PMID- 25367210
TI  - Immunoblot for the detection of Ascaris suum-specific antibodies in patients with
      visceral larva migrans (VLM) syndrome.
AB  - Visceral larva migrans (VLM) syndrome caused by Toxocara canis larvae was first
      described in the 1950s. The role of other nematode larvae, i.e. the pig roundworm
      Ascaris suum as a causative agent of visceral larva migrans-associated symptoms
      like general malaise, cough, liver dysfunction, hypereosinophilia with
      hepatomegaly and/or pneumonia, was discussed controversially during the last
      decades. Recent serological screening studies for specific A. suum antibodies
      carried out in the Netherlands and Sweden yielded remarkable high
      seroprevalences, while a number of case reports from Japan report pulmonal,
      hepatic and cerebral symptoms caused by A. suum larvae after ingestion of
      infected raw meat (liver) or contaminated vegetables. We present here a sensitive
      and specific larval excretory-secretory (E/S) antigen-based immunoblot (As-IB)
      for the serodiagnosis of A. suum-infected patients suffering from symptoms
      associated to the VLM syndrome. In total, 34 sera from patients with
      hypereosinophilia and other clinical symptoms associated to the VLM syndrome
      tested negative for Toxocara sp. antibodies but positive in our newly established
      As-IB, 30 sera from healthy volunteers, 53 sera from patients with clinically and
      serologically confirmed toxocarosis and other helminthoses as well as 3 sera from
      patients with intestinal ascariosis due to Ascaris lumbricoides were included in
      the study. When evaluated with 30 sera from healthy volunteers and 53 sera from
      patients suffering from different helminthoses, the calculated specificity of our
      new As-IB is 95%. Problems hampering the establishment of simple serological
      screening tests for specific A. suum antibodies, like extensive antigenic
      similarities between the nematodes Ascaris and Toxocara or the absence of
      suitable experimental animals, are discussed. We assume that specific serological
      testing for antibodies of A. suum is very important for the treatment of
      individual patients on one hand and seroepidemiological investigations will help
      to clarify routes of transmission on the other hand. Further studies will be
      necessary to learn more about the extent of A. suum as a causative agent of the
      VLM syndrome and the role of pigs and their manure as the main source of human
      Ascaris infections in Austria and other industrialized countries.

PMID- 25367211
TI  - Morphology, phylogeny and seasonal prevalence of Ceratomyxa arabica n. sp.
      (Myxozoa: Myxosporea) infecting the gallbladder of Acanthopagrus bifasciatus
      (Pisces: Sparidae) from the Arabian Gulf, Saudi Arabia.
AB  - A new myxozoan species was recovered from the gallbladder of Acanthopagrus
      bifasciatus from the Arabian Gulf in Saudi Arabia. The overall prevalence of
      infection was 28.6 % (32/112), with the highest prevalence 42.9 % (12/28) in
      winter and 10.7 % (3/28) as the lowest in autumn. The new species is described
      using its morphological characteristics and small subunit (SSU) rDNA. Spores of
      Ceratomyxa arabica n. sp. are stubby-shaped with unequal shell valves, 8 (7-9)
      MUm in length * 12 (10-14) MUm in thickness. Polar capsules are sub-spherical,
      unequal, 3 (2.5-3.5) * 2 (1.5-2.5) MUm. The polar filament has three turns and is
      slightly slanted towards the longitudinal axis of the capsules. The small subunit
      rDNA (SSU rDNA) sequence confirms that the present species is a member of the
      genus Ceratomyxa, being most closely related to Ceratomyxa cardinalis with a
      sequence similarity of 97.77 %.

PMID- 25367213
TI  - Magnetized silane-coupling agent KH-570 based solid-phase extraction followed by
      gas chromatography-flame ionization detection to determine venlafaxine in human
      hair and aqueous environmental samples.
AB  - In the present study, a novel adsorbent, Fe3O4 magnetic nanoparticles (MNPs)
      functionalized by silane-coupling agent KH-570, was successfully synthesized. The
      prepared MNPs were characterized by Fourier-transform infrared spectroscopy and
      transmission electron microscopy. It was applied as functionalized magnetic nano
      adsorbent for magnetic solid-phase extraction of trace levels of venlafaxine
      using gas chromatography with flame ionization detector. This method was
      developed and optimized for use in analysis of venlafaxine in human hair and
      aqueous environmental samples. The main factors influencing the extraction
      efficiency including pH of sample, amount of the MNPs, adsorption time, volume of
      sample, and desorption conditions such as volume of solvent and desorption time
      were studied and optimized. Under the optimized experimental conditions, good
      linearity was observed in the range of 1-1,000 ug L(-1) for aqueous environmental
      samples with correlation coefficients (R (2)) 0.996. The limits of detection and
      quantification were 0.1 and 0.5 MUg L(-1), respectively. Good reproducibility
      with the relative standard deviations (n = 5) 3.21 % was obtained. The developed
      method was successfully applied to the extraction of venlafaxine from spiked
      human hair, river water, and surface water samples and the relative recoveries of
      89.36, 93.43, and 94.99 % were obtained, respectively. The results indicated that
      Fe3O4/KH-570 MNPs have a satisfying extraction efficiency and can be served as a
      sensitive, inexpensive, and reliable method for analysis of antidepressant drugs
      such as venlafaxine in biological and aqueous environmental samples.

PMID- 25367212
TI  - Simultaneous infection by four feline lungworm species and implications for the
      diagnosis.
AB  - Besides Aelurostrongylus abstrusus, other parasites belonging to the superfamily
      Metastrongyloidea, namely Oslerus rostratus, Troglostrongylus brevior and to the
      family Trichuridae, i.e. Eucoleus aerophilus (syn. Capillaria aerophila), have
      also been reported as agents of respiratory infection in domestic cats. A case of
      simultaneous infection by four feline lungworm species in Sardinia is herein
      described. An adult female cat (Felis silvestris catus), road-killed in the
      southeast part of Sardinia (municipality of Villacidro, province of Cagliari),
      Italy, was referred to the Laboratory of Parasitology of the Veterinary Teaching
      Hospital in Sassari. At necropsy, the lungs were examined and dissected under a
      stereomicroscope for the presence of parasites, and first-stage larvae (L1) of
      broncho-pulmonary nematodes were searched for in a faecal sample using the
      Baermann method. Parasites collected in the lungs were morphologically identified
      as A. abstrusus, E. aerophilus, and O. rostratus. In addition to the above
      species, L1s of Troglostrongylus spp. were detected at coproscopy but no adult
      specimen was found in the lungs. The morphological identification was confirmed
      by the molecular amplification and sequencing of cox1 mitochondrial gene, 18S and
      ITS2 ribosomal DNA. This finding stands as the first simultaneous infection by
      four feline lungworm species in the same animal, and as the first report of O.
      rostratus and E. aerophilus in Sardinia. 

PMID- 25367214
TI  - Bismuth(III) volatilization and immobilization by filamentous fungus Aspergillus
      clavatus during aerobic incubation.
AB  - As with many metals, bismuth can be accumulated or transformed by microorganisms.
      These interactions affect microbial consortia and bismuth environmental
      behaviour, mobility, and toxicity. Recent research focused specifically on
      bismuth anaerobic transformation by bacteria and archaea has inspired the
      evaluation of the mutual interactions between bismuth and filamentous fungi as
      presented in this article. The Aspergillus clavatus fungus proved resistant to
      adverse effects from bismuth contamination in culture medium with up to a
      concentration of 195 umol L(-1) during static 15- and 30-day cultivation. The
      examined resistance mechanism includes biosorption to the fungal surface and
      biovolatilization. Pelletized fungal biomass has shown high affinity for
      dissolved bismuth(III). Bismuth biosorption was rapid, reaching equilibrium after
      50 min with a 0.35 mmol g(-1) maximum sorption capacity as calculated from the
      Langmuir isotherm. A. clavatus accumulated <=70 umol g(-1) of bismuth after 30
      days. Preceding isotherm study implications that most accumulated bismuth binds
      to cell wall suggests that biosorption is the main detoxification mechanism.
      Accumulated bismuth was also partly volatilized (<=1 umol) or sequestrated in the
      cytosol or vacuoles. Concurrently, <=1.6 umol of bismuth remaining in solution
      was precipitated by fungal activity. These observations indicate that complex
      mutual interactions between bismuth and filamentous fungi are environmentally
      significant regarding bismuth mobility and transformation.

PMID- 25367215
TI  - Lipopolysaccharide enhances OSCC migration by promoting epithelial-mesenchymal
      transition.
AB  - BACKGROUND: This study was performed to examine whether lipopolysaccharide can
      influence cell migration and epithelial-mesenchymal transition of oral squamous
      cell carcinoma. METHODS: Three oral squamous cell carcinoma cell lines (HSC3,
      CAL27, and SCC4) were obtained for the study. TLR4 expression in three cell lines
      was analyzed by Q-PCR and Western blot. After cells treated with LPS, cell
      migration was analyzed by wound-healing and chemotaxis cell migration assay.
      Changes of E-cadherin and vimentin expression were tested by Western blot and
      immunofluorescence staining. To examine NF-kappaB activation, NF-kappaB nuclear
      translocation was investigated. RESULTS: TLR4 was expressed in all three cell
      lines and was highest in HSC3 while lowest in SCC4. TLR4 ligand
      lipopolysaccharide accelerated wound healing and enhanced cell migration. Also,
      it stimulated epithelial-mesenchymal transition demonstrated by decreased E
      cadherin and increased vimentin expression. Lipopolysaccharide also provoked NF
      kappaB nuclear translocation. Either TLR4 or NF-kappaB blocking reverted these
      effects. CONCLUSIONS: Lipopolysaccharide can induce TLR4-mediated epithelial
      mesenchymal transition and cell migration in oral squamous cell carcinoma. These
      responses could further affect tumor progressing by inducing tumor cell
      metastasis.

PMID- 25367216
TI  - Fluidic switching in nanochannels for the control of Inchworm: a synthetic
      biomolecular motor with a power stroke.
AB  - Synthetic molecular motors typically take nanometer-scale steps through
      rectification of thermal motion. Here we propose Inchworm, a DNA-based motor that
      employs a pronounced power stroke to take micrometer-scale steps on a time scale
      of seconds, and we design, fabricate, and analyze the nanofluidic device needed
      to operate the motor. Inchworm is a kbp-long, double-stranded DNA confined inside
      a nanochannel in a stretched configuration. Motor stepping is achieved through
      externally controlled changes in salt concentration (changing the DNA's
      extension), coordinated with ligand-gated binding of the DNA's ends to the
      functionalized nanochannel surface. Brownian dynamics simulations predict that
      Inchworm's stall force is determined by its entropic spring constant and is ~ 0.1
      pN. Operation of the motor requires periodic cycling of four different buffers
      surrounding the DNA inside a nanochannel, while keeping constant the hydrodynamic
      load force on the DNA. We present a two-layer fluidic device incorporating 100 nm
      radius nanochannels that are connected through a few-nm-wide slit to a
      microfluidic system used for in situ buffer exchanges, either diffusionally (zero
      flow) or with controlled hydrodynamic flow. Combining experiment with finite
      element modeling, we demonstrate the device's key performance features and
      experimentally establish achievable Inchworm stepping times of the order of
      seconds or faster.

PMID- 25367217
TI  - The dynamic dielectric at a brain functional site and an EM wave approach to
      functional brain imaging.
AB  - Functional brain imaging has tremendous applications. The existing methods for
      functional brain imaging include functional Magnetic Resonant Imaging (fMRI),
      scalp electroencephalography (EEG), implanted EEG, magnetoencephalography (MEG)
      and Positron Emission Tomography (PET), which have been widely and successfully
      applied to various brain imaging studies. To develop a new method for functional
      brain imaging, here we show that the dielectric at a brain functional site has a
      dynamic nature, varying with local neuronal activation as the permittivity of the
      dielectric varies with the ion concentration of the extracellular fluid
      surrounding neurons in activation. Therefore, the neuronal activation can be
      sensed by a radiofrequency (RF) electromagnetic (EM) wave propagating through the
      site as the phase change of the EM wave varies with the permittivity. Such a
      dynamic nature of the dielectric at a brain functional site provides the basis
      for an RF EM wave approach to detecting and imaging neuronal activation at brain
      functional sites, leading to an RF EM wave approach to functional brain imaging. 

PMID- 25367218
TI  - Hepatitis C transmission from viremic donors in hematopoietic stem cell
      transplant.
AB  - Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell
      transplant (HSCT) occurs frequently from HCV viremic donors and causes
      complications. Here, we report the outcomes of 3 cases from our 265 allogeneic
      HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission
      was noted in 1 recipient by pretreatment of the donor with
      peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell
      harvest. This case stressed the important role of effective antiviral therapy and
      HCV RNA seronegativity before cell harvest for prevention of HCV transmission in
      HSCT. 

PMID- 25367219
TI  - Mapping epistatic quantitative trait loci.
AB  - BACKGROUND: How to map quantitative trait loci (QTL) with epistasis efficiently
      and reliably has been a persistent problem for QTL mapping analysis. There are a
      number of difficulties for studying epistatic QTL. Linkage can impose a
      significant challenge for finding epistatic QTL reliably. If multiple QTL are in
      linkage and have interactions, searching for QTL can become a very delicate
      issue. A commonly used strategy that performs a two-dimensional genome scan to
      search for a pair of QTL with epistasis can suffer from low statistical power and
      also may lead to false identification due to complex linkage disequilibrium and
      interaction patterns. RESULTS: To tackle the problem of complex interaction of
      multiple QTL with linkage, we developed a three-stage search strategy. In the
      first stage, main effect QTL are searched and mapped. In the second stage,
      epistatic QTL that interact significantly with other identified QTL are searched.
      In the third stage, new epistatic QTL are searched in pairs. This strategy is
      based on the consideration that most genetic variance is due to the main effects
      of QTL. Thus by first mapping those main-effect QTL, the statistical power for
      the second and third stages of analysis for mapping epistatic QTL can be
      maximized. The search for main effect QTL is robust and does not bias the search
      for epistatic QTL due to a genetic property associated with the orthogonal
      genetic model that the additive and additive by additive variances are
      independent despite of linkage. The model search criterion is empirically and
      dynamically evaluated by using a score-statistic based resampling procedure. We
      demonstrate through simulations that the method has good power and low false
      positive in the identification of QTL and epistasis. CONCLUSION: This method
      provides an effective and powerful solution to map multiple QTL with complex
      epistatic pattern. The method has been implemented in the user-friendly computer
      software Windows QTL Cartographer. This will greatly facilitate the application
      of the method for QTL mapping data analysis.

PMID- 25367220
TI  - A phosphoproteomic screen demonstrates differential dependence on HER3 for MAP
      kinase pathway activation by distinct PIK3CA mutations.
AB  - The PIK3CA gene encodes for the p110 alpha isoform of PI3 kinase and is one of
      the most frequently mutated oncogenes in human cancers. However, the mechanisms
      by which PIK3CA mutations activate cell signaling are not fully understood. Here
      we used a phosphoproteomic approach to compare differential phosphorylation
      patterns between human breast epithelial cells and two isogenic somatic cell
      knock in derivatives, each harboring a distinct PIK3CA mutation. We demonstrated
      differential phosphorylation patterns between isogenic cell lines containing a
      PIK3CA helical domain mutation (E545K) compared to cells with a PIK3CA kinase
      domain mutation (H1047R). In particular, the receptor tyrosine kinase, HER3,
      showed increased phosphorylation at tyrosine 1328 in H1047R cells versus E545K
      cells. Genetic studies using shRNA demonstrated that H1047R cells have a profound
      decrease in growth factor independent proliferation upon HER3 knock down, but
      this effect was attenuated in E545K cells. In addition, HER3 knock down led to
      reductions in both PI3 kinase and MAP kinase pathway activation in H1047R cells,
      but in E545K cells only PI3 kinase pathway diminution was observed. These studies
      demonstrate the power of using paired isogenic cell lines for proteomic analysis
      to gain new insights into oncogenic signal transduction pathways. 

PMID- 25367221
TI  - The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis.
AB  - Primary cilia are microtubule-based organelles that protrude from polarized
      epithelial cells. Although many structural and trafficking molecules that
      regulate ciliogenesis have been discovered, signalling proteins are not well
      defined. Here we show that the MST1/2-SAV1 complex, a core component of the Hippo
      pathway, promotes ciliogenesis. MST1 is activated during ciliogenesis and
      localizes to the basal body of cilia. Depletion of MST1/2 or SAV1 impairs
      ciliogenesis in cultured cells and induces ciliopathy phenotypes in zebrafish.
      MST1/2-SAV1 regulates ciliogenesis through two independent mechanisms: MST1/2
      binds and phosphorylates Aurora kinase A (AURKA), leading to dissociation of the
      AURKA/HDAC6 cilia-disassembly complex; and MST1/2-SAV1 associates with the NPHP
      transition-zone complex, promoting ciliary localization of multiple ciliary
      cargoes. Our results suggest that components of the Hippo pathway contribute to
      establish a polarized cell structure in addition to regulating proliferation. 

PMID- 25367222
TI  - Mirror therapy combined with biofeedback functional electrical stimulation for
      motor recovery of upper extremities after stroke: a pilot randomized controlled
      trial.
AB  - The objective of this study was to evaluate the effects of mirror therapy in
      combination with biofeedback functional electrical stimulation (BF-FES) on motor
      recovery of the upper extremities after stroke. Twenty-nine patients who suffered
      a stroke > 6 months prior participated in this study and were randomly allocated
      to three groups. The BF-FES + mirror therapy and FES + mirror therapy groups
      practiced training for 5 * 30 min sessions over a 4-week period. The control
      group received a conventional physical therapy program. The following clinical
      tools were used to assess motor recovery of the upper extremities: electrical
      muscle tester, electrogoniometer, dual-inclinometer, electrodynamometer, the Box
      and Block Test (BBT) and Jabsen Taylor Hand Function Test (JHFT), the Functional
      Independence Measure, the Modified Ashworth Scale, and the Stroke Specific
      Quality of Life (SSQOL) assessment. The BF-FES + mirror therapy group showed
      significant improvement in wrist extension as revealed by the Manual Muscle Test
      and Range of Motion (p < 0.05). The BF-FES + mirror therapy group showed
      significant improvement in the BBT, JTHT, and SSQOL compared with the FES +
      mirror therapy group and control group (p < 0.05). We found that BF-FES + mirror
      therapy induced motor recovery and improved quality of life. These results
      suggest that mirror therapy, in combination with BF-FES, is feasible and
      effective for motor recovery of the upper extremities after stroke.

PMID- 25367223
TI  - Functional implications of variation in tooth spacing and crown size in
      pinnipedimorpha (mammalia: carnivora).
AB  - Pinnipeds (seals, sea lions, and walruses) show variation in tooth morphology
      that relates to ecology. However, crown size and spacing are two aspects of
      morphology that have not been quantified in prior studies. We measured these
      characters for nearly all extant pinnipeds and three fossil taxa and then
      determined the principal sources of variation in tooth size and spacing using
      principal components (PCAs) and hierarchical cluster analysis (HCA). PCA and HCA
      showed that species sorted into three groups: taxa with small crowns and large
      diastemata, taxa with large crowns and small diastemata, and taxa that fell
      between these two extremes. We then performed discriminant function analysis
      (DFA) to determine if tooth morphology correlated with foraging strategy or diet.
      DFA results indicated weak correlation with diet, and stronger correlation with
      prey capture strategies. Tooth size and spacing were most strongly correlated
      with the importance of teeth in prey acquisition, with tooth size decreasing and
      tooth spacing increasing as teeth become less necessary in capturing food items.
      Taxa which relied on teeth for filtering prey from the water column or processing
      larger or tougher food items generally had larger crowns and smaller tooth
      spacing then taxa which swallowed prey whole. We found the fossil taxa
      Desmatophoca and Enaliarctos were most similar in tooth morphology to extant
      otariids, suggesting that both taxa were generalist feeders. This study
      established the relationship between tooth size and feeding behavior, and
      provides a new tool to explore the paleoecology of fossil pinnipeds and other
      aquatic tetrapods.

PMID- 25367225
TI  - Quasi-2D Cu2 S crystals on graphene: in-situ growth and ab-initio calculations.
AB  - Two-dimensional crystals of beta-copper sulfide are synthesized in an in-situ
      electron microscopy experiment. Copper crystals are deposited on an amorphous
      carbon film containing sulfur. The carbon film graphitizes upon heating and
      electron irradiation and allows the reaction of Cu and S towards two-dimensional
      Cu(2) S crystals. These are energetically favourable and bonded via van der Waals
      interactions to the graphitic substrate.

PMID- 25367224
TI  - The rise of medical training in Portuguese speaking African countries.
AB  - BACKGROUND: Medical training has shown to be strategic for strengthening health
      systems, especially in those countries identified to have critical shortage of
      human resources for health. In the past few years, several studies have been
      conducted to characterize and identify major challenges faced by medical schools
      worldwide, and particularly in Africa. Nevertheless, none has previously
      addressed medical training issues in Portuguese Speaking African Countries
      (PSAC). The aim of this study was to establish baseline knowledge of the PSAC's
      medical schools in terms of creation and ownership, programmes offered,
      applicants and registered students, barriers to increased intake of students,
      teaching workforce and available resources. METHODS: A quantitative,
      observational, multicentric, cross-sectional study of all medical schools active
      in 2012 in the PSAC. An adapted version of the questionnaires developed by Chen
      et al. (2012) was sent to all medical schools electronically. Data were analyzed
      using descriptive statistics. RESULTS: A total of nine medical schools answered
      the questionnaire (three from Angola, two from Guinea Bissau and four from
      Mozambique). Since 2006 an effort has been made to increase the number of medical
      trainees. Besides the medical degree offered by all schools, some offered other
      undergraduate and postgraduate training programmes. The number of applicants to
      medical schools largely outnumbers the available vacancies in all countries but
      insufficient infrastructures and lack of teaching personnel are important
      constraints to increase vacancies. The teaching personnel are mainly trained
      abroad, employed part-time by the medical school and do not have a PhD
      qualification. CONCLUSION: Governments in the PSAC have significantly invested in
      training to address medical shortages. However, medical schools are still
      struggling to give an adequate and effective response. Developing a local
      postgraduate training capacity for doctors might be an important strategy to help
      retain medical doctors in the home country and develop local faculty capacity.

PMID- 25367226
TI  - How do patients with previous RV pacing respond to upgrading to CRT? Important
      messages for pacemaker and ICD follow-up.

PMID- 25367227
TI  - Usefulness of near-infrared spectroscopy in thrombectomy monitoring.
AB  - Monitoring recanalization and reperfusion during acute ischemic stroke is a
      challenge for therapeutic assessment. Near-infrared spectroscopy (NIRS) allows
      continuous monitoring of the brain regional saturation of oxygen (rSO2). We
      sought to evaluated rSO2 variation during mechanical thrombectomy during acute
      ischemic stroke. Three patients admitted for middle cerebral artery occlusion
      were continuously monitored during mechanical thrombectomy (rSO2 in the infarcted
      and non-infarcted side and interhemispheric difference). The procedure was a
      success in two of them and failed in the third. At the beginning, rSO2 was lower
      in the infarcted side and interhemispheric difference was more than 5%. When the
      procedure succeeded, rSO2 in the infarcted side rise (about 10%) and
      interhemisperic difference decrease (about 7%). When the procedure failed, rSO2
      was the same at the beginning and at the end. NIRS may be useful to monitor
      recanalization during management of acute ischemic stroke.

PMID- 25367228
TI  - Diversity and relative abundance of the bacterial pathogen, Flavobacterium spp.,
      infecting reproductive ecotypes of kokanee salmon.
AB  - BACKGROUND: Understanding the distribution and abundance of pathogens can provide
      insight into the evolution and ecology of their host species. Previous research
      in kokanee, the freshwater form of sockeye salmon (Oncorhynchus nerka), found
      evidence that populations spawning in streams may experience a greater pathogen
      load compared with populations that spawn on beaches. In this study we tested for
      differences in the abundance and diversity of the gram-negative bacteria,
      Flavobacterium spp., infecting tissues of kokanee in both of these spawning
      habitats (streams and beaches). Molecular assays were carried out using primers
      designed to amplify a ~200 nucleotide region of the gene encoding the ATP
      synthase alpha subunit (AtpA) within the genus Flavobacterium. Using a
      combination of DNA sequencing and quantitative PCR (qPCR) we compared the
      diversity and relative abundance of Flavobacterium AtpA amplicons present in DNA
      extracted from tissue samples of kokanee collected from each spawning habitat.
      RESULTS: We identified 10 Flavobacterium AtpA haplotypes among the tissues of
      stream-spawning kokanee and seven haplotypes among the tissues of beach-spawning
      kokanee, with only two haplotypes shared between spawning habitats. Haplotypes
      occurring in the same clade as F. psychrophilum were the most prevalent (92% of
      all reads, 60% of all haplotypes), and occurred in kokanee from both spawning
      habitats (streams and beaches). Subsequent qPCR assays did not find any
      significant difference in the relative abundance of Flavobacterium AtpA amplicons
      between samples from the different spawning habitats. CONCLUSIONS: We confirmed
      the presence of Flavobacterium spp. in both spawning habitats and found weak
      evidence for increased Flavobacterium diversity in kokanee sampled from stream
      spawning sites. However, the quantity of Flavobacterium DNA did not differ
      between spawning habitats. We recommend further study aimed at quantifying
      pathogen diversity and abundance in population-level samples of kokanee combined
      with environmental sampling to better understand the ecology of pathogen
      infection in this species.

PMID- 25367229
TI  - Collection of analytes from microneedle patches.
AB  - Clinical medicine and public health would benefit from simplified acquisition of
      biological samples from patients that can be easily obtained at point of care, in
      the field, and by patients themselves. Microneedle patches are designed to serve
      this need by collecting dermal interstitial fluid containing biomarkers without
      the dangers, pain, or expertise needed to collect blood. This study presents
      novel methods to collect biomarker analytes from microneedle patches for analysis
      by integration into conventional analytical laboratory microtubes and
      microplates. Microneedle patches were made out of cross-linked hydrogel composed
      of poly(methyl vinyl ether-alt-maleic acid) and poly(ethylene glycol) prepared by
      micromolding. Microneedle patches were shown to swell with water up to 50-fold in
      volume, depending on degree of polymer cross-linking, and to collect interstitial
      fluid from the skin of rats. To collect analytes from microneedle patches, the
      patches were mounted within the cap of microcentrifuge tubes or formed the top of
      V-bottom multiwell microplates, and fluid was collected in the bottom of the
      tubes under gentle centrifugation. In another method, microneedle patches were
      attached to form the bottom of multiwell microplates, thereby enabling in situ
      analysis. The simplicity of biological sample acquisition using microneedle
      patches coupled with the simplicity of analyte collection from microneedles
      patches integrated into conventional analytical equipment could broaden the reach
      of future screening, diagnosis, and monitoring of biomarkers in healthcare and
      environmental/workplace settings.

PMID- 25367230
TI  - [Check-ups and screening for young people: what is reasonable with respect to
      psychiatric disorders?].
AB  - BACKGROUND: Severe mental illnesses become manifested early in life. First
      episodes are suffered in young adulthood at the latest and early symptoms and
      signs are often already reported in childhood and adolescence. Therefore, it is
      exactly these adolescents and young adults who have to be reached to detect signs
      early. OBJECTIVES: In this article the check-ups and screening procedures
      routinely offered for this target group as well as the role of groups of persons
      who accompany young people in a variety of contexts are illustrated. Potential
      extensions with elements and structures for the early recognition of severe
      mental illnesses are outlined. RESULTS: With the integration of psychiatric
      peculiarities and drug consumption into the diagnostic battery of the first
      adolescence healthcare examination (Jugendgesundheitsuntersuchung J1), the often
      already established familiarity of young persons and the waiving of costs by the
      health insurances, the J1 seems to be well-suited to provide a rough screening
      for precursor stages and risk factors for the development of severe mental
      illnesses and for the detection of a suspected manifest mental disorder. The
      primary role of most persons working with young people is to be a contact partner
      and to help transferring the person to the adequate service. Several early
      recognition centers were founded in Germany to offer low-threshold contact
      services in the view of existing barriers to care for help-seeking young persons
      and to provide the complex diagnostics. CONCLUSIONS: The adolescence healthcare
      examinations can be a useful element for early detection of mental disorders and
      damaging behavior if the utilization rate is high and actions taken in case of
      suspected beginning disorder/damaging behavior are evaluated. To date, screening
      instruments for psychiatric disorders should not be used in wide population
      classes without group-specific targets and without direct contact between
      therapists and patients. Already established preventive services and initiatives
      should be interlinked. The health effects of the actions have to be analyzed.

PMID- 25367231
TI  - [Sinus thrombosis in a 15-year-old girl : An interdisciplinary case].

PMID- 25367232
TI  - Numerical evaluation of myofiber orientation and transmural contractile strength
      on left ventricular function.
AB  - The left ventricle (LV) of the heart is composed of a complex organization of
      cardiac muscle fibers, which contract to generate force and pump blood into the
      body. It has been shown that both the orientation and contractile strength of
      these myofibers vary across the ventricular wall. The hypothesis of the current
      study is that the transmural distributions of myofiber orientation and
      contractile strength interdependently impact LV pump function. In order to
      quantify these interactions a finite element (FE) model of the LV was generated,
      which incorporated transmural variations. The influences of myofiber orientation
      and contractile strength on the Starling relationship and the end-systolic (ES)
      apex twist of the LV were assessed. The results suggest that reductions in
      contractile strength within a specific transmural layer amplified the effects of
      altered myofiber orientation in the same layer, causing greater changes in stroke
      volume (SV). Furthermore, when the epicardial myofibers contracted the strongest,
      the twist of the LV apex was greatest, regardless of myofiber orientation. These
      results demonstrate the important role of transmural distribution of myocardial
      contractile strength and its interplay with myofiber orientation. The coupling
      between these two physiologic parameters could play a critical role in the
      progression of heart failure. 

PMID- 25367233
TI  - Coronary artery bypass grafting in a patient with myasthenia gravis.
AB  - A 70-year-old male patient with myasthenia gravis required coronary artery bypass
      grafting due to triple-vessel disease. The anesthetic management was performed
      with general anesthesia using reduced doses of muscle relaxants. He was extubated
      four hours after surgery and the postoperative course was uneventful. Coronary
      artery bypass surgery in myasthenic patients can be challenging to
      anesthesiologists and cardiac surgeons. In this rare condition, a meticulous
      assessment of the patient's neurologic and cardiac status, and careful
      perioperative anesthetic management were needed in order to avoid life
      threatening complications in both intraoperative and postoperative periods. 

PMID- 25367234
TI  - Transcatheter aortic valve implantation via right carotid artery route for severe
      aortic regurgitation management in a patient with chronic operated type A aortic
      dissection.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) technique is now
      widely accepted as an alternative for the treatment of very high-risk patients in
      cases of aortic stenosis. However, use of this technique in cases of pure native
      aortic regurgitation (AR) remains discussed. CASE REPORT: We report the case of a
      68-year-old patient with severe AR referred to our hospital 10 years after a
      supracoronary ascending aorta replacement surgery for acute type A aortic
      dissection. Because of respiratory contraindication to redo sternotomy, we
      treated this patient with the implantation of a CoreValve prosthesis inserted via
      right carotid access. We discuss the TAVI strategy in the case of severe AR and
      the possibility to use alternative vascular access. CONCLUSION: In very high-risk
      patients, TAVI can be discussed and considered as an alternative treatment for
      severe AR, with right carotid access proven as feasible.

PMID- 25367235
TI  - The effect of lidocaine and amiodarone on prevention of ventricular fibrillation
      in patients undergoing coronary artery bypass grafting.
AB  - OBJECTIVE: Ventricular fibrillation is common after aortic declamping in patients
      undergoing open heart surgery. This situation has a negative impact on morbidity
      and mortality. The aim of this prospective study was to compare the effect of
      administering lidocaine versus amiodarone before aortic declamping during
      elective coronary bypass grafting, paying close attention to when the initial
      effect of amiodarone sets in. METHODS: In this double blind, prospective,
      randomized, controlled study, 86 patients who were candidates for elective
      coronary artery bypass grafting were recruited into three groups: group lidocaine
      (group L, n=29); group amiodarone (group A, n=27); and group placebo (group P,
      n=30). Group L patients received 1.5 mg/kg of lidocaine 2 minutes before aortic
      declamping and group A patients received 300 mg of amiodarone intravenously 15
      minutes before release of the aortic cross clamp. The primary endpoints were the
      incidence of ventricular fibrillation and the number of shocks required to
      terminate ventricular fibrillation. RESULTS: The frequency of ventricular
      fibrillation occurrence was significantly higher in group P (70%) when compared
      with group A (37%) and group L (38%) (P=.017). There was no statistically
      significant difference between the amiodarone and the lidocaine groups regarding
      ventricular fibrillation. However, when ventricular fibrillation occurred, the
      percentage of patients requiring electrical defibrillation was significantly
      higher in both group L and group P when compared with group A (P=.023).
      CONCLUSION: We suggest that during coronary arterial bypass surgery,
      administration of an amiodarone regime before release of the aortic cross clamp,
      paying particular attention to the start of the initial effect of amiodarone, is
      no more effective than lidocaine for prevention from arrhythmia; however,
      amiodarone reduces the need for electrical defibrillation.

PMID- 25367236
TI  - A rare case of ALCAPA and rheumatic mitral valve regurgitation in an adult
      patient.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital coronary artery defect leading to sudden cardiac death.
      Diagnosis is made after the onset of symptoms, mainly in the pediatric
      population. We describe an uncommon presentation of ALCAPA and rheumatic mitral
      valve regurgitation, diagnosed by a coronary 64-CT scan performed before a
      planned mitral valve repair operation. 

PMID- 25367237
TI  - Diagnosis of coronary affection in patients with AADA and treatment of
      postcardiotomy myocardial failure using extracorporeal life support (ECLS).
AB  - BACKGROUND: Myocardial ischemia due to concomitant coronary artery disease (CAD)
      or coronary dissection in patients with acute aortic dissection type Stanford A
      (AADA) is associated with myocardial failure and poor outcomes. Preoperative
      coronary angiography in this group of patients is still debated. The use of CT
      scan to diagnose coronary affection along with the establishment of high-pitched
      dual-spiral CT protocols are essential for improving outcomes. METHODS: We
      retrospectively analyzed six AADA patients with heart failure who were treated
      using extracorporeal life support (ECLS). Options for diagnosing coronary
      affection and different therapeutic strategies for postcardiotomy cardiogenic
      shock in this patient cohort are discussed. RESULTS: Retrospective review of CT
      images showed coronary abnormalities in 83% (n=5). Four patients (67%) underwent
      unplanned coronary artery bypass grafting (CABG). ECLS was instituted in 67%
      (n=4) due to left heart failure and in 33% (n=2) due to right heart failure.
      Thirty day mortality was 67% (n=4). The two patients that received ECLS for right
      ventricular support survived and both had undergone CABG. CONCLUSION: Besides
      preoperative evaluation of the extent of the dissection, focus on coronary
      affection in CT-scans helps to triage the operative procedure. Hybrid operating
      rooms allow for immediate interventional and/or surgical treatment and enable for
      immediate control of revascularization results. The use of ECLS over other types
      of ventricular support systems may allow for myocardial recovery in selected
      cases.

PMID- 25367238
TI  - A case of Heyde syndrome: resolution following aortic valve replacement.
AB  - Heyde syndrome is a triad of aortic stenosis, acquired coagulopathy, and anemia
      due to bleeding from intestinal angiodysplasia. Here we describe a case of this
      syndrome. An 80-year-old woman with severe aortic stenosis was referred to our
      department for an aortic valve replacement. She suffered from recurrent iron
      deficiency anemia and required transfusions every 2 weeks. Gastroscopy and
      colonoscopy were normal with the exception of angiodysplasia without bleeding in
      the cecum. After aortic valve replacement her anemia was resolved. She was
      discharged on postoperative day 22. No transfusions were needed after the
      procedure. To date, her hemoglobin has remained stable at >10 mg/dL. 

PMID- 25367239
TI  - Improved angiographic findings of superficial femoral artery after verapamil
      injection into the reperfusion cannula of a patient on peripheral venoarterial
      ECMO.
AB  - Limb ischemia is a complication that can occur in patients requiring
      percutaneously placed venoarterial extracorporeal membrane oxygenation (ECMO).
      One method used to prevent limb ischemia is the placement of an antegrade
      catheter into the superficial femoral artery. We describe a case is which the
      angiographic findings of the superficial femoral artery were improved by the
      injection of verapamil in a patient with limb ischemia. 

PMID- 25367240
TI  - Effects of the AT1 receptor blocker candesartan on myocardial
      ischemia/reperfusion in isolated rat hearts.
AB  - BACKGROUND: We sought to investigate the effects of the angiotension II receptor
      blocker candesartan on ischemia-reperfusion injury using a cardioplegia arrested
      isolated rat heart model. METHODS: Ischemia-reperfusion injury was induced in
      isolated rat hearts with 40 minutes of global ischemia followed by a 30-minute
      reperfusion protocol. Throughout the experiment, constant pressure perfusion was
      achieved using a Langendorff apparatus. Cardioplegic solution alone, and in
      combination with candesartan, was administered before ischemia and 20 minutes
      after ischemia. Post-ischemic recovery of contractile function, left ventricular
      developed pressure, left ventricular end-diastolic pressure and contraction and
      relaxation rates were evaluated. RESULTS: In the control group, left ventricular
      developed pressure, rate pressure product, contraction and relaxation rates and
      coronary flow significantly decreased but coronary resistance increased following
      reperfusion. With the administration of candesartan alone, parameters did not
      differ compared to controls. Contractile parameters improved in the group that
      received candesartan in combination with the cardioplegia compared to the group
      that received cardioplegia alone; however, the difference between these two
      groups was insignificant. CONCLUSION: In this study, the addition of candesartan
      to a cardioplegic arrest protocol routinely performed during cardiac surgery did
      not provide a significant advantage in protection against ischemia-reperfusion
      injury compared with the administration of cardioplegic solution alone.

PMID- 25367241
TI  - Modified septal myectomy using a curved knife for left ventricular septal
      hypertrophy.
AB  - An 86-year-old woman presented with chest pain and discomfort. Echocardiography
      revealed severe aortic valve stenosis and asymmetric septal hypertrophy. Aortic
      valve replacement and myectomy were performed using a curved knife. The blade was
      U-shaped in cross-section, and was curved upward along the long axis.
      Hypertrophic septal myocardium was removed along the long axis of the left
      ventricle (LV), and a groove for blood flow was constructed. The patient was
      discharged uneventfully without recurrence of her chest discomfort. Our result
      suggested that a curved knife is a reasonable option for transaortic septal
      myectomy in patients with obstructive LV hypertrophy. 

PMID- 25367242
TI  - Effects of off-pump versus on-pump coronary artery bypass grafting: apoptosis,
      inflammation, and oxidative stress.
AB  - BACKGROUND: It has been suggested that off-pump coronary artery bypass grafting
      (CABG) surgery reduces myocardial ischemia-reperfusion injury, postoperative
      systemic inflammatory response, and oxidative stress. The aim of this study was
      to measure serum malondialdehyde (MDA), high-sensitivity C-reactive protein (hs
      CRP), M30, and M65 levels and to investigate the relationship between M30 levels
      and oxidative stress and inflammation in patients undergoing on-and off-pump CABG
      surgery. METHODS: Fifty patients were randomly assigned to on-pump or off-pump
      CABG surgery (25 patients off-pump and 25 on-pump CABG surgery), and blood
      samples were collected prior to surgery, and 30 minutes, 60 minutes, 6 hours, and
      24 hours after CABG surgery. RESULTS: Compared to the on-pump group, serum MDA
      levels at 30 minutes, 60 minutes, 6 hours, and 24 hours after the CABG surgery
      were significantly lower in the off-pump group (P=.001, P=.001, P=.001, and
      P=.001, respectively). Serum M30 levels were found to be elevated in both groups,
      returning to baseline at 24 hours. When compared to baseline, the hs-CRP level
      reached its peak at 24 hours at 13.28+/-5.32 mg/dL in the on-pump group, and
      15.44+/-4.02 mg/dL in the off-pump group. CONCLUSION: CABG surgery is associated
      with an increase in inflammatory markers and serum M30 levels, indicating
      epithelial/endothelial apoptosis in the early period.

PMID- 25367243
TI  - Impact of transcatheter aortic valve implantation (TAVI) on pulmonary hyper
      tension and clinical outcome in patients with severe aortic valvular stenosis.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a proven
      alternative to open heart surgery in elderly patients. Pulmonary hypertension
      (PH) is known as a significant risk factor in patients with severe aortic
      stenosis (AS) undergoing surgical aortic valve replacement. However, the
      prognostic impact of PH in high-risk patients undergoing TAVI is still unknown.
      The aim of this study was to gain more insight in the clinical outcome and
      mortality of patients with PH after TAVI. METHODS AND RESULTS: Between July 2009
      and September 2012, a total of 439 patients were treated by TAVI in conjunction
      with a complete invasive right heart study at our institution. Patients were
      divided into two groups with regard to their pulmonary arterial mean pressure
      (PAMP) before TAVI (A: PAMP < 25 mmHg and B: PAMP >= 25 mmHg). Patients with
      baseline PH had a significantly higher logES (A: 19.40 vs. B: 28.17 %; p < 0.001)
      and were more frequently in NYHA functional class IV (A: 15.4 vs. B: 25.1 %; p =
      0.013). Invasive right heart data demonstrated an immediate improvement after
      TAVI in patients with PH. Despite a similar clinical benefit among survivors, 30
      day and 1-year mortality were higher in patients with PH (30-day mortality: A:
      4.8 vs. B: 10.4 %; p = 0.021, 1 year mortality: A: 13.9 vs. B: 23.4 %; p =
      0.014). CONCLUSIONS: Pulmonary hypertension is an independent risk factor for
      survival after TAVI. Nevertheless, TAVI leads to an acute improvement of nearly
      all invasively assessed variables in patients with PH, with a similar improvement
      in functional NYHA class compared to patients without PH, indicating a similar
      benefit among survivors.

PMID- 25367244
TI  - Detection of coronary artery disease in postmenopausal women: the significance of
      integrated stress imaging tests in a 4-year prognostic study.
AB  - BACKGROUND: The present prospective study investigated whether a combined
      approach integrating two different stress imaging modalities may improve the
      diagnostic accuracy and prognostic impact of non-invasive coronary artery disease
      (CAD) tests in postmenopausal women. In women non-invasive tests for detecting
      CAD are less accurate than in men, leading to a high proportion of unnecessary
      coronary angiographies (CAs). METHODS: 424 consecutive postmenopausal women (mean
      61 +/- 7 years, mean Reynolds Risk Score 13 +/- 3 %) with symptoms suggestive of
      CAD were prospectively included and followed up for 4 +/- 1 years. Each patient
      underwent CA, stress cardiovascular magnetic resonance (CMR) by adenosine,
      dobutamine stress echocardiography (DSE) and single-photon emission computed
      tomography (SPECT) within 7 +/- 3 days. RESULTS: Anatomically obstructive
      coronary artery disease (>=50 % diameter stenosis) was present in 157 women (37
      %). The combination of two stress imaging modalities significantly increased the
      positive predictive values (PPV) to 90 +/- 3, 88 +/- 3 and 87 +/- 2 % for
      CMR/DSE, DSE/SPECT and CMR/SPECT, respectively. For patients with negative
      combined test results, the survival analysis showed a 4-year cumulative event
      free survival rate of 96-97 % for all combinations. This new approach is cost
      effective due to the resulting reduction in unnecessary CAs (with potential side
      effects and corresponding therapies) as well as reducing hospitalization time.
      CONCLUSIONS: In symptomatic postmenopausal women, combination of two negative
      stress imaging results significantly increases the PPV for detection of CAD and
      excludes future cardiovascular events with high accuracy. This approach may be
      applied to improve the prognostic precision of non-invasive CAD tests and to
      avoid unnecessary CAs.

PMID- 25367245
TI  - A more than six orders of magnitude UV-responsive organic field-effect transistor
      utilizing a benzothiophene semiconductor and Disperse Red 1 for enhanced charge
      separation.
AB  - A more than six orders of magnitude UV-responsive organic field-effect transistor
      is developed using a benzothiophene (BTBT) semiconductor and strong donor
      acceptor Disperse Red 1 as the traps to enhance charge separation. The device can
      be returned to its low drain current state by applying a short gate bias, and is
      completely reversible with excellent stability under ambient conditions. 

PMID- 25367246
TI  - Chronic effects of shift work on cognition: findings from the VISAT longitudinal
      study.
AB  - OBJECTIVES: Shift work, like chronic jet lag, is known to disrupt workers' normal
      circadian rhythms and social life, and to be associated with increased health
      problems (eg, ulcers, cardiovascular disease, metabolic syndrome, breast cancer,
      reproductive difficulties) and with acute effects on safety and productivity.
      However, very little is known about the long-term consequences of shift work on
      cognitive abilities. The aim of this study was to assess the chronicity and
      reversibility of the effects of shift work on cognition. METHODS: We conducted a
      prospective cohort study of 3232 employed and retired workers (participation
      rate: 76%) who were 32, 42, 52 and 62 years old at the time of the first
      measurement (t1, 1996), and who were seen again 5 (t2) and 10 (t3) years later.
      1484 of them had shift work experience at baseline (current or past) and 1635 had
      not. The main outcome measures were tests of speed and memory, assessed at all
      three measurement times. RESULTS: Shift work was associated with impaired
      cognition. The association was stronger for exposure durations exceeding 10 years
      (dose effect; cognitive loss equivalent to 6.5 years of age-related decline in
      the current cohort). The recovery of cognitive functioning after having left
      shift work took at least 5 years (reversibility). CONCLUSIONS: Shift work
      chronically impairs cognition, with potentially important safety consequences not
      only for the individuals concerned, but also for society.

PMID- 25367247
TI  - Ex vivo digestion of carp muscle tissue--ACE inhibitory and antioxidant
      activities of the obtained hydrolysates.
AB  - In the digestive tract of humans, bioactive peptides, i.e. protein fragments
      impacting the physiological activity of the body, may be released during the
      digestion of food proteins, including those of fish. The aim of the study was to
      establish the method of human ex vivo digestion of carp muscle tissue and
      evaluate the angiotensin I-converting enzyme inhibitory and antioxidant
      activities of hydrolysates obtained after digestion. It was found that the
      hydrolysates of carp muscle tissue obtained with the three-stage method of
      simulated ex vivo digestion showed ACE inhibitory as well as antioxidative
      activities. It was demonstrated that the degree of hydrolysis depended on the
      duration of individual stages and the degree of comminution of the examined
      material. Although the applied gastric juices initiated the process of hydrolysis
      of carp muscle tissue, the duodenal juices caused a rapid increase in the amount
      of hydrolysed polypeptide bonds. The antihypertensive and antioxidative
      activities of the hydrolysates of carp muscle tissue increased together with
      progressive protein degradation. However, the high degree of protein hydrolysis
      does not favour an increase in the activity of free radical scavenging. The
      presented results are an example of the first preliminary screening of the
      potential health-promoting biological activity of carp muscle tissue in an ex
      vivo study. 

PMID- 25367248
TI  - Technical tip and cost analysis for lesser toe plantar plate repair with a curved
      suture needle.

PMID- 25367249
TI  - Ultrasound-guided alcohol injection for Morton's neuroma.
AB  - BACKGROUND: Ultrasonography-guided alcohol injection (USGAI) of Morton's neuroma
      represents an alternative to operative treatment. Nonetheless, the literature
      only reports few small studies evaluating the effectiveness of the treatment. The
      aim of the present retrospective study was to assess the effectiveness of USGAI
      to treat Morton's neuroma in 508 patients at 2 medical centers. METHODS: Between
      January 2001 and January 2012, 508 patients with 540 Morton's neuroma had USGAI
      for Morton's neuroma. Only second and third web-space neuromas were included in
      this study. RESULTS: A mean number of 3.0 (range, 1 to 4) injections were
      performed for each neuroma. Mean local inflammatory reaction was 0.7 (range, 0 to
      2). There were no other local or systemic complications. The overall mean pre
      USGAI VAS score was 8.7 (range, 6 to 10), while the post-USGAI VAS score at 1
      year was 3.6 (range, 0 to 9). The delta VAS between the pre- and post-USGAI was
      statistically significant (P < .0001). At 1-year follow-up 74.5% of patients were
      satisfied with the procedure. CONCLUSION: USGAI produced encouraging results in
      over 500 patients affected by Morton's neuroma. The procedure proved to be safe
      in all patients. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 25367250
TI  - Initial hospital-related cost comparison of total ankle replacement and ankle
      fusion with hip and knee joint replacement.
AB  - BACKGROUND: Total hip and knee arthroplasty (THA and TKA) are accessible to
      patients with end-stage hip and knee arthritis in most health care systems. The
      availability of total ankle arthroplasty (TAA) to patients with end-stage ankle
      arthritis is often restricted because of prosthesis cost. Ankle fusion (AF) is
      often offered as the only alternative. Patients should have equal access to
      procedures that are equivalent in total cost. We compared total costs of TAA, AF,
      THA, and TKA for similar cohorts in a government-funded teaching hospital.
      METHODS: A subset of 13 TAA and 13 AF patients were selected from the Canadian
      Orthopaedic Foot and Ankle Society Prospective Ankle Reconstruction Database, and
      13 THA and 13 TKA patients were randomly selected from the Canadian Joint
      Replacement Registry. Total cost was estimated from operating room time, hospital
      stay, surgeon billing, and equipment used. RESULTS: Mean total cost associated
      with TAA was $13,500 +/- 1000 and was the same as THA ($14,500 +/- 1500) and TKA
      ($12,500 +/- 1000). Mean total cost associated with AF was significantly less at
      $5500 +/- 500. Mean operating room time was longer, but mean hospital stay was
      shorter for the ankle procedures compared with THA and TKA. CONCLUSION: All
      arthroplasties had similar total costs. Total ankle arthroplasty should not be
      denied based on prosthetic cost alone, as total procedure cost is equivalent to
      THA and TKA. We believe ankle fusion is a less expensive and preferable
      alternative for some patient groups.

PMID- 25367251
TI  - Analysis of PITFL injuries in rotationally unstable ankle fractures.
AB  - BACKGROUND: Reduction and stabilization of the syndesmosis in unstable ankle
      fractures is important for ankle mortise congruity and restoration of normal
      tibiotalar contact forces. Of the syndesmotic ligaments, the posterior inferior
      tibiofibular ligament (PITFL) provides the most strength for maintaining
      syndesmotic stability, and previous work has demonstrated the significance of
      restoring PITFL function when it remains attached to a posterior malleolus
      fracture fragment. However, little is known regarding the nature of a PITFL
      injury in the absence of a posterior malleolus fracture. The goal of this study
      was to describe the PITFL injury pattern based on magnetic resonance imaging
      (MRI) and intraoperative observation. METHODS: A prospective database of all
      operatively treated ankle fractures by a single surgeon was used to identify all
      supination-external rotation (SER) types III and IV ankle fracture patients with
      complete preoperative orthogonal ankle radiographs and MRI. All patients with a
      posterior malleolus fracture were excluded. Using a combination of preoperative
      imaging and intraoperative findings, we analyzed the nature of injuries to the
      PITFL. In total, 185 SER III and IV operatively treated ankle fractures with
      complete imaging were initially identified. RESULTS: Analysis of the preoperative
      imaging and operative reports revealed 34% (63/185) had a posterior malleolus
      fracture and were excluded. From the remaining 122 ankle fractures, the PITFL was
      delaminated from the posterior malleolus in 97% (119/122) of cases. A smaller
      proportion (3%; 3/122) had an intrasubstance PITFL rupture. CONCLUSIONS: Accurate
      and stable syndesmotic reduction is a significant component of restoring the
      ankle mortise after unstable ankle fractures. In our large cohort of rotationally
      unstable ankle fractures without posterior malleolus fractures, we found that
      most PITFL injuries occur as a delamination off the posterior malleolus. This
      predictable PITFL injury pattern may be used to guide new methods for stabilizing
      the syndesmosis in these patients. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 25367252
TI  - Reconstruction of the medial talonavicular joint in simulated flatfoot deformity.
AB  - BACKGROUND: Reconstructing the ligamentous constraints of the medial arch
      associated with adult acquired flatfoot deformity remains a challenge. The
      purpose of this study was to test the efficacy of several reconstruction
      techniques of the medial arch. We hypothesized that an anatomic reconstruction of
      the spring ligament complex would correct the deformity better than other
      techniques tested. METHODS: Three reconstructions of the medial support
      structures were performed on each specimen to recreate the different lines of
      action and insertions of the medial ligamentous complex in 12 specimens with a
      simulated flatfoot deformity. Talonavicular and tibiocalcaneal (hindfoot)
      orientations were measured in the axial, sagittal, and coronal planes in the
      intact, flatfoot, and reconstructed conditions. RESULTS: While each
      reconstruction technique corrected the deformity (P < .05), proximal fixation of
      the graft corrected the greatest amount of talonavicular deformity while also
      correcting hindfoot valgus (P < .05). CONCLUSION: The fixation points and lines
      of action of a medial arch reconstruction have important implications on
      deformity correction in a flatfoot model. Despite its fidelity to the native
      structure, the anatomic spring ligament reconstruction provided the least amount
      of correction. These findings suggest that other ligamentous structures of the
      medial arch are critical in supporting the midfoot. CLINICAL RELEVANCE:
      Reconstruction of the ligamentous supports of the medial arch might be able to
      correct substantial amounts of deformity without osseous procedures like
      calcaneal osteotomies or midfoot fusions.

PMID- 25367253
TI  - Predictors of response to physical therapy intervention for plantar heel pain.
AB  - BACKGROUND: Age, weight, and duration of symptoms have been associated with a
      poor response to treatment for plantar heel pain (PHP), but no studies were
      identified that examined predictors of response to physical therapy intervention.
      The purpose of this investigation was to examine the influence of age, body mass
      index (BMI), and symptom duration on treatment response to physical therapy
      intervention. METHODS: Sixty participants received 6 visits over 4 weeks of
      physical therapy intervention that included manual therapy and exercise or
      electrophysiological agents and exercise. Outcomes were assessed using the Foot
      and Ankle Ability Measure (FAAM), Numeric Pain Rating Scale (NPRS), and Global
      Rating of Change Scale (GRC). Logistic regression (P < .05) was used to analyze
      age, BMI, and symptom duration as potential predictors of a successful response
      based on the minimal clinically important difference of the outcome measures.
      Sensitivity analysis was used to assess the influence of success based on minimal
      clinically important changes in the FAAM, NPRS, and GRC or only the FAAM and
      NPRS. Receiver operating curves were used to determine the cut point for the
      significant predictor. RESULTS: At the 6-month follow-up to physical therapy
      intervention, NPRS was improved by 3 points (95% CI, 2.4-3.6) and FAAM improved
      by 22.5 points (95% CI, 16.8-28.2). Individuals with symptoms less than 7.2
      months were 4.2 (95% CI, 1.3-13.8; P = .016) and 8.5 (95% CI, 2.5-28.9; P = .001)
      times more likely to respond to treatment based on the NPRS/FAAM/GRC and
      NPRS/FAAM success criteria, respectively. Age and BMI were not significant
      predictors (P >= .455 and P >= .450, respectively). CONCLUSION: Age and BMI were
      not associated with outcomes and obese individuals did achieve a successful
      outcome with the physical therapy intervention used in the clinical trial.
      Individuals with PHP symptoms longer than 7 months require additional
      consideration and further investigation of effective strategies to improve
      treatment response. LEVEL OF EVIDENCE: Prognosis, level 2b comparative study.

PMID- 25367254
TI  - Role of miRNA in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy
      worldwide. Evidence suggests that miRNAs play an important role in progression,
      recurrence, metastasis and postoperative survival of HNSCC. Studies have
      investigated the utility of miRNAs as diagnostic/prognostic tools and as
      potential therapeutic targets and biomarkers that may improve the management and
      outcomes of HNSCC. The aim of this article is to review the current literature on
      aberrant expression profiles of miRNAs in biopsy samples of HNSCC and their role
      in cancer development, metastasis, prognosis and survival of these patients. This
      review gives an overview that miRNAs deregulation play major role in the
      development of HNSCC. They offer the potential to be used as biomarkers or novel
      therapeutic targets. Future research is required to test their use in both of
      these fields. 

PMID- 25367256
TI  - Surveillance for Toxoplasma gondii in California mussels (Mytilus californianus)
      reveals transmission of atypical genotypes from land to sea.
AB  - Coastal habitat contamination with Toxoplasma gondii is a health risk to humans
      and marine wildlife, with infections documented in both nearshore and pelagic
      marine mammals. Due to lack of sensitive methods for detection of T. gondii in
      water, this study utilized an alternative surveillance approach for evaluating
      marine habitat contamination using wild mussels. The objectives of this study
      were to (i) validate sensitive molecular tools for T. gondii detection in mussels
      and (ii) apply optimized methods in a surveillance study to determine the
      prevalence and genotype(s) of T. gondii in mussels. Simplex polymerase chain
      reaction screening and multiplex genotyping assays were validated and then
      applied on 959 wild-caught mussels collected from central California. Thirteen
      mussels (1.4%) had detectable T. gondii DNA and the presence of T. gondii in
      mussels was significantly associated with proximity to freshwater run-off and
      collection during the wet season. Molecular characterization revealed alleles
      from T. gondii types I, II/III, X at the B1 locus, and a novel atypical B1 allele
      that was recently documented in T. gondii-infected carnivores from California.
      Findings demonstrate higher than previously reported T. gondii contamination of
      California coastlines, and describe novel strains of the parasite that further
      link terrestrial sources with marine contamination. 

PMID- 25367255
TI  - AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p
      Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse
      tissues.
AB  - BACKGROUND: The Aurora family of serine-threonine kinases are essential
      regulators of cell division in mammalian cells. Aurora-A and -B expression and
      kinase activity is elevated in a variety of human cancers and is associated with
      high proliferation rates and poor prognosis. AMG 900 is a highly potent and
      selective pan-aurora kinase inhibitor that has entered clinical evaluation in
      adult patients with advanced cancers. In mice, oral administration of AMG 900
      blocks the phosphorylation of histone H3 on serine-10 (p-Histone H3), a proximal
      substrate of aurora-B and inhibits the growth of multiple human tumor xenografts,
      including multidrug-resistant models. METHODS: In order to establish a
      preclinical pharmacokinetic-pharmacodynamic (PK-PD) relationship for AMG 900 that
      could be translated to the clinic, we used flow cytometry and laser scanning
      cytometry detection platforms to assess the effects on p-Histone H3 inhibition in
      terms of sensitivity, precision, and specificity, in human tumor xenografts in
      conjunction with mouse skin and bone marrow tissues. Mice with established COLO
      205 tumors were administered AMG 900 at 3.75, 7.5, and 15 mg/kg and assessed
      after 3 hours. RESULTS: Significant suppression of p-Histone H3 in mouse skin was
      only observed at 15 mg/kg (p <0.0001), whereas in mouse bone marrow and in tumor
      a dose-dependent inhibition was achieved at all three doses (p <= 0.00015). These
      studies demonstrate that AMG 900 inhibits p-Histone H3 in tumors and surrogate
      tissues (although tissues such as skin may be less sensitive for assessing PD
      effects). To further extend our work, we evaluated the feasibility of measuring p
      Histone H3 using fine-needle aspirate (FNA) tumor xenograft biopsies. Treatment
      with AMG 900 significantly inhibited p-Histone H3 (>99% inhibition, p <0.0001) in
      COLO 205 tumors. Lastly, we illustrate this LSC-based approach can detect p
      Histone H3 positive cells using mock FNAs from primary human breast tumor
      tissues. CONCLUSION: Phosphorylation of histone H3 is a useful biomarker to
      determine the pharmacodynamics (PD) activity of AMG 900. FNA biopsies may be a
      viable approach for assessing AMG 900 PD effects in the clinic.

PMID- 25367257
TI  - Photocatalytic reduction of hexavalent chromium with illuminated amorphous FeOOH.
AB  - In this study, photocatalytic reduction of hexavalent chromium [Cr(VI)] by
      amorphous FeOOH was investigated with variations in FeOOH dosage, pH, initial
      Cr(VI) concentration, purging gas, organic compounds and initial hydrogen
      peroxide concentration. Reduction and adsorption were identified as important
      processes for the removal of Cr(VI). FeOOH dosage was also an important parameter
      for the removal of Cr(VI). As the FeOOH dosage increased up to 0.5 g/L, the
      removal of Cr(VI) was continuously enhanced and then decreased above 0.5 g/L due
      to increased blockage of the incident UV light. The removal efficiency of Cr(VI)
      decreased with increasing pH, initial Cr(VI) concentration and initial hydrogen
      peroxide concentration. While the removal efficiency of Cr(VI) increased with
      purging of nitrogen gas compared to that of oxygen gas because of less
      competition between dissolved oxygen and Cr(VI) with the electron in the
      conduction band of FeOOH. The photocatalytic reduction of Cr(VI) was increased in
      the presence of citric acid and phenol, while it was decreased in the presence of
      EDTA and oxalic acid. The reaction rate constant (kobs) was decreased from 0.2141
      to 0.0026 1/min and the value of electrical energy per order (EEo) was increased
      from 22.41 to 1846.15 (kWh/m3) with increasing initial Cr(VI) concentration from
      10 to 50 mg/L, respectively. Finally, proper photocatalytic activity was
      maintained even after five successive cycles.

PMID- 25367258
TI  - Short- and long-term outcomes of laryngeal cancer care in the elderly.
AB  - OBJECTIVES/HYPOTHESIS: To examine associations between pretreatment variables,
      short-term and long-term swallowing and airway impairment, and survival in
      elderly patients treated for laryngeal squamous cell cancer (SCCA). STUDY DESIGN:
      Retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare
      data. METHODS: Longitudinal data from 2,370 patients diagnosed with laryngeal
      SCCA from 2004 to 2007 were evaluated using cross-tabulations, multivariate
      logistic regression, and survival analysis. RESULTS: Dysphagia (odds ratio [OR] =
      1.5 [1.2-1.7]), weight loss (OR = 1.3 [1.1-1.6]), esophageal stricture (OR = 3.8
      [2.5-5.9]), airway obstruction (OR = 1.9, [1.6-2.3]), tracheostomy (OR = 1.5 [1.2
      1.9]), and pneumonia (OR = 1.8 [1.4-2.2]) increased 1 year after treatment. The
      odds of airway obstruction, esophageal stricture, and pneumonia increased over
      subsequent years, with significantly increased risk at 5 years for airway
      obstruction (OR = 3.3 [1.8-5.8]) and pneumonia (OR = 5.2 [2.5-10.7]).
      Pretreatment dysphagia, chemoradiation, and salvage surgery were significant
      predictors of long-term dysphagia, weight loss, tracheostomy, and gastrostomy,
      with pretreatment dysphagia and salvage surgery also associated with pneumonia.
      Surgery and postoperative radiation was associated with long-term dysphagia (OR =
      1.4 [1.0-1.9]) but reduced odds of long-term pneumonia (OR = 0.7 [0.5-0.9]). Long
      term dysphagia, gastrostomy or tracheostomy dependence, weight loss, airway
      obstruction, and pneumonia were associated with poorer survival, with pneumonia
      associated with the greatest risk of death at 5 years (hazard ratio = 2.6 [2.4
      2.9]). CONCLUSIONS: Airway and swallowing impairment is common after laryngeal
      SCCA treatment in elderly patients, increases over time, and is associated with
      poorer survival-with pneumonia associated with the highest risk of long-term
      mortality. Patients with pretreatment dysphagia, initial treatment with
      chemoradiation, and salvage surgery represent a high-risk group with an increased
      risk of disability and death.

PMID- 25367259
TI  - Diabetes connect: African American men's preferences for a community-based
      diabetes management program.
AB  - PURPOSE: The purpose of the study is to explore African American men's
      perceptions of how community-based, community-health worker (CHW)-delivered
      diabetes interventions might best be implemented. METHODS: Four 90-minute focus
      groups were guided by a trained moderator with a written guide to facilitate
      discussion on the topic of diabetes management and preferences for community
      based programs. Participants were recruited from the diabetes education database
      at a safety-net health system in Jefferson County, AL. Two independent reviewers
      performed content analysis to identify major themes using an iterative, combined
      deductive and inductive approach. RESULTS: There were 25 male participants. Mean
      years living with diabetes was 9.6 (range, 1-20). Participants demonstrated
      knowledge of self-management strategies and identified various hardships
      including emotional and physical manifestations of diabetes, dietary
      restrictions, and institutional frustrations with the health system that
      contributed to self-management barriers. Their preferred CHW responsibilities
      were to educate, hold support groups, help track daily activities, and help find
      resources. Potential concerns included the need for confidentiality and fears of
      being stereotyped. CONCLUSIONS: Participants identified critical self-management
      strategies but endure hardships that present barriers to daily diabetes
      management. Preferences for community-based programs and suggested CHW
      responsibilities could help to overcome many of those barriers by increasing
      access and providing support.

PMID- 25367260
TI  - Metabolic and biochemical changes in plasma of the periparturient rabbit does
      with different litter size.
AB  - The aim of this study was to investigate the metabolic and biochemical changes in
      plasma that occur in the reproductive rabbit doe close to the parturition, as
      well as if the number of offspring affects the metabolism and the health status
      of the doe. At -3, 4 and 12 days from parturition (-D3, D4, and D12,
      respectively) nine rabbit does at their third parity from a commercial hybrid
      line (HYPLUS PS 19) selected for high prolificacy were weighted and blood was
      collected for a wide inflammometabolic profile. According to the number of
      offspring the does were retrospectively divided in two groups: high litter size
      group (HI; n=5) and low litter size group (LO; n=4). BW was higher (P<0.01) at 
      D3 and had the lowest values at D4. At D12, the BW was lower (P<0.05) in LO
      compared with HI. Several metabolites significantly changed from dry to lactation
      period. Glucose and cholesterol had the lowest levels at -D3; non-esterified
      fatty acid (NEFA) and aspartate aminotransferase had the highest values before
      parturition (P<0.05); creatinine and beta-hydroxybutyrate (BHBA) were higher at 
      D3 with respect to D4 (P<0.05). The lowest value of paraoxonase was observed in
      does at -D3 (P<0.05), whereas at this time ceruloplasmin and total bilirubin had
      the highest concentration (P<0.05). The differences for blood profile parameters
      between does grouped according to litter size were mainly evident before
      parturition (-D3). In particular, BHBA, NEFA and total bilirubin had higher
      concentrations (P<0.05) in HI v. LO group, whereas albumin and PON were lower in
      HI group (P<0.01). After parturition there were no significant differences for
      the metabolic parameters between the two groups. The results show that for
      reproductive rabbit doe the last days of gestation are very stressful from a
      metabolic and inflammatory point of view. The genetic selection of does for
      higher litter size has increased their ability to mobilize body reserves in order
      to guarantee the nutrients to a high number of kits. This exposes them to a more
      severe metabolic and inflammatory challenge during the transition period.
      Consequently, feeding and managerial strategies for high prolificacy
      periparturient rabbit does should be revised. 

PMID- 25367261
TI  - Serofendic acid protects against myocardial ischemia-reperfusion injury in rats.
AB  - We previously reported that serofendic acid, a lipophilic extract of fetal calf
      serum, protects against oxidative stress in primary culture of neonatal rat
      cardiomyocytes. However, the effect of serofendic acid on myocardial ischemia
      reperfusion injury in vivo is yet to be determined. In the present study, we
      investigated the effect of intravenous administration of serofendic acid on
      ischemia-reperfusion injury induced by transient occlusion of the left coronary
      artery in rats. The rat heart was subjected to 25-min ischemia followed by 2-h
      reperfusion. Bolus intravenous administration of serofendic acid (1-10 mg/kg)
      given twice reduced the infarct volume in a dose-dependent manner. The protective
      effect of serofendic acid was abolished by pretreatment with 5-hydroxydecanoate,
      a blocker of mitochondrial ATP-sensitive potassium channels. For further testing
      of the protective effect of serofendic acid at the subcellular level, we
      monitored mitochondrial membrane potential (MMP) in individual cells using real
      time two-photon imaging of Langendorff-perfused rat heart. A 25-min no-flow
      ischemia, followed by reperfusion caused progressive MMP loss. Serofendic acid
      significantly reduced the number of cells undergoing MMP loss. These results
      suggest that serofendic acid protected cardiac myocytes against myocardial
      ischemia-reperfusion injury by preserving the functional integrity of
      mitochondria.

PMID- 25367262
TI  - New experimental trends for phosphoinositides research on ion transporter/channel
      regulation.
AB  - Phosphoinositides(4,5)-bisphosphates [PI(4,5)P2] critically controls membrane
      excitability, the disruption of which leads to pathophysiological states.
      PI(4,5)P2 plays a primary role in regulating the conduction and gating properties
      of ion channels/transporters, through electrostatic and hydrophobic interactions
      that allow direct associations. In recent years, the development of many
      molecular tools have brought deep insights into the mechanisms underlying
      PI(4,5)P2-mediated regulation. This review summarizes the methods currently
      available to manipulate the cell membrane PI(4,5)P2 level including
      pharmacological interventions as well as newly designed molecular tools. We
      concisely introduce materials and experimental designs suitable for the study of
      PI(4,5)P2-mediated regulation of ion-conducting molecules, in order to assist
      researchers who are interested in this area. It is our further hope that the
      knowledge introduced in this review will help to promote our understanding about
      the pathology of diseases such as cardiac arrhythmias, bipolar disorders, and
      Alzheimer's disease which are somehow associated with a disruption of PI(4,5)P2
      metabolism. 

PMID- 25367263
TI  - Capacity, responsibility, and motivation: a critical qualitative evaluation of
      patient and practitioner views about barriers to self-management in people with
      multimorbidity.
AB  - BACKGROUND: Primary care is increasingly focussed on the care of people with two
      or more long-term conditions (multimorbidity). The UK Department of Health
      strategy for long term conditions is to use self-management support for the
      majority of patients but there is evidence of limited engagement among primary
      care professionals and patients with multimorbidity. Furthermore, multimorbidity
      is more common in areas of socioeconomic deprivation but deprivation may act as a
      barrier to patient engagement in self-management practices. BACKGROUND: Effective
      self-management is considered critical to meet the needs of people living with
      long term conditions but achieving this is a significant challenge in patients
      with multimorbidity. This study aimed to explore patient and practitioner views
      on factors influencing engagement in self-management in the context of
      multimorbidity. METHODS: A qualitative study using individual semi-structured
      interviews with 20 patients and 20 practitioners drawn from four general
      practices in Greater Manchester situated in areas of high and low social
      deprivation. RESULTS: Three main factors were identified as influencing patient
      engagement in self-management: capacity (access and availability of socio
      economic resources and time; knowledge; and emotional and physical energy),
      responsibility (the degree to which patients and practitioners agreed about the
      division of labour about chronic disease management, including self-management)
      and motivation (willingness to take-up types of self-management practices).
      Socioeconomic deprivation negatively impacted on all three factors. Motivation
      was especially reduced in the presence of mental and physical multimorbidity.
      CONCLUSION: Full engagement in self-management practices in multimorbidity was
      only present where patients' articulated a sense of capacity, responsibility, and
      motivation. Patient 'know-how' or interpretive capacity to self-manage
      multimorbidity is potentially an important precursor to responsibility and
      motivation, and might be a critical target for intervention. However, individual
      and social resources are needed to generate capacity, responsibility, and
      motivation for self-management, pointing to a balanced role for health services
      and wider enabling networks.

PMID- 25367264
TI  - Temporary anion states of p-benzoquinone: shape and core-excited resonances.
AB  - The studies of shape and core-excited resonances are essential in the bonding and
      electronic processes of quinones. So far, the experimental results of temporary
      anion states for p-benzoquinone cannot be fully ascertained computationally. In
      this paper, both resonances of p-benzoquinone are investigated via the
      stabilization method (SM). For shape resonances, the stabilized Koopmans theorem
      is adopted in the framework of long range corrected density functional theory (LC
      DFT). As for core-excited resonances, the SM coupled with long range corrected
      time-dependent density functional theory (LC-TDDFT) is employed. The resonance
      energies and lifetimes are then estimated via an analytic continuation procedure
      in conjunction with the stabilization plots. Using this novel combination,
      previous experimental results of temporary anion states can be successfully
      identified. It is believed that this novel approach can be an accurate and
      efficient methodology in the study of temporary anion states of quinones. 

PMID- 25367265
TI  - Academic and social integration on campus among sexual minority students: the
      impacts of psychological and experiential campus climate.
AB  - A heterosexist campus climate can increase risk for mental health problems for
      sexual minority students; however, the relationship between campus climate for
      sexual minorities and academic outcomes remains understudied. Using a sample of
      sexual minority respondents extracted from a campus climate survey conducted at a
      large university in the Midwest, we examine relationships between multiple
      dimensions of psychological and experiential campus climate for sexual minorities
      with academic integration (academic disengagement, grade-point average [GPA]) and
      social integration (institutional satisfaction, acceptance on campus). We also
      investigate the protective role of engagement with informal academic and peer
      group systems. Findings suggest campus climate affects sexual minority students'
      integration. In multivariate analyses, perceptions of whether lesbian, gay, and
      bisexual (LGB) people could be open about their sexual identity was positively
      associated with acceptance on campus; personal heterosexist harassment was
      positively associated with academic disengagement and negatively with GPA.
      Students' informal academic integration (instructor relations) and informal
      social integration (LGB friends) demonstrated influential main effects but did
      not moderate any of the climate-outcome relationships. Researchers should further
      explore the relationships between climate and academic outcomes among sexual
      minority students, both collectively and among specific sub-groups, and address
      the role of other protective factors. 

PMID- 25367266
TI  - Learning in third spaces: community art studio as storefront university
      classroom.
AB  - Third spaces are in-between places where teacher-student scripts intersect,
      creating the potential for authentic interaction and a shift in what counts as
      knowledge. This paper describes a unique community-university initiative: a third
      space storefront classroom for postsecondary students in professional education
      programs, which also functions as a community art studio for the surrounding
      neighborhood. This approach to professional education requires an innovative
      combination of theory, methods, and materials as enacted by the professionals
      involved and performed by the students. This storefront classroom utilizes
      collaborative and inclusive instructional practices that promote human and
      community development. It facilitates the use of innovative instructional
      strategies including art making and participatory dialogue to create a liminal
      learning space that reconfigures professional education. In researching the
      effectiveness of this storefront classroom, we share the voices of students who
      have participated in this third space as part of their coursework to underscore
      these principles and practices. 

PMID- 25367267
TI  - Women creating public art and community, 2000-2014.
AB  - This narrative describes a series of 15 short-term public art projects that were
      part of a program for women and girls in Lowell, Massachusetts, a mid-size city
      in the United States. The projects were designed to give public space to women's
      stories and perspectives by exhibiting their creative art in response to
      suggested themes. A few thousand women and girls representing diverse age and
      cultural groups created art based on their lived experiences. The organizers of
      the program met people in comfortable settings, tailored their art-making
      approaches to particular groups, and used inclusive processes in developing and
      executing the program. Program successes and challenges were related to the
      organizational structure of the art projects, the annual themes and art media,
      the extent of outreach and support, the process of creation, and the impact of
      art exhibits. Using community psychology and feminist frameworks, authors reflect
      on the projects and their relevance across contexts, highlight key organizing
      strategies, and identify ways the project represents community psychology in
      action. 

PMID- 25367268
TI  - Tumour suppressor gene methylation and cervical cell folate concentration are
      determinants of high-risk human papillomavirus persistence: a nested case control
      study.
AB  - BACKGROUND: Persistent infection with one or more high-risk human papillomavirus
      [HR-HPV] types increases the risk of intraepithelial neoplasia and cervical
      cancer. A nested case-control study was conducted to investigate the importance
      of cervical cell folate concentration and tumour suppressor gene methylation as
      risk factors for HR-HPV persistence. METHODS: Cervical cell samples from 955
      women with HR-HPV infection and normal, borderline or mild dyskaryosis were
      retrieved from the archive of a population-based screening trial. Women were
      classified as cases or controls, reflecting the presence or absence
      [respectively] of any HR-HPV infection at a follow-up clinic at least 6 months
      from baseline. Cervical cell folate concentration and promoter methylation of
      five tumour suppressor genes were measured in independent samples from cases and
      controls. RESULTS: A higher cervical cell folate concentration [P = 0.015] was an
      independent predictor of infection at follow-up, together with infection with HPV
      16 or infection with multiple HR-HPV types. Methylation of the tumour suppressor
      gene DAPK was associated with a 2.64-fold [95% CI, 1.35-5.17] increased
      likelihood of HPV infection whilst CDH1 methylation was associated with a 0.53
      fold [95% CI, 0.331-0.844] likelihood of HR-HPV infection at follow-up. When
      considering women with normal or abnormal cytology, the predictive effect of
      higher cervical cell folate was only seen in women with mild cytology [P =
      0.021]; similarly the effect of DAPK methylation was seen in women with mild or
      borderline cytology [P < 0.05]. CONCLUSIONS: Higher cervical cell folate
      concentration and promoter methylation of the tumour suppressor gene, DAPK, in
      women with cervical cell dyskaryosis, are associated with increased risk of HR
      HPV persistence.

PMID- 25367269
TI  - Effect of HIV status on fertility desire and knowledge of long-acting reversible
      contraception of postpartum Malawian women.
AB  - The objectives of this study were to describe the most recent pregnancy
      intentions and family planning preferences of HIV-infected and HIV-uninfected
      postpartum Malawian women, and to assess whether HIV status is associated with
      fertility desire and knowledge of intrauterine contraception (IUC) and the
      subdermal contraceptive implant. We conducted a cross-sectional analysis of the
      baseline characteristics of Malawian women enrolled in a prospective cohort study
      assessing postpartum contraceptive uptake and continuation. Women at a government
      hospital completed a baseline survey assessing reproductive history, family
      planning preferences, and knowledge of IUC and the implant. We used Pearson's chi
      square tests to compare these parameters between HIV-infected and HIV-uninfected
      women. Modified Poisson regression was performed to assess the association
      between HIV status and fertility desire and knowledge about IUC and the implant.
      Of 634 postpartum women surveyed, HIV-infected women were more likely to report
      their most recent pregnancy was unintended (49% vs. 37%, p = 0.004). Nearly all
      women (97%) did not want a child in the next 2 years, but HIV-infected women were
      more likely to desire no more children (adjusted prevalence ratio [PR]: 1.59; 95%
      confidence interval [CI]: 1.33, 1.89). HIV-infected women were also less likely
      to know that IUC (adjusted PR: 0.72; 95% CI: 0.61, 0.84) and the implant
      (adjusted PR: 0.83; 95% CI: 0.75, 0.92) are safe during breast-feeding.
      Postpartum women strongly desire family spacing and many HIV-infected postpartum
      women desire no more children, suggesting an important role for these long-acting
      methods. Education about the efficacy and safety of IUC and the implant
      particularly during breast-feeding may facilitate postpartum use. 

PMID- 25367270
TI  - Quantitative Analysis of HSV Gene Expression during Lytic Infection.
AB  - Herpes Simplex Virus (HSV) is a human pathogen that establishes latency and
      undergoes periodic reactivation, resulting in chronic recurrent lytic infection.
      HSV lytic infection is characterized by an organized cascade of three gene
      classes; however, successful transcription and expression of the first, the
      immediate early class, is critical to the overall success of viral infection.
      This initial event of lytic infection is also highly dependent on host cell
      factors. This unit uses RNA interference and small molecule inhibitors to examine
      the role of host and viral proteins in HSV lytic infection. Methods detailing
      isolation of viral and host RNA and genomic DNA followed by quantitative real
      time PCR allow characterization of impacts on viral transcription and
      replication, respectively. Western blots can be used to confirm quantitative PCR
      results. This combination of protocols represents a starting point for
      researchers interested in virus-host interactions during HSV lytic infection.

PMID- 25367271
TI  - Analysis of HSV Viral Reactivation in Explants of Sensory Neurons.
AB  - As with all Herpesviruses, Herpes simplex virus (HSV) has both a lytic
      replication phase and a latency-reactivation cycle. During lytic replication,
      there is an ordered cascade of viral gene expression that leads to the synthesis
      of infectious viral progeny. In contrast, latency is characterized by the lack of
      significant lytic gene expression and the absence of infectious virus.
      Reactivation from latency is characterized by the re-entry of the virus into the
      lytic replication cycle and the production of recurrent disease. This unit
      describes the establishment of the mouse sensory neuron model of HSV-1 latency
      reactivation as a useful in vivo system for the analysis of mechanisms involved
      in latency and reactivation. Assays including the determination of viral yields,
      immunohistochemical/immunofluorescent detection of viral antigens, and mRNA
      quantitation are used in experiments designed to investigate the network of
      cellular and viral proteins regulating HSV-1 lytic infection, latency, and
      reactivation.

PMID- 25367272
TI  - Vibrio cholerae: Measuring Natural Transformation Frequency.
AB  - Many bacteria can become naturally competent to take up extracellular DNA across
      their outer and inner membranes by a dedicated competence apparatus. Whereas some
      studies show that the DNA delivered to the cytoplasm may be used for genome
      repair or for nutrition, it can also be recombined onto the chromosome by
      homologous recombination: a process called natural transformation. Along with
      conjugation and transduction, natural transformation represents a mechanism for
      horizontal transfer of genetic material, e.g., antibiotic resistance genes, which
      can confer new beneficial characteristics onto the recipient bacteria. Described
      here are protocols for quantifying the frequency of transformation for the human
      pathogen Vibrio cholerae, one of several Vibrio species recently shown to be
      capable of natural transformation.

PMID- 25367273
TI  - Laboratory Maintenance of Acinetobacter baumannii.
AB  - Acinetobacter baumannii has recently drawn great interest in the microbiology
      research community due to the increase in clinical antibiotic resistance of this
      organism, and persistence of this bacterial species in the hospital environment.
      This unit outlines protocols for the growth and maintenance of A. baumannii in
      the laboratory.

PMID- 25367274
TI  - Genetic Manipulation of Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a Gram-negative nosocomial pathogen of clinical
      importance. A lack of genetic tools has hindered the research of this organism in
      the past; however, recently, various methods have been designed, modified, and
      optimized to facilitate the genetic manipulation of A. baumannii. This unit
      describes some of the recent genetic advances and new recombinant tools developed
      for this pathogen, including standard transformation and conjugation techniques
      specifically developed for the bacteria. As the need to understand the basic
      biology of A. baumannii increases with the prospect of developing new
      therapeutics, the use of the basic genetic methods herein can provide the
      critical first step to identify genes required for infection.

PMID- 25367275
TI  - The luteinising hormone surge-generating system is functional in male goats as in
      females: involvement of kisspeptin neurones in the medial preoptic area.
AB  - A luteinising hormone (LH) surge is fundamental to the induction of ovulation in
      mammalian females. The administration of a preovulatory level of oestrogen evokes
      an LH surge in ovariectomised females, whereas the response to oestrogen in
      castrated males differs among species; namely, the LH surge-generating system is
      sexually differentiated in some species (e.g. rodents and sheep) but not in
      others (e.g. primates). In the present study, we aimed to determine whether there
      is a functional LH surge-generating system in male goats, and whether
      hypothalamic kisspeptin neurones in male goats are involved in the regulation of
      surge-like LH secretion. By i.v. infusion of oestradiol (E2; 6 MUg/h) for 16 h, a
      surge-like LH increase occurred in both castrated male and ovariectomised female
      goats, although the mean peak LH concentration was lower and the mean peak of the
      LH surge was later in males compared to females. Dual staining with KISS1 in situ
      hybridisation and c-Fos immunohistochemistry revealed that E2 treatment
      significantly increased c-Fos expression in the medial preoptic area (mPOA) KISS1
      cells in castrated males, as well as ovariectomised females. By contrast, dual
      labelled cells were scarcely detected in the arcuate nucleus (ARC) after E2
      treatment in both sexes. These data suggest that kisspeptin neurones in the mPOA,
      but not those in the ARC, are involved in the induction of surge-like LH
      secretion in both male and female goats. In summary, our data show that the
      mechanism that initiates the LH surge in response to oestrogen, the mPOA
      kisspeptin neurones, is functional in male goats. Thus, sexual differentiation of
      the LH surge-generating system would not be applicable to goats.

PMID- 25367276
TI  - Low-density lipoprotein apheresis ameliorates monthly estimated glomerular
      filtration rate declines in patients with renal cholesterol crystal embolism.
AB  - The incidence of cholesterol crystal embolism (CCE) has increased along with
      increases in the prevalence of atheromatous diseases and intravascular
      procedures. CCE frequently results in the deterioration of renal function, which
      sometimes leads to end-stage renal failure. Although there has been no
      established therapy for CCE, the possibility that low-density lipoprotein
      apheresis (LDL-A) is an effective therapy for renal CCE was previously reported.
      However, whether LDL-A improves renal CCE remains uncertain. This study aimed to
      evaluate the effectiveness of LDL-A in renal CCE patients. Twelve renal CCE
      patients (9 men and 3 women, mean age 70.6 +/- 1.7 years) were included in this
      retrospective study. All patients had received LDL-A therapy, and estimated
      glomerular filtration rate (eGFR) values were examined before and after LDL-A. In
      addition, monthly changes in eGFR before and after LDL-A were calculated for each
      patient. At initial diagnosis of renal CCE, the eGFR was 35.2 +/- 4.8 mL/min/1.73
      m(2). At the initiation of LDL-A, the eGFR significantly decreased to 11.0 +/-
      1.2 mL/min/1.73 m(2), and monthly changes in eGFR reached -7.2 +/- 2.5
      mL/min/1.73 m(2)/month. After the initiation of LDL-A, the progression of renal
      dysfunction stabilized in nearly two-thirds of patients, and monthly changes in
      eGFR after LDL-A significantly diminished to -0.3 +/- 0.7 mL/min/1.73 m(2)/month
      (p < 0.05 vs. before LDL-A). Although 4 patients had to undergo hemodialysis, all
      patients were alive over 1 year after the initiation of LDL-A. LDL-A therapy
      ameliorated renal dysfunction in renal CCE patients.

PMID- 25367277
TI  - Esophageal acid stimulation alters insular cortex functional connectivity in
      gastroesophageal reflux disease.
AB  - BACKGROUND: The insula plays a significant role in the interoceptive processing
      of visceral stimuli. We have previously shown that gastroesophageal reflux
      disease (GERD) patients have increased insular cortex activity during esophageal
      stimulation, suggesting a sensitized esophago-cortical neuraxis. However,
      information regarding the functional connectivity (FC) of the insula during
      visceral stimulation is lacking. The primary aim of this study was to investigate
      the FC of insular subregions during esophageal acid stimulation. METHODS:
      Functional imaging data were obtained from 12 GERD patients and 14 healthy
      subjects during four steady state conditions: (i) presence of transnasal
      esophageal catheter (pre-infusion); (ii) neutral solution; (iii) acid infusion;
      (iv) presence of transnasal esophageal catheter following infusions (post
      infusion). The insula was parcellated into six regions of interest. FC maps
      between each insular ROI and interoceptive regions were created. Differences in
      FC between GERD patients and healthy subjects were determined across the 4 study
      conditions. KEY RESULTS: All GERD patients experienced heartburn during and after
      esophageal acidification. Significant differences between GERD patients and
      healthy subjects were seen in: (i) insula-thalamic FC (neutral solution infusion,
      acid infusion, post-infusion); (ii) insula-amygdala FC (acid infusion, post
      infusion); (iii) insula-hippocampus and insula-cingulate FC (post-infusion).
      CONCLUSIONS & INFERENCES: Esophageal stimulation in GERD patients revealed
      significant insular cortex FC differences with regions involved in
      viscerosensation and interoception. The results of our study provide further
      evidence that the insula, located at the transition of afferent physiologic
      information to human feelings, is essential for both visceral homeostasis and the
      experience of heartburn in GERD patients.

PMID- 25367278
TI  - Effects of clinical mastitis on reproductive and milk performance of Holstein
      cows in Morocco.
AB  - The aim of this study was to determine the influence of clinical mastitis and
      time of first mastitis occurrence on reproductive and milk performance of
      Holstein cows. Data were collected in a dairy farm from 2008 to 2012 on 1725
      cows, among which 464 cows with mastitis. To determine the influence of clinical
      mastitis on reproductive and milk performance, models included fixed effects of
      parity, calving season, calving year, and group (cows with and with no mastitis).
      To determine the effect of time of 1st mastitis occurrence on reproductive
      performance, the mastitic cows group was further reclassified into three groups:
      prior to 60 days, between 60 and 90 days and greater than 90 days postpartum. For
      milk performance, the mastitic cows group was divided into two groups: before and
      after peak milk yield. Clinical mastitis had significant effects on calving to
      first AI interval, milk yield, and fat yield, but a non-significant effect on
      days open, number of inseminations per conception, and milk fat percentage.
      Mastitic cows had a calving to first AI interval 6.1 days longer and 549.6 kg
      milk and 20.4 kg fat per 305 days of lactation lower than those with no mastitis.
      Time of 1st mastitis occurrence did not have any significant effect on
      reproductive performance. Further, milk and fat yields of cows diseased before
      peak milk yield were 506 kg and 23.9 kg, respectively, lower than those of cows
      affected after peak milk yield. Extra attention needs to be paid to mastitis
      during the early postpartum period.

PMID- 25367279
TI  - Intake, performance, and efficiency of nutrient utilization in Saanen goat kids
      fed diets containing calcium salts of fatty acids.
AB  - The objective of this study was to evaluate the effect of feeding Saanen goat
      kids with calcium salts of fatty acids (CSFA) in diet, on intake, performance,
      digestibility of nutrients, and blood parameters. Twenty-eight uncastrated male
      goat kids, with round average age to 112.86 +/- 4.81 days and an average body
      weight (BW) of 19.54 +/- 2.76 kg, were distributed in a completely randomized
      design distributed into four groups with seven animals per group: one control
      group fed a diet containing 2.5 Mcal metabolizable energy (ME)/kg dry matter (DM)
      and three groups fed a diet containing 2.6, 2.7, or 2.8 Mcal ME/kg DM, with CSFA
      added to increase the energy levels. The animals were fed the diets until they
      reached an average BW of 28 kg. There was hardly any apparent effect of dietary
      CSFA on intake of DM and organic matter (OM). The digestibility of DM and OM
      showed an improvement with 2.64 and 2.65 Mcal ME/kg DM in the diet. The diets
      containing CSFA improved average daily gain and reduced the time on the feedlot
      to 30 days fed diet with 2.8 Mcal ME/kg DM. However, lipid supplementation
      increased serum cholesterol levels. Thus, CSFA can be used to increase the energy
      density of the diet in finisher Saanen goat kids and improve performance by
      reducing days on feedlot. 

PMID- 25367280
TI  - Effect of intravaginal fluorogestone acetate sponges on prolactin levels of
      Damascus-local cross breed goats.
AB  - The effect of intravaginal fluorogestone acetate (FGA) sponges on prolactin
      levels (PRL) and correlations between PRL and milk somatic cell count (SCC) and
      steroid hormones levels of Damascus-local cross goats during transitional period
      to anestrous were investigated in this study. Fifty-six goats were assigned to
      three groups. Group 1 (FGA, n = 19) was treated with 40 mg FGA and equine
      chorionic gonadotropin (600 IU, i.m.) at time of sponge withdrawal (day 0). Group
      2 (FGA-PGF; n = 19) was treated similar to group 1 but was also injected with
      dinoprost tromethamine (naturally occurring PGF2alpha) (10 mg, i.m.) on day 0.
      Control goats (n = 18) were left untreated. On day 0, five fertile bucks were
      turned in with all goats. Milk and blood samples were collected on days -13 (day
      of sponge insertion), -6, 0, 1, 2, 7, 13, and 20. Prolactin levels were at lowest
      values on day -13 of the study and increased (p < 0.05) from day -6 to day 20 in
      all groups. A significant positive correlation (p < 0.05) between PRL and
      progesterone and between PRL and estradiol levels was found in this study. No
      significant correlation was found between PRL and SCC of all groups during the
      study except on days 2 and 20 where PRL levels were correlated (p < 0.05) with
      SCC of left udder halves of FGA group. In conclusion, estrus induction with FGA
      resulted in significant increase in PRL. A positive correlation was found between
      PRL and steroid hormones, but there was no correlation between PRL and goat milk
      SCC. 

PMID- 25367281
TI  - Functional disability in late-middle-aged and older adults admitted to a safety
      net hospital.
AB  - OBJECTIVES: To determine the prevalence of preadmission functional disability in
      late-middle-aged and older safety-net inpatients and to identify characteristics
      associated with functional disability by age. DESIGN: Cross-sectional analysis.
      SETTING: Safety-net hospital in San Francisco, California. PARTICIPANTS: English
      , Spanish-, and Chinese-speaking community-dwelling individuals aged 55 and older
      admitted to a safety-net hospital with anticipated return to the community (N =
      699). MEASUREMENTS: At hospital admission, participants reported their need for
      help performing five activities of daily living (ADLs) and seven instrumental
      activities of daily living (IADLs) 2 weeks before admission. ADL disability was
      defined as needing help performing one or more ADLs and IADL disability as
      needing help performing two or more IADLs. Participant characteristics were
      assessed, including sociodemographic characteristics, health status, health
      related behaviors, and health-seeking behaviors. RESULTS: Overall, 28.3% of
      participants reported that they had an ADL disability 2 weeks before admission,
      and 40.4% reported an IADL disability. The prevalence of preadmission ADL
      disability was 28.9% of those aged 55 to 59, 20.7% of those aged 60 to 69, and
      41.2% of those aged 70 and older (P < .001). The prevalence of IADL disability
      had a similar distribution. The characteristics associated with functional
      disability differed according to age; in participants aged 55 to 59, African
      Americans had a higher odds of ADL and IADL disability, whereas in participants
      aged 60 to 69 and aged 70 and older, inadequate health literacy was associated
      with functional disability. CONCLUSION: Preadmission functional disability is
      common in individuals aged 55 and older admitted to a safety-net hospital. Late
      middle-aged individuals admitted to safety-net hospitals may benefit from models
      of acute care currently used for older adults that prevent adverse outcomes
      associated with functional disability.

PMID- 25367282
TI  - Sibling similarity in family formation.
AB  - Sibling studies have been widely used to analyze the impact of family background
      on socioeconomic and, to a lesser extent, demographic outcomes. We contribute to
      this literature with a novel research design that combines sibling comparisons
      and sequence analysis to analyze longitudinal family-formation trajectories of
      siblings and unrelated persons. This allows us to scrutinize in a more rigorous
      way whether sibling similarity exists in family-formation trajectories and
      whether siblings' shared background characteristics, such as parental education
      and early childhood family structure, can account for similarity in family
      formation. We use Finnish register data from 1987 through 2007 to construct
      longitudinal family-formation trajectories in young adulthood for siblings and
      unrelated dyads (N = 14,257 dyads). Findings show that family formation is
      moderately but significantly more similar for siblings than for unrelated dyads,
      also after controlling for crucial parental background characteristics. Shared
      parental background characteristics add surprisingly little to account for
      sibling similarity in family formation. Instead, gender and the respondents' own
      education are more decisive forces in the stratification of family formation.
      Yet, family internal dynamics seem to reinforce this stratification such that
      siblings have a higher probability to experience similar family-formation
      patterns. In particular, patterns that correspond with economic disadvantage are
      concentrated within families. This is in line with a growing body of research
      highlighting the importance of family structure in the reproduction of social
      inequality. 

PMID- 25367283
TI  - The rice (Oryza sativa L.) LESION MIMIC RESEMBLING, which encodes an AAA-type
      ATPase, is implicated in defense response.
AB  - Lesion mimic mutants (LMMs) provide a useful tool to study defense-related
      programmed cell death (PCD) in plants. Although a number of LMMs have been
      identified in multiple species, most of the candidate genes are yet to be
      isolated. Here, we report the identification and characterization of a novel rice
      (Oryza sativa L.) lesion mimic resembling (lmr) mutant, and cloning of the
      corresponding LMR gene. The LMR locus was initially delineated to 1.2 Mb region
      on chromosome 6, which was further narrowed down to 155-kb using
      insertions/deletions (INDELs) and cleavage amplified polymorphic sequence markers
      developed in this study. We sequenced the open reading frames predicted within
      the candidate genomic region, and identified a G-A base substitution causing a
      premature translation termination in a gene that encodes an ATPase associated
      with various cellular activities type (AAA-type) protein. RNA interference
      transgenic lines with reduced LMR transcripts exhibited the lesion mimic
      phenotype similar to that of lmr plants. Furthermore, expression of the wild-type
      LMR in the mutant background complemented the lesion phenotype, confirming that
      the mutation identified in LMR is responsible for the mutant phenotype. The
      pathogenesis-related (PR) genes PBZ1 and PR1 were induced in lmr, which also
      showed enhanced resistance to rice blast (Magnaporthe oryzae) and bacterial
      blight (Xanthomonas oryzae pv. oryzae), suggesting LMR is a negative regulator of
      cell death in rice. The identification of lmr and cloning of the corresponding
      LMR gene provide an additional resource for the study of PCD in plants. 

PMID- 25367284
TI  - Life cycle assessment of bioethanol production from woodchips with modifications
      in the pretreatment process.
AB  - Pretreatment as a crucial step in the process of ethanol production has
      significant influences on the process efficiency and on the environmental
      performance of the bioethanol production from lignocellulosic biomass. In present
      life cycle analysis (LCA) study, two cases for pretreatment of woodchips were
      considered as the focal point of the ethanol plant. One was assumed as base
      scenario whereas the second is the proposed alternative by implementation of
      modifications on the base design. In the first stage, LCA results of pretreatment
      unit showed lower environmental impacts in respiratory inorganics and land use
      than in new scenario, while the base scenario revealed better performance in
      fossil fuels. The results of the second stage of LCA study demonstrated
      improvement in proposed design in most categories of environmental impacts such
      as 18.5 % in land use as well as 17 % improvement in ecosystem quality.

PMID- 25367285
TI  - Biochemical, kinetic, and in silico characterization of DING protein purified
      from probiotic lactic acid bacteria Pediococcus acidilactici NCDC 252.
AB  - DING proteins are intriguing proteins characterized by conserved N-terminal
      sequence. In spite of unusually high sequence conservation even between distantly
      related species, DING proteins exhibit outstanding functional diversity. An
      extracellular caseinolytic alkaline enzyme was purified to homogeneity from a
      probiotic lactic acid bacteria Pediococcus acidilactici NCDC 252 using a simple
      procedure involving ammonium sulphate precipitation and gel filtration
      chromatography. This was purified 45.72-fold with a yield and specific activity
      of 43.5 % and 250 U/mg, respectively. The calculated molecular weight was 38.7
      and 38.9 kDa by MALDI and SDS-PAGE, respectively, and pI was 7.77. The enzyme
      exhibited optimal activity at pH 8.0 and 40  degrees C. It was considerably
      stable up to pH 12. For casein, the enzyme had K m of 20 MUM with V max of 26
      U/ml. The enzyme was resistant to organic solvents but sensitive to DTNB and EDTA
      that confirmed it as thiol protein with involvement of metal ions in catalysis.
      Its tryptic peptide fragments showed 95 % similarity with eukaryotic DING, i.e.,
      human phosphate binding protein (HPBP). Homology-based structure evaluation using
      HBPB as template revealed both to be structurally conserved and also possessing
      conserved phosphate binding motifs.

PMID- 25367286
TI  - Alteration of gene expression profiling including GPR174 and GNG2 is associated
      with vasovagal syncope.
AB  - Vasovagal syncope (VVS) causes accidental harm for susceptible patients. However,
      pathophysiology of this disorder remains largely unknown. In an effort to
      understanding of molecular mechanism for VVS, genome-wide gene expression
      profiling analyses were performed on VVS patients at syncope state. A total of 66
      Type 1 VVS child patients and the same number healthy controls were enrolled in
      this study. Peripheral blood RNAs were isolated from all subjects, of which 10
      RNA samples were randomly selected from each groups for gene expression profile
      analysis using Gene ST 1.0 arrays (Affymetrix). The results revealed that 103
      genes were differently expressed between the patients and controls.
      Significantly, two G-proteins related genes, GPR174 and GNG2 that have not been
      related to VVS were among the differently expressed genes. The microarray results
      were confirmed by qRT-PCR in all the tested individuals. Ingenuity pathway
      analysis and gene ontology annotation study showed that the differently expressed
      genes are associated with stress response and apoptosis, suggesting that the
      alteration of some gene expression including G-proteins related genes is
      associated with VVS. This study provides new insight into the molecular mechanism
      of VVS and would be helpful to further identify new molecular biomarkers for the
      disease. 

PMID- 25367287
TI  - ZEB1 as an indicator of tumor recurrence for areca quid chewing-associated oral
      squamous cell carcinomas.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth most prevalent
      malignancy worldwide and the third most common cancer in developing nation. Most
      OSCC patients relapse within months after receiving treatment. Therefore,
      searching the biomarkers of recurrence is urgently required to improve OSCC
      patient survival. METHODS: We set out to explore whether expression of ZEB1 could
      be triggered in oral epithelial cells (SG and FaDu) by arecoline in vitro.
      Control and ZEB1-knockdown arecoline-stimulated SG and FaDu were subjected to
      migration/invasiveness/anchorage-independent growth assay. Primary and recurrent
      OSCC tissues from areca quid chewers were analyzed using real-time RT-PCR
      analysis for ZEB1 expression. RESULTS: Arecoline led to dose-dependent elevation
      of ZEB1 expression in SG and FaDu cells. Downregulation of ZEB1 by lentiviral
      infection significantly reversed arecoline-induced oncogenicity including
      migration ability, cell invasiveness, and anchorage-independent growth in SG and
      FaDu cells. Clinically, the level of ZEB1 expression was higher in recurrent OSCC
      tumor samples but lower in primary lesions. CONCLUSIONS: Targeting ZEB1 might
      offer a new strategy for the treatment of OSCC patients. ZEB1 can serve as a
      progression and relapse marker in OSCC patients.

PMID- 25367288
TI  - Arsenic induces diabetic effects through beta-cell dysfunction and increased
      gluconeogenesis in mice.
AB  - Arsenic as a potential risk factor for type 2 diabetes has been received
      attention recently. However, the roles of arsenic on development of diabetes are
      unclear. In this study, we compared the influences of inorganic arsenic (iAs) on
      normal and diabetic mice by systems toxicology approaches. Although iAs exposure
      did not change glucose tolerance in normal mice, it caused the pancreatic beta
      cell dysfunction and increased gluconeogenesis and oxidative damages in liver.
      However, iAs exposure worsened the glucose tolerance in diabetic mice, which
      might be due to increased gluconeogenesis and impairment of pancreatic beta-cell
      function. It is interesting that iAs exposure could improve the insulin
      sensitivity based on the insulin tolerance testing by the activation of glucose
      uptake-related genes and enzymes in normal and diabetic individuals. Our data
      suggested that iAs exposure could cause pre-diabetic effects by altering the
      lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and
      worsen diabetic effects in diabetes individual by these processes. Insulin
      resistance might be not the reason of diabetic effects caused by iAs, indicating
      that mechanism of the diabetogenic effects of iAs exposure is different from the
      mechanism associated with traditional risk factors (such as obesity)-reduced type
      2 diabetes. 

PMID- 25367289
TI  - Catalyst engineering for lithium ion batteries: the catalytic role of Ge in
      enhancing the electrochemical performance of SnO2(GeO2)0.13/G anodes.
AB  - The catalytic role of germanium (Ge) was investigated to improve the
      electrochemical performance of tin dioxide grown on graphene (SnO(2)/G)
      nanocomposites as an anode material of lithium ion batteries (LIBs). Germanium
      dioxide (GeO(20) and SnO(2) nanoparticles (<10 nm) were uniformly anchored on the
      graphene sheets via a simple single-step hydrothermal method. The synthesized
      SnO(2)(GeO(2))0.13/G nanocomposites can deliver a capacity of 1200 mA h g(-1) at
      a current density of 100 mA g(-1), which is much higher than the traditional
      theoretical specific capacity of such nanocomposites (~ 702 mA h g(-1)). More
      importantly, the SnO(2)(GeO(2))0.13/G nanocomposites exhibited an improved rate,
      large current capability (885 mA h g(-1) at a discharge current of 2000 mA g(-1))
      and excellent long cycling stability (almost 100% retention after 600 cycles).
      The enhanced electrochemical performance was attributed to the catalytic effect
      of Ge, which enabled the reversible reaction of metals (Sn and Ge) to metals
      oxide (SnO(2) and GeO(2)) during the charge/discharge processes. Our demonstrated
      approach towards nanocomposite catalyst engineering opens new avenues for next
      generation high-performance rechargeable Li-ion batteries anode materials.

PMID- 25367290
TI  - Mycobacterium mucogenicum infections in immunocompromised hosts.

PMID- 25367291
TI  - Ambulatory electrocardiographic monitoring between artifacts and
      misinterpretation, management errors of commission and errors of omission.
AB  - BACKGROUND: The aim of the study is to contrast the role of conventional
      ambulatory electrocardiographic monitoring (AEM) artifacts with a less emphasized
      problem with potentially more serious implications, that is, the failure to
      recognize, and therefore misinterpret, a genuine arrhythmia episode in the AEM
      recording. METHODS: The study material included 500 Holter recordings and 500
      recordings from the cardiac telemetry unit. RESULTS: Electrocardiographic (ECG)
      artifacts were more common in telemetry recordings (5.6%) compared to Holter
      recordings (4%) for a total of 4.8%. There were 35 examples of misinterpretation
      of AEM recordings (3.5%). These were significantly more common in telemetry
      recordings (2.6%) compared to Holter recordings (0.9%). The most common ECG
      artifacts were examples of pseudo ventricular tachyarrhythmia (VT). The majority
      of misinterpretation (26 of 35 examples) were fast supraventricular
      tachyarrhythmias with aberrant QRS (including six examples of atrial flutter with
      periods of 1:1 atrioventricular conduction) that were misdiagnosed as ventricular
      VT. Other examples were misinterpretation of arrhythmic episodes consistent with
      sick sinus syndrome, pacemaker malfunction, and long QT syndrome. Only 5 of 48
      examples of AEM artifacts resulted in management errors of commission or errors
      of omission compared to all 35 examples of misinterpretation. CONCLUSIONS:
      Compared to conventional artifacts in AEM, misinterpretation of nonartifactual
      arrhythmic episodes consistently resulted in management errors. Misinterpretation
      was significantly more common with telemetry recordings compared to Holter ECG.
      This highlights the need for more appropriate training of the entire clinical
      team in charge of the management of the cardiac telemetry unit.

PMID- 25367292
TI  - Conservation genetics of a threatened butterfly: comparison of allozymes, RAPDs
      and microsatellites.
AB  - BACKGROUND: Addressing genetic issues in the management of fragmented wild
      populations of threatened species is one of the most important challenges in
      conservation biology. Nowadays, a diverse array of molecular methods exists to
      assess genetic diversity and differentiation of wild populations such as
      allozymes, dominant markers and co-dominant markers. However it remains
      worthwhile i) to compare the genetic estimates obtained using those several
      markers in order to ii) test their relative utility, reliability and relevance
      and iii) the impact of these results for the design of species-specific
      conservation measures. RESULTS: Following the successful isolation of 15
      microsatellites loci for the cranberry fritillary butterfly, Boloria aquilonaris,
      we analyzed the genetic diversity and structure of eight populations located in
      four different landscapes, at both the regional and the landscape scales. We
      confront results based on microsatellites to those obtained using allozymes and
      RAPDs on the same samples. Genetic population analyses using different molecular
      markers indicate that the B. aquilonaris populations are characterized by a weak
      genetic variation, likely due to low effective population size and low dispersal
      at the regional scale. This results in inbreeding in some populations, which may
      have detrimental consequences on their long term viability. However, gene flow
      within landscape is limited but not inexistent, with some long range movements
      resulting in low or no isolation by distance. Spatial structuring was detected
      among the most isolated populations. CONCLUSIONS: The use of allozymes and RAPD
      are of very limited value to determine population structuring at small spatial
      (i.e. landscape) scales, microsatellites giving much higher estimate resolution.
      The use of RAPD data is also limited for evidencing inbreeding. However, coarse
      grain spatial structure (i.e. regional scale), and gene flow estimates based on
      RAPD and microsatellites data gave congruent results. At a time with increasing
      development of new molecular methods and markers, dominant markers may still be
      worthwhile to consider in organisms for which no genomic information is
      available, and for which limited resources are available.

PMID- 25367293
TI  - Violation of the 12/23 rule of genomic V(D)J recombination is common in
      lymphocytes.
AB  - V(D)J genomic recombination joins single gene segments to encode an extensive
      repertoire of antigen receptor specificities in T and B lymphocytes. This process
      initiates with double-stranded breaks adjacent to conserved recombination signal
      sequences that contain either 12- or 23-nucleotide spacer regions. Only
      recombination between signal sequences with unequal spacers results in productive
      coding genes, a phenomenon known as the "12/23 rule." Here we present two novel
      genomic tools that allow the capture and analysis of immune locus rearrangements
      from whole thymic and splenic tissues using second-generation sequencing.
      Further, we provide strong evidence that the 12/23 rule of genomic recombination
      is frequently violated under physiological conditions, resulting in unanticipated
      hybrid recombinations in ~10% of Tcra excision circles. Hence, we demonstrate
      that strict adherence to the 12/23 rule is intrinsic neither to recombination
      signal sequences nor to the catalytic process of recombination and propose that
      nonclassical excision circles are liberated during the formation of antigen
      receptor diversity. 

PMID- 25367294
TI  - Genome-wide analysis of local chromatin packing in Arabidopsis thaliana.
AB  - The spatial arrangement of interphase chromosomes in the nucleus is important for
      gene expression and genome function in animals and in plants. The recently
      developed Hi-C technology is an efficacious method to investigate genome packing.
      Here we present a detailed Hi-C map of the three-dimensional genome organization
      of the plant Arabidopsis thaliana. We find that local chromatin packing differs
      from the patterns seen in animals, with kilobasepair-sized segments that have
      much higher intrachromosome interaction rates than neighboring regions,
      representing a dominant local structural feature of genome conformation in A.
      thaliana. These regions, which appear as positive strips on two-dimensional
      representations of chromatin interaction, are enriched in epigenetic marks
      H3K27me3, H3.1, and H3.3. We also identify more than 400 insulator-like regions.
      Furthermore, although topologically associating domains (TADs), which are
      prominent in animals, are not an obvious feature of A. thaliana genome packing,
      we found more than 1000 regions that have properties of TAD boundaries, and a
      similar number of regions analogous to the interior of TADs. The insulator-like,
      TAD-boundary-like, and TAD-interior-like regions are each enriched for distinct
      epigenetic marks and are each correlated with different gene expression levels.
      We conclude that epigenetic modifications, gene density, and transcriptional
      activity combine to shape the local packing of the A. thaliana nuclear genome. 

PMID- 25367295
TI  - Structural basis for ion selectivity revealed by high-resolution crystal
      structure of Mg2+ channel MgtE.
AB  - Magnesium is the most abundant divalent cation in living cells and is crucial to
      several biological processes. MgtE is a Mg(2+) channel distributed in all domains
      of life that contributes to the maintenance of cellular Mg(2+) homeostasis. Here
      we report the high-resolution crystal structures of the transmembrane domain of
      MgtE, bound to Mg(2+), Mn(2+) and Ca(2+). The high-resolution Mg(2+)-bound
      crystal structure clearly visualized the hydrated Mg(2+) ion within its
      selectivity filter. Based on those structures and biochemical analyses, we
      propose a cation selectivity mechanism for MgtE in which the geometry of the
      hydration shell of the fully hydrated Mg(2+) ion is recognized by the side-chain
      carboxylate groups in the selectivity filter. This is in contrast to the K(+)
      selective filter of KcsA, which recognizes a dehydrated K(+) ion. Our results
      further revealed a cation-binding site on the periplasmic side, which regulate
      channel opening and prevents conduction of near-cognate cations. 

PMID- 25367296
TI  - Differences in embryo quality are associated with differences in oocyte
      composition: a proteomic study in inbred mice.
AB  - Current models of early mouse development assign roles to stochastic processes
      and epigenetic regulation, which are considered to be as influential as the
      genetic differences that exist between strains of the species Mus musculus. The
      aim of this study was to test whether mouse oocytes vary from each other in the
      abundance of gene products that could influence, prime, or even predetermine
      developmental trajectories and features of derivative embryos. Using the paradigm
      of inbred mouse strains, we quantified 2010 protein groups (SILAC LC-MS/MS) and
      15205 transcripts (RNA deep sequencing) present simultaneously in oocytes of four
      strains tested (129/Sv, C57Bl/6J, C3H/HeN, DBA/2J). Oocytes differed according to
      donor strain in the abundance of catalytic and regulatory proteins, as confirmed
      for a subset (bromodomain adjacent to zinc finger domain, 1B [BAZ1B], heme
      oxygenase 1 [HMOX1], estrogen related receptor, beta [ESRRB]) via
      immunofluorescence in situ. Given a Pearson's r correlation coefficient of 0.18
      0.20, the abundance of oocytic proteins could not be predicted from that of
      cognate mRNAs. Our results document that a prerequisite to generate embryo
      diversity, namely the different abundances of maternal proteins in oocytes, can
      be studied in the model of inbred mouse strains. Thus, we highlight the
      importance of proteomic quantifications in modern embryology. All MS data have
      been deposited in the ProteomeXchange with identifier PXD001059
      (http://proteomecentral.proteomexchange.org/dataset/PXD001059). 

PMID- 25367298
TI  - Multispecific Aspergillus T cells selected by CD137 or CD154 induce protective
      immune responses against the most relevant mold infections.
AB  - BACKGROUND: Aspergillus and Mucorales species cause severe infections in patients
      after hematopoietic stem cell transplantation (HSCT). Induction of antifungal
      CD4(+) T-helper type 1 (Th1) immunity is an appealing strategy to combat these
      infections. Immunotherapeutic approaches are so far limited because of a lack of
      antigens inducing protective T cells, their elaborate production, and the need of
      targeting a broad spectrum of pathogenic fungi. METHODS: We examined the response
      to different Aspergillus fumigatus proteins in healthy individuals and patients
      after HSCT and compared rapid selection protocols for fungus-specific T cells
      based on CD137 or CD154 expression. RESULTS: The A. fumigatus proteins Crf1,
      Gel1, and Pmp20 induced strong Th1 responses in healthy individuals. T cells
      specific for these antigens expanded in patients with active invasive
      aspergillosis, indicating their contribution to infection control. Th1 cells
      specific for the 3 proteins can be selected with similar specificity within 24
      hours, based on CD137 or CD154 expression. These cells recognize naturally
      processed A. fumigatus and the multispecific T-cell lines, directed against all 3
      proteins, especially those selected by CD154, additionally cross-react to
      different Aspergillus and Mucorales species. CONCLUSIONS: These findings may form
      the basis for adoptive T-cell transfer for prophylaxis or treatment in patients
      with these devastating infections.

PMID- 25367297
TI  - Prolonged proinflammatory cytokine production in monocytes modulated by
      interleukin 10 after influenza vaccination in older adults.
AB  - We evaluated in vivo innate immune responses in monocyte populations from 67
      young (aged 21-30 years) and older (aged >=65 years) adults before and after
      influenza vaccination. CD14(+)CD16(+) inflammatory monocytes were induced after
      vaccination in both young and older adults. In classical CD14(+)CD16(-) and
      inflammatory monocytes, production of tumor necrosis factor alpha and interleukin
      6, as measured by intracellular staining, was strongly induced after vaccination.
      Cytokine production was strongly associated with influenza vaccine antibody
      response; the highest levels were found as late as day 28 after vaccination in
      young subjects and were substantially diminished in older subjects. Notably,
      levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were markedly
      elevated in monocytes from older subjects before and after vaccination. In
      purified monocytes, we found age-associated elevation in phosphorylated signal
      transducer and activator of transcription-3, and decreased serine 359
      phosphorylation of the negative IL-10 regulator dual-specificity phosphatase 1.
      These findings for the first time implicate dysregulated IL-10 production in
      impaired vaccine responses in older adults. 

PMID- 25367299
TI  - Nonstructural protein 1 (NS1)-mediated inhibition of c-Abl results in acute lung
      injury and priming for bacterial co-infections: insights into 1918 H1N1 pandemic?
AB  - BACKGROUND: Nonstructural protein 1 (NS1) proteins from avian influenza viruses
      like the 1918 pandemic NS1 are capable of inhibiting the key signaling integrator
      c-Abl (Abl1), resulting in massive cytopathic cell alterations. METHODS: In the
      current study, we addressed the consequences of NS1-mediated alteration of c-Abl
      on acute lung injury and pathogenicity in an in vivo mouse model. RESULTS:
      Comparing isogenic strains that differ only in their ability to inhibit c-Abl, we
      observed elevated pathogenicity for the c-Abl-inhibiting virus. NS1-mediated
      blockade of c-Abl resulted in severe lung pathology and massive edema formation
      and facilitated secondary bacterial pneumonia. This phenotype was independent of
      differences in replication and immune responses, defining it as an NS1 virulence
      mechanism distinct from its canonical functions. Microarray analysis revealed
      extensive downregulation of genes involved in cell integrity and vascular
      endothelial regulation. CONCLUSIONS: NS1 protein-mediated blockade of c-Abl
      signaling drives acute lung injury and primes for bacterial coinfections
      revealing potential insights into the pathogenicity of the 1918 pandemic virus.

PMID- 25367300
TI  - K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan
      Africa.
AB  - Mutations in the Plasmodium falciparum K13-propeller domain have recently been
      shown to be important determinants of artemisinin resistance in Southeast Asia.
      This study investigated the prevalence of K13-propeller polymorphisms across sub
      Saharan Africa. A total of 1212 P. falciparum samples collected from 12 countries
      were sequenced. None of the K13-propeller mutations previously reported in
      Southeast Asia were found, but 22 unique mutations were detected, of which 7 were
      nonsynonymous. Allele frequencies ranged between 1% and 3%. Three mutations were
      observed in >1 country, and the A578S was present in parasites from 5 countries.
      This study provides the baseline prevalence of K13-propeller mutations in sub
      Saharan Africa. 

PMID- 25367305
TI  - Geographic and temporal trends in frontal sinus surgery.
AB  - BACKGROUND: The purpose of this study was to evaluate geographic and temporal
      trends in frontal sinus surgery procedures. METHODS: Medicare Part B data files
      from 2000 to 2011 were examined for temporal trends in various frontal sinus
      procedures, and the most recent year containing geographic information (2010) was
      evaluated for Current Procedural Terminology (CPT) code use. Additionally,
      nationwide charges per procedure were recorded. Regional populations of
      individuals >= 65 years old were obtained from the 2010 U.S. Census, and surgical
      society websites were used to determine the number of practicing rhinologists and
      otolaryngologists in each region. RESULTS: The use of open approaches declined by
      one third, while endoscopic procedures went from 6463 to 19262 annually, with the
      most marked increases occurring from 2006 through 2011. Geographic variation was
      noted, with practitioners in the South Atlantic states performing the greatest
      number of endoscopic procedures in 2010, whereas the East South Central states
      had the greatest number when controlling for population. There was an inverse
      relationship between endoscopic procedures performed and number of fellowship
      trained rhinologists (controlling for regional populations) (R(2) = 0.66). The
      first year frontal sinus ballooning had a unique CPT code illustrated decreased
      reimbursements for non-balloon endoscopic surgery ($609) relative to balloon
      approaches ($2635). CONCLUSION: Declines in open frontal sinus surgery and marked
      increases in endoscopic approaches have potential implications for residency
      training. Potential reasons for marked increases in endoscopic approaches include
      the rising popularity of balloon technologies, although this is speculative.
      Geographic variation exists in frontal sinus surgery patterns, including an
      inverse relationship between endoscopic approaches and the number of fellowship
      trained rhinologists.

PMID- 25367306
TI  - Towards a better understanding of Apis mellifera and Varroa destructor
      microbiomes: introducing 'phyloh' as a novel phylogenetic diversity analysis
      tool.
AB  - The study of diversity in biological communities is an intriguing field. Huge
      amount of data are nowadays available (provided by the innovative DNA sequencing
      techniques), and management, analysis and display of results are not trivial.
      Here, we propose for the first time the use of phylogenetic entropy as a measure
      of bacterial diversity in studies of microbial community structure. We then
      compared our new method (i.e. the web tool phyloh) for partitioning phylogenetic
      diversity with the traditional approach in diversity analyses of bacteria
      communities. We tested phyloh to characterize microbiome in the honeybee (Apis
      mellifera, Insecta: Hymenoptera) and its parasitic mite varroa (Varroa
      destructor, Arachnida: Parasitiformes). The rationale is that the comparative
      analysis of honeybee and varroa microbiomes could open new perspectives
      concerning the role of the parasites on honeybee colonies health. Our results
      showed a dramatic change of the honeybee microbiome when varroa occurs,
      suggesting that this parasite is able to influence host microbiome. Among the
      different approaches used, only the entropy method, in conjunction with
      phylogenetic constraint as implemented in phyloh, was able to discriminate varroa
      microbiome from that of parasitized honeybees. In conclusion, we foresee that the
      use of phylogenetic entropy could become a new standard in the analyses of
      community structure, in particular to prove the contribution of each biological
      entity to the overall diversity. 

PMID- 25367307
TI  - Dendritic silica particles with center-radial pore channels: promising platforms
      for catalysis and biomedical applications.
AB  - Dendritic silica micro-/nanoparticles with center-radial pore structures, a kind
      of newly created porous material, have attracted considerable attention owing to
      their unique open three-dimensional dendritic superstructures with large pore
      channels and highly accessible internal surface areas compared with conventional
      mesoporous silica nanoparticles (MSNs). They are very promising platforms for a
      variety of applications in catalysis and nanomedicine. In this review, their
      unique structural characteristics and properties are first analyzed, then novel
      and interesting synthesis methods associated with the possible formation
      mechanisms are summarized to provide material scientists some inspiration for the
      preparation of this kind of dendritic particles. Subsequently, a few examples of
      interesting applications are presented, mainly in catalysis, biomedicine, and
      other important fields such as for sacrificial templates and functional coatings.
      The review is concluded with an outlook on the prospects and challenges in terms
      of their controlled synthesis and potential applications.

PMID- 25367308
TI  - Carotenoids concentration of Gac (Momordica cochinchinensis Spreng.) fruit oil
      using cross-flow filtration technology.
AB  - Gac (Momordica cochinchinensis Spreng.) fruit, a traditional fruit in Vietnam and
      other countries of eastern Asia, contains an oil rich in carotenoids, especially
      lycopene and beta-carotene. Carotenoids in gac fruit oil were concentrated using
      cross-flow filtration. In total recycle mode, effect of membrane pore size,
      temperature, and transmembrane pressure (TMP) on permeate flux and on retention
      coefficients has been exploited. Resistance of membrane, polarization
      concentration, and fouling were also analyzed. Optimum conditions for a high
      permeate flux and a good carotenoids retention are 5 nm, 2 bars, and 40  degrees
      C of membrane pore size, TMP, and temperature, respectively. In batch mode,
      retentate was analyzed through index of acid, phospholipids, total carotenoids
      content (TCC), total antioxidant activity, total soluble solids, total solid
      content, color measurement, and viscosity. TCC in retentate is higher 8.6 times
      than that in feeding oil. Lipophilic antioxidant activities increase 6.8 times,
      while hydrophilic antioxidant activities reduce 40%. The major part of total
      resistance is due to polarization (55%) while fouling and intrinsic membrane
      contribute about 30% and 24%, respectively. 

PMID- 25367309
TI  - ATP-citrate lyase regulates cellular senescence via an AMPK- and p53-dependent
      pathway.
AB  - ATP citrate lyase (ACLY) is a key enzyme that is involved in de novo lipogenesis
      by catalyzing conversion of cytosolic citrate into acetyl CoA and oxaloacetate.
      Up-regulation of ACLY in various types of tumors enhances fatty acid synthesis
      and supplies excess acetyl CoA for histone acetylation. However, there is
      evidence that its enzymatic activity alone is insufficient to explain ACLY
      silencing-mediated growth arrest in tumor cells. In this study, we found that
      ACLY knockdown in primary human cells triggers cellular senescence and activation
      of tumor suppressor p53. Provision of acetyl CoA to ACLY knockdown cells did not
      alleviate ACLY silencing-induced p53 activation, suggesting an independent role
      for ACLY activity. Instead, ACLY physically interacted with the catalytic subunit
      of AMP-activated protein kinase (AMPK) and inhibited AMPK activity. The
      activation of AMPK under ACLY knockdown conditions may lead to p53 activation,
      ultimately leading to cellular senescence. In cancer cells, ACLY silencing
      induced p53 activation facilitated DNA damage-induced cell death. Taken together,
      our results suggest a novel function of ACLY in cellular senescence and
      tumorigenesis.

PMID- 25367310
TI  - Impact of lowering pulmonary vascular resistance on right and left ventricular
      deformation in pulmonary arterial hypertension.
AB  - AIMS: As pulmonary arterial hypertension (PAH) is associated with significant
      morbidity and mortality, particularly among patients with right ventricular (RV)
      dysfunction, we aimed to determine the impact of therapy to reduce pulmonary
      vascular resistance (PVR) on RV and LV deformation in PAH. METHODS AND RESULTS:
      Right ventricular free wall longitudinal strain (FWLS) and LV global
      circumferential strain (CS) were measured at baseline, 12 weeks, and 24 weeks in
      68 patients with advanced PAH randomized to imatinib or placebo in the Imatinib
      in Pulmonary arterial hypertension, a Randomized Efficacy Study (IMPRES) trial,
      and compared with 30 healthy controls. Compared with controls, PAH was associated
      with impaired RV FWLS (-15.9 +/- 5.4 vs. -30.8 +/- 4.3, respectively; P < 0.0001)
      and LV septal CS (-24.2 +/- 8.2 vs. -31.4 +/- 5.3, respectively, P < 0.0001), but
      not LV global CS. Improvement in PVR and mean pulmonary artery pressure (MPAP)
      over a 24-week period was significantly associated with improvement in RV FWLS (r
      = 0.39, P = 0.02; 0.33, P = 0.04 respectively), LV global CS (r = 0.61, P =
      0.0001; r = 0.60, P = 0.0001, respectively), and LV septal CS (r = 0.50, P =
      0.005; r = 0.56, P = 0.002, respectively). These associations were most robust
      with LV global and septal CS. Imatinib therapy was associated with improvement in
      RV FWLS compared with placebo. CONCLUSIONS: PAH is associated with impaired
      biventricular deformation. Reduction in PVR is associated with improvements in
      both RV and LV deformation, coupled to improvements in MPAP and stroke volume
      index, with LV global and septal CS the strongest correlates of these changes. RV
      FWLS is sensitive to treatment effect, demonstrating greater improvement with
      imatinib compared with placebo. TRIAL REGISTRATION: NCT00902174.

PMID- 25367311
TI  - Lymphoepithelioma-like carcinoma of the urinary bladder: a case report and review
      of the literature.
AB  - BACKGROUND: Lymphoepithelioma-like carcinoma is an undifferentiated carcinoma
      with histological features similar to undifferentiated, non-keratinizing
      carcinoma of the nasopharynx. Lymphoepithelioma-like carcinoma of the urinary
      bladder is uncommon with a reported incidence of 0.3%- 1.3% of all bladder
      cancer. We report a Japanese case of predominant lymphoepithelioma-like carcinoma
      of the urinary bladder and review all of the English literature after performing
      a pooled analysis of the cases including the present one. CASE PRESENTATION: An
      83-year-old Japanese man was introduced to our department with the chief
      complaint of macroscopic hematuria. Cystoscopy demonstrated a thumb tip-sized
      bladder tumor at the trigone. The patient underwent a transurethral resection of
      the bladder tumor. The pathological examination showed predominant
      lymphoepithelioma-like carcinoma of the urinary bladder with urothelial
      carcinoma. The patient was diagnosed with muscle invasive lymphoepithelioma-like
      carcinoma of the urinary bladder and was treated with concurrent
      chemoradiotherapy. The patient is under observation with regular clinical follow
      up and remains well after 12 months, with no evidence of disease recurrence. The
      reports of 93 patients including the present one of lymphoepithelioma-like
      carcinoma of the urinary bladder from the English literature were collected
      between 1991 and 2014. Patients were evaluated for clinicopathological findings.
      Outcome resulted as follows: 59 patients (67%) did not show evidence of disease,
      14 (17%) died of disease, 5 (6%) was alive with metastases, and 9 (10%) died for
      causes unrelated to the primary disease. Cause-specific survival rate resulted
      83%. The overall patients were divided into three groups (pure, predominant and
      focal) according to the lymphoepithelioma-like carcinoma of the urinary bladder
      classification of Amin et al. CONCLUSIONS: Because lymphoepithelioma-like
      carcinoma of the urinary bladder is more sensitive to both chemotherapy and
      radiotherapy than conventional urothelial carcinoma, radical cystectomy may not
      be necessary for all patients with muscle invasive lymphoepithelioma-like
      carcinoma of the urinary bladder. Therefore, pathological information may be
      useful in selecting patients suitable for bladder-preservation treatment. On the
      other hand, the apparently more aggressive nature of focal lymphoepithelioma-like
      carcinoma of the urinary bladder suggests that these patients are probably best
      managed with radical cystectomy and adjuvant treatment.

PMID- 25367312
TI  - A green route towards highly photoluminescent and cytocompatible carbon dot
      synthesis and its separation using sucrose density gradient centrifugation.
AB  - An efficient, fast and green method for synthesis of Carbon dots (C-dots) using
      natural precursor Citrus limone under ultrasonic condition is demonstrated. Such
      as-synthesized C-dots were further purified using Sucrose density gradient
      centrifugation method (SDGC) which resulted in the separation of water-soluble,
      photo luminescent, monodispersed, highly photostable and chemically stable C-dot
      fractions (F1 and F2). They possess very small size (5-20 nm) as evidenced by
      High angle annular dark field-Scanning Transmission electron microscopy (HAADF
      STEM) and very strong luminescence as shown by fluorescence spectroscopic
      studies. Cytocompatibility and bio imaging properties of both the fractions (F1
      and F2) were then studied on Hep-2 cells. Quantum yield of F1 and F2 fraction was
      found to be 12.1 and 15 %, respectively.

PMID- 25367313
TI  - [Infectious diseases and injuries of bladder and urinary tract].
AB  - Urinary tract infections are the most common infectious diseases in Germany. In
      most cases clarification does not rely on imaging techniques other than
      sonography and is made mostly based on clinical symptoms. Computed tomography
      (CT) and magnetic resonance imaging (MRI) can be used in selected cases to find
      the cause and detection or exclusion of complications, e.g. recurrent or atypical
      and complicated courses. The method of choice for clarification of urolithiasis
      is CT. Using low-dose techniques, detection or exclusion of urinary stones can be
      achieved with a high sensitivity and specificity as well as an acceptable level
      of radiation exposure. Native stone CT supplies additional fundamental
      information that can substantially influence further therapy planning. The
      diagnosis of ureteral injuries is clinically and radiologically not trivial and
      clarification is aided by urographic contrast media. The method of CT cystography
      has an important role in the diagnostics of urinary bladder injuries. 

PMID- 25367314
TI  - Cost-effectiveness of renal denervation therapy for the treatment of resistant
      hypertension in The Netherlands.
AB  - OBJECTIVES: Safety and efficacy data for catheter-based renal denervation (RDN)
      in the treatment of resistant hypertension have been used to estimate the cost
      effectiveness of this approach. However, there are no Dutch-specific analyses.
      This study examined the cost-effectiveness of RDN from the perspective of the
      healthcare payer in The Netherlands. METHODS: A previously constructed Markov
      state-transition model was adapted and updated with costs and utilities relevant
      to the Dutch setting. The cost-effectiveness of RDN was compared with standard of
      care (SoC) for patients with resistant hypertension. The efficacy of RDN
      treatment was modeled as a reduction in the risk of cardiovascular events
      associated with a lower systolic blood pressure (SBP). RESULTS: Treatment with
      RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of
      0.89 at an additional cost of ?1315 over a patient's lifetime, resulting in a
      base case incremental cost-effectiveness ratio (ICER) of ?1474. Deterministic and
      probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy
      was cost-effective at conventional willingness-to-pay thresholds (?10,000
      80,000/QALY). CONCLUSION: RDN is a cost-effective intervention for patients with
      resistant hypertension in The Netherlands.

PMID- 25367315
TI  - Inverse finite element modeling for characterization of local elastic properties
      in image-guided failure assessment of human trabecular bone.
AB  - The local interpretation of microfinite element (MUFE) simulations plays a
      pivotal role for studying bone structure-function relationships such as failure
      processes and bone remodeling.In the past MUFE simulations have been successfully
      validated on the apparent level,however, at the tissue level validations are
      sparse and less promising. Furthermore,intra trabecular heterogeneity of the
      material properties has been shown by experimental studies. We proposed an
      inverse MUFE algorithm that iteratively changes the tissue level Young's moduli
      such that the MUFE simulation matches the experimental strain measurements.The
      algorithm is setup as a feedback loop where the modulus is iteratively adapted
      until the simulated strain matches the experimental strain. The experimental
      strain of human trabecular bone specimens was calculated from time-lapsed images
      that were gained by combining mechanical testing and synchrotron radiation
      microcomputed tomography(SRlCT). The inverse MUFE algorithm was able to iterate
      the heterogeneous distribution of moduli such that the resulting MUFE simulations
      matched artificially generated and experimentally measured strains.

PMID- 25367316
TI  - The change in eating behaviors in a Web-based weight loss program: a longitudinal
      analysis of study completers.
AB  - BACKGROUND: Eating behaviors are essential components in weight loss programs,
      but limited research has explored eating behaviors in Web-based weight loss
      programs. OBJECTIVES: The aim was to evaluate an interactive Web-based weight
      loss program on eating behaviors using the 18-item Three-Factor Eating
      Questionnaire Revised (TFEQ-R18) which measures uncontrolled eating, emotional
      eating, and cognitive restrained eating. Our Web-based weight loss program is
      comprised of information about healthy lifestyle choices, weekly chats with
      experts, social networking features, databases for recipe searches, and features
      allowing members to self-report and track their weight, physical activity, and
      dietary intake on the website. METHODS: On registering for the weight loss
      program, 23,333 members agreed to take part in the research study. The
      participants were then asked to complete the TFEQ-R18 questionnaire at baseline
      and after 3 and 6 months of participation. All data collection was conducted
      online, with no face-to-face contact. To study changes in TFEQ-R18 eating
      behaviors we restricted our study to those members who completed all 3 TFEQ-R18
      questionnaires. These participants were defined as "completers" and the remaining
      as "noncompleters." The relationships between sex, change in eating behaviors,
      and total weight loss were studied using repeated measures ANOVA and Pearson
      correlation coefficient. RESULTS: In total, 22,800 individuals participated
      (females: 19,065/22,800, 83.62%; mean age 39.6, SD 11.4 years; BMI 29.0 kg/m(2);
      males: 3735/22,800, 16.38%; mean age 43.2, SD 11.7 years; BMI 30.8 kg/m(2)).
      Noncompleters (n=22,180) were younger and reported a lower score of uncontrolled
      eating and a higher score of cognitive restrained eating. Over time, completers
      (n=620) decreased their uncontrolled eating score (from 56.3 to 32.0; P<.001) and
      increased their cognitive restrained eating (from 50.6 to 62.9; P<.001). Males
      decreased their emotional eating (from 57.2 to 35.9; P<.001), but no significant
      change was found among females. The baseline cognitive restrained eating score
      was significantly and positively associated with weight loss for completers in
      both men (P=.02) and women (P=.002). CONCLUSIONS: To our knowledge, this is the
      largest TFEQ sample that has been documented. This Web-based weight loss
      intervention suggests that eating behaviors (cognitive restrained eating,
      uncontrolled eating, and emotional eating) measured by TFEQ-R18 were
      significantly changed during 6 months of participation. Our findings indicate
      differences in eating behaviors with respect to sex, but should be interpreted
      with caution because attrition was high.

PMID- 25367318
TI  - Lithium iodide as a promising electrolyte additive for lithium-sulfur batteries:
      mechanisms of performance enhancement.
AB  - Lithium Iodide (LiI) is reported as a promising electrolyte additive for lithium
      sulfur batteries. It induces formation of Li-ion-permeable protective coatings on
      both positive and negative electrodes, which prevent the dissolution of
      polysulfides on the cathode and reduction of polysulfides on the anode. In
      addition to enhancing the cell cycle stability, LiI addition also decreases the
      cell overpotential and voltage hysteresis. 

PMID- 25367317
TI  - Association of daily coffee and tea consumption and metabolic syndrome: results
      from the Polish arm of the HAPIEE study.
AB  - PURPOSE: The aim of this study was to evaluate whether daily consumption of
      coffee and tea was associated with components and prevalence of metabolic
      syndrome (MetS) in the Polish arm of the Health, Alcohol and Psychosocial factors
      In Eastern Europe cohort study. METHODS: A cross-sectional population-based
      survey including 8,821 adults (51.4% female) was conducted in Krakow, Poland.
      Coffee and tea consumption was evaluated using food frequency questionnaires.
      MetS was defined according to the International Diabetes Federation definition.
      Linear and logistic regression models were performed to estimate odds ratios and
      confidence intervals. RESULTS: Among high coffee and tea consumers (3 or more
      cups/day), high prevalence of female gender, young age, medium-high educational
      and occupational level, high total energy intake, and smoking habit were found.
      High coffee drinkers had lower BMI, waist circumference, systolic and diastolic
      blood pressure, triglycerides, and higher HDL cholesterol than those drinking
      less than 1 cup/day. In contrast, high tea consumers had lower BMI, waist
      circumference, but not diastolic blood pressure, which was higher than low
      drinkers. After adjusting for potential confounding factors, both higher coffee
      and tea consumption were negatively associated with MetS (OR 0.75, 95% CI 0.66,
      0.86 and OR 0.79, 95% CI 0.67, 0.92, respectively). Among specific components of
      MetS, high coffee consumption was negatively associated with waist circumference,
      hypertension, and triglycerides, whereas tea consumption with central obesity and
      fasting plasma glucose in women, but not in men. CONCLUSIONS: Coffee and tea
      consumption was negatively associated with MetS and some of its components.

PMID- 25367319
TI  - Prostate cancer. Foreword.
AB  - Professor Hiten Patel is an expert in Laparoscopic and Robotic Surgery for
      treating prostate disease. He is also a leading researcher in basic science and
      'clinical research. His basic science research is focused on studying the
      pathways for improving prostate cancer diagnosis and prognosis through biomarker
      application, and his clinical research includes new technology applications for
      training surgeons and improving patient care outcome. Prof Patel is also Chairman
      of the Urology group for the Enhanced Recovery after Surgery Society. 

PMID- 25367320
TI  - Biography: Dr Iain Frame, director of research, prostate cancer UK.
AB  - Sophia Maprayil, Commissioning Editor for Expert Review of Anticancer Therapy,
      talks to Dr Iain Frame, Director of Research for Prostate Cancer UK. Iain is
      Prostate Cancer UK's first Director of Research, responsible for overseeing the
      development and implementation of the charity's ambitious new research strategy.
      He joined Prostate Cancer UK in 2012 from Diabetes UK where he held the post of
      Research Director for 5 years. Since joining Prostate Cancer UK in 2012 Iain has
      overseen a dramatic increase in the charity's research spend, from 2 million a
      year, to 7.5 million a year. Previously Iain worked in research management at the
      Wellcome Trust and before that as a parasitologist and researcher exploring
      various aspects of molecular biology of a number of different parasites.

PMID- 25367321
TI  - Adjuvant versus salvage radiotherapy following radical prostatectomy: do the
      AUA/ASTRO guidelines have all the answers?
AB  - Debate continues surrounding the indications for adjuvant and salvage
      radiotherapy as the published randomized trials have only addressed adjuvant
      treatment. Salvage radiotherapy has been advocated to limit significant toxicity
      to patients that would not have benefited from immediate adjuvant radiotherapy.
      The American Urological Association and American Society for Radiation Oncology
      guideline released in 2013 has since recommended offering adjuvant therapy to all
      patients with any adverse features and salvage to those with prostate-specific
      antigen or local recurrence. The suggested criteria is limited in its application
      as it potentially subjects patients with few adverse features to adjuvant therapy
      despite not qualifying as high risk according to established postoperative
      predictive tools such as the Kattan nomogram. This article reviews the
      indications for postoperative radiotherapy, limitations of the guideline and
      alternative prognostication tools for clinicians faced with biochemical or
      locally recurrent post-prostatectomy prostate cancer. 

PMID- 25367322
TI  - Hypofractioned radiotherapy in prostate cancer: is it the next step?
AB  - There are many available options for prostate cancer treatment, including active
      surveillance, surgery, brachytherapy and external beam radiotherapy. Based on a
      radiobiological rationale, which considers the prostate tumor as a low alpha/beta
      tumor, the use of higher and fewer fractions to prostate cancer external beam
      radiotherapy treatment has been proposed. Instead of the traditional fractions of
      1.8-2.0 Gy per day, fractions higher than 2 Gy per day were the subject of a
      number of studies. In addition, new technologies such as intensity-modulated
      radiation therapy, image-guided radiation therapy, volumetric-modulated arch
      therapy and others have emerged as background for changing paradigms. Meanwhile,
      moderate and ultra-hypofractionation have been the subject of studies in recent
      years. Some moderate hypofractionation data from randomized controlled trials are
      ready to use, though other non-inferiority data are still lacking. The data on
      ultra-hypofractionation are still very new and require further evaluation to
      determine its long-term safety and efficacy. 

PMID- 25367323
TI  - Nutrition and prostate cancer: an overview.
AB  - There is increasing evidence for a link between nutrition, lifestyle and prostate
      cancer development. There is also growing interest from patients, with
      significant numbers of men using complementary and alternative medicines, such as
      vitamins and types of diet. Obesity and metabolic syndrome are important risk
      factors for prostate cancer and their management is key. The amount and type of
      fats consumed are also clearly related to prostate cancer risk. Saturated fats
      and trans fats are identified as having a negative impact. Nutraceuticals and
      supplements, particularly antioxidants, polyphenols and soy have evidence for
      benefit for prevention of prostate cancer and progression of the disease. A
      selection of nutrients is highlighted in this article. Nutritional therapists
      advise patients on how to incorporate these beneficial nutrients into their diet
      and guide them on supplement use. Further research is required to elucidate the
      connection between diet, nutrients and prostate cancer, including the field of
      nutrigenetics. 

PMID- 25367324
TI  - Focal cryotherapy of localized prostate cancer: a systematic review of the
      literature.
AB  - Radical/whole gland treatment for prostate cancer has significant side-effects.
      Therefore focal treatments such as cryotherapy have been used to treat localized
      lesions whilst aiming to provide adequate cancer control with minimal side
      effects. We performed a systematic review of Pubmed/Medline and Cochrane
      databases' to yield 9 papers for primary focal prostate cryotherapy and 2 papers
      for focal salvage treatment (radio-recurrent). The results of 1582 primary
      patients showed biochemical disease-free survival between 71-93% at 9-70 months
      follow-up. Incontinence rates were 0-3.6% and ED 0-42%. Recto-urethral fistula
      occurred in only 2 patients. Salvage focal cryotherapy had biochemical disease
      free survival of 50-68% at 3 years. ED occurred in 60-71%. Focal cryotherapy
      appears to be an effective treatment for primary localized prostate cancer and
      compares favorably to radical/whole gland treatments in medium-term oncological
      outcomes and side-effects. Although more studies are needed it is also effective
      for radio-recurrent cancer with a low complications rates. 

PMID- 25367325
TI  - Congenital and acquired ADAMTS13 deficiency: Two mechanisms, one patient.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening microangiopathy
      with a heterogeneous and largely unpredictable course. It is caused by ADAMTS13
      deficiency, that can be either congenital or due to anti-ADAMTS13 autoantibodies
      development. ADAMTS13 deficiency is necessary but not always sufficient to cause
      acute clinical manifestations and trigger factors may be needed. We report the
      case of a woman diagnosed with congenital TTP in her adulthood, presenting with
      anti-ADAMTS13 autoantibodies in acute phase during ticlopidine consumption.
      Noteworthy, the two ADAMTS13 mutations identified in this patient are novel: one
      is a splice-site mutation located in intron 11 (c.1308+2_5delTAGG) and the other
      is a point missense mutation in exon 29 (c.4184T>C leading to p.Leu1395Pro
      substitution). Since congenital TTP is an extremely rare disease and drug-induced
      TTP is an uncommon side effect of treatment with ticlopidine, the simultaneous
      occurrence of both mechanisms of disease in one patient is exceptional. This case
      represents TTP as a multifactorial disease, with ADAMTS13 genetic abnormality and
      environmental exposures acting together in determining individual clinical
      phenotype.

PMID- 25367326
TI  - Liver myofibroblasts from hepatitis B related liver failure patients may regulate
      natural killer cell function via PGE2.
AB  - BACKGROUND: Natural killer (NK) cells are abundant in the liver and constitute a
      major innate immune component that contributes to immune-mediated liver injury.
      However, few studies have investigated the phenotypes and functions of NK cells
      involved in hepatitis B related liver failure (LF), and the precise mechanism
      underlying NK cell regulation is not fully understood. METHODS: We detected the
      percentage and function of peripheral NK cells both in hepatitis B related LF
      patients and healthy volunteers by flow cytometry and isolated the liver
      myofibroblasts (LMFs) from hepatitis B related LF livers. To determine the
      possible effects of LMFs on NK cells, mixed cell cultures were established in
      vitro. RESULTS: We found a down-regulated percentage of peripheral NK cells in
      hepatitis B related LF patients, and their NK cells also displayed decreased
      activated natural cytotoxicity receptors (NCRs) and cytokine production. In a co
      culture model, LMFs sharply attenuated IL-2-induced NK cell triggering receptors,
      cytotoxicity, and cytokine production. The inhibitory effect of LMFs on NK cells
      correlated with their ability to produce prostaglandin (PG) E2. CONCLUSION: These
      data suggest that LMFs may protect against immune-mediated liver injury in
      hepatitis B related LF patients by inhibiting NK cell function via PGE2.

PMID- 25367327
TI  - Effects of Callistephus chinensis flower polyphones on improving metabolic
      disorders in high-fat diet-induced mice.
AB  - The aim of this study was to investigate the effects of Callistephus chinensis
      flower (CCF) polyphones on symptoms of metabolic syndrome in a newly developed
      high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) mouse model.
      C57BL/6J mice were fed a high fat diet (HFD; 50% energy as fat) with normal
      drinking fluid or HFD with CCF polyphones (50 mg L(-1) or 100 mg L(-1)) in
      drinking fluid for 12 weeks. As a comparison, mice fed a normal-fat (NFD; 10%
      energy as fat) and with normal drinking fluid were also included. The HFD group
      developed more severe symptoms of metabolic syndrome than the NFD group. CCF
      polyphones treatment significantly reduced fecal lipids compared to the HFD
      group, suggesting a strong indication of improved lipid metabolism. Liver damage
      and liver triglyceride levels were also decreased by CCF polyphones treatment.
      Moreover, both morphologic and histological detections indicated that CCF
      polyphones significantly reversed HFD-induced hepatic steatosis and liver injury.
      Furthermore, CCF polyphones significantly ameliorated both HFD-induced metabolic
      disorders, such as insulin resistance, and inflammatory cytokines, including
      interlukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Moreover,
      hepatic peroxisome proliferator-activated receptor (PPARalpha) and the gene
      involved in PPARalpha, Peroxisomal acyl-CoA oxidase (ACOX), were markedly up
      regulated at protein levels by CCF polyphones. Our results demonstrate that the
      HFD produces metabolic syndrome of NAFLD, and CCF polyphones treatment can
      alleviate these symptoms. The beneficial effects of CCF polyphones are associated
      with improved lipid metabolism and reduced levels of inflammatory cytokines. 

PMID- 25367328
TI  - Remote control of SMM behaviour via DTE ligands.
AB  - Chemists and physicists are continuously working to understand the mechanisms
      controlling molecular magnetism, especially single-molecule magnetism, to improve
      the magnetic properties, such as the blocking temperature. With the current
      research focused on preparing molecular devices, methods to control the
      components of the devices are necessary. Extensive research has shown that
      stimuli, such as light, electric current, etc., can be used to change the
      properties of the molecules making up the devices.
      Bis(carboxylato)dithienylethene (DTE) derivatives can be photo-isomerized between
      open and closed forms, i.e., unconjugated and pi-conjugated forms, and because of
      the carboxylate groups, it can be used to link 3d and/or 4f metal ions. Herein
      the use of DTE ligands to remotely control the magnetic properties of single
      molecule magnets is discussed. 

PMID- 25367329
TI  - Bacterial networks and co-occurrence relationships in the lettuce root
      microbiota.
AB  - Lettuce is one of the most common raw foods worldwide, but occasionally also
      involved in pathogen outbreaks. To understand the correlative structure of the
      bacterial community as a network, we studied root microbiota of eight ancient and
      modern Lactuca sativa cultivars and the wild ancestor Lactuca serriola by
      pyrosequencing of 16S rRNA gene amplicon libraries. The lettuce microbiota was
      dominated by Proteobacteria and Bacteriodetes, as well as abundant Chloroflexi
      and Actinobacteria. Cultivar specificity comprised 12.5% of the species.
      Diversity indices were not different between lettuce cultivar groups but higher
      than in L. serriola, suggesting that domestication lead to bacterial
      diversification in lettuce root system. Spearman correlations between operational
      taxonomic units (OTUs) showed that co-occurrence prevailed over co-exclusion, and
      complementary fluorescence in situ hybridization-confocal laser scanning
      microscopy (FISH-CLSM) analyses revealed that this pattern results from both
      potential interactions and habitat sharing. Predominant taxa, such as
      Pseudomonas, Flavobacterium and Sphingomonadaceae rather suggested interactions,
      even though these are not necessarily part of significant modules in the co
      occurrence networks. Without any need for complex interactions, single organisms
      are able to invade into this microbial network and to colonize lettuce plants, a
      fact that can influence the susceptibility to pathogens. The approach to combine
      co-occurrence analysis and FISH-CLSM allows reliably reconstructing and
      interpreting microbial interaction networks. 

PMID- 25367330
TI  - Distance decay and persistent health care disparities in South Africa.
AB  - BACKGROUND: Access to health care is a particular concern given the important
      role of poor access in perpetuating poverty and inequality. South Africa's
      apartheid history leaves large racial disparities in access despite post
      apartheid health policy to increase the number of health facilities, even in
      remote rural areas. However, even when health services are provided free of
      charge, monetary and time costs of travel to a local clinic may pose a
      significant barrier for vulnerable segments of the population, leading to overall
      poorer health. METHODS: Using newly available health care utilization data from
      the first nationally representative panel survey in South Africa, together with
      administrative geographic data from the Department of Health, we use graphical
      and multivariate regression analysis to investigate the role of distance to the
      nearest facility on the likelihood of having a health consultation or an attended
      birth. RESULTS: Ninety percent of South Africans live within 7 km of the nearest
      public clinic, and two-thirds live less than 2 km away. However, 14% of Black
      African adults live more than 5 km from the nearest facility, compared to only 4%
      of Whites, and they are 16 percentage points less likely to report a recent
      health consultation (p < 0.01) and 47 percentage points less likely to use
      private facilities (p < 0.01). Respondents in the poorest income quintiles live
      0.5 to 0.75 km further from the nearest health facility (p < 0.01). Racial
      differentials in the likelihood of having a health consultation or an attended
      birth persist even after controlling for confounders. CONCLUSIONS: Our results
      have two policy implications: minimizing the distance that poor South Africans
      must travel to obtain health care and improving the quality of care provided in
      poorer areas will reduce inequality. Much has been done to redress disparities in
      South Africa since the end of apartheid but progress is still needed to achieve
      equity in health care access.

PMID- 25367331
TI  - Production of nitrogen oxide gases from an oxic/anoxic process via nitrite:
      influence of liquid parameters and impact on mass balance.
AB  - The produced nitrogen oxides from the biological treatment of swine and dairy
      anaerobic supernatant are evaluated. The quantification of the emissions has been
      conducted in a continuous way and coupled with batch tests to determine the
      mechanisms of formation. Using a continuous monitoring system, N2O and NO forms
      are present in higher quantities than NO2. The elevated emissions are linked with
      the increment of the influent nitrogen load both in the daily variations and in
      the long period. The NH4-N and NO2-N accumulations are recognized as the main
      parameters which determine the great nitrogen oxide emissions even at dissolved
      oxygen concentration of around 2 mgL(-1). The nitrogen oxides' impacts are
      between 0.0034 and 0.0044N% for the N2O and between 0.0020 and 0.0026N% for NO. A
      strict dependence between the N2O and the oxidation reduction potential is found.

PMID- 25367332
TI  - The electrodeposition of FeCrNi stainless steel: microstructural changes induced
      by anode reactions.
AB  - The FeCrNi alloy, whose composition is close to that of stainless steel 304, was
      prepared by electrodeposition and characterized. Nanocrystalline FeCrNi (nc
      FeCrNi) was obtained by employing a double-compartment cell where the anode is
      separated from the cathode compartment, while amorphous FeCrNi (a-FeCrNi) was
      deposited in a conventional single electrochemical cell. The carbon content of nc
      FeCrNi was found to be significantly lower than that of a-FeCrNi, suggesting that
      carbon inclusion is responsible for the change in the microstructure. The major
      source of carbon is associated with the reaction compounds at the anode
      electrode, presumably decomposed glycine. Crystal structure analysis by XRD and
      TEM revealed that the as-deposited nc-FeCrNi deposits consist of alpha-Fe which
      transforms to gamma-Fe upon thermal annealing. Nanoindentation tests showed that
      nc-FeCrNi exhibits higher hardness than a-FeCrNi, which is consistent with the
      inverse Hall-Petch behavior. 

PMID- 25367333
TI  - Epstein-Barr virus at 50-future perspectives.
AB  - The special November and December issues of the Chinese Journal of Cancer
      celebrate the 50th anniversary of the discovery of Epstein-Barr virus (EBV) with
      a series of reviews covering the association of the virus with various cancers,
      with special emphasis on the role of EBV in the pathogenesis of nasopharyngeal
      cancer (NPC). The restricted geographic prevalence of NPC along with the tumor's
      consistent association with EBV infection has fascinated scientists and
      clinicians ever since it was first suggested in 1966. As in all cancers, NPC
      development reflects the complex interplay between host genes and environmental
      factors, but the essential role of EBV infection provides important insight into
      the etiology of this tumor. Indeed, it is this understanding that is now
      translating into exciting diagnostic and therapeutic opportunities. 

PMID- 25367334
TI  - MicroRNAs in nasopharyngeal carcinoma.
AB  - MicroRNAs (miRNAs) provide insight into both the biology and clinical behavior of
      many human cancers, including nasopharyngeal carcinoma (NPC). The dysregulation
      of miRNAs in NPC results in a variety of tumor-promoting effects. Furthermore,
      several miRNAs are prognostic markers for NPC. In addition to cellular miRNAs,
      NPC samples also often contain miRNAs encoded by Epstein-Barr virus, and these
      miRNAs may impact NPC biology by targeting both cellular and viral genes. Given
      their numerous putative roles in NPC development and progression, a thorough
      understanding of the impact of miRNA dysregulation in NPC is expected to shed
      light on useful biomarkers and therapeutic targets for the clinical management of
      this disease. In this review, we describe the efforts to date to identify and
      characterize such miRNAs in the context of NPC. 

PMID- 25367336
TI  - Perioperative Mortality and Long-Term Survival in 80 Dogs and 32 Cats Undergoing
      Excision of Thymic Epithelial Tumors.
AB  - OBJECTIVE: To examine perioperative mortality, long-term survival, causes of
      death, and prognostic factors for dogs and cats undergoing surgical excision of
      thymic epithelial tumors (TETs). STUDY DESIGN: Multi-institutional case series.
      ANIMALS: Eighty dogs and 32 cats. METHODS: Follow-up information was obtained for
      dogs and cats that underwent surgical excision of a TET between 2001 and 2012.
      RESULTS: Perioperative mortality was 20% in dogs and 22% in cats. No independent
      risk factors for perioperative mortality were identified. The estimated median
      survival time for all dogs was 1.69 years (95% CI 0.56-4.32) and the 1- and 4
      year survival rates were 55% (95% CI 44-67) and 44% (95% CI 32-56). The estimated
      median survival time for all cats was 3.71 years (95% CI 0.56-unestimatable) and
      the 1- and 4-year survival rates were 70% (95% CI 53-87) and 47% (95% CI 0-100).
      Of animals that survived to discharge, 42% of dogs and 20% of cats eventually
      died of TET-related causes. The presence of paraneoplastic syndromes (hazard
      ratio [HR] 5.78, 95% CI 1.64-20.45, P = .007) or incomplete histologic margins
      (HR 6.09, 95% CI 1.50-24.72, P = .01) were independently associated with
      decreased survival in dogs. No significant predictors of survival were identified
      in cats. Conclusions regarding the effect of chemotherapy or radiation therapy
      could not be made. CONCLUSIONS: While there is substantial risk of perioperative
      death in dogs and cats undergoing surgery for TETs, many animals that survive to
      discharge have prolonged survival. Survival is significantly decreased in dogs
      with paraneoplastic syndromes or incomplete histologic margins.

PMID- 25367335
TI  - The interplay of host genetic factors and Epstein-Barr virus in the development
      of nasopharyngeal carcinoma.
AB  - The interplay between host cell genetics and Epstein-Barr virus (EBV) infection
      contributes to the development of nasopharyngeal carcinoma (NPC). Understanding
      the host genetic and epigenetic alterations and the influence of EBV on cell
      signaling and host gene regulation will aid in understanding the molecular
      pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and
      therapy. In this review, we provide an update of the oncogenes and tumor
      suppressor genes associated with NPC, as well as genes associated with NPC risk
      including those involved in carcinogen detoxification and DNA repair. We also
      describe the importance of host genetics that govern the human leukocyte antigen
      (HLA) complex and immune responses, and we describe the impact of EBV infection
      on host cell signaling changes and epigenetic regulation of gene expression. High
      power genomic sequencing approaches are needed to elucidate the genetic basis for
      inherited susceptibility to NPC and to identify the genes and pathways driving
      its molecular pathogenesis. 

PMID- 25367337
TI  - Knockdown of anterior gradient 2 expression extenuates tumor-associated
      phenotypes of SNU-478 ampulla of Vater cancer cells.
AB  - BACKGROUND: Anterior gradient 2 (AGR2) has been implicated in tumor-associated
      phenotypes such as cell viability, invasion and metastasis in various human
      cancers. However, the tumor promoting activity of AGR2 has not yet been
      determined in biliary tract cancers. Thus, we examined the expression of AGR2 and
      its tumor-promoting activity in biliary tract cancer cells in this study.
      METHODS: Expression of AGR2 mRNA and protein was analyzed by real time RT-PCR and
      western blotting, respectively. MTT assay was employed to measure cell viability
      and pulsed BrdU incorporation by proliferating cells was monitored by flow
      cytometry. Soft agar colony formation assay and transwell invasion assay were
      employed to determine anchorage-independent growth and in vitro invasion of the
      tumor cells, respectively. In vivo tumor formation was examined by injection of
      tumor cells into immunocompromised mice subcutaneously. Statistical analysis was
      performed with 2-tailed unpaired Student's t-test for continuous data and with
      one-way ANOVA for multiple group comparisons. Bonferroni tests were used for post
      hoc 2-sample comparisons. RESULTS: AGR2 mRNA was detected in SNU-245, SNU-478,
      and SNU-1196 cell lines, and its protein expression was confirmed in SNU-478 and
      SNU-245 cell lines by western blot analysis. Knockdown of AGR2 expression with an
      AGR2-specific short hairpin RNA (shRNA) in SNU-478, an ampulla of Vater cancer
      cell line resulted in decreased cell viability and in decreased anchorage
      independent growth by 98%. The AGR2 knockdown also increased the sensitivity of
      the cells to chemotherapeutic drugs, including gemcitabine, 5-fluorouracil and
      cisplatin. In addition, SNU-478 cells expressing AGR2-shRNA failed to form
      detectable tumor xenografts in nude mice, whereas control cells formed tumors
      with an average size of 179 +/- 84 mm3 in 3 weeks. Overexpression of AGR2 in SNU
      869 cells significantly increased cell viability through enhanced cell
      proliferation and the number of MatrigelTM-invading cells compared with AGR2
      negative SNU-869 cells. CONCLUSIONS: Our findings implicate that AGR2 expression
      augments tumor-associated phenotypes by increasing proliferative and invasive
      capacities of the ampulla of Vater cancer cells.

PMID- 25367338
TI  - Cohnella capsici sp. nov., a novel nitrogen-fixing species isolated from Capsicum
      annuum rhizosphere soil, and emended description of Cohnella plantaginis.
AB  - A novel bacterial strain designated YN-59(T) was isolated from Capsicum annuum
      rhizosphere soil in China. The isolate was found to be aerobic, Gram-positive,
      rod-shaped and to form ellipsoidal or oval spores positioned centrally in swollen
      sporangia. On the basis of 16S rRNA gene sequence analysis, the isolated strain
      YN-59 was determined to be related to members of genus Cohnella. High levels of
      16S rRNA gene sequence similarity were found between strain YN-59 and Cohnella
      plantaginis DSM 25424(T) (98.5 %) and Cohnella ginsengisoli DSM18997(T) (97.3 %);
      the 16S rRNA gene sequence similarities between strain YN-59 and the other
      strains recognized members of the genus Cohnella were below 97 %. The DNA-DNA
      hybridization values of strain YN-59 with C. plantaginis DSM 25424(T) and C.
      ginsengisoli DSM18997(T) were 44.2 +/- 8.4 and 28.8 +/- 5.8 %, respectively. The
      DNA G + C content of strain YN-59(T) was determined to be 59.32 mol %. The major
      isoprenoid quinone was identified as MK-7 and the predominant fatty acids as
      anteiso-C15:0 (45.32 %), iso-C16:0 (19.19 %), iso-C15:0 (9.65 %) and C16:0 (8.91
      %). The polar lipids of strain YN-59(T) were found to consist of
      diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol;
      several unidentified phospholipids were also detected. The diagnostic diamino
      acid in the cell wall was identified as meso-diaminopimelic. On the basis of its
      phenotypic and genotypic characteristics and levels of DNA-DNA hybridization,
      strain YN-59(T) is considered to represent a novel species of the genus Cohnella,
      for which the name Cohnella capsici sp. nov. (type strain YN-59(T) = CGMCC
      1.12046(T) = JCM 19168(T)) is proposed. 

PMID- 25367339
TI  - Two yeast species Cystobasidium psychroaquaticum f.a. sp. nov. and Cystobasidium
      rietchieii f.a. sp. nov. isolated from natural environments, and the transfer of
      Rhodotorula minuta clade members to the genus Cystobasidium.
AB  - Many species of dimorphic basidiomycetes are known only in their asexual phase
      and typically those pigmented in different hues of red have been classified in
      the large polyphyletic genus Rhodotorula. These yeasts are ubiquitous and include
      a few species of some clinical relevance. The phylogenetic distribution of
      Rhodotorula spans three classes: Microbotryomycetes, Cystobasidiomycetes and
      Exobasidiomycetes. Here, the presented multi-gene analyses resolved phylogenetic
      relationships between the second largest group of Rhodotorula and the
      mycoparasite Cystobasidium fimetarium (Cystobasidiales, Cystobasidiomycetes,
      Pucciniomycotina). Based on the results, we propose the transfer of nine species
      belonging to the Rhodotorula minuta clade into the genus Cystobasidium. As a
      result, the clinically relevant species R. minuta will be renamed Cystobasidium
      minutum. This proposal follows ongoing reassessments of the anamorphic genus
      Rhodotorula reducing the polyphyly of this genus. The delimitation of the R.
      minuta clade from Rhodotorula species comprised in Sporidiobolales including the
      type species Rhodotorula glutinis is an important step to overcome obsolete
      generic placements of asexual basidiomycetous yeasts. Our proposal will also help
      to distinguish most common red yeasts from clinical samples such as members of
      Sporidiobolales and Cystobasidiales. The diagnosis of the genus Cystobasidium is
      amended by including additional characteristics known for the related group of
      species. The taxonomic change enables us to classify two novel species with the
      phylogenetically related members of the R. minuta clade in Cystobasidium. The
      recently from natural environments isolated species are described here as
      Cystobasidium psychroaquaticum f.a. sp. nov. (K-833(T) = KBP 3881(T) = VKPM Y
      3653(T) = CBS 11769(T) = MUCL 52875(T) = DSM 27713(T)) and Cystobasidium
      rietchiei f.a. sp. nov. (K-780(T) = KBP 4220(T) = VKPM Y-3658(T) = CBS 12324(T) =
      MUCL 53589(T) = DSM 27155(T)). The new species were registered in MycoBank under
      MB 809336 and MB 809337, respectively. 

PMID- 25367340
TI  - VeA of Aspergillus niger increases spore dispersing capacity by impacting
      conidiophore architecture.
AB  - Aspergillus species are highly abundant fungi worldwide. Their conidia are among
      the most dominant fungal spores in the air. Conidia are formed in chains on the
      vesicle of the asexual reproductive structure called the conidiophore. Here, it
      is shown that the velvet protein VeA of Aspergillus niger maximizes the diameter
      of the vesicle and the spore chain length. The length and width of the
      conidiophore stalk and vesicle were reduced nearly twofold in a DeltaveA strain.
      The latter implies a fourfold reduced surface area to develop chains of spores.
      Over and above this, the conidial chain length was approximately fivefold
      reduced. The calculated 20-fold reduction in formation of conidia by DeltaveA
      fits the 8- to 17-fold decrease in counted spore numbers. Notably, morphology of
      the DeltaveA conidiophores of A. niger was very similar to that of wild-type
      Aspergillus sydowii. This suggests that VeA is key in conidiophore architecture
      diversity in the fungal kingdom. The finding that biomass formation of the A.
      niger DeltaveA strain was reduced twofold shows that VeA not only impacts
      dispersion capacity but also colonization capacity of A. niger. 

PMID- 25367341
TI  - Halorubrum laminariae sp. nov., isolated from the brine of salted brown alga
      Laminaria.
AB  - Two halophilic archaeal strains, R60(T) and R61, were isolated from the brine of
      salted brown alga Laminaria. Cells of the two strains were observed to be rod
      shaped, stain Gram-negative and to lyse in distilled water. Strain R60(T) was
      found to contain gas vacuoles and to produce pink-pigmented colonies, while
      strain R61 lacked gas vacuoles and produces red-pigmented colonies. Both strains
      were found to be able to grow at 20-50  degrees C (optimum 30  degrees C), at 1.7
      4.8 M NaCl (optimum 2.6-3.1 M NaCl), at 0-1.0 M MgCl2 (optimum 0.005-0.1 M MgCl2)
      and at pH 6.0-9.5 (optimum pH 7.0). The major polar lipids were identified as
      phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester,
      phosphatidylglycerol sulfate and one major glycolipid chromatographically
      identical to a sulfated mannosyl glucosyl diether produced by Halorubrum members
      of the Halobacteriaceae. The 16S rRNA gene sequences of the two strains were 99.9
      % identical, showing 94.6-98.0 % similarity to those of members of the genus
      Halorubrum. The EF-2 gene similarity between strains R60(T) and R60 was 100 % and
      showed 84.6-94.5 % similarity to those of members of the genus Halorubrum. The
      DNA G+C contents of the two strains were determined to be 63.0 mol %. The DNA-DNA
      hybridization value between strain R60(T) and strain R61 was 92 % and the two
      strains showed low DNA-DNA relatedness with the most related members of
      Halorubrum. The phenotypic, chemotaxonomic and phylogenetic properties suggest
      that strain R60(T) (= CGMCC 1.12689(T) = JCM 30040(T)) and strain R61 (= CGMCC
      1.12696) represent a novel species of the genus Halorubrum, for which the name
      Halorubrum laminariae sp. nov. is proposed. 

PMID- 25367342
TI  - Usnic acid, a lichen secondary metabolite inhibits Group A Streptococcus
      biofilms.
AB  - Group A Streptococci (GAS) are involved in a number of life threatening diseases
      and biofilm formation by these pathogens are considered as an important virulence
      determinant as it mediates antibiotic resistance among them. In the present
      study, we have explored the ability of (+)-usnic acid, a lichen secondary
      metabolite, as an antibiofilm agent against four serotypes of Streptococcus
      pyogenes causing pharyngitis. Usnic acid inhibited the biofilms of M serotypes
      M56, st38, M89 efficiently and the biofilm of M74 to a lesser extent. Confocal
      imaging of the treated samples showed that usnic acid reduced the biomass of the
      biofilms when compared to that of the control. Fourier Transfer Infrared (FT-IR)
      spectroscopy indicated that usnic acid reduced the cellular components (proteins
      and fatty acids) of the biofilms. Interestingly, the FT-IR spectrum further
      revealed that usnic acid probably acted upon the fatty acids of the biofilms as
      evident from the disappearance of a peak at 2,455-2,100 cm(-1) when compared to
      the control only in serotypes M56, st38 and M89 but not in M74. The present study
      shows, for the first time, that usnic acid can act as an effective antibiofilm
      agent against GAS. 

PMID- 25367344
TI  - Nonthymoma-associated exfoliative dermatitis in 18 cats.
AB  - BACKGROUND: Exfoliative dermatitis has been described in cats as a paraneoplastic
      skin disease associated with thymoma. There are anecdotal reports of cases
      without thymoma, with various suspected aetiologies. HYPOTHESIS/OBJECTIVES: To
      identify common features, underlying causes, response to therapy and outcome of
      nonthymoma-associated exfoliative dermatitis in cats. METHODS: Retrospective
      analysis was carried out of cases presented to dermatology referral centres or
      cases submitted for histopathological examination. Detailed historical and
      clinical data were obtained and evaluated statistically. Histopathology was
      reviewed in a blinded fashion by three dermatopathologists, and PCR for
      herpesvirus was performed. RESULTS: Eighteen cats fulfilled all inclusion
      criteria. There was no sex, age or breed predisposition. All cats presented with
      severe generalized (77%) or multifocal exfoliation (23%); 12 cats were severely
      depressed. In all cats, thymoma was excluded radiographically and feline
      leukaemia virus tests were negative. Additional imaging procedures in 14 cats and
      postmortem examination in two cats did not detect neoplasia. Histopathology
      revealed interface dermatitis, mural interface folliculitis and sebaceous
      adenitis indistinguishable from findings in thymoma-associated cases. PCR for
      herpes DNA was negative. No aetiology was identified. Treatment in 12 cases
      consisted of immunosuppressive doses of corticosteroids and/or ciclosporin; one
      responded to antibiotics, one to shampoo, two went into spontaneous remission,
      and two did not receive any therapy and were euthanized. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Nonthymoma-associated exfoliative dermatitis in cats is clinically
      and histopathologically indistinguishable from thymoma-associated cases. Most
      cases benefit from immunosuppressive therapy; therefore, an immunopathological
      response to an undefined trigger is suspected.

PMID- 25367345
TI  - Cyclophosphamide treatment for idiopathic inflammatory myopathies and related
      interstitial lung disease: a systematic review.
AB  - The purpose of this study is to review and summarize published information on the
      use, effectiveness, and adverse effects of cyclophosphamide (CYC) in the
      management of idiopathic inflammatory myopathies (IIM) and IIM-related
      interstitial lung disease (IIM-ILD). We performed a systematic search on various
      databases from May 1975 to May 2014 to find articles concerning CYC therapy in
      IIM and IIM-ILD. The initial search involved 310 articles, and the 12 articles
      that met the study criteria were analyzed in detail. All studies were non
      randomized. Intravenous CYC (IVCYC) was administered as treatment for IIM in 11
      of the studies. Additionally, eight of the twelve studies assessed the effect of
      CYC in developing resistance steroids or in refractory IIM. IVCYC pulses of 0.3
      1.0 g/m(2) or 10-30 mg/kg were applied at weekly to monthly intervals for 6-12
      months together with either glucocorticoids or another immunosuppressive agent.
      According to a comprehensive analysis of the studies, 80.8 % (42/52) and 73.1 %
      (38/52) of patients showed improvement in muscle strength and function. The CK
      levels of 87.5 % (35/40) of patients fell. The forced vital capacity (FVC) and
      diffusing capacity for carbon monoxide (DLCO) improved in 57.6 % (34/59) and 64.3
      % (27/42) of patients. The high-resolution computed tomography (HRCT) findings
      improved in 67.3 % (35/52) of patients. IVCYC treatment allowed 58.1 % (25/43) of
      acute/subacute IIM-ILD patients to survive. However, 18 patients died, and the
      histopathological findings revealed that the 12 deaths were due to diffuse
      alveolar damage (DAD). HRCT revealed a ground glass (GrG) pattern in 66.7 %
      (12/18) of the deaths. Of the patients who died, 70 % (7/10) had
      pneumomediastinum. IVCYC seems to improve both muscle strength and function and
      lung function in refractory IIM and IIM-ILD patients, and it appears to be
      relatively well tolerated and safe. 

PMID- 25367346
TI  - Vitamin D status in children with systemic lupus erythematosus and its
      association with clinical and laboratory parameters.
AB  - To assess serum 25-hydroxyvitamin D (25-OH vitamin D) status in Saudi children
      with systemic lupus erythematosus (SLE) and determined its association with
      clinical, laboratory variables and disease activity. This cross-sectional study
      comprised children with SLE who are followed at Pediatric Lupus Clinic. All
      patients reviewed for demographic data, age of first disease manifestations, and
      disease duration. All included patients evaluated for disease activity, which is
      completed by using the SLE Disease Activity Index (SLEDAI) and laboratory
      parameters included a vitamin D profile, bone markers at enrollment and 3 months
      later. All patients treated with Cholecalciferol (vitamin D3 2000 IU daily) and
      calcium supplement (Caltrate 600 mg twice daily). Twenty-eight patients (26
      female) with mean age of 9.7 years completed the evaluation. Fifteen patients had
      more than one major organ involvement. Most of the patients are on daily vitamin
      D3 supplement (800 IU) prior enrollment. The baseline assessment revealed 24
      patients had low levels of serum 25-OH vitamin D levels, with a mean of 51.1 +/-
      33.6 nmol/L; 25 patients had high autoantibodies; and 18 patients had high
      protein/creatinine ratio, with a mean of 0.9 +/- 1.7. Bone density was subnormal
      with a mean of 0.9 +/- 1. The mean disease activity was 6 +/- 5.6. Levels of 25
      OH vitamin D correlated inversely with autoantibodies and SLEDAI and positively
      with bone density but not statistically significant. After 3 months, treatment of
      vitamin D3 (2000 IU daily) and Caltrate (600 mg twice daily), 17 patients had
      improvement in SLEDAI score and autoimmune markers. Disease activity of childhood
      SLE is probably linked with low serum 25-OH vitamin D levels. Accordingly, high
      daily vitamin D3 supplement could potentially impact disease activity of
      childhood SLE. Further follow up and more patients needed to confirm this
      finding. 

PMID- 25367347
TI  - Experience with alendronate treatment for 7 years among Japanese men with
      osteoporosis or osteopenia and clinical risk factors for fractures.
AB  - A retrospective study was performed to evaluate the outcome of alendronate
      treatment for 7 years among Japanese men with osteoporosis or osteopenia and
      clinical risk factors for fractures. Thirty-five Japanese men with osteoporosis
      or osteopenia and clinical risk factors for fractures (mean age at baseline 58.2
      years) who had been treated with alendronate for over 7 years in our outpatient
      clinic were analyzed. The lumbar spine or total hip bone mineral density (BMD)
      was measured using dual energy X-ray absorptiometry; the urinary levels of cross
      linked N-terminal telopeptides of type I collagen (NTX) and the serum levels of
      alkaline phosphatase (ALP) were monitored; the incidence of fractures during the
      7-year treatment period was then assessed. The urinary NTX and serum ALP levels
      decreased (-46.1% at 3 months and -21.1% at 7 years, respectively) and the lumbar
      spine and total hip BMD increased (+14.2 and +10.1% at 7 years, respectively),
      compared with the baseline values. Four patients (11.4%) experienced vertebral
      fractures, and one patient (2.9%) experienced a nonvertebral fracture. No serious
      adverse events were observed, including osteonecrosis of the jaw or atypical
      femoral fractures. These results suggested that alendronate suppressed bone
      turnover and increased the lumbar spine and total hip BMD from the baseline
      values over the course of the 7-year treatment period without causing any severe
      adverse events in Japanese men with osteoporosis or osteopenia and clinical risk
      factors for fractures.

PMID- 25367348
TI  - Wolf-living with SLE in a novel.
AB  - Living with SLE is a major task for the patients and their social environment. In
      modern health care, quality of life is increasingly incorporated as an important
      outcome. Studying novels about illness is a new method of exploring quality of
      life in patients with an illness. In this paper, we use the novel A tribe of
      women by Herve Bazin as data to explore how a patient with SLE gives meaning to
      her illness and how her social environment reacts toward the illness and its
      treatment. We find that the novel-probably the only one where SLE is a major
      subject-offers a rich set of data on "living with SLE". Our findings may be
      instrumental in encouraging health care providers to explore quality of life in
      patients with SLE, incorporating self-management in order to improve their
      quality of life, and in teaching medical students about "medical humanities".

PMID- 25367349
TI  - Sleep-related symptoms and sleep-disordered breathing in adult Pompe disease.
AB  - BACKGROUND AND PURPOSE: Respiratory muscle weakness is the major cause of early
      death in patients with adult Pompe disease. It first manifests as nocturnal
      hypercapnia, eventually leading to sleep disruption. Sleep-related symptoms along
      with motor performance, forced vital capacity (FVC) and respiratory symptoms were
      investigated in 65 adult patients with Pompe disease. METHODS: Patients answered
      the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale, the
      Fatigue Severity Scale, the Rotterdam Nine-item Handicap Scale, the SF-36 health
      related quality of life questionnaire, and a respiratory symptom questionnaire.
      In all patients, the 6-min walk test was performed and FVC was obtained.
      Polysomnography and oxycapnometry results were available in 31 patients. RESULTS:
      Sixty patients received enzyme replacement therapy, and 32 individuals were on
      home ventilatory support. Reduced sleep quality was highly prevalent (PSQI > 5;
      43.1%) and correlated with both excessive daytime sleepiness (Epworth Sleepiness
      Scale > 10; 24.6%) and fatigue (Fatigue Severity Scale > 4; 72.3%). The SF-36
      health-related quality of life questionnaire was reduced in the physical domains,
      and was inversely correlated with sleep quality, FVC and motor performance. In 11
      out of 17 non-ventilated patients with polysomnography records, sleep-disordered
      breathing was present, and duration of nocturnal oxygen desaturation (SaO2 < 90%)
      was significantly correlated to the PSQI global score. CONCLUSIONS: In adult
      Pompe disease, sleep disturbances are a common cause of excessive daytime
      sleepiness and fatigue. Sleep-related symptoms may be indicative of respiratory
      muscle weakness and should give rise to further work-up of sleep-disordered
      breathing.

PMID- 25367350
TI  - Nikolay Ivanovich Pirogov: a surgeon's contribution to military and civilian
      anaesthesia.
AB  - A key figure in the development of anaesthesia in Russia was the surgeon Nikolay
      Ivanovich Pirogov (1810-1881). He experimented with ether and chloroform and
      organised the general introduction of anaesthesia in Russia for patients
      undergoing surgery. He was the first to perform systematic research into
      anaesthesia-related morbidity and mortality. More specifically, he was one of the
      first to administer ether anaesthesia on the battlefield, where the principles of
      military medicine that he established remained virtually unchanged until the
      outbreak of the Second World War. 

PMID- 25367351
TI  - Two New Steroidal Saponins from Ypsilandra thibetica.
AB  - Two new monosaccharide steroidal saponins, named ypsilandroside S (1) and
      ypsilandroside T (2), have been isolated from the whole plants of Ypsilandra
      thibetica. Their structures were elucidated as heloniogenin 3-O-beta-D
      apiofuranoside (1) and pregna 5,16-dien-3beta,12alpha-diol-20-one-3-O-beta-D
      apiofuranoside (2) by spectroscopic techniques (1D and 2D NMR, MS). Compounds 1
      and 2 were tested for their inhibitory effects on lipopolysaccharide-induced
      nitric oxide production in RAW 264.7 cells. 

PMID- 25367353
TI  - Retraction note to: Magnesium and iron contents of leukemic lymphocytes in acute
      leukemias and hemolytic anemia.

PMID- 25367352
TI  - Impacts of feeding selenium-methionine and chromium-methionine on performance,
      serum components, antioxidant status, and physiological responses to
      transportation stress of Baluchi ewe lambs.
AB  - The effects of selenium-methionine (Se-Met) and chromium-methionine (Cr-Met)
      supplementation on performance and response to transportation stress were studied
      on 24 Baluchi ewe lambs (18-20 weeks of age) for 9 weeks. The lambs were randomly
      assigned to four dietary treatments: (1) control; (2) 1.5 mg supplemental Se
      Met/kg dry matter (DM) of diet; (3) 0.8 mg supplemental Cr-Met/kg DM of diet; and
      (4) 1.5 mg Se-Met plus 0.8 mg Cr-Met/kg DM of diet (Se-Cr-Met). At the
      commencement of week 8, a road transportation stress (TS) was carried out for 30
      min. Lambs fed Cr-Met and Se-Cr-Met diets had higher feed intake than the control
      and Se-Met animals (P < 0.0001). Lambs on Cr-Met diet showed higher average daily
      gain (ADG) compared to the control group (P = 0.007). Se-Met and Cr-Met
      supplementation alone or in combination significantly (P < 0.05) reduced feed
      conversion ratio (FCR). The animals that received Se-Met (P = 0.014), Cr-Met (P =
      0.005), and Se-Cr-Met (P = 0.003) supplemented diets had lower glucose
      concentration than the control. Lambs on Cr-Met had higher blood T3 concentration
      than control animals (P = 0.040), while Cr-Met (P = 0.039) and Se-Cr-Met (P =
      0.032) supplementation increased triiodothyronine (T3) to thyroxin (T4) ratio.
      Animals fed Se-Met and/or Cr-Met supplements had lower blood malondialdehyde
      (MDA) in week 9 of the experiment (P < 0.05). Blood ferric-reducing antioxidant
      power (FRAP) tended to be higher in the Se-Met- and Se-Cr-Met-supplemented groups
      (P < 0.1).TS reduced feed intake in lambs fed the control diet in week 8 of the
      experiment (P = 0.003). The lambs given with supplemental Cr-Met exhibited lower
      glucose concentration before transportation (BT) (P = 0.029) and after
      transportation (AT) (P = 0.016) compared to the control. Lambs fed Se-Cr-Met had
      the lowest cortisol concentration BT (P < 0.05). It was concluded that feeding Se
      Met and/or Cr-Met supplements could improve growth performance and be beneficial
      in attenuating the adverse effects of transportation stress in Baluchi ewe lambs.

PMID- 25367354
TI  - Cryogun cryotherapy for oral leukoplakia and adjacent melanosis lesions.
AB  - BACKGROUND: Our previous study has shown that cryogun cryotherapy is a good and
      effective treatment modality for oral leukoplakia. METHODS: In this study, we
      used cryogun cryotherapy to treat 72 oral leukoplakia and adjacent smoking
      induced melanosis (OLM) lesions on the buccal mucosae. RESULTS: Of 72 OLM
      lesions, 14 had epithelial hyperplasia with parakeratosis, 24 had epithelial
      hyperplasia with hyperkeratosis, 26 had mild dysplasia, seven had moderate
      dysplasia, and one had severe dysplasia. Complete regression was achieved in all
      72 OLM lesions after a mean of 3.3 +/- 1.3 cryogun cryotherapy treatments. We
      found that OLM lesions in patients without smoking habit, with the greatest
      diameter < 2.8 cm, with epithelial dysplasia, or with a surface keratin thickness
      <= 50 MUm needed significantly fewer mean number of cryogun cryotherapy treatment
      to achieve complete regression than those OLM lesions in patients with smoking
      habit, with the greatest diameter >= 2.8 cm, without epithelial dysplasia, or
      with a surface keratin thickness > 50 MUm (all P-values < 0.001), respectively.
      Univariate logistic regression analyses showed that the greatest diameter,
      epithelial dysplasia, smoking habit, and surface keratin thickness were the
      factors influencing the cryogun cryotherapy treatment number (all P-values <
      0.001). However, only the greatest diameter < 2.8 cm (P < 0.001) was an
      independent factor influencing the number of cryogun cryotherapy treatment
      required to achieve complete regression of the OLM lesion by multivariate
      logistic regression analyses. CONCLUSION: Cryogun cryotherapy is an effective
      treatment modality for OLM lesions.

PMID- 25367355
TI  - Radiation doses for pediatric nuclear medicine studies: comparing the North
      American consensus guidelines and the pediatric dosage card of the European
      Association of Nuclear Medicine.
AB  - BACKGROUND: Estimated radiation dose is important for assessing and communicating
      the risks and benefits of pediatric nuclear medicine studies. Radiation dose
      depends on the radiopharmaceutical, the administered activity, and patient
      factors such as age and size. Most radiation dose estimates for pediatric nuclear
      medicine have not been based on administered activities of radiopharmaceuticals
      recommended by established practice guidelines. The dosage card of the European
      Association of Nuclear Medicine (EANM) and the North American consensus
      guidelines each provide recommendations of administered activities of
      radiopharmaceuticals in children, but there are substantial differences between
      these two guidelines. OBJECTIVE: For 12 commonly performed pediatric nuclear
      medicine studies, two established pediatric radiopharmaceutical administration
      guidelines were used to calculate updated radiation dose estimates and to compare
      the radiation exposure resulting from the recommendations of each of the
      guidelines. MATERIALS AND METHODS: Estimated radiation doses were calculated for
      12 common procedures in pediatric nuclear medicine using administered activities
      recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North
      American consensus guidelines for radiopharmaceutical administered activities in
      pediatrics. Based on standard models and nominal age-based weights, radiation
      dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult.
      The resulting effective doses were compared, with differences greater than 20%
      considered significant. RESULTS: Following either the EANM dosage card or the
      2010 North American guidelines, the highest effective doses occur with
      radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases,
      following the North American consensus guidelines would result in a substantially
      higher radiation dose. The guidelines of the EANM dosage card would lead to a
      substantially higher radiation dose in 39% of all cases, and in 62% of cases in
      which patients were age 5 years or younger. CONCLUSION: For 12 commonly performed
      pediatric nuclear medicine studies, updated radiation dose estimates can guide
      efforts to reduce radiation exposure and provide current information for
      discussing radiation exposure and risk with referring physicians, patients and
      families. There can be substantial differences in radiation exposure for the same
      procedure, depending upon which of these two guidelines is followed. This
      discordance identifies opportunities for harmonization of the guidelines, which
      may lead to further reduction in nuclear medicine radiation doses in children.

PMID- 25367356
TI  - Closing-opening wedge osteotomy for thoracolumbar traumatic kyphosis.
AB  - BACKGROUND: Surgical treatment modalities for post-traumatic kyphosis (PTK)
      remain controversial. Like vertebral column resection, closing-opening wedge
      osteotomy (COWO) can achieve satisfactory results for kyphosis with multiple
      etiologies. However, few studies have assessed this procedure for PTK. Our
      purpose was to evaluate the radiographic and clinical outcomes of COWO in a
      selected series of patients with PTK via a single posterior approach. METHODS: In
      this retrospective case series, seven patients with symptomatic PTK in the
      thoracolumbar spine were reviewed. Five patients underwent surgery at the time of
      initial injury, and the other two initially underwent conservative treatment. All
      seven patients underwent COWO procedures through a single posterior approach. The
      Cobb angle was assessed preoperatively, postoperatively, and at the final follow
      up. A visual analog scale (VAS) and the American Spinal Injury Association scale
      were used to evaluate back pain and neurological function preoperatively and at
      final follow-up, respectively. Operation-associated complications were also
      recorded. RESULTS: The mean follow-up period was 34.3 months (range, 24 to 43
      months). The mean kyphotic angle was significantly (P <0.05) reduced from 57.7
      degrees  (range, 36 degrees  to 100 degrees ) preoperatively to 8 degrees 
      postoperatively (range, -12 degrees  to 50 degrees ). The mean VAS improved from
      5.9 to 2.1 (P <0.05). Three patients exhibited improved neurological function.
      Bony fusion was achieved in all patients. No significant correction loss or
      permanent complication was noted. CONCLUSIONS: Though technically demanding, COWO
      via a single posterior approach can provide satisfactory outcomes for selected
      patients with PTK. Additional studies are required to improve patient selection
      and outcomes for this condition.

PMID- 25367357
TI  - Short-term parasite-infection alters already the biomass, activity and functional
      diversity of soil microbial communities.
AB  - Native parasitic plants may be used to infect and control invasive plants. We
      established microcosms with invasive Mikania micrantha and native Coix lacryma
      jobi growing in mixture on native soils, with M. micrantha being infected by
      parasitic Cuscuta campestris at four intensity levels for seven weeks to estimate
      the top-down effects of plant parasitism on the biomass and functional diversity
      of soil microbial communities. Parasitism significantly decreased root biomass
      and altered soil microbial communities. Soil microbial biomass decreased, but
      soil respiration increased at the two higher infection levels, indicating a
      strong stimulation of soil microbial metabolic activity (+180%). Moreover, a
      Biolog assay showed that the infection resulted in a significant change in the
      functional diversity indices of soil microbial communities. Pearson correlation
      analysis indicated that microbial biomass declined significantly with decreasing
      root biomass, particularly of the invasive M. micrantha. Also, the functional
      diversity indices of soil microbial communities were positively correlated with
      soil microbial biomass. Therefore, the negative effects on the biomass, activity
      and functional diversity of soil microbial community by the seven week long plant
      parasitism was very likely caused by decreased root biomass and root exudation of
      the invasive M. micrantha. 

PMID- 25367358
TI  - Changes in glomerular filtration rate after donation in living kidney donors: a
      single-center cohort study.
AB  - PURPOSE: A number of studies have reported on decline in glomerular filtration
      rate (GFR) after donation in Japanese living kidney donors. The purpose of the
      present study was to examine the clinicopathological factors associated with
      changes in GFR after donation in living kidney donors. METHODS: We reviewed the
      charts of living kidney donors (n = 294) and monitored estimated GFR (eGFR)
      values from the time of 0-h kidney biopsy until 3 years after donation. We
      assessed donor age, gender, body mass index, blood pressure, urinalysis, and
      several other clinical parameters including the severity of glomerulosclerosis
      and arteriosclerosis. RESULTS: The grade of arteriosclerosis in 0-h biopsy
      specimens was higher in the older donor group (57-76 years) than in the younger
      donor group (30-56 years). Mean donor eGFR at the time of the donation was 80.1
      +/- 13.6 ml/min/1.73 m(2). Most of the living kidney donors in this study
      developed stage 3 chronic kidney disease (CKD). The mean changes in eGFR at 1-3
      years after donation showed a steady state that was distinct from the generally
      accepted notion that GFR declines with age. Multivariate regression analyses
      showed that the changes in eGFR were negatively associated with age (r = -0.21, P
      < 0.001) and preoperative eGFR (r = -0.18, P < 0.001), but not associated with
      the grade of glomerulosclerosis and arteriosclerosis. CONCLUSION: Donor age and
      pre-GFR at the time of nephrectomy were associated with decline in kidney
      function in living kidney donors after donation. Most of the donors developed
      stage 3 CKD within 3 years after donation but without subsequent progression, at
      least for several years.

PMID- 25367359
TI  - Genetic variation of the transthyretin gene in wild-type transthyretin
      amyloidosis (ATTRwt).
AB  - Wild-type transthyretin amyloidosis (ATTRwt), typically diagnosed as congestive
      heart failure in elderly Caucasian men, features myocardial amyloid deposits of
      wild-type plasma protein transthyretin (TTR). ATTRwt is sporadic, its
      pathogenesis is poorly understood, and currently there are no biomarkers for
      diagnosis or prognosis. Genetic studies of variant-associated transthyretin
      amyloidosis have suggested that non-coding TTR gene variants modulate disease. We
      hypothesized that cis-acting regulatory elements in the TTR gene non-coding
      regions may modify expression, affecting ATTRwt onset and progression. We studied
      an ATTRwt cohort consisting of 108 Caucasian males ranging in age from 59 to 87
      years with cardiomyopathy due to wild-type TTR deposition; results were compared
      to 118 anonymous controls matched by age, sex, and race. Four predicted non
      coding regulatory regions and all exons in the TTR gene were sequenced using the
      Sanger method. Eleven common variants were identified; three variants were
      significantly associated with ATTRwt (p < 0.05), though only one, rs72922940,
      remained near significance (p corrected = 0.083) after multiple testing
      correction. Exon analyses demonstrated the occurrence of the p.G26S (G6S)
      polymorphism in 7 % of ATTRwt subjects and 12 % of controls; this variant was
      predicted to be a protective factor (p = 0.051). Four variants were significantly
      associated with age at onset and survival. In this first genetic study of a
      large, well-characterized cohort of ATTRwt, non-coding and coding variants
      associated with disease, age at onset, and survival were identified. Further
      investigation is warranted to determine the prevalence of these variants in
      ATTRwt, their regulatory function, and potential role in assessing disease risk. 

PMID- 25367361
TI  - NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in
      Brazilians.
AB  - Leprosy is a complex disease with phenotypes strongly influenced by genetic
      variation. A Chinese genome-wide association study (GWAS) depicted novel genes
      and pathways associated with leprosy susceptibility, only partially replicated by
      independent studies in different ethnicities. Here, we describe the results of a
      validation and replication study of the Chinese GWAS in Brazilians, using a
      stepwise strategy that involved two family-based and three independent case
      control samples, resulting in 3,614 individuals enrolled. First, we genotyped a
      family-based sample for 36 tag single-nucleotide polymorphisms (SNPs) of five
      genes located in four different candidate loci: CCDC122-LACC1, NOD2, TNFSF15 and
      RIPK2. Association between leprosy and tag SNPs at NOD2 (rs8057431) and CCDC122
      LACC1 (rs4942254) was then replicated in three additional, independent samples
      (combined OR(AA) = 0.49, P = 1.39e-06; OR(CC) = 0.72, P = 0.003, respectively).
      These results clearly implicate the NOD2 pathway in the regulation of leprosy
      susceptibility across diverse populations.

PMID- 25367362
TI  - Molecular insights into Rab7-mediated endosomal recruitment of core retromer:
      deciphering the role of Vps26 and Vps35.
AB  - Retromer, a peripheral membrane protein complex, plays an instrumental role in
      host of cellular processes by its ability to recycle receptors from endosomes to
      the trans-Golgi network. It consists of two distinct sub-complexes, a membrane
      recognizing, sorting nexins (SNX) complex and a cargo recognition, vacuolar
      protein sorting (Vps) complex. Small GTPase, Rab7 is known to recruit retromer on
      endosomal membrane via interactions with the Vps sub-complex. The molecular
      mechanism underlying the recruitment process including the role of individual Vps
      proteins is yet to be deciphered. In this study, we developed a FRET-based assay
      in HeLa cells that demonstrated the interaction of Rab7 with Vps35 and Vps26 in
      vivo. Furthermore, we showed that Rab7 recruits retromer to late endosomes via
      direct interactions with N-terminal conserved regions in Vps35. However, the
      single point mutation, which disrupts the interaction between Vps35 and Vps26,
      perturbed the Rab7-mediated recruitment of retromer in HeLa cells. Using
      biophysical measurements, we demonstrate that the association of Vps26 with Vps35
      resulted in high affinity binding between the Vps sub-complex and the activated
      Rab7 suggesting for a possible allosteric role of Vps26. Thus, this study
      provides molecular insights into the essential role of Vps26 and Vps35 in Rab7
      mediated recruitment of the core retromer complex. 

PMID- 25367363
TI  - Series asymmetric supercapacitors based on free-standing inner-connection
      electrodes for high energy density and high output voltage.
AB  - Asymmetric supercapacitors (ASCs) based on free-standing membranes with high
      energy density and high output voltage are reported. MnO(2) nanowire/carbon
      nanotube (CNT) composites and MoO(3) nanobelt/CNT composites are selected as the
      anode and the cathode materials of the devices, respectively. The ASC has a high
      volumetric capacitance of 50.2 F cm(-3) at a scan rate of 2 mV s(-1) and a high
      operation voltage window of 2.0 V. Especially, after a middle layer with an inner
      connection structure was inserted between the anode and the cathode, the output
      voltage of the whole device can achieve 4.0 V. The full cell of series ASCs
      (SASC) with an inner-connection middle layer has a high energy density of 28.6 mW
      h cm(-3) at a power density of 261.4 mW cm(-3), and exhibits excellent cycling
      performance of 99.6% capacitance retention over 10,000 cycles. This strategy of
      designing the hybridized structure for SASCs provides a promising route for next
      generation SCs with high energy density and high output voltage.

PMID- 25367364
TI  - Left ventricular hypertrophy: The relationship between the electrocardiogram and
      cardiovascular magnetic resonance imaging.
AB  - Conventional assessment of left ventricular hypertrophy (LVH) using the
      electrocardiogram (ECG), for example, by the Sokolow-Lyon, Romhilt-Estes or
      Cornell criteria, have relied on assessing changes in the amplitude and/or
      duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV
      mass have typically been validated by imaging with echocardiography or
      cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result
      of diverse etiologies, and LVH is also characterized by pathological changes in
      myocardial tissue characteristics on the genetic, molecular, cellular, and tissue
      level beyond a pure increase in the number of otherwise normal cardiomyocytes.
      For example, slowed conduction velocity through the myocardium, which can be due
      to diffuse myocardial fibrosis, has been shown to be an important determinant of
      conventional ECG LVH criteria regardless of LV mass. Myocardial tissue
      characterization by CMR has emerged to not only quantify LV mass, but also detect
      and quantify the extent and severity of focal or diffuse myocardial fibrosis,
      edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and
      myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry
      disease), or iron (siderosis). This can be undertaken using CMR techniques
      including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2* mapping,
      extracellular volume fraction (ECV) mapping, fat/water-weighted imaging, and
      diffusion tensor CMR. This review presents an overview of current and emerging
      concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an
      attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH.

PMID- 25367366
TI  - Esophageal Dysfunction in Friesian Horses: Morphological Features.
AB  - Megaesophagus appears to be more common in Friesian horses than in other breeds.
      A prevalence of approximately 2% was observed among Friesian horses presented to
      the Wolvega Equine Clinic and the Utrecht University Equine Clinic. In this
      study, morphologic changes in the esophagi of Friesian horses with megaesophagus
      were compared with those of 6 control horses. Of 18 horses with clinically
      observed megaesophagus, only 12 animals had esophageal dilation at necropsy,
      usually involving the thoracic portion. Muscular hypertrophy of the distal
      esophagus was present in only one-third of the affected horses, indicating that
      this change is not the most relevant cause of megaesophagus in Friesians.
      Increased deposition of clumped and disorganized collagen was present in these
      clinically affected horses mainly in the non-dilated portion of the esophagus. At
      necropsy, a decrease in neural elements and elastin was present principally in
      horses with megaesophagus. Mild degeneration and necrosis of the tunica
      muscularis along the entire length of the esophagus were present in clinically
      affected horses and encountered only rarely in control animals. There were no
      significant differences among affected and control horses with respect to
      inflammation, mineralization, or the number of cells of Cajal. The increased
      occurrence of megaesophagus in the Friesian breed compared with other horse
      breeds, together with the presence of abnormal collagen in very young foals,
      supports the hypothesis that megaesophagus is hereditary in Friesians. 

PMID- 25367360
TI  - Genome-wide association study for refractive astigmatism reveals genetic co
      determination with spherical equivalent refractive error: the CREAM consortium.
AB  - To identify genetic variants associated with refractive astigmatism in the
      general population, meta-analyses of genome-wide association studies were
      performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968);
      Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans
      aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the
      above three samples combined with a sample of Chinese subjects aged <25 years (N
      = 45,931). Participants were classified as cases with refractive astigmatism if
      the average cylinder power in their two eyes was at least 1.00 diopter and as
      controls otherwise. Genome-wide association analysis was carried out for each
      cohort separately using logistic regression. Meta-analysis was conducted using a
      fixed effects model. In the older European group the most strongly associated
      marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No
      other region reached genome-wide significance, and association signals were lower
      for the younger European group and Asian group. In the meta-analysis of all
      cohorts, no marker reached genome-wide significance: The most strongly associated
      regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and
      LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for
      spherical equivalent refractive error, the beta coefficients for genotype versus
      spherical equivalent, and genotype versus refractive astigmatism, were highly
      correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong
      genetic signals for refractive astigmatism; however, the TOX gene region
      previously identified in GWAS for spherical equivalent refractive error was the
      second most strongly associated region. Analysis of additional markers provided
      evidence supporting widespread genetic co-susceptibility for spherical and
      astigmatic refractive errors. 

PMID- 25367367
TI  - Immunohistochemical Characterization of Large Intestinal Adenocarcinoma in the
      Rhesus Macaque (Macaca mulatta).
AB  - In rhesus macaques, adenocarcinomas of either the ileocecal junction or colon are
      common spontaneous tumors in aging populations. The macaque tumors have similar
      gross and histologic characteristics compared with their human counterpart, but
      little is known regarding the immunohistochemical expression of proteins that are
      commonly implicated in the pathogenesis of these tumors in humans. We performed a
      retrospective review of 22 cases of large intestinal carcinoma in the rhesus
      macaque and evaluated the expression pattern of a panel of potentially
      prognostically significant proteins identified from human studies. Histologic
      characteristics of the tumors included abundant mucin deposition, transmural
      spread, and lymphatic invasion. All rhesus adenocarcinomas displayed altered
      expression of 1 or more of CD10, beta-catenin, sirtuin 1, cytokeratin 17, and p53
      compared with age-matched controls. Zymographic analysis of active matrix
      metalloproteinases 2 and 9 in the serum from 5 animals failed to reveal
      statistically significant differences between adenocarcinoma cases and controls.
      Based on the data presented herein, large intestinal carcinomas in the macaque
      share many histomorphologic and immunohistochemical similarities to large
      intestinal tumors in humans. Further validation of this animal model is
      considered important for the development of novel therapeutics and a better
      understanding of the pathogenesis. 

PMID- 25367365
TI  - Carbon monoxide down-regulates alpha4beta1 integrin-specific ligand binding and
      cell adhesion: a possible mechanism for cell mobilization.
AB  - BACKGROUND: Carbon monoxide (CO), a byproduct of heme degradation, is attracting
      growing attention from the scientific community. At physiological concentrations,
      CO plays a role as a signal messenger that regulates a number of physiological
      processes. CO releasing molecules are under evaluation in preclinical models for
      the management of inflammation, sepsis, ischemia/reperfusion injury, and organ
      transplantation. Because of our discovery that nitric oxide signaling actively
      down-regulates integrin affinity and cell adhesion, and the similarity between
      nitric oxide and CO-dependent signaling, we studied the effects of CO on integrin
      signaling and cell adhesion. RESULTS: We used a cell permeable CO releasing
      molecule (CORM-2) to elevate intracellular CO, and a fluorescent Very Late
      Antigen-4 (VLA-4, alpha4beta1-integrin)-specific ligand to evaluate the integrin
      state in real-time on live cells. We show that the binding of the ligand can be
      rapidly down-modulated in resting cells and after inside-out activation through
      several Galphai-coupled receptors. Moreover, cell treatment with hemin, a natural
      source of CO, resulted in comparable VLA-4 ligand dissociation. Inhibition of VLA
      4 ligand binding by CO had a dramatic effect on cell-cell interaction in a VLA
      4/VCAM-1-dependent cell adhesion system. CONCLUSIONS: We conclude that the CO
      signaling pathway can rapidly down-modulate binding of the VLA-4 -specific
      ligand. We propose that CO-regulated integrin deactivation provides a basis for
      modulation of immune cell adhesion as well as rapid cell mobilization, for
      example as shown for splenic monocytes in response to surgically induced ischemia
      of the myocardium.

PMID- 25367368
TI  - The quantum nature of skyrmions and half-skyrmions in Cu2OSeO3.
AB  - The Skyrme-particle, the skyrmion, was introduced over half a century ago in the
      context of dense nuclear matter. But with skyrmions being mathematical objects-
      special types of topological solitons--they can emerge in much broader contexts.
      Recently skyrmions were observed in helimagnets, forming nanoscale spin-textures.
      Extending over length scales much larger than the interatomic spacing, they
      behave as large, classical objects, yet deep inside they are of quantum nature.
      Penetrating into their microscopic roots requires a multi-scale approach,
      spanning the full quantum to classical domain. Here, we achieve this for the
      first time in the skyrmionic Mott insulator Cu2OSeO3. We show that its magnetic
      building blocks are strongly fluctuating Cu4 tetrahedra, spawning a continuum
      theory that culminates in 51 nm large skyrmions, in striking agreement with
      experiment. One of the further predictions that ensues is the temperature
      dependent decay of skyrmions into half-skyrmions.

PMID- 25367369
TI  - Topical intranasal corticosteroids and growth velocity in children: a meta
      analysis.
AB  - BACKGROUND: There is no consensus regarding the effects on growth velocity of
      intranasal topical corticosteroid (ITC) use in children. The objective of this
      study was to determine whether ITC use reduces growth velocity in children with
      allergic rhinitis (AR). METHODS: A literature search of the National Center for
      Biotechnology Information PubMed, EMBASE, SCOPUS, and Cochrane databases from
      January 1, 1988 to October 7, 2013. The study selection was composed of
      randomized clinical trials investigating ITC for treatment of AR in children (age
      <18 years of age) with appropriate controls. Studies must have included interval
      change in growth as an outcome. Two authors independently extracted data and
      assessed study quality. Eligible studies were pooled using a random-effects
      approach. RESULTS: Eight studies with 755 participants from 3 countries provided
      data for the meta-analysis (knemometry, n =342 participants; stadiometry, n =413
      participants). Study duration ranged from 2 to 4 weeks for trials evaluating
      knemometry outcomes, and 12 months for trials evaluating stadiometry outcomes.
      Age of participants ranged from 3 to 12 years. The pooled standardized mean
      difference showed that among studies using knemometry, mean growth was
      statistically significantly lower among children using ITC vs placebo (-.223
      mm/week; 95% confidence interval [CI], -0.429 to -0.017; p < 0.034).The pooled
      standardized mean difference showed that among studies using stadiometry, there
      was no significant growth difference among children using ITC vs placebo (-0.053
      cm/year; 95% CI, -0.491 to 0.385; p = 0.813). The limitations of this study were
      the difficulty in predicting longer-term or catch-up growth in children.
      CONCLUSION: Meta-analytic pooling of trials suggest that short-term ITC for the
      treatment of AR in children may decrease short-term growth velocity using
      knemometry; however, the effect on longer-term growth velocity as measured by
      stadiometry is unclear.

PMID- 25367370
TI  - Nanocomposites of phosphonic-acid-functionalized polyethylenes with inorganic
      quantum dots.
AB  - Insertion of diethyl vinyl phosphonates and free vinyl phosphonic acid,
      respectively, into [(P^O)Pd(Me)(dmso)] ((P^O) = kappa(2)-P,O-Ar2PC6H4SO2O with Ar
      = 2-MeOC6H4) (1-dmso) occurs in a 2,1- as well as 1,2-fashion, to form a four-and
      a five-membered chelate [(P^O)Pd{kappa(2)-C,O-CH(P(O)(OR)2)CH2CH3}] and
      [(P^O)Pd{kappa(2)-C,O-CH2CH(P(O)(OR)2)CH3}] (R = H, Et). No decomposition or
      other reactions of 1 by free phosphonic acid moieties occur. Copolymerization in
      a pressure reactor by 1-dmso yields linear random poly(ethylene-co-diethyl vinyl
      phosphonate) and poly(ethylene-co-vinyl phosphonic acid). In these
      copolymerizations, reversible coordination of the phosphonate moieties of free
      monomer as well as chelate formation by incorporated monomer retards chain growth
      as also evidenced by relative binding studies of diethyl phosphonate towards 1.
      Post-polymerization emulsification of poly(ethylene-co-vinyl phosphonic acid)
      together with CdSe/CdS quantum dots (QDs) yields submicron (ca. 50 nm from
      dynamic light scattering (DLS) and transmission electron microscopy (TEM))
      polymer particles with the QDs embedded in the functionalized polyethylene in a
      nonaggregated fashion. This embedding benefits the fluorescence behavior in terms
      of continuous emission and life-time as revealed by wide-field fluorescence
      measurements. These composite particle dispersions are employed as a
      "masterbatch" together with an aqueous high density polyethylene (HDPE)
      dispersion to generate thin films (by spin-coating) and bulk materials (from the
      melt), respectively, in which the inorganic nanoparticles remain highly disperse.

PMID- 25367371
TI  - Optimization of the genotyping-by-sequencing strategy for population genomic
      analysis in conifers.
AB  - Flexibility and low cost make genotyping-by-sequencing (GBS) an ideal tool for
      population genomic studies of nonmodel species. However, to utilize the potential
      of the method fully, many parameters affecting library quality and single
      nucleotide polymorphism (SNP) discovery require optimization, especially for
      conifer genomes with a high repetitive DNA content. In this study, we explored
      strategies for effective GBS analysis in pine species. We constructed GBS
      libraries using HpaII, PstI and EcoRI-MseI digestions with different multiplexing
      levels and examined the effect of restriction enzymes on library complexity and
      the impact of sequencing depth and size selection of restriction fragments on
      sequence coverage bias. We tested and compared UNEAK, Stacks and GATK pipelines
      for the GBS data, and then developed a reference-free SNP calling strategy for
      haploid pine genomes. Our GBS procedure proved to be effective in SNP discovery,
      producing 7000-11 000 and 14 751 SNPs within and among three pine species,
      respectively, from a PstI library. This investigation provides guidance for the
      design and analysis of GBS experiments, particularly for organisms for which
      genomic information is lacking.

PMID- 25367372
TI  - The house mouse (Mus musculus L.) exerts strong differential grain consumption
      preferences among hard red and white spring wheat (Triticum aestivum L.)
      varieties in a single-elimination tournament design.
AB  - Wheat (Triticum aestivum L.) plays a central role in the health and nutrition of
      humans. Yet, little is known about possible flavor differences among different
      varieties. We have developed a model system using the house mouse (Mus musculus
      L.) to determine feeding preferences as a prelude to extending results to human
      sensory analysis. Here, we examine the application of a single-elimination
      tournament design to the analysis of consumption preferences of a set of hard red
      and hard white spring wheat varieties. A single-elimination tournament design in
      this case pairs 2 wheat varieties and only 1 of the 2 is advanced to further
      tests. Preferred varieties were advanced until an overall "winner" was
      identified; conversely, less desirable varieties were advanced such that an
      overall "loser" was identified. Hollis and IDO702 were the winner and loser,
      respectively, for the hard red varieties, and Clear White 515 and WA8123 were the
      winner and loser, respectively, for the hard white varieties. When using the more
      powerful protocol of 14 mice and a 4-d trial, differences in mean daily
      consumption preferences of 2 varieties were separated at P-values as small as 2 *
      10(-8) . The single-elimination tournament design is an efficient means of
      identifying the most and least desirable varieties among a larger set of samples.
      One application for identifying the 2 extremes in preference within a group of
      varieties would be to use them as parents of a population to identify
      quantitative trait loci for preference. 

PMID- 25367373
TI  - Optical heating and temperature determination of core-shell gold nanoparticles
      and single-walled carbon nanotube microparticles.
AB  - The real-time temperature measurement of nanostructured materials is particularly
      attractive in view of increasing needs of local temperature probing with high
      sensitivity and resolution in nanoelectronics, integrated photonics, and
      biomedicine. Light-induced heating and Raman scattering of single-walled carbon
      nanotubes with adsorbed gold nanoparticles decorating silica microparticles are
      reported, by both green and near IR lasers. The plasmonic shell is used as
      nanoheater, while the single-walled carbon nanotubes are Raman active and serve
      as a thermometer. Stokes and Anti-Stokes Raman spectra of single-walled carbon
      nanotubes serve to estimate the effective light-induced temperature rise on the
      metal nanoparticles. The temperature rise is constant with time, indicating
      stability of the adsorption density. The effective temperatures derived from
      Stokes and Anti-Stokes intensities are correlated with those measured in a
      heating stage. The resolution of the thermal experiments in our study was found
      to be 5-40 K. 

PMID- 25367374
TI  - Structural basis of multivalent galactose-based dendrimer recognition by human
      galectin-7.
AB  - Galectins are evolutionarily conserved and ubiquitously present animal lectins
      with a high affinity for beta-galactose-containing oligosaccharides. To date, 15
      mammalian galectins have been identified. Their involvement in cell-cell and cell
      matrix interactions has highlighted their importance in signal transduction and
      other intracellular processes. Human galectin-7 (hGal-7) is a 15 kDa proto type
      galectin that forms a dimer in solution and its involvement in the stimulation
      and development of tumour growth has been reported. Previously, we reported the
      crystal structure of hGal-7 and its complex with galactose and lactose which
      provided insight into its molecular recognition and detailed interactions. Here,
      we present newly obtained high-resolution structural data on carbohydrate-based
      dendrons in complex with hGal-7. Our crystallographic data reveal how multivalent
      ligands interact with and form cross-links with these galectin molecules.
      Understanding how these dendrimeric compounds interact with hGal-7 would help in
      the design of new tools to investigate the recognition of carbohydrates by
      lectins.

PMID- 25367375
TI  - Plasmacytoid dendritic cells in hypertrophic discoid lupus erythematosus: an
      objective evaluation of their diagnostic value.
AB  - BACKGROUND: Hypertrophic discoid lupus erythematosus (HDLE), a rare variant of
      lupus skin disease, is difficult to distinguish from squamous neoplasms and
      certain dermatoses microscopically. Recently, recognition of the pathogenetic
      significance of plasmacytoid dendritic cells (PDCS) in cutaneous lupus
      erythematosus (LE) and of their patterns of distribution in different
      manifestations of the disease prompted us to study their diagnostic value in the
      context of HDLE. METHODS: Using immunohistochemistry (CD123) to label the cells,
      we examined their quantities and patterns of distribution in 27 tissue samples of
      HDLE from nine patients compared with 39 inflammatory and neoplastic control
      samples from 36 patients. RESULTS: Using three parameters pertaining to PDCs: (i)
      their representation of 10% or more of the inflammatory infiltrate, (ii) their
      arrangement in clusters of 10 cells or more and (iii) their presence at the
      dermoepidermal junction, we found them to have significant diagnostic value, with
      accuracies of 77%, 74% and 71%, respectively. CONCLUSIONS: This study supports
      the careful descriptive observations of previous authors in the field. It also
      lends validity to the diagnostic step of mapping, immunohistochemically, the
      density and distribution of PDCs in suspected cases of HDLE.

PMID- 25367376
TI  - Palladium-catalyzed anti-Markovnikov oxidation of terminal alkenes.
AB  - The palladium-catalyzed oxidation of alkenes, the Wacker-Tsuji reaction, is
      undoubtedly a classic in organic synthesis and provides reliable access to methyl
      ketones from terminal alkenes under mild reaction conditions. Methods that switch
      the selectivity of the reaction to provide the aldehyde product are desirable
      because of the access they provide to a valuable functional group, however such
      methods are elusive. Herein we survey both the methods which have been developed
      recently in achieving such selectivity and discuss common features and
      mechanistic insight which offers promise in achieving the goal of a general
      method for anti-Markovnikov-selective olefin oxidations. 

PMID- 25367379
TI  - A yield-associated gene TaCWI, in wheat: its function, selection and evolution in
      global breeding revealed by haplotype analysis.
AB  - KEY MESSAGE: Wheat anther-specific invertase genes were haplotyped in wheat.
      Strong allelic selection occurred during wheat polyploidization, domestication
      and breeding because of their association with yield traits. Plant invertase
      hydrolyzes sucrose into glucose and fructose. Cell wall invertase (CWI), one of
      the three types of invertase, is essential for plant development. Based on
      isolated TaCWI genes from chromosomes 4A, 5B and 5D, two SNPs were detected in
      the promoter region of TaCWI-4A, and four SNPs and two Indels were present in the
      TaCWI-5D gene. No polymorphism was detected in TaCWI-5B coding or promoter
      regions. CAPS markers caps4A and caps5D were developed to discriminate haplotypes
      of TaCWI-4A and TaCWI-5D. Marker/trait association analysis indicated that Hap-5D
      C at TaCWI-5D was significantly associated with higher thousand kernel weight
      (TKW) in 348 Chinese modern cultivars grown in multiple environments. Geographic
      distributions and changes over time of favored haplotypes showed that Hap-5D-C
      was the most frequent haplotype in modern cultivars and was strongly positively
      selected in six major wheat production regions worldwide. However, selection for
      haplotypes at TaCWI-4A was not so evident, possibly due to balancing effects of
      the two haplotypes on TKW and grain number per spike (GN). In rainfed production
      regions, Hap-4A-C was favored because it brought more seeds, but in well
      irrigated conditions, Hap-4A-T was favored in modern breeding because of higher
      TKW. Evolutionary analysis among wheat and its relatives showed that genetic
      diversity of TaCWI genes on chromosomes 4A and 5D declined dramatically in
      progression from the diploid level to modern polyploid cultivars. There was
      strong allelic selection during polyploidization, domestication and breeding.

PMID- 25367378
TI  - Genome-wide association study (GWAS) of carbon isotope ratio (delta13C) in
      diverse soybean [Glycine max (L.) Merr.] genotypes.
AB  - KEY MESSAGE: Using genome-wide association studies, 39 SNP markers likely tagging
      21 different loci for carbon isotope ratio (delta (13) C) were identified in
      soybean. Water deficit stress is a major factor limiting soybean [Glycine max
      (L.) Merr.] yield. Soybean genotypes with improved water use efficiency (WUE) may
      be used to develop cultivars with increased yield under drought. A collection of
      373 diverse soybean genotypes was grown in four environments (2 years and two
      locations) and characterized for carbon isotope ratio (delta(13)C) as a surrogate
      measure of WUE. Population structure was assessed based on 12,347 single
      nucleotide polymorphisms (SNPs), and genome-wide association studies (GWAS) were
      conducted to identify SNPs associated with delta(13)C. Across all four
      environments, delta(13)C ranged from a minimum of -30.550/00 to a maximum of 
      27.740/00. Although delta(13)C values were significantly different between the
      two locations in both years, results were consistent among genotypes across years
      and locations. Diversity analysis indicated that eight subpopulations could
      contain all individuals and revealed that within-subpopulation diversity, rather
      than among-subpopulation diversity, explained most (80%) of the diversity among
      the 373 genotypes. A total of 39 SNPs that showed a significant association with
      delta(13)C in at least two environments or for the average across all
      environments were identified by GWAS. Fifteen of these SNPs were located within a
      gene. The 39 SNPs likely tagged 21 different loci and demonstrated that markers
      for delta(13)C can be identified in soybean using GWAS. Further research is
      necessary to confirm the marker associations identified and to evaluate their
      usefulness for selecting genotypes with increased WUE.

PMID- 25367380
TI  - Training set optimization under population structure in genomic selection.
AB  - KEY MESSAGE: Population structure must be evaluated before optimization of the
      training set population. Maximizing the phenotypic variance captured by the
      training set is important for optimal performance. The optimization of the
      training set (TRS) in genomic selection has received much interest in both animal
      and plant breeding, because it is critical to the accuracy of the prediction
      models. In this study, five different TRS sampling algorithms, stratified
      sampling, mean of the coefficient of determination (CDmean), mean of predictor
      error variance (PEVmean), stratified CDmean (StratCDmean) and random sampling,
      were evaluated for prediction accuracy in the presence of different levels of
      population structure. In the presence of population structure, the most
      phenotypic variation captured by a sampling method in the TRS is desirable. The
      wheat dataset showed mild population structure, and CDmean and stratified CDmean
      methods showed the highest accuracies for all the traits except for test weight
      and heading date. The rice dataset had strong population structure and the
      approach based on stratified sampling showed the highest accuracies for all
      traits. In general, CDmean minimized the relationship between genotypes in the
      TRS, maximizing the relationship between TRS and the test set. This makes it
      suitable as an optimization criterion for long-term selection. Our results
      indicated that the best selection criterion used to optimize the TRS seems to
      depend on the interaction of trait architecture and population structure.

PMID- 25367382
TI  - Role of ultrasound in the management of diabetes in pregnancy.
AB  - The purpose of this review is to discuss the established role of ultrasound (US)
      in the management of pregnancy complicated by diabetes mellitus (DM), as well as
      new developments with regard to the use of US in this situation. We choose to
      explore the role of US in pregnancy complicated by DM in three areas: (1) Role of
      US in estimation of fetal weight. (2) Role of US in diagnosis of congenital
      malformation. (3) Role of US in monitoring diabetic pregnant patients. 

PMID- 25367381
TI  - Fine mapping of the qLOP2 and qPSR2-1 loci associated with chilling stress
      tolerance of wild rice seedlings.
AB  - KEY MESSAGE: Using leaf osmotic potential and plant survival rate as chilling
      tolerant trait indices, we identified two major quantitative trait loci qLOP2 and
      qPSR2 - 1 (39.3-kb region) and Os02g0677300 as the cold-inducible gene for these
      loci. Chilling stress tolerance (CST) at the seedling stage is an important trait
      affecting rice production in temperate climate and high-altitude areas. To
      identify quantitative trait loci (QTLs) associated with CST, a mapping population
      consisting of 151 BC(2)F(1) plants was constructed by using chilling-tolerant
      Dongxiang wild rice (Oryza rufipogon Griff.) as a donor parent and chilling
      sensitive indica as a recurrent parent. With leaf osmotic potential (LOP) and
      plant survival rate (PSR) as chilling-tolerant trait indexes, two major QTLs,
      qLOP2 (LOD = 3.8) and qPSR2-1 (LOD = 3.3), were detected on the long arm of
      chromosome 2 by composite interval mapping method in QTL Cartographer software,
      which explained 10.1 and 12.3% of the phenotypic variation, respectively. In
      R/QTL analyzed result, their major effects were also confirmed. Using molecular
      marker RM318 and RM106, qLOP2 and qPSR2-1 have been introgressed into chilling
      sensitive varieties (93-11 and Yuefeng) by marker-assisted selection procedure
      (MAS), which resulted in 16 BC(5)F(3) BILs that chilling tolerance have
      significantly enhanced compare with wild-type parents (P < 0.01). Therefore, two
      large segregating populations of 11,326 BC(4)F(2) and 8,642 BC(4)F(3) were
      developed to fine mapping of qLOP2 and qPSR2-1. Lastly, they were dissected to a
      39.3-kb candidate region between marker RM221 and RS8. Expression and sequence
      analysis results indicated that Os02g0677300 was a cold-inducible gene for these
      loci. Our study provides novel alleles for improving rice CST by MAS and
      contributes to the understanding of its molecular mechanisms.

PMID- 25367384
TI  - Formaldehyde-fixed brain tissue from spontaneously ill alpha-synuclein transgenic
      mice induces fatal alpha-synucleinopathy in transgenic hosts.

PMID- 25367383
TI  - Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to
      FTLD-TDP Type A.
AB  - Hippocampal sclerosis (HpScl) is frequent in frontotemporal lobar degeneration
      with TDP-43 pathology (FTLD-TDP), but it also occurs in dementia of the elderly
      with or without accompanying Alzheimer type pathology. HpScl has been
      hypothesized to be a neurodegenerative process given its association with TDP-43
      pathology, but this is still controversial. TDP-43 pathology is found in Lewy
      body disease (LBD), but no study has focused on the pathologic and genetic
      characteristics of HpScl in LBD. We found HpScl in 5.2% of 669 LBD cases (289
      transitional and 380 diffuse). Older age, higher Braak neurofibrillary tangle
      (NFT) stage, and presence of TDP-43 pathology were associated with HpScl. There
      was no difference in the frequency of HpScl between transitional and diffuse LBD,
      suggesting that Lewy-related pathology appears to have no direct association with
      HpScl. All HpScl cases had TDP-43 pathology consistent with Type A pattern. HpScl
      cases harbored genetic variation in TMEM106B that has been previously associated
      with FTLD-TDP. Interestingly, the severity of TDP-43-positive fine neurites in
      CA1 sector, a possible pathologic precursor of HpScl, was associated with the
      TMEM106B variant. These results demonstrate HpScl in LBD is a TDP-43
      proteinopathy and is similar to FTLD-TDP Type A. Furthermore, a subset of LBD
      cases without HpScl ("pre-HpScl") had similar pathologic and genetic
      characteristics to typical HpScl, suggesting that the spectrum of HpScl pathology
      may be wider than previously thought. Some cases with many extracellular NFTs
      also had a similar profile. We suggest that HpScl is "masked" in these cases.

PMID- 25367385
TI  - Autophagy in neuronal cells: general principles and physiological and
      pathological functions.
AB  - Autophagy delivers cytoplasmic components and organelles to lysosomes for
      degradation. This pathway serves to degrade nonfunctional or unnecessary
      organelles and aggregate-prone and oxidized proteins to produce substrates for
      energy production and biosynthesis. Macroautophagy delivers large aggregates and
      whole organelles to lysosomes by first enveloping them into autophagosomes that
      then fuse with lysosomes. Chaperone-mediated autophagy (CMA) degrades proteins
      containing the KFERQ-like motif in their amino acid sequence, by transporting
      them from the cytosol across the lysosomal membrane into the lysosomal lumen.
      Autophagy is especially important for the survival and homeostasis of postmitotic
      cells like neurons, because these cells are not able to dilute accumulating
      detrimental substances and damaged organelles by cell division. Our current
      knowledge on the autophagic pathways and molecular mechanisms and regulation of
      autophagy will be summarized in this review. We will describe the physiological
      functions of macroautophagy and CMA in neuronal cells. Finally, we will summarize
      the current evidence showing that dysfunction of macroautophagy and/or CMA
      contributes to neuronal diseases. We will give an overview of our current
      knowledge on the role of autophagy in aging neurons, and focus on the role of
      autophagy in four types of neurodegenerative diseases, i.e., amyotrophic lateral
      sclerosis and frontotemporal dementia, prion diseases, lysosomal storage
      diseases, and Parkinson's disease. 

PMID- 25367386
TI  - Hierarchically organized silica-titania monoliths prepared under purely aqueous
      conditions.
AB  - Hierarchically organized silica-titania monoliths were synthesized under purely
      aqueous conditions by applying a new ethylene glycol-modified single-source
      precursor, such as 3-[3-{tris(2-hydroxyethoxy)silyl}propyl]acetylacetone
      coordinated to a titanium center. The influence of the silicon- and titanium
      containing single-source precursor, the novel glycolated organofunctional silane,
      and the addition of tetrakis(2-hydroxyethyl)orthosilicate on the formation of the
      final porous network was investigated by SEM, TEM, nitrogen sorption, and
      SAXS/WAXS. In situ SAXS measurements were performed to obtain insight into the
      development of the mesoporous network during sol-gel transition. IR-ATR, UV/Vis,
      XPS, and XAFS measurements showed that up to a Si/Ti ratio of 35:1, well
      dispersed titanium centers in a macro-/mesoporous SiO2 network with a specific
      surface area of up to 582 m(2)  g(-1) were obtained. An increase in Ti content
      resulted in a decrease in specific surface area and a loss of the cellular
      character of the macroporous network. With a 1:1 Si/Ti ratio, silica-titania
      powders with circa 100 m(2)  g(-1) and anatase domains within the SiO2 matrix
      were obtained. 

PMID- 25367387
TI  - The medium and the message: fitting sound health promotion methodology into 160
      characters.
AB  - Text messaging health promotion projects continue to proliferate due to their
      relative low-cost, simplicity, non-intrusiveness, and proven effectiveness in
      several randomized controlled trials. In these past trials, participants have
      typically been recruited through traditional means, received the text messaging
      intervention, and then completed evaluation. In this issue of the Journal of
      Medical Internet Research, Sheoran et al have demonstrated how use of text
      messaging alone can be a feasible method for all three stages: recruitment,
      intervention, and evaluation. Use of text messages without any other modes of
      communication could be a key to population-level dissemination and wider uptake
      of health promotion messages. However, in the rush to utilize new technologies
      and in the brevity of 160 characters, it should not be forgotten that quality,
      rigour, and careful development remain essential in any health promotion
      practice. 

PMID- 25367388
TI  - Addressing the global need to combat multidrug resistance: carbohydrates may hold
      the key.

PMID- 25367389
TI  - Evolution of the activity cliff concept for structure-activity relationship
      analysis and drug discovery.

PMID- 25367390
TI  - Surface plasmon resonance--more than a screening technology: insights in the
      binding mode of sigma70:core RNAP inhibitors.
AB  - AIM: Antibiotic resistance has become a major health problem. The sigma(70):core
      interface of bacterial RNA polymerase is a promising drug target. Recently, the
      coiled-coil and lid-rudder-system of the beta' subunit has been identified as an
      inhibition hot spot. Materials & methods & Results: By using surface plasmon
      resonance-based assays, inhibitors of the protein-protein interaction were
      identified and competition with sigma(70) was shown. Effective inhibition was
      verified in an in vitro transcription and a sigma(70):core assembly assay. For
      one hit series, we found a correlation between activity and affinity. Mutant
      interaction studies suggest the inhibitors' binding site. CONCLUSION: Surface
      plasmon resonance is a valuable technology in drug design, that has been used in
      this study to identify and evaluate sigma(70):core RNA polymerase inhibitors.

PMID- 25367391
TI  - Cancer stem cells as a target population for drug discovery.
AB  - Cancer stem cells (CSCs) have been identified in a growing list of malignancies
      and are believed to be responsible for cancer initiation, metastasis and relapse
      following certain therapies, even though they may only represent a small fraction
      of the cells in a given cancer. Like somatic stem cells and embryonic stem cells,
      CSCs are capable of self-renewal and differentiation into more mature, less
      tumorigenic cells that make up the bulk populations of cancer cells. Elimination
      of CSCs promises intriguing therapeutic potential and this concept has been
      adopted in preclinical drug discovery programs. Herein we will discuss the
      progress of these efforts, general considerations in practice, major challenges
      and possible solutions. 

PMID- 25367393
TI  - Atheroprotective effects of (poly)phenols: a focus on cell cholesterol
      metabolism.
AB  - Collated observations from several epidemiological studies have demonstrated that
      dietary intake of (poly)phenols from nuts, coffee, cocoa, grapes, and berries may
      protect against the development of atherosclerosis. Whereas this beneficial
      activity has previously been linked mainly to antioxidant or anti-inflammatory
      properties, recently emerging data suggest mechanisms by which (poly)phenolic
      substances can modulate cellular lipid metabolism, thereby mitigating
      atherosclerotic plaque formation. In this review, both experimental studies and
      clinical trials investigating the atheroprotective effects of the most relevant
      dietary (poly)phenols are critically discussed. 

PMID- 25367392
TI  - Alternative approaches to Hsp90 modulation for the treatment of cancer.
AB  - Hsp90 is responsible for the conformational maturation of newly synthesized
      polypeptides (client proteins) and the re-maturation of denatured proteins via
      the Hsp90 chaperone cycle. Inhibition of the Hsp90 N-terminus has emerged as a
      clinically relevant strategy for anticancer chemotherapeutics due to the
      involvement of clients in a variety of oncogenic pathways. Several immunophilins,
      co-chaperones and partner proteins are also necessary for Hsp90 chaperoning
      activity. Alternative strategies to inhibit Hsp90 function include disruption of
      the C-terminal dimerization domain and the Hsp90 heteroprotein complex. C
      terminal inhibitors and Hsp90 co-chaperone disruptors prevent cancer cell
      proliferation similar to N-terminal inhibitors and destabilize client proteins
      without induction of heat shock proteins. Herein, current Hsp90 inhibitors, the
      chaperone cycle, and regulation of this cycle will be discussed. 

PMID- 25367395
TI  - Oxidative halogenation of cisplatin and carboplatin: synthesis, spectroscopy, and
      crystal and molecular structures of Pt(IV) prodrugs.
AB  - A series of Pt(IV) prodrugs has been obtained by oxidative halogenation of either
      cisplatin or carboplatin. Iodobenzene dichloride is a general reagent that
      cleanly provides prodrugs bearing axial chlorides without the need to prepare
      intervening Pt(IV) intermediates or handle chlorine gas. Elemental bromine and
      iodine afford Pt(IV) compounds as well, although in the case of the iodine
      mediated oxidation of carboplatin, an amido-bridged Pt(IV) side product also
      formed. A detailed analysis of the changes in spectroscopic and structural
      parameters induced by varying the axial halide is presented. A number of
      recurring motifs are observed in the solid state structures of these compounds.

PMID- 25367394
TI  - Specific-detection of clinical samples, systematic functional investigations, and
      transcriptome analysis reveals that splice variant MUC4/Y contributes to the
      malignant progression of pancreatic cancer by triggering malignancy-related
      positive feedback loops signaling.
AB  - BACKGROUND: MUC4 plays important roles in the malignant progression of human
      pancreatic cancer. But the huge length of MUC4 gene fragment restricts its
      functional and mechanism research. As one of its splice variants, MUC4/Y with
      coding sequence is most similar to that of the full-length MUC4 (FL-MUC4),
      together with alternative splicing of the MUC4 transcript has been observed in
      pancreatic carcinomas but not in normal pancreas. So we speculated that MUC4/Y
      might be involved in malignant progression similarly to FL-MUC4, and as a
      research model of MUC4 in pancreatic cancer. The conjecture was confirmed in the
      present study. METHODS: MUC4/Y expression was detected by real-time quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) using gene-specific
      probe in the clinic samples. The effects of MUC4/Y were observed by serial in
      vitro and in vivo experiments based on stable over-expressed cell model. The
      underlying mechanisms were investigated by sequence-based transcriptome analysis
      and verified by qRT-PCR, Western blot and enzyme-linked immunosorbent assays.
      RESULTS: The detection of clinical samples indicates that MUC4/Y is significantly
      positive-correlated with tumor invasion and distant metastases. Based on stable
      forced-expressed pancreatic cancer PANC-1 cell model, functional studies show
      that MUC4/Y enhances malignant activity in vitro and in vivo, including
      proliferation under low-nutritional-pressure, resistance to apoptosis, motility,
      invasiveness, angiogenesis, and distant metastasis. Mechanism studies indicate
      the novel finding that MUC4/Y triggers malignancy-related positive feedback loops
      for concomitantly up-regulating the expression of survival factors to resist
      adverse microenvironment and increasing the expression of an array of cytokines
      and adhesion molecules to affect the tumor milieu. CONCLUSIONS: In light of the
      enormity of the potential regulatory circuitry in cancer afforded by MUC4 and/or
      MUC4/Y, repressing MUC4 transcription, inhibiting post-transcriptional
      regulation, including alternative splicing, or blocking various pathways
      simultaneously may be helpful for controlling malignant progression. MUC4/Y-
      expression model is proven to a valuable tool for the further dissection of MUC4
      mediated functions and mechanisms.

PMID- 25367396
TI  - Combined effects of zooplankton grazing and dispersal on the diversity and
      assembly mechanisms of bacterial metacommunities.
AB  - Effects of dispersal and the presence of predators on diversity, assembly and
      functioning of bacterial communities are well studied in isolation. In reality,
      however, dispersal and trophic interactions act simultaneously and can therefore
      have combined effects, which are poorly investigated. We performed an experiment
      with aquatic metacommunities consisting of three environmentally different
      patches and manipulated dispersal rates among them as well as the presence or
      absence of the keystone species Daphnia magna. Daphnia magna reduced both local
      and regional diversity, whereas dispersal increased local diversity but decreased
      beta-diversity having no net effect on regional diversity. Dispersal modified the
      assembly mechanisms of bacterial communities by increasing the degree of
      determinism. Additionally, the combination of the D. magna and dispersal
      increased the importance of deterministic processes, presumably because predator
      tolerant taxa were spread in the metacommunity via dispersal. Moreover, the
      presence of D. magna affected community composition, increased community
      respiration rates but did not affect bacterial production or abundance, whereas
      dispersal slightly increased bacterial production. In conclusion, our study
      suggests that predation by a keystone species such as D. magna and dispersal
      additively influence bacterial diversity, assembly processes and ecosystem
      functioning. 

PMID- 25367397
TI  - Measuring progress with clinical governance development in New Zealand:
      perceptions of senior doctors in 2010 and 2012.
AB  - BACKGROUND: Clinical governance has become a core component of health policy and
      services management in many countries in recent years. Yet tools for measuring
      its development are limited. We therefore created the Clinical Governance
      Development Index (CGDI), aimed to measure implementation of expressed government
      policy in New Zealand. METHODS: We developed a survey which was distributed in
      2010 and again in 2012 to senior doctors employed in public hospitals. Responses
      to six survey items were weighted and combined to form the CGDI. Final scores for
      each of New Zealand's District Health Boards (DHBs) were calculated to compare
      performances between them as well as over time between the two surveys. RESULTS:
      New Zealand's overall performance in developing clinical governance improved
      between the two studies from 46% in 2010 to 54% in 2012 with marked differences
      by DHB. Statistically significant shifts in performance were evident on all but
      one CGDI item. CONCLUSIONS: The CGDI is a simple yet effective method which
      probes aspects of organisational commitment to clinical governance, respondent
      participation in organisational design, quality improvement, and teamwork. It
      could be adapted for use in other health systems.

PMID- 25367398
TI  - Optimization of inorganic carbon sources to improve the carbon fixation
      efficiency of the non-photosynthetic microbial community with different electron
      donors.
AB  - As the non-photosynthetic microbial community (NPMC) isolated from seawaters
      utilized inorganic carbon sources for carbon fixation, the concentrations and
      ratios of Na2CO3, NaHCO3, and CO2 were optimized by response surface methodology
      design. With H2 as the electron donor, the optimal carbon sources were 270 mg/L
      Na2CO3, 580 mg/L NaHCO3, and 120 mg/L CO2. The carbon fixation efficiency in
      response to total organic carbon (TOC) was up to 30.59 mg/L with optimal carbon
      sources, which was about 50% higher than that obtained with CO2 as the sole
      carbon source. The mixture of inorganic carbon sources developed a buffer system
      to prevent acidification or alkalization of the medium caused by CO2 or Na2CO3,
      respectively. Furthermore, CO2 and HCO3(-), the starting points of carbon
      fixation in the pathways of Calvin-Benson-Bassham and 3-hydroxypropionate cycles,
      were provided by the carbon source structure to facilitate carbon fixation by
      NPMC. However, in the presence of mixed electron donors composed of 1.25% Na2S,
      0.50% Na2S2O3, and 0.457% NaNO2, the carbon source structure did not exhibit
      significant improvement in the carbon fixation efficiency, when compared with
      that achieved with CO2 as the sole carbon source. The positive effect of mixed
      electron donors on inorganic carbon fixation was much higher than that of the
      carbon source structure. Nevertheless, the carbon source structure could be used
      as an alternative to CO2 when using NPMC to fix carbon in industrial processes. 

PMID- 25367399
TI  - Imaging the stereodynamics of methyl iodide photodissociation in the second
      absorption band: fragment polarization and the interplay between direct and
      predissociation.
AB  - The stereochemistry of methyl iodide photodissociation in the onset of the second
      absorption B-band has been studied using slice imaging of the CH3(nu = 0) and
      I*((2)P1/2) photoproducts. The stereodynamical data have been crucial to
      disentangle the photochemistry of methyl iodide in terms of the competition
      between direct dissociation and electronic predissociation. The origin of the B
      band has been established with high accuracy at 201.11 +/- 0.12 nm and a
      depolarization factor due to parent molecule rotation during predissociation has
      been found to be 0.29 +/- 0.06. Analysis of the semiclassical Dixon's bipolar
      moments extracted from the CH3(nu = 0) sliced images indicates that direct
      excitation to the A-band (3)A1 repulsive state in the vicinity of the origin of
      the B-band is remarkably enhanced by vibrational coupling between the electronic
      states involved at the conical intersection through in-plane vibrational motion
      of the molecule. 

PMID- 25367400
TI  - The ratio of glycated albumin to hemoglobin A1c measured in IFCC units accurately
      represents the glycation gap.
AB  - The glycation gap (G-gap: difference between measured hemoglobin A1c [A1C] and
      the value predicted by its regression on the fructosamine level) is stable and
      associated with diabetic complications. Measuring A1C level in International
      Federation of Clinical Chemistry (IFCC) units (A1C-SI; mmol/mol) and National
      Glycohemoglobin Standardization Program units (A1C-NGSP; %) and using glycated
      albumin (GA) level instead of fructosamine level for calculating the G-gap, we
      investigated whether the G-gap is better represented by GA/A1C ratio if expressed
      in SI units (GA/A1C-SI ratio) rather than in NGSP units (GA/A1C-% ratio). We
      examined 749 Japanese children with type 1 diabetes using simultaneous GA and A1C
      measurements. Of these, 369 patients were examined more than five times to assess
      the consistency of the G-gap and the GA/A1C ratio within individuals. The
      relationship of GA/A1C-% ratio to the corresponding A1C-NGSP was stronger than
      that of GA/A1C-SI ratio to A1C-IFCC. At enrollment, the inverse relationship
      between the GA/A1C-SI ratio and G-gap was highly significant (R(2) = 0.95)
      compared with that between the GA/A1C-% ratio and G-gap (R(2) = 0.69). A highly
      significant inverse relationship was also observed between the mean GA/A1C-SI
      ratio and the mean G-gaps obtained individually over time (R(2) = 0.95) compared
      with that using the corresponding A1C-NGSP (R(2) = 0.67). We conclude that the G
      gap is better represented by the GA/A1C-SI ratio. We propose the use of mean
      GA/A1C-SI ratios easily obtained individually over time as reference values in
      Japanese children with type 1 diabetes (6.75 +/- 0.60 [means +/- SD]). 

PMID- 25367401
TI  - Lateral caudal axial pattern flap in 13 dogs.
AB  - OBJECTIVE: To describe the frequency and extent of complications associated with
      lateral caudal axial pattern flaps used to cover large traumatic or excision skin
      defects on the dorsum, gluteal, and perineal region in 13 dogs. STUDY DESIGN:
      Case series. ANIMALS: Thirteen client-owned dogs. METHODS: Medical records from 8
      institutions were reviewed for dogs treated with a lateral caudal axial pattern
      flap, including cases in which the procedure was combined with other
      reconstructive techniques. The flap length relative to the tail length, location
      of tail skin incision, size and cause of the defect, and short- and long-term
      complications were recorded. RESULTS: Thirteen dogs were included, 11 with tumors
      and 2 with traumatic skin loss. The mean estimated length of the flap relative to
      tail length was 51% (range 33-70%). Four dogs had wound complications. This
      included 2 dogs with minor postoperative wound complications (mild distal
      dehiscence) that did not require surgical revision and 2 dogs with major
      complications that required surgical revision. Two of these 4 dogs had distal
      flap necrosis, one was revised surgically and one was managed conservatively. In
      these 2 dogs, the flap length was estimated as 80% and 65% of the tail length,
      respectively. At 30 days, flaps in all dogs were completely healed. No long-term
      complications were recorded in any dog. For some dogs, the reconstruction was not
      obvious, with only the change in hair direction and color noticeable. CONCLUSION:
      Lateral caudal axial pattern flap is a reconstructive option for gluteal, dorsal,
      and perineal skin defects in dogs. Distal flap necrosis and dehiscence due to
      wound infection occurred in 4 dogs that required additional wound care but not
      always surgical revision.

PMID- 25367402
TI  - The Initiative to Maximize Progress in Adolescent and Young Adult Cancer Therapy
      (IMPACT) Cohort Study: a population-based cohort of young Canadians with cancer.
AB  - BACKGROUND: Cancer is the leading cause of disease-related death in adolescents
      and young adults (AYA). Annual improvements in AYA cancer survival have been
      inferior to those observed in children and older adults. Prior studies of AYA
      with cancer have been limited by their focus on patients from select treatment
      centres, reducing generalizability, or by being population-based but lacking
      diagnostic and treatment details. There is a critical need to conduct population
      based studies that capture detailed patient, disease, treatment and system-level
      data on all AYA regardless of treatment location. METHODS/DESIGN: We will create
      a cohort of all AYA (aged 15-21 years) at the time of diagnosis with any
      malignancy between 1992 and 2011 in Ontario, Canada (n = 5,394). Subjects will be
      identified through the Ontario Cancer Registry and the final cohort will be
      expanded to include 2012 diagnoses, as these data become available. Detailed
      diagnostic, treatment and outcome data for those patients treated at a pediatric
      cancer centre will be provided by a population-based pediatric cancer registry (n
      = 1,030). For 15-18 year olds treated at adult centres (n = 923) and all 19-21
      year olds (n = 3396), trained abstractors will collect the comparable data
      elements from medical records. We will link these data to population-based
      administrative health data that include physician billings, hospitalizations and
      emergency room visits. This will allow descriptions of health care access and use
      prior to cancer diagnosis, and during and after treatment. DISCUSSION: The IMPACT
      cohort will serve as a platform for addressing questions that span the AYA cancer
      journey. These will include determining which factors influence where AYA receive
      care, the impact of locus of care on the types and intensity of cancer therapy,
      appropriateness of surveillance for disease recurrence, access to clinical
      trials, and receipt of palliative and survivor care. Findings using the IMPACT
      cohort have the potential to lead to changes in practice and cancer policy,
      reduce mortality, and improve quality of life for AYA with cancer. The IMPACT
      data platform will be a permanent resource, accessible to researchers across
      Canada.

PMID- 25367403
TI  - Mindfulness-based cancer recovery and supportive-expressive therapy maintain
      telomere length relative to controls in distressed breast cancer survivors.
AB  - BACKGROUND: Group psychosocial interventions including mindfulness-based cancer
      recovery (MBCR) and supportive-expressive group therapy (SET) can help breast
      cancer survivors decrease distress and influence cortisol levels. Although
      telomere length (TL) has been associated with breast cancer prognosis, the impact
      of these two interventions on TL has not been studied to date. METHODS: The
      objective of the current study was to compare the effects of MBCR and SET with a
      minimal intervention control condition (a 1-day stress management seminar) on TL
      in distressed breast cancer survivors in a randomized controlled trial. MBCR
      focused on training in mindfulness meditation and gentle Hatha yoga whereas SET
      focused on emotional expression and group support. The primary outcome measure
      was relative TL, the telomere/single-copy gene ratio, assessed before and after
      each intervention. Secondary outcomes were self-reported mood and stress
      symptoms. RESULTS: Eighty-eight distressed breast cancer survivors with a
      diagnosis of stage I to III cancer (using the American Joint Committee on Cancer
      (AJCC) TNM staging system) who had completed treatment at least 3 months prior
      participated. Using analyses of covariance on a per-protocol sample, there were
      no differences noted between the MBCR and SET groups with regard to the
      telomere/single-copy gene ratio, but a trend effect was observed between the
      combined intervention group and controls (F [1,84], 3.82; P = .054; eta(2)  =
      .043); TL in the intervention group was maintained whereas it was found to
      decrease for control participants. There were no associations noted between
      changes in TL and changes in mood or stress scores over time. CONCLUSIONS:
      Psychosocial interventions providing stress reduction and emotional support
      resulted in trends toward TL maintenance in distressed breast cancer survivors,
      compared with decreases in usual care.

PMID- 25367404
TI  - Anti-amnesic activity of Citrus aurantium flowers extract against scopolamine
      induced memory impairments in rats.
AB  - Alzheimer's disease (AD) is a progressive neurological disorder that mostly
      affects the elderly population. Learning and memory impairment as the most
      characteristic manifestation of dementia could be induced chemically by
      scopolamine, a cholinergic antagonist. Cholinergic neurotransmission mediated
      brain oxidative stress. Citrus aurantium (CA) has traditionally been used for the
      treatment of insomnia, anxiety and epilepsy. The present study was designed to
      investigate the effect of Citrus aurantium on scopolamine-induced learning and
      memory deficit in rats. Forty-two Wistar rats were divided into six equal groups.
      (1) Control (received saline), (2) SCOP (scopolamine at a dose of 1 mg/kg for 15
      days), (3) and (4) SCOP + CA (scopolamine and CA extract at doses of 300 and 600
      mg/kg per day for 15 days), (5) and (6) intact groups (CA extract at 300 and 600
      mg/kg per day for 15 days, respectively). Administration of CA flower extract
      significantly restored memory and learning impairments induced by scopolamine in
      the passive avoidance test and also reduced escape latency during trial sessions
      in the Morris water maze test. Citrus aurantium flower extract significantly
      decreased the serum malondialdehyde (MDA) levels. Citrus aurantium flower extract
      has repairing effects on memory and behavioral disorders produced by scopolamine
      and may have beneficial effects in the treatment of AD.

PMID- 25367405
TI  - Association of Catechol-O-methyltransferase val/met polymorphism with cognitive
      function in Gilles de la Tourette syndrome patients.
AB  - Gilles de la Tourette syndrome (GTS) is a kind of neuropsychiatric disorder with
      childhood onset. The cognitive dysfunction caused by GTS could affect the growth
      and learning of children and adolescents. The mechanism of cognitive functions
      was associated with dopaminergic system, thus we access the associations between
      polymorphism of some dopaminergic system-related genes including Catechol-O
      methyltransferase (COMT) met/val, Dopamine receptor D4 (DRD4) exon III 48 bp VNTR
      (variable number of tandem repeats), Interleukin 1 (IL-1) Ra 86 bp and IL-1beta
      exon 5, and cognitive functions in GTS patients. Genotyping analysis was
      performed through polymerase chain reaction (PCR). Test for cognitive functions
      of GTS patients included modified wisconsin card sorting test (WCST), trail
      making test, visual reproduction test, stroop test and verbal fluency test. The
      patients with COMT met/met genotype showed less perseverative errors in modified
      WCST test compared with patients with COMT val/val genotype (P < 0.05).
      Meanwhile, patients without allele val had better delayed memory in visual
      reproduction test, less errors in the stroop test and less perseverative errors
      in modified WCST test compared with patients with allele val (P < 0.05). However,
      no significant difference was found in cognitive functions among patients with
      different genotypes or alleles of polymorphisms of DRD4 exon III 48 bp VNTR, IL-1
      Ra 86 bp and IL-1beta exon 5 (P > 0.05). Polymorphism of COMT met/val was
      correlated with cognitive functions in GTS patients. This study provided basis
      for the analysis of molecular genetic pathology of cognitive dysfunctions in GTS.

PMID- 25367406
TI  - Arterial remodeling of basilar atherosclerosis in isolated pontine infarction.
AB  - Isolated pontine infarctions are usually classified as paramedian pontine
      infarction (PPI) and lacunar pontine infarction (LPI). Although they have
      different shapes and locations, some recent studies proved that they might both
      be associated with basilar artery atherosclerosis in pathogenesis. This study
      aimed to explore the difference of basilar artery remodeling between two subtypes
      of pontine infarctions. Patients with PPI or LPI were scanned by High-resolution
      MRI (HR-MRI). The MR images of patients with basilar artery atherosclerosis were
      further analyzed to measure the vessel, lumen and wall areas at different
      segments of basilar arteries. Stenosis rate and remodeling index were calculated
      according to which arterial remodeling was divided into positive, intermediate
      and negative remodeling. Vascular risk factors and remodeling-related features
      were compared between PPI and LPI, and also between patients with and without
      positive remodeling. 34 patients with PPI and 21 patients with LPI had basilar
      artery atherosclerosis identified by HR-MRI. Positive remodeling was dominant in
      LPI group while in PPI group, three subtypes of remodeling were equal. Patients
      with positive remodeling had higher levels of low-density lipoprotein and
      homocysteine. Positive remodeling of basilar artery might reflect the low
      stability of basilar atherosclerotic plaques, which was more closely associated
      with LPI than PPI. 

PMID- 25367407
TI  - Association of COMT Val158Met polymorphism with wearing-off susceptibility in
      Parkinson's disease.
AB  - In previous study, we have found the catechol-O-methyltransferase (COMT)
      Val158Met polymorphism may be associated with the risk of Parkinson's disease
      (PD) in Asians, especially Japanese population. In this study, we further
      evaluated the associations of PD wearing-off susceptibility with COMT
      polymorphisms. We carried out a retrieval of studies and included the relevant
      studies which met the criteria. After the data were extracted, the Stata software
      11.0 was used to analyse the genotype frequencies. A total of five studies were
      included. The pooled result indicated that genotype AA was significantly
      associated with the wearing-off risk of PD (AA vs. others: OR = 2.52, 95 % CI
      1.21-5.26, P = 0.013; AA vs. GA: OR = 2.51, 95 % CI 1.18-5.34, P = 0.017; AA vs.
      GG: OR = 2.17, 95 % CI 1.09-4.33, P = 0.027). The results also showed allele A
      was correlated with PD wearing-off risk (A vs. G: OR = 1.95, 95 % CI 1.18-3.22, P
      = 0.009). In conclusion, this study suggested that Val158Met polymorphisms in
      COMT may increase the risk of wearing-off. Further studies with larger sample
      sizes are needed to confirm our results.

PMID- 25367408
TI  - Clinical characteristics of haematological malignancy patients diagnosed with
      leukaemia cutis: Experience of a single centre.
AB  - BACKGROUND/OBJECTIVES: We evaluated the clinical characteristics of patients with
      haematological malignancies at our centre who were diagnosed with leukaemia cutis
      (LC). In addition, we describe the spectrum of other skin lesions, including,
      secondary skin malignancies and nonspecific benign skin lesions in haematological
      malignancy patients. METHODS: We defined 58 skin lesions that developed in 54
      inpatients hospitalised in the Department of Haematology, Trakya University
      Medical Faculty, Turkey. All skin lesions that developed in inpatients between
      2006 and 2012 had been evaluated by a dermatologist. The patients' clinical
      features, skin biopsy results and therapies were obtained from hospital files.
      The diagnosis of LC was based on clinical features and histopathological
      examinations of the skin biopsy. RESULTS: There were 11 patients with LC. Six
      (54.5%) had acute myeloblastic leukaemia. In nine patients (82%), LC was present
      at the initial presentation. Secondary skin malignancy was detected in 11
      patients (five basal cell carcinoma, four Kaposi's sarcoma, one squamous cell
      carcinoma, one malignant melanoma); and malignancy was present in two patients
      (18%) at the initial presentation. Nonspecific benign skin lesions, the most
      frequent of which were drug eruptions, were determined in 32 of our patients. LC
      had a significantly higher likelihood of being present at initial presentation
      than other skin lesions (P < 0.01). The median survival in LC patients was quite
      short (4.5 months). CONCLUSIONS: LC was usually diagnosed at the initial
      presentation of the patient or during the early course of the disease. Having LC
      was a poor prognostic factor.

PMID- 25367409
TI  - Clinical efficacy of tigecycline used as monotherapy or in combination regimens
      for complicated infections with documented involvement of multiresistant
      bacteria.
AB  - INTRODUCTION: Tigecycline is an established treatment option for infections with
      multiresistant bacteria (MRB). It retains activity against many strains with
      limited susceptibility to other antibiotics. Efficacy and safety of tigecycline
      as monotherapy or in combination regimens were investigated in a prospective
      noninterventional study involving 1,025 severely ill patients in clinical routine
      at 137 German hospitals. MATERIALS AND METHODS: Data on the full population have
      been published; our present analysis focuses on infections caused by MRB. The
      study population included patients with complicated infections, high disease
      severity (APACHE II > 15: 65 %) and high MRB prevalence. Most patients had
      comorbidities, including cardiovascular disease, renal insufficiency, and/or
      diabetes mellitus. Treatment success was defined as cure/improvement without
      requirement of further antibiotic therapy. RESULTS: Pathogens isolated from 215
      evaluable patients with documented MRB infections included 132 methicillin
      resistant Staphylococcus aureus (MRSA), 42 vancomycin-resistant Enterococci (VRE)
      and 67 Gram-negative extended beta-lactamase (ESBL) producers. Of the MRB
      subpopulation, 140 patients received tigecycline monotherapy, 75 were treated
      with combination regimens. High overall clinical success rates were recorded for
      MRB infections treated with tigecycline alone (94 %) or in combinations (88 %);
      in detail intraabdominal infections (monotherapy: 90 %; combinations: 93 %),
      skin/soft tissue infections (93; 100 %), community-acquired pneumonia (100; 100
      %), hospital-acquired pneumonia (94,7; 72,7 %), diabetic foot infections (89; 33
      %), blood stream infections (100; 100 %) and multiple-site infections (92; 71 %).
      CONCLUSIONS: Tigecycline achieved high clinical success rates in patients with
      documented infections involving MRB strains despite high disease severity. These
      results add to the evidence indicating that tigecycline is a valuable therapeutic
      option for complicated infections in severely ill patients with a high likelihood
      of multidrug-resistant pathogen involvement.

PMID- 25367410
TI  - Clinical characteristics of Raoultella ornithinolytica bacteremia.
AB  - PURPOSE: Raoultella ornithinolytica is not well known as a clinical pathogen. We
      performed a retrospective review of R. ornithinolytica bacteremia to investigate
      its clinical features, antimicrobial susceptibility, and overall patient
      outcomes. METHODS: R. ornithinolytica bacteremia cases were collected from an
      electronic database of all cases of bacteremia over a 10-year period. Medical
      records were retrospectively reviewed. Demographic data, clinical information,
      the presence of underlying comorbidities, the results of antimicrobial
      susceptibility testing, and the antimicrobial regimen administered were
      investigated. RESULTS: R. ornithinolytica was isolated from blood culture
      specimens in 16 cases. The majority of these patients had an underlying malignant
      condition of advanced stage (15 patients, 94 %). Seven of these patients had a
      solid tumor with lesions or metastases that extended to the bile duct or biliary
      tract. Neutropenic fever following hematologic stem cell transplantation was
      found in three cases. No resistance to piperacillin/tazobactam or imipenem was
      found. Four cases showed resistance to cefoxitin, while one of these cases showed
      resistance to multiple cephalosporins. In overall outcomes, seven patients (44 %)
      did not recover from the infection and subsequently expired. CONCLUSIONS: R.
      ornithinolytica bacteremia occurs mainly in patients with underlying
      malignancies. The overall outcome was not favorable, despite favorable
      antimicrobial susceptibility test results. The findings of this study contradict
      those of other studies that demonstrated that infection from Raoultella species
      have good prognoses.

PMID- 25367411
TI  - Characterization of cerebral microbleeds in idiopathic Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) have been extensively studied
      in healthy controls and patients with cerebrovascular disease and Alzheimer's
      disease. Our aim was to characterize the clinical and radiological features of
      CMBs in idiopathic Parkinson's disease (IPD). METHODS: This cross-sectional study
      included consecutive parkinsonian patients who attended the authors' movement
      disorders clinic from March 2010 to February 2012 and underwent a standard
      magnetic resonance imaging (MRI) protocol with gradient recalled echo taken with
      a 3 T MRI machine. RESULTS: Amongst parkinsonian disorders, CMBs were most common
      in vascular parkinsonism (VP) (56%) and least common in IPD (17.7%). In IPD, CMBs
      were significantly associated with white matter hyperintensities and concurrent
      lacunar infarctions. The presence of CMBs had no effect on various cognitive
      domains in IPD. IPD with CMBs was discriminated from VP by clinical and
      neuroimaging findings: frequencies of motor subtypes were similar between IPD
      with and without CMBs, whereas all VP patients were the postural-instability gait
      difficulty type. In 90.9% of the IPD cases with CMBs, the numbers of CMBs were
      three or less, whereas the numbers of CMBs exceeded three in 50% of the cases of
      VP and exceeded 10 in 31.3% of the cases (P < 0.001). The topography of the CMBs
      in IPD was also different from that in VP (P < 0.01). CONCLUSIONS: Cerebral
      microbleeds are not rare in IPD, and IPD with CMBs does not appear to be a form
      of VP. Further studies in larger populations are needed to elucidate the clinical
      implications of CMBs in terms of prognoses and cognitive changes in IPD.

PMID- 25367412
TI  - Preservation of anemia control and weekly ESA dosage after conversion from PEG
      Epoetin beta to darbepoetin alfa in adult hemodialysis patients: the TRANSFORM
      study.
AB  - INTRODUCTION: There is scant real-world information on switching treatment for
      anemia associated with chronic kidney disease (CKD) from methoxy polyethylene
      glycol-epoetin beta (PEG-Epo) to darbepoetin alfa (DA). TRANSFORM was a multi
      center, observational study designed to describe the time course of hemoglobin
      (Hb) concentration (primary outcome measure) and other parameters of clinical
      management of anemia in European hemodialysis patients in clinical practice
      before and after a switch from PEG-Epo to DA. METHODS: Eligible subjects were
      adult patients with CKD dialyzed at European dialysis centers for >=26 weeks and
      treated with PEG-Epo for >=14 weeks immediately prior to being switched to DA and
      no earlier than January 2011. Erythropoiesis-stimulating agent doses and Hb
      values were recorded for the 14-week pre-switch and 26-week post-switch periods.
      RESULTS: Of the 1,027 eligible patients enrolled at 42 hemodialysis centers in 7
      European countries, 785 were included in analyses. Mean (95% confidence interval
      [CI]) Hb was generally stable: 11.19 (11.11, 11.26), 11.48 (11.40, 11.57), and
      11.29 (11.20, 11.37) g/dL at month -1 pre-switch and months 3 and 6 post-switch,
      respectively. The geometric mean (95% CI) PEG-Epo dose at month -1 was 27.4
      (26.0, 28.8) ug/week; DA dose was 29.4 (27.9, 30.9), 23.3 (21.9, 24.9), and 25.6
      (24.1, 27.1) ug/week at months 1, 4, and 6, respectively. The geometric mean (95%
      CI) dose ratio at switching was 1.06 (1.01, 1.11). When stratifying by dose-ratio
      categories <0.8, 0.8-1.2, and >1.2 at switching, mean DA dose and Hb converged
      within narrow ranges by month 6 post-switch: 23.9-27.0 ug/week and 11.1-11.5
      g/dL, respectively. Hb excursions <10 g/dL were less frequent post-switch versus
      pre-switch. CONCLUSION: Mean Hb values remained within a narrow range following
      switching from PEG-Epo to DA in this population of hemodialysis patients. Time
      trends of mean Hb and DA dose indicate that physicians titrated DA doses post
      switch, to attain Hb concentrations comparable to those attained pre-switch with
      PEG-Epo.

PMID- 25367413
TI  - Azithromycin Can Prolong QT Interval and Suppress Ventricular Contraction, but
      Will Not Induce Torsade de Pointes.
AB  - Azithromycin has been reported to increase the risk of death from cardiovascular
      causes among patients with high baseline risk. Since the information is still
      limited to bridge the gap between electrophysiological properties of azithromycin
      in vitro and cardiac death in patients, we initially assessed its
      electropharmacological effects in doses of 3 and 30 mg/kg, i.v., with the
      halothane-anesthetized dogs (n = 4). The low dose provided 5.2 times higher than
      the therapeutic concentration, whereas the high dose attained 17.0 times higher.
      The high dose delayed the ventricular repolarization in a reverse use-dependent
      manner, reflecting blockade of the rapid component of delayed rectifier K(+)
      current, and the potency was relatively weak; namely, maximum change in QTc was
      +20 ms (+5.6%). The high dose also induced the negative inotropic effect possibly
      through Ca(2+) channel-independent pathway. In order to clarify proarrhythmic
      risk, 30 mg/kg, i.v., of azithromycin was examined with the chronic
      atrioventricular block dogs (n = 4). Azithromycin neither induced torsade de
      pointes nor affected beat-to-beat variability of repolarization. Thus,
      azithromycin can be considered to lack proarrhythmic potential, but caution has
      to be paid on its use for patients with left ventricular dysfunction.

PMID- 25367414
TI  - Effect of amphiphilic PCL-PEG nano-micelles on HepG2 cell migration.
AB  - Uptake of nanoparticles (NPs) affects cell migration but the mechanism remains
      poorly understood. In this study, the amphiphilic block PCL-PEG nano-micelles
      with well-controlled hydrophilic/hydrophobic chains were used to investigate the
      effect of internalized nano-micelles on cancer cell migration. Our results
      indicated that the nano-micelles with medium PCL and PEG chains increased
      expression of Rho GTPases and impeded focal adhesion components. This could
      enhance Hep G2 cell motility. The nano-micelles with large PCL and PEG chains
      showed lower Rho GTPase levels and higher FA components. This is consistent with
      slower cell migration. Understanding the mechanism of NPs regulating cell
      behaviors may help the design of efficient drug delivery systems based on polymer
      micelles. 

PMID- 25367416
TI  - Nitrogen-converting communities in aerobic granules at different hydraulic
      retention times (HRTs) and operational modes.
AB  - This study determined how the activity and number of nitrogen-converting
      microorganisms varied with changes in hydraulic retention time (HRT) and the
      operating regime of aerobic granular sequencing batch reactors (GSBRs) treating
      high-nitrogen wastewater. Continuously aerated (O-mode) GSBRs were operated at
      HRTs of 10-, 13- and 19-h. Then the same reactors were operated at identical HRTs
      but the cycles started with an anoxic phase (A/O mode). To investigate the
      microbial communities, DNA- and RNA-based relative real-time PCR was used. In all
      experimental reactors ammonium was fully removed with a removal rate up to 75 mg
      N-NH4 (+)/(L.h), and nitrification efficiency was above 90 %. The efficiency of
      the removal of oxidized nitrogen forms decreased with the lengthening of HRT. The
      study found that variable oxic conditions (A/O mode) in the GSBR cycle stimulated
      the simultaneous activity of ammonium oxidizing bacteria (AOB), N2O-reducers, and
      Anammox bacteria in aerobic granules. With both modes, the activity of nitrogen
      converting bacteria was highest with a 13-h HRT. Shortening HRT, resulted in
      higher chemical oxygen demand and nitrogen loadings, which favored the growth of
      Anammox microorganisms in granules and caused a decrease in the number of AOB.
      With all HRTs, the number of Anammox microorganisms was about 1.5-times higher in
      A/O mode than in O mode. 

PMID- 25367415
TI  - Evaluation of a German version of the tonsil and adenoid health status
      instrument.
AB  - BACKGROUND: To create and validate a German version of the Tonsil and Adenoid
      Health Status Instrument (TAHSI) for evaluation of tonsillectomy outcome in adult
      patients with chronic or recurrent tonsillitis. SUBJECTS AND METHODS: 46 healthy
      volunteers were assessed twice in a 6 week interval with the TAHSI questionnaire.
      Their results were compared with 45 patients suffering from chronic tonsillitis
      before tonsillectomy and 6 months following surgery. For internal consistency,
      Cronbach's alpha was calculated; to identify normal score values, the optimum
      cutoff between healthy and diseased individuals was identified with receiver
      operating characteristic analysis; and responsiveness was assessed using Guyatt's
      Responsiveness Index (GRI). RESULTS: Cronbach's alpha for all questions was 0.92.
      Test- retest intraclass correlation coefficient was 0.89 (95% confidence interval
      0.80-0.94 p < 0.001). Mean score for the healthy individuals was 7.0 (95%
      confidence interval 4.2-9.7). The optimum cut off score between healthy and
      diseased was 20 with a sensitivity of 80% and a specificity of 90% to
      differentiate controls from tonsillectomy patients. CONCLUSION: The TAHSI
      performed well in this validation tests and is considered a favorable instrument
      to evaluate the effectiveness of tonsillectomy in adults with chronic or
      recurrent tonsillitis.

PMID- 25367418
TI  - Thoracic outlet syndrome: a congenital case manifesting in middle age.

PMID- 25367417
TI  - Purification and characterization of secretory serine protease from necrotrophic
      oomycete, Pythium myriotylum Dreschler.
AB  - Progressive increase in extracellular proteolytic activity with respect to growth
      was detected in cultures of necrotrophic oomycete Pythium myriotylum Dreschler
      with maximum activity detected at stationary phase of growth. The secretory
      protease from P. myriotylum designated, spPm1 was purified to homogeneity giving
      a single band of 47 kDa molecular mass on non-reducing SDS-PAGE and exhibiting
      caseinolytic activity in the zymogram. Under reducing conditions, an additional
      band of 27.0 kDa molecular size observed was subjected to matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) analysis.
      Resulting peptide identified as an autolytic product and generated under reducing
      conditions on SDS-PAGE, showed homology to domains of oomycete effector
      molecules. spPm1 retained proteolytic activity over broad pH (5.0-12.0) and
      temperature (10-80  degrees C) ranges with optimal pH and temperature at 8.0 and
      60  degrees C respectively. spPm1 was identified as a serine protease following
      experiments with inhibitors specific to various protease groups. spPm1 displayed
      high stability to surfactants, organic solvents, oxidizing agents and to metal
      ion chelator, EDTA. Kinetic parameters, Km and Vmax were determined as 0.04 mM
      and 7.52 U min(-1) mg(-1) respectively. Preferential hydrolysis of synthetic
      fluorogenic substrate, SAAPPPA (N-succinyl-L-alanyl-alanyl-proline-phenylalanine
      p-nitroanilide) confirmed spPm1 as belonging to subtilisin serine protease
      family. The excellent stability of spPm1 protease characterized from P.
      myriotylum is discussed with respect to its potential industrial applications. 

PMID- 25367420
TI  - Whose body is this?

PMID- 25367419
TI  - Time trends in symptoms of mental illness in children and adolescents in Canada.
AB  - BACKGROUND: Existing research and media reports convey conflicting impressions of
      trends in the prevalence of mental illness. We sought to investigate trends in
      the prevalence of symptoms of mental illness in a large population-based cohort
      of Canadian children and adolescents. METHODS: We obtained population-based data
      from the National Longitudinal Survey of Children and Youth. Every 2 years,
      participants completed self-reported measures of mental illness indicators,
      including conduct disorder, hyperactivity, indirect aggression, suicidal
      behaviour, and depression and anxiety. We analyzed trends in mean scores over
      time using linear regression. RESULTS: We evaluated 11 725 participants aged 10
      11 years from cycles 1 (1994/95) through 6 (2004/05), 10 574 aged 12-13 years
      from cycles 2 (1996/97) through 7 (2006/07), and 9835 aged 14-15 years from
      cycles 3 (1998/99) through 8 (2008/09). The distribution of scores on depression
      and anxiety, conduct and indirect aggression scales remained stable or showed
      small decreases over time for participants of all ages. The mean hyperactivity
      score increased over time in participants aged 10-11 years (change per 2-year
      cycle: 0.16, 95% CI 0.02 to 0.12) and those aged 12-13 years (0.13, 95% CI 0.09
      to 0.18). Over time, fewer participants aged 12-13 years (0.40% per cycle, 95% CI
      -0.78 to -0.07) and aged 14-15 years (0.56% per cycle, 95% CI -0.91 to -0.23)
      reported attempting suicide in the previous 12 months. INTERPRETATION: With the
      exception of hyperactivity, the prevalence of symptoms of mental illness in
      Canadian children and adolescents has remained relatively stable from 1994/95 to
      2008/09. Conflicting reports of escalating rates of mental illness in Canada may
      be explained by differing methodologies between studies, an increase in treatment
      seeking behaviour, or changes in diagnostic criteria or practices.

PMID- 25367421
TI  - Huge reorg of Nova Scotia's health system.

PMID- 25367422
TI  - All provinces can now sue big tobacco.

PMID- 25367423
TI  - Call for Ebola medics falls on deaf ears: MSF.

PMID- 25367424
TI  - 10 health stories that mattered this week: Oct. 27-31.

PMID- 25367425
TI  - Medical education needs digital boost.

PMID- 25367426
TI  - Spontaneous deep vein thrombosis in the upper extremity of a 45-year-old woman.

PMID- 25367427
TI  - What really matters in end-of-life discussions? Perspectives of patients in
      hospital with serious illness and their families.
AB  - BACKGROUND: The guideline-recommended elements to include in discussions about
      goals of care with patients with serious illness are mostly based on expert
      opinion. We sought to identify which elements are most important to patients and
      their families. METHODS: We used a cross-sectional study design involving
      patients from 9 Canadian hospitals. We asked older adult patients with serious
      illness and their family members about the occurrence and importance of 11
      guideline-recommended elements of goals-of-care discussions. In addition, we
      assessed concordance between prescribed goals of care and patient preferences,
      and we measured patient satisfaction with goals-of-care discussions using the
      Canadian Health Care Evaluation Project (CANHELP) questionnaire. RESULTS: Our
      study participants included 233 patients (mean age 81.2 yr) and 205 family
      members (mean age 60.2 yr). Participants reported that clinical teams had
      addressed individual elements of goals-of-care discussions infrequently (range
      1.4%-31.7%). Patients and family members identified the same 5 elements as being
      the most important to address: preferences for care in the event of life
      threatening illness, values, prognosis, fears or concerns, and questions about
      goals of care. Addressing more elements was associated with both greater
      concordance between patients' preferences and prescribed goals of care, and
      greater patient satisfaction. INTERPRETATION: We identified elements of goals-of
      care discussions that are most important to older adult patients in hospital with
      serious illness and their family members. We found that guideline-recommended
      elements of goals-of-care discussions are not often addressed by health care
      providers. Our results can inform interventions to improve the determination of
      goals of care in the hospital setting.

PMID- 25367428
TI  - Lichen rehydration in heavy metal-polluted environments: Pb modulates the
      oxidative response of both Ramalina farinacea thalli and its isolated microalgae.
AB  - Lichens are adapted to desiccation/rehydration and accumulate heavy metals, which
      induce ROS especially from the photobiont photosynthetic pigments. Although their
      mechanisms of abiotic stress tolerance are still to be unravelled, they seem
      related to symbionts' reciprocal upregulation of antioxidant systems. With the
      aim to study the effect of Pb on oxidative status during rehydration, the
      kinetics of intracellular ROS, lipid peroxidation and chlorophyll
      autofluorescence of whole Ramalina farinacea thalli and its isolated microalgae
      (Trebouxia TR1 and T. TR9) was recorded. A genetic characterization of the
      microalgae present in the thalli used was also carried out in order to assess
      possible correlations among the relative abundance of each phycobiont, their
      individual physiological responses and that of the entire thallus. Unexpectedly,
      Pb decreased ROS and lipid peroxidation in thalli and its phycobionts, associated
      with a lower chlorophyll autofluorescence. Each phycobiont showed a particular
      pattern, but the oxidative response of the thallus paralleled the TR1's, agreeing
      with the genetic identification of this strain as the predominant phycobiont. We
      conclude that: (1) the lichen oxidative behaviour seems to be modulated by the
      predominant phycobiont and (2) Pb evokes in R. farinacea and its phycobionts
      strong mechanisms to neutralize its own oxidant effects along with those of
      rehydration. 

PMID- 25367429
TI  - Separating sensitivity from exposure in assessing extinction risk from climate
      change.
AB  - Predictive frameworks of climate change extinction risk generally focus on the
      magnitude of climate change a species is expected to experience and the potential
      for that species to track suitable climate. A species' risk of extinction from
      climate change will depend, in part, on the magnitude of climate change the
      species experiences, its exposure. However, exposure is only one component of
      risk. A species' risk of extinction will also depend on its intrinsic ability to
      tolerate changing climate, its sensitivity. We examine exposure and sensitivity
      individually for two example taxa, terrestrial amphibians and mammals. We examine
      how these factors are related among species and across regions and how explicit
      consideration of each component of risk may affect predictions of climate change
      impacts. We find that species' sensitivities to climate change are not congruent
      with their exposures. Many highly sensitive species face low exposure to climate
      change and many highly exposed species are relatively insensitive. Separating
      sensitivity from exposure reveals patterns in the causes and drivers of species'
      extinction risk that may not be evident solely from predictions of climate
      change. Our findings emphasise the importance of explicitly including sensitivity
      and exposure to climate change in assessments of species' extinction risk. 

PMID- 25367431
TI  - EpCAM is decreased but is still present in uterine epithelial cells during early
      pregnancy in the rat: potential mechanism for maintenance of mucosal integrity
      during implantation.
AB  - The non-receptive uterine luminal epithelium forms a polarised epithelial
      barrier, protective against potential pathogenic assault from the external
      environment and invasion by the blastocyst. However, during the window of
      implantation, the uterine luminal epithelial cells (UECs) transition to a
      receptive state by dismantling many of their intercellular and cell-matrix
      adhesions in preparation for epithelial detachment and subsequent blastocyst
      implantation. The present study investigated the presence and regulation of the
      intercellular adhesion protein, Epithelial Cell Adhesion Molecule (EpCAM) during
      early pregnancy in the rat to understand its role in the transition to
      receptivity. Immunofluorescence and western blotting analysis were used to study
      EpCAM expression in normal pregnancy, hormone replacement studies and
      pseudopregnancy. EpCAM was abundantly expressed and localised to the uterine
      luminal and glandular epithelium during the non-receptive state but decreased to
      lower but still observable levels around the time of implantation. This decrease
      was not dependent on ovarian hormones or the blastocyst. Further, EpCAM
      colocalised with but did not associate with its frequent binding partner, Tumour
      necrosis factor alpha (TNFalpha)-converting enzyme, also known as A Disintegrin
      And Metalloprotease 17 (TACE/ADAM17), at the time of fertilisation. These results
      suggest that, prior to implantation, EpCAM mediates intercellular adhesion in the
      uterine epithelium, but that, during implantation when UECs lose the majority of
      their intercellular and cell-matrix adhesions, EpCAM levels are decreased but
      still present for the maintenance of mucosal integrity. 

PMID- 25367432
TI  - Proton intercalated two-dimensional WO3 nano-flakes with enhanced charge-carrier
      mobility at room temperature.
AB  - Quasi two-dimensional (Q2D) semiconducting metal oxides with enhanced charge
      carrier mobility hold tremendous promise for nano-electronics, photonics,
      catalysis, nano-sensors and electrochromic applications. In addition to graphene
      and metal dichalcogenides MX2 (M = Mo, W; X = S, Se, Te), 2D sub-stoichiometric
      WO(3-x) is gaining importance as a promising semiconductor material for field
      effect-transistor (FET) based devices. A combination of high permittivity,
      suppression of the Coulomb effects, and their stratified structure enhances the
      carrier mobility in such a material. Additionally, the sub-stoichiometry of this
      semiconductor oxide allows the reduction of the bandgap and increase of the free
      charge carriers at the same time. Here, we report for the first time H(+)
      intercalated WO(3) FETs, made of Q2D nano-flakes, with enhanced charge-carrier
      mobility exceeding 319 cm(2) V(-1) s(-1) comparable with the charge-carrier
      mobility of Q2D dichalcogenides MoS(2) and WSe(2). Analyses indicate that the
      enhanced electrical properties of the sub-stoichiometric WO(3-x) depend on the
      oxygen vacancies in the intercalated nano-flakes. These findings confirmed that
      Q2D sub-stoichiometric WO(3-x) is a promising material for various functional FET
      devices.

PMID- 25367430
TI  - The roles and regulation of Polycomb complexes in neural development.
AB  - In the developing mammalian nervous system, common progenitors integrate both
      cell extrinsic and intrinsic regulatory programs to produce distinct neuronal and
      glial cell types as development proceeds. This spatiotemporal restriction of
      neural progenitor differentiation is enforced, in part, by the dynamic
      reorganization of chromatin into repressive domains by Polycomb repressive
      complexes, effectively limiting the expression of fate-determining genes. Here,
      we review the distinct roles that Polycomb repressive complexes play during
      neurogenesis and gliogenesis, while also highlighting recent work describing the
      molecular mechanisms that govern their dynamic activity in neural development.
      Further investigation of the way in which Polycomb complexes are regulated in
      neural development will enable more precise manipulation of neural progenitor
      differentiation facilitating the efficient generation of specific neuronal and
      glial cell types for many biological applications. 

PMID- 25367434
TI  - Dependency of exercise-induced T-wave alternans predictive power for the
      occurrence of ventricular arrhythmias from heart rate.
AB  - BACKGROUND: T-wave alternans (TWA) is a noninvasive index of risk for the
      occurrence of ventricular arrhythmias. It is known that TWA amplitude (TWAA)
      increases with heart rate (HR) but how the TWA predictive power varies with HR
      remains unknown. Thus, the aim of this study was to evaluate the dependency of
      exercise-induced TWA predictive power for the occurrence of ventricular
      arrhythmias from HR. METHODS: TWA was identified using our HR adaptive match
      filter in exercise ECGs from 248 patients with implanted cardiac defibrillator
      (ICD), of which 72 developed ventricular tachycardia and/or fibrillation during
      the 4 year follow-up (ICD_Cases) and 176 did not (ICD_Controls). TWA predictive
      power was evaluated at HRs from 80 to 120 bpm by computing the area under the
      receiver operating characteristic curve (AUC) obtained using the maximum TWAA
      (maxTWAA) and the TWAA ratio (TWAAratio; i.e., the ratio between TWAA at a
      specific HR and at 80 bpm). RESULTS: TWAA increased with HR. At 80 bpm maxTWAA
      was lower than at 120 bpm in both ICD_Cases (22 MUV vs 41 MUV; P < 10(-2) ) and
      ICD_ Controls (16 MUV vs 36 MUV; P < 10(-4) ). However, only at 80 bpm ICD_Cases
      showed significantly higher maxTWAA than ICD_Controls (AUC = 0.6486; P = 0.0080).
      TWAAratio was higher in ICD_Controls than ICD_Cases for all HR but 120 bpm, and
      its predictive power was maximum at 115 bpm (AUC = 0.6914; P < 0.05).
      CONCLUSIONS: Exercise-induced TWA predictive power for the occurrence of
      ventricular arrhythmias, quantified using both maxTWAA and TWAAratio, was higher
      at low rather than at high HR.

PMID- 25367433
TI  - Next generation sequencing unravels the biosynthetic ability of spearmint (Mentha
      spicata) peltate glandular trichomes through comparative transcriptomics.
AB  - BACKGROUND: Plant glandular trichomes are chemical factories with specialized
      metabolic capabilities to produce diverse compounds. Aromatic mint plants produce
      valuable essential oil in specialised glandular trichomes known as peltate
      glandular trichomes (PGT). Here, we performed next generation transcriptome
      sequencing of different tissues of Mentha spicata (spearmint) to identify
      differentially expressed transcripts specific to PGT. Our results provide a
      comprehensive overview of PGT's dynamic metabolic activities which will help
      towards pathway engineering. RESULTS: Spearmint RNAs from 3 different tissues:
      PGT, leaf and leaf stripped of PGTs (leaf-PGT) were sequenced by Illumina paired
      end sequencing. The sequences were assembled de novo into 40,587 non-redundant
      unigenes; spanning a total of 101 Mb. Functions could be assigned to 27,025 (67%)
      unigenes and among these 3,919 unigenes were differentially expressed in PGT
      relative to leaf - PGT. Lack of photosynthetic transcripts in PGT transcriptome
      indicated the high levels of purity of isolated PGT, as mint PGT are non
      photosynthetic. A significant number of these unigenes remained unannotated or
      encoded hypothetical proteins. We found 16 terpene synthases (TPS), 18 cytochrome
      P450s, 5 lipid transfer proteins and several transcription factors that were
      preferentially expressed in PGT. Among the 16 TPSs, two were characterized
      biochemically and found to be sesquiterpene synthases. CONCLUSIONS: The extensive
      transcriptome data set renders a complete description of genes differentially
      expressed in spearmint PGT. This will facilitate the metabolic engineering of
      mint terpene pathway to increase yield and also enable the development of
      strategies for sustainable production of novel or altered valuable compounds in
      mint.

PMID- 25367435
TI  - Regular physical activity is associated with improved small artery distensibility
      in young to middle-age stage 1 hypertensives.
AB  - The aim of the present study was to investigate the association of physical
      activity with small artery elasticity in the early stage of hypertension. We
      examined 366 young-to-middle-age stage 1 hypertensives (mean blood pressure
      145.6+/-10.3/92.5+/-5.8 mmHg), divided into two categories of physical activity,
      sedentary (n=264) and non-sedentary (n=102) subjects. The augmentation index was
      measured using the Specaway DAT System. Small artery compliance (C2) was measured
      by applanation tonometry, at the radial artery, with an HDI CR2000 device. After
      6 years of follow-up, arterial distensibility assessment was repeated in 151
      subjects. Heart rate was lower in active than in sedentary subjects (71.2+/-8.9
      vs 76.6+/-9.7 bpm, p<0.001). After adjusting for age, sex, heart rate, smoking,
      and blood pressure, C2 was higher (8.0+/-2.6 vs 6.4+/-3.0 ml/mmHg * 100, p=0.008)
      in non-sedentary than in sedentary patients. The augmentation index was smaller
      in the former (8.8+/-20.1 vs 16.8+/-26.5%, p=0.044) but the difference lost
      statistical significance after further adjustment for blood pressure. After 6
      years, C2 was still higher in the non-sedentary than sedentary subjects. In
      addition, an improvement in the augmentation index accompanied by a decline in
      total peripheral resistance was found in the former. These data show that regular
      physical activity is associated with improved small artery elasticity in the
      early phase of hypertension. This association persists over time and is
      independent of blood pressure and heart rate. 

PMID- 25367436
TI  - Simple vs complex congenital nasolacrimal duct obstructions: etiology, management
      and outcomes.
AB  - BACKGROUND: The aim of this study was to report the comparative clinical profiles
      and outcomes of simple and complex congenital nasolacrimal duct obstruction
      (CNLDO). METHODS: The study was a retrospective chart review of all patients
      presenting with CNLDO from a single surgeon's (M.J.A.) database. All patients
      underwent irrigation and probing under nasal endoscopic guidance. A detailed
      lacrimal system evaluation was performed, intraoperative findings including nasal
      endoscopy were documented, and etiologies of complex CNLDO were noted. Outcome
      measures were comparative profiles, and anatomical success and functional success
      of the interventions. Statistical analyses were performed using the Shapiro-Wilk
      test, Fisher's exact test, and Wilcoxon rank sum test. RESULTS: Ninety-five eyes
      of 81 patients with simple CNLDO and 100 eyes of 83 patients with complex CNLDO
      were compared. The mean age at presentation was 17.6 months in simple CNLDO and
      45.6 months in complex cases (p < 0.001). Epiphora and discharge were the most
      common symptoms; 89.4% among simple cases and 92% in the complex group. The most
      common causes of complex CNLDO were bony obstructions (23%), craniofacial
      syndromes (12%), and buried probe (10%). At a mean follow-up of 5.85 months for
      simple CNLDO and 4.68 months for complex CNLDO, anatomical success and functional
      success was noted in 97.8% and 94.7%, respectively, in simple CNLDO, and in 58%
      and 51%, respectively, in complex CNDLO (p < 0.001). CONCLUSION: Bony
      obstruction, craniofacial syndrome, and buried probe were the most common reasons
      for a complex CNLDO, noted commonly in older children, with irrigation and
      probing having much poorer outcomes when compared with simpler obstructions.

PMID- 25367437
TI  - Conflict acts as an implicit cost in reinforcement learning.
AB  - Conflict has been proposed to act as a cost in action selection, implying a
      general function of medio-frontal cortex in the adaptation to aversive events.
      Here we investigate if response conflict acts as a cost during reinforcement
      learning by modulating experienced reward values in cortical and striatal
      systems. Electroencephalography recordings show that conflict diminishes the
      relationship between reward-related frontal theta power and cue preference yet it
      enhances the relationship between punishment and cue avoidance. Individual
      differences in the cost of conflict on reward versus punishment sensitivity are
      also related to a genetic polymorphism associated with striatal D1 versus D2
      pathway balance (DARPP-32). We manipulate these patterns with the D2 agent
      cabergoline, which induces a strong bias to amplify the aversive value of
      punishment outcomes following conflict. Collectively, these findings demonstrate
      that interactive cortico-striatal systems implicitly modulate experienced reward
      and punishment values as a function of conflict. 

PMID- 25367438
TI  - Three cases of bullous morphea: histopathologic findings with implications
      regarding pathogenesis.
AB  - Bullous morphea is a rare variant and is not frequently reported. We present
      three cases of bullous morphea. Although lymphangiectases have been suggested as
      the most likely mechanism for the development of the bullae in cases of morphea,
      none of the cases presented with lymphangiectases. To the contrary, all of our
      cases showed hemorrhagic content in the bullae, which suggests local trauma as a
      mechanism involved in bulla formation. 

PMID- 25367439
TI  - Effects of elevated temperature postharvest on color aspect, physiochemical
      characteristics, and aroma components of pineapple fruits.
AB  - In this work, 2 separate experiments were performed to describe the influence of
      elevated temperature treatments postharvest on the color, physiochemical
      characteristics and aroma components of pineapple fruits during low-temperature
      seasons. The L* (lightness) values of the skin and pulp of pineapple fruits were
      decreased. The a* (greenness-redness) and b* (blueness-yellowness) values of the
      skin and pulp were all markedly increased. The elevated temperature significantly
      increased the contents of total soluble solids (TSS) and slightly affected
      contents of vitamin C (nonsignificant). Titratable acidity (TA) of pineapple
      fruits were notably decreased, whereas the values of TSS/TA of pineapple fruits
      were significantly increased. The firmness of the pineapple fruits decreased and
      more esters and alkenes were identified. The total relative contents of esters
      were increased, and the total relative contents of alkenes were decreased. 

PMID- 25367440
TI  - Conversion of hemi into reverse shoulder arthroplasty: implant design
      limitations.
AB  - PURPOSE: Cranial migration of shoulder hemiarthroplasties due to rotator cuff
      insufficiency typically requires conversion into a reverse total shoulder
      arthroplasty. This study was conducted to analyze differences between the height
      and offset of six implants designed to enable conversion of a hemiarthroplasty
      into a reverse system. METHODS: Anteroposterior radiographs of 40 shoulders were
      taken. An image analyzing software was used to simulate the implantation of the
      hemiprostheses. Then the implant was dissembled, leaving on the stem within the
      humeral shaft. Finally, the implantation of a reverse system was simulated using
      the stem in the same position. Values are reported as ?-height and ?-offset +/-
      standard deviation. Significance was assumed for P < 0.05. RESULTS: The least
      decrease in height was determined for Implantcast with 11.6 +/- 3.3 mm, followed
      by DePuy (16 +/- 5.7 mm) and the greatest for Tornier with 33 +/- 5.3 mm. No
      significant differences were found among Exactech, Mathys and Zimmer. The largest
      offset-deviation was calculated for DePuy (-21.7 +/- 3.7 mm) and the smallest for
      Implantcast (-3.3 +/- 2.8 mm) and Tornier (1.5 +/- 5.7 mm). CONCLUSIONS: Due to
      the modular stem, the system of Implantcast can be converted in a reverse system
      with the least changes in height and offset. For the other manufacturers it does
      not seem possible to convert a hemiprosthesis to a reversed prosthesis without
      accepting additional tension of the deltoid muscle. Further experimental studies
      have to analyze the changes in deltoid abduction moments after conversion of a
      hemi- into a reversed prosthesis.

PMID- 25367441
TI  - Lipoteichoic acid challenge induces higher inflammatory responses than
      lipopolysaccharide in UV-irradiated keratinocytes.

PMID- 25367442
TI  - The influence of personality and coping on female sexual function: a population
      survey.
AB  - INTRODUCTION: Female sexual dysfunction (FSD) is a common disorder with limited
      data investigating relationships with psychological influences, such as
      personality traits and coping mechanisms. AIM: To investigate the relationship
      and impact of personality traits and coping strategies on female sexual function.
      METHODS: A web-based survey was distributed to a sample of women representative
      of the area's demographic distribution. MAIN OUTCOME MEASURES: Participants
      completed the Female Sexual Function Index (FSFI), the Ten Item Personality Index
      (TIPI), and the Brief COPE. RESULTS: Five hundred twenty-six females responded.
      The mean total FSFI score was 24.56 (SD 6.77) with lowest scores in the desire
      domain. Personality scores were similar to published normative values. Subjects
      displaying stronger tendencies for introversion (r = 0.246, P < 0.001), not being
      open to new experiences (r = 0.159, P = 0.008), and emotional instability (r =
      0.244, P < 0.001) were found to have significantly worse sexual function.
      Conscientiousness was significantly associated with better desire, orgasm,
      satisfaction, and total FSFI score (P = 0.029, P = 0.002, P = 0.005, P = 0.003).
      Moreover, the utilization of negative coping strategies such as self-blame, self
      distraction, and behavioral disengagement, significantly correlated with poor
      sexual function (r = -0.298, P < 0.001, r = -0.360, P < 0.001, r = -0.398, P <
      0.001, respectively). CONCLUSION: Personality and coping are linked to sexual
      function with introversion, not being open to new experiences, emotional
      instability, and the utilization of negative coping strategies being
      significantly associated with poor sexual function. Women presenting with sexual
      function complaints may need further evaluation of their personality and coping
      strategies in order to mitigate any negative impact of these tendencies.

PMID- 25367443
TI  - Isolated pentagon rule violating endohedral metallofullerenes explained using the
      Huckel rule: a statistical mechanical study of the C84 Isomeric Set.
AB  - Fullerenes and their structure and stability have been a major topic of
      discussion and research since their discovery nearly 30 years ago. The isolated
      pentagon rule (IPR) has long served as a guideline for predicting the most stable
      fullerene cages. More recently, endohedral metallofullerenes have been discovered
      that violate the IPR. This article presents a systematic, temperature dependent,
      statistical thermodynamic study of the 24 possible IPR isomers of C84 as well as
      two of the experimentally known non-IPR isomers (51365 and 51383), at several
      different charges (0, -2, -4, and -6). From the results of this study, we
      conclude that the Huckel rule is a valid simpler explanation for the stability of
      fused pentagons in endohedral metallofullerenes.

PMID- 25367444
TI  - The hookup: collaborative evaluation of a youth sexual health program using text
      messaging technology.
AB  - BACKGROUND: The Hookup is a collaborative project reaching young people in
      California with valuable sexual and reproductive health information and linkage
      to local resources. Due to limited access to subscriber contact information, it
      has been a challenge to evaluate the program. OBJECTIVE: The aims of this study
      were to determine the feasibility of using text messaging (short message service,
      SMS) as an evaluation tool for an educational text message-based program and to
      evaluate the program itself. METHODS: All subscribers of The Hookup were sent
      four survey questions via SMS about age, gender, location, referral source and
      behavior change. An incentive was offered for completing the survey and an opt
      out option was provided in the initial message. RESULTS: All existing subscribers
      of The Hookup (N=2477) received a request to complete the survey using the SMS
      application on their mobile phones. A total of 832 (33.6%) subscribers responded
      to the initial question and 481 (20%) answered all four questions. Of the
      responses, 85% were received in the first two hours of the initial request.
      Respondents who answered the question about behavior change, 90% reported having
      made some positive change since subscribing to Hookup, including getting tested
      for STDs and HIV. CONCLUSIONS: The survey methodology initiated a high response
      rate from The Hookup subscribers. The survey was able to provide data about
      subscribers in a short time period at minimal cost. The results show potential
      for using mobile SMS applications to evaluate SMS campaigns. The findings also
      support using SMS to provide young people with sexual health prevention messaging
      and linkage to health services.

PMID- 25367445
TI  - Tendon to bone tunnel healing--a study on the time-dependent changes in
      biomechanics, bone remodeling, and histology in a rat model.
AB  - Tendons and ligaments attach to bone through a transitional connective tissue
      with complex biomechanical properties. This unique tissue is not regenerated
      during healing, and surgical reattachment therefore often fails. The present
      study was designed to evaluate tendon healing in a bone tunnel and to evaluate
      the utilized rat model. Wistar rats (n = 61) were operated with the Achilles
      tendon through a bone tunnel in the distal tibia. Healing was evaluated at 2, 3,
      4, and 12 weeks by biomechanical testing, bone mineral density and histology.
      After 2 weeks median (interquartile range) pull-out force was 2.2 N (1.9). The
      pull-out force increased chronologically, by 12 weeks fivefold to 11.2 N (11.4).
      Energy absorption, stiffness, and bone mineral density increased similarly. The
      histological analyses showed inflammation at early stages with increasing callus
      by time. Our data showed a slow healing response the first 4 weeks followed by an
      accelerated healing period, favoring that most of the gain in mechanical strength
      occurred later than 4 weeks postoperatively. These findings support the concern
      of a vulnerable tendon bone tunnel interface in the early stages of healing.

PMID- 25367446
TI  - The first one-pot synthesis of metal-organic frameworks functionalised with two
      transition-metal complexes.
AB  - The synthesis of a metal-organic framework (UiO-67) functionalised simultaneously
      with two different transition metal complexes (Ir and Pd or Rh) through a one-pot
      procedure is reported for the first time. This has been achieved by an iterative
      modification of the synthesis parameters combined with characterisation of the
      resulting materials using different techniques, including X-ray absorption
      spectroscopy (XAS). The method also allows the first synthesis of UiO-67 with a
      very wide range of loadings (from 4 to 43 mol %) of an iridium complex
      ([IrCp*(bpydc)(Cl)Cl](2-) ; bpydc=2,2'-bipyridine-5,5'-dicarboxylate,
      Cp*=pentamethylcyclopentadienyl) through a pre-functionalisation methodology. 

PMID- 25367447
TI  - Enhancement of visible photocatalytic performances of a Bi2MoO6-BiOCl
      nanocomposite with plate-on-plate heterojunction structure.
AB  - A visible-light-sensitive Bi2MoO6-BiOCl heterojunction photocatalyst was
      synthesized via a hydrothermal process. The as-prepared Bi2MoO6-BiOCl composite
      shows an irregular multi-plate structure with length ranging from 100 nm to 1
      MUm, indicating a possibility of the plate-on-plate structure by placing Bi2MoO6
      and BiOCl nanoplates over each other. The Bi2MoO6-BiOCl photocatalyst not only
      had a good visible-light photocatalytic performance, but also exhibited higher
      photocatalytic activity than pure BiOCl and Bi2MoO6. The optimal Bi2MoO6 content
      for the photocatalytic activity of the Bi2MoO6-BiOCl composites is 30%. Compared
      to pure Bi2MoO6 the photoactivity of the Bi2MoO6-BiOCl composites is almost 2.0
      times higher for the RhB photodegradation, and 1.5 times higher for the phenol
      photodegradation under visible light irradiation. The photocatalytic mechanism
      was elucidated via active species trapping experiments and ESR. The OH and O2(-)
      played the key roles in the degradation of RhB via the Bi2MoO6-BiOCl composite.
      Finally, the possible charge transfer mechanism of the enhanced visible light
      photocatalytic activity was proposed. 

PMID- 25367450
TI  - Highly abnormal SPECT in a patient with left ventricular non-compaction and no
      evidence of obstructive coronary artery disease.

PMID- 25367448
TI  - FTO rs9939609 polymorphism is associated with metabolic disturbances and response
      to HCV therapy in HIV/HCV-coinfected patients.
AB  - BACKGROUND: The Fat Mass and Obesity-Associated Protein (FTO) gene rs9939609
      single nucleotide polymorphism (SNP) has been associated with obesity, metabolic
      syndrome, insulin resistance (IR), and type 2 diabetes mellitus in the general
      population. The aim of our study was to examine for the first time the
      association of the rs9939609 polymorphism with metabolic disturbances, liver
      disease and virologic response to hepatitis C virus (HCV) therapy with pegylated
      interferon-alpha plus ribavirin (pegIFNalpha/RBV) in human immunodeficiency virus
      (HIV)/HCV coinfected patients. METHODS: We carried out a cross-sectional study in
      261 patients, of whom 178 were subsequently treated with pegIFNalpha/RBV therapy.
      FTO rs9939609 and IFNL3 rs12980275 polymorphisms were genotyped by GoldenGate(r).
      The main outcomes were: 1) metabolic disturbances: insulin resistance
      (homeostatic model assessment (HOMA-IR)) and overweight (body mass index (BMI));
      2) liver disease (Metavir score): significant fibrosis (F >=2) and steatosis
      (>10% fatty hepatocytes); and 3) virologic response to HCV treatment: sustained
      virologic response (SVR). RESULTS: The rs9939609 AA genotype was associated with
      higher values of BMI (adjusted arithmetic mean ratio (aAMR) = 1.08; 95%
      confidence interval (95%CI) = 1.03 to 1.14; P = 0.002) and HOMA-IR (aAMR = 1.32;
      95%CI = 1.03 to 1.69; P = 0.027). Patients with an rs9939609 AA genotype had
      higher likelihoods of achieving values of BMI >=27.5 kg/m2 (adjusted odds ratio
      (aOR) = 3.46; 95%CI =1.17 to 10.21; P = 0.024), HOMA-IR >=2.5 (aOR = 2.09; 95%CI
      = 1.02 to 4.32; P = 0.045), significant fibrosis (aOR = 2.34; 95%CI =1.02 to
      5.36; P = 0.045) and steatosis (aOR = 3.65; 95%CI = 1.29 to 10.36; P = 0.015).
      The rs9939609 AT/AA genotype decreased the likelihood of achieving SVR (aOR =
      0.58; 95%CI = 0.34 to 0.99; P = 0.044). A decision tree was performed with the
      genotypes of HCV, IFNL3 and FTO. The incorporation of rs9939609 significantly
      improves the prediction of SVR (P <0.05). The overall accuracy was 68.2%.
      CONCLUSIONS: Patients carrying the unfavourable AT/AA genotype of rs9939609
      polymorphism had higher odds of metabolic disturbances and a lower likelihood of
      achieving successful virologic response to HCV therapy.

PMID- 25367451
TI  - Acute left ventricular dys-synchrony during regadenason PET myocardial perfusion
      stress test.

PMID- 25367452
TI  - Evaluation of image reconstruction algorithms encompassing Time-Of-Flight and
      Point Spread Function modelling for quantitative cardiac PET: phantom studies.
AB  - BACKGROUND: To perform kinetic modelling quantification, PET dynamic data must be
      acquired in short frames, where different critical conditions are met. The
      accuracy of reconstructed images influences quantification. The added value of
      Time-Of-Flight (TOF) and Point Spread Function (PSF) in cardiac image
      reconstruction was assessed. METHODS: A static phantom was used to simulate two
      extreme conditions: (i) the bolus passage and (ii) the steady uptake. Various
      count statistics and independent noise realisations were considered. A moving
      phantom filled with two different radionuclides was used to simulate: (i) a great
      range of contrasts and (ii) the cardio/respiratory motion. Analytical and
      iterative reconstruction (IR) algorithms also encompassing TOF and PSF modelling
      were evaluated. RESULTS: Both analytic and IR algorithms provided good results in
      all the evaluated conditions. The amount of bias introduced by IR was found to be
      limited. TOF allowed faster convergence and lower noise levels. PSF achieved near
      full myocardial activity recovery in static conditions. Motion degraded
      performances, but the addition of both TOF and PSF maintained the best overall
      behaviour. CONCLUSIONS: IR accounting for TOF and PSF can be recommended for the
      quantification of dynamic cardiac PET studies as they improve the results
      compared to analytic and standard IR.

PMID- 25367453
TI  - Imaging cardiac amyloidosis: an opportunity for nuclear cardiology.

PMID- 25367454
TI  - Incidentally found giant thymomas by SPECT myocardial perfusion imaging.

PMID- 25367455
TI  - Phenolic glycosides from Glycosmis pentaphylla.
AB  - Three new phenolic glycosides, named as glycopentosides A-C (1-3), along with
      nine known compounds were isolated from the n-BuOH extract of stems of Glycosmis
      pentaphylla. Their structures were determined by using spectroscopic and chemical
      methods. Bioassay showed that compound 10 (tachioside) could inhibit nitric oxide
      production in lipopolysaccharides-stimulated RAW 264.7 cells with IC50 value of
      12.14 MUM.

PMID- 25367456
TI  - Coagulase-negative Staphylococcus culture in chronic rhinosinusitis.
AB  - BACKGROUND: Coagulase-negative Staphylococcus (CoNS) is commonly isolated from
      patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS
      remains controversial. We aimed to determine the association between positive
      CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity.
      METHODS: Adult CRS patients who underwent FESS between October 1, 2007 to
      December 31, 2011 were recruited. Patient demographics, disease characteristics,
      medication use, Lund-Mackay computed tomography (CT) scores, and 22-item Sino
      Nasal Outcome Test (SNOT-22) scores were collected at baseline before FESS.
      Intraoperative cultures were obtained in a standard manner. Patients were placed
      into 2 groups based on culture findings: patients with CoNS as the sole positive
      culture result and patients with all other positive culture results, including
      CoNS, as part of a polymicrobial culture. RESULTS: A total of 376 CRS patients
      met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%)
      had other positive cultures, and 10 (3%) had no bacterial growth. Compared to
      patients with other positive cultures, patients with the sole result of CoNS were
      significantly less likely to have a history of FESS (52% vs 65%, p = 0.019),
      nasal polyps (50% vs 65%, p = 0.006), and had a better Lund-Mackay CT score
      (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple
      logistic regression model, CoNS as the sole positive culture result was
      independently associated with having no history of FESS (odds ratio [OR] = 0.45;
      95% confidence interval [CI], 0.22 to 0.94; p = 0.034). CONCLUSION: Positive
      intraoperative CoNS cultures alone do not result in increased CRS disease burden
      by objective or subjective measures as compared to patients with other bacterial
      or polymicrobial culture isolates.

PMID- 25367457
TI  - Reduced body mass index in essential tremor: a study of 382 cases and 392 matched
      controls.
AB  - BACKGROUND AND PURPOSE: There is mounting evidence that essential tremor (ET) is
      a neurodegenerative disease. Reduced body mass index (BMI) is a clinical feature
      of many neurodegenerative diseases, yet there has been little documentation of
      BMI in patients with ET. METHODS: Essential tremor cases and controls were
      enrolled in a study of the environmental epidemiology of ET at Columbia
      University Medical Center. Weight and height were measured using a standard
      protocol; BMI was weight (kg) divided by height (m(2)). Daily calorie count
      (kcal) was calculated using the Willett Semi-Quantitative Food Frequency
      Questionnaire. Tremor severity was assessed with a clinical rating scale (total
      tremor score, range 0-36). RESULTS: The 382 ET cases and 392 controls were
      similar with respect to age, gender and other demographic variables. BMI was
      lower in ET cases than controls [26.7 +/- 5.0 (median = 26.2) vs. 27.7 +/- 5.6
      (median = 26.7), P = 0.03] despite the fact that the daily caloric intake was
      marginally higher in ET cases than controls (P = 0.09). In ET cases, BMI was not
      associated with tremor severity (Spearman's r = -0.02, P = 0.66) but, among
      younger onset ET cases, longer tremor duration was associated with lower BMI
      (Spearman's r = -0.14, P = 0.049). CONCLUSIONS: The observed lower BMI in ET is
      consistent with the neurodegenerative hypothesis of ET. The data also suggest
      that some mechanism other than decreased daily caloric intake or an involuntary
      movement-related increased burning of calories is likely to account for this case
      control difference.

PMID- 25367459
TI  - Bioactive composition, antimicrobial activities and the influence of Agrocybe
      aegerita (Brig.) Sing on certain quorum-sensing-regulated functions and biofilm
      formation by Pseudomonas aeruginosa.
AB  - Agrocybe aegerita (Brig.) Sing is a basidiomycete, white rot fungus.
      Antimicrobial activities and the antiqourum effect on Pseudomonas aeruginosa of
      an A. aegerita methanolic extract were investigated. The extract showed very good
      antimicrobial activity against all the tested microorganisms in a dose dependent
      manner. Effects of the Sub-MIC, MIC and 2MIC of the A. aegerita methanolic
      extract regulated the virulence factors in the quorum sensing (QS) test, as well
      as biofilm formation on P. aeruginosa. Sub-inhibitory and inhibitory
      concentrations of the extract demonstrated the reduction of virulence factors
      such as pyocyanin production, twitching and swimming motility. The biofilm
      forming capability of P. aeruginosa PAO1 was also reduced in a concentration
      dependent manner. Furthermore, the chemical composition of the methanolic extract
      was determined considering its phenolic composition. The methanolic extract of A.
      aegerita can be a very good source of bioactive substances. This research is of
      great importance due to the prevalence of drug-resistant microorganisms. 

PMID- 25367458
TI  - The time has come to test the beta cell preserving effects of exercise in
      patients with new onset type 1 diabetes.
AB  - Type 1 diabetes is characterised by immune-mediated destruction of insulin
      producing beta cells. Significant beta cell function is usually present at the
      time of diagnosis with type 1 diabetes, and preservation of this function has
      important clinical benefits. The last 30 years have seen a number of largely
      unsuccessful trials for beta cell preservation, some of which have been of
      therapies that have potential for significant harm. There is a need to explore
      new, more tolerable approaches to preserving beta cell function that can be
      implemented on a large clinical scale. Here we review the evidence for physical
      exercise as a therapy for the preservation of beta cell function in patients with
      newly diagnosed type 1 diabetes. We highlight possible mechanisms by which
      exercise could preserve beta cell function and then present evidence from other
      models of diabetes that demonstrate that exercise preserves beta cell function.
      We conclude by proposing that there is now a need for studies to explore whether
      exercise can preserve beta cell in patients newly diagnosed with type 1 diabetes.

PMID- 25367460
TI  - Hepatocyte growth factor deficiency in COPD: a mechanism of emphysema and small
      airway fibrosis?

PMID- 25367461
TI  - Primary ciliary dyskinesia and the heart: cilia breaking symmetry.

PMID- 25367462
TI  - Atrial fibrillation during sepsis: a determinant of long-term outcomes?

PMID- 25367463
TI  - Fibroproliferative ARDS in the Era of low-tidal-volume ventilation.

PMID- 25367464
TI  - POINT: are there cases in which physicians should deviate from recommendations
      not to order a chest CT scan? Yes.

PMID- 25367465
TI  - Counterpoint: are there cases in which physicians should deviate from
      recommendations not to order a chest CT scan? No.

PMID- 25367466
TI  - Rebuttal from Dr Halpern.

PMID- 25367467
TI  - Rebuttal from Dr Simpson.

PMID- 25367468
TI  - Giants in chest medicine: Richard W. Light, MD.

PMID- 25367469
TI  - Arterial lines in the ICU: a call for rigorous controlled trials.
AB  - The appropriate justification for using a diagnostic or therapeutic intervention
      is that it provides benefit to patients, society, or both. For decades,
      indwelling arterial catheters have been used very commonly in patients in the
      ICU, despite a complete absence of data addressing whether they confer any such
      benefits. Both of the main uses of arterial catheters, BP monitoring and blood
      sampling for laboratory testing, can be done without these invasive devices.
      Prominent among complications of arterial catheters are bloodstream infections
      and arterial thrombosis. To my knowledge, only a single observational study has
      assessed a patient-centered outcome related to arterial catheter use, and it
      found no evidence that they reduce hospital mortality in any patient subgroup.
      Given the potential dangers, widespread use, and uncertainty about consequences
      of arterial catheter use in ICUs, equipoise exists and randomized trials are
      needed. Multiple studies in different, well-characterized, patient subgroups are
      needed to clarify whether arterial catheters influence outcomes. These studies
      should assess the range of relevant outcomes, including mortality, medical
      resource use, patient comfort, complications, and costs. 

PMID- 25367470
TI  - Distinct characteristics of pleuroparenchymal fibroelastosis with usual
      interstitial pneumonia compared with idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare form of
      interstitial pneumonia and sometimes coexists with a histologic usual
      interstitial pneumonia (UIP) pattern. This study aimed to describe the distinct
      clinical features of PPFE with UIP pattern compared with idiopathic pulmonary
      fibrosis (IPF). METHODS: We conducted a retrospective review of the medical
      records of 110 consecutive patients with IPF with a histologic UIP pattern on
      surgical lung biopsy specimen. Patients meeting radiologic criteria for the
      diagnosis of PPFE based on high-resolution CT scan and with a histologic UIP
      pattern were included. RESULTS: Nine of eleven patients meeting radiologic
      criteria for the diagnosis of PPFE were histologically confirmed as having PPFE
      with UIP pattern. The PPFE with UIP pattern group showed a significantly higher
      residual volume (1.8 L vs 1.3 L, P < .01), higher Paco2 (44.6 mm Hg vs 41.7 mm
      Hg, P = .04), and higher complication rate of pneumothorax and pneumomediastinum
      than the 99 patients with IPF/UIP. The ratio of anteroposterior to transthoracic
      diameter in patients with PPFE with UIP pattern was significantly lower than that
      in patients with IPF/UIP (P = .04). Survival time tended to be shorter in
      patients with PPFE with UIP pattern. CONCLUSIONS: The results support the view
      that PPFE with UIP pattern is a disease entity distinct from IPF/UIP and may well
      be classified as PPFE.

PMID- 25367471
TI  - Scientific foundations of allergen-specific immunotherapy for allergic disease.
AB  - Allergen-specific immunotherapy (AIT) was described as a therapeutic option for
      the treatment of allergies > 100 years ago. It is based on administration of
      allergen extracts and leads to the development of clinical allergen tolerance in
      selected patients. According to current knowledge, AIT results in the restoration
      of immune tolerance toward the allergen of interest. It is mainly accompanied by
      the induction of regulatory and suppressive subsets of T and B cells, the
      production of IgG4 isotype allergen-specific blocking antibodies, and decreased
      inflammatory responses to allergens by effector cells in inflamed tissues.
      Currently, AIT is mainly applied subcutaneously or sublingually and is suitable
      for both children and adults for pollen, pet dander, house dust mite, and venom
      allergies. It not only affects rhinoconjunctival symptoms but also has documented
      short- and long-term benefits in asthma treatment. Clinically, a fast onset of
      tolerance is achieved during desensitization, with a tolerable amount of side
      effects. The disease modification effect leads to decreased disease severity,
      less drug usage, prevention of future allergen sensitizations, and a long-term
      curative effect. Increasing safety while maintaining or even augmenting
      efficiency is the main goal of research for novel vaccine development and
      improvement of treatment schemes in AIT. This article reviews the principles of
      allergen-specific immune tolerance development and the effects of AIT in the
      clinical context. 

PMID- 25367472
TI  - Diagnosis and treatment of pulmonary aspergillosis syndromes.
AB  - Both inherited and acquired immunodeficiency and chronic pulmonary disease
      predispose to the development of a variety of pulmonary syndromes in response to
      Aspergillus, a fungus that is ubiquitous in the environment. These syndromes
      include invasive aspergillosis, which is now recognized to occur in patients with
      critical illness without neutropenia and in those with mild degrees of
      immunosuppression, including from corticosteroid use in the setting of COPD.
      Chronic pulmonary aspergillosis includes simple aspergilloma, which is
      occasionally complicated by life-threatening hemoptysis, and progressive
      destructive cavitary disease requiring antifungal therapy. Allergic
      bronchopulmonary aspergillosis occurs almost exclusively in patients with asthma
      or cystic fibrosis. Recent advances in each of these syndromes include a greater
      understanding of the underlying pathophysiology and hosts at risk; improved
      diagnostic algorithms; and the availability of more effective and well-tolerated
      therapies. Improvement in outcomes for Aspergillus pulmonary syndromes requires
      that physicians recognize the varied and sometimes subtle presentations, be aware
      of populations at risk of illness, and institute potentially life-saving
      therapies early in the disease course. 

PMID- 25367473
TI  - Physician strikes.
AB  - Throughout medical history, physicians have rarely formed unions and/or carried
      out strikes. In a profession faced with the turmoil of health reform and
      increasing pressure to change their practices and lifestyles, will physicians
      resort to unionization for collective bargaining, and will a strike weapon be
      used to fight back against the array of corporate and government powers involved
      in the transformation of the American health-care system? This article examines
      the question of whether there could be such a thing as an ethical physician
      strike. Although physicians have not historically used collective bargaining or
      the strike weapon, the rapidly changing practice environment in the United States
      might push physicians and other health-care professionals toward unionization.
      This article considers the ethical questions that would arise if physicians
      started taking advantage of labor laws, and it lays out criteria for an ethical
      strike. 

PMID- 25367474
TI  - Contemporary approach to neurologic prognostication of coma after cardiac arrest.
AB  - Coma after cardiac arrest (CA) is an important cause of admission to the ICU.
      Prognosis of post-CA coma has significantly improved over the past decade,
      particularly because of aggressive postresuscitation care and the use of
      therapeutic targeted temperature management (TTM). TTM and sedatives used to
      maintain controlled cooling might delay neurologic reflexes and reduce the
      accuracy of clinical examination. In the early ICU phase, patients' good recovery
      may often be indistinguishable (based on neurologic examination alone) from
      patients who eventually will have a poor prognosis. Prognostication of post-CA
      coma, therefore, has evolved toward a multimodal approach that combines
      neurologic examination with EEG and evoked potentials. Blood biomarkers (eg,
      neuron-specific enolase [NSE] and soluble 100-beta protein) are useful
      complements for coma prognostication; however, results vary among commercial
      laboratory assays, and applying one single cutoff level (eg, > 33 MUg/L for NSE)
      for poor prognostication is not recommended. Neuroimaging, mainly diffusion MRI,
      is emerging as a promising tool for prognostication, but its precise role needs
      further study before it can be widely used. This multimodal approach might reduce
      false-positive rates of poor prognosis, thereby providing optimal prognostication
      of comatose CA survivors. The aim of this review is to summarize studies and the
      principal tools presently available for outcome prediction and to describe a
      practical approach to the multimodal prognostication of coma after CA, with a
      particular focus on neuromonitoring tools. We also propose an algorithm for the
      optimal use of such multimodal tools during the early ICU phase of post-CA coma. 

PMID- 25367475
TI  - International classification of sleep disorders-third edition: highlights and
      modifications.
AB  - The recently released third edition of the International Classification of Sleep
      Disorders (ICSD) is a fully revised version of the American Academy of Sleep
      Medicine's manual of sleep disorders nosology, published in cooperation with
      international sleep societies. It is the key reference work for the diagnosis of
      sleep disorders. The ICSD-3 is built on the same basic outline as the ICSD-2,
      identifying seven major categories that include insomnia disorders, sleep-related
      breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep
      wake disorders, sleep-related movement disorders, parasomnias, and other sleep
      disorders. Significant modifications have been made to the nosology of insomnia,
      narcolepsy, and parasomnias. Major features and changes of the manual are
      reviewed in this article. The rationales for these changes are also discussed. 

PMID- 25367476
TI  - Pulmonary effects and complications of snakebites.
AB  - This review is on the pulmonary complications of snakebites, which can have fatal
      consequences. We identified three common themes as reported in the literature
      regarding envenomation: generalized neuromuscular paralysis affecting airway and
      respiratory muscles, pulmonary edema, and pulmonary hemorrhages or thrombosis due
      to coagulopathy. Respiratory paralysis and pulmonary edema can be due to either
      elapid or viper bites, whereas pulmonary complications of coagulopathy are
      exclusively reported with viper bites. The evidence for each complication,
      timeline of appearance, response to treatment, and details of pathophysiology are
      discussed. 

PMID- 25367477
TI  - The resource-based relative value scale and physician reimbursement policy.
AB  - Most physicians are unfamiliar with the details of the Resource-Based Relative
      Value Scale (RBRVS) and how changes in the RBRVS influence Medicare and private
      reimbursement rates. Physicians in a wide variety of settings may benefit from
      understanding the RBRVS, including physicians who are employees, because many
      organizations use relative value units as productivity measures. Despite the
      complexity of the RBRVS, its logic and ideal are simple: In theory, the resource
      usage (comprising physician work, practice expense, and liability insurance
      premium costs) for one service is relative to the resource usage of all others.
      Ensuring relativity when new services are introduced or existing services are
      changed is, therefore, critical. Since the inception of the RBRVS, the American
      Medical Association's Relative Value Scale Update Committee (RUC) has made
      recommendations to the Centers for Medicare & Medicaid Services on changes to
      relative value units. The RUC's core focus is to develop estimates of physician
      work, but work estimates also partly determine practice expense payments. Critics
      have attributed various health-care system problems, including declining and
      growing gaps between primary care and specialist incomes, to the RUC's role in
      the RBRVS update process. There are persistent concerns regarding the quality of
      data used in the process and the potential for services to be overvalued. The
      Affordable Care Act addresses some of these concerns by increasing payments to
      primary care physicians, requiring reevaluation of the data underlying work
      relative value units, and reviewing misvalued codes. 

PMID- 25367480
TI  - Refractory hypoxemia in a 23-year-old patient with Budd-Chiari syndrome.
AB  - Antiphospholipid syndrome is an autoimmune disorder characterized by a
      hypercoagulable state, leading to arterial and venous thrombosis. We present a 23
      year-old patient, suspected of having Budd-Chiari syndrome due to
      antiphospholipid syndrome, who developed severe and progressive hypoxemia,
      requiring prolonged mechanical ventilation. After a detailed but unsuccessful
      workup, a contrast CT scan revealed an occluded superior vena cava and azygos
      vein-superior vena cava junction and massive right-to-left shunting through a
      network of systemic to pulmonary venous collaterals. Restoring normal blood flow
      from the azygos vein into the right atrium by stenting the azygos-superior vena
      cava junction resolved the hypoxemia immediately. Within the same procedure, the
      hepatic outflow obstruction was successfully treated by stenting a severe
      stenosis of the suprahepatic inferior vena cava caused by calcified thrombus. 

PMID- 25367481
TI  - Bilateral vocal cord paralysis requiring tracheostomy due to neuroborreliosis.
AB  - Neuroborreliosis can cause multiple cranial and peripheral neuropathies; however,
      involvement of both recurrent laryngeal nerves is rare. We report the case of a
      90-year-old man who presented with dysphonia and right upper and lower extremity
      weakness. His course was complicated by bilateral vocal cord paralysis and
      respiratory failure requiring tracheostomy. The diagnosis of borreliosis was made
      by detection of IgM and IgG antibodies against Borrelia burgdorferi on enzyme
      immunoassay and Western blot. The patient received IV ceftriaxone for 2 weeks,
      followed by complete recovery of motor and vocal function over 2 months. Our case
      is the third report of bilateral vocal cord paralysis in the literature, and the
      first one, to our knowledge, presenting with respiratory failure requiring an
      artificial airway. Physicians should be aware of this unusual complication of
      neuroborreliosis. 

PMID- 25367482
TI  - An elderly woman that presents with absent vital signs.

PMID- 25367483
TI  - A 70-year-old man with intraoperative hypoxia and hypotension during total hip
      replacement.
AB  - A 70-year-old man underwent total hip replacement surgery under general
      anesthesia, endotracheal intubation, and controlled ventilation, with the patient
      in left lateral position. Intraoperatively, the patient was hemodynamically
      stable, with a normal range of pulse, ECG trace, oxygen saturation as measured by
      pulse oximetry (Spo2), and end-tidal CO2 (etco2). Five minutes after insertion of
      the hip prosthesis, his heart rate dropped to 30 beats/min, BP to 40/30 mm Hg,
      Spo2 to 70%, and etco2 to 10 mm Hg. 

PMID- 25367484
TI  - A 54-year-old woman with postextubation stridor.

PMID- 25367485
TI  - Manifold embryonic ciliary functions in the genesis of kartagener syndrome and
      heterotaxy.

PMID- 25367486
TI  - Response.

PMID- 25367487
TI  - Are we correctly defining intermediate-risk pulmonary embolism?

PMID- 25367488
TI  - Response.

PMID- 25367489
TI  - Transthoracic needle biopsy for pleural and peripheral lung lesions:
      ultrasonography vs CT scan guidance.

PMID- 25367490
TI  - Response.

PMID- 25367491
TI  - Hemoptysis after cryoablation for atrial fibrillation: truth or just a myth?

PMID- 25367492
TI  - OSA among patients with pneumonia: a higher risk for complications or simply an
      overlapping disorder?

PMID- 25367493
TI  - Response.

PMID- 25367494
TI  - Advantages of thoracic ultrasound-guided fine-needle aspiration biopsy in lung
      cancer and mesothelioma.

PMID- 25367495
TI  - Response.

PMID- 25367496
TI  - Higher fluids in the first three hours of sepsis resuscitation? Too soon to
      conclude.

PMID- 25367497
TI  - Response.

PMID- 25367498
TI  - Cricoarytenoid subluxation: another cause of pseudoasthma.

PMID- 25367499
TI  - Duration of symptoms prior to antibiotic use, and length of stay in infected
      patients.

PMID- 25367500
TI  - Biocompatible conjugated polymer nanoparticles for efficient photothermal tumor
      therapy.
AB  - Conjugated polymers (CPs) with strong near-infrared (NIR) absorption and high
      heat conversion efficiency have emerged as a new generation of photothermal
      therapy (PTT) agents for cancer therapy. An efficient strategy to design NIR
      absorbing CPs with good water dispersibility is essential to achieve excellent
      therapeutic effect. In this work, poly[9,9-bis(4-(2-ethylhexyl)phenyl)fluorene
      alt-co-6,7-bis(4-(hexyloxy)phenyl)-4,9-di(thiophen-2-yl)-thiadiazoloquinoxaline]
      (PFTTQ) is synthesized through the combination of donor-acceptor moieties by
      Suzuki polymerization. PFTTQ nanoparticles (NPs) are fabricated through a
      precipitation approach using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N
      [methoxy(polyethylene glycol)-2000] (DSPE-PEG2000 ) as the encapsulation matrix.
      Due to the large NIR absorption coefficient (3.6 L g(-1) cm(-1) ), the
      temperature of PFTTQ NP suspension (0.5 mg/mL) could be rapidly increased to more
      than 50  degrees C upon continuous 808 nm laser irradiation (0.75 W/cm(2) ) for 5
      min. The PFTTQ NPs show good biocompatibility to both MDA-MB-231 cells and Hela
      cells at 400 MUg/mL of NPs, while upon laser irradiation, effective cancer cell
      killing is observed at a NP concentration of 50 MUg/mL. Moreover, PFTTQ NPs could
      efficiently ablate tumor in in vivo study using a Hela tumor mouse model.
      Considering the large amount of NIR absorbing CPs available, the general
      encapsulation strategy will enable the development of more efficient PTT agents
      for cancer or tumor therapy. 

PMID- 25367502
TI  - Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self
      administration in rats.
AB  - The hypocretin/orexin (HCRT) system has been associated with both positive and
      negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in
      drug-related behaviors for all major drug classes, including opioids. However, to
      date there are limited studies investigating the role of HCRT receptor 2 (HCRT
      R2) signaling in compulsive-like drug seeking. Escalation of drug intake with
      extended access has been suggested to model the transition from controlled drug
      use to compulsive-like drug seeking/taking. The current study examined the
      effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats
      allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self
      administration. Results indicate that systemically administered NBI-80713 dose
      dependently decreased heroin self-administration in LgA, but not in ShA, animals.
      Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central
      amygdala, a stress-related brain region, of LgA rats. These observations suggest
      a functional role for HCRT-R2 signaling in compulsive-like heroin self
      administration associated with extended access and indicate HCRT-R2 antagonism as
      a potential pharmacological target for the treatment of heroin dependence.

PMID- 25367503
TI  - Involvement of cholinergic system in hyperactivity in dopamine-deficient mice.
AB  - Dopaminergic systems have been known to be involved in the regulation of
      locomotor activity and development of psychosis. However, the observations that
      some Parkinson's disease patients can move effectively under appropriate
      conditions despite low dopamine levels (eg, kinesia paradoxia) and that several
      psychotic symptoms are typical antipsychotic resistant and atypical antipsychotic
      sensitive indicate that other systems beyond the dopaminergic system may also
      affect locomotor activity and psychosis. The present study showed that dopamine
      deficient (DD) mice, which had received daily L-DOPA injections, could move
      effectively and even be hyperactive 72 h after the last L-DOPA injection when
      dopamine was almost completely depleted. Such hyperactivity was ameliorated by
      clozapine but not haloperidol or ziprasidone. Among multiple actions of
      clozapine, muscarinic acetylcholine (ACh) activation markedly reduced locomotor
      activity in DD mice. Furthermore, the expression of choline acetyltransferase, an
      ACh synthase, was reduced and extracellular ACh levels were significantly reduced
      in DD mice. These results suggest that the cholinergic system, in addition to the
      dopaminergic system, may be involved in motor control, including hyperactivity
      and psychosis. The present findings provide additional evidence that the
      cholinergic system may be targeted for the treatment of Parkinson's disease and
      psychosis.

PMID- 25367504
TI  - Optimal Duration of Dual Antiplatelet Therapy After Implantation of Drug-Eluting
      Stents: Shorter or Longer?
AB  - Use of dual antiplatelet therapy (DAPT; the combination of aspirin and an
      inhibitor of platelet P2Y12) is the key pharmacological component in the
      management of acute coronary syndrome and percutaneous coronary intervention
      (PCI) with stent implantation, but the optimal treatment duration is still
      unclear. Although current guidelines recommend prescription of DAPT for at least
      12 months after implantation of drug-eluting stents (DES) if patients are not at
      high risk of bleeding, several studies showed conflicting results. Observational
      studies have shown inconsistent findings (i.e., some studies suggested longer
      duration would be better, and others vice versa) and small-to-moderate sized
      randomized clinical trials suggested that prolonged use of DAPT beyond 12 months
      would not be more beneficial and could be detrimental in safety outcomes.
      However, these studies suffer from insufficient statistical power, data from old
      version of DES, and non-uniform duration of DAPT. Given there might be the
      relative risk and benefit associated with combination of DES use and DAPT
      prescription, the optimal decision making with regard to DAPT duration would be
      essential for patients who underwent PCI with DES. Thus, by understanding and
      comparing the evidences of recent studies that support for shorter and longer
      duration of DAPT, we sought to guide the treating physician in deciding optimal
      duration of DAPT in such patients. Up to now, there is no strong evidence
      supporting that longer duration of DAPT is better than shorter duration of DAPT
      in terms of efficacy and safety outcomes after DES placement. 

PMID- 25367505
TI  - Cutaneous drug toxicity from 2,4-dinitrophenol (DNP): Case report and
      histological description.
AB  - The use of 2,4-dinitrophenol (DNP) has regained popularity as a weight loss aid
      in the last two decades due to increased marketing to bodybuilders and the
      increasing availability of this banned substance via the Internet. 2,4-DNP is a
      drug of narrow therapeutic index and toxicity results in hyperthermia,
      diaphoresis, tachycardia, tachypnoea and possible cardiac arrest and death. Skin
      toxicity from 2,4-DNP has not been reported since the 1930s. We report a case of
      a 21-year-old bodybuilding enthusiast who presented with a toxic exanthem after
      taking 2,4-DNP, and describe the first skin biopsy findings in a case of 2,4-DNP
      toxicity. 

PMID- 25367507
TI  - Suicide among the youth in Malaysia: What do we know?
AB  - INTRODUCTION: This article aims to study the pattern of youth suicide cases in
      Malaysia, following which preventive actions can then be planned and practiced to
      reduce these suicide cases. METHODS: This is a cross-sectional study looking at
      notifications of all suicides involving members of the youth population, as had
      been reported to National Suicide Registry Malaysia from January 1, 2009 to
      December 31, 2009. Information such as profile demographics and methods of
      suicide were utilized accordingly. RESULTS: There were 53 youths between the ages
      of 15 and 24 years reported to have undergone completed suicides. The suicide
      rate among youths was 1.03 per 100,000 populations in 2009, accounting for the
      male gender (66.0%), with Indians being the highest suicide completers (40.4% and
      5.6 per 100,000 populations). The most common method of suicide was hanging
      (56.6%) followed by self-poisoning (15.1%). DISCUSSION: The suicide rate among
      Malaysian youth is relatively lower compared with other countries in the Asian
      region. Majority were male, of Indian descent, and were still in secondary
      school. Preventive actions need to be taken especially for specific groups such
      as the Indian youth.

PMID- 25367506
TI  - HSI2/VAL1 PHD-like domain promotes H3K27 trimethylation to repress the expression
      of seed maturation genes and complex transgenes in Arabidopsis seedlings.
AB  - BACKGROUND: The novel mutant allele hsi2-4 was isolated in a genetic screen to
      identify Arabidopsis mutants with constitutively elevated expression of a
      glutathione S-transferase F8::luciferase (GSTF8::LUC) reporter gene in
      Arabidopsis. The hsi2-4 mutant harbors a point mutation that affects the plant
      homeodomain (PHD)-like domain in HIGH-LEVEL EXPRESSION OF SUGAR-INDUCIBLE GENE2
      (HSI2)/VIVIPAROUS1/ABI3-LIKE1 (VAL1). In hsi2-4 seedlings, expression of this LUC
      transgene and certain endogenous seed-maturation genes is constitutively
      enhanced. The parental reporter line (WT LUC ) that was used for mutagenesis
      harbors two independent transgene loci, Kan R and Kan S . Both loci express
      luciferase whereas only the Kan R locus confers resistance to kanamycin. RESULTS:
      Here we show that both transgene loci harbor multiple tandem insertions at single
      sites. Luciferase expression from these sites is regulated by the HSI2 PHD-like
      domain, which is required for the deposition of repressive histone methylation
      marks (H3K27me3) at both Kan R and Kan S loci. Expression of LUC and Neomycin
      Phosphotransferase II transgenes is associated with dynamic changes in H3K27me3
      levels, and the activation marks H3K4me3 and H3K36me3 but does not appear to
      involve repressive H3K9me2 marks, DNA methylation or histone deacetylation.
      However, hsi2-2 and hsi2-4 mutants are partially resistant to growth inhibition
      associated with exposure to the DNA methylation inhibitor 5-aza-2'-deoxycytidine.
      HSI2 is also required for the repression of a subset of regulatory and structural
      seed maturation genes in vegetative tissues and H3K27me3 marks associated with
      most of these genes are also HSI2-dependent. CONCLUSIONS: These data implicate
      HSI2 PHD-like domain in the regulation of gene expression involving histone
      modifications and DNA methylation-mediated epigenetic mechanisms.

PMID- 25367508
TI  - The FlxABCD-HdrABC proteins correspond to a novel NADH
      dehydrogenase/heterodisulfide reductase widespread in anaerobic bacteria and
      involved in ethanol metabolism in Desulfovibrio vulgaris Hildenborough.
AB  - Flavin-based electron bifurcation (FBEB) is an important mechanism for the energy
      metabolism of anaerobes. A new family of NADH dehydrogenases, the flavin
      oxidoreductase (FlxABCD, previously called FloxABCD), was proposed to perform
      FBEB in sulphate-reducing organisms coupled with heterodisulfide reductase
      (HdrABC). We found that the hdrABC-flxABCD gene cluster is widespread among
      anaerobic bacteria, pointing to a general and important role in their
      bioenergetics. In this work, we studied FlxABCD of Desulfovibrio vulgaris
      Hildenborough. The hdr-flx genes are part of the same transcriptional unit and
      are increased in transcription during growth in ethanol-sulfate, and to a less
      extent during pyruvate fermentation. Two mutant strains were generated: one where
      expression of the hdr-flx genes was interrupted and another lacking the flxA
      gene. Both strains were unable to grow with ethanol-sulfate, whereas growth was
      restored in a flxA-complemented strain. The mutant strains also produced very
      reduced amounts of ethanol compared with the wild type during pyruvate
      fermentation. Our results show that in D. vulgaris, the FlxABCD-HdrABC proteins
      are essential for NADH oxidation during growth on ethanol, probably involving a
      FBEB mechanism that leads to reduction of ferredoxin and the small protein DsrC,
      while in fermentation they operate in reverse, reducing NAD(+) for ethanol
      production. 

PMID- 25367509
TI  - Impact of dietary fat source and concentration and daily fatty acid intake on the
      composition of carcass fat and iodine value sampled in three regions of the pork
      carcass.
AB  - The increased inclusion of unsaturated fats in pig diets has raised issues
      related to pork carcass fat quality. The objective of this experiment was to more
      precisely measure how differing levels of daily fatty acid intake alters the
      fatty acid composition in 3 different fat depots. A total of 42 gilts and 21
      barrows (PIC 337*C22/29) with an average initial weight of 77.80+/-0.38 kg were
      allotted randomly based on sex and BW to 7 treatments: 3 and 6% of each of tallow
      (TAL; iodine value [IV]=41.9), choice white grease (CWG; IV=66.5), or corn oil
      (CO; IV=123.1) and a control (CNTR) corn-soybean meal-based diet with no added
      fat. Pigs were individually housed to allow accurate measurement of individual
      feed intake, in particular, daily dietary fatty acid and energy intake. Fat
      samples were collected from the jowl, belly, and loin at slaughter. Diet and
      carcass fat samples were analyzed for IV. Belly weights were recorded at
      slaughter along with a subjective belly firmness score (1=firmest to 3=least
      firm). Carcass lipid IV was increased (P<0.001) by increasing the degree of
      unsaturation of the dietary fat source (66.8, 70.3, and 76.3 for TAL, CWG, and
      CO, respectively). Carcass lipid IV for TAL and CWG was not affected (P>0.05) by
      inclusion levels; however, carcass lipid IV was greater (P<0.001) in pigs fed 6
      than 3% CO (80.0 vs. 72.6), and carcasses of gilts had greater IV (P<0.001) than
      carcasses of barrows (71.5 vs. 69.1). Increasing the level of TAL and CO but not
      CWG from 3 to 6% decreased the apparent total tract digestibility of GE,
      resulting in a source*level interaction (P<0.05). Dietary fat source had no
      effect (P>=0.66) on apparent total tract digestibility of either DM or GE, but
      feeding 6% dietary fat increased G:F (P=0.006) over pigs fed 3% fat (0.358 vs.
      0.337). Of all the fatty acids measured, only linoleic acid intake presented a
      reasonable coefficient of determination (R2=0.61). Overall, IV product (IVP) was
      approximately equal to linoleic acid intake as a predictor of carcass IV (R2=0.93
      vs. R2=0.94). When inclusion of dietary fat and PUFA intake increased, IVP placed
      more emphasis on the dietary fat inclusion level rather than the dietary fat
      composition. Linoleic acid intake corrected the overemphasis placed on dietary
      fat inclusion by IVP. To conclude, linoleic acid intake showed a strong
      relationship with carcass IV and can be used as a predictor.

PMID- 25367510
TI  - Supplementing antioxidants to pigs fed diets high in oxidants: II. Effects on
      carcass characteristics, meat quality, and fatty acid profile.
AB  - The study was conducted to determine effects of dietary supplementation with a
      blend of antioxidants (ethoxyquin and propyl gallate) on carcass characteristics,
      meat quality, and fatty acid profile in finishing pigs fed a diet high in
      oxidants. A total of 100 crossbred barrows (10.9+/-1.4 kg BW, 36+/-2 d of age)
      were randomly allotted to 5 diet treatments (5 replicate pens per treatment, 4
      pigs per pen). Treatments included: 1) HO: high oxidant diet containing 5%
      oxidized soy oil and 10% PUFA source which contributed 5.56% crude fat and 2.05%
      docosahexanoic acid (DHA) to the diet; 2) VE: the HO diet with 11 IU/kg of added
      vitamin E; 3) AOX: the HO diet with antioxidant blend (135 mg/kg); 4) VE+AOX: the
      HO diet with both vitamin E and antioxidant blend; and 5) SC: a standard corn-soy
      control diet with nonoxidized oil and no PUFA source. The trial lasted for 118 d;
      on d 83, the HO diet pigs were switched to the SC diet due to very poor health.
      From that point, the VE pigs displayed the poorest performance. On d 118, 2 pigs
      from each pen were harvested for sampling. Compared to pigs fed SC diet, the HO
      and VE pigs (P<0.05) showed lighter carcass weight, less back fat, less lean body
      mass, and smaller loin eye area. In addition, the VE pigs had decreased dressing
      percentage than the AOX and VE+AOX pigs (65.7 vs. 75.3 and 74.2%). Compared to
      the SC pigs, greater moisture percentage (74.7 vs. 77.4%) and less extractable
      lipid content (2.43 vs. 0.95%) were found in VE fed pigs (P<0.05). Drip loss of
      loin muscle in VE pigs was less than SC pigs (0.46 vs. 3.98%, P=0.02), which was
      associated with a trend for a greater 24-h muscle pH (5.74 vs. 5.54, P=0.07). The
      antioxidant blend addition in the high oxidant diet attenuated all of these
      effects to levels similar to SC (P>0.05), except a* value (redness) and belly
      firmness. Visible yellow coloration of backfat and lipofuscin in HO and VE pigs
      was observed at harvest at d 118. The high oxidant diet resulted in greater
      concentration of DHA in backfat (P<0.001); switching the diet on d 83 resulted in
      HO pigs having a similar fatty acid profile to SC at d 118 pigs. Vitamin E
      concentration in plasma and muscle was greater in HO and SC than VE, AOX, and
      VE+AOX on d 118. Feeding the high oxidant diet caused a series of changes in
      carcass characteristics and meat quality. Addition of antioxidant blend
      attenuated many of these, whereas the protective effects of supplemental vitamin
      E at 11 IU/kg were minimal during the finisher phase of the study.

PMID- 25367511
TI  - Healing of surgical castration wounds: a description and an evaluation of
      flunixin.
AB  - Previous studies have shown that surgical castration wounds take between 10 and
      61 d to heal. The objectives of this work were to describe healing, inflammation,
      lying behavior, and serum concentration of substance P after surgical castration
      in beef calves and to evaluate the effect of a possible intervention, a single
      injection of flunixin meglumine (1.1 mg/kg IV, a NSAID), on the healing process.
      Calves (mean+/-SE: 25+/-2.0 d of age; 54+/-1.4 kg BW) were surgically castrated
      with or without an injection of flunixin immediately before the procedure
      (n=24/treatment). Healing was measured with a 5-point scale (1=fresh wound, 5=no
      visible incision or inflammation) as well as weight gain, scrotal size, and
      scrotal surface temperature, on d 1, 2, 3, 7, 14, 21, 28, 35, 49, and 63 after
      castration. Serum concentration of substance P was recorded on all d, including d
      0, but not d 63. Lying behavior was recorded with loggers from 2 d before to 29 d
      after castration. Inflammation, as measured by scrotal size, peaked on d 2 and 3
      after the procedure (e.g., 51+/-1.0 mm on d 2 versus 28+/-1.3 mm before
      castration) and then declined with time (P<0.001). The first wound to score as
      fully healed (i.e., 5/5) was seen on d 28; by d 63, 98% of wounds were fully
      healed. The greatest changes in healing score occurred between d 21 and 35; this
      was also the peak of wound surface temperature and may correspond with
      revascularization. Serum concentration of substance P was highest before
      castration (41+/-1.2 pg/mL), possibly because the sample was collected after the
      lidocaine ring block was administered, which was likely painful, and because of
      separation from the dam and restraint. Values began to drop by d 3 (34+/-1.2
      pg/mL) and leveled out by d 21 (30+/-1.2 pg/mL; P<0.001). Calves given flunixin
      had more lying bouts than those that received saline (flunixin by time
      interaction; P=0.052), but this pattern emerged on and after d 8, well after the
      3 to 8 h half-life of this NSAID. In conclusion, castration caused inflammation
      in the days that followed, and the wounds required a minimum of 4 wk to heal.
      Provision of an NSAID had no effect on these outcomes.

PMID- 25367512
TI  - Growth performance, blood metabolic responses, and carcass characteristics of
      grower and finisher South African Windsnyer-type indigenous and Large
      White*Landrace crossbred pigs fed diets containing ensiled corncobs.
AB  - A study was taken to evaluate growth performance, carcass characteristics, and
      blood metabolite concentrations when ensiled corncobs were included in indigenous
      and commercial pig diets. Fifty Large White* Landrace (LW*LR) crossbred pigs and
      30 South African Windsnyer-type indigenous pigs (SAWIP) were evaluated. They were
      fed a control (CON), a low inclusion of ensiled corncob (LMC), and a high
      inclusion of ensiled corncob (HMC) diet in a completely randomized block design.
      The LW*LR crosses had greater (P<0.05) final weight, ADFI, DMI, ADG, and G:F
      ratios than the SAWIP at both the grower and finisher stages. The SAWIP consumed
      more feed per metabolic BW (BW0.75) than LW*LR crosses at the grower stage while
      LW*LR crosses consumed more than SAWIP at the finisher stage (P<0.05). The
      finishers' G:F ratio was greater (P<0.05) in the CON than in the HMC diet. The
      LW*LR growers and finishers had greater (P<0.05) warm carcass weight (WCW), cold
      carcass weight (CCW), carcass length, drip loss, pH at 24 h, eye muscle area, and
      lean percent than those of SAWIP growers and finishers. The LW*LR finishers on
      the CON diet had greater (P<0.05) WCW and CCW than those on the HMC and LMC
      diets. There were diet*breed interactions for dorsal fat thickness at first rib
      (DFT1), dorsal fat thickness at last lumbar vertebra (DFT3), backfat thickness
      (BFT), and hindquarter weight proportion (HQWP) in the growers. The LW*LR growers
      and finishers had greater values (P<0.05) of hindquarter length, hindquarter
      circumference, HQWP, and shoulder weight proportion than the SAWIP growers and
      finishers, respectively. The SAWIP growers and finishers had greater values
      (P<0.05) of DFT1, dorsal fat thickness at last rib, DFT3, and BFT than the LW*LR
      growers and finishers, respectively. There were breed*diet interactions (P<0.05)
      for alanine aminotransferase and amylase (AMYL). The LW*LR crosses had greater
      (P< 0.05) values of creatinine, phosphorus, alkaline phosphatase, cholesterol,
      and AMYL than the SAWIP. The breed of pig influenced most of the growth
      performance and carcass parameters more than the diet did. There was no clear
      link between the blood metabolite levels and the diets. Since the inclusion of
      ensiled corncobs in diets did not affect negatively the selected important
      commercial pork cuts in South Africa, this could imply that they have a greater
      role as a pig feed resource.

PMID- 25367513
TI  - Performance and economic analyses of year-round forage systems for forage-fed
      beef production in the Gulf Coast.
AB  - On a global scale, most beef is produced from grazing pastures or rangelands.
      Certain limitations exist, however, such as not having adequate animal rates of
      gain for marbling and availability of adequate forage nutritional value and
      quantity for constant animal weight gains. In the last 20 yr, there has been an
      increased interest in forage-fed beef for multiple reasons (health related,
      environmental concerns, and welfare issues). Starting on June 5, 13, 14, and 8 in
      4 consecutive yr, 54 steers (initial BW=259+/-5.6 kg; average of 9 mo of age)
      were randomly allotted to 3 yr-round forage systems. Each system occupied 6
      ha/replicate and had the same stocking rate. System 1 had annual ryegrass (Lolium
      multiflorum) for winter grazing and bermudagrass (Cynodon dactylon) for summer
      grazing; while Systems 2 and 3 added rye and a clover mix to the ryegrass and
      diversified the use of pastures in the fall (dallisgrass [Paspalum dilatatum] and
      clovers [Trifolium spp.]). System 3 added the use of annual summer forages.
      During their respective growing season for each forage or forage mix, mass and
      height did not limit animal performance; however, there was a sampling date
      effect (P<0.05) for nutritive value variables since it decreased as forages
      became mature. The ADG observed (0.44 kg) for all systems (P=0.78) during summer
      was lower than expected and might have been limited by the observed temperature
      as well as forage nutritive value. Systems 1 and 2 had more grazing days (P=0.03)
      during summer (155 and 146 d, respectively) compared to System 3 (132 d) due to
      the greater pasture area of bermudagrass in those systems. Steers in System 3
      were fed more hay for a longer period of time (P<0.05) than on the other 2
      systems. System 1 and 2 produced more hay per hectare than System 3 (P<0.05). No
      differences (P>0.05) were detected between systems in ADG year round, during the
      winter season, or carcass characteristics. Return over total direct costs and
      total specified expenses were greater for Systems 1 and 2, while System 3 was the
      lowest. Hay making and bale sales played a major role in explaining the economic
      results of this study. Where possible, year-round forage systems are a viable
      alternative for forage-fed beef production; however, the low gains during summer
      and forage availability during the transition period when hay is necessary
      deserve further research to find alternatives to improve productivity during
      those times of the year.

PMID- 25367514
TI  - Short-term exposure to heat stress attenuates appetite and intestinal integrity
      in growing pigs.
AB  - Acute heat stress (HS) and heat stroke can be detrimental to the health, well
      being, and performance of mammals such as swine. Therefore, our objective was to
      chronologically characterize how a growing pig perceives and initially copes with
      a severe heat load. Crossbred gilts (n=32; 63.8+/-2.9 kg) were subjected to HS
      conditions (37 degrees C and 40% humidity) with ad libitum intake for 0, 2, 4, or
      6 h (n=8/time point). Rectal temperature (Tr), respiration rates (RR), and feed
      intake were determined every 2 h. Pigs were euthanized at each time point and
      fresh ileum and colon samples were mounted into modified Ussing chambers to
      assess ex vivo intestinal integrity and function. Transepithelial electrical
      resistance (TER) and fluorescein isothiocyanate-labeled dextran (FD4)
      permeability were assessed. As expected, Tr increased linearly over time
      (P<0.001) with the highest temperature observed at 6 h of HS. Compared to the 0-h
      thermal-neutral (TN) pigs, RR increased (230%; P<0.001) in the first 2 h and
      remained elevated over the 6 h of HS (P<0.05). Feed intake was dramatically
      reduced due to HS and this corresponded with significant changes in plasma
      glucose, ghrelin, and glucose-dependent insulinotropic peptide (P<0.050). At as
      early as 2 h of HS, ileum TER linearly decreased (P<0.01), while FD4 linearly
      increased with time (P<0.05). Colon TER and FD4 changed due to HS in quadratic
      responses over time (P=0.050) similar to the ileum but were less pronounced. In
      response to HS, ileum and colon heat shock protein (HSP) 70 mRNA and protein
      abundance increased linearly over time (P<0.050). Altogether, these data
      indicated that a short duration of HS (2-6 h) compromised feed intake and
      intestinal integrity in growing pigs.

PMID- 25367515
TI  - Supplementing antioxidants to pigs fed diets high in oxidants: I. Effects on
      growth performance, liver function, and oxidative status.
AB  - The objective of the study was to determine the effects of a dietary antioxidant
      blend (ethoxyquin and propyl gallate) and vitamin E on growth performance, liver
      function, and oxidative status in pigs fed diets high in oxidants. Crossbred
      barrows (n=100, 10.91+/-0.65 kg BW, 36+/-2 d of age, Landrace*Duroc) were
      allotted to 5 treatments on the basis of BW (5 replicate pens per treatment, 4
      pigs per pen). Treatments included 1) HO, high-oxidant diet containing 5%
      oxidized soybean oil and 10% PUFA source (providing 2.05% docosahexaenoic acid in
      the diet), 2) VE, the HO diet with 11 IU/kg of added vitamin E, 3) AOX, the HO
      diet with antioxidant blend (135 mg/kg), 4) VE+AOX, the HO diet with both vitamin
      E and antioxidant blend, and 5) SC, a standard corn-soy control diet. The trial
      lasted for 118 d; on d 83, the HO diet pigs were switched to the SC diet because
      the animals were displaying very poor health. Compared with SC pigs, HO pigs had
      decreased ADG (0.92 vs. 0.51 kg for d 26 to 55, 1.29 vs. 0.34 kg for d 56 to 82;
      P<0.05) and ADFI (1.84 vs. 0.96 kg for d 26 to 55, 3.41 vs. 1.14 kg for d 56 to
      82; P<0.05). However, switching the HO pigs to the SC diet resulted in HO pigs
      having a greater ADG than VE-fed pigs from d 83 to 118 (0.90 vs. 0.60 kg;
      P<0.05). The antioxidant blend restored pig performance to a level similar that
      of pigs fed the SC diet (P>0.05) with greater G:F for the entire period (0.44 vs.
      0.38; P<0.05). A greater liver to BW ratio was found in HO compared with other
      treatments on d 55 and in VE on d 118. Total bilirubin concentration in plasma of
      HO pigs on d 55 was greater than that in VE+AOX pigs (P<0.05), whereas on d 118,
      bilirubin concentration in VE was higher than those in VE+AOX and SC (P<0.05). A
      similar trend was observed in aspartate transaminase. Plasma concentrations of
      thiobarbituric acid reactive substances (TBARS) and carbonyl were elevated
      (P<0.05) in the HO pigs compared with the SC pigs on d 55 but not on d 118. Liver
      TBARS and carbonyl concentrations showed a similar trend, except that HO pigs had
      the greatest carbonyl concentration on d 118. Pigs fed AOX diets had plasma and
      liver TBARS and carbonyl concentrations similar to those fed SC diets. In the
      oxidative stress model used in this study, dietary addition of antioxidant blend
      or antioxidant blend+vitaimin E was effective in improving growth, liver
      function, and plasma markers of oxidative stress, but VE alone was not.

PMID- 25367516
TI  - Energy concentration and phosphorus digestibility in yeast products produced from
      the ethanol industry, and in brewers' yeast, fish meal, and soybean meal fed to
      growing pigs.
AB  - Two experiments were conducted to determine the DE, ME, and standardized total
      tract digestibility (STTD) of P in 2 novel sources of yeast (C-yeast and S-yeast)
      and in brewers' yeast, fish meal, and soybean meal fed to growing pigs. The 2 new
      sources of yeast are coproducts from the dry-grind ethanol industry. The
      concentrations of DM, GE, and P were 94.8%, 5,103 kcal/kg, and 1.07% in C-yeast;
      94.4%, 4,926 kcal/kg, and 2.01% in S-yeast; 93.6%, 4,524 kcal/kg, and 1.40% in
      brewers' yeast; 91.4%, 4,461 kcal/kg, and 3.26% in fish meal; and 87.7%, 4,136
      kcal/kg, and 0.70% in soybean meal, respectively. The DE and ME in each of the
      ingredients were determined using 42 growing barrows (28.9+/-2.18 kg BW). A corn
      based basal diet and 5 diets containing corn and 24% to 40% of each test
      ingredient were formulated. The total collection method was used to collect feces
      and urine, and the difference procedure was used to calculate values for DE and
      ME in each ingredient. The concentrations of DE in corn, C-yeast, S-yeast,
      brewers' yeast, fish meal, and soybean meal were 4,004, 4,344, 4,537, 4,290,
      4,544, and 4,362 kcal/kg DM (SEM=57), respectively, and the ME values were 3,879,
      3,952, 4,255, 3,771, 4,224, and 4,007 kcal/kg DM (SEM=76), respectively. The ME
      in S-yeast and fish meal were greater (P<0.05) than the ME in corn and brewers'
      yeast, whereas the ME in C-yeast and soybean meal were not different from those
      of any of the other ingredients. The STTD of P in the 5 ingredients was
      determined using 42 barrows (28.3+/-7.21 kg BW) that were placed in metabolism
      cages. Five diets were formulated to contain each test ingredient as the sole
      source of P, and a P-free diet was used to estimate the basal endogenous loss of
      P. Feces were collected for 5 d using the marker to marker method after a 5-d
      adaptation period. The STTD of P in brewers' yeast (85.2%) was greater (P<0.05)
      than the STTD of P in all the other ingredients except S-yeast (75.7%). The STTD
      of P in C-yeast (73.9%) was not different from the STTD of P in S-yeast and fish
      meal (67.3%) but was greater (P<0.05) than the STTD of P in soybean meal (56.7%).
      In conclusion, the 2 novel sources of yeast contain similar or greater
      concentrations of energy compared with brewers' yeast, corn, fish meal, and
      soybean meal, and the STTD of P in the 2 yeast products is not different from the
      STTD of P in fish meal.

PMID- 25367517
TI  - Effects of the porcine IGF2 intron 3-G3072A mutation on carcass cutability, meat
      quality, and bacon processing.
AB  - A SNP in a regulatory region of intron 3 within the porcine IGF2 gene (IGF2
      G3072A) is associated with increased lean deposition and decreased fat deposition
      in pigs with paternal A alleles (APat) compared with pigs with paternal G alleles
      (GPat). However, data regarding fresh and processed meat quality characteristics
      of pigs with different alleles for this polymorphism are limited. A single
      heterozygote (AG) boar was bred to homozygous (AA) commercial Yorkshire-cross
      sows producing F1 barrows and gilts with either GPat or APat. Two farrowing
      groups of barrows and gilts were group housed, provided ad libitum access to a
      diet that met or exceeded NRC nutrient recommendations throughout production, and
      slaughtered at 176 d (+/-4 d) of age. Fresh LM quality and estimated percent fat
      free lean measurements were taken on the left side of carcasses, while carcass
      cutouts were completed with right sides. Fresh belly and bacon processing traits
      were characterized for only block 1 pigs. Pig was treated as the experimental
      unit for all analyses. Ending live weight and HCW were not affected by IGF2
      allele; however, 10th rib backfat thickness was 0.41 cm less (P=0.01), loin eye
      area was 4.0 cm2 greater (P=0.01), and predicted fat-free lean was over 2
      percentage units greater (P<0.01) in APat pigs compared with GPat pigs.
      Furthermore, boneless lean cuts from the shoulder, loin, and ham were heavier
      (P<0.05) in APat pigs compared with GPat pigs. Minolta L* value was 2.36 units
      greater (P=0.03) but cooking loss was 1.82 percentage units greater (P<0.01) in
      APat pigs compared with GPat pigs. Additionally, despite reductions in
      subcutaneous fat, extractable intramuscular lipid from the LM was 0.64 percentage
      units greater (P=0.02) in APat pigs compared with GPat pigs. Bellies were 7.17 mm
      thinner (P=0.01), had 7.27 cm less flop distance (P=0.05), and tended to have
      1.34 units greater iodine value (P=0.09) in APat pigs compared with GPat pigs.
      While not statistically different (P=0.30), the magnitude of difference in
      slicing yield as a percentage of green weight was 1.57 percentage units between
      bellies from APat pigs (85.83%) and bellies from GPat pigs (87.40%). Pigs with
      GPat had superior belly quality that may positively impact commercial bacon
      production. However, pigs with APat yielded a greater amount of lean product at
      the expense of producing lighter LM color and increased cooking loss.

PMID- 25367518
TI  - Mechanistic model to predict colostrum intake based on deuterium oxide dilution
      technique data and impact of gestation and prefarrowing diets on piglet intake
      and sow yield of colostrum.
AB  - The aims of the present study were to quantify colostrum intake (CI) of piglets
      using the D2O dilution technique, to develop a mechanistic model to predict CI,
      to compare these data with CI predicted by a previous empirical predictive model
      developed for bottle-fed piglets, and to study how composition of diets fed to
      gestating sows affected piglet CI, sow colostrum yield (CY), and colostrum
      composition. In total, 240 piglets from 40 litters were enriched with D2O. The CI
      measured by D2O from birth until 24 h after the birth of first-born piglet was on
      average 443 g (SD 151). Based on measured CI, a mechanistic model to predict CI
      was developed using piglet characteristics (24-h weight gain [WG; g], BW at birth
      [BWB; kg], and duration of CI [D; min]: CI, g=-106+2.26 WG+200 BWB+0.111 D-1,414
      WG/D+0.0182 WG/BWB (R2=0.944). This model was used to predict the CI for all
      colostrum suckling piglets within the 40 litters (n=500, mean=437 g, SD=153 g)
      and was compared with the CI predicted by a previous empirical predictive model
      (mean=305 g, SD=140 g). The previous empirical model underestimated the CI by 30%
      compared with that obtained by the new mechanistic model. The sows were fed 1 of
      4 gestation diets (n=10 per diet) based on different fiber sources (low fiber
      [17%] or potato pulp, pectin residue, or sugarbeet pulp [32 to 40%]) from mating
      until d 108 of gestation. From d 108 of gestation until parturition, sows were
      fed 1 of 5 prefarrowing diets (n=8 per diet) varying in supplemented fat (3%
      animal fat, 8% coconut oil, 8% sunflower oil, 8% fish oil, or 4% fish oil+4%
      octanoic acid). Sows fed diets with pectin residue or sugarbeet pulp during
      gestation produced colostrum with lower protein, fat, DM, and energy
      concentrations and higher lactose concentrations, and their piglets had greater
      CI as compared with sows fed potato pulp or the low-fiber diet (P<0.05), and sows
      fed pectin residue had a greater CY than potato pulp-fed sows (P<0.05).
      Prefarrowing diets affected neither CI nor CY, but the prefarrowing diet with
      coconut oil decreased lactose and increased DM concentrations of colostrum
      compared with other prefarrowing diets (P<0.05). In conclusion, the new
      mechanistic predictive model for CI suggests that the previous empirical
      predictive model underestimates CI of sow-reared piglets by 30%. It was also
      concluded that nutrition of sows during gestation affected CY and colostrum
      composition.

PMID- 25367519
TI  - HORSE SPECIES SYMPOSIUM:  The aging horse: Effects of inflammation on muscle
      satellite cells.
AB  - With improvements in care, the equine population is living longer, remaining
      active, and competing at increasingly older ages. Both advancing age and exercise
      result in increased concentrations of circulating and local cytokines, including
      IL-1beta, IL-6, and tumor necrosis factor-alpha. Athletic endeavors in the aged
      horse may further increase the proinflammatory environment in muscle, decreasing
      the ability to react appropriately to exercise. Poor response to exercise limits
      the athletic ability of geriatric horses, thus reducing their useful life span
      and potentially increasing the risk of injury. Satellite cells are muscle stem
      cells that reside adjacent to muscle fibers in skeletal muscle and are at least
      partially responsible for maintenance of muscle mass and muscle hypertrophy. In
      the adult animal, these cells normally exist in a quiescent state, becoming
      active, proliferating, and differentiating in response to specific stimuli.
      Growth factors and cytokines present during hypertrophy and following exercise
      affect satellite cell activity. Whereas the specific effects of cytokines on
      equine satellite cells are not well established, cytokines can influence
      satellite cell and myoblast proliferation and differentiation both positively and
      negatively. Understanding the effects of cytokines on equine satellite cell
      function will provide insight into the mechanisms responsible for the poor
      response to exercise in the aged horse. The proinflammatory environment in aged
      horses may inhibit exercise induced satellite cell activity, thereby diminishing
      exercise-induced hypertrophy. As more horses are surviving and competing into
      their 20s, more research is required to understand the response of these animals
      to exercise during normal aging.

PMID- 25367520
TI  - A meta-analysis to identify animal and management factors influencing gestating
      sow efficiency.
AB  - A meta-analysis on the effects of management and animal-based factors on the
      reproductive efficiency of gestating sows can provide information on single
      factor and interaction effects that may not have been detected in individual
      studies. This study analyzed the effects of such factors on the number of piglets
      born alive per litter (BA), piglet birth weight (BiW) and weaning weight (WW),
      and number of piglets born alive per kilogram of sow feed intake during gestation
      (BA/FI). A total of 51 papers and 7 data sources were identified for the meta
      analysis, out of which 23 papers and 5 sets of production data were useable (a
      total of 121 treatments). The information gathered included the dependent
      variables as well as information regarding animal, management, and feed
      characteristics. While a number of factors were individually significant, the
      multivariate models identified significant effects only of 1) floor type
      (P=0.003), sow BW at the end of gestation (P=0.002), and housing (stalls vs.
      loose; P=0.004) on BA; as floor type and housing were confounded, they were
      included in 2 separate models. The BA was higher on solid (12.1) in comparison to
      partly slatted (11.4) and fully slatted floors (10.2); 2) sow gestation
      environment (P=0.017) and gestation feed allowance (P=0.046) on BiW, with BiW of
      pigs higher for sows kept outdoors rather than indoors (1.75 versus 1.49 kg); 3)
      parity number (P=0.003) and feed intake during gestation (P=0.017) on WW; in
      addition there was an interaction between parity number*feed ME and parity
      number*feed CP content of feed during gestation on WW, with the positive effects
      of feed ME and CP contents seen during early rather than later parities; and 4)
      floor type (P=0.019) and feed crude fiber (P=0.003) for BA/FI with a greater
      number for those kept on solid floors (5.11) versus partially and fully slatted
      floors (4.07 and 4.05). The meta-analysis confirmed the significant effect of
      several well-known factors on the efficiency of gestating sows and, importantly,
      the interactions between these factors. In addition, the effects of some less
      established factors were noted, such as floor type. The results may contribute
      towards the improvement of efficiency of gestating sow systems by better
      understanding of the various factors that influence this.

PMID- 25367521
TI  - In vitro effect of dietary protein level and nondigestible oligosaccharides on
      feline fecal microbiota.
AB  - The aim of the present study was to evaluate in vitro the effect of some
      prebiotic substances and 2 dietary protein levels on the composition and activity
      of feline fecal microbiota. Two in vitro studies were conducted. First, 6
      nondigestible oligosaccharides were studied; treatments were control diet (CTRL),
      gluconic acid (GA), carrot fiber (CF), fructooligosaccharides (FOS),
      galactooligosaccharides (GOS), lactitol (LAC), and pectins from citrus fruit
      (PEC). Substrates were added to feline fecal cultures at 2 g/L for 24 h
      incubation. Compared with the CTRL, ammonia had been reduced (P<0.05) by GOS (
      9%) after 6 h and by GA (-14%), LAC (-12%), and PEC (-10%) after 24 h. After 24
      h, all treatments had resulted in a lower pH versus the CTRL. Putrescine
      concentrations at 24 h were greater (P<0.05) in cultures treated with FOS (+90%),
      GOS (+96%), and LAC (+87%). Compared with the CTRL, total VFA were higher
      (P<0.05) in bottles containing CF (+41%), whereas the acetic to propionic acid
      ratio was reduced by LAC (-51%; P<0.05). After 24 h, Enterobacteriaceae had been
      reduced (P<0.05) by LAC and PEC. In a second study, LAC and FOS were selected to
      be tested in the presence of 2 diets differing in their protein content. There
      were 6 treatments: low-protein (LP) CTRL with no addition of prebiotics (CTRL
      LP), high-protein (HP) CTRL with no addition of prebiotics (CTRL-HP), LP diet
      plus FOS, CTRL-HP plus FOS, LP diet plus LAC, and CTRL-HP plus LAC. Both FOS and
      LAC were added to feline fecal cultures at 2 g/L for 24 h incubation. Ammonia at
      24 h was affected (P<0.05) by the protein level (36.2 vs. 50.2 mmol/L for LP and
      HP, respectively). The CTRL-HPs resulted in a higher pH and increased
      concentrations of biogenic amines were found after 6 and 24 h of incubation
      (P<0.05); putrescine at 24 h showed an increase (P<0.05) in cultures treated with
      FOS. Total VFA were influenced (P<0.05) by the protein level (40.9 vs. 32.6
      mmol/L for LP and HP, respectively). At 24 h, the CTRL-HPs were associated with
      increased Clostridium perfringens and reduced Lactobacillus spp. and enterococci
      counts (P<0.05). The results from the present study show that different
      prebiotics exert different effects on the composition and activity of feline
      intestinal microbiota and that high dietary protein levels in a cat's diet can
      have negative effects on the animal intestinal environment.

PMID- 25367522
TI  - Associations between pig adiponectin (ADIPOQ) genotype and serum lipid levels are
      modulated by age-specific modifiers.
AB  - The adiponectin (ADIPOQ) locus is a positional and functional candidate gene for
      2 porcine chromosome 13 (SSC13) QTL influencing cholesterol (CHOL) and low
      density lipoprotein (LDL) concentrations in 190-d-old pigs. By sequencing 2.37 kb
      of the pig ADIPOQ cDNA, we have identified 1 c.*1512G>T 3' untranslated region
      polymorphism that has been genotyped in a Duroc pig commercial population with
      records for serum lipid levels at 45 and 190 d of age. Statistical analysis of
      the data have revealed significant associations between the ADIPOQ genotype and
      CHOL (P=0.0040) and LDL (P=0.0011) concentrations at 190 d but not at 45 d. In
      family 3, most of the SSC13 QTL effects on LDL levels at 190 d were explained by
      the ADIPOQ genotype. We also found an association with triglyceride levels at 45
      d (P=0.0060) but not at 190 d. Measurement of allelic mRNA imbalance demonstrated
      that the G and T alleles are expressed at very similar levels in muscle and fat
      tissues, indicating that the c.*1512G>T polymorphism does not affect transcript
      abundance. As a whole, results obtained in the current work as well as previous
      data gathered in humans and pigs provide evidence that the magnitude of
      associations between blood lipid phenotypes and candidate loci genotypes may vary
      depending on the age of the individual, therefore suggesting the existence of
      dynamic genotype*environment interactions changing on a temporal scale.

PMID- 25367523
TI  - Estimating challenge load due to disease outbreaks and other challenges using
      reproduction records of sows.
AB  - A method was developed and tested to estimate challenge load due to disease
      outbreaks and other challenges in sows using reproduction records. The method was
      based on reproduction records from a farm with known disease outbreaks. It was
      assumed that the reduction in weekly reproductive output within a farm is
      proportional to the magnitude of the challenge. As the challenge increases beyond
      certain threshold, it is manifested as an outbreak. The reproduction records were
      divided into 3 datasets. The first dataset called the Training dataset consisted
      of 57,135 reproduction records from 10,901 sows from 1 farm in Canada with
      several outbreaks of porcine reproductive and respiratory syndrome (PRRS). The
      known disease status of sows was regressed on the traits number born alive,
      number of losses as a combination of still birth and mummified piglets, and
      number of weaned piglets. The regression coefficients from this analysis were
      then used as weighting factors for derivation of an index measure called
      challenge load indicator. These weighting factors were derived with i) a two-step
      approach using residuals or year-week solutions estimated from a previous step,
      and ii) a single-step approach using the trait values directly. Two types of
      models were used for each approach: a logistic regression model and a general
      additive model. The estimates of challenge load indicator were then compared
      based on their ability to detect PRRS outbreaks in a Test dataset consisting of
      records from 65,826 sows from 15 farms in the Netherlands. These farms differed
      from the Canadian farm with respect to PRRS virus strains, severity and frequency
      of outbreaks. The single-step approach using a general additive model was best
      and detected 14 out of the 15 outbreaks. This approach was then further validated
      using the third dataset consisting of reproduction records of 831,855 sows in 431
      farms located in different countries in Europe and America. A total of 41 out of
      48 outbreaks detected using data analysis were confirmed based on diagnostic
      information received from the farms. Among these, 30 outbreaks were due to PRRS
      while 11 were due to other diseases and challenging conditions. The results
      suggest that proposed method could be useful for estimation of challenge load and
      detection of challenge phases such as disease outbreaks. 

PMID- 25367524
TI  - Measurement of true ileal digestibility of phosphorus in some feed ingredients
      for broiler chickens.
AB  - An experiment was conducted to estimate the true ileal digestibility of P in
      wheat, sorghum, soybean meal, and corn distiller's dried grains with solubles
      (DDGS) in broiler chickens. Four semipurified diets were formulated from each
      ingredient (wheat and sorghum: 236.5, 473, 709.5, and 946 g/kg; soybean meal and
      corn DDGS: 135, 270, 405, and 540 g/kg) to contain graded concentrations of
      nonphytate P. The experiment was conducted as a randomized complete block design
      with 4 weight blocks of 16 cages each (5 birds per cage). A total of 320 21-d-old
      broilers (Ross 308) were assigned to the 16 test diets with 4 replicates per
      diet. Apparent ileal digestibility coefficients of P were determined by the
      indicator method and the linear regression method was used to determine the true
      P digestibility coefficients. The results showed that the apparent ileal P
      digestibility coefficients of wheat-based diets were not influenced (P>0.05) by
      increasing dietary P concentrations, whereas those of diets based on sorghum,
      soybean meal, and corn DDGS differed (P<0.05) at different P concentrations.
      Apparent ileal P digestibility in broilers fed diets with soybean meal and corn
      DDGS linearly (P<0.001) increased with increasing P concentrations. True ileal P
      digestibility coefficients of wheat, sorghum, soybean meal, and corn DDGS were
      determined to be 0.464, 0.331, 0.798, and 0.727, respectively. Ileal endogenous P
      losses in birds fed diets with wheat, soybean meal, and corn DDGS were estimated
      to be 0.080, 0.609, and 0.418 g/kg DMI, respectively. In birds fed sorghum-based
      diets, endogenous P losses were estimated to be negative (-0.087 g/kg DMI). True
      digestible P contents of wheat, sorghum, soybean meal, and corn DDGS were
      determined to be 1.49, 0.78, 5.16, and 5.94 g/kg, respectively. The corresponding
      nonphytate P contents in wheat, sorghum, soybean meal, and corn DDGS were 1.11,
      0.55, 2.15, and 4.36 g/kg, respectively. These differences between digestible P
      and nonphytate P contents may be suggestive, at least in part, of overestimation
      of P digestibility under the calcium-deficient conditions used in the regression
      method.

PMID- 25367525
TI  - Effects of physical restraint and electrical stunning on plasma corticosterone,
      postmortem metabolism, and quality of broiler breast muscle.
AB  - The objective of this study was to determine the effects of physical restraint
      and electrical stunning on plasma corticosterone, postmortem metabolism, and
      quality of broiler breast muscle. Before slaughter, a total of 160 Arbor Acres
      broilers were randomly categorized into 2 replicate pens (80 broilers per pen)
      and every pen was randomly divided into 4 groups (free struggle, physical
      restraint, free struggle and electrical stunning, and physical restraint and
      electrical stunning; n=20 per group). Glucose, lactate, and corticosterone were
      determined on blood plasma samples. Pectoralis major were removed after
      evisceration and used for determination of meat quality, energy metabolism, and
      calpain activity. In this study, reducing free struggle by physical restraint
      combined with electrical stunning improved (P<0.05) meat water holding capacity.
      Free struggle preslaughter and during bleeding increased (P<0.05) breast muscle
      redness, energy metabolism, and autolysis of MU/m-calpain and decreased (P<0.05)
      meat shear values. Physical restraint and electrical stunning decreased (P<0.05)
      plasma corticosterone level.

PMID- 25367526
TI  - A comparison of slice characteristics and sensory characteristics of bacon from
      immunologically castrated barrows with bacon from physically castrated barrows,
      boars, and gilts.
AB  - The objectives were to compare slice characteristics and sensory attributes of
      bacon from immunologically castrated (IC) barrows with bacon from other sexes
      using a trained sensory panel. Bacon was obtained for sensory evaluation from 3
      experiments. In Exp. 1, trimmed and squared bellies (n=180) of IC barrows, IC
      barrows fed ractopamine hydrochloride (IC+RAC), physically castrated (PC)
      barrows, intact males (IM), and gilts were used. Data were analyzed as a general
      linear mixed model and pen (n=48) served as the experimental unit. Treatment (sex
      or diet) was a fixed effect in all 3 experiments. In Exp. 2, untrimmed, natural
      fall bellies (n=96) from IC and PC barrows fed 0 or 30% or a withdrawal
      distillers dried grains with solubles (DDGS) program when slaughtered at 5 wk
      after the second dose (25 wk of age) were used. In Exp. 3, untrimmed, natural
      fall bellies (n=96) from IC and PC barrows fed the same experimental diets as in
      experiment 2 but slaughtered at 7 wk after the second dose (27 wk of age) were
      used. Data from Exp. 2 and 3 were analyzed as a 2*3 factorial arrangement in a
      randomized complete block design and pen was the experimental unit. Bellies from
      all 3 experiments were processed using the same protocols. In Exp. 1, IM had the
      greatest (P<0.0001) boar aroma and flavor scores among all treatments. No
      differences were detected among the other treatment groups for boar aroma or
      flavor. Intact males had the least (P<0.0001) desirable cured bacon aroma and
      flavor among all treatments. No differences were detected among the other
      treatment groups for bacon aroma or flavor. There were no differences in bacon
      aroma or off-flavor between IC and PC barrows slaughtered at 5 wk after the
      second dose regardless of DDGS feeding program. Bacon from PC barrows was saltier
      (P<0.01) than bacon from IC barrows when slaughtered at 5 wk after the second
      dose. There were no differences in bacon aroma, off-aroma, bacon flavor, or
      saltiness between IC and PC barrows slaughtered at 7 wk after the second dose
      regardless of DDGS feeding program. Total slice area of bacon slices from IC
      barrows slaughtered at 5 wk after the second dose were less (P<0.01) than PC
      barrows, but the differences diminished (P=0.16) when slaughtered at 7 wk after
      the second dose. Overall, panelists successfully detected boar odor and flavor in
      Exp. 1. Immunological castration was as effective as physical castration at
      eliminating boar aroma and boar flavor in bacon even when feeding differing DDGS
      feeding programs or when slaughtered at 5 or 7 wk after the second dose.

PMID- 25367527
TI  - Economic weights for maternal traits of sows, including sow longevity.
AB  - The objective of this study was to develop a transparent, comprehensive, and
      flexible model for each trait for the formulation of breeding objectives for sow
      traits in swine breeding programs. Economic values were derived from submodels
      considering a typical Australian pig production system. Differences in timing and
      expressions of traits were accounted for to derive economic weights that were
      compared on the basis of their relative size after multiplication by their
      corresponding genetic standard deviation to account for differences in scale and
      genetic variability present for each trait. The number of piglets born alive had
      the greatest contribution (27.1%) to a subindex containing only maternal traits,
      followed by daily gain (maternal; 22.0%) and sow mature weight (15.0%). Other
      traits considered in the maternal breeding objective were preweaning survival
      (11.8%), sow longevity (12.5%), gilt age at puberty (8.7%), and piglet survival
      at birth (3.1%). The economic weights for number of piglets born alive and
      preweaning piglet survival were found to be highly dependent on the definition of
      scale of enterprise, with each economic value increasing by approximately 100%
      when it was assumed that the value of extra output per sow could be captured,
      rather than assuming a consequent reduction in the number of sows to maintain a
      constant level of output from a farm enterprise. In the context of a full
      maternal line index that must account also for the expression of direct genetic
      traits by the growing piglet progeny of sows, the maternal traits contributed
      approximately half of the variation in the overall breeding objective. Deployment
      of more comprehensive maternal line indexes incorporating the new maternal traits
      described would lead to more balanced selection outcomes and improved survival of
      pigs. Future work could facilitate evaluation of the economic impacts of desired
      gains indexes, which could further improve animal welfare through improved sow
      and piglet survival. The results justify further development of selection
      criteria and breeding value prediction systems for a wider range of maternal
      traits relevant to pig production systems. 

PMID- 25367528
TI  - Effects of acid extrusion on the degradability of maize distillers dried grain
      with solubles in pigs.
AB  - Commonly used feed processing technologies are not sufficient to affect
      recalcitrant nonstarch polysaccharides (NSP) such as arabinoxylans present in
      maize distillers dried grain with solubles (DDGS). Instead, hydrothermal
      treatments combined with acid catalysts might be more effective to modify these
      NSP. The objective of this experiment was to investigate the effects of
      hydrothermal maleic acid treatment (acid extrusion) on the degradability of maize
      DDGS in growing pigs. It was hypothesized that acid extrusion modifies DDGS cell
      wall architecture and thereby increases fermentability of NSP. Two diets,
      containing either 40% (wt/wt) unprocessed or acid-extruded DDGS, were
      restrictedly fed to groups of gilts (n=11, with 4 pigs per group; initial mean
      BW: 20.8+/-0.2 kg) for 18 d and performance and digestibility were analyzed. Acid
      extrusion tended to decrease apparent ileal digestibility (AID) of CP
      (approximately 3 percentage units [% units]); P=0.063) and starch (approximately
      1% unit; P=0.096). Apparent digestibility of CP and starch measured at the mid
      colon (2% units, P=0.030, for CP and 0.3% units, P<0.01, for starch) and apparent
      total tract digestibility (ATTD; 3% units, P<0.01, for CP and 0.2% units,
      P=0.024, for starch) were lower for the acid-extruded diet compared with the
      control diet. Hindgut disappearance was, however, not different between diets,
      indicating that reduced CP and starch digestibility were mainly due to decreased
      AID. Acid extrusion tended to increase AID of NSP (6% units; P=0.092) and
      increased digestibility of NSP measured at the mid colon (6% units; P<0.01),
      whereas hindgut disappearance and ATTD of NSP did not differ between diets.
      Greater NSP digestibility was mainly due to greater digestibility of arabinosyl,
      xylosyl, and glucosyl residues, indicating that both arabinoxylan and cellulose
      degradability were affected by acid extrusion. In conclusion, these results show
      that acid extrusion did not improve degradation of DDGS for growing pigs.
      Although acid extrusion seemed to facilitate more rapid degradation of NSP and
      shifted fermentation to more proximal gastrointestinal segments, total extent of
      NSP degradation was not affected. More than 35% of the NSP from DDGS remained
      undegraded, independent of technological processing. Enzyme technologies that
      specifically target ester-linked acetyl, feroloyl, or coumaroyl groups were
      identified to be of interest for future research.

PMID- 25367529
TI  - Economic weights for performance and survival traits of growing pigs.
AB  - The objective of this paper was to derive economic weights for performance and
      survival traits of growing pigs including feed conversion ratio (FCR), daily feed
      intake (DFI), ADG, postweaning survival of the growing pig (SG), and carcass fat
      depth at the P2 site (CFD). An independent model was developed for each trait to
      derive economic values directly based on a typical Australian production system.
      This flexible approach may be used to customize economic values for different
      production systems and alternative trait combinations in breeding objectives.
      Discounted genetic expressions were used as a means of taking into account
      differences in frequency and timing of expression of traits to obtain economic
      weights. Economic values for SG were derived based on a cost-saving and a lost
      revenue approach. The correct formulation of the economic value of ADG depends on
      how feed cost is included in the breeding objective. If FCR is defined as a
      breeding objective trait, then savings in feed costs through earlier slaughter
      should not be counted in the economic value of ADG. In contrast, if DFI is
      included in the breeding objective instead of FCR, then feed-cost savings through
      earlier slaughter need to be attributed to the economic value for ADG, as a
      benefit from faster ADG. The paper also demonstrates that economic weightings in
      indexes for FCR can potentially be overestimated by 70% when it is assumed that
      DFI or FCR records taken from a limited duration test period reflect the
      corresponding trait over the full lifetime of the growing pig destined for
      slaughter. Postweaning survival of the growing pig was the most important
      breeding objective trait of growing pigs. The relative importance of each
      breeding objective trait in a sire-line index based on the genetic SD of each
      trait was 44.5, 27.0, 17.4, and 11.1% for SG, FCR, ADG, and CFD, respectively.
      Further studies to better clarify the extent of genetic variation that exists in
      SG under nucleus-farm and commercial-farm conditions are warranted, given the
      high economic importance of this survival trait of growing pigs. 

PMID- 25367531
TI  - Housing and Neighborhood Characteristics and Latino Farmworker Family Well-Being.
AB  - Housing quality and neighborhood characteristics affect individual health and
      family well-being. This analysis describes characteristics of farmworker housing
      and neighborhoods and delineates the associations of housing and local
      neighborhood with indicators of family well-being. Mothers in North Carolina
      farmworker families (n = 248) completed interviews in 2011-2012. Family well
      being measures included stress, family conflict, and outward orientation. Housing
      measures included ownership and facilities, and neighborhood measures included
      heavy traffic and driving time to grocery stores. Families experienced elevated
      stress and conflict, and limited outward orientation. Few owned their homes,
      which were generally crowded. Few had enclosed play spaces for their children.
      For many, traffic made it difficult to walk on the street. Housing and
      neighborhood characteristics were related to increased stress and limited outward
      orientation. Housing and neighborhood characteristics are important for research
      on the health of families in vulnerable populations, such as farmworker families.

PMID- 25367533
TI  - Should we mend their broken hearts? The history of cardiac repairs in children
      with Down syndrome.

PMID- 25367532
TI  - Variability in ADHD care in community-based pediatrics.
AB  - BACKGROUND: Although many efforts have been made to improve the quality of care
      delivered to children with attention-deficit/hyperactivity disorder (ADHD) in
      community-based pediatric settings, little is known about typical ADHD care in
      these settings other than rates garnered through pediatrician self-report.
      METHODS: Rates of evidence-based ADHD care and sources of variability (practice
      level, pediatrician-level, patient-level) were determined by chart reviews of a
      random sample of 1594 patient charts across 188 pediatricians at 50 different
      practices. In addition, the associations of Medicaid-status and practice setting
      (ie, urban, suburban, and rural) with the quality of ADHD care were examined.
      RESULTS: Parent- and teacher-rating scales were used during ADHD assessment with
      approximately half of patients. The use of Diagnostic and Statistical Manual of
      Mental Disorders criteria was documented in 70.4% of patients. The vast majority
      (93.4%) of patients with ADHD were receiving medication and only 13.0% were
      receiving psychosocial treatment. Parent- and teacher-ratings were rarely
      collected to monitor treatment response or side effects. Further, fewer than half
      (47.4%) of children prescribed medication had contact with their pediatrician
      within the first month of prescribing. Most variability in pediatrician-delivered
      ADHD care was accounted for at the patient level; however, pediatricians and
      practices also accounted for significant variability on specific ADHD care
      behaviors. CONCLUSIONS: There is great need to improve the quality of ADHD care
      received by children in community-based pediatric settings. Improvements will
      likely require systematic interventions at the practice and policy levels to
      promote change.

PMID- 25367530
TI  - Depressive Mood Among Within-Country Migrants in Periurban Shantytowns of Lima,
      Peru.
AB  - In low- and middle-income countries, migration to urban settings has reshaped the
      sprawl and socio demographic profiles of major cities. Depressive episodes make
      up a large portion of the burden of disease worldwide and are related to socio
      demographic disruptions. As a result of terrorism, political upheaval, followed
      by economic development, Peru has undergone major demographic transitions over
      the previous three decades including large migrations within the country. We
      aimed to determine the prevalence of current depressive mood and its relationship
      with parameters of internal migration, i.e. region of origin, age at migration,
      and years since migration. A community-wide census was carried out between
      January and June 2010 within a shantytown immigrant receiving community in Lima,
      Peru. One male or female adult per household completed a survey. Depressive mood
      was assessed with a 2-item Center for Epidemiologic Studies Depression (CESD)
      scale. Migration-related variables included place of birth, duration of residence
      in Lima, and age at migration. Prevalence ratios (PR) and 95% confidence
      intervals (95% CI) were calculated. A total of 8,551 out of 9,561 participants,
      response rate 89%, participated in the census. Of these, 8,091 records were
      analyzed: 71.8% were women [average age 39.4 (SD 13.9 years)] and 59.3% were
      immigrants. The overall prevalence of individuals with current depressive mood
      was 17.1% (95% CI 16.2-17.9%) and varied significantly by all socio-demographic
      and migration variables assessed. On unadjusted analyses, immigrants to Lima had
      higher prevalence of depressive mood if they originated in other costal or Andean
      areas, had lived in Lima for more than 20 years, or were <30 years of age when
      they out-migrated. When controlling for age, gender and socio-demographic
      variables the association was no longer significant, the only exception being a
      20% lower prevalence of current depressive mood among those who out-migrated aged
      >=30 years old (PR = 0.79; 95% CI 0.63-0.98). In conclusion, these results
      suggest that current depressive mood is very prevalent in this immigrant
      receiving community. Among all proxies for internal migration explored, in fully
      adjusted models, there was evidence of an association between age at migration
      (>=30 years old) and a lower probability of current depressive mood compared to
      non-migrants.

PMID- 25367534
TI  - Cobalamin C deficiency in an adolescent with altered mental status and anorexia.
AB  - Although cobalamin (cbl) C deficiency is the most common inherited disorder of
      vitamin B12 metabolism, the late-onset form of the disease can be difficult to
      recognize because it has a broad phenotypic spectrum. In this report, we describe
      an adolescent female exposed to unknown illicit substances and sexual abuse who
      presented with psychosis, anorexia, seizures, and ataxia. The patient's diagnosis
      was delayed until a metabolic workup was initiated, revealing
      hyperhomocysteinemia, low normal plasma methionine, and methylmalonic aciduria.
      Ultimately, cblC deficiency was confirmed when molecular testing showed compound
      heterozygosity for mutations (c.271dupA and c.482G>A) in the MMACHC gene. This
      diagnosis led to appropriate treatment with hydroxocobalamin, betaine, and
      folate, which resulted in improvement of her clinical symptoms and laboratory
      values. This patient demonstrates a previously unrecognized presentation of late
      onset cblC deficiency. Although neuropsychiatric symptoms are common in late
      onset disease, seizures and cerebellar involvement are not. Furthermore, anorexia
      has not been previously described in these patients. This case emphasizes that
      inborn errors of metabolism should be part of the differential diagnosis for a
      teenager presenting with altered mental status, especially when the diagnosis is
      challenging or neurologic symptoms are unexplained. Correct diagnosis of this
      condition is important because treatment is available and can result in clinical
      improvement.(1.) 

PMID- 25367535
TI  - Ablative fractional laser resurfacing helps treat restrictive pediatric scar
      contractures.
AB  - Conventional management of debilitating pediatric scar contractures, including
      hand therapy and surgery, may often be beset by delayed treatment, suboptimal
      results, and additional surgical morbidity. Ablative fractional laser resurfacing
      is an emerging adjunctive procedural option for scar contractures because of its
      promising efficacy and safety profile. However, its use to improve function has
      not been studied in the pediatric population. Herein we report 2 pediatric
      patients with recalcitrant scar contractures, causing persistent functional
      deficits, treated with an ablative fractional laser protocol. Both patients
      experienced rapid and cumulative subjective and objective improvements in range
      of motion and function as measured by an independent occupational therapist
      without reported complications. We highlight ablative fractional laser
      resurfacing as a novel and promising tool in the management of function-limiting
      scar contractures in children and propose that the technique be incorporated into
      existing scar treatment paradigms, guided by future research. 

PMID- 25367536
TI  - Fighting for the next generation: US Prematurity in 2030.
AB  - Preterm birth (PTB) is a serious problem, with >450 000 neonates born prematurely
      in the United States every year. Beginning in 1980, the United States experienced
      a nearly 3-decade rise in the PTB rate, peaking in 2006 at 12.8%. PTB has
      declined for 7 consecutive years to 11.4% in 2013, but it still accounts for 1 in
      9 neonates born every year. In addition to elevated neonatal and infant mortality
      among those born preterm, many who survive will have lifelong morbidities and
      disabilities. Because of the burden of morbidity, disability, and mortality for
      PTB, as well as its impact more broadly on society, including excess annual costs
      estimated to be at least $26.2 billion by a committee for the Institute of
      Medicine, the March of Dimes initiated the Prematurity Campaign in 2003. In 2008
      the March of Dimes established a goal of reducing the US PTB rate to 9.6% by
      2020. However, the United States ranks extremely poorly for PTB rates among Very
      High Human Development Index (VHHDI) countries, subjecting untold numbers of
      neonates to unnecessary morbidity and mortality. Therefore, the March of Dimes
      proposes an aspirational goal of 5.5% for the 2030 US PTB rate, which would put
      the United States in the top 4 (10%) of 39 VHHDI countries. This 5.5% PTB rate is
      being achieved in VHHDI countries and by women from diverse settings receiving
      optimal care. This goal can be reached and will ensure a better start in life for
      many more neonates in the next generation. 

PMID- 25367537
TI  - Becoming certified in "leadiatrics": what every pediatrician needs to do.

PMID- 25367538
TI  - Very low birth weight, infant growth, and autism-spectrum traits in adulthood.
AB  - OBJECTIVES: We examined whether adults born preterm at very low birth weight
      (VLBW; <1500 g) differ from term-born adults in autism-spectrum traits, and
      whether among VLBW adults, growth in infancy is associated with these traits.
      METHODS: A total of 110 VLBW and 104 term-born adults of the Helsinki Study of
      Very Low Birth Weight Adults completed the Autism-Spectrum Quotient yielding
      total, social interaction, and attention to detail sum scores. Growth in weight,
      length, and head circumference from birth to term and from term to 1 year of
      corrected age was determined as standardized residuals reflecting growth
      conditional on previous history. RESULTS: VLBW adults scored higher than term
      born controls on social interaction sum score, indicating higher autism-spectrum
      traits. In contrast, they scored lower on attention to detail sum score,
      indicating lower autism-spectrum traits. Within the VLBW group, faster growth in
      weight, length, and head circumference from birth to term was associated with
      lower total and social interaction sum scores. In this group, growth from term to
      1 year was not associated with autism-spectrum traits. CONCLUSIONS: Among those
      born preterm at VLBW, the risk for higher levels of autism-spectrum traits,
      particularly related to social interaction, may persist into adulthood. Faster
      growth from birth to term may ameliorate these effects, suggesting that targeted
      interventions could aid long-term neurodevelopment.

PMID- 25367539
TI  - Unconditional regard buffers children's negative self-feelings.
AB  - BACKGROUND: Unconditional regard refers to the feeling that one is accepted and
      valued by others without conditions. Psychological theory suggests that
      experiences of unconditional regard lead children to feel that they are valuable
      despite setbacks. We hypothesized that reflecting on experiences of unconditional
      regard would buffer children's negative self-feelings (eg, shame, insecurity,
      powerlessness) in the face of setbacks. To test this hypothesis, we randomized
      children to reflect on experiences of unconditional regard or other experiences,
      and examined their response to an academic setback 3 weeks later. METHODS:
      Participants (11-15 years old) were randomly assigned to reflect for 15 minutes
      on experiences of unconditional regard (n = 91), conditional regard (n = 80), or
      other social experiences (n = 76). Research personnel, teachers, and classmates
      remained blind to condition assignment. Three weeks later, after receiving their
      course grades, children reported their self-feelings. Course grades were obtained
      from school records. Receiving low course grades represents a salient and painful
      real-world setback for children. RESULTS: Replicating previous research, children
      who received lower grades experienced more negative self-feelings (P < .001). As
      predicted, this well-established relationship was significantly attenuated among
      children who had reflected, 3 weeks previously, on experiences of unconditional
      regard (Ps < .03). Reflecting on unconditional regard specifically reduced
      negative self-feelings after low grades (P = .01), not after average or high
      grades (Ps > .17). CONCLUSIONS: Reflecting on unconditional regard buffered
      children's selves against the adverse impact of an academic setback over an
      extended period of time. Unconditional regard may thus be an important
      psychological lever to reduce negative self-feelings in youth.

PMID- 25367541
TI  - The missing link of NIH funding in pediatric research training program
      restructuring.

PMID- 25367540
TI  - Early developmental outcomes of children with congenital HHV-6 infection.
AB  - OBJECTIVE: The goal of this study was to determine if congenital human
      herpesvirus-6 (HHV-6) infection influences early neurodevelopment. METHODS: We
      enrolled 57 newborns with HHV-6 congenital infection and 242 control newborns
      without congenital infection into a prospective, double-blind study with 4 visits
      between 4 and 30 months of age. Assessments included the Fagan Test of Infant
      Intelligence, the Visual Expectation Paradigm, and the Mental Development Index
      (MDI) of the Bayley Scales of Infant Development II. Newborn audiology screening
      and follow-up audiology examinations were completed at 12 to 24 months. RESULTS:
      No differences were noted in baseline characteristics between infants with HHV-6
      congenital infection and control infants. No clinical syndrome due to congenital
      infection with HHV-6 was evident at birth. No differences were identified on the
      Fagan Test of Infant Intelligence or the Visual Expectation Paradigm between the
      two groups. In 39 infants with HHV-6 congenital infection, the mean +/- SD Bayley
      Scale of Infant Development II MDI score was 103.4 +/- 8.9 at 12 months of age.
      The matched control infants had a mean score of 105.4 +/- 12.4. After controlling
      for covariates, HHV-6 congenital infection was associated with lower scores on
      the Bayley Scale of Infant Development II MDI at 12 months of age (mean
      difference: 4.3 [95% confidence interval: 0.4 to 8.1]; P = .03) compared with
      infants without HHV-6 congenital infection. CONCLUSIONS: Congenital HHV-6
      infection may have a detrimental effect on neurodevelopment at 12 months of age
      and requires further study given that congenital infection with HHV-6 is present
      in ~1 in every 101 births.

PMID- 25367542
TI  - Gender differences in adult-infant communication in the first months of life.
AB  - OBJECTIVES: To evaluate the verbal interactions of parents with their infants in
      the first months of life and to test the hypothesis that reciprocal vocalizations
      of mother-infant dyads would be more frequent than those of father-infant dyads.
      METHODS: This prospective cohort study included 33 late preterm and term infants.
      Sixteen-hour language recordings during the birth hospitalization and in the home
      at 44 weeks' postmenstrual age (PMA) and 7 months were analyzed for adult word
      count, infant vocalizations, and conversational exchanges. RESULTS: Infants were
      exposed to more female adult speech than male adult speech from birth through 7
      months (P < .0001). Compared with male adults, female adults responded more
      frequently to their infant's vocalizations from birth through 7 months (P <
      .0001). Infants preferentially responded to female adult speech compared with
      male adult speech (P = .01 at birth, P < .0001 at 44 weeks PMA and 7 months).
      Mothers responded preferentially to girls versus boys at birth (P = .04) and 44
      weeks PMA (P = .0003) with a trend at 7 months (P = .15), and there were trends
      for fathers to respond preferentially to boys at 44 weeks PMA (P = .10) and 7
      months (P = .15). CONCLUSIONS: Mothers provide the majority of language input and
      respond more readily to their infant's vocal cues than fathers; infants show a
      preferential vocal response to their mothers in the first months. Findings also
      suggest that parents may also respond preferentially to infants based on gender.
      Informing parents of the power of early talking with their young infants is
      recommended.

PMID- 25367543
TI  - Health outcomes in young adults from foster care and economically diverse
      backgrounds.
AB  - BACKGROUND AND OBJECTIVES: Foster youth have high rates of health problems in
      childhood. Little work has been done to determine whether they are similarly
      vulnerable to increased health problems once they transition to adulthood. We
      sought to prospectively evaluate the risk of cardiovascular risk factors and
      other chronic conditions among young adults formerly in foster care (FC) and
      young adults from economically insecure (EI) and economically secure (ES)
      backgrounds in the general population. METHODS: We used data from the Midwest
      Evaluation of the Adult Functioning of Former Foster Youth (FC group; N = 596)
      and an age-matched sample from the National Longitudinal Study of Adolescent
      Health (EI and ES groups; N = 456 and 1461, respectively). After controlling for
      covariates, we performed multivariate regressions to evaluate health outcomes and
      care access by group at 2 time points (baseline at late adolescence, follow-up at
      25-26 years). RESULTS: Data revealed a consistent pattern of graduated increase
      in odds of most health outcomes, progressing from ES to EI to FC groups. Health
      care access indicators were more variable; the FC group was most likely to report
      having Medicaid or no insurance but was least likely to report not getting needed
      care in the past year. CONCLUSIONS: Former foster youth appear to have a higher
      risk of multiple chronic health conditions, beyond that which is associated with
      economic insecurity. Findings may be relevant to policymakers and practitioners
      considering the implementation of extended insurance and foster care programs and
      interventions to reduce health disparities in young adulthood.

PMID- 25367544
TI  - Parent-implemented social intervention for toddlers with autism: an RCT.
AB  - OBJECTIVES: To compare the effects of two 9-month parent-implemented
      interventions within the Early Social Interaction (ESI) Project. Both individual
      ESI, offered 2 or 3 times per week at home or in the community, and group-ESI,
      offered once per week in a clinic, taught parents how to embed strategies to
      support social communication throughout everyday activities. METHODS:
      Participants in the randomized controlled trial included 82 children diagnosed
      with autism spectrum disorder at 16 to 20 months. Children were matched on
      pretreatment nonverbal developmental level and pairs were randomly assigned to
      treatment condition. Child outcomes included measures of social communication,
      autism symptoms, adaptive behavior, and developmental level. Child outcomes are
      reported from baseline to the end of the 9-month interventions. RESULTS: Children
      in individual-ESI showed differential change on a standardized examiner
      administered observational measure of social communication, as they improved at a
      faster rate than children in group-ESI. Individual-ESI also showed differential
      efficacy on a parent report measure of communication, daily living, and social
      skills, as they showed improvement or stability, whereas group-ESI led to
      worsening or no significant change on these skills. Finally, individual-ESI
      showed differential change on examiner-administered measures of receptive
      language skills, as children in individual-ESI improved significantly, whereas
      group-ESI showed no change. CONCLUSIONS: These findings support the efficacy of
      individual-ESI compared with group-ESI on child outcomes, suggesting the
      importance of individualized parent coaching in natural environments. The
      efficacy of a parent-implemented intervention using little professional time has
      potential for community viability, which is particularly important in light of
      the lack of main effects on child outcomes of most other parent-implemented
      interventions.

PMID- 25367545
TI  - A randomized trial on screening for social determinants of health: the iScreen
      study.
AB  - BACKGROUND: There is growing interest in clinical screening for pediatric social
      determinants of health, but little evidence on formats that maximize disclosure
      rates on a wide range of potentially sensitive topics. We designed a study to
      examine disclosure rates and hypothesized that there would be no difference in
      disclosure rates on face-to-face versus electronic screening formats for items
      other than highly sensitive items. METHODS: We conducted a randomized trial of
      electronic versus face-to-face social screening formats in a pediatric emergency
      department. Consenting English-speaking and Spanish-speaking adult caregivers
      familiar with the presenting child's household were randomized to social
      screening via tablet computer (with option for audio assist) versus a face-to
      face interview conducted by a fully bilingual/bicultural researcher. RESULTS:
      Almost all caregivers (96.8%) reported at least 1 social need, but rates of
      reporting on the more sensitive issues (household violence and substance abuse)
      were significantly higher in electronic format, and disclosure was marginally
      higher in electronic format for financial insecurity and neighborhood and school
      safety. There was a significant difference in the proportion of social needs
      items with higher endorsement in the computer-based group (70%) than the face-to
      face group (30%). CONCLUSIONS: Pediatric clinical sites interested in
      incorporating caregiver-reported socioeconomic, environmental, and behavioral
      needs screening should consider electronic screening when feasible, particularly
      when assessing sensitive topics such as child safety and household member
      substance use.

PMID- 25367546
TI  - Black, yellow, or silver: which one leads skin pattern formation?

PMID- 25367547
TI  - Achilles tendinopathy: A prospective study on the effect of active rehabilitation
      and steroid injections in a clinical setting.
AB  - In published efficacy studies on Achilles tendinopathy (AT) exercise alone
      results in improvement in 60-90% of the cases. However, this high success rate
      cannot be expected in usual clinical practice. We prospectively investigated the
      effectiveness of a treatment regimen consisting of home-based exercises
      (concentric, eccentric, and stretching) and optional glucocorticosteroid (GCS)
      injections in patients with (AT) in a usual clinical setting. Patients unable to
      commence or progress in exercise were offered GCS, hypothesizing that the GCS
      would facilitate exercise. Ninety-three consecutive patients with AT referred to
      two outpatient rheumatology clinics were registered, and seen at five visits over
      a 6-month period. Exercises seemed to have a slow, but long-lasting effect with
      GCS having a dramatic short-term effect on symptoms. Twenty-six percent of the
      patients could proceed with training alone, the remainder received one to three
      supplementary GCS. There were significant improvements on all outcome variables
      over time (P <= 0.001). At follow-up, 42 had no more symptoms, 29 good result, 16
      slightly improved, 4 unchanged, and 2 slightly worse. Overall, 94% of the
      patients had improved, and we thus recommend the use of GCS injections in AT
      patients if training alone does not lead to improvement. 

PMID- 25367548
TI  - Morbidity and mortality risk ratios are elevated in severe supine dominant OSA: a
      long-term follow-up study.
AB  - PURPOSE: Obstructive sleep apnoea (OSA) is a common public health problem.
      Sleeping position dependency has been related to OSA, and around half of OSA
      patients suffer from positional OSA where majority of the respiratory events
      occur in supine position. The consequences of supine dominant OSA have not been
      thoroughly investigated in long-term follow-up studies. The aim of the study was
      to retrospectively investigate the effects of supine dominant OSA on morbidity
      and mortality risk ratios during long-term follow-up and compare the findings
      with a non-supine OSA group at different OSA severities. METHODS: Ambulatory
      polygraphic recordings of 793 patients with median follow-up time of 194.5 months
      were retrospectively analysed. The risk ratios of morbidity and mortality of
      supine dominant OSA and non-supine OSA patients were compared. RESULTS: Supine
      dominant OSA patients, having majority of the obstruction events occurring in
      supine position, showed higher mortality and morbidity risk ratios in severe OSA
      category than the non-supine OSA patients. In severe category, the observed risk
      ratios were statistically significant. CONCLUSIONS: The increased risk ratios of
      mortality and morbidity found further emphasises that supine OSA might have more
      severe health consequences than non-positional OSA especially in severe OSA.
      Severe OSA occurring in supine position was shown to be more deleterious than non
      supine OSA based on long-term mortality and morbidity evidence.

PMID- 25367549
TI  - Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long
      term Spanish experience.
AB  - Lipodystrophies are a group of diseases mainly characterized by a loss of adipose
      tissue and frequently associated with insulin resistance, hypertriglyceridemia,
      and hepatic steatosis. In uncommon lipodystrophies, these complications
      frequently are difficult to control with conventional therapeutic approaches.
      This retrospective study addressed the effectiveness of recombinant methionyl
      leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic
      steatosis in patients with genetic lipodystrophic syndromes. We studied nine
      patients (five females and four males) with genetic lipodystrophies [seven with
      Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with
      type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under
      age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and
      hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was
      self-administered subcutaneously daily at a final dose that ranged between 0.05
      and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The
      duration of treatment ranged from 9 months to 5 years, 9 months (median: 3
      years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin
      and leptin, and hepatic enzymes were evaluated at baseline and at least every 6
      months. Except for the patient with FPLD, metreleptin replacement significantly
      improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma
      triglycerides were reduced 76 % on average, and hepatic enzymes decreased more
      than 65 %. This study extends knowledge about metreleptin replacement in genetic
      lipodystrophies, bearing out its effectiveness for long periods of time.

PMID- 25367550
TI  - Gender-related clinical and echocardiographic outcomes at 30-day and 12-month
      follow up after MitraClip implantation in the GRASP registry.
AB  - OBJECTIVES: To assess the influence of patients' gender on the outcomes of
      percutaneous edge-to-edge mitral valve repair (PMVR) using the MitraClip system.
      BACKGROUND: Although gender-related differences have been extensively documented
      in patients who undergo surgery for moderate-to-severe (3+) and severe (4+)
      mitral regurgitation (MR), studies assessing whether these differences exist
      after PMVR are lacking. METHODS: Clinical and echocardiographic data through 12
      month follow up from 171 consecutive patients whom underwent MitraClip
      implantation and were dichotomized by the gender (106 males and 65 females) were
      obtained. The primary safety endpoint was the incidence of major adverse events
      at 30 days and the primary efficacy endpoint was freedom from death, surgery for
      mitral valve dysfunction, or grade>=3+ MR at 12-month follow up. RESULTS: The
      primary safety endpoint was observed in four males (3.8%) and four females (6.2%)
      (P=0.358). Remarkable reduction in MR postprocedure was revealed in both groups,
      and these results were mostly sustained. Furthermore, left ventricle reverse
      remodeling and New York Heart Association (NYHA) functional class improvement
      were revealed in both groups, but females tended to demonstrate worse results
      over time (P=0.083). The primary efficacy endpoint obtained by Kaplan-Meier
      estimates was observed in 76.3 and 70.2%, respectively (log rank P=0.231).
      CONCLUSIONS: MitraClip implantation in patients with 3+ and 4+ MR is safe and
      efficacious until mid-term follow up, regardless of patients' gender. Despite
      improvement in NYHA functional class in both groups, female gender demonstrated a
      trend toward poorer results. Further validation of our findings is warranted.

PMID- 25367551
TI  - A priming dose of intravenous ketamine-dexmedetomidine suppresses fentanyl
      induced coughing: a double-blind, randomized, controlled study.
AB  - OBJECTIVE: This study was designed to investigate whether a priming dose of
      ketamine-dexmedetomidine can effectively suppress fentanyl-induced coughing
      (FIC). METHODS: Altogether 400 patients of ASA I and II, aged 18-70 years,
      undergoing various elective surgical procedures, were randomly allocated into
      four groups of 100 patients each. Patients in the placebo group received volume
      matched normal saline 0.15 mL/kg + normal saline 0.05 mL/kg. One group of
      patients was given ketamine 0.15 mg/kg + normal saline 0.05 ml/kg (KET), and
      another group dexmedetomidine 0.5 MUg/kg + normal saline 0.05 ml/kg (DEX).
      Finally, one group of patients received ketamine 0.15 mg/kg + dexmedetomidine 0.5
      MUg/kg (KETODEX). After fentanyl administration, the onset time and severity of
      cough for 1 min were recorded. Cough severity was graded as mild (grade 1-2),
      moderate (grade 3-5), or severe (grade >5). RESULT: The incidence of FIC was 53%,
      34%, 20%, and 9% in the placebo, DEX, KET, and KETODEX groups, respectively. The
      incidence of cough was significantly lower in the KETODEX group. Likewise, the
      onset time of cough was significantly delayed in the KETODEX group. Only nine
      patients in the KETODEX group had either mild (6%) or moderate (3%) cough, with
      none suffering from severe cough. CONCLUSION: A priming dose of KETODEX
      effectively suppressed the cough reflex induced by fentanyl and delayed the onset
      time of cough. Therefore, treatment with KETODEX may be a clinically useful
      method for preventing FIC.

PMID- 25367552
TI  - Autonomous exoskeleton reduces metabolic cost of human walking.
AB  - BACKGROUND: Passive exoskeletons that assist with human locomotion are often
      lightweight and compact, but are unable to provide net mechanical power to the
      exoskeletal wearer. In contrast, powered exoskeletons often provide biologically
      appropriate levels of mechanical power, but the size and mass of their
      actuator/power source designs often lead to heavy and unwieldy devices. In this
      study, we extend the design and evaluation of a lightweight and powerful
      autonomous exoskeleton evaluated for loaded walking in (J Neuroeng Rehab 11:80,
      2014) to the case of unloaded walking conditions. FINDINGS: The metabolic energy
      consumption of seven study participants (85 +/- 12 kg body mass) was measured
      while walking on a level treadmill at 1.4 m/s. Testing conditions included not
      wearing the exoskeleton and wearing the exoskeleton, in both powered and
      unpowered modes. When averaged across the gait cycle, the autonomous exoskeleton
      applied a mean positive mechanical power of 26 +/- 1 W (13 W per ankle) with 2.12
      kg of added exoskeletal foot-shank mass (1.06 kg per leg). Use of the leg
      exoskeleton significantly reduced the metabolic cost of walking by 35 +/- 13 W,
      which was an improvement of 10 +/- 3% (p = 0.023) relative to the control
      condition of not wearing the exoskeleton. CONCLUSIONS: The results of this study
      highlight the advantages of developing lightweight and powerful exoskeletons that
      can comfortably assist the body during walking.

PMID- 25367553
TI  - Evaluation of the regional ventricular systolic function by two-dimensional
      strain echocardiography in gestational diabetes mellitus (GDM) fetuses with good
      glycemic control.
AB  - OBJECTIVE: The aim is to quantitatively assess regional ventricular systolic
      function by two-dimensional strain (2DS) echocardiography in gestational diabetes
      mellitus (GDM) fetuses with good glycemic control. METHODS: We studied 60
      consecutive normal fetuses and 35 fetuses of GDM mothers with good glycemic
      control by echocardiography. M-mode and two-dimensional echocardiography were
      used to measure ejection fraction and wall dimensions of left ventricle and right
      ventricle. Both left and right ventricle peak systolic myocardial strain values
      were obtained by 2DS echocardiography. RESULTS: Compared with normal fetuses, the
      thickness of the interventricular septum (IVS) and the thickness of right
      ventricular wall were significantly increased in GDM fetuses (p < 0.05). Compared
      with those of normal fetuses, the peak systolic myocardial strain decreased
      significantly in the apical segments of the IVS and the apical segments of the
      left ventricular lateral wall in GDM fetuses (p < 0.05), as well as the apical
      and middle segments of right ventricular wall in GDM fetuses (p < 0.05). Peak
      negative 2DS values in 60 normal fetuses increased with the gestational age,
      showing a significant linear correlation(r = -0.625, p < 0.001). The average
      ventricular strain was not correlated to ventricular wall thickness (r = 0.127, p
      = 0.394). CONCLUSIONS: 2DS is a feasible approach to assess regional ventricular
      systolic function in the fetal hearts and it can be used to examine cardiac
      systolic function in GDM fetuses with good glycemic control.

PMID- 25367554
TI  - Two-dimensional sonographic assessment of maximum placental length and thickness
      in the second trimester: a reproducibility study.
AB  - OBJECTIVES: To determine the most reproducible method for the sonographic
      measurement of placental length. METHODS: A prospective study of women with
      singleton pregnancies who underwent sonographic measurement of placental
      dimensions during mid-gestation. Two sonographers independently determined
      placental length using three different approaches (linear, curve-linear and
      panoramic) and placental thickness. Reproducibility was assessed by the Bland
      Altman method and Interclass Correlation Coefficient (ICC). RESULTS: Overall 34
      women were included in the study. The curve-linear approach for the measurement
      of placental length was associated with the highest reproducibility (mean inter
      observer difference of -0.10 cm) compared to the linear and panoramic approaches
      (mean difference -0.15 cm and -0.29 cm, respectively). Similarly, the ICC was
      highest for the curve-linear length approach (0.974) compared with the linear
      length and panoramic length approaches (0.956 and 0.926, respectively).
      Measurements of maximum placental thickness was also associated with a very good
      ICC (0.954). CONCLUSIONS: The curve-linear method for the measurement of
      placental length in the 2nd trimester appears to be the most reproducible
      approach. This technique may prove useful as an adjunct screening method, along
      with uterine artery Doppler and maximum placental thickness, to screen for major
      placental complications of pregnancy in the second trimester.

PMID- 25367555
TI  - Prediction of cardiovascular risk by electrocardiographic changes in women with
      intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVE: We aimed to investigate P wave characteristics in pregnant women with
      and without intrahepatic cholestasis of pregnancy (ICP). METHODS: In this case
      control study, including 59 pregnant women with intrahepatic cholestasis and 28
      with healthy uncomplicated pregnancies, electrocardiographic maximum (Pmax) and
      minimum (Pmin) P-wave durations and P-wave dispersion (Pd) parameters were
      investigated. RESULTS: While Pmin and Pd values were significantly lower in women
      both with mild and severe ICP when compared to healthy pregnant women (p <
      0.001), there was no significant difference between mild and severe disease
      groups. CONCLUSION: Intrahepatic cholestasis predisposes to cardiovascular
      complications. P-wave durations and Pd constitute a recent contribution to the
      field of noninvasive electrocardiology. Our data clearly demonstrated that these
      parameters were significantly altered in pregnant women with ICP when compared to
      the normal ones. This important association can be used to screen for women with
      an increased risk to better target counseling on lifestyle modifications and to
      closer follow-up and management of women with a history of ICP.

PMID- 25367556
TI  - Are vital signs indicative for bacteremia in newborns?
AB  - OBJECTIVE: Neonatal systemic infection is a leading cause of morbidity and
      mortality both in industrialized and developing countries. The aim of this
      prospective study was to evaluate if vital signs had a predictive power in
      neonatal sepsis as an early marker. METHODS: This study was designed as a matched
      case-control study. Vital signs were monitorized prior to infection in newborns
      that had healthcare-associated blood stream infection (BSI). Maximum and minimum
      values of the vital signs (blood pressure, heart rate, respiratory rate and
      temperature) of the babies at rest were recorded from the nurse observation
      charts five days prior to clinical sepsis and compared with vital signs of
      healthy, age-matched babies. RESULTS: Maximum mean heart rates, respiratory rates
      and systolic blood pressure levels of the patients in BSI group were
      significantly higher than the control group in the past three days prior to
      clinical deterioration. CONCLUSION: Monitoring vital signs closely might be
      helpful in a newborn infant to define a BSI. In future, a respiratory and blood
      pressure predictive monitoring system such as heart rate variability index may be
      developed for newborn patients with sepsis.

PMID- 25367557
TI  - Antenatal corticosteroids and perinatal outcomes in infants born at 23-25 weeks
      of gestation.
AB  - OBJECTIVES: To evaluate the perinatal results of infants born between 23 and 25.6
      weeks of gestation. METHODS: Medical charts of all women giving birth prematurely
      (23-25.6 w) from January 2005 to December 2011 were retrospectively reviewed.
      Cases of malformed infants or deliveries elsewhere were excluded. RESULTS: 198
      infants were included. Chorioamnionitis occurred in 86 (43.4%) of the whole
      group: 26 (86.7%) in the 23-week; 35 (53.8%) in the 24-week and 25 (24.3%) in the
      25-week groups. Foetal maturation with antenatal corticosteroids was complete in
      119 cases (60.1%): 4 (13.3%) in the 23-week; 35 (53.8%) in the 24-week and 80
      (77.7%) in the 25-week groups. Foetal death at birth occurred in 22 cases (11%)
      and 61 newborns (30.8%) died in the neonatal period. Of the 106 survivors with 2
      years complete follow-up, 45 infants (42.4%) did not present sequelae; 16 infants
      (15.1%) had severe sequelae. A 66.6% (4) of infants born at 23 weeks of gestation
      did not present sequelae compared with a 32.3% (11) at 24 weeks and 45.4% (30) at
      25 weeks. CONCLUSIONS: The chorioamnionitis rate was higher when gestational age
      was lower. The foetal maturation rate was higher when gestational age was higher.
      A low severe sequelae rate was observed in the whole series, particularly in the
      23-week group where the rate was lower than expected; however, these results
      could have been influenced by the small size of the 23-week group.

PMID- 25367558
TI  - Treatment of Infantile Hemangioma in Regional Hospitals With eHealth Support:
      Evaluation of Feasibility and Acceptance by Parents and Doctors.
AB  - BACKGROUND: Since beta blockers became the preferred treatment for infantile
      hemangiomas (IH), the number of patients eligible for treatment is increasing.
      Currently treatment of IH with beta blockers is mainly reserved for expert
      centers, where wait times are lengthening. This demonstrated the need for
      development of a more efficient and accessible way of providing care for children
      needing treatment for IH. An eHealth intervention, Hemangioma Treatment Plan
      (HTP), was developed to treat IH in regional hospitals with online support from
      an academic doctor. OBJECTIVE: Our goal was to evaluate the feasibility of the
      eHealth intervention by determining its use, acceptance, and usability. By
      evaluating the feasibility, usage can be predicted and points for improvement can
      be defined, thereby facilitating implementation of the intervention. METHODS:
      Parents of children with an IH, presenting between October 2012 and November 2013
      at the tertiary expert Center for Congenital Vascular Anomalies Utrecht,
      requiring treatment with a beta blocker, were asked to participate in the digital
      HTP. Both parents and regional doctors were sent a study questionnaire.
      Acceptance and usability of the HTP were evaluated by using the modified
      Technology Acceptance Model. RESULTS: A total of 31 parents and 22 regional
      doctors participated in the eHealth intervention and received the questionnaire,
      and 25 parents and 15 doctors responded (response rates respectively 81% and
      68%). A majority of the parents (96%, 24/25) and the regional doctors (87%,
      13/15) considered the eHealth intervention useful in the care for IH. Most
      parents (76%, 19/25) and over half of the regional doctors (53%, 8/15) found the
      HTP easy to use. Technical problems using the HTP were reported by 28% (7/25) of
      the parents and 73% (11/15) of the doctors. The majority of parents (92%, 23/25)
      felt positive about usage of the HTP during treatment of their child. All
      regional doctors (100%, 15/15) felt positive about transition of treatment from
      the tertiary expert center to them, and 93% (14/15) felt positive about using the
      HTP. CONCLUSIONS: Our eHealth intervention shows good feasibility, especially
      among parents. Improvement with respect to technical problems, training of
      regional doctors, and achieving organizational support might be needed for
      successful implementation in the future.

PMID- 25367559
TI  - An in situ generated achiral Cu(II)-containing polymer complex sensor for
      enantioselective recognition induced from L-/D-histidine enantiomers.
AB  - A novel achiral polymer P-1 is synthesized by the polymerization of (2,5
      bis(octyloxy)-1,4-phenylene)diboronic acid (M-1) with pyridine-2,6
      diylbis(methanylylidene)bis(4-iodoaniline) (M-2) via Pd-catalyzed Suzuki coupling
      reaction. The tridentate ligand in the main chain backbone can further coordinate
      with Cu(2+) to afford the corresponding achiral copper-containing polymer complex
      P-2, which selectively responds to L-/D-histidine with significant fluorescence
      enhancement over other amino acids. Interestingly, P-2 exhibits obvious CD
      response toward L- or D-histidine compared with its model compound MC, indicating
      that this kind Cu(II)-containing polymer complex sensor can be used as an
      effective chemosensor for enantioselective recognition of histidine enantiomers
      by means of CD spectroscopy.

PMID- 25367561
TI  - Latent inhibition and facilitation of conditioned taste aversion in preweanling
      rats.
AB  - Early in ontogeny, taste preexposure has been found to induce latent inhibition
      as well as produce a facilitation of conditioned taste aversion (CTA). In this
      study, the effect of taste preexposure on CTA was investigated in 13-14 day old
      rats as a function of taste preexposure (0, 1, or 3 trials) and unconditioned
      stimulus intensity (LiCl: 0, 0.15, or 0.30 M). After one conditioning trial, with
      the low intensity US, an aversion was only observed after taste preexposure
      (facilitation). When using the strong US, an aversion was found without
      preexposure while latent inhibition was observed with 3 preexposure trials. In
      conclusion, stimulus preexposure can either facilitate conditioning or produce
      latent inhibition in infant rats, depending on the amount of stimulus preexposure
      and the intensity of the US.

PMID- 25367560
TI  - Study, by use of coarse-grained models, of the functionally crucial residues and
      allosteric pathway of anesthetic regulation of the Gloeobacter violaceus ligand
      gated ion channel.
AB  - Although pentameric ligand-gated ion channels (pLGICs) have been found to be the
      targets of general anesthetics, the mechanism of the effects of anesthetics on
      pLGICs remains elusive. pLGICs from Gloeobacter violaceus (GLIC) can be inhibited
      by the anesthetic ketamine. X-ray crystallography has shown that the ketamine
      binding site is distant from the channel gate of the GLIC. It is still not clear
      how ketamine controls the function of the GLIC by long-range allosteric
      regulation. In this work, the functionally crucial residues and allosteric
      pathway of anesthetic regulation of the GLIC were identified by use of a coarse
      grained thermodynamic method developed by our group. In our method, the
      functionally crucial sites were identified as the residues thermodynamically
      coupled with binding of ketamine. The results from calculation were highly
      consistent with experimental data. Our study aids understanding of the mechanism
      of the anesthetic action of ketamine on the GLIC by long-range allosteric
      modulation. 

PMID- 25367562
TI  - New cyclopeptide alkaloid and lignan glycoside from Justicia procumbens.
AB  - This study reported a new cyclopeptide alkaloid, justicianene A (1), and a new
      lignan glycoside, procumbenoside H (2), isolated from Justicia procumbens. The
      structures of the new compounds were elucidated by means of spectroscopic
      analysis, including extensive 2D NMR studies and mass spectrometry. Cyclopeptide
      alkaloids were first observed from the genus Justicia. Compound 2 was cytotoxic
      against human LoVo colon carcinoma cells with an IC50 value of 17.908 +/- 1.949
      MUM. 

PMID- 25367563
TI  - Thinking inside the box: endogenous alpha-anomeric lipid antigens.
AB  - The most powerful iNKT cell antigen is alpha-galactosylceramide (alpha-GalCer),
      derived from the marine sponge. However, alpha-anomeric glycolipids are thought
      to be absent in mammals. In this issue of Immunity, Kain et al., (2014)
      demonstrate the presence of mammalian alpha-linked glycosylceramides, such as
      alpha-GalCer.

PMID- 25367564
TI  - LOX-1 unlocks human plasma cell potential.
AB  - Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is best known for
      promoting atherosclerosis. In this issue of Immunity, Joo et al. (2014) find that
      dendritic cells triggered through LOX-1 can directly support plasmablast
      production via the production of the cytokines APRIL and BAFF.

PMID- 25367565
TI  - MicroRNAs in Tfh cells: micromanaging inflammaging.
AB  - MicroRNA (miR)-146a-deficient mice develop low-grade, chronic, and systemic
      inflammation, similar to inflammaging. Hu et al. (2014) demonstrate that the lack
      of miR-155 prevents the accumulation of Tfh cells and inflammaging in miR-146a
      deficient mice. They identify Fosl2 as a functionally important target of miR-155
      in Tfh cells.

PMID- 25367566
TI  - Complement and IL-22: partnering up for border patrol.
AB  - Intestinal pathobionts that escape into the periphery can cause serious morbidity
      and death. In this issue of Immunity, Hasegawa et al. (2014) show that the host's
      protective measures against such events include interleukin-22-driven systemic
      elimination of pathobionts via complement regulation.

PMID- 25367567
TI  - CD4 helpers put tissue-resident memory cells in their place.
AB  - The regulation of tissue-resident memory cell development is poorly understood.
      In this issue of Immunity, Laidlaw et al. (2014) demonstrate that CD4(+) T cells
      promote development of lung-resident memory cells by limiting T-bet expression
      and directing CD8(+) T cells to the airway epithelium.

PMID- 25367568
TI  - New hope in the search for Ebola virus treatments.
AB  - Because of its lethality, the Ebola virus often appears to be an invincible
      adversary. In Nature, Qiu et al. (2014) recently described the complete
      protection of nonhuman primates from deadly Ebola virus disease, even when
      treatment was begun as late as 5 days after infection.

PMID- 25367570
TI  - T follicular helper cell differentiation, function, and roles in disease.
AB  - Follicular helper T (Tfh) cells are specialized providers of T cell help to B
      cells, and are essential for germinal center formation, affinity maturation, and
      the development of most high-affinity antibodies and memory B cells. Tfh cell
      differentiation is a multistage, multifactorial process involving B cell lymphoma
      6 (Bcl6) and other transcription factors. This article reviews understanding of
      Tfh cell biology, including their differentiation, migration, transcriptional
      regulation, and B cell help functions. Tfh cells are critical components of many
      protective immune responses against pathogens. As such, there is strong interest
      in harnessing Tfh cells to improve vaccination strategies. Tfh cells also have
      roles in a range of other diseases, particularly autoimmune diseases. Overall,
      there have been dramatic advances in this young field, but there is much to be
      learned about Tfh cell biology in the interest of applying that knowledge to
      biomedical needs.

PMID- 25367571
TI  - The identification of the endogenous ligands of natural killer T cells reveals
      the presence of mammalian alpha-linked glycosylceramides.
AB  - Glycosylceramides in mammalian species are thought to be present in the form of
      beta-anomers. This conclusion was reinforced by the identification of only one
      glucosylceramide and one galactosylceramide synthase, both beta-transferases, in
      mammalian genomes. Thus, the possibility that small amounts of alpha-anomers
      could be produced by an alternative enzymatic pathway, by an unfaithful enzyme,
      or spontaneously in unusual cellular compartments has not been examined in
      detail. We approached the question by taking advantage of the exquisite
      specificity of T and B lymphocytes and combined it with the specificity of
      catabolic enzymes of the sphingolipid pathway. Here, we demonstrate that
      mammalian immune cells produce constitutively very small quantities of alpha
      glycosylceramides, which are the major endogenous ligands of natural killer T
      cells. Catabolic enzymes of the ceramide and glycolipid pathway tightly control
      the amount of these alpha-glycosylceramides. The exploitation of this pathway to
      manipulate the immune response will create new therapeutic opportunities.

PMID- 25367569
TI  - HIF transcription factors, inflammation, and immunity.
AB  - The hypoxic response in cells and tissues is mediated by the family of hypoxia
      inducible factor (HIF) transcription factors; these play an integral role in the
      metabolic changes that drive cellular adaptation to low oxygen availability. HIF
      expression and stabilization in immune cells can be triggered by hypoxia, but
      also by other factors associated with pathological stress: e.g., inflammation,
      infectious microorganisms, and cancer. HIF induces a number of aspects of host
      immune function, from boosting phagocyte microbicidal capacity to driving T cell
      differentiation and cytotoxic activity. Cellular metabolism is emerging as a key
      regulator of immunity, and it constitutes another layer of fine-tuned immune
      control by HIF that can dictate myeloid cell and lymphocyte development, fate,
      and function. Here we discuss how oxygen sensing in the immune microenvironment
      shapes immunological response and examine how HIF and the hypoxia pathway control
      innate and adaptive immunity.

PMID- 25367572
TI  - The oncoprotein and transcriptional regulator Bcl-3 governs plasticity and
      pathogenicity of autoimmune T cells.
AB  - Bcl-3 is an atypical member of the IkappaB family that modulates transcription in
      the nucleus via association with p50 (NF-kappaB1) or p52 (NF-kappaB2) homodimers.
      Despite evidence attesting to the overall physiologic importance of Bcl-3, little
      is known about its cell-specific functions or mechanisms. Here we demonstrate a T
      cell-intrinsic function of Bcl-3 in autoimmunity. Bcl-3-deficient T cells failed
      to induce disease in T cell transfer-induced colitis and experimental autoimmune
      encephalomyelitis. The protection against disease correlated with a decrease in
      Th1 cells that produced the cytokines IFN-gamma and GM-CSF and an increase in
      Th17 cells. Although differentiation into Th1 cells was not impaired in the
      absence of Bcl-3, differentiated Th1 cells converted to less-pathogenic Th17-like
      cells, in part via mechanisms involving expression of the RORgammat transcription
      factor. Thus, Bcl-3 constrained Th1 cell plasticity and promoted pathogenicity by
      blocking conversion to Th17-like cells, revealing a unique type of regulation
      that shapes adaptive immunity.

PMID- 25367573
TI  - The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and
      tissue repair.
AB  - Programmed necrosis or necroptosis is an inflammatory form of cell death that
      critically requires the receptor-interacting protein kinase 3 (RIPK3). Here we
      showed that RIPK3 controls a separate, necrosis-independent pathway of
      inflammation by regulating cytokine expression in dendritic cells (DCs). Ripk3(-/
      ) bone-marrow-derived dendritic cells (BMDCs) were highly defective in
      lipopolysaccharide (LPS)-induced expression of inflammatory cytokines. These
      effects were caused by impaired NF-kappaB subunit RelB and p50 activation and by
      impaired caspase 1-mediated processing of interleukin-1beta (IL-1beta). This DC
      specific function of RIPK3 was critical for injury-induced inflammation and
      tissue repair in response to dextran sodium sulfate (DSS). Ripk3(-/-) mice
      exhibited an impaired axis of injury-induced IL-1beta, IL-23, and IL-22 cytokine
      cascade, which was partially corrected by adoptive transfer of wild-type DCs, but
      not Ripk3(-/-) DCs. These results reveal an unexpected function of RIPK3 in NF
      kappaB activation, DC biology, innate inflammatory-cytokine expression, and
      injury-induced tissue repair.

PMID- 25367575
TI  - Interleukin-22 regulates the complement system to promote resistance against
      pathobionts after pathogen-induced intestinal damage.
AB  - Pathobionts play a critical role in disease development, but the immune
      mechanisms against pathobionts remain poorly understood. Here, we report a
      critical role for interleukin-22 (IL-22) in systemic protection against bacterial
      pathobionts that translocate into the circulation after infection with the
      pathogen Clostridium difficile. Infection with C. difficile induced IL-22, and
      infected Il22(-/-) mice harbored high numbers of pathobionts in extraintestinal
      organs despite comparable pathogen load and intestinal damage in mutant and wild
      type mice. Pathobionts exhibited increased resistant against complement-mediated
      phagocytosis, and their intravenous administration resulted in high animal
      mortality. Selective removal of translocated commensals rescued Il22(-/-) mice,
      and IL-22 administration enhanced the elimination of pathobionts.
      Mechanistically, IL-22 augmented bacterial phagocytosis by increasing the
      expression and bacterial binding of complement C3. Our study demonstrates an
      unexpected role for IL-22 in controlling the elimination of pathobionts that
      enter the systemic circulation through the regulation of the complement system.

PMID- 25367574
TI  - miR-155 promotes T follicular helper cell accumulation during chronic, low-grade
      inflammation.
AB  - Chronic inflammation is a contributing factor to most life-shortening human
      diseases. However, the molecular and cellular mechanisms that sustain chronic
      inflammatory responses remain poorly understood, making it difficult to treat
      this deleterious condition. Using a mouse model of age-dependent inflammation
      that results from a deficiency in miR-146a, we demonstrate that miR-155
      contributed to the progressive inflammatory disease that emerged as Mir146a(-/-)
      mice grew older. Upon analyzing lymphocytes from inflamed versus healthy middle
      aged mice, we found elevated numbers of T follicular helper (Tfh) cells, germinal
      center (GC) B cells, and autoantibodies, all occurring in a miR-155-dependent
      manner. Further, Cd4-cre Mir155(fl/fl) mice were generated and demonstrated that
      miR-155 functions in T cells, in addition to its established role in B cells, to
      promote humoral immunity in a variety of contexts. Taken together, our study
      discovers that miR-146a and miR-155 counterregulate Tfh cell development that
      drives aberrant GC reactions during chronic inflammation.

PMID- 25367576
TI  - TRAIL+ NK cells control CD4+ T cell responses during chronic viral infection to
      limit autoimmunity.
AB  - Natural killer (NK) cells have been reported to control adaptive immune responses
      that occur in lymphoid organs at the early stages of immune challenge. The
      physiological purpose of such regulatory activity remains unclear, because it
      generally does not confer a survival advantage. We found that NK cells
      specifically eliminated activated CD4(+) T cells in the salivary gland during
      chronic murine cytomegalovirus (MCMV) infection. This was dependent on TNF
      related apoptosis inducing ligand (TRAIL) expression by NK cells. Although NK
      cell-mediated deletion of CD4(+) T cells prolonged the chronicity of infection,
      it also constrained viral-induced autoimmunity. In the absence of this activity,
      chronic infection was associated with a Sjogren's-like syndrome characterized by
      focal lymphocytic infiltration into the glands, production of autoantibodies, and
      reduced saliva and tear secretion. Thus, NK cells are an important homeostatic
      control that balances the efficacy of adaptive immune responses with the risk of
      developing autoimmunity.

PMID- 25367578
TI  - Effects of developmental change in body size on ectotherm body temperature and
      behavioral thermoregulation: caterpillars in a heat-stressed environment.
AB  - Ectotherms increase in size dramatically during development, and this growth
      should have substantial effects on their body temperature and ability to
      thermoregulate. To better understand how this change in size affects temperature,
      we examined the direct effects of body size on body temperature in Battus
      philenor caterpillars, and also how body size affects both the expression and
      effectiveness of thermal refuge-seeking, a thermoregulatory behavior. Field
      studies of both live caterpillars and physical operative temperature models
      indicated that caterpillar body temperature increases with body size. The
      operative temperature models also showed that thermal refuges have a greater
      cooling effect for larger caterpillars, while a laboratory study found that
      larger caterpillars seek refuges at a lower temperature. Although the details may
      vary, similar connections between developmental growth, temperature, and
      thermoregulation should be common among ectotherms and greatly affect both their
      development and thermal ecology. 

PMID- 25367577
TI  - A minor subset of Batf3-dependent antigen-presenting cells in islets of
      Langerhans is essential for the development of autoimmune diabetes.
AB  - Autoimmune diabetes is characterized by inflammatory infiltration; however, the
      initiating events are poorly understood. We found that the islets of Langerhans
      in young nonobese diabetic (NOD) mice contained two antigen-presenting cell (APC)
      populations: a major macrophage and a minor CD103(+) dendritic cell (DC)
      population. By 4 weeks of age, CD4(+) T cells entered islets coincident with an
      increase in CD103(+) DCs. In order to examine the role of the CD103(+) DCs in
      diabetes, we examined Batf3-deficient NOD mice that lacked the CD103(+) DCs in
      islets and pancreatic lymph nodes. This led to a lack of autoreactive T cells in
      islets and, importantly, no incidence of diabetes. Additional examination
      revealed that presentation of major histocompatibility complex (MHC) class I
      epitopes in the pancreatic lymph nodes was absent with a partial impairment of
      MHC class II presentation. Altogether, this study reveals that CD103(+) DCs are
      essential for autoimmune diabetes development.

PMID- 25367579
TI  - The effect of direct interspecific competition on patch exploitation strategies
      in parasitoid wasps.
AB  - The presence of competitors may affect the pay-off of individuals' foraging
      strategies. They should therefore modify their resource exploitation decisions
      accordingly. In such a direct competition situation, theory predicts that
      individuals should stay longer on a resource patch than when foraging alone.
      However, models predicting patch residence time focus on intraspecific
      competition without agonistic interactions. Here, we investigate the patch use
      strategies of females of two parasitoid species, Eupelmus vuilleti and Dinarmus
      basalis, attacking the same host, Callosobruchus maculatus, knowing that D.
      basalis is more aggressive and can exclude E. vuilleti during pairwise contests
      for single hosts. Our results showed that time allocation and oviposition
      strategies differed in relation to the species and type of competition (i.e.,
      presence/absence of competitor, simultaneous/sequential female introduction or
      resident/intruder female). Eupelmus vuilleti females tended to wait in the patch
      surroundings for D. basalis females' departure to return and exploit hosts
      parasitized by the opponent (after destruction of her eggs). In contrast, D.
      basalis females tended to self-superparasitize and stay motionless near the
      hosts. After detecting an E. vuilleti female entering the patch, they attacked
      and chased her permanently from the patch. Females of both species spent less
      time in the patch when faced with a competitor than when alone. This study is the
      first to test the influence of direct interspecific competition and arrival order
      on patch exploitation strategies in parasitoid species, and highlights the
      necessity to include agonistic behaviors in theoretical models predicting optimal
      patch residence time in competitive situations. 

PMID- 25367580
TI  - Surgical management of primary hyperparathyroidism in Canada.
AB  - Primary hyperparathyroisim is a relatively common condition, for which the
      standard treatment is surgical excision of one or more of the parathyroid glands.
      Primary hyperparathyroidism can be due to a single adenoma or multiple gland
      hyperplasia. In recent decades localizing imaging has improved and there has been
      a shift away from multiple gland exploration toward a single gland excision.
      There are, however, no practice guidelines regarding an optimal approach to this
      condition. This study shows that there is a high degree of variation in practices
      across Canada and a large amount of uncertainty in the approach to primary
      hyperparathyroidism.

PMID- 25367581
TI  - Surgical management of combined intramedullary arteriovenous malformation and
      perimedullary arteriovenous fistula within the hybrid operating room after five
      years of performing focus fractionated radiotherapy: case report.
AB  - Perimedullary arteriovenous fistula (AVF) shunts occur on the spinal cord surface
      and can be treated surgically or by endovascular embolization. In contrast, the
      nidus of an intramedullary arteriovenous malformation (AVM) is located in the
      spinal cord and is difficult to treat surgically or by endovascular techniques.
      The benefits of radiotherapy for treating intramedullary AVM have been published,
      but are anecdotal and consist largely of case reports. We present a case of
      combined cervical intramedullary AVM and perimedullary AVF which received
      surgical treatment within a hybrid operating room (OR) after 5 years of focus
      fractionated radiotherapy. A 37-year-old male presented with stepwise worsening
      myelopathy. Magnetic resonance imaging and spinal angiography revealed
      intramedullary AVM and perimedullary AVF at the C3 to C5 levels. In order to
      reduce nidus size and blood flow, we first performed focal fractionated
      radiotherapy. Five years later, the lesion volume was reduced. Following this,
      direct surgery was performed by an anterior approach using corpectomy in the
      hybrid OR. The spinal cord was monitored by motor-evoked potential throughout the
      surgery. Complete obliteration of the fistulous connection was confirmed by
      intraoperative indocyanine green video-angiography and intraoperative
      angiography, preserving the anterior spinal artery. We conclude that surgical
      treatment following focal fractionated radiotherapy may become one strategy for
      patients who are initially deemed ineligible for endovascular embolization and
      surgical treatment. Furthermore, the hybrid OR enables safe and precise treatment
      for spinal vascular disorders in the fields of endovascular treatment and
      neurosurgery. 

PMID- 25367582
TI  - Neurovascular bundle decompression without excessive dissection for tarsal tunnel
      syndrome.
AB  - Tarsal tunnel syndrome (TTS) is an entrapment neuropathy of the posterior tibial
      nerve and its branches in the tarsal tunnel. We present our less invasive
      surgical treatment of TTS in 69 patients (116 feet) and their clinical outcomes.
      The mean follow-up period was 64.6 months. With the patient under local
      anesthesia we use a microscope to perform sharp dissection of the flexor
      retinaculum and remove the connective tissues surrounding the posterior tibial
      nerve and vessels. To prevent postoperative adhesion and delayed neuropathy,
      decompression is performed to achieve symptom improvement without excessive
      dissection. Decompression is considered complete when the patient reports
      intraoperative symptom abatement and arterial pulsation is sufficient. The
      sensation of numbness and/or pain and of foreign substance adhesion was reduced
      in 92% and 95% of our patients, respectively. In self-assessments, 47 patients
      (68%) reported the treatment outcome as satisfactory, 15 (22%) as acceptable, and
      7 (10%) were dissatisfied. Of 116 feet, 4 (3%) required re-operation, initial
      decompression was insufficient in 2 feet and further decompression was performed;
      in the other 2 feet improvement was achieved by decompression of the distal
      tarsal tunnel. Our surgical method involves neurovascular bundle decompression to
      obtain sufficient arterial pulsation. As we use local anesthesia, we can confirm
      symptom improvement intraoperatively, thereby avoiding unnecessary excessive
      dissection. Our method is simple, safe, and without detailed nerve dissection and
      it prevents postoperative adhesion. 

PMID- 25367583
TI  - Surgical management of solitary nerve sheath tumors of the cervical spine: a
      retrospective case analysis based on tumor location and extension.
AB  - Complete resection of spinal nerve sheath tumors (NSTs) does not always result in
      significant neurological deficit. The purpose of this retrospective case analysis
      was to discuss the optimal surgical strategy for spinal NST of the cervical
      spine. Twenty-four patients who underwent surgery for solitary cervical NST over
      the past decade were included in this retrospective study. Patients with
      neurofibromatosis or schwannomatosis were excluded. Seventeen of the 24 cases
      (70.8%) showed extradural dumbbell extension, most frequently at the C1 or C2
      vertebral level. Neurological condition was assessed using the modified McCormick
      functional schema and sensory pain scale. Total removal of the tumor was achieved
      in 20 of 24 cases (83.3%). Staged surgery using combined anterior and posterior
      approaches was applied for 2 of 17 cases with extradural dumbbell extension.
      Tumor involvement with nerve root fibers critical for upper extremity function
      (C5-C8) was recognized in 6 of 24 cases (25.0%), with complete resection in all 6
      cases. Final assessment of neurological function revealed satisfactory or
      acceptable recovery in all 6 patients. Spinal NSTs with extradural dumbbell
      extension are a common condition in the cervical spine. Complete removal of
      spinal NST of the cervical spine may carry a risk of permanent neurological
      deficit, but such sequelae appeared to be the exception in the present case
      analysis. A radical and safe surgical strategy, including staged surgery
      combining anterior and posterior approaches, should be tailored to the individual
      case. 

PMID- 25367584
TI  - Surgical management of traumatic acute subdural hematoma in adults: a review.
AB  - Traumatic acute subdural hematoma (ASDH) is a major clinical entity in traumatic
      brain injury (TBI). It acts as a space occupying lesion to increase intracranial
      pressure, and is often complicated by co-existing lesions, and is modified by
      cerebral blood flow (CBF) changes, coagulopathy, and delayed hematomas. Because
      of its complicated pathophysiology, the mortality of ASDH is still remaining
      high. In this review article, its epidemiology, pathophyiology, surgical
      treatment, and salvage ability are described. With regard to epidemiology, as the
      population ages, growing number of elderly patients with ASDH, especially
      patients with prehospital anticoagulant and antiplatelets, increase. Concerning
      pathophysiology, in addition to well-known initial intracranial hypertension and
      subsequent ischemia, delayed hyperemia/hyperperfusion, or delayed hematoma is
      being recognized frequently in recent years. However, optimal treatments for
      these delayed phenomenons have not been established yet. With regard to surgical
      procedures, all of craniotomy, decompressive craniectomy, and initial
      trephination strategies seem to be effective, but superiority of each procedure
      have not been established yet. Since Glasgow Coma Scale (GCS) scores, age,
      papillary reaction, and computed tomographic findings are strongly correlated to
      outcome, each factor has been investigated as an indicator of salvage ability.
      None of them, however, has been defined as such one. In future studies,
      epidemiological changes as population ages, management of delayed
      pathophysiology, superiority of each surgical procedures, and salvage ability
      should be addressed. 

PMID- 25367585
TI  - Cavernous angiomas of the cauda equina: clinical characteristics and surgical
      outcomes.
AB  - Cavernous angioma (CA) is a rare hamartomatous vascular lesion, consisting of
      abnormal, dilated, and packed sinusoidal vascular channels without interposed
      nervous tissue. CAs of the cauda equina are exceedingly rare and have been
      previously reported in the literature as case reports. The aim of this study was
      to discuss the clinical presentation and the outcomes of microsurgery for these
      rare lesions. We retrospectively reviewed the records of 10 patients who
      underwent microsurgery for CAs of the cauda equina. All patients had performed
      pre- and postoperative magnetic resonance imaging (MRI). CAs of the cauda equina
      generally exhibited mixed intensity on T1- and T2-weighted images. Contrast
      enhanced T1-weighted images showed heterogeneous enhancement. The hemosiderin
      ring which surrounded the cauda equina CA was rare. Gross total resection was
      achieved in all cases. All patients were followed up, with a mean duration of
      41.1 months. Long-term neurological function was improved in nine patients and
      remained stable in one patient. No recurrence was observed on MRI. CAs should be
      considered in the differential diagnosis of cauda equina tumors. Because of the
      excessive vascularity of CAs, en bloc resection is recommended. For symptomatic
      patients, early surgery should be performed before neurological deficits
      deteriorate. 

PMID- 25367586
TI  - Experimental study on the viscosity and adhesive performance of exogenous liquid
      fibrin glue.
AB  - Exogenous fibrin glue (FG) is highly suitable for neurosurgical procedures,
      because of its viscosity and adhesive properties. Several FGs are commercially
      available, but only few reports detail their differences. In the present study,
      we investigated the viscosity and adhesive performance of two types of FG: one is
      derived from blood donated in Europe and the United States (CSL Behring's
      Beriplast((r)), BP) and the other is derived from blood donated in Japan (the
      Chemo-Sero-Therapeutic Research Institute's Bolheal((r)), BH). The viscosity test
      that measured fibrinogen viscosity revealed that BP had significantly higher
      viscosity than BH. Similarly, the dripping test showed that BP traveled a
      significantly shorter drip distance in the vertical direction than BH, although
      the transverse diameter of the coagulated FG did not differ statistically
      significantly. In the tensile strength test, BP showed superior adhesion
      performance over BH. The histological study of the hematoxylin-eosin-stained
      specimens in both groups showed favorable adhesion. Although further studies are
      required on its manufacturing and usage methods, FG shows differences in
      viscosity and adhesive performance according to the blood from which it is
      derived. We conclude that it is desirable to select the type and usage method of
      FG according to the characteristics of the surgical operation in question. Our
      findings suggest that FG produced from the blood donated in Europe and the United
      States might be more suitable for use in surgical procedures that demand an
      especially high degree of viscosity and rapid adhesive performance. 

PMID- 25367587
TI  - Update on intensive neuromonitoring for patients with traumatic brain injury: a
      review of the literature and the current situation.
AB  - Intracranial pressure (ICP) measurements are fundamental in the present protocols
      for intensive care of patients during the acute stage of severe traumatic brain
      injury. However, the latest report of a large scale randomized clinical trial
      indicated no association of ICP monitoring with any significant improvement in
      neurological outcome in severely head injured patients. Aggressive treatment of
      patients with therapeutic hypothermia during the acute stage of traumatic brain
      injury also failed to show any significant beneficial effects on clinical
      outcome. This lack of significant results in clinical trials has limited the
      therapeutic strategies available for treatment of severe traumatic brain injury.
      However, combined application of different types of neuromonitoring, including
      ICP measurement, may have potential benefits for understanding the
      pathophysiology of damaged brains. The combination of monitoring techniques is
      expected to increase the precision of the data and aid in prevention of secondary
      brain damage, as well as assist in determining appropriate time periods for
      therapeutic interventions. In this study, we have characterized the techniques
      used to monitor patients during the acute severe traumatic brain injury stage, in
      order to establish the beneficial effects on outcome observed in clinical studies
      conducted in the past and to follow up any valuable clues that point to
      additional strategies for aggressive management of these patients. 

PMID- 25367588
TI  - Current topics in sports-related head injuries: a review.
AB  - We review the current topic in sports-related head injuries including acute
      subdural hematoma (ASDH), concussion, and chronic traumatic encephalopathy (CTE).
      Sports-related ASDH is a leading cause of death and severe morbidity in popular
      contact sports like American football in the USA and judo in Japan. It is thought
      that rotational acceleration is most likely to produce not only cerebral
      concussion but also ASDH due to the rupture of a parasagittal bridging vein,
      depending on the severity of the rotational acceleration injury. Repeated sports
      head injuries increase the risk for future concussion, cerebral swelling, ASDH or
      CTE. To avoid fatal consequences or CTE resulting from repeated concussions, an
      understanding of the criteria for a safe post-concussion return to play (RTP) is
      essential. Once diagnosed with a concussion, the athlete must not be allowed to
      RTP the same day and should not resume play before the concussion symptoms have
      completely resolved. If brain damage has been confirmed or a subdural hematoma is
      present, the athlete should not be allowed to participate in any contact sports.
      As much remains unknown regarding the pathogenesis and pathophysiology of sports
      related concussion, ASDH, and CTE, basic and clinical studies are necessary to
      elucidate the crucial issues in sports-related head injuries. 

PMID- 25367590
TI  - Infusions of artichoke and milk thistle represent a good source of phenolic acids
      and flavonoids.
AB  - Cynara scolymus L. (artichoke) and Silybum marianum (L.) Gaertn (milk thistle)
      are two herbs well-known for their efficiency in the prevention/treatment of
      liver injuries, among other chronic diseases. Therefore, the aim of this work was
      to characterize specific bioactive components, phenolic compounds, in
      hydromethanolic extracts but also in infusions (the most commonly used
      preparations) obtained from the whole plant of milk thistle and artichoke. The
      phenolic profiles were accessed using HPLC-DAD-MS/ESI. Infusions of both species
      presented higher phenolic contents than the hydromethanolic extracts. Milk
      thistle presented a similar phenolic composition between the two preparations,
      revealing only differences in the quantities obtained. Nevertheless, artichoke
      revealed a slightly different profile considering infusion and hydromethanolic
      extracts. Apigenin-7-O-glucuronide was the major flavonoid found in milk thistle,
      while luteolin-7-O-glucuronide was the most abundant in artichoke. Therefore,
      infusions of both artichoke and milk thistle represent a good source of bioactive
      compounds, especially phenolic acids and flavonoids. 

PMID- 25367589
TI  - Recent advances and future directions of hypothermia therapy for traumatic brain
      injury.
AB  - For severe traumatic brain injury (TBI) patients, no effective treatment method
      replacing hypothermia therapy has emerged, and hypothermia therapy still plays
      the major role. To increase its efficacy, first, early introduction is important.
      Since there are diverse pathologies of severe TBI, it is necessary to
      appropriately control the temperature in the hypothermia maintenance and
      rewarming phases by monitoring relative to the pathology. Currently, hypothermia
      is considered appropriate for severe TBI patients requiring craniotomy for
      removal of hematoma, while induced normothermia is appropriate for severe TBI
      patients with diffuse brain injury. Induced normothermia is expected to exhibit a
      cerebroprotective effect equivalent to hypothermia, as well as reduce the
      complexity of whole-body management and systemic complications. According to the
      Japan Neurotrauma Data Bank of the Japan Society of Neurotraumatology, the brain
      temperature was controlled in 43.9% of severe TBI patients (induced normothermia:
      32.2%, hypothermia: 11.7%) in Japan. Brain temperature management was performed
      mainly in young patients, and the outcome on discharge was favorable in patients
      who received brain temperature management. Particularly, patients who need
      craniotomy for removal of hematoma were a good indication of therapeutic
      hypothermia. Improvement of therapeutic outcomes with widespread temperature
      management in TBI patients is expected. 

PMID- 25367591
TI  - Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with
      therapeutic hypothermia: a retrospective case-control study.
AB  - BACKGROUND: Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for
      coagulopathy due to systemic oxygen deprivation. Additionally, therapeutic
      hypothermia (TH) slows enzymatic activity of the coagulation cascade, leading to
      constitutive prolongation of routinely assessed coagulation studies. The level of
      laboratory abnormality that predicts bleeding is unclear, leading to varying
      transfusion therapy practices. METHODS: HIE infants treated with TH between 2008
      2012 were included in this retrospective study. Initial, minimum (min) and
      maximum (max) values of International Normalized Ratio (INR), activated partial
      thromboplastin time (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured
      twice daily during TH) were collected. Bleeding was defined as clinically
      significant if associated with 1) decreased hemoglobin (Hb) by 2 g/dL in 24
      hours, 2) transfusion of blood products for hemostasis, or 3) involvement of a
      critical organ system. Laboratory data between the bleeding group (BG) and non
      bleeding group (NBG) were compared. Variables that differed significantly between
      groups were evaluated with Receiver Operating Characteristic Curve (ROC) analyses
      to determine cut-points to predict bleeding. RESULTS: Laboratory and bleeding
      data were collected from a total of 76 HIE infants with a mean (+/-SD)
      birthweight of 3.34 +/- 0.67 kg and gestational age of 38.6 +/- 1.9 wks. BG
      included 41 infants. Bleeding sites were intracranial (n = 13), gastrointestinal
      (n = 19), pulmonary (n = 18), hematuria (n = 11) or other (n = 1). There were no
      differences between BG and NBG in baseline characteristics (p > 0.05). Both
      groups demonstrated INR and aPTT values beyond the acceptable reference ranges
      utilized for full tem newborns. BG had higher initial and max INR, initial aPTT,
      and lower min PLT and min Fib compared to NBG. ROC analyses revealed that
      platelet count <130 * 109/L, fib level <1.5 g/L, and INR >2 discriminated BG from
      NBG. CONCLUSIONS: Laboratory evidence of coagulopathy is universal in HIE babies
      undergoing TH. Transfusion strategies to maintain PLT counts >130 * 109/L, fib
      level >1.5 g/L, and INR <2 may prevent clinical bleeding in this high risk
      population.

PMID- 25367592
TI  - Reference ranges for shape indices of the flow-volume loop of healthy children.
AB  - BACKGROUND: The concavity of the descending limb of the maximum expiratory flow
      volume loop (MEFVL) is the earliest change associated with airflow obstruction in
      small airways (ATS/ERS Task Force). The shape of the MEFVL changes with age but
      there are no reference values for shape indices for preschool and school
      children. OBJECTIVES: To define pediatric reference values for spirometric data
      and 3 shape indices of MEFVL: 2 geometric indices: the beta angle i.e., the angle
      between the first 1/2 part and the 2nd part of the MEFVL and the forced
      expiratory flow after 50% of the forced vital capacity (FVC) has been
      exhaled/peak expiratory flow (FEF50 /PEF) ratio; and a ratio that describes
      relative growth between airway and lung parenchyma, the forced expiratory flow
      between 25 and 75% of FVC/FVC ratio (FEF25-75 /FVC ratio). METHODS: Data were
      obtained from 446 Caucasian children (2.5 to 15-year-old). The lambda, mu, sigma
      method was applied. RESULTS: References for spirometric parameters and 3 shape
      indices. The geometric indices decreased with age from 3 years of age (mean beta
      angle was 215 degrees  and FEF50 /PEF ratio was 0.82) until 8 years of age (mean
      beta angle was 191 degrees  and FEF50 /PEF ratio was 0.60) and then remained
      constant. The FEF25-75 /FVC ratio also decreased with age. Sex was a significant
      determinant for FEF25-75 /FVC ratio predicted values. CONCLUSIONS: This study
      provides standard reference equations for indices of mid-expiratory flows in
      children and we suggest using the FEF50 /PEF index.

PMID- 25367593
TI  - Microstructural analysis of three-dimensional canal network in the rabbit lumbar
      vertebral endplate.
AB  - Insufficient nutrient supply through vertebral canal structures to the
      intervertebral disc (IVD) has been considered as an important contributor for
      disc degeneration. Despite previous canal structure characterization studies
      using histology, scanning electron microscopy, and angiography, among others,
      their three-dimensional (3D) topology inside the vertebral endplate remains
      poorly understood. This study aims to characterize the 3D canal structure in the
      rabbit lumbar vertebral endplate using micro computed tomography (MUCT).
      Vertebral endplates were imaged using high-resolution MUCT with 1.4 * 1.4 * 1.8
      MUm voxel size. Diameter, length, orientation, and depth starting from the
      vertebral endplate surface were analyzed for each canal using individual 3D canal
      models from the vertebral endplate scans. In the layer underneath the vertebral
      endplate, at a mean depth of 76.2 MUm, longitudinally-oriented relatively short
      length (57.6 MUm) and small diameter (45.7 MUm) canals were dominant. Large-scale
      canals with a mean diameter of 152.1 MUm running parallel to the endplate surface
      were isolated at the depth of 224.1 MUm. These canals were connected to both IVD
      and bone marrow spaces through vertically oriented canals.

PMID- 25367594
TI  - The structural and energetic aspects of substrate binding and the mechanism of
      action of the DapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase
      (DapE) investigated using a hybrid QM/MM method.
AB  - With increasing cases of fatal bacterial infections and growing antibiotic
      resistance, unrelenting efforts are necessary for identification of novel
      antibiotic targets and new drug molecules. The dapE-encoded N-succinyl-L,L
      diaminopimelic acid desuccinylase (DapE) is a di-nuclear Zn containing enzyme in
      the lysine biosynthetic pathway which is indispensable for bacterial survival and
      absent in the human host, thus a potential antibiotic target. The DapE enzyme
      catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelic acid (SDAP) to give
      rise to succinic acid and L,L-diaminopimelic acid. The mechanism of action of the
      DapE catalyzed SDAP hydrolysis is investigated employing a hybrid QM/MM
      computational method. The DapE side chains, such as, Arg178, Thr325, Asn345, are
      found to play a role in substrate identification and stabilization of the enzyme
      active site. Furthermore, a glycine rich loop (Gly322-Ser326) is found to
      facilitate tight binding of the substrate in the enzyme active site. The
      catalytic reaction progresses via a general acid-base hydrolysis mechanism where
      Glu134 first acts as a Lewis base by activating the catalytic water molecule in
      the active site, followed by guiding the resulting hydroxyl ion for a
      nucleophilic attack on the substrate, and finally acts as a Lewis acid by
      donating a proton to the substrate. The intermediates and transition states along
      the reaction pathway have been structurally and energetically characterized. A
      conformational change in the side chain of Asp100, which bridges the two Zn
      centers of the enzyme, is observed which facilitates the enzymatic action by
      lowering the activation energy and leads to the formation of a new intermediate
      during the catalytic reaction. The nucleophilic attack is found to be the rate
      determining step.

PMID- 25367595
TI  - Effects of minority stress processes on the mental health of Latino men who have
      sex with men and women: a qualitative study.
AB  - Emerging literature on minority stress among sexual minority populations has
      described the negative consequences that multiple minority statuses may exert on
      mental health and well-being. This literature has tended to focus on individuals
      whose self-identifications reflect sexual minority sexual categories, such as gay
      or bisexual, and has explored the intersection of these definitions with ethnic,
      racial, and class statuses. Few such studies have explored mental health among
      men who actively deny a sexual minority sexual identity label while engaging in
      same-sex sexual behaviors. The present study used ethnographic interview data
      from 20 non-gay-identified bisexually behaving Dominican and Puerto Rican men in
      New York City. Participants described discovery of same sex sexual behavior as a
      threat to their intimate relationships, community affiliation, and counter to
      expectations of Latino masculinity. Recounting a wide range of information
      management strategies used to avoid open disclosure about their sexual lives,
      participants experienced the potential consequences of disclosure as extreme and
      even life threatening. Men anticipated social isolation, depression, self-injury,
      and suicidality as possible outcomes from disclosing sexual behavior with other
      men to their female romantic partners. This analysis provides direction for
      future research on minority stress processes and mental health service delivery
      among Latino men who have sex with men and women. 

PMID- 25367596
TI  - Long-Term Impact of Different Immunosuppressive Drugs on QT and PR Intervals in
      Renal Transplant Patients.
AB  - BACKGROUND: Sudden cardiac deaths due to arrhythmias are thought to be an
      important cause of mortality in patients with renal transplants. Exposure to
      immunosuppressive drugs may lead to QT or PR interval abnormalities which may
      consequently cause arrhythmias. Our study investigated the long term impact of
      four different immunosuppressive drugs on PR and corrected QT intervals (QTc) in
      renal transplant patients METHODS: The study population consisted of 98 kidney
      transplant recipients. Study patients were receiving immunosuppressive management
      with tacrolimus, cyclosporine A, everolimus or azathioprine according to the
      local protocols. QTc and PR intervals obtained from the most recent post
      transplant electrocardiograms were compared with the pre-transplant intervals
      dated before the transplantation procedure. RESULTS: Post-transplant QTc
      intervals had prolonged significantly in comparison to the pre-transplant QTc
      intervals in all groups. However, there were no significant differences between
      the immunosuppressive agents with regard to post-transplant QTc interval
      prolongation (p > 0.05). There were no significant differences between the groups
      with regard to the pre and post-transplant PR interval changes (p > 0.05).
      CONCLUSIONS: QT interval prolongation, a marker of risk for arrhythmias and
      sudden death, is highly prevalent among kidney transplant patients receiving
      different classes of immunosuppressive drugs.

PMID- 25367597
TI  - Exfoliated-SnS2 restacked on graphene as a high-capacity, high-rate, and long
      cycle life anode for sodium ion batteries.
AB  - Designed as a high-capacity, high-rate, and long-cycle life anode for sodium ion
      batteries, exfoliated-SnS2 restacked on graphene is prepared by the hydrolysis of
      lithiated SnS2 followed by a facile hydrothermal method. Structural and
      morphological characterizations demonstrate that ultrasmall SnS2 nanoplates (with
      a typical size of 20-50 nm) composed of 2-5 layers are homogeneously decorated on
      the surface of graphene, while the hybrid structure self-assembles into a three
      dimensional (3D) network architecture. The obtained SnS2/graphene nanocomposite
      delivers a remarkable capacity as high as 650 mA h g(-1) at a current density of
      200 mA g(-1). More impressively, the capacity can reach 326 mA h g(-1) even at
      4000 mA g(-1) and remains stable at ~610 mA h g(-1) without fading up to 300
      cycles when the rate is brought back to 200 mA g(-1). The excellent
      electrochemical performance is attributed to the synergetic effects between the
      ultrasmall SnS2 and the highly conductive graphene network. The unique structure
      can simultaneously facilitate Na(+) ion diffusion, provide more reaction sites,
      and suppress aggregation and volume fluctuation of the active materials during
      prolonged cycling.

PMID- 25367598
TI  - Impact of maternal and paternal preconception health on birth outcomes using
      prospective couples' data in Add Health.
AB  - PURPOSE: Retrospective studies of preconception health have demonstrated that
      parents' health conditions and behaviors can impact a newborn's birth outcomes
      and, subsequently, future health status. This study sought to examine the impact
      of preconception health, measured prospectively, among both mothers and fathers,
      on two important birth outcomes: birthweight and gestational age. METHODS: Data
      came from Add Health (the National Longitudinal Study of Adolescent Health),
      which included interviews with original participants and a subsample of their
      partners in 2001-02. In 2008, the original respondents again completed an
      interview for Add Health. For 372 eligible infants born to these couples, birth
      outcomes (measured in 2008) were regressed on preconception health conditions and
      behaviors among non-pregnant heterosexual partners (measured in 2001-02).
      RESULTS: Mean birthweight was 3,399 g, and mean gestational age was 39 weeks.
      Birthweight was higher for infants born to mothers with diabetes or high blood
      pressure, and for mothers who drank alcohol at least once per month, and lower
      for infants born to fathers with diabetes (p < 0.05). Infant gestational age was
      marginally lower for infants born to mothers with higher levels of depression (p
      < 0.10), and lower for infants born to fathers with diabetes and with higher
      levels of fast food consumption (p < 0.05). CONCLUSIONS: Both maternal and
      paternal preconception health conditions and behaviors influenced infant birth
      outcomes. Interventions to promote preconception health should focus on
      prevention of diabetes and high blood pressure, as well as minimizing consumption
      of alcohol and fast food.

PMID- 25367599
TI  - Transplantation of endothelial progenitor cells for improving placental perfusion
      in preeclamptic rats.
AB  - OBJECTIVE: Effective treatments for preeclampsia are currently unavailable. As
      endothelial progenitor cell-transplantation may improve ischemia, it is an
      important undertaking to study the role of endothelial progenitor cells for
      improving the symptom of preeclampsia. METHOD: Physiological and pathological
      changes in foetal rats and pregnant rats were monitored. Endothelial progenitor
      cells were isolated from the peripheral blood of normal rats and labelled by DiI.
      Endothelial progenitor cells were transplanted into the placenta of preeclampsia
      like rats. Fluorescence microscopy was used to observe the differentiation of
      transplanted endothelial progenitor cells. Western blotting was used to observe
      the expression of nestin, an index of brain hypoxia in foetal rats. RESULT: The
      rats suffered from abdominal aortic constriction and NG-nitro-L-arginine methyl
      ester injection (group F). The proteinuria and blood pressure of pregnant rats in
      group F increased on the 13th day of pregnancy. The proteinuria and blood
      pressure of group F was higher than in other groups of rats. The weight of foetal
      rats and foetal heads significantly decreased in group F compared with other
      groups. Typical pathological changes of preeclampsia were observed in the
      placental tissue of group F. In preeclampsia-like rats, transplantation of
      endothelial progenitor cells led to an increase in placenta angiogenesis. The
      expression of nestin weakened in endothelial progenitor cell-transplanted rats
      compared with the non-transplantation group. After EPCs transplantation,
      physiological parameters in the preeclampsia-like rats were significantly
      decreased. CONCLUSION: Endothelial progenitor cells transplantation could improve
      preeclampsia-like symptom in rats and endothelial progenitor cell-transplantation
      relieves intrauterine hypoxia in brain tissues of foetal rats to a certain
      extent.

PMID- 25367600
TI  - Accuracy of endometrial sampling compared to conventional dilatation and
      curettage in women with abnormal uterine bleeding.
AB  - OBJECTIVES: To compare the diagnostic accuracy of brush endometrial sampling with
      conventional dilatation and curettage in women with abnormal uterine bleeding.
      PATIENTS AND METHODS: Two hundred and twenty (220) women with abnormal uterine
      bleeding were included in this comparative study; endometrial sampling was done
      before cervical dilatation using Tao Bruch followed by conventional dilatation
      and curettage (D&C). The histopathology report of the Tao Bruch samples was
      compared with that of the D&C samples and the D&C results were considered as the
      gold standard. RESULTS: 100% of samples obtained by conventional D&C, while 98.2%
      of the samples obtained by Tao Brush were adequate for histopathology
      examination. In this study; Tao Brush had 100% sensitivity, 100% specificity,
      100% predictive values and accuracy for diagnosing endometrial hyperplasia,
      endometrial carcinoma, proliferative and secretory endometrium, also, it had
      86.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99%
      negative predictive value (NPV) and accuracy for diagnosing endometritis (no
      significant difference compared to conventional D&C), while, it had 77.8%
      sensitivity, 100% specificity, 100% PPV and 99% NPV and accuracy for diagnosing
      endometrial polyps (no significant difference compared to conventional D&C)
      CONCLUSION: Endometrial sampling using endometrial brush cytology (EBC) is safe,
      accurate, cost-effective outpatient procedure, avoids general anesthesia with
      high sensitivity and specificity for detection of endometrial hyperplasia and
      endometrial carcinoma. EBC could be used as complementary diagnostic tool when
      hysteroscopic biopsies or other blinded procedures for endometrial sampling are
      unwanted or not available.

PMID- 25367601
TI  - Comparison of efficacy of bromocriptine and cabergoline to GnRH agonist in a rat
      endometriosis model.
AB  - OBJECTIVE: To determine the effect of dopamine agonists in a surgically induced
      endometriosis model on rats. STUDY DESIGN: In this prospective randomized
      experimental study, surgical induction of endometriosis was performed by
      autotransplantation technique on 52 adult female Wistar-Albino rats.
      Endometriosis formation was confirmed by a second-look laparotomy (n:48) 1 month
      later. Four study groups were randomly generated according to their treatment
      regimens: group 1 (leuprolide acetate, n = 12), group 2 (bromocriptine, n = 12),
      group 3 (cabergoline, n = 12) and group 4 (control, n = 12). Endometriotic
      implants were excised for histopathological examination after treatment at the
      setting of laparotomy. The mean surface areas and histopathological glandular
      tissue (GT) and stromal tissue (ST) scores of endometriotic implants were studied
      and compared among groups. RESULTS: After 30 days of treatment, the mean surface
      area of the endometriotic implants of leuprolide acetate, bromocriptine and
      cabergoline groups was significantly decreased. The regression of endometriotic
      foci size in comparison to control was highest in group 1, followed by group 2,
      then group 3. In the histopathological evaluation both the ST and GT scores of
      group 1, 2 and 3 were significantly decreased in comparison to controls without a
      statistically significant difference between the groups. CONCLUSION: Dopamine
      agonists are as effective as GnRH agonists in the regression of experimental
      endometriotic implants in rats. Further trials are needed to elucidate the
      pathways affected by dopamine agonists.

PMID- 25367602
TI  - Diagnostic and therapeutic advancements for aerobic vaginitis.
AB  - BACKGROUND: Aerobic vaginitis (AV) is a newly defined clinical entity that is
      distinct from candidiasis, trichomoniasis and bacterial vaginosis (BV). Because
      of the poor recognition of AV, this condition can lead to treatment failures and
      is associated with severe complications, such as pelvic inflammatory disease,
      infertility, preterm birth and foetal infections. OBJECTIVE: This review
      describes the diagnosis and treatment of AV and the relationship between AV and
      pregnancy. RESULTS: The characteristics of AV include severely depressed levels
      of lactobacilli, increased levels of aerobic bacteria and an inflamed vagina. The
      diagnosis is made by microscopy on wet mounts of fresh vaginal fluid, and some
      distinct clinical features are recognized. Vaginal suppositories that contain
      kanamycin or clindamycin have shown curative effects in nonpregnant women.
      Additionally, the application of topical probiotics can restore the vaginal flora
      and reduce the recurrence of AV. Clindamycin vaginal suppositories and probiotics
      may be a better choice for gravida with AV than metronidazole. AV requires prompt
      attention, and the early diagnosis and treatment of AV during pregnancy
      significantly improves perinatal outcomes. CONCLUSION: Further research is needed
      to define the pathogenesis, diagnostic criteria and standard treatment guidelines
      for AV.

PMID- 25367603
TI  - Primary hyperparathyroidism during pregnancy.
AB  - PURPOSE: Primary hyperparathyroidism (pHPT) during pregnancy is rare and
      associated with increased morbidity and mortality for both mother and fetus. This
      review aims to draw together recent thinking on pregnancy and pHPT. METHODS: We
      have performed a Pubmed (Medline((r))) search with no time limit using "primary
      hyperparathyroidism", "pregnancy" or "management" as keywords. We reviewed 37
      articles in English and French languages on pHPT characteristics, clinical
      presentations, pregnancy complications, birth outcomes and management of pHPT
      during pregnancy. RESULTS: The diagnosis of pHPT is characterized by an elevated
      serum calcium level associated with an inappropriate increase in the parathyroid
      hormone level. The clinical manifestations are directly related to the calcium
      level. Usual techniques to detect parathyroid adenoma or hyperplasia, as
      computerized tomography and 99mTc-sestamibi scintigraphy, are not recommended in
      pregnancy. Thus, ultrasonography of the neck is the current first-line
      investigation during pregnancy for localization of parathyroid diseases. pHPT
      during pregnancy with mildly elevated calcium levels may be managed with medical
      treatment: intravenous or oral rehydratation, with or without forced diuresis.
      Few drugs are available for pHTP during pregnancy; calcitonin and cinacalcet
      require further study; bisphosphonate should be restricted to life-threatening
      hypercalcemia. Surgery is the only curative treatment and is recommended when
      calcium levels are above 2.75 mmol/L. It should be performed in the second
      trimester and considered in the third trimester if there is inadequate response
      to medical therapy. CONCLUSION: Early diagnosis of pHPT in a pregnant woman,
      followed by appropriate management and treatment, has been shown to significantly
      reduce maternal and fetal complications.

PMID- 25367604
TI  - Additional prognostic value of lymph node ratio over pN staging in different
      breast cancer subtypes based on the results of 1,656 patients.
AB  - PURPOSE: Although the impact of lymph node ratio (LNR: ratio of metastatic to
      resected LNs) in breast cancer (BC) has been investigated, its prognostic value
      in molecular subtypes remains unclear. Our aim was to evaluate the impact of LNR
      compared to pN-stage in BC subtypes. PATIENTS/METHODS: We analyzed the impact of
      LNR and pN-stage on disease-free (DFS) and overall survival (OS) in 1,656
      patients with primary BC who underwent primary axillary surgery (removal of >=10
      LNs) between 1998 and 2011. The cut-off points for LNR were previously published.
      Using immunohistochemical parameters tumors were grouped in luminalA,
      luminalB/HER2-, luminalB/HER2+, HER2+ and triple negative (TNBC). RESULTS: For
      the entire cohort 5/10-year DFS and OS rates were 88/77% and 88/75%,
      respectively. LNR and pN-stage were independent prognostic parameters for DFS/OS
      in multivariate analysis in the entire cohort and each molecular subgroup (p <
      0.001). However, increasing LNR seemed to discriminated 10-year DFS slightly
      better than pN-stage in luminalA (intermediate/high LNR 65/44% versus pN2/pN3
      71/53%), luminalB/HER2- (intermediate/high LNR 48/24% versus pN2/pN3 41/42%), and
      TNBC patients (intermediate/high LNR 49/24% versus pN2/pN3 56/33%). CONCLUSIONS:
      LNR is an important prognostic parameter for DFS/OS and might provide potentially
      more information than pN-stage in different molecular subtypes.

PMID- 25367605
TI  - New Phytologist next generation scientists.

PMID- 25367606
TI  - Calcium signals in plant immunity: a spiky issue.

PMID- 25367607
TI  - New Phytologist next generation scientists.

PMID- 25367608
TI  - Crassulacean acid metabolism biology.

PMID- 25367609
TI  - Progress in understanding the mechanisms and functional importance of protein
      membrane interactions in plants.

PMID- 25367610
TI  - Using results from global change experiments to inform land model development and
      calibration.

PMID- 25367611
TI  - Knowing your friends and foes--plant receptor-like kinases as initiators of
      symbiosis or defence.
AB  - The decision between defence and symbiosis signalling in plants involves
      alternative and modular plasma membrane-localized receptor complexes. A critical
      step in their activation is ligand-induced homo- or hetero-oligomerization of
      leucine-rich repeat (LRR)- and/or lysin motif (LysM) receptor-like kinases
      (RLKs). In defence signalling, receptor complexes form upon binding of pathogen
      associated molecular patterns (PAMPs), including the bacterial flagellin-derived
      peptide flg22, or chitin. Similar mechanisms are likely to operate during the
      perception of microbial symbiont-derived (lipo)-chitooligosaccharides. The
      structurally related chitin-oligomer ligands chitooctaose and chitotetraose
      trigger defence and symbiosis signalling, respectively, and their discrimination
      involves closely related, if not identical, LysM-RLKs. This illustrates the
      demand for and the challenges imposed on decision mechanisms that ensure
      appropriate signal initiation. Appropriate signalling critically depends on
      abundance and localization of RLKs at the cell surface. This is regulated by
      internalization, which also provides a mechanism for the removal of activated
      signalling RLKs. Abundance of the malectin-like domain (MLD)-LRR-RLK Symbiosis
      Receptor-like Kinase (SYMRK) is additionally controlled by cleavage of its
      modular ectodomain, which generates a truncated and rapidly degraded RLK
      fragment. This review explores LRR- and LysM-mediated signalling, the involvement
      of MLD-LRR-RLKs in symbiosis and defence, and the role of endocytosis in RLK
      function. 

PMID- 25367612
TI  - The effect of conventional mechanical periodontal treatment on red complex
      microorganisms and clinical parameters in Down syndrome periodontitis patients: a
      pilot study.
AB  - Periodontal disease (PD) is induced by a complex microbiota, such as
      Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola (together
      called the red complex), which triggers intense inflammatory reaction. Down
      syndrome (DS) individuals demonstrate a high prevalence of PD compared with those
      who are otherwise chromosomally normal (euploids). This pilot study aimed to
      evaluate the effect of non-surgical periodontal treatment in DS chronic
      periodontitis patients on clinical and microbiological parameters. Patients with
      chronic periodontitis, 23 DS and 12 euploids (control group), were submitted to
      non-surgical mechanical periodontal treatment, followed by maintenance for 45
      days. Clinical parameters after periodontal treatment were similar in diseased
      and healthy sites, independent of the genetic background. Diseased sites of DS
      and control patients harbored similar levels of P. gingivalis and T. forsythia at
      baseline, but significantly higher levels of T. denticola were found in DS
      patients. Increased levels of P. gingivalis at healthy sites were found in DS
      individuals. Non-surgical periodontal therapy decreased the levels of red complex
      microorganisms and improved the tested clinical parameters of diseased sites in
      both groups. However, the levels of red complex bacteria were higher in diseased
      sites of DS patients after the periodontal treatment. We conclude in this pilot
      study that, although the mechanical periodontal treatment seemed to be effective
      in DS subjects over a short-term period, the red complex bacteria levels did not
      decrease significantly in diseased sites, as occurred in controls. Therefore, for
      DS patients, it seems that the conventional non-surgical periodontal therapy
      should be improved by utilizing adjuvants to reduce the presence of
      periodontopathogens. 

PMID- 25367613
TI  - Open-source, high-throughput ultrasound treatment chamber.
AB  - Studying the effects of ultrasound on biological cells requires extensive
      knowledge of both the physical ultrasound and cellular biology. Translating
      knowledge between these fields can be complicated and time consuming. With the
      vast range of ultrasonic equipment available, nearly every research group uses
      different or unique devices. Hence, recreating the experimental conditions and
      results may be expensive or difficult. For this reason, we have developed devices
      to combat the common problems seen in state-of-the-art biomedical ultrasound
      research. In this paper, we present the design, fabrication, and characterisation
      of an open-source device that is easy to manufacture, allows for parallel sample
      sonication, and is highly reproducible, with complete acoustic calibration. This
      device is designed to act as a template for sample sonication experiments. We
      demonstrate the fabrication technique for devices designed to sonicate 24-well
      plates and OptiCellTM using three-dimensional (3D) printing and low-cost
      consumables. We increased the pressure output by electrical impedance matching of
      the transducers using transmission line transformers, resulting in an increase by
      a factor of 3.15. The devices cost approximately ?220 in consumables, with a
      major portion attributed to the 3D printing, and can be fabricated in
      approximately 8 working hours. Our results show that, if our protocol is
      followed, the mean acoustic output between devices has a variance of <1%. We
      openly provide the 3D files and operation software allowing any laboratory to
      fabricate and use these devices at minimal cost and without substantial prior
      know-how.

PMID- 25367614
TI  - CYP 2C19 and UDP-glucuronosyltransferases not only for drugs but also for
      endobiotics.

PMID- 25367615
TI  - Harmonisation of specialist training and continuing professional development in
      laboratory medicine: a long but necessary journey.

PMID- 25367616
TI  - CCLM award for the most cited paper recently published.

PMID- 25367617
TI  - Telocytes revisited.
AB  - Telocytes (TCs) are a novel interstitial (stromal) cell type described in many
      tissues and organs (www.telocytes.com). A TC is characterized by a small cell
      body (9-15 MUm) and a variable number (one to five) of extremely long and thin
      telopodes (Tps), with alternating regions of podomers (~80 nm) and podoms (250
      300 nm). Tps are interconnected by homo- and heterocellular junctions and form
      three-dimensional networks. Moreover, Tps release three types of extracellular
      vesicles: exosomes, ectosomes, and multivesicular cargos, which are involved in
      paracrine signaling. Different techniques have been used to characterize TCs,
      from classical methods (light microscopy, electron microscopy) to modern 'omics'.
      It is considered that electron microscopy is essential for their identification,
      and CD34/PDGFRalpha double immunohistochemistry can orientate the diagnosis.
      Functional evidence is accumulating that TCs may be intimately involved in the
      maintenance of tissue homeostasis and renewal by short- and long-distance
      intercellular communication. This review focuses on the most recent findings
      regarding TC features and locations and the principal hypotheses about their
      functions in normal and diseased organs. TC involvement in regenerative medicine
      is also considered.

PMID- 25367618
TI  - Mesencephalic GABA neuronal development: no more on the other side of oblivion.
AB  - Midbrain GABA neurons, endowed with multiple morphological, physiological and
      molecular characteristics as well as projection patterns are key players
      interacting with diverse regions of the brain and capable of modulating several
      aspects of behavior. The diversity of these GABA neuronal populations based on
      their location and function in the dorsal, medial or ventral midbrain has
      challenged efforts to rapidly uncover their developmental regulation. Here we
      review recent developments that are beginning to illuminate transcriptional
      control of GABA neurons in the embryonic midbrain (mesencephalon) and discuss its
      implications for understanding and treatment of neurological and psychiatric
      illnesses.

PMID- 25367619
TI  - All motors have to decide is what to do with the DNA that is given them.
AB  - DNA translocases are a diverse group of molecular motors responsible for a wide
      variety of cellular functions. The goal of this review is to identify common
      aspects in the mechanisms for how these enzymes couple the binding and hydrolysis
      of ATP to their movement along DNA. Not surprisingly, the shared structural
      components contained within the catalytic domains of several of these motors
      appear to give rise to common aspects of DNA translocation. Perhaps more
      interesting, however, are the differences between the families of translocases
      and the potential associated implications both for the functions of the members
      of these families and for the evolution of these families. However, as there are
      few translocases for which complete characterizations of the mechanisms of DNA
      binding, DNA translocation, and DNA-stimulated ATPase have been completed, it is
      difficult to form many inferences. We therefore hope that this review motivates
      the necessary further experimentation required for broader comparisons and
      conclusions.

PMID- 25367620
TI  - DNA-bound metal ions: recent developments.
AB  - The affinity of metal ions for DNA is logical considering that the structure of
      DNA includes a phosphate backbone with a net-negative charge, a deoxyribose sugar
      with O atoms, and purine and pyrimidine bases that contain O and N atoms. DNA
      metal ion interactions encompass a large area of research that ranges from the
      most fundamental characterization of DNA-metal ion binding to the role of DNA
      bound metal ions in disease and human health. Alternative DNA base pairing
      mediated by metal binding is also being investigated and manipulated for
      applications in logic gates, molecular machines, and nanotechnology. This review
      highlights recent work aimed at understanding interactions of redox-active metal
      ions with DNA that provides a better understanding of the mechanisms by which
      various types of oxidative DNA damage (strand breakage and base modifications)
      occur. Antioxidants that mitigate oxidative DNA damage by coordinating metal ions
      that produce reactive oxygen species are addressed, as well as recent work on the
      effect of DNA-metal ion interactions and the efficacy of quinolone-based
      antibacterial drugs. Recent advances in metal-mediated base pairing that triggers
      conformational changes in DNA structure for use as selective metal ion sensors
      and novel nanotechnology applications are also included.

PMID- 25367621
TI  - Regulation of LINE-1 in mammals.
AB  - Transposable elements (TEs) are mobile DNA elements that represent almost half of
      the human genome. Transposition of TEs has been implicated as a source of genome
      evolution and acquisition of new traits but also as an origin of diseases. The
      activity of these elements is therefore tightly regulated during the life cycle
      of each individual, and many recent discoveries involved the genetic and
      epigenetic mechanisms in their control. In this review, we present recent
      findings in this field of research, focusing on the case of one specific family
      of TEs: the long-interspersed nuclear elements-1 (LINE-1 or L1). LINE-1 elements
      are the most representative class of retrotransposons in mammalian genomes. We
      illustrate how these elements are conserved between mice and humans, and how they
      are regulated during the life cycle. Additionally, recent advances in genome-wide
      sequencing approaches allow us not only to better understand the regulation of
      LINE-1 but also highlight new issues specifically at the bioinformatics level.
      Therefore, we discuss the state of the art in analyzing such bioinformatics
      datasets to identify epigenetic regulators of repeated elements in the human
      genomes.

PMID- 25367622
TI  - Glycolipozyme membrane protein integrase (MPIase): recent data.
AB  - A novel factor for membrane protein integration, from the cytoplasmic membrane of
      Escherichia coli, named MPIase (membrane protein integrase), has recently been
      identified and characterized. MPIase was revealed to be essential for the
      membrane integration of a subset of membrane proteins, despite that such
      integration reactions have been, thus far, thought to occur spontaneously. The
      structure determination study revealed that MPIase is a novel glycolipid
      comprising a glycan chain with three N-acetylated amino sugars connected to
      diacylglycerol through a pyrophosphate linker. As MPIase catalyzes membrane
      protein integration, we propose that MPIase is a glycolipozyme on the basis of
      its enzyme-like function. The glycan chain exhibits a molecular chaperone-like
      function by directly interacting with substrate membrane proteins. Moreover,
      MPIase also affects the dimer structure of SecYEG, a translocon, thereby
      significantly stimulating preprotein translocation. The molecular mechanisms of
      MPIase functions will be outlined.

PMID- 25367623
TI  - Killer immunoglobulin-like receptor diversity in Malay subethnic groups of
      Peninsular Malaysia.
AB  - The KIR system shows variation at both gene content and allelic level across
      individual genome and populations. This variation reflects its role in immunity
      and has become a significant tool for population comparisons. In this study, we
      investigate KIR gene content in 120 unrelated individuals from the four Malay
      subethnic groups (Kelantan, Jawa, Banjar and Pattani Malays). Genotyping using
      commercial polymerase chain reaction-sequence-specific primer (PCR-SSP) kits
      revealed a total of 34 different KIR genotypes; 17 for Kelantan, 15 for Banjar,
      14 for Jawa and 13 for Pattani Malays. Two new variants observed in Banjar Malays
      have not previously been reported. Genotype AA and haplotype A were the most
      common in Jawa (0.47 and 0.65, respectively), Banjar (0.37 and 0.52,
      respectively) and Pattani (0.40 and 0.60, respectively) Malays. In contrast,
      Kelantan Malays were observed to have slightly higher frequency (0.43) of
      genotype BB as compared with the others. Based on the KIR genes distribution,
      Jawa, Pattani and Banjar subethnic groups showed greater similarity and are
      discrete from Kelantan Malays. A principal component plot carried out using KIR
      gene carrier frequency shows that the four Malay subethnic groups are clustered
      together with other South-East Asian populations. Overall, our observation on
      prevalence of KIR gene content demonstrates genetic affinities between the four
      Malay subethnic groups and supports the common origins of the Austronesian
      speaking people.

PMID- 25367624
TI  - Healing Words: Using Affect Labeling to Reduce the Effects of Unpleasant Cues on
      Symptom Reporting in IBS Patients.
AB  - PURPOSE: The present study aimed to induce elevated symptom reports through the
      presentation of unpleasant cues in patients with irritable bowel syndrome (IBS)
      and examine whether applying an emotion regulation technique (affect labeling)
      can reduce symptom reporting in patients. METHODS: Patients diagnosed with IBS (N
      = 29) and healthy controls (N = 26) were presented with six picture series (three
      pleasant, three unpleasant) under three within-subject conditions: merely
      viewing, emotional labeling, or content (non-emotional) labeling. Each picture
      viewing trial was followed by affect ratings and a symptom checklist, consisting
      of general arousal and IBS-specific symptoms. RESULTS: Viewing unpleasant
      pictures led to overall increased symptom reports, both for arousal and
      gastrointestinal symptoms, in both groups. Labeling the pictures did not reduce
      these effects significantly, although a trend toward less arousal symptoms after
      unpleasant cues emerged in the patient group only, especially during emotional
      labeling. CONCLUSIONS: Current findings indicate that the mere presentation of
      unpleasant cues can induce elevated symptom reports in IBS patients. The results
      of the labeling manipulation provide modest support for the effectiveness of
      emotion regulation strategies in reversing these effects of unpleasant cues in
      patients suffering from functional syndromes. Methodological issues that may have
      confounded present results are discussed.

PMID- 25367625
TI  - Spatial structuring of bacterial communities within individual Ginkgo biloba
      trees.
AB  - Plant-associated microorganisms affect the health of their hosts in diverse ways,
      yet the distribution of these organisms within individual plants remains poorly
      understood. To address this knowledge gap, we assessed the spatial variability in
      bacterial community diversity and composition found on and in aboveground tissues
      of individual Ginkgo biloba trees. We sampled bacterial communities from > 100
      locations per tree, including leaf, branch and trunk samples and used high
      throughput sequencing of the 16S rRNA gene to determine the diversity and
      composition of these communities. Bacterial community structure differed strongly
      between bark and leaf samples, with bark samples harbouring much greater
      bacterial diversity and a community composition distinct from leaves. Within
      sample types, we observed clear spatial patterns in bacterial diversity and
      community composition that corresponded to the samples' proximity to the exterior
      of the tree. The composition of the bacterial communities found on trees is
      highly variable, but this variability is predictable and dependent on sampling
      location. Moreover, this work highlights the importance of carefully considering
      plant spatial structure when characterizing the microbial communities associated
      with plants and their impacts on plant hosts. 

PMID- 25367626
TI  - Divergent total synthesis of the tricyclic marine alkaloids lepadiformine,
      fasicularin, and isomers of polycitorols by reagent-controlled diastereoselective
      reductive amination.
AB  - We describe a flexible and divergent route to the pyrrolo-/pyrido[1,2-j]quinoline
      frameworks of tricyclic marine alkaloids via a common intermediate formed by the
      ester-enolate Claisen rearrangement of a cyclic amino acid allylic ester. We have
      synthesized the proposed structure of polycitorols and demonstrated that the
      structure of these alkaloids requires revision. In addition to asymmetric formal
      syntheses, stereoselective and concise total syntheses of (-)-lepadiformine and (
      )-fasicularin were also accomplished from simple, commercially available starting
      materials in a completely substrate-controlled manner. The key step in these
      total syntheses was the reagent-dependent stereoselective reductive amination of
      the common intermediate to yield either indolizidines 55 a or 55 b. Aziridinium
      mediated carbon homologation of the hindered C-10 group to the homoallylic group
      facilitated the synthesis. 

PMID- 25367627
TI  - Fracture strain of SiC nanowires and direct evidence of electron-beam induced
      amorphisation in the strained nanowires.
AB  - SiC nanowires with diameters ranging from 29 to 270 nm exhibit an average strain
      of 5.5% with a maximum of up to 7.0%. The brittle fracture of the nano-wires
      being measured was confirmed by transmission electron microscopy (TEM) analysis.
      This study demonstrates that amorphisation occurs in the stained SiC nanowires
      during normal TEM examination, which could be induced by electron irradiation. 

PMID- 25367628
TI  - Chemerin is a novel biomarker of acute coronary syndrome but not of stable angina
      pectoris.
AB  - BACKGROUND: Recent evidence demonstrated that the circulating adipokines were
      associated with the onset of acute coronary syndrome (ACS) including unstable
      angina pectoris (UAP) and acute myocardial infarction (AMI). As a novel
      adipokine, chemerin has been related to atherosclerosis and the presence of
      coronary artery disease. However, the plasma levels of chemerin in patients with
      ACS have yet to be investigated. METHODS: Plasma levels of chemerin and
      adiponectin were measured by an enzyme-linked immunosorbent assay (ELISA) in 60
      patients with stable angina pectoris (SAP), 60 patients with UAP, 60 patients
      with AMI and 40 control patients. Left ventricular end-diastolic diameter (LVEDD)
      and left ventricular ejection fraction (LVEF) were measured using a GE ViVid E7
      ultrasonography machine, and the severity of coronary stenosis in patients was
      estimated with a Gensini coronary score following coronary angiography. RESULTS:
      Plasma chemerin levels were significantly higher in ACS patients than in the
      control and SAP groups, while plasma adiponectin levels were significantly lower
      in ACS patients than the control group. A correlation analysis revealed that
      plasma chemerin levels were positively correlated with the levels of C-reactive
      protein (CRP) (r = 0.29, P < 0.01) and LVEDD (r = 0.27, P < 0.01) but negatively
      correlated with LVEF (r = -0.45, P < 0.01) and that plasma adiponectin levels
      were positively correlated with LVEF (r = 0.53, P < 0.01) but negatively
      correlated with CRP (r = -0.33, P < 0.01) and LVEDD (r = -0.30, P < 0.01).
      Although significant correlations between chemerin, adiponectin and BMI or the
      Gensini coronary score were found in patients with SAP, neither chemerin nor
      adiponectin was correlated with BMI and the Gensini coronary score in patients
      with ACS. Furthermore, both chemerin (OR 1.103, 95% CI 1.065 to 1.142; P = 0.001)
      and adiponectin (OR 0.871, 95% CI 0.776 to 0.970; P = 0.018) were independently
      associated with the presence of ACS. CONCLUSIONS: Chemerin is a novel biomarker
      of acute coronary syndrome but not of stable angina pectoris.

PMID- 25367631
TI  - Editorial: Current status and prospects on nucleic acid transfer.

PMID- 25367629
TI  - The role of small RNAs on phenotypes in reciprocal hybrids between Solanum
      lycopersicum and S. pimpinellifolium.
AB  - BACKGROUND: Reciprocal hybrids showing different phenotypes have been well
      documented in previous studies, and many factors accounting for different
      phenotypes have been extensively investigated. However, less is known about
      whether the profiles of small RNAs differ between reciprocal hybrids and how
      these small RNAs affect gene expression and phenotypes. To better understand this
      mechanism, the role of small RNAs on phenotypes in reciprocal hybrids was
      analysed. RESULTS: Reciprocal hybrids between Solanum lycopersicum cv. Micro-Tom
      and S. pimpinellifolium line WVa700 were generated. Significantly different
      phenotypes between the reciprocal hybrids were observed, including fruit shape
      index, single fruit weight and plant height. Then, through the high-throughput
      sequencing of small RNAs, we found that the expression levels of 76 known miRNAs
      were highly variable between the reciprocal hybrids. Subsequently, a total of 410
      target genes were predicted to correspond with these differentially expressed
      miRNAs. Furthermore, gene ontology (GO) annotation indicated that those target
      genes are primarily involved in metabolic processes. Finally, differentially
      expressed miRNAs, such as miR156f and 171a, and their target genes were analysed
      by qRT-PCR, and their expression levels were well correlated with the different
      phenotypes. CONCLUSIONS: This study showed that the profiles of small RNAs
      differed between the reciprocal hybrids, and differentially expressed genes were
      also observed based on the different phenotypes. The qRT-PCR results of target
      genes showed that differentially expressed miRNAs negatively regulated their
      target genes. Moreover, the expression of target genes was well correlated with
      the observations of different phenotypes. These findings may aid in elucidating
      small RNAs contribute significantly to different phenotypes through epigenetic
      modification during reciprocal crossing.

PMID- 25367630
TI  - ABCB4 is frequently epigenetically silenced in human cancers and inhibits tumor
      growth.
AB  - Epigenetic silencing through promoter hypermethylation is an important hallmark
      for the inactivation of tumor-related genes in carcinogenesis. Here we identified
      the ATP-binding cassette sub-family B member 4 (ABCB4) as a novel epigenetically
      silenced target gene. We investigated the epigenetic regulation of ABCB4 in 26
      human lung, breast, skin, liver, head and neck cancer cells lines and in primary
      cancers by methylation and expression analysis. Hypermethylation of the ABCB4 CpG
      island promoter occurred in 16 out of 26 (62%) human cancer cell lines. Aberrant
      methylation of ABCB4 was also revealed in 39% of primary lung cancer and in 20%
      of head and neck cancer tissues. In 37% of primary lung cancer samples, ABCB4
      expression was absent. For breast cancer a significant hypermethylation occurred
      in tumor tissues (41%) compared to matching normal samples (0%, p = 0.002).
      Silencing of ABCB4 was reversed by 5-aza-2'-deoxycytidine and zebularine
      treatments leading to its reexpression in cancer cells. Overexpression of ABCB4
      significantly suppressed colony formation and proliferation of lung cancer cells.
      Hypermethylation of Abcb4 occurred also in murine cancer, but was not found in
      normal tissues. Our findings suggest that ABCB4 is a frequently silenced gene in
      different cancers and it may act tumor suppressivly in lung cancer. 

PMID- 25367636
TI  - Changes in self-reported sleep and cognitive failures: a randomized controlled
      trial of a stress management intervention.
AB  - OBJECTIVES: This study evaluated the effectiveness of a stress management
      intervention combining individual cognitive behavioral therapy (CBT) with a brief
      workplace intervention on self-reported measures of sleep and cognitive
      functioning among patients on sick leave due to work-related stress complaints.
      METHODS: Participants were patients referred to the regional Department of
      Occupational Medicine. Inclusion criteria were (i) sick leave due to work-related
      stress complaints and (ii) a diagnosis of adjustment disorder/reactions to stress
      or mild depression. Participants (N=137) were randomized to either an
      intervention (N=57) or control (N=80) group. The intervention comprised six
      sessions with a psychologist and the offer of a small workplace intervention.
      Questionnaires were answered at baseline and after 4, and 10 months. RESULTS:
      Symptoms were significantly reduced over time in both groups but there was no
      significant treatment effect on sleep or cognitive outcomes at any time point.
      From 0-4 months, there was a tendency for larger improvements in the intervention
      group with regards to sleep and cognitive failures in distraction. Although
      neither was significant, the results came close to significance depicting a small
      effect size (Cohen's d) on sleep complaints and distractions (but not memory).
      CONCLUSIONS: The specific intervention was not superior to the control condition
      in reducing symptoms of sleep problems and cognitive difficulties at any time
      point during the 10-month follow-up period. Substantial improvements in symptoms
      over time were seen in both groups.

PMID- 25367637
TI  - More than seizures: improving the lives of people with refractory epilepsy.
AB  - As captured by the proposed new definition, epilepsy is increasingly recognized
      as a disorder characterized not only by an enduring predisposition to recurrent
      seizures but explicitly also by the neurobiological, cognitive, psychological and
      social consequences of this condition. Further, both in the estimated 15 million
      people worldwide who have ongoing seizures despite optimal management and in a
      substantial proportion of those in remission, the consequences and comorbidities
      of epilepsy are the major determinants of quality of life. These include mood
      disorders such as anxiety and depression, dose related and longer term effects of
      antiepileptic drugs, including on prenatal development and bone health, and
      neurobehavioural effects. Whilst separating those that are part of an underlying
      condition or have unrelated contributors from those that are potentially
      remediable can be difficult, given the range of tools now available to assist
      with screening and management there is no excuse for not at least trying as part
      of standard care for people with epilepsy. Managing epilepsy well is about much
      more than controlling seizures and this needs to be recognized in planning and
      delivering services, as well as in prioritizing research.

PMID- 25367638
TI  - A systematic mapping of funders of maternal health intervention research 2000
      2012.
AB  - BACKGROUND: The priorities of research funding bodies govern the research agenda,
      which has important implications for the provision of evidence to inform policy.
      This study examines the research funding landscape for maternal health
      interventions in low- and middle-income countries (LMICs). METHODS: This review
      draws on a database of 2340 academic papers collected through a large-scale
      systematic mapping of research on maternal health interventions in LMICs
      published from 2000-2012. The names of funders acknowledged on each paper were
      extracted and categorised into groups. It was noted whether support took a
      specific form, such as staff fellowships or drugs. Variations between funder
      types across regions and topics of research were assessed. RESULTS: Funding
      sources were only reported in 1572 (67%) of articles reviewed. A high number of
      different funders (685) were acknowledged, but only a few dominated funding of
      published research. Bilateral funders, national research agencies and private
      foundations were most prominent, while private companies were most commonly
      acknowledged for support 'in kind'. The intervention topics and geographic
      regions of research funded by the various funder types had much in common, with
      HIV being the most common topic and sub-Saharan Africa being the most common
      region for all types of funder. Publication outputs rose substantially for
      several funder types over the period, with the largest increase among bilateral
      funders. CONCLUSIONS: A considerable number of organisations provide funding for
      maternal health research, but a handful account for most funding
      acknowledgements. Broadly speaking, these organisations address similar topics
      and regions. This suggests little coordination between funding agencies, risking
      duplication and neglect of some areas of maternal health research, and limiting
      the ability of organisations to develop the specialised skills required for
      systematically addressing a research topic. Greater transparency in reporting of
      funding is required, as the role of funders in the research process is often
      unclear.

PMID- 25367639
TI  - Quinone diazides for olefin functionalization.
AB  - The utility of quinone diazides in materials science is vast and well-documented,
      yet this potentially useful motif has languished in the annals of organic
      synthesis. Herein we show that modern tools of catalysis can be employed with
      free or suitably masked quinone diazides to unleash the power of these classic
      diazo compounds in the context of both inter- and intramolecular olefin
      cyclopropanation. 

PMID- 25367640
TI  - Comparison of non-ablative and ablative fractional laser treatments in a
      postoperative scar study.
AB  - BACKGROUND AND OBJECTIVE: Postoperative scarring after thyroidectomy is a problem
      for both patients and clinicians. Recently, both non-ablative and ablative
      fractional laser (NFL and AFL) systems have attracted attention as potential
      therapies for the revision of thyroidectomy scars. The present split-scar study
      was designed to directly compare the efficacy of these two methods for the
      treatment of post-thyroidectomy scars. STUDY DESIGN/MATERIALS AND METHODS: Twenty
      females (mean age 42.1 years, range 22-55) with scarring 2-3 months post
      thyroidectomy were enrolled in the study. One half of the scar (chosen at random)
      was treated with NFL and the other half was treated with AFL. In each case, two
      treatments were given at 2-month intervals. Clinical photographs were taken at
      baseline, before each treatment, and at the final 3-month evaluation. Independent
      clinician grading of improvement and patient satisfaction were measured on a
      quartile scale. Color (erythema and melanin indices) and scar hardness were
      measured at baseline and at three months post-treatment with a dermaspectrometer
      and durometer, respectively. RESULTS: The mean clinical improvement grades for
      AFL and NFL were highly similar, 2.45 +/- 0.99 and 2.35 +/- 0.85, respectively,
      without statistical significance (P = 0.752). However, NFL treatment resulted in
      statistically significant changes in erythema and pigmentation (P = 0.035 and P =
      0.003, respectively), and skin hardness was significantly reduced after AFL
      treatment (P = 0.026). CONCLUSIONS: Clinical improvement was not significantly
      different between the two systems; however, AFL was better at reducing scar
      hardness whereas NFL was superior for lightening color. These data suggest that a
      study assessing the feasibility of a combined approach for the revision of post
      thyroidectomy scarring might be warranted.

PMID- 25367641
TI  - The toxicity of sediments from Taihu Lake evaluated by several in vitro
      bioassays.
AB  - In vitro bioassays are useful techniques for the determination of biological
      effects in sediment samples containing complex mixtures of contaminants. In this
      study, 28 surface sediment samples from Taihu Lake, East China, were collected
      for toxicity assessment using a battery of in vitro bioassays. The battery
      included a two-hybrid yeast bioassay for estrogenic and thyroidal effects, the
      H4IIE rat hepatoma cell bioassay for aryl hydrocarbon (Ah) receptor (Ah-agonists)
      mediated effects as measured by ethoxyresorufin-O-deethylase (EROD) activity, and
      the SOS/umu bioassay for genotoxic effects. Toxicities were expressed as 17beta
      estradiol equivalents (EEQs), T3 (3,5,3'-triiodothyronine) equivalents (T3-EQs),
      2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs), and induction ratios
      (IRs) of beta-galactosidase activity. The results showed that total estrogenic
      effects in sediment samples ranged from 0.0011 to 12.4 pg EEQ/g sediment [dry
      weight (d.w.)], the thyroidal effects ranged from 0.35 to 24.8 pg T3-EQ/g
      sediment (d.w.), the Ah-agonist effects varied from 2.70 to 37.8 pg TEQ/g
      sediment (d.w.), and the weight of soil required for the extracts to lead to a
      positive result (IR 2.0) in the SOS/umu bioassay was between 1.98 and 15.3 mg
      (d.w.) per well. Significantly positive correlations were only found between lgT3
      EQs and lgEEQs, which indicated similar spatial distributions of estrogenic and
      thyroidal effects in Taihu Lake. These results suggested that the applied battery
      of in vitro bioassays represented an efficient (fast and cost-effective)
      screening system for the identification of emerging contaminants in Taihu Lake
      and provided meaningful information for further analysis and risk evaluation.

PMID- 25367642
TI  - PFOS and PFOA in paired urine and blood from general adults and pregnant women:
      assessment of urinary elimination.
AB  - Although levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid
      (PFOA) in human blood are well documented, information on elimination of these
      chemicals is limited. In this study, PFOS and PFOA were analyzed in 81 whole
      blood-urine paired samples from general adults and pregnant women in Tianjin,
      China. PFOS and PFOA were detected in 48 and 76% of adult urine (AU) samples,
      with geometric mean (GM) concentrations of 0.011 and 0.008 ng/mL, respectively;
      whereas relatively low PFOS and PFOA concentrations were found in maternal urine
      (MU) samples, with GM concentrations of 0.006 and 0.003 ng/mL, respectively. For
      PFOA, the coefficients of Pearson's correlation between whole blood
      concentrations and creatinine-adjusted and creatinine-unadjusted urinary
      concentrations were 0.348 (p = 0.013) and 0.417 (p = 0.002), respectively. The GM
      urinary elimination rates of PFOS (PFOSUER) and PFOA (PFOAUER) were 16 and 25%,
      respectively, for adults. These results indicate that urine is an important
      pathway of excretion of perfluoroalkyl substances (PFASs). The partitioning
      ratios of PFAS concentration between urine and whole blood (PFASU/B) in pregnant
      women (PFOSU/B, 0.0004; PFOAU/B, 0.0011) were significantly lower (p = 0.025 for
      PFOSU/B, p = 0.017 for PFOAU/B) than the ratios found in non-pregnant women
      (PFOSU/B, 0.0013; PFOAU/B, 0.0028). Furthermore, our results suggest a clear
      gender difference in the urinary elimination of PFOA, with male adults (31%)
      having significantly higher PFOAUER than that of female adults (19%). PFOSUER was
      significantly inversely correlated with age (r = -0.334, p = 0.015); these
      findings suggest that urinary elimination of PFOS is faster in young adults than
      in the elderly.

PMID- 25367643
TI  - Identification of a putatively multixenobiotic resistance related Abcb1
      transporter in amphipod species endemic to the highly pristine Lake Baikal.
AB  - The fauna of Lake Baikal in Eastern Siberia, the largest freshwater body on
      Earth, is characterized by high degrees of biodiversity and endemism. Amphipods,
      a prominent taxon within the indigenous fauna, occur in an exceptionally high
      number of endemic species. Considering the specific water chemistry of Lake
      Baikal with extremely low levels of potentially toxic natural organic compounds,
      it seems conceivable that certain adaptions to adverse environmental factors are
      missing in endemic species, such as cellular defense mechanisms mitigating toxic
      effects of chemicals. The degree to which the endemic fauna is affected by the
      recently occurring anthropogenic water pollution of Lake Baikal may depend on the
      existence of such cellular defense mechanisms in those species. We here show that
      endemic amphipods express transcripts for Abcb1, a major component of the
      cellular multixenobiotic resistance (MXR) defense against toxic chemicals. Based
      on a partial abcb1 cDNA sequence from Gammarus lacustris, an amphipod species
      common across Northern Eurasia but only rarely found in Lake Baikal, respective
      homologous sequences were cloned from five amphipods endemic to Lake Baikal,
      Eulimnogammarus verrucosus, E. vittatus, E. cyaneus, E. marituji, and Gmelinoides
      fasciatus, confirming that abcb1 is transcribed in those species. The effects of
      thermal (25  degrees C) and chemical stress (1-2 mg L(-1) phenanthrene) in short
      term exposures (up to 24 h) on transcript levels of abcb1 and heat shock protein
      70 (hsp70), used as a proxy for cellular stress in the experiments, were
      exemplarily examined in E. verrucosus, E. cyaneus, and Gammarus lacustris.
      Whereas increases of abcb1 transcripts upon treatments occurred only in the
      Baikalian species E. verrucosus and E. cyaneus but not in Gammarus lacustris,
      changes of hsp70 transcript levels were seen in all three species. At least for
      species endemic to Lake Baikal, the data thus indicate that regulation of the
      identified amphipod abcb1 is triggered within the general cellular stress
      response. This is the first report presenting molecular data on a MXR transporter
      in amphipods, an ecotoxicologically important but with regard to gene sequence
      data comparatively little explored taxon. 

PMID- 25367644
TI  - Relevance of nonfunctional linear polyacrylic acid for the biodegradation of
      superabsorbent polymer in soils.
AB  - Biodegradability is a desired characteristic for synthetic soil amendments. Cross
      linked polyacrylic acid (PAA) is a synthetic superabsorbent used to increase the
      water availability for plant growth in soils. About 4% within products of cross
      linked PAA remains as linear polyacrylic acid (PAAlinear). PAAlinear has no
      superabsorbent function but may contribute to the apparent biodegradation of the
      overall product. This is the first study that shows specifically the
      biodegradation of PAAlinear in agricultural soil. Two (13)C-labeled PAAlinear of
      the average molecular weights of 530, 400, and 219,500 g mol(-1) were incubated
      in soil. Mineralization of PAAlinear was measured directly as the (13)CO2 efflux
      from incubation vessels using an automatic system, which is based on (13)C
      sensitive wavelength-scanned cavity ring-down spectroscopy. After 149 days, the
      PAAlinear with the larger average molecular weight and chain length showed about
      half of the degradation (0.91% of the initial weight) of the smaller PAAlinear
      (1.85%). The difference in biodegradation was confirmed by the delta(13)C
      signature of the microbial biomass (delta(13)Cmic), which was significantly
      enriched in the samples with short PAAlinear (-130/00 against reference Vienna
      Pee Dee Belemnite,VPDB) as compared to those with long PAAlinear (-160/00 VPDB).
      In agreement with other polymer studies, the results suggest that the
      biodegradation of PAAlinear in soil is determined by the average molecular weight
      and occurs mainly at terminal sites. Most importantly, the study outlines that
      the size of PAA that escapes cross-linking can have a significant impact on the
      overall biodegradability of a PAA-based superabsorbent.

PMID- 25367645
TI  - Urinary thiocyanate concentrations are associated with adult cancer and lung
      problems: US NHANES, 2009-2012.
AB  - Links between environmental chemicals and human health have emerged but the
      effects from perchlorate, nitrate and thiocyanate were unclear. Therefore, it was
      aimed to study the relationships of urinary perchlorate, nitrate and thiocyanate
      concentrations and adult health conditions in a national and population-based
      study. Data was retrieved from US National Health and Nutrition Examination
      Surveys, 2009-2012, including demographics, blood pressure readings, self
      reported health conditions and urinary perchlorate, nitrate and thiocyanate
      concentrations. Analyses included chi-square test, t test survey-weighted
      logistic regression models and population attributable risk estimation. There
      were no clear associations between urinary perchlorate concentrations and adult
      health conditions, although people with hearing loss and diabetes could be at the
      borderline risk. Urinary thiocyanate concentrations were significantly associated
      with emphysema (odds ratio (OR) 2.70 95% confidence intervals (CI) 1.91-3.82, P <
      0.001), cancer (OR 1.21 95%CI 1.06-1.39, P = 0.008), chronic bronchitis (OR 1.23
      95%CI 1.10-1.52, P = 0.003), wheezing (OR 1.24 95%CI 1.05-1.46, P = 0.011),
      coughing (OR 1.19 95%CI 1.03-1.37, P = 0.018) and sleep complaints (OR 1.14 95%CI
      1.02-1.26, P = 0.019). The population attributable risks accounted for 3.3% (1.8
      5.3%), 1.9% (0.6-3.5%), 1.2% (0.5-2.6%), 2.2% (0.5-4.1%), 1.8% (0.3-6.2%) and
      1.3% (0.2-2.4%) for emphysema, cancer, chronic bronchitis, wheezing, coughing and
      sleep complaints, respectively. In addition, there was an inverse association
      observed between urinary nitrate level and heart failure. This is for the first
      time observing significant risk effects of urinary thiocyanate concentrations on
      adult cancer and lung problems, although the causality cannot be established.
      Elimination of such environmental chemical in humans should be included in future
      health policy and intervention programs.

PMID- 25367646
TI  - Retrievable inferior vena cava filters can be placed and removed with a high
      degree of success: Initial experience.
AB  - OBJECTIVES: Evaluate the success rate of retrievable inferior vena cava filter
      (IVC) removal in a tertiary care practice. BACKGROUND: Retrievable IVC filters
      became readily available in the United States following Food and Drug
      Administration approval in 2003, and their use has increased dramatically. They
      represent an attractive option for patients with contraindications to
      anticoagulation who may only need short-term protection against pulmonary
      embolism. METHODS: All patients who had undergone placement of a retrievable IVC
      filter at Mayo Clinic between 2003 and 2005 were retrospectively reviewed to
      evaluate our initial experience with retrievable inferior vena cava filters at a
      large tertiary care center. RESULTS: During a three-year-period of time, Mayo
      Clinic, Rochester, MN placed 892 IVC filters of which 460 were retrievable. Of
      the 460 retrievable filters placed (249 Gunther Tulip(r), 207 Recovery(r), and 4
      OptEase(r)), retrieval was attempted in 223 (48.5%). Of 223 initial attempts, 196
      (87.9%) were initially successful and 27 (12.1%) were unsuccessful. Of the 27
      unsuccessful initial retrieval attempts, 23 (85.2%) were because of the presence
      of significant thrombus within the filter and 4 (14.8%) were because of tilting
      and strut perforation. Of the 23 filters containing significant thrombus, 9
      (39.1%) were later retrieved after a period of anticoagulation and resolution of
      the thrombus. CONCLUSIONS: Retrievable IVC filters can be removed with a high
      degree of success. Approximately one in ten retrievable IVC filter removal
      attempts may fail initially, usually because of significant thrombus within the
      filter. This does not preclude possible removal at a later date.

PMID- 25367647
TI  - Prioritizing barriers to successful implementation of hospital information
      systems.
AB  - Hospital information systems (HIS) are often implemented to enhance the quality
      of care, as well as to improve the efficiency and safety of health care services.
      However, there are various barriers for their successful implementation. The aim
      of this paper is to prioritize these barriers. This research is a cross sectional
      analytic-descriptive study. The study populations were hospital managers, IT
      department administrators, and clinical supervisors at the academic and non
      academic hospitals of two cities in Iran. The data was collected by a
      questionnaire that its content validity was confirmed by three specialists. Its
      reliability was confirmed using Cronbach's alpha (alpha = 0.78). Questionnaire
      contained five dimensions and 39 implementation barriers. The collected data was
      analyzed by descriptive and analytical statistics using the Kendall Rank
      Correlation Coefficient and Chi2 tests. The findings of the study revealed that
      lack of powerful information networks, error in data entry, technical problems
      related to system design, lack of organizational training, lack of users'
      knowledge about system and working with it, and negative attitudes of providers
      and patients toward systems are the most important barriers of HIS
      implementation. Prioritizing of these barriers helps policy makers to decide what
      to do when planning for HIS utilization.

PMID- 25367648
TI  - Risk factors: Women living near to a road at increased risk of sudden cardiac
      death.

PMID- 25367649
TI  - Macrophage subsets in atherosclerosis.
AB  - Macrophage accumulation within the vascular wall is a hallmark of
      atherosclerosis. In atherosclerotic lesions, macrophages respond to various
      environmental stimuli, such as modified lipids, cytokines, and senescent
      erythrocytes, which can modify their functional phenotypes. The results of
      studies on human atherosclerotic plaques demonstrate that the relative
      proportions of macrophage subsets within a plaque might be a better indicator of
      plaque phenotype and stability than the total number of macrophages.
      Understanding the function of specific macrophage subsets and their contribution
      to the composition and growth of atherosclerotic plaques would aid the
      identification of novel strategies to delay or halt the development of the
      disease and its associated pathophysiological consequences. However, most studies
      aimed at characterizing the phenotypes of human macrophages are performed in
      vitro and, therefore, their functional relevance to human pathology remains
      uncertain. In this Review, the diverse range of macrophage phenotypes in
      atherosclerotic lesions and their potential roles in both plaque progression and
      stability are discussed, with an emphasis on human pathology. 

PMID- 25367650
TI  - Stem cells: BMMC treatment safe but not an improvement on standard therapy.

PMID- 25367651
TI  - Atherosclerosis: Carotid artery stenting versus endarterectomy--no difference in
      long-term outcomes.

PMID- 25367653
TI  - The relationship of age, function, and psychological distress in multiple
      sclerosis.
AB  - Age is related to less distress in several populations including people with
      multiple sclerosis (MS). One theory posits this is due to decreased emotional
      reactivity and better coping as people age and we attempted to test this theory
      in MS. We used a cross-sectional survey of 429 people with MS. Participants
      completed measures of physical and cognitive function, depressive symptoms and
      anxiety. Age moderated the relationship of physical function to distress, such
      that decreased physical function was related to more distress in younger
      participants. Age moderated the relationship of cognitive function to depression,
      such that decreased cognitive function was related to more depressive symptoms in
      younger participants. Age did not moderate the relationship of cognitive function
      and anxiety. The effect was only seen in women with MS; however, there were fewer
      men in the sample. The results are consistent with the theory of decreased
      emotional reactivity and better coping with age. However, we were unable to test
      this in much older adults (75+ years of age). 

PMID- 25367652
TI  - Balancing ischaemia and bleeding risks with novel oral anticoagulants.
AB  - Vitamin K antagonists (VKAs) have long been the standard of care for treatment of
      venous thromboembolism (VTE), and thromboprophylaxis in atrial fibrillation (AF).
      Despite their efficacy, their use requires frequent monitoring and is complicated
      by drug-drug interactions and the need to maintain a narrow therapeutic window.
      Since 2009, novel oral anticoagulants (NOACs), including the direct thrombin
      inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and
      rivaroxaban, have become alternative options to VKAs owing to their predictable
      and safe pharmacological profiles. The overall clinical effect of these drugs,
      which is a balance between ischaemic benefit and bleeding harm, varies according
      to the clinical scenario. As adjunctive therapy to dual antiplatelet therapy in
      patients with acute coronary syndrome, NOACs are associated with incremental
      bleeding risks and modest benefits. For treatment of VTE, NOACs have a safer
      profile than VKAs and a similar efficacy. In thromboprophylaxis in AF, NOACs are
      associated with the greatest benefits by reducing both ischaemic events and
      haemorrhagic complications and might reduce mortality compared with VKAs. The
      role of NOACs continues to evolve as these drugs are evaluated in different
      patient populations, including those with renal impairment or with AF and
      undergoing percutaneous coronary intervention. 

PMID- 25367654
TI  - Estimation of hand-to-mouth transfer efficiency of lead.
AB  - There are currently no published empirical data that characterize hand-to-mouth
      transfer efficiencies for metallic lead. The purpose of this study was to
      quantify the hand-to-mouth transfer efficiency of lead in adult volunteers (n =
      6) using human saliva as a surrogate for the mouth and commercially available,
      100% lead fishing weights as the source of lead for dermal loading. Study
      volunteers' saliva was collected and subsequently poured onto a sheet of wax
      paper placed on a balance scale. The volunteers handled lead fishing weights with
      both hands for approximately 15 s and then pressed three fingers from the right
      hand (test hand) into their saliva 10 times, with ~0.45kg of pressure. The left
      hand (control hand) was used as a comparison for dermal loading of lead and had
      no contact with saliva. SKC Full Disclosure(r) wipes were used to collect lead
      from the saliva and skin surfaces. Samples were analyzed using the NIOSH 7300
      method, which was modified for wipes. The mean lead skin-to-saliva transfer
      efficiency was 24% (range: 12-34%). These data will be useful for more accurately
      characterizing lead hand-to-mouth transfer efficiencies and are likely to be
      helpful in exposure assessments or human health risk assessments. 

PMID- 25367655
TI  - Effects of big-five personality traits on the quality of relationship and
      satisfaction in Chinese coach-athlete dyads.
AB  - The present study examined the influence of personality traits on the quality of
      the Chinese coach-athlete relationship and satisfaction through a dyadic research
      design. A total of 350 coach-athlete dyads completed a self-report instrument
      that assessed personality traits, as well as perceptions of relationship quality
      and satisfaction with training. Results revealed that: (a) actor effects (i.e.,
      actor's personality will predict his or her own perceptions of relationship
      quality) of personality traits, namely, conscientiousness, extroversion, and
      neuroticism, on both coaches' and athletes' perceptions of relationship quality
      and (b) partner effects (an actor's own personality will predict his or her
      partner's perceptions of relationship quality) of only athletes' personality,
      namely, conscientiousness, extroversion, and neuroticism, on their coaches'
      perceptions of relationship quality. The findings suggested that each
      relationship member's personality trait contributed independently to relationship
      quality, and both actor and partner effects of the relationship quality on
      satisfaction with training were found to be significant. In Chinese sports
      culture, there presents a unique dynamics of personality and relationship quality
      among coach-athlete dyad. 

PMID- 25367656
TI  - The cancer genome atlas research network: a sight to behold.

PMID- 25367657
TI  - Occupational allergic contact dermatitis to chromium from cement: Estimating the
      size of the problem in Australia.
AB  - BACKGROUND: Allergic contact dermatitis (ACD) caused by chromium in cement is a
      significant occupational hazard. However, legislation in Europe over the past two
      decades to reduce the concentration of chromium in cement to <2 ppm through the
      addition of ferrous sulphate to cement, has seen a significant decrease in the
      incidence of chromium allergy. No such legislation exists in Australia. METHODS:
      A retrospective analysis of results from the Patchcams database of patients
      attending the Occupational Dermatology Clinic at the Skin & Cancer Foundation,
      Melbourne, who were patch tested for chromium between 1 January 1993 to 31
      December 2013, was conducted. RESULTS: Our review revealed that there has not
      been any significant change in the number of cases of ACD to chromium attributed
      to sensitisation through cement. Based on our data, we estimate that a minimum of
      24 cases of chromium occupational ACD (OACD) from cement is found in Australia
      yearly, causing considerable morbidity, often associated with an inability to
      work, costly workers' compensation claims and sometimes the development of the
      disabling condition, persistent post-occupational dermatitis. CONCLUSION: These
      findings highlight the need for high-level discussions about adopting European
      legislation in Australia in order to reduce the likelihood of developing chromium
      OACD from cement.

PMID- 25367659
TI  - Combination of psychodynamic psychotherapy and pharmacotherapy for patients with
      Personality Disorders: recent findings.

PMID- 25367658
TI  - Proteomics unravels extracellular vesicles as carriers of classical cytoplasmic
      proteins in Candida albicans.
AB  - The commensal fungus Candida albicans secretes a considerable number of proteins
      and, as in different fungal pathogens, extracellular vesicles (EVs) have also
      been observed. Our report contains the first proteomic analysis of EVs in C.
      albicans and a comparative proteomic study of the soluble secreted proteins. With
      this purpose, cell-free culture supernatants from C. albicans were separated into
      EVs and EV-free supernatant and analyzed by LC-MS/MS. A total of 96 proteins were
      identified including 75 and 61 proteins in EVs and EV-free supernatant,
      respectively. Out of these, 40 proteins were found in secretome by proteomic
      analysis for the first time. The soluble proteins were enriched in cell wall and
      secreted pathogenesis related proteins. Interestingly, more than 90% of these EV
      free supernatant proteins were classical secretory proteins with predicted N
      terminal signal peptide, whereas all the leaderless proteins involved in
      metabolism, including some moonlighting proteins, or in the exocytosis and
      endocytosis process were exclusively cargo of the EVs. We propose a model of the
      different mechanisms used by C. albicans secreted proteins to reach the
      extracellular medium. Furthermore, we tested the potential of the Bgl2 protein,
      identified in vesicles and EV-free supernatant, to protect against a systemic
      candidiasis in a murine model. 

PMID- 25367660
TI  - Constraint and loneliness in agoraphobia: an empirical investigation.
AB  - While progress in the aetiopathology and treatment of panic disorder is
      indisputable, research regarding agoraphobia lacks behind. One significant-yet
      untested- theory by Guidano and Liotti, suggests the existence of inner
      representations of fear of "constraint" and fear of "loneliness" as two major
      schemata, important in the pathogenesis and manifestation of agoraphobia.
      Activation of these schemata may occur in situations in which the patient: (a)
      feels as in an inescapable trap (constraint) or (b) alone, unprotected and
      helpless (loneliness). Upon activation, the "constraint" schema elicits such
      symptoms as asphyxiation, chest pain, difficult breathing, motor agitation and
      muscular tension, while the "loneliness" schema elicits such symptoms as
      sensation of tachycardia, weakness of limbs, trembling or fainting. Activation of
      these schemata by content-compatible stimuli is expected to trigger various, yet
      distinct, response patterns, both of which are indiscriminately described within
      the term "agoraphobia". In order to investigate this hypothesis and its possible
      clinical applications, several mental and physical probes were applied to 20
      patients suffering primarily from agoraphobia, and their responses and
      performance were recorded. Subjects also completed the "10-item Agoraphobia
      Questionnaire" prepared by our team aiming at assessing cognitions related to
      Guidano and Liotti's notion of "loneliness" and "constraint". Breath holding (BH)
      and Hyperventilation (HV) were selected as physical probes. BH was selected as an
      easily administered hypercapnea - induced clinical procedure, because of its
      apparent resemblance to the concept of "constraint". Subjects were instructed to
      hold their breath for as long as they could and stop at will. Similarly, it was
      hypothesized that HV might represent a physical "loneliness" probe, since it can
      elicit such symptoms as dizziness, paraesthesias, stiff muscles, cold hands or
      feet and trembling, reminiscent of a "collapsing type" symptomatology. Patients'
      responses and performance were recorded by visual analogue scales and heart rate
      and respiratory rhythm were being registered continuously. Although the overall
      elicited symptoms were not differentiated in a meaningful way, a significant
      correlation was registered between duration of physical probes and scoring of the
      "10-item Agoraphobia Questionnaire". Duration of BH was inversely correlated (r=
      0.456, p <0.05) with the score of the 5 "constraint-type" agoraphobic items while
      duration of HV was inversely correlated (r=-0.479, p <0.03) with the score of the
      5 "lonelinesstype" agoraphobic items. Assuming that our questionnaire taped the
      "loneliness" and "constraint" schema threat, our hypothesis derived from Guidano
      & Liotti's assumptions was partially confirmed. 

PMID- 25367661
TI  - Agomelatine augmentation in obsessive compulsive disorder: a preliminary report.
AB  - Obsessive-compulsive disorder (OCD) is often the anxiety disorder that affects
      approximately 2% of the population. This disorder is associated with significant
      morbidity and dysfunction, and is included in the World Health Organization list
      of the ten most disabling medical illnesses. The therapeutic response of patients
      with OCD is relatively poor compared with that of other mental disorders.
      Pharmacological interventions for OCD have focused on modulating primarily
      serotonin function and secondarily dopamine neurotransmission. Augmentation
      treatment has been the subject of several studies in treatment-resistant
      obsessive compulsive disorder (OCD). We hypothesized that medications with a dual
      action on the melatoninergic and serotoninergic systems may be of use in
      treatment-resistant OCD. In this open label study we investigated the efficacy
      and safety of agomelatine augmentation in treatment-resistant OCD. Twelve
      patients, aged 18-50, fulfilling OCD criteria, having failed to respond to
      adequate treatment with a Serotonine Reuptake Inhibitor for at least 16 weeks,
      were assigned to receive agomelatine augmentation. Subjects were assessed with
      the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and were screened for
      treatment-emergent side effects at baseline and week 16 of treatment. We excluded
      patients with comorbid psychopathology, serious medical comorbidity, current or
      past history of substance abuse and severe personality disorders as well as
      patients receiving psychotherapy in addition to psychopharmacological treatment.
      Agomelatine augmentation lead to net improvement in Y-BOCS and its obsession and
      compulsion subscales after 16 weeks of treatment (all p<0.005). Agomelatine
      augmentation was well-tolerated and none of the patients dropped-out. Treatment
      related adverse events were recorded as follows: (n, %): nausea: 1 (8.3%),
      headache 4 (33.3%), dizziness: 3 (25%) and somnolence: 2 (16.7%). The present
      case series study has several limitations due to its open-label design and the
      absence of a placebo or active control group. The small number of patients
      further limits the impact of our findings. The present case series study showed
      that a 16 week add-on treatment with agomelatine, achieved on average a 25%
      improvement in Y-BOCS in refractory to treatment OCD patients; side effects were
      mild, and none of the patients dropped out throughout the 16-week study period.
      Agomelatine could be efficacious and well tolerated as an augmenting agent in
      refractory to treatment OCD. The unique pharmacological profile of agomelatine
      and its dual action on serotoninergic and melatoninergic receptors may be of
      interest in this difficult-to-treat illness. Further controlled studies are
      warranted to explore the efficacy of agomelatine, as well as the potential role
      of circadian rhythm modulation both in the pathophysiology and treatment of OCD. 

PMID- 25367662
TI  - Child is father of the man: child abuse and development of future
      psychopathology.
AB  - Available epidemiological data indicate that the abuse of children within
      families is a very common phenomenon, and is still on the rise. Among others,
      abuse includes direct physical and emotional violence to the child, as well as
      the indirect emotional trauma of witnessing interparental violence. These early
      trauma experienced within the context of the family can influence the development
      of the child's personality as well as predispose towards the development of
      mental disorders in adulthood. There are some important factors influencing the
      occurrence of abuse, or the conditions predisposing it: certain parental
      personality traits appear to be instrumental, and the presence of individual
      psychopathology of parents is also connected with different forms of family
      dysfunction as a system, representing a variable which is interpolated in the
      quality of parenthood as the most important factor that determines long-term
      consequences on children and possible future psychopathology. The complex but
      tangible effects of parents' personality traits on the psychological development
      of children may contribute to the transgenerational transmission of abuse and
      violence. The phenomenon of domestic violence and abuse can be described from the
      perspective of the psychological and systemic theoretical postulates. According
      to systemic theory and practice, dysfunctional communication in the family is a
      significant predictor for domestic violence. Characteristics of dysfunctional
      communication include low levels of verbal expressiveness and emotional
      responsiveness, low tolerance to criticism and its interpretation as a threat or
      intimidation, and consequently increased anxiety and subsequent escalation of an
      argument into violence. Overall it seems that there may be a complex connection
      between parental personality and family interaction patterns, leading to
      dysfunctional communication which further amplifies the detrimental
      characteristics of family dynamics, and eventually escalates to violence.
      According to one theory, there may be a degree of transgenerational transmission
      of these communication patterns in children who have been victims of violence,
      thus propagating the conditions for violence, this time perpetrated by the
      victims themselves. Therefore there is a pressing need for prevention, perhaps
      through psychoeducation for parents or through early detection and treatment of
      traumatized children and adolescents, in the hope that the transgenerational
      vicious cycle of violence may be broken. 

PMID- 25367663
TI  - Pseudologia fantastica a deux: review and case study.
AB  - While lying is a diachronic integral part of human interaction, pseudologia
      fantastica represents probably its psychopathological dimension. There are
      relatively few reported cases on psychological mechanisms of pathological lying
      and also on criteria concerning psychopathological development on a ground of
      lying. A review of literature on possible psychological mechanisms of pseudologia
      fantastica is presented. Psychopathological qualities are rather controversial,
      especially whether pathological lying is a conscious act or not. DSM IV-TR
      recognizes pseudologia fantastica in association with factitious disorder but not
      as a clinical entity. Diagnostic issues are raised regarding lying, deception,
      pseudology and its shared dimension. Cases of shared pseudology are rarely
      reported in literature. Related shared psychopathological phenomena such as
      pseudologia a deux, folie a deux and mass hysteria are equally examined and
      compared under the prism of 'mental infection'. Cases of pseudologia fantastica
      are poorly understood or underecognized and clinicians usually pay minor
      attention in its psychopathological significance. It remains doubtful, whether
      pathological lying should be considered as an autonomous clinical entity. The
      need for research both on phenomenology and pathophysiology is emphasized. In
      addition to reviewing literature, we also report a case of pseudology a deux in a
      couple, a female and a male patient. Presented psychopathological manifestations,
      personality characteristics, psychological and social factors concerning both
      patients are considered, aiming to determine a sufficient phenomenological
      analysis. The diagnoses of pseudologia fantastica and folie a deux are discussed
      and documented. A second axis diagnosis of personality disorder and other
      diagnostic issues are also considered. A favorable issue of this case, within a
      follow up of one year, is due to the therapeutic and social potential of a
      community psychiatry's setting, offering an individual follow up to both partners
      and a family approach including the ex husband of the female patient and her two
      minor children. The presented case focuses on a notably rare and controversial
      form of pathological lying, pseudologia fantastica a deux, and possible
      underlying mechanisms. 

PMID- 25367664
TI  - Suicide in ancient Greece.
AB  - The theme of suicide appears several times in ancient Greek literature. However,
      each such reference acquires special significance depending on the field from
      which it originates. Most of the information found in mythology, but the suicide
      in a mythological tale, although in terms of motivation and mental situation of
      heroes may be in imitation of similar incidents of real life, in fact is linked
      with the principles of the ancient Greek religion. In ancient drama and mainly in
      tragedies suicide conduces to the tragic hypostasis of the heroes and to the
      evolution of the plot and also is a tool in order to be presented the ideas of
      poets for the relations of the gods, the relation among gods and men and the
      relation among the men. In ancient Greek philosophy there were the deniers of
      suicide, who were more concerned about the impact of suicide on society and also
      these who accepted it, recognizing the right of the individual to put an end to
      his life, in order to avoid personal misfortunes. Real suicides will be found
      mostly from historical sources, but most of them concern leading figures of the
      ancient world. Closer to the problem of suicide in the everyday life of antiquity
      are ancient Greek medicines, who studied the phenomenon more general without
      references to specific incidents. Doctors did not approve in principal the
      suicide and dealt with it as insane behavior in the development of the mental
      diseases, of melancholia and mania. They considered that the discrepancy of
      humors in the organ of logic in the human body will cause malfunction, which will
      lead to the absurdity and consequently to suicide, either due to excessive
      concentration of black bile in melancholia or due to yellow bile in mania. They
      believed that greater risk to commit suicide had women, young people and the
      elderly. As therapy they used the drugs of their time with the intention to
      induce calm and repression in the ill person, therefore they mainly used
      mandragora. In general, we would say that there were many reasons to suicide
      someone in antiquity. Very important factor was to avoid captivity and the
      consequent overcrowding of indignity, especially for politicians and military
      leaders. Also intention in these circumstances was to avoid torture and the
      disgrace of rape. Strong grief is another reason, as in case of death of family
      members. The erotic disappointment had place in ancient suicides, which concerned
      both men and women, while there were also suicide for financial reasons.
      Especially for the elderly, the despair of the anility in conjunction with
      physical illness and cachexia, were important factors for these people to decide
      thee suicidal. Finally, the methods of suicide fitted their epoch, but bear
      resemblance to those of the modern time. Poisoning was very common to both men
      and women but equally popular in both sexes was also the hanging. It was not
      unusual to fall from a high in order to reach the death, while stabbing a sword
      in the body for self killing was widespread in men and soldiers. 

PMID- 25367665
TI  - Alcohol misuse in Greece: a 15-year experience from a specialized outpatient
      service.
AB  - Alcohol use in Greece is traditionally diffused among its population. According
      to general population surveys, three out of four Greeks aged 12-64 referred to
      alcohol consumption during the last year and 10% reported at least one episode of
      alcohol abuse during the last month. Furthermore, the large majority of young
      people aged 13-18 reported lifetime use of alcohol and 14.8% of them reported
      more than three episodes of alcohol abuse during the last month. Apparently,
      cultural factors have influenced the pattern of alcohol consumption and the
      ensuing alcohol-related problems during the last two decades. The "Athena"
      Service is an outpatient therapeutic unit for the management of substance
      misusers and their families. It is a specialized abstinence-oriented service that
      does not administer substance substitutes; mental health professionals of the
      service work as a multidisciplinary team. Motivational approaches, individual
      cognitive-behavioural psychotherapy and family interventions of a systemic
      orientation are the principal therapeutic techniques applied. Adjunctive
      medication is prescribed whenever mild to moderate concomitant psychopathology is
      detected. Support measures such as provisional use of medication, use of
      antagonistic agents or brief hospitalization can be provided if deemed necessary.
      No strict time limits are applied regarding treatment duration and discharge from
      the program. During the period 1998-2013, a total of 1511 individuals with
      alcohol-related problems addressed the service. The changing pattern of substance
      misuse over the last fifteen years can be summarized as follows: (a) there is a
      gradually increasing number of women misusing substances; (b) there is an
      increasing proportion of young adults reporting multi-substance use with
      concurrent psychiatric disorders; (c) there is an increasing proportion of young
      adults regularly using/misusing substances; (d) there is a decreasing proportion
      of middle-aged individuals presenting with chronic alcohol misuse and dependence,
      with a long-ago onset and slow development of alcohol-related problems; and (e)
      the proportion of older age individuals presenting chronic alcohol misuse and
      dependence with concurrent severe neurological impairments is increasing. Also,
      detailed information on a sample of 133 individuals who addressed the service for
      alcohol-related problems during 2012 is given and further discussed. Finally, the
      need for close monitoring of dangerous alcohol consumption and changing patterns
      of misuse in times of socio-economic crisis, alongside with an increasing need to
      provide treatment, is highlighted. 

PMID- 25367666
TI  - Pharmacoresistant partial-onset epilepsy misdiagnosed as panic disorder: a case
      report.
AB  - The clinical differentiation between simple partial epileptic seizures of
      temporal lobe origin and panic attacks is often difficult on clinical grounds
      alone, because both conditions are characterized by common symptomatology which
      includes the feeling of fear, autonomic system dysfunction, disorientation and
      alternation of the level of consciousness when these conditions evolve
      clinically. The symptoms stem from common pathophysiologic and anatomic
      substrates of these two conditions, localized in the limbic system, especially
      the amygdala. We present the case of a young woman who had a febrile seizure in
      childhood and subsequent episodes of fear accompanied by tremor and possible
      alteration of consciousness followed by headache. These spells were diagnosed as
      panic attacks during her teenage years and she was given Clobazam in order to
      suppress them. The patient responded well for several years without attacks but
      her symptoms reappeared following discontinuation of her medication in order to
      conceive. At that time a detailed history was taken from her spouse and further
      clinical evaluation raised the suspicion of seizures especially due to the fact
      that her spells were characterized by alteration of consciousness; she was
      therefore referred for additional investigations which included admission to a
      monitoring unit for epilepsy. Long-term video-EEG recording revealed the presence
      of simple partial seizures with secondary generalization confirming the clinical
      impression. She was subsequently treated with antiepileptic medications; however
      the patient's condition worsened to the point where she became pharmacoresistant
      having failed several antiepileptic drug trials in monotherapy or combination. An
      MRI scan of the brain revealed the presence of right-sided mesial temporal
      sclerosis, a known consequence of febrile seizures. Her seizures were nocturnal
      tonic-clonic and gradually worsened to the point of occurring during most nights.
      She was therefore referred for a presurgical evaluation which confirmed that the
      epileptic focus was associated with the area of mesial temporal sclerosis. The
      epileptic focus was successfully removed from the right anterior temporal lobe
      and since then she remained free of seizures whereas, in addition, the presumed
      symptoms of panic attacks also resolved. This case indicates the occasional
      difficulty in diagnosing simple partial seizures and how it may be confused with
      psychiatric conditions. Therefore, the treating physician, especially the
      psychiatrist, should remain vigilant when treating cases of panic attacks,
      especially when they present with either atypical symptomatology, such as the
      case described, or when they do not respond to appropriately chosen treatment;
      such cases may warrant referral for further investigation. 

PMID- 25367667
TI  - Intestinal biomechanics simulator for robotic capsule endoscope validation.
AB  - This work describes the development and validation of a novel device which
      simulates important forces experienced by Robotic Capsule Endoscopes (RCE) in
      vivo in the small intestine. The purpose of the device is to expedite and lower
      the cost of RCE development. Currently, there is no accurate in vitro test method
      nor apparatus to validate new RCE designs; therefore, RCEs are tested in vivo at
      a cost of ~$1400 per swine test. The authors have developed an in vitro RCE
      testing device which generates two peristaltic waves to accurately simulate the
      two biomechanical actions of the human small intestine that are most relevant to
      RCE locomotion: traction force and contact force. The device was successfully
      calibrated to match human physiological ranges for traction force (4-40 gf),
      contact force (80-500 gf) and peristaltic wave propagation speed (0.08-2 cm s(
      1)) for a common RCE capsule geometry of 3.5 cm length and 1.5 cm diameter.

PMID- 25367668
TI  - Development, validation, and use of a semi-quantitative food frequency
      questionnaire for assessing protein intake in Papua New Guinean Highlanders.
AB  - OBJECTIVES: The aim of this article was to develop a semi-quantitative food
      frequency questionnaire (FFQ) and evaluate its validity to estimate habitual
      protein intake, and investigate current dietary protein intakes of Papua New
      Guinea (PNG) Highlanders. METHODS: A 32-item FFQ was developed and tested among
      135 healthy male and female volunteers. The FFQ-estimated daily total and animal
      protein intakes were compared with biomarkers and 3-day Weighed Food Records
      (WFR) by correlation analyses, Bland-Altman plot analyses and joint
      classification analyses. RESULTS: The FFQ-estimated total protein intake
      significantly correlated with urinary nitrogen in the first morning void after
      adjusting urinary creatinine concentration (r = 0.28, P < 0.01) and the FFQ
      estimated animal protein intake significantly correlated with the hair delta(15)
      N (Spearman's r = 0.34, P < 0.001). The limits of agreement were +/-2.39 Z-score
      residuals for total protein intake and +/-2.19 Z-score for animal protein intake,
      and intra-individual differences increased as protein intake increased. The
      classification into the same and adjacent quartiles was 66.0% for total protein
      intake and 73.6% for animal protein intake. Median daily total and animal protein
      intake estimates from the FFQ and the 3-day WFR showed a good agreement with
      differences of 0.2 and 4.9 g, respectively. None of the studied communities in
      the PNG Highlands met the biologically required protein intake; although the
      community closer to an urban center showed higher protein intake than the more
      remote communities. CONCLUSIONS: The newly developed 32-item FFQ for PNG
      Highlanders is applicable for evaluation of protein intake at the individual
      level. Am. J. Hum. Biol. 27:349-357, 2015. (c) 2014 Wiley Periodicals, Inc.

PMID- 25367669
TI  - The structural basis of DNA binding by the single-stranded DNA-binding protein
      from Sulfolobus solfataricus.
AB  - Canonical single-stranded DNA-binding proteins (SSBs) from the
      oligosaccharide/oligonucleotide-binding (OB) domain family are present in all
      known organisms and are critical for DNA replication, recombination and repair.
      The SSB from the hyperthermophilic crenarchaeote Sulfolobus solfataricus (SsoSSB)
      has a 'simple' domain organization consisting of a single DNA-binding OB fold
      coupled to a flexible C-terminal tail, in contrast with other SSBs in this family
      that incorporate up to four OB domains. Despite the large differences in the
      domain organization within the SSB family, the structure of the OB domain is
      remarkably similar all cellular life forms. However, there are significant
      differences in the molecular mechanism of ssDNA binding. We have determined the
      structure of the SsoSSB OB domain bound to ssDNA by NMR spectroscopy. We reveal
      that ssDNA recognition is modulated by base-stacking of three key aromatic
      residues, in contrast with the OB domains of human RPA and the recently
      discovered human homologue of SsoSSB, hSSB1. We also demonstrate that SsoSSB
      binds ssDNA with a footprint of five bases and with a defined binding polarity.
      These data elucidate the structural basis of DNA binding and shed light on the
      molecular mechanism by which these 'simple' SSBs interact with ssDNA. 

PMID- 25367670
TI  - Transmission of H7N9 influenza virus in mice by different infective routes.
AB  - BACKGROUND: On 19 February 2013, the first patient infected with a novel
      influenza A H7N9 virus from an avian source showed symptoms of sickness. More
      than 349 laboratory-confirmed cases and 109 deaths have been reported in mainland
      China since then. Laboratory-confirmed, human-to-human H7N9 virus transmission
      has not been documented between individuals having close contact; however, this
      transmission route could not be excluded for three families. To control the
      spread of the avian influenza H7N9 virus, we must better understand its
      pathogenesis, transmissibility, and transmission routes in mammals. Studies have
      shown that this particular virus is transmitted by aerosols among ferrets.
      METHODS: To study potential transmission routes in animals with direct or close
      contact to other animals, we investigated these factors in a murine model.
      RESULTS: Viable H7N9 avian influenza virus was detected in the upper and lower
      respiratory tracts, intestine, and brain of model mice. The virus was
      transmissible between mice in close contact, with a higher concentration of virus
      found in pharyngeal and ocular secretions, and feces. All these biological
      materials were contagious for naive mice. CONCLUSIONS: Our results suggest that
      the possible transmission routes for the H7N9 influenza virus were through
      mucosal secretions and feces.

PMID- 25367671
TI  - Benign soft-tissue lesions of the fingers: radiopathological correlation and
      clinical considerations.
AB  - Soft-tissue lesions of the fingers are commonly found in daily clinical practice.
      A wide range of tumors and pseudotumors have been described in this location, and
      the majority of them are benign. Ganglion cysts are the most common entity, and
      the localized type of tenosynovial giant cell tumors are the most frequent solid
      condition. Both may be easily recognized owing to their typical clinical and
      radiological characteristics. However, categorization of the spectrum of soft
      tissue lesions of the fingers remains limited, despite imaging development, and
      many patients undergo surgery before radiological or histological diagnosis.
      Clinical history, radiographic features, and ultrasound and magnetic resonance
      patterns may help in obtaining the correct diagnosis or reducing the list of
      differential diagnoses. Radiologists should be familiar with imaging findings so
      that they can determine the size, extension, and affected neighboring anatomical
      structures, and provide information that allows adequate presurgical counseling. 

PMID- 25367672
TI  - Intra-individual assessment of inflammatory severity and cartilage composition of
      finger joints in rheumatoid arthritis.
AB  - OBJECTIVE: To intra-individually assess the association of inflammation severity
      and cartilage composition measured by RAMRIS synovitis sub-score and delayed
      gadolinium-enhanced magnetic resonance imaging of the cartilage (dGEMRIC) of
      metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA).
      METHODS: Forty-three patients with RA according to ACR/EULAR classification
      criteria (age 52.9 +/- 14.5 years, range, 18-77 years) were included in this
      study. All study participants received 3-T MRI scans of the metacarpophalangeal
      joints of the second and third finger (MCP 2 and 3). The severity of synovitis
      was scored according to the RAMRIS synovitis sub-score by two readers in
      consensus. In the cases with identical synovitis sub-scores, two radiologists
      decided in consensus on the joint with more severe synovitis. Cartilage
      composition was assessed with dGEMRIC. To test the association of inflammation
      severity and cartilage damage and in order to eliminate inter-patient
      confounders, each patient's MCP 2 and 3 were dichotomized into the joint with
      more severe synovitis versus the joint with less severe synovitis for a paired
      Wilcoxon test of dGEMRIC value. RESULTS: There was a significant difference of
      dGEMRIC value (median of difference: 47.12, CI [16.6; 62.76]) between the
      dichotomized MCPs (p = 0.0001). There was a significant correlation between
      dGEMRIC value and RAMRIS synovitis grading of the joint with more severe
      synovitis (r = 0.5; p < 0.05) and the joint with less severe synovitis (r = 0.33;
      p < 0.05). CONCLUSIONS: Our data concur with the concept that synovitis severity
      is associated with cartilage damage. The local inflammatory status on a joint
      level correlated significantly with the extent of cartilage degradation in
      biochemical MRI.

PMID- 25367673
TI  - Loehlin's original models and model contributions.
AB  - This is a short story about John C. Loehlin who is now at the University of Texas
      at Austin, dealing with his original simulation models and developments, which
      led to his current latent variable models. This talk was initially presented at a
      special meeting for John before the BGA in Rhode Island, and I was very pleased
      to contribute. It probably goes without saying, but John helped create this
      important society, has been a key contributor to this journal for several
      decades, and he deserves a lot for this leadership.

PMID- 25367674
TI  - An integrated microspectrometer for localised multiplexing measurements.
AB  - We describe the development of an integrated lensed Arrayed Waveguide Grating
      (AWG) microspectrometer for localized multiplexing fluorescence measurements. The
      device, which has a footprint that is only 1 mm wide and 1 cm long, is capable of
      spectroscopic measurements on chip. Multiple fluorescence signals were measured
      simultaneously based upon simple intensity readouts from a CCD camera. We also
      demonstrate the integration of the AWG spectrometer with a microfluidic platform
      using a lensing function to confine the beam shape for focused illumination. This
      capability enhances signal collection, gives better spatial resolution, and
      provides a route for the analysis of small volume samples (e.g. cells) in flow.
      To show these capabilities we developed a novel "bead-AWG" platform with which we
      demonstrate localized multiplexed fluorescence detection either simultaneously or
      successively. Such an integrated system provides the basis for a portable system
      capable of optical detection of multi-wavelength fluorescence from a single
      defined location. 

PMID- 25367675
TI  - Validity and reliability of stillbirth data using linked self-reported and
      administrative datasets.
AB  - BACKGROUND: A high rate of stillbirth was previously observed in the Australian
      Longitudinal Study of Women's Health (ALSWH). Our primary objective was to test
      the validity and reliability of self-reported stillbirth data linked to state
      based administrative datasets. METHODS: Self-reported data, collected as part of
      the ALSWH cohort born in 1973-1978, were linked to three administrative datasets
      for women in New South Wales, Australia (n = 4374): the Midwives Data Collection;
      Admitted Patient Data Collection; and Perinatal Death Review Database. Linkages
      were obtained from the Centre for Health Record Linkage for the period 1996-2009.
      True cases of stillbirth were defined by being consistently recorded in two or
      more independent data sources. Sensitivity, specificity, positive predictive
      value, negative predictive value, percent agreement, and kappa statistics were
      calculated for each dataset. RESULTS: Forty-nine women reported 53 stillbirths.
      No dataset was 100% accurate. The administrative datasets performed better than
      self-reported data, with high accuracy and agreement. Self-reported data showed
      high sensitivity (100%) but low specificity (30%), meaning women who had a
      stillbirth always reported it, but there was also over-reporting of stillbirths.
      About half of the misreported cases in the ALSWH were able to be removed by
      identifying inconsistencies in longitudinal data. CONCLUSIONS: Data linkage
      provides great opportunity to assess the validity and reliability of self
      reported study data. Conversely, self-reported study data can help to resolve
      inconsistencies in administrative datasets. Quantifying the strengths and
      limitations of both self-reported and administrative data can improve
      epidemiological research, especially by guiding methods and interpretation of
      findings.

PMID- 25367676
TI  - Sensitivity and specificity of automated detection of early repolarization in
      standard 12-lead electrocardiography.
AB  - BACKGROUND: Early repolarization (ER) is defined as an elevation of the QRS-ST
      junction in at least two inferior or lateral leads of the standard 12-lead
      electrocardiogram (ECG). Our purpose was to create an algorithm for the automated
      detection and classification of ER. METHODS: A total of 6,047 electrocardiograms
      were manually graded for ER by two experienced readers. The automated detection
      of ER was based on quantification of the characteristic slurring or notching in
      ER-positive leads. The ER detection algorithm was tested and its results were
      compared with manual grading, which served as the reference. RESULTS: Readers
      graded 183 ECGs (3.0%) as ER positive, of which the algorithm detected 176
      recordings, resulting in sensitivity of 96.2%. Of the 5,864 ER-negative
      recordings, the algorithm classified 5,281 as negative, resulting in 90.1%
      specificity. Positive and negative predictive values for the algorithm were 23.2%
      and 99.9%, respectively, and its accuracy was 90.2%. Inferior ER was correctly
      detected in 84.6% and lateral ER in 98.6% of the cases. CONCLUSIONS: As the
      automatic algorithm has high sensitivity, it could be used as a prescreening tool
      for ER; only the electrocardiograms graded positive by the algorithm would be
      reviewed manually. This would reduce the need for manual labor by 90%.

PMID- 25367677
TI  - Preventing malaria in international travellers: an evaluation of published
      English-language guidelines.
AB  - BACKGROUND: People intending to travel may seek information on malaria prevention
      from a range of sources. To ensure the best protection, this information needs to
      be reliable, up-to-date, consistent, and useful to their decision making. This
      study appraises current international and national guidelines written in English
      for malaria prevention in travellers, and whether any recommendations conflict.
      METHODS: We systematically identified national or international English-language
      guidelines on malaria prevention in travellers to July 2013 using standard and
      multiple searching methods. We critically appraised guidelines using the AGREE II
      tool, and report inconsistent recommendations within guidelines. RESULTS: We
      identified five sets of English-language guidelines on preventing malaria for
      travellers. Assessment against AGREE II indicate that all of the guidelines fall
      short of internationally accepted standards in guideline development: none
      include a transparent description of methods; only one describes sources of
      funding or potential conflicts of interest; and only one includes formal
      presentation of the evidence alongside transparent assessment of the quality of
      that evidence. There were a number of important discrepancies between guidelines,
      and some omit information about effectiveness, safety and adverse effects of
      chemoprophylaxis options. CONCLUSIONS: The methods used for developing guidelines
      for malaria prevention in travellers lags behind current internationally
      recognized standards. Healthcare professionals as well as travellers themselves
      could be better informed if guidelines were more systematic and transparent
      summaries of the current knowledge on drug interventions in relation to effects,
      safety, administration and contra-indications.

PMID- 25367678
TI  - Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific
      mechanisms of innate immunity.
AB  - The immune system is implicated in a wide range of disorders affecting the brain
      and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a
      potent regulator of the innate immune system important for host defense but is
      also associated with injury and disease in the brain. Here, we show that IL-1 is
      a key mediator driving an innate immune response to inflammatory challenge in the
      mouse brain but is dispensable in extracerebral tissues including the lung and
      peritoneum. We also demonstrate that IL-1alpha is an important ligand
      contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS
      compartment (most likely microglia) is the major source driving this effect.
      These data reveal previously unknown tissue-specific requirements for IL-1 in
      driving innate immunity and suggest that IL-1-mediated inflammation in the brain
      could be selectively targeted without compromising systemic innate immune
      responses that are important for resistance to infection. This property could be
      exploited to mitigate injury- and disease-associated inflammation in the brain
      without increasing susceptibility to systemic infection, an important
      complication in several neurological disorders. 

PMID- 25367679
TI  - Thursday's child: the role of adverse childhood experiences in explaining mental
      health disparities among lesbian, gay, and bisexual U.S. adults.
AB  - This study examined how adverse childhood experiences (ACE) may explain
      disparities in poor mental health between lesbian, gay, and bisexual (LGB), and
      heterosexual adults. Data are from three US states' 2010 behavioral risk factor
      surveillance system surveys (n = 20,060) that included sexual orientation, ACE
      inventory, and mental distress. LGB status was significantly associated with
      mental distress (OR = 1.85 [1.14-3.02]). Once incorporating ACE scores into the
      multiple regression analysis, LGB status was no longer associated with mental
      distress (OR = 1.28 [0.76-2.16]). The results corroborate previous research that
      LGB individuals report greater prevalence of childhood adversity than their
      heterosexual peers, which may explain LGB adulthood health disparities. 

PMID- 25367680
TI  - Perceived barriers to mental health treatment among individuals with a past-year
      disorder onset: findings from a Canadian Population Health Survey.
AB  - PURPOSE: Despite the availability of efficacious treatments, few individuals with
      a new-onset mental disorder access treatment in a timely manner. While barriers
      to mental health treatment have been studied among prevalent cases, few studies
      have focused specifically on incident cases. The purpose of the current study was
      to examine the prevalence and correlates of perceived barriers to mental health
      treatment among incident cases. METHODS: Data came from the Canadian Community
      Health Survey, cycle 1.2 (CCHS 1.2), which represents a nationally representative
      sample of 36,984 Canadians. We used descriptive analyses to estimate the
      prevalence of different types of perceived barriers to treatment and logistic
      regression analyses to estimate the association between potential correlates and
      the probability of endorsing each type of barrier. RESULTS: The most frequently
      reported type of barrier was acceptability. Coping efficacy and psychological
      well-being were negatively associated with the likelihood of reporting
      accessibility barriers. Education was negatively associated with reporting
      acceptability barriers but positively associated with reporting availability
      barriers. CONCLUSIONS: Among individuals with a recent disorder onset,
      acceptability barriers are the most frequently reported. Perceived accessibility
      barriers may be open to influence from current clinical functioning and current
      perceptions of internal coping resources. These findings contribute to an
      important discussion about the complexity of pathways to care and point to the
      need for comprehensive approaches to overcoming barriers to care.

PMID- 25367681
TI  - Erratum to: Feelings of loneliness among adults with mental disorder.

PMID- 25367683
TI  - Characterization of the cultivable bacterial populations associated with field
      grown Brassica napus L.: an evaluation of sampling and isolation protocols.
AB  - Plant-associated bacteria are intensively investigated concerning their
      characteristics for plant growth promotion, biocontrol mechanisms and enhanced
      phytoremediation efficiency. To obtain endophytes, different sampling and
      isolation protocols are used although their representativeness is not always
      clearly demonstrated. The objective of this study was to acquire representative
      pictures of the cultivable bacterial root, stem and leaf communities for all
      Brassica napus L. individuals growing on the same field. For each plant organ,
      genotypic identifications of the endophytic communities were performed using
      three replicates. Root replicates were composed of three total root systems,
      whereas stem and leaf replicates needed to consist of six independent plant parts
      in order to be representative. Greater variations between replicates were found
      when considering phenotypic characteristics. Correspondence analysis revealed
      reliable phenotypic results for roots and even shoots, but less reliable ones for
      leaves. Additionally, realistic Shannon-Wiener biodiversity indices were
      calculated for all three organs and showed similar Evenness factors. Furthermore,
      it was striking that all replicates and thus the whole plant contained
      Pseudomonas and Bacillus strains although aboveground and belowground plant
      tissues differed in most dominant bacterial genera and characteristics. 

PMID- 25367682
TI  - Effects of chemical sanitization using NaOH on the properties of polysulfone and
      polyethersulfone ultrafiltration membranes.
AB  - Membranes used in bioprocessing applications are typically sanitized before use
      to insure aseptic operation. However, there is almost no information in the
      literature on the effects of this preuse sanitization step on the properties of
      the membrane. Experiments were performed with commercially available hollow fiber
      polysulfone (PSf) and polyethersulfone (PES) membranes with different nominal
      molecular weight cutoffs. Data were obtained for the membrane hydraulic
      permeability, dextran retention coefficients, zeta potential (surface charge),
      and extent of protein adsorption both before and after sanitization with 0.5 N
      NaOH at 45 degrees C for 30 min. Changes in chemical composition were examined
      using ATR-FT-IR and XPS. Sanitization caused a large increase in the net negative
      charge for all membranes. There was a small reduction in hydraulic permeability
      and a significant increase in dextran retention for the polyethersulfone
      membranes, consistent with a reduction in the effective pore size. Spectroscopic
      analyses suggest that this change is likely due to the base-catalyzed hydrolysis
      of the lactam ring in polyvinylpyrrolidone (PVP) that is typically is used as a
      wetting/pore-forming agent in PSf and PES membranes. Preuse sanitization also
      appeared to have a small effect on protein adsorption, although the extent of
      adsorption was quite low for both the virgin and sanitized membranes. The
      observed changes in membrane properties could have a significant impact on the
      ultrafiltration performance, demonstrating the importance of standardizing the
      sanitization procedures even in process development and scale-down validation
      studies.

PMID- 25367684
TI  - Dyskerin expression in human fetal, adult and neoplastic intrahepatic bile ducts:
      correlations with cholangiocarcinoma aggressiveness.
AB  - AIMS: To investigate the immunohistochemical expression of dyskerin, a biomarker
      involved in ribosome production and telomere maintenance, in human fetal, adult
      and neoplastic bile ducts, and possible correlations with cholangiocarcinoma
      aggressiveness. METHODS AND RESULTS: Sixty consecutive intrahepatic
      cholangiocarcinomas were collected and used for tissue microarray construction
      (total: 176 cores); clinical data and follow-up were also collected. Five fetal
      and 10 normal adult livers were included as controls. Automated
      immunohistochemistry for dyskerin, p53, and Ki67, and nucleolar silver staining,
      were performed. In normal livers, dyskerin expression was negative in smaller
      bile ducts (mean 44.8 MUm) and positive in bile ducts of larger diameter (mean
      116.1 MUm; P < 0.001). Expression was positive in 56.7% of cholangiocarcinomas,
      and correlated with p53 mutation (P = 0.008) and a higher proliferative (Ki67)
      index (P = 0.003), which were included as markers of tumour aggressiveness.
      Finally, dyskerin-positive cholangiocarcinomas showed a negative trend in disease
      free survival (P = 0.078) on univariate analysis. CONCLUSIONS: The non-neoplastic
      biliary tree seems to progressively lose dyskerin expression from the major
      branches to the peripheral portal bile ducts. Similarly, intrahepatic
      cholangiocarcinomas showed two patterns of dyskerin expression, and the dyskerin
      positive phenotype seemed to characterize more aggressive cholangiocarcinomas.

PMID- 25367685
TI  - Oxic microshield and local pH enhancement protects Zostera muelleri from sediment
      derived hydrogen sulphide.
AB  - Seagrass is constantly challenged with transporting sufficient O2 from above- to
      belowground tissue via aerenchyma in order to maintain aerobic metabolism and
      provide protection against phytotoxins. Electrochemical microsensors were used in
      combination with a custom-made experimental chamber to analyse the belowground
      biogeochemical microenvironment of Zostera muelleri under changing environmental
      conditions. Measurements revealed high radial O2 release of up to 500 nmol O2 cm(
      2) h(-1) from the base of the leaf sheath, maintaining a c. 300-MUm-wide plant
      mediated oxic microzone and thus protecting the vital meristematic regions of the
      rhizome from reduced phytotoxic metabolites such as hydrogen sulphide (H2S). H2S
      intrusion was prevented through passive diffusion of O2 to belowground tissue
      from leaf photosynthesis in light, as well as from the surrounding water column
      into the flow-exposed plant parts during darkness. Under water column hypoxia,
      high belowground H2S concentrations at the tissue surface correlated with the
      inability to sustain the protecting oxic microshield around the meristematic
      regions of the rhizome. We also found increased pH levels in the immediate
      rhizosphere of Z. muelleri, which may contribute to further detoxification of H2S
      through shifts in the chemical speciation of sulphide. Zostera muelleri can
      modify the geochemical conditions in its immediate rhizosphere, thereby reducing
      its exposure to H2S.

PMID- 25367686
TI  - Single versus combination tocolytic regimen in the prevention of preterm births
      in women: a prospective cohort study.
AB  - OBJECTIVE: Our objective is to compare the efficacy of combination regimen
      (salbutamol and nifedipine) against single regimen (nifedipine alone) in
      preventing preterm births among women with preterm labor. RESULTS: A total of 76
      women with gestational age (GA) ranging from 24+0 to 35+6 weeks, who sought
      treatment for preterm labor with or without cervical dilatation, were recruited
      for the prospective cohort study. Of these, 38 (50%) had single tocolytic regimen
      and 38 (50%) had combination tocolytic regimen. The mean GAs at admission were
      similar for both groups at 31 weeks (+/-2.93) for Group 1 and 30.9 weeks (+/
      2.88) for Group 2 (P=0.873). The mean GAs at delivery were 37.8 weeks (+/-1.98)
      for the single regimen and 36.2 weeks (+/-3.26) for the combined regimen
      (P=0.011). The mean tocolytic to delivery interval for the single regimen was
      longer at 6.74 weeks (+/-3.13) as compared with 5.21 weeks (+/-3.61) for the
      combination regimen (P<0.05). Those on the combination regimen complained of more
      adverse effects (P<0.001). CONCLUSION: Our study results suggested that the use
      of nifedipine as a single tocolytic regimen is as effective as the combination
      regimen in the delay of preterm births and has much less side effects. Hence, we
      recommend the sole use of nifedipine for the management of preterm labor.

PMID- 25367687
TI  - Fundamental principles of clinical and biochemical evaluation underlie the
      diagnosis and therapy of Cushing's syndrome.

PMID- 25367688
TI  - How early can one diagnose Cushing's disease? An early diagnosis in a case of
      prepubertal Cushing's disease.
AB  - BACKGROUND: Cushing's disease is very rare in children, and the diagnosis is
      frequently delayed by several years. OBJECTIVE: We report a case of prepubertal
      Cushing's disease with a medical history of only 9 months. This case illustrates
      the difficulties involved in diagnosing children at the early stage of the
      disease. CASE PRESENTATION: An 8-year-old prepubertal boy presented with rapid
      weight gain accompanied by a decreasing growth velocity and hirsutism. Thyroid
      function tests and growth factor levels were normal, thus excluding
      hypothyroidism and growth hormone deficiency. Cushing's syndrome was confirmed by
      elevated 24-h urinary free cortisol levels, increased diurnal cortisol levels,
      and a lack of cortisol suppression in the low-dose dexamethasone suppression
      test. Further tests to investigate the source of the hypercortisolism showed the
      following results: Basal morning adrenocorticotropic hormone (ACTH) was normal.
      The high-dose dexamethasone suppression test led to a 51% decrease in cortisol
      level. In the corticotropin-releasing hormone (CRH) test, ACTH and cortisol
      increased only by 28%. Repeated magnetic resonance imaging (MRI) finally revealed
      a microadenoma in the anterior pituitary, thus establishng the diagnosis of
      Cushing's disease. Upon diagnosis, the patient underwent transsphenoidal surgery.
      Histological analysis confirmed an ACTH-secreting pituitary adenoma. CONCLUSION:
      This case illustrates the difficulties associated with the clinical, biochemical,
      and radiological diagnoses of Cushing's disease in children. Early diagnosis
      remains a challenge because test results often do not match standard diagnostic
      criteria.

PMID- 25367689
TI  - Measures of pituitary gland and stalk: from neonate to adolescence.
AB  - OBJECTIVE: The aim of this study is to provide normative data about pituitary
      diameters in a pediatric population. Pituitary imaging is important for the
      evaluation of the hypothalamo-pituitary axis defect. However, data about normal
      pituitary gland diameters and stalk are limited, especially in children.
      Structure and the measurements of pituitary gland and pituitary stalk may change
      due to infection, inflammation, or neoplasia. METHODS: Among 14,854
      cranial/pituitary gland magnetic resonance imaging scans performed from 2011 to
      2013, 2755 images of Turkish children aged between 0 and 18 were acquired. After
      exclusions, 517 images were left. Four radiologists were educated by an
      experienced pediatric radiologist for the measurement and assessment of the
      pituitary gland and pituitary stalk. Twenty cases were measured by all
      radiologists for a pilot study and there was no interobserver variability.
      RESULTS: There were 10-22 children in each age group. The maximum median height
      of the pituitary gland was 8.48+/-1.08 and 6.19+/-0.88 mm for girls and boys,
      respectively. Volumes were also correlated with gender similar to height. Minimum
      median height was 3.91+/-0.75 mm for girls and 3.81+/-0.68 mm for boys. The
      maximum and minimum pituitary stalk basilar artery ratios for girls were 0.73+/
      0.12 and 0.59+/-0.10 mm. The ratios for boys were 0.70+/-0.12 and 0.56+/-0.11 mm.
      CONCLUSION: Our study demonstrated the pituitary gland and stalk size data of
      children in various age groups from newborn to adolescent. It is thought that
      these data can be applied in clinical practice. Future prospective follow-up
      studies with larger samples, which correlate the structural findings with the
      clinical and laboratory results are awaited.

PMID- 25367690
TI  - Effects of incivility in clinical practice settings on nursing student burnout.
AB  - AIMS: To examine the relationship between nursing students' exposure to various
      forms of incivility in acute care practice settings and their experience of
      burnout. BACKGROUND: Given that staff nurses and new nurse graduates are
      experiencing incivility and burnout in the workplace, it is plausible that
      nursing students share similar experiences in professional practice settings.
      DESIGN AND SAMPLE: A cross-sectional survey design was used to assess Year 4
      nursing students' (n=126) perceptions of their experiences of incivility and
      burnout in the clinical learning environment. METHODS: Students completed
      instruments to assess frequency of uncivil behaviors experienced during the past
      six months from nursing staff, clinical instructors, and other health
      professionals in the acute care practice setting and to measure student burnout.
      RESULTS: Reported incidences of incivility in the practice setting were related
      to burnout. Higher rates of incivility, particularly from staff nurses, were
      associated with higher levels of both components of burnout (emotional exhaustion
      and cynicism).

PMID- 25367691
TI  - Effect of rhubarb (Rheum emodi) in primary dysmenorrhoea: a single-blind
      randomized controlled trial.
AB  - BACKGROUND: The aim of this study was to investigate and evaluate the efficacy of
      Rheum emodi in the management of primary dysmenorrhoea. METHODS: A randomized,
      single-blind, standard controlled trial compared efficacy of R. emodi against
      mefenamic acid on diagnosed subjects of primary dysmenorrhoea for three
      consecutive cycles. Experimental group (n=30) received capsules of R. emodi
      powder two times a day, two days before the expected date of menstruation, and
      continued first three days of menstruation, while control group (n=15)
      participants received mefenamic acid capsules three times a day on the same
      protocol. The primary outcome measures were reduced in severity and duration of
      pain, assessed by visual analogue scale (VAS) and verbal multidimensional scoring
      system (VMSS), and secondary outcome measures were overall improvement of
      dysmenorrhoea and improved in quality of life (QOL). Statistical analysis was
      done by repeated measures analysis of variance and Chi-square/Fisher Exact test.
      RESULTS: The menstrual pain was significantly decreased in both groups after
      three-cycle intervention. Significant changes were observed in VAS (p<0.001) and
      VMSS (p<0.001) in the experimental group. There is a significant (p<0.001)
      reduction in duration of pain in both the groups. Associated symptoms and QOL
      were markedly improved after treatment (p<0.001). CONCLUSIONS: It has been clear
      from the above result that R. emodi is an effective herb in alleviating symptoms
      of primary dysmenorrhoea. It can serve as an alternative treatment without any
      apparent side effects. These results deserve further investigations.

PMID- 25367692
TI  - Stand-up exercise training facilitates muscle recovery from disuse atrophy by
      stimulating myogenic satellite cell proliferation in mice.
AB  - Determining the cellular and molecular recovery processes in inactivity - or
      unloading -induced atrophied muscles should improve rehabilitation strategies. We
      assessed the effects of stand-up exercise (SE) training on the recovery of
      atrophied skeletal muscles in male mice. Mice were trained to stand up and press
      an elevated lever in response to a light-tone cue preceding an electric foot
      shock and then subjected to tail suspension (TS) for 2 weeks to induce disuse
      atrophy in hind limb muscles. After release from TS, mice were divided into SE
      trained (SE cues: 25 times per set, two sets per day) and non-SE-trained groups.
      Seven days after the training, average myofiber cross-sectional area (CSA) of the
      soleus muscle was significantly greater in the SE-trained group than in the non
      SE-trained group (1843 +/- 194 MUm(2) vs. 1315 +/- 153 MUm(2)). Mean soleus
      muscle CSA in the SE trained group was not different from that in the CON group
      subjected to neither TS nor SE training (2005 +/- 196 MUm(2)), indicating that SE
      training caused nearly complete recovery from muscle atrophy. The number of
      myonuclei per myofiber was increased by ~60% in the SE-trained group compared
      with the non-SE-trained and CON groups (0.92 +/- 0.03 vs. 0.57 +/- 0.03 and 0.56
      +/- 0.11, respectively). The number of proliferating myonuclei, identified by 5
      ethynyl-2'-deoxyuridine staining, increased within the first few days of SE
      training. Thus, it is highly likely that myogenic satellite cells proliferated
      rapidly in atrophied muscles in response to SE training and fused with existing
      myofibers to reestablish muscle mass. 

PMID- 25367693
TI  - Nox-4 deletion reduces oxidative stress and injury by PKC-alpha-associated
      mechanisms in diabetic nephropathy.
AB  - Current treatments for diabetic nephropathy (DN) only result in slowing its
      progression, thus highlighting a need to identify novel targets. Increased
      production of reactive oxygen species (ROS) is considered a key downstream
      pathway of end-organ injury with increasing data implicating both mitochondrial
      and cytosolic sources of ROS. The enzyme, NADPH oxidase, generates ROS in the
      kidney and has been implicated in the activation of protein kinase C (PKC), in
      the pathogenesis of DN, but the link between PKC and Nox-derived ROS has not been
      evaluated in detail in vivo. In this study, global deletion of a NADPH-oxidase
      isoform, Nox4, was examined in mice with streptozotocin-induced diabetes
      (C57Bl6/J) in order to evaluate the effects of Nox4 deletion, not only on renal
      structure and function but also on the PKC pathway and downstream events. Nox4
      deletion attenuated diabetes-associated increases in albuminuria,
      glomerulosclerosis, and extracellular matrix accumulation. Lack of Nox4 resulted
      in a decrease in diabetes-induced renal cortical ROS derived from the
      mitochondria and the cytosol, urinary isoprostanes, and PKC activity.
      Immunostaining of renal cortex revealed that major isoforms of PKC, PKC-alpha and
      PKC-beta1, were increased with diabetes and normalized by Nox4 deletion.
      Downregulation of the PKC pathway was observed in tandem with reduced expression
      of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)
      beta1 and restoration of the podocyte slit pore protein nephrin. This study
      suggests that deletion of Nox4 may alleviate renal injury via PKC-dependent
      mechanisms, further strengthening the view that Nox4 is a suitable target for
      renoprotection in diabetes. 

PMID- 25367694
TI  - Caveolin-1 enhances rapid mucosal restitution by activating TRPC1-mediated Ca2+
      signaling.
AB  - Early rapid mucosal restitution occurs as a consequence of epithelial cell
      migration to reseal superficial wounds, a process independent of cell
      proliferation. Our previous studies revealed that the canonical transient
      receptor potential-1 (TRPC1) functions as a store-operated Ca(2+) channel (SOCs)
      in intestinal epithelial cells (IECs) and regulates epithelial restitution after
      wounding, but the exact mechanism underlying TRPC1 activation remains elusive.
      Caveolin-1 (Cav1) is a major component protein that is associated with caveolar
      lipid rafts in the plasma membrane and was recently identified as a regulator of
      store-operated Ca(2+) entry (SOCE). Here, we showed that Cav1 plays an important
      role in the regulation of mucosal restitution by activating TRPC1-mediated Ca(2+)
      signaling. Target deletion of Cav1 delayed gastric mucosal repair after exposure
      to hypertonic NaCl in mice, although it did not affect total levels of TRPC1
      protein. In cultured IECs, Cav1 directly interacted with TRPC1 and formed
      Cav1/TRPC1 complex as measured by immunoprecipitation assays. Cav1 silencing in
      stable TRPC1-transfected cells by transfection with siCav1 reduced SOCE without
      effect on the level of resting [Ca(2+)]cyt. Inhibition of Cav1 expression by
      siCav1 and subsequent decrease in Ca(2+) influx repressed epithelial restitution,
      as indicated by a decrease in cell migration over the wounded area, whereas
      stable ectopic overexpression of Cav1 increased Cav1/TRPC1 complex, induced SOCE,
      and enhanced cell migration after wounding. These results indicate that Cav1
      physically interacts with and activates TRPC1, thus stimulating TRPC1-mediated
      Ca(2+) signaling and rapid mucosal restitution after injury. 

PMID- 25367695
TI  - Enhanced production of IGF-I in the lungs of fibroproliferative ARDS patients.
AB  - Insulin-Like Growth Factor I (IGF-I) has been identified in the lungs of
      individuals with fibrotic lung diseases. In a previous retrospective study, we
      showed enhanced IGF-I immunoreactivity in individuals with fibroproliferative
      acute respiratory distress syndrome (FP-ARDS), but we were unable to determine if
      this correlation was causative. This study was undertaken to prospectively
      investigate whether IGF-I expression correlated with the fibroproliferative
      process and whether IGF-I was induced and made in the lungs. We measured IGF-I
      and procollagen III peptide (PCP-III) in the epithelial lining fluid (ELF) from
      controls, early ALI/ARDS patients and FP-ARDS patients. We also measured IGF-I
      mRNA and immunoreactivity from controls and FP-ARDS patient lung biopsies. We
      determined the level of lung permeability by measuring albumin and urea levels in
      ELF and serum. Our data show that IGF-I is significantly increased in the ELF in
      FP-ARDS patients. A significant correlation between IGF-I and PCP-III in the ELF
      of FP-ARDS patients is found. IGF-I mRNA is elevated in the FP-ARDS lung
      biopsies. Our data suggest that IGF-I found in the lungs of FP-ARDS patients
      results from both increased lung permeability and local production of IGF-I. The
      role of IGF-I in the fibroproliferative process in the lungs has recently been
      confirmed in an animal model of lung fibroproliferation. This study importantly
      suggest that IGF-I protein is made in the lungs of FP-ARDS patients and
      correlates with increased levels of ELF PCP-III, implicating a role for IGF-I in
      the fibroproliferative process in humans. 

PMID- 25367696
TI  - Two new flavonol glycosides from the leaves of Cleome chelidonii L.f.
AB  - From the leaves of Cleome chelidonii L.f., two new flavonol glycosides, named
      cleomesides A (1) and B (2), and four known compounds, quercetin 3-O-beta
      glucopyranosyl(1 -> 2)-alpha-rhamnoside-7-O-alpha-rhamnoside (3), ethyl alpha
      galactopyranoside (4), adenine (5) and glycerol monostearate (6), were isolated.
      The structures of all isolated compounds (1-6) were determined by NMR
      spectroscopy and mass spectrometry. The data of known compounds (3-6) were
      further compared with the reported data for these compounds. 

PMID- 25367697
TI  - Colloidal nanocrystals of lithiated group 14 elements.
AB  - The synthesis of colloidal nanocrystals (NCs) of lithiated group 14 elements
      (Z=Si, Ge, and Sn) is reported, which are Li4.4 Si, Li3.75 Si, Li4.4 Ge, and
      Li4.4 Sn. Lix Z compounds are highly reactive and cannot be synthesized by
      existing methods. The success relied on separating the surface protection from
      the crystal formation and using a unique passivating ligand. Bare Lix Z crystals
      were first produced by milling elemental Li and Z in an argon-filled jar. Then,
      under the assistance of additional milling, hexyllithium was added to passivate
      the freshly generated Lix Z NCs. This ball-milling-assisted surface protection
      method may be generalized to similar systems, such as Nax Z and Kx Z. Moreover,
      Li4.4 Si and Li4.4 Ge NCs were conformally encapsulated in carbon fibers,
      providing great opportunities for studying the potential of using Lix Z to
      mitigate the volume-fluctuation-induced poor cyclability problem confronted by Z
      anodes in lithium-ion batteries. 

PMID- 25367698
TI  - Covalent attachment and growth of nanocrystalline films of photocatalytic TiOF2.
AB  - This manuscript describes a synthesis of nanocrystalline TiOF2 film. The
      nanocrystalline TiOF2 becomes chemically attached to the surface of the glass
      slide. These films are robust and can be recycled as photocatalysts for the
      degradation of organic dyes and solvents. These films also have significant
      antibacterial properties upon irradiation. 

PMID- 25367700
TI  - Fluorescence techniques used to measure interactions between hydroxyapatite
      nanoparticles and epidermal growth factor receptors.
AB  - The potential applications of nanomaterials in therapeutics are immense and to
      fully explore this potential, it is important to understand the interaction of
      nanoparticles with cellular components. To examine the interaction between
      nanoparticles and cell membrane receptors, this report describes the use of
      advanced fluorescence techniques to measure interactions between hydroxyapatite
      (HA) nanoparticles and epidermal growth factor receptors (EGFRs), as a model
      system. FITC-labelled HA nanoparticles and monomeric red fluorescent protein
      (mRFP)-conjugated EGFRs expressed in Chinese hamster ovary cells (CHO-K1) were
      generated and their interaction measured using acceptor photobleaching
      fluorescence resonance energy transfer (AP-FRET) and fluorescence lifetime
      imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET). Results
      confirmed that hydroxyapatite nanoparticles not only interacted with EGFR but
      also attenuated downstream EGFR signalling, possibly by hindering normal
      dimerization of EGFR. Furthermore, the extent of signal attenuation suggested
      correlation with specific surface area of the nanoparticles, whereby greater
      specific surface area resulted in greater downstream signal attenuation. This
      novel demonstration establishes fluorescence techniques as a viable method to
      study nanoparticle interactions with proteins such as cell surface receptors. The
      approach described herein can be extended to study interactions between any
      fluorescently labelled nanoparticle-biomolecule pair. 

PMID- 25367701
TI  - A new method for the preparation of non-terminal alkynes: application to the
      total syntheses of tulearin A and C.
AB  - Lactones are known to react with the reagent generated in situ from CCl4 and PPh3
      in a Wittig-type fashion to give gem-dichloro-olefin derivatives. Such compounds
      are now shown to undergo reductive alkylation on treatment with organolithium
      reagents RLi to furnish acetylene derivatives bearing the substituent R at their
      termini (R=Me, n-, sec-, tert-alkyl, silyl); the reaction can be catalyzed with
      either Cu(acac)2 or Fe(acac)3 /1,2-diaminobenzene. Two alkynol derivatives
      prepared in this way from readily accessible lactone precursors served as the key
      building blocks for the total syntheses of the cytotoxic marine macrolides
      tulearin A (1) and C (2). The assembly of these fragile targets hinged upon ring
      closing alkyne metathesis (RCAM) followed by a formal trans-reduction of the
      resulting cycloalkynes via trans-hydrosilylation/protodesilylation. 

PMID- 25367702
TI  - Controlled growth of few-layer hexagonal boron nitride on copper foils using ion
      beam sputtering deposition.
AB  - Ion beam sputtering deposition (IBSD) is used to synthesize high quality few
      layer hexagonal boron nitride (h-BN) on copper foils. Compared to the
      conventional chemical vapor deposition, the IBSD technique avoids the use of
      unconventional precursors and is much easier to control, which should be very
      useful for the large-scale production of h-BN in the future. 

PMID- 25367703
TI  - Dual optimization method of radiofrequency and quasistatic field simulations for
      reduction of eddy currents generated on 7T radiofrequency coil shielding.
AB  - PURPOSE: To optimize the design of radiofrequency (RF) shielding of transmit
      coils at 7T and reduce eddy currents generated on the RF shielding when imaging
      with rapid gradient waveforms. METHODS: One set of a four-element, 2 * 2 Tic-Tac
      Toe head coil structure was selected and constructed to study eddy currents on
      the RF coil shielding. The generated eddy currents were quantitatively studied in
      the time and frequency domains. The RF characteristics were studied using the
      finite difference time domain method. Five different kinds of RF shielding were
      tested on a 7T MRI scanner with phantoms and in vivo human subjects. RESULTS: The
      eddy current simulation method was verified by the measurement results. Eddy
      currents induced by solid/intact and simple-structured slotted RF shielding
      significantly distorted the gradient fields. Echo-planar images, B1+ maps, and S
      matrix measurements verified that the proposed slot pattern suppressed the eddy
      currents while maintaining the RF characteristics of the transmit coil.
      CONCLUSION: The presented dual-optimization method could be used to design RF
      shielding and reduce the gradient field-induced eddy currents while maintaining
      the RF characteristics of the transmit coil.

PMID- 25367704
TI  - Effects of histamine on ciliary beat frequency of ciliated cells from guinea pigs
      nasal mucosa.
AB  - We aimed to investigate the effect of histamine on ciliary beat frequency (CBF)
      through combining high-speed digital microscopy and patch-clamp technology.
      Ciliated cells were obtained from septum and turbinate of 90-120-day-old healthy
      male guinea pigs. Tight seal was formed by applying negative pressure on the
      glass electrode after the drawing and pushing progress. Then, we enrolled high
      speed digital microscopy to measure CBF before and after treatment with histamine
      of different concentrations ranging from 10(-6) to 10(-1) mol/L in Hank's
      solution and D-Hank's solution as well as after administrating adenosine
      triphosphate. One-way ANOVA, Student's t test or Kruskal-Wallis test was used for
      statistical comparisons. Glass electrode fix up ciliated cell is available at tip
      diameter of 2-5 MUm and negative pressure of 10-20 cmH2O column. The baseline CBF
      in Hank's solution was higher than in D-Hank's solution. Treatment with 10(-6)
      l0(-3) mol/L histamine of concentrations can stimulate a rise of CBF.
      Nevertheless, CBF in all groups decreased to baseline CBF within 20 min.
      Generally, 10(-2) mol/L histamine can stimulate a rise of CBF; meanwhile, the
      high concentration of histamine killed 50% ciliated cell. Histamine at 10(-1)
      mol/L killed all ciliated cells. Ciliary beating activity decreased in Ca(2+)
      free solution. Moreover, adenosine triphosphate could increase CBF effectively
      after the stimulation effect of histamine. We construct an effective technology
      integrating patch-clamp technique with CBF measurements on ciliated cells.
      Extracellular histamine stimulation could increase CBF effectively.

PMID- 25367705
TI  - Non-endemic locoregionally advanced nasopharyngeal carcinoma: long-term outcome
      after induction plus concurrent chemoradiotherapy in everyday clinical practice.
AB  - The aim of this study was to evaluate the long-term outcome in Caucasian
      population of a non-endemic area treated for locoregionally advanced
      nasopharyngeal carcinoma (LA-NPC) with multidrug platinum-based induction plus
      concurrent chemoradiotherapy (IC/CCRT) in everyday clinical practice setting.
      Between May 1990 and July 2007, 75 patients with newly diagnosed histologically
      confirmed LA-NPC were given IC/CCRT. All patients were judged suitable to receive
      conventional fractionated course of radiotherapy to a dose of 70 Gy in 35
      fractions (2 Gy per fraction). The intended chemotherapy regimen consisted in one
      cycle of induction chemotherapy followed by radiotherapy concomitantly with two
      cycles of chemotherapy. Each cycle of chemotherapy included cis-platinum, 100
      mg/m(2), and continuous infusion of 5-fluorouracil, 1,000 mg/m(2)/d for 5 days.
      The median follow-up in survivors was 122 months. The complete response rate
      after CCRT was 90.7%. The main limiting toxicity was grade 3 and 4 pharyngeal
      mucositis (46.7%). Five-year cumulative rate of locoregional control (LRC),
      distant control (DC), overall survival (OS), and event-free survival (EFS) was
      80.1, 82.2, 72.0, and 66.7%, respectively. Ten-year cumulative rate of LRC, DC,
      OS, and EFS was 73.4, 73.8, 57.1, and 55.2%, respectively. At multivariate
      analysis advanced N category and low hemoglobin levels at baseline were found to
      be independent predictors for both worse OS and EFS. In everyday clinical
      practice, treating LA-NPC with cisplatin-based IC/CCRT was relatively safe and
      long-term effective.

PMID- 25367706
TI  - Cochlear implantation in patients with Cogan syndrome: long-term results.
AB  - The objective of this study was to evaluate the long-term outcomes of patients
      with Cogan syndrome (CS) who have undergone cochlear implantation. Subjects
      consisted of 12 cochlear implant users with a typical form of CS. Measures
      included word and sentence recognition scores. The speech recognition performance
      was rated before cochlear implantation and at 1 and 5 years after implantation.
      The speech materials were presented in quiet only condition. The mean 12-month
      post-operative word and sentence recognition scores were 91.4 and 93.1%,
      respectively. Five years after implantation, the group means for word and
      sentence recognition tests were 94 and 96.3%, respectively. No patients in this
      series experienced flap complication or other local or systemic complications.
      This long-term study on 12 subjects with CS over 5 years of cochlear implant use
      reveals that cochlear implantation is safe in the long term and provides
      excellent and stable hearing results.

PMID- 25367708
TI  - Donors contribute more than acceptors to increase the two-photon activity--a case
      study with cyclopenta[b]naphthalene based molecules.
AB  - In the present work, we address the question -"which among the electron donors
      and the electron acceptors contribute more to the two-photon (TP) activity of a
      donor-pi-acceptor type of molecule?" For this purpose we have performed ab initio
      calculations to calculate the TP transition probability (deltaTP) of a recently
      synthesized (Benedetti et al., J. Am. Chem. Soc., 2012, 134(30), 12418-12421)
      cyclopenta[b]naphthalene based chemo-sensor and its derivatives containing
      different electron donor and acceptor groups. Our study revealed that both under
      vacuum and in solvent phases, an increase in electron donor strength (-OMe, -NH2,
      -NMe2) increases the deltaTP value up to five times, whereas, an increase in the
      acceptor group strength (-COCH3, -NO2, -CN) increases it by a factor of two only.
      The highest deltaTP value is obtained for the molecule having the strongest donor
      acceptor pair (-CN, -NMe2) considered in this work. We have also noted that, the
      removal of the cyclopentane ring from the original system increases the deltaTP
      value by ~20% and the replacement of the naphthyl group by the benzene ring
      decreases it by ~70%. All these results are explained by inspecting different TP
      tensor elements and different transition moment vectors involved in a two-state
      model approach. A close scrutiny of different parameters in 2SM clearly reveals
      that upon increasing the strength of either the donor or the acceptor group the
      parameters change in favour of increasing the overall deltaTP values but in the
      case of donors this effect is much larger. 

PMID- 25367707
TI  - Computer-assisted analysis of anatomical relationships of the ethmoidal foramina
      and optic canal along the medial orbital wall.
AB  - Typically, the medial orbital wall contains an anterior ethmoidal foramen (EF)
      and a posterior EF, but may also have multiple EFs transmitting the arteries and
      nerves between the orbit and the anterior cranial fossa. The aim of this study is
      to determine a patient-friendly landmark of the medial orbital wall and to
      specify a precise location of the ethmoidal foramens (EF) in order to standardize
      certain anatomical marks as safe ethmoidal arteries. Orientation points on the
      anterior ethmoidal foramen (AEF), posterior ethmoidal foramen (PEF) and middle
      ethmoidal foramen (MEF) were investigated in 262 orbits. Using a software
      program, distances between each foramen and the midpoint of the anterior lacrimal
      crest (ALC), the optic canal (OC), and some important angles were measured. The
      EFs were identified as single in 0.8%, double in 73.7%, triple 24,4% and
      quadruple in 1.1% specimens. The mean distances between ALC and AEF, ALC and PEF
      and ALC and MEF were 27.7, 10.6, and 12.95 mm, respectively. The distances from
      ALC-AEF, AEF-PEF, and PEF-OC were 27.7 +/- 2.8, 10.6 +/- 3.3, 5.4 +/- 1 mm. The
      angles from the plane of the EF to the medial border of the OC were calculated as
      13.2 degrees  and 153 degrees , respectively. The angle from the AEF to the
      medial border of the OC was based on the plane between the ALC and AEF was 132
      degrees . The occurrence of multiple EF with an incidence of 25% narrows the
      borders of the safe region in the medial orbital wall. Safe distance of the ALC
      EF was measured as 22.1 mm on medial wall. The line of the location of the EF was
      calculated 16.2 mm. In this study, it was possible to investigate the variability
      of the orbital orifice of the EF and the feasibility of the EA, to observe
      various angles of the orbital wall bones and to calculate the lengths of some
      parameters with the help of certain software.

PMID- 25367709
TI  - Objective assessment of vitiligo with a computerised digital imaging analysis
      system.
AB  - An objective tool to quantify treatment response in vitiligo is currently
      lacking. This study aimed to objectively evaluate the treatment response in
      vitiligo by using a computerised digital imaging analysis system (C-DIAS) and to
      compare it with the physician's global assessment (PGA). Tacrolimus ointment 0.1%
      (Protopic; Astellas Pharma Tech,Toyama, Japan) was applied twice daily on
      selected lesions which were photographed every 6 weeks for 24 weeks. The primary
      efficacy end-point was the mean percentage of repigmentation (MPR), as assessed
      by the digital method (MPR-C-DIAS) or by the PGA. The response was categorised
      into none (0%), mild (1-25%), moderate (26-50%), good (51-75%) and excellent (76
      100%). MPR-C-DIAS: Out of 56 patients, 44 (79%) responded. Overall, the response
      was mild in 22 (39%), moderate in 21(40%) and good in one (2%) patient(s). A
      total of 39 (70%) patients responded as measured by PGA. The repigmentation was
      mild in 27(48%), moderate in 10 (18%) and good to excellent in two (4%) patients.
      The kappa test of consistency was 0.17 (P = 0.053), which shows poor agreement
      between the two assessment methods, although this is not statistically
      significant. The C-DIAS can be used to perform an objective analysis of
      repigmentation or depigmentation in vitiligo skin lesions in response to
      treatment.

PMID- 25367710
TI  - iTRAQ protein profile differential analysis between somatic globular and
      cotyledonary embryos reveals stress, hormone, and respiration involved in
      increasing plantlet regeneration of Gossypium hirsutum L.
AB  - Somatic embryo development (SED) in upland cotton shows low frequencies of embryo
      maturation and plantlet regeneration. Progress in increasing the regeneration
      rate has been limited. Here a global analysis of proteome dynamics between
      globular and cotyledonary embryos was performed using isobaric tags for relative
      and absolute quantitation to explore mechanisms underlying SED. Of 6318 proteins
      identified by a mass spectrometric analysis, 102 proteins were significantly up
      regulated and 107 were significantly down-regulated in cotyledonary embryos. The
      differentially expressed proteins were classified into seven functional
      categories: stress responses, hormone synthesis and signal transduction,
      carbohydrate and energy metabolism, protein metabolism, cell wall metabolism,
      cell transport, and lipid metabolism. KEGG (Kyoto Encyclopedia of Genes and
      Genomes) analysis showed that stress response, hormone homeostasis, and
      respiration and photosynthesis were involved in SED. Quantitative real-time PCR
      analysis confirmed the authenticity and accuracy of the proteomic analysis.
      Treatment of exogenous hormones showed that abscisic acid and jasmonic acid
      facilitate SED, whereas gibberellic acid inhibits SED and increases abnormal
      embryo frequency. Thus, global analysis of proteome dynamics reveals that stress
      response, hormone homeostasis, and respiration and photosynthesis determined
      cotton SED. The findings of this research improve the understanding of molecular
      processes, especially environmental stress response, involved in cotton SED. 

PMID- 25367711
TI  - Effect of light-emitting diode (y 627 nm and 945 nm y) treatment on first
      intention healing: immunohistochemical analysis.
AB  - Collagen I is not only responsible for maintaining the integrity of most tissues
      due to its mechanical properties, but also for its active participation in the
      functionality of tissues because of its interaction with cells present in the
      extracellular matrix. The synthesis of collagen begins with tissue injury and
      remains until the end of the healing process. The use of non-coherent light for
      healing processes is still understudied. This procedure stands out as a
      biostimulation method for tissue repair, which increases local circulation, cell
      proliferation, and collagen synthesis. This study sought to quantify collagen I
      in the healing process after the treatment of wounds with the light-emitting
      diode (LED) treatment. The histologic analysis with tissue samples stained with
      picrosirius red showed a statistical difference between the positive controls,
      LED 627 and LED 945 nm groups; the group treated with LED 627 nm showed a
      predominance of mature collagen. The immunohistochemical analysis showed a
      statistically significant high concentration of collagen I in the LED 945 nm
      group. The irradiation of wounds with the higher wavelength (945 nm) used in the
      study produced the best activity of collagen I formation in experimental model.

PMID- 25367712
TI  - Comparison of acute elastic recoil between the SAPIEN-XT and SAPIEN valves in
      transfemoral-transcatheter aortic valve replacement.
AB  - BACKGROUND: The SAPIEN-XT is a newer generation balloon-expandable valve created
      of cobalt chromium frame, as opposed to the stainless steel frame used in the
      older generation SAPIEN valve. We sought to determine if there was difference in
      acute recoil between the two valves. METHODS: All patients who underwent
      transfemoral-transcatheter aortic valve replacement using the SAPIEN-XT valve at
      the Cleveland Clinic were included. Recoil was measured using biplane cine
      angiographic image analysis of valve deployment. Acute recoil was defined as
      [(valve diameter at maximal balloon inflation) - (valve diameter after
      deflation)]/valve diameter at maximal balloon inflation (reported as percentage).
      Patients undergoing SAPIEN valve implantation were used as the comparison group.
      RESULTS: Among the 23 mm valves, the mean (standard deviation-SD) acute recoil
      was 2.77% (1.14) for the SAPIEN valve as compared to 3.75% (1.52) for the SAPIEN
      XT valve (P = 0.04). Among the 26 mm valves, the mean (SD) acute recoil was 2.85%
      (1.4) for the SAPIEN valve as compared to 4.32% (1.63) for the SAPIEN XT valve (P
      = 0.01). Multivariable linear regression analysis demonstrated significantly
      greater adjusted recoil in the SAPIEN XT valves as compared to the SAPIEN valves
      by 1.43% [(95% CI: 0.69-2.17), P < 0.001]. However, the residual peak gradient
      was less for SAPIEN XT compared to SAPIEN valves [18.86 mm Hg versus 23.53 mm Hg
      (P = 0.01)]. Additionally, no difference in paravalvular leak was noted between
      the two valve types (P = 0.78). CONCLUSIONS: The SAPIEN XT valves had
      significantly greater acute recoil after deployment compared to the SAPIEN
      valves. Implications of this difference in acute recoil on valve performance need
      to be investigated in future studies.

PMID- 25367713
TI  - Evaluating drug-free remission with abatacept in early rheumatoid arthritis:
      results from the phase 3b, multicentre, randomised, active-controlled AVERT study
      of 24 months, with a 12-month, double-blind treatment period.
AB  - OBJECTIVES: To evaluate clinical remission with subcutaneous abatacept plus
      methotrexate (MTX) and abatacept monotherapy at 12 months in patients with early
      rheumatoid arthritis (RA), and maintenance of remission following the rapid
      withdrawal of all RA treatment. METHODS: In the Assessing Very Early Rheumatoid
      arthritis Treatment phase 3b trial, patients with early active RA were randomised
      to double-blind, weekly, subcutaneous abatacept 125 mg plus MTX, abatacept 125 mg
      monotherapy, or MTX for 12 months. Patients with low disease activity (Disease
      Activity Score (DAS)28 (C reactive protein (CRP)) <3.2) at month 12 entered a 12
      month period of withdrawal of all RA therapy. The coprimary endpoints were the
      proportion of patients with DAS28 (CRP) <2.6 at month 12 and both months 12 and
      18, for abatacept plus MTX versus MTX. RESULTS: Patients had <2 years of RA
      symptoms, DAS28 (CRP) >=3.2, anticitrullinated peptide-2 antibody positivity and
      95.2% were rheumatoid factor positive. For abatacept plus MTX versus MTX, DAS28
      (CRP) <2.6 was achieved in 60.9% versus 45.2% (p=0.010) at 12 months, and
      following treatment withdrawal, in 14.8% versus 7.8% (p=0.045) at both 12 and 18
      months. DAS28 (CRP) <2.6 was achieved for abatacept monotherapy in 42.5% (month
      12) and 12.4% (both months 12 and 18). Both abatacept arms had a safety profile
      comparable with MTX alone. CONCLUSIONS: Abatacept plus MTX demonstrated robust
      efficacy compared with MTX alone in early RA, with a good safety profile. The
      achievement of sustained remission following withdrawal of all RA therapy
      suggests an effect of abatacept's mechanism on autoimmune processes. TRIAL
      REGISTRATION NUMBER: NCT01142726.

PMID- 25367715
TI  - Detection of QTc effects in small studies--implications for replacing the
      thorough QT study.
AB  - BACKGROUND: ECG assessment with exposure response analysis applied to data from
      First-in-Man studies has been proposed to replace the thorough QT study for the
      detection of small QT effects. METHODS: Data from five thorough QT studies, three
      with moxifloxacin, one study with a drug with a large QTc effect (~25 ms) and one
      with ketoconazole with a smaller QT effect (~8 ms) were used. By subsampling,
      studies with 6-18 subjects on drug and six on placebo were simulated 1000 times
      per sample size to assess whether small QTc effects using ICH E14 criteria could
      be excluded and the impact of sample size on the estimate and variability of the
      slope of the concentration/QTc relation. RESULTS: With a sample size of nine or
      more on drug and six on placebo, the fraction of "false negative studies" was at
      or below 5% with data from the studies with moxifloxacin and from the drug with a
      large QTc effect. With the same sample size and no underlying QTc effect
      (placebo), the fraction of studies in which an effect above 10 ms could be
      excluded was above 85%. A treatment effect in the linear concentration-effect
      model resulted in a lower proportion of "false negatives." Sample size had little
      influence on the average slope estimate of the concentration/QTc relationship.
      CONCLUSIONS: For drugs with a QTc effect of around 12-14 ms, exposure response
      analysis applied to First-in-Man studies with careful ECG assessment can be used
      to replace the through QT study.

PMID- 25367714
TI  - Is axillary lymph node clearance required in node-positive breast cancer?
AB  - Although the majority of patients with breast cancer have clinically negative
      axillary nodes at preoperative assessment, around 15-20% of these women will have
      metastatic disease within the lymph nodes at operative sentinel node biopsy, and
      additional selective treatment to the axilla might be required. Local treatment
      to the axilla can include axillary node clearance or axillary radiotherapy. The
      recent results of the American College of Surgeons Oncology Group Z0011 trial
      suggested that some women would be safe from recurrence without further axillary
      treatment if they have less than three involved sentinel nodes, with no
      extracapsular spread. We review the evidence base for management of the axilla
      after detection of a positive sentinel node, discuss the evidence for why
      micrometastatic disease requires systemic but not axillary therapy, and present
      data suggesting that axillary irradiation for macrometastases gives equivalent
      control to axillary node clearance, but causes less morbidity such as
      lymphoedema. Ongoing trials will confirm whether any further therapy can be
      omitted for all patients with low volume, sentinel-node macrometastases. 

PMID- 25367716
TI  - Dulaglutide: first global approval.
AB  - Dulaglutide (TrulicityTM) is a long-acting, glucagon-like peptide-1 (GLP-1)
      receptor agonist that has been developed by Eli Lilly and Company for the
      treatment of type 2 diabetes mellitus. It consists of a dipeptidyl peptidase-IV
      protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a
      small peptide linker. The subcutaneous formulation is approved for use in type 2
      diabetes in the US, has been recommended for approval in the EU in this
      indication, and is under regulatory review in other countries. This article
      summarizes the milestones in the development of subcutaneous dulaglutide leading
      to this first approval for type 2 diabetes. 

PMID- 25367718
TI  - Allogeneic head and body reconstruction: mouse model.
AB  - AIMS: There is still no effective way to save a surviving healthy mind when there
      is critical organ failure in the body. The next frontier in CTA is allo-head and
      body reconstruction (AHBR), and just as animal models were key in the development
      of CTA, they will be crucial in establishing the procedures of AHBR for clinical
      translation. METHODS AND RESULTS: Our approach, pioneered in mice, involves
      retaining the donor brain stem and transplanting the recipient head. Our
      preliminary data in mice support that this allows for retention of breathing and
      circulatory function. Critical aspects of the current protocol include avoiding
      cerebral ischemia through cross-circulation (donor to recipient) and retaining
      the donor brain stem. Successful clinical translation of AHBR will become a
      milestone of medical history and potentially could save millions of people.
      CONCLUSIONS: This experimental study has confirmed a method to avoid cerebral
      ischemia during the surgery and solved an important part of the problem of how to
      accomplish long-term survival after transplantation and preservation of the donor
      brain stem.

PMID- 25367717
TI  - Liraglutide: a review of its use in adult patients with type 2 diabetes mellitus.
AB  - Subcutaneous liraglutide (Victoza((r))), a glucagon-like peptide 1 receptor
      agonist, is approved for the treatment of adult patients with type 2 diabetes
      mellitus. Once-daily liraglutide, as monotherapy or add-on therapy to other
      antidiabetic agents (including basal insulin), was an effective and generally
      well tolerated treatment in adult patients with type 2 diabetes in several well
      designed phase III trials and in the real world clinical practice setting. In
      addition to improving glycaemic control, liraglutide had beneficial effects on
      bodyweight, systolic blood pressure and surrogate measures of beta-cell function
      in clinical trials, with these benefits maintained during long-term treatment
      (<=2 years). Liraglutide has a convenient once-daily administration regimen, a
      low potential for drug-drug interactions and low propensity to cause
      hypoglycaemia. Thus, liraglutide continues to be a useful option for the
      management of type 2 diabetes. This article reviews the therapeutic use of
      liraglutide in adult patients with type 2 diabetes and summarizes its
      pharmacological properties.

PMID- 25367719
TI  - Contributions of purinergic P2X3 receptors within the midbrain periaqueductal
      gray to diabetes-induced neuropathic pain.
AB  - Hyperalgesia and allodynia are commonly observed in patients with diabetic
      neuropathy. The mechanisms responsible for neuropathic pain are not well
      understood. Thus, in this study, we examined the role played by purinergic P2X3
      receptors of the midbrain periaqueductal gray (PAG) in modulating diabetes
      induced neuropathic pain because this brain region is an important component of
      the descending inhibitory system to control central pain transmission. Our
      results showed that mechanical withdrawal thresholds were significantly increased
      by stimulation of P2X3 receptors in the dorsolateral PAG of rats (n = 12, P <
      0.05 vs. vehicle control) using alpha,beta-methylene-ATP (alpha,beta-meATP, a
      P2X3 receptor agonist). In addition, diabetes was induced by an intraperitoneal
      injection of streptozotocin (STZ) in rats, and mechanical allodynia was observed
      3 weeks after STZ administration. Notably, the excitatory effects of P2X3
      stimulation on mechanical withdrawal thresholds were significantly blunted in STZ
      induced diabetic rats (n = 12, P < 0.05 vs. control animals) as compared with
      control rats (n = 12). Furthermore, the protein expression of P2X3 receptors in
      the plasma membrane of the dorsolateral PAG of STZ-treated rats was significantly
      decreased (n = 10, P < 0.05 vs. control animals) compared to that in control rats
      (n = 8), whereas the total expression of P2X3 receptors was not significantly
      altered. Overall, data of our current study suggest that a decrease in the
      membrane expression of P2X3 receptors in the PAG of diabetic rats is likely to
      impair the descending inhibitory system in modulating pain transmission and
      thereby contributes to the development of mechanical allodynia in diabetes.

PMID- 25367720
TI  - -NMDA R/+VDR pharmacological phenotype as a novel therapeutic target in relieving
      motor-cognitive impairments in Parkinsonism.
AB  - BACKGROUND: Parkinsonism describes Parkinson's disease and other associated
      degenerative changes in the brain resulting in movement disorders. The motor
      cortex, extrapyramidal tracts and nigrostriatal tract are brain regions forming
      part of the motor neural system and are primary targets for drug or chemotoxins
      induced Parkinsonism. The cause of Parkinsonism has been described as wide and
      elusive, however, environmental toxins and drugs accounts for large percentage of
      spontaneous cases in humans. A common mechanism in the cause and progression of
      drug/chemotoxin induced Parkinsonism involves calcium signalling in; oxidative
      stress, autophagy, cytoskeletal instability and excitotoxicity . AIM: This study
      sets to investigate the effect of targeting calcium controlling receptors,
      specifically activation of Vitamin D3 receptor (VDR) and inhibition of N-Methyl-D
      Aspartate Receptor (NMDAR) in the motor cortex of mice model of drug induced
      Parkinsonism. Also we demonstrated how these interventions improved neural
      activity, cytoskeleton, glia/neuron count and motor-cognitive functions in vivo.
      METHODS: Adult mice were separated into six groups of n = 5 animals each. Body
      weight (5 mg/kg) of haloperidol was administered intraperitoneally for 7 days to
      block dopaminergic D2 receptors and induce degeneration in the motor cortex
      following which an intervention of VDR agonist (VDRA), and (or) NMDAR inhibitor
      was administered for 7 days. A set of control animals received normal saline
      while a separate group of control animals received the combined intervention of
      VDRA and NMDAR inhibitor without prior treatment with haloperidol. Behavioral
      tests for motor and cognitive functions were carried out at the end of the
      treatment and intervention periods. Subsequently, neural activity in the motor
      cortex was recorded in vivo using unilateral wire electrodes. We also employed
      immunohistochemistry to demonstrate neuron, glia, neurofilament and proliferation
      in the motor cortex after haloperidol treatment and the intervention.
      RESULT/DISCUSSION: We observed a decline in motor function and memory index in
      the haloperidol treatment group when compared with the control. Similarly, there
      was a decline in neural activity in the motor cortex (a reduced depolarization
      peak frequency). General cell loss (neuron and glia) and depletion of
      neurofilament were characteristic anatomical changes seen in the motor cortex of
      this group. However, Vitamin D3 intervention facilitated an improvement in motor
      cognitive function, neural activity, glia/neuron survival and neurofilament
      expression. NMDAR inhibition and the combined intervention improved motor
      cognitive functions but not as significant as values observed in VDRA
      intervention. Interestingly, animals treated with the combined intervention
      without prior haloperidol treatment showed a decline in motor function and neural
      activity. CONCLUSION: Our findings suggest that calcium mediated toxicity is
      primary to the cause and progression of Parkinsonism and targeting receptors that
      primarily modulates calcium reduces the morphological and behavioral deficits in
      drug induced Parkinsonism. VDR activation was more effective than NMDAR
      inhibition and a combined intervention. We conclude that targeting VDR is key for
      controlling calcium toxicity in drug/chemotoxin induced Parkinsonism.

PMID- 25367723
TI  - Heparins for preventing venous thromboembolism in general medical wards: evidence
      and guidelines.

PMID- 25367721
TI  - Implementation of newly adopted technology in acute care settings: a qualitative
      analysis of clinical staff.
AB  - Technologies are not always successfully implemented into practice. This study
      elicited experiences of acute care providers with the introduction of technology
      and identified barriers and facilitators in the implementation process. A
      qualitative study using one-on-one interviews among a purposeful sample of 19
      physicians and nurses within 10 emergency departments and intensive care units
      was performed. Grounded theory, iterative data analysis and the constant
      comparative method were used to inductively generate ideas and build theories.
      Five major categories emerged: decision-making factors, the impact on practice,
      technology's perceived value, facilitators and barriers to implementation.
      Barriers included negative experiences, age, infrequent use and access
      difficulties. A positive outlook, sufficient training, support staff and user
      friendliness were facilitators. This study describes strategies implicated in the
      successful implementation of newly adopted technology in acute care settings.
      Improved implementation methods and evaluation of implementation processes are
      necessary for successful adoption of new technology.

PMID- 25367722
TI  - Dried blood spot in the genotyping, quantification and storage of HCV RNA: a
      systematic literature review.
AB  - The entry of new all-oral direct acting antiviral therapy for hepatitis C
      provides an opportunity to scale up HCV care in low- and middle-income countries.
      In HIV, use of dried blood spots (DBS) has facilitated the diagnosis and
      management of HIV in resource-poor settings. DBS may be used in a similar way to
      facilitate diagnosis and management of HCV. Here, we present a systematic review
      of the literature of DBS for HCV RNA detection and genotyping. Using an a priori
      review protocol, three databases were searched for studies published up to August
      2013 that reported the use of dried blood and serum spots in genotyping,
      detection and measurement of HCV RNA, as well as the rate of degradation of HCV
      RNA when stored in DBS at room temperature. Nine papers were eligible for
      inclusion; eight studied DBS and one dried serum. Two studies measured
      concordance between genotype and subtype determined by DBS and whole plasma and
      both found 100% concordance. Four studies measured endpoint detection limits of
      HCV RNA-positive samples by DBS and found positive predictive values of 100% down
      to 250, 334, 2500 and 24160 IU/mL. Two studies found deterioration of HCV RNA in
      DBS samples stored at room temperature, while two others failed to detect such
      deterioration. These results support the potential use of DBS for genotyping and
      HCV RNA detection. Studies of the use of DBS for HCV RNA viral load measurement
      and of the rate of degradation of HCV RNA when stored in DBS at ambient
      temperatures remain inconclusive.

PMID- 25367724
TI  - Heparin-based treatment to prevent symptomatic deep venous thrombosis, pulmonary
      embolism or death in general medical inpatients is not supported by best
      evidence.
AB  - Prevention of venous thromboembolism (VTE) in medical patients is controversial.
      In contrast to surgical patients, the evidence supporting the use of heparin
      based treatment for prevention of VTE (HVTEp) may not justify current guidelines.
      This study aims to determine whether current clinical guidelines for HVTEp are
      appropriate for medical patients. We searched medical databases for original
      randomised placebo-controlled studies of HVTEp in medical patients, excluding
      those with stroke and in intensive care. From 401 potentially relevant studies,
      we selected eight, which included over 16 000 patients. HVTEp decreased the
      incidence of all deep venous thromboses (DVT): 4.3% in the placebo group versus
      2.3% in the treatment group, P = 0.002, number needed to treat, 50. However, this
      treatment effect was not seen for symptomatic DVT: 1.2% versus 0.9%, P = 0.18,
      odds ratio (OR) 0.72 (0.45-1.16). Similarly, HVTEp did not decrease the incidence
      of pulmonary embolism (PE): 0.54% versus 0.27%, P = 0.3, OR 0.57 (0.21-1.53), or
      fatal PE: 0.1% versus 0.0%, P = 0.3, OR 0.2 (0.01-4.11). Furthermore, HVTEp did
      not decrease total mortality: 5.63% versus 5.39%, P = 0.92, OR 0.96 (0.78-1.18).
      The use of HVTEp in hospitalised general medical patients does not result in a
      significant reduction in symptomatic DVT, PE, fatal PE or total mortality. The
      best evidence does not support the recommendations of the current clinical
      guidelines. 

PMID- 25367725
TI  - Dementia in older people: an update.
AB  - Dementia is a common condition of the elderly characterised by multiple cognitive
      deficits resulting in a decline from previous level of function. In the older
      person, multiple pathologies contribute, including changes commonly seen in
      Alzheimer disease, dementia with Lewy bodies in addition to vascular changes.
      Comorbid factors, such as depression, delirium and polypharmacy can contribute to
      cognitive decline. Novel biomarkers and neuroimaging techniques may assist in the
      near future to improve accuracy of diagnosis. To date, pharmacological therapies
      have been largely unsuccessful and provide symptomatic relief only. The timely
      diagnosis of dementia can facilitate important discussions regarding personal and
      financial planning and introduce education and supports to the person with
      dementia and their carers. The person with dementia commonly experiences
      behavioural and psychological symptoms of dementia that may cause much distress,
      including to families and carers. Clinical guidelines indicate non
      pharmacological approaches as first line measures, including attention to pain,
      nutrition and the environment. Dementia is recognised as a National Health
      Priority in Australia, and efforts to target risk factors as preventative
      measures to delay onset of dementia require further urgent consideration. 

PMID- 25367726
TI  - Transition from hospital to primary care: an audit of discharge summary -
      medication changes and follow-up expectations.
AB  - BACKGROUND: The clinical discharge summary remains a critical, but often poorly
      implemented tool in communication with primary care. An area of concern is the
      documentation of medication lists and appropriate follow up of medication
      changes. AIMS: To assesses the accuracy of documentation of medication changes
      and expectations with regard to follow up from an acute assessment unit (AAU) of
      a tertiary metropolitan hospital. METHODS: All patients who were admitted and
      discharged directly from the unit during the month of June 2013 were audited. For
      all admissions, discharge summaries were audited for medication errors and for
      the appropriate documentation of indications and follow up for prescribed
      medications. All medications prescribed on discharge were collated using the
      World Health Organization Anatomical, Therapeutic and Chemical (ATC)
      classification. RESULTS: In total, 219 admissions were analysed. There were 204
      out of 219 (93.1%) discharge summaries that had an accurate medication list. Of
      219 (74%) patients, 163 had at least one change to their medications during
      admission. Of 163 discharge summaries, 82 (50%) contained information regarding
      their indication and outpatient management. The most commonly prescribed classes
      along with the rates of indication and follow up documentation were anti
      infectives (62%), gastrointestinal (51%), cardiovascular (50%) and central
      nervous system (44%). CONCLUSION: Although there were fewer documentation errors
      in discharge summaries than previously described in the literature, concerns
      regarding the documentation of medication indication and follow up remain.

PMID- 25367727
TI  - Antithrombotic use following transient ischaemic attack or ischaemic stroke among
      older Australians with atrial fibrillation.
AB  - Hospital audits may underestimate anticoagulant use among acute ischaemic stroke
      patients with atrial fibrillation (AF), as treatment may commence after
      discharge. To account for this, antithrombotic use in the 4 months after
      hospitalisation for transient ischaemic attack or ischaemic stroke among AF
      patients was assessed using claims data. Results suggest that treatment may be
      commenced soon after discharge and should be considered when assessing prevalence
      of use. 

PMID- 25367728
TI  - Maturity-onset diabetes of the young type 5 in a family with diabetes and mild
      kidney disease diagnosed by whole exome sequencing.
AB  - Exome sequencing is being increasingly used to identify disease-associated gene
      mutations. We used whole exome sequencing to determine the genetic basis of a
      syndrome of diabetes and renal disease affecting a mother and her son. We
      identified a mutation in the hepatocyte nuclear factor 1-b (HNF1B) gene that
      encoded a methionine to valine amino acid change (M160V) in the HNF1B protein.
      This leads us to the previously unappreciated diagnosis of maturity-onset
      diabetes of the young type 5 and provided a basis for genetic counselling of
      other family members. 

PMID- 25367729
TI  - Why closing the Aboriginal health gap is so elusive.
AB  - A wide gap persists between the health of Aboriginal and non-Aboriginal
      Australians despite a recent Federal government commitment to close the gap by
      2030. The complex underlying factors include socioeconomic and environmental
      disadvantage, inadequate education, underemployment, racial prejudice, high-risk
      health-related behaviours and limited access to clinical services and health
      promotion programmes. Over recent decades some aspects of Aboriginal health have
      deteriorated badly, largely from a surge in chronic 'lifestyle' diseases like
      diabetes, cardiovascular and kidney disorders plus the effects of tobacco
      smoking, alcohol and drug abuse and high rates of violence and trauma. To correct
      these inequities will require improving many social and environmental factors.
      These include education, living conditions, vocational training, employment,
      closer cooperation between government and non-government agencies, access to
      affordable and nutritious fresh food, with better access to high-quality medical
      treatment, health promotion and disease prevention programmes. Indigenous people
      must be encouraged to become more involved in activities to improve their health
      and have more responsibility for the decision-making processes this will entail.
      Governments must support these changes to help close the Aboriginal health gap. 

PMID- 25367730
TI  - Uhthoff phenomenon in osmotic demyelination syndrome.

PMID- 25367731
TI  - Recalcitrant paraneoplastic pemphigus associated with follicular dendritic cell
      sarcoma: response to prolonged rituximab and ciclosporin therapy.

PMID- 25367732
TI  - Kikuchi-Fujimoto disease: an esoteric cause of fever and lymphadenopathy in the
      young patient.

PMID- 25367733
TI  - It's time to move beyond trying to predict mortality using severity assessment
      tools in community-acquired pneumonia.

PMID- 25367734
TI  - Author reply: To PMID 24946819.

PMID- 25367735
TI  - Method of choice for imaging metastatic calcification, due to hypercalcaemia from
      any cause, is a radionuclide bone scan.

PMID- 25367736
TI  - Sensory data fusion of pressure mattress and wireless inertial magnetic
      measurement units.
AB  - Head movement of infants is an important parameter for analysing infant motor
      patterns. Despite its importance, this field has received little sensory-based
      research in the past years. Therefore, we present a sensory-supported data fusion
      model for head movement analysis of infants in supine position. The sensory
      system comprises a pressure mattress and two wireless inertial magnetic
      measurement units, rendering precise, objective and non-intrusive information on
      pressure distribution and 3D trunk orientation, respectively. Algorithms first
      perform pressure data pre-processing and calculate image moments to acquire 2D
      trunk orientation. Afterwards, unscented Kalman filter is used for sensory data
      fusion. After additional data processing, head and trunk coordinates are
      calculated along with head displacement distance. The sensory system was tested
      on experimental measurements, performed in eight normally developing infants aged
      from 1 to 5 months. Results of several algorithm combinations were compared to
      referential video recordings in terms of head lifts. Combination of algorithms,
      incorporating head tracking and sensory data fusion provides completely accurate
      results in comparison to normative data. Statistical data analysis and
      referential optoelectronic measurements were performed to evaluate accuracy of
      the sensory fusion model. Suitability of the proposed sensory system for head
      movement analysis of infants in supine position was verified.

PMID- 25367737
TI  - The influence of alignment-free sequence representations on the semi-supervised
      classification of class C G protein-coupled receptors: semi-supervised
      classification of class C GPCRs.
AB  - G protein-coupled receptors (GPCRs) are integral cell membrane proteins of
      relevance for pharmacology. The tertiary structure of the transmembrane domain, a
      gate to the study of protein functionality, is unknown for almost all members of
      class C GPCRs, which are the target of the current study. As a result, their
      investigation must often rely on alignments of their amino acid sequences.
      Sequence alignment entails the risk of missing relevant information. Various
      approaches have attempted to circumvent this risk through alignment-free
      transformations of the sequences on the basis of different amino acid
      physicochemical properties. In this paper, we use several of these alignment-free
      methods, as well as a basic amino acid composition representation, to transform
      the available sequences. Novel semi-supervised statistical machine learning
      methods are then used to discriminate the different class C GPCRs types from the
      transformed data. This approach is relevant due to the existence of orphan
      proteins to which type labels should be assigned in a process of deorphanization
      or reverse pharmacology. The reported experiments show that the proposed
      techniques provide accurate classification even in settings of extreme class
      label scarcity and that fair accuracy can be achieved even with very simple
      transformation strategies that ignore the sequence ordering.

PMID- 25367738
TI  - Automatic detection of motion blur in intravital video microscopy image sequences
      via directional statistics of log-Gabor energy maps.
AB  - Intravital microscopy is an important experimental tool for the study of cellular
      and molecular mechanisms of the leukocyte-endothelial interactions in the
      microcirculation of various tissues and in different inflammatory conditions of
      in vivo specimens. However, due to the limited control over the conditions of the
      image acquisition, motion blur and artifacts, resulting mainly from the heartbeat
      and respiratory movements of the in vivo specimen, will very often be present.
      This problem can significantly undermine the results of either visual or
      computerized analysis of the acquired video images. Since only a fraction of the
      total number of images are usually corrupted by severe motion blur, it is
      necessary to have a procedure to automatically identify such images in the video
      for either further restoration or removal. This paper proposes a new technique
      for the detection of motion blur in intravital video microscopy based on
      directional statistics of local energy maps computed using a bank of 2D log-Gabor
      filters. Quantitative assessment using both artificially corrupted images and
      real microscopy data were conducted to test the effectiveness of the proposed
      method. Results showed an area under the receiver operating characteristic curve
      (AUC) of 0.95 (AUC = 0.95; 95 % CI 0.93-0.97) when tested on 329 video images
      visually ranked by four observers.

PMID- 25367739
TI  - A micro-sized bio-solar cell for self-sustaining power generation.
AB  - Self-sustainable energy sources are essential for a wide array of wireless
      applications deployed in remote field locations. Due to their self-assembling and
      self-repairing properties, "biological solar (bio-solar) cells" are recently
      gaining attention for those applications. The bio-solar cell can continuously
      generate electricity from microbial photosynthetic and respiratory activities
      under day-night cycles. Despite the vast potential and promise of bio-solar
      cells, they, however, have not yet successfully been translated into commercial
      applications, as they possess persistent performance limitations and scale-up
      bottlenecks. Here, we report an entirely self-sustainable and scalable microliter
      sized bio-solar cell with significant power enhancement by maximizing solar
      energy capture, bacterial attachment, and air bubble volume in well-controlled
      microchambers. The bio-solar cell has a ~300 MUL single chamber defined by laser
      machined poly(methyl methacrylate) (PMMA) substrates and it uses an air cathode
      to allow freely available oxygen to act as an electron acceptor. We generated a
      maximum power density of 0.9 mW m(-2) through photosynthetic reactions of
      cyanobacteria, Synechocystis sp. PCC 6803, which is the highest power density
      among all micro-sized bio-solar cells. 

PMID- 25367740
TI  - Factors associated with support for smoke-free policies among government workers
      in Six Chinese cities: a cross-sectional study.
AB  - BACKGROUND: A certain level of public support for smoke-free environments is a
      prerequisite for adoption and enforcement of policies and can be used as an
      indicator of readiness for legislative action. This study assessed support for
      comprehensive smoke-free policies in a range of settings such as hotels and
      colleges among government workers in China and identified factors associated with
      support for smoke-free policies. Understanding the extent to which government
      workers, a large segment of the working population in China, report a smoke-free
      workplace and support for smoke-free policies may be important indicators of
      readiness for strengthened policies given their role in formulating, implementing
      and enforcing regulations. METHODS: Data were from an evaluation of the Tobacco
      Free Cities initiative of Emory University's Global Health Institute-China
      Tobacco Control Partnership. Self-administered surveys were completed by 6,646
      workers in 160 government agencies in six Chinese cities. Multivariate logistic
      regression was used to identify factors associated with support for smoke-free
      worksites, bars, hotels, and colleges. RESULTS: Over half (54.6%) of participants
      were male. A large percentage of the male workers smoked (45.9%,) whereas very
      few women did (1.9%). Fewer than 50% of government workers reported smoke-free
      policies at work, with 19.0% reporting that smoking is allowed anywhere. Support
      for smoke-free policies was generally very high, with the lowest levels of
      support for smoke-free bars (79.0%) and hotels (82.3%), higher levels of support
      for restaurants (90.0%) and worksites (93.0%), and above 95% support for
      hospitals, schools, colleges, public transportation and religious settings.
      Knowledge of the harmfulness of secondhand smoke was positively associated with
      support for smoke-free policies. Stricter worksite smoking policies were
      associated with support for smoke-free workplaces and bars, but not hotels and
      colleges. Women and nonsmokers were more supportive of smoke-free policies in
      general. CONCLUSION: Government workers play important roles in formulating,
      implementing and enforcing regulations; results suggest support for a more
      comprehensive approach to smoke-free environments in China among workers across a
      broad range of agencies.

PMID- 25367741
TI  - Simulation studies on the estimation of total area under the curve in the
      presence of right-tailed censoring.
AB  - The effect of extrapolated area (%AUCextrap) on estimating mean AUCinf in a
      simulated single-dose clinical trial was examined. Concentration-time (C-t)
      profiles from 12 to 36 subjects for 1- and 2-compartment models after single dose
      administration were simulated with increasing right-tailed censoring. Each
      subject's %AUCextrap and AUCinf was calculated using eight different methods,
      including noncompartmental analysis (NCA), population-based methods, and maximum
      likelihood (ML) accounting for censoring. Each method's geometric mean AUCinf and
      percent relative error (PRE) from the true AUCinf was calculated. This was
      repeated 100 times and the mean PRE (MPRE) was calculated. Mean %AUCextrap ranged
      from 1 to ~30 % for the 1-compartment and 2 to 32 % for the 2-compartment model
      at the lowest and highest degree of censoring, respectively. NCA methods using
      all subjects to estimate the population mean AUCinf had similar or less bias
      (within +/- 20 %) than when those subjects with >20 % %AUCextrap were removed.
      Using Cpred compared to Clast in the calculation of individual AUCinf resulted in
      no performance improvement. Linear mixed effects models to estimate lambdaz and
      ML methods accounting for censoring resulted in either no improvement or
      increased bias when censoring was high. Population pharmacokinetic method bias
      was dependent on the nature of the C-t profile. When the C-t profile declined
      biphasically, population models had higher bias than NCA methods but were
      superior when the C-t profile decline in a log-linear manner. It is recommended
      that subjects with high %AUCextrap should not be removed from the estimation of
      mean AUCinf in NCA analyses.

PMID- 25367742
TI  - Maternal HLA-C2 and 14 bp insertion in HLA-G is associated with recurrent
      implantation failure after in vitro fertilization treatment.
AB  - The major rate-limiting step in in vitro fertilization (IVF) success appears to
      be the implantation of the semi-allogeneic embryo into the maternal endometrium.
      To determine possible risk factors of recurrent failure of embryos to implant, we
      investigated immunogenetic determinants as level of human leukocyte antigen (HLA)
      histocompatibility, frequency of killer-cell immunoglobulin-like receptors (KIR)
      and HLA-C alleles and HLA-G polymorphism. We DNA typed women with recurrent
      implantation failure (RIF) and their partners for classical HLA Class I, HLA
      Class II, HLA-G and KIR alleles and compared these results with couples with
      successful embryo implantation after their first IVF and normal fertile couples.
      No association was found between RIF and the degree of histocompatibility between
      partners or sharing of a specific antigen. Also, no significant difference in KIR
      haplotype or combination of HLA-C group and KIR was observed. We did find a
      higher frequency of HLA-C2 and a higher frequency of 14 base pair (bp) insertion
      in HLA-G in women with RIF. Therefore we conclude that the degree of
      histocompatibility between partners is not a determining factor for the
      occurrence of RIF. However, presence of the HLA-C2 allotype and the HLA-G allele
      with a 14 bp insertion is a significant risk factor. 

PMID- 25367743
TI  - Construction of a synthetic infectious cDNA clone of Grapevine Algerian latent
      virus (GALV-Nf) and its biological activity in Nicotiana benthamiana and
      grapevine plants.
AB  - BACKGROUND: Grapevine Algerian latent virus (GALV) is a tombusvirus first
      isolated in 1989 from an Algerian grapevine (Vitis spp.) plant and more recently
      from water samples and commercial nipplefruit and statice plants. No further
      reports of natural GALV infections in grapevine have been published in the last
      two decades, and artificial inoculations of grapevine plants have not been
      reported. We developed and tested a synthetic GALV construct for the inoculation
      of Nicotiana benthamiana plants and different grapevine genotypes to investigate
      the ability of this virus to infect and spread systemically in different hosts.
      METHODS: We carried out a phylogenetic analysis of all known GALV sequences and
      an epidemiological survey of grapevine samples to detect the virus. A GALV-Nf
      clone under the control of the T7 promoter was chemically synthesized based on
      the full-length sequence of the nipplefruit isolate GALV-Nf, the only available
      sequence at the time the project was conceived, and the infectious transcripts
      were tested in N. benthamiana plants. A GALV-Nf-based binary vector was then
      developed for the agroinoculation of N. benthamiana and grapevine plants.
      Infections were confirmed by serological and molecular analysis and the resulting
      ultrastructural changes were investigated in both species. RESULTS: Sequence
      analysis showed that the GALV coat protein is highly conserved among diverse
      isolates. The first epidemiological survey of cDNAs collected from 152 grapevine
      plants with virus-like symptoms did not reveal the presence of GALV in any of the
      samples. The agroinoculation of N. benthamiana and grapevine plants with the GALV
      Nf binary vector promoted efficient infections, as revealed by serological and
      molecular analysis. The GALV-Nf infection of grapevine plants was characterized
      in more detail by inoculating different cultivars, revealing distinct patterns of
      symptom development. Ultrastructural changes induced by GALV-Nf in N. benthamiana
      were similar to those induced by tombusviruses in other hosts, but the
      cytopathological alterations in grapevine plants were less severe. CONCLUSIONS:
      This is the first report describing the development of a synthetic GALV-Nf cDNA
      clone, its artificial transmission to grapevine plants and the resulting symptoms
      and cytopathological alterations.

PMID- 25367744
TI  - Translation and validation of the Danish Foot Function Index (FFI-DK).
AB  - The objective of this study was to translate the Foot Function Index (FFI) for
      use in Danish-speaking patients with foot complaints. The FFI consists of 23
      items scored on a numeric rating scale from 0 to 10. The 23 items are grouped
      into three subscales: pain (nine items), activity limitation (five items), and
      disability (nine items). The Danish FFI was developed according to the
      recommended forward/backward translation protocol. The data analysis included
      reliability [intraclass correlation coefficient (ICC) 2.1] and internal
      consistency (Cronbach's alpha). Excellent internal consistency was shown for the
      three subscales: pain (0.99), disability (0.98), and activity limitation (0.98),
      as for the total score (0.97). The test-retest reliability was excellent: pain
      subscale: ICC 0.98 [95% confidence interval (CI): 0.97-0.99]; activity limitation
      subscale: ICC: 0.95 (95% CI: 0.91-0.98); disability subscale: ICC 0.97 (95% CI:
      0.95-0.98); total score: ICC: 0.95 (95% CI: 0.91 to 0.98). The mean difference
      between test and retest was below 1 point and P > 0.08. Bland-Altman plots showed
      no significant or clinically relevant differences from test to retest in any of
      the subscales or in the total score. The Danish version of the FFI was found to
      be valid and reliable and therefore acceptable for use in the Danish population. 

PMID- 25367745
TI  - Response to nab-paclitaxel plus gemcitabine in a patient with primary resistance
      to FOLFIRINOX.

PMID- 25367746
TI  - Ageing, adipose tissue, fatty acids and inflammation.
AB  - A common feature of ageing is the alteration in tissue distribution and
      composition, with a shift in fat away from lower body and subcutaneous depots to
      visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic
      site can have dramatic effects on metabolic function. In skeletal muscle,
      increased ectopic adiposity is linked to insulin resistance through lipid
      mediators such as ceramide or DAG, inhibiting the insulin receptor signalling
      pathway. Additionally, the risk of developing cardiovascular disease is increased
      with elevated visceral adipose distribution. In ageing, adipose tissue becomes
      dysfunctional, with the pathway of differentiation of preadipocytes to mature
      adipocytes becoming impaired; this results in dysfunctional adipocytes less able
      to store fat and subsequent fat redistribution to ectopic sites. Low grade
      systemic inflammation is commonly observed in ageing, and may drive the adipose
      tissue dysfunction, as proinflammatory cytokines are capable of inhibiting
      adipocyte differentiation. Beyond increased ectopic adiposity, the effect of
      impaired adipose tissue function is an elevation in systemic free fatty acids
      (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be
      regarded as the most detrimental of FFA, being capable of inducing insulin
      resistance and inflammation through lipid mediators such as ceramide, which can
      increase risk of developing atherosclerosis. Elevated FFA, in particular
      saturated fatty acids, maybe a driving factor for both the increased insulin
      resistance, cardiovascular disease risk and inflammation in older adults. 

PMID- 25367747
TI  - Prospective evaluation of a new protocol for the provisional use of perfusion
      imaging with exercise stress testing.
AB  - PURPOSE: Previous literature suggests that myocardial perfusion imaging (MPI)
      adds little to the prognosis of patients who exercise >10 metabolic equivalents
      (METs) during stress testing. With this in mind, we prospectively tested a
      provisional injection protocol in emergency department (ED) patients presenting
      for the evaluation of chest pain in which a patient would not receive an
      injection of radioisotope if adequate exercise was achieved without symptoms and
      a negative ECG response. METHODS: All patients who presented to the ED over a 5
      year period who were referred for stress testing as part of their ED evaluation
      were included. Patients considered for a provisional protocol were: exercise
      stress, age <65 years, no known coronary artery disease, and an interpretable
      rest ECG. Criteria for not injecting included a maximal predicted heart rate
      >=85%, >=10 METs of exercise, no anginal symptoms during stress, and no ECG
      changes. Groups were compared based on stress test results, all-cause and cardiac
      mortality, follow-up cardiac testing, subsequent revascularization, and cost.
      RESULTS: A total of 965 patients were eligible with 192 undergoing exercise-only
      and 773 having perfusion imaging. After 41.6 +/- 19.6 months of follow-up, all
      cause mortality was similar in the exercise-only versus the exercise plus imaging
      group (2.6% vs. 2.1%, p = 0.59). There were no cardiac deaths in the exercise
      only group. At 1 year there was no difference in the number of repeat functional
      stress tests (1.6% vs. 2.1%, p = 0.43), fewer angiograms (0% vs. 4.0%, p =
      0.002), and a significantly lower cost ($65 +/- $332 vs $506 +/- $1,991, p =
      0.002; values are in US dollars) in the exercise-only group. The radiation
      exposure in the exercise plus imaging group was 8.4 +/- 2.1 mSv. CONCLUSIONS: A
      provisional injection protocol has a very low mortality, few follow-up diagnostic
      tests, and lower cost compared to standard imaging protocols. If adopted it would
      decrease radiation exposure, save time and decrease health-care costs without
      jeopardizing prognosis.

PMID- 25367749
TI  - 18F-FDOPA PET/CT imaging of insulinoma revisited.
AB  - PURPOSE: (18)F-FDOPA PET imaging is increasingly used in the work-up of patients
      with neuroendocrine tumours. It has been shown to be of limited value in
      localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic
      hypoglycaemia (HH) mainly due to (18)F-FDOPA uptake by the whole pancreatic
      gland. The objective of this study was to review our experience with (18)F-FDOPA
      PET/CT imaging with carbidopa (CD) premedication in patients with HH in
      comparison with PET/CT studies performed without CD premedication in an
      independent population. METHODS: A retrospective study including 16 HH patients
      who were investigated between January 2011 and December 2013 using (18)F-FDOPA
      PET/CT (17 examinations) in two academic endocrine tumour centres was conducted.
      All PET/CT examinations were performed under CD premedication (200 mg orally, 1 -
      2 h prior to tracer injection). The PET/CT acquisition protocol included an early
      acquisition (5 min after (18)F-FDOPA injection) centred over the upper abdomen
      and a delayed whole-body acquisition starting 20 - 30 min later. An independent
      series of eight consecutive patients with HH and investigated before 2011 were
      considered for comparison. All patients had a reference whole-body PET/CT scan
      performed about 1 h after (18)F-FDOPA injection. In all cases, PET/CT was
      performed without CD premedication. RESULTS: In the study group, (18)F-FDOPA
      PET/CT with CD premedication was positive in 8 out of 11 patients with
      histologically proven insulinoma (73 %). All (18)F-FDOPA PET/CT-avid insulinomas
      were detected on early images and 5 of 11 (45 %) on delayed ones. The
      tumour/normal pancreas uptake ratio was not significantly different between early
      and delayed acquisitions. Considering all patients with HH, including those
      without imaging evidence of disease, the detection rate of the primary lesions
      using CD-assisted (18)F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17
      studies performed. In the control group (without CD premedication, eight
      patients), the final diagnosis was benign insulinoma in four, nesidioblastosis in
      one, and no definitive diagnosis in the remainder. (18)F-FDOPA PET/CT failed to
      detect any tumour in these patients. CONCLUSION: According to our experience, CD
      administration before (18)F-FDOPA injection leads to low residual pancreatic
      (18)F-FDOPA activity preserving tumoral uptake with consequent insulinoma
      detection in more than half of adult patients with HH and more than 70 % of
      patients with a final diagnosis of insulinoma. If (18)F-FDOPA PET/CT is
      indicated, we strongly recommend combining CD premedication with early
      acquisition centred over the pancreas.

PMID- 25367750
TI  - Extensive melorheostosis of the ribs demonstrated on 18F-Fluoride PET/CT.

PMID- 25367748
TI  - Nonsurgical giant cell tumour of the tendon sheath or of the diffuse type: are
      MRI or 18F-FDG PET/CT able to provide an accurate prediction of long-term
      outcome?
AB  - PURPOSE: To investigate whether MRI (RECIST 1.1, WHO criteria and the volumetric
      approach) or (18)F-FDG PET/CT (PERCIST 1.0) are able to predict long-term outcome
      in nonsurgical patients with giant cell tumour of the tendon sheath or of the
      diffuse type (GCT-TS/DT). METHODS: Fifteen "nonsurgical" patients with a
      histological diagnosis of GCT-TS/DT were divided into two groups: symptomatic
      patients receiving targeted therapy and asymptomatic untreated patients. All 15
      patients were evaluated by MRI of whom 10 were treated, and a subgroup of 7
      patients were evaluated by PET/CT of whom 4 were treated. Early evolution was
      assessed according to MRI and PET/CT scans at baseline and during follow-up.
      Cohen's kappa coefficient was used to evaluate the degree of agreement between
      PERCIST 1.0, RECIST 1.1, WHO criteria, volumetric approaches and the reference
      standard (long-term outcome, delay 505 +/- 457 days). The response rate in
      symptomatic patients with GCT-TS/DT receiving targeted therapy was also assessed
      in a larger population that included additional patients obtained from a review
      of the literature. RESULTS: The kappa coefficients for agreement between
      RECIST/WHO/volumetric criteria and outcome (15 patients) were respectively: 0.35
      (p = 0.06), 0.26 (p = 0.17) and 0.26 (p = 0.17). In the PET/CT subgroup (7
      patients), PERCIST was in perfect agreement with the late symptomatic evolution
      (kappa = 1, p < 0.05). In the treated symptomatic group including the additional
      patients from the literature the response rates to targeted therapies according
      to late symptomatic assessment, and PERCIST and RECIST criteria were: 65 %
      (22/34), 77 % (10/13) and 26 % (10/39). CONCLUSION: (18)F-FDG PET/CT with PERCIST
      is a promising approach to the prediction of the long-term outcome in GCT-TS/DT
      and may avoid unnecessary treatments, toxicity and costs. On MRI, WHO and
      volumetric approaches are not more effective than RECIST using the current
      thresholds.

PMID- 25367751
TI  - Squalene emulsion potentiates the adjuvant activity of the TLR4 agonist, GLA, via
      inflammatory caspases, IL-18, and IFN-gamma.
AB  - The synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) is a potent Th1
      response-inducing adjuvant when formulated in a squalene oil-in-water emulsion
      (SE). While the innate signals triggered by TLR4 engagement are well studied, the
      contribution of SE remains unclear. To better understand the effect of SE on the
      adjuvant properties of GLA-SE, we compared the innate and adaptive immune
      responses elicited by immunization with different formulations: GLA without oil,
      SE alone or the combination, GLA-SE, in mice. Within the innate response to
      adjuvants, only GLA-SE displayed features of inflammasome activation, evidenced
      by early IL-18 secretion and IFN-gamma production in memory CD8(+) T cells and
      neutrophils. Such early IFN-gamma production was ablated in caspase-1/11(-/-)
      mice and in IL-18R1(-/-) mice. Furthermore, caspase-1/11 and IL-18 were also
      required for full Th1 CD4(+) T-cell induction via GLA-SE. Thus, we demonstrate
      that IL-18 and caspase-1/11 are components of the response to immunization with
      the TLR4 agonist/squalene oil-in-water based adjuvant, GLA-SE, providing
      implications for other adjuvants that combine oils with TLR agonists. 

PMID- 25367752
TI  - Evolution of proline biosynthesis: enzymology, bioinformatics, genetics, and
      transcriptional regulation.
AB  - Proline is not only an essential component of proteins but it also has important
      roles in adaptation to osmotic and dehydration stresses, redox control, and
      apoptosis. Here, we review pathways of proline biosynthesis in the three domains
      of life. Pathway reconstruction from genome data for hundreds of eubacterial and
      dozens of archaeal and eukaryotic organisms revealed evolutionary conservation
      and variations of this pathway across different taxa. In the most prevalent
      pathway of proline synthesis, glutamate is phosphorylated to gamma-glutamyl
      phosphate by gamma-glutamyl kinase, reduced to gamma-glutamyl semialdehyde by
      gamma-glutamyl phosphate reductase, cyclized spontaneously to Delta(1)-pyrroline
      5-carboxylate and reduced to proline by Delta(1)-pyrroline-5-carboxylate
      reductase. In higher plants and animals the first two steps are catalysed by a bi
      functional Delta(1) -pyrroline-5-carboxylate synthase. Alternative pathways of
      proline formation use the initial steps of the arginine biosynthetic pathway to
      ornithine, which can be converted to Delta(1)-pyrroline-5-carboxylate by
      ornithine aminotransferase and then reduced to proline or converted directly to
      proline by ornithine cyclodeaminase. In some organisms, the latter pathways
      contribute to or could be fully responsible for the synthesis of proline. The
      conservation of proline biosynthetic enzymes and significance of specific
      residues for catalytic activity and allosteric regulation are analysed on the
      basis of protein structural data, multiple sequence alignments, and mutant
      studies, providing novel insights into proline biosynthesis in organisms. We also
      discuss the transcriptional control of the proline biosynthetic genes in bacteria
      and plants.

PMID- 25367753
TI  - Military Veterans' Experiences with Suicidal Ideation: Implications for
      Intervention and Prevention.
AB  - We sought to understand Operation Enduring Freedom and Operation Iraqi Freedom
      (OEF/OIF) veterans' experiences with suicidal ideation. Semi-structured
      interviews with 34 OEF/OIF veterans addressed circumstances leading up to
      disclosure of suicidal ideation during brief clinical assessments. We used an
      iterative, inductive and deductive thematic analysis approach. Results revealed
      three pervasive, persistent domains that reinforce the uniqueness of veteran
      suicidal thoughts: military culture, difficult deployment experiences, and
      postdeployment adjustment challenges. Within postdeployment, we identified four
      themes that serve as intervention targets: adjusting to civilian culture, changes
      to sense of self, feeling overwhelmed by stressors, and lacking life purpose or
      meaning. 

PMID- 25367754
TI  - Assessing the value of imperfect biocontainment nationally: rapeseed in the
      United Kingdom as an exemplar.
AB  - Paternal biocontainment methods (PBMs) act by preventing pollen-mediated
      transgene flow. They are compromised by transgene escape via the crop-maternal
      line. We therefore assess the efficacy of PBMs for transgenic rapeseed (Brassica
      napus) biocontainment across the United Kingdom by estimating crop-maternal
      hybridization with its two progenitor species. We used remote sensing, field
      surveys, agricultural statistics, and meta-analysis to determine the extent of
      sympatry between the crop and populations of riparian and weedy B. rapa and B.
      oleracea. We then estimated the incidence of crop-maternal hybridization across
      all settings to predict the efficacy of PBMs. Evidence of crop chloroplast
      capture by the progenitors was expanded to a national scale, revealing that crop
      maternal gene flow occurs at widely variable rates and is dependent on both the
      recipient and setting. We use these data to explore the value that this kind of
      biocontainment can bring to genetic modification (GM) risk management in terms of
      reducing the impact that hybrids have on the environment rather than preventing
      or reducing hybrid abundance per se. 

PMID- 25367757
TI  - Microfluidic system for high throughput characterisation of echogenic particles.
AB  - Echogenic particles, such as microbubbles and volatile liquid micro/nano
      droplets, have shown considerable potential in a variety of clinical diagnostic
      and therapeutic applications. The accurate prediction of their response to
      ultrasound excitation is however extremely challenging, and this has hindered the
      optimisation of techniques such as quantitative ultrasound imaging and targeted
      drug delivery. Existing characterisation techniques, such as ultra-high speed
      microscopy provide important insights, but suffer from a number of limitations;
      most significantly difficulty in obtaining large data sets suitable for
      statistical analysis and the need to physically constrain the particles, thereby
      altering their dynamics. Here a microfluidic system is presented that overcomes
      these challenges to enable the measurement of single echogenic particle response
      to ultrasound excitation. A co-axial flow focusing device is used to direct a
      continuous stream of unconstrained particles through the combined focal region of
      an ultrasound transducer and a laser. Both the optical and acoustic scatter from
      individual particles are then simultaneously recorded. Calibration of the device
      and example results for different types of echogenic particle are presented,
      demonstrating a high throughput of up to 20 particles per second and the ability
      to resolve changes in particle radius down to 0.1 MUm with an uncertainty of less
      than 3%. 

PMID- 25367758
TI  - Characterization of a new HLA-B allele, B*15:179:02.
AB  - A novel HLA-B allele, B*15:179:02, has been identified during typing of donors in
      Anhui province, China. 

PMID- 25367759
TI  - Protection or cytotoxicity mediated by a novel quinonoid-polyphenol compound?
AB  - Many natural and synthetic quinones and naphthoquinones possess a variety of
      beneficial pharmacological properties. In plants, the cytotoxic properties of
      quinones serve in their defensive roles against invading bacteria, fungi and
      parasites. In this regard many quinones as well as polyphenols, exerting
      generally toxicity at high dosages, are able to induce favorable hormetic
      responses at a low dosage. The novel chloronaphthoquinone derivative of quercetin
      (CHNQ) showed a profound cytotoxicity followed by enhancement of intracellular
      generation of oxidants in human neonatal B-HNF-3 fibroblasts. Its synthetic
      precursors, quercetin and 2-chloro-3-hydroxy-[1,4]naphthoquinone, failed to
      induce these effects, and paradoxically, only CHNQ at a low concentration
      provided partial protection of the cells against oxidative challenge. Thus, the
      novel quinonoid-polyphenol CHNQ might have a merit in the search for new
      prospective agents in prevention and management of ageing and ageing-related
      pathologies.

PMID- 25367760
TI  - Role of resveratrol on the cytotoxic effects and DNA damages of iododeoxyuridine
      and megavoltage radiation in spheroid culture of U87MG glioblastoma cell line.
AB  - The purpose of this study was to evaluate the effect of resveratrol on
      cytogenetic damages of iododeoxyuridine (IUdR) and x-ray megavoltage radiation (6
      MV) in spheroid model of U87MG glioblastoma cancer cell line using clonogenic and
      alkaline comet assay. Cells were cultured as spheroids (350 um) that were treated
      with 20 MUM resveratrol, 1 MUM IUdR and 2 Gy of 6 MV x-ray. After treatment,
      viability of the cells, colony forming ability and the induced DNA damages were
      examined using trypan blue dye exclusion, colonogenic and alkaline comet assay,
      respectively. Our results showed that resveratrol could significantly reduce the
      colony number and induce the DNA damages of the cells treated with IUdR in
      combination with 6 MV x-ray radiation. That results indicated that resveratrol as
      an inhibitor of hypoxia inducible factor 1 alpha (HIF-1alpha) protein in
      combination with IUdR as a radiosensitizer enhanced the radiosensitization of
      glioblastoma spheroid cells. 

PMID- 25367761
TI  - Functional changes in piriform cortex pyramidal neurons in the chronic
      methamphetamine-treated rat.
AB  - Chronic treatment of rats with methamphetamine (MAP) causes a range of functional
      changes to the central nervous system (CNS), including a toxicity that is
      widespread throughout the brain (Frost and Cadet 2000; Fasihpour et al. 2013). In
      this report, we examined the effect of chronic MAP treatment on pyramidal neurons
      of the rat piriform cortex, an area involved in sensory processing, associative
      learning and a model system for studies on synaptic plasticity. MAP treatment
      significantly depolarized the membrane potential and decreased neuronal input
      resistance. Furthermore, the voltage-dependence of both AMPA and NMDA responses
      was disturbed by chronic MAP treatment, and the extent of long-term potentiation
      (LTP) was decreased. Morphological changes of MAP-treated rat pyramidal neurons
      were observed as blebbing of the dendrite trees. The changes we observed
      represent detrimental effects on the function of piriform cortical neurons
      further illustrating deficits in synaptic plasticity extend beyond the
      hippocampus. These changes may contribute to behavioural deficits in chronic MAP
      treated animals. 

PMID- 25367762
TI  - Influence of oak wood polyphenols on cysteine, homocysteine and glutathione total
      levels and PON1 activities in human adult volunteers - a pilot study.
AB  - Oxidative stress reflects an imbalance between antioxidants and pro-oxidants.
      Many diseases like atherosclerosis or heart failure are involved in oxidative
      stress. Increased oxidative stress is one of the potential contributing factors
      to aging. The aim of this study was to monitor the total thiol levels as markers
      of oxidative stress in 20 healthy volunteers after polyphenols intake (extract
      from the French oak wood Quercus robur - Robuvit(r) (300 mg/day)). Polyphenols
      are known as biomodulators with antioxidant activities. Homocysteine, cysteine
      and glutathione total levels were determined by using HPLC with electrochemical
      detection. The activity of the antioxidant enzyme paraoxonase-1 toward two
      substrates was determined by spectrophotometry. The level of thiol compounds and
      paraoxonase-1 activities were controlled after run-in (week 0), intervention
      (week 4) and washout (week 6) period. After the intervention period the results
      showed that Robuvit(r) had no significant influence on glutathione level (p =
      0.382) and paraoxonase activities towards both, arylester and lactone substrates.
      On the other hand, homocysteine and cysteine levels decreased significantly (p =
      0.029; p < 0.001, respectively). The negative correlation between paraoxonase
      lactonase activity and homocysteine level was noticed. This confirms that
      paraoxonase might play an important role in homocysteine-thiolactone metabolism. 

PMID- 25367763
TI  - Differential impact of bortezomib on HL-60 and K562 cells.
AB  - Bortezomib (PS-341, or Velcade), reversible inhibitor of 20S proteasome approved
      for the treatment of multiple myeloma and mantle cell lymphoma, exhibited a
      cytotoxic effect toward other malignancies including leukaemia. In this study, we
      have documented that incubation of both HL-60 and K562 leukaemia cells with
      nanomolar concentrations of bortezomib is associated with the death of HL-60
      cells observed within 24 hours of incubation with bortezomib and the death of
      K562 cells that were observed after 72 hours of incubation with bortezomib. The
      relative resistance of K562 cells to bortezomib correlated well with
      significantly higher expression of HSP27, HSP70, HSP90alpha, HSP90beta and GRP75
      in these cells. Incubation of both HL-60 and K562 cells with bortezomib induced a
      cleavage of HSP90beta as well as expression of HSP70 and HSP90beta but bortezomib
      did not affect levels of HSP27, HSP90alpha, GRP75 and GRP78. The death of both
      types of cells was accompanied with proteolytic activation of caspase 3 that was
      observed in HL-60 cells and proteolytic degradation of procaspase 3 in K562
      cells. Our study has also pointed to essential role of caspase 8 in bortezomib
      induced cleavage of HSP90beta in both HL-60 and K562 cells. Finally, we have
      shown that bortezomib induced activation of caspase 9/caspase 3 axis in HL-60
      cells, while the mechanism of death of K562 cells remains unknown. 

PMID- 25367765
TI  - Erratum to: The Incidence of Melanoma is Increasing in the Susceptible Young
      Australian Population. Acta Derm Venereol 2014; 94: 539-541.

PMID- 25367764
TI  - Thymoquinone supplementation reverses lead-induced oxidative stress in adult rat
      testes.
AB  - The purpose of the present study was to investigate the potential protective
      effect of thymoquinone (TQ), the major active ingredient of volatile oil of
      Nigella sativa seeds, against Pb-induced testicular oxidative stress. Adult male
      rats were randomized into four groups: control group which received no treatment,
      Pb group was exposed to 2000 ppm Pb acetate in drinking water, Pb-TQ group was co
      treated with Pb plus TQ (5 mg/kg b.w./day, p.o.) and TQ group receiving only TQ
      (5 mg/kg b.w./day, p.o.). All treatments were applied for 5 weeks. Pb treatment
      induced oxidative stress status in testes as evidenced by a significant decrease
      in the antioxidant enzymes activities such as superoxide dismutase, glutathione
      peroxidase and catalase, and in the reduced glutathione content and in a
      significant increase in the level of malondialdehyde. Interestingly, TQ
      supplementation completely reversed these biochemical changes caused by Pb to the
      control values. In conclusion, our results suggest, for the first time, that TQ
      is very efficient in preventing Pb-induced testicular oxidative stress. This
      study will open new perspectives for the clinical use of TQ in Pb intoxication. 

PMID- 25367766
TI  - Recurrence quantification analysis of electroencephalograph signals during
      standard tasks of Waterloo-Stanford group scale of hypnotic susceptibility.
AB  - The purpose of this study was to apply RQA (recurrence quantification analysis)
      on hypnotic electroencephalograph (EEG) signals recorded after hypnotic induction
      while subjects were doing standard tasks of the Waterloo-Stanford Group Scale
      (WSGS) of hypnotic susceptibility. Then recurrence quantifiers were used to
      analyse the influence of hypnotic depth on EEGs. By the application of this
      method, the capability of tasks to distinguish subjects of different
      hypnotizability levels was determined. Besides, medium hypnotizable subjects
      showed the highest disposition to be inducted by hypnotizer. Similarities between
      brain governing dynamics during tasks of the same type were also observed. The
      present study demonstrated two remarkable innovations; investigating the EEGs of
      the hypnotized as doing mental tasks of Waterloo-Stanford Group Scale (WSGS) and
      applying RQA on hypnotic EEGs.

PMID- 25367767
TI  - Paraneoplastic subacute cutaneous lupus erythematosus associated with
      cholangiocarcinoma.
AB  - Subacute cutaneous lupus erythematosus (SCLE) is a dermatosis that occurs in
      genetically predisposed individuals. The exogenous stimulus that triggers this
      condition is usually unknown; however, medication is often implicated. Malignancy
      is a rare cause. We present a case of paraneoplastic SCLE to cholangiocarcinoma
      and briefly review the features of this interesting entity. 

PMID- 25367768
TI  - Public knowledge of cardiovascular disease and its risk factors in Kuwait: a
      cross-sectional survey.
AB  - BACKGROUND: Cardiovascular disease (CVD) is estimated to cause 46% of all
      mortalities in Kuwait. To design effective primary and secondary prevention
      programs, an assessment of a population's prior CVD knowledge is of paramount
      importance. There is scarcity of data on the existing CVD knowledge among the
      general Kuwaiti population. Hence, this study was performed to assess the level
      of knowledge towards CVD types, warning symptoms of heart attack or stroke, and
      CVD risk factors. It also explored public views on the community pharmacists'
      role in CVD prevention and management. METHODS: A descriptive cross-sectional
      survey was performed using a pretested self-administered questionnaire on a
      sample of 900 randomly selected Kuwaiti individuals. Descriptive and multivariate
      logistic regression analysis were used in data analysis. RESULTS: The response
      rate was 90.7%. Respondents' knowledge about types of CVD, heart attack or stroke
      symptoms was low. Almost 60% of respondents did not know any type of CVD, and
      coronary heart disease was the commonest identified type (29.0%). Two-fifths of
      participants were not aware of any heart attack symptoms, and the most commonly
      known were chest pain (50.4%) and shortness of breath (48.0%). Approximately half
      of respondents did not recognize any stroke symptoms, and the most commonly
      recognized were 'confusion or trouble speaking' (36.4%) and 'numbness or
      weakness' (34.7%). Respondents' knowledge regarding CVD risk factors was
      moderate. The commonest factors identified by over four-fifths of participants
      were smoking, obesity, unhealthy diet and physical inactivity. In the
      multivariate logistic regression analysis, independent predictors of better level
      of CVD knowledge were females, age 50-59 years, high level of education, regular
      eating of healthy diet, and had a family history of CVD. Most of respondents only
      identified the role that pharmacists had to play is to help patients manage their
      medications, with a minimal role in other aspects of CVD prevention and
      management. CONCLUSIONS: There are deficiencies in CVD knowledge among Kuwaiti
      population, which could turn into insufficient preventative behaviours and
      suboptimal patient outcomes. There is an apparent need to establish more wide
      spread and effective educational interventions, which should be sensitive to the
      perceptions, attitudes, and abilities of targeted individuals.

PMID- 25367770
TI  - BWH emergency radiology-surgical correlation: pancreatic laceration.
AB  - We describe the radiological and intraoperative correlation of pancreatic
      laceration in a 76-year-old unrestrained motor-vehicle driver following blunt
      abdominal trauma. The purpose of this article is to emphasize the importance of
      recognizing pancreatic injuries in trauma patients, as these injuries are rare
      and can be overlooked on CT. 

PMID- 25367771
TI  - Evaluation of a focused virtual library of heterobifunctional ligands for
      Clostridium difficile toxins.
AB  - A focused library of virtual heterobifunctional ligands was generated in silico
      and a set of ligands with recombined fragments was synthesized and evaluated for
      binding to Clostridium difficile toxins. The position of the trisaccharide
      fragment was used as a reference for filtering docked poses during virtual
      screening to match the trisaccharide ligand in a crystal structure. The peptoid,
      a diversity fragment probing the protein surface area adjacent to a known binding
      site, was generated by a multi-component Ugi reaction. Our approach combines
      modular fragment-based design with in silico screening of synthetically feasible
      compounds and lays the groundwork for future efforts in development of composite
      bifunctional ligands for large clostridial toxins. 

PMID- 25367772
TI  - Development and validation of a new technique for estimating a minimum postmortem
      interval using adult blow fly (Diptera: Calliphoridae) carcass attendance.
AB  - Understanding the onset and duration of adult blow fly activity is critical to
      accurately estimating the period of insect activity or minimum postmortem
      interval (minPMI). Few, if any, reliable techniques have been developed and
      consequently validated for using adult fly activity to determine a minPMI. In
      this study, adult blow flies (Diptera: Calliphoridae) of Cochliomyia macellaria
      and Chrysomya rufifacies were collected from swine carcasses in rural central
      Texas, USA, during summer 2008 and Phormia regina and Calliphora vicina in the
      winter during 2009 and 2010. Carcass attendance patterns of blow flies were
      related to species, sex, and oocyte development. Summer-active flies were found
      to arrive 4-12 h after initial carcass exposure, with both C. macellaria and C.
      rufifacies arriving within 2 h of one another. Winter-active flies arrived within
      48 h of one another. There was significant difference in degree of oocyte
      development on each of the first 3 days postmortem. These frequency differences
      allowed a minPMI to be calculated using a binomial analysis. When validated with
      seven tests using domestic and feral swine and human remains, the technique
      correctly estimated time of placement in six trials.

PMID- 25367774
TI  - The correlation between biofilm biopolymer composition and membrane fouling in
      submerged membrane bioreactors.
AB  - Biofouling, the combined effect of microorganism and biopolymer accumulation,
      significantly reduces the process efficiency of membrane bioreactors (MBRs).
      Here, four biofilm components, alpha-polysaccharides, beta-polysaccharides,
      proteins and microorganisms, were quantified in MBRs. The biomass of each
      component was positively correlated with the transmembrane pressure increase in
      MBRs. Proteins were the most abundant biopolymer in biofilms and showed the
      fastest rate of increase. The spatial distribution and co-localization analysis
      of the biofouling components indicated at least 60% of the extracellular
      polysaccharide (EPS) components were associated with the microbial cells when the
      transmembrane pressure (TMP) entered the jump phase, suggesting that the EPS
      components were either secreted by the biofilm cells or that the deposition of
      these components facilitated biofilm formation. It is suggested that biofilm
      formation and the accumulation of EPS are intrinsically coupled, resulting in
      biofouling and loss of system performance. Therefore, strategies that control
      biofilm formation on membranes may result in a significant improvement of MBR
      performance. 

PMID- 25367775
TI  - Xylan degradation improved by a combination of monolithic columns bearing
      immobilized recombinant beta-xylosidase from Aspergillus awamori X-100 and
      Grindamyl H121 beta-xylanase.
AB  - Synergistic action of exo- and endohydrolazes is preferred for effective
      destruction of biopolymers. The main purpose of the present work was to develop
      an efficient tool for degradation of xylan. Macroporous lab-made monolithic
      columns and commercial CIM-Epoxy disk were used to immobilize the recombinant
      beta-xylosidase from Aspergillus awamori and Grindamyl beta-xylanase. The
      efficiency of xylan degradation using the low-loaded beta-xylosidase column
      appeared to be four times higher than for the in-solution process and about six
      times higher than for the high-loaded bioreactor. Disk bioreactor with the
      Grindamil beta-xylanase operated in a recirculation mode has shown noticeable
      advantages over the column design. Additionally, a system comprised of two
      immobilized enzyme reactors (IMERs) was tested to accelerate the biopolymer
      hydrolysis, yielding total xylan conversion into xylose within 20 min. Fast
      online monitoring HPLC procedure was developed where an analytical DEAE CIM disk
      was added to the two-enzyme system in a conjoint mode. A loss of activity of
      immobilized enzymes did not exceed 7% after 5 months of the bioreactor usage. We
      can therefore conclude that the bioreactors developed exhibit high efficiency and
      remarkable long-term stability. 

PMID- 25367776
TI  - Transfer of aryl halide to alkyl halide: reductive elimination of alkylhalide
      from alkylpalladium halides containing syn-beta-hydrogen atoms.
AB  - beta-Hydride abstraction is a well-accepted elementary step for catalytic cycles
      in organometallic chemistry. It is usually anticipated that alkylpalladium
      halides containing syn-beta-hydrogen atoms will undergo beta-hydride abstraction
      to afford the Heck-type products. However, this study discloses that the above
      general knowledge is only conditionally correct. Our experimental results
      demonstrate that the reductive elimination of alkylhalides from alkylpalladium
      halides containing syn-beta-hydrogen atoms may surpass the beta-hydride
      abstraction or even become exclusive in certain cases. 

PMID- 25367773
TI  - Mitochondrial targets for pharmacological intervention in human disease.
AB  - Over the past several years, mitochondrial dysfunction has been linked to an
      increasing number of human illnesses, making mitochondrial proteins (MPs) an ever
      more appealing target for therapeutic intervention. With 20% of the mitochondrial
      proteome (312 of an estimated 1500 MPs) having known interactions with small
      molecules, MPs appear to be highly targetable. Yet, despite these targeted
      proteins functioning in a range of biological processes (including induction of
      apoptosis, calcium homeostasis, and metabolism), very few of the compounds
      targeting MPs find clinical use. Recent work has greatly expanded the number of
      proteins known to localize to the mitochondria and has generated a considerable
      increase in MP 3D structures available in public databases, allowing experimental
      screening and in silico prediction of mitochondrial drug targets on an
      unprecedented scale. Here, we summarize the current literature on clinically
      active drugs that target MPs, with a focus on how existing drug targets are
      distributed across biochemical pathways and organelle substructures. Also, we
      examine current strategies for mitochondrial drug discovery, focusing on genetic,
      proteomic, and chemogenomic assays, and relevant model systems. As cell models
      and screening techniques improve, MPs appear poised to emerge as relevant targets
      for a wide range of complex human diseases, an eventuality that can be expedited
      through systematic analysis of MP function. 

PMID- 25367777
TI  - Chronic diclofenac (DCF) exposure alters both enzymatic and haematological
      profile of African catfish, Clarias gariepinus.
AB  - Pharmaceuticals are used extensively in human and veterinary medicine to
      eradicate or prevent diseases. The residues of these drugs have been detected in
      aquatic ecosystem; nevertheless, their toxicological effects on Clarias
      gariepinus have not been critically investigated. In this study, the toxic
      effects of diclofenac (DCF), a non-steroid anti-inflammatory drug, were studied
      in C. gariepinus by acute and chronic static renewable bioassay. The 96 h LC50 of
      DCF to C. gariepinus was 25.12 mg/L. Exposure to acute toxicity resulted in
      abnormal behavior and mortality of some fish. Compared with the control, chronic
      exposure of the fish to concentration (1.57, 3.14 and 6.28 mg/L) showed
      significantly higher mean corpuscular haemoglobin concentration (MCHC), mean
      corpuscular volume (MCV) and white blood cell (WBC), with significantly lower
      haemoglobin (Hb), haematocrit, red blood cell (RBC) and mean corpuscular
      haemoglobin (MCH) with increase in the concentration of the drug. Furthermore,
      the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      lactate dehydrogenase (LDH) and glucose values significantly increased while
      protein levels were reduced (p < 0.05) in serum and gills throughout the 42-day
      exposure period. The study reports that DCF-induced enzymatic and haematological
      changes in the fish and recommends that these parameters be used as potential
      biomarkers for assessing residual pharmaceuticals available in aquatic ecosystem.

PMID- 25367778
TI  - Combined repeated dose and reproductive/developmental toxicity screening test of
      4-methoxy-2-nitroaniline in rats.
AB  - 4-Methoxy-2-nitroaniline (4M2NA) is widely used as an intermediate for the
      synthesis of dyes, pigments and other chemical compounds. Since 4M2NA has amino
      group and nitro-group on the benzene ring, it was expected that it induced
      obvious hemolytic anemia. We conducted a combined repeated dose and
      reproductive/developmental toxicity screening test according to Organisation for
      Economic Co-operation and Development (OECD) Test Guideline No. 422 (OECD TG 422)
      to enrich the toxic information and ensure the safety of 4M2NA. 4M2NA was
      administered to Crl:CD(SD) male and female rats by gavage at 0, 12.5, 75 or 450
      mg/kg/day for 42 to maximum of 54 days through pre-mating, mating, pregnancy and
      lactation periods. An extramedullary hematopoiesis and congestion in spleen, and
      higher reticulocyte ratio were noted in only females at 450 mg/kg/day without
      decreased anemic parameters in the hematological examination. Hypertrophy of
      centrilobular hepatocytes in both sexes was observed with increased relative
      liver weight at 450 mg/kg/day. Furthermore, the diffuse follicular cell
      hypertrophy of the thyroid was observed in females at 450 mg/kg/day. No
      abnormalities were detected in the reproductive indices of copulation, delivery
      or fetal viability. We concluded the no-observed-adverse-effect level (NOAEL) for
      repeated-dose toxicity was 75 mg/kg/day based on the trace evidences of hemolytic
      anemia, and the NOAEL for reproductive/developmental toxicity as 450 mg/kg/day
      based on no toxicological concerns for reproductive endpoints. The hemolytic
      anemia was much milder than expected. Thus, we discussed the reason of this much
      less hemolytic effect from the point of view of the structural characteristics of
      4M2NA. 

PMID- 25367779
TI  - Asymmetric synthesis of allylic sulfonic acids: enantio- and regioselective
      iridium-catalyzed allylations of Na2SO3.
AB  - An enantioselective allylation reaction of allylic carbonates with sodium sulfite
      (Na2 SO3 ) catalyzed by Ir complex was accomplished, providing allylic sulfonic
      acids in good to excellent yields with a high level of enantio- and
      regioselectivities. (R)-2-Phenyl-2-sulfoacetic acid, a key intermediate for the
      synthesis of Cefsulodin and Sulbenicillin, was synthesized as well. 

PMID- 25367780
TI  - Comparison between simulated decoupling regimes for specific absorption rate
      prediction in parallel transmit MRI.
AB  - PURPOSE: The use of electromagnetic (EM) modeling is critical for specific
      absorption rate (SAR) characterization in parallel transmission MRI.
      Radiofrequency arrays that include decoupling networks can be difficult to
      characterize accurately in simulation. A practical method of simplifying modeling
      is to exclude the decoupling networks and model each transmit element in
      isolation. Results from this type of model can be related to a real device by
      applying "active decoupling" to the real device to suppress residual coupling
      when in use. Here, we compare this approach with a full model that includes
      decoupling networks. METHODS: EM simulations for a variety of adult male voxel
      models placed within an eight-channel transverse electromagnetic (TEM) array
      tuned for 3 Tesla operation were run with and without decoupling networks
      included. The resulting EM fields and SAR estimates were compared using basic
      normalization, and simulated active decoupling. RESULTS: Modeling the transmit
      elements independently leads to variations which have significantly different SAR
      estimates of ~20% on average compared with the full model if not normalized
      appropriately. After "active decoupling," SAR was still generally seen to be
      overestimated by ~7% with independent channel modeling; despite having similar
      B1(+) field distributions. CONCLUSION: Modeling transmission elements
      independently may lead to substantially incorrect SAR estimates if the
      corresponding MRI system is not run in an analogous manner.

PMID- 25367781
TI  - Multi-responsive cellulose nanocrystal-rhodamine conjugates: an advanced
      structure study by solid-state dynamic nuclear polarization (DNP) NMR.
AB  - Multi-stimuli responsive materials based on cellulose nanocrystals (CNCs),
      especially using non-conventional stimuli including light, still need more
      explorations, to fulfill the requirements of complicated application
      environments. The structure determination of functional groups on the CNC surface
      constitutes a significant challenge, partially due to their low amounts. In this
      study, rhodamine spiroamide groups are immobilized onto the surface of CNCs
      leading to a hybrid compound being responsive to pH-values, heat and UV light.
      After the treatment with external stimuli, the fluorescent and correlated optical
      color change can be induced, which refers to a ring opening and closing process.
      Amine and amide groups in rhodamine spiroamide play the critical role in this
      switching process. Solid-state NMR spectroscopy coupled with sensitivity-enhanced
      dynamic nuclear polarization (DNP) was used to measure (13)C and (15)N in natural
      abundance, allowing the determination of structural changes during the switching
      process. It is shown that a temporary bond through an electrostatic interaction
      could be formed within the confined environment on the CNC surface during the
      heat treatment. The carboxyl groups on the CNC surface play a pivotal role in
      stabilizing the open status of rhodamine spiroamide groups. 

PMID- 25367782
TI  - Inhibition of the hyaluronan oligosaccharides inflammatory response: reduction of
      adenosine 2A receptor activation by EPAC and PKA.
AB  - The aim of this study was to investigate the involvement of exchange proteins
      directly activated by cyclic adenosine (ADO) monophosphate (EPAC) in 4-mer
      hyaluronan (HA) oligosaccharide-induced inflammatory response in mouse normal
      synovial fibroblasts (NSF). Treatment of NSF with 4-mer HA increased Toll-like
      receptor-4, TNF-alpha and IL-1beta mRNA expression and of the related proteins,
      as well as nuclear factor kappaB (NF-kB) activation. Addition to NSF, previously
      stimulated with 4-mer HA oligosaccharides, of ADO significantly reduced NF-kB
      activation, TNF-alpha and IL-1beta expression. The pre-treatment of NSF with
      cyclic ADO monophosphate and/or PKA and/or EPAC-specific inhibitors significantly
      inhibited the anti-inflammatory effect exerted by ADO. In particular, the EPAC
      inhibitor reduced the ADO effect to a major extent than the PKA inhibitor. These
      results mean that both PKA and EPAC pathways are involved in ADO-induced NF-kB
      inhibition although EPAC seems to be more involved than PKA.

PMID- 25367783
TI  - Bioinformatics analysis of Rab GDP dissociation inhibitor beta and its expression
      in non-small cell lung cancer.
AB  - BACKGROUND: Lung cancer has been considered as one of the most important causes
      of cancer-related mortality worldwide. To predict lung cancer, researchers
      identified several molecular markers. However, many underlying markers of lung
      cancer remain unclear. One of these markers is Rab GDP dissociation inhibitor
      beta (GDIbeta), which is related to tumorigenicity, development and invasion.
      This study was designed to analyze the biological characteristics of Rab GDIbeta
      and to detect the mRNA and protein expressions of Rab GDIbeta in lung cancer
      cells; this study also aimed to investigate the functions of this protein in lung
      cancer. METHOD: Using online software from the websites of NCBI, ProtParam and so
      on, we analyzed the biological characteristics of Rab GDIbeta. RT-PCR was
      performed to detect gene expressions in A549 and 16HBE cell lines and
      immunohistochemistry (IHC) staining was conducted to detect Rab GDIbeta protein
      expression in 57 cases of human lung cancer tissues and 19 cases of normal lung
      tissues. The association of protein expression with patient clinical and
      pathological characteristics was assessed in each dataset. RESULTS: Bioinformatic
      analysis on Rab GDIbeta: The mRNA of human Rab GDIbeta contains two transcript
      variants; the common structural elements of the two proteins are mainly alpha
      helix, random coil, beta-turn and extended strand. Three and four transmembrane
      domains could be found in the entire polypeptide chain of protein variants 1 and
      2, respectively; both transcript variants are hydrophilic and soluble proteins.
      The RT-PCR result: The mRNA expression of Rab GDIbeta was down-regulation in A549
      cells compared with that in 16HBE cells. The IHC result: The protein expression
      of Rab GDIbeta in lung cancer cells was significantly lower than that in normal
      lung tissues (P <0.05) but was not correlated with patients' age, gender, tumor
      size, pathological type, differentiation, lymph node metastasis, distant
      metastasis and TNM stage. CONCLUSION: The expression of Rab GDIbeta was low in
      non-small cell lung cancer (NSCLC). Hence, Rab GDIbeta may be a tumor suppressor
      and could function as an indicator of tumorigenesis in NSCLC; nevertheless, this
      result should be further studied. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_201.

PMID- 25367784
TI  - Encoding and retrieval along the long axis of the hippocampus and their
      relationships with dorsal attention and default mode networks: The HERNET model.
AB  - The encoding of sensory input is intertwined with external attention, whereas
      retrieval is intrinsically related to internal attention. This study proposes a
      model in which the encoding of sensory input involves mainly the anterior
      hippocampus and the external attention network, whereas retrieval, the posterior
      hippocampus and the internal attention network. This model is referred to as the
      HERNET (hippocampal encoding/retrieval and network) model. Functional
      neuroimaging studies have identified two intrinsic large-scale networks closely
      associated with external and internal attention, respectively. The dorsal
      attention network activates during any externally oriented mental activity,
      whereas the default mode network shows increased activity during internally
      oriented mental activity. Therefore, the HERNET model may predict the activation
      of the anterior hippocampus and the dorsal attention network during the encoding
      and activation of the posterior hippocampus and the default mode network during
      retrieval. To test this prediction, this study provides a meta-analysis of three
      memory-imaging paradigms: subsequent memory, laboratory-based recollection, and
      autobiographical memory retrieval. The meta-analysis included 167 individual
      studies and 2,856 participants. The results provide support for the HERNET model
      and suggest that the anterior-posterior gradient of encoding and retrieval
      includes amygdala regions. More broadly, humans continuously oscillate between
      external and internal attention and thus between encoding and retrieval
      processes. These oscillations may involve repetitive and spontaneous activity
      switching between the anterior hippocampus/dorsal attention network and the
      posterior hippocampus/default mode network.

PMID- 25367785
TI  - Three-dimensional nitrogen-doped graphene nanoribbons aerogel as a highly
      efficient catalyst for the oxygen reduction reaction.
AB  - A highly conductive, ultralight, neat and versatile nitrogen-doped GNRs aerogel
      has been fabricated by a new hydrothermal method for the first time. The newly
      developed aerogel shows a very promising performance when used as a novel ORR
      catalyst in both alkaline and acidic solutions. 

PMID- 25367786
TI  - Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat
      plasma after oral administration of Ginkgo biloba tablets: application to a
      pharmacokinetic study.
AB  - A rapid, reliable, and sensitive method was developed using ultra-performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with an electrospray
      ionization (ESI) source for determination of seven bioactive compounds in rat
      plasma after oral administration of Ginkgo biloba tablets (GBTs). The method
      simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB),
      ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for
      pharmacokinetic study. The analytes and internal standard (IS) were extracted
      from rat plasma by acetidin. An MS/MS detection was conducted using multiple
      reaction monitoring (MRM) and operating in the negative ionization mode. The
      calibration curve ranges were 5-500, 5-500, 2.5-250, 1-100, 1-100, 1-100, and 1
      100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery
      of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions
      were in the range of 2.33%-9.86% and the accuracies were between 87.67% and
      108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The
      pharmacokinetic parameters of seven compounds were analyzed using a non
      compartment model. Plasma concentrations of the seven compounds were determined
      up to 48 h after administration, and their pharmacokinetic parameters were in
      agreement with previous studies. 

PMID- 25367787
TI  - Essential oil from Zanthoxylum bungeanum Maxim. and its main components used as
      transdermal penetration enhancers: a comparative study.
AB  - Our previous studies had confirmed that the essential oil from Zanthoxylum
      bungeanum Maxim. (Z. bungeanum oil) could effectively enhance the percutaneous
      permeation of drug molecules as a natural transdermal penetration enhancer. The
      aim of the present study is to investigate and compare the skin penetration
      enhancement effect of Z. bungeanum oil and its main components on traditional
      Chinese medicine (TCM) active components. Toxicities of Z. bungeanum oil and
      three selected terpene compounds (terpinen-4-ol, 1,8-cineole, and limonene) in
      epidermal keratinocytes (HaCaT) and dermal fibroblast (CCC-ESF-1) cell lines were
      measured using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) assay. Five model drugs in TCM external preparations, namely osthole
      (OT), tetramethylpyrazine (TMP), ferulic acid (FA), puerarin (PR), and geniposide
      (GP), which were selected based on their lipophilicity denoted by logKo/w, were
      tested using in vitro permeation studies in which vertical Franz diffusion cells
      and rat abdominal skin were employed. The secondary structure changes of skin
      stratum corneum (SC) and drug thermodynamic activities were investigated to
      understand their mechanisms of action using Fourier transform infrared (FTIR)
      spectroscopy and saturation solubility studies, respectively. It was found that
      Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells
      compared with three terpene compounds used alone. The enhancement permeation
      capacities by all tested agents were in the following increasing order: terpinen
      4-ol~1,8-cineole<limonene<Z. bungeanum oil. The mechanisms of permeation
      enhancement suggested that these enhancers promoted the skin permeation of drugs
      mainly by affecting SC lipids. These results indicated that Z. bungeanum oil
      exhibited better performance in enhancing the skin permeation of active
      components in TCM preparations. 

PMID- 25367788
TI  - Temporal changes in soil bacterial and archaeal communities with different
      fertilizers in tea orchards.
AB  - It is important to understand the effects of temporal changes in microbial
      communities in the acidic soils of tea orchards with different fertilizers. A
      field experiment involving organic fertilizer (OF), chemical fertilizer (CF), and
      unfertilized control (CK) treatments was arranged to analyze the temporal changes
      in the bacterial and archaeal communities at bimonthly intervals based on the 16S
      ribosomal RNA (rRNA) gene using terminal restriction fragment length polymorphism
      (T-RFLP) profiling. The abundances of total bacteria, total archaea, and selected
      functional genes (bacterial and archaeal amoA, bacterial narG, nirK, nirS, and
      nosZ) were determined by quantitative polymerase chain reaction (qPCR). The
      results indicate that the structures of bacterial and archaeal communities varied
      significantly with time and fertilization based on changes in the relative
      abundance of dominant T-RFs. The abundancy of the detected genes changed with
      time. The total bacteria, total archaea, and archaeal amoA were less abundant in
      July. The bacterial amoA and denitrifying genes were less abundant in September,
      except the nirK gene. The OF treatment increased the abundance of the observed
      genes, while the CF treatment had little influence on them. The soil temperature
      significantly affected the bacterial and archaeal community structures. The soil
      moisture was significantly correlated with the abundance of denitrifying genes.
      Of the soil chemical properties, soil organic carbon was the most important
      factor and was significantly correlated with the abundance of the detected genes,
      except the nirK gene. Overall, this study demonstrated the effects of both
      temporal alteration and organic fertilizer on the structures of microbial
      communities and the abundance of genes involved in the nitrogen cycle. 

PMID- 25367789
TI  - Designing a SCAR molecular marker for monitoring Trichoderma cf. harzianum in
      experimental communities.
AB  - Several species of the fungal genus Trichoderma establish biological interactions
      with various micro- and macro-organisms. Some of these interactions are relevant
      in ecological terms and in biotechnological applications, such as biocontrol,
      where Trichoderma could be considered as an invasive species that colonizes a
      recipient community. The success of this invasion depends on multiple factors,
      which can be assayed using experimental communities as study models. Therefore,
      the aim of this work is to develop a species-specific sequence-characterized
      amplified region (SCAR) marker to monitor the colonization and growth of T. cf.
      harzianum when it invades experimental communities. For this study, 16 randomly
      amplified polymorphic DNA (RAPD) primers of 10-mer were used to generate
      polymorphic patterns, one of which generated a band present only in strains of T.
      cf. harzianum. This band was cloned, sequenced, and five primers of 20-23 mer
      were designed. Primer pairs 2F2/2R2 and 2F2/2R3 successfully and specifically
      amplified fragments of 278 and 448 bp from the T. cf. harzianum BpT10a strain
      DNA, respectively. Both primer pairs were also tested against the DNA from 14
      strains of T. cf. harzianum and several strains of different fungal genera as
      specificity controls. Only the DNA from the strains of T. cf. harzianum was
      successfully amplified. Moreover, primer pair 2F2/2R2 was assessed by
      quantitative real-time polymerase chain reaction (PCR) using fungal DNA mixtures
      and DNA extracted from fungal experimental communities as templates. T. cf.
      harzianum was detectable even when as few as 100 copies of the SCAR marker were
      available or even when its population represented only 0.1% of the whole
      community. 

PMID- 25367790
TI  - Vitreoscilla hemoglobin promotes Salecan production by Agrobacterium sp. ZX09.
AB  - Salecan is a novel exopolysaccharide produced by the strain Agrobacterium sp.
      ZX09, and it is composed of only glucose monomers. The unique chemical
      composition and excellent physicochemical properties make Salecan a promising
      material for applications in coagulation, lubrication, protection against acute
      liver injury, and alleviating constipation. In this study, we cloned the
      Vitreoscilla hemoglobin gene into a broad-host-range plasmid pCM158. Without
      antibiotic selection, there was negligible loss of the plasmid in the host
      Agrobacterium sp. ZX09 after one passage of cultivation. The expression of
      Vitreoscilla hemoglobin was demonstrated by carbon monoxide (CO) difference
      spectrum. The engineered strain Agrobacterium sp. ZX09 increased Salecan yield by
      30%. The other physiological changes included its elevated respiration rate and
      cellular invertase activity. 

PMID- 25367791
TI  - Positional variation in grain mineral nutrients within a rice panicle and its
      relation to phytic acid concentration.
AB  - Six japonica rice genotypes, differing in panicle type, grain density, and phytic
      acid (PA) content, were applied to investigate the effect of grain position on
      the concentrations of major mineral nutrients and its relation to PA content and
      grain weight within a panicle. Grain position significantly affected the
      concentrations of the studied minerals in both the vertical and horizontal axes
      of a rice panicle. Heavy-weight grains, located on primary rachis and top rachis,
      generally had higher mineral concentrations, but were lower in PA concentration
      and molar ratios of PA/Zn, compared with the small-weight grains located on
      secondary rachis and bottom rachis, regardless of rice genotypes. However, on the
      basis of six rice genotypes, no significant correlations were found among mineral
      elements, PA, and grain weight. These results suggested that some desired
      minerals, like Zn and Fe, and their bioavailability, can be enhanced
      simultaneously by the modification of panicle patterns, and it will be helpful in
      the selection of rice genotypes with low PA and high mineral nutrients for
      further breeding strategy without sacrificing their high yields. 

PMID- 25367792
TI  - Development of 107 SSR markers from whole genome shotgun sequences of Chinese
      bayberry (Myrica rubra) and their application in seedling identification.
AB  - Chinese bayberry (Myrica rubra Sieb. et Zucc.) is one of the important
      subtropical fruit crops native to the South of China and Asian countries. In this
      study, 107 novel simple sequence repeat (SSR) molecular markers, a powerful tool
      for genetic diversity studies, cultivar identification, and linkage map
      construction, were developed and characterized from whole genome shotgun
      sequences. M13 tailing for forward primers was applied as a simple method in
      different situations. In total, 828 alleles across 45 accessions were detected,
      with an average of 8 alleles per locus. The number of effective alleles ranged
      from 1.22 to 10.41 with an average of 4.08. The polymorphic information content
      (PIC) varied from 0.13 to 0.89, with an average of 0.63. Moreover, these markers
      could also be amplified in their related species Myrica cerifera (syn. Morella
      cerifera) and Myrica adenophora. Seventy-eight SSR markers can be used to produce
      a genetic map of a cross between 'Biqi' and 'Dongkui'. A neighbor-joining (NJ)
      tree was constructed to assess the genetic relationships among accessions, and
      the elite accessions 'Y2010-70', 'Y2012-140', and 'Y2012-145', were characterized
      as potential new genotypes for cultivation. 

PMID- 25367793
TI  - A mutation of Aspergillus niger for hyper-production of citric acid from corn
      meal hydrolysate in a bioreactor.
AB  - The properties of the screened mutants for hyper-production of citric acid
      induced by carbon ((12)C(6+)) ion beams and X-ray irradiation were investigated
      in our current study. Among these mutants, mutant H4002 screened from (12)C(6+)
      ion irradiation had a higher yield of citric acid production than the parental
      strain in a 250-ml shaking flash. These expanded submerged experiments in a
      bioreactor were also carried out for mutant H4002. The results showed that (177.7
      196.0) g/L citric acid was accumulated by H4002 through exploiting corn meal
      hydrolysate (containing initial 200.0-235.7 g/L sugar) with the productivity of
      (2.96-3.27) g/(L?h). This was especially true when the initial sugar
      concentration was 210 g/L, and the best economical citric acid production reached
      (187.5+/-0.7) g/L with a productivity of 3.13 g/(L?h). It was observed that
      mutant H4002 can utilize low-cost corn meal as a feedstock to efficiently produce
      citric acid. These results imply that the H4002 strain has the industrial
      production potentiality for citric acid and offers strong competition for the
      citric acid industry. 

PMID- 25367795
TI  - Retraction note to: Characterization of cancer stem-like cells in the side
      population cells of human gastric cancer cell line MKN-45.
AB  - Retraction Note to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2013 Mar.;
      14(3):216-223. This article has been retracted at the authors' request, as it
      contains large portions of text and figures that have been previously published
      in the following article: Zhang, H., Xi, H., Cai, A., Xia, Q., Wang, X.X., Lu,
      C., Zhang, Y., Song, Z., Wang, H., Li, Q., Chen, L., Guo, Z., 2013. Not all side
      population cells contain cancer stem-like cells in human gastric cancer cell
      lines. Dig. Dis. Sci., 58(1):132-139. [doi:10.1007/s10620-012-2330-1]

PMID- 25367796
TI  - Bag5 protects neuronal cells from amyloid beta-induced cell death.
AB  - The pathological mechanism of Alzheimer's disease (AD) needs to be elucidated.
      The Bcl-2 associated athanogene 5 (Bag5) is an important member in the Bag
      family. However, the role of Bag5 in AD has not yet been elucidated. In this
      study, we found that expression of Bag5 is elevated in the brains of AD
      transgenic Tg2576 mice at both mRNA levels and proteins. In vitro experiments
      indicated that Abeta1-42 treatment led to the upregulation of Bag5 in a dose
      dependent manner. In addition, our results indicated that inhibition of Bag5
      using small RNA interferences exacerbated Abeta1-42-induced neurotoxicity. On one
      hand, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and
      lactate dehydrogenase (LDH) assay demonstrated that inhibition of Bag5
      exacerbated Abeta1-42-related cell death. On the other hand, silence of
      endogenous Bag5 promotes the generation of reactive oxygen species (ROS) and
      malondialdehyde (MDA) induced by Abeta1-42. Finally and importantly, it was shown
      that knockdown of Bag5 exacerbated Abeta1-42-induced apoptosis and caspase-3
      cleavage. These data suggest that induction of Bag5 might have a neuroprotective
      effect in AD. 

PMID- 25367797
TI  - Upregulation of nucleoside triphosphate diphosphohydrolase-1 and ecto-5'
      nucleotidase in rat hippocampus after repeated low-dose dexamethasone
      administration.
AB  - Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog
      with profound effects on energy metabolism, immune system, and hypothalamic
      pituitary-adrenal axis, is widely used therapeutically, its impact on the brain
      is poorly understood. The aim of the present study was to explore the effect of
      repeated low-dose DEX administration on the activity and expression of the
      ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP
      and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were
      ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5'
      nucleotidase (eN), whereas the effects were evaluated in two brain areas that
      show different sensitivity to glucocorticoid action, hippocampus, and cerebral
      cortex. In the hippocampus, but not in cerebral cortex, modest level of
      neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and
      upregulation of NTPDase1 and eN mRNA expression ensued under the influence of
      DEX. The observed pattern of ectonucleotidase activation, which creates tissue
      volume with enhanced capacity for adenosine formation, is the hallmark of the
      response after different insults to the brain. 

PMID- 25367799
TI  - A common disease but rare presentation: branchial cyst located on tonsil.

PMID- 25367798
TI  - Elite level rhythmic gymnasts have significantly more and stronger pain than
      peers of similar age: a prospective study.
AB  - PURPOSE: Rhythmic gymnastics (RG) unites aesthetic, ballet-like motion, and all
      aspects of gymnastics. To reach elite level, girls begin at early age the
      intensive training. To date it is unclear if such demanding training influences
      the incidence and intensity of painful overuse injuries. The purpose of this
      study is to analyze anatomical painful regions and pain intensity in elite level
      rhythmic gymnasts (elRG) and compare results with an age-matched control group
      (CG). METHODS: This prospective field study was carried out at the European
      Championship in RG 2013 (218 participating athletes, Vienna, Austria).
      Volunteering athletes were interviewed according to a preformed questionnaire. As
      CG secondary school pupils without any competitive sports experience were
      analyzed accordingly. RESULTS: Overall, 243 young females (144 elRG/66 % of all
      participants and 99 CG) were observed. ElRGs were significantly (s.) smaller,
      lighter, and had s. stronger pain (p < 0.001). A total of 72 % of athletes
      reported to have at least one painful body region compared with 52 % of CG (p <
      0.001). ElRG had nearly three times more serious injuries than the CG. In all 23
      % off all elRG reported to have had no access to professional medical care. ElRGs
      were s. more frequently (25 vs 9 %) affected at the lumbar spine and the ankle
      joint (17.4 vs 7 %). CONCLUSION: To our knowledge, this trial analyzes the
      largest cohort of elRG to date. Hence, it is clearly alluded that intensive
      training in RG is a significant factor causing more and stronger pain than in a
      CG.

PMID- 25367800
TI  - Red cell distribution width: a novel prognostic factor of pulmonary embolism?

PMID- 25367801
TI  - Morphological transitions under oxidative stress in response to metabolite
      formation in Aspergillus niger.
AB  - Oxidative stress is associated with metabolite formation in fungi. In contrast to
      an Aspergillus niger wild-type strain, a sclerotia-formation regulator ansclR
      deletion strain demonstrated increased susceptibility to oxidative stress and
      reduced transcription of the catalase gene, catB, while an ansclR overexpression
      strain showed enhanced resistance to oxidative stress and increased expression of
      catB. In addition, ansclR complementation strain expressed a wild-type level of
      catB. The ansclR overexpression strain also produced the same metabolites as the
      wild type strain treated with H2O2. Furthermore, LC-MS, NMR, and IR analyses
      showed that the main metabolite was a steroid analog. Our study adds new clues to
      oxidative stress-related factors and metabolite formation in A. niger. 

PMID- 25367802
TI  - Chemoenzymatic synthesis of 1,3-dioleoyl-2-palmitoylglycerol.
AB  - We report the synthesis of 1,3-dioleoyl-2-palmitoylglycerol (OPO) by a three-step
      method. Vinyl oleate was first synthesized by transvinylation between vinyl
      acetate and oleic acid. This was further reacted with glycerol at 35  degrees C
      for 8 h using 10% (w/v) Novozym 435 to synthesize 1,3-diolein. The 1,3-diolein
      content in the crude reaction mixture was 90.8% and was obtained at 82.3% (w/w)
      yield with 98.6% purity after purification. Finally, OPO was chemically
      synthesized by reacting purified 1,3-diolein with palmitic acid. 94.8% OPO was
      produced in the crude reaction mixture and the regiopurity of OPO after
      purification was 98.7% at 90.5% yield based on positional distribution analysis.
      This is an innovative approach for the synthesis of 1,3-diolein in a solvent-free
      system as an alternative to previously presented studies that applied solvent
      system.

PMID- 25367803
TI  - Culturing Drosophila melanogaster (S2) in a chemostat.
AB  - Insect cells are used for the expression of complex proteins in products such as
      vaccines and biopharmaceuticals. Physiology of a Drosophila melanogaster (lineage
      S2), transfected to stably express rabies virus glycoprotein (RVGP), was studied
      in batch culture and in a chemostat with serum-free medium. In batch mode, the
      system reached 3 * 10(7) cells mL(-1) with specific growth rate of 1.5 d(-1) with
      RVGP at 2.50 ug L(-1). When operated continuously, three well-defined steady
      states were achieved at dilution rates (D) of 0.8, 0.5 and 0.2 d(-1). The
      residual glucose and glutamine concentrations and the cell yields on glucose and
      glutamine decreased at lower D. High values of substrate consumption for
      maintenance may explain this variation in yields. The results indicated that
      glucose is not the limiting substrate of this process. 

PMID- 25367804
TI  - Parenting in 2 Worlds: pilot results from a culturally adapted parenting program
      for urban American Indians.
AB  - This study reports the implementation and feasibility of a culturally adapted
      parenting curriculum, Parenting in 2 Worlds (P2W), which we designed specifically
      for urban American Indian families by means of community-based participatory
      research and then pilot tested in three Arizona cities. Data come from matched
      pre- and post-test surveys completed in 2012 by 75 American Indian parents of
      adolescents aged 10-17 who participated in the pilot version of P2W. P2W is a 10
      workshop program administered twice a week for 5 weeks by trained American Indian
      community facilitators. Parents completed pre-test surveys during Workshop 1 and
      post-test surveys 5 weeks later during Workshop 10. Paired t tests assessed
      changes in parenting outcomes, cultural identity, and child anti-social behavior.
      Changes from pre- to post-test demonstrated statistically significant
      improvements in several parenting outcomes (discipline, involvement, self-agency,
      and supervision), a strengthened sense of ethnic and cultural identity and Native
      spirituality, and a decrease in the child's anti-social behavior. These results,
      which show significant preliminary improvements in parenting skills and family
      functioning, suggest the feasibility of implementing a culturally grounded
      parenting intervention for urban American Indian parents.

PMID- 25367805
TI  - Association between contraband tobacco and illicit drug use among high school
      students in Canada.
AB  - A particularly challenging issue to tobacco cessation efforts is the availability
      of contraband cigarettes. While studies have linked contraband tobacco to smoking
      initiation and poor cessation outcomes, little is known about its association
      with illicit drug use among adolescents. We examine the association between
      contraband tobacco and illicit drug use among adolescent students using a
      national representative sample of 2,136 current smoker students in grades 9-12
      from the 2010-2011 Youth Smoking Survey. About 31 % of adolescent current smokers
      in grades 9-12 use contraband cigarettes. Prevalence in the use of illicit drugs
      ranged from 9 to 37 %, with MDMA being the most commonly used drug. Adjusted
      logistic regression revealed that smokers of contraband cigarettes, when compared
      with non-contraband cigarette smokers, were more likely to use cocaine (OR 2.14;
      CI 1.29-3.56), heroin (OR 7.92; CI 3.00-20.91), amphetamines (OR 4.25; CI 2.07
      8.74), MDMA (OR 2.00; CI 1.25-3.19), hallucinogens (OR 2.18; CI 1.34-3.55), and
      ketamine (OR 3.48; CI 1.61-7.54). This paper adds to the existing evidence of the
      negative effects of contraband tobacco by showing that adolescent contraband
      smokers are more likely to use illicit drugs. Given the addictive nature of these
      drugs and the potential for such behavior to spill over into adulthood, more
      efforts should be invested in addressing this problem.

PMID- 25367806
TI  - N-methyl-D-aspartate preconditioning prevents quinolinic acid-induced
      deregulation of glutamate and calcium homeostasis in mice hippocampus.
AB  - The search for new therapeutic strategies through modulation of glutamatergic
      transmission using effective neuroprotective agents is essential. Glutamatergic
      excitotoxicity is a major factor common to neurodegenerative diseases and in
      acute events such as cerebral ischemia, traumatic brain injury and epilepsy. We
      have previously demonstrated that N-methyl-D-aspartate (NMDA) preconditioning in
      mice showed 50 % of protection against seizures and full protection against
      damage to neuronal tissue induced by quinolinic acid (QA). In this study,
      cellular and molecular mechanisms involved on NMDA preconditioning and
      neuroprotection were investigated in mice treated with NMDA 24 h before QA
      insult. Calcium uptake and D-aspartate release from hippocampal slices obtained
      from mice treated with NMDA plus QA and not displaying seizures (protected mice)
      were similar to control (saline) or NMDA preconditioned mice. Increased calcium
      uptake and glutamate release is evidenced in unprotected (convulsed) mice as well
      as QA control, demonstrating that calcium and glutamate are involved in NMDA
      induced preconditioning. Increased glutamate release evoked by QA was blocked by
      MK-801, whereas increased calcium uptake was abolished by voltage-dependent
      calcium channels inhibitors, but not MK-801. NMDA preconditioning is effective in
      normalizing the deregulation of glutamate transport and calcium homeostasis
      evoked by QA due to aberrant NMDA receptors activation that culminates in
      seizures and hippocampal cells damage. 

PMID- 25367808
TI  - Therapeutic results of abdominoperineal resection in the prone jackknife position
      for T3-4 low rectal cancers.
AB  - OBJECTIVE: To evaluate the therapeutic results of abdominoperineal resections in
      the prone jackknife position for T3-4 low rectal cancers. METHODS: From January
      2002 to January 2011, 536 patients with T3-T4 low rectal cancer underwent
      abdominoperineal resection. Two hundred forty-three were treated in the Lloyd
      Davies position and 293 in the prone jackknife position. Clinicopathological data
      and survival of the two groups were analyzed retrospectively. RESULTS:
      Abdominoperineal resections in the prone jackknife position group were associated
      with significantly less blood loss (124 +/- 50.68 vs 210.67 +/- 83.32 ml, P <
      0.001) and shorter operation times (3.10 +/- 1.08 vs 3.82 +/- 1.43 h, p = 0.010)
      than those in Lloyd-Davies position group. The total local recurrence rate is 8.4
      % (45/536). The local recurrence rate in the prone jackknife position group was
      significantly lower than in the Lloyd-Davies position group (5.5 vs 11.9 %, P <
      0.001). By multivariate regression analysis, depth of tumor invasion (P = 0.032),
      CRM (P < 0.001), and position (P = 0.015) were found to be independent risk
      factors for local recurrence. Multivariate Cox regression survival analysis,
      lymph node metastasis, and CRM (P < 0.001) were proven to be the major
      independent prognostic factors for T3-T4 low rectal cancer patients. CONCLUSIONS:
      Abdominoperineal resection in the prone jackknife position for T3-T4 low rectal
      cancers is feasible and has a lower local recurrence.

PMID- 25367807
TI  - Enhanced aggressive behaviour in a mouse model of depression.
AB  - Depression is one of the most common chronic mental disorders, which is a leading
      cause of morbidity and mortality in patients. Depression often leads to offensive
      and defensive behaviours but the underlying mechanisms are not known. We propose
      that the aggressive behaviours in depression can be modelled in animal
      experiments. In this study, we successfully established a mouse model of
      depression using the chronic unpredictable mild stress (CUMS) paradigm and
      detected aggressive and social dominance behaviours in rodents by
      resident/intruder test and social dominance tube test (SDTT), respectively. The
      CUMS-exposed mice showed increased defensive, offensive and aggressive behaviours
      in the resident-intruder test. In the SDTT, these mice showed enhanced social
      dominance. These alterations were associated with reduced MAP-2 expression in the
      hippocampus while no difference in beta-tubulin expression was detected. In
      addition, the treatment of anti-depressant fluoxetine reversed the aggressive
      behaviours without reducing the social dominance behaviour induced by CUMS.
      However, fluoxetine did effectively reverted the changes in MAP-2 expression in
      the hippocampus. In addition, the nonspecific tricyclic antipsychotic drug,
      clozapine, reversed all symptoms of CUMS-exposed mice including aggressive
      tendencies, impulsive violence, social dominance behaviour and MAP-2 expression
      in the hippocampus. The results suggests that social maladjustment such as
      competition and social dominance are likely related to the dopaminergic system
      rather than the serotonergic system and the hippocampal dendritic structure
      protein MAP-2. Thus, dominance can be separated from aggression. This study shows
      that aggression/hostility and social hierarchy/dominance are increased in the
      CUMS-exposed mice and thus provide an excellent model for further study in the
      diagnosis and the treatment of depression-associated aggression. 

PMID- 25367809
TI  - Position of Edwards SAPIEN transcatheter valve in the aortic root in relation
      with the coronary ostia: implications for percutaneous coronary interventions.
AB  - OBJECTIVES: To determine the implications of stable coverage of the coronary
      ostia by the Edwards SAPIEN valve frame in terms of myocardial ischemia and
      subsequent percutaneous coronary intervention (PCI), following transcatheter
      aortic valve implantation (TAVI). BACKGROUND: Edwards SAPIEN frame is frequently
      deployed relatively higher than recommended and may overlap the coronary ostia.
      METHODS: A total of 142 patients (age 81 +/- 7 years, male 49%) treated with
      Edwards SAPIEN valve and with multi-detector row computed tomography at 1 month
      follow-up were evaluated. The position of the frame in relation to the coronary
      ostia was assessed. Levels of troponin T were measured 12-24 hr after TAVI. PCI
      events at follow-up were recorded. RESULTS: The left coronary ostium was fully
      covered in three (2.1%) patients and the right coronary ostium in 11 (7.7%).
      There were no differences in troponin T levels between patients with fully
      covered ostia versus patients with partly or non-covered ostia (0.24 (0.13-0.50)
      MUg/L versus 0.35 (0.15-0.55) MUg/L, respectively; P = 0.377). At 30 +/- 15
      months follow up, 10 (7%) patients underwent successful PCI. Rate of subsequent
      PCI was similar between patients with any covered ostium and patients with non
      covered ostia [4 (7.8%) vs. 6 (6.5%), P = 0.780, respectively]. CONCLUSIONS: Full
      overlap of the coronary ostia by Edwards SAPIEN frame is infrequent and in most
      cases does not limit subsequent PCI.

PMID- 25367810
TI  - Comparison of re-biopsy with preceded MRI and re-biopsy without preceded MRI in
      patients with previous negative biopsy and persistently high PSA.
AB  - PURPOSE: To retrospectively compare re-biopsy with preceded magnetic resonance
      imaging (MRI) and re-biopsy without preceded MRI. MATERIALS AND METHODS: Between
      January 2007 and May 2011, 669 patients (mean 64 years; range 38-91 years)
      underwent a re-biopsy because of previous negative biopsy (median 1; 1-5) and
      persistently high prostate-specific antigen (PSA 10.6 ng/ml; 2.5-997.1 ng/ml). 3T
      MRI using a phased-array coil was performed in 171 (MRI group) but not in 498
      (non-MRI group) prior to re-biopsy. Transrectal ultrasound-guided biopsy was
      performed in both MRI and non-MRI groups. MRI and non-MRI groups were compared in
      terms of cancer detection rate [(number of cancer-proven patients/number of
      patients in MRI or non-MRI group) * 100] and positive core rate [(number of
      cancer-positive cores/number of cores in MRI or non-MRI group) * 100] using
      Fisher exact test. Odds ratio and 95% confidence interval were also obtained.
      Pathologic diagnosis of the biopsy was considered standard reference. RESULTS: Of
      669 patients, 129 (19.3%) were diagnosed with adenocarcinoma. The cancer
      detection rates of MRI and non-MRI groups were 33.3% (57/171) and 14.5% (72/498),
      respectively (p < 0.001). The positive core rates of these groups were 9.2%
      (167/1 818) and 3.2% (179/5 631), respectively (p < 0.001). The odd ratios of
      cancer detection rate and positive core rate were 3.0 (95% confidence interval
      2.0-4.4) and 3.1 (2.5-3.8), respectively. CONCLUSION: Re-biopsy with preceded MRI
      yields higher cancer detection rate and positive core rate than re-biopsy without
      preceded MRI. MRI should be considered prior to re-biopsy in patients with
      previous negative biopsy and persistently high PSA.

PMID- 25367811
TI  - The comb sign.

PMID- 25367812
TI  - The "pancake" adrenal.
AB  - The pancake has been used as the metaphorical description for the abnormal
      appearance of the adrenal gland when the ipsilateral kidney is absent from the
      renal fossa. Once detected, the abnormal adrenal appearance should prompt a
      careful survey of the patient to exclude renal agenesis or discover the ectopic
      kidney, conditions often associated with other congenital anomalies. 

PMID- 25367813
TI  - Correlation analysis of computed tomography imaging score with the presence of
      acute kidney injury in severe acute pancreatitis.
AB  - OBJECTIVES: The aim of the study is to investigate the CT imaging findings of
      severe acute pancreatitis (SAP) complicated with acute kidney injury (AKI) and
      evaluate the correlation between the CT imaging score and the presence of AKI in
      SAP. MATERIALS AND METHODS: Contrast-enhanced CT scanning was performed for all
      145 patients. Related CT indices such as Balthazar CT grading, CTSI and EPIC
      scores were calculated. Clinical data, including APACHE II, Ranson scores, serum
      creatinine levels, urine output, and mortality, were then collected and compared
      with CT indices. RESULTS: The EPIC score showed a larger area under the receiver
      operating characteristic curve than either of the CTSI or Balthazar score.
      However, the change of APACHE II score, but not EPIC score, was significantly
      associated with the prognosis of AKI and eventual clinical outcome. In addition,
      the CT manifestation of fluid encapsulation was a good predictor of recovery from
      AKI. CONCLUSIONS: Among the CT indices, the EPIC score, which possessed a good
      correlation with both APACHE II and Ranson scores, provided a better prediction
      of AKI in SAP patients than CTSI and Balthazar scores. Encapsulation of
      inflammatory exudates might be used in the future as imaging-based prognostic
      criteria of recovering from AKI in patients with SAP.

PMID- 25367814
TI  - Effect of needle gauge and lobe laterality on parenchymal liver biopsy outcome: a
      retrospective analysis.
AB  - PURPOSE: To analyze the effect of lobe selection, needle gauge, and number of
      passes on procedure outcomes in terms of specimen length and post-procedure
      complications. METHODS: In this HIPAA-compliant, IRB-approved retrospective
      study, the data from 771 ultrasound-guided adult parenchymal liver biopsies were
      analyzed. Post-procedure complications were assigned a 3-point rating scale.
      Associations between specimen length and post-procedure complications with lobe
      laterality, needle gauge, and number of passes were analyzed. Multivariate
      logistic regression models were used to analyze the likelihood for achieving a
      specimen length of at least 2 cm. RESULTS: Post-procedure complications were not
      associated with lobe laterality, needle gauge, and number of passes (p > 0.3).
      Specimen length was associated with the number of passes dichotomized at the
      study mean (p = 0.007), but not with lobe laterality or needle gauge (p > 0.2).
      After adjusting for lobe laterality and needle gauge, procedures with 1 or 2
      passes were associated with a higher likelihood of obtaining a 2 cm or longer
      specimen (OR 2.469; CI 1.08-5.63, p = 0.0315) than procedures with 3 or more
      passes, possibly due to poorer sample quality. After adjusting for lobe
      laterality, an 18-gauge needle was associated with higher odds of a biopsy
      procedure with 1 or 2 passes (OR 3.665; CI 1.93-6.95, p < 0.0001) than a 20-gauge
      needle. CONCLUSIONS: Lobe laterality was not associated with specimen length or
      post-procedure complications. An 18-gauge needle compared to a 20-gauge needle
      could reduce the need for a procedure with more than 2 passes. There was no
      difference in post-procedure complications between the two needle sizes.

PMID- 25367815
TI  - Serum cystatin C is not an appropriate marker for kidney involvement in patients
      with primary Sjogren's syndrome.
AB  - OBJECTIVES: We aimed to investigate serum cystatin C (cysC) levels in primary
      Sjogren's syndrome (pSS) patients, and evaluate its correlation with renal
      involment. MATERIALS AND METHODS: Eighty-six pSS patients and 65 age- and gender
      matched healthy controls were enrolled into the study. Serum cysC, urea, serum
      creatinine (SCr), creatinine clearance (CrCl), glomerular filtration rates (GFR),
      Na, K, Mg, Ca, uric acid, P, erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), anti-Ro/SS-A, anti-La/SS-B, antinuclear antibodies, 24-h urinary
      poteinuria and microalbuminuria were evaluated. RESULTS: Mean serum cysC levels
      did not differ between the patients and healthy controls (P > 0.05). Nine
      patients with pSS had proteinuria over 150 mg (and microalbuminuria over 30 mg)
      per 24 h. In patients with proteinuria, serum cysC levels correlated with serum K
      (r = 0.279, P = 0.024), ESR (r = 0.405, P = 0.001) and the disease duration (r =
      0.235, P = 0.04), respectively. Patients with positive anti-Ro/SS-A and anti
      La/SS-B antibodies had higher SCr levels compared to those with negative serology
      (r = 0.292, P = 0.009, and r = 0.259, P = 0.022, respectively). Nine patients
      with proteinuria and anti-Ro/SS-A, anti-La/SS-B positivity tended to have lower K
      and Mg levels which suggests subclinical renal tubular acidosis. CONCLUSION:
      There were no associations between serum cysC levels and renal involvement in
      patients with pSS. However, in patients with proteinuria, serum cysC levels were
      correlated with acute-phase reactants, suggesting an association with disease
      activity in terms of degree of inflammation.

PMID- 25367816
TI  - The Affordable Care Act: a case study for understanding and applying complexity
      concepts to health care reform.
AB  - RATIONALE, AIMS AND OBJECTIVES: The current health system in the United States is
      the result of a history of patchwork policy decisions and cultural assumptions
      that have led to persistent contradictions in practice, gaps in coverage,
      unsustainable costs, and inconsistent outcomes. In working toward a more
      efficient health system, understanding and applying complexity science concepts
      will allow for policy that better promotes desired outcomes and minimizes the
      effects of unintended consequences. METHODS: This paper will consider three
      applied complexity science concepts in the context of the Patient Protection and
      Affordable Care Act (PPACA): developing a shared vision around reimbursement for
      value, creating an environment for emergence through simple rules, and embracing
      transformational leadership at all levels. RESULTS AND CONCLUSIONS: Transforming
      the US health system, or any other health system, will be neither easy nor quick.
      Applying complexity concepts to health reform efforts, however, will facilitate
      long-term change in all levels, leading to health systems that are more
      effective, efficient, and equitable.

PMID- 25367817
TI  - Antitumor properties of a new non-anticoagulant heparin analog from the mollusk
      Nodipecten nodosus: Effect on P-selectin, heparanase, metastasis and cellular
      recruitment.
AB  - Inflammation and cancer are related pathologies acting synergistically to promote
      tumor progression. In both, hematogenous metastasis and inflammation, P-selectin
      participates in interactions involving tumor cells, platelets, leukocytes and
      endothelium. Heparin has been shown to inhibit P-selectin and as a consequence it
      blunts metastasis and inflammation. Some heparin analogs obtained from marine
      invertebrates are P-selectin inhibitors and do not induce bleeding effects. The
      present work focuses on the P-selectin blocking activity of a unique heparan
      sulfate (HS) from the bivalve mollusk Nodipecten nodosus. Initially, we showed
      that the mollusk HS inhibited LS180 colon carcinoma cell adhesion to immobilized
      P-selectin in a dose-dependent manner. In addition, we demonstrated that this
      glycan attenuates leukocyte rolling on activated endothelium and inflammatory
      cell recruitment in thioglycollate-induced peritonitis in mice. Biochemical
      analysis indicated that the invertebrate glycan also inhibits heparanase, a key
      player in cell invasion and metastasis. Experimental metastasis of Lewis lung
      carcinoma cells was drastically attenuated by the mollusk HS through a mechanism
      involving inhibition of platelet-tumor-cell complex formation in blood vessels.
      These data suggest that the mollusk HS is a potential alternative to heparin for
      inhibiting P-selectin-mediated events such as metastasis and inflammatory cell
      recruitment. 

PMID- 25367818
TI  - Trends in self-reported sleep problems, tiredness and related school performance
      among Finnish adolescents from 1984 to 2011.
AB  - The aim of this study was to investigate long-term trends in insomnia symptoms,
      tiredness and school performance among Finnish adolescents. A time-series from
      1984 to 2011 was analysed from two large-scale survey studies, the Finnish School
      Health Promotion Study and the Health Behavior in School-Aged Children study. A
      total of 1,136,583 adolescents aged 11-18 years answered a standardized
      questionnaire assessing frequency of insomnia symptoms, tiredness and school
      performance. A clear approximately twofold increasing trend in insomnia symptoms
      and tiredness was found from the mid-1990s to the end of the 2000s. The increase
      was evident in all participating age groups and in both genders. After 2008, the
      increase seems to have stopped. Insomnia symptoms and tiredness were associated
      with lower school performance and they were more prevalent among girls (11.9 and
      18.4%) compared to boys (6.9 and 9.0%, respectively). Unexpectedly, we also
      observed an increasingly widening gap in school performance between normally
      vigilant and chronically tired pupils. The underlying causes of these phenomena
      are unknown, but may concern changes in the broader society. The observed recent
      increasing trend in adolescents' sleep problems is worrisome: poor sleep quality
      has also been suggested to associate with clinical or subclinical mood or anxiety
      disorders and behavioural problems and predispose to sleep and psychiatric
      disorders later in life. Our results justify further studies and call for serious
      attention to be paid to adolescent's sleep in the Finnish educational system and
      society at large.

PMID- 25367819
TI  - Development and validation of a scale measuring the locus of control orientation
      in relation to socio-dental effects.
AB  - AIM: To develop a socio-dental impact locus of control scale (SILOC) and to study
      its relationship with oral health status as well as dental attendance. STUDY
      DESIGN: Observational cross-sectional study design. METHOD: A seven-item SILOC
      scale based on locus of control and the WHO international classification of
      diseases' criteria for "Disability" in relation to oral health was developed. In
      the pilot study, 100 adolescent school children returned completed forms
      containing the multidimensional health locus of control (MHLC) and the (SILOC)
      scale. After confirmation of reliability and validity, 509 adolescent school
      children returned completed SILOC questionnaires and were examined for caries,
      plaque and gingivitis. A history of postponement of needed dental treatment was
      also elicited. RESULTS: The SILOC scores were highly correlated with the MHLC
      scores. Factor analysis revealed a two-factor solution accounting for 59 % of the
      variance. A Cronbach's alpha of 0.75 showed its internal consistency. Those with
      higher SILOC scores had greater levels of caries, plaque, gingivitis, and a
      history of postponing needed dental visits. Multiple logistic regression analysis
      after adjusting for potential confounders showed that those with high SILOC
      scores were more likely to have caries (OR = 3.32, p < 0.001), plaque (OR = 1.83,
      p = 0.026), gingivitis (OR = 1.80, p = 0.012) and a history of 'Postponement of
      needed dental treatment' (OR = 4.5, p < 0.001) as compared with the others.
      CONCLUSIONS: The SILOC scale showed satisfactory reliability and validity in
      measuring locus of control orientation in an Indian adolescent population.

PMID- 25367820
TI  - Knowledge and behaviour of parents in relation to the oral and dental health of
      children aged 4-6 years.
AB  - AIM: To evaluate baseline knowledge and behaviour of parents with regard to the
      oral and dental health of their young children. METHODS: Following ethical
      approval, six urban and rural schools were identified. Questionnaires were
      distributed to the parents of pupils (children aged 4-6 years). The questionnaire
      included several questions evaluating parental knowledge and behaviour of oral
      and dental health issues in their children. Each question was assigned a score of
      either 0 or 1 being inconsistent or consistent with current paediatric guidelines
      giving a maximum score of 6 for knowledge and 7 for behaviour. Chi-square
      analysis was used to analyse associations among variables. RESULTS: Parental
      knowledge varied widely among parents and across questions; however, 70.2 % of
      parents had scores greater than 3 (range 0-6). The majority of parents (65.8 %)
      also had scores greater than 3 (range 0-7) for behaviour. Deficiencies were noted
      in oral hygiene practices; very few parents brushed their child's teeth and were
      not aware of the recommended age of the first dental visit at 1 year (Age 1
      visit). Parents without free medical care demonstrated high levels of knowledge
      (P < 0.05). Almost half of the parents thought that the information available to
      them on the oral health of their young children was insufficient. CONCLUSION:
      Parents appeared to have limited knowledge regarding the dental and oral health
      of their young children. This study indicates a need for improved education for
      parents, particularly in toothbrushing behaviour and use of toothpaste. Education
      strategies tailored to the Irish population should be explored.

PMID- 25367821
TI  - Unique solution to the difficult problem of an aorto-duodenal fistula in a
      regional centre.

PMID- 25367822
TI  - Systematic review of the electrocardiographic changes in the takotsubo syndrome.

PMID- 25367823
TI  - Intervention during pregnancy to reduce excessive gestational weight gain-a
      randomised controlled trial.
AB  - OBJECTIVE: To evaluate if a feasible, low-cost intervention could decrease the
      percentage of women gaining weight above the Institute of Medicine (IOM)
      recommendations on gestational weight gain (GWG) compared with standard maternity
      care. DESIGN: A randomised controlled interventional design. SETTING: Antenatal
      clinics (n = 14) in Orebro county, Sweden, participated. POPULATION: Healthy
      women with a body mass index (BMI) >=19 kg/m(2), age >=18 years and adequate
      knowledge of Swedish language who signed in for maternity care at <=16 weeks of
      gestation. METHODS: Standard care was compared with a composite intervention
      consisting of education on recommended GWG according to IOM, application of
      personalised weight graph, formalised prescription of exercise and regular
      monitoring of GWG at every antenatal visit. OUTCOME: The proportion of women
      gaining weight above IOM guidelines (1990) and mean GWG (kg) was compared between
      groups. RESULTS: In all, 445 women were randomised and 374 women remained for
      analysis after delivery. A majority of the women analysed were normal weight
      (72%). The intervention reduced the proportion of women who exceeded the IOM
      guidelines (41.1% versus 50.0%). The reduction was, however, not statistically
      significant (P = 0.086). Mean GWG was significantly lower among women receiving
      the intervention, 14.2 kg (SD 4.4) versus 15.3 kg (SD 5.4) in the standard care
      group (P = 0.029). CONCLUSIONS: The low-cost intervention programme tested did
      significantly reduce the mean GWG but the proportion of women who exceeded the
      IOM recommendations for GWG was not significantly lower. ClinicalTrials.gov Id
      NCT00451425 http://clinicaltrials.gov.

PMID- 25367824
TI  - Integrating novel chemical weapons and evolutionarily increased competitive
      ability in success of a tropical invader.
AB  - The evolution of increased competitive ability (EICA) hypothesis and the novel
      weapons hypothesis (NWH) are two non-mutually exclusive mechanisms for exotic
      plant invasions, but few studies have simultaneously tested these hypotheses.
      Here we aimed to integrate them in the context of Chromolaena odorata invasion.
      We conducted two common garden experiments in order to test the EICA hypothesis,
      and two laboratory experiments in order to test the NWH. In common conditions, C.
      odorata plants from the nonnative range were better competitors but not larger
      than plants from the native range, either with or without the experimental
      manipulation of consumers. Chromolaena odorata plants from the nonnative range
      were more poorly defended against aboveground herbivores but better defended
      against soil-borne enemies. Chromolaena odorata plants from the nonnative range
      produced more odoratin (Eupatorium) (a unique compound of C. odorata with both
      allelopathic and defensive activities) and elicited stronger allelopathic effects
      on species native to China, the nonnative range of the invader, than on natives
      of Mexico, the native range of the invader. Our results suggest that invasive
      plants may evolve increased competitive ability after being introduced by
      increasing the production of novel allelochemicals, potentially in response to
      naive competitors and new enemy regimes. 

PMID- 25367825
TI  - Review article: selective histone deacetylase isoforms as potential therapeutic
      targets in inflammatory bowel diseases.
AB  - BACKGROUND: A link between histone deacetylases (HDACs) and intestinal
      inflammation has been established. HDAC inhibitors that target gut-selective
      inflammatory pathways represent a potential new therapeutic strategy in patients
      with refractory inflammatory bowel diseases (IBD). AIMS: To review the use of
      selective HDAC inhibitors to treat gut inflammation and to highlight potential
      improvements in selectivity/sensitivity by additional targeting of HDAC
      regulating microRNAs (miRNAs). METHODS: Original articles and reviews have been
      identified using PubMed search terms: 'histone deacetylase', 'HDAC inhibitor',
      'inflammatory bowel disease', 'gut inflammation,' and 'microRNA and HDAC'.
      RESULTS: The use of butyrate in distal colitis provided the first evidence that
      inhibition of HDACs decreases intestinal inflammation in IBD. HDAC inhibitors,
      such as valproic acid, vorinostat and givinostat, reduce inflammation and tissue
      damage in experimental murine colitis. Potential mechanisms of action for HDAC
      inhibitors include increased apoptosis, reduction of pro-inflammatory cytokine
      release, regulation of transcription factors and modulation of HDAC-regulatory
      miRNAs. HDAC2, HDAC3, HDAC6, HDAC9 and HDAC10 isoforms seem to be specifically
      involved in chronic intestinal inflammation, justifying the use of selective
      inhibitors as new therapeutic strategies in IBD. Controlling miRNAs for these
      isoforms can be identified. CONCLUSIONS: The pro-inflammatory influence of HDACs
      in the gut has been confirmed, but mostly in murine studies. Considerably more
      human data are required to permit development of selective HDAC inhibitors for
      IBD treatment. Inhibition of key HDAC isoforms in combination with modulation of
      HDAC-regulatory miRNAs has potential as a novel therapeutic approach.

PMID- 25367826
TI  - Children with Atopic Dermatitis Should Always be Patch-tested if They Have Hand
      or Foot Dermatitis.
AB  - Atopic dermatitis is the most common chronic inflammatory disease among children
      in industrialised countries. Many factors influence this disease in a negative
      way and contact allergy is one such factor. The aim of the study was to examine
      the frequency of contact allergy among children with the diagnosis atopic
      dermatitis. Contact allergy was found in 22/82 children (26.8%), the most common
      from Amerchol L101 (11.0%), potassium dichromate (7.3%), and nickel sulfate
      (4.9%). A statistically significant difference in contact allergy frequency was
      demonstrated for those with hand and/or foot eczema compared to those without.
      Children with atopic dermatitis who suffer from hand and/or foot dermatitis
      should always be patch-tested to evaluate whether they have a relevant contact
      allergy and thus allergic contact dermatitis.

PMID- 25367827
TI  - Sigmoid volvulus treated by mini-incision.
AB  - Definitive surgical management of sigmoid volvulus is usually via a midline
      laparotomy or laparoscopy. We report our experience with a series of five
      consecutive cases over a 10-year period. All patients had definitive surgery via
      a left iliac fossa mini-incision after prior decompression. For four patients, it
      was the first episode of sigmoid volvulus and one patient had a recurrent sigmoid
      volvulus after previous sigmoid colectomy. The latter patient had pan colonic
      megacolon diagnosed at initial surgery. All five cases were surgically treated
      successfully via a mini-incision on the left iliac fossa. There were no instances
      of recurrence at a median follow-up duration of 95 months (range 7-132 months). A
      left iliac fossa mini-incision is sufficient for the definitive management of non
      perforated sigmoid volvulus. Larger studies are warranted to draw definitive
      conclusions.

PMID- 25367828
TI  - Staying on target.

PMID- 25367829
TI  - Synthesis of novel symmetrical 2-oxo-spiro[indole-3,4'-pyridines] by a reaction
      of oxindoles with 1,2-diaza-1,3-dienes.
AB  - A simple reaction of some oxindole derivatives with 1,2-diaza-1,3-dienes to
      produce 2-oxo-spiro[indole-3,4'-pyridines] in good yields is described here. This
      transformation represents a practical two steps approach to new and biologically
      interesting 2-oxo-spiro[indole-3,4'-pyridine] scaffolds using a double Michael
      addition/cyclization sequence. 

PMID- 25367830
TI  - Macular retinal detachment associated with intrachoroidal cavitation in myopic
      patients.
AB  - PURPOSE: To investigate the clinical characteristics and treatment outcomes of
      macular retinal detachment (MRD) associated with intrachoroidal cavitation (ICC)
      in myopic patients. METHODS: In this retrospective, consecutive, interventional
      case series, five patients with ICC and associated MRD were enrolled from January
      2005 to December 2012. Basic ocular characteristics and clinical appearances of
      their ICC and MRD were recorded. Individual treatment courses were assessed with
      fundus photographs and serial optical coherence tomography. RESULTS: The average
      age and refraction were 43.8 +/- 11.0 years old and -9.37 +/- 2.73 diopters,
      respectively. Initial BCVA ranged from 20/100 to 20/30. Definite communication
      between the ICC and the subretinal space was noted in one case, suspected
      curvilinear communication in two cases, and between the peripapillary area and
      the subretinal space in two cases. Two cases received intravitreal injection of
      perfluoropropane and peripapillary laser; subretinal fluid (SRF) resolved in one
      and decreased in the other. One case had SRF reabsorbed after prolonged use of
      topical carbonic anhydrase inhibitor. CONCLUSIONS: ICC in high myopic patients
      may be associated with MRD. There might be communication between the ICC and the
      subretinal space. Intravitreal injection of an expansile gas may be beneficial,
      but the best treatment remains undetermined.

PMID- 25367831
TI  - Sutureless scleral fixation of intraocular lenses: outcomes of two approaches.
      The 2014 Yasuo Tano Memorial Lecture.
AB  - PURPOSE: We sought to assess the clinical outcomes and complications of two
      approaches to scleral fixation of intraocular lenses (IOLs): transconjunctival
      fixation through trocar cannulas and fixation using scleral tunnels created with
      a microvitreoretinal (MVR) blade. METHODS: This retrospective chart review was
      comprised of 23 eyes that received scleral fixation of a three-piece IOL with
      concurrent pars plana vitrectomy between June 2012 and June 2014. Scleral
      fixation was performed either by transconjunctival fixation through trocar
      cannulas (cannula fixation) or by the creation of scleral tunnels using an MVR
      blade (tunnel fixation). The preoperative and postoperative corrected distance
      visual acuities (CDVA), spherical equivalents (SE), and complications were
      evaluated. RESULTS: 15 cannula fixations and 8 tunnel fixations were performed.
      Mean follow-up was 353 days (Range: 94 - 790 days). Fifteen IOLs were fixated 2
      mm posterior to the limbus. Seven IOLs were fixated 1.5 mm posterior to the
      limbus, and one IOL was fixated 0.75 mm posterior to the limbus. Mean
      preoperative CDVA was logMAR 1.17 (Snellen 20/297), and mean postoperative CDVA
      was logMAR 0.37 (Snellen 20/47) (p <0.0001). At last follow-up, none of the IOLs
      have dislocated or subluxed and there has been no erosion of the subconjunctival
      haptics. CONCLUSIONS: Scleral fixation of IOLs using trocar cannulas or scleral
      tunnels is an effective surgical option for the treatment of aphakia or IOL
      dislocation. Both techniques result in significant visual improvement with
      minimal postoperative complications.

PMID- 25367832
TI  - The accuracy of home monitoring to detect disease activity during maintenance
      therapy for neovascular ARMD.
AB  - PURPOSE: To report the reproducibility, sensitivity, specificity, and predictive
      value of home monitoring for disease activity in neovascular age-related macular
      degeneration (ARMD). METHODS: Participants were trained to complete three
      separate home monitoring tasks, designed to identify subtle changes in visual
      function that may indicate increasing neovascular ARMD disease activity. These
      included measurement of near acuity and assessments of environmental distortion
      and overall visual function. The need for repeat intra-vitreal injection, as
      predicted by home monitoring, was compared to standard clinical assessment
      involving ETDRS distance acuity, slit lamp examination, and spectral domain
      ocular coherence tomography. RESULTS: Although all participants were able to
      complete the home monitoring tasks, the reproducibility of each of the three
      tasks was modest. Cohen's kappa was 0.118 (p = 0.54) for the comparison of the
      outcome of the home monitoring exercise with the gold standard of hospital
      assessment to determine disease activity. The sensitivity of the home monitoring
      exercise was 33.3 % (95 % CI 15.2-51.4) and the specificity was 77.8 % (95 % CI
      61.8-93.8). CONCLUSIONS: This study suggests that current tests of visual
      function, which are readily completed at home, cannot replace traditional clinic
      based assessments for neovascular ARMD disease activity. Instead, such tests are
      likely to remain complementary to standard assessment in clinic.

PMID- 25367833
TI  - Correlation between serum level of vascular endothelial growth factor and
      subfoveal choroidal thickness in patients with POEMS syndrome.
AB  - PURPOSE: The study was conducted to determine whether serum vascular endothelial
      growth factor (VEGF) levels are significantly correlated with subfoveal choroidal
      thickness (CT) and foveal thickness (FT) in patients with polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS)
      syndrome. PATIENTS AND METHODS: In this cross-sectional observational case
      series, we studied 31 eyes of 16 treatment-naive patients with POEMS syndrome
      with no evidence of fundus abnormalities. Subfoveal CT and FT were measured using
      enhanced depth imaging optical coherence tomography (EDI-OCT), and correlations
      between serum VEGF levels and subfoveal CT and FT were determined. RESULTS: The
      mean subfoveal CT was 417.9 +/- 73.5 MUm (right eye, 416.7 +/- 81.2 MUm; left
      eye, 419.0 +/- 68.1 MUm), and the mean FT was 243.8 +/- 35.2 MUm (right eye,
      248.8 +/- 22.0 MUm; left eye, 239.1 +/- 44.6 MUm). There was a significant
      positive correlation between the serum VEGF level and subfoveal CT (right eye, r
      = 0.58, p = 0.021; left eye, r = 0.60, p = 0.012), but the correlation between
      the level of serum VEGF and FT was not significant (right eye, r = 0.007, p >
      0.05; left eye, r = 0.25, p > 0.05). CONCLUSIONS: The significant correlation
      between the serum VEGF level and subfoveal CT in patients with POEMS syndrome
      suggests that choroidal thickness is influenced by the level of serum VEGF. These
      results not only aid in an understanding of the pathogenesis of ocular changes in
      patients with POEMS syndrome, but also offer clues regarding the pathogenesis of
      other choroidal diseases.

PMID- 25367834
TI  - Targeting a dynamic protein-protein interaction: fragment screening against the
      malaria myosin A motor complex.
AB  - Motility is a vital feature of the complex life cycle of Plasmodium falciparum,
      the apicomplexan parasite that causes human malaria. Processes such as host cell
      invasion are thought to be powered by a conserved actomyosin motor (containing
      myosin A or myoA), correct localization of which is dependent on a tight
      interaction with myosin A tail domain interacting protein (MTIP) at the inner
      membrane of the parasite. Although disruption of this protein-protein interaction
      represents an attractive means to investigate the putative roles of myoA-based
      motility and to inhibit the parasitic life cycle, no small molecules have been
      identified that bind to MTIP. Furthermore, it has not been possible to obtain a
      crystal structure of the free protein, which is highly dynamic and unstable in
      the absence of its natural myoA tail partner. Herein we report the de novo
      identification of the first molecules that bind to and stabilize MTIP via a
      fragment-based, integrated biophysical approach and structural investigations to
      examine the binding modes of hit compounds. The challenges of targeting such a
      dynamic system with traditional fragment screening workflows are addressed
      throughout. 

PMID- 25367836
TI  - Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration:
      design, characterization, and in vivo study.
AB  - Cancer nanotherapeutics is beginning to overwhelm the global research and viewed
      to be the revolutionary treatment regime in the medical field. This investigation
      describes the development of a stable nanostructured lipid carrier (NLC) system
      as a carrier for curcumin (CRM). The CRM-loaded NLC developed as a particle with
      the size of 146.8 nm, a polydispersity index of 0.18, an entrapment efficiency
      (EE) of 90.86%, and the zeta potential (ZP) of -21.4 mV. Besides, the increased
      cytotoxicity of CRM-NLC than that of CRM to astrocytoma-glioblastoma cell line
      (U373MG) in the cancer cell lines was observed. Results of biodistribution
      studies showed higher drug concentration in brain after intranasal administration
      of NLCs than PDS. The results of the study also suggest that CRM-NLC is a
      promising drug delivery system for brain cancer therapy. 

PMID- 25367835
TI  - Effects of a prevention program for divorced families on youth cortisol
      reactivity 15 years later.
AB  - OBJECTIVE: We examined whether an empirically based, randomised controlled trial
      of a preventive intervention for divorced mothers and children had a long-term
      impact on offspring cortisol regulation. DESIGN: Divorced mothers and children
      (age 9-12) were randomly assigned to a literature control condition or the 11
      week New Beginnings Program, a family-focused group preventive intervention for
      mothers and children in newly divorced families. MAIN OUTCOME MEASURES: Fifteen
      years after the trial, offspring salivary cortisol (n = 161) was measured before
      and after a social stress task. RESULTS: Multilevel mixed models were used to
      predict cortisol from internalizing symptoms, externalizing symptoms, group
      assignment and potential moderators of intervention effects. Across the sample,
      higher externalizing symptoms were associated with lower cortisol reactivity.
      There was a significant group-by-age interaction such that older offspring in the
      control group had higher reactivity relative to the intervention group, and
      younger offspring in the control group exhibited a decline across the task
      relative to younger offspring in the intervention group. CONCLUSIONS: Preventive
      interventions for youth from divorced families may have a long-term impact on
      cortisol reactivity to stress. Results highlight the importance of examining
      moderators of program effects.

PMID- 25367837
TI  - TIA triage in emergency department using acute MRI (TIA-TEAM): a feasibility and
      safety study.
AB  - BACKGROUND: Positive diffusion weighted imaging (DWI) on MRI is associated with
      increased recurrent stroke risk in TIA patients. Acute MRI aids in TIA risk
      stratification and diagnosis. AIM: To evaluate the feasibility and safety of TIA
      triage directly from the emergency department (ED) with acute MRI and
      neurological consultation. METHODS: Consecutive ED TIA patients assessed by a
      neurologist underwent acute MRI/MRA of head/neck per protocol and were
      hospitalized if positive DWI, symptomatic vessel stenosis, or per clinical
      judgment. Stroke neurologist adjudicated the final TIA diagnosis as definite,
      possible, or not a cerebrovascular event. Stroke recurrence rates were calculated
      at 7, 90, 365 days and compared with predicted stroke rates derived from
      historical DWI and ABCD(2) score data. RESULTS: One hundred twenty-nine enrolled
      patients had a mean age of 69 years (+/- 17) and median ABCD(2) score of 3
      (interquartile range [IQR] 3-4). During triage, 112 (87%) patients underwent
      acute MRI after a median of 16 h (IQR 10-23) from symptom onset. No patients
      experienced a recurrent event before imaging. Twenty-four (21%) had positive DWI
      and 8 (7%) had symptomatic vessel stenosis. Of the total cohort, 83 (64%) were
      discharged and 46 (36%) were hospitalized. By one-year follow-up, one patient in
      each group had experienced a stroke. Of 92 patients with MRI and index
      cerebrovascular event, recurrent stroke rates were 1.1% at 7 and 90 days. These
      were similar to predicted recurrence rates. CONCLUSION: TIA triage in the ED
      using a protocol with neurological consultation and acute MRI is feasible and
      safe. The majority of patients were discharged without hospitalization and rates
      of recurrent stroke were not higher than predicted.

PMID- 25367839
TI  - FAI Update 2014.

PMID- 25367838
TI  - Inducing axial chirality in a "Gelander" oligomer by length mismatch of the
      oligomer strands.
AB  - Helical molecules are not only esthetically appealing due to their structural
      beauty, they also display unique physical properties as a result of their
      chirality. We describe herein a new approach to "Gelander" oligomers by
      interlinking two oligomer strands of different length. To compensate for the
      dimensional mismatch, the longer oligo(benzyl ether) oligomer wraps around the
      oligophenyl backbone. The new "Gelander" oligomer 1 was assembled in a sequence
      of functional-group transformations and cross-coupling steps followed by final
      cyclizations based on nucleophilic substitution reactions, and was fully
      characterized, including X-ray diffraction analysis. The isolation of pure
      enantiomers enabled the racemization process to be studied by circular dichroism
      spectroscopy. 

PMID- 25367840
TI  - Opioid use and abuse.

PMID- 25367842
TI  - No ECSIT-stential evidence for a link with Alzheimer's disease yet (retrospective
      on DOI 10.1002/bies.201100193).

PMID- 25367843
TI  - Amine-boranes: green hypergolic fuels with consistently low ignition delays.
AB  - Complexation of amines with borane converts them to hypergols or decreases their
      ignition delays (IDs) multifold (with white fuming nitric acid as the oxidant).
      With consistently low IDs, amine-boranes represent a class of compounds that can
      be promising alternatives to toxic hydrazine and its derivatives as propellants.
      A structure-hypergolicity relationship study reveals the necessary features for
      the low ID. 

PMID- 25367844
TI  - Classification of sodium MRI data of cartilage using machine learning.
AB  - PURPOSE: To assess the possible utility of machine learning for classifying
      subjects with and subjects without osteoarthritis using sodium magnetic resonance
      imaging data. Theory: Support vector machine, k-nearest neighbors, naive Bayes,
      discriminant analysis, linear regression, logistic regression, neural networks,
      decision tree, and tree bagging were tested. METHODS: Sodium magnetic resonance
      imaging with and without fluid suppression by inversion recovery was acquired on
      the knee cartilage of 19 controls and 28 osteoarthritis patients. Sodium
      concentrations were measured in regions of interests in the knee for both
      acquisitions. Mean (MEAN) and standard deviation (STD) of these concentrations
      were measured in each regions of interest, and the minimum, maximum, and mean of
      these two measurements were calculated over all regions of interests for each
      subject. The resulting 12 variables per subject were used as predictors for
      classification. RESULTS: Either Min [STD] alone, or in combination with Mean
      [MEAN] or Min [MEAN], all from fluid suppressed data, were the best predictors
      with an accuracy >74%, mainly with linear logistic regression and linear support
      vector machine. Other good classifiers include discriminant analysis, linear
      regression, and naive Bayes. CONCLUSION: Machine learning is a promising
      technique for classifying osteoarthritis patients and controls from sodium
      magnetic resonance imaging data.

PMID- 25367845
TI  - Thermal conductivity of organic bulk heterojunction solar cells: an unusual
      binary mixing effect.
AB  - [6,6]-Phenyl-C61-butyric acid methyl ester (PCBM), a fullerene derivative, is the
      most widely used electron acceptor in bulk-heterojunction (BHJ) organic
      photovoltaics, and its concentration is usually tuned to achieve optimal device
      performance. However, PCBM loading can significantly impair the thermal transport
      performance of the BHJs due to its ultra-low thermal conductivity (0.03-0.07 W m(
      1) K(-1)). In this work, we study the thermal conductivity of BHJs as a function
      of the PCBM concentration using time domain thermoreflectance. The thermal
      conductivities of BHJs composed of PCBM blended with donor polymers from the
      PBDTTT family with different side chains systematically deviate from those
      predicted by effective medium theory. Evidence presented in this work indicates
      that for these copolymers, only when the polymer concentration reaches a
      threshold value (~30 to 35% volumetric fraction), does the thermal conductivity
      BHJ film start to increase, possibly due to the formation of high thermal
      conductivity percolation pathways. 

PMID- 25367846
TI  - Epidermal electronics with advanced capabilities in near-field communication.
AB  - Epidermal electronics with advanced capabilities in near field communications
      (NFC) are presented. The systems include stretchable coils and thinned NFC chips
      on thin, low modulus stretchable adhesives, to allow seamless, conformal contact
      with the skin and simultaneous capabilities for wireless interfaces to any
      standard, NFC-enabled smartphone, even under extreme deformation and after/during
      normal daily activities. 

PMID- 25367847
TI  - Emotional adjustment over 1 year post-diagnosis in patients with cancer:
      understanding and predicting adjustment trajectories.
AB  - PURPOSE: The aim of this study was to determine the prevalence of basic
      trajectories in emotional adjustment in cancer survivors and identify predictors
      of long-term change. METHODS: We assessed 421 patients with cancer after
      diagnosis and 6 and 12 months later. Measures comprised anxiety, depression,
      perceived support, desired support, and illness intrusiveness. RESULTS: Anxiety
      decreased over time, whereas depression increased as did need for support. About
      one third of initial diagnostic classifications (into low distress, symptoms, or
      clinical level of distress) changed from one assessment to the next. Lower age
      and higher illness intrusiveness predicted which patient showed worse adjustment
      over time. CONCLUSION: To avoid both over- and undertreatment of distressed
      individuals, repeated measurements are needed to identify actual adjustment
      trajectories. Initial assessment of emotional reaction to a diagnosis is not a
      reliable predictor of long-term adjustment. Patients should be made aware that
      completion of initial medical treatment even when accompanied by a positive
      prognosis does not in and of itself forecast how well patients adjust during
      survivorship.

PMID- 25367848
TI  - Selective Medial Prefrontal Cortex Responses During Live Mutual Gaze Interactions
      in Human Infants: An fNIRS Study.
AB  - To investigate the role of the prefrontal cortex (PFC) in processing multimodal
      communicative ostensive signals in infants, we measured cerebral hemodynamic
      responses by using near-infrared spectroscopy (NIRS) during the social
      interactive play "peek-a-boo", in which both visual (direct gaze) and auditory
      (infant-directed speech) stimuli were presented. The infants (mean age, around 7
      months) sat on their mother's lap, equipped with an NIRS head cap, and looked at
      a partner's face during "peek-a-boo". An eye-tracking system simultaneously
      monitored the infants' visual fixation patterns. The results indicate that, when
      the partner presented a direct gaze, rather than an averted gaze, toward an
      infant during social play, the infant fixated on the partner's eye region for a
      longer duration. Furthermore, hemodynamic activity increased more prominently
      dorsomedial prefrontal cortex (mPFC) in response to social play with a partner's
      direct gaze compared to an averted gaze. In contrast, hemodynamic activity
      increased in the right dorsolateral prefrontal cortex (R-lPFC) regardless of a
      partner's eye gaze direction. These results indicate that a partner's direct gaze
      shifts an infant's attention to the partner's eyes for interactive communication,
      and specifically activates the mPFC. The differences in hemodynamic responses
      between the mPFC and R-lPFC suggest functional differentiation within the PFC,
      and a specific role of the mPFC in the perception of face-to-face communication,
      especially in mutual gaze, which is essential for social interaction.

PMID- 25367849
TI  - X-linked inhibitor of apoptosis-associated factor l (XAFl) enhances the
      sensitivity of colorectal cancer cells to cisplatin.
AB  - The purpose of present study was to investigate the roles of X-linked inhibitor
      of apoptosis-associated factor l (XAFl) in regulation apoptosis of colorectal
      cancer (CRC) cells after treatment with cisplatin (DDP). A total of ten paired
      cancerous and non-cancerous tissues were collected from patients with CRC after
      surgery. The levels of XAFl protein were detected by Western blot. Primary CRC
      cells were separated from cancer tissues, and its viability or apoptosis after
      treatment with DDP was determined with MTT or Annexin V/PI assays, respectively.
      Furthermore, we either up-regulated transfecting a XAF1 overexpression vector or
      down-regulated XAF1 by siRNA interference. And then, the XAF1 levels and its
      sensitivity to cisplatin were assessed. XAFl had a lower expression in the
      cancerous tissues from samples T1, T2 and T3 than their paired non-cancerous
      tissues N1, N2 and N3. However, the expression of XAF1 was not detected in
      samples T4 and N1. XAF1 levels in cancer tissues significantly decreased in
      comparison with normal tissues. Cell abilities of primary cells were
      significantly decreased in a dose-dependent manner, after treatment with a series
      concentrations of cisplatin (2, 5, 10 MUg/mL) for 48 h. Although, after down
      expression of XAFl by siRNA, cisplatin caused a significant decreases in
      apoptosis rates in CRC cells. The up-regulation of XAF1 distinctly increased
      apoptosis in CRC cells administered by cisplatin (P < 0.001). The XAFl could
      promoted apoptosis and enhanced chemotherapy sensitivity to cisplatin in CRC
      cells.

PMID- 25367850
TI  - Pokemon enhances proliferation, cell cycle progression and anti-apoptosis
      activity of colorectal cancer independently of p14ARF-MDM2-p53 pathway.
AB  - Pokemon has been showed to directly suppress p14(ARF) expression and also to
      overexpress in multiple cancers. However, p14(ARF)-MDM2-p53 pathway is usually
      aberrant in colorectal cancer (CRC). The aim is to confirm whether Pokemon plays
      a role in CRC and explore whether Pokemon works through p14(ARF)-MDM2-p53 pathway
      in CRC. Immunohistochemistry for Pokemon, p14(ARF) and Mtp53 protein was applied
      to 45 colorectal epitheliums (CREs), 42 colorectal adenomas (CRAs) and 66 CRCs.
      Pokemon was knocked down with RNAi technique in CRC cell line Lovo to detect mRNA
      expression of p14(ARF) with qRT-PCR, cell proliferation with CCK8 assay, and cell
      cycle and apoptosis with flowcytometry analysis. The protein expression rates
      were significantly higher in CRC (75.8%) than in CRE (22.2 %) or CRA (38.1%) for
      Pokemon and higher in CRC (53.0%) than in CRE (0) or CRA (4.8%) for Mtp53, but
      not significantly different in CRC (86.4 %) versus CRE (93.3%) or CRA (90.5 %)
      for p14(ARF). Higher expression rate of Pokemon was associated with lymph node
      metastasis and higher Duke's stage. After knockdown of Pokemon in Lovo cells, the
      mRNA level of p14(ARF) was not significantly changed, the cell proliferation
      ability was decreased by 20.6%, cell cycle was arrested by 55.7% in G0/G1 phase,
      and apoptosis rate was increased by 19.0%. Pokemon enhanced the oncogenesis of
      CRC by promoting proliferation, cell cycle progression and anti-apoptosis
      activity of CRC cells independently of p14(ARF)-MDM2-p53 pathway. This finding
      provided a novel idea for understanding and further studying the molecular
      mechanism of Pokemon on carcinogenesis of CRC.

PMID- 25367852
TI  - Three dysregulated microRNAs in serum as novel biomarkers for gastric cancer
      screening.
AB  - Gastric cancer (GC) is one of the most threatening diseases. The symptoms of GC
      are complex and hard to detect, which also contribute to the poor prognosis of
      GC. Besides, the current diagnosis for GC is expensive and invasive. Thus, a
      fast, noninvasive biomarker is urgently needed for GC screening. MicroRNAs
      (miRNAs) are small noncoding RNAs, which are involved in a great variety of
      pathological processes, particularly carcinogenesis. MiRNAs are stable in gastric
      juice, plasma as well as serum, which facilitate it to be a promising biomarker
      for cancer. In this study, we selected three novel miRNAs, i.e., miR-233, miR-16,
      and miR-100, to investigate their potential diagnostic value in GC screening. A
      total of 50 GC patients and 47 healthy controls were involved in this study.
      Blood serum samples were collected; RNAs were extracted and normalized with U6
      snRNA as the internal control; qRT-PCR was performed for relative expression of
      target miRNAs. Levels of miRNAs expression were compared by Student's t test for
      the comparison between two groups, and one-way ANOVA was used for multiple
      comparisons. The expression of miR-223, miR-16, and miR-100 was all significantly
      higher in GC patients than controls (all P < 0.001). All the tested miRNAs were
      manifested to be valuable biomarkers for GC. Relative expression of these miRNAs
      was significantly correlated with clinical characteristics of GC patients, such
      as TNM stage (P = 0.036 for miR-223; P < 0.001 for miR-100), metastatic status (P
      = 0.045 for miR-223; P = 0.031 for miR-16; P = 0.006 for miR-100), tumor size (P
      = 0.042 for miR-223; P = 0.031 for miR-16; P < 0.001 for miR-100), and
      differentiation grade (P = 0.036 for miR-223; P = 0.030 for miR-16; P = 0.034 for
      miR-100). However, in T classification, which considered both tumor size and
      direct extent of primary tumor, the difference in target miRNAs expression was
      not significant. In summary, we confirmed the diagnostic value of serum miR-223,
      miR-16, and miR-100 in GC. Significantly elevated expression of the three miRNAs
      was also observed in advanced GC patients, which suggested their availability in
      cancer staging.

PMID- 25367851
TI  - Negative feedback of miR-29 family TET1 involves in hepatocellular cancer.
AB  - Primary hepatocellular carcinoma (HCC) is the most common form of liver cancer
      and is one of the most common malignancies worldwide. Tumor suppressor gene
      silencing through DNA methylation contributes to cancer formation. The ten-eleven
      translocations (TET) family of alpha-ketogluta-rate-dependent dioxygenases
      catalyzes the sequential oxidation of 5-methylcytosine to 5-hydroxymethyl
      cytosine, 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA
      demethylation. MicroRNAs are an abundant class of 17-25 nucleotides small
      noncoding RNAs, identified as important regulators of many diverse biological
      processes. In this study, we showed that TET1 expression was obviously reduced in
      the majority of examined HCC tissues. And we further investigated the expression
      and functional involvement of TET1 in proliferation, migration and invasion, and
      determined that TET1 may function as a tumor suppressor. MiR-29b was proved to
      inhibit metastasis through the targeting of TET1, indicating that downregulation
      of miR-29 may involve in HCC carcinogenesis and progression through potentiation
      of TET1 expression. Thus, we elucidated the roles of feedback of miR-29-TET1
      downregulation in HCC development and suggested a potential target in
      identification of the prognosis and application of cancer therapy for HCC
      patients. 

PMID- 25367853
TI  - Two polymorphisms of USF1 gene (-202G>A and -844C>T) may be associated with
      hepatocellular carcinoma susceptibility based on a case-control study in Chinese
      Han population.
AB  - Hepatocellular carcinoma (HCC) is a prototype of liver cancer, which is closely
      related to manifested metabolism of lip and glucose. Upstream transcription
      factor 1 (USF1) is an important transcription factor in human genome, and it
      regulates the expression of multiple genes associated with lipid and glucose
      metabolism. This study aims at investigating the correlation between seven common
      USF1 polymorphisms (i.e., -1994 G>A, -202 G>A, 7998 A>G, -844 C>T, 9042 C>G, 9441
      T>C, and -2083 G>A) and the risk of HCC. Elucidation of the interaction might be
      of vital importance to the diagnosis and prognosis of HCC. One hundred and fifty
      five HCC patients and 160 healthy controls from a Chinese Han population were
      involved in this study. Tag single-nucleotide polymorphisms (SNPs) were
      identified with reference to CBI-dbSNP and HapMap databases. DNA was extracted
      from blood samples, and matrix-assisted laser desorption-ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) was conducted to determine the
      polymorphisms of USF1. Odds ratio (OR) and 95% confidence interval were applied
      to evaluate the difference of genotype distribution. Seven SNPs were selected to
      be representatives. No significant difference was observed concerning -1994 G>A,
      7998 A>G, 9042 C>G, 9441 T>C, and -2083 G>A polymorphisms (all P > 0.05). A
      significantly elevated genotype frequency regarding -202 G>A polymorphism was
      observed in HCC patients [AA vs. GG: OR 2.13 (1.13-4.01), P = 0.019; AA vs.
      GG+GA: OR 2.22 (1.32-3.75), P = 0.003; A allele vs. G allele: OR 1.46 (1.07
      2.01), P = 0.018]. Subjects carrying mutant -844 C>T genotypes also had a higher
      risk of HCC [CT vs. CC: OR 1.88 (1.17-3.04), P = 0.009; CT+TT vs. CC: OR 1.83
      (1.17-2.86), P = 0.008; T allele vs. C allele: OR 1.49 (1.06-2.09), P = 0.020].
      Further studies are recommended to validate our findings in different ethnicity
      and to clarify the functional relationship between USF1 polymorphisms and the
      susceptibility of HCC.

PMID- 25367854
TI  - Re-challenge with catumaxomab in patients with malignant ascites: results from
      the SECIMAS study.
AB  - Malignant ascites is a common phenomenon in cancer patients. It poses a great
      challenge to the clinician, because of limited treatment options and strong
      impairment of the quality of life of the often palliative patients. The SECIMAS
      study investigated the feasibility of a re-challenge with four catumaxomab
      intraperitoneal infusions in patients who had already received a first cycle of
      four infusions in the phase III CASIMAS study, which compared catumaxomab with
      and without prednisolone premedication. The primary endpoint was the proportion
      of patients who received at least three catumaxomab infusions. Secondary
      endpoints included a composite safety score (CSS) summarising the worst grades
      for the main catumaxomab-related adverse events (pyrexia, nausea, vomiting and
      abdominal pain), safety, efficacy and the occurrence of anti-drug antibodies
      (ADAs). Eight of nine screened patients received a second catumaxomab cycle.
      Compliance with a catumaxomab re-challenge was high: all eight patients (100%)
      received all four infusions. The median CSS was 3.0 versus 3.4 in CASIMAS. The
      tolerability profile of the second catumaxomab cycle was comparable to that of
      the first cycle. Median puncture-free survival (48 days) and overall survival
      (407 days) were longer than in CASIMAS (35 and 103 days, respectively), although
      median time to next puncture was shorter (60 vs. 97 days). Of six patients
      sampled, all were ADA positive at screening and remained ADA positive until the
      end of the study. The presence of ADAs did not affect catumaxomab's safety or
      efficacy. The CSS and tolerability profile for catumaxomab in SECIMAS were
      comparable to those in CASIMAS. The majority of patients benefitted from a second
      cycle of catumaxomab. A re-challenge seems to be feasible and safe for selected
      patients with recurrent malignant ascites due to carcinoma after a first cycle of
      catumaxomab.

PMID- 25367855
TI  - Blood neutrophil-lymphocyte ratio predicts survival in locally advanced cancer
      stomach treated with neoadjuvant chemotherapy FOLFOX 4.
AB  - Accurate predictors of survival for patients with advanced gastric cancer treated
      with neoadjuvant chemotherapy are currently lacking. In this study, we aimed to
      evaluate the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in
      patients with stage III-IV gastric cancer who received neoadjuvant chemotherapy
      FOLFOX 4 as neoadjuvant chemotherapy. We enrolled 70 patients with stage III-IV
      cancer stomach in this study. Patients received FOLFOX 4 as neoadjuvant
      chemotherapy. Blood sample was collected before chemotherapy. The NLR was divided
      into two groups: high (>3) and low (<= 3). Univariate analysis on progression
      free survival (PFS) and overall survival (OS) was performed using the Kaplan
      Meier and log-rank tests, and multivariate analysis was conducted using the Cox
      proportional hazards regression model. The toxicity was evaluated according to
      National Cancer Institute Common Toxicity Criteria. The univariate analysis
      showed that PFS and OS were both worse for patients with high NLR than for those
      with low NLR before chemotherapy (median PFS 28 and 44 months, respectively, P =
      0.001; median OS 30 and 48 months, P = 0.001). Multivariate analysis showed that
      NLRs before chemotherapy were independent prognostic factors of OS but not for
      progression-free survival. NLR may serve as a potential biomarker for survival
      prognosis in patients with stage III-IV gastric cancer receiving neoadjuvant
      chemotherapy. The FOLFOX 4 demonstrated an acceptable toxicity.

PMID- 25367856
TI  - MR imaging in hepatocellular carcinoma: correlations between MRI features and
      molecular marker VEGF.
AB  - The aim of this paper was to investigate the correlations between magnetic
      resonance imaging (MRI) features and vascular endothelial growth factor (VEGF) in
      hepatocellular carcinoma (HCC). Thirty-six patients with HCC included in this
      study underwent dynamic contrast-enhanced MR imaging and diffusion-weighted MR
      imaging. Signal intensity characteristics of HCCs were reviewed independently by
      two experienced radiologists. ADC maps were automatically computed. VEGF
      expression was evaluated by immunohistochemical staining. The grades of the VEGF
      expression were correlated inversely with the ADC values of the HCCs (r = -0.435,
      p = 0.008). Intensity heterogeneity correlated with VEGF expression (r = 0.571, p
      = 0.039). There is a significant correlation between the intensity of arterial
      enhancement and VEGF expression (r = -0.386, p = 0.02). However, no correlation
      was found between the VEGF grades and the intensity of enhancement in the hepatic
      portal venous and late phases, as well as equilibrium phase. Our results indicate
      that ADC value on DW-MRI, the signal intensity in arterial phase and intensity
      heterogeneity correlate with the degree of VEGF expression in hepatocellular
      carcinomas.

PMID- 25367857
TI  - Microtubules contribute to tubule elongation and anchoring of endoplasmic
      reticulum, resulting in high network complexity in Arabidopsis.
AB  - The endoplasmic reticulum (ER) is a network of tubules and sheet-like structures
      in eukaryotic cells. Some ER tubules dynamically change their morphology, and
      others form stable structures. In plants, it has been thought that the ER tubule
      extension is driven by the actin-myosin machinery. Here, we show that
      microtubules also contribute to the ER tubule extension with an almost 20-fold
      slower rate than the actin filament-based ER extension. Treatment with the actin
      depolymerizing drug Latrunculin B made it possible to visualize the slow
      extension of the ER tubules in transgenic Arabidopsis (Arabidopsis thaliana)
      plants expressing ER-targeted green fluorescent protein. The ER tubules elongated
      along microtubules in both directions of microtubules, which have a distinct
      polarity. This feature is similar to the kinesin- or dynein-driven ER tubule
      extension in animal cells. In contrast to the animal case, ER tubules elongating
      with the growing microtubule ends were not observed in Arabidopsis. We also found
      the spots where microtubules are stably colocalized with the ER subdomains during
      long observations of 1,040 s, suggesting that cortical microtubules contribute to
      provide ER anchoring points. The anchoring points acted as the branching points
      of the ER tubules, resulting in the formation of multiway junctions. The density
      of the ER tubule junction positively correlated with the microtubule density in
      both elongating cells and mature cells of leaf epidermis, showing the requirement
      of microtubules for formation of the complex ER network. Taken together, our
      findings show that plants use microtubules for ER anchoring and ER tubule
      extension, which establish fine network structures of the ER within the cell. 

PMID- 25367858
TI  - The nitrate transporter MtNPF6.8 (MtNRT1.3) transports abscisic acid and mediates
      nitrate regulation of primary root growth in Medicago truncatula.
AB  - Elongation of the primary root during postgermination of Medicago truncatula
      seedlings is a multigenic trait that is responsive to exogenous nitrate. A
      quantitative genetic approach suggested the involvement of the nitrate
      transporter MtNPF6.8 (for Medicago truncatula NITRATE TRANSPORTER1/PEPTIDE
      TRANSPORTER Family6.8) in the inhibition of primary root elongation by high
      exogenous nitrate. In this study, the inhibitory effect of nitrate on primary
      root elongation, via inhibition of elongation of root cortical cells, was
      abolished in npf6.8 knockdown lines. Accordingly, we propose that MtNPF6.8
      mediates nitrate inhibitory effects on primary root growth in M. truncatula.
      pMtNPF6.8:GUS promoter-reporter gene fusion in Agrobacterium rhizogenes-generated
      transgenic roots showed the expression of MtNPF6.8 in the pericycle region of
      primary roots and lateral roots, and in lateral root primordia and tips. MtNPF6.8
      expression was insensitive to auxin and was stimulated by abscisic acid (ABA),
      which restored the inhibitory effect of nitrate in npf6.8 knockdown lines. It is
      then proposed that ABA acts downstream of MtNPF6.8 in this nitrate signaling
      pathway. Furthermore, MtNPF6.8 was shown to transport ABA in Xenopus spp.
      oocytes, suggesting an additional role of MtNPF6.8 in ABA root-to-shoot
      translocation. (15)NO3(-)-influx experiments showed that only the inducible
      component of the low-affinity transport system was affected in npf6.8 knockdown
      lines. This indicates that MtNPF6.8 is a major contributor to the inducible
      component of the low-affinity transport system. The short-term induction by
      nitrate of the expression of Nitrate Reductase1 (NR1) and NR2 (genes that encode
      two nitrate reductase isoforms) was greatly reduced in the npf6.8 knockdown
      lines, supporting a role of MtNPF6.8 in the primary nitrate response in M.
      truncatula.

PMID- 25367860
TI  - A retrospective analysis of skin bacterial colonisation, susceptibility and
      resistance in atopic dermatitis and impetigo patients.
AB  - Atopic dermatitis (AD) and impetigo are skin conditions where bacterial
      colonisation and infection, especially with Staphylococcus aureus play an
      important role. We compared skin bacterial population, resistance patterns and
      choice of antimicrobial agents in patients diagnosed with AD and impetigo during
      2005 and 2011 in our department. Number of positive cultures in the AD group were
      40 and 53 in 2005 and 2011, with S. aureus found in 97.5% and 100%, respectively.
      Differences in resistance were marginal. In impetigo, S. aureus was found in all
      70 patients in 2005 and all 40 patients in 2011. Antibiotic resistance to
      specifically fusidic acid was more common in 2005 impetigo patients (22.8%)
      versus 2011 (5%) (p = 0.078). The most commonly used oral antimicrobial was
      cefadroxil (in 57.5% and 52.8% of AD and 58.6% and 35% of impetigo patients in
      2005 and 2011, respectively). Our observations confirm the high prevalence of S.
      aureus in both diseases and, interestingly, show a declining resistance trend in
      impetigo.

PMID- 25367861
TI  - Rare Association: Chagas' Disease and Hypertrophic Cardiomyopathy.
AB  - A woman (49 years) with Chagas' disease showed: ECG, right bundle-branch block
      and left anterior-superior fascicular block; V1 has unusual R > R', and elevated
      ST segment from V2 to V6 . Additional imaging revealed concomitant HCM and
      Chagas, which is uncommon. Overlapping of ECG findings can be explained by this
      rare association of diseases. 

PMID- 25367859
TI  - Alternative splicing-mediated targeting of the Arabidopsis GLUTAMATE RECEPTOR3.5
      to mitochondria affects organelle morphology.
AB  - Since the discovery of 20 genes encoding for putative ionotropic glutamate
      receptors in the Arabidopsis (Arabidopsis thaliana) genome, there has been
      considerable interest in uncovering their physiological functions. For many of
      these receptors, neither their channel formation and/or physiological roles nor
      their localization within the plant cells is known. Here, we provide, to our
      knowledge, new information about in vivo protein localization and give insight
      into the biological roles of the so-far uncharacterized Arabidopsis GLUTAMATE
      RECEPTOR3.5 (AtGLR3.5), a member of subfamily 3 of plant glutamate receptors.
      Using the pGREAT vector designed for the expression of fusion proteins in plants,
      we show that a splicing variant of AtGLR3.5 targets the inner mitochondrial
      membrane, while the other variant localizes to chloroplasts. Mitochondria of
      knockout or silenced plants showed a strikingly altered ultrastructure, lack of
      cristae, and swelling. Furthermore, using a genetically encoded mitochondria
      targeted calcium probe, we measured a slightly reduced mitochondrial calcium
      uptake capacity in the knockout mutant. These observations indicate a functional
      expression of AtGLR3.5 in this organelle. Furthermore, AtGLR3.5-less mutant
      plants undergo anticipated senescence. Our data thus represent, to our knowledge,
      the first evidence of splicing-regulated organellar targeting of a plant ion
      channel and identify the first cation channel in plant mitochondria from a
      molecular point of view. 

PMID- 25367862
TI  - Maize (Zea mays) seeds can detect above-ground weeds; thiamethoxam alters the
      view.
AB  - BACKGROUND: Far red light is known to penetrate soil and delay seed germination.
      Thiamethoxam as a seed treatment has been observed to enhance seed germination.
      No previous work has explored the effect of thiamethoxam on the physiological
      response of buried maize seed when germinating in the presence of above-ground
      weeds. We hypothesised that the changes in red:far red reflected from above
      ground weeds would be detected by maize seed phytochrome and delay seed
      germination by decreasing the level of GA and increasing ABA. We further
      hypothesised that thiamethoxam would overcome this delay in germination. RESULTS:
      Thiamethoxam enhanced seed germination in the presence of above-ground weeds by
      increasing GA signalling and downregulating DELLA protein and ABA signalling
      genes. An increase in amylase activity and a degradation of starch were also
      observed. CONCLUSIONS: Far red reflected from the above-ground weeds was capable
      of penetrating below the soil surface and was detected by maize seed phytochrome.
      Thiamethoxam altered the effect of far red on seed germination by stimulating GA
      and inhibiting ABA synthesis. This is the first study to suggest that the mode of
      action of thiamethoxam involves both GA synthesis and ABA inhibition.

PMID- 25367863
TI  - Longitudinal trends in utilization of endocrine therapies for breast cancer: an
      international comparison.
AB  - WHAT IS KNOWN AND OBJECTIVE: Endocrine therapy is an effective treatment for post
      menopausal women with 'oestrogen receptor-positive' invasive breast cancers.
      There are two main types of endocrine therapies: selective oestrogen receptor
      modulators (tamoxifen) and aromatase inhibitors (anastrozole, letrozole and
      exemestane). The aim of this study was to compare the patterns of use of
      endocrine therapies for breast cancer in women between nine developed countries.
      METHODS: A longitudinal, cross-national drug utilization study was conducted. The
      endocrine therapies included were tamoxifen and the aromatase inhibitors:
      anastrozole, letrozole and exemestane. Annual drug utilization data were
      collected from Australia, Denmark, England, Finland, France, Iceland, the
      Netherlands, Norway and Sweden over the period 2001-2012. Utilization was
      measured in DDD/1000 inhabitants/day and was also adjusted for breast cancer
      incidence and female population statistics. RESULTS AND DISCUSSION: Total use of
      endocrine therapies either increased or remained steady in all countries. Total
      endocrine therapy usage was consistently highest in England and France. Norway
      showed the lowest usage of endocrine therapies overall, using only 1.80 DDD/1000
      inhabitants/day in 2012. Downward trends in tamoxifen use and upward trends in
      aromatase inhibitors were seen across all countries over the study period. By
      2012, aromatase inhibitors represented over half of total endocrine therapy use
      in all countries, and as high as 74% and 80% in France and Denmark, respectively.
      WHAT IS NEW AND CONCLUSION: Our analysis found a shift in use of endocrine
      therapy from tamoxifen to aromatase inhibitors. This trend is consistent with
      major clinical guidelines endorsing preferential use of aromatase inhibitors in
      post-menopausal women. Stabilization or small increase in tamoxifen use in the
      recent years may reflect the recognition of tamoxifen as still an appropriate
      first-line treatment. The similarity in utilization patterns may be due to the
      relatively comparable healthcare systems in the countries, namely universal
      health insurance and pharmaceutical coverage. Differences in utilization observed
      could be due to differences in breast cancer incidence, prescribing behaviours,
      interpretation of new trial evidence, and timing of drug marketing approval and
      reimbursement between countries.

PMID- 25367865
TI  - Pd uptake and H2S sensing by an amphoteric metal-organic framework with a soft
      core and rigid side arms.
AB  - Molecular components of opposite character are often incorporated within a single
      system, with a rigid core and flexible side arms being a common design choice.
      Herein, molecule L has been designed and prepared featuring the reverse design,
      with rigid side arms (arylalkynyl) serving to calibrate the mobility of the
      flexible polyether links in the core. Crystallization of this molecule with
      Pb(II)  ions led to a dynamic metal-organic framework (MOF) system that not only
      exhibits dramatic, reversible single-crystal-to-single-crystal transformations,
      but combines distinct donor and acceptor characteristics, allowing for
      substantial uptake of PdCl2 and colorimetric sensing of H2 S in water. 

PMID- 25367864
TI  - Prospective cohort study of a new vacuum delivery device to assist with
      complicated labour in low-resource settings.
AB  - OBJECTIVES: Currently available vacuum devices used to assist women undergoing
      complicated labour are unsuitable for use in low-resource settings. The objective
      of this study was to evaluate the safety and feasibility of a new low-cost vacuum
      device, named Koohi Goth Vacuum Delivery System (KGVDS), designed for use in low
      resource settings. METHODS: A hospital-based, multicentre, prospective cohort
      study with no control group was conducted in Karachi, Pakistan. After training,
      KGVDS devices were made available for use by labour room staff at their
      discretion when instrumental delivery was indicated. Women to whom KGVDS was
      applied were followed from the start of labour until discharge. Feasibility was
      assessed in terms of successful expulsion of the foetal head following
      application of KGVDS and ease of use ratings. Safety was assessed by observing
      maternal and newborn post-delivery outcomes prior to discharge. RESULTS: Koohi
      Goth Vacuum Delivery System was applied to 137 women requiring instrumental
      delivery, of whom 111 (81%; 95% CI = 74-88%) successfully expelled the foetal
      head assisted by KGVDS and 103 (75%) stated that they would agree to use KGVDS
      again. There were no serious maternal or neonatal injuries or infections related
      to KGVDS use. The mean score for 'ease of use' given by doctors and midwives
      using the device was 8 of 10. CONCLUSIONS: Koohi Goth Vacuum Delivery System was
      feasible and safe to use for assisting complicated deliveries in low-resource
      hospitals in this initial evaluation. Our results indicate that this new device
      may have the potential to improve birth outcomes in settings where most mortality
      occurs and that further evaluations should be conducted.

PMID- 25367866
TI  - Thirteen-year outcomes in the Anatomique Benoist Girard II hip prosthesis.
AB  - BACKGROUND: The Stryker Anatomique Benoist Girard (ABG) hip implant system was a
      commonly used cementless prosthesis in the early 2000s, which fell from favour
      after several studies emerged implicating the prosthesis in high rates of
      revision. This retrospective, single-surgeon clinical study examines the fracture
      rate, revision rate and reasons for revision in 500 consecutive ABG II primary
      total conventional hip replacements. METHODS: Follow-up was conducted by audit of
      patient notes, patient mailout survey, patient phone contact and audit of the
      Australian National Joint Replacement Registry (NJRR) database to find instances
      of fracture and revision. End points were periprosthetic fracture and revision
      for any reason. RESULTS: Follow-up was 1.2-13.8 years with a mean of 6.58 years.
      Of the 500 hips, 17 (3.4%) had undergone a revision. Of these, 13 were due to
      periprosthetic fracture. Four further fractures occurred that were not revised.
      Eight of these periprosthetic fractures occurred within 1 year post-operatively.
      There were four revisions for recurrent dislocations. Kaplan-Meier survival curve
      demonstrates a 93.7% survivorship at 6.58 years for revision for any reason.
      Multivariate analysis showed the only statistically significant factor for
      increased risk of revision was smaller stem size. CONCLUSION: Our results were
      consistent with the literature in that the ABG II system has good medium-term
      results but is prone to periprosthetic fractures, especially in the early post
      operative period. When used as a primary total hip arthroplasty, the ABG II
      system has an 8-year revision rate of 5.6% compared with the 4.9% of all primary
      total hip arthroplasties.

PMID- 25367867
TI  - A domino reaction of tetrahalo-7,7-dimethoxybicyclo[2.2.1]heptenyl alcohols
      leading to indenones and a de novo synthesis of ninhydrin derivatives.
AB  - An efficient acid induced rearrangement of a tetrahalo-7,7
      dimethoxybicyclo[2.2.1]heptenyl system leading to substituted indenones is
      reported. This domino reaction involves dehydration, olefin isomerization, ketal
      hydrolysis, [3,3]-sigmatropic rearrangement and dehydrohalogenation. The
      resultant vicinal dihalo olefin moiety in the efficiently generated indenone
      derivatives was utilized to transform into ninhydrin derivatives by employing
      Ru(III)-catalyzed oxidation.

PMID- 25367868
TI  - Is the mean platelet volume a predictive marker for the diagnosis of acute
      pyelonephritis in children?
AB  - BACKGROUND: Acute pyelonephritis (APN) can lead to renal scar formation, high
      blood pressure, and end-stage renal failure. Prompt and early diagnosis of APN is
      important for preventing future complications. Our goal was to study the mean
      platelet volume (MPV) as a predictor of APN in children. METHODS: The records of
      43 patients with APN and 51 patients with a lower urinary tract infection (UTI)
      were investigated prospectively. APN was confirmed using radioactive nuclide
      99mTc-DMSA scanning. The white blood cell (WBC) count, erythrocyte sedimentation
      rate (ESR), serum C-reactive protein (CRP), and MPV of both groups were measured
      and compared. RESULTS: The WBC count, MPV and ESR values, and the serum
      concentration of CRP were higher in the APN group than in the lower UTI group (p
      < 0.05). In the children with APN, the optimal cut-off value for the MPV was 8.2
      fl [area under the curve (AUC): 0.906], with sensitivity of 81.4 % and
      specificity of 86.3 %. The MPV was associated with APN (p = 0.001), and the
      sensitivity and specificity of the MPV for the diagnosis of APN were higher than
      those of the other inflammation markers. MPV > 8.2 fl yielded an adjusted OR of
      7.8 (95 % CI 3.3-18.4, p < 0.001) for APN. MPV > 8.2 fl was significantly
      associated with late renal scar formation (adjusted OR 5.7, 95 % CI 2.3-13.8, p <
      0.001). CONCLUSION: The MPV is a fast and reliable measurement with considerable
      predictive value for the diagnosis of APN and renal scars, and its predictive
      capacity is better than that of CRP, ESR, and WBC values.

PMID- 25367869
TI  - Low-intensity focused ultrasound mediated localized drug delivery for liver
      tumors in rabbits.
AB  - OBJECTIVE: To explore the antitumor effects of low-intensity focused ultrasound
      (LIFU) mediated localized drug delivery of adriamycin-microbubble-PLGA
      nanoparticle complexes on rabbits VX2 liver tumor. METHODS: ADM-NMCs were
      prepared by covalent linking of ADM-PLGA nanoparticles (ADM-NPs) to the shell of
      the microbubbles. A fixed water bag filled with microbubbles was subjected to
      LIFU and non-focused ultrasound respectively, and the ultrasound images of which
      were recorded before and after ultrasonication. A total of 54 VX2 liver tumor
      burdened rabbits were divided into six groups randomly, including control, ADM
      NPs combined with LIFU, microbubbles combined with LIFU, ADM-NPs and microbubbles
      combined with LIFU, ADM-NMCs combined with LIFU and ADM-NMCs combined with Non
      FUS. The tumor volume and volume inhibition rate (VIR) of tumor progression were
      calculated and compared. Apoptotic cells were labeled by terminal deoxyuridine
      nick end. Proliferating cell nuclear antigen was detected by
      immunohistochemistry. The median survival time of the animals were recorded and
      compared. RESULTS: ADM-NMCs were successfully prepared with an average diameter
      of 1721 nm. The highest VIR and apoptotic index (AI) were found in the group of
      ADM-NMCs combined with LIFU while the lowest proliferating index (PI) was
      simultaneously observed in this group. The median survival time of the rabbits in
      the ADM-NMCs combined with LIFU group was the longest (71days) among all groups.
      CONCLUSIONS: ADM-NMCs combined with LIFU could inhibit the rabbits VX2 liver
      tumor progress by delaying the tumor proliferation and accelerating apoptosis,
      which presents a novel process for liver tumor targeting chemotherapy.

PMID- 25367870
TI  - An enolate-mediated organocatalytic azide-ketone [3+2]-cycloaddition reaction:
      regioselective high-yielding synthesis of fully decorated 1,2,3-triazoles.
AB  - An enolate-mediated organocatalytic azide-ketone [3+2]-cycloaddition (OrgAKC)
      reaction of a variety of enolizable arylacetones and deoxybenzoins with aryl
      azides was developed for the synthesis of fully decorated 1,4-diaryl-5
      methyl(alkyl)-1,2,3-triazoles in excellent yields with high regioselectivity at
      25  degrees C for 0.5-6 h. This reaction has an excellent outcome with reference
      to reaction rate, yield, regioselectivity, operation simplicity, and availability
      of substrates and catalyst. This reaction has advantages over the previously
      known metal-mediated reactions. 

PMID- 25367871
TI  - Five 8-hydroxyquinolinate-based coordination polymers with tunable structures and
      photoluminescent properties for sensing nitroaromatics.
AB  - Using two 8-hydroxyquinolinate ligands (L1-MOM and L2-MOM) containing 3-pyridyl
      or 4-pyridyl groups, five novel coordination polymers, namely, [Zn3(L1)6] (1),
      [Zn(L1)2].2MeOH (2), [Zn(L2)2] (3), [Cd(L2)2] (4), and [Cd4(L1)6].13H2O (5), were
      synthesized and characterized by a variety of techniques. Single-crystal X-ray
      structures have revealed that these coordination polymers exhibit a structural
      diversification due to the different choices of metal salts and the effect of
      pyridyl nitrogen position. Compounds 1-5 exhibited different fluorescence
      emissions and lifetimes upon excitation in the solid state. The sensing behavior
      of these polymers was also investigated upon exposure to vapors of various
      nitroaromatic molecules (analytes). The results show that all five polymers are
      capable of sensing these nitroaromatic molecules in the vapor phase through
      fluorescence quenching. Interestingly, 3 exhibits superior sensitivity to the
      analytes in comparison with other polymers. 2-Nitrotoluene quenches the emission
      of 3 by as much as 96%.

PMID- 25367872
TI  - Investigation of out-of-plane structural properties of a graphene monolayer with
      gap-plasmons: mode-selective Raman enhancement and the influence of additional
      sp(3) type defects.
AB  - We report that Raman enhancements of a graphene monolayer sandwiched at the Au
      nanoparticle-Au thin film junction are different and can be attributed to the
      influence of a z-polarized incident field. Closer to the center of the junction,
      radial breathing like-mode (RBLM) shows dramatic Raman enhancement in terms of
      the coincidence between the z-polarized incident field formed at the junction and
      the RBLM phonon axis. The appearance of an additional D* peak can be identified
      and is attributed to the additional out-of-plane sp(3) type defect signal.
      Correlating I(D*)/I(D) with RBLM intensity variation further substantiates that
      the observed D* peak is ascribed to another out-of-plane structural defect
      signal. 

PMID- 25367875
TI  - Differences in expression of proliferation-associated genes and RANKL across the
      menstrual cycle in estrogen receptor-positive primary breast cancer.
AB  - The purpose of this study is to determine if there are differences in the
      expression of estrogen-regulated genes (ERGs), proliferation-associated genes and
      the progesterone effector RANKL, in premenopausal ER+ breast cancer as a result
      of the major changes in hormone levels that occur through the menstrual cycle.
      Primary ER+ tumours from 174 patients were assigned to one of three menstrual
      cycle windows: W1 (days 27-35 + 1-6), W2 (days 7-16) and W3 (days 17-26). RNA
      expression of 42 genes, including 24 putative genes associated with plasma E2
      levels, seven proliferation genes and RANKL was measured. Expression of PGR,
      TFF1, GREB1 and PDZK1 followed the previously reported pattern: a higher level in
      W2 compared to W1 while W3 had an intermediate value, mirroring changes in plasma
      estradiol. Of the other 20 ERGs, four (RUNX1, AGR2, SERPINA3 and SERPINA5) showed
      significant differences (p = 0.009-0.049) in expression across the menstrual
      cycle. The expression of six of seven proliferation-associated genes varied
      across the cycle but differently from the ERGs, being 20-35 % lower in W3
      compared to W1 and W2 (p = 0.004-0.031). Expression of RANKL was 2.5 to 3-fold
      highest in W3 (p = 0.0001) and negatively correlated to the expression of the
      proliferation-associated genes (r = -0.37; p < 0.0001). Expression of
      proliferation-associated genes and RANKL in ER+ breast tumours varies across the
      menstrual cycle showing a different rhythm to that of ERGs. This may affect the
      interpretation of gene expression profiles but may be exploitable as an
      endogenous test of endocrine responsiveness. 

PMID- 25367873
TI  - Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4.
AB  - OBJECTIVE: IBD is a group of complex, systemic disorders associated with
      intestinal inflammation and extraintestinal manifestations. Recent studies
      revealed Mendelian forms of IBD, which contributed significantly to our
      understanding of disease pathogenesis and the heritability of IBD. DESIGN: We
      performed exome sequencing in a family with Crohn's disease (CD) and severe
      autoimmunity, analysed immune cell phenotype and function in affected and non
      affected individuals, and performed in silico and in vitro analyses of cytotoxic
      T lymphocyte-associated protein 4 (CTLA-4) structure and function. RESULTS: A
      novel missense variant was identified in CTLA4 encoding CTLA-4, a coinhibitory
      protein expressed by T cells and required for regulation of T cell activation.
      The residue affected by the mutation, CTLA-4 Tyr60, is evolutionarily highly
      conserved, and the identified Y60C variant is predicted to affect protein folding
      and structural stability and demonstrated to cause impaired CTLA-4 dimerisation
      and CD80 binding. Intestinal inflammation and autoimmunity in carriers of CTLA-4
      Y60C exhibit incomplete penetrance with a spectrum of clinical presentations
      ranging from asymptomatic carrier status to fatal autoimmunity and intestinal
      inflammation. In a clinically affected CTLA-4 Y60C carrier, T cell proliferation
      was increased in vitro and associated with an increased ratio of memory to naive
      T cells in vivo, consistent with impaired regulation of T cell activation.
      CONCLUSIONS: Our results support the concept that variants in CTLA4 provide the
      basis for a novel Mendelian form of early-onset CD associated with systemic
      autoimmunity. Incomplete penetrance of autoimmunity further indicates the
      presence of other genetic and/or environmental modifiers.

PMID- 25367876
TI  - Electronic transport in heterostructures of chemical vapor deposited graphene and
      hexagonal boron nitride.
AB  - CVD graphene devices on stacked CVD hexagonal boron nitride (hBN) are
      demonstrated using a novel low-contamination transfer method, and their
      electrical performance is systematically compared to devices on SiO(2). An order
      of magnitude improvement in mobility, sheet resistivity, current density, and
      sustained power is reported when the oxide substrate is covered with five-layer
      CVD hBN.

PMID- 25367878
TI  - Identification and Evaluation of Serum MicroRNA-29 Family for Glioma Screening.
AB  - Glioma is one of the most common primary central nervous system tumors with high
      mortality and poor 5-year survival rate. Current diagnostic methods for glioma
      were either invasive or expensive. MicroRNAs (miRNAs) are small non-coding RNAs
      which play an important part in the regulation of gene expression. Considering
      the fact that miRNAs are stable in serum, plasma, urine, and other body fluids,
      they show great promises to be convenient and non-invasive biomarkers for
      cancers. This study aimed at evaluating the availability of serum microRNA-29
      (miR-29) family in screening of glioma. A meta-analysis was also performed to
      assess the predictive value of miR-29 family in multi-cancer screening. Serum
      samples were collected from 83 glioma patients at different stages and 69 healthy
      controls. RNA was extracted and the relative expression of serum miR-29 was
      acquired by qRT-PCR and calculated by Cycle threshold (Ct) with microRNA-24 as an
      internal control. In the meta-analysis, studies concerning the predictive value
      of miR-29 family in cancer were retrieved. The predictive value of serum miR-29
      family for glioma was moderate (AUC = 0.74). But the predictive value of serum
      miR-29 family in high-graded glioma detection was sufficient (AUC = 0.81). Also,
      serum miR-29 family might not be applicable in early-stage glioma detection (AUC
      = 0.66). A high predictive value of miR-29 family in multi-cancer detection was
      observed from meta-analysis (AUC = 0.83). This study manifested that serum miR-29
      family could be applied as a biomarker for high-graded glioma screening, but the
      sensitivity and specificity for low-graded glioma detection might not be
      sufficient. A meta-analysis concerning the predictive value of miR-29 family in
      multi-cancer detection concluded that miR-29 family might be a sufficient
      universal biomarker for cancer.

PMID- 25367877
TI  - Lead Intoxication Synergies of the Ethanol-Induced Toxic Responses in Neuronal
      Cells--PC12.
AB  - Lead (Pb)-induced neurodegeneration and its link with widespread neurobehavioral
      changes are well documented. Experimental evidences suggest that ethanol could
      enhance the absorption of metals in the body, and alcohol consumption may
      increase the susceptibility to metal intoxication in the brain. However, the
      underlying mechanism of ethanol action in affecting metal toxicity in brain cells
      is poorly understood. Thus, an attempt was made to investigate the modulatory
      effect of ethanol on Pb intoxication in PC12 cells, a rat pheochromocytoma. Cells
      were co-exposed to biological safe doses of Pb (10 MUM) and ethanol (200 mM), and
      data were compared to the response of cells which received independent exposure
      to these chemicals at similar doses. Ethanol (200 mM) exposure significantly
      aggravated the Pb-induced alterations in the end points associated with oxidative
      stress and apoptosis. The finding confirms the involvement of reactive oxygen
      species (ROS)-mediated oxidative stress, and impairment of mitochondrial membrane
      potential, which subsequently facilitate the translocation of triggering proteins
      between cytoplasm and mitochondria. We further confirmed the apoptotic changes
      due to induction of mitochondria-mediated caspase cascade. These cellular changes
      were found to recover significantly, if the cells are exposed to N-acetyl
      cysteine (NAC), a known antioxidant. Our data suggest that ethanol may potentiate
      Pb-induced cellular damage in brain cells, but such damaging effects could be
      recovered by inhibition of ROS generation. These results open up further
      possibilities for the design of new therapeutics based on antioxidants to prevent
      neurodegeneration and associated health problems.

PMID- 25367879
TI  - Possible Role of Raf-1 Kinase in the Development of Cerebral Vasospasm and Early
      Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.
AB  - This study aims to clarify the potential role of Raf-1 kinase in cerebral
      vasospasm (CVS) and early brain injury (EBI) after subarachnoid hemorrhage (SAH).
      Two experimental SAH models in rats, including cisterna magna double injection
      model for CVS study and prechiasmatic cistern single injection model for EBI
      study, were performed in this research. As a specific inhibitor of Raf-1, BAY 43
      9006 was used in this study. In CVS study, time course study showed that the
      basilar artery exhibited vasospasm after SAH and became most severe at day 5, and
      the phosphorylation of Raf-1 had the same trends, while both vasospasm and the
      phosphorylation of Raf-1 induced by SAH were inhibited by BAY 43-9006 treatment.
      In addition, BAY 43-9006 treatment significantly reversed the phosphorylation of
      ERK1/2 and the activation of NF-kappaB induced by SAH and decreased the messenger
      RNA (mRNA) levels of IL-6 and IL-1beta. In EBI study, BAY 43-9006 treatment
      significantly suppressed the brain injury induced by SAH. Besides, BAY 43-9006
      inhibited the phosphorylation of Raf-1 and ERK1/2; decreased the protein levels
      of COX-2, VEGF, and MMP-9; and reversed the activation of NF-kappaB induced by
      SAH. These results demonstrate that Raf-1 kinase contributes to CVS and EBI after
      SAH by enhancing the activation of the Raf-1/ERK1/2 and Raf-1/NF-kappaB signaling
      pathways, and that the inhibition of these pathways might offer new treatment
      strategies for CVS and EBI. 

PMID- 25367880
TI  - Circulating MicroRNA as Potential Source for Neurodegenerative Diseases
      Biomarkers.
AB  - An increasing number of circulating micro-ribonucleic acids (microRNAs, miRNAs)
      have been discovered its potential as biomarkers to diagnose neurodegenerative
      diseases (NDs) by many researchers. However, there were obvious inconsistencies
      among previous studies, and thus we performed this meta-analysis to evaluate
      whether miRNA is an effective biomarker with high accuracy to diagnose the NDs.
      PubMed, MEDLINE, EMBASE, the Cochrane Library, and other related databases were
      used to search eligible articles. The data of sensitivity and specificity were
      employed to plot the summary receiver operator characteristic (SROC) curve and
      calculate the area under the SROC curve (AUC). I (2) test were used to estimate
      the heterogeneity among different studies. In addition, the possible sources of
      heterogeneity were further explored by subgroup analyses and meta-regression. All
      analyses were performed by STATA 12.0 software. In this meta-analysis, eight
      publications with 459 NDs patients and 340 healthy controls were included to
      investigate the diagnostic performance of circulating miRNAs for NDs. The overall
      sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood
      ration (NLR), and diagnostic odds ratio (DOR) were 0.83 (95% confidence interval
      (CI) 0.77-0.88), 0.87 (95% CI 0.83-0.89), 6.2 (95% CI 4.9-7.9), 0.19 (95% CI 0.14
      0.27), 33 (95% CI 20-52), and 0.91 (95% CI: 0.88-0.93), respectively. The overall
      SROC curve was plotted with AUC of 0.91 (95% CI 0.88-0.93), which indicated an
      excellent diagnostic performance of circulating miRNA for NDs. Subgroup analysis
      based on miRNA profile demonstrated that multiple-miRNA assay had higher
      diagnostic accuracy for NDs when compared with single-miRNA assay. In conclusion,
      the circulating miRNAs may be the potential biomarkers in the clinical diagnosis
      of NDs, and the diagnostic accuracy would be better by using multiple-miRNA
      assay. However, large-scale studies are still needed to explore the relation
      between the circulating miRNA dysregulation and the pathological mechanism of
      NDs.

PMID- 25367882
TI  - Senegenin Inhibits Hypoxia/Reoxygenation-Induced Neuronal Apoptosis by
      Upregulating RhoGDIalpha.
AB  - Neuronal apoptosis is an important event in hypoxia/reoxygenation (H/R)-induced
      neuronal injury. Senegenin (Sen), the predominant and most active component in
      Radix Polygalae root extracts, displays anti-apoptotic and anti-oxidative
      properties. Sen protects against H/R-induced neuronal apoptosis of highly
      differentiated PC12 cells and primary cortical neurons. Sen has also been
      investigated as a source of potential therapeutic targets. In this study, a
      proteomic approach was used to identify Sen-regulated proteins in PC12 cells. We
      found that Sen protected against H/R-induced neuronal apoptosis by upregulating
      RhoGDIalpha protein expression. The regulatory functions of RhoGDIalpha were
      investigated by knocking down RhoGDIalpha expression in PC12 cells using small
      interfering RNA (siRNA), followed by quantification of apoptosis and then
      altering the expression levels of apoptosis-related proteins. Our data show that
      after silencing RhoGDIalpha, the neuroprotective effects of Sen on H/R-induced
      PC12 cell apoptosis were absent. Furthermore, RhoGDIalpha silencing alleviated
      the Sen-mediated inhibition of the JNK pathway. Therefore, these findings
      indicated that Sen attenuates H/R-induced neuronal apoptosis by upregulating
      RhoGDIalpha expression and inhibiting the JNK pathway. In addition to the
      mechanism underlying neuroprotective effects of Sen, RhoGDIalpha was identified
      as a putative target of Sen based on a primary rat cortical neuron model of H/R
      induced injury. 

PMID- 25367881
TI  - Corilagin Protects Against HSV1 Encephalitis Through Inhibiting the TLR2
      Signaling Pathways In Vivo and In Vitro.
AB  - In this study, we tried to explore the molecular mechanism that Corilagin
      protected against herpes simplex virus-1 encephalitis through inhibiting the TLR2
      signaling pathways in vivo and in vitro. As a result, Corilagin significantly
      prevented increase in the levels of TLR2 and its downstream mediators following
      Malp2 or HSV-1 challenge. On the other hand, in spite of TLR2 knockdown,
      Corilagin could still significantly suppress the expression of P38 and NEMO,
      phosphor-P38, and nuclear factor kappa B. The mRNA and protein expression of TLR2
      and its downstream mediators in the brain tissue were also significantly lowered
      in mice treated with Corilagin. In addition, Corilagin inhibited expression of
      tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 protein. In
      conclusion, Corilagin shows the potential to protect against HSV-1-induced
      encephalitis, and the beneficial effects may be mediated by inhibiting TLR2
      signaling pathways. 

PMID- 25367883
TI  - Hemorrhagic Transformation after Tissue Plasminogen Activator Reperfusion Therapy
      for Ischemic Stroke: Mechanisms, Models, and Biomarkers.
AB  - Intracerebral hemorrhagic transformation (HT) is well recognized as a common
      cause of hemorrhage in patients with ischemic stroke. HT after acute ischemic
      stroke contributes to early mortality and adversely affects functional recovery.
      The risk of HT is especially high when patients receive thrombolytic reperfusion
      therapy with tissue plasminogen activator, the only available treatment for
      ischemic stroke. Although many important publications address preclinical models
      of ischemic stroke, there are no current recommendations regarding the conduct of
      research aimed at understanding the mechanisms and prediction of HT. In this
      review, we discuss the underlying mechanisms for HT after ischemic stroke,
      provide an overview of the models commonly used for the study of HT, and discuss
      biomarkers that might be used for the early detection of this challenging
      clinical problem. 

PMID- 25367884
TI  - Activation of Glycogen Synthase Kinase-3 Mediates the Olfactory Deficit-Induced
      Hippocampal Impairments.
AB  - The populations with olfactory dysfunction show an increased chance for
      hippocampus-dependent episodic memory deficit. Although it is known that the
      olfactory information projects to the hippocampus through entorhinal cortex layer
      II, the molecular mechanisms linking olfactory deficit to the hippocampus is not
      understood. Using bilateral olfactory bulbectomy (OBX) as a model, we found that
      OBX induced memory deficits with activation of several memory-related protein
      kinases in the hippocampal extracts, including glycogen synthase kinase-3beta
      (GSK-3beta), protein kinase A (PKA), extracellular-signal-regulated kinase (ERK),
      c-Jun N-terminal kinase (JNK), phosphatidylinositol-3-kinase (PI3K), and protein
      kinase B (PKB). The OBX rats also show suppression of long-term potentiation
      (LTP); reduction of synapsin I, synaptophysin, NR2A/B, and PSD95; thinner
      presynaptic active zone and postsynaptic density with enlarged synaptic space;
      decreased spine numbers and mushroom-type spines; and tau hyperphosphorylation.
      After injection of SB216763 for several weeks by vena caudalis, selective
      inhibition of GSK-3beta ameliorated the OBX-induced memory deficits with recovery
      of the synaptic components and tau phosphorylation. Furthermore, genetic ablation
      of GSK-3beta by lentivirus-packed shRNA effectively rescued the memory deficits,
      synaptic disorder, and tauopathy. Our data indicate that GSK-3 activation
      mediates the olfactory deficits to the hippocampus, and targeting GSK-3 blocks
      the pathological connection. 

PMID- 25367885
TI  - Nuclear Protein C23 on the Cell Surface Plays an Important Role in Activation of
      CXCR4 Signaling in Glioblastoma.
AB  - The chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 (SDF-1)
      plays an important role in tumor progression and are associated with
      angiogenesis. Meanwhile, the implications of C23 in multiple signaling pathways
      have been also investigated. However, the effects of C23 on CXCR4 pathway in
      glioblastoma are not fully characterized. In the present study, C23 and CXCR4 of
      U87 cell line were inhibited by anti-C23 and anti-CXCR4 antibodies, respectively;
      and then C23 and CXCR4 siRNAs were used to knock down endogenous C23 and CXCR4,
      respectively. In addition, MTT assay was also introduced. Our data showed that
      either anti-C23 or anti-CXCR4 antibodies efficaciously repressed the
      phosphorylation levels of ERK (p < 0.000) and AKT (p < 0.000) compared with SDF-1
      alone and control. As expected, either C23 or CXCR4 siRNAs indeed resulted in C23
      and CXCR4 knockdown and further suppressed the expression of p-ERK and p-AKT.
      Most importantly, immunoprecipitation revealed C23 interacted with CXCR4 once U87
      was exposed to SDF-1 treatment. In addition, MTT assay identified that C23 or
      CXCR4 siRNAs could obviously decreased cell proliferation capacity (p = 0.002).
      In conclusion, our results suggest that C23 plays a crucial role in activation of
      SDF-1-induced ERK and PI3K/AKT pathways via interacting with CXCR4. Furthermore,
      C23 could be recommended as an important element in glioblastoma development and
      a new target for glioblastoma treatment.

PMID- 25367886
TI  - Vitamin C Attenuates Isoflurane-Induced Caspase-3 Activation and Cognitive
      Impairment.
AB  - Anesthetic isoflurane has been reported to induce caspase-3 activation. The
      underlying mechanism(s) and targeted intervention(s), however, remain largely to
      be determined. Vitamin C (VitC) inhibits oxidative stress and apoptosis. We
      therefore employed VitC to further determine the up-stream mechanisms and the
      down-stream consequences of the isoflurane-induced caspase-3 activation. H4 human
      neuroglioma cells overexpressed human amyloid precursor protein (H4-APP cells)
      and rat neuroblastoma cells were treated either with (1) 2% isoflurane or (2)
      with the control condition, plus saline or 400 MUM VitC for 3 or 6 h. Western
      blot analysis and fluorescence assay were utilized at the end of the experiments
      to determine caspase-3 activation, levels of reactive oxygen species and ATP, and
      mitochondrial function. The interaction of isoflurane (1.4% for 2 h) and VitC
      (100 mg/kg) on cognitive function in mice was also assessed in the fear
      conditioning system. Here, we show for the first time that the VitC treatment
      attenuated the isoflurane-induced caspase-3 activation. Moreover, VitC mitigated
      the isoflurane-induced increases in the levels of reactive oxygen species,
      opening of mitochondrial permeability transition pore, reduction in mitochondrial
      membrane potential, and the reduction in ATP levels in the cells. Finally, VitC
      ameliorated the isoflurane-induced cognitive impairment in the mice. Pending
      confirmation from future studies, these results suggested that VitC attenuated
      the isoflurane-induced caspase-3 activation and cognitive impairment by
      inhibiting the isoflurane-induced oxidative stress, mitochondrial dysfunction,
      and reduction in ATP levels. These findings would promote further research into
      the underlying mechanisms and targeted interventions of anesthesia neurotoxicity.

PMID- 25367888
TI  - Melanoma incidence increases in the elderly of Catalonia but not in the younger
      population: effect of prevention or consequence of immigration?
AB  - All cases of MM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007 were
      recorded and melanoma incidence calculated and adjusted for the European standard
      population via the direct method. The age standardised rate/100,000 inhabitants
      varied from 6.74 in 2000 to 8.64 in 2007 for all melanomas and from 4.79 to 5.80
      for invasive MMs; the Breslow thickness was stable during the period. The
      increase in invasive melanoma incidence in the elderly was remarkable, the crude
      rate/100,000 inhabitants increasing from 11.04 (2000) to 15.49 (2007) in the 60
      64 year population, while remaining more stable in the 30-34 year range, from
      3.97 in 2000 to 4.55 in 2007, and with a tendency to decrease from 5.1 in 2000 to
      2.5 in 2007 for the age range of 25-29 years. These lower age ranges are much
      more affected by immigration. Despite the large immigrant population (nearly one
      million immigrants arrived in Catalonia during the study period from countries
      with a low melanoma incidence), melanoma incidence in our region has risen
      considerably and this trend is likely to persist in the near future.

PMID- 25367887
TI  - Experimental Lung Injury Promotes Changes in Oxidative/Nitrative Status and
      Inflammatory Markers in Cerebral Cortex of Rats.
AB  - In the present study, we investigate the effect of lung injury on parameters of
      oxidative/nitrative stress [reactive oxygen species production, nitrite levels,
      thiobarbituric acid-reactive substances (TBARS), carbonyl content, sulfhydryl
      content, activities of antioxidant enzymes (superoxide dismutase, catalase, and
      glutathione peroxidase), total radical-trapping antioxidant potential,
      glutathione content, and glucose-6-phosphate dehydrogenase], as well as on
      inflammation mediators [immunocontent of nuclear factor-kappaB (NF-kappaB) total
      (p65), NF-kappaB phosphorylated (pp65) subunit (cytosolic and nuclear), TNF
      alpha, IL-1beta, IL-6, and IL-10] in the cerebral cortex. Cytokine levels in
      serum were also evaluated. Adult Wistar rats were submitted to lung injury
      induced by intratracheal instillation of lipopolysaccharide in a dose of 100
      MUg/100 g body weight. Sham group (control) received isotonic saline
      instillation. Twelve hours after the injury, rats were decapitated and blood
      samples were collected and the cerebral cortex dissected out. Results showed an
      increase in reactive oxygen species production, TBARS, and nitrite and carbonyl
      levels in the cerebral cortex of rats submitted to lung injury. Antioxidant
      enzymatic defenses were altered, superoxide dismutase and glutathione peroxidase
      activities decreased, and catalase activity increased. Non-enzymatic antioxidant
      capacity, glutathione content, and glucose-6-phosphate dehydrogenase were
      decreased. Inflammatory parameters were also altered in the cerebral cortex of
      rats subjected to lung injury; it was observed an increase in the immunocontent
      of NF-kappaB/p65 (nuclear fraction) and NF-kappaB/pp65 (cytosolic and nuclear
      faction), as well as an increase in TNF-alpha, IL-1beta, IL-6, and IL-10 levels.
      The levels of IL-10 also increased in the serum. Our findings show that the lung
      injury alters oxidative/nitrative status and induces inflammation in the cerebral
      cortex of rats, which might be associated with cognitive impairments present in
      patients with lung injury.

PMID- 25367889
TI  - Encapsulation of black carrot juice using spray and freeze drying.
AB  - Black carrot juice extracted using pectinase enzyme was encapsulated in three
      different carrier materials (maltodextrin 20DE, gum arabic and tapioca starch)
      using spray drying at four inlet temperatures (150, 175, 200 and 225 C) and
      freeze drying at a constant temperature of - 53 C and vacuum of 0.22-0.11 mbar
      with the constant feed mixture. The products were analyzed for total anthocyanin
      content, antioxidant activity, water solubility index, encapsulation efficiency
      and total colour change. For both the drying methods followed in this study,
      maltodextrin 20DE as the carrier material has proven to be better in retaining
      maximum anthocyanin and antioxidant activity compared to gum arabic and tapioca
      starch. The best spray dried product, was obtained at 150 C. The most acceptable
      was the freeze dried product with maximum anthocyanin content, antioxidant
      activity, water solubility index, encapsulation efficiency and colour change.

PMID- 25367890
TI  - Acute tier-1 and tier-2 effect assessment approaches in the EFSA Aquatic Guidance
      Document: are they sufficiently protective for insecticides?
AB  - BACKGROUND: The objective of this paper is to evaluate whether the acute tier-1
      and tier-2 methods as proposed by the Aquatic Guidance Document recently
      published by the European Food Safety Authority (EFSA) are appropriate for
      deriving regulatory acceptable concentrations (RACs) for insecticides. The tier-1
      and tier-2 RACs were compared with RACs based on threshold concentrations from
      micro/mesocosm studies (ETO-RAC). A lower-tier RAC was considered as sufficiently
      protective, if less than the corresponding ETO-RAC. RESULTS: ETO-RACs were
      calculated for repeated (n = 13) and/or single pulsed applications (n = 17) of 26
      insecticides to micro/mesocosms, giving a maximum of 30 insecticide * application
      combinations (i.e. cases) for comparison. Acute tier-1 RACs (for 24 insecticides)
      were lower than the corresponding ETO-RACs in 27 out of 29 cases, while tier-2
      Geom-RACs (for 23 insecticides) were lower in 24 out of 26 cases. The tier-2 SSD
      RAC (for 21 insecticides) using HC5 /3 was lower than the ETO-RAC in 23 out of 27
      cases, whereas the tier-2 SSD-RAC using HC5 /6 was protective in 25 out of 27
      cases. CONCLUSION: The tier-1 and tier-2 approaches proposed by EFSA for acute
      effect assessment are sufficiently protective for the majority of insecticides
      evaluated. Further evaluation may be needed for insecticides with more novel
      chemistries (neonicotinoids, biopesticides) and compounds that show delayed
      effects (insect growth regulators).

PMID- 25367891
TI  - Coiled coil driven membrane fusion between cyclodextrin vesicles and liposomes.
AB  - Controlled fusion events between natural membranes composed of phospholipids with
      synthetic unnatural membranes will yield valuable fundamental information on the
      mechanism of membrane fusion. Here, fusion between vastly different phospholipid
      liposomes and cyclodextrin amphiphile based vesicles (CDVs) controlled by a pair
      of coiled coil forming lipidated peptides was investigated. Fusion events were
      characterized using lipid and content mixing assays and the resulting hybrid
      assemblies were characterized with cryo-TEM imaging. The secondary/quaternary
      structure of the lipidated peptides at the membrane interface was studied using
      circular dichroism spectroscopy. This is the first example of targeted fusion
      between natural and non-natural bilayer membranes and the in situ formation of
      hybrid CDV-liposome structures is of interest as it yields fundamental
      information about the mechanism through which fusion proceeds. 

PMID- 25367892
TI  - Direct vs. indirect pathway for nitrobenzene reduction reaction on a Ni catalyst
      surface: a density functional study.
AB  - Density functional theory (DFT) calculations are performed to understand and
      address the previous experimental results that showed the reduction of
      nitrobenzene to aniline prefers direct over indirect reaction pathways
      irrespective of the catalyst surface. Nitrobenzene to aniline conversion occurs
      via the hydroxyl amine intermediate (direct pathway) or via the azoxybenzene
      intermediate (indirect pathway). Through our computational study we calculated
      the spin polarized and dispersion corrected reaction energies and activation
      barriers corresponding to various reaction pathways for the reduction of
      nitrobenzene to aniline over a Ni catalyst surface. The adsorption behaviour of
      the substrate, nitrobenzene, on the catalyst surface was also considered and the
      energetically most preferable structural orientation was elucidated. Our study
      indicates that the parallel adsorption behaviour of the molecules over a catalyst
      surface is preferable over vertical adsorption behaviour. Based on the reaction
      energies and activation barrier of the various elementary steps involved in
      direct or indirect reaction pathways, we find that the direct reduction pathway
      of nitrobenzene over the Ni(111) catalyst surface is more favourable than the
      indirect reaction pathway. 

PMID- 25367893
TI  - Evaluation of quantification methods for left arial late gadolinium enhancement
      based on different references in patients with atrial fibrillation.
AB  - By using late gadolinium enhancement cardiac magnetic resonance (LGE-CMR)
      imaging, we compared left atrial late gadolinium enhancement (LA-LGE)
      quantification methods based on different references to characterize the left
      atrial wall in patients with atrial fibrillation (AF). Thirty-eight patients who
      underwent three-dimensional LGE-CMR imaging before catheter ablation for AF were
      classified into three groups depending on their clinical AF type: (1) paroxysmal
      AF (PAF; n = 12); (2) persistent AF (PeAF; n = 16); and (3) recurrent AF after
      catheter ablation (RAF; n = 10). To quantify LA-LGE on LGE-CMR imaging, we used
      the thresholds of 2 standard deviations (2-SD), 3-SD, 4-SD, 5-SD, or 6-SD above
      the mean signal from the unenhanced left ventricular myocardium, and we used the
      full width at half maximum (FWHM) technique, which was based on the maximum
      signal from the mitral valve with high signal intensity. The 6-SD threshold and
      FWHM techniques were statistically reproducible with an intraclass correlation
      coefficient >0.7. On applying the FWHM technique, the normalized LA-LGE volume by
      LA wall area showed a significant difference between the RAF, PeAF, and PAF
      groups (0.22 +/- 0.04, 0.16 +/- 0.06, and 0.09 +/- 0.03 mL/cm(2), respectively)
      (P < 0.05). Furthermore, most of the fibrotic scarring and low-voltage tissue on
      the electroanatomic map corresponded well with the extent of LA-LGE. The FWHM
      technique based on the mitral valve can provide a reproducible quantification of
      LA-LGE related to AF in the thin LA wall.

PMID- 25367894
TI  - Ordered nanoparticle arrays interconnected by molecular linkers: electronic and
      optoelectronic properties.
AB  - Arrays of metal nanoparticles in an organic matrix have attracted a lot of
      interest due to their diverse electronic and optoelectronic properties. Recent
      work demonstrates that nanoparticle arrays can be utilized as a template
      structure to incorporate single molecules. In this arrangement, the nanoparticles
      act as electronic contacts to the molecules. By varying parameters such as the
      nanoparticle material, the matrix material, the nanoparticle size, and the
      interparticle distance, the electronic behavior of the nanoparticle arrays can be
      substantially tuned and controlled. Furthermore, via the excitation of surface
      plasmon polaritons, the nanoparticles can be optically excited and electronically
      read-out. The versatility and possible applications of well-ordered nanoparticle
      arrays has been demonstrated by the realization of switching devices triggered
      optically or chemically and by the demonstration of chemical and mechanical
      sensing. Interestingly, hexagonal nanoparticle arrays may also become a useful
      platform to study the physics of collective plasmon resonances that can be
      described as Dirac-like bosonic excitations. 

PMID- 25367895
TI  - Between hope and evidence: how community advisors demarcate the boundary between
      legitimate and illegitimate stem cell treatments.
AB  - Stem cell science provides an exemplary study of the 'management of hope'. On the
      one hand, raising 'hopes' and expectations is a seen as a necessary aspect of
      securing investment in promising innovative research. On the other, such
      hyperbole risks raising hopes to a level that may lead people to undertake undue
      risks, which may ultimately undermine confidence in medical research. In this
      context, the 'management of hope' thus involves the negotiation of competing
      claims of truth about the value and safety of particular treatments and about the
      trustworthiness of providers. Using Gieryn's concept of boundary-work, this
      article examines the means by which this work of 'managing hope' is undertaken.
      Drawing on data collected as part of our study that investigated the perspectives
      of those who are consulted by patients and their carers about stem cell
      treatments, we explore how these community advisors - both scientists and
      clinicians with a stake in stem cell research and representatives from patient
      advocacy groups - demarcate the boundary between legitimate and illegitimate
      treatments. In particular, we examine how these actors rhetorically use
      'evidence' to achieve this demarcation. We argue that analysing accounts of how
      advisors respond to patient enquiries about stem cell treatments offers a window
      for examining the workings of the politics of hope within contemporary bioscience
      and biomedicine. In conclusion, we emphasize the need to re-conceptualize the
      boundary between science and non-science so as to allow a better appreciation of
      the realities of health care in the age of medical travel.

PMID- 25367896
TI  - Creating a Novel Video Vignette Stroke Preparedness Outcome Measure Using a
      Community-Based Participatory Approach.
AB  - Evaluating the efficacy of behavioral interventions for rare outcomes is a
      challenge. One such topic is stroke preparedness, defined as inteventions to
      increase stroke symptom recognition and behavioral intent to call 911. Current
      stroke preparedness intermediate outcome measures are centered on written
      vignettes or open-ended questions and have been shown to poorly reflect actual
      behavior. Given that stroke identification and action requires aural and visual
      processing, video vignettes may improve on current measures. This article
      discusses an approach for creating a novel stroke preparedness video vignette
      intermediate outcome measure within a community-based participatory research
      partnership. A total of 20 video vignettes were filmed of which 13 were
      unambiguous (stroke or not stroke) as determined by stroke experts and had test
      discrimination among community participants. Acceptable reliability, high
      satisfaction, and cultural relevance were found among the 14 community
      respondents. A community-based participatory approach was effective in creating a
      video vignette intermediate outcome. Future projects should consider obtaining
      expert and community feedback prior to filming all the video vignettes to improve
      the proportion of vignettes that are usable. While content validity and
      preliminary reliability were established, future studies are needed to confirm
      the reliability and establish construct validity. 

PMID- 25367897
TI  - Attitudes of patients with bipolar disorder toward the Life Chart Methodology: a
      phenomenological study.
AB  - BACKGROUND: The Dutch guideline for bipolar disorder (BD) recommends the use of
      the Life Chart Methodology (LCM) to help patients to monitor fluctuating mood
      patterns. But in practice patients show ambivalent attitudes toward this
      instrument. OBJECTIVE: To describe attitudes and motivations of patients with BD
      for (non-)using the LCM. DESIGN: A phenomenological study with unstructured in
      depth interviews of 14 patients with BD. Patient narratives were audio-taped,
      transcribed verbatim, analyzed, and coded inductively. RESULTS: The results show
      that despite variability in perceptions and willingness to work with the LCM, the
      general attitude toward this instrument was a recognized value for using the LCM.
      However, the emotional impact of daily mood charting was experienced as a
      substantial burden, particularly during the early stages of diagnosis.
      CONCLUSION: The impact of the diagnosis of BD needs to be taken in account when
      introducing the instrument for the first time to a patient.

PMID- 25367898
TI  - Adrenal clocks and the role of adrenal hormones in the regulation of circadian
      physiology.
AB  - The mammalian circadian timing system consists of a master pacemaker in the
      suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time
      information to various central and peripheral tissues. While the function of the
      SCN in circadian rhythm regulation has been extensively studied, we still have
      limited understanding of how peripheral tissue clock function contributes to the
      regulation of physiological processes. The adrenal gland plays a special role in
      this context as adrenal hormones show strong circadian secretion rhythms
      affecting downstream physiological processes. At the same time, they have been
      shown to affect clock gene expression in various other tissues, thus mediating
      systemic entrainment to external zeitgebers and promoting internal circadian
      alignment. In this review, we discuss the function of circadian clocks in the
      adrenal gland, how they are reset by the SCN and may further relay time-of-day
      information to other tissues. Focusing on glucocorticoids, we conclude by
      outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic,
      immune, and malignant disorders. 

PMID- 25367899
TI  - Circadian clock function in the mammalian ovary.
AB  - Rhythmic events in the female reproductive system depend on the coordinated and
      synchronized activity of multiple neuroendocrine and endocrine tissues. This
      coordination is facilitated by the timing of gene expression and cellular
      physiology at each level of the hypothalamo-pituitary-ovarian (HPO) axis,
      including the basal hypothalamus and forebrain, the pituitary gland, and the
      ovary. Central to this pathway is the primary circadian pacemaker in the
      suprachiasmatic nucleus (SCN) that, through its myriad outputs, provides a
      temporal framework for gonadotropin release and ovulation. The heart of the
      timing system, a transcription-based oscillator, imparts SCN pacemaker cells and
      a company of peripheral tissues with the capacity for daily oscillations of gene
      expression and cellular physiology. Although the SCN sits comfortably at the
      helm, peripheral oscillators (such as the ovary) have undefined but potentially
      critical roles. Each cell type of the ovary, including theca cells, granulosa
      cells, and oocytes, harbor a molecular clock implicated in the processes of
      follicular growth, steroid hormone synthesis, and ovulation. The ovarian clock is
      influenced by the reproductive cycle and diseases that perturb the cycle and/or
      follicular growth can disrupt the timing of clock gene expression in the ovary.
      Chronodisruption is known to negatively affect reproductive function and
      fertility in both rodent models and women exposed to shiftwork schedules. Thus,
      influencing clock function in the HPO axis with chronobiotics may represent a
      novel avenue for the treatment of common fertility disorders, particularly those
      resulting from chronic circadian disruption. 

PMID- 25367900
TI  - A new system for profiling drug-induced calcium signal perturbation in human
      embryonic stem cell-derived cardiomyocytes.
AB  - The emergence of human stem cell-derived cardiomyocyte (hSCCM)-based assays in
      the cardiovascular (CV) drug discovery sphere requires the development of
      improved systems for interrogating the rich information that these cell models
      have the potential to yield. We developed a new analytical framework termed SALVO
      (synchronization, amplitude, length, and variability of oscillation) to profile
      the amplitude and temporal patterning of intra- and intercellular calcium signals
      in hSCCM. SALVO quantified drug-induced perturbations in the calcium signaling
      "fingerprint" in spontaneously contractile hSCCM. Multiparametric SALVO outputs
      were integrated into a single index of in vitro cytotoxicity that confirmed the
      rank order of perturbation as astemizole > thioridazine > cisapride > flecainide
      > valdecoxib > sotalol > nadolol ~ control. This rank order of drug-induced
      Ca(2+) signal disruption is in close agreement with the known arrhythmogenic
      liabilities of these compounds in humans. Validation of the system using a second
      set of compounds and hierarchical cluster analysis demonstrated the utility of
      SALVO to discriminate drugs based on their mechanisms of action. We discuss the
      utility of this new mechanistically agnostic system for the evaluation of in
      vitro drug cytotoxicity in hSCCM syncytia and the potential placement of SALVO in
      the early stage drug screening framework. 

PMID- 25367901
TI  - Detection of single-nucleotide polymorphisms in Plasmodium falciparum by PCR
      primer extension and lateral flow immunoassay.
AB  - The resistance of Plasmodium falciparum to some antimalarial drugs is linked to
      single-nucleotide polymorphisms (SNPs). Currently, there are no methods for the
      identification of resistant parasites that are sufficiently simple, cheap, and
      fast enough to be performed at point-of-care, i.e., in local hospitals where
      drugs are prescribed. Primer extension methods (PEXT) were developed to identify
      4 SNPs in P. falciparum positioned at amino acids 86, 184, and 1246 of the P.
      falciparum multidrug resistance 1 gene (pfmdr1) and amino acid 76 of the
      chloroquine resistance transporter gene (pfcrt). The PEXT products were
      visualized by a nucleic acid lateral flow immunoassay (NALFIA) with carbon
      nanoparticles as the detection labels. PCR-PEXT-NALFIAs showed good correlation
      to the reference methods, quantitative PCR (qPCR) or direct amplicon sequence
      analysis, in an initial open-label evaluation with 17 field samples. The tests
      were further evaluated in a blind study design in a set of 150 patient isolates.
      High specificities of 98 to 100% were found for all 4 PCR-PEXT genotyping assays.
      The sensitivities ranged from 75% to 100% when all PEXT-positive tests were
      considered. A number of samples with a low parasite density were successfully
      characterized by the reference methods but failed to generate a result in the PCR
      PEXT-NALFIA, particularly those samples with microscopy-negative subpatent
      infections. This proof-of principle study validates the use of PCR-PEXT-NALFIA
      for the detection of resistance-associated mutations in P. falciparum,
      particularly for microscopy-positive infections. Although it requires a standard
      thermal cycler, the procedure is cheap and rapid and thus a potentially valuable
      tool for point-of-care detection in developing countries. 

PMID- 25367902
TI  - First report of a clinical, multidrug-resistant Enterobacteriaceae isolate
      coharboring fosfomycin resistance gene fosA3 and carbapenemase gene blaKPC-2 on
      the same transposon, Tn1721.
AB  - In order to understand the genetic background and dissemination mechanism of
      carbapenem resistance and fosfomycin resistance in Enterobacteriaceae isolates,
      we studied a clinical Escherichia coli strain HS102707 isolate and an
      Enterobacter aerogenes strain HS112625 isolate, both of which were resistant to
      carbapenem and fosfomycin and positive for the bla(KPC-2) and fosA3 genes. In
      addition, a clinical Klebsiella pneumoniae strain HS092839 isolate which was
      resistant to carbapenem was also studied. A 70-kb plasmid was successfully
      transferred to recipient E. coli J53 by a conjugation test. PCR and Southern blot
      analysis showed that bla(KPC-2) was located on this plasmid. The complete
      sequence of pHS102707 showed that this plasmid belongs to the P11 subfamily
      (IncP1) and has a replication gene, several plasmid-stable genes, an intact type
      IV secretion system gene cluster, and a composite transposon Tn1721-Tn3 that
      harbored bla(KPC-2). Interestingly, a composite IS26 transposon carrying fosA3
      was inserted in the Tn1721-tnpA gene in pHS102707 and pHS112625, leading to the
      disruption of Tn1721-tnpA and the deletion of Tn1721-tnpR. However, only IS26
      with a truncated Tn21-tnpR was inserted in pHS092839 at the same position. To our
      knowledge, this is the first report of fosA3 and bla(KPC-2) colocated in the same
      Tn1721-Tn3-like composite transposon on a novel IncP group plasmid.

PMID- 25367903
TI  - Identification of TEM-135 beta-lactamase in Neisseria gonorrhoeae strains
      carrying African and Toronto plasmids in Argentina.
AB  - One hundred forty-three penicillinase-producing Neisseria gonorrhoeae (PPNG)
      isolates obtained in Argentina from 2008 and 2012 were examined to detect blaTEM
      135 genes and to investigate plasmid profiles and multiantigen sequence types.
      Forty-two PPNG isolates were found to carry TEM-135, and two contained a new TEM
      derivative characterized as TEM-220. The blaTEM-135 allele was carried by the
      Toronto/Rio and African plasmids. Molecular epidemiology revealed that two blaTEM
      135 isolates were related to previously described isolates from Thailand and
      China, indicating a common evolutionary origin. 

PMID- 25367904
TI  - Pharmacokinetic-pharmacodynamic analysis for efficacy of ceftaroline fosamil in
      patients with acute bacterial skin and skin structure infections.
AB  - Ceftaroline is a cephalosporin with broad-spectrum in vitro activity against
      pathogens commonly associated with acute bacterial skin and skin structure
      infections (ABSSSI), including methicillin-resistant Staphylococcus aureus.
      Ceftaroline fosamil, the prodrug of ceftaroline, is approved for the treatment of
      patients with ABSSSI. Using data from the microbiologically evaluable population
      from two phase 2 and two phase 3 randomized, multicenter, double-blind studies of
      patients with ABSSSI, an analysis examining the relationship between drug
      exposure, as measured by the percentage of time during the dosing interval that
      free-drug steady-state concentrations remain above the MIC (f%T>MIC), and
      clinical and microbiological responses was undertaken. The analysis population
      included 526 patients, of whom 423 had infections associated with S. aureus.
      Clinical and microbiological success percentages were 94.7 and 94.5%,
      respectively, among all of the patients and 95.3 and 95.7%, respectively, among
      those with S. aureus infections. Univariable analysis based on data from all of
      the patients and those with S. aureus infections demonstrated significant
      relationships between f%T>MIC and microbiological response (P < 0.001 and P =
      0.026, respectively). Multivariable logistic regression analyses demonstrated
      other patient factors in addition to f%T>MIC to be significant predictors of
      microbiological response, including age and infection type for all of the
      patients evaluated and age, infection type, and the presence of diabetes mellitus
      for patients with S. aureus infections. Results of these analyses confirm that a
      ceftaroline fosamil dosing regimen of 600 mg every 12 h provides exposures
      associated with the upper plateau of the pharmacokinetic-pharmacodynamic
      relationship for efficacy. 

PMID- 25367905
TI  - Novel rate-area-shape modeling approach to quantify bacterial killing and
      regrowth for in vitro static time-kill studies.
AB  - In vitro static concentration time-kill (SCTK) studies are a cornerstone for
      antibiotic development and designing dosage regimens. However, mathematical
      approaches to efficiently model SCTK curves are scarce. The currently used model
      free, descriptive metrics include the log10 change in CFU from 0 h to a defined
      time and the area under the viable count versus time curve. These metrics have
      significant limitations, as they do not characterize the rates of bacterial
      killing and regrowth and lack sensitivity. Our aims were to develop a novel rate
      area-shape modeling approach and to compare, against model-free metrics, its
      relative ability to characterize the rate, extent, and timing of bacterial
      killing and regrowth from SCTK studies. The rate-area-shape model and the model
      free metrics were applied to data for colistin and doripenem against six
      Acinetobacter baumannii strains. Both approaches identified exposure-response
      relationships from 0.5- to 64-fold the MIC. The model-based approach estimated an
      at least 10-fold faster killing by colistin than by doripenem at all multiples of
      the MIC. However, bacterial regrowth was more extensive (by 2 log10) and occurred
      approximately 3 h earlier for colistin than for doripenem. The model-free metrics
      could not consistently differentiate the rate and extent of killing between
      colistin and doripenem. The time to 2 log10 killing was substantially faster for
      colistin. The rate-area-shape model was successfully implemented in Excel. This
      new model provides an improved framework to distinguish between antibiotics with
      different rates of bacterial killing and regrowth and will enable researchers to
      better characterize SCTK experiments and design subsequent dynamic studies. 

PMID- 25367906
TI  - A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitor
      targeting MEP isoprenoid precursor biosynthesis.
AB  - The apicoplast is an essential plastid organelle found in Plasmodium parasites
      which contains several clinically validated antimalarial-drug targets. A chemical
      rescue screen identified MMV-08138 from the "Malaria Box" library of growth
      inhibitory antimalarial compounds as having specific activity against the
      apicoplast. MMV-08138 inhibition of blood-stage Plasmodium falciparum growth is
      stereospecific and potent, with the most active diastereomer demonstrating a 50%
      effective concentration (EC50) of 110 nM. Whole-genome sequencing of 3 drug
      resistant parasite populations from two independent selections revealed E688Q and
      L244I mutations in P. falciparum IspD, an enzyme in the MEP (methyl-d-erythritol
      4-phosphate) isoprenoid precursor biosynthesis pathway in the apicoplast. The
      active diastereomer of MMV-08138 directly inhibited PfIspD activity in vitro with
      a 50% inhibitory concentration (IC50) of 7.0 nM. MMV-08138 is the first PfIspD
      inhibitor to be identified and, together with heterologously expressed PfIspD,
      provides the foundation for further development of this promising antimalarial
      drug candidate lead. Furthermore, this report validates the use of the apicoplast
      chemical rescue screen coupled with target elucidation as a discovery tool to
      identify specific apicoplast-targeting compounds with new mechanisms of action. 

PMID- 25367907
TI  - Cationic liposomal sodium stibogluconate (SSG), a potent therapeutic tool for
      treatment of infection by SSG-sensitive and -resistant Leishmania donovani.
AB  - Pentavalent antimonials have been the first-line treatment for leishmaniasis for
      decades. However, the development of resistance to sodium stibogluconate (SSG)
      has limited its use, especially for treating visceral leishmaniasis (VL). The
      present work aims to optimize a cationic liposomal formulation of SSG for the
      treatment of both SSG-sensitive (AG83) and SSG-resistant (GE1F8R and CK1R)
      Leishmania donovani infections. Parasite killing was determined by the 3-(4,5
      dimethylthiazol-2)-2,5-diphenyltetrazolium bromide (MTT) assay and microscopic
      counting of Giemsa-stained macrophages. Macrophage uptake studies were carried
      out by confocal microscopic imaging. Parasite-liposome interactions were
      visualized through transmission electron microscopy. Toxicity tests were
      performed using assay kits. Organ parasite burdens were determined by microscopic
      counting and limiting dilution assays. Cytokines were measured by enzyme-linked
      immunosorbent assays (ELISAs) and flow cytometry. Although all cationic liposomes
      studied demonstrated leishmanicidal activity, phosphatidylcholine (PC)
      dimethyldioctadecylammonium bromide (DDAB) vesicles were most effective, followed
      by PC-stearylamine (SA) liposomes. Since entrapment of SSG in PC-DDAB liposomes
      demonstrated enhanced ultrastructural alterations in promastigotes, PC-DDAB-SSG
      vesicles were further investigated in vitro and in vivo. PC-DDAB-SSG could
      effectively alleviate SSG-sensitive and SSG-resistant L. donovani infections in
      the liver, spleen, and bone marrow of BALB/c mice at a dose of SSG (3 mg/kg body
      weight) not reported previously. The parasiticidal activity of these vesicles was
      attributed to better interactions with the parasite membranes, resulting in
      direct killing, and generation of a strong host-protective environment,
      necessitating a very low dose of SSG for effective cures. 

PMID- 25367908
TI  - Antiviral characteristics of GSK1265744, an HIV integrase inhibitor dosed orally
      or by long-acting injection.
AB  - GSK1265744 is a new HIV integrase strand transfer inhibitor (INSTI) engineered to
      deliver efficient antiviral activity with a once-daily, low-milligram dose that
      does not require a pharmacokinetic booster. The in vitro antiviral profile and
      mechanism of action of GSK1265744 were established through integrase enzyme
      assays, resistance passage experiments, and cellular assays with site-directed
      molecular (SDM) HIV clones resistant to other classes of anti-HIV-1 agents and
      earlier INSTIs. GSK1265744 inhibited HIV replication with low or subnanomolar
      efficacy and with a selectivity index of at least 22,000 under the same culture
      conditions. The protein-adjusted half-maximal inhibitory concentration (PA-EC50)
      extrapolated to 100% human serum was 102 nM. When the virus was passaged in the
      presence of GSK1265744, highly resistant mutants with more than a 10-fold change
      (FC) in EC50 relative to that of the wild-type were not observed for up to 112
      days of culture. GSK1265744 demonstrated activity against SDM clones containing
      the raltegravir (RAL)-resistant Y143R, Q148K, N155H, and G140S/Q148H signature
      variants (FC less than 6.1), while these mutants had a high FC in the EC50 for
      RAL (11 to >130). Either additive or synergistic effects were observed when
      GSK1265744 was tested in combination with representative anti-HIV agents, and no
      antagonistic effects were seen. These findings demonstrate that, similar to
      dolutegravir, GSK1265744 is differentiated as a new INSTI, having a markedly
      distinct resistance profile compared with earlier INSTIs, RAL, and elvitegravir
      (EVG). The collective data set supports further clinical development of
      GSK1265744. 

PMID- 25367909
TI  - Genomic epidemiology of Klebsiella pneumoniae in Italy and novel insights into
      the origin and global evolution of its resistance to carbapenem antibiotics.
AB  - Klebsiella pneumoniae is at the forefront of antimicrobial resistance for Gram
      negative pathogenic bacteria, as strains resistant to third-generation
      cephalosporins and carbapenems are widely reported. The worldwide diffusion of
      these strains is of great concern due to the high morbidity and mortality often
      associated with K. pneumoniae infections in nosocomial environments. We sequenced
      the genomes of 89 K. pneumoniae strains isolated in six Italian hospitals.
      Strains were selected based on antibiotypes, regardless of multilocus sequence
      type, to obtain a picture of the epidemiology of K. pneumoniae in Italy. Thirty
      one strains were carbapenem-resistant K. pneumoniae carbapenemase producers, 29
      were resistant to third-generation cephalosporins, and 29 were susceptible to the
      aforementioned antibiotics. The genomes were compared to all of the sequences
      available in the databases, obtaining a data set of 319 genomes spanning the
      known diversity of K. pneumoniae worldwide. Bioinformatic analyses of this global
      data set allowed us to construct a whole-species phylogeny, to detect patterns of
      antibiotic resistance distribution, and to date the differentiation between
      specific clades of interest. Finally, we detected an ~ 1.3-Mb recombination that
      characterizes all of the isolates of clonal complex 258, the most widespread
      carbapenem-resistant group of K. pneumoniae. The evolution of this complex was
      modeled, dating the newly detected and the previously reported recombination
      events. The present study contributes to the understanding of K. pneumoniae
      evolution, providing novel insights into its global genomic characteristics and
      drawing a dated epidemiological scenario for this pathogen in Italy.

PMID- 25367910
TI  - Optimization of a nucleic acid-based reporter system to detect Mycobacterium
      tuberculosis antibiotic sensitivity.
AB  - We previously reported the development of a prototype antibiotic sensitivity
      assay to detect drug-resistant Mycobacterium tuberculosis using infection by
      mycobacteriophage to create a novel nucleic acid transcript, a surrogate marker
      of mycobacterial viability, detected by reverse transcriptase PCR (M. C. Mulvey
      et al., mBio 3: e00312-11, 2012). This assay detects antibiotic resistance to all
      drugs, even drugs for which the resistance mechanism is unknown or complex: it is
      a phenotypic readout using nucleic acid detection. In this report, we describe
      development and characteristics of an optimized reporter system that directed
      expression of the RNA cyclase ribozyme, which generated circular RNA through an
      intramolecular splicing reaction and led to accumulation of a new nucleic acid
      sequence in phage-infected bacteria. These modifications simplified the assay,
      increased the limit of detection from 10(4) to <10(2) M. tuberculosis cells, and
      correctly identified the susceptibility profile of M. tuberculosis strains
      exposed for 16 h to either first-line or second-line antitubercular drugs. In
      addition to phenotypic drug resistance or susceptibility, the assay reported
      streptomycin MICs and clearly detected 10% drug-resistant cells in an otherwise
      drug-susceptible population. 

PMID- 25367911
TI  - Evaluation of pyrosequencing for detecting extensively drug-resistant
      Mycobacterium tuberculosis among clinical isolates from four high-burden
      countries.
AB  - Reliable molecular diagnostics, which detect specific mutations associated with
      drug resistance, are promising technologies for the rapid identification and
      monitoring of drug resistance in Mycobacterium tuberculosis isolates.
      Pyrosequencing (PSQ) has the ability to detect mutations associated with first-
      and second-line anti-tuberculosis (TB) drugs, with the additional advantage of
      being rapidly adaptable for the identification of new mutations. The aim of this
      project was to evaluate the performance of PSQ in predicting phenotypic drug
      resistance in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB)
      clinical isolates from India, South Africa, Moldova, and the Philippines. A total
      of 187 archived isolates were run through a PSQ assay in order to identify M.
      tuberculosis (via the IS6110 marker), and to detect mutations associated with
      M/XDR-TB within small stretches of nucleotides in selected loci. The molecular
      targets included katG, the inhA promoter and the ahpC-oxyR intergenic region for
      isoniazid (INH) resistance; the rpoB core region for rifampin (RIF) resistance;
      gyrA for fluoroquinolone (FQ) resistance; and rrs for amikacin (AMK), capreomycin
      (CAP), and kanamycin (KAN) resistance. PSQ data were compared to phenotypic
      mycobacterial growth indicator tube (MGIT) 960 drug susceptibility testing
      results for performance analysis. The PSQ assay illustrated good sensitivity for
      the detection of resistance to INH (94%), RIF (96%), FQ (93%), AMK (84%), CAP
      (88%), and KAN (68%). The specificities of the assay were 96% for INH, 100% for
      RIF, FQ, AMK, and KAN, and 97% for CAP. PSQ is a highly efficient diagnostic tool
      that reveals specific nucleotide changes associated with resistance to the first-
      and second-line anti-TB drug medications. This methodology has the potential to
      be linked to mutation-specific clinical interpretation algorithms for rapid
      treatment decisions. 

PMID- 25367912
TI  - Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for
      treatment of uncomplicated malaria in children in Zaire and Uige Provinces,
      angola.
AB  - The development of resistance to antimalarials is a major challenge for global
      malaria control. Artemisinin-based combination therapies, the newest class of
      antimalarials, are used worldwide but there have been reports of artemisinin
      resistance in Southeast Asia. In February through May 2013, we conducted open
      label, nonrandomized therapeutic efficacy studies of artemether-lumefantrine (AL)
      and dihydroartemisinin-piperaquine (DP) in Zaire and Uige Provinces in northern
      Angola. The parasitological and clinical responses to treatment in children with
      uncomplicated Plasmodium falciparum monoinfection were measured over 28 days, and
      the main outcome was a PCR-corrected adequate clinical and parasitological
      response (ACPR) proportion on day 28. Parasites from treatment failures were
      analyzed for the presence of putative molecular markers of resistance to
      lumefantrine and artemisinins, including the recently identified mutations in the
      K13 propeller gene. In the 320 children finishing the study, 25 treatment
      failures were observed: 24 in the AL arms and 1 in the DP arm. The PCR-corrected
      ACPR proportions on day 28 for AL were 88% (95% confidence interval [CI], 78 to
      95%) in Zaire and 97% (91 to 100%) in Uige. For DP, the proportions were 100% (95
      to 100%) in Zaire, and 100% (96 to 100%) in Uige. None of the treatment failures
      had molecular evidence of artemisinin resistance. In contrast, 91% of AL late
      treatment failures had markers associated with lumefantrine resistance on the day
      of failure. The absence of molecular markers for artemisinin resistance and the
      observed efficacies of both drug combinations suggest no evidence of artemisinin
      resistance in northern Angola. There is evidence of increased lumefantrine
      resistance in Zaire, which should continue to be monitored. 

PMID- 25367915
TI  - Overproduction of the MtrCDE efflux pump in Neisseria gonorrhoeae produces
      unexpected changes in cellular transcription patterns.
AB  - The global consequence of drug efflux gene overexpression in bacteria has not
      been specifically analyzed because strains showing high-level expression
      typically have mutations in genes encoding regulatory proteins that control other
      genes. Results from a transcriptional profiling study performed with a strain of
      Neisseria gonorrhoeae that is capable of high-level transcription of the mtrCDE
      efflux pump operon independently of control by cognate regulatory proteins
      revealed that its overexpression has ramifications for systems other than drug
      efflux. 

PMID- 25367913
TI  - Systematic review of biomarkers to monitor therapeutic response in leishmaniasis.
AB  - Recently, there has been a renewed interest in the development of new drugs for
      the treatment of leishmaniasis. This has spurred the need for pharmacodynamic
      markers to monitor and compare therapies specifically for visceral leishmaniasis,
      in which the primary recrudescence of parasites is a particularly long-term event
      that remains difficult to predict. We performed a systematic review of studies
      evaluating biomarkers in human patients with visceral, cutaneous, and post-kala
      azar dermal leishmaniasis, which yielded a total of 170 studies in which 53
      potential pharmacodynamic biomarkers were identified. In conclusion, the large
      majority of these biomarkers constituted universal indirect markers of activation
      and subsequent waning of cellular immunity and therefore lacked specificity.
      Macrophage-related markers demonstrate favorable sensitivity and times to
      normalcy, but more evidence is required to establish a link between these markers
      and clinical outcome. Most promising are the markers directly related to the
      parasite burden, but future effort should be focused on optimization of molecular
      or antigenic targets to increase the sensitivity of these markers. In general,
      future research should focus on the longitudinal evaluation of the
      pharmacodynamic biomarkers during treatment, with an emphasis on the correlation
      of studied biomarkers and clinical parameters. 

PMID- 25367914
TI  - The resistome of Pseudomonas aeruginosa in relationship to phenotypic
      susceptibility.
AB  - Many clinical isolates of Pseudomonas aeruginosa cause infections that are
      difficult to eradicate due to their resistance to a wide variety of antibiotics.
      Key genetic determinants of resistance were identified through genome sequences
      of 390 clinical isolates of P. aeruginosa, obtained from diverse geographic
      locations collected between 2003 and 2012 and were related to microbiological
      susceptibility data for meropenem, levofloxacin, and amikacin. beta-Lactamases
      and integron cassette arrangements were enriched in the established multidrug
      resistant lineages of sequence types ST111 (predominantly O12) and ST235 (O11).
      This study demonstrates the utility of next-generation sequencing (NGS) in
      defining relevant resistance elements and highlights the diversity of resistance
      determinants within P. aeruginosa. This information is valuable in furthering the
      design of diagnostics and therapeutics for the treatment of P. aeruginosa
      infections. 

PMID- 25367917
TI  - Chromosome-mediated multidrug resistance in Salmonella enterica serovar Typhi.
AB  - A salmonella genomic island, designated SGI11, was found in 18 of 26 multidrug
      resistant Salmonella enterica serovar Typhi isolates from Bangladesh. SGI11 was
      an IS1 composite transposon and carried 7 resistance genes that conferred
      resistance to 5 first-line antimicrobials. Eleven of the 18 SGI11-carrying S.
      Typhi isolates had developed resistance to high levels of ciprofloxacin.

PMID- 25367916
TI  - Artemisinins, new miconazole potentiators resulting in increased activity against
      Candida albicans biofilms.
AB  - Mucosal biofilm-related fungal infections are very common, and the incidence of
      recurrent oral and vulvovaginal candidiasis is significant. As resistance to
      azoles (the preferred treatment) is occurring, we aimed at identifying compounds
      that increase the activity of miconazole against Candida albicans biofilms. We
      screened 1,600 compounds of a drug-repositioning library in combination with a
      subinhibitory concentration of miconazole. Synergy between the best identified
      potentiators and miconazole was characterized by checkerboard analyses and
      fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate,
      and artesunate act synergistically with miconazole in affecting C. albicans
      biofilms. Synergy was most pronounced for artesunate and structural homologues
      thereof. No synergistic effect could be observed between artesunate and
      fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the
      antibiofilm activity of miconazole by artesunate, pointing to potential
      combination therapy consisting of miconazole and artesunate to treat C. albicans
      biofilm-related infections. 

PMID- 25367918
TI  - Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia,
      and Insomnia in Older Children and Adolescents With Down Syndrome.
AB  - Over a 10-year period in a Down syndrome Clinic, 11 children and adolescents were
      encountered with a history of new-onset (8) or worsening (3) autistic
      characteristics. Ten of the 11 (91%) had cognitive decline to a dementia-like
      state and 9 of the 11 (82%) new-onset insomnia. The mean age at which symptoms
      developed was 11.4 years (standard deviation = 3.6 years; range 5-14 years), an
      older age than usual for autistic regression in Down syndrome. Ten of 11 cases
      (91%) had elevated ("positive") thyroperoxidase antibody titers compared to only
      5 of 21 (23%) age-matched control subjects with Down syndrome (P < .001). At
      follow-up at a mean age of 20.7 years (standard deviation = 3.9 years), 8 of the
      11 (73%) were at least somewhat better. Down syndrome disintegrative disorder
      seems an appropriate name for this newly recognized clinical association, which
      may be due to autoimmunity. 

PMID- 25367920
TI  - Incorrect conclusions about unpublished pharmaceutical research.

PMID- 25367921
TI  - Induction of labour.

PMID- 25367922
TI  - Induction of labour.

PMID- 25367923
TI  - The authors respond.

PMID- 25367924
TI  - Thank you for saying this.

PMID- 25367925
TI  - Otitis media and Bell palsy.

PMID- 25367928
TI  - Guiding genomics use in cancer care.

PMID- 25367929
TI  - CTC clusters more likely to cause metastasis.

PMID- 25367930
TI  - KNSTRN deemed an oncogene.

PMID- 25367931
TI  - Prostate cancer organoids make debut.

PMID- 25367932
TI  - CRISPR used to create mouse models.

PMID- 25367933
TI  - PD-1 inhibitor approved for melanoma.

PMID- 25367935
TI  - FDA announces plans to regulate LDTs.

PMID- 25367936
TI  - IGF1R signaling is a therapeutic target in ALK fusion-positive lung cancer.

PMID- 25367937
TI  - Small molecules inhibit the RAS-like small GTPases RALA and RALB.
AB  - Small molecules that selectively bind RAL-GDP inhibit RAL activity and suppress
      tumor growth. 

PMID- 25367938
TI  - Diet-induced dysbiosis influences susceptibility to intestinal cancer.
AB  - A high-fat diet alters the composition of the gut microbiome to promote
      intestinal tumorigenesis. 

PMID- 25367939
TI  - The NOTCH pathway plays a tumor suppressive role in bladder cancer.
AB  - Inactivation of the NOTCH pathway drives bladder tumorigenesis. 

PMID- 25367940
TI  - RBM4-regulated alternative splicing suppresses tumorigenesis.
AB  - RBM4 inhibits cancer cell growth and migration by regulating cancer-associated
      gene splicing. 

PMID- 25367941
TI  - The focally amplified lncRNA FAL1 exhibits oncogenic activity.
AB  - FAL1 is an oncogenic lncRNA that promotes cancer cell growth in part via
      repression of p21. 

PMID- 25367942
TI  - The immunosuppressive activity of MDSCs requires expression of CHOP.
AB  - The stress sensor CHOP enhances the accumulation and inhibitory activity of MDSCs
      in tumors. 

PMID- 25367943
TI  - Cone precursor cells are the cell-of-origin in retinoblastoma.
AB  - RB loss in human cone precursor cells promotes proliferation and retinoblastoma
      formation. 

PMID- 25367944
TI  - IRBIT promotes allosteric inhibition of ribonucleotide reductase.
AB  - IRBIT inhibits ribonucleotide reductase (RNR) by stabilizing dATP binding to the
      RNR activity site. 

PMID- 25367945
TI  - PRKD1 mutations characterize salivary gland polymorphous low-grade
      adenocarcinoma.
AB  - Salivary gland polymorphous low-grade adenocarcinomas commonly harbor activating
      PRKD1 mutations. 

PMID- 25367946
TI  - Collateral genome instability by DNA damage in mitosis.
AB  - SUMMARY: Chromosome segregation errors and DNA damage are in a vicious cycle in
      cancer cells. Bakhoum and colleagues show that the molecular response to damaged
      DNA during mitosis impairs the chromosome segregation machinery, adding a new
      level to the already dangerous relations between different kinds of genomic
      instability.

PMID- 25367947
TI  - Escaping out of the brain.
AB  - SUMMARY: Technological development in the field of circulating biomarkers has
      allowed the identification of circulating tumor cells in the peripheral blood of
      patients with glioblastoma. This opens a new avenue of research with implications
      for the understanding and clinical managing of this fatal disease.

PMID- 25367948
TI  - Insights into the mechanism of organ-specific cancer metastasis.
AB  - SUMMARY: Lucas and colleagues nominate transmembrane serine protease type II
      (TMPRSS2) as an important player in the initiation of epithelial-mesenchymal
      transition (EMT) in prostate cancer. Cancer cells maintain androgen receptor
      regulated cytoplasmic TMPRSS2 expression, which facilitates EMT invasion and
      metastasis in model systems through hepatocyte growth factor and c-MET signaling.
      In addition to providing a rationale for potentially targeting this organ
      specific enabler of metastatic disease progression, this study also highlights
      the importance of understanding how organ/tissue-specific genes are co-opted in
      the context of cancer.

PMID- 25367949
TI  - Social interactomes for enabling research communities.
AB  - SUMMARY: Data-driven analyses of scientific abstracts with web apps such as
      "abstract interactomes" provide a new visualization tool for the biomedical
      research community to interactively navigate a rich assembly of investigators and
      identify common research topics. Alternative conference formats such as "social
      interactomes," with structured, albeit informal, discussions among attendees, are
      able to engage fellows and top investigators, facilitate the exchange of ideas,
      and encourage data sharing and future collaborations.

PMID- 25367950
TI  - AR-V7 predicts prostate cancer treatment response.

PMID- 25367951
TI  - Ufmylation of ASC1 is essential for breast cancer development.
AB  - UFM1 modifies ASC1 to promote ERalpha transactivation and development of breast
      cancer. 

PMID- 25367952
TI  - MAFG mediates CIMP in BRAF-mutant colorectal cancer.
AB  - An MAFG-containing corepressor complex induces CIMP in BRAF(V600E)-positive
      colorectal cancer. 

PMID- 25367953
TI  - Chromosomal translocations are mediated by canonical NHEJ in human cells.
AB  - In contrast to mice, human cells require canonical NHEJ for DSB-induced
      chromosomal translocations. 

PMID- 25367954
TI  - BCR-ABL1 compound mutations drive ponatinib resistance.
AB  - BCR-ABL1 compound mutations harboring T315I are resistant to multiple TKIs,
      including ponatinib. 

PMID- 25367955
TI  - Loss of PRC2 function promotes MPNST pathogenesis.
AB  - Genetic inactivation of PRC2 components, NF1, and CDKN2A are frequently detected
      in MPNSTs. 

PMID- 25367956
TI  - Vagal innervation is necessary for gastric tumorigenesis.
AB  - The vagus nerve regulates gastric stem cell expansion and promotes gastric
      tumorigenesis. 

PMID- 25367957
TI  - Genomic profiling provides insight into chromophobe renal cell carcinoma.
AB  - Features of the genomic landscape of ChRCC distinguish it from other RCC
      subtypes. 

PMID- 25367958
TI  - T-ALL pathogenesis requires a NOTCH1-driven MYC enhancer.
AB  - A NOTCH1-bound MYC enhancer is necessary for normal T-cell development and NOTCH1
      induced T-ALL. 

PMID- 25367959
TI  - Erlotinib plus bevacizumab is effective in EGFR-mutant NSCLC.
AB  - The combination of erlotinib and bevacizumab prolongs PFS in patients with EGFR
      mutant NSCLC. 

PMID- 25367960
TI  - Asparagine protects tumor cells from glutamine depletion-induced cell death.
AB  - Asparagine promotes the survival of cancer cells in response to glutamine
      withdrawal. 

PMID- 25367961
TI  - GNAS a tumor suppressor in medulloblastoma.

PMID- 25367962
TI  - Metabolic rewiring is required for epithelial-mesenchymal transition.
AB  - Expression of metabolic genes such as dihydropyrimidine dehydrogenase (DPYD) is
      essential for EMT. 

PMID- 25367963
TI  - Tumor hypoxia is a therapeutic target in soft-tissue sarcoma.
AB  - TH-302 shows antitumor activity in combination with doxorubicin in advanced soft
      tissue sarcoma. 

PMID- 25367964
TI  - BRAF has a kinase-independent role in MAPK signaling.
AB  - BRAF has a regulatory role in the MAPK pathway that is dependent on its
      interaction with MEK1. 

PMID- 25367965
TI  - Dovitinib reduces prostate cancer bone metastases.

PMID- 25367966
TI  - Putting molecular profiling to the test.

PMID- 25367967
TI  - FDA aims to boost diversity in trials.

PMID- 25367968
TI  - Bacteria attack tumors from the inside out.

PMID- 25367969
TI  - Probing poorly understood genes.

PMID- 25367970
TI  - Novel molecule hits key cancer target.

PMID- 25367971
TI  - NCI launches ALCHEMIST.

PMID- 25367972
TI  - Transcriptional silencing by polycomb-group proteins.
AB  - Polycomb-group (PcG) genes encode chromatin proteins involved in stable and
      heritable transcriptional silencing. PcG proteins participate in distinct
      multimeric complexes that deposit, or bind to, specific histone modifications
      (e.g., H3K27me3 and H2AK119ub1) to prevent gene activation and maintain repressed
      chromatin domains. PcG proteins are evolutionary conserved and play a role in
      processes ranging from vernalization and seed development in plants, over X
      chromosome inactivation in mammals, to the maintenance of stem cell identity. PcG
      silencing is medically relevant as it is often observed in human disorders,
      including cancer, and tissue regeneration, which involve the reprogramming of PcG
      controlled target genes. 

PMID- 25367974
TI  - Host cell invasion by medically important fungi.
AB  - To infect the host and cause disease, many medically important fungi invade
      normally nonphagocytic host cells, such as endothelial cells and epithelial
      cells. Host cell invasion is a two-step process consisting of adherence followed
      by invasion. There are two general mechanisms of host cell invasion, induced
      endocytosis and active penetration. Furthermore, fungi can traverse epithelial or
      endothelial cell barriers either by proteolytic degradation of intercellular
      tight junctions or via a Trojan horse mechanism in which they are transported by
      leukocytes. Although these mechanisms of host cell invasion have been best
      studied using Candida albicans and Cryptococcus neoformans, it is probable that
      other invasive fungi also use one or more of these mechanisms to invade host
      cells. Identification of these invasion mechanisms holds promise to facilitate
      the development of new approaches to inhibit fungal invasion and thereby prevent
      disease. 

PMID- 25367973
TI  - Pneumocystis.
AB  - Since its initial misidentification as a trypanosome some 100 years ago,
      Pneumocystis has remained recalcitrant to study. Although we have learned much,
      we still do not have definitive answers to such basic questions as, where is the
      reservoir of infection, how does Pneumocystis reproduce, what is the mechanism of
      infection, and are there true species of Pneumocystis? The goal of this review is
      to provide the reader the most up to date information available about the biology
      of Pneumocystis and the disease it produces. 

PMID- 25367978
TI  - Prostate cancer immunotherapy: beyond immunity to curability.
AB  - Metastatic prostate cancer is the second leading cause of death from cancer in
      the United States. It is the first prevalent cancer in which overall survival in
      advanced disease is modestly, but objectively, improved with outpatient delivered
      dendritic cell-based immunotherapy. More prostate cancer patients have enrolled
      through Facebook and trusted-site Internet searches in clinical trials for
      prostate cancer vaccine-based immunotherapy than in immunotherapy trials for
      lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7
      years. Exceptional responses to anti-CTLA-4 treatment have been documented in
      clinics, and prostate cancer neoantigen characterization and T-cell clonotyping
      are in their research ascendancy. The prostate is an accessory organ; it is not
      required for fertility, erectile function, or urinary continence. The true
      evolutionary advantage of having a prostate for male mammalian physiology is a
      topic of speculation in seminar rooms and on bar stools, but it remains unknown.
      Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000
      normal human prostate lineage-unique open reading frames that can be targeted for
      immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific
      autoimmunity. This bioengineered graft-versus-prostate disease is a powerful
      strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to
      prostate cancer can be overcome at every clinical stage of presentation. This
      Cancer Immunology at the Crossroads article aims to present advances in the past
      two decades of basic, translational, and clinical research in prostate cancer,
      including bioengineering B-cell and T-cell responses, and ongoing prostate cancer
      immunotherapy trials.

PMID- 25367975
TI  - The spectrum of fungi that infects humans.
AB  - Few among the millions of fungal species fulfill four basic conditions necessary
      to infect humans: high temperature tolerance, ability to invade the human host,
      lysis and absorption of human tissue, and resistance to the human immune system.
      In previously healthy individuals, invasive fungal disease is rare because
      animals' sophisticated immune systems evolved in constant response to fungal
      challenges. In contrast, fungal diseases occur frequently in immunocompromised
      patients. Paradoxically, successes of modern medicine have put increasing numbers
      of patients at risk for invasive fungal infections. Uncontrolled HIV infection
      additionally makes millions vulnerable to lethal fungal diseases. A concerted
      scientific and social effort is needed to meet these challenges. 

PMID- 25367980
TI  - It takes a community.

PMID- 25367977
TI  - The immunological synapse.
AB  - The molecular interactions underlying regulation of the immune response take
      place in a nanoscale gap between T cells and antigen-presenting cells, termed the
      immunological synapse. If these interactions are regulated appropriately, the
      host is defended against a wide range of pathogens and deranged host cells. If
      these interactions are disregulated, the host is susceptible to pathogens or
      tumor escape at one extreme and autoimmunity at the other. Strategies targeting
      the synapse have helped to establish immunotherapy as a mainstream element in
      cancer treatment. This Masters' primer will cover the basics of the immunological
      synapse and some of the applications to tumor immunology.

PMID- 25367979
TI  - Prevention of skin carcinogenesis by the beta-blocker carvedilol.
AB  - The stress-related catecholamine hormones and the alpha- and beta-adrenergic
      receptors (alpha- and beta-AR) may affect carcinogenesis. The beta-AR GRK/beta
      arrestin biased agonist carvedilol can induce beta-AR-mediated transactivation of
      the EGFR. The initial purpose of this study was to determine whether carvedilol,
      through activation of EGFR, can promote cancer. Carvedilol failed to promote
      anchorage-independent growth of JB6 P(+) cells, a skin cell model used to study
      tumor promotion. However, at nontoxic concentrations, carvedilol dose dependently
      inhibited EGF-induced malignant transformation of JB6 P(+) cells, suggesting that
      carvedilol has chemopreventive activity against skin cancer. Such effect was not
      observed for the beta-AR agonist isoproterenol and the beta-AR antagonist
      atenolol. Gene expression, receptor binding, and functional studies indicate that
      JB6 P(+) cells only express beta2-ARs. Carvedilol, but not atenolol, inhibited
      EGF-mediated activator protein-1 (AP-1) activation. A topical 7,12
      dimethylbenz(alpha)anthracene (DMBA)-induced skin hyperplasia model in SENCAR
      mice was utilized to determine the in vivo cancer preventative activity of
      carvedilol. Both topical and oral carvedilol treatment inhibited DMBA-induced
      epidermal hyperplasia (P < 0.05) and reduced H-ras mutations; topical treatment
      being the most potent. However, in models of established cancer, carvedilol had
      modest to no inhibitory effect on tumor growth of human lung cancer A549 cells in
      vitro and in vivo. In conclusion, these results suggest that the cardiovascular
      drug carvedilol may be repurposed for skin cancer chemoprevention, but may not be
      an effective treatment of established tumors. More broadly, this study suggests
      that beta-ARs may serve as a novel target for cancer prevention.

PMID- 25367976
TI  - Fungal morphogenesis.
AB  - Morphogenesis in fungi is often induced by extracellular factors and executed by
      fungal genetic factors. Cell surface changes and alterations of the
      microenvironment often accompany morphogenetic changes in fungi. In this review,
      we will first discuss the general traits of yeast and hyphal morphotypes and how
      morphogenesis affects development and adaptation by fungi to their native niches,
      including host niches. Then we will focus on the molecular machinery responsible
      for the two most fundamental growth forms, yeast and hyphae. Last, we will
      describe how fungi incorporate exogenous environmental and host signals together
      with genetic factors to determine their morphotype and how morphogenesis, in
      turn, shapes the fungal microenvironment. 

PMID- 25367981
TI  - Building healthy communities beyond the hospital walls.

PMID- 25367982
TI  - Integrating public health and community development to tackle neighborhood
      distress and promote well-being.
AB  - Recently there have been calls for public health to reconnect to urban planning
      in ways that emphasize the impact of place on health and that address fundamental
      causes of poor health, such as poverty, social inequality, and discrimination.
      Community developers have realized that poor health limits individuals' and
      communities' economic potential and have begun to integrate into their work such
      neighborhood health issues as access to fresh food and open space. In this
      article we review recent shifts in the community development field and give
      examples of programs that operate at the intersection of community development,
      public health, and civic engagement. For example, in Sacramento, California, the
      Building Healthy Communities program successfully promoted the creation of
      community gardens and bike paths and the redevelopment of brownfields. A major
      housing revitalization initiative in San Francisco, California, known as
      Sunnydale-Velasco, is transforming the city's largest public housing site into a
      mixed-income community that provides existing residents with new housing,
      infrastructure, services, and amenities. These examples and others illustrate the
      need to identify and make use of interdisciplinary approaches to ensure that all
      places are strong platforms for economic mobility, full democratic participation,
      and community health. 

PMID- 25367983
TI  - Using pay-for-success to increase investment in the nonmedical determinants of
      health.
AB  - The combination of fee-for-service payments and the US health care system's
      standing commitment to treating existing illness discourages spending on the
      behavioral, social, and environmental (that is, the nonmedical) conditions that
      contribute most to long-term health. Pay-for-success, alternatively known as
      social impact bonds, or SIBs, offers a possible solution. The pay-for-success
      model relies on an investor that is willing to fund a nonmedical intervention up
      front while bearing the risk that the intervention may fail to prevent disease in
      the future. Should the intervention succeed, however, the investor is repaid in
      full by a predetermined payer (such as a public health agency) and receives an
      additional return on its investment as a reward for taking on the risk. Pay-for
      success pilots are being developed to reduce asthma-related emergencies among
      children, poor birth outcomes, and the progression of prediabetes to diabetes,
      among other applications. These efforts, supported by key policy reforms such as
      public agency data sharing and coordinated care, promise to increase the number
      of evidence-based nonmedical service providers and seed a new market that values
      health, not just health care. 

PMID- 25367984
TI  - A health-in-all-policies approach addresses many of Richmond, California's place
      based hazards, stressors.
AB  - Poor and minority residents of Richmond, California, have faced a host of place
      based hazards and stressors such as pollution, gun violence, and a dearth of
      economic opportunities, all of which have likely contributed to their poor health
      outcomes. In this article we describe the city's efforts to reverse its fortunes
      by embracing a health-in-all-policies strategy for community development.
      Starting in 2007, the city organized a series of participatory planning projects
      with residents, community activists, school officials, and other stakeholders to
      ensure that the city took health equity into account when devising each phase of
      its new community development strategy. The result was an approach designed to
      address the social determinants of health by directing development resources
      toward vulnerable communities and by adopting a health-in-all-policies ordinance.
      Specific projects focused on improving the built environment and community safety
      and redirecting government funds to areas of social need. The process has
      contributed to rising levels of resident satisfaction about personal health, the
      direction the city is taking, and the quality of neighborhood development.
      Richmond's experience suggests that adopting a health-in-all-policies strategy is
      one way to promote health equity in distressed cities. 

PMID- 25367985
TI  - Case study: San Francisco's use of neighborhood indicators to encourage healthy
      urban development.
AB  - Neighborhood indicators are quantitative measures of neighborhood quality,
      including measures of attributes such as crime, noise, proximity to parks,
      transit services, social capital, and student performance. In 2007 the San
      Francisco Department of Public Health, with broad public input, developed a
      comprehensive system of neighborhood indicators to inform, influence, and monitor
      decisions made by the Department of City Planning and other community development
      institutions. Local public agencies, businesses, and citizens' groups used the
      indicators to identify disparities in environmental and social conditions, inform
      and shape neighborhood land use plans, select appropriate sites for development
      projects, craft new environmental regulations, and justify demands on developers
      to make financial contributions to community infrastructure. Among other things,
      the use of indicators contributed to policies to prevent residential
      displacement, a city ordinance requiring stricter building ventilation standards
      in areas with high air pollution, and the redeployment of traffic police to high
      injury corridors. Data that can be used to create neighborhood indicators are
      increasingly available, and participation by public health and health care
      institutions in the indicators' development, dissemination, and application could
      help improve several conditions that contribute to poor population health. 

PMID- 25367986
TI  - Building healthy communities: establishing health and wellness metrics for use
      within the real estate industry.
AB  - It is increasingly well recognized that the design and operation of the
      communities in which people live, work, learn, and play significantly influence
      their health. However, within the real estate industry, the health impacts of
      transportation, community development, and other construction projects, both
      positive and negative, continue to operate largely as economic externalities:
      unmeasured, unregulated, and for the most part unconsidered. This lack of
      transparency limits communities' ability to efficiently advocate for real estate
      investment that best promotes their health and well-being. It also limits market
      incentives for innovation within the real estate industry by making it more
      difficult for developers that successfully target health behaviors and outcomes
      in their projects to differentiate themselves competitively. In this article we
      outline the need for actionable, community-relevant, practical, and valuable
      metrics jointly developed by the health care and real estate sectors to better
      evaluate and optimize the "performance" of real estate development projects from
      a population health perspective. Potential templates for implementation,
      including the successful introduction of sustainability metrics by the green
      building movement, and preliminary data from selected case-study projects are
      also discussed. 

PMID- 25367987
TI  - A framework to extend community development measurement to health and well-being.
AB  - Measurement can help community development and health practitioners align and
      optimize their investments and leverage additional resources to achieve shared
      goals. However, there is no clear guidance for reconciling the established
      systems for measuring community development activities and outputs-such as
      housing units built, jobs created, and people served-with the outcomes and
      impacts of health. We therefore reviewed community development measurement
      systems-encompassing assessment, monitoring, evaluation, and standards-and
      identified strategies for using those systems to support health in community
      development decision making. We highlight promising innovations by organizations
      such as the Reinvestment Fund and NeighborWorks America and place these in an
      ecosystem framework to illustrate opportunities for shared measurement. We then
      discuss policies and processes to build the ecosystem's infrastructure, balance
      stakeholders' priorities within the ecosystem, and use it to drive investments in
      health. 

PMID- 25367988
TI  - A simplified framework for incorporating health into community development
      initiatives.
AB  - Community development seeks to address the consequences of poverty through
      initiatives that improve housing, economic opportunity, service availability, and
      community capacity. There is growing recognition that the fields of community
      development and public health have much in common with regard to target
      populations, objectives, and challenges. Individual and neighborhood-level
      poverty are well-documented risk factors for illness and premature death. But
      relatively few developers systematically analyze how their projects could affect
      the health of the target community. Tools and metrics that facilitate
      incorporating health into planning, financing, and implementing new community
      development projects and programs will foster more widespread and productive
      collaboration between these two fields. We propose a simple framework to
      facilitate the identification and measurement of potential health effects,
      actions to optimize anticipated positive impacts, and strategies to mitigate
      potential negative impacts. The framework is drawn from an analysis of health
      impact assessments and includes four elements: identifying the health status of
      the population served, considering neighborhood-level influences on health,
      building design features important to health, and incorporating community
      engagement and capacity-building activities into the initiative. 

PMID- 25367989
TI  - The child opportunity index: improving collaboration between community
      development and public health.
AB  - Improving neighborhood environments for children through community development
      and other interventions may help improve children's health and reduce inequities
      in health. A first step is to develop a population-level surveillance system of
      children's neighborhood environments. This article presents the newly developed
      Child Opportunity Index for the 100 largest US metropolitan areas. The index
      examines the extent of racial/ethnic inequity in the distribution of children
      across levels of neighborhood opportunity. We found that high concentrations of
      black and Hispanic children in the lowest-opportunity neighborhoods are pervasive
      across US metropolitan areas. We also found that 40 percent of black and 32
      percent of Hispanic children live in very low-opportunity neighborhoods within
      their metropolitan area, compared to 9 percent of white children. This inequity
      is greater in some metropolitan areas, especially those with high levels of
      residential segregation. The Child Opportunity Index provides perspectives on
      child opportunity at the neighborhood and regional levels and can inform place
      based community development interventions and non-place-based interventions that
      address inequities across a region. The index can also be used to meet new
      community data reporting requirements under the Affordable Care Act. 

PMID- 25367991
TI  - Healthy Futures Fund links housing, health.
AB  - The ambitious $100 million collaboration among the Kresge Foundation, the Local
      Initiatives Support Corporation, and Morgan Stanley aims to make health an
      essential part of community development. 

PMID- 25367990
TI  - 'Pharmacy deserts' are prevalent in Chicago's predominantly minority communities,
      raising medication access concerns.
AB  - Attempts to explain and address disparities in the use of prescription
      medications have focused almost exclusively on their affordability. However, the
      segregation of residential neighborhoods by race or ethnicity also may influence
      access to the pharmacies that, in turn, provide access to prescription
      medications within a community. We examined whether trends in the availability of
      pharmacies varied across communities in Chicago with different racial or ethnic
      compositions. We also examined the geographic accessibility of pharmacies to
      determine whether "pharmacy deserts," or low-access neighborhoods, were more
      common in segregated black and Hispanic communities than elsewhere. We found that
      throughout the period 2000-2012 the number of pharmacies was lower in segregated
      minority communities than in segregated white communities and integrated
      communities. In 2012 there were disproportionately more pharmacy deserts in
      segregated black communities, as well as in low-income communities and federally
      designated Medically Underserved Areas. Our findings suggest that public policies
      aimed at improving access to prescription medications may need to address factors
      beyond insurance coverage and medication affordability. Such policies could
      include financial incentives to locate pharmacies in pharmacy deserts or the
      incorporation of pharmacies into community health centers in Medically
      Underserved Areas. 

PMID- 25367992
TI  - Cross-sector collaboration to improve community health: a view of the current
      landscape.
AB  - Collaboration between the health and community development sectors has gained
      increased attention as a means of accelerating progress to improve community
      health. This article offers an empirical perspective on the general status of
      such collaboration based on results from a national survey of practitioners in
      the community development and health fields. Study results show that cross-sector
      efforts to improve health are widespread across the United States. Community
      development organizations, including community development financial
      institutions, support a wide spectrum of activities addressing both social
      determinants of health and the immediate needs of communities. However, the means
      of assessing the impacts of these joint community health improvement initiatives
      appear limited. We highlight opportunities for building on present momentum and
      for measuring results in a way that expands the evidence base on effective
      collaborative efforts between the two sectors. 

PMID- 25367993
TI  - Hennepin Health: a safety-net accountable care organization for the expanded
      Medicaid population.
AB  - Health care payment and delivery models that challenge providers to be
      accountable for outcomes have fueled interest in community-level partnerships
      that address the behavioral, social, and economic determinants of health. We
      describe how Hennepin Health--a county-based safety-net accountable care
      organization in Minnesota--has forged such a partnership to redesign the health
      care workforce and improve the coordination of the physical, behavioral, social,
      and economic dimensions of care for an expanded community of Medicaid
      beneficiaries. Early outcomes suggest that the program has had an impact in
      shifting care from hospitals to outpatient settings. For example, emergency
      department visits decreased 9.1 percent between 2012 and 2013, while outpatient
      visits increased 3.3 percent. An increasing percentage of patients have received
      diabetes, vascular, and asthma care at optimal levels. At the same time, Hennepin
      Health has realized savings and reinvested them in future improvements. Hennepin
      Health offers lessons for counties, states, and public hospitals grappling with
      the problem of how to make the best use of public funds in serving expanded
      Medicaid populations and other communities with high needs.

PMID- 25367994
TI  - The NewYork-Presbyterian Regional Health Collaborative: a three-year progress
      report.
AB  - The Washington Heights-Inwood section of Manhattan is a predominantly poor
      Hispanic community with disproportionately high rates of chronic disease,
      including asthma, diabetes, and congestive heart failure. In October 2010,
      NewYork-Presbyterian Hospital, in association with the Columbia University
      Medical Center, launched an integrated network of patient-centered medical homes
      that were linked to other providers and community-based resources and formed a
      "medical village." Three years later, a study of 5,852 patients who had some
      combination of diabetes, asthma, and congestive heart failure found that
      emergency department visits and hospitalizations had been reduced by 29.7 percent
      and 28.5 percent, respectively, compared to the year before implementation of the
      network. Thirty-day readmissions and average length-of-stay declined by 36.7
      percent and 4.9 percent, respectively. Patient satisfaction scores improved
      across all measures. Financially, NewYork-Presbyterian experienced a short-term
      return on investment of 11 percent. Some of the gain was a result of increased
      reimbursements from New York State. Nonetheless, these findings demonstrate that
      academic medical centers can improve outcomes for poor communities by building
      regional care models centering on medical homes that incorporate patient-centered
      processes and are linked through information systems and service collaborations
      to hospitals, specialty practices, and community-based providers and
      organizations. 

PMID- 25367996
TI  - Applying a 3.0 transformation framework to guide large-scale health system
      reform.
AB  - Implementation of the Affordable Care Act is unleashing historic new efforts
      aimed at reforming the US health system. Many important incremental improvements
      are under way, yet there is a growing recognition that more transformative
      changes are necessary if the health care system is to do a better job of
      optimizing population health. While the concept of the Triple Aim-dedicated to
      improving the experience of care, the health of populations, and lowering per
      capita costs of care-has been used to help health care providers and health care
      systems focus their efforts on costs, quality, and outcomes, it does not provide
      a roadmap for a new system. In this article we describe the 3.0 Transformation
      Framework we developed to stimulate thinking and support the planning and
      development of the new roadmap for the next generation of the US health care
      system. With a focus on optimizing population health over the life span, the
      framework suggests how a system designed to better manage chronic disease care
      could evolve into a system designed to enhance population health. We describe how
      the 3.0 Transformation Framework has been used and applied in national, state,
      and local settings, and we suggest potential next steps for its wider application
      and use. 

PMID- 25367995
TI  - Housing code violation density associated with emergency department and hospital
      use by children with asthma.
AB  - Local agencies that enforce housing policies can partner with the health care
      system to target pediatric asthma care. These agencies retain data that can be
      used to pinpoint potential clusters of high asthma morbidity. We sought to assess
      whether the density of housing code violations in census tracts-the in-tract
      asthma-relevant violations (such as the presence of mold or cockroaches) divided
      by the number of housing units-was associated with population-level asthma
      morbidity and could be used to predict a hospitalized patient's risk of
      subsequent morbidity. We found that increased density in housing code violations
      was associated with population-level morbidity independent of poverty, and that
      the density explained 22 percent of the variation in rates of asthma-related
      emergency department visits and hospitalizations. Children who had been
      hospitalized for asthma had 1.84 greater odds of a revisit to the emergency
      department or a rehospitalization within twelve months if they lived in the
      highest quartile of housing code violation tracts, compared to those living in
      the lowest quartile. Integrating housing and health data could highlight at-risk
      areas and patients for targeted interventions. 

PMID- 25367997
TI  - The 340B discount program: outpatient prescription dispensing patterns through
      contract pharmacies in 2012.
AB  - Section 340B of the Public Health Service Act provides qualified organizations
      serving vulnerable populations with deep discounts for some outpatient
      medications. A 2010 regulatory change widely expanded the 340B program's reach,
      allowing these organizations to contract with retail pharmacies to dispense
      medications for eligible patients. Little is known about which medications are
      dispensed by contract pharmacies under the expanded program. We provide the first
      comparison of 340B prescriptions and all prescriptions dispensed in contract
      pharmacies. We used 2012 data from Walgreens, the national leader in 340B
      contract pharmacies. Medications used to treat chronic conditions such as
      diabetes, high cholesterol levels, asthma, and depression accounted for an
      overwhelming majority of all prescriptions dispensed at Walgreens as part of the
      340B program. A higher percentage of antiretrovirals used to treat HIV/AIDS were
      dispensed through 340B prescriptions than through all prescriptions dispensed at
      Walgreens. The majority of 340B prescriptions dispensed at Walgreens originated
      at tuberculosis clinics, consolidated health centers, disproportionate-share
      hospitals, and Ryan White clinics. Our results suggest that 340B contract
      pharmacies dispense medications used to treat Americans' chronic disease burden
      and disproportionately dispense medications used by key vulnerable populations
      targeted by the program. 

PMID- 25367998
TI  - Specialty drug spending trends among Medicare and Medicare Advantage enrollees,
      2007-11.
AB  - Specialty pharmaceuticals include most injectable and biologic agents used to
      treat complex conditions such as rheumatoid arthritis, multiple sclerosis, and
      cancer. We analyzed trends in specialty drug spending among Medicare
      beneficiaries ages sixty-five and older using 2007-11 pharmacy claims data from a
      20 percent sample of Medicare beneficiaries. Annual specialty drug spending per
      beneficiary who used specialty drugs increased considerably during the study
      period, from $2,641 to $8,976. However, specialty drugs accounted for only 6.7
      percent of total drug spending per beneficiary in 2007 and 9.1 percent in 2011.
      Moreover, in 2011 cost-sharing reductions under the Affordable Care Act
      significantly reduced specialty drug users' out-of-pocket burden, which decreased
      26 percent from 2010. Oral cancer agents accounted for a significant proportion
      of the increase in specialty drug spending among the study population. This
      suggests that the migration of specialty drug coverage from Medicare's Part B
      medical benefit to the Part D pharmacy benefit because of new treatment options
      may play an important role in specialty pharmacy trends. This shift is likely to
      continue as pharmaceutical innovations enable more specialty therapeutics to be
      self-administered and to be covered under the pharmacy instead of the medical
      benefit. 

PMID- 25367999
TI  - Identifying hospitals that may be at most financial risk from Medicaid
      disproportionate-share hospital payment cuts.
AB  - Medicaid disproportionate-share hospital (DSH) payments are expected to decline
      by $35.1 billion between fiscal years 2017 and 2024, a reduction brought about by
      the Affordable Care Act (ACA) and recent congressional action. DSH payments have
      long been a feature of the Medicaid program, intended to partially offset
      uncompensated care costs incurred by hospitals that treat uninsured and Medicaid
      populations. The DSH payment cuts were predicated on the expectation that the
      ACA's expansion of health insurance to millions of Americans would bring about a
      decline in many hospitals' uncompensated care costs. However, the decision of
      twenty-five states not to expand their Medicaid programs, combined with residual
      coverage gaps, may leave as many as thirty million people uninsured, and
      hospitals will bear the burden of their uncompensated care costs. We sought to
      identify the hospitals that may be the most financially vulnerable to reductions
      in Medicaid DSH payments. We found that of the 529 acute care hospitals that will
      be particularly affected by the cuts, 225 (42.5 percent) are in weak financial
      condition. Policy makers should recognize that decreases in revenue may affect
      these hospitals' ability to give vulnerable populations access to care. 

PMID- 25368000
TI  - An economic framework for preventive care advice.
AB  - Under the Affordable Care Act, preventive care measures, including vaccinations
      and screenings, recommended by the Advisory Committee on Immunization Practices
      and the US Preventive Services Task Force must be covered in full by insurance.
      These recommendations affect the cost of medical care. Yet neither organization
      explicitly incorporates measures of efficiency or cost-effectiveness in making
      its recommendations. To redress this shortcoming, we propose a decision-making
      framework for these two organizations based on the principles of economic
      efficiency. Our analysis suggests that routine use of a preventive service should
      be recommended for full insurance coverage if the service's cost-effectiveness
      exceeds a socially determined threshold. For less cost-effective services, we
      suggest that information about effectiveness and cost should be provided to
      consumers by physicians or government, but the choice of care and insurance
      coverage for care should be made by individuals. For the least cost-effective
      services, the two organizations should discourage public and private insurers
      from covering such services and report their unfavorable cost-effectiveness. 

PMID- 25368001
TI  - Bridging the gap: a community health program saved lives, then closed its doors.

PMID- 25368002
TI  - Opening a channel: finding connection and healing beyond the clinic.

PMID- 25368003
TI  - Social determinants of health and community needs: implications for health legacy
      foundations.
AB  - Mergers and acquisitions of nonprofit hospitals are on the rise. Proceeds from
      many of these transactions will endow new health legacy foundations (HLFs). These
      philanthropic entities have substantial potential for charitable investment in US
      communities. Research indicates that the greatest improvements in population
      health can be achieved by addressing underlying social factors. Determining
      whether communities served by HLFs are characterized by poor social determinants
      of health would provide new information for developing effective grant-making
      strategies. Our study compared socioeconomic, demographic, and health care access
      indicators in HLF versus non-HLF counties. Compared with non-HLF counties, HLF
      counties had significantly higher proportions of racial minorities and multiple
      socioeconomic factors that rendered them more vulnerable to health disparities
      and poor health. However, HLF counties had better access to health care. These
      findings have direct implications for HLF leadership, planning, and grant making.

PMID- 25368005
TI  - High administrative costs at US hospitals.

PMID- 25368006
TI  - High administrative costs: the authors reply.

PMID- 25368007
TI  - Price transparency in medical imaging.

PMID- 25368008
TI  - Price transparency: the author replies.

PMID- 25368009
TI  - For-profit dialysis providers.

PMID- 25368010
TI  - For-profit dialysis: the authors reply.

PMID- 25368011
TI  - PARP inhibitors for chemoprevention--letter.

PMID- 25368012
TI  - PARP inhibitors for chemoprevention--reply.

PMID- 25368013
TI  - How to make a heart valve: from embryonic development to bioengineering of living
      valve substitutes.
AB  - Cardiac valve disease is a significant cause of ill health and death worldwide,
      and valve replacement remains one of the most common cardiac interventions in
      high-income economies. Despite major advances in surgical treatment, long-term
      therapy remains inadequate because none of the current valve substitutes have the
      potential for remodeling, regeneration, and growth of native structures. Valve
      development is coordinated by a complex interplay of signaling pathways and
      environmental cues that cause disease when perturbed. Cardiac valves develop from
      endocardial cushions that become populated by valve precursor mesenchyme formed
      by an epithelial-mesenchymal transition (EMT). The mesenchymal precursors,
      subsequently, undergo directed growth, characterized by cellular
      compartmentalization and layering of a structured extracellular matrix (ECM).
      Knowledge gained from research into the development of cardiac valves is driving
      exploration into valve biomechanics and tissue engineering directed at creating
      novel valve substitutes endowed with native form and function. 

PMID- 25368014
TI  - Induced pluripotent stem cells in dermatology: potentials, advances, and
      limitations.
AB  - The discovery of methods for reprogramming adult somatic cells into induced
      pluripotent stem cells (iPSCs) has raised the possibility of producing truly
      personalized treatment options for numerous diseases. Similar to embryonic stem
      cells (ESCs), iPSCs can give rise to any cell type in the body and are amenable
      to genetic correction by homologous recombination. These ESC properties of iPSCs
      allow for the development of permanent corrective therapies for many currently
      incurable disorders, including inherited skin diseases, without using embryonic
      tissues or oocytes. Here, we review recent progress and limitations of iPSC
      research with a focus on clinical applications of iPSCs and using iPSCs to model
      human diseases for drug discovery in the field of dermatology. 

PMID- 25368016
TI  - Fungal vaccines and immunotherapeutics.
AB  - Concomitant with the increased prevalence of immunocompromised persons, invasive
      fungal infections have become considerably more frequent in the last 50 years.
      High mortality rates caused by invasive mycoses and high morbidity because of
      intractable mucosal infections have created an unmet need for innovative
      prophylactic and therapeutic strategies against fungal pathogens. Several
      immunotherapeutics and vaccines are in development to address this need, although
      one has yet to reach the clinic. This review focuses on past and current
      immunotherapeutic and vaccine strategies being tested to either prevent or treat
      fungal infections, as well as the challenges associated with their development. 

PMID- 25368015
TI  - Desmosomes: regulators of cellular signaling and adhesion in epidermal health and
      disease.
AB  - Desmosomes are intercellular junctions that mediate cell-cell adhesion and anchor
      the intermediate filament network to the plasma membrane, providing mechanical
      resilience to tissues such as the epidermis and heart. In addition to their
      critical roles in adhesion, desmosomal proteins are emerging as mediators of cell
      signaling important for proper cell and tissue functions. In this review we
      highlight what is known about desmosomal proteins regulating adhesion and
      signaling in healthy skin-in morphogenesis, differentiation and homeostasis,
      wound healing, and protection against environmental damage. We also discuss how
      human diseases that target desmosome molecules directly or interfere indirectly
      with these mechanical and signaling functions to contribute to pathogenesis. 

PMID- 25368017
TI  - Antifungal clinical trials and guidelines: what we know and do not know.
AB  - For over the last three decades, extensive testing of antifungal compounds in
      clinical trials has been essential to the development of treatment guidelines for
      the most common invasive fungal infections, including cryptococcosis,
      candidiasis, aspergillosis, and the endemic fungi. These guidelines have greatly
      helped guide clinicians in the management of these complicated diseases. The data
      on which most of these guidelines are based are among the most widely recognized
      and cited clinical trials comparing antimicrobial agents. Unfortunately, there
      are many unanswered questions with respect to the diagnosis and treatment of
      these emerging disorders. Regarding treatment, there is a need for more
      clinically effective and less toxic agents. The current armamentarium of
      antifungal agents represents important progress over gold standard agents such as
      amphotericin B, but there is much progress to be made. With respect to
      diagnostics, mycology has generally lagged behind other disciplines in
      microbiology, as there are very few rapid, sensitive, specific, and point-of-care
      diagnostics. The ability to implement therapies for at-risk patients based on
      positive early diagnostic signals would greatly enhance the ability to intervene
      with appropriate antifungal therapy in a more targeted and specific manner. This
      article will review some of the major advances, as well as significant challenges
      that remain in the management of invasive mycoses. 

PMID- 25368018
TI  - Hepatitis D virus coinfection and superinfection.
AB  - HDV is a defective RNA pathogen requiring the simultaneous presence of HBV to
      complete its life cycle. Two major specific patterns of infection have been
      described: the coinfection with HDV and HBV of a susceptible, anti-HBs-negative
      individual, or the HDV superinfection of a chronic HBV carrier. Coinfection
      mostly leads to the eradication of both agents, whereas the majority of patients
      with HDV superinfection evolve to chronic HDV infection and hepatitis. Chronic
      HDV infection worsens the preexisting HBV-related liver damage. HDV-associated
      chronic liver disease (chronic hepatitis D) is characterized by necroinflammation
      and the relentless deposition of collagen culminating, within a few decades, into
      the development of cirrhosis and hepatocellular carcinoma. 

PMID- 25368019
TI  - Rhabdomyosarcoma: current challenges and their implications for developing
      therapies.
AB  - Rhabdomyosarcoma (RMS) represents a rare, heterogeneous group of mesodermal
      malignancies with skeletal muscle differentiation. One major subgroup of RMS
      tumors (so-called "fusion-positive" tumors) carries exclusive chromosomal
      translocations that join the DNA-binding domain of the PAX3 or PAX7 gene to the
      transactivation domain of the FOXO1 (previously known as FKHR) gene. Fusion
      negative RMS represents a heterogeneous spectrum of tumors with frequent RAS
      pathway activation. Overtly metastatic disease at diagnosis is more frequently
      found in individuals with fusion-positive than in those with fusion-negative
      tumors. RMS is the most common pediatric soft-tissue sarcoma, and approximately
      60% of all children and adolescents diagnosed with RMS are cured by currently
      available multimodal therapies. However, a curative outcome is achieved in <30%
      of high-risk individuals with RMS, including all those diagnosed as adults, those
      diagnosed with fusion-positive tumors during childhood (including metastatic and
      nonmetastatic tumors), and those diagnosed with metastatic disease during
      childhood (including fusion-positive and fusion-negative tumors). This white
      paper outlines current challenges in RMS research and their implications for
      developing more effective therapies. Urgent clinical problems include local
      control, systemic disease, need for improved risk stratification, and
      characterization of differences in disease course in children and adults.
      Biological challenges include definition of the cellular functions of PAX-FOXO1
      fusion proteins, clarification of disease heterogeneity, elucidation of the
      cellular origins of RMS, delineation of the tumor microenvironment, and
      identification of means for rational selection and testing of new combination
      therapies. To streamline future therapeutic developments, it will be critical to
      improve access to fresh tumor tissue for research purposes, consider alternative
      trial designs to optimize early clinical testing of candidate drugs, coalesce
      advocacy efforts to garner public and industry support, and facilitate
      collaborative efforts between academia and industry. 

PMID- 25368020
TI  - Targeting of miR34a-NOTCH1 axis reduced breast cancer stemness and
      chemoresistance.
AB  - Human breast cancers include cancer stem cell populations as well as
      nontumorigenic cancer cells. Breast cancer stem cells have self-renewal
      capability and are resistant to conventional chemotherapy. miRNAs regulate the
      expression of many target genes; therefore, dysregulation of miRNAs has been
      associated with the pathogenesis of human diseases, including cancer. However, a
      role for miRNA dysregulation in stemness and drug resistance has yet to be
      identified. Members of the miR34 family are reportedly tumor-suppressor miRNAs
      and are associated with various human cancers. Our results confirm that miR34a
      expression was downregulated in MCF7/ADR cells compared with MCF7 cells. We
      hypothesized that this reduction was due to the p53 (TP53) mutation in MCF7/ADR
      cells. In this study, we found that primary and mature miR34a were suppressed by
      treatment with p53 RNAi or the dominant-negative p53 mutant in MCF7 cells.
      Ectopic miR34a expression reduced cancer stem cell properties and increased
      sensitivity to doxorubicin treatment by directly targeting NOTCH1. Furthermore,
      tumors from nude mice treated with miR34a were significantly smaller compared
      with those of mice treated with control lentivirus. Our research suggests that
      the ectopic expression of miR34a represents a novel therapeutic approach in
      chemoresistant breast cancer treatment.

PMID- 25368021
TI  - Twist1 is a key regulator of cancer-associated fibroblasts.
AB  - Cancer-associated fibroblasts (CAF) are key contributors to malignant
      progression, but their critical regulators remain largely unknown. In this study,
      we examined the role of Twist1, a central regulator of epithelial-mesenchymal
      transition in carcinoma cells, in the transdifferentiation of normal quiescent
      fibroblasts to CAF and we defined its upstream controls and downstream effectors.
      Primary human gastric fibroblast and CAF cultures were established from
      gastrectomy specimens and validated as nontumor cells by somatic mutation
      analyses. In these cultures, exposure to the proinflammatory cytokine IL6
      commonly expressed in tumors was sufficient to induce Twist1 expression in normal
      fibroblasts and transdifferentiate them into CAFs via STAT3 phosphorylation. In
      xenograft models, tumor infiltration of Twist1-expressing CAFs was enhanced
      strongly by ectopic IL6 expression in gastric or breast cancer cells. We found
      that Twist1 expression was necessary and sufficient for CAF transdifferentiation.
      Enforced expression of Twist1 in normal fibroblasts was also sufficient to drive
      CAF marker expression and malignant character in gastric cancer cells both in
      vitro and in vivo. Conversely, silencing the expression of Twist1 in CAFs
      abrogated their tumor-promoting properties. Downstream of Twist1, we defined the
      chemokine CXCL12 as a transcriptional target. Clinically, CXCL12 and Twist1
      expression were correlated in CAFs present in gastric tumor specimens. Finally,
      ectopic expression of Twist1 in normal fibroblasts suppressed premature
      senescence, whereas Twist1 attenuation accelerated senescence in CAFs. Our
      findings define Twist1 as a compelling target to deprogram the tumor-supporting
      features of the cancer microenvironment.

PMID- 25368022
TI  - ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells.
AB  - Cancer stem cells (CSC) are thought to play a major role in the development and
      metastatic progression of pancreatic ductal adenocarcinoma (PDAC), one of the
      deadliest solid tumors. Likewise, the tumor microenvironment contributes critical
      support in this setting, including from tumor stromal cells and tumor-associated
      macrophages (TAM) that contribute structural and paracrine-mediated supports,
      respectively. Here, we show that TAMs secrete the IFN-stimulated factor ISG15,
      which enhances CSC phenotypes in PDAC in vitro and in vivo. ISG15 was
      preferentially and highly expressed by TAM present in primary PDAC tumors
      resected from patients. ISG15 was secreted by macrophages in response to
      secretion of IFNbeta by CSC, thereby reinforcing CSC self-renewal, invasive
      capacity, and tumorigenic potential. Overall, our work demonstrates that ISG15 is
      a previously unrecognized support factor for CSC in the PDAC microenvironment
      with a key role in pathogenesis and progression.

PMID- 25368023
TI  - IgG receptor FcgammaRIIB plays a key role in obesity-induced hypertension.
AB  - There is a well-recognized association between obesity, inflammation, and
      hypertension. Why obesity causes hypertension is poorly understood. We previously
      demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces
      hypertension that is related to NO deficiency. Our prior work in cultured
      endothelial cells identified the Fcgamma receptor IIB (FcgammaRIIB) as the
      receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing
      known associations between CRP and obesity and hypertension in humans, in the
      present study we tested the hypothesis that FcgammaRIIB plays a role in obesity
      induced hypertension in mice. Using radiotelemetry, we first demonstrated that
      the hypertension observed in transgenic mouse-CRP is mediated by the receptor,
      indicating that FcgammaRIIB is capable of modifying blood pressure. We then
      discovered in a model of diet-induced obesity yielding equal adiposity in all
      study groups that whereas FcgammaRIIB(+/+) mice developed obesity-induced
      hypertension, FcgammaRIIB(-/-) mice were fully protected. Levels of CRP, the
      related pentraxin serum amyloid P component which is the CRP-equivalent in mice,
      and total IgG were unaltered by diet-induced obesity; FcgammaRIIB expression in
      endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice
      had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase
      in cultured endothelial cells, and this was an FcgammaRIIB-dependent process.
      Thus, we have identified a novel role for FcgammaRIIB in the pathogenesis of
      obesity-induced hypertension, independent of processes regulating adiposity, and
      it may entail an IgG-induced attenuation of endothelial NO synthase function.
      Approaches targeting FcgammaRIIB may potentially offer new means to treat
      hypertension in obese individuals. 

PMID- 25368025
TI  - Acute exertion elicits a H2O2-dependent vasodilator mechanism in the
      microvasculature of exercise-trained but not sedentary adults.
AB  - Brachial artery flow-mediated vasodilation in exercise-trained (ET) individuals
      is maintained after a single bout of heavy resistance exercise compared with
      sedentary individuals. The purpose of this study was to determine whether
      vasodilation is also maintained in the microcirculation of ET individuals. A
      total of 51 sedentary and ET individuals underwent gluteal subcutaneous fat
      biopsy before and after performing a single bout of leg press exercise. Adipose
      arterioles were cannulated in an organ bath, and vasodilation to acetylcholine
      was assessed+/-the endothelial nitric oxide inhibitorl-NG-nitroarginine methyl
      ester, the cyclooxygenase inhibitor indomethacin, or the hydrogen peroxide
      scavenger polyethylene glycol catalase. Separate vessels (isolated from the same
      groups) were exposed to an intraluminal pressure of 150 mm Hg for 30 minutes to
      mimic the pressor response, which occurs with isometric exercise. Vasodilation to
      acetylcholine was reduced in microvessels from sedentary subjects after either a
      single weight lifting session or exposure to increased intraluminal pressure,
      whereas microvessels from ET individuals maintained acetylcholine-mediated
      vasodilation. Before weight lifting, vasodilation of microvessels from ET
      individuals was reduced in the presence of l-NG-nitroarginine methyl ester and
      indomethacin. After weight lifting or exposure to increased intraluminal
      pressure, polyethylene glycol catalase significantly reduced vasodilation,
      whereas l-NG-nitroarginine methyl ester and indomethacin had no effect. These
      results indicate that (1) endothelium-dependent vasodilation in the
      microvasculature is maintained after heavy resistance exercise in ET individuals
      but not in sedentary subjects and that (2) high pressure alone or during weight
      lifting may induce a mechanistic switch in the microvasculature to favor hydrogen
      peroxide as the vasoactive mediator of dilation. 

PMID- 25368024
TI  - Variants in striatin gene are associated with salt-sensitive blood pressure in
      mice and humans.
AB  - Striatin is a novel protein that interacts with steroid receptors and modifies
      rapid, nongenomic activity in vitro. We tested the hypothesis that striatin would
      in turn affect mineralocorticoid receptor function and consequently sodium,
      water, and blood pressure homeostasis in an animal model. We evaluated salt
      sensitivity of blood pressure in novel striatin heterozygote knockout mice.
      Compared with wild type, striatin heterozygote exhibited a significant increase
      in blood pressure when sodium intake was increased from restricted (0.03%) to
      liberal (1.6%) sodium. Furthermore, renal expression of mineralocorticoid
      receptor and its genomic downstream targets serum/glucocorticoid-regulated kinase
      1, and epithelial sodium channel was increased in striatin heterozygote versus
      wild-type mice on liberal sodium intake while the pAkt/Akt ratio, readout of
      mineralocorticoid receptor's rapid, nongenomic pathway, was reduced. To determine
      the potential clinical relevance of these findings, we tested the association
      between single nucleotide polymorphic variants of striatin gene and salt
      sensitivity of blood pressure in 366 white hypertensive subjects. HapMap-derived
      tagging single nucleotide polymorphisms identified an association of rs2540923
      with salt sensitivity of blood pressure (odds ratio, 6.25; 95% confidence
      interval, 1.7-20; P=0.01). These data provide the first in vivo evidence in
      humans and rodents that associates striatin with markers of mineralocorticoid
      receptor activity. The data also support the hypothesis that the rapid,
      nongenomic mineralocorticoid receptor pathway (mediated via striatin) has a role
      in modulating the interaction between salt intake and blood pressure. 

PMID- 25368026
TI  - Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist
      treatment in cardiac and renal diseases.

PMID- 25368027
TI  - Effect of dipeptidyl peptidase 4 inhibition on arterial blood pressure is context
      dependent.
AB  - Because the effects of dipeptidyl peptidase 4 (DPP4) inhibitors on blood pressure
      are controversial, we examined the long-term effects of sitagliptin (80 mg/kg per
      day) on blood pressure (radiotelemetry) in spontaneously hypertensive rats (SHR),
      Wistar-Kyoto rats, and Zucker Diabetic-Sprague Dawley rats (metabolic syndrome
      model). In SHR, chronic (3 weeks) sitagliptin significantly increased systolic,
      mean, and diastolic blood pressures by 10.3, 9.2, and 7.9 mm Hg, respectively, a
      response abolished by coadministration of BIBP3226 (2 mg/kg per day; selective Y1
      receptor antagonist). Sitagliptin also significantly increased blood pressure in
      SHR treated with hydralazine (vasodilator; 25 mg/kg per day) or enalapril
      (angiotensin-converting enzyme inhibitor; 10 mg/kg per day). In Wistar-Kyoto
      rats, chronic sitagliptin slightly decreased systolic, mean, and diastolic blood
      pressures (-1.8, -1.1, and -0.4 mm Hg, respectively). In Zucker Diabetic-Sprague
      Dawley rats, chronic sitagliptin decreased systolic, mean, and diastolic blood
      pressures by -7.7, -5.8, and -4.3 mm Hg, respectively, and did not alter the
      antihypertensive effects of chronic enalapril. Because DPP4 inhibitors impair the
      metabolism of neuropeptide Y1-36 (NPY1-36; Y1-receptor agonist) and glucagon-like
      peptide (GLP)-1(7-36)NH2 (GLP-1 receptor agonist), we examined renovascular
      responses to NPY1-36 and GLP-1(7-36)NH2 in isolated perfused SHR and Zucker
      Diabetic-Sprague Dawley kidneys pretreated with norepinephrine (to induce basal
      tone). In Zucker Diabetic-Sprague Dawley kidneys, NPY1-36 and GLP-1(7-36)NH2
      exerted little, if any, effect on renovascular tone. In contrast, in SHR kidneys,
      both NPY1-36 and GLP-1(7-36)NH2 elicited potent and efficacious vasoconstriction.
      IN CONCLUSION: (1) The effects of DPP4 inhibitors on blood pressure are context
      dependent; (2) The context-dependent effects of DPP4 inhibitors are due in part
      to differential renovascular responses to DPP4's most important substrates (NPY1
      36 and GLP-1(7-36)NH2) [corrected]; (3) Y1 receptor antagonists may prevent the
      prohypertensive and possibly augment the antihypertensive effects of DPP4
      inhibitors.

PMID- 25368029
TI  - Mineralocorticoid receptor antagonists for the treatment of hypertension and the
      metabolic syndrome.

PMID- 25368028
TI  - Aging, arterial stiffness, and hypertension.

PMID- 25368030
TI  - 17-hydroxyprogesterone caproate significantly improves clinical characteristics
      of preeclampsia in the reduced uterine perfusion pressure rat model.
AB  - Preeclampsia is characterized by increased uterine artery resistance index,
      chronic immune activation, and decreased circulating nitric oxide levels. 17
      alpha-Hydroxyprogesterone caproate (17-OHPC) is a synthetic metabolite of
      progesterone used for the prevention of recurrent preterm birth. We hypothesized
      that 17-OHPC could reduce mean arterial pressure by decreasing inflammation,
      whereas improving vasodilation by increasing nitric oxide bioavailability and
      uterine artery resistance index during late gestation in the reduced uterine
      perfusion pressure (RUPP) rat model of preeclampsia. 17-OHPC (3.32 mg/kg) was
      intraperitoneally administered on gestation day 18 into RUPP rats, carotid
      catheters inserted, and mean arterial pressure, blood, and tissues were collected
      on day 19. Mean arterial pressure in normal pregnant (NP; n=13) was 92+/-2.0 and
      increased to123+/-2.0 in RUPP (n=18; P<0.0001), which was improved to 116+/-1.5
      mm Hg in RUPP+17-OHPC (n=10; P<0.05). Circulating CD4+ T cells were 1.19%+/-1.0%
      of gated cells in NP (n=7), which increased to 8.52%+/-2.4% in RUPP rats (n=10;
      P<0.05) but was reduced to 2.72%+/-0.87% (n=14; P<0.05) in RUPP+17-OHPC.
      Circulating nitrate/nitrite was 26.34+/-3.5 umol/L in NP (n=12) but was reduced
      to14.58+/-3.1 in RUPP rats (n=8; P=0.03) and increased to 22.69+/-1.62 in RUPP+17
      OHPC (n=7; P=0.05). Endothelial nitric oxide synthase expression was 0.65+/-0.11
      AU in NP (n=4), which decreased to 0.33+/-0.01 in RUPP rats (n=4; P=0.05) but
      increased to 0.57+/-0.01 in RUPP+17-OHPC (n=5; P=0.03). Uterine artery resistance
      index was 0.54+/-0.02 in NP (n=3), 0.78+/-0.03 in RUPP (n=4), and 0.63+/-0.038 in
      RUPP+17-OHPC (n=8; both P<0.05). Our findings demonstrate that even though
      modest, lowering blood pressure with 17-OHPC could be a viable treatment option
      for suppressing inflammation, uterine artery vasoconstriction while improving
      litter size. 

PMID- 25368032
TI  - Circulating aldosterone and natriuretic peptides in the general community:
      relationship to cardiorenal and metabolic disease.
AB  - We sought to investigate the role of aldosterone as a mediator of disease and its
      relationship with the counter-regulatory natriuretic peptide (NP) system. We
      measured plasma aldosterone (n=1674; aged>=45 years old) in a random sample of
      the general population from Olmsted County, MN. In a multivariate logistic
      regression model, aldosterone analyzed as a continuous variable was associated
      with hypertension (odds ratio [OR]=1.75; 95% confidence interval [CI]=1.57-1.96;
      P<0.0001), obesity (OR=1.34; 95% CI=1.21-1.48; P<0.0001), chronic kidney disease
      (OR=1.39; 95% CI=1.22-1.60; P<0.0001), central obesity (OR=1.47; 95% CI=1.32
      1.63; P<0.0001), metabolic syndrome (OR=1.41; 95% CI=1.26-1.58; P<0.0001), high
      triglycerides (OR=1.23; 95% CI=1.11-1.36; P<0.0001), concentric left ventricular
      hypertrophy (OR=1.22; 95% CI=1.09-1.38; P=0.0007), and atrial fibrillation
      (OR=1.24; 95% CI=1.01-1.53; P=0.04), after adjusting for age and sex. The
      associations with hypertension, central obesity, metabolic syndrome,
      triglycerides, and concentric left ventricular hypertrophy remained significant
      after further adjustment for body mass index, NPs, and renal function.
      Furthermore, aldosterone in the highest tertile correlated with lower NP levels
      and increased mortality. Importantly, most of these associations remained
      significant even after excluding subjects with aldosterone levels above the
      normal range. In conclusion, we report that aldosterone is associated with
      hypertension, chronic kidney disease, obesity, metabolic syndrome, concentric
      left ventricular hypertrophy, and lower NPs in the general community. Our data
      suggest that aldosterone, even within the normal range, may be a biomarker of
      cardiorenal and metabolic disease. Further studies are warranted to evaluate a
      therapeutic and preventive strategy to delay the onset and progression of
      disease, using mineralocorticoid antagonists or chronic NP administration in high
      risk subjects identified by plasma aldosterone. 

PMID- 25368033
TI  - NMR metabolomics of human lung tumours reveals distinct metabolic signatures for
      adenocarcinoma and squamous cell carcinoma.
AB  - Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC)
      and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this
      work, the metabolic signatures of lung carcinomas were investigated through (1)H
      NMR metabolomics, with a view to provide additional criteria for improved
      diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear
      Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and
      adjacent control tissues from 56 patients undergoing surgical excision of primary
      lung carcinomas. Multivariate modeling allowed tumour and control tissues to be
      discriminated with high accuracy (97% classification rate), mainly due to
      significant differences in the levels of 13 metabolites. Notably, the magnitude
      of those differences were clearly distinct for AdC and SqCC: major alterations in
      AdC were related to phospholipid metabolism (increased phosphocholine,
      glycerophosphocholine and phosphoethanolamine, together with decreased acetate)
      and protein catabolism (increased peptide moieties), whereas SqCC had stronger
      glycolytic and glutaminolytic profiles (negatively correlated variations in
      glucose and lactate and positively correlated increases in glutamate and
      alanine). Other tumour metabolic features were increased creatine, glutathione,
      taurine and uridine nucleotides, the first two being especially prominent in SqCC
      and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC
      profiles allowed their discrimination with a 94% classification rate, thus
      showing great potential for aiding lung tumours subtyping. Overall, this study
      has provided new, clear evidence of distinct metabolic signatures for lung AdC
      and SqCC, which can potentially impact on diagnosis and provide important leads
      for future research on novel therapeutic targets or imaging tracers. 

PMID- 25368031
TI  - Activation of D4 dopamine receptor decreases angiotensin II type 1 receptor
      expression in rat renal proximal tubule cells.
AB  - The dopaminergic and renin-angiotensin systems interact to regulate blood
      pressure. Disruption of the D4 dopamine receptor gene in mice produces
      hypertension that is associated with increased renal angiotensin type 1 (AT1)
      receptor expression. We hypothesize that the D4 receptor can inhibit AT1 receptor
      expression and function in renal proximal tubule cells from Wistar-Kyoto (WKY)
      rats, but the D4 receptor regulation of AT1 receptor is aberrant in renal
      proximal tubule cells from spontaneously hypertensive rats (SHRs). The D4
      receptor agonist, PD168077, decreased AT1 receptor protein expression in a time-
      and concentration-dependent manner in WKY cells. By contrast, in SHR cells,
      PD168077 increased AT1 receptor protein expression. The inhibitory effect of D4
      receptor on AT1 receptor expression in WKY cells was blocked by a calcium channel
      blocker, nicardipine, or calcium-free medium, indicating that calcium is involved
      in the D4 receptor-mediated signaling pathway. Angiotensin II increased Na(+)
      K(+) ATPase activity in WKY cells. Pretreatment with PD168077 decreased the
      stimulatory effect of angiotensin II on Na(+)-K(+) ATPase activity in WKY cells.
      In SHR cells, the inhibitory effect of D4 receptor on angiotensin II-mediated
      stimulation of Na(+)-K(+) ATPase activity was aberrant; pretreatment with
      PD168077 augmented the stimulatory effect of AT1 receptor on Na(+)-K(+) ATPase
      activity in SHR cells. This was confirmed in vivo; pretreatment with PD128077 for
      1 week augmented the antihypertensive and natriuretic effect of losartan in SHRs
      but not in WKY rats. We suggest that an aberrant interaction between D4 and AT1
      receptors may play a role in the abnormal regulation of sodium excretion in
      hypertension. 

PMID- 25368035
TI  - Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal
      cancer patients.
AB  - Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies
      worldwide. It is routinely cured by a 5-fluorouracil (5-FU)-based chemotherapy
      which improves outcomes in patients. We investigated the effect of single
      nucleotide polymorphisms (SNPs) in two microRNA (miRNA)-encoding genes that have
      been previously reported as important in prognosis in patients with stage III CRC
      and treated with 5-FU-based chemotherapy. Two SNPs (rs4919510 in miR-608 and
      rs213210 in miR-219-1) were genotyped in 1083 CRC patients recruited in the Czech
      Republic to evaluate their effect on clinical outcomes. Carriers of the variant T
      allele in rs213210 and receiving 5-FU chemotherapy were associated with a
      significantly worse survival [hazard ratio (HR) = 2.18; 95% confidence interval
      (CI): 1.20-3.98; adjusted P = 0.01] and an increased risk of relapse (HR = 1.94;
      95% CI: 1.16-3.25; adjusted P = 0.01). After further stratification for tumor
      grading, stage III patients carrying the G allele of rs4919510 and undergoing
      adjuvant chemotherapy were at decreased risk of relapse (HR = 0.44; 95% CI: 0.20
      0.94; adjusted P = 0.03). The present study confirms that variations in miRNA
      encoding genes may be an important factor for modulating CRC prognosis and
      predicting therapy response. 

PMID- 25368036
TI  - Chemical composition and biological activity of star anise Illicium verum
      extracts against maize weevil, Sitophilus zeamais adults.
AB  - This study aims to develop eco-friendly botanical pesticides. Dried fruits of
      star anise (Illicium verum Hook.f. (Austrobaileyales: Schisandraceae)) were
      extracted with methyl alcohol (MA), ethyl acetate (EA), and petroleum ether (PE)
      at 25 degrees C. The constituents were determined by gas chromatography-mass
      spectrometry, and the repellency and contact toxicity of the extracts against
      Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae) adults were tested.
      Forty-four compounds, whose concentrations were more than 0.2%, were separated
      and identified from the MA, EA, and PE extracts. The extraction yields of trans
      anethole, the most abundant biologically active compound in I. verum, were 9.7%,
      7.5%, and 10.1% in the MA, EA, and PE extracts, respectively. Repellency
      increased with increasing extract dose. The average repellency rate of the
      extracts against S. zeamais adults peaked at 125.79 ug/cm(2) 72 hr after
      treatment. The percentage repellency of the EA extract reached 76.9%, making it a
      class IV repellent. Contact toxicity assays showed average mortalities of 85.4%
      (MA), 94.5% (EA), and 91.1% (PE). The EA extract had the lowest median lethal
      dose, at 21.2 ug/cm(2) 72 hr after treatment. The results suggest that I. verum
      fruit extracts and trans-anethole can potentially be developed as a grain
      protectant to control stored-product insect pests. Other active constituents in
      the EA extract merit further research. 

PMID- 25368037
TI  - A taxonomic index, with names of descriptive authorities of termite genera and
      species: an accompaniment to Biology of Termites: A Modern Synthesis (Bignell DE,
      Roisin Y, Lo N, Editors. 2011. Springer, Dordrecht. 576 pp.).
AB  - Biology of Termites: A Modern Synthesis (Bignell DE, Roisin Y, Lo N, (Editors),
      Springer, Dordrecht, 576pp, ISBN 978-90-481-3976-7, e-ISBN 978-90-481-3977-4, DOI
      10.1007/978-90-481-3977-4) was published in 2011. With the agreement of the
      publishers, we give a taxonomic index of the book comprising 494 termite entries,
      103 entries of other multicellular animal species mentioned as associates or
      predators of termites, with 9 fungal, 60 protist, and 64 prokaryote identities,
      which are listed as termite symbionts (sensu stricto). In addition, we add
      descriptive authorities for living (and some fossil) termite genera and species.
      Higher taxonomic groupings for termites are indicated by 25 code numbers.
      Microorganisms (prokaryotes, protists, and fungi) are listed separately, using
      broad modern taxonomic affiliations from the contemporary literature of
      bacteriology, protozoology, and mycology. 

PMID- 25368038
TI  - Subfamily Coleoscirinae (Acari: Trombidiformes: Cunaxidae), with description of
      one new species from Pakistan.
AB  - The Coleoscirinae (Acari: Trombidiformes: Cunaxidae) from Pakistan are summarized
      in this paper. Two species of Scutascirus Den Heyer (S. pirgus Chaudhri and Akbar
      and S. tactus Chaudhri and Akbar), ten species of Coleoscirus Berlese (C. baptos
      (Chaudhri and Akbar), C. carex (Inayatullah and Shahid), C. carnus Muhammad and
      Chaudhri, C. comis Muhammad and Chaudhri, C. disparis Muhammad and Chaudhri, C.
      irroratus Muhammad and Chaudhri, C. mardi (Inatullah and Shahid), C. raviensis
      Afzal, Ashfaq and Khan, C. tobaensis Bashir, Afzal, Ashfaq, and Khan, and C.
      trudus Bashir, Afzal and Akbar), and three species of Pseudobonzia Smiley (P.
      ashfaqi Bashir, Afzal and Akbar, P. numida Chaudhri and Akbar, and P. parilus
      Chaudhri) have been previously reported. One new species of Pseudobonzia,
      Pseudobonzia bakeri sp n., is herein described and illustrated. A key to the
      genera of the subfamily and keys to the species in each genus are given to
      incorporate the new species from Pakistan. Distribution records of all known
      species in Pakistan are also given.

PMID- 25368039
TI  - Intra-puparial development of the black soldier-fly, Hermetia illucens.
AB  - The intra-puparial development of the black soldier-fly, Hermetia illucens (L.)
      (Diptera: Stratiomyidae), was studied based on 125 pupae under controlled
      conditions in laboratory. The 6(th) instar larvae were reared until they stopped
      feeding, and the prepupae were separated according to the reduction in larval
      length and degree of pigmentation and sclerotization of the cuticle. The pupal
      stage lasted eight days (192 hours). The process of pupation (larva/pupa
      apolysis) occurred in the first six hours, extroversion of the head and thoracic
      appendages took place between the ninth and 21(st) hours, and the pharate
      appeared 21 hours after completing pupation. After pupariation, four
      morphological phases of intra-puparial development were observed and described. 

PMID- 25368040
TI  - Variation in the outcomes of an ant-plant system: fire and leaf fungus infection
      reduce benefits to plants with extrafloral nectaries.
AB  - Interactions between species are evolutionary malleable and may suffer changes in
      small timescales. Environmental disturbances, such as fire, can deeply affect
      species interactions, but how they influence the outcome of a mutualistic
      interaction has yet to be studied. In order to test the hypothesis that an
      environmental disturbance, in this case fire, may produce differences in the
      outcome of the association of ants with the extrafloral-nectaries-bearing plant
      Qualea multiflora Mart. (Myrtales: Vochysiaceae), a previous study was
      replicated, but this time after fire incidence, at the same study site and with
      the same plant species. Eight ant species visited Q. multiflora, and the most
      abundant genera were Crematogaster, Cephalotes, and Camponotus. Herbivores were
      found in branches with and without ants with no statistical difference, but
      foliar herbivory was always higher in branchs where ants were absent. Leaves were
      infested by fungi, and fungi spots were higher in branches where ants were
      present. Compared to the previous study, it was clearly observed that ant
      benefits to Q. multiflora varied over time. The most common ant species still
      protected leaves against chewing herbivores, but a new kind of leaf damage
      appeared, namely fungi spots. Data also support that ants may be acting as
      vectors of fungi spores on plants, as ant visited branches had higher fungus
      incidence than non-visited branches. Fire is a major source of disturbance in
      tropical savannas, and we suggest that it can cause strong variation in the
      outcomes of interactions between ants and plants with extrafloral nectaries in
      the Brazilian tropical savanna. 

PMID- 25368041
TI  - Preference-performance linkage in the diamondback moth, Plutella xylostella, and
      implications for its management.
AB  - Host plants affect development, survival, and reproduction of phytophagous
      insects. In the case of holometabolous species, whose larvae have little mobility
      to find a host plant, the ability of females to discriminate hosts on the basis
      of their nutritional quality may be an important factor determining insect
      performance. The preference-performance correlation hypothesis states that
      females will choose to lay their eggs on host plants that provide the best
      offspring performance. The effects of three cultivated and two wild brassicas
      (Brassicales: Brassicaceae) on the biology of the diamondback moth, Plutella
      xylostella L. (Lepidoptera: Plutellidae), an important pest of brassicas, were
      investigated. Based on these data, the preference-performance correlation
      hypothesis was tested. The results allowed the discussion of the possible role of
      wild brassicas on population dynamics of the pest. The life table parameters net
      reproduction rate and intrinsic rate of increase were used as indicatives of
      insect performance because they provide a detailed description of the
      survivorship, development, and reproduction of a population. Development,
      survival, and reproduction were affected by the cultivated and wild brassicas.
      Both net reproduction rate and intrinsic rate of increase were lower in
      individuals fed on wild brassicas, which indicates that brassicas are not
      nutritionally suitable for P. xylostella. Nevertheless, females showed no
      oviposition preference among host plants. The results showed that host plant
      quality might not be the only factor determining host selection by female P.
      xylostella. Results also suggest that wild brassicas may serve as a refuge for P.
      xylostella, favoring pest survival when crops are disturbed by insecticide
      application, irrigation, or ploughing. 

PMID- 25368042
TI  - A new species of Labiobaetis (Ephemeroptera: Baetidae) from the southern Western
      Ghats in India, with comments on the taxonomic status of Labiobaetis.
AB  - A new species of Labiobaetis Novikova & Kluge, 1987, Labiobaetis soldani sp.
      nov., is described from the larvae and reared male and female imagoes from Gadana
      River in the southern Western Ghats in India. Brief ecological notes are
      appended. The taxonomic status of Labiobaetis is commented on in light of the
      morphological traits of the larvae and associated imagoes. 

PMID- 25368043
TI  - Targeting the diuretic hormone receptor to control the cotton leafworm,
      Spodoptera littoralis.
AB  - The cotton leafworm, Spodoptera littoralis Boisduval (Lepidoptera: Noctuidae), is
      one of the most devastating pests of crops worldwide. Several types of treatments
      have been used against this pest, but many of them failed because of the rapid
      development of genetic resistance in the different insect populations. G protein
      coupled receptors have vital functions in most organisms, including insects;
      thus, they are appealing targets for species-specific pest control strategies.
      Among the insect G protein coupled receptors, the diuretic hormone receptors have
      several key roles in development and metabolism, but their importance in vivo and
      their potential role as targets of novel pest control strategies are largely
      unexplored. With the goal of using DHR genes as targets to control S. littoralis,
      we cloned a corticotropin-releasing factor-like binding receptor in this species
      and expressed the corresponding dsRNA in tobacco plants to knock down the
      receptor activity in vivo through RNA interference. We also expressed the
      receptor in mammalian cells to study its signaling pathways. The results indicate
      that this diuretic hormone receptor gene has vital roles in S. littoralis and
      represents an excellent molecular target to protect agriculturally-important
      plants from this pest. 

PMID- 25368044
TI  - Development of a spatially targeted field sampling technique for the southern
      cattle tick, Rhipicephalus microplus, by mapping white-tailed deer, Odocoileus
      virginianus, habitat in South Texas.
AB  - The objective of our study was to determine whether satellite remote sensed data
      could be used to identify white-tailed deer, Odocoileus virginianus (Zimmerman)
      (Artiodactyla: Cervidae), habitat and target locations for sampling free-living
      larvae of the southern cattle tick, Rhipicephalus (Boophilus) microplus
      (Canestrini) (Ixodida: Ixodidae) in South Texas. Two methods for mapping white
      tailed deer habitat were used, an object-oriented method to identify closed
      canopies and waterways for deer movement and two vegetation indices: the
      Normalized Difference Vegetation Index and the Modified Soil Adjusted Vegetation
      Index to identify forage for deer. These two data sets of favorable white-tailed
      deer habitat were combined within a geographic information system to identify
      locations for sampling ticks. Larvae of R. (B.) microplus, were sampled in Zapata
      County, Texas, by walking transects with attached flannel panels to jeans.
      Although the data set and sampling period were limited, data analysis
      demonstrated that sampling of free-living larvae of R. (B.) microplus can be
      conducted in South Texas, and larvae were most abundant in areas that harbored O.
      virginianus. Spatial analysis of satellite imagery to classify white-tailed
      deer/southern cattle tick habitat proved efficacious and may be useful in
      directing sampling activities in the field. 

PMID- 25368045
TI  - Do morphological and physiological characteristics of males of the dragonfly
      Macrothemis imitans determine the winner of territorial contests?
AB  - Males of many animal species show intraspecific disputes for mating territories
      that range from displays without physical contact to physical fights with risk of
      injury. This variation motivated the proposition of different models that suggest
      possible rules used by rivals to decide the contest winner. To evaluate those
      models, it is necessary to identify how males behave during the fight and the
      individual attributes that determine their fighting ability (resource holding
      potential). For this, males of the dragonfly Macrothemis imitans (Karsch)
      (Odonata: Libellulidae) were used to evaluate two hypotheses conditioned on the
      occurrence of physical contact during the fight: if the contests occur with
      physical contact, features related to size should determine male resource holding
      potential, and if males do not exhibit physical contact during the contests,
      features that confer greater endurance should determine resource holding
      potential. To assess these hypotheses, we collected males that had ownership of
      territories (resident males) and males that occupied the territory after we
      removed the resident males (substitute males). After the capture, the resident
      and substitute males were transferred to the laboratory for measurements of wing
      area, dry weight, thoracic muscle mass, and fat content. The results showed that
      resident males do not differ in any measured trait from substitutes. Because the
      fights occur with physical contact, it is intriguing that resident males do not
      possess higher fighting capacity than intruders. Perhaps physical contact does
      not incur high costs during the fight, and other asymmetries, such as motivation
      associated with prior residency of the disputed territory, determine the contest
      winner. 

PMID- 25368046
TI  - Behavioral and electroantennogram responses of plum curculio, Conotrachelus
      nenuphar, to selected noxious plant extracts and insecticides.
AB  - Behavioral and electroantennogram responses of plum curculio, Conotrachelus
      nenuphar (Herbst) (Coleoptera: Curculionidae), adults were tested for several
      methanolic plant extracts and organically approved insecticides. Plant extracts
      were evaluated for their potential as antifeedants or oviposition deterrents.
      These extract responses were also compared to those elicited by the non
      neurotoxic, organic irritant-insecticide kaolin clay. Both sexes of plum curculio
      exhibited antennal response as measured by electroantennogram, which ranged from
      0.2 to 1.1 mV, to plant extracts and the organic irritant/insecticide, with the
      greatest response to the extract of rough cocklebur, Xanthium strumarium L. (1.1
      mV). No choice tests were conducted to compare feeding and oviposition by plum
      curculio on untreated apples or on apples treated with one of the extracts or the
      insecticide. The insecticide pyrethrum and extracts of X. strumarium and greater
      burdock, Arctium lappa L., significantly reduced feeding. Also, pyrethrum, A.
      lappa, Humulus lupulus L. (common hop), X. strumarium, and Verbascum songaricum
      Schrenk extracts completely inhibited egg deposition. In no-choice assays, the
      effects of kaolin clay with incorporated plant extracts on plum curculio feeding
      and oviposition were monitored as complementary tests. A. lappa-kaolin, H.
      lupulus-kaolin, and X. strumarium-kaolin mixtures significantly reduced the
      feeding of plum curculio compared to the control or kaolin clay alone. Each of
      the plant extract-kaolin mixtures evaluated, with the exception of Bifora radians
      Bieberstein (wild bishop), completely inhibited plum curculio oviposition as
      compared to controls. 

PMID- 25368047
TI  - Biology and external morphology of the immature stages of the butterfly Callicore
      pygas eucale, with comments on the taxonomy of the genus Callicore (Nymphalidae:
      Biblidinae).
AB  - The biology and the external morphology of the immature stages of Callicore pygas
      eucale (Fruhstorfer, 1916) (Lepidoptera: Nymphalidae: Biblidinae) are described.
      Immatures were collected on Allophylus edulis (Radlkofer) (Sapindales:
      Sapindaceae) in Curitiba, Parana, Brazil, and reared in the laboratory.
      Morphological descriptions and illustrations are given based on observations
      through electronic, stereoscopic, and optic microscopes, the latter two attached
      to a camera lucida. Results are compared and discussed with the immature stages
      of other species of the subtribe Callicorina. Immature stages data provide
      further evidence that Callicore is paraphyletic and that generic limits within
      the Callicorina need revision. 

PMID- 25368048
TI  - A new species of the planthopper genus Conosimus associated with an endemic shrub
      in southern Spain.
AB  - The poorly-known genus Conosimus Mulsant et Rey, 1855 (Hemiptera: Fulgoroidea:
      Issidae) includes six species and is briefly reviewed. Adults and fifth instars
      of a new species, Conosimus baenai n sp., are described and compared with other
      species in the genus. The new species is associated with an endemic shrub,
      Echinospartum boissieri, in Jaen, Spain, in the south of the Iberian Peninsula,
      one of the richest botanical areas of the Mediterranean Basin.

PMID- 25368049
TI  - Nutritional performance and activity of some digestive enzymes of the cotton
      bollworm, Helicoverpa armigera, in response to seven tested bean cultivars.
AB  - Nutritional performance and activity of some digestive enzymes (protease and
      alpha-amylase) of Helicoverpa armigera Hubner (Lepidoptera: Noctuidae) in
      response to feeding on bean (Phaseolus vulgaris L. (Fabales: Fabaceae)) cultivars
      (Shokufa, Akhtar, Sayyad, Naz, Pak, Daneshkadeh, and Talash) were evaluated under
      laboratory conditions (25 +/- 1 degrees C, 65 +/- 5% RH, and a 16:8 L:D
      photoperiod). The highest and lowest respective values of approximate
      digestibility were observed when fourth, fifth, and sixth larval instar H.
      armigera were fed red kidney bean Akhtar and white kidney bean Daneshkadeh. The
      efficiency of conversion of ingested and digested food was highest when H.
      armigera was fed red kidney beans Akhtar and Naz and lowest when they were fed
      white kidney bean Pak. The highest protease activity of fifth instars was
      observed when they were fed red kidney bean Naz, and the highest amylase activity
      of fifth instars was observed when they were fed red kidney bean Sayyad. Sixth
      instar larvae that fed on red kidney bean Sayyad showed the highest protease
      activity. Larvae reared on common bean Talash and white kidney bean Pak showed
      the highest amylase activity. Among bean cultivars tested, red kidney bean Sayyad
      was the most unsuitable host for feeding H. armigera.

PMID- 25368050
TI  - Identification of suitable reference genes for gene expression studies by qRT-PCR
      in the blister beetle Mylabris cichorii.
AB  - The blister beetle Mylabris cichorii L. (Coleoptera: Meloidae) is a traditional
      medicinal insect recorded in the Chinese Pharmacopoeia. It synthesizes
      cantharidin, which kills cancer cells efficiently. Only males produce large
      amounts of cantharidin. Reference genes are required as endogenous controls for
      the analysis of differential gene expression in M. cichorii. Our study chose 10
      genes as candidate reference genes. The stability of expression of these genes
      was analyzed by quantitative PCR and determined with two algorithms, geNorm and
      Normfinder. We recommend UBE3A and RPL22e as suitable reference genes in females
      and UBE3A, TAF5, and RPL22e in males. 

PMID- 25368051
TI  - A survey of the Agrotis of Iran.
AB  - The present study reviews the genus Agrotis Ochsenheimer, 1816 (Lepidoptera:
      Noctuidae: Noctuinae) in Iran from a taxonomic and faunistic point of view. An
      identification key of external features is presented for 16 Iranian species and
      subspecies. A description of each taxon is presented based on external male and
      female genital characteristics. Diagnostic features and comparisons with the
      closest relatives are given for each species. Original combination and citation
      with the synonymy of each species or subspecies are expounded as well as their
      distribution and bionomy. Adult moths and male genitalia are illustrated. 

PMID- 25368052
TI  - A comparison of infectivity between polyhedra of the Spodoptera litura multiple
      nucleopolyhedrovirus before and after passage through the gut of the stink bug,
      Eocanthecona furcellata.
AB  - Infectivity of polyhedra of Spodoptera litura multiple nucleopolyhedrovirus
      before and after passage through the gut of the predatory stink bug, Eocanthecona
      furcellata Wolff (Hemiptera: Pentatomidae) was compared through field bioassay
      studies. Three sets of E. furcellata were used for bioassays and these were
      allowed to feed on a single meal of five third instar Oriental leaf worm,
      Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), that were infected with
      polyhedra before passage, after passage, and healthy (control) larvae 1 day prior
      to the trial. The predators were subsequently released on cabbage plants that
      were infested with 100 healthy S. litura larvae. The median lethal dose (LD50)
      and survival time (ST50) values before and after passage through the gut were not
      significantly different. Additional mortality due to virus infection increased 13
      17% before and after treatments but within these treatments the mortality did
      not vary significantly. It was concluded that E. furcellata disseminated the
      virus through their feces into the ecosystem and infectivity of the SpltMNPV was
      not altered after passage through the gut of the predator.

PMID- 25368059
TI  - A novel bioassay to evaluate the potential of Beauveria bassiana strain NI8 and
      the insect growth regulator novaluron against Lygus lineolaris on a non
      autoclaved solid artificial diet.
AB  - A non-autoclaved solid diet was used to evaluate the entomopathogenic fungus
      Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Clavicipitaceae) strain NI8
      and the insect growth regulator novaluron (Diamond(r) 0.83EC insecticide) for
      control of the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois)
      (Hemiptera: Miridae). The diet was composed of toasted wheat germ, ground lima
      bean meal, soy flour, yolk of chicken eggs, inhibitor, and agar. It was prepared
      in one step by blending the ingredients in boiling water. The diet was used to
      bioassay L. lineolaris from the second instar to the adult stage. Fourth and
      fifth instars and adults of L. lineolaris were more susceptible than second and
      third instars to infection by B. bassiana, whereas second, third, and fourth
      instars had higher mortality than fifth instars 10 days after exposure to
      novaluron. No effects on longevity were observed in adults treated with novaluron
      when compared with the control, but longevity was significantly different from
      that of adults exposed to B. bassiana. Adults of L. lineolaris were maintained
      for over a month without changing the diet. The non-autoclaved diet is semi
      liquid before it cools, which facilitates the mechanics of diet packaging similar
      to food packaging or lepidopteran diet preparation. This solid artificial diet
      for Lygus bugs provides improved research capacity for studying the ecology and
      susceptibility of Lygus spp. to a number of different control agents, including
      beneficial organisms, insect pathogens, and insecticidal toxins being developed
      for transgenic technologies. 

PMID- 25368060
TI  - Copper resistance selection and activity changes of antioxidases in the flesh fly
      Boettcherisca peregrina.
AB  - Natural populations of Boettcherisca (Sarcophaga) peregrina Robineau-Desvoidy
      (Diptera: Sarcophagidae) were maintained for 20 generations and reared either on
      unpolluted diet or on polluted diet containing copper at a median lethal
      concentration (LC50) determined every five generations. This resulted in two
      reliable strains: the relative susceptible strain (S) and the copperresistant
      strain (R). The metal accumulation, growth and development, reproduction, and
      antioxidant enzymes were analyzed in the two strains. The results showed that
      compared with the S strain, the R strain showed increased metal accumulation and
      fecundity of female adults. Regardless of whether larvae were fed on diet with or
      without Cu(2+), the R strain showed higher activity of superoxide dismutase and
      glutathione S-transferase than the S strain, although without statistical
      significance. Moreover, the activity of superoxide dismutase and glutathione S
      transferase increased when B. peregrina larvae were exposed to Cu(2+) at 100 ug/g
      but decreased when they were exposed to Cu(2+) at 800 ug/g. Larval catalase
      activity in the R strain was higher than in the S strain when larvae were fed on
      diet with or without Cu(2+), although these differences were significant only at
      the 100 ug/g concentration. Moreover, the activity of catalase decreased when
      larvae were exposed to experimental Cu(2+). Beyond all expectations, larval
      glutathione reductase activity was not significantly different between the two
      strains but changed slightly when larvae were exposed to experimental Cu(2+).
      These results indicate that copper resistance in B. peregrina larvae is mediated
      by superoxide dismutase, catalase, and glutathione S-transferase. These results
      also help in establishing a physiological link between antioxidase activity and
      the resistance level of B. peregrina to copper. 

PMID- 25368061
TI  - Effects of environmental factors and appendage injury on the wing variation in
      the cricket Velarifictorus ornatus.
AB  - The effects of environmental factors and appendage injury on the wing variation
      in Velarifictorus ornatus (Shiraki) (Orthoptera: Gryllidae) were investigated.
      The percentage of micropters was more than 95% when the nymphs were reared at
      constant photoperiods, and changing photoperiod did not affect wing variation in
      V. ornatus at 25 or 30 degrees C. In the crowding experiment, the percentage of
      macropters was only 11.2% when the nymphs were reared separately at 25 degrees C.
      In contrast, the percentage of macropters was significantly higher when the
      rearing density was increased to two nymphs per container and lower when the
      rearing density was increased to five or 10 nymphs per container. These results
      indicate that low and high rearing densities induce micropters, but intermediate
      rearing density stimulates the formation of macropters. Meanwhile, severance of
      appendages, such as antennae, femora, and tibiae, in the nymph stage exerted a
      micropterizing effect. The period sensitive to such stresses ranged from 35 to 60
      days of nymph development. 

PMID- 25368062
TI  - Effects of rearing host species on the host-feeding capacity and parasitism of
      the whitefly parasitoid Encarsia formosa.
AB  - Parasitoids of the Encarsia genus (Hymenoptera: Aphelinidae) are important
      biological control agents against whiteflies. Some of the species in this genus
      not only parasitize their hosts, but also kill them through host feeding. The
      whitefly parasitoid, Encarsia formosa Gahan, was examined to determine whether
      the rearing host species affects its subsequent host-feeding capacity and
      parasitism. E. formosa wasps were reared on Trialeurodes vaporariorum (Westwood)
      (Hemiptera: Aleyrodidae) and Bemisia tabaci (Gennadius) 'Q', and their subsequent
      host-feeding capacity and parasitism of T. vaporariorum and B. tabaci were
      examined. E. formosa reared on T. vaporariorum were significantly larger in body
      size than those reared on B. tabaci, but these wasps killed a similar number of
      whitefly nymphs by host feeding when they attacked the same host species on which
      they were reared. Regardless of the species on which it was reared, E. formosa
      fed significantly more on the B. tabaci nymphs than on the T. vaporariorum
      nymphs. The number of whitefly nymphs parasitized by E. formosa differed between
      the wasps reared on T. vaporariorum and those reared on B. tabaci depending on
      which whitefly species was offered as a host. In addition, the wasps reared on T.
      vaporariorum parasitized significantly more on T. vaporariorum than those reared
      on B. tabaci. The wasps reared on B. tabaci, however, parasitized similar numbers
      of whiteflies of both host species. The results indicated that the host-feeding
      capacity of E. formosa was affected more by the host species attacked than by the
      rearing host species, but the parasitism was affected by the host species
      attacked and the rearing host species. Generally, E. formosa reared on T.
      vaporariorum killed more T. vaporariorum nymphs by parasitism and host feeding
      than those reared on B. tabaci. Additionally, a similar number of B. tabaci
      nymphs were killed by parasitism and host feeding regardless of the rearing host
      species. Currently coexistence of B. tabaci and T. vaporariorum on vegetable
      crops usually occurs in some areas; our results may provide helpful information
      on using mass-reared parasitoids against mixed whitefly infestations in
      biological control programs. 

PMID- 25368063
TI  - The discovery of the genus Spasskia Belokobylskij, 1989 (Hymenoptera: Braconidae)
      in China, with description of a new species.
AB  - The genus Spasskia Belokobylskij, 1989 (Hymenoptera: Braconidae: Helconinae) is
      reported for the first time from China. Two species, namely Spasskia
      brevicarinata Yan et Chen sp. n.and Spasskia indica Singh, Belokobylskij et
      Chauhan, 2005 are described and illustrated. A key to the species of this genus
      is updated to include the new species. 

PMID- 25368065
TI  - Lespesia melloi sp. nov. (Diptera: Tachinidae) from Brazil, a parasitoid of
      Xanthopastis timais(Lepidoptera: Noctuidae).
AB  - A new species of the New World genus Lespesia, Lespesia melloi SP NOV: (Diptera:
      Tachinidae), is described from southeastern Brazil. The species is reported here
      as a parasitoid of Xanthopastis timais (Cramer, 1782) (Lepidoptera: Noctuidae).
      The caterpillars of this noctuid feed on leaves and bulbs of amaryllis
      (Amaryllidaceae) in Brazil. 

PMID- 25368064
TI  - Biology and demographic growth parameters of cowpea aphid (Aphis craccivora) on
      faba bean (Vicia faba) cultivars.
AB  - The performance of cowpea aphid, Aphis craccivora Koch. (Hemiptera: Aphididae),
      on five faba bean, Vicia faba L. (Fabales: Fabaceae) cultivars was evaluated.
      Colony development, biology, and demographic parameters were studied to measure
      the cowpea aphid performance. Two methods, whole plant and detached leaf, were
      used in these experiments. After 14 d , the number of apterous adult, nymphs, and
      total cowpea aphids were significantly lower in cultivar Gazira2 and highest on
      cultivar Misr1. Assuming that low aphid numbers per plant represented high
      resistance, the order of resistant cultivars was as follows: Gazira2 > Misr >
      Giza3 Improved > Goff1 > Misr1. Aphid infestation significantly inhibited plant
      growth compared with uninfested plants, as indicated by factorial analysis using
      plant height (F = 41.38, P < 0.0001). The detached-leaf biological assay showed
      that the cultivar Gazira2 was less suitable than Misr1 because it had longer
      prereproductive, reproductive, and post reproductive periods, longer total
      longevity, and lower number of progeny. Similarly, demographic parameters also
      justified the suggested lower suitability of Gazira2 compared with Misr1,
      indicated by significantly lower net reproduction rate, intrinsic rate of
      increase, finite rate of increase, but longer generation time and doubling time
      on Gazira2. It was shown that cowpea aphid performed differently on the whole
      plant as compared with detached leaves. The detached-leaf biological assay is
      recommended for future experiments because it is more accurate and efficient and
      it produces reliable data. 

PMID- 25368066
TI  - The effects of strawberry cropping practices on the strawberry tortricid
      (Lepidoptera: Tortricidae), its natural enemies, and the presence of nematodes.
AB  - Cropping practice can affect pests and natural enemies. A three-year study of the
      strawberry tortricid, Acleris comariana (Lienig and Zeller) (Lepidoptera:
      Tortricidae), its parasitoid Copidosoma aretas Walker (Hymenoptera: Encyrtidae),
      and its entomopathogenic fungi was conducted in seven pairs of organic and
      conventional farms to test the hypothesis that farming practice (organic versus
      conventional) will affect the level of pest infestation and will affect the
      natural enemies. In addition, the number of years with strawberries on the farm,
      field age, and other factors that may affect pests and their natural enemies were
      considered. Farms were characterized by their cropping practices, cropping
      history, and other parameters. Field-collected larvae were laboratory reared to
      assess mortality from parasitoids and entomopathogenic fungi. In 2010, a survey
      of nematodes was made to assess the response of an unrelated taxonomic group to
      cropping practice. 2,743 larvae were collected. Of those, 2,584 were identified
      as A. comariana. 579 A. comariana were parasitized by C. aretas and 64 A.
      comariana were parasitized by other parasitoid species. Finally, 28% of the
      larvae and pupae of A. comariana died from unknown causes. Only two of the field
      collected A. comariana larvae were infected by entomopathogenic fungi; one was
      infected by Isaria sp. and the other by Beauvaria sp. The density of A. comariana
      was on average four times lower in organic farms, which was significantly lower
      than in conventional farms. A. comariana was more dominant on conventional farms
      than on organic farms. The effect of crop age (One, two, or three years) on A.
      comariana infestation was significant, with higher infestations in older fields.
      Crop age had no effect on A. comariana infestation in a comparison of first- and
      second-year fields in 2010. Cropping practice did not lead to significant
      differences in the level of total parasitism or in C. aretas parasitism; however,
      C. aretas contributed to a higher proportion of the parasitized larvae on
      conventional farms than on organic farms. Mortality from unknown causes of A.
      comariana was higher in organic farms than conventional farms, and unknown
      mortality was two to seven times higher in second-generation A. comariana than in
      first generation. Entomopathogenic nematodes were found on three organic farms
      and one conventional farm. Plant parasitic nematodes were found in more samples
      from conventional farms than from organic farms. The low density of A. comariana
      in organic farms exposes the specialist C. aretas to a higher risk of local
      extinction. In organic farms, where the density of A. comariana is low, other
      parasitoids may play an important role in controlling A. comariana by
      supplementing C. aretas. Other tortricid species may serve as alternative hosts
      for these other parasitoids, contributing to conserving them in the habitat. The
      higher unknown mortality of larvae from organic fields may be the result of non
      consumptive parasitoid or predator effects. This study reports an example of the
      effects of cropping practice on an insect pest, with similar effects on
      nematodes. An understanding of the responsible factors could be used to develop
      more sustainable cropping systems. 

PMID- 25368067
TI  - Seasonality in the dung beetle community in a Brazilian tropical dry forest: Do
      small changes make a difference?
AB  - Dung beetle (Coleoptera: Scarabaeoidea: Scarabaeinae) activity is influenced by
      rainfall seasonality. We hypothesized that rainfall might also play a major role
      in regulating the community structure of this group. In this study, we describe
      seasonal changes in the richness, composition, and structure of the Scarabaeinae
      community in a Brazilian tropical dry forest. A fragment of arboreal Caatinga was
      sampled using baited pitfall traps during the early dry season (EDS), late dry
      season (LDS), early wet season (EWS), and middle wet season (MWS). We compared
      the dung beetle community in each season in relationship to species richness,
      rank-dominance, curves, and composition. We collected 1352 Scarabaeinae
      individuals , belonging to 15 species. Dichotomius aff. laevicollis Felsche
      (Coleoptera: Scarabaeidae) was the dominant species, representing 73.89% of the
      individuals. There were no seasonal changes in the rank dominance curves; all had
      a single dominant species and a few species with low abundance, typical for arid
      areas. Estimated richness was highest in MWS, followed by EWS. Dry-season samples
      (EDS and LDS) had lower richness, with no significant difference between the dry
      seasons. Although species richness increased as the habitat became wetter, the
      difference between the wet and dry seasons was small, which differs completely
      from the findings of other studies in Neotropical dry forests, where almost all
      species cease activities in the dry season. Species composition changes were
      found in non-metric multidimensional scaling and sustained by analysis of
      similarity. All the seasons had pairwise differences in composition, with the
      exception of EDS and MWS, which indicates that the dung beetle community in this
      fragment requires more than three months of drought to trigger changes in species
      composition; this is probably due to small changes in the forest canopy. There
      was no difference in composition between EDS and MWS. As in other tropical dry
      forests, although to a lesser extent, the dung beetle community of this fragment
      responded to rainfall seasonality with changes in species composition and reduced
      species richness. Such responses, even to this lesser extent, may occur because
      of small changes in tree cover and minor microclimate changes. 

PMID- 25368068
TI  - Trade-offs between survival, longevity, and reproduction, and variation of
      survival tolerance in Mediterranean Bemisia tabaci after temperature stress.
AB  - The invasive Mediterranean Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae)
      has emerged as one of the most common agricultural pests in the world. In the
      present study, we examined the cross-tolerance, fitness costs, and benefits of
      thermal tolerance and the variation in the responses of life history traits after
      heat-shock selection. The results showed that survival and longevity of
      Mediterranean B. tabaci were decreased significantly after direct or cross
      temperature stress and that the number of eggs per female was not reduced
      significantly. Furthermore, heat-shock selection dramatically increased the
      survival of Mediterranean B. tabaci within two generations, and it did not
      significantly affect the egg number per female within five generations. These
      results indicated that there was a trade-off between survival, longevity, and
      reproduction in Mediterranean B. tabaci after temperature stress. The improvement
      in reproduction was costly in terms of decreased survival and longevity, and
      there was a fitness consequence to temperature stress. In addition, heat
      tolerance in Mediterranean B. tabaci increased substantially after selection by
      heat shock, indicating a considerable variation for survival tolerance in this
      species. This information could help us better understand the thermal biology of
      Mediterranean B. tabaci within the context of climate change. 

PMID- 25368069
TI  - First record of the leafhopper genus Varicopsella Hamilton, 1980 (Hemiptera:
      Cicadellidae: Macropsinae) in China, with descriptions of a new subgenus and new
      species, a checklist, and a key to species.
AB  - A new monobasic leafhopper subgenus, Varicopsella (Multispinulosa) Li, Dai, and
      Li, subgen. nov., of the subfamily Macropsinae (Hemiptera: Auchenorrhyncha:
      Membracoidea: Cicadellidae) is proposed to accommodate Varicopsella
      (Multispinulosa) hamiltoni Li, Dai, and Li, sp. nov.from Guangxi province of
      China. The new subgenus and new species are described and illustrated. They can
      be distinguished mainly by characteristics of the fore wings with two anteapical
      cells; weak dorsoventrally flattened body; aedeagal shaft with paired apical
      processes on ventral margin; and the shape of the dorsal connective. An updated
      checklist and an illustrated key for identification of the species of
      Varicopsella along with geographical distributions of the species are given. 

PMID- 25368070
TI  - Effect of temperature on the development and survival of immature stages of the
      carambola fruit fly, Bactrocera carambolae, and the Asian papaya fruit fly,
      Bactrocera papayae, reared on guava diet.
AB  - Members of the Bactrocera dorsalis Hendel (Diptera: Tephritidae) complex
      constitute well-recognized destructive pests of fruits in peninsular Thailand.
      The development and survival of immature stages of the carambola fruit fly,
      Bactrocera carambolae Drew & Hancock, and the Asian papaya fruit fly, Bactrocera
      papayae Drew & Hancock, were compared at six constant temperatures of 15, 20, 25,
      27, 30, and 35 degrees C, 70 +/- 5% relative humidity, and a photoperiod of 12:12
      (L:D). The objectives were to determine the effect of temperature on the
      developmental stages for optimizing rearing and to understand the geographical
      pattern of occurrence of these fruit fly species. A strong and positive linear
      relationship was observed between temperature and developmental rate of immature
      stages of B. carambolae. Similarly, a strong and positive linear relationship was
      observed between temperature and developmental rate of B. papayae. A temperature
      summation model was used to estimate the lower threshold temperature and the
      thermal constant. Bactrocera papayae was significantly faster in development and
      higher in survival and appeared to be better adapted to low temperatures than B.
      carambolae, as it exhibited the lowest threshold temperatures at all immature
      stages. The observed differences in response to various temperatures revealed to
      some extent the impact of temperature on these species' distribution in
      peninsular Thailand and other parts of the world. 

PMID- 25368071
TI  - Susceptibility of adults of the cerambycid beetle Hedypathes betulinus to the
      entomopathogenic fungi Beauveria bassiana, Metarhizium anisopliae, and
      Purpureocillium lilacinum.
AB  - The cerambycid beetle Hedypathes betulinus (Klug) (Coleoptera: Cerambycidae)
      causes severe damage to yerba mate plants (Ilex paraguariensis (St. Hilaire)
      (Aquifoliales: Aquifoliaceae)), which results in large losses of production. In
      this study, the pathogenicity of entomopathogenic fungi of the species Beauveria
      bassiana (Balsamo-Crivelli) Vuillemin (Hypocreales: Cordycipitaceae), Metarhizium
      anisopliae sensu lato (Metschnikoff) Sorokin (Hypocreales: Clavicipitaceae), and
      Purpureocillium lilacinum (Thom) Luangsa-ard, Hywel-Jones, Houbraken and Samson
      (Hypocreales: Ophiocordycipitaceae) on yerba mate were evaluated. Fifteen
      isolates of B. bassiana, two of M. anisopliae, and seven of P. lilacinum on H.
      betulinus adults were analyzed under laboratory conditions. The raw mortality
      rate caused by B. bassiana isolates varied from 51.1 to 86.3%, and their LT50
      values varied between 8.7 and 13.6 d. The isolates of M. anisopliae caused 69.6
      81.8% mortality, and their LT50 values varied between 7.4 and 7.9 d. In contrast,
      isolates of P. lilacinum were not pathogenic. M. anisopliae and B. bassiana
      isolates were pathogenic against H. betulinus adults, suggesting that they may be
      useful in biological control programs for insect pests of yerba mate. 

PMID- 25368072
TI  - Quantitative parameters and ecological implications of a specialized tritrophic
      interaction involving a seed-feeding tortricid, Pseudargyrotoza conwagana, a
      braconid parasitoid, Bracon otiosus, and the wild privet, Ligustrum vulgare.
AB  - Little is known about tritrophic interactions involving seed-feeding insects,
      parasitoid wasps, and wild fleshy fruits. Here, we examine relationships between
      Pseudargyrotoza conwagana (F.) (Lepidoptera: Tortricidae), Bracon otiosus
      Marshall (Hymenoptera: Braconidae), and the wild privet, Ligustrum vulgare L.
      (Lamiales: Oleaceae), after collecting fruits in a hedgerow habitat in northwest
      Spain and rearing insects indoors. No other insect species was detected in this
      trophic system. Each fruit contained one to four seeds, each infested fruit
      contained only one seed-feeding tortricid caterpillar, and each parasitized
      caterpillar was affected by a single braconid individual, i.e., B. otiosus was a
      solitary parasitoid. Almost half of the wild privet shrubs were infested by P.
      conwagana, and infestation ranged from 2 to 32% of fruits per infested shrub. The
      general effect of P.conwagana on wild privet dispersal can be considered low, as
      the overall rate of seed infestation was low (6% of seeds). The infestation rate
      was higher in wild privet shrubs with a larger number of seeds per fruit, and
      tortricid caterpillars that left the fruits successfully ate >80% of seeds. In
      total, the parasitism rate was moderate (25% of caterpillars), but varied
      considerably (0-75%) among shrubs where P. conwagana infestation was detected.
      Parasitism only occurred in shrubs showing high infestation rates (19-32%
      infested fruits), i.e., with high host densities; however, the parasitism rate
      was density-independent in these shrubs. The wild privets benefited from the
      action of B. otiosus in two ways: the tortricid caterpillar population was partly
      eliminated, and the caterpillars were prevented from eating more than one seed
      per fruit. The B. otiosus sex ratio was very balanced (1 male to 1.18 females).
      Winter diapause and protandry were prevalent in B. otiosus. 

PMID- 25368073
TI  - Inhibitory effect of gut bacteria from the Japanese honey bee, Apis cerana
      japonica, against Melissococcus plutonius, the causal agent of European foulbrood
      disease.
AB  - European foulbrood is a contagious bacterial disease of honey bee larvae. Studies
      have shown that the intestinal bacteria of insects, including honey bees, act as
      probiotic organisms. Microbial flora from the gut of the Japanese honey bee, Apis
      cerana japonica F. (Hymenoptera: Apidae), were characterized and evaluated for
      their potential to inhibit the growth of Melissococcus plutonius corrig. (ex
      White) Bailey and Collins (Lactobacillales: Enterococcaceae), the causative agent
      of European foulbrood. Analysis of 16S rRNA gene sequences from 17 bacterial
      strains isolated by using a culture-dependent method revealed that most isolates
      belonged to Bacillus, Staphylococcus, and Pantoea. The isolates were screened
      against the pathogenic bacterium M. plutonius by using an in vitro growth
      inhibition assay, and one isolate (Acja3) belonging to the genus Bacillus
      exhibited inhibitory activity against M. plutonius. In addition, in vivo feeding
      assays revealed that isolate Acja3 decreased the mortality of honey bee larvae
      infected with M plutonius, suggesting that this bacterial strain could
      potentially be used as a probiotic agent against European foulbrood. 

PMID- 25368075
TI  - Mating experience and food deprivation modulate odor preference and dispersal in
      Drosophila melanogaster males.
AB  - Rotting fruits offer all of the known resources required for the livelihood of
      Drosophila melanogaster Meigen (Diptera: Drosophilidae). During fruit
      fermentation, carbohydrates and proteins are decomposed to produce volatile
      alcohols and amines, respectively. It is hypothesized that D. melanogaster adults
      can detect these chemical cues at a distance to identify and locate the decaying
      fruits. In the present paper, we compared the olfactory responses and movement of
      male flies varying in mating status and nutritional state to methanol, ethanol,
      and ammonia sources using a glass Y-tube olfactometer. In general, ethanol vapor
      at low to moderate concentrations repelled more hungry mated males than satiated
      ones. In contrast, methanol showed little difference in the attractiveness to
      males at different nutritional states and mating status. Moreover, ammonia
      attracted more hungry mated males. The attractiveness increased almost linearly
      with ammonia concentration from lowest to highest. When ammonia and artificial
      diet were put together in the odor arm, the responses of male flies to mixed odor
      mimicked the response to ammonia. Furthermore, odorant concentration, mating
      status, and nutritional state affected the flies' dispersal. Mated and starved
      males dispersed at a higher rate than virgin and satiated ones. Thus, our results
      showed that starved, mated males increased dispersal and preferred ammonia that
      originated from protein. 

PMID- 25368076
TI  - Descriptions of six new species of Phaonia Robineau-Desvoidy (Diptera: Muscidae)
      from China.
AB  - This paper provides diagnoses and keys to species in the Phaonia fuscicoxa-group
      and the Phaonia barkama-group from China; describes six new species, namely
      Phaonia subfuscicoxa Xue and Rong, sp nov: , Phaonia hypotuberosurstyla Xue and
      Rong, sp nov: , Phaonia caesiipollinosa Xue and Rong, sp nov: , Phaonia daliensis
      Xue and Du, sp nov: , Phaonia quadratilamella Xue, sp nov: , and Phaonia
      maoershanensis Xue, sp nov: We report the distributions and provide notes on the
      affinities of known species.

PMID- 25368074
TI  - The complete mitochondrial genomes of the Fenton's wood white, Leptidea morsei,
      and the lemon emigrant, Catopsilia pomona.
AB  - The complete mitochondrial genomes of Leptidea morsei Fenton (Lepidoptera:
      Pieridae: Dis-morphiinae) and Catopsilia pomona (F.) (Lepidoptera: Pieridae:
      Coliadinae) were determined to be 15,122 and 15,142 bp in length, respectively,
      with that of L. morsei being the smallest among all known butterflies. Both
      mitogenomes contained 37 genes and an A+T-rich region, with the gene order
      identical to those of other butterflies, except for the presence of a tRNA-like
      insertion, tRNA(Leu) (UUR), in C. pomona. The nucleotide compositions of both
      genomes were higher in A and T (80.2% for L. morsei and 81.3% for C. pomona) than
      C and G; the A+T bias had a significant effect on the codon usage and the amino
      acid composition. The protein-coding genes utilized the standard mitochondrial
      start codon ATN, except the COI gene using CGA as the initiation codon, as
      reported in other butterflies. The intergenic spacer sequence between the
      tRNA(Ser) (UCN) and ND1 genes contained the ATACTAA motif. The A+T-rich region
      harbored a poly-T stretch and a conserved ATAGA motif located at the end of the
      region. In addition, there was a triplicated 23 bp repeat and a microsatellite
      like (TA)9(AT)3 element in the A+T-rich region of the L. morsei mitogenome, while
      in C. pomona, there was a duplicated 24 bp repeat element and a microsatellite
      like (TA)9 element. The phylogenetic trees of the main butterfly lineages
      (Hesperiidae, Papilionidae, Pieridae, Nymphalidae, Lycaenidae, and Riodinidae)
      were reconstructed with maximum likelihood and Bayesian inference methods based
      on the 13 concatenated nucleotide sequences of protein-coding genes, and both
      trees showed that the Pieridae family is sister to Lycaenidae. Although this
      result contradicts the traditional morphologically based views, it agrees with
      other recent studies based on mitochondrial genomic data. 

PMID- 25368077
TI  - Overview of research on Bombyx mori microRNA.
AB  - MicroRNAs (miRNAs) constitute some of the most significant regulatory factors
      involved at the post-transcriptional level after gene expression, contributing to
      the modulation of a large number of physiological processes such as development,
      metabolism, and disease occurrence. This review comprehensively and
      retrospectively explores the literature investigating silkworm, Bombyx mori L.
      (Lepidoptera: Bombicidae), miRNAs published to date, including discovery,
      identification, expression profiling analysis, target gene prediction, and the
      functional analysis of both miRNAs and their targets. It may provide experimental
      considerations and approaches for future study of miRNAs and benefit elucidation
      of the mechanisms of miRNAs involved in silkworm developmental processes and
      intracellular activities of other unknown non-coding RNAs. 

PMID- 25368079
TI  - Identification of a fourth haplotype of Bactericera cockerelli (Hemiptera:
      Triozidae) in the United States.
AB  - The potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), is a
      pest of potato and other solanaceous crops in North and Central America and New
      Zealand. Previous genotyping studies have demonstrated the presence of three
      different haplotypes of B. cockerelli in the United States corresponding to three
      geographical regions: Central, Western, and Northwestern. These studies utilized
      psyllids collected in the western and central United States between 1998 and
      2011. In an effort to further genotype potato psyllids collected in the 2012
      growing season, a fourth B. cockerelli haplotype was discovered corresponding to
      the Southwestern United States geographical region. High-resolution melting
      analyses identified this new haplotype using an amplicon generated from a portion
      of the B. cockerelli mitochondrial cytochrome c oxidase subunit I gene.
      Sequencing of this gene, as well as use of a restriction enzyme assay, confirmed
      the identification of the novel B. cockerelli haplotype in the United States. 

PMID- 25368078
TI  - Presence of Wolbachia in three hymenopteran species: Diprion pini (Hymenoptera:
      Diprionidae), Neodiprion sertifer (Hymenoptera: Diprionidae), and Dahlbominus
      fuscipennis (Hymenoptera: Eulophidae).
AB  - Sawflies are important pests of various plant species. Diprion pini (L.) and
      Neodiprion sertifer (Geoffroy) (Hymenoptera: Diprionidae) are two of the most
      important sawfly pests in Italy, and both species are parasitized by the
      hymenopteran parasitoid Dahlbominus fuscipennis (Zetterstedt). Bacterial
      endosymbionts are currently studied for their high potential in strategies of
      biocontrol in a number of insect species. In this study, we investigated the
      presence of symbiotic bacteria (Wolbachia and Cardinium) in the three species of
      hymenoptera mentioned earlier, both in wild and laboratory populations. Although
      all samples were negative for the presence of Cardinium, 100% prevalence for
      Wolbachia was detected, as all examined individuals resulted to be PCR positive.
      Furthermore, 16S rDNA and ftsZ gene sequencing indicated that all individuals
      from the three hymenopteran species are infected by a single Wolbachia strain.
      Additionally, we report the presence of gynandromorphic individuals in D. pini,
      both in wild and laboratory-reared populations. Heat treatments on D. pini
      colonies removed the Wolbachia symbionts, but they also prevented the development
      of adults. 

PMID- 25368080
TI  - Patterns of diversity and abundance of carrion insect assemblages in the Natural
      Park "Hoces del Rio Riaza" (central Spain).
AB  - The patterns of diversity and abundance of the carrion insect species in the
      different habitats of the Natural Park "Hoces del Rio Riaza" (central Spain) were
      studied with the use of carrion-baited traps. Representativeness of the
      inventories was assessed with the calculation of randomized species richness
      curves and nonparametric estimators. Coleoptera families, Silphidae and
      Dermestidae, and Diptera families, Calliphoridae and Muscidae, were dominant in
      every sampling habitat, but differences in the patterns of diversity and
      abundance were found. Lusitanian oakwood and riparian forest were the most
      diverse habitats with high abundance of saprophagous species, whereas more open
      (i.e., exposed to continuous sunlight during the day) habitats showed lower
      diversity values and a different species composition and distribution of species
      abundance, favoring thermophilous species and necrophagous species with high
      tolerance to different environmental conditions. Differences in the bioclimatical
      features of the sampled habitats are suggested to explain the composition and
      diversity of the carrion insect assemblages in different environments. 

PMID- 25368081
TI  - Genomic and bioinformatic analysis of NADPH-cytochrome P450 reductase in
      Anopheles stephensi (Diptera: Culicidae).
AB  - The cytochrome P450 monooxygenase (P450) enzyme system is a major mechanism of
      xenobiotic biotransformation. The nicotinamide adenine dinucleotide phosphate
      (NADPH)-cytochrome P450 reductase (CPR) is required for transfer of electrons
      from NADPH to P450. One CPR gene was identified in the genome of the malaria
      transmitting mosquito Anopheles stephensi Liston (Diptera: Culicidae). The gene
      encodes a polypeptide containing highly conserved flavin mononucleotide-, flavin
      adenine dinucleotide-, and NADPH-binding domains, a unique characteristic of the
      reductase. Phylogenetic analysis revealed that the A. stephensi and other known
      mosquito CPRs belong to a monophyletic group distinctly separated from other
      insects in the same order, Diptera. Amino acid residues of CPRs involved in
      binding of P450 and cytochrome c are conserved between A. stephensi and the
      Norway rat Rattus norvegicus Berkenhout (Rodentia: Muridae). However, gene
      structure particularly within the coding region is evidently different between
      the two organisms. Such difference might arise during the evolution process as
      also seen in the difference of P450 families and isoforms found in these
      organisms. CPR in the mosquito A. stephensi is expected to be active and serve as
      an essential component of the P450 system. 

PMID- 25368082
TI  - Radiation-induced metabolomic changes in sterile male MUomicronnochamus
      alternatus (Coleoptera: Cerambycidae).
AB  - Radiation-induced sterile insect technique is a biologically based, environment
      friendly method for the suppression or eradication of a number of insect pests.
      Although the basic mechanisms underlying the technology have been well studied,
      little is known about the cell responses in organisms. Characterization of the
      metabolic shift associated with radiation exposure in sterile insects would be
      helpful for understanding the detailed mechanism underlying this technique and
      promote its practical application. In this article, a metabolomic study was
      performed to characterize the global metabolic changes induced by radiation using
      untreated and 40 Gy (60)Cogamma-irradiated testes of Japanese pine sawyer,
      Monochamus alternatus Hope. Differential metabolites were detected and
      tentatively identified. Many key metabolites in glycolysis and the tricarboxylic
      acid cycle, as well as most fatty and amino acids, were elevated in irradiated
      male M. alternatus, presumably resulting from depression of glycolysis and the
      tricarboxylic acid cycle, each of which are important pathways for energy
      generation Adenosine Triphosphate (ATP) in insect spermatozoa. The findings in
      this article will contribute to our knowledge of the characteristic metabolic
      changes associated with irradiation sterility and understand the molecular
      mechanisms underlying radiation-induced sterile insect technique.

PMID- 25368083
TI  - Microclimatic variation within sleeve cages used in ecological studies.
AB  - Sleeve cages for enclosing or excluding arthropods are essential components of
      field studies evaluating trophic interactions. Microclimatic variation in sleeve
      cages was evaluated to characterize its potential effects on subsequent long-term
      experiments. Two sleeve cage materials, polyester and nylon, and two cage sizes,
      400 and 6000 cm(2), were tested on eastern hemlock, Tsuga canadensis (L.)
      Carriere. Temperature and relative humidity inside and outside cages, and the
      cost and durability of the cage materials, were compared. Long-term effects of
      the sleeve cages were observed by measuring new growth on T. canadensis branches.
      The ultimate goal was to identify a material that minimizes bag-induced
      microclimatic variation. Bagged branches whose microclimates mimic those of
      surrounding unbagged branches should have minimal effects on plant growth and may
      prove ideal venues for assessing herbivore and predator behavior under natural
      conditions. No differences were found in temperature or humidity between caging
      materials. Small cages had higher average temperatures than large cages,
      especially in the winter, but this difference was confounded by the fact that
      small cages were positioned higher in trees than large cages. Differences in
      plant growth were detected. Eastern hemlock branches enclosed within polyester
      cages produced fewer new growth tips than uncaged controls. Both polyester and
      nylon cages reduced the length of new shoot growth relative to uncaged branches.
      In spite of higher costs, nylon cages were superior to polyester with respect to
      durability and ease of handling.

PMID- 25368084
TI  - Biology and ecology of Alchisme grossa in a cloud forest of the Bolivian Yungas.
AB  - Treehoppers (Membracidae) exhibit different levels of sociality, from solitary to
      presocial. Although they are one of the best biological systems to study the
      evolution of maternal care in insects, information on the biology of species in
      this group is scarce. This work describes the biology and ecology of Alchisme
      grossa (Fairmaire) (Hemiptera: Membracidae) in a rain cloud forest of Bolivia.
      This subsocial membracid utilizes two host-plant species, Brugmansia suaveolens
      (Humb. & Bonpl. ex Wild) Bercht. & J.Presl and Solanum ursinum (Rusby) (both
      Solanaceae), the first one being used during the whole year and the second one
      almost exclusively during the wet season. The development of A. grossa from egg
      to adult occurred on the plant where eggs were laid. Maternal care was observed
      during the complete nymphal development, and involved behavioral traits such as
      food facilitation and antidepredatory defense. Life cycle was longer on B.
      suaveolens during the dry season and shorter on S. ursinum during the wet season.
      Mortality was similar on both host plants during the wet season but was lower on
      B. suaveolens during the dry season. The presence of a secondary female companion
      to the egg-guarding female individual and occasional iteropary is also reported.

PMID- 25368085
TI  - Cryptotermes brevis (Isoptera: Kalotermitidae) in the Azores: lessons after 2 yr
      of monitoring in the Archipelago.
AB  - The dispersal flights of West Indian drywood termite, Cryptotermes brevis
      (Walker) (Isoptera: Kalotermitidae) were surveyed in the major cities of Azores.
      The sampling device used to estimate termite density consisted of a yellow
      adhesive trap (size 45 by 24 cm), placed with an artificial or natural light
      source in a dark attic environment. In addition, data from two other projects
      were used to improve the knowledge about the geographical distribution of the
      species. The level of infestation in the two main Azorean towns differed, with
      high levels in the houses of Angra do Heroismo, whereas in Ponta Delgada, there
      are fewer houses with high levels of infestation. The infestation in Ponta
      Delgada shows a pattern of spreading from the center outward to the city's
      periphery, whereas in Angra do Heroismo, there was a pattern of spreading outward
      from several foci. The heavy infestation observed in Angra do Heroismo and the
      clear increase of infestation levels observed from 2010 to 2011 is a reason for
      concern and calls for an urgent application of an Integrated Pest Management
      (IPM) control strategy. 

PMID- 25368086
TI  - Structural and functional characterization of the actin-1 gene promoter from the
      Antheraea pernyi (Lepidoptera: Saturniidae).
AB  - The Chinese oak silkworm, Antheraea pernyi, is an economically important insect
      of the Saturniidae family. In this study, genome walking was performed to obtain
      an A. pernyi actin promoter, which can be employed in transgenic or stable cell
      line expression systems. The putative promoter was analyzed by the online
      promoter analysis programs at the Berkeley Drosophila Genome Project and the Web
      Promoter Scan Service, which led to the recognition of several functional
      elements. With respect to these elements, a series of actin A1 promoter fragments
      with 5'-deletions were generated that were then used to construct different
      vectors expressing Green Fluorescent Protein (GFP). The plasmids were transfected
      into Sf9 cells and GFP expression was determined by observing GFP fluorescence in
      cells and by measuring GFP mRNA levels with real-time polymerase chain reaction.
      Sequence comparisons indicated that the sequence cloned from A. pernyi was the
      actin A1 promoter. The basic function of the promoter was verified by
      constructing expression vectors and observing GFP expression. In addition, real
      time polymerase chain reaction revealed a strong inhibitory element may exist
      upstream of the TATA box, which downregulated gene expression. The actin A1
      promoter is an ideal candidate for use in A. pernyi transgenic systems. 

PMID- 25368087
TI  - Biology, predation, and life table of Cydnoseius negevi and Neoseiulus barkeri
      (Acari: Phytoseiidae) on the old world date mite, Oligonychus afrasiaticus
      (Acari: Tetranychidae).
AB  - The old world date mite, Oligonychus afrasiaticus (McGregor) (Acari:
      Tetranychidae) is a severe spider mite pest of date palm in most of the Middle
      East and North Africa. Considering that nothing is known about the performance of
      phytoseiid predators against O. afrasiaticus, biology, predation, and life table
      parameters of Cydnoseius negevi (Swirski and Amitai) and Neoseiulus barkeri
      Hughes (Acari: Phytoseiidae), collected from date palm orchards, were studied
      under laboratory conditions (25, 35 degrees C and 35 +/- 10% RH) as a first step
      to understand their effectiveness against all mobile life stages of O.
      afrasiaticus. For both predators, oviposition period was significantly shorter at
      35 degrees C than at 25 degrees C. The following parameters were obtained for C.
      negevi and N. barkeri at 25 and 35 degrees C, respectively: female longevity,
      31.8, 20.1, 35.7, 27.4 d; fecundity, 21.6, 38.0, 18.8, 34.8 eggs per female;
      oviposition period, 23.9, 13.7, 25.9, 18.1 d. Total predation of C. negevi and N.
      barkeri female was 246.0, 270.0, 227.6, 205.3 prey at 25 and 35 degrees C,
      respectively. Rectal plugs were observed attached to the opisthosoma of some
      adult females of N. barkeri, which often cause the mite to stick to the surface.
      Life table parameters were estimated as net reproductive rate (R0) 10.44, 17.35,
      10.19, 13.84, intrinsic rate of increase (rm) 0.14, 0.19, 0.13, 0.16 d(-1),
      finite rate of increase (lambda) 1.15, 1.21, 1.12, 1.17 d(-1), generation time
      (T) 17.03, 15.17, 17.83, 16.61 d, doubling time (DT) 04.95, 03.64, 05.33, 04.33 d
      for C. negevi and N. barkeri at 25 and 35 degrees C, respectively. The values of
      intrinsic rate of increase and net reproductive rate were higher in C. negevi
      than N. barkeri at both temperature regimes. Therefore, it could be concluded
      that C. negevi performance was better than N. barkeri against O. afrasiaticus and
      can be considered as a valuable addition to the existing methods for spider mites
      control.

PMID- 25368088
TI  - Larvicidal efficacy of different plant parts of railway creeper, Ipomoea cairica
      Extract Against Dengue Vector Mosquitoes, Aedes albopictus (Diptera: Culicidae)
      and Aedes aegypti (Diptera: Culicidae).
AB  - Natural insecticides from plant origin against mosquito vectors have been the
      main concern for research due to their high level of eco-safety. Control of
      mosquitoes in their larval stages are an ideal method since Aedes larvae are
      aquatic, thus it is easier to deal with them in this habitat. The present study
      was specifically conducted to explore the larvicidal efficacy of different plant
      parts of Ipomoea cairica (L.) or railway creeper crude extract obtained using two
      different solvents; methanol and acetone against late third-stage larvae of Aedes
      albopictus (Skuse) and Aedes aegypti (L.) (Diptera: Culicidae). Plant materials
      of I. cairica leaf, flower, and stem were segregated, airdried, powdered, and
      extracted using Soxhlet apparatus. Larvicidal bioassays were performed by using
      World Health Organization standard larval susceptibility test method for each
      species which were conducted separately for different concentration ranging from
      10 to 450 ppm. Both acetone and methanol extracts showed 100% mortality at
      highest concentration tested (450 ppm) after 24 h of exposure. Results from
      factorial ANOVA indicated that there were significant differences in larvicidal
      effects between mosquito species, solvent used and plant parts (F=5.71, df=2,
      P<0.05). The acetone extract of I. cairica leaf showed the most effective
      larvicidal action in Ae. aegypti with LC50 of 101.94 ppm followed by Ae.
      albopictus with LC50 of 105.59 ppm compared with other fractions of I. cairica
      extract obtained from flower, stem, and when methanol are used as solvent. The
      larvae of Ae. aegypti appeared to be more susceptible to I. cairica extract with
      lower LC50 value compared with Ae. albopictus (F=8.83, df=1, P<0.05). Therefore,
      this study suggests that the acetone extract of I. cairica leaf can be considered
      as plant-derived insecticide for the control of Aedes mosquitoes. This study
      quantified the larvicidal property of I. cairica extract, providing information
      on lethal concentration that may have potential for a more eco-friendly Aedes
      mosquito control program.

PMID- 25368089
TI  - New insecticides for management of tomato yellow leaf curl, a virus vectored by
      the silverleaf whitefly, Bemisia tabaci.
AB  - Greenhouse studies using a randomized complete block design were carried out to
      evaluate the effect of six insecticides on transmission of Tomato yellow leaf
      curl virus (TYLCV) by the silverleaf whitefly, Bemisia tabaci biotype B Gennadius
      (Hemiptera: Aleyrodidae) to tomato, Lycopersicon esculentum (Miller) (Solanales:
      Solanaceae), seedlings that were inoculated with whiteflies from a TYLCV colony
      in cages 3, 7, or 14 d after treatment with insecticide. The purpose was to
      reveal differences in residual efficacy of four materials that are nearing
      registration for use on tomato-cyazypyr, flupyradifurone, pyrafluquinazon, and
      sulfoxaflor-and to compare them with two established insecticides, pymetrozine
      and a zeta-cypermethrin/bifenthrin combination. Differences in efficacy were
      expected because these six materials represent five distinct modes of action and
      both contact and systemic materials. Percentage of tomato seedlings expressing
      virus symptoms tended to be lowest in seedlings treated with flupyradifurone. The
      zeta-cypermethrin/bifenthrin insecticide demonstrated comparable efficacy to
      flupyradifurone in some trials at 3 and 7 d after treatment inoculations, but not
      the 14 d after treatment inoculation. Pyrafluquinazon was not statistically
      different from cyazypyr or sulfoxaflor in percentage of plants with virus
      symptoms in any trial. Percentage virus in the cyazypyr and sulfoxaflor
      treatments was not statistically different in the 3 and 7 d after treatment
      inoculations. Among seedlings treated with insecticide, percentage with virus
      symptoms tended to be highest in the seedlings treated with pymetrozine.

PMID- 25368090
TI  - Larval biology of anthophagous Eumaeini (Lepidoptera: Lycaenidae, Theclinae) in
      the cerrado of central Brazil.
AB  - The biology and morphology of the early stages of 22 species of Eumaeini
      (Lepidoptera: Lycaenidae, Theclinae) are presented. Observations were collected
      through the inspection of inflorescences in the field and the rearing of 214
      larvae in laboratory. Allosmaitia strophius (Godart) associated with
      Malpighiaceae species and the polyphagous Strymon mulucha (Hewitson) were the
      most frequently collected species. Detritivory was observed in two species,
      Electrostrymon endymion (F.) and Kisutam syllis (Godman & Salvin), and
      myrmecophily in four other species, A. strophius, Ministrymon azia (Hewitson),
      Parrhasius polibetes (Stoll), and S. mulucha. Cannibalism was observed in A.
      strophius; in addition, the pupa of this and of three other species produced
      audible sounds. Paiwarria aphaca (Hewitson) was highlighted because of the great
      difference observed between its first and last instars, as well as the marked
      difference between that species and the larvae of Paiwarria umbratus (Geyer)
      documented in Costa Rica. Larvae of Calycopis mimas (Godman & Salvin) displayed
      "bungee jumping" behavior when stimulated. Parasitoids (Diptera, Hymenoptera)
      attacked 21 larvae of eight species, A. strophius, K. syllis, M. azia, Pai.
      aphaca, P. polibetes, Rekoa marius (Lucas), S. mulucha, and Tmolus venustus (H.H.
      Druce). Illustrations of immatures and parasitoids are provided. 

PMID- 25368091
TI  - Seasonal dynamics of the flower head infestation of Smallanthus maculatus by two
      nonfrugivorous tephritids.
AB  - Seasonal dynamics of the capitula infested by Dictyotrypeta sp. and Rhynencina
      spilogaster (Steyskal) (Diptera: Tephritidae) was evaluated throughout the
      flowering cycle of their host plant the sunflower, Smallanthus maculatus
      (Cavanilles) Robinson (Asterales: Asteraceae). In central Veracruz, Mexico, along
      16 consecutive weeks, a total of 1,017 mature capitula were collected, recording
      the presence and abundance of immature stages (larvae and pupae) and their
      related parasitoids. Both fly species were present throughout the entire season,
      with overall infestation of 51.5% of the capitula examined. However,
      Dictyotrypeta sp. infested 11.3%, representing about one-fifth of them, and R.
      spilogaster was most abundant infesting four times as many capitula (42.9%),
      whereas both species were found together in only 2.6% of the capitula examined.
      Based on the temporal occurrence of larvae and pupae into flower heads as well as
      their associated parasitoids and times of emergence, Dictyotrypeta sp. had two
      yearly generations, and it seems that the second generation could enter a
      seasonal diapause; in contrast, R. spilogaster was a univoltine species that
      entered diapause that lasted until the next year. 

PMID- 25368092
TI  - The effects of dietary protein levels on the population growth, performance, and
      physiology of honey bee workers during early spring.
AB  - This study was conducted to investigate the effects of dietary protein levels on
      honey bee colonies, specifically the population growth, physiology, and longevity
      of honey bee workers during early spring. Diets containing four different levels
      of crude protein (25.0, 29.5, 34.0, or 38.5%) and pure pollen (control) were
      evaluated. Twenty-five colonies of honey bees with sister queens were used in the
      study. We compared the effects of the different bee diets by measuring population
      growth, emergent worker weight, midgut proteolytic enzyme activity,
      hypopharyngeal gland development, and survival. After 48 d, the cumulative number
      of workers produced by the colonies ranged from 22,420 to 29,519, providing a
      significant fit to a quadratic equation that predicts the maximum population
      growth when the diet contains 31.7% crude protein. Significantly greater emergent
      worker weight, midgut proteolytic enzyme activity, hypopharyngeal gland acini,
      and survival were observed in the colonies that were fed diets containing 34.0%
      crude protein compared with the other crude protein levels. Although higher
      emergent worker weight and survival were observed in the colonies that were fed
      the control diet, there were no significant differences between the control
      colonies and the colonies that were fed 34.0% crude protein. Based on these
      results, we concluded that a dietary crude protein content of 29.5-34.0% is
      recommended to maximize the reproduction rate of honey bee colonies in early
      spring.

PMID- 25368093
TI  - The secondary contact zone of phylogenetic lineages of the Philaenus spumarius
      (Hemiptera: Aphrophoridae: Cercopidae): an example of incomplete allopatric
      speciation.
AB  - Previous studies on the phylogeography of the meadow spittlebug Philaenus
      spumarius (L.) (Hemiptera: Aphrophoridae: Cercopidae) suggest the existence of a
      contact zone of its main phylogenetic lineages along mountain chains in Europe
      and western Asia. This study presents a detailed examination of the population
      genetics of P. spumarius within the Carpathian Mountains. The main objective was
      to determine whether the populations inhabiting that area consist of individuals
      belonging to different genetic units and whether the observed pattern could be an
      example of secondary contact zone which formed after incomplete allopatric
      speciation. Specimens from six transects across the Carpathian arc were examined.
      The mitochondrial phylogeography of the meadow spittlebug in the examined area
      clearly shows that individuals from both main clades meet and mix there.
      Representatives of all three main EF1-alpha clades were also found. The present
      distribution of the main clades with a zone of overlap along the mountain ranges
      may suggest that these phylogenetic lineages form a young hybrid zone. Moreover,
      a limited number of individuals were shown to possess heteroplasmic mitochondrial
      DNA, which gives additional support to intraspecific hybridization. P. spumarius
      could be used in future work as an excellent model species in investigating
      population genetics, intraspecific hybridization, and speciation in progress. 

PMID- 25368094
TI  - Response of olive fruit fly (Diptera: Tephritidae) to an attract-and-kill trap in
      greenhouse cage tests.
AB  - A novel attract-and-kill trap for olive fruit fly, Bactrocera oleae (Rossi)
      (Diptera: Tephritidae), was constructed with yellow corrugated plastic in an
      inverted cylindrical pan shape formed from a disk and collar. The trap components
      were tested under three greenhouse temperatures and humidities of warm, hot, and
      very hot for attractiveness to caged young or older adults. A greater proportion
      of adults regardless of age were found underneath the devices including disks,
      cylindrical pans, and pans with pheromone lures and test units of cylindrical
      pans sprayed with water, insecticidal bait spray, and with lures. The effect was
      related to lower temperatures on the underside compared with the top and the
      intolerance of the pest to heat. A circular collar added to the perimeter of the
      disk that formed the top of the inverted cylinder made the attract-and-kill trap
      more attractive to adults than the disk alone. Pheromone lures or bait sprays did
      not increase adult attraction, so were not needed for efficacy. The cylindrical
      pan was especially attractive to adults when temperatures were high by providing
      shelter from the heat. At very high temperatures, the pan became unattractive,
      possibly due to heating of the construction materials. Cylindrical pans sprayed
      with water on the underside attracted the highest number of adults especially at
      high temperatures. Greenhouse tests showed that the inverted cylindrical pan
      design has potential as an attract-and-kill device for olive fruit fly control. 

PMID- 25368095
TI  - Six new record species of whiteflies (Hemiptera: Aleyrodidae) infesting Morus
      alba in China.
AB  - To determine the species of whiteflies occurring on mulberry, Morus alba L.
      (Rosales: Moraceae) in China, we collected samples in more than 87 sites in 16
      provinces of China from 2008 to 2011. In total, 10 species, representing seven
      genera of the subfamily Aleyrodinae, were identified. Of these, six species are
      newly recorded on mulberry in China, namely, Aleuroclava ficicola Takahashi,
      Aleuroclava gordoniae (Takahashi), Aleurotrachelus camelliae (Kuwana), Bemisia
      afer (Priesner & Hosny), Bemisia tabaci Gennadius, and Pealius machili Takahashi.
      Information on the taxonomy, distribution, and host plants of the whitefly
      species found on mulberry in China, along with a brief description and
      illustrations of each species are provided. 

PMID- 25368096
TI  - Unacylated ghrelin induces oxidative stress resistance in a glucose intolerance
      and peripheral artery disease mouse model by restoring endothelial cell miR-126
      expression.
AB  - Reactive oxygen species (ROS) are crucial in long-term diabetes complications,
      including peripheral artery disease (PAD). In this study, we have investigated
      the potential clinical impact of unacylated ghrelin (UnAG) in a glucose
      intolerance and PAD mouse model. We demonstrate that UnAG is able to protect
      skeletal muscle and endothelial cells (ECs) from ROS imbalance in hind limb
      ischemia-subjected ob/ob mice. This effect translates into reductions in hind
      limb functional impairment. We show that UnAG rescues sirtuin 1 (SIRT1) activity
      and superoxide dismutase-2 (SOD-2) expression in ECs. This leads to SIRT1
      mediated p53 and histone 3 lysate 56 deacetylation and results in reduced EC
      senescence in vivo. We demonstrate, using small interfering RNA technology, that
      SIRT1 is also crucial for SOD-2 expression. UnAG also renews micro-RNA (miR)-126
      expression, resulting in the posttranscriptional regulation of vascular cell
      adhesion molecule 1 expression and a reduced number of infiltrating inflammatory
      cells in vivo. Loss-of-function experiments that target miR-126 demonstrate that
      miR-126 also controls SIRT1 and SOD-2 expression, thus confirming its role in
      driving UnAG-mediated EC protection against ROS imbalance. These results indicate
      that UnAG protects vessels from ROS imbalance in ob/ob mice by rescuing miR-126
      expression, thus emphasizing its potential clinical impact in avoiding limb loss
      in PAD. 

PMID- 25368097
TI  - High levels of pigment epithelium-derived factor in diabetes impair wound healing
      through suppression of Wnt signaling.
AB  - Diabetic foot ulcer (DFU) caused by impaired wound healing is a common vascular
      complication of diabetes. The current study revealed that plasma levels of
      pigment epithelium-derived factor (PEDF) were elevated in type 2 diabetic
      patients with DFU and in db/db mice. To test whether elevated PEDF levels
      contribute to skin wound-healing delay in diabetes, endogenous PEDF was
      neutralized with an anti-PEDF antibody in db/db mice. Our results showed that
      neutralization of PEDF accelerated wound healing, increased angiogenesis in the
      wound skin, and improved the functions and numbers of endothelial progenitor
      cells (EPCs) in the diabetic mice. Further, PEDF-deficient mice showed higher
      baseline blood flow in the skin, higher density of cutaneous microvessels,
      increased skin thickness, improved numbers and functions of circulating EPCs, and
      accelerated wound healing compared with wild-type mice. Overexpression of PEDF
      suppressed the Wnt signaling pathway in the wound skin. Lithium chloride-induced
      Wnt signaling activation downstream of the PEDF interaction site attenuated the
      inhibitory effect of PEDF on EPCs and rescued the wound-healing deficiency in
      diabetic mice. Taken together, these results suggest that elevated circulating
      PEDF levels contribute to impaired wound healing in the process of angiogenesis
      and vasculogenesis through the inhibition of Wnt/beta-catenin signaling. 

PMID- 25368098
TI  - Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian
      randomization study.
AB  - Circulating bilirubin, a natural antioxidant, is associated with decreased risk
      of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We
      performed Mendelian randomization in a prospective cohort of 3,381 participants
      free of diabetes at baseline (age 28-75 years; women 52.6%). We used rs6742078
      located in the uridine diphosphate-glucuronosyltransferase locus as an
      instrumental variable (IV) to study a potential causal effect of serum total
      bilirubin level on T2D risk. T2D developed in a total of 210 participants (6.2%)
      during a median follow-up period of 7.8 years. In adjusted analyses, rs6742078,
      which explained 19.5% of bilirubin variation, was strongly associated with total
      bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P < 1 * 10(-122))
      and was also associated with T2D risk (odds ratio [OR] 0.69 [95% CI 0.54-0.90]; P
      = 0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a
      25% (OR 0.75 [95% CI 0.62-0.92]; P = 0.004) lower risk of T2D. In Mendelian
      randomization analysis, the causal risk reduction for T2D was estimated to be 42%
      (causal OR for IV estimation per 1-SD increase in log-transformed bilirubin 0.58
      [95% CI 0.39-0.84]; P = 0.005), which was comparable to the observational
      estimate (Durbin-Wu-Hausman chi(2) test, P for difference = 0.19). These novel
      results provide evidence that an elevated bilirubin level is causally associated
      with the risk of T2D and support its role as a protective determinant. 

PMID- 25368099
TI  - Epigenetic changes in bone marrow progenitor cells influence the inflammatory
      phenotype and alter wound healing in type 2 diabetes.
AB  - Classically activated (M1) macrophages are known to play a role in the
      development of chronic inflammation associated with impaired wound healing in
      type 2 diabetes (T2D); however, the mechanism responsible for the dominant
      proinflammatory (M1) macrophage phenotype in T2D wounds is unknown. Since
      epigenetic enzymes can direct macrophage phenotypes, we assessed the role of
      histone methylation in bone marrow (BM) stem/progenitor cells in the programming
      of macrophages toward a proinflammatory phenotype. We have found that a
      repressive histone methylation mark, H3K27me3, is decreased at the promoter of
      the IL-12 gene in BM progenitors and this epigenetic signature is passed down to
      wound macrophages in a murine model of glucose intolerance (diet-induced obese).
      These epigenetically "preprogrammed" macrophages result in poised macrophages in
      peripheral tissue and negatively impact wound repair. We found that in diabetic
      conditions the H3K27 demethylase Jmjd3 drives IL-12 production in macrophages and
      that IL-12 production can be modulated by inhibiting Jmjd3. Using human T2D
      tissue and murine models, we have identified a previously unrecognized mechanism
      by which macrophages are programmed toward a proinflammatory phenotype,
      establishing a pattern of unrestrained inflammation associated with nonhealing
      wounds. Hence, histone demethylase inhibitor-based therapy may represent a novel
      treatment option for diabetic wounds. 

PMID- 25368100
TI  - Global biochemical profiling identifies beta-hydroxypyruvate as a potential
      mediator of type 2 diabetes in mice and humans.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are incretins
      secreted by respective K and L enteroendocrine cells after eating and amplify
      glucose-stimulated insulin secretion (GSIS). This amplification has been termed
      the "incretin response." To determine the role(s) of K cells for the incretin
      response and type 2 diabetes mellitus (T2DM), diphtheria toxin-expressing (DT)
      mice that specifically lack GIP-producing cells were backcrossed five to eight
      times onto the diabetogenic NONcNZO10/Ltj background. As in humans with T2DM, DT
      mice lacked an incretin response, although GLP-1 release was maintained. With
      high-fat (HF) feeding, DT mice remained lean but developed T2DM, whereas wild
      type mice developed obesity but not diabetes. Metabolomics identified
      biochemicals reflecting impaired glucose handling, insulin resistance, and
      diabetes complications in prediabetic DT/HF mice. beta-Hydroxypyruvate and
      benzoate levels were increased and decreased, respectively, suggesting beta
      hydroxypyruvate production from d-serine. In vitro, beta-hydroxypyruvate altered
      excitatory properties of myenteric neurons and reduced islet insulin content but
      not GSIS. beta-Hydroxypyruvate-to-d-serine ratios were lower in humans with
      impaired glucose tolerance compared with normal glucose tolerance and T2DM.
      Earlier human studies unmasked a neural relay that amplifies GIP-mediated insulin
      secretion in a pattern reciprocal to beta-hydroxypyruvate-to-d-serine ratios in
      all groups. Thus, K cells may maintain long-term function of neurons and beta
      cells by regulating beta-hydroxypyruvate levels. 

PMID- 25368101
TI  - Pathways targeted by antidiabetes drugs are enriched for multiple genes
      associated with type 2 diabetes risk.
AB  - Genome-wide association studies (GWAS) have uncovered >65 common variants
      associated with type 2 diabetes (T2D); however, their relevance for drug
      development is not yet clear. Of note, the first two T2D-associated loci (PPARG
      and KCNJ11/ABCC8) encode known targets of antidiabetes medications. We therefore
      tested whether other genes/pathways targeted by antidiabetes drugs are associated
      with T2D. We compiled a list of 102 genes in pathways targeted by marketed
      antidiabetic medications and applied Gene Set Enrichment Analysis (MAGENTA [Meta
      Analysis Gene-set Enrichment of variaNT Associations]) to this gene set, using
      available GWAS meta-analyses for T2D and seven quantitative glycemic traits. We
      detected a strong enrichment of drug target genes associated with T2D (P = 2 *
      10(-5); 14 potential new associations), primarily driven by insulin and
      thiazolidinedione (TZD) targets, which was replicated in an independent meta
      analysis (Metabochip). The glycemic traits yielded no enrichment. The T2D
      enrichment signal was largely due to multiple genes of modest effects (P = 4 *
      10(-4), after removing known loci), highlighting new associations for follow-up
      (ACSL1, NFKB1, SLC2A2, incretin targets). Furthermore, we found that TZD targets
      were enriched for LDL cholesterol associations, illustrating the utility of this
      approach in identifying potential side effects. These results highlight the
      potential biomedical relevance of genes revealed by GWAS and may provide new
      avenues for tailored therapy and T2D treatment design. 

PMID- 25368102
TI  - The efficacy of preoperative positron emission tomography-computed tomography
      (PET-CT) for detection of lymph node metastasis in cervical and endometrial
      cancer: clinical and pathological factors influencing it.
AB  - OBJECTIVE: We studied the diagnostic performance of (18)F-fluoro-2-deoxy-d
      glucose-positron emission tomography/computed tomography in cervical and
      endometrial cancers with particular focus on lymph node metastases. METHODS:
      Seventy patients with cervical cancer and 53 with endometrial cancer were imaged
      with (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed
      tomography before lymphadenectomy. We evaluated the diagnostic performance of
      (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography
      using the final pathological diagnoses as the golden standard. RESULTS: We
      calculated the sensitivity, specificity, positive predictive value and negative
      predictive value of (18)F-fluoro-2-deoxy-D-glucose-positron emission
      tomography/computed tomography. In cervical cancer, the results evaluated by
      cases were 33.3, 92.7, 55.6 and 83.6%, respectively. When evaluated by the area
      of lymph nodes, the results were 30.6, 98.9, 55.0 and 97.0%, respectively. As for
      endometrial cancer, the results evaluated by cases were 50.0, 93.9, 40.0 and
      95.8%, and by area of lymph nodes, 45.0, 99.4, 64.3 and 98.5%, respectively. The
      limitation of the efficacy was found out by analyzing it by the region of the
      lymph node, the size of metastatic node, the historical type of tumor in cervical
      cancer and the prevalence of lymph node metastasis. CONCLUSION: The efficacy of
      positron emission tomography/computed tomography regarding the detection of lymph
      node metastasis in cervical and endometrial cancer is not established and has
      limitations associated with the region of the lymph node, the size of metastasis
      lesion in lymph node and the pathological type of primary tumor. The indication
      for the imaging and the interpretation of the results requires consideration for
      each case by the pretest probability based on the information obtained
      preoperatively.

PMID- 25368103
TI  - Non-randomized confirmatory trial of modified radical hysterectomy for patients
      with tumor diameter 2 cm or less FIGO Stage IB1 uterine cervical cancer: Japan
      Clinical Oncology Group Study (JCOG1101).
AB  - A non-randomized confirmatory trial was started in Japan to evaluate the efficacy
      of modified radical hysterectomy in patients with tumor diameter 2 cm or less
      FIGO Stage IB1 uterine cervical cancer, for which the current standard is radical
      hysterectomy. This study began in January 2013 and a total of 240 patients will
      be accrued from 37 institutions within 3 years. The primary endpoint is 5-year
      survival. The secondary endpoints are overall survival, relapse-free survival,
      local relapse-free survival, percent completion of modified radical hysterectomy,
      percent local relapse, percent pathological parametrial involvement, days until
      self-urination and residual urine disappearance, blood loss, operation time,
      percent post-operative radiation therapy, adverse events and severe adverse
      events. This trial was registered at the UMIN Clinical Trials Registry as UMIN
      000009726 (http://www.umin.ac.jp/ctr/). 

PMID- 25368104
TI  - Glycemic targets in the second and third trimester of pregnancy for women with
      type 1 diabetes.
AB  - OBJECTIVE: To assess the relationship between second and third trimester glycemic
      control and adverse outcomes in pregnant women with type 1 diabetes, as
      uncertainty exists about optimum glycemic targets. RESEARCH DESIGN AND METHODS:
      Pregnancy outcomes were assessed prospectively in 725 women with type 1 diabetes
      from the Diabetes and Pre-eclampsia Intervention Trial. HbA1c (A1C) values at 26
      and 34 weeks' gestation were categorized into five groups, the lowest, <6.0% (42
      mmol/mol), being the reference. Average pre- and postprandial results from an
      eight-point capillary glucose profile the previous day were categorized into five
      groups, the lowest (preprandial <5.0 mmol/L and postprandial <6.0 mmol/L) being
      the reference. RESULTS: An A1C of 6.0-6.4% (42-47 mmol/mol) at 26 weeks'
      gestation was associated with a significantly increased risk of large for
      gestational age (LGA) (odds ratio 1.7 [95% CI 1.0-3.0]) and an A1C of 6.5-6.9%
      (48-52 mmol/mol) with a significantly increased risk of preterm delivery (odds
      ratio 2.5 [95% CI 1.3-4.8]), pre-eclampsia (4.3 [1.7-10.8]), need for a neonatal
      glucose infusion (2.9 [1.5-5.6]), and a composite adverse outcome (3.2 [1.3
      8.0]). These risks increased progressively with increasing A1C. Results were
      similar at 34 weeks' gestation. Glucose data showed less consistent trends,
      although the risk of a composite adverse outcome increased with preprandial
      glucose levels between 6.0 and 6.9 mmol/L at 34 weeks (3.3 [1.3-8.0]).
      CONCLUSIONS: LGA increased significantly with an A1C >=6.0 (42 mmol/mol) at 26
      and 34 weeks' gestation and with other adverse outcomes with an A1C >=6.5% (48
      mmol/mol). The data suggest that there is clinical utility in regular measurement
      of A1C during pregnancy.

PMID- 25368105
TI  - CD247, a novel T cell-derived diagnostic and prognostic biomarker for detecting
      disease progression and severity in patients with type 2 diabetes.
AB  - OBJECTIVE: We have previously shown that chronic inflammation results in
      immunosuppression associated with CD247 downregulation in T lymphocytes. Type 2
      diabetes mellitus (T2DM) is known to be associated with chronic inflammation. We
      therefore sought to examine CD247 expression levels in patients with T2DM and to
      assess whether it can serve as a diagnostic and prognostic biomarker for disease
      complications and outcomes. RESEARCH DESIGN AND METHODS: Peripheral blood samples
      from 75 T2DM patients and 40 healthy control subjects were collected and analyzed
      for the expression level of CD247 in T lymphocytes. Subjects with T2DM underwent
      a medical interview with physical examination and were followed for an additional
      average of 19.2 +/- 0.9 months to determine the occurrence of major adverse
      disease end points. The relationship between the level of CD247 expression and
      disease status at the time of blood draw and the ability of the marker to
      identify future complications was evaluated. RESULTS: We observed a significant
      reduction in CD247 expression levels in T lymphocytes of T2DM patients when
      compared with healthy volunteers. CD247 downregulation was associated with
      disease severity, complications, and the occurrence of future cardiovascular
      events, suggesting its potential use not only as a diagnostic but also as a
      prognostic biomarker. CONCLUSIONS: Our results suggest the use of CD247 as a
      biomarker in diabetic patients for evaluating the state of chronic inflammation
      that contributes to morbidity and mortality in this disease and for the
      prediction of future cardiovascular events.

PMID- 25368106
TI  - A rapid ceramide synthase activity using NBD-sphinganine and solid phase
      extraction.
AB  - Ceramides are synthesized by six mammalian ceramide synthases (CerSs), each of
      which uses fatty acyl-CoAs of different chain lengths for N-acylation of the
      sphingoid long-chain base. We now describe a rapid and reliable CerS assay that
      uses a fluorescent N-[6-[(7-nitrobenzo-2-oxa-1,3-diazol-4-yl) (NBD) sphinganine
      substrate followed by separation of the NBD-lipid substrate and products using
      solid phase extraction (SPE) C18 chromatography. SPE chromatography is a quick
      and reliable alternative to TLC, and moreover, there is no degradation of either
      NBD-sphinganine or NBD-ceramide. We have optimized the assay for use with minimal
      amounts of protein in a minimal volume. This assay will prove useful for the
      analysis of CerS activity, which is of particular importance in light of the
      growing involvement of CerS in cell regulation and in the pathology of human
      diseases. 

PMID- 25368107
TI  - Genomic variations integrated database for MUTYH-associated adenomatous
      polyposis.

PMID- 25368108
TI  - EIF4G1 is neither a strong nor a common risk factor for Parkinson's disease:
      evidence from large European cohorts.
AB  - BACKGROUND: Missense mutations in the eukaryotic translation initiation factor 4
      gamma 1 (EIF4G1) gene have previously been implicated in familial Parkinson's
      disease (PD). A large PD family with autosomal-dominant segregation showed a
      heterozygous missense mutation and additional patients were found to have unique
      sequence variants that have not been observed in controls. Subsequent studies
      have reported contradictory findings. METHODS: We assessed the relevance of
      EIF4G1 mutations in a European cohort of 2146 PD patients. Of these, 2051
      sporadic PD patients were screened for the reported p.Ala502Val and p.Arg1205His
      mutations. In addition, the complete coding region of EIF4G1 was directly
      sequenced in 95 familial PD patients with autosomal-dominant inheritance.
      Moreover, we imputed the p.Arg1205His substitution and tested for association
      with PD in the Icelandic population (93 698 samples). RESULTS: We did not observe
      the presence of the p.Ala502Val substitution in our cohort; however, the
      p.Arg1205His mutation was identified in one sporadic PD patient. The same
      mutation was also found in 76 Icelandic subjects older than 65 years using
      haplotype imputing. Only five of these subjects reported PD symptoms (OR 1.3,
      p=0.50). Thus, if causal, the p.Arg1205His EIF4G1 mutation has a low penetrance
      or a late onset manifestation. A novel variant p.Arg566Cys found in a patient
      with familial PD did not cosegregate with PD in all three affected siblings. All
      further recently published EIF4G1 mutations found in our cohort are likely to be
      benign polymorphisms. CONCLUSIONS: This is the largest genetic study of EIF4G1
      mutations in PD. Our data do not support the EIF4G1 gene as a high-risk PD locus,
      neither for the familial nor the sporadic condition. Furthermore, the
      p.Arg1205His mutation is not significantly associated with increased risk of PD
      in the Icelandic population. Therefore, caution should be exercised when
      interpreting EIF4G1 genotyping results in isolated patients and PD families. In
      summary, diagnostic testing of EIF4G1 should not be recommended in clinical
      settings.

PMID- 25368109
TI  - Immune characterization of Plasmodium falciparum parasites with a shared genetic
      signature in a region of decreasing transmission.
AB  - As the intensity of malaria transmission has declined, Plasmodium falciparum
      parasite populations have displayed decreased clonal diversity resulting from the
      emergence of many parasites with common genetic signatures (CGS). We have
      monitored such CGS parasite clusters from 2006 to 2013 in Thies, Senegal, using
      the molecular barcode. The first, and one of the largest observed clusters of CGS
      parasites, was present in 24% of clinical isolates in 2008, declined to 3.4% of
      clinical isolates in 2009, and then disappeared. To begin to explore the
      relationship between the immune responses of the population and the emergence and
      decline of specific parasite genotypes, we have determined whether antibodies to
      CGS parasites correlate with their prevalence. We measured (i) antibodies capable
      of inhibiting parasite growth in culture and (ii) antibodies recognizing the
      surfaces of infected erythrocytes (RBCs). IgG obtained from volunteers in 2009
      showed increased reactivity to the surfaces of CGS-parasitized erythrocytes over
      IgG from 2008. Since P. falciparum EMP-1 (PfEMP-1) is a major variant surface
      antigen, we used var Ups quantitative reverse transcription-PCR (qRT-PCR) and
      sequencing with degenerate DBL1alpha domain primers to characterize the var genes
      expressed by CGS parasites after short-term in vitro culture. CGS parasites show
      upregulation of UpsA var genes and 2-cysteine-containing PfEMP-1 molecules and
      express the same dominant var transcript. Our work indicates that the CGS
      parasites in this cluster express similar var genes, more than would be expected
      by chance in the population, and that there is year-to-year variation in immune
      recognition of surface antigens on CGS parasite-infected erythrocytes. This study
      lays the groundwork for detailed investigations of the mechanisms driving the
      expansion or contraction of specific parasite clones in the population. 

PMID- 25368110
TI  - Host intestinal signal-promoted biofilm dispersal induces Vibrio cholerae
      colonization.
AB  - Vibrio cholerae causes human infection through ingestion of contaminated food and
      water, leading to the devastating diarrheal disease cholera. V. cholerae forms
      matrix-encased aggregates, known as biofilms, in the native aquatic environment.
      While the formation of V. cholerae biofilms has been well studied, little is
      known about the dispersal from biofilms, particularly upon entry into the host.
      In this study, we found that the exposure of mature biofilms to physiologic
      levels of the bile salt taurocholate, a host signal for the virulence gene
      induction of V. cholerae, induces an increase in the number of detached cells
      with a concomitant decrease in biofilm mass. Scanning electron microscopy
      micrographs of biofilms exposed to taurocholate revealed an altered, perhaps
      degraded, appearance of the biofilm matrix. The inhibition of protein synthesis
      did not alter rates of detachment, suggesting that V. cholerae undergoes a
      passive dispersal. Cell-free media from taurocholate-exposed biofilms contains a
      larger amount of free polysaccharide, suggesting an abiotic degradation of
      biofilm matrix by taurocholate. Furthermore, we found that V. cholerae is only
      able to induce virulence in response to taurocholate after exit from the biofilm.
      Thus, we propose a model in which V. cholerae ingested as a biofilm has coopted
      the host-derived bile salt signal to detach from the biofilm and go on to
      activate virulence. 

PMID- 25368111
TI  - Adenovirus vector expressing Stx1/Stx2-neutralizing agent protects piglets
      infected with Escherichia coli O157:H7 against fatal systemic intoxication.
AB  - Hemolytic-uremic syndrome (HUS), caused by Shiga toxin (Stx)-producing
      Escherichia coli (STEC), remains untreatable. Production of human monoclonal
      antibodies against Stx, which are highly effective in preventing Stx sequelae in
      animal models, is languishing due to cost and logistics. We reported previously
      that the production and evaluation of a camelid heavy-chain-only VH domain (VHH)
      based neutralizing agent (VNA) targeting Stx1 and Stx2 (VNA-Stx) protected mice
      from Stx1 and Stx2 intoxication. Here we report that a single intramuscular
      (i.m.) injection of a nonreplicating adenovirus (Ad) vector carrying a secretory
      transgene of VNA-Stx (Ad/VNA-Stx) protected mice challenged with Stx2 and
      protected gnotobiotic piglets infected with STEC from fatal systemic
      intoxication. One i.m. dose of Ad/VNA-Stx prevented fatal central nervous system
      (CNS) symptoms in 9 of 10 animals when it was given to piglets 24 h after
      bacterial challenge and in 5 of 9 animals when it was given 48 h after bacterial
      challenge, just prior to the onset of CNS symptoms. All 6 placebo animals died or
      were euthanized with severe CNS symptoms. Ad/VNA-Stx treatment had no impact on
      diarrhea. In conclusion, Ad/VNA-Stx treatment is effective in protecting piglets
      from fatal Stx2-mediated CNS complications following STEC challenge. With a low
      production cost and further development, this could presumably be an effective
      treatment for patients with HUS and/or individuals at high risk of developing HUS
      due to exposure to STEC. 

PMID- 25368112
TI  - Host hydrogen rather than that produced by the pathogen is important for
      Salmonella enterica serovar Typhimurium virulence.
AB  - Salmonella enterica serovar Typhimurium utilizes molecular hydrogen as a
      substrate in various respiratory pathways, via H2-uptake enzymes termed Hya, Hyb,
      and Hyd. A different hydrogenase, the hydrogen-evolving Hyc enzyme, removes
      excess reductant during fermentative growth. Virulence phenotypes conferred by
      mutations in hyc genes, either alone or in combination with mutations in the H2
      uptake enzyme genes, are addressed. Anaerobically grown DeltahycB or DeltahycC
      single-deletion strains were more sensitive to acid than the wild-type strain,
      but the Deltahyc strains were like the virulent parent strain with respect to
      both mouse morbidity and mortality and in organ burden numbers. Even fecal
      recovery numbers for both mutant strains at several time points prior to the
      animals succumbing to salmonellosis were like those seen with the parent. Neither
      hydrogen uptake nor evolution of the gas was detected in a hydrogenase quadruple
      mutant strain containing deletions in the hya, hyb, hyd, and hyc genes. As
      previously described, a strain lacking all H2-uptake ability was severely
      attenuated in its virulence characteristics, and the quadruple-mutant strain had
      the same (greatly attenuated) phenotype. While H2 levels were greatly reduced in
      ceca of mice treated with antibiotics, both the DeltahycB and DeltahycC strains
      were still like the parent in their ability to cause typhoid salmonellosis. It
      seems that the level of H2 produced by the pathogen (through formate hydrogen
      lyase [FHL] and Hyc) is insignificant in terms of providing respiratory reductant
      to facilitate either organ colonization or contributions to gut growth leading to
      pathogenesis. 

PMID- 25368113
TI  - A replicating adenovirus capsid display recombinant elicits antibodies against
      Plasmodium falciparum sporozoites in Aotus nancymaae monkeys.
AB  - Decades of success with live adenovirus vaccines suggest that replication
      competent recombinant adenoviruses (rAds) could serve as effective vectors for
      immunization against other pathogens. To explore the potential of a live rAd
      vaccine against malaria, we prepared a viable adenovirus 5 (Ad5) recombinant that
      displays a B-cell epitope from the circumsporozoite protein (CSP) of Plasmodium
      falciparum on the virion surface. The recombinant induced P. falciparum
      sporozoite-neutralizing antibodies in mice. Human adenoviruses do not replicate
      in mice. Therefore, to examine immunogenicity in a system in which, as in humans,
      the recombinant replicates, we constructed a similar recombinant in an adenovirus
      mutant that replicates in monkey cells and immunized four Aotus nancymaae
      monkeys. The recombinant replicated in the monkeys after intratracheal
      instillation, the first demonstration of replication of human adenoviruses in New
      World monkeys. Immunization elicited antibodies both to the Plasmodium epitope
      and the Ad5 vector. Antibodies from all four monkeys recognized CSP on intact
      parasites, and plasma from one monkey neutralized sporozoites in vitro and
      conferred partial protection against P. falciparum sporozoite infection after
      passive transfer to mice. Prior enteric inoculation of two animals with
      antigenically wild-type adenovirus primed a response to the subsequent
      intratracheal inoculation, suggesting a route to optimizing performance. A
      vaccine is not yet available against P. falciparum, which induces the deadliest
      form of malaria and kills approximately one million children each year. The live
      capsid display recombinant described here may constitute an early step in a
      critically needed novel approach to malaria immunization. 

PMID- 25368114
TI  - New iron acquisition system in Bacteroidetes.
AB  - Capnocytophaga canimorsus, a dog mouth commensal and a member of the
      Bacteroidetes phylum, causes rare but often fatal septicemia in humans that have
      been in contact with a dog. Here, we show that C. canimorsus strains isolated
      from human infections grow readily in heat-inactivated human serum and that this
      property depends on a typical polysaccharide utilization locus (PUL), namely,
      PUL3 in strain Cc5. PUL are a hallmark of Bacteroidetes, and they encode various
      products, including surface protein complexes that capture and process
      polysaccharides or glycoproteins. The archetype system is the Bacteroides
      thetaiotaomicron Sus system, devoted to starch utilization. Unexpectedly, PUL3
      conferred the capacity to acquire iron from serotransferrin (STF), and this
      capacity required each of the seven encoded proteins, indicating that a whole Sus
      like machinery is acting as an iron capture system (ICS), a new and unexpected
      function for Sus-like machinery. No siderophore could be detected in the culture
      supernatant of C. canimorsus, suggesting that the Sus-like machinery captures
      iron directly from transferrin, but this could not be formally demonstrated. The
      seven genes of the ICS were found in the genomes of several opportunistic
      pathogens from the Capnocytophaga and Prevotella genera, in different isolates of
      the severe poultry pathogen Riemerella anatipestifer, and in strains of
      Bacteroides fragilis and Odoribacter splanchnicus isolated from human infections.
      Thus, this study describes a new type of ICS that evolved in Bacteroidetes from a
      polysaccharide utilization system and most likely represents an important
      virulence factor in this group. 

PMID- 25368115
TI  - Impact of detergent on biophysical properties and immune response of the IpaDB
      fusion protein, a candidate subunit vaccine against Shigella species.
AB  - Shigella spp. are causative agents of bacillary dysentery, a human illness with
      high global morbidity levels, particularly among elderly and infant populations.
      Shigella infects via the fecal-oral route, and its virulence is dependent upon a
      type III secretion system (T3SS). Two components of the exposed needle tip
      complex of the Shigella T3SS, invasion plasmid antigen D (IpaD) and IpaB, have
      been identified as broadly protective antigens in the mouse lethal pneumonia
      model. A recombinant fusion protein (DB fusion) was created by joining the coding
      sequences of IpaD and IpaB. The DB fusion is coexpressed with IpaB's cognate
      chaperone, IpgC, for proper recombinant expression. The chaperone can then be
      removed by using the mild detergents octyl oligooxyethelene (OPOE) or N,N
      dimethyldodecylamine N-oxide (LDAO). The DB fusion in OPOE or LDAO was used for
      biophysical characterization and subsequent construction of an empirical phase
      diagram (EPD). The EPD showed that the DB fusion in OPOE is most stable at
      neutral pH below 55  degrees C. In contrast, the DB fusion in LDAO exhibited
      remarkable thermal plasticity, since this detergent prevents the loss of
      secondary and tertiary structures after thermal unfolding at 90  degrees C, as
      well as preventing thermally induced aggregation. Moreover, the DB fusion in LDAO
      induced higher interleukin-17 secretion and provided a higher protective efficacy
      in a mouse challenge model than did the DB fusion in OPOE. These data indicate
      that LDAO might introduce plasticity to the protein, promoting thermal resilience
      and enhanced protective efficacy, which may be important in its use as a subunit
      vaccine.

PMID- 25368117
TI  - Recombinant ESAT-6-like proteins provoke protective immune responses against
      invasive Staphylococcus aureus disease in a murine model.
AB  - Staphylococcus aureus is a common pathogen found in the community and in
      hospitals. Most notably, methicillin-resistant S. aureus is resistant to many
      antibiotics, which is a growing public health concern. The emergence of drug
      resistant strains has prompted the search for alternative treatments, such as
      immunotherapeutic approaches. To date, most clinical trials of vaccines or of
      passive immunization against S. aureus have ended in failure. In this study, we
      investigated two ESAT-6-like proteins secreted by S. aureus, S. aureus EsxA
      (SaEsxA) and SaEsxB, as possible targets for a vaccine. Mice vaccinated with
      these purified proteins elicited high titers of anti-SaEsxA and anti-SaEsxB
      antibodies, but these antibodies could not prevent S. aureus infection. On the
      other hand, recombinant SaEsxA (rSaEsxA) and rSaEsxB could induce Th1- and Th17
      biased immune responses in mice. Mice immunized with rSaEsxA and rSaEsxB had
      significantly improved survival rates when challenged with S. aureus compared
      with the controls. These findings indicate that SaEsxA and SaEsxB are two
      promising Th1 and Th17 candidate antigens which could be developed into
      multivalent and serotype-independent vaccines against S. aureus infection. 

PMID- 25368116
TI  - Macrophage polarization drives granuloma outcome during Mycobacterium
      tuberculosis infection.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), induces
      formation of granulomas, structures in which immune cells and bacteria
      colocalize. Macrophages are among the most abundant cell types in granulomas and
      have been shown to serve as both critical bactericidal cells and targets for M.
      tuberculosis infection and proliferation throughout the course of infection. Very
      little is known about how these processes are regulated, what controls macrophage
      microenvironment-specific polarization and plasticity, or why some granulomas
      control bacteria and others permit bacterial dissemination. We take a
      computational-biology approach to investigate mechanisms that drive macrophage
      polarization, function, and bacterial control in granulomas. We define a
      "macrophage polarization ratio" as a metric to understand how cytokine signaling
      translates into polarization of single macrophages in a granuloma, which in turn
      modulates cellular functions, including antimicrobial activity and cytokine
      production. Ultimately, we extend this macrophage ratio to the tissue scale and
      define a "granuloma polarization ratio" describing mean polarization measures for
      entire granulomas. Here we coupled experimental data from nonhuman primate TB
      granulomas to our computational model, and we predict two novel and testable
      hypotheses regarding macrophage profiles in TB outcomes. First, the temporal
      dynamics of granuloma polarization ratios are predictive of granuloma outcome.
      Second, stable necrotic granulomas with low CFU counts and limited inflammation
      are characterized by short NF-kappaB signal activation intervals. These results
      suggest that the dynamics of NF-kappaB signaling is a viable therapeutic target
      to promote M1 polarization early during infection and to improve outcome. 

PMID- 25368118
TI  - Sterilizing immunity elicited by Neisseria meningitidis carriage shows broader
      protection than predicted by serum antibody cross-reactivity in CEACAM1-humanized
      mice.
AB  - Neisseria meningitidis asymptomatically colonizes the human upper respiratory
      tract but is also the cause of meningitis and severe septicemia. Carriage or
      disease evokes an immune response against the infecting strain. Hitherto, we have
      known little about the breadth of immunity induced by natural carriage of a
      single strain or its implications for subsequent infectious challenge. In this
      study, we establish that transgenic mice expressing human CEACAM1 support nasal
      colonization by a variety of strains of different capsular types. Next, we
      nasally challenged these mice with either of the N. meningitidis strains H44/76
      (serogroup B, ST-32) and 90/18311 (serogroup C, ST-11), while following the
      induction of strain-specific immunoglobulin. When these antisera were tested for
      reactivity with a diverse panel of N. meningitidis strains, very low levels of
      antibody were detected against all meningococcal strains, yet a mutually
      exclusive "fingerprint" of high-level cross-reactivity toward certain strains
      became apparent. To test the efficacy of these responses for protection against
      subsequent challenge, CEACAM1-humanized mice exposed to strain 90/18311 were then
      rechallenged with different N. meningitidis strains. As expected, the mice were
      immune to challenge with the same strain and with a closely related ST-11 strain,
      38VI, while H44/76 (ST-32) could still colonize these animals. Notably, however,
      despite the paucity of detectable humoral response against strain 196/87 (ST-32),
      this strain was unable to colonize the 90/18311-exposed mice. Combined, our data
      suggest that current approaches may underestimate the actual breadth of mucosal
      protection gained through natural exposure to N. meningitidis strains. 

PMID- 25368119
TI  - Control of acid resistance pathways of enterohemorrhagic Escherichia coli strain
      EDL933 by PsrB, a prophage-encoded AraC-like regulator.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes bloody diarrhea and
      hemolytic-uremic syndrome (HUS) and is the most prevalent E. coli serotype
      associated with food-borne illness worldwide. This pathogen is transmitted via
      the fecal-oral route and has a low infectious dose that has been estimated to be
      between 10 and 100 cells. We and others have previously identified three prophage
      encoded AraC-like transcriptional regulators, PatE, PsrA, and PsrB in the EHEC
      O157:H7 EDL933 strain. Our analysis showed that PatE plays an important role in
      facilitating survival of EHEC under a number of acidic conditions, but the
      contribution of PsrA and PsrB to acid resistance (AR) was unknown. Here, we
      investigated the involvement of PsrA and PsrB in the survival of E. coli O157:H7
      in acid. Our results showed that PsrB, but not PsrA, enhanced the survival of
      strain EDL933 under various acidic conditions. Transcriptional analysis using
      promoter-lacZ reporters and electrophoretic mobility shift assays demonstrated
      that PsrB activates transcription of the hdeA operon, which encodes a major acid
      stress chaperone, by interacting with its promoter region. Furthermore, using a
      mouse model, we showed that expression of PsrB significantly enhanced the ability
      of strain EDL933 to overcome the acidic barrier of the mouse stomach. Taken
      together, our results indicate that EDL933 acquired enhanced acid tolerance via
      horizontally acquired regulatory genes encoding transcriptional regulators that
      activate its AR machinery. 

PMID- 25368120
TI  - Huntingtin is required for ER-to-Golgi transport and for secretory vesicle fusion
      at the plasma membrane.
AB  - Huntingtin is a large membrane-associated scaffolding protein that associates
      with endocytic and exocytic vesicles and modulates their trafficking along
      cytoskeletal tracks. Although the progression of Huntington's disease is linked
      to toxic accumulation of mutant huntingtin protein, loss of wild-type huntingtin
      function might also contribute to neuronal cell death, but its precise function
      is not well understood. Therefore, we investigated the molecular role of
      huntingtin in exocytosis and observed that huntingtin knockdown in HeLa cells
      causes a delay in endoplasmic reticulum (ER)-to-Golgi transport and a reduction
      in the number of cargo vesicles leaving the trans-Golgi network. In addition, we
      found that huntingtin is required for secretory vesicle fusion at the plasma
      membrane. Similar defects in the early exocytic pathway were observed in primary
      fibroblasts from homozygous Htt(140Q/140Q) knock-in mice, which have the
      expansion inserted into the mouse huntingtin gene so lack wild-type huntingtin
      expression. Interestingly, heterozygous fibroblasts from a Huntington's disease
      patient with a 180Q expansion displayed no obvious defects in the early secretory
      pathway. Thus, our results highlight the requirement for wild-type huntingtin at
      distinct steps along the secretory pathway. 

PMID- 25368122
TI  - Multicentric myofibroblastic sarcoma.
AB  - We report a case of synchronous, multicentric low-grade myofibroblastic sarcoma
      presenting in a 62-year-old man. He initially presented with inflammatory
      symmetric polyarthritis and adhesive capsulitis of his shoulder and hips
      bilaterally and did not respond to a trial of disease modifying antirheumatic
      drugs. Over a period of several years he developed progressive restriction of
      both knees and nodules on his hands, both knees and back. A biopsy of the nodule
      on his back was inconclusive and subsequent biopsies on his left and then right
      knee revealed a spindle cell neoplasm with an infiltrative growth pattern,
      mitotic figures, positive immunostaining for smooth muscle actin and focal myxoid
      change consistent with myofibroblastic sarcoma. While myofibroblastic sarcoma has
      been known to metastasise, to our knowledge, a multifocal presentation of this
      tumour has not been described previously. 

PMID- 25368121
TI  - Deficiency of the bone mineralization inhibitor NPP1 protects mice against
      obesity and diabetes.
AB  - The emergence of bone as an endocrine regulator has prompted a re-evaluation of
      the role of bone mineralization factors in the development of metabolic disease.
      Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone
      mineralization through the generation of pyrophosphate, and levels of NPP1 are
      elevated both in dermal fibroblast cultures and muscle of individuals with
      insulin resistance. We investigated the metabolic phenotype associated with
      impaired bone metabolism in mice lacking the gene that encodes NPP1 (Enpp1(-/-)
      mice). Enpp1(-/-) mice exhibited mildly improved glucose homeostasis on a normal
      diet but showed a pronounced resistance to obesity and insulin resistance in
      response to chronic high-fat feeding. Enpp1(-/-) mice had increased levels of the
      insulin-sensitizing bone-derived hormone osteocalcin but unchanged insulin
      signalling within osteoblasts. A fuller understanding of the pathways of NPP1
      could inform the development of novel therapeutic strategies for treating insulin
      resistance. 

PMID- 25368124
TI  - Diffuse large B-cell lymphoma of the cauda equina.
AB  - Primary central nervous system (CNS) lymphoma is a rare form of non-Hodgkin's
      lymphoma. The clinical presentation is variable, depending on its localisation
      within the nervous system. Only 1% of primary CNS lymphoma emerges in the spinal
      cord, and the prevalence of primary lymphoma of the cauda equina is unknown, but
      probably even rarer. Diagnosing primary lymphoma of the cauda equina is
      difficult, since it can mimic other more common disorders such as a herniated
      disc, especially in its early stages. Here we present two cases of primary cauda
      equina lymphoma in which diagnostic work up took a long time, as the final
      diagnosis was only reached after a nerve root biopsy. 

PMID- 25368123
TI  - Primary omental gastrointestinal stromal tumour (GIST) presenting with a large
      abdominal mass and spontaneous haemoperitoneum.
AB  - A 60-year-old Indonesian woman presented with a 9-day history of increasing
      abdominal distension, pain and tiredness. Physical examination revealed
      significant pallor with a palpable mass in the abdomen. CT of the abdomen
      reported a 22 cm complex mass in the peritoneal cavity with free intra-abdominal
      fluid. Laboratory results showed anaemia with a raised serum CA 125 level. At
      laparotomy a large haemorrhagic tumour with blood filled cystic cavities was
      found attached to both greater omentum and the transverse mesocolon with 2.2 L of
      blood in the peritoneal cavity. There was no invasion of any part of the stomach
      or intestines and there were no metastases seen. Histopathology of the resected
      specimen was consistent with that of a gastrointestinal stromal tumour arising
      from the omentum. Immunohistochemical studies revealed the tumour to be strongly
      positive for discovered on GIST-1 (DOG1) but negative for both CD117 and CD34.
      Platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation D842V was
      detected. 

PMID- 25368125
TI  - The hyperdense lumen sign: the tale of the elusive pulmonary embolism.

PMID- 25368126
TI  - Discovering implicit associations in a case of encapsulating peritoneal sclerosis
      complicated by severe mineral imbalance.
AB  - We describe the case of a 42-year-old woman who developed encapsulating
      peritoneal sclerosis (EPS) after 7 years on peritoneal dialysis, with clinical
      relief by enterolysis associated to treatment with tamoxifen, corticosteroids and
      parenteral nutrition in haemodialysis. During the next 7 months, she was also
      conservatively stabilised for mild hyperparathyroidism until she was admitted
      with calciphylaxis, associated with massive extraosseous calcification. Despite
      parathyroidectomy and sodium thiosulfate treatment, which resulted in a
      successful resolution of calciphylaxis, she died 1 year later due to a gross
      calcified peritoneum. In view of controlled hyperparathyroidism, the massive
      extraosseous calcification beginning after EPS diagnosis furthermore corroborates
      a recently suggested role for calcium-regulatory factors associated with poor
      outcome in EPS. 

PMID- 25368127
TI  - An unusual presentation of a retroperitoneal cyst.
AB  - A 34-year-old woman presented to the surgical assessment unit with severe right
      loin to groin pain. An ultrasound scan of the abdomen revealed a complex cyst in
      the right iliac fossa and a subsequent CT scan revealed a 7.5 cm retroperitoneal
      cystic lesion below the lower pole of the right kidney. The patient also had MRI
      of the kidneys, which confirmed the finding. The image showed the cyst was not
      attached to the kidneys and was clearly separate. She underwent a laparoscopic
      excision of the cyst. Histopathology revealed a cyst lined by a single layer of
      mucinous epithelium of endocervical type with foci of calcification and
      hyalinisation on the wall. The cyst was thought to be a benign cyst of Mullerian
      origin. 

PMID- 25368128
TI  - Bilateral acrometastasis in a case renal cell carcinoma.
AB  - We present a unique case of bilateral skeletal metastasis below the knee in a
      patient with renal cell carcinoma. In this rarest of rare cases, bony metastases
      were the first presentation of a primary tumour. Incidentally, the primary tumour
      (renal cell carcinoma) involved the solitary kidney of the patient and the same
      patient also had coexisting carcinoma of the prostate. 

PMID- 25368129
TI  - MRI findings in Tolosa-Hunt syndrome (THS).

PMID- 25368130
TI  - Familial eosinophilic granulomatosis with polyangiitis in a mother and daughter.
AB  - A 17-year-old girl was admitted to our unit with weight loss, dyspnoea,
      arthralgia and sinusitis. Her medical history was noteworthy for bronchial asthma
      and she required systemic steroid therapy. Her mother had a history of
      eosinophilic granulomatosis with polyangiitis (EGPA). Laboratory tests revealed
      excessive eosinophilia and elevated erythrocyte sedimentation. The assay for
      peripheral antineutrophil cytoplasmic antibodies was negative. Histopathological
      examination of lung biopsy revealed EGPA. The patient was treated with
      methylpredinosolone; her eosinophil count normalised and she began to improve
      clinically and radiographically. There is no genetic factor to influence
      susceptibility to this disease. To the best of our knowledge, this is the second
      report of familial EGPA disease in the literature, with a mother and daughter
      both being affected. EGPA disease should be kept in mind in a patient with
      uncontrolled asthma and eosinophilia with a positive family history for EGPA. 

PMID- 25368131
TI  - 'No bladder visible on ultrasound scan--has the patient had a cystectomy?' A case
      of emphysematous cystitis.

PMID- 25368132
TI  - Venous cannula performance assessment in a realistic caval tree model.
AB  - OBJECTIVES: A new caval tree system was designed for realistic in vitro
      simulation. The objective of our study was to assess cannula performance for
      virtually wall-less versus standard percutaneous thin-walled venous cannulas in a
      setting of venous collapse in case of negative pressure. METHODS: For a
      collapsible caval model, a very flexible plastic material was selected, and a
      model with nine afferent veins was designed according to the anatomy of the vena
      cava. A flow bench was built including a lower reservoir holding the caval tree,
      built by taking into account the main afferent vessels and their flow provided by
      a reservoir 6 cm above. A cannula was inserted in this caval tree and connected
      to a centrifugal pump that, in turn, was connected to a reservoir positioned 83
      cm above the second lower reservoir (after-load = 60 mmHg). Using the same pre
      load, the simulated venous drainage for cardiopulmonary bypass was realized using
      a 24 F wall-less cannula (Smartcanula) and 25 F percutaneous cannula
      (Biomedicus), and stepwise increased augmentation (1500 RPM, 2000 and 2500 RPM)
      of venous drainage. RESULTS: For the thin wall and the wall-less cannulas, 36
      pairs of flow and pressure measurements were realized for three different RPM
      values. The mean Q-values at 1500, 2000 and 2500 RPM were: 3.98 +/- 0.01, 6.27 +/
      0.02 and 9.81 +/- 0.02 l/min for the wall-less cannula (P <0.0001), versus 2.74
      +/- 0.02, 3.06 +/- 0.05, 6.78 +/- 0.02 l/min for the thin-wall cannula (P
      <0.0001). The corresponding inlet pressure values were: -8.88 +/- 0.01, -23.69 +/
      0.81 and -70.22 +/- 0.18 mmHg for the wall-less cannula (P <0.0001), versus 
      36.69 +/- 1.88, -80.85 +/- 1.71 and -101.83 +/- 0.45 mmHg for the thin-wall
      cannula (P <0.0001). The thin-wall cannula showed mean Q-values 37% less and mean
      P values 26% more when compared with the wall-less cannula (P <0.0001).
      CONCLUSIONS: Our in vitro water test was able to mimic a negative pressure
      situation, where the wall-less cannula design performs better compared with the
      traditional thin-wall cannula.

PMID- 25368133
TI  - Red blood cell transfusion is a determinant of neurological complications after
      cardiac surgery.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of red blood cell
      (RBC) transfusions on the occurrence of stroke and transient ischaemic attack
      (TIA) after cardiac surgery. METHODS: Data on 14 956 patients undergoing coronary
      artery bypass grafting (CABG) and valve surgery (with or without concomitant
      CABG) were retrieved at three European University Hospitals. The prognostic
      impact of RBC transfusion on postoperative stroke and TIA was investigated by
      logistic regression and multilevel propensity score analysis. RESULTS:
      Postoperative stroke was observed in 147 (1.0%) patients and combined stroke/TIA
      in 238 (1.6%). Of the total population, 6439 (43%) patients received RBC
      transfusion with a median of 2 units (25th-75th percentile, 2-4 units). When
      adjusted for other significant risk factors, RBC transfusion was an independent
      predictor of stroke [odds ratio (OR) 1.14; 95% confidence interval (CI) 1.11-1.17
      per unit] and stroke/TIA (OR 1.12; 95% CI 1.09-1.15 per unit). Increase in the
      amount of transfused RBC units was associated with higher rates of stroke (no RBC
      transfusion: 0.5%, 1-2 RBC units: 1.0%, OR 1.42; >2 RBC units: 2.7%, OR 3.10) and
      stroke/TIA (no RBC transfusion: 0.8%, 1-2 RBC units: 1.8%, OR 1.49; >2 RBC units:
      4.0%, OR 2.72). Multilevel propensity score analysis confirmed these findings and
      showed a very high risk of stroke (3.9%; OR 3.85; 95% CI 2.30-6.45) and
      stroke/TIA (5.9%; OR 3.30; 95% CI 2.17-5.02) associated with transfusion of >=6
      units of RBCs. CONCLUSIONS: Transfusion of more than 2 units of RBCs after
      cardiac surgery is associated with a significantly increased risk of
      postoperative stroke and TIA.

PMID- 25368134
TI  - Presurgical planning using image-based in silico anatomical and functional
      characterization of Tetralogy of Fallot with associated anomalies.
AB  - OBJECTIVES: The ideal vascular reconstruction strategy for anomalies associated
      with Tetralogy of Fallot (ToF) is often driven by observations made at the
      operating table. A method to conduct accurate studies to assess the virtues of a
      certain surgical technique to guide surgical decisions is found wanting. We
      hypothesize that patient-specific computed tomography (CT)-based morphometry
      followed by in silico reconstruction of viable surgical options with haemodynamic
      function assessment using computational fluid dynamics (CFD) can guide surgical
      decisions and help forecast functional outcomes without invasive measurements.
      METHODS: A ToF patient associated with additional left pulmonary artery (LPA)
      stenosis and a patent ductus arteriosus (PDA) who underwent a successful
      correction using a single pericardial patch (SPP) was selected as a reference for
      morphological characterization after 3D anatomical reconstruction from CT images.
      A second patient with morphological similarities established after scaled, co
      registration with the reference patient was selected for virtual correction using
      the same strategy (i.e. SPP repair). CFD was employed for functional analysis of
      pulmonary artery (PA) pressure gradients in the baseline preoperative and
      virtually corrected models, using patient-specific cardiac output and Qp/Qs
      information. RESULTS: SPP repair was modelled in silico following surgical steps
      of PDA ligation, creation of an incision along the LPA and main PA (MPA) and
      finally suturing a rectangular SPP, effectively reducing MPA to LPA angle.
      Analysis of SPP repair revealed significant reduction in right ventricular
      outflow tract-LPA pressure gradient with improved left-right PA flow distribution
      in both patients. CONCLUSIONS: In silico surgery followed by CFD evaluation has
      the potential in augmenting morphology-guided decisions on surgical strategy and
      holds promise in preoperatively determining optimal intervention strategy. This
      is a paradigm-shifting concept to evaluate patient-specific anomalies in a manner
      more objective than mere visual inspection of anatomical traits from radiology
      images. Present studies are focused on an analysis with a larger patient cohort
      to establish a library of ToF patients' successful surgical outcomes to inform
      morphology-based selection of surgical strategy.

PMID- 25368135
TI  - Recurrent acute life-threatening events in a child with achondroplasia.

PMID- 25368136
TI  - Nappy (diaper) rash: what else besides irritant contact dermatitis?
AB  - Nappy (diaper) rash is a common cutaneous disorder of infancy, and diverse
      dermatoses may affect this region. To perform a differential diagnosis can be
      challenging. We present four cases to emphasise the importance of clinical
      diagnosis. 

PMID- 25368137
TI  - Early recognition of occult spinal dysraphism through cutaneous stigmata.

PMID- 25368138
TI  - Pontibacillus salicampi sp. nov., a moderately halophilic bacterium isolated from
      saltern soil.
AB  - A Gram-stain-positive, moderately halophilic bacterium, designated BH043(T), was
      isolated from saltern soil of Gomso in Korea. Cells were motile rods, producing
      ellipsoidal endospores at a terminal position in swollen sporangia. Strain
      BH043(T) was strictly aerobic, grew at pH 6.0-10.0 (optimal growth at pH 7.5), at
      10-55  degrees C (optimal growth at 30  degrees C) and at salinities of 1-20 %
      (w/v) NaCl, growing optimally with 7 % (w/v) NaCl. Phylogenetic analysis based on
      16S rRNA gene sequence indicated that strain BH043(T) belongs to the family
      Bacillaceae and was most closely related to the type strains of the five
      recognized species of the genus Pontibacillus, showing sequence similarity to
      Pontibacillus yanchengensis Y32(T) (97.5 % similarity), Pontibacillus marinus
      BH030004(T) (97.4 %), Pontibacillus chungwhensis BH030062(T) (97.0 %),
      Pontibacillus litoralis JSM 072002(T) (96.4 %) and Pontibacillus halophilus JSM
      076056(T) (96.2 %). The major cellular fatty acids of strain BH043(T) were iso
      C15 : 0 and anteiso-C15 : 0. The genomic DNA G+C content was 42.5 mol%. The major
      isoprenoid quinone was MK-7 and meso-diaminopimelic acid was present in the cell
      wall peptidoglycan as the diagnostic diamino acid. The major polar lipids were
      phosphatidylethanolamine and phosphatidylglycerol. DNA-DNA relatedness between
      strain BH043(T) and the type strains of other species of the genus Pontibacillus,
      P. yanchengensis CGMCC 1.10680(T) and P. marinus KCTC 3917(T) and P. chungwhensis
      KCTC 3890(T), was 35, 24 and 18 %, respectively. On the basis of polyphasic
      analysis from this study, strain BH043(T) represents a novel species of the genus
      Pontibacillus for which the name Pontibacillus salicampi sp. nov. is proposed.
      The type strain is BH043(T) ( = KACC 17607(T) = NBRC 109831(T) = NCAIM
      B.02529(T)).

PMID- 25368139
TI  - Litoribaculum gwangyangense gen. nov., sp. nov., isolated from a sea-tidal flat
      sediment.
AB  - A Gram-stain-negative, strictly aerobic bacterium, designated strain GY12(T), was
      isolated from a tidal flat of South Korea. Cells were moderately halotolerant,
      catalase- and oxidase-positive rods with gliding motility, and were devoid of
      flagella. Growth of strain GY12(T) was observed at 15-40  degrees C (optimum 25
      30  degrees C), pH 6.0-8.5 (optimum pH 7.0-7.5) and with 1-5 % (w/v) NaCl
      (optimum 1-2 %). The major cellular fatty acids were iso-C15 : 1 G, iso-C15 : 0
      and iso-C15 : 0 3-OH. The polar lipids consisted almost entirely of
      phosphatidylethanolamine, two unidentified aminolipids and two unidentified
      lipids. The G+C content of the genomic DNA was 34.8 mol% and the only respiratory
      quinone detected was menaquinone-6 (MK-6). Strain GY12(T) was most closely
      related to the genera Gaetbulibacter, Flaviramulus, Mariniflexile and Tamlana
      with 16S rRNA gene sequence similarities of 94-97 %, but phylogenetic inferences
      based on 16S rRNA gene sequences showed that the strain formed phyletic lineages
      distinct from these genera within the family Flavobacteriaceae. On the basis of
      phenotypic and molecular features, strain GY12(T) represents a novel species of a
      new genus in the family Flavobacteriaceae, for which the name Litoribaculum
      gwangyangense gen. nov., sp. nov. is proposed. The type strain of the type
      species is GY12(T) ( = KACC 16441(T) = JCM 18325(T)).

PMID- 25368140
TI  - Bisgaardia miroungae sp. nov., a new member of the family Pasteurellaceae
      isolated from the oral cavity of northern elephant seals (Mirounga
      angustirostris), and emended description of the genus Bisgaardia.
AB  - A total of 17 bacterial isolates from northern elephant seals, tentatively
      classified within the family Pasteurellaceae, were further characterized by
      genotypic and phenotypic tests. Phylogenetic analysis of partial 16S rRNA and
      rpoB gene sequences showed that the isolates investigated formed a monophyletic
      group, closely related to the genus Bisgaardia within the family Pasteurellaceae.
      The rpoB gene sequence similarity was 97.2-100 % within the group and 16S rRNA
      gene sequence comparisons showed 99.2-99.8 % similarity within the group.
      According to 16S rRNA gene sequence analysis, the most closely related species
      with a validly published name was Bisgaardia hudsonensis with 96.9 % similarity
      and the most closely related species based on rpoB sequence comparison was
      Bisgaardia genomospecies 1 with an rpoB sequence similarity of 90.9 %. All the
      isolates investigated exhibited the phenotypic characteristics of the family
      Pasteurellaceae. However, these isolates could be separated from existing species
      of the genus Bisgaardia by the following characteristics: ability to grow at 42 
      degrees C, and acid production from lactose, melibiose, raffinose and l-rhamnose,
      but not from d-mannitol or trehalose. On the basis of both phylogenetic and
      phenotypic evidence, it is proposed that the strains should be classified as
      representatives of a novel species within the genus Bisgaardia: Bisgaardia
      miroungae sp. nov. The type strain, Wildatric(T) ( = CCUG 65148(T) = DSM
      28141(T)), was isolated from the oral cavity of a wild northern elephant seal at
      The Marine Mammal Center, California, USA in 2011. To include the novel species,
      the description of the genus Bisgaardia has been emended.

PMID- 25368141
TI  - Not surprisingly, no inheritance of a trait results in no evolution.

PMID- 25368142
TI  - Reply to Maxwell et al.: Stable isotopes and their potential for interpreting
      archaeobotanical remains.

PMID- 25368143
TI  - Using multielement isotopic analysis to decipher drought impacts and adaptive
      management in ancient agricultural systems.

PMID- 25368145
TI  - QnAs with Mary C. Waters.

PMID- 25368144
TI  - Negamycin induces translational stalling and miscoding by binding to the small
      subunit head domain of the Escherichia coli ribosome.
AB  - Negamycin is a natural product with broad-spectrum antibacterial activity and
      efficacy in animal models of infection. Although its precise mechanism of action
      has yet to be delineated, negamycin inhibits cellular protein synthesis and
      causes cell death. Here, we show that single point mutations within 16S rRNA that
      confer resistance to negamycin are in close proximity of the tetracycline binding
      site within helix 34 of the small subunit head domain. As expected from its
      direct interaction with this region of the ribosome, negamycin was shown to
      displace tetracycline. However, in contrast to tetracycline-class antibiotics,
      which serve to prevent cognate tRNA from entering the translating ribosome,
      single-molecule fluorescence resonance energy transfer investigations revealed
      that negamycin specifically stabilizes near-cognate ternary complexes within the
      A site during the normally transient initial selection process to promote
      miscoding. The crystal structure of the 70S ribosome in complex with negamycin,
      determined at 3.1 A resolution, sheds light on this finding by showing that
      negamycin occupies a site that partially overlaps that of tetracycline-class
      antibiotics. Collectively, these data suggest that the small subunit head domain
      contributes to the decoding mechanism and that small-molecule binding to this
      domain may either prevent or promote tRNA entry by altering the initial selection
      mechanism after codon recognition and before GTPase activation. 

PMID- 25368146
TI  - Directed evolution of an ultrastable carbonic anhydrase for highly efficient
      carbon capture from flue gas.
AB  - Carbonic anhydrase (CA) is one of nature's fastest enzymes and can dramatically
      improve the economics of carbon capture under demanding environments such as coal
      fired power plants. The use of CA to accelerate carbon capture is limited by the
      enzyme's sensitivity to the harsh process conditions. Using directed evolution,
      the properties of a beta-class CA from Desulfovibrio vulgaris were dramatically
      enhanced. Iterative rounds of library design, library generation, and high
      throughput screening identified highly stable CA variants that tolerate
      temperatures of up to 107  degrees C in the presence of 4.2 M alkaline amine
      solvent at pH >10.0. This increase in thermostability and alkali tolerance
      translates to a 4,000,000-fold improvement over the natural enzyme. At pilot
      scale, the evolved catalyst enhanced the rate of CO2 absorption 25-fold compared
      with the noncatalyzed reaction. 

PMID- 25368148
TI  - Basin-scale estimates of pelagic and coral reef calcification in the Red Sea and
      Western Indian Ocean.
AB  - Basin-scale calcification rates are highly important in assessments of the global
      oceanic carbon cycle. Traditionally, such estimates were based on rates of
      sedimentation measured with sediment traps or in deep sea cores. Here we
      estimated CaCO3 precipitation rates in the surface water of the Red Sea from
      total alkalinity depletion along their axial flow using the water flux in the
      straits of Bab el Mandeb. The relative contribution of coral reefs and open sea
      plankton were calculated by fitting a Rayleigh distillation model to the increase
      in the strontium to calcium ratio. We estimate the net amount of CaCO3
      precipitated in the Red Sea to be 7.3 +/- 0.4.10(10) kg.y(-1) of which 80 +/- 5%
      is by pelagic calcareous plankton and 20 +/- 5% is by the flourishing coastal
      coral reefs. This estimate for pelagic calcification rate is up to 40% higher
      than published sedimentary CaCO3 accumulation rates for the region. The
      calcification rate of the Gulf of Aden was estimated by the Rayleigh model to be
      ~1/2 of the Red Sea, and in the northwestern Indian Ocean, it was smaller than
      our detection limit. The results of this study suggest that variations of major
      ions on a basin scale may potentially help in assessing long-term effects of
      ocean acidification on carbonate deposition by marine organisms. 

PMID- 25368147
TI  - Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud
      cells ex vivo.
AB  - Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its
      homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and
      others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior
      tongue. However, the regenerative potential of Lgr5-expressing (Lgr5(+)) cells
      and the identity of adult taste stem/progenitor cells that regenerate taste
      tissue in anterior tongue remain elusive. In the present work, we describe a
      culture system in which single isolated Lgr5(+) or Lgr6(+) cells from taste
      tissue can generate continuously expanding 3D structures ("organoids"). Many
      cells within these taste organoids were cycling and positive for proliferative
      cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2'-deoxyuridine.
      Importantly, mature taste receptor cells that express gustducin, carbonic
      anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate
      diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids.
      Using calcium imaging assays, we found that cells grown out from taste organoids
      derived from isolated Lgr5(+) cells were functional and responded to tastants in
      a dose-dependent manner. Genetic lineage tracing showed that Lgr6(+) cells gave
      rise to taste bud cells in taste papillae in both anterior and posterior tongue.
      RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste
      stem/progenitor cells both anteriorly and posteriorly. Together, our data
      demonstrate that functional taste cells can be generated ex vivo from single
      Lgr5(+) or Lgr6(+) cells, validating the use of this model for the study of taste
      cell generation. 

PMID- 25368149
TI  - Recent climate and air pollution impacts on Indian agriculture.
AB  - Recent research on the agricultural impacts of climate change has primarily
      focused on the roles of temperature and precipitation. These studies show that
      India has already been negatively affected by recent climate trends. However,
      anthropogenic climate changes are a result of both global emissions of long-lived
      greenhouse gases (LLGHGs) and other short-lived climate pollutants (SLCPs). Two
      potent SLCPs, tropospheric ozone and black carbon, have direct effects on crop
      yields beyond their indirect effects through climate; emissions of black carbon
      and ozone precursors have risen dramatically in India over the past three
      decades. Here, to our knowledge for the first time, we present results of the
      combined effects of climate change and the direct effects of SLCPs on wheat and
      rice yields in India from 1980 to 2010. Our statistical model suggests that,
      averaged over India, yields in 2010 were up to 36% lower for wheat than they
      otherwise would have been, absent climate and pollutant emissions trends, with
      some densely populated states experiencing 50% relative yield losses. [Our point
      estimates for rice (-20%) are similarly large, but not statistically
      significant.] Upper-bound estimates suggest that an overwhelming fraction (90%)
      of these losses is due to the direct effects of SLCPs. Gains from addressing
      regional air pollution could thus counter expected future yield losses resulting
      from direct climate change effects of LLGHGs. 

PMID- 25368150
TI  - Completion of DNA replication in Escherichia coli.
AB  - The mechanism by which cells recognize and complete replicated regions at their
      precise doubling point must be remarkably efficient, occurring thousands of times
      per cell division along the chromosomes of humans. However, this process remains
      poorly understood. Here we show that, in Escherichia coli, the completion of
      replication involves an enzymatic system that effectively counts pairs and limits
      cellular replication to its doubling point by allowing converging replication
      forks to transiently continue through the doubling point before the excess, over
      replicated regions are incised, resected, and joined. Completion requires RecBCD
      and involves several proteins associated with repairing double-strand breaks
      including, ExoI, SbcDC, and RecG. However, unlike double-strand break repair,
      completion occurs independently of homologous recombination and RecA. In some
      bacterial viruses, the completion mechanism is specifically targeted for
      inactivation to allow over-replication to occur during lytic replication. The
      results suggest that a primary cause of genomic instabilities in many double
      strand-break-repair mutants arises from an impaired ability to complete
      replication, independent from DNA damage. 

PMID- 25368152
TI  - Asymmetrical integration of sensory information during mating decisions in
      grasshoppers.
AB  - Decision-making processes, like all traits of an organism, are shaped by
      evolution; they thus carry a signature of the selection pressures associated with
      choice behaviors. The way sexual communication signals are integrated during
      courtship likely reflects the costs and benefits associated with mate choice.
      Here, we study the evaluation of male song by females during acoustic courtship
      in grasshoppers. Using playback experiments and computational modeling we find
      that information of different valence (attractive vs. nonattractive) is weighted
      asymmetrically: while information associated with nonattractive features has
      large weight, attractive features add little to the decision to mate.
      Accordingly, nonattractive features effectively veto female responses. Because
      attractive features have so little weight, the model suggests that female
      responses are frequently driven by integration noise. Asymmetrical weighting of
      negative and positive information may reflect the fitness costs associated with
      mating with a nonattractive over an attractive singer, which are also highly
      asymmetrical. In addition, nonattractive cues tend to be more salient and
      therefore more reliable. Hence, information provided by them should be weighted
      more heavily. Our findings suggest that characterizing the integration of sensory
      information during a natural behavior has the potential to provide valuable
      insights into the selective pressures shaping decision-making during evolution. 

PMID- 25368151
TI  - Stable expression and function of the inositol 1,4,5-triphosphate receptor
      requires palmitoylation by a DHHC6/selenoprotein K complex.
AB  - Calcium (Ca(2+)) is a secondary messenger in cells and Ca(2+) flux initiated from
      endoplasmic reticulum (ER) stores via inositol 1,4,5-triphosphate (IP3) binding
      to the IP3 receptor (IP3R) is particularly important for the activation and
      function of immune cells. Previous studies demonstrated that genetic deletion of
      selenoprotein K (Selk) led to decreased Ca(2+) flux in a variety of immune cells
      and impaired immunity, but the mechanism was unclear. Here we show that Selk
      deficiency does not affect receptor-induced IP3 production, but Selk deficiency
      through genetic deletion or low selenium in culture media leads to low expression
      of the IP3R due to a defect in IP3R palmitoylation. Bioinformatic analysis of the
      DHHC (letters represent the amino acids aspartic acid, histidine, histidine, and
      cysteine in the catalytic domain) family of enzymes that catalyze protein
      palmitoylation revealed that one member, DHHC6, contains a predicted Src-homology
      3 (SH3) domain and DHHC6 is localized to the ER membrane. Because Selk is also an
      ER membrane protein and contains an SH3 binding domain, immunofluorescence and
      coimmunoprecipitation experiments were conducted and revealed DHHC6/Selk
      interactions in the ER membrane that depended on SH3/SH3 binding domain
      interactions. DHHC6 knockdown using shRNA in stably transfected cell lines led to
      decreased expression of the IP3R and impaired IP3R-dependent Ca(2+) flux. Mass
      spectrophotometric and bioinformatic analyses of the IP3R protein identified two
      palmitoylated cysteine residues and another potentially palmitoylated cysteine,
      and mutation of these three cysteines to alanines resulted in decreased IP3R
      palmitoylation and function. These findings reveal IP3R palmitoylation as a
      critical regulator of Ca(2+) flux in immune cells and define a previously
      unidentified DHHC/Selk complex responsible for this process. 

PMID- 25368153
TI  - Differential gradients of interaction affinities drive efficient targeting and
      recycling in the GET pathway.
AB  - Efficient and accurate localization of membrane proteins requires a complex
      cascade of interactions between protein machineries. This requirement is
      exemplified in the guided entry of tail-anchored (TA) protein (GET) pathway,
      where the central targeting factor Get3 must sequentially interact with three
      distinct binding partners to ensure the delivery of TA proteins to the
      endoplasmic reticulum (ER) membrane. To understand the molecular principles that
      provide the vectorial driving force of these interactions, we developed
      quantitative fluorescence assays to monitor Get3-effector interactions at each
      stage of targeting. We show that nucleotide and substrate generate differential
      gradients of interaction energies that drive the ordered interaction of Get3 with
      successive effectors. These data also provide more molecular details on how the
      targeting complex is captured and disassembled by the ER receptor and reveal a
      previously unidentified role for Get4/5 in recycling Get3 from the ER membrane at
      the end of the targeting reaction. These results provide general insights into
      how complex protein interaction cascades are coupled to energy inputs in
      biological systems. 

PMID- 25368154
TI  - Topography's crucial role in Heinrich Events.
AB  - Heinrich Events, the abrupt changes in the Laurentide Ice Sheet that cause the
      appearance of the well-observed Heinrich Layers, are thought to have a strong
      effect on the global climate. The focus of most studies that have looked at the
      climate's response to these events has been the freshwater flux that results from
      melting icebergs. However, there is the possibility that the varying height of
      the ice sheet could force a change in the climate. In this study, we present
      results from a newly developed coupled climate/ice sheet model to show what
      effect this topographic change has both on its own and in concert with the flux
      of freshwater from melting icebergs. We show that the topographic forcing can
      explain a number of the climate changes that are observed during Heinrich Events,
      such as the warming and wettening in Florida and the warm sea surface
      temperatures in the central North Atlantic, which freshwater forcing alone
      cannot. We also find regions, for example the tropical Atlantic, where the
      response is a mixture of the two: Here observations may help disentangle the
      relative importance of each mechanism. These results suggest that the simple
      paradigm of a Heinrich Event causing climate change via freshwater inputs into
      the North Atlantic needs to be revised. 

PMID- 25368155
TI  - BID mediates selective killing of APC-deficient cells in intestinal tumor
      suppression by nonsteroidal antiinflammatory drugs.
AB  - Colorectal tumorigenesis is driven by genetic alterations in the adenomatous
      polyposis coli (APC) tumor suppressor pathway and effectively inhibited by
      nonsteroidal antiinflammatory drugs (NSAIDs). However, how NSAIDs prevent
      colorectal tumorigenesis has remained obscure. We found that the extrinsic
      apoptotic pathway and the BH3 interacting-domain death agonist (BID) are
      activated in adenomas from NSAID-treated patients. Loss of BID abolishes NSAID
      mediated tumor suppression, survival benefit, and apoptosis in tumor-initiating
      stem cells in APC(Min/+) mice. BID-mediated cross-talk between the extrinsic and
      intrinsic apoptotic pathways is responsible for selective killing of neoplastic
      cells by NSAIDs. We further demonstrate that NSAIDs induce death receptor
      signaling in both cancer and normal cells, but only activate BID in cells with
      APC deficiency and ensuing c-Myc activation. Our results suggest that NSAIDs
      suppress intestinal tumorigenesis through BID-mediated synthetic lethality
      triggered by death receptor signaling and gatekeeper mutations, and provide a
      rationale for developing more effective cancer prevention strategies and agents. 

PMID- 25368156
TI  - Late Miocene episodic lakes in the arid Tarim Basin, western China.
AB  - The Tibetan Plateau uplift and Cenozoic global cooling are thought to induce
      enhanced aridification in the Asian interior. Although the onset of Asian
      desertification is proposed to have started in the earliest Miocene, prevailing
      desert environment in the Tarim Basin, currently providing much of the Asian
      eolian dust sources, is only a geologically recent phenomenon. Here we report
      episodic occurrences of lacustrine environments during the Late Miocene and
      investigate how the episodic lakes vanished in the basin. Our oxygen isotopic
      (delta(18)O) record demonstrates that before the prevailing desert environment,
      episodic changes frequently alternating between lacustrine and fluvial-eolian
      environments can be linked to orbital variations. Wetter lacustrine phases
      generally corresponded to periods of high eccentricity and possibly high
      obliquity, and vice versa, suggesting a temperature control on the regional
      moisture level on orbital timescales. Boron isotopic (delta(11)B) and delta(18)O
      records, together with other geochemical indicators, consistently show that the
      episodic lakes finally dried up at ~4.9 million years ago (Ma), permanently and
      irreversibly. Although the episodic occurrences of lakes appear to be linked to
      orbitally induced global climatic changes, the plateau (Tibetan, Pamir, and
      Tianshan) uplift was primarily responsible for the final vanishing of the
      episodic lakes in the Tarim Basin, occurring at a relatively warm, stable climate
      period. 

PMID- 25368157
TI  - Rapid changes in the gut microbiome during human evolution.
AB  - Humans are ecosystems containing trillions of microorganisms, but the
      evolutionary history of this microbiome is obscured by a lack of knowledge about
      microbiomes of African apes. We sequenced the gut communities of hundreds of
      chimpanzees, bonobos, and gorillas and developed a phylogenetic approach to
      reconstruct how present-day human microbiomes have diverged from those of
      ancestral populations. Compositional change in the microbiome was slow and clock
      like during African ape diversification, but human microbiomes have deviated from
      the ancestral state at an accelerated rate. Relative to the microbiomes of wild
      apes, human microbiomes have lost ancestral microbial diversity while becoming
      specialized for animal-based diets. Individual wild apes cultivate more phyla,
      classes, orders, families, genera, and species of bacteria than do individual
      humans across a range of societies. These results indicate that humanity has
      experienced a depletion of the gut flora since diverging from Pan. 

PMID- 25368159
TI  - The MuSK activator agrin has a separate role essential for postnatal maintenance
      of neuromuscular synapses.
AB  - The motoneural control of skeletal muscle contraction requires the neuromuscular
      junction (NMJ), a midmuscle synapse between the motor nerve and myotube. The
      formation and maintenance of NMJs are orchestrated by the muscle-specific
      receptor tyrosine kinase (MuSK). Motor neuron-derived agrin activates MuSK via
      binding to MuSK's coreceptor Lrp4, and genetic defects in agrin underlie a
      congenital myasthenic syndrome (an NMJ disorder). However, MuSK-dependent
      postsynaptic differentiation of NMJs occurs in the absence of a motor neuron,
      indicating a need for nerve/agrin-independent MuSK activation. We previously
      identified the muscle protein Dok-7 as an essential activator of MuSK. Although
      NMJ formation requires agrin under physiological conditions, it is dispensable
      for NMJ formation experimentally in the absence of the neurotransmitter
      acetylcholine, which inhibits postsynaptic specialization. Thus, it was
      hypothesized that MuSK needs agrin together with Lrp4 and Dok-7 to achieve
      sufficient activation to surmount inhibition by acetylcholine. Here, we show that
      forced expression of Dok-7 in muscle enhanced MuSK activation in mice lacking
      agrin or Lrp4 and restored midmuscle NMJ formation in agrin-deficient mice, but
      not in Lrp4-deficient mice, probably due to the loss of Lrp4-dependent
      presynaptic differentiation. However, these NMJs in agrin-deficient mice rapidly
      disappeared after birth, and postsynaptic specializations emerged ectopically
      throughout myotubes whereas exogenous Dok-7-mediated MuSK activation was
      maintained. These findings demonstrate that the MuSK activator agrin plays
      another role essential for the postnatal maintenance, but not for embryonic
      formation, of NMJs and also for the postnatal, but not prenatal, midmuscle
      localization of postsynaptic specializations, providing physiological and
      pathophysiological insight into NMJ homeostasis. 

PMID- 25368158
TI  - Calcium-mediated histone modifications regulate alternative splicing in
      cardiomyocytes.
AB  - In cardiomyocytes, calcium is known to control gene expression at the level of
      transcription, whereas its role in regulating alternative splicing has not been
      explored. Here we report that, in mouse primary or embryonic stem cell-derived
      cardiomyocytes, increased calcium levels induce robust and reversible skipping of
      several alternative exons from endogenously expressed genes. Interestingly, we
      demonstrate a calcium-mediated splicing regulatory mechanism that depends on
      changes of histone modifications. Specifically, the regulation occurs through
      changes in calcium-responsive kinase activities that lead to alterations in
      histone modifications and subsequent changes in the transcriptional elongation
      rate and exon skipping. We demonstrate that increased intracellular calcium
      levels lead to histone hyperacetylation along the body of the genes containing
      calcium-responsive alternative exons by disrupting the histone deacetylase-to
      histone acetyltransferase balance in the nucleus. Consequently, the RNA
      polymerase II elongation rate increases significantly on those genes, resulting
      in skipping of the alternative exons. These studies reveal a mechanism by which
      calcium-level changes in cardiomyocytes impact on the output of gene expression
      through altering alternative pre-mRNA splicing patterns. 

PMID- 25368160
TI  - Probabilistic cognition in two indigenous Mayan groups.
AB  - Is there a sense of chance shared by all individuals, regardless of their
      schooling or culture? To test whether the ability to make correct probabilistic
      evaluations depends on educational and cultural guidance, we investigated
      probabilistic cognition in preliterate and prenumerate Kaqchikel and K'iche', two
      indigenous Mayan groups, living in remote areas of Guatemala. Although the tested
      individuals had no formal education, they performed correctly in tasks in which
      they had to consider prior and posterior information, proportions and
      combinations of possibilities. Their performance was indistinguishable from that
      of Mayan school children and Western controls. Our results provide evidence for
      the universal nature of probabilistic cognition. 

PMID- 25368163
TI  - Overtone-based pitch selection in hermit thrush song: unexpected convergence with
      scale construction in human music.
AB  - Many human musical scales, including the diatonic major scale prevalent in
      Western music, are built partially or entirely from intervals (ratios between
      adjacent frequencies) corresponding to small-integer proportions drawn from the
      harmonic series. Scientists have long debated the extent to which principles of
      scale generation in human music are biologically or culturally determined. Data
      from animal "song" may provide new insights into this discussion. Here, by
      examining pitch relationships using both a simple linear regression model and a
      Bayesian generative model, we show that most songs of the hermit thrush (Catharus
      guttatus) favor simple frequency ratios derived from the harmonic (or overtone)
      series. Furthermore, we show that this frequency selection results not from
      physical constraints governing peripheral production mechanisms but from active
      selection at a central level. These data provide the most rigorous empirical
      evidence to date of a bird song that makes use of the same mathematical
      principles that underlie Western and many non-Western musical scales,
      demonstrating surprising convergence between human and animal "song cultures."
      Although there is no evidence that the songs of most bird species follow the
      overtone series, our findings add to a small but growing body of research showing
      that a preference for small-integer frequency ratios is not unique to humans.
      These findings thus have important implications for current debates about the
      origins of human musical systems and may call for a reevaluation of existing
      theories of musical consonance based on specific human vocal characteristics. 

PMID- 25368162
TI  - EGR2 is critical for peripheral naive T-cell differentiation and the T-cell
      response to influenza.
AB  - Early growth response 2 (EGR2) transcription factor negatively regulates T-cell
      activation, in contrast to the positive regulation of this process by EGR1. Here,
      we unexpectedly found that EGR2 promotes peripheral naive T-cell differentiation,
      with delayed T-cell receptor-induced proliferation in naive T cells from Egr2
      conditional knockout (CKO) mice and decreased production of IFN-gamma, IL-4, IL
      9, and IL-17A in cells subjected to T-helper differentiation. Moreover, genes
      that promote T-cell activation, including Tbx21 and Notch1, had decreased
      expression in Egr2 CKO T cells and are direct EGR2 target genes. Following
      influenza infection, Egr2 CKO mice had delayed viral clearance, more weight loss,
      and more severe pathological changes in the lung than did WT and Egr1 KO mice,
      with decreased production of effector cytokines, increased infiltration of
      antigen-specific memory-precursor CD8(+) T cells, and lower numbers of lung
      resident memory CD8(+) T cells. Thus, unexpectedly, EGR2 can function as a
      positive regulator that is essential for naive T-cell differentiation and in vivo
      T-cell responses to a viral infection. 

PMID- 25368161
TI  - Trajectory and genomic determinants of fungal-pathogen speciation and host
      adaptation.
AB  - Much remains unknown regarding speciation. Host-pathogen interactions are a major
      driving force for diversification, but the genomic basis for speciation and host
      shifting remains unclear. The fungal genus Metarhizium contains species ranging
      from specialists with very narrow host ranges to generalists that attack a wide
      range of insects. By genomic analyses of seven species, we demonstrated that
      generalists evolved from specialists via transitional species with intermediate
      host ranges and that this shift paralleled insect evolution. We found that
      specialization was associated with retention of sexuality and rapid evolution of
      existing protein sequences whereas generalization was associated with protein
      family expansion, loss of genome-defense mechanisms, genome restructuring,
      horizontal gene transfer, and positive selection that accelerated after
      reinforcement of reproductive isolation. These results advance understanding of
      speciation and genomic signatures that underlie pathogen adaptation to hosts. 

PMID- 25368164
TI  - c-Abl tyrosine kinase promotes adipocyte differentiation by targeting PPAR-gamma
      2.
AB  - Adipocyte differentiation, or adipogenesis, is a complex and highly regulated
      process. A recent proteomic analysis has predicted that the nonreceptor tyrosine
      kinase Abelson murine leukemia viral oncogene (c-Abl) is a putative key regulator
      of adipogenesis, but the underlying mechanism remained obscure. We found that c
      Abl was activated during the early phase of mouse 3T3-L1 preadipocyte
      differentiation. Moreover, c-Abl activity was essential and its inhibition
      blocked differentiation to mature adipocytes. c-Abl directly controlled the
      expression and activity of the master adipogenic regulator peroxisome
      proliferator-activator receptor gamma 2 (PPARgamma2). PPARgamma2 physically
      associated with c-Abl and underwent phosphorylation on two tyrosine residues
      within its regulatory activation function 1 (AF1) domain. We demonstrated that
      this process positively regulates PPARgamma2 stability and adipogenesis.
      Remarkably, c-Abl binding to PPARgamma2 required the Pro12 residue that has a
      phenotypically well-studied common human genetic proline 12 alanine substitution
      (Pro12Ala) polymorphism. Our findings establish a critical role for c-Abl in
      adipocyte differentiation and explain the behavior of the known Pro12Ala
      polymorphism. 

PMID- 25368165
TI  - Purpose in life and use of preventive health care services.
AB  - Purpose in life has been linked with better health (mental and physical) and
      health behaviors, but its link with patterns of health care use are understudied.
      We hypothesized that people with higher purpose would be more proactive in taking
      care of their health, as indicated by a higher likelihood of using preventive
      health care services. We also hypothesized that people with higher purpose would
      spend fewer nights in the hospital. Participants (n = 7,168) were drawn from the
      Health and Retirement Study, a nationally representative panel study of American
      adults over the age of 50, and tracked for 6 y. After adjusting for
      sociodemographic factors, each unit increase in purpose (on a six-point scale)
      was associated with a higher likelihood that people would obtain a cholesterol
      test [odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08-1.29] or
      colonoscopy (OR = 1.06, 95% CI = 0.99-1.14). Furthermore, females were more
      likely to receive a mammogram/X-ray (OR = 1.27, 95% CI = 1.16-1.39) or pap smear
      (OR = 1.16, 95% CI = 1.06-1.28), and males were more likely to receive a prostate
      examination (OR = 1.31, 95% CI = 1.18-1.45). Each unit increase in purpose was
      also associated with 17% fewer nights spent in the hospital (rate ratio = 0.83,
      95% CI = 0.77-0.89). An increasing number of randomized controlled trials show
      that purpose in life can be raised. Therefore, with additional research, findings
      from this study may inform the development of new strategies that increase the
      use of preventive health care services, offset the burden of rising health care
      costs, and enhance the quality of life among people moving into the ranks of our
      aging society. 

PMID- 25368166
TI  - Decreased polycystin 2 expression alters calcium-contraction coupling and changes
      beta-adrenergic signaling pathways.
AB  - Cardiac disorders are the main cause of mortality in autosomal-dominant
      polycystic kidney disease (ADPKD). However, how mutated polycystins predispose
      patients with ADPKD to cardiac pathologies before development of renal
      dysfunction is unknown. We investigate the effect of decreased levels of
      polycystin 2 (PC2), a calcium channel that interacts with the ryanodine receptor,
      on myocardial function. We hypothesize that heterozygous PC2 mice (Pkd2(+/-))
      undergo cardiac remodeling as a result of changes in calcium handling, separate
      from renal complications. We found that Pkd2(+/-) cardiomyocytes have altered
      calcium handling, independent of desensitized calcium-contraction coupling.
      Paradoxically, in Pkd2(+/-) mice, protein kinase A (PKA) phosphorylation of
      phospholamban (PLB) was decreased, whereas PKA phosphorylation of troponin I was
      increased, explaining the decoupling between calcium signaling and contractility.
      In silico modeling supported this relationship. Echocardiography measurements
      showed that Pkd2(+/-) mice have increased left ventricular ejection fraction
      after stimulation with isoproterenol (ISO), a beta-adrenergic receptor (betaAR)
      agonist. Blockers of betaAR-1 and betaAR-2 inhibited the ISO response in Pkd2(+/
      ) mice, suggesting that the dephosphorylated state of PLB is primarily by betaAR
      2 signaling. Importantly, the Pkd2(+/-) mice were normotensive and had no
      evidence of renal cysts. Our results showed that decreased PC2 levels shifted the
      betaAR pathway balance and changed expression of calcium handling proteins, which
      resulted in altered cardiac contractility. We propose that PC2 levels in the
      heart may directly contribute to cardiac remodeling in patients with ADPKD in the
      absence of renal dysfunction. 

PMID- 25368167
TI  - Nep1-like proteins from three kingdoms of life act as a microbe-associated
      molecular pattern in Arabidopsis.
AB  - Necrosis and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) are secreted
      by a wide range of plant-associated microorganisms. They are best known for their
      cytotoxicity in dicot plants that leads to the induction of rapid tissue necrosis
      and plant immune responses. The biotrophic downy mildew pathogen Hyaloperonospora
      arabidopsidis encodes 10 different noncytotoxic NLPs (HaNLPs) that do not cause
      necrosis. We discovered that these noncytotoxic NLPs, however, act as potent
      activators of the plant immune system in Arabidopsis thaliana. Ectopic expression
      of HaNLP3 in Arabidopsis triggered resistance to H. arabidopsidis, activated the
      expression of a large set of defense-related genes, and caused a reduction of
      plant growth that is typically associated with strongly enhanced immunity. N- and
      C-terminal deletions of HaNLP3, as well as amino acid substitutions, pinpointed
      to a small central region of the protein that is required to trigger immunity,
      indicating the protein acts as a microbe-associated molecular pattern (MAMP).
      This was confirmed in experiments with a synthetic peptide of 24 aa, derived from
      the central part of HaNLP3 and corresponding to a conserved region in type 1 NLPs
      that induces ethylene production, a well-known MAMP response. Strikingly,
      corresponding 24-aa peptides of fungal and bacterial type 1 NLPs were also able
      to trigger immunity in Arabidopsis. The widespread phylogenetic distribution of
      type 1 NLPs makes this protein family (to our knowledge) the first proteinaceous
      MAMP identified in three different kingdoms of life. 

PMID- 25368168
TI  - Isotopically nonstationary 13C flux analysis of changes in Arabidopsis thaliana
      leaf metabolism due to high light acclimation.
AB  - Improving plant productivity is an important aim for metabolic engineering. There
      are few comprehensive methods that quantitatively describe leaf metabolism,
      although such information would be valuable for increasing photosynthetic
      capacity, enhancing biomass production, and rerouting carbon flux toward
      desirable end products. Isotopically nonstationary metabolic flux analysis (INST
      MFA) has been previously applied to map carbon fluxes in photoautotrophic
      bacteria, which involves model-based regression of transient (13)C-labeling
      patterns of intracellular metabolites. However, experimental and computational
      difficulties have hindered its application to terrestrial plant systems. We
      performed in vivo isotopic labeling of Arabidopsis thaliana rosettes with (13)CO2
      and estimated fluxes throughout leaf photosynthetic metabolism by INST-MFA.
      Plants grown at 200 umol m(-2)s(-1) light were compared with plants acclimated
      for 9 d at an irradiance of 500 umol?m(-2)?s(-1). Approximately 1,400 independent
      mass isotopomer measurements obtained from analysis of 37 metabolite fragment
      ions were regressed to estimate 136 total fluxes (54 free fluxes) under each
      condition. The results provide a comprehensive description of changes in carbon
      partitioning and overall photosynthetic flux after long-term developmental
      acclimation of leaves to high light. Despite a doubling in the carboxylation
      rate, the photorespiratory flux increased from 17 to 28% of net CO2 assimilation
      with high-light acclimation (Vc/Vo: 3.5:1 vs. 2.3:1, respectively). This study
      highlights the potential of (13)C INST-MFA to describe emergent flux phenotypes
      that respond to environmental conditions or plant physiology and cannot be
      obtained by other complementary approaches. 

PMID- 25368169
TI  - Closing the sea level budget at the Last Glacial Maximum.

PMID- 25368170
TI  - Ventromedial prefrontal cortex supports affective future simulation by
      integrating distributed knowledge.
AB  - Although the future often seems intangible, we can make it more concrete by
      imagining prospective events. Here, using functional MRI, we demonstrate a
      mechanism by which the ventromedial prefrontal cortex supports such episodic
      simulations, and thereby contributes to affective foresight: This region supports
      processes that (i) integrate knowledge related to the elements that constitute an
      episode and (ii) represent the episode's emergent affective quality. The
      ventromedial prefrontal cortex achieves such integration via interactions with
      distributed cortical regions that process the individual elements. Its activation
      then signals the affective quality of the ensuing episode, which goes beyond the
      combined affective quality of its constituting elements. The integrative process
      further augments long-term retention of the episode, making it available at later
      time points. This mechanism thus renders the future tangible, providing a basis
      for farsighted behavior. 

PMID- 25368171
TI  - Sexual transfer of the steroid hormone 20E induces the postmating switch in
      Anopheles gambiae.
AB  - Female insects generally mate multiple times during their lives. A notable
      exception is the female malaria mosquito Anopheles gambiae, which after sex loses
      her susceptibility to further copulation. Sex in this species also renders
      females competent to lay eggs developed after blood feeding. Despite intense
      research efforts, the identity of the molecular triggers that cause the
      postmating switch in females, inducing a permanent refractoriness to further
      mating and triggering egg-laying, remains elusive. Here we show that the male
      transferred steroid hormone 20-hydroxyecdysone (20E) is a key regulator of
      monandry and oviposition in An. gambiae. When sexual transfer of 20E is impaired
      by partial inactivation of the hormone and inhibition of its biosynthesis in
      males, oviposition and refractoriness to further mating in the female are
      strongly reduced. Conversely, mimicking sexual delivery by injecting 20E into
      virgin females switches them to an artificial mated status, triggering egg-laying
      and reducing susceptibility to copulation. Sexual transfer of 20E appears to
      incapacitate females physically from receiving seminal fluids by a second male.
      Comparative analysis of microarray data from females after mating and after 20E
      treatment indicates that 20E-regulated molecular pathways likely are implicated
      in the postmating switch, including cytoskeleton and musculature-associated genes
      that may render the atrium impenetrable to additional mates. By revealing signals
      and pathways shaping key processes in the An. gambiae reproductive biology, our
      data offer new opportunities for the control of natural populations of malaria
      vectors. 

PMID- 25368172
TI  - Deciding whether follow-up studies have replicated findings in a preliminary
      large-scale omics study.
AB  - We propose a formal method to declare that findings from a primary study have
      been replicated in a follow-up study. Our proposal is appropriate for primary
      studies that involve large-scale searches for rare true positives (i.e., needles
      in a haystack). Our proposal assigns an r value to each finding; this is the
      lowest false discovery rate at which the finding can be called replicated.
      Examples are given and software is available. 

PMID- 25368173
TI  - Maximum likelihood inference of reticulate evolutionary histories.
AB  - Hybridization plays an important role in the evolution of certain groups of
      organisms, adaptation to their environments, and diversification of their
      genomes. The evolutionary histories of such groups are reticulate, and methods
      for reconstructing them are still in their infancy and have limited
      applicability. We present a maximum likelihood method for inferring reticulate
      evolutionary histories while accounting simultaneously for incomplete lineage
      sorting. Additionally, we propose methods for assessing confidence in the amount
      of reticulation and the topology of the inferred evolutionary history. Our method
      obtains accurate estimates of reticulate evolutionary histories on simulated
      datasets. Furthermore, our method provides support for a hypothesis of a
      reticulate evolutionary history inferred from a set of house mouse (Mus musculus)
      genomes. As evidence of hybridization in eukaryotic groups accumulates, it is
      essential to have methods that infer reticulate evolutionary histories. The work
      we present here allows for such inference and provides a significant step toward
      putting phylogenetic networks on par with phylogenetic trees as a model of
      capturing evolutionary relationships. 

PMID- 25368174
TI  - Excess cholesterol induces mouse egg activation and may cause female infertility.
AB  - The HDL receptor scavenger receptor, class B type I (SR-BI) controls the
      structure and fate of plasma HDL. Female SR-BI KO mice are infertile, apparently
      because of their abnormal cholesterol-enriched HDL particles. We examined the
      growth and meiotic progression of SR-BI KO oocytes and found that they underwent
      normal germinal vesicle breakdown; however, SR-BI KO eggs, which had accumulated
      excess cholesterol in vivo, spontaneously activated, and they escaped metaphase
      II (MII) arrest and progressed to pronuclear, MIII, and anaphase/telophase III
      stages. Eggs from fertile WT mice were activated when loaded in vitro with excess
      cholesterol by a cholesterol/methyl-beta-cyclodextrin complex, phenocopying SR-BI
      KO oocytes. In vitro cholesterol loading of eggs induced reduction in maturation
      promoting factor and MAPK activities, elevation of intracellular calcium,
      extrusion of a second polar body, and progression to meiotic stages beyond MII.
      These results suggest that the infertility of SR-BI KO females is caused, at
      least in part, by excess cholesterol in eggs inducing premature activation and
      that cholesterol can activate WT mouse eggs to escape from MII arrest. Analysis
      of SR-BI KO female infertility raises the possibility that abnormalities in
      cholesterol metabolism might underlie some cases of human female infertility of
      unknown etiology. 

PMID- 25368175
TI  - New pasture plants intensify invasive species risk.
AB  - Agricultural intensification is critical to meet global food demand, but
      intensification threatens native species and degrades ecosystems. Sustainable
      intensification (SI) is heralded as a new approach for enabling growth in
      agriculture while minimizing environmental impacts. However, the SI literature
      has overlooked a major environmental risk. Using data from eight countries on six
      continents, we show that few governments regulate conventionally bred pasture
      taxa to limit threats to natural areas, even though most agribusinesses promote
      taxa with substantial weed risk. New pasture taxa (including species, subspecies,
      varieties, cultivars, and plant-endophyte combinations) are bred with
      characteristics typical of invasive species and environmental weeds. By
      introducing novel genetic and endophyte variation, pasture taxa are imbued with
      additional capacity for invasion and environmental impact. New strategies to
      prevent future problems are urgently needed. We highlight opportunities for
      researchers, agribusiness, and consumers to reduce environmental risks associated
      with new pasture taxa. We also emphasize four main approaches that governments
      could consider as they build new policies to limit weed risks, including (i)
      national lists of taxa that are prohibited based on environmental risk; (ii) a
      weed risk assessment for all new taxa; (iii) a program to rapidly detect and
      control new taxa that invade natural areas; and (iv) the polluter-pays principle,
      so that if a taxon becomes an environmental weed, industry pays for its
      management. There is mounting pressure to increase livestock production. With
      foresight and planning, growth in agriculture can be achieved sustainably
      provided that the scope of SI expands to encompass environmental weed risks. 

PMID- 25368176
TI  - Simple battery armor to protect against gastrointestinal injury from accidental
      ingestion.
AB  - Inadvertent battery ingestion in children and the associated morbidity and
      mortality results in thousands of emergency room visits every year. Given the
      risk for serious electrochemical burns within hours of ingestion, the current
      standard of care for the treatment of batteries in the esophagus is emergent
      endoscopic removal. Safety standards now regulate locked battery compartments in
      toys, which have resulted in a modest reduction in inadvertent battery ingestion;
      specifically, 3,461 ingestions were reported in 2009, and 3,366 in 2013. Aside
      from legislation, minimal technological development has taken place at the level
      of the battery to limit injury. We have constructed a waterproof, pressure
      sensitive coating, harnessing a commercially available quantum tunneling
      composite. Quantum tunneling composite coated (QTCC) batteries are nonconductive
      in the low-pressure gastrointestinal environment yet conduct within the higher
      pressure of standard battery housings. Importantly, this coating technology
      enables most battery-operated equipment to be powered without modification. If
      these new batteries are swallowed, they limit the external electrolytic currents
      responsible for tissue injury. We demonstrate in a large-animal model a
      significant decrease in tissue injury with QTCC batteries compared with uncoated
      control batteries. In summary, here we describe a facile approach to increasing
      the safety of batteries by minimizing the risk for electrochemical burn if the
      batteries are inadvertently ingested, without the need for modification of most
      battery-powered devices. 

PMID- 25368177
TI  - Cannabinoid CB2 receptors modulate midbrain dopamine neuronal activity and
      dopamine-related behavior in mice.
AB  - Cannabinoid CB2 receptors (CB2Rs) have been recently reported to modulate brain
      dopamine (DA)-related behaviors; however, the cellular mechanisms underlying
      these actions are unclear. Here we report that CB2Rs are expressed in ventral
      tegmental area (VTA) DA neurons and functionally modulate DA neuronal
      excitability and DA-related behavior. In situ hybridization and
      immunohistochemical assays detected CB2 mRNA and CB2R immunostaining in VTA DA
      neurons. Electrophysiological studies demonstrated that activation of CB2Rs by
      JWH133 or other CB2R agonists inhibited VTA DA neuronal firing in vivo and ex
      vivo, whereas microinjections of JWH133 into the VTA inhibited cocaine self
      administration. Importantly, all of the above findings observed in WT or CB1(-/-)
      mice are blocked by CB2R antagonist and absent in CB2(-/-) mice. These data
      suggest that CB2R-mediated reduction of VTA DA neuronal activity may underlie
      JWH133's modulation of DA-regulated behaviors.

PMID- 25368178
TI  - Asymmetric hindwing foldings in rove beetles.
AB  - Foldable wings of insects are the ultimate deployable structures and have
      attracted the interest of aerospace engineering scientists as well as
      entomologists. Rove beetles are known to fold their wings in the most
      sophisticated ways that have right-left asymmetric patterns. However, the
      specific folding process and the reason for this asymmetry remain unclear. This
      study reveals how these asymmetric patterns emerge as a result of the folding
      process of rove beetles. A high-speed camera was used to reveal the details of
      the wing-folding movement. The results show that these characteristic
      asymmetrical patterns emerge as a result of simultaneous folding of overlapped
      wings. The revealed folding mechanisms can achieve not only highly compact wing
      storage but also immediate deployment. In addition, the right and left crease
      patterns are interchangeable, and thus each wing internalizes two crease patterns
      and can be folded in two different ways. This two-way folding gives freedom of
      choice for the folding direction to a rove beetle. The use of asymmetric patterns
      and the capability of two-way folding are unique features not found in artificial
      structures. These features have great potential to extend the design
      possibilities for all deployable structures, from space structures to articles of
      daily use. 

PMID- 25368179
TI  - Anatomical accuracy of brain connections derived from diffusion MRI tractography
      is inherently limited.
AB  - Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the
      structural connections of the human brain. Its accuracy is known to be limited by
      technical factors affecting in vivo data acquisition, such as noise, artifacts,
      and data undersampling resulting from scan time constraints. It generally is
      assumed that improvements in data quality and implementation of sophisticated
      tractography methods will lead to increasingly accurate maps of human anatomical
      connections. However, assessing the anatomical accuracy of DWI tractography is
      difficult because of the lack of independent knowledge of the true anatomical
      connections in humans. Here we investigate the future prospects of DWI-based
      connectional imaging by applying advanced tractography methods to an ex vivo DWI
      dataset of the macaque brain. The results of different tractography methods were
      compared with maps of known axonal projections from previous tracer studies in
      the macaque. Despite the exceptional quality of the DWI data, none of the methods
      demonstrated high anatomical accuracy. The methods that showed the highest
      sensitivity showed the lowest specificity, and vice versa. Additionally,
      anatomical accuracy was highly dependent upon parameters of the tractography
      algorithm, with different optimal values for mapping different pathways. These
      results suggest that there is an inherent limitation in determining long-range
      anatomical projections based on voxel-averaged estimates of local fiber
      orientation obtained from DWI data that is unlikely to be overcome by
      improvements in data acquisition and analysis alone. 

PMID- 25368180
TI  - Notes on the role of dynamic DNA methylation in mammalian development.
AB  - It has been nearly 40 y since it was suggested that genomic methylation patterns
      could be transmitted via maintenance methylation during S phase and might play a
      role in the dynamic regulation of gene expression during development [Holliday R,
      Pugh JE (1975) Science 187(4173):226-232; Riggs AD (1975) Cytogenet Cell Genet
      14(1):9-25]. This revolutionary proposal was justified by "... our almost
      complete ignorance of the mechanism for the unfolding of the genetic program
      during development" that prevailed at the time. Many correlations between
      transcriptional activation and demethylation have since been reported, but
      causation has not been demonstrated and to date there is no reasonable proof of
      the existence of a complex biochemical system that activates and represses genes
      via reversible DNA methylation. Such a system would supplement or replace the
      conserved web of transcription factors that regulate cellular differentiation in
      organisms that have unmethylated genomes (such as Caenorhaditis elegans and the
      Dipteran insects) and those that methylate their genomes. DNA methylation does
      have essential roles in irreversible promoter silencing, as in the monoallelic
      expression of imprinted genes, in the silencing of transposons, and in X
      chromosome inactivation in female mammals. Rather than reinforcing or replacing
      regulatory pathways that are conserved between organisms that have either
      methylated or unmethylated genomes, DNA methylation endows genomes with the
      ability to subject specific sequences to irreversible transcriptional silencing
      even in the presence of all of the factors required for their expression, an
      ability that is generally unavailable to organisms that have unmethylated
      genomes. 

PMID- 25368181
TI  - Basal and beta-adrenergic regulation of the cardiac calcium channel CaV1.2
      requires phosphorylation of serine 1700.
AB  - L-type calcium (Ca(2+)) currents conducted by voltage-gated Ca(2+) channel CaV1.2
      initiate excitation-contraction coupling in cardiomyocytes. Upon activation of
      beta-adrenergic receptors, phosphorylation of CaV1.2 channels by cAMP-dependent
      protein kinase (PKA) increases channel activity, thereby allowing more Ca(2+)
      entry into the cell, which leads to more forceful contraction. In vitro
      reconstitution studies and in vivo proteomics analysis have revealed that Ser
      1700 is a key site of phosphorylation mediating this effect, but the functional
      role of this amino acid residue in regulation in vivo has remained uncertain.
      Here we have studied the regulation of calcium current and cell contraction of
      cardiomyocytes in vitro and cardiac function and homeostasis in vivo in a mouse
      line expressing the mutation Ser-1700-Ala in the CaV1.2 channel. We found that
      preventing phosphorylation at this site decreased the basal L-type CaV1.2 current
      in both neonatal and adult cardiomyocytes. In addition, the incremental increase
      elicited by isoproterenol was abolished in neonatal cardiomyocytes and was
      substantially reduced in young adult myocytes. In contrast, cellular
      contractility was only moderately reduced compared with wild type, suggesting a
      greater reserve of contractile function and/or recruitment of compensatory
      mechanisms. Mutant mice develop cardiac hypertrophy by the age of 3-4 mo, and
      maximal stress-induced exercise tolerance is reduced, indicating impaired
      physiological regulation in the fight-or-flight response. Our results demonstrate
      that phosphorylation at Ser-1700 alone is essential to maintain basal Ca(2+)
      current and regulation by beta-adrenergic activation. As a consequence, blocking
      PKA phosphorylation at this site impairs cardiovascular physiology in vivo,
      leading to reduced exercise capacity in the fight-or-flight response and
      development of cardiac hypertrophy. 

PMID- 25368182
TI  - Disentangling the effects of CO2 and short-lived climate forcer mitigation.
AB  - Anthropogenic global warming is driven by emissions of a wide variety of
      radiative forcers ranging from very short-lived climate forcers (SLCFs), like
      black carbon, to very long-lived, like CO2. These species are often released from
      common sources and are therefore intricately linked. However, for reasons of
      simplification, this CO2-SLCF linkage was often disregarded in long-term
      projections of earlier studies. Here we explicitly account for CO2-SLCF linkages
      and show that the short- and long-term climate effects of many SLCF measures
      consistently become smaller in scenarios that keep warming to below 2  degrees C
      relative to preindustrial levels. Although long-term mitigation of methane and
      hydrofluorocarbons are integral parts of 2  degrees C scenarios, early action on
      these species mainly influences near-term temperatures and brings small benefits
      for limiting maximum warming relative to comparable reductions taking place
      later. Furthermore, we find that maximum 21st-century warming in 2  degrees C
      consistent scenarios is largely unaffected by additional black-carbon-related
      measures because key emission sources are already phased-out through CO2
      mitigation. Our study demonstrates the importance of coherently considering CO2
      SLCF coevolutions. Failing to do so leads to strongly and consistently
      overestimating the effect of SLCF measures in climate stabilization scenarios.
      Our results reinforce that SLCF measures are to be considered complementary
      rather than a substitute for early and stringent CO2 mitigation. Near-term SLCF
      measures do not allow for more time for CO2 mitigation. We disentangle and
      resolve the distinct benefits across different species and therewith facilitate
      an integrated strategy for mitigating both short and long-term climate change. 

PMID- 25368183
TI  - Acceleration of evolutionary spread by long-range dispersal.
AB  - The spreading of evolutionary novelties across populations is the central element
      of adaptation. Unless populations are well mixed (like bacteria in a shaken test
      tube), the spreading dynamics depend not only on fitness differences but also on
      the dispersal behavior of the species. Spreading at a constant speed is generally
      predicted when dispersal is sufficiently short ranged, specifically when the
      dispersal kernel falls off exponentially or faster. However, the case of long
      range dispersal is unresolved: Although it is clear that even rare long-range
      jumps can lead to a drastic speedup--as air-traffic-mediated epidemics show--it
      has been difficult to quantify the ensuing stochastic dynamical process. However,
      such knowledge is indispensable for a predictive understanding of many spreading
      processes in natural populations. We present a simple iterative scaling
      approximation supported by simulations and rigorous bounds that accurately
      predicts evolutionary spread, which is determined by a trade-off between
      frequency and potential effectiveness of long-distance jumps. In contrast to the
      exponential laws predicted by deterministic "mean-field" approximations, we show
      that the asymptotic spatial growth is according to either a power law or a
      stretched exponential, depending on the tails of the dispersal kernel. More
      importantly, we provide a full time-dependent description of the convergence to
      the asymptotic behavior, which can be anomalously slow and is relevant even for
      long times. Our results also apply to spreading dynamics on networks with a
      spectrum of long-range links under certain conditions on the probabilities of
      long-distance travel: These are relevant for the spread of epidemics.

PMID- 25368184
TI  - Single gene insertion drives bioalcohol production by a thermophilic archaeon.
AB  - Bioethanol production is achieved by only two metabolic pathways and only at
      moderate temperatures. Herein a fundamentally different synthetic pathway for
      bioalcohol production at 70  degrees C was constructed by insertion of the gene
      for bacterial alcohol dehydrogenase (AdhA) into the archaeon Pyrococcus furiosus.
      The engineered strain converted glucose to ethanol via acetate and acetaldehyde,
      catalyzed by the host-encoded aldehyde ferredoxin oxidoreductase (AOR) and
      heterologously expressed AdhA, in an energy-conserving, redox-balanced pathway.
      Furthermore, the AOR/AdhA pathway also converted exogenously added aliphatic and
      aromatic carboxylic acids to the corresponding alcohol using glucose, pyruvate,
      and/or hydrogen as the source of reductant. By heterologous coexpression of a
      membrane-bound carbon monoxide dehydrogenase, CO was used as a reductant for
      converting carboxylic acids to alcohols. Redirecting the fermentative metabolism
      of P. furiosus through strategic insertion of foreign genes creates unprecedented
      opportunities for thermophilic bioalcohol production. Moreover, the AOR/AdhA
      pathway is a potentially game-changing strategy for syngas fermentation,
      especially in combination with carbon chain elongation pathways. 

PMID- 25368185
TI  - Genetic activation of pyruvate dehydrogenase alters oxidative substrate selection
      to induce skeletal muscle insulin resistance.
AB  - The pyruvate dehydrogenase complex (PDH) has been hypothesized to link lipid
      exposure to skeletal muscle insulin resistance through a glucose-fatty acid cycle
      in which increased fatty acid oxidation increases acetyl-CoA concentrations,
      thereby inactivating PDH and decreasing glucose oxidation. However, whether fatty
      acids induce insulin resistance by decreasing PDH flux remains unknown. To
      genetically examine this hypothesis we assessed relative rates of pyruvate
      dehydrogenase flux/mitochondrial oxidative flux and insulin-stimulated rates of
      muscle glucose metabolism in awake mice lacking pyruvate dehydrogenase kinase 2
      and 4 [double knockout (DKO)], which results in constitutively activated PDH.
      Surprisingly, increased glucose oxidation in DKO muscle was accompanied by
      reduced insulin-stimulated muscle glucose uptake. Preferential myocellular
      glucose utilization in DKO mice decreased fatty acid oxidation, resulting in
      increased reesterification of acyl-CoAs into diacylglycerol and triacylglycerol,
      with subsequent activation of PKC-theta and inhibition of insulin signaling in
      muscle. In contrast, other putative mediators of muscle insulin resistance,
      including muscle acylcarnitines, ceramides, reactive oxygen species production,
      and oxidative stress markers, were not increased. These findings demonstrate that
      modulation of oxidative substrate selection to increase muscle glucose
      utilization surprisingly results in muscle insulin resistance, offering genetic
      evidence against the glucose-fatty acid cycle hypothesis of muscle insulin
      resistance. 

PMID- 25368186
TI  - Molecular insights into DNA interference by CRISPR-associated nuclease-helicase
      Cas3.
AB  - Mobile genetic elements in bacteria are neutralized by a system based on
      clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR
      associated (Cas) proteins. Type I CRISPR-Cas systems use a "Cascade"
      ribonucleoprotein complex to guide RNA specifically to complementary sequence in
      invader double-stranded DNA (dsDNA), a process called "interference." After
      target recognition by Cascade, formation of an R-loop triggers recruitment of a
      Cas3 nuclease-helicase, completing the interference process by destroying the
      invader dsDNA. To elucidate the molecular mechanism of CRISPR interference, we
      analyzed crystal structures of Cas3 from the bacterium Thermobaculum terrenum,
      with and without a bound ATP analog. The structures reveal a histidine-aspartate
      (HD)-type nuclease domain fused to superfamily-2 (SF2) helicase domains and a
      distinct C-terminal domain. Binding of ATP analog at the interface of the SF2
      helicase RecA-like domains rearranges a motif V with implications for the enzyme
      mechanism. The HD-nucleolytic site contains two metal ions that are positioned at
      the end of a proposed nucleic acid-binding tunnel running through the SF2
      helicase structure. This structural alignment suggests a mechanism for 3' to 5'
      nucleolytic processing of the displaced strand of invader DNA that is coordinated
      with ATP-dependent 3' to 5' translocation of Cas3 along DNA. In agreement with
      biochemical studies, the presented Cas3 structures reveal important mechanistic
      details on the neutralization of genetic invaders by type I CRISPR-Cas systems. 

PMID- 25368187
TI  - Tissue-specific regulation and function of Grb10 during growth and neuronal
      commitment.
AB  - Growth-factor receptor bound protein 10 (Grb10) is a signal adapter protein
      encoded by an imprinted gene that has roles in growth control, cellular
      proliferation, and insulin signaling. Additionally, Grb10 is critical for the
      normal behavior of the adult mouse. These functions are paralleled by Grb10's
      unique tissue-specific imprinted expression; the paternal copy of Grb10 is
      expressed in a subset of neurons whereas the maternal copy is expressed in most
      other adult tissues in the mouse. The mechanism that underlies this switch
      between maternal and paternal expression is still unclear, as is the role for
      paternally expressed Grb10 in neurons. Here, we review recent work and present
      complementary data that contribute to the understanding of Grb10 gene regulation
      and function, with specific emphasis on growth and neuronal development.
      Additionally, we show that in vitro differentiation of mouse embryonic stem cells
      into alpha motor neurons recapitulates the switch from maternal to paternal
      expression observed during neuronal development in vivo. We postulate that this
      switch in allele-specific expression is related to the functional role of Grb10
      in motor neurons and other neuronal tissues. 

PMID- 25368188
TI  - Isotopic signals of summer denitrification in a northern hardwood forested
      catchment.
AB  - Despite decades of measurements, the nitrogen balance of temperate forest
      catchments remains poorly understood. Atmospheric nitrogen deposition often
      greatly exceeds streamwater nitrogen losses; the fate of the remaining nitrogen
      is highly uncertain. Gaseous losses of nitrogen to denitrification are especially
      poorly documented and are often ignored. Here, we provide isotopic evidence
      (delta(15)NNO3 and delta(18)ONO3) from shallow groundwater at the Hubbard Brook
      Experimental Forest indicating extensive denitrification during midsummer, when
      transient, perched patches of saturation developed in hillslopes, with poor
      hydrological connectivity to the stream, while streamwater showed no isotopic
      evidence of denitrification. During small rain events, precipitation directly
      contributed up to 34% of streamwater nitrate, which was otherwise produced by
      nitrification. Together, these measurements reveal the importance of
      denitrification in hydrologically disconnected patches of shallow groundwater
      during midsummer as largely overlooked control points for nitrogen loss from
      temperate forest catchments. 

PMID- 25368189
TI  - Far-infrared surface emissivity and climate.
AB  - Presently, there are no global measurement constraints on the surface emissivity
      at wavelengths longer than 15 MUm, even though this surface property in this far
      IR region has a direct impact on the outgoing longwave radiation (OLR) and
      infrared cooling rates where the column precipitable water vapor (PWV) is less
      than 1 mm. Such dry conditions are common for high-altitude and high-latitude
      locations, with the potential for modeled climate to be impacted by uncertain
      surface characteristics. This paper explores the sensitivity of instantaneous OLR
      and cooling rates to changes in far-IR surface emissivity and how this
      unconstrained property impacts climate model projections. At high latitudes and
      altitudes, a 0.05 change in emissivity due to mineralogy and snow grain size can
      cause a 1.8-2.0 W m(-2) difference in the instantaneous clear-sky OLR. A variety
      of radiative transfer techniques have been used to model the far-IR spectral
      emissivities of surface types defined by the International Geosphere-Biosphere
      Program. Incorporating these far-IR surface emissivities into the Representative
      Concentration Pathway (RCP) 8.5 scenario of the Community Earth System Model
      leads to discernible changes in the spatial patterns of surface temperature, OLR,
      and frozen surface extent. The model results differ at high latitudes by as much
      as 2 degrees K, 10 W m(-2), and 15%, respectively, after only 25 y of
      integration. Additionally, the calculated difference in far-IR emissivity between
      ocean and sea ice of between 0.1 and 0.2, suggests the potential for a far-IR
      positive feedback for polar climate change. 

PMID- 25368190
TI  - Metabolic sensor governing bacterial virulence in Staphylococcus aureus.
AB  - An effective metabolism is essential to all living organisms, including the
      important human pathogen Staphylococcus aureus. To establish successful
      infection, S. aureus must scavenge nutrients and coordinate its metabolism for
      proliferation. Meanwhile, it also must produce an array of virulence factors to
      interfere with host defenses. However, the ways in which S. aureus ties its
      metabolic state to its virulence regulation remain largely unknown. Here we show
      that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, binds
      to and activates the catabolite control protein E (CcpE) of S. aureus. Using
      structural and site-directed mutagenesis studies, we demonstrate that two
      arginine residues (Arg145 and Arg256) within the putative inducer-binding cavity
      of CcpE are important for its allosteric activation by citrate. Microarray
      analysis reveals that CcpE tunes the expression of 126 genes that comprise about
      4.7% of the S. aureus genome. Intriguingly, although CcpE is a major positive
      regulator of the TCA-cycle activity, its regulon consists predominantly of genes
      involved in the pathogenesis of S. aureus. Moreover, inactivation of CcpE results
      in increased staphyloxanthin production, improved ability to acquire iron,
      increased resistance to whole-blood-mediated killing, and enhanced bacterial
      virulence in a mouse model of systemic infection. This study reveals CcpE as an
      important metabolic sensor that allows S. aureus to sense and adjust its
      metabolic state and subsequently to coordinate the expression of virulence
      factors and bacterial virulence. 

PMID- 25368191
TI  - Microtubules stabilize cell polarity by localizing rear signals.
AB  - Microtubules are known to play an important role in cell polarity; however, the
      mechanism remains unclear. Using cells migrating persistently on micropatterned
      strips, we found that depolymerization of microtubules caused cells to change
      from persistent to oscillatory migration. Mathematical modeling in the context of
      a local-excitation-global-inhibition control mechanism indicated that this
      mechanism can account for microtubule-dependent oscillation, assuming that
      microtubules remove inhibitory signals from the front after a delayed generation.
      Experiments further supported model predictions that the period of oscillation
      positively correlates with cell length and that oscillation may be induced by
      inhibiting retrograde motors. We suggest that microtubules are required not for
      the generation but for the maintenance of cell polarity, by mediating the global
      distribution of inhibitory signals. Disassembly of microtubules induces cell
      oscillation by allowing inhibitory signals to accumulate at the front, which
      stops frontal protrusion and allows the polarity to reverse. 

PMID- 25368193
TI  - Prevalence of cycling genes and drug targets calls for prospective
      chronotherapeutics.

PMID- 25368192
TI  - Sex disparity in colonic adenomagenesis involves promotion by male hormones, not
      protection by female hormones.
AB  - It recently has been recognized that men develop colonic adenomas and carcinomas
      at an earlier age and at a higher rate than women. In the Apc(Pirc/+) (Pirc) rat
      model of early colonic cancer, this sex susceptibility was recapitulated, with
      male Pirc rats developing twice as many adenomas as females. Analysis of large
      datasets revealed that the Apc(Min/+) mouse also shows enhanced male
      susceptibility to adenomagenesis, but only in the colon. In addition, WT mice
      treated with injections of the carcinogen azoxymethane (AOM) showed increased
      numbers of colonic adenomas in males. The mechanism underlying these observations
      was investigated by manipulation of hormonal status. The preponderance of colonic
      adenomas in the Pirc rat model allowed a statistically significant investigation
      in vivo of the mechanism of sex hormone action on the development of colonic
      adenomas. Females depleted of endogenous hormones by ovariectomy did not exhibit
      a change in prevalence of adenomas, nor was any effect observed with replacement
      of one or a combination of female hormones. In contrast, depletion of male
      hormones by orchidectomy (castration) markedly protected the Pirc rat from
      adenoma development, whereas supplementation with testosterone reversed that
      effect. These observations were recapitulated in the AOM mouse model. Androgen
      receptor was undetectable in the colon or adenomas, making it likely that
      testosterone acts indirectly on the tumor lineage. Our findings suggest that
      indirect tumor-promoting effects of testosterone likely explain the disparity
      between the sexes in the development of colonic adenomas. 

PMID- 25368194
TI  - siRNAs from an X-linked satellite repeat promote X-chromosome recognition in
      Drosophila melanogaster.
AB  - Highly differentiated sex chromosomes create a lethal imbalance in gene
      expression in one sex. To accommodate hemizygosity of the X chromosome in male
      fruit flies, expression of X-linked genes increases twofold. This is achieved by
      the male- specific lethal (MSL) complex, which modifies chromatin to increase
      expression. Mutations that disrupt the X localization of this complex decrease
      the expression of X-linked genes and reduce male survival. The mechanism that
      restricts the MSL complex to X chromatin is not understood. We recently reported
      that the siRNA pathway contributes to localization of the MSL complex, raising
      questions about the source of the siRNAs involved. The X-linked 1.688 g/cm(3)
      satellite related repeats (1.688(X) repeats) are restricted to the X chromosome
      and produce small RNA, making them an attractive candidate. We tested RNA from
      these repeats for a role in dosage compensation and found that ectopic expression
      of single-stranded RNAs from 1.688(X) repeats enhanced the male lethality of
      mutants with defective X recognition. In contrast, expression of double-stranded
      hairpin RNA from a 1.688(X) repeat generated abundant siRNA and dramatically
      increased male survival. Consistent with improved survival, X localization of the
      MSL complex was largely restored in these males. The striking distribution of
      1.688(X) repeats, which are nearly exclusive to the X chromosome, suggests that
      these are cis-acting elements contributing to identification of X chromatin. 

PMID- 25368195
TI  - Impact of early-stage HIV transmission on treatment as prevention.

PMID- 25368196
TI  - Amino acid modified Ni catalyst exhibits reversible H2 oxidation/production over
      a broad pH range at elevated temperatures.
AB  - Hydrogenases interconvert H2 and protons at high rates and with high energy
      efficiencies, providing inspiration for the development of molecular catalysts.
      Studies designed to determine how the protein scaffold can influence a
      catalytically active site have led to the synthesis of amino acid derivatives of
      [Ni(P2(R)N2(R'))2](2+) complexes, [Ni(P2(Cy)N2(Amino acid))2](2+) (CyAA). It is
      shown that these CyAA derivatives can catalyze fully reversible H2
      production/oxidation at rates approaching those of hydrogenase enzymes. The
      reversibility is achieved in acidic aqueous solutions (pH = 0-6), 1 atm 25%
      H2/Ar, and elevated temperatures (tested from 298 to 348 K) for the glycine
      (CyGly), arginine (CyArg), and arginine methyl ester (CyArgOMe) derivatives. As
      expected for a reversible process, the catalytic activity is dependent upon H2
      and proton concentrations. CyArg is significantly faster in both directions (~300
      s(-1) H2 production and 20 s(-1) H2 oxidation; pH = 1, 348 K, 1 atm 25% H2/Ar)
      than the other two derivatives. The slower turnover frequencies for CyArgOMe (35
      s(-1) production and 7 s(-1) oxidation under the same conditions) compared with
      CyArg suggests an important role for the COOH group during catalysis. That CyArg
      is faster than CyGly (3 s(-1) production and 4 s(-1) oxidation) suggests that the
      additional structural features imparted by the guanidinium groups facilitate fast
      and reversible H2 addition/release. These observations demonstrate that outer
      coordination sphere amino acids work in synergy with the active site and can play
      an important role for synthetic molecular electrocatalysts, as has been observed
      for the protein scaffold of redox active enzymes.

PMID- 25368198
TI  - Cells infected with herpes simplex virus 1 export to uninfected cells exosomes
      containing STING, viral mRNAs, and microRNAs.
AB  - STING (stimulator of IFN genes) activates the IFN-dependent innate immune
      response to infection on sensing the presence of DNA in cytosol. The quantity of
      STING accumulating in cultured cells varies; it is relatively high in some cell
      lines [e.g., HEp-2, human embryonic lung fibroblasts (HEL), and HeLa] and low in
      others (e.g., Vero cells). In a preceding publication we reported that STING was
      stable in four cell lines infected with herpes simplex virus 1 and that it was
      actively stabilized in at least two cell lines derived from human cancers. In
      this report we show that STING is exported from HEp-2 cells to Vero cells along
      with virions, viral mRNAs, microRNAs, and the exosome marker protein CD9. The
      virions and exosomes copurified. The quantity of STING and CD9 exported from one
      cell line to another was inoculum-size-dependent and reflected the levels of
      STING and CD9 accumulating in the cells in which the virus inoculum was made. The
      export of STING, an innate immune sensor, and of viral mRNAs whose major role may
      be in silencing viral genes in latently infected neurons, suggests that the virus
      has evolved mechanisms that curtail rather than foster the spread of infection
      under certain conditions. 

PMID- 25368197
TI  - Rapid diversification of five Oryza AA genomes associated with rice adaptation.
AB  - Comparative genomic analyses among closely related species can greatly enhance
      our understanding of plant gene and genome evolution. We report de novo-assembled
      AA-genome sequences for Oryza nivara, Oryza glaberrima, Oryza barthii, Oryza
      glumaepatula, and Oryza meridionalis. Our analyses reveal massive levels of
      genomic structural variation, including segmental duplication and rapid gene
      family turnover, with particularly high instability in defense-related genes. We
      show, on a genomic scale, how lineage-specific expansion or contraction of gene
      families has led to their morphological and reproductive diversification, thus
      enlightening the evolutionary process of speciation and adaptation. Despite
      strong purifying selective pressures on most Oryza genes, we documented a large
      number of positively selected genes, especially those genes involved in flower
      development, reproduction, and resistance-related processes. These diversifying
      genes are expected to have played key roles in adaptations to their ecological
      niches in Asia, South America, Africa and Australia. Extensive variation in
      noncoding RNA gene numbers, function enrichment, and rates of sequence divergence
      might also help account for the different genetic adaptations of these rice
      species. Collectively, these resources provide new opportunities for evolutionary
      genomics, numerous insights into recent speciation, a valuable database of
      functional variation for crop improvement, and tools for efficient conservation
      of wild rice germplasm. 

PMID- 25368199
TI  - Decreased segregation of brain systems across the healthy adult lifespan.
AB  - Healthy aging has been associated with decreased specialization in brain
      function. This characterization has focused largely on describing age-accompanied
      differences in specialization at the level of neurons and brain areas. We expand
      this work to describe systems-level differences in specialization in a healthy
      adult lifespan sample (n = 210; 20-89 y). A graph-theoretic framework is used to
      guide analysis of functional MRI resting-state data and describe systems-level
      differences in connectivity of individual brain networks. Young adults' brain
      systems exhibit a balance of within- and between-system correlations that is
      characteristic of segregated and specialized organization. Increasing age is
      accompanied by decreasing segregation of brain systems. Compared with systems
      involved in the processing of sensory input and motor output, systems mediating
      "associative" operations exhibit a distinct pattern of reductions in segregation
      across the adult lifespan. Of particular importance, the magnitude of association
      system segregation is predictive of long-term memory function, independent of an
      individual's age. 

PMID- 25368201
TI  - Reply to Hedrick et al.: Trophy hunting influences the distribution of trait
      values through demographic impacts.

PMID- 25368200
TI  - Spatial embedding of structural similarity in the cerebral cortex.
AB  - Recent anatomical tracing studies have yielded substantial amounts of data on the
      areal connectivity underlying distributed processing in cortex, yet the
      fundamental principles that govern the large-scale organization of cortex remain
      unknown. Here we show that functional similarity between areas as defined by the
      pattern of shared inputs or outputs is a key to understanding the areal network
      of cortex. In particular, we report a systematic relation in the monkey, human,
      and mouse cortex between the occurrence of connections from one area to another
      and their similarity distance. This characteristic relation is rooted in the
      wiring distance dependence of connections in the brain. We introduce a weighted,
      spatially embedded random network model that robustly gives rise to this
      structure, as well as many other spatial and topological properties observed in
      cortex. These include features that were not accounted for in any previous model,
      such as the wide range of interareal connection weights. Connections in the model
      emerge from an underlying distribution of spatially embedded axons, thereby
      integrating the two scales of cortical connectivity--individual axons and
      interareal pathways--into a common geometric framework. These results provide
      insights into the origin of large-scale connectivity in cortex and have important
      implications for theories of cortical organization.

PMID- 25368202
TI  - Prognostic importance of temporal changes in resting heart rate in heart failure
      patients: an analysis of the CHARM program.
AB  - BACKGROUND: Resting heart rate (HR) is a predictor of adverse outcome in patients
      with heart failure (HF). Whether changes in HR over time in patients with chronic
      HF are also associated with adverse outcome is unknown. We explored the
      relationship between changes in HR from a preceding visit, time-updated HR (i.e.
      most recent available HR value from a clinic visit) and subsequent outcomes in
      patients with chronic HF. METHODS AND RESULTS: We studied 7599 patients enrolled
      in the candesartan in heart failure: assessment of reduction in mortality and
      morbidity program. We calculated change in HR from the preceding visit and
      explored its association with outcomes in Cox proportional hazards models, as
      well the association between time-updated HR and outcome. An increase in HR from
      preceding visit was associated with a higher risk of all-cause mortality and the
      composite endpoint of cardiovascular death or hospitalization for HF (adjusted
      hazard ratio 1.06, 95% confidence intervals, CI: 1.05-1.08, P < 0.001, per 5
      b.p.m. higher HR), with lowering of HR being associated with lower risk,
      adjusting for covariates, including time-updated beta-blocker dose and baseline
      HR. Time-updated resting HR at each visit was also associated with risk (adjusted
      hazard ratio 1.07, 95% CI: 1.06-1.09; P < 0.001, per 5 b.p.m. higher HR).
      CONCLUSIONS: Change in HR over time predicts outcome in patients with chronic HF,
      as does time-updated HR during follow-up. These data suggest that frequent
      outpatient monitoring of HR, and identification of changes over time, possibly
      with remote technologies, may identify patients with HF who may be at increased
      risk of rehospitalization or death.

PMID- 25368204
TI  - Late intracardiac orthopedic wire migration presenting as tamponade and stroke.

PMID- 25368203
TI  - Pravastatin reverses obesity-induced dysfunction of induced pluripotent stem cell
      derived endothelial cells via a nitric oxide-dependent mechanism.
AB  - AIMS: High-fat diet-induced obesity (DIO) is a major contributor to type II
      diabetes and micro- and macro-vascular complications leading to peripheral
      vascular disease (PVD). Metabolic abnormalities of induced pluripotent stem cell
      derived endothelial cells (iPSC-ECs) from obese individuals could potentially
      limit their therapeutic efficacy for PVD. The aim of this study was to compare
      the function of iPSC-ECs from normal and DIO mice using comprehensive in vitro
      and in vivo assays. METHODS AND RESULTS: Six-week-old C57Bl/6 mice were fed with
      a normal or high-fat diet. At 24 weeks, iPSCs were generated from tail tip
      fibroblasts and differentiated into iPSC-ECs using a directed monolayer approach.
      In vitro functional analysis revealed that iPSC-ECs from DIO mice had
      significantly decreased capacity to form capillary-like networks, diminished
      migration, and lower proliferation. Microarray and ELISA confirmed elevated
      apoptotic, inflammatory, and oxidative stress pathways in DIO iPSC-ECs. Following
      hindlimb ischaemia, mice receiving intramuscular injections of DIO iPSC-ECs had
      significantly decreased reperfusion compared with mice injected with control
      healthy iPSC-ECs. Hindlimb sections revealed increased muscle atrophy and
      presence of inflammatory cells in mice receiving DIO iPSC-ECs. When pravastatin
      was co-administered to mice receiving DIO iPSC-ECs, a significant increase in
      reperfusion was observed; however, this beneficial effect was blunted by co
      administration of the nitric oxide synthase inhibitor, N(omega)-nitro-l-arginine
      methyl ester. CONCLUSION: This is the first study to provide evidence that iPSC
      ECs from DIO mice exhibit signs of endothelial dysfunction and have suboptimal
      efficacy following transplantation in a hindlimb ischaemia model. These findings
      may have important implications for future treatment of PVD using iPSC-ECs in the
      obese population.

PMID- 25368205
TI  - Oral anticoagulation therapy after radiofrequency ablation of atrial fibrillation
      and the risk of thromboembolism and serious bleeding: long-term follow-up in
      nationwide cohort of Denmark.
AB  - AIM: To investigate the long-term risk of thromboembolism and serious bleeding
      associated with oral anticoagulation (OAC) therapy beyond 3 months after
      radiofrequency ablation (RFA) of atrial fibrillation (AF). METHODS AND RESULTS:
      Linking Danish administrative registries, 4050 patients undergoing first-time RFA
      (2000-11) were identified. Risk of thromboembolism and serious bleeding according
      to OAC therapy were analysed by incidence rates (presented per 100 person-years)
      and Cox proportional-hazard models. The median age was 59.5 years (interquartile
      range, IQR: 52.8-65.2); 26.5% were females. During a median follow-up of 3.4
      years (IQR: 2.0-5.6), 71 (1.8%) thromboembolism cases were identified, where
      incidence rates with and without OAC were 0.56 (0.40-0.78)95%CI and 0.64 (0.46
      0.89)95%CI, respectively. Oral anticoagulation discontinuation remained
      insignificant [hazard ratio 1.42(0.86-2.35)95%CI] in multivariable analysis.
      Beyond 3 months after RFA 87 (2.1%) serious bleedings occurred; incidence rates
      with and without OAC were 0.99 (0.77-1.27)95%CI and 0.44 (0.29-0.65)95%CI,
      respectively. Oral anticoagulation therapy was significantly associated with
      serious bleeding risk [hazard ratio 2.05(1.25-3.35)95%CI]. In an age- and gender
      matched cohort (1 : 4) of 15 848 non-ablated AF patients receiving rhythm-control
      therapy, thromboembolic rates with and without OAC were 1.34 (1.21-1.49)95%CI and
      2.14 (1.98-2.30)95%CI, respectively. Adjusted incidence rate ratio was 0.53 (0.43
      0.65)95%CI favouring RFA cohort. CONCLUSION: Thromboembolic risk beyond 3 months
      after RFA was relatively low compared with a matched non-ablated AF cohort. With
      cautious interpretation due to low number of events, serious bleeding risk
      associated with OAC seems to outweigh the benefits of thromboembolic risk
      reduction. Randomized studies are warranted to test our results.

PMID- 25368206
TI  - Redox-active compounds with a history of human use: antistaphylococcal action and
      potential for repurposing as topical antibiofilm agents.
AB  - OBJECTIVES: To investigate the antistaphylococcal/antibiofilm activity and mode
      of action (MOA) of a panel of redox-active (RA) compounds with a history of human
      use and to provide a preliminary preclinical assessment of their potential for
      topical treatment of staphylococcal infections, including those involving a
      biofilm component. METHODS: Antistaphylococcal activity was evaluated by broth
      microdilution and by time-kill studies with growing and slow- or non-growing
      cells. The antibiofilm activity of RA compounds, alone and in combination with
      established antibacterial agents, was assessed using the Calgary Biofilm Device.
      Established assays were used to examine the membrane-perturbing effects of RA
      compounds, to measure penetration into biofilms and physical disruption of
      biofilms and to assess resistance potential. A living skin equivalent model was
      used to assess the effects of RA compounds on human skin. RESULTS: All 15 RA
      compounds tested displayed antistaphylococcal activity against planktonic
      cultures (MIC 0.25-128 mg/L) and 7 eradicated staphylococcal biofilms (minimum
      biofilm eradication concentration 4-256 mg/L). The MOA of all compounds involved
      perturbation of the bacterial membrane, whilst selected compounds with
      antibiofilm activity caused destructuring of the biofilm matrix. The two most
      promising agents [celastrol and nordihydroguaiaretic acid (NDGA)] in respect of
      antibacterial potency and selective toxicity against bacterial membranes acted
      synergistically with gentamicin against biofilms, did not damage artificial skin
      following topical application and exhibited low resistance potential.
      CONCLUSIONS: In contrast to established antibacterial drugs, some RA compounds
      are capable of eradicating staphylococcal biofilms. Of these, celastrol and NDGA
      represent particularly attractive candidates for development as topical
      antistaphylococcal biofilm treatments.

PMID- 25368207
TI  - Relationship of left ventricular mass to coronary atherosclerosis and myocardial
      ischaemia: the CORE320 multicenter study.
AB  - AIMS: The aim of this study was to investigate the association of left
      ventricular mass (LVM) with coronary atherosclerosis and myocardial infarction
      (MI). METHODS AND RESULTS: Patients (n = 338) underwent 320 * 0.5 mm detector row
      coronary computed tomography (CT) angiography, invasive coronary angiography
      (ICA), and single-photon emission CT (SPECT) myocardial perfusion imaging.
      Quantitative coronary atheroma volume was obtained from the CT images for the
      entire coronary tree (19-segment model) with an arterial contour detection
      algorithm. Normalized total atheroma volume (NormTAV) was analysed to reflect
      quantitative total atheroma volume. LVM was measured on myocardial CT images and
      indexed to height to the power of 2.7 (LVMi). Patients with obstructive coronary
      artery disease (CAD) were defined as those with >=50% diameter stenosis by
      quantitative ICA. Abnormal perfusion defect was defined as >=1 abnormal
      myocardial segment by SPECT. The association of LVMi with coronary
      atherosclerosis and myocardial perfusion defect on SPECT at the patient level was
      determined with uni- and multivariable linear and logistic regression analyses.
      Obstructive CAD was present in 60.0% of enrolled patients. LVMi was independently
      associated with abnormal summed rest score [SRS; odds ratio (OR), 1.07; 95%
      confidence interval (CI), 1.03-1.09] and summed stress score (OR, 1.04; 95% CI,
      1.01-1.07). An increase in LVMi was also independently associated with that in
      NormTAV (coefficient, 10.44; 95% CI, 1.50-19.39) and SRS >=1 (OR, 1.05; 95% CI,
      1.01-1.10), even after adjusting for cardiovascular risk factors in patients
      without previous MI. CONCLUSIONS: LVM was independently associated with the
      presence of coronary artery atherosclerosis and MI.

PMID- 25368208
TI  - Leaflet remodelling in functional mitral valve regurgitation: characteristics,
      determinants, and relation to regurgitation severity.
AB  - BACKGROUND: Recently, it has been hypothesized that mitral leaflet remodelling
      may play a role in the pathophysiology of functional mitral regurgitation (FMR).
      We investigated the characteristics, determinants, and relation of mitral leaflet
      remodelling to FMR severity. METHODS AND RESULTS: Three-dimensional
      transoesophageal echocardiographic data of the mitral valve (MV) were studied in
      30 patients with FMR >= grade 3 (>=3), 24 patients with FMR < grade 3 (<3), and
      22 controls with normal MV. FMR <3 and >=3 patients showed leaflet remodelling
      compared with control subjects with larger overall MV leaflet areas (11.47 +/-
      3.16 and 9.58 +/- 1.99 vs. 7.30 +/- 1.57 cm(2)/m(2), respectively; all P < 0.01).
      Tenting volume (r(2) = 0.55), left ventricular (LV) ejection fraction (r(2) =
      0.20), annulus area (r(2) = 0.87), and LV sphericity index (r(2) = 0.25) were
      correlated with overall MV leaflet area (all P < 0.001). Although these
      correlates were similar between FMR <3 and >=3 patients (all P > 0.05), the
      overall MV leaflet area was smaller in FMR >=3 compared with FMR <3 patients (P =
      0.01), indicating less remodelling despite similar tethering degree.
      Particularly, coaptation/overall MV leaflet area ratio <=0.24, reflecting
      insufficient leaflet remodelling, was associated with FMR >=3 [area under
      receiver operating characteristic (ROC) curve = 0.93, sensitivity 90%, and
      specificity 91%]. This ratio was independently associated with FMR >=3 (odds
      ratio 70.0, 95% confidence interval 11.7-419.9, P < 0.001) and showed significant
      correlation with effective regurgitant orifice area (r(2) = 0.38, P < 0.001).
      CONCLUSION: MV leaflet remodelling in FMR is common and relates to LV function,
      LV sphericity, MV tenting volume, and annulus dilatation. Insufficient leaflet
      remodelling relative to the mitral annular and LV changes is independently
      associated with FMR severity.

PMID- 25368209
TI  - Food and Drug Administration criteria for the diagnosis of drug-induced valvular
      heart disease in patients previously exposed to benfluorex: a prospective
      multicentre study.
AB  - AIMS: The Food and Drug Administration (FDA) criteria for diagnosis of drug
      induced valvular heart disease (DIVHD) are only based on the observation of
      aortic regurgitation >= mild and/or mitral regurgitation >= moderate. We sought
      to evaluate the diagnostic value of FDA criteria in a cohort of control patients
      and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD.
      METHODS AND RESULTS: This prospective, multicentre study included 376 diabetic
      control patients not exposed to valvulopathic drugs and 1000 subjects previously
      exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a
      combined functional and morphological echocardiographic analysis of cardiac
      valves. Patients were classified according to the FDA criteria [mitral or aortic
      FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were
      wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of
      false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a
      diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the
      910 patients (99%) without a diagnosis of the mitral DIVHD group were classified
      as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were
      classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of
      aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were
      independent predictors of disagreement between FDA criteria and the diagnosis of
      DIVHD in patients exposed to benfluorex (both P <= 0.001). CONCLUSIONS: FDA
      criteria solely based on the Doppler detection of cardiac valve regurgitation
      underestimate for the mitral valve and overestimate for the aortic valve the
      frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined
      echocardiographic and Doppler morphological and functional analysis of cardiac
      valves.

PMID- 25368211
TI  - Chronic adaptation of atrial structure and function in elite male athletes.
AB  - AIMS: The aim of this study was to establish the degree of structural and
      functional adaptations in the left (LA) and right atria (RA) in elite male
      athletes engaged in 'high dynamic : high static' (HDHS) and 'low dynamic : high
      static' (LDHS) sporting disciplines compared with sedentary controls. METHODS AND
      RESULTS: Eighteen male, elite HDHS athletes (13 boxers and 7 triathletes), 18
      male, elite LDHS athletes (8 weightlifters and 10 Akido), and 20 male, age
      matched sedentary controls were assessed using conventional 2D and myocardial
      speckle tracking (MST) echocardiography. Absolute LA and RA volumes [end systole
      (VOLes), pre A (VOLpreA), and end diastole (VOLed)] as well as the functional
      indices of reservoir (RESvol), conduit (CONvol), and booster volumes (BOOvol)
      were defined. MST allowed the assessment of atrial strain (epsilon) during the
      reservoir (RESepsilon), conduit (CONepsilon), and booster (BOOepsilon) phases of
      the cardiac cycle. Both LA and RA sizes were significantly larger in HDHS
      compared with LDHS and controls (P < 0.05) across all structural and functional
      volume parameters with no significant difference between LDHS and controls
      (LAVOLes 35 +/- 8, 26 +/- 10, and 23 +/- 5 mL/m(2); RAVOLes 37 +/- 10, 26 +/- 9,
      and 23 +/- 5 mL/m(2), LARESvol 35 +/- 9, 25 +/- 11, and 23 +/- 7 mL; RARESvol 41
      +/- 11, 34 +/- 11, and 28 +/- 7 mL for HDHS, LDHS, and controls, respectively).
      RA : LA ratios were >1 in all groups due to a comparatively larger RA volume
      (RAVOLes : LAVOLes 1.05 +/- 0.26, 1.12 +/- 0.55, and 1.04 +/- 0.28 for HDHS,
      LDHS, and controls, respectively, P > 0.05). There was no significant between
      group differences for any epsilon parameter. CONCLUSION: Bi-atrial hypertrophy is
      demonstrated in HDHS athletes and not in LDHS athletes, suggesting that the
      dynamic component to training is the primary driver for both LA and RA
      adaptation. Although functional data derived from volume shifts suggest augmented
      function in HDHS athletes, MST imaging demonstrated no difference in intrinsic
      atrial epsilon in any of the groups.

PMID- 25368210
TI  - Normal values and clinical relevance of left atrial myocardial function analysed
      by speckle-tracking echocardiography: multicentre study.
AB  - AIMS: The aim of this multicentre study was to determine the normal range and the
      clinical relevance of the myocardial function of the left atrium (LA) analysed by
      2D speckle-tracking echocardiography (2DSTE). METHODS AND RESULTS: We analysed
      329 healthy adult subjects prospectively included in 10 centres and a validation
      group of 377 patients with left ventricular diastolic dysfunction (LVDD). LA
      myocardial function was analysed by LA strain rate peak during LA contraction (LA
      SRa) and LA strain peak during LA relaxation (LA-Strain). The range of values of
      LA myocardial function in healthy subjects was LA-SRa -2.11 +/- 0.61 s(-1) and LA
      Strain 45.5 +/- 11.4%, and the lowest expected values of these LA analyses
      (calculated as -1.96 SD from the mean of healthy subjects) were LA-SRa -0.91 s(
      1) and LA-Strain 23.1%. Concerning the clinical relevance of these LA myocardial
      analyses, LA-SRa and LA-Strain detected subtle LA dysfunction in patients with
      LVDD, even though LA volumetric measurements were normal. In addition, in these
      patients we found that the functional class (dyspnoea-NYHA classification) was
      inversely related to both LA-Strain and LA-SRa. CONCLUSION: In the present
      multicentre study analysing a large cohort of healthy subjects and patients with
      LVDD, the normal range and the clinical relevance of the myocardial function of
      the LA using 2DSTE have been determined.

PMID- 25368212
TI  - Screening guidelines: A matter of perspective.

PMID- 25368213
TI  - Six screening tests for adults: What's recommended? What's controversial?
AB  - This paper discusses guidelines from the US Preventive Services Task Force
      (USPSTF) and other recommending bodies for screening for abdominal aortic
      aneurysm and cancers of the colon, cervix, lung, breast, and prostate. 

PMID- 25368214
TI  - Miss the ear, and you may miss the diagnosis.

PMID- 25368215
TI  - Q: Does massive hemoptysis always merit diagnostic bronchoscopy?

PMID- 25368216
TI  - Why are we doing cardiovascular outcome trials in type 2 diabetes?
AB  - Cardiovascular disease is the leading cause of morbidity and death in people with
      diabetes mellitus. While worsening hyperglycemia is directly associated with
      poorer outcomes, studies aiming at euglycemia have failed to show an advantage
      over modest glucose-lowering strategies. Several diabetes drugs that were
      approved solely on the basis of their glucose-lowering potential were later shown
      to increase cardiovascular risk. 

PMID- 25368217
TI  - Diabetes management: More than just cardiovascular risk?

PMID- 25368218
TI  - A 61-year-old man with fluctuating hypertension.

PMID- 25368219
TI  - Acute respiratory distress syndrome: Implications of recent studies.
AB  - Acute respiratory distress syndrome (ARDS) remains challenging to diagnose and
      manage. This article reviews the new definition of ARDS and the key findings of
      landmark studies over the last 5 years of prone-position ventilation, high
      frequency oscillatory ventilation (HFOV), extracorporeal membrane oxygenation
      (ECMO), and neuromuscular blockade in patients with ARDS. 

PMID- 25368220
TI  - Caring for women with HIV: Unique needs and challenges.
AB  - Women infected with human immunodeficiency virus (HIV) have unique needs.
      Treatment recommendations are the same for men and women, but in women, fertility
      desires, pregnancy, contraception, and aging must be taken into account in their
      medical care. 

PMID- 25368221
TI  - Women and HIV: An expanded perspective.

PMID- 25368222
TI  - NOTCH signaling roles in acute myeloid leukemia cell growth and interaction with
      other stemness-related signals.
AB  - NOTCH activation plays oncogenic roles in acute T-lymphoblastic leukaemia (T
      ALL). However, whether NOTCH is oncogenic or tumor-suppressive in acute myeloid
      leukaemia (AML) is still controversial. Herein, the roles of NOTCH in AML are
      reviewed. AML cells express NOTCH and NOTCH ligands; however, cell-autonomous
      activation is not observed. Activating NOTCH1 mutations are rare in AML, unlike
      in T-ALL. NOTCH ligand stimulation generally suppresses the in vitro growth of
      AML cells but promotes transient growth of some samples. Conversely, knockdown of
      NOTCH1 and NOTCH2 does not affect the growth of AML cells, whereas it suppresses
      the growth of T-ALL cells. These findings suggest that NOTCH is dispensable or
      suppressive for AML cell growth. However, the effects of NOTCH differ depending
      on cell conditions, and various stemness-related signals modify these effects;
      hence, forced NOTCH activation in vitro may not exhibit effects in bone marrow.
      Thus, further understanding is required for the development of AML therapies
      targeting NOTCH signalling. 

PMID- 25368223
TI  - Resistance to abiraterone in castration-resistant prostate cancer: a review of
      the literature.
AB  - Persistent androgen signaling is functionally significant in castration-resistant
      prostate cancer (CRPC) and it is actually considered a validated therapeutic
      target. Residual intra-tumoral androgens compensate for the effects of androgen
      ablation, activating the androgen receptor (AR), AR-mediated gene expression and
      driving CRPC. The intra-tumoral biosynthesis of androgens takes place in
      different ways and cytochrome P450 17A1 (CYP17A1) has a crucial role in this
      context. Abiraterone, a CYP17A1 inhibitor, has shown impressive results in pre-
      and post-chemotherapy settings, prolonging the survival of patients with CRPC.
      However, not all patients respond to the treatment and most responders develop
      resistance, with a widely variable duration of response. Although many hypotheses
      are emerging, the mechanisms of resistance to abiraterone treatment have not yet
      been elucidated. The aim of the present review is to describe the main data
      currently available on resistance to abiraterone. 

PMID- 25368224
TI  - Surgery for symptomatic colon lipoma: a systematic review of the literature.
AB  - AIM: Isolated colon lipomas are rare benign tumors. We herein conducted a
      systematic review of the literature to identify clinical characteristic,
      diagnostic and treatment options. MATERIALS AND METHODS: A search for relevant
      studies was conducted in Scopus, Embase and Medline databases until the end of
      May 2014. The search terms were "colonic lipoma and colon lipoma". Articles were
      included if they had information on symptoms, lipoma characteristics and type of
      procedure performed. RESULTS: 88 articles describing 184 patients affected with
      colonic lipomas were found. One hundred and twenty-seven patients were selected
      for further analysis. The most common signs included abdominal pain, rectal
      bleeding and alteration in bowel habits. Colonic lipomas were frequently
      localized in the right colon (50%). The majority of patients had open surgery,
      whereas current treatment is laparoscopic resection. CONCLUSIONS: Laparoscopic
      surgery is the current standard-of-treatment of symptomatic colonic lipomas
      greater than 2 cm in diameter or when malignancy can not be preoperatively
      excluded.

PMID- 25368225
TI  - Current concepts in colorectal cancer prevention with cyclooxygenase inhibitors.
AB  - Colorectal cancer is one of the commonest malignancies worldwide. Recently, there
      has been much speculation regarding the role of cyclooxygenase-2 (COX-2)
      suppression in chemoprevention. Drugs with the ability to inhibit COX-2
      expression include aspirin, nonsteroidal anti-inflammatory drugs (NSAID) and
      selective COX-2 inhibitors. Any strategy for chemoprevention must be able to
      quantify how effective the potential treatment is likely to be and which drugs
      will be most useful. We would also need to know for how long the agent could be
      taken safely and if any side-effects could preclude long-term use. Evidence from
      observational studies and recent updates of randomised controlled trials have
      been very encouraging - at least indicating benefit from the long term use of
      aspirin, even at low dose, with greatest impact on prevention of proximal colon
      cancers and adenomas. Most studies do, however, also warn that risks of
      gastrointestinal bleeding increase with long-term use of aspirin and related
      drugs. The risk-to-benefit ratio of a chemoprevention regimen using these
      medications needs to be carefully examined. 

PMID- 25368226
TI  - Surgical management of microscopic positive resection margin after gastrectomy
      for gastric cancer: a systematic review of gastric R1 management.
AB  - BACKGROUND: The prognosis after a curative resection for gastric cancer is
      modified by the lymph node involvement, while the prognostic significance of a
      microscopically-positive resection margin is debated. We systematically reviewed
      the literature from 1998 to 2013 to describe the role of surgery in the
      management of gastric cancer with a R1 after gastrectomy. MATERIALS AND METHODS:
      The research was systematically performed on Pubmed, EMbase, Cochrane Library,
      CILEA Archive, BMJ Clinical Evidence and Up ToDate databases. Twelve studies were
      included in this review, for a total of 15,008 patients. RESULTS: The results
      reported in literature are inconsistent and the impact of surgical and
      oncological therapies is unknown. Intraoperative frozen sections should be
      performed to achieve a negative margin with intraoperative re-excision.
      CONCLUSION: A surgical re-excision of an R1 resection should be considered for
      patients with fewer than three disease-positive nodes because survival is more
      likely to be governed by positive margins than by nodal status.

PMID- 25368227
TI  - Bacteria: prospective savior in battle against cancer.
AB  - Conventional anticancer therapies such as chemotherapy are losing their sheen in
      the battle against cancer. Therefore, strategies for treatment of cancer need to
      be constantly modified to fulfill the growing demands of alternative therapies.
      Several viral and non-viral vectors have been exploited for anticancer gene
      therapy. But over the years bacteria have been proven to be an important
      candidate for successful evasion of cancer. They serve as invaluable source of
      tumor-specific anticancer genes, toxins, polysaccharides for synthesis of
      nanodrugs and gene-delivery vectors. The current review assesses the role of
      important bacterial groups in different spheres of anti-cancer research. 

PMID- 25368228
TI  - Effect of radiation on cell proliferation and tumor hypoxia in HPV-positive head
      and neck cancer in vivo models.
AB  - BACKGROUND/AIM: Human papilloma virus-associated head and neck squamous cell
      carcinomas (HNSCC) represent a distinct subgroup of HNSCC characterized by a
      favorable prognosis and a distinct molecular biology. There is a range of
      unresolved questions regarding the different biology and clinical outcome of HPV
      positive HNSCC. The purpose of the present project was to obtain insight into the
      biology of treatment responsiveness of HPV-related HNSCC. MATERIALS AND METHODS:
      Tumor xenografts were established from HPV-negative (FaDuDD,) and HPV-positive
      (UD2 and UMSCC47) HNSCC cell lines. Tumors were treated with 10 Gy or 20 Gy and
      the effect on the tumor microenvironment was studied at different time points
      after treatment. Cryosections were imaged for cell proliferation, hypoxia, vessel
      density and vessel perfusion. RESULTS: In the HPV-positive tumor models the
      levels of cell proliferation decreased significantly following irradiation. This
      was not seen in the HPV-negative model (FaDuDD). Furthermore, it was found that
      the tumor hypoxic fraction decreased over time after treatment in irradiated HPV
      positive tumors and not in the HPV-negative tumors. CONCLUSION: The
      radiosensitivity previously observed in vitro could be applied in vivo in respect
      to a radiation-induced decrease in proliferating cells. A decreasing hypoxic
      fraction following irradiation in the HPV-positive tumors could explain the lack
      of benefit from hypoxic modifiers observed in patients.

PMID- 25368229
TI  - Blue light activates phase 2 response proteins and slows growth of a431
      epidermoid carcinoma xenografts.
AB  - BACKGROUND: Recent studies suggest that light in the UVA range (320-400 nm)
      activates signaling pathways that are anti-inflammatory, antioxidative and play a
      critical role in protection against cancer. These effects have been attributed to
      NF-E2-related factor (NRF2)-mediated up-regulation of 'phase 2' genes that
      neutralize oxidative stress and metabolize electrophiles. We had previously shown
      that small doses of blue light (400-500 nm) had selective toxicity for cultured
      oral tumor cells and increased levels of peroxiredoxin phase 2 proteins, which
      led to our hypothesis that blue light activates NRF2 signaling. MATERIALS AND
      METHODS: A431 epidermoid carcinoma cells were treated in culture and as nude
      mouse xenografts with doses of blue light. Cell lysates and tumor samples were
      tested for NRF2 activation, and for markers of proliferation and oxidative
      stress. RESULTS: Blue light activated the phase 2 response in cultured A431 cells
      and reduced their viability dose dependently. Light treatment of tumors reduced
      tumor growth, and levels of proliferating cell nuclear antigen (PCNA), and
      oxidized proteins. DISCUSSION: Cellular responses to these light energies are
      worth further study and may provide therapeutic interventions for inflammation
      and cancer.

PMID- 25368230
TI  - Cancer resistance as an acquired and inheritable trait.
AB  - AIM: To induce cancer resistance in wild-type mice and detect if the resistance
      could be inherited to the progeny of the induced resistant mice. Furthermore to
      investigate the spectrum and immunology of this inherited cancer resistance.
      MATERIALS AND METHODS: Resistance to with live S180 cancer cells in BALB/c mice
      was induced by immunization with inactivated S180 cancer cells. The immunization
      was performed by either frozen/thawed or irradiated cancer cells or cell-free
      ascitic fluid (CFAF). RESULTS: In all instances the induced resistance was
      demonstrated to be inheritable. The phenotype was named HICR (heritable induced
      cancer resistance) and was defined as primary resistant progeny from mice
      immunized with frozen/thawed or irradiated S180 cells or CFAF obtained from mice
      with S180 induced ascites. Notably, this resistance was transferred from both
      male and female mice to the offspring of the immunized mice for at least two
      generations. Although inheritable, the frequency of cancer-resistant pups was
      lost over a few generations. Cells from the J774A.1 and RAW cancer cell lines did
      not induce inheritable cancer resistance, and C57BL/6 mice could not pass on
      cancer resistance fluorescence-activated cell sorting (FACS) analyses of the
      peritoneal cells revealed an increased fraction of macrophages. In necropsies of
      resistant mice no histological signs of cancer or other disease was found.
      CONCLUSION: Only materials derived from S180 cells could give rise to HICR mice.
      The molecular basis of the resistance is unknown but may involve epigenetic
      mechanisms. Other examples of inheritability of acquired phenotypic changes exist
      but, to our knowledge, this is the first demonstration of acquired, inherited
      cancer resistance.

PMID- 25368231
TI  - Effect of Withania somnifera root extract on spontaneous estrogen receptor
      negative mammary cancer in MMTV/Neu mice.
AB  - The cancer-preventive activity of an extract of Withania somnifera (WS) roots was
      examined in female transgenic (MMTV/Neu) mice that received a diet containing the
      extract (750 mg/kg of diet) for 10 months. Mice in the treated group (n=35) had
      an average of 1.66 mammary carcinomas, and mice in the control group (n=33) had
      2.48, showing a reduction of 33%. The average weights of the carcinomas were 2.36
      g for mice in the treated group and 2.63 g for the controls, a difference of 10%.
      Labeling indices for Ki67 and proliferating cell nuclear antigen marker in
      mammary carcinomas of the treated group were 35% and 30% lower, respectively,
      than those of the corresponding control group. Expression of the chemokine was
      reduced by 50%. These results indicate that the root extract reduced the number
      of mammary carcinomas that developed and reduced the rate of cell division in the
      carcinomas. 

PMID- 25368232
TI  - Magnolol affects expression of IGF-1 and associated binding proteins in human
      prostate cancer cells in vitro.
AB  - BACKGROUND/AIM: This study investigated the effects of magnolol, a compound from
      Magnolia officinalis, on the behavior of LNCaP and PC3 human prostate cancer
      cells in vitro. MATERIALS AND METHODS: In vitro cell culture approach with
      biochemical tests and Western blot analyses was used. RESULTS: Magnolol, (80 MUM,
      6 hour exposure) was found to affect the expression of insulin-like growth factor
      1 (IGF-1) and associated proteins. In both cell lines, protein expression of IGF
      1 and insulin-like growth factor binding protein-5 (IGFBP-5) were significantly
      decreased, while protein expression of IGFBP-3 was significantly increased.
      Additionally, protein expression of insulin-like growth factor-1 receptor (IGF
      1R) was significantly increased and the phosphorylated form of IGF-1 (p-IGF-1R)
      was significantly decreased in PC3 cells, while IGFBP-4 protein expression was
      significantly increased in LNCaP cells. CONCLUSION: This study has demonstrated
      for the first time that magnolol can alter the expression of IGF-1 and associated
      proteins in human prostate cancer cells in vitro and suggests that magnolol may
      have a potential role as a novel anti-prostate cancer agent.

PMID- 25368233
TI  - Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes
      in colon cancer stem cells.
AB  - Backround: Most solid cancers including colon cancer are believed to be initiated
      from and maintained by cancer stem cells (CSCs), that are responsible for
      treatment resistance, resulting in tumor relapse. The aim of this study was to
      clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the
      regulation of cancer stem cells. MATERIALS AND METHODS: The HCT-116 cell line was
      cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in
      serum-free non-adherent culture. Gene expressions were analyzed by quantitative
      real-time polymerase chain reaction (qRT-PCR) from cells treated with and without
      cyclopamine. RESULTS: HCT-116 sphere-derived cells grown in serum-free, non
      adherent culture, showed significantly increased expression of stem cell markers,
      Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared
      to parental cells grown in conventional culture. The expression of stemness
      markers, Shh downstream genes and EMT markers were higher in cancer spheres than
      the parental cell line and down-regulated by cyclopamine treatment in a dose
      dependent manner. CONCLUSION: Overall, these findings show that cyclopamine
      treatment could down-regulate the expression of stemness markers, shh downstream
      genes and EMT markers on HCT-116 spheres.

PMID- 25368234
TI  - Transcriptional targeting of human liver carboxylesterase (hCE1m6) and
      simultaneous expression of anti-BCRP shRNA enhances sensitivity of breast cancer
      cells to CPT-11.
AB  - BACKGROUND: The major factor limiting the efficacy of breast cancer chemotherapy
      is multidrug resistance due to overexpression of the breast cancer resistance
      protein ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2). We
      hypothesized that conversion of camptothecin-11 (CPT-11) to its highly cytotoxic
      metabolite SN-38 by a mutant human carboxyl esterase (hCE1m6) specifically in
      cancer cells and inhibition of ABCG2 by anti-ABCG2 short hairpin RNA, leads to
      accumulation of a higher concentration of SN-38, resulting in higher therapeutic
      efficacy and less toxicity to normal cells. MATERIALS AND METHODS: A mutant human
      carboxyl esterase hCE1m6 with human telomerase reverse transcriptase promoter was
      integrated into the VISA (VP16-Gal4-WPRE) amplification system. The plasmid was
      transfected into MCF-12A, MDA-MB-231, and MCF-7 cells using JetPRIME(r). Cancer
      specific expression of hCE1m6 in breast cancer cell lines was tested by real-time
      polymerase chain reaction (real time-PCR) and western blot. In vitro conversion
      of CPT-11 to SN-38 was evaluated on lysates of transfected cells. Cytotoxicity of
      CPT-11 against cells transfected with the plasmid was evaluated by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Real
      time PCR and western blot analysis revealed that hCE1m6 was expressed only in
      breast cancer cells, MCF-7 and MDA-MB-231, but not in the normal MCF-12A breast
      cell line. From the CPT-11 conversion assay on cell lysates, it was found that
      expressed hCE1m6 in cancer cells was able to effectively convert CPT-11 to SN-38.
      CONCLUSION: Breast cancer cell lines transfected with hCE1m6 showed an increased
      susceptibility to CPT-11 in comparison to MCF-12A cells.

PMID- 25368235
TI  - Immunogenic modulation of cholangiocarcinoma cells by chemoimmunotherapy.
AB  - BACKGROUND/AIM: Chemoimmunotherapy has been used to treat intrahepatic
      cholangiocarcinoma (ICC). However, little is known about the phenomena underlying
      the immunomodulation of ICC cells elicited by chemoimmunotherapy. MATERIALS AND
      METHODS: Primary ICC cells from a patient with ICC who received gemcitabine
      followed by 5-fluorouracil (5-FU), both combined with dendritic cells pulsed with
      Wilms' tumor 1 (WT1) peptides were cultured. ICC cells were treated with
      gemcitabine, 5-FU or interferon (IFN)-gamma in vitro. The phenotype of the ICC
      cells was examined by flow cytometry and quantitative reverse transcription
      polymerase chain reaction. RESULTS: Stimulation of the ICC cells with gemcitabine
      resulted in up-regulation of WT1 mRNA, programmed death receptor ligand-1 (PDL1)
      and calreticulin. Gemcitabine, 5-FU and IFN-gamma induced up-regulation of mucin
      1. Moreover, human leukocyte antigen (HLA)-ABC, HLA-DR and PDL1 were extremely up
      regulated by IFN-gamma. CONCLUSION: Chemoimmunomodulating agents alter the
      immunogenicity of ICC cells, resulting in complex clinical efficacy results.

PMID- 25368236
TI  - Differential impact of tumor-infiltrating immune cells on basal and luminal
      cells: implications for tumor invasion and metastasis.
AB  - BACKGROUND/AIM: Regarding the impact of tumor-infiltrating immune cells on tumor
      cells, many contradictory reports have been published. We have hypothesized that
      these controversies result from differences in tissue types and tumor stages, in
      which immune cells are variably distributed and differentially associated with
      epithelial cells. Our current study compared the pattern and frequency of
      physical association of tumor-infiltrating immune cells with different
      parenchymal cells of human breast and prostate tumors harboring normal,
      hyperplastic, in situ, and invasive components. MATERIALS AND METHODS: The
      cytological, biological, and molecular alterations were assessed with double
      immunohistochemistry, double fluorescent labeling, apoptosis assay, and gene
      expression profiling. RESULTS: Our study detected several previously undescribed
      features: (i) over 95% of infiltrating immune cells were seen within normal,
      hyperplastic, or in situ cancer structures with focally-disrupted capsules, and
      fewer than 5% were found within invasive cancer; (ii) over 95% of normal,
      hyperplastic, and in situ cancerous epithelial cells were physically shielded
      from immune cells by the surrounding myoepithelial or basal cell layer; (iii)
      about 90% of myoepithelial or basal cells physically associated with immune cells
      and such residual cells within focally disrupted layers exhibited distinct
      degeneration, including apoptosis, necrosis, and reduced expression of tumor
      suppressor p63; (iv) epithelial cells overlying focally disrupted tumor capsules
      surrounded by immune cells had substantially higher proliferation than their
      adjacent counterparts, and some of the proliferating cells were arranged as
      tongue-like projections invading the stroma; and (v) microdissected cells
      overlying focally disrupted tumor capsules had more than 5-fold higher expression
      of stem cell lineage markers KIT and NCOR2. CONCLUSION: Tumor-infiltrating immune
      cells are primarily associated with degenerated myoepithelial or basal cells
      causing focal disruptions of the capsule, which selectively favor proliferation,
      invasion, and dissemination of the overlying tumor stem cells.

PMID- 25368237
TI  - Angiogenesis in potentially malignant lesions and carcinomas during experimental
      oral carcinogenesis: a preliminary study in the hamster cheek pouch.
AB  - AIM: To evaluate vascular morphology and density, angiogenic switch activation,
      vascular endothelial growth factor (VEGF) expression, and endothelial cell (EC)
      proliferation in the hamster cheek pouch (HCP) model of oral cancer. MATERIALS
      AND METHODS: Immunohistochemical detection of factor VIII, 5'-Bromo-2'
      Deoxyuridine (BrdU) and VEGF was performed in pre-malignant and tumoral tissues.
      RESULTS: Activation of angiogenesis was detected adjacent to epithelial
      dysplasia. Vascularized area and perimeter (p<0.001) increased in dysplasias and
      tumors. Tumor blood vessels exhibited an enhanced vascular compression (p<0.001)
      and structural alterations. EC proliferation was similar in dysplasias and
      carcinomas. An increase in vascular density, EC proliferation and VEGF expression
      was found in potentially malignant tissues but not in carcinomas. CONCLUSION: The
      angiogenic switch occurs in the dysplastic stage preceding tumor development in
      the HCP model of oral cancer. In potentially malignant tissues, increased VEGF
      expression favors EC proliferation and an increase in vascular density.
      Conversely, in tumors, VEGF is no longer of pivotal importance.

PMID- 25368238
TI  - Human telomerase reverse transcriptase is a promising target for cancer
      inhibition in squamous cell carcinomas.
AB  - BACKGROUND/AIM: The present study aimed to investigate whether the down
      regulation of human telomerase reverse transcriptase (hTERT) may induce an anti
      invasive effect in oral squamous cell cancer cell lines. MATERIALS AND METHODS: A
      genetically-engineered squamous carcinoma cell line overexpressing hTERT in
      immortalized oral keratinocytes transfected by human papilloma virus (HPV)-16
      E6/E7 (IHOK) was used. In vivo tumorigenicity was examined using an orthotopic
      xenograft model of nude mice. For evaluating anti-invasive activity by knockdown
      of hTERT expression, transwell invasion assay and real-time polymerase chain
      reaction (PCR) for matrix metalloproteinases (MMP) were employed. RESULTS: The
      down-regulation of hTERT expression reduced the invasive activity and MMP
      expression. This result was re-confirmed in the HSC3 oral squamous carcinoma cell
      line. CONCLUSION: Targeting hTERT may lead to novel therapeutic approaches.

PMID- 25368239
TI  - Nuclear expression of chemokine receptor CXCR4 indicates poorer prognosis in
      gastric cancer.
AB  - BACKGROUND: The CXCL12/CXCR4 axis plays a pivotal role in cancer progression and
      metastases in various epithelial cancer cells. The aim of the present study was
      to evaluate the localization and correlation between CXCL12/CXCR4 expression and
      clinicopathological features in gastric cancers. MATERIALS AND METHODS: This
      study included 111 Japanese patients with primary gastric cancers, which invade
      submucosa or more, all of whom underwent gastrectomy between 1992 and 1996.
      Immunohistochemical analysis was performed. RESULTS: A significant correlation
      was found in the immunoreactivity of nuclear CXCR4 and poor differentiation
      (p=0.0026), infiltrated pattern (p<0.0001), larger size (p<0.0001), advanced
      stage (p=0.0342) and reduced 5-year survival rate (30% vs. 61%, p=0.0012).
      Multivariate analysis revealed that high nuclear CXCR4 immunoreactivity (RR:
      3.077, p=0.0329) retained its strength as an independent prognostic factor for
      overall survival. CONCLUSION: High immunoreactivity of nuclear CXCR4 in gastric
      cancer suggests that CXCL12 binds to its unique receptor CXCR4 at the membrane,
      translocates to the nucleus and then becomes more invasive, and thus can be
      considered a prognostic factor.

PMID- 25368240
TI  - High-density array comparative genomic hybridization detects novel copy number
      alterations in gastric adenocarcinoma.
AB  - AIM: To investigate frequent quantitative alterations of intestinal-type gastric
      adenocarcinoma. MATERIALS AND METHODS: We analyzed genome-wide DNA copy numbers
      of 22 samples and using CytoScan(r) HD Array. RESULTS: We identified 22 gene
      alterations that to the best of our knowledge have not been described for gastric
      cancer, including of v-erb-b2 avian erythroblastic leukemia viral oncogene
      homolog 4 (ERBB4), SRY (sex determining region Y)-box 6 (SOX6), regulator of
      telomere elongation helicase 1 (RTEL1) and UDP-Gal:betaGlcNAc beta 1,4-
      galactosyltransferase, polypeptide 5 (B4GALT5). The most significant alterations
      related to peritoneal invasion involved the regions 13q21.1 (gain) and 15q15.1,
      17q23.1, 19q13.2 and 20q11.22 (loss of heterozygozity; LOH), where we found LOH
      of erythrocyte membrane protein band 4.1-like 1 (EPB41L1) gene. In relation to
      early age of onset, the most significant alterations were gains in the regions
      Xq26 and Xp22.31 and a loss in the region 11p15.4. CONCLUSION: These quantitative
      changes may play a role in the development of this type of neoplasia and may be
      used as markers in evaluating poor prognosis, as well as act as potential
      therapeutic targets for gastric cancer.

PMID- 25368241
TI  - Sorafenib induces ferroptosis in human cancer cell lines originating from
      different solid tumors.
AB  - BACKGROUND/AIM: Ferroptosis is a recently identified form of regulated necrosis
      that can be experimentally induced in cancer cells with the chemical inducer
      erastin. Recently, we identified sorafenib, an inhibitor of oncogenic kinases, as
      an inducer of ferroptosis in hepatocellular carcinoma cells. Whether sorafenib is
      able to exert its ferroptotic activity in cancer cells originating from other
      tissues is presently unclear. MATERIALS AND METHODS: We compared the levels of
      ferroptosis induced by sorafenib with those induced by the reference compound
      erastin in a panel of ten human cell lines originating from various tissues.
      RESULTS: Sorafenib induced ferroptosis in different cancer cell lines. We found a
      positive correlation between the ferroptotic potency of sorafenib and erastin.
      Compared to other kinase inhibitors, sorafenib is the only drug that displays
      ferroptotic efficacy. CONCLUSION: The findings establish sorafenib as the first
      clinically-approved anticancer drug that can induce ferroptosis.

PMID- 25368242
TI  - BH3 mimetics inhibit growth of chondrosarcoma--a novel targeted-therapy for
      candidate models.
AB  - BACKGROUND: Chondrosarcoma is refractory to conventional chemotherapy. BH-3
      mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti
      apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical
      role in survival of chondrosarcoma cells. MATERIALS AND METHODS: Chondrosarcoma
      cell lines SW-1353 and CS-1 were used as the disease model. We used
      immunoblotting to assess the expression of target molecules Bcl2 and Bcl-xL, and
      the apoptotic inducers Bcl2-associated X (Bax) and Bcl2-antagonist/killer (Bak).
      In vitro growth inhibition by BH-3 mimetics was confirmed by photomicroscopic
      cell counting and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Apoptotic induction was
      confirmed by Enzyme-Linked ImmunoSorbent Assay (ELISA). In vivo growth inhibition
      was assessed in a non-obese diabetic/severe combined immunodeficient (NOD/SCID)
      mouse model. RESULTS: Expression of the target and effector molecules was
      confirmed in chondrosarcoma cell lines. BH3 mimetics significantly inhibited cell
      growth and induced apoptosis in vitro. Administration of ABT-263 inhibited
      chondrosarcoma growth and improved survival in a mouse model. CONCLUSION: BH3
      mimetics represent a novel treatment modality for chondrosarcoma.

PMID- 25368243
TI  - Indoleamine-2,3-dioxygenase in an immunotherapy model for Ewing sarcoma.
AB  - BACKGROUND/AIM: Interleukin-2 (IL2) transgenic Ewing sarcoma cells reduce tumor
      growth in vivo and in vitro. In the present study we analyzed the expression of
      immune suppressive indoleamine-2,3-dioxygenase (IDO) in this model. MATERIALS AND
      METHODS: Expression of IDO was analyzed by polymerase chain reaction. The impact
      of the cluster of differentiation 137 (CD137)/CD137 ligand (CD137L) co
      stimulatory system on expression of IDO and different cytokines was analyzed both
      in vivo and in vitro. RESULTS: Tumors that developed in vivo in the presence of
      IL2 transgenic tumor cells expressed IDO. The presence of CD137L transgenic tumor
      cells led to down-regulation of IDO. Further in-vitro analysis of this phenomenon
      indicated that IDO was expressed in tumor cells as a consequence of interferon
      gamma produced by lymphocytes in response to IL2. Depending on the concentration
      of IL2, stimulation of CD137 increased or reduced cytokine production in
      lymphocytes. CONCLUSION: Our data indicate that the CD137/CD137L pathway can
      modulate the immune response against Ewing sarcoma cells.

PMID- 25368244
TI  - Surrounding cells affect the gene expression pattern of human beta-defensins in
      squamous cell carcinoma in vitro.
AB  - BACKGROUND/AIM: Defensins are basic peptides involved in non-immune bio-defense
      mechanisms in a normal epithelium. Human oral squamous cell carcinoma cells
      (OSCC) also produce human beta-defensins (HBDs), although their exact function is
      not clear. This study aimed to analyze the variation in gene expression levels of
      hBDs in co-cultures of OSCC with murine cells. MATERIALS AND METHODS: Two OSCC
      cell lines (HSC-3, HSC-4) were co-cultured with mouse embryonic fibroblasts,
      NIH/3T3 or a mouse chondrogenic cell line derived from teratocarcinoma, ATDC5,
      for 1.5 days. Expression patterns of the hBD genes were investigated by real-time
      polymerase chain reaction (RT-PCR). RESULTS: hBD1 expression increased when co
      cultured with NIH/3T3 but decreased when co-cultured with ATDC5. Expression of
      hBD2 and hBD4 tended to decrease. OSCC cells formed colonies when co-cultured
      with NIH/3T3 but were scattered when co-cultured with ATDC5. CONCLUSION: hBDs
      expression in OSCC is dependent on the type of co-cultured cells and differences
      in gene expression may be responsible for the morphological differences observed.
      OSCC may produce HBDs for purposes other than bio-defense by surrounding cells.

PMID- 25368245
TI  - The combination of nuclear factor kappa B, cyclo-oxygenase-2 and vascular
      endothelial growth factor expression predicts poor prognosis in stage II and III
      colorectal cancer.
AB  - BACKGROUND/AIM: To evaluate immunohistochemical expression of nuclear factor
      kappa B (NFkappaB), cyclo-oxygenase (COX)-2, and vascular endothelial growth
      factor (VEGF) and the impacts thereof on clinicopathological tumor features and
      survival in patients with colorectal cancer. MATERIALS AND METHODS: Sixty-six
      patients with colorectal cancer (stage II or III) were enrolled. RESULTS: The
      positive expression rates of NF-kappaB, COX2, and VEGF were 62.1%, 51.5%, and
      63.6%, respectively. Sixteen tumor samples (24.2%) coexpressed all three markers.
      Coexpression of all three markers correlated with pTNM III, poor histological
      grade, larger tumor diameter, and elevated carcinoembryonic antigen level. pTNM
      III and coexpression of all three markers were independent prognostic factors for
      cancer-specific and disease-free survival. CONCLUSION: The combination of
      NFkappaB, COX2, and VEGF expression correlated with advanced pathological
      features and had a prognostic impact on cancer-specific and disease-free
      survival. These findings suggest that coexpression of three markers may have a
      synergistic effect on aggressive tumor biology.

PMID- 25368246
TI  - HDAC inhibitor-loaded bone cement for advanced local treatment of osteosarcoma
      and chondrosarcoma.
AB  - The treatment of osteosarcoma, especially wide resection, is challenging. An
      additional local drug therapy after resection using anti-neoplastic bone cement
      (Polymethylmethacrylate (PMMA)) could help improve the outcome of therapy. In
      this study, we evaluated the effects of PMMA loaded with valproic acid (VPA) and
      suberoylanilide hydroxamic acid (SAHA) on the cell activity of a SaOs-2 cell
      culture, as well as the elution rate of the drugs out of the bone cement.
      MATERIALS AND METHODS: In our experiments, we used the SaOs-2 osteosarcoma and
      the SW1353 chondrosarcoma cell line. Bone cement clots (5 g) were prepared and
      loaded with different drug concentrations of VPA (25 mg and 50 mg) and SAHA (1
      mg, 2.5 mg and 5 mg). Two control groups were established, one with a native
      cement clot, the other with human mesenchymal stem cells, in order to evaluate
      toxicity on non tumor-cells. Cell activity was measured using an Alamar Blue
      assay on days 1, 2, 3, 4 and 7. The cement clots were additionally examined in a
      material testing unit for biomechanical and structural changes. RESULTS: Tumor
      cells showed a significant and complete reduction of activity under therapy with
      VPA and SAHA. Drug release of VPA was extensive between days 0 and 3 and
      decreased progressively to day 7. Cumulative drug concentration in the medium
      continuously increased. Biomechanical testing of the cement clots showed no
      differences in stability and architecture compared to the control group. SaOs-2
      and SW1353 cells with medium from native cement clots without drug therapy
      presented a cell activity of 100% in all groups and during all measurements.
      Human mesenchymal stem cells were not significantly affected during therapy with
      VPA and low concentrations of SAHA. In contrast, cell activity of human
      mesenchymal stem cells was significantly reduced under therapy with higher
      concentrations of SAHA, with an approximately linear decrease between days 0-3
      and a rapidly decreasing activity between days 4-7. CONCLUSION: A local cytotoxic
      therapy in the treatment of osteosarcoma and chondrosarcoma might improve the
      rate of metastasis and survival of patients. Our results present an encouraging
      approach to loading PMMA with anti-neoplastic drugs.

PMID- 25368247
TI  - Antitumor activity of acriflavine in lung adenocarcinoma cell line A549.
AB  - Aim/Materials and Methods: In order to develop better drugs against non-small
      cell lung cancer (NSCLC), we screened a variety of compounds and treated the
      human lung adenocarcinoma cell line A549 with different drug concentrations. We
      then examined the cell viability using the MTT assay. RESULTS: Data show that a
      new candidate drug, acriflavine (ACF), suppresses the viability of A549 cells in
      a concentration- and time-dependent manner. Flow cytometry analysis revealed that
      ACF significantly caused cell growth arrest in the G2/M phase on A549 cells.
      Moreover, ACF decreased Bcl-2 expression and increased Bax expression. The
      content of cleaved poly(ADP-ribose)polymerase-1 (PARP-1) and caspase-3 are
      significantly increased. These findings suggest that ACF is cytotoxic against
      A549 cells and suppresses A549 cells growth through the caspase-3 activation
      pathway. In the in vivo test, nude mice bearing A549 cells xenografts by
      intravenous injection were randomly assigned into two groups: control and
      experimental group. Treatment was initiated 10 days after implantation and
      intraperitoneal injection of 0.9% normal saline or 2 mg/kg of ACF was continued
      daily for five weeks. ACF treatment significantly decreased tumor size and tumor
      spots on lung surface of tumor-bearing mice. CONCLUSION: ACF can inhibit cell
      growth in A549 cells. Our results may assist on the delineation of the
      mechanism(s) leading to NSCLC cell growth inhibition and provide a new antitumor
      strategy against NSCLC.

PMID- 25368248
TI  - Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of
      cancer cells.
AB  - BACKGROUND: The aim of the present study was to determine the effects of osthole
      on cell proliferation and viability, cell-cycle progression and induction of
      apoptosis in human laryngeal cancer RK33 and human medulloblastoma TE671 cell
      lines. MATERIALS AND METHODS: Cell viability was measured by means of the MTT
      method and cell proliferation by the 5-bromo-2-deoxyuridine (BrdU) incorporation
      assay. Cell-cycle progression was determined by flow cytometry, and induction of
      apoptosis by release of oligonucleosomes to the cytosol. The gene expression was
      estimated by a quantitative polymerase chain reaction (qPCR) method. High
      performance counter-current chromatography (HPCCC) was applied for isolation of
      osthole from fruits of Mutellina purpurea. RESULTS: Osthole decreased
      proliferation and cell viability of cancer cells in a dose-dependent manner. The
      tested compound induced apoptosis, increased the cell numbers in G1 and decreased
      cell number in S/G2 phases of the cell cycle, differentially regulating CDKN1A
      and TP53 gene expression depending on cancer cell type. CONCLUSION: Osthole could
      be considered as a potential compound for cancer therapy and chemoprevention.

PMID- 25368249
TI  - Involvement of reactive oxygen species in the enhancement of membrane lipid
      peroxidation by sonodynamic therapy with functionalized fullerenes.
AB  - BACKGROUND/AIM: Sonodynamic cancer therapy is based on the preferential uptake
      and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and
      subsequent activation of the drug by ultrasound irradiation. In the present
      study, we investigated the participation of lipid peroxidation in the mechanism
      of the sonodynamically-induced antitumor effect with functionalized fullerenes,
      such as polyhydroxy fullerene (PHF. MATERIALS AND METHODS: Ultrasonically-induced
      cell damage and lipid peroxidation with PHF were compared in the same in vitro
      insonation setup. Sarcoma 180 cells suspended in PBS were exposed to 2 MHz
      ultrasound in the presence and absence of PHF. Cell viability was determined by
      the Trypan Blue exclusion test. Lipid peroxidation in cell membranes was
      estimated by measuring the amount of malondialdehyde as the thiobarbituric acid
      reactive-substances. RESULTS: Significant enhancement of the rates of both
      ultrasonically-induced cell damage and lipid peroxidation was observed in the
      presence of PHF, both of which were positively correlated with PHF. The
      enhancement of cell damage and lipid peroxidation with PHF was suppressed by
      reactive oxygen scavengers such as histidine and tryptophan. CONCLUSION: The good
      correlation observed in the presence of PHF suggests that membrane lipid
      peroxidation is one of the important intermediary events in sonodynamically
      induced cellular damage. The inhibitory effects of histidine and tryptophan also
      provide evidence that singlet oxygen plays an important role in PHF-mediated
      sonosensitization of membranes and that this moiety may be an important mediator
      of cell destruction in sonodynamic therapy associated with PHF and ultrasound.

PMID- 25368250
TI  - Effects of arsenic compounds on growth, cell-cycle distribution and apoptosis of
      tretinoin-resistant human promyelocytic leukemia cells.
AB  - BACKGROUND/AIM: The effects of inorganic and organic arsenicals on proliferation,
      cell-cycle distribution, and apoptosis of all-transretinoic acid (ATRA)-resistant
      human promyelocytic leukemia HL-60 (HL-60-R2) cells were herein investigated.
      MATERIALS AND METHODS: Cell proliferation was examined by 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide assay. Cell-cycle distribution and
      apoptotic cells were analyzed by flow cytometry. RESULTS: The 50% inhibitory
      concentrations (IC50 values) for As2O3 against proliferation of HL-60 and HL-60
      R2 cells were 12.2 and 7.2 MUM, while those for arsenate were >200 and 62.1 MUM,
      respectively. In contrast, organic methylarsinic acid, dimethylarsonic acid,
      trimethylarsine oxide, and tetramethylarsonium did not exert any inhibitory
      effects even at 200 MUM. As2O3 and arsenate increased the proportion of apoptotic
      cells dose-dependently at a concentration range of 5-200 MUM. As2O3 did not
      activate caspase 3/7 in HL-60 and HL-60-R2 cells. CONCLUSION: As2O3 and arsenate
      inhibit cell proliferation, affect cell-cycle distribution, and induce apoptosis
      of ATRA-resistant HL-60-R2 cells. The apoptosis-inducing mechanism appears not to
      be mediated through caspase3/7.

PMID- 25368251
TI  - Protein and mRNA expression of notch pathway components in operable tumors of
      patients with laryngeal cancer.
AB  - BACKGROUND: There exist substantial evidence that laryngeal cancer represents a
      unique entity among squamous head and neck carcinomas. MATERIALS AND METHODS:
      Tumors from 289 patients with squamous cell laryngeal cancer were assessed for
      protein (immunohistochemistry) and mRNA (qRT-PCR) expression of Notch pathway
      components (Notch1 to 4 receptors and Jagged1 ligand) on tissue microarrays.
      RESULTS: In univariate analysis, enhanced nuclear Jagged1 expression conferred a
      longer disease-free survival (DFS) (p=0.013) and overall survival (OS) (p=0.004),
      in contrast to the unfavorable prognostic value of Notch3 for both DFS (p=0.009)
      and OS (p=0.024). In multivariate analysis, overexpression of either Notch or
      cytoplasmic Jagged1 conferred an unfavorable effect on DFS (Hazard Ratio=1.88,
      95% Confidence Interval=1.03-3.43, p=0.04). CONCLUSION: Our study indicates a
      consistent unfavorable effect of Notch3 and cytoplasmic Jagged1 protein
      expression, a favorable impact of nuclear Jagged 1 localization, and a
      differential prognostic value of Notch2 expression according to the presence of
      cytoplasmic Jagged 1.

PMID- 25368253
TI  - Reduced expression of growth and differentiation factor-9 (GDF9) is associated
      with aggressive behaviour of human clear-cell renal cell carcinoma and poor
      patient survival.
AB  - BACKGROUND: Growth and differentiation factor-9 (GDF9) is a member of the bone
      morphogentic protein (BMP) family. GDF9 was recently shown to be a regulator of
      the development and spread of cancer cells, including kidney cancer cells.
      However, the clinical implication of GDF9 in human clear-cell renal cell
      carcinoma (CCRCC) remains unknown. In the present study, the expression of GDF9
      in human CCRCC tissues, and correlation between GDF9 and pathological grade and
      stage of the tumours were examined in CRCC specimens. MATERIALS AND METHODS: The
      expression of GDF9 was examined in paired human normal renal and CCRCC tumour
      tissues (n=86). The expression of GDF9 in human renal tissues was assessed at
      both the mRNA and protein levels using reverse transcription-polymerase chain
      reaction and western blot. Furthermore, the survival curve was constructed using
      Kaplan-Meier method. RESULTS: Decreased GDF9 protein levels were seen in CCRCC
      tissues compared with normal tissues. Low protein levels were seen in tumours
      with high clinical stages and with high pathological nuclear grade of CCRCC.
      Likewise, levels of GDF9 transcript in normal renal specimens was significantly
      higher than that in CCRCC tissues. The transcript levels of GDF9 differed
      significantly amongst different clinical stages and different pathological
      nuclear grade of CCRCC: The higher the clinical stage or pathological nuclear
      grade of CCRCC, the lower the transcript level of GDF9. Cumulative survival
      curves indicated that GDF9 mRNA expression was negatively correlated with
      cumulative survival time. Patients with high level of GDF9 had significantly
      longer survival time than the patients with low level of GDF9 (p<0.001).
      CONCLUSION: GDF9 expression is markedly decreased in CCRCC, and is linked to
      pathological grade, clinical stage and long-term survival of the patients. This
      suggests that GDF9 is a potential tumour suppressor in CCRCC.

PMID- 25368254
TI  - N-(2-amino-5-chlorobenzoyl)benzamidoxime derivatives inhibit human leukemia cell
      growth.
AB  - BACKGROUND/AIM: Amidoxime derivatives have been previously reported to have
      potent anti-microbial and anti-tumor activity. Little is known about the tumor
      cell growth-inhibition mechanism of amidoximes, especially benzamidoxime
      derivatives. Herein we determined the effects of N-(2-amino-5
      chlorobenzoyl)benzamidoxime analogs on mammalian cancer cells. MATERIALS AND
      METHODS: We synthesized four chloride-substituted benzamidoxime analogs from the
      original benzamidoxime to investigate their anticancer cell activity using the
      Jurkat T-cell lymphoma cell line and the human leukemia cell line HL-60RG.
      RESULTS: All amidoxime derivatives inhibited Jurkat and HL-60RG cell viability
      dose-dependently. Benzamidoximes tended to damage HL-60RG cells to a greater
      extent compared to Jurkat cells. Benzamidoximes with chloride substitutes caused
      a strong decrease in cell growth, and this cell growth attenuation was transient
      at 5 MUM (below the half-maximal inhibitory concentration, IC50) but long-lasting
      at 10 MUM (greater than the IC50). CONCLUSION: Benzamidoxime derivatives caused a
      transient cell-cycle delay at a low dose and cell death at a high dose.

PMID- 25368252
TI  - Effect of neoadjuvant chemoradiation on tumor-infiltrating/associated lymphocytes
      in locally advanced rectal cancers.
AB  - BACKGROUND: Lymphocytes and natural killer cells (NK) appear to be important in
      colorectal cancer. Their role in chemoradiotherapy for rectal cancers is unclear.
      We evaluated T-lymphocytes (CD3), sub-groups CD4 and CD8, and NK cells
      (CD56+CD57) in normal and rectal tumor tissues pre- and post-chemoradiotherapy,
      and investigated their relationship to tumor regression grade, disease-free
      survival and pathological stage. MATERIALS AND METHODS: Tissue microarrays from
      colonoscopic biopsies, resection specimens and normal tissues, from 52 patients,
      were immunostained. RESULTS: NK cell counts were significantly lower in tumor
      samples compared to normal tissues (p=0.007). T-lymphocyte counts were higher in
      post-treatment compared to pre-treatment samples (p=0.025), specifically in the
      CD8 subgroup after long-course treatment. The results suggested an association
      between post-treatment CD8 and NK cell counts with higher tumor regression. No
      associations were found with regard to stage or disease-free survival.
      CONCLUSION: NK cell counts were significantly reduced in rectal cancers compared
      to normal tissues, while total T-lymphocyte counts increased post
      chemoradiotherapy. Both appeared important in tumor regression.

PMID- 25368255
TI  - Gefitinib inhibits sodium phosphate co-transporter III isoform 1 in a model of
      human malignant glioma.
AB  - BACKGROUND: The purpose of the present was to investigate whether the in vitro
      effects of gefitinib, an EGFR tyrosine kinase inhibitor, may regulate the
      expression of type III sodium phosphate Na/Pi co-transporters in an in vitro
      glioma model. MATERIALS AND METHODS: Proliferation studies, global native EGFR
      and phosphorylated EGFR expressions, phosphate transporter type III isoform
      1(PiT1) expression and phosphate transport with 99mTc-(V)-DMSA radioligand were
      performed in G111 (grade II astrocytoma), U-87-MG (grade III astrocytoma) and
      G152 (grade IV glioblastoma) cells. RESULTS: Cells treated with gefitinib showed
      a significant decrease in proliferation in relation to EGFR and p-EGFR
      expression. Gefitinib also produced a decrease in phosphate transport mediated
      PIT1 expression at both the RNA and protein levels. CONCLUSION: The link between
      gefitinib acting on the EGFR and PiT1 regulation in these cancer cell lines was
      herein shown.

PMID- 25368256
TI  - Impact of STAT3 inhibition on survival of osteosarcoma cell lines.
AB  - BACKGROUND/AIM: Osteosarcoma is often a fatal malignancy. Constitutive STAT3
      activation is associated with various human cancers and commonly suggests poor
      prognosis. We aimed to investigate the effect and potential molecular mechanisms
      of STAT3 inhibition on osteosarcoma. MATERIALS AND METHODS: STAT3 inhibitor S3I
      201 was investigated in six osteosarcoma cell lines. Crystal violet colorimetric,
      clonogenic, cleaved caspase-3 assays and western blot were performed to measure
      the effect and mechanisms of STAT3 inhibition. RESULTS: All osteosarcoma cell
      lines expressed phosphorylated STAT3. Anti-proliferative effects of S3I-201 were
      dose- and time-dependent. S3I-201 also inhibited colony-formation and induced
      apoptosis through the caspase cleavage pathway. Finally, molecular mechanism
      studies suggested that down-regulation of STAT3 phosphorylation and downstream
      STAT3-target genes such as cyclin D1 and survivin may contribute to S3I-201
      mediated anti-proliferation and apoptosis. CONCLUSION: Inhibition of STAT3
      signalling suppressed osteosarcoma cell growth and induced apoptosis, and
      indicated that STAT3 targeted-therapy may have therapeutic potential in
      osteosarcoma.

PMID- 25368257
TI  - Development and pre-clinical evaluation of new 68Ga-NOTA-folate conjugates for
      PET imaging of folate receptor-positive tumors.
AB  - In an attempt to develop new folate radiotracers with favorable biochemical
      properties for detecting folate receptor-positive cancers, we synthesized 68Ga
      NOTA- and 68Ga-NOTAM-folate conjugates using a straightforward and a one-step
      simple reaction. Radiochemical yields were greater than 95% (decay-corrected)
      with total synthesis time of less than 20 min. Radiochemical purities were always
      greater than 98% without high-performance liquid chromatography (HPLC)
      purification. These synthetic approaches hold considerable promise as a rapid and
      simple method for 68Ga-folate conjugate preparation with high radiochemical yield
      in a short synthesis time. In vitro tests on the KB cell line showed that
      significant amounts of the radioconjugates were associated with cell fractions.
      Biodistribution studies in nude mice bearing human KB xenografts, demonstrated a
      significant tumor uptake and favorable biodistribution profile for 68Ga-NOTA
      folate over the 68Ga-NOTAM-folate conjugate. The uptake in the tumors was blocked
      by excess injection of folic acid, suggesting a receptor-mediated process. These
      results demonstrate that the 68Ga-NOTA-folate conjugate may be useful as a
      molecular probe for detection and staging of folate receptor-positive cancers,
      such as ovarian cancer and their metastasis, as well as monitoring tumor response
      to treatment.

PMID- 25368258
TI  - A B-myb--DREAM complex is not critical to regulate the G2/M genes in HPV
      transformed cell lines.
AB  - BACKGROUND/AIM: It is well-established that HPV E7 proteins, encoded by human
      papillomavirus (HPV) genes, frequently associated with cervical cancers bind
      avidly to the retinoblastoma (RB) family of pocket proteins and disrupt their
      association with members of the E2F transcription factor family. Our previous
      study showed that the repressive p130-dimerization partner, RB-like, E2F and
      multi-vulval class (DREAM) complex was disrupted by HPV16 E7 proteins in order to
      maintain the viral replication in CaSki cells. However, we would like to address
      whether the activator B-myb-DREAM complex is critical in regulating the
      replication and mitosis phase since our previous study showed increased B-myb
      DREAM expression in HPV-transformed cell lines when compared to control cells.
      RESULTS: The association of B-myb with both LIN-54 and LIN-9 was equally
      decreased by depleting LIN-54 in CaSki cells. Flow cytometry analysis showed that
      LIN-54 depletion caused an increased proportion of G2/M cells in T98G, SiHa and
      CaSki cells. The mRNA levels of certain S/G2 genes such as cyclin B, aurora
      kinase A and Polo-like kinase 1 have demonstrated a marginal increased in CaSki
      Lin-54-depleted cells when compared to SiHa- and T98G-Lin-54-depleted cells. We
      further confirmed this experiment by depleting the B-myb itself in CaSki cells
      and the results showed the same pattern of cell cycle and mRNA levels for S/G2
      genes when compared to LIN-54- and LIN-9-depleted cells. CONCLUSION: The B-myb
      DREAM complex might not be vital for progression through mitosis in cells lacking
      a G1/S checkpoint and not as crucial as the p130-DREAM complex for the survival
      of the HPV virus.

PMID- 25368259
TI  - Sodium valproate, a histone deacetylase inhibitor, enhances the efficacy of
      vinorelbine-cisplatin-based chemoradiation in non-small cell lung cancer cells.
AB  - AIM: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing
      radiation (IR) combination against non-small cell lung cancer (NSCLC) cells by co
      administration of sodium valproate (VPA), a histone deacetylase inhibitor, and to
      elucidate molecular events underpinning treatment efficacy. MATERIALS AND
      METHODS: The NSCLC A549 cell line was treated with cisplatin (0.2 MUg/ml),
      vinorelbine (2 nM), VPA (1 mM) and IR (2.5 Gy) alone, or in combination. Cell
      proliferation, cell-cycle distribution, apoptosis, and levels of DNA double
      strand breaks, activated DNA damage checkpoint kinases pCHK1, pCHK2, cell-cycle
      inhibitors p21CIP1/WAF1 and p27KIP1 were assessed. RESULTS: VPA markedly enhanced
      the DNA-damaging effect of the cisplatin-vinorelbine-IR combination and induced
      increased DSBs, and expression of pCHK2, pCHK1, p21CIP1/WAF1 and p27KIP1. These
      molecular changes led to cell-cycle arrest and increased apoptosis and
      consequently markedly curtailed cancer cell growth. CONCLUSION: VPA markedly
      enhances the anticancer activity of cisplatin-vinorelbine-IR combination. This
      finding has translational implications for enhancing the efficacy of anticancer
      treatment and for reducing side-effects by reducing doses of radiation and drugs.

PMID- 25368260
TI  - Cytotoxic and anti-metastatic activities of phenolic compounds from Dendrobium
      ellipsophyllum.
AB  - BACKGROUND/AIM: Phenolic compounds isolated from Dendrobium ellipsophyllum Tang &
      Wang (Orchidaceae) have been shown to possess potential pharmacological activity;
      however, their anticancer as well as anti-metastasis activities are largely
      unknown. The aim of the present study was to isolate active compounds from D.
      ellipsophyllum and to explore the possible effects of phenolic compounds isolated
      from the plant for cytotoxic as well as anti-metastatic properties. MATERIALS AND
      METHODS: The compounds were isolated by using chromatographic techniques
      including silica gel and Sephadex LH20. Each of the isolates was evaluated for
      their cytotoxicity on H292 human lung cancer cell lines by 2,3-Bis(2-methoxy-4
      nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. The cytotoxic
      compounds were further evaluated for apoptosis-inducing and anoikis-sensitizing
      effects. RESULTS: Ten phenolic compounds were isolated, 5,7-dihydroxy-chromen-4
      one (1:); 4,5-dihydroxy-2,3-dimethoxy-9,10-dihydrophenanthrene (2:); moscatilin
      (3:), 4,4'-dihydroxy-3,5-dimethoxybibenzyl (4:); 4,5,4'-trihydroxy-3,3'
      dimethoxybibenzyl (5:); (2S)-homoeriodictyol (6:); (2S)-eriodictyol (7:);
      chrysoeriol (8:); phloretic acid (9:); and luteolin (10:). Compounds 4:, 5:, 8:
      and 10: exhibited appreciable cytotoxic activity with 50% inhibitory
      concentration values less than 250 MUM. These compounds also showed potential
      apoptosis induction and anoikis-sensitizing effect at non-toxic concentrations.
      CONCLUSION: Compounds 4:, 5:, 8: and 10: are responsible for cytotoxic and anti
      metastatic activities of D. ellipsophyllum.

PMID- 25368261
TI  - End-of-life pain medication among cancer patients in hospice settings.
AB  - Cancer pain management in a hospice setting was studied in the present article.
      Drug treatments were studied at five time points: at the time of transfer to
      hospice, at 2nd day, two weeks, and two months following transfer to hospice
      care, as well as one day before death. PATIENTS AND METHODS: Records of 138
      consecutive cancer patients treated in hospice in 2010 were studied regarding the
      drugs given during their stay. The most common cancer was gastro-intestinal
      cancer (33%), followed by lung (16%) and breast cancer (11%). Data were collected
      from patients' records and coded in a validated manner for statistical analysis.
      RESULTS: The median length of stay in hospice was 14 days (range=2-376 days).
      Upon transfer, 63% of patients were administered regularly-dosed opioids, 76.8%
      during the second day at hospice, and 89.9% of the patients received opioids one
      day prior to death. A significant change was observed in the more frequent
      subcutaneous administration during hospice stay (p<0.0001). Break-through pain
      was recorded on the second day in hospice by 52 % of patients, and by 76% on the
      day prior to death. CONCLUSION: Individual patients' needs determined the dose
      range, but this was not the case for administration route of strong opioids
      during hospice care.

PMID- 25368263
TI  - Significance of self-reported symptoms as part of follow-up routines in patients
      treated for oral squamous cell carcinoma.
AB  - BACKGROUND: There is little evidence to prove that frequent out-patient
      consultations lead to better prognosis in patients treated for oral squamous cell
      carcinoma. Furthermore, there is no consensus regarding the timing and number of
      follow-up consultations or the duration of monitoring after completed therapy.
      MATERIALS AND METHODS: We prospectively recorded demographic and clinical data of
      537 patients treated over a period of 15 years with complete follow-up of 18
      years in a tertiary academic Center. RESULTS: Out of 537 patients considered free
      of disease after treatment, 196 (36%) developed recurrent disease during follow
      up. Self-reported symptoms led to diagnosis of the recurrence in 78% of the
      cases. Only 22% of recurrences were detected through physical examination of
      asymptomatic patients. There was no difference in disease-free survival in
      between these two groups. CONCLUSION: Follow-up routines are indispensable as
      part of cancer treatment but can be more cost-efficient when patients are
      educated and encouraged to report subjective symptoms. Trained personnel in
      collaboration with head and neck specialists can handle parts of follow-up
      routines.

PMID- 25368264
TI  - Role of interferon-alpha in patients with neuroendocrine tumors: a retrospective
      study.
AB  - BACKGROUND/AIM: Interferon alpha (IFNalpha) is used sparingly in the management
      of neuroendocrine tumors (NETs) due to toxicity and perceived limited efficacy.
      Other medical therapeutic options include somatostatin analogues and molecular
      targeted agents, as well as chemotherapy and radionuclide targeted-therapy. The
      aim of the present study was to perform a retrospective analysis of patients
      treated with IFNalpha. PATIENTS AND METHODS: Patients were identified from the
      NET database. Radiological, biochemical and symptomatic response were assessed.
      Progression-free survival (PFS), adverse events and toxicities were recorded.
      RESULTS: Thirty-five patients were treated with IFNalpha, with a mean age of 60.1
      (range=38-85) years; eight patients (23%) withdrew before 3 months, one (3%) had
      complete response; there was one partial response; 25 patients (71%) had at least
      three months of stable disease. The median PFS was 25 months. CONCLUSION:
      IFNalpha demonstrated efficacy and was reasonably tolerated. IFNalpha may still
      have a role in small-volume diffuse disease, in syndromic patients where there is
      resistance to somatostatin analogue, or as a bridge to other therapies.

PMID- 25368262
TI  - Adjuvant chemoradiation with 5-fluorouracil/leucovorin versus S-1 in gastric
      cancer patients following D2 lymph node dissection surgery: a feasibility study.
AB  - PURPOSE: We retrospectively analyzed the feasibility and adverse events for two
      regimens, postoperative chemoradiation (CRT) with 5-fluorouracil/leucovorin (5
      FU/LV) compared to S-1 in D2-resected gastric cancer patients. PATIENTS AND
      METHODS: The study included 405 gastric cancer patients who underwent curative
      gastrectomy with D2 lymph node dissection and received adjuvant therapy between
      January 2008 and July 2009. Feasibility and adverse events for the CRT and S-1
      regimens were analyzed. RESULTS: Out of the 405 patients, 244 (60.2%) had CRT and
      161 (39.8%) had S-1 treatment. The regimen was selected based on the preferences
      of the physician and the patient. S-1 was more frequently administered to
      patients with older age (age>=70) and those with early-stage disease (stage II).
      The stage was significantly more advanced in the CRT group compared to the S-1
      group (S-1 vs. CRT: stage II, 59.6% vs. 36.1%; stage III/IV, 28.0% vs. 48.3%,
      respectively; p<0.001). The completion rate of the planned therapy was
      significantly higher in the CRT group than in the S-1 group (95.1% vs. 72.8%,
      respectively; p<0.001). Regarding severe adverse events (grade 3-4), neutropenia
      (CRT vs. S-1; 40.2% vs. 8.7%, respectively, p<0.001), nausea (CRT vs. S-1; 5.7%
      vs. 0%, respectively; p=0.002) and stomatitis (CRT vs. S-1; 7.4% vs. 2.5%,
      respectively; p=0.034) were significantly more frequent in the CRT cohort
      compared to the S-1 group. CONCLUSION: Both adjuvant CRT with 5-FU/LV and
      adjuvant S-1 are safe and feasible in D2-resected gastric cancer patients.
      Patients with old age or early stage disease tend to prefer S-1 therapy to
      chemoradiation.

PMID- 25368265
TI  - Efficacy of nab-paclitaxel does not seem to be associated with SPARC expression
      in metastatic breast cancer.
AB  - AIM: To evaluate the predictive value of the expression of the secreted protein
      acidic and rich in cysteine (SPARC) for nab-paclitaxel in metastatic breast
      cancer (MBC). PATIENTS AND METHODS: Forty-four patients with progressive MBC were
      prospectively treated with nab-paclitaxel. Expression of SPARC in tumor cells was
      assessed by an immunoreactive score, integrating staining intensity and
      percentage of positive tumor cells; expression in stroma based on staining
      intensity. SPARC serum levels were determined before 1st and 2nd cycle of nab
      paclitaxel and at progression. By applying several cut-offs the association
      between SPARC expression or serum levels and clinical end-points was analyzed.
      RESULTS: No clear association between expression of SPARC in primary or
      metastatic tumor tissue or in serum and any clinical end-point could be detected
      regardless of the various cut-offs applied. CONCLUSION: Efficacy of nab
      paclitaxel in MBC does not seem to be associated with expression of SPARC in
      tumor tissues or serum.

PMID- 25368266
TI  - Clinical significance of pathological complete response in patients with
      metastatic gastrointestinal stromal tumors after imatinib mesylate treatment-
      lessons learned.
AB  - AIM: Imatinib mesylate (IM) has substantial efficacy in patients with metastatic
      gastrointestinal stromal tumors (GISTs), and pathological complete response (pCR)
      following IM treatment has been sporadically reported; however, its clinical
      significance for GIST needs to be clarified. PATIENTS AND METHODS: From 2001 to
      2010, 26 out of 171 patients with metastatic GIST who received IM with response
      or stable disease underwent operation. Among them, 12 operations with pCR were
      compared to 14 operations without pCR regarding clinicopathological features,
      mutation status, progression-free survival (PFS), and overall survival (OS).
      Following the operation, each tumor was assessed immunohistologically, and
      genetic analysis was performed on the tumor tissue. RESULTS: Twelve out of 26
      (46.2%) patients with metastatic GIST who received IM with response or stable
      disease had pCR. After a median follow-up of 40.8 months, patients with pCR had
      significantly better PFS and OS than those without pCR [2-year PFS and OS: 82.5%
      and 100% versus 35.6% and 49.4%, (p=0.014 and p=0.004) respectively]. Predictive
      factors for pCR were: origin of GIST, response after IM therapy, and duration of
      IM use before operation. Patients without pCR had a significantly higher
      frequency of secondary mutation when compared to those with pCR (47.4% versus 0%;
      p=0.004). CONCLUSION: Patients with colorectal GIST receiving IM who responded
      more quickly to IM treatment prior to surgery had a higher chance of pCR. pCR
      results in significantly favorable PFS and OS, however, IM cannot be withdrawn.
      Patients without pCR had a significantly higher frequency of secondary mutation
      when compared to those with pCR.

PMID- 25368267
TI  - Botulinum toxin for salivary disorders in the treatment of head and neck cancer.
AB  - BACKGROUND/AIM: During the treatment of head and neck cancer (HNC), salivary
      problems may impair a patient's healing process. Botulinum toxin (BoNT) is
      accepted as an effective treatment option for reducing salivary flow. We aimed to
      describe the features of patients treated with BoNT to determine the effects of
      BoNT. PATIENTS AND METHODS: Twenty-five patients over a five-year period were
      retrospectively included. The patients suffered at different stages of oncologic
      treatment. The cohort primarily had larger primary tumors that required complex
      oncological treatment. RESULTS: The condition improved in more than three
      quarters of the 19 patients with functional hypersalivation. Four of six cases
      suffering from a salivary fistula demonstrated an obvious reduction in symptoms.
      CONCLUSIONS: Injection of BoNT, to temporarily reduce saliva flow, is a safe tool
      in the treatment of HNC even in situations involving repeated therapy or high
      dosage. The main clinical side-effect of BoNT is insufficient reduction of the
      salivary problem.

PMID- 25368268
TI  - Liver resection in multimodal concepts improves survival of metastatic melanoma:
      a single-centre case-matched control study.
AB  - BACKGROUND/AIM: The aim of the present study was to define prognostic factors and
      to evaluate liver resection as an additive tool in metastatic melanoma. PATIENTS
      AND METHODS: In a case-control study, 32 patients with hepatic melanoma
      metastasis were analyzed between 1998-2012. Sixteen patients who underwent liver
      resection (6 patients with multimodal therapy) were matched to 16 patients
      scheduled for non-surgical approaches. Univariate and multivariate analyses were
      performed. RESULTS: Following primary resection and liver resection,
      respectively, survival was better for patients who underwent surgery in addition
      to multimodal therapy with 219 and 28 months, when compared to patients scheduled
      for non-surgical approaches with 64 (p=0.04) and 8 months (p=0.6). Following
      primary resection, primary tumor site, metastatic time <70 months, combination of
      multimodal therapy and surgery were of prognostic value (p<0.05). CONCLUSION:
      Liver resection should be considered a suitable additive tool in multimodal
      therapy of resectable metastatic melanoma.

PMID- 25368269
TI  - Survival after palliative radiotherapy in geriatric cancer patients.
AB  - BACKGROUND/AIM: Older cancer patients might experience inferior survival
      outcomes. However, no standard age cut-off is currently being used for commonly
      administered treatments such as radiotherapy. We evaluated survival outcomes and
      prognostic factors for survival after palliative radiotherapy (PRT) in our oldest
      patients (age>=80 years). PATIENTS AND METHODS: This retrospective study covered
      the time period between 2007 and 2012, and included 94 patients in this age group
      who were treated with PRT. Comparisons to a group of younger patients (31-79
      years of age, N=445) treated during the same time period were made. Uni- and
      multivariate analyses were also performed. Most patients received PRT for bone
      and brain metastases or in order to improve thoracic symptoms from lung cancer.
      RESULTS: Median age was 83 years. Survival outcomes and rates of PRT completion
      were not significantly different. Short median survival of less than 2 months was
      observed in two sub-groups of geriatric patients; those with brain metastases and
      those with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 4.
      Multivariate analysis confirmed the prognostic impact of PS, adrenal gland
      metastases, progressive disease outside PRT target volume(s), need for opioid
      analgetics and steroids (all p<0.05). Brain metastasis was associated with a
      borderline increase in risk of mortality (p=0.051). CONCLUSION: Our data support
      utilization of PRT irrespective of age for most patients with PS 0-3 but care
      should be taken in selecting the right fractionation regimen in order to avoid
      lengthy PRT courses when survival is limited.

PMID- 25368270
TI  - Relevance of calcitonin cut-off in the follow-up of medullary thyroid carcinoma
      for conventional imaging and 18-fluorine-fluorodihydroxyphenylalanine PET.
AB  - AIM: The American thyroid association (ATA) recommends that additional imaging
      procedures supplement cervical ultrasonography (US) in any patient with a basal
      calcitonin value above 150 pg/ml in the follow-up of medullary thyroid carcinoma
      (MTC). The aim of the present study was to reaffirm or challenge this cut-off for
      18-Fluorine-Fluorodihydroxyphenylalanine positron emission tomography (18F-DOPA
      PET) and conventional imaging ultrasonography (US), computed tomography (CT),
      magnetic resonance imaging (MRI)). MATERIALS AND METHODS: Thirty-nine patients
      (18 females, 21 males), mean age 62 years, range from 35 to 86, followed-up for
      MTC were included in the present retrospective study. In our patients 64 18F-DOPA
      scans, 28 neck US, 28 CT and 8 MRI were performed. For all cases basal calcitonin
      values were available. Sensitivity and specificity of 18F-DOPA PET and
      conventional imaging (US, CT, MRI) related to calcitonin values were calculated.
      RESULTS: According to the calcitonin cut-off of 150 pg/ml, we found the following
      sensitivities and specificities: 79% and 80% for 18F-DOPA PET, 75% and 92% for
      US, 80% and 25% for CT, 50% and 75% for MRI. Taking the level of detectable
      calcitonin, we calculated the following sensitivities: 52% for 18F-DOPA PET, 46%
      for US, 79% for CT and 38% for MRI. CONCLUSION: We cannot confirm the calcitonin
      cut-off proposed by the ATA for the detection of MTC recurrences and
      contemporaneously we cannot state that 18F-DOPA PET has a very high sensitivity.
      For the neck region 18F-DOPA PET and US showed similar results. 18F-DOPA PET/CT
      seems to be the best imaging modality for whole-body tumor detection. Bone
      metastases are best detected by MRI.

PMID- 25368271
TI  - Liver resectability of advanced liver-limited colorectal liver metastases
      following mFOLFOX6 with bevacizumab (KSCC0802 Study).
AB  - BACKGROUND/AIM: The Kyushu Study group of Clinical Cancer (KSCC) conducted phase
      II trials (KSCC0802-UMIN000001308) concerning liver resectability after first
      line treatment of advanced liver-limited colorectal metastases (CRLM) by a
      prospective, multi-center study. PATIENTS AND METHODS: Patients received 6 cycles
      of mFOLFOX6 with bevacizumab followed by evaluating liver resectability. The
      primary end-point was liver resection rate. RESULTS: The 40 patients enrolled
      from September 2008 to August 2010. The median number of administration cycles
      was 6 (range=1-7). The liver resectability cases were 16/40 (40.0 %) and the
      number of R0 cases was 10 patients (25.0%). An overall response rate was 30.0%
      (95% CI=15.2%-44.8%). Median progression-free and overall survival of all
      patients was 9.7 months and 33.0 months), respectively. CONCLUSION: mFOLFOX6 with
      bevacizumab regimen is safe and effective for advanced liver-limited CRLM and
      might lead to high liver resectability.

PMID- 25368272
TI  - Measurement of serum carcinoembryonic antigen, carbohydrate antigen 19-9,
      cytokeratin-19 fragment and matrix metalloproteinase-7 for detecting
      cholangiocarcinoma: a preliminary case-control study.
AB  - Cholangiocarcinoma is a malignant tumor of the liver arising from the bile duct
      epithelium, accounting for 10-25% of all primary hepatic cancers. The clinical
      presentation of this tumor is not specific and the diagnosis of early
      cholangiocarcinoma is difficult, especially in patients with other biliary
      diseases. Measurement of serum carbohydrate antigen (CA) 19-9 and
      carcinoembryonic antigen (CEA) are commonly used to monitor response to therapy,
      but are also useful for confirming the presence of a cholangiocarcinoma. In this
      setting, other biomarkers have been previously tested, including cytokeratin-19
      fragment (CYFRA 21-1) and the matrix metalloproteinase-7 (MMP7). The purpose of
      this retrospective study was to determine the clinical usefulness of the assay of
      serum CEA, CA 19-9, CYFRA 21-1 and MMP7, individually and together, as tumor
      markers for the diagnosis of cholangiocarcinoma. Twenty-four patients (14 men, 10
      women, 62.6+/-8.2 years of age) with histologically-confirmed cholangiocarcinoma
      (cases) and 25 age- and sex-matched patients with benign liver disease (controls)
      underwent measurement of these biomarkers. The mean values of all serum markers
      of patients with cholangiocarcinoma were significantly higher (p<0.01) than that
      of the controls. No correlation was found between serum tumor markers and total
      bilirubin, aspartate aminotransferase (AST) and alkaline phosphatase (ALP). The
      sensitivity, specificity and accuracy were: CEA: 52%, 55%, and 58%; CA 19-9: 74%,
      82% and 78%; CYFRA 21-1: 76%, 79% and 78%; MMP7: 78%, 77% and 80%, respectively.
      The combination of all serum markers afforded 92.0% sensitivity and 96%
      specificity in detecting cholangiocarcinoma, showing the highest diagnostic
      accuracy (94%). In conclusion, our preliminary results suggest that the
      measurement of all four biomarkers together can help in the early detection of
      cholangiocarcinoma. 

PMID- 25368273
TI  - Cancer diagnosis in a cohort of patients with Sjogren's syndrome and rheumatoid
      arthritis: a single-center experience and review of the literature.
AB  - BACKGROUND: With the development of modern therapies and better care of patients
      with autoimmune rheumatic diseases (ARDs) increased survival has been achieved.
      However, ARDs may share an association with risk of lymphomas and solid tumors.
      The increased cancer risk in these patients is mainly due to high inflammatory
      activity and severity of disease, rather than the immunosuppressive therapy.
      PATIENTS AND METHODS: We studied the coexistence or later development of cancer
      with ARDs in a retrospective audit of a reference university hospital and
      critically reviewed published literature. Fourteen out of 1,730 patients with
      rheumatoid arthritis (RA) and Sjogren's syndrome (SS) followed-up at the
      University Hospital of Ioannina over the last 33 years developed secondary
      malignancies, both solid tumors and lymphomas. RESULTS AND CONCLUSION: The most
      frequent cancer associated with ARDs is diffuse large B-cell lymphoma (DLBCL).
      The average risk of lymphoma in RA may be composed of a markedly increased risk
      in patients with most severe disease. Solid tumors were presented mainly in RA
      patients and renal cell carcinoma was the most frequently found.

PMID- 25368274
TI  - Does immediate breast reconstruction after mastectomy and neoadjuvant
      chemotherapy influence the outcome of patients with non-endocrine responsive
      breast cancer?
AB  - BACKGROUND/AIM: In breast cancer (BC) patients, breast surgery followed by
      immediate breast reconstruction (IBR) might favour recurrences and metastases due
      to extensive surgical manipulation. We retrospectively investigated whether IBR
      after mastectomy and neoadjuvant chemotherapy (NT) influenced the outcome in
      patients with early and locally advanced oestrogen receptor (ER)-negative BC.
      PATIENTS AND METHODS: Between 1995 and 2006, 133 BC patients received NT followed
      by total mastectomy, 59 of whom underwent IBR. Patients receiving IBR (IBR group)
      were compared to patients who did not receive IBR (no-IBR group) over a prolonged
      median follow-up time (8.2 years). RESULTS: Patients receiving IBR were on
      average younger than patients not receiving IBR (p<0.001). The percentage of
      patients with positive clinical nodal status (cN) was 19% in the IBR group and 7%
      in no-IBR group (p=0.036), whereas patients without IBR were more frequently
      diagnosed as clinical T4 (59% vs. 15%, p<0.001). The 5-year cumulative incidence
      of locoregional recurrences were 14% in the no-IBR group and 21% in the IBR
      group. The hazard of locoregional events, adjusted for age, clinical T and cN,
      was significantly greater in the IBR group than in the no-IBR group (hazard ratio
      (HR)=2.77, p=0.045). The 5-year cumulative incidences of distant metastases were
      similar in the two groups (p=0.414). CONCLUSION: IBR following total mastectomy
      in patients with ER-negative disease after NT is associated with a worse rate of
      local relapses. More insight in mechanisms of wound healing and extent of surgery
      is required to further investigate this observation.

PMID- 25368275
TI  - Chemoradiotherapy for extrahepatic bile duct cancer with gross residual disease
      after surgery.
AB  - BACKGROUND: The purpose of the present study was to analyze the outcome of
      chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients with gross
      residual disease after surgical resection. PATIENTS AND METHODS: We
      retrospectively analyzed 30 patients with EHBD adenocarcinoma who underwent
      chemoradiotherapy after palliative resection (R2 resection). Postoperative
      radiotherapy was delivered to the tumor bed including residual tumor and regional
      lymph nodes (range=40-55.8 Gy). Most patients underwent chemoradiotherapy
      concurrently with 5-fluorouracil (5-FU) or gemcitabine. RESULTS: The 2-year
      locoregional progression-free, distant metastasis-free and overall survival rates
      were 33.3%, 42.4% and 44.5%, respectively. High radiation dose>=50 Gy had a
      marginally significant impact on superior locoregional progression-free survival
      compared to 40 Gy (p=0.081). One patient developed grade 3 late gastrointestinal
      toxicity. CONCLUSION: Adjuvant chemoradiotherapy for EHBD cancer patients with
      gross residual disease after surgery was well-tolerated. There could be a chance
      for durable locoregional control and even long-term survival in selected
      patients.

PMID- 25368276
TI  - Detection of circulating tumor cells in breast cancer patients using multiplex
      reverse transcription-polymerase chain reaction and specific primers for MGB,
      PTHRP and KRT19 correlation with clinicopathological features.
AB  - AIM: The aim of this study was to correlate the clinicopathological features of
      breast cancer patients with the positive detection of parathyroid hormone-related
      protein (PTHRP), cytokeratin protein 19 (KRT19) and mammaglobin (MGB) using a
      multiplex reverse transcription polymerase chain reaction (RT-PCR) assay
      developed to detect circulating tumor cells (CTCs) in peripheral blood of
      patients with breast cancer. PATIENTS AND METHODS: Peripheral blood samples were
      collected from 54 breast cancer patients and 20 healthy blood donors.
      Subsequently, the samples were processed for RNA extraction and analyzed for the
      expression of PTHRP, KRT19 and MGB using specific primers and multiplex RT-PCR.
      RESULTS: The positive detection rates in breast cancer patients for PTHRP, KRT19
      and MGB were 68.5%, 63% and 22.2% and for healthy donors 10%, 0% and 10%,
      respectively. The statistical analysis revealed that PTHRP- and KRT19-positive
      detections correlated with the diagnosis of breast cancer while the combined
      positive detections of PTHRP-plus-KRT19 correlated with the presence of distant
      metastasis, especially with bone metastasis. Moreover, positive detections of
      KRT19 correlated with high proliferation rate of breast cancer tumors. MGB
      positive detections did not add any diagnostic advantage in such analysis.
      CONCLUSION: Multiplex-PCR based detection of CTCs using PTHRP and KRT19 primers
      can provide useful information for the disease.

PMID- 25368277
TI  - Radiotherapy for stage I/II follicular lymphoma (FL): is it time for a re
      appraisal?
AB  - AIM: Almost 30% of follicular lymphomas (FL) present with stage I-II disease.
      Although the standard-of-care consists of involved-field radiotherapy (IFRT),
      approximately half of patients relapse usually outside the primary irradiation
      field. Systemic immunotherapy with rituximab (R), with or without IFRT, could
      reduce distant recurrences leading to a better outcome. Therefore, we compared
      the efficacy of IFRT-alone or associated with R (R+IFRT) versus R-alone in stage
      I/II FL (grade 1-3A). PATIENTS AND METHODS: From 1995 to September 2012, 108
      early-stage FL patients were retrospectively assessed: 36 underwent IFRT, 38 R
      alone and 34 R+IFRT. RESULTS: Complete response rate was 84% in the IFRT-group,
      87% in the R group and 97% in the R+IFRT-group. Median progression-free survival
      and time to next treatment were significantly higher in both rituximab arms
      compared to IFRT-alone. CONCLUSION: R or R+IFRT have demonstrated a better long
      term control of the disease without significant additional toxicities.

PMID- 25368278
TI  - Circulating tumor cells as a biomarker predictive of sensitivity to docetaxel
      chemotherapy in patients with castration-resistant prostate cancer.
AB  - AIM: We examined whether Circulating Tumor Cells (CTCs) can be used to predict
      survival in patients with bone-metastatic castration-resistant-prostate cancer
      (mCRPC) treated with docetaxel chemotherapy. PATIENTS AND METHODS: All patients
      with mCRPC who had experienced treatment failure with androgen deprivation
      therapy and had received docetaxel chemotherapy were eligible for study
      inclusion. CTCs in whole blood were enumerated with the CellSearch System.
      RESULTS: The median CTC count at baseline before starting trial treatment was 7
      (range=0-227) CTCs per 7.5 ml blood. Out of the 57 patients, 24 (42.1%) had a CTC
      count of less than 5, while 27 patients (47.4%) had a CTC count of 5-50 and six
      patients (10.5%) had a CTC count of more than 50. A threshold of 5 or more CTCs
      per 7.5 ml blood was used to assess the ability to predict survival. The patient
      charts were examined to determine the median overall survival time, which ranged
      from 6 to 37 months (mean=12.8+/-8.1 months, median=15.3 months). Thirty-three
      patients (57.9%) had 5 or more CTCs before docetaxel chemotherapy, with a median
      overall survival of 10.5 months compared to 25.0 months for 24 patients (42.1%)
      with fewer than 5 CTCs (p<0.001). CTC and alkaline phosphatase (ALP) were
      independent predictors of overall survival time (p=0.004, and p=0.023,
      respectively). In addition, poorer overall survival was predicted by a CTC count
      of 5 or more after three courses of docetaxel chemotherapy. CONCLUSION: The CTC
      count may be an independent predictor of overall survival in patients with mCRPC
      treated with docetaxel chemotherapy. The numbers of CTCs detected was important
      in assessing response to chemotherapy and predict disease outcome.

PMID- 25368279
TI  - Evaluation of the contribution of cyclooxygenase 2 genotypes to breast cancer in
      Taiwan.
AB  - Overexpression of cyclooxygenase 2 (COX-2) has been suggested to be associated
      with breast carcinogenesis. The aim of the present study was to evaluate the
      contribution of genotypic polymorphisms in COX-2 to breast cancer risk of
      Taiwanese females. In total, 1,232 breast cancer patients and 1,232 healthy
      controls were genotyped by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) methodology. Six polymorphic variants of COX-2, including
      G-1195A (rs689466), G-765C (rs20417), T8473C (rs5275), intron 1 (rs2745557),
      intron 5 (rs16825748) and intron 6 (rs2066826) were examined. The results showed
      that the GC genotype of COX-2, G-765C was associated with a lower risk compared
      to the wild-type GG genotype (odds ratio(OR)=0.66, 95% confidence
      interval(CI)=0.53-0.83, p=0.0005). The C allele of COX-2 G-765C was significantly
      more frequently found in controls than in cancer patients (p=0.0006). In
      addition, the OR of the GG/AG+AA, GC/GG and GC/AG+AA at G-765C/Intron 1 combined
      genotypes compared to wild-type GG/GG genotype were 0.79 (95%CI=0.66-0.96;
      p=0.0166), 0.61 (95%CI=0.48-0.78; p=0.0001), and 0.71 (95%CI=0.36-1.37;
      p=0.3040), respectively. As for the combination of G-765C and intron 6, the OR of
      the GG/AG+AA, GC/GG and GC/AG+AA combined genotypes compared with wild-type GG/GG
      reference genotype were 0.79 (95%CI=0.62-1.01; p=0.0561), 0.63 (95%CI=0.50-0.81;
      p=0.0003), and 0.68 (95%CI=0.38-1.21; p=0.1897), respectively. Our results
      indicate that the C allele of COX-2, G-765C was associated with a decreased risk
      of breast cancer in Taiwan, and could serve as an early detection and predictive
      marker for breast cancer risk. 

PMID- 25368280
TI  - Gastric involvement in patients with primary mediastinal large B-cell lymphoma.
AB  - Gastric involvement is unusual in primary mediastinal large B-cell lymphoma
      (PMLBCL), which has not yet been adequately studied. The aim of this
      retrospective study was to investigate the frequency of gastric involvement in
      204 consecutive patients with PMLBCL that presented at 23 hospitals in Greece.
      Two out of 204 patients (1.0%) had gastric involvement at presentation. The first
      patient had symptomatic gastric disease manifested as upper gastrointestinal (GI)
      hemorrhage, which was the presenting symptom (first case reported in the
      literature). The second patient underwent positron emission tomography/computed
      tomography (PET/CT) at baseline staging which revealed abnormal gastric uptake.
      Histological examination revealed discordant lymphomatous involvement (MALT
      lymphoma, in a 33-year old female). The estimated frequency of gastric
      involvement by conventional staging was 1/204 (0.49%), but no cases were
      identified among asymptomatic patients. Among asymptomatic patients who underwent
      PET/CT at baseline staging, the PET/CT-based frequency of gastric involvement was
      7.1%, but lymphomatous gastric involvement was discordant. Finally, the frequency
      of gastric involvement in primary progressive or relapsed disease was 2.2%. Our
      study shows that gastric involvement is uncommon but can be seen in different
      clinical settings at presentation or at progression/relapse of PMLBCL. PET/CT
      based staging may provide more accurate information regarding the true incidence
      of sub-clinical gastric involvement in this entity, but histological confirmation
      is essential in order to confirm the diagnosis. 

PMID- 25368281
TI  - Long-term follow-up of borderline ovarian tumors clinical outcome and prognostic
      factors.
AB  - AIM: The aim of the present study was to evaluate the characteristics of
      borderline ovarian tumors (BOTs). PATIENTS AND METHODS: Data of 151 patients with
      BOTs were retrospectively evaluated. RESULTS: A total of 151 cases with BOTs were
      diagnosed. Histopathological evaluation identified 82.8% with serous, 10.6% with
      mucinous and 5.3% with mixed histology. Overall, 67.5% had International
      Federation of Gynecology and Obstetrics (FIGO) stage I, 10.6% FIGO stage II,
      14.6% FIGO stage III and 4% FIGO stage IV. A total of 21.9% had peritoneal
      implants; of which 2.7% were invasive, 17.2% non-invasive and 2% both invasive
      and non-invasive. Microinvasion was observed in 5.3% and a micropapillary pattern
      in 12.6%. A total of 12.6% of patients presented second neoplasms. During a
      median follow-up period of 86 (range=0.1-432) months, there were relapses in
      16.8%, of which 52.6% had invasive implants. Overall, 6.2% died of their disease,
      28.5% with invasive implants. The median time-to-progression was 48 (range=8-120)
      months. CONCLUSION: Patients with BOTs have an excellent prognosis. Long-term
      follow-up is recommended, since recurrence occurs.

PMID- 25368282
TI  - Vincristine-induced blindness: a case report and review of literature.
AB  - BACKGROUND: Neurotoxicity is a dose-limiting side-effect of vincristine therapy.
      Blindness is a rare central neurotoxicity of vincristine with few case reports.
      CASE REPORT: In the present article, we report a rare case of vincristine-induced
      blindness in a patient with diffuse large B cell lymphoma. Literature search
      identified eleven published cases of vincristine-induced blindness. We reviewed
      patient characteristics, chemotherapy used and type of blindness. CONCLUSION:
      Vincristine-induced blindness is rare and unpredictable. Prompt recognition and
      discontinuation of vincristine may lead to recovery of vision.

PMID- 25368283
TI  - Relevance of pelvic and para-aortic node metastases in early-stage ovarian
      cancer.
AB  - AIM: To delineate the relevance of pelvic and para-aortic node involvement in
      early-stage ovarian cancer. PATIENTS AND METHODS: Data on 75 consecutive patients
      with primary stage T1 and 2 ovarian cancer treated at the Department of
      Gynecology, University Tuebingen, Germany were retrospectively analyzed. All
      patients underwent stage-related surgery with pelvic and para-aortic
      lymphadenectomy and adjuvant platinum-based chemotherapy (except pT1aG1). Median
      follow up was 53.5 months. Clinico-pathological parameters and the distribution
      pattern of node metastases were evaluated. Statistical analyses were performed
      using PASW. RESULTS: Lymph node metastases were detectable in T1 and T2 in 6 (8%)
      of 75 patients. Three patients (4%) had lymph node metastases in the pelvic nodes
      only, 2 patients (2.7%) in the para-aortic nodes only; 1 patient (1.3%) both in
      the pelvic and para-aortic nodes. On multivariate analysis, histological grade 1/
      2 and 3 tumors, serous and endometrioid histology were independent predictors for
      node metastases, respectively. The risk of relapse was significantly higher with
      detection of node metastases (p=0.004). CONCLUSION: A systematic lymphadenectomy
      in early-stage ovarian cancer leads to an upstaging in a few patients after
      detection of node metastases even in pelvic or para-aortic nodes, especially in
      patients with grade 3 tumours and serous cancers. Pelvic and para-aortic
      lymphadenectomy may detect node involvement in early-stage ovarian cancer and
      might be helpful in correct staging.

PMID- 25368284
TI  - Impact of PSA levels on second-round screening for the development of prostate
      cancer in men with low baseline PSA levels (<=2.0 mg/ml).
AB  - BACKGROUND: To investigate the cumulative probability of developing prostate
      cancer according to prostate-specific antigen (PSA) velocity (PSAV) from first-to
      second-round PSA-based population screening in men with low baseline serum PSA
      levels. PATIENTS AND METHODS: A total of 11,913 men aged between 54 and 69 years
      with baseline PSA levels of <=2.0 ng/ml at the first population screening and who
      underwent population screening at least twice, were enrolled. The cumulative
      probability of developing prostate cancer according to age, baseline PSA and PSAV
      was investigated. The clinicopathological features of screen-detected cancer were
      also investigated. RESULTS: Out of the 11,913 men, 110 (0.92%) were
      pathologically diagnosed with prostate cancer during the observation period. The
      cumulative probability of developing prostate cancer in all participants after 5
      and 10 years was 0.64% and 1.79%, respectively. Univariate and multivariate
      analyses determined that baseline PSA levels and PSAVs were significant
      predictors of developing cancer and the hazard ratio increased with increasing
      baseline PSA levels and PSAVs. The optimal PSAV cut-off levels for prostate
      cancer development were 0.069, 0.106 and 0.285 for the baseline PSA ranges of 0.0
      1.0, 1.1-1.5 and 1.6-2.0 ng/ml, respectively. There were no significant
      differences in baseline PSA levels and PSAVs according to the clinical
      characteristics of the screen-detected prostate cancer patients. CONCLUSION: The
      present study demonstrated that serum PSA levels at second round screening were a
      strong predictor of cancer development in men with baseline PSA levels<=2.0 ng/ml
      at the first population screening.

PMID- 25368285
TI  - Fatal stimulation of acute myeloid leukemia blasts by pegfilgrastim.
AB  - We herein report the case of a male patient with acute myeloid leukemia with
      fatal outcome attributable to pharmacokinetics of pegfilgrastim. CASE REPORT: An
      unexplained blast proliferation in a patient with acute myeloid leukemia
      following cytotoxic induction chemotherapy was investigated in depth. Myeloblast
      hyperstimulation was likely related to pegfilgrastim, the long half-life of which
      extended the duration of side-effects, resulting in massive and rapidly fatal
      leukemia cell proliferation. CONCLUSION: Pegfilgrastim can cause unexpected
      deleterious effects in acute myeloid leukemia. We, thus, recommend administering
      drugs with a shorter half-life, such as filgrastim or lenograstim, to reduce
      infection incidence in patients receiving myelosuppressive chemotherapy
      associated with a clinically significant incidence of febrile neutropenia.

PMID- 25368286
TI  - Usefulness of MRI of microcalcification lesions to determine the indication for
      stereotactic mammotome biopsy.
AB  - BACKGROUND: With the recent rise in mammography (MMG) screenings there has been
      an increase in the identification of microcalcifications without lump. Therefore,
      a vacuum-assisted needle biopsy under stereotactic guidance (ST-MTB) is
      frequently performed for diagnosis. However, ST-MTB is a highly invasive
      examination. In this study, we investigated the effectiveness of utilizing
      contrast-enhanced magnetic resonance imaging (MRI) to differentiate between
      benign and malignant category 3 (C3) calcifications. MATERIALS AND METHODS: One
      hundred and sixty-eight patients with microcalcifications underwent contrast
      enhanced MRI prior to ST-MTB in our hospital. Their MRI scans were reviewed to
      determine whether the contrast-enhanced MRI findings were consistent. We
      calculated the sensitivity, specificity, positive predictive value (PPV) and
      negative predictive value (NPV) of contrast-enhanced MRI. RESULTS: No malignancy
      was not found in the 51 of the 168 cases analyzed by MRI. The calculated
      sensitivity, specificity, PPV and NPV of contrast-enhanced MRI were 84%, 82%, 58%
      and 95%, respectively. CONCLUSION: Contrast-enhanced MRI for Category 3 calcified
      lesions would be a useful diagnostic tool for identifying ST-MTB-indicated
      patients.

PMID- 25368287
TI  - Concurrent chemoradiotherapy with or without induction chemotherapy versus
      chemotherapy alone in patients with locally advanced pancreatic cancer.
AB  - BACKGROUND/AIM: The role of chemoradiotherapy (CRT) in the management of locally
      advanced pancreatic cancer is controversial. We aimed to explore this issue by
      retrospectively comparing the efficacy of concurrent CRT with or without
      induction (CT) versus CT alone in patients with locally advanced pancreatic
      cancer (LAPC). PATIENTS AND METHODS: Between January 2006 and December 2012, 55
      patients with biopsy-proven LAPC were treated either with CRT (n=31) or CT alone
      (n=24) at the authors' Institution. CT before or after CRT were allowed.
      Radiation therapy was delivered with a median dose of 50.4 Gy in a single
      fraction of 1.8 Gy and concurrent CT was typically given with gemcitabine at a
      dose of 400 mg/m2 weekly. The majority of CT was gemcitabine-based (96%).
      Progression-free survival and overall survival were calculated from the date of
      diagnosis to the date of progression and to the date of death or last follow-up,
      respectively. RESULTS: Patients' characteristics were not significantly different
      between the CRT group and CT-alone group. Nineteen (61%) patients received
      scheduled radiation dose of 50.4 Gy. The median cumulative dose of maintenance CT
      with gemcitabine after CRT was 6,500 mg/m2. The median survival was 14.6 versus
      8.1 months (p=0.001) and progression-free survival was 8.7 versus 4.9 months
      (p<0.001) for the CRT group and CT-alone group, respectively. CONCLUSION:
      Patients with LAPC treated with CRT conferred more favorable survival than those
      who did not receive CRT. CRT should be considered integrating into the management
      of LAPC.

PMID- 25368288
TI  - Predicting overall survival in patients with brain metastases from esophageal
      cancer.
AB  - AIM: To identify survival predictors and develop a survival score for patients
      with brain metastases from esophageal cancer. PATIENTS AND METHODS: In 16
      patients, seven factors were analyzed including age, gender, Karnofsky
      performance score (KPS), time from diagnosis of esophageal cancer to irradiation,
      number of brain metastases, histology, and presence of extracerebral metastases.
      RESULTS: Improved survival was significantly associated with KPS>=80 (p<0.001),
      the presence of one brain metastasis (p=0.007), and no extra-cerebral metastases
      (p=0.002). These factors were included in the final score. Factor scores were
      calculated by dividing 6-month survival rates by 10. Total survival scores
      represented the sums of factor scores and were 2, 7, 10, 19 or 24 points. Six
      month survival rates by score were 0%, 0%, 0%, 67% and 100%, respectively. Two
      groups were formed, those of patients with 2-10 points and those with 19-24
      points; 6-month survival was 0% and 88%, respectively (p<0.001). CONCLUSION: This
      new score facilitates the selection of individual therapies for patients with
      brain metastases from esophageal cancer.

PMID- 25368290
TI  - Safety and efficacy of radiofrequency ablation with aflibercept and FOLFIRI in a
      patient with metastatic colorectal cancer.
AB  - BACKGROUND: A vast majority of patients with metastatic colorectal cancer (mCRC)
      are not candidates for surgical resection. Radiofrequency ablation (RFA) is a
      safe and effective technique for treatment of isolated liver metastasis. After
      radiofrequency ablation, residual tumor can have aggressive growth, part of which
      is driven by the up-regulation of vascular endothelial growth factor (VEGF).
      Angiogenesis inhibitor bevacuzimab has been used in the management of mCRC with
      RFA. We present a patient with recurrent colorectal cancer and four hepatic
      metastases who was treated with RFA combined with aflibercept, another VEGF
      inhibitor and systemic chemotherapy. We believe that this is the first report of
      using aflibercept with RFA. CASE REPORT: A 35-year-old female with stage IV
      rectal cancer with metastasis to a lymph node and multiple hepatic metastases was
      treated with chemo-radiation, surgical resection of the tumor and surgical
      resection of two segments of the liver. She underwent RFA of the hepatic lesions
      that could not be resected. She received adjuvant chemotherapy consisting of 5
      fluorouracil (5-FU) and oxaliplatin for a total of 6 months. However, a positron
      emission tomography (PET) scan showed progression of disease with new and growing
      lymph nodes. She was treated with 6 cycles of capecitabine monotherapy. A follow
      up PET scan showed four new liver lesions. She has RFA of her four liver lesions
      and was started on a combination of aflibercept and FOLFIRI. She received 10
      cycles and a repeat magnetic resonance imaging (MRI) and PET scan showed stable
      disease. DISCUSSION: This is the first reported case of a patient managed with
      RFA with aflibercept, an anti-VEGF agent, and FOLFIRI. This case showed both
      efficacy, as well as safety for the combined modalities in the management of
      mCRC.

PMID- 25368291
TI  - Value of uroplakin III in distinguishing variants of primary bladder urothelial
      carcinoma from malignancy metastatic to the urinary bladder.
AB  - BACKGROUND: Urothelial carcinoma (UC) variants can be difficult to differentiate
      from carcinoma metastatic to the bladder. MATERIALS AND METHODS: We examined
      immunostaining for uroplakin III in 43 cases of primary bladder UC variants
      including micropapillary UC (n=19), nested variant of UC (n=2), pleomorphic giant
      cell carcinoma (n=8), plasmacytoid UC (n=4), lymphoepithelioma-like carcinoma
      (n=2), large cell undifferentiated carcinoma (n=2), UC with abundant myxoid
      stroma (n=3) and lipid cell variant (n=3) and in 11 tumors from other organs
      metastatic to the bladder. These tumors included invasive ductal carcinoma of the
      breast (n=2), colorectal adenocarcinoma (n=4), endometrioid adenocarcinoma (n=1)
      and serous papillary carcinoma of the uterus (n=1) melanoma (n=1), embryonal
      carcinoma of the testis (n=1), and renal clear cell carcinoma (n=1). RESULTS: Out
      of the 43 UC variants, 35 (81%) were positive for uroplakin III, including
      micropapillary, lipid cell variant and UC with abundant myxoid stroma.
      Pleomorphic giant cell carcinoma, plasmacytoid UC and nested variant of UC were
      less commonly positive. Of the 11 metastatic tumors, six were found to be
      positive for uropIakin III: metastatic colorectal adenocarcinoma, clear cell
      carcinoma of the kidney and embryonal carcinoma of testis. CONCLUSION: UP III
      Positivity for uroplakin III is not found only in primary bladder UC variants,
      but in some tumors that have metastatized to the bladder. Staining for uroplakin
      III alone should not be taken as evidence of UC.

PMID- 25368289
TI  - Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary
      locally advanced rectal cancer--a phase II clinical trial.
AB  - BACKGROUND/AIM: To investigate the feasibility and safety of preoperative
      capecitabine, cetuximab and radiation in patients with MRI-defined locally
      advanced rectal cancer (LARC, cT3/T4). PATIENTS AND METHODS: 31 patients with
      LARC were treated with cetuximab and capecitabine concomitantly with 45 Gy
      radiotherapy and resected by total mesorectal excision. Histopathological
      response and association with KRAS status was evaluated. RESULTS: R0-resection
      was possible in 27 of 31 (86%) patients. No complete pathological remission was
      observed. Radiochemotherapy with capecitabine and cetuximab was safe to
      administer and diarrhea was the main toxicity. KRAS-status did not correlate to
      down-staging or pathological response concerning T- or N-stage. CONCLUSION:
      Neoadjuvant therapy with capecitabine and cetuximab in combination with
      radiotherapy did not lead to complete pathological remission. Treatment
      tolerability was excellent and toxicity remained low. KRAS status did not
      influence treatment outcomes. Capecitabine in combination with radiotherapy
      remains a standard therapy for locally advanced rectal cancer.

PMID- 25368292
TI  - Hepatocellular carcinoma invading portal venous system in cirrhosis: long-term
      results of percutaneous radiofrequency ablation of both the nodule and portal
      vein tumor thrombus. A case control study.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related
      death. Portal vein tumor thrombus (PVTT) is one of the most dreadful
      complications of HCC and is associated with a median survival time of 2.7-4.0
      months. The optimal treatment for HCC with PVTT has not yet been established. The
      aim of the present study was to report long-term results of percutaneous
      radiofrequency (RF) ablation of both HCC single nodule (up to 5 cm in diameter)
      and neoplastic main portal vein thrombus, compared to no-treatment. PATIENTS AND
      METHODS: From January 2005 to January 2010, out of 2,847 consecutive cirrhosis
      patients, 672 had HCC and main portal vein tumor thrombus (MPVTT); among these,
      57 had a single HCC with MPVTT. Thirty-five patients with 35 single HCC nodules
      (ranging from 3.7 to 5 cm in diameter) underwent percutaneous RF ablation of both
      the nodule and the thrombus (cases); 22 patients refused RF ablation or any other
      treatment (controls). RESULTS: A complete necrosis of HCC nodules associated with
      re-canalization of main portal trunk (MPT) and its branches were observed in 26
      patients (success rate=74%). The 1-, 3- and 5-year cumulative survival rates of
      patients were 63%, 30% and 20%, respectively. The 12-month cumulative survival
      rate of controls was 0% (p<0.0001). The difference was statistically significant
      (p<0.001; harzard ratio (HR)=2.88; 95% confidence interval (CI)=1.57-5.39). The 3
      and 5-year cumulative disease-free survival rates of the patients were 35% and
      22%, respectively. No deaths occurred. CONCLUSION: RF ablation of HCC and the
      accompanying MPVTT significantly prolongs long-term survival compared to no
      treatment. The procedure is safe and should be considered as a new and effective
      tool in the treatment of advanced HCC.

PMID- 25368293
TI  - Multi-targeted approach to cancer treatment: an international translational
      cancer research symposium.
AB  - Whether it is chronic myeloid leukemia, ALK-expressing malignancies, or HER2
      positive breast cancer, targeted-therapies for treatment of human cancers have
      shown great promise. However, as they hit a single molecule expressed in
      neoplastic cells, their use is frequently associated with development of
      resistance. In cancer cells many signaling pathways operate in parallel, hence
      the idea of multi-targeted therapy is prevailing. The Society of Translational
      Cancer Research held its biennial meeting in the capital city of India, Delhi
      from February 6th through 9th, 2014 to discuss 'Multi-targeted Approach to
      Treatment of Cancer'. Over 200 scientists, clinicians, trainees, and industry
      representatives from different countries gathered in Vigyan Bhavan, the hotspot
      of Delhi for four days to talk and discuss on a variety of topics related to
      multi-targeted therapeutic approaches. Talks were presented by leaders in the
      cancer research field from various countries. It became clear from this
      conference that coupling multiple targeted-agents or using an agent that hits an
      individual target in several independent locations in the disease-causing
      pathway(s) may be the best approach to treat different cancers. 

PMID- 25368296
TI  - The root cause of a blistering eruption.

PMID- 25368297
TI  - Overlapping and complementary oxidative stress defense mechanisms in nontypeable
      Haemophilus influenzae.
AB  - The Gram-negative commensal bacterium nontypeable Haemophilus influenzae (NTHI)
      can cause respiratory tract diseases that include otitis media, sinusitis,
      exacerbations of chronic obstructive pulmonary disease, and bronchitis. During
      colonization and infection, NTHI withstands oxidative stress generated by
      reactive oxygen species produced endogenously, by the host, and by other
      copathogens and flora. These reactive oxygen species include superoxide, hydrogen
      peroxide (H2O2), and hydroxyl radicals, whose killing is amplified by iron via
      the Fenton reaction. We previously identified genes that encode proteins with
      putative roles in protection of the NTHI isolate strain 86-028NP against
      oxidative stress. These include catalase (HktE), peroxiredoxin/glutaredoxin
      (PgdX), and a ferritin-like protein (Dps). Strains were generated with mutations
      in hktE, pgdX, and dps. The hktE mutant and a pgdX hktE double mutant were more
      sensitive than the parent to killing by H2O2. Conversely, the pgdX mutant was
      more resistant to H2O2 due to increased catalase activity. Supporting the role of
      killing via the Fenton reaction, binding of iron by Dps significantly mitigated
      the effect of H2O2-mediated killing. NTHI thus utilizes several effectors to
      resist oxidative stress, and regulation of free iron is critical to this
      protection. These mechanisms will be important for successful colonization and
      infection by this opportunistic human pathogen. 

PMID- 25368299
TI  - Physiology and bioenergetics of [NiFe]-hydrogenase 2-catalyzed H2-consuming and
      H2-producing reactions in Escherichia coli.
AB  - Escherichia coli uptake hydrogenase 2 (Hyd-2) catalyzes the reversible oxidation
      of H2 to protons and electrons. Hyd-2 synthesis is strongly upregulated during
      growth on glycerol or on glycerol-fumarate. Membrane-associated Hyd-2 is an
      unusual heterotetrameric [NiFe]-hydrogenase that lacks a typical cytochrome b
      membrane anchor subunit, which transfers electrons to the quinone pool. Instead,
      Hyd-2 has an additional electron transfer subunit, termed HybA, with four
      predicted iron-sulfur clusters. Here, we examined the physiological role of the
      HybA subunit. During respiratory growth with glycerol and fumarate, Hyd-2 used
      menaquinone/demethylmenaquinone (MQ/DMQ) to couple hydrogen oxidation to fumarate
      reduction. HybA was essential for electron transfer from Hyd-2 to MQ/DMQ. H2
      evolution catalyzed by Hyd-2 during fermentation of glycerol in the presence of
      Casamino Acids or in a fumarate reductase-negative strain growing with glycerol
      fumarate was also shown to be dependent on both HybA and MQ/DMQ. The uncoupler
      carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited Hyd-2-dependent H2
      evolution from glycerol, indicating the requirement for a proton gradient. In
      contrast, CCCP failed to inhibit H2-coupled fumarate reduction. Although a Hyd-2
      enzyme lacking HybA could not catalyze Hyd-2-dependent H2 oxidation or H2
      evolution in whole cells, reversible H2-dependent reduction of viologen dyes
      still occurred. Finally, hydrogen-dependent dye reduction by Hyd-2 was reversibly
      inhibited in extracts derived from cells grown in H2 evolution mode. Our findings
      suggest that Hyd-2 switches between H2-consuming and H2-producing modes in
      response to the redox status of the quinone pool. Hyd-2-dependent H2 evolution
      from glycerol requires reverse electron transport. 

PMID- 25368298
TI  - The Vibrio cholerae Cpx envelope stress response senses and mediates adaptation
      to low iron.
AB  - The Cpx pathway, a two-component system that employs the sensor histidine kinase
      CpxA and the response regulator CpxR, regulates crucial envelope stress responses
      across bacterial species and affects antibiotic resistance. To characterize the
      CpxR regulon in Vibrio cholerae, the transcriptional profile of the pandemic V.
      cholerae El Tor C6706 strain was examined upon overexpression of cpxR. Our data
      show that the Cpx regulon of V. cholerae is enriched in genes encoding membrane
      localized and transport proteins, including a large number of genes known or
      predicted to be iron regulated. Activation of the Cpx pathway further led to the
      expression of TolC, the major outer membrane pore, and of components of two RND
      efflux systems in V. cholerae. We show that iron chelation, toxic compounds, or
      deletion of specific RND efflux components leads to Cpx pathway activation.
      Furthermore, mutations that eliminate the Cpx response or members of its regulon
      result in growth phenotypes in the presence of these inducers that, together with
      Cpx pathway activation, are partially suppressed by iron. Cumulatively, our
      results suggest that a major function of the Cpx response in V. cholerae is to
      mediate adaptation to envelope perturbations caused by toxic compounds and the
      depletion of iron. 

PMID- 25368300
TI  - Bacteriocin protein BacL1 of Enterococcus faecalis targets cell division loci and
      specifically recognizes L-Ala2-cross-bridged peptidoglycan.
AB  - Bacteriocin 41 (Bac41) is produced from clinical isolates of Enterococcus
      faecalis and consists of two extracellular proteins, BacL1 and BacA. We
      previously reported that BacL1 protein (595 amino acids, 64.5 kDa) is a
      bacteriolytic peptidoglycan D-isoglutamyl-L-lysine endopeptidase that induces
      cell lysis of E. faecalis when an accessory factor, BacA, is copresent. However,
      the target of BacL1 remains unknown. In this study, we investigated the targeting
      specificity of BacL1. Fluorescence microscopy analysis using fluorescent dye
      conjugated recombinant protein demonstrated that BacL1 specifically localized at
      the cell division-associated site, including the equatorial ring, division
      septum, and nascent cell wall, on the cell surface of target E. faecalis cells.
      This specific targeting was dependent on the triple repeat of the SH3 domain
      located in the region from amino acid 329 to 590 of BacL1. Repression of cell
      growth due to the stationary state of the growth phase or to treatment with
      bacteriostatic antibiotics rescued bacteria from the bacteriolytic activity of
      BacL1 and BacA. The static growth state also abolished the binding and targeting
      of BacL1 to the cell division-associated site. Furthermore, the targeting of
      BacL1 was detectable among Gram-positive bacteria with an L-Ala-L-Ala-cross
      bridging peptidoglycan, including E. faecalis, Streptococcus pyogenes, or
      Streptococcus pneumoniae, but not among bacteria with alternate peptidoglycan
      structures, such as Enterococcus faecium, Enterococcus hirae, Staphylococcus
      aureus, or Listeria monocytogenes. These data suggest that BacL1 specifically
      targets the L-Ala-L-Ala-cross-bridged peptidoglycan and potentially lyses the E.
      faecalis cells during cell division.

PMID- 25368301
TI  - In Salmonella enterica, the Gcn5-related acetyltransferase MddA (formerly YncA)
      acetylates methionine sulfoximine and methionine sulfone, blocking their toxic
      effects.
AB  - Protein and small-molecule acylation reactions are widespread in nature. Many of
      the enzymes catalyzing acylation reactions belong to the Gcn5-related N
      acetyltransferase (GNAT; PF00583) family, named after the yeast Gcn5 protein. The
      genome of Salmonella enterica serovar Typhimurium LT2 encodes 26 GNATs, 11 of
      which have no known physiological role. Here, we provide in vivo and in vitro
      evidence for the role of the MddA (methionine derivative detoxifier; formerly
      YncA) GNAT in the detoxification of oxidized forms of methionine, including
      methionine sulfoximine (MSX) and methionine sulfone (MSO). MSX and MSO inhibited
      the growth of an S. enterica DeltamddA strain unless glutamine or methionine was
      present in the medium. We used an in vitro spectrophotometric assay and mass
      spectrometry to show that MddA acetylated MSX and MSO. An mddA(+) strain
      displayed biphasic growth kinetics in the presence of MSX and glutamine. Deletion
      of two amino acid transporters (GlnHPQ and MetNIQ) in a DeltamddA strain restored
      growth in the presence of MSX. Notably, MSO was transported by GlnHPQ but not by
      MetNIQ. In summary, MddA is the mechanism used by S. enterica to respond to
      oxidized forms of methionine, which MddA detoxifies by acetyl coenzyme A
      dependent acetylation. 

PMID- 25368303
TI  - Antisense RNA amplification for target assessment of total mRNA from a single
      cell.
AB  - This protocol describes how to amplify mRNA isolated from a single cell and then
      analyze its gene expression profile using polymerase chain reaction (PCR). Single
      cell analysis is advantageous over studies of cell populations because it allows
      identification of a range of normal physiological states expressed by different
      cells of the same cell type without the confounding effects of averaging that
      result from measuring physiological states of cell populations. This is
      especially important when addressing questions of physiology in tissues, which
      comprises many different cell types. However, a single cell does not contain
      enough mRNA for all of the expressed transcripts to be detected or measured by
      any current molecular biology techniques. The antisense RNA (aRNA) amplification
      method was developed to amplify the picogram amounts of mRNA found within a
      single cell to microgram amounts of aRNA after three rounds of amplification.
      This aRNA can then easily be analyzed by microarray or next-generation
      sequencing. These methods allow identification of all expressed mRNA species
      within a single cell, including previously unknown mRNAs or those mRNAs
      specifically affected by a certain treatment. mRNA species of interest identified
      by these techniques can be further analyzed by designing primers targeting these
      species and performing PCR. cDNA synthesized from RNA at any stage in the aRNA
      amplification procedure, including material directly from collected unamplified
      cells, can be analyzed using PCR. Regardless of downstream applications, single
      cell aRNA amplification is a powerful tool for studying single-cell physiological
      dynamics.

PMID- 25368302
TI  - Universal response-adaptation relation in bacterial chemotaxis.
AB  - The bacterial strategy of chemotaxis relies on temporal comparisons of chemical
      concentrations, where the probability of maintaining the current direction of
      swimming is modulated by changes in stimulation experienced during the recent
      past. A short-term memory required for such comparisons is provided by the
      adaptation system, which operates through the activity-dependent methylation of
      chemotaxis receptors. Previous theoretical studies have suggested that efficient
      navigation in gradients requires a well-defined adaptation rate, because the
      memory time scale needs to match the duration of straight runs made by bacteria.
      Here we demonstrate that the chemotaxis pathway of Escherichia coli does indeed
      exhibit a universal relation between the response magnitude and adaptation time
      which does not depend on the type of chemical ligand. Our results suggest that
      this alignment of adaptation rates for different ligands is achieved through
      cooperative interactions among chemoreceptors rather than through fine-tuning of
      methylation rates for individual receptors. This observation illustrates a yet
      unrecognized function of receptor clustering in bacterial chemotaxis. 

PMID- 25368304
TI  - Two-photon photolysis combined with a kilobeam array scanner to probe calcium
      signaling in cardiomyocytes.
AB  - Photorelease of caged compounds allows a fast and defined intracellular increase
      in calcium (Ca(2+)) or other biologically relevant substances or molecules
      without impinging on other cellular functions. In particular, two-photon
      photolysis (2PP) allows a spatially restricted uncaging in sub-femtoliter
      volumes. Here, we describe how to combine 2PP with a confocal kilobeam array
      scanner and provide an example where Ca(2+) is released in an isolated cardiac
      myocyte. 

PMID- 25368305
TI  - Multi-beam two-photon imaging of fast Ca2+ signals in the Langendorff mouse
      heart.
AB  - Although the role of calcium (Ca(2+)) in excitation-contraction coupling in the
      heart can be comprehensively studied at the cellular level, propagation of Ca(2+)
      signals intercellularly requires tissue-based investigations. To access cells
      below the epicardium, an optical-sectioning technique is necessary. Multi-photon
      microscopy allows reliable imaging for penetration to depths of up to 0.5 mm.
      Here, we provide a protocol that uses multibeam two-photon microscopy for
      measuring Ca(2+) signals in a Langendorff-perfused mouse heart.

PMID- 25368306
TI  - Multi-channel imaging of cellular signaling: interplay of Ca2+ and conventional
      protein kinase C.
AB  - To investigate the coupling between the calcium (Ca(2+)) signal and the
      conventional protein kinase C alpha (PKCalpha) translocation, which are both
      transient processes, a sectioning imaging technique with sufficient scanning
      speed is required. Here, we describe how to use a Nipkow-disk-based confocal
      system with an image splitter for two cameras to acquire simultaneously both the
      Ca(2+) signal and images of PKCalpha fused to the fluorescent protein DsRed2 in
      HEK293 cells on ATP stimulation.

PMID- 25368307
TI  - Generation of high-titer RCAS virus from DF1 chicken fibroblasts.
AB  - RCAS viruses are replication-competent in avian cells, but are replication
      deficient in mammalian cells. Therefore, high-titer RCAS virus stocks can be
      generated only in avian cells. The chicken fibroblast cell line DF1 is well
      suited for this purpose. Successful infection of target mammalian cells,
      particularly in vivo, is dependent on the production of high titer viruses by DF1
      cells. Moreover, consistency in viral titer helps to ensure uniformity in results
      produced following the use of independent lots of virus producer cells.
      Therefore, it is critical to determine the viral titer before initiating these
      experiments. Because several factors, including insert size and the effect of the
      inserted gene product on the viability of DF1 cells, influence viral titer, the
      production of high virus titers cannot be assumed. For RCASBP-A-based viruses, a
      titer of >1 * 10(7) IU/mL is considered appropriate. Importantly, the virus
      reverse transcriptase is error prone; errors will accumulate in the virus
      produced over time. Therefore, virus producer cells should not be cultured for >4
      6 wk before being replaced with fresh producer cells. Low passage virus producer
      cells may be frozen and stored at -80 degrees C; thawed cells will not display a
      reduction in virus titer. Virus can be collected regularly, concentrated, and
      stored at -80 degrees C for long-term use; thawed viral stocks typically show a
      10-fold decrease in titer.

PMID- 25368308
TI  - In vivo delivery of RCAS virus to mice.
AB  - Injection of RCAS viruses is highly customizable to the desired target tissue.
      RCAS viruses can be delivered into mice in vivo by injection of virus-producing
      cells or by injection of concentrated virus. When cells are injected, they
      persist for several days, continuously producing virus. Typically the decision of
      whether to inject virus-producing cells or concentrated virus is determined by
      the volume that can be reliably injected into a given tissue and the age of the
      animal when the virus delivery is performed. This general protocol describes the
      intraperitoneal injection of RCAS-expressing cells into mice and discusses the
      circumstances in which the injection of concentrated virus is preferred.

PMID- 25368309
TI  - Reverse transcription-polymerase chain reaction.
AB  - Reverse transcription coupled to the polymerase chain reaction (RT-PCR) is
      commonly used to detect the presence of mRNAs, pre-mRNAs, or other types of RNA
      such as noncoding RNAs. The method involves using a primer annealed to the RNA of
      interest. For mRNA, the primer is usually a synthetic oligo(dT)15-18, a random
      hexamer mixture (dN)6, or a synthetic DNA oligonucleotide that is complementary
      to a specific transcript (a gene-specific primer). This DNA:RNA hybrid serves as
      a template during reverse transcription, in which the enzyme reverse
      transcriptase (RT) generates a single-stranded cDNA copy of a portion of the
      target RNA molecule. Using random hexamer priming, it is possible to obtain
      representative cDNA copies of sequences from the entire length of the mRNAs and
      pre-mRNAs in a population. This cDNA can then be used as a template for PCR. On
      addition of gene-specific primers, a specific DNA fragment corresponding to a
      portion of the RNA of interest is generated.

PMID- 25368310
TI  - Detection of apoptotic cells using immunohistochemistry.
AB  - Immunohistochemistry is commonly used to show the presence of apoptotic cells in
      situ. In this protocol, B-cell lymphoma cells are injected into recipient mice
      and, on tumor formation, the mice are treated with the apoptosis inducer
      vorinostat (a histone deacetylase inhibitor). Tumor samples are fixed and
      sectioned, and fragmented DNA (a feature of apoptotic cells) is end-labeled by
      terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL).
      Immunohistochemical methods are then used to detect the labeled DNA and identify
      B-cell lymphoma cells in the last stage of apoptosis. Because the assay can lead
      to false-positive results, it is advisable to carry out an additional assay
      (e.g., immunohistochemistry for active caspase-3) to confirm the presence of
      apoptotic cells. 

PMID- 25368311
TI  - Detection of apoptotic cells using propidium iodide staining.
AB  - Flow cytometry assays are often used to detect apoptotic cells in in vitro
      cultures. Depending on the experimental model, these assays can also be useful in
      evaluating apoptosis in vivo. In this protocol, we describe a propidium iodide
      (PI) flow cytometry assay to evaluate B-cell lymphomas that have undergone
      apoptosis in vivo. B-cell lymphoma cells are injected into recipient mice and, on
      tumor formation, the mice are treated with the apoptosis inducer vorinostat (a
      histone deacetylase inhibitor). Tumor samples collected from the lymph nodes
      and/or the spleen are used to prepare a single-cell suspension that is exposed to
      a hypotonic solution containing the fluorochrome PI. The DNA content of the
      cells, now labeled with PI, is analyzed by flow cytometry. Nuclear DNA content is
      lost during apoptosis, resulting in a hypodiploid (or sub-G1) DNA profile during
      flow cytometry. In contrast, healthy cells display a sharp diploid DNA profile.

PMID- 25368312
TI  - Isolating HeLa cell fractions enriched for clathrin-coated vesicles.
AB  - HeLa cell lines can be experimentally manipulated using drugs or gene-silencing
      techniques such as RNA interference. Fractions enriched for clathrin-coated
      vesicles (CCVs) can be isolated from these cell lines and used to study the
      effects of these manipulations on the composition of CCVs. This protocol,
      originally developed in the laboratory of Margaret Robinson (Cambridge, United
      Kingdom), describes the preparation of a HeLa cell fraction that is enriched for
      a mixed population of CCVs and is suitable for analysis by mass spectroscopy,
      western blotting, or electron microscopy. 

PMID- 25368313
TI  - Using in-gel digestion and an Orbitrap mass spectrometer to analyze the proteome
      of clathrin-coated vesicles.
AB  - The characterization of clathrin-coated vesicles (CCVs), including the effects of
      genetic or biochemical manipulations on their composition, can be studied by mass
      spectrometry analysis of HeLa cell fractions enriched for CCVs. This protocol
      describes the preparation of samples by tryptic in-gel digest and peptide
      extraction followed by analysis in an Orbitrap mass spectrometer.

PMID- 25368314
TI  - Using in-solution digestion, peptide fractionation, and a Q exactive mass
      spectrometer to analyze the proteome of clathrin-coated vesicles.
AB  - The characterization of clathrin-coated vesicles (CCVs), including the effects of
      genetic or biochemical manipulations on their composition, can be studied by mass
      spectrometry analysis of HeLa cell fractions enriched for CCVs. This protocol
      describes the preparation of samples by in-solution proteolytic digest and
      subsequent peptide fractionation, followed by analysis in a Q Exactive mass
      spectrometer.

PMID- 25368315
TI  - Using the RCAS-TVA system to model human cancer in mice.
AB  - For successful infection, avian sarcoma leukosis virus subgroup A (ASLV-A)
      requires its receptor, tumor virus A (TVA), to be present on the surface of
      target cells. This is the basis of the RCAS-TVA gene delivery system: Mammalian
      cells lack the gene encoding TVA and are normally resistant to infection by ASLV;
      however, transgenic targeting of TVA to specific cell types or tissues in the
      mouse renders these cells uniquely susceptible to infection by ASLV-A-based RCAS
      viruses. The RCAS-TVA system is a powerful tool for effectively modeling human
      tumors, including pancreatic, ovarian, and breast cancers, gliomas, and
      melanomas. RCAS viruses can deliver cDNAs (<=2.8 kb), as well as short hairpin
      RNAs (shRNAs), microRNAs (miRNAs), and other noncoding RNAs. Compared with
      traditional transgenic and knockout mice, the RCAS-TVA system has several
      strengths. First, virus delivery is generally performed postnatally and results
      in a relatively low infection rate of target cells; the sporadic postnatal
      expression of the gene of interest mimics the situation in developing human
      tumors. Second, a single transgenic mouse line can be used to compare the
      consequences of specific genes on tumor development, with viruses encoding
      oncogenes or shRNAs targeting specific tumor suppressor genes. TVA mouse strains
      can also be easily combined with transgenic, knock-in, and knockout mouse models
      to study cooperating genetic events. 

PMID- 25368316
TI  - Measuring apoptosis in mammals in vivo.
AB  - Apoptosis is a mode of cell death that is essential in multicellular organisms
      for the removal of superfluous, damaged, or potentially dangerous cells during
      development, infection, or normal tissue homeostasis. To prevent inflammation,
      cells undergoing apoptosis produce "find-me" signals that trigger the recruitment
      of phagocytes, which clear the apoptotic cells on recognition of "eat-me"
      signals. Despite the loss of billions of cells per day by apoptosis in the human
      body, the number of apoptotic cells found in healthy tissue is surprisingly low
      and reflects the efficiency of this process. However, in certain conditions
      (e.g., in cancer cells responding to chemotherapy), the number of apoptotic cells
      is too high to be efficiently cleared by phagocytes, and apoptotic cells can be
      observed. In these situations, the detection of apoptosis may be helpful in
      monitoring disease progression as well as in predicting the responses of tumors
      to anticancer therapies. Here we introduce various methods for monitoring
      apoptotic cells in vivo using a murine model of B-cell lymphoma and a solid tumor
      xenograft.

PMID- 25368317
TI  - Isolation of clathrin-coated vesicles from tissue culture cells.
AB  - The study of clathrin-coated vesicles (CCVs) isolated from various organs has
      revealed the identities and important features of many of the factors involved in
      membrane trafficking. The development of isolation methods using cultured cell
      lines has made it possible to manipulate the source material before isolation to
      ask important questions about the roles of these factors and the pathways in
      which they are involved. We discuss here the advantages and limitations of the
      use of cultured cell lines for the isolation of CCVs. 

PMID- 25368318
TI  - Methods for processing high-throughput RNA sequencing data.
AB  - High-throughput sequencing (HTS) methods for analyzing RNA populations (RNA-Seq)
      are gaining rapid application to many experimental situations. The steps in an
      RNA-Seq experiment require thought and planning, especially because the expense
      in time and materials is currently higher and the protocols are far less routine
      than those used for other high-throughput methods, such as microarrays. As
      always, good experimental design will make analysis and interpretation easier.
      Having a clear biological question, an idea about the best way to do the
      experiment, and an understanding of the number of replicates needed will make the
      entire process more satisfying. Whether the goal is capturing transcriptome
      complexity from a tissue or identifying small fragments of RNA cross-linked to a
      protein of interest, conversion of the RNA to cDNA followed by direct sequencing
      using the latest methods is a developing practice, with new technical
      modifications and applications appearing every day. Even more rapid are the
      development and improvement of methods for analysis of the very large amounts of
      data that arrive at the end of an RNA-Seq experiment, making considerations
      regarding reproducibility, validation, visualization, and interpretation
      increasingly important. This introduction is designed to review and emphasize a
      pathway of analysis from experimental design through data presentation that is
      likely to be successful, with the recognition that better methods are right
      around the corner. 

PMID- 25368319
TI  - Do patient-reported outcomes offer a more sensitive method for comparing the
      outcomes of consultants than mortality? A multilevel analysis of routine data.
AB  - BACKGROUND: Patient-reported outcome measures (PROM) might be better for
      comparing consultant surgeons' outcomes than mortality. OBJECTIVES: To describe
      variation in outcomes between consultants, compare the number of outlying
      consultants according to different measures, explore the effect that the hospital
      in which a consultant works has on their outcomes and determine the scope for
      improving outcomes by reducing variation between consultants. METHOD: Consultants
      performing hip replacement (n=948), knee replacement (1130) and hernia repair
      (974) in National Health Service hospitals in England in 2009-2012; disease
      specific and generic PROMs and complications; fixed-effects and multilevel models
      to assess consultant outcomes, were all compared. Influence of patient factors
      and hospital factors was assessed. RESULTS: Fixed-effects models showed that most
      consultants are 'as or better than expected'. However, unlike with mortality,
      some consultants are more than three SDs 'worse than expected' according to
      disease-specific PROMs (2.4% for hip and 1.2% for knee replacement), generic
      PROMs (1.2% and 1.0%) and incidence of complications (1.8% and 0.8%). The
      proportion of consultants worse than expected is less with random-effects models.
      Controlling for hospital factors reduced the proportion further. After
      controlling for known patient characteristics, consultants and hospitals
      contribute little towards variation in patient outcomes. CONCLUSIONS: PROMs offer
      a more appropriate and sensitive method for comparing consultants' outcomes. The
      influence of hospitals must be considered to ensure comparisons are meaningful.
      Improvements will be achieved by shifting the distribution of consultants rather
      than by reducing variation between them.

PMID- 25368320
TI  - Effectiveness of facilitated introduction of a standard operating procedure into
      routine processes in the operating theatre: a controlled interrupted time series.
AB  - BACKGROUND: Standard operating procedures (SOPs) should improve safety in the
      operating theatre, but controlled studies evaluating the effect of staff-led
      implementation are needed. METHODS: In a controlled interrupted time series, we
      evaluated three team process measures (compliance with WHO surgical safety
      checklist, non-technical skills and technical performance) and three clinical
      outcome measures (length of hospital stay, complications and readmissions) before
      and after a 3-month staff-led development of SOPs. Process measures were
      evaluated by direct observation, using Oxford Non-Technical Skills II for non
      technical skills and the 'glitch count' for technical performance. All staff in
      two orthopaedic operating theatres were trained in the principles of SOPs and
      then assisted to develop standardised procedures. Staff in a control operating
      theatre underwent the same observations but received no training. The change in
      difference between active and control groups was compared before and after the
      intervention using repeated measures analysis of variance. RESULTS: We observed
      50 operations before and 55 after the intervention and analysed clinical data on
      1022 and 861 operations, respectively. The staff chose to structure their efforts
      around revising the 'whiteboard' which documented and prompted tasks, rather than
      directly addressing specific task problems. Although staff preferred and
      sustained the new system, we found no significant differences in process or
      outcome measures before/after intervention in the active versus the control
      group. There was a secular trend towards worse outcomes in the postintervention
      period, seen in both active and control theatres. CONCLUSIONS: SOPs when
      developed and introduced by frontline staff do not necessarily improve operative
      processes or outcomes. The inherent tension in improvement work between giving
      staff ownership of improvement and maintaining control of direction needs to be
      managed, to ensure staff are engaged but invest energy in appropriate change.

PMID- 25368321
TI  - A short sequence motif in the 5' leader of the HIV-1 genome modulates extended
      RNA dimer formation and virus replication.
AB  - The 5' leader of the HIV-1 RNA genome encodes signals that control various steps
      in the replication cycle, including the dimerization initiation signal (DIS) that
      triggers RNA dimerization. The DIS folds a hairpin structure with a palindromic
      sequence in the loop that allows RNA dimerization via intermolecular kissing loop
      (KL) base pairing. The KL dimer can be stabilized by including the DIS stem
      nucleotides in the intermolecular base pairing, forming an extended dimer (ED).
      The role of the ED RNA dimer in HIV-1 replication has hardly been addressed
      because of technical challenges. We analyzed a set of leader mutants with a
      stabilized DIS hairpin for in vitro RNA dimerization and virus replication in T
      cells. In agreement with previous observations, DIS hairpin stability modulated
      KL and ED dimerization. An unexpected previous finding was that mutation of three
      nucleotides immediately upstream of the DIS hairpin significantly reduced in
      vitro ED formation. In this study, we tested such mutants in vivo for the
      importance of the ED in HIV-1 biology. Mutants with a stabilized DIS hairpin
      replicated less efficiently than WT HIV-1. This defect was most severe when the
      upstream sequence motif was altered. Virus evolution experiments with the
      defective mutants yielded fast replicating HIV-1 variants with second site
      mutations that (partially) restored the WT hairpin stability. Characterization of
      the mutant and revertant RNA molecules and the corresponding viruses confirmed
      the correlation between in vitro ED RNA dimer formation and efficient virus
      replication, thus indicating that the ED structure is important for HIV-1
      replication. 

PMID- 25368322
TI  - Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and
      promote functional myoblast differentiation.
AB  - GDF8, or myostatin, is a member of the TGF-beta superfamily of secreted
      polypeptide growth factors. GDF8 is a potent negative regulator of myogenesis
      both in vivo and in vitro. We found that GDF8 signaling was inhibited by the
      small molecule ATP competitive inhibitors dorsomorphin and LDN-193189. These
      compounds were previously shown to be potent inhibitors of BMP signaling by
      binding to the BMP type I receptors ALK1/2/3/6. We present the crystal structure
      of the type II receptor ActRIIA with dorsomorphin and demonstrate that
      dorsomorphin or LDN-193189 target GDF8 induced Smad2/3 signaling and repression
      of myogenic transcription factors. As a result, both inhibitors rescued
      myogenesis in myoblasts treated with GDF8. As revealed by quantitative live cell
      microscopy, treatment with dorsomorphin or LDN-193189 promoted the contractile
      activity of myotubular networks in vitro. We therefore suggest these inhibitors
      as suitable tools to promote functional myogenesis. 

PMID- 25368323
TI  - Functional analysis of insect molting fluid proteins on the protection and
      regulation of ecdysis.
AB  - Molting fluid accumulates between the old and new cuticles during periodical
      ecdysis in Ecdysozoa. Natural defects in insect ecdysis are frequently associated
      with melanization (an immunity response) occurring primarily in molting fluids,
      suggesting that molting fluid may impact immunity as well as affect ecdysis. To
      address this hypothesis, proteomic analysis of molting fluids from Bombyx mori
      during three different types of ecdysis was performed. Many proteins were newly
      identified, including immunity-related proteins, in each molting fluid. Molting
      fluids inhibited the growth of bacteria in vitro. The entomopathogenic fungi
      Beauveria bassiana, which can escape immune responses in feeding larvae, is
      quickly recognized by larvae during ecdysis, followed by melanization in molting
      fluid and old cuticle. Fungal conidia germination was delayed, and no hyphae were
      detected in the hemocoels of pharate instar insects. Molting fluids protect the
      delicate pharate instar insects with extremely thin cuticles against
      microorganisms. To explore the function of molting fluids in ecdysis regulation,
      based on protein similarity, 32 genes were selected for analysis in ecdysis
      regulation through RNAi in Tribolium castaneum, a model commonly used to study
      integument development because RNAi is difficult to achieve in B. mori. We
      identified 24 molting proteins that affected ecdysis after knockdown, with
      different physiological functions, including old cuticle protein recycling,
      molting fluid pressure balance, detoxification, and signal detection and transfer
      of molting fluids. We report that insects secrete molting fluid for protection
      and regulation of ecdysis, which indicates a way to develop new pesticides
      through interrupting insect ecdysis in the future. 

PMID- 25368324
TI  - The biosynthesis of UDP-d-FucNAc-4N-(2)-oxoglutarate (UDP-Yelosamine) in Bacillus
      cereus ATCC 14579: Pat and Pyl, an aminotransferase and an ATP-dependent Grasp
      protein that ligates 2-oxoglutarate to UDP-4-amino-sugars.
AB  - Surface glycan switching is often observed when micro-organisms transition
      between different biotic and abiotic niches, including biofilms, although the
      advantages of this switching to the organism are not well understood. Bacillus
      cereus grown in a biofilm-inducing medium has been shown to synthesize an unusual
      cell wall polysaccharide composed of the repeating subunit ->6)Gal(alpha1-2)(2-R
      hydroxyglutar-5-ylamido)Fuc2NAc4N(alpha1-6)GlcNAc(beta1->, where galactose is
      linked to the hydroxyglutarate moiety of FucNAc-4-amido-(2)-hydroxyglutarate. The
      molecular mechanism involved in attaching 2-hydroxyglutarate to 4-amino-FucNAc
      has not been determined. Here, we show two genes in B. cereus ATCC 14579 encoding
      enzymes involved in the synthesis of UDP-FucNAc-4-amido-(2)-oxoglutarate (UDP
      Yelosamine), a modified UDP-sugar not previously reported to exist. Using mass
      spectrometry and real time NMR spectroscopy, we show that Bc5273 encodes a C4"
      aminotransferase (herein referred to as Pat) that, in the presence of pyridoxal
      phosphate, transfers the primary amino group of l-Glu to C-4" of UDP-4-keto-6
      deoxy-d-GlcNAc to form UDP-4-amino-FucNAc and 2-oxoglutarate. Pat also converts 4
      keto-xylose, 4-keto-glucose, and 4-keto-2-acetamido-altrose to their
      corresponding UDP-4-amino-sugars. Bc5272 encodes a carboxylate-amine ligase
      (herein referred as Pyl) that, in the presence of ATP and Mg(II), adds 2
      oxoglutarate to the 4-amino moiety of UDP-4-amino-FucNAc to form UDP-Yelosamine
      and ADP. Pyl is also able to ligate 2-oxoglutarate to other 4-amino-sugar
      derivatives to form UDP-Yelose, UDP-Solosamine, and UDP-Aravonose. Characterizing
      the metabolic pathways involved in the formation of modified nucleotide sugars
      provides a basis for understanding some of the mechanisms used by bacteria to
      modify or alter their cell surface polysaccharides in response to changing growth
      and environmental challenges. 

PMID- 25368325
TI  - Systemic blockade of sialylation in mice with a global inhibitor of
      sialyltransferases.
AB  - Sialic acid terminates glycans of glycoproteins and glycolipids that play
      numerous biological roles in health and disease. Although genetic tools are
      available for interrogating the effects of decreased or abolished sialoside
      expression in mice, pharmacological inhibition of the sialyltransferase family
      has, to date, not been possible. We have recently shown that a sialic acid
      analog, 2,4,7,8,9-pentaacetyl-3Fax-Neu5Ac-CO2Me (3F-NeuAc), added to the media of
      cultured cells shuts down sialylation by a mechanism involving its intracellular
      conversion to CMP-3F-NeuAc, a competitive inhibitor of all sialyltransferases.
      Here we show that administering 3F-NeuAc to mice dramatically decreases
      sialylated glycans in cells of all tissues tested, including blood, spleen,
      liver, brain, lung, heart, kidney, and testes. A single dose results in greatly
      decreased sialoside expression for over 7 weeks in some tissues. Although
      blockade of sialylation with 3F-NeuAc does not affect viability of cultured
      cells, its use in vivo has a deleterious "on target" effect on liver and kidney
      function. After administration of 3F-NeuAc, liver enzymes in the blood are
      dramatically altered, and mice develop proteinuria concomitant with dramatic loss
      of sialic acid in the glomeruli within 4 days, leading to irreversible kidney
      dysfunction and failure to thrive. These results confirm a critical role for
      sialosides in liver and kidney function and document the feasibility of
      pharmacological inhibition of sialyltransferases for in vivo modulation of
      sialoside expression. 

PMID- 25368326
TI  - Isoliquiritigenin induces apoptosis and inhibits xenograft tumor growth of human
      lung cancer cells by targeting both wild type and L858R/T790M mutant EGFR.
AB  - Non-small-cell lung cancer (NSCLC) is associated with diverse genetic alterations
      including mutation of epidermal growth factor receptor (EGFR). Isoliquiritigenin
      (ILQ), a chalcone derivative, possesses anticancer activities. In the present
      study, we investigated the effects of ILQ on the growth of tyrosine kinase
      inhibitor (TKI)-sensitive and -resistant NSCLC cells and elucidated its
      underlying mechanisms. Treatment with ILQ inhibited growth and induced apoptosis
      in both TKI-sensitive and -resistant NSCLC cells. ILQ-induced apoptosis was
      associated with the cleavage of caspase-3 and poly-(ADP-ribose)-polymerase,
      increased expression of Bim, and reduced expression of Bcl-2. In vitro kinase
      assay results revealed that ILQ inhibited the catalytic activity of both wild
      type and double mutant (L858R/T790M) EGFR. Treatment with ILQ inhibited the
      anchorage-independent growth of NIH3T3 cells stably transfected with either wild
      type or double-mutant EGFR with or without EGF stimulation. ILQ also reduced the
      phosphorylation of Akt and ERK1/2 in both TKI-sensitive and -resistant NSCLC
      cells, and attenuated the kinase activity of Akt1 and ERK2 in vitro. ILQ directly
      interacted with both wild type and double-mutant EGFR in an ATP-competitive
      manner. A docking model study showed that ILQ formed two hydrogen bonds (Glu-762
      and Met-793) with wild type EGFR and three hydrogen bonds (Lys-745, Met-793, and
      Asp-855) with mutant EGFR. ILQ attenuated the xenograft tumor growth of H1975
      cells, which was associated with decreased expression of Ki-67 and diminished
      phosphorylation of Akt and ERK1/2. Taken together, ILQ suppresses NSCLC cell
      growth by directly targeting wild type or mutant EGFR. 

PMID- 25368327
TI  - Small ubiquitin-like modifier (SUMO)-mediated repression of the Xenopus Oocyte 5
      S rRNA genes.
AB  - The 5 S rRNA gene-specific transcription factor IIIA (TFIIIA) interacts with the
      small ubiquitin-like modifier (SUMO) E3 ligase PIAS2b and with one of its
      targets, the transcriptional corepressor, XCtBP. PIAS2b is restricted to the
      cytoplasm of Xenopus oocytes but relocates to the nucleus immediately after
      fertilization. Following the midblastula transition, PIAS2b and XCtBP are present
      on oocyte-type, but not somatic-type, 5 S rRNA genes up through the neurula
      stage, as is a limiting amount of TFIIIA. Histone H3 methylation, coincident with
      the binding of XCtBP, also occurs exclusively on the oocyte-type genes.
      Immunohistochemical staining of embryos confirms the occupancy of a subset of the
      oocyte-type genes by TFIIIA that become positioned at the nuclear periphery
      shortly after the midblastula transition. Inhibition of SUMOylation activity
      relieves repression of oocyte-type 5 S rRNA genes and is correlated with a
      decrease in methylation of H3K9 and H3K27 and disruption of subnuclear
      localization. These results reveal a novel function for TFIIIA as a negative
      regulator that recruits histone modification activity through the CtBP repressor
      complex exclusively to the oocyte-type 5 S rRNA genes, leading to their terminal
      repression. 

PMID- 25368328
TI  - A conserved three-nucleotide core motif defines Musashi RNA binding specificity.
AB  - Musashi (MSI) family proteins control cell proliferation and differentiation in
      many biological systems. They are overexpressed in tumors of several origins, and
      their expression level correlates with poor prognosis. MSI proteins control gene
      expression by binding RNA and regulating its translation. They contain two RNA
      recognition motif (RRM) domains, which recognize a defined sequence element. The
      relative contribution of each nucleotide to the binding affinity and specificity
      is unknown. We analyzed the binding specificity of three MSI family RRM domains
      using a quantitative fluorescence anisotropy assay. We found that the core
      element driving recognition is the sequence UAG. Nucleotides outside of this
      motif have a limited contribution to binding free energy. For mouse MSI1,
      recognition is determined by the first of the two RRM domains. The second RRM
      adds affinity but does not contribute to binding specificity. In contrast, the
      recognition element for Drosophila MSI is more extensive than the mouse homolog,
      suggesting functional divergence. The short nature of the binding determinant
      suggests that protein-RNA affinity alone is insufficient to drive target
      selection by MSI family proteins. 

PMID- 25368329
TI  - Human macrophage SCN5A activates an innate immune signaling pathway for antiviral
      host defense.
AB  - Pattern recognition receptors contain a binding domain for pathogen-associated
      molecular patterns coupled to a signaling domain that regulates transcription of
      host immune response genes. Here, a novel mechanism that links pathogen
      recognition to channel activation and downstream signaling is proposed. We
      demonstrate that an intracellular sodium channel variant, human macrophage SCN5A,
      initiates signaling and transcription through a calcium-dependent isoform of
      adenylate cyclase, ADCY8, and the transcription factor, ATF2. Pharmacological
      stimulation with a channel agonist or treatment with cytoplasmic poly(I:C), a
      mimic of viral dsRNA, activates this pathway to regulate expression of SP100
      related genes and interferon beta. Electrophysiological analysis reveals that the
      SCN5A variant mediates nonselective outward currents and a small, but detectable,
      inward current. Intracellular poly(I:C) markedly augments an inward voltage
      sensitive sodium current and inhibits the outward nonselective current. These
      results suggest human macrophage SCN5A initiates signaling in an innate immune
      pathway relevant to antiviral host defense. It is postulated that SCN5A is a
      novel pathogen sensor and that this pathway represents a channel activation
      dependent mechanism of transcriptional regulation. 

PMID- 25368335
TI  - Enhancing the value of MOC.

PMID- 25368336
TI  - SNMMI leadership update: The importance of quality, evidence, and value in
      nuclear medicine.

PMID- 25368330
TI  - Syk and Src family kinases regulate C-type lectin receptor 2 (CLEC-2)-mediated
      clustering of podoplanin and platelet adhesion to lymphatic endothelial cells.
AB  - The interaction of C-type lectin receptor 2 (CLEC-2) on platelets with Podoplanin
      on lymphatic endothelial cells initiates platelet signaling events that are
      necessary for prevention of blood-lymph mixing during development. In the present
      study, we show that CLEC-2 signaling via Src family and Syk tyrosine kinases
      promotes platelet adhesion to primary mouse lymphatic endothelial cells at low
      shear. Using supported lipid bilayers containing mobile Podoplanin, we further
      show that activation of Src and Syk in platelets promotes clustering of CLEC-2
      and Podoplanin. Clusters of CLEC-2-bound Podoplanin migrate rapidly to the center
      of the platelet to form a single structure. Fluorescence lifetime imaging
      demonstrates that molecules within these clusters are within 10 nm of one another
      and that the clusters are disrupted by inhibition of Src and Syk family kinases.
      CLEC-2 clusters are also seen in platelets adhered to immobilized Podoplanin
      using direct stochastic optical reconstruction microscopy. These findings provide
      mechanistic insight by which CLEC-2 signaling promotes adhesion to Podoplanin and
      regulation of Podoplanin signaling, thereby contributing to lymphatic vasculature
      development. 

PMID- 25368331
TI  - Tipping the MYC-MIZ1 balance: targeting the HUWE1 ubiquitin ligase selectively
      blocks MYC-activated genes.
AB  - MYC family oncoproteins (MYC, N-MYC and L-MYC) function as basic helix-loop-helix
      leucine zipper (bHLH-Zip) transcription factors that are activated (i.e.,
      overexpressed) in well over half of all human malignancies (Boxer & Dang, 2001;
      Beroukhim et al, 2010). In this issue of EMBO Molecular Medicine, Eilers and
      colleagues (Peter et al, 2014) describe a novel approach to disable MYC, whereby
      inhibition of the ubiquitin ligase HUWE1 stabilizes MIZ1 and leads to the
      selective repression of MYC-activated target genes.

PMID- 25368337
TI  - 2014 SNMMI highlights lecture: Oncology.

PMID- 25368338
TI  - Perceptual learning of contrast discrimination under roving: the role of semantic
      sequence in stimulus tagging.
AB  - Perceptual learning may occur when multiple contrasts are practiced in a fixed,
      but not in a roving (random), temporal sequence. However, learning may escape
      roving disruption when each contrast is assigned a letter tag (i.e., A, B, C, D).
      Because these letter tags carry not only stimulus identity information, but also
      semantic sequence information, here we investigated whether the semantic sequence
      information is necessary for learning of tagged contrasts under the roving
      condition. We found that assigning number tags (i.e., 1, 2, 3, 4), which also
      contained both identity and semantic sequence information, to four roving
      contrasts enabled significant learning of discrimination of each contrast,
      confirming previous data. However, learning became insignificant when the
      contrast tags were replaced with Greek letters that were familiar to our Chinese
      observers except their sequence or Chinese characters that carried no sequence
      information. In addition, assigning orientation tags, which carried no sequence
      information either, to roving contrasts was ineffective as well because learning
      occurred only with sequenced but not roving contrasts. These results suggest that
      semantic sequence information is necessary for stimulus tagging to effectively
      enable perceptual learning of multiple contrast discrimination under roving. 

PMID- 25368339
TI  - Characterizing the effects of multidirectional motion adaptation.
AB  - Recent sensory experience can alter our perception and change the response
      characteristics of sensory neurons. These effects of sensory adaptation are a
      ubiquitous property of perceptual systems and are believed to be of fundamental
      importance to sensory coding. Yet we know little about how adaptation to stimulus
      ensembles affects our perception of the environment as most psychophysical
      experiments employ adaptation protocols that focus on prolonged exposure to a
      single visual attribute. Here, we investigate how concurrent adaptation to
      multiple directions of motion affects perception of subsequently presented motion
      using the direction aftereffect. In different conditions, observers adapted to a
      stimulus ensemble comprised of dot directions sampled from different
      distributions or to bidirectional motion. Increasing the variance of normally
      distributed directions reduced the magnitude of the peak direction aftereffect
      and broadened its tuning profile. Sampling of asymmetric Gaussian and uniform
      distributions resulted in shifts of direction aftereffect tuning profiles
      consistent with changes in the perceived global direction of the adapting
      stimulus. Adding dots in a direction opposite or orthogonal to a unidirectional
      adapting stimulus led to a pronounced reduction in the direction aftereffect. A
      simple population-coding model, in which adaptation selectively alters the
      responsivity of direction-selective neurons, can accommodate the effects of
      multidirectional adaptation on the perceived direction of motion. 

PMID- 25368340
TI  - N-methyl-D-aspartate receptor channel blocker-like discriminative stimulus
      effects of nitrous oxide gas.
AB  - Nitrous oxide (N2O) gas is a widely used anesthetic adjunct in dentistry and
      medicine that is also commonly abused. Studies have shown that N2O alters the
      function of the N-methyl-d-aspartate (NMDA), GABAA, opioid, and serotonin
      receptors among others. However, the receptors systems underlying the abuse
      related central nervous system effects of N2O are unclear. The present study
      explores the receptor systems responsible for producing the discriminative
      stimulus effects of N2O. B6SJLF1/J male mice trained to discriminate 10 minutes
      of exposure to 60% N2O + 40% oxygen versus 100% oxygen served as subjects. Both
      the high-affinity NMDA receptor channel blocker (+)-MK-801 maleate [(5S,10R)-(+)
      5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] and the low
      affinity blocker memantine partially mimicked the stimulus effects of N2O.
      Neither the competitive NMDA antagonist, CGS-19755 (cis-4-[phosphomethyl]
      piperidine-2-carboxylic acid), nor the NMDA glycine-site antagonist, L701-324 [7
      chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(1H)-quinolinone], produced N2O-like
      stimulus effects. A range of GABAA agonists and positive modulators, including
      midazolam, pentobarbital, muscimol, and gaboxadol (4,5,6,7
      tetrahydroisoxazolo[4,5-c]pyridine-3-ol), all failed to produce N2O-like stimulus
      effects. The MU-, kappa-, and delta-opioid agonists, as well as 5
      hydroxytryptamine (serotonin) 1B/2C (5-HT1B/2C) and 5-HT1A agonists, also failed
      to produce N2O-like stimulus effects. Ethanol partially substituted for N2O. Both
      (+)-MK-801 and ethanol but not midazolam pretreatment also significantly enhanced
      the discriminative stimulus effects of N2O. Our results support the hypothesis
      that the discriminative stimulus effects of N2O are at least partially mediated
      by NMDA antagonist effects similar to those produced by channel blockers.
      However, as none of the drugs tested fully mimicked the stimulus effects of N2O,
      other mechanisms may also be involved. 

PMID- 25368341
TI  - Comparison of dose-volume histograms between proton beam and X-ray conformal
      radiotherapy for locally advanced non-small-cell lung cancer.
AB  - The purpose of this study was to compare the parameters of the dose-volume
      histogram (DVH) between proton beam therapy (PBT) and X-ray conformal
      radiotherapy (XCRT) for locally advanced non-small-cell lung cancer (NSCLC),
      according to the tumor conditions. A total of 35 patients having NSCLC treated
      with PBT were enrolled in this analysis. The numbers of TNM stage and lymph node
      status were IIB (n = 3), IIIA (n = 15) and IIIB (n = 17), and N0 (n = 2), N1 (n =
      4), N2 (n = 17) and N3 (n = 12), respectively. Plans for XCRT were simulated
      based on the same CT, and the same clinical target volume (CTV) was used based on
      the actual PBT plan. The treatment dose was 74 Gy-equivalent dose (GyE) for the
      primary site and 66 GyE for positive lymph nodes. The parameters were then
      calculated according to the normal lung dose, and the irradiation volumes of the
      doses (Vx) were compared. We also evaluated the feasibility of both plans
      according to criteria: V5 >= 42%, V20 >= 25%, mean lung dose >= 20 Gy. The mean
      normal lung dose and V5 to V50 were significantly lower in PBT than in XCRT. The
      differences were greater with the more advanced nodal status and with the larger
      CTV. Furthermore, 45.7% of the X-ray plans were classified as inadequate
      according to the criteria, whereas 17.1% of the proton plans were considered
      unsuitable. The number of inadequate X-ray plans increased in cases with advanced
      nodal stage. This study indicated that some patients who cannot receive photon
      radiotherapy may be able to be treated using PBT. 

PMID- 25368343
TI  - Raman spectroscopy as a screening tool for ancient life detection on Mars.
AB  - The search for sp(2)-bonded carbonaceous material is one of the major life
      detection strategies of the astrobiological exploration programmes of National
      Aeronautics and Space Administration and European Space Agency (ESA). The ESA
      ExoMars rover scheduled for launch in 2018 will include a Raman spectrometer with
      the goal of detecting sp(2)-bonded carbonaceous material as potential evidence of
      ancient life. However, sp(2)-bonded carbonaceous material will yield the same
      Raman spectra of well-developed G and D bands whether they are synthesized
      biologically or non-biologically. Therefore, the origin and source of sp(2)
      bonded carbonaceous material cannot be elucidated by Raman spectroscopy alone.
      Here, we report the combined approach of Raman spectroscopy and gas
      chromatography-mass spectrometry biomarker analysis to Precambrian sedimentary
      rocks, which taken together, provides a promising new methodology for readily
      detecting and rapidly screening samples for immature organic material amenable to
      successful biomarker analysis. 

PMID- 25368342
TI  - Whole-thorax irradiation induces hypoxic respiratory failure, pleural effusions
      and cardiac remodeling.
AB  - To study the mechanisms of death following a single lethal dose of thoracic
      radiation, WAG/RijCmcr (Wistar) rats were treated with 15 Gy to the whole thorax
      and followed until they were morbid or sacrificed for invasive assays at 6 weeks.
      Lung function was assessed by breathing rate and arterial oxygen saturation. Lung
      structure was evaluated histologically. Cardiac structure and function were
      examined by echocardiography. The frequency and characteristics of pleural
      effusions were determined. Morbidity from 15 Gy radiation occurred in all rats 5
      to 8 weeks after exposure, coincident with histological pneumonitis. Increases in
      breathing frequencies peaked at 6 weeks, when profound arterial hypoxia was also
      recorded. Echocardiography analysis at 6 weeks showed pulmonary hypertension and
      severe right ventricular enlargement with impaired left ventricular function and
      cardiac output. Histologic sections of the heart revealed only rare foci of
      lymphocytic infiltration. Total lung weight more than doubled. Pleural effusions
      were present in the majority of the irradiated rats and contained elevated
      protein, but low lactate dehydrogenase, when compared with serum from the same
      animal. Pleural effusions had a higher percentage of macrophages and large
      monocytes than neutrophils and contained mast cells that are rarely present in
      other pathological states. Lethal irradiation to rat lungs leads to hypoxia with
      infiltration of immune cells, edema and pleural effusion. These changes may
      contribute to pulmonary vascular and parenchymal injury that result in secondary
      changes in heart structure and function. We report that conditions resembling
      congestive heart failure contribute to death during radiation pneumonitis, which
      indicates new targets for therapy. 

PMID- 25368344
TI  - Miniaturized Raman instrumentation detects carotenoids in Mars-analogue rocks
      from the Mojave and Atacama deserts.
AB  - This study is primarily focused on proving the potential of miniaturized Raman
      systems to detect any biomolecular and mineral signal in natural geobiological
      samples that are relevant for future application of the technique within
      astrobiologically aimed missions on Mars. A series of evaporites of varying
      composition and origin from two extremely dry deserts were studied, namely
      Atacama and Mojave. The samples represent both dry evaporitic deposits and recent
      evaporitic efflorescences from hypersaline brines. The samples comprise halite
      and different types of sulfates and carbonates. The samples were analysed in two
      different ways: (i) directly as untreated rocks and (ii) as homogenized powders.
      Two excitation wavelengths of miniaturized Raman spectrometers were compared: 532
      and 785 nm. The potential to detect carotenoids as biomarkers on Mars compared
      with the potential detection of carbonaceous matter using miniaturized
      instrumentation is discussed. 

PMID- 25368345
TI  - Mineralogical analyses of surface sediments in the Antarctic Dry Valleys:
      coordinated analyses of Raman spectra, reflectance spectra and elemental
      abundances.
AB  - Surface sediments at Lakes Fryxell, Vanda and Brownworth in the Antarctic Dry
      Valleys (ADV) were investigated as analogues for the cold, dry environment on
      Mars. Sediments were sampled from regions surrounding the lakes and from the ice
      cover on top of the lakes. The ADV sediments were studied using Raman spectra of
      individual grains and reflectance spectra of bulk particulate samples and
      compared with previous analyses of subsurface and lakebottom sediments. Elemental
      abundances were coordinated with the spectral data in order to assess trends in
      sediment alteration. The surface sediments in this study were compared with
      lakebottom sediments (Bishop JL et al. 2003 Int. J. Astrobiol. 2, 273-287
      (doi:10.1017/S1473550403001654)) and samples from soil pits (Englert P et al.
      2013 In European Planetary Science Congress, abstract no. 96; Englert P et al.
      2014 In 45th Lunar and Planetary Science Conf., abstract no. 1707). Feldspar,
      quartz and pyroxene are common minerals found in all the sediments. Minor
      abundances of carbonate, chlorite, actinolite and allophane are also found in the
      surface sediments, and are similar to minerals found in greater abundance in the
      lakebottom sediments. Surface sediment formation is dominated by physical
      processes; a few centimetres below the surface chemical alteration sets in,
      whereas lakebottom sediments experience biomineralization. Characterizing the
      mineralogical variations in these samples provides insights into the alteration
      processes occurring in the ADV and supports understanding alteration in the cold
      and dry environment on Mars. 

PMID- 25368346
TI  - Raman spectroscopic identification of scytonemin and its derivatives as key
      biomarkers in stressed environments.
AB  - Raman spectroscopy has been identified as an important first-pass analytical
      technique for deployment on planetary surfaces as part of a suite of
      instrumentation in projected remote space exploration missions to detect extant
      or extinct extraterrestrial life signatures. Aside from the demonstrable
      advantages of a non-destructive sampling procedure and an ability to record
      simultaneously the molecular signatures of biological, geobiological and
      geological components in admixture in the geological record, the interrogation
      and subsequent interpretation of spectroscopic data from these experiments will
      be critically dependent upon the recognition of key biomolecular markers
      indicative of life existing or having once existed in extreme habitats. A
      comparison made with the characteristic Raman spectral wavenumbers obtained from
      standards is not acceptable because of shifts that can occur in the presence of
      other biomolecules and their host mineral matrices. In this paper, we identify
      the major sources of difficulty experienced in the interpretation of
      spectroscopic data centring on a key family of biomarker molecules, namely
      scytonemin and its derivatives; the parent scytonemin has been characterized
      spectroscopically in cyanobacterial colonies inhabiting some of the most extreme
      terrestrial environments and, with the support of theoretical calculations,
      spectra have been predicted for the characterization of several of its
      derivatives which could occur in novel extraterrestrial environments. This work
      will form the foundation for the identification of novel biomarkers and for their
      Raman spectroscopic discrimination, an essential step in the interpretation of
      potentially complex and hitherto unknown biological radiation protectants based
      on the scytoneman and scytonin molecular skeletons which may exist in niche
      geological scenarios in the surface and subsurface of planets and their
      satellites in our Solar System.

PMID- 25368347
TI  - Halophilic archaea on Earth and in space: growth and survival under extreme
      conditions.
AB  - Salts are abundant on Mars, and any liquid water that is present or may have been
      present on the planet is expected to be hypersaline. Halophilic archaea (family
      Halobacteriaceae) are the microorganisms best adapted to life at extremes of
      salinity on Earth. This paper reviews the properties of the Halobacteriaceae that
      may make the group good candidates for life also on Mars. Many species resist
      high UV and gamma radiation levels; one species has survived exposure to vacuum
      and radiation during a space flight; and there is at least one psychrotolerant
      species. Halophilic archaea may survive for millions of years within brine
      inclusions in salt crystals. Many species have different modes of anaerobic
      metabolism, and some can use light as an energy source using the light-driven
      proton pump bacteriorhodopsin. They are also highly tolerant to perchlorate,
      recently shown to be present in Martian soils, and some species can even use
      perchlorate as an electron acceptor to support anaerobic growth. The presence of
      characteristic carotenoid pigments (alpha-bacterioruberin and derivatives) makes
      the Halobacteriaceae easy to identify by Raman spectroscopy. Thus, if present on
      Mars, such organisms may be detected by Raman instrumentation planned to explore
      Mars during the upcoming ExoMars mission.

PMID- 25368348
TI  - Potential and limits of Raman spectroscopy for carotenoid detection in
      microorganisms: implications for astrobiology.
AB  - In this paper, it is demonstrated how Raman spectroscopy can be used to detect
      different carotenoids as possible biomarkers in various groups of microorganisms.
      The question which arose from previous studies concerns the level of unambiguity
      of discriminating carotenoids using common Raman microspectrometers. A series of
      laboratory-grown microorganisms of different taxonomic affiliation was
      investigated, such as halophilic heterotrophic bacteria, cyanobacteria, the
      anoxygenic phototrophs, the non-halophilic heterotrophs as well as eukaryotes
      (Ochrophyta, Rhodophyta and Chlorophyta). The data presented show that Raman
      spectroscopy is a suitable tool to assess the presence of carotenoids of these
      organisms in cultures. Comparison is made with the high-performance liquid
      chromatography approach of analysing pigments in extracts. Direct measurements on
      cultures provide fast and reliable identification of the pigments. Some of the
      carotenoids studied are proposed as tracers for halophiles, in contrast with
      others which can be considered as biomarkers of other genera. The limits of
      application of Raman spectroscopy are discussed for a few cases where the current
      Raman spectroscopic approach does not allow discriminating structurally very
      similar carotenoids. The database reported can be used for applications in
      geobiology and exobiology for the detection of pigment signals in natural
      settings. 

PMID- 25368349
TI  - Biomarkers and their Raman spectroscopic signatures: a spectral challenge for
      analytical astrobiology.
AB  - The remote robotic exploration of extraterrestrial scenarios for evidence of
      biological colonization in 'search for life' missions using Raman spectroscopy is
      critically dependent on two major factors: firstly, the Raman spectral
      recognition of characteristic biochemical spectral signatures in the presence of
      mineral matrix features; and secondly, the positive unambiguous identification of
      molecular biomaterials which are indicative of extinct or extant life. Both of
      these factors are considered here: the most important criterion is the clear
      definition of which biochemicals truly represent biomarkers, whose presence in
      the planetary geological record from an analytical astrobiological standpoint
      will unambiguously be indicative of life as recognized from its remote
      instrumental interrogation. Also discussed in this paper are chemical compounds
      which are associated with living systems, including biominerals, which may not in
      themselves be definitive signatures of life processes and origins but whose
      presence provides an indicator of potential life-bearing matrices. 

PMID- 25368350
TI  - Raman spectroscopy on Mars: identification of geological and bio-geological
      signatures in Martian analogues using miniaturized Raman spectrometers.
AB  - The first Raman spectrometers to be used for in situ analysis of planetary
      material will be launched as part of powerful, rover-based analytical
      laboratories within the next 6 years. There are a number of significant
      challenges associated with building spectrometers for space applications,
      including limited volume, power and mass budgets, the need to operate in harsh
      environments and the need to operate independently and intelligently for long
      periods of time (due to communication limitations). Here, we give an overview of
      the technical capabilities of the Raman instruments planned for future planetary
      missions and give a review of the preparatory work being pursued to ensure that
      such instruments are operated successfully and optimally. This includes analysis
      of extremophile samples containing pigments associated with biological processes,
      synthetic materials which incorporate biological material within a mineral
      matrix, planetary analogues containing low levels of reduced carbon and samples
      coated with desert varnish that incorporate both geo-markers and biomarkers. We
      discuss the scientific importance of each sample type and the challenges using
      portable/flight-prototype instrumentation. We also report on technical
      development work undertaken to enable the next generation of Raman instruments to
      reach higher levels of sensitivity and operational efficiency. 

PMID- 25368351
TI  - Conjugated polyenes as chemical probes of life signature: use of Raman
      spectroscopy to differentiate polyenic pigments.
AB  - Polyenes, which are represented by carotenes, carotenoids and conjugated
      polyenals, are some of the most important targets for astrobiology, because they
      can provide strong evidence of the presence of organic compounds in the most
      extreme environments, such as on Mars. Raman spectroscopy has been used as the
      main analytical tool in the identification of such compounds, for the greatest
      variety of living species, from microorganisms to animals and plants. However,
      using only the position of the characteristic Raman bands can lead to errors in
      tentatively identifying chemicals. In this work, we present a series of
      observations that can provide a more complete and robust way to analyse the Raman
      spectrum of a polyenal, in which the position, the intensity, the use of various
      laser lines for excitation, and the combination of more than one pigment can be
      considered in the complete analysis. 

PMID- 25368352
TI  - Raman spectroscopy meets extremophiles on Earth and Mars: studies for successful
      search of life.

PMID- 25368353
TI  - Raman spectroscopic fingerprints of scytonemin-imine: density functional theory
      calculations of a novel potential biomarker.
AB  - Scytonemin-imine, a novel derivative of scytonemin, has been isolated and
      identified very recently and proposed to serve as a photoprotective biomarker for
      certain bacteria growing under intense photon flux density. This study predicts
      theoretically the Raman spectrum of scytonemin-imine by density functional theory
      calculations and provides comparison of major bands to those of scytonemin, the
      parent compound for which both the experimentally characterized and theoretically
      predicted spectra exist in the literature. It is proposed to be an addendum to
      the collection of our previous work on scytonamin and its derivatives to
      facilitate recognition of the diagnostic Raman spectral signatures for scytonemin
      imine. 

PMID- 25368355
TI  - Mobile Raman spectroscopy in astrobiology research.
AB  - Raman spectroscopy has proved to be a very useful technique in astrobiology
      research. Especially, working with mobile instrumentation during fieldwork can
      provide useful experiences in this field. In this work, we provide an overview of
      some important aspects of this research and, apart from defining different types
      of mobile Raman spectrometers, we highlight different reasons for this research.
      These include gathering experience and testing of mobile instruments, the
      selection of target molecules and to develop optimal data processing techniques
      for the identification of the spectra. We also identify the analytical techniques
      that it would be most appropriate to combine with Raman spectroscopy to maximize
      the obtained information and the synergy that exists with Raman spectroscopy
      research in other research areas, such as archaeometry and forensics.

PMID- 25368354
TI  - Detection of pigments of halophilic endoliths from gypsum: Raman portable
      instrument and European Space Agency's prototype analysis.
AB  - A prototype instrument, under development at the University of Leicester, for the
      future European Space Agency (ESA) ExoMars mission, was used for the analysis of
      microbial pigments within a stratified gypsum crust from a hypersaline saltern
      evaporation pond at Eilat (Israel). Additionally, the same samples were analysed
      using a miniaturized Raman spectrometer, featuring the same 532 nm excitation.
      The differences in the position of the specific bands, attributed to carotenoid
      pigments from different coloured layers, were minor when analysed by the ESA
      prototype instrument; therefore, making it difficult to distinguish among the
      different pigments. The portable Delta Nu Advantage instrument allowed for the
      discrimination of microbial carotenoids from the orange/green and purple layers.
      The purpose of this study was to complement previous laboratory results with new
      data and experience with portable or handheld Raman systems, even with a
      dedicated prototype Raman system for the exploration of Mars. The latter is
      equipped with an excitation wavelength falling within the carotenoid polyene
      resonance region. The ESA prototype Raman instrument detected the carotenoid
      pigments (biomarkers) with ease, although further detailed distinctions among
      them were not achieved. 

PMID- 25368356
TI  - Will-o'-the-Wisp: an ancient mystery with extremophile origins?
AB  - This paper draws a comparison between the 700-year-old historically reported will
      o'-the-wisp phenomenon and the more recent discovery of extremophilic
      colonization of hostile environments; both have been observed as present in
      isolated, stressed environmental regions and originating from biological
      phenomena. However, whereas extremophilic activity can be understood in terms of
      a survival strategy based upon the synthesis of specific suites of protective
      biochemicals which are designed to control biogeologically the stressed habitats
      and to provide protection against the extreme environments, the analytical
      techniques that have proved so successful for the illumination of these survival
      strategies of extremophiles and which are now being miniaturized for in-field
      studies and for extraterrestrial exploration have not been applied to a
      clarification or evaluation of the phenomenon of will-o'-the-wisp. The reason is
      simply that the will-o'-the-wispsightings have now disappeared completely.
      Tantalizingly, all of the most reasonable physico-chemical and biological
      explanations for the will-o'-the-wisp phenomenon proved to be unsatisfactory in
      some respect and it is clear that, just as in the case of extremophilic
      colonization, will-o'-the-wisp would benefit from a modern rigorous analytical
      study which would produce the data from which the potentially novel biological
      behaviour could be characterized and which would help a better understanding to
      be made of our natural world.

PMID- 25368357
TI  - Carving bipolarity using a lithium sword.
AB  - The classification of mood disorders lacks precision and consequently there has
      been no recent meaningful advance in their treatment. By virtue of its
      therapeutic specificity, lithium responsivity offers an opportunity to diagnose a
      definitive subtype of mood disorders that may provide a platform for the
      development of targeted therapy. 

PMID- 25368358
TI  - Low birth weight, preterm birth and small for gestational age association with
      adult depression: systematic review and meta-analysis.
AB  - BACKGROUND: There is no consensus on the effects that low birth weight, premature
      birth and intrauterine growth have on later depression. AIMS: To review
      systematically the evidence on the relationship of low birth weight, smallness
      for gestational age (SGA) and premature birth with adult depression. METHOD: We
      searched the literature for original studies assessing the effect of low birth
      weight, premature birth and SGA on adult depression. Separate meta-analyses were
      carried out for each exposure using random and fixed effects models. We evaluated
      the contribution of methodological covariates to heterogeneity using meta
      regression. RESULTS: We identified 14 studies evaluating low birth weight, 9
      premature birth and 4 SGA. Low birth weight increased the odds of depression (OR
      = 1.39, 95% CI 1.21-1.60). Premature birth and SGA were not associated with
      depression, but publication bias might have underestimated the effect of the
      former and only four studies evaluated SGA. CONCLUSIONS: Low birth weight was
      associated with depression. Future studies evaluating premature birth and SGA are
      needed.

PMID- 25368359
TI  - Height in relation to dementia death: individual participant meta-analysis of 18
      UK prospective cohort studies.
AB  - BACKGROUND: That risk factors measured in middle age may not fully explain future
      dementia risk implicates exposures acting earlier in life. Height may capture
      early-life illness, adversity, nutrition and psychosocial stress. AIMS: To
      investigate the little-explored association between height and dementia death.
      Method Individual participant meta-analysis using 18 prospective general
      population cohort studies with identical methodologies (1994-2008; n = 181 800).
      RESULTS: Mean follow-up of 9.8 years gave rise to 426 and 667 dementia deaths in
      men and women respectively. The mean heights were 174.4 cm (s.d. = 7.3) for men
      and 161.0 cm (s.d. = 6.8) for women. In analyses taking into account multiple
      covariates, increasing height was related to lower rates of death from dementia
      in a dose-response pattern (P ? 0.01 for trend). There was evidence of a
      differential effect by gender (P = 0.016 for interaction). Thus, the association
      observed in men (hazard ratio per s.d. decrease in height 1.24, 95% CI 1.11-1.39)
      was markedly stronger than that apparent in women (HR = 1.13, 95% CI 1.03-1.24).
      CONCLUSIONS: Early-life circumstances, indexed by adult height, may influence
      later dementia risk.

PMID- 25368360
TI  - Use of the first-person pronoun in schizophrenia.

PMID- 25368361
TI  - Authors' reply.

PMID- 25368362
TI  - BDNF and proBDNF as biomarkers for bipolar disorder.

PMID- 25368363
TI  - Authors' reply.

PMID- 25368364
TI  - Early and delayed treatment of bipolar disorder.

PMID- 25368365
TI  - Authors' reply.

PMID- 25368366
TI  - 'Reasonable adjustments' for vulnerable patients.

PMID- 25368367
TI  - Authors' reply.

PMID- 25368370
TI  - Can pain and function be distinguished in the Oxford Hip Score in a meaningful
      way? : an exploratory and confirmatory factor analysis.
AB  - OBJECTIVE: The objective of this study was to explore dimensionality of the
      Oxford Hip Score (OHS) and examine whether self-reported pain and functioning can
      be distinguished in the form of subscales. METHODS: This was a secondary data
      analysis of the UK NHS hospital episode statistics/patient-reported outcome
      measures dataset containing pre-operative OHS scores on 97 487 patients who were
      undergoing hip replacement surgery. RESULTS: The proposed number of factors to
      extract depended on the method of extraction employed. Velicer's Minimum Average
      Partial test and the Parallel Analysis suggested one factor, the Cattell's scree
      test and Kaiser-over-1 rule suggested two factors. Exploratory factor analysis
      demonstrated that the two-factor OHS had most of the items saliently loading
      either of the two factors. These factors were named 'Pain' and 'Function' and
      their respective subscales were created. There was some cross-loading of items: 8
      (pain on standing up from a chair) and 11 (pain during work). These items were
      assigned to the 'Pain' subscale. The final 'Pain' subscale consisted of items 1,
      8, 9, 10, 11 and 12. The 'Function' subscale consisted of items 2, 3, 4, 5, 6 and
      7, with the recommended scoring of the subscales being from 0 (worst) to 100
      (best). Cronbach's alpha was 0.855 for the 'Pain' subscale and 0.861 for the
      'Function' subscale. A confirmatory factor analysis demonstrated that the two
      factor model of the OHS had a better fit. However, none of the one-factor or two
      factor models was rejected. CONCLUSION: Factor analyses demonstrated that, in
      addition to current usage as a single summary scale, separate information on pain
      and self-reported function can be extracted from the OHS in a meaningful way in
      the form of subscales. Cite this article: Bone Joint Res 2014;3:305-9.

PMID- 25368371
TI  - Fronto-striatal dysfunction during reward processing in unaffected siblings of
      schizophrenia patients.
AB  - Schizophrenia is a psychiatric disorder that is associated with impaired
      functioning of the fronto-striatal network, in particular during reward
      processing. However, it is unclear whether this dysfunction is related to the
      illness itself or whether it reflects a genetic vulnerability to develop
      schizophrenia. Here, we examined reward processing in unaffected siblings of
      schizophrenia patients using functional magnetic resonance imaging. Brain
      activity was measured during reward anticipation and reward outcome in 27
      unaffected siblings of schizophrenia patients and 29 healthy volunteers using a
      modified monetary incentive delay task. Task performance was manipulated online
      so that all subjects won the same amount of money. Despite equal performance,
      siblings showed reduced activation in the ventral striatum, insula, and
      supplementary motor area (SMA) during reward anticipation compared to controls.
      Decreased ventral striatal activation in siblings was correlated with sub
      clinical negative symptoms. During the outcome of reward, siblings showed
      increased activation in the ventral striatum and orbitofrontal cortex compared to
      controls. Our finding of decreased activity in the ventral striatum during reward
      anticipation and increased activity in this region during receiving reward may
      indicate impaired cue processing in siblings. This is consistent with the notion
      of dopamine dysfunction typically associated with schizophrenia. Since unaffected
      siblings share on average 50% of their genes with their ill relatives, these
      deficits may be related to the genetic vulnerability for schizophrenia. 

PMID- 25368372
TI  - Rasagiline in the Treatment of the Persistent Negative Symptoms of Schizophrenia.
AB  - OBJECTIVE: The current study examined the efficacy and safety of rasagiline, a
      selective MAO-B inhibitor, for the treatment of persistent negative symptoms.
      METHODS: Sixty people with Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, schizophrenia or schizoaffective disorder, who met a priori
      criteria for persistent negative symptoms, were randomized to receive rasagiline,
      1mg/d (n = 31) or placebo (n = 29) in a 12-week, double-blind, placebo-controlled
      clinical trial. The Scale for the Assessment of Negative Symptoms (SANS) total
      score was used to assess change in negative symptoms. The Repeatable Battery for
      the Assessment of Neuropsychological Status (RBANS), N-Back test, a probabilistic
      learning task, and a delayed discounting task were used to assess cognition.
      RESULTS: In a mixed model analysis of covariance (MM-ANCOVA), with time as a
      continuous variable, there was a significant treatment * time effect for SANS
      total score (F = 5.61(df = 1,40.3), P = .023). The treatment * time interaction
      effect was also significant for the SANS avolition subscale score (F(1,40.2) =
      10.41, P = .002). In a post hoc MM-ANCOVA analyses, with time as a categorical
      variable, group differences were significant at week 12 for SANS total score
      (t(37.3) = 2.15; P = .04; d = -0.41) and SANS avolition subscale score (t(49.0) =
      3.06; P = .004; d = -0.46). There was a significant difference in number of
      participants with a >=20% reduction in SANS avolition score (chi(2)(1) = 10.94; P
      = .0009), but not in SANS total score (chi(2)(1) = 1.11; P = .29). There were no
      significant group differences on the RBANS, N-Back, probabilistic learning, or
      delayed discounting tasks. CONCLUSIONS: Study results support future studies of
      the utility of rasagiline for the treatment of negative symptoms, including
      avolition (clinicaltrials.gov trial number: NCT00492336).

PMID- 25368374
TI  - MCL-1 but not BCL-XL is critical for the development and sustained expansion of
      thymic lymphoma in p53-deficient mice.
AB  - Apoptosis plays a role in normal lymphopoiesis and lymphoid malignancies. Pro
      survival MCL-1 is essential for survival of T-cell progenitors, BCL-XL for
      immature thymocytes, and BCL-2 for mature T cells. Conversely, little is known
      about the regulators that are required for the survival of T-cell lymphomas. We
      used constitutive and conditionally gene-targeted mice to investigate which pro
      survival BCL-2 family member is required for the sustained survival of thymic
      lymphomas initiated by loss of p53. Constitutive loss of a single Mcl-1 allele
      delayed tumor onset. In contrast, lymphomas emerging in p53(-/-) mice in which
      Mcl-1 could be conditionally deleted had been selected for retention of MCL-1
      expression. In contrast, complete loss of BCL-XL had no impact on lymphoma
      development in p53(-/-) mice. These results demonstrate that thymic lymphomas
      elicited by loss of p53 must arise from cancer-initiating cells that require MCL
      1 for their survival. Acute deletion of both Mcl-1 alleles abrogated the
      expansion of p53(-/-) lymphomas in mice, whereas inducible loss of BCL-XL had
      little impact. This reveals that MCL-1 is essential for the sustained survival of
      these malignant cells and suggests that targeting MCL-1 may be an attractive
      strategy for the treatment of T-cell lymphoma. 

PMID- 25368373
TI  - Extracellular nicotinamide phosphoribosyltransferase (NAMPT) promotes M2
      macrophage polarization in chronic lymphocytic leukemia.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in
      nicotinamide adenine dinucleotide biosynthesis. In the extracellular compartment,
      it exhibits cytokine-/adipokinelike properties, suggesting that it stands at the
      crossroad between metabolism and inflammation. Here we show that both
      intracellular and extracellular NAMPT levels are increased in cells and plasma of
      chronic lymphocytic leukemia (CLL) patients. The extracellular form (eNAMPT) is
      produced by CLL lymphocytes upon B-cell receptor, Toll-like receptor, and nuclear
      factor kappaB (NF-kappaB) signaling pathway activation. eNAMPT is important for
      differentiation of resting monocytes, polarizing them toward tumor-supporting M2
      macrophages. These cells express high levels of CD163, CD206, and indoleamine 2,3
      dioxygenase and secrete immunosuppressive (interleukin [IL] 10, CC chemokine
      ligand 18) and tumor-promoting (IL-6, IL-8) cytokines. NAMPT-primed M2
      macrophages activate extracellular-regulated kinase 1/2, signal transducer and
      activator of transcription 3, and NF-kappaB signaling; promote leukemic cell
      survival; and reduce T-cell responses. These effects are independent of the
      enzymatic activity of NAMPT, as inferred from the use of an enzymatically
      inactive mutant. Overall, these results reveal that eNAMPT is a critical element
      in the induction of an immunosuppressive and tumor-promoting microenvironment of
      CLL.

PMID- 25368375
TI  - The impact of genomics on public health practice.
AB  - INTRODUCTION: Genomic science is developing rapidly, and engagement of public
      health professionals will be necessary to appraise new technologies and use them
      effectively. SOURCES OF DATA: We use established domains of public health and
      draw on the literature and expert knowledge to illustrate how genomic
      technologies give rise to new applications. AREAS OF AGREEMENT: Genomic
      technologies are useful in rare inherited disease, including population screening
      programmes, in health care and for surveillance, diagnosis and treatment of
      infectious disease. AREAS OF CONTROVERSY: It is less clear when and how genetic
      susceptibility testing will be used for common chronic disease prevention or
      protection from environmental hazards. GROWING POINTS: Developments in public
      health practice will be necessary to ensure rapid and effective implementation of
      genomic science. AREAS TIMELY FOR DEVELOPING RESEARCH: Public health researchers
      should address how to accelerate the implementation of genomics for health
      benefit in developed and developing countries.

PMID- 25368376
TI  - NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells:
      A Technology Designed for Orthopedic Regenerative Medicine.
AB  - Human bone marrow-derived stromal/stem cells (BMSCs) have great therapeutic
      potential for treating skeletal disease and facilitating skeletal repair,
      although maintaining their multipotency and expanding these cells ex vivo have
      proven difficult. Because most stem cell-based applications to skeletal
      regeneration and repair in the clinic would require large numbers of functional
      BMSCs, recent research has focused on methods for the appropriate selection,
      expansion, and maintenance of BMSC populations during long-term culture. We
      describe here a novel biological method that entails selection of human BMSCs
      based on NOTCH2 expression and activation of the NOTCH signaling pathway in
      cultured BMSCs via a tissue culture plate coated with recombinant human JAGGED1
      (JAG1) ligand. We demonstrate that transient JAG1-mediated NOTCH signaling
      promotes human BMSC maintenance and expansion while increasing their skeletogenic
      differentiation capacity, both ex vivo and in vivo. This study is the first of
      its kind to describe a NOTCH-mediated methodology for the maintenance and
      expansion of human BMSCs and will serve as a platform for future clinical or
      translational studies aimed at skeletal regeneration and repair. 

PMID- 25368377
TI  - Concise review: modeling central nervous system diseases using induced
      pluripotent stem cells.
AB  - Induced pluripotent stem cells (iPSCs) offer an opportunity to delve into the
      mechanisms underlying development while also affording the potential to take
      advantage of a number of naturally occurring mutations that contribute to either
      disease susceptibility or resistance. Just as with any new field, several models
      of screening are being explored, and innovators are working on the most efficient
      methods to overcome the inherent limitations of primary cell screens using iPSCs.
      In the present review, we provide a background regarding why iPSCs represent a
      paradigm shift for central nervous system (CNS) disease modeling. We describe the
      efforts in the field to develop more biologically relevant CNS disease models,
      which should provide screening assays useful for the pharmaceutical industry. We
      also provide some examples of successful uses for iPSC-based screens and suggest
      that additional development could revolutionize the field of drug discovery. The
      development and implementation of these advanced iPSC-based screens will create a
      more efficient disease-specific process underpinned by the biological mechanism
      in a patient- and disease-specific manner rather than by trial-and-error.
      Moreover, with careful and strategic planning, shared resources can be developed
      that will enable exponential advances in the field. This will undoubtedly lead to
      more sensitive and accurate screens for early diagnosis and allow the
      identification of patient-specific therapies, thus, paving the way to
      personalized medicine. 

PMID- 25368378
TI  - Osteogenic differentiation of human amniotic epithelial cells and its application
      in alveolar defect restoration.
AB  - The present study investigated the detailed in vitro osteogenic differentiation
      process and in vivo bone regenerative property of human amniotic epithelial cells
      (hAECs). The in vitro osteogenic differentiation process of hAECs was evaluated
      by biochemical staining, real-time polymerase chain reaction, and
      immunofluorescence. Next, beta-tricalcium phosphate (beta-TCP) scaffolds alone or
      loaded with hAECs were implanted into the alveolar defects of rats. Micro
      computed tomography evaluation and histologic studies were conducted. Our results
      validated the in vitro osteogenic capacity of hAECs by upregulation of Runx2,
      osterix, alkaline phosphatase, collagen I, and osteopontin, with positive
      biochemical staining for osteoblasts. An epithelial-mesenchymal transformation
      process might be involved in the osteogenic differentiation of hAECs by increased
      expression of transforming growth factor-beta1. Our data also demonstrated that
      in vivo implantation of hAECs loaded on beta-TCP scaffolds, not only improved
      bone regeneration by direct participation, but also reduced the early host immune
      response to the scaffolds. The presented data indicate that hAECs possess proper
      osteogenic differentiation potential and a modulatory influence on the early
      tissue remodeling process, making these cells a potential source of progenitor
      cells for clinical restoration of the alveolar defect. 

PMID- 25368379
TI  - The RASSF1A tumor suppressor regulates XPA-mediated DNA repair.
AB  - RASSF1A may be the most frequently inactivated tumor suppressor identified in
      human cancer so far. It is a proapoptotic Ras effector and plays an important
      role in the apoptotic DNA damage response (DDR). We now show that in addition to
      DDR regulation, RASSF1A also plays a key role in the DNA repair process itself.
      We show that RASSF1A forms a DNA damage-regulated complex with the key DNA repair
      protein xeroderma pigmentosum A (XPA). XPA requires RASSF1A to exert full repair
      activity, and RASSF1A-deficient cells exhibit an impaired ability to repair DNA.
      Moreover, a cancer-associated RASSF1A single-nucleotide polymorphism (SNP)
      variant exhibits differential XPA binding and inhibits DNA repair. The
      interaction of XPA with other components of the repair complex, such as
      replication protein A (RPA), is controlled in part by a dynamic
      acetylation/deacetylation cycle. We found that RASSF1A and its SNP variant
      differentially regulate XPA protein acetylation, and the SNP variant
      hyperstabilizes the XPA-RPA70 complex. Thus, we identify two novel functions for
      RASSF1A in the control of DNA repair and protein acetylation. As RASSF1A
      modulates both apoptotic DDR and DNA repair, it may play an important and
      unanticipated role in coordinating the balance between repair and death after DNA
      damage. 

PMID- 25368380
TI  - The major myelin-resident protein PLP is transported to myelin membranes via a
      transcytotic mechanism: involvement of sulfatide.
AB  - Myelin membranes are sheet-like extensions of oligodendrocytes that can be
      considered membrane domains distinct from the cell's plasma membrane. Consistent
      with the polarized nature of oligodendrocytes, we demonstrate that transcytotic
      transport of the major myelin-resident protein proteolipid protein (PLP) is a key
      element in the mechanism of myelin assembly. Upon biosynthesis, PLP traffics to
      myelin membranes via syntaxin 3-mediated docking at the apical-surface-like cell
      body plasma membrane, which is followed by subsequent internalization and
      transport to the basolateral-surface-like myelin sheet. Pulse-chase experiments,
      in conjunction with surface biotinylation and organelle fractionation, reveal
      that following biosynthesis, PLP is transported to the cell body surface in
      Triton X-100 (TX-100)-resistant microdomains. At the plasma membrane, PLP
      transiently resides within these microdomains and its lateral dissipation is
      followed by segregation into 3-[(3-cholamidopropyl)-dimethylammonio]-1
      propanesulfonate (CHAPS)-resistant domains, internalization, and subsequent
      transport toward the myelin membrane. Sulfatide triggers PLP's reallocation from
      TX-100- into CHAPS-resistant membrane domains, while inhibition of sulfatide
      biosynthesis inhibits transcytotic PLP transport. Taking these findings together,
      we propose a model in which PLP transport to the myelin membrane proceeds via a
      transcytotic mechanism mediated by sulfatide and characterized by a
      conformational alteration and dynamic, i.e., transient, partitioning of PLP into
      distinct membrane microdomains involved in biosynthetic and transcytotic
      transport. 

PMID- 25368381
TI  - Loss of BRMS1 promotes a mesenchymal phenotype through NF-kappaB-dependent
      regulation of Twist1.
AB  - Breast cancer metastasis suppressor 1 (BRMS1) is downregulated in non-small cell
      lung cancer (NSCLC), and its reduction correlates with disease progression.
      Herein, we investigate the mechanisms through which loss of the BRMS1 gene
      contributes to epithelial-to-mesenchymal transition (EMT). Using a short hairpin
      RNA (shRNA) system, we show that loss of BRMS1 promotes basal and transforming
      growth factor beta-induced EMT in NSCLC cells. NSCLC cells expressing BRMS1
      shRNAs (BRMS1 knockdown [BRMS1(KD)]) display mesenchymal characteristics,
      including enhanced cell migration and differential regulation of the EMT markers.
      Mesenchymal phenotypes observed in BRMS1(KD) cells are dependent on RelA/p65, the
      transcriptionally active subunit of nuclear factor kappa B (NF-kappaB). In
      addition, chromatin immunoprecipitation analysis demonstrates that loss of BRMS1
      increases Twist1 promoter occupancy of RelA/p65 K310-a key histone modification
      associated with increased transcription. Knockdown of Twist1 results in reversal
      of BRMS1(KD)-mediated EMT phenotypic changes. Moreover, in our animal model,
      BRMS1(KD)/Twist1(KD) double knockdown cells were less efficient in establishing
      lung tumors than BRMS1(KD) cells. Collectively, this study demonstrates that loss
      of BRMS1 promotes malignant phenotypes that are dependent on NF-kappaB-dependent
      regulation of Twist1. These observations offer fresh insight into the mechanisms
      through which BRMS1 regulates the development of metastases in NSCLC. 

PMID- 25368382
TI  - The basic leucine zipper stress response regulator Yap5 senses high-iron
      conditions by coordination of [2Fe-2S] clusters.
AB  - Iron is an essential, yet at elevated concentrations toxic trace element. To
      date, the mechanisms of iron sensing by eukaryotic iron-responsive transcription
      factors are poorly understood. The Saccharomyces cerevisiae transcription factor
      Yap5, a member of the Yap family of bZIP stress response regulators,
      administrates the adaptive response to high-iron conditions. Despite the central
      role of the iron-sensing process for cell viability, the molecule perceived by
      Yap5 and the underlying regulatory mechanisms are unknown. Here, we show that
      Yap5 senses high-iron conditions by two Fe/S clusters bound to its activator
      domain (Yap5-AD). The more stable iron-regulatory Fe/S cluster at the N-terminal
      cysteine-rich domain (n-CRD) of Yap5 is detected in vivo and in vitro. The second
      cluster coordinated by the C-terminal CRD can only be shown after chemical
      reconstitution, since it is bound in a labile fashion. Both clusters are of the
      [2Fe-2S] type as characterized by UV/visible (UV/Vis), circular dichroism,
      electron paramagnetic resonance (EPR), and Mossbauer spectroscopy. Fe/S cluster
      binding to Yap5-AD induces a conformational change that may activate
      transcription. The cluster-binding motif of the n-CRD domain is highly conserved
      in HapX-like transcription factors of pathogenic fungi and thus may represent a
      general sensor module common to many eukaryotic stress response regulators. 

PMID- 25368383
TI  - A variably occupied CTCF binding site in the ultrabithorax gene in the Drosophila
      bithorax complex.
AB  - Although the majority of genomic binding sites for the insulator protein CCCTC
      binding factor (CTCF) are constitutively occupied, a subset show variable
      occupancy. Such variable sites provide an opportunity to assess context-specific
      CTCF functions in gene regulation. Here, we have identified a variably occupied
      CTCF site in the Drosophila Ultrabithorax (Ubx) gene. This site is occupied in
      tissues where Ubx is active (third thoracic leg imaginal disc) but is not bound
      in tissues where the Ubx gene is repressed (first thoracic leg imaginal disc).
      Using chromatin conformation capture, we show that this site preferentially
      interacts with the Ubx promoter region in the active state. The site lies close
      to Ubx enhancer elements and is also close to the locations of several gypsy
      transposon insertions that disrupt Ubx expression, leading to the bx mutant
      phenotype. gypsy insertions carry the Su(Hw)-dependent gypsy insulator and were
      found to affect both CTCF binding at the variable site and the chromatin
      topology. This suggests that insertion of the gypsy insulator in this region
      interferes with CTCF function and supports a model for the normal function of the
      variable CTCF site as a chromatin loop facilitator, promoting interaction between
      Ubx enhancers and the Ubx transcription start site. 

PMID- 25368384
TI  - Genome-wide association of mediator and RNA polymerase II in wild-type and
      mediator mutant yeast.
AB  - Mediator is a large, multisubunit complex that is required for essentially all
      mRNA transcription in eukaryotes. In spite of the importance of Mediator, the
      range of its targets and how it is recruited to these is not well understood.
      Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to
      transcriptional activation by two distinct mechanisms, one depending on the tail
      module triad and favoring SAGA-regulated genes, and the second occurring
      independently of the tail module and favoring TFIID-regulated genes. Here, we use
      chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on
      tail module subunits for Mediator recruitment and polymerase II (Pol II)
      association occurs preferentially at SAGA-regulated over TFIID-regulated genes on
      a genome-wide scale. We also show that recruitment of tail module subunits to
      active gene promoters continues genome-wide when Mediator integrity is
      compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular
      nature of the Mediator complex in vivo. In addition, our data indicate that
      promoters exhibiting strong and stable occupancy by Mediator have a wide range of
      activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also
      identify a number of strong Mediator occupancy peaks that overlap dubious open
      reading frames (ORFs) and are likely to include previously unrecognized upstream
      activator sequences. 

PMID- 25368385
TI  - Deregulation of Rb-E2F1 axis causes chromosomal instability by engaging the
      transactivation function of Cdc20-anaphase-promoting complex/cyclosome.
AB  - The E2F family of transcription factors regulates genes involved in various
      aspects of the cell cycle. Beyond the well-documented role in G1/S transition,
      mitotic regulation by E2F has also been reported. Proper mitotic progression is
      monitored by the spindle assembly checkpoint (SAC). The SAC ensures bipolar
      separation of chromosomes and thus prevents aneuploidy. There are limited reports
      on the regulation of the SAC by E2F. Our previous work identified the SAC protein
      Cdc20 as a novel transcriptional regulator of the mitotic ubiquitin carrier
      protein UbcH10. However, none of the Cdc20 transcription complex proteins have
      any known DNA binding domain. Here we show that an E2F1-DP1 heterodimer is
      involved in recruitment of the Cdc20 transcription complex to the UBCH10 promoter
      and in transactivation of the gene. We further show that inactivation of Rb can
      facilitate this transactivation process. Moreover, this E2F1-mediated regulation
      of UbcH10 influences mitotic progression. Deregulation of this pathway results in
      premature anaphase, chromosomal abnormalities, and aneuploidy. We conclude that
      excess E2F1 due to Rb inactivation recruits the complex of Cdc20 and the anaphase
      promoting complex/cyclosome (Cdc20-APC/C) to deregulate the expression of UBCH10,
      leading to chromosomal instability in cancer cells. 

PMID- 25368386
TI  - NF-kappaB signaling is required for XBP1 (unspliced and spliced)-mediated effects
      on antiestrogen responsiveness and cell fate decisions in breast cancer.
AB  - Antiestrogen therapy induces the unfolded protein response (UPR) in estrogen
      receptor-positive (ER(+)) breast cancer. X-box binding protein 1 (XBP1), which
      exists in the transcriptionally inactive unspliced form [XBP1(U)] and the spliced
      active form [XBP1(S)], is a key UPR component mediating antiestrogen resistance.
      We now show a direct link between the XBP1 and NF-kappaB survival pathways in
      driving the cell fate decisions in response to antiestrogens in ER(+) breast
      cancer cells, both in vitro and in a xenograft mouse model. Using novel spliced
      and nonspliceable forms of XBP1, we show that XBP1(U) functions beyond being a
      dominant negative of XBP1(S). Both isoforms regulate NF-kappaB activity via
      ERalpha; XBP1(S) is more potent because it also directly regulates p65/RelA
      expression. These findings provide new insights into the fundamental signaling
      activities of spliced and unspliced XBP1 in breast cancer, establish NF-kappaB to
      be a mediator of these activities, and identify XBP1 and its splicing to be novel
      therapeutic targets. 

PMID- 25368388
TI  - Don't use antipsychotics routinely to treat agitation and aggression in people
      with dementia.

PMID- 25368387
TI  - DGCR14 induces Il17a gene expression through the RORgamma/BAZ1B/RSKS2 complex.
AB  - The Dgcr14/Es2 gene is located in a chromosomal region the loss of which has been
      associated with DiGeorge syndrome, a cause of immunodeficiency, heart defects,
      and skeletal abnormalities. However, the role of DGCR14 protein remains to be
      elucidated. Here, I found that DGCR14 protein acts as a coactivator of RORgammat
      in TH17 cells. Biochemical purification of the RORgamma coregulator complex
      allowed me to identify the associated DGCR14 protein by matrix-assisted laser
      desorption ionization-time of flight mass spectrometry. Overexpression of Dgcr14
      mRNA enhanced RORgammat-mediated transcriptional activity and facilitated TH17
      cell differentiation. Furthermore, knockdown of Dgcr14 reduced Il17a mRNA
      expression. I also found that DGCR14 associated with ribosomal S6 kinase 2 (RSK2,
      also called RpS6ka3) and BAZ1B, both of which were recruited to the Il17a
      promoter during TH17 cell differentiation. Knockdown of Baz1b or RpS6ka3 also
      reduced Il17a mRNA expression, and Baz1b knockdown increased transcriptional
      suppressive histone marks (histone H3K9me3) on the Il17a promoter. My findings
      showed the roles of DGCR14, RSK2, and BAZ1B in the transcriptional regulation of
      Il17a mRNA during TH17 cell differentiation. 

PMID- 25368389
TI  - Indian government outlines plan to try to eliminate tuberculosis by 2020.

PMID- 25368390
TI  - Maine judge refuses to quarantine nurse who cared for Ebola patients.

PMID- 25368392
TI  - Research papers should omit their authors' affiliations.

PMID- 25368391
TI  - WHO reports decline in number of new Ebola cases in Liberia.

PMID- 25368394
TI  - Cancer research in Asian American, Native Hawaiian, and Pacific Islander
      populations: accelerating cancer knowledge by acknowledging and leveraging
      heterogeneity.
AB  - The Asian American, Native Hawaiian, and Pacific Islander population is large,
      growing, and extremely heterogeneous. Not only do they bear unique burdens of
      incidence and outcomes for certain cancer types, they exhibit substantial
      variability in cancer incidence and survival patterns across the ethnic groups.
      By acknowledging and leveraging this heterogeneity through investing in cancer
      research within these populations, we have a unique opportunity to accelerate the
      availability of useful and impactful cancer knowledge. See all the articles in
      this CEBP Focus section, "Cancer in Asian and Pacific Islander Populations."

PMID- 25368395
TI  - Cancer in Asian American and Pacific Islander populations: linking research and
      policy to identify and reduce disparities.

PMID- 25368396
TI  - Patient and provider characteristics associated with colorectal, breast, and
      cervical cancer screening among Asian Americans.
AB  - BACKGROUND: Routinely recommended screening for breast, cervical, and colorectal
      cancers can significantly reduce mortality from these types of cancer, yet
      screening is underutilized among Asians. Surveys rely on self-report and often
      are underpowered for analysis by Asian ethnicities. Electronic health records
      (EHR) include validated (as opposed to recall-based) rates of cancer screening.
      In this article, we seek to better understand cancer screening patterns in a
      population of insured Asian Americans. METHODS: We calculated rates of compliance
      with cervical, breast, and colorectal cancer screening among Asians from an EHR
      population and compared them with non-Hispanic whites. We performed multivariable
      modeling to evaluate potential predictors (at the provider- and patient-level) of
      screening completion among Asian patients. RESULTS: Aggregation of Asian
      subgroups masked heterogeneity in screening rates. Asian Indians and native
      Hawaiians and Pacific Islanders had the lowest rates of screening in our sample,
      well below that of non-Hispanic whites. In multivariable analyses, screening
      completion was negatively associated with patient-physician language discordance
      for mammography [OR, 0.81; 95% confidence interval (CI), 0.71-0.92] and
      colorectal cancer screening (OR, 0.79; CI, 0.72-0.87) and positively associated
      with patient-provider gender concordance for mammography (OR, 1.16; CI, 1.00
      1.34) and cervical cancer screening (OR, 1.66; CI, 1.51-1.82). In addition,
      patient enrollment in online health services increased mammography (OR, 1.32; CI,
      1.20-1.46) and cervical cancer screening (OR, 1.31; CI, 1.24-1.37). CONCLUSIONS:
      Language- and gender-concordant primary care providers and culturally tailored
      online health resources may help improve preventive cancer screening in Asian
      patient populations. IMPACT: This study demonstrates how the use of EHR data can
      inform investigations of primary prevention practices within the healthcare
      delivery setting.

PMID- 25368397
TI  - Disaggregating data on Asian American and Pacific Islander women to provide new
      insights on potential exposures to hazardous air pollutants in California.
AB  - BACKGROUND: The Asian American and Pacific Islander (AAPI) population is
      heterogeneous and rapidly growing in the United States, with a high proportion
      concentrated in California. Although traditionally assumed to have lower rates of
      breast cancer than non-Hispanic white women, recent studies have suggested
      considerable variation in incidence by AAPI ethnic group, with rates in some
      exceeding those in non-Hispanic whites. The potential role of environmental
      toxicants has not been well explored and may provide insights into these
      patterns. METHODS: We created an exposure potential index (EPI) score for 24
      hazardous air pollutants modeled by the U.S. Environmental Protection Agency
      National-Scale Air Toxics Assessment considered to be mammary gland carcinogens,
      and compared values at the census tract level for "geographically concentrated"
      AAPI groups throughout the State. "Geographically concentrated" populations were
      defined as census tracts with at least 100 individuals from a specified
      racial/ethnic population as enumerated by the 2000 Census. RESULTS: Although EPI
      scores differed little between census tracts with aggregated AAPI (mean EPI =
      0.53) and non-Hispanic white women (mean EPI = 0.63), there was substantial
      variation between tracts for disaggregated AAPI groups, with notably higher EPI
      scores for tracts enumerated for Korean or Japanese women (mean EPI of 0.78 and
      0.77, respectively) compared with other AAPI groups. CONCLUSIONS: Our findings
      underscore the importance of disaggregating data for the heterogeneous AAPI
      population to identify differences in potential environmental exposures across
      groups. IMPACT: Future cancer etiology studies should examine environmental
      exposure differences within and across groups for the diverse AAPI population.

PMID- 25368399
TI  - 1,3-Butadiene exposure and metabolism among Japanese American, Native Hawaiian,
      and White smokers.
AB  - BACKGROUND: We hypothesize that the differences in lung cancer risk in Native
      Hawaiians, whites, and Japanese Americans may, in part, be due to variation in
      the metabolism of 1,3-butadiene, one of the most abundant carcinogens in
      cigarette smoke. METHODS: We measured two biomarkers of 1,3-butadiene exposure,
      monohydroxybutyl mercapturic acid (MHBMA) and dihydroxybutyl mercapturic acid
      (DHBMA), in overnight urine samples among 584 Native Hawaiians, Japanese
      Americans, and white smokers in Hawaii. These values were normalized to
      creatinine levels. Ethnic-specific geometric means were compared adjusting for
      age at urine collection, sex, body mass index, and nicotine equivalents (a marker
      of total nicotine uptake). RESULTS: We found that mean urinary MHBMA differed by
      race/ethnicity (P = 0.0002). The values were highest in whites and lowest in
      Japanese Americans. This difference was only observed in individuals with the
      GSTT1-null genotype (P = 0.0001). No difference across race/ethnicity was found
      among those with at least one copy of the GSTT1 gene (P >= 0.72). Mean urinary
      DHBMA did not differ across racial/ethnic groups. CONCLUSIONS: The difference in
      urinary MHBMA excretion levels from cigarette smoking across three ethnic groups
      is, in part, explained by the GSTT1 genotype. Mean urinary MHBMA levels are
      higher in whites among GSTT1-null smokers. IMPACT: The overall higher excretion
      levels of MHBMA in whites and lower levels of MHBMA in Japanese Americans are
      consistent with the higher lung cancer risk in the former. However, the excretion
      levels of MHBMA in Native Hawaiians are not consistent with their disease risk
      and thus unlikely to explain their high risk of lung cancer.

PMID- 25368398
TI  - Chronic hepatitis B and liver cancer risks among Asian immigrants in New York
      City: Results from a large, community-based screening, evaluation, and treatment
      program.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection, the predominant cause of
      hepatocellular carcinoma (HCC) worldwide, disproportionately affects Asian
      Americans. Limited data exist on the variability and characteristics of infection
      that determine disease progression risk within U.S. Asian ethnic subgroups.
      METHODS: Retrospective analyses were conducted on a large, community-based HBV
      screening and treatment program in New York City (NYC). From 2004 to 2008, the
      program enrolled 7,272 Asian-born individuals. Determinants of HBV seroprevalence
      were calculated and risk factors for HCC progression were compared across Asian
      subgroups. RESULTS: Among newly tested individuals, 13% were HBV positive.
      Seroprevalence varied significantly with age, gender, education, birthplace, and
      family history of infection. Chinese-born individuals, particularly from the
      Fujian province, had the highest seroprevalence (23.2% and 33.1%, respectively).
      Clinical and virologic characteristics placed HBV-infected individuals at
      significant risk for HCC. Significant differences in HCC risk existed among Asian
      subgroups in bivariate analysis, including age, gender, HBV viral load, and HBeAg
      status. Differences in HBV genotype and family history of HCC may further HCC
      risk among subgroups. CONCLUSIONS: Asian immigrants in NYC have a high prevalence
      of HBV infection and are at significant risk of disease progression and HCC.
      Although heterogeneity in HBV seroprevalence was found by Asian subgroups, HCC
      risk among infected individuals was primarily explained by age and gender
      differences. Country and province of birth, age, and gender may further explain
      seroprevalence differences. IMPACT: Findings provide estimates of HBV burden in
      Asian ethnic subgroups and identify high-risk groups to target for screening and
      treatment that can prevent HCC.

PMID- 25368400
TI  - Lung cancer incidence trends by histology type among Asian American, Native
      Hawaiian, and Pacific Islander populations in the United States, 1990-2010.
AB  - BACKGROUND: Lung cancer is one of the leading cancer sites diagnosed among Asian
      Americans, Pacific Islanders, and Native Hawaiians (AANHPI). To better understand
      the patterns of lung cancer incidence among AANHPIs, we examined the incidence
      trends of five histologic cell types of lung cancer across ten AANHPI populations
      in comparison with non-Hispanic Whites. METHODS: Lung cancer incidence data from
      1990 through 2010 were obtained from 13 U.S. population-based cancer registries.
      Age-adjusted histologic cell-type-specific incidence rates and 95% confidence
      intervals were calculated. Joinpoint regression models and annual percentage
      change (APC) statistics were used to characterize the magnitude and direction of
      trends. RESULTS: From 1990 through 2010, incidence rates of adenocarcinoma
      increased significantly for Filipino and Korean women with a 2.6% and 3.0% annual
      percentage increase, respectively. More recently, a significant rise in the
      incidence of adenocarcinoma was observed for Chinese men (1996-2010; APC = 1.3%).
      Squamous cell carcinoma (SCC) increased 2.4% per year among Japanese women. For
      SCC, small cell lung carcinoma, large cell and other specified carcinoma, and
      unspecified types, stable or decreasing trends were observed in most AANHPI
      groups and non-Hispanic Whites. CONCLUSIONS: AANHPIs demonstrate a range in the
      burden of lung cancer across histologies and specific populations. IMPACT: These
      findings illustrate the importance of disaggregating AANHPIs into their specific
      populations. The rise in incidence of adenocarcinoma and SCC among certain
      AANHPIs demonstrates the need for research into non-tobacco associated risk
      factors for these populations and targeted efforts for tobacco prevention.

PMID- 25368402
TI  - Cancer death and antihypertensive drug treatment-letter.

PMID- 25368401
TI  - Disaggregated data and beyond: future queries in cancer control research.
AB  - The goal of health equity requires the collection and reporting of disaggregated
      data in underrepresented populations such as Asian American (AA) and Native
      Hawaiian and Other Pacific Islander (NHOPI) communities. A recent Department of
      Health and Human Services report outlines the necessity for disaggregated data,
      which would offer communities, providers, and planners better tools to address
      health problems. In a recent collaboration, the National Cancer Institute (NCI)
      and several registries published a series of articles tracking cancer incidence
      data on AA and NHOPI communities using data from the NCI's Surveillance,
      Epidemiology, and End Results (SEER) program. The findings indicate a need for
      concentrated focus and planning for the next stages of cancer prevention and
      control for AA and NHOPI subpopulations. In this article, we provide (i) the
      context for the perpetuation of the model minority myth as well as historical and
      sociocultural factors that have shaped health and disease for AA and NHOPI
      subgroups; (ii) potential strategies for research and public health policy for AA
      and NHOPI groups using subpopulation-based approaches while addressing challenges
      and limitations; and (iii) a portfolio analysis of currently funded projects
      within the NCI/DCCPS to identify gaps and areas of potential research.

PMID- 25368404
TI  - Temporal trends in thyroid cancer incidence in California-letter.

PMID- 25368403
TI  - Cancer death and antihypertensive drug treatment-response.

PMID- 25368405
TI  - The Cancer Genomics and Epidemiology Navigator: An NCI online tool to enhance
      cancer epidemiology research.

PMID- 25368406
TI  - Accelerometer determined lifestyle behaviors over time-letter.

PMID- 25368407
TI  - Simultaneous Determination of Seven Components from Hawthorn Leaves Flavonoids in
      Rat Plasma by LC-MS/MS.
AB  - In this study, a simple, sensitive, and throughout liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method was developed for the simultaneous
      determination of seven flavonoid compounds, namely, rutin, vitexin-4"-O
      glucoside, vitexin-2"-O-rhamnoside, hyperoside, vitexin, shanyenoside A and
      quercetin in rat plasma after intravenous administration of hawthorn leaves
      flavonoids (HLF) using lysionotin as an internal standard (IS). The target
      compounds were extracted using protein precipitation by methanol. The detection
      was achieved by LC-MS/MS in multiple reaction monitoring mode. The optimal mass
      transition ion pairs (m/z) for quantitation were 609.3/300.1 for rutin,
      593.1/413.2 for vitexin-4"-O-glucoside, 577.3/413.2 for vitexin-2"-O-rhamnoside,
      463.2/300.1 for hyperoside, 431.2/311.2 for vitexin, 407.2/245.1 for shanyenoside
      A, 301.1/151.1 for quercetin and 343.2/313.1 for the IS, respectively. The method
      was fully validated with respect to specificity, sensitivity, linearity,
      precision, accuracy, recovery and stability experiments. A sufficiently sensitive
      and selective LC-MS/MS method was first developed in this study to simultaneously
      evaluate the pharmacokinetics of seven flavonoids in rat plasma following
      intravenous administration of HLF. 

PMID- 25368408
TI  - Development and Validation of a Stability-Indicating RP-UPLC Method for
      Determination of Cloxacillin Sodium in Its Bulk Form and Formulation.
AB  - A simple, linear gradient, rapid, precise and stability-indicating RP-UPLC method
      was developed for the determination of Cloxacillin Sodium in its bulk form and
      formulation. Ultra performance liquid chromatography, a most promising
      advancement in a world of chromatography, reduces analysis time, increases
      reliability through higher resolution, sensitivity and selectivity as well as
      used as an economic method due to reducing solvent consumption. A chromatographic
      separation of a drug as well as its degradants was achieved using Waters acquity
      BEH, 2.1 * 100 mm, 1.7 MUm C18 column with gradient of mobile phase A: phosphate
      buffer, pH 6.8 and mobile phase B: methanol:acetonitrile (75:25). The drug and
      degradants were monitored at a detection wavelength of 225 nm with a flow rate of
      0.35 mL/min and an injection volume of 10 uL. The temperature of the column and
      auto sampler compartments was at 30 degrees C and 25 degrees C +/- 1 degrees C,
      respectively. The retention time of the drug was ~6.9 min. The resolution of the
      drug and degradant peak was >1.5 in all cases. Force degradation of CLOX SOD was
      carried under alkaline, acidic, oxidative, thermal, photo degradation conditions
      and it was analyzed by the proposed method. The drug degrades under alkaline,
      acidic and oxidative conditions but was stable in temperature and light. A
      developed method was validated as per ICH guidelines using validation parameters
      such as precision, linearity and range, limit of quantification, specificity,
      assay and robustness. 

PMID- 25368409
TI  - The proteomics of networks and pathways: a movie is worth a thousand pictures.

PMID- 25368410
TI  - Protectome analysis: a new selective bioinformatics tool for bacterial vaccine
      candidate discovery.
AB  - New generation vaccines are in demand to include only the key antigens sufficient
      to confer protective immunity among the plethora of pathogen molecules. In the
      last decade, large-scale genomics-based technologies have emerged. Among them,
      the Reverse Vaccinology approach was successfully applied to the development of
      an innovative vaccine against Neisseria meningitidis serogroup B, now available
      on the market with the commercial name BEXSERO(r) (Novartis Vaccines). The
      limiting step of such approaches is the number of antigens to be tested in in
      vivo models. Several laboratories have been trying to refine the original
      approach in order to get to the identification of the relevant antigens straight
      from the genome. Here we report a new bioinformatics tool that moves a first step
      in this direction. The tool has been developed by identifying
      structural/functional features recurring in known bacterial protective antigens,
      the so called "Protectome space," and using such "protective signatures" for
      protective antigen discovery. In particular, we applied this new approach to
      Staphylococcus aureus and Group B Streptococcus and we show that not only already
      known protective antigens were re-discovered, but also two new protective
      antigens were identified. 

PMID- 25368411
TI  - Nic1 inactivation enables stable isotope labeling with 13C615N4-arginine in
      Schizosaccharomyces pombe.
AB  - Stable Isotope Labeling by Amino Acids (SILAC) is a commonly used method in
      quantitative proteomics. Because of compatibility with trypsin digestion,
      arginine and lysine are the most widely used amino acids for SILAC labeling. We
      observed that Schizosaccharomyces pombe (fission yeast) cannot be labeled with a
      specific form of arginine, (13)C(6) (15)N(4)-arginine (Arg-10), which limits the
      exploitation of SILAC technology in this model organism. We hypothesized that in
      the fission yeast the guanidinium group of (13)C(6) (15)N(4)-arginine is
      catabolized by arginase and urease activity to (15)N1-labeled ammonia that is
      used as a precursor for general amino acid biosynthesis. We show that disruption
      of Ni(2+)-dependent urease activity, through deletion of the sole Ni(2+)
      transporter Nic1, blocks this recycling in ammonium-supplemented EMMG medium to
      enable (13)C(6) (15)N(4)-arginine labeling for SILAC strategies in S. pombe.
      Finally, we employed Arg-10 in a triple-SILAC experiment to perform quantitative
      comparison of G1 + S, M, and G2 cell cycle phases in S. pombe.

PMID- 25368412
TI  - Epitope identification from fixed-complexity random-sequence peptide microarrays.
AB  - Antibodies play an important role in modern science and medicine. They are
      essential in many biological assays and have emerged as an important class of
      therapeutics. Unfortunately, current methods for mapping antibody epitopes
      require costly synthesis or enrichment steps, and no low-cost universal platform
      exists. In order to address this, we tested a random-sequence peptide microarray
      consisting of over 330,000 unique peptide sequences sampling 83% of all possible
      tetramers and 27% of pentamers. It is a single, unbiased platform that can be
      used in many different types of tests, it does not rely on informatic selection
      of peptides for a particular proteome, and it does not require iterative rounds
      of selection. In order to optimize the platform, we developed an algorithm that
      considers the significance of k-length peptide subsequences (k-mers) within
      selected peptides that come from the microarray. We tested eight monoclonal
      antibodies and seven infectious disease cohorts. The method correctly identified
      five of the eight monoclonal epitopes and identified both reported and unreported
      epitope candidates in the infectious disease cohorts. This algorithm could
      greatly enhance the utility of random-sequence peptide microarrays by enabling
      rapid epitope mapping and antigen identification. 

PMID- 25368413
TI  - Opting out: confidentiality and availability of an 'alibi' for potential living
      kidney donors in the USA.
AB  - Ethicists and guidelines have suggested that potential living kidney donors who
      withdraw from evaluation be offered an 'alibi.' We sought to determine what
      potential living kidney donors are told about their ability to opt out, alibi
      availability and postwithdrawal confidentiality. We reviewed 148 consent forms
      for living kidney donor evaluation from US transplant centres that performed >5
      living kidney transplants in 2010-2011 (response rate 87%). We found that while
      98% of centres used evaluation consent forms that indicated that the donor could
      withdraw, only 21% of these documents offered an alibi. Another 23% of centres'
      consent forms indicated that the transplant team would be willing to inform the
      intended recipient that an individual was not a potential donor. Relatively few
      consent documents explicitly addressed the confidentiality of the donor's health
      information (31%), candidacy status (18%), decision (24%) or reasons (23%)
      following withdrawal. To preserve potential donors' autonomy and relationships,
      we advocate that all transplant centres offer general alibis in their evaluation
      consent forms. We conclude by offering recommendations for evaluation consent
      discussions of opting out, alibis and postwithdrawal confidentiality. 

PMID- 25368414
TI  - A NusG paralogue from Mycobacterium tuberculosis, Rv0639, has evolved to interact
      with ribosomal protein S10 (Rv0700) but not to function as a transcription
      elongation-termination factor.
AB  - NusG, a well-conserved protein in all the three forms of life, is involved in
      transcription elongation and termination, as well as in the process of
      transcription-translation coupling. The existence of species-specific functional,
      as well as conformational, divergences in NusG makes it an attractive
      transcription factor to study, especially if it originates from a pathogen. Here,
      we report functional and conformational characterizations of the Mycobacterium
      tuberculosis (Mtb) protein Rv0639 that has been annotated as a homologue of
      Escherichia coli NusG. Rv0639 failed to complement the in vivo functions of E.
      coli NusG (Ec NusG) and did not exhibit any signature of a transcription
      elongation-termination factor. However, it retained the ability to bind to its
      cognate ribosomal protein S10 (Rv0700). Compared with Ec NusG, Rv0639 possesses
      unique conformational features characterized by altered secondary structures in
      the C-terminal domain (CTD), an unusually long and disordered linker region
      between the N-terminal domain (NTD) and CTD, and a folding of its NTD over its
      CTD. This unusual folded conformation could have imparted specialized functions
      to this protein, required to adapt the physiology of Mtb. We speculate that in
      the absence of a bona fide RfaH, a NusG paralogue that is involved in
      pathogenicity in E. coli, Rv0639 functions as an RfaH-like factor and is involved
      in pathogenicity using unidentified ops-like sequences in the Mtb genome. And
      hence, we reannotate Rv0639 as a paralogue of NusG, instead of a homologue. 

PMID- 25368415
TI  - Quantitative cell biology: transforming the conceptual, theoretical,
      instrumental, and methodological approaches to cell biology.

PMID- 25368416
TI  - Quantitative cell biology: the essential role of theory.
AB  - Quantitative biology is a hot area, as evidenced by the recent establishment of
      institutes, graduate programs, and conferences with that name. But what is
      quantitative biology? What should it be? And how can it contribute to solving the
      big questions in biology? The past decade has seen very rapid development of
      quantitative experimental techniques, especially at the single-molecule and
      single-cell levels. In this essay, I argue that quantitative biology is much more
      than just the quantitation of these experimental results. Instead, it should be
      the application of the scientific method by which measurement is directed toward
      testing theories. In this view, quantitative biology is the recognition that
      theory and models play critical roles in biology, as they do in physics and
      engineering. By tying together experiment and theory, quantitative biology
      promises a deeper understanding of underlying mechanisms, when the theory works,
      or to new discoveries, when it does not. 

PMID- 25368417
TI  - Beware the tail that wags the dog: informal and formal models in biology.
AB  - Informal models have always been used in biology to guide thinking and devise
      experiments. In recent years, formal mathematical models have also been widely
      introduced. It is sometimes suggested that formal models are inherently superior
      to informal ones and that biology should develop along the lines of physics or
      economics by replacing the latter with the former. Here I suggest to the contrary
      that progress in biology requires a better integration of the formal with the
      informal. 

PMID- 25368418
TI  - Modularity and predictability in cell signaling and decision making.
AB  - Cells make decisions to differentiate, divide, or apoptose based on multiple
      signals of internal and external origin. These decisions are discrete outputs
      from dynamic networks comprised of signaling pathways. Yet the validity of this
      decomposition of regulatory proteins into distinct pathways is unclear because
      many regulatory proteins are pleiotropic and interact through cross-talk with
      components of other pathways. In addition to the deterministic complexity of
      interconnected networks, there is stochastic complexity arising from the
      fluctuations in concentrations of regulatory molecules. Even within a genetically
      identical population of cells grown in the same environment, cell-to-cell
      variations in mRNA and protein concentrations can be as high as 50% in yeast and
      even higher in mammalian cells. Thus, if everything is connected and stochastic,
      what hope could we have for a quantitative understanding of cellular decisions?
      Here we discuss the implications of recent advances in genomics, single-cell, and
      single-cell genomics technology for network modularity and cellular decisions. On
      the basis of these recent advances, we argue that most gene expression
      stochasticity and pathway interconnectivity is nonfunctional and that cellular
      decisions are likely much more predictable than previously expected. 

PMID- 25368419
TI  - Nucleosomes, transcription, and probability.
AB  - Speaking of current measurements on single ion channel molecules, David Colquhoun
      wrote in 2006, "Individual molecules behave randomly, so suddenly we had to learn
      how to deal with stochastic processes." Here I describe theoretical efforts to
      understand recent experimental observations on the chromatin structure of single
      gene molecules, a molecular biologist's path toward probabilistic theories. 

PMID- 25368420
TI  - Multistep phosphorylation systems: tunable components of biological signaling
      circuits.
AB  - Multisite phosphorylation of proteins is a powerful signal processing mechanism
      that plays crucial roles in cell division and differentiation as well as in
      disease. We recently demonstrated a novel phenomenon in cell cycle regulation by
      showing that cyclin-dependent kinase-dependent multisite phosphorylation of a
      crucial substrate is performed sequentially in the N-to-C terminal direction
      along the disordered protein. The process is controlled by key parameters,
      including the distance between phosphorylation sites, the distribution of serines
      and threonines in sites, and the position of docking motifs. According to our
      model, linear patterns of phosphorylation along disordered protein segments
      determine the signal-response function of a multisite phosphorylation switch.
      Here we discuss the general advantages and engineering principles of multisite
      phosphorylation networks as processors of kinase signals. We also address the
      idea of using the mechanistic logic of linear multisite phosphorylation networks
      to design circuits for synthetic biology applications. 

PMID- 25368421
TI  - Emergent mechanics of biological structures.
AB  - Mechanical force organizes life at all scales, from molecules to cells and
      tissues. Although we have made remarkable progress unraveling the mechanics of
      life's individual building blocks, our understanding of how they give rise to the
      mechanics of larger-scale biological structures is still poor. Unlike the
      engineered macroscopic structures that we commonly build, biological structures
      are dynamic and self-organize: they sculpt themselves and change their own
      architecture, and they have structural building blocks that generate force and
      constantly come on and off. A description of such structures defies current
      traditional mechanical frameworks. It requires approaches that account for active
      force-generating parts and for the formation of spatial and temporal patterns
      utilizing a diverse array of building blocks. In this Perspective, we term this
      framework "emergent mechanics." Through examples at molecular, cellular, and
      tissue scales, we highlight challenges and opportunities in quantitatively
      understanding the emergent mechanics of biological structures and the need for
      new conceptual frameworks and experimental tools on the way ahead. 

PMID- 25368422
TI  - Nuclear physics (of the cell, not the atom).
AB  - The nucleus is physically distinct from the cytoplasm in ways that suggest new
      ideas and approaches for interrogating the operation of this organelle. Chemical
      bond formation and breakage underlie the lives of cells, but as this special
      issue of Molecular Biology of the Cell attests, the nonchemical aspects of cell
      nuclei present a new frontier to biologists and biophysicists.

PMID- 25368423
TI  - Extracting meaning from biological imaging data.
AB  - Biological imaging continues to improve, capturing continually longer-term,
      richer, and more complex data, penetrating deeper into live tissue. How do we
      gain insight into the dynamic processes of disease and development from terabytes
      of multidimensional image data? Here I describe a collaborative approach to
      extracting meaning from biological imaging data. The collaboration consists of
      teams of biologists and engineers working together. Custom computational tools
      are built to best exploit application-specific knowledge in order to visualize
      and analyze large and complex data sets. The image data are summarized,
      extracting and modeling the features that capture the objects and relationships
      in the data. The summarization is validated, the results visualized, and errors
      corrected as needed. Finally, the customized analysis and visualization tools
      together with the image data and the summarization results are shared. This
      Perspective provides a brief guide to the mathematical ideas that rigorously
      quantify the notion of extracting meaning from biological image, and to the
      practical approaches that have been used to apply these ideas to a wide range of
      applications in cell and tissue optical imaging. 

PMID- 25368424
TI  - Challenges and dreams: physics of weak interactions essential to life.
AB  - Biological systems display stunning capacities to self-organize. Moreover, their
      subcellular architectures are dynamic and responsive to changing needs and
      conditions. Key to these properties are manifold weak "quinary" interactions that
      have evolved to create specific spatial networks of macromolecules. These
      specific arrangements of molecules enable signals to be propagated over distances
      much greater than molecular dimensions, create phase separations that define
      functional regions in cells, and amplify cellular responses to changes in their
      environments. A major challenge is to develop biochemical tools and physical
      models to describe the panoply of weak interactions operating in cells. We also
      need better approaches to measure the biases in the spatial distributions of
      cellular macromolecules that result from the integrated action of multiple weak
      interactions. Partnerships between cell biologists, biochemists, and physicists
      are required to deploy these methods. Together these approaches will help us
      realize the dream of understanding the biological "glue" that sustains life at a
      molecular and cellular level. 

PMID- 25368425
TI  - Teaching quantitative biology: goals, assessments, and resources.
AB  - More than a decade has passed since the publication of BIO2010, calling for an
      increased emphasis on quantitative skills in the undergraduate biology
      curriculum. In that time, relatively few papers have been published that describe
      educational innovations in quantitative biology or provide evidence of their
      effects on students. Using a "backward design" framework, we lay out quantitative
      skill and attitude goals, assessment strategies, and teaching resources to help
      biologists teach more quantitatively. Collaborations between quantitative
      biologists and education researchers are necessary to develop a broader and more
      appropriate suite of assessment tools, and to provide much-needed evidence on how
      particular teaching strategies affect biology students' quantitative skill
      development and attitudes toward quantitative work. 

PMID- 25368426
TI  - Quantitative biology: where modern biology meets physical sciences.
AB  - Quantitative methods and approaches have been playing an increasingly important
      role in cell biology in recent years. They involve making accurate measurements
      to test a predefined hypothesis in order to compare experimental data with
      predictions generated by theoretical models, an approach that has benefited
      physicists for decades. Building quantitative models in experimental biology not
      only has led to discoveries of counterintuitive phenomena but has also opened up
      novel research directions. To make the biological sciences more quantitative, we
      believe a two-pronged approach needs to be taken. First, graduate training needs
      to be revamped to ensure biology students are adequately trained in physical and
      mathematical sciences and vice versa. Second, students of both the biological and
      the physical sciences need to be provided adequate opportunities for hands-on
      engagement with the methods and approaches necessary to be able to work at the
      intersection of the biological and physical sciences. We present the annual
      Physiology Course organized at the Marine Biological Laboratory (Woods Hole, MA)
      as a case study for a hands-on training program that gives young scientists the
      opportunity not only to acquire the tools of quantitative biology but also to
      develop the necessary thought processes that will enable them to bridge the gap
      between these disciplines. 

PMID- 25368427
TI  - Spatial trigger waves: positive feedback gets you a long way.
AB  - Trigger waves are a recurring biological phenomenon involved in transmitting
      information quickly and reliably over large distances. Well-characterized
      examples include action potentials propagating along the axon of a neuron,
      calcium waves in various tissues, and mitotic waves in Xenopus eggs. Here we use
      the FitzHugh-Nagumo model, a simple model inspired by the action potential that
      is widely used in physics and theoretical biology, to examine different types of
      trigger waves-spatial switches, pulses, and oscillations-and to show how they
      arise.

PMID- 25368428
TI  - Mechanistic modeling confronts the complexity of molecular cell biology.
AB  - Mechanistic modeling has the potential to transform how cell biologists contend
      with the inescapable complexity of modern biology. I am a physiologist-electrical
      engineer-systems biologist who has been working at the level of cell biology for
      the past 24 years. This perspective aims 1) to convey why we build models, 2) to
      enumerate the major approaches to modeling and their philosophical differences,
      3) to address some recurrent concerns raised by experimentalists, and then 4) to
      imagine a future in which teams of experimentalists and modelers build-and
      subject to exhaustive experimental tests-models covering the entire spectrum from
      molecular cell biology to human pathophysiology. There is, in my view, no
      technical obstacle to this future, but it will require some plasticity in the
      biological research mind-set. 

PMID- 25368429
TI  - The quantified cell.
AB  - The microscopic world of a cell can be as alien to our human-centered intuition
      as the confinement of quarks within protons or the event horizon of a black hole.
      We are prone to thinking by analogy-Golgi cisternae stack like pancakes, red
      blood cells look like donuts-but very little in our human experience is truly
      comparable to the immensely crowded, membrane-subdivided interior of a eukaryotic
      cell or the intricately layered structures of a mammalian tissue. So in our daily
      efforts to understand how cells work, we are faced with a challenge: how do we
      develop intuition that works at the microscopic scale? 

PMID- 25368430
TI  - MUC1-C Induces the LIN28B->LET-7->HMGA2 Axis to Regulate Self-Renewal in NSCLC.
AB  - The LIN28B->let-7 pathway contributes to regulation of the epithelial-mesenchymal
      transition (EMT) and stem cell self-renewal. The oncogenic MUC1-C transmembrane
      protein is aberrantly overexpressed in lung and other carcinomas; however, there
      is no known association between MUC1-C and the LIN28B->let-7 pathway. Here in non
      small cell lung cancer (NSCLC), silencing MUC1-C downregulates the RNA-binding
      protein LIN28B and coordinately increases the miRNA let-7. Targeting MUC1-C
      function with a dominant-negative mutant or a peptide inhibitor provided
      confirming evidence that MUC1-C induces LIN28B->let-7 signaling. Mechanistically,
      MUC1-C promotes NF-kappaB p65 chromatin occupancy of the LIN28B first intron and
      activates LIN28B transcription, which is associated with suppression of let-7.
      Consistent with let-7-mediated inhibition of HMGA2 transcripts, targeting of MUC1
      C also decreases HMGA2 expression. HMGA2 has been linked to stemness, and
      functions as a competing endogenous RNA (ceRNA) of let-7-mediated regulation of
      the TGFbeta coreceptor TGFBR3. Accordingly, targeting MUC1-C suppresses HMGA2
      mRNA and protein, which is associated with decreases in TGFBR3, reversal of the
      EMT phenotype, and inhibition of self-renewal capacity. These findings support a
      model in which MUC1-C activates the ?LIN28B->?let-7->?HMGA2 axis in NSCLC and
      thereby promotes EMT traits and stemness. IMPLICATIONS: A novel pathway is
      defined in which MUC1-C drives LIN28B->let-7->HMGA2 signaling, EMT, and self
      renewal in NSCLC.

PMID- 25368431
TI  - The Tyrosine Kinase Adaptor Protein FRS2 Is Oncogenic and Amplified in High-Grade
      Serous Ovarian Cancer.
AB  - High-grade serous ovarian cancers (HGSOC) are characterized by widespread
      recurrent regions of copy-number gain and loss. Here, we interrogated 50 genes
      that are recurrently amplified in HGSOC and essential for cancer proliferation
      and survival in ovarian cancer cell lines. FRS2 is one of the 50 genes located on
      chromosomal region 12q15 that is focally amplified in 12.5% of HGSOC. We found
      that FRS2-amplified cancer cell lines are dependent on FRS2 expression, and that
      FRS2 overexpression in immortalized human cell lines conferred the ability to
      grow in an anchorage-independent manner and as tumors in immunodeficient mice.
      FRS2, an adaptor protein in the FGFR pathway, induces downstream activation of
      the Ras-MAPK pathway. These observations identify FRS2 as an oncogene in a subset
      of HGSOC that harbor FRS2 amplifications. IMPLICATIONS: These studies identify
      FRS2 as an amplified oncogene in a subset of HGSOC. FRS2 expression is essential
      to ovarian cancer cells that harbor 12q15 amplification.

PMID- 25368433
TI  - Authentication of dried distilled grain with solubles (DDGS) by fatty acid and
      volatile profiling.
AB  - Demand for ethanol substituted fuels from the utilisation of cereal based biofuel
      has resulted in an over production of dried distillers grains with solubles
      (DDGS) that are now readily available on the animal feed market. With this rapid
      emerging availability comes potential variability in the nutritional value of
      DDGS and possible risks of feed contaminants. Subsequently, the authentication
      and traceability of alternative animal feed sources is of high priority. In this
      study and as part of the EU research project "Quality and Safety of Feeds and
      Food for Europe (QSAFFE FP7-KBBE-2010-4) an attempt was made to classify the
      geographical origin of cereal grains used in the production of DDGS material.
      DDGS material of wheat and corn origin were obtained from Europe, China, and the
      USA. Fatty acid profiles and volatile fingerprints were assessed by gas
      chromatography flame ionisation (GC-FID) and rapid proton transfer reaction mass
      spectrometry (PTR-MS) respectively. Chemometric analysis of fatty acid profiles
      and volatile fingerprints allowed for promising classifications of cereals used
      in DDGS material by geographical and botanical origin and enabled visual
      representation of the data. This objective analytical approach could be adapted
      for routine verification of cereal grains used in the production of DDGS
      material.

PMID- 25368434
TI  - Rapid synthesis of alkoxyamine hydrochloride derivatives from alkyl bromide and
      N,N'-di-tert-butoxycarbonylhydroxylamine ((Boc)2NOH).
AB  - The conventional route to alkoxyamine hydrochloride derivatives is by reaction of
      alkyl bromides with N-hydroxyphthalimide or N-hydroxysuccinimide followed by
      addition of hydrazine and HCl. Transformation of an alkyl bromide to the
      corresponding alkoxyamine hydrochloride can be accomplished more rapidly in high
      yield and without using hazardous hydrazine by reaction of (Boc)2NOH (N,N'-di
      tert-butoxycarbonylhydroxylamine) and alkyl bromide followed by addition of HCl.
      Alkoxyamine hydrochlorides are powerful reagents in organic synthesis that can be
      used to synthesize alkoxyimino derivatives after condensation with a ketone or
      aldehyde.

PMID- 25368432
TI  - Application of fluorescence resonance energy transfer in protein studies.
AB  - Since the physical process of fluorescence resonance energy transfer (FRET) was
      elucidated more than six decades ago, this peculiar fluorescence phenomenon has
      turned into a powerful tool for biomedical research due to its compatibility in
      scale with biological molecules as well as rapid developments in novel
      fluorophores and optical detection techniques. A wide variety of FRET approaches
      have been devised, each with its own advantages and drawbacks. Especially in the
      last decade or so, we are witnessing a flourish of FRET applications in
      biological investigations, many of which exemplify clever experimental design and
      rigorous analysis. Here we review the current stage of FRET methods development
      with the main focus on its applications in protein studies in biological systems,
      by summarizing the basic components of FRET techniques, most established
      quantification methods, as well as potential pitfalls, illustrated by example
      applications.

PMID- 25368435
TI  - Optimizing Sedative Dose in Preterm Infants Undergoing Treatment for Respiratory
      Distress Syndrome.
AB  - The Intubation-Surfactant-Extubation (INSURE) procedure is used worldwide to
      treat pre-term newborn infants suffering from respiratory distress syndrome,
      which is caused by an insufficient amount of the chemical surfactant in the
      lungs. With INSURE, the infant is intubated, surfactant is administered via the
      tube to the trachea, and at completion the infant is extubated. This improves the
      infant's ability to breathe and thus decreases the risk of long term neurological
      or motor disabilities. To perform the intubation safely, the newborn infant first
      must be sedated. Despite extensive experience with INSURE, there is no consensus
      on what sedative dose is best. This paper describes a Bayesian sequentially
      adaptive design for a multi-institution clinical trial to optimize the sedative
      dose given to pre-term infants undergoing the INSURE procedure. The design is
      based on three clinical outcomes, two efficacy and one adverse, using elicited
      numerical utilities of the eight possible elementary outcomes. A flexible
      Bayesian parametric trivariate dose-outcome model is assumed, with the prior
      derived from elicited mean outcome probabilities. Doses are chosen adaptively for
      successive cohorts of infants using posterior mean utilities, subject to safety
      and efficacy constraints. A computer simulation study of the design is presented.

PMID- 25368436
TI  - Functional Principal Component Analysis of Spatio-Temporal Point Processes with
      Applications in Disease Surveillance.
AB  - In disease surveillance applications, the disease events are modeled by spatio
      temporal point processes. We propose a new class of semiparametric generalized
      linear mixed model for such data, where the event rate is related to some known
      risk factors and some unknown latent random effects. We model the latent spatio
      temporal process as spatially correlated functional data, and propose Poisson
      maximum likelihood and composite likelihood methods based on spline
      approximations to estimate the mean and covariance functions of the latent
      process. By performing functional principal component analysis to the latent
      process, we can better understand the correlation structure in the point process.
      We also propose an empirical Bayes method to predict the latent spatial random
      effects, which can help highlight hot areas with unusually high event rates.
      Under an increasing domain and increasing knots asymptotic framework, we
      establish the asymptotic distribution for the parametric components in the model
      and the asymptotic convergence rates for the functional principal component
      estimators. We illustrate the methodology through a simulation study and an
      application to the Connecticut Tumor Registry data.

PMID- 25368437
TI  - Behavioral Health Competence: An Exploration of Army Reserve Occupational
      Therapists.
AB  - The behavioral health competence of Army Reserve Occupational Therapists (OT) was
      examined by electronic survey to determine current levels of competence and
      highlight pre-deployment training needs. Results indicated that while Army
      Reserve OTs report high levels of behavioral health competence, many questions
      regarding diagnosis, assessment, evaluation, treatment planning, intervention,
      and progress arose throughout deployment. OT's often relied on skills from Level
      II fieldwork education and entry-level didactic education for competency.
      Perceived competencies may be compromised by curriculum changes in entry-level
      education, available fieldwork settings, and a lack of adequate training
      currently available prior to deployment.

PMID- 25368438
TI  - A Double-Edged Sword: Race, Daily Family Support Exchanges, and Daily Well-Being.
AB  - This study contributes to research on race and family ties by exploring racial
      differences in the direct effects of family support exchanges on daily well-being
      and the extent to which family support buffers/exacerbates stressor reactivity.
      African Americans and European Americans aged 34 to 84 (N = 1,931) from the
      National Study of Daily Experiences (NSDE) reported on family support exchanges
      (i.e., support received/support provided), daily stressors, and negative affect
      during 8 days of telephone interviews. On a daily basis, receiving family support
      was not associated with well-being, whereas providing family support was
      associated with compromised well-being among African Americans. As expected,
      receiving family support buffered reactivity to daily tensions for both races,
      whereas providing emotional support to family exacerbated African Americans'
      reactivity to daily tensions. Together, our findings suggest that even after
      considering the benefits of receiving family support, providing family support
      takes an emotional toll on African Americans.

PMID- 25368440
TI  - The enzymatic reaction catalyzed by lactate dehydrogenase exhibits one dominant
      reaction path.
AB  - Enzymes are the most efficient chemical catalysts known, but the exact nature of
      chemical barrier crossing in enzymes is not fully understood. Application of
      transition state theory to enzymatic reactions indicates that the rates of all
      possible reaction paths, weighted by their relative probabilities, must be
      considered in order to achieve an accurate calculation of the overall rate.
      Previous studies in our group have shown a single mechanism for enzymatic barrier
      passage in human heart lactate dehydrogenase (LDH). To ensure that this result
      was not due to our methodology insufficiently sampling reactive phase space, we
      implement high-perturbation transition path sampling in both microcanonical and
      canonical regimes for the reaction catalyzed by human heart LDH. We find that,
      although multiple, distinct paths through reactive phase space are possible for
      this enzymatic reaction, one specific reaction path is dominant. Since the
      frequency of these paths in a canonical ensemble is inversely proportional to the
      free energy barriers separating them from other regions of phase space, we
      conclude that the rarer reaction paths are likely to have a negligible
      contribution. Furthermore, the non-dominate reaction paths correspond to altered
      reactive conformations and only occur after multiple steps of high perturbation,
      suggesting that these paths may be the result of non-biologically significant
      changes to the structure of the enzymatic active site.

PMID- 25368439
TI  - Physella acuta: atypical mitochondrial gene order among panpulmonates
      (Gastropoda).
AB  - Mitochondrial (mt) sequences are frequently used for phylogenetic reconstruction
      and for identification of species of molluscs. This study expands the
      phylogenetic range of Hygrophila (Panpulmonata) for which such sequence data are
      available by characterizing the full mt genome of the invasive freshwater snail
      Physella acuta (Physidae). The mt genome sequences of two P. acuta isolates from
      Stubblefield Lake, New Mexico, USA, differed in length (14,490 vs 14,314 bp) and
      showed 11.49% sequence divergence, whereas ITS1 and ITS2 sequences from the
      nuclear genome differed by 1.75%. The mt gene order of P. acuta (cox1, P, nad6,
      nad5, nad1, D, F, cox2, Y, W, nad4L, C, Q, atp6, R, E, rrnS, M, T, cox3, I, nad2,
      K, V, rrnL, L1, A, cytb, G, H, L2, atp8, N, nad2, S1, S2, nad4) differs
      considerably from the relatively conserved gene order within Panpulmonata.
      Phylogenetic trees show that the 13 protein-encoding mt gene sequences
      (equivalent codons) of P. acuta group according to gastropod phylogeny, yet
      branch lengths and dN/dS ratios for P. acuta indicate elevated amino acid
      substitutions relative to other gastropods. This study indicates that mt
      sequences of P. acuta are phylogenetically informative despite a considerable
      intraspecific divergence and the atypical gene order in its mt genome.

PMID- 25368441
TI  - Laser therapy two decades on: the phoenix flourishes.

PMID- 25368442
TI  - Ex vivo efficacy evaluation of laser vaporization for treatment of benign
      prostatic hyperplasia using a 300-W high-power laser diode with a wavelength of
      980 nm.
AB  - BACKGROUND AND OBJECTIVE: Laser vaporization of the prostate is considered to be
      a promising treatment for benign prostatic hyperplasia (BPH), and efficiency of
      vaporization and hemostasis are both important parameters for such treatment. In
      this study, we used a high-power laser diode with a wavelength of 980 nm to
      obtain high vaporization efficiency with good hemostasis. The objective of this
      study is to evaluate the efficacy of laser vaporization for treatment of BPH in
      ex vivo experiments using a 300-W high-power laser diode with a wavelength of 980
      nm quantitatively. MATERIALS AND METHODS: An ex vivo experimental setup
      simulating clinical treatment situation was constructed. Bovine prostate tissue
      was used as a sample. The power setting was 100, 150, 200, 250, or 300 W, and the
      irradiation time was 0.5, 1, or 2 s. After laser irradiation, vaporized and
      coagulated depths were measured. RESULTS: The vaporized depth increased with the
      laser power and irradiation time, and the results confirmed that the high-power
      laser diode could efficiently vaporize the prostate tissue. Coagulated depth
      increased as the laser power became higher. CONCLUSIONS: Laser vaporization of
      prostate tissue using a high-power laser diode with a wavelength of 980 nm
      represents a promising treatment for BPH; this method exhibits high vaporization
      efficiency and good hemostasis. However, operators must be aware of the risk of
      postoperative perforation of the prostatic capsule caused by coagulation of deep
      regions that cannot be visualized by endoscopic observation.

PMID- 25368443
TI  - The use of sub-ablative Er:YAG laser irradiation in prevention of dental caries
      during orthodontic treatment.
AB  - PURPOSE: This " in-vitro " study had two specific aims: the first, to test using
      a universal testing machine whether sub-ablative Er:YAG laser irradiation prior
      to acid etching is effective in orthodontic bracket bonding and secondly using
      micro-hardness measurements and Scanning Electron Microscopy (SEM) observations
      to investigate the effectiveness of de-mineralization reduction in enamel treated
      with sub-ablative Er:YAG laser irradiation followed by fluoride varnish
      application. MATERIALS AND METHODS: One hundred and eighty bovine permanent
      maxillary incisors were selected for shear bond strength testing and
      microhardness measurements. Sub-ablative Er:YAG laser irradiation was set at a
      power density of 2.5 J/cm(2), a frequency of 7 Hz and air/water spray. Brackets
      were bonded with an auto-curing resin paste. The shear bond strength was measured
      comparing laser irradiated and non-irradiated enamel surface, followed by SEM
      observation of the bracket-resin-enamel interface. Microhardness measurements
      were made on enamel samples before treatment, after samples preparation, and
      after demineralization. RESULTS: While the adhesion of orthodontic brackets to
      bovine enamel after sub-ablative Er:YAG laser irradiation and acid etching is
      comparable to that obtained after conventional acid etching, the effect of laser
      irradiation associated with topical application of fluoride varnish increases the
      microhardness of enamel. CONCLUSION: Sub-ablative Er:YAG laser irradiation before
      the acid etching doesn't reduce the shear bond whereas when associated with
      fluoride application it may play a role in caries prevention. Further studies
      will be necessary to establish the mechanism by which the protective laser
      activated fluoride effect is achieved.

PMID- 25368444
TI  - A new standard of Efficacy for Low Level Laser Therapy (LLLT) in Pain Attenuation
      in Japan (a secondary publication).
AB  - The assessment of the efficacy of low level laser therapy (LLLT) for pain
      attenuation varies among institutions, all having their own method of assessment
      with no common standards. At the author's institution in the beginning, the
      patients were asked how they assessed their pain relief immediately after the
      treatment. They were to choose from excellent, good, fair, no change and poor.
      The overall efficacy rate was calculated by the numbers of patients scoring
      excellent and good, expressed as a percentage of the total number of patients.
      However, a large number of institutions have utilized the Visual Analogue Scale
      (VAS) or the Pain Relief Score (PRS) for the assessment of treatment; but even
      then, the evaluation could not be considered uniform. Therefore, the
      standardization of the efficacy rate was continuously discussed among the
      practitioners of LLLT, dating back to the 9(th) annual meeting of the Japan Laser
      Therapy Association (JaLTA) in 1997. It took four years (including the 1997
      meeting) until finally an agreement was reached and a new standard of efficacy
      was presented at the 12(th) JaLTA meeting in 2000, based on the PRS. The new
      standard defined excellent as pain reduction in any treatment session from 10 to
      0 or 1, good as reduction from 10 to 2~5, fair as reduction from 10 to 6~8, no
      change as a reduction from 10 to 9~10 and poor was defined as exacerbation of
      pain from 10 to 11 or greater. Efficacy rate was calculated by the number of
      patients scoring excellent and good expressed as a percentage of the total number
      of patients. For the purpose of reference, the VAS was to be used for patients
      receiving the treatment for the first time. 

PMID- 25368445
TI  - Anti-inflammatory activities of light emitting diode irradiation on collagen
      induced arthritis in mice (a secondary publication).
AB  - BACKGROUND AND AIMS: Rheumatoid arthritis (RA) is an auto-immune disease
      afflicting multiple joints of the body, where as a result of the increase in
      inflammatory cytokines and tissue destructive factors such as matrix
      metalloproteinase (MMP)-3, deterioration of the bones and cartilages of the
      joints occurs. The present investigation was carried out to study the anti
      inflammatory activities of light emitting diode (LED) irradiation on hind paw
      inflammation in collagen-induced arthritis (CIA) mice models. MATERIALS AND
      METHOD: RA in the CIA mouse model was induced by immunization of DBA/1J mice with
      intradermal injections of an emulsion of bovine type II collagen and complete
      Freund's adjuvant. A total of 20 CIA mice were subdivided into the following
      groups: control group, CIA group and 2 groups of LED irradiated CIA mice (LED
      groups) (n=5 per group). The mouse knee joint area in the LED groups (the 570 nm
      and 940 nm groups) was irradiated with LED energy, three times a week for 500 s
      per session over 8 weeks at a dose of 5 J/cm(2). The hind paw swelling was
      assessed by the increase in hind paw thickness. The serum levels of the
      inflammatory cytokines and arthritic factor MMP-3 were determined with an enzyme
      linked immunosorbent assay (ELISA). RESULTS: In the LED-570 and LED-940 groups at
      4 weeks after arthritis induction, the swelling inhibition index was 18.1+/-4.9
      and 29.3+/-4.0 respectively. Interleukin (IL)-1beta, IL-6 and MMP-3 serum levels
      were significantly lower in the LED-940 group. CONCLUSIONS: LED irradiation,
      particularly in the near-infrared was effective for inhibition of the
      inflammatory reactions caused by RA.

PMID- 25368446
TI  - Usefulness of Photodynamic Diagnosis and Therapy using Talaporfin Sodium for an
      Advanced-aged Patient with Inoperable Gastric Cancer (a secondary publication).
AB  - BACKGROUND AND AIMS: In Japan the rise in the average life expectancy has caused
      an increase in the proportion of the population who are classed as geriatric.
      Accordingly, the number of elderly people being treated for cancer is increasing
      concomitantly. However, with the increase in age, the numbers of prior
      complications also increase. This is especially so in the advanced-aged patients,
      defined in Japan as those over the age of 85. Such complications may be too high
      risk for radical surgery and a less invasive treatment is warranted. Photodynamic
      therapy (PDT) is a noninvasive treatment approved by the Japanese National Health
      Insurance for the treatment of early stage superficial type esophageal and
      gastric cancers, early stage uterine cervical cancers and dysplasia, and early
      and advanced lung cancer. We report herein on the efficacy of palliative PDT
      using talaporfin sodium (Laserphyrin((r))) for a case of inoperable gastric
      cancer. MATERIAL AND METHODS: The patient was an 87-year-old-man, a diabetic with
      histories of diabetic nephropathy, cerebral infarction and myocardial infarction.
      This patient was first diagnosed as having gastric cancer in 2007 but surgery and
      chemotherapy were contraindicated due to his poor physical status and poor renal
      function, respectively, owing to the anticipated side effects. The patient was
      referred to our institution after hearing of PDT in 2009. He was treated with 1
      course of porfimer sodium PDT and 3 courses of talaporfin sodium PDT with
      photodynamic diagnosis (PDD) during the period from September, 2009 to June,
      2011. RESULTS: The massive gastric cancer located in the cardia was successfully
      treated with 4 PDT sessions without any serious complications; therefore the
      patient was able to orally ingest food until his death due to natural causes
      other than the cancer, in October, 2011. CONCLUSION: Talaporfin sodium PDT is
      safe and effective treatment for advanced-aged patients suffering from inoperable
      gastric cancer.

PMID- 25368447
TI  - Treatment of lichen pilaris with a Q-switched Nd:YAG laser in quasi long-pulsed
      mode: A case report (a secondary publication).
AB  - BACKGROUND AND AIMS: Lichen pilaris is a very common disease typically seen among
      young adults on their upper arms as a manifestation of hyperkeratotic lesions
      occurring in the pores. Only a few treatments have been reported as significantly
      effective, so often natural resolution over time is the only option. The present
      study examined the use of a 1064 nm Q-switched Nd:YAG laser (QSNY) in quasi long
      pulsed mode, in an attempt to treat a case of lichen pilaris. SUBJECT AND
      METHODS: A 33-year-old male presented with light-brown aggregated papules
      observed on both sides of the upper arms. The affected areas were treated every
      other week (QSNY, pulse width 300 us, pulse energy 3.0 J/cm(2), spot size 6 mm
      and repetition rate 10 Hz). Clinical photography was taken of the lesions at
      baseline and three months after the final treatment in addition to
      macrophotography and 3-D photography, biopsies being taken at both time points
      for histological comparison. RESULTS: The clinical photography and objective
      image evaluation demonstrated shrinkage of pores and improvement of the
      unevenness of the skin. Histological examination suggested that the effect of the
      micropulsed QSNY on the horny layer, epidermal keratinocytes and dermal collagen
      resulted in a peeling effect and increased dermal collagen density, which
      eventually led to the shrinkage of the pores and improvement of the skin
      condition. CONCLUSIONS: The results of this single patient case report suggest
      that the micropulsed QSNY could be an effective treatment option for lichen
      pilaris, improvement of which is often difficult. Further studies with an
      appropriately-sized population are merited to confirm these preliminary results.

PMID- 25368448
TI  - Trapping and release of cargo molecules from a micro-stamped mesoporous thin film
      controlled by Poly(NIPAAm-co-AAm).
AB  - Materials that utilize the micropatterned structure of a mesoporous silica film
      to successfully load and release cargo using a thermal sensitive polymer are
      presented in this paper. Films with pore sizes of ~2 nm and ~5 nm aligned in the
      pulling direction were synthesized using evaporation induced self-assembly
      techniques. The pores are exposed using a new method of stamping micropatterns
      without the use hydrofluoric acid. A well studied temperature dependent polymer
      (poly(N-isopropylacrylamide-co-Acrylamide)) was grafted onto the surface of these
      films to act as a temperature activated gatekeeper. Below the lower critical
      solution temperature (LCST) the polymer is erect and can block the pore openings,
      trapping cargo inside the pores. When the temperature is above the LCST the
      polymer collapses and unblocks the pores, allowing cargo to escape. The loading
      capacities as well as the reusability of these films were studied.

PMID- 25368449
TI  - Perception of HIV risk and the quantity and quality of children: The case of
      rural Malawi.
AB  - The empirical literature on the impact of HIV on the quality (Q) and quantity (N)
      of children provides limited and somewhat mixed evidence. This study introduces
      individual HIV risk perceptions, as a predictor of mortality, into a Q-N
      investment model. In this model, higher maternal mortality predicts lower N while
      higher child mortality predicts lower Q. Thus the two effects together make
      likely negative associations between HIV and both Q and N. Based on longitudinal
      micro data on mothers and their children in rural Malawi, our results suggest
      that higher mothers' reported HIV risk reduces both child quality, as reflected
      in children's schooling and health, and child quantity, when the perceived risk
      is already moderate or high. The effects are sizable, and, in the case of Q
      (schooling and health) are found for children and teenagers, both boys and girls,
      while in the case of N they are found for young and mature women.

PMID- 25368450
TI  - An Examination of the First Oxford House in the UK: A Preliminary Investigation.
AB  - An exploratory investigation was conducted to examine the implementation of the
      first self-run, communal-living setting based on the Oxford House model, in the
      United Kingdom (UK). A cross-sectional, mixed methods design was used to examine
      the Oxford House model's total abstinence approach to recovery from substance use
      disorders among residents (n = 7) living in the first Oxford House established in
      the UK. Several measures commonly used in addiction research and personal
      narratives were used to assess residents' response to Oxford House living.
      Findings suggest that the Oxford House model is a post-treatment intervention
      that meets the needs of individuals seeking an abstinence-based recovery from
      alcohol and/or drug dependence in the UK.

PMID- 25368451
TI  - Should We be More "Open" About Publishing Research?

PMID- 25368452
TI  - The role of ultrasound in the assessment of uterine cervical cancer.
AB  - Uterine cervical cancer is the second most frequent gynecological malignancy
      worldwide. The assessment of the extent of disease is essential for planning
      optimal treatment. Imaging techniques are increasingly used in the pre-treatment
      work-up of cervical cancer. Currently, MRI for local extent of disease evaluation
      and PET-scan for distant disease assessment are considered as first-line
      techniques. Notwithstanding, in the last few years, ultrasound has gained
      attention as an imaging technique for evaluating women with cervical cancer. In
      this paper, current knowledge about the use of ultrasound for assessing uterine
      cervical cancer will be reviewed and discussed. 

PMID- 25368453
TI  - HPV Vaccine: How Far have We Achieved?
AB  - Globally, cervical cancer is the second most common cancer, and in India, it is
      the most common cancer in women. Human Papilloma virus (HPV) is the main cause of
      it. Although there are several methods for preventing cervical cancer, primary
      prevention by vaccination is the most effective option. HPV vaccine is safe and
      effective. It is expensive and is not a replacement for periodic cervical
      screening procedures. In developing countries, the cost effectiveness of vaccine
      and that of effective screening program with broader coverage is questionable.
      Today, HPV vaccine with regular cervical cancer screening program is the best
      possible tool to prevent cervical cancer. 

PMID- 25368454
TI  - Emergency peripartum hysterectomy in a tertiary care hospital in saudi arabia.
AB  - PURPOSE: Post-partum hemorrhage remains an important cause of significant
      maternal morbidity and mortality throughout the world. The objective of this
      study was to review the incidence, indications, predisposing factors, and
      associated complications of emergency peripartum hysterectomy. METHODS: This is a
      retrospective observational study done in a Tertiary Care Center, Riyadh, Saudi
      Arabia, between 1983 and 2006. Women who underwent emergency peripartum
      hysterectomy after cesarean delivery or following vaginal birth due to severe
      post-partum hemorrhage who did not respond to conservative treatment were
      included in the study. Data were abstracted from chart reviews. Descriptive
      analysis was carried out to summarize relevant variables. Primary outcomes
      included indications, risk factors, maternal morbidity, and mortality. RESULTS:
      There were 66 emergency peripartum hysterectomies among 155,857 deliveries, which
      yielded an incidence of 0.04 %. Prior cesarean delivery was present in 88 % of
      the patients; a majority of the patients were grandmultiparous, Para > 6 (65 %).
      The incidence of hysterectomy after cesarean delivery was much higher than after
      vaginal delivery (0.3 vs. 0.01 %). Common indications included placenta accreta
      (65 %), uterine atony (27 %), and uterine rupture (8 %). The majority of the
      study cohort (64 %) had undergone total hysterectomy. Post-operatively, 25
      patients (38 %) developed DIC, 32 (48.5 %) had febrile illnesses, and 22 (33 %)
      experienced injury to the urinary tract. The maternal mortality in this study was
      4.5 %. CONCLUSIONS: Hysterectomy for the control of obstetric hemorrhage is
      usually associated with significant mortality and morbidity. Prompt intervention
      to include peripartum hysterectomy may likely decrease the rate of maternal
      deaths and significant maternal morbidity.

PMID- 25368455
TI  - Indian perspective on clinical aspects, usage, and guidelines of folic Acid.
AB  - Folic acid (pteroylmonoglutamic acid) is the stable, fully oxidized form of
      folate which is used in food fortification and supplements. Keen interest has
      been generated in folic acid due to its suggested role in prevention of various
      disorders. Strong evidence from clinical trials indicates preventive effect of
      folic acid on both occurrence and recurrence of neural tube defects. It also
      plays a significant role in mitigating the risk of cardiovascular disorders
      through homocysteine regulation. In addition, the beneficial effect of folic acid
      in various types of cancers, neurological disorders, conditions affecting
      pregnancy, and other clinical conditions has been reported in literature. Various
      guidelines reinforce the need for women to obtain adequate amount of folic acid
      either through food fortification or supplements. In India, national guidelines
      on the proper dose of folic acid to pregnant women are not available. Given its
      significant beneficial effects on health, awareness should be spread among
      communities on the usage and benefits of folic acid. 

PMID- 25368456
TI  - HCV and pregnancy: prevalence, risk factors, and pregnancy outcome in north
      Indian population: a case-control study.
AB  - OBJECTIVES: The study was carried out to investigate the prevalence, risk
      factors, and Pregnancy outcome in anti-HCV-positives pregnant women admitted for
      delivery in the Department of Obstetrics & Gynecology of Guru Gobind Singh
      Medical College and Hospital, Faridkot between January 2010 and January 2013.
      SETTING: Department of obstetrics and Gynaecology of GGS Medical College and
      Hospital, Faridkot. MATERIAL AND METHODS: A case-control study design was
      selected for the study. A total of 1412 pregnant women presenting in the labor
      room of our hospital between January 2010 and January 2013 were subjected to anti
      HCV testing by third generation ELISA. Age, parity, and gestational age-matched
      controls were taken from the women delivering during the same time frame who
      tested negative for hepatitis C. All the subjects and controls were non-reactive
      for HIV and HBsAg as well. Risk factors and pregnancy outcome were compared with
      the control group. Approval was taken from ethic committee of the institute. The
      women who consented to participate in the study were evaluated on the basis of a
      questionnaire for the presence of risk factors of hepatitis C and pregnancy
      outcome. Women with the known previous liver disease were excluded from the
      study. Data were analyzed using SPSS for Windows version 16.0. p < 0.05 was
      considered significant. RESULTS: Forty patients tested positive for anti-HCV
      antibodies among 1,412 patients subjected to anti-HCV testing during study
      period. 40 patients were taken as controls, who were negative for anti-HCV
      antibodies. Prevalence of HCV during pregnancy was 2.8 % in our study. Among the
      risk factors studied, previous surgery and blood transfusion were the
      statistically significant risk factors. There was history of previous major
      surgery in 16 cases versus 4 controls and was statistically significant (p value
      0.002) at p < 0.05. History of blood transfusion was present in 4 versus 2 among
      cases and controls, respectively, and statistically significant (p value 0.004)
      at p < 0.05. Sexual transmission was not the risk factor as none of the spouse of
      the pregnant women was positive for HCV antibodies. Neonatal outcome was similar
      in both groups. Pregnancy complications i.e., Pregnancy-induced hypertension and
      antepartum hemorrhage were significantly higher in study group compared to
      control group. CONCLUSION: Incidence of hepatitis C virus infection in pregnancy
      is 2.8 %. Surgical procedures, blood transfusion, are the major risk factors for
      transmission. There are no identifiable risk factors in 35 % of cases. Pregnancy
      complications like Pregnancy-induced hypertension and antepartum hemorrhage are
      more common in HCV-positive mothers. Neonatal outcome is not affected. Universal
      screening of all pregnant women should be done for HCV as many patients may not
      have any risk factor.

PMID- 25368457
TI  - Evaluation of Safety, Efficacy, and Expulsion of Post-Placental and Intra
      Cesarean Insertion of Intrauterine Contraceptive Devices (PPIUCD).
AB  - BACKGROUND: This study examines to describe the factors associated with
      acceptability of immediate PPIUCD insertion in women according to their socio
      demographic and obstetrics characteristics, and future pregnancy desires and to
      determine the rates of uterine perforation, expulsion, pelvic infection, lost
      strings and displacement following PPIUCD insertion among the acceptors by 6 to
      18 months. AIM: An intrauterine device (IUD) is an effective form of Long Acting
      Reversible Contraception. Present study is aimed at determining the safety,
      efficacy, and expulsion of Post-placental and intra-cesarean insertion of
      Intrauterine contraceptive device (PPIUCD). MATERIALS & METHODS: The study was
      conducted at District Head Quarters Hospital, Bolangir, Odisha, India. From 1st.
      January 2012 to 31st. December 2012. Women admitted and delivered at D.H.H.
      Bolangir, were counseled. CuT 380A was inserted within 10 minutes of delivery of
      placenta in accepters who fulfilled the Medical Eligibility Criteria and had no
      contraindications for PPIUCD. They were followed up till 30th June 2013. RESULTS:
      Total women counseled 3209, Accepted 564, Declined 2645, lost to follow up 130,
      Followed up 434, COMPLICATIONS: 190 (Expulsion 39, Bleeding 102, String problem
      49), Removal 43, Continuation 352. CONCLUSIONS: The PPIUCD (Inserting CuT 380 A
      by 10 minutes after placental delivery) was demonstrably safe, effective, has
      high retention rate. The expulsion rate was not very high and it can be reduced
      with practice. With the high level of acceptance despite low levels of awareness,
      the government needs to develop strategies to increase public awareness of the
      PPIUCD through different media sources. It is also important to arrange training
      on PPIUCD in order to increase knowledge and skills among healthcare providers.
      This will also further promote PPIUCD use and aid in reduction of the expulsion
      rates. Cash incentives to the accepter, motivator and of course provider would
      bring about a substantial progress in the PPIUCD use in developing countries like
      India.

PMID- 25368458
TI  - Delayed interval delivery of the second twin: obstetric management, neonatal
      outcomes, and 2-year follow-up.
AB  - OBJECTIVES: To evaluate the obstetric management and neonatal outcomes in twin
      pregnancies with delayed delivery of the second twin, including follow-up.
      METHODS: This study is a review of four cases of delayed delivery of the second
      twin in our hospital from 2009 to 2012. The obstetric management of the cases
      from the expulsion of the first twin to the delivery of the second twin is
      analyzed. The neonatal outcomes including follow-up for 2 years were reviewed.
      RESULTS: The first twins were delivered between 15 and 25 weeks (average 21
      weeks) and the second twins were delivered between 25 and 31 weeks (average 27
      weeks). One first twin (25 %) survived, while three (75 %) second twins survived.
      Two out of the three second twins delivered after 28 weeks were in satisfactory
      condition. CONCLUSIONS: The delayed delivery of the second twins which occurred
      in the third trimester is associated with favorable outcome, however, the risks
      should not be ignored.

PMID- 25368459
TI  - Association of the Position of the Copper T 380A as Determined by the
      Ultrasonography Following its Insertion in the Immediate Postpartum Period with
      the Subsequent Complications: An Observational Study.
AB  - PURPOSE: Incorrectly placed copper T 380A leads to increased contraception
      failure. This study aimed to find an association between the ultrasonographic
      position of the copper T 380A in the immediate postpartum period and the adverse
      effects observed during the period of 6 months after its insertion. METHODS: This
      descriptive study was carried out in the Department of Obstetrics & Gynaecology
      of a tertiary-care-center of India from September 2011 to February 2013. The
      women eligible for immediate postpartum copper T 380A insertion with previous
      regular menstrual cycles for at least 6 months before the current pregnancy, and
      those who were willing for follow-up visits and had easy accessibility to the
      hospital, were recruited. A clinical evaluation and ultrasonographic assessment
      of Intra-Uterine-Contraceptive-Device (IUCD) after insertion was carried out
      after enrolment. The complications (expulsions, vaginal discharge, menstrual
      irregularity, and lower abdominal pain) were subsequently assessed during a 6
      month follow-up period. The primary objective was the ultrasonographic assessment
      of the placement of IUCD immediately after insertion. The incidence of
      complications and their association with the presence of malposition was also
      studied. RESULTS: Hundred patients were evaluated during the study period. Forty
      four (44 %) women were found to have malpositioned IUCDs on ultrasonographic
      evaluation done following insertion. The complications among the IUCD users
      included menstrual irregularity (27.17 %), pain in lower abdomen (20.65 %),
      vaginal discharge (7.6 %), and expulsions (9.7 %). The IUCD expulsions, menstrual
      irregularities, and pain were significantly more in patients with malpositions (p
      < 0.05). CONCLUSIONS: Malpositioning of IUCD is common immediately following
      insertion and is significantly associated with more complications during the
      follow-up.

PMID- 25368460
TI  - Role of ultrasonography in diagnosis of ectopic pregnancy with clinical analysis
      and management in tertiary care hospital.
AB  - PURPOSE OF THE STUDY: This study is undertaken to emphasize the role of
      ultrasonography in the diagnosis of ectopic pregnancy and clinical analysis of
      the same in a tertiary care referral hospital. METHODOLOGY: One hundred patients
      with provisional diagnosis of ectopic pregnancy were studied. Physical
      examination, urine pregnancy test, transabdominal scan using 5 MHz transducer or
      transvaginal ultrasonography of 7 MHz was done. The diagnosis of ectopic
      pregnancy was confirmed by direct observation by laparotomy or laparoscopy (which
      was taken as gold standard). RESULTS: The study showed ectopic pregnancy was most
      common in gravida 2 and in age group 26-30 years with most of them having married
      life <10 years. One or more risk factors were found in 66 % of cases. 54 % of
      cases presented with acute symptoms, 14 % of cases in shock. Among clinical
      presentation pain abdomen, history of amenorrhea, bleeding per vaginum, abdominal
      tenderness, and cervical motion tenderness was most common. In ultrasonography,
      complex mass in adnexa was present in 60 % of cases and hemoperitoneum in 50 %.
      96 % of cases were tubal pregnancy with most of them tubal rupture. In 98 % of
      cases, radical surgery was done. Salpingectomy was the most common surgery done
      (90 %). There was no negative laparotomy in this study. There was no maternal
      mortality in this series. CONCLUSIONS: In all the 100 cases of ectopic pregnancy
      studied, the ultrasonography provided definitive diagnosis resulting in 100 %
      sensitivity and 100 % specificity, predictive value of positive test being 100 %.
      Ultrasonography done in earlier weeks of gestation had sensitivity of 96 % and
      false negative 4 %.

PMID- 25368461
TI  - Intraoperative autologous blood transfusion of peritoneal blood during laparotomy
      for ectopic pregnancy: prospective study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of
      intraoperative autologous blood transfusion during laparotomy for hemoperitoneum
      in ectopic pregnancy and also safety of homologous blood transfusion along with
      autologous blood transfusion. METHOD: Fresh blood, from peritoneal cavity, was
      collected for autotransfusion in sterile dish, filtered through eight layers of
      sterile gauze pieces, and collected in a sterile bowl. The collected blood was
      transferred into blood infusion bag containing citrate phosphate dextrose adenine
      solution in the proportion of five parts of blood to one part of citrate
      solution. RESULTS: Mean volume of autologous blood transfused in patients without
      homologous transfusion was 573 +/- 328. Mean preoperative hemoglobin was 4.95 +/-
      1.5, and postoperative hemoglobin was 6.85 +/- 1.3. Hence, rise in hemoglobin was
      1.9 g%. Autologous blood volume transfused in 29 patients (who required
      homologous blood transfusion) was 488 +/- 216. Preoperative hemoglobin was 4.35
      +/- 1.94. The result was compared with other studies. CONCLUSION: Intraoperative
      autologous blood transfusion enabled the performance of laparotomy in
      hemodynamically unstable ectopic pregnancy patients without availability of
      homologous blood transfusion. Homologous blood transfusion is compatible with
      autologous blood transfusion.

PMID- 25368462
TI  - Post B-lynch uterine rupture: case report and review of literature.

PMID- 25368463
TI  - A Rare Case of Non-puerperal Acute Uterine Inversion.

PMID- 25368464
TI  - Krukenberg tumor secondary to an incidentally discovered gall bladder carcinoma:
      a rare occurrence.

PMID- 25368465
TI  - Ovarian fibromatosis.

PMID- 25368466
TI  - Laparoscopic specimen retrieval bags.
AB  - Specimen retrieval bags have long been used in laparoscopic gynecologic surgery
      for contained removal of adnexal cysts and masses. More recently, the concerns
      regarding spread of malignant cells during mechanical morcellation of myoma have
      led to an additional use of specimen retrieval bags for contained "in-bag"
      morcellation. This review will discuss the indications for use retrieval bags in
      gynecologic endoscopy, and describe the different specimen bags available to
      date. 

PMID- 25368467
TI  - Comment on case report entitled: adenomyosis of uterus with adenomyoma of
      fallopian tube.

PMID- 25368468
TI  - Dermato-trichologist and Acquired Immuno-deficiency Syndrome.

PMID- 25368469
TI  - From science to spirituality.

PMID- 25368470
TI  - Dermoscopic findings of alopecia areata in dark skinned individuals: an analysis
      of 116 cases.
AB  - BACKGROUND: Several dermoscopic findings in alopecia areata (AA) are
      characteristic and aid in the diagnosis of this disease. Studies evaluating the
      clinical significance of these findings in AA in dark-skinned individuals are
      sparse. There is no literature of correlation of dermoscopic findings to severity
      of disease. AIMS: The aim was to determine the dermoscopic findings of AA in dark
      skinned individuals and to assess whether certain dermoscopic findings correlate
      with disease activity and severity. MATERIALS AND METHODS: Totally 116 patients
      with AA were included in the study. After a thorough clinical history and
      examination to note type, severity and activity of the disease, dermoscopy was
      performed using a Heine Delta 20 dermoscope (Heine optotechnik,Herrsching,
      Germany) and the results were noted in a proforma. Statistical analysis was
      performed using SPSS13 software using appropriate statistical tools. RESULTS:
      Dermoscopic findings were nearly similar to that described in western literature.
      Yellow dots (YDs) were found to be highly sensitive for diagnosis, increased
      frequency being seen in Indian prepubertal patients when compared with western
      literature. YDs/field of vision (FOV) were found more frequently in severe types
      of AA. There was no correlation of dermoscopic findings to severity of disease.
      CONCLUSION: Dermoscopic features are similar to that described in the literature.
      However, YDs are seen in higher frequency. YDs/FOV could serve as dermoscopic
      criteria to grade severity of AA.

PMID- 25368471
TI  - Trichoscopy in trichotillomania: a useful diagnostic tool.
AB  - INTRODUCTION: Trichotillomania (TTM) is characterized by patchy alopecia of hair
      bearing areas. This is because of compulsive urge to pull the hair. Scalp is the
      most common site for pulling hair. Usually, patients may have only small areas of
      baldness, in severe forms, tonsure pattern of baldness is observed. Diagnosis is
      by history and clinical examination. However, it is difficult to differentiate
      from other causes of noncicatricial alopecia. Here, authors observed trichoscopic
      patterns and evaluated their importance in the diagnosis of TTM. MATERIALS AND
      METHODS: This study was conducted in S. Nijalingappa Medical College, Bagalkot,
      from January 2014 to July 2014. Ten patients with clinically suspected TTM were
      included in the study. Informed consent was taken and ethical clearance was
      obtained. Dermlite3 dermoscope was used with Sony camera attachment to save the
      images. Histopathological examination was conducted in all the patients to
      confirm the diagnosis. RESULTS: Ten patients were included in the study. Mean age
      of the patients was 34 years. Most common symptom was patchy loss of hair in the
      frontal area (100%). Common trichoscopic feature was decreased hair density and
      broken hairs. Trichoptilosis (split ends) and irregular coiled hairs were seen in
      80% patients. Novel diagnostic signs like black dots, flame hair, v-sign,
      follicular hemorrhages, were seen in 30% each. Tulip hair and hair powder were
      observed in 10% of patients. All patients had the noninflammatory alopecia with
      distorted and collapsed inner root sheath in histopathology. CONCLUSION:
      Trichotillomania is often chronic and difficult to treat. Hence, early diagnosis
      and treatment is necessary. Authors believe that the trichoscopy plays a vital
      role in the diagnosis of this condition by demonstrating specific trichoscopic
      patterns.

PMID- 25368472
TI  - Direct immunofluorescence pattern and histopathological staging in alopecia
      areata.
AB  - AIM: The present study was designed to categorize alopecia areata (AA) into
      various stages based on histopathology and further study the direct
      immunofluorescence (DIF) pattern. MATERIALS AND METHODS: The current study is
      noninterventional, prospective study on 25 consecutive patients suspected of AA
      based on clinical assessment. Histomorphologic features and immunoreactivity for
      IgG, IgM, IgA, and C3, was studied on biopsy material. RESULTS: Age of the
      patients ranged from 6 years to 48 years with a mean age of 28.56 +/- 21.8 years.
      Majority of patients, 9 (36%) were in the age group of 21-30 years. Of 25
      patients, 13 (52%) were males and 12 (48%) were females. Male: female ratio was
      1.1:1. On histopathology majority of cases were in subacute stage 9 (36%),
      followed by chronic 7 (28%), acute 5 (20%) and recovery stages 4 (16%). Three
      (12%) of 4 cases showed characteristic swarm of bees appearance. Two (8%) of the
      cases showed presence of giant cells. Increased numbers of catagen hair were seen
      in 12 (48%) cases. Of 25 cases, 9 (36%) cases showed positive DIF with granular
      deposits. The most common immunoreactant was IgG in 7 (28%) cases, followed by
      IgA in 4 (16%), C3 in 6 (24%) and IgM in 3 (12%) cases. Of 9 cases showing
      positive staining, 3 (12%) were in acute stage and 2 (8%) each in subacute,
      chronic and recovery stages. CONCLUSION: The observations further reiterate that
      immune mechanisms play a role in the pathogenesis of AA.

PMID- 25368473
TI  - Complications of hair restoration surgery: a retrospective analysis.
AB  - BACKGROUND: Hair restoration surgery (HRS) is a very promising and sought after
      aesthetic procedure with very few complications. Complications may occur in the
      donor or the recipient area, and it may be due to surgical or idiopathic causes.
      AIM: The aim was to analyze the complications in male patients who underwent HRS
      for androgenetic alopecia (AGA). MATERIALS AND METHODS: We conducted a
      retrospective analysis of male patients who underwent HRS for AGA from December
      2010 to August 2014. Data were collected from the registers, telephonic enquiry
      and electronic mails. All complications during and after surgery, and their
      subjective feeling about hair growth was recorded. RESULTS: Seventy-three
      patients were included in the analysis. A total of 65 patients had undergone
      follicular unit transplant, 7 patients underwent FUE, and one patient had body
      hair transplantation. Postoperative edema was found in 42.47% of patients,
      followed by sterile folliculitis in 23.29% of patients, wide donor scar in 15.07%
      of patients, bacterial folliculitis and numbness/paresthesia in 10.96% of
      patients. Other complications such as raised scar, hiccups, pruritus, excessive
      bleeding were found in isolated cases. CONCLUSION: Thorough preoperative
      evaluation, skillful surgical techniques, good communication and postoperative
      follow-up go a long way in giving satisfactory outcome with fewer complications
      in HRS.

PMID- 25368474
TI  - Perforating pilomatricoma in a 62-year-old female: a rare case report.
AB  - Pilomatricoma presents as a single, slow-growing, painless, superficial mass
      arising from the hair matrix cells, over the hair-bearing areas of the body,
      especially the head and neck. Perforating pilomatricoma is a rare variant of
      pilomatricoma presenting as crusted or ulcerated nodule. Here, we report a case
      of 62-year-old female presenting with rapidly growing noduloulcerative lesion on
      the left cheek, which on histopathology showed perforating pilomatricoma. 

PMID- 25368475
TI  - Seemingly insignificant, but crucial cytomorphological leads in diagnosis of
      pilomatricoma of parotid region.
AB  - Pilomatricoma is a benign cutaneous appendegeal neoplasm which occurs as dermal
      nodule on head and neck region of children and young adults. Tumors pose a
      potential difficulty when diagnosed on fine-needle aspiration cytology. In this
      communication, we illustrate the cytomorphological features of pilomatricoma in a
      38-year-female who presented with a nodule over the parotid region. Repeated
      aspirations of this nodule revealed low cellularity and cytology was hence
      inconclusive. The final diagnosis was made on histological examination and then
      retrospectively when those paucicellular cytological smears were analyzed again;
      showed features that could have driven the pathologist toward pilomatricoma.
      Familiarization and careful cytological examination under appropriate clinical
      conditions is warranted. 

PMID- 25368476
TI  - Imaging of trichoptysis - how a radiologist can help?
AB  - Trichoptysis is a rare symptom, but pathognomonic of a teratoma having a
      bronchial communication. Thoracic teratomas are usually located within the
      anterior mediastinum, but rarely present with trichoptysis, as transpleural
      erosion of a mediastinal teratoma into lung and hence bronchial tree is
      exceedingly rare. We report the characteristic radiological and clinical features
      in one such case with ruptured mature mediastinal teratoma having a bronchial
      communication leading to trichoptysis. Only nine cases of trichoptysis have been
      reported in the literature as yet, but a fistulous communication with the
      bronchial tree on computed tomography, as seen in the present report, has not
      been demonstrated in any of these preceding reports. Histopathological sample
      obtained during the surgery further confirmed the presence of a mediastinal
      teratoma with transpleural broncho-pulmonary communication. 

PMID- 25368477
TI  - Extensive pili multigemini over the back.
AB  - Pili multigemini is a rare disorder where more than one hair exists in a single
      hair follicle. Papillar tips that divide into several tips will produce several
      hair shafts, so that characteristically do not fuse again. This disorder is
      relatively frequent on the beard of adult men and on the scalp of children.
      However, extensive areas of pili multigemini in other locations have rarely been
      described. 

PMID- 25368478
TI  - Marie-unna hereditary hypotrichosis.
AB  - Marie-Unna type of hereditary hypotrichosis is a rare autosomal dominant disorder
      that has a distinctive type of hair loss pattern that varies with child's age. It
      is characterized by sparse or absent hair at birth with regrowth of coarse, wiry
      twisted hair from childhood, followed by progressive loss on approaching puberty.
      We report a 12-year-old male child with characteristic clinical features
      suggestive of hereditary hypotrichosis of Marie-Unna type. 

PMID- 25368479
TI  - An unusual location of a pilar sheath acanthoma.
AB  - Pilar sheath acanthoma is a rare, benign follicular hamartoma that frequently
      presents as an asymptomatic, flesh-colored papule with a central opening. First
      described in 1978 by Mehregan and Brownstein, these lesions generally appear on
      the upper lip of elderly patients. We present an interesting case of a pilar
      sheath acanthoma presenting on the earlobe in a middle-aged male. To the best of
      our knowledge, this is the first reported case of a pilar sheath acanthoma found
      in such a unique location. 

PMID- 25368480
TI  - Woolly hair nevus in a toddler.
AB  - Woolly hair nevus (WHN) is a rare hair condition, with only a few cases reported.
      It affects young children of both sexes and currently, there is no available
      treatment. When WHN is associated with an epidermal nevus, further study is
      required to rule out ophthalmologic and neurologic abnormalities. We present the
      case of a Chilean 3-year-old healthy girl with a WHN, with no other clinical
      findings. This case illustrates a WHN in which the benign and chronic nature of
      the disease must be advised to the parents in order to prevent further concerns. 

PMID- 25368481
TI  - Low-level laser therapy for androgenic alopecia.

PMID- 25368482
TI  - An unusual pattern of alopecia areata.

PMID- 25368484
TI  - Lesionalized therapy beyond personalized therapy in cancer management.

PMID- 25368485
TI  - Practical guidelines for the surgical treatment of gallbladder cancer.
AB  - At present, surgical treatment is the only curative option for gallbladder (GB)
      cancer. Many efforts therefore have been made to improve resectability and the
      survival rate. However, GB cancer has a low incidence, and no randomized,
      controlled trials have been conducted to establish the optimal treatment
      modalities. The present guidelines include recent recommendations based on
      current understanding and highlight controversial issues that require further
      research. For T1a GB cancer, the optimal treatment modality is simple
      cholecystectomy, which can be carried out as either a laparotomy or a
      laparoscopic surgery. For T1b GB cancer, either simple or an extended
      cholecystectomy is appropriate. An extended cholecystectomy is generally
      recommended for patients with GB cancer at stage T2 or above. In extended
      cholecystectomy, a wedge resection of the GB bed or a segmentectomy IVb/V can be
      performed and the optimal extent of lymph node dissection should include the
      cystic duct lymph node, the common bile duct lymph node, the lymph nodes around
      the hepatoduodenal ligament (the hepatic artery and portal vein lymph nodes), and
      the posterior superior pancreaticoduodenal lymph node. Depending on patient
      status and disease severity, surgeons may decide to perform palliative surgeries.

PMID- 25368486
TI  - Changes in the cesarean section rate in Korea (1982-2012) and a review of the
      associated factors.
AB  - Although Cesarean section (CS) itself has contributed to the reduction in
      maternal and perinatal mortality, an undue rise in the CS rate (CSR) has been
      issued in Korea as well as globally. The CSR in Korea increased over the past two
      decades, but has remained at approximately 36% since 2006. Contributing factors
      associated with the CSR in Korea were an improvement in socio-economic status, a
      higher maternal age, a rise in multiple pregnancies, and maternal obesity. We
      found that countries with a no-fault compensation system maintained a lower CSR
      compared to that in countries with civil action, indicating the close
      relationship between the CSR and the medico-legal system within a country. The
      Korean government has implemented strategies including an incentive system
      relating to the CSR or encouraging vaginal birth after Cesarean to decrease CSR,
      but such strategies have proved ineffective. To optimize the CSR in Korea,
      efforts on lowering the maternal childbearing age or reducing maternal obesity
      are needed at individual level. And from a national view point, reforming health
      care system, which could encourage the experienced obstetricians to be trained
      properly and be relieved from legal pressure with deliveries is necessary. 

PMID- 25368487
TI  - Impact of ENPP1 K121Q on change of insulin resistance after web-based
      intervention in Korean men with diabetes and impaired fasting glucose.
AB  - Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been
      studied in relation to type 2 diabetes mellitus (T2DM) and insulin resistance
      (IR). We hypothesized that the difference in genotype may be one of the factors
      that affect the outcome of intervention. We genotyped 448 men with fasting
      glucose>=5.6 mM/L, including 371 in subjects with K allele (KK) (69 control group
      [CG]; and 302 intervention group [IG]) and 77 in subjects with Q allele (KQ+QQ)
      (13 CG and 64 IG). The web-based intervention based on a lifestyle modification
      was delivered by e-mail once a month for 10 months. In the KK, IG demonstrated
      significantly decreased levels of fasting serum insulin (FSI) as compared to CG
      and homeostasis model of assessment of insulin resistance (HOMA-IR). In the KQ+QQ
      IG group, hemoglobin A1c (HbA1c), FSI and HOMA-IR were significantly decreased,
      and showed further reduction in the HOMA-IR than KQ+QQ CG. After analysis of
      covariance, K121Q did significantly influence the change of HbA1c in CG after
      appropriate adjustment. In a multivariate model, BMI change predicted HOMA-IR
      change (adjusted beta=0.801; P=0.022) in KK IG subjects with T2DM. ENPP1 K121Q
      did not influence the change in IR. However, individuals with T2DM carrying the
      K121 variant are very responsive to the effect of BMI reduction on HOMA-IR. 

PMID- 25368488
TI  - Optimal tailored screening protocol after living donor liver transplantation for
      hepatocellular carcinoma.
AB  - The indication for hepatocellular carcinoma (HCC) is expanding in living donor
      liver transplantation (LDLT). Early detection and effective management of
      recurrence has become an important issue in LDLT for HCC. This study aimed to
      find an optimal screening protocol in terms of screening interval and screening
      tools by analyzing recurrence pattern after LDLT for HCC. A total of 205 LDLT
      patients in two centers from February 1999 to October 2010 was reviewed.
      Recurrence appeared in 55 cases. Six risk factors for recurrence were identified:
      preoperative alpha-fetoprotein >400, Edmonson grade 3 or 4, tumor size >7 cm,
      tumor number >=7, minimal tumor necrosis in the transarterial chemoembolization
      group and positive micro-vascular invasion. Four groups with different ranges of
      index scores showed different recurrence-free survival and median time to
      recurrence. Group I showed low and late recurrence. Groups II and III showed
      linearly increased rate of recurrence until 18 months. Group IV showed very early
      recurrence within 6 months. Across the groups, extra-hepatic recurrence developed
      in more than 40% of cases and multi-organ recurrence rate was 20%. The screening
      interval should be different based on the risk of recurrence. Screening should
      include work-up for extra-hepatic recurrence as well as intra-hepatic recurrence.

PMID- 25368489
TI  - Detection of Cryptosporidium parvum in environmental soil and vegetables.
AB  - Cryptosporidium parvum is a zoonotic protozoan parasite that causes
      cryptosporidial enteritis. Numerous outbreaks of cryptosporidiosis have been
      reported worldwide. Cryptosporidium is transmitted to hosts via consumption of
      contaminated water and food but also by direct contact with contaminated soil or
      infected hosts. The present study investigated farm soil collected from 34
      locations along the western Korean peninsula and 24 vegetables purchased from
      local grocery markets in Seoul. The soil and vegetable samples were examined by
      real-time polymerase chain reaction (qPCR) to estimate the risk of infection.
      Eleven of 34 locations (32.4%) and 3 of 24 vegetable samples (12.5%) were
      contaminated with Cryptosporidium parvum, as confirmed by TaqI enzyme digestion
      of qPCR products and DNA sequencing. It is suggested that Cryptosporidium
      infection can be mediated via farm soil and vegetables. Therefore, it is
      necessary to reduce contamination of this organism in view of public health. 

PMID- 25368490
TI  - The effect of probiotics for preventing radiation-induced morphological changes
      in intestinal mucosa of rats.
AB  - Radiation therapy is an important treatment modality for abdominal or pelvic
      cancer, but there is a common and serious complication such as radiation-induced
      enteritis. Probiotics is reported to have positive effects against radiation
      induced enteropathy. In this study, morphological changes of bowel mucosa were
      analyzed in rats to presume the effect of probiotics on radiation-induced
      enteritis and its correlation with radiation dose. A total of 48 adult male
      Sprague-Dawley rats were randomly assigned to two groups and received a solution
      containing 1.0*10(8) colony-forming units of Lactiobacillus acidophilus or water
      once daily for 10 days. Each of two groups was divided into three subgroups and
      abdomino-pelvic area of each subgroup was irradiated with 10, 15, and 20 Gy,
      respectively on the seventh day of feeding the solutions. All rats were
      sacrificed 3 days after irradiation and the mucosal thickness and villus height
      of jejunum, ileum and colon were measured. The morphological parameters of the
      small intestine represented significant differences between two solution groups
      irradiated 10 or 15 Gy, except for villus height of jejunum in 15 Gy-subgroup
      (P=0.065). There was no significant morphometric difference between two groups
      irradiated with 20 Gy of radiation. Probiotics appear to be effective for the
      morphological shortening of small intestinal mucosa damaged by radiation less
      than or equal to 15 Gy. 

PMID- 25368491
TI  - Gender differences in the association between serum gamma-glutamyltransferase and
      blood pressure change: a prospective community-based cohort study.
AB  - We evaluated the gender differences in the relation of baseline serum gamma
      glutamyltransferase (GGT) levels to blood pressure (BP) change during 4 yr. 4,025
      normotensive subjects (1,945 men and 2,080 women) who aged 40-69 yr at baseline
      participated in the Ansung-Ansan cohort of the Korean Genome Epidemiology Study
      were included. The associations of GGT with baseline BP or 4-yr change of BP were
      evaluated. GGT levels were associated with systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) at baseline after adjusting for age, body mass
      index (BMI), HDL-cholesterol, triglyceride, C-reactive protein (CRP), current
      smoking status and alcohol intake (SBP, beta=1.28, P<0.001; DBP, beta=1.41,
      P<0.001). GGT levels were also associated with 4-yr change in BP after adjusting
      for age, BMI, HDL-cholesterol, triglyceride, CRP, current smoking status, alcohol
      intake and SBP (SBP, beta=1.08, P=0.001; DBP, beta=0.64, P=0.003). This
      association was statistically significant in men (SBP, beta=1.82, P<0.001; DBP,
      beta=1.05, P=0.001), but not in women (SBP, beta=0.38, P=0.466; DBP, beta=-0.37,
      P=0.304). Remarkably, this association between GGT and BP was significant in men
      at 40-49 yr of age. In summary, we found positive associations between GGT levels
      at baseline and the change of BP. The relation of GGT level and the change of BP
      was only significant in men, not in women, which warrants further studies to
      elucidate the biologic mechanisms. 

PMID- 25368492
TI  - Association between adipokines and coronary artery lesions in children with
      Kawasaki Disease.
AB  - Body fat is an important source of adipokine, which is associated with energy
      balance and inflammatory and immune responses. However, the role of adipokines in
      coronary artery complications in Kawasaki disease (KD) has not yet been fully
      explained. We investigated whether serum adipokine level can be a useful marker
      for patients with KD who are at higher risk of developing coronary artery lesion
      (CAL). We measured adipokine levels and other inflammatory parameters in 40
      patients with KD, 32 febrile controls, and 15 afebrile controls. Interleukin (IL)
      6, tumor necrosis factor (TNF)-alpha and other laboratory parameters were also
      measured before and after intravenous immunoglobulin therapy, and in the
      convalescent phase. At admission, the serum resistin levels in KD children were
      significantly higher than those in controls (177.56 ng/mL in KD children, 76.48
      ng/mL in febrile controls, and 17.95 ng/mL in afebrile controls). In patients
      with KD, resistin levels were significantly associated with decreased hemoglobin
      levels (P=0.049) and increased IL-6 levels (P=0.014). The serum IL-6 levels were
      significantly higher and body mass index was significantly lower in the group of
      KD with CALs than those without CALs (228.26 ng/mL vs. 39.18 ng/mL and 15.09 vs.
      16.60, respectively). In conclusion, resistin is significantly elevated in KD
      patients, although it has no prognostic value of predicting coronary artery
      lesion in the acute stage. 

PMID- 25368493
TI  - Impact of Framingham risk score, flow-mediated dilation, pulse wave velocity, and
      biomarkers for cardiovascular events in stable angina.
AB  - Although the age-adjusted Framingham risk score (AFRS), flow-mediated dilation
      (FMD), brachial-ankle pulse wave velocity (baPWV), high-sensitivity C-reactive
      protein (hsCRP), fibrinogen, homocysteine, and free fatty acid (FFA) can predict
      future cardiovascular events (CVEs), a comparison of these risk assessments for
      patients with stable angina has not been reported. We enrolled 203 patients with
      stable angina who had been scheduled for coronary angiography (CAG). After CAG,
      134 patients showed significant coronary artery disease. During 4.2 yr follow-up,
      36 patients (18%) showed CVEs, including myocardial infarction, de-novo coronary
      artery revascularization, in-stent restenosis, stroke, and cardiovascular death.
      ROC analysis showed that AFRS, FMD, baPWV, and hsCRP could predict CVEs (with AUC
      values of 0.752, 0.707, 0.659, and 0.702, respectively, all P<0.001 except baPWV
      P=0.003). A Cox proportional hazard analysis showed that AFRS and FMD were
      independent predictors of CVEs (HR, 2.945; 95% CI, 1.572-5.522; P=0.001 and HR,
      0.914; 95% CI, 0.826-0.989; P=0.008, respectively). However, there was no
      difference in predictive power between combining AFRS plus FMD and AFRS alone
      (AUC 0.752 vs. 0.763; z=1.358, P=0.175). In patients with stable angina, AFRS and
      FMD are independent predictors of CVEs. However, there is no additive value of
      FMD on the AFRS in predicting CVEs. 

PMID- 25368494
TI  - Application of lidocaine jelly on chest tubes to reduce pain caused by drainage
      catheter after coronary artery bypass surgery.
AB  - The objective of this study was to assess the effect of lidocaine jelly
      application to chest tubes on the intensity and duration of overall pain, chest
      tube site pain and the required analgesics for postoperative pain relief in
      coronary artery bypass graft (CABG) patients. For patients in group L, we applied
      sterile 2% lidocaine jelly on the chest tubes just before insertion, and for
      patients in group C, we applied normal saline. Overall visual analogue scale
      (VAS), maximal pain area with their VAS were documented postoperatively, and the
      frequency that button of patient-controlled analgesia was pressed (FPB) and total
      fentanyl consumption were assessed. The number of patients who complained that
      tube site was the most painful site was significantly higher in group C than in
      group L (85% vs. 30% at extubation, P<0.001). The overall VAS score was
      significantly higher in group C than in group L (39.14+/-12.49 vs. 27.74+/-13.76
      at extubation, P=0.006). After all of the tubes were removed, the VAS score
      decreased more in group C (5.74+/-4.77, P<0.001) than in group L (3.05+/-2.48,
      P<0.001). FPB and total fentanyl consumption were significantly higher in group C
      than in group L (73.00, 59.00-78.00 vs. 34.00, 31.00-39.25, P<0.001; 2,214.65+/
      37.01 vs. 1,720.19+/-361.63, P<0.001, respectively). Lidocaine jelly application
      is a very simple way to reduce postoperative pain by reducing chest tube site
      pain after CABG. (Clinical Trials Registry No. ACTRN 12611001215910). 

PMID- 25368495
TI  - Efficacy of bronchoscopic lung volume reduction by endobronchial valves in
      patients with heterogeneous emphysema: report on the first Asian cases.
AB  - Although many patients with severe emphysema have benefited from bronchoscopic
      lung volume reduction (BLVR) worldwide, experience of BLVR in Asian emphysema
      patients is scarce. Between July 2012 and March 2013, seven patients with
      advanced heterogeneous emphysema underwent BLVR in the Asan Medical Center. They
      had severe dyspnea and poor lung function (Modified Medical Research Council
      dyspnea scale 3-4; median forced expiratory volume in 1 sec [FEV1], 0.59 L [19.0
      % predicted]; median 6-min walk distance [6MWD], 195 m). Endobronchial valves
      were inserted into the target lobe which was most hyperinflated and least
      perfused, and had no collateral ventilation with other lobes. Six patients showed
      clinical improvement after 1 month. Of them, 2 patients improved to dyspnea scale
      1 and 4 patients did to scale 2 (P = 0.026). The median FEV1 increased from 0.59
      to 0.89 L (51%; P = 0.028) and the median 6MWD increased from 195 to 252 m
      (29.2%; P = 0.028). Two patients developed a pneumothorax (one requiring
      drainage) and one patient experienced slight hemoptysis; however, there were no
      other serious adverse events. BLVR is effective in Asian advanced emphysema
      patients, with noted clinical improvements in lung function and exercise
      capacity. 

PMID- 25368496
TI  - Rebleeding after initial endoscopic hemostasis in peptic ulcer disease.
AB  - Endoscopic hemostasis is the first-line treatment for upper gastrointestinal
      bleeding (UGIB). Although several factors are known to be risk factors for
      rebleeding, little is known about the use of antithrombotics. We tried to verify
      whether the use of antithrombotics affects rebleeding rate after a successful
      endoscopic hemostasis for peptic ulcer disease (PUD). UGIB patients who underwent
      successful endoscopic hemostasis were included. Rebleeding was diagnosed when the
      previously treated lesion bled again within 30 days of the initial episode. Of
      522 UGIB patients with PUD, rebleeding occurred in 93 patients (17.8%). The rate
      of rebleeding was higher with aspirin medication (P=0.006) and after a long
      endoscopic hemostasis (P<0.001). Of all significant variables, procedure time
      longer than 13.5 min was related to the rate of rebleeding (OR, 2.899; 95% CI,
      1.768-4.754; P<0.001) on the logistic regression analysis. The rate of rebleeding
      after endoscopic hemostasis for PUD is higher in the patients after a long
      endoscopic hemostasis. Endoscopic hemostasis longer than 13.5 min is related to
      rebleeding after a successful endoscopic hemostasis for PUD. 

PMID- 25368497
TI  - Neural substrates of Hanja (Logogram) and Hangul (Phonogram) character readings
      by functional magnetic resonance imaging.
AB  - The two basic scripts of the Korean writing system, Hanja (the logography of the
      traditional Korean character) and Hangul (the more newer Korean alphabet), have
      been used together since the 14th century. While Hanja character has its own
      morphemic base, Hangul being purely phonemic without morphemic base. These two,
      therefore, have substantially different outcomes as a language as well as
      different neural responses. Based on these linguistic differences between Hanja
      and Hangul, we have launched two studies; first was to find differences in
      cortical activation when it is stimulated by Hanja and Hangul reading to support
      the much discussed dual-route hypothesis of logographic and phonological routes
      in the brain by fMRI (Experiment 1). The second objective was to evaluate how
      Hanja and Hangul affect comprehension, therefore, recognition memory,
      specifically the effects of semantic transparency and morphemic clarity on memory
      consolidation and then related cortical activations, using functional magnetic
      resonance imaging (fMRI) (Experiment 2). The first fMRI experiment indicated
      relatively large areas of the brain are activated by Hanja reading compared to
      Hangul reading. The second experiment, the recognition memory study, revealed two
      findings, that is there is only a small difference in recognition memory for
      semantic transparency, while for the morphemic clarity was much larger between
      Hanja and Hangul. That is the morphemic clarity has significantly more effect
      than semantic transparency on recognition memory when studies by fMRI in
      correlation with behavioral study. 

PMID- 25368498
TI  - Prevalence of osteoporosis in female patients with advanced knee osteoarthritis
      undergoing total knee arthroplasty.
AB  - This study sought to demonstrate bone mineral density (BMD) conditions in elderly
      female patients with knee osteoarthritis (OA) undergoing total knee arthroplasty
      (TKA). In addition, we sought to determine whether their BMD conditions differ
      from those of community-based females without knee OA. Finally we sought to
      determine whether clinical statuses are related to BMD in the knee OA patients.
      BMD conditions in 347 female patients undergoing TKA and 273 community-based
      females were evaluated. Additionally, comparative analyses of BMD between age and
      body mass index-matched knee OA groups (n=212) and the control groups (n=212)
      were performed. In the pre-matched knee OA group, regression analyses were
      performed to determine whether preoperative clinical statuses were related to
      BMD. Considerable prevalence of coexistent osteoporosis (31%) was found in the
      pre-matched knee OA patients undergoing TKA. We found no significant differences
      of the BMD T-scores and the prevalence of osteoporosis between the age and body
      mass index-matched knee OA and control groups. In the pre-matched knee OA
      patients, poorer preoperative clinical scores were related to poorer BMD T-scores
      in the proximal femur and/or lumbar spine. Our study suggests that more attention
      should be paid to identify and treat osteoporosis in elderly female patients with
      advanced knee OA undergoing TKA. 

PMID- 25368499
TI  - Metastasis of colon cancer to medullary thyroid carcinoma: a case report.
AB  - Metastasis to the primary thyroid carcinoma is extremely rare. We report here a
      case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53
      yr old man with a history of colon cancer. He showed a nodular lesion, suggesting
      malignancy in the thyroid gland, in a follow-up examination after colon cancer
      surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor
      cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The
      patient underwent a total thyroidectomy. Using several specific
      immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma
      metastasis to MTC. To the best of our knowledge, the present patient is the first
      case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor
      metastasis to primary thyroid carcinoma is very rare, we still should consider
      metastasis to the thyroid gland, when a patient with a history of other
      malignancy presents with a new thyroid finding. 

PMID- 25368500
TI  - Re: cancer risk in adult residents near nuclear power plants in Korea: a cohort
      study of 1992-2010.

PMID- 25368501
TI  - Why double-blind review is preferable for scholarly journals.

PMID- 25368504
TI  - Research Workforce Diversity: The Case of Balancing National versus International
      Postdocs in US Biomedical Research.
AB  - The US government has been increasingly supporting postdoctoral training in
      biomedical sciences to develop the domestic research workforce. However, current
      trends suggest that mostly international researchers benefit from the funding,
      many of whom might leave the USA after training. In this paper, we describe a
      model used to analyse the flow of national versus international researchers into
      and out of postdoctoral training. We calibrate our model in the case of the USA
      and successfully replicate the data. We use the model to conduct simulation-based
      analyses of effects of different policies on the diversity of postdoctoral
      researchers. Our model shows that capping the duration of postdoctoral careers, a
      policy proposed previously, favours international postdoctoral researchers. The
      analysis suggests that the leverage point to help the growth of domestic research
      workforce is in the pregraduate education area, and many policies implemented at
      the postgraduate level have minimal or unintended effects on diversity.

PMID- 25368505
TI  - Automated recommendation for cervical cancer screening and surveillance.
AB  - Because of the complexity of cervical cancer prevention guidelines, clinicians
      often fail to follow best-practice recommendations. Moreover, existing clinical
      decision support (CDS) systems generally recommend a cervical cytology every
      three years for all female patients, which is inappropriate for patients with
      abnormal findings that require surveillance at shorter intervals. To address this
      problem, we developed a decision tree-based CDS system that integrates national
      guidelines to provide comprehensive guidance to clinicians. Validation was
      performed in several iterations by comparing recommendations generated by the
      system with those of clinicians for 333 patients. The CDS system extracted
      relevant patient information from the electronic health record and applied the
      guideline model with an overall accuracy of 87%. Providers without CDS assistance
      needed an average of 1 minute 39 seconds to decide on recommendations for
      management of abnormal findings. Overall, our work demonstrates the feasibility
      and potential utility of automated recommendation system for cervical cancer
      screening and surveillance. 

PMID- 25368503
TI  - Circadian Rhythm Sleep Disorders.
AB  - OBJECTIVE: To review circadian rhythm sleep disorders, including underlying
      causes, diagnostic considerations, and typical treatments. METHODS: Literature
      review and discussion of specific cases. RESULTS: Survey studies 1,2 suggest that
      up to 3% of the adult population suffers from a circadian rhythm sleep disorder
      (CRSD). However, these sleep disorders are often confused with insomnia, and an
      estimated 10% of adult and 16% of adolescent sleep disorders patients may have a
      CRSD 3-6. While some CRSD (such as jet lag) can be self-limiting, others when
      untreated can lead to adverse medical, psychological, and social consequences.
      The International Classification of Sleep Disorders classifies CRSD as
      dyssomnias, with six subtypes: Advanced Sleep Phase Type, Delayed Sleep Phase
      Type, Irregular Sleep Wake Type, Free Running Type, Jet Lag Type, and Shift Work
      Type. The primary clinical characteristic of all CRSD is an inability to fall
      asleep and wake at the desired time. It is believed that CRSD arise from a
      problem with the internal biological clock (circadian timing system) and/or
      misalignment between the circadian timing system and the external 24-hour
      environment. This misalignment can be the result of biological and/or behavioral
      factors. CRSD can be confused with other sleep or medical disorders. CONCLUSIONS:
      Circadian rhythm sleep disorders are a distinct class of sleep disorders
      characterized by a mismatch between the desired timing of sleep and the ability
      to fall asleep and remain asleep. If untreated, CRSD can lead to insomnia and
      excessive daytime sleepiness, with negative medical, psychological, and social
      consequences. It is important for physicians to recognize potential circadian
      rhythm sleep disorders so that appropriate diagnosis, treatment, and referral can
      be made.

PMID- 25368506
TI  - Quality Control for RNA-Seq (QuaCRS): An Integrated Quality Control Pipeline.
AB  - QuaCRS (Quality Control for RNA-Seq) is an integrated, simplified quality control
      (QC) system for RNA-seq data that allows easy execution of several open-source QC
      tools, aggregation of their output, and the ability to quickly identify quality
      issues by performing meta-analyses on QC metrics across large numbers of samples
      in different studies. It comprises two main sections. First is the QC Pack
      wrapper, which executes three QC tools: FastQC, RNA-SeQC, and selected functions
      from RSeQC. Combining these three tools into one wrapper provides increased ease
      of use and provides a much more complete view of sample data quality than any
      individual tool. Second is the QC database, which displays the resulting metrics
      in a user-friendly web interface. It was designed to allow users with less
      computational experience to easily generate and view QC information for their
      data, to investigate individual samples and aggregate reports of sample groups,
      and to sort and search samples based on quality. The structure of the QuaCRS
      database is designed to enable expansion with additional tools and metrics in the
      future. The source code for not-for-profit use and a fully functional sample user
      interface with mock data are available at http://bioserv.mps.ohio
      state.edu/QuaCRS/. 

PMID- 25368507
TI  - Network-based Prediction of Cancer under Genetic Storm.
AB  - Classification of cancer patients using traditional methods is a challenging task
      in the medical practice. Owing to rapid advances in microarray technologies,
      currently expression levels of thousands of genes from individual cancer patients
      can be measured. The classification of cancer patients by supervised statistical
      learning algorithms using the gene expression datasets provides an alternative to
      the traditional methods. Here we present a new network-based supervised
      classification technique, namely the NBC method. We compare NBC to five
      traditional classification techniques (support vector machines (SVM), k-nearest
      neighbor (kNN), naive Bayes (NB), C4.5, and random forest (RF)) using 50-300
      genes selected by five feature selection methods. Our results on five large
      cancer datasets demonstrate that NBC method outperforms traditional
      classification techniques. Our analysis suggests that using symmetrical
      uncertainty (SU) feature selection method with NBC method provides the most
      accurate classification strategy. Finally, in-depth analysis of the correlation
      based co-expression networks chosen by our network-based classifier in different
      cancer classes shows that there are drastic changes in the network models of
      different cancer types. 

PMID- 25368508
TI  - Master regulators, regulatory networks, and pathways of glioblastoma subtypes.
AB  - Glioblastoma multiforme (GBM) is the most common malignant brain tumor. GBM
      samples are classified into subtypes based on their transcriptomic and epigenetic
      profiles. Despite numerous studies to better characterize GBM biology, a
      comprehensive study to identify GBM subtype- specific master regulators, gene
      regulatory networks, and pathways is missing. Here, we used FastMEDUSA to compute
      master regulators and gene regulatory networks for each GBM subtype. We also ran
      Gene Set Enrichment Analysis and Ingenuity Pathway Analysis on GBM expression
      dataset from The Cancer Genome Atlas Project to compute GBM- and GBM subtype
      specific pathways. Our analysis was able to recover some of the known master
      regulators and pathways in GBM as well as some putative novel regulators and
      pathways, which will aide in our understanding of the unique biology of GBM
      subtypes. 

PMID- 25368509
TI  - Network Analysis of Cancer-focused Association Network Reveals Distinct Network
      Association Patterns.
AB  - Cancer is a complex and heterogeneous disease. Genetic methods have uncovered
      thousands of complex tissue-specific mutation-induced effects and identified
      multiple disease gene targets. Important associations between cancer and other
      biological entities (eg, genes and drugs) in cancer network, however, are usually
      scattered in biomedical publications. Systematic analyses of these cancer
      specific associations can help highlight the hidden associations between
      different cancer types and related genes/drugs. In this paper, we proposed a
      novel network-based computational framework to identify statistically over
      expressed subnetwork patterns called network motifs (NMs) in an integrated cancer
      specific drug-disease-gene network extracted from Semantic MEDLINE, a database
      containing extracted associations from MEDLINE abstracts. Eight significant NMs
      were identified and considered as the backbone of the cancer association network.
      Each NM corresponds to specific biological meanings. We demonstrated that such
      approaches will facilitate the formulization of novel cancer research hypotheses,
      which is critical for translational medicine research and personalized medicine
      in cancer. 

PMID- 25368510
TI  - Developing a comprehensive database management system for organization and
      evaluation of mammography datasets.
AB  - We aimed to design and develop a comprehensive mammography database system (CMDB)
      to collect clinical datasets for outcome assessment and development of decision
      support tools. A Health Insurance Portability and Accountability Act (HIPAA)
      compliant CMDB was created to store multi-relational datasets of demographic risk
      factors and mammogram results using the Breast Imaging Reporting and Data System
      (BI-RADS) lexicon. The CMDB collected both biopsy pathology outcomes, in a breast
      pathology lexicon compiled by extending BI-RADS, and our institutional breast
      cancer registry. The audit results derived from the CMDB were in accordance with
      Mammography Quality Standards Act (MQSA) audits and national benchmarks. The CMDB
      has managed the challenges of multi-level organization demanded by the complexity
      of mammography practice and lexicon development in pathology. We foresee that the
      CMDB will be useful for efficient quality assurance audits and development of
      decision support tools to improve breast cancer diagnosis. Our procedure of
      developing the CMDB provides a framework to build a detailed data repository for
      breast imaging quality control and research, which has the potential to augment
      existing resources. 

PMID- 25368511
TI  - StickWRLD as an Interactive Visual Pre-Filter for Canceromics-Centric Expression
      Quantitative Trait Locus Data.
AB  - As datasets increase in complexity, the time required for analysis (both
      computational and human domain-expert) increases. One of the significant
      impediments introduced by such burgeoning data is the difficulty in knowing what
      features to include or exclude from statistical models. Simple tables of summary
      statistics rarely provide an adequate picture of the patterns and details of the
      dataset to enable researchers to make well-informed decisions about the adequacy
      of the models they are constructing. We have developed a tool, StickWRLD, which
      allows the user to visually browse through their data, displaying all possible
      correlations. By allowing the user to dynamically modify the retention parameters
      (both P and the residual, r), StickWRLD allows the user to identify significant
      correlations and disregard potential correlations that do not meet those same
      criteria - effectively filtering through all possible correlations quickly and
      identifying possible relationships of interest for further analysis. In this
      study, we applied StickWRLD to a semi-synthetic dataset constructed from two
      published human datasets. In addition to detecting high-probability correlations
      in this dataset, we were able to quickly identify gene-SNP correlations that
      would have gone undetected using more traditional approaches due to issues of low
      penetrance. 

PMID- 25368512
TI  - Clear-cornea cataract surgery: pupil size and shape changes, along with anterior
      chamber volume and depth changes. A Scheimpflug imaging study.
AB  - PURPOSE: To investigate, by high-precision digital analysis of data provided by
      Scheimpflug imaging, changes in pupil size and shape and anterior chamber (AC)
      parameters following cataract surgery. PATIENTS AND METHODS: The study group (86
      eyes, patient age 70.58+/-10.33 years) was subjected to cataract removal surgery
      with in-the-bag intraocular lens implantation (pseudophakic). A control group of
      75 healthy eyes (patient age 51.14+/-16.27 years) was employed for comparison.
      Scheimpflug imaging (preoperatively and 3 months postoperatively) was employed to
      investigate central corneal thickness, AC depth, and AC volume. In addition, by
      digitally analyzing the black-and-white dotted line pupil edge marking in the
      Scheimpflug "large maps," the horizontal and vertical pupil diameters were
      individually measured and the pupil eccentricity was calculated. The correlations
      between AC depth and pupil shape parameters versus patient age, as well as the
      postoperative AC and pupil size and shape changes, were investigated. RESULTS:
      Compared to preoperative measurements, AC depth and AC volume of the pseudophakic
      eyes increased by 0.99+/-0.46 mm (39%; P<0.001) and 43.57+/-24.59 mm(3) (36%;
      P<0.001), respectively. Pupil size analysis showed that the horizontal pupil
      diameter was reduced by -0.27+/-0.22 mm (-9.7%; P=0.001) and the vertical pupil
      diameter was reduced by -0.32+/-0.24 mm (-11%; P<0.001). Pupil eccentricity was
      reduced by -39.56%; P<0.001. CONCLUSION: Cataract extraction surgery appears to
      affect pupil size and shape, possibly in correlation to AC depth increase. This
      novel investigation based on digital analysis of Scheimpflug imaging data
      suggests that the cataract postoperative photopic pupil is reduced and more
      circular. These changes appear to be more significant with increasing patient
      age.

PMID- 25368513
TI  - A simple rescue maneuver for unfolding and centering a tightly rolled graft in
      Descemet membrane endothelial keratoplasty.
AB  - A 74-year-old man underwent Descemet membrane endothelial keratoplasty (DMEK) for
      endothelial decompensation due to Fuchs endothelial dystrophy. After
      descemetorhexis, the DMEK graft was inserted into the anterior chamber. However,
      unfolding of the graft was not possible as the graft was very tightly rolled
      together and the anterior chamber deep. After placing a 30G-cannula connected to
      an air-filled syringe inside the roll's lumen, a small air bubble was injected,
      which allowed the roll to open up, until it assumed a "taco" configuration around
      the bubble. Then, the graft was centered by pressing the posterior part of the
      roll against, and sweeping it over the iris. In the present case a "tight" DMEK
      roll was successfully unfolded by injection of a single air bubble into the
      roll's lumen and centered by a "sweeping" the partialy unfolded graft over the
      iris. This technique allowed a controlled unfolding and centering of the DMEK
      graft with limited trauma to the donor endothelium and may be applied in cases
      where other less traumatic maneuvers are not successful. 

PMID- 25368515
TI  - Determinants of patient satisfaction with hospital health care in psychiatry:
      results based on the SATISPSY-22 questionnaire.
AB  - BACKGROUND: The aim of our study was to identify patient- and care-related
      factors that are associated with patients' satisfaction with psychiatric hospital
      care, using a specific, self-administered questionnaire based exclusively on the
      patient's point of view: the Satisfaction with Psychiatry Care Questionnaire-22
      (SATISPSY-22). METHODS: This cross-sectional study was conducted in the
      psychiatric departments of two French public university teaching hospitals. The
      data collected included sociodemographic information, clinical characteristics,
      care characteristics, and the SATISPSY-22. A multivariate analysis using multiple
      linear regressions was performed to determine the variables potentially
      associated with satisfaction levels. RESULTS: Two hundred seventy patients were
      enrolled in our study. Only one moderate association was found between
      satisfaction and sociodemographic characteristics: the personal experience
      dimension with age (beta=0.15). Clinical improvement was moderately associated
      with higher global satisfaction (beta=-0.15), higher satisfaction with quality of
      care (beta=-0.19), and higher satisfaction with food (beta=-0.18). Stronger
      associations with satisfaction were found for care characteristics, particularly
      the therapeutic alliance with all of the satisfaction dimensions (beta, 0.20
      0.43) except food, and for seclusion with global satisfaction (beta=-0.33) and
      personal experience (beta=-0.32). Patients with previous hospitalization also had
      a higher level of satisfaction with quality of care compared with patients who
      were admitted for the first time (beta=-0.15). CONCLUSION: This study has
      identified a number of potential determinants of satisfaction. The therapeutic
      relationship and seclusion were the most important features associated with a
      patient's satisfaction. These factors might be amenable through intervention,
      which, in turn, might be expected to improve satisfaction, patients' management,
      and health outcomes in psychiatric hospitals.

PMID- 25368516
TI  - An exploration of the choices of patients with chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a progressive loss of renal function
      over a period of time. It is common, often unrecognized, and frequently coexists
      with other conditions, including diabetes and cardiovascular disease. There has
      been little research undertaken into treatment options and decision-making
      processes of CKD patients in general. OBJECTIVES: To determine the treatment
      options that CKD patients are offered and their views and experiences with regard
      to these choices. DESIGN: A survey design was adopted. PARTICIPANTS: Participants
      included patients who had CKD at the time of the study and who were on renal
      dialysis. RESULTS: A wide range of findings emerged from the study. Key findings
      showed that the majority of patients felt that written information was the main
      source of information, but that almost one-quarter of patients felt that they did
      not receive enough information about dialysis to allow them to make an informed
      choice. Almost one-fifth of participants did not consider that they had been
      strongly encouraged by health professionals to be independent with regard to
      their choice of dialysis. CONCLUSION: While the majority of patients feel fully
      informed and involved in the decision-making processes around treatment and
      management of their CKD, not all patients receive sufficient information to make
      an informed choice about their treatment and that treatment options are not
      always presented to patients and their families to enable them to make a fully
      informed choice.

PMID- 25368514
TI  - Safety and efficacy of peramivir for influenza treatment.
AB  - OBJECTIVE: This report presents a review of the efficacy and safety of peramivir,
      a neuraminidase inhibitor that was granted Emergency Use Authorization by the US
      Food and Drug Administration (FDA) from October 23, 2009 to June 23, 2010 during
      the 2009 H1N1 pandemic. METHODS: Literature was accessed via PubMed (January 2000
      April 2014) using several search terms: peramivir; BCX-1812; RWJ 270201; H1N1,
      influenza; antivirals; and neuraminidase inhibitors. The peramivir manufacturers,
      Shionogi and Co Ltd and BioCryst Pharmaceuticals, were contacted to obtain
      unpublished data and information presented at recent scientific meetings.
      Information was obtained from the Centers for Disease Control and Prevention
      (CDC) and from US FDA websites. English-language and Japanese-language reports in
      the literature were reviewed and selected based on relevance, along with
      information from the CDC, US FDA, and the drug manufacturers. RESULTS: We
      obtained eleven clinical trial reports of intravenous peramivir, two of which
      described comparisons with oseltamivir. Seven of nine other recently reported
      published studies was a dose-response study. Clinical reports of critically ill
      patients and pediatric patients infected with pandemic H1N1 described that early
      treatment significantly decreased mortality. Peramivir administered at 300 mg
      once daily in adult patients with influenza significantly reduces the time to
      alleviation of symptoms or fever compared to placebo. It is likely to be as
      effective as other neuraminidase inhibitors. CONCLUSION: Although peramivir shows
      efficacy for the treatment of seasonal and pH1N1 influenza, it has not received
      US FDA approval. Peramivir is used safely and efficiently in hospitalized adult
      and pediatric patients with suspected or laboratory-confirmed influenza.
      Peramivir might be a beneficial alternative antiviral treatment for many
      patients, including those unable to receive inhaled or oral neuraminidase
      inhibitors, or those requiring nonintravenous drug delivery.

PMID- 25368517
TI  - Patients' compliance with different administration routes for allergen
      immunotherapy in Germany.
AB  - BACKGROUND: Allergen immunotherapy (AIT) is the practice of administering
      gradually increasing quantities of an allergen extract to an allergic subject to
      ameliorate the symptoms associated with the subsequent exposure to the causative
      allergen. It is the only treatment that may alter the natural course of allergic
      diseases. According to AIT guidelines and summary of product characteristics
      (SmPCs), the treatment should be carried out for at least 3 years. It is
      controversially discussed whether subcutaneous or sublingual administration
      routes cause higher patients' compliance. METHODS: German sales data for
      different preparations of the allergen manufacturer Allergopharma GmbH & Co. KG
      were retrospectively evaluated for 5 consecutive years, based on prescriptions
      per patient: pollen sublingual immunotherapy (SLIT) and high-dose hypoallergenic
      (allergoid) or unmodified depot pollen and mite preparations for subcutaneous
      immunotherapy (SCIT). To identify patients' compliance, "completed treatment
      years" were determined. A completed treatment year was defined by the required
      number of prescribed allergen preparations according to the recommended dosage
      scheme given in the respective SmPCs. RESULTS: Prescription data of 85,241
      patients receiving pollen or mite SCIT and 706 patients receiving pollen SLIT
      were included in this analysis. Patients' compliance for at least 3 treatment
      years with high-dose hypoallergenic pollen SCIT was higher when administered
      perennially (60%) compared to preseasonally (27%). Prescriptions for at least 3
      years were received from 42% of patients with pollen SCIT and from 45% of
      patients with mite SCIT. Compliance with SLIT was lowest with only 16% of
      patients receiving prescriptions for at least 3 treatment years. Children and
      adolescents were more compliant than adults, independent of whether they received
      SLIT or SCIT. CONCLUSION: In general, patients' compliance with SCIT using high
      dose hypoallergenic or unmodified depot preparations was higher than with pollen
      SLIT. Perennial application of SCIT seems to increase compliance in comparison to
      the preseasonal application. Children and adolescents were most compliant,
      independent of the preparation applied.

PMID- 25368518
TI  - Increased gene delivery efficiency and specificity of a lipid-based nanosystem
      incorporating a glycolipid.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of death related to
      cancer diseases worldwide. The current treatment options have many limitations
      and reduced success rates. In this regard, advances in gene therapy have shown
      promising results in novel therapeutic strategies. However, the success of gene
      therapy depends on the efficient and specific delivery of genetic material into
      target cells. In this regard, the main goal of this work was to develop a new
      lipid-based nanosystem formulation containing the lipid lactosyl-PE for specific
      and efficient gene delivery into HCC cells. The obtained results showed that
      incorporation of 15% of lactosyl-PE into liposomes induces a strong potentiation
      of lipoplex biological activity in HepG2 cells, not only in terms of transgene
      expression levels but also in terms of percentage of transfected cells. In the
      presence of galactose, which competes with lactosyl-PE for the binding to the
      asialoglycoprotein receptor (ASGP-R), a significant reduction in biological
      activity was observed, showing that the potentiation of transfection induced by
      the presence of lactosyl-PE could be due to its specific interaction with ASGP-R,
      which is overexpressed in HCC. In addition, it was found that the incorporation
      of lactosyl-PE in the nanosystems promotes an increase in their cell binding and
      uptake. Regarding the physicochemical properties of lipoplexes, the presence of
      lactosyl-PE resulted in a significant increase in DNA protection and in a
      substantial decrease in their mean diameter and zeta potential, conferring them
      suitable characteristics for in vivo application. Overall, the results obtained
      in this study suggest that the potentiation of the biological activity induced by
      the presence of lactosyl-PE is due to its specific binding to the ASGP-R, showing
      that this novel formulation could constitute a new gene delivery nanosystem for
      application in therapeutic strategies in HCC. 

PMID- 25368519
TI  - Optimal management of infrainguinal arterial occlusive disease.
AB  - Peripheral arterial occlusive disease is becoming a major health problem in
      Western societies as the population continues to age. In addition to risk of limb
      loss, the complexity of the disease is magnified by its intimate association with
      medical comorbidity, especially cardiovascular and cerebrovascular disease. Risk
      factor modification and antiplatelet therapy are essential to improve long-term
      survival. Surgical intervention is indicated for intermittent claudication when a
      patient's quality of life remains unacceptable after a trial of conservative
      therapy. Open reconstruction and endovascular revascularization are cornerstone
      for limb salvage in patients with critical limb ischemia. Recent advances in
      catheter-based technology have made endovascular intervention the preferred
      treatment approach for infrainguinal disease in many cases. Nevertheless, lower
      extremity bypass remains an important treatment strategy, especially for
      reasonable risk patients with a suitable bypass conduit. In this review, we
      present a summary of current knowledge about peripheral arterial disease followed
      by a review of current, evidence-based medical and surgical therapy for
      infrainguinal arterial occlusive disease. 

PMID- 25368520
TI  - RAD51B Activity and Cell Cycle Regulation in Response to DNA Damage in Breast
      Cancer Cell Lines.
AB  - Common genetic variants mapping to two distinct regions of RAD51B, a paralog of
      RAD51, have been associated with breast cancer risk in genome-wide association
      studies (GWAS). RAD51B is a plausible candidate gene because of its established
      role in the homologous recombination (HR) process. How germline genetic variation
      in RAD51B confers susceptibility to breast cancer is not well understood. Here,
      we investigate the molecular function of RAD51B in breast cancer cell lines by
      knocking down RAD51B expression by small interfering RNA and treating cells with
      DNA-damaging agents, namely cisplatin, hydroxyurea, or methyl-methanesulfonate.
      Our results show that RAD51B-depleted breast cancer cells have increased
      sensitivity to DNA damage, reduced efficiency of HR, and altered cell cycle
      checkpoint responses. The influence of RAD51B on the cell cycle checkpoint is
      independent of its role in HR and further studies are required to determine
      whether these functions can explain the RAD51B breast cancer susceptibility
      alleles. 

PMID- 25368522
TI  - Downregulated Ku70 and ATM associated to poor prognosis in colorectal cancer
      among Chinese patients.
AB  - BACKGROUND: Double-strand DNA breaks (DSBs) are a key factor in carcinogenesis.
      The necessary repair of DSBs is pivotal in maintaining normal cell division. To
      address the relationship between altered expression of DSB repair of proteins
      Ku70 and ataxia-telangiectasia mutated (ATM) in colorectal cancer (CRC), we
      examined the expression levels and patterns of Ku70 and ATM in CRC samples.
      METHODS: Expression and coexpression of Ku70 and ATM were investigated by using
      real-time quantitative polymerase chain reaction assays and confirmed further
      with fluorescent immunohistochemistry in CRC and pericancerous samples from 112
      Chinese patients. RESULTS: Downexpression patterns for both Ku70 and ATM were
      found in the CRC samples and were significantly associated with advanced tumor
      node metastasis stage and decreased 5-year overall survival rate. CONCLUSION:
      Downregulated Ku70 and ATM were associated with poor disease-free survival. Loss
      of Ku70 and ATM expression might act as a biomarker to predict poor prognosis in
      patients with CRC.

PMID- 25368521
TI  - Hereditary breast cancer: clinical, pathological and molecular characteristics.
AB  - Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with
      a strong history of breast cancer, though hereditary factors are expected to be
      involved in the remaining families with no recognized mutation. Molecular
      characterization is expected to provide new insight into the tumor biology to
      guide the search of new high-risk alleles and provide better classification of
      the growing number of BRCA1/2 variants of unknown significance (VUS). In this
      review, we provide an overview of hereditary breast cancer, its genetic
      background, and clinical implications, before focusing on the pathologically and
      molecular features associated with the disease. Recent transcriptome and genome
      profiling studies of tumor series from BRCA1/2 mutation carriers as well as
      familial non-BRCA1/2 will be discussed. Special attention is paid to its
      association with molecular breast cancer subtypes as well as the latest advances
      in predicting BRCA1/2 involvement (BRCAness) using molecular signatures, for
      improved diagnostics and selection of patients sensitive to targeted
      therapeutics. 

PMID- 25368523
TI  - The transcription factor KLF4 as an independent predictive marker for pathologic
      complete remission in breast cancer neoadjuvant chemotherapy: a case-control
      study.
AB  - BACKGROUND: To identify whether a stem cell biomarker, KLF4, may predict the
      pathologic tumor response to neoadjuvant chemotherapy for patients with locally
      advanced breast cancer. METHODS: Twelve locally advanced breast cancer patients
      who achieved pathologic complete remission (pCR) after neoadjuvant chemotherapy
      were identified and for each, three non-pCR breast cancer patients - matched for
      age, clinical tumor-node-metastasis stage, and neoadjuvant chemotherapy cycles -
      were selected. The relationship between KLF4 expression in the core needle
      biopsied cancer tissue and patient pCR rate was assessed using univariate and
      multivariate analysis. RESULTS: Receiver operating characteristic curve analysis
      showed that the patients with a histoscore of KLF4 expression >0.18 had a lower
      pCR rate. Multivariable analysis showed that higher KLF4 expression (odds ratio
      0.013; 95% confidence interval 0.013-0.444; P=0.004) was independently correlated
      with a lower pCR rate after neoadjuvant chemotherapy. CONCLUSION: KLF4
      overexpression was associated with lower pCR in locally advanced breast cancer
      patients undergoing neoadjuvant chemotherapy. This study suggests that KLF4 may
      serve as a predictor for pCR in patients with breast cancer after neoadjuvant
      chemotherapy.

PMID- 25368524
TI  - Profile of belinostat for the treatment of relapsed or refractory peripheral T
      cell lymphoma.
AB  - The peripheral T-cell lymphomas are a rare and heterogeneous group of mature T
      cell lymphomas with limited available therapies. The outcome of frontline
      chemotherapy regimens has been disappointing, with a long-term survival of only
      20%-30%. There is an urgent need to optimize induction therapy by incorporating
      novel agents that target the dysregulated pathways. Histone deacetylase
      inhibitors that induce acetylation of histones and enhance apoptosis have shown
      promising activity. In this article, we summarize the role of histone deacetylase
      inhibitors and specifically discuss pharmacokinetics, efficacy, and toxicity of
      the recently US Food and Drug Administration-approved agent belinostat for its
      use in patients with relapsed/refractory peripheral T-cell lymphoma. 

PMID- 25368526
TI  - An economic model to compare linezolid and vancomycin for the treatment of
      confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in
      Germany.
AB  - BACKGROUND: Across Europe, methicillin-resistant Staphylococcus aureus (MRSA) is
      considered to be the primary cause of nosocomial pneumonia (NP). In Germany
      alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may
      have a significant impact on health care resource use and associated economic
      costs. The objective of this study was to investigate the economic impact of
      linezolid compared with that of vancomycin in the treatment of hospitalized
      patients with MRSA-confirmed NP in the German health care system. METHODS: A 4
      week decision tree model incorporated published data and expert opinion on
      clinical parameters, resource use, and costs (2012 euros) was constructed. The
      base case first-line treatment duration for patients with MRSA-confirmed NP was
      10 days. Treatment success (survival), failure due to lack of efficacy, serious
      adverse events, and mortality were possible outcomes that could impact costs.
      Alternate scenarios were analyzed, such as varying treatment duration (7 or 14
      days) or treatment switch due to a serious adverse event/treatment failure (at
      day 5 or 10). RESULTS: The model calculated total base case inpatient costs of
      ?15,116 for linezolid and ?15,239 for vancomycin. The incremental cost
      effectiveness ratio favored linezolid (versus vancomycin), with marginally lower
      costs (by ?123) and greater efficacy (+2.7% absolute difference in the proportion
      of patients successfully treated for MRSA NP). Approximately 85%-87% of the total
      treatment costs were attributed to hospital stay (primarily in the intensive care
      unit). Sensitivity analysis yielded similar results. CONCLUSION: The model
      results show that linezolid is a cost-effective alternative to vancomycin for
      MRSA-confirmed NP, largely attributable to the higher clinical response rate of
      patients treated with linezolid.

PMID- 25368525
TI  - Diagnosis and management of food allergies: new and emerging options: a
      systematic review.
AB  - It is reported that 6% of children and 3% of adults have food allergies, with
      studies suggesting increased prevalence worldwide over the last few decades.
      Despite this, our diagnostic capabilities and techniques for managing patients
      with food allergies remain limited. We have conducted a systematic review of
      literature published within the last 5 years on the diagnosis and management of
      food allergies. While the gold standard for diagnosis remains the double-blind,
      placebo-controlled food challenge, this assessment is resource intensive and
      impractical in most clinical situations. In an effort to reduce the need for the
      double-blind, placebo-controlled food challenge, several risk-stratifying tests
      are employed, namely skin prick testing, measurement of serum-specific
      immunoglobulin E levels, component testing, and open food challenges. Management
      of food allergies typically involves allergen avoidance and carrying an
      epinephrine autoinjector. Clinical research trials of oral immunotherapy for some
      foods, including peanut, milk, egg, and peach, are under way. While oral
      immunotherapy is promising, its readiness for clinical application is
      controversial. In this review, we assess the latest studies published on the
      above diagnostic and management modalities, as well as novel strategies in the
      diagnosis and management of food allergy. 

PMID- 25368527
TI  - Prevalence of cardiometabolic risk factors and metabolic syndrome in obese
      Kuwaiti adolescents.
AB  - BACKGROUND: Childhood and adolescent obesity is associated with insulin
      resistance, abnormal glucose metabolism, hypertension, dyslipidemia,
      inflammation, liver disease, and compromised vascular function. The purpose of
      this pilot study was to determine the prevalence of cardiometabolic risk factor
      abnormalities and metabolic syndrome (MetS) in a sample of obese Kuwaiti
      adolescents, as prevalence data might be helpful in improving engagement with
      obesity treatment in future. METHODS: Eighty obese Kuwaiti adolescents (40 males)
      with a mean (standard deviation) age of 12.3 years (1.1 years) participated in
      the present study. All participants had a detailed clinical examination and
      anthropometry, blood pressure taken, and assessment of fasting levels of C
      reactive protein, intracellular adhesion molecule, interleukin-6, fasting blood
      glucose, insulin, liver function tests (alanine aminotransferase, aspartate
      aminotransferase, gamma glutamyltransferase), lipid profile (cholesterol, low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol,
      triglycerides), insulin resistance by homeostasis model assessment, and
      adiponectin. MetS was assessed using two recognized criteria modified for use in
      younger individuals. RESULTS: The cardiometabolic risk factors with highest
      prevalence of abnormal values included aspartate aminotransferase (88.7% of the
      sample) and insulin resistance by homeostasis model assessment (67.5%),
      intracellular adhesion molecule (66.5%), fasting insulin (43.5%), C-reactive
      protein (42.5%), low-density lipoprotein cholesterol (35.0%), total cholesterol
      (33.5%), and systolic blood pressure (30.0%). Of all participants, 96.3% (77/80)
      had at least one impaired cardiometabolic risk factor as well as obesity.
      Prevalence of MetS was 21.3% according to the International Diabetes Federation
      definition and 30% using the Third Adult Treatment Panel definition. CONCLUSION:
      The present study suggests that obese Kuwaiti adolescents have multiple
      cardiometabolic risk factor abnormalities. Future studies are needed to test the
      benefits of intervention in this high-risk group. They also suggest that
      prevention of obesity in children and adults should be a major public health goal
      in Kuwait.

PMID- 25368528
TI  - Relationship between oxidized low-density lipoprotein antibodies and obesity in
      different glycemic situations.
AB  - BACKGROUND: Autoantibodies to oxidized low-density lipoprotein (oxLDL) are a
      heterogeneous group of antibodies that are controversially discussed to be either
      pathogenic or protective. Biochemical and anthropometric measurements correlated
      with increased levels of these antibodies are also controversial, especially in
      conditions of impaired glucose tolerance and type 2 diabetes mellitus. The
      present study was conducted to evaluate levels of oxLDL antibodies and their
      correlation with obesity in different glycemic situations. METHODS: Two hundred
      and seventy-four adult males were classified into three subgroups: group 1
      (n=125), comprising a control group of nondiabetic subjects; group 2 (n=77),
      comprising subjects with impaired glucose tolerance; and group 3 (n=72),
      comprising patients with type 2 diabetes mellitus. Body mass index was
      calculated, and measurement of oxLDL and oxLDL antibodies was performed. RESULTS:
      Higher mean concentrations of oxLDL were found in the type 2 diabetes mellitus
      and impaired glucose tolerance groups (143.5+/-21.9 U/L and 108.7+/-23.7 U/L,
      respectively). The mean value for the control group was 73.5+/-27.5 U/L
      (P<0.001). Higher mean concentrations of anti-oxLDL antibodies were observed in
      the type 2 diabetes mellitus and impaired glucose tolerance groups (55.7+/-17.8
      U/L and 40.4+/-17.6 U/L, respectively). The mean value for the control group was
      20.4+/-10 U/L (P<0.001). Levels of anti-oxLDL antibodies were found to be
      positively and significantly correlated with body mass index in the control group
      (r=0.46), impaired glucose tolerance (r=0.51), type 2 diabetes mellitus group
      (r=0.46), and in the whole study population (r=0.44; P<0.001). CONCLUSION: Anti
      oxLDL antibody levels were increased in subjects with type 2 diabetes mellitus
      and impaired glucose tolerance and were positively correlated with obesity and
      body mass index.

PMID- 25368529
TI  - Preliminary open-label clinical evaluation of the soothing and
      reepithelialization properties of a novel topical formulation for rosacea.
AB  - BACKGROUND: Rosacea is a common, incurable skin barrier disorder characterized by
      relapses and remissions. PURPOSE: To evaluate the efficacy of Farmaka Rosacea
      Cream (FRC), a novel topical formulation for rosacea. METHODS: This single
      center, open-label pilot study comprised a single-dose substudy in 20 healthy
      subjects and a long-term, repeat-dose substudy in 22 subjects with rosacea. The 2
      hour, controlled, single-dose substudy assessed the soothing and
      reepithelialization properties of FRC after stripping-induced erythema based on
      the erythema index, transepidermal water loss, skin hydration, and clinical
      assessments of erythema. In the long-term substudy, subjects applied FRC twice
      daily for 8 weeks. Clinical assessments included vascular and pigmentary
      homogeneity and erythema and hemoglobin indices. Subjects completed
      questionnaires to assess FRC efficacy and cosmetic acceptability. RESULTS:
      Greater reductions were seen in FRC-treated areas compared with untreated areas
      for the erythema index (-16% versus -8%; P<0.001) and mean transepidermal water
      loss (-35.8% versus -10.1%; P<0.001) 30 minutes after stripping. Significant
      improvements over untreated areas were maintained 2 hours after stripping. Skin
      hydration and clinical erythema assessments also indicated that FRC soothed
      rosacea symptoms and promoted skin reepithelialization. Erythema and hemoglobin
      indices were significantly reduced from baseline after 4 and 8 weeks of
      treatment. Clinically assessed parameters were significantly improved following
      FRC application. Subjects assessed FRC positively. CONCLUSION: Improvement of
      rosacea symptoms was noted with FRC application. The main film-forming
      ingredients of FRC (trehalose, cholesterol, ceramide, and fatty acids), combined
      with other soothing and calming ingredients and ultraviolet filters, could
      explain its efficacy.

PMID- 25368530
TI  - PDLA a potential new potent topical analgesic: a case report.
AB  - Polymer D-lactic acid (PDLA) is a hydrogel that has been shown to sequester L
      lactate (lactate). This reaction is rapid, spontaneous, and non-enzymatic.
      Lactate has been shown to have many functions within the nervous system including
      its use as a secondary fuel to sustain neural activity and as a neuromodulator.
      In the central nervous system, lactate is produced in glial cells and shuttled to
      neurons to be used mostly as a fuel. Lactate dehydrogenase (LDH)1 is the
      predominant LDH isoform within neurons and unlike LDH5, it preferentially
      converts lactate to pyruvate which can be used to produce adenosine triphosphate
      (ATP). Considering that lactate is intimately involved in the sustenance of
      neural activity, PDLA was applied to an open wound and its effects were examined.
      The results showed that the application of PDLA induced topical analgesia. This
      may be the first report to demonstrate that sequestering lactate, a source of
      energy required to sustain the firing of action potentials in neurons, may
      produce analgesia. 

PMID- 25368532
TI  - Utilizing national patient-register data to control for comorbidity in prognostic
      studies.
AB  - OBJECTIVE: To construct an updated comorbidity index (Patient Register Index
      [PRI]) using national data collections from Norway and compare its predictive
      ability of 1-year mortality with the Charlson Comorbidity Index (CCI). MATERIALS
      AND METHODS: Data regarding over 1.11 million patients registered in the
      Norwegian Patient Register in 2010 and 2011 were used to construct the PRI. The
      PRI was evaluated by comparing its model fit and discrimination with the CCI.
      RESULTS: Compared with the CCI, the PRI weights decreased for six, increased for
      four, and were unchanged for seven diseases. When the PRI was added to the model
      including age and sex, the age effects were reduced by up to 38% for patients
      older than 50 years. All measures of model fit improved for the PRI model.
      CONCLUSION: Adjustment for comorbidity is especially important for patients 50
      years of age or older, and its effect on 1-year mortality is almost comparable to
      the age effect. The PRI is based on more recent data than the CCI, and is more
      representative of the general population due to its construction.

PMID- 25368531
TI  - Polyarticular juvenile idiopathic arthritis - epidemiology and management
      approaches.
AB  - Juvenile idiopathic arthritis (JIA) is a group of disorders characterized by
      arthritis persisting for at least 6 weeks with onset before the age of 16 years.
      Within this cluster of conditions, the polyarticular form (involving more than
      four joints within the first 6 months) is further divided based on the presence
      of rheumatoid factor. Children with polyarticular JIA pose unique diagnostic and
      therapeutic challenges compared to children with involvement of fewer joints.
      Polyarticular JIA patients tend to have a more refractory course and therefore
      are at increased risk for joint damage, resulting in poorer functional outcomes
      and decreased quality of life. Although the ability to treat this disorder
      continues to improve, especially with the advent of biologic agents, there is
      still much about the epidemiology and pathogenesis of polyarticular JIA that is
      unknown. The epidemiology of polyarticular JIA varies worldwide with a vast
      difference in reported cases between different global regions as well as within
      individual countries. Several genetic risk loci have been identified conferring
      increased susceptibility to JIA, many within the human leukocyte antigen region.
      Beyond the genome, environmental factors also seem to contribute to the etiology
      of polyarticular JIA. This review article will focus on the epidemiology and
      current treatments of polyarticular JIA and briefly discuss genetic and
      environmental influences on the pathogenesis of JIA as well as new and emerging
      therapies. 

PMID- 25368533
TI  - Predictors of poor glycemic control in type 2 diabetic patients attending public
      hospitals in Dar es Salaam.
AB  - BACKGROUND: Tanzania has recently experienced a significant rise in the burden of
      diabetes, and it is estimated that more than 400,000 people are living with
      diabetes. A major concern in the management of diabetes is the occurrence of
      diabetic complications that occur as a result of poor glycemic control.
      Identification of the factors associated with poor glycemic control is important
      in order to institute appropriate interventions for the purpose of improving
      glycemic control and prevention of chronic complications. AIM: The aim of this
      study was to determine the level of glycemic control and explore the factors
      associated with poor glycemic control among patients with type 2 diabetes
      mellitus (T2DM). METHODOLOGY: A cross-sectional study was carried out at the
      diabetic clinics for T2DM patients at the national and municipal hospitals in Dar
      es Salaam. A total of 469 patients were enrolled over a period of 8 weeks from
      March 2013 to May 2013. Patients' information such as sociodemographic
      characteristics, self-care management behaviors, and medication adherence were
      obtained through interviews. Blood pressure, weight, and height were measured
      during the day of the interview. All available last readings for fasting blood
      glucose (FBG) measurements, lipid profile, and other clinical characteristics
      were obtained from patients' records. RESULTS: The mean age of patients was 54.93
      years. The majority (63.5%) of patients were females and only eight patients had
      records of lipid profile measurements. Out of 469 patients, 69.7% had FBG of
      >=7.2 mmol/L, indicating poor glycemic control. Females aged between 40 years and
      59 years had significantly higher poor glycemic control (76.1%) as compared with
      their male counterparts. Thirty-eight percent of patients had poor medication
      adherence, which was associated with poor glycemic control. The proportion of
      poor glycemic control increased with age. A significantly high proportion of poor
      glycemic control was observed in patients who had had the disease for more than
      20 years since diagnosis. Factors associated with poor glycemic control included
      lack of health insurance, using more than one oral hypoglycemic agent, normal
      body mass index, obesity, and nonadherence to diabetic medications. CONCLUSION:
      Patients in this study had generally poor glycemic control. From these findings
      it is recommended that diabetic patients should be routinely screened for lipid
      profile to determine levels of cholesterol, triglycerides, and low-density
      lipoproteins, which are risk factors for cardiovascular events. An education
      program should be developed to educate patients on the importance of medication
      adherence and weight management for better glycemic control.

PMID- 25368535
TI  - Migraine: is it related to hormonal disturbances or stress?
AB  - BACKGROUND: Common neurological syndrome (migraine without aura) is more common
      among women than men. Migraine is among the top 20 causes of disability.
      Menstruation is known to be a powerful trigger for migraine, and so is stress,
      but the presentation of headache is similar in both. Also, women are more
      vulnerable to stress as well as migraine, and this makes a complex relationship
      of menstruation, stress, and migraine. OBJECTIVE: This study was done to
      understand the association of hormonal fluctuation in menstruation and stress
      with common migraine. MATERIALS AND METHODS: A cross-sectional comparative study
      was conducted in 40 young adult females, of whom 20 participants were cases of
      migraine without aura (18-35 years old), and the remaining 20 participants were
      age-matched controls. The study was done in Maulana Azad Medical College, New
      Delhi. Study participants were selected on the basis of International Headache
      Society (ICHD-IIA1.1) (2004) classification. Study participants with neurological
      disorders, chronic diseases, and disease suggestive of any hormonal disturbances
      were excluded. Clinically diagnosed migraine cases were asked to maintain a
      headache diary and to fill in the Depression Anxiety Stress Scales questionnaire.
      Biochemical assessment of hormonal status for thyroid-stimulating hormone,
      triiodothyronine, thyroxine, estrogen, follicle-stimulating hormone, luteinizing
      hormone, and prolactin was also done on the second day of their menstrual cycle.
      We used the Mann-Whitney U test to compare hormonal levels and the chi (2) test
      to compare anxiety- or depression-related stress among the migraine and
      nonmigraine groups. RESULTS: Significantly higher values of prolactin were
      observed in cases (mean +/- standard deviation, 152.7 mIU/L+/-30.5) compared to
      controls (76.1 mIU/L+/-8.7), with a P-value <0.001. There was no statistically
      significant difference observed in levels of thyroid-stimulating hormone
      (P=0.081), estrogen (P=0.086), luteinizing hormone (P=0.091), or follicle
      stimulating hormone (P=0.478). Also, anxiety with stress or depression with
      stress was significantly higher among the migraine group than the controls
      (P=0.002). Odds of any stress in migraine were higher in the migraine group than
      in the nonmigraine group (odds ratio 12, 95% confidence interval 2.7-53.33).
      CONCLUSION: Migraine, particularly without aura, in women is mainly associated
      with stress-related anxiety or depression, and are more susceptible to stress in
      the premenstrual period.

PMID- 25368536
TI  - Visualization analysis of research hotspots based on CiteSpace II: taking medical
      devices as an example.
AB  - Biomedical engineering has been one of the hottest fields in biology and
      engineering. As an important branch, the medical device has achieved significant
      progress in the past decades. As a useful method in evaluative bibliometrics,
      mapping knowledge has been used to explore the trend of one field. In the present
      study, we retrieve literatures about the medical device from the Web of ScienceTM
      (2004-2013), and acquire 26,793 related records, then analyze time range, region
      distribution, and main research directions of the literatures, and try to use
      keywords combined with mapping knowledge to explore the main trends of the
      medical device, and then aim to provide more information for medical device
      research. Through the study, we discover: 1) the publications regarding medical
      devices show an upward trend over the past decade in general; 2) the percentage
      of publications in the USA (38.49%) is the highest all over the world; 3)
      engineering (20.64%) is the hottest research direction, and takes up about one
      fifth of the total publications; 4) the Journal of the American Medical
      Association and The New England Journal of Medicine are among the two journals
      that are the most highly cited, followed by Science and The Lancet; and 5)
      keywords of the medical device include in vitro, quality-of-life, outcomes,
      management, mortality, depression, and so on. With the help of mapping knowledge,
      we dig out some hot topics of medical devices and provide more information
      through trend analysis, and we discover that our findings are related to previous
      research and further research can enlarge the number of records and optimize the
      algorithm. We provide a systematic approach for researchers to keep abreast of
      the development and state of the research of medical devices. 

PMID- 25368534
TI  - Current perspectives in HIV post-exposure prophylaxis.
AB  - The incidence of human immunodeficiency virus (HIV) infection continues to rise
      among core groups and efforts to reduce the numbers of new infections are being
      redoubled. Post-exposure prophylaxis (PEP) is the use of short-term
      antiretroviral therapy (ART) to reduce the risk of acquisition of HIV infection
      following exposure. Current guidelines recommend a 28-day course of ART within 36
      72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV
      there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the
      vast majority of which is for sexual exposure (PEPSE), has a significant role to
      play in HIV prevention efforts. Awareness of PEP and its availability for both
      clinicians and those who are eligible to receive it are crucial to ensure that
      PEP is used to its full potential in any HIV prevention strategy. In this review,
      we provide current evidence for the use of PEPSE, assessment of the risk of HIV
      transmission, indications for PEP, drug regimens, and management of patients
      started on PEP. We summarize national and international guidelines for the use of
      PEPSE. We explore the place of PEP within the wider strategy of reducing HIV
      incidence rates in the era of treatment as prevention and pre-exposure
      prophylaxis. We also consider the implications of recent data from interventional
      and observational studies demonstrating significant reductions in the risk of HIV
      transmission within a serodiscordant relationship if the HIV-positive partner is
      taking effective ART upon PEP guidelines. 

PMID- 25368537
TI  - Performance of health product risk management and surveillance conducted by
      health personnel at sub-district health promotion hospitals in the northeast
      region of Thailand.
AB  - BACKGROUND: Health personnel at sub-district health promotion hospitals (SD-HPHs)
      are assigned to take responsibility for 15 activities related to health product
      risk management and surveillance (HP-RM&S). This cross-sectional survey aimed to
      identify factors that determined their job performance and to record their
      expressed needs to support HP-RM&S operation. In this study, job performance was
      defined as completion of all 15 activities. METHODS: Self-administered postal
      questionnaires were used to collect data from 380 randomly selected health
      personnel who were in charge of HP-RM&S at SD-HPHs in the northeast of Thailand.
      RESULTS: Thirty-six point one percent (n=137) of the respondents were able to
      perform all 15 of the HP-RM&S activities assigned to SD-HPHs. A logistic
      regression model identified three factors that statistically significantly
      determined the completion of all 15 HP-RM&S activities. These were: receiving a
      high or very high level of support from the community (adjusted odds ratio [OR]:
      2.5; 95% confidence interval [CI]: 1.5, 4.1), the responsible persons for HP-RM&S
      did not hold an administrative position (adjusted OR: 1.7; 95% CI: 1.1, 2.7), and
      having at least one training session related to HP-RM&S per year (adjusted OR:
      1.7; 95% CI 1.1, 2.6). There were 1,536 expressed needs which can be classified
      into four major categories, ie, training needs (41.6%, n=639), resource support
      (28.3%, n=435), mechanisms that facilitate HP-RM&S operation (24.1%, n=370) and
      adjusting of the scope of HP-RM&S (6.0%, n=92). The topics most frequently
      referred to in training needs were drug law, food law, and cosmetics law.
      CONCLUSION: A strategy for improvement of the job performance in HP-RM&S of
      health personnel in SD-HPHs should target identifying schemes to encourage the
      community to proactively participate in HP-RM&S. The district health office as
      the organization directly controlling and supervising SD-HPHs should also
      regularly update knowledge base and skills necessary for HP-RM&S operation
      through training of the responsible health personnel.

PMID- 25368538
TI  - Effects of fibrosis morphology on reentrant ventricular tachycardia inducibility
      and simulation fidelity in patient-derived models.
AB  - Myocardial fibrosis detected via delayed-enhanced magnetic resonance imaging
      (MRI) has been shown to be a strong indicator for ventricular tachycardia (VT)
      inducibility. However, little is known regarding how inducibility is affected by
      the details of the fibrosis extent, morphology, and border zone configuration.
      The objective of this article is to systematically study the arrhythmogenic
      effects of fibrosis geometry and extent, specifically on VT inducibility and
      maintenance. We present a set of methods for constructing patient-specific
      computational models of human ventricles using in vivo MRI data for patients
      suffering from hypertension, hypercholesterolemia, and chronic myocardial
      infarction. Additional synthesized models with morphologically varied extents of
      fibrosis and gray zone (GZ) distribution were derived to study the alterations in
      the arrhythmia induction and reentry patterns. Detailed electrophysiological
      simulations demonstrated that (1) VT morphology was highly dependent on the
      extent of fibrosis, which acts as a structural substrate, (2) reentry tended to
      be anchored to the fibrosis edges and showed transmural conduction of activations
      through narrow channels formed within fibrosis, and (3) increasing the extent of
      GZ within fibrosis tended to destabilize the structural reentry sites and
      aggravate the VT as compared to fibrotic regions of the same size and shape but
      with lower or no GZ. The approach and findings represent a significant step
      toward patient-specific cardiac modeling as a reliable tool for VT prediction and
      management of the patient. Sensitivities to approximation nuances in the modeling
      of structural pathology by image-based reconstruction techniques are also
      implicated. 

PMID- 25368539
TI  - Diagnosis and management of valvular aortic stenosis.
AB  - Valvular aortic stenosis (AS) is a progressive disease that affects 2% of the
      population aged 65 years or older. The major cause of valvular AS in adults is
      calcification and fibrosis of a previously normal tricuspid valve or a congenital
      bicuspid valve, with rheumatic AS being rare in the United States. Once
      established, the rate of progression of valvular AS is quite variable and
      impossible to predict for any particular patient. Symptoms of AS are generally
      insidious at onset, though development of any of the three cardinal symptoms of
      angina, syncope, or heart failure portends a poor prognosis. Management of
      symptomatic AS remains primarily surgical, though transcatheter aortic valve
      replacement (TAVR) is becoming an accepted alternative to surgical aortic valve
      replacement (SAVR) for patients at high or prohibitive operative risk. 

PMID- 25368540
TI  - The association of pre-existing left atrial fibrosis with clinical variables in
      patients referred for catheter ablation of atrial fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) recurrence after ablation is associated
      with left atrial (LA) fibrosis on late gadolinium enhanced (LGE) magnetic
      resonance imaging (MRI). We sought to determine pre-ablation, clinical
      characteristics that associate with the extent of LA fibrosis in patients
      undergoing catheter ablation for AF. METHODS AND RESULTS: Consecutive patients
      presenting for catheter ablation of AF were enrolled and underwent LGE-MRI prior
      to initial AF ablation. The extent of fibrosis as a percentage of total LA
      myocardium was calculated in all patients prior to ablation. The cohort was
      divided into quartiles based on the percentage of fibrosis. Of 60 patients
      enrolled in the cohort, 13 had <5% fibrosis (Group 1), 15 had 5-7% fibrosis
      (Group 2), 17 had 8-13% fibrosis (Group 3), and 15 had 14-36% fibrosis (Group 4).
      The extent of LA fibrosis was positively associated with time in continuous AF,
      and the presence of persistent or longstanding persistent AF. However, no
      statistically significant difference was observed in the presence of comorbid
      conditions, age, BMI, LA volume, or family history of AF among the four groups.
      After adjusting for diabetes and hypertension in a multivariable linear
      regression model, paroxysmal AF remained independently and negatively associated
      with the extent of fibrosis (-4.0 +/- 1.8, P = 0.034). CONCLUSION: The extent of
      LA fibrosis in patients undergoing AF ablation is associated with AF type and
      time in continuous AF. Our results suggest that the presence and duration of AF
      are primary determinants of increased atrial LGE.

PMID- 25368541
TI  - Prospective Randomized Trial on Postoperative Administration of Diet Containing
      Eicosapentaenoic Acid, Docosahexaenoic Acid, Gamma-linolenic Acid, and
      Antioxidants in Head and Neck Cancer Surgery Patients with Free-flap
      Reconstruction.
AB  - OBJECTIVES: The purpose of this prospective, randomized study was to evaluate the
      effects of a diet containing eicosapentaenoic acid (EPA), docosahexaenoic acid
      (DHA), gamma-linolenic acid (GLA), and antioxidants in head and neck cancer
      surgery patients with free-flap reconstruction. METHODS: In this randomized,
      prospective study, 62 patients with head and neck cancers were assigned to
      receive a general control diet (Ensure((r)) H; Abbott Japan, Tokyo, Japan) or the
      study diet (Oxepa((r)); Abbott Japan) containing EPA, DHA, GLA, and antioxidants
      (eg vitamins A, E, and C). The primary assessment item was the degree of
      postoperative inflammation, as assessed by measuring maximum body temperature and
      levels of C-reactive protein (CRP) and procalcitonin from the day of surgery to
      postoperative day 8. Secondary assessment items were lengths of stays in the
      intensive care unit (ICU) and hospital. RESULTS: The control diet group (n = 32)
      and study diet group (n = 30) showed no significant difference in energy
      administered through diet. No significant differences in the parameters of the
      primary assessment item were noted. Length of stay in the ICU was significantly
      shorter for the control diet group than for the study diet group (P = 0.011). No
      significant difference in duration of hospitalization was seen between groups.
      CONCLUSION: No usefulness of a diet containing EPA, DHA, GLA, and antioxidants
      was demonstrated.

PMID- 25368542
TI  - Factors influencing Saudi medical students and interns' choice of future
      specialty: a self-administered questionnaire.
AB  - BACKGROUND: This study explores the most influential factors affecting Saudi
      medical students and interns' choice of specialty at the University of Dammam,
      Kingdom of Saudi Arabia. METHODS: A self-administered questionnaire was
      distributed during the period from June 1 to June 14, 2013. Chi-square test and
      logistic regression were used to test the association between participants'
      choices and the motivational factors that led to their choice of specialty.
      RESULTS: One-hundred sixty-eight (44.7%) participants chose lifestyle as their
      most influential factor for the choice of their specialty. Significantly more
      medical interns considered lifestyle as an important factor compared to medical
      students (P=0.020). Internal medicine was the preferred specialty for 56
      participants (14.77%) followed by family medicine for 35 participants (9.2%).
      Thirty-four participants (8.97%) chose general surgery, and 27 participants
      (7.1%) chose both pediatrics and emergency medicine. Sex influences indicated
      that men preferred pediatrics and emergency medicine (P=0.033 and P=0.0006,
      respectively), while women preferred family medicine practice (P=0.034).
      CONCLUSION: Saudi medical students and interns at the University of Dammam were
      influenced mostly by lifestyle when they considered their future specialty.
      Internal medicine, family medicine, general surgery, pediatrics, and emergency
      medicine were the preferred specialties.

PMID- 25368543
TI  - Sinks as limited resources? A new indicator for evaluating anthropogenic material
      flows.
AB  - Besides recyclables, the use of materials inevitably yields non-recyclable
      materials such as emissions and wastes for disposal. These flows must be directed
      to sinks in a way that no adverse effects arise for humans and the environment.
      The objective of this paper is to present a new indicator for the assessment of
      substance flows to sinks on a regional scale. The indicator quantifies the
      environmentally acceptable mass share of a substance in actual waste and emission
      flows, ranging from 0% as worst case to 100% as best case. This paper consists of
      three parts: first, the indicator is defined. Second, a methodology to determine
      the indicator score is presented, including (i) substance flows analysis and (ii)
      a distant-to-target approach based on an adaptation of the Ecological Scarcity
      Method 2006. Third, the metric developed is applied in three case studies
      including copper (Cu) and lead (Pb) in the city of Vienna, and perfluorooctane
      sulfonate (PFOS) in Switzerland. The following results were obtained: in Vienna,
      99% of Cu flows to geogenic and anthropogenic sinks are acceptable when evaluated
      by the distant-to-target approach. However, the 0.7% of Cu entering urban soils
      and the 0.3% entering receiving waters are beyond the acceptable level. In the
      case of Pb, 92% of all flows into sinks prove to be acceptable, and 8% are
      disposed of in local landfills with limited capacity. For PFOS, 96% of all flows
      into sinks are acceptable. 4% cannot be evaluated due to a lack of normative
      criteria, despite posing a risk for human health and the environment. The
      examples demonstrate the need (i) for appropriate data of good quality to
      calculate the sink indicator and (ii) for standards, needed for the assessment of
      substance flows to urban soils and receiving waters. This study corroborates that
      the new indicator is well suited as a base for decisions regarding the control of
      hazardous substances in waste and environmental management.

PMID- 25368544
TI  - Effects of different flow patterns and end-inspiratory pause on oxygenation and
      ventilation in newborn piglets: an experimental study.
AB  - BACKGROUND: Historically, the elective ventilatory flow pattern for neonates has
      been decelerating flow (DF). Decelerating flow waveform has been suggested to
      improve gas exchange in the neonate when compared with square flow (SF) waveform
      by improving the ventilation perfusion. However, the superiority of DF compared
      with SF has not yet been demonstrated during ventilation in small infants. The
      aim of this study was to compare SF vs. DF, with or without end-inspiratory pause
      (EIP), in terms of oxygenation and ventilation in an experimental model of
      newborn piglets. METHODS: The lungs of 12 newborn Landrace/LargeWhite crossbred
      piglets were ventilated with SF, DF, SF-EIP and DF-EIP. Tidal volume (VT),
      inspiratory to expiratory ratio (I/E), respiratory rate (RR), and FiO2 were keep
      constant during the study. In order to assure an open lung during the study while
      preventing alveolar collapse, a positive end-expiratory pressure (PEEP) of 6
      cmH2O was applied after a single recruitment maneuver. Gas exchange, lung
      mechanics and hemodynamics were measured. RESULTS: The inspiratory flow waveform
      had no effect on arterial oxygenation pressure (PaO2) (276 vs. 278 mmHg, p =
      0.77), alveolar dead space to alveolar tidal volume (VDalv/VTalv) (0.21 vs. 0.19
      ml, p = 0.33), mean airway pressure (Pawm) (13.1 vs. 14.0 cmH2O, p = 0.69) and
      compliance (Crs) (3.5 vs. 3.5 ml cmH2O(-1), p = 0.73) when comparing SF and DF. A
      short EIP (10%) did not produce changes in the results. CONCLUSION: The present
      study showed that there are no differences between SF, DF, SF-EIP and DF-EIP in
      oxygenation, ventilation, lung mechanics, or hemodynamics in this experimental
      model of newborn piglets with healthy lungs.

PMID- 25368545
TI  - Young Children's Self-Generated Object Views and Object Recognition.

PMID- 25368546
TI  - Non-motor tasks improve adaptive brain-computer interface performance in users
      with severe motor impairment.
AB  - Individuals with severe motor impairment can use event-related desynchronization
      (ERD) based BCIs as assistive technology. Auto-calibrating and adaptive ERD-based
      BCIs that users control with motor imagery tasks ("SMR-AdBCI") have proven
      effective for healthy users. We aim to find an improved configuration of such an
      adaptive ERD-based BCI for individuals with severe motor impairment as a result
      of spinal cord injury (SCI) or stroke. We hypothesized that an adaptive ERD-based
      BCI, that automatically selects a user specific class-combination from motor
      related and non motor-related mental tasks during initial auto-calibration ("Auto
      AdBCI") could allow for higher control performance than a conventional SMR-AdBCI.
      To answer this question we performed offline analyses on two sessions (21 data
      sets total) of cue-guided, five-class electroencephalography (EEG) data recorded
      from individuals with SCI or stroke. On data from the twelve individuals in
      Session 1, we first identified three bipolar derivations for the SMR-AdBCI. In a
      similar way, we determined three bipolar derivations and four mental tasks for
      the Auto-AdBCI. We then simulated both, the SMR-AdBCI and the Auto-AdBCI
      configuration on the unseen data from the nine participants in Session 2 and
      compared the results. On the unseen data of Session 2 from individuals with SCI
      or stroke, we found that automatically selecting a user specific class
      combination from motor-related and non motor-related mental tasks during initial
      auto-calibration (Auto-AdBCI) significantly (p < 0.01) improved classification
      performance compared to an adaptive ERD-based BCI that only used motor imagery
      tasks (SMR-AdBCI; average accuracy of 75.7 vs. 66.3%). 

PMID- 25368547
TI  - Improving spatial localization in MEG inverse imaging by leveraging intersubject
      anatomical differences.
AB  - Modern neuroimaging techniques enable non-invasive observation of ongoing neural
      processing, with magnetoencephalography (MEG) in particular providing direct
      measurement of neural activity with millisecond time resolution. However,
      accurately mapping measured MEG sensor readings onto the underlying source neural
      structures remains an active area of research. This so-called "inverse problem"
      is ill posed, and poses a challenge for source estimation that is often cited as
      a drawback limiting MEG data interpretation. However, anatomically constrained
      MEG localization estimates may be more accurate than commonly believed. Here we
      hypothesize that, by combining anatomically constrained inverse estimates across
      subjects, the spatial uncertainty of MEG source localization can be mitigated.
      Specifically, we argue that differences in subject brain geometry yield
      differences in point-spread functions, resulting in improved spatial localization
      across subjects. To test this, we use standard methods to combine subject
      anatomical MRI scans with coregistration information to obtain an accurate
      forward (physical) solution, modeling the MEG sensor data resulting from brain
      activity originating from different cortical locations. Using a linear minimum
      norm inverse to localize this brain activity, we demonstrate that a substantial
      increase in the spatial accuracy of MEG source localization can result from
      combining data from subjects with differing brain geometry. This improvement may
      be enabled by an increase in the amount of available spatial information in MEG
      data as measurements from different subjects are combined. This approach becomes
      more important in the face of practical issues of coregistration errors and
      potential noise sources, where we observe even larger improvements in
      localization when combining data across subjects. Finally, we use a simple
      auditory N100(m) localization task to show how this effect can influence
      localization using a recorded neural dataset. 

PMID- 25368548
TI  - Sonification as a possible stroke rehabilitation strategy.
AB  - Despite cerebral stroke being one of the main causes of acquired impairments of
      motor skills worldwide, well-established therapies to improve motor functions are
      sparse. Recently, attempts have been made to improve gross motor rehabilitation
      by mapping patient movements to sound, termed sonification. Sonification provides
      additional sensory input, supplementing impaired proprioception. However, to date
      no established sonification-supported rehabilitation protocol strategy exists. In
      order to examine and validate the effectiveness of sonification in stroke
      rehabilitation, we developed a computer program, termed "SonicPointer":
      Participants' computer mouse movements were sonified in real-time with complex
      tones. Tone characteristics were derived from an invisible parameter mapping,
      overlaid on the computer screen. The parameters were: tone pitch and tone
      brightness. One parameter varied along the x, the other along the y axis. The
      order of parameter assignment to axes was balanced in two blocks between subjects
      so that each participant performed under both conditions. Subjects were naive to
      the overlaid parameter mappings and its change between blocks. In each trial a
      target tone was presented and subjects were instructed to indicate its origin
      with respect to the overlaid parameter mappings on the screen as quickly and
      accurately as possible with a mouse click. Twenty-six elderly healthy
      participants were tested. Required time and two-dimensional accuracy were
      recorded. Trial duration times and learning curves were derived. We hypothesized
      that subjects performed in one of the two parameter-to-axis-mappings better,
      indicating the most natural sonification. Generally, subjects' localizing
      performance was better on the pitch axis as compared to the brightness axis.
      Furthermore, the learning curves were steepest when pitch was mapped onto the
      vertical and brightness onto the horizontal axis. This seems to be the optimal
      constellation for this two-dimensional sonification. 

PMID- 25368549
TI  - DYRK1A-mediated phosphorylation of GluN2A at Ser(1048) regulates the surface
      expression and channel activity of GluN1/GluN2A receptors.
AB  - N-methyl-D-aspartate glutamate receptors (NMDARs) play a pivotal role in neural
      development and synaptic plasticity, as well as in neurological disease. Since
      NMDARs exert their function at the cell surface, their density in the plasma
      membrane is finely tuned by a plethora of molecules that regulate their
      production, trafficking, docking and internalization in response to external
      stimuli. In addition to transcriptional regulation, the density of NMDARs is also
      influenced by post-translational mechanisms like phosphorylation, a modification
      that also affects their biophysical properties. We previously described the
      increased surface expression of GluN1/GluN2A receptors in transgenic mice
      overexpressing the Dual specificity tyrosine-phosphorylation-regulated kinase 1A
      (DYRK1A), suggesting that DYRK1A regulates NMDARs. Here we have further
      investigated whether the density and activity of NMDARs were modulated by DYRK1A
      phosphorylation. Accordingly, we show that endogenous DYRK1A is recruited to
      GluN2A-containing NMDARs in the adult mouse brain, and we identify a DYRK1A
      phosphorylation site at Ser(1048) of GluN2A, within its intracellular C-terminal
      domain. Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at
      Ser(1048) hinders the internalization of GluN1/GluN2A, causing an increase of
      surface GluN1/GluN2A in heterologous systems, as well as in primary cortical
      neurons. Furthermore, GluN2A phosphorylation at Ser(1048) increases the current
      density and potentiates the gating of GluN1/GluN2A receptors. We conclude that
      DYRK1A is a direct regulator of NMDA receptors and we propose a novel mechanism
      for the control of NMDAR activity in neurons. 

PMID- 25368550
TI  - Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal
      oxidative stress.
AB  - Vasoinhibins are prolactin fragments present in the retina, where they have been
      shown to prevent the hypervasopermeability associated with diabetes. Enhanced
      bradykinin (BK) production contributes to the increased transport through the
      blood-retina barrier (BRB) in diabetes. Here, we studied if vasoinhibins regulate
      BRB permeability by targeting the vascular endothelium and retinal pigment
      epithelium (RPE) components of this barrier. Intravitreal injection of BK in male
      rats increased BRB permeability. Vasoinhibins prevented this effect, as did the
      B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal
      and brain capillary endothelial monolayer resistance that was blocked by
      vasoinhibins. Both vasoinhibins and the nitric oxide (NO) synthase inhibitor L
      NAME, but not the antioxidant N-acetyl cysteine (NAC), blocked the transient
      decrease in bovine umbilical vein endothelial cell (BUVEC) monolayer resistance
      induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins
      also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME.
      BK transiently decreased human RPE (ARPE-19) cell monolayer resistance, and this
      effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the
      blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox
      induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by
      vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton
      redistribution. Intravitreal injection of vasoinhibins reduced the levels of
      reactive oxygen species (ROS) in retinas of streptozotocin-induced diabetic rats,
      particularly in the RPE and capillary-containing layers. Thus, vasoinhibins
      reduce BRB permeability by targeting both its main inner and outer components
      through NO- and ROS-dependent pathways, offering potential treatment strategies
      against diabetic retinopathies. 

PMID- 25368551
TI  - Grafting and early expression of growth factors from adipose-derived stem cells
      transplanted into the cochlea, in a Guinea pig model of acoustic trauma.
AB  - Noise exposure causes damage of multiple cochlear cell types producing permanent
      hearing loss with important social consequences. In mammals, no regeneration of
      either damaged hair cells or auditory neurons has been observed and no successful
      treatment is available to achieve a functional recovery. Loads of evidence
      indicate adipose-derived stem cells (ASCs) as promising tools in diversified
      regenerative medicine applications, due to the high degree of plasticity and
      trophic features. This study was aimed at identifying the path of in vivo cell
      migration and expression of trophic growth factors, upon ASCs transplantation
      into the cochlea, following noise-induced injury. ASCs were isolated in primary
      culture from the adipose tissue of a guinea pig, transduced using a viral vector
      to express the green fluorescent protein, and implanted into the scala tympani of
      deafened animals. Auditory function was assessed 3 and 7 days after surgery. The
      expression of trophic growth factors was comparatively analyzed using real-time
      PCR in control and noise-injured cochlear tissues. Immunofluorescence was used to
      assess the in vivo localization and expression of trophic growth factors in ASCs
      and cochleae, 3 and 7 days following homologous implantation. ASC implantation
      did not modify auditory function. ASCs migrated from the perilymphatic to the
      endolymphatic compartment, during the analyzed time course. Upon noise exposure,
      the expression of chemokine ligands and receptors related to the PDGF, VEGF, and
      TGFbeta pathways, increased in the cochlear tissues, possibly guiding in vivo
      cell migration. Immunofluorescence confirmed the increased expression, which
      appeared to be further strengthened by ASCs' implantation. These results
      indicated that ASCs are able to migrate at the site of tissue damage and express
      trophic factors, upon intracochlear implantation, providing an original proof of
      principle, which could pave the way for further developments of ASC-based
      treatments of deafness. 

PMID- 25368552
TI  - Drug and xenobiotic biotransformation in the blood-brain barrier: a neglected
      issue.
AB  - Drug biotransformation is a crucial mechanism for facilitating the elimination of
      chemicals from the organism and for decreasing their pharmacological activity.
      Published evidence suggests that brain drug metabolism may play a role in the
      development of adverse drug reactions and in the clinical response to drugs and
      xenobiotics. The blood-brain barrier (BBB) has been regarded mainly as a physical
      barrier for drugs and xenobiotics, and little attention has been paid to the BBB
      as a drug-metabolizing barrier. The presence of drug-metabolizing enzymes in the
      BBB is likely to have functional implications because local metabolism may
      inactivate drugs or may modify the drug's ability to cross the BBB, thus
      modifying drug response and the risk of developing adverse drug reactions. In
      this perspective paper, we discuss the expression of relevant xenobiotic
      metabolizing enzymes in the brain and in the BBB, and we cover current advances
      and future directions on the potential role of these BBB drug-metabolizing
      enzymes as modifiers of drug response. 

PMID- 25368553
TI  - Commentary: Different immunological mechanisms govern protection from
      experimental stroke in young and older mice with recombinant TCR ligand therapy.

PMID- 25368557
TI  - A unifying computational framework for stability and flexibility of arousal.
AB  - Arousal and consciousness flexibly adjust to salient cues, but remain stable
      despite noise and disturbance. Diverse, highly interconnected neural networks
      govern the underlying transitions of behavioral state; these networks are robust
      but very complex. Frameworks from systems engineering provide powerful tools for
      understanding functional logic behind component complexity. From a general
      systems viewpoint, a minimum of three communicating control modules may enable
      flexibility and stability to coexist. Comparators would subtract current arousal
      from desired arousal, producing an error signal. Regulators would compute control
      signals from this error. Generators would convert control signals into arousal,
      which is fed back to comparators, to make the system noise-proof through self
      correction. Can specific neurons correspond to these control elements? To explore
      this, here we consider the brain-wide orexin/hypocretin network, which is
      experimentally established to be vital for flexible and stable arousal. We
      discuss whether orexin neurons may act as comparators, and their target neurons
      as regulators and generators. Experiments are proposed for testing such
      predictions, based on computational simulations showing that comparators,
      regulators, and generators have distinct temporal signatures of activity. If some
      regulators integrate orexin-communicated errors, robust arousal control may be
      achieved via integral feedback (a basic engineering strategy for tracking a set
      point despite noise). An integral feedback view also suggests functional roles
      for specific molecular aspects, such as differing life-spans of orexin peptides.
      The proposed framework offers a unifying logic for molecular, cellular, and
      network details of arousal systems, and provides insight into behavioral state
      transitions, complex behavior, and bases for disease. 

PMID- 25368555
TI  - Dissecting inhibitory brain circuits with genetically-targeted technologies.
AB  - The evolution of genetically targeted tools has begun to allow us to dissect
      anatomically and functionally heterogeneous interneurons, and to probe circuit
      function from synapses to behavior. Over the last decade, these tools have been
      used widely to visualize neurons in a cell type-specific manner, and engage them
      to activate and inactivate with exquisite precision. In this process, we have
      expanded our understanding of interneuron diversity, their functional
      connectivity, and how selective inhibitory circuits contribute to behavior. Here
      we discuss the relative assets of genetically encoded fluorescent proteins (FPs),
      viral tracing methods, optogenetics, chemical genetics, and biosensors in the
      study of inhibitory interneurons and their respective circuits.

PMID- 25368558
TI  - Impaired Cross-Talk between Mesolimbic Food Reward Processing and Metabolic
      Signaling Predicts Body Mass Index.
AB  - The anticipation of the pleasure derived from food intake drives the motivation
      to eat, and hence facilitate overconsumption of food, which ultimately results in
      obesity. Brain imaging studies provide evidence that mesolimbic brain regions
      underlie both general as well as food-related anticipatory reward processing. In
      light of this knowledge, the present study examined the neural responsiveness of
      the ventral striatum (VS) in participants with a broad BMI spectrum. The study
      differentiated between general (i.e., monetary) and food-related anticipatory
      reward processing. We recruited a sample of volunteers with greatly varying body
      weights, ranging from a low BMI (below 20 kg/m(2)) over a normal (20-25 kg/m(2))
      and overweight (25-30 kg/m(2)) BMI, to class I (30-35 kg/m(2)) and class II (35
      40 kg/m(2)) obesity. A total of 24 participants underwent functional magnetic
      resonance imaging while performing both a food and monetary incentive delay task,
      which allows to measure neural activation during the anticipation of rewards.
      After the presentation of a cue indicating the amount of food or money to be won,
      participants had to react correctly in order to earn "snack points" or "money
      coins," which could then be exchanged for real food or money, respectively, at
      the end of the experiment. During the anticipation of both types of rewards,
      participants displayed activity in the VS, a region that plays a pivotal role in
      the anticipation of rewards. Additionally, we observed that specifically
      anticipatory food reward processing predicted the individual BMI (current and
      maximum lifetime). This relation was found to be mediated by impaired hormonal
      satiety signaling, i.e., increased leptin levels and insulin resistance. These
      findings suggest that heightened food reward motivation contributes to obesity
      through impaired metabolic signaling. 

PMID- 25368559
TI  - Generalization of fear-potentiated startle in the presence of auditory cues: a
      parametric analysis.
AB  - Intense fear responses observed in trauma-, stressor-, and anxiety-related
      disorders can be elicited by a wide range of stimuli similar to those that were
      present during the traumatic event. The present study investigated the
      experimental utility of fear-potentiated startle paradigms to study this
      phenomenon, known as stimulus generalization, in healthy volunteers. Fear
      potentiated startle refers to a relative increase in the acoustic startle
      response to a previously neutral stimulus that has been paired with an aversive
      stimulus. Specifically, in Experiment 1 an auditory pure tone (500 Hz) was used
      as the conditioned stimulus (CS+) and was reinforced with an unconditioned
      stimulus (US), an airblast to the larynx. A distinct tone (4000 Hz) was used as
      the nonreinforced stimulus (CS-) and was never paired with an airblast. Twenty
      four hours later subjects underwent Re-training followed by a Generalization
      test, during which subjects were exposed to a range of generalization stimuli
      (GS) (250, 1000, 2000, 4000, 8000 Hz). In order to further examine the point at
      which fear no longer generalizes, a follow-up experiment (Experiment 2) was
      performed where a 4000 Hz pure tone was used as the CS+, and during the
      Generalization test, 2000 and 8000 Hz were used as GS. In both Experiment 1 and 2
      there was significant discrimination in US expectancy responses on all stimuli
      during the Generalization Test, indicating the stimuli were perceptually
      distinct. In Experiment 1, participants showed similar levels of fear-potentiated
      startle to the GS that were adjacent to the CS+, and discriminated between
      stimuli that were 2 or more degrees from the CS+. Experiment 2 demonstrated no
      fear-potentiated startle generalization. The current study is the first to use
      auditory cues to test generalization of conditioned fear responses; such cues may
      be especially relevant to combat posttraumatic stress disorder (PTSD) where much
      of the traumatic exposure may involve sounds. 

PMID- 25368560
TI  - Differences in social interaction- vs. cocaine reward in mouse vs. rat.
AB  - We previously developed rat experimental models based on the conditioned place
      preference (CPP) paradigm in which only four 15-min episodes of dyadic social
      interaction with a sex- and weight-matched male Sprague Dawley (SD) rat (1)
      reversed CPP from cocaine to social interaction despite continuing cocaine
      training, and (2) prevented the reacquisition/re-expression of cocaine CPP. In a
      concurrent conditioning schedule, pairing one compartment with social interaction
      and the other compartment with 15 mg/kg cocaine injections, rats spent the same
      amount of time in both compartments and the most rewarding sensory component of
      the composite stimulus social interaction was touch (taction). In the present
      study, we validated our experimental paradigm in C57BL/6 mice to investigate if
      our experimental paradigm may be useful for the considerable number of
      genetically modified mouse models. Only 71% of the tested mice developed place
      preference for social interaction, whereas 85% of the rats did. Accordingly, 29%
      of the mice developed conditioned place aversion (CPA) to social interaction,
      whereas this was true for only 15% of the rats. In support of the lesser
      likelihood of mice to develop a preference for social interaction, the average
      amount of time spent in direct contact was 17% for mice vs. 79% for rats. In
      animals that were concurrently conditioned for social interaction vs. cocaine,
      the relative reward strength for cocaine was 300-fold higher in mice than in
      rats. Considering that human addicts regularly prefer drugs of abuse to drug-free
      social interaction, the present findings suggest that our experimental paradigm
      of concurrent CPP for cocaine vs. social interaction is of even greater
      translational power if performed in C57BL/6 mice, the genetic background for most
      transgenic rodent models, than in rats. 

PMID- 25368556
TI  - Extracellular matrix control of dendritic spine and synapse structure and
      plasticity in adulthood.
AB  - Dendritic spines are the receptive contacts at most excitatory synapses in the
      central nervous system. Spines are dynamic in the developing brain, changing
      shape as they mature as well as appearing and disappearing as they make and break
      connections. Spines become much more stable in adulthood, and spine structure
      must be actively maintained to support established circuit function. At the same
      time, adult spines must retain some plasticity so their structure can be modified
      by activity and experience. As such, the regulation of spine stability and
      remodeling in the adult animal is critical for normal function, and disruption of
      these processes is associated with a variety of late onset diseases including
      schizophrenia and Alzheimer's disease. The extracellular matrix (ECM), composed
      of a meshwork of proteins and proteoglycans, is a critical regulator of spine and
      synapse stability and plasticity. While the role of ECM receptors in spine
      regulation has been extensively studied, considerably less research has focused
      directly on the role of specific ECM ligands. Here, we review the evidence for a
      role of several brain ECM ligands and remodeling proteases in the regulation of
      dendritic spine and synapse formation, plasticity, and stability in adults. 

PMID- 25368561
TI  - The behavior of larval zebrafish reveals stressor-mediated anorexia during early
      vertebrate development.
AB  - The relationship between stress and food consumption has been well documented in
      adults but less so in developing vertebrates. Here we demonstrate that an
      encounter with a stressor can suppress food consumption in larval zebrafish.
      Furthermore, we provide indication that food intake suppression cannot be
      accounted for by changes in locomotion, oxygen consumption and visual responses,
      as they remain unaffected after exposure to a potent stressor. We also show that
      feeding reoccurs when basal levels of cortisol (stress hormone in humans and
      teleosts) are re-established. The results present evidence that the onset of
      stress can switch off the drive for feeding very early in vertebrate development,
      and add a novel endpoint for analyses of metabolic and behavioral disorders in an
      organism suitable for high-throughput genetics and non-invasive brain imaging. 

PMID- 25368563
TI  - Different neural systems contribute to semantic bias and conflict detection in
      the inclusion fallacy task.
AB  - The inclusion fallacy is a phenomenon in which generalization from a specific
      premise category to a more general conclusion category is considered stronger
      than a generalization to a specific conclusion category nested within the more
      general set. Such inferences violate rational norms and are part of the reasoning
      fallacy literature that provides interesting tasks to explore cognitive and
      neural basis of reasoning. To explore the functional neuroanatomy of the
      inclusion fallacy, we used a 2 * 2 factorial design, with factors for
      quantification (explicit and implicit) and response (fallacious and non
      fallacious). It was found that a left fronto-temporal system, along with a
      superior medial frontal system, was specifically activated in response to
      fallacious responses consistent with a semantic biasing of judgment explanation.
      A right fronto-parietal system was specifically recruited in response to
      detecting conflict associated with the heightened fallacy condition. These
      results are largely consistent with previous studies of reasoning fallacy and
      support a multiple systems model of reasoning. 

PMID- 25368562
TI  - Potential self-regulatory mechanisms of yoga for psychological health.
AB  - Research suggesting the beneficial effects of yoga on myriad aspects of
      psychological health has proliferated in recent years, yet there is currently no
      overarching framework by which to understand yoga's potential beneficial effects.
      Here we provide a theoretical framework and systems-based network model of yoga
      that focuses on integration of top-down and bottom-up forms of self-regulation.
      We begin by contextualizing yoga in historical and contemporary settings, and
      then detail how specific components of yoga practice may affect cognitive,
      emotional, behavioral, and autonomic output under stress through an emphasis on
      interoception and bottom-up input, resulting in physical and psychological
      health. The model describes yoga practice as a comprehensive skillset of
      synergistic process tools that facilitate bidirectional feedback and integration
      between high- and low-level brain networks, and afferent and re-afferent input
      from interoceptive processes (somatosensory, viscerosensory, chemosensory). From
      a predictive coding perspective we propose a shift to perceptual inference for
      stress modulation and optimal self-regulation. We describe how the processes that
      sub-serve self-regulation become more automatized and efficient over time and
      practice, requiring less effort to initiate when necessary and terminate more
      rapidly when no longer needed. To support our proposed model, we present the
      available evidence for yoga affecting self-regulatory pathways, integrating
      existing constructs from behavior theory and cognitive neuroscience with emerging
      yoga and meditation research. This paper is intended to guide future basic and
      clinical research, specifically targeting areas of development in the treatment
      of stress-mediated psychological disorders. 

PMID- 25368565
TI  - Development of holistic vs. featural processing in face recognition.
AB  - According to a classic view developed by Carey and Diamond (1977), young children
      process faces in a piecemeal fashion before adult-like holistic processing starts
      to emerge at the age of around 10 years. This is known as the encoding switch
      hypothesis. Since then, a growing body of studies have challenged the theory.
      This article will provide a critical appraisal of this literature, followed by an
      analysis of some more recent developments. We will conclude, quite contrary to
      the classical view, that holistic processing is not only present in early child
      development, but could even precede the development of part-based processing. 

PMID- 25368564
TI  - Associations between Proprioceptive Neural Pathway Structural Connectivity and
      Balance in People with Multiple Sclerosis.
AB  - Mobility and balance impairments are a hallmark of multiple sclerosis (MS),
      affecting nearly half of patients at presentation and resulting in decreased
      activity and participation, falls, injuries, and reduced quality of life. A
      growing body of work suggests that balance impairments in people with mild MS are
      primarily the result of deficits in proprioception, the ability to determine body
      position in space in the absence of vision. A better understanding of the
      pathophysiology of balance disturbances in MS is needed to develop evidence-based
      rehabilitation approaches. The purpose of the current study was to (1) map the
      cortical proprioceptive pathway in vivo using diffusion-weighted imaging and (2)
      assess associations between proprioceptive pathway white matter microstructural
      integrity and performance on clinical and behavioral balance tasks. We
      hypothesized that people with MS (PwMS) would have reduced integrity of cerebral
      proprioceptive pathways, and that reduced white matter microstructure within
      these tracts would be strongly related to proprioceptive-based balance deficits.
      We found poorer balance control on proprioceptive-based tasks and reduced white
      matter microstructural integrity of the cortical proprioceptive tracts in PwMS
      compared with age-matched healthy controls (HC). Microstructural integrity of
      this pathway in the right hemisphere was also strongly associated with
      proprioceptive-based balance control in PwMS and controls. Conversely, while
      white matter integrity of the right hemisphere's proprioceptive pathway was
      significantly correlated with overall balance performance in HC, there was no
      such relationship in PwMS. These results augment existing literature suggesting
      that balance control in PwMS may become more dependent upon (1) cerebellar
      regulated proprioceptive control, (2) the vestibular system, and/or (3) the
      visual system. 

PMID- 25368566
TI  - Focal cortical thickness correlates of exceptional memory training in Vedic
      priests.
AB  - The capacity for semantic memory-the ability to acquire and store knowledge of
      the world-is highly developed in the human brain. In particular, semantic memory
      assimilated through an auditory route may be a uniquely human capacity. One
      method of obtaining neurobiological insight into memory mechanisms is through the
      study of experts. In this work, we study a group of Hindu Vedic priests, whose
      religious training requires the memorization of vast tracts of scriptural texts
      through an oral tradition, recalled spontaneously during a lifetime of subsequent
      spiritual practice. We demonstrate focal increases of cortical thickness in
      regions of the left prefrontal lobe and right temporal lobe in Vedic priests, in
      comparison to a group of matched controls. The findings are relevant to current
      hypotheses regarding cognitive processes underlying storage and recall of long
      term declarative memory. 

PMID- 25368567
TI  - Cochlear implantation (CI) for prelingual deafness: the relevance of studies of
      brain organization and the role of first language acquisition in considering
      outcome success.
AB  - Cochlear implantation (CI) for profound congenital hearing impairment, while
      often successful in restoring hearing to the deaf child, does not always result
      in effective speech processing. Exposure to non-auditory signals during the pre
      implantation period is widely held to be responsible for such failures. Here, we
      question the inference that such exposure irreparably distorts the function of
      auditory cortex, negatively impacting the efficacy of CI. Animal studies suggest
      that in congenital early deafness there is a disconnection between (disordered)
      activation in primary auditory cortex (A1) and activation in secondary auditory
      cortex (A2). In humans, one factor contributing to this functional decoupling is
      assumed to be abnormal activation of A1 by visual projections-including exposure
      to sign language. In this paper we show that that this abnormal activation of A1
      does not routinely occur, while A2 functions effectively supramodally and
      multimodally to deliver spoken language irrespective of hearing status. What,
      then, is responsible for poor outcomes for some individuals with CI and for
      apparent abnormalities in cortical organization in these people? Since infancy is
      a critical period for the acquisition of language, deaf children born to hearing
      parents are at risk of developing inefficient neural structures to support
      skilled language processing. A sign language, acquired by a deaf child as a first
      language in a signing environment, is cortically organized like a heard spoken
      language in terms of specialization of the dominant perisylvian system. However,
      very few deaf children are exposed to sign language in early infancy. Moreover,
      no studies to date have examined sign language proficiency in relation to
      cortical organization in individuals with CI. Given the paucity of such relevant
      findings, we suggest that the best guarantee of good language outcome after CI is
      the establishment of a secure first language pre-implant-however that may be
      achieved, and whatever the success of auditory restoration. 

PMID- 25368568
TI  - Real-world objects are more memorable than photographs of objects.
AB  - Research studies in psychology typically use two-dimensional (2D) images of
      objects as proxies for real-world three-dimensional (3D) stimuli. There are,
      however, a number of important differences between real objects and images that
      could influence cognition and behavior. Although human memory has been studied
      extensively, only a handful of studies have used real objects in the context of
      memory and virtually none have directly compared memory for real objects vs.
      their 2D counterparts. Here we examined whether or not episodic memory is
      influenced by the format in which objects are displayed. We conducted two
      experiments asking participants to freely recall, and to recognize, a set of 44
      common household objects. Critically, the exemplars were displayed to observers
      in one of three viewing conditions: real-world objects, colored photographs, or
      black and white line drawings. Stimuli were closely matched across conditions for
      size, orientation, and illumination. Surprisingly, recall and recognition
      performance was significantly better for real objects compared to colored
      photographs or line drawings (for which memory performance was equivalent). We
      replicated this pattern in a second experiment comparing memory for real objects
      vs. color photos, when the stimuli were matched for viewing angle across
      conditions. Again, recall and recognition performance was significantly better
      for the real objects than matched color photos of the same items. Taken together,
      our data suggest that real objects are more memorable than pictorial stimuli. Our
      results highlight the importance of studying real-world object cognition and
      raise the potential for applied use in developing effective strategies for
      education, marketing, and further research on object-related cognition. 

PMID- 25368570
TI  - Brightness/darkness induction and the genesis of a contour.
AB  - Visual contours often result from the integration or interpolation of fragmented
      edges. The strength of the completion increases when the edges share the same
      contrast polarity (CP). Here we demonstrate that the appearance in the perceptual
      field of this integrated unit, or contour of invariant CP, is concomitant with a
      vivid brightness alteration of the surfaces at its opposite sides. To observe
      this effect requires some stratagems because the formation in the visual field of
      a contour of invariant CP normally engenders the formation of a second contour
      and then the rise of two streams of induction signals that interfere in different
      ways. Particular configurations have been introduced that allow us to observe the
      induction effects of one contour taken in isolation. I documented these effects
      by phenomenological observations and psychophysical measurement of the brightness
      alteration in relation to luminance contrast. When the edges of the same CP
      complete to form a contour, the background of homogeneous luminance appears to
      dim at one side and to brighten at the opposite side (in accord with the CP). The
      strength of the phenomenon is proportional to the local luminance contrast. This
      effect weakens or nulls when the contour of the invariant CP separates surfaces
      filled with different gray shades. These conflicting results stimulate a deeper
      exploration of the induction phenomena and their role in the computation of
      brightness contrast. An alternative perspective is offered to account for some
      brightness illusions and their relation to the phenomenal transparency. The main
      assumption asserts that, when in the same region induction signals of opposite CP
      overlap, the filling-in is blocked unless the image is stratified into different
      layers, one for each signal of the same polarity. Phenomenological observations
      document this "solution" by the visual system. 

PMID- 25368569
TI  - Control of Leg Movements Driven by EMG Activity of Shoulder Muscles.
AB  - During human walking, there exists a functional neural coupling between arms and
      legs, and between cervical and lumbosacral pattern generators. Here, we present a
      novel approach for associating the electromyographic (EMG) activity from upper
      limb muscles with leg kinematics. Our methodology takes advantage of the high
      involvement of shoulder muscles in most locomotor-related movements and of the
      natural co-ordination between arms and legs. Nine healthy subjects were asked to
      walk at different constant and variable speeds (3-5 km/h), while EMG activity of
      shoulder (deltoid) muscles and the kinematics of walking were recorded. To ensure
      a high level of EMG activity in deltoid, the subjects performed slightly larger
      arm swinging than they usually do. The temporal structure of the burst-like EMG
      activity was used to predict the spatiotemporal kinematic pattern of the
      forthcoming step. A comparison of actual and predicted stride leg kinematics
      showed a high degree of correspondence (r > 0.9). This algorithm has been also
      implemented in pilot experiments for controlling avatar walking in a virtual
      reality setup and an exoskeleton during over-ground stepping. The proposed
      approach may have important implications for the design of human-machine
      interfaces and neuroprosthetic technologies such as those of assistive lower limb
      exoskeletons. 

PMID- 25368571
TI  - The use of virtual reality in craving assessment and cue-exposure therapy in
      substance use disorders.
AB  - Craving is recognized as an important diagnosis criterion for substance use
      disorders (SUDs) and a predictive factor of relapse. Various methods to study
      craving exist; however, suppressing craving to successfully promote abstinence
      remains an unmet clinical need in SUDs. One reason is that social and
      environmental contexts recalling drug and alcohol consumption in the everyday
      life of patients suffering from SUDs often initiate craving and provoke relapse.
      Current behavioral therapies for SUDs use the cue-exposure approach to suppress
      salience of social and environmental contexts that may induce craving. They
      facilitate learning and cognitive reinforcement of new behavior and entrain
      craving suppression in the presence of cues related to drug and alcohol
      consumption. Unfortunately, craving often overweighs behavioral training
      especially in real social and environmental contexts with peer pressure
      encouraging the use of substance, such as parties and bars. In this perspective,
      virtual reality (VR) is gaining interest in the development of cue-reactivity
      paradigms and practices new skills in treatment. VR enhances ecological validity
      of traditional craving-induction measurement. In this review, we discuss results
      from (1) studies using VR and alternative virtual agents in the induction of
      craving and (2) studies combining cue-exposure therapy with VR in the promotion
      of abstinence from drugs and alcohol use. They used virtual environments,
      displaying alcohol and drugs to SUD patients. Moreover, some environments
      included avatars. Hence, some studies have focused on the social interactions
      that are associated with drug-seeking behaviors and peer pressure. Findings
      indicate that VR can successfully increase craving. Studies combining cue
      exposure therapy with virtual environment, however, reported mitigated success so
      far. 

PMID- 25368572
TI  - Regional white matter damage predicts speech fluency in chronic post-stroke
      aphasia.
AB  - RECENTLY, TWO DIFFERENT WHITE MATTER REGIONS THAT SUPPORT SPEECH FLUENCY HAVE
      BEEN IDENTIFIED: the aslant tract and the anterior segment of the arcuate
      fasciculus (ASAF). The role of the ASAF was demonstrated in patients with post
      stroke aphasia, while the role of the aslant tract shown in primary progressive
      aphasia. Regional white matter integrity appears to be crucial for speech
      production; however, the degree that each region exerts an independent influence
      on speech fluency is unclear. Furthermore, it is not yet defined if damage to
      both white matter regions influences speech in the context of the same neural
      mechanism (stroke-induced aphasia). This study assessed the relationship between
      speech fluency and quantitative integrity of the aslant region and the ASAF. It
      also explored the relationship between speech fluency and other white matter
      regions underlying classic cortical language areas such as the uncinate
      fasciculus and the inferior longitudinal fasciculus (ILF). Damage to these
      regions, except the ILF, was associated with speech fluency, suggesting
      synergistic association of these regions with speech fluency in post-stroke
      aphasia. These observations support the theory that speech fluency requires the
      complex, orchestrated activity between a network of pre-motor, secondary, and
      tertiary associative cortices, supported in turn by regional white matter
      integrity. 

PMID- 25368573
TI  - Computational study of NMDA conductance and cortical oscillations in
      schizophrenia.
AB  - N-methyl-D-aspartate (NMDA) receptor hypofunction has been implicated in the
      pathophysiology of schizophrenia. The illness is also characterized by gamma
      oscillatory disturbances, which can be evaluated with precise frequency
      specificity employing auditory cortical entrainment paradigms. This computational
      study investigates how synaptic NMDA hypofunction may give rise to network level
      oscillatory deficits as indexed by entrainment paradigms. We developed a
      computational model of a local cortical circuit with pyramidal cells and fast
      spiking interneurons (FSI), incorporating NMDA, alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic (AMPA), and gamma-aminobutyric acid (GABA) synaptic kinetics.
      We evaluated the effects of varying NMDA conductance on FSIs and pyramidal cells,
      as well as AMPA to NMDA ratio. We also examined the differential effects across a
      broad range of entrainment frequencies as a function of NMDA conductance. Varying
      NMDA conductance onto FSIs revealed an inverted-U relation with network gamma
      whereas NMDA conductance onto the pyramidal cells had a more monotonic
      relationship. Varying NMDA vs. AMPA conductance onto FSIs demonstrated the
      necessity of AMPA in the generation of gamma while NMDA receptors had a
      modulatory role. Finally, reducing NMDA conductance onto FSI and varying the
      stimulus input frequency reproduced the specific reductions in gamma range (~40
      Hz) as observed in schizophrenia studies. Our computational study showed that
      reductions in NMDA conductance onto FSIs can reproduce similar disturbances in
      entrainment to periodic stimuli within the gamma range as reported in
      schizophrenia studies. These findings provide a mechanistic account of how
      specific cellular level disturbances can give rise to circuitry level
      pathophysiologic disturbance in schizophrenia. 

PMID- 25368574
TI  - Integrative analysis of multi-dimensional imaging genomics data for Alzheimer's
      disease prediction.
AB  - In this paper, we explore the effects of integrating multi-dimensional imaging
      genomics data for Alzheimer's disease (AD) prediction using machine learning
      approaches. Precisely, we compare our three recent proposed feature selection
      methods [i.e., multiple kernel learning (MKL), high-order graph matching based
      feature selection (HGM-FS), sparse multimodal learning (SMML)] using four widely
      used modalities [i.e., magnetic resonance imaging (MRI), positron emission
      tomography (PET), cerebrospinal fluid (CSF), and genetic modality single
      nucleotide polymorphism (SNP)]. This study demonstrates the performance of each
      method using these modalities individually or integratively, and may be valuable
      to clinical tests in practice. Our experimental results suggest that for AD
      prediction, in general, (1) in terms of accuracy, PET is the best modality; (2)
      Even though the discriminant power of genetic SNP features is weak, adding this
      modality to other modalities does help improve the classification accuracy; (3)
      HGM-FS works best among the three feature selection methods; (4) Some of the
      selected features are shared by all the feature selection methods, which may have
      high correlation with the disease. Using all the modalities on the Alzheimer's
      Disease Neuroimaging Initiative (ADNI) dataset, the best accuracies, described as
      (mean +/- standard deviation)%, among the three methods are (76.2 +/- 11.3)% for
      AD vs. MCI, (94.8 +/- 7.3)% for AD vs. HC, (76.5 +/- 11.1)% for MCI vs. HC, and
      (71.0 +/- 8.4)% for AD vs. MCI vs. HC, respectively. 

PMID- 25368575
TI  - Nutrition and prevention of Alzheimer's dementia.
AB  - A nutritional approach to prevent, slow, or halt the progression of disease is a
      promising strategy that has been widely investigated. Much epidemiologic data
      suggests that nutritional intake may influence the development and progression of
      Alzheimer's dementia (AD). Modifiable, environmental causes of AD include
      potential metabolic derangements caused by dietary insufficiency and or excess
      that may be corrected by nutritional supplementation and or dietary modification.
      Many nutritional supplements contain a myriad of health promoting constituents
      (anti-oxidants, vitamins, trace minerals, flavonoids, lipids, ...etc.) that may
      have novel mechanisms of action affecting cellular health and regeneration, the
      aging process itself, or may specifically disrupt pathogenic pathways in the
      development of AD. Nutritional modifications have the advantage of being cost
      effective, easy to implement, socially acceptable and generally safe and devoid
      of significant adverse events in most cases. Many nutritional interventions have
      been studied and continue to be evaluated in hopes of finding a successful agent,
      combination of agents, or dietary modifications that can be used for the
      prevention and or treatment of AD. The current review focuses on several key
      nutritional compounds and dietary modifications that have been studied in humans,
      and further discusses the rationale underlying their potential utility for the
      prevention and treatment of AD. 

PMID- 25368576
TI  - Age-related increases in false recognition: the role of perceptual and conceptual
      similarity.
AB  - Older adults (OAs) are more likely to falsely recognize novel events than young
      adults, and recent behavioral and neuroimaging evidence points to a reduced
      ability to distinguish overlapping information due to decline in hippocampal
      pattern separation. However, other data suggest a critical role for semantic
      similarity. Koutstaal et al. [(2003) false recognition of abstract vs. common
      objects in older and younger adults: testing the semantic categorization account,
      J. Exp. Psychol. Learn. 29, 499-510] reported that OAs were only vulnerable to
      false recognition of items with pre-existing semantic representations. We
      replicated Koutstaal et al.'s (2003) second experiment and examined the influence
      of independently rated perceptual and conceptual similarity between stimuli and
      lures. At study, young and OAs judged the pleasantness of pictures of abstract
      (unfamiliar) and concrete (familiar) items, followed by a surprise recognition
      test including studied items, similar lures, and novel unrelated items.
      Experiment 1 used dichotomous "old/new" responses at test, while in Experiment 2
      participants were also asked to judge lures as "similar," to increase explicit
      demands on pattern separation. In both experiments, OAs showed a greater increase
      in false recognition for concrete than abstract items relative to the young,
      replicating Koutstaal et al.'s (2003) findings. However, unlike in the earlier
      study, there was also an age-related increase in false recognition of abstract
      lures when multiple similar images had been studied. In line with pattern
      separation accounts of false recognition, OAs were more likely to misclassify
      concrete lures with high and moderate, but not low degrees of rated similarity to
      studied items. Results are consistent with the view that OAs are particularly
      susceptible to semantic interference in recognition memory, and with the
      possibility that this reflects age-related decline in pattern separation. 

PMID- 25368577
TI  - Noninvasive stimulation of prefrontal cortex strengthens existing episodic
      memories and reduces forgetting in the elderly.
AB  - Memory consolidation is a dynamic process. Reactivation of consolidated memories
      by a reminder triggers reconsolidation, a time-limited period during which
      existing memories can be modified (i.e., weakened or strengthened). Episodic
      memory refers to our ability to recall specific past events about what happened,
      including where and when. Difficulties in this form of long-term memory commonly
      occur in healthy aging. Because episodic memory is critical for daily life
      functioning, the development of effective interventions to reduce memory loss in
      elderly individuals is of great importance. Previous studies in young adults
      showed that the dorsolateral prefrontal cortex (DLPFC) plays a causal role in
      strengthening of verbal episodic memories through reconsolidation. The aim of the
      present study was to explore the extent to which facilitatory transcranial direct
      current stimulation (anodal tDCS) over the left DLPFC would strengthen existing
      episodic memories through reconsolidation in elderly individuals. On Day 1, older
      adults learned a list of 20 words. On Day 2 (24 h later), they received a
      reminder or not, and after 10 min tDCS was applied over the left DLPFC. Memory
      recall was tested on Day 3 (48 h later) and Day 30 (1 month later). Surprisingly,
      anodal tDCS over the left DLPFC (i.e., with or without the reminder) strengthened
      existing verbal episodic memories and reduced forgetting compared to sham
      stimulation. These results provide a framework for testing the hypothesis that
      facilitatory tDCS of left DLPFC might strengthen existing episodic memories and
      reduce memory loss in older adults with amnestic mild cognitive impairment. 

PMID- 25368579
TI  - Effects of berberine and red yeast on proinflammatory cytokines IL-6 and TNF
      alpha in peripheral blood mononuclear cells (PBMCs) of human subjects.
AB  - BACKGROUND AND AIMS: Obesity is a condition associated with chronic or acute
      inflammatory response characterized by an increase of proinflammatory cytokine
      levels. Peripheral blood mononuclear cells (PBMCs) migrate in adipose tissue
      inducing synthesis and secretion of adipocytokines as IL-6 and TNF-alpha. The aim
      of this study was to investigate the effect of berberine (a natural alkaloid) and
      red yeast (a natural antioxidant) on IL-6 and TNF-alpha cytokines release and
      gene expression, in circulating lipopolisaccarides (LPS) stimulated PBMCs.
      METHODS AND RESULTS: PBMCs isolated from whole blood of healthy donors were
      stimulated with LPS to induce cytokines production; simultaneously cells were
      treated with increasing doses of berberine and red yeast. The substances were
      administered alone or in association. IL-6 and TNF-alpha protein levels in the
      culture medium and their mRNA levels were assessed by ELISA and real time PCR,
      respectively. Berberine and red yeast treatment prevented the LPS induction of IL
      6 release in the culture medium of PBMCs. In addition, berberine plus red yeast
      treatment showed a synergic inhibitory effect on IL-6 release at low
      concentration. Berberine and red yeast showed an inhibitory effect also on LPS
      induction of TNF-alpha release exerting a synergic effect mainly at high
      concentrations. On the contrary, berberine and red yeast did not significantly
      affect IL-6 and TNF-alpha mRNA levels induced by LPS. In this case, only
      concomitant treatment of PBMCs with high doses of berberine and red yeast
      inhibits LPS induced IL-6 or TNF-alpha mRNA levels. CONCLUSIONS: The results of
      our study show that both berberine and red yeast were able to carry out anti
      inflammatory action through an inhibition of proinflammatory IL-6 and TNF-alpha
      protein release. Moreover, when given in combination these substances were able
      to inhibit IL-6 and TNF-alpha gene expression in PBMCs activated by LPS.
      Therefore, these substances could represent a useful pharmacological treatment to
      reduce the proinflammatory status accompanied with obesity.

PMID- 25368578
TI  - New therapeutic approaches for Alzheimer's disease and cerebral amyloid
      angiopathy.
AB  - Accumulating evidence has shown a strong relationship between Alzheimer's disease
      (AD), cerebral amyloid angiopathy (CAA), and cerebrovascular disease. Cognitive
      impairment in AD patients can result from cortical microinfarcts associated with
      CAA, as well as the synaptic and neuronal disturbances caused by cerebral
      accumulations of beta-amyloid (Abeta) and tau proteins. The pathophysiology of AD
      may lead to a toxic chain of events consisting of Abeta overproduction, impaired
      Abeta clearance, and brain ischemia. Insufficient removal of Abeta leads to
      development of CAA and plays a crucial role in sporadic AD cases, implicating
      promotion of Abeta clearance as an important therapeutic strategy. Abeta is
      mainly eliminated by three mechanisms: (1) enzymatic/glial degradation, (2)
      transcytotic delivery, and (3) perivascular drainage (3-"d" mechanisms).
      Enzymatic degradation may be facilitated by activation of Abeta-degrading enzymes
      such as neprilysin, angiotensin-converting enzyme, and insulin-degrading enzyme.
      Transcytotic delivery can be promoted by inhibition of the receptor for advanced
      glycation end products (RAGE), which mediates transcytotic influx of circulating
      Abeta into brain. Successful use of the RAGE inhibitor TTP488 in Phase II testing
      has led to a Phase III clinical trial for AD patients. The perivascular drainage
      system seems to be driven by motive force generated by cerebral arterial
      pulsations, suggesting that vasoactive drugs can facilitate Abeta clearance. One
      of the drugs promoting this system is cilostazol, a selective inhibitor of type 3
      phosphodiesterase. The clearance of fluorescent soluble Abeta tracers was
      significantly enhanced in cilostazol-treated CAA model mice. Given that the
      balance between Abeta synthesis and clearance determines brain Abeta
      accumulation, and that Abeta is cleared by several pathways stated above, multi
      drugs combination therapy could provide a mainstream cure for sporadic AD. 

PMID- 25368580
TI  - Functional cardiac imaging by random access microscopy.
AB  - Advances in the development of voltage sensitive dyes and Ca(2+) sensors in
      combination with innovative microscopy techniques allowed researchers to perform
      functional measurements with an unprecedented spatial and temporal resolution. At
      the moment, one of the shortcomings of available technologies is their
      incapability of imaging multiple fast phenomena while controlling the biological
      determinants involved. In the near future, ultrafast deflectors can be used to
      rapidly scan laser beams across the sample, performing optical measurements of
      action potential and Ca(2+) release from multiple sites within cardiac cells and
      tissues. The same scanning modality could also be used to control local Ca(2+)
      release and membrane electrical activity by activation of caged compounds and
      light-gated ion channels. With this approach, local Ca(2+) or voltage
      perturbations could be induced, simulating arrhythmogenic events, and their
      impact on physiological cell activity could be explored. The development of this
      optical methodology will provide fundamental insights in cardiac disease,
      boosting new therapeutic strategies, and, more generally, it will represent a new
      approach for the investigation of the physiology of excitable cells. 

PMID- 25368581
TI  - Role of the intercalated disc in cardiac propagation and arrhythmogenesis.
AB  - This review article discusses mechanisms underlying impulse propagation in
      cardiac muscle with specific emphasis on the role of the cardiac cell-to-cell
      junction, called the "intercalated disc."The first part of this review deals with
      the role of gap junction channels, formed by connexin proteins, as a determinant
      of impulse propagation. It is shown that, depending on the underlying structure
      of the cellular network, decreasing the conductance of gap junction channels (so
      called "electrical uncoupling") may either only slow, or additionally stabilize
      propagation and reverse unidirectional propagation block to bidirectional
      propagation. This is because the safety factor for propagation increases with
      decreasing intercellular electrical conductance. The role of heterogeneous
      connexin expression, which may be present in disease states, is also discussed.
      The hypothesis that so-called ephaptic impulse transmission plays a role in heart
      and can substitute for electrical coupling has been revived recently. Whereas
      ephaptic transmission can be demonstrated in theoretical simulations, direct
      experimental evidence has not yet been presented. The second part of this review
      deals with the interaction of three protein complexes at the intercalated disc:
      (1) desmosomal and adherens junction proteins, (2) ion channel proteins, and (3)
      gap junction channels consisting of connexins. Recent work has revealed multiple
      interactions between these three protein complexes which occur, at least in part,
      at the level of protein trafficking. Such interactions are likely to play an
      important role in the pathogenesis of arrhythmogenic cardiomyopathy, and may
      reveal new therapeutic concepts and targets. 

PMID- 25368582
TI  - Non-Chemical Distant Cellular Interactions as a potential confounder of cell
      biology experiments.
AB  - Distant cells can communicate with each other through a variety of methods. Two
      such methods involve electrical and/or chemical mechanisms. Non-chemical, distant
      cellular interactions may be another method of communication that cells can use
      to modify the behavior of other cells that are mechanically separated. Moreover,
      non-chemical, distant cellular interactions may explain some cases of confounding
      effects in Cell Biology experiments. In this article, we review non-chemical,
      distant cellular interactions studies to try to shed light on the mechanisms in
      this highly unconventional field of cell biology. Despite the existence of
      several theories that try to explain the mechanism of non-chemical, distant
      cellular interactions, this phenomenon is still speculative. Among candidate
      mechanisms, electromagnetic waves appear to have the most experimental support.
      In this brief article, we try to answer a few key questions that may further
      clarify this mechanism. 

PMID- 25368583
TI  - Hemichannels; from the molecule to the function.

PMID- 25368584
TI  - Endocannabinoid 2-Arachidonoylglycerol Self-Administration by Sprague-Dawley Rats
      and Stimulation of in vivo Dopamine Transmission in the Nucleus Accumbens Shell.
AB  - 2-Arachidonoylglycerol (2-AG) is the most potent endogenous ligand of brain
      cannabinoid CB1 receptors and is synthesized on demand from 2-arachidonate
      containing phosphoinositides by the action of diacylglycerol lipase in response
      to increased intracellular calcium. Several studies indicate that the
      endocannabinoid (eCB) system is involved in the mechanism of reward and that
      diverse drugs of abuse increase brain eCB levels. In addition, eCB are self
      administered (SA) by squirrel monkeys, and anandamide increases nucleus accumbens
      (NAc) shell dopamine (DA) in rats. To date, there is no evidence on the
      reinforcing effects of 2-AG and its effects on DA transmission in rodents. In
      order to fill this gap, we studied intravenous 2-AG SA and monitored the effect
      of 2-AG on extracellular DA in the NAc shell and core via microdialysis in male
      Sprague-Dawley rats. Rats were implanted with jugular catheters and trained to
      self-administer 2-AG [25 mg/kg/inf intravenously (iv)] in single daily 1 h
      sessions for 5 weeks under initial fixed ratio (FR) 1 schedule. The ratio was
      subsequently increased to FR2. Active nose poking increased from the 6th SA
      session (acquisition phase) but no significant increase of nose pokes was
      observed after FR2. When 2-AG was substituted for vehicle (25th SA session,
      extinction phase), rate responding as well as number of injections slowly
      decreased. When vehicle was replaced with 2-AG, SA behavior immediately recovered
      (reacquisition phase). The reinforcing effects of 2-AG in SA behavior were fully
      blocked by the CB1 receptor inverse agonist/antagonist rimonabant (1 mg/kg
      intraperitoneally, 30 min before SA session). In the microdialysis studies, we
      observed that 2-AG (0.1-1.0 mg/kg iv) preferentially stimulates NAc shell as
      compared to the NAc core. NAc shell DA increased by about 25% over basal value at
      the highest doses tested (0.5 and 1.0 mg/kg iv). The results obtained suggest
      that the eCB system, via 2-AG, plays an important role in reward. 

PMID- 25368585
TI  - Repeated exposure to conditioned fear stress increases anxiety and delays sleep
      recovery following exposure to an acute traumatic stressor.
AB  - Repeated stressor exposure can sensitize physiological responses to novel
      stressors and facilitate the development of stress-related psychiatric disorders
      including anxiety. Disruptions in diurnal rhythms of sleep-wake behavior
      accompany stress-related psychiatric disorders and could contribute to their
      development. Complex stressors that include fear-eliciting stimuli can be a
      component of repeated stress experienced by human beings, but whether exposure to
      repeated fear can prime the development of anxiety and sleep disturbances is
      unknown. In the current study, adult male F344 rats were exposed to either
      control conditions or repeated contextual fear conditioning for 22 days followed
      by exposure to no, mild (10), or severe (100) acute uncontrollable tail shock
      stress. Exposure to acute stress produced anxiety-like behavior as measured by a
      reduction in juvenile social exploration and exaggerated shock-elicited freezing
      in a novel context. Prior exposure to repeated fear enhanced anxiety-like
      behavior as measured by shock-elicited freezing, but did not alter social
      exploratory behavior. The potentiation of anxiety produced by prior repeated fear
      was temporary; exaggerated fear was present 1 day but not 4 days following acute
      stress. Interestingly, exposure to acute stress reduced rapid eye movement (REM)
      and non-REM (NREM) sleep during the hours immediately following acute stress.
      This initial reduction in sleep was followed by robust REM rebound and diurnal
      rhythm flattening of sleep/wake behavior. Prior repeated fear extended the acute
      stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the
      flattening of the diurnal rhythm of NREM sleep following acute stressor exposure.
      These data suggest that impaired recovery of sleep/wake behavior following acute
      stress could contribute to the mechanisms by which a history of prior repeated
      stress increases vulnerability to subsequent novel stressors and stress-related
      disorders. 

PMID- 25368587
TI  - Tactile feedback improves auditory spatial localization.
AB  - Our recent studies suggest that congenitally blind adults have severely impaired
      thresholds in an auditory spatial bisection task, pointing to the importance of
      vision in constructing complex auditory spatial maps (Gori et al., 2014). To
      explore strategies that may improve the auditory spatial sense in visually
      impaired people, we investigated the impact of tactile feedback on spatial
      auditory localization in 48 blindfolded sighted subjects. We measured auditory
      spatial bisection thresholds before and after training, either with tactile
      feedback, verbal feedback, or no feedback. Audio thresholds were first measured
      with a spatial bisection task: subjects judged whether the second sound of a
      three sound sequence was spatially closer to the first or the third sound. The
      tactile feedback group underwent two audio-tactile feedback sessions of 100
      trials, where each auditory trial was followed by the same spatial sequence
      played on the subject's forearm; auditory spatial bisection thresholds were
      evaluated after each session. In the verbal feedback condition, the positions of
      the sounds were verbally reported to the subject after each feedback trial. The
      no feedback group did the same sequence of trials, with no feedback. Performance
      improved significantly only after audio-tactile feedback. The results suggest
      that direct tactile feedback interacts with the auditory spatial localization
      system, possibly by a process of cross-sensory recalibration. Control tests with
      the subject rotated suggested that this effect occurs only when the tactile and
      acoustic sequences are spatially congruent. Our results suggest that the tactile
      system can be used to recalibrate the auditory sense of space. These results
      encourage the possibility of designing rehabilitation programs to help blind
      persons establish a robust auditory sense of space, through training with the
      tactile modality. 

PMID- 25368586
TI  - Body weight status, eating behavior, sensitivity to reward/punishment, and
      gender: relationships and interdependencies.
AB  - Behavioral and personality characteristics are factors that may jointly regulate
      body weight. This study explored the relationship between body mass index (BMI)
      and self-reported behavioral and personality measures. These measures included
      eating behavior (based on the Three-Factor Eating Questionnaire; Stunkard and
      Messick, 1985), sensitivity to reward and punishment (based on the Behavioral
      Inhibition System/Behavioral Activation System (BIS/BAS) scales) (Carver and
      White, 1994) and self-reported impulsivity (based on the Barratt Impulsiveness
      Scale-11; Patton et al., 1995). We found an inverted U-shaped relationship
      between restrained eating and BMI. This relationship was moderated by the level
      of disinhibited eating. Independent of eating behavior, BIS and BAS
      responsiveness were associated with BMI in a gender-specific manner with negative
      relationships for men and positive relationships for women. Together, eating
      behavior and BIS/BAS responsiveness accounted for a substantial proportion of BMI
      variance (men: ~25%, women: ~32%). A direct relationship between self-reported
      impulsivity and BMI was not observed. In summary, our results demonstrate a
      system of linear and non-linear relationships between the investigated factors
      and BMI. Moreover, body weight status was not only associated with eating
      behavior (cognitive restraint and disinhibition), but also with personality
      factors not inherently related to an eating context (BIS/BAS). Importantly, these
      relationships differ between men and women. 

PMID- 25368588
TI  - From ethics of care to psychology of care: reconnecting ethics of care to
      contemporary moral psychology.
AB  - Moral psychology once regarded ethics of care as a promising theory. However,
      there is evidence to suggest that nowadays moral psychology completely ignores
      ethics of care's various insights. Moreover, ethics of care's core concepts -
      compassion, dependence, and the importance of early relations to moral
      development- are no longer considered to be relevant to the development of new
      theories in the field. In this paper, I will firstly discuss some of the reasons
      which, over recent years, have contributed to the marginalization of the role of
      ethics of care in moral psychology. Next, I will show that ethics of care's most
      promising idea centered on the care given to an infant and the importance of that
      care to the development of moral thinking. In this context, I will be describing
      the implications of John Bowlby's attachment theories, infant research, findings
      in moral psychology and neuroscience. I will argue that ethics of care needs to
      be radically re-thought and replaced by a psychology of care, an attachment
      approach to moral judgment, which would establish the centrality of the
      caregiver's role in moral development. The philosophical implications of this
      approach to the understanding of the "rationalists" and "intuitionists" debate
      about the true nature of moral judgment is also discussed. 

PMID- 25368589
TI  - The intersubjective endeavor of psychopathology research: methodological
      reflections on a second-person perspective approach.
AB  - Research in psychopathology may be considered as an intersubjective endeavor
      mainly concerned with understanding other minds. Thus, the way we conceive of
      social understanding influences how we do research in psychology in the first
      place. In this paper, we focus on psychopathology research as a paradigmatic case
      for this methodological issue, since the relation between the researcher and the
      object of study is characterized by a major component of "otherness." We
      critically review different methodologies in psychopathology research,
      highlighting their relation to different social cognition theories (the third-,
      first-, and second-person approaches). Hence we outline the methodological
      implications arising from each theoretical stance. Firstly, we critically discuss
      the dominant paradigm in psychopathology research, based on the Diagnostic and
      Statistical Manual of Mental Disorders (American Psychiatric Association, 2013)
      and on quantitative methodology, as an example of a third-person methodology.
      Secondly, we contrast this mainstream view with phenomenological psychopathology
      which-by rejecting the reductionist view exclusively focused on behavioral
      symptoms-takes consciousness as its main object of study: it therefore attempts
      to grasp patients' first-person experience. But how can we speak about a first
      person perspective in psychopathology if the problem at stake is the experience
      of the other? How is it possible to understand the experience from "within," if
      the person who is having this experience is another? By addressing these issues,
      we critically explore the feasibility and usefulness of a second-person
      methodology in psychopathology research. Notwithstanding the importance of
      methodological pluralism, we argue that a second-person perspective should inform
      the epistemology and methods of research in psychopathology, as it recognizes the
      fundamental circular and intersubjective construction of knowledge. 

PMID- 25368590
TI  - The empirical study of norms is just what we are missing.
AB  - This paper argues that the goals people have when reasoning determine their own
      norms of reasoning. A radical descriptivism which avoids norms never worked for
      any science; nor can it work for the psychology of reasoning. Norms as we
      understand them are illustrated with examples from categorical syllogistic
      reasoning and the "new paradigm" of subjective probabilities. We argue that many
      formal systems are required for psychology: classical logic, non-monotonic
      logics, probability logics, relevance logic, and others. One of the hardest
      challenges is working out what goals reasoners have and choosing and tailoring
      the appropriate logics to model the norms those goals imply. 

PMID- 25368591
TI  - Language choice in bimodal bilingual development.
AB  - Bilingual children develop sensitivity to the language used by their
      interlocutors at an early age, reflected in differential use of each language by
      the child depending on their interlocutor. Factors such as discourse context and
      relative language dominance in the community may mediate the degree of language
      differentiation in preschool age children. Bimodal bilingual children, acquiring
      both a sign language and a spoken language, have an even more complex situation.
      Their Deaf parents vary considerably in access to the spoken language.
      Furthermore, in addition to code-mixing and code-switching, they use code
      blending-expressions in both speech and sign simultaneously-an option uniquely
      available to bimodal bilinguals. Code-blending is analogous to code-switching
      sociolinguistically, but is also a way to communicate without suppressing one
      language. For adult bimodal bilinguals, complete suppression of the non-selected
      language is cognitively demanding. We expect that bimodal bilingual children also
      find suppression difficult, and use blending rather than suppression in some
      contexts. We also expect relative community language dominance to be a factor in
      children's language choices. This study analyzes longitudinal spontaneous
      production data from four bimodal bilingual children and their Deaf and hearing
      interlocutors. Even at the earliest observations, the children produced more
      signed utterances with Deaf interlocutors and more speech with hearing
      interlocutors. However, while three of the four children produced >75% speech
      alone in speech target sessions, they produced <25% sign alone in sign target
      sessions. All four produced bimodal utterances in both, but more frequently in
      the sign sessions, potentially because they find suppression of the dominant
      language more difficult. Our results indicate that these children are sensitive
      to the language used by their interlocutors, while showing considerable influence
      from the dominant community language. 

PMID- 25368592
TI  - Syntactic flexibility and planning scope: the effect of verb bias on advance
      planning during sentence recall.
AB  - In sentence production, grammatical advance planning scope depends on contextual
      factors (e.g., time pressure), linguistic factors (e.g., ease of structural
      processing), and cognitive factors (e.g., production speed). The present study
      tests the influence of the availability of multiple syntactic alternatives (i.e.,
      syntactic flexibility) on the scope of advance planning during the recall of
      Dutch dative phrases. We manipulated syntactic flexibility by using verbs with a
      strong bias or a weak bias toward one structural alternative in sentence frames
      accepting both verbs (e.g., strong/weak bias: De ober schotelt/serveert de klant
      de maaltijd [voor] "The waiter dishes out/serves the customer the meal"). To
      assess lexical planning scope, we varied the frequency of the first post-verbal
      noun (N1, Experiment 1) or the second post-verbal noun (N2, Experiment 2). In
      each experiment, 36 speakers produced the verb phrases in a rapid serial visual
      presentation (RSVP) paradigm. On each trial, they read a sentence presented one
      word at a time, performed a short distractor task, and then saw a sentence
      preamble (e.g., De ober...) which they had to complete to form the presented
      sentence. Onset latencies were compared using linear mixed effects models. N1
      frequency did not produce any effects. N2 frequency only affected sentence onsets
      in the weak verb bias condition and especially in slow speakers. These findings
      highlight the dependency of planning scope during sentence recall on the
      grammatical properties of the verb and the frequency of post-verbal nouns.
      Implications for utterance planning in everyday speech are discussed. 

PMID- 25368593
TI  - Task conflict in the Stroop task: When Stroop interference decreases as Stroop
      facilitation increases in a low task conflict context.
AB  - In the present study participants completed two blocks of the Stroop task, one in
      which the response-stimulus interval (RSI) was 3500 ms and one in which RSI was
      200 ms. It was expected that, in line with previous research, the shorter RSI
      would induce a low Task Conflict context by increasing focus on the color
      identification goal in the Stroop task and lead to a novel finding of an increase
      in facilitation and simultaneous decrease in interference. Such a finding would
      be problematic for models of Stroop effects that predict these indices of
      performance should be affected in tandem. A crossover interaction is reported
      supporting these predictions. As predicted, the shorter RSI resulted in
      incongruent and congruent trial reaction times (RTs) decreasing relative to a
      static neutral baseline condition; hence interference decreased as facilitation
      increased. An explanatory model (expanding on the work of Goldfarb and Henik,
      2007) is presented that: (1) Shows how under certain conditions the predictions
      from single mechanism models hold true (i.e., when Task conflict is held
      constant); (2) Shows how it is possible that interference can be affected by an
      experimental manipulation that leaves facilitation apparently untouched; and (3)
      Predicts that facilitation cannot be independently affected by an experimental
      manipulation. 

PMID- 25368594
TI  - Processing different kinds of semantic relations in picture-word interference
      with non-masked and masked distractors.
AB  - Spoken production requires lexical selection, guided by the conceptual
      representation of the to-be-named target. Currently, the question whether lexical
      selection is subject to competition is hotly debated. In the picture-word
      interference task, manipulating the visibility of written distractor words
      provides important insights: clearly visible categorically related distractors
      cause interference whereas masked distractors induce facilitation (Finkbeiner and
      Caramazza, 2006). Now you see it, now you don't: On turning semantic interference
      into facilitation in a Stoop-like task. We explored the effect of distractor
      masking in more depth by investigating its interplay with different types of
      semantic overlap. Specifically, we contrasted categorical with associatively
      based relatedness. For the former, we replicated the polarity reversal in
      semantic effects dependent on whether distractors were masked or not. Post
      experimental visibility tests showed that weak semantic facilitation with masked
      distractors did not depend on individual variability in participants' ability to
      perceive the distractors. Associatively related distractors showed facilitation
      with non-masked presentation, but little effect when masked. Overall, the results
      suggest that it is primarily distractor activation strength which determines
      whether semantic effects are facilitatory or interfering in PWI tasks. 

PMID- 25368595
TI  - On the temporality of creative insight: a psychological and phenomenological
      perspective.
AB  - Research into creative insight has had a strong emphasis on the psychological
      processes underlying problem-solving situations as a standard model for the
      empirical study of this phenomenon. Although this model has produced significant
      advances in our scientific understanding of the nature of insight, we believe
      that a full comprehension of insight requires complementing cognitive and
      neuroscientific studies with a descriptive, first-person, phenomenological
      approach into how creative insight is experienced. Here we propose to take such
      first-person perspective while paying special attention to the temporal aspects
      of this experience. When this first-person perspective is taken into account, a
      dynamic past-future interplay can be identified at the core of the experience of
      creative insight, a structure that is compatible with both biological and
      biographical evidences. We believe this approach could complement and help bring
      together biological and psychological perspectives. Furthermore, we argue that
      because of its spontaneous but recurrent nature, creative insight could represent
      a relevant target for the phenomenological investigation of the flow of
      experience itself. 

PMID- 25368596
TI  - Extended stereopsis evaluation of professional and amateur soccer players and
      subjects without soccer background.
AB  - Stereopsis is one of several visual depth cues. It has been evaluated for
      athletes of different types of sports in the past. However, most studies do not
      cover the full range of stereopsis performance. Therefore, we propose computer
      supported stereopsis tests that provide an extended assessment and analysis of
      stereopsis performance including stereo acuity and response times. By providing
      stationary and moving stimuli they cover static and dynamic stereopsis,
      respectively. The proposed stereopsis tests were used to compare professional and
      amateur soccer players with subjects without soccer background. The soccer
      players could not perform significantly (p <= 0.05) superior than the subjects
      without soccer background. However, the soccer players showed significantly (p <=
      0.01) superior choice reaction times for monocular stimuli. The results are in
      congruence with previous findings in literature. 

PMID- 25368597
TI  - Perceptual learning in patients with macular degeneration.
AB  - Patients with age-related macular degeneration (AMD) or hereditary macular
      dystrophies (JMD) rely on an efficient use of their peripheral visual field. We
      trained eight AMD and five JMD patients to perform a texture-discrimination task
      (TDT) at their preferred retinal locus (PRL) used for fixation. Six training
      sessions of approximately one hour duration were conducted over a period of
      approximately 3 weeks. Before, during and after training twelve patients and
      twelve age-matched controls (the data from two controls had to be discarded
      later) took part in three functional magnetic resonance imaging (fMRI) sessions
      to assess training-related changes in the BOLD response in early visual cortex.
      Patients benefited from the training measurements as indexed by significant
      decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the
      presentation of the texture target on background and the visual mask, and in a
      significant location specific effect of the PRL with respect to hit rate (p =
      0.014). The following trends were observed: (i) improvement in Vernier acuity for
      an eccentric line-bisection task; (ii) positive correlation between the
      development of BOLD signals in early visual cortex and initial fixation stability
      (r = 0.531); (iii) positive correlation between the increase in task performance
      and initial fixation stability (r = 0.730). The first two trends were non
      significant, whereas the third trend was significant at p = 0.014, Bonferroni
      corrected. Consequently, our exploratory study suggests that training on the TDT
      can enhance eccentric vision in patients with central vision loss. This
      enhancement is accompanied by a modest alteration in the BOLD response in early
      visual cortex. 

PMID- 25368598
TI  - CI Therapy is Beneficial to Patients with Chronic Low-Functioning Hemiparesis
      after Stroke.
AB  - CI therapy is effective in patients with relatively good levels of residual arm
      function but its applicability to patients with low-functioning hemiparesis is
      not entirely clear. In the present study, we examined the feasibility and
      efficacy of the CI therapy concept in patients with very limited upper arm
      function prior to treatment, and further tested how the length of daily shaping
      training and constraining the good arm affects treatment outcome. In a baseline
      controlled design, 65 chronic patients were treated with 2 weeks of modified CI
      therapy. Patients were randomly allocated to four treatment groups receiving 90
      or 180 min of daily shaping training applied with or without constraint,
      respectively. Outcome was measured through the Reliable Change Index, which was
      calculated for parameters of motor function, health, and psychological wellbeing.
      Follow-up data were collected at 6 and 12 months. Two analyses were conducted, a
      whole-group analysis across all 65 participants and a sub-group analysis
      contrasting the four treatment variants. The whole-group analysis showed a
      significant treatment effect, which was largely sustained after 1 year. The sub
      group analysis revealed a mixed picture; while improvements against the baseline
      period were observed in all four subgroups, 180 min of daily shaping training
      coupled with the constraint yielded better outcome on the MAL but not the WMFT,
      while for 90 min of training the level of improvement was similar for those who
      wore the constraint and those who did not. Together these results suggest that,
      at least in those patients available for follow-up measures, modified CI therapy
      induces sustained improvements in motor function in patients with chronic low
      functioning hemiparesis. The absence of clear differences between the four
      treatment variants points to a complex relationship between the length of daily
      shaping training and the constraint in this patient group, which is likely to be
      mediated by fatigue and/or compliance with the constraint. 

PMID- 25368600
TI  - Human brain physiology investigated in the disorder of consciousness.

PMID- 25368599
TI  - Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and
      REM Sleep.
AB  - The pedunculopontine nucleus (PPN) is a major component of the reticular
      activating system (RAS) that regulates waking and REM sleep, states of high
      frequency EEG activity. Recently, we described the presence of high threshold,
      voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve
      gamma band oscillations in the mesopontine PPN, intralaminar parafascicular
      nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma
      band activity participates in sensory perception, problem solving, and memory.
      Rather than participating in the temporal binding of sensory events as in the
      cortex, gamma band activity in the RAS may participate in the processes of
      preconscious awareness, and provide the essential stream of information for the
      formulation of many of our actions. That is, the RAS may play an early permissive
      role in volition. Our latest results suggest that (1) the manifestation of gamma
      band activity during waking may employ a separate intracellular pathway compared
      to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is
      over expressed in schizophrenia and bipolar disorder, modulates gamma band
      oscillations in the PPN in a concentration-dependent manner, (3) leptin, which
      undergoes resistance in obesity resulting in sleep dysregulation, decreases
      sodium currents in PPN neurons, accounting for its normal attenuation of waking,
      and (4) following our discovery of electrical coupling in the RAS, we hypothesize
      that there are cell clusters within the PPN that may act in concert. These
      results provide novel information on the mechanisms controlling high-frequency
      activity related to waking and REM sleep by elements of the RAS. 

PMID- 25368601
TI  - Penfield's Prediction: A Mechanism for Deep Brain Stimulation.
AB  - CONTEXT: Despite its widespread use, the precise mechanism of action of Deep
      Brain Stimulation (DBS) therapy remains unknown. The modern urgency to publish
      more and new data can obscure previously learned lessons by the giants who have
      preceded us and whose shoulders we now stand upon. Wilder Penfield extensively
      studied the effects of artificial electrical brain stimulation and his comments
      on the subject are still very relevant today. In particular, he noted two very
      different (and seemingly opposite) effects of stimulation within the human brain.
      In some structures, artificial electrical stimulation has an effect, which mimics
      ablation, while, in other structures, it produces a stimulatory effect on that
      tissue. HYPOTHESIS: The hypothesis of this paper is fourfold. First, it proposes
      that some neural circuits are widely synchronized with other neural circuits,
      while some neural circuits are unsynchronized and operate independently. Second,
      it proposes that artificial high-frequency electrical stimulation of a
      synchronized neural circuit results in an ablative effect, but artificial high
      frequency electrical stimulation of an unsynchronized neural circuit results in a
      stimulatory effect. Third, it suggests a part of the mechanism by which large
      scale physiologic synchronization of widely distributed independently processed
      information streams may occur. This may be the neural mechanism underlying
      Penfield's "centrencephalic system," which he emphasized so many years ago.
      Fourth, it outlines the specific anatomic distribution of this physiologic
      synchronization, which Penfield has already clearly delineated as the
      distribution of his centrencephalic system. EVIDENCE: This paper draws on a brief
      overview of previous theory regarding the mechanism of action of DBS and on
      historical, as well as widely known modern clinical data regarding the observed
      effects of stimulation delivered to various targets within the brain. Basic
      science investigations, which support the hypothesis are also cited. CONCLUSION:
      This paper proposes a novel hypothesis for the mechanism of action of DBS, which
      was conceptually foreshadowed by Wilder Penfield decades ago.

PMID- 25368603
TI  - Pre-Operative, High-IL-6 Blood Level is a Risk Factor of Post-Operative Delirium
      Onset in Old Patients.
AB  - BACKGROUND: Post-operative delirium (POD) is a common complication in elderly
      patients undergoing surgery, but the underpinning causes are not clear. We
      hypothesized that inflammaging, the subclinical low and chronic grade
      inflammation characteristic of old people, can contribute to POD onset.
      Accordingly, we investigated the association of pre-operative and circulating
      cytokines in elderly patients (>65 years), admitted for elective and emergency
      surgery. METHODS: This is a secondary analysis of a sub-cohort of patients
      belonging to a previous large case-control study, where 351 patients were
      clinically and cognitively thoroughly characterized, together with the assessment
      of POD (47 patients) by confusion assessment method and delirium rating scale.
      Seventy-four pre-operative plasma samples were selected from a larger bio-bank
      and they included 37 subjects with POD and 37 without POD. Inflammaging related
      cytokines, i.e., IL-1beta, IL-2, IL-6, IL-8, IL-10, and TNF-alpha, were assayed
      by ELISA in pre-operative blood samples; univariate and multivariable analyses
      have been applied to identify cytokines independently associated to POD.
      Associations of cytokine levels with functional status, cognitive decline, intra
      hospital mortality, and comorbidity were also analyzed independently of POD
      onset. RESULTS: High IL-6 and low-IL-2 levels were significantly associated with
      POD. After adjustment for potential confounders in multivariate analysis, high
      level of pre-operative IL-6 was confirmed to be significantly associated with
      risk of POD onset. High level of IL-6 was also associated with several baseline
      features (including poor functional status, cognitive impairment, emergency
      admission, and higher comorbidity burden) and intra-hospital mortality.
      CONCLUSION: Pre-operative, high-plasma level of IL-6 (>=9 pg/mL) was
      significantly associated with POD onset. We propose IL-6 as an additional risk
      factor of POD onset together with the previously identified factors. Discovery of
      all risk factors contributing to POD onset will permit to improve hospitalized
      patient management and the decrease of healthcare cost.

PMID- 25368602
TI  - Thyroid Hormone-Regulated Cardiac microRNAs are Predicted to Suppress
      Pathological Hypertrophic Signaling.
AB  - Cardiomyocyte size in the healthy heart is in part determined by the level of
      circulating thyroid hormone (TH). Higher levels of TH induce ventricular
      hypertrophy, primarily in response to an increase in hemodynamic load. Normal
      cardiac function is maintained in this form of hypertrophy, whereas progressive
      contractile dysfunction is a hallmark of pathological hypertrophy. MicroRNAs
      (miRNAs) are important modulators of signal-transduction pathways driving adverse
      remodeling. Because little is known about the involvement of miRNAs in cardiac TH
      action and hypertrophy, we examined the miRNA expression profile of the
      hypertrophied left ventricle (LV) using a mouse model of TH-induced cardiac
      hypertrophy. C57Bl/6J mice were rendered hypothyroid by treatment with
      propylthiouracil and were subsequently treated for 3 days with TH (T3) or saline.
      T3 treatment increased LV weight by 38% (p < 0.05). RNA was isolated from the LV
      and expression of 641 mouse miRNAs was determined using Taqman Megaplex arrays.
      Data were analyzed using RQ-manager and DataAssist. A total of 52 T3-regulated
      miRNAs showing a >2-fold change (p < 0.05) were included in Ingenuity Pathway
      Analysis to predict target mRNAs involved in cardiac hypertrophy. The analysis
      was further restricted to proteins that have been validated as key factors in
      hypertrophic signal transduction in mouse models of ventricular remodeling. A
      total of 27 mRNAs were identified as bona fide targets. The predicted regulation
      of 19% of these targets indicates enhancement of physiological hypertrophy, while
      56% indicates suppression of pathological remodeling. Our data suggest that
      cardiac TH action includes a novel level of regulation in which a unique set of
      TH-dependent miRNAs primarily suppresses pathological hypertrophic signaling.
      This may be relevant for our understanding of the progression of adverse
      remodeling, since cardiac TH levels are known to decrease substantially in
      various forms of pathological hypertrophy. 

PMID- 25368604
TI  - Deletion of P58(IPK), the Cellular Inhibitor of the Protein Kinases PKR and PERK,
      Causes Bone Changes and Joint Degeneration in Mice.
AB  - OBJECTIVE: Protein kinase-like endoplasmic reticulum kinase (PERK) and protein
      kinase R (PKR) are implicated in endoplasmic reticulum stress-induced arthritis
      and pro-inflammatory cytokine-mediated cartilage degradation in vitro,
      respectively. We determined whether knockout of the cellular inhibitor of PERK
      and PKR, P58(IPK) causes joint degeneration in vivo and whether these molecules
      are activated in human osteoarthritis (OA). MATERIALS AND METHODS: Sections of
      knee joints from P58(IPK)-null and wild-type mice aged 12-13 and 23-25 months
      were stained with toluidine blue and scored for degeneration using the
      osteoarthritis research society international (OARSI) system. Bone changes were
      assessed by radiology and high-resolution micro-computed tomography of hind
      limbs. Sections from the medial tibial plateaus of two human knees, removed in
      total knee replacement surgery for OA, were immunolabelled for phosphorylated
      PERK and PKR and P58(IPK). RESULTS: Knockout mice exhibited narrower tibiae (p =
      0.0031) and smaller epiphyses in tibiae (p = 0.0004) and femora (p = 0.0214).
      Older knockout mice had reduced total volume inside the femoral periosteal
      envelope (p = 0.023), reduced tibial (p = 0.03), and femoral (p = 0.0012) bone
      volumes (BV) and reduced femoral BV fraction (p = 0.025). Compared with wild
      types, younger P58(IPK)-null mice had increased OARSI scores in medial femoral
      condyles (p = 0.035). Thirty four percent of null mice displayed severe joint
      degeneration with complete articular cartilage loss from the medial compartment
      and heterotopic chondro-osseous tissue in the medial joint capsule.
      Phosphorylated PERK and PKR were localized throughout human osteoarthritic tibial
      plateaus but, in particular, in areas exhibiting the most degeneration. There was
      limited expression of P58(IPK). CONCLUSION: This study is the first to reveal a
      critical role for P58(IPK) in maintaining joint integrity in vivo, implicating
      the PKR and PERK stress signaling pathways in bony changes underlying the
      pathogenesis of joint degeneration.

PMID- 25368605
TI  - Constitutional thinness and anorexia nervosa: a possible misdiagnosis?
AB  - Clinical and biological aspects of restrictive anorexia nervosa (R-AN) are well
      documented. More than 10,000 articles since 1911 and more than 600 in 2013 have
      addressed R-AN psychiatric, somatic, and biological aspects. Genetic background,
      ineffectiveness of appetite regulating hormones on refeeding process, bone loss,
      and place of amenorrhea in the definition are widely discussed and reviewed.
      Oppositely, constitutional thinness (CT) is an almost unknown entity. Only 32
      articles have been published on this topic since 1953. Similar symptoms
      associating low body mass index, low fat, and bone mass are reported in both CT
      and R-AN subjects. Conversely, menses are preserved in CT women and almost the
      entire hormonal profile is normal, except for leptin and PYY. The aim of the
      present review is to alert the clinician on the confusing clinical presentation
      of these two situations, a potential source of misdiagnosis, especially since R
      AN definition has changed in DSM5. 

PMID- 25368606
TI  - Phylogenetic signal in the community structure of host-specific microbiomes of
      tropical marine sponges.
AB  - Sponges (Porifera) can host diverse and abundant communities of microbial
      symbionts that make crucial contributions to host metabolism. Although these
      communities are often host-specific and hypothesized to co-evolve with their
      hosts, correlations between host phylogeny and microbiome community structure are
      rarely tested. As part of the Earth Microbiome Project (EMP), we surveyed the
      microbiomes associated with 20 species of tropical marine sponges collected over
      a narrow geographic range. We tested whether (1) univariate metrics of microbiome
      diversity displayed significant phylogenetic signal across the host phylogeny;
      (2) host identity and host phylogeny were significant factors in multivariate
      analyses of taxonomic and phylogenetic dissimilarity; and (3) different minimum
      read thresholds impacted these results. We observed significant differences in
      univariate metrics of diversity among host species for all read thresholds, with
      strong phylogenetic signal in the inverse Simpson's index of diversity (D). We
      observed a surprisingly wide range of variability in community dissimilarity
      within host species (4-73%); this variability was not related to microbial
      abundance within a host species. Taxonomic and phylogenetic dissimilarity were
      significantly impacted by host identity and host phylogeny when these factors
      were considered individually; when tested together, the effect of host phylogeny
      was reduced, but remained significant. In our dataset, this outcome is largely
      due to closely related host sponges harboring distinct microbial taxa. Host
      identity maintained a strong statistical signal at all minimum read thresholds.
      Although the identity of specific microbial taxa varied substantially among host
      sponges, closely related hosts tended to harbor microbial communities with
      similar patterns of relative abundance. We hypothesize that microbiomes with low
      D might be structured by regulation of the microbial community by the host or by
      the presence of competitively dominant symbionts that are themselves under
      selection for host specificity. 

PMID- 25368608
TI  - The Salmonella effector protein SpvC, a phosphothreonine lyase is functional in
      plant cells.
AB  - Salmonella is one of the most prominent causes of food poisoning and growing
      evidence indicates that contaminated fruits and vegetables are an increasing
      concern for human health. Successful infection demands the suppression of the
      host immune system, which is often achieved via injection of bacterial effector
      proteins into host cells. In this report we present the function of Salmonella
      effector protein in plant cell, supporting the new concept of trans-kingdom
      competence of this bacterium. We screened a range of Salmonella Typhimurium
      effector proteins for interference with plant immunity. Among these, the
      phosphothreonine lyase SpvC attenuated the induction of immunity-related genes
      when present in plant cells. Using in vitro and in vivo systems we show that this
      effector protein interacts with and dephosphorylates activated Arabidopsis
      Mitogen-activated Protein Kinase 6 (MPK6), thereby inhibiting defense signaling.
      Moreover, the requirement of Salmonella SpvC was shown by the decreased
      proliferation of the DeltaspvC mutant in Arabidopsis plants. These results
      suggest that some Salmonella effector proteins could have a conserved function
      during proliferation in different hosts. The fact that Salmonella and other
      Enterobacteriaceae use plants as hosts strongly suggests that plants represent a
      much larger reservoir for animal pathogens than so far estimated. 

PMID- 25368607
TI  - Variation on a theme; an overview of the Tn916/Tn1545 family of mobile genetic
      elements in the oral and nasopharyngeal streptococci.
AB  - The oral and nasopharyngeal streptococci are a major part of the normal
      microbiota in humans. Most human associated streptococci are considered
      commensals, however, a small number of them are pathogenic, causing a wide range
      of diseases including oral infections such as dental caries and periodontitis and
      diseases at other body sites including sinusitis and endocarditis, and in the
      case of Streptococcus pneumoniae, meningitis. Both phenotypic and sequence based
      studies have shown that the human associated streptococci from the mouth and
      nasopharynx harbor a large number of antibiotic resistance genes and these are
      often located on mobile genetic elements (MGEs) known as conjugative transposons
      or integrative and conjugative elements of the Tn916/Tn1545 family. These MGEs
      are responsible for the spread of the resistance genes between streptococci and
      also between streptococci and other bacteria. In this review we describe the
      resistances conferred by, and the genetic variations between the many different
      Tn916-like elements found in recent studies of oral and nasopharyngeal
      streptococci and show that Tn916-like elements are important mediators of
      antibiotic resistance genes within this genus. We will also discuss the role of
      the oral environment and how this is conducive to the transfer of these elements
      and discuss the contribution of both transformation and conjugation on the
      transfer and evolution of these elements in different streptococci. 

PMID- 25368609
TI  - Pathogen-derived biomarkers for active tuberculosis diagnosis.
AB  - Tuberculosis (TB) is an infectious disease caused by members of Mycobacterium
      tuberculosis complex. Despite the availability of effective treatments, TB
      remains a major public health concern in most low and middle-income countries,
      representing worldwide the second leading cause of death from an infectious
      disease. Inadequate case detection and failures to classify the disease status
      hamper proper TB control. The limitations of the conventional diagnostic methods
      have encouraged much research activities in this field, but there is still an
      urgent need for an accurate point of care test for active TB diagnosis. A rapid,
      precise, and inexpensive TB diagnostic test would allow an earlier implementation
      of an appropriate treatment and the reduction of disease transmission. Pathogen
      derived molecules present in clinical specimens of affected patients are being
      validated for that purpose. This short review aims to summarize the available
      data regarding biomarkers derived from M. tuberculosis, and their current usage
      in active TB diagnosis. 

PMID- 25368611
TI  - The role of toll-like receptors in colorectal cancer progression: evidence for
      epithelial to leucocytic transition.
AB  - Toll-like receptors (TLRs) are expressed by immune cells, intestinal epithelium,
      and tumor cells. In the homeostatic setting, they help to regulate control over
      invading pathogens and maintain the epithelial lining of the large and small
      intestines. Aberrant expression of certain TLRs by tumor cells can induce growth
      inhibition while others contribute to tumorigenesis and progression. Activation
      of these TLRs can induce inflammation, tumor cell proliferation, immune evasion,
      local invasion, and distant metastasis. These TLR-influenced behaviors have
      similarities with properties observed in leukocytes, suggesting that tumors may
      be hijacking immune programs to become more aggressive. The concept of epithelial
      to leucocytic-transition (ELT) is proposed, akin to epithelial to mesenchymal
      transition, in which tumors develop the ability to activate leucocytic traits
      otherwise inaccessible to epithelial cells. Understanding the mechanisms of ELT
      could lead to novel therapeutic strategies for inhibiting tumor metastasis. 

PMID- 25368610
TI  - A new strategy to fight antimicrobial resistance: the revival of old antibiotics.
AB  - The increasing prevalence of hospital and community-acquired infections caused by
      multidrug-resistant (MDR) bacterial pathogens is limiting the options for
      effective antibiotic therapy. Moreover, this alarming spread of antimicrobial
      resistance has not been paralleled by the development of novel antimicrobials.
      Resistance to the scarce new antibiotics is also emerging. In this context, the
      rational use of older antibiotics could represent an alternative to the treatment
      of MDR bacterial pathogens. It would help to optimize the armamentarium of
      antibiotics in the way to preserve new antibiotics and avoid the prescription of
      molecules known to favor the spread of resistance (i.e., quinolones).
      Furthermore, in a global economical perspective, this could represent a useful
      public health orientation knowing that several of these cheapest "forgotten"
      antibiotics are not available in many countries. We will review here the
      successful treatment of MDR bacterial infections with the use of old antibiotics
      and discuss their place in current practice. 

PMID- 25368614
TI  - The Story Behind "A Requirement for Two Cell Types for Antibody Formation in
      vitro".

PMID- 25368613
TI  - Crossroads between Bacterial and Mammalian Glycosyltransferases.
AB  - Bacterial glycosyltransferases (GT) often synthesize the same glycan linkages as
      mammalian GT; yet, they usually have very little sequence identity. Nevertheless,
      enzymatic properties, folding, substrate specificities, and catalytic mechanisms
      of these enzyme proteins may have significant similarity. Thus, bacterial GT can
      be utilized for the enzymatic synthesis of both bacterial and mammalian types of
      complex glycan structures. A comparison is made here between mammalian and
      bacterial enzymes that synthesize epitopes found in mammalian glycoproteins, and
      those found in the O antigens of Gram-negative bacteria. These epitopes include
      Thomsen-Friedenreich (TF or T) antigen, blood group O, A, and B, type 1 and 2
      chains, Lewis antigens, sialylated and fucosylated structures, and polysialic
      acids. Many different approaches can be taken to investigate the substrate
      binding and catalytic mechanisms of GT, including crystal structure analyses,
      mutations, comparison of amino acid sequences, NMR, and mass spectrometry.
      Knowledge of the protein structures and functions helps to design GT for specific
      glycan synthesis and to develop inhibitors. The goals are to develop new
      strategies to reduce bacterial virulence and to synthesize vaccines and other
      biologically active glycan structures. 

PMID- 25368612
TI  - Deception and manipulation: the arms of leishmania, a successful parasite.
AB  - Leishmania spp. are intracellular parasitic protozoa responsible for a group of
      neglected tropical diseases, endemic in 98 countries around the world, called
      leishmaniasis. These parasites have a complex digenetic life cycle requiring a
      susceptible vertebrate host and a permissive insect vector, which allow their
      transmission. The clinical manifestations associated with leishmaniasis depend on
      complex interactions between the parasite and the host immune system.
      Consequently, leishmaniasis can be manifested as a self-healing cutaneous
      affliction or a visceral pathology, being the last one fatal in 85-90% of
      untreated cases. As a result of a long host-parasite co-evolutionary process,
      Leishmania spp. developed different immunomodulatory strategies that are
      essential for the establishment of infection. Only through deception and
      manipulation of the immune system, Leishmania spp. can complete its life cycle
      and survive. The understanding of the mechanisms associated with immune evasion
      and disease progression is essential for the development of novel therapies and
      vaccine approaches. Here, we revise how the parasite manipulates cell death and
      immune responses to survive and thrive in the shadow of the immune system. 

PMID- 25368615
TI  - Priming dendritic cells for th2 polarization: lessons learned from helminths and
      implications for metabolic disorders.
AB  - Nearly one quarter of the world's population is infected with helminth parasites.
      A common feature of helminth infections is the manifestation of a type 2 immune
      response, characterized by T helper 2 (Th2) cells that mediate anti-helminth
      immunity. In addition, recent literature describes a close association between
      type 2 immune responses and wound repair, suggesting that a Th2 response may
      concurrently mediate repair of parasite-induced damage. The molecular mechanisms
      that govern Th2 responses are poorly understood, although it is clear that
      dendritic cells (DCs), which are the most efficient antigen-presenting cells in
      the immune system, play a central role. Here, we review the molecular mechanisms
      by which DCs polarize Th2 cells, examining both helminth antigens and helminth
      mediated tissue damage as Th2-inducing triggers. Finally, we discuss the
      implication of these findings in the context of metabolic disorders, as recent
      literature indicates that various aspects of the Th2-associated inflammatory
      response contribute to metabolic homeostasis. 

PMID- 25368616
TI  - Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond.
AB  - Discovery and characterization of the cytokine receptor-cytokine-decoy receptor
      triad formed by receptor activator of nuclear factor kappa-B ligand (RANKL)
      receptor activator of NF-kappaB (RANK)-osteoprotegerin (OPG) have led not only to
      immense advances in understanding the biology of bone homeostasis, but have also
      crystalized appreciation of the critical regulatory relationship that exists
      between bone and immunity, resulting in the emergence of the burgeoning field of
      osteoimmunology. RANKL-RANK-OPG are members of the tumor necrosis factor (TNF)
      and TNF receptor superfamilies, and share signaling characteristics common to
      many members of each. Developmentally regulated and cell-type specific expression
      patterns of each of these factors have revealed key regulatory functions for
      RANKL-RANK-OPG in bone homeostasis, organogenesis, immune tolerance, and cancer.
      Successful efforts at designing and developing therapeutic agents targeting RANKL
      RANK-OPG have been undertaken for osteoporosis, and additional efforts are
      underway for other conditions. In this review, we will summarize the basic
      biology of the RANKL-RANK-OPG system, relate its cell-type specific functions to
      system-wide mechanisms of development and homeostasis, and highlight emerging
      areas of interest for this cytokine group. 

PMID- 25368617
TI  - Small and Long Regulatory RNAs in the Immune System and Immune Diseases.
AB  - Cellular differentiation is regulated on the level of gene expression, and it is
      known that dysregulation of gene expression can lead to deficiencies in
      differentiation that contribute to a variety of diseases, particularly of the
      immune system. Until recently, it was thought that the dysregulation was governed
      by changes in the binding or activity of a class of proteins called transcription
      factors. However, the discovery of micro-RNAs and recent descriptions of long non
      coding RNAs (lncRNAs) have given enormous momentum to a whole new field of
      biology: the regulatory RNAs. In this review, we describe these two classes of
      regulatory RNAs and summarize what is known about how they regulate aspects of
      the adaptive and innate immune systems. Finally, we describe what is known about
      the involvement of micro-RNAs and lncRNAs in three different autoimmune diseases
      (celiac disease, inflammatory bowel disease, and multiple sclerosis). 

PMID- 25368618
TI  - From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation.
AB  - Studies on monocyte and macrophage biology and differentiation have revealed the
      pleiotropic activities of these cells. Macrophages are tissue sentinels that
      maintain tissue integrity by eliminating/repairing damaged cells and matrices. In
      this M2-like mode, they can also promote tumor growth. Conversely, M1-like
      macrophages are key effector cells for the elimination of pathogens, virally
      infected, and cancer cells. Macrophage differentiation from monocytes occurs in
      the tissue in concomitance with the acquisition of a functional phenotype that
      depends on microenvironmental signals, thereby accounting for the many and
      apparently opposed macrophage functions. Many questions arise. When monocytes
      differentiate into macrophages in a tissue (concomitantly adopting a specific
      functional program, M1 or M2), do they all die during the inflammatory reaction,
      or do some of them survive? Do those that survive become quiescent tissue
      macrophages, able to react as naive cells to a new challenge? Or, do monocyte
      derived tissue macrophages conserve a "memory" of their past inflammatory
      activation? This review will address some of these important questions under the
      general framework of the role of monocytes and macrophages in the initiation,
      development, resolution, and chronicization of inflammation. 

PMID- 25368621
TI  - On the Non-Redundant Roles of TDO2 and IDO1.

PMID- 25368620
TI  - Immunological Relevance of the Coevolution of IDO1 and AHR.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      initially identified because of its role in controlling the cellular response to
      environmental molecules. More recently, AHR has been shown to play a crucial role
      in controlling innate and adaptive immune responses through several mechanisms,
      one of which is the regulation of tryptophan metabolism. Indoleamine-2,3
      dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are considered rate
      limiting enzymes in the tryptophan catabolism and play important roles in the
      regulation of the immunity. Moreover, AHR and IDO/TDO are closely interconnected:
      AHR regulates IDO and TDO expression, and kynurenine produced by IDO/TDO is an
      AHR agonist. In this review, we propose to examine the relationship between AHR
      and IDO/TDO and its relevance for the regulation of the immune response in health
      and disease. 

PMID- 25368619
TI  - IgG subclasses and allotypes: from structure to effector functions.
AB  - Of the five immunoglobulin isotypes, immunoglobulin G (IgG) is most abundant in
      human serum. The four subclasses, IgG1, IgG2, IgG3, and IgG4, which are highly
      conserved, differ in their constant region, particularly in their hinges and
      upper CH2 domains. These regions are involved in binding to both IgG-Fc receptors
      (FcgammaR) and C1q. As a result, the different subclasses have different effector
      functions, both in terms of triggering FcgammaR-expressing cells, resulting in
      phagocytosis or antibody-dependent cell-mediated cytotoxicity, and activating
      complement. The Fc-regions also contain a binding epitope for the neonatal Fc
      receptor (FcRn), responsible for the extended half-life, placental transport, and
      bidirectional transport of IgG to mucosal surfaces. However, FcRn is also
      expressed in myeloid cells, where it participates in both phagocytosis and
      antigen presentation together with classical FcgammaR and complement. How these
      properties, IgG-polymorphisms and post-translational modification of the
      antibodies in the form of glycosylation, affect IgG-function will be the focus of
      the current review. 

PMID- 25368622
TI  - Sustained mitogen-activated protein kinase activation reprograms defense
      metabolism and phosphoprotein profile in Arabidopsis thaliana.
AB  - Mitogen-activated protein kinases (MAPKs) target a variety of protein substrates
      to regulate cellular signaling processes in eukaryotes. In plants, the number of
      identified MAPK substrates that control plant defense responses is still limited.
      Here, we generated transgenic Arabidopsis thaliana plants with an inducible
      system to simulate in vivo activation of two stress-activated MAPKs, MPK3, and
      MPK6. Metabolome analysis revealed that this artificial MPK3/6 activation
      (without any exposure to pathogens or other stresses) is sufficient to drive the
      production of major defense-related metabolites, including various camalexin,
      indole glucosinolate and agmatine derivatives. An accompanying (phospho)proteome
      analysis led to detection of hundreds of potential phosphoproteins downstream of
      MPK3/6 activation. Besides known MAPK substrates, many candidates on this list
      possess typical MAPK-targeted phosphosites and in many cases, the corresponding
      phosphopeptides were detected by mass spectrometry. Notably, several of these
      putative phosphoproteins have been reported to be associated with the
      biosynthesis of antimicrobial defense substances (e.g., WRKY transcription
      factors and proteins encoded by the genes from the "PEN" pathway required for
      penetration resistance to filamentous pathogens). Thus, this work provides an
      inventory of candidate phosphoproteins, including putative direct MAPK
      substrates, for future analysis of MAPK-mediated defense control. (Proteomics
      data are available with the identifier PXD001252 via ProteomeXchange,
      http://proteomecentral.proteomexchange.org). 

PMID- 25368623
TI  - Gel-free proteomic analysis of soybean root proteins affected by calcium under
      flooding stress.
AB  - Soybean is sensitive to flooding stress and exhibits reduced growth under
      flooding conditions. To better understand the flooding-responsive mechanisms of
      soybean, the effect of exogenous calcium on flooding-stressed soybeans was
      analyzed using proteomic technique. An increase in exogenous calcium levels
      enhanced soybean root elongation and suppressed the cell death of root tip under
      flooding stress. Proteins were extracted from the roots of 4-day-old soybean
      seedlings exposed to flooding stress without or with calcium for 2 days and
      analyzed using gel-free proteomic technique. Proteins involved in protein
      degradation/synthesis/posttranslational modification, hormone/cell wall
      metabolisms, and DNA synthesis were decreased by flooding stress; however, their
      reductions were recovered by calcium treatment. Development, lipid metabolism,
      and signaling-related proteins were increased in soybean roots when calcium was
      supplied under flooding stress. Fermentation and glycolysis-related proteins were
      increased in response to flooding; however, these proteins were not affected by
      calcium supplementation. Furthermore, urease and copper chaperone proteins
      exhibited similar profiles in 4-day-old untreated soybeans and 4-day-old soybeans
      exposed to flooding for 2 days in the presence of calcium. These results suggest
      that calcium might affect the cell wall/hormone metabolisms, protein
      degradation/synthesis, and DNA synthesis in soybean roots under flooding stress. 

PMID- 25368624
TI  - The non-homologous end-joining pathway is involved in stable transformation in
      rice.
AB  - Stable transformation with T-DNA needs the coordinated activities of many
      proteins derived from both host plant cells and Agrobacterium. In dicot plants,
      including Arabidopsis, it has been suggested that non-homologous end-joining
      (NHEJ)-one of the main DNA double-strand break repair pathways-is involved in the
      T-DNA integration step that is crucial to stable transformation. However, how
      this pathway is involved remains unclear as results with NHEJ mutants in
      Arabidopsis have given inconsistent results. Recently, a system for visualization
      of stable expression of genes located on T-DNA has been established in rice
      callus. Stable expression was shown to be reduced significantly in NHEJ knock
      down rice calli, suggesting strongly that NHEJ is involved in Agrobacterium
      mediated stable transformation in rice. Since rice transformation is now
      efficient and reproducible, rice is a good model plant in which to elucidate the
      molecular mechanisms of T-DNA integration. 

PMID- 25368625
TI  - Expression, regulation and activity of a B2-type cyclin in mitotic and
      endoreduplicating maize endosperm.
AB  - Cyclin-dependent kinases, the master regulators of the eukaryotic cell cycle, are
      complexes comprised of a catalytic serine/threonine protein kinase and an
      essential regulatory cyclin. The maize genome encodes over 50 cyclins grouped in
      different types, but they have been little investigated. We characterized a type
      B2 cyclin (CYCB2;2) during maize endosperm development, which comprises a cell
      proliferation phase based on the standard mitotic cell cycle, followed by an
      endoreduplication phase in which DNA replication is reiterated in the absence of
      mitosis or cytokinesis. CYCB2;2 RNA was present throughout the period of
      endosperm development studied, but its level declined as the endosperm
      transitioned from a mitotic to an endoreduplication cell cycle. However, the
      level of CYCB2;2 protein remained relatively constant during both stages of
      endosperm development. CYCB2;2 was recalcitrant to degradation by the 26S
      proteasome in endoreduplicating endosperm extracts, which could explain its
      sustained accumulation during endosperm development. In addition, although
      CYCB2;2 was generally localized to the nucleus of endosperm cells, a lower
      molecular weight form of the protein accumulated specifically in the cytosol of
      endoreduplicating endosperm cells. In dividing cells, CYCB2;2 appeared to be
      localized to the phragmoplast and may be involved in cytokinesis and cell wall
      formation. Kinase activity was associated with CYCB2;2 in mitotic endosperm, but
      was absent or greatly reduced in immature ear and endoreduplicating endosperm.
      CYCB2;2-associated kinase phosphorylated maize E2F1 and the "pocket" domains of
      RBR1 and RBR3. CYCB2;2 interacted with both maize CDKA;1 and CDKA;3 in insect
      cells. These results suggest CYCB2;2 functions primarily during the mitotic cell
      cycle, and they are discussed in the context of the roles of cyclins, CDKs and
      proteasome activity in the regulation of the cell cycle during endosperm
      development. 

PMID- 25368626
TI  - Arbuscular mycorrhizal symbiosis and osmotic adjustment in response to NaCl
      stress: a meta-analysis.
AB  - Arbuscular mycorrhizal (AM) symbiosis can enhance plant resistance to NaCl stress
      in several ways. Two fundamental roles involve osmotic and ionic adjustment. By
      stimulating accumulation of solutes, the symbiosis can help plants sustain
      optimal water balance and diminish Na(+) toxicity. The size of the AM effect on
      osmolytes has varied widely and is unpredictable. We conducted a meta-analysis to
      determine the size of the AM effect on 22 plant solute characteristics after
      exposure to NaCl and to examine how experimental conditions have influenced the
      AM effect. Viewed across studies, AM symbioses have had marked effects on plant
      K(+), increasing root and shoot K(+) concentrations by an average of 47 and 42%,
      respectively, and root and shoot K(+)/Na(+) ratios by 47 and 58%, respectively.
      Among organic solutes, soluble carbohydrates have been most impacted, with AM
      induced increases of 28 and 19% in shoots and roots. The symbiosis has had no
      consistent effect on several characteristics, including root glycine betaine
      concentration, root or shoot Cl(-) concentrations, leaf Psipi, or shoot proline
      or polyamine concentrations. The AM effect has been very small for shoot Ca(++)
      concentration and root concentrations of Na(+), Mg(++) and proline.
      Interpretations about AM-conferred benefits regarding these compounds may be best
      gauged within the context of the individual studies. Shoot and root K(+)/Na(+)
      ratios and root proline concentration showed significant between-study
      heterogeneity, and we examined nine moderator variables to explore what might
      explain the differences in mycorrhizal effects on these parameters. Moderators
      with significant impacts included AM taxa, host type, presence or absence of AM
      growth promotion, stress severity, and whether NaCl constituted part or all of
      the experimental saline stress treatment. Meta-regression of shoot K(+)/Na(+)
      ratio showed a positive response to root colonization, and root K(+)/Na(+) ratio
      a negative response to time of exposure to NaCl. 

PMID- 25368628
TI  - Using multi-locus allelic sequence data to estimate genetic divergence among four
      Lilium (Liliaceae) cultivars.
AB  - Next Generation Sequencing (NGS) may enable estimating relationships among
      genotypes using allelic variation of multiple nuclear genes simultaneously. We
      explored the potential and caveats of this strategy in four genetically distant
      Lilium cultivars to estimate their genetic divergence from transcriptome
      sequences using three approaches: POFAD (Phylogeny of Organisms from Allelic
      Data, uses allelic information of sequence data), RAxML (Randomized Accelerated
      Maximum Likelihood, tree building based on concatenated consensus sequences) and
      Consensus Network (constructing a network summarizing among gene tree conflicts).
      Twenty six gene contigs were chosen based on the presence of orthologous
      sequences in all cultivars, seven of which also had an orthologous sequence in
      Tulipa, used as out-group. The three approaches generated the same topology.
      Although the resolution offered by these approaches is high, in this case there
      was no extra benefit in using allelic information. We conclude that these 26
      genes can be widely applied to construct a species tree for the genus Lilium. 

PMID- 25368627
TI  - Compartment-specific importance of glutathione during abiotic and biotic stress.
AB  - The tripeptide thiol glutathione (gamma-L-glutamyl-L-cysteinyl-glycine) is the
      most important sulfur containing antioxidant in plants and essential for plant
      defense against abiotic and biotic stress conditions. It is involved in the
      detoxification of reactive oxygen species (ROS), redox signaling, the modulation
      of defense gene expression, and the regulation of enzymatic activities. Even
      though changes in glutathione contents are well documented in plants and its
      roles in plant defense are well established, still too little is known about its
      compartment-specific importance during abiotic and biotic stress conditions. Due
      to technical advances in the visualization of glutathione and the redox state
      through microscopical methods some progress was made in the last few years in
      studying the importance of subcellular glutathione contents during stress
      conditions in plants. This review summarizes the data available on compartment
      specific importance of glutathione in the protection against abiotic and biotic
      stress conditions such as high light stress, exposure to cadmium, drought, and
      pathogen attack (Pseudomonas, Botrytis, tobacco mosaic virus). The data will be
      discussed in connection with the subcellular accumulation of ROS during these
      conditions and glutathione synthesis which are both highly compartment specific
      (e.g., glutathione synthesis takes place in chloroplasts and the cytosol). Thus
      this review will reveal the compartment-specific importance of glutathione during
      abiotic and biotic stress conditions. 

PMID- 25368629
TI  - A 2-step strategy for detecting pleiotropic effects on multiple longitudinal
      traits.
AB  - Genetic pleiotropy refers to the situation in which a single gene influences
      multiple traits and so it is considered as a major factor that underlies genetic
      correlation among traits. To identify pleiotropy, an important focus in genome
      wide association studies (GWAS) is on finding genetic variants that are
      simultaneously associated with multiple traits. On the other hand, longitudinal
      designs are often employed in many complex disease studies, such that, traits are
      measured repeatedly over time within the same subject. Performing genetic
      association analysis simultaneously on multiple longitudinal traits for detecting
      pleiotropic effects is interesting but challenging. In this paper, we propose a 2
      step method for simultaneously testing the genetic association with multiple
      longitudinal traits. In the first step, a mixed effects model is used to analyze
      each longitudinal trait. We focus on estimation of the random effect that
      accounts for the subject-specific genetic contribution to the trait; fixed
      effects of other confounding covariates are also estimated. This first step
      enables separation of the genetic effect from other confounding effects for each
      subject and for each longitudinal trait. Then in the second step, we perform a
      simultaneous association test on multiple estimated random effects arising from
      multiple longitudinal traits. The proposed method can efficiently detect
      pleiotropic effects on multiple longitudinal traits and can flexibly handle
      traits of different data types such as quantitative, binary, or count data. We
      apply this method to analyze the 16th Genetic Analysis Workshop (GAW16)
      Framingham Heart Study (FHS) data. A simulation study is also conducted to
      validate this 2-step method and evaluate its performance. 

PMID- 25368630
TI  - Controlling variation in the comet assay.
AB  - Variability of the comet assay is a serious issue, whether it occurs from
      experiment to experiment in the same laboratory, or between different
      laboratories analysing identical samples. Do we have to live with high
      variability, just because the comet assay is a biological assay rather than
      analytical chemistry? Numerous attempts have been made to limit variability by
      standardizing the assay protocol, and the critical steps in the assay have been
      identified; agarose concentration, duration of alkaline incubation, and
      electrophoresis conditions (time, temperature, and voltage gradient) are
      particularly important. Even when these are controlled, variation seems to be
      inevitable. It is helpful to include in experiments reference standards, i.e.,
      cells with a known amount of specific damage to the DNA. They can be aliquots
      frozen from a single large batch of cells, either untreated (negative controls)
      or treated with, for example, H2O2 or X-rays to induce strand breaks (positive
      control for the basic assay), or photosensitiser plus light to oxidize guanine
      (positive control for Fpg- or OGG1-sensitive sites). Reference standards are
      especially valuable when performing a series of experiments over a long period
      for example, analysing samples of white blood cells from a large human
      biomonitoring trial-to check that the assay is performing consistently, and to
      identify anomalous results necessitating a repeat experiment. The reference
      values of tail intensity can also be used to iron out small variations occurring
      from day to day. We present examples of the use of reference standards in human
      trials, both within one laboratory and between different laboratories, and
      describe procedures that can be used to control variation. 

PMID- 25368631
TI  - New observations in the fragile X-associated tremor/ataxia syndrome (FXTAS)
      phenotype.
AB  - PURPOSE: Fragile X-associated tremor/ataxia syndrome (FXTAS) was originally
      defined as tremor, ataxia, cognitive decline, and parkinsonism in individuals who
      carry between 55 and 200 CGG repeats in the promoter region of the fragile X
      mental retardation 1 (FMR1) gene. This paper describes a series of patients who
      meet the definition of FXTAS who presented for care between 2009 and 2014.
      METHODS/RESULTS: Retrospective chart review of patients seen in the FXTAS clinic
      at Rush University in Chicago. CONCLUSIONS: Patients with FXTAS may present with
      a progressive supranuclear palsy-like phenotype and other eye movement
      abnormalities are common in these patients as well. Rapid worsening of gait
      abnormalities in FXTAS may be due to a secondary spinal issue and should be
      aggressively treated to regain function. Finally, the FXTAS Rating Scale score
      does not reliably inform the certainty of diagnosis or CGG repeat size in these
      patients.

PMID- 25368632
TI  - Antioxidant effects of the orientin and vitexin in Trollius chinensis Bunge in D
      galactose-aged mice.
AB  - Total flavonoids are the main pharmaceutical components of Trollius chinensis
      Bunge, and orientin and vitexin are the monomer components of total flavonoids in
      Trollius chinensis Bunge. In this study, an aged mouse model was established
      through intraperitoneal injection of D-galactose for 8 weeks, followed by
      treatment with 40, 20, or 10 mg/kg orientin, vitexin, or a positive control
      (vitamin E) via intragastric administration for an additional 8 weeks. Orientin,
      vitexin, and vitamin E improved the general medical status of the aging mice and
      significantly increased their brain weights. They also produced an obvious rise
      in total antioxidant capacity, superoxide dismutase, catalase, and glutathione
      peroxidase levels in the serum, and the levels of superoxide dismutase, catalase
      and glutathione peroxidase, Na(+)-K(+)-ATP enzyme, and Ca(2+)-Mg(2+)-ATP enzyme
      in the liver, brain and kidneys. In addition, they significantly reduced
      malondialdehyde levels in the liver, brain and kidney and lipofuscin levels in
      the brain. They also significantly improved the neuronal ultrastructure. The 40
      mg/kg dose of orientin and vitexin had the same antioxidant capacity as vitamin
      E. These experimental findings indicate that orientin and vitexin engender anti
      aging effects through their antioxidant capacities. 

PMID- 25368633
TI  - Underlying mechanism of protection from hypoxic injury seen with n-butanol
      extract of Potentilla anserine L. in hippocampal neurons.
AB  - The alcohol and n-butanol extract of Potentilla anserine L. significantly
      protects myocardium from acute ischemic injury. However, its effects on rat
      hippocampal neurons and the mechanism of protection remain unclear. In this
      study, primary cultured hippocampal neurons from neonatal rats were incubated in
      95% N2 and 5% CO2 for 4 hours. Results indicated that hypoxic injury decreased
      the viability of neurons, increased the expression levels of caspase-9 and
      caspase-3 mRNA, as well as cytochrome c, Caspase-9, and Caspase-3 protein.
      Pretreatment with 0.25, 0.062 5, 0.015 6 mg/mL n-butanol extract of Potentilla
      anserine L. led to a significant increase in cell viability. Expression levels of
      caspase-9 and caspase-3 mRNA, as well as cytochrome c, Caspase-9, and Caspase-3
      protein, were attenuated. The neuroprotective effect of n-butanol extract of
      Potentilla anserine L. was equivalent to tanshinone IIA. Our data suggest that
      the n-butanol extract of Potentilla anserine L. could protect primary hippocampal
      neurons from hypoxic injury by deactivating mitochondrial cell death. 

PMID- 25368634
TI  - Puerarin prevents high glucose-induced apoptosis of Schwann cells by inhibiting
      oxidative stress.
AB  - Oxidative stress may be the unifying factor for the injury caused by
      hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major
      isoflavonoid derived from Radix puerariae and has been shown to be effective in
      increasing superoxide dismutase activity. This study sought to investigate the
      neuroprotective effect of puerarin on high glucose-induced oxidative stress and
      Schwann cell apoptosis in vitro. Intracellular reactive oxygen radicals and
      mitochondrial transmembrane potential were detected by flow cytometry analysis.
      Apoptosis was confirmed by TUNEL and oxidative stress was monitored using an
      enzyme-linked immunosorbent assay for the DNA marker 8-hydroxy-2-deoxyguanosine.
      The expression levels of bax and bcl-2 were analyzed by quantitative real-time
      reverse transcriptase-PCR, while protein expression of cleaved caspase-3 and -9
      were analyzed by means of western blotting. Results suggested that puerarin
      treatment inhibited high glucose-induced oxidative stress, mitochondrial
      depolarization and apoptosis in a dose-dependent manner. Furthermore, puerarin
      treatment downregulated Bax expression, upregulated bcl-2 expression and
      attenuated the activation of caspase-3 and -9. Overall, our results indicated
      that puerarin antagonized high glucose-induced oxidative stress and apoptosis in
      Schwann cells. 

PMID- 25368635
TI  - Shuanghuanglian injection downregulates nuclear factor-kappa B expression in mice
      with viral encephalitis.
AB  - A mouse model of viral encephalitis was induced by intracranial injection of a
      Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR
      and western blot assay were applied to detect mRNA and protein expression of
      intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control
      groups. Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were
      significantly increased in mice with viral encephalitis. After intraperitoneal
      injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days,
      intelectin-2 and nuclear factor-kappa B protein and mRNA expression were
      significantly decreased. To elucidate the relationship between intelectin-2 and
      nuclear factor-kappa B, mice with viral encephalitis were administered an
      intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin
      shRNA. Both protein and mRNA levels of intelectin and nuclear factor-kappa B in
      brain tissue of mice were significantly decreased. Experimental findings suggest
      that Shuanghuanglian injection may downregulate nuclear factor-kappa B production
      via suppression of intelectin production, thus inhibiting inflammation associated
      with viral encephalitis. 

PMID- 25368636
TI  - Heat-sensitive moxibustion attenuates the inflammation after focal cerebral
      ischemia/ reperfusion injury.
AB  - Heat-sensitive moxibustion has neuroprotective effects against focal cerebral
      ischemia/reperfusion injury, however its mechanism of action remains unclear. In
      this study, rat models of focal cerebral ischemia/reperfusion injury were treated
      with suspended moxibustion at acupoint Dazhui (DU14) for 35 minutes. Results
      showed that suspended moxibustion decreased infarct volume, reduced cortical
      myeloperoxidase activity, and suppressed serum levels of proinflammatory
      cytokines in rats with focal cerebral ischemia/reperfusion injury. Our
      experimental findings indicated that heat-sensitive moxibustion can attenuate
      inflammation and promote repair after focal cerebral ischemia/reperfusion injury.

PMID- 25368637
TI  - Acupuncture inhibits cue-induced heroin craving and brain activation.
AB  - Previous research using functional MRI has shown that specific brain regions
      associated with drug dependence and cue-elicited heroin craving are activated by
      environmental cues. Craving is an important trigger of heroin relapse, and
      acupuncture may inhibit craving. In this study, we performed functional MRI in
      heroin addicts and control subjects. We compared differences in brain activation
      between the two groups during heroin cue exposure, heroin cue exposure plus
      acupuncture at the Zusanli point (ST36) without twirling of the needle, and
      heroin cue exposure plus acupuncture at the Zusanli point with twirling of the
      needle. Heroin cue exposure elicited significant activation in craving-related
      brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without
      twirling did not significantly affect the range of brain activation induced by
      heroin cue exposure, but significantly changed the extent of the activation in
      the heroin addicts group. Acupuncture at the Zusanli point with twirling of the
      needle significantly decreased both the range and extent of activation induced by
      heroin cue exposure compared with heroin cue exposure plus acupuncture without
      twirling of the needle. These experimental findings indicate that presentation of
      heroin cues can induce activation in craving-related brain regions, which are
      involved in reward, learning and memory, cognition and emotion. Acupuncture at
      the Zusanli point can rapidly suppress the activation of specific brain regions
      related to craving, supporting its potential as an intervention for drug craving.

PMID- 25368638
TI  - Electroacupuncture improves neuropathic pain: Adenosine, adenosine 5'
      triphosphate disodium and their receptors perhaps change simultaneously.
AB  - Applying a stimulating current to acupoints through acupuncture needles - known
      as electroacupuncture - has the potential to produce analgesic effects in human
      subjects and experimental animals. When acupuncture was applied in a rat model,
      adenosine 5'-triphosphate disodium in the extracellular space was broken down
      into adenosine, which in turn inhibited pain transmission by means of an
      adenosine A1 receptor-dependent process. Direct injection of an adenosine A1
      receptor agonist enhanced the analgesic effect of acupuncture. The analgesic
      effect of acupuncture appears to be mediated by activation of A1 receptors
      located on ascending nerves. In neuropathic pain, there is upregulation of P2X
      purinoceptor 3 (P2X3) receptor expression in dorsal root ganglion neurons.
      Conversely, the onset of mechanical hyperalgesia was diminished and established
      hyperalgesia was significantly reversed when P2X3 receptor expression was
      downregulated. The pathways upon which electroacupuncture appear to act are
      interwoven with pain pathways, and electroacupuncture stimuli converge with
      impulses originating from painful areas. Electroacupuncture may act via
      purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on
      neuropathic pain. 

PMID- 25368639
TI  - Use of stem cell transplantation to treat epilepsy: A Web of Science-based
      literature analysis.
AB  - OBJECTIVE: To identify global research trends in the use of stem cell
      transplantation to treat epilepsy. DATA RETRIEVAL: We performed a bibliometric
      analysis of studies on the use of stem cell transplantation to treat epilepsy
      during 2002-2011, retrieved from Web of Science, using the key words epilepsy or
      epileptic or epilepticus or seizure and "stem cell". SELECTION CRITERIA: 
      INCLUSION CRITERIA: (a) peer-reviewed published articles on the use of stem cell
      transplantation to treat epilepsy indexed in Web of Science; (b) original
      research articles, reviews, meeting abstracts, proceedings papers, book chapters,
      editorial material, and news items. MAIN OUTCOME MEASURES: (a) Annual publication
      output; (b) type of publication; (c) publication by research field; (d)
      publication by journal; (e) publication by author; (f) publication by country and
      institution; (g) publications by institution in China; (h) most-cited papers; and
      (i) papers published by Chinese authors or institutions. RESULTS: A total of 460
      publications on the use of stem cell transplantation to treat epilepsy were
      retrieved from Web of Science, 2002-2011. The number of publications gradually
      increased over the 10-year study period. Articles and reviews constituted the
      major types of publications. More than half of the studies were in the field of
      neuroscience/neurology. The most prolific journals for this topic were Epilepsia,
      Bone Marrow Transplantation, and Journal of Neuroscience. Of the 460
      publications, almost half came from American authors and institutions; relatively
      few papers were published by Chinese authors or institutions. CONCLUSION:
      Literature on stem cell transplantation for epilepsy includes many reports of
      basic research, but few of clinical trials or treatments. Exact effects are not
      yet evaluated. Epilepsy rehabilitation is a long-term, complex, and comprehensive
      system engineering. With advances in medical development, some effective medical,
      social and educational measures are needed to facilitate patient's treatment and
      training and accelerate the recovery of life ability, learning ability and social
      adaptability to the largest extent to improve patient's quality of life.

PMID- 25368640
TI  - Therapies for children with cerebral palsy: A Web of Science-based literature
      analysis.
AB  - OBJECTIVE: To identify global research trends in three therapies for children
      with cerebral palsy. DATA RETRIEVAL: We performed a bibliometric analysis of
      studies on therapies for children with cerebral palsy from 2002 to 2011 retrieved
      from Web of Science. SELECTION CRITERIA:  INCLUSION CRITERIA: (a) peer-reviewed
      published articles on botulinum toxin, constraint-induced movement therapy, or
      acupuncture for children with cerebral palsy indexed in Web of Science; (b)
      original research articles, reviews, meeting abstracts, proceedings papers, book
      chapters, editorial material, and news items; and (c) publication between 2002
      and 2011. EXCLUSION CRITERIA: (a) articles that required manual searching or
      telephone access; (b) documents that were not published in the public domain; and
      (c) a number of corrected papers from the total number of articles. MAIN OUTCOME
      MEASURES: (1) Number of publications on the three therapies; (2) annual
      publication output, distribution by journals, distribution by institution, and
      top-cited articles on botulinum toxin; (3) annual publication output,
      distribution by journal, distribution by institution, and top-cited articles on
      constraint-induced movement therapy; (4) annual publication, distribution by
      journal, distribution by institution, and top-cited articles on acupuncture.
      RESULTS: This analysis, based on Web of Science articles, identified several
      research trends in studies published over the past 10 years of three therapies
      for children with cerebral palsy. More articles on botulinum toxin for treating
      children with cerebral palsy were published than the articles regarding
      constraint-induced movement therapy or acupuncture. The numbers of publications
      increased over the 10-year study period. Most papers appeared in journals with a
      focus on neurology, such as Developmental Medicine and Child Neurology and
      Journal of Child Neurology. Research institutes publishing on botulinum toxin
      treatments for this population are mostly in the Netherlands, the United States
      of America, and Australia; those publishing on constraint-induced movement
      therapy are mostly in Australia and the United States of America; and those
      publishing on acupuncture are mostly in China, Sweden and the United States of
      America. CONCLUSION: Analysis of literature and research trends indicated that
      there was no one specific therapy to cure cerebral palsy. Further studies are
      still necessary.

PMID- 25368641
TI  - Extracellular matrices, artificial neural scaffolds and the promise of neural
      regeneration.
AB  - Over last 20 years, extracellular matrices have been shown to be useful in
      promoting tissue regeneration. Recently, they have been used and have had success
      in achieving neurogenesis. Recent developments in extracellular matrix design
      have allowed their successful in vivo incorporation to engender an environment
      favorable for neural regeneration in animal models. Promising treatments under
      investigation include manipulation of the intrinsic extracellular matrix and
      incorporation of engineered naometer-sized scaffolds through which inhibition of
      molecules serving as barriers to neuroregeneration and delivery of neurotrophic
      factors and/or cells for successful tissue regeneration can be achieved. Further
      understanding of the changes incurred within the extracellular matrix following
      central nervous system injury will undoubtedly help design a clinically
      efficacious extracellular matrix scaffold that can mitigate or reverse neural
      degeneration in the clinical setting. 

PMID- 25368642
TI  - Selective CDK inhibitors: promising candidates for future clinical traumatic
      brain injury trials.
AB  - Traumatic brain injury induces secondary injury that contributes to
      neuroinflammation, neuronal loss, and neurological dysfunction. One important
      injury mechanism is cell cycle activation which causes neuronal apoptosis and
      glial activation. The neuroprotective effects of both non-selective
      (Flavopiridol) and selective (Roscovitine and CR-8) cyclin-dependent kinase
      inhibitors have been shown across multiple experimental traumatic brain injury
      models and species. Cyclin-dependent kinaseinhibitors, administered as a single
      systemic dose up to 24 hours after traumatic brain injury, provide strong
      neuroprotection-reducing neuronal cell death, neuroinflammation and neurological
      dysfunction. Given their effectiveness and long therapeutic window, cyclin
      dependent kinase inhibitors appear to be promising candidates for clinical
      traumatic brain injury trials. 

PMID- 25368643
TI  - Induction of ischemic tolerance as a promising treatment against diabetic
      retinopathy.
AB  - Diabetic retinopathy is a leading cause of acquired blindness, and it is the most
      common ischemic disorder of the retina. Available treatments are not very
      effective. Efforts to inhibit diabetic retinopathy have focused either on highly
      specific therapeutic approaches for pharmacologic targets or using genetic
      approaches to change expression of certain enzymes. However, it might be wise to
      choose innovative treatment modalities that act by multiple potential mechanisms.
      The resistance to ischemic injury, or ischemic tolerance, can be transiently
      induced by prior exposure to a non-injurious preconditioning stimulus. A complete
      functional and histologic protection against retinal ischemic damage can be
      achieved by previous preconditioning with non-damaging ischemia. In this review,
      we will discuss evidence that supports that ischemic conditioning could help
      avert the dreaded consequences that results from retinal diabetic damage. 

PMID- 25368644
TI  - Neuroprotective effects of vagus nerve stimulation on traumatic brain injury.
AB  - Previous studies have shown that vagus nerve stimulation can improve the
      prognosis of traumatic brain injury. The aim of this study was to elucidate the
      mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits
      with brain explosive injury. Rabbits with brain explosive injury received
      continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus
      nerve. Tumor necrosis factor-alpha, interleukin-1beta and interleukin-10
      concentrations were detected in serum and brain tissues, and water content in
      brain tissues was measured. Results showed that vagus nerve stimulation could
      reduce the degree of brain edema, decrease tumor necrosis factor-alpha and
      interleukin-1beta concentrations, and increase interleukin-10 concentration after
      brain explosive injury in rabbits. These data suggest that vagus nerve
      stimulation may exert neuroprotective effects against explosive injury via
      regulating the expression of tumor necrosis factor-alpha, interleukin-1beta and
      interleukin-10 in the serum and brain tissue. 

PMID- 25368645
TI  - Mechanisms underlying attenuation of apoptosis of cortical neurons in the hypoxic
      brain by flavonoids from the stems and leaves of Scutellaria baicalensis Georgi.
AB  - Flavonoids from the stems and leaves of Scutellaria baicalensis Georgi, an
      antioxidant, markedly improve memory impairments and neuronal injuries. In the
      present study, primary cortical neurons of rats were exposed to potassium cyanide
      to establish a model of in vitro neural cell apoptosis. Inhibition of apoptosis
      by flavonoids from the stems and leaves of Scutellaria baicalensis Georgi at
      concentrations of 18.98, 37.36, and 75.92 MUg/mL was detected using this model.
      These flavonoids dramatically increased cell survival, inhibited cell apoptosis
      and excessive production of malondialdehyde, and increased the activities of
      superoxide dismutase, glutathione peroxidase, and Na(+)-K(+)-ATPase in primary
      cortical neurons exposed to potassium cyanide. The flavonoids from the stems and
      leaves of Scutellaria baicalensis Georgi were originally found to have a
      polyhydric structure and to protect against cerebral hypoxia in in vitro and in
      vivo models, including hypoxia induced by potassium cyanide or cerebral ischemia.
      The present study suggests that flavonoids from the stems and leaves of
      Scutellaria baicalensis Georgi exert neuroprotective effects via modulation of
      oxidative stress, such as malondialdehyde, superoxide dismutase, glutathione
      peroxidase and Na(+)-K(+)-ATPase disorders induced by potassium cyanide. 

PMID- 25368646
TI  - Autophagy occurs within an hour of adenosine triphosphate treatment after nerve
      cell damage: the neuroprotective effects of adenosine triphosphate against
      apoptosis.
AB  - After hypoxia, ischemia, or inflammatory injuries to the central nervous system,
      the damaged cells release a large amount of adenosine triphosphate, which may
      cause secondary neuronal death. Autophagy is a form of cell death that also has
      neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining,
      flow cytometry, western blotting, and real-time PCR were used to determine the
      effects of exogenous adenosine triphosphate treatment at different concentrations
      (2, 4, 6, 8, 10 mmol/L) over time (1, 2, 3, and 6 hours) on the apoptosis and
      autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine
      triphosphate induced autophagy and apoptosis of SH-SY5Y cells. The enhanced
      autophagy first appeared, and peaked at 1 hour after treatment with adenosine
      triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours.
      With prolonged exposure to the adenosine triphosphate treatment, the fraction of
      apoptotic cells increased. These data suggest that the SH-SY5Y neural cells
      initiated autophagy against apoptosis within an hour of adenosine triphosphate
      treatment to protect themselves against injury. 

PMID- 25368647
TI  - Tooth loss inhibits neurogenesis in the dentate gyrus of adult mice.
AB  - Tooth loss has been shown to affect learning and memory in mice and increases the
      risk of Alzheimer's disease. The dentate gyrus is strongly associated with
      cognitive function. This study hypothesized that tooth loss affects neurons in
      the dentate gyrus. Adult male mice were randomly assigned to either the tooth
      loss group or normal control group. In the tooth loss group, the left maxillary
      and mandibular molars were extracted. Normal control mice did not receive any
      intervention. Immunofluorescence staining revealed that the density and
      absorbance of doublecortin- and neuronal nuclear antigen-positive cells were
      lower in the tooth loss group than in the normal control group. These data
      suggest that tooth loss may inhibit neurogenesis in the dentate gyrus of adult
      mice. 

PMID- 25368648
TI  - Damage of hippocampal neurons in rats with chronic alcoholism.
AB  - Chronic alcoholism can damage the cytoskeleton and aggravate neurological
      deficits. However, the effect of chronic alcoholism on hippocampal neurons
      remains unclear. In this study, a model of chronic alcoholism was established in
      rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide
      content and cystathionine-beta-synthase activity in the hippocampus of rats with
      chronic alcoholism were significantly increased, while F-actin expression was
      decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a
      fuzzy nuclear membrane, mitochondrial edema, and ruptured mitochondrial crista.
      These findings suggest that chronic alcoholism can cause learning and memory
      decline in rats, which may be associated with the hydrogen sulfide/cystathionine
      beta-synthase system, mitochondrial damage and reduced expression of F-actin. 

PMID- 25368649
TI  - Methylmercury chloride damage to the adult rat hippocampus cannot be detected by
      proton magnetic resonance spectroscopy.
AB  - Previous studies have found that methylmercury can damage hippocampal neurons and
      accordingly cause cognitive dysfunction. However, a non-invasive, safe and
      accurate detection method for detecting hippocampal injury has yet to be
      developed. This study aimed to detect methylmercury-induced damage on hippocampal
      tissue using proton magnetic resonance spectroscopy. Rats were given a
      subcutaneous injection of 4 and 2 mg/kg methylmercury into the neck for 50
      consecutive days. Water maze and pathology tests confirmed that cognitive
      function had been impaired and that the ultrastructure of hippocampal tissue was
      altered after injection. The results of proton magnetic resonance spectroscopy
      revealed that the nitrogen-acetyl aspartate/creatine, choline complex/creatine
      and myoinositol/creatine ratio in rat hippocampal tissue were unchanged.
      Therefore, proton magnetic resonance spectroscopy can not be used to determine
      structural damage in the adult rat hippocampus caused by methylmercury chloride. 

PMID- 25368650
TI  - Neuroprotective effects of Buyang Huanwu decoction on cerebral ischemia-induced
      neuronal damage.
AB  - Among the various treatment methods for stroke, increasing attention has been
      paid to traditional Chinese medicines. Buyang Huanwu decoction is a commonly used
      traditional Chinese medicine for the treatment of stroke. This paper summarizes
      the active components of the Chinese herb, which is composed of Huangqi (Radix
      Astragali seu Hedysari), Danggui (Radix Angelica sinensis), Chishao (Radix
      Paeoniae Rubra), Chuanxiong (Rhizoma Ligustici Chuanxiong), Honghua (Flos
      Carthami), Taoren (Semen Persicae) and Dilong (Pheretima), and identifies the
      therapeutic targets and underlying mechanisms that contribute to the
      neuroprotective properties of Buyang Huanwu decoction. 

PMID- 25368651
TI  - Virtual reality training improves balance function.
AB  - Virtual reality is a new technology that simulates a three-dimensional virtual
      world on a computer and enables the generation of visual, audio, and haptic
      feedback for the full immersion of users. Users can interact with and observe
      objects in three-dimensional visual space without limitation. At present, virtual
      reality training has been widely used in rehabilitation therapy for balance
      dysfunction. This paper summarizes related articles and other articles suggesting
      that virtual reality training can improve balance dysfunction in patients after
      neurological diseases. When patients perform virtual reality training, the
      prefrontal, parietal cortical areas and other motor cortical networks are
      activated. These activations may be involved in the reconstruction of neurons in
      the cerebral cortex. Growing evidence from clinical studies reveals that virtual
      reality training improves the neurological function of patients with spinal cord
      injury, cerebral palsy and other neurological impairments. These findings suggest
      that virtual reality training can activate the cerebral cortex and improve the
      spatial orientation capacity of patients, thus facilitating the cortex to control
      balance and increase motion function. 

PMID- 25368652
TI  - Publication trends in studies examining radix notoginseng as a treatment for
      ischemic brain injury.
AB  - Acute ischemic stroke has become a major disease burden with high mortality and
      morbidity rates. There is a lack of evidence-based medicine confirming the
      efficacy of common treatments. Panax notoginseng saponins, the main active
      ingredient of radix notoginseng, have a neuroprotective role in ischemic brain
      injury, and have been popularized as a maintenance treatment for acute cerebral
      infarction and its sequelae. We conducted literature searches on the Web of
      Science, ClinicalTrials.gov, Cochrane Collaboration, CNKI, Wanfang and the China
      Scientific & Technological Achievements Database and analyzed the experimental
      and clinical outcomes of studies investigating the use of radix notoginseng in
      the treatment of ischemic brain injury to improve the understanding of relevant
      research trends and existing problems. We found that over the past 10 years,
      China has maintained its interest in Panax notoginseng research, while such
      studies are scarce on the Web of Science. However, Chinese researchers often
      focus on the neuroprotective role of radix notoginseng in ischemic brain injury,
      but there are no large-scale clinical data to confirm its efficacy and safety.
      There remains a need for more rigorous large-sample randomized controlled
      clinical trials with long-term follow-up, to determine whether radix notoginseng
      lowers stroke recurrence and improves patient's quality of life. 

PMID- 25368653
TI  - Stem cell transplantation for treating stroke: status, trends and development.
AB  - The developing approaches of thrombolytic therapy, endovascular treatment,
      neuroprotective therapy, and stem cell therapy have enabled breakthroughs in
      stroke treatment. In this study, we summarize and analyze trends and progress in
      stem cell transplantation for stroke treatment by retrieval of literature from
      Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant
      Program, and Clinical Trials Registration Center in North America. In the last 10
      years, there has been an increasing number of published articles on stem cell
      transplantation for stroke treatment. In particular, research from the USA and
      China has focused on stem cell transplantation. A total of 2,167 articles
      addressing stem cell transplantation for stroke treatment from 2004 to 2013 were
      retrieved from the Thomson Reuters Web of Science database. The majority of these
      articles were from the USA (854, 39.4%), with the journal Stroke publishing the
      most articles (145, 6.7%). Of the published articles, 143 were funded by the
      National Institutes of Health (accounting for 6.6% of total publications), and 91
      by the National Natural Science Foundation of China. Between 2013 and 2014, the
      National Institutes of Health provided financial support ($130 million subsidy)
      for 329 research projects on stroke therapy using stem cell transplantation. In
      2014, 215 new projects were approved, receiving grants of up to $70,440,000.
      Ninety clinical trials focusing on stem cell transplantation for stroke were
      registered in the Clinical Trial Registration Center in North America, with 40
      trials registered in the USA (ranked first place). China had the maximum number
      of registered research or clinical trials (10 projects). 

PMID- 25368654
TI  - Application of Handheld Tele-ECG for Health Care Delivery in Rural India.
AB  - Telemonitoring is a medical practice that involves remotely monitoring patients
      who are not at the same location as the health care provider. The purpose of our
      study was to use handheld tele-electrocardiogram (ECG) developed by Bhabha Atomic
      Research Center (BARC) to identify heart conditions in the rural underserved
      population where the doctor-patient ratio is low and access to health care is
      difficult. The objective of our study was clinical validation of handheld tele
      ECG as a screening tool for evaluation of cardiac diseases in the rural
      population. ECG was obtained in 450 individuals (mean age 31.49 +/- 20.058)
      residing in the periphery of Chandigarh, India, from April 2011 to March 2013,
      using the handheld tele-ECG machine. The data were then transmitted to physicians
      in Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh,
      for their expert opinion. ECG was interpreted as normal in 70% individuals. Left
      ventricular hypertrophy (9.3%) was the commonest abnormality followed closely by
      old myocardial infarction (5.3%). Patient satisfaction was reported to be ~95%.
      Thus, it can be safely concluded that tele-ECG is a portable, cost-effective, and
      convenient tool for diagnosis and monitoring of heart diseases and thus improves
      quality and accessibility, especially in rural areas. 

PMID- 25368655
TI  - Serological assay and genotyping of hepatitis C virus in infected patients in
      zanjan province.
AB  - BACKGROUND: Hepatitis C Virus (HCV), a public health problem, is an enveloped,
      single-stranded RNA virus and a member of the Hepacivirus genus of the
      Flaviviridae family. Liver cancer, cirrhosis, and end-stage liver are the
      outcomes of chronic infection with HCV. HCV isolates show significant
      heterogeneity in genetics around the world. Therefore, determining HCV genotypes
      is a vital step in determining prognosis and planning therapeutic strategies.
      OBJECTIVES: As distribution of HCV genotypes is different in various geographical
      regions and HCV genotyping of patients has not been investigated in Zanjan City,
      this study was designed for the first time, to determine HCV genotypes in the
      region and to promote the impact of the treatment. MATERIALS AND METHODS: Serum
      samples of 136 patients were collected and analyzed for anti-HCV antibodies using
      ELISA (The enzyme-linked immunosorbent assay) method. Then, positive samples were
      exposed to RT-PCR, which was performed under standard condition. Afterwards, they
      investigated for genotyping using allele-specific PCR (AS-PCR), and HCV genotype
      2.0 line probe assay (LiPA). RESULTS: Samples indicated 216 bp bands on 2%
      agarose gel. Analyses of the results demonstrated that the most dominant subtype
      was 3a with frequency of 38.26% in Zanjan Province followed by subtypes of 1b,
      1a, 2, and 4 with frequencies of 25.73%, 22.05%, 5.14%, and 4.41%, respectively.
      The frequency of unknown HCV genotypes was 4.41%. CONCLUSIONS: According to the
      results, it was found that HCV high prevalent genotype in Zanjan is subtype 3a.
      Analysis of the results provides identification of certain HCV genotypes, and
      these valuable findings could affect the type and duration of the treatment.

PMID- 25368656
TI  - Epstein-Barr Virus Infection Mimicking Drug-Induced Hepatitis in a Critically ill
      Patient During Antituberculosis Therapy.
AB  - INTRODUCTION: Although hepatitis is frequently observed during antituberculosis
      (anti-TB) therapy, acute viral hepatitis should be ruled out first, especially in
      the endemic areas. In addition to common types of viral hepatitis, ie, hepatitis
      A, hepatitis B, and hepatitis C viruses, Epstein-Barr virus (EBV) may result in
      hepatitis in some cases. CASE PRESENTATION: Herein, we reported a critically ill
      patient who developed cholestatic hepatitis in the intensive care unit during the
      anti-TB therapy, which was misdiagnosed as anti-TB agents-induced hepatitis in
      the beginning. Further serologic tests and liver biopsy confirmed the diagnosis
      of EBV hepatitis. In contrast to previously reported hepatitis by EBV, which had
      presented with transient liver dysfunction and self-limiting illness, hepatitis
      with progressive jaundice was followed by coagulopathy and encephalopathy in our
      case and the patient died of hepatic failure complications. CONCLUSIONS:
      According to the presented case and subsequent literature review on fatal EBV
      hepatitis, clinicians should consider EBV infection in the differential diagnosis
      when hepatitis occurs in critically ill patients during the anti-TB therapy.
      Although hepatitis caused by EBV is mostly self-limited, some might be fetal.

PMID- 25368657
TI  - Analysis of hepatitis e virus-like sequence in chimpanzee.

PMID- 25368658
TI  - Estrogen receptor alpha expression and liver fibrosis in chronic hepatitis C
      virus genotype 1b: a clinicopathological study.
AB  - BACKGROUND: Hepatic damage due to chronic hepatitis C virus (HCV) genotype 1b
      infection varies widely. OBJECTIVES: We aimed to investigate whether estrogen
      receptor alpha (ERalpha) plays a role in liver fibrosis in patients infected with
      HCV genotype 1b. PATIENTS AND METHODS: All the consecutive patients who received
      the same standard treatment protocol for HCV genotype 1b were subdivided into two
      subgroups according to their fibrosis scores as fibrotic stages < 2 in mild
      fibrosis group and fibrotic stages >= 2 in advanced fibrosis group, depending on
      the presence of septal fibrosis. ERalpha was stained in liver biopsy specimens.
      Demographics and clinical properties were compared between the groups.
      Multivariate logistic regression analysis was performed to predict advanced
      fibrosis. RESULTS: There were 66 patients in the mild fibrosis group and 24 in
      the advanced fibrosis group. Among the mild and advanced fibrosis groups, 65.1%
      and 50%were female, respectively (P = 0.19). There was an inverse correlation
      between ERalpha and fibrotic stage (r: -0.413; P < 0.001). Age, platelet counts,
      neutrophil counts, Alanine aminotransferase (ALT), Aspartate aminotransferase
      (AST), Gamma glutamyl transferase (GGT) and ERalpha were statistically
      significant in the univariate analysis. In multivariate logistic regression
      analyses, ERalpha expression continued to be an independent predicting factor of
      liver fibrosis in patients infected with chronic HCV genotype 1b (OR: 0.10; 95%
      CI: 0.018-0.586; P < 0.001). CONCLUSIONS: ERalpha expression in liver was
      inversely correlated with liver fibrosis among patients infected with chronic HCV
      genotype 1b.

PMID- 25368659
TI  - Long-term T-cell-mediated immunologic memory to hepatitis B vaccine in young
      adults following neonatal vaccination.
AB  - BACKGROUND: The long-term duration of cell-mediated immunity induced by neonatal
      hepatitis B virus (HBV) vaccination is unknown. OBJECTIVES: Study was designed to
      determine the cellular immunity memory status among young adults twenty years
      after infantile HB immunization. PATIENTS AND METHODS: Study subjects were party
      selected from a recent seroepidemiologic study in young adults, who had been
      vaccinated against HBV twenty years earlier. Just before and ten to 14 days after
      one dose of HBV vaccine booster injection, blood samples were obtained and sera
      concentration of cytokines (interleukin 2 and interferon) was measured. More than
      twofold increase after boosting was considered positive immune response. With
      regard to the serum level of antibody against HBV surface antigen (HBsAb) before
      boosting, the subjects were divided into four groups as follow: GI, HBsAb titer <
      2; GII, titer 2 to 9.9; GIII, titer 10 to 99; and GIV, titers >= 100 IU/L. Mean
      concentration level (MCL) of each cytokines for each group at preboosting and
      postboosting and the proportion of responders in each groups were determined.
      Paired descriptive statistical analysis method (t test) was used to compare the
      MCL of each cytokines in each and between groups and the frequency of responders
      in each group. RESULTS: Before boosting, among 176 boosted individuals, 75
      (42.6%) had HBsAb 10 IU/L and were considered seroprotected. Among 101
      serosusceptible persons, more than 80% of boosted individuals showed more than
      twofold increase in cytokines concentration, which meant positive HBsAg-specific
      cell-mediated immunity. MCL of both cytokines after boosting in GIV were
      decreased more than twofold, possibly because of recent natural boosting.
      CONCLUSIONS: Findings showed that neonatal HBV immunization was efficacious in
      inducing long-term immunity and cell-mediated immune memory for up to two
      decades, and booster vaccination are not required. Further monitoring of
      vaccinated subjects for HBV infections are recommended.

PMID- 25368660
TI  - Chronic obstructive pulmonary disease: respiratory review of 2014.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by a diverse array
      of pulmonary and nonpulmonary manifestations, but our understanding of COPD
      pathogenesis and the factors that influence its heterogeneity in disease
      presentation is poor. Despite this heterogeneity, treatment algorithms are
      primarily driven by a single measurement, forced expiratory volume in 1 second
      (FEV1) as a percentage of its predicted value (FEV1%). In 2011, a major shift in
      Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment
      recommendations was proposed that stratifies patients with COPD on the basis of
      symptoms and exacerbation history. This article reviews the work reported in 2013
      that enlightens our understanding of COPD with respect to COPD classification
      systems, phenotype, biomarker, exacerbation, and management for patients with
      COPD. 

PMID- 25368662
TI  - Effect of inhaled tiotropium on spirometric parameters in patients with
      tuberculous destroyed lung.
AB  - BACKGROUND: In Korea, patients with destroyed lung due to tuberculosis (TB)
      account for a significant portion of those affected by chronic pulmonary function
      impairment. The objective of our research was to evaluate the efficacy of inhaled
      tiotropium bromide in TB destroyed lung. METHODS: We compared the effectiveness
      of inhaled tiotropium bromide for 2 months between pre- and post-treatment
      pulmonary function tests performed on 29 patients with destroyed lung due to TB.
      RESULTS: The mean age of the total number of patients was 63+/-9 years, where 15
      patients were male. The pre-treatment mean forced expiratory volume in 1 second
      (FEV1) was 1.02+/-0.31 L (44.1+/-16.0% predicted). The pre-treatment mean forced
      vital capacity (FVC) was 1.70+/-0.54 L (52.2+/-15.8% predicted). Overall, the
      change in FEV1% predicted over baseline with tiotropium was 19.5+/-19.1%
      (p<0.001). Twenty patients (72%) got better than a 10% increase in FEV1 over
      baseline with tiotropium, but one patient showed more than a 10% decrease in
      FEV1. Overall, the change in FVC% predicted over baseline with tiotropium was
      18.5+/-19.9% (p<0.001). Seventeen patients (59%) experienced greater than a 10%
      increase in FVC over baseline with tiotropium; 12 (41%) patients had stable lung
      function. CONCLUSION: The inhaled tiotropium bromide therapy may lead to improve
      lung functions in patients with TB destroyed lung. However, the long-term
      effectiveness of this treatment still needs to be further assessed.

PMID- 25368661
TI  - Respiratory review of 2014: tuberculosis and nontuberculous mycobacterial
      pulmonary disease.
AB  - Since tuberculosis (TB) remains a major global health concern and the incidence
      of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the
      detection of TB and drug resistant TB are needed to improve TB control. The Xpert
      MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin
      resistance, with a high sensitivity and specificity. Late-generation
      fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs
      for the treatment of MDR-TB, show equally high efficacy and safety. Systemic
      steroids may reduce the overall TB mortality attributable to all forms of TB
      across all organ systems, although inhaled corticosteroids can increase the risk
      of TB development. Although fixed dose combinations were expected to reduce the
      risk of drug resistance and increase drug compliance, a recent meta-analysis
      found that they might actually increase the risk of relapse and treatment
      failure. Regarding treatment duration, patients with cavitation and culture
      positivity at 2 months of TB treatment may require more than 6 months of standard
      treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid,
      could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial
      lung disease has typical clinical and immunological phenotypes. Mycobacterial
      genotyping may predict disease progression, and whole genome sequencing may
      reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium
      avium complex lung disease, a moxifloxacin-containing regimen was expected to
      improve the treatment outcome. 

PMID- 25368663
TI  - Recurrent Pseudomonas aeruginosa Infection in Chronic Lung Diseases: Relapse or
      Reinfection?
AB  - BACKGROUND: Pseudomonas aeruginosa infection is particularly associated with
      progressive and ultimately chronic recurrent respiratory infections in chronic
      obstructive pulmonary disease, bronchiectasis, chronic destroyed lung disease,
      and cystic fibrosis. Its treatment is also very complex because of drug
      resistance and recurrence. METHODS: Forty eight cultures from 18 patients with
      recurrent P. aeruginosa pneumonia from 1998 to 2002 were included in this study.
      Two or more pairs of sputum cultures were performed during 2 or more different
      periods of recurrences. The comparison of strains was made according to the
      phenotypic patterns of antibiotic resistance and chromosomal fingerprinting by
      pulsed field gel electrophoresis (PFGE) using the genomic DNA of P. aeruginosa
      from the sputum culture. RESULTS: Phenotypic patterns of antibiotic resistance of
      P. aeruginosa were not correlated with their prior antibiotic exposition. Fifteen
      of 18 patients (83.3%) had recurrent P. aeruginosa pneumonia caused by the
      strains with same PFGE pattern. CONCLUSION: These data suggest that the most of
      the recurrent P. aeruginosa infections in chronic lung disease occurred due to
      the relapse of prior infections. Further investigations should be performed for
      assessing the molecular mechanisms of the persistent colonization and for
      determining how to eradicate clonal persistence of P. aeruginosa.

PMID- 25368664
TI  - A Case of Delayed Diagnosis of Pulmonary Paragonimiasis due to Improvement after
      Anti-tuberculosis Therapy.
AB  - Here, we report a case of pulmonary paragonimiasis that was improved with initial
      anti-tuberculosis (TB) therapy but confused with reactivated pulmonary TB. A 53
      year-old Chinese female presented with a persistent productive cough with foul
      smelling phlegm and blood streaked sputum. Radiologic findings showed subpleural
      cavitary consolidation in the right upper lobe (RUL). Bronchoscopic and
      cytological examination showed no remarkable medical feature. She was diagnosed
      with smear-negative TB, and her radiologic findings improved after receiving a 6
      month anti-TB therapy. The chest CT scans, however, obtained at 4 months after
      completion of anti-TB therapy showed a newly developed subpleural consolidation
      in the RUL. She refused pathologic confirmation and was re-treated with anti-TB
      medication. Nevertheless, her chest CT scans revealed newly developed cavitary
      nodules at 5 months after re-treatment. She underwent thoracoscopic wedge
      resection; the pathological examination reported that granuloma caused by
      Paragonimus westermani. Paragonimiasis should also be considered in patients
      assessed with smear-negative pulmonary TB. 

PMID- 25368665
TI  - Idiopathic pleuroparenchymal fibroelastosis presenting in recurrent pneumothorax:
      a case report.
AB  - Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare, recently classified
      entity that consists of pleural and subjacent parenchymal fibrosis predominantly
      in the upper lungs. In an official American Thoracic Society/European Respiratory
      Society statement in 2013, this disease is introduced as a group of rare
      idiopathic interstitial pneumonias. We describe a case of a 76-year-old woman
      with cough and recurrent pneumothorax. She was admitted to our hospital with
      severe cough at first. High resolution computed tomography (HRCT) disclosed
      multifocal subpleural consolidations with reticular opacities in both lungs,
      primarily in the upper lobes, suggesting interstitial pneumonia. Rheumatoid lung
      was diagnosed initially through an elevated rheumatoid factor, HRCT and surgical
      biopsy at the right lower lobe. However, one month later, pneumothorax recurred.
      Surgical biopsy was performed at the right upper lobe at this time. The specimens
      revealed typical subpleural fibroelastosis. We report this as a first case of
      idiopathic PPFE in Korea after reviewing the symptoms, imaging and pathologic
      findings. 

PMID- 25368666
TI  - New-onset malignant pleural effusion after abscess formation of a subcarinal
      lymph node associated with endobronchial ultrasound-guided transbronchial needle
      aspiration.
AB  - We present a case of an unusual infectious complication of a ruptured mediastinal
      abscess after endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA), which led to malignant pleural effusion in a patient with stage IIIA
      non-small-cell lung cancer. EBUS-TBNA was performed in a 48-year-old previously
      healthy male, and a mediastinal abscess developed at 4 days post-procedure. Video
      assisted thoracoscopic surgery was performed for debridement and drainage, and
      the intraoperative findings revealed a large volume pleural effusion that was not
      detected on the initial radiographic evaluation. Malignant cells were
      unexpectedly detected in the aspirated pleural fluid, which was possibly due to
      increased pleural permeability and transport of malignant cells originating in a
      ruptured subcarinal lymph node from the mediastinum to the pleural space. Hence,
      the patient was confirmed to have squamous cell lung carcinoma with malignant
      pleural effusion and his TNM staging was changed from stage IIIA to IV. 

PMID- 25368667
TI  - Successful removal of endobronchial blood clots using bronchoscopic cryotherapy
      at bedside in the intensive care unit.
AB  - Acute airway obstruction after hemoptysis occurs due to the presence of blood
      clots. These conditions may result in life-threatening ventilation impairment. We
      report a case of obstruction of the large airway by endobronchial blood clots
      which were removed using bronchoscopic cryotherapy at the bedside of intensive
      care unit. A 66-year-old female with endometrial cancer who had undergone
      chemotherapy, was admitted to the intensive care unit due to neutropenic fever.
      During mechanical ventilation, the minute ventilation dropped to inadequately low
      levels and chest radiography showed complete opacification of the left
      hemithorax. Flexible bronchoscopy revealed large blood clots obstructing the
      proximal left main bronchus. After unsuccessful attempts to remove the clots with
      bronchial lavage and forceps extraction, blood clots were removed using
      bronchoscopic cryotherapy. This report shows that cryotherapy via flexible
      bronchoscopy at the bedside in the intensive of intensive care unit is a simple
      and effective alternative for the removal of endobronchial blood clots. 

PMID- 25368668
TI  - Recurrent aggressive fibromatosis of the chest wall.
AB  - A 57-year-old woman with a previous history of aesthetic surgery for breast
      reduction presented with a subcutaneous mass in the right axilla. A CT scan
      showed a solid mass on the chest wall, and she underwent surgical resection with
      a diagnosis of aggressive fibromatosis. After a 10-month period of follow-up, a
      local recurrence occurred, and in accordance with the up-to-date approach, the
      recurrence has been treated with a conservative approach (medical treatments)
      with good control of the symptoms and downsizing of the lesion. 

PMID- 25368669
TI  - The impact of digital dissemination for research and scholarship.

PMID- 25368671
TI  - Utilization of translational bioinformatics to identify novel biomarkers of
      bortezomib resistance in multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable malignant neoplasm hallmarked by a clonal
      expansion of plasma cells, the presence of a monoclonal protein in the serum
      and/or urine (M-spike), lytic bone lesions, and end organ damage. Clinical
      outcomes for patients with MM have improved greatly over the last decade as a
      result of the re-purposing of compounds such as thalidomide derivatives, as well
      as the development of novel chemotherapeutic agents including first and second
      generation proteasome inhibitors, bortezomib (Bz) and carfilzomib. Unfortunately,
      despite these improvements, the majority of patients relapse following treatment.
      While Bz, one of the most commonly used proteasome inhibitors, has been
      successfully incorporated into clinical practice, some MM patients have de novo
      resistance to Bz, and the majority of the remainder subsequently develop drug
      resistance following treatment. A significant gap in clinical care is the lack of
      a reliable clinical test that would predict which MM patients have or will
      subsequently develop Bz resistance. Thus, as Bz resistance remains a significant
      challenge, research efforts are needed to identify novel biomarkers of early Bz
      resistance, particularly when an early therapeutic intervention can be initiated.
      Recent advances in MM research indicate that genomic data can be extracted to
      identify novel biomarkers that can be utilized to select more effective,
      personalized treatment protocols for individual patients. Computationally
      integrating large patient databases with data from whole transcriptome profiling
      and laboratory-based models can potentially revolutionize our understanding of MM
      disease mechanisms. This systems-wide approach can provide rational therapeutic
      targets and novel biomarkers of risk and treatment response. In this review, we
      discuss the use of high-content datasets (predominantly gene expression
      profiling) to identify novel biomarkers of treatment response and resistance to
      Bz in MM. 

PMID- 25368670
TI  - CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits.
AB  - BACKGROUND: Genetic understanding of complex traits has developed immensely over
      the past decade but remains hampered by incomplete descriptions of contribution
      to phenotypic variance. Gene-environment (GxE) interactions are one of these
      contributors and in the guise of diet and physical activity are important
      modulators of cardiometabolic phenotypes and ensuing diseases. RESULTS: We mined
      the scientific literature to collect GxE interactions from 386 publications for
      blood lipids, glycemic traits, obesity anthropometrics, vascular measures,
      inflammation and metabolic syndrome, and introduce CardioGxE, a gene-environment
      interaction resource. We then analyzed the genes and SNPs supporting
      cardiometabolic GxEs in order to demonstrate utility of GxE SNPs and to discern
      characteristics of these important genetic variants. We were able to draw many
      observations from our extensive analysis of GxEs. 1) The CardioGxE SNPs showed
      little overlap with variants identified by main effect GWAS, indicating the
      importance of environmental interactions with genetic factors on cardiometabolic
      traits. 2) These GxE SNPs were enriched in adaptation to climatic and
      geographical features, with implications on energy homeostasis and response to
      physical activity. 3) Comparison to gene networks responding to plasma
      cholesterol-lowering or regression of atherosclerotic plaques showed that GxE
      genes have a greater role in those responses, particularly through high-energy
      diets and fat intake, than do GWAS-identified genes for the same traits. Other
      aspects of the CardioGxE dataset were explored. CONCLUSIONS: Overall, we
      demonstrate that SNPs supporting cardiometabolic GxE interactions often exhibit
      transcriptional effects or are under positive selection. Still, not all such SNPs
      can be assigned potential functional or regulatory roles often because data are
      lacking in specific cell types or from treatments that approximate the
      environmental factor of the GxE. With research on metabolic related complex
      disease risk embarking on genome-wide GxE interaction tests, CardioGxE will be a
      useful resource.

PMID- 25368672
TI  - Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma
      of Ethanol-Preferring Rats.
AB  - Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated
      with ovarian cancer (OC) progression and metastasis, and a more complete
      understanding of these signaling pathways allow the development of new
      therapeutic strategies. Melatonin (Mel) is recognized as having several
      anticancer properties and has been reported to modulate Her-2 system in
      aggressive tumors. Here, we investigated OC and the role of Mel therapy on the
      Her-2- and Her-4-signaling pathway related to downstream molecules in an ethanol
      preferring rat model. To induce OC, the left ovary was injected directly with a
      single dose of 100 ug 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 uL of
      sesame oil under the bursa. Right ovaries were used as sham-surgery controls.
      After developing OC, half of the animals received i.p. injections of Mel (200
      ug/100 g b.w./day) for 60 days. While Mel therapy was unable to reduce Her-4 and
      phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related
      increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38
      MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR).
      In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and
      p-AKT, which are involved in OC signaling during ethanol intake. Collectively,
      our results suggest that Mel attenuates the Her-2-signaling pathway in OC of
      ethanol-preferring rats, providing an effective contribution for further
      development of adjuvant therapies. 

PMID- 25368673
TI  - Colorectal and Prostate Cancer Risk in Diabetes: Metformin, an Actor behind the
      Scene.
AB  - Both diabetes and cancer are prevalent diseases whose incidence rates are
      increasing worldwide, especially in countries that are undergoing rapid
      industrialization changes. Apparently, lifestyle risk factors including diet,
      physical inactivity and obesity play pivotal, yet preventable, roles in the
      etiology of both diseases. Epidemiological studies provide strong evidence that
      subjects with diabetes are at significantly higher risk of developing many forms
      of cancer and especially solid tumors. In addition to pancreatic and breast
      cancer, the incidence of colorectal cancer and prostate cancer is increased in
      type 2 diabetes. While diabetes (type 2) and cancer share many risk factors, the
      biological links between the two diseases are poorly characterized. In this
      review, we highlight the mechanistic pathways that link diabetes to colorectal
      and prostate cancer and the use of Metformin, a diabetes drug, to prevent and/or
      treat colorectal and prostate cancer. We review the role of AMPK activation in
      autophagy, oxidative stress, inflammation, apoptosis, and cell cycle progression.

PMID- 25368674
TI  - cMET Activation and EGFR-Directed Therapy Resistance in Triple-Negative Breast
      Cancer.
AB  - BACKGROUND: EGFR expression and pathway activation are common in triple-negative
      breast cancer (TNBC). However, anti-EGFR therapies have not been effective in
      these patients. We aimed to study the efficacy of targeting MET in overcoming
      resistance to EGFR therapy in TNBC cell lines. METHODS: TNBC lines (MDA-MB-468,
      HCC-1395, and MDA-MB-231), and a hormone receptor-positive breast cancer line
      (T47D) were stimulated with epidermal growth factor (EGF) and hepatocyte growth
      factor (HGF). Lines were then treated with different concentrations of EGFR
      inhibitors (gefitinib or cetuximab), with or without a MET tyrosine kinase
      inhibitor (EMD 1214063). Proliferation was measured by MTS assay, in soft agar
      and with a matrigel assay. Synergy was measured with Calcusyn. Protein expression
      and signaling were examined with immunoblotting. RESULTS: There was activation of
      ligand-receptor-downstream signaling pathways in MDA-MB-468 and HCC-1395 upon
      stimulation with EGF and HGF. In these cell lines, we observed synergism when
      combining EGFR and MET inhibitors. These results were observed across assays. In
      western blotting, combination therapy resulted in abrogation of pAKT and pMAPK
      while monotherapy did not. CONCLUSION: Our data demonstrate that dual EGFR/MET
      inhibition is synergistic in TNBC. Targeting both EGFR and MET receptors may
      provide an effective therapeutic strategy in TNBC.

PMID- 25368675
TI  - Perineural Invasion and TAMs in Pancreatic Ductal Adenocarcinomas: Review of the
      Original Pathology Reports Using Immunohistochemical Enhancement and
      Relationships with Clinicopathological Features.
AB  - OBJECTIVES: Tumor-associated macrophages (TAMs) are thought to be involved in the
      perineural invasion (PNI) process and to be associated with poor prognoses. The
      associations between TAMs, PNI, and clinicopathological features in pancreatic
      ductal adenocarcinomas (PDAs) remain to be elucidated. METHODS: Fifty-nine PDA
      patients who had undergone pancreaticoduodenectomy were retrospectively examined.
      The PNI statuses and TAMs were reviewed following H&E staining and S-100, CD68,
      and CD163 immunohistochemical staining. The relationships between PNI, TAMs, and
      overall survival and various clinical and histopathologic factors were
      investigated. RESULTS: PNI was identified in 83% (49/59) of the cases, the TAM
      density of the PNI(+) group was greater than that of the PNI(-) group, and the
      infiltrating TAMs around the nerves that were invaded by cancer were much more
      numerous than those around the nerves without cancer cell invasion. The
      incidences of PNI, lymph node metastasis, high serum CA19-9 level, cancers in the
      body/tail, and advanced pathological stage were associated with shorter OSs. In
      the PNI(+) group, lymph node metastasis and high levels of TAM infiltration were
      associated with worse prognoses. CONCLUSIONS: TAMs might enhance PNI, and the
      incidence of PNI was associated with poor prognosis. PNI(+) status and high
      levels of TAM infiltration further worsen the prognosis. Therapies targeting TAMs
      might represent auxiliary and preventive treatment for PNI in PDA patients.

PMID- 25368676
TI  - CD70: A Potential Target in Breast Cancer?
AB  - CD70 is a co-stimulatory molecule involved in the immune response and also in
      cancer development and progression. Recent studies show that high CD70 expression
      in cancer cells may inhibit the anti-tumor response. Furthermore, CD70 expression
      has been reported as a predictive marker of resistance to chemotherapy in ovarian
      cancers. Some in vitro studies have shown that CD70 expression is epigenetically
      down-regulated through hypermethylation of its promoter during tumoral
      progression. This study evaluated the level of CD70 expression in surgical
      samples of breast invasive tumors and determined its correlation with CD70
      promoter methylation. Twenty "luminal A" and 20 "basal-like" frozen samples from
      early breast tumors were retrospectively selected. CD70 expression was evaluated
      by quantitative real-time PCR. Total DNA was bisulfite-treated, and methylation
      levels of 5 consecutive CG sites present in the proximal region (-464, -421) of
      the promoter were assessed by pyrosequencing analysis. Statistical analyses were
      performed using the Mann-Whitney test. The median relative CD70 expression level
      was 0.37 and was significantly higher in the basal-like group (0.78 [0.24-31.7])
      compared to the luminal A group (0.25 [0.03-1.83], p=0.0001). The median
      methylation level was 61%, with no significant difference between the basal-like
      (63%) and luminal A (58%) groups. No correlation was found between CD70
      expression and CD70 methylation level. In this study, higher CD70 expression was
      observed in the basal-like group, but this expression was not related to promoter
      methylation. The higher expression in the poor-prognosis subgroup of patients
      makes CD70 a potential target for emerging anti-CD70 therapies. 

PMID- 25368678
TI  - In vivo lymphatic imaging of a human inflammatory breast cancer model.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) remains the most aggressive type of
      breast cancer with the greatest potential for metastasis and as a result, the
      highest mortality rate. IBC cells invade and metastasize through dermal lymphatic
      vessels; however, it is unknown how lymphatic drainage patterns change during IBC
      growth and metastasis. Herein, we non-invasively and longitudinally imaged
      lymphatics in an animal model of IBC using near-infrared fluorescence (NIRF)
      imaging. MATERIALS AND METHODS: Mice were imaged in vivo prior to, and up to 11
      weeks after subcutaneous or orthotopic inoculation of human IBC SUM149 cells,
      which were stably transfected with infrared fluorescence protein (iRFP) gene
      reporter (SUM149-iRFP), following intradermal (i.d.) injection of indocyanine
      green (ICG). RESULTS: Fluorescence images showed well-defined lymphatic vessels
      prior to SUM149-iRFP inoculation. However, altered lymphatic drainage patterns
      including rerouting of lymphatic drainage were detected in mice with SUM149-iRFP,
      due to lymphatic obstruction of normal lymphatic drainages caused by tumor
      growth. In addition, we observed tortuous lymphatic vessels and extravasation of
      ICG-laden lymph in mice with SUM149-iRFP. We also observed increased and dilated
      fluorescent lymphatic vessels in the tumor periphery, which was confirmed by ex
      vivo immunohistochemical staining of lymphatic vessels. CONCLUSIONS: Our pre
      clinical studies demonstrate that non-invasive NIRF imaging can provide a method
      to assess changes in lymphatic drainage patterns during IBC growth and
      metastasis.

PMID- 25368677
TI  - Interleukin-7 and interleukin-15 for cancer.
AB  - Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they
      have the ability to destabilize chromosomes and induce tumorigenesis.
      Additionally, they can control malignancy proliferation by influencing the tumor
      microenvironment and immune system. Immunotherapy has been proposed as a
      treatment modality for malignancy for over a decade; the exact mechanisms of
      action and pathways are still under investigation. Interleukin 7 and 15 have been
      extensively investigated in hematological malignancies since their mode of action
      influences the stimulation of the immune system in a more direct way than other
      malignancies such as lung, melanoma, and breast, renal and colorectal cancer. 

PMID- 25368679
TI  - The Cause and Prevention of Anastomotic Recurrence following Colectomy: An
      Immunohistochemical Approach for Detecting Transforming Colonocytes.
AB  - With the ability to identify the presence of transforming colonocytes in a field
      adjacent to an existing primary colon cancer, it is now possible to reduce if not
      eliminate one of the major causes leading to anastomotic tumor recurrence. In a
      review of those colectomy cases that presented post-surgery with anastomotic
      recurrence, we noted that mucosal abnormalities could readily be detected
      adjacent to the primary lesion. Such changes had gone unrecognized at the time of
      surgery, when standard histologic procedures were employed. By utilizing
      monoclonal antibodies (mAbs) that defined the presence of tumor immunogenic
      proteins, we were able to reexamine so-called normal biopsy sites adjacent to the
      tumor. Here, it was possible to demonstrate the presence of altered cellular
      activity in existing phenotypically normal appearing colonocytes that were in the
      process of transforming to malignancy. Eight consecutive patients that had been
      admitted for evaluation and resection of an anastomotic recurrence post
      colectomy, were studied with regard to possible etiologic factors. The original
      margins incorporated into the anastomosis were re-examined by
      immunohistochemistry employing those monoclonal antibodies (mAbs) designed to
      target colon tumor antigen. This antigen had previously been shown to be
      expressed only in colon cancer and not in adjacent normal tissue. In addition,
      biopsies from margins of resection in five patients free of recurrence following
      colectomy were also studied along with colon specimens from 50 normal patients,
      non-demonstrating expression of tumor antigen in the normal appearing
      colonocytes. In each of the patients who had presented with anastomotic
      recurrence, normal appearing colonocytes defined by light microscopy and found
      adjacent to the previously resected primary lesion, expressed tumor antigen. The
      antigen detected in these colonocytes proved to be identical to antigen expressed
      in the anastomotic recurrence giving credence to the concept that these normal
      appearing cells in proximity to the tumor were responsible for the regrowth of
      tumor in the suture line used to establish continuity of the bowel. Based on the
      findings of this preliminary retrospective study it is felt that at the time of
      performing a colectomy for a malignant lesion of the bowel, that it is important
      that those normal appearing colonocytes adjacent to tumor be evaluated for
      expression of tumor associated antigen. Excluding such cells from an anastomosis,
      may help to assure that tumor recurrence will be minimized if not totally
      eliminated. 

PMID- 25368680
TI  - Amplification of Chromosome 1q Genes Encoding the Phosphoinositide Signalling
      Enzymes PI4KB, AKT3, PIP5K1A and PI3KC2B in Breast Cancer.
AB  - Little is known about the possible oncogenic roles of genes encoding for the
      phosphatidylinositol 4-kinases, a family of enzymes that regulate an early step
      in phosphoinositide signalling. To address this issue, the mutational status of
      all four human phosphatidylinositol 4-kinases genes was analyzed across 852
      breast cancer samples using the COSMIC data resource. Point mutations in the
      phosphatidylinositol 4-kinase genes were uncommon and appeared in less than 1% of
      the patient samples however, 62% of the tumours had increases in gene copy number
      for PI4KB which encodes the phosphatidylinositol 4-kinase IIIbeta isozyme.
      Extending this analysis to subsequent enzymes in the phosphoinositide signalling
      cascades revealed that the only PIP5K1A, PI3KC2B and AKT3 genes exhibited similar
      patterns of gene copy number variation. By comparison, gene copy number increases
      for established oncogenes such as EGFR and HER2/Neu were only evident in 20% of
      the samples. The PI4KB, PIP5K1A, PI3KC2B and AKT3 genes are related in that they
      all localize to chromosome 1q which is often structurally and numerically
      abnormal in breast cancer. These results demonstrate that a gene quartet encoding
      a potential phosphoinositide signalling pathway is amplified in a subset of
      breast cancers. 

PMID- 25368681
TI  - Acute Changes in Ambient Temperature Are Associated With Adverse Changes in
      Cardiac Rhythm.
AB  - BACKGROUND: Both increases and decreases in ambient temperature have been
      associated with increased cardiovascular mortality and morbidity. However, the
      mechanism(s) remain unclear. OBJECTIVES: We examined associations between
      biomarkers of pathways thought to, in part, explain these associations and
      changes in ambient temperature in a panel of predominantly post-myocardial
      infarction or post-stent patients. METHODS: We studied 76 subjects who had a
      recent coronary event and were participating in a cardiac rehabilitation program.
      In these patients, we measured heart rate variability, repolarization, and
      baroreflex sensitivity parameters using Holter ECG recordings before and during
      supervised, graded, twice weekly, exercise sessions. Hourly temperature
      measurements were made at a monitoring site near the rehabilitation center.
      RESULTS: Using linear mixed models, we observed decreases in rMSSD (square root
      of the mean of the sum of the squared differences between adjacent NN intervals)
      and deceleration capacity, associated with increases in ambient temperature in
      the previous four days. Additionally, decreased rMSSD was associated with both
      increasing temperature (mean in previous 6 hours) in the summer and decreasing
      temperature (mean in the previous 3 weeks) in the winter. CONCLUSIONS: In a panel
      of cardiac rehabilitation patients, changes in ambient temperature were
      associated with decreases in markers of heart rate variability and baroreflex
      sensitivity, which may lead to increased risk of arrhythmic events and sudden
      death in post-infarction patients.

PMID- 25368682
TI  - Color Doppler ultrasound and arteriovenous fistulas for hemodialysis.
AB  - Native arteriovenous fistula (AVF) is the vascular access of choice for
      hemodialysis patients. Compared with grafts and central venous catheters, AVFs
      last longer and are associated with fewer complications. The widespread use of
      the Doppler ultrasound (DUS) has increased the number of patients who are
      eligible for AVF by facilitating the identification of vessels that are suitable
      for fistula construction (preoperative vascular mapping). DUS can also extend
      native AVF survival by improving the early detection of complications (post
      operative surveillance). It is the only imaging modality that furnishes both
      morphological and functional data on the native vascular access, and it is also
      the only imaging tool that can be used directly by the surgeon, an indisputable
      advantage. This review examines the numerous roles played by DUS in the
      construction and postoperative follow-up of AVFs, including preoperative vascular
      mapping, AVF maturation, and surveillance. 

PMID- 25368683
TI  - Technical feasibility of real-time elastography to assess the peri-oral region in
      patients affected by systemic sclerosis.
AB  - PURPOSE: To evaluate the technical feasibility of real-time elastography (RTE) to
      assess the stiffness of the skin of the peri-oral region in patients affected by
      systemic sclerosis (SSc). METHODS: Six female patients affected by SSc (median
      age = 52 years) presenting with microstomia and six healthy controls matched for
      age and sex underwent RTE evaluation of the peri-oral region. Two operators with
      different experience evaluated the stiffness of the peri-oral region placing the
      probe in four different positions: parasagittal left (PL), parasagittal right
      (PR), upper axial (UA), lower axial (LA). Color map was converted into a semi
      quantitative scale in which blue = 1, green = 2 and red = 3. Thus, each subject
      had a variable score ranging from 4 (four positions * value = 1) and 12 (four
      positions * value = 3). Mann-Whitney U and k statistics were used. RESULTS: RTE
      demonstrated that the skin of the peri-oral region of patients affected by SSc
      was stiffer than that of controls, both overall (6;4-6 [median; 25-75th
      percentile] vs. 11;9-11, p < 0.001) and for each probe position (PL = 1;1-2 vs.
      2;2-3, PR = 1;1-2 vs. 2;2-3, UA = 1;1-2 vs. 2;2-3; LA = 1;1-1 vs. 3;3-3, p <=
      0.011 for all). Interobserver reproducibility was excellent both overall and for
      each probe position (k = 1). CONCLUSION: RTE is a feasible modality to assess
      peri-oral region skin stiffness with excellent interobserver reproducibility.
      Further studies on a larger cohort of patients including more clinical data and
      measures are warranted to confirm our initial results.

PMID- 25368684
TI  - Sonoelastography findings of biceps tendinitis and tendinosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate sonoelastography (SE) in the
      assessment of the long head of biceps tendon (LHBT) in patients with symptoms of
      biceps tendinitis or tendinosis and in patients without biceps lesion. The
      findings were compared with those obtained at clinical examination, using
      ultrasonography (US). MATERIALS AND METHODS: 36 shoulders of 34 consecutively
      registered patients with clinical symptoms and US findings of biceps tendinitis
      or tendinosis, and 114 shoulders of 98 patients without biceps lesions were
      assessed with SE. Transverse and longitudinal images of LHBT were obtained using
      SE. SE images were evaluated by reviewers using an experimentally proven color
      grading system. RESULTS: The transverse images of SE showed a mean sensitivity of
      69.4 %, a mean specificity of 95.6 % and a mean accuracy of 89.3 %. Good
      correlation of conventional ultrasound findings was found (p < 0.001, r = 0.763).
      The longitudinal images of SE showed a mean sensitivity of 94.4 %, a mean
      specificity of 92.1 % and a mean accuracy of 92.7 %. Good correlation of
      conventional ultrasound findings was found (p < 0.001, r = 0.585). Inter-observer
      reliability of SE was in "almost perfect agreement" with a weighted kappa
      coefficient of 0.84. CONCLUSIONS: SE has potential to be clinically useful in the
      detection of the intratendinous and peritendinous alterations of LHBT and has
      excellent accuracy and excellent correlation with conventional ultrasound
      findings.

PMID- 25368685
TI  - The accuracy of sonoelastography in fatty degeneration of the supraspinatus: a
      comparison of magnetic resonance imaging and conventional ultrasonography.
AB  - OBJECTIVE: Sonolastography (SE) technique is one of the new functional ultrasonic
      imaging techniques, which was developed in the past few years and can obtain the
      distributions of elasticity in tissues. Using magnetic resonance imaging (MRI) as
      the standard of reference, the purpose of this study was to evaluate the ability
      of SE to assess the fatty degeneration of suprasupinatus (SSP) and to compare it
      to the MRI and the conventional ultrasonography (US) findings. MATERIALS AND
      METHODS: The institutional review board approved the study, and a retrospective
      analysis between January 2013 and September 2013 was performed on 101 shoulders
      of 98 consecutive patients using MRI, US, and SE for the evaluation of shoulder
      lesion. Oblique sagittal images of SSP were obtained using SE. The SE images were
      evaluated by reviewers using an experimentally proven color grading system.
      RESULTS: When comparing SE to standard MRI findings, the mean sensitivity of SE
      was 95.6 %, the specificity 87.5 %, and the accuracy 91.1 %. The interobserver
      reliability of the SE findings was "almost perfect agreement" with a weighted
      kappa coefficient of 0.81. On comparing MRI with the SE findings, the grades of
      MRI and SE have a positive correlation (r = 0.855, P = <0.001). Furthermore, the
      grades of US and SE also have a positive correlation (r = 0.793, P = <0.001).
      CONCLUSION: SE is valuable in the quantitative assessment of the severity of the
      fatty atrophy of the supraspinatus and has an excellent accuracy, an excellent
      correlation with MRI and the conventional US, and an excellent interobserver
      reliability.

PMID- 25368686
TI  - Doppler ultrasonographic evaluation of ductus venosus blood flow in 55 canine
      fetuses.
AB  - PURPOSE: The ductus venosus (DV) blood flow has been studied in fetal lambs and
      in humans. This study aims to describe the velocities, the Doppler indices and
      the morphological patterns of the venous blood flow in the DV of canine fetuses
      during physiological pregnancy. METHODS: The DV of 55 canine fetuses has been
      evaluated and the waveforms described using B-mode, color and pulsed-wave Doppler
      ultrasound technology. RESULTS: We found 48 diphasic waves and 7 threephasic
      waves. No monophasic waveform was found. Six of seven threephasic waveforms
      belonged to litters in which perinatal mortality occurred. The peak velocity
      during ventricular systole S (cm/s), the peak velocity during the ventricular
      diastole D (cm/s), the velocity during atrial contraction aV (cm/s), the S/D
      index, the pulsatility index (PI) and the resistance index were measured.
      CONCLUSIONS: All Doppler indices and velocities were significantly correlated
      with each other (p < 0.05). The number of newborn puppies and the age of bitches
      were not related to DV vascular indices or flow rate (p > 0.05). Gestational age
      was proportional to the PI (p < 0.02). Doppler ultrasonography allows the
      assessment of DV blood flow in canine fetuses during pregnancy.

PMID- 25368687
TI  - Two ductus venosus: a previously unreported anomaly.
AB  - In early fetal life, the ductus venosus (DV) connects the umbilical vein,
      carrying nutrient-rich and oxygenated blood from the placenta to the inferior
      vena cava (IVC). We present the first ever case of a fetus with two ductus
      venosus. The fetus presented with a four-vessel cord and a dilated bowel at 31
      weeks of gestation. Ultrasonography showed a persistent right umbilical vein.
      Echocardiographic investigation revealed normal cardiac anatomy with no major
      malformations. Two DVs with slightly different Doppler patterns were visualized
      anastomosing with the IVC. The baby was born uneventfully at 39 weeks of
      gestation with stable hemodynamics. Assuming every supernumerary umbilical vein
      should be connected to a DV for balanced circulation, a fetus with supernumerary
      umbilical veins lacking a corresponding number of DV connections is likely to be
      predisposed to complications such as hydrops fetalis and poor perinatal outcomes.
      The possibility of one or more umbilical veins lacking a DV connection warrants
      significant attention and regular monitoring from feto-maternal specialists,
      given the severity of the associated morbidity and mortality. 

PMID- 25368688
TI  - Vein of Galen arteriovenous malformation mimicking coarctation of the aorta.
AB  - Arteriovenous malformation of the vein of Galen is a rare congenital intracranial
      anomaly lacking a capillary bed and subsequent aneurysmal enlargement of the
      arterial and venous system, warranting careful management due to associated
      morbidity and mortality. Coarctations of aorta demonstrate similar neonatal
      echocardiographic signs to the vein of Galen arterial malformation (VGAM). We
      present a boy at 37 weeks of gestation whose initial ultrasound and
      echocardiographic investigations showed a dominant right ventricle and isthmal
      hypoplasia, suggestive of coarctation of aorta. Follow-up ultrasound and
      echocardiography revealed an arteriovenous malformation involving middle and
      posterior cerebral artery branches, eliminating coarctation of aorta. VGAM was
      confirmed by further ultrasound and angiographic investigation, which
      demonstrated a tangle of cerebral and choroidal arterial branches centrally
      feeding into an enlarged vein of Galen. The boy's hemodynamic and neurological
      statuses were confirmed to be stable despite increased venous pressure. Elective
      embolization at 7 months of age was complicated by a cerebrovascular accident,
      resulting in right hemiparesis despite no residual cardiac issues. This case
      demonstrates that rarely, arteriovenous malformations such as the vein of Galen
      malformations may be the primary cause of patients presenting with coarctation of
      aorta. The rarity of this condition and its guarded prognosis make our case of
      special interest to cardiologists and the perinatal care team. 

PMID- 25368689
TI  - A clinical case of Fournier's gangrene: imaging ultrasound.
AB  - Fournier's gangrene is a rapidly progressing necrotizing fasciitis involving the
      perineal, perianal, or genital regions and constitutes a true surgical emergency
      with a potentially high mortality rate. Although the diagnosis of Fournier's
      gangrene is often made clinically, emergency ultrasonography and computed
      tomography lead to an early diagnosis with accurate assessment of disease extent.
      The Authors report their experience in ultrasound diagnosis of one case of
      Fournier's gangrene of testis illustrating the main sonographic signs and imaging
      diagnostic protocol. 

PMID- 25368690
TI  - Contrast-enhanced ultrasound (CEUS) appearances of an adrenal phaeochromocytoma
      in a child with Von Hippel-Lindau disease.
AB  - A phaeochromocytoma is a rare catecholamine-secreting tumour arising from the
      chromaffin cells. We describe a case of a child with Von Hippel-Lindau disease,
      with an adrenal phaeochromocytoma who presented with severe dilated
      cardiomyopathy driven by secondary hypertension. Contrast-enhanced ultrasound
      findings are described and compared with both magnetic resonance imaging and
      computed tomography imaging. 

PMID- 25368691
TI  - The "whirlpool sign", a US finding in partial torsion of the spermatic cord: 4
      cases.

PMID- 25368692
TI  - Sonography of the nasal cartilage: technique and normal anatomy.
AB  - The cartilagineous parts of the nose may be involved in a wide range of
      pathologies ranging from trauma and infection to malignancy. If pathology is
      suspected on examination, an easy-to-use imaging modality would be helpful in
      everyday clinical work. Until now, sonography of the nasal cartilage has not been
      described. This short letter describes the technique and normal anatomy of the
      nasal cartilage on sonography. Sonography may evolve into a powerful imaging tool
      in imaging of the nasal cartilage. 

PMID- 25368693
TI  - Feasibility of real-time strain elastography in colonic diseases.
AB  - Real-time strain elastography is not routinely performed in clinical practice for
      characterizing gastrointestinal tract diseases, and there are few studies in the
      literature on the subject. The recent EFSUMB guidelines suggest the use of this
      method in the diagnosis of neoplastic lesions and in the characterization of
      bowel strictures in patients with Crohn's disease. The purpose of this pictorial
      essay is to evaluate the feasibility of strain elastography in some pathologies
      of the colon frequently encountered in daily clinical practice and to compare
      elastography images with corresponding endoscopic and radiographic images. In our
      opinion, strain elastography is useful for characterizing diseases of the colon
      as it can add valuable diagnostic information to grayscale ultrasound imaging.
      However, diagnostic accuracy and clinical relevance of this information should be
      confirmed by further prospective research-targeted studies. 

PMID- 25368694
TI  - Anesthetic considerations on adrenal gland surgery.
AB  - Adrenal gland surgery needs a multidisciplinary team including endocrinologist,
      radiologist, anesthesiologist, and surgeon. The indications for adrenal gland
      surgery include hormonal secreting and non-hormonal secreting tumors. Adrenal
      hormonal secreting tumors present to the anesthesiologist unique challenges
      requiring good preoperative evaluation, perioperative hemodynamic control,
      corrections of all electrolytes and metabolic abnormalities, a detailed and
      careful anesthetic strategy, overall knowledge about the specific diseases,
      control and maintaining of postoperative adrenal function, and finally a good
      collaboration with other involved colleagues. This review will focus on the
      endocrine issues, as well as on the above-mentioned aspects of anesthetic
      management during hormone secreting adrenal gland tumor resection. 

PMID- 25368695
TI  - Effects of intake of fish or fish oils on the development of diabetes.
AB  - The association between fish and fish oils intake and diabetes remains largely
      unknown. Here we systematically reviewed published articles (clinical trials,
      prospective cohort studies, systematic reviews and meta-analyses) about the
      effects of intake of fish or fish oils on the development of diabetes. An intake
      of fish oils seems not to affect insulin sensitivity, insulin secretion, beta
      cell function or glucose tolerance. There is a considerable statistical
      heterogeneity in the overall summary estimates of the association between fish or
      fish oils consumption and the development of type 2 diabetes, which is partly
      explained by geographical differences. Marine n-3 polyunsaturated fatty acids
      have beneficial effects on the prevention of type 2 diabetes in Asian
      populations. 

PMID- 25368696
TI  - Sepsis in the neurologic intensive care unit: epidemiology and outcome.
AB  - BACKGROUND: Sepsis is a major contributor to mortality in patients admitted to a
      general intensive care unit (ICU). Early recognition and treatment of sepsis is
      key in improving outcomes. The epidemiology and outcome of sepsis in neurologic
      ICU (NeuroICU) has not been evaluated. METHODS: We retrospectively identified all
      patients admitted to our 16-bed NeuroICU between June 2009 and December 2013
      using the acute physiologic and chronic health evaluation (APACHE) outcomes
      database. We excluded patients admitted with an infection, such as meningitis,
      encephalitis, brain or spinal abscess, or with any other infection. We compared
      NeuroICU patients who did to NeuroICU patients who did not develop sepsis after
      ICU admission. The diagnosis of sepsis was based on the SCCM/ACCP consensus
      conference definition. RESULTS: There were a total of 2,025 patients, out of
      which 29 patients (1.4%) developed sepsis. Patients who developed sepsis had a
      trend towards older age (67 +/- 13 vs. 61 +/- 11 years, P = 0.07), a trend
      towards more male gender (69.0% vs. 51.5%, P = 0.07), significantly higher APACHE
      III scores (58 +/- 17 vs. 43 +/- 21, P = 0.0001), and significantly higher acute
      physiologic scores (APS) (43 +/- 16 vs. 32 +/- 18, P = 0.001) than patients who
      did not develop sepsis. Patients who developed sepsis had higher ICU mortality
      (41.4% vs. 5.1%, odds ratio (OR) = 13.1; 95% confidence interval (CI), 6.1 -
      28.2, P < 0.0001), and higher hospital mortality (44.8% vs. 8.2%, OR = 9.0; 95%
      CI, 4.3 - 19.0, P < 0.0001). CONCLUSIONS: Sepsis developed in 1.4% of patients
      admitted to a NeuroICU. Predictors of sepsis development were comorbidities and
      worsening acute physiologic variables. Patients who developed sepsis had
      significantly higher mortality. Vigilance to development of sepsis in NeuroICU is
      paramount, especially in this era when early recognition and intervention of
      sepsis significantly improves outcomes.

PMID- 25368698
TI  - Investigating the relationship between persistent reflux flow on the first
      postoperative day and recurrent varicocele in varicocelectomy patients.
AB  - BACKGROUND: The aim of this study was to investigate the presence of persistent
      reflux flow on the first postoperative day using color Doppler sonography (CDS)
      in patients who had undergone sub-inguinal varicocelectomy, and to research the
      relationship between persistent reflux flow and recurrent varicocele. METHODS: A
      total of 54 patients were included in the study. Ages of the patients were
      between 21 and 38 years (mean 27.3 +/- 7.6). All patients were evaluated four
      times with CDS: preoperatively, first postoperative day, 3 months postoperative,
      and finally 6 months after the operation. RESULTS: Preoperative venous diameters
      were measured between 3 and 5.5 mm; mean vein diameters were 3.8 +/- 0.7 mm for
      the left side and 3.4 +/- 0.4 mm for the right side. Mean duration of reflux was
      3.5 +/- 0.3 seconds on the left side and 2.9 +/- 0.7 seconds on the right side.
      First postoperative day persistent Valsalva-induced reflux flow was seen in 10
      patients (18%). Mean venous diameter was measured 1.8 +/- 0.9 mm. Three months
      after the operation, Valsalva-induced reflux flow was seen in two patients (3%)
      in whom reflux was not seen on the first postoperative day. After 6 months,
      venous diameters larger than 2 mm at rest and the occurrence of reflux during the
      Valsalva maneuver were considered to be a recurrence. Six months after the
      operation, 12 patients had recurrent varicocele. Detecting persistent reflux with
      CDS on the first postoperative day was found to be 85% sensitive and 100%
      specific for showing recurrence. CONCLUSION: Valsalva-induced persistent reflux
      flow investigated with CDS on the first postoperative day can be used to show
      success of the surgery and is also an indicator of recurrence in varicocelectomy
      patients.

PMID- 25368697
TI  - Validity and reliability of the European portuguese version of neuropsychiatric
      inventory in an institutionalized sample.
AB  - BACKGROUND: Neuropsychiatric symptoms are very common in dementia and have been
      associated with patient and caregiver distress, increased risk of
      institutionalization and higher costs of care. In this context, the
      neuropsychiatric inventory (NPI) is the most widely used comprehensive tool
      designed to measure neuropsychiatric Symptoms in geriatric patients with
      dementia. The aim of this study was to present the validity and reliability of
      the European Portuguese version of NPI. METHODS: A cross-sectional study was
      carried out with a convenience sample of institutionalized patients (>= 50 years
      old) in three nursing homes in Portugal. All patients were also assessed with
      mini-mental state examination (MMSE) (cognition), geriatric depression scale
      (GDS) (depression) and adults and older adults functional assessment inventory
      (IAFAI) (functionality). NPI was administered to a formal caregiver, usually from
      the clinical staff. Inter-rater and test-retest reliability were assessed in a
      subsample of 25 randomly selected subjects. RESULTS: The sample included 166
      elderly, with a mean age of 80.9 (standard deviation: 10.2) years. Three out of
      the NPI behavioral items had negative correlations with MMSE: delusions (rs = 
      0.177, P = 0.024), disinhibition (rs = -0.174, P = 0.026) and aberrant motor
      activity (rs = -0.182, P = 0.020). The NPI subsection of depression/dysphoria
      correlated positively with GDS total score (rs = 0.166, P = 0.038). NPI showed
      good internal consistency (overall alpha = 0.766; frequency alpha = 0.737;
      severity alpha = 0.734). The inter-rater reliability was excellent (intraclass
      correlation coefficient (ICC): 1.00, 95% confidence interval (CI) 1.00 - 1.00),
      as well as test-retest reliability (ICC: 0.91, 95% CI 0.80 - 0.96). CONCLUSION:
      The results found for convergent validity, inter-rater and test-retest
      reliability, showed that this version appears to be a valid and reliable
      instrument for evaluation of neuropsychiatric symptoms in institutionalized
      elderly.

PMID- 25368700
TI  - Treatment of iron deficiency with intravenous ferric carboxymaltose in general
      practice: a retrospective database study.
AB  - BACKGROUND: Iron deficiency is a frequent problem in general practice. Oral
      supplementation may in some cases not be well tolerated or not be efficient.
      Intravenous ferric carboxymaltose may be an alternative for iron supplementation
      in general practice. The aim of the present study was to analyze the indications
      for and the efficacy of intravenous ferric carboxymaltose in a primary care
      center. METHODS: We retropectively analyzed electronic data from 173 patients
      given intravenous ferric carboxymaltose between 2011 and 2013 in primary care
      center with 18 GPs in Bern, Switzerland. RESULTS: Of all patients, 34% were
      treated intravenously due to an inappropriate increase in ferritin levels after
      oral therapy, 24% had side effects from oral treatment, 10% were treated
      intravenously due to the patients explicit wish, and in 39% of all cases, no
      obvious reason of intravenous instead of oral treatment could be found.
      Intravenous ferric carboxymaltose led to a significant increase in hemoglobin and
      serum ferritin levels. Side effects of intravenous treatment were found in 2% of
      all cases. CONCLUSION: We conclude that treatment with intravenous ferric
      carboxymaltose is an efficient alternative for patients with iron deficiency in
      general practice, when oral products are not well tolarated or effective. As
      treatment with iron carboxymaltose is more expensive and potentially dangerous
      due to side effects, the indication should be placed with (more) care.

PMID- 25368699
TI  - Clinical markers of Crohn's disease severity and their association with opiate
      use.
AB  - BACKGROUND: The safety of opiate use for patients with Crohn's disease (CD) has
      long been a concern. The recent Crohn's therapy, resource, evaluation, and
      assessment tool (TREAT) registry update has added to these concerns by
      demonstrating an association of opiate use with an increased risk of infection
      and death in CD. While the association is clear, the relationship of opiates to
      these negative outcomes is not. It is unknown whether opiates are a contributing
      factor to these negative outcomes or if their use is merely a marker of more
      severe disease. We hypothesized that opiate use is not harmful in CD but is a
      marker of disease severity and would be associated with commonly accepted
      clinical markers of severe CD such as early age at CD onset, disease duration,
      small intestinal involvement, a history of fistula or stricture, and lower
      quality of life (QOL) scores. METHODS: Data on CD history including pain
      medication usage were obtained from an interviewer directed survey of patients
      admitted to two tertiary care hospitals over a 2-year period. CD as the primary
      admitting diagnosis was not required. Active opiate use was defined by usage
      within the past month prior to admission. RESULTS: A total of 133 patients were
      approached to participate, of whom 108 consented to the survey, and 51 were
      active opiate users. Opiate using CD patients were more commonly smokers (22% vs.
      3.45%, P < 0.010), had fistulas (40% vs. 22.4%, P < 0.048) and had a poorer
      quality of life score by short form inflammatory bowel disease questionnaire
      (mean 3.80 vs. 4.34, P < 0.036) than non-opiate users. No difference was found
      between opiate users and non-users for age of diagnosis, disease duration, or a
      history of strictures. CONCLUSIONS: The study findings demonstrate that opiate
      use in CD is associated with markers of disease severity including fistulas,
      smoking, and lower QOL scores. The findings suggest that opiates may not be
      directly harmful to patients with CD, but may merely be another marker of disease
      severity. However, given opiates unproven benefits for long term CD pain control
      and risk of dependence, caution should still be exercised in their use.

PMID- 25368701
TI  - Hyaluronic Acid concentration in pleural fluid: diagnostic aid for tuberculous
      pleurisy.
AB  - BACKGROUND: A high concentration of hyaluronic acid in pleural fluid is
      suggestive of malignant mesothelioma. However, a relatively high concentration of
      hyaluronic acid was also seen in the pleural fluid of patients with benign
      inflammatory diseases. To show the utility of measuring hyaluronic acid levels in
      pleural fluid to diagnose tuberculous pleurisy, we compared the clinical features
      and levels of hyaluronic acid in the pleural fluid of patients with and without
      tuberculous pleurisy. METHODS: We enrolled 27 patients with infective pleurisy
      admitted at Teikyo University Hospital from January 2010 to December 2013. Ten
      patients were diagnosed with tuberculous pleurisy, and 17 with non-tuberculous
      pleurisy. We reviewed the clinical features and data of all 27 patients and
      compared the two groups. We analyzed and compared the concentration of hyaluronic
      acid and adenosine deaminase in their pleural fluid. RESULTS: Patients with
      tuberculous pleurisy tended to have significantly higher concentrations of
      hyaluronic acid and adenosine deaminase in their pleural fluid (tuberculous
      pleurisy patients vs. other infective pleurisy patients: hyaluronic acid (* 10(3)
      ng/mL); 42.9 +/- 23.3 vs. 16.8 +/- 17.9, P = 0.003, adenosine deaminase (IU/L);
      89.7 +/- 33.3 vs. 74.0 +/- 90.9, P = 0.032). Receiver operating characteristic
      analysis revealed no significant difference in the area under the curve of
      hyaluronic acid and adenosine deaminase volumes in pleural fluid, suggesting
      their equivalent value as major diagnostic tools for tuberculosis pleurisy.
      CONCLUSIONS: Hyaluronic acid concentration in pleural fluid can be a valuable
      tool for the diagnosis of tuberculous pleurisy.

PMID- 25368703
TI  - An atypical calcaneal fracture in a child: a literature review concerning the
      treatment.
AB  - Calcaneal fractures are considered uncommon accounting for 0.005-0.41% of all
      children fractures. Few reports concerning treatment are available. Most of these
      fractures are non-displaced/minimally displaced and are associated with a fall of
      less than 1 m. The aim of this case report was to discuss the diagnosis and
      treatment of a child calcaneal fracture, an atypical presentation despite the
      high energy mechanism of trauma. A 7-year-old child fell from a 5-m ladder with
      all his weight on his right heel. Significantly hind-foot reduced range of motion
      associated with a lateral/plantar calcaneal swelling and pain was found.
      Neurovascular examination and other parts of the body were normal. Radiograph
      showed an undisplaced calcaneal body fracture and computed tomography confirmed
      no subtalar joint involvement. A splint followed by plaster was applied. Weight
      bearing and deambulation were not allowed. After 4 weeks, no pain and limping was
      reported by the child's parents. Plaster was removed and radiograph showed
      fracture consolidation. Patient had no complaints of pain, no restrictions in
      range of motion and normal walking. Limping in children is a difficult complaint
      to assess. Differential diagnoses of a calcaneal fractures should be performed,
      even without a history of trauma or a history of trivial trauma. 

PMID- 25368702
TI  - Prognosis of hyponatremia in elderly patients with fragility fractures.
AB  - BACKGROUND: Hyponatremia (serum sodium < 135 mmol/L) is the commonest electrolyte
      imbalance encountered in clinical practice. It is associated with multiple poor
      clinical outcomes including increased length of hospital stay,
      institutionalization and mortality. Prevalence of hyponatremia is higher in frail
      patient groups, and elderly patients with fragility fractures (EPFF) are
      particularly susceptible. This study aimed to establish the impact of
      hyponatremia on total length of inpatient stay (TLOS), need for inpatient
      rehabilitation and mortality in EPFF. METHODS: Prospective observational study of
      consenting adults aged >= 65 years admitted with a fragility fracture to a
      university hospital between January 7, and April 4, 2013. Demographic and
      clinical data, length of hospital stay, discharge destination and any participant
      deaths were recorded. Prevalence of hyponatremia on admission and incidence of
      cases developing in hospital were reported. Basic demographic data and serum
      sodium results were included in multivariate linear regression models for TLOS.
      Difference in mortality rate and proportion of individuals discharged to
      inpatient rehabilitation between the hyponatremic and normonatremic group were
      tested using Chi-squared and Fisher's exact tests. Unadjusted odds ratios (ORs)
      and 95% confidence intervals (CIs) were also calculated. RESULTS: Of 212 cases,
      127 (60%) EPFF were recruited (mean age 79 years, 78% female). Of those not
      recruited, 66 had incapacity to consent and 19 refused participation. Thirty
      three cases of hyponatremia were identified; point prevalence on admission was
      13.4% and a further 12.6% developed hyponatremia during admission. There were no
      statistically significant differences in patient characteristics between the
      hyponatremic and normonatremic group. Hyponatremic participants had a 66.7%
      increased time from admission to surgery (P = 0.014) and a 51.5% increased length
      of index hospital stay (P = 0.006). Factors independently associated with
      increased TLOS were age (P = 0.03) and drop in sodium during admission (P <
      0.001). Mortality rate and proportion of participants discharged to inpatient
      rehabilitation were higher in the hyponatremic group (OR 4.2 (95% CI: 0.9 - 19.8)
      and 2.2 (95% CI: 0.9 - 5.1), respectively), but figures did not reach statistical
      significance. CONCLUSIONS: Hyponatremia is highly prevalent in EPFF, seen in
      33/127 cases (26%), and is associated with increased length of index hospital
      stay. Drop in serum sodium during admission was independently associated with
      increased TLOS.

PMID- 25368704
TI  - Spontaneous postpartum rupture of an intact uterus: a case report.
AB  - Rupture of uterus is an obstetrical complication characterized by a breach in the
      uterine wall and the overlying serosa. We report an unusual case of spontaneous
      rupture of an unscarred uterus in a 33-year-old woman, a day after her third
      successful vaginal delivery. A 33-year-old pregnant woman, gravid 3, para 3, was
      referred to our department at 39 gestational week because of rupture of
      membranes. Despite tocolysis administration, her pregnancy was delivered
      vaginally after 2 days, giving birth to a male neonate of 3,020 g with normal
      Apgar scores at first and fifth minute. Her uterus was intact and gynecological
      examination after delivery was normal without any potential signs or symptoms of
      pathology. However, the day following her labor, patient complained of left iliac
      fossa pain. Her blood tests revealed a CRP value at 27.6 mg/L, whereas the X-rays
      revealed an extensive impacted fecal mass in the colon. MRI revealed that the
      left lower myometrial part of the uterus was depicted abrupt, with simultaneous
      presence of hemorrhagic stuff. The decision of laparotomy was therefore made in
      order to further evaluate rupture of uterus and properly treat patient. And
      subtotal hysterectomy was performed. Postoperative follow-up period was not
      characterized by any complications and patient was finally discharged 4 days
      after hysterectomy. 

PMID- 25368705
TI  - Successful treatment of rectovaginal fistula complicating ulcerative colitis with
      infliximab: a case report and review of the literature.
AB  - Rectovaginal fistula is a rare complication of ulcerative colitis (UC) regardless
      of surgical history of rectum. Various surgical treatment modalities for the
      closure of rectovaginal fistula have been developed, but a radically curative
      therapy remains to be developed. Recently, infliximab, the chimeric anti-human
      tumor necrosis factor alpha (TNF-alpha) antibody, has been largely applied for
      the treatment of inflammatory bowel disease (IBD), and a few reports have shown
      its partial effectiveness in the management of rectovaginal fistulas associated
      with UC. In the present report, we describe the successful management of a
      rectovaginal fistula, following the stapled ileo-anal canal anastomosis in a UC
      patient, by administration of infliximab. The patient was a 40-year-old female,
      initially diagnosed as UC (total colitis type) at the age of 15. She received a
      restorative proctocolectomy at the age of 22, and developed a rectovaginal
      fistula at the eighth postoperative day. The surgical treatment of the fistula
      was repeated four times during the 10-year period, but it recurred in intervals
      ranging between 2 months and 5 years after the operation. The last recurrence
      occurred at the age of 32, but the surgical repair was considered difficult and a
      conservative management was indicated. At the age of 40, infusions of infliximab
      were started. Four weeks after the first infusion, drainage from the fistula was
      evidently reduced, and 2 weeks later, the fistula was completely closed.
      Thereafter, no recurrence of the fistula is observed, as confirmed by the
      abdominal magnetic resonance imaging (MRI) and the barium-enema study. From the
      present case, we concluded that infliximab may be an effective strategy for the
      management of fistulas associated with UC. 

PMID- 25368706
TI  - Young patient presenting acute coronary syndrome.
AB  - The clinical presentation of Kawasaki disease (KD) is variable and clinical
      implication among adults is rarely important but coronary involvement. Here we
      report a young patient showing recurrent acute coronary syndrome (ACS) who had a
      history of high-grade fever and conjunctivitis when he was little. Coronary
      angiography revealed aneurysmal coronary artery change in this patient. There is
      no particular consensus on guidelines for treatment for KD in case of coronary
      aneurysm causing ACS. In this case, we treated him medically without stent
      implantation successfully. 

PMID- 25368707
TI  - Immune reconstitution inflammatory syndrome mimicking progressive multifocal
      leucoencephalopathy in a multiple sclerosis patient treated with natalizumab: a
      case report and review of the literature.
AB  - Natalizumab (NTM) represents an effective drug for the treatment of relapsing
      remitting multiple sclerosis (RRMS). Progressive multifocal leucoencephalopathy
      (PML) is a potential life-threatening complication of NTM treatment. A close
      follow-up and MRI monitoring of patients under NTM are required to avoid such
      devastating complications. The case of a 47-year-old woman with RRMS (EDSS 1.5)
      treated with NTM for 44 months is reported. The patient had a relapse with mild
      cerebellar symptomatology and visual complaints. MRI revealed a new area of
      abnormal signal intensity in the subcortical white matter of the right parietal
      lobe with mild peripheral enhancement. Visual fields showed scotomata mostly of
      the left eye. NTM was discontinued. JC virus (JCV) polymerase chain reaction
      (PCR) in cerebrospinal fluid was negative. The patient received IV
      corticosteroids for 5 days and then monthly for 2 months with subsequent clinical
      and MRI improvement. On month 4, she presented with a new relapse with severe
      ataxia, mild behavioral change, increase of cerebellar symptoms and internuclear
      opthalmoplegia (EDSS 3.5). MRI showed reappearance of the right parietal lobe
      lesion, with decreased size and less pronounced contrast enhancement. A new 2-cm
      lesion was noted in the left cerebellar hemisphere with a speckled pattern of
      contrast enhancement. JCV PCR was negative and the patient was treated with IV
      corticosteroids. On month 12, she demonstrated clinical and MRI improvement.
      Although initially PML was highly suspected in this patient, the clinical and MRI
      findings were supportive of the presence of immune reconstitution inflammatory
      syndrome (IRIS). 

PMID- 25368708
TI  - [A cerebral metastasis revealed by chronic otomastoiditis].

PMID- 25368709
TI  - [Congenital bilateral entropion: report of a case].

PMID- 25368710
TI  - [The place of magnetic resonance imaging in lobular carcinoma of the breast].

PMID- 25368711
TI  - [The penile schwannoma: report of a case].

PMID- 25368712
TI  - [Muscle metastasis of an epidermoid carcinoma of the cervix: report of a case and
      review of the literature].

PMID- 25368713
TI  - [Aniridia and aphakia after trauma].

PMID- 25368714
TI  - Adverse drug reactions to antiretroviral therapy during the early art period at a
      tertiary hospital in Ghana.
AB  - INTRODUCTION: Antiretroviral therapy (ART) has reduced HIV morbidity and
      mortality worldwide but has many adverse effects. These adverse drug reactions
      (ADRs) lead to discontinuations, disease progression or treatment failure. We
      explored the types and risk factors for ADRs in a cohort starting ART in a
      teaching hospital in Accra, Ghana where the main regimens used were a combination
      of nucleotide and non nucleotide reverse transcriptase inhibitors. METHODS: A
      Cross-sectional retrospective study was conducted reviewing data of 2042 patients
      initiated on HAART from 2003 to 2007. Univariate analysis was done for the
      dependent and independent variables. Stepwise logistic regression procedures were
      used to model the effect of gender on the development of ADRs controlling for
      other variables like age, marital status, weight at baseline and CD4 at baseline.
      RESULTS: The period prevalence of ADRs was 9.4%. The two most common adverse
      reactions were anaemia and diarrhoea. Female sex was a statistically significant
      independent predictor of an adverse drug reaction (AOR: 1.66, p=0.01, CI: 1.16
      2.36). CD4 counts 250 cells/mm3 or more was significantly associated with the
      occurrence of an ADR. The occurrence of anaemia in females was statistically
      significant compared to males. CONCLUSION: Adverse drug reactions were less
      common than expected, anaemia was the commonest ADR. Female sex and high CD4
      counts>250 mm3 were predictors of ADRs whereas females were significantly more
      likely to develop anaemia than males. Recommendations were made for interventions
      to prevent and also mitigate the high levels of anaemia especially among women in
      the ART scale up.

PMID- 25368715
TI  - [Anorectal malignant tumors in the hospital environment in Ouagadougou:
      epidemiological and diagnostic aspects].

PMID- 25368717
TI  - Necrobiosis lipoidica-like cutaneous leishmaniasis.

PMID- 25368716
TI  - [Rare association of a pleomorphic adenoma and epithelial myoepithelial carcinoma
      of the parotid gland].

PMID- 25368718
TI  - Peri-partum cardiomyopathy in a pregnant woman at term revealed by acute
      pulmonary edema: what to do in front this catastrophic situation?
AB  - Peripartum cardiomyopathy is insufficient congestive heart occurring in the last
      month of pregnancy and 5 months after delivery, in the absence of preexisting
      heart disease and identified etiology. This heart disease is associated with
      echocardiography systolic dysfunction and left ventricular dilatation. Its
      incidence ranges from 1/3000 to 1/15000, depending on the region, including much
      higher in some African countries, it particularly concern women over 30 years,
      multiparous and multiple pregnancies. The pathogenesis remains unclear, the
      prognosis is closely related to the complete recovery of cardiac function. We
      report through the clinical case of a woman aged 33 years admitted to the ICU for
      acute pulmonary edema of sudden onset of a term pregnancy and what to do before
      this critical situation.

PMID- 25368719
TI  - Autopsy findings and pattern of mortality in Nigerian sickle cell disease
      patients.
AB  - INTRODUCTION: Sickle Cell Disease (SCD) has a high mortality rate in the
      environment where we practice. There is lack of contemporal autopsy studies
      describing causes of death among SCD patients at our centre. METHODS: This is a
      retrospective study of SCD patients who died between January 1991 and December
      2008 and that had autopsy examination to confirm the cause of death in a Nigerian
      teaching hospital. The clinical data, including the age, gender, Hb genotype, and
      the major autopsy findings and cause of death were obtained for each patient from
      the complete autopsy reports that included histopathological examination.
      Multiple causes of death were entertained. RESULTS: A total of 52 autopsies were
      performed. The mean age at death was 21.3 years (range, 1-47 years) and a
      male/female ratio of 1.3:1. HbS+C patients lived longer than HbS patients (21.0
      years Vs 24.0 years) and peak mortality was in the 2nd and 3rd decades of life.
      The commonest causes of death as a single entity or in combination included
      infections in 78% of cases, fatal thrombotic/embolic events (37%) making acute
      chest syndrome a leading cause of death. This was followed closely by anemia
      alone or in combination with acute sequestration crises in 31% of patients.
      CONCLUSION: Infections are the commonest causes of death in Nigerian SCD
      patients, efforts to reduce infection especially early in life through
      prophylaxis or vaccination will impact on the overall survival of these patients.

PMID- 25368720
TI  - [Retinal angioma of the Von Hippel-Lindau disease].

PMID- 25368721
TI  - Knowledge of tuberculosis management using directly observed treatment short
      course therapy among final year medical students in South Western Nigeria.
AB  - INTRODUCTION: Equipping medical graduates with the competence to manage
      tuberculosis is not just imperative but also urgent as the diseases have been
      consistently listed as one of the major causes of morbidity and mortality in
      Nigeria. However, there were no baseline studies done on knowledge of final year
      medical students on various aspects of TB diagnosis and management under directly
      observed treatment short course therapy (DOTS) which forms the basis of this
      study. METHODS: A total of 241 final year medical students from three medical
      colleges in Nigeria were interviewed. The questions assessed their knowledge
      about various modes of transmission, symptoms and management of tuberculosis
      under DOTS. RESULTS: More than half of the respondents (i.e. 69%) had poor
      knowledge on TB disease. Only 33.6% mentioned sputum smear as the best tool of
      diagnosing TB according to guideline. Poor knowledge was also exhibited when
      asked of various categories under DOTS treatment regimen, as 46.1% correctly
      mentioned cat 1 and 2. Minority 18.7% and 6.7% had complete knowledge of 6 months
      duration for new TB cases and 8 months for re-treatment cases respectively. Less
      than one tenth, i.e. 4.6% and 2.9% could correctly defined what is called a new
      TB case and re-treatment cases according to standard guideline. CONCLUSION: The
      study reveals gross inadequacies in TB knowledge and management practices among
      Nigerian final year medical students. There is urgent need for incorporation of
      National TB guideline into existing undergraduate medical education curriculum as
      well as students rotation through activities in DOTS clinic.

PMID- 25368722
TI  - [A neo of the vulva in an HIV seropositive patient: report of a case history].

PMID- 25368723
TI  - [Spinocerebellar ataxia type 7 (SCA) diagnosed by the appearance of the fundus].

PMID- 25368725
TI  - [Appendiceal mucocele: report of a case observed in Lubumbashi].

PMID- 25368724
TI  - Intravenous immunoglobulin vs plasma exchange in treatment of mechanically
      ventilated adults with Guillain-Barre syndrome.
AB  - INTRODUCTION: The aim of the study is to compare efficacy of IvIg versus PE in
      treatment of mechanically ventilation adults with GBS in intensive care unit.
      METHODS: It is a prospective, non randomized study, realized in a medical ICU
      from 2006 to 2010. We included all patients with GBS who required mechanical
      ventilation (MV). We defined two groups: group 1 (group treated by IvIg: 0.4
      g/kg/day for 5 days) and group 2 (group treated by PE: 4 PE during 10-14 days).
      We collected demographic characteristics, clinical and therapeutic aspects and
      outcome. STATISTICAL ANALYSIS USED: The quantitative variables are expressed on
      mean +/- standard derivation and compared by Student test. The statistic analysis
      has been based on SPSS for windows. P<0.05 is considered as significant. RESULTS:
      Forty-one patients (21 in group 1 and 20 in group 2) were enrolled. The mean age
      was 37.4+/-9.2 years, with a masculine predominance (75.4%). Electromyogram in
      all patients found acute inflammatory demyelinating polyradiculoneuropathy in
      80.5% of patients. The mean length of hospitalization was 45.3+/-9.2 days. The
      length of hospitalization of the IvIg group is less long than PE group (p=0.03).
      The weaning of the MV was more precocious in IvIg group than PE group (p=0.01).
      Also, the beginning of motility recuperation was precocious at IvIg group than PE
      group (p=0.04). CONCLUSION: Our work reveals a meaningful difference for the MV
      weaning and precocious recovery in IvIg group compared to PE group.

PMID- 25368727
TI  - [Enormous Buschke Lowenstein tumor: report of a case history].

PMID- 25368726
TI  - Lipid patterns, alcohol intake and BMI of adult Nigerians in a sub-urban slum in
      Enugu, Nigeria.
AB  - INTRODUCTION: Demonstration of cardiovascular disease (CVD) markers in healthy
      subjects with normal blood chemistry tests underscores the need to study social
      determinants of risk factors to aid primary prevention worldwide; particularly in
      slums which harbor nearly 80% of rural to urban migrants in the epidemiologically
      transiting Africa where CVDs were previously unknown. The objective of this study
      was to assess lipids in relationship to alcohol consumption and BMI in a Nigerian
      slum. METHODS: Cross sectional community based prevalent study involving 191
      apparently healthy inhabitants aged 18-85 years recruited by convenient sampling.
      Heights, weights and BMIs were measured/ calculated, venous blood samples
      collected and lipid analysis done procedurally. Excel 13 and SPSS statistical
      soft ware were used for analysis and chart representation. RESULTS: THEIR MEAN
      PARAMETERS WERE: Age (43.87+/-1.62 years), triglycerides (TG; 1.20+/-0.08
      mmol/L), total Cholesterol (TC; 4.54+/-1.70 mmol/L), low density lipoprotein
      cholesterol (LDLC; 3.69+/-1.69 mmol/L), high density lipoprotein cholesterol
      (HDLC; 0.61+/-0.24 mmol/L), RPI (7.12+/-5.24), body mass index (BMI; 25.08+/-5.18
      Kg/M2). TG and HDLC values were lowest in obese non alcohol drinkers while all
      other lipid parameters increased with BMI in both drinkers and non drinkers. Low
      HDLC prevalence was lowest in obese alcohol drinkers and highest (100%) in their
      non drinking counterparts. Having favourable HDLC was highest in daily alcohol
      consumers. No weekly drinker (0%) had favourable HDLC. CONCLUSION: Ignorance,
      poor nutritional and health education may be major factors in the strategic
      challenge posed by the emergence of non communicable diseases in Africans.

PMID- 25368728
TI  - [Transverse leuconychia induced by manicure: is there a contribution from
      dermoscopy?].

PMID- 25368729
TI  - Chronic rhinosinusitis: correlation of symptoms with computed tomography scan
      findings.
AB  - INTRODUCTION: Symptomatology, nasal endoscopy and Computerised Tomographic (CT)
      scan have been used to diagnose chronic rhinosinusitis. The value of disease
      severity score in the assessment of chronic rhinosinusitis has not been well
      investigated. Hence, this study aims to correlate the pre-operative symptom
      severity score as well as overall disease severity score of patients with chronic
      rhinosinusitis with CT scan scores. METHODS: This is a prospective study of 60
      patients diagnosed clinically with chronic rhinosinusitis. Each patients
      ubjectively assessed his/her presenting symptoms and severity of disease on a
      visual analogue scale. The patients had CT scan of the paranasal sinuses which
      were graded and scored using Lund-Mackay grading system. The correlation study
      between severity of symptoms/disease severity and CT scores was performed. The
      level of statistical significance was considered at p<0.05 and confidence
      interval at 95%. RESULTS: All patients had more than one symptom with mean
      symptom severity scores highest for nasal discharge and nasal obstruction. There
      was a significant correlation between CT scores and nasal discharge (r=-0.132;
      p=0.03)and nasal obstruction (r=0.193; p=0.049). No correlation with other
      symptoms. There was no correlation between the overall disease severity scores
      and the Lund-Mackay CT scores (r=0.195; p=0.6). CONCLUSION: This study showed
      that CT scan scores can help clinicians to predict severity of symptom for nasal
      obstruction and discharge but not for other symptoms of chronic rhinosinusitis.
      However, there was no association of CT score with the overall disease severity
      score.

PMID- 25368730
TI  - [Tracheal migration of a tracheotomy tube: rare complication].

PMID- 25368731
TI  - Mean platelet volume and platelet counts in type 2 diabetes: mellitus on
      treatment and non-diabetic mellitus controls in Lagos, Nigeria.
AB  - INTRODUCTION: The Mean platelet volume and platelet counts are indicators of
      thrombotic potentials, and risk factors for microvascular complications in
      diabetics. This study aimed to establish variations in platelet counts and mean
      platelet volume in type 2 diabetic patients on treatment and non-diabetic
      controls. METHODS: This was an unmatched case-control study involving 200
      participants consisting of 100 diabetics and 100 non-diabetic controls. Four and
      half milliliters of blood was collected from diabetics and non diabetic controls
      into EDTA anticoagulant tubes. Full blood count was performed using the Sysmex KN
      21N, (manufactured by Sysmex corporation Kobe, Japan) a three- part auto analyzer
      able to run 19 parameters per sample including platelet counts and mean platelet
      volume. RESULTS: The mean fasting blood sugar for the diabetics was 147.85+/
      72.54 mg/dl and the controls 95.20+/-30.10 mg/dl. The mean platelet count for the
      diabetics was 235.29+/-76.81*10(9)/L and controls, 211.32+/-66.44*10(9)/L. The
      mean platelet volume, for the diabetics was 8.69+/-0.67 fl and the controls,
      8.91+/-0.80 fl. There was a statistically significant difference in platelet
      counts of diabetics and healthy controls p =0.038 while none existed between the
      mean platelet volume in diabetics and healthy controls p=0.593. CONCLUSION: This
      study revealed a higher mean platelet count for diabetics on treatment than for
      non diabetic controls while mean platelet volume was lower in cases than
      controls. However, both parameters in diabetics on treatment were within the
      normal reference range for healthy individuals.

PMID- 25368732
TI  - What prevent women for a sustainable use of maternal care in two medical
      districts of Burkina Faso? A qualitative study.
AB  - INTRODUCTION: Skilled attendance is one of the major strategies to curtail
      maternal mortality, specifically in developing countries. Despite the low level
      of equipment, it is only in health facilities that skilled care are provided
      during pregnancy and childbirth; but there are some barriers which prevent women
      to use health facilities for good care. METHODS: This study was carried out in
      Ouargaye where a skilled care initiative was implemented by Family care
      International with the aim to increase the skilled attendance at delivery and
      Diapaga, the control district. Thirty (30) In-depth interviews, 8 Focus group
      discussions and 6 non participant observations were carried out. Participants
      were women from 15-49 years. All the interviews were tape-recorded, transcribed
      and analysed line by line. NVIVO was used to manage the interviews. RESULTS: Four
      types of barriers have been described by women; 1) the cultural barriers concern
      the low status of women in the two districts and some traditional beliefs which
      mean that women can not always decide to use health facility by themselves. 2)
      The geographical barrier is about the distance to reach health facility and the
      lack of transport means. 3) The financial barrier to pay care and drugs. 4) Bad
      organization of care and poor quality of care provided to women. CONCLUSION: To
      minimize the risk of complications during pregnancy and childbirth, it is
      important that women use health facilities. The barriers described by women are
      not insurmountable but needed to be integrated in a global comprehensive health
      policy.

PMID- 25368733
TI  - [Thick cutaneous melanoma: mortality factors and occurrence of metastases].

PMID- 25368734
TI  - [Echocardiographic aspects of sickle cell disease in Guadeloupe].

PMID- 25368737
TI  - [The giant congenital nevus].

PMID- 25368736
TI  - [Congenital Plasmodium falciparum malaria: epidemiological, clinical, biological,
      therapeutic and prognostic aspects in Ouagadougou, Burkina Faso].

PMID- 25368735
TI  - Treatment for sickle cell disease in Africa: should we invest in haematopoietic
      stem cell transplantation?

PMID- 25368738
TI  - [Digital necrosis of a diabetic on hemodialysis].

PMID- 25368739
TI  - Factors associated with HIV-status disclosure to HIV-infected children receiving
      care at Kilimanjaro Christian Medical Centre in Moshi, Tanzania.
AB  - INTRODUCTION: With the introduction of antiretroviral drugs HIV-infected children
      live longer. Disclosure of HIV diagnosis is increasingly an important and
      inevitable issue. Both healthcare providers and caregivers face challenges of
      disclosure to children. The objective of the study was to explore factors
      associated with HIV-status disclosure to HIV-infected children receiving care at
      Kilimanjaro Christian Medical Centre (KCMC). METHODS: A cross-sectional hospital
      based study was conducted from October 2011 to April 2012. Study population
      included HIV-infected children aged 5 to 14 years, their caregivers and
      healthcare providers. Structured questionnaires were used to collect information.
      Children were asked the reason for hospital visits. Outcome of interest was HIV
      disclosure status. Data was processed and analysed using SPSS version 16.0.
      Multivariate logistic regression at 5% margin error was used to account for
      confounders. RESULTS: A total of 211 children were enrolled with mean age of 9.7
      (SD+/-2.6; range 5-14) years. Only 47 (22.3%) children knew their HIV-status. The
      mean age of disclosure was 10.6 years. Most of disclosed children were aged above
      10 years (p). CONCLUSION: Most of children were not disclosed. Ages, self
      medication, getting other support and parents/caregivers prior discussion were
      strong predictors of disclosure status.

PMID- 25368740
TI  - The surgical relevance of the anatomic position of the extraosseous mental nerve
      in a Kenyan population.
AB  - INTRODUCTION: Precise location of the mental nerve is important in implant
      surgery, administration of mental nerve block anaesthesia, and for osteotomy
      procedures. The position is known to show inter-population differences but data
      from sub-saharan region is scarce. METHODS: The point of emergence of 64 nerves
      was studied and data analyzed with Microsoft Excel 2010 and differences in side
      means compared using the paired one tailed student's t test. RESULTS: The
      location of left mental nerve was 2.85 (+/-0.38) cm, 1.42 (+/-0.33) cm, 1.77 (+/
      0.46) cm while the right was 2.91(+/-0.47) cm, 1.38 (+/-0.3.1) cm, 1.71 (+/-0.46)
      cm from the mental symphysis, inferior border of mandible and cemento-enamel
      junction respectively. The differences in position between the right and left
      sides were not statistically significant (p<0.05 CI: 95%). It emerged inferior to
      but in line with the 2nd premolar in 57.8% of the cases, 2nd premolar-1st molar
      (25%) and inter-premolar junction (9.4%). Unique to this study, was the location
      of the MN at the canine (3.1%), and 1st molar (4.7%) positions. CONCLUSION: The
      aberrant position of the mental nerve seen in 42%, is an important consideration
      for tooth implants and placement of mandibular reconstruction plates.

PMID- 25368741
TI  - Genetic susceptibility of gastroduodenal disease in ethnic and regional
      diversity.

PMID- 25368742
TI  - Once in a blue moon, the bone marrow aspiration and biopsy has clinical impact
      for gastric mucosa-associated lymphoid tissue lymphoma.

PMID- 25368743
TI  - Ribonucleotide reductase subunit M2 can be new molecular target and prognostic
      biomarker of hepatocellular carcinoma.

PMID- 25368744
TI  - Pathogenesis and management of serrated polyps: current status and future
      directions.
AB  - Hyperplastic or serrated polyps were once believed to have little to no clinical
      significance. A subset of these polyps are now considered to be precursors to
      colorectal cancers (CRC) in the serrated pathway that may account for at least
      15% of all tumors. The serrated pathway is distinct from the two other CRC
      pathways and involves an epigenetic hypermethylation mechanism of CpG islands
      within promoter regions of tumor suppressor genes. This process results in the
      formation of CpG island methylator phenotype tumors. Serrated polyps are divided
      into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and
      traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential
      for dysplasia and subsequent malignant transformation. The SSA/Ps are more common
      and are more likely to be flat than TSAs. Their flat morphology may make them
      difficult to detect and thus explain the variation in detection rates among
      endoscopists. Challenges for endoscopists also include the difficulty in
      pathological interpretation as well surveillance of these lesions. Furthermore,
      serrated polyps may be inadequately resected by endoscopists. Thus, it is not
      surprising that the serrated pathway has been linked with interval cancers. This
      review will provide the physician or clinician with the knowledge to manage
      patients with serrated polyps. 

PMID- 25368745
TI  - An overview of eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal
      disease affecting both children and adults. The condition is characterized by an
      eosinophilic infiltration of the esophageal epithelium. Symptoms of esophageal
      dysfunction include dysphagia, food impaction and symptoms mimicking
      gastroesophageal reflux disease. Endoscopic examination typically reveals mucosal
      fragility, ring or corrugated mucosa, longitudinal furrows, whitish plaques or a
      small caliber esophagus. Histologic findings of >15 eosinophils per high-power
      field is the diagnostic hallmark of EoE. An elimination diet, topical
      corticosteroids or endoscopic dilation for fibrostenotic disease serve as
      effective therapeutic option. 

PMID- 25368746
TI  - Current status of endoscopic papillectomy for ampullary tumors.
AB  - Detection of tumors of the ampulla of Vater, including ampullary adenoma, has
      been improved by routine screening endoscopic procedures and imaging modalities.
      Endoscopic resection by endoscopic papillectomy is rapidly replacing classic
      surgical resection and is a less invasive procedure. Endoscopic resection can
      have a role not only in the final histopathologic diagnosis but also as a
      definite therapeutic option. However, the indications for endoscopic resection
      are not fully established, and endoscopic procedures are not standardized.
      Significant complications, including severe pancreatitis, intractable bleeding
      and duodenal perforation, are rare but can occur, especially in less experienced
      hands. Severe pancreatitis is the most feared complication, but it can be
      prevented by pancreatic duct stent insertion in most cases. However, in some
      cases, pancreatic stenting can be challenging after resection. Incomplete
      resections are sometimes performed to avoid complications. Endoscopic
      surveillance is also important for identifying and managing remnant adenomatous
      tissue or recurrent lesions. Further technical development is needed to expand
      the indications for this procedure, minimize complications and ensure a high
      success rate. 

PMID- 25368747
TI  - The efficacy of moxifloxacin-containing triple therapy after standard triple,
      sequential, or concomitant therapy failure for Helicobacter pylori eradication in
      Korea.
AB  - BACKGROUND/AIMS: Retreatment after initial treatment failure for Helicobacter
      pylori is very challenging. The purpose of this study was to evaluate the
      efficacies of moxifloxacin-containing triple and bismuth-containing quadruple
      therapy. METHODS: A total of 151 patients, who failed initial H. pylori
      treatment, were included in this retrospective cohort study. The initial regimens
      were standard triple, sequential, or concomitant therapy, and the efficacies of
      the two following second-line treatments were evaluated: 7-day moxifloxacin
      containing triple therapy (rabeprazole 20 mg twice a day, amoxicillin 1,000 mg
      twice a day, and moxifloxacin 400 mg once daily) and 7-day bismuth-containing
      quadruple therapy (rabeprazole 20 mg twice a day, tetracycline 500 mg 4 times a
      day, metronidazole 500 mg 3 times a day, and tripotassium dicitrate bismuthate
      300 mg 4 times a day). RESULTS: The overall eradication rates after moxifloxacin
      containing triple therapy and bismuth-containing quadruple therapy were 69/110
      (62.7%) and 32/41 (78%), respectively. Comparison of the two regimens was
      performed in the patients who failed standard triple therapy, and the results
      revealed eradication rates of 14/28 (50%) and 32/41 (78%), respectively
      (p=0.015). The frequency of noncompliance was not different between the two
      groups, and there were fewer adverse effects in the moxifloxacin-containing
      triple therapy group (2.8% vs 7.3%, p=0.204 and 25.7% vs 43.9%, p=0.031,
      respectively). CONCLUSIONS: Moxifloxacin-containing triple therapy, a recommended
      second-line treatment for initial concomitant or sequential therapy failure, had
      insufficient efficacy.

PMID- 25368748
TI  - Long-term outcome after endoscopic submucosal dissection in patients with
      superficial esophageal squamous cell carcinoma: a single-center study.
AB  - BACKGROUND/AIMS: Superficial esophageal squamous cell carcinoma (SESCC) is being
      increasingly detected during screening endoscopy. Endoscopic submucosal
      dissection (ESD) allows for en bloc and histologically complete resection of
      lesions. This study assessed the technical feasibility and long-term outcomes of
      ESD for SESCCs. METHODS: Between January 2005 and August 2012, 27 patients with
      28 SESCCs underwent ESD at Pusan National University Hospital. The en bloc and
      pathologically complete resection rates, complication (perforation and bleeding)
      rate, incidence of esophageal stricture after ESD, and overall and disease
      specific survival rates were evaluated. RESULTS: The en bloc and pathologically
      complete resection rates were 93% and 83%, respectively. No significant bleeding
      occurred, and perforation with mediastinal emphysema was observed in two patients
      (7%). Post-ESD stricture occurred in two patients (7%) who had mucosal defects
      involving more than three-fourths of the esophageal circumference. During a mean
      follow-up of 23 months, local tumor recurrence was seen in two of four lesions
      with pathologically incomplete resection; one was treated by re-ESD, and the
      other was treated by surgical esophagectomy. The 5-year overall and disease
      specific survival rates were 84% and 100%, respectively. CONCLUSIONS: ESD seems
      to be a feasible, effective curative treatment for SESCCs. All patients should be
      closely followed after ESD.

PMID- 25368749
TI  - The feasibility of using simulated targets in the stomachs of live pigs for full
      endoscopic submucosal dissection training.
AB  - BACKGROUND/AIMS: In endoscopic submucosal dissection (ESD) training, only a flat
      target lesion can usually be simulated in the normal mucosa. This study aimed to
      evaluate the feasibility of simulated targets in the stomachs of live pigs for
      complete training. METHODS: Six trained endoscopists with hands-on experience
      with ex vivo, isolated pig stomachs were enrolled in this pilot study. An
      endoscopic banding device was used to create a polyp that was snared, leaving an
      ulcerated lesion. This simulated target model was used to perform ESD in pigs.
      The en bloc resection rate, procedure time, complications, quality of resection,
      and participants' opinions on the simulated targets were compared with the
      conventional model. RESULTS: En bloc resections were achieved in all six
      simulated targets and six conventional models. The mean size of the resected
      specimens was 32.2 mm (range, 20 to 39 mm) in the simulated target group and 23.5
      mm (range, 11 to 40 mm) in the conventional group. The target model had a high
      quality of resection and had a high satisfaction rate for margin identification
      and correct peripheral marking. CONCLUSIONS: Good identification of the lesion
      and ease of periphery marking in the target model may improve resection quality.

PMID- 25368750
TI  - Importance of the time interval between bowel preparation and colonoscopy in
      determining the quality of bowel preparation for full-dose polyethylene glycol
      preparation.
AB  - BACKGROUND/AIMS: The quality of bowel preparation (QBP) is the important factor
      in performing a successful colonoscopy. Several factors influencing QBP have been
      reported; however, some factors, such as the optimal preparation-to-colonoscopy
      time interval, remain controversial. This study aimed to determine the factors
      influencing QBP and the optimal time interval for full-dose polyethylene glycol
      (PEG) preparation. METHODS: A total of 165 patients who underwent colonoscopy
      from June 2012 to August 2012 were prospectively evaluated. The QBP was assessed
      using the Ottawa Bowel Preparation Scale (Ottawa) score according to several
      factors influencing the QBP were analyzed. RESULTS: Colonoscopies with a time
      interval of 5 to 6 hours had the best Ottawa score in all parts of the colon.
      Patients with time intervals of 6 hours or less had the better QBP than those
      with time intervals of more than 6 hours (p=0.046). In the multivariate analysis,
      the time interval (odds ratio, 1.897; 95% confidence interval, 1.006 to 3.577;
      p=0.048) was the only significant contributor to a satisfactory bowel
      preparation. CONCLUSIONS: The optimal time was 5 to 6 hours for the full-dose PEG
      method, and the time interval was the only significant contributor to a
      satisfactory bowel preparation.

PMID- 25368751
TI  - Investigation of -308G>A and -1031T>C polymorphisms in the TNFA promoter region
      in Polish peptic ulcer patients.
AB  - BACKGROUND/AIMS: Tumor necrosis factor alpha (TNF-alpha) encoded by TNFA is a key
      mediator in inflammation, a precursor condition for peptic ulceration. Promoter
      polymorphisms of TNFA that influence its transcriptional activity and TNF-alpha
      production are known. TNFA-308G>A (rs1800629) and TNFA-1031T>C (rs1799964), which
      are responsible for increased TNFA transcription, could influence the risk of
      peptic ulceration. This study aimed to investigate these polymorphisms and to
      evaluate their association with peptic ulcer disease and Helicobacter pylori
      infection in the Polish population. METHODS: Gastric mucosa specimens obtained
      from 177 Polish peptic ulcer patients were used to conduct rapid urease tests and
      to assess the investigated polymorphisms by polymerase chain reaction-restriction
      fragment length polymorphism. Genotyping data were compared with the results
      obtained from healthy individuals of Polish origin. RESULTS: There were no
      significant differences in genotype and allele frequency of the investigated
      polymorphisms between peptic ulcer patients and healthy individuals. No
      associations between the frequencies of particular genotypes and alleles for both
      single-nucleotide polymorphisms (SNPs) and the presence of H. pylori infection in
      peptic ulcer patients and in subgroups of men and women with peptic ulcer disease
      were found. CONCLUSIONS: The investigated SNPs are not risk factors for either
      peptic ulcer or H. pylori infection development in the Polish population. The
      results require verification in a larger cohort.

PMID- 25368752
TI  - Limited role of bone marrow aspiration and biopsy in the initial staging work-up
      of gastric mucosa-associated lymphoid tissue lymphoma in Korea.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the frequency of
      disseminated gastric mucosa-associated lymphoid tissue (MALT) lymphoma and the
      role of bone marrow study in the initial staging work-up. METHODS: A total of 194
      patients with gastric MALT lymphoma was enrolled. The incidence of disseminated
      disease was evaluated in the initial staging work-up. The demographic data and
      tumor characteristics were compared according to Helicobacter pylori infection
      status. RESULTS: Localized disease of Lugano stage I accounted for 97.4% of the
      enrolled cases. Abdominal computed tomography revealed abdominal lymph node
      metastasis in five patients (2.6%). Bone marrow (BM) involvement was found in
      only one patient without H. pylori infection (0.5%). No patient showed positive
      findings on chest computed tomography or positron emission tomography. H. pylori
      negative cases showed a significantly higher frequency of advanced-stage disease
      than H. pylori-positive cases (10.0% vs 0.6%). In patients achieving complete
      remission, no extragastric recurrence occurred during follow-up. CONCLUSIONS: The
      incidence of disseminated disease, including BM involvement, was very low in
      Korean gastric MALT lymphoma patients. It might be beneficial to perform BM
      aspiration and biopsy as a part of staging work-up only in patients with risk
      factors for advanced disease such as H. pylori negativity.

PMID- 25368753
TI  - Long-term outcomes of cytomegalovirus reactivation in patients with moderate to
      severe ulcerative colitis: a multicenter study.
AB  - BACKGROUND/AIMS: Cytomegalovirus (CMV) reactivations are frequently observed in
      patients with active ulcerative colitis (UC), and ganciclovir therapy is
      effective in patients with steroid-refractory UC. This study aimed to determine
      the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy
      of ganciclovir treatment. METHODS: This retrospective multicenter study included
      a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV
      reactivation at the time of their initial UC flare. Colectomy, disease relapse,
      and the recurrence rate of CMV reactivation were investigated. RESULTS: The mean
      duration of follow-up for the 72 patients was 43.16+/-19.78 months (range, 1 to
      67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up
      rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of
      the 11 patients who were successfully treated with ganciclovir in the initial
      treatment, three patients (27.3%) experienced CMV reactivation, and six patients
      (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid
      dependent state. CONCLUSIONS: The patients who had CMV-reactivated UC showed poor
      outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir
      therapy was marginal. Careful assessment is necessary for patients who exhibit
      evidence of CMV reactivation.

PMID- 25368754
TI  - High expression of ribonucleotide reductase subunit M2 correlates with poor
      prognosis of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Ribonucleotide reductase subunit M2 (RRM2) catalyzes the
      production of deoxynucleotide triphosphates, which are necessary for DNA
      synthesis. RRM2 has been reported to play an active role in tumor progression,
      and elevated RRM2 levels have been correlated with poor prognosis for colorectal
      cancer patients. This study aimed to elucidate the prognostic significance of
      RRM2 protein expression in hepatocellular carcinoma after surgery. METHODS: RRM2
      protein expression was evaluated using immunohistochemistry in tumor tissues from
      259 hepatocellular carcinoma patients who underwent curative hepatectomy.
      RESULTS: High RRM2 expression was observed in 210 of 259 patients (81.1%) with
      hepatocellular carcinomas. High RRM2 expression was significantly associated with
      viral etiology (p=0.035) and liver cirrhosis (p=0.036). High RRM2 expression was
      correlated with early recurrence (p=0.004) but not with late recurrence
      (p=0.144). Logistic regression analysis revealed that high RRM2 expression
      (p=0.040) and intrahepatic metastasis (p<0.001) were independent predictors of
      early recurrence. High RRM2 expression unfavorably influenced both shorter
      recurrence-free survival (p=0.011) and shorter disease-specific survival
      (p=0.002) and was an independent predictor of shorter disease-specific survival
      (p=0.008). CONCLUSIONS: High RRM2 protein expression might be a useful marker for
      predicting early recurrence and may be a marker for poor prognosis of
      hepatocellular carcinoma after curative hepatectomy.

PMID- 25368755
TI  - Triple-tissue sampling during endoscopic retrograde cholangiopancreatography
      increases the overall diagnostic sensitivity for cholangiocarcinoma.
AB  - BACKGROUND/AIMS: There are several methods for obtaining tissue samples to
      diagnose malignant biliary strictures during endoscopic retrograde
      cholangiopancreatography (ERCP). However, each method has only limited
      sensitivity. This study aimed to evaluate the diagnostic accuracy of a combined
      triple-tissue sampling (TTS) method (on-site bile aspiration cytology, brush
      cytology, and forceps biopsy). METHODS: We retrospectively reviewed 168 patients
      with suspicious malignant biliary strictures who underwent double-tissue sampling
      (DTS; n=121) or TTS (n=47) via ERCP at our institution from 2004 to 2011.
      RESULTS: Among the 168 patients reviewed, 117 patients (69.6%) were eventually
      diagnosed with malignancies. The diagnostic sensitivity for cancer was
      significantly higher in the TTS group than the DTS group (85.0% vs 64.9%,
      respectively; p=0.022). Furthermore, the combination of brush cytology and
      forceps biopsy was superior to the other method combinations in the DTS group.
      With respect to cancer type (cholangiocarcinoma vs noncholangiocarcinoma),
      interestingly, the diagnostic sensitivity was higher for cholangiocarcinoma in
      the TTS group than the DTS group (100% vs 69.4%, respectively; p<0.001) but not
      for the non-cholangiocarcinoma patients (57.1% vs 57.1%, respectively).
      CONCLUSIONS: TTS can provide an improved diagnostic accuracy in suspicious
      malignant biliary strictures, particularly for cholangiocarcinoma.

PMID- 25368756
TI  - Endoscopic retrograde cholangiopancreatography in patients with previous acute
      coronary syndrome.
AB  - BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is
      considered a high-risk procedure in patients with previous acute coronary
      syndrome (ACS); however, clinical studies are rare in the literature. The aim of
      this study was to investigate the safety and efficacy of ERCP in patients with
      previous ACS. METHODS: We retrospectively reviewed the medical records of
      patients with previous ACS who underwent ERCP between January 2007 and August
      2012. The clinical characteristics, ERCP diagnoses, treatment results, and
      complications were analyzed. RESULTS: Fifty patients underwent ERCP an average of
      41.6 months after ACS. The most common indication for ERCP was calculous
      cholangitis. After deep biliary cannulation, endoscopic sphincterotomy, biliary
      stone removal and endoscopic biliary drainage were successfully performed.
      Immediate postsphincterotomy bleeding occurred in seven patients, which was
      successfully controlled using endoscopic therapy. Elevation of cardiac troponin I
      levels were observed in three patients (6%) before ERCP, and all of these
      patients were diagnosed with pancreatobiliary disease combined with recurrent
      ACS, which was treated with coronary artery stent insertion (n=2) and balloon
      angioplasty (n=1). CONCLUSIONS: Therapeutic ERCP is effective and safe in
      patients with previous ACS. Cardiac troponin I elevation should be considered a
      warning sign for recurrent ACS in patients who undergo ERCP.

PMID- 25368757
TI  - Contrast-enhanced ultrasound defines vascularization pattern of hamartomatous
      colonic polyps in Peutz-Jeghers syndrome.
AB  - The hamartomatous polyps in Peutz-Jeghers syndrome may have malignant potential.
      To differentiate between hamartomatous and adenomas polyps, vascular
      characterization can be assessed using noninvasive procedures, such as contrast
      enhanced ultrasound (CEUS). The neo-angiogenic characteristics of colorectal
      adenomas and carcinomas are expressed as an anarchic vascular pattern observed on
      CEUS. Using CEUS in a patient with Peutz-Jeghers syndrome, we describe for the
      first time the vascularization of a hamartomatous colonic polyp that exhibits a
      hierarchy branching pattern. 

PMID- 25368759
TI  - Preliminary study of neurocognitive dysfunction in adult moyamoya disease and
      improvement after superficial temporal artery-middle cerebral artery bypass.
AB  - OBJECTIVE: Moyamoya disease (MMD) is a chronic cerebrovascular occlusive disease
      of unknown etiology. In addition, the neurocognitive impairment of adults with
      MMD is infrequently reported and, to date, has not been well described. We
      attempted to determine both the neurocognitive profile of adult moyamoya disease
      and whether a superficial temporal artery-middle cerebral artery (STA-MCA)
      anastomosis can improve the neurocognitive impairment in exhibiting hemodynamic
      disturbance without stroke. METHODS: From September 2010 through November 2012,
      12 patients with angiographically diagnosed MMD underwent STA-MCA anastomosis for
      hemodynamic impairment. Patients with hypoperfusion and impaired cerebrovascular
      reserve (CVR) capacity but without evidence of ischemic stroke underwent a
      cognitive function test, the Seoul Neuropsychological Screening Battery (SNSB).
      Five patients agreed to undergo a follow-up SNSB test. Data from preoperative and
      postoperative neurocognitive function tests were compared and analyzed. RESULTS:
      Five of 12 patients were enrolled. The median age was 45 years (range, 24-55
      years). A comparison of preoperative to postoperative status of SNSB, memory
      domain, especially delayed recall showed significant improvement. Although most
      of the domains showed improvement after surgery, the results were not
      statistically significant. CONCLUSION: In our preliminary study, large
      proportions of adult patients with MMD demonstrate disruption of cognitive
      function. This suggests the possibility of chronic hypoperfusion as a primary
      cause of the neurocognitive impairment. When preoperative and postoperative
      status of cognitive function was compared, memory domain showed remarkable
      improvement. Although further study is needed, neurocognitive impairment may be
      an indication for earlier intervention with reperfusion procedures that can
      improve cognitive function.

PMID- 25368758
TI  - Clinical practice guidelines for the medical and surgical management of primary
      intracerebral hemorrhage in Korea.
AB  - The purpose of this clinical practice guideline (CPG) is to provide current and
      comprehensive recommendations for the medical and surgical management of primary
      intracerebral hemorrhage (ICH). Since the release of the first Korean CPGs for
      stroke, evidence has been accumulated in the management of ICH, such as
      intracranial pressure control and minimally invasive surgery, and it needs to be
      reflected in the updated version. The Quality Control Committee at the Korean
      Society of cerebrovascular Surgeons and the Writing Group at the Clinical
      Research Center for Stroke (CRCS) systematically reviewed relevant literature and
      major published guidelines between June 2007 and June 2013. Based on the
      published evidence, recommendations were synthesized, and the level of evidence
      and the grade of the recommendation were determined using the methods adapted
      from CRCS. A draft guideline was scrutinized by expert peer reviewers and also
      discussed at an expert consensus meeting until final agreement was achieved. CPGs
      based on scientific evidence are presented for the medical and surgical
      management of patients presenting with primary ICH. This CPG describes the
      current pertinent recommendations and suggests Korean recommendations for the
      medical and surgical management of a patient with primary ICH. 

PMID- 25368760
TI  - Clinical features and treatment outcome of chordoid meningiomas in a single
      institute.
AB  - OBJECTIVE: Meningioma is the second most common primary central nervous system
      neoplasm. In contrast, chordoid meningioma is rare; due to the paucity of cases,
      little is known about its clinical features or treatment outcomes. The objectives
      of this study were to describe the clinical characteristics and outcomes for
      patients with chordoid meningioma. METHODS: In total, 16 patients, with newly
      diagnosed chordoid meningioma who underwent surgical excision between 1999 and
      2012 were included. We retrospectively evaluated the medical records,
      radiological findings, and pathological findings. The median follow-up period was
      56.5 (range, 3-170) months. The MIB-1 labeling index ranged from 1 to 26.60%
      (median, 5.04). RESULTS: Simpson grade I, II, and III resections were performed
      in four, nine, and three patients, respectively. The overall recurrence rate was
      37.5%. Overall progression-free survival (PFS) after resection was 94.7 months
      (95% CI=62.9-126.6). Of the 4 patients with Simpson grade I resection, recurrence
      occurred in one patient. Among the Simpson grade II and III resection groups,
      eight patients underwent adjuvant radiation therapy and they showed significantly
      longer PFS (121 months, 95% CI=82.1-159.9) than the patients who underwent
      surgery alone (40.5 months, 95% CI=9.6-71.3) by the log-rank test (p<0.05).
      CONCLUSION: Chordoid meningiomas are difficult to manage and have a high rate of
      recurrence. Complete resection of the tumor is a key determinant of better
      outcomes. Adjuvant radiation therapy is recommended, eparticulary when Simpson
      grade I resection was not achieved.

PMID- 25368761
TI  - Extent of disc degeneration after single-level cervical anterior
      microforaminotomy analyzed with long-term radiological data.
AB  - OBJECTIVE: To prove the extents and details of cervical degeneration after
      anterior microforaminotomy (AMF) with 6-years follow-up. METHODS: A retrospective
      study of 24 patients, underwent single-level AMF, was performed. Clinical and
      radiologic data were analyzed with office charts, questionaires, and picture
      achieving and communication system images. RESULTS: According to Odom's criteria,
      91.6% achieved favorable outcome. The mean visual analog scale score was improved
      from 8.6 to 3, and the mean neck disability index was improved from 27.9 to 7.3
      (p<0.01). Eighteen cases (75%) showed disc height (DH) decrease. The disc
      invasion was correlated with DH decrease (p<0.05). The disc height decrease
      correlated with static, dynamic changes of shell angle and spur formation
      (p<0.05). Any radiological parameters did not affect the clinical outcome.
      CONCLUSION: AMF is an effective technique for treating unilateral cervical
      radiculopathy. It showed excellent surgical outcomes even in long-term follow
      ups. However, a decrease in DH occurred in a considerable number of patients.
      Disc invasion during surgery may be the trigger of sequential degeneration.

PMID- 25368762
TI  - Central decompressive laminoplasty for treatment of lumbar spinal stenosis :
      technique and early surgical results.
AB  - OBJECTIVE: Lumbar spinal stenosis is a common degenerative spine disease that
      requires surgical intervention. Currently, there is interest in minimally
      invasive surgery and various technical modifications of decompressive lumbar
      laminectomy without fusion. The purpose of this study was to present the author's
      surgical technique and results for decompression of spinal stenosis. METHODS: The
      author performed surgery in 57 patients with lumbar spinal stenosis between 2006
      and 2010. Data were gathered retrospectively via outpatient interviews and
      telephone questionnaires. The operation used in this study was named central
      decompressive laminoplasty (CDL), which allows thorough decompression of the
      lumbar spinal canal and proximal two foraminal nerve roots by undercutting the
      lamina and facet joint. Kyphotic prone positioning on elevated curvature of the
      frame or occasional use of an interlaminar spreader enables sufficient
      interlaminar working space. Pain was measured with a visual analogue scale (VAS).
      Surgical outcome was analyzed with the Oswestry Disability Index (ODI). Data were
      analyzed preoperatively and six months postoperatively. RESULTS: The interlaminar
      window provided by this technique allowed for unhindered access to the central
      canal, lateral recess, and upper/lower foraminal zone, with near-total sparing of
      the facet joint. The VAS scores and ODI were significantly improved at six-month
      follow-up compared to preoperative levels (p<0.001, respectively). Excellent pain
      relief (>75% of initial VAS score) of back/buttock and leg was observed in 75.0%
      and 76.2% of patients, respectively. CONCLUSION: CDL is easily applied, allows
      good field visualization and decompression, maintains stability by sparing
      ligament and bony structures, and shows excellent early surgical results.

PMID- 25368763
TI  - Early Vertebroplasty versus Delayed Vertebroplasty for Acute Osteoporotic
      Compression Fracture : Are the Results of the Two Surgical Strategies the Same?
AB  - OBJECTIVE: In Korea, early vertebroplasty (EVP) or delayed vertebroplasty (DVP,
      which is performed at least 2 weeks after diagnosis) were performed for the
      treatment of acute osteoporotic compression fracture (OCF) of the spine. The
      present study compared the outcomes of two surgical strategies for the treatment
      of single-level acute OCF in the thoracolumbar junction (T12-L2). METHODS: From
      2004 to 2010, 23 patients were allocated to the EVP group (EVPG) and 27 patients
      to the DVP group (DVPG). Overall mean age was 68.3+/-7.9 and minimum follow-up
      period was 1.0 year. Retrospective study of clinical and radiological results was
      conducted. RESULTS: No significant differences in baseline characteristics were
      observed between the two groups. As expected, mean duration from onset to
      vertebroplasty and mean duration of hospital stay were significantly longer in
      the DVPG (17.1+/-2.1 and 17.5+/-4.2) than in the EVPG (3.8+/-3.3 and 10.8+/-5.1,
      p=0.001). Final clinical outcome including visual analogue scale (VAS), Oswestry
      Disability Index, and Odom's criteria did not differ between the two groups.
      However, immediate improvement of the VAS after vertebroplasty was greater in the
      EVPG (5.1+/-1.3) than in the DVPG (4.0+/-1.0, p=0.002). The proportion of cement
      leakage was lower in the EVPG (30.4%) than in the DVPG (59.3%, p=0.039). In
      addition, semiquantitative grade of cement interdigitation was significantly more
      favorable in the EVPG than in the DVPG (p=0.003). Final vertebral body collapse
      and segmental kyphosis did not differ significantly between the two groups.
      CONCLUSION: Our findings suggest that EVP achieves a better immediate surgical
      effect with more favorable cost-effectiveness.

PMID- 25368764
TI  - Sequential Changes of Plasma C-Reactive Protein, Erythrocyte Sedimentation Rate
      and White Blood Cell Count in Spine Surgery : Comparison between Lumbar Open
      Discectomy and Posterior Lumbar Interbody Fusion.
AB  - OBJECTIVE: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are
      often utilized to evaluate for postoperative infection. Abnormal values may be
      detected after surgery even in case of non-infection because of muscle injury,
      transfusion, which disturbed prompt perioperative management. The purpose of this
      study was to evaluate and compare the perioperative CRP, ESR, and white blood
      cell (WBC) counts after spine surgery, which was proved to be non-infection.
      METHODS: Twenty patients of lumbar open discectomy (LOD) and 20 patients of
      posterior lumbar interbody fusion (PLIF) were enrolled in this study.
      Preoperative and postoperative prophylactic antibiotics were administered
      routinely for 7 days. Blood samples were obtained one day before surgery and
      postoperative day (POD) 1, POD3, and POD7. Using repeated measures ANOVA, changes
      in effect measures over time and between groups over time were assessed. All data
      analysis was conducted using SAS v.9.1. RESULTS: Changes in CRP, within treatment
      groups over time and between treatment groups over time were both statistically
      significant F(3,120)=5.05, p=0.003 and F(1,39)=7.46, p=0.01, respectively. Most
      dramatic changes were decreases in the LOD group on POD3 and POD7. Changes in
      ESR, within treatment groups over time and between treatment groups over time
      were also found to be statistically significant, F(3,120)=6.67, p=0.0003 and
      F(1,39)=3.99, p=0.01, respectively. Changes in WBC values also were be
      statistically significant within groups over time, F(3,120)=40.52, p<0.001,
      however, no significant difference was found in between groups WBC levels over
      time, F(1,39)=0.02, p=0.89. CONCLUSION: We found that, dramatic decrease of CRP
      was detected on POD3 and POD7 in LOD group of non-infection and dramatic increase
      of ESR on POD3 and POD7 in PLIF group of non-infection. We also assumed that CRP
      would be more effective and sensitive parameter especially in LOD than PLIF for
      early detection of infectious complications. Awareness of the typical pattern of
      CRP, ESR, and WBC may help to evaluate the early postoperative course.

PMID- 25368765
TI  - Long-term clinical and radiologic outcomes of minimally invasive posterior
      cervical foraminotomy.
AB  - OBJECTIVE: To report long-term clinical and radiological outcomes of minimally
      invasive posterior cervical foraminotomy (MI-PCF) performed in patients with
      unilateral single-level cervical radiculopathy. METHODS: Of forty-six patients
      who underwent MI-PCF for unilateral single-level radiculopathy between 2005 and
      2013, 33 patients were included in the study, with a mean follow-up of 32.7
      months. Patients were regularly followed for clinical and radiological
      assessment. Clinical outcome was measured by visual analogue scale (VAS) for the
      neck/shoulder and arm, and the neck disability index (NDI). Radiological outcome
      was measured by focal/global angulation and disc height index (DHI). Outcomes
      after MI-PCF were evaluated as changes of clinical and radiological parameters
      from the baseline. Mixed effect model with random patients' effect was used to
      test for differences in the clinical and radiological parameters repeat measures.
      RESULTS: There were no complications and all patients had an uneventful recovery
      during the early postoperative period. VAS scores for neck/shoulder and arm
      improved significantly in the early postoperative period (3 months) and were
      maintained with time (p<0.001). NDI improved significantly post-operatively and
      tended to decrease gradually during the follow-up period (p<0.001). There were no
      statistically significant changes in focal and global angulation at follow-up.
      Percent DHIs of the upper adjacent or operated disc were maintained without
      significant changes with time. During the follow-up, same site recurrence was not
      noted and adjacent segment disease requiring additional surgery occurred in two
      patients (6%) on the contra-lateral side. CONCLUSION: MI-PCF provides long-term
      pain relief and functional restoration, accompanied by good long-term
      radiological outcome.

PMID- 25368766
TI  - Predictive factors for a kyphosis recurrence following short-segment pedicle
      screw fixation including fractured vertebral body in unstable thoracolumbar burst
      fractures.
AB  - OBJECTIVE: The technique of short segment pedicle screw fixation (SSPSF) has been
      widely used for stabilization in thoracolumbar burst fractures (TLBFs), but some
      studies reported high rate of kyphosis recurrence or hardware failure. This study
      was to evaluate the results of SSPSF including fractured level and to find the
      risk factors concerned with the kyphosis recurrence in TLBFs. METHODS: This study
      included 42 patients, including 25 males and 17 females, who underwent SSPSF for
      stabilization of TLBFs between January 2003 and December 2010. For radiologic
      assessments, Cobb angle (CA), vertebral wedge angle (VWA), vertebral body
      compression ratio (VBCR), and difference between VWA and Cobb angle (DbVC) were
      measured. The relationships between kyphosis recurrence and radiologic parameters
      or demographic features were investigated. Frankel classification and low back
      outcome score (LBOS) were used for assessment of clinical outcomes. RESULTS: The
      mean follow-up period was 38.6 months. CA, VWA, and VBCR were improved after
      SSPSF, and these parameters were well maintained at the final follow-up with
      minimal degree of correction loss. Kyphosis recurrence showed a significant
      increase in patients with Denis burst type A, load-sharing classification (LSC)
      score >6 or DbVC >6 (p<0.05). There were no patients who worsened to clinical
      outcome, and there was no significant correlation between kyphosis recurrence and
      clinical outcome in this series. CONCLUSION: SSPSF including the fractured
      vertebra is an effective surgical method for restoration and maintenance of
      vertebral column stability in TLBFs. However, kyphosis recurrence was
      significantly associated with Denis burst type A fracture, LSC score >6, or DbVC
      >6.

PMID- 25368767
TI  - Microsurgical treatment and outcome of pediatric supratentorial cerebral
      cavernous malformation.
AB  - OBJECTIVE: The purpose of this study was to investigate the clinical features and
      outcomes of pediatric cavernous malformation (CM) in the central nervous system.
      METHODS: Twenty-nine pediatric patients with supratentorial CM underwent
      microsurgical excision. In selected cases, transparent tubular retractor system
      (TTRS) was used to reduce retraction injury and intraoperative neuromonitoring
      (IONM) was held to preserve functioning cortex. Patients' demographics and
      symptoms were reviewed and surgical outcomes were discussed. RESULTS: THE MAIN
      INITIAL CLINICAL MANIFESTATIONS INCLUDED THE FOLLOWING : seizures (n=13, 45%),
      headache (n=7, 24%), focal neurological deficits (n=3, 10%), and an incidental
      finding (n=6, 21%). Overt hemorrhage was detected in 7 patients (24%). There were
      19 children (66%) with a single CM and 10 (34%) children with multiple CMs. In 7
      cases with deep-seated CM, we used a TTRS to minimize retraction. In 9 cases
      which location of CM was at eloquent area, IONM was taken during surgery. There
      was no major morbidity or mortality after surgery. In the 29 operated children,
      the overall long-term results were satisfactory : 25 (86%) patients had no signs
      or symptoms associated with CMs, 3 had controllable seizures, and 1 had mild
      weakness. CONCLUSION: With the assistance of neuronavigation systems,
      intraoperative neuromonitoring, and TTRS, CMs could be targeted more accurately
      and excised more safely. Based on the satisfactory seizure outcome achieved,
      complete microsurgical excision in children is recommended for CMs presenting
      with seizures but removal of hemosiderin-stained areas seems to be unnecessary.

PMID- 25368768
TI  - Comparison of the Indications and Treatment Results of Burr-Hole Drainage at the
      Maximal Thickness Area versus Twist-Drill Craniostomy at the Pre-Coronal Point
      for the Evacuation of Symptomatic Chronic Subdural Hematomas.
AB  - OBJECTIVE: To analyze the clinical data and surgical results from symptomatic
      chronic subdural hematoma (CSDH) patients who underwent burr-hole drainage (BHD)
      at the maximal thickness area and twist-drill craniostomy (TDC) at the precoronal
      point. METHODS: We analyzed data from 65 symptomatic CSDH patients who underwent
      TDC at the pre-coronal point or BHD at the maximal thickness area. For TDC, we
      defined the pre-coronal point to be 1 cm anterior to the coronal suture at the
      level of the superior temporal line. TDC was performed in patients with CSDH that
      extended beyond the coronal suture, as confirmed by preoperative CT scans.
      Medical records, radiological findings, and clinical performance were reviewed
      and analyzed. RESULTS: Of the 65 CSDH patients, 13/17 (76.4%) with BHD and 42/48
      (87.5%) with TDC showed improved clinical performance and radiological findings
      after surgery. Catheter failure was seen in 1/48 (2.4%) cases of TDC. Five
      patients (29.4%) in the BHD group and four patients (8.33%) in the TDC group
      underwent reoperations due to remaining hematomas, and they improved with a
      second operation, BHD or TDC. CONCLUSION: Both BHD at the maximal thickness area
      and TDC at the pre-coronal point are safe and effective drainage methods for
      symptomatic CSDHs with reasonable indications.

PMID- 25368770
TI  - Cerebral infarction presenting with unilateral isolated foot drop.
AB  - Weakness of the dorsiflexor muscles of the ankle or toe, referred to as foot
      drop, is a relatively common presentation. In most cases, foot drop is caused by
      a lower motor neuron disease such as peroneal peripheral neuropathy, L4-5
      radiculopathic sciatic neuropathy, or polyneuropathy. Although upper motor neuron
      lesions can present as foot drop, the incidence is very rare. Here, we report an
      extremely rare case in which foot drop was the only presenting symptom of
      cerebral infarction. 

PMID- 25368769
TI  - Emerging surgical strategies of intractable frontal lobe epilepsy with cortical
      dysplasia in terms of extent of resection.
AB  - OBJECTIVE: Cortical dysplasia (CD) is one of the common causes of epilepsy
      surgery. However, surgical outcome still remains poor, especially with frontal
      lobe epilepsy (FLE), despite the advancement of neuroimaging techniques and
      expansion of surgical indications. The aim of this study was to focus on surgical
      strategies in terms of extent of resection to improve surgical outcome in the
      cases of FLE with CD. METHODS: A total of 11 patients of FLE were selected among
      67 patients who were proven pathologically as CD, out of a total of 726 epilepsy
      surgery series since 1992. This study categorized surgical groups into three
      according to the extent of resection : 1) focal corticectomy, 2) regional
      corticectomy, and 3) partial functional lobectomy, based on the preoperative
      evaluation, in particular, ictal scalp EEG onset and/or intracranial recordings,
      and the lesions in high-resolution MRI. Surgical outcome was assessed following
      Engel's classification system. RESULTS: Focal corticectomy was performed in 5
      patients and regional corticectomy in another set of 5 patients. Only 1 patient
      underwent partial functional lobectomy. Types I and II CD were detected with the
      same frequency (45.45% each) and postoperative outcome was fully satisfactory
      (91%). CONCLUSION: The strategy of epilepsy surgery is to focus on the different
      characteristics of each individual, considering the extent of real resection,
      which is based on the focal ictal onset consistent with neuroimaging, especially
      in the practical point of view of neurosurgery.

PMID- 25368771
TI  - Cerebral dissecting aneurysms in patients with essential thrombocythemia.
AB  - The etiologies of intracranial artery dissection are various, the exogenous as
      well as inherited connective tissue disorders. We report on a patient who
      presented with diffuse subarachnoid hemorrhage who had been suffered from
      essential thrombocythemia. He was diagnosed to multiple dissecting aneurysms of
      left superior cerebellar artery, left posterior inferior cerebellar artery and
      right pericallosal artery and treated with endovascular coil embolization. 

PMID- 25368772
TI  - Value of perfusion weighted magnetic resonance imaging in the diagnosis of
      supratentorial anaplastic astrocytoma.
AB  - We report perfusion weighted imaging (PWI) findings of nonenhanced anaplastic
      astrocytoma in a 30-year-old woman. Brain magnetic resonance imaging showed a
      nonenhanced brain tumor with mild peritumoral edema on the right medial frontal
      lobe and right genu of corpus callosum, suggesting a low-grade glioma. However,
      PWI showed increased relative cerebral blood volume, relative cerebral blood
      flow, and permeability of nonenhanced brain tumor compared with contralateral
      normal brain parenchyma, suggesting a high-grade glioma. After surgery, final
      histopathological analysis revealed World Health Organization grade III
      anaplastic astrocytoma. This case demonstrates the importance of PWI for
      preoperative evaluation of nonenhanced brain tumors. 

PMID- 25368773
TI  - Intramedullary solitary fibrous tumor of cervicothoracic spinal cord.
AB  - Solitary fibrous tumor is rare benign mesenchymal neoplasm. The spinal solitary
      fibrous tumor is extremely rare. The authors experienced a case of intramedullary
      solitary fibrous tumor of cervicothoracic spinal cord in a 48-year-old man with
      right lower extremity sensory disturbance. Spinal MRI showed intradural mass
      lesion in the level of C7-T1, the margin between the spinal cord and tumor was
      not clear on MRI. A Left unilateral laminectomy and mass removal was performed.
      Intra operative finding, the tumor boundary was unclear from spinal cord and it
      had intramedullary and extramedullary portion. After surgery, patient had good
      recovery and had uneventful prognosis. Follow up spinal MRI showed no recurrence
      of tumor. 

PMID- 25368774
TI  - Acute spontaneous spinal subdural hematoma with vague symptoms.
AB  - Spinal subdural hematoma is a rarely reported disease and spontaneous spinal
      subdural hematomas (SSDH) without underlying pathological changes are even rarer.
      The patients usually show typical symtoms such as back pain, quadriplegia,
      paraplegia or sensory change. But rarely, patients may show atypical symptoms
      such as hemiparesis and misdiagnosed to cerebrovascular accident. We recently
      experienced a case of SSDH, where the patient initially showed vague symptoms,
      such as the sudden onset of headache which we initially misdiagnosed as
      subarachnoid hemorrhage. In this case, the headache of patient improved but the
      neck pain persisted until hospital day 5. Therefre, we conducted the MRI of
      cervical spine and finally confirmed SSDH. The patient was managed conservatively
      and improved without recurrence. In this case report, we discuss the clinical
      features of SSDH with emphasis on the importance of an early diagnosis. 

PMID- 25368775
TI  - Pigmented villonodular synovitis on lumbar spine : a case report and literature
      review.
AB  - Pigmented villonodular synovitis (PVNS) is a benign proliferative joint disease
      with an uncertain etiology that uncommonly involves the spine. We present a case
      of PVNS involving the lumbar spine. A 38-year-old male developed back pain and
      pain in both legs caused by a mass in the L4 region of the right lamina. After
      gross total tumor removal, the symptoms improved. The pathological finding was
      synovial hyperplasia with accumulation of hemosiderin-laden macrophages. He was
      diagnosed with PVNS and experienced no recurrence for up to 2 years after
      surgery. In this report, we review the previous literature and discuss etiology,
      clinical manifestations, diagnosis, and treatment. 

PMID- 25368776
TI  - Trigeminal neuralgia caused by persistent primitive trigeminal artery.
AB  - A 66-year-old man presented with typical trigeminal neuralgia (TN). Magnetic
      resonance angiography (MRA) revealed a primitive trigeminal artery (PTA) that
      came into contact with the trigeminal nerve. Based on MRA, we performed
      microvascular decompression (MVD). In the operational field, we confirmed the PTA
      location and performed MVD successfully. Postoperatively, the patient's pain
      subsided without any complications. 

PMID- 25368777
TI  - Endoscopic Decompression for Optic Neuropathy in McCune-Albright Syndrome.
AB  - McCune-Albright syndrome (MAS) is characterized by a triad of poly/monostotic
      fibrous dysplasia, cafe-au-lait macules and hyperfunctioning endocrinopathies
      including human growth hormone excess. Acromegaly as a manifestation of endocrine
      hyperfunction with MAS is uncommon. Surgical excision may be challenging due to
      the associated severe fibrous dysplasia of the skull base. Through the endoscopic
      procedures, we treated a case of MAS presenting with compressive optic neuropathy
      due to fibrous dysplasia and acromegaly caused by growth hormone secreting
      pituitary adenoma. We reviewed the literature on GH excess in MAS to highlight
      its surgical and medical challenges. 

PMID- 25368778
TI  - Biting of the Tongue in a Patient with a Tracheostomy during Surgery in the
      Supine Position.

PMID- 25368779
TI  - Protective strategies for one-lung ventilation.

PMID- 25368780
TI  - Effect of beach chair position on bispectral index values during arthroscopic
      shoulder surgery.
AB  - BACKGROUND: Bispectral index (BIS) monitoring reduces the cases of intraoperative
      awareness. Several factors can alter BIS readings without affecting the depth of
      anesthesia. We conducted a study to assess the impact of beach chair position
      (sitting position) on BIS readings. METHODS: General anesthesia was administered
      to 30 patients undergoing arthroscopic shoulder surgery. Patients were kept in
      neutral position (supine) for 10 minutes and BIS readings, mean arterial blood
      pressure, heart rate, end-tidal carbon dioxide, and end-tidal sevoflurane were
      recorded. Patients were then shifted to beach chair position. After 15 minutes,
      data were recorded. RESULTS: A significant decrease in BIS values (P < 0.01)
      associated with a position change from neutral position to beach chair position
      was evident. CONCLUSIONS: BIS values are significantly decreased in the beach
      chair position compared with the neutral position and might affect interpretation
      of the depth of anesthesia.

PMID- 25368781
TI  - Dynamic optic nerve sheath diameter responses to short-term hyperventilation
      measured with sonography in patients under general anesthesia.
AB  - BACKGROUND: Rapid evaluation and management of intracranial pressure (ICP) can
      help to early detection of increased ICP and improve postoperative outcomes in
      neurocritically-ill patients. Sonographic measurement of optic nerve sheath
      diameter (ONSD) is a non-invasive method of evaluating increased intracranial
      pressure at the bedside. In the present study, we hypothesized that sonographic
      ONSD, as a surrogate of ICP change, can be dynamically changed in response to
      carbon dioxide change using short-term hyperventilation. METHODS: Fourteen
      patients were enrolled. During general anesthesia, end-tidal carbon dioxide
      concentration (ETCO2) was decreased from 40 mmHg to 30 mmHg within 10 minutes.
      ONSD, which was monitored continuously in the single sonographic plane, was
      repeatedly measured at 1 and 5 minutes with ETCO2 40 mmHg (time-point 1 and 2)
      and measured again at 1 and 5 minutes with ETCO2 30 mmHg (time-point 3 and 4).
      RESULTS: The mean +/- standard deviation of ONSD sequentially measured at four
      time-points were 5.0 +/- 0.5, 5.0 +/- 0.4, 3.8 +/- 0.6, and 4.0 +/- 0.4 mm,
      respectively. ONSD was significantly decreased at time-point 3 and 4, compared
      with 1 and 2 (P < 0.001). CONCLUSIONS: The ONSD was rapidly changed in response
      to ETCO2. This finding may support that ONSD may be beneficial to close ICP
      monitoring in response to CO2 change.

PMID- 25368782
TI  - Laparoscopic appendectomy under spinal anesthesia with dexmedetomidine infusion.
AB  - BACKGROUND: Laparoscopic appendectomy (LA) is rarely performed under regional
      anesthesia because of pneumoperitoneum-related problems. We expected that
      dexmedetomidine would compensate for the problems arising from spinal anesthesia
      alone. Thus, we performed a feasibility study of spinal anesthesia with
      intravenous dexmedetomidine infusion. METHODS: Twenty-six patients undergoing LA
      received spinal anesthesia with intravenous dexmedetomidine infusion. During
      surgery, the patient's pain or discomfort was controlled by supplemental fentanyl
      or ketamine injection, and all adverse effects were evaluated. RESULTS: No
      patient required conversion to general anesthesia, and all operations were
      completed laparoscopically without conversion to open surgery. Seventeen (65.4%)
      patients required supplemental injection of fentanyl or ketamine. Bradycardia
      occurred in seven (26.9%) patients. CONCLUSIONS: Spinal anesthesia with
      dexmedetomidine infusion may be feasible for LA. However, additional analgesia,
      sedation, and careful attention to the potential development of bradycardia are
      needed for a successful anesthetic outcome.

PMID- 25368783
TI  - The effects of intravenous dexmedetomidine on spinal anesthesia: comparision of
      different dose of dexmedetomidine.
AB  - BACKGROUND: In this prospective, randomized, double-blind, placebo-controlled
      trial, we tried to find out appropriate amounts of single-dose dexmedetomidine to
      prolong the duration of spinal anesthesia in a clinical setting. METHODS: Sixty
      patients who were scheduled for unilateral lower limb surgery under spinal
      anesthesia were randomized into three groups receiving normal saline (control
      group, n = 20) or 0.5 or 1.0 ug/kg dexmedetomidine (D-0.5 group, n = 20; D-1, n =
      20) intravenously prior to spinal anesthesia with 12 mg of bupivacaine. The two
      dermatome pinprick sensory regression time, duration of the motor block, Ramsay
      sedation score (RSS), and side effects of dexmedetomidine were assessed. RESULTS:
      The two-dermatome pinprick sensory regression time (57.6 +/- 23.2 vs 86.5 +/-
      24.3 vs 92.5 +/- 30.7, P = 0.0002) and duration of the motor block (98.8 +/- 34.1
      vs 132.9 +/- 43.4 vs 130.4 +/- 50.4, P = 0.0261) were significantly increased in
      the D-0.5 and D-1 groups than in the control group. The RSS were significantly
      higher in the D-0.5 and D-1 groups than in the control group. However, there were
      no patients with oxygen desaturation in dexmedetomidine groups. The incidences of
      hypotension and bradycardia showed no differences among the three groups.
      CONCLUSIONS: Both 0.5 and 1.0 ug/kg of dexmedetomidine administered as isolated
      boluses in the absence of maintenance infusions prolonged the duration of spinal
      anesthesia.

PMID- 25368784
TI  - Volume-controlled versus pressure-controlled ventilation-volume guaranteed mode
      during one-lung ventilation.
AB  - BACKGROUND: The purpose of this study was to investigate the changes in airway
      pressure and arterial oxygenation between ventilation modes during one-lung
      ventilation (OLV) in patients undergoing thoracic surgery. METHODS: We enrolled
      27 patients for thoracic surgery with OLV in the lateral decubitus position. The
      subjects received various modes of ventilation in random sequences during
      surgery, including volume-controlled ventilation (VCV) and pressure-controlled
      ventilation-volume guaranteed (PCV-VG) with a tidal volume (TV) of 8 ml/kg of
      actual body weight. Target-controlled infusion (TCI) with propofol and
      remifentanil was used for anesthesia induction and maintenance. After double
      lumen endobronchial tube (DLT) insertion, the proper positioning of the DLT was
      assessed using a fiberoptic bronchoscope. Peak inspiratory pressure (Ppeak),
      exhaled TV, and arterial blood gas were measured 30 min after each ventilation
      mode. RESULTS: Ppeak was significantly reduced with the PCV-VG mode (19.6 +/- 2.5
      cmH2O) compared with the VCV mode (23.2 +/- 3.1 cmH2O) (P < 0.000). However, no
      difference in arterial oxygen tension was noted between the groups (PCV-VG, 375.8
      +/- 145.1 mmHg; VCV, 328.1 +/- 123.7 mmHg) (P = 0.063). The exhaled TV was also
      significantly increased in PCV-VG compared with VCV (451.4 +/- 85.4 vs. 443.9 +/-
      85.9 ml; P = 0.035). CONCLUSIONS: During OLV in patients with normal lung
      function, although PCV-VG did not provide significantly improved arterial oxygen
      tension compared with VCV, PCV-VG provided significantly attenuated airway
      pressure despite significantly increased exhaled TV compared with VCV.

PMID- 25368785
TI  - Comparison of two fluid warming devices for maintaining body core temperature
      during living donor liver transplantation: Level 1 H-1000 vs. Fluid Management
      System 2000.
AB  - BACKGROUND: Rapid fluid warming has been a cardinal measure to maintain
      normothermia during fluid resuscitation of hypovolemic patients. A previous
      laboratory simulation study with different fluid infusion rates showed that a
      fluid warmer using magnetic induction is superior to a warmer using
      countercurrent heat exchange. We tested whether the simulation-based result is
      translated into the clinical liver transplantation. METHODS: Two hundred twenty
      recipients who underwent living donor liver transplantation between April 2009
      and October 2011 were initially screened. Seventeen recipients given a magnetic
      induction warmer (FMS2000) were matched 1 : 1 with those given a countercurrent
      heat exchange warmer (Level-1 H-1000) based on propensity score. Matched
      variables included age, gender, body mass index, model for end-stage liver
      disease score, graft size and time under anesthesia. Core temperatures were taken
      at predetermined time points. RESULTS: Level-1 and FMS groups had comparable core
      temperature throughout the surgery from skin incision, the beginning/end of the
      anhepatic phase to skin closure. (P = 0.165, repeated measures ANOVA). The degree
      of core temperature changes within the dissection, anhepatic and postreperfusion
      phase were also comparable between the two groups. The minimum intraoperative
      core temperature was also comparable (Level 1, 35.6C vs. FMS, 35.4C, P = 0.122).
      CONCLUSIONS: A countercurrent heat exchange warmer and magnetic induction warmer
      displayed comparable function regarding the maintenance of core temperature and
      prevention of hypothermia during living donor liver transplantation. The
      applicability of the two devices in liver transplantation needs to be evaluated
      in various populations and clinical settings.

PMID- 25368786
TI  - An unexpected increase of entropy in a sleepwalking disorder patient during
      propofol and remifentanil anesthesia: a case report.
AB  - We report a case of increased values of entropy parameters Response Entropy (RE)
      and State Entropy (SE) during intravenous general anesthesia in a sleepwalking
      patient. An ASA class II, 64-year-old woman with stress incontinence underwent
      mid-urethral sling surgery. Prior to surgery, the patient had been administered
      paroxetine, valproic acid and clonazepam for the treatment of sleepwalking
      disorder. After 10 min of target-controlled infusion of propofol and
      remifentanil, entropy values increased up to 94 (RE) and 88 (SE) for 10 min. The
      target effect-site concentrations of anesthetics increased from 4 to 7 ug/ml
      propofol and 4 ng/ml remifentanil, at which point values fell back to adequate
      anesthesia levels. Episodes of recall or of explicit memories did not occur
      during the anesthesia. In conclusion, sleepwalking patients with long-term use
      medications may need increment of anesthetic dose caused by the anesthetic drug
      metabolism activation or impairment or immaturity of inhibitory circuits in
      brain. 

PMID- 25368787
TI  - Anesthetic management of hypertensive crisis in a three-year-old patient with
      undiagnosed severe renal artery stenosis: a case report.
AB  - Pediatric hypertensive crisis is a potentially life threatening medical
      emergency, usually secondary to an underlying disease. Hypertension commonly
      occurs during general anesthesia, and is usually promptly and appropriately
      treated by anesthesiologists. However in children with severe, unexplained, or
      refractory hypertension, it has the potential to cause morbidity and even
      mortality in susceptible patients. We report an anesthetic management of an
      unexpected hypertensive crisis that developed during general anesthesia in a
      three-year-old girl with undiagnosed severe left renal artery stenosis. 

PMID- 25368788
TI  - Anesthetic management of a parturient with placenta previa totalis undergoing
      preventive uterine artery embolization before placental expulsion during cesarean
      delivery: a case report.
AB  - Placenta previa totalis can cause life-threatening massive postpartum hemorrhage,
      and careful anesthetic management is essential. Preventive uterine artery
      embolization (UAE) before placental expulsion was introduced to reduce postpartum
      bleeding in cases of placenta previa totalis. We describe the case of a 40-year
      old woman (gravida 0, para 0) with placenta previa totalis and uterine myomas who
      underwent intraoperative UAE, which was preoperatively planned at the strong
      recommendation of the anesthesiologist, immediately after delivery of a fetus and
      before removal of the placenta during cesarean delivery under spinal-epidural
      anesthesia. After confirming embolization of both uterine arteries, removal of
      the placenta resulted in moderate bleeding. The estimated blood loss was 2.5 L,
      and 5 units of red blood cells were transfused. The parturient was discharged
      uneventfully on postoperative day 4. This case shows that the bleeding risk is
      reduced by intraoperative UAE in a patient with placenta previa totalis, and
      anesthesiologists have an important role in a multidisciplinary team approach. 

PMID- 25368789
TI  - Obstetric anesthesia considerations in Kearns-Sayre syndrome: a case report.
AB  - Kearns-Sayre syndrome (KSS) is a rare mitochondrial myopathy that usually
      develops before 20 years of age. It demonstrates multisystemic involvement with a
      triad of cardinal features: progressive ophthalmoplegia, pigmentary retinopathy,
      and cardiac conduction abnormalities. In addition, patients might have cerebellar
      ataxia, a high content of protein in the cerebrospinal fluid, proximal myopathy,
      multiple endocrinopathies, and renal tubular acidosis. We herein report the
      successful obstetric analgesic and anesthetic management of a 28-year-old
      parturient patient with KSS who required labor analgesia and proceeded to deliver
      by cesarean section. We extrapolate that regional analgesia/anesthesia might be
      beneficial for reducing the metabolic demands associated with the stress and pain
      of labor in patients with KSS. Efficient postoperative analgesia should be
      provided to decrease oxygen requirements. 

PMID- 25368790
TI  - Unexpected and severe postintubation croup after a very short day surgery in a
      pediatric patient: a case report.
AB  - An 18 month-old boy underwent endoscopic foreign body removal under anesthesia on
      an outpatient basis and the operation took approximately 5 minutes. Stridor
      developed in both lung fields 6 hours after emergence from anesthesia, and severe
      croup developed, with cyanosis of the lips and aggravated stridor 20 hours after
      the end of the procedure. The croup resolved with oxygen therapy, intravenous
      dexamethasone, and epinephrine nebulization therapy. In this report, we suggest
      that thorough investigations of the patient's past history, including history of
      any airway problems, and careful monitoring after emergence from anesthesia be
      done in order to decide the proper discharge time of the patient. Further, proper
      prophylaxis following risk stratification is important, especially in patients at
      high risk of postoperative airway obstruction. 

PMID- 25368791
TI  - Empyema Caused by Pseudomonas luteola: A Case Report.
AB  - INTRODUCTION: Pseudomonas luteola is an uncommon opportunistic pathogen. It is
      recognized as an uncommon cause of infections in underlying medical disorders.
      Infections caused by this microorganism are health care associated. CASE
      PRESENTATION: The current study isolated P. luteola from empyema in a patient
      with tuberculous pleurisy, whose susceptibility to trimethoprim-sulfamethoxazole
      differed from previous reports. CONCLUSIONS: P. luteola is resistant to TMP-SMX,
      but in the present case P. luteola was susceptible to TMP-SMX.

PMID- 25368792
TI  - Peganum harmala Aqueous and Ethanol Extracts Effects on Lesions Caused by
      Leishmania major (MRHO/IR/75/ER) in BALB/c Mice.
AB  - BACKGROUND: Leishmaniasis is one of the six most common parasitic infections in
      the tropical regions. There are different therapeutic modalities, however
      therapeutic resistance is developed and resulted in numerous problems. Therefore,
      evaluation of other therapeutic modalities is performed extensively. OBJECTIVES:
      The current study aimed to compare the therapeutic response of cutaneous
      leishmaniasis with Glucantime and Peganum harmala extracts (aqueous and ethanol)
      in the animal model. MATERIALS AND METHODS: The therapeutic response of
      Leishmania major to Glucantime and P. harmala extracts (aqueous and ethanol) in
      animal model was studied in BALB/c mice. These mice were divided into four groups
      according to receiving either one of these three agents, and the control group.
      The therapeutic response was evaluated according to the parasitic load before and
      after treatment and also with measuring the size of the lesions. RESULTS: The
      results showed that ethanol extract of P. harmala had good therapeutic efficacy
      in treatment of lesions in mice (P < 0.05), and the efficacy was significant in
      the eighth week after the treatment. There was also a statistically significant
      difference between the groups regarding the parasitic load (P < 0.05).
      CONCLUSIONS: According to the current study results, it may be concluded that
      ethanol extract of P. harmala is efficient in the treatment of cutaneous
      leishmaniasis, and the efficiency is comparable with that of Glucantime.

PMID- 25368793
TI  - Quinolone Susceptibility and Detection of qnr and aac(6')-Ib-cr Genes in
      Community Isolates of Klebsiella pneumoniae.
AB  - BACKGROUND: Plasmid-mediated quinolone resistance genes (PMQR) have been shown to
      play not only an important role in quinolone resistance, but also resistance to
      other antibiotics, particularly beta-lactams and aminoglycosides. These genes are
      mainly associated with clinical isolates of Enterobacteriaceae. However,
      detection of PMQR genes in the community isolates can increase the dissemination
      rate of resistance determinants among bacteria. OBJECTIVES: This study aimed to
      investigate quinolone resistance and distribution of qnr and aac (6')-Ib-cr genes
      among the community isolates of Klebsiella pneumoniae. MATERIALS AND METHODS:
      Fifty-two K. pneumoniae isolates were collected from the Central Laboratory in
      Karaj between July 2010 and January 2011. Antibacterial susceptibility was
      determined by the disc diffusion method. Quinolone and/or cephalosporin-resistant
      isolates were screened for the presence of qnrA, qnrB, qnrS and aac (6')-Ib-cr
      genes by polymerase chain reaction (PCR). RESULTS: Of the 52 K. pneumoniae
      isolates, 23 were resistant to cephalosporins and/or quinolones. Overall, 7 out
      of the 23 resistant isolates harbored qnr and/or aac (6')-Ib-cr genes (30.4%).
      Among these, 5 isolates were resistant to both classes of antibiotics of which; 3
      carried the aac (6')-Ib-cr gene, one had the qnrS, and one harbored both aac (6')
      Ib-cr and qnrB genes. None of the isolates contained qnrA. Two isolates were
      sensitive to quinolones and resistant to cephalosporins of which; one had qnrS
      and the other carried the aac (6')-Ib-cr gene. CONCLUSIONS: Our study showed that
      30.4% of the quinolone and/or cephalosporin resistant community isolates of K.
      pneumoniae carried PMQR genes. These results confirm that community isolates can
      be an important source for spreading antibiotic resistance determinants among
      Gram negative pathogens. This is the first report from Iran on detection of PMQR
      in the community isolates of K. pneumoniae.

PMID- 25368794
TI  - Prevalence of ochratoxin a in human milk in the khorrambid town, fars province,
      South of iran.
AB  - BACKGROUND: Ochratoxins belong to a group of mycotoxins produced as the secondary
      metabolites by filamentous fungi, such as Aspergillus and Penicillium. These
      toxins may be teratogenic, mutagenic, hepatotoxic, nephrotoxic, and may have
      immunosuppressive effects and pose a serious health problems to exposed humans
      and animals. OBJECTIVES: The present study aimed to determine the level of
      ochratoxin A (OTA) in the samples of mothers' milk in the Khorrambid Town, Fars
      Province, south of Iran. MATERIALS AND METHODS: Between June and July 2011,
      samples of human milk were obtained from 87 mothers. The samples were diluted by
      absolute methanol at 1:4 ratio and after centrifugation, the supernatant was
      directly used to determine the level of OTA using competitive enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Among 87 human milk samples, 84 (96.6%)
      samples had positive results for OTA at a mean level of 24.57 +/- 13.6 ng/L.
      According to the European Union Standard, 14 (16%) positive samples revealed more
      than the maximum limit of 40 ng/L for ochratoxin (range, 1.6-60 ng/L).
      CONCLUSIONS: Presence of OTA in the milk of mothers denotes a probable
      consumption of a contaminated foods. Therefore, regular monitoring of foods for
      presence of mycotoxins for lactating mothers seems necessary.

PMID- 25368795
TI  - Brain tuberculomas: a case report.
AB  - INTRODUCTION: An unusual incidence of tuberculosis in different parts of the body
      is called tuberculomas. The rate of brain tuberculosis is rare. CASE
      PRESENTATION: The following case of tuberculamas of the brain, presented by
      enhancing rings of meninges, is reported because of its rarity. It was a case of
      brain tuberculomas in a 15-year-old girl with primary symptoms of headache and
      general weakness, and no signs of primary pulmonary infection. DISCUSSION: The
      subject underwent computerized tomography (CT) and magnetic resonance imaging
      (MRI) of the brain. Microbiological tests (acid fast bacilli smear-AFB, and
      culture of biopsy specimen) were applied subsequently. According to the results,
      the problem was diagnosed as brain tuberculomas. After operation she was
      completely treated with anti-TB drugs. Although brain tuberculosis is rare, it
      was diagnosed on the basis of histopathology and the patient's successful
      response to anti-tuberculous drug treatment.

PMID- 25368796
TI  - Codon-Optimized Expression and Purification of Truncated ORF2 Protein of
      Hepatitis E Virus in Escherichia coli.
AB  - BACKGROUND: Hepatitis E virus (HEV) is a causative agent of acute hepatitis among
      people of different age groups and has high mortality rate of up to 30% among
      pregnant women. Therefore, primary prevention of HEV infection is essential.
      OBJECTIVES: The aim of this study was to obtain the highly purified truncated
      open reading frames 2 (ORF2) protein, which might be a future HEV vaccine
      candidate. MATERIALS AND METHODS: The truncated orf2 gene (orf2.1), encoding the
      112-660 amino acid of HEV capsid protein sequence, was optimized, synthesized,
      and cloned into pBluescript II SK(+) vector. After subcloning into expression
      vector pET-30a (+), a 193-nucleotide fragment was deleted from the construct and
      the recombinant plasmid pET-30a-ORF2.2 (orf2.2 encodes 112-608 amino acid
      sequence of HEV capsid protein) was constructed and used for transformation of
      Escherichia coli BL21 cells. After induction with isopropyl-beta-D
      thiogalactopyranoside (IPTG) and optimizing the conditions of expression, the
      target protein was highly expressed and purified by Ni(2+)-chelate affinity
      chromatography. The expressed and purified protein was analyzed by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting.
      RESULTS: The subcloning was confirmed by PCR, restriction enzyme digestion, and
      DNA sequencing of recombinant plasmid pET30a-ORF2.2. The results obtained from
      optimizing the expression conditions showed that the highest expression of the
      protein was obtained by adding IPTG at a final concentration of 1 mM at 37C for
      four hours. The expression and purification of truncated ORF2 protein was
      confirmed by SDS-PAGE and western blotting. SDS-PAGE analysis showed a protein
      band of about 55 kDa. SDS-PAGE of the purified protein revealed that the highest
      amount of target protein in elution buffer at the pH of 4.5 was obtained. The
      yield of the purified protein was about 1 mg/L of culture media. CONCLUSIONS: In
      this study, the optimized truncated ORF2 protein was expressed in E. coli
      successfully and the highly purified protein was obtained, which can be a
      potential vaccine candidate and as an antigen in ELISA to diagnose HEV
      infections.

PMID- 25368797
TI  - Antibacterial Activity of Various Plants Extracts Against Antibiotic-resistant
      Aeromonas hydrophila.
AB  - BACKGROUND: Aeromonas hydrophila cause one of the most important diseases in
      fishes and lead to economic losses, and may be contaminated human beings.
      OBJECTIVES: The current research aimed to investigate the anti-bacterial activity
      shown by the extracts prepared from different parts of Olea europea, Myrtus
      communis, Thymus vulgaris, Rosmarinuis officinalis, and Achillea falcata that
      grow in Syria against A. hydrophila that causes the most dangerous bacterial
      diseases in fish. MATERIALS AND METHODS: THE STUDY WAS PERFORMED IN FOUR STAGES:
      First of all, the presence of A. hydrophila was investigated in 450 Samples of
      Cyprinus Carpio fish using blood agar, Trypticase soya agar, and Analytical
      Profile Index (API20E). Secondly, the plants extract was obtained using water,
      absolute alcohol, then ether using Soxhlet extraction apparatus and rotary vacuum
      evaporator. Thirdly, the antibacterial activity of some antibiotics on these
      bacteria was evaluated by disk diffusion method. Finally, the antibacterial
      effect of the extracts was determined by disk diffusion method. RESULTS: The
      studied antibiotics showed no antibacterial activity against these bacteria,
      except amikacin which had an acceptable effectiveness. However, the ethanol
      extracts of the studied plants revealed different antibacterial effects against
      A. hydrophila which showed antibiotic resistant. T. vulgaris extract had the
      strongest effect, whereas O. europea extract had the weakest activity. The water
      and ether petroleum extracts had no antibacterial activities. CONCLUSIONS:
      Ethanol extracts of the studied plants had different antibacterial effects
      against antibiotic-resistant A. hydrophila. T. vulgaris had the highest activity,
      R. officinalis had the second, and M. communis and A. falcate were in the third
      place, while the O. europea had the weakest antibacterial activity.

PMID- 25368798
TI  - Antibacterial Efficacy of Aqueous Ozone in Root Canals Infected by Enterococcus
      faecalis.
AB  - BACKGROUND: In endodontics, the elimination of resistant bacteria such as
      Enterococcus faecalis plays an important role for treatment success in root
      canals. Therefore, new alternative irrigants (instead of sodium hypochlorite)
      have been researched to achieve ideal endodontic treatment. OBJECTIVES: The aim
      of the present study was to evaluate and to compare the antibacterial effect of
      aqueous ozone with different concentrations and techniques of application (manual
      and ultrasonic) against E. faecalis in human root canals. PATIENTS AND METHODS:
      Eighty single-root mandibular premolar teeth were selected, prepared and
      sterilized. E. faecalis was incubated in the root canals and kept at 37 degrees C
      for 24 h. The teeth were divided into four main groups each has 20 members: NaOCl
      (positive control) group; 8 ppm aqueous ozone group; 12 ppm aqueous ozone group;
      and 16 ppm aqueous ozone group. While half of the specimens were disinfected with
      aqueous ozone by manual technique, the other half was disinfected with the
      aqueous ozone by ultrasonic technique. Conventional irrigation technique was
      simultaneously applied with ultrasonic vibration that was produced by VDW.ULTRA
      device. The disinfection procedures were performed for 180 s to ensure
      standardization of all the working groups. Paper points (placed in the root
      canals before and after the disinfection procedures) were transferred to
      Eppendorf tubes containing 0.5 mL of brain heart infusion broth. Then, 50 MUL of
      the suspension was inoculated onto broth agar media. Microbial colonies were
      counted, and the data were evaluated statistically using 2-way analysis of
      variance (ANOVA) and Tukey tests. RESULTS: Although the antibacterial effect of
      16 ppm aqueous ozone using a manual technique had an insufficient effect, its
      ultrasonic application technique resulted in complete disinfection in the root
      canals. CONCLUSIONS: The bactericidal activity of high concentration of aqueous
      ozone combined with ultrasonic application technique showed efficacy similar to
      that of 5.25% NaOCl in root canals.

PMID- 25368799
TI  - Seroprevalence study of leptospirosis among rice farmers in khuzestan province,
      South west iran, 2012.
AB  - BACKGROUND: Leptospirosis as an emerging infectious disease is considered as an
      important public health problem worldwide. OBJECTIVES: The current study aimed to
      identify potential risks for leptospirosis among rice farmers in Khuzestan
      province, Iran. PATIENTS AND METHODS: A cross-sectional study was carried out in
      Khuzestan, South west Iran, from October to December, 2012. Randomly selected
      participants were placed in two groups: Rice farmers as cases, and non-farmers as
      controls. Blood samples obtained from the participants were tested for IgM anti
      leptospira antibodies using Serion ELISA classic ESR 125M. The assays were
      performed and interpreted according to the manufacturer's instructions. A
      questionnaire including variables related to Leptospira spp. exposure was
      administered to each participant. SPSS software version 16 was employed; Chi
      square and Fisher's exact tests were used to analyze data. RESULTS: Of the total
      288 samples, 65 (22.5%) were positive for IgM anti-leptospira antibodies. Among
      the positive samples, 52 (36.1%) were from the case (rice farmer) and 14 (9.7%)
      from the control groups. There was a significant difference between the case and
      control groups regarding leptospiral infection (P < 0.0001). Mean age in male and
      female in the case and control groups were 44.2, 41.9 and 43.5, 41.2 years,
      respectively (P > 0.05). In the case group, males and those more than 35 years
      were at a higher risk of infection. CONCLUSIONS: Rice farmers are significantly
      infected with leptospirosis, and infection prevalence is highly affected by
      gender (male) and age (above 35 years). Rice farming parts of Khuzestan, Iran may
      be considered as endemic for leptospirosis.

PMID- 25368800
TI  - Molecular and Serological Evaluation of Toxoplasma gondii Infection in Reared
      Turkeys in Fars Province, Iran.
AB  - BACKGROUND: Toxoplasmosis is a parasitic disease caused by the protozoan
      Toxoplasma gondii. This parasite infects most of warm-blooded animals, including
      birds. Turkeys are one of these animals which might be infected by this parasite.
      Little is known about the prevalence of T. gondii in turkeys in Iran. OBJECTIVES:
      The current study aimed to evaluate the rate of Toxoplasma infection in turkeys
      in Fars Province, Southern Iran. MATERIALS AND METHODS: Sera and tissues (brain,
      neck and tongue) of 54 turkeys were collected from Shiraz slaughterhouse in Fars
      province. Anti-Toxoplasma antibodies were assessed in the collected sera using
      modified agglutination test (MAT), while tissues were evaluated by polymerase
      chain reaction (PCR) and bioassay methods. RESULTS: T. gondii antibodies (MAT
      titer: >= 1:40) were found in 89.8% of turkeys. T. gondii DNA was detected in
      61.6% of turkey tissues and brain had the highest rate of infection. Brain
      tissues from each animal were bioassayed and Toxoplasma tissue cysts were found
      in 11.5% and Toxoplasma DNA in 62% of inoculated mice. CONCLUSIONS: Results of
      this study validated a relatively high level of Toxoplasma infection in reared
      turkeys and turkey meat might be considered as an infection sources for human.

PMID- 25368801
TI  - The Effect of Aqueous Extract of Glycyrrhiza glabra on Herpes Simplex Virus 1.
AB  - BACKGROUND: Herpes Simplex Virus 1 (HSV-1) resistance to drugs and the side
      effects of drugs have drawn the attention of investigators to herbal plants.
      OBJECTIVES: The main aim of the current research was to investigate the effects
      of Glycyrrhiza glabra (liquorice root) on HSV-1. One of the objectives of the
      current research was to determine the efficacy and the effect of the elapsed
      incubation time of treating the Vero cells infected with HSV-1 by G. glabra. In
      addition, the effect of cells pretreatment with licorice root extract,
      preincubation of virus with licorice root extract, and the antiviral activity
      were assessed. PATIENTS AND METHODS: Vero cells were incubated after adding
      different concentrations of aqueous extracts of G. glabra. The cells were
      incubated during various time courses. Cytotoxicity assay, determining the 50%
      tissue culture infectious dose (TCID50), and incubation of HSV-1 with licorice
      root extract prior to viral infection were performed. RESULTS: Internal
      association among different experiment groups showed the significant difference
      in the efficacy of the extract with regard to incubation period between one and
      four hours, one and eight hours, four and 12 hours, and eight and 12 hours.
      Moreover, there was a significant difference with regard to efficacy among the
      pretreatment of cells with extract for two hours, incubation of virus with
      extract for one hour, incubation of virus with extract for two hours.
      CONCLUSIONS: G. glabra showed the characteristics of a novel antiviral
      medication; however, more in vitro experiments are needed to determine the
      antiherpetic activities of the G. glabra.

PMID- 25368802
TI  - Searching the Staphylococcal Superantigens: Enterotoxins A, B, C, and TSST1 in
      Synovial Fluid of Cases With Negative Culture Inflammatory Arthritis.
AB  - BACKGROUND: Accurate and rapid diagnosis of bacterial arthritis is not always
      possible in unvaccinated (Streptococcus pneumoniae and Haemophilus influenzae
      type B) children in Iran. OBJECTIVES: Searching the staphylococcal superantigen
      (entrotoxin A, B, C and TSST1) in synovial fluid of cases with inflammatory
      arthritis. PATIENTS AND METHODS: This cross sectional study was implemented in
      the pediatric and orthopedic wards, Rasoul Akram Hospital, Tehran, Iran (2008
      2010) upon synovial fluid (SF) aspirated from 66 children (five months to 16
      years; mean age 11 +/- 3.8 years) with monoarthritis. Staphylococcal
      supperantigens (enterotoxins A, B, C, TSST1) were assessed by Enzyme-linked
      immunosorbent assay (ELISA) in synovial fluid of cases with inflammatory
      arthitis. Staphylococcal superantigens compared between cases with positive and
      negative Staphylococcus aureus culture (P < 0.05 was significant). RESULTS: S.
      aureus was the most common cause of septic arthritis. Positive S. aureus culture
      in SF was reported in 10.6% (7/66) of the cases. Enterotoxin A was the least
      common type of superantigens found even in SF negative culture; 47% of the cases
      had one or more staphylococcal superantigens. Enterotoxin A was the least common
      type in SF; there was poor agreement between positive culture for S. aureus and
      presence of enterotoxins B, C, and TSST1 in SF, and intermediate agreement (KAPPA
      Index = 0.67) for enterotoxin A. CONCLUSIONS: A possible role (%47) for
      staphylococcal toxins was defined even in SF negative cultures obtained from
      monoarthritis cases. Failure in isolation of organisms might be due to natural un
      growth of microorganism in synovial fluid, and previous antibiotic usage or low
      technical methods. It could not be determined from the data obtained in the
      current investigation whether or not staphylococcal toxins (superantigens) play a
      pathogenic role without direct invasion of the organism. It is recommend to use
      complementary methods for searching the S. aureus superantigens in future
      studies.

PMID- 25368803
TI  - Diabetic foot: infections and outcomes in Iranian admitted patients.
AB  - BACKGROUND: Diabetes mellitus (along with its complications) has become a global
      problem. Diabetic foot infection, among the most common complications, is
      responsible for 40 to 50% of foot amputations. Antibiotic-resistant
      microorganisms, however, have compromised empiric therapy in the infected
      patients. OBJECTIVES: The current study aimed to determine the most common
      microorganisms involved in diabetic foot infection in order to minimize the
      failure of antibiotic therapy and the risk of developing complications. PATIENTS
      AND METHODS: All patients with diabetic foot infection admitted to the infectious
      diseases, surgery and endocrinology wards of two teaching hospitals from 2007 to
      2010 (n = 196) were recruited. In this retrospective study, demographic
      characteristics, type of lesions, history of hospitalization/antibiotic therapy,
      isolated microorganisms, clinical complications, administered treatment (medical
      or surgical) and outcome were recorded. RESULTS: Patients' mean age was 60.84 (+/
      10.30) years. Totally, 113 (57.65%) of the patients were male and 83 (42.35%)
      were female. According to Wagner's grading, deep ulcers with/without
      osteomyelitis accounted for the majority of lesions. A single microorganism was
      isolated (most common: Escherichia coli, Staphylococcus aureus and Klebsiella
      spp.) from 81 of the patients (80.20%); while for the remaining polymicrobial
      infection was reported. Isolated pathogens showed no significant correlation with
      duration of diabetes, type of the lesions (P = 0.13) and history of
      hospitalization (P = 0.61). The majority of patients (n = 118, 60.20%) were
      treated surgically; however 11 patients expired due to sepsis. Amputation (most
      common at toes and below the knee) was performed for 89 patients (45.40%). The
      response rate to medical treatment was 31.6% for single-pathogen and 10% for
      polymicrobial infection (with a 30% mortality rate). CONCLUSIONS: Physicians are
      recommended to take microbiological cultures before starting empirical therapy
      recommended to cover Gram-negative microorganisms in order to lower the risk of
      antibiotic resistance.

PMID- 25368804
TI  - Construction of a Synthetically Engineered nirB Promoter for Expression of
      Recombinant Protein in Escherichia coli.
AB  - BACKGROUND: Anaerobic-inducible promoters are alternatives of chemical-inducible
      promoters for expression of recombinant proteins especially in conditions where
      chemical induction is not possible or anaerobic conditions are preferable. The
      nirB promoter is the promoter of the first gene of nir operon in Escherichia
      coli, which encodes NADH-dependent nitrite reductase. This promoter is naturally
      induced under anaerobic conditions and upregulated by nitrite and nitrate.
      OBJECTIVES: The current study was carried out to construct a synthetic nirB
      promoter that does not respond to chemical inducers (nitrite or nitrate), but
      instead responds to anaerobic induction. For this purpose, a new plasmid was
      constructed (pFSnirB78-23LTB), which contains a synthetic nirB promoter. The
      activity of this plasmid was evaluated in E. coli under both aerobic and
      anaerobic conditions and in response to chemical inducers, nitrite and nitrate.
      MATERIALS AND METHODS: A synthetic nirB promoter was firstly cloned into a pKK223
      derivative plasmid and then the heat labile toxin B subunit gene (LTB) of
      entrotoxigenic E. coli was cloned under the control of this promoter. The
      inducibility of this plasmid in E. coli was measured under anaerobic conditions
      in the presence or absence of nitrite or nitrate by ganglioside GM1 ELISA.
      RESULTS: Our data showed that this promoter is strongly induced under anaerobic
      conditions while it showed much lower activity (11%) under aerobic conditions. In
      contrast to the native promoter, this promoter was not induced by chemical
      inducers, nitrite or nitrate. CONCLUSIONS: This study showed that the recombinant
      protein produced under the control of synthetic nirB promoter has critical
      characteristics such as pentamer formation, receptor recognition ability and
      conservation of antigenic epitopes. In addition, the data showed anaerobiosis and
      chemical inducers had no adverse effects on recombinant proteins. Based on the
      results, this synthetic promoter is suitable for use in live delivery vaccines or
      drug systems and for production of recombinant proteins especially oxygen
      sensitive proteins.

PMID- 25368805
TI  - Microbial Susceptibility and Plasmid Profiles of Methicillin-Resistant
      Staphylococcus aureus and Methicillin-Susceptible S. aureus.
AB  - BACKGROUND: Today, significant increase in the prevalence and emergence of
      methicillin-resistant Staphylococcus aureus (MRSA) is a serious public health
      concern and is likely to have a dramatic negative impact on many current medical
      practices. Therefore, identification of MRSA strains is important for both
      clinical and epidemiological implications. OBJECTIVES: The present study was
      carried out to determine the frequency of methicillin resistant; antibiotic
      susceptibility and plasmid profiles of S. aureus recovered from different types
      of clinical samples of patients in Zabol, Iran. MATERIAL AND METHODS: Clinical
      samples from 500 outpatient and hospitalized patients were tested for S. aureus.
      The susceptibility of 106 S. aureus to 11 antibiotics was evaluated by the disk
      diffusion method and Etest oxacillin strips. The presence of mecA gene was
      investigated by polymerase chain reaction (PCR). The plasmid profile patterns of
      all isolates were determined by a modified alkaline lysis method. RESULTS: A
      total of 67 (63.20%) strains were found to be MRSA isolates. Most of MRSA
      isolates showed high level of resistance to ampicillin, erythromycin, nalidixic
      acid, penicillin, and tetracycline. Twenty-six percent of MRSA isolates showed
      high level of resistance to oxacillin (minimum inhibitory concentration [MIC] >=
      256 MUg/mL). mecA gene was detected among 62 MRSA isolates. Totally, 75 isolates
      of both strains harbored plasmid. CONCLUSIONS: Resistance to oxacillin and other
      antibiotics was high, and most of the isolates were found to be multi-drug
      resistance (MDR). Plasmid analysis of representative S. aureus isolates also
      demonstrates the presence of a wide range of plasmid sizes, with no consistent
      relationship between plasmid profiles and resistance phenotypes. Regular
      surveillance of hospital infections and monitoring of their antibiotic
      sensitivity patterns are required to reduce MRSA prevalence. High prevalence and
      multi-drug resistance of MRSA isolates in southeast of Iran could be considered
      as an urgent warning for public health.

PMID- 25368806
TI  - Biofilm Formation and Susceptibility to Amphotericin B and Fluconazole in Candida
      albicans.
AB  - BACKGROUND: The ability of Candida albicans to form biofilms and adhere to host
      tissues and biomaterial surfaces is an important factor in its pathogenesis. One
      of the main characteristics of biofilms is their resistance to broad-spectrum
      anti-microbial drugs. OBJECTIVES: In the present study the formation of biofilm
      by C. albicans from different sources was evaluated. In addition, the minimum
      biofilm inhibitory concentration (MBIC) for two antifungals was evaluated.
      MATERIALS AND METHODS: In total, 120 isolates of C. albicans from different
      sources (patients with vaginitis, patients with candiduria, bucal cavity and
      environmental surfaces) were collected. Biofilm formation was determined by the
      96-well micro-titeration plate method. MBIC testing was also performed, using the
      calorimetric indicator resazurin for amphotericin B and fluconazole. RESULTS: The
      results indicated that 100% of C. albicans isolates from different sources had
      the ability to form biofilms in vitro. Amongst these isolates, 83.3% of isolates
      had the maximum potential (4+) to form biofilms, while only one (0.9%) of
      isolates had the minimum ability (1+) to form biofilms. Our results showed that
      65.0% of the tested isolates are sensitive to amphotericin B at amounts lower
      than 10 ug/mL, while only 26.7% are sensitive to fluconazole (had MBIC < 10
      ug/mL). CONCLUSIONS: Although biofilm formation was detected in all tested
      isolates, there were differences in the ability to form biofilms between isolates
      from different sources. In addition, there were differences in the MBIC against
      the two examined antifungals, amphotericin B and fluconazole.

PMID- 25368807
TI  - Changes in various metabolic parameters in blood and milk during experimental
      Escherichia coli mastitis for primiparous Holstein dairy cows during early
      lactation.
AB  - BACKGROUND: The objective of this study was to characterize the changes in
      various metabolic parameters in blood and milk during IMI challenge with
      Escherichia coli ( E. coli ) for dairy cows during early lactation. Thirty,
      healthy primiparous Holstein cows were infused (h = 0) with ~20-40 cfu of live E.
      coli into one front mammary quarter at ~4-6 wk in lactation. Daily feed intake
      and milk yield were recorded. At -12, 0, 3, 6, 12, 18, 24, 36, 48, 60, 72, 96,
      108, 120, 132, 144, 156, 168, 180 and 192 h relative to challenge rectal
      temperatures were recorded and quarter foremilk was collected for analysis of
      shedding of E. coli. Composite milk samples were collected at -180, -132, -84, 
      36, -12, 12, 24, 36, 48, 60, 72, 84, 96, 132 and 180 h relative to challenge (h =
      0) and analyzed for lactate dehydrogenase (LDH), somatic cell count, fat,
      protein, lactose, citrate, beta-hydroxybutyrate (BHBA), free glucose (fglu), and
      glucose-6-phosphate (G6P). Blood was collected at -12, 0, 3, 6, 12, 18, 24, 36,
      60, 72, 84, 132 and 180 h relative to challenge and analyzed for plasma non
      esterified fatty acids (NEFA), BHBA and glucose concentration. A generalized
      linear mixed model was used to determine the effect of IMI challenge on metabolic
      responses of cows during early lactation. RESULTS: By 12 h, E. coli was recovered
      from challenged quarters and shedding continued through 72 h. Rectal temperature
      peaked by 12 h post-challenge and returned to pre-challenge values by 36 h post
      IMI challenge. Daily feed intake and milk yield decreased (P <0.05) by 1 and 2 d,
      respectively, after mastitis challenge. Plasma BHBA decreased (12 h; P <0.05)
      from 0.96 +/- 1.1 at 0 h to 0.57 +/- 0.64 mmol/L by 18 h whereas concentration of
      plasma NEFA (18 h) and glucose (24 h) were significantly greater, 11 and 27%,
      respectively, after challenge. In milk, fglu, lactose, citrate, fat and protein
      yield were lower whereas yield of BHBA and G6P were higher after challenge when
      compared to pre-challenge values. CONCLUSIONS: Changes in metabolites in blood
      and milk were most likely associated with drops in feed intake and milk yield.
      However, the early rise in plasma NEFA may also signify enhanced adipose tissue
      lipolysis. Lower concentrations of plasma BHBA may be attributed to an increase
      transfer into milk after IMI. Decreases in both milk lactose yield and % after
      challenge may be partly attributed to reduced conversion of fglu to lactose.
      Rises in G6P yield and concentration in milk after challenge (24 h) may signify
      increased conversion of fglu to G6P. Results identify changes in various
      metabolic parameters in blood and milk after IMI challenge with E. coli in dairy
      cows that may partly explain the partitioning of nutrients and changes in milk
      components after IMI for cows during early lactation.

PMID- 25368808
TI  - A call for attention to developmental disabilities in dental care.

PMID- 25368809
TI  - Comparison of autogenous tooth bone graft and synthetic bone graft materials used
      for bone resorption around implants after crestal approach sinus lifting: a
      retrospective study.
AB  - PURPOSE: This retrospective study compares the amount of bone resorption around
      implants between an autogenous tooth bone graft (AutoBT) and a synthetic bone
      graft after a bone-added crestally approached sinus lift with simultaneous
      implant placements. METHODS: In all, 37 patients participated in this study.
      Seventeen patients were grouped as group I and underwent an AutoBT-added sinus
      lift using the crestal approach. The remaining 20 patients were grouped as group
      II and underwent synthetic bone grafting. Both groups received the implant
      placements simultaneously. Of the 37 participating patients, only 22 patients
      were included in the final results: Eleven patients of group I and 11 patients of
      group II. Before the surgery, the distance from the alveolar crest to the sinus
      floor was measured using panoramic radiography. After the surgery, the distance
      was measured again from the neck of the implant thread to the most superior
      border of the added graft materials. Then, the amount of sinus lift was
      calculated by comparing the two panoramic radiographs. After a year, a panoramic
      radiograph was taken to calculate the resorption of the bone graft material from
      the radiograph that was taken after the surgery. The significance of the
      resorption amount between the two types of graft materials was statistically
      analyzed. RESULTS: The bone height was increased to an average of 4.89 mm in
      group I and 6.22 mm in group II. The analysis of panoramic radiographs 1 year
      after the surgery showed an average bone resorption of 0.76 mm and 0.53 mm,
      respectively. However, the degree of lifting (P=0.460) and the amount of bone
      grafted material resorption (P=0.570) showed no statistically significant
      difference. CONCLUSIONS: Based on this limited study, AutoBT can be considered a
      good alternative bone graft to a synthetic bone graft in a bone-added sinus lift,
      when extraction is necessary prior to the surgery.

PMID- 25368810
TI  - Evaluation of alveolar crest bone loss via premolar bitewing radiographs:
      presentation of a new method.
AB  - PURPOSE: This study aimed to assess the interdental bone level in premolar
      bitewing radiographs while retracting the cheeks. METHODS: Seventy-two horizontal
      bone defects were created on dried mandibles and maxillae. The distance from the
      bone level to the cement-enamel junction of premolars was detected by a modified
      digital caliper (considered the gold standard). The reliability of all
      radiographs was assessed by intraclass correlation coefficient (ICC), and the
      validity was compared to the gold standard using the analysis of variance test. P
      values less than 0.05 were considered statistically significant. RESULTS: This
      study showed that the reliability of radiographs without a cheek simulator and
      with 0.16 second exposure time was significantly higher than that of the two
      other groups (ICC=0.96 compared to 0.93 and 0.88, respectively). The results from
      the radiographs without a cheek simulator and with 0.16 second exposure time were
      more similar to the gold standard measures than those of the two other groups,
      although the difference was not statistically significant. CONCLUSIONS:
      Retracting the buccal soft tissue plays an important role in increasing the
      accuracy of radiographs in detecting the interdental alveolar bone level and
      produces more accurate results than increasing the exposure time, although it
      does not have a significant role in reliability of results.

PMID- 25368811
TI  - A comparative evaluation of CO2 and erbium-doped yttrium aluminium garnet laser
      therapy in the management of dentin hypersensitivity and assessment of mineral
      content.
AB  - PURPOSE: Dentin hypersensitivity is a potential threat to oral health. Laser
      irradiation may provide reliable and reproducible treatment but remains
      controversial. The present study aimed to evaluate the effects of CO2 or erbium
      doped yttrium aluminium garnet (Er:YAG) laser therapy, and to assess mineral
      content. METHODS: Eighteen human single-rooted teeth affected with advanced
      periodontitis were obtained. Buccal and lingual surfaces were planed to form 36
      specimens. Ethylenediaminetetraacetic acid gel (24%) was applied to remove the
      smear layer and simulate hypersensitive teeth. The experimental groups were:
      group 1, control (no irradiation); group 2, CO2 laser (repetitive pulsed mode, 2
      W, 2.7 J/cm(2)); and group 3, Er:YAG laser (slight contact mode, 40 mJ/pulse and
      10 Hz). To evaluate dentinal tubule occlusion, six specimens per group (2-mm
      thickness) were prepared and observed using scanning electron microscopy (SEM)
      for calculation of the occlusion percentage. To evaluate the mineral content, six
      specimens per group (0.6-mm thickness) were used, and then the levels of Ca, K,
      Mg, Na, and P were measured by inductively coupled plasma-atomic emission
      spectrometry. In addition, the surface temperature of the specimens during laser
      irradiation was analyzed by a thermograph. RESULTS: The SEM photomicrographs
      indicated melted areas around exposed dentinal tubules and a significantly
      greater percentage of tubular occlusion in the CO2 and Er:YAG laser groups than
      the control, and in the Er:YAG group than the CO2 laser group. In addition, no
      significant differences were noted among the experimental groups for the mineral
      elements analyzed. The CO2 laser group showed an evident thermal effect compared
      to the Er:YAG group. CONCLUSIONS: CO2 and Er:YAG laser are effective in treating
      dentin hypersensitivity and reducing its symptoms. However, the Er:YAG laser has
      a more significant effect; thus, it may constitute a useful conditioning item.
      Furthermore, neither CO2 nor Er:YAG lasers affected the compositional structure
      of the mineral content.

PMID- 25368812
TI  - Human CD103(+) dendritic cells promote the differentiation of Porphyromonas
      gingivalis heat shock protein peptide-specific regulatory T cells.
AB  - PURPOSE: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3,
      are known to play a pivotal role in immunoregulatory function in autoimmune
      diseases, cancers, and graft rejection. Dendritic cells (DCs) are considered the
      major antigen-presenting cells (APCs) for initiating these T-cell immune
      responses, of which CD103(+) DCs are derived from precursor human peripheral
      blood mononuclear cells (PBMCs). The aim of the present study was to evaluate the
      capacity of these PBMC-derived CD103(+) DCs to promote the differentiation of
      antigen-specific Tregs. METHODS: Monocyte-derived DCs were induced from CD14(+)
      monocytes from the PBMCs of 10 healthy subjects. Once the CD103(+) DCs were
      purified, the cell population was enriched by adding retinoic acid (RA). Peptide
      numbers 14 and 19 of Porphyromonas gingivalis heat shock protein 60 (HSP60) were
      synthesized to pulse CD103(+) DCs as a tool for presenting the peptide antigens
      to stimulate CD3(+) T cells that were isolated from human PBMC. Exogenous
      interleukin 2 was added as a coculture supplement. The antigen-specific T-cell
      lines established were phenotypically identified for their expression of CD4,
      CD25, or Foxp3. RESULTS: When PBMCs were used as APCs, they demonstrated only a
      marginal capacity to stimulate peptide-specific Tregs, whereas CD103(+) DCs
      showed a potent antigen presenting capability to promote the peptide-specific
      Tregs, especially for peptide 14. RA enhanced the conversion of CD103(+) DCs,
      which paralleled the antigen-specific Treg-stimulating effect, though the
      differences failed to reach statistical significance. CONCLUSIONS: We
      demonstrated that CD103(+) DCs can promote antigen-specific Tregs from naive T
      cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA was
      an effective reagent that induces mature DCs with the typical phenotypic
      expression of CD103 that demonstrated the functional capability to promote
      antigen-specific Tregs.

PMID- 25368814
TI  - Tomographic and histometric analysis of autogenous bone block and synthetic
      hydroxyapatite block grafts without rigid fixation on rabbit calvaria.
AB  - PURPOSE: The preferred material for bone augmentation beyond the envelope of
      skeletal bone is the bone block graft, due to its dimensional stability. We
      evaluated the necessity of rigid fixation for the bone block graft, and compared
      the bone regeneration and volume maintenance associated with grafting using a
      synthetic hydroxyapatite block (HAB) and an autogenous bone block (ABB) without
      rigid fixation on rabbit calvaria over two different periods. METHODS: Cylinder
      shaped synthetic HAB and ABB were positioned without fixation on the rabbit
      calvarium (n=16). The animals were sacrificed at 4 or 8 weeks postoperatively,
      and the grafted materials were analyzed at each healing period using
      microcomputed tomography and histologic evaluation. RESULTS: Integration of the
      graft and the recipient bed was observed in all specimens, although minor
      dislocation of the graft materials from the original position was evident in some
      specimens (six ABB and ten HAB samples). A tendency toward progressive bone
      resorption was observed in the grafted ABB but not in the grafted HAB, which
      maintained an intact appearance. In the HAB group, the area of new bone increased
      between 4 and 8 weeks postoperatively, but the difference was not statistically
      significant. CONCLUSIONS: The nonfixed HAB was successfully integrated into the
      recipient bed after both healing periods in the rabbit calvaria. In spite of
      limited bone formation activity in comparison to ABB, HAB may be a favorable
      substitute osteoconductive bone material.

PMID- 25368813
TI  - Early bone healing onto implant surface treated by fibronectin/oxysterol for cell
      adhesion/osteogenic differentiation: in vivo experimental study in dogs.
AB  - PURPOSE: This study aimed to evaluate the effects of fibronectin and oxysterol
      immobilized on machined-surface dental implants for the enhancement of cell
      attachment and osteogenic differentiation, on peri-implant bone healing in the
      early healing phase using an experimental model in dogs. METHODS: Five types of
      dental implants were installed at a healed alveolar ridge in five dogs: a
      machined-surface implant (MI), apatite-coated MI (AMI), fibronectin-loaded AMI
      (FAMI), oxysterol-loaded AMI (OAMI), and sand-blasted, large-grit, acid-etched
      surface implant (SLAI). A randomly selected unilateral ridge was observed for 2
      weeks, and the contralateral ridge for a 4-week period. Histologic and
      histometric analyses were performed for the bone-to-implant contact proportion
      (BIC) and bone density around the dental implant surface. RESULTS: Different bone
      healing patterns were observed according to the type of implant surface 2 weeks
      after installation; newly formed bone continuously lined the entire surfaces in
      specimens of the FAMI and SLAI groups, whereas bony trabecula from adjacent bone
      tissue appeared with minimal new bone lining onto the surface in the MI, AMI, and
      OAMI groups. Histometric results revealed a significant reduction in the BIC in
      MI, AMI, and OAMI compared to SLAI, but FAMI demonstrated a comparable BIC with
      SLAI. Although both the BIC and bone density increased from a 2- to 4-week
      healing period, bone density showed no significant difference among any of the
      experimental and control groups. CONCLUSIONS: A fibronectin-coated implant
      surface designed for cell adhesion could increase contact osteogenesis in the
      early bone healing phase, but an oxysterol-coated implant surface designed for
      osteoinductivity could not modify early bone healing around implants in normal
      bone physiology.

PMID- 25368815
TI  - Long-term results of new deproteinized bovine bone material in a maxillary sinus
      graft procedure.
AB  - PURPOSE: The aim of this case report is to present the longitudinal results of
      sinus grafting using a new demineralized bovine bone material (DBBM) in human
      cases. METHODS: A patient with a resorbed maxilla was treated by maxillary sinus
      grafting using a new deproteinized bovine bone material. After a healing period
      of 6.5 months, three implants were placed and restored. The patient was
      periodically recalled and followed up for 5 years after restoration. RESULTS:
      Twelve partially edentulous patients (average age, 55.7 years) were followed up.
      All patients had insufficient residual height in their maxillary posterior area
      and underwent maxillary sinus graft surgery to increase the height of their
      maxilla. In all, 27 fixtures were placed in the augmented bone area. On average,
      8.6 months later, implants were loaded using provisional or final restorations.
      The observation period ranged from 27 to 75 months (average, 43.3 months), and
      the patients did not show any severe resorption of the graft material or any
      infection during this time. CONCLUSIONS: Our results show that the new DBBM is
      useful for a maxillary sinus graft procedure. Good healing responses as well as
      reliable results were obtained for an average follow-up period of 43.3 months.

PMID- 25368816
TI  - Cancer cytogenetics: methodology revisited.
AB  - The Philadelphia chromosome was the first genetic abnormality discovered in
      cancer (in 1960), and it was found to be consistently associated with CML. The
      description of the Philadelphia chromosome ushered in a new era in the field of
      cancer cytogenetics. Accumulating genetic data have been shown to be intimately
      associated with the diagnosis and prognosis of neoplasms; thus, karyotyping is
      now considered a mandatory investigation for all newly diagnosed leukemias. The
      development of FISH in the 1980s overcame many of the drawbacks of assessing the
      genetic alterations in cancer cells by karyotyping. Karyotyping of cancer cells
      remains the gold standard since it provides a global analysis of the
      abnormalities in the entire genome of a single cell. However, subsequent
      methodological advances in molecular cytogenetics based on the principle of FISH
      that were initiated in the early 1990s have greatly enhanced the efficiency and
      accuracy of karyotype analysis by marrying conventional cytogenetics with
      molecular technologies. In this review, the development, current utilization, and
      technical pitfalls of both the conventional and molecular cytogenetics approaches
      used for cancer diagnosis over the past five decades will be discussed. 

PMID- 25368817
TI  - CD34 and p53 immunohistochemical stains differentiate hypocellular
      myelodysplastic syndrome (hMDS) from aplastic anemia and a CD34
      immunohistochemical stain provides useful survival information for hMDS.
AB  - BACKGROUND: The presence of significant dysplasia in bone marrow (BM) aspirates
      helps to distinguish between hypocellular myelodysplastic syndrome (hMDS) and
      aplastic anemia (AA). Occasionally, diluted BM aspirates make it difficult to
      recognize dysplastic changes and can also negatively affect the detection of
      cytogenetic abnormalities in hMDS. We evaluated the usefulness of CD34 and p53
      immunoreactivity for discriminating between hMDS and AA and for estimating
      survival outcomes in hMDS patients. METHODS: BM clot section (BMC) or BM biopsy
      (BMB) specimens were obtained from 64 hMDS/AA patients (33 with hMDS and 31 with
      AA) and seven controls. Immunohistochemical (IHC) staining for CD34 and p53 was
      performed by using the EnVision detection system (Dako, Denmark). We compared the
      results of IHC staining, BM findings, and chromosomal analyses, and determined
      overall survival outcomes. RESULTS: The number of CD34- and p53-positive BM cells
      was higher among the patients with hMDS than among the patients with AA (P<0.001
      and P=0.001, respectively). hMDS patients with increased CD34-positive cells had
      significantly poorer survival outcomes compared with those with normal number of
      CD34-positive cells (P=0.013). CONCLUSIONS: CD34 and p53 IHC stains of BMC or BMB
      provide useful information for differentiating between hMDS and AA. CD34 IHC
      staining of BMC or BMB also provides useful information for estimating survival
      outcomes in hMDS patients.

PMID- 25368818
TI  - Correlation of ciprofloxacin resistance with the AdeABC efflux system in
      Acinetobacter baumannii clinical isolates.
AB  - BACKGROUND: Acinetobacter baumannii is one of the most important pathogens
      capable of colonization in burn patients, leading to drug-resistant wound
      infections. This study evaluated the distribution of the AdeABC efflux system
      genes and their relationship to ciprofloxacin resistance in A. baumannii isolates
      collected from burn patients. METHODS: A total of 68 A. baumannii clinical
      strains were isolated from patients hospitalized in Motahari Burns Center in
      Tehran, Iran. Ciprofloxacin susceptibility was tested by the disk diffusion and
      agar dilution methods. PCR amplification of the adeRS-adeB drug efflux genes was
      performed for all resistant and susceptible isolates. To assess the role of the
      drug efflux pump in ciprofloxacin susceptibility, carbonyl cyanide 3
      chlorophenylhydrazone (CCCP) was used as an efflux pump inhibitor (EPI). RESULTS:
      Approximately 95.6% of the Acinetobacter isolates were resistant to
      ciprofloxacin, with minimum inhibitory concentration (MIC) values ranging from 4
      to >=128 ug/mL. The susceptibility of 86.1% of the resistant isolates increased
      by factors of 2 to 64 in the presence of CCCP. All resistant isolates were
      positive for the adeRS-adeB genes, and 73.2% of them had mutations in the AdeRS
      regulatory system. CONCLUSIONS: The results showed that AdeABC genes are common
      in A. baumannii, which might be associated with ciprofloxacin non-susceptibility,
      as indicated by the observed linkage to the presence of the genes essential for
      the activity of the AdeABC, several single mutations occurring in the adeRS
      regulatory system, and an increase of ciprofloxacin susceptibility in the
      presence of a CCCP EPI.

PMID- 25368819
TI  - Comparison of supplemented Brucella agar and modified Clostridium difficile agar
      for antimicrobial susceptibility testing of Clostridium difficile.
AB  - BACKGROUND: Antimicrobial susceptibility testing (AST) of Clostridium difficile
      is increasingly important because of the rise in resistant strains. The standard
      medium for the AST of C. difficile is supplemented Brucella agar (sBA), but we
      found that the growth of C. difficile on sBA was not optimal. Because active
      growth is critical for reliable AST, we developed a new, modified C. difficile
      (mCD) agar. C. difficile grew better on mCD agar than on sBA. METHODS: C.
      difficile isolates were collected from patients with healthcare-associated
      diarrhea. sBA medium was prepared according to the CLSI guidelines. Homemade mCD
      agar containing taurocholate, L-cysteine hydrochloride, and 7% horse blood was
      used. For 171 C. difficile isolates, we compared the agar dilution AST results
      from mCD agar with those from sBA. RESULTS: No significant differences were
      observed in the 50% minimal inhibitory concentration (MIC50) and 90% minimal
      inhibitory concentration (MIC90) of clindamycin (CLI), metronidazole (MTZ),
      moxifloxacin (MXF), piperacillin-tazobactam (PTZ), and rifaximin (RIX), but the
      values for vancomycin (VAN) were two-fold higher on mCD agar than on sBA. The
      MICs of CLI, MXF, and RIX were in 100% agreement within two-fold dilutions, but
      for MTZ, VAN, and PTZ, 13.7%, 0.6%, and 3.1% of the isolates, respectively, were
      outside the acceptable range. CONCLUSIONS: The MIC ranges, MIC50 and MIC90, were
      acceptable when AST was performed on mCD agar. Thus, mCD agar could be used as a
      substitute medium for the AST of C. difficile.

PMID- 25368820
TI  - Evaluation of PCR-reverse blot hybridization assay, REBA Sepsis-ID test, for
      simultaneous identification of bacterial pathogens and mecA and van genes from
      blood culture bottles.
AB  - BACKGROUND: The aim of this study was to evaluate a newly developed PCR-based
      reverse blot hybridization assay (PCR-REBA), REBA Sepsis-ID (M&D, Wonju, Korea),
      to rapidly detect the presence of bacteremia and antimicrobial resistance gene in
      blood culture samples. METHODS: One thousand four hundred consecutive blood
      culture samples from patients with a delta neutrophil index greater than 2.7%
      were selected from March to July in 2013. Three hundred positive and 1,100
      negative for bacterial growth in blood culture bottles samples were tested by
      conventional and real-time PCR-REBA, respectively. RESULTS: The overall agreement
      between the conventional identification test and the REBA Sepsis-ID test was
      95.3% (286/300). Agreement for gram-positive bacteria, gram-negative bacteria,
      fungi, and polymicrobials was 94.5% (190/201), 97.3% (71/73), 100% (14/14), and
      91.7% (11/12), respectively. The detection rate of the mecA gene from methicillin
      resistant Staphylococcus isolates was 97.8% (90/92). The vanA gene was detected
      in one blood culture sample from which vancomycin-resistant Enterococcus was
      isolated. When the cycle threshold for real-time PCR was defined as 30.0, 2.4%
      (26/1,100) of negative blood culture samples tested positive by real-time PCR.
      CONCLUSIONS: The REBA Sepsis-ID test is capable of simultaneously and quickly
      detecting both causative agents and antimicrobial resistance genes, such as mecA
      and van, in blood culture positive samples.

PMID- 25368821
TI  - Standardization of ABO antibody titer measurement at laboratories in Korea.
AB  - BACKGROUND: Measurement of the ABO antibody (Ab) titer is important in ABO
      incompatible transplantation. However, to the best of our knowledge, no standard
      protocol or external survey program to measure the ABO Ab titer has been
      established in Korea. We investigated the current status of ABO Ab titer
      measurements at various laboratories in Korea and the impact of the protocol
      provided to reduce interlaboratory variations in the methods and results of ABO
      Ab titers. METHODS: The Korean external quality assessment of blood bank
      laboratories sent external survey samples with a questionnaire to 68 laboratories
      across Korea for the measurement of ABO Ab titers in May 2012. After 6 months, a
      second set of survey samples were sent with a standard protocol to 53 of the
      previously surveyed laboratories. The protocol recommended incubation at room
      temperature only and use of the indirect antihuman globulin method for the tube
      test as well as and the column agglutination test (CAT). RESULTS: Several
      interlaboratory variations were observed in the results, technical procedures,
      and methods selected for measurement. We found that 80.4% laboratories hoped to
      change their protocol to the provisional one. Additionally, CAT showed
      significantly lower variation among laboratories (P=0.006) than the tube test.
      CONCLUSIONS: Our study provides baseline data regarding the current status of ABO
      Ab titer measurement in Korea. The standard protocol and external survey were
      helpful to standardize the technical procedures and select methods for ABO Ab
      titer measurement.

PMID- 25368822
TI  - A case of salivary-type amylase-producing multiple myeloma presenting as
      mediastinal plasmacytoma and myelomatous pleural effusion.

PMID- 25368823
TI  - A case of refractory thrombocytopenia with 5q deletion: myelodysplastic syndrome
      mimicking idiopathic thrombocytopenic purpura.

PMID- 25368824
TI  - A rare case of polycythemia vera following acute undifferentiated leukemia
      remission.

PMID- 25368825
TI  - The Sysmex XN-2000 hematology autoanalyzer provides a highly accurate platelet
      count than the former Sysmex XE-2100 system based on comparison with the
      CD41/CD61 immunoplatelet reference method of flow cytometry.

PMID- 25368826
TI  - A cryptic ETV6/ABL1 rearrangement represents a unique fluorescence in situ
      hybridization signal pattern in a patient with B acute lymphoblastic leukemia.

PMID- 25368827
TI  - The first Korean case of childhood acute myeloid leukemia with
      inv(11)(p15q22)/NUP98-DDX10 rearrangement: a rare but recurrent genetic
      abnormality.

PMID- 25368828
TI  - First report of neutrophil involvement of exflagellated Plasmodium vivax
      microgametes.

PMID- 25368829
TI  - First Korean case of Helcococcus kunzii bacteremia in a patient with diabetes.

PMID- 25368830
TI  - Discovery of a fluoroquinolone-resistant Serratia marcescens clinical isolate
      without quinolone resistance-determining region mutations.

PMID- 25368831
TI  - Surgical treatment planning for the two subtypes of mandibular asymmetry.

PMID- 25368832
TI  - Drug holiday as a prognostic factor of medication-related osteonecrosis of the
      jaw.
AB  - OBJECTIVES: To identify post-treatment prognostic factors for medication-related
      osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: We evaluated 54 MRONJ
      patients who visited the Department of Dentistry, Ajou University Hospital, from
      May 2007 to March 2014. Twenty-one patients were surgically managed with
      debridement or sequestrectomy and 33 patients were conservatively managed using
      antibiotics. Correlations of age, sex, stage, bisphosphonate duration and type,
      and drug holiday with the prognosis of MRONJ were investigated. Correlations were
      verified by logistic regression analysis and t-tests with a significance level of
      0.05. RESULTS: Clinical outcomes were evaluated on the basis of both clinical and
      radiographic findings. Twelve out of 21 surgically managed patients showed a
      favorable prognosis and nine patients relapsed. Thirty-one of the 33
      conservatively managed patients showed no specific change in prognosis, and two
      patients worsened. Statistical analyses of the conservative management group did
      not reveal any correlation of the above factors with the prognosis of
      conservative management. Drug holiday was the only prognostic factor in the
      surgical management group (P=0.031 in logistic regression analysis, P=0.004 in t
      test). CONCLUSION: Drug holiday is a prognostic factor in the surgical management
      of MRONJ. Because the drug holiday in the patients of the poor prognosis group
      occurred 1.5 to 4 months prior to surgical management, we recommend a drug
      holiday more than 4 months before surgery.

PMID- 25368833
TI  - Elective tracheostomy scoring system for severe oral disease patients.
AB  - OBJECTIVES: The purpose of this research was to create a scoring system that
      provides comprehensive assessment of patients with oromaxillofacial cancer or
      odontogenic infection, and to statistically reevaluate the results in order to
      provide specific criteria for elective tracheostomy. MATERIALS AND METHODS: All
      patients that had oral cancer surgery (group A) or odontogenic infection surgery
      (group B) during a period of 10 years (2003 to 2013) were subgrouped according to
      whether or not the patient received a tracheostomy. After a random sampling
      (group A: total of 56, group B: total of 60), evaulation procedures were observed
      based on the group classifications. For group A, four factors were evaluated: TNM
      stage, reconstruction methods, presence of pathologic findings on chest posterior
      anterior (PA), and the number of systemic diseases. Scores were given to each
      item based on the scoring system suggested in this research and the scores were
      added together. Similarly, the sum score of group B was counted using 5
      categories, including infection site, C-reactive protein level on first visit,
      age, presence of pathologic findings on chest PA, and number of systemic
      diseases. RESULTS: The scoring system rendered from this research shows that
      there is a high correlation between the scores and TNM stage in oral cancer
      patients, or infection sites in odontogenic infection patients. However, no
      correlation between pathologic findings on chest PA could be found in either
      group. The results also indicated that for both groups, the hospital day
      increased with the tracheostomy score. The tracheostomy score cutoff value was 5
      in oral cancer patients and 6 in odontogenic infection patients which was used
      for elective tracheostomy indication. CONCLUSION: The elective tracheostomy score
      system suggested by this research is a method that considers both the surgical
      and general conditions of the patient, and can be very useful for managing
      patients with severe oral disease.

PMID- 25368835
TI  - Characteristics of bony changes and tooth displacement in the mandibular cystic
      lesion involving the impacted third molar.
AB  - OBJECTIVES: The purpose of this retrospective study is to find the
      differentiating characteristics of cystic and cystic-appearing lesions that
      involve the impacted mandibular third molar by analyzing panoramic radiographs
      and computed tomography images, and to aid the preoperative diagnosis. MATERIALS
      AND METHODS: Eighty-one patients who had a mandibular cystic or cystic-appearing
      lesion that involved impacted mandibular third molar and underwent cyst
      enucleation were included in the study. The preoperative panoramic radiograph and
      computed tomography findings were analyzed in accordance to the histopathologic
      type. RESULTS: Most of the cystic lesions containing the mandibular third molar
      were diagnosed as a dentigerous cyst (77.8%). The occurrence of mesio-distal
      displacement of the third molar was more frequent in the odontogenic keratocyst
      (71.4%) and in the ameloblastoma (85.7%) than in the dentigerous cyst (19.1%).
      Downward displacement was primarily observed in each group. Odontogenic
      keratocyst and ameloblastoma showed more aggressive growth pattern with higher
      rate of bony discontinuity and cortical bone expansion than in dentigerous cyst.
      CONCLUSION: When evaluating mandibular cystic lesions involving the impacted
      mandibular third molar, dentigerous cyst should first be suspected. However, when
      the third molar displacement and cortical bone absorption are observed, then
      odontogenic keratocyst or ameloblastoma should be considered.

PMID- 25368834
TI  - Assessment of interleukin-1beta and interleukin-6 in the crevicular fluid around
      healthy implants, implants with peri-implantitis, and healthy teeth: a cross
      sectional study.
AB  - OBJECTIVES: This study aimed to assess and compare the levels of interleukin
      1beta (IL-1beta) and interleukin-6 (IL-6) in the crevicular fluid around healthy
      implants, implants with peri-implantitis, and healthy teeth. MATERIALS AND
      METHODS: This study evaluated 16 dental implants in 8 patients (4 males and 4
      females). These patients had at least one healthy implant and one implant with
      peri-implantitis next to healthy teeth. The crevicular fluid was collected using
      absorbent cones and transferred to the laboratory. Specimens were evaluated by
      ELISA for interleukin levels. Data were analyzed using repeated measures ANOVA
      and Bonferroni tests (P<0.05). RESULTS: Levels of IL-1beta in the crevicular
      fluid around implants with peri-implantitis were significantly higher than around
      healthy implants (P=0.002); the latter was significantly higher than around
      healthy teeth (P=0.015). A significant difference was found in the level of IL-6
      in the crevicular fluid around implants with peri-implantitis and healthy
      implants (P=0.049) and also between implants with peri-implantitis and healthy
      teeth (P<0.001). CONCLUSION: Within the limitations of this study, significant
      differences exist in the levels of IL-1beta and IL-6 in the crevicular fluid of
      implants with peri-implantitis, healthy implants, and healthy teeth. More studies
      with larger sample sizes in different populations are necessary.

PMID- 25368836
TI  - Horizontal ridge expansion and implant placement using screws: a report of two
      cases.
AB  - Implants are typically placed after performing ridge expansion by inserting
      screws of gradually increasing thickness and good clinical outcomes are often
      obtained. We placed 11 implants in 6 patients, and one implant failed during
      osseointegration but it was replaced immediately after removal and successful
      prosthetic treatments were completed. During these surgeries, buccal cortical
      plate complete fractures do not occur. Inserting screws for ridge expansion is a
      successful and predictable technique for implant placement in narrow alveolar
      bone. 

PMID- 25368837
TI  - Angiokeratoma circumscriptum of the buccal mucosa: a case report and literature
      review.
AB  - Angiokeratoma is a benign cutaneous lesion of the capillaries, presenting as
      dilated vessels in the upper part of the dermis. Although this disorder is
      classified into various types and has been occasionally reported in the skin of
      the scrotum or extremities, the involvement of the oral cavity mucosa has been
      rarely reported. The present study reports a case of angiokeratoma circumscriptum
      in the buccal mucosa. The expression of vascular endothelial growth factor (VEGF)
      and both of its receptors (VEGFR-1 and VEGFR-2) was demonstrated by
      immunohistochemistry in the endothelial cells lining the dilated vessels. The
      expression of VEGFR-2 was higher than that of VEGFR-1 in the endothelial cells in
      the lesion, indicating an increased rate of endothelial cell proliferation within
      the lesion. Interestingly, some of the endothelial cells co-expressed VEGF and
      its two receptors. These results suggest that endothelial cells in the
      pathologically dilated vessels possess VEGF autocrine growth activity involved in
      vasculogenesis and maintenance in angiokeratoma lesions. To our knowledge, this
      is the second report published on isolated oral angiokeratoma confined to the
      buccal mucosa and the first case report on angiokeratoma circumscriptum involving
      the buccal mucosa. 

PMID- 25368838
TI  - Nonsurgical treatment of stylohyoid (Eagle) syndrome: a case report.
AB  - Eagle syndrome is a rare condition caused by elongation of the styloid process or
      calcification of the stylohyoid ligament. Patients with Eagle syndrome typically
      present with dysphagia, dysphonia, cough, voice changes, otalgia, sore throat,
      facial pain, foreign body sensation, headache, vertigo, and neck pain. Here we
      report a case in which the patient initially presented with sore throat, left
      sided facial pain, and cough. This case report provides a brief review of the
      diagnosis and nonsurgical management of this rare syndrome. 

PMID- 25368839
TI  - A simple method of intraoperative intubation tube change.
AB  - Nasotracheal intubation should be performed in patients with jaw fractures
      because maxillomandibular fixation is required. However, when there are
      concomitant fractures of the nose and facial bones, an intubation tube positioned
      at the nose makes it difficult to perform an intricate surgery. In order to
      overcome these problems, a variety of ways to change the position of the tube
      have been introduced. We describe a simple technique of switching the tube from a
      nasal to oral position, which was easily executed in a patient with concomitant
      nasal and mandibular fractures, accompanied by a literature review. 

PMID- 25368840
TI  - Adenoid cystic carcinoma presenting as an ulcer on the floor of the mouth: a rare
      case report.
AB  - Adenoid cystic carcinoma is a rare epithelial tumour, and comprises about 1% of
      all malignant tumours of the oral and maxillofacial region. It is a malignant
      tumour which may develop in the trachea, bronchus, lungs or mammary glands, in
      addition to the head and neck region. Occurrences in the head and neck are mostly
      detected in the major salivary gland, oral cavity, pharynx and paranasal sinus
      where it presents as a slow growing firm nodular swelling. The aim of the article
      is to highlight the unique presentation of adenoid cystic carcinoma as a solitary
      ulcer on the floor of the mouth. 

PMID- 25368842
TI  - Evidence of differential effects of vitamin d receptor variants on epithelial
      ovarian cancer risk by predicted vitamin d status.
AB  - INTRODUCTION: Experimental studies suggest vitamin D inhibits ovarian
      carcinogenesis. Yet, epidemiologic studies of ovarian cancer risk and lifestyle
      correlates of vitamin D status, plasma 25-hydroxyvitamin D [25(OH)D], or vitamin
      D receptor (VDR) variants have been inconsistent. OBJECTIVE: To evaluate VDR
      genetic associations by high vs. low predicted 25(OH)D, scores derived from known
      determinants of plasma 25(OH)D. To assess ovarian cancer associations with
      variants identified in genome-wide association studies (GWAS) of plasma 25(OH)D.
      METHODS: We genotyped up to seven VDR and eight 25(OH)D GWAS variants in the
      Nurses' Health Studies (562 cases, 1,553 controls) and New England Case-Control
      study (1,821 cases, 1,870 controls). We estimated haplotype scores using
      expectation-maximization-based algorithms. We used unconditional logistic
      regression to calculate odds ratios (ORs) and 95% confidence intervals (CI). We
      combined study results using DerSimonian and Laird meta-analysis. RESULTS:
      Ovarian cancer risk increased per A allele of rs7975232 (VDR; OR = 1.12, 95% CI =
      1.01-1.25) among all women. When stratified by predicted 25(OH)D, ovarian cancer
      was associated with rs731236 (VDR; per C allele OR = 1.31) and rs7975232 (OR =
      1.38) among women with high predicted 25(OH)D, but not among women with low
      levels (P <= 0.009). We also observed heterogeneity by predicted 25(OH)D for the
      ovarian cancer association with VDR 3' end haplotypes (P = 0.009). Of 25(OH)D
      associated GWAS loci, rs7041 was associated with reduced ovarian cancer risk (per
      T allele OR = 0.92, 95% CI = 0.85-0.99), which did not differ by predicted
      25(OH)D status. CONCLUSION: Our study suggests an influence of VDR 3' end
      variants on ovarian cancer risk may be observed in women with high predicted
      25(OH)D, which remained even after taking multiple comparisons into
      consideration. Future studies are needed to confirm our results and explore
      further the relation between vitamin D exposure, genetic variants, and ovarian
      cancer risk.

PMID- 25368843
TI  - Stereotactic body radiation therapy for stage I non-small cell lung cancer: a
      small academic hospital experience.
AB  - PURPOSE/OBJECTIVE(S): Stereotactic body radiation therapy (SBRT) has been shown
      to have increased local control and overall survival relative to conventional
      external beam radiation therapy in patients with medically inoperable stage I non
      small cell lung cancer (NSCLC). Excellent rates of local control have been
      demonstrated both in clinical trials and in single-center studies at large
      academic institutions. However, there is limited data on the experiences of small
      academic hospitals with SBRT for stage I NSCLC. The purpose of this study is to
      report the local control and overall survival rates in patients treated with SBRT
      for stage I NSCLC at Winthrop-University Hospital (WUH), a small academic
      hospital. MATERIALS/METHODS: This is a retrospective review of 78 stage I central
      and peripheral NSCLC tumors treated between December 2006 and July 2012 with SBRT
      at WUH. Treatment was given utilizing fiducials and a respiratory tracking
      system. If the fiducials were not trackable, a spine tracking system was used for
      tumor localization. CT-based planning was performed using the ray trace
      algorithm. Treatment was delivered over consecutive days to a median dose of 4800
      cGy delivered in four fractions. The Kaplan-Meier method was used to calculate
      local control and overall survival. RESULTS: The median age was 78.5 years. Fifty
      four percent of the patient population was female. Sixty seven percent of the
      tumors were stage IA, and 33% of the tumors were stage IB. Fifty-three percent of
      the tumors were adenocarcinomas and 29% were squamous cell carcinomas, with the
      remainder being of unknown histology or NSCLC, not otherwise specified The 2-year
      local control rate was 87%, and the 2-year overall survival was 68%. CONCLUSION:
      Our findings support that local control and overall survival at a small academic
      hospital are comparable to that of larger academic institutions' published
      experiences with SBRT for stage I NSCLC.

PMID- 25368844
TI  - The war on cancer: lessons from the war on terror.

PMID- 25368846
TI  - Cystoscopic-assisted partial cystectomy: description of technique and results.
AB  - BACKGROUND: Partial cystectomy provides oncological results comparable with those
      of radical cystectomy in selected patients with invasive bladder cancer without
      the morbidity associated with radical cystectomy and urinary diversion. We
      describe a novel technique of partial cystectomy that allows accurate
      identification of tumor margins while minimizing damage to the rest of the
      bladder. METHODS: During the study period, 30 patients underwent partial
      cystectomy for invasive high-grade cancer. In 19 patients, the traditional method
      of tumor identification was used, ie, identifying the tumor by palpation and
      cystotomy. In eleven patients, after mobilization of the bladder, flexible
      cystoscopy was done and the light of the cystoscope was pointed toward one edge
      of the planned resected ellipse around the tumor, thus avoiding cystotomy.
      RESULTS: Patients who underwent partial cystectomy using the novel method were
      similar in all characteristics to patients operated on using the traditional
      technique except for tumor diameter which was significantly larger in patients
      operated on using the novel method (4.3+/-1.5 cm versus 3.11+/-1.18 cm, P=0.032).
      Complications were rare in both types of surgery. The 5-year local recurrence
      free survival was marginally superior using the novel method (0.8 versus 0.426,
      P=0.088). Overall, disease-specific and disease-free survival rates were similar.
      CONCLUSION: The use of a flexible cystoscope during partial cystectomy is a
      simple, low-cost maneuver that assists in planning the bladder incision and
      minimizes injury to the remaining bladder by avoiding the midline cystotomy.
      Initial oncological results show a trend toward a lower rate of local recurrence
      compared with the standard method.

PMID- 25368845
TI  - Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae.
AB  - Deciphering the principles how pathogenic bacteria adapt their metabolism to a
      specific host microenvironment is critical for understanding bacterial
      pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis
      and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis,
      are able to survive in a large variety of environmental reservoirs (e.g., soil,
      plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans)
      with a particular preference for lymphatic tissues. In order to manage rapidly
      changing environmental conditions and interbacterial competition, Yersinia senses
      the nutritional composition during the course of an infection by special
      molecular devices, integrates this information and adapts its metabolism
      accordingly. In addition, nutrient availability has an impact on expression of
      virulence genes in response to C-sources, demonstrating a tight link between the
      pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed
      that global regulatory factors such as the cAMP receptor protein (Crp) and the
      carbon storage regulator (Csr) system are part of a large network of
      transcriptional and posttranscriptional control strategies adjusting metabolic
      changes and virulence in response to temperature, ion and nutrient availability.
      Gained knowledge about the specific metabolic requirements and the correlation
      between metabolic and virulence gene expression that enable efficient host
      colonization led to the identification of new potential antimicrobial targets. 

PMID- 25368848
TI  - Comparison of putative circulating cancer stem cell detection between the hepatic
      portal system and peripheral blood in colorectal cancer patients.
AB  - PURPOSE: The present pilot study was conducted to detect putative cancer stem
      cell (CSC) from the hepatic portal system and peripheral blood in the colorectal
      cancer patients and to compare them to healthy donor and diverticulitis patients.
      METHODS: Laboratory study was performed to identify the expression of cell
      surface markers, epithelial cell adhesion molecule (EpCAM), cytokeratin (CK) 18,
      CK20, CD44, and CD133, on several colon cancer cell lines. Clinical pilot study
      was conducted to detect putative circulating CSC as EpCAM(+)CD133(+) cell in
      colorectal cancer (n = 10), diverticulitis (n = 5), and four healthy donors, by
      using flow cytometry. Blood was drawn from the hepatic portal system and
      peripheral vein. RESULTS: On laboratory study, EpCAM was expressed in whole colon
      cancer cell lines, and CD44 and CD133 were simultaneously expressed in 50% of the
      cell lines with stemness phenotype, but CK18 and CK20 were not expressed in most
      of the cell lines. On clinical study, the mean EpCAM(+)CD133(+) cell counts of
      11.6/10(5) in the hepatic portal system were somewhat lower than 15.4/10(5) in
      peripheral vein (P = 0.241). As for diverticulitis patients, EpCAM(+)CD133(+)
      cells were also detected to have steeper dropped to near zero, after the surgery.
      CONCLUSION: The numbers of putative CSC were not statistically different between
      the detection sites of the portal vein and peripheral vein in the colon cancer
      patients. Therefore, we may not have benefitted by getting the cells from the
      hepatic portal system. In addition, the CD133(+)EpCAM(+) cells in the colon
      cancer patients might contain normal stem cells from cancer inflammation similar
      to diverticulitis.

PMID- 25368847
TI  - The distance of proximal resection margin dose not significantly influence on the
      prognosis of gastric cancer patients after curative resection.
AB  - PURPOSE: It is well known that the curative resection with an adequate proximal
      margin length is the most effective treatment in gastric cancer. However, despite
      surgeon's effort to achieve a sufficient proximal margin length, it is often
      difficult to obtain a recommended proximal margin length in some cases.
      Therefore, this study was planned to investigate the impact of the length of
      proximal margin on prognosis of overall survival. METHODS: Between June 1992 and
      December 2010, 1,888 gastric cancer patients who underwent gastrectomy with
      curative intent were reviewed. According to tumor's location (total vs. subtotal
      gastrectomy), pathologic T staging, and differentiation, univariate and
      multivariate analyses were performed to evaluate the impact of the discrepancies
      of proximal margin length on overall survival. Also, the impact of the
      discrepancies of proximal margin length on local recurrence was assessed.
      RESULTS: The 5-year survival rate of positive proximal margin group was 5.9%. In
      negative proximal margin groups, multivariate analysis showed that the
      discrepancies of proximal margin length have no impact on overall survival.
      Kaplan-Meier analyses showed that there is no association between discrepancy of
      proximal margin length and local recurrence. CONCLUSION: It takes effort to
      secure a negative proximal margin in the surgical treatment of gastric cancer
      because of the poor prognosis of positive proximal margin. In negative proximal
      margin patients, there's no need to achieve an additional proximal margin length
      for long-term survival benefit because there was no impact of proximal margin
      length on overall survival and local recurrence.

PMID- 25368849
TI  - Increasing utilization of abdominal CT in the Emergency Department of a secondary
      care center: does it produce better outcomes in caring for pediatric surgical
      patients?
AB  - PURPOSE: The use of abdominal computed tomography (ACT) utilization is increasing
      to a remarkable extent in the pediatric Emergency Department (ED), but the
      clinical benefit of increased use of ACT for pediatric surgical patients remains
      uncertain. METHODS: A retrospective review was conducted to investigate if, for
      patients who had visited pediatric ED during the last 5 years, increasing
      utilization of ACT would increase the detection rate of acute appendicitis,
      increase the detection rate of surgical conditions other than appendicitis, and
      decrease the hospital admission rate for surgical conditions. RESULTS: During the
      study period, there were 37,918 ED visits; of these, 3,274 (8.6%) were for
      abdominal pain, 844 (2.2%) had ACT performed. The annual proportional increase of
      the ACT was statistically significant (1.56% to 2.46%, P = 0.00), but the
      detection rate of acute appendicitis (3.3% to 5.1%) or other surgical conditions
      (1.7% to 2.8%) showed no statistically significant changes. Hospital admission
      rates (5.6% to 6.8%) also showed no significant changes during the study period.
      CONCLUSION: Increasing utilization of ACT does not lead to the improved outcomes
      in caring for pediatric surgical patients visiting the pediatric ED. Careful
      evaluation for the indication for ACT is needed in the pediatric ED.

PMID- 25368851
TI  - Management of neck contractures by single-stage dermal substitutes and skin
      grafting in extensive burn patients.
AB  - PURPOSE: Severe neck contracture is a problem that must be resolved by priority.
      We consider the best contracture treatment to be the full-thickness skin graft.
      However, clinicians often encounter patients, especially extensive burn patients,
      who have insufficient donor sites for the full-thickness skin graft. We treated
      extensive burn patients with neck scar contractures with a split-thickness skin
      graft (STSG) combined with dermal substitutes. The purpose of this study was to
      evaluate clinical outcomes of neck contracture treatment in extensive burn
      patients performing STSG with dermal substitutes as adjuvant treatment. METHODS:
      We analyzed the retrospective clinical and photographic records of 28 patients
      with severe neck contracture who were admitted to Hallym University Hangang
      Sacred Heart Hospital, Seoul, Korea, from January 2012 to December 2012. We
      performed STSG in combination with dermal substitutes to minimize the degree of
      contracture. RESULTS: The overall take rate of skin to dermal substitutes was
      95.9%, and no grafts failed to affect recontracture except in one patient with a
      partial loss of artificial dermis who underwent a follow-up skin graft without
      any problems. Excellent/good outcomes were shown in 27 out of 28 patients.
      CONCLUSION: In extensive burn patients, skin grafting in combination with dermal
      substitutes can be an alternative to STSG alone for contracture release.

PMID- 25368852
TI  - Vacuum-assisted close versus conventional treatment for postlaparotomy wound
      dehiscence.
AB  - PURPOSE: The conventional treatment for postlaparotomy wound dehiscence usually
      involves surgical revision. Recently, vacuum-assisted closure has been
      successfully used in postlaparotomy wound dehiscence. The aim of the present
      study was to compare the clinical outcome of 207 patients undergoing vacuum
      assisted closure therapy or conventional treatment for postlaparotomy wound
      dehiscence. METHODS: TWO HUNDRED AND SEVEN CONSECUTIVE PATIENTS UNDERWENT
      TREATMENT FOR POSTLAPAROTOMY WOUND DEHISCENCE: vacuum-assisted closure therapy
      (January 2007 through August 2012, n = 25) or conventional treatment (January
      2001 through August 2012, n = 182). RESULTS: The failure rate to first-line
      treatment with vacuum-assisted closure and conventional treatment were 0% and
      14.3%, respectively (P = 0.002). There was no statistically significant
      difference in the enterocutaneous fistulas and hospital stay after vacuum
      assisted closure therapy or conventional treatment respectively. CONCLUSION: Our
      findings support that vacuum-assisted closure therapy is a safe and reliable
      option in postlaparotomy wound dehiscence with very low failure rate in surgical
      revision compared with conventional treatment.

PMID- 25368850
TI  - The comparison of monitored anesthesia care with dexmedetomidine and spinal
      anesthesia during varicose vein surgery.
AB  - PURPOSE: The purpose of this study was to investigate the effectiveness and
      safety of monitored anesthesia care (MAC) using dexmedetomidine for its sedative
      and analgesic effect during varicose vein surgery. METHODS: Forty-two patients,
      who underwent varicose vein surgery, were divided into the MAC group (n = 20) or
      the spinal anesthesia group (n = 22) for randomized clinical trial. In the MAC
      group, dexmedetomidine was administered by a loading dose of 1 ug/kg for 10
      minutes, followed by a maintenance infusion of 0.2-1.0 ug/kg/hr. Ketamine was
      used for intermittent injection. In the spinal anesthesia group, midazolam was
      used for sedation. Intraoperative vital signs, the number of adverse events, and
      the satisfaction of patients and surgeons concerning the anesthetic condition
      were compared between the two groups. RESULTS: Systolic blood pressure was
      intraoperatively significantly different over time between the two groups. The
      groups had statistical differences in the change in heart rate with regard to
      time. In the postanesthetic care unit, patients and surgeons in the MAC group had
      a lower satisfaction score, compared to patients and surgeons in the spinal
      anesthesia group. However, in the recovery period, patients had a positive
      perception concerning MAC anesthesia. In addition, without significant adverse
      events, the MAC group had a shorter time to possible ambulation, which indicated
      an early recovery. CONCLUSION: We believe that MAC using dexmedetomidine in
      combination with ketamine may be an alternative anesthetic technique for varicose
      vein surgery with regard to a patient's preference and medical condition.

PMID- 25368853
TI  - Validation of the Korean version Moorehead-Ardelt quality of life questionnaire
      II.
AB  - PURPOSE: To investigate the weight loss effects with higher sensitivity, disease
      specific quality of life (QoL) instruments were important. The Moorehead-Ardelt
      quality of life questionnaire II (MA-II) is widely used, because it was simple
      and validated the several languages. The aims of present study was performed the
      translation of MA-II Korean version and the validation compared with EuroQol-5
      dimension (EQ-5D), obesity-related problems scale (OP-scale), and impact of
      weight quality of life-lite (IWQoL-Lite). METHODS: The study design was a
      multicenter, cross-sectional survey and this study was included the postoperative
      patients. The validation procedure is translation-back translation procedure,
      pilot study, and field study. The instruments of measuring QoL included the MA
      II, EQ-5D, OP-scale, and IWQoL-lite. The reliability was checked through internal
      consistency using Cronbach alpha coefficients. The construct validity was
      assessed the Spearman rank correlation between 6 domains of MA-II and EQ-5D, OP
      scale, and 5 domains of IWQoL-Lite. RESULTS: The Cronbach alpha of MA-II was
      0.763, so the internal consistency was confirmed. The total score of MA-II was
      significantly correlated with all other instruments; EQ-5D, OP-scale, and IWQoL
      Lite. IWQoL-lite (rho = 0.623, P < 0.001) was showed the strongest correlation
      compared with MA-II, followed by OP-scale (rho = 0.588, P < 0.001) and EQ-5D (rho
      = 0.378, P < 0.01). CONCLUSION: The Korean version MA-II was valid instrument of
      measuring the obesity-specific QoL. Through the present study, the MA-II was
      confirmed to have good reliability and validity and it was also answered simple
      for investigating. Thus, MA-II could be estimated sensitive and exact QoL in
      obesity patients.

PMID- 25368854
TI  - Polyarteritis nodosa presented as a dilatation of the intrahepatic bile duct.
AB  - Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of small- and
      medium-sized arteries in multiorgan systems. PAN may affect the gastrointestinal
      tract in 14%-65% of patients, but rarely involves the biliary tract and liver. We
      describe a patient without underlying disease who was diagnosed with PAN during
      resection of the gallbladder and liver. 

PMID- 25368855
TI  - Incidental cholecystojejunal fistula treated with successful laparoscopic
      management.
AB  - Internal biliary fistula (IBF) is occurred spontaneously due to the biliary
      disease in most cases. Bilioenteric, biliobiliary, bronchobiliary, and
      vasculobiliary type of IBF have been reported in the literature. We herein
      describe our experience with an incidental cholecystojejunal fistula, a very rare
      type of bilioenteric fistula in laparoscopic cholecystectomy. A 61-year-old woman
      with several years' history of intermittent right upper abdominal pain was
      admitted to Soonchunhyang University Cheonan Hospital. Abdominal CT scan showed
      the pneumobilia in gallbladder with common bile duct dilatation. Endoscopic
      retrograde cholangiopancreatography and endoscopic sphincterotomy were done. On
      operative findings, there was a cholecystojejunal fistula. We performed
      laparoscopic cholecystectomy and fistulectomy with jejunal partial resection. To
      our knowledge, this is the first report on incidental cholecystojejunal fistula
      uncombined with any other disease and was treated with laparoscopic procedure. 

PMID- 25368856
TI  - Pure single-incision laparoscopic D2 lymphadenectomy for gastric cancer: a novel
      approach to 11p lymph node dissection (midpancreas mobilization).
AB  - We developed a novel approach to perform a perfect 11p lymph node dissection
      (LND), the so-called 'midpancreas mobilization' (MPM) method. Briefly, in pure
      single-incision laparoscopic distal gastrectomy (SIDG), after the completion of
      7, 8a/12a, and 9 LND in the suprapancreatic portion, we started 11p LND after
      midpancreas mobilization. After mobilization of the entire midpancreas from the
      white line of Toldt, two gauzes were inserted behind the pancreas. This maneuver
      facilitated exposure of the splenic vein and complete detachment of soft tissue,
      including 11p lymph nodes, from the white line of Toldt, which was possible
      because of the tilting of the pancreas. The dissection plane along the splenic
      artery and vein for 11p LND could be visualized just through control of the
      operator's grasper without the need of an assistant. Fourteen patients underwent
      the procedure without intraoperative events, conversion to conventional
      laparoscopy, or surgery-related complications, including postoperative pancreatic
      fistula. All patients underwent D2 LND by exposure of the splenic vein. The mean
      numbers of retrieved lymph node and 11p lymph node were 61.3 +/- 9.0 (range, 49
      70), and 4.00 +/- 3.38 (range, 1-10). Thus, we concluded that MPM for 11p LND in
      pure SIDG appears feasible and embryologically ideal; this method can be used in
      conventional laparoscopic gastrectomy.

PMID- 25368857
TI  - Gestational Diabetes Independently Increases Birth Length and Augments the
      Effects of Maternal BMI on Birth Weight: A Retrospective Cohort Study.
AB  - OBJECTIVE: To investigate the effect of the interaction between gestational
      diabetes mellitus (GDM) and maternal body mass index (BMI) on the individual
      neonatal growth parameters. DESIGN: Retrospective cohort study. SETTING: A
      tertiary maternity service in Sydney, Australia, between 2005 and 2009.
      POPULATION: A cohort of 8859 women. METHODS: Generalized linear models. MAIN
      OUTCOME MEASURES: Neonatal growth parameters, represented by z-scores for infant
      birth weight (BW), birth length (BL), and head circumference (HC) in GDM and non
      GDM groups. RESULTS: Only GDM alone had an independent and positive effect on BL
      (p = 0.02) but not on BW or HC. In addition, in pregnancies complicated with GDM,
      the association between maternal weight and BW was significantly stronger (p <
      0.001). In combination, GDM and maternal BMI significantly affected z-score
      differences between BW and BL (p < 0.001), in that underweight mothers had babies
      that were lighter relative to their length and inversely obese mothers had babies
      that were heavier relative to their length. CONCLUSION: GDM independently
      influences BL and increases the association between maternal BMI and BW. In
      accordance with the hypothesis of the fetal origins of health and disease, the
      pronounced effects of GDM on fetal growth patterns demonstrated in this study are
      likely to influence long-term health outcomes in children.

PMID- 25368859
TI  - Variability of FEV1 and criterion for acute pulmonary exacerbation.

PMID- 25368858
TI  - Ventilation before Umbilical Cord Clamping Improves the Physiological Transition
      at Birth.
AB  - The transition from a fetus to a neonate at birth represents a critical phase in
      our life. Most infants make this transition without complications, but preterm
      infants usually require some form of assistance due to immature cardiopulmonary
      systems that predispose them to lifelong sequelae. As the incidence of preterm
      birth is increasing, there is now an urgent need for the development of
      management strategies that facilitate this transition, which will likely include
      improved strategies for the management of the maternal third stage of labor. For
      instance, recent studies on the physiological transition at birth have led to the
      discovery that establishing ventilation in the infant before the umbilical cord
      is clamped greatly stabilizes the cardiovascular transition at birth. While most
      benefits of delayed clamping previously have been attributed to an increase in
      placenta to infant blood transfusion, clearly there are other significant
      benefits for the infant, which are not well understood. Nevertheless, if
      ventilation can be established before cord clamping in a preterm infant, the
      large adverse changes in cardiac function that normally accompanies umbilical
      cord clamping can be avoided. As preterm infants have an immature cerebral
      vascular bed, large swings in cardiovascular function places them at high risk of
      cerebral vascular rupture and the associated increased risk of mortality and
      morbidity. In view of the impact that cord clamping has on the cardiovascular
      transition at birth, it is also time to re-examine some of the strategies used in
      the management of the third stage of labor. These include the appropriate timing
      of uterotonic administration in relation to delivery of the infant and placenta.
      As there is a lack of evidence on the effects these individual practices have on
      the infant, there is a necessity to improve our understanding of their impact in
      order to develop strategies that facilitate the transition to newborn life. 

PMID- 25368860
TI  - Young Men's Shame about Their Desire for other Men Predicts Risky Sex and
      Moderates the Knowledge - Self-Efficacy Link.
AB  - BACKGROUND: Nationally, HIV incidence is rising rapidly among young (18-24 years
      old) men who have sex with men (YMSM). Knowledge of safer sex generally enhances
      self-efficacy for safer sex, an important predictor of safer-sex behaviors.
      Recent findings suggest that a strong negative social emotion (i.e., shame)
      increases YMSM's sexual risk-taking. Unchangeable shame (e.g., desire for other
      men) might undermine (moderate) the link between knowledge and self-efficacy or
      between self-efficacy and unprotected anal intercourse (UAI): this may be less
      likely for changeable shame (e.g., shame about risky sexual behavior). AIM: To
      test the hypotheses that shame (i.e., sexual desire shame), but not shame about
      behavior (i.e., sexual behavior shame), will be positively related to UAI and
      will moderate the relationship between knowledge and self-efficacy and/or self
      efficacy and UAI among YMSM. METHOD: In an online national study, 1177 young
      adult (18-24 years old) MSM reported one or more acts of UAI in the past 90 days
      with a casual partner. Eligible MSM filled out a survey in which they provided
      information about their knowledge of safer sex, self-efficacy for safer sex,
      reported levels of shame, and reported past 90-day UAI. RESULTS: Sexual desire
      shame was negatively correlated with knowledge and self-efficacy and positively
      correlated with UAI, the pattern reversed for sexual behavior shame. Sexual
      desire shame significantly lowered the knowledge to self-efficacy and the self
      efficacy to UAI links. Sexual behavior shame also reduced the link from knowledge
      to self-efficacy, but not the self-efficacy to UAI link. CONCLUSION: The present
      study shows that there are different types of shame that may produce different
      effects with different implications for health behavior. Sexual desire shame may
      better reflect an emotion that is activated prior to risky behavior (e.g., when
      men reflect upon or feel desire for another man). Sexual behavior shame, on the
      other hand, better reflects what has already happened, thus, those higher in
      knowledge, efficacy, and therefore, safer sex are least likely to experience
      shame behavior.

PMID- 25368862
TI  - Association of household environment and prevalence of anemia among children
      under-5 in India.
AB  - OBJECTIVE: The study explores the association between the household environment
      and the prevalence of anemia among children under the age of 5 years in India.
      Data and methodology: The study is based on 52,868 children under the age of 5
      years, included in India's National Family Health Survey-3. The outcome variable
      was the prevalence of anemia. To understand the role of environment in
      determining child anemia, step wise logistic regression models consisting of
      environmental, child, socio-economic, and media exposure variables were applied.
      RESULTS: The occurrence of childhood anemia was higher in the North Eastern and
      Eastern regions compared to all other regions of India. Unclean fuel use, poor
      toilet facilities, staying in non-concrete house, exposure to smoking were
      important variables determining the prevalence of anemia. Smoking, when it was
      controlled with only socio economic factors, showed lesser impact on anemia, but
      when it got adjusted with socio-economic, child, and media variables together it
      showed an important impact as it increased the risk of anemia. CONCLUSION:
      Children under 5 years of age generally stay inside their house and are more
      exposed to the household environment. Thus, among these children there are
      multiple risk factors causing anemia along with the nutritional deficiencies.
      Better resources are needed to educate the public and to increase awareness for
      improved hygiene, sanitation and housing facilities, health and nutrition, etc.
      Along with a wider program to manage nutritional deficiency, anemia in children
      <5 years, there should be a holistic approach toward anemia control inculcating
      household environmental conditions and socio economic determinants.

PMID- 25368861
TI  - Smokeless tobacco use as a risk factor for periodontal disease.

PMID- 25368863
TI  - Novel dutch self-assessment biosecurity toolkit to identify biorisk gaps and to
      enhance biorisk awareness.

PMID- 25368864
TI  - Intellectual and developmental disabilities: eugenics.

PMID- 25368865
TI  - Epidemiology and social inequalities of periodontal disease in Brazil.

PMID- 25368866
TI  - Copper mediated controlled radical copolymerization of styrene and 2-ethylhexyl
      acrylate and determination of their reactivity ratios.
AB  - Copolymerization is an important synthetic tool to prepare polymers with
      desirable combination of properties which are difficult to achieve from the
      different homopolymers concerned. This investigation reports the copolymerization
      of 2-ethylhexyl acrylate (EHA) and styrene using copper bromide (CuBr) as
      catalyst in combination with N,N,N',N",N"- pentamethyldiethylenetriamine (PMDETA)
      as ligand and 1-phenylethyl bromide (PEBr) as initiator. Linear kinetic plot and
      linear increase in molecular weights vs. conversion indicate that
      copolymerization reactions were controlled. The copolymer composition was
      calculated using (1)H NMR studies. The reactivity ratio of styrene and EHA (r1
      and r2) were determined using the Finemann-Ross (FR), inverted Finemann-Ross
      (IFR), and Kelen-Tudos (KT) methods. Thermal properties of the copolymers were
      also studied by using TGA and DSC analysis. 

PMID- 25368868
TI  - Grand challenges in biomaterials.

PMID- 25368867
TI  - Development of second generation peptides modulating cellular adiponectin
      receptor responses.
AB  - The adipose tissue participates in the regulation of energy homeostasis as an
      important endocrine organ that secretes a number of biologically active
      adipokines, including adiponectin. Recently we developed and characterized a
      first-in-class peptide-based adiponectin receptor agonist by using in vitro and
      in vivo models of glioblastoma and breast cancer (BC). In the current study, we
      further explored the effects of peptide ADP355 in additional cellular models and
      found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and
      renal myofibroblast differentiation with mid-nanomolar IC50 values. According to
      molecular modeling calculations, ADP355 was remarkably flexible in the global
      minimum with a turn present in the middle of the peptide. Considering these
      structural features of ADP355 and the fact that adiponectin normally circulates
      as multimeric complexes, we developed and tested the activity of a linear
      branched dimer (ADP399). The dimer exhibited approximately 20-fold improved
      cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM-low nM
      relative IC50 values. Biodistribution studies suggested superior tissue
      dissemination of both peptides after subcutaneous administration relative to
      intraperitoneal inoculation. After screening of a 397-member adiponectin active
      site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000
      nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar
      concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to
      antagonizing endogenous adiponectin actions or acting as an inverse agonist.
      While the linear dimer agonist ADP399 meets pharmacological criteria of a
      contemporary peptide drug lead, the peptide showing antagonist activity (ADP400)
      at similar concentrations will be an important target validation tool to study
      adiponectin functions. 

PMID- 25368869
TI  - Enhancing stress-resistance for efficient microbial biotransformations by
      synthetic biology.
AB  - Chemical conversions mediated by microorganisms, otherwise known as microbial
      biotransformations, are playing an increasingly important role within the
      biotechnology industry. Unfortunately, the growth and production of
      microorganisms are often hampered by a number of stressful conditions emanating
      from environment fluctuations and/or metabolic imbalances such as high
      temperature, high salt condition, strongly acidic solution, and presence of toxic
      metabolites. Therefore, exploring methods to improve the stress tolerance of host
      organisms could significantly improve the biotransformation process. With the
      help of synthetic biology, it is now becoming feasible to implement strategies to
      improve the stress-resistance of the existing hosts. This review summarizes
      synthetic biology efforts to enhance the efficiency of biotransformations by
      improving the robustness of microbes. Particular attention will be given to
      strategies at the cellular and the microbial community levels. 

PMID- 25368871
TI  - Simultaneous determination of iodide and creatinine in human urine by flow
      analysis with an on-line sample treatment column.
AB  - This work presents the first flow system for direct analysis of iodide and
      creatinine suitable for screening of human urine samples. The system had a mini
      column packed with strong anion exchange resin for on-line extraction of iodide.
      After injection of a sample on the column the unretained urine sample was
      analyzed for creatinine in one section of the flow system using the Jaffe's
      reaction with spectrometric detection at 520 nm. Iodide was eluted off with 1.42
      mL 5 M NaNO3. A 150 MUL fraction of the eluate was analyzed in another section of
      the same flow system for iodide using the kinetic-spectrometric Sandell-Kolthoff
      reaction. At the optimum condition, the sample throughput was 12 samples per h.
      The linear working range covered the normal levels of iodide and creatinine in
      human urine: 0-200 MUg I L(-1) and 50-1200 mg creatinine L(-1), respectively.
      Recoveries tested in 10 samples were 87-104% for iodide and 89-104% for
      creatinine. Bland-Altman plots (n = 50) showed that the scatter of the
      differences between values obtained by this method and those of reference
      methods, for both iodide and creatinine, was within mean +/- 2SD. 

PMID- 25368872
TI  - Binding studies and anion-selective electrodes with neutral isophthalamide-based
      receptors.
AB  - Two acyclic isophthalamide-based hosts have been synthesised and their anion
      binding properties have been evaluated by (1)H-NMR titrations. Different binding
      modes have been detected for the series of tested anions. The attachment of
      aminomethylpyrrole groups resulted in an improved binding selectivity.
      Additionally, the receptors have been incorporated as ionophores in plasticised
      polymeric membrane-based anion-selective electrodes. The potentiometric studies
      were in agreement with the NMR experiments and revealed a good sensing ability,
      considering the structural simplicity of the receptors and their interactions
      purely based on hydrogen bonding. These preliminary experiments have revealed an
      interesting selectivity towards highly hydrophilic anions such as fluoride and
      sulfate. Moreover, a particularly low detection limit (9 * 10(-7) M) has been
      determined for the fluoride anion. 

PMID- 25368870
TI  - What are my chances? Closing the gap in uncertainty monitoring between rhesus
      monkeys (Macaca mulatta) and capuchin monkeys (Cebus apella).
AB  - Previous studies have indicated that rhesus monkeys (Macaca mulatta) but not
      capuchin monkeys (Cebus apella) respond to difficult or ambiguous situations by
      choosing not to respond or by seeking more information. Here we assessed whether
      a task with very low chance accuracy could diminish this species difference,
      presumably indicating that capuchins-compared to macaques-are less risk averse as
      opposed to less sensitive to signals of uncertainty. Monkeys searched for the
      largest of 6 stimuli on a computer screen. Trial difficulty was varied, and
      monkeys could choose to opt out of any trial. All rhesus monkeys, including some
      with no prior use of the uncertainty response, selectively avoided the most
      difficult trials. The majority of capuchins sometimes made uncertainty responses,
      but at lower rates than rhesus monkeys. Nonetheless, the presence of some
      adaptive uncertainty responding suggests that capuchins also experience
      uncertainty and can respond to it, though with less proficiency than macaque
      monkeys.

PMID- 25368873
TI  - Separation of small metabolites and lipids in spectra from biopsies by diffusion
      weighted HR-MAS NMR: a feasibility study.
AB  - High Resolution Magic Angle Spinning (HR-MAS) NMR allows metabolic
      characterization of biopsies. HR-MAS spectra from tissues of most organs show
      strong lipid contributions that are overlapping metabolite regions, which hamper
      metabolite estimation. Metabolite quantification and analysis would benefit from
      a separation of lipids and small metabolites. Generally, a relaxation filter is
      used to reduce lipid contributions. However, the strong relaxation filter
      required to eliminate most of the lipids also reduces the signals for small
      metabolites. The aim of our study was therefore to investigate different
      diffusion editing techniques in order to employ diffusion differences for
      separating lipid and small metabolite contributions in the spectra from different
      organs for unbiased metabonomic analysis. Thus, 1D and 2D diffusion measurements
      were performed, and pure lipid spectra that were obtained at strong diffusion
      weighting (DW) were subtracted from those obtained at low DW, which include both
      small metabolites and lipids. This subtraction yielded almost lipid free small
      metabolite spectra from muscle tissue. Further improved separation was obtained
      by combining a 1D diffusion sequence with a T2-filter, with the subtraction
      method eliminating residual lipids from the spectra. Similar results obtained for
      biopsies of different organs suggest that this method is applicable in various
      tissue types. The elimination of lipids from HR-MAS spectra and the resulting
      less biased assessment of small metabolites have potential to remove ambiguities
      in the interpretation of metabonomic results. This is demonstrated in a
      reproducibility study on biopsies from human muscle. 

PMID- 25368874
TI  - Preparation of polyhedral oligomeric silsesquioxane based hybrid monoliths by
      thiol-ene click chemistry for capillary liquid chromatography.
AB  - A facile organic-silica hybrid monolith was prepared by a thiol-ene click
      reaction of polyhedral oligomeric silsesquioxane methacryl substituted (POSS-MA)
      with 1,4-bis(mercaptoacetoxy) butane (BMAB) using toluene and dodecanol as a
      porogenic system. The effects of the ratio of POSS-MA-BMAB and porogenic solvents
      and click reaction temperature on the morphology, permeability and column
      performance of the resulting POSS-BMAB hybrid monoliths were studied in detail. A
      uniform monolithic network with a high porosity was obtained. The POSS-BMAB
      hybrid monolith exhibited good permeability and high thermal and mechanical
      stability. A series of test compounds, including alkylbenzenes, polycyclic
      aromatic hydrocarbon, phenols and, anilines were used to evaluate the retention
      behaviors of the POSS-BMAB hybrid monolith in capillary liquid chromatography.
      The prepared POSS-BMAB hybrid monolith exhibited typical reversed-phase
      chromatographic behavior toward neutral solutes. The minimum plate height of this
      hybrid monolith was determined as 12.6 and 13.7 MUm for thiourea and benzene,
      respectively. These results demonstrate that thiol-ene click chemistry can
      provide a facile and robust approach for the preparation of a POSS-based hybrid
      monolith. 

PMID- 25368875
TI  - An adaptable stage perfusion incubator for the controlled cultivation of C2C12
      myoblasts.
AB  - Here we present a stage perfusion incubation system that allows for the
      cultivation of mammalian cells within PDMS microfluidic devices for long-term
      microscopic examination and analysis. The custom-built stage perfusion incubator
      is adaptable to any x-y microscope stage and is enabled for temperature, gas and
      humidity control as well as equipped with chip and tubing holder. The applied
      double-layered microfluidic chip allows the predetermined positioning and
      concentration of cells while the gas permeable PDMS material facilitates pH
      control via CO2 levels throughout the chip. We demonstrate the functionality of
      this system by culturing C2C12 murine myoblasts in buffer free medium within its
      confines for up to 26 hours. We moreover demonstrated the system's compatibility
      with various chip configurations, other cells lines (HEK-293 cells) and for
      longer-term culturing. The cost-efficient system are applicable for any type of
      PDMS-based cell culture system. Detailed technical drawings and specification to
      reproduce this perfusion incubation system is provided in the ESI. 

PMID- 25368877
TI  - Progress towards  poliomyelitis eradication:  Afghanistan and Pakistan,  January
      2013-August 2014.

PMID- 25368878
TI  - Polio-free certification of the WHO  South-East Asia Region, March 2014.

PMID- 25368876
TI  - Care of hepatitis C virus infection in France: modifications in three consecutive
      surveys between 1995 and 2010.
AB  - BACKGROUND & AIMS: To determine the characteristics of hepatitis C (HCV)-
      infected patients in 2010 and compare this survey with those reported in 1995 and
      2001. PATIENTS AND METHODS: Observational multicentre study conducted in 2010 in
      French internal medicine, infectious diseases and hepatology departments.
      RESULTS: A total of 1621 HCV infected patients (mean age 50.1 +/- 10.7 years; sex
      ratio M/F 1.8; genotype 1: 55.7%) were included. Of these, 910 (56.1%) were HIV
      HCV co-infected, 463 (40.4%) were asymptomatic and 184 (16.1%) had cirrhosis at
      inclusion in this study. Positive viraemia was found in 1,025 patients (65.5%) at
      inclusion in this study. A complete pretreatment evaluation including
      investigation for HCV RNA, genotype determination and liver fibrosis was
      performed in 96.5, 80.5 and 68.7% of the 1,621 patients respectively. Previous
      and ongoing HCV treatments were noted in 49.6% and 20.1% of patients
      respectively. A sustained virological response (SVR) was observed in 271/801
      (38.3%) patients, i.e. 44.1% and 30.7% in co-infected and mono-infected patients
      respectively. Cirrhosis was more frequent in the 2010 than in the 2001 and 1995
      surveys (16.1% vs. 10.4% and 7.4% respectively; P < 0.0001). A complete
      pretreatment evaluation was performed in 57.9% and 50.9% of patients in 2010 and
      2001 (P < 0.0001). Liver fibrosis evaluation was more frequent in 2010 than in
      the 2001 and 1995 surveys (68.7% vs. 62.7% and 28.7%, respectively, P < 0.0001).
      CONCLUSION: The care of HCV-infected patients has changed significantly in 'real
      life' through an improvement of pretreatment evaluation before the antiviral
      introduction and the increased use of antivirals. New HCV therapy combinations
      including protease inhibitors are warranted to increase the SVR rate.

PMID- 25368879
TI  - How does a gastroenterologist demonstrate value?

PMID- 25368881
TI  - Peptide-based inhibitors of Plk1 polo-box domain containing mono-anionic
      phosphothreonine esters and their pivaloyloxymethyl prodrugs.

PMID- 25368880
TI  - Reply by the authors of the original article.

PMID- 25368882
TI  - Molecular and biochemical modifications of liver glutamine synthetase  elicited
      by daytime restricted feeding.
AB  - BACKGROUND & AIMS: The circadian clock system in the liver plays important roles
      in regulating metabolism and energy homeostasis. Restricted feeding schedules
      (RFS) become an entraining stimulus that promotes adaptations that form part of
      an alternative circadian clock known as the food entrained oscillator (FEO). The
      aim of this study was to evaluate the daily variations of glutamine synthetase
      (GS) in liver under a daytime RFS. METHODS: Hepatic GS properties were analysed
      at 3-h intervals over a 24-h period in adult male Wistar rats maintained in a
      12:12 h light-dark cycle. RFS group: food access for 2-h in light phase, during 3
      weeks. AL group: feeding ad libitum. Fa group: acute fast (21 h). Fa-Re group:
      acute fast followed by refed 2 h.mRNA expression was measured by RT-qPCR, protein
      presence by Western-blot and immunohistochemistry, enzyme activity by a
      spectrophotometric assay, and glutamine by high pressure liquid chromatography.
      RESULTS AND CONCLUSIONS: Restricted feeding schedule induced circadian
      rhythmicity inmRNA levels of GS and the loss of the rhythmic pattern in
      mitochondrial GS activity. GS activity in liver homogenates displayed a robust
      rhythmic pattern in AL that was not modified by RFS. The presence of GS and its
      zonal distribution did not show rhythmic pattern in both groups. However, acute
      Fa and Fa-Re diminished GS protein and activity in liver homogenates. Hepatic
      glutamine concentrations showed a 24-h rhythmic pattern in both groups, in an
      antiphasic pattern. In conclusion, daytime RFS influences the liver GS system at
      different levels, that could be part of rheostatic adaptations associated to the
      FEO, and highlight the plasticity of this system.

PMID- 25368883
TI  - Sea urchin neural development and the metazoan paradigm of neurogenesis.
AB  - Summary:Urchin embryos continue to prove useful as a means of studying embryonic
      signaling and gene regulatory networks, which together control early development.
      Recent progress in understanding the molecular mechanisms underlying the
      patterning of ectoderm has renewed interest in urchin neurogenesis. We have
      employed an emerging model of neurogenesis that appears to be broadly shared by
      metazoans as a framework for this review. We use the model to provide context and
      summarize what is known about neurogenesis in urchin embryos. We review
      morphological features of the differentiation phase of neurogenesis and summarize
      current understanding of neural specification and regulation of proneural
      networks. Delta-Notch signaling is a common feature of metazoan neurogenesis that
      produces committed progenitors and it appears to be a critical phase of
      neurogenesis in urchin embryos. Descriptions of the differentiation phase of
      neurogenesis indicate a stereotypic sequence of neural differentiation and
      patterns of axonal growth. Features of neural differentiation are consistent with
      localized signals guiding growth cones with trophic, adhesive, and tropic cues.
      Urchins are a facile, postgenomic model with the potential of revealing many
      shared and derived features of deuterostome neurogenesis.

PMID- 25368884
TI  - In memoriam. Albert J. Stunkard.

PMID- 25368885
TI  - Rice.

PMID- 25368886
TI  - Rice by the numbers: A good grain.

PMID- 25368887
TI  - Agribiotechnology: Blue-sky rice.

PMID- 25368888
TI  - Biotechnology: Against the grain.

PMID- 25368889
TI  - Domestication: The birth of rice.

PMID- 25368890
TI  - Yield: The search for the rice of the future.

PMID- 25368891
TI  - Contamination: The toxic side of rice.

PMID- 25368892
TI  - Agriculture: The next frontier.

PMID- 25368893
TI  - Perspective: Time to unleash rice.

PMID- 25368894
TI  - How many procedures makes competency?

PMID- 25368896
TI  - All aboard for a new face in QI.

PMID- 25368895
TI  - Refocusing your readmissions reduction strategies.

PMID- 25368897
TI  - Stand-alone obs unit success.

PMID- 25368898
TI  - ECRI lauds health system for untethering patients.

PMID- 25368899
TI  - Hospitals can track, compare needlesticks.

PMID- 25368901
TI  - A crystal structure of an oligoproline PPII-helix, at last.
AB  - The first crystal structure of an oligoproline adopting an all-trans polyproline
      II (PPII) helix is presented. The high-resolution structure provides detailed
      insight into the dimensions and conformational properties of oligoprolines that
      are important for, e.g., their use as "molecular rulers" and "molecular
      scaffolds". The structure also showed that the amides interact with each other
      within a PPII helix and that water is not necessary for PPII helicity. 

PMID- 25368902
TI  - Erratum.
AB  - Platts, L. G., Webb, E., Zins, M., Goldberg, M., & Netuveli, G. (2014). Mid-life
      occupational grade and quality of life following retirement: a 16-year follow-up
      of the French GAZEL study. Aging & Mental Health. http://dx.doi.org/10.1080/
      13607863.2014.955458. When the above article was first published online, Loretta
      Platts' affiliation was erroneously listed as Department of Social Science,
      Institute of Gerontology, Health & Medicine. This has now been corrected in both
      the print and online versions to Institute of Gerontology, Department of Social
      Science, Health & Medicine. Taylor & Francis apologises for this error.

PMID- 25368900
TI  - A high throughput biochemical fluorometric method for measuring lipid
      peroxidation in HDL.
AB  - Current cell-based assays for determining the functional properties of high
      density lipoproteins (HDL) have limitations. We report here the development of a
      new, robust fluorometric cell-free biochemical assay that measures HDL lipid
      peroxidation (HDLox) based on the oxidation of the fluorochrome Amplex Red. HDLox
      correlated with previously validated cell-based (r = 0.47, p<0.001) and cell-free
      assays (r = 0.46, p<0.001). HDLox distinguished dysfunctional HDL in established
      animal models of atherosclerosis and Human Immunodeficiency Virus (HIV) patients.
      Using an immunoaffinity method for capturing HDL, we demonstrate the utility of
      this novel assay for measuring HDLox in a high throughput format. Furthermore,
      HDLox correlated significantly with measures of cardiovascular diseases including
      carotid intima media thickness (r = 0.35, p<0.01) and subendocardial viability
      ratio (r = -0.21, p = 0.05) and physiological parameters such as metabolic and
      anthropometric parameters (p<0.05). In conclusion, we report the development of a
      new fluorometric method that offers a reproducible and rapid means for
      determining HDL function/quality that is suitable for high throughput
      implementation.

PMID- 25368903
TI  - Capillarisin Exhibits Anticancer Effects by Inducing Apoptosis, Cell Cycle Arrest
      and Mitochondrial Membrane Potential Loss in Osteosarcoma Cancer Cells (HOS).
AB  - The aim of the present study was to assess the anticancer activity of
      capillarisin against human osteosarcoma (HOS) cancer cells in vitro. Cell
      viability after capillarisin drug treatment and evaluated by MTT assay. The
      extent of cell death induced by capillarisin was estimated by using lactate
      dehydrogenase (LDH) assay. The effect of capillarisin on cell cycle phase
      distribution and mitochondrial membrane potential (LambdaPsim) was demonstrated
      via flow cytometry using propidium iodide (PI) and rhodamine-123 (Rh-123) DNA
      binding fluorescent dyes respectively. Fluorescence microscopy was employed to
      examine the morphological changes in osteosarcoma cancer cells and presence of
      apoptotic bodies following capillarisin treatment. The results of this study
      revealed that capillarisin induced dose-dependent growth inhibition of these
      cancer cells after 12-h of incubation. Further, capillarisin induced significant
      release of LDH from these cell cultures and this LDH release was much more
      noticeable at higher concentrations of capillarisin. Hoechst 33258 staining
      revealed characteristic morphological features of apoptosis triggered by
      capillarisin treatment. Cell cycle analysis revealed that capillarisin induced
      dose-dependent G0/G1-phase cell cycle arrest. Capillarisin also trigerred a
      progressive and dose-dependent reduction in the mitochondrial membrane potential.
      In conclusion, capillarisin inhibits cancer cell growth of osteosarcoma cells by
      inducing apoptosis accompanied with G0/G1-phase cell cycle arrest and loss in
      mitochondrial membrane potential. 

PMID- 25368904
TI  - DPP-4 Inhibitor Teneligliptin Improves Insulin Resistance and Serum Lipid Profile
      in Japanese Patients with Type 2 Diabetes.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to improve the
      glycemic control and blood hemoglobin A1c (HbA1c) concentrations. However, there
      are few reports as yet suggesting that DPP-4 inhibitors may also improve insulin
      resistance and the serum lipid profile in the clinical setting. This study was
      aimed at investigating the effect of 14-week treatment with teneligliptin (20
      mg/day) on the homeostasis model assessment ratio (HOMA-R), an indicator of
      insulin resistance, and serum lipid profile in 9 patients with type 2 diabetes.
      The treatment produced a significant decrease of the blood glucose and HbA1c
      concentration (blood glucose: p=0.008; HbA1c: p=0.038), and also improved HOMA-R
      (p=0.039). Furthermore, the patients showed elevation of the serum HDL
      cholesterol level (p=0.032), and a tendency towards reduction of the serum
      triglyceride level. The results indicate that teneligliptin acts not only to
      improve the blood glucose control, but also to improve the insulin resistance and
      serum lipid profile in Japanese type 2 diabetes patients. 

PMID- 25368906
TI  - Elevated Expression of Nrf-2 and ABCG2 Involved in Multi-drug Resistance of Lung
      Cancer SP Cells.
AB  - BACKGROUND: Over expression of ATP-binding cassette (ABC) transporter protein
      (ABCG2) in side population cells plays a crucial role in the chemotherapeutic
      drug efflux. Constitutive expression of redox sensing transcritption factor Nrf2
      was shown to be involved in regulation of ABCG2 expression and chemoresistance.
      In the current study we made an attempt to characterize the lung adenocarcinoma
      SP cells. MATERIALS AND METHODS: We used FACs based Hoechst 33342 dye exclusion
      assay for purification of lung cancer SP cells. The sorted SP cells were
      subjected to drug resistance, sphere formation assays and gene expression
      analysis (Nrf2 and ABCG2). RESULTS: We have identified 2.9% of SP cells from lung
      cancer whose prevalence is significantly reduced to 0.3% upon treatment with
      verapamil. RT-PCR and western blot analysis revealed that Nrf2 and ABCG2 were
      highly expressed in lung cancer SP cells. Further, these SP cells are resistant
      to several chemotherapeutic drugs, self-renewal, and highly tumorigenic than non
      SP cells. CONCLUSIONS: Our data suggest that Nrf2-mediated ABCG2 over expression
      in lung adenocarcinoma SP cells might responsible for chemotherapy failure.
      Therefore, designing novel anticancer drugs that attenuates the Nrf2 and ABCG2
      expression, makes SP cells more sensitive to chemotherapy and thus prevent the
      tumor relapse.

PMID- 25368905
TI  - Evaluation of Protein Ubiquitylation in Heart Tissue of Rats Exposed to Diazinon
      (an Organophosphate Insecticide) and Crocin (an Active Saffron Ingredient): Role
      of HIF-1alpha.
AB  - INTRODUCTION: Organophosphate compounds, such as diazinon (DZN), are widely used
      in agriculture and can lead to formation of reactive oxygen species (ROS) in
      cardiovascular system. ROS are highly toxic since they can cause serious changes
      in proteins including ubiquitylation. Crocin (a carotenoid isolated from
      saffron), has protective effects against DZN cardiotoxicity. In this study level
      of total protein ubiquitylation as markers of oxidative stress and level of
      ubiquitin-HIF-1alpha and P53, known substrates of ubiquitylation, in rat hearts
      exposed to DZN and crocin were evaluated. METHODS: Rats were divided into 7
      groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, 50
      mg/kg/day, i. p.) plus DZN, vitamin E (200 IU/kg, i. p., 3 days a week) plus DZN
      and crocin (50 mg/kg/day, i. p.). Treatments were continued for 4 weeks. Total
      protein ubiquitylation, total HIF-1alpha and P53 were analyzed by western
      blotting. Total HIF-1alpha and P53 were purified by immunoprecipitation (IP) and
      ubiquitin- HIF-1alpha and P53 were analyzed by western blotting. RESULTS: Higher
      protein ubiquitylation levels were observed in DZN treated rats. Decrease in
      ubiquitin-HIF-1alpha was also shown, and leads to higher HIF-1alpha protein
      levels in DZN group. Crocin (50 mg/kg) and vit. E protected cells against DZN
      protein ubiquitylation. Significant differences were not observed between the
      ubiquitin - P53 and total P53 protein levels. CONCLUSION: Our results showed that
      ubiquitylation could be considered as a marker of oxidative stress in rats
      exposed to DZN. Increase in level of HIF-alpha may compensate adverse effect of
      DNZ in rat heart.

PMID- 25368907
TI  - Retention of implicit sequence learning in persons who stutter and persons with
      Parkinson's disease.
AB  - The authors investigated the retention of implicit sequence learning in 14
      persons with Parkinson's disease (PPD), 14 persons who stutter (PWS), and 14
      control participants. Participants completed a nonsense syllable serial reaction
      time task in a 120-min session. Participants named aloud 4 syllables in response
      to 4 visual stimuli. The syllables formed a repeating 8-item sequence not made
      known to participants. After 1 week, participants completed a 60-min retention
      session that included an explicit learning questionnaire and a sequence
      generation task. PPD showed retention of general learning equivalent to controls
      but PWS's reaction times were significantly slower on early trials of the
      retention test relative to other groups. Controls showed implicit learning during
      the initial session that was retained on the retention test. In contrast, PPD and
      PWS did not demonstrate significant implicit learning until the retention test
      suggesting intact, but delayed, learning and retention of implicit sequencing
      skills. All groups demonstrated similar limited explicit sequence knowledge.
      Performance differences between PWS and PPD relative to controls during the
      initial session and on early retention trials indicated possible dysfunction of
      the cortico-striato-thalamo-cortical loop. The etiological implications for
      stuttering, and clinical implications for both populations, of this dysfunction
      are discussed. 

PMID- 25368908
TI  - Immediate extubation after pediatric liver transplantation: a single-center
      experience.
AB  - The care of pediatric liver transplant recipients has traditionally included
      postoperative mechanical ventilation. In 2005, we started extubating children
      undergoing liver transplantation in the operating room according to standard
      criteria for extubation used for general surgery cases. We reviewed our single
      center experience to determine our rates of immediate extubation and practice
      since that time. The records of 84 children who underwent liver transplantation
      from 2005 to 2011 were retrospectively reviewed. The immediate extubation rate
      increased from 33% during 2005-2008 to 67% during 2009-2011. Immediate extubation
      did not result in an increased reintubation rate in comparison with delayed
      extubation in the intensive care unit (ICU). Patients undergoing immediate
      extubation had a trend toward a shorter mean ICU stay as well as a significantly
      decreased overall hospital length of stay. Our findings suggest that there is a
      learning curve for instituting immediate extubation in the operating room after
      liver transplantation and that the majority of pediatric liver recipients can
      safely undergo immediate extubation.

PMID- 25368909
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- 25368910
TI  - Submucous cleft palate: a systematic review of surgical management based on
      perceptual and instrumental analysis.
AB  - Objective : Submucous cleft palate (SMCP) is a congenital condition associated
      with abnormal development of the soft palate musculature. In a proportion of
      cases, this results in velopharyngeal insufficiency (VPI), the treatment for
      which includes pharyngeal flap surgery, pharyngoplasty, and palate
      reconstruction. The aim of this paper is to determine whether there is
      superiority of one or more types of surgical procedure over the others in
      improving speech in patients with VPI secondary to SMCP. Methodology : Nine
      databases, including MEDLINE and EMBASE, were searched between inception and
      January 2013 to identify articles published relating to the surgical management
      of SMCP. Only studies that reported outcome measures for postoperative speech
      were included in the systematic review. Results : Twenty-six studies analyzing
      the outcomes of surgery for VPI in patients with SMCP met the inclusion criteria.
      In these studies, speech outcomes were measured either in a binary fashion (i.e.,
      normal speech or evidence of VPI) or using scales of VPI severity. Of the 26
      studies, only two utilized blinded speech assessment, and 12 included both
      preoperative and postoperative speech assessment. Conclusions : The review found
      little evidence to support any specific surgical intervention. This is in large
      part due to the inclusion of mixed etiologies within study populations and the
      lack of unbiased validated preoperative and postoperative speech assessment.
      Further methodologically rigorous studies need to be conducted to provide a
      secure evidence base for the surgical management of SMCP. 

PMID- 25368912
TI  - Survivin-targeting Artificial MicroRNAs Mediated by Adenovirus Suppress Tumor
      Activity in Cancer Cells and Xenograft Models.
AB  - Survivin is highly expressed in most human tumors and fetal tissue, and absent in
      terminally differentiated cells. It promotes tumor cell proliferation by
      negatively regulating cell apoptosis and facilitating cell division. Survivin's
      selective expression pattern suggests that it might be a suitable target for
      cancer therapy, which would promote death of transformed but not normal cells.
      This was tested using artificial microRNAs (amiRNAs) targeting survivin. After
      screening, two effective amiRNAs, which knocked down survivin expression, were
      identified and cloned into a replication-defective adenoviral vector. Tumor cells
      infected with the recombinant vector downregulated expression of survivin and
      underwent apoptotic cell death. Further studies showed that apoptosis was
      associated with increases in caspase 3 and cleaved Poly (ADP-ribose) polymerase,
      and activation of the p53 signaling pathway. Furthermore, amiRNA treatment caused
      blockade of mitosis and cell cycle arrest at the G2/M phase. In vivo, survivin
      targeting amiRNAs expressed by adenoviral vectors effectively delayed growth of
      hepatocellular and cervical carcinomas in mouse xenograft models. These results
      indicate that silencing of survivin by amiRNA has potential for treatment of
      cancer. 

PMID- 25368914
TI  - Photolability of per-arylated butadienes: en route to dihydronaphthalenes.
AB  - Arylated butadienes were prepared employing transition-metal coupling techniques
      and characterized via UV/vis spectroscopy and X-ray crystal structure analysis.
      Identification of byproducts led to a photochemical route toward novel
      multiarylated dihydronaphthalenes. Arylbutadiene-dihydronaphthalene cyclization
      occurs in solution and in the solid state. Upon substitution of
      hexaphenylbutadiene, absorption is red-shifted and stability under ambient light
      is even more reduced. 

PMID- 25368913
TI  - Inhibition of monocyte adhesion to brain-derived endothelial cells by dual
      functional RNA chimeras.
AB  - Because adhesion of leukocytes to endothelial cells is the first step of vascular
      neuronal inflammation, inhibition of adhesion and recruitment of leukocytes to
      vascular endothelial cells will have a beneficial effect on neuroinflammatory
      diseases. In this study, we used the pRNA of bacteriophage phi29 DNA packaging
      motor to construct a novel RNA nanoparticle for specific targeting to transferrin
      receptor (TfR) on the murine brain-derived endothelial cells (bEND5) to deliver
      ICAM-1 siRNA. This RNA nanoparticle (FRS-NPs) contained a FB4 aptamer targeting
      to TfR and a siRNA moiety for silencing the intercellular adhesion molecule-1
      (ICAM-1). Our data indicated that this RNA nanoparticle was delivered into murine
      brain-derived endothelial cells. Furthermore, the siRNA was released from the FRS
      NPs in the cells and knocked down ICAM-1 expression in the TNF-alpha-stimulated
      cells and in the cells under oxygen-glucose deprivation/reoxygenation (OGD/R)
      condition. The functional end points of the study indicated that FRS-NPs
      significantly inhibited monocyte adhesion to the bEND5 cells induced by TNF-alpha
      and OGD/R. In conclusion, our approach using RNA nanotechnology for siRNA
      delivery could be potentially applied for inhibition of inflammation in ischemic
      stroke and other neuroinflammatory diseases, or diseases affecting endothelium of
      vasculature. 

PMID- 25368915
TI  - Overview of gene structure in C. elegans.
AB  - In the early stage of the C. elegans sequencing project, the ab initio gene
      prediction program Genefinder was used to find protein-coding genes.
      Subsequently, protein-coding genes structures have been actively curated by
      WormBase using evidence from all available data sources. Most coding loci were
      identified by the Genefinder program, but the process of gene curation results in
      a continual refinement of the details of gene structure, involving the correction
      and confirmation of intron splice sites, the addition of alternate splicing
      forms, the merging and splitting of incorrect predictions, and the creation and
      extension of 5' and 3' ends. The development of new technologies results in the
      availability of further data sources, and these are incorporated into the
      evidence used to support the curated structures. Non-coding genes are more
      difficult to curate using this methodology, and so the structures for most of
      these have been imported from the literature or from specialist databases of
      ncRNA data. This article describes the structure and curation of transcribed
      regions of genes. 

PMID- 25368916
TI  - High-resolution alpha-amylase assay combined with high-performance liquid
      chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy for
      expedited identification of alpha-amylase inhibitors: proof of concept and alpha
      amylase inhibitor in cinnamon.
AB  - Type 2 diabetes affects millions of people worldwide, and new improved drugs or
      functional foods containing selective alpha-amylase inhibitors are needed for
      improved management of blood glucose. In this article the development of a
      microplate-based high-resolution alpha-amylase inhibition assay with direct
      photometric measurement of alpha-amylase activity is described. The inhibition
      assay is based on porcine pancreatic alpha-amylase with 2-chloro-4-nitrophenyl
      alpha-D-maltotriose as substrate, which this gives a stable, sensitive, and cheap
      inhibition assay as requested for high-resolution purposes. In combination with
      HPLC-HRMS-SPE-NMR, this provides an analytical platform that allows simultaneous
      chemical and biological profiling of alpha-amylase inhibitors in plant extracts.
      Proof-of-concept with an artificial mixture of six compounds-of which three are
      known alpha-amylase inhibitors-showed that the high-resolution alpha-amylase
      inhibition profiles allowed detection of sub-microgram amounts of the alpha
      amylase inhibitors. Furthermore, the high-resolution alpha-amylase inhibition
      assay/HPLC-HRMS-SPE-NMR platform allowed identification of cinnamaldehyde as the
      alpha-amylase inhibitor in cinnamon (Cinnamomum verum Presl.).

PMID- 25368917
TI  - Lidocaine for Pain Control During IUD Placement.

PMID- 25368919
TI  - Primary care physicians' role in counseling about gun safety.

PMID- 25368921
TI  - Oral contraceptives are not an effective treatment for ovarian cysts.

PMID- 25368922
TI  - Screening for cancer: concepts and controversies.
AB  - Early detection of cancer is a core task in family medicine, and patients have
      come to expect screening tests, sometimes out of proportion to what evidence can
      justify. To understand the controversies surrounding screening and to provide
      sound advice to patients, family physicians should be familiar with the
      fundamental concepts of screening. Failure to account for the effects of lead
      time, length-time, and overdiagnosis biases can lead to overestimation of
      screening benefits. For this reason, the best method for evaluating the benefit
      of screening tests is a randomized controlled trial showing decreased disease
      specific or all-cause mortality. The number needed to screen can be used to
      measure the magnitude of benefit of screening tests. Accepted screening tests
      often require screening several hundred to more than 1,000 asymptomatic patients
      to prevent one death from the disease. The U.S. Preventive Services Task Force
      and American Academy of Family Physicians recommend screening for colorectal
      cancer in adults 50 to 75 years of age, and recommend against prostate-specific
      antigen testing to screen for prostate cancer. Annual low-dose computed
      tomography screening for lung cancer reduces mortality in persons 55 to 80 years
      of age with at least a 30-pack-year history who are otherwise healthy smokers or
      who have quit smoking within the past 15 years; however, it is associated with a
      high false-positive rate, uncertain harms from radiation exposure, and
      overdiagnosis. Therefore, it should be performed only in conjunction with smoking
      cessation interventions. 

PMID- 25368923
TI  - Acute pancreatitis.
AB  - Acute pancreatitis is most commonly caused by gallstones or chronic alcohol use,
      and accounts for more than 200,000 hospital admissions annually. Using the
      Atlanta criteria, acute pancreatitis is diagnosed when a patient presents with
      two of three findings, including abdominal pain suggestive of pancreatitis, serum
      amylase and/or lipase levels at least three times the normal level, and
      characteristic findings on imaging. It is important to distinguish mild from
      severe disease because severe pancreatitis has a mortality rate of up to 30%.
      Contrast-enhanced computed tomography is considered the diagnostic standard for
      radiologic evaluation of acute pancreatitis because of its success in predicting
      disease severity and prognosis. The BALI and computed tomography severity index
      scores also can aid in determining disease severity and predicting the likelihood
      of complications. Treatment begins with pain control, hydration, and bowel rest.
      In the first 48 to 72 hours of treatment, monitoring is required to prevent
      morbidity and mortality associated with worsening pancreatitis. When prolonged
      bowel rest is indicated, enteral nutrition is associated with lower rates of
      complications, including death, multiorgan failure, local complications, and
      systemic infections, than parenteral nutrition. In severe cases involving greater
      than 30% necrosis, antibiotic prophylaxis with imipenem/cilastatin decreases the
      risk of pancreatic infection. In gallstone-associated pancreatitis, early
      cholecystectomy and endoscopic retrograde cholangiopancreatography with
      sphincterotomy can decrease length of hospital stay and complication rates. A
      multidisciplinary approach to care is essential in cases involving pancreatic
      necrosis. 

PMID- 25368924
TI  - Multiple sclerosis: a primary care perspective.
AB  - Multiple sclerosis (MS) is the most common permanently disabling disorder of the
      central nervous system in young adults. Relapsing remitting MS is the most common
      type, and typical symptoms include sensory disturbances, Lhermitte sign, motor
      weakness, optic neuritis, impaired coordination, and fatigue. The course of
      disease is highly variable. The diagnosis is clinical and involves two neurologic
      deficits or objective attacks separated in time and space. Magnetic resonance
      imaging is helpful in confirming the diagnosis and excluding mimics. Symptom
      exacerbations affect 85% of patients with MS. Corticosteroids are the treatment
      of choice for patients with acute, significant symptoms. Disease-modifying agents
      should be initiated early in the treatment of MS to forestall disease and
      preserve function. Two immunomodulatory agents (interferon beta and glatiramer)
      and five immunosuppressive agents (fingolimod, teriflunomide, dimethyl fumarate,
      natalizumab, and mitoxantrone) are approved by the U.S. Food and Drug
      Administration for the treatment of MS, each with demonstrated effectiveness and
      unique adverse effect profiles. Symptom management constitutes a large part of
      care; neurogenic bladder and bowel, sexual dysfunction, pain, spasticity, and
      fatigue are best treated with a multidisciplinary approach to improve quality of
      life. 

PMID- 25368925
TI  - Mouth pain with red gums.

PMID- 25368926
TI  - Caring for unaccompanied minors from Central America.

PMID- 25368941
TI  - Associations of leisure-time sitting in cars with neighborhood walkability.
AB  - BACKGROUND: Too much sitting, including time spent sitting in cars, is associated
      with poor health outcomes. Identifying the built-environment attributes that may
      reduce vehicular sitting time can inform future initiatives linking the public
      health, urban design, and transportation sectors. METHODS: Data collected in 2003
      2004 from adult residents (n = 2521) of Adelaide, Australia were used. Logistic
      regression analyses examined associations of prolonged time spent sitting in cars
      during leisure time (30 min/day or more) with neighborhood walkability and its
      components (dwelling density; intersection density; land use mix; net retail area
      ratio). RESULTS: Lower overall walkability was significantly associated with a
      higher odds (OR = 1.43, 95% CI: 1.21-1.70) of spending prolonged time in cars.
      For analyses with walkability components, lower net retail area ratio, lower
      residential density, and lower intersection density were significantly associated
      with prolonged sitting in cars. CONCLUSION: This study found that residents of
      high walkable neighborhoods tended to spend less time sitting in cars. In
      particular, higher net retail area ratio, an indicator of tightly spaced
      commercial areas, was strongly associated with less time in cars. Policy and
      planning initiatives to reduce car use require further evidence, particularly on
      the influence of neighborhood retail areas.

PMID- 25368946
TI  - A Coordinated Comprehensive Professional Development Training's Effect on Summer
      Day Camp Staff Healthy Eating and Physical Activity Promoting Behaviors.
AB  - BACKGROUND: The YMCA of USA recently adopted Healthy Eating and Physical Activity
      (HEPA) Standards for their summer-day-camps (SDCs). Standards call for staff to
      exhibit HEPA promoting behaviors while eliminating HEPA discouraging behaviors.
      No studies have evaluated training programs to influence policy specified staff
      behaviors and related changes in child activity in SDCs. METHOD: Four YMCA SDCs
      serving approximately 800 children/week participated in this no control group
      pre/post pilot study. Professional development training founded in the 5 Ms
      (Mission, Model, Manage, Monitor, Maximize) and LET US Play principles (lines;
      elimination; team size; uninvolved staff/kids; and space, equipment, and rules)
      was delivered to staff. Outcomes were staff promotion behaviors and child
      activity assessed via systematic observation instruments. RESULTS: Twelve of 17
      HEPA staff behaviors changed in the appropriate direction from baseline to
      postassessment with 5 behaviors reaching statistically significant changes. The
      percentage of girls and boys observed in moderate-to-vigorous physical activity
      increased from 15.3% to 18.3% (P > .05) and 17.9% to 21.2%, whereas sedentary
      behavior decreased from 66.8% to 59.8% and 62.3% to 53.6%, respectively.
      CONCLUSION: Evidence suggests that the professional development training designed
      to assist SDCs to meet the HEPA Standards can lead to important changes in staff
      behaviors and children's physical activity.

PMID- 25368951
TI  - Daily physical activity behavior patterns of Hispanic adolescents in Puerto Rico.
AB  - BACKGROUND: There is limited evidence on physical activity patterns among
      Hispanic adolescents in Puerto Rico. This restricts opportunities to implement
      effective interventions and policies to increase physical activity in schools.
      The purpose of this study was to examine the physical activity behaviors of
      adolescents attending middle and high schools in Puerto Rico based on a
      compendium of moderate to vigorous physical activities including walking, jogging
      or running, bicycling, sports and more. A secondary purpose was to examine group
      differences as a function of gender and school level. METHOD: A cross-sectional
      survey research design was used. Students (N = 637) attending public middle and
      high schools completed a Visual 7-Day Physical Activity Recall survey. Both
      descriptive and inferential analyses were conducted to describe the sample and to
      determine group differences. RESULTS: Puerto Rican adolescents' levels of
      physical activity decreased throughout the week. Only a small proportion of them
      reached at least 60 minutes everyday of the week. Differences were found between
      middle and high school students' daily and weekly participation in physical
      activities. CONCLUSIONS: Most adolescents do not engage in sufficient physical
      activity. IMPLICATIONS: IMPLICATIONS of the results are discussed and
      recommendations are articulated for policy makers, educators, and other
      professionals.

PMID- 25368959
TI  - Treatment of aging vocal folds: novel approaches.
AB  - PURPOSE OF REVIEW: This article aims to review previous research reports and to
      summarize current strategies for the treatment of the aging vocal fold using
      regenerative medicine and tissue engineering, with a particular focus on growth
      factor therapy. RECENT FINDINGS: Previous studies have elucidated age-related
      histological and gene expression changes in key extracellular matrix components,
      such as collagen and hyaluronan, in the lamina propria of the aging vocal fold.
      On the basis of these findings, our research group has focused on growth factor
      therapy to restore extracellular matrix distribution in the aging vocal fold to a
      younger state. Results from recent studies with basic fibroblast growth factor
      and hepatocyte growth factor provided preliminary evidence of the regenerative
      effects of growth factor therapy on treatment of the aging vocal fold. In
      addition, a clinical trial using basic fibroblast growth factor revealed
      improvements of maximum phonation time, mean flow rate, and acoustic parameters
      in atrophied vocal folds. These positive findings suggest that the administration
      of basic fibroblast growth factor may become a useful tool for the treatment of
      the aging vocal fold. SUMMARY: Regenerative medicine and tissue engineering are
      innovative strategies for the treatment of aging vocal folds, and recent reports
      have also confirmed the therapeutic potential of growth factor therapy for the
      treatment of the aging vocal fold. More recently, the clinical application of
      basic fibroblast growth factor was reported with encouraging outcomes. Continued
      basic research and clinical investigations will be required to develop strategies
      to overcome age-related voice disorders.

PMID- 25368957
TI  - On-treatment prediction of sustained response to peginterferon alfa-2a for HBeAg
      negative chronic hepatitis B patients.
AB  - BACKGROUND & AIMS: We assessed predictors of response in HBeAg-negative chronic
      hepatitis B patients treated with peginterferon alfa-2a in routine clinical
      practice. METHODS: Ninety-five HBeAg-negative patients received peginterferonalfa
      2a for 48 weeks and were followed-up for 48 weeks post-treatment. Serum HBsAg and
      HBV DNA levels were monitored during and after therapy with valid commercial
      assays. Sustained response (SR) was defined as HBV DNA <2000 IU/ml at study week
      96. RESULTS: Twenty-two patients (23%) achieved SR and nine (9.5%) lost HBsAg.
      HBsAg decline was more profound in patients with SR. HBsAg decline >=10% from
      baseline to week 24 was significantly associated with SR [81% (17/21) vs 37%
      (21/57); Odds ratio: 7.286 (2.162-24.552), P = 0.001]. The PARC rule (no decrease
      in HBsAg and <2 log drop in HBV DNA at week 12) was evaluated in a subset of 47
      patients. Among eight patients who fulfilled the PARC rule, none achieved SR. Of
      the 39 patients who did not fulfil the PARC rule, 24 (62%) had HBsAg decline of
      >=10% at week 24 (12 achieved SR) and 15 (38%) had HBsAg decline of <10% (1
      achieved SR; negative predictive value: 93%). CONCLUSIONS: In HBeAg-negative
      chronic hepatitis B patients treated with peginterferon alfa-2a, HBsAg decline
      >10% at 24 weeks is significantly associated with SR. The combination of the PARC
      rule and week 24 decline in HBsAg can identify almost two-thirds of patients who
      are unlikely to achieve SR. Clinicaltrials.gov identifier: NCT01283074.

PMID- 25368960
TI  - Biphenyl-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-methylamide (CA224), a
      nonplanar analogue of fascaplysin, inhibits Cdk4 and tubulin polymerization:
      evaluation of in vitro and in vivo anticancer activity.
AB  - Biphenyl-4-carboxylic acid-[2-(1H-indol-3-yl)-ethyl]-methylamide 1 (CA224) is a
      nonplanar analogue of fascaplysin (2) that specifically inhibits Cdk4-cyclin D1
      in vitro. Compound 1 blocks the growth of cancer cells at G0/G1 phase of the cell
      cycle. It also blocks the cell cycle at G2/M phase, which is explained by the
      fact that it inhibits tubulin polymerization. Additionally, it acts as an
      enhancer of depolymerization for taxol-stabilized tubulin. Western blot analyses
      of p53-positive cancer cells treated with compound 1 indicated upregulation of
      p53, p21, and p27 proteins together with downregulation of cyclin B1 and Cdk1.
      Compound 1 selectively induces apoptosis of SV40 large T-antigen transformed
      cells and significantly reduces colony formation efficiency, in a dose-dependent
      manner, of lung cancer cells. It is efficacious at 1/10th of the MTD against
      human tumors derived from HCT-116 and NCI-H460 cells in SCID mouse models. The
      promising efficacy of compound 1 in human xenograft models as well as its
      excellent therapeutic window indicates its potential for clinical development. 

PMID- 25368961
TI  - PRESAGE 3D dosimetry accurately measures Gamma Knife output factors.
AB  - Small-field output factor measurements are traditionally very difficult because
      of steep dose gradients, loss of lateral electronic equilibrium, and dose volume
      averaging in finitely sized detectors. Three-dimensional (3D) dosimetry is ideal
      for measuring small output factors and avoids many of these potential challenges
      of point and 2D detectors. PRESAGE 3D polymer dosimeters were used to measure the
      output factors for the 4 mm and 8 mm collimators of the Leksell Perfexion Gamma
      Knife radiosurgery treatment system. Discrepancies between the planned and
      measured distance between shot centers were also investigated. A Gamma Knife head
      frame was mounted onto an anthropomorphic head phantom. Special inserts were
      machined to hold 60 mm diameter, 70 mm tall cylindrical PRESAGE dosimeters. The
      phantom was irradiated with one 16 mm shot and either one 4 mm or one 8 mm shot,
      to a prescribed dose of either 3 Gy or 4 Gy to the 50% isodose line. The two
      shots were spaced between 30 mm and 60 mm apart and aligned along the central
      axis of the cylinder. The Presage dosimeters were measured using the DMOS-RPC
      optical CT scanning system. Five independent 4 mm output factor measurements fell
      within 2% of the manufacturer's Monte Carlo simulation-derived nominal value, as
      did two independent 8 mm output factor measurements. The measured distances
      between shot centers varied by +/- 0.8 mm with respect to the planned shot
      displacements. On the basis of these results, we conclude that PRESAGE dosimetry
      is excellently suited to quantify the difficult-to-measure Gamma Knife output
      factors.

PMID- 25368962
TI  - Measurement of extreme hyperfine fields in two-coordinate high-spin Fe2+
      complexes by Mossbauer spectroscopy: essentially free-ion magnetism in the solid
      state.
AB  - Mossbauer studies of three two-coordinate linear high-spin Fe(2+) compounds,
      namely, Fe{N(SiMe3)(Dipp)}2 (1) (Dipp = C6H3-2,6-(i)Pr2), Fe(OAr')2 (2) [Ar' =
      C6H3-2,6-(C6H3-2,6-(i)Pr2)2], and Fe{C(SiMe3)3}2 (3), are presented. The
      complexes were characterized by zero- and applied-field Mossbauer spectroscopy (1
      3), as well as zero- and applied-field heat-capacity measurements (3). As 1-3 are
      rigorously linear, the distortion(s) that might normally be expected in view of
      the Jahn-Teller theorem need not necessarily apply. We find that the resulting
      very large unquenched orbital angular momentum leads to what we believe to be the
      largest observed internal magnetic field to date in a high-spin iron(II)
      compound, specifically +162 T in 1. The latter field is strongly polarized along
      the directions of the external field for both longitudinal and transverse field
      applications. For the longitudinal case, the applied field increases the overall
      hyperfine splitting consistent with a dominant orbital contribution to the
      effective internal field. By contrast, 2 has an internal field that is not as
      strongly polarized along a longitudinally applied field and is smaller in
      magnitude at ca. 116 T. Complex 3 behaves similarly to complex 1. They are
      sufficiently self-dilute (e.g., Fe...Fe distances of ca. 9-10 A) to exhibit
      varying degrees of slow paramagnetic relaxation in zero field for the neat solid
      form. In the absence of EPR signals for 1-3, we show that heat-capacity
      measurements for one of the complexes (3) establish a geff value near 12, in
      agreement with the principal component of the ligand electric field gradient
      being coincident with the z axis. 

PMID- 25368963
TI  - Pyrrolidinium-based ionic liquids doped with lithium salts: how does Li(+)
      coordination affect its diffusivity?
AB  - We present the characterization of LiX-doped room-temperature ionic liquids (ILs)
      based on the N-butyl-N-methyl pyrrolidinium (PYR14) cation with two fluorinated
      anions: (trifluoromethanesulfonyl)-(nonafluorobutanesulfonyl)imide (X?IM14) and
      bis(pentafluoroethanesulfonyl)imide (X?BETI). The new data are also compared with
      previous results on PYR14TFSI (bis(trifluoromethanesulfonyl)imide). Their local
      organization has been investigated via NMR nuclear Overhauser effect (NOE)
      experiments for {(1)H-(19)F} and {(1)H-(7)Li} that give us details on PYR14(+)/X(
      ) and PYR14(+)/Li(+) contacts. We confirm the presence of [Li(X)2](-) coordinated
      species in all systems. The long-range, intermolecular NOEs have been detected
      and provide information on the ions' organization beyond the first solvation
      sphere. The ionic conductivity, viscosity and self-diffusion coefficients of the
      ionic mixtures have also been measured. The activation energies for the diffusion
      of the individual ions and for the fluidity are compared with those for the pure
      ILs. Finally, density functional calculations on [Li(BETI)2](-), [Li(IM14)2](-),
      and [Li(TFSI)2](-) complexes demonstrate that the minimum energy structures for
      all systems correspond to a tetrahedral coordination of the Li-ion by four oxygen
      atoms of the anions. Assuming very simple key steps for the Li(+) diffusion
      process (i.e., the concerted breaking and formation of Li-O bonds or the
      rearrangement around a tetrahedrally coordinated Li(+)), we calculate activation
      barriers that agree well with the experimental results (approximately 46 kJ/mol,
      in all systems). 

PMID- 25368965
TI  - Read-across approaches--misconceptions, promises and challenges ahead.
AB  - Read-across is a data gap filling technique used within category and analogue
      approaches. It has been utilized as an alternative approach to address
      information requirements under various past and present regulatory programs such
      as the OECD High Production Volume Programme as well as the EU's Registration,
      Evaluation, Authorisation and restriction of CHemicals (REACH) regulation.
      Although read-across raises a number of expectations, many misconceptions still
      remain around what it truly represents; how to address its associated
      justification in a robust and scientifically credible manner; what
      challenges/issues exist in terms of its application and acceptance; and what
      future efforts are needed to resolve them. In terms of future enhancements, read
      across is likely to embrace more biologically-orientated approaches consistent
      with the Toxicity in the 21st Century vision (Tox-21c). This Food for Thought
      article, which is notably not a consensus report, aims to discuss a number of
      these aspects and, in doing so, to raise awareness of the ongoing efforts and
      activities to enhance read-across. It also intends to set the agenda for a CAAT
      read-across initiative in 2014-2015 to facilitate the proper use of this
      technique.

PMID- 25368964
TI  - Regulator of G-protein signaling 2 repression exacerbates airway hyper
      responsiveness and remodeling in asthma.
AB  - G protein-coupled receptors (GPCRs) are important regulators of cell functions in
      asthma. We recently reported that regulator of G-protein signaling (RGS) 2, a
      selective modulator of Gq-coupled GPCRs, is a key regulator of airway hyper
      responsiveness (AHR), the pathophysiologic hallmark of asthma. Because RGS2
      protein levels in airway cells were significantly lower in patients with asthma
      compared with patients without asthma, we further investigated the potential
      pathological importance of RGS2 repression in asthma. The human RGS2 gene maps to
      chromosome 1q31. We first screened patients with asthma for RGS2 gene promoter
      single-nucleotide polymorphisms (SNPs) and found significant differences in the
      distribution of two RGS2 SNPs (A638G, rs2746071 and C395G, rs2746072) between
      patients with asthma and nonasthmatic subjects. These two SNPs are always
      associated with each other and have the same higher prevalence in patients with
      asthma (65%) as compared with nonasthmatic subjects (35%). Point mutations
      corresponding to these SNPs decrease RGS2 promoter activity by 44%. The
      importance of RGS2 down-regulation was then determined in an acute IL-13 mouse
      model of asthma. Intranasal administration of IL-13 in mice also decreased RGS2
      expression in lungs by ~50% and caused AHR. Although naive RGS2 knockout (KO)
      mice exhibit spontaneous AHR, acute IL-13 exposure further increased AHR in RGS2
      KO mice. Loss of RGS2 also significantly enhanced IL-13-induced mouse airway
      remodeling, including peribronchial smooth muscle thickening and fibrosis,
      without effects on goblet cell hyperplasia or airway inflammation in mice. Thus,
      genetic variations and increased inflammatory cytokines can lead to RGS2
      repression, which exacerbates AHR and airway remodeling in asthma. 

PMID- 25368969
TI  - ACS report highlights growing population of cancer survivors: increase will
      require improvements in screening, long-term follow-up.

PMID- 25368968
TI  - Phase II study of methotrexate, vincristine, pegylated-asparaginase, and
      dexamethasone (MOpAD) in patients with relapsed/refractory acute lymphoblastic
      leukemia.
AB  - Newer approaches are needed for the treatment of relapsed and refractory acute
      lymphoblastic leukemia (ALL). Asparaginase-based regimens are active in the
      treatment of pediatric ALL and may be important in salvage therapy for adult
      patients. We conducted a pilot trial combining methotrexate, vincristine,
      PEGylated-asparaginase, and dexamethasone (MOpAD) in adults with relapsed or
      refractory ALL. We added tyrosine kinase inhibitors in patients with Philadelphia
      chromosome positive (Ph+) ALL and rituximab in patients with CD20 positive B-cell
      ALL. Among 37 patients treated (median age 42 years; median 2 prior therapies),
      the complete remission (CR) rate was 28% and an overall response rate (ORR) was
      39%. The median CR duration was 4.3 months. Patients with Ph+ ALL had CR and ORR
      of 50% and 67%, respectively and the CR and ORR in patients with T-cell leukemia
      were 45% and 56%, respectively. The median survival in patients with CR/CRp was
      10.4 versus 3.4 months in nonresponders (P = 0.02). The most common grade 3 or 4
      nonhematologic toxicities were elevations in bilirubin and transaminases, nausea,
      peripheral neuropathy, and hyperglycemia, which were managed with supportive
      care, dose adjustments, and interruptions.

PMID- 25368970
TI  - Epigenetic test could eliminate repeat biopsies for prostate cancer.

PMID- 25368971
TI  - Researchers find link between high cholesterol and breast cancer.

PMID- 25368972
TI  - Lanthanide-doped CaS and SrS luminescent nanocrystals: a single-source precursor
      approach for doping.
AB  - The incorporation of dopants with optical or magnetic functionalities into
      colloidal nanocrystals (NCs) has been a longstanding challenge for nanomaterial
      research. A deeper understanding of the doping kinetics will aid a better control
      of the doping process. In particular, alkaline-earth sulfides are an important
      class of host materials for a range of luminescent dopants, including transition
      metal and lanthanide ions. Their nanocrystalline analogues have many potential
      applications. However, the lack of synthetic methodologies hampers their
      development. Here we introduce a single-source precursor approach that
      successfully leads to Ce(3+)- and Eu(2+)-doped CaS and SrS luminescent NCs with
      diameters of ~10 nm and with luminescent properties similar to those of the bulk
      analogues. The characteristic absorption and luminescence of Ce(3+) and Eu(2+)
      depend on the local coordination and are applied to probe dopant ion
      internalization. We demonstrate that controlling the reactivity of the precursors
      is crucial for achieving effective doping. By designing the chemical structure of
      the dopant precursor to vary the reactivity relative to that of the host
      precursor, the doping efficiency can be controlled. In addition, we have applied
      a growth doping strategy to further improve internalization of the dopants.
      Finally, we demonstrate nucleation doping as an alternative method to achieve
      lanthanide NC doping for dopant and host precursors with strongly different
      reactivities. The single-source precursor approaches proposed here allow for a
      flexible design of synthesis strategies and have the potential to be widely
      applicable to the doping of colloidal chalcogenide NCs with transition-metal and
      lanthanide dopant ions. 

PMID- 25368973
TI  - Structural details of light activation of the LOV2-based photoswitch PA-Rac1.
AB  - Optical control of cellular processes is an emerging approach for studying
      biological systems, affording control with high spatial and temporal resolution.
      Specifically designed artificial photoswitches add an interesting extension to
      naturally occurring light-regulated functionalities. However, despite a great
      deal of structural information, the generation of new tools cannot be based fully
      on rational design yet; in many cases design is limited by our understanding of
      molecular details of light activation and signal transduction. Our biochemical
      and biophysical studies on the established optogenetic tool PA-Rac1, the
      photoactivatable small GTPase Rac1, reveal how unexpected details of the sensor
      effector interface, such as metal coordination, significantly affect functionally
      important structural elements of this photoswitch. Together with solution
      scattering experiments, our results favor differences in the population of pre
      existing conformations as the underlying allosteric activation mechanism of PA
      Rac1, rather than the assumed release of the Rac1 domain from the caging
      photoreceptor domain. These results have implications for the design of new
      optogenetic tools and highlight the importance of including molecular details of
      the sensor-effector interface, which is however difficult to assess during the
      initial design of novel artificial photoswitches. 

PMID- 25368975
TI  - Development of linear free energy relationships for aqueous phase radical
      involved chemical reactions.
AB  - Aqueous phase advanced oxidation processes (AOPs) produce hydroxyl radicals (HO*)
      which can completely oxidize electron rich organic compounds. The proper design
      and operation of AOPs require that we predict the formation and fate of the
      byproducts and their associated toxicity. Accordingly, there is a need to develop
      a first-principles kinetic model that can predict the dominant reaction pathways
      that potentially produce toxic byproducts. We have published some of our efforts
      on predicting the elementary reaction pathways and the HO* rate constants. Here
      we develop linear free energy relationships (LFERs) that predict the rate
      constants for aqueous phase radical reactions. The LFERs relate experimentally
      obtained kinetic rate constants to quantum mechanically calculated aqueous phase
      free energies of activation. The LFERs have been applied to 101 reactions,
      including (1) HO* addition to 15 aromatic compounds; (2) addition of molecular
      oxygen to 65 carbon-centered aliphatic and cyclohexadienyl radicals; (3)
      disproportionation of 10 peroxyl radicals, and (4) unimolecular decay of nine
      peroxyl radicals. The LFERs correlations predict the rate constants within a
      factor of 2 from the experimental values for HO* reactions and molecular oxygen
      addition, and a factor of 5 for peroxyl radical reactions. The LFERs and the
      elementary reaction pathways will enable us to predict the formation and initial
      fate of the byproducts in AOPs. Furthermore, our methodology can be applied to
      other environmental processes in which aqueous phase radical-involved reactions
      occur.

PMID- 25368974
TI  - Global metabolomic and isobaric tagging capillary liquid chromatography-tandem
      mass spectrometry approaches for uncovering pathway dysfunction in diabetic mouse
      aorta.
AB  - Despite the prevalence of diabetes and the global health risks it poses, the
      biochemical pathogenesis of diabetic complications remains poorly understood with
      few effective therapies. This study employs capillary liquid chromatography
      (capLC) and tandem mass spectrometry (MS/MS) in conjunction with both global
      metabolomics and isobaric tags specific to amines and carbonyls to probe aortic
      metabolic content in diabetic mice with hyperglycemia, hyperlipidemia,
      hypertension, and stenotic vascular damage. Using these combined techniques,
      metabolites well-characterized in diabetes as well as novel pathways were
      investigated. A total of 53,986 features were detected, 719 compounds were
      identified as having significant fold changes (thresholds >= 2 or <= 0.5), and 48
      metabolic pathways were found to be altered with at least 2 metabolite hits in
      diabetic samples. Pathways related to carbonyl stress, carbohydrate metabolism,
      and amino acid metabolism showed the greatest number of metabolite changes. Three
      novel pathways with previously limited or undescribed roles in diabetic
      complications--vitamin B6, propanoate, and butanoate metabolism--were also shown
      to be altered in multiple points along the pathway. These discoveries support the
      theory that diabetic vascular complications arise from the interplay of a myriad
      of metabolic pathways in conjunction with oxidative and carbonyl stress, which
      may provide not only new and much needed biomarkers but also insights into novel
      therapeutic targets.

PMID- 25368976
TI  - Trabecular bone score as an indicator for skeletal deterioration in diabetes.
AB  - CONTEXT: Trabecular bone score (TBS) is a novel texture index that evaluates the
      pixel gray-level variations in lumbar spine dual-energy X-ray absorptiometry
      images and is related to bone microarchitecture independent of bone mineral
      density (BMD). OBJECTIVE: We investigated lumbar spine TBS as an indicator for
      skeletal deterioration in diabetes. DESIGN AND SETTING: Cross-sectional data were
      collected from subjects participating in an ongoing prospective, community-based,
      cohort study from 2009 to 2010. PARTICIPANTS: We included 1229 men and 1529
      postmenopausal women older than 50 years in the Ansung cohort. OUTCOME MEASURES:
      Biochemical parameters, lumbar spine TBS, and BMD from dual-energy X-ray
      absorptiometry images were measured. RESULTS: Lumbar spine TBS was lower in men
      with diabetes than in nondiabetic men (1.287 +/- 0.005 vs 1.316 +/- 0.003, P <
      .001), whereas lumbar spine BMD was higher in men with diabetes (1.135 +/- 0.010
      vs 1.088 +/- 0.006 g/cm(2)). Lumbar spine TBS was lower in women with diabetes
      than in nondiabetic women only in an unadjusted model (1.333 +/- 0.004 vs 1.353
      +/- 0.003). However, women younger than 65 years (n = 707) with diabetes had a
      lower TBS than those without diabetes, even after adjusted for covariates (P <
      .001). Diabetes was not associated with BMD at femur sites in both genders. TBS
      was negatively correlated with glycated hemoglobin, fasting plasma glucose,
      fasting insulin, and homeostasis model assessment for insulin resistance but not
      with homeostasis model assessment for beta-cell function in both genders.
      CONCLUSIONS: The inverse association between lumbar spine TBS and insulin
      resistance may make it an indicator for determining skeletal deterioration in
      diabetic patients who have high BMD.

PMID- 25368977
TI  - The association between insulin resistance and vascularization of thyroid
      nodules.
AB  - CONTEXT: Insulin resistance (IR) is an important factor for the growth and
      progression of thyroid nodules, which might be associated with the distribution,
      construction, and density of nodular vascularization. OBJECTIVE: The objective of
      the study was to explore the association between IR and the vascularization of
      thyroid nodules. DESIGN AND SETTING: A cross-sectional, population-based study
      was conducted in Nanjing, China, from June to November 2011. PARTICIPANTS: Among
      10 050 participants aged 40-79 years, 2886 thyroid nodule cases were detected and
      2532 cases met eligibility criteria for enrollment in the study. MAIN OUTCOME
      MEASURES: Power Doppler was performed to measure the flow patterns, resistive
      index (RI), and vascular index (VI) of thyroid nodular vascularization. Fasting
      insulin, fasting glucose, 2-hour oral glucose tolerance test, glycosylated
      hemoglobin (HbA1c), homeostasis model assessment of IR (HOMA-IR), and body mass
      index were also tested. RESULTS: HOMA-IR (R = 0.35, P < .001) and HbA1c (R =
      0.19, P < .001) were positively correlated with thyroid nodular flow patterns,
      and the positive correlations were more significant in participants with large
      nodules (volume >= 0.2 mL). Additionally, in participants with large nodules,
      HOMA-IR and HbA1c were positively correlated with RI (HOMA-IR: beta = .42, SE =
      .03, R = 0.43, P < .001; HbA1c: beta = .22, SE = .04, R = 0.23, P < .001) and VI
      (HOMA-IR: beta = .49, SE = 0.05, R = 0.53, P < .001; HbA1c: beta = .34, SE =
      0.11, R = 0.37, P < .001). CONCLUSIONS: IR and hyperglycemia were positively
      correlated with the flow patterns, RI, and VI of thyroid nodules, especially in
      large nodules. The findings suggest a pivotal role of IR in the distribution,
      construction, and density of thyroid nodular vascularization, which might
      contribute to the growth and the progression of thyroid nodules.

PMID- 25368978
TI  - Dietary protein intake affects amino acid and acylcarnitine metabolism in infants
      aged 6 months.
AB  - CONTEXT: The protective effect of breast-feeding against later obesity may be
      explained by the lower protein content compared with formula milk. However, the
      metabolic mechanisms remain unknown. OBJECTIVE: We studied the metabolic response
      to a higher or lower protein supply in infancy. DESIGN AND SETTING: The Childhood
      Obesity Project study is a double-blind, randomized, multicenter intervention
      trial. Infants were randomized to receive a higher (HP) or lower protein (LP)
      content infant formula or were breast-fed. PATIENTS AND INTERVENTIONS: Plasma
      samples of 691 infants who received formula milk with different protein content
      (HP, 2.05 g per 100 mL; LP, 1.25 g per 100 mL) or were breast-fed were collected.
      MAIN OUTCOME MEASURES: Changes in plasma amino acid and acylcarnitine
      concentrations of 6-month-old infants according to different dietary protein
      supply were determined by liquid chromatography coupled to tandem mass
      spectrometry. RESULTS: Twenty-nine metabolites differed significantly between the
      formula groups. Branched-chain amino acids (BCAAs) were the most discriminant
      metabolites. Their degradation products, the short-chain acylcarnitines C3, C4,
      and C5, were also significantly elevated in the HP group. A breakpoint analysis
      confirmed that with increasing BCAAs, the ratio between acylcarnitines and BCAAs
      decreases. Long-chain acylcarnitines were decreased in HP infants. CONCLUSIONS:
      BCAAs seem to play a pivotal role in the effect of a high-protein diet on beta
      oxidation and fat storage. We provide new evidence for a possible saturation of
      the BCAA degradation pathway that may represent the mechanism by which high
      protein intake affects the metabolic regulation. Moreover, it appears to inhibit
      the initial step of the beta-oxidation, thus leading to high early weight gain
      and body fat deposition.

PMID- 25368980
TI  - Role of nanocrystalline silver dressings in the management of toxic epidermal
      necrolysis (TEN) and TEN/Stevens-Johnson syndrome overlap.
AB  - Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are severe
      mucocutaneous eruptions. There is currently no defined optimal approach to wound
      care. The objective of this study was to evaluate silver dressings in the wound
      care management of TEN and SJS/TEN syndrome overlap with a retrospective case
      review of nine patients with TEN and SJS/TEN overlap presenting to our
      institution. Nanocrystalline silver dressings appear to be useful in the rapid
      commencement of healing in these patients. TEN and SJS/TEN overlap are rare
      conditions. This contributed to a relatively small number of cases included in
      the study. The ease of application, antimicrobial properties and low frequency of
      change make nanocrystalline silver dressings ideal in TEN/SJS. 

PMID- 25368979
TI  - Circadian rhythm of circulating levels of the endocannabinoid 2
      arachidonoylglycerol.
AB  - CONTEXT: The endocannabinoid (eCB) system is involved in the regulation of food
      intake and of peripheral metabolism. Although the cross talk between energy
      metabolism and the circadian system is well documented, little is known about a
      potential circadian modulation of human eCB activity. OBJECTIVE: The objective of
      the study was to define the 24-hour profile of circulating levels of the most
      abundant endogenous ligand of the CB1 receptor, 2-arachidonoylglycerol (2-AG), in
      healthy young nonobese adults studied under controlled bedtime, dietary, and
      activity conditions. METHODS: Fourteen subjects participated in this 4-day
      laboratory study with fixed light-dark cycles, standardized meals, and bedtimes.
      Sleep was recorded each night. On the third day, blood sampling at 15- to 30
      minute intervals began at 9:30 pm and continued for 24 hours. Cortisol, leptin,
      and ghrelin were assayed on all samples, whereas the levels of 2-AG and its
      structural analog, 2-oleoylglycerol (2-OG), were measured at 60-minute intervals.
      RESULTS: All participants exhibited a large circadian variation of 2-AG serum
      concentrations with a nadir around midsleep, coincident with the middle of the
      overnight fast. Levels of 2-AG increased continually across the morning, peaking
      in the early to midafternoon. Peak values represented, on average, a nearly 3
      fold increase above nocturnal nadir levels. Concentrations of 2-OG followed a
      similar pattern, although with a shorter morning increase and lower amplitude.
      CONCLUSIONS: The findings demonstrate that activity of the eCB system is
      profoundly modulated by circadian rhythmicity and suggest that its impact on the
      regulation of food intake is suppressed during sleep and is maximal during early
      to midafternoon.

PMID- 25368982
TI  - Can alternative sugar sources buffer pollinators from nectar shortages?
AB  - Honeydew is abundant in many ecosystems and may provide an alternative food
      source (a buffer) for pollinators during periods of food shortage, but the impact
      of honeydew on pollination systems has received little attention to date. In New
      Zealand, kanuka trees (Myrtaceae: Kunzea ericoides (A. Rich) Joy Thompson) are
      often heavily infested by the endemic honeydew-producing scale insect
      Coelostomidia wairoensis (Maskell) (Hemiptera: Coelostomidiidae) and the period
      of high honeydew production can overlap with kanuka flowering. In this study, we
      quantified the sugar resources (honeydew and nectar) available on kanuka and
      recorded nocturnal insect activity on infested and uninfested kanuka during the
      flowering period. Insects were abundant on infested trees, but flowers on
      infested trees received fewer insect visitors than flowers on uninfested trees.
      There was little evidence that insects had switched directly from nectar-feeding
      to honeydew-feeding, but it is possible that some omnivores (e.g., cockroaches)
      were distracted by the other honeydew-associated resources on infested branches
      (e.g., sooty molds, prey). Additional sampling was carried out after kanuka
      flowering had finished to determine honeydew usage in the absence of adjacent
      nectar resources. Moths, which had fed almost exclusively on nectar earlier, were
      recorded feeding extensively on honeydew after flowering had ceased; hence,
      honeydew may provide an additional food source for potential pollinators. Our
      results show that honeydew resources can impact floral visitation patterns and
      suggest that future pollinator studies should consider the full range of sugar
      resources present in the study environment. 

PMID- 25368983
TI  - Superhydrophobic analyte concentration utilizing colloid-pillar array SERS
      substrates.
AB  - The ability to detect a few molecules present in a large sample is of great
      interest for the detection of trace components in both medicinal and
      environmental samples. Surface enhanced Raman spectroscopy (SERS) is a technique
      that can be utilized to detect molecules at very low absolute numbers. However,
      detection at trace concentration levels in real samples requires properly
      designed delivery and detection systems. The following work involves
      superhydrophobic surfaces that have as a framework deterministic or stochastic
      silicon pillar arrays formed by lithographic or metal dewetting protocols,
      respectively. In order to generate the necessary plasmonic substrate for SERS
      detection, simple and flow stable Ag colloid was added to the functionalized
      pillar array system via soaking. Native pillars and pillars with hydrophobic
      modification are used. The pillars provide a means to concentrate analyte via
      superhydrophobic droplet evaporation effects. A >= 100-fold concentration of
      analyte was estimated, with a limit of detection of 2.9 * 10(-12) M for
      mitoxantrone dihydrochloride. Additionally, analytes were delivered to the
      surface via a multiplex approach in order to demonstrate an ability to control
      droplet size and placement for scaled-up uses in real world applications.
      Finally, a concentration process involving transport and sequestration based on
      surface treatment selective wicking is demonstrated. 

PMID- 25368981
TI  - Papillary thyroid carcinoma in Denmark, 1996-2008: outcome and evaluation of
      established prognostic scoring systems in a prospective national cohort.
AB  - BACKGROUND: Regional as well as national series show an increasing incidence of
      thyroid cancer largely small size papillary thyroid carcinoma (PTC). Prognostic
      scoring systems have been developed, but these do not take into account the
      rapidly changing case mix, and adjustments may be required. The purposes of this
      study were to evaluate treatment outcomes and to analyze the value of older
      prognostic scoring systems tested on a relatively new, unselected national cohort
      of PTC patients. METHODS: This was a national prospective cohort study conducted
      in Denmark, which has a population of 5.5 million. RESULTS: A total of 1350
      patients were diagnosed with PTC during 1996-2008, and the median follow-up time
      was 7.9 years. The 10-year recurrence-free survival rate was 90.2%, and the 10
      year crude and cause-specific survival (CSS) rates were 83.7% and 93.8%
      respectively. By multivariate Cox regression, it was possible to confirm age,
      metastases (distant and nodal), extrathyroidal extension, and tumor size as
      predictors of mortality, whereas only nodal metastases, extrathyroidal extension,
      and tumor size were predictors of recurrence. In analyses of older prognostic
      scoring systems, a significant correlation between the risk group ranks was found
      for survival as well as recurrence. The c-index for CSS was highest for MACIS
      (0.92) and lowest for AMES (0.80). In the TNM, MACIS, and EORTC systems, most
      patients were classified as stage 1, and for these patients, the 10-year CSS rate
      was approximately 99.5%, confirming the generally excellent survival. CONCLUSION:
      This national study provides further evidence that a favorable prognosis is to be
      expected for patients diagnosed with PTC. Also, it was possible to confirm age,
      metastases, extrathyroidal extension, and tumor size as predictors of mortality,
      whereas only nodal metastases, extrathyroidal extension, and tumor size were
      predictors of recurrence. All the scoring systems evaluated were able to produce
      a highly significant risk group stratification, showing that in spite of the
      changes in the case mix of PTC, these systems are still applicable, and in fact
      contain valuable prognostic information useable for treatment planning.

PMID- 25368984
TI  - Design, structure-activity relationship, and in vivo characterization of the
      development candidate NVP-HSP990.
AB  - Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series
      which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral
      administration, and an excellent pharmacokinetic/pharmacodynamic relationship in
      vivo was developed from a commercial hit. The exploration of this series led to
      the selection of NVP-HSP990 as a development candidate. 

PMID- 25368985
TI  - Identification of potential serum proteomic biomarkers for clear cell renal cell
      carcinoma.
AB  - OBJECTIVE: To investigate discriminating protein patterns and serum biomarkers
      between clear cell renal cell carcinoma (ccRCC) patients and healthy controls, as
      well as between paired pre- and post-operative ccRCC patients. METHODS: We used
      magnetic bead-based separation followed by matrix-assisted laser desorption
      ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) to identify
      patients with ccRCC. A total of 162 serum samples were analyzed in this study,
      among which there were 58 serum samples from ccRCC patients, 40 from additional
      paired pre- and post-operative ccRCC patients (n = 20), and 64 from healthy
      volunteers as healthy controls. ClinProTools software identified several distinct
      markers between ccRCC patients and healthy controls, as well as between pre- and
      post-operative patients. RESULTS: Patients with ccRCC could be identified with a
      mean sensitivity of 88.38% and a mean specificity of 91.67%. Of 67 m/z peaks that
      differed among the ccRCC, healthy controls, pre- and post-operative ccRCC
      patients, 24 were significantly different (P<0.05). Three candidate peaks, which
      were upregulated in ccRCC group and showed a tendency to return to healthy
      control values after surgery, were identified as peptide regions of RNA-binding
      protein 6 (RBP6), tubulin beta chain (TUBB), and zinc finger protein 3 (ZFP3)
      with the m/z values of 1466.98, 1618.22, and 5905.23, respectively. CONCLUSION:
      MB-MALDI-TOF-MS method could generate serum peptidome profiles of ccRCC, and
      provide a new approach to identify potential biomarkers for diagnosis as well as
      prognosis of this malignancy.

PMID- 25368987
TI  - [International collaborative study shows sustained reduction of infant and child
      mortality rates].

PMID- 25368986
TI  - High efficiency ex vivo cloning of antigen-specific human effector T cells.
AB  - While cloned T cells are valuable tools for the exploration of immune responses
      against viruses and tumours, current cloning methods do not allow inferences to
      be made about the function and phenotype of a clone's in vivo precursor, nor can
      precise cloning efficiencies be calculated. Additionally, there is currently no
      general method for cloning antigen-specific effector T cells directly from
      peripheral blood mononuclear cells, without the need for prior expansion in
      vitro. Here we describe an efficient method for cloning effector T cells ex vivo.
      Functional T cells are detected using optimised interferon gamma capture
      following stimulation with viral or tumour cell-derived antigen. In combination
      with multiple phenotypic markers, single effector T cells are sorted using a flow
      cytometer directly into multi-well plates, and cloned using standard, non antigen
      specific expansion methods. We provide examples of this novel technology to
      generate antigen-reactive clones from healthy donors using Epstein-Barr virus and
      cytomegalovirus as representative viral antigen sources, and from two melanoma
      patients using autologous melanoma cells. Cloning efficiency, clonality, and
      retention/loss of function are described. Ex vivo effector cell cloning provides
      a rapid and effective method of deriving antigen-specific T cells clones with
      traceable in vivo precursor function and phenotype. 

PMID- 25368988
TI  - 60-Day chronic exposure to low concentrations of HgCl2 impairs sperm quality:
      hormonal imbalance and oxidative stress as potential routes for reproductive
      dysfunction in rats.
AB  - Mercury is a toxic and bio-accumulative heavy metal of global concern. While good
      deals of research have been conducted on the toxic effects of mercury, little is
      known about the mechanisms involved in the pathogenesis of male reproductive
      dysfunction induced by mercury. Therefore, the purpose of this study was to
      assess the effects and underlying mechanisms of chronic mercury exposure at low
      levels on male reproductive system of rats. Three-month-old male Wistar rats were
      divided into two groups and treated for 60 days with saline (i.m., Control) and
      HgCl2 (i.m. 1st dose: 4.6 ug/kg, subsequent doses 0.07 ug/kg/day). We analyzed
      sperm parameters, hormonal levels and biomarkers of oxidative stress in testis,
      epididymis, prostate and vas deferens. Mercury treatment decreased daily sperm
      production, count and motility and increased head and tail morphologic
      abnormalities. Moreover, mercury treatment decreased luteinizing hormone levels,
      increased lipid peroxidation on testis and decreased antioxidant enzymes
      activities (superoxide dismutase and catalase) on reproductive organs. Our data
      demonstrate that 60-day chronic exposure to low concentrations of HgCl2 impairs
      sperm quality and promotes hormonal imbalance. The raised oxidative stress seems
      to be a potential mechanism involved on male reproductive toxicity by mercury. 

PMID- 25368989
TI  - Diagnostics for stochastic genome-scale modeling via model slicing and debugging.
AB  - Modeling of biological behavior has evolved from simple gene expression plots
      represented by mathematical equations to genome-scale systems biology networks.
      However, due to obstacles in complexity and scalability of creating genome-scale
      models, several biological modelers have turned to programming or scripting
      languages and away from modeling fundamentals. In doing so, they have traded the
      ability to have exchangeable, standardized model representation formats, while
      those that remain true to standardized model representation are faced with
      challenges in model complexity and analysis. We have developed a model diagnostic
      methodology inspired by program slicing and debugging and demonstrate the
      effectiveness of the methodology on a genome-scale metabolic network model
      published in the BioModels database. The computer-aided identification revealed
      specific points of interest such as reversibility of reactions, initialization of
      species amounts, and parameter estimation that improved a candidate cell's
      adenosine triphosphate production. We then compared the advantages of our
      methodology over other modeling techniques such as model checking and model
      reduction. A software application that implements the methodology is available at
      http://gel.ym.edu.tw/gcs/. 

PMID- 25368990
TI  - Functional analysis of prognostic gene expression network genes in metastatic
      breast cancer models.
AB  - Identification of conserved co-expression networks is a useful tool for
      clustering groups of genes enriched for common molecular or cellular functions
      [1]. The relative importance of genes within networks can frequently be inferred
      by the degree of connectivity, with those displaying high connectivity being
      significantly more likely to be associated with specific molecular functions [2].
      Previously we utilized cross-species network analysis to identify two network
      modules that were significantly associated with distant metastasis free survival
      in breast cancer. Here, we validate one of the highly connected genes as a
      metastasis associated gene. Tpx2, the most highly connected gene within a
      proliferation network specifically prognostic for estrogen receptor positive
      (ER+) breast cancers, enhances metastatic disease, but in a tumor autonomous,
      proliferation-independent manner. Histologic analysis suggests instead that
      variation of TPX2 levels within disseminated tumor cells may influence the
      transition between dormant to actively proliferating cells in the secondary site.
      These results support the co-expression network approach for identification of
      new metastasis-associated genes to provide new information regarding the etiology
      of breast cancer progression and metastatic disease.

PMID- 25368991
TI  - The dinoflagellate Lingulodinium polyedrum responds to N depletion by a polarized
      deposition of starch and lipid bodies.
AB  - Dinoflagellates are important contributors to the marine phytoplankton and global
      carbon fixation, but are also infamous for their ability to form the spectacular
      harmful algal blooms called red tides. While blooms are often associated with
      high available nitrogen, there are instances where they are observed in
      oligotrophic environments. In order to maintain their massive population in
      conditions of nitrogen limitation, dinoflagellates must have evolved efficient
      adaptive mechanisms. Here we report the physiological responses to nitrogen
      deprivation in Lingulodinium polyedrum. We find that this species reacts to
      nitrogen stress, as do most plants and microalgae, by stopping cell growth and
      diminishing levels of internal nitrogen, in particular in the form of protein and
      chlorophyll. Photosynthesis is maintained at high levels for roughly a week
      following nitrate depletion, resulting in accumulated photosynthetic products in
      the form of starch. During the second week, photosynthesis rates decrease due to
      a reduction in the number of chloroplasts and the accumulation of neutral lipid
      droplets. Surprisingly, the starch granules and lipid droplets are seen to
      accumulate at opposite poles of the cell. Lastly, we observe that cells
      acclimated to nitrogen-depleted conditions resume normal growth after addition of
      inorganic nitrogen, but are able to maintain high cell densities far longer than
      cells grown continuously in nitrogen-replete conditions. 

PMID- 25368992
TI  - No difference in the rate of change in telomere length or telomerase activity in
      HIV-infected patients after three years of darunavir/ritonavir with and without
      nucleoside analogues in the MONET trial.
AB  - OBJECTIVE: To determine whether nucleos(t)ide reverse transcriptase inhibitors
      (NRTI) contribute to an accelerated loss in telomere length (TL) in HIV-infected
      patients on antiretroviral therapy (ART). DESIGN: Substudy of randomised
      controlled trial. METHODS: Patients with HIV RNA <50 copies/mL on combination ART
      (n = 256) were randomised to darunavir/ritonavir (DRV/r) 800/100 mg once daily,
      either as monotherapy (n = 127) or with 2 NRTIs (n = 129) for up to 144 weeks. TL
      and telomerase activity was quantified on stored peripheral blood mononuclear
      cells (PBMC; n = 124) using quantitative real time PCR. RESULTS: Patients in the
      sub-study had a mean age of 44 years and had received NRTI for a mean of 6.4
      years (range 1-20 years). As expected, older patients have significantly shorter
      TL (p = 0.006), while women had significantly longer TL (p = 0.026). There was no
      significant association between TL and either the duration of prior NRTI
      treatment (p = 0.894) or the use of a PI versus NNRTI (p = 0.107). There was no
      significant difference between patients who continued or ceased NRTI in the mean
      change/year of TL or telomerase (p = 0.580 and 0.280 respectively). CONCLUSION:
      Continuation versus cessation of NRTI treatment was not associated with an
      accelerated loss in TL or telomerase activity.

PMID- 25368993
TI  - Regulation of RAB5C is important for the growth inhibitory effects of MiR-509 in
      human precursor-B acute lymphoblastic leukemia.
AB  - MicroRNAs (miRs) regulate essentially all cellular processes, but few miRs are
      known to inhibit growth of precursor-B acute lymphoblastic leukemias (B-ALLs). We
      identified miR-509 via a human genome-wide gain-of-function screen for miRs that
      inhibit growth of the NALM6 human B-ALL cell line. MiR-509-mediated inhibition of
      NALM6 growth was confirmed by 3 independent assays. Enforced miR-509 expression
      inhibited 2 of 2 additional B-ALL cell lines tested, but not 3 non-B-ALL leukemia
      cell lines. MiR-509-transduced NALM6 cells had reduced numbers of actively
      proliferating cells and increased numbers of cells undergoing apoptosis. Using
      miR target prediction algorithms and a filtering strategy, RAB5C was predicted as
      a potentially relevant target of miR-509. Enforced miR-509 expression in NALM6
      cells reduced RAB5C mRNA and protein levels, and RAB5C was demonstrated to be a
      direct target of miR-509. Knockdown of RAB5C in NALM6 cells recapitulated the
      growth inhibitory effects of miR-509. Co-expression of the RAB5C open reading
      frame without its 3' untranslated region (3'UTR) blocked the growth-inhibitory
      effect mediated by miR-509. These findings establish RAB5C as a target of miR-509
      and an important regulator of B-ALL cell growth with potential as a therapeutic
      target. 

PMID- 25368994
TI  - Identification of most stable endogenous control genes for microRNA
      quantification in the developing mouse lung.
AB  - MicroRNAs (miRNAs) are endogenous small non coding RNAs acting as negative
      regulators. miRNA are involved in lung development and pulmonary diseases.
      Measurement of their levels by qPCR is directly influenced by the stability of
      normalization gene(s), which can be affected by the experimental conditions. The
      developing lung is a changing tissue and one normalization gene showing stability
      on one developmental day may be modulated over time. Moreover, some developmental
      events are affected by sex, which also has to be considered. In this study, we
      compared stability of five putative control genes in the lung between sexes from
      the pseudoglandular to the alveolar stages and in adult lungs. Expression of
      sno135, sno142, sno202, sno234, and sno251 was studied by qPCR in male and female
      lung samples collected at seven time points from GD 15.5 to PN 30. Cq values of
      sno251 showed the highest variation across the different developmental stages,
      while sno234 was the most stable gene. Gene expression stability was studied by
      geNorm, NormFinder and BestKeeper. Our data showed that ranking of genes based on
      expression stability changed according to developmental time and sex.
      sno135/sno234 and sno142/sno234 were proposed as best combinations of
      normalization genes when both sexes and all the studied developmental stages are
      considered. Normalization of let7-a RNA levels with different pairs of control
      genes proposed by geNorm and NormFinder gave similar data, while the use of less
      stable genes introduced a statistically significant difference on PN 0. In
      conclusion, variations in stability of normalization gene expression are observed
      over time and according to sex during lung development. Best pairs of
      normalization genes are presented for specific developmental stages, and for the
      period extending from the pseudoglandular to the alveolar stages. The use of
      normalization genes selected for their expression stability is essential in lung
      development studies. 

PMID- 25368995
TI  - Hormonal and neuromuscular responses to mechanical vibration applied to upper
      extremity muscles.
AB  - OBJECTIVE: To investigate the acute residual hormonal and neuromuscular responses
      exhibited following a single session of mechanical vibration applied to the upper
      extremities among different acceleration loads. METHODS: Thirty male students
      were randomly assigned to a high vibration group (HVG), a low vibration group
      (LVG), or a control group (CG). A randomized double-blind, controlled-parallel
      study design was employed. The measurements and interventions were performed at
      the Laboratory of Biomechanics of the University of L'Aquila. The HVG and LVG
      participants were exposed to a series of 20 trials *10 s of synchronous whole
      body vibration (WBV) with a 10-s pause between each trial and a 4-min pause after
      the first 10 trials. The CG participants assumed an isometric push-up position
      without WBV. The outcome measures were growth hormone (GH), testosterone, maximal
      voluntary isometric contraction during bench-press, maximal voluntary isometric
      contraction during handgrip, and electromyography root-mean-square (EMGrms)
      muscle activity (pectoralis major [PM], triceps brachii [TB], anterior deltoid
      [DE], and flexor carpi radialis [FCR]). RESULTS: The GH increased significantly
      over time only in the HVG (P = 0.003). Additionally, the testosterone levels
      changed significantly over time in the LVG (P = 0.011) and the HVG (P = 0.001).
      MVC during bench press decreased significantly in the LVG (P = 0.001) and the HVG
      (P = 0.002). In the HVG, the EMGrms decreased significantly in the TB (P = 0.006)
      muscle. In the LVG, the EMGrms decreased significantly in the DE (P = 0.009) and
      FCR (P = 0.006) muscles. CONCLUSION: Synchronous WBV acutely increased GH and
      testosterone serum concentrations and decreased the MVC and their respective
      maximal EMGrms activities, which indicated a possible central fatigue effect.
      Interestingly, only the GH response was dependent on the acceleration with
      respect to the subjects' responsiveness.

PMID- 25368996
TI  - L-Glutamate supplementation improves small intestinal architecture and enhances
      the expressions of jejunal mucosa amino acid receptors and transporters in
      weaning piglets.
AB  - L-Glutamate is a major oxidative fuel for the small intestine. However, few
      studies have demonstrated the effect of L-glutamate on the intestinal
      architecture and signaling of amino acids in the small intestine. The aim of this
      study was to investigate the effects of dietary L-glutamate supplementation on
      the intestinal architecture and expressions of jejunal mucosa amino acid
      receptors and transporters in weaning piglets. A total of 120 weaning piglets
      aged 35 +/- 1 days with an average body weight at 8.91 +/- 0.45 kg were randomly
      allocated to two treatments with six replicates of ten piglets each, fed with
      diets containing 1.21% alanine, or 2% L-glutamate. L-Glutamate supplementation
      increased the activity of glutamate oxaloacetate transaminase (GOT) in the
      jejunal mucosa. Also, the mRNA expression level of jejunal mucosa glutamine
      synthetase (GS) was increased by L-glutamate supplementation. The height of villi
      in duodenal and jejunal segments, and the relative mRNA expression of occludin
      and zonula occludens protein-1 (ZO-1) in jejunal mucosa were increased by dietary
      L-glutamate supplementation. L-Glutamate supplementation increased plasma
      concentrations of glutamate, arginine, histidine, isoleucine, leucine,
      methionine, phenylalanine and threonine. L-Glutamate supplementation also
      increased the relative mRNA expression of the jejunal mucosa Ca(2+)-sensing
      receptor (CaR), metabotropic glutamate receptor 1 (mGluR1) and metabotropic
      glutamate receptor 4 (mGluR4), and neutral amino acid transporter B(0)-like
      (SLC1A5) in the jejunal mucosa. These findings suggest that dietary addition of
      2% L-glutamate improves the intestinal integrity and influences the expression of
      amino acid receptors and transporters in the jejunum of weaning, which is
      beneficial for the improvement of jejunal nutrients for digestion and absorption.

PMID- 25368997
TI  - Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with
      novel virulence-enhancing markers.
AB  - PB1-F2 protein, expressed from an alternative reading frame of most influenza A
      virus (IAV) PB1 segments, may possess specific residues associated with enhanced
      inflammation (L62, R75, R79, and L82) and cytotoxicity (I68, L69, and V70). These
      residues were shown to increase the pathogenicity of primary viral and secondary
      bacterial infections in a mouse model. In contrast to human seasonal influenza
      strains, virulence-associated residues are present in PB1-F2 proteins from
      pandemic H1N1 1918, H2N2 1957, and H3N2 1968, and highly pathogenic H5N1 strains,
      suggesting their contribution to viruses' pathogenic phenotypes. Non-human
      influenza strains may act as donors of virulent PB1-F2 proteins. Previously,
      avian influenza strains were identified as a potential source of inflammatory,
      but not cytotoxic, PB1-F2 residues. Here, we analyze the frequency of virulence
      associated residues in PB1-F2 sequences from IAVs circulating in mammalian
      species in close contact with humans: pigs, horses, and dogs. All four
      inflammatory residues were found in PB1-F2 proteins from these viruses. Among
      cytotoxic residues, I68 was the most common and was especially prevalent in
      equine and canine IAVs. Historically, PB1-F2 from equine (about 75%) and canine
      (about 20%) IAVs were most likely to have combinations of the highest numbers of
      residues associated with inflammation and cytotoxicity, compared to about 7% of
      swine IAVs. Our analyses show that, in addition to birds, pigs, horses, and dogs
      are potentially important sources of pathogenic PB1-F2 variants. There is a need
      for surveillance of IAVs with genetic markers of virulence that may be emerging
      from these reservoirs in order to improve pandemic preparedness and response. 

PMID- 25368998
TI  - Biochemical, biophysical and IgE-epitope characterization of the wheat food
      allergen, Tri a 37.
AB  - Wheat is an important staple food and potent allergen source. Recently, we
      isolated a cDNA coding for wheat alpha-purothionin which is recognized by wheat
      food allergic patients at risk for severe wheat-induced allergy. The purpose of
      the present study was the biochemical, biophysical and IgE epitope
      characterization of recombinant alpha-purothionin. Synthetic genes coding for
      alpha-purothionin were expressed in a prokaryotic system using Escherichia coli
      and in a eukaryotic expression system based on baculovirus-infected Sf9-insect
      cells. Recombinant proteins were purified and characterized by SDS-PAGE, mass
      spectrometry, circular dichroism, chemical cross-linking and size exclusion
      chromatography. Five overlapping peptide were synthesized for epitope mapping.
      Alpha-purothionin-specific rabbit antibodies were raised to perform IgE
      inhibition experiments and to study the resistance to digestion. The IgE
      reactivity of the proteins and peptides from ten wheat food allergic patients was
      studied in non-denaturing RAST-based binding assays. Alpha-purothionin was
      expressed in the prokaryotic (EcTri a 37) and in the eukaryotic system (BvTri a
      37) as a soluble and monomeric protein. However, circular dichroism analysis
      revealed that EcTri a 37 was unfolded whereas BvTri a 37 was a folded protein.
      Both proteins showed comparable IgE-reactivity and the epitope mapping revealed
      the presence of sequential IgE epitopes in the N-terminal basic thionin domain
      (peptide1:KSCCRSTLGRNCYNLCRARGAQKLCAGVCR) and in the C-terminal acidic extension
      domain (peptide3:KGFPKLALESNSDEPDTIEYCNLGCRSSVC,
      peptide4:CNLGCRSSVCDYMVNAAADDEEMKLYVEN). Natural Tri a 37 was digested under
      gastric conditions but resistant to duodenal digestion. Immunization with EcTri a
      37 induced IgG antibodies which recognized similar epitopes as IgE antibodies
      from allergic patients and inhibited allergic patients' IgE binding. Reactivity
      to Tri a 37 does not require a folded protein and the presence of sequential IgE
      epitopes indicates that sensitization to alpha-purothionin occurs via the gut.
      Both allergens can be used for in-vitro diagnosis of wheat food allergy. The
      induction of blocking IgG antibodies suggests the usefulness for immunotherapy.

PMID- 25368999
TI  - Trajectories of metabolic syndrome development in young adults.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a constellation of metabolic aberrations
      that collectively increase the risk for cardiovascular disease and type 2
      diabetes. Greater understanding of MetS developments may provide insight into
      targeted prevention strategies for individuals at greatest risk. The purpose of
      this study was to i) identify distinct patterns of longitudinal MetS development
      and; ii) develop a character profile that differentiates groups by level of MetS
      risk. METHODS AND RESULTS: Data from the Coronary Artery Risk Development in
      Young Adults (CARDIA) study (n = 3 804; 18-30 y) was obtained by limited access
      application from the National Heart, Lung, and Blood Institute and used for this
      analysis. MetS, as defined by the Harmonized criteria, was assessed over a 20
      year follow-up period. Group-level trajectory analysis identified 4 distinct
      groups with varying rates of component development [No (23.8% of sample); Low
      (33.5%); Moderate (35.3%); and High MetS (7.4%)]. After adjusting for covariates,
      individuals in the At-Risk groups (Low, Moderate and High MetS) were more likely
      to be of black ethnicity (1.37, 1.14-1.66), have a family history of
      cardiovascular disease (1.61, 1.31-1.97) and history of dieting (1.69, 1.20-2.39)
      when compared to the No Risk trajectory group (No MetS). Conversely, increasing
      baseline education (0.76, 0.65-0.89) and aerobic fitness (0.55, 0.47-0.64) was
      inversely associated with At-Risk group membership. CONCLUSIONS: Results suggest
      distinct profiles of MetS development that can be identified by baseline risk
      factors. Further research is necessary to understand the clinical implication of
      intermediate MetS development groups with respect to overall cardiometabolic
      risk.

PMID- 25369001
TI  - Profile and treatment outcomes of tuberculosis in the elderly in southeastern
      Nigeria, 2011-2012.
AB  - BACKGROUND: The demographic transition and increasing life expectancy in Africa
      has lead to a rising elderly population. In Nigeria, little is known about the
      profile of and treatment outcomes of tuberculosis (TB) in the elderly. METHODS:
      Retrospective cohort study of adult TB patients treated between January 2011 and
      December 2012 in two large health facilities in Nigeria. The demographic,
      clinical and treatment outcomes of patients aged 60 and older were compared with
      those aged 15 to 59 years. RESULTS: Elderly (>= 60 years) TB patients accounted
      for 12.7% of all (1668) adult TB enrolled. Elderly patients had a higher
      proportion of men compared to non-elderly (64.2% vs 56.8%; p = 0.043); but a
      lower proportion of smear-positive TB at baseline (40.7% vs 65.8%; p<0.001). A
      higher proportion of elderly patients failed to smear convert after the intensive
      phase of treatment (23.7% vs 19.8%; p = 0.06), and overall elderly patients had
      lower treatment success rates (68.9% vs 77.1%; p = 0.009). Unsuccessful outcomes
      were mainly due to higher default and deaths in the elderly. The risk factors for
      unsuccessful outcomes in the elderly were: extrapulmonary TB case (adjusted odds
      ratio (aOR) 10.9; 95% confidence interval (CI) 1.1-108), and HIV co-infection
      (aOR 3.6; CI 1.1-11.7). CONCLUSIONS: Treatment outcomes of elderly TB patients
      were inferior to non-elderly adults with higher death and default rates being
      implicated. With the rising elderly population, specific strategies are needed to
      quickly address TB management in the elderly in resource-limited settings.

PMID- 25369003
TI  - Presence of C1-inhibitor polymers in a subset of patients suffering from
      hereditary angioedema.
AB  - Hereditary angioedema (HAE) is a potentially life-threatening disease caused by
      mutations in the gene encoding the serine protease inhibitor (serpin) C1
      inhibitor (C1-inh). The mutations cause decreased functional plasma levels of C1
      inh, which triggers unpredictable recurrent edema attacks. Subjects suffering
      from HAE have been classified in type I patients with decreased functional and
      antigenic levels of C1-inh, and type II patients with decreased functional but
      normal antigenic C1-inh levels. However, a few reports have demonstrated that
      some mutations cause C1-inh polymerization in vitro, and it is speculated that C1
      inh polymers may exist in patient plasma, challenging the current classification
      of HAE patients. To investigate the presence of C1-inh polymers in patient plasma
      samples, we developed an immunological method, where monoclonal antibodies
      produced against polymerized C1-inh were applied in native PAGE western blotting.
      Using this approach we analyzed genuine plasma samples from 31 Danish HAE
      families, and found that plasma samples from three genotypically distinct HAE
      type I families (classified upon C1-inh plasma concentrations) contained C1-inh
      polymers. Identical C1-inh polymerization phenotypes were observed in four
      affected family members from one of these families. Genotyping of the families
      revealed that the polymerogenic mutations of two families were located in
      proximity to the reactive center loop insertion site in C1-inh (p.Ile271Thr and
      p.Ser258_Pro260del),and one mutation affected helix C (p.Thr167Asn). In
      conclusion, we demonstrate that C1-inh polymers are present in the plasma of a
      subgroup of HAE type I patients. 

PMID- 25369000
TI  - Structural and mechanistic basis of zinc regulation across the E. coli Zur
      regulon.
AB  - Commensal microbes, whether they are beneficial or pathogenic, are sensitive to
      host processes that starve or swamp the prokaryote with large fluctuations in
      local zinc concentration. To understand how microorganisms coordinate a dynamic
      response to changes in zinc availability at the molecular level, we evaluated the
      molecular mechanism of the zinc-sensing zinc uptake regulator (Zur) protein at
      each of the known Zur-regulated genes in Escherichia coli. We solved the
      structure of zinc-loaded Zur bound to the P(znuABC) promoter and show that this
      metalloregulatory protein represses gene expression by a highly cooperative
      binding of two adjacent dimers to essentially encircle the core element of each
      of the Zur-regulated promoters. Cooperativity in these protein-DNA interactions
      requires a pair of asymmetric salt bridges between Arg52 and Asp49' that connect
      otherwise independent dimers. Analysis of the protein-DNA interface led to the
      discovery of a new member of the Zur-regulon: pliG. We demonstrate this gene is
      directly regulated by Zur in a zinc responsive manner. The pliG promoter forms
      stable complexes with either one or two Zur dimers with significantly less
      protein-DNA cooperativity than observed at other Zur regulon promoters.
      Comparison of the in vitro Zur-DNA binding affinity at each of four Zur-regulon
      promoters reveals ca. 10,000-fold variation Zur-DNA binding constants. The degree
      of Zur repression observed in vivo by comparison of transcript copy number in
      wild-type and Deltazur strains parallels this trend spanning a 100-fold
      difference. We conclude that the number of ferric uptake regulator (Fur)-family
      dimers that bind within any given promoter varies significantly and that the
      thermodynamic profile of the Zur-DNA interactions directly correlates with the
      physiological response at different promoters.

PMID- 25369004
TI  - Discovery and analysis of microRNAs in Leymus chinensis under saline-alkali and
      drought stress using high-throughput sequencing.
AB  - Leymus chinensis (Trin.) Tzvel. is a perennial rhizome grass of the Poaceae (also
      called Gramineae) family, which adapts well to drought, saline and alkaline
      conditions. However, little is known about the stress tolerance of L. chinensis
      at the molecular level. microRNAs (miRNAs) are known to play critical roles in
      nutrient homeostasis, developmental processes, pathogen responses, and abiotic
      stress in plants. In this study, we used Solexa sequencing technology to generate
      high-quality small RNA data from three L. chinensis groups: a control group, a
      saline-alkaline stress group (100 mM NaCl and 200 mM NaHCO3), and a drought
      stress group (20% polyethylene glycol 2000). From these data we identified 132
      known miRNAs and 16 novel miRNAs candidates. For these miRNAs we also identified
      target genes that encode a broad range of proteins that may be correlated with
      abiotic stress regulation. This is the first study to demonstrate differentially
      expressed miRNAs in L. chinensis under saline-alkali and drought stress. These
      findings may help explain the saline-alkaline and drought stress responses in L.
      chinensis. 

PMID- 25369005
TI  - Evaluation of the expression of P-glycoprotein in propoxur-resistant Caco-2
      cells.
AB  - There is a great concern about the effect of propoxur, as one of the more common
      N-methyl carbamate pesticides, on human health due to its extensive use in
      agricultural and non-agricultural applications. Caco-2 cells became resistant to
      propoxur, and the resistance was confirmed through MTT assay. Then the cell
      membrane integrity and P-glycoprotein expression were measured by LDH assay and
      western blot analysis, respectively and compared to the parent cells.  Contrary
      to what was expected, the expression of P-glycoprotein in propoxur resistant
      cells was lower than parent cells. CONCLUSION: This study indicates that the
      resistance to propoxur may not be related to P-glycoprotein expression directly,
      since P-glycoprotein expression has decreased in these cells.

PMID- 25369006
TI  - Melatonin decreases olanzapine induced metabolic side-effects in adolescents with
      bipolar disorder: a randomized double-blind placebo-controlled trial.
AB  - Olanzapine is the frequently prescribed drug in children and adolescents with
      bipolar disorder, but unfortunately it has metabolic side-effects. On the other
      hand, in a number of melatonin studies on sleep cycle, regulation of metabolic
      abnormalities has been reported. Therefore, we aimed to study effects of
      melatonin in reducing metabolic side-effects of olanzapine in 11-17 year-old
      patients with bipolar disorder. Seventy-seven 11-17 year-old outpatients entered
      into the study after their initial diagnosis of bipolar mood disorder by a
      psychiatrist. After assessing inclusion and exclusion criteria, 48 patients
      consented to participate in the study. Of this number, 24 patients were allocated
      to olanzapine, lithium carbonate, and melatonin and 24 patients were allocated to
      olanzapine, lithium carbonate, and placebo. Young mania rating scale was
      performed at baseline. Before treatment initiation and at sixth and twelfth weeks
      after treatment, Lipid profile, Fasting Blood Sugar (FBS), Systolic Blood
      Pressure (SBP) and Diastolic Blood Pressure (DBP) were measured. ANOVA with
      repeated measure and independent sample t-test were used for data analysis.
      Nineteen patients in each group completed the study and yielded data for
      analysis.  ANOVA with repeated measure showed that FBS and Triglyceride (TG)
      (especially in boys) demonstrated greater increase in the placebo group compared
      to the melatonin group but the differences were not statistically significant.
      Melatonin significantly inhibited the rise in Total Cholesterol levels compared
      to placebo (P=0.032). Mean SBP rose more slowly in the melatonin group (1.05mmHg)
      compared to placebo (6.36 mmHg) (P=0.023). The trends in DBP did not show any
      significant pattern. Administration of melatonin along with olanzapine and
      lithium carbonate could significantly inhibit the rise in cholesterol level and
      SBP compared to placebo. The effect of melatonin on TG was more obvious in boys.
      Melatonin was more effective in prevention of SBP rise. 

PMID- 25369007
TI  - Association of SNPs in interferon receptor genes in chronic hepatitis C with
      response to combined therapy of interferon and ribavirin.
AB  - Hepatitis C Virus is one of the main reasons for chronic liver disease and
      hepatocellular carcinoma. Combination therapy with Interferon (peg-IFN-alpha) and
      Ribavirin (RBV) clear the virus more likely than the others. Different factors
      like virus and host characteristics influence on response to treatment. The most
      important viral factors include virus genotype and viral load; host factors like
      genetic, gender, race, age, weight and liver enzymes are also important. Previous
      studies have shown that single nucleotide polymorphisms (SNPs) in IFNR genes can
      regulate and influence on treatment with IFN. The purpose of this study is to
      investigate the association between SNPs in IFN-alpha receptor (IFNAR1 & IFNAR2)
      genes among subjects affected with chronic hepatitis C, who have treated with IFN
      and RBV, and also relationship between HCV genotypes and response to combination
      antiviral therapy. Peripheral blood mononuclear cells (PBMCs) were taken from
      whole blood of 61 patients affected with chronic hepatitis C who were treated
      with IFN and Ribavirin. Then, DNA was extracted from PBMCs and quality of DNA was
      assessed with Nanodrop finally two SNPs [Ex4-30G>C] and [Ivs1-4640 G>A] of IFN
      receptor genes (IFNAR1 and IFNAR2) were measured by TaqMan Real-Time PCR in ABi
      Prism 7900 system. Also to confirm the response rate to therapy, RNA was
      extracted then RT PCR was performed and final product was studied with gel
      electrophoresis and UV spectroscopy. Statistical analysis was performed using
      SPSS version 18.0 for Windows. The analysis of results from TaqMan SNP Genotyping
      has been shown that two SNPs (Ex4-30G>C and Ivs1-4640 G>A) of IFNAR1 and IFNAR2
      didn't show any relationship with response to combined therapy in subjects
      affected with chronic hepatitis C who have treated with peg-IFN-alpha and
      Ribavirin. 61 patients complete the treatment period. 54 patients (%88/5) of them
      responded to treatment and 7 patients (%11/5) did not. Research and data analysis
      have shown that there is no significant relationship between sex (P=0 /7) and age
      (P=0 /2). But there is a relationship between genotype-3a and response to
      combined therapy of IFN-alpha and RBV (0/02). Studies have shown that gene
      polymorphisms in IVSS1-22G location of IFNAR1 gene had a relationship with IFN
      treatment response. But current study has shown that there is no significant
      relationship between two SNPs Ex4-30G>C and Ivs1-4640 G>A and response to IFN
      therapy. In continue we suggest that it would be better to use this technique to
      evaluate other SNPs in IFN genes. 

PMID- 25369008
TI  - Comparison of clinical features of Behcet disease according to age in a Tunisian
      cohort.
AB  - Behcet's disease (BD) is a multisystemic inflammatory disease that occurs most
      often between the second and fourth decade of life. Patients have been reported
      during the first months of life and after 70 years. Our objective was to
      determine the clinical, paraclinical and genetic characteristics of BD in
      patients aged < 20 and > 40 years. We conducted a comparative retrospective study
      including patients with BD (Criteria of International Study Group on BD).
      Patients were divided into two groups: those < 20 years (Group one) and those >
      40 years (Group two). The clinical, paraclinical and genetic (HLA)
      characteristics were determined and compared in the two groups. The data were
      compiled and analyzed using SPSS 11.0. Thirty totals of 430 patients were
      included. Group one included 81 patients (55 men and 26 women). Group two
      included 68 patients (45 men and 23 women). Cutaneous involvement (88.9 versus
      76.5%; P=0.043), pseudofolliculitis (84 versus 64.5%; P=0.004) and vena cava
      thrombosis (11.11 vs 0%; P=0.004) were significantly more frequent in group one
      while joint involvements were more common in group two (57.4 versus 40.7%; P=
      0.043). The frequency of erythema nodosum as well as ocular, vascular and
      neurological disorders was comparable between the two groups. Few studies in the
      literature have compared the clinical, paraclinical and genetic characteristics
      of BD, who had first symptom onset after 40 years of age. Late-onset BD, usually,
      affects both genders equally. According to present results, the frequency of
      severe organ involvement is equal regardless of age, except for vena cava
      thrombosis. 

PMID- 25369009
TI  - Congenital hypothyroidism: etiology and growth-development outcome.
AB  - One of the most preventable causes of mental and growth retardation is congenital
      hypothyroidism (CH). This study tries to investigate growth and mental outcome of
      patients with CH. Since November 2006 and November 2007 in Guilan province, north
      of Iran, all neonates who were diagnosed with CH, evaluated for etiology of CH by
      laboratory follow up, thyroid sonography or scan. Growth and development of
      patients with CH were compared with healthy children in same age, geographical
      area, social and economical classes in four years old. Demographic
      characteristics including height, weight, and head circumference at birth, follow
      up time (four years old) and IQ (Good enough test) were recorded in
      questionnaires. Among 28904 screened neonates, 37 patients with CH were
      diagnosed. Incidence of CH was 1:781 in live births, 20 (54%) in female neonates
      and 17 (46%) in male neonates. The incidences of permanent and transient
      hypothyroidism were 43.2% (16 cases) and 56. 8% (21 cases) respectively. The
      incidence of permanent and transient hypothyroidism were 16 (43.2%) and 21 (56,
      8%), respectively. In permanent CH, 11 cases (%.68.2) had dyshormonogenesis and 5
      cases (%.31.2) had thyroid dysgenesis. Significant statistical difference was
      only in family history of thyroid disease (34, 3% Positive family history in CH
      vs. 13.2% in control group, P-value 0.03). All other demographic characteristics
      and IQ had no statistical difference. Patients with CH diagnosed through neonatal
      screening and treated had normal growth as general population that indicates
      effective screening program and treatment in this area (3.2%). 

PMID- 25369010
TI  - Investigating the productivity model for clinical nurses.
AB  - One of the main objectives of quantitative researches is assessment of models
      developed by qualitative studies. Models validation through their testing implies
      that the designed model is representative of the existed facts. Hence, this study
      was conducted to assess the clinical nurses' productivity model presented for
      Iranian nurses' productivity. The sample of the study consisted of 360 nurses of
      Tehran University of Medical Sciences. The research tool was a questionnaire for
      measuring the components of clinical nurses' productivity. After completing all
      steps of instrument psychometric and getting answers from the participants, the
      factors introduced in the questionnaire were named and then Lisrel Path Analysis
      tests were performed to analyze the components of the model. The results of the
      model test revealed there is an internal relationship among different components
      of the model. Regression Analysis showed that each increasing unit in components
      of the model was to be added to central variable of productivity model -human
      resource. Model components altogether explained 20 % of clinical nurses'
      productivity variance. This study found that the important component of
      productivity is human resources that are reciprocally related to other components
      of the model. Therefore, it can be stated that the managers can promote the
      productivity by using efficient strategies to correct human resource patterns. 

PMID- 25369011
TI  - A comparison between Kaplan-Meier and weighted Kaplan-Meier methods of five-year
      survival estimation of patients with gastric cancer.
AB  - The 5-year survival rate is a good prognostic indicator for patients with Gastric
      cancer that is usually estimated based on Kaplan-Meier. In situations where
      censored observations are too many, this method produces biased estimations. This
      study aimed to compare estimations of Kaplan-Meier and Weighted Kaplan-Meier as
      an alternative method to deal with the problem of heavy-censoring. Data from 330
      patients with Gastric cancer who had undergone surgery at Iran Cancer Institute
      from 1995- 1999 were analyzed. The Survival Time of these patients was determined
      after surgery, and the 5-year survival rate for these patients was evaluated
      based on Kaplan-Meier and Weighted Kaplan-Meier methods. A total of 239 (72.4%)
      patients passed away by the end of the study and 91(27.6%) patients were
      censored. The mean and median of survival time for these patients were 24.86+/
      23.73 and 16.33 months, respectively. The one-year, two-year, three-year, four
      year, and five-year survival rates of these patients with standard error
      estimation based on Kaplan-Meier were 0.66 (0.0264), 0.42 (0.0284), 0.31
      (0.0274), 0.26 (0.0264) and 0.21 (0.0256) months, respectively. The estimations
      of Weighted Kaplan-Meier for these patients were 0.62 (0.0251), 0.35 (0.0237),
      0.24 (0.0211), 0.17 (0.0172), and 0.10 (0.0125) months, consecutively. In cases
      where censoring assumption is not made, and the study has many censored
      observations, estimations obtained from the Kaplan-Meier are biased and are
      estimated higher than its real amount. But Weighted Kaplan-Meier decreases bias
      of survival probabilities by providing appropriate weights and presents more
      accurate understanding. 

PMID- 25369012
TI  - A planning model for expansion and stagnation of higher education in Iran.
AB  - Iran universities of medical sciences have experienced a period of expansion in
      past decades. Now previous concerns are alleviated, and the former quantity-based
      policy has given a way to a more quality-seeking attitude. In this study, we
      developed a planning model for expansion and stagnation of higher education in
      Iranian universities of medical sciences based on workforce requirements of the
      country and capabilities of the universities. The plan provided an objectively
      documented base for the authorities to decide on developmental limits of
      universities. We devised guidelines for justifying existing programs within
      universities, assigning new undergraduate and postgraduate programs to
      universities, voluntary request of universities to cancel a program, and their
      request to offer new programs for the first time in the country, based on three
      factors: university educational status, each university-program educational
      status and the nation's need for each discipline. Related councils of the
      Ministry of Health and Medical Education legitimately approved the plan and
      guidelines. In this article, we introduced the methodology of developing the
      plan, described it and its related guidelines and discussed challenges and
      limitations we encountered in design and application phases. 

PMID- 25369013
TI  - Outcome of intracoronary shunt in off-pump coronary artery bypass surgery in
      patients with low cardiac output.
AB  - Patients with coronary artery disease and left ventricular dysfunction have high
      mortality with non surgical (medical) treatment. Coronary artery bypass grafting
      improves survival and the quality of life. Recently, revascularization without
      cardiopulmonary bypass has been presented as a viable alternative. The aim of
      this study was to survey the result of coronary artery bypass grafting with off
      pump technique using intracoronary shunt in patients with left ventricular
      ejection fraction<= 25%. From January 2009 to December 2012, 86 patients with an
      ejection fraction <= 25% (58 males, 28 females) aged 41- 84 years (61.2 +/- 3.1
      yrs) underwent coronary artery bypass graft surgery with off-pump technique.
      Grafting was performed as needed with internal mammary artery and saphenous vein.
      We studied operative and postoperative data. Hospital Mortality was 2.32% (two
      patients). Postoperative complications were low. Total length of hospital stay
      was 7.2 days, length of ICU stay 2.1 days pulmonary complications 3.48% (three
      patients), postoperative bleeding 340, acute renal failure 1.16% (one patient)
      and left-ventricle ejection fraction before discharge was increased about 10% in
      these patients. Coronary artery bypass grafting without cardiopulmonary bypass
      with intracoronary shunt in patients with severe left ventricular dysfunction is
      valid and safe and has low mortality and morbidity.

PMID- 25369014
TI  - Study guides: effective tools to improve self-directed learning skills of medical
      students.
AB  - In medicine, there is a rapid development of a knowledge base. Medical
      professionals need to sustain and advance their competence to practice in
      response to these varieties. So, there is increased interest in self-directed
      learning methods. Study guides can make a major contribution to self-directed
      learning. This study was carried out to evaluate the effect of study guides on
      improving self-learning skills of medical students in the Iran University of
      Medical Sciences (IUMS). In this quasi-experimental study, 46 medical students
      were randomly assigned into two groups; the intervention group and the control
      group. Both groups participated in a diagnostic test at the beginning of the
      course (pre-test). The same test was taken at the end of the course (post-test).
      The intervention group was provided with study guides on thyroid disorders and
      diabetes. Meanwhile, they continued their routine clinical training. The control
      group was only involved in the conventional training program. Students in the
      intervention group were also asked to complete a designed questionnaire in regard
      to their attitude toward the study guides. At enrollment, there was no
      statistically significant difference between the two groups. The mean scores of
      the pre-test for the control group and the intervention group were 6.18 and 6.13
      respectively (P=0.9). In the post-test, the mean score of the students in the
      intervention group was considerably higher: 9.25 vs. 12 (P=0.002). The students
      in the intervention group found the study guides useful. The study guides were
      potentially effective in motivating self-learning in this group of medical
      students and had a remarkable effect on their final score. 

PMID- 25369015
TI  - Elephantiasis nostras verrucosa of lower limb: a case report.
AB  - Elephantiasis nostras verrucosa (ENV) is a rare condition in which
      hyperkeratosis, fibrosis and disfiguration of dermis occurs. It is caused mostly
      by non infectious diseases such as surgery, trauma, tumors, and venous
      obstructions. To our knowledge there is not any case report of ENV in Middle East
      region. In this patient, ENV caused by trauma and Patient presented with
      enlargement of right lower limb. 

PMID- 25369016
TI  - Indeterminate cell histiocytosis: report of a case.
AB  - Indeterminate cell histiocytosis is a very rare disorder of histiocytes
      proliferation. It has both Langerhans and non-Langerhans cell histiocytosis
      immunophenotypic features. We described a 45-year-old man with a 2 years history
      of multiple yellow-brown papules and a few red nodules on his trunk and
      extremities. No internal involvement was detected first and after 8 months. As
      his lesions were asymptomatic and sparse, he didn't receive any treatment. He
      will be followed at regular intervals. 

PMID- 25369017
TI  - Rectal lymphoma: report of a rare case and review of literature.
AB  - Colorectal lymphoma is an extremely rare disease, representing less than 0.5% of
      all primary colorectal neoplasms. The disease is usually diagnosed in the
      advanced stages because of its primary non-specific symptoms. The most common
      involved site is cecum followed by rectum and ascending colon. Diffuse large B
      cell lymphoma is a more frequent subtype. Although surgical resection is often
      technically feasible, optimal therapy for a colorectal lymphoma, especially
      rectal lymphoma, has not yet been identified. The authors describe a patient with
      the primary rectal lymphoma, high-grade features and complete response to
      chemotherapy. 

PMID- 25369018
TI  - Swimming by reciprocal motion at low Reynolds number.
AB  - Biological microorganisms swim with flagella and cilia that execute nonreciprocal
      motions for low Reynolds number (Re) propulsion in viscous fluids. This symmetry
      requirement is a consequence of Purcell's scallop theorem, which complicates the
      actuation scheme needed by microswimmers. However, most biomedically important
      fluids are non-Newtonian where the scallop theorem no longer holds. It should
      therefore be possible to realize a microswimmer that moves with reciprocal
      periodic body-shape changes in non-Newtonian fluids. Here we report a symmetric
      'micro-scallop', a single-hinge microswimmer that can propel in shear thickening
      and shear thinning (non-Newtonian) fluids by reciprocal motion at low Re.
      Excellent agreement between our measurements and both numerical and analytical
      theoretical predictions indicates that the net propulsion is caused by modulation
      of the fluid viscosity upon varying the shear rate. This reciprocal swimming
      mechanism opens new possibilities in designing biomedical microdevices that can
      propel by a simple actuation scheme in non-Newtonian biological fluids. 

PMID- 25369019
TI  - Chemically defined diet alters the protective properties of fructo
      oligosaccharides and isomalto-oligosaccharides in HLA-B27 transgenic rats.
AB  - Non-digestible oligosaccharides (NDO) were shown to reduce inflammation in
      experimental colitis, but it remains unclear whether microbiota changes mediate
      their colitis-modulating effects. This study assessed intestinal microbiota and
      intestinal inflammation after feeding chemically defined AIN-76A or rat chow
      diets, with or without supplementation with 8 g/kg body weight of fructo
      oligosaccharides (FOS) or isomalto-oligosaccharides (IMO). The study used HLA-B27
      transgenic rats, a validated model of inflammatory bowel disease (IBD), in a
      factorial design with 6 treatment groups. Intestinal inflammation and intestinal
      microbiota were analysed after 12 weeks of treatment. FOS and IMO reduced colitis
      in animals fed rat chow, but exhibited no anti-inflammatory effect when added to
      AIN-76A diets. Both NDO induced specific but divergent microbiota changes.
      Bifidobacteria and Enterobacteriaceae were stimulated by FOS, whereas copy
      numbers of Clostridium cluster IV were decreased. In addition, higher
      concentrations of total short-chain fatty acids (SCFA) were observed in cecal
      contents of rats on rat chow compared to the chemically defined diet. AIN-76A
      increased the relative proportions of propionate, iso-butyrate, valerate and iso
      valerate irrespective of the oligosaccharide treatment. The SCFA composition,
      particularly the relative concentration of iso-butyrate, valerate and iso
      valerate, was associated (P <= 0.004 and r >= 0.4) with increased colitis and IL
      1 beta concentration of the cecal mucosa. This study demonstrated that the
      protective effects of fibres on colitis development depend on the diet. Although
      diets modified specific cecal microbiota, our study indicates that these changes
      were not associated with colitis reduction. Intestinal inflammation was
      positively correlated to protein fermentation and negatively correlated with
      carbohydrate fermentation in the large intestine.

PMID- 25369020
TI  - Quantitative and qualitative assessment of Yttrium-90 PET/CT imaging.
AB  - Yttrium-90 is known to have a low positron emission decay of 32 ppm that may
      allow for personalized dosimetry of liver cancer therapy with (90)Y labeled
      microspheres. The aim of this work was to image and quantify (90)Y so that
      accurate predictions of the absorbed dose can be made. The measurements were
      performed within the QUEST study (University of Sydney, and Sirtex Medical,
      Australia). A NEMA IEC body phantom containing 6 fillable spheres (10-37 mm ?)
      was used to measure the 90Y distribution with a Biograph mCT PET/CT (Siemens,
      Erlangen, Germany) with time-of-flight (TOF) acquisition. A sphere to background
      ratio of 8:1, with a total (90)Y activity of 3 GBq was used. Measurements were
      performed for one week (0, 3, 5 and 7 d). he acquisition protocol consisted of 30
      min-2 bed positions and 120 min-single bed position. Images were reconstructed
      with 3D ordered subset expectation maximization (OSEM) and point spread function
      (PSF) for iteration numbers of 1-12 with 21 (TOF) and 24 (non-TOF) subsets and CT
      based attenuation and scatter correction. Convergence of algorithms and activity
      recovery was assessed based on regions-of-interest (ROI) analysis of the
      background (100 voxels), spheres (4 voxels) and the central low density insert
      (25 voxels). For the largest sphere, the recovery coefficient (RC) values for the
      30 min -2-bed position, 30 min-single bed and 120 min-single bed were 1.12 +/-
      0.20, 1.14 +/- 0.13, 0.97 +/- 0.07 respectively. For the smaller diameter
      spheres, the PSF algorithm with TOF and single bed acquisition provided a
      comparatively better activity recovery. Quantification of Y-90 using Biograph mCT
      PET/CT is possible with a reasonable accuracy, the limitations being the size of
      the lesion and the activity concentration present. At this stage, based on our
      study, it seems advantageous to use different protocols depending on the size of
      the lesion.

PMID- 25369021
TI  - From sedentary time to sedentary patterns: accelerometer data reduction decisions
      in youth.
AB  - AIM: This study aims to establish evidence-based accelerometer data reduction
      criteria to accurately assess total sedentary time and sedentary patterns in
      children. METHODS: Participants (n = 1057 European children; 9-13 yrs) were
      invited to wear an accelerometer for at least 6 consecutive days. We explored 1)
      non-wear time criteria; 2) minimum daily valid wear time; 3) differences between
      weekday and weekend day; and 4) minimum number of days of accelerometer wear by
      comparing the effects of commonly used data reduction decisions on total
      sedentary time, and duration and number of prolonged sedentary bouts. RESULTS:
      More than 60 consecutive minutes of zero counts was the optimal criterion for non
      wear time. Increasing the definition of a valid day from 8 to 10 hours wear time
      hardly influenced the sedentary outcomes, while the sample size of children with
      more than 4 valid days increased from 69 to 81%. On weekdays, children had on
      average 1 hour more wear time, 50 minutes more total sedentary time, 26 minutes
      more sedentary time accumulated in bouts, and 1 more sedentary bout. At least 6
      days of accelerometer data were needed to accurately represent weekly sedentary
      time and patterns. CONCLUSIONS: Based on our results we recommend 1) a minimum of
      60 minutes of consecutive zeros as the most realistic criterion for non-wear
      time; and 2) including at least six days with minimum eight valid hours to
      characterize children's usual total sedentary time and patterns, preferably
      including one weekend day.

PMID- 25369022
TI  - Lombards on the move--an integrative study of the migration period cemetery at
      Szolad, Hungary.
AB  - In 2005 to 2007 45 skeletons of adults and subadults were excavated at the
      Lombard period cemetery at Szolad (6th century A.D.), Hungary. Embedded into the
      well-recorded historical context, the article presents the results obtained by an
      integrative investigation including anthropological, molecular genetic and
      isotopic (delta(15)N, delta(13)C, (87)Sr/(86)Sr) analyses. Skeletal stress
      markers as well as traces of interpersonal violence were found to occur
      frequently. The mitochondrial DNA profiles revealed a heterogeneous spectrum of
      lineages that belong to the haplogroups H, U, J, HV, T2, I, and K, which are
      common in present-day Europe and in the Near East, while N1a and N1b are today
      quite rare. Evidence of possible direct maternal kinship was identified in only
      three pairs of individuals. According to enamel strontium isotope ratios, at
      least 31% of the individuals died at a location other than their birthplace
      and/or had moved during childhood. Based on the peculiar 87 Sr/86 Sr ratio
      distribution between females, males, and subadults in comparison to local
      vegetation and soil samples, we propose a three-phase model of group movement. An
      initial patrilocal group with narrower male but wider female Sr isotope
      distribution settled at Szolad, whilst the majority of subadults represented in
      the cemetery yielded a distinct Sr isotope signature. Owing to the virtual
      absence of Szolad-born adults in the cemetery, we may conclude that the
      settlement was abandoned after approx. one generation. Population heterogeneity
      is furthermore supported by the carbon and nitrogen isotope data. They indicate
      that a group of high-ranking men had access to larger shares of animal-derived
      food whilst a few individuals consumed remarkable amounts of millet. The inferred
      dynamics of the burial community are in agreement with hypotheses of a highly
      mobile lifestyle during the Migration Period and a short-term occupation of
      Pannonia by Lombard settlers as conveyed by written sources.

PMID- 25369023
TI  - Etiologic agents of central nervous system infections among febrile hospitalized
      patients in the country of Georgia.
AB  - OBJECTIVES: There is a large spectrum of viral, bacterial, fungal, and prion
      pathogens that cause central nervous system (CNS) infections. As such,
      identification of the etiological agent requires multiple laboratory tests and
      accurate diagnosis requires clinical and epidemiological information. This
      hospital-based study aimed to determine the main causes of acute meningitis and
      encephalitis and enhance laboratory capacity for CNS infection diagnosis.
      METHODS: Children and adults patients clinically diagnosed with meningitis or
      encephalitis were enrolled at four reference health centers. Cerebrospinal fluid
      (CSF) was collected for bacterial culture, and in-house and multiplex RT-PCR
      testing was conducted for herpes simplex virus (HSV) types 1 and 2, mumps virus,
      enterovirus, varicella zoster virus (VZV), Streptococcus pneumoniae, HiB and
      Neisseria meningitidis. RESULTS: Out of 140 enrolled patients, the mean age was
      23.9 years, and 58% were children. Bacterial or viral etiologies were determined
      in 51% of patients. Five Streptococcus pneumoniae cultures were isolated from
      CSF. Based on in-house PCR analysis, 25 patients were positive for S. pneumoniae,
      6 for N. meningitidis, and 1 for H. influenzae. Viral multiplex PCR identified
      infections with enterovirus (n = 26), VZV (n = 4), and HSV-1 (n = 2). No patient
      was positive for mumps or HSV-2. CONCLUSIONS: Study findings indicate that S.
      pneumoniae and enteroviruses are the main etiologies in this patient cohort. The
      utility of molecular diagnostics for pathogen identification combined with the
      knowledge provided by the investigation may improve health outcomes of CNS
      infection cases in Georgia.

PMID- 25369025
TI  - [Evidence-based decision-making: when it is worthwhile].
AB  - Every day health professionals have to make dozens of decisions regarding patient
      care and management. It is not easy to integrate scientific evidence in this
      process. The primary ability we need in order to achieve successful results is
      learning how to recognize the circumstances in which evidence arising from
      results of scientific trials may help. 

PMID- 25369024
TI  - Poly(A) RNAs including coding proteins RNAs occur in plant Cajal bodies.
AB  - The localisation of poly(A) RNA in plant cells containing either reticular
      (Allium cepa) or chromocentric (Lupinus luteus, Arabidopsis thaliana) nuclei was
      studied through in situ hybridisation. In both types of nuclei, the amount of
      poly(A) RNA was much greater in the nucleus than in the cytoplasm. In the nuclei,
      poly(A) RNA was present in structures resembling nuclear bodies. The molecular
      composition as well as the characteristic ultrastructure of the bodies containing
      poly(A) RNA demonstrated that they were Cajal bodies. We showed that some poly(A)
      RNAs in Cajal bodies code for proteins. However, examination of the localisation
      of active RNA polymerase II and in situ run-on transcription assays both
      demonstrated that CBs are not sites of transcription and that BrU-containing RNA
      accumulates in these structures long after synthesis. In addition, it was
      demonstrated that accumulation of poly(A) RNA occurs in the nuclei and CBs of
      hypoxia-treated cells. Our findings indicated that CBs may be involved in the
      later stages of poly(A) RNA metabolism, playing a role storage or retention. 

PMID- 25369026
TI  - Multiscale modelling and analysis of collective decision making in swarm
      robotics.
AB  - We present a unified approach to describing certain types of collective decision
      making in swarm robotics that bridges from a microscopic individual-based
      description to aggregate properties. Our approach encompasses robot swarm
      experiments, microscopic and probabilistic macroscopic-discrete simulations as
      well as an analytic mathematical model. Following up on previous work, we
      identify the symmetry parameter, a measure of the progress of the swarm towards a
      decision, as a fundamental integrated swarm property and formulate its time
      evolution as a continuous-time Markov process. Contrary to previous work, which
      justified this approach only empirically and a posteriori, we justify it from
      first principles and derive hard limits on the parameter regime in which it is
      applicable. 

PMID- 25369027
TI  - A novel technique of contrast-enhanced optical coherence tomography imaging in
      evaluation of clearance of lipids in human tears.
AB  - PURPOSE: The aim of this work was to gather preliminary data in different
      conditions of healthy eyes, aqueous tear deficient dry eyes, obstructive
      meibomian gland disease (MGD) and non-obvious obstructive MGD (NOMGD)
      individuals, using a new, contrast-enhanced optical coherence tomography (OCT)
      imaging method to evaluate the clearance of lipids in human tears. METHODS:
      Eighty-two adult patients presenting with complaints of ocular irritation were
      studied for abnormalities of the ocular surface and classified as healthy (n =
      21), aqueous tear deficient dry eyes (n = 20), obstructive MGD (n = 15) and NOMGD
      (n = 26) individuals. A lipid-based tracer, containing an oil-in-water emulsion,
      was used to obtain an enhanced OCT imaging of the lower tear meniscus. After
      instillation, a dramatic initial increase of reflectivity of the lower tear
      meniscus was detected by OCT, followed by a decay back to baseline values over
      time. Based on this finding, the clearance of lipids was measured in real-time by
      Fourier-domain anterior segment OCT. RESULTS: The differences in the clearance of
      lipids among the four groups as well as the correlations between symptom
      questionnaire score, standardized visual scale test, fluorescein break-up time,
      ocular surface fluorescein staining score, Schirmer I test scores were found to
      be statistically significant. The individual areas under the curve of the
      clearance of lipids calculated by the receiver operating characteristic curve
      technique ranged from 0.66 to 0.98, suggesting reliable sensitivity and
      specificity of lipid-enhanced OCT imaging. CONCLUSIONS: This new technique of
      contrast-enhanced OCT imaging of the tear film following lipid-based tracer
      instillation provides a measure of the clearance of lipids. The quantitative
      values found are in agreement with other methods of evaluation of the lacrimal
      system. An improvement of the clinician's ability in the diagnosis and
      understanding of abnormalities of the ocular surface may be achieved by this
      simple approach.

PMID- 25369028
TI  - Chronic Beryllium Disease: revealing the role of beryllium ion and small peptides
      binding to HLA-DP2.
AB  - Chronic Beryllium (Be) Disease (CBD) is a granulomatous disorder that
      predominantly affects the lung. The CBD is caused by Be exposure of individuals
      carrying the HLA-DP2 protein of the major histocompatibility complex class II
      (MHCII). While the involvement of Be in the development of CBD is obvious and the
      binding site and the sequence of Be and peptide binding were recently
      experimentally revealed [1], the interplay between induced conformational changes
      and the changes of the peptide binding affinity in presence of Be were not
      investigated. Here we carry out in silico modeling and predict the Be binding to
      be within the acidic pocket (Glu26, Glu68 and Glu69) present on the HLA-DP2
      protein in accordance with the experimental work [1]. In addition, the modeling
      indicates that the Be ion binds to the HLA-DP2 before the corresponding peptide
      is able to bind to it. Further analysis of the MD generated trajectories reveals
      that in the presence of the Be ion in the binding pocket of HLA-DP2, all the
      different types of peptides induce very similar conformational changes, but their
      binding affinities are quite different. Since these conformational changes are
      distinctly different from the changes caused by peptides normally found in the
      cell in the absence of Be, it can be speculated that CBD can be caused by any
      peptide in presence of Be ion. However, the affinities of peptides for Be loaded
      HLA-DP2 were found to depend of their amino acid composition and the peptides
      carrying acidic group at positions 4 and 7 are among the strongest binders. Thus,
      it is proposed that CBD is caused by the exposure of Be of an individual carrying
      the HLA-DP2*0201 allele and that the binding of Be to HLA-DP2 protein alters the
      conformational and ionization properties of HLA-DP2 such that the binding of a
      peptide triggers a wrong signaling cascade. 

PMID- 25369029
TI  - Suppression of proteoglycan-induced autoimmune arthritis by myeloid-derived
      suppressor cells generated in vitro from murine bone marrow.
AB  - BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are innate immune cells
      capable of suppressing T-cell responses. We previously reported the presence of
      MDSCs with a granulocytic phenotype in the synovial fluid (SF) of mice with
      proteoglycan (PG)-induced arthritis (PGIA), a T cell-dependent autoimmune model
      of rheumatoid arthritis (RA). However, the limited amount of SF-MDSCs precluded
      investigations into their therapeutic potential. The goals of this study were to
      develop an in vitro method for generating MDSCs similar to those found in SF and
      to reveal the therapeutic effect of such cells in PGIA. METHODS: Murine bone
      marrow (BM) cells were cultured for 3 days in the presence of granulocyte
      macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and
      granulocyte colony-stimulating factor (G-CSF). The phenotype of cultured cells
      was analyzed using flow cytometry, microscopy, and biochemical methods. The
      suppressor activity of BM-MDSCs was tested upon co-culture with activated T
      cells. To investigate the therapeutic potential of BM-MDSCs, the cells were
      injected into SCID mice at the early stage of adoptively transferred PGIA, and
      their effects on the clinical course of arthritis and PG-specific immune
      responses were determined. RESULTS: BM cells cultured in the presence of GM-CSF,
      IL-6, and G-CSF became enriched in MDSC-like cells that showed greater phenotypic
      heterogeneity than MDSCs present in SF. BM-MDSCs profoundly inhibited both
      antigen-specific and polyclonal T-cell proliferation primarily via production of
      nitric oxide. Injection of BM-MDSCs into mice with PGIA ameliorated arthritis and
      reduced PG-specific T-cell responses and serum antibody levels. CONCLUSIONS: Our
      in vitro enrichment strategy provides a SF-like, but controlled microenvironment
      for converting BM myeloid precursors into MDSCs that potently suppress both T
      cell responses and the progression of arthritis in a mouse model of RA. Our
      results also suggest that enrichment of BM in MDSCs could improve the therapeutic
      efficacy of BM transplantation in RA.

PMID- 25369030
TI  - Establishment of a humanized APL model via the transplantation of PML-RARA
      transduced human common myeloid progenitors into immunodeficient mice.
AB  - Recent advances in cancer biology have revealed that many malignancies possess a
      hierarchal system, and leukemic stem cells (LSC) or leukemia-initiating cells
      (LIC) appear to be obligatory for disease progression. Acute promyelocytic
      leukemia (APL), a subtype of acute myeloid leukemia characterized by the
      formation of a PML-RARalpha fusion protein, leads to the accumulation of abnormal
      promyelocytes. In order to understand the precise mechanisms involved in human
      APL leukemogenesis, we established a humanized in vivo APL model involving
      retroviral transduction of PML-RARA into CD34(+) hematopoietic cells from human
      cord blood and transplantation of these cells into immunodeficient mice. The
      leukemia well recapitulated human APL, consisting of leukemic cells with abundant
      azurophilic abnormal granules in the cytoplasm, which expressed CD13, CD33 and
      CD117, but not HLA-DR and CD34, were clustered in the same category as human APL
      samples in the gene expression analysis, and demonstrated sensitivity to ATRA. As
      seen in human APL, the induced APL cells showed a low transplantation efficiency
      in the secondary recipients, which was also exhibited in the transplantations
      that were carried out using the sorted CD34- fraction. In order to analyze the
      mechanisms underlying APL initiation and development, fractionated human cord
      blood was transduced with PML-RARA. Common myeloid progenitors (CMP) from
      CD34(+)/CD38(+) cells developed APL. These findings demonstrate that CMP are a
      target fraction for PML-RARA in APL, whereas the resultant CD34(-) APL cells may
      share the ability to maintain the tumor.

PMID- 25369031
TI  - Protection of armadillo/beta-Catenin by armless, a novel positive regulator of
      wingless signaling.
AB  - The Wingless (Wg/Wnt) signaling pathway is essential for metazoan development,
      where it is central to tissue growth and cellular differentiation. Deregulated Wg
      pathway activation underlies severe developmental abnormalities, as well as
      carcinogenesis. Armadillo/beta-Catenin plays a key role in the Wg transduction
      cascade; its cytoplasmic and nuclear levels directly determine the output
      activity of Wg signaling and are thus tightly controlled. In all current models,
      once Arm is targeted for degradation by the Arm/beta-Catenin destruction complex,
      its fate is viewed as set. We identified a novel Wg/Wnt pathway component,
      Armless (Als), which is required for Wg target gene expression in a cell
      autonomous manner. We found by genetic and biochemical analyses that Als
      functions downstream of the destruction complex, at the level of the
      SCF/Slimb/betaTRCP E3 Ub ligase. In the absence of Als, Arm levels are severely
      reduced. We show by biochemical and in vivo studies that Als interacts directly
      with Ter94, an AAA ATPase known to associate with E3 ligases and to drive protein
      turnover. We suggest that Als antagonizes Ter94's positive effect on E3 ligase
      function and propose that Als promotes Wg signaling by rescuing Arm from
      proteolytic degradation, spotlighting an unexpected step where the Wg pathway
      signal is modulated. 

PMID- 25369032
TI  - How difficult is inference of mammalian causal gene regulatory networks?
AB  - Gene regulatory networks (GRNs) play a central role in systems biology,
      especially in the study of mammalian organ development. One key question remains
      largely unanswered: Is it possible to infer mammalian causal GRNs using
      observable gene co-expression patterns alone? We assembled two mouse GRN datasets
      (embryonic tooth and heart) and matching microarray gene expression profiles to
      systematically investigate the difficulties of mammalian causal GRN inference.
      The GRNs were assembled based on > 2,000 pieces of experimental genetic
      perturbation evidence from manually reading > 150 primary research articles. Each
      piece of perturbation evidence records the qualitative change of the expression
      of one gene following knock-down or over-expression of another gene. Our data
      have thorough annotation of tissue types and embryonic stages, as well as the
      type of regulation (activation, inhibition and no effect), which uniquely allows
      us to estimate both sensitivity and specificity of the inference of tissue
      specific causal GRN edges. Using these unprecedented datasets, we found that gene
      co-expression does not reliably distinguish true positive from false positive
      interactions, making inference of GRN in mammalian development very difficult.
      Nonetheless, if we have expression profiling data from genetic or molecular
      perturbation experiments, such as gene knock-out or signalling stimulation, it is
      possible to use the set of differentially expressed genes to recover causal
      regulatory relationships with good sensitivity and specificity. Our result
      supports the importance of using perturbation experimental data in causal network
      reconstruction. Furthermore, we showed that causal gene regulatory relationship
      can be highly cell type or developmental stage specific, suggesting the
      importance of employing expression profiles from homogeneous cell populations.
      This study provides essential datasets and empirical evidence to guide the
      development of new GRN inference methods for mammalian organ development.

PMID- 25369034
TI  - Detection of rotavirus using padlock probes and rolling circle amplification.
AB  - Rotavirus infections are one of the most common reasons for hospitalizations due
      to gastrointestinal diseases. Rotavirus is often diagnosed by latex agglutination
      assay, chromatography immunoassay, or by electron microscopy, which are all quite
      insensitive. Reverse transcription polymerase chain reaction, on the other hand,
      is very sensitive to variations at the genomic level. We developed a novel assay
      based on a set of 58 different padlock probes with a detection limit of 1,000
      copies. Twenty-two patient samples were analyzed and the assay showed high
      concordance with a PCR-based assay. In summary, we present a new assay for
      sensitive and variation tolerant detection of rotavirus. 

PMID- 25369033
TI  - Methylation affects transposition and splicing of a large CACTA transposon from a
      MYB transcription factor regulating anthocyanin synthase genes in soybean seed
      coats.
AB  - We determined the molecular basis of three soybean lines that vary in seed coat
      color at the R locus which is thought to encode a MYB transcription factor. RM55
      r(m) is homozygous for a mutable allele (r(m)) that specifies black and brown
      striped seeds; RM30-R* is a stable black revertant isoline derived from the
      mutable line; and RM38-r has brown seed coats due to a recessive r allele shown
      to translate a truncated MYB protein. Using long range PCR, 454 sequencing of
      amplicons, and whole genome re-sequencing, we determined that the variegated RM55
      r(m) line had a 13 kb CACTA subfamily transposon insertion (designated TgmR*) at
      a position 110 bp from the beginning of Intron2 of the R locus, Glyma09g36983.
      Although the MYB encoded by R was expressed at only very low levels in older seed
      coats of the black revertant RM30-R* line, it upregulated expression of
      anthocyanidin synthase genes (ANS2, ANS3) to promote the synthesis of
      anthocyanins. Surprisingly, the RM30-R* revertant also carried the 13 kb TgmR*
      insertion in Intron2. Using RNA-Seq, we showed that intron splicing was accurate,
      albeit at lower levels, despite the presence of the 13 kb TgmR* element. As
      determined by whole genome methylation sequencing, we demonstrate that the TgmR*
      sequence was relatively more methylated in RM30-R* than in the mutable RM55-r(m)
      progenitor line. The stabilized and more methylated RM30-R* revertant line
      apparently lacks effective binding of a transposae to its subterminal repeats,
      thus allowing intron splicing to proceed resulting in sufficient MYB protein to
      stimulate anthocyanin production and thus black seed coats. In this regard, the
      TgmR* element in soybean resembles McClintock's Spm-suppressible and change-of
      state alleles of maize. This comparison explains the opposite effects of the
      TgmR* element on intron splicing of the MYB gene in which it resides depending on
      the methylation state of the element.

PMID- 25369035
TI  - Three-dimensional plasmonic stereoscopic prints in full colour.
AB  - Metal nanostructures can be designed to scatter different colours depending on
      the polarization of the incident light. Such spectral control is attractive for
      applications such as high-density optical storage, but challenges remain in
      creating microprints with a single-layer architecture that simultaneously enables
      full-spectral and polarization control of the scattered light. Here we
      demonstrate independently tunable biaxial colour pixels composed of isolated
      nanoellipses or nanosquare dimers that can exhibit a full range of colours in
      reflection mode with linear polarization dependence. Effective polarization
      sensitive full-colour prints are realized. With this, we encoded two colour
      images within the same area and further use this to achieve depth perception by
      realizing three-dimensional stereoscopic colour microprint. Coupled with the low
      cost and durability of aluminium as the functional material in our pixel design,
      such polarization-sensitive encoding can realize a wide spectrum of applications
      in colour displays, data storage and anti-counterfeiting technologies. 

PMID- 25369036
TI  - A novel fungal hyperparasite of Puccinia striiformis f. sp. tritici, the causal
      agent of wheat stripe rust.
AB  - Puccinia striiformis f. sp. tritici (Pst), the causal fungus of wheat stripe
      rust, was previously reported to be infected by Lecanicillium lecanii,
      Microdochium nivale and Typhula idahoensis. Here, we report a novel hyperparasite
      on Pst. This hyperparasitic fungus was identified as Cladosporium cladosporioides
      (Fresen.) GA de Vries based on morphological characteristics observed by light
      and scanning electron microscopy together with molecular data. The hyperparasite
      reduced the production and viability of urediniospores and, therefore, could
      potentially be used for biological control of wheat stripe rust. 

PMID- 25369038
TI  - Liver stiffness measurement among patients with chronic hepatitis B and C:
      results from a 5-year prospective study.
AB  - Liver stiffness measurement (LSM) is widely used to evaluate liver fibrosis, but
      longitudinal studies are rare. The current study was aimed to monitor LSM during
      follow-up, and to evaluate the association of LSM data with mortality and liver
      related outcomes. We included all patients with chronic viral hepatitis and valid
      LSM using Fibroscan. Information about liver biopsy, antiviral treatment, and
      clinical outcome was obtained from medical records and national registers. The
      study included 845 patients: 597 (71%) with hepatitis C virus (HCV), 235 (28%)
      with hepatitis B virus (HBV) and 13 (2%) with dual infection. The initial LSM
      distribution (<7/7-9.9/10-16.9/>= 17 kPa) was 58%/16%/14%/12%. Among patients
      with initial LSM values of 7-9.9 kPa, 60% of HCV patients and 83% of HBV patients
      showed LSM values of <7 kPa at the latest follow-up. Progression rates (defined
      as >20% and >2 kPa increase, with one measure >7 kPa) were 3.4/100 person years
      (PY) for HCV and 1.5/100 PY for HBV infected patients. Patients with LSM values
      of >= 17 kPa had the same liver-related complication incidence as patients with
      biopsy-proven cirrhosis (11.1 versus 12.1/100 PY). Thirteen liver-related deaths
      occurred among HCV patients (0.6/100 PY), but none among HBV patients. Among
      patients who died of liver-related causes, all but one had baseline LSM values of
      >= 17 kPa. Overall, patients with LSM values <17 kPa were not associated with
      adverse outcomes. In contrast, LSM values >= 17 kPa were associated with
      significant risk of liver-related problems. The results of the current study
      suggest that clinical decisions should not be taken based on a single LSM
      measurement.

PMID- 25369039
TI  - The effect of time postexposure and sex on the horizontal transmission of
      Metarhizium brunneum conidia between Asian longhorned beetle (Coleoptera:
      Cerambycidae) mates.
AB  - A study using Metarhizium brunneum Petch fungal bands designed to improve
      delivery of conidia to adult Asian longhorned beetles, Anoplophora glabripennis
      (Motschulsky), was conducted to determine how a time delay between exposure to
      infective conidia and pairing of male and female beetles would affect the ability
      to successfully transfer lethal doses of conidia to a mate. We measured conidial
      load at the time of mate pairing (0, 4, 24, 48 h postexposure) and assessed its
      effect on beetle mortality. Conidial load per beetle decreased across the four
      sampling times, and there was no effect of beetle sex on conidial load. At all
      time periods postexposure, beetles that climbed across fungal bands carried
      enough conidia that at least some of their indirectly exposed mates died of
      mycosis. For indirectly exposed beetles, mortality decreased significantly as the
      time delay increased from 0 to 48 h, and this was independent of beetle sex.
      Median survival time was only 11.5 d for females indirectly exposed immediately
      after their mate had been exposed, but >3 wk when there was a 48-h delay before
      pairing. Generally, beetles exposed directly to fungal bands died faster than
      their indirectly exposed mates. In contrast to the pattern seen for indirectly
      exposed beetles, beetles exposed directly to fungal bands showed no change in
      survival times with a delay between exposure and pairing. Median survival times
      of exposed females and males were generally similar, at 10.5-12.5 d. 

PMID- 25369041
TI  - [Hypertension: self-monitoring even in high cardiovascular risk? - Hypertensive
      patients benefit from self-monitoring].

PMID- 25369040
TI  - Age-related cataract, cataract surgery and subsequent mortality: a systematic
      review and meta-analysis.
AB  - PURPOSE: Changes in lens may reflect the status of systemic health of human
      beings but the supporting evidences are not well summarized yet. We aimed to
      determine the relationship of age-related cataract, cataract surgery and long
      term mortality by pooling the results of published population-based studies.
      METHODS: We searched PubMed and Embase from their inception till March, 2014 for
      population-based studies reporting the associations of any subtypes of age
      related cataract, cataract surgery with all-cause mortality. We pooled the effect
      estimates (hazards ratios [HRs]) under a random effects model. RESULTS: Totally,
      we identified 10 unique population-based studies including 39,659 individuals at
      baseline reporting the associations of any subtypes of cataract with all-cause
      mortality from 6 countries. The presence of any cataract including cataract
      surgery was significantly associated with a higher risk of death (pooled HR:
      1.43, 95% CI, 1.21, 2.02; P<0.001; I(2) = 64.2%). In the meta-analysis of 9 study
      findings, adults with nuclear cataract were at higher risks of mortality (pooled
      HR: 1.55, 95% CI, 1.17, 2.05; P = 0.002; I(2) = 89.2%). In the meta-analysis of 8
      study findings, cortical cataract was associated with higher risks of mortality
      (pooled HR: 1.26, 95% CI, 1.12, 1.42; P<0.001, I(2) = 29.7%). In the meta
      analysis of 6 study findings, PSC cataract was associated with higher risks of
      mortality (pooled HR: 1.37, 95% CI, 1.04, 1.80; P = 0.03; I(2) = 67.3%). The
      association between cataract surgery and mortality was marginally non-significant
      by pooling 8 study findings (pooled HR: 1.27, 95% CI, 0.97, 1.66; P = 0.08; I(2)=
      76.6%). CONCLUSIONS: All subtypes of age-related cataract were associated with an
      increased mortality with nuclear cataract having the strongest association among
      the 3 cataract subtypes. However, cataract surgery was not significantly related
      to mortality. These findings indicated that changes in lens may serve as markers
      for ageing and systemic health in general population.

PMID- 25369042
TI  - [Gender-specific differences in hemodynamically stable patients with acute
      pulmonary embolism].
AB  - BACKGROUND AND AIM: Pulmonary embolism (PE) is potentially life-threatening. Aim
      of this study was to identify genderspecific differences in acute PE and in risk
      stratification of hemodynamically stable PE patients. METHODS: We analysed
      retrospectively the data of 129 patients with PE (59.7% women) and compared
      female and male patients regarding clinical, laboratory and technical parameters.
      ROC curve and Youden Index were calculated to analyse cardiac troponin I (cTnI)
      for predicting of right ventricular dysfunction (RVD) and D-Dimer for predicting
      submassive PE. RESULTS: 129 patients were included in this study. Female patients
      were older (median 73.0 [25th percentile: 65.0/75th percentile: 81.0] vs. 65.5
      [55.2/76.6] years, p = 0.0095) and had more frequent submassive PE (82.7% vs.
      64.0%, p = 0.03) with higher systolic pulmonary artery pressure (38.00 +/- 18.23
      vs. 27.87 +/- 17.32 mmHg, p = 0.0018). Multivariable regression analysis showed a
      strong association between cTnI and RVD (OR, 2.84; 95%CI: 1.52-5.32, p = 0.0011).
      Association between cTnI and RVD was stronger in male PE patients (OR, 27.67;
      95%CI: 3.28-233.31, p = 0.0023) than in female (OR, 1.52; 95%CI: 0.79-2.93, p =
      0.21). Area under the curve (AUC) for efficiency of cTnI predicting RVD was
      higher in male patients (0.92 vs. 0.69). AUC for efficiency of D-Dimer predicting
      submassive PE was similar in both genders (0.65 vs. 0.62). Genderspecific cTnI
      cut-off values indicating for RVD, were similar in male and female (> 0.00 vs. >
      0.01 ng/ml). D-Dimer values above 1.08 mg/dl in male and 1.41 mg/dl in female
      indicated for submassive PE. CONCLUSION: Normotensive female PE patients are in
      mean older and have more frequently submassive PE stadium. cTnI is associated
      with RVD. cTnI as risk stratification marker for predicting RVD is more effective
      in male.

PMID- 25369043
TI  - [Quality of life of young adults after a growth hormone therapy with childhood
      onset].
AB  - INTRODUCTION: Little is known about the health-related quality of life of young
      adults with childhood onset idiopathic growth hormone deficiency or
      neurosecretory dysfunction of growth hormone secretion, who have been treated
      with recombinant human growth hormone (GH). METHODS: Patients were diagnosed and
      treated with human growth hormone at the University Children's Hospital in
      Erlangen (n=85). The data of both groups were merged for analysis, because no
      difference between idiopathic growth hormone deficiency and neurosecretory
      dysfunction of growth hormone secretion in auxological. Data were found. Health
      related quality of life was cross- sectionally assessed after the end of growth
      hormone therapy with the Short Form-36 Health Survey and the Nottingham Health
      Profiles for which population based norm data are available. RESULTS: At the time
      of the survey, the patients (53 m, 32 f) were 23.5 +/- 4.6 years old. At start of
      GH therapy, age was 10.5 +/- 2.8 and at the end 16.3 +/- 1,4 years. At start,
      height SDS was -3.20 +/- 1.06. GH dose was 0,026 +/- 0,012 mg/kg/d (daily s. c.
      injections). The increase in height SDS after the end of GH therapy was 1.69 +/-
      1.22.  Compared to the reference population, patients reported significantly
      lower scores on the scales energy level, vitality, social functioning, indicating
      a greater social isolation, a stronger emotional reaction, an increased loss of
      mobility and a worse psychological state. CONCLUSION: Young adults report
      specific impairments after completion of GH therapy.

PMID- 25369044
TI  - [35-year-old patient with unclear dermatological finding].

PMID- 25369045
TI  - [Sensory aphasia during therapy with metronidazole--an important differential
      diagnosis of acute cerebral ischemia].
AB  - HISTORY AND ADMISSION FINDINGS: A 74-year old man was admitted after
      neurosurgical treatment of a lumbar vertebral fracture. He had a slight paresis
      of the right leg in combination with bladder dysfunction. INVESTIGATIONS: There
      were signs of a postoperative anemia (hemoglobin 10.4 mg/dl) and mildly elevated
      infection parameters (CRP 2 mg/dl). Routine ECG and chest X-ray were normal.
      TREATMENT AND COURSE: Physical training was initiated, but diarrhea occurred 2
      days after admission. As the patient had received antibiotics after the
      operation, a treatment with metronidazole was initiated under the suspicion of
      diarrhoea induced by clostridium difficile. At day 6 of treatment a hypertensive
      crisis (blood pressure 230/120 mmHg) developed, followed by sensory aphasia.
      Despite treatment at the stroke unit and blood pressure regulation, the clinical
      signs of aphasia persisted. MRI could not detect an acute cerebral infarction.
      After discontinuation of metronidazole complete reconstitution occurred within 72
      h. CONCLUSION: Metronidazole should be taken into account as cause of severe
      neurological side effects including ischemia-like syndromes like aphasia.

PMID- 25369046
TI  - [Possibilities of duplex-sonography for the examination of intrarenal bloodflow].

PMID- 25369047
TI  - [Medical apps in clinical use: mobile success].

PMID- 25369048
TI  - [Integrated psychooncology: implementation of psychooncological health care at
      the Center for Integrated Oncology Cologne - Bonn].

PMID- 25369050
TI  - Microwave-assisted preparation of 4-amino-3-cyano-5-methoxycarbonyl-N
      arylpyrazoles as building blocks for the diversity-oriented synthesis of pyrazole
      based polycyclic scaffolds.
AB  - The synthesis of 4-amino-3-cyano-N-arylpyrazoles A based on a Thorpe-Ziegler
      cyclization as the key step has been achieved using microwave activation. Via a
      new diversity-oriented synthetic pathway, these highly functionalized building
      blocks allowed the access to various heteroaromatic scaffolds such as pyrazolo
      pyridines B, pyrazolo-pyrimidines C and pyrazolo-oxadiazoles D. Interestingly,
      these platforms contain three to four reactive sites that could be used for post
      functionalization in order to further increase the molecular diversity. 

PMID- 25369049
TI  - Inhibition of NKCC1 attenuated hippocampal LTP formation and inhibitory avoidance
      in rat.
AB  - The loop diuretic bumetanide (Bumex) is thought to have antiepileptic properties
      via modulate GABAA mediated signaling through their antagonism of cation-chloride
      cotransporters. Given that loop diuretics may act as antiepileptic drugs that
      modulate GABAergic signaling, we sought to investigate whether they also affect
      hippocampal function. The current study was performed to evaluate the possible
      role of NKCC1 on the hippocampal function. Brain slice extracellular recording,
      inhibitory avoidance, and western blot were applied in this study. Results showed
      that hippocampal Long-term potentiation was attenuated by suprafusion of NKCC1
      inhibitor bumetanide, in a dose dependent manner. Sequent experiment result
      showed that Intravenous injection of bumetanide (15.2 mg/kg) 30 min prior to the
      training session blocked inhibitory avoidance learning significantly. Subsequent
      control experiment's results excluded the possible non-specific effect of
      bumetanide on avoidance learning. We also found the phosphorylation of
      hippocampal MAPK was attenuated after bumetanide administration. These results
      suggested that hippocampal NKCC1 may via MAPK signaling cascade to possess its
      function. 

PMID- 25369051
TI  - Phospho-aspirin-2 (MDC-22) inhibits estrogen receptor positive breast cancer
      growth both in vitro and in vivo by a redox-dependent effect.
AB  - Phospho-aspirin (PA-2) is a novel aspirin derivative that exhibits promising
      anticancer properties and is considerably safer than conventional aspirin. In
      this study, we investigated the chemotherapeutic efficacy of PA-2 in preclinical
      models of estrogen receptor positive (ER+) breast cancer and elucidated its
      mechanism of action. PA-2 inhibited the growth of ER+ cells more potently than
      aspirin in vitro, and exerted a triple cytokinetic effect that includes induction
      of apoptosis and cell cycle arrest as well as the inhibition of cell
      proliferation. PA-2 is highly efficacious in vivo, as treatment of established
      MCF7 xenografts with PA-2 induced tumor stasis (98.2% inhibition, p<0.01). PA-2
      triggered the activation of p53-dependent apoptosis via two distinct mechanisms:
      1) acetylation of p53 (at K373), which disrupts its interaction with its
      transcription repressor MDM2, and 2) translocation of p53 to the mitochondria
      leading to the dissipation of mitochondrial transmembrane potential
      (DeltaPsi(m)). Consistent with these observations, both the RNAi-mediated
      knockdown of p53 and forced deactylation via HDAC1 over-expression attenuated the
      anticancer effect of PA-2 in MCF7 cells. An upstream mediator of the signaling
      effects of PA-2 is RONS. PA-2 induced oxidative stress in vitro and in mice
      bearing MCF7 xenografts; its induction effect appears to be tumor-specific.
      Crucially, administration of N-acetylcysteine, a ROS scavenger, abrogated the
      effect of PA-2 on p53 acetylation and mitochondria translocation, thus
      identifying RONS as proximal molecules mediating the anticancer effect of PA-2.
      In summary, our findings demonstrate that PA-2 is a promising antineoplastic
      compound against ER+ breast cancer, warranting further evaluation as an
      anticancer agent.

PMID- 25369052
TI  - Discovering main genetic interactions with LABNet LAsso-based network inference.
AB  - Genome-wide association studies can potentially unravel the mechanisms behind
      complex traits and common genetic diseases. Despite the valuable results produced
      thus far, many questions remain unanswered. For instance, which specific genetic
      compounds are linked to the risk of the disease under investigation; what
      biological mechanism do they act through; or how do they interact with
      environmental and other external factors? The driving force of computational
      biology is the constantly growing amount of big data generated by high-throughput
      technologies. A practical framework that can deal with this abundance of
      information and that consent to discovering genetic associations and interactions
      is provided by means of networks. Unfortunately, high dimensionality, the
      presence of noise and the geometry of data can make the aforementioned problem
      extremely challenging. We propose a penalised linear regression approach that can
      deal with the aforementioned issues that affect genetic data. We analyse the gene
      expression profiles of individuals with a common trait to infer the network
      structure of interactions among genes. The permutation-based approach leads to
      more stable and reliable networks inferred from synthetic microarray data. We
      show that a higher number of permutations determines the number of predicted
      edges, improves the overall sensitivity and controls the number of false
      positives. 

PMID- 25369054
TI  - Fungicide effects on fungal community composition in the wheat phyllosphere.
AB  - The fungicides used to control diseases in cereal production can have adverse
      effects on non-target fungi, with possible consequences for plant health and
      productivity. This study examined fungicide effects on fungal communities on
      winter wheat leaves in two areas of Sweden. High-throughput 454 sequencing of the
      fungal ITS2 region yielded 235 operational taxonomic units (OTUs) at the species
      level from the 18 fields studied. It was found that commonly used fungicides had
      moderate but significant effect on fungal community composition in the wheat
      phyllosphere. The relative abundance of several saprotrophs was altered by
      fungicide use, while the effect on common wheat pathogens was mixed. The fungal
      community on wheat leaves consisted mainly of basidiomycete yeasts, saprotrophic
      ascomycetes and plant pathogens. A core set of six fungal OTUs representing
      saprotrophic species was identified. These were present across all fields,
      although overall the difference in OTU richness was large between the two areas
      studied. 

PMID- 25369053
TI  - Hesperidin produces cardioprotective activity via PPAR-gamma pathway in ischemic
      heart disease model in diabetic rats.
AB  - The present study investigated the effect of hesperidin, a natural flavonoid, in
      cardiac ischemia and reperfusion (I/R) injury in diabetic rats. Male Wistar rats
      with diabetes were divided into five groups and were orally administered saline
      once daily (IR-sham and IR-control), Hesperidin (100 mg/kg/day; IR-Hesperidin),
      GW9962 (PPAR-gamma receptor antagonist), or combination of both for 14 days. On
      the 15th day, in the IR-control and IR-treatment groups, rats were subjected to
      left anterior descending (LAD) coronary artery occlusion for 45 minutes followed
      by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were
      sacrificed; hearts were isolated for biochemical, histopathological,
      ultrastructural and immunohistochemistry. In the IR-control group, significant
      ventricular dysfunctions were observed along with enhanced expression of pro
      apoptotic protein Bax. A decline in cardiac injury markers lactate dehydrogenase
      activity, CK-MB and increased content of thiobarbituric acid reactive substances,
      a marker of lipid peroxidation, and TNF-alpha were observed. Hesperidin
      pretreatment significantly improved mean arterial pressure, reduced left
      ventricular end-diastolic pressure, and improved both inotropic and lusitropic
      function of the heart (+LVdP/dt and -LVdP/dt) as compared to IR-control.
      Furthermore, hesperidin treatment significantly decreased the level of
      thiobarbituric acid reactive substances and reversed the activity of lactate
      dehydrogenase towards normal value. Hesperidin showed anti-apoptotic effects by
      upregulating Bcl-2 protein and decreasing Bax protein expression. Additionally,
      histopathological and ultrastructural studies reconfirmed the protective action
      of hesperidin. On the other hand, GW9662, selective PPAR-gamma receptor
      antagonist, produced opposite effects and attenuated the hesperidin induced
      improvements. The study for the first time evidence the involvement of PPAR-gamma
      pathway in the cardioprotective activity of hesperidin in I/R model in rats. 

PMID- 25369056
TI  - Cationic azacryptands as selective three-way DNA junction binding agents.
AB  - DNA damaging agents are among the most powerful anticancer drugs currently in
      clinical use. As an alternative to irreversible nucleobase damage and DNA strand
      breaks, the non-covalent stabilization of unusual, non-B DNA structures is
      currently emerging as a promising way to cause DNA damage with a high level of
      specificity. One of such non-B DNA structures is the three-way DNA junction: this
      Y-shaped multi-stranded architecture may act as an impediment to many DNA
      transactions, being therefore regarded as an invaluable target to create genomic
      defects that are improperly dealt with by cancer cells only. Herein, we report on
      a series of cationic azacryptands that make excellent candidates for assessing
      and harnessing the actual therapeutic potential of three-way DNA junction
      interacting compounds. 

PMID- 25369055
TI  - Role of alpha-globin H helix in the building of tetrameric human hemoglobin:
      interaction with alpha-hemoglobin stabilizing protein (AHSP) and heme molecule.
AB  - Alpha-Hemoglobin Stabilizing Protein (AHSP) binds to alpha-hemoglobin (alpha-Hb)
      or alpha-globin and maintains it in a soluble state until its association with
      the beta-Hb chain partner to form Hb tetramers. AHSP specifically recognizes the
      G and H helices of alpha-Hb. To investigate the degree of interaction of the
      various regions of the alpha-globin H helix with AHSP, this interface was studied
      by stepwise elimination of regions of the alpha-globin H helix: five truncated
      alpha-Hbs alpha-Hb1-138, alpha-Hb1-134, alpha-Hb1-126, alpha-Hb1-123, alpha-Hb1
      117 were co-expressed with AHSP as two glutathione-S-transferase (GST) fusion
      proteins. SDS-PAGE and Western Blot analysis revealed that the level of
      expression of each truncated alpha-Hb was similar to that of the wild type alpha
      Hb except the shortest protein alpha-Hb1-117 which displayed a decreased
      expression. While truncated GST-alpha-Hb1-138 and GST-alpha-Hb1-134 were normally
      soluble; the shorter globins GST-alpha-Hb1-126 and GST-alpha-Hb1-117 were
      obtained in very low quantities, and the truncated GST-alpha-Hb1-123 provided the
      least material. Absorbance and fluorescence studies of complexes showed that the
      truncated alpha-Hb1-134 and shorter forms led to modified absorption spectra
      together with an increased fluorescence emission. This attests that shortening
      the H helix leads to a lower affinity of the alpha-globin for the heme. Upon
      addition of beta-Hb, the increase in fluorescence indicates the replacement of
      AHSP by beta-Hb. The CO binding kinetics of different truncated AHSPWT/alpha-Hb
      complexes showed that these Hbs were not functionally normal in terms of the
      allosteric transition. The N-terminal part of the H helix is primordial for
      interaction with AHSP and C-terminal part for interaction with heme, both
      features being required for stability of alpha-globin chain. 

PMID- 25369057
TI  - Validation of a consensus method for identifying delirium from hospital records.
AB  - BACKGROUND: Delirium is increasingly considered to be an important determinant of
      trajectories of cognitive decline. Therefore, analyses of existing cohort studies
      measuring cognitive outcomes could benefit from methods to ascertain a
      retrospective delirium diagnosis. This study aimed to develop and validate such a
      method for delirium detection using routine medical records in UK and Ireland.
      METHODS: A point prevalence study of delirium provided the reference-standard
      ratings for delirium diagnosis. Blinded to study results, clinical vignettes were
      compiled from participants' medical records in a standardised manner, describing
      any relevant delirium symptoms recorded in the whole case record for the period
      leading up to case-ascertainment. An expert panel rated each vignette as
      unlikely, possible, or probable delirium and disagreements were resolved by
      consensus. RESULTS: From 95 case records, 424 vignettes were abstracted by 5
      trained clinicians. There were 29 delirium cases according to the reference
      standard. Median age of subjects was 76.6 years (interquartile range 54.6 to
      82.5). Against the original study DSM-IV diagnosis, the chart abstraction method
      gave a positive likelihood ratio (LR) of 7.8 (95% CI 5.7-12.0) and the negative
      LR of 0.45 (95% CI 0.40-0.47) for probable delirium (sensitivity 0.58 (95% CI
      0.53-0.62); specificity 0.93 (95% CI 0.90-0.95); AUC 0.86 (95% CI 0.82-0.89)).
      The method diagnosed possible delirium with positive LR 3.5 (95% CI 2.9-4.3) and
      negative LR 0.15 (95% CI 0.11-0.21) (sensitivity 0.89 (95% CI 0.85-0.91);
      specificity 0.75 (95% CI 0.71-0.79); AUC 0.86 (95% CI 0.80-0.89)). CONCLUSIONS:
      This chart abstraction method can retrospectively diagnose delirium in
      hospitalised patients with good accuracy. This has potential for retrospectively
      identifying delirium in cohort studies where routine medical records are
      available. This example of record linkage between hospitalisations and
      epidemiological data may lead to further insights into the inter-relationship
      between acute illness, as an exposure, for a range of chronic health outcomes.

PMID- 25369059
TI  - [Clinical experience with a C-section surgical technique in patients with morbid
      obesity: a case series].
AB  - Obesity is a public health challenge that has crossed into the area of
      reproductive health. An obese pregnant woman has multiple complications before,
      during, and after pregnancy. Likewise, cesarean section is more difficult and has
      slower recovery times in this group of patients. This paper proposes a surgical
      technique adapted to the morbidly obese pregnant patient that aims to reduce
      cesarean section complications. 

PMID- 25369058
TI  - IRE1 phosphatase PP2Ce regulates adaptive ER stress response in the postpartum
      mammary gland.
AB  - We recently reported that the PPM1l gene encodes an endoplasmic reticulum (ER)
      membrane targeted protein phosphatase (named PP2Ce) with highly specific activity
      towards Inositol-requiring protein-1 (IRE1) and regulates the functional outcome
      of ER stress. In the present report, we found that the PP2Ce protein is highly
      expressed in lactating epithelium of the mammary gland. Loss of PP2Ce in vivo
      impairs physiological unfolded protein response (UPR) and induces stress kinase
      activation, resulting in loss of milk production and induction of epithelial
      apoptosis in the lactating mammary gland. This study provides the first in vivo
      evidence that PP2Ce is an essential regulator of normal lactation, possibly
      involving IRE1 signaling and ER stress regulation in mammary epithelium. 

PMID- 25369060
TI  - How to live with the enemy: understanding tolerance to parasites.
AB  - How do we defend ourselves against pathogenic microbes and other parasites
      infecting us? Research on defence against parasites has traditionally focused on
      resistance--the ability to prevent infection or limit parasite replication. The
      genetics, physiology, and evolutionary ecology of such traits are now relatively
      well understood. During the last few years it has been realized that another,
      conceptually different type of defence also plays an important role in animal
      host-parasite interactions. This type of defence is called tolerance, and can be
      defined as the ability to limit the health effects of parasites without
      preventing infection or controlling parasite replication. Our understanding of
      the causes and consequences of variation in tolerance is, however, still
      rudimentary. Three recent studies shed light on these questions. In a study of
      HIV in humans, Regoes et al. show that an MHC class I gene affects not only
      resistance (as previously known) but also tolerance. In a study of voles, Jackson
      et al. identify a transcription factor mediating age differences in tolerance to
      macroparasites. Finally, Hayward et al. demonstrate that tolerance to intestinal
      parasites in sheep is under positive directional selection, but that most of the
      variation is environmentally induced rather than heritable. These studies
      increase our knowledge of the genetic and physiological sources of variation in
      tolerance, and how this variation affects Darwinian fitness. In addition, they
      illustrate different approaches to untangle tolerance from other factors
      determining the health effects of infectious disease.

PMID- 25369061
TI  - Assessment of toxic effects of the methanol extract of Citrus macroptera Montr.
      Fruit via biochemical and hematological evaluation in female Sprague-Dawley rats.
AB  - Citrus macroptera Montr. (C. macroptera) is locally known as Satkara. The fruit
      of this plant is used as appetite stimulant and in the treatment of fever. This
      study therefore aimed to evaluate the toxic effects of the fruit extract using
      some biochemical and hematological parameters in rat model. The effects of
      methanol extract of Citrus macroptera Montr. fruit administered at 250, 500 and
      1000 mg/kg body weight were investigated on hematological and biochemical
      parameters in Sprague-Dawley female rats. Moreover, histopathological study was
      performed to observe the presence of pathological lesions in primary body organs.
      The extract presented no significant effect on body weight, percent water
      content, relative organ weight and hematological parameters in rat. Significant
      decrease from control group was observed in the levels of triglyceride, total
      cholesterol, low density lipoprotein and very low density lipoprotein; thus
      leading to significant decrease of cardiac risk ratio, castelli's risk index-2,
      atherogenic coefficient and atherogenic index of plasma at all doses. 500 mg/kg
      dose significantly decreased alkaline phosphatase (P<0.05), 1000 mg/kg dose
      significantly increased high density lipoprotein cholesterol (P<0.05) and 250
      mg/kg dose significantly decreased the level of glycated hemoglobin (P<0.05) from
      the control group. There were no significant alterations observed with other
      serum biochemical parameters. Histopathological study confirmed the absence of
      inflammatory and necrotic features in the primary body organs. Study results
      indicate that methanolic fruit extract is unlikely to have significant toxicity.
      Moreover, these findings justified the cardio-protective, moderate hepato
      protective and glucose controlling activities of the fruit extract. 

PMID- 25369062
TI  - Symptoms of an intrauterine hematoma associated with pregnancy complications: a
      systematic review.
AB  - OBJECTIVE: To evaluate the predictive value of the symptoms of an intrauterine
      hematoma (IUH) for adverse pregnancy outcomes. METHODS: A literature review was
      performed with the search terms, including
      intrauterine/subchorionic/retroplacental/subplacental
      hematoma/hemorrhage/bleeding/collection/fluid, covering the period from January,
      1981 to January, 2014. We just focused on the pregnancy outcomes associated with
      different symptoms of an IUH. RESULTS: It is generally agreed that a
      retroplacental, posterior or subchorionic in the fundus of uterus, and/or
      persistent IUH is associated with adverse outcomes in the ongoing pregnancy.
      However, the prognosis value of both volume and gestational age at diagnosis of
      IUH still remains controversial. Some researchers argue that a large IUH is
      associated with an increased risk of adverse events during pregnancy while others
      refuted. It is believed by some that the earlier an IUH was detected, the higher
      the risk for adverse outcomes would be, while no or weak association were
      reported by other studies. The prognostic value of the simultaneous presence of
      vaginal bleeding on pregnancy outcome is also controversial. CONCLUSIONS: Both
      the position relative to the placenta or uterus and duration of IUH have strong
      predictive value on the prognosis in the ongoing pregnancy. However, the
      prognostic values of the IUH volume, gestational age at diagnosis and the
      simultaneous presence of vaginal bleeding remain controversial up to now.
      Moreover, most of previous reports are small, uncontrolled studies with
      incomplete information. Prospective, large sample, cohorts studies which take all
      detailed symptoms of an IUH into consideration are needed when we evaluate its
      clinical significance in the prognosis of pregnancy.

PMID- 25369063
TI  - Adding more junior residents may worsen emergency department crowding.
AB  - BACKGROUND: Although increasing staff numbers during shifts when emergency
      department (ED) crowding is severe can help meet patient demand, it remains
      unclear how different types of added staff, particularly junior residents, may
      affect crowding. METHODS: To identify associations between types of staff and ED
      crowding, we conducted a cross-sectional, single-center study in the ED of a
      large, teaching hospital in Japan between January and December 2012. Patients who
      visited the ED during the study period were enrolled. We excluded (1) patients
      previously scheduled to visit the ED, and (2) neonates transferred from other
      hospitals. During the study period, 27,970 patients were enrolled. Types of staff
      analyzed were junior (first and second year) residents, senior (third to fifth
      year) residents, attending (board-certified) physicians, and nurses. A
      generalized linear model was applied to length of ED stay for all patients as
      well as admitted and discharged patients to quantify an association with the
      additional staff. RESULTS: In the model, addition of one attending physician or
      senior resident was associated with decreased length of ED stay for total
      patients by 3.88 or 1.64 minutes, respectively (95% CI, 2.20-5.56 and 0.81-2.48
      minutes); while additional nursing staff had no association. Surprisingly,
      however, one additional junior resident was associated with prolonged length of
      ED stay for total patients by 0.97 minutes (95% CI 0.37-1.57 minutes) and for
      discharged patients by 1.01 minutes (95% CI 0.45-1.59 minutes). CONCLUSION:
      Staffing adjustments aimed at alleviating ED crowding should focus on adding more
      senior staff during peak-volume shifts.

PMID- 25369064
TI  - DNA methylation and transcription in a distal region upstream from the bovine
      AlphaS1 casein gene after once or twice daily milking.
AB  - Once daily milking (ODM) induces a reduction in milk production when compared to
      twice daily milking (TDM). Unilateral ODM of one udder half and TDM of the other
      half, enables the study of underlying mechanisms independently of inter
      individual variability (same genetic background) and of environmental factors.
      Our results show that in first-calf heifers three CpG, located 10 kb upstream
      from the CSN1S1 gene were methylated to 33, 34 and 28%, respectively, after TDM
      but these levels were higher after ODM, 38, 38 and 33%, respectively. These
      methylation levels were much lower than those observed in the mammary gland
      during pregnancy (57, 59 and 50%, respectively) or in the liver (74, 78 and 61%,
      respectively). The methylation level of a fourth CpG (CpG4), located close by
      (29% during TDM) was not altered after ODM. CpG4 methylation reached 39.7% and
      59.5%, during pregnancy or in the liver, respectively. CpG4 is located within a
      weak STAT5 binding element, arranged in tandem with a second high affinity STAT5
      element. STAT5 binding is only marginally modulated by CpG4 methylation, but it
      may be altered by the methylation levels of the three other CpG nearby. Our
      results therefore shed light on mechanisms that help to explain how milk
      production is almost, but not fully, restored when TDM is resumed (15.1 +/- 0.2
      kg/day instead of 16.2 +/- 0.2 kg/day, p<0.01). The STAT5 elements are 100 bp
      away from a region transcribed in the antisense orientation, in the mammary gland
      during lactation, but not during pregnancy or in other reproductive organs (ovary
      or testes). We now need to clarify whether the transcription of this novel RNA is
      a consequence of STAT5 interacting with the CSN1S1 distal region, or whether it
      plays a role in the chromatin structure of this region.

PMID- 25369065
TI  - Rapid response of hydrological loss of DOC to water table drawdown and warming in
      Zoige peatland: results from a mesocosm experiment.
AB  - A large portion of the global carbon pool is stored in peatlands, which are
      sensitive to a changing environment conditions. The hydrological loss of
      dissolved organic carbon (DOC) is believed to play a key role in determining the
      carbon balance in peatlands. Zoige peatland, the largest peat store in China, is
      experiencing climatic warming and drying as well as experiencing severe
      artificial drainage. Using a fully crossed factorial design, we experimentally
      manipulated temperature and controlled the water tables in large mesocosms
      containing intact peat monoliths. Specifically, we determined the impact of
      warming and water table position on the hydrological loss of DOC, the exported
      amounts, concentrations and qualities of DOC, and the discharge volume in Zoige
      peatland. Our results revealed that of the water table position had a greater
      impact on DOC export than the warming treatment, which showed no interactive
      effects with the water table treatment. Both DOC concentration and discharge
      volume were significantly increased when water table drawdown, while only the DOC
      concentration was significantly promoted by warming treatment. Annual DOC export
      was increased by 69% and 102% when the water table, controlled at 0 cm, was
      experimentally lowered by -10 cm and -20 cm. Increases in colored and aromatic
      constituents of DOC (measured by Abs(254 nm), SUVA(254 nm), Abs(400 nm), and
      SUVA(400 nm)) were observed under the lower water tables and at the higher peat
      temperature. Our results provide an indication of the potential impacts of
      climatic change and anthropogenic drainage on the carbon cycle and/or water
      storage in a peatland and simultaneously imply the likelihood of potential damage
      to downstream ecosystems. Furthermore, our results highlight the need for local
      protection and sustainable development, as well as suggest that more research is
      required to better understand the impacts of climatic change and artificial
      disturbances on peatland degradation.

PMID- 25369066
TI  - Long-term prediction of the Arctic ionospheric TEC based on time-varying
      periodograms.
AB  - Knowledge of the polar ionospheric total electron content (TEC) and its future
      variations is of scientific and engineering relevance. In this study, a new
      method is developed to predict Arctic mean TEC on the scale of a solar cycle
      using previous data covering 14 years. The Arctic TEC is derived from global
      positioning system measurements using the spherical cap harmonic analysis mapping
      method. The study indicates that the variability of the Arctic TEC results in
      highly time-varying periodograms, which are utilized for prediction in the
      proposed method. The TEC time series is divided into two components of periodic
      oscillations and the average TEC. The newly developed method of TEC prediction is
      based on an extrapolation method that requires no input of physical observations
      of the time interval of prediction, and it is performed in both temporally
      backward and forward directions by summing the extrapolation of the two
      components. The backward prediction indicates that the Arctic TEC variability
      includes a 9 years period for the study duration, in addition to the well
      established periods. The long-term prediction has an uncertainty of 4.8-5.6 TECU
      for different period sets. 

PMID- 25369067
TI  - Interplay of agency and ownership: the intentional binding and rubber hand
      illusion paradigm combined.
AB  - The sense of agency (SoA) refers to the phenomenal experience of initiating and
      controlling an action, whereas the sense of ownership (SoO) describes the feeling
      of myness an agent experiences towards his or her own body parts. SoA has been
      investigated with intentional binding paradigms, and the sense of ownership (SoO)
      with the rubber-hand illusion (RHI). We investigated the relationship between SoA
      and SoO by incorporating intentional binding into the RHI. Explicit and implicit
      measures of agency (SoA-questionnaire, intentional binding) and ownership (SoO
      questionnaire, proprioceptive drift) were used. Artificial hand position
      (congruent/incongruent) and mode of agent (self-agent/other-agent) were
      systematically varied. Reported SoO varied mainly with position (higher in
      congruent conditions), but also with agent (higher in self-agent conditions).
      Reported SoA was modulated by agent (higher in self-agent conditions), and
      moderately by position (higher in congruent conditions). Implicit and explicit
      agency measures were not significantly correlated. Finally, intentional binding
      tended to be stronger in self-generated than observed voluntary actions. Results
      provide further evidence for a partial double dissociation between SoA and SoO,
      empirically distinct agency levels, and moderate intentional binding differences
      between self-generated and observed voluntary actions. 

PMID- 25369071
TI  - Humanized mouse models for type 1 diabetes including pancreatic islet
      transplantation.
AB  - We comment here on the suitability of available mouse models for type 1 diabetes
      research including research on therapeutic pancreatic islet transplantation. The
      major emphasis will be laid on models that require minimal invasive procedures.
      Most biological processes are too complex for a complete recapitulation in a test
      tube. The study of innate or even adaptive immune responses involves a number of
      different cell types and organs making in vitro studies unreliable but also
      providing extreme challenges for the use of surrogate model organisms. Studying
      these processes directly in humans is impossible due to ethical and technical
      constraints. To resolve this problem small animal models such as mice or rats are
      frequently used to study mechanisms of complex diseases. This has brought much
      insight into hematopoiesis and immune cell function including type 1 diabetes
      (T1D); however, 65 million years of evolution introduced striking differences
      between mice and humans 1. In fact, none of the many suggested therapies arising
      from studies using mice 2 3 that have promised prevention or even reversion of
      T1D made it into the clinic yet 4 5 6. The reason for this are major species
      specific differences between rodents and humans regarding the immune system and
      beta cells.

PMID- 25369069
TI  - Diuretic and Anti-Inflammatory Activities of the Microencapsulated Acrocomia
      aculeata (Arecaceae) Oil on Wistar Rats.
AB  - Acrocomia aculeata, popularly known as "bocaiuva," is widely acknowledged in
      culinary and traditional medicines to treat cardiovascular diseases, a combined
      effect with diuretics that are also used for hypertension. However, there are no
      scientific data published to support its use as functional food and its
      ethnopharmacological use. This study intended to determine the composition of
      fatty acids of the pulp oil and evaluate the diuretic action and anti
      inflammatory activity of the in natura and microencapsulated oil orally
      administrated on rats. The obtained results confirm the prevalence of
      monounsaturated fatty acids (68.51%), especially oleic acid (65.68%+/-1.05%), in
      the oil from the bocaiuva pulp. The in natura A. aculeata oil has diuretic
      (P<.01) and anti-inflammatory potential, which promoted a marked inhibition on
      the hind paw edema induced by carrageenan (67%+/-7% after 2 h) (P<.01). In
      addition, results show that the oral administration of the bocaiuva oil at 300
      (P<.05) and 700 (P<.05) mg/kg doses significantly inhibited the leukocyte
      migration induced by carrageenan to the pleural cavity in rats. The inhibitions
      equaled 91%+/-3% and 81%+/-16%, respectively. The microencapsulated oil also
      showed antiedematogenic (P<.01) as well as diuretic activities (P<.01). The
      microencapsulation by complex coacervation was shown to be a technique that
      favors the bioavailability and preservation of bioactive components of the
      bocaiuva oil.

PMID- 25369070
TI  - MicroRNAs expression in triple negative vs non triple negative breast cancer in
      Tunisia: interaction with clinical outcome.
AB  - INTRODUCTION: MicroRNAs are small, non coding regulatory molecules containing
      approximately 21 to 25 nucleotides. They function as controllers of expression at
      post transcriptional levels of most human protein-coding genes and play an
      essential role in cell signaling pathways. The objective of the present study is
      to evaluate the expression profile of the following micro-RNAs: miR-10b, miR-17,
      miR-21, miR-34a, miR-146a, miR-148a and miR-182, and to determine their possible
      interaction in triple-negative and non triple-negative primary breast cancers
      based on clinical outcome. METHODS: 60 triple-negative and non triple-negative
      breast cancer cases, along with their corresponding normal samples were
      investigated in relation to the expression of the seven studied miRNAs using qPCR
      Syber Green. RESULTS: We observed that miR-21, miR-146a and miR-182 were
      significantly over expressed in triple negative breast cancer. Moreover, miR-10b,
      miR-21 and miR-182 were significantly associated to lymph node metastases
      occurrence in triple negative breast carcinoma while only miR-10b was associated
      with grade III in non triple negative breast cancer cases. Almost all the
      analyzed microRNAs were strongly associated with patients' genico-obstetric
      history in non triple negative breast cancer cases except for miR-34a. All the
      studied microRNAs were strongly correlated with the use of the contraceptive
      pills in non triple negative breast cancer groups. The additive effect of
      hormonal factors in triple negative breast cancer cases showed an association
      with all the studied miRs except for miR-34 and miR-146a. CONCLUSION: The studied
      microRNAs are strongly influenced by environmental factors especially with
      hormonal patients' history. Moreover, miR-10b, miR-21 and miR-182 could be
      defined as biomarkers in breast cancer to predict both lymph node metastases and
      grade III occurrence.

PMID- 25369072
TI  - Prevalence of hypothyroidism in patients with dyslipidemia: Tehran Thyroid Study
      (TTS).
AB  - Hypothyroidism is a relatively common endocrine disorder usually accompanied with
      changes in serum lipid profiles. The purpose of this study was to assess the
      association between dyslipidemia and hypothyroidism in a population-based study.
      In this cross-sectional study, 2,315 dyslipidemic patients, aged 20-90 years
      (mean age: 38.1 +/- 13.2 years), were selected from among 5,760 participants of
      Tehran Thyroid Study and divided into 3 groups, the subclinical hypothyroid,
      overt hypothyroid, and euthyroid subjects, based on national reference ranges.
      Serum lipid profiles, free thyroxine (FT4), thyroid stimulating hormone (TSH),
      and thyroid peroxidase antibody (TPOAb) were measured in all subjects. In
      subjects with dyslipidemia and nondyslipidemia, the prevalence of subclinical was
      7% and 4.1%, respectively, and for clinical hypothyroidism 3% and 1.2%,
      respectively. In dyslipidemic subjects, the mean low density lipoprotein
      cholesterol (LDL-C) levels differed significantly (p = 0.03) among the overt
      hypothyroid (144.3 +/- 36.1), subclinical hypothyroid (129.3 +/- 39.2), and
      euthyroid (132.7 +/- 39.0) groups. In the overt hypothyroid group, mean total
      cholesterol level was higher than in the normal group, but not significant. There
      were no differences in median triglycerides (TG) and mean high density
      lipoprotein-cholesterol (HDL-C) levels among the 3 groups mentioned. After
      adjusting for age and sex, hypothyroidism was not related to elevated serum lipid
      profiles in patient with dyslipidemia. In conclusion, there is significant
      difference in the prevalence of subclinical and clinical hypothyroidism between
      nondyslipidemic and dyslipidemic subjects; after adjustment for age and sex the
      presence of dyslipidemia did not predict the presence of hypothyroidism.

PMID- 25369073
TI  - Training, detraining, and retraining effects on glycemic control and physical
      fitness in women with type 2 diabetes.
AB  - Little is known about the detraining and retraining effects of exercise in
      patients with diabetes. The purpose of the present study was to investigate the
      effects of training, detraining, and retraining, using a combined strength and
      aerobic exercise program on glycemic control in women with type 2 diabetes.
      Thirteen postmenopausal women with type 2 diabetes (n = 13, age: 55.8 +/- 5.1
      years) followed a supervised aerobic and strength training program for 9 months,
      which was interrupted for 3 months (detraining) and resumed again for a period of
      9 months (retraining). Anthropometric characteristics, glycemic control, and
      physical fitness were determined at baseline and after 9, 12, and 21 months.
      Training induced a small reduction in body mass index (BMI: -3.3%, 95% CI -5.1 to
      -1.5%), a moderate decrease in fasting plasma glucose (FPG: -12.0%, 95% CI -20.70
      to -3.2%), glycosylated hemoglobin (HbA1c: -4.7%, 95% CI -12.1 to 2.7%), and a
      large decrease in postprandial glucose (PPG: - 12.1%, 95% CI -20.2 to -4.1%). In
      addition, there was an increase in power output (20.2%, 95% CI 6.9 to 33.6%) and
      total muscle strength (33.8%, 95% CI 21.4 to 46.1%). Detraining reversed PPG,
      HbA1c, and physical fitness. Resumption of training, however, led to a moderate
      decrease in BMI (-5.4%, 95% CI -8.1 to -2.7%), PPG (-9.5%, 95% CI -19.4 to 0.3%),
      and HbA1c (-6.8%, 95% CI -14.1 to 0.5%), and to large changes in FPG (-20.9%, 95%
      CI -31.9 to -9.9%), power output (33.1%, 95% CI 17.9 to 48.4%) and total muscle
      strength (48.2%, 95% CI 34.0 to 62.4%) compared to baseline. Thus, systematic
      training improves body composition, glycemic control and physical fitness in
      patients with type 2 diabetes. The cessation of exercise brings about negative
      alterations, while retraining restores all beneficial adaptations and improves
      them even more. Therefore, diabetic patients should follow a regular and an
      uninterrupted exercise program throughout life in order to control glucose
      metabolism and improve health.

PMID- 25369074
TI  - Fructose-Rich Diet-Induced Changes in the Expression of the Renin Angiotensin
      System Molecules in the Heart of Ovariectomized Female Rats Could be Reversed by
      Estradiol.
AB  - The renin-angiotensin system has been implicated in the development of metabolic
      syndrome and appears to be a key in the local tissue control of normal cardiac
      functions. Physiological concentrations of estrogens have been shown to be
      cardioprotective, especially against the damaging effects of fructose-rich diet.
      The aim of the study was to investigate the expression of the renin-angiotensin
      system molecules with potentially deleterious effect on the heart (angiotensin
      converting enzyme and angiotensin II type 1 receptor) and those with potentially
      protective effects, (angiotensin-converting enzyme 2 and angiotensin II type 2
      receptor), in ovariectomized fructose fed female rats with 17beta-estradiol
      replacement. Real-time PCR and Western blot analysis were used for quantification
      of gene and protein expression in the heart. Fructose diet increased the
      expression of angiotensin-converting enzyme and angiotensin II type 1 receptor
      and decreased the expression of angiotensin-converting enzyme 2 and angiotensin
      II type 2 receptor. On the other hand, estradiol replacement seems to undo
      fructose diet effects on cardiac renin-angiotensin system. Downregulation of
      angiotensin-converting enzyme and angiotensin II type 1 receptor, and reversion
      of expression of both potentially protective molecules, angiotensin-converting
      enzyme 2 and angiotensin II type 2 receptor, to the control level in cardiac
      tissue took place. Obtained results suggest that estradiol may reverse the
      harmful effect of fructose-rich diet on the expression of renin-angiotensin
      system molecules. These findings may also be important in further research of
      phenotypes like insulin resistance, metabolic syndrome, and following
      cardiovascular pathology in females. 

PMID- 25369075
TI  - Locus of control, self-efficacy, and the mediating effect of outcome control:
      predicting course-level and global outcomes in an academic context.
AB  - BACKGROUND AND OBJECTIVES: The current study utilizes Skinner's framework to
      examine the unique contributions of internal locus of control, self-efficacy, and
      perceived outcome control over course performance on students' academic
      experiences. METHOD: Undergraduate students (N = 225) took part in a longitudinal
      study and completed two surveys (Time 1: just before their mid-term exams; Time
      2: just before their final exam in the same semester). RESULTS: Both locus of
      control and self-efficacy at Time 1 predicted course-level perceived control over
      course performance at Time 2. Student-level perceived control over course
      performance at Time 2 mediated the relationship between self-efficacy at Time 1
      and course-level perseverance, course-specific stress, and course enjoyment at
      Time 2. For global perceived stress and life satisfaction measured at Time 2,
      both locus of control and self-efficacy at Time 1 had only a direct effect on
      global perceived stress at Time 2, but only self-efficacy at Time 1 predicted
      life satisfaction at Time 2. CONCLUSION: Both locus of control and self-efficacy
      uniquely contribute to students' academic experiences. Student-level perceived
      control plays an important mediating role between locus of control and self
      efficacy at Time 1, and course-level perseverance, course-specific stress, and
      course enjoyment at Time 2.

PMID- 25369076
TI  - Analysis of age and disease status as predictors of thyroid cancer-specific
      mortality using the Surveillance, Epidemiology, and End Results database.
AB  - BACKGROUND: Age at diagnosis is incorporated into all relevant staging systems
      for differentiated thyroid carcinoma (DTC). There is growing evidence that a
      specific age cutoff may not be ideal for accurate risk stratification. We sought
      to evaluate the interplay between age and oncologic variables in patients with
      DTC using the largest cohort to date. METHODS: The Surveillance, Epidemiology,
      and End RESULTS (SEER) database was queried to identify patients with DTC as
      their only malignancy for the period 1973 to 2009. Multivariate analyses using a
      range of age cutoffs and age subgroupings were utilized in order to search for an
      optimal age that would provide the most significant risk stratification between
      young and old patients. The primary outcome was disease-specific survival (DSS)
      and covariates included: age, race, sex, tumor/nodal/metastasis (TNM) stage,
      decade of diagnosis, and radioactive iodine therapy. RESULTS: A total of 85,740
      patients were identified. Seventy-six percent of patients were American Joint
      Committee on Cancer (AJCC) stage I, 8% were stage II, 7% were stage III, and 8%
      were stage IV. Age over 45 years (hazard ratio [HR] 19.2, p<0.001) and metastatic
      disease (HR 13.1, p<0.001) were the strongest predictors of DSS. Other factors
      that significantly predicted DSS included: not receiving radioactive iodine (RAI;
      HR 1.3, p=0.002), T3 (HR 2.6, p<0.001), and T4 disease (HR 3.3, p<0.001), and
      nodal spread (HR 2.6 to 3.3, p<0.001). Female sex showed a significant protective
      effect (HR 0.7, p=0.001). Adjusting the age-group cutoff from 25 to 55 years
      showed consistently high HRs for advanced age, without a distinct change at any
      point. Comparing HRs for T, N, and M stage between young and old patient
      subgroups showed that advanced disease increased the risk for DSS regardless of
      age, and was oftentimes a worse prognosticator in young patient groups.
      CONCLUSIONS: The contribution of age at diagnosis to a patient's DSS is
      considerable, but there is no age cutoff that affords any unique risk
      stratification in patients with DTC.

PMID- 25369077
TI  - Comparative transcriptome analysis of two oysters, Crassostrea gigas and
      Crassostrea hongkongensis provides insights into adaptation to hypo-osmotic
      conditions.
AB  - Environmental salinity creates a key barrier to limit the distribution of most
      aquatic organisms. Adaptation to osmotic fluctuation is believed to be a factor
      facilitating species diversification. Adaptive evolution often involves
      beneficial mutations at more than one locus. Bivalves hold great interest, with
      numerous species living in waters, as osmoconformers, who maintain the osmotic
      pressure balance mostly by free amino acids. In this study, 107,076,589 reads
      from two groups of Crassostrea hongkongensis were produced and the assembled into
      130,629 contigs. Transcripts putatively involved in stress-response, innate
      immunity and cell processes were identified according to Gene ontology and KEGG
      pathway analyses. Comparing with the transcriptome of C. gigas to characterize
      the diversity of transcripts between species with osmotic divergence, we
      identified 182,806 high-quality single nucleotide polymorphisms (SNPs) for C.
      hongkongensis, and 196,779 SNPs for C. gigas. Comparison of 11,602 pairs of
      putative orthologs allowed for identification of 14 protein-coding genes that
      experienced strong positive selection (Ka/Ks>1). In addition, 45 genes that may
      show signs of moderate positive selection (1 >= Ka/Ks>0.5) were also identified.
      Based on Ks ratios and divergence time between the two species published
      previously, we estimated a neutral transcriptome-wide substitution mutation rate
      of 1.39 * 10(-9) per site per year. Several genes were differentially expressed
      across the control and treated groups of each species. This is the first time to
      sequence the transcriptome of C. hongkongensis and provide the most comprehensive
      transcriptomic resource available for it. The increasing amount of transcriptome
      data on Crassostrea provides an excellent resource for phylogenetic analysis. A
      large number of SNPs identified in this work are expected to provide valuable
      resources for future marker and genotyping assay development. The analysis of
      natural selection provides an innovative view on the adaptation within species
      and sets the basis for future genetic and evolutionary studies.

PMID- 25369078
TI  - The prolyl hydroxylase inhibitor dimethyloxalylglycine enhances dentin
      sialophoshoprotein expression through VEGF-induced Runx2 stabilization.
AB  - Prolyl hydroxylase (PHD) inhibitors are suggested as therapeutic agents for
      tissue regeneration based on their ability to induce pro-angiogenic responses. In
      this study, we examined the effect of the PHD inhibitor dimethyloxalylglycine
      (DMOG) on odontoblast maturation and sought to determine the underlying mechanism
      using MDPC-23 odontoblast-like cells. DMOG significantly enhanced matrix
      mineralization, confirmed by alizarin red staining and by measurement of the
      calcium content. DMOG dose-dependently increased alkaline phosphatase activity
      and the expressions of dentin sialophosphoprotein (Dspp) and osteocalcin. To
      determine the underlying events leading to DMOG-induced Dspp expression, we
      analyzed the effect of DMOG on Runx2. Knockdown of Runx2 using siRNAs decreased
      Dspp expression and prevented DMOG-induced Dspp expression. DMOG enhanced the
      transcriptional activity and level of Runx2 protein but not Runx2 transcript, and
      this enhancement was linked to the inhibitory effects of DMOG on the degradation
      of Runx2 protein. The vascular endothelial growth factor (VEGF) siRNAs profoundly
      decreased the Runx2 protein levels and inhibited the DMOG-increased Runx2
      protein. Recombinant VEGF protein treatment significantly and dose-dependently
      increased the transcriptional activity and level of the Runx2 protein but not
      Runx2 transcript. Dspp expression was also enhanced by VEGF. Last, we examined
      the involvement of the Erk mitogen-activated protein kinase and Pin1 pathway in
      VEGF-enhanced Runx2 because this pathway can regulate the stability and activity
      of the Runx2 protein. VEGF stimulated Erk activation, and the inhibitors of Erk
      and Pin1 hampered VEGF-enhanced Runx2 protein. Taken together, the results of
      this study provide evidence that DMOG can enhance Dspp expression through VEGF
      induced stabilization of Runx2 protein, and thus, suggest that DMOG can be used
      as a therapeutic tool for enhancing odontoblast maturation in dental procedures. 

PMID- 25369079
TI  - Recent HIV-1 Outbreak Among Intravenous Drug Users in Romania: Evidence for
      Cocirculation of CRF14_BG and Subtype F1 Strains.
AB  - Since 2011, Romania has faced an HIV outbreak among injecting drug users (IDUs).
      Our aim was to identify and describe clinical and epidemiological patterns of
      this outbreak. A cross-sectional study enrolled 138 IDUs diagnosed with HIV
      infection between 2011 and 2013 with 58 sexually infected individuals included as
      the control group. The IDUs had a long history of heroin abuse (10 years) and a
      recent history of new psychostimulant injection (3-4 years). Classical
      epidemiological data and molecular techniques were used to describe the
      transmission dynamics. A high prevalence of hepatitis C virus (HCV) coinfection
      was noted (98.6%) compared to the control group (10.3%) (p<0.001). IDUs had
      initially been infected with HCV. HIV infection was more recent, linked to
      starting injecting stimulants. HIV subtype analysis showed a predominance of the
      local F1 strain in both IDUs and sexually infected patients; in IDUs it also
      identified 28 CRF14_BG recombinants and six unique recombinant forms (URFs)
      between F1 and CRF14_BG. A few patients from both risk groups were infected with
      subtype B. Among IDUs, CRF14_BG was associated with a lower CD4 cell count and
      more advanced stages of disease, which correlated with CXCR4 tropism.
      Phylogenetic analysis revealed the spread of HIV through three major IDU clusters
      of recent date. Among IDUs with CRF14_BG, some reported travel abroad (Spain,
      Greece). By identifying clusters of IDUs with related viruses, molecular
      epidemiologic methods provide valuable information on patterns of HIV
      transmission that can be useful in planning appropriate harm reduction
      interventions. 

PMID- 25369081
TI  - Effects of Ebola hit children most.
AB  - International charities working in West Africa are warning that children are
      bearing the brunt of the Ebola crisis. 

PMID- 25369082
TI  - National audit of neonatal units finds improvements in care.
AB  - BABIES BORN early in the north of England are less likely to be breastfed than
      those in the south, making them more prone to infections. 

PMID- 25369080
TI  - GTP cyclohydrolase I gene polymorphisms are associated with endothelial
      dysfunction and oxidative stress in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The genetic background of atherosclerosis in type 2 diabetes mellitus
      (T2DM) is complex and poorly understood. Studying genetic components of
      intermediate phenotypes, such as endothelial dysfunction and oxidative stress,
      may aid in identifying novel genetic components for atherosclerosis in diabetic
      patients. METHODS: Five polymorphisms forming two haplotype blocks within the GTP
      cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin
      synthesis, were studied in the context of flow and nitroglycerin mediated
      dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations
      of von Willebrand factor (vWF) and malondialdehyde (MDA). RESULTS: Rs841 was
      associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641
      (which form a single haplotype) were associated with both MDA (p = 0.012, p =
      0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03
      and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also
      associated with MDA (p = 0.006). Haplotype analysis confirmed the association of
      both haplotypes with studied variables. CONCLUSIONS: Genetic variation of the
      GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM
      patients.

PMID- 25369084
TI  - NHS England chief executive unveils five-year strategy.
AB  - QUESTIONS HAVE been raised about how the health service will be funded following
      the publication of Five Year Forward View by NHS England's chief executive Simon
      Stevens. 

PMID- 25369085
TI  - Campaign to reduce complications arising from labour problems.
AB  - A FIVE-YEAR project to reduce stillbirths, early neonatal deaths and brain
      injuries occurring during labour has been launched. 

PMID- 25369086
TI  - RCN publishes advice on identifying and managing children with Ebola.
AB  - NURSES SHOULD apply the same measures for identifying and caring for children
      with suspected Ebola virus as required for adult nursing care, according to the
      RCN. 

PMID- 25369087
TI  - Call to support orphans of outbreak, as death toll rises.
AB  - INTERNATIONAL CHARITIES are rallying to provide food, shelter, health care and
      support for children orphaned by the outbreak of the Ebola virus. 

PMID- 25369088
TI  - Breastfeeding improves mother and baby emotional wellbeing.
AB  - THE UNITED Nations International Children's Emergency Fund's (Unicef) Baby
      Friendly Initiative works with health and public services to improve standards of
      care by supporting breastfeeding and parent-infant relationships. 

PMID- 25369089
TI  - Nurse picks up the challenge of building interdisciplinary links.
AB  - WHEN LEADING children's nurse and academic Judith Ellis was appointed chief
      executive of the Royal College of Paediatrics and Child Health (RCPCH), she
      became the first nurse to take up this role since the doctors' organisation was
      founded in 1996. 

PMID- 25369094
TI  - Research essentials: Implementing findings from clinical projects to influence
      practice.
AB  - IMPLEMENTING AND evaluating findings from clinical projects is an essential part
      of ensuring that care is based on the best available evidence and is responsive
      to local needs and settings. The 'plan', 'do', 'study', 'act' (PDSA) cycle
      (Figure 1) is one framework for planning projects and improving services.

PMID- 25369095
TI  - Research and commentary: Using the web as an education intervention for families
      of children with atopic dermatitis.
AB  - Background Atopic dermatitis, also known as atopic eczema, is a chronic
      inflammatory disorder of the skin characterised by acute exacerbations of skin
      dryness, rash and pruritus. It is often associated with allergic disorders such
      as asthma, food allergies and rhinitis. 

PMID- 25369096
TI  - Efficacy of web resources in meeting parental need for information.
AB  - To manage their child's long-term condition, parents require a range of support
      interventions to meet their information and emotional needs (Hallstrom and
      Elander 2007). There is increasing recognition of the value of social media tools
      and platforms to share information on-line (Blackburn and Reid 2005).

PMID- 25369097
TI  - We must stop the assaults.
AB  - IF THE estimate that up to 65,000 girls aged up to 13 years in the UK are at risk
      of female genital mutilation (FGM) is correct, this would make it the most
      prevalent form of severe physical child abuse in the country. 

PMID- 25369098
TI  - Student voice - Learning to respond to patients' families.
AB  - I HAVE ENCOUNTERED many challenging situations in my children's and general
      internship placements. One that stands out was when I was taking care of an adult
      patient who had undergone an endoscopic procedure - and it is one that has
      resonance in children's nursing. A biopsy was also taken of some tissue and it
      was reported that it was likely the patient had cancer. 

PMID- 25369102
TI  - Blended food for enteral feeding via a gastrostomy.
AB  - A blended diet for enteral nutrition is defined as home-made everyday food
      blended to a smooth 'single cream' consistency. At present, blended food is not
      recommended as a first choice. However, the wishes of parents who prefer to use
      blended food for their child need to be respected, and hospice policy for
      Children's Hospice South West is to replicate home conditions as far as possible.
      Therefore guidelines have been created for use of a blended diet. However,
      benefits in physical and emotional health need to be balanced against risks of
      tube blockage, contamination and digestive upsets. 

PMID- 25369103
TI  - Nurses' knowledge about the double-checking process for medicines administration.
AB  - This study aimed to evaluate nurses' knowledge, perceptions and opinions of
      double-checking medication administration in a UK children's hospital. Of 119
      questionnaires distributed, 48 were returned. Only 30 respondents had seen a
      written version of the hospital double-checking policy. More than half stated
      that they had not received formal training in double-checking medications. Of 35
      nurses providing a definition of double-checking, one gave a response that
      reflected hospital policy. Most respondents thought that staffing, workloads and
      interruptions affected adherence to double-checking; 15 reported that double
      checking was easier to do at night; and the results suggested that lack of
      knowledge and of clear guidelines contributed to medication errors. 

PMID- 25369104
TI  - Intensive care of children with burn injuries and the role of the
      multidisciplinary team.
AB  - Trauma from burns and scalds in children is more common and more damaging than in
      adults, and may indicate abuse. The main goal of intensive care of an acute burn
      is to limit the extent of the systemic insult. Effective treatment of such acute
      physiological changes requires experienced monitoring by multidisciplinary teams,
      following appropriate emergency protocols at specialised burn centres in cases of
      major trauma. First aid involves maintaining a patent airway, supporting
      circulation and respiration, arresting the burning, managing pain and distress,
      reducing infection and considering transfer to specialist care. Advances in
      techniques and treatment have increased survival rates and ultimate quality of
      life, but education and prevention programmes are still required at all levels to
      reduce the incidence of burns among children. 

PMID- 25369105
TI  - Fundamentals of chronic pain in children and young people. Part 2.
AB  - Chronic pain is common in childhood and can have severe physical and
      psychological consequences but, unlike acute pain, it is not always recognised by
      nurses and other health professionals. A holistic and multidisciplinary approach
      to treatment is required and nurses can play a significant role in helping
      children and families to cope with the negative effects of the condition. The
      first part of this article, published in October, looked at the prevalence,
      anatomy and physiology of pain, and factors associated with chronic pain and its
      consequences. In part 2, assessment strategies as well as pharmacological and
      psychological interventions, are discussed, along with self-help programmes and
      strategies that can be used to aid sleep and help the child at school manage
      their pain. 

PMID- 25369107
TI  - Experiencing your own orthognathic surgery: a personal case report.
AB  - There has been much research on minimizing the side effects of orthognathic
      surgery. However, there are very few doctors and researchers who themselves have
      undergone this surgery. This case report describes the findings of a
      maxillofacial surgeon who underwent combined orthodontic and orthognathic
      treatment for correction of Class II malocclusion. In March 2012, the surgeon was
      referred to an orthodontist, and an orthodontic examination revealed a Class II,
      division 2, malocclusion with a traumatic palatal bite and attrition of the lower
      front teeth. The patient underwent alignment of the upper and lower arches,
      followed by a bilateral sagittal split osteotomy. During this treatment, he made
      many interesting observations and learned much as a patient, which can have
      implications in improving the outcomes and quality of care for patients receiving
      such treatment. Thus, this case report aims to provide a critical perspective of
      the surgical procedure and treatment from the viewpoint of a maxillofacial
      surgeon who himself experienced the surgery as a patient.

PMID- 25369106
TI  - Tempo and mode of gene duplication in mammalian ribosomal protein evolution.
AB  - Gene duplication has been widely recognized as a major driver of evolutionary
      change and organismal complexity through the generation of multi-gene families.
      Therefore, understanding the forces that govern the evolution of gene families
      through the retention or loss of duplicated genes is fundamentally important in
      our efforts to study genome evolution. Previous work from our lab has shown that
      ribosomal protein (RP) genes constitute one of the largest classes of conserved
      duplicated genes in mammals. This result was surprising due to the fact that
      ribosomal protein genes evolve slowly and transcript levels are very tightly
      regulated. In our present study, we identified and characterized all RP
      duplicates in eight mammalian genomes in order to investigate the tempo and mode
      of ribosomal protein family evolution. We show that a sizable number of
      duplicates are transcriptionally active and are very highly conserved.
      Furthermore, we conclude that existing gene duplication models do not readily
      account for the preservation of a very large number of intact retroduplicated
      ribosomal protein (RT-RP) genes observed in mammalian genomes. We suggest that
      selection against dominant-negative mutations may underlie the unexpected
      retention and conservation of duplicated RP genes, and may shape the fate of
      newly duplicated genes, regardless of duplication mechanism. 

PMID- 25369108
TI  - Effect of lanreotide on polycystic liver and kidneys in autosomal dominant
      polycystic kidney disease: an observational trial.
AB  - BACKGROUND & AIM: Several trials have demonstrated that somatostatin analogues
      decrease liver volume in mixed populations of patients with autosomal dominant
      polycystic kidney disease (ADPKD) and isolated polycystic liver disease. Chronic
      renal dysfunction in ADPKD may affect treatment efficacy of lanreotide and
      possibly enhances risk for adverse events. The aim of this open-label clinical
      trial (RESOLVE trial) was to assess the efficacy of 6-month lanreotide treatment,
      120 mg, subcutaneously every 4 weeks in ADPKD patients with symptomatic
      polycystic liver disease. METHODS: Primary outcome was change in liver volume
      after 6 months; secondary outcomes were changes in kidney volume, estimated
      glomerular filtration rate (eGFR), symptom relief and health-related quality of
      life (Euro-Qol5D). We excluded patients with an eGFR <30 ml/min/1.73 m(2) . We
      used the Wilcoxon signed-rank test or paired two-sided t-test to analyze within
      group differences. RESULTS: We included 43 ADPKD patients with polycystic liver
      disease (84% female, median age 50 years, mean eGFR 63 ml/min/1.73 m(2) ). Median
      liver volume decreased from 4859 ml to 4595 ml (-3.1%; P < 0.001), and median
      kidney volume decreased from 1023 ml to 1012 ml (-1.7%; P = 0.006). eGFR declined
      3.5% after the first injection, remained stable up to study end, to decline again
      after lanreotide withdrawal. Lanreotide significantly relieved post-prandial
      fullness, shortness of breath and abdominal distension. Three participants had a
      suspected episode of hepatic or renal cyst infection during this study.
      CONCLUSION: Lanreotide reduced polycystic liver and kidney volumes and decreases
      symptoms in ADPKD patients. Moreover, eGFR decreased acutely after starting
      lanreotide, stabilized thereafter and declined again after withdrawal. TRIAL
      REGISTRATION NUMBER: Clinical trials.gov NCT01354405 (REGISTRATION: 13 May 2011).

PMID- 25369109
TI  - Decohesion kinetics in polymer organic solar cells.
AB  - We investigate the role of molecular weight (MW) of the photoactive polymer
      poly(3-hexylthiophene) (P3HT) on the temperature-dependent decohesion kinetics of
      bulk heterojunction (BHJ) organic solar cells (OSCs). The MW of P3HT has been
      directly correlated to its carrier field effect mobilities and the ambient
      temperature also affects OSC in-service performance and P3HT arrangement within
      the BHJ layer. Under inert conditions, time-dependent decohesion readily occurs
      within the BHJ layer at loads well below its fracture resistance. We observe that
      by increasing the MW of P3HT, greater resistance to decohesion is achieved.
      However, failure consistently occurs within the BHJ layer representing the
      weakest layer within the device stack. Additionally, it was found that at
      temperatures below the glass transition temperature (~41-45  degrees C),
      decohesion was characterized by brittle failure via molecular bond rupture. Above
      the glass transition temperature, decohesion growth occurred by a viscoelastic
      process in the BHJ layer, leading to a significant degree of viscoelastic
      deformation. We develop a viscoelastic model based on molecular relaxation to
      describe the resulting behavior. The study has implications for OSC long-term
      reliability and device performance, which are important for OSC production and
      implementation.

PMID- 25369111
TI  - Insulin sensitivity and leptin in women with PCOS.

PMID- 25369110
TI  - Radiotherapy alone in patients with Merkel cell carcinoma: the Westmead Hospital
      experience of 41 patients.
AB  - OBJECTIVES: To review the role of radiotherapy as treatment (RTx) alone in
      patients with Merkel cell carcinoma (MCC). METHODS: Data on 41 patients with MCC
      treated with RTx alone between 1993 and 2013 at Westmead Hospital, Sydney, were
      reviewed and analysed. RESULTS: The patients' median age was 80 (range 45-96
      years) among 18 (44%) women and 23 (56%) men. All but one patient were white and
      six (15%) were immunosuppressed. Most (59%) were irradiated at initial diagnosis
      with the remainder treated in the relapse setting. The median duration of follow
      up was 39 months. Head and neck was the most frequently treated site (63%). The
      median lesion size was 30 mm (range 5-130 mm). The in-field control rate was 85%.
      Most out-of-field relapses were to visceral organs. Overall survival at 5 years
      was 40%. CONCLUSIONS: Patients with MCC treated with RTx alone experience a high
      likelihood of obtaining in-field disease control. Doses of 50-55 Gy in 20-25
      fractions are recommended but lower doses (25 Gy in five fractions) are still
      effective. A minority will be cured with many patients subsequently dying of
      systemic relapse.

PMID- 25369112
TI  - Evidence for facilitation of Culex pipiens (Diptera: Culicidae) life history
      traits by the nonnative invasive shrub Amur honeysuckle (Lonicera maackii).
AB  - Mosquitoes are one of the most globally important insect pests and vectors of
      human pathogens, and their populations may be facilitated or inhibited by
      anthropogenic environmental change. Invasive plant species are an important
      management concern and environmental modifier in many ecosystems; these plant
      invasions have the potential to exacerbate or diminish mosquito populations. The
      purpose of this study was to assess potential effects of a highly invasive plant,
      Lonicera maackii, on a common mosquito species Culex pipiens L., which is an
      important pathogen vector in the United States. Three microcosm assays were
      conducted to determine the responses of C. pipiens life history attributes of
      larval survivorship, growth, and pupation when subjected to leachate from two
      native plant leaves (Platanus occidentalis and Acer saccharum) and both the
      leaves and flowers of L. maackii. Only C. pipiens larvae exposed to L. maackii
      leachate pupated and emerged as adults. However, in all three assays there were
      statistically significant differences in survivorship and body size change among
      treatments, and in each assay the highest survivorship and maximum larval size
      was found in the L. maackii leachate treatments, suggesting positive effects on
      certain life history traits. This study is one of the first to demonstrate the
      potential facilitative effect of this invasive plant species on an insect vector
      and suggests that plant invasion could have positive feedbacks into mosquito
      population dynamics and, ultimately, human disease. 

PMID- 25369113
TI  - Quantitative trait loci pyramiding can improve the nutritional potential of
      tomato (Solanum lycopersicum) fruits.
AB  - Solanum lycopersicum represents an important source of antioxidants and other
      bioactive compounds. Previously two Solanum pennellii introgression lines (IL 7-3
      and IL 12-4) were identified as carrying quantitative trait loci (QTL) increasing
      fruit ascorbic acid and phenolics content. Novel tomato lines were obtained by
      pyramiding these selected QTLs in the genetic background of the cultivated line
      M82. Pyramided lines revealed significant increases of total phenolics, phenolic
      acids, ascorbic acid, and total antioxidant activity compared to parental lines
      IL 7-3 and IL 12-4 and the cultivated line M82. In addition, tomato extracts
      obtained from the pyramided lines had no cytotoxic effect on normal human cells
      while exhibiting a selective cytotoxic effect on aggressive cancer cells.
      Therefore, the present study demonstrates that it is possible to incorporate
      favorable wild-species QTLs in the cultivated genetic background to obtain
      genotypes with higher nutritional value. 

PMID- 25369114
TI  - Endocrine and fitness correlates of long-chain perfluorinated carboxylates
      exposure in Arctic breeding black-legged kittiwakes.
AB  - Increasing levels of poly- and perfluorinated alkyl substances (PFASs) have
      recently been described in Arctic biota. These emerging substances are of concern
      given their resistance to degradation and metabolization. Some studies have
      reported endocrine disrupting effects for some PFASs. However, there is a gap of
      knowledge on the potential relationships between PFASs and hormones mediating the
      life-history trade-off between reproduction and survival, such as
      glucocorticoids. The aims of this study were to (1) describe the concentrations
      of plasma perfluoroalkyl sulfonates and perfluoroalkyl carboxylates in Svalbard
      black-legged kittiwakes (Rissa tridactyla) in relation to gender and body
      condition, (2) explore the relationships between PFASs and corticosterone (the
      major glucocorticoid in birds), and (3) assess the consequences of PFAS exposure
      for reproductive success. Perfluorononanoate was positively related to body
      condition in male kittiwakes; perfluorotridecanoate and perfluorotetradecanoate
      to decreased baseline corticosterone in both sexes; and perfluorododecanoate was
      related to lower hatching success. These results underline the importance of
      considering each compound separately when investigating the hazardous effects of
      PFASs on wildlife. 

PMID- 25369115
TI  - Linear coordination fullerene C60 polymer [{Ni(Me3P)2}(MU-eta(2),eta(2)
      C60)]infinity bridged by zerovalent nickel atoms.
AB  - Coordination nickel-bridged fullerene polymer [{Ni(Me3P)2}(MU-eta(2),eta(2)
      C60)]infinity (1) has been obtained via reduction of a Ni(II)(Me3P)2Cl2 and C60
      mixture. Each nickel atom is linked in the polymer with two fullerene units by
      eta(2)-type Ni-C(C60) bonds of 2.087(8)-2.149(8) A length. Nickel atoms are
      coordinated to the 6-6 bonds of C60 as well as two trimethylphosphine ligands to
      form a four-coordinated environment around the metal centers. Fullerene cages
      approach very close to each other in the polymer with a 9.693(3) A interfullerene
      center-to-center distance, and two short interfullerene C-C contacts of 2.923(7)
      A length are formed. Polymer chains are densely packed in a crystal with
      interfullerene center-to-center distances between fullerenes from neighboring
      polymer chains of 9.933(3) A and multiple interfullerene C...C contacts. As a
      result, three-dimensional dense fullerene packing is formed in 1. According to
      optical and electron paramagnetic resonance spectra, fullerenes are neutral in 1
      and nickel atoms have a zerovalent state with a diamagnetic d(10) electron
      configuration. The density functional theory calculations prove the diamagnetic
      state of the polymer with a singlet-triplet gap wider than 1.37 eV. 

PMID- 25369116
TI  - Fluorescence line narrowing and Delta-FLN spectra in the presence of excitation
      energy transfer between weakly coupled chromophores.
AB  - The results of simulations of fluorescence line narrowed (FLN) and Delta-FLN
      spectra of weakly coupled chromophore dimers and trimers, connected by slow
      (hundreds of picoseconds) excitation energy transfer and embedded in amorphous
      solids such as proteins, are presented. The model includes wavelength-dependent
      excitation energy transfer (EET) rate distributions converted to nonidentical sub
      site distribution function (sub-SDF) (one for each EET rate), as well as
      spectral hole burning in pigments excited via EET. Emission of the donor
      molecules and realistic EET probability dependence on the donor-acceptor energy
      gap are also included. The shapes of the FLN and Delta-FLN spectra are very
      sensitive to even small variations of interpigment coupling in this weak-coupling
      regime, and proper modeling is essential for extracting correct parameters from
      the experimental spectra. Applications of the model to the trimeric FMO complex
      and the dimeric cytochrome b6f are demonstrated. 

PMID- 25369117
TI  - Bifunctional photoacids: remote protonation affecting chemical reactivity.
AB  - Reversible protonation (deprotonation) of a side-group is a useful and convenient
      way to affect the reactivity of large organic and biological molecules. We use
      bifunctional photoacids to demonstrate how the protonation state of a basic side
      group (COO(-)) controls the reactivity of the main acidic group of the photoacid
      (OH), both in the ground and the electronic excited state of 6-carboxy
      derivatives of 2-naphthol. 

PMID- 25369119
TI  - Tunable morphology of the self-assembled organic microcrystals for the efficient
      laser optical resonator by molecular modulation.
AB  - Organic single-crystalline micro/nanostructures can effectively generate and
      carry photons due to their smooth morphologies, high photoluminescence quantum
      efficiency, and minimized defects density and therefore are potentially ideal
      building blocks for the optical circuits in the next generation of miniaturized
      optoelectronics. However, the tailor-made organic molecules can be generally
      obtained by organic synthesis, ensuring that the organic molecules aggregate in a
      specific form and generate micro/nanostructures with desirable morphology and
      therefore act as the efficient laser optical resonator remains a great challenge.
      Here, the molecular modulation of the morphology on the laser optical resonator
      properties has been investigated through the preparation of the elongated
      hexagonal microplates (PHMs) and the rectangular microplates (ORMs),
      respectively, from two model isomeric organic molecules of 1,4-bis(4
      methylstyryl)benzene (p-MSB) and 1,4-bis(2-methylstyryl)benzene (o-MSB).
      Significantly, fluorescence resonance phenomenon was only observed in the
      individual ORM other than the PHM. It indicates that the rectangular resonators
      possess better light-confinement property over the elongated hexagonal
      resonators. More importantly, optically pumped lasing action was observed in the
      o-MSB rectangular morphology microplates resonator with a high Q ~ 1500 above a
      threshold of ~540 nJ/cm(2). The excellent optical properties of these
      microstructures are associated with the morphology, which can be precisely
      modulated by the organic molecular structure. These self-assembled organic
      microplates with different morphologies can contribute to the distinct
      functionality of photonics elements in the integrated optical circuits at
      micro/nanoscale. 

PMID- 25369118
TI  - Human papillomavirus in head and neck squamous cell carcinoma of unknown primary
      is a common event and a strong predictor of survival.
AB  - BACKGROUND: The purpose of this study was to examine the prevalence of human
      papillomavirus (HPV) in patients with head and neck squamous cell carcinoma of
      unknown primary (CUP). METHODS: All patients diagnosed with and treated for CUP
      between January 1, 2000, and June 1, 2011, at two Danish medical centers were
      included. All patients received a thorough diagnostic work-up, including FDG-PET,
      before being diagnosed as CUP. We determined the HPV status in all patients using
      a combination of HPV DNA PCR and p16 stain. In addition, clinical information on
      the study patients was retrieved from clinical records. RESULTS: Of the
      identified 60 patients with CUP, 13 were shown to be positive for HPV DNA,
      amounting to 22% of the study population. In addition, we were able to show a
      clear disease-free and overall-survival benefit in the HPV-positive group, with a
      hazard ratio of 0.16 (95% CI: 0.038-0.67) for over-all survival. This survival
      benefit was also apparent when adjusted for advanced age in a multivariate Cox
      regression analysis. CONCLUSION: A fairly large percentage of CUP cases are HPV
      related, and because this is related to both the location and prognosis, we
      recommend HPV testing as part of the diagnostic work-up.

PMID- 25369120
TI  - Efficacy of short-term high-dose statin pretreatment in prevention of contrast
      induced acute kidney injury: updated study-level meta-analysis of 13 randomized
      controlled trials.
AB  - BACKGROUND: There have been conflicting results across the trials that evaluated
      prophylactic efficacy of short-term high-dose statin pre-treatment for prevention
      of contrast-induced acute kidney injury (CIAKI) in patients undergoing coronary
      angiography (CAG). The aim of the study was to perform an up-to-date meta
      analysis regarding the efficacy of high-dose statin pre-treatment in preventing
      CIAKI. METHODS AND RESULTS: Randomized-controlled trials comparing high-dose
      statin versus low-dose statin or placebo pre-treatment for prevention of CIAKI in
      patients undergoing CAG were included. The primary endpoint was the incidence of
      CIAKI within 2-5 days after CAG. The relative risk (RR) with 95% CI was the
      effect measure. This analysis included 13 RCTs with 5,825 total patients; about
      half of them (n = 2,889) were pre-treated with high-dose statin (at least 40 mg
      of atorvastatin) before CAG, and the remainders (n = 2,936) pretreated with low
      dose statin or placebo. In random-effects model, high-dose statin pre-treatment
      significantly reduced the incidence of CIAKI (RR 0.45, 95% CI 0.35-0.57, p<0.001,
      I(2)= 8.2%, NNT 16), compared with low-dose statin or placebo. The benefit of
      high-dose statin was consistent in both comparisons with low-dose statin (RR
      0.47, 95% CI 0.34-0.65, p<0.001, I(2) = 28.4%, NNT 19) or placebo (RR 0.34, 95%
      CI 0.21-0.58, p<0.001, I(2)= 0.0%, NNT 16). In addition, high-dose statin showed
      significant reduction of CIAKI across various subgroups of chronic kidney
      disease, acute coronary syndrome, and old age (>= 60 years), regardless of
      osmolality of contrast or administration of N-acetylcystein. CONCLUSIONS: High
      dose statin pre-treatment significantly reduced overall incidence of CIAKI in
      patients undergoing CAG, and emerges as an effective prophylactic measure to
      prevent CIAKI.

PMID- 25369121
TI  - Impact of working memory load on cognitive control in trait anxiety: an ERP
      study.
AB  - Whether trait anxiety is associated with a general impairment of cognitive
      control is a matter of debate. This study investigated whether and how
      experimentally manipulated working memory (WM) load modulates the relation
      between trait anxiety and cognitive control. This question was investigated using
      a dual-task design in combination with event-related potentials. Participants
      were required to remember either one (low WM load) or six letters (high WM load)
      while performing a flanker task. Our results showed that a high WM load disrupted
      participants' ability to overcome distractor interference and this effect was
      exacerbated for the high trait-anxious (HTA) group. This exacerbation was
      reflected by larger interference effects (i.e., incongruent minus congruent) on
      reaction times (RTs) and N2 amplitudes for the HTA group than for the low trait
      anxious group under high WM load. The two groups, however, did not differ in
      their ability to inhibit task-irrelevant distractors under low WM load, as
      indicated by both RTs and N2 amplitudes. These findings underscore the
      significance of WM-related cognitive demand in contributing to the presence (or
      absence) of a general cognitive control deficit in trait anxiety. Furthermore,
      our findings show that when limited WM resources are depleted by high WM load,
      HTA individuals exhibit less efficient recruitments of cognitive control required
      for the inhibition of distractors, therefore resulting in a greater degree of
      response conflict. 

PMID- 25369122
TI  - Use of ENCODE resources to characterize novel proteoforms and missing proteins in
      the human proteome.
AB  - We describe the utility of integrated strategies that employ both translation of
      ENCODE data and major proteomic technology pillars to improve the identification
      of the "missing proteins", novel proteoforms, and PTMs. On one hand, databases in
      combination with bioinformatic tools are efficiently utilized to establish
      microarray-based transcript analysis and supply rapid protein identifications in
      clinical samples. On the other hand, sequence libraries are the foundation of
      targeted protein identification and quantification using mass spectrometric and
      immunoaffinity techniques. The results from combining proteoENCODEdb searches
      with experimental mass spectral data indicate that some alternative splicing
      forms detected at the transcript level are in fact translated to proteins. Our
      results provide a step toward the directives of the C-HPP initiative and related
      biomedical research. 

PMID- 25369123
TI  - Save water to save carbon and money: developing abatement costs for expanded
      greenhouse gas reduction portfolios.
AB  - The water-energy nexus is of growing interest for researchers and policy makers
      because the two critical resources are interdependent. Their provision and
      consumption contribute to climate change through the release of greenhouse gases
      (GHGs). This research considers the potential for conserving both energy and
      water resources by measuring the life-cycle economic efficiency of greenhouse gas
      reductions through the water loss control technologies of pressure management and
      leak management. These costs are compared to other GHG abatement technologies:
      lighting, building insulation, electricity generation, and passenger
      transportation. Each cost is calculated using a bottom-up approach where regional
      and temporal variations for three different California water utilities are
      applied to all alternatives. The costs and abatement potential for each
      technology are displayed on an environmental abatement cost curve. The results
      reveal that water loss control can reduce GHGs at lower cost than other
      technologies and well below California's expected carbon trading price floor. One
      utility with an energy-intensive water supply could abate 135,000 Mg of GHGs
      between 2014 and 2035 and save--rather than spend--more than $130/Mg using the
      water loss control strategies evaluated. Water loss control technologies
      therefore should be considered in GHG abatement portfolios for utilities and
      policy makers.

PMID- 25369124
TI  - Therapy preferences in melanoma treatment--willingness to pay and preference of
      quality versus length of life of patients, physicians and healthy controls.
AB  - BACKGROUND: New melanoma therapies, like e.g. ipilimumab, improve survival.
      However, only a small subset of patients benefits while 60% encounter side
      effects. Furthermore, these marginal benefits come at a very high price of
      ?110'000 per treatment. This study examines attitudes towards melanoma therapy
      options of physicians, healthy individuals and patients, their willingness to pay
      and preference of quality versus length of life. METHODS: Based on findings from
      a focus group questionnaires were developed and pretested. After obtaining
      ethical approval and informed consent surveys were conducted in a total of 90
      participants (n = 30 for each group). Statistical analyses were conducted using
      R. FINDINGS: Attitudes vastly differed between healthy participants, physicians
      and melanoma patients. Whereas melanoma patients show a high willingness to
      endure side effects despite very small survival gains (down to 1 extra week) or
      even only hope with no survival benefit, healthy controls are more critical,
      while physicians are the most therapy adverse. Consequently, if given ?100'000
      and the free decision what to spend the money on the willingness to pay for
      therapy was much higher in the patient group (68%) compared to 28% of healthy
      controls and only 43% of the physicians, respectively. When lowering the amount
      of cash that could be received instead of ipilimumab to ?50'000 or ?10'000 to
      test price sensitivity 69% (+1%) and 76% (+8%) of melanoma patients,
      respectively, preferred ipilimumab over cash. When judging on societal spending
      even melanoma patients opted for spending on ipilimumab in only 21%. CONCLUSION:
      The judgment about the benefits of new treatment options largely differs between
      groups, physicians being the most critical against therapy. Price elasticity was
      low.

PMID- 25369125
TI  - Glycan dependence of Galectin-3 self-association properties.
AB  - Human Galectin-3 is found in the nucleus, the cytoplasm and at the cell surface.
      This lectin is constituted of two domains: an unfolded N-terminal domain and a C
      terminal Carbohydrate Recognition Domain (CRD). There are still uncertainties
      about the relationship between the quaternary structure of Galectin-3 and its
      carbohydrate binding properties. Two types of self-association have been
      described for this lectin: a C-type self-association and a N-type self
      association. Herein, we have analyzed Galectin-3 oligomerization by Dynamic Light
      Scattering using both the recombinant CRD and the full length lectin. Our results
      proved that LNnT induces N-type self-association of full length Galectin-3.
      Moreover, from Nuclear Magnetic Resonance (NMR) and Surface Plasmon Resonance
      experiments, we observed no significant specificity or affinity variations for
      carbohydrates related to the presence of the N-terminal domain of Galectin-3. NMR
      mapping clearly established that the N-terminal domain interacts with the CRD. We
      propose that LNnT induces a release of the N-terminal domain resulting in the
      glycan-dependent self-association of Galectin-3 through N-terminal domain
      interactions. 

PMID- 25369126
TI  - Toll-like receptor responses to Peste des petits ruminants virus in goats and
      water buffalo.
AB  - Ovine rinderpest or goat plague is an economically important and contagious viral
      disease of sheep and goats, caused by the Peste des petits ruminants virus
      (PPRV). Differences in susceptibility to goat plague among different breeds and
      water buffalo exist. The host innate immune system discriminates between pathogen
      associated molecular patterns and self antigens through surveillance receptors
      known as Toll like receptors (TLR). We investigated the role of TLR and cytokines
      in differential susceptibility of goat breeds and water buffalo to PPRV. We
      examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of
      Indian domestic goats and water buffalo and demonstrated that the levels of TLR3
      and TLR7 and downstream signalling molecules correlation with susceptibility vs
      resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had
      dampened innate immune responses to PPRV and increased viral loads with lower
      basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3
      and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to
      be significantly higher while immunosuppressive interleukin (IL) 10 levels were
      lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at
      transcriptional level, correlating with reduced viralloads in infected PBMC.
      Water buffalo produced higher levels of interferon (IFN) alpha in comparison with
      goats at transcriptional and translational levels. Pre-treatment of Vero cells
      with human IFNalpha resulted in reduction of PPRV replication, confirming the
      role of IFNalpha in limiting PPRV replication. Treatment with IRS66, a TLR7
      antagonist, resulted in the reduction of IFNalpha levels, with increased PPRV
      replication confirming the role of TLR7. Single nucleotide polymorphism analysis
      of TLR7 of these goat breeds did not show any marked nucleotide differences that
      might account for susceptibility vs resistance to PPRV. Analyzing other host
      genetic factors might provide further insights on susceptibility to PPRV and
      genetic polymorphisms in the host. 

PMID- 25369127
TI  - Group 9 organometallic compounds for therapeutic and bioanalytical applications.
AB  - CONSPECTUS: Compared with organic small molecules, metal complexes offer several
      distinct advantages as therapeutic agents or biomolecular probes. Carbon atoms
      are typically limited to linear, trigonal planar, or tetrahedral geometries, with
      a maximum of two enantiomers being formed if four different substituents are
      attached to a single carbon. In contrast, an octahedral metal center with six
      different substituents can display up to 30 different stereoisomers. While
      platinum- and ruthenium-based anticancer agents have attracted significant
      attention in the realm of inorganic medicinal chemistry over the past few
      decades, group 9 complexes (i.e., iridium and rhodium) have garnered increased
      attention in therapeutic and bioanalytical applications due to their adjustable
      reactivity (from kinetically liable to substitutionally inert), high water
      solubility, stability to air and moisture, and relative ease of synthesis. In
      this Account, we describe our efforts in the development of group 9
      organometallic compounds of general form [M(C(?)N)2(N(?)N)] (where M = Ir, Rh) as
      therapeutic agents against distinct biomolecular targets and as luminescent
      probes for the construction of oligonucleotide-based assays for a diverse range
      of analytes. Earlier studies by researchers had focused on organometallic
      iridium(III) and rhodium(III) half-sandwich complexes that show promising
      anticancer activity, although their precise mechanisms of action still remain
      unknown. More recently, kinetically-inert group 9 complexes have arisen as
      fascinating alternatives to organic small molecules for the specific targeting of
      enzyme activity. Research in our laboratory has shown that cyclometalated
      octahedral rhodium(III) complexes were active against Janus kinase 2 (JAK2) or
      NEDD8-activating enzyme (NAE) activity, or against NO production leading to
      antivasculogenic activity in cellulo. At the same time, recent interest in the
      development of small molecules as modulators of protein-protein interactions has
      stimulated our research group to investigate whether kinetically-inert metal
      complexes could also be used to target protein-protein interfaces relevant to the
      pathogenesis of certain diseases. We have recently discovered that cyclometalated
      octahedral iridium(III) and rhodium(III) complexes bearing C(?)N ligands based on
      2-phenylpyridine could function as modulators of protein-protein interactions,
      such as TNF-alpha, STAT3, and mTOR. One rhodium(III) complex antagonized STAT3
      activity in vitro and in vivo and displayed potent antitumor activity in a mouse
      xenograft model of melanoma. Notably, these studies were among the first to
      demonstrate the direct inhibition of protein-protein interfaces by kinetically
      inert group 9 metal complexes. Additionally, we have discovered that group 9
      solvato complexes carrying 2-phenylpyridine coligands could function as
      inhibitors and probes of beta-amyloid fibrillogenesis. Meanwhile, the rich
      photophysical properties of iridium complexes have made them popular tools for
      the design of luminescent labels and probes. Luminescent iridium(III) complexes
      benefit from a high quantum yield, responsive emissive properties, long-lived
      phosphorescence lifetimes, and large Stokes shift values. Over the past few
      years, our group has developed a number of kinetically-inert, organometallic
      iridium(III) complexes bearing various C(?)N and N(?)N ligands that are selective
      for G-quadruplex DNA, which is a DNA secondary structure formed from planar
      stacks of guanine tetrads stabilized by Hoogsteen hydrogen bonding. These
      complexes were then employed to develop G-quadruplex-based, label-free
      luminescence switch-on assays for nucleic acids, enzyme activity, small
      molecules, and metal ions.

PMID- 25369128
TI  - New insights into phosphorus mobilisation from sulphur-rich sediments: time
      dependent effects of salinisation.
AB  - Internal phosphorus (P) mobilisation from aquatic sediments is an important
      process adding to eutrophication problems in wetlands. Salinisation, a fast
      growing global problem, is thought to affect P behaviour. Although several
      studies have addressed the effects of salinisation, interactions between salinity
      changes and nutrient cycling in freshwater systems are not fully understood. To
      tackle eutrophication, a clear understanding of the interacting effects of
      sediment characteristics and surface water quality is vital. In the present
      study, P release from two eutrophic sediments, both characterized by high pore
      water P and very low pore water iron (Fe(2+)) concentrations, was studied in a
      long-term aquarium experiment, using three salinity levels. Sediment P release
      was expected to be mainly driven by diffusion, due to the eutrophic conditions
      and low iron availability. Unexpectedly, this only seemed to be the driving
      mechanism in the short term (0-10 weeks). In the long term (>80 weeks), P
      mobilisation was absent in most treatments. This can most likely be explained by
      the oxidation of the sediment-water interface where Fe(2+) immobilises P, even
      though it is commonly assumed that free Fe(2+) concentrations need to be higher
      for this. Therefore, a controlling mechanism is suggested in which the partial
      oxidation of iron-sulphides in the sediment plays a key role, releasing extra
      Fe(2+) at the sediment-water interface. Although salinisation was shown to lower
      short-term P mobilisation as a result of increased calcium concentrations, it may
      increase long-term P mobilisation by the interactions between sulphate reduction
      and oxygen availability. Our study showed time-dependent responses of sediment P
      mobilisation in relation to salinity, suggesting that sulphur plays an important
      role in the release of P from FeSx-rich sediments, its biogeochemical effect
      depending on the availability of Fe(2+) and O2.

PMID- 25369130
TI  - Diagnostic overshadowing and other challenges involved in the diagnostic process
      of patients with mental illness who present in emergency departments with
      physical symptoms--a qualitative study.
AB  - We conducted a qualitative study in the Emergency Departments (EDs) of four
      hospitals in order to investigate the perceived scope and causes of 'diagnostic
      overshadowing'--the misattribution of physical symptoms to mental illness--and
      other challenges involved in the diagnostic process of people with mental illness
      who present in EDs with physical symptoms. Eighteen doctors and twenty-one nurses
      working in EDs and psychiatric liaisons teams in four general hospitals in the UK
      were interviewed. Interviewees were asked about cases in which mental illness
      interfered with diagnosis of physical problems and about other aspects of the
      diagnostic process. Interviews were transcribed and analysed thematically.
      Interviewees reported various scenarios in which mental illness or factors
      related to it led to misdiagnosis or delayed treatment with various degrees of
      seriousness. Direct factors which may lead to misattribution in this regard are
      complex presentations or aspects related to poor communication or challenging
      behaviour of the patient. Background factors are the crowded nature of the ED
      environment, time pressures and targets and stigmatising attitudes held by a
      minority of staff. The existence of psychiatric liaison team covering the ED
      twenty-four hours a day, seven days a week, can help reduce the risk of
      misdiagnosis of people with mental illness who present with physical symptoms.
      However, procedures used by emergency and psychiatric liaison staff require
      fuller operationalization to reduce disagreement over where responsibilities lie.

PMID- 25369131
TI  - Enhanced cellular uptake of albumin-based lyophilisomes when functionalized with
      cell-penetrating peptide TAT in HeLa cells.
AB  - Lyophilisomes are a novel class of biodegradable proteinaceous nano/micrometer
      capsules with potential use as drug delivery carrier. Cell-penetrating peptides
      (CPPs) including the TAT peptide have been successfully implemented for
      intracellular delivery of a broad variety of cargos including various
      nanoparticulate pharmaceutical carriers. In the present study, lyophilisomes were
      modified using CPPs in order to achieve enhanced cellular uptake. Lyophilisomes
      were prepared by a freezing, annealing, and lyophilization method and a cystein
      elongated TAT peptide was conjugated to the lyophilisomes using a
      heterobifunctional linker. Fluorescent-activated cell sorting (FACS) was utilized
      to acquire a lyophilisome population with a particle diameter smaller than 1000
      nm. Cultured HeLa, OVCAR-3, Caco-2 and SKOV-3 cells were exposed to unmodified
      lyophilisomes and TAT-conjugated lyophilisomes and examined with FACS. HeLa cells
      were investigated in more detail using a trypan blue quenching assay, confocal
      microscopy, and transmission electron microscopy. TAT-conjugation strongly
      increased binding and cellular uptake of lyophilisomes in a time-dependent manner
      in vitro, as assessed by FACS. These results were confirmed by confocal
      microscopy. Transmission electron microscopy indicated rapid cellular uptake of
      TAT-conjugated lyophilisomes via phagocytosis and/or macropinocytosis. In
      conclusion, TAT-peptides conjugated to albumin-based lyophilisomes are able to
      enhance cellular uptake of lyophilisomes in HeLa cells. 

PMID- 25369132
TI  - Chalcones from Angelica keiskei attenuate the inflammatory responses by
      suppressing nuclear translocation of NF-kappaB.
AB  - The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei
      showed potent inhibitory activity against the production of nitric oxide (NO) in
      lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones
      (1-7) from EtOAc-soluble fractions through the activity-guided separation. Four
      active principles, identified as 4-hydroxyderrcine (1), xanthoangelol E (2),
      xanthokeismin A (4), and xanthoangelol B (5), inhibited the production of NO and
      the expression of proinflammatory cytokines, interleukin (IL)-1beta and IL-6, in
      LPS-activated macrophages. Western blotting and reverse transcription-polymerase
      chain reaction analysis demonstrated that these chalcones attenuated protein and
      mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed
      the degradation of inhibitory-kappaBalpha (I-kappaBalpha) and the translocation
      of nuclear factor kappaB (NF-kappaB) into nuclei of LPS-activated macrophages.
      These data demonstrate that four chalcones (1, 2, 4, and 5) from A. keiskei can
      suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes
      by inhibiting the degradation of I-kappaBalpha and nuclear translocation of NF
      kappaB. Taken together, four chalcones from A. keiskei may have efficacy as anti
      inflammatory agents.

PMID- 25369134
TI  - Hemodynamic management of septic shock.
AB  - We present a review of the hemodynamic management of septic shock. Although
      substantial amount of evidence is present in this area, most key decisions on the
      management of these patients remain dependent on physiological reasoning and on
      pathophysiological principles rather than randomized controlled trials. During
      primary (early) resuscitation, restoration of adequate arterial pressure and
      cardiac output using fluids and vasopressor and/or inotropic drugs is guided by
      basic hemodynamic monitoring and physical examination in the emergency
      department. When more advanced level of monitoring is present in these patients,
      i.e. during secondary resuscitation (later phase in the emergency department and
      in the ICU), hemodynamic management can be guided by more advanced measurements
      of the macrocirculation. Our understanding of the microcirculation in septic
      shock is limited and reliable therapeutic modalities to optimize it do not yet
      exist. No specific hemodynamic treatment strategy, be it medications including
      fluids, monitoring devices or treatment algorithms has yet been proved to improve
      outcome. Moreover, there is virtually no data on the optimal management of the
      resolution phase of septic shock. Despite these gaps in knowledge, the data from
      observational studies and trials suggests that mortality in septic shock has been
      generally decreasing during the last decade. 

PMID- 25369133
TI  - "Glowing head" mice: a genetic tool enabling reliable preclinical image-based
      evaluation of cancers in immunocompetent allografts.
AB  - Preclinical therapeutic assessment currently relies on the growth response of
      established human cell lines xenografted into immunocompromised mice, a strategy
      that is generally not predictive of clinical outcomes. Immunocompetent
      genetically engineered mouse (GEM)-derived tumor allograft models offer highly
      tractable preclinical alternatives and facilitate analysis of clinically
      promising immunomodulatory agents. Imageable reporters are essential for
      accurately tracking tumor growth and response, particularly for metastases.
      Unfortunately, reporters such as luciferase and GFP are foreign antigens in
      immunocompetent mice, potentially hindering tumor growth and confounding
      therapeutic responses. Here we assessed the value of reporter-tolerized GEMs as
      allograft recipients by targeting minimal expression of a luciferase-GFP fusion
      reporter to the anterior pituitary gland (dubbed the "Glowing Head" or GH mouse).
      The luciferase-GFP reporter expressed in tumor cells induced adverse immune
      responses in wildtype mouse, but not in GH mouse, as transplantation hosts. The
      antigenicity of optical reporters resulted in a decrease in both the growth and
      metastatic potential of the labeled tumor in wildtype mice as compared to the GH
      mice. Moreover, reporter expression can also alter the tumor response to
      chemotherapy or targeted therapy in a context-dependent manner. Thus the GH mice
      and experimental approaches vetted herein provide concept validation and a
      strategy for effective, reproducible preclinical evaluation of growth and
      response kinetics for traceable tumors. 

PMID- 25369135
TI  - Treating mass effect from aneurysmal rupture: is early surgery the answer?

PMID- 25369136
TI  - The need for an international standardized guideline regarding pediatric delirium
      -Reply to the letter by Giusti et al.

PMID- 25369137
TI  - A multilocus genetic study in a cohort of Italian SLE patients confirms the
      association with STAT4 gene and describes a new association with HCP5 gene.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with
      complex pathogenesis in which genes and environmental factors are involved. We
      aimed at analyzing previously identified loci associated with SLE or with other
      autoimmune and/or inflammatory disorders (STAT4, IL10, IL23R, IRAK1, PSORS1C1,
      HCP5, MIR146a, PTPN2, ERAP1, ATG16L1, IRGM) in a sample of Italian SLE patients
      in order to verify or confirm their possible involvement and relative
      contribution in the disease. MATERIALS AND METHODS: Two hundred thirty-nine
      consecutive SLE patients and 278 matched healthy controls were enrolled. Study
      protocol included complete physical examination, and clinical and laboratory data
      collection. Nineteen polymorphisms were genotyped by allelic discrimination
      assays. A case-control association study and a genotype-phenotype correlation
      were performed. RESULTS: STAT4 was the most associated gene [P = 3 * 10(-7), OR =
      2.13 (95% CI: 1.59-2.85)]. IL10 confirmed its association with SLE [rs3024505: P
      = 0.02, OR = 1.52 (95% CI: 1.07-2.16)]. We describe a novel significant
      association between HCP5 locus and SLE susceptibility [rs3099844: P = 0.01, OR =
      2.06 (95% CI: 1.18-3.6)]. The genotype/phenotype correlation analysis showed
      several associations including a higher risk to develop pericarditis with STAT4,
      and an association between HCP5 rs3099844 and anti-Ro/SSA antibodies.
      CONCLUSIONS: STAT4 and IL10 confirm their association with SLE. We found that
      some SNPs in PSORS1C1, ATG16L1, IL23R, PTPN2 and MIR146a genes can determine
      particular disease phenotypes. HCP5 rs3099844 is associated with SLE and with
      anti-Ro/SSA. This polymorphism has been previously found associated with cardiac
      manifestations of SLE, a condition related with anti-Ro/SSA antibodies. Thus, our
      results may provide new insights into SLE pathogenesis.

PMID- 25369138
TI  - Predictability of extreme events in social media.
AB  - It is part of our daily social-media experience that seemingly ordinary items
      (videos, news, publications, etc.) unexpectedly gain an enormous amount of
      attention. Here we investigate how unexpected these extreme events are. We
      propose a method that, given some information on the items, quantifies the
      predictability of events, i.e., the potential of identifying in advance the most
      successful items. Applying this method to different data, ranging from views in
      YouTube videos to posts in Usenet discussion groups, we invariantly find that the
      predictability increases for the most extreme events. This indicates that,
      despite the inherently stochastic collective dynamics of users, efficient
      prediction is possible for the most successful items. 

PMID- 25369139
TI  - Electrophoretic migration and particle collisions in scanning electrochemical
      microscopy.
AB  - We report for the first time how electrophoretic migration of ions and charged
      nanoparticles (NPs) in low electrolyte concentration solutions affects positive
      feedback in scanning electrochemical microscopy (SECM). The strength of the
      electric field in the gap between either the tip and the substrate, or the tip
      and counter electrodes, is shown to increase proportionally to the decrease in
      gap size. This field affects the flux of the charged redox species as expected
      for dilute electrolyte solutions. However, the shape of the normalized approach
      curve is unaffected by the electrophoretic migration. We also report that the
      rate of collisions of charged insulating NPs with the tip electrode decreases as
      the tip is brought closer to the substrate electrode. This rather unexpected
      result (negative feedback) can be explained by the blocking of the particle flux
      with the glass insulating layer around the metal microwires. Observation of
      simultaneous changes in the faradaic current at the tip and substrate electrodes
      due to particle collisions with the tip confirms a high rate of mass transport
      between the two electrodes under the conditions of positive feedback SECM. 

PMID- 25369141
TI  - Efficacy and safety of metformin for patients with type 1 diabetes mellitus: a
      meta-analysis.
AB  - BACKGROUND: Insulin is an essential therapy for patients with type 1 diabetes
      mellitus (T1DM). With the progression of the disease, many patients with T1DM may
      have an increased prevalence of insulin resistance; thus the common standard
      insulin therapy requires a high insulin dosage (>1 unit/kg/day) and is usually
      associated with many side effects. Studies have shown that metformin may benefit
      those insulin-resistant individuals with T1DM. This meta-analysis was performed
      to provide the evidence of clinical efficacy and safety of metformin in T1DM.
      MATERIALS AND METHODS: We conducted a search on Medline, EMBASE, and the Cochrane
      Library for relevant studies published before May 2014 based on "metformin" and
      "diabetes mellitus, type 1." The following outcomes were evaluated: hemoglobin
      A1c (HbA1c), fasting plasma glucose (FPG), lipid metabolism, weight, insulin
      dosage, hypoglycemia, diabetic ketoacidosis, or gastrointestinal adverse events
      (AEs). The meta-analysis was performed using Review Manager version 5.2 software
      (The Nordic Cochrane Centre, Copenhagen, Denmark). RESULTS: In total, eight
      randomized controlled trials were included. Metformin was associated with a
      reduction in daily insulin dosage, body weight, total cholesterol level, low
      density lipoprotein level, and high-density lipoprotein level but an increase in
      risk of gastrointestinal AEs compared with placebo treatment in T1DM patients. No
      significant difference was found between the metformin group and the placebo
      group in HbA1c level, FPG level, or triglycerides level. No significant
      difference was found between the metformin group and the placebo group in the
      risk of severe hypoglycemia or diabetic ketoacidosis. CONCLUSIONS: Metformin may
      decrease the daily insulin dosage, body weight, and lipid levels in T1DM.
      However, metformin does not increase the incidence of hypoglycemia and
      ketoacidosis. High-quality, large-sample, and long-term follow-up clinical trials
      are needed to confirm these conclusions.

PMID- 25369140
TI  - Oral administration of nano-emulsion curcumin in mice suppresses inflammatory
      induced NFkappaB signaling and macrophage migration.
AB  - Despite the widespread use of curcumin for centuries in Eastern medicine as an
      anti-inflammatory agent, its molecular actions and therapeutic viability have
      only recently been explored. While curcumin does have potential therapeutic
      efficacy, both solubility and bioavailability must be improved before it can be
      more successfully translated to clinical care. We have previously reported a
      novel formulation of nano-emulsion curcumin (NEC) that achieves significantly
      greater plasma concentrations in mice after oral administration. Here, we confirm
      the immunosuppressive effects of NEC in vivo and further examine its molecular
      mechanisms to better understand therapeutic potential. Using transgenic mice
      harboring an NFkappaB-luciferase reporter gene, we demonstrate a novel
      application of this in vivo inflammatory model to test the efficacy of NEC
      administration by bioluminescent imaging and show that LPS-induced NFkappaB
      activity was suppressed with NEC compared to an equivalent amount of curcumin in
      aqueous suspension. Administration of NEC by oral gavage resulted in a reduction
      of blood monocytes, decreased levels of both TLR4 and RAGE expression, and
      inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced
      phosphorylation of the p65 subunit of NFkappaB and IkappaBalpha in murine
      macrophages. In a mouse model of peritonitis, NEC significantly reduced
      macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin
      treatment of monocyte derived cell lines and primary human macrophages in vitro
      significantly inhibited cell migration. These data demonstrate that curcumin can
      suppress inflammation by inhibiting macrophage migration via NFkappaB and MCP-1
      inhibition and establish that NEC is an effective therapeutic formulation to
      increase the bioavailability of curcumin in order to facilitate this response. 

PMID- 25369144
TI  - Quantitative proteomics of delirium cerebrospinal fluid.
AB  - Delirium is a common cause and complication of hospitalization in older people,
      being associated with higher risk of future dementia and progression of existing
      dementia. However relatively little data are available on which biochemical
      pathways are dysregulated in the brain during delirium episodes, whether there
      are protein expression changes common among delirium subjects and whether there
      are any changes which correlate with the severity of delirium. We now present the
      first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few
      studies exploring protein expression changes in delirium. More than 270 proteins
      were identified in two delirium cohorts, 16 of which were dysregulated in at
      least 8 of 17 delirium subjects compared with a mild Alzheimer's disease
      neurological control group, and 31 proteins were significantly correlated with
      cognitive scores (mini-mental state exam and acute physiology and chronic health
      evaluation III). Bioinformatics analyses revealed expression changes in several
      protein family groups, including apolipoproteins, secretogranins/chromogranins,
      clotting/fibrinolysis factors, serine protease inhibitors and acute-phase
      response elements. These data not only provide confirmatory evidence that the
      inflammatory response is a component of delirium, but also reveal dysregulation
      of protein expression in a number of novel and unexpected clusters of proteins,
      in particular the granins. Another surprising outcome of this work is the level
      of similarity of CSF protein profiles in delirium patients, given the diversity
      of causes of this syndrome. These data provide additional elements for
      consideration in the pathophysiology of delirium as well as potential biomarker
      candidates for delirium diagnosis. 

PMID- 25369145
TI  - Identifying individual differences of fluoxetine response in juvenile rhesus
      monkeys by metabolite profiling.
AB  - Fluoxetine is the only psychopharmacological agent approved for depression by the
      US Food and Drug Administration for children and is commonly used therapeutically
      in a variety of neurodevelopmental disorders. Therapeutic response shows high
      individual variability, and severe side effects have been observed. In the
      current study we set out to identify biomarkers of response to fluoxetine as well
      as biomarkers that correlate with impulsivity, a measure of reward delay behavior
      and potential side effect of the drug, in juvenile male rhesus monkeys. The study
      group was also genotyped for polymorphisms of monoamine oxidase A (MAOA), a gene
      that has been associated with psychiatric disorders. We used peripheral
      metabolite profiling of blood and cerebrospinal fluid (CSF) from animals treated
      daily with fluoxetine or vehicle for one year. Fluoxetine response metabolite
      profiles and metabolite/reward delay behavior associations were evaluated using
      multivariate analysis. Our analyses identified a set of plasma and CSF
      metabolites that distinguish fluoxetine- from vehicle-treated animals and
      metabolites that correlate with impulsivity. Some metabolites displayed an
      interaction between fluoxetine and MAOA genotype. The identified metabolite
      biomarkers belong to pathways that have important functions in central nervous
      system physiology. Biomarkers of response to fluoxetine in the normally
      functioning brain of juvenile nonhuman primates may aid in finding predictors of
      response to treatment in young psychiatric populations and in progress toward the
      realization of a precision medicine approach in the area of neurodevelopmental
      disorders. 

PMID- 25369146
TI  - Bioaccumulation of heavy metals in blood and tissue of striped mullet in two
      Italian lakes.
AB  - Water and sediment from Faro and Ganzirri lakes were tested for cadmium, mercury,
      and lead. These heavy metals have been assessed in serum and muscles of Striped
      Mullet Mugil cephalus. A haemogram was performed to find effects of heavy metals
      on haematological variables. Student's t-test showed higher Pb levels in
      sediments of Ganzirri Lake than Faro Lake. Two-way analysis of variance showed
      higher Cd and Pb concentration in muscles samples of Striped Mullet from Ganzirri
      Lake than from Faro Lake. Significant differences were found among haematological
      parameters as well. Mullet from Ganzirri Lake had lower white and red blood cell
      and trombocyte counts and higher mean corpuscular haemoglobin and mean
      corpuscular haemoglobin concentration than those from Faro Lake. Our results
      indicate a significant presence of lead in the environmental produces an
      accumulation of this metal in fish muscles.

PMID- 25369147
TI  - Age-related association of refractive error with intraocular pressure in the
      Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND: To investigate the distribution of intraocular pressure (IOP) and
      refractive errors according to age group in a representative sample of non
      glaucomatous Korean adults. METHODS: A total of 7,277 adults (>= 19 years) who
      participated in the Korea National Health and Nutrition Examination Survey
      (KNHANES) from 2008 to 2011 underwent ophthalmic examination were divided into
      three groups according to age: the young- (19-39 years), middle- (40-59 years),
      and old- (>= 60 years) age groups. Simple and multiple regression analyses
      between IOP and various parameters (including the refractive error) were
      conducted. RESULTS: The mean IOP of the total population was 14.0 +/- 0.1 mmHg
      [young: 13.9 +/- 0.1 mmHg; middle: 14.1 +/- 0.1 mmHg; old: 13.8 +/- 0.2 mmHg (P
      for trend = 0.085)]. Myopia and high myopia were more prevalent in the young-
      (70.8% and 16.1%, respectively), compared to the middle- (44.6% and 10.9%) and
      old- (8.9% and 2.2%) age groups. Univariate analysis in the total population
      showed that higher IOP was associated with myopic refractive error, the female
      gender, higher body mass index (BMI), diabetes, hypertension, and
      hypercholesterolemia (all P<0.05). In the young- and middle-age groups, higher
      IOP was associated with myopic refractive error, the female gender, higher BMI,
      hypercholesterolemia and diabetes (all P<0.05). In the old-age group, the
      association between IOP and refractive error was not significant (P = 0.828). In
      multiple linear regression analysis, similar significant relationships between
      the refractive error and IOP were found in the young- and middle-age groups (beta
      =  -0.08 and -0.12; P = 0.002 and <0.001 for young- and middle-age group,
      respectively), but not in the old-age group (beta = 0.03; P = 0.728), after
      adjusting for age, gender, BMI, region of habitation, diabetes, hypertension, and
      hypercholesterolemia. CONCLUSIONS: Myopic refractive error was an independent
      predictor of higher IOP in non- glaucomatous eyes, and the association between
      refractive error and IOP differed according to age.

PMID- 25369148
TI  - The effect of surgical titanium rods on proton therapy delivered for cervical
      bone tumors: experimental validation using an anthropomorphic phantom.
AB  - To investigate the effect of metal implants in proton radiotherapy, dose
      distributions of different, clinically relevant treatment plans have been
      measured in an anthropomorphic phantom and compared to treatment planning
      predictions. The anthropomorphic phantom, which is sliced into four segments in
      the cranio-caudal direction, is composed of tissue equivalent materials and
      contains a titanium implant in a vertebral body in the cervical region.
      GafChromic(r) films were laid between the different segments to measure the 2D
      delivered dose. Three different four-field plans have then been applied: a Single
      Field-Uniform-Dose (SFUD) plan, both with and without artifact correction
      implemented, and an Intensity-Modulated-Proton-Therapy (IMPT) plan with the
      artifacts corrected. For corrections, the artifacts were manually outlined and
      the Hounsfield Units manually set to an average value for soft tissue. Results
      show a surprisingly good agreement between prescribed and delivered dose
      distributions when artifacts have been corrected, with > 97% and 98% of points
      fulfilling the gamma criterion of 3%/3 mm for both SFUD and the IMPT plans,
      respectively. In contrast, without artifact corrections, up to 18% of measured
      points fail the gamma criterion of 3%/3 mm for the SFUD plan. These measurements
      indicate that correcting manually for the reconstruction artifacts resulting from
      metal implants substantially improves the accuracy of the calculated dose
      distribution.

PMID- 25369149
TI  - Cholecalciferol synthesized after UV-activation of 7-dehydrocholesterol onto
      titanium implants inhibits osteoclastogenesis in vitro.
AB  - UV-activated 7-dehydrocholesterol (7-DHC) has been successfully used as a
      biocompatible coating for titanium (Ti) implants producing active vitamin D with
      positive effect on osteoblast differentiation. Since an osseointegrating implant
      must promote bone formation while delay resorption, here we determine the effect
      of this coating on the pre-osteoclast cell line RAW 264.7. Moreover, D3 synthesis
      was optimized by (1) the supplementation with VitE of the 7-DHC coating to reduce
      7-DHC oxidation and (2) the addition of an incubation step (48 h at 23 degrees C)
      after UV-irradiation to favor isomerization. In vitro results with RAW264.7 cells
      showed no cytotoxic effect of the coatings and a significant decrease of
      osteoclastogenesis. Indeed, TRAP immunostaining suggested an inhibition of Trap
      positive multinucleated cells and the mRNA levels of different phenotypic,
      fusion, and activity markers were reduced, particularly with 7-DHC:VitE. In
      conclusion, we demonstrate an improvement of the D3 synthesis from UV-activated 7
      DHC when combined with VitE and show that these implants inhibit
      osteoclastogenesis in vitro.

PMID- 25369150
TI  - Patterns of locoregional treatment for nonmetastatic breast cancer by patient and
      health system factors.
AB  - BACKGROUND: The purpose of this study was to examine local definitive therapy for
      nonmetastatic breast cancer with the Patterns of Care Breast and Prostate Cancer
      (POCBP) study of the National Program of Cancer Registries (Centers for Disease
      Control and Prevention). METHODS: POCBP medical record data were re-abstracted in
      7 state/regional registry systems (Georgia, North Carolina, Kentucky, Louisiana,
      Wisconsin, Minnesota, and California) to verify data quality and assess treatment
      patterns in the population. National Comprehensive Cancer Network clinical
      practice treatment guidelines were aligned with American Joint Committee on
      Cancer staging at diagnosis to appraise care. RESULTS: Six thousand five hundred
      five of 9142 patients with registry-confirmed breast cancer were coded as having
      primary disease with stage 0 to IIIA tumors and were included in the study.
      Approximately 88% received guideline-concordant locoregional treatment. However,
      this outcome varied by age group: 92% of women < age 50 versus 80% of women >=
      age 70 years old received guideline care (P < 0.01). Characteristics that best
      discriminated receipt (no/yes) of guideline-concordant care in receiver operating
      curve analyses were the receipt of breast-conserving surgery (BCS) versus
      mastectomy (C = 0.70), patient age (C = 0.62), a greater tumor stage (C = 0.60),
      public insurance (C = 0.58), and the presence of at least mild comorbidity (C =
      0.55). Radiation therapy (RT) after BCS was the most omitted treatment component
      causing nonconcordance in the study population. In multivariate regression, the
      effects of the treatment facility, ductal carcinoma in situ, race, and
      comorbidity on nonconcordant care differed by age group. CONCLUSIONS: Patterns of
      underuse of standard therapies for breast cancer vary by age group and BCS use,
      with which there is a risk of omission of RT.

PMID- 25369151
TI  - Unusual aerobic stabilization of Cob(I)alamin by a B12-trafficking protein allows
      chemoenzymatic synthesis of organocobalamins.
AB  - CblC, a B12 trafficking protein, exhibits glutathione transferase and reductive
      decyanase activities for processing alkylcobalamins and cyanocobalamin,
      respectively, to a common intermediate that is subsequently converted to the
      biologically active forms of the cofactor. We recently discovered that the
      Caenorhabditis elegans CblC catalyzes thiol-dependent decyanation of CNCbl and
      reduction of OH2Cbl and stabilizes the paramagnetic cob(II)alamin product under
      aerobic conditions. In this study, we report the striking ability of the worm
      CblC to stabilize the highly reactive cob(I)alamin product of the glutathione
      transferase reaction. The unprecedented stabilization of the supernucleophilic
      cob(I)alamin species under aerobic conditions by the intrinsic thiol oxidase
      activity of CblC, was exploited for the chemoenzymatic synthesis of
      organocobalamin derivatives under mild conditions. 

PMID- 25369153
TI  - Quasi-in-situ single-grain photoelectron microspectroscopy of Co/PPy
      nanocomposites under oxygen reduction reaction.
AB  - This paper reports an investigation into the aging of pyrolyzed
      cobalt/polypyrrole (Co/PPy) oxygen reduction reaction (ORR) electrocatalysts,
      based on quasi-in-situ photoelectron microspectroscopy. The catalyst precursor
      was prepared by potentiostatic reverse-pulse coelectrodeposition from an
      acetonitrile solution on graphite. Accelerated aging was obtained by quasi-in
      situ voltammetric cycling in an acidic electrolyte. Using photoelectron imaging
      and microspectroscopy of single Co/PPy grains at a resolution of 100 nm, we
      tracked the ORR-induced changes in the morphology and chemical state of the
      pristine material, consisting of uniformly distributed ~20 nm nanoparticles,
      initially consisting of a mixture of Co(II) and Co(III) oxidation states in
      almost equal amounts. The evolution of the Co 2p, O 1s, and N 1s spectra revealed
      that the main effects of aging are a gradual loss of the Co present at the
      surface and the reduction of Co(III) to Co(II), accompanied by the emergence and
      growth of a N 1s signal, corresponding to electrocatalytically active C-N sites. 

PMID- 25369152
TI  - Optic nerve sheath diameter remains constant during robot assisted laparoscopic
      radical prostatectomy.
AB  - BACKGROUND: During robot assisted laparoscopic radical prostatectomy (RALRP), a
      CO2 pneumoperitoneum (CO2PP) is applied and the patient is placed in a head-down
      position. Intracranial pressure (ICP) is expected to acutely increase under these
      conditions. A non-invasive method, the optic nerve sheath diameter (ONSD)
      measurement, may warn us that the mechanism of protective cerebrospinal fluid
      (CSF) shifts becomes exhausted. METHODS: After obtaining IRB approval and written
      informed consent, ONSD was measured by ocular ultrasound in 20 ASA I-II patients
      at various stages of the RALRP procedure: baseline awake, after induction, after
      applying the CO2PP, during head-down position, after resuming the supine
      position, in the postoperative anaesthesia care unit, and on day one
      postoperatively. Cerebral perfusion pressure (CPP) was calculated as the mean
      arterial (MAP) minus central venous pressure (CVP). RESULTS: The ONSD did not
      change during head-down position, although the CVP increased from 4.2(2.5) mm Hg
      to 27.6(3.8) mm Hg. The CPP was decreased 70 min after assuming the head-down
      position until 15 min after resuming the supine position, but remained above 60
      mm Hg at all times. CONCLUSION: Even though ICP has been documented to increase
      during CO2PP and head-down positioning, we did not find any changes in ONSD
      during head-down position. These results indicate that intracranial blood volume
      does not increase up to a point that CSF migration as a compensation mechanism
      becomes exhausted, suggesting any increases in ICP are likely to be small.

PMID- 25369154
TI  - [Editor's comment. This issue is dedicated to Professor Gerhard Rettinger].

PMID- 25369155
TI  - [Editorial. The current "Festschrift" is dedicated to Prof. Dr. h. c. Gerhard
      Rettinger].

PMID- 25369156
TI  - [The Oticum cum Dignitate].

PMID- 25369157
TI  - [Test using vapourated expired nasal breathing in medicine 100 years ago and in
      paestum 2 300 years ago].
AB  - This historical sketch follows the traces of a mirror, once used to test the last
      breath of a dying woman. It was found on the fresco of a tomb in Paestum dated
      about 320 BC. In 1889, Hendrik Zwaardemaker (Utrecht) was the first to present a
      hygrometric functional test using a cold mirror placed under the nose to estimate
      the degree of airflow obstruction during exhalation. In 1901, Ernst Glatzel
      (Berlin) modified Zwaardemaker's concept by engraving a series of equidistant
      arcs into his metallic mirror to further quantify the amounts of condensed vapour
      in the expired air. The Glatzel-mirror was used in Germany until after the Second
      World War. 

PMID- 25369158
TI  - [Sneezing as a mechanical defence - a numerical simulation and analysis of the
      nasal flow].
AB  - INTRODUCTION: The nose is responsible for humidification, heating and cleaning of
      the inhaled air. The sneeze reflex leads to a shock-like cleaning of the nose in
      strong particle exposure. The aim of this study was the simulation of intranasal
      air flow of sneezing in a realistic computer model. MATERIALS AND METHODS: Based
      on the CT scan of a 40 year old man a three-dimensional computer model of the
      nasal cavity and the ethmoid sinuses was created. Flow simulations were performed
      for different inspiratory and expiratory velocities (+/- 2 m/s to +/- 45 m/s) in
      order to simulate sneezing. RESULTS were visualized and analyzed by video
      simulation. RESULTS: During inspiration the main airflow takes place along the
      middle turbinate. During expiration, the flow is located more cranially. This
      effect is caused by the shape of the nasopharynx and the posterior portions of
      the nasal turbinates. During very high speeds (sneezing) also adjacent ethmoid
      sinuses and the olfactory region are covered by the shock-like expiratory flow. A
      large vortex formation in the nasopharynx is responsible for a uniform
      distribution of the airflow also on lower nasal areas. CONCLUSION: Sneezing is a
      protective reflex that provides for cleaning of the nose. From a flow rate of 10
      m/s, the cranial nasal areas as well as adjacent ethmoid sinuses are covered by
      the -airflow. Compared to the inspiratory airflow the exhalation is not just vice
      versa. Particles that deposed in the cranial nasal areas during quiet breathing
      are removed.

PMID- 25369159
TI  - [Long-term results after surgical closures of septal perforations].
AB  - OBJECTIVE: The surgical closure of a nasal septal perforation (SP) is a
      technically difficult operation, which requires a great deal of experience of the
      surgeon. Amazingly, the success rate in the literature is given as about 90%. In
      these studies, the retrospective follow up is generally very short. Therefore,
      the aim of this study was to examine the late results of surgical closures of SP
      in a combined prospective, consecutive observational study. Material und Methods:
      From 2000 to 2010 a total of 348 patients received a surgical closure of a SP by
      using bridge flaps, open / closed approach, with / without interposition of ear
      cartilage. 200 patients were included. In 187 patients a complete closure has
      been planned. 109 (58%) had undergone previous nose surgery. The median follow-up
      between surgery and last examination was 67 months (12 to 144). RESULTS: A long
      term closure of the SP was achieved in 72% (n=134). In 28% (n=53) a recurrence
      occurred. In 13 patients, only a partial closure based on the size of the SP was
      carried out. Factors influencing success rates as well as the current literature
      are discussed. CONCLUSIONS: The success rates reported in the literature of more
      than 90% appear to be very high. This study demonstrates that high long-term
      success rates are very difficult to achieve even in rhinosurgical centres.
      Deviations from results of other studies can be explained by very short follow-up
      periods and a retrospective study design in almost all cases. An appropriate
      informed consent of the patient before surgery is important in order to achieve
      realistic expectations.

PMID- 25369160
TI  - [Physical characterization of decellularized cartilage matrix for reconstructive
      rhinosurgery].
AB  - BACKGROUND: The use of autologous auricular and rib cartilage for the
      reconstruction of nasal defects and deformities is associated with a number of
      disadvantages. The development of alternative materials is therefore the focus of
      intensive research. Recent studies demonstrated that decellularized cartilage is
      a promising material for cartilage tissue engineering. Hence, the aim of this
      study was to characterize the materials surface and cellular reactions to the
      decellularized cartilage matrix in long term-3D-culture. MATERIAL AND METHODS:
      Material geometry of decellularized cartilage was examined by microcomputed
      tomography as well as material characteristics by scanning and transmission
      electron microscopy. The expression of integrins on the surface of human
      chondrocytes was determined after seeding and migration into the scaffold.
      RESULTS: After decellularization an obvious enlargement of the matrix surface and
      an intensive interaction between the chondrocytes and the collagen matrix was
      observed. ITGA1 and ITGB1 were upregulated indicating chondrogenic
      differentiation. CONCLUSION: Therefore, decellularized porcine cartilage provides
      an optimal microstructure for human chondrocytes with respect to cell integration
      and matrix production. Thus, it offers promising characteristics for clinical
      application in reconstructive surgery.

PMID- 25369161
TI  - [Prevalence of depression and body dysmorphic disorder in patients before
      functional rhinosurgery].
AB  - OBJECTIVE: Psychiatric disorders are known to influence the result of many
      surgical procedures. Body dysmorphic disorder (BDD) is found in many patients
      undergoing plastic surgery. The prevalence before functional rhinosurgery has not
      been examined so far. The aim of this study was to determine the prevalence of
      depression and BDD before functional rhinosurgery. MATERIAL AND METHODS: 201
      patients were prospectively examined with a questionnaire before functional
      rhinosurgery. Beck-Depression-Index was used to rate depression, the PISA body
      dsymorphic symptom scale was used to evaluate the likelihood that a patient
      suffers from body dysmoprhic disorder. RESULTS: 186 patients returned a complete
      questionnaire. In 33.9% showed a mild or strong indication for a body dysmorphic
      disorder. Patients who were planned to undergo septorhinoplasty had a
      significantly higher scores in the PISA-scale compared to patients before
      septoplasty. 1.7% patients were depressive without a significant difference
      between the planned surgical procedure. CONCLUSION: Many patients before
      functional septorhinoplasty show signs of body dysmorphic disorder. Whether this
      influences the subjective clinical outcome needs to be evaluated in further
      studies.

PMID- 25369162
TI  - [Anterior skull base defects - algorithm for reconstruction].
AB  - BACKGROUND: After tumor surgery or traumatic defects the anterior skull base
      needs sufficient closure in order to prevent rhinoliquorrhea, ascending infection
      and brain tissue prolaps. Small defects are sufficiently closed by non-vital
      tissue, e. g. mucosa, muscle, fat, fascia, bone, allogenic, xenogenic or
      alloplastic material. Larger defects of the skull base often require more
      extensive surgery, including transfer of local or distal vascularized flaps. The
      current article presents a stepwise tutorial for reconstruction of the skull base
      and by a large case series focuses on the interdisciplinary therapy of complex
      (size, recurrence, after radiotherapy) skull base defects. MATERIAL AND METHOD:
      Complex defects with small diameter, which can occur after extended sinus
      surgery, were permanently closed by local mucosa flaps of the lower turbinate or
      of the septum (n=31). Larger defects, e. g. after combined transcranial and
      endonasal tumor surgery, were closed by a 'sandwich technique' containing a galea
      periost flap and a calvarian split transfer (n=10). Reconstruction of the dura
      with fascia lata and local transfer of the temporal muscle were efficient for
      frontobasal defects with a more lateral location (n=4). Transfer of a distal
      desepithelialised vascularized forearm flap represents the ultimate procedure for
      reconstruction of large skull base defects, which was performed in 4 of our
      patients. CONCLUSION: Successive escalation of the therapy and integra-tion of
      the entire repertoire of plastic-reconstructive surgery allows for durable
      closure of complex skull base defects. In every case, close cooperation between
      ENT- and neurosurgeons is necessary for planning and performance of a successful
      surgical procedure.

PMID- 25369163
TI  - [Functional and aesthetic outcome after surgery on cleft lip nasal deformities].
AB  - OBJECTIVE: Patients with cleft lip nasal deformities suffer not only from
      aesthetic stigmatization but also from functional problems. Many different
      techniques to operate on this deformity have been described. METHODS: 24 patients
      (16 male and 8 female, aged 20-56 years) have been enrolled in this study. A
      subjective value of the postoperative result of aesthetics and function was
      measured by a visual analogue scale ranging from - 5 (significant aggravation) to
      +5 (significant improvement) including 0 (no change). Additionally the primary
      nasal symptoms (PNS) of the SNOT-20 GAV were collected. RESULTS: 10 primary
      surgeries and 14 revisions were performed with 20 open and 4 endonasal
      approaches. In 11 cases a composite graft from the concha was used. 75% of the
      patients looked up to both features aesthetic and function favorably. The mean
      evaluation was +3.4 for aesthetics and +2.6 for function. 91% of the patients who
      received a composite graft looked up to the result favorably. The mean PNS were
      14. CONCLUSIONS: Altogether good results especially concerning the subjective
      aesthetics can be achieved by precise preoperative evaluation and the described
      operative algorithm. In our sample of patients better results could be
      accomplished by using composite grafts. Nevertheless it seems to be more
      difficult to improve the function of cleft lip nasal deformities than the
      aesthetics. More innovations and objective measurements are needed to come up to
      the still unsolved problems of the challenging surgery of cleft lip nasal
      deformities.

PMID- 25369164
TI  - [An unusual case of late metastases].

PMID- 25369165
TI  - [From the expert's office: expert assessment and compensation of noise induced
      tinnitus].

PMID- 25369166
TI  - [Hypernasal speech (rhinolalia aperta) as a possible consequence of
      septorhinoplastic in patients with palatal deficiencies].

PMID- 25369167
TI  - [Radiological imaging - magnetic resonance tomography - digital subtraction
      angiography].

PMID- 25369168
TI  - Cellular plasticity induced by anti-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor encephalitis antibodies.
AB  - OBJECTIVE: Autoimmune-mediated anti-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor (AMPAR) encephalitis is a severe but treatment
      responsive disorder with prominent short-term memory loss and seizures. The
      mechanisms by which patient antibodies affect synapses and neurons leading to
      symptoms are poorly understood. METHODS: The effects of patient antibodies on
      cultures of live rat hippocampal neurons were determined with immunostaining,
      Western blot, and electrophysiological analyses. RESULTS: We show that patient
      antibodies cause a selective decrease in the total surface amount and synaptic
      localization of GluA1- and GluA2-containing AMPARs, regardless of receptor
      subunit binding specificity, through increased internalization and degradation of
      surface AMPAR clusters. In contrast, patient antibodies do not alter the density
      of excitatory synapses, N-methyl-D-aspartate receptor (NMDAR) clusters, or cell
      viability. Commercially available AMPAR antibodies directed against extracellular
      epitopes do not result in a loss of surface and synaptic receptor clusters,
      suggesting specific effects of patient antibodies. Whole-cell patch clamp
      recordings of spontaneous miniature postsynaptic currents show that patient
      antibodies decrease AMPAR-mediated currents, but not NMDAR-mediated currents.
      Interestingly, several functional properties of neurons are also altered:
      inhibitory synaptic currents and vesicular gamma-aminobutyric acid transporter
      (vGAT) staining intensity decrease, whereas the intrinsic excitability of neurons
      and short-interval firing increase. INTERPRETATION: These results establish that
      antibodies from patients with anti-AMPAR encephalitis selectively eliminate
      surface and synaptic AMPARs, resulting in a homeostatic decrease in inhibitory
      synaptic transmission and increased intrinsic excitability, which may contribute
      to the memory deficits and epilepsy that are prominent in patients with this
      disorder.

PMID- 25369169
TI  - Hydride binding to the active site of [FeFe]-hydrogenase.
AB  - [FeFe]-hydrogenase from green algae (HydA1) is the most efficient hydrogen (H2)
      producing enzyme in nature and of prime interest for (bio)technology. Its active
      site is a unique six-iron center (H-cluster) composed of a cubane cluster,
      [4Fe4S]H, cysteine-linked to a diiron unit, [2Fe]H, which carries unusual carbon
      monoxide (CO) and cyanide ligands and a bridging azadithiolate group. We have
      probed the molecular and electronic configurations of the H-cluster in functional
      oxidized, reduced, and super-reduced or CO-inhibited HydA1 protein, in particular
      searching for intermediates with iron-hydride bonds. Site-selective X-ray
      absorption and emission spectroscopy were used to distinguish between low- and
      high-spin iron sites in the two subcomplexes of the H-cluster. The experimental
      methods and spectral simulations were calibrated using synthetic model complexes
      with ligand variations and bound hydride species. Distinct X-ray spectroscopic
      signatures of electronic excitation or decay transitions in [4Fe4S]H and [2Fe]H
      were obtained, which were quantitatively reproduced by density functional theory
      calculations, thereby leading to specific H-cluster model structures. We show
      that iron-hydride bonds are absent in the reduced state, whereas only in the
      super-reduced state, ligand rotation facilitates hydride binding presumably to
      the Fe-Fe bridging position at [2Fe]H. These results are in agreement with a
      catalytic cycle involving three main intermediates and at least two protonation
      and electron transfer steps prior to the H2 formation chemistry in [FeFe]
      hydrogenases. 

PMID- 25369171
TI  - Photoisomerization and proton transfer in the forward and reverse photoswitching
      of the fast-switching M159T mutant of the Dronpa fluorescent protein.
AB  - The fast-switching M159T mutant of the reversibly photoswitchable fluorescent
      protein Dronpa has an enhanced yield for the on-to-off reaction. The forward and
      reverse photoreactions proceed via cis-trans and trans-cis photoisomerization,
      yet protonation and deprotonation of the hydroxyphenyl oxygen of the chromophore
      is responsible for the majority of the resulting spectroscopic contrast.
      Ultrafast visible-pump, infrared-probe spectroscopy was used to detect the
      picosecond, nanosecond, as well as metastable millisecond intermediates.
      Additionally, static FTIR difference measurements of the Dronpa-M159T mutant
      correspond very closely to those of the wild type Dronpa, identifying the p
      hydroxybenzylidene-imidazolinone chromophore in the cis anion and trans neutral
      forms in the bright "on" and dark "off" states, respectively. Green excitation of
      the on state is followed by dominant radiative decay with characteristic time
      constants of 1.9 ps, 185 ps, and 1.1 ns, and additionally reveals spectral
      changes belonging to the species decaying with a 1.1 ns time constant, associated
      with both protein and chromophore modes. A 1 ms measurement of the on state
      identifies bleach features that correspond to those seen in the static off-minus
      on Fourier transform infrared (FTIR) difference spectrum, indicating that thermal
      protonation of the hydroxyphenyl oxygen proceeds within this time window. Blue
      excitation of the off state directly resolves the formation of the primary
      photoproduct with 0.6 and 14 ps time constants, which is stable on the nanosecond
      time scale. Assignment of the primary photoproduct to the cis neutral chromophore
      in the electronic ground state is supported by the frequency positions expected
      relative to those for the nonplanar distorted geometry for the off state. A 1 ms
      measurement of the off state corresponds closely with the on-minus-off FTIR
      difference spectrum, indicating thermal deprotonation and rearrangement of the
      Arg66 side chain to be complete. 

PMID- 25369170
TI  - Rapid antigen group A streptococcus test to diagnose pharyngitis: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Pharyngitis management guidelines include estimates of the test
      characteristics of rapid antigen streptococcus tests (RAST) using a non
      systematic approach. OBJECTIVE: To examine the sensitivity and specificity, and
      sources of variability, of RAST for diagnosing group A streptococcal (GAS)
      pharyngitis. DATA SOURCES: MEDLINE, Cochrane Reviews, Centre for Reviews and
      Dissemination, Scopus, SciELO, CINAHL, guidelines, 2000-2012. STUDY SELECTION:
      Culture as reference standard, all languages. DATA EXTRACTION AND SYNTHESIS:
      Study characteristics, quality. MAIN OUTCOME(S) AND MEASURE(S): Sensitivity,
      specificity. RESULTS: We included 59 studies encompassing 55,766 patients. Forty
      three studies (18,464 patients) fulfilled the higher quality definition (at least
      50 patients, prospective data collection, and no significant biases) and 16
      (35,634 patients) did not. For the higher quality immunochromatographic methods
      in children (10,325 patients), heterogeneity was high for sensitivity
      (inconsistency [I(2)] 88%) and specificity (I(2) 86%). For enzyme immunoassay in
      children (342 patients), the pooled sensitivity was 86% (95% CI, 79-92%) and the
      pooled specificity was 92% (95% CI, 88-95%). For the higher quality
      immunochromatographic methods in the adult population (1,216 patients), the
      pooled sensitivity was 91% (95% CI, 87 to 94%) and the pooled specificity was 93%
      (95% CI, 92 to 95%); however, heterogeneity was modest for sensitivity (I(2) 61%)
      and specificity (I(2) 72%). For enzyme immunoassay in the adult population (333
      patients), the pooled sensitivity was 86% (95% CI, 81-91%) and the pooled
      specificity was 97% (95% CI, 96 to 99%); however, heterogeneity was high for
      sensitivity and specificity (both, I(2) 88%). CONCLUSIONS: RAST
      immunochromatographic methods appear to be very sensitive and highly specific to
      diagnose group A streptococcal pharyngitis among adults but not in children. We
      could not identify sources of variability among higher quality studies. The
      present systematic review provides the best evidence for the wide range of
      sensitivity included in current guidelines.

PMID- 25369173
TI  - Synthesis, characterization, and evaluation of 10-undecenoic acid-based epithio
      derivatives as multifunctional additives.
AB  - Novel epithio compounds from alkyl epoxy undecanoates (n-alkyl, C1, C4, and C6;
      isoalkyl, C3, C4, and C8) were synthesized using an ammonium thiocyanate in ionic
      liquid 1-methylimidazolium tetrafluoroborate/H2O (2:1) solvent system in 85-90%
      yields by gas chromatographic (GC) analysis. The synthesized products were
      characterized by (1)H and (13)C nuclear magnetic resonance spectroscopy, Fourier
      transform infrared spectroscopy (FTIR), gas chromatography, and GC mass spectral
      (GC-MS) analyses and evaluated for their antioxidant, extreme pressure (EP), and
      antiwear (AW) properties in three different base oils, namely, epoxy jatropha
      fatty acid n-butyl esters (EJB), di-2-ethylhexyl sebacate (DOS), and mineral oil
      (S-105). Among the synthesized products, n-butyl epithio undecanoate exhibited
      superior antioxidant property (229.2  degrees C) compared to butylated
      hydroxytoluene (BHT, 193.8  degrees C) in base oil DOS and comparable performance
      in EJB and S-105 base oils. All of the epithio derivatives exhibited
      significantly enhanced weld point for the base oils EJB and DOS at 2 wt % level
      and displayed moderate enhancement in S-105 base oil. Methyl epithio undecanoate
      at 0.6% concentration exhibited considerable improvement in the wear scar of DOS
      base oil. The synthesized epithio derivatives have potential as multifunctional
      additives in lubricant formulations. 

PMID- 25369172
TI  - Immune-correlates analysis of an HIV-1 vaccine efficacy trial reveals an
      association of nonspecific interferon-gamma secretion with increased HIV-1
      infection risk: a cohort-based modeling study.
AB  - BACKGROUND: Elevated risk of HIV-1 infection among recipients of an adenovirus
      serotype 5 (Ad5)-vectored HIV-1 vaccine was previously reported in the Step HIV-1
      vaccine efficacy trial. We assessed pre-infection cellular immune responses
      measured at 4 weeks after the second vaccination to determine their roles in HIV
      1 infection susceptibility among Step study male participants. METHODS: We
      examined ex vivo interferon-gamma (IFN-gamma) secretion from peripheral blood
      mononuclear cells (PBMC) using an ELISpot assay in 112 HIV-infected and 962
      uninfected participants. In addition, we performed flow cytometric assays to
      examine T-cell activation, and ex vivo IFN-gamma and interleukin-2 secretion from
      CD4(+) and CD8(+) T cells. We accounted for the sub-sampling design in Cox
      proportional hazards models to estimate hazard ratios (HRs) of HIV-1 infection
      per 1-log(e) increase of the immune responses. FINDINGS: We found that HIV
      specific immune responses were not associated with risk of HIV-1 infection.
      However, each 1-log(e) increase of mock responses measured by the ELISpot assay
      (i.e., IFN-gamma secretion in the absence of antigen-specific stimulation) was
      associated with a 62% increase of HIV-1 infection risk among vaccine recipients
      (HR = 1.62, 95% CI: (1.28, 2.04), p<0.001). This association remains after
      accounting for CD4(+) or CD8(+) T-cell activation. We observed a moderate
      correlation between ELISpot mock responses and CD4(+) T-cells secreting IFN-gamma
      (rho = 0.33, p = 0.007). In addition, the effect of the Step vaccine on infection
      risk appeared to vary with ELISpot mock response levels, especially among
      participants who had pre-existing anti-Ad5 antibodies (interaction p = 0.04).
      CONCLUSIONS: The proportion of cells, likely CD4(+) T-cells, producing IFN-gamma
      without stimulation by exogenous antigen appears to carry information beyond T
      cell activation and baseline characteristics that predict risk of HIV-1
      infection. These results motivate additional investigation to understand the
      potential link between IFN-gamma secretion and underlying causes of elevated HIV
      1 infection risk among vaccine recipients in the Step study.

PMID- 25369174
TI  - Effects of Korean red ginseng extract on behavior in children with symptoms of
      inattention and hyperactivity/impulsivity: a double-blind randomized placebo
      controlled trial.
AB  - Abstract Objective: There is evidence that Korean red ginseng (KRG) can reduce
      the production of the adrenal corticosteroids, cortisol, and
      dehydroepiandrosterone (DHEA), and thus may be a viable treatment for attention
      deficit/hyperactivity disorder (ADHD). The present randomized double-blind
      placebo-controlled clinical trial tested the effect of KRG on children with ADHD
      symptoms. METHODS: Subjects 6-15 years, who satisfied the inclusion criteria and
      had ADHD symptoms, were randomized into a KRG group (n=33) or a control group
      (n=37). The KRG group received one pouch of KRG (1g KRG extract/pouch) twice a
      day, and the control group received one pouch of placebo twice a day. At the 8
      week point, the primary outcomes were the Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV) criteria for inattention and hyperactivity scale
      scores, which were measured at baseline and 8 weeks after starting treatment.
      Secondary outcomes were quantitative electroencephalography theta/beta ratio
      (QEEG TBR) (measured at baseline and week 8) and salivary cortisol and DHEA
      levels (measured at baseline and at 4 and 8 weeks). RESULTS: The baseline
      characteristics of the KRG and control groups were not statistically different.
      The mean ages of the KRG and control groups were 10.94+/-2.26 and 10.86+/-2.41,
      respectively. The KRG group had significantly decreased inattention/hyperactivity
      scores compared with the control group at week 8 (least squared means of the
      differences in inattention adjusted for baseline scores: -2.25 vs. -1.24,
      p=0.048; hyperactivity: -1.53 vs. -0.61, p=0.047). The KRG group had
      significantly decreased QEEG TBR compared with the control group (least squared
      means of the differences: -0.94 vs. -0.14, p=0.001). However, neither the KRG
      group nor the control group exhibited significant differences in salivary
      cortisol or DHEA levels at week 8 compared with the baseline levels. No serious
      adverse events were reported in either group. CONCLUSIONS: These results suggest
      that KRG extract may be an effective and safe alternative treatment for children
      with inattention and hyperactivity/impulsivity symptoms. Further studies to
      investigate the efficacy and safety of KRG are warranted.

PMID- 25369175
TI  - Paraneoplastic pemphigus associated with inflammatory myofibroblastic tumour of
      the mediastinum: A favourable response to treatment and review of the literature.
AB  - Paraneoplastic pemphigus (PNP) is an autoimmune blistering disorder that occurs
      in association with an underlying neoplasm. Inflammatory myofibroblastic tumour
      (IMT) is a rare low-grade sarcoma of fibroblasts and myofibroblasts associated
      with inflammatory cells, most commonly occurring in the lung. In this study, a
      case of PNP associated with IMT of the mediastinum is reported. The patient had a
      favourable outcome following surgical resection and treatment with a systemic
      steroid, azathioprine, and i.v. immunoglobulin. The occurrence of PNP with
      sarcomas, specifically IMT, is noteworthy although it is not well studied in the
      existing literature. 

PMID- 25369176
TI  - Enhanced thermic effect of food, postprandial NEFA suppression and raised
      adiponectin in obese women who eat slowly.
AB  - OBJECTIVE: Meal duration may influence cardiometabolic health. The aim of this
      study was to explore postprandial effects of meal duration on human metabolism
      and appetite. DESIGN: Postprandial comparisons following a standard meal eaten
      slowly over 40 min ('D40') and the same meal eaten quickly over 10 min ('D10') on
      a different day. Each participant therefore acted as their own control, thereby
      limiting confounding factors. PATIENTS: Obese premenopausal Caucasian women (n =
      10) with confirmed normoglycaemia were recruited from an obesity clinic at UHCW,
      Coventry UK. Subjects underwent whole-body calorimetry (8-h) on two separate
      days. MEASUREMENTS: Following standard lunch (D40 vs D10), 4-h postprandial
      analysis included thermic effect of food (TEF) and bloods taken at predefined
      times (including baseline fasting). Analytes included lipid profile, adiponectin,
      insulin, glucose, ghrelin, leptin, endotoxin, gut and pancreatic hormones.
      Appetite was measured using visual-analogue scales and ad libitum food intake at
      subsequent meal. Paired sample t-tests [including area under the curve (AUC)]
      were used to compare D40 and D10 trials. RESULTS: Postprandial TEF (over 240-min)
      was significantly greater for D40 than D10 [mean (SEM): 80.9 kcal (3.8) vs 29.9
      kcal (3.4); 10.6% vs 3.9%, respectively, P = 0.006; AUC 71.7 kcal.h vs 22.4
      kcal.h, respectively, P = 0.02]. Postprandial plasma NEFA was significantly
      lower, and adiponectin levels were significantly higher for D40 than D10 [AUC
      (SEM): NEFA 627 MUmol.h/l (56) vs 769 MUmol.h/l (60), respectively, P = 0.02;
      adiponectin 33.4 MUg.h/ml (3.9) vs 27.3 MUg.h/ml (3.8), respectively, P = 0.04].
      Other postprandial analytes and appetite measures were equivalent. CONCLUSIONS:
      In obese women, eating slowly associates with enhanced TEF, elevated serum
      adiponectin and suppressed NEFA.

PMID- 25369177
TI  - Metabolic, immune, and gut microbial signals mount a systems response to
      Leishmania major infection.
AB  - Parasitic infections such as leishmaniasis induce a cascade of host physiological
      responses, including metabolic and immunological changes. Infection with
      Leishmania major parasites causes cutaneous leishmaniasis in humans, a neglected
      tropical disease that is difficult to manage. To understand the determinants of
      pathology, we studied L. major infection in two mouse models: the self-healing
      C57BL/6 strain and the nonhealing BALB/c strain. Metabolic profiling of urine,
      plasma, and feces via proton NMR spectroscopy was performed to discover parasite
      specific imprints on global host metabolism. Plasma cytokine status and fecal
      microbiome were also characterized as additional metrics of the host response to
      infection. Results demonstrated differences in glucose and lipid metabolism,
      distinctive immunological phenotypes, and shifts in microbial composition between
      the two models. We present a novel approach to integrate such metrics using
      correlation network analyses, whereby self-healing mice demonstrated an
      orchestrated interaction between the biological measures shortly after infection.
      In contrast, the response observed in nonhealing mice was delayed and fragmented.
      Our study suggests that trans-system communication across host metabolism, the
      innate immune system, and gut microbiome is key for a successful host response to
      L. major and provides a new concept, potentially translatable to other diseases. 

PMID- 25369178
TI  - Size distribution of airborne particle-bound polybrominated diphenyl ethers and
      its implications for dry and wet deposition.
AB  - Size distribution of particles in part dictates the environmental behavior of
      particle-bound organic pollutants in the atmosphere. The present study was
      conducted to examine the potential mechanisms responsible for the distribution of
      organic pollutants in size fractionated particles and their environmental
      implications, using an e-waste recycling zone in South China as a case study.
      Size-fractionated atmospheric particles were collected at the heights of 1.5, 5,
      and 20 m near two residential apartments and analyzed for polybrominated diphenyl
      ethers (PBDEs). The concentrations of particle-bound SigmaPBDE (sum of 18 PBDE
      congeners) were significantly greater at 5 and 20 m than those at 1.5 m. The size
      fractionated distributions of airborne SigmaPBDE displayed trimodal peaks in 0.10
      0.18, 1.8-3.2, and 10-18 MUm at 1.5 m but only an unimodal peak in 1.0-1.8 MUm at
      20 m height. Emission sources, resuspension of dust and soil, and volatility of
      PBDEs were important factors influencing the size distribution of particle-bound
      PBDEs. The dry deposition fluxes of particle-bound PBDE estimated from the
      measured data in the present study were approximately twice the estimated wet
      deposition fluxes, with a total deposition flux of 3000 ng m(-2) d(-1). The
      relative contributions of particles to dry and wet deposition fluxes were also
      size-dependent, e.g., coarse (aerodynamic diameters (Dp) > 1.8 MUm) and fine (Dp
      < 1.8 MUm) particles dominated the dry and wet deposition fluxes of PBDEs,
      respectively.

PMID- 25369179
TI  - Exposure rate of smooth surface tunnel porous polyethylene implants after
      enucleation.
AB  - PURPOSE: To determine the exposure rate after enucleation using the smooth
      surface tunnel (SST) and SST-EZ porous polyethylene (PP) orbital implants
      (Stryker Kalamazoo, MI, U.S.A.). METHODS: The authors performed an institutional
      review board-approved retrospective review of 150 consecutively placed SST and
      SST-EZ PP implants after enucleation. Patient records were reviewed for
      comorbidities, surgical details, follow-up length, and presence of implant
      exposure. All prior published studies on porous orbital implant insertion were
      reviewed, and the exposure rate for patients undergoing enucleation with primary
      implant insertion was studied for comparison. RESULTS: Of the 150 implants, 30
      were excluded due to follow up of less than 8 weeks. Of the remaining 120
      implants, 4 (3.3%) became exposed during the follow-up period (mean, 2.1 years),
      2 of which were in children who underwent chemotherapy for retinoblastoma. The
      authors calculated a 7.1% exposure rate for all porous implant materials placed
      primarily after enucleation from 58 previously published studies. CONCLUSIONS:
      The SST and SST-EZ PP implants are well tolerated when placed at the time of
      enucleation. The theoretical advantage of a smooth anterior surface may indeed
      lead to a lower rate of exposure compared with standard unwrapped porous
      materials as demonstrated by the relatively low exposure rate using this implant.

PMID- 25369180
TI  - Aromaticity, closed-shell effects, and metallization of hydrogen.
AB  - CONSPECTUS: Recent theoretical and experimental studies reveal that compressed
      molecular hydrogen at 200-350 GPa transforms to layered structures consisting of
      distorted graphene sheets. The discovery of chemical bonding motifs in these
      phases that are far from close-packed contrasts with the long-held view that
      hydrogen should form simple, symmetric, ambient alkali-metal-like structures at
      these pressures. Chemical bonding considerations indicate that the realization of
      such unexpected structures can be explained by consideration of simple low
      dimensional model systems based on H6 rings and graphene-like monolayers. Both
      molecular quantum chemistry and solid-state physics approaches show that these
      model systems exhibit a special stability, associated with the completely filled
      set of bonding orbitals or valence bands. This closed-shell effect persists in
      the experimentally observed layered structures where it prevents the energy gap
      from closing, thus delaying the pressure-induced metallization. Metallization
      occurs upon further compression by destroying the closed shell electronic
      structure, which is mainly determined by the 1s electrons via lowering of the
      bonding bands stemming from the unoccupied atomic 2s and 2p orbitals. Because
      enhanced diamagnetic susceptibility is a fingerprint of aromaticity, magnetic
      measurements provide a potentially important tool for further characterization of
      compressed hydrogen. The results indicate that the properties of dense hydrogen
      are controlled by chemical bonding forces over a much broader range of conditions
      than previously considered.

PMID- 25369181
TI  - Hepatobiliary malignancies in Wilson disease.
AB  - BACKGROUNDS & AIMS: Reports of hepatobiliary malignancies in Wilson disease are
      sparse. The aim of this study was to evaluate hepatobiliary malignancies in
      Wilson disease patients concerning the clinical course of tumour disease and
      pathological analysis of tumour tissue. METHODS: Multicenter cohort study of
      patients with confirmed diagnosis of Wilson disease treated at the Second
      Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland,
      the university hospitals Heidelberg, Duesseldorf and Dresden, Germany, and the
      Department of Hepatology, University Leuven, Belgium. Occurrence, treatment and
      outcome of hepatobiliary tumours were analysed retrospectively. RESULTS: Of a
      total of 1186 patients, fourteen developed hepatobiliary malignancies. Eight were
      hepatocellular carcinomas (HCC) and six were intrahepatic cholangiocellular
      carcinomas (ICC). The prevalence of hepatobiliary malignancies in the cohort was
      1.2% and the incidence was 0.28 per 1000 person years. Pathological analysis of
      tumour material showed no abnormal copper concentration. CONCLUSIONS: The rate of
      hepatobiliary malignancies in Wilson disease is very low, even in cirrhotic
      patients. As a result of the relevant number of ICC in addition to HCC
      histological analysis through surgical resection or biopsy should be mandatory
      when a suspect liver lesion is detected. The influence of copper depletion from
      Wilson disease-specific medical treatment on tumour activity remains to be
      elucidated.

PMID- 25369182
TI  - Advances in melanocyte and melanoma biology.

PMID- 25369184
TI  - Leading by example.

PMID- 25369185
TI  - Implementing change: involving employees to improve outcomes.
AB  - Increasingly, pharmacy workplaces are larger organizations that rely on policy
      and clinical guidelines to direct professional practice. Often, cost-cutting,
      profit-making, service-improving, and process-streamlining ideas are needed but
      difficult to identify or implement. By involving employees more closely in the
      change process using participative management (PM), managers reap tremendous
      reward. PM focuses on employee collaboration to develop and implement consistent,
      effective policies and procedures. This process recognizes employees' creative,
      emotional and intellectual needs and often improves the organization's public
      face as well. In addition, consumers perceive this approach to be socially
      responsible management. Managers can implement PM in a number of ways, applying
      it to problems or processes. PM has some pitfalls, but overall, if the workplace
      culture adapts to accommodate its principles, PM usually provides numerous
      benefits for organizations, their employees, and their customers. 

PMID- 25369183
TI  - Vesicles bearing Toxoplasma apicoplast membrane proteins persist following loss
      of the relict plastid or Golgi body disruption.
AB  - Toxoplasma gondii and malaria parasites contain a unique and essential relict
      plastid called the apicoplast. Most apicoplast proteins are encoded in the
      nucleus and are transported to the organelle via the endoplasmic reticulum (ER).
      Three trafficking routes have been proposed for apicoplast membrane proteins: (i)
      vesicular trafficking from the ER to the Golgi and then to the apicoplast, (ii)
      contiguity between the ER membrane and the apicoplast allowing direct flow of
      proteins, and (iii) vesicular transport directly from the ER to the apicoplast.
      Previously, we identified a set of membrane proteins of the T. gondii apicoplast
      which were also detected in large vesicles near the organelle. Data presented
      here show that the large vesicles bearing apicoplast membrane proteins are not
      the major carriers of luminal proteins. The vesicles continue to appear in
      parasites which have lost their plastid due to mis-segregation, indicating that
      the vesicles are not derived from the apicoplast. To test for a role of the Golgi
      body in vesicle formation, parasites were treated with brefeldin A or transiently
      transfected with a dominant-negative mutant of Sar1, a GTPase required for ER to
      Golgi trafficking. The immunofluorescence patterns showed little change. These
      findings were confirmed using stable transfectants, which expressed the toxic
      dominant-negative sar1 following Cre-loxP mediated promoter juxtaposition. Our
      data support the hypothesis that the large vesicles do not mediate the
      trafficking of luminal proteins to the apicoplast. The results further show that
      the large vesicles bearing apicoplast membrane proteins continue to be observed
      in the absence of Golgi and plastid function. These data raise the possibility
      that the apicoplast proteome is generated by two novel ER to plastid trafficking
      pathways, plus the small set of proteins encoded by the apicoplast genome. 

PMID- 25369186
TI  - Sharon F. Clackum: tackling down-to-earth Priorities.
AB  - Sharon F. Clackum, incoming 2014-2015 ASCP president, will be tackling the down
      to-earth priorities facing consultant pharmacists every day: improving medication
      therapy for older adults, increasing public awareness of the services they
      provide, and achieving recognition by Medicare as health professionals who need
      to be paid. 

PMID- 25369187
TI  - Use of an interactive trivia game to increase knowledge and awareness of
      appropriate antibiotic use in community-dwelling older adults: a pilot survey.
AB  - OBJECTIVE: To assess change in knowledge and awareness of upper respiratory-tract
      infections (URTIs), and appropriate antibiotic use in community-dwelling older
      adults. DESIGN: Single group, pre- and post-test study. SETTING: Two independent
      senior living communities in Baltimore City and Baltimore County, Maryland.
      PARTICIPANTS: Older adults eligible to receive housing or other social services
      as defined by the study sites. INTERVENTION: Use of an interactive trivia game to
      educate older adults about URTIs. A 15-item pre- and postsurvey was administered
      to assess change in knowledge. OUTCOME MEASURES: Average change in pre- and
      postsurvey scores. RESULTS: Thirty-two seniors participated in the game
      intervention, with 18 completing both surveys. There was no significant
      difference in the total mean pre- versus postsurvey scores. Average scores of pre
      and postsurveys were 9.28 and 9.17, respectively, out of 15 points (95%
      confidence interval 0.65 +/- 1.414; P = 0.76). Upon review of individual survey
      questions, two specific areas showed a significant improvement on postsurvey
      scores compared with baseline. Participants showed significant improvement,
      however, in knowledge regarding symptoms that may require the use of an
      antibiotic (P = 0.02) and symptomatic management of URTI symptoms (P = 0.045).
      CONCLUSIONS: Based on survey results, we learned more about older adults'
      knowledge regarding URTIs, antibiotic use, and strategies to provide education to
      community-dwelling geriatric adults. The game was effective in teaching older
      adults about symptom management and symptoms that may require an antibiotic.

PMID- 25369188
TI  - Bleeding incidence and real-life prescribing practices with dabigatran use in an
      acute care setting.
AB  - OBJECTIVES: Since dabigatran's emergence in the United States market for use in
      preventing stroke and systemic embolism in nonvalvular atrial fibrillation, the
      Food and Drug Administration has issued two safety alerts for serious bleeding
      events. The postmarketing findings, along with anecdotal clinician concerns,
      prompted this drug utilization evaluation for dabigatran. SETTING: We included
      all adult patients administered dabigatran from January 1, 2011, to December 31,
      2011, while admitted to a large university-affiliated medical center. PRACTICE
      DESCRIPTION: Dabigatran is available on formulary with a dosing and monitoring
      policy developed by a multidisciplinary subcommittee of the formulary and
      therapeutics committee. PRACTICE INNOVATION: This is an institutional review
      board-approved retrospective chart review of 172 patients administered dabigatran
      during hospitalization. MAIN OUTCOME MEASUREMENT: Incidence of gastrointestinal
      bleeds and minor bleeds with the use of dabigatran. RESULTS: The incidence of
      gastrointestinal bleeds in our study was 2.3% and minor bleeds was 2.3%. Doses
      outside of the manufacturer's recommendations were not associated with overt
      bleeds while in the hospital. CONCLUSION: Our results demonstrate that the
      incidence of bleeds experienced with dabigatran was relatively low despite the
      reports received by FDA.

PMID- 25369189
TI  - Role of pharmacists in the treatment of excessive daytime sleepiness.
AB  - The focus of this case is a 78-year-old female who is being referred to an
      assisted living community following several episodes of excessive daytime
      sleepiness (EDS). EDS in the geriatric patient is widespread and is often
      underdiagnosed and inadequately treated. It can affect an older patient?s quality
      of life, as well as increasing physical, psychological, cognitive, and mortality
      risks. There are many different etiologies for EDS including coexisting medical
      conditions, circadian misalignment, medications affecting the sleep/wake cycle,
      and psychiatric or psychosocial circumstances. This case illustrates how the
      pharmacist can help patients with EDS by recognizing symptoms; performing a
      targeted medical history, sleep history, and medication review; and offering
      screening with validated tools to refer patients to sleep specialists. There are
      both pharmacological and nonpharmacological treatment options. The consultant
      pharmacist is a vital member of the interprofessional health care team and can
      play a major role in the education, monitoring, and management of EDS. 

PMID- 25369190
TI  - Potential problems and solutions with inhaler use in elderly COPD patients.
AB  - With the number of elderly people increasing each year, the potential problems of
      treating chronic obstructive pulmonary disease (COPD) in elderly patients is
      likely to become more prevalent. Naturally occurring changes during aging may
      lead to a change in treatment needs. Mental and dexterity decline can lead to
      increased difficulty operating the inhalers that are a staple of COPD treatment.
      Decreased respiratory strength can make it difficult for patients to achieve an
      adequate peak inspiratory force, which may prevent maximum benefit from inhaler
      use. Pharmacists have the unique opportunity of interacting with patients at the
      point of care and can make a significant impact by ensuring that these barriers
      are not affecting their patients. 

PMID- 25369192
TI  - DEA issues final rule on disposal of controlled substances.

PMID- 25369191
TI  - Credentialing and privileging of pharmacists: a resource paper from the Council
      on Credentialing in Pharmacy.

PMID- 25369193
TI  - Sexuality and affection among elderly German men and women in long-term
      relationships: results of a prospective population-based study.
AB  - Satisfaction with sexual activity i.e. sexual satisfaction and the importance of
      sexuality and affection were analysed using data from the German
      "Interdisciplinary Longitudinal Study of Adult Development" (ILSE). At three
      measurement points, 1993-1995, 1997-1998, and 2004-2006 i.e. subjects' ages of
      63, 67, and 74 years, participants' reports about their affection and sexual
      activity were collected. The sample of completed records used for this study
      consisted of 194 urban non-institutionalised participants, 68% male, all living
      with partners. Median levels of sexual satisfaction were reported, fluctuating
      between the measurement points of ages 63 to 74. Between baseline, first and
      second follow-up no differences were found in levels of sexual satisfaction,
      though at measurement points age 63 and 67 women were more satisfied than men.
      When measured at age 74, affection was given a higher priority than sexual
      activity. Although men and women reported similar priorities, sexual activity and
      affection were more important for men than for women. Satisfaction within the
      relationship can be predicted by the importance of affection, but not by that of
      sexual activity. Our results confirm the thesis of the 'second language of
      sexuality': for humans in their later years affection seems to be more important
      than for younger individuals. 

PMID- 25369194
TI  - Proton pump inhibitor intake neither predisposes to spontaneous bacterial
      peritonitis or other infections nor increases mortality in patients with
      cirrhosis and ascites.
AB  - BACKGROUND AND AIM: The aim of this study was to assess the impact of proton pump
      inhibitor (PPI) intake on the development of spontaneous bacterial peritonitis
      (SBP) or other infections, as well as on mortality, in a thoroughly documented
      cohort of patients with cirrhosis and ascites. PATIENTS AND METHODS: We performed
      a retrospective analysis of follow-up data from 607 consecutive patients with
      cirrhosis undergoing their first paracentesis at a tertiary center. A binary
      logistic regression model investigating the association between PPI intake and
      SBP at the first paracentesis was calculated. Competing risk analyses and Cox
      models were used to investigate the effect of PPIs on the cumulative incidence of
      SBP or other infections and transplant-free survival, respectively. Adjustments
      were made for age, hepatocellular carcinoma, history of variceal bleeding,
      varices and model of end-stage liver disease score. RESULTS: Eighty-six percent
      of patients were receiving PPIs. After adjusting for potential confounding
      factors, PPI intake was neither associated with increased SBP prevalence at the
      first paracentesis (odds ratio (OR):1.11,95% confidence interval (95%CI):0.6
      2.06; P = 0.731) nor cumulative incidence of SBP (subdistribution hazard ratio
      (SHR): 1.38; 95%CI:0.63-3.01; P = 0.42) and SBP or other infections (SHR:1.71;
      95%CI:0.85-3.44; P = 0.13) during follow-up. Moreover, PPI intake had no impact
      on transplant-free survival in both the overall cohort (hazard ratio
      (HR):0.973,95%CI:0.719-1.317; P = 0.859) as well as in the subgroups of patients
      without SBP (HR:1.01,95%CI:0.72-1.42; P = 0.971) and without SBP or other
      infections at the first paracentesis (HR:0.944,95%CI:0.668-1.334; P = 0.742).
      CONCLUSIONS: The proportion of cirrhotic patients with PPI intake was higher than
      in previous reports, suggesting that PPI indications were interpreted liberally.
      In our cohort with a particularly high prevalence of PPI intake, we observed no
      association between PPIs and SBP or other infections, as well as mortality. Thus,
      the severity of liver disease and other factors, rather than PPI treatment per se
      may predispose for infectious complications.

PMID- 25369195
TI  - Systematic CpT (ApG) depletion and CpG excess are unique genomic signatures of
      large DNA viruses infecting invertebrates.
AB  - Differences in the relative abundance of dinucleotides, if any may provide
      important clues on host-driven evolution of viruses. We studied dinucleotide
      frequencies of large DNA viruses infecting vertebrates (n = 105; viruses
      infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles =
      1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting
      crustaceans = 4). We have identified systematic depletion of CpT(ApG)
      dinucleotides and over-representation of CpG dinucleotides as the unique genomic
      signature of large DNA viruses infecting invertebrates. Detailed investigation of
      this unique genomic signature suggests the existence of invertebrate host-induced
      pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of
      CpT dinucleotides among large DNA viruses infecting invertebrates is at least in
      part, explained by non-canonical DNA methylation by the infected host. Our
      findings highlight the role of invertebrate host-related factors in shaping virus
      evolution and they also provide the necessary framework for future studies on
      evolution, epigenetics and molecular biology of viruses infecting this group of
      hosts.

PMID- 25369196
TI  - Molecular evolution and expansion analysis of the NAC transcription factor in Zea
      mays.
AB  - NAC (NAM, ATAF1, 2 and CUC2) family is a plant-specific transcription factor and
      it controls various plant developmental processes. In the current study, 124 NAC
      members were identified in Zea mays and were phylogenetically clustered into 13
      distinct subfamilies. The whole genome duplication (WGD), especially an
      additional WGD event, may lead to expanding ZmNAC members. Different subfamily
      has different expansion rate, and NAC subfamily preference was found during the
      expansion in maize. Moreover, the duplication events might occur after the
      divergence of the lineages of Z. mays and S. italica, and segmental duplication
      seemed to be the dominant pattern for the gene duplication in maize. Furthermore,
      the expansion of ZmNAC members may be also related to gain and loss of introns.
      Besides, the restriction of functional divergence was discovered after most of
      the gene duplication events. These results could provide novel insights into
      molecular evolution and expansion analysis of NAC family in maize, and advance
      the NAC researches in other plants, especially polyploid plants. 

PMID- 25369197
TI  - Mortality predictors in renal transplant recipients with severe sepsis and septic
      shock.
AB  - INTRODUCTION: The growing number of renal transplant recipients in a sustained
      immunosuppressive state is a factor that can contribute to increased incidence of
      sepsis. However, relatively little is known about sepsis in this population. The
      aim of this single-center study was to evaluate the factors associated with
      hospital mortality in renal transplant patients admitted to the intensive care
      unit (ICU) with severe sepsis and septic shock. METHODS: Patient demographics and
      transplant-related and ICU stay data were retrospectively collected. Multiple
      logistic regression was conducted to identify the independent risk factors
      associated with hospital mortality. RESULTS: A total of 190 patients were
      enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient
      age was 51 +/- 13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16
      23). The majority of patients developed sepsis late after the renal
      transplantation (2.1 [0.6-2.3] years). The lung was the most common infection
      site (59.5%). Upon ICU admission, 16.4% of the patients had <= 1 systemic
      inflammatory response syndrome criteria. Among the patients, 61.5% presented with
      >= 2 organ failures at admission, and 27.9% experienced septic shock within the
      first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%.
      In the multivariate analysis, the independent determinants of hospital mortality
      were male gender (OR = 5.9; 95% CI, 1.7-19.6; p = 0.004), delta SOFA 24 h (OR =
      1.7; 95% CI, 1.2-2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8
      102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0-22.6; p =
      0.002), admission from the ward (OR = 3.4; 95% CI, 1.2-9.7; p = 0.02) and acute
      kidney injury stage 3 (OR = 5.7; 95% CI,1.9-16.6; p = 0.002). CONCLUSIONS:
      Hospital mortality in renal transplant patients with severe sepsis and septic
      shock was associated with male gender, admission from the wards, worse SOFA
      scores on the first day and the presence of hematologic dysfunction, mechanical
      ventilation or advanced graft dysfunction.

PMID- 25369199
TI  - Vigna angularis water extracts protect against ultraviolet b-exposed skin aging
      in vitro and in vivo.
AB  - Exposure to ultraviolet (UV) radiation induces various pathological changes, such
      as thickened skin and wrinkle formation. In particular, UVB irradiation increases
      matrix metalloproteinase (MMP)-1 production and collagen degradation, leading to
      premature aging, termed photoaging. The azuki bean (Vigna angularis; VA) has been
      widely used as a food product as well as a traditional medicine. However, its
      activity needs additional study to confirm its functional application in foods
      and cosmetics for protecting skin. In this study, hot-water extract from VA (VAE)
      and its active component, rutin, were investigated to determine their
      antiphotoaging effects. VAE was found to have antioxidant activity. In UVB
      exposed normal human dermal fibroblasts cells with VAE and rutin treatments, MMP
      1 production was significantly suppressed (90% and 47%, respectively). The
      effects of both topical and oral administration of VAE were tested in UVB
      irradiated hairless mice. VAE suppressed wrinkle formation and skin thickness by
      promoting elastin, procollagen type I, and TGF-beta1 expression (118%, 156%, and
      136%, respectively) and by diminishing MMP-1 production. These results suggest
      that VAE may be effective for preventing skin photoaging accelerated by UVB
      radiation.

PMID- 25369198
TI  - CARD14 expression in dermal endothelial cells in psoriasis.
AB  - Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have
      recently been described in psoriasis patients, and explain the psoriasis
      susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates
      NF-kappaB activation, and psoriasis-associated CARD14 mutations lead to enhanced
      NF-kappaB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but
      also in unidentified dermal cells. In this manuscript, the identity of the dermal
      cell types expressing CARD14, as well the potential functional consequence of
      overactive CARD14 in these dermal cell types, was determined. Using two-color
      immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic
      cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31(+)
      endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells,
      such as aortic endothelial cells, which may indicate a role of CARD14(+)ECs in
      the systemic inflammation and cardiovascular comorbidities associated with
      psoriasis. Additionally, phosphorylated NF-kappaB was found in psoriatic
      CARD14(+) CD31(+) ECs, demonstrating this pathway is active in dermal ECs in
      psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations
      resulted in increased expression of several chemokines, including CXCL10, IL-8,
      and CCL2. These results provide preliminary evidence that CARD14 expression in
      ECs may contribute to psoriasis through increased expression of chemokines and
      facilitating recruitment of immune cells into skin.

PMID- 25369200
TI  - Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum
      hemorrhage in Uganda: a double-blind randomized non-inferiority trial.
AB  - BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal death in
      sub-Saharan Africa. Although the World Health Organization recommends use of
      oxytocin for prevention of PPH, misoprostol use is increasingly common owing to
      advantages in shelf life and potential for sublingual administration. There is a
      lack of data about the comparative efficacy of oxytocin and sublingual
      misoprostol, particularly at the recommended dose of 600 ug, for prevention of
      PPH during active management of labor. METHODS AND FINDINGS: We performed a
      double-blind, double-dummy randomized controlled non-inferiority trial between 23
      September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in
      Uganda. We randomized 1,140 women to receive 600 ug of misoprostol sublingually
      or 10 IU of oxytocin intramuscularly, along with matching placebos for the
      treatment they did not receive. Our primary outcome of interest was PPH, defined
      as measured blood loss >= 500 ml within 24 h of delivery. Secondary outcomes
      included measured blood loss >= 1,000 ml; mean measured blood loss at 1, 2, and
      24 h after delivery; death; requirement for blood transfusion; hemoglobin
      changes; and use of additional uterotonics. At 24 h postpartum, primary PPH
      occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%)
      participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05,
      p<0.001; absolute risk difference 11.2%, 95% CI 6.44 to 16.1). Severe PPH
      occurred in 20 (3.6%) and 15 (2.7%) participants in the misoprostol and oxytocin
      groups, respectively (RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk
      difference 0.9%, 95% CI -1.12 to 2.88). Mean measured blood loss was 341.5 ml
      (standard deviation [SD] 206.2) and 304.2 ml (SD 190.8, p = 0.002) at 2 h and
      484.7 ml (SD 213.3) and 432.8 ml (SD 203.5, p<0.001) at 24 h in the misoprostol
      and oxytocin groups, respectively. There were no significant differences between
      the two groups in any other secondary outcomes. Women in the misoprostol group
      more commonly experienced shivering (RR 1.91, 95% CI 1.65 to 2.21, p<0.001) and
      fevers (RR 5.20, 95% CI 3.15 to 7.21, p = 0.005). This study was conducted at a
      regional referral hospital with capacity for emergency surgery and blood
      transfusion. High-risk women were excluded from participation. CONCLUSIONS:
      Misoprostol 600 ug is inferior to oxytocin 10 IU for prevention of primary PPH in
      active management of labor. These data support use of oxytocin in settings where
      it is available. While not powered to do so, the study found no significant
      differences in rate of severe PPH, need for blood transfusion, postpartum
      hemoglobin, change in hemoglobin, or use of additional uterotonics between study
      groups. Further research should focus on clarifying whether and in which sub
      populations use of oxytocin would be preferred over sublingual misoprostol. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01866241 Please see later in the article for
      the Editors' Summary.

PMID- 25369201
TI  - CDO, an Hh-coreceptor, mediates lung cancer cell proliferation and tumorigenicity
      through Hedgehog signaling.
AB  - Hedgehog (Hh) signaling plays essential roles in various developmental processes,
      and its aberrant regulation results in genetic disorders or malignancies in
      various tissues. Hyperactivation of Hh signaling is associated with lung cancer
      development, and there have been extensive efforts to investigate how to control
      Hh signaling pathway and regulate cancer cell proliferation. In this study we
      investigated a role of CDO, an Hh co-receptor, in non-small cell lung cancer
      (NSCLC). Inhibition of Hh signaling by SANT-1 or siCDO in lung cancer cells
      reduced proliferation and tumorigenicity, along with the decrease in the
      expression of the Hh components. Histological analysis with NSCLC mouse tissue
      demonstrated that CDO was expressed in advanced grade of the cancer, and
      precisely co-localized with GLI1. These data suggest that CDO is required for
      proliferation and survival of lung cancer cells via Hh signaling. 

PMID- 25369202
TI  - Dynamical modeling of the cell cycle and cell fate emergence in Caulobacter
      crescentus.
AB  - The division of Caulobacter crescentus, a model organism for studying cell cycle
      and differentiation in bacteria, generates two cell types: swarmer and stalked.
      To complete its cycle, C. crescentus must first differentiate from the swarmer to
      the stalked phenotype. An important regulator involved in this process is CtrA,
      which operates in a gene regulatory network and coordinates many of the
      interactions associated to the generation of cellular asymmetry. Gaining insight
      into how such a differentiation phenomenon arises and how network components
      interact to bring about cellular behavior and function demands mathematical
      models and simulations. In this work, we present a dynamical model based on a
      generalization of the Boolean abstraction of gene expression for a minimal
      network controlling the cell cycle and asymmetric cell division in C. crescentus.
      This network was constructed from data obtained from an exhaustive search in the
      literature. The results of the simulations based on our model show a cyclic
      attractor whose configurations can be made to correspond with the current
      knowledge of the activity of the regulators participating in the gene network
      during the cell cycle. Additionally, we found two point attractors that can be
      interpreted in terms of the network configurations directing the two cell types.
      The entire network is shown to be operating close to the critical regime, which
      means that it is robust enough to perturbations on dynamics of the network, but
      adaptable to environmental changes. 

PMID- 25369204
TI  - Functionalized porous silicon surfaces as DESI-MS substrates for small molecules
      analysis.
AB  - In desorption electrospray ionization mass spectrometry (DESI-MS), the type of
      surface in addition to low gas and solvent flow rates help to avoid the
      "splashing of solvent" or "washing effect", by which samples are promptly removed
      from the surface by the spray. These effects operate on smooth surfaces and
      generally result in unstable signals as the spray moves over the spot. The aim of
      this work is to compare the performance of functionalized porous silicon surfaces
      (pSi) for small molecules analysis with regard to the stability of the signal and
      the limits of detection (LODs) observed in DESI-MS. The results showed that
      functional groups, like 1-decene and heptadecafluoro-1,1,2,2-tetrahydrodecyl
      trimethoxysilane, on pSi surface provides a good alternative for dried spot
      analysis by DESI-MS, improving stability of the signal and the LODs. This
      improvement is possible because the dual process containing the weak sample
      surface interactions of the hydrophobic characteristic of the functional groups
      and increasing the surface area of interaction between the sample and the thin
      solvent film created by the DESI spray, resulting in more effective dissolution
      of the analyte in the spray solvent without fast removal of the sample. 

PMID- 25369203
TI  - Defining disease phenotypes using national linked electronic health records: a
      case study of atrial fibrillation.
AB  - BACKGROUND: National electronic health records (EHR) are increasingly used for
      research but identifying disease cases is challenging due to differences in
      information captured between sources (e.g. primary and secondary care). Our
      objective was to provide a transparent, reproducible model for integrating these
      data using atrial fibrillation (AF), a chronic condition diagnosed and managed in
      multiple ways in different healthcare settings, as a case study. METHODS:
      Potentially relevant codes for AF screening, diagnosis, and management were
      identified in four coding systems: Read (primary care diagnoses and procedures),
      British National Formulary (BNF; primary care prescriptions), ICD-10 (secondary
      care diagnoses) and OPCS-4 (secondary care procedures). From these we developed a
      phenotype algorithm via expert review and analysis of linked EHR data from 1998
      to 2010 for a cohort of 2.14 million UK patients aged >= 30 years. The cohort was
      also used to evaluate the phenotype by examining associations between incident AF
      and known risk factors. RESULTS: The phenotype algorithm incorporated 286 codes:
      201 Read, 63 BNF, 18 ICD-10, and four OPCS-4. Incident AF diagnoses were recorded
      for 72,793 patients, but only 39.6% (N = 28,795) were recorded in primary care
      and secondary care. An additional 7,468 potential cases were inferred from data
      on treatment and pre-existing conditions. The proportion of cases identified from
      each source differed by diagnosis age; inferred diagnoses contributed a greater
      proportion of younger cases (<= 60 years), while older patients (>= 80 years)
      were mainly diagnosed in SC. Associations of risk factors (hypertension,
      myocardial infarction, heart failure) with incident AF defined using different
      EHR sources were comparable in magnitude to those from traditional consented
      cohorts. CONCLUSIONS: A single EHR source is not sufficient to identify all
      patients, nor will it provide a representative sample. Combining multiple data
      sources and integrating information on treatment and comorbid conditions can
      substantially improve case identification.

PMID- 25369205
TI  - Temporomandibular joint diagnostics using CBCT.
AB  - The present review will give an update on temporomandibular joint (TMJ) imaging
      using CBCT. It will focus on diagnostic accuracy and the value of CBCT compared
      with other imaging modalities for the evaluation of TMJs in different categories
      of patients; osteoarthritis (OA), juvenile OA, rheumatoid arthritis and related
      joint diseases, juvenile idiopathic arthritis and other intra-articular
      conditions. Finally, sections on other aspects of CBCT research related to the
      TMJ, clinical decision-making and concluding remarks are added. CBCT has emerged
      as a cost- and dose-effective imaging modality for the diagnostic assessment of a
      variety of TMJ conditions. The imaging modality has been found to be superior to
      conventional radiographical examinations as well as MRI in assessment of the TMJ.
      However, it should be emphasized that the diagnostic information obtained is
      limited to the morphology of the osseous joint components, cortical bone
      integrity and subcortical bone destruction/production. For evaluation of soft
      tissue abnormalities, MRI is mandatory. There is an obvious need for research on
      the impact of CBCT examinations on patient outcome. 

PMID- 25369207
TI  - Surgical treatment of pediatric rhinosinusitis.
AB  - Pediatric rhinosinusitis is a common sequela of upper respiratory infections in
      children. It is usually a self-limited disease, sometimes requiring antibiotic
      therapy. Surgery may be indicated in children who suffer complication of acute
      rhinosinusitis, severe recurrent acute rhinosinusitis, rhinosinusitis in cystic
      fibrosis with or without polyposis, chronic rhinosinusitis refractory to maximal
      medical management, allergic fungal sinusitis, and paranasal sinus mucoceles.
      Surgical options include, adenoidectomy, sinus puncture and lavage, open surgical
      approaches, endoscopic sinus surgery, balloon sinuplasty, and turbinectomy or
      turbinate reduction. This paper reviews the anatomy and physiology of
      rhinosinusitis in children and current knowledge of the indications and best
      methods of surgical treatment. 

PMID- 25369206
TI  - An interaction between a FNDC5 variant and obesity modulates glucose metabolism
      in a Chinese Han population.
AB  - BACKGROUND: To investigate the impact of common variants of FNDC5 on type 2
      diabetes and clinical traits related to glucose metabolism in a large Chinese
      population sample. METHODS: Three tagging single nucleotide polymorphisms within
      the region of the FNDC5 gene were selected and genotyped in 6822 participants.
      Detailed clinical investigations and biochemistry measurements were carried out
      in all of the participants. Subjects without diabetes were classified into normal
      weight and overweight/obese subgroups according to body mass index (BMI).
      RESULTS: None of the SNPs were associated with either the risk of type 2 diabetes
      in all of the participants or with any of the clinical quantitative traits in the
      controls with normal glucose regulation. Subgroup analysis showed that in
      controls with normal weight (BMI <25 kg/m(2)), the rs16835198 major allele G was
      significantly associated with fasting insulin levels, and that each additional
      copy of the allele resulted in a 0.0178 mU/L increment of the values (p = 0.046).
      Moreover, after adjusting for confounding variables, there were trends towards
      correlation of rs16835198 with HOMA-insulin resistance (HOMA-IR) (p = 0.057) and
      low-density lipoprotein cholesterol (LDL-C) levels (p = 0.083). In
      overweight/obese subjects (BMI >= 25 Kg/m(2)), we noted rs16835198 showed trends
      towards association with fasting insulin (p = 0.057) and HOMA-IR levels (p =
      0.091), both of which declined with additional copies of the major allele G.
      Moreover, rs16835198 was significantly associated with high-density lipoprotein
      cholesterol (HDL-C) levels (p = 0.013), and HOMA-beta cell function (p = 0.028)
      in the overweight/obese subjects. Finally, we observed a significant interaction
      between BMI-rs16835198 and fasting insulin levels in the control group (p =
      0.003). CONCLUSIONS: Our data indicate that the effect of the common FNDC5 SNP
      rs16835198 on fasting insulin was significantly modified by BMI in the Chinese
      Han population.

PMID- 25369208
TI  - Dose-dependent effects of the clinical anesthetic isoflurane on Octopus vulgaris:
      a contribution to cephalopod welfare.
AB  - Recent progress in animal welfare legislation relating to invertebrates has
      provoked interest in methods for the anesthesia of cephalopods, for which
      different approaches to anesthesia have been tried but in most cases without
      truly anesthetizing the animals. For example, several workers have used muscle
      relaxants or hypothermia as forms of "anesthesia." Several inhalational
      anesthetics are known to act in a dose-dependent manner on the great pond snail
      Lymnaea stagnalis, a pulmonate mollusk. Here we report, for the first time, on
      the effects of clinical doses of the well-known inhalational clinical anesthetic
      isoflurane on the behavioral responses of the common octopus Octopus vulgaris. In
      each experiment, isoflurane was equilibrated into a well-aerated seawater bath
      containing a single adult O. vulgaris. Using a web camera, we recorded each
      animal's response to touch stimuli eliciting withdrawal of the arms and siphon
      and observed changes in the respiratory rate and the chromatophore pattern over
      time (before, during, and after application of the anesthetic). We found that
      different animals of the same size responded with similar behavioral changes as
      the isoflurane concentration was gradually increased. After gradual application
      of 2% isoflurane for a maximum of 5 min (at which time all the responses
      indicated deep anesthesia), the animals recovered within 45-60 min in fresh
      aerated seawater. Based on previous findings in gastropods, we believe that the
      process of anesthesia induced by isoflurane is similar to that previously
      observed in Lymnaea. In this study we showed that isoflurane is a good,
      reversible anesthetic for O. vulgaris, and we developed a method for its use.

PMID- 25369209
TI  - Identification of novel factors involved in modulating motility of Salmonella
      enterica serotype typhimurium.
AB  - Salmonella enterica serotype Typhimurium can move through liquid using swimming
      motility, and across a surface by swarming motility. We generated a library of
      targeted deletion mutants in Salmonella Typhimurium strain ATCC14028, primarily
      in genes specific to Salmonella, that we have previously described. In the work
      presented here, we screened each individual mutant from this library for the
      ability to move away from the site of inoculation on swimming and swarming
      motility agar. Mutants in genes previously described as important for motility,
      such as flgF, motA, cheY are do not move away from the site of inoculation on
      plates in our screens, validating our approach. Mutants in 130 genes, not
      previously known to be involved in motility, had altered movement of at least one
      type, 9 mutants were severely impaired for both types of motility, while 33
      mutants appeared defective on swimming motility plates but not swarming motility
      plates, and 49 mutants had reduced ability to move on swarming agar but not
      swimming agar. Finally, 39 mutants were determined to be hypermotile in at least
      one of the types of motility tested. Both mutants that appeared non-motile and
      hypermotile on plates were assayed for expression levels of FliC and FljB on the
      bacterial surface and many of them had altered levels of these proteins. The
      phenotypes we report are the first phenotypes ever assigned to 74 of these open
      reading frames, as they are annotated as 'hypothetical genes' in the Typhimurium
      genome. 

PMID- 25369211
TI  - Feeding and dispersal behavior of the cotton leafworm, Alabama argillacea
      (Hubner) (Lepidoptera: Noctuidae), on Bt and non-Bt cotton: implications for
      evolution and resistance management.
AB  - The host acceptance of neonate Alabama argillacea (Hubner) (Lepidoptera:
      Noctuidae) larvae to Bt cotton plants exerts a strong influence on the potential
      risk that this pest will develop resistance to Bt cotton. This will also
      determine the efficiency of management strategies to prevent its resistance such
      as the "refuge-in-the-bag" strategy. In this study, we assessed the acceptance of
      neonate A. argillacea larvae to Bt and non-Bt cotton plants at different
      temperatures during the first 24 h after hatching. Two cotton cultivars were used
      in the study, one a Bt DP 404 BG (Bollgard) cultivar, and the other, an
      untransformed isoline, DP 4049 cultivar. There was a greater acceptance by live
      neonate A. argillacea larvae for the non-Bt cotton plants compared with the Bt
      cotton plants, especially in the time interval between 18 and 24 h. The
      percentages of neonate A. argillacea larvae found on Bt or non-Bt plants were
      lower when exposed to temperatures of 31 and 34  degrees C. The low acceptance of
      A. argillacea larvae for Bt cotton plants at high temperatures stimulated the
      dispersion of A. argillacea larvae. Our results support the hypothesis that the
      dispersion and/or feeding behavior of neonate A. argillacea larvae is different
      between Bt and non-Bt cotton. The presence of the Cry1Ac toxin in Bt cotton
      plants, and its probable detection by the A. argillacea larvae tasting or eating
      it, increases the probability of dispersion from the plant where the larvae
      began. These findings may help to understand how the A. argillacea larvae detect
      the Cry1Ac toxin in Bt cotton and how the toxin affects the dispersion behavior
      of the larvae over time. Therefore, our results are extremely important for the
      management of resistance in populations of A. argillacea on Bt cotton.

PMID- 25369212
TI  - In-situ calibration of clinical built-in KAP meters with traceability to a
      primary standard using a reference KAP meter.
AB  - The air kerma-area product (KAP) is used for settings of diagnostic reference
      levels. The International Atomic Energy Agency (IAEA) recommends that doses in
      diagnostic radiology (including the KAP values) be estimated with an accuracy of
      at least +/- 7% (k = 2). Industry standards defined by the International
      Electrotechnical Commission (IEC) specify that the uncertainty of KAP meter
      measurements should be less than +/- 25% (k = 2). Medical physicists willing to
      comply with the IAEA's recommendation need to apply correction factors to KAP
      values reported by x-ray units. The aim of this work is to present and evaluate a
      calibration method for built-in KAP meters on clinical x-ray units. The method is
      based on (i) a tandem calibration method, which uses a reference KAP meter
      calibrated to measure the incident radiation, (ii) measurements using an energy
      independent ionization chamber to correct for the energy dependence of the
      reference KAP meter, and (iii) Monte Carlo simulations of the beam quality
      correction factors that correct for differences between beam qualities at a
      standard laboratory and the clinic. The method was applied to the KAP meter in a
      Siemens Aristos FX plus unit. It was found that values reported by the built-in
      KAP meter differed from the more accurate values measured by the reference KAP
      meter by more than 25% for high tube voltages (more than 140 kV) and heavily
      filtered beams (0.3 mm Cu). Associated uncertainties were too high to claim that
      the IEC's limit of 25% was exceeded. Nevertheless the differences were high
      enough to justify the need for a more accurate calibration of built-in KAP
      meters.

PMID- 25369210
TI  - A nuclear factor of high mobility group box protein in Toxoplasma gondii.
AB  - High mobility group box 1 (HMGB1) is a nuclear factor that usually binds DNA and
      modulates gene expression in multicellular organisms. Three HMGB1 orthologs were
      predicted in the genome of Toxoplasma gondii, an obligate intracellular protozoan
      pathogen, termed TgHMGB1a, b and c. Phylogenetic and bioinformatic analyses
      indicated that these proteins all contain a single HMG box and which shared in
      three genotypes. We cloned TgHMGB1a, a 33.9 kDa protein that can stimulates
      macrophages to release TNF-alpha, and, we demonstrated that the TgHMGB1a binds
      distorted DNA structures such as cruciform DNA in electrophoretic mobility shift
      assays (EMSA). Immunofluorescence assay indicated TgHMGB1a concentrated in the
      nucleus of intracellular tachyzoites but translocated into the cytoplasm while
      the parasites release to extracellular. There were no significant phenotypic
      changes when the TgHMGB1a B box was deleted, while transgenic parasites that
      overexpressed TgHMGB1a showed slower intracellular growth and caused delayed
      death in mouse, further quantitative RT-PCR analyses showed that the expression
      levels of many important genes, including virulence factors, increased when
      TgHMGB1a was overexpressed, but no significant changes were observed in TgHMGB1a
      B box-deficient parasites. Our findings demonstrated that TgHMGB1a is indeed a
      nuclear protein that maintains HMG box architectural functions and is a potential
      proinflammatory factor during the T.gondii infection. Further studies that
      clarify the functions of TgHMGB1s will increase our knowledge of transcriptional
      regulation and parasite virulence, and might provide new insight into host
      parasite interactions for T. gondii infection. 

PMID- 25369213
TI  - The symptom burden of treatment-naive patients with head and neck cancer.
AB  - BACKGROUND: The treatment of head and neck cancer (HNC) may cause substantial
      local and systemic symptomatic morbidities, but many patients have high symptom
      levels before treatment begins. Knowledge of disease-related (treatment-naive)
      symptom status would aid in the evaluation of the symptomatic benefit or burden
      of HNC therapies. METHODS: The authors retrospectively examined symptoms, quality
      of life, and health status reported by patients with HNC who were naive to any
      treatment. Symptoms were explored by anatomical site and disease factors were
      correlated with symptom severity and interference. A clustering algorithm was
      used to identify a subset of highly symptomatic patients, and the effects of
      disease site, tumor stage, and demographic variables on membership in this high
      symptom group were examined. RESULTS: A total of 748 treatment-naive patients
      with mucosal (434 patients), nonmucosal (272 patients), or skull base (42
      patients) tumors were identified who had rated their symptoms using the MD
      Anderson Symptom Inventory. The majority of patients were white non-Hispanic
      (82%) and male (68%), with a median age of 59 years. Approximately one-third the
      patients had a high pretreatment symptom burden. Pain, fatigue, distress, and
      disturbed sleep were the most severe symptoms reported, regardless of tumor stage
      or site. Symptom burden was found to be higher among patients with more advanced
      disease. Predictors of a high symptom burden included having a mucosal tumor and
      being female. CONCLUSIONS: The high prevalence of moderate to severe symptoms
      found in the current study demonstrates the importance of assessing patient
      reported symptoms routinely before treatment is initiated and emphasizes the need
      for symptom management in parallel with disease treatment. Baseline
      characterization of symptom status should be incorporated into clinical trials
      that may affect symptom burden.

PMID- 25369214
TI  - Investigating thiol-modification on hyaluronan via carbodiimide chemistry using
      response surface methodology.
AB  - Hyaluronan (HA) is a naturally occurring glycosaminoglycan widely researched for
      its use as a biomaterial in tissue engineering, drug delivery, angiogenesis, and
      ophthalmic surgeries. The mechanical properties of this biomaterial can be
      altered to a required extent by chemically modifying the pendant reactive groups.
      However, derivatizing these polymers to a predetermined extent has been the
      Achilles heel for this process. In this study, we have investigated the factors
      controlling the derivatization of the carboxyl moieties of HA with amine
      containing thiol, cystamine dihydrochloride (Cys), via carbodiimide crosslinking
      chemistry. We used fractional factorial design to screen and identify the
      significant factor(s) affecting the reaction, and response surface methodology
      (RSM) to develop a model equation for predicting the degree of thiolation of HA.
      Also, we analyzed the reaction mechanism for potential side reactions. We
      observed that N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)
      (mole ratio with repeat unit of HA) is the significant factor controlling the
      degree of amidation. The quadratic equations developed from RSM predict the
      formulation for a desired degree of amidation of HA and percentage of potential
      side product. Hence, derivatizing HA to a predetermined extent with minimal side
      product can be achieved using the statistical design of experiments.

PMID- 25369215
TI  - Redefining genomic privacy: trust and empowerment.
AB  - Fulfilling the promise of the genetic revolution requires the analysis of large
      datasets containing information from thousands to millions of participants.
      However, sharing human genomic data requires protecting subjects from potential
      harm. Current models rely on de-identification techniques in which privacy versus
      data utility becomes a zero-sum game. Instead, we propose the use of trust
      enabling techniques to create a solution in which researchers and participants
      both win. To do so we introduce three principles that facilitate trust in genetic
      research and outline one possible framework built upon those principles. Our hope
      is that such trust-centric frameworks provide a sustainable solution that
      reconciles genetic privacy with data sharing and facilitates genetic research. 

PMID- 25369216
TI  - Rational design of pH-controlled DNA strand displacement.
AB  - Achieving strategies to finely regulate with biological inputs the formation and
      functionality of DNA-based nanoarchitectures and nanomachines is essential toward
      a full realization of the potential of DNA nanotechnology. Here we demonstrate an
      unprecedented, rational approach to achieve control, through a simple change of
      the solution's pH, over an important class of DNA association-based reactions. To
      do so we took advantage of the pH dependence of parallel Hoogsteen interactions
      and rationally designed two triplex-based DNA strand displacement strategies that
      can be triggered and finely regulated at either basic or acidic pHs. Because pH
      change represents an important input both in healthy and pathological biological
      pathways, our findings can have implication for the development of DNA
      nanostructures whose assembly and functionality can be triggered in the presence
      of specific biological targets. 

PMID- 25369218
TI  - Recognition and management of rodent-borne infectious disease outbreaks after
      heavy rainfall and flooding.
AB  - Climatic events, especially heavy rains and flooding following periods of
      relative drought, have precipitated both arthropod-borne and rodent-borne
      infectious disease outbreaks. Heavy rainfall encourages excessive wild grass seed
      production that supports increased outdoor rodent populations, and flooding
      forces rodents from their burrows near water sources into the built environment
      and closer to humans. The objectives of this review are to alert clinicians to
      the climatic conditions common to hurricane-prone regions, such as Louisiana,
      that can precipitate outbreaks of the two rodent-borne diseases most often
      associated with periods of heavy rainfall and flooding, leptospirosis (LS) and
      hantavirus pulmonary syndrome (HPS). It will also describe the epidemiology,
      presenting clinical manifestations and outcomes of these rodent-borne infectious
      diseases, and recommend both prophylactic therapies and effective control and
      prevention strategies for rodent-borne infectious disease outbreaks. Healthcare
      providers should maintain high levels of suspicion for LS in patients developing
      febrile illnesses after contaminated freshwater exposures during flooding or
      recreational events, and for HPS in patients with febrile illnesses that progress
      rapidly to respiratory failure following rodent exposures in enclosed spaces.
      Public health educational strategies should encourage limiting human contact with
      all wild and peridomestic rats and mice, avoiding all contact with rodent
      excreta, safely disposing of all rodent excreta, and modifying the built
      environment to deter rodents from colonizing households and workplaces. 

PMID- 25369219
TI  - Dysplastic cerebellar gangliocytoma lhermitte-duclos disease imaging and magnetic
      resonance spectroscopy.
AB  - Lhermitte-Duclos disease (LDD) is a rare, benign, slow-growing, unilateral mass
      of the cerebellar cortex. Our case is that of a 71-year-old male with a superior
      cerebellar lesion consistent with LDD on imaging and Magnetic Resonance
      Spectroscopy (MRS). It has been reported that MRS can be a valuable diagnostic
      addition, as it allows for a non-invasive diagnosis and analysis to distinguish a
      benign lesion, such as an intraparenchymal lesion, and in our case, from a true
      neoplastic lesion. 

PMID- 25369220
TI  - Spontaneous rectus sheath hematoma: two variant cases.
AB  - We present two variant cases of spontaneous rectus sheath hematoma (SRSH). A 71
      year-old woman presented with ST elevation myocardial infarction and was found to
      have multivessel coronary artery disease. She was treated with aspirin,
      clopidogrel, eptifibatide, and heparin. Heparin was continued while preoperative
      workup for coronary artery bypass grafting was done. She developed a large 20x10
      cm actively bleeding SRSH while on heparin. It was surgically evacuated. The
      second case represents an atypical cause of SRSH. A 64-year-old woman with
      Wegener's Granulomatosis presented with anemia and abdominal pain. Abdominal CT
      showed a large 22 cm SRSH without active bleeding that was treated
      conservatively. Both patients did well on follow-up. The incidence of SRSH is
      likely to increase in the coming years with the increasing use of antithrombotic
      agents for many disease processes. Clinicians should be aware of typical and
      atypical presentations of SRSH and its variant management options. 

PMID- 25369221
TI  - Bisphosphonate-related osteonecrosis of the jaw.
AB  - Although there has been a growing body of literature about bisphosphonates since
      1969, it was not until 2003 that treatment with this medication was associated
      with osteonecrosis of the jaw. Presented herein is such a case. 

PMID- 25369222
TI  - Aberrant left main bile duct draining directly into the cystic duct or
      gallbladder: an unreported anatomical variation and cause of bile duct injury
      during laparoscopic cholecystectomy.
AB  - Despite recent advances, iatrogenic bile duct injury remains one of the most
      common complications of laparoscopic cholecystectomy. Aberrant biliary tract
      anatomy is one of the major risk factors for iatrogenic bile duct injury. In this
      case report, for the first time, we report a case of aberrant left main bile duct
      draining directly into the cystic duct or gallbladder that presented with bile
      duct injury after laparoscopic cholecystectomy. We hope that the diagnostic and
      management approach used in this case will help physicians to identify and manage
      their patients should they face such a rare anatomy. 

PMID- 25369223
TI  - Portal-endocrine and gastric-exocrine drainage technique of pancreas
      transplantation provides an easy access for evaluation of pancreatic allograft
      dysfunction: six-year experience at a single center.
AB  - BACKGROUND: The aim of this study is to report our six-year experience with
      portal-endocrine and gastric-exocrine drainage technique of pancreatic
      transplantation, which was first developed and implemented at our center in 2007.
      METHODS: In this study, the outcomes of all patients at our center who had
      pancreas transplantation with portal-endocrine and gastric-exocrine drainage
      technique were evaluated. RESULTS: From October 2007 to November 2013, 38
      patients had pancreas transplantation with this technique - 31 simultaneous
      kidney pancreas and seven pancreas alone. Median duration of follow-up was 3.8
      years. One-, three-, and five-year patient and graft survival rates were 94%,
      87%, 70% and 83%, 65%, 49%, respectively. For pancreas allograft dysfunction
      evaluation, 51 upper endoscopies were performed in 14 patients; donor duodenal
      biopsies were successfully obtained in 45 (88%). We detected nine episodes of
      acute rejection (eight patients) and seven episodes of cytomegalovirus (CMV)
      duodenitis (six patients). No patient developed any complication due to upper
      endoscopy. CONCLUSIONS: Portal-endocrine and gastric-exocrine drainage technique
      of pancreas transplantation provides lifelong easy access to the transplanted
      duodenum for evaluation of pancreatic allograft dysfunction.

PMID- 25369224
TI  - Atypical mycobacterial infections of peritoneal dialysis catheter exit sites--a
      Louisiana issue.
AB  - Exit-site infections involving peritoneal dialysis catheters are a cumbersome
      issue that can be difficult to manage. Such infections are usually due to gram
      positive organisms and are often treated successfully with oral and/or topical
      antibiotics. Infections associated with Mycobacterium sp. are much more rare and
      difficult to treat. We report our experience with four cases of exit-site
      infections with Mycobacterium sp. in the New Orleans area, along with a review of
      risk factors and current literature. 

PMID- 25369225
TI  - Protecting the private practice of medicine: direct primary care--Louisiana
      poised to lead.

PMID- 25369226
TI  - ECG Case of the Month. ECG in a 49-Year-Old Man With Chest Pain. DIAGNOSIS: Sinus
      rhythm (rate, 97 beats/min); two episodes of AV dissociation with an accelerated
      idioventricular rhythm (rate, 103 beats/min) dissociated from sinus rhythm; the
      two rhythms produce numerous fusion QRS complexes; acute inferoposterior
      myocardial infaraction; left atrial enlargement.

PMID- 25369227
TI  - Radiology case of the month. Abnormally dilated arteries in an asymptomatic male.
      RADIOLOGIC DIAGNOSIS: Aortic coarctation. There is narrowing in the region of the
      aortic isthmus (arrows, Figures 2 and 4). The extent of collateral arterial
      dilation (arrows, Figures 1 and 3) suggests this to be a hemodynamically
      significant finding.
AB  - A 61-year-old male with a past medical history of chronic, uncontrolled
      hypertension received a non-contrasted computed tomogram (CT) of the chest and
      abdomen to investigate for possible Conn syndrome. This noncontrast study showed
      some areas of nodularity around the vertebral bodies bilaterally and extending
      into the posterior mediastinal region. A CT of the chest with intravenous
      contrast, and 3D reconstruction were then obtained. 

PMID- 25369228
TI  - Clinical case of the month: a 22-year-old man with AIDS presenting with shortness
      of breath and an oral lesion.
AB  - Since the development of combination antiretroviral therapy (cART), the incidence
      and mortality associated with Kaposi sarcoma (KS) have been reduced, although not
      eliminated. Clinical presentations of KS range from simple skin involvement to
      disseminated disease, including involvement of the oral cavity and viscera, which
      portends a more ominous prognosis. Multiple case reports and data from clinical
      trials indicate that administration of systemic corticosteroids may aggravate KS.
      We present a case of disseminated KS following administration of prednisone for
      presumed immune reconstitution inflammatory syndrome (IRIS) associated with
      fungal pneumonia in an HIV-infected individual. The discussion that follows
      outlines the pathophysiology and clinical presentations associated with KS and
      existing data for the role of corticosteroids in promoting KS progression. 

PMID- 25369229
TI  - Pathology image of the month: death in a young adult with sickle cell disease.
AB  - A 27-year-old African-American female with known sickle cell disease was admitted
      for sickle cell crisis and presumed sepsis. The patient's past medical history
      was complicated by multiple sickle cell-related complications, including seizures
      and multiple prior blood transfusions. Her hospital course included
      Staphylococcus epidermidis bacteremia, for which broad spectrum antibiotics were
      prescribed. On hospital day nine, the patient was found unresponsive and declared
      dead after unsuccessful efforts at resuscitation. An unlimited autopsy
      examination was conducted under authorization of the coroner. Findings included
      numerous pathologic features ascribed to sickle cell disease, including systemic
      siderosis and splenic atrophy [weight 10 gm (140+/-78)], fibrosis, and Gamna
      Gandy nodules. Additional autopsy findings included cardiomegaly with a heart
      weight of 450 gm (312+/-78), right atrial and right ventricular chamber
      dilatation, and hepatomegaly with a liver weight of 2650 gm (1475+/-362). The
      image below demonstrates microscopic examination of the lung parenchyma.

PMID- 25369230
TI  - Identification of peptidoglycan-associated proteins as vaccine candidates for
      enterococcal infections.
AB  - Infections by opportunistic bacteria have significant contributions to morbidity
      and mortality of hospitalized patients and also lead to high expenses in
      healthcare. In this setting, one of the major clinical problems is caused by Gram
      positive bacteria such as enterococci and staphylococci. In this study we
      extract, purify, identify and characterize immunogenic surface-exposed proteins
      present in the vancomycin resistant enterococci (VRE) strain Enterococcus faecium
      E155 using three different extraction methods: trypsin shaving, biotinylation and
      elution at high pH. Proteomic profiling was carried out by gel-free and gel
      nanoLC-MS/MS analyses. The total proteins found with each method were 390 by the
      trypsin shaving, 329 by the elution at high pH, and 45 using biotinylation. An
      exclusively extracytoplasmic localization was predicted in 39 (10%) by trypsin
      shaving, in 47 (15%) by elution at high pH, and 27 (63%) by biotinylation.
      Comparison between the three extraction methods by Venn diagram and subcellular
      localization predictors (CELLO v.2.5 and Gpos-mPLoc) allowed us to identify six
      proteins that are most likely surface-exposed: the SCP-like extracellular
      protein, a low affinity penicillin-binding protein 5 (PBP5), a basic membrane
      lipoprotein, a peptidoglycan-binding protein LysM (LysM), a D-alanyl-D-alanine
      carboxypeptidase (DdcP) and the peptidyl-prolyl cis-trans isomerase (PpiC). Due
      to their close relationship with the peptidoglycan, we chose PBP5, LysM, DdcP and
      PpiC to test their potential as vaccine candidates. These putative surface
      exposed proteins were overexpressed in Escherichia coli and purified. Rabbit
      polyclonal antibodies raised against the purified proteins were able to induce
      specific opsonic antibodies that mediated killing of the homologous strain E.
      faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis
      12030, type 2 and type 5. Passive immunization with rabbit antibodies raised
      against these proteins reduced significantly the colony counts of E. faecium E155
      in mice, indicating the effectiveness of these surface-related proteins as
      promising vaccine candidates to target different enterococcal pathogens. 

PMID- 25369231
TI  - Cytotoxicity and gene expression in sarcoma 180 cells in response to spiky
      magnetoplasmonic supraparticles.
AB  - Multifunctional nanoparticles (NPs) have been designed for a variety of cell
      imaging and therapeutic applications, and the study of their cellular
      interactions is crucial to the development of more efficient biomedical
      applications. Among current nanomaterials, concave core-shell NPs with complex
      angled geometries are attractive owing to their unique shape-dependent optical
      and physical properties as well as different tendency for cell interaction. In
      this study, we investigated the morphology effect of spiky gold-coated iron oxide
      supraparticles (Fe3O4@Au SPs) on cytotoxicity and global gene expression in
      sarcoma 180 cells. Cells treated for 7 days with spiky supraparticles (SPs) at
      concentrations up to 50 MUg/mL showed >90% viability, indicating that these NPs
      were nontoxic. To shed light on the differences in cytotoxicity, we monitored the
      expression of 33,315 genes using microarray analysis of SP-treated cells. The 171
      up-regulated genes and 181 down-regulated genes in spiky SP-treated cells
      included Il1b, Spp1, Il18, Rbp4, and Il11ra1, where these genes are mainly
      involved in cell proliferation, differentiation, and apoptosis. These results
      suggested that the spiky Fe3O4@Au SPs can induce noncytotoxicity and gene
      expression in tumor cells, which may be a promising cornerstone on which to base
      related research such as cyto-/genotoxicology of nanomaterials or the design of
      nanoscale drug carriers.

PMID- 25369232
TI  - Six-coordinate nitrito and nitrato complexes of manganese porphyrin.
AB  - Reaction of small increments of NO2 gas with sublimed amorphous layers of
      Mn(II)(TPP) (TPP = meso-tetra-phenylporphyrinato dianion) in a vacuum cryostat
      leads to formation of the 5-coordinate monodentate nitrato complex
      Mn(III)(TPP)(eta(1)-ONO2) (II). This transformation proceeds through the two
      distinct steps with initial formation of the five coordinate O-nitrito complex
      Mn(III)(TPP)(eta(1)-ONO) (I) as demonstrated by the electronic absorption spectra
      and by FTIR spectra using differently labeled nitrogen dioxide. A plausible
      mechanism for the second stage of reaction is offered based on the spectral
      changes observed upon subsequent interaction of (15)NO2 and NO2 with the layered
      Mn(TPP). Low-temperature interaction of I and II with the vapors of various
      ligands L (L = O-, S-, and N-donors) leads to formation of the 6-coordinate O
      nitrito Mn(III)(TPP)(L)(eta(1)-ONO) and monodentate nitrato
      Mn(III)(TPP)(L)(eta(1)-ONO2) complexes, respectively. Formation of the 6
      coordinate O-nitrito complex is accompanied by the shifts of the nu(N?O) band to
      lower frequency and of the nu(N-O) band to higher frequency. The frequency
      difference between these bands Deltanu = nu(N?O) - nu(N-O) is a function of L and
      is smaller for the stronger bases. Reaction of excess NH3 with I leads to
      formation of Mn(TPP)(NH3)(eta(1)-ONO) and of the cation [Mn(TPP)(NH3)2](+) plus
      ionic nitrite. The nitrito complexes are relatively unstable, but several of the
      nitrato species can be observed in the solid state at room temperature. For
      example, the tetrahydrofuran complex Mn(TPP)(THF)(eta(1)-ONO2) is stable in the
      presence of THF vapors (~5 mm), but it loses this ligand upon high vacuum pumping
      at RT. When L = dimethylsulfide (DMS), the nitrato complex is stable only to ~-30
      degrees C. Reactions of II with the N-donor ligands NH3, pyridine, or 1
      methylimidazole are more complex. With these ligands, the nitrato complexes
      Mn(III)(TPP)(L)(eta(1)-ONO2) and the cationic complexes [Mn(TPP)(L)2](+) coexist
      in the layer at room temperature, the latter formed as a result of NO3(-)
      displacement when L is in excess. 

PMID- 25369234
TI  - Cupulin is a zona pellucida-like domain protein and major component of the cupula
      from the inner ear.
AB  - The extracellular membranes of the inner ear are essential constituents to
      maintain sensory functions, the cupula for sensing torsional movements of the
      head, the otoconial membrane for sensing linear movements and accelerations like
      gravity, and the tectorial membrane in the cochlea for hearing. So far a number
      of structural proteins have been described, but for the gelatinous cupula precise
      data are missing. Here, we describe for the first time a major proteinogenic
      component of the cupula structure with an apparent molecular mass of 45 kDa from
      salmon. Analyses of respective peptides revealed highly conserved amino-acid
      sequences with identity to zona pellucida-like domain proteins.
      Immunohistochemistry studies localized the protein in the ampulla of the inner
      ear from salmon and according to its anatomical appearance we identified this
      glycoprotein as Cupulin. Future research on structure and function of zona
      pellucida-like domain proteins will enhance our knowledge of inner ear diseases,
      like sudden loss of vestibular function and other disturbances. 

PMID- 25369235
TI  - Effects of bisphenol S on the structures and activities of trypsin and pepsin.
AB  - The effects of bisphenol S on the structures and activities of trypsin and pepsin
      were investigated by various methods like UV-visible absorbance, fluorescence,
      circular dichroism, and molecular docking. The secondary and tertiary structures
      of trypsin and pepsin were altered by bisphenol S binding, which resulted in the
      loosening of the skeletons of trypsin and pepsin. In addition, bisphenol S
      induced microenvironmental changes around tyrosine and tryptophan residues of
      trypsin and pepsin. The activity experimental results showed that the activity of
      pepsin decreases obviously with the increasing concentration of BPS, while the
      activity of trypsin does not change remarkably. The binding and thermodynamic
      parameters obtained by molecular docking and fluorescence spectroscopy showed
      that the bindings of bisphenol S to trypsin and pepsin were spontaneous processes
      and hydrogen bonding and hydrophobic interactions played a vital role in
      stabilizing the bisphenol S-trypsin and bisphenol S-pepsin complexes. The binding
      constants (K(A)) of bisphenol S with trypsin were 7.42 * 10(4) (298 K) and 5.91 *
      10(4) L/mol (310 K), and those of pepsin were 5.78 * 10(4) (298 K) and 4.44 *
      10(4) L/mol (310 K). Moreover, there was one main kind of binding site for
      bisphenol S on trypsin or pepsin.

PMID- 25369236
TI  - Perceptions of the roles of behaviour and genetics in disease risk: are they
      associated with behaviour change attempts.
AB  - The aims of the present study were to (i) examine the prevalence of perceived
      behavioural and genetic causal beliefs for four chronic conditions (i.e. obesity,
      heart disease, diabetes and cancer); (ii) to examine the association between
      these causal beliefs and attempts at behaviour change (i.e. physical activity,
      weight management, fruit intake, vegetable intake and soda intake). The data come
      from the Health Information National Trends Survey, a nationally representative
      population-based survey of adults (N = 3407). Results indicated that participants
      held both behavioural and genetic causal beliefs for all four chronic conditions.
      Multivariate analyses indicated that behavioural causal beliefs were
      significantly associated with attempts to increase physical activity and
      vegetable intake and to decrease weight. Genetic causal beliefs for cancer were
      significantly associated with reported attempts to maintain weight. Behaviour and
      genetic causal beliefs were not associated with changes in either fruit or soda
      intake. In conclusion, while behavioural causal beliefs are associated with
      behavioural change, measurement must capture disease-specific behavioural causal
      beliefs as they are associated with different health behaviours.

PMID- 25369237
TI  - Age is a critical risk factor for severe fever with thrombocytopenia syndrome.
AB  - BACKGROUND: Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging
      infectious disease in East Asia. SFTS is a tick borne hemorrhagic fever caused by
      SFTSV, a new bunyavirus named after the syndrome. We investigated the
      epidemiology of SFTS in Laizhou County, Shandong Province, China. METHODS: We
      collected serum specimens of all patients who were clinically diagnosed as
      suspected SFTS cases in 2010 and 2011 in Laizhou County. The patients' serum
      specimens were tested for SFTSV by real time fluorescence quantitative PCR (RT
      qPCR). We collected 1,060 serum specimens from healthy human volunteers by random
      sampling in Laizhou County in 2011. Healthy persons' serum specimens were tested
      for specific SFTSV IgG antibody by ELISA. RESULTS: 71 SFTS cases were diagnosed
      in Laizhou County in 2010 and 2011, which resulted in the incidence rate of
      4.1/100,000 annually. The patients ranged from 15 years old to 87 years old and
      the median age of the patients were 59 years old. The incidence rate of SFTS was
      significantly higher in patients over 40 years old and fatal cases only occurred
      in patients over 50 years old. 3.3% (35/1,060) of healthy people were positive to
      SFTSV IgG antibody. The SFTSV antibody positive rate was not significantly
      different among people at different age groups. CONCLUSION: Our results revealed
      that seroprevalence of SFTSV in healthy people in Laizhou County was not
      significantly different among age groups, but SFTS patients were mainly elderly
      people, suggesting that age is the critical risk factor or determinant for SFTS
      morbidity and mortality.

PMID- 25369238
TI  - Human herpesvirus 6 involvement in paediatric drug hypersensitivity syndrome.
AB  - BACKGROUND: Human herpesvirus (HHV)6 positivity in the context of drug
      hypersensitivity syndrome (DHS) may influence disease severity. Systemic
      corticosteroid treatment of those with DHS testing positive for HHV6 has been
      speculated to prolong the duration of disease. OBJECTIVES: To evaluate whether
      paediatric HHV6-positive patients with DHS develop a more severe illness than
      those without presumed reactivation, and to evaluate the response to systemic
      corticosteroid treatment. METHODS: A retrospective case series of 29 paediatric
      inpatients treated for DHS and tested for HHV6 was undertaken. HHV6-positive and 
      negative patients were identified and stratified into groups treated or not
      treated with systemic corticosteroids to examine their disease severity on the
      basis of hospital length of stay (LOS), total number of febrile days (Tfeb) and
      days until cessation of progression (CTP). RESULTS: Human herpesvirus6-positive
      patients had similar demographic characteristics to those of HHV6-negative
      patients, but had significantly longer hospital LOS (11.5 days vs. 5 days, P =
      0.039), Tfeb (12.5 days vs. 3 days, P = 0.032) and CTP (4 days vs. 2 days, P =
      0.014). All HHV6-positive patients and most (80%) of the HHV6-negative patients
      received systemic corticosteroids. Among the HHV6-negative patients, those who
      received corticosteroids showed significantly shorter CTP than those who did not
      (3 days vs. 2 days, P = 0.043). Additionally, there was a trend towards shorter
      hospital LOS and Tfeb among HHV6-negative patients who received corticosteroids
      vs. those who did not, although these differences were not statistically
      significant. The most common inciting drugs included trimethoprim
      sulfamethoxazole (34%), phenytoin (10%) and amoxicillin (10%). CONCLUSIONS: Human
      herpesvirus6 positivity with DHS is associated with a more severe disease course.
      Treatment with systemic corticosteroids was associated with a trend towards
      reduced hospital LOS and Tfeb, and a significantly reduced number of days until
      cessation of progression.

PMID- 25369240
TI  - Novel nanofiltration membranes consisting of a sulfonated pentablock copolymer
      rejection layer for heavy metal removal.
AB  - Facing stringent regulations on wastewater discharge containing heavy metal ions,
      various industries are demanding more efficient and effective treatment methods.
      Among the methods available, nanofiltration (NF) is a feasible and promising
      option. However, the development of new membrane materials is constantly required
      for the advancement of this technology. This is a report of the first attempt to
      develop a composite NF membrane comprising a molecularly designed pentablock
      copolymer selective layer for the removal of heavy metal ions. The resultant NF
      membrane has a mean effective pore diameter of 0.50 nm, a molecular weight cutoff
      of 255 Da, and a reasonably high pure water permeability (A) of 2.4 LMH/bar. The
      newly developed NF membrane can effectively remove heavy metal cations such as
      Pb(2+), Cd(2+), Zn(2+), and Ni(2+) with a rejection of >98.0%. On the other hand,
      the membrane also shows reasonably high rejections toward anions such as HAsO4(2
      ) (99.9%) and HCrO4(-) (92.3%). This performance can be attributed to (1) the
      pentablock copolymer's unique ability to form a continuous water transport
      passageway with a defined pore size and (2) the incorporation of polyethylenimine
      as a gutter layer between the selective layer and the substrate. To the best of
      our knowledge, this is the first reported NF membrane comprising this pentablock
      copolymer as the selective material. The promising preliminary results achieved
      in this study provide a useful platform for the development of new NF membranes
      for heavy metal removal. 

PMID- 25369241
TI  - Water-soluble polyelectrolyte complexes of Astramol poly(propyleneimine)
      dendrimers with poly(methacrylate) anion.
AB  - Water-soluble complexes formed by pyrenyl-tagged poly(methacrylate) anion with
      cationic DAB-dendr-(NH2)x of five generations, x = 4, 8, 16, 32, and 64 were
      prepared and studied. The ability of the dendrimers to quench the pyrenyl
      fluorescence was used to monitor formation/dissociation of the complexes by
      fluorescence quenching technique. In salt-free solutions, dissociation of the
      complexes occurred in highly acidic and highly alkaline media independently on
      the dendrimer generation, whereas stability of the complexes against destruction
      by added salt (NaCl) enhanced markedly with x increase. Phase separations were
      dependent on pH and charged ratio of the components, but independent of a
      dendrimer generation. By contrast, in water-salt solutions the generation had a
      profound impact on phase diagram manifested by a considerable extension of a
      heterogeneity region as x increased. These findings strongly suggest that the
      complexes obey the main regularities ascertained for polyelectrolyte complexes of
      oppositely charged polyions. The revealed possibility of preparing negatively
      charged and positively charged complexes with controllable stability and
      solubility demonstrates potentialities of Astramol dendrimers for design self
      assembled and self-adjusted systems attractive for biotechnological and
      biomedical applications. 

PMID- 25369239
TI  - Inhibition of kidney proximal tubular glucose reabsorption does not prevent
      against diabetic nephropathy in type 1 diabetic eNOS knockout mice.
AB  - BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) is the main
      luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria
      and improved glycaemic control. Drugs inhibiting this transporter have recently
      been approved for clinical use and have been suggested to have potential
      renoprotective benefits by limiting glycotoxicity in the proximal tubule. We
      aimed to determine the renoprotective benefits of empagliflozin, an SGLT2
      inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND
      METHODS: We induced diabetes using a low dose streptozotocin protocol in 7-8 week
      old endothelial nitric oxide (eNOS) synthase knockout mice. We measured fasting
      blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio.
      Renal histology was assessed for inflammatory and fibrotic changes. Renal
      cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose
      transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes
      were compared to diabetic animals receiving the angiotensin receptor blocker
      telmisartan (current best practice). RESULTS: Diabetic mice had high matched
      blood glucose levels. Empagliflozin did not attenuate diabetes-induced
      albuminuria, unlike telmisartan. Empagliflozin did not improve
      glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis,
      while telmisartan attenuated these. Empagliflozin did not modify tubular toll
      like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the
      upregulation of macrophage chemoattractant protein-1 (MCP-1), transforming growth
      factor beta1 and fibronectin mRNA observed in the diabetic animals, while
      telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin
      increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression
      in comparison to untreated diabetic mice. However no significant difference was
      found in protein expression of GLUT1 or SGLT2 among the different groups.
      CONCLUSION: Hence SGLT2 inhibition does not have renoprotective benefits
      independent of glucose lowering.

PMID- 25369242
TI  - Melatonin feedback on clock genes: a theory involving the proteasome.
AB  - The expression of 'clock' genes occurs in all tissues, but especially in the
      suprachiasmatic nuclei (SCN) of the hypothalamus, groups of neurons in the brain
      that regulate circadian rhythms. Melatonin is secreted by the pineal gland in a
      circadian manner as influenced by the SCN. There is also considerable evidence
      that melatonin, in turn, acts on the SCN directly influencing the circadian
      'clock' mechanisms. The most direct route by which melatonin could reach the SCN
      would be via the cerebrospinal fluid of the third ventricle. Melatonin could also
      reach the pars tuberalis (PT) of the pituitary, another melatonin-sensitive
      tissue, via this route. The major 'clock' genes include the period genes, Per1
      and Per2, the cryptochrome genes, Cry1 and Cry2, the clock (circadian locomotor
      output cycles kaput) gene, and the Bmal1 (aryl hydrocarbon receptor nuclear
      translocator-like) gene. Clock and Bmal1 heterodimers act on E-box components of
      the promoters of the Per and Cry genes to stimulate transcription. A negative
      feedback loop between the cryptochrome proteins and the nucleus allows the Cry
      and Per proteins to regulate their own transcription. A cycle of ubiquitination
      and deubiquitination controls the levels of CRY protein degraded by the
      proteasome and, hence, the amount of protein available for feedback. Thus, it
      provides a post-translational component to the circadian clock mechanism. BMAL1
      also stimulates transcription of REV-ERBalpha and, in turn, is also partially
      regulated by negative feedback by REV-ERBalpha. In the 'black widow' model of
      transcription, proteasomes destroy transcription factors that are needed only for
      a particular period of time. In the model proposed herein, the interaction of
      melatonin and the proteasome is required to adjust the SCN clock to changes in
      the environmental photoperiod. In particular, we predict that melatonin
      inhibition of the proteasome interferes with negative feedback loops (CRY/PER and
      REV-ERBalpha) on Bmal1 transcription genes in both the SCN and PT. Melatonin
      inhibition of the proteasome would also tend to stabilize BMAL1 protein itself in
      the SCN, particularly at night when melatonin is naturally elevated. Melatonin
      inhibition of the proteasome could account for the effects of melatonin on
      circadian rhythms associated with molecular timing genes. The interaction of
      melatonin with the proteasome in the hypothalamus also provides a model for
      explaining the dramatic 'time of day' effect of melatonin injections on
      reproductive status of seasonal breeders. Finally, the model predicts that a
      proteasome inhibitor such as bortezomib would modify circadian rhythms in a
      manner similar to melatonin. 

PMID- 25369243
TI  - Atomoxetine in autism spectrum disorder: no effects on social functioning; some
      beneficial effects on stereotyped behaviors, inappropriate speech, and fear of
      change.
AB  - Abstract Objective: The objective of this study was to investigate the short-term
      treatment effects of atomoxetine on autism spectrum disorder (ASD) symptoms in
      children and adolescents with both ASD and attention-deficit/hyperactivity
      disorder (ADHD). METHODS: A total of 97 patients 6-17 years of age, with ASD and
      ADHD, were treated with 1.2 mg/kg/day of atomoxetine during an 8 week double
      blind placebo-controlled period. Here, we investigated effects on two parent
      based secondary outcome measures, the Aberrant Behavior Checklist (ABC) and the
      Children's Social Behavior Questionnaire (CSBQ). RESULTS: After 8 weeks of double
      blind treatment, atomoxetine administration was associated with significant
      treatment effects on the ABC subscales Hyperactivity, Inappropriate Speech, and
      Stereotypic Behavior, and on the CSBQ subscale Fear for Changes. CONCLUSIONS: Our
      study results indicate no beneficial effects of atomoxetine on social
      functioning. However, atomoxetine may ameliorate restricted and stereotyped
      behaviors and communication. This study has been registered in ClinicalTrials.gov
      ( www.clinicaltrials.gov ) under registration number NCT00380692.

PMID- 25369244
TI  - Skeletal muscle toxicity in HIV-1-infected patients treated with a raltegravir
      containing antiretroviral therapy: a cohort study.
AB  - To evaluate the frequency of myopathy and serum creatine kinase (CK) elevation
      associated with the use of the integrase inhibitor raltegravir we conducted a
      retrospective, cohort analysis assessing the incidence of skeletal muscle
      toxicity among HIV-infected patients treated with raltegravir. Adult HIV-infected
      patients who started a raltegravir-containing therapy were enrolled into the
      study. The skeletal muscle toxicity was defined by the presence of one or more of
      the following parameters: (1) isolated and significant CK elevation without signs
      or symptoms; (2) diffuse myalgia without weakness; (3) proximal muscle weakness;
      (4) rhabdomyolysis. On the whole, 155 patients were included in the study, with a
      mean age of 49.2 years; the median duration of the raltegravir treatment was 30.7
      months. The overall frequency of skeletal muscle toxicity was 23.9%, with an
      incidence of 4.7/100 person-years. An isolated CK elevation was reported in 21.3%
      of cases, while less than 3% of patients complained of myalgia or muscle
      weakness. The CK elevation was usually of grade 1 or 2 and self-limiting, and
      laboratory or clinical abnormalities did not require discontinuation of
      raltegravir in any patient. Factors significantly associated with skeletal muscle
      toxicity were previous use of zidovudine, higher baseline CK levels, previous
      increase of the CK levels, and a higher body mass index. Skeletal muscle toxicity
      is not an unusual adverse event in subjects receiving raltegravir, but it is
      usually represented by a mild-to-moderate increase in CK concentration, while
      clinical symptoms of myopathy are very uncommon.

PMID- 25369245
TI  - DBT- and DBTO2-induced dysplasia and their associated proteomic alterations in
      the small intestines of Wistar rats.
AB  - Dibenzothiophene (DBT) and its oxidized derivative dibenzothiophene sulfone
      (DBTO2) are important representatives of polycyclic aromatic hydrocarbons (PAHs).
      Due to the importance of PAHs in oncogenesis and the lack of toxicological
      investigations related to DBT and DBTO2, this work proposes to assess their toxic
      and molecular effects caused by chronic treatment of Wistar rats. In parallel,
      their effects were compared to those caused by treatment with 1,2
      dimethylhydrazine (DMH), a classic mutagenic agent. At the 14th day post
      treatment, the animals were sacrificed and blood withdrawn for hematology and
      evaluation of liver and pancreatic functions. No significant alterations were
      observed. Nevertheless, histopathological analyses revealed dysplastic lesions in
      the intestines of animals treated with DBT and DBTO2. CD44 and carcinoembryonic
      antigen (CEA) staining demonstrated an approximately 3-fold increase in
      expression of both tissue markers for animals administered DBT, DBTO2, and DMH. A
      comparative two-dimensional gel analysis revealed additional 23 proteins
      exhibiting altered levels in the small intestines caused by exposure to DBT and
      DBTO2. At last, a protein-metabolite interaction map provided major insights into
      the metabolism of the dysplastic tissues. Our results provided strong evidence
      that DBT and its derivative could potentially act as cancer inducers,
      highlighting their toxicological and environmental relevance. 

PMID- 25369246
TI  - Early sodium dodecyl sulfate induced collapse of alpha-synuclein correlates with
      its amyloid formation.
AB  - The aggregation of alpha-synuclein (A-syn) has been implicated strongly in
      Parkinson's disease (PD). In vitro studies established A-syn to be a member of
      the intrinsically disordered protein (IDP) family. This protein undergoes
      structural interconversion between an extended and a compact state, and this
      equilibrium influences the mechanism of its aggregation. A combination of
      fluorescence resonance energy transfer (FRET) and fluorescence correlation
      spectroscopy (FCS) has been used to study the membrane induced conformational
      reorganization and aggregation of A-syn. Different structural and conformational
      events, including the early collapse, the formation of the secondary structure,
      and aggregation have been identified and characterized using FCS and other
      biophysical methods. In addition, the concentrations of glycerol and urea have
      been varied to study the effect of solution conditions on the above
      conformational events. Further, we have extended this study on a number of A-syn
      mutants, namely, A30P, A53T, and E46K. These mutants are chosen because of their
      known implications in the disease pathology. The variation of solution conditions
      and mutational analyses suggest a strong correlation between the extent of early
      collapse and the onset of aggregation in PD. 

PMID- 25369247
TI  - Effect of inorganic salts on the volatility of organic acids.
AB  - Particulate phase reactions between organic and inorganic compounds may
      significantly alter aerosol chemical properties, for example, by suppressing
      particle volatility. Here, chemical processing upon drying of aerosols comprised
      of organic (acetic, oxalic, succinic, or citric) acid/monovalent inorganic salt
      mixtures was assessed by measuring the evaporation of the organic acid molecules
      from the mixture using a novel approach combining a chemical ionization mass
      spectrometer coupled with a heated flow tube inlet (TPD-CIMS) with kinetic model
      calculations. For reference, the volatility, i.e. saturation vapor pressure and
      vaporization enthalpy, of the pure succinic and oxalic acids was also determined
      and found to be in agreement with previous literature. Comparison between the
      kinetic model and experimental data suggests significant particle phase
      processing forming low-volatility material such as organic salts. The results
      were similar for both ammonium sulfate and sodium chloride mixtures, and
      relatively more processing was observed with low initial aerosol organic molar
      fractions. The magnitude of low-volatility organic material formation at an
      atmospherically relevant pH range indicates that the observed phenomenon is not
      only significant in laboratory conditions but is also of direct atmospheric
      relevance. 

PMID- 25369248
TI  - [Clinical pathology of recurrent hepatitis B after liver transplantation].
AB  - OBJECTIVE: To investigate the clinical pathology of recurrent hepatitis B after
      orthotopic liver transplantation (OLT). METHODS: The clinical manifestation and
      hepatic pathological characteristics of 12 patients with recurrent hepatitis B
      after OLT were examined in this study by using hematoxylin and eosin
      staining,immunochemical staining of hepatitis B surface antigen and hepatitis B
      core antigen,tissue in situ hybridization of hepatitis B virus (HBV) DNA, and
      Mallory's trichrome staining.The survival rate of these OLT patients was assessed
      by Kaplan-Meier analysis. RESULTS: The early stage of recurrent HBV infection in
      patients with OLT was characterized by active HBV replication and mild-to
      moderate inflammation in the liver. Three of the 12 patients who were treated
      with combination therapy group were carriers of YMDD mutants and all three showed
      improvement in liver function and hepatic histology after receiving adefovir
      dipivoxil,instead of lamivudine,in the early stage of recurrent hepatitis B after
      OLT. Among the patients treated with lamivudine monotherapy, four did not achieve
      improvement at the early stage of recurrent hepatitis B and developed fibrosing
      cholestatic hepatitis (FCH). CONCLUSION: Recurrent hepatitis B in patients who
      underwent OLT was characterized by mild-to-moderate viral hepatitis at the early
      stage and FCH at the later stage. Effective antiviral intervention at the early
      stage may reverse recurrent hepatitis B and prevent the disease progression to
      fatal FCH.

PMID- 25369249
TI  - [Alteration of the glycan profile of serum glycoproteins during the
      seroconversion process in hepatitis B virus-infected patients treated with
      antiviral therapy and its clinical significance].
AB  - OBJECTIVE: To use a lectin microarray to study the alteration of glycan affinity
      profiles of serum glycoproteins during the hepatitis B e antigen (HBeAg) and
      hepatitis B surface antigen (HBsAg) seroconversion in patients with chronic
      hepatitis B (CHB) following treatment with antiviral therapy,and to explore its
      biological significance. METHODS: CHB patients were divided into the following
      four groups:untreated HBeAg-positive,HBeAg seroconversion after anti-HBV
      therapy,HBsAg loss after anti-HBV therapy,and healthy individuals
      (controls).Serum samples were collected from each participant,depleted of high
      abundance proteins and analyzed by a lectin microarray containing 50 lectins.The
      lectin-affinity glycan profiles of serum proteins were partially verified by
      lectin blotting.Between-group differences were analyzed by one-way analysis of
      variance,and pairwise comparisons were carried out with the Student-Newman-Keuls
      (SNK) method. RESULTS: The results from the lectin microarray and lectin blotting
      assay showed significantly reduced affinity for 16 lectins in the untreated HBeAg
      positive group compared to the control group (P less than 0.05);in addition,the
      specific glycan profiles of the untreated HBeAg-positive group included decreased
      terminal and core fructose,GalNAc alpha-Thr/Ser (T,Tn-antigen),GalNac
      alpha,terminal beta1-4,and beta-D galactose,bisecting and/or GlcNAc,mannose and
      Sia.However,the HBeAg seroconversion after anti-HBV therapy group showed enhanced
      binding of PSA,MPL and the above-mentioned 16 lectins (P less than
      0.05),suggesting that the reduced serum glycoprotein glycan structures returned
      to normal or slightly higher than healthy levels after the therapy-induced
      seroconversion.Comparison of the group with HBsAg loss after anti-HBV therapy to
      the group with HBeAg seroconversion after anti-HBV therapy showed the binding
      ability of ten lectins (AAL,ACL,HAL,HPL,RCA-I,LEL,STL,PHA-E,NML and PCL) were
      weakened to near control levels and six lectins (VAL,LCA,GNL,PSA,MPL and JAC)
      were significantly strengthened (all P less than 0.05). These findings implied
      that the glycan containing terminal fructose, GalNacalpha, terminal beta1-4
      galactose,and bisecting GlcNAc glycan structures dropped to near control levels,
      while the terminal beta-D-galactose residues and core fructose structure
      increased significantly. CONCLUSION: The glycan structures of serum glycoproteins
      are closely related to HBeAg and HBsAg seroconversion in CHB patients.It is
      possible that a special lectin binding glycan involving the terminal beta-D
      galactose residues and core fructose may act as sugar markers associated with the
      disappearance of serum HBsAg during anti-HBV therapy for CHB.

PMID- 25369250
TI  - [Autologous peripheral blood CD34+ stem cells transplanted into 100 patients with
      advanced cirrhosis].
AB  - OBJECTIVE: To investigate whether transplantation of autologous peripheral blood
      CD34+ stem cells is a viable approach for treating patients with advanced
      cirrhosis,which is currently hindered by a shortage in liver donors. METHODS: A
      total of 100 patients with advanced cirrhosis and who had failed to respond to
      conservative therapy were recruited for transplantation of autologous peripheral
      blood CD34+ stem cells.The success of transplantation was investigated 6-and 12
      months later by measuring markers of liver biosynthesis function
      (coagulation,albumin level,indocyanine green clearance,Child-Pugh score) and
      assessing pathological changes (Knodell score) and morphologic changes in the
      liver tissue.Complications were also recorded during follow-up. RESULTS: The 1
      year cumulative survival rate was 100%. Fifty-two patients with massive ascites
      showed gradual reduction and disappearance of the ascites.Four patients
      experienced upper gastrointestinal bleeding and three patients developed with
      hepatic encephalopathy (I-II degree) at 3 months post-transplantation.All
      patients showed significantly improved liver biosynthesis function,liver
      elasticity and Knodell score after transplantation (P less than 0.05).
      CONCLUSION: Autologous peripheral blood CD34+ stem cell transplantation is a safe
      and effective treatment for advanced cirrhosis,and has high cost-benefit since it
      improves liver function,liver histology,and quality of life.

PMID- 25369251
TI  - [Changes in mitochondria fusion protein-2 hepatic expression in conditions of
      liver cirrhosis and acute on chronic liver failure].
AB  - OBJECTIVE: To determine the differential protein and mRNA expressions of
      mitochondria fusion protein-2 (Mfn2) in hepatic tissues in conditions of
      cirrhosis and acute on chronic liver failure using rat model systems,and to
      determine the correlative effects on production of adenosine triphosphate (ATP)
      and reactive oxygen species (ROS). METHODS: A liver cirrhotic rat model (LC rats)
      was established by intraperitoneal injection of carbon tetrachloride (CCl4,in
      vegetable oil),and these mice were subsequently used (10 weeks later) to
      establish the acute on chronic liver failure rat model (LF rats) by injecting
      lipopolysaccharide and D-amino-galactose.Control groups (normal controls,NC rats)
      were established for each model by intraperitoneal injection of vegetable oil
      only.Protein expression of Mfn2 in liver was quantified by western blotting with
      fluorescence densitometry and immunofluorescence staining,and mRNA expression was
      measured by real-time fluorescence quantitative PCR.ROS levels in liver were
      measured by fluorescence spectrophotometry,and ATP content was measured by
      bioluminescence assay.Significance of inter-group differences was assessed by one
      way ANOVA,and correlations were determined using bivariate statistical modeling.
      RESULTS: Mfn2 protein expression was significantly lower in the liver tissues
      from modeled rats than that from the control rats (LC:0.051+/-0.004 and
      LF:0.037+/-0.007 vs.NC:0.254+/-0.008;F=444.98,P less than 0.05).The mRNA
      expression followed the same trend of lower expression (LC:21.21+/-0.93 and
      LF:24.35+/-0.85 vs.NC:19.09+/-0.69; F=66.941,P less than 0.05).The ATP content in
      liver tissues was also significantly lower in the modeled rats (LC:2.07+/-0.05
      mol/L and LF:1.81+/-0.11 mol/L vs.NC:3.24+/-0.08 mol/L; F =574.21,P less than
      0.05).Lower Mfn2 expression was correlated with lower ATP content (r =0.982) and
      higher ROS content (r =0.803). CONCLUSION: Reduced Mfn2 expression in liver
      tissue may cause a decrease in ATP synthesis and increase in ROS
      generation,thereby disrupting metabolism and increasing oxidative stress in the
      liver under conditions of cirrhosis and liver failure.

PMID- 25369252
TI  - [Relationship between hepatocellular carcinoma and the interaction between hMSH2
      polymorphisms and environmental factors].
AB  - OBJECTIVE: To use a hospital-based case-control study design to investigate the
      relationship between hepatocellular carcinoma (HCC) and the interaction of
      polymorphisms in the human mismatch repair gene,hMSH2,with environmental factors.
      METHODS: Cases of new-onset,histopathology-diagnosed,and untreated (no
      chemotherapy or radiation therapy) HCC were enrolled between September 2009 and
      September 2012.A non-HCC healthy control group was also enrolled and was composed
      of individuals living in the same region as the cases for more than 10 years and
      age-/sex-matched with similar socioeconomic characteristics.All enrollees
      underwent hMSH2 genotyping by real-time PCR.T-test,chi-square test and
      unconditional logistic regression analysis was used to analyze the difference in
      allele frequencies among the case and control groups and the relationship between
      hMSH2 polymorphisms and environmental factors. RESULTS: Frequencies of hMSH2
      rs2303428 CC,CT and TT genotypes in the HCC group were significantly different
      than in the control group (14.13% vs.8.21%,47.02% vs.49.47%,and 38.85%
      vs.42.32%;x 2=8.289,P =0.016).Individuals carrying the hMSH2 rs2303428 T allelic
      gene had a significantly increased risk compared to those with the hMSH2
      rs2303428 C allelic gene (adjusted OR=1.228).Interactions were found between the
      hMSH2 genotype and hepatitis B surface antigen (HBsAg)-positive hepatitis
      infection (adjusted OR=1.865) and history of cancer (adjusted OR=5.634).There was
      no relation between hMSH2 gene rs4952887 and rs2059520 and liver cancer
      development or interaction with environmental factors. CONCLUSION: The hMSH2
      rs2303428 genotype is positively related to risk of HCC in Chinese,with HBsAg
      positive hepatitis infection starus and history of cancer increasing the risk.

PMID- 25369253
TI  - [Correlation analysis of magnetic resonance imaging characteristics and
      intrahepatic recurrence of small hepatocellular carcinoma after radiofrequency
      ablation].
AB  - OBJECTIVE: To investigate the correlation between magnetic resonance imaging
      (MRI) characteristics and intrahepatic recurrence of small hepatocellular
      carcinoma (HCC) after radiofrequency ablation (RFA). METHODS: A total of 34
      patients with 39 small HCC who underwent RFA were included in our study.MRI
      characteristics were compared between the recurrence group and the non-recurrence
      group; and a subgroup comparison was also made between the solitary recurrence
      group and the multiple recurrence group.Kaplan-Meier test,t-test/Mann-Whitney U
      test,Fisher's exact test and F-test were used for statistical analyses. RESULTS:
      The median follow-up period was 25 (4-45) months and recurrence was observed in
      19 (55.9%) of the patients.The 12-and 24-month cumulative recurrence-free
      survival rates were 71.3% and 51.8%,respectively.The recurrence group had a
      higher prevalence of lack of tumour capsule before RFA (P =0.017),no or disrupted
      periablational enhancement within 24 hours after RFA (P =0.012),and a smaller
      ablative margin (P=0.037).Meanwhile,the average apparent diffusion coefficient
      value within 24 hours after RFA was higher in the multiple recurrence group (1.57
      * 10-3mm2/s) than in the solitary recurrence group (1.34 * 10(-3) mm2/s) (P
      =0.04). CONCLUSION: MRI can provide early noninvasive findings useful for
      advanced warning ofintrahepatic recurrence after RFA.

PMID- 25369254
TI  - [Cryopreservation of microencapsulated human hepatocytes].
AB  - OBJECTIVE: To establish a stable method of isolation, culture and
      cryopreservation of adult primary hepatocytes to provide potential hepatocyte
      resources for therapeutic usage in hepatocyte transplantation and bioartificial
      liver support systems for the treatment of acute and chronic liver diseases,and
      for experimental usage as an in vitro model of the liver. METHODS: Adult
      hepatocytes from 20 human donors undergoing partial hepatectomy were isolated
      using a two-step extracoporeal collagenase perfusion technique.Seven
      preincubation time points (2h,6h,12h,24h,36h,48h and 72h) were selected for
      optimization.After pre-incubation at 4 degrees C for 12-24h in HepatoZYME-SFM
      (the optimal condition),hepatocytes were microencapsulated using alginate-poly-L
      lysine-alginate microcapsules,transferred to a complete medium containing 10%
      dimethyl sulphoxide and immediately placed into an isopropanol progressive
      freezing container for overnight freezing at -80 degrees C followed by immersion
      in liquid nitrogen the next day.During the post-thawing culture period,the cells
      were tested for albumin secretion,urea synthesis,cell cycling,transcription and
      protein synthesis (measuring mRNA and protein levels),and the morphological
      structure and pathology,for comparison with the features from before
      microencapsulated cryopreservation (PMC). RESULTS: The viability and plating
      efficiency of the hepatocytes isolated using the two-step extracorporeal
      collagenase perfusion technique were 75.0+/-4.6% and 72.0+/-6.0%,respectively.The
      pre-incubation times of 12h and 24h (viability:61.4+/-4.8% and 62.0+/-5.6%;
      plating efficiency:3.2+/-5.8% and 62.6+/-3.6%,respectively) showed significantly
      higher albumin secretion than all other time points tested (F =40.3,all P less
      than 0.05).Compared with the immediate cryopreservation (immediately frozen
      control) hepatocytes,the PMC hepatocytes showed significantly better
      transcription and protein synthesis and higher albumin secretion and urea
      levels.The PMC group did not show a significantly different level of albumin
      production from the directly cultured hepatocytes (culture day 2:ll9.2ng/ml
      vs.131.36ng/ml,P =0.051; day 3:110ng/ml vs.120.4ng/ml,P=0.063; day 4:98.2ng/ml
      vs.109.8ng/ml,P more than 0.05).However,over culturing days 2,3 and 4,comparison
      of the PMC hepatocytes to the immediate cryopreservation hepatoeytes showed the
      former to have significantly higher secretion of albumin (119.2ng/ml
      vs.101.2ng/ml,110.0ng/ml vs.87.6ng/ml and 98.2ng/ml vs.73.8ng/ml; all P less than
      0.05) and urea level (7.83 mug/ml vs.6.79 mug/ml,6.83 mug/ml vs.5.89 mug/ml and
      5.85 mug/ml vs.4.83 mug/ml; all P less than 0.05).The post-thawed PMC hepatoeytes
      showed preservation of the morphological structure,while the immediate
      cryopreservation hepatocytes did not. CONCLUSION: The two-step extracorporeal
      collagenase perfusion technique after partial hepatectomy is a novel,simple,and
      reliable method for hepatocyte isolation.Pre-incubation at 4 degrees C for 12-24h
      before the microencapsulation cryopreservation allows for efficient recovery of
      functional and morphological integrity after thawing and provides viable
      hepatoeytes that may be useful for clinical applications in
      pharmacotoxicology,bioartificial liver therapy and cell therapy in humans.

PMID- 25369255
TI  - [Correlation analysis of survival period and CD4+ Tcell-iATP levels in liver
      transplant recipients].
AB  - OBJECTIVE: To analyze the correlation between survival time after liver
      transplantation and the intracellular (i)ATP levels of CD4+ T cells. METHODS:
      Liver transplantation patients treated in our hospital,and with complete follow
      up data,were enrolled retrospectively in our study (between July 2010 to October
      2012) and divided into six groups according to survival time: less than 1 year,1
      2 years,2-3 years,3-4 years,4-8 years,and more than 8 years.The less than 1 year
      survival group was further sub-divided for survival less than 1 month,1-2
      months,2-3 months,3-5 months and 5-12 months.Blood samples collected from all
      enrollees (n=273) were analyzed by the Cylex ImmuKnow Cell Function Assay to
      detect the iATP level in CD4+ T cells.Correlation of iATP level in CD4+ T cells
      with survival time was statistically analyzed. RESULTS: The levels of CD4+ T cell
      iATP were significantly different among the various survival recipient groups by
      years: less than 1 year:325+228 ng/ml,1-2 years:216-147 ng/ml,2-3 years:225-172
      ng/ml,3-5 years:236-184 ng/ml,4-8 years:298-145 ng/ml,more than 8 years:323-153
      ng/ml.In addition,the levels of CD4+ T cell-iATP were significantly different
      between the groups of patients who survived less than 1 year: less than 1
      month:441+255 ng/ml,1-2 months:357-235 ng/ml,2-3 months:353-257 ng/ml,3-5
      months:202-123 ng/ml,5-12 months:234-145 ng/ml. CONCLUSION: There is a
      relationship between levels of iATP in CD4+ T cells and survival time after liver
      transplantation.For patients with postoperative survival time of less than 1
      year,the CD4+ T cell iATP level will not accurately reflect the status of CD4+ T
      cells' immune activation.For patients with postoperative survival time of 2-4
      years,the CD4+ T cell-iATP level is relatively low and the CD4+ T lymphocyte
      activation status is in the low reaction zone.Patients with postoperative
      survival time of more than 5 years had higher CD4+ T cell-iATP level then 2-4
      years survivors,and had stable CD4+ T cell immune activation.

PMID- 25369256
TI  - High intraocular pressure following anti-vascular endothelial growth factor
      therapy: proposed pathophysiology due to altered nitric oxide metabolism.
AB  - The nitric oxide (NO) pathway and its physiological significance on relaxing
      smooth muscle and endothelial cells throughout the body is well outlined and
      understood. Components of this pathway have been located in the ocular anterior
      and posterior chambers, and they have been connected with vascular, retinal, and
      trabecular meshwork normal physiology. Nitric oxide has been shown to increase
      anterior chamber aqueous outflow via reduction in trabeculocyte size and smooth
      muscle contractility, and Schlemm's canal vasodilation. Anti-vascular endothelial
      growth factor (VEGF) therapy has been shown to disrupt the normal nitric oxide
      signaling pathway, producing systemic arterial hypertension following
      systemically administered anti-VEGF in oncology by exactly that mechanism.
      Intravitreal anti-VEGF therapy is now considered a standard of care in several
      retinal diseases. Sustained elevated intraocular pressure (IOP) has been
      described as a potential adverse effect of therapy that appears related to the
      number of injections, and it can be produced by any of the various anti-VEGF
      compounds. We propose a novel mechanism responsible for the increase in IOPs
      following prolonged intravitreal anti-VEGF therapy. This mechanism postulates a
      rise in IOP due to a decrease in aqueous outflow from relatively decreased levels
      of available nitric oxide in the anterior chamber because of anti-VEGF inhibition
      of nitric oxide synthase. This article outlines the novel mechanism, which
      provides a likely explanation for this consequence, along with offering
      therapeutic targets for future research and treatment.

PMID- 25369258
TI  - Identification of two p23 co-chaperone isoforms in Leishmania braziliensis
      exhibiting similar structures and Hsp90 interaction properties despite divergent
      stabilities.
AB  - The small acidic protein called p23 acts as a co-chaperone for heat-shock protein
      of 90 kDa (Hsp90) during its ATPase cycle. p23 proteins inhibit Hsp90 ATPase
      activity and show intrinsic chaperone activity. A search for p23 in protozoa,
      especially trypanosomatids, led us to identify two putative proteins in the
      Leishmania braziliensis genome that share approximately 30% identity with each
      other and with the human p23. To understand the presence of two p23 isoforms in
      trypanosomatids, we obtained the recombinant p23 proteins of L. braziliensis
      (named Lbp23A and Lbp23B) and performed structural and functional studies. The
      recombinant proteins share similar solution structures; however, temperature- and
      chemical-induced unfolding experiments showed that Lbp23A is more stable than
      Lbp23B, suggesting that they may have different functions. Lbp23B prevented the
      temperature-induced aggregation of malic dehydrogenase more efficiently than did
      Lbp23A, whereas the two proteins had equivalent efficiencies with respect to
      preventing the temperature-induced aggregation of luciferase. Both proteins
      interacted with L. braziliensis Hsp90 (LbHsp90) and inhibited its ATPase
      activity, although their efficiencies differed. In vivo identification studies
      suggested that both proteins are present in L. braziliensis cells grown under
      different conditions, although Lbp23B may undergo post-translation modifications.
      Interaction studies indicated that both Lbp23 proteins interact with LbHsp90.
      Taken together, our data suggest that the two protozoa p23 isoforms act similarly
      when regulating Hsp90 function. However, they also have some differences,
      indicating that the L. braziliensis Hsp90 machine has features providing an
      opportunity for novel forms of selective inhibition of protozoan Hsp90.

PMID- 25369257
TI  - Early-life exposure to organophosphate pesticides and pediatric respiratory
      symptoms in the CHAMACOS cohort.
AB  - BACKGROUND: Although pesticide use is widespread, the possible effect of early
      life exposure to organophosphate (OP) on pediatric respiratory health is not well
      described. OBJECTIVES: We investigated the relationship between early-life
      exposure to OPs and respiratory outcomes. METHODS: Participants included 359
      mothers and children from the CHAMACOS birth cohort. Dialkyl phosphate (DAP)
      metabolites of OP pesticides, specifically diethyl (DE) and dimethyl (DM)
      phosphate metabolites, were measured in urine from mothers twice during pregnancy
      (mean = 13 and 26 weeks gestation) and from children five times during childhood
      (0.5-5 years). Childhood DAP concentrations were estimated by the area under
      curve (AUC). Mothers reported their child's respiratory symptoms at 5 and 7 years
      of age. We used generalized estimating equations (GEE) to examine associations of
      prenatal and childhood DAP concentrations with repeated measures of respiratory
      symptoms and exercise-induced coughing at 5 and 7 years of age, adjusting for
      child's sex and age, maternal smoking during pregnancy, secondhand tobacco smoke,
      season of birth, PM2.5, breastfeeding, mold and cockroaches in home, and distance
      from highway. RESULTS: Higher prenatal DAP concentrations, particularly DE, were
      nonsignificantly associated with respiratory symptoms in the previous 12 months
      at 5 or 7 years of age [adjusted odds ratio (aOR) per 10-fold increase = 1.44;
      95% CI: 0.98, 2.12]. This association was strongest with total DAP and DE from
      the second half of pregnancy (aOR per 10-fold increase = 1.77; 95% CI: 1.06,
      2.95; and 1.61; 95% CI: 1.08, 2.39, respectively). Childhood DAP, DE, and DM
      concentrations were associated with respiratory symptoms and exercise-induced
      coughing in the previous 12 months at 5 or 7 years of age (total DAPs: aOR per 10
      fold increase = 2.53; 95% CI: 1.32, 4.86; and aOR = 5.40; 95% CI: 2.10, 13.91,
      respectively). CONCLUSIONS: Early-life exposure to OP pesticides was associated
      with respiratory symptoms consistent with possible asthma in childhood.

PMID- 25369259
TI  - The effect of enterohemorrhagic E. coli infection on the cell mechanics of host
      cells.
AB  - Enterohaemorrhagic E. coli (EHEC) is a type of human pathogenic bacteria. The
      main virulence characteristics of EHEC include the formation of attaching and
      effacing lesions (A/E lesions) and the production of one or more Shiga-like
      toxins, which may induce human uremic complications. When EHEC infects host
      cells, it releases translocated intimin receptor (Tir) and effector proteins
      inside the host cells, inducing the rearrangement and accumulation of the F-actin
      cytoskeleton, a phenotype leading to the formation of pedestals in the apical
      cell surface, and the growth of stress fibers at the base of the cells. To
      examine the effect of EHEC infection on cell mechanics, we carried out a series
      of experiments to examine HeLa cells with and without EHEC infection to quantify
      the changes in (1) focal adhesion area, visualized by anti-vinculin staining; (2)
      the distribution and orientation of stress fibers; and (3) the intracellular
      viscoelasticity, via directional video particle tracking microrheology. Our
      results indicated that in EHEC-infected HeLa cells, the focal adhesion area
      increased and the actin stress fibers became thicker and more aligned. The
      cytoskeletal reorganization induced by EHEC infection mediated a dramatic
      increase in the cytoplasmic elastic shear modulus of the infected cells, and a
      transition in the viscoelastic behavior of the cells from viscous-like to elastic
      like. These changes in mechanobiological characteristics might modulate the
      attachments between EHEC and the host cell to withstand exfoliation, and between
      the host cell and the extracellular matrix, and might also alter epithelial
      integrity. 

PMID- 25369260
TI  - Interactions of anaerobic bacteria with dental stem cells: an in vitro study.
AB  - BACKGROUND: In patients with periodontitis, it is highly likely that local
      (progenitor) cells encounter pathogenic bacteria. The purpose of this in vitro
      study was to elucidate how human dental follicle stem cells (hDFSC) react towards
      a direct challenge with anaerobic periodontal pathogens under their natural
      oxygen-free atmosphere. HDFSC were compared to human bone marrow mesenchymal stem
      cells (hBMSC) and differentiated primary human gingival fibroblasts (hGiF), as
      well as permanent gingival carcinoma cells (Ca9-22). METHODOLOGY/PRINCIPAL
      FINDINGS: The different cell types were investigated in a co-culture system with
      Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F.
      nucleatum). The viability of the cells and pathogens under anaerobic conditions,
      as well as interactions in terms of adherence and internalization, were examined.
      Additionally, the release of pro-inflammatory interleukin-8 (IL-8) and anti
      inflammatory interleukin-10 (IL-10) was quantified via enzyme-linked
      immunosorbent assay. The bacteria adhered less efficiently to hDFSC compared to
      Ca9-22 (P. gingivalis: 0.18% adherence to hDFSC; 3.1% adherence to Ca9-22).
      Similar results were observed for host cell internalization (F. nucleatum: 0.002%
      internalization into hDFSC; 0.09% internalization into Ca9-22). Statistically
      significantly less IL-8 was secreted from hDFSC after stimulation with F.
      nucleatum and P. gingivalis in comparison with hGiF (F. nucleatum: 2080.0 pg/ml-
      hGiF; 19.7 pg/ml--hDFSC). The IL-10 response of the differentiated cells was
      found to be low in relation to their pro-inflammatory IL-8 response.
      CONCLUSIONS/SIGNIFICANCE: The results indicate that dental stem cells are less
      prone to interactions with pathogenic bacteria than differentiated cells in an
      anaerobic environment. Moreover, during bacterial challenge, the stem cell immune
      response seems to be more towards an anti-inflammatory reaction. For a potential
      future therapeutic use of hDFSC, these findings support the idea of a save
      application.

PMID- 25369261
TI  - Factors affecting unhappiness at school among Japanese adolescents: an
      epidemiological study.
AB  - BACKGROUND: Unhappiness at school is one of the main reasons for truancy among
      adolescents. In order to assess this problem more thoroughly in the context of
      Japanese adolescents, the present study examined the associations between
      feelings of unhappiness at school and lifestyle habits, school life realities,
      and mental health status. METHOD: This study was designed as a cross-sectional
      survey. A self-administered questionnaire was provided to students enrolled in
      randomly selected junior and senior high schools throughout Japan. We calculated
      the percentages of both junior and senior high school students who felt unhappy
      at school based on factors related to school life, lifestyle habits, and mental
      health status. Multiple logistic regression analyses were performed in order to
      examine the associations between those factors and students' feelings of
      unhappiness at school. RESULTS: A total of 98,867 valid responses were analysed,
      7.9% (Boys: 8.4%, Girls: 7.4%) of which came from students who responded that
      they felt unhappy at school. For both junior and senior high school students, the
      percentages of those who felt unhappy at school were significantly higher among
      those who had not yet decided on their future life course, who did not
      participate in extracurricular activities, did not eat breakfast every day, went
      to bed late, had used tobacco or alcohol in the previous 30 days, and had poor
      mental health compared with others. The results of multiple logistic regression
      analyses indicated that the adjusted odds ratios for feeling unhappy at school
      with regard to the above-mentioned factors were significantly high for both
      junior and senior high school students. CONCLUSIONS: The present results suggest
      that school employees and administrators must provide health guidance to
      students, considering that irregular lifestyle habits, lower school engagement,
      smoking, drinking alcohol, and poor mental health status are all associated with
      maladaptation to school among adolescents.

PMID- 25369262
TI  - Efficient synthesis of ethisterone glycoconjugate via bis-triazole linkage.
AB  - Synthesis of sugar based triazolyl azido-alcohols was accomplished via one pot
      click reaction of glycosyl alkynes with epichlorohydrin in aqueous medium. All
      the developed triazolyl azido-alcohols were further utilized for the synthesis of
      bis-triazolyl ethisterone glycoconjugates using CuAAC reaction. The developed
      triazole-linked ethisterone glycoconjugates would be crucial in androgen receptor
      pharmacology and chemical biology. 

PMID- 25369263
TI  - Concise synthesis of the tetrasaccharide repeating unit of the O-polysaccharide
      isolated from Edwardsiella tarda PCM 1156 strain.
AB  - A convergent strategy has been developed for the synthesis of the tetrasaccharide
      repeating unit of the O-antigen from Edwardsiella tarda PCM 1156. Sequential
      glycosylations of a series of rationally protected monosaccharide intermediates
      were achieved either by the activation of thioglycosides using N-iodosuccinimide
      (NIS) in conjunction with H2SO4-silica or by activation of trichloroacetimidate
      by H2SO4-silica only. All glycosylation reactions resulted in the formation of
      the desired linkage with absolute stereoselectivity and yielded the required
      derivatives in good to excellent yields. Both azido and phthalimido groups have
      been used as the precursor of the desired acetamido group depending on the
      requirement of 1,2-cis- or 1,2-trans-glycosidic linkage. 

PMID- 25369264
TI  - BF3.Et2O- or DMAP-catalyzed double nucleophilic substitution reaction of
      aziridinofullerenes with sulfamides or amidines.
AB  - BF3.Et2O-catalyzed double nucleophilic substitution reaction of N
      tosylaziridinofullerene with sulfamides has been exploited for the easy
      preparation of cyclic sulfamide-fused fullerene derivatives. Moreover, the Lewis
      base catalyzed double amination of N-tosylaziridinofullerene, with amidines as
      the diamine source, is demonstrated for the first time. The present methods
      provide new routes to cyclic 1,2-diaminated [60]fullerenes. 

PMID- 25369265
TI  - Fibroblast growth factor 21 is not required for the reductions in circulating
      insulin-like growth factor-1 or global cell proliferation rates in response to
      moderate calorie restriction in adult mice.
AB  - Calorie restriction (CR) delays aging and extends lifespan in numerous organisms,
      including mice. Down-regulation of the somatotropic axis, including a reduction
      in insulin-like growth factor-1 (IGF-1), likely plays an important role in CR
      induced lifespan extension, possibly by reducing cell proliferation rates,
      thereby delaying replicative senescence and inhibiting tumor promotion.
      Accordingly, elucidating the mechanism(s) by which IGF-1 is reduced in response
      to CR holds therapeutic potential in the fight against age-related diseases. Up
      regulation of fibroblast growth factor 21 (FGF21) is one possible mechanism given
      that FGF21 expression is induced in response to nutritional deprivation and has
      been implicated as a negative regulator of IGF-1 expression. Here we investigated
      alterations in hepatic growth hormone (GH)-mediated IGF-1 production and
      signaling as well as the role of FGF21 in the regulation of IGF-1 levels and cell
      proliferation rates in response to moderate CR in adult mice. We found that in
      response to moderate CR, circulating GH and hepatic janus kinase 2 (JAK2)
      phosphorylation levels are unchanged but that hepatic signal transducer and
      activator of transcription 5 (STAT5) phosphorylation levels are reduced,
      identifying STAT5 phosphorylation as a potential key site of CR action within the
      somatotropic axis. Circadian measurements revealed that the relative level of
      FGF21 expression is both higher and lower in CR vs. ad libitum (AL)-fed mice,
      depending on the time of measurement. Employing FGF21-knockout mice, we
      determined that FGF21 is not required for the reduction in IGF-1 levels or cell
      proliferation rates in response to moderate CR. However, compared to AL-fed WT
      mice, AL-fed FGF21-knockout mice exhibited higher basal rates of cell
      proliferation, suggesting anti-mitotic effects of FGF21. This work provides
      insights into both GH-mediated IGF-1 production in the context of CR and the
      complex network that regulates FGF21 and IGF-1 expression and cell proliferation
      rates in response to nutritional status. 

PMID- 25369266
TI  - Biodegradation of microcystins during gravity-driven membrane (GDM)
      ultrafiltration.
AB  - Gravity-driven membrane (GDM) ultrafiltration systems require little maintenance:
      they operate without electricity at ultra-low pressure in dead-end mode and
      without control of the biofilm formation. These systems are already in use for
      water purification in some regions of the world where adequate treatment and
      distribution of drinking water is not readily available. However, many water
      bodies worldwide exhibit harmful blooms of cyanobacteria that severely lower the
      water quality due to the production of toxic microcystins (MCs). We studied the
      performance of a GDM system during an artificial Microcystis aeruginosa bloom in
      lake water and its simulated collapse (i.e., the massive release of microcystins)
      over a period of 21 days. Presence of live or destroyed cyanobacterial cells in
      the feed water decreased the permeate flux in the Microcystis treatments
      considerably. At the same time, the microbial biofilms on the filter membranes
      could successfully reduce the amount of microcystins in the filtrate below the
      critical threshold concentration of 1 ug L(-1) MC for human consumption in three
      out of four replicates after 15 days. We found pronounced differences in the
      composition of bacterial communities of the biofilms on the filter membranes.
      Bacterial genera that could be related to microcystin degradation substantially
      enriched in the biofilms amended with microcystin-containing cyanobacteria. In
      addition to bacteria previously characterized as microcystin degraders, members
      of other bacterial clades potentially involved in MC degradation could be
      identified.

PMID- 25369267
TI  - Accurate predictions of genetic circuit behavior from part characterization and
      modular composition.
AB  - A long-standing goal of synthetic biology is to rapidly engineer new regulatory
      circuits from simpler devices. As circuit complexity grows, it becomes
      increasingly important to guide design with quantitative models, but previous
      efforts have been hindered by lack of predictive accuracy. To address this, we
      developed Empirical Quantitative Incremental Prediction (EQuIP), a new method for
      accurate prediction of genetic regulatory network behavior from detailed
      characterizations of their components. In EQuIP, precisely calibrated time-series
      and dosage-response assays are used to construct hybrid phenotypic/mechanistic
      models of regulatory processes. This hybrid method ensures that model parameters
      match observable phenomena, using phenotypic formulation where current hypotheses
      about biological mechanisms do not agree closely with experimental observations.
      We demonstrate EQuIP's precision at predicting distributions of cell behaviors
      for six transcriptional cascades and three feed-forward circuits in mammalian
      cells. Our cascade predictions have only 1.6-fold mean error over a 261-fold mean
      range of fluorescence variation, owing primarily to calibrated measurements and
      piecewise-linear models. Predictions for three feed-forward circuits had a 2.0
      fold mean error on a 333-fold mean range, further demonstrating that EQuIP can
      scale to more complex systems. Such accurate predictions will foster reliable
      forward engineering of complex biological circuits from libraries of standardized
      devices. 

PMID- 25369268
TI  - Meningiomas: a comparative study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE
      for molecular imaging in mice.
AB  - PURPOSE: The goal of this study was to compare the tumor uptake kinetics and
      diagnostic value of three (68)Ga-DOTA-labeled somatostatin analogues ((68)Ga
      DOTATOC, (68)Ga-DOTANOC, and (68)Ga-DOTATATE) using PET/CT in a murine model with
      subcutaneous meningioma xenografts. METHODS: The experiment was performed with 16
      male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH
      157MN). (68)Ga-DOTATOC, (68)Ga-DOTANOC, and (68)Ga-DOTATATE were produced in a
      FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT
      scanner. The SUVmax of the liver and muscle, and the tumor-to-liver (T/L) and
      tumor-to-muscle (T/M) SUV ratios were computed. Kinetic analysis was performed
      using Logan graphical analysis for a two-tissue reversible compartmental model,
      and the volume of distribution (Vt) was determined. RESULTS: Hepatic SUVmax and
      Vt were significantly higher with (68)Ga-DOTANOC than with (68)Ga-DOTATOC and
      (68)Ga-DOTATATE. No significant differences between tracers were found for SUVmax
      in tumor or muscle. No differences were found in the T/L SUV ratio between (68)Ga
      DOTATATE and (68)Ga-DOTATOC, both of which had a higher fraction than (68)Ga
      DOTANOC. The T/M SUV ratio was significantly higher with (68)Ga-DOTATATE than
      with (68)Ga-DOTATOC and (68)Ga-DOTANOC. The Vt for tumor was higher with (68)Ga
      DOTATATE than with (68)Ga-DOTANOC and relatively similar to that of (68)Ga
      DOTATOC. CONCLUSIONS: This study demonstrates, for the first time, the ability of
      the three radiolabeled somatostatin analogues tested to image a human meningioma
      cell line. Although Vt was relatively similar with (68)Ga-DOTATATE and (68)Ga
      DOTATOC, uptake was higher with (68)Ga-DOTATATE in the tumor than with (68)Ga
      DOTANOC and (68)Ga-DOTATOC, suggesting a higher diagnostic value of (68)Ga
      DOTATATE for detecting meningiomas.

PMID- 25369269
TI  - Modeling warfare in social animals: a "chemical" approach.
AB  - We present here a general method for modelling the dynamics of battles among
      social animals. The proposed method exploits the procedures widely used to model
      chemical reactions, but still uncommon in behavioural studies. We applied this
      methodology to the interpretation of experimental observations of battles between
      two species of ants (Lasius neglectus and Lasius paralienus), but this scheme may
      have a wider applicability and can be extended to other species as well. We
      performed two types of experiment labelled as interaction and mortality. The
      interaction experiments are designed to obtain information on the combat dynamics
      and lasted one hour. The mortality ones provide information on the casualty rates
      of the two species and lasted five hours. We modelled the interactions among ants
      using a chemical model which considers the single ant individuals and fighting
      groups analogously to atoms and molecules. The mean-field behaviour of the model
      is described by a set of non-linear differential equations. We also performed
      stochastic simulations of the corresponding agent-based model by means of the
      Gillespie event-driven integration scheme. By fitting the stochastic trajectories
      with the deterministic model, we obtained the probability distribution of the
      reaction parameters. The main result that we obtained is a dominance phase
      diagram, that gives the average trajectory of a generic battle, for an arbitrary
      number of opponents. This phase diagram was validated with some extra
      experiments. With respect to other war models (e.g., Lanchester's ones), our
      chemical model considers all phases of the battle and not only casualties. This
      allows a more detailed description of the battle (with a larger number of
      parameters), allowing the development of more sophisticated models (e.g., spatial
      ones), with the goal of distinguishing collective effects from the strategic
      ones. 

PMID- 25369270
TI  - Triazolopyridines as selective JAK1 inhibitors: from hit identification to
      GLPG0634.
AB  - Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of
      multiple cytokines important in cellular function. Blockade of the JAK-STAT
      pathway with a small molecule has been shown to provide therapeutic
      immunomodulation. Having identified JAK1 as a possible new target for arthritis
      at Galapagos, the compound library was screened against JAK1, resulting in the
      identification of a triazolopyridine-based series of inhibitors represented by 3.
      Optimization within this chemical series led to identification of GLPG0634 (65,
      filgotinib), a selective JAK1 inhibitor currently in phase 2B development for RA
      and phase 2A development for Crohn's disease (CD). 

PMID- 25369271
TI  - Muscle pump in the vastus lateralis in the supine position in light prolonged
      exercise.
AB  - AIM: The purpose of this study was to examine whether the muscle pump in the
      supine position is attenuated during light prolonged exercise. METHODS: After
      rest for 5 min, constant-load exercise with 50% of peak oxygen uptake (VO2)
      determined by incremental exercises in the supine position was performed for 60
      min with a pedaling rate of 60 rpm. Total hemoglobin and myoglobin (total Hb) in
      the vastus lateralis was determined by using a near-infrared spectroscopy (NIRS)
      system. The instrument was operating at 2 Hz. VO2, heart rate (HR), mean blood
      pressure (MBP) and muscle deep temperature (Tm) were measured in the constant
      load exercise. RESULTS: After an increase at the onset of exercise, VO2 showed a
      steady state, HR showed a significant gradual increase and MBP significantly
      decreased. After an increase until 20 min of exercise, Tm showed a steady state.
      Level of total Hb increased until 20 min and showed a steady state in all
      subjects. Average Tm was significantly related to average total Hb (r=0.978).
      Total Hb oscillated, but its oscillation occasionally disappeared. Peak amplitude
      of oscillation in total Hb for 30 s after the start of exercise was significantly
      higher than that for 1 min before the end of exercise. CONCLUSION: The results
      suggest that the muscle pump operates in light exercise but is attenuated in the
      vastus lateralis in the supine position at the late phase of prolonged exercise.

PMID- 25369272
TI  - Modulation of TNF-alpha, TNF-alpha receptors and IL-6 after treatment with AM3 in
      professional cyclists.
AB  - AIM: Changes in IL-6, TNF-alpha, and TNF-alpha receptors - sTNFRI and sTNFRII -
      were evaluated in a group of professional cyclists treated with immunomodulator
      AM3 (Inmunoferon(r)) for 6 months of training and competition. METHODS: Sixteen
      male professional cyclists with a similar training program participated in the
      study which was designed as a randomized, placebo-controlled, double-blind
      clinical trial. Venous blood samples were collected in basal conditions, before
      beginning the supplementation program, and after 90 and 180 days of training and
      competition season. RESULTS: No significant differences in biochemical parameters
      or in IL-6 were evidenced between placebo and AM3-treated groups throughout the
      study. Plasma TNF-alpha levels significantly decreased (P<0.05) after 90 days of
      training in the AM3 treated group. TNF-alpha receptors increased during training
      season in both placebo and AM3 treated groups, although the increase was
      significantly higher (P<0.05) in the AM3 group with respect to the placebo group.
      CONCLUSION: The changes produced by regular training and competition were
      modified throughout the season by AM3 treatment which could reduce the
      inflammatory response to excessive exercise.

PMID- 25369273
TI  - Sport specific fitness status in junior water polo players--Playing position
      approach.
AB  - AIM: The aim of this investigation was to study the physical fitness differences
      between two qualitative levels of junior water polo players, with regard to their
      playing positions. METHODS: The sample (N.=54, males; 16-18 years of age)
      comprised 13 members of the Junior National Squad (JNS; 5 centres and 8 perimeter
      players), and 41 team athletes (TA; 11 centres and 30 perimeter players). The
      sample of variables included: body height, body mass, BMI and body fat
      percentage, 20 metres sprint swimming, maximal dynamometric force in eggbeater
      kick (DF), on-water vertical jump, drive-shoot-speed, and swimming-endurance-test
      (SET). Differences between JNS and TA were analysed by t-test for independent
      samples and by a magnitude-based Cohen's effect size (ES) statistic with modified
      qualitative descriptors. Forward conditional logistic regression (FCLR) was
      calculated to determine the impact of the physical fitness variables on the
      dichotomous criterion (JNS vs. TA). RESULTS: All variables were found to be
      reliable. The JNS perimeter players performed better (P<0.05) in SET, DF, and
      sprint-swimming than the TA perimeter players. No significant differences were
      found for centres. FCLR revealed drive-shoot-speed as the only significant
      predictor of qualitative level (Y=-12.925 + 1.188 * DSHOOT; OR: 1.023-1.380)
      CONCLUSION: Fitness capacities are more important as determinants of quality
      among perimeters than among centres. The results highlight the need for position
      specific training programmes in junior water polo.

PMID- 25369274
TI  - Etiology of musculoskeletal injuries in amateur breakdancers.
AB  - AIM: The aim of this study was to assess the incidence of musculoskeletal
      injuries in breakdancers and investigate the association with training habits.
      METHODS: Forty-six males and sixteen females completed a questionnaire regarding
      their training and competition habits (frequency, warm-up and stretching,
      strength training, protective equipment, move types and supervision) and the
      musculoskeletal injuries sustained as a result of breakdancing in the previous 12
      months. The effects of training habits and sex on injury rates were analyzed by a
      Mann-Whitney Test and a Kruskal-Wallis Test, while a stepwise linear regression
      analysis assessed the link between injury rates and quantitative risk factors.
      RESULTS: The injury rate was 4.02 injuries per 1000 h, with no significant
      difference between males and females (P>0.05). The main injuries affected were
      the knee (23.4%) and wrist (15.3%), and females were characterized by a
      significantly greater number of finger injuries and a lower number of shoulder
      injuries that males (P<0.05). In addition, of all the factors evaluated, only the
      amount of time spent performing breakdance training showed a significant
      association with injury rate (P<0.05). CONCLUSION: These results suggest that
      interventions should focus on protecting specific body parts and improving
      training quality and recovery.

PMID- 25369275
TI  - Sports injuries in Plus League volleyball players.
AB  - AIM: Although physical activity brings a range of lifelong health benefits, it
      may also lead to injuries that pose a significant threat to health. It is
      particularly noticeable in people involved in professional sports where sport
      related injuries commonly occur and are associated with intense exercise which
      aims to improve physical fitness. The article attempts to determine incidence of
      sports injuries reported by Plus League volleyball players, as well as to
      identify their most common types and causes. METHODS: The research project
      involved 90 Plus League volleyball players aged 18-37 with the average age of
      25.11 (SD+/-5.378). A method of diagnostic survey was applied to collect
      empirical data by means of questionnaire developed by the authors (researchers).
      The results were statistically analysed and verified with the analysis of
      variance (ANOVA) and chi2 test at the significance level (or critical P-value) of
      P<=0.05. RESULTS: Over 87% of the respondents suffered from at least one sport
      related injury. In total, 362 injuries occurred, on average 4.02 injuries per one
      volleyball player. The most common sports injuries involved ankle or talocrural
      joint (46 injuries), knee and lower leg muscles (30), interphalangeal
      articulations of fingers (30) as well as shoulder joint. More than half of the
      injuries (57%) occurred twice or three times. Volleyball players commonly sustain
      injuries through contact with an opposing player in competition. Sport-specific
      injuries may also occur due to exhaustion, lack of rest and undertreated
      injuries. CONCLUSION: The most common volleyball-related injuries are primarily
      talocrural joint, hand and shoulder injuries. Common types of injuries that can
      affect volleyball players include muscles, joints and ligaments injuries, sprains
      and strains as well as bruises. Most of these injuries are caused by exhaustion,
      contact with an opposing player during competition and fatigue. The incidence of
      sport-related injuries seems to be influenced by such factors as somatic
      features, jumping parameters and the length of professional volleyball career.

PMID- 25369276
TI  - The impact of functional training on postural stability and body composition in
      women over 60.
AB  - AIM: The aim of this study was to assess whether functional exercise improved
      postural stability and body composition in female subjects over 60 years of age.
      METHODS: Thirty women participated in this study, after being medically qualified
      for a 3-month functional exercise program. They underwent a series of tests
      twice, once before starting this functional exercise program, and once again
      after completing it. These tests consisted of anthropometric examination,
      stabilometry tests on a Biodex Balance System SD (BBS), and body composition
      analysis using a Tanita BC420 SMA. RESULTS: The results indicated an improvement
      in balance parameters among the group of participants between the first test and
      the second. Statistically significant differences were found in the results of
      the Postural Stability Test (PST) in static position without visual control
      protocols and the Fall Risk Test (FRT). In addition, a statistically significant
      reduction in body weight of 1.16 kg was noted, together with an associated
      decrease in BMI of 0.35. In terms of body content parameters, the participants'
      fat content was found to be significantly reduced, by approximately 1.26%. A
      Wilcoxon test also found a statistically significant (p=0.00002) increase in the
      content of muscle tissue between the first test and the second. CONCLUSION: The
      regime of functional training used in this study has a positive impact on the
      health of elderly females, helping to counteract involutional changes that lead
      to body imbalance and decreased muscle mass. Further research should seek to
      further optimize such a regime in this regard.

PMID- 25369277
TI  - Effect of reduced coenzyme Q10 (ubiquinol) supplementation on blood pressure and
      muscle damage during kendo training camp: a double-blind, randomized controlled
      study.
AB  - AIM: This randomized controlled study was designed to examine the effects of
      reduced coenzyme Q10 (ubiquinol; CoQ10) supplementation on blood pressure (BP)
      and exercise-induced muscle damage in kendo athletes during a 4-day kendo
      training camp. METHODS: In a double-blinded manner, 32 young kendo athletes were
      randomly assigned to supplement with either placebo or CoQ10 (600 mg) daily for
      11 days from 1 week prior to camp to end of camp. BP was measured every morning
      after waking up during the training camp. Blood samples were taken at 3 time
      points; 1 week and 1 day prior and upon completion of training camp at 17:30.
      Statistical analysis was performed by repeated-measures analysis of variance
      followed by Bonferroni/Dunn post-hoc tests. RESULTS: Before the training camp
      started, there were no differences in diastolic BP between these groups. However,
      after kendo training started, diastolic BP in the CoQ10 group was significantly
      lower than that in the placebo group (P<0.05). Plasma creatine kinase (CK) and
      myoglobin (Mb) concentrations were significantly increased in both groups during
      the camp (P<0.05), whereas there were no significant differences in CK and Mb
      between CoQ10 and placebo groups (CK: P=0.82, Mb: P=0.69). CONCLUSION: Oral
      supplementation with reduced form of CoQ10 (ubiquinol; Kaneka QHTM) showed a
      significant hypotensive effect in young male kendo athletes during a 4-day kendo
      training camp, although it did not significantly ameliorate kendo exercise
      induced muscle damage.

PMID- 25369278
TI  - Water polo throwing velocity and kinematics: differences between competitive
      levels in male players.
AB  - AIM: In water polo, throwing is one of the most important and frequently used
      technical skills for the player. There is no scientific literature that provides
      information about differences in throwing between elite and sub-elite water polo
      players. The aim of our study was to study differences in throwing velocities and
      kinematic variables in elite and sub-elite level male water polo players.
      METHODS: We considered the variables under standardized conditions during a
      typical motion, the five-meter shot (penalty). Thirty-four athletes from the
      Men's First Division Water Polo Championship and forty-two players participating
      in the National Fourth Division League, took part in the study. Video analysis
      measures were taken with high-speed digital cameras and the videos were analyzed
      offline with Dartfish 5.0 Pro. RESULTS: No correlation was found between body
      mass, height and throwing velocity. Elite players had higher values for ball
      speed (22.8+/-2.4 m/s for elite team and 18.4+/-1.7 m/s for sub-elite team;
      P=0.002) and greater elbow angle (157.5+/-10.3 degree for elite team versus
      146.7+/-8.9 degree for sub-elite team; P=0.002). In elite team the throwing time
      was lower (165.6+/-22.2 and 188.6+/-23.9 ms, respectively; P=0.05) and the
      shoulder angle was smaller (115.1+/-10.3 and 123.8+/-12.4 degree, respectively;
      P=0.03) than in sub-elite team. Head height was significantly greater in elite
      players (elite players 71.1+/-8.7 cm, sub-elite players 65.6+/-6.2 cm; P=0.03).
      CONCLUSION: Differences in kinematic characteristics between elite and sub-elite
      players were showed. Differences in elbow and shoulder action must be considered
      both in training and injury prevention.

PMID- 25369279
TI  - Is it possible to identify underlying cardiovascular risk in young trained
      military?
AB  - BACKGROUND: Exercise is an important tool in the prevention of cardiovascular
      risk. Counter-intuitively, elite athletes and military have been found to have
      high cardiovascular risk. This study aimed to identify underlying cardiovascular
      risk in young trained military using different parameters including the leptin:
      adiponectin (L:A) ratio. METHODS: Healthy military males (N.=54) participated in
      this study. Anthropometric and body composition were measured. After overnight
      fasting, the following parameters were determined: plasma lipid profile,
      electronegative-LDL, leptin and adiponectin concentrations. Data were expressed
      as median (25th and 75th percentiles). The relationship between variables was
      tested using the Spearman correlation test, with statistical significance set at
      P<0.05. RESULTS: Total cholesterol (143 [130-157] mg/dL), triglycerides (TG; 88.5
      [63-116] mg/dL) and LDL cholesterol (77.6 [68.8-94.5] mg/dL) plasma levels were
      adequate. However, all participants were found to have HDL cholesterol below 60
      mg/dL (43 [40-49] mg/dL) and 44% (N.=24) had a TG:HDL ratio (2.0 [1.4-2.9]) above
      2.0. The L:A ratio was higher than 0.32 for 29% (N.=16) of the participants. The
      main correlations observed were between waist circumference (WC) and WC:height
      ratio, with TG (r=0.37; r=0.56), TG:HDL ratio (r=0.41; r=0.36), HDL (r= -0.344;
      r= -0.26), and L:A ratio (r=0.25; r=0.46). CONCLUSIONS: Trained military men
      could be classified as at borderline cardiovascular risk when considering only
      their lipid profiles. However, this observation may be misleading, since lipid
      profiles are altered by very intense and long exercise. The L:A ratio be should
      be monitored more closely to establish whether a relationship exists between WC
      and WC:height and the L:A ratio has potential diagnostic.

PMID- 25369280
TI  - Changes in sleep quantity and efficiency in professional rugby union players
      during home based training and match-play.
AB  - : Adequate sleep is paramount to athlete recovery and performance, however little
      is know about the typical sleep patterns of professional rugby union players
      during home based training and match-play in the competitive season. AIM: The aim
      of the present study was to monitor changes in sleep quantity and efficiency of
      elite male rugby union players over a twelve night period, which included
      training and two competitive matches. METHODS: A total of ten elite male rugby
      union players from a selected team, participated in the study. Athletes sleep
      quantity and efficiency was monitored over a twelve night period using the
      Bodymedia sensewear units (BSU). RESULTS: There was a significant difference in
      sleep quantity (p<0.05) on game nights compared to non game night, with players
      sleeping less on game nights. Time to sleep on game nights was also significantly
      (p<0.05) later than non game nights. There was no significant difference in sleep
      efficiency or time at wake over the twelve night period. Sleep efficiency is
      defined as a percentage score calculated by incorporating movement and
      physiological measures over the sleep duration as determined by the BSU. Also
      there was no significant difference between sleep parameters on the game nights.
      The findings show players have significantly (p<0.05) reduced sleep following a
      home game, which is of concern considering the established negative influence of
      sleep deprivation on cognitive and physical performance. CONCLUSION: This data
      may assist coaching, medical and performance staff to develop and implement team
      and individualised sleep monitoring regimes to optimise training and on-field
      performance.

PMID- 25369281
TI  - Diminished anaerobic and aerobic exercise fitness in the hemoglobin E traits.
AB  - BACKGROUND: There is no information about the exercise performances of the
      hemoglobin E trait (Hb EA), which is the second most prevalent hemoglobinopathy
      found in Southeast Asia and Mediterranean. The purpose of the present study was
      to compare both anaerobic and aerobic exercise performances between young male
      subjects with Hb EA and with normal hemoglobin (A2A). METHODS: One hundred and
      twenty-two subjects underwent Hb EA Test screening, which revealed the presence
      of 17 subjects with Hb EA and 105 subjects with A2A. Thirteen subjects in each of
      the Hb EA and the normal hemoglobin groups were matched for race, age, height,
      weight, BMI, %body fat and physical activity profiles. All subjects performed the
      peak power output and anaerobic capacity tests using the Wingate protocol and the
      direct VO2max tests using a bicycle ergometer. The results were analyzed with the
      unpaired t-tests. RESULTS: The Hb EA subjects had lower (P<0.05, unpaired t-test)
      relative peak anaerobic power (15.58+/-0.44 W.kg-1, mean+/-SEM), relative
      anaerobic capacity (6.50+/-0.16 W.kg-1) and maximal oxygen uptake (VO2max)
      (27.39+/-1.65 mL.kg-1.min-1) when compared to normal hemoglobin group (17.39+/
      0.48 W.kg-1, 7.21+/-0.18 W.kg-1 and 33.05+/-1.59 mL.kg-1.min-1, respectively).
      CONCLUSIONS: The present study suggests that anaerobic exercise and aerobic
      exercise performances of the Hb EA subjects may be lower than matched normal
      hemoglobin subjects using the Wingate and the VO2max tests. However, the
      mechanisms of these results should be further investigated.

PMID- 25369282
TI  - Association of adenotonsillectomy with asthma outcomes in children: a
      longitudinal database analysis.
AB  - BACKGROUND: Childhood asthma and obstructive sleep apnea (OSA), both disorders of
      airway inflammation, were associated in recent observational studies. Although
      childhood OSA is effectively treated by adenotonsillectomy (AT), it remains
      unclear whether AT also improves childhood asthma. We hypothesized that AT, the
      first line of therapy for childhood OSA, would be associated with improved asthma
      outcomes and would reduce the usage of asthma therapies in children. METHODS AND
      FINDINGS: Using the 2003-2010 MarketScan database, we identified 13,506 children
      with asthma in the United States who underwent AT. Asthma outcomes during 1 y
      preceding AT were compared to those during 1 y following AT. In addition, 27,012
      age-, sex-, and geographically matched children with asthma without AT were
      included to examine asthma outcomes among children without known adenotonsillar
      tissue morbidity. Primary outcomes included the occurrence of a diagnostic code
      for acute asthma exacerbation (AAE) or acute status asthmaticus (ASA). Secondary
      outcomes included temporal changes in asthma medication prescriptions, the
      frequency of asthma-related emergency room visits (ARERs), and asthma-related
      hospitalizations (ARHs). Comparing the year following AT to the year prior, AT
      was associated with significant reductions in AAE (30.2%; 95% CI: 25.6%-34.3%;
      p<0.0001), ASA (37.9%; 95% CI: 29.2%-45.6%; p<0.0001), ARERs (25.6%; 95% CI:
      16.9%-33.3%; p<0.0001), and ARHs (35.8%; 95% CI: 19.6%-48.7%; p = 0.02).
      Moreover, AT was associated with significant reductions in most asthma
      prescription refills, including bronchodilators (16.7%; 95% CI: 16.1%-17.3%;
      p<0.001), inhaled corticosteroids (21.5%; 95% CI: 20.7%-22.3%; p<0.001),
      leukotriene receptor antagonists (13.4%; 95% CI: 12.9%-14.0%; p<0.001), and
      systemic corticosteroids (23.7%; 95% CI: 20.9%-26.5%; p<0.001). In contrast,
      there were no significant reductions in these outcomes in children with asthma
      who did not undergo AT over an overlapping follow-up period. Limitations of the
      MarketScan database include lack of information on race and obesity status. Also,
      the MarketScan database does not include information on children with public
      health insurance (i.e., Medicaid) or uninsured children. CONCLUSIONS: In a very
      large sample of privately insured children, AT was associated with significant
      improvements in several asthma outcomes. Contingent on validation through
      prospectively designed clinical trials, this study supports the premise that
      detection and treatment of adenotonsillar tissue morbidity may serve as an
      important strategy for improving asthma control. Please see later in the article
      for the Editors' Summary.

PMID- 25369285
TI  - Evaluation on activity of cytochrome p450 enzymes in turbot via a probe drug
      cocktail.
AB  - Cytochrome P450s (CYPs) are the main catalytic enzymes for metabolism by a
      variety of endogenous and exogenous substrates in mammals, fish, insects, etc. We
      evaluated the application of a multidrug cocktail on changes in CYP1, CYP2, and
      CYP3 activity in Turbot Scophthalmus maximus. The probe drugs were a combination
      of caffeine (5 mg/kg body weight), dapsone (5 mg/kg), and chlorzoxazone (10
      mg/kg). After a single intraperitoneal injection of the cocktail, the
      concentration of all three probe drugs in the plasma increased quickly to a peak
      and then decreased gradually over 24 h. Pharmacokinetic profiles of the three
      probe drugs were determined using a noncompartmental analysis, and the typical
      parameters were calculated. In the assay for CYP induction, pretreatment with
      rifampicin significantly reduced the typical pharmacokinetic metrics for caffeine
      and chlorzoxazone, but not dapsone, indicating that the activity of CYP1 and CYP2
      in turbot were induced by rifampicin.

PMID- 25369284
TI  - An interaction of renin-angiotensin and kallikrein-kinin systems contributes to
      vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro
      studies.
AB  - The kallikrein-kinin and renin-angiotensin systems interact at multiple levels.
      In the present study, we tested the hypothesis that the B1 kinin receptor (B1R)
      contributes to vascular hypertrophy in angiotensin II (ANG II)-induced
      hypertension, through a mechanism involving reactive oxygen species (ROS)
      generation and extracellular signal-regulated kinase (ERK1/2) activation. Male
      Wistar rats were infused with vehicle (control rats), 400 ng/Kg/min ANG II (ANG
      II rats) or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des
      Arg(9)-Leu(8)-bradykinin (ANGII+DAL rats), via osmotic mini-pumps (14 days) or
      received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats).
      After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg)
      184 +/- 5.9 vs 115 +/- 2.3], aortic hypertrophy; increased ROS generation [2
      hydroxyethidium/dihydroethidium (EOH/DHE): 21.8 +/- 2.7 vs 6.0 +/- 1.8] and
      ERK1/2 phosphorylation (% of control: 218.3 +/- 29.4 vs 100 +/- 0.25]. B1R
      expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas
      from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy,
      prevented ROS generation (EOH/DHE: 9.17 +/- 3.1) and ERK1/2 phosphorylation (137
      +/- 20.7%) in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC)
      stimulated with low concentrations (0.1 nM) of ANG II plus B1R agonist exhibited
      increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear
      antigen expression and [H3]leucine incorporation. At this concentration, neither
      ANG II nor the B1R agonist produced any effects when tested individually. The ANG
      II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 uM), B1R
      antagonist (10 uM) and Tiron (superoxide anion scavenger, 10 mM). These data
      suggest that B1R activation contributes to ANG II-induced aortic hypertrophy.
      This is associated with activation of redox-regulated ERK1/2 pathway that
      controls aortic smooth muscle cells growth. Our findings highlight an important
      cross-talk between the DABK and ANG II in the vascular system and contribute to a
      better understanding of the mechanisms involved in vascular remodeling in
      hypertension.

PMID- 25369286
TI  - Relationship of Dickkopf1 (DKK1) with cardiovascular disease and bone metabolism
      in Caucasian type 2 diabetes mellitus.
AB  - OBJECTIVES: Dickkopf-1 (DKK1) is a potent inhibitor of Wnt signalling, which
      exerts anabolic effects on bone and also takes part in the regulation of vascular
      cells. Our aims were to evaluate serum DKK1 in type 2 diabetes (T2DM) patients
      and to analyze its relationships with cardiovascular disease (CVD). We also
      evaluated the relationship between DKK1 and bone metabolism. DESIGN: We conducted
      a cross-sectional study in which we measured serum DKK1 (ELISA, Biomedica) in 126
      subjects: 72 patients with T2DM and 54 non-diabetic subjects. We analysed its
      relationship with clinical CVD, preclinical CVD expressed as carotid intima media
      thickness (IMT), and bone metabolism. RESULTS: T2DM patients with CVD (P = 0,026)
      and abnormal carotid IMT (P = 0,038) had higher DKK1 concentrations. DKK1 was
      related to the presence of CVD in T2DM, independently of the presence of risk
      factors for atherosclerosis. Therefore, for each increase of 28 pg/ml of serum
      DKK1 there was a 6,2% increase in the risk of CVD in T2DM patients. The ROC curve
      analysis to evaluate the usefulness of DKK1 as a marker for high risk of CVD
      showed an area under the curve of 0,667 (95% CI: 0,538-0,795; P = 0,016). In
      addition, there was a positive correlation between serum DKK1 and spine bone
      mineral density in the total sample (r =  0,183; P = 0,048). CONCLUSION: In
      summary, circulating DKK1 levels are higher in T2DM with CVD and are associated
      with an abnormal carotid IMT in this cross-sectional study. DKK1 may be involved
      in vascular disease of T2DM patients.

PMID- 25369287
TI  - How can inequalities in mortality be reduced? A quantitative analysis of 6 risk
      factors in 21 European populations.
AB  - BACKGROUND: Socioeconomic inequalities in mortality are one of the greatest
      challenges for health policy in all European countries, but the potential for
      reducing these inequalities is unclear. We therefore quantified the impact of
      equalizing the distribution of six risk factors for mortality: smoking,
      overweight, lack of physical exercise, lack of social participation, low income,
      and economic inactivity. METHODS: We collected and harmonized data on mortality
      and risk factors by educational level for 21 European populations in the early
      2000s. The impact of the risk factors on mortality in each educational group was
      determined using Population Attributable Fractions. We estimated the impact on
      inequalities in mortality of two scenarios: a theoretical upward levelling
      scenario in which inequalities in the risk factor were completely eliminated, and
      a more realistic best practice scenario, in which inequalities in the risk factor
      were reduced to those seen in the country with the smallest inequalities for that
      risk factor. FINDINGS: In general, upward levelling of inequalities in smoking,
      low income and economic inactivity hold the greatest potential for reducing
      inequalities in mortality. While the importance of low income is similar across
      Europe, smoking is more important in the North and East, and overweight in the
      South. On the basis of best practice scenarios the potential for reducing
      inequalities in mortality is often smaller, but still substantial in many
      countries for smoking and physical inactivity. INTERPRETATION: Theoretically,
      there is a great potential for reducing inequalities in mortality in most
      European countries, for example by equity-oriented tobacco control policies,
      income redistribution and employment policies. Although it is necessary to
      achieve substantial degrees of upward levelling to make a notable difference for
      inequalities in mortality, the existence of best practice countries with more
      favourable distributions for some of these risk factors suggests that this is
      feasible.

PMID- 25369288
TI  - Energy response calibration of photon-counting detectors using x-ray
      fluorescence: a feasibility study.
AB  - Accurate energy calibration is critical for the application of energy-resolved
      photon-counting detectors in spectral imaging. The aim of this study is to
      investigate the feasibility of energy response calibration and characterization
      of a photon-counting detector using x-ray fluorescence. A comprehensive Monte
      Carlo simulation study was performed using Geant4 Application for Tomographic
      Emission (GATE) to investigate the optimal technique for x-ray fluorescence
      calibration. Simulations were conducted using a 100 kVp tungsten-anode spectra
      with 2.7 mm Al filter for a single pixel cadmium telluride (CdTe) detector with 3
      * 3 mm(2) in detection area. The angular dependence of x-ray fluorescence and
      scatter background was investigated by varying the detection angle from 20
      degrees  to 170 degrees  with respect to the beam direction. The effects of the
      detector material, shape, and size on the recorded x-ray fluorescence were
      investigated. The fluorescent material size effect was considered with and
      without the container for the fluorescent material. In order to provide
      validation for the simulation result, the angular dependence of x-ray
      fluorescence from five fluorescent materials was experimentally measured using a
      spectrometer. Finally, eleven of the fluorescent materials were used for energy
      calibration of a CZT-based photon-counting detector. The optimal detection angle
      was determined to be approximately at 120 degrees  with respect to the beam
      direction, which showed the highest fluorescence to scatter ratio (FSR) with a
      weak dependence on the fluorescent material size. The feasibility of x-ray
      fluorescence for energy calibration of photon-counting detectors in the
      diagnostic x-ray energy range was verified by successfully calibrating the energy
      response of a CZT-based photon-counting detector. The results of this study can
      be used as a guideline to implement the x-ray fluorescence calibration method for
      photon-counting detectors in a typical imaging laboratory.

PMID- 25369291
TI  - Xenopsylla cheopis (Siphonaptera: Pulicidae) susceptibility to Deltamethrin in
      Madagascar.
AB  - The incidence of bubonic plague in Madagascar is high. This study reports the
      susceptibility of 32 different populations of a vector, the flea Xenopsylla
      cheopis (Siphonaptera: Pulicidae), to the insecticide Deltamethrin. Despite the
      use of Deltamethrin against fleas, plague epidemics have re-emerged in
      Madagascar. The majority of the study sites were located in the Malagasy
      highlands where most plague cases have occurred over the last 10 years. X.
      cheopis fleas were tested for susceptibility to Deltamethrin (0.05%): only two
      populations were susceptible to Deltamethrin, four populations were tolerant and
      26 populations were resistant. KD50 (50% Knock-Down) and KD90 (90% Knock-Down)
      times were determined, and differed substantially from 9.4 to 592.4 minutes for
      KD50 and 10.4 min to 854.3 minutes for KD90. Susceptibility was correlated with
      latitude, but not with longitude, history of insecticide use nor date of
      sampling. Combined with the number of bubonic plague cases, our results suggest
      that an immediate switch to an insecticide other than Deltamethrin is required
      for plague vector control in Madagascar. 

PMID- 25369289
TI  - Draft genome sequence analysis of a Pseudomonas putida W15Oct28 strain with
      antagonistic activity to Gram-positive and Pseudomonas sp. pathogens.
AB  - Pseudomonas putida is a member of the fluorescent pseudomonads known to produce
      the yellow-green fluorescent pyoverdine siderophore. P. putida W15Oct28, isolated
      from a stream in Brussels, was found to produce compound(s) with antimicrobial
      activity against the opportunistic pathogens Staphylococcus aureus, Pseudomonas
      aeruginosa, and the plant pathogen Pseudomonas syringae, an unusual
      characteristic for P. putida. The active compound production only occurred in
      media with low iron content and without organic nitrogen sources. Transposon
      mutants which lost their antimicrobial activity had the majority of insertions in
      genes involved in the biosynthesis of pyoverdine, although purified pyoverdine
      was not responsible for the antagonism. Separation of compounds present in
      culture supernatants revealed the presence of two fractions containing highly
      hydrophobic molecules active against P. aeruginosa. Analysis of the draft genome
      confirmed the presence of putisolvin biosynthesis genes and the corresponding
      lipopeptides were found to contribute to the antimicrobial activity. One cluster
      of ten genes was detected, comprising a NAD-dependent epimerase, an
      acetylornithine aminotransferase, an acyl CoA dehydrogenase, a short chain
      dehydrogenase, a fatty acid desaturase and three genes for a RND efflux pump. P.
      putida W15Oct28 genome also contains 56 genes encoding TonB-dependent receptors,
      conferring a high capacity to utilize pyoverdines from other pseudomonads. One
      unique feature of W15Oct28 is also the presence of different secretion systems
      including a full set of genes for type IV secretion, and several genes for type
      VI secretion and their VgrG effectors. 

PMID- 25369292
TI  - Epigenetic mechanisms in respiratory muscle dysfunction of patients with chronic
      obstructive pulmonary disease.
AB  - Epigenetic events are differentially expressed in the lungs and airways of
      patients with chronic obstructive pulmonary disease (COPD). Moreover, epigenetic
      mechanisms are involved in the skeletal (peripheral) muscle dysfunction of COPD
      patients. Whether epigenetic events may also regulate respiratory muscle
      dysfunction in COPD remains unknown. We hypothesized that epigenetic mechanisms
      would be differentially expressed in the main inspiratory muscle (diaphragm) of
      patients with COPD of a wide range of disease severity compared to healthy
      controls. In diaphragm muscle specimens (thoracotomy due to lung localized
      neoplasms) of sedentary patients with mild-to-moderate and severe COPD, with
      preserved body composition, and sedentary healthy controls, expression of muscle
      enriched microRNAs, histone acetyltransferases (HATs) and deacetylases (HDACs),
      total DNA methylation and protein acetylation, small ubiquitin-related modifier
      (SUMO) ligases, muscle-specific transcription factors, and muscle structure were
      explored. All subjects were also clinically evaluated: lung and muscle functions
      and exercise capacity. Compared to healthy controls, patients exhibited moderate
      airflow limitation and diffusion capacity, and reduced exercise tolerance and
      transdiaphragmatic strength. Moreover, in the diaphragm of the COPD patients,
      muscle-specific microRNA expression was downregulated, while HDAC4 and myocyte
      enhancer factor (MEF)2C protein levels were higher, and DNA methylation levels,
      muscle fiber types and sizes did not differ between patients and controls. In the
      main respiratory muscle of COPD patients with a wide range of disease severity
      and normal body composition, muscle-specific microRNAs were downregulated, while
      HDAC4 and MEF2C levels were upregulated. It is likely that these epigenetic
      events act as biological adaptive mechanisms to better overcome the continuous
      inspiratory loads of the respiratory system in COPD. These findings may offer
      novel therapeutic strategies to specifically target respiratory muscle
      dysfunction in patients with COPD. 

PMID- 25369294
TI  - A new organocatalytic concept for asymmetric alpha-alkylation of aldehydes.
AB  - The organocatalytic asymmetric alpha-alkylation of aldehydes by 1,6-conjugated
      addition of enamines to p-quinone methides is described. Employing a newly
      developed class of chiral secondary amine catalysts, alpha-diarylmethine
      substituted aldehydes with two contiguous stereocenters have been synthesized in
      a simple manner with good diastereocontrol and excellent enantioselectivity. 

PMID- 25369293
TI  - Health-related quality of life in older adult survivors of selected cancers: data
      from the SEER-MHOS linkage.
AB  - BACKGROUND: Research on health-related quality of life (HRQOL) among older adult
      cancer survivors is mostly confined to breast cancer, prostate cancer, colorectal
      cancer, and lung cancer, which account for 63% of all prevalent cancers. Much
      less is known about HRQOL in the context of less common cancer sites. METHODS:
      HRQOL was examined with the 36-Item Short Form Health Survey, version 1, and the
      Veterans RAND 12-Item Health Survey in patients with selected cancers (kidney
      cancer, bladder cancer, pancreatic cancer, upper gastrointestinal cancer, cancer
      of the oral cavity and pharynx, uterine cancer, cervical cancer, thyroid cancer,
      melanoma, chronic leukemia, non-Hodgkin lymphoma, and multiple myeloma) and in
      individuals without cancer on the basis of data linked from the Surveillance,
      Epidemiology, and End Results cancer registry system and the Medicare Health
      Outcomes Survey. Scale scores, Physical Component Summary (PCS) and Mental
      Component Summary (MCS) scores, and a utility metric (Short Form 6D/Veterans RAND
      6D), adjusted for sociodemographic characteristics and other chronic conditions,
      were calculated. A 3-point difference in the scale scores and a 2-point
      difference in the PCS and MCS scores were considered to be minimally important
      differences. RESULTS: Data from 16,095 cancer survivors and 1,224,549 individuals
      without a history of cancer were included. The results indicated noteworthy
      deficits in physical health status. Mental health was comparable, although scores
      for the Role-Emotional and Social Functioning scales were worse for patients with
      most types of cancer versus those without cancer. Survivors of multiple myeloma
      and pancreatic malignancies reported the lowest scores, with their PCS/MCS scores
      less than those of individuals without cancer by 3 or more points. CONCLUSIONS:
      HRQOL surveillance efforts revealed poor health outcomes among many older adults
      and specifically among survivors of multiple myeloma and pancreatic cancer.

PMID- 25369296
TI  - Two-dimensional V2O5 sheet network as electrode for lithium-ion batteries.
AB  - Two-dimensional V2O5 and manganese-doped V2O5 sheet network were synthesized by a
      one-step polymer-assisted chemical solution method and characterized by X-ray
      diffraction, scanning electron microscopy, transmission electron microscopy,
      thermal-gravimetric analysis, and galvanostatic discharge-charge analysis. The
      V2O5 particles were covered with thin carbon layers, which remained after
      decomposition of the polymer, forming a network-like sheet structure. This V2O5
      network exhibits a high capacity of about 300 and 600 mA.h/g at a current density
      of 100 mA/g when it was used as a cathode and anode, respectively. After doping
      with 5% molar ratio of manganese, the capacity of the cathode increases from 99
      to 165 mA.h/g at a current density of 1 A/g (~3 C). This unique network structure
      provides an interconnected transportation pathway for lithium ions. Improvement
      of electrochemical performance after doping manganese could be attributed to the
      enhancement of electronic conductivity. 

PMID- 25369295
TI  - Bacteriorhodopsin folds through a poorly organized transition state.
AB  - The folding mechanisms of helical membrane proteins remain largely uncharted.
      Here we characterize the kinetics of bacteriorhodopsin folding and employ phi
      value analysis to explore the folding transition state. First, we developed and
      confirmed a kinetic model that allowed us to assess the rate of folding from SDS
      denatured bacteriorhodopsin (bRU) and provides accurate thermodynamic information
      even under influence of retinal hydrolysis. Next, we obtained reliable phi-values
      for 16 mutants of bacteriorhodopsin with good coverage across the protein. Every
      phi-value was less than 0.4, indicating the transition state is not uniquely
      structured. We suggest that the transition state is a loosely organized ensemble
      of conformations. 

PMID- 25369298
TI  - Hepatocellular carcinoma: paving the road for further developments.

PMID- 25369297
TI  - Galectin-3 up-regulation in hypoxic and nutrient deprived microenvironments
      promotes cell survival.
AB  - Galectin-3 (gal-3) is a beta-galactoside binding protein related to many tumoral
      aspects, e.g. angiogenesis, cell growth and motility and resistance to cell
      death. Evidence has shown its upregulation upon hypoxia, a common feature in
      solid tumors such as glioblastoma multiformes (GBM). This tumor presents a unique
      feature described as pseudopalisading cells, which accumulate large amounts of
      gal-3. Tumor cells far from hypoxic/nutrient deprived areas express little, if
      any gal-3. Here, we have shown that the hybrid glioma cell line, NG97ht,
      recapitulates GBM growth forming gal-3 positive pseudopalisades even when cells
      are grafted subcutaneously in nude mice. In vitro experiments were performed
      exposing these cells to conditions mimicking tumor areas that display oxygen and
      nutrient deprivation. Results indicated that gal-3 transcription under hypoxic
      conditions requires previous protein synthesis and is triggered in a HIF-1alpha
      and NF-kappaB dependent manner. In addition, a significant proportion of cells
      die only when exposed simultaneously to hypoxia and nutrient deprivation and
      demonstrate ROS induction. Inhibition of gal-3 expression using siRNA led to
      protein knockdown followed by a 1.7-2.2 fold increase in cell death. Similar
      results were also found in a human GBM cell line, T98G. In vivo, U87MG gal-3
      knockdown cells inoculated subcutaneously in nude mice demonstrated decreased
      tumor growth and increased time for tumor engraftment. These results indicate
      that gal-3 protected cells from cell death under hypoxia and nutrient deprivation
      in vitro and that gal-3 is a key factor in tumor growth and engraftment in
      hypoxic and nutrient-deprived microenvironments. Overexpression of gal-3, thus,
      is part of an adaptive program leading to tumor cell survival under these
      stressing conditions. 

PMID- 25369299
TI  - Molecular profiling of liver tumors: classification and clinical translation for
      decision making.
AB  - Hepatocellular carcinoma (HCC) is a complex disease with a dismal prognosis.
      Consequently, a translational approach is required to personalized clinical
      decision making to improve survival of HCC patients. Molecular signatures from
      cirrhotic livers and single nucleotide polymorphism have been linked with HCC
      occurrence. Identification of high-risk populations will be useful to design
      chemopreventive trials. In addition, molecular signatures derived from tumor and
      nontumor samples are associated with early tumor recurrence due to metastasis and
      late tumor recurrence due to de novo carcinogenesis after curative treatment,
      respectively. Identification of patients with a high risk of relapse will guide
      adjuvant randomized trials. The genetic landscape drawn by next-generation
      sequencing has highlighted the genomic diversity of HCC. Genetic drivers
      recurrently mutated belong to different signaling pathways including telomere
      maintenance, cell-cycle regulators, chromatin remodeling, Wnt/b-catenin,
      RAS/RAF/MAPK kinase, and AKT/mTOR pathway. These cancer genes will be ideally
      targeted by biotherapies as a paradigm of stratified medicine adapted to tumor
      biology. 

PMID- 25369300
TI  - Immune control in hepatocellular carcinoma development and progression: role of
      stromal cells.
AB  - Immune control of hepatocellular carcinoma (HCC) is executed by effector immune
      cells, which efficiently eliminate malignant transformed cells. However,
      progression of HCC clearly documents failure of tumor immune control, which led
      to the concept of immune subversion by the tumor environment.Particularly tumor
      associated stromal cells cooperate within an inflammatory network, which is
      responsible for immune privilege. The stromal cell composition matures during
      tumor growth and is derived from surrounding noncancerous tissue or from
      circulating cells recruited to the tumor site. Therefore, immunosuppressive
      stromal cells represent heterogeneous cell lineages, including myeloid cells,
      lymphocytes, endothelial cells, and fibroblasts, which interact by direct cell
      contact, secretion of soluble factors, or production of extracellular matrix. As
      the stromal cells determine tumor immune control and clinical outcome of HCC,
      they represent a promising target for cancer immunotherapy. 

PMID- 25369301
TI  - Hepatocellular carcinoma screening and diagnosis.
AB  - All the major liver disease societies have recommended screening for
      hepatocellular carcinoma (HCC). The target population for HCC screening has been
      defined by cost-efficacy analyses and by risk scores. Risk scores have been
      developed for patients with hepatitis B, regardless of the presence of cirrhosis,
      and for other patients with cirrhosis. Screening is with ultrasound; however, in
      Asia biomarkers are also used. The additional value of biomarkers has not been
      demonstrated. The ideal screening interval is 6 months; in Japan shorter
      intervals are used. Screening detects small lesions that require confirmation of
      HCC. There are radiological criteria that help determine whether a biopsy is
      necessary. Special stains can determine whether a lesion that closely resembles
      normal or dysplastic tissue is HCC. All these tools should be used in the
      management of patients undergoing HCC screening. 

PMID- 25369302
TI  - Imaging techniques for the diagnosis of hepatocellular carcinoma and the
      evaluation of response to treatment.
AB  - Imaging plays a critical role in the diagnosis of hepatocellular carcinoma (HCC).
      In the USA, non-invasive imaging based diagnosis of HCC has largely replaced
      biopsy because of the high specificity and positive predictive value of imaging
      features for HCC. Because of the important role of imaging and the need to
      promote standardization of the management of HCC, several imaging-based
      algorithms for the diagnosis of HCC in at-risk patients have been
      developed.Imaging also plays a vital role in the assessment of HCC response to
      locoregional therapies (LRT) such as ablative and endovascular therapies.
      Standard imaging response criteria of solid tumors that rely solely on change in
      tumor size for determination of therapeutic success are not applicable to HCC
      undergoing LRT. Therefore, several systems have been developed over the years to
      objectively evaluate HCC response to LRT.In this review, we will describe major
      and ancillary imaging features of HCC, how these features are incorporated into
      the various imaging based algorithms, discuss the differences between algorithms,
      and address the emerging role of new imaging techniques and contrast agents in
      the diagnosis of HCC. We will also discuss the importance of assessment of HCC
      response to LRT, describe patterns of imaging response to the various therapies
      including newer volumetric and functional response measures, and examine and
      compare proposed response criteria of HCC to LRT. 

PMID- 25369303
TI  - Early hepatocellular carcinoma on the procrustean bed of ablation, resection, and
      transplantation.
AB  - In the treatment of early hepatocellular carcinoma (HCC), resection ablation and
      transplantation have had excellent initial success. Choices have to be based on a
      broad and long-term vision integrating-besides patients' interests-the
      community's needs and resources. In this scenario, guidelines such as the
      Barcelona Clinic Liver Cancer (BCLC) staging system can be viewed as a hideous
      frame (symbolized by the myth of Procrustes, Poseidon's son who stretched or
      maimed travelers to fit into his bed), or as a useful structure against which
      personalized or innovative treatments must be reality checked. In this article,
      the latter view is taken: For resection, portal hypertension must still represent
      a powerful caveat, particularly because of poor long-term results. Expansion of
      the criteria may instead be explored for multiple tumors and vascular invasion,
      where good indications can consistently be selected in expert surgical centers.
      For ablation, competitive results can be obtained although a small, but
      appreciable proportion of patients with early vascular invasion (~ 10%), as they
      could probably benefit from anatomical resections. Conversely, ablative
      techniques overcoming the location and size limitations are developing and may
      prove competitive. For transplantation, several equivalent careful expansions of
      Milan's Criteria can be accepted, but as more patients have access to the waiting
      list-often prioritized on non-HCC indications-current allocation models prove to
      be insufficient, if not plainly inequitable, and should be revised. 

PMID- 25369304
TI  - Recent advances in the prevention of hepatocellular carcinoma recurrence.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide.
      Early-stage HCC can be curatively treated, but the recurrence rate remains high.
      To date, adjuvant treatments have not proven effective in preventing HCC
      recurrence after curative treatment. Although early studies explored the
      potential of vitamin K2, retinoid, chemotherapy, and recently, sorafenib, none of
      the studies reported successful outcomes. Several new lines of evidence have
      emerged to support the use of novel antiviral agents for preventing the
      recurrence of virus-related HCC after curative treatment. In this review, the
      authors provide a thorough overview of the various adjuvant treatments that have
      been attempted or are being considered for trial. 

PMID- 25369305
TI  - Transarterial chemoembolization and radioembolization.
AB  - Transarterial chemoembolization (TACE) and radioembolization (RE) are frequently
      used to treat patients with hepatocellular carcinoma who cannot receive curative
      therapies. Transarterial chemoembolization is a heterogeneous group of
      procedures; based on two positive clinical trials and three meta-analyses,
      conventional TACE is the standard of care for patients in the intermediate stage.
      Transarterial chemoembolization with drug-eluting beads has been recently
      introduced as a more standardized way of performing TACE with similar outcomes
      and less systemic effects. Radioembolization is a form of brachytherapy in which
      microspheres are used as a source of internal radiation. Evidence supporting the
      use of RE derives from consistent, large-cohort series involving patients with
      more advanced hepatocellular carcinoma, not suitable for TACE or for those who
      have failed TACE. Transarterial chemoembolization and RE should not be considered
      competing therapies, but rather complementary tools. The clinical indications for
      TACE and RE will be further refined as results of ongoing large-scale studies
      become available. 

PMID- 25369306
TI  - Systemic therapy for hepatocellular carcinoma: the issue of treatment stage
      migration and registration of progression using the BCLC-refined RECIST.
AB  - Recent advancements have improved the management of patients with liver cancer.
      Results of studies have informed how to stage and decide the optimal treatment
      option for each patient with an adequate balance between risks and benefits. The
      Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy has been
      widely endorsed for this purpose. This is not a rigid system: One of the key
      aspects in the management of patients is the optimal timing for systemic
      treatment initiation and for declaring tumor progression and/or treatment
      failure. Some patients at intermediate or even early stage may be considered for
      systemic therapy as options of higher priority may have failed or may not be
      feasible. Sorafenib is the sole systemic agent that has shown efficacy in phase 3
      trials. Other agents (sunitinib, brivanib, linifanib, everolimus, ramucirumab)
      have failed in terms of safety and/or survival benefit. Optimal sorafenib
      administration and adequate adherence of the patients are crucial requirements to
      obtain the benefits of the drug. Because development of adverse events has been
      shown to correlate with better outcome, careful dose adjustments should be in
      place while avoiding unnecessary treatment interruption. Furthermore, recent
      studies have shown that progression at imaging may not translate in poor
      prognosis and that treatment beyond progression may be considered if there is no
      option for a second-line research trial.In this review, the authors examine all
      of the controversial aspects that affect treatment initiation and maintenance,
      how response to treatment should be evaluated, and define the needs that are
      faced by current research. 

PMID- 25369308
TI  - Histological changes in nontumoral liver secondary to radioembolization of
      hepatocellular carcinoma with yttrium 90-impregnated microspheres: report of two
      cases.
AB  - Transarterial radioembolization (TARE) with yttrium-90 is a minimally invasive
      locoregional therapy for hepatocellular carcinoma (HCC), and involves selective
      delivery of glass or resin microspheres impregnated with radioactive yttrium-90
      into small arteries preferentially supplying the tumor for tumoricidal effect
      thus sparing the nontumoral liver, or into lobar artery to induce atrophy and
      contralateral hypertrophy. Clinically, post-TARE a small proportion of cases
      develop radioembolization-induced liver disease. Histological changes of TARE on
      nontumoral liver parenchyma have not been well characterized. Herein, we report
      two cases of liver resections for HCC post-TARE, and describe the histological
      changes in nontumoral liver parenchyma. 

PMID- 25369307
TI  - Cholangiocarcinoma: molecular pathways and therapeutic opportunities.
AB  - Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy with limited
      treatment options and low survival rates. Currently, there are no curative
      medical therapies for CCA. Recent advances have enhanced our understanding of the
      genetic basis of this disease, and elucidated therapeutically relevant targets.
      Therapeutic efforts in development are directed at several key pathways due to
      genetic aberrations including receptor tyrosine kinase pathways, mutant IDH
      enzymes, the PI3K-AKT-mTOR pathway, and chromatin remodeling networks. A highly
      desmoplastic, hypovascular stroma is characteristic of CCAs and recent work has
      highlighted the importance of targeting this pathway via stromal myofibroblast
      depletion. Future efforts should concentrate on combination therapies with action
      against the cancer cell and the surrounding tumor stroma. As the mutational
      landscape of CCA is being illuminated, molecular profiling of patient tumors will
      enable identification of specific mutations and the opportunity to offer
      directed, personalized treatment options. 

PMID- 25369312
TI  - The Southern Ocean ecosystem under multiple climate change stresses--an
      integrated circumpolar assessment.
AB  - A quantitative assessment of observed and projected environmental changes in the
      Southern Ocean (SO) with a potential impact on the marine ecosystem shows: (i)
      large proportions of the SO are and will be affected by one or more climate
      change processes; areas projected to be affected in the future are larger than
      areas that are already under environmental stress, (ii) areas affected by changes
      in sea-ice in the past and likely in the future are much larger than areas
      affected by ocean warming. The smallest areas (<1% area of the SO) are affected
      by glacier retreat and warming in the deeper euphotic layer. In the future,
      decrease in the sea-ice is expected to be widespread. Changes in iceberg impact
      resulting from further collapse of ice-shelves can potentially affect large parts
      of shelf and ephemerally in the off-shore regions. However, aragonite
      undersaturation (acidification) might become one of the biggest problems for the
      Antarctic marine ecosystem by affecting almost the entire SO. Direct and indirect
      impacts of various environmental changes to the three major habitats, sea-ice,
      pelagic and benthos and their biota are complex. The areas affected by
      environmental stressors range from 33% of the SO for a single stressor, 11% for
      two and 2% for three, to <1% for four and five overlapping factors. In the
      future, areas expected to be affected by 2 and 3 overlapping factors are equally
      large, including potential iceberg changes, and together cover almost 86% of the
      SO ecosystem. 

PMID- 25369315
TI  - Nowcasting and forecasting the monthly food stamps data in the US using online
      search data.
AB  - We propose the use of Google online search data for nowcasting and forecasting
      the number of food stamps recipients. We perform a large out-of-sample
      forecasting exercise with almost 3000 competing models with forecast horizons up
      to 2 years ahead, and we show that models including Google search data
      statistically outperform the competing models at all considered horizons. These
      results hold also with several robustness checks, considering alternative
      keywords, a falsification test, different out-of-samples, directional accuracy
      and forecasts at the state-level. 

PMID- 25369316
TI  - Application of high-frequency Granger causality to analysis of epileptic seizures
      and surgical decision making.
AB  - OBJECTIVE: In recent decades intracranial EEG (iEEG) recordings using increasing
      numbers of electrodes, higher sampling rates, and a variety of visual and
      quantitative analyses have indicated the presence of widespread, high frequency
      ictal and preictal oscillations (HFOs) associated with regions of seizure onset.
      Seizure freedom has been correlated with removal of brain regions generating
      pathologic HFOs. However, quantitative analysis of preictal HFOs has seldom been
      applied to the clinical problem of planning the surgical resection. We performed
      Granger causality (GC) analysis of iEEG recordings to analyze features of
      preictal seizure networks and to aid in surgical decision making. METHODS: Ten
      retrospective and two prospective patients were chosen on the basis of
      individually stereotyped seizure patterns by visual criteria. Prospective
      patients were selected, additionally, for failure of those criteria to resolve
      apparent multilobar ictal onsets. iEEG was recorded at 500 or 1,000 Hz, using up
      to 128 surface and depth electrodes. Preictal and early ictal GC from individual
      electrodes was characterized by the strength of causal outflow, spatial
      distribution, and hierarchical causal relationships. RESULTS: In all patients we
      found significant, widespread preictal GC network activity at peak frequencies
      from 80 to 250 Hz, beginning 2-42 s before visible electrographic onset. In the
      two prospective patients, GC source/sink comparisons supported the exclusion of
      early ictal regions that were not the dominant causal sources, and contributed to
      planning of more limited surgical resections. Both patients have a class 1
      outcome at 1 year. SIGNIFICANCE: GC analysis of iEEG has the potential to
      increase understanding of preictal network activity, and to help improve surgical
      outcomes in cases of otherwise ambiguous iEEG onset.

PMID- 25369313
TI  - PI3K signaling and Stat92E converge to modulate glial responsiveness to axonal
      injury.
AB  - Glial cells are exquisitely sensitive to neuronal injury but mechanisms by which
      glia establish competence to respond to injury, continuously gauge neuronal
      health, and rapidly activate reactive responses remain poorly defined. Here, we
      show glial PI3K signaling in the uninjured brain regulates baseline levels of
      Draper, a receptor essential for Drosophila glia to sense and respond to axonal
      injury. After injury, Draper levels are up-regulated through a Stat92E-modulated,
      injury-responsive enhancer element within the draper gene. Surprisingly,
      canonical JAK/STAT signaling does not regulate draper expression. Rather, we find
      injury-induced draper activation is downstream of the Draper/Src42a/Shark/Rac1
      engulfment signaling pathway. Thus, PI3K signaling and Stat92E are critical in
      vivo regulators of glial responsiveness to axonal injury. We provide evidence for
      a positive auto-regulatory mechanism whereby signaling through the injury
      responsive Draper receptor leads to Stat92E-dependent, transcriptional activation
      of the draper gene. We propose that Drosophila glia use this auto-regulatory loop
      as a mechanism to adjust their reactive state following injury. 

PMID- 25369317
TI  - Clinical presentation and management of severe Ebola virus disease.
AB  - Clinicians caring for patients infected with Ebola virus must be familiar not
      only with screening and infection control measures but also with management of
      severe disease. By integrating experience from several Ebola epidemics with best
      practices for managing critical illness, this report focuses on the clinical
      presentation and management of severely ill infants, children, and adults with
      Ebola virus disease. Fever, fatigue, vomiting, diarrhea, and anorexia are the
      most common symptoms of the 2014 West African outbreak. Profound fluid losses
      from the gastrointestinal tract result in volume depletion, metabolic
      abnormalities (including hyponatremia, hypokalemia, and hypocalcemia), shock, and
      organ failure. Overt hemorrhage occurs infrequently. The case fatality rate in
      West Africa is at least 70%, and individuals with respiratory, neurological, or
      hemorrhagic symptoms have a higher risk of death. There is no proven antiviral
      agent to treat Ebola virus disease, although several experimental treatments may
      be considered. Even in the absence of antiviral therapies, intensive supportive
      care has the potential to markedly blunt the high case fatality rate reported to
      date. Optimal treatment requires conscientious correction of fluid and
      electrolyte losses. Additional management considerations include searching for
      coinfection or superinfection; treatment of shock (with intravenous fluids and
      vasoactive agents), acute kidney injury (with renal replacement therapy), and
      respiratory failure (with invasive mechanical ventilation); provision of
      nutrition support, pain and anxiety control, and psychosocial support; and the
      use of strategies to reduce complications of critical illness. Cardiopulmonary
      resuscitation may be appropriate in certain circumstances, but extracorporeal
      life support is not advised. Among other ethical issues, patients' medical needs
      must be carefully weighed against healthcare worker safety and infection control
      concerns. However, meticulous attention to the use of personal protective
      equipment and strict adherence to infection control protocols should permit the
      safe provision of intensive treatment to severely ill patients with Ebola virus
      disease. 

PMID- 25369318
TI  - Rehabilitation of face-processing skills in an adolescent with prosopagnosia:
      Evaluation of an online perceptual training programme.
AB  - In this paper we describe the case of EM, a female adolescent who acquired
      prosopagnosia following encephalitis at the age of eight. Initial
      neuropsychological and eye-movement investigations indicated that EM had profound
      difficulties in face perception as well as face recognition. EM underwent 14
      weeks of perceptual training in an online programme that attempted to improve her
      ability to make fine-grained discriminations between faces. Following training,
      EM's face perception skills had improved, and the effect generalised to untrained
      faces. Eye-movement analyses also indicated that EM spent more time viewing the
      inner facial features post-training. Examination of EM's face recognition skills
      revealed an improvement in her recognition of personally-known faces when
      presented in a laboratory-based test, although the same gains were not noted in
      her everyday experiences with these faces. In addition, EM did not improve on a
      test assessing the recognition of newly encoded faces. One month after training,
      EM had maintained the improvement on the eye-tracking test, and to a lesser
      extent, her performance on the familiar faces test. This pattern of findings is
      interpreted as promising evidence that the programme can improve face perception
      skills, and with some adjustments, may at least partially improve face
      recognition skills.

PMID- 25369319
TI  - Universal thermodynamics at the liquid-vapor critical point.
AB  - For 68 fluids that include hydrogen bonding and quantum fluids, the fugacity
      coefficient that defines the residual chemical potential adopts a near universal
      value of 2/3 at the critical point. More precisely, the reciprocal of the
      fugacity coefficient equals 1.52 +/- 0.02 and includes fluids as diverse as
      helium (1.50), dodecafluoropentane (1.50), and water (1.53). For 65 classical
      fluids, a dimensionless thermal pressure coefficient and internal pressure attain
      critical values of 1.88 +/- 0.11 and 1.61 +/- 0.11, respectively. From equations
      of state, values of these new critical constants have been calculated and agree
      favorably with experimental values. Specifically, for the critical fugacity
      coefficient, the following results were obtained for its reciprocal: van der
      Waals (1.44), lattice gas (1.43), scaled particle theory (1.46), and the Redlich
      Kwong eq (1.50). The semiempirical Redlich-Kwong equation is also the most
      accurate for the thermal pressure coefficient (1.86) and internal pressure
      (1.53). Physical interpretations of these results are discussed as well as their
      implications for other critical phenomena. 

PMID- 25369320
TI  - Detection of subclinical atherosclerosis in asymptomatic subjects using
      ultrasound radiofrequency-tracking technology.
AB  - OBJECTIVE: Atherosclerosis is a chronic and systemic disease and its
      developmental process involves the synergism of multiple risk factors such as
      hypertension, dyslipidemia, diabetes, obesity and smoking. The diagnosis of
      subclinical atherosclerosis is essential for strategic guidance towards suitable
      treatments and efficient prevention against acute cardiovascular events. This
      study employed ultrasound radiofrequency (RF) tracking technology to characterize
      human carotid arteries in vivo in terms of intima-media thickness (IMT) and
      artery stiffness, and evaluated the statistical correlation between carotid IMT
      and stiffness, and the number of risk factors for atherosclerosis. METHODS: A
      total of 160 asymptomatic subjects were enrolled. Ultrasound RF-tracking
      technology was employed to acquire carotid IMT and stiffness parameters: maximum
      IMT ((MAX)IMT), RF Quality IMT ((RF)QIMT), distensibility coefficient (DC),
      compliance coefficient (CC), alphaindex, beta index and local pulse wave velocity
      (PWVbeta). The subjects were categorized in four groups in terms of the number of
      risk factors: 'zero', 'single', 'double', and 'multiple', and statistical
      analyses of carotid IMT and stiffness parameters were performed between these
      different groups. RESULTS: The subjects (n = 145) with (MAX)IMT smaller than 1.0
      mm matched the IMT criteria for non-atherosclerosis and were named as NA
      subjects. Spearman's rho correlation analysis of the whole group and the NA
      subjects both showed that (MAX)IMT correlated positively with (RF)QIMT, alpha,
      beta, and PWVbeta, and negatively with DC and CC (p<0.01). The analysis of
      covariance of NA-subjects showed significant differences between subjects with
      and without risk factors, and also showed significant differences between the
      'zero', 'single', 'double', and 'multiple' groups. CONCLUSIONS: The carotid IMT
      and stiffness parameters obtained by the ultrasound RF-tracking technology were
      demonstrated to possess significant statistical correlation with the number of
      risk factors from 160 subjects, and these anatomical and mechanical parameters
      may potentially be used together with the IMT criteria to support subclinical
      atherosclerosis diagnosis.

PMID- 25369321
TI  - Cardioprotective effects of melatonin against myocardial injuries induced by
      chronic intermittent hypoxia in rats.
AB  - Obstructive sleep apnea (OSA) associated with chronic intermittent hypoxia (CIH)
      increases the morbidity and mortality of ischemic heart disease in patients. Yet,
      there is a paucity of preventive measures targeting the pathogenesis of CIH
      induced myocardial injury. We examined the cardioprotective effect of melatonin
      against the inflammation, fibrosis and the deteriorated sarcoplasmic reticulum
      (SR) Ca(2+) homeostasis, and ischemia/reperfusion (I/R)-induced injury
      exacerbated by CIH. Adult male Sprague Dawley rats that had received a daily
      injection of melatonin (10 mg/kg) or vehicle were exposed to CIH treatment
      mimicking a severe OSA condition for 4 wk. Systolic pressure, heart weights, and
      malondialdehyde were significantly increased in hypoxic rats but not in the
      melatonin-treated group, when compared with the normoxic control. Levels of the
      expression of inflammatory cytokines (TNF-alpha, IL-6, and COX-2) and fibrotic
      markers (PC1 and TGF-beta) were significantly elevated in the hypoxic group but
      were normalized by melatonin. Additionally, infarct size of isolated hearts with
      regional I/R was substantial in the hypoxic group treated with vehicle but not in
      the melatonin-treated group. Moreover, melatonin treatment mitigated the SR
      Ca(2+) homeostasis in the cardiomyocyte during I/R with (i) Ca(2+) overloading,
      (ii) decreased SR-Ca(2+) content, (iii) lowered expression and activity of Ca(2+)
      -handling proteins (SERCA2a and NCX1),and (iv) decreased expressions of CAMKII
      and phosphorylated eNOS(ser1177). Furthermore, melatonin ameliorated the level of
      expression of antioxidant enzymes (CAT and MnSOD) and NADPH oxidase (p22 and
      NOX2). Results support a prophylactic usage of melatonin in OSA patients, which
      protects against CIH-induced myocardial inflammation and fibrosis with impaired
      SR-Ca(2+) handling and exacerbated I/R injury.

PMID- 25369322
TI  - Molecular insights of oxidation process of iron nanoparticles: spectroscopic,
      magnetic, and microscopic evidence.
AB  - Oxidation behavior of nano-Fe(0) particles in an anoxic environment was
      determined using different state-of-the-art analytical approaches, including high
      resolution transmission electron microscopy (HR-TEM) combined with energy
      filtered transmission electron microscopy (EFTEM), X-ray absorption spectroscopy
      (XAS), and magnetic measurements. Oxidation in controlled experiments was
      compared in standard double distilled (DD) water, DD water spiked with
      trichloroethene (TCE), and TCE contaminated site water. Using HR-TEM and EFTEM,
      we observed a surface oxide layer (~3 nm) formed immediately after the particles
      were exposed to water. XAS analysis followed the dynamic change in total metallic
      iron concentration and iron oxide concentration for the experimental duration of
      35 days. The metallic iron concentration in nano-Fe(0) particles exposed to
      water, was ~40% after 35 days; in contrast, the samples containing TCE were
      reduced to ~15% and even to nil in the case of TCE contaminated site water,
      suggesting that the contaminants enhance the oxidation of nano-Fe(0). Frequency
      dependence measurements confirmed the formation of superparamagnetic particles in
      the system. Overall, our results suggest that nano-Fe(0) oxidized via the Fe(0) -
      Fe(OH)2 - Fe3O4 - (gamma-Fe2O3) route and the formation of superparamagnetic
      maghemite nanoparticles due to disruption of the surface oxide layer. 

PMID- 25369323
TI  - Development of a blocking ELISA based on a monoclonal antibody against a
      predominant epitope in non-structural protein 3B2 of foot-and-mouth disease virus
      for differentiating infected from vaccinated animals.
AB  - A monoclonal antibody (McAb) against non-structural protein (NSP) 3B of foot
      mouth-disease virus (FMDV) (3B4B1) was generated and shown to recognize a
      conserved epitope spanning amino acids 24-32 of 3B (GPYAGPMER) by peptide
      screening ELISA. This epitope was further shown to be a unique and predominant B
      cell epitope in 3B2, as sera from animals infected with different serotypes of
      FMDV blocked the ability of McAb 3B4B1 to bind to NSP 2C3AB. Also, a polyclonal
      antibody against NSP 2C was produced in a rabbit vaccinated with 2C epitope
      regions expressed in E. coli. Using McAb 3B4B1 and the 2C polyclonal antibody, a
      solid-phase blocking ELISA (SPB-ELISA) was developed for the detection of
      antibodies against NSP 2C3AB to distinguish FMDV-infected from vaccinated animals
      (DIVA test). The parameters for this SPB-ELISA were established by screening
      panels of sera of different origins. Serum samples with a percent inhibition (PI)
      greater than or equal to 46% were considered to be from infected animals, and a
      PI lower than 46% was considered to indicate a non-infected animal. This test
      showed a similar performance as the commercially available PrioCHECK NS ELISA.
      This is the first description of the conserved and predominant GPYAGPMER epitope
      of 3B and also the first report of a DIVA test for FMDV NSP 3B based on a McAb
      against this epitope. 

PMID- 25369324
TI  - Distinct role of CD86 polymorphisms (rs1129055, rs17281995) in risk of cancer:
      evidence from a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Previous studies concerning the role of CD86
      polymorphisms (rs1129055 and rs17281995) in cancer fail to provide compelling
      evidence. The aim of this study was to investigate the role of common
      polymorphisms in the risk of cancer by meta-analysis. METHODS: By using the
      search terms Cluster of Differentiation 86/CD86/B7
      2/polymorphism/polymorphisms/cancer, we searched PubMed, Embase, CNKI, and
      Wanfang and identified four studies for rs1129055 (2137 subjects) and rs17281995
      (2856 subjects) respectively. Cancer risk was estimated by odds ratio (OR) and
      95% confidence interval (95% CI). MAJOR FINDINGS: Overall, we observed
      significant reduced risk of cancer in relation to rs1129055. Compared with the
      individuals with AA genotype, the individuals with GG genotype appeared to have
      62% decreased risk to develop cancer (GG versus AA: OR, 0.62; 95% CI, 0.49-0.79;
      P(het)., 0.996). Similar effects were indicated in the G versus A allele model
      and the GG versus GA+AA genetic model (OR, 0.83; 95% CI, 0.74-0.93; P(het).,
      0.987; OR, 0.63; 95% CI, 0.50-0.79; P(het)., 0.973). In addition, we found
      genotypes of rs17281995 had a major effect on overall cancer risk (CC versus GG:
      OR, 2.38; 95% CI, 1.43-3.95; P(het)., 0.433; C versus G: OR, 1.23; 95% CI, 1.06
      1.43; P(het)., 0.521; CC versus GC+GG: OR, 2.38; 95% CI, 1.45-3.93; P(het).,
      0.443). The association was also observed in Caucasians and colorectal cancer. No
      obvious publication bias was detected in this meta-analysis. CONCLUSIONS: These
      data reveal that rs1129055 may have protective effects on cancer risk in Asians
      and that rs17281995 is likely to contribute to risk of cancer, particularly
      colorectal cancer in Caucasians.

PMID- 25369325
TI  - Lung cancer screening.
AB  - The United States Preventive Services Task Force recommends lung cancer screening
      with low-dose computed tomography (LDCT) in adults of age 55 to 80 years who have
      a 30 pack-year smoking history and are currently smoking or have quit within the
      past 15 years. This recommendation is largely based on the findings of the
      National Lung Screening Trial. Both policy-level and clinical decision-making
      about LDCT screening must consider the potential benefits of screening (reduced
      mortality from lung cancer) and possible harms. Effective screening requires an
      appreciation that screening should be limited to individuals at high risk of
      death from lung cancer, and that the risk of harm related to false positive
      findings, overdiagnosis, and unnecessary invasive testing is real. A
      comprehensive understanding of these aspects of screening will inform appropriate
      implementation, with the objective that an evidence-based and systematic approach
      to screening will help to reduce the enormous mortality burden of lung cancer. 

PMID- 25369326
TI  - Full-scale validation of a model of algal productivity.
AB  - While modeling algal productivity outdoors is crucial to assess the economic and
      environmental performance of full-scale cultivation, most of the models hitherto
      developed for this purpose have not been validated under fully relevant
      conditions, especially with regard to temperature variations. The objective of
      this study was to independently validate a model of algal biomass productivity
      accounting for both light and temperature and constructed using parameters
      experimentally derived using short-term indoor experiments. To do this, the
      accuracy of a model developed for Chlorella vulgaris was assessed against data
      collected from photobioreactors operated outdoor (New Zealand) over different
      seasons, years, and operating conditions (temperature-control/no temperature
      control, batch, and fed-batch regimes). The model accurately predicted
      experimental productivities under all conditions tested, yielding an overall
      accuracy of +/-8.4% over 148 days of cultivation. For the purpose of assessing
      the feasibility of full-scale algal cultivation, the use of the productivity
      model was therefore shown to markedly reduce uncertainty in cost of biofuel
      production while also eliminating uncertainties in water demand, a critical
      element of environmental impact assessments. Simulations at five climatic
      locations demonstrated that temperature-control in outdoor photobioreactors would
      require tremendous amounts of energy without considerable increase of algal
      biomass. Prior assessments neglecting the impact of temperature variations on
      algal productivity in photobioreactors may therefore be erroneous.

PMID- 25369327
TI  - Criteria for viability assessment of discarded human donor livers during ex vivo
      normothermic machine perfusion.
AB  - Although normothermic machine perfusion of donor livers may allow assessment of
      graft viability prior to transplantation, there are currently no data on what
      would be a good parameter of graft viability. To determine whether bile
      production is a suitable biomarker that can be used to discriminate viable from
      non-viable livers we have studied functional performance as well as biochemical
      and histological evidence of hepatobiliary injury during ex vivo normothermic
      machine perfusion of human donor livers. After a median duration of cold storage
      of 6.5 h, twelve extended criteria human donor livers that were declined for
      transplantation were ex vivo perfused for 6 h at 37  degrees C with an oxygenated
      solution based on red blood cells and plasma, using pressure controlled pulsatile
      perfusion of the hepatic artery and continuous portal perfusion. During
      perfusion, two patterns of bile flow were identified: (1) steadily increasing
      bile production, resulting in a cumulative output of >= 30 g after 6 h (high bile
      output group), and (2) a cumulative bile production <20 g in 6 h (low bile output
      group). Concentrations of transaminases and potassium in the perfusion fluid were
      significantly higher in the low bile output group, compared to the high bile
      output group. Biliary concentrations of bilirubin and bicarbonate were
      respectively 4 times and 2 times higher in the high bile output group. Livers in
      the low bile output group displayed more signs of hepatic necrosis and venous
      congestion, compared to the high bile output group. In conclusion, bile
      production could be an easily assessable biomarker of hepatic viability during ex
      vivo machine perfusion of human donor livers. It could potentially be used to
      identify extended criteria livers that are suitable for transplantation. These ex
      vivo findings need to be confirmed in a transplant experiment or a clinical
      trial.

PMID- 25369328
TI  - Characterization of the CD14++CD16+ monocyte population in human bone marrow.
AB  - Numerous studies have divided blood monocytes according to their expression of
      the surface markers CD14 and CD16 into following subsets: classical CD14(++)CD16(
      ), intermediate CD14(++)CD16(+) and nonclassical CD14(+)CD16(++) monocytes. These
      subsets differ in phenotype and function and are further correlated to
      cardiovascular disease, inflammation and cancer. However, the CD14/CD16 nature of
      resident monocytes in human bone marrow remains largely unknown. In the present
      study, we identified a major population of CD14(++)CD16(+) monocytes by using
      cryopreserved bone marrow mononuclear cells from healthy donors. These cells
      express essential monocyte-related antigens and chemokine receptors such as
      CD11a, CD18, CD44, HLA-DR, Ccr2, Ccr5, Cx3cr1, Cxcr2 and Cxcr4. Notably, the
      expression of Ccr2 was inducible during culture. Furthermore, sorted
      CD14(++)CD16(+) bone marrow cells show typical macrophage morphology, phagocytic
      activity, angiogenic features and generation of intracellular oxygen species.
      Side-by-side comparison of the chemokine receptor profile with unpaired blood
      samples also demonstrated that these rather premature medullar monocytes mainly
      match the phenotype of intermediate and partially of (non)classical monocytes.
      Together, human monocytes obviously acquire their definitive CD14/CD16 signature
      in the bloodstream and the medullar monocytes probably transform into
      CD14(++)CD16- and CD14(+)CD16(++) subsets which appear enriched in the periphery.

PMID- 25369329
TI  - Itch is required for lateral line development in zebrafish.
AB  - The zebrafish posterior lateral line is formed during early development by the
      deposition of neuromasts from a migrating primordium. The molecular mechanisms
      regulating the regional organization and migration of the primordium involve
      interactions between Fgf and Wnt/beta-catenin signaling and the establishment of
      specific cxcr4b and cxcr7b cytokine receptor expression domains. Itch has been
      identified as a regulator in several different signaling pathways, including Wnt
      and Cxcr4 signaling. We identified two homologous itch genes in zebrafish, itcha
      and itchb, with generalized expression patterns. By reducing itchb expression in
      particular upon morpholino knockdown, we demonstrated the importance of Itch in
      regulating lateral line development by perturbing the patterns of cxcr4b and
      cxcr7b expression. Itch knockdown results in a failure to down-regulate Wnt
      signaling and overexpression of cxcr4b in the primordium, slowing migration of
      the posterior lateral line primordium and resulting in abnormal development of
      the lateral line.

PMID- 25369330
TI  - NSFC health research funding and burden of disease in China.
AB  - BACKGROUND: Allocation of health research funds among diseases has never been
      evaluated in China. This study aimed to examine the relationship between disease
      specific funding levels of National Nature Science Foundation of China (NSFC),
      the main governmental resource for health research in China, and burden of
      disease. METHODS: Funding magnitudes for 53 diseases or conditions were obtained
      from the website of NSFC. Measures of disease burden, mortality, years of life
      lost (YLLs) and disability-adjusted life years (DALYs), were derived from the
      Global Burden of Disease Study 2010. The relationship between NSFC funding and
      disease burden was analyzed with univariate linear regression. For each measure
      associated with funding, regression-derived estimates were used to calculate the
      expected funds for each disease. The actual and expected funds were then
      compared. We also evaluated the impacts of changes of disease burden metrics
      since 1990, and differences from the world averages on NSFC funding. RESULTS:
      NSFC health research funding was associated with disease burden measured in
      mortality (R = 0.33, P = 0.02), YLLs (R = 0.39, P = 0.004), and DALYs (R  = 0.40,
      P = 0.003). But none of the changes of mortality (R = 0.22, P = 0.12), YLLs (R = 
      -0.04, P = 0.79) and DALYs (R =  -0.003, P = 0.98) since 1990 was associated with
      the funding magnitudes. None of the differences of mortality (R =  -0.11, P =
      0.45), YLLs (R =  -0.11, P = 0.43) and DALYs (R =  -0.12, P = 0.38) from that of
      the concurrent world averages were associated with the funding magnitudes.
      Measured by DALY, stroke and COPD received the least funding compared to
      expected; while leukemia and diabetes received the most funding compared to
      expected. CONCLUSION: Although NSFC funding were roughly associated with disease
      burden as measured in mortality, YLLs and DALYs. Some major diseases such as
      stroke were underfunded; while others such as leukaemia were overfunded. Change
      of disease burden during the last 20 years and country-specialized disease burden
      were not reflected in current allocation of NSFC funds.

PMID- 25369331
TI  - Lifestyle factors associated with type 2 diabetes and use of different glucose
      lowering drugs: cross-sectional study.
AB  - AIMS: To examine the lifestyle profile among persons with and without Type 2
      diabetes mellitus (DM) and among users of different glucose-lowering drugs.
      METHODS: We used questionnaire data from a Danish health survey and identified
      presence of Type 2 DM and use of medications through medical databases. We
      calculated age- and gender-standardized prevalence ratios (PRs) of lifestyle
      factors according to Type 2 DM and different glucose-lowering drugs. RESULTS: Of
      21,637 survey participants aged 25-79 years, 680 (3%) had Type 2 DM (median age
      63 years) with a median diabetes duration of 5 years. Participants with Type 2 DM
      had a substantially higher prevalence of obesity (36% vs. 13%, PR: 3.1, 95%
      confidence interval (CI): 2.8-3.6), yet more reported to eat a very healthy diet
      (25% vs. 21%, PR: 1.2, 95% CI: 1.0-1.4) and to exercise regularly (67% vs. 53%,
      PR: 1.3, 95% CI: 1.2-1.4). Also, fewer were current smokers or had high alcohol
      intake. When compared with metformin users, obesity was substantially less
      prevalent in users of sulfonylurea (PR: 0.5, 95% CI: 0.4-0-8), and insulin and
      analogues (PR: 0.4, 95% CI: 0.3-0.7). Tobacco smoking was more prevalent in
      sulfonylurea users (PR: 1.4, 95% CI: 0.9-2.1) compared with metformin users. We
      found no material differences in physical exercise, diet or alcohol intake
      according to type of glucose-lowering drug. CONCLUSIONS: Type 2 DM patients are
      substantially more obese than other individuals, but otherwise report to have a
      healthier lifestyle. Metformin use is strongly associated with obesity, whereas
      sulfonylurea use tends to be associated with tobacco smoking.

PMID- 25369332
TI  - miR-27 negatively regulates pluripotency-associated genes in human embryonal
      carcinoma cells.
AB  - Human embryonic stem cells and human embryonal carcinoma cells have been studied
      extensively with respect to the transcription factors (OCT4, SOX2 and NANOG),
      epigenetic modulators and associated signalling pathways that either promote self
      renewal or induce differentiation in these cells. The ACTIVIN/NODAL axis
      (SMAD2/3) of the TGFbeta signalling pathway coupled with FGF signalling maintains
      self-renewal in these cells, whilst the BMP (SMAD1,5,8) axis promotes
      differentiation. Here we show that miR-27, a somatic-enriched miRNA, is activated
      upon RNAi-mediated suppression of OCT4 function in human embryonic stem cells. We
      further demonstrate that miR-27 negatively regulates the expression of the
      pluripotency-associated ACTIVIN/NODAL axis (SMAD2/3) of the TGFbeta signalling
      pathway by targeting ACVR2A, TGFbetaR1 and SMAD2. Additionally, we have
      identified a number of pluripotency-associated genes such as NANOG, LIN28, POLR3G
      and NR5A2 as novel miR-27 targets. Transcriptome analysis revealed that miR-27
      over-expression in human embryonal carcinoma cells leads indeed to a significant
      up-regulation of genes involved in developmental pathways such as TGFbeta- and
      WNT-signalling. 

PMID- 25369334
TI  - Frequent chromatin rearrangements in myelodysplastic syndromes--what stands
      behind?
AB  - Myelodysplastic syndromes (MDS) represent a clinically and genetically
      heterogeneous group of clonal haematopoietic diseases characterized by a short
      survival and high rate of transformation to acute myeloid leukaemia (AML). In
      spite of this variability, MDS is associated with typical recurrent non-random
      cytogenetic defects. Chromosomal abnormalities are detected in the malignant bone
      marrow cells of approximately 40-80 % of patients with primary or secondary MDS.
      The most frequent chromosomal rearrangements involve chromosomes 5, 7 and 8. MDS
      often shows presence of unbalanced chromosomal changes, especially large
      deletions [del(5), del(7q), del(12p), del(18q), del(20q)] or losses of whole
      chromosomes (7 and Y). The most typical cytogenetic abnormality is a partial or
      complete deletion of 5q- that occurs in roughly 30 % of all MDS cases either as
      the sole abnormality or in combination with other aberrations as a part of
      frequently complex karyotypes. The mechanisms responsible for the formation of
      MDS-associated recurrent translocations and complex karyotypes are unknown. Since
      some of the mentioned aberrations are characteristic for several haematological
      malignancies, more general cellular conditions could be expected to play a role.
      In this article, we introduce the most common rearrangements linked to MDS and
      discuss the potential role of the non-random higher-order chromatin structure in
      their formation. A contribution of the chromothripsis - a catastrophic event
      discovered only recently - is considered to explain how complex karyotypes may
      occur (during a single event).

PMID- 25369335
TI  - Novel insights into the electrochemical detection of nitric oxide in biological
      systems.
AB  - In recent years, microsensor technologies have made a rapid expansion into
      different fields of physical sciences, engineering, and biomedicine. For analyses
      of various biomolecules, novel sensors and detection platforms in the
      electrochemical field have been reported recently. The most important
      applications based on microelectromechanical systems dramatically reduce the need
      of manipulation steps with samples, while improving data quality and quantitative
      capabilities. This is also the case of a special class of electrochemical sensors
      that allow direct, real-time and non-invasive measurements of nitric oxide, whose
      determination is crucial for the purposes of basic research, as well as of
      preclinical and clinical studies. Therefore, this minireview will focus on the
      description of recent discoveries in the electrochemical determination of nitric
      oxide, released in different in vitro systems. 

PMID- 25369336
TI  - Structural basis of polycomb bodies.
AB  - The spatial organization of the cell nucleus into separated domains with a
      specific macromolecular composition seems to be the fundamental principle that
      regulates its functioning. Because of the importance of regulation at the nuclear
      level, the cell nucleus and its domains have been intensively studied. This
      review is focused on the nuclear domain termed the Polycomb (PcG) body. We
      summarize and discuss data reported in the literature on different components of
      the PcG body that could form its structural basis. First, we describe the protein
      nature of the PcG body and the gene silencing factory model. Second, we review
      the target genes of Polycomb-mediated silencing and discuss their essentiality
      for the structural nature of the PcG body. In this respect, two different
      schematic models are presented. Third, we mention new data on the importance of
      RNAs, insulator elements and insulator proteins for the structure of PcG bodies.
      With this review, we hope to illustrate the importance of understanding the
      nature of the PcG subcompartment. The structural basis of a subcompartment
      directly reflects its status in the cell nucleus and the mechanism of its
      function. 

PMID- 25369337
TI  - Recent approaches in tooth engineering research.
AB  - Tooth absence and defects caused by various reasons are frequent events in
      humans. They are not life threatening but may bring about social consequences.
      Recent dentistry provides solutions in the form of prosthetics or dental
      implants; however, several complications and distinct limitations favour
      bioengineering of dental and periodontal structures. At least two types of cells
      (epithelial and mesenchymal) have to be recombined to produce a new functional
      tooth. Moreover, the tooth must be vascularized, innervated and properly anchored
      in the bone. To study these issues, different approaches have been established in
      both basic and applied research. In this review, recent strategies and techniques
      of tooth engineering are comprehensively summarized and discussed, particularly
      regarding manipulation using stem cells. 

PMID- 25369333
TI  - CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV
      infected individuals independently of disease progression.
AB  - Mucosal-associated invariant T (MAIT) cells are characterized by the combined
      expression of the semi-invariant T cell receptor (TCR) Valpha7.2, the lectin
      receptor CD161, as well as IL-18R, and play an important role in antibacterial
      host defense of the gut. The current study characterized CD161(+) MAIT and CD161
      TCRValpha7.2(+) T cell subsets within a large cohort of HIV patients with
      emphasis on patients with slow disease progression and elite controllers.
      Mononuclear cells from blood and lymph node samples as well as plasma from 63
      patients and 26 healthy donors were analyzed by multicolor flow cytometry and
      ELISA for IL-18, sCD14 and sCD163. Additionally, MAIT cells were analyzed after
      in vitro stimulation with different cytokines and/or fixed E.coli. Reduced
      numbers of CD161(+) MAIT cells during HIV infection were detectable in the blood
      and lymph nodes of all patient groups, including elite controllers. CD161+ MAIT
      cell numbers did not recover even after successful antiretroviral treatment. The
      loss of CD161(+) MAIT cells was correlated with higher levels of MAIT cell
      activation; an increased frequency of the CD161-TCRValpha7.2(+)T cell subset in
      HIV infection was observed. In vitro stimulation of MAIT cells with IL-18 and IL
      12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the
      MAIT cell frequency defined by CD161, IL-18R and CCR6. In summary, the
      irreversible reduction of the CD161(+) MAIT cell subset seems to be an early
      event in HIV infection that is independent of later stages of the disease. This
      loss appears to be at least partially due to the distinctive vulnerability of
      MAIT cells to the pronounced stimulation by microbial products and cytokines
      during HIV-infection.

PMID- 25369338
TI  - Properties of neural crest-like cells differentiated from human embryonic stem
      cells.
AB  - Neural crest cells (NCCs) derive early in vertebrate ontogenesis from neural tube
      as a population of migratory cells with exquisite differentiation potential.
      Abnormalities in NCC behaviour are cause of debilitating diseases including
      cancers and a spectrum of neurocristopathies. Thanks to their multilineage
      differentiation capacity NCCs offer a cell source for regenerative medicine. Both
      these aspects make NCC biology an important issue to study, which can currently
      be addressed using methodologies based on pluripotent stem cells. Here we
      contributed to understanding the biology of human NCCs by refining the protocol
      for differentiation/propagation of NCClike cells from human embryonic stem cells
      and by characterizing the molecular and functional phenotype of such cells. Most
      importantly, we improved formulation of media for NCC culture, we found that poly
      L-ornithine combined with fibronectin provide good support for NCC growth, we
      unravelled the tendency of cultured NCCs to maintain heterogeneity of CD271
      expression, and we showed that NCCs derived here possess the capacity to react to
      BMP4 signals by dramatically up-regulating MSX1, which is linked to
      odontogenesis. 

PMID- 25369339
TI  - The effects of chloroquine and hydroxychloroquine on nitric oxide production in
      RAW 264.7 and bone marrow-derived macrophages.
AB  - Chloroquine, an antimalarial drug, can also be used in the regulation of the
      immune system, e.g. it is used in the treatment of autoimmune diseases. In this
      study we investigated the effects of chloroquine and its hydroxy-derivative on
      nitric oxide (NO) production in two different cell types: (i) immortalized mouse
      macrophage cell line RAW 264.7 and (ii) mouse bone marrow-derived macrophages
      (BMDM). The cells were treated with different concentrations (1-100 MUM) of
      chloroquine or hydroxychloroquine and stimulated with lipopolysaccharide for 24 h
      to induce NO production. Measurement of nitrites by the Griess reaction was used
      to evaluate the production of NO. Expression of inducible NO synthase was
      evaluated with Western blot and ATPcytotoxicity test was used to measure the
      viability of the cells. Our results showed that both chloroquine and its hydroxy
      derivative inhibited NO production in both cell types. However, based on the
      results of LD50 these inhibitory effects of both derivatives were due to their
      cytotoxicity. The LD50 values for chloroquine were 24.77 MUM (RAW 264.7) and
      24.86 MUM (BMDM), the LD50 for hydroxychloroquine were 13.28 MUM (RAW 264.7) and
      13.98 MUM (BMDM). In conclusion, hydroxychloroquine was more cytotoxic than its
      parent molecule. Comparing the two cell types tested, our data suggest that there
      are no differences in cytotoxicity of chloroquine or hydroxychloroquine for
      primary cells (BMDM) or immortalized cell line (RAW 264.7).

PMID- 25369340
TI  - Visualizing stable features in live cell nucleus for evaluation of the cell
      global motion compensation.
AB  - The compensation of cell motion is an important step in single-particle tracking
      analysis of live cells. This step is required in most of the cases, since the
      movement of subcellular foci is superimposed by the movement and deformation of
      the cell, while only the local motion of the foci is important to be analysed.
      The cell motion and deformation compensation is usually performed by means of
      image registration. There are a number of approaches with different models and
      properties presented in the literature that perform cell image registration.
      However, the evaluation of the registration approach quality on real data is a
      tricky problem due to the fact that some stable features in the images with a
      priori no local motion are needed. In this paper we propose a methodology for
      creating live cell nuclei image sequences with stable features imposed. The
      features are defined using the regions of fluorescence bleaching invoked by the
      UV laser. Data with different deformations are acquired and can be used for
      evaluation of the cell image registration methods. Along with that, we describe
      an image analysis technique and a metric that can characterize the quality of the
      method quantitatively. The proposed methodology allows building a ground truth
      dataset for testing and thoroughly evaluating cell image registration methods. 

PMID- 25369341
TI  - Utilization of an automated pipetting system in the cell line-based screening of
      the activity of a DNA-damaging anti-tumour drug.
AB  - The principles of large screening strategies, which are developed by industrial
      companies, have been recently adopted by researchers in the fields of molecular
      biology and oncology as invaluable tools for translational medicine. The
      declining costs of laboratory robotic machines have allowed high-throughput
      screening to become more available to academic centres with limited resources.
      Here, we describe how a robotic conventional liquid handling system could be used
      on a daily basis in laboratories to obtain consistent and reproducible results.
      Our approach allowed us to quickly screen a panel of more than 20 tumorigenic and
      non-tumorigenic cell lines for their responses to hydroxyurea, which is a DNA
      damaging anticancer therapeutic drug. The format of 384-well microplates was used
      for manual cell seeding, and the effect of hydroxyurea was screened at multiple
      concentrations. The fluorescence-based CyQuant assay was employed as the readout
      method to analyse the cellular DNA content. The effectiveness of our approach was
      demonstrated in the experimental results.

PMID- 25369342
TI  - Phthalates deregulate cell proliferation, but not neuroendocrine
      transdifferentiation, in human LNCaP prostate cancer cell model.
AB  - Phthalate esters are ubiquitous environmental pollutants widely used as
      plasticizers, which have been shown to interfere with both endocrine regulation
      and development of reproductive organs. In the present study, we examined the
      impact of diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) on the
      proliferation of androgen-sensitive human prostate carcinoma LNCaP cells and
      related events. The results showed that both compounds were able to inhibit cell
      cycle progression in a dose-dependent manner. However, only DEHP was found to
      weakly reduce androgen receptor (AR) protein levels after long-term exposure,
      while only DBP partially inhibited expression of the prostate-specific antigen
      (KLK3) gene, a model AR transcriptional target. This indicated that inhibition of
      cell proliferation was likely independent of any AR modulations. Both phthalates
      induced suppression of cell proliferation, but none of them affected the levels
      of markers associated with neuroendocrine transdifferentiation (NED) in LNCaP
      cells. Taken together, the presented data indicate that phthalates may exert long
      term negative effects on the proliferation of prostate epithelial cells derived
      from the carcinoma model, which are, nevertheless, largely independent of the
      modulation of AR expression/activity, and which do not alter further processes
      associated with NED.

PMID- 25369343
TI  - Three-dimensional reconstruction of the S885A mutant of human mitochondrial Lon
      protease.
AB  - The Lon protein is a protease belonging to the superfamily of ATPases associated
      with diverse cellular activities (AAA+). Its main function is the control of
      protein quality and the maintenance of proteostasis by degradation of misfolded
      and damaged proteins, which occur in response to numerous stress conditions. It
      also participates in the regulation of levels of transcription factors that
      control pathogenesis, development and stress response. We focus our interest on
      the structure of human mitochondrial Lon (hLon) protease, whose altered
      expression levels are linked to some severe diseases such as epilepsy, myopathy,
      or lateral sclerosis. We present the first 3D structure of the ADP-bound human
      Lon S885A mutant obtained by electron microscopy as a result of preliminary
      negative staining studies. S885A appears as a hexameric ring of 120 A diameter
      having 90 A in height. Its resolution was estimated at 19 A by the FSC = 0.5
      criterion. This model is a primary step towards the understanding of the
      mechanism of action of the Lon protease and its involvement in the pathogenesis
      development. 

PMID- 25369344
TI  - Sub-volume averaging of repetitive structural features in angularly filtered
      electron tomographic reconstructions.
AB  - Electron tomographic reconstructions suffer from a number of artefacts arising
      from effects accompanying the processes of acquisition of a set of tilted
      projections of the specimen in a transmission electron microscope and from its
      subsequent computational handling. The most pronounced artefacts usually come
      from imprecise projection alignment, distortion of specimens during tomogram
      acquisition and from the presence of a region of missing data in the Fourier
      space, the "missing wedge". The ray artefacts caused by the presence of the
      missing wedge can be attenuated by the angular image filter, which attenuates the
      transition between the data and the missing wedge regions. In this work, we
      present an analysis of the influence of angular filtering on the resolution of
      averaged repetitive structural motives extracted from three-dimensional
      reconstructions of tomograms acquired in the single-axis tilting geometry. 

PMID- 25369345
TI  - Mysterious role of H3K56ac in embryonic stem cells.
AB  - Posttranslational modifications of histones belong to epigenetic mechanisms that
      regulate gene expression by chromatin structure changes. Generally, histone
      acetylation reduces its positive charge and consequently weakens the stability of
      the nucleosome. Acetylation of lysine 56 on histone H3 is implicated in the
      processes associated with loosened chromatin structure. H3K56ac is a mark for
      histones with high nucleosome turnover in the nuclear processes such as gene
      transcription, DNA replication and reparation in yeasts. During evolution, the
      main H3K56ac regulatory pathway was lost and the level of H3K56ac remained very
      low in mammalian cells. Moreover, the function of this modification still remains
      unclear. In this minireview, we summarize the recent knowledge of the ambiguous
      role of H3K56ac in mammalian embryonic stem cells. 

PMID- 25369346
TI  - Advanced microscopy techniques used for comparison of UVA- and gamma-irradiation
      induced DNA damage in the cell nucleus and nucleolus.
AB  - Every day, genomes are affected by genotoxic factors that create multiple DNA
      lesions. Several DNA repair systems have evolved to counteract the deleterious
      effects of DNA damage. These systems include a set of DNA repair mechanisms,
      damage tolerance processes, and activation of cell-cycle checkpoints. This study
      describes selected confocal microscopy techniques that investigate DNA damage
      related nuclear events after UVA- and gamma-irradiation and compare the DNA
      damage response (DDR) induced by the two experimental approaches. In both cases,
      we observed induction of the nucleotide excision repair (NER) pathway and
      formation of localized double-strand breaks (DSBs). This was confirmed by
      analysis of cyclobutane pyrimidine dimers (CPDs) in the DNA lesions and by
      increased levels of gammaH2AX and 53BP1 proteins in the irradiated genome. DNA
      damage by UVA-lasers was potentiated by either BrdU or Hoechst 33342 pre
      sensitization and compared to non-photosensitized cells. DSBs were also induced
      without BrdU or Hoechst 33342 pre-treatment. Interestingly, no cyclobutane
      pyrimidine dimers (CPDs) were detected after 405 nm UVA laser micro-irradiation
      in non-photosensitized cells. The effects of UVA and gamma-irradiation were also
      studied by silver staining of nucleolar organizer regions (AgNORs). This
      experimental approach revealed changes in the morphology of nucleoli after genome
      injury. Additionally, to precisely characterize DDR in locally induced DNA
      lesions, we analysed the kinetics of the 53BP1 protein involved in DDR by
      fluorescence recovery after photobleaching (FRAP). 

PMID- 25369347
TI  - Generation of human induced pluripotent stem cells using genome integrating or
      non-integrating methods.
AB  - Preclinical studies have demonstrated the promising potential of human induced
      pluripotent stem cells (hiPSCs) for clinical application. To fulfil this goal,
      efficient and safe methods to generate them must be established. Various
      reprogramming techniques were presented during seven years of hiPSCs research.
      Genome non-integrating and completely xeno-free protocols from the first biopsy
      to stable hiPSC clones are highly preferable in terms of future clinical
      application. In this short communication, we summarize the reprogramming
      experiments performed in our laboratories. We successfully generated hiPSCs using
      STEMCCA lentivirus, Sendai virus or episomal vectors. Human neonatal fibroblasts
      and CD34(+) blood progenitors were used as cell sources and were maintained
      either on mouse embryonic feeder cells or in feeder-free conditions. The
      reprogramming efficiency was comparable for all three methods and both cell
      types, while the best results were obtained in feeder-free conditions. 

PMID- 25369348
TI  - Haematopoietic developmental potential of human pluripotent stem cell lines.
AB  - The generation of haematopoietic progenitors from human pluripotent stem cells
      (hPSCs) presents great promise for cell-replacement therapies. However, current
      protocols for haematopoietic differentiation of hPSCs suffer from low efficiency
      and functional defects in the derived cells. The technology is also limited by
      variable ability of hPSC lines to generate blood cells in vitro. To address this
      issue, methodologies for haematopoietic differentiation in feeder-free conditions
      were applied to available human embryonic stem cell (hESC) and human induced
      pluripotent stem cell (hiPSC) lines in this study. It was found that these cell
      lines did not generate haematopoietic progenitors to such an extent as did H1 and
      H9 hESC lines that were used for this purpose in the vast majority of relevant
      studies. These results suggest that for clinical application of blood cells
      derived from hPSCs, possibly from autologous hiPSCs, it is necessary to overcome
      the variability in the haematopoietic developmental potential of individual hPSC
      lines. 

PMID- 25369349
TI  - Composition-structure-function diagrams of Ti-Ni-Au thin film shape memory
      alloys.
AB  - Ti-Ni-Au thin film materials libraries were prepared from multilayer precursors
      by combinatorial sputtering. The materials libraries were annealed at 500, 600,
      and 700  degrees C for 1 h and then characterized by high-throughput methods to
      investigate the relations between composition, structure and functional
      properties. The identified relations were visualized in functional phase
      diagrams. The goal is to identify composition regions that are suitable as high
      temperature shape memory alloys. Phase transforming compositions were identified
      by electrical resistance measured during thermal cycles in the range of -20 and
      250  degrees C. Three phase transformation paths were confirmed: (1) B2-R, (2) B2
      R-B19', and (3) B2-B19. For the materials library annealed at 500  degrees C only
      the B2-R transformation was observed. For the materials libraries annealed at 600
      and 700  degrees C, all transformation paths were observed. High transformation
      temperatures (M(s) ~ 100  degrees C) were only obtained by annealing at 600 or
      700  degrees C, and with compositions of Ti ~ 50 at. % and Au > 20 at. %. This is
      the composition range that undergoes B2-B19 transformation. The phase
      transformation behaviors were explained according to the compositional and
      annealing temperature dependence of phase/structure formation, as revealed by X
      ray diffraction analysis of the materials libraries.

PMID- 25369350
TI  - Hanoi tower-like multilayered ultrathin palladium nanosheets.
AB  - This paper describes the synthesis, formation mechanism, and mechanical property
      of multilayered ultrathin Pd nanosheets. An anisotropic, Hanoi Tower-like
      assembly of Pd nanosheets was identified by transmission electron microscopy and
      atomic force microscopy (AFM). These nanosheets may contain ultrathin Pd layers,
      down to single unit cell thickness. Selected area electron diffraction and
      scanning transmission electron microscopy data show the interconnected atomically
      thick layers stacking vertically with rotational mismatches, resulting in unique
      diffractions and Moire patterns. Density functional theory (DFT) calculation with
      van der Waals correction (DFT+vdW) shows the adsorption of Pd4(CO)4(OAc)4 on
      Pd(110) surface (Ead = -5.68 eV) is much stronger than that on Pd(100) (Ead = 
      4.72 eV) or on Pd(111) (Ead = -3.80 eV). The adsorption strength of this Pd
      complex is significantly stronger than that of CO on the same Pd surfaces. The
      DFT+vdW calculation results suggest a new mechanism for the observed anisotropic
      growth of nanosheets with unusually high aspect ratio, in which the competitive
      adsorptions between Pd4(CO)4(OAc)4 complex and CO on various surfaces result in a
      favored growth along the ?110? directions and inhibition along ?111? directions.
      The mechanical property of these multilayered Pd nanosheets was studied using AFM
      and nanoindentation techniques, which indicate multilayered nanosheets show more
      plastic deformation than the bulk in response to an applied force. 

PMID- 25369351
TI  - Vape and vitriol in public health.

PMID- 25369352
TI  - The effectiveness of regionalization of perinatal care services--a systematic
      review.
AB  - BACKGROUND: Several reports recommend the implementation of perinatal
      regionalization for improvements in maternal and neonatal outcomes, while
      research evidence on the effectiveness of perinatal regionalization has been
      limited. The interventional studies have been assessed for robust evidence on the
      effectiveness of perinatal regionalization on improving maternal and neonatal
      health outcomes. METHODS: Bibliographic databases of Medline, EMbase, EconLit,
      HMIC have been searched using sensitive search terms for interventional studies
      that reported important patient or process outcomes. At least two authors
      assessed eligibility for inclusion and the risk of biases and extracted data from
      the included studies. As meta-analysis was not possible, a narrative analysis as
      well as a 'vote-counting' analysis has been conducted for important outcomes.
      RESULTS: After initial screenings 53 full text papers were retrieved. Eight
      studies were included in the review from the USA, Canada and France. Studies
      varied in their designs, and in the specifications of the intervention and
      setting. Only three interrupted time series studies had a low risk of bias, of
      which only one study reported significant reductions in neonatal and infant
      mortality. Studies of higher risk of bias were more likely to report improvements
      in outcomes. CONCLUSIONS: Implementing perinatal regionalization programs is
      correlated with improvements in perinatal outcomes, but it is not possible to
      establish a causal link. Despite several high profile policy statements, evidence
      of effect is weak. It is necessary to assess the effectiveness of perinatal
      regionalization using robust research designs in a more diverse range of
      countries.

PMID- 25369353
TI  - Urbanization and non-communicable disease in Southeast Asia: a review of current
      evidence.
AB  - OBJECTIVE: Non-communicable diseases (NCDs) have been highlighted as a major
      public health issue in the Southeast (SE) Asian region. One of the major socio
      environmental factors that are considered to be associated with such a rise in
      NCDs is urbanization. Urbanization is associated with behavioural changes such as
      eating an unhealthy diet, and a decrease in physical activities, which may result
      in associated obesity. The SE Asian region also has a substantive burden of
      infectious disease such as HIV and malaria, which may modify associations between
      urbanization and development of NCDs. STUDY DESIGN: A systematic review was
      conducted until April 2013. METHODS: Using four databases: EMBASE, PubMed,
      GlobalHealth and DigitalJournal, the systematic review pools existing evidence on
      urban-rural gradients in NCD prevalence/incidence. RESULTS: The study found that
      in SE Asia, urban exposure was positively associated with coronary heart disease,
      diabetes and respiratory diseases in children. Urban exposure was negatively
      associated with rheumatic heart diseases. The stages of economic development may
      also modify the association between urbanization and NCDs such as diabetes.
      CONCLUSION: There was pronounced heterogeneity between associations. It is
      recommended that future studies examine the major constituents of NCDs separately
      and also focus on the interplay between lifestyle and infectious risk factors for
      NCDs. Prospective studies are needed to understand the diverse causal pathways
      between urbanization and NCDs in SE Asia.

PMID- 25369354
TI  - Prioritising public health guidance topics in the National Institute for Health
      and Care Excellence using the Analytic Hierarchy Process.
AB  - OBJECTIVES: The Centre for Public Health (CPH), at the United Kingdom's National
      Institute for Health and Care Excellence (NICE) is responsible for producing
      national guidance relating to the promotion of good health and the prevention and
      treatment of disease. Given the challenges of developing guidance in this area,
      choosing the most appropriate topics for further study is of fundamental
      importance. This paper explores the current prioritisation process and describes
      how the Analytic Hierarchy Process (AHP), a multi criteria decision analysis
      (MCDA) technique, might be used to do so. STUDY DESIGN: A proposed approach is
      outlined, which was tested in a proof of concept pilot. This consisted of eight
      participants with experience of related NICE committees building scores for each
      topic together in a 'decision conference' setting. METHODS: Criteria were
      identified and subsequently weighted to indicate the relative importance of each.
      Participants then collaboratively estimated the performance of each topic on each
      criterion. RESULTS: Total scores for each topic were calculated, which could be
      ranked and used as the basis for better informed discussion for prioritising
      topics to recommend to the Minister for future guidance. Sensitivity analyses of
      the dataset found it to be robust. CONCLUSIONS: Choosing the right topics for
      guidance at the earliest possible time is of fundamental importance to public
      health guidance, and judgement is likely to play an important part in doing so.
      MCDA techniques offer a potentially useful approach to structuring the problem in
      a rational and transparent way. NICE should consider carefully whether such an
      approach might be worth pursuing in the future.

PMID- 25369355
TI  - The differential impact of the financial crisis on health in Ireland and Greece:
      a quasi-experimental approach.
AB  - OBJECTIVES: Greece and Ireland suffered an economic recession of similar
      magnitude, but whether their health has deteriorated as a result has not yet been
      well established. STUDY DESIGN: Based on five waves (2006-2010) of the European
      Union Statistics of Income and Living Conditions (EU-SILC) survey a (DID)
      approach was implemented that compared trends in self-rated health in Greece and
      Ireland before and after the crisis with trends in a 'control' population
      (Poland) that did not experience a recession and had health trends comparable to
      both countries before the crisis. METHODS: Logistic regression using a (DID)
      approach. RESULTS: A simple examination of trends suggests that there was no
      significant change in health in Greece or Ireland following the onset of the
      financial crisis. However, DID estimates that incorporated a control population
      suggest an increase in the prevalence of poor self-rated health in Greece (OR =
      1.216; CI = 1.11-1.32). Effects were most pronounced for older individuals and
      those living in high-density areas, but effects in Greece were overwhelmingly
      consistent in different population sub-groups. In contrast, DID estimates
      revealed no effect of the financial crisis on the prevalence of poor self-rated
      health in Ireland (OR = 0.97; CI = 0.81-1.16). CONCLUSIONS: DID estimates suggest
      that the financial crisis led to higher prevalence of reporting poor health in
      Greece but not in Ireland. Although the research design does not allow the
      authors to directly assess the role of specific policies, contextual factors
      including policy responses may have contributed to the different effect of the
      crisis on the health of the two countries.

PMID- 25369356
TI  - Evaluation of a programme in population health management for GP trainees.
AB  - OBJECTIVES: There is an increasing focus on improving outcomes for populations.
      General practice has a key role to play in achieving better patient outcomes. A
      programme in population health management was developed for GP trainees in their
      fourth year. The objective was to evaluate this educational intervention for
      impact upon learners, and lessons learned in the delivery of this innovative
      programme. METHODS: The evaluation approach combined qualitative and quantitative
      approaches involving GP trainees, GP trainers, and faculty. RESULTS: Involvement
      in the programme had a positive impact upon trainees' knowledge of population
      health management, developed transferable skills, and encouraged a shift in
      mindset to considering the needs of a practice population. The impact upon
      patients and practices is also described. Lessons learned for enhancing the
      programme are explained. CONCLUSIONS: Encouraging GP trainees to become involved
      with population health has significant benefits for their professional
      development. The Royal College of General Practitioners (RCGP) curriculum should
      consider incorporating population health competencies.

PMID- 25369357
TI  - 'But you can't reverse a hysterectomy!' Perceptions of long acting reversible
      contraception (LARC) among young women aged 16-24 years: a qualitative study.
AB  - OBJECTIVES: Long Acting Reversible Contraception (LARC) methods are highly
      effective in reducing the incidence of unwanted pregnancy. Recent data indicates
      that the rate of abortion in Grampian, North East of Scotland is above the
      Scottish average and LARC uptake among young women low. This study sought to
      explore young women's perceptions of LARC, with the aim of developing a strategy
      to increase LARC uptake. STUDY DESIGN: Qualitative study. METHODS: Sixty five
      women aged 16-24 were randomly recruited to this qualitative study from community
      centres and shopping areas. Recruitment and interviews were conducted in
      friendship pairs, triads or one-to-one basis. Participants were asked about
      current and past contraception use, views of contraception methods including
      LARC; and sources of information about contraception. Data were analysed using
      thematic content analysis. RESULTS: Women interviewed were aware of some of the
      delivery systems used for long acting contraception (intrauterine devices,
      implants and injections) but did not recognise them as 'LARC'. 'Long acting' was
      equated with permanency and the term 'reversible' appeared to have the opposite
      effect to its intention. Intrauterine devices were commonly referred to as
      'coil'. The women often relied on verbal testimonies from those who had
      experienced using LARC, many of which were negative and inaccurate. A lack of in
      depth knowledge about LARC and the opinion that LARC methods were for older women
      were also cited as barriers to use. CONCLUSIONS: This study shows that negative
      testimonies and the belief that LARC are not appropriate for young women may
      discourage LARC uptake.

PMID- 25369358
TI  - Burden of heart disease in Greece: time to act.

PMID- 25369359
TI  - The NHS Constitution values are not always clearly expressed on Trust websites in
      England.

PMID- 25369360
TI  - Targeting mid-life risk factors to reduce late-life dementia.

PMID- 25369361
TI  - Physical activity promotion in 2014--the Tour de France: a local perspective.

PMID- 25369362
TI  - Substituent electronic effects govern direct intramolecular C-N cyclization of N
      (Biphenyl)pyridin-2-amines induced by hypervalent iodine(III) reagents.
AB  - The hypervalent iodine(III) reagent-induced the direct intramolecular C-N
      cyclization of N-(biphenyl)pyridin-2-amines to 6-arylbenzimidazoles and N
      pyridinyl-9H-carbazoles is presented. The substituent electronic effects
      governing the formation of benzimidazoles and carbazoles from the reaction of N
      (biphenyl)pyridin-2-amines with hypervalent iodine(III) reagents is investigated.
      Radical trapping and UV-vis spectroscopic experiments on the detection of the
      cation radical are carried out. Rational mechanisms for these reactions are
      presented. The selective intramolecular C-N and C-O cyclization of N
      (biphenyl)acetamides based on the substituent electronic effects is also
      presented. 

PMID- 25369363
TI  - Act II of the Sunshine Act.
AB  - To coincide with the introduction in the United States of the Sunshine Act,
      Genevieve Pham-Kanter discusses what we need to look for to fight hidden bias and
      deliberate or unconscious corruption. Please see later in the article for the
      Editors' Summary. 

PMID- 25369364
TI  - Triple subconjunctival bevacizumab injection for early corneal recurrent
      pterygium: one-year follow-up.
AB  - PURPOSE: The aim of the study was to evaluate the effect of 3 subconjunctival
      bevacizumab injections in patients with an early corneal pterygium recurrence.
      METHODS: This study was a nonrandomized single center trial. Patients with an
      early corneal pterygium recurrence were selected. All patients received 3
      subconjunctival bevacizumab (2.5 mg/0.1 mL) injections (basal, 2 and 4 weeks) in
      the recurrence area of the pterygium. The corneal and corneal-conjunctival
      neovascularization areas and the corneal opacification area of each pterygium
      were determined using digital slit lamp pictures. RESULTS: Thirty-eight patients
      were enrolled into the study; all patients were injected within 3 months of the
      diagnosed pterygium recurrence. Interestingly, the bevacizumab injections had a
      significant effect (P<0.05) on the reduction of corneal, corneal-conjunctival
      area of neovascularization determined as pixels and on the corneal opacification
      area determined as mm(2) when comparing the basal values, to the values obtained
      after 15 days, 1 month, 3 months, 6 months, and 12 months after injections.
      CONCLUSIONS: The vascularized area in all recurrent pterygia and the corneal
      opacification area with this triple regimen of subconjunctival bevacizumab
      injections were reduced, which remained until the end of the study. These results
      suggest that bevacizumab subconjunctival injections could be useful to treat
      recurrent pterygium.

PMID- 25369365
TI  - A phylogeny-based benchmarking test for orthology inference reveals the
      limitations of function-based validation.
AB  - Accurate orthology prediction is crucial for many applications in the post
      genomic era. The lack of broadly accepted benchmark tests precludes a
      comprehensive analysis of orthology inference. So far, functional annotation
      between orthologs serves as a performance proxy. However, this violates the
      fundamental principle of orthology as an evolutionary definition, while it is
      often not applicable due to limited experimental evidence for most species.
      Therefore, we constructed high quality "gold standard" orthologous groups that
      can serve as a benchmark set for orthology inference in bacterial species.
      Herein, we used this dataset to demonstrate 1) why a manually curated, phylogeny
      based dataset is more appropriate for benchmarking orthology than other popular
      practices and 2) how it guides database design and parameterization through
      careful error quantification. More specifically, we illustrate how function-based
      tests often fail to identify false assignments, misjudging the true performance
      of orthology inference methods. We also examined how our dataset can instruct the
      selection of a "core" species repertoire to improve detection accuracy. We
      conclude that including more genomes at the proper evolutionary distances can
      influence the overall quality of orthology detection. The curated gene families,
      called Reference Orthologous Groups, are publicly available at
      http://eggnog.embl.de/orthobench2. 

PMID- 25369366
TI  - A novel method to evaluate the community built environment using photographs-
      Environmental Profile of a Community Health (EPOCH) photo neighbourhood
      evaluation tool.
AB  - BACKGROUND: Previous research has shown that environments with features that
      encourage walking are associated with increased physical activity. Existing
      methods to assess the built environment using geographical information systems
      (GIS) data, direct audit or large surveys of the residents face constraints, such
      as data availability and comparability, when used to study communities in
      countries in diverse parts of the world. The aim of this study was to develop a
      method to evaluate features of the built environment of communities using a
      standard set of photos. In this report we describe the method of photo
      collection, photo analysis instrument development and inter-rater reliability of
      the instrument. METHODS/PRINCIPAL FINDINGS: A minimum of 5 photos were taken per
      community in 86 communities in 5 countries according to a standard set of
      instructions from a designated central point of each community by researchers at
      each site. A standard pro forma derived from reviewing existing instruments to
      assess the built environment was developed and used to score the characteristics
      of each community. Photo sets from each community were assessed independently by
      three observers in the central research office according to the pro forma and the
      inter-rater reliability was compared by intra-class correlation (ICC). Overall
      87% (53 of 60) items had an ICC of >= 0.70, 7% (4 of 60) had an ICC between 0.60
      and 0.70 and 5% (3 of 60) items had an ICC <= 0.50. CONCLUSIONS/SIGNIFICANCE:
      Analysis of photos using a standardized protocol as described in this study
      offers a means to obtain reliable and reproducible information on the built
      environment in communities in very diverse locations around the world. The
      collection of the photographic data required minimal training and the analysis
      demonstrated high reliability for the majority of items of interest.

PMID- 25369367
TI  - beta-Lactam estrogen receptor antagonists and a dual-targeting estrogen
      receptor/tubulin ligand.
AB  - Twelve novel beta-lactams were synthesized and their antiproliferative effects
      and binding affinity for the predominant isoforms of the estrogen receptor (ER),
      ERalpha and ERbeta, were determined. beta-Lactams 23 and 26 had the strongest
      binding affinities for ERalpha (IC50 values: 40 and 8 nM, respectively) and
      ERbeta (IC50 values: 19 and 15 nM). beta-Lactam 26 was the most potent in
      antiproliferative assays using MCF-7 breast cancer cells, and further biochemical
      analysis showed that it caused accumulation of cells in G2/M phase (mitotic
      blockade) and depolymerization of tubulin in MCF-7 cells. Compound 26 also
      induced apoptosis and downregulation of the expression of pro-survival proteins
      Bcl-2 and Mcl-1. Computational modeling predicted binding preferences for the
      dual ER/tubulin ligand 26. This series is an important addition to the known pool
      of ER antagonists and beta-lactam 26 is the first reported compound that has dual
      targeting properties for both the ER and tubulin. 

PMID- 25369368
TI  - Epigenetic alterations in acute myeloid leukemias.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease for which the standard
      treatment with cytotoxic chemotherapy has remained largely unchanged for over
      four decades, with unfavorable clinical results. Epigenetic alterations have been
      described in several AMLs, and in some cases their origin has been studied in
      detail mechanistically (such as in acute promyelocytic leukemia, caused by the
      promyelocytic leukemia-retinoic acid receptor-alpha fusion protein). Recently,
      the advent of massive parallel sequencing has revealed that > 70% of AML cases
      have mutations in DNA methylation-related genes or mutations in histone
      modifiers, showing that epigenetic alterations are key players in the development
      of most, if not all, AMLs, and pointing to the exploitation of new molecular
      targets for more efficacious therapies. This review provides a brief overview of
      the latest findings on the characterization of the epigenetic landscape of AML
      and discusses the rationale for the optimization of epigenetic therapy of AML.

PMID- 25369369
TI  - Estimating a path through a map of decision making.
AB  - Studies of the evolution of collective behavior consider the payoffs of
      individual versus social learning. We have previously proposed that the relative
      magnitude of social versus individual learning could be compared against the
      transparency of payoff, also known as the "transparency" of the decision, through
      a heuristic, two-dimensional map. Moving from west to east, the estimated
      strength of social influence increases. As the decision maker proceeds from south
      to north, transparency of choice increases, and it becomes easier to identify the
      best choice itself and/or the best social role model from whom to learn
      (depending on position on east-west axis). Here we show how to parameterize the
      functions that underlie the map, how to estimate these functions, and thus how to
      describe estimated paths through the map. We develop estimation methods on
      artificial data sets and discuss real-world applications such as modeling changes
      in health decisions. 

PMID- 25369370
TI  - The impact of tracking system properties on the most likely path estimation in
      proton CT.
AB  - Proton CT nowadays aims at improving hadron therapy treatment planning by mapping
      the stopping power of materials. In order to optimize a spatial resolution of the
      reconstructed images, the most likely path (MLP) of each proton can be computed.
      We investigated the errors in the computation of this path due to the
      configuration of the system, i.e. the spatial resolution of the tracking planes,
      their material budget, and their positioning. A method for computing the
      uncertainty in the estimated paths for a given system was derived. The
      uncertainties upon the entrance and exit of the object were propagated
      analytically in the path computation. This procedure was then used to evaluate
      the impact of each parameter, and to compare different systems. We show that the
      intrinsic characteristics of the system generate an uncertainty in the positions
      and directions of the particles propagated during the MLP computation. The
      spatial resolution and material budget of the trackers in particular may affect
      the path estimation, and thus the spatial resolution of an image. 

PMID- 25369371
TI  - Quantitative analysis on collagen of dermatofibrosarcoma protuberans skin by
      second harmonic generation microscopy.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a skin cancer usually mistaken as other
      benign tumors. Abnormal DFSP resection results in tumor recurrence. Quantitative
      characterization of collagen alteration on the skin tumor is essential for
      developing a diagnostic technique. In this study, second harmonic generation
      (SHG) microscopy was performed to obtain images of the human DFSP skin and normal
      skin. Subsequently, structure and texture analysis methods were applied to
      determine the differences in skin texture characteristics between the two skin
      types, and the link between collagen alteration and tumor was established.
      Results suggest that combining SHG microscopy and texture analysis methods is a
      feasible and effective method to describe the characteristics of skin tumor like
      DFSP.

PMID- 25369372
TI  - Antibody-mediated rejection in lung transplantation: fable, spin, or fact?
AB  - The lung transplant community continues to struggle with the diagnosis and
      management of antibody-mediated rejection. The four diagnostic tenets of donor
      specific antibodies, C4d staining, histopathologic changes, and allograft
      dysfunction, which were largely derived from the early Banff meetings on renal
      transplantation, have somewhat arbitrarily been applied to lung transplantation.
      With the passage of time, it is increasingly apparent that merits of these
      diagnostic pillars are less robust in lung transplantation. In this article, we
      summarize some of the controversies and challenges surrounding the diagnosis of
      antibody-mediated rejection in lung transplantation. 

PMID- 25369373
TI  - Influence of oxygen concentration during hypothermic machine perfusion on porcine
      kidneys from donation after circulatory death.
AB  - BACKGROUND: Hypothermic machine perfusion (HMP) for preservation led to
      compelling success for outcomes of renal transplantation. Application of
      different concentrations of oxygen during renal HMP has not been systematically
      analyzed. This study investigates the aspects of renal function and morphology in
      dependence of oxygen concentrations during HMP in a porcine donation after
      circulatory death model. METHODS: After 30 min of warm ischemia, porcine kidneys
      were randomly assigned to preservation for 21 hr by HMP without oxygenation
      (HMPnoox), oxygenated HMP with air (HMPair), or 100% oxygen (HMPox100%).
      Afterward, kidneys were reperfused for 2 hr in an ex vivo model for assessment of
      function and integrity. RESULTS: Application of HMPox100% led to significantly
      increased blood flow during reperfusion compared to HMPnoox. Preservation by
      HMPox100% led to a doubling of creatinine clearance after 90 and 120 min of
      reperfusion (13.4 and 12.0 mL/min) compared to preservation by HMPnoox (7.3 and
      7.7 mL/min; P=0.01). Oxygenated HMP with air led to results between the two other
      groups. Fractional excretion of sodium demonstrated a strong tendency of higher
      values after HMPnoox compared to HMPox100% (P=0.096) and HMPair (P=0.09).
      Analysis of structural integrity during reperfusion demonstrated significantly
      higher values of lactate dehydrogenase resembling cell damage (P=0.02), higher
      values of gamma-glutamyl-transferase (gGT) resembling tubulus injury (P=0.048),
      and more pronounced tubular dilatation (P=0.02) after HMPnoox compared to
      HMPox100%. CONCLUSION: The present study demonstrates that application of
      HMPox100% for kidneys from donations after circulatory death results in better
      renal function during early reperfusion compared to HMPnoox.

PMID- 25369375
TI  - Professional growth.

PMID- 25369376
TI  - Relevance in the 21st century.

PMID- 25369374
TI  - A TIR domain protein from E. faecalis attenuates MyD88-mediated signaling and NF
      kappaB activation.
AB  - Toll-like receptor signaling, mediated by functional Toll/interleukin-1 receptor
      (TIR) domains, plays a critical role in activating the innate immune response
      responsible for controlling and clearing infection. Bacterial protein mimics of
      components of this signaling pathway have been identified and function through
      inhibition of interactions between Toll-like receptors (TLRs) and their adaptor
      proteins, mediated by TIR domains. A previously uncharacterized gene, which we
      have named tcpF (for TIR domain-containing protein in E. faecalis) was identified
      in the genome of Enterococcus faecalis V583, and predicted to encode a protein
      resembling mammalian and bacterial TIR proteins. We overexpressed and purified
      TcpF from E. coli and found that the recombinant protein could bind to
      phosphatidylinositol phosphates in vitro, suggesting a mechanism by which TcpF
      may be anchored to the plasma membrane in close proximity to TIR domains of TLRs
      and adaptor proteins. Purified TcpF was also found to interact specifically with
      the TIR adaptor protein MyD88, and this interaction was dependent on the BB loop
      domain in the Box 2 region of TcpF. Despite no evidence of TcpF being a secreted
      protein, recombinant TcpF was effectively able to enter RAW264.7 cells in vitro
      although the mechanism by which this occurs remains to be determined.
      Overexpression of TcpF in mammalian cells suppressed the NF-kappaB activation
      induced by bacterial lipoteichoic acid. A mutant lacking the tcpF gene was
      attenuated for survival in macrophages, with increased ability to activate NF
      kappaB compared to the wild type strain. Complementation in trans restored
      growth, and inhibition of NF-kappaB, to that of wild type levels. No appreciable
      difference in bacterial persistence, dissemination or pathogenesis was observed
      between the wild type and mutant in a mouse peritonitis model however, which
      suggested either a subtle role for TcpF or functional overlap with other
      redundant factor(s) in this virulence model. 

PMID- 25369377
TI  - Perpetuating old myths.

PMID- 25369379
TI  - Local anesthesia for restorative dentistry.

PMID- 25369378
TI  - Only informed patients can decide what serves them best.

PMID- 25369380
TI  - Predictable replacement of failing porcelain restorations.

PMID- 25369381
TI  - Gifts from patients.

PMID- 25369382
TI  - Conservative cosmetic dentistry post-trauma.
AB  - Traumatized teeth can bleed internally, causing discoloration over time. When
      this occurs in the smile zone, masking the dark colorations can present
      challenges when attempting to practice conservative cosmetic dentistry.
      Implementing nonvital bleaching can significantly improve the dark colorations of
      the traumatized teeth and support very conservative cosmetic dentistry. Effective
      communication with the ceramist is essential to ensure the desired results. This
      article presents a case involving trauma with delayed root canal therapy on tooth
      No. 9, which produced a very dark front tooth, and the conservative treatment
      plan chosen to correct it through the use of nonvital bleaching and feldspathic
      veneers requiring zero or minimal preparation.

PMID- 25369383
TI  - Shade evaluation of ceramic laminates according to different try-in materials.
AB  - The porcelain laminate replaces the visible portion of enamel with a ceramic,
      which is attached to the dental surface. To enhance cosmetic results, a
      preliminary color matching procedure is performed prior to cementing the veneers.
      This procedure can be performed using water, water-soluble gel, or try-in paste.
      The different shades of cement and try-in pastes are intended to obtain better
      color and esthetics of the final restoration. This study sought to evaluate the
      shade of ceramic veneers produced by different try-in materials. Forty bovine
      teeth and 40 ceramic discs (0.6 mm thick) were prepared. The samples were divided
      into 4 groups (n = 10). For Group 1 samples, no material was used between the
      tooth and the ceramic, Group 2 interposed samples with water, Group 3 used a
      water-soluble gel, and Group 4 used try-in paste (value 0). The color was
      measured with a spectrophotometer, obtaining L*, a*, and b* values to calculate
      the color difference (DeltaE*). The data were subjected to normality tests and 1
      way ANOVA. No significant statistical differences were found among the groups,
      indicating that the different try-in materials had similar effects on the color
      of the ceramic laminates. 

PMID- 25369384
TI  - Achieving highly esthetic anterior restorations with ideal assessment,
      communication, and technique.
AB  - Although all cases should be approached comprehensively, restoring a limited
      segment in the esthetic zone presents challenges particularly related to
      microesthetics. Microesthetics are those criteria related to the subtle
      intricacies of shade, textures, translucencies, and surface effects that make
      teeth look like teeth. These are the criteria that aid dentists in fooling the
      eye and allowing restorations to blend invisibly into the smile. Completing a
      comprehensive assessment of a patient ensures that the restorative foundation
      will remain biologically and structurally predictable, durable, and above all,
      esthetically pleasing. Starting esthetic treatment without first doing a
      comprehensive assessment will result in a compromised result. Within the criteria
      of microesthetics, the utilization of a common nomenclature and quantitative
      means of communication between the restorative dentist and the laboratory
      ceramist are at the core of success. The use of prototypes during the
      provisionalization phase and progressive techniques in digital photography are
      invaluable tools. Along with traditional techniques in acquiring proper shade
      selection, the use of cross-polarization filters has been proven to be an
      effective way to eliminate spectral artifacts typically found in flash
      photography. Additionally, the use of a color-corrected master die system
      provides the ceramist a method to calibrate shades on the lab bench by capturing
      images--via the cross-polarization filters--that are similar to what is observed
      clinically.

PMID- 25369385
TI  - A minimally invasive smile enhancement.
AB  - Minimally invasive dentistry refers to a wide variety of dental treatments. On
      the restorative aspect of dental procedures, direct resin bonding can be a very
      conservative treatment option for the patient. When tooth structure does not need
      to be removed, the patient benefits. Proper treatment planning is essential to
      determine how conservative the restorative treatment will be. This article
      describes the diagnosis, treatment options, and procedural techniques in the
      restoration of 4 maxillary anterior teeth with direct composite resin. The
      procedural steps are reviewed with regard to placing the composite and the
      variety of colors needed to ensure a natural result. Finishing and polishing of
      the composite are critical to ending with a natural looking dentition that the
      patient will be pleased with for many years.

PMID- 25369386
TI  - Comparison between visual and instrumental methods for natural tooth shade
      matching.
AB  - Tooth shade matching in daily clinical practice is still a cause of discomfort
      for many professionals due to the subjectivity of the process and the need for
      advanced training; this discomfort may lead to unsatisfactory results for the
      clinician and the patient. Instrumental methods were developed to simplify daily
      color matching procedures and to provide better esthetic outcomes. This study
      compared the accuracy of shade matching by both visual and instrumental methods
      to determine whether the instrumental method would significantly improve the
      process. Visual shade matching was performed by 4 dentists using a classic shade
      guide; instrumental shade matching was performed with a spectrophotometer by a
      previously calibrated examiner. Shade matching was conducted in a dental clinic
      under controlled illumination on the middle third of the right central incisor
      tooth of 30 subjects. Data were analyzed by Cohen's Kappa inter-rater agreement
      and by the equality of 2 proportions test (alpha = 0.05). Results showed
      statistically significant differences between the groups (76.7 +/- 11.1% and
      32.4% +/- 7.8% for the instrumental and visual methods, respectively). Shade
      matching by clinicians using the instrumental method presented more agreement,
      and was more effective than shade matching by clinicians using the visual method.

PMID- 25369387
TI  - Diagnosis, treatment, and risk management for a victim of domestic abuse: a case
      report.
AB  - A 37-year-old woman was referred to the author by the American Academy of
      Cosmetic Dentistry's "Give Back a Smile" program. The program helps facilitate
      dental treatment and support services for adults who have suffered dental
      injuries to the smile zone as a result of domestic or sexual violence. The woman
      presented with a broken jaw and fractured teeth. This case report describes the
      treatment planning decisions and a successful outcome. 

PMID- 25369388
TI  - Direct or indirect composite veneers in anterior teeth: which method causes
      higher tooth mass loss? An in vitro study.
AB  - There is little information in the literature regarding the relationship between
      preparations made for direct and indirect veneers and the loss of tooth structure
      required for each technique. This in vitro study sought to quantify the different
      mass losses from preparation techniques used for direct and indirect veneers.
      Thirty artificial teeth were weighted using a digital balance and placed in a
      dental manikin in the position corresponding to the right maxillary central
      incisor. Five clinicians-all experts in esthetic dentistry-were asked to perform
      conventional preparations for both a direct composite resin veneer and an
      indirect ceramic veneer. After preparations, specimens were weighted again in the
      same digital balance. Teeth undergoing veneer preparations demonstrated a
      statistically significant mass loss compared to unprepared teeth. Indirect
      ceramic veneer preparations produced more mass loss than direct composite veneer
      preparations (P < 0.01). 

PMID- 25369389
TI  - Approaches to managing asymptomatic enamel and dentin cracks.
AB  - Asymptomatic enamel and dentin cracks can pose a risk for multiple pathological
      and undesired consequences if intervention is postponed. This article reviews
      asymptomatic enamel and dentin cracks, and presents current management approaches
      utilized by a sample of general dentists. Becoming familiar with all forms of
      asymptomatic enamel and dentin cracks is crucial to adopting a proactive approach
      of prevention, early diagnosis, and intervention in order to control the
      potential detrimental effects of these cracks on the dentition. 

PMID- 25369390
TI  - Perspective of cardiologists on the continuation or discontinuation of
      antiplatelet therapy before dental treatment: a questionnaire-based study.
AB  - Antiplatelet and anticoagulant agents have been extensively researched and
      developed as potential therapies in the prevention and management of arterial and
      venous thrombi. These medications are associated with an increase in bleeding
      time and risk of intraoperative and postoperative hemorrhage in the dental
      office. There is some controversy regarding whether these agents should be
      temporarily discontinued before dental procedures. In order to gain insight into
      this controversy, a survey of 50 cardiologists was conducted regarding suggested
      guidelines for dentists in the management of patients who are taking
      anticoagulant medication.

PMID- 25369391
TI  - Mepivacaine: a closer look at its properties and current utility.
AB  - The use of mepivacaine in dentistry has remained strong since its introduction in
      the 1960s. It has retained its place as a valuable local anesthetic, either as a
      primary agent or as an alternative to lidocaine or articaine. Mepivacaine is
      commonly used in medically compromised patients--for whom elevations in blood
      pressure or heart rate are not advisable--in a formulation with a
      vasoconstrictor, or in pediatric populations in a formulation without a
      vasoconstrictor. Pharmacologically, these are the 2 groups most susceptible to
      side effects and toxicity, thus mepivacaine is commonly indicated. Most often the
      decision to use mepivacaine is based on its vasoconstrictor effect or lack
      thereof (depending on the formulation). However, the pharmacokinetics of
      mepivacaine are not well understood or assumed to be similar to that of other
      local anesthetics. It is important to understand the unique pharmacologic
      characteristics of mepivacaine in order to minimize the potential for inadvertent
      toxicity.

PMID- 25369392
TI  - A direct approach for fabrication of a provisional restoration immediately after
      tooth preparation for custom cast dowel and core.
AB  - When a tooth is fractured at the gingival level due to accidental trauma and
      there is insufficient coronal tooth structure to retain a crown, a custom cast
      dowel and core often is necessary, followed by the fabrication of a definitive
      crown. It is very difficult to fabricate the provisional restoration for a tooth
      until the custom cast dowel and core are cemented permanently. This article
      describes a direct procedure for fabricating a provisional restoration (with a
      prefabricated temporary titanium post and an acrylic resin denture tooth)
      immediately after the tooth has been prepared for a custom cast dowel and core.
      This technique produces excellent clinical results while being less time
      consuming than an indirect approach.

PMID- 25369393
TI  - The efficacy of 2 different doses of dexamethasone to control postoperative
      swelling, trismus, and pain after third molar extractions.
AB  - This article addresses the effect of 2 different concentrations (4 and 12 mg) of
      dexamethasone to control pain, swelling, and trismus after third molar surgery. A
      clinical study was conducted with 27 male and female patients, all presenting
      with bilaterally displaced mandibular third molars. The treatment protocol
      required a surgical removal of each tooth in 2 separate operations. The patients
      were given a preoperative dose of dexamethasone-4 mg for one surgery, 12 mg for
      the other. The choice of which side would be operated on first and which dose of
      dexamethasone would be taken was performed randomly, under double-blind
      conditions. The trismus was assessed by measuring the interincisal distance. Pain
      intensity was measured both by the amount of painkillers (acetaminophen 750 mg)
      taken postsurgery and by the Visual Analogue Pain Scale. Data were collected 1
      hour preoperative, then at 24 and 48 hours postoperative. A statistical analysis
      (student's t, Wilcoxon and Friedman tests) of the results showed no significant
      differences (alpha = 0.05) between the analyzed variables for the 2 doses of
      dexamethasone (4 and 12 mg).

PMID- 25369394
TI  - Cytotoxicity of dentin bonding agents.
AB  - This study sought to evaluate the cytotoxicity of 5 dentin bonding agents (Admira
      Bond, Adper Single Bond Plus, Clearfil SE Bond, Clearfil S3 Bond, and Heliobond)
      by XTT assay using human gingival fibroblast cells. Samples of dentin bonding
      agents were prepared on a black 96-well microplate, and the cytotoxicity of each
      bonding material was measured every 24 hours for 7 days, then on Days 14, 21, and
      28. One-way ANOVA and Bonferroni post hoc tests were used for statistical
      analyses. All 5 materials were evaluated as severely cytotoxic (P < 0.001) on the
      first day, with cell viabilities ranging from 6% to 24%. All the bonding agents
      showed severe cytotoxicity with viability results <10%. With the exception of
      Adper Single Bond Plus, toxicity continued to Day 28 for all compounds. The
      utmost care must be considered during the clinical utilization of dentin bonding
      agents to keep them within the area of restoration and prevent their contact with
      adjacent tissues.

PMID- 25369395
TI  - Surgical crown lengthening: a periodontal and restorative interdisciplinary
      approach.
AB  - Surgical crown lengthening helps to provide an adequate retention form for proper
      tooth preparation, thus enabling dentists to create esthetically pleasing and
      healthy restorations. Long-term stability requires accurate diagnosis and
      development of a comprehensive treatment plan in each case. This sequence of
      events stresses the importance of communication between the restorative dentist
      and the periodontist. This article presents 2 cases that involve surgical crown
      lengthening (including mucoperiosteal flap and ostectomy) for the restoration of
      teeth.

PMID- 25369396
TI  - Surface roughness of different composite resins subject to in-office bleaching.
AB  - This study used atomic force microscopy to evaluate the effects of an in-office
      dental bleaching protocol on the surface roughness of 3 resins: microfilled,
      microhybrid, and nanofilled. Two disks of each resin were prepared and evaluated.
      Twenty-four areas (5 x 5 um) were scanned using an atomic force microscope. Then,
      each disk was treated with 35% hydrogen peroxide activated by a light emitting
      diode. After bleaching, the disks were scanned again. Data from the 24 areas
      before and after bleaching were evaluated qualitatively using topographical and 3
      dimensional images, as well as profile lines. Quantitatively, roughness data
      (mean roughness and root mean square) were statistically evaluated using standard
      ANOVA and Student-Newman-Keuls tests (P < 0.05). The bleaching procedure
      increased roughness for each resin analyzed. Based on the results, it was
      concluded that in-office bleaching with 35% hydrogen peroxide-based gel
      significantly increased the surface roughness of microfilled, microhybrid, and
      nanofilled resins. 

PMID- 25369397
TI  - An in vitro comparison of antimicrobial toothbrushes.
AB  - The purpose of this study was to determine the efficacy of toothbrushes that
      advertise self-disinfecting, antimicrobial properties due to the inclusion of
      silver nanoparticles or chlorhexidine in the bristles. Three different types of
      toothbrushes-silver nanoparticle, chlorhexidine-coated, and a control-were
      submerged in suspensions of Streptococcus mutans and Candida albicans. At
      designated times postinoculation, organisms were removed from the toothbrush
      heads, then serially diluted, plated, and incubated. The colony-forming units
      (CFUs) were counted and a mean percent reduction was determined for each organism
      group. With the S. mutans groups, the chlorhexidine-coated toothbrushes had
      significantly greater percent reduction in CFUs at all 3 time points compared to
      the control or silver nanoparticle toothbrushes. With the C. albicans groups,
      neither the chlorhexidine-coated nor the silver nanoparticle toothbrushes had a
      significant reduction in CFUs compared to the control. Neither of the
      antimicrobial toothbrushes delivered the advertised claim of a 99.9% reduction in
      CFUs with either microorganism. However, the inclusion of chlorhexidine in
      toothbrush bristles appeared to be the most promising of the methods tested for
      toothbrush self-disinfection.

PMID- 25369398
TI  - Evaluation of the association between periodontal disease and diabetic
      retinopathy.
AB  - Periodontitis may act as a risk factor for diabetes and its various complications
      such as cardiorenal complications. The current literature is deficient regarding
      the association between periodontal disease and diabetic retinopathy (DR). This
      cross-sectional study of 100 type II diabetes patients sought to evaluate the
      association of periodontal disease with the occurrence and severity of DR. The
      results showed a definite association between periodontal disease status and the
      occurrence of DR, although a cause and effect relationship could not be
      established. 

PMID- 25369399
TI  - An association between temporomandibular disorder and gum chewing.
AB  - This single center, randomized, small study sought to investigate the prevalence
      and frequency of chewing gum consumption, and whether there is a relationship
      between these factors and the presence of symptoms associated with
      temporomandibular disorder (TMD). Subjects were divided into 7 groups based on
      their parafunctional oral habits. Of these, subjects who chewed gum were divided
      into 5 subgroups (A-E) based on their gum chewing habits. Group A chewed gum <1
      hour/day (n = 12), Group B chewed gum 1-2 hours/day (n = 11), Group C chewed gum
      3 hours/day (n = 6), and Group D chewed gum >3 hours at a time (n = 8); the
      frequency of gum chewing in Groups A-D was once a week. Group E subjects chewed
      gum 1-3 times/week for at least 1 hour each occurrence (n = 2). Sixty-three
      percent of the subjects in Group D reported TMD symptoms of arthralgia and
      myofascial pain. Thirty-three percent of the subjects in Group C showed symptoms
      of arthralgia. Eighty-three percent of the subjects in Group A and 27% in Group B
      reported myofascial pain. All subjects in Group E reported masseter hypertrophy.
      The remaining 2 groups were Group F, subjects that didn't chew gum but had other
      parafunctional oral habits (n = 2), and Group G, subjects who didn't have
      parafunctional oral habits (n = 12). 

PMID- 25369400
TI  - Clinical evaluation of silorane-based and dimethacrylate-based resin composites:
      1-year follow-up.
AB  - This study sought to evaluate the 1-year clinical performance of silorane-based
      and dimethacrylate-based Class II resin composite restorations using 2 bonding
      strategies. Eighty-two restorations were placed in 32 patients (median age 37
      years) by a single operator. Only Class II restorations were included. Each
      patient received 1-2 pairs of resin composite restorations with both restoration
      materials. Between-group comparisons were made using an adjusted chi-square test
      and an adjusted McNemar's chi-square test to analyze the intrasystem data (alpha
      = 0.05). Both systems demonstrated acceptable clinical performance after 1 year. 

PMID- 25369401
TI  - Detection and attribution of vegetation greening trend in China over the last 30
      years.
AB  - The reliable detection and attribution of changes in vegetation growth is a
      prerequisite for the development of strategies for the sustainable management of
      ecosystems. This is an extraordinary challenge. To our knowledge, this study is
      the first to comprehensively detect and attribute a greening trend in China over
      the last three decades. We use three different satellite-derived Leaf Area Index
      (LAI) datasets for detection as well as five different process-based ecosystem
      models for attribution. Rising atmospheric CO2 concentration and nitrogen
      deposition are identified as the most likely causes of the greening trend in
      China, explaining 85% and 41% of the average growing-season LAI trend (LAIGS)
      estimated by satellite datasets (average trend of 0.0070 yr(-1), ranging from
      0.0035 yr(-1) to 0.0127 yr(-1)), respectively. The contribution of nitrogen
      deposition is more clearly seen in southern China than in the north of the
      country. Models disagree about the contribution of climate change alone to the
      trend in LAIGS at the country scale (one model shows a significant increasing
      trend, whereas two others show significant decreasing trends). However, the
      models generally agree on the negative impacts of climate change in north China
      and Inner Mongolia and the positive impact in the Qinghai-Xizang plateau.
      Provincial forest area change tends to be significantly correlated with the trend
      of LAIGS (P < 0.05), and marginally significantly (P = 0.07) correlated with the
      residual of LAIGS trend, calculated as the trend observed by satellite minus that
      estimated by models through considering the effects of climate change, rising CO2
      concentration and nitrogen deposition, across different provinces. This result
      highlights the important role of China's afforestation program in explaining the
      spatial patterns of trend in vegetation growth.

PMID- 25369402
TI  - Discoidin domain receptor 1 contributes to tumorigenesis through modulation of
      TGFBI expression.
AB  - Discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase
      family. The receptor is activated upon binding to its ligand, collagen, and plays
      a crucial role in many fundamental processes such as cell differentiation,
      adhesion, migration and invasion. Although DDR1 is expressed in many normal
      tissues, upregulated expression of DDR1 in a variety of human cancers such as
      lung, colon and brain cancers is known to be associated with poor prognosis.
      Using shRNA silencing, we assessed the oncogenic potential of DDR1. DDR1
      knockdown impaired tumor cell proliferation and migration in vitro and tumor
      growth in vivo. Microarray analysis of tumor cells demonstrated upregulation of
      TGFBI expression upon DDR1 knockdown, which was subsequently confirmed at the
      protein level. TGFBI is a TGFbeta-induced extracellular matrix protein secreted
      by the tumor cells and is known to act either as a tumor promoter or tumor
      suppressor, depending on the tumor environment. Here, we show that exogenous
      addition of recombinant TGFBI to BXPC3 tumor cells inhibited clonogenic growth
      and migration, thus recapitulating the phenotypic effect observed from DDR1
      silencing. BXPC3 tumor xenografts demonstrated reduced growth with DDR1
      knockdown, and the same xenograft tumors exhibited an increase in TGFBI
      expression level. Together, these data suggest that DDR1 expression level
      influences tumor growth in part via modulation of TGFBI expression. The
      reciprocal expression of DDR1 and TGFBI may help to elucidate the contribution of
      DDR1 in tumorigenesis and TGFBI may also be used as a biomarker for the
      therapeutic development of DDR1 specific inhibitors. 

PMID- 25369403
TI  - Testing madness: shifting from a punitive approach to a therapeutic one.

PMID- 25369404
TI  - Shared vulnerabilities in research.
AB  - The U.S. Code of Federal Regulations governing federally funded research on human
      subjects assumes that harmful research is sometimes morally justifiable because
      the beneficiaries of that research share a particular vulnerability with its
      subjects. In this article, I argue against this assumption, which occurs in every
      subpart of the Code of Federal Regulations that deals with specific vulnerable
      populations (pregnant women, fetuses, neonates, prisoners, and children). I argue
      that shared vulnerability is no exception to the general principle that harming
      one person in order to benefit another is no more justifiable if the two people
      have traits in common. Further, shared vulnerability is not a reasonable proxy
      for any morally relevant desideratum of research, in particular the desire to
      benefit the worst off, the desire to avoid exploitation, and the desire to use
      vulnerable populations in research only when necessary. 

PMID- 25369405
TI  - Locating the right rationale: phase I.

PMID- 25369406
TI  - The ethical principle of scientific necessity in pediatric research.

PMID- 25369407
TI  - Vulnerability: its meaning and value in the context of contemporary bioethics.

PMID- 25369408
TI  - The vulnerability of the individual benefit argument.

PMID- 25369409
TI  - Problems of specificity: an indirect argument for Chwang's position.

PMID- 25369410
TI  - Shifting the balance: equalizing protection for both participants and
      beneficiaries of research.

PMID- 25369411
TI  - Two kinds of to-kind benefits and other reasons why shared vulnerability can keep
      clinical studies ethical.

PMID- 25369412
TI  - Alcohol and drug testing of health professionals following preventable adverse
      events: a bad idea.
AB  - Various kinds of alcohol and drug testing, such as preemployment, routine, and
      for-cause testing, are commonly performed by employers. While healthcare
      organizations usually require preemployment drug testing, they vary on whether
      personnel will be subjected to further testing. Recently, a call has gone out for
      postincident testing among physicians who are involved in serious, preventable
      events, especially ones leading to a patient's death. This article will offer a
      number of counterarguments to that proposal and discuss an alternate approach:
      that health institutions can better improve patient safety and employees' well
      being by implementing an organizational policy of "speaking up" when system
      operators notice work behaviors or environmental factors that threaten harm or
      peril. The article will conclude with a description of various strategies that
      facilitate speaking up, and why the practice constitutes a superior alternative
      to mandatory alcohol and drug testing in the wake of serious, harm-causing
      medical error. 

PMID- 25369413
TI  - Postincident alcohol and drug testing.

PMID- 25369414
TI  - Drug testing of health care professionals to improve overall wellness and patient
      care.

PMID- 25369415
TI  - Addicted health care professionals: missing the wood for the trees?

PMID- 25369416
TI  - Unintended effects on morale of mandatory postincident testing.

PMID- 25369417
TI  - On speaking up and alcohol and drug testing for health care professionals.

PMID- 25369419
TI  - A response to the open peer commentaries on "patient and citizen participation in
      health: the need for improved ethical support".

PMID- 25369420
TI  - High-efficiency plasmon-enhanced and graphene-supported semiconductor/metal core
      satellite hetero-nanocrystal photocatalysts for visible-light dye
      photodegradation and H2 production from water.
AB  - Solar-driven photocatalytic process based on electron-hole pair production in
      semiconductors is a long sought-after solution to a green and renewable energy
      and has attracted a renaissance of interest recently. The relatively low
      photocatalytic efficiency, however, is a main obstacle to their practical
      applications. A promising attempt to solve this problem is by combined use of
      metal nanoparticles, by taking advantage of strong and localized plasmonic near
      field to enhance solar absorption and to increase the electron-hole pair
      generation rate at the surface of semiconductor. Here, we report a
      semiconductor/metal visible-light photocatalyst based on CdSe/CdS-Au (QD-Au) core
      satellite heteronanocrystals, and assemble them on graphene nanosheets for better
      photocatalytic reaction. The as-synthesized photocatalyst exhibits excellent
      plasmon-enhanced photocatalytic activities toward both photodegradation of
      organic dye and visible-light H2 generation from water. The H2 evolution rate
      achieves a maximum of 3113 MUmol h(-1) g(-1) for the heteronanocrystal-graphene
      composites, which is about 155% enhancement compared to nonplasmonic QD-G sample
      and 340% enhancement compared to control QD-Au-G sample, and the apparent quantum
      efficiency (QE) reaches to 25.4% at wavelength of 450 nm. 

PMID- 25369422
TI  - Decomposition of diazomeldrum's acid: a threshold photoelectron spectroscopy
      study.
AB  - Derivatives of meldrum's acid are known precursors for a number of reactive
      intermediates. Therefore, we investigate diazomeldrum's acid (DMA) and its
      pyrolysis products by photoionization using vacuum ultraviolet (VUV) synchrotron
      radiation. The threshold photoelectron spectrum of DMA yields an ionization
      energy (IE) of 9.68 eV. Several channels for dissociative photoionization are
      observed. The first one is associated with loss of CH3, leading to a daughter ion
      with m/z = 155. Its appearance energy AE0K was determined to be 10.65 eV by
      fitting the experimental data using statistical theory. A second parallel channel
      leads to m/z = 69, corresponding to N2CHCO, with an AE0K of 10.72 eV. Several
      other channels open up at higher energy, among them the formation of acetone
      cation, a channel expected to be the result of a Wolff-rearrangement (WR) in the
      cation. When diazomeldrum's acid is heated in a pyrolysis reactor, three thermal
      decomposition pathways are observed. The major one is well-known and yields
      acetone, N2 and CO as consequence of the WR. However, two further channels were
      identified: The formation of 2-diazoethenone, NNCCO, together with acetone and
      CO2 as the second channel and E-formylketene (OCCHCHCO), propyne, N2 and O2 as a
      third one. 2-Diazoethenone and E-formylketene were identified based on their
      threshold photoelectron spectra and accurate ionization energies could be
      determined. Ionization energies for several isomers of both molecules were also
      computed. One of the key findings of this study is that acetone is observed upon
      decomposition of DMA in the neutral as well as in the ion and both point to a
      Wolff rearrangement to occur. However, the ion is subject to other decomposition
      channels favored at lower internal energies. 

PMID- 25369421
TI  - Genetic mapping and QTL analysis of growth-related traits in Pinctada fucata
      using restriction-site associated DNA sequencing.
AB  - The pearl oyster, Pinctada fucata (P. fucata), is one of the marine bivalves that
      is predominantly cultured for pearl production. To obtain more genetic
      information for breeding purposes, we constructed a high-density linkage map of
      P. fucata and identified quantitative trait loci (QTL) for growth-related traits.
      One F1 family, which included the two parents, 48 largest progeny and 50 smallest
      progeny, was sampled to construct a linkage map using restriction site-associated
      DNA sequencing (RAD-Seq). With low coverage data, 1956.53 million clean reads and
      86,342 candidate RAD loci were generated. A total of 1373 segregating SNPs were
      used to construct a sex-average linkage map. This spanned 1091.81 centimorgans
      (cM), with 14 linkage groups and an average marker interval of 1.41 cM. The
      genetic linkage map coverage, Coa, was 97.24%. Thirty-nine QTL-peak loci, for
      seven growth-related traits, were identified using the single-marker analysis,
      nonparametric mapping Kruskal-Wallis (KW) test. Parameters included three for
      shell height, six for shell length, five for shell width, four for hinge length,
      11 for total weight, eight for soft tissue weight and two for shell weight. The
      QTL peak loci for shell height, shell length and shell weight were all located in
      linkage group 6. The genotype frequencies of most QTL peak loci showed
      significant differences between the large subpopulation and the small
      subpopulation (P<0.05). These results highlight the effectiveness of RAD-Seq as a
      tool for generation of QTL-targeted and genome-wide marker data in the non-model
      animal, P. fucata, and its possible utility in marker-assisted selection (MAS). 

PMID- 25369425
TI  - Lock-arm supramolecular ordering: a molecular construction set for
      cocrystallizing organic charge transfer complexes.
AB  - Organic charge transfer cocrystals are inexpensive, modular, and solution
      processable materials that are able, in some instances, to exhibit properties
      such as optical nonlinearity, (semi)conductivity, ferroelectricity, and
      magnetism. Although the properties of these cocrystals have been investigated for
      decades, the principal challenge that researchers face currently is to devise an
      efficient approach which allows for the growth of high-quality crystalline
      materials, in anticipation of a host of different technological applications. The
      research reported here introduces an innovative design, termed LASO-lock-arm
      supramolecular ordering-in the form of a modular approach for the development of
      responsive organic cocrystals. The strategy relies on the use of aromatic
      electronic donor and acceptor building blocks, carrying complementary rigid and
      flexible arms, capable of forming hydrogen bonds to amplify the cocrystallization
      processes. The cooperativity of charge transfer and hydrogen-bonding interactions
      between the building blocks leads to binary cocrystals that have alternating
      donors and acceptors extending in one and two dimensions sustained by an
      intricate network of hydrogen bonds. A variety of air-stable, mechanically
      robust, centimeter-long, organic charge transfer cocrystals have been grown by
      liquid-liquid diffusion under ambient conditions inside 72 h. These cocrystals
      are of considerable interest because of their remarkable size and stability and
      the promise they hold when it comes to fabricating the next generation of
      innovative electronic and photonic devices. 

PMID- 25369423
TI  - Genetic dissection of Gata2 selective functions during specification of V2
      interneurons in the developing spinal cord.
AB  - Motor activities are controlled by neural networks in the ventral spinal cord and
      consist in motor neurons and a set of distinct cardinal classes of spinal
      interneurons. These interneurons arise from distinct progenitor domains (p0-p3)
      delineated according to a transcriptional code. Neural progenitors of each domain
      express a unique combination of transcription factors (TFs) that largely
      contribute to determine the fate of four classes of interneurons (V0-V3) and
      motor neurons. In p2 domain, at least four subtypes of interneurons namely V2a,
      V2b, V2c, and Pax6(+) V2 are generated. Although genetic and molecular mechanisms
      that specify V2a and V2b are dependent on complex interplay between several TFs
      including Nkx6.1, Irx3, Gata2, Foxn4, and Ascl1, and signaling pathways such as
      Notch and TGF-beta, the sequence order of the activation of these regulators and
      their respective contribution are not completely elucidated yet. Here, we provide
      evidence by loss- or gain-of-function experiments that Gata2 is necessary for the
      normal development of both V2a and V2b neurons. We demonstrate that Nkx6.1 and
      Dll4 positively regulate the activation of Gata2 and Foxn4 in p2 progenitors.
      Gata2 also participates in the maintenance of p2 domain by repressing motor
      neuron differentiation and exerting a feedback control on patterning genes.
      Finally, Gata2 promotes the selective activation of V2b program at the expense of
      V2a fate. Thus our results provide new insights on the hierarchy and complex
      interactions between regulators of V2 genetic program.

PMID- 25369424
TI  - Dilated hearts at high altitude: words from on high.
AB  - From the time of the turn of the twentieth century, dilated hearts and presumed
      cardiac fatigue in expeditionary climbers and scientists have been the subject of
      much commentary in the medical and mountaineering literature. Although largely
      attributed by most, but not all, to left heart strain, the description of dilated
      hearts in these accounts is clearly that of right heart dilation as a consequence
      of high and sustained hypoxic pulmonary vasoconstriction with hypertensive
      remodeling. This essay will feature quotations from the writings of high altitude
      pioneers about dilated, strained, or enlarged hearts. It will give some brief
      physiology of the right side of the heart as background, but will focus on the
      words of mountaineers and mountaineering physicians as color commentary.

PMID- 25369426
TI  - 11C-acetate PET imaging in patients with multiple sclerosis.
AB  - BACKGROUND: Activation of glial cells is a cardinal feature in multiple sclerosis
      (MS) pathology, and acetate has been reported to be selectively uptaken by
      astrocytes in the CNS. The aim of this study was to investigate the efficacy of
      PET with (11)C-acetate for MS diagnosis. MATERIALS AND METHODS: Six patients with
      relapsing-remitting MS and 6 healthy volunteers (HV) were enrolled. The (11)C
      acetate brain uptake on PET was measured in patients with MS and HV. Volume-of
      interest analysis of cerebral gray and white matter based on the segmentation
      technique for co-registered MRI and voxel-based statistical parametric analysis
      were performed. Correlation between 11C-acetate uptake and the lesion number in
      T1- and T2- weighted MR images were also assessed. RESULTS: The standardized
      uptake value (SUV) of 11C-acetate was increased in both white and gray matter in
      MS patients compared to HV. Voxel-based statistical analysis revealed a
      significantly increased SUV relative to that in the bilateral thalami (SUVt) in a
      broad area of white matter, particularly in the subcortical white matter of MS
      patients. The numbers of T2 lesions and T1 black holes were significantly
      correlated with SUV of (11)C-acetate in white and gray matter. CONCLUSIONS: The
      11C-acetate uptake significantly increased in MS patients and correlated to the
      number of MRI lesions. These preliminary data suggest that (11)C-acetate PET can
      be a useful clinical examination for MS patients.

PMID- 25369427
TI  - Toxicity, bioaccumulation, and biotransformation of silver nanoparticles in
      marine organisms.
AB  - The toxicity, bioaccumulation, and biotransformation of citrate and
      polyvinylpyrrolidone (PVP) coated silver nanoparticles (NPs) (AgNP-citrate and
      AgNP-PVP) in marine organisms via marine sediment exposure was investigated.
      Results from 7-d sediment toxicity tests indicate that AgNP-citrate and AgNP-PVP
      did not exhibit toxicity to the amphipod (Ampelisca abdita) and mysid
      (Americamysis bahia) at <=75 mg/kg dry wt. A 28-d bioaccumulation study showed
      that Ag was significantly accumulated in the marine polychaete Nereis virens (N.
      virens) in the AgNP-citrate, AgNP-PVP and a conventional salt (AgNO3) treatments.
      Synchrotron X-ray absorption spectroscopy (XAS) results showed the distribution
      of Ag species in marine sediments amended with AgNP-citrate, AgNP-PVP, and AgNO3
      was AgCl (50-65%) > Ag2S (32-42%) > Ag metal (Ag0) (3-11%). In N virens, AgCl (25
      59%) and Ag2S (10-31%) generally decreased and, Ag metal (32-44%) increased,
      relative to the sediments. The patterns of speciation in the worm were different
      depending upon the coating of the AgNP and both types of AgNPs were different
      than the AgNO3 salt. These results show that the AgNP surface capping agents
      influenced Ag uptake, biotransformation, and/or excretion. To our knowledge, this
      is the first demonstration of the bioaccumulation and speciation of AgNPs in a
      marine organism (N. virens).

PMID- 25369428
TI  - Computational rationale for the selective inhibition of the herpes simplex virus
      type 1 uracil-DNA glycosylase enzyme.
AB  - The herpes simplex virus uracil-DNA glycosylase (hsvUNG) enzyme is responsible
      for the reactivation of the virus from latency and efficient viral replication in
      nerve tissue. The lack of uracil-DNA glycosylase enzyme in human neurons and the
      continuous deamination of cytosine create an environment where the presence of
      viral uracil-DNA glycosylase is a necessity for the proliferation of the virus. A
      series of 6-(4-alkylanilino)-uracil inhibitors has been developed that
      selectively and strongly binds to the hsvUNG enzyme while weakly binding to human
      uracil-DNA glycosylase (hUNG). Here, by using a combination of sequence and
      structural comparisons between the two enzymes along with free energy of binding
      computations and principal component analysis of the ligands, we investigate and
      rationalize the inhibitory effect of the 6-(4-alkylanilino)-uracil series as a
      function of alkyl chain length on the hsvUNG. The results of these computations
      corroborate the experimental finding that the inhibitor with an octyl aliphatic
      chain selectively binds hsvUNG best. More importantly we find that 6-(4
      octylanilino)-uracil's selective inhibition of hsvUNG over hUNG is due to the
      combination of the solution preconfigured bent conformation of that specific
      chain length and the position of HIS92 (absent in hUNG) just outside hsvUNG's
      hydrophobic gorge lying adjacent to its uracil binding pocket. The similarities
      between the uracil binding pockets in hsvUNG and hUNG obfuscate an understanding
      of the preferential inhibition of the virus enzyme. However, the differences in
      the enzymes' shallow hydrophobic grooves adjacent to the binding pockets, such as
      the gorge we identify here, rationalizes 6-(4-alkylanilino)-uracil with an octyl
      chain length as an excellent pharmacophore template for hsvUNG inhibitor design. 

PMID- 25369429
TI  - Informal science education: lifelong, life-wide, life-deep.
AB  - Informal Science Education: Lifelong, Life-Wide, Life-Deep Informal science
      education cultivates diverse opportunities for lifelong learning outside of
      formal K-16 classroom settings, from museums to online media, often with the help
      of practicing scientists. 

PMID- 25369430
TI  - Tracey A. Cho, MD, MA.

PMID- 25369431
TI  - Neurorheumatology.

PMID- 25369432
TI  - Clinical approach to neurorheumatology.
AB  - Rheumatologic conditions are an important cause of both central and peripheral
      nervous system pathology. A thorough evaluation for an underlying rheumatologic
      process is an important component of a patient presenting with neurologic
      symptoms. In this review, the authors present an approach to evaluating
      rheumatologic conditions, focusing primarily on the history and physical
      examination. They focus on the most specific signs and symptoms that may help the
      neurologist assess whether an underlying rheumatologic process is present. In
      addition, they discuss the interpretation of such findings with an eye toward
      narrowing the differential diagnosis and directing further testing. 

PMID- 25369433
TI  - Laboratory testing in neurorheumatology.
AB  - Laboratory testing in cases of neuro-rheumatologic disease can be daunting, and
      the results can be difficult to interpret if not placed in the correct clinical
      context. To best help our patients and also to practice in a cost-effective
      environment, laboratory testing must be performed in a logical manner, guided by
      symptoms and clinical judgment. The authors discuss the different laboratory
      tests used in the diagnosis and evaluation of rheumatologic diseases often
      encountered in the practice of neurology. It is important to understand how the
      tests are performed and which methods are used at your own institution. Testing
      should be ordered with a specific diagnosis in mind so as not to confuse the
      clinical picture with possible false-positive results. Through discussion of the
      various testing options, the authors advocate a step-wise approach to
      investigation. 

PMID- 25369434
TI  - Neurosarcoidosis.
AB  - Sarcoidosis is an idiopathic multisystem granulomatous disorder. Neurologic
      manifestations in sarcoidosis are varied and making a diagnosis of
      neurosarcoidosis can be difficult as it mimics various other neurologic diseases.
      Knowledge of the syndromes associated with neurosarcoidosis can help guide the
      diagnostic evaluation. Definitive diagnosis requires neurologic tissue evidence
      of noncaseating granuloma, but in practice probable diagnosis is often made
      through nonneurologic biopsy and a characteristic syndrome and imaging. Treatment
      remains empiric, but new advances in immunologic therapy hold promise for
      effective and less-toxic regimens. 

PMID- 25369435
TI  - IgG4-related disease and other causes of inflammatory meningeal disease.
AB  - Immunoglobulin-4 (IgG4-) related disease is a newly described treatable condition
      that has recently expanded the differential diagnosis of inflammatory meningeal
      disorders. This review will discuss the main clinical and pathophysiological
      features of IgG4-related meningeal disease in the context of meningeal
      inflammatory disorders in general. Particular attention will be dedicated to the
      differential diagnosis and the different therapeutic approaches. 

PMID- 25369436
TI  - CNS vasculitis.
AB  - Central nervous system vasculitis (CNSV) is a complex disease that poses
      considerable diagnostic and therapeutic challenges. It is divided into primary
      angiitis of the CNS (PACNS), or secondary angiitis of the CNS when associated
      with systemic conditions. Clinical presentation can be extremely variable and
      there is no classic presentation. In addition, there is no single diagnostic test
      and the sensitivity/specificity of all currently available tests is suboptimal.
      As such, an exhaustive approach with thorough historical data, physical
      examination, and corroborating investigations should be performed to exclude or
      confirm a diagnosis of CNSV. Infectious, neoplastic, and autoimmune conditions
      should be carefully evaluated. Knowledge of CNSV mimics is crucial given the
      therapeutic and prognostic implications. Reversible cerebral vasoconstriction
      syndrome is now recognized as the most common mimicker of PACNS. Much progress
      has been made in the understanding of PACNS histopathology, and specific clinical
      subsets and their response to treatment. Contrary to historical reports, recent
      PACNS cohorts achieved favorable clinical outcomes when early diagnosis and
      prompt treatment was initiated. Successful treatment with newer drugs has also
      been reported in PACNS cases. Newer imaging modalities hold promise for
      distinguishing inflammatory from noninflammatory vascular lesions. In this
      review, the authors provide a broad overview with updates on the types of adult
      CNSV along with its clinical assessment, diagnosis, and treatment. 

PMID- 25369437
TI  - Peripheral neuropathies of rheumatologic disease and gluten-related disorders.
AB  - Peripheral nervous system disease is a common and often debilitating feature of
      many systemic rheumatologic disorders. Such involvement takes many forms,
      reflecting the variety of underlying pathophysiology, though most patients
      present with painful multifocal neuropathy (usually vasculitic) or a distal
      sensory more than motor peripheral neuropathy (sometimes vasculitic and nearly
      always axonal). The presence of peripheral nervous system involvement is often an
      early signal of the generalization of inflammatory disease in blood vessels or
      extravascular tissues, though peripheral neuropathy is not itself an independent
      predictor of mortality. Nonetheless, progressive multifocal neuropathy, motor
      neuropathy, small fiber neuropathy, and sensory neuronopathy should be treated
      early and aggressively with immunosuppression (or the gluten-free diet in
      appropriate situations) to limit morbidity. Given the rapidly evolving
      therapeutic landscape, partnership with a rheumatologist is essential. Treatment
      is usually sustained for 1 to 2 years, and remission is possible in many cases
      within 6 to 12 months, with variable rates of relapse and treatment resistance.
      Patients should be meticulously monitored for relapse with serial laboratory
      testing, electrodiagnostic studies, and clinical examination. Functional rating
      scores, such as the neuropathy impairment scale and the total neuropathy score
      are useful for longitudinal assessment. 

PMID- 25369438
TI  - Neurologic complications of systemic lupus erythematosus, sjogren syndrome, and
      rheumatoid arthritis.
AB  - Neurologic complications are frequent and often morbid in systemic lupus
      erythematosus, Sjogren syndrome, and rheumatoid arthritis. Although all are
      systemic inflammatory syndromes, each disease affects the nervous system
      distinctly, such as peripheral neuropathy in Sjogren syndrome, cerebrovascular
      disease in lupus, and cervical spine subluxation in rheumatoid arthritis. Some
      neurologic complications share convergent pathophysiology across diseases, such
      as neuromyelitis optica spectrum disorders in both Sjogren syndrome and lupus.
      Ill-defined cognitive complaints are especially common in lupus and Sjogren
      syndrome. For the majority of the complications, evidence for treatment efficacy
      is limited and requires further investigation. 

PMID- 25369439
TI  - Neuro-Behcet disease and autoinflammatory disorders.
AB  - Misregulation of innate immunity leads to autoinflammation. Behcet disease is an
      autoinflammatory condition involving recurrent attacks of inflammation in skin,
      eyes, joints, and even the nervous system. The etiology may involve vascular
      inflammation. Central nervous system involvement in neuro-Behcet disease (NBD)
      comes in the form of parenchymal NBD or nonparenchymal NBD. The parenchymal form
      has a predilection for the brainstem, diencephalon and cerebral hemispheres, and
      represents a meningoencephalitis thought to be related to small vessel
      vasculitis. Cerebral venous sinus thrombosis, arising from a vasculitic process
      of large veins, comprises the majority of vascular NBD cases. The rarer
      monogenetic autoinflammatory syndromes are characterized by periodic fever, and
      typically present in the pediatric population. Neurologic involvement in these
      syndromes typically presents in the form of an aseptic meningitis. Treatment of
      autoinflammatory disorders involves immune modulation with corticosteroids,
      disease-modifying antirheumatic medications, and increasingly antibodies
      targeting cytokines like tumor necrosis factor alpha and interleukin 1. 

PMID- 25369440
TI  - Ocular inflammation in neurorheumatic disease.
AB  - Neuroimmunologic and systemic rheumatic diseases are frequently accompanied by
      inflammation of the eye, ocular adnexa, and orbital tissues. An understanding of
      the diverse forms of ophthalmic pathology in these conditions aids the clinician
      in making appropriate preventative, diagnostic, therapeutic, and prognostic
      decisions. In this review, the authors address ocular inflammation in
      neurorheumatic disease in three sections: first, they highlight current
      perspectives on immune mechanisms in the development of these disorders; next,
      they provide a framework for the recognition and evaluation of ophthalmologic
      inflammatory entities; finally, they discuss in detail several inflammatory
      conditions that affect the nervous system and the eye, emphasizing the features
      that should alert neurologists to initiate ophthalmologic evaluation. The
      conditions discussed include multiple sclerosis, neuromyelitis optica, chronic
      relapsing inflammatory optic neuropathy, Susac syndrome, Cogan syndrome, acute
      posterior multifocal placoid pigment epitheliopathy, Vogt-Koyanagi-Harada
      disease, Behcet disease, sarcoidosis, systemic lupus erythematosus,
      granulomatosis with polyangiitis (Wegener granulomatosis), polyarteritis nodosa,
      giant cell arteritis, IgG4-related disease, and Sjogren syndrome. 

PMID- 25369442
TI  - A neurologist's guide to safe use of immunomodulatory therapies.
AB  - Increased understanding of the pathogenesis of immune-mediated neurologic
      conditions with concomitant development of new therapeutic agents modulating
      various aspects of the immune system has resulted in the use of innovative
      therapies in the treatment of these diseases. These novel immunomodulatory
      therapeutic regimens also augment the potential for complications, including
      severe adverse effects.In this review, the authors address practical issues
      regarding management of patients with neuroimmunological conditions treated with
      immunomodulatory therapies, including glucocorticoids, methotrexate,
      azathioprine, mycophenolate, cyclophosphamide, rituximab, tumor necrosis factor
      alpha inhibitors, and intravenous immunoglobulins. Particular focus is placed on
      their infectious and noninfectious adverse effects, contraindications, safety
      monitoring, risk surveillance, and preventive strategies in clinical practice. 

PMID- 25369444
TI  - Inhibition of inflammation mediates the protective effect of atorvastatin reload
      in patients with coronary artery disease undergoing noncardiac emergency surgery.
AB  - OBJECTIVES: This study aimed to (a) investigate whether atorvastatin reload
      protects against acute heart failure (AHF) in patients with stable coronary
      artery disease (CAD) undergoing noncardiac emergency surgery and decreases the
      incidence of major adverse cardiac events (MACE) during hospitalization and (b)
      elucidate its possible mechanism of action. MATERIALS AND METHODS: In total, 500
      patients with stable CAD before noncardiac emergency surgery were randomized
      either to the atorvastatin reload or to the placebo group. All patients received
      atorvastatin treatment postoperatively. The primary end point was the incidence
      of AHF during hospitalization, and the secondary end point was the incidence of
      MACE during hospitalization. Preoperative and 72 h postoperative changes in high
      sensitivity C-reactive protein and interleukin-6 levels were compared between the
      two groups. RESULTS: AHF during hospitalization occurred in 5.2% of patients in
      the atorvastatin reload group and 11.2% in the placebo group (P=0.0225). MACE
      during hospitalization occurred in 2.4% of patients in the atorvastatin reload
      group and 8.0% in the placebo group (P=0.0088). According to multivariable
      analysis, atorvastatin reload conferred a 50% reduction in the risk of AHF during
      hospitalization (odds ratio, 0.50; 95% confidence interval, 0.2-0.8; P=0.005).
      The median decrease in the high-sensitivity C-reactive protein and interleukin-6
      levels was significantly greater in the atorvastatin reload group (P<0.001).
      CONCLUSION: Atorvastatin reload may improve the clinical outcome of patients with
      stable CAD undergoing noncardiac emergency surgery by decreasing the incidence of
      AHF and MACE during hospitalization. The mechanism of this protective effect may
      involve inhibition of inflammation.

PMID- 25369441
TI  - Neuronal surface antibody-mediated autoimmune encephalitis.
AB  - In the past few years, many autoimmune encephalitides have been identified, with
      specific clinical syndromes and associated antibodies against neuronal surface
      antigens. There is compelling evidence that many of these antibodies are
      pathogenic and most of these encephalitides are highly responsive to
      immunotherapies. The clinical spectra of some of these antibody-mediated
      syndromes, especially those reported in only a few patients, are evolving.
      Others, such as anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, are well
      characterized. Diagnosis involves recognizing the specific syndromes and
      identifying the antibody in a patient's cerebrospinal fluid (CSF) and/or serum.
      These syndromes are associated with variable abnormalities in CSF, magnetic
      resonance imaging, and electroencephalography. Treatment is often
      multidisciplinary and should be focused upon neutralizing the effects of
      antibodies and eliminating their source. Overlapping disorders have been noted,
      with some patients having more than one neurologic autoimmune disease. In other
      patients, viral infections such as herpes simplex virus encephalitis trigger
      robust antineuronal autoimmune responses. 

PMID- 25369445
TI  - Hydrated Excess Protons Can Create Their Own Water Wires.
AB  - Grotthuss shuttling of an excess proton charge defect through hydrogen bonded
      water networks has long been the focus of theoretical and experimental studies.
      In this work we show that there is a related process in which water molecules
      move ("shuttle") through a hydrated excess proton charge defect in order to wet
      the path ahead for subsequent proton charge migration. This process is
      illustrated through reactive molecular dynamics simulations of proton transport
      through a hydrophobic nanotube, which penetrates through a hydrophobic region.
      Surprisingly, before the proton enters the nanotube, it starts "shooting" water
      molecules into the otherwise dry space via Grotthuss shuttling, effectively
      creating its own water wire where none existed before. As the proton enters the
      nanotube (by 2-3 A), it completes the solvation process, transitioning the
      nanotube to the fully wet state. By contrast, other monatomic cations (e.g.,
      K(+)) have just the opposite effect, by blocking the wetting process and making
      the nanotube even drier. As the dry nanotube gradually becomes wet when the
      proton charge defect enters it, the free energy barrier of proton permeation
      through the tube via Grotthuss shuttling drops significantly. This finding
      suggests that an important wetting mechanism may influence proton translocation
      in biological systems, i.e., one in which protons "create" their own water
      structures (water "wires") in hydrophobic spaces (e.g., protein pores) before
      migrating through them. An existing water wire, e.g., one seen in an X-ray
      crystal structure or MD simulations without an explicit excess proton, is
      therefore not a requirement for protons to transport through hydrophobic spaces. 

PMID- 25369447
TI  - "Nothing special, everything is maamuli": socio-cultural and family practices
      influencing the perinatal period in urban India.
AB  - BACKGROUND: Globally, India contributes the largest share in sheer numbers to the
      burden of maternal and infant under-nutrition, morbidity and mortality. A major
      gap in our knowledge is how socio-cultural practices and beliefs influence the
      perinatal period and thus perinatal outcomes, particularly in the rapidly growing
      urban setting. METHODS AND FINDINGS: Using data from a qualitative study in urban
      south India, including in-depth interviews with 36 women who had recently been
      through childbirth as well as observations of family life and clinic encounters,
      we explored the territory of familial, cultural and traditional practices and
      beliefs influencing women and their families through pregnancy, childbirth and
      infancy. We found that while there were some similarities in cultural practices
      to those described before in studies from low resource village settings, there
      are changing practices and ideas. Fertility concerns dominate women's experience
      of married life; notions of gender preference and ideal family size are changing
      rapidly in response to the urban context; however inter-generational family
      pressures are still considerable. While a rich repertoire of cultural practices
      persists throughout the perinatal continuum, their existence is normalised and
      even underplayed. In terms of diet and nutrition, traditional messages including
      notions of 'hot' and 'cold' foods, are stronger than health messages; however
      breastfeeding is the cultural norm and the practice of delayed breastfeeding
      appears to be disappearing in this urban setting. Marriage, pregnancy and
      childbirth are so much part of the norm for women, that there is little
      expectation of individual choice in any of these major life events. CONCLUSIONS:
      A greater understanding is needed of the dynamic factors shaping the perinatal
      period in urban India, including an acknowledgment of the health promoting as
      well as potentially harmful cultural practices and the critical role of the
      family. This will help plan culturally appropriate integrated perinatal health
      care.

PMID- 25369448
TI  - Regenerative endodontic treatment of an immature tooth with a necrotic pulp and
      apical periodontitis using platelet-rich plasma (PRP) and mineral trioxide
      aggregate (MTA): a case report.
AB  - AIM: To report the successful clinical and radiographic outcome of a regenerative
      endodontic treatment. SUMMARY: A 16-year-old male patient presented with a
      discoloured, maxillary left lateral incisor with a necrotic pulp. Radiographic
      examination revealed an incompletely developed root with an open apex. Under
      local anaesthesia and rubber dam isolation, an access cavity was prepared and the
      necrotic pulpal remnants were removed. The canal was disinfected without
      mechanical instrumentation with 5.25% NaOCl solution and dried with sterile paper
      points. A triple antibiotic (metronidazole, ciprofloxacin and minocycline) mixed
      with distilled water was packed in the canal and left for 28 days. Ten
      millimetres of whole blood was drawn by venipuncture from the patients
      antecubital vein for preparation of platelet-rich plasma (PRP). After removal of
      the antibiotic mixture, the PRP was injected into the canal space up to the
      cementoenamel junction level. Three millimetres of white MTA was placed directly
      over the PRP clot. Two days later, the tooth was restored with permanent filling
      materials. The patient was recalled for 3, 6, 12, 24 and 36 months
      clinical/radiographic follow-up. A 3-year follow-up radiograph revealed
      resolution of the periapical lesion, increased thickening of the root walls,
      further root development and continued apical closure of the root apex. The tooth
      was not responsive to cold tests; however, sensitivity tests with an electric
      pulp tester (EPT) elicited a delayed positive response. KEY LEARNING POINTS:
      Regeneration is a viable treatment modality that allows continued root
      development of immature teeth with open apices and necrotic pulps. Platelet-rich
      plasma appears to be a suitable scaffold for regeneration of vital tissues in
      teeth with a necrotic pulps and an associated periapical lesion. Regenerative
      endodontic procedures may offer an effective treatment option to save teeth with
      compromised structural integrity.

PMID- 25369449
TI  - High-risk coronary plaque at coronary CT angiography is associated with
      nonalcoholic fatty liver disease, independent of coronary plaque and stenosis
      burden: results from the ROMICAT II trial.
AB  - PURPOSE: To determine the association between nonalcoholic fatty liver disease
      (NAFLD) and the presence of high-risk coronary atherosclerotic plaque as assessed
      with coronary computed tomographic (CT) angiography. MATERIALS AND METHODS: This
      study was approved by the local ethics committees; informed consent was obtained.
      Patients randomized to the coronary CT angiography arm of the Rule Out Myocardial
      Infarction using Computer Assisted Tomography, or ROMICAT, II trial who underwent
      both nonenhanced CT to assess calcium score and contrast material-enhanced
      coronary CT angiography were included. Readers assessed coronary CT angiography
      images for the presence of coronary plaque, significant stenosis (>=50%), and
      high-risk plaque features (positive remodeling, CT attenuation < 30 HU, napkin
      ring sign, spotty calcium). NAFLD was defined as hepatic steatosis at nonenhanced
      CT (liver minus spleen CT attenuation < 1 HU) without evidence of clinical liver
      disease, liver cirrhosis, or alcohol abuse. To determine the association between
      high-risk plaque and NAFLD, univariable and multivariable logistic regression
      analyses were performed, with high-risk plaque as a dependent variable and NAFLD,
      traditional risk factors, and extent of coronary atherosclerosis as independent
      variables. RESULTS: Overall, 182 (40.9%) of 445 patients had CT evidence of
      NAFLD. High-risk plaque was more frequent in patients with NAFLD than in patients
      without NAFLD (59.3% vs 19.0%, respectively; P < .001). The association between
      NAFLD and high-risk plaque (odds ratio, 2.13; 95% confidence interval: 1.18,
      3.85) persisted after adjusting for the extent and severity of coronary
      atherosclerosis and traditional risk factors. CONCLUSION: NAFLD is associated
      with advanced high-risk coronary plaque, independent of traditional
      cardiovascular risk factors and the extent and severity of coronary artery
      disease.

PMID- 25369450
TI  - A metabolic profiling strategy for the dissection of plant defense against fungal
      pathogens.
AB  - Here we present a metabolic profiling strategy employing direct infusion Orbitrap
      mass spectrometry (MS) and gas chromatography-mass spectrometry (GC/MS) for the
      monitoring of soybean's (Glycine max L.) global metabolism regulation in response
      to Rhizoctonia solani infection in a time-course. Key elements in the approach
      are the construction of a comprehensive metabolite library for soybean, which
      accelerates the steps of metabolite identification and biological interpretation
      of results, and bioinformatics tools for the visualization and analysis of its
      metabolome. The study of metabolic networks revealed that infection results in
      the mobilization of carbohydrates, disturbance of the amino acid pool, and
      activation of isoflavonoid, alpha-linolenate, and phenylpropanoid biosynthetic
      pathways of the plant. Components of these pathways include phytoalexins,
      coumarins, flavonoids, signaling molecules, and hormones, many of which exhibit
      antioxidant properties and bioactivity helping the plant to counterattack the
      pathogen's invasion. Unraveling the biochemical mechanism operating during
      soybean-Rhizoctonia interaction, in addition to its significance towards the
      understanding of the plant's metabolism regulation under biotic stress, provides
      valuable insights with potential for applications in biotechnology, crop
      breeding, and agrochemical and food industries. 

PMID- 25369451
TI  - Subsequent HIV infection among men who have sex with men who used non
      occupational post-exposure prophylaxis at a Boston community health center: 1997
      2013.
AB  - Non-occupational post-exposure prophylaxis (NPEP) has been recommended to prevent
      HIV acquisition for nearly 20 years. However, limited behavioral and clinical
      outcome data exist after men who have sex with men (MSM) present for NPEP. We
      reviewed the electronic medical records of HIV-uninfected adults who presented
      for NPEP at a large community health center in Boston between July, 1997 and
      August, 2013. Data from 894 patients were analyzed, 88.1% of whom were MSM.
      Consensual unprotected sex was the most common reason for NPEP visits among MSM
      (64.2%), followed by condom failure (30.6%). The HIV serostatus of the partner
      was unknown for 64.4% of the MSM, positive with unknown treatment status for
      18.1%, positive and not on treatment for 4.1%, and positive and on treatment for
      13.4%. Thirty-nine patients subsequently became HIV-infected (4.4%), all of whom
      were MSM. The MSM-specific HIV incidence after NPEP use was 2.2 cases per 100
      person-years. Incident HIV infection was associated with younger age (AHR=0.94;
      p=0.003), being Latino (AHR=2.44; p=0.044), and/or being African American
      (AHR=3.43; p=0.046). Repeated NPEP use was not associated with incident HIV
      infection (AHR=0.67; p=0.26). Younger MSM of color who access NPEP, in
      particular, may benefit from early HIV risk-reduction and pre-exposure
      prophylaxis counseling.

PMID- 25369452
TI  - Effect of peer counselling by mother support groups on infant and young child
      feeding practices: the Lalitpur experience.
AB  - OBJECTIVE: Our primary objective was to evaluate the effect of peer counselling
      by mother support groups (MSG's) in improving the infant and young child feeding
      (IYCF) practices in the community. METHODS: We conducted this repeated-measure
      before and after study in the Lalitpur district of Uttar Pradesh, India between
      2006 and 2011. We assessed the IYCF practices before and after creating MSG's
      within the community. The feeding practices were reassessed at two time points-2
      (T1) and 5 years (T2) after the intervention and compared with that of the pre
      intervention phase (T0). RESULTS: The total population covered by the project
      from the time of its initiation was 105000. A total of 425 (T0), 480 (T1) and 521
      (T2) mother infant pairs were selected from this population. There was
      significant improvement in the following IYCF practices in the community
      (represented as %; adjOR (95% CI, p) such as initiation of breast feeding within
      1 hour at both T1 (71% vs. 11%); 19.6 (13.6, 28.2, p =  <0.0001)and T2 (62% vs.
      11%); 13.3 (9.4, 18.9, p =  <0.0001); use of prelacteal feeds at both T1 (67% vs.
      15%); 12.6 (CI: 9.0, 17.6, p<0.0001) and T2 (67% vs. 5%); 44.4 (28.8, 68.4, p =
      <0.0001); rates of exclusive breast feeding for 6 months at both T1 (50% vs. 7%);
      13.6 (7.6, 25.0, p =  <0.0001) and T2 (60% vs. 7%); 20.5 (11.3, 37.2, p = 
      <0.0001); initiation of complementary feeding at T1 (85% vs. 54%); 5.6 (3.6, 8.7,
      p =  <0.0001) and T2 (96% vs. 54%); 22.9 (11.8, 44.1, p =  <0.0001) and
      complementary feeding along with continued breast feeding at both T1 (36% vs.
      4.5%); 6 (1.15, 31.4, p = 0.033) and T2 (42% vs. 4.5%); 8.06 (1.96, 49.1, p =
      0.005) as compared to pre-intervention period (T0) after adjusting for important
      social and demographic variables. CONCLUSIONS: Peer counseling by MSG's improved
      the IYCF practices in the district and could be sustained.

PMID- 25369453
TI  - Exogenous addition of arachidonic acid to the culture media enhances the
      functionality of dendritic cells for their possible use in cancer immunotherapy.
AB  - The development of dendritic cell based vaccines is a promising approach in
      cancer immunotherapy. For their successful use in the clinics, the propagation
      and functionality of DCs is crucial. We earlier established a two-step method for
      the large scale generation of DCs from umbilical cord blood derived MNCs/CD34(+)
      cells. This work aims at improving their functionality based on the following
      observations: in vitro generated DCs can be less efficient in migration and other
      functional activities due to lower eicosanoid levels. The production of
      eicosanoids from Arachidonic Acid (AA) can be hampered due to suppression of the
      enzyme phospholipase A2 by IL-4, an essential cytokine required for the
      differentiation of DCs. We hypothesized that exogenous addition of AA to the
      culture media during DC generation may result in DCs with improved functionality.
      DCs were generated with and without AA. The two DC sets were compared by
      phenotypic analysis, morphology and functional assays like antigen uptake, MLR,
      CTL assay and in vitro and in vivo migration. Though there were no differences
      between the two types of DCs in terms of morphology, phenotype and antigen
      uptake, AA(+) DCs exhibited an enhanced in vitro and in vivo migration, T cell
      stimulatory capacity, CTL activity and significantly higher transcript levels of
      COX-2. AA(+) DCs also show a favorable Th1 cytokine profile than AA- DCs. Thus
      addition of AA to the culture media is skewing the DCs towards the secretion of
      more IL-12 and less of IL-10 along with the restoration of eicosanoids levels in
      a COX-2 mediated pathway thereby enhancing the functionality of these cells to be
      used as a potent cellular vaccine. Taken together, these findings will be helpful
      in the better contriving of DC based vaccines for cancer immunotherapy.

PMID- 25369454
TI  - Allele frequencies of variants in ultra conserved elements identify selective
      pressure on transcription factor binding.
AB  - Ultra-conserved genes or elements (UCGs/UCEs) in the human genome are extreme
      examples of conservation. We characterized natural variations in 2884 UCEs and
      UCGs in two distinct populations; Singaporean Chinese (n = 280) and Italian (n =
      501) by using a pooled sample, targeted capture, sequencing approach. We
      identify, with high confidence, in these regions the abundance of rare SNVs
      (MAF<0.5%) of which 75% is not present in dbSNP137. UCEs association studies for
      complex human traits can use this information to model expected background
      variation and thus necessary power for association studies. By combining our data
      with 1000 Genome Project data, we show in three independent datasets that
      prevalent UCE variants (MAF>5%) are more often found in relatively less-conserved
      nucleotides within UCEs, compared to rare variants. Moreover, prevalent variants
      are less likely to overlap transcription factor binding site. Using SNPfold we
      found no significant influence of RNA secondary structure on UCE conservation.
      All together, these results suggest UCEs are not under selective pressure as a
      stretch of DNA but are under differential evolutionary pressure on the single
      nucleotide level.

PMID- 25369455
TI  - Access to diagnostic tests and essential medicines for cardiovascular diseases
      and diabetes care: cost, availability and affordability in the West Region of
      Cameroon.
AB  - OBJECTIVE: To assess the availability and affordability of medicines and routine
      tests for cardiovascular disease (CVD) and diabetes in the West region of
      Cameroon, a low-income setting. METHODS: A survey was conducted on the
      availability and cost of twelve routine tests and twenty medicines for CVD and
      diabetes in eight health districts (four urban and four rural) covering over 60%
      of the population of the region (1.8 million). We analyzed the percentage of
      tests and medicines available, the median price against the international
      reference price (median price ratio) for the medicines, and affordability in
      terms of the number of days' wages it would cost the lowest-paid unskilled
      government worker for initial investigation tests and procurement for one month
      of treatment. RESULTS: The availability of tests varied between 10% for the ECG
      to 100% for the fasting blood sugar. The average cost for the initial
      investigation using the minimum tests cost 29.76 days' wages. The availability of
      medicines varied from 36.4% to 59.1% in urban and from 9.1% to 50% in rural
      settings. Only metformin and benzathine-benzylpenicilline had a median price
      ratio of <= 1.5, with statins being largely unaffordable (at least 30.51 days'
      wages). One month of combination treatment for coronary heart disease costs at
      least 40.87 days' wages. CONCLUSION: The investigation and management of patients
      with medium-to-high cardiovascular risk remains largely unavailable and
      unaffordable in this setting. An effective non-communicable disease program
      should lay emphasis on primary prevention, and improve affordable access to
      essential medicines in public outlets.

PMID- 25369456
TI  - L-histidine inhibits biofilm formation and FLO11-associated phenotypes in
      Saccharomyces cerevisiae flor yeasts.
AB  - Flor yeasts of Saccharomyces cerevisiae have an innate diversity of Flo11p which
      codes for a highly hydrophobic and anionic cell-wall glycoprotein with a
      fundamental role in biofilm formation. In this study, 380 nitrogen compounds were
      administered to three S. cerevisiae flor strains handling Flo11p alleles with
      different expression levels. S. cerevisiae strain S288c was used as the reference
      strain as it cannot produce Flo11p. The flor strains generally metabolized amino
      acids and dipeptides as the sole nitrogen source, although with some exceptions
      regarding L-histidine and histidine containing dipeptides. L-histidine completely
      inhibited growth and its effect on viability was inversely related to Flo11p
      expression. Accordingly, L-histidine did not affect the viability of the
      Deltaflo11 and S288c strains. Also, L-histidine dramatically decreased air-liquid
      biofilm formation and adhesion to polystyrene of the flor yeasts with no effect
      on the transcription level of the Flo11p gene. Moreover, L-histidine modified the
      chitin and glycans content on the cell-wall of flor yeasts. These findings reveal
      a novel biological activity of L-histidine in controlling the multicellular
      behavior of yeasts [corrected].

PMID- 25369457
TI  - Association between lifestyle factors and quality-adjusted life years in the EPIC
      NL cohort.
AB  - The aim of our study was to relate four modifiable lifestyle factors (smoking
      status, body mass index, physical activity and diet) to health expectancy, using
      quality-adjusted life years (QALYs) in a prospective cohort study. Data of the
      prospective EPIC-NL study were used, including 33,066 healthy men and women aged
      20-70 years at baseline (1993-7), followed until 31-12-2007 for occurrence of
      disease and death. Smoking status, body mass index, physical activity and
      adherence to a Mediterranean-style diet (excluding alcohol) were investigated
      separately and combined into a healthy lifestyle score, ranging from 0 to 4.
      QALYs were used as summary measure of healthy life expectancy, combining a
      person's life expectancy with a weight for quality of life when having a chronic
      disease. For lifestyle factors analyzed separately the number of years living
      longer in good health varied from 0.12 year to 0.84 year, after adjusting for
      covariates. A combination of the four lifestyle factors was positively associated
      with higher QALYs (P-trend <0.0001). A healthy lifestyle score of 4 compared to a
      score of 0 was associated with almost a 2 years longer life in good health (1.75
      QALYs [95% CI 1.37, 2.14]). 

PMID- 25369460
TI  - A qualitative study of successful adolescent and young adult weight losers:
      implications for weight control intervention.
AB  - BACKGROUND: Our study aims to provide an in-depth analysis of behavioral
      strategies, psychological factors, and social contributors to adolescent weight
      loss and weight loss maintenance among participants in the Adolescent Weight
      Control Registry (AWCR). METHODS: Qualitative analyses were conducted using semi
      structured interview data from 40 participants from the AWCR who successfully
      lost >=10 lbs and maintained their weight loss for at least one year. RESULTS: In
      contrast to existing literature, our findings suggest that primary motivating
      factors for adolescent weight loss may be intrinsic (e.g., desire for better
      health, desire to improve self-worth) rather than extrinsic. In addition, life
      transitions (e.g., transition to high school) were identified as substantial
      motivators for weight-related behavior change. Peer and parental encouragement
      and instrumental support were widely endorsed as central to success. The most
      commonly endorsed weight loss maintenance strategies included attending to
      dietary intake and physical activity levels, and making self-corrections when
      necessary. CONCLUSIONS: Results from this study highlight considerations for
      future adolescent weight control treatment development.

PMID- 25369459
TI  - Restricting or banning alcohol advertising to reduce alcohol consumption in
      adults and adolescents.
AB  - BACKGROUND: Alcohol is estimated to be the fifth leading risk factor for global
      disability-adjusted life years. Restricting or banning alcohol advertising may
      reduce exposure to the risk posed by alcohol at the individual and general
      population level. To date, no systematic review has evaluated the effectiveness,
      possible harms and cost-effectiveness of this intervention. OBJECTIVES: To
      evaluate the benefits, harms and costs of restricting or banning the advertising
      of alcohol, via any format, compared with no restrictions or counter-advertising,
      on alcohol consumption in adults and adolescents. SEARCH METHODS: We searched the
      Cochrane Drugs and Alcohol Group Specialised Register (May 2014); CENTRAL (Issue
      5, 2014); MEDLINE (1966 to 28 May 2014); EMBASE (1974 to 28 May 2014); PsychINFO
      (June 2013); and five alcohol and marketing databases in October 2013. We also
      searched seven conference databases and www.clinicaltrials.gov and
      http://apps.who.int/trialsearch/ in October 2013. We checked the reference lists
      of all studies identified and those of relevant systematic reviews or guidelines,
      and contacted researchers, policymakers and other experts in the field for
      published or unpublished data, regardless of language. SELECTION CRITERIA: We
      included randomised controlled trials (RCTs), controlled clinical trials,
      prospective and retrospective cohort studies, controlled before-and-after studies
      and interrupted time series (ITS) studies that evaluated the restriction or
      banning of alcohol advertising via any format including advertising in the press,
      on the television, radio, or internet, via billboards, social media or product
      placement in films. The data could be at the individual (adults or adolescent) or
      population level. DATA COLLECTION AND ANALYSIS: We used the standard
      methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS:
      We included one small RCT (80 male student participants conducted in the
      Netherlands and published in 2009) and three ITS studies (general population
      studies in Canadian provinces conducted in the 1970s and 80s).The RCT found that
      young men exposed to movies with a low-alcohol content drank less than men
      exposed to movies with a high-alcohol content (mean difference (MD) -0.65 drinks;
      95% CI -1.2, -0.07; p value = 0.03, very-low-quality evidence). Young men exposed
      to commercials with a neutral content compared with those exposed to commercials
      for alcohol drank less (MD -0.73 drinks; 95% CI -1.30, -0.16; p value = 0.01,
      very-low-quality evidence). Outcomes were assessed immediately after the end of
      the intervention (lasting 1.5 hours), so no follow-up data were available. Using
      the Grading of Recommendations Assessment, Development and Evaluation approach,
      the quality of the evidence was rated as very low due to a serious risk of bias,
      serious indirectness of the included population and serious level of
      imprecision.Two of the ITS studies evaluated the implementation of an advertising
      ban and one study evaluated the lifting of such a ban. Each of the three ITS
      studies evaluated a different type of ban (partial or full) compared with
      different degrees of restrictions or no restrictions during the control period.
      The results from the three ITS studies were inconsistent. A meta-analysis of the
      two studies that evaluated the implementation of a ban showed an overall mean non
      significant increase in beer consumption in the general population of 1.10%
      following the ban (95% CI -5.26, 7.47; p value = 0.43; I(2) = 83%, very-low
      quality evidence). This finding is consistent with an increase, no difference, or
      a decrease in alcohol consumption. In the study evaluating the lifting of a total
      ban on all forms of alcohol advertising to a partial ban on spirits advertising
      only, which utilised an Abrupt Auto-regressive Integrated Moving Average model,
      the volume of all forms of alcohol sales decreased by 11.11 kilolitres (95% CI 
      27.56, 5.34; p value = 0.19) per month after the ban was lifted. In this model,
      beer and wine sales increased per month by 14.89 kilolitres (95% CI 0.39, 29.39;
      p value = 0.04) and 1.15 kilolitres (95% CI -0.91, 3.21; p value = 0.27),
      respectively, and spirits sales decreased statistically significantly by 22.49
      kilolitres (95% CI -36.83, -8.15; p value = 0.002). Using the GRADE approach, the
      evidence from the ITS studies was rated as very low due to a high risk of bias
      arising from a lack of randomisation and imprecision in the results.No other
      prespecified outcomes (including economic loss or hardship due to decreased
      alcohol sales) were addressed in the included studies and no adverse effects were
      reported in any of the studies. None of the studies were funded by the alcohol or
      advertising industries. AUTHORS' CONCLUSIONS: There is a lack of robust evidence
      for or against recommending the implementation of alcohol advertising
      restrictions. Advertising restrictions should be implemented within a high
      quality, well-monitored research programme to ensure the evaluation over time of
      all relevant outcomes in order to build the evidence base.

PMID- 25369461
TI  - Transition metal-mediated C?O and C?C bond-forming reactions: a regioselective
      strategy for the synthesis of imidazo[1,2-a]pyridines and imidazo[1,2
      a]pyrazines.
AB  - A novel and convenient transformation for the regiospecific synthesis of
      functionalized imidazo[1,2-a]pyridine aldehydes/ketones and 3-vinyl imidazo[1,2
      a]pyridines has been developed via copper(I)- and palladium(II)-catalyzed
      cyclization. The one-pot reaction proceeds smoothly with commercially available
      catalysts and affords the products in moderate to good yields. It represents an
      efficient approach for the formation of C-N, C?O, and C?C bonds under mild
      conditions. 

PMID- 25369458
TI  - Toward primary prevention of asthma. Reviewing the evidence for early-life
      respiratory viral infections as modifiable risk factors to prevent childhood
      asthma.
AB  - A first step in primary disease prevention is identifying common, modifiable risk
      factors that contribute to a significant proportion of disease development.
      Infant respiratory viral infection and childhood asthma are the most common acute
      and chronic diseases of childhood, respectively. Common clinical features and
      links between these diseases have long been recognized, with early-life
      respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract
      infections (LRTIs) being strongly associated with increased asthma risk. However,
      there has long been debate over the role of these respiratory viruses in asthma
      inception. In this article, we systematically review the evidence linking early
      life RSV and RV LRTIs with asthma inception and whether they could therefore be
      targets for primary prevention efforts. 

PMID- 25369463
TI  - Tyrosine 110 plays a critical role in regulating the allosteric inhibition of
      Campylobacter jejuni dihydrodipicolinate synthase by lysine.
AB  - Dihydrodipicolinate synthase (DHDPS), an enzyme found in most bacteria and
      plants, controls a critical step in the biosynthesis of l-lysine and meso
      diaminopimelate, necessary components for bacterial cell wall biosynthesis. DHDPS
      catalyzes the condensation of pyruvate and (S)-aspartate-beta-semialdehyde,
      forming an unstable product that is dehydrated to dihydrodipicolinate. The
      tetrameric enzyme is allosterically inhibited by l-lysine, and a better
      understanding of the allosteric inhibition mechanism is necessary for the design
      of potent antibacterial therapeutics. Here we describe the high-resolution
      crystal structures of DHDPS from Campylobacter jejuni with and without its
      inhibitor bound to the allosteric sites. These structures reveal a role for Y110
      in the regulation of the allosteric inhibition by lysine. Mutation of Y110 to
      phenylalanine results in insensitivity to lysine inhibition, although the mutant
      crystal structure reveals that lysine does bind in the allosteric site.
      Comparison of the lysine-bound Y110F structure with wild-type structures reveals
      that key structural changes due to lysine binding are absent in this mutant. 

PMID- 25369462
TI  - The role of apolipoprotein E as a risk factor for an earlier age at onset for
      Machado-Joseph disease is doubtful.
AB  - Machado-Joseph disease (MJD) is an inherited neurodegenerative disease caused by
      an expanded CAG repeat in the ATXN3 gene. Although the principal genetic
      determinant of the age at onset (AAO) is the length of the expanded CAG repeat,
      the additional genetic contribution of MJD toward the AAO has mostly not yet been
      clarified. It was recently suggested in two independent studies that
      apolipoprotein E (APOE) might be associated with AAO variability in MJD patients.
      To identify the potential modifier effect of APOE polymorphisms on the AAO of MJD
      patients, 403 patients with MJD (confirmed by molecular tests) from eastern and
      southeastern China were enrolled in the present study. CAG repeats in the ATXN3
      and APOE polymorphisms were genotyped. Data were analyzed using a statistical
      package. No contribution of APOE polymorphisms to the variance in disease onset
      was observed using ANCOVA (F = 0.183, P = 0.947). However, significant effects on
      the AAO of MJD were found for the normal ATXN3 allele and for the interaction of
      mutant and normal ATXN3 alleles in a multiple linear regression model (P = 0.043
      and P = 0.035, respectively). Our study does not support a role for APOE as a
      genetic modifier of the AAO of MJD. Additionally, our study presents evidence
      that the normal ATXN3 allele and its interaction with mutant alleles contribute
      toward AAO variance in MJD patients.

PMID- 25369464
TI  - DNA synthesis in periportal and perivenous hepatocytes of intact and
      hepatectomized young mice.
AB  - DNA synthesis of hepatocytes in two areas of Intact and Hepatectomized young mice
      liver along a circadian period was studied. DNA synthesis was significantly
      different at all analyzed time points in Intact and Hepatectomized animals.
      Differences between periportal and perivenous hepatocytes were found in
      hepatectomized animals at 04/42 and 08/46 hr of day/hour post-hepatectomy. DNAs
      peak in periportal hepatocytes regenerating liver occurs 4 hr earlier than in
      perivenous hepatocytes, probably reflecting their shorter G1 phase. Besides,
      daily mean values of regenerating livers were higher than those observed in
      Intact animals, as a consequence of surgical removal. 

PMID- 25369466
TI  - Total synthesis of the macrocyclic N-Methyl enamides palmyrolide A and 2S
      sanctolide A.
AB  - Full details of the total syntheses of the initially reported and revised
      structures of the neuroprotective agent palmyrolide A are reported. The key
      macrocyclization step was achieved using a sequential ring-closing
      metathesis/olefin isomerization reaction. Furthermore, the total synthesis of the
      related macrolide (2S)-sanctolide A is reported. The synthesis used key elements
      from the synthesis of palmyrolide A, including the RCM/olefin isomerization
      sequence. The synthetic work described herein serves to facilitate the assignment
      of stereochemistry of the natural product sanctolide A and demonstrates the
      utility of this approach for the synthesis of macrocyclic tertiary enamide
      natural products. 

PMID- 25369465
TI  - Deficient grip force control in schizophrenia: behavioral and modeling evidence
      for altered motor inhibition and motor noise.
AB  - Whether upper limb sensorimotor control is affected in schizophrenia and how
      underlying pathological mechanisms may potentially intervene in these deficits is
      still being debated. We tested voluntary force control in schizophrenia patients
      and used a computational model in order to elucidate potential cerebral
      mechanisms underlying sensorimotor deficits in schizophrenia. A visuomotor grip
      force-tracking task was performed by 17 medicated and 6 non-medicated patients
      with schizophrenia (DSM-IV) and by 15 healthy controls. Target forces in the ramp
      hold-and-release paradigm were set to 5 N and to 10% maximal voluntary grip
      force. Force trajectory was analyzed by performance measures and Principal
      Component Analysis (PCA). A computational model incorporating neural control
      signals was used to replicate the empirically observed motor behavior and to
      explore underlying neural mechanisms. Grip task performance was significantly
      lower in medicated and non-medicated schizophrenia patients compared to controls.
      Three behavioral variables were significantly higher in both patient groups:
      tracking error (by 50%), coefficient of variation of force (by 57%) and duration
      of force release (up by 37%). Behavioral performance did not differ between
      patient groups. Computational simulation successfully replicated these findings
      and predicted that decreased motor inhibition, together with an increased signal
      dependent motor noise, are sufficient to explain the observed motor deficits in
      patients. PCA also suggested altered motor inhibition as a key factor
      differentiating patients from control subjects: the principal component
      representing inhibition correlated with clinical severity. These findings show
      that schizophrenia affects voluntary sensorimotor control of the hand independent
      of medication, and suggest that reduced motor inhibition and increased signal
      dependent motor noise likely reflect key pathological mechanisms of the
      sensorimotor deficit.

PMID- 25369467
TI  - Lithiation of SiO2 in Li-ion batteries: in situ transmission electron microscopy
      experiments and theoretical studies.
AB  - Surface passivation has become a routine strategy of design to mitigate the
      chemomechanical degradation of high-capacity electrodes by regulating the
      electrochemical process of lithiation and managing the associated deformation
      dynamics. Oxides are the prevalent materials used for surface coating. Lithiation
      of SiO2 leads to drastic changes in its electro-chemo-mechanical properties from
      an electronic insulator and a brittle material in its pure form to a conductor
      and a material sustainable of large deformation in the lithiated form. We
      synthesized SiO2-coated SiC nanowires that allow us to focus on the lithiation
      behavior of the sub-10 nm SiO2 thin coating. We systematically investigate the
      structural evolution, the electronic conduction and ionic transport properties,
      and the deformation pattern of lithiated SiO2 through coordinated in situ
      transmission electron microcopy experiments, first-principles computation, and
      continuum theories. We observe the stress-mediated reaction that induces
      inhomogeneous growth of SiO2. The results provide fundamental perspectives on the
      chemomechanical behaviors of oxides used in the surface coating of Li-ion
      technologies. 

PMID- 25369468
TI  - Biomarkers for monitoring pre-analytical quality variation of mRNA in blood
      samples.
AB  - There is an increasing need for proper quality control tools in the pre
      analytical phase of the molecular diagnostic workflow. The aim of the present
      study was to identify biomarkers for monitoring pre-analytical mRNA quality
      variations in two different types of blood collection tubes, K2EDTA (EDTA) tubes
      and PAXgene Blood RNA Tubes (PAXgene tubes). These tubes are extensively used
      both in the diagnostic setting as well as for research biobank samples. Blood
      specimens collected in the two different blood collection tubes were stored for
      varying times at different temperatures, and microarray analysis was performed on
      resultant extracted RNA. A large set of potential mRNA quality biomarkers for
      monitoring post-phlebotomy gene expression changes and mRNA degradation in blood
      was identified. qPCR assays for the potential biomarkers and a set of relevant
      reference genes were generated and used to pre-validate a sub-set of the selected
      biomarkers. The assay precision of the potential qPCR based biomarkers was
      determined, and a final validation of the selected quality biomarkers using the
      developed qPCR assays and blood samples from 60 healthy additional subjects was
      performed. In total, four mRNA quality biomarkers (USP32, LMNA, FOSB, TNRFSF10C)
      were successfully validated. We suggest here the use of these blood mRNA quality
      biomarkers for validating an experimental pre-analytical workflow. These
      biomarkers were further evaluated in the 2nd ring trial of the SPIDIA-RNA Program
      which demonstrated that these biomarkers can be used as quality control tools for
      mRNA analyses from blood samples. 

PMID- 25369469
TI  - AP2 suppresses osteoblast differentiation and mineralization through down
      regulation of Frizzled-1.
AB  - Transcription factor activating protein 2 (AP2) plays an important role in
      cellular differentiation. Although profound craniofacial and long bone
      developmental abnormalities have been observed in AP2-knockout mice, the
      molecular effects of AP2 on osteoblasts are poorly defined. We demonstrated that
      AP2 regulates the expression of human Frizzled 1 (FZD1), a co-receptor for the
      Wnt signalling pathway, in human osteoblast cell lines and primary bone marrow
      stromal cells (BMSCs). We also identified a putative AP2-binding site in the FZD1
      proximal promoter in silico and characterized this binding element further in
      Saos2 in vitro by ChIP, electrophoretic mobility shift and promoter reporter
      assays. The transcriptional repression of the FZD1 promoter by AP2 was confirmed
      in normal human fetal osteoblasts (hFOB). Furthermore, overexpression of AP2
      resulted in a significant reduction in both differentiation and mineralization of
      Saos2 cells. Knockdown of FZD1 expression before AP2 up-regulation diminished the
      AP2-dependent inhibition of Saos2 cell differentiation and mineralization.
      Similarly, overexpressing FZD1 before AP2 treatment in both Saos2 and BMSCs
      diminished the inhibitory effect of AP2 on osteoblast differentiation and
      mineralization. Taken together, these results demonstrate that AP2 is a negative
      regulator of osteoblast differentiation and mineralization, and its inhibitory
      effect may be mediated in part through down-regulation of FZD1 expression. 

PMID- 25369470
TI  - Astemizole arrests the proliferation of cancer cells by disrupting the EZH2-EED
      interaction of polycomb repressive complex 2.
AB  - Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and
      transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3),
      a process that necessitates the protein-protein interaction (PPI) between the
      catalytic subunit EZH2 and EED. Deregulated PRC2 is intimately involved in
      tumorigenesis and progression, making it an invaluable target for epigenetic
      cancer therapy. However, until now, there have been no reported small molecule
      compounds targeting the EZH2-EED interactions. In the present study, we
      identified astemizole, an FDA-approved drug, as a small molecule inhibitor of the
      EZH2-EED interaction of PRC2. The disruption of the EZH2-EED interaction by
      astemizole destabilizes the PRC2 complex and inhibits its methyltransferase
      activity in cancer cells. Multiple lines of evidence have demonstrated that
      astemizole arrests the proliferation of PRC2-driven lymphomas primarily by
      disabling the PRC2 complex. Our findings demonstrate the chemical tractability of
      the difficult PPI target by a small molecule compound, highlighting the
      therapeutic promise for PRC2-driven human cancers via targeted destruction of the
      EZH2-EED complex. 

PMID- 25369471
TI  - Effectiveness of ART and condom use for prevention of sexual HIV transmission in
      serodiscordant couples: a systematic review and meta-analysis.
AB  - BACKGROUND: Consistent and correct condom use and suppressive antiretroviral
      therapy for the infected partner are two of the primary strategies recommended
      for prevention of heterosexual HIV transmission in serodiscordant couples today.
      The applied effectiveness of treatment as a prevention strategy in China is still
      under investigation, and much less is known about its effects in the presence of
      other prevention strategies such as consistent condom use. METHODS: We conducted
      a systematic search in PubMed and three Chinese language databases to identify
      relevant articles for the estimation of relative effectiveness of a) consistent
      condom use and b) ART use by index partners for preventing HIV transmission in
      serodiscordant couples. We also estimated the prevention effectiveness of ART
      stratified by condom use level and the prevention effectiveness of consistent
      condom use stratified by ART use level. RESULTS: Pooled results from the eleven
      eligible studies found a pooled HIV seroconversion incidence of 0.92 cases per
      100 person years (PY) among HIV-negative spouses whose index partners were taking
      ART versus 2.45 cases per 100 PY in untreated couples. The IRR comparing
      seroconversion in couples where the index-partner was on ART versus not on ART
      was 0.47 (95%CI: 0.43, 0.52), while stratified by condom use, the IRR was
      0.33(0.17,0.64). The IRR comparing incidence in couples reporting "consistent
      condom use" versus those reporting otherwise was 0.02(95%CI:0.01,0.04), after
      stratified by ART use level, the IRR was 0.01(95%CI: 0.00, 0.06). CONCLUSIONS:
      ART use by index partners could reduce HIV transmission in serodiscordant
      couples, and the effectiveness of this prevention strategy could be further
      increased with consistent condom use.

PMID- 25369472
TI  - Gender disparities in latent tuberculosis infection in high-risk individuals: a
      cross-sectional study.
AB  - Male predominance in active tuberculosis (TB) is widely-reported globally. Gender
      inequalities in socio-cultural status are frequently regarded as contributing
      factors for disparities in sex in active TB. The disparities of sex in the
      prevalence of latent TB infection (LTBI) are less frequently investigated and
      deserve clarification. In this cross-sectional study conducted in a TB endemic
      area, we enrolled patients at high-risk for LTBI and progression from LTBI to
      active TB from 2011 to 2012. Diagnosis of LTBI was made by QuantiFERON-TB Gold In
      Tube (QFT-GIT). Differences in sex in terms of prevalence of LTBI and clinical
      predictors for LTBI were investigated. Associations among age, smoking status,
      and sex disparities in LTBI were also analyzed. A total of 1018 high-risk
      individuals with definite QFT-GIT results were included for analysis, including
      534 males and 484 females. The proportion of LTBI was significantly higher in
      males than in females (32.6% vs. 25.2%, p = 0.010). Differences in the proportion
      of LTBI between sexes were most prominent in older patients (age >= 55 years). In
      multivariate analysis, independent clinical factors associated with LTBI were age
      (p = 0.014), smoking (p = 0.048), and fibro-calcified lesions on chest radiogram
      (p = 0.009). Male sex was not an independent factor for LTBI (p = 0.88). When
      stratifying patients according to the smoking status, the proportion of LTBI
      remained comparable between sexes among smokers and non-smokers. In conclusion,
      although the proportion of LTBI is higher in men, there is no significant
      disparity in terms of sex in LTBI among high-risk individuals after adjusting for
      age, smoking status, and other clinical factors.

PMID- 25369473
TI  - Investigation of temperature induced mechanical changes in supported bilayers by
      variants of tapping mode atomic force microscopy.
AB  - Tapping mode atomic force microscopy (AFM) is an invaluable technique for
      examining topographical features of biological materials in solution, and there
      has been a growing interest in developing techniques to provide further
      compositional contrast and information concerning surface mechanical properties.
      Phase shifts, cantilever response at higher harmonic frequencies of the drive,
      and time-resolved tip/sample force reconstruction have all been shown to provide
      additional compositional contrast of surfaces, as compared to basic tapping mode
      AFM imaging. This study aimed to demonstrate the relative ability of these
      different imaging techniques to detect temperature induced changes in the elastic
      modulus of supported total brain lipid extract (TBLE) bilayer patches on mica. To
      aid in direct comparison between the different imaging techniques, all required
      data was obtained simultaneously while capturing traditional tapping mode AFM
      topography images. While all of the techniques were able to provide compositional
      contrast consistent with known temperature-induced changes in the bilayer patch,
      interpretation of the resulting contrast was not always straightforward. Phase
      imaging suffered from contrast inversion. Individual harmonics responded in a
      variety of ways to the temperature-induced changes in elastic modulus of the
      bilayer. The maximum tapping force (or peak force) associated with imaging the
      bilayer correctly reflected the changes in elastic modulus of the lipid bilayer.
      Importantly, as the required data can be obtained simultaneously, combining these
      different imaging techniques can lead to a more complete understanding of a
      sample's mechanical features.

PMID- 25369474
TI  - Changing gull diet in a changing world: a 150-year stable isotope (delta13C,
      delta15N) record from feathers collected in the Pacific Northwest of North
      America.
AB  - The world's oceans have undergone significant ecological changes following
      European colonial expansion and associated industrialization. Seabirds are useful
      indicators of marine food web structure and can be used to track multidecadal
      environmental change, potentially reflecting long-term human impacts. We used
      stable isotope (delta(13)C, delta(15)N) analysis of feathers from glaucous-winged
      gulls (Larus glaucescens) in a heavily disturbed region of the northeast Pacific
      to ask whether diets of this generalist forager changed in response to shifts in
      food availability over 150 years, and whether any detected change might explain
      long-term trends in gull abundance. Sampled feathers came from birds collected
      between 1860 and 2009 at nesting colonies in the Salish Sea, a transboundary
      marine system adjacent to Washington, USA and British Columbia, Canada. To
      determine whether temporal trends in stable isotope ratios might simply reflect
      changes to baseline environmental values, we also analysed muscle tissue from
      forage fishes collected in the same region over a multidecadal timeframe. Values
      of delta(13)C and delta(15)N declined since 1860 in both subadult and adult gulls
      (delta(13)C, ~ 2-60/00; delta(15)N, ~4-50/00), indicating that their diet has
      become less marine over time, and that birds now feed at a lower trophic level
      than previously. Conversely, forage fish delta(13)C and delta(15)N values showed
      no trends, supporting our conclusion that gull feather values were indicative of
      declines in marine food availability rather than of baseline environmental
      change. Gradual declines in feather isotope values are consistent with trends
      predicted had gulls consumed less fish over time, but were equivocal with respect
      to whether gulls had switched to a more garbage-based diet, or one comprising
      marine invertebrates. Nevertheless, our results suggest a long-term decrease in
      diet quality linked to declining fish abundance or other anthropogenic
      influences, and may help to explain regional population declines in this species
      and other piscivores.

PMID- 25369477
TI  - The lady in mauve: Lyonel Feininger.

PMID- 25369478
TI  - Recent suicides highlight need to address depression in medical students and
      residents.

PMID- 25369479
TI  - Rate of suicide increases in middle age: primary care key to suicide prevention.

PMID- 25369486
TI  - Hearing and vision care for older adults: sensing a need to update Medicare
      policy.

PMID- 25369487
TI  - A piece of my mind. In all of us.

PMID- 25369488
TI  - Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic
      melanoma: a randomized clinical trial.
AB  - IMPORTANCE: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade with
      ipilimumab prolongs survival in patients with metastatic melanoma. CTLA-4
      blockade and granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting
      tumor vaccine combinations demonstrate therapeutic synergy in preclinical models.
      A key unanswered question is whether systemic GM-CSF (sargramostim) enhances CTLA
      4 blockade. OBJECTIVE: To compare the effect of ipilimumab plus sargramostim vs
      ipilimumab alone on overall survival (OS) in patients with metastatic melanoma.
      DESIGN, SETTING, AND PARTICIPANTS: The Eastern Cooperative Oncology Group (ECOG)
      conducted a US-based phase 2 randomized clinical trial from December 28, 2010,
      until July 28, 2011, of patients (N = 245) with unresectable stage III or IV
      melanoma, at least 1 prior therapy, no central nervous system metastases, and
      ECOG performance status of 0 or 1. INTERVENTIONS: Patients were randomized to
      receive ipilimumab, 10 mg/kg, intravenously on day 1 plus sargramostim, 250 MUg
      subcutaneously, on days 1 to 14 of a 21-day cycle (n = 123) vs ipilimumab alone
      (n = 122). Ipilimumab treatment included induction for 4 cycles followed by
      maintenance every fourth cycle. MAIN OUTCOMES AND MEASURES: Primary end point:
      comparison of length of OS. Secondary end point: progression-free survival (PFS),
      response rate, safety, and tolerability. RESULTS: Median follow-up was 13.3
      months (range, 0.03-19.9). Median OS as of December 2012 for ipilimumab plus
      sargramostim was 17.5 months (95% CI, 14.9-not reached) vs 12.7 months (95% CI,
      10.0-not reached) for ipilimumab. The 1-year survival rate for ipilimumab plus
      sargramostim was 68.9% (95% CI, 60.6%-85.5%) compared to 52.9% (95% CI, 43.6%
      62.2%) for ipilimumab alone (stratified log-rank 1-sided P = .01; mortality
      hazard ratio 0.64 [1-sided 90% repeated CI, not applicable-0.90]). A planned
      interim analysis was conducted at 69.8% of expected events (104 observed with 149
      expected deaths). Planned interim analysis using the O'Brien-Fleming boundary was
      crossed for improvement in OS. There was no difference in PFS. Median PFS for
      ipilimumab plus sargramostim was 3.1 months (95% CI, 2.9-4.6) vs 3.1 months (95%
      CI, 2.9-4.0) for ipilimumab alone. Grade 3 to 5 adverse events occurred in 44.9%
      (95% CI; 35.8%-54.4%) of patients in the ipilimumab plus sargramostim group vs
      58.3% (95% CI, 49.0%-67.2%) of patients in the ipilimumab-alone group (2-sided P
      = .04). CONCLUSION AND RELEVANCE: Among patients with unresectable stage III or
      IV melanoma, treatment with ipilimumab plus sargramostim vs ipilimumab alone
      resulted in longer OS and lower toxicity, but no difference in PFS. These
      findings require confirmation in larger studies with longer follow-up. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01134614.

PMID- 25369489
TI  - Nonobstructive coronary artery disease and risk of myocardial infarction.
AB  - IMPORTANCE: Little is known about cardiac adverse events among patients with
      nonobstructive coronary artery disease (CAD). OBJECTIVE: To compare myocardial
      infarction (MI) and mortality rates between patients with nonobstructive CAD,
      obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective cohort study of all US veterans undergoing elective
      coronary angiography for CAD between October 2007 and September 2012 in the
      Veterans Affairs health care system. Patients with prior CAD events were
      excluded. EXPOSURES: Angiographic CAD extent, defined by degree (no apparent CAD:
      no stenosis >20%; nonobstructive CAD: >=1 stenosis >=20% but no stenosis >=70%;
      obstructive CAD: any stenosis >=70% or left main [LM] stenosis >=50%) and
      distribution (1, 2, or 3 vessel). MAIN OUTCOMES AND MEASURES: The primary outcome
      was 1-year hospitalization for nonfatal MI after the index angiography. Secondary
      outcomes included 1-year all-cause mortality and combined 1-year MI and
      mortality. RESULTS: Among 37,674 patients, 8384 patients (22.3%) had
      nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1
      year, 845 patients died and 385 were rehospitalized for MI. Among patients with
      no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and
      increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI,
      0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%-1.00%); 3
      vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel
      obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD,
      2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47%
      (n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with
      increasing CAD extent. Relative to patients with no apparent CAD, patients with 1
      vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI,
      0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel
      nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI,
      4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM
      obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated
      with increasing CAD extent, ranging from 1.38% among patients without apparent
      CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there
      was no significant association between 1- or 2-vessel nonobstructive CAD and
      mortality, but there were significant associations with mortality for 3-vessel
      nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9;
      95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3
      vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations
      were noted with the combined outcome. CONCLUSIONS AND RELEVANCE: In this cohort
      of patients undergoing elective coronary angiography, nonobstructive CAD,
      compared with no apparent CAD, was associated with a significantly greater 1-year
      risk of MI and all-cause mortality. These findings suggest clinical importance of
      nonobstructive CAD and warrant further investigation of interventions to improve
      outcomes among these patients.

PMID- 25369490
TI  - Behavioral treatment of obesity in patients encountered in primary care settings:
      a systematic review.
AB  - IMPORTANCE: In 2011, the Centers for Medicare & Medicaid Services (CMS) approved
      intensive behavioral weight loss counseling for approximately 14 face-to-face, 10
      to 15-minute sessions over 6 months for obese beneficiaries in primary care
      settings, when delivered by physicians and other CMS-defined primary care
      practitioners. OBJECTIVE: To conduct a systematic review of behavioral counseling
      for overweight and obese patients recruited from primary care, as delivered by
      primary care practitioners working alone or with trained interventionists (eg,
      medical assistants, registered dietitians), or by trained interventionists
      working independently. EVIDENCE REVIEW: We searched PubMed, CINAHL, and EMBASE
      for randomized controlled trials published between January 1980 and June 2014
      that recruited overweight and obese patients from primary care; provided
      behavioral counseling (ie, diet, exercise, and behavioral therapy) for at least 3
      months, with at least 6 months of postrandomization follow-up; included at least
      15 participants per treatment group and objectively measured weights; and had a
      comparator, an intention-to-treat analysis, and attrition of less than 30% at 1
      year or less than 40% at longer follow-up. FINDINGS: Review of 3304 abstracts
      yielded 12 trials, involving 3893 participants, that met inclusion-exclusion
      criteria and prespecified quality ratings. No studies were found in which primary
      care practitioners delivered counseling that followed the CMS guidelines. Mean 6
      month weight changes from baseline in the intervention groups ranged from a loss
      of 0.3 kg to 6.6 kg. In the control group, mean change ranged from a gain of 0.9
      kg to a loss of 2.0 kg. Weight loss in both groups generally declined with longer
      follow-up (12-24 months). Interventions that prescribed both reduced energy
      intake (eg, >= 500 kcal/d) and increased physical activity (eg, >=150 minutes a
      week of walking), with traditional behavioral therapy, generally produced larger
      weight loss than interventions without all 3 specific components. In the former
      trials, more treatment sessions, delivered in person or by telephone by trained
      interventionists, were associated with greater mean weight loss and likelihood of
      patients losing 5% or more of baseline weight. CONCLUSIONS AND RELEVANCE:
      Intensive behavioral counseling can induce clinically meaningful weight loss, but
      there is little research on primary care practitioners providing such care. The
      present findings suggest that a range of trained interventionists, who deliver
      counseling in person or by telephone, could be considered for treating overweight
      or obesity in patients encountered in primary care settings.

PMID- 25369492
TI  - Probiotics revisited.

PMID- 25369491
TI  - Recurrent gingival and oral mucosal lesions.

PMID- 25369493
TI  - Wearable technology with head-mounted displays and visual function.

PMID- 25369494
TI  - Anesthesia technique and outcomes after hip fracture surgery.

PMID- 25369495
TI  - Anesthesia technique and outcomes after hip fracture surgery.

PMID- 25369496
TI  - Anesthesia technique and outcomes after hip fracture surgery--reply.

PMID- 25369497
TI  - Cardiac assessment before stem cell transplantation for systemic sclerosis.

PMID- 25369498
TI  - Cardiac assessment before stem cell transplantation for systemic sclerosis-
      reply.

PMID- 25369499
TI  - Ethical considerations surrounding lethal injection.

PMID- 25369500
TI  - Ethical considerations surrounding lethal injection--reply.

PMID- 25369505
TI  - Popular beliefs and scientific facts.

PMID- 25369506
TI  - JAMA patient page. Clostridium difficile infection.

PMID- 25369507
TI  - Secular trends in menarcheal age in India-evidence from the Indian human
      development survey.
AB  - BACKGROUND: Evidence from a number of countries in Europe and North America point
      towards the secular declining trend in menarcheal age with considerable spatial
      variations over the past two centuries. Similar trends were reported in several
      developing countries from Asia, Africa and Latin America. However, data
      corroborating any secular trend in the menarcheal age of the Indian population
      remained sparse and inadequately verified. METHODS: We examined secular trends,
      regional heterogeneity and association of socioeconomic, anthropometric and
      contextual factors with menarcheal age among ever-married women (15-49 years) in
      India. Using the pseudo cohort data approach, we fit multiple linear regression
      models to estimate secular trends in menarcheal age of 91394 ever-married women
      using the Indian Human Development Survey. RESULTS: The mean age at menarche
      among Indian women was 13.76 years (95 % CI: 13.75, 13.77) in 2005. It declined
      by three months from 13.83 years (95% CI: 13.81, 13.85) among women born prior to
      1955-1964, to nearly 13.62 years (95% CI: 13.58, 13.67) among women born during
      late 1985-1989. However, these aggregate national figures mask extensive spatial
      heterogeneity as mean age at menarche varied from 15.0 years in Himachal Pradesh
      during 1955-1964 (95% CI: 14.89-15.11) to about 12.1 years in Assam (95% CI:
      11.63-12.56) during 1985-1989. CONCLUSION: The regression analysis established a
      reduction of nearly one month per decade, suggesting a secular decline in age at
      menarche among Indian women. Notably, the menarcheal age was significantly
      associated with the area of residence, geographic region, linguistic groups,
      educational attainment, wealth status, caste and religious affiliations among
      Indian women.

PMID- 25369508
TI  - Influence of the CYP2D6 isoenzyme in patients treated with venlafaxine for major
      depressive disorder: clinical and economic consequences.
AB  - BACKGROUND: Antidepressant drugs are the mainstay of drug therapy for sustained
      remission of symptoms. However, the clinical results are not encouraging. This
      lack of response could be due, among other causes, to factors that alter the
      metabolism of the antidepressant drug. OBJECTIVE: to evaluate the impact of
      concomitant administration of CYP2D6 inhibitors or substrates on the efficacy,
      tolerability and costs of patients treated with venlafaxine for major depressive
      disorder in clinical practice. METHODS: We designed an observational study using
      the medical records of outpatients. Subjects aged >= 18 years who started taking
      venlafaxine during 2008-2010 were included. Three study groups were considered:
      no combinations (reference), venlafaxine-substrate, and venlafaxine-inhibitor.
      The follow-up period was 12 months. The main variables were: demographic data,
      comorbidity, remission (Hamilton <7), response to treatment, adverse events and
      costs. The statistical analysis included logistic regression models and ANCOVA,
      with p values <0.05 considered significant. RESULTS: A total of 1,115 subjects
      were recruited. The mean age was 61.7 years and 75.1% were female. Approximately
      33.3% (95% CI: 30.5 to 36.1) were receiving some kind of drug combination
      (venlafaxine-substrate: 23.0%, and venlafaxine-inhibitor: 10.3%). Compared with
      the venlafaxine-substrate and venlafaxine-inhibitor groups, patients not taking
      concomitant drugs had a better response to therapy (49.1% vs. 39.9% and 34.3%,
      p<0.01), greater remission of symptoms (59.9% vs. 50.2% and 43.8%, p<0.001),
      fewer adverse events (1.9% vs. 7.0% and 6.1%, p<0.05) and a lower mean adjusted
      cost (?2,881.7 vs. ?4,963.3 and ?7,389.1, p<0.001), respectively. All cost
      components showed these differences. CONCLUSIONS: The patients treated with
      venlafaxine alone showed a better response to anti-depressant treatment, greater
      remission of symptoms, a lower incidence of adverse events and lower healthcare
      costs.

PMID- 25369509
TI  - Cardiac strain associated with high-rise firefighting.
AB  - Although numerous studies have reported the physiological strain associated with
      firefighting, cardiac responses during a large-scale fire operation have not been
      reported and cardiac responses have not been compared based on crew assignment.
      The aims of this study were (1) to characterize cardiac strain during simulated
      high-rise firefighting, and (2) to compare the cardiac strain associated with
      different work assignments (fire suppression vs. search and rescue) and different
      modes of vertical ascent (stairs vs. elevator). Firefighters (N = 42) completed
      one assignment (fire suppression, search and rescue, or material support) during
      one of two trials that differed by ascent mode. Assignments were divided into
      three phases: Ascent (ascend lobby to 8th floor), Staging (remain in holding area
      on 8th floor), and Work (perform primary responsibilities). When comparing
      assignments within the same ascent mode, mean heart rate (HRmean) was higher (p =
      0.031) for fire suppression than for search and rescue during Work in the stair
      trial (170 +/- 14 vs. 155 +/- 11 beats/min). Search and rescue crews experienced
      greater cumulative cardiac strain (HRmean * duration) during Work than did fire
      suppression crews (stairs: 1978 +/- 366 vs. 1502 +/- 190 beats; elevator: 1755 +/
      514 vs. 856 +/- 232 beats; p<0.05). When comparing ascent mode, HRmean and peak
      heart rate (HRpeak) were higher (35-57 beats/min; p<=0.001) for both fire
      suppression and search and rescue during Ascent and Staging phases in the stairs
      vs. the elevator trial. During Work, HRmean was higher (p = 0.046) for search and
      rescue in the stairs vs. the elevator trial (155 +/- 11 vs. 138 +/- 19
      beats/min). HRmean and HRpeak were 47 and 34 beats/min higher (p < 0.01),
      respectively, when materials were transported to the staging area using the
      stairs compared with the elevator. Study findings suggest that high-rise
      firefighting results in considerable cardiac strain and that search and rescue
      and material support crews experienced more cardiac strain than fire suppression
      crews due primarily to differences in assignment duration. Furthermore, using
      stairs to transport firefighters and equipment to upper floors results in
      significantly greater cardiac strain than using the elevator. 

PMID- 25369510
TI  - Gloss, colour and grip: multifunctional epidermal cell shapes in bee- and bird
      pollinated flowers.
AB  - Flowers bear the function of filters supporting the attraction of pollinators as
      well as the deterrence of floral antagonists. The effect of epidermal cell shape
      on the visual display and tactile properties of flowers has been evaluated only
      recently. In this study we quantitatively measured epidermal cell shape, gloss
      and spectral reflectance of flowers pollinated by either bees or birds testing
      three hypotheses: The first two hypotheses imply that bee-pollinated flowers
      might benefit from rough surfaces on visually-active parts produced by conical
      epidermal cells, as they may enhance the colour signal of flowers as well as the
      grip on flowers for bees. In contrast, bird-pollinated flowers might benefit from
      flat surfaces produced by flat epidermal cells, by avoiding frequent visitation
      from non-pollinating bees due to a reduced colour signal, as birds do not rely on
      specific colour parameters while foraging. Moreover, flat petal surfaces in bird
      pollinated flowers may hamper grip for bees that do not touch anthers and stigmas
      while consuming nectar and thus, are considered as nectar thieves. Beside this,
      the third hypothesis implies that those flower parts which are vulnerable to
      nectar robbing of bee- as well as bird-pollinated flowers benefit from flat
      epidermal cells, hampering grip for nectar robbing bees. Our comparative data
      show in fact that conical epidermal cells are restricted to visually-active parts
      of bee-pollinated flowers, whereas robbing-sensitive parts of bee-pollinated as
      well as the entire floral surface of bird-pollinated flowers possess on average
      flat epidermal cells. However, direct correlations between epidermal cell shape
      and colour parameters have not been found. Our results together with published
      experimental studies show that epidermal cell shape as a largely neglected flower
      trait might act as an important feature in pollinator attraction and avoidance of
      antagonists, and thus may contribute to the partitioning of flower-visitors. 

PMID- 25369511
TI  - Prevention of ischemic stroke in clinical practice: a role of internists and
      general practitioners.
AB  - Stroke constitutes a substantial clinical and socio-economic burden. It is
      currently the third cause of death worldwide and results in mortality or
      disability in every third patient at the end of the first year following an acute
      cerebrovascular event. Although in-hospital mortality rates in stroke patients
      have decreased, prevention and cardiovascular risk control remain critical for
      improving the prognosis and reducing stroke burden worldwide. The definitions of
      stroke and transient ischemic attack (TIA) have been recently modified following
      the findings from neuroimaging and thrombolysis research. Both stroke and TIA are
      recurrent and preventable disorders. Both patients with stroke and those with TIA
      require prompt clinical workup, risk assessment, and appropriate management
      because the risk of recurrence, stroke, and coronary events is significant. The 5
      most common cardiovascular risk factors (high blood pressure, smoking, abdominal
      obesity, diet, and lack of physical activity) are responsible for 80% of the
      cases. Stroke prevention involves lifestyle modification and specific treatment.
      Secondary prevention of ischemic stroke involves early treatment (antiplatelets
      and carotid interventions) and long-term management including lifestyle changes,
      antihypertensive therapy, antiplatelets, antithrombotic drugs in patients with
      atrial fibrillation, and the use of statins and other lipid-lowering drugs.
      Stroke patients are at risk of depression, dementia, epilepsy, and other
      complications that also require targeted treatment.

PMID- 25369512
TI  - Strawberry gingivitis as the first manifestation of granulomatosis with
      polyangiitis.

PMID- 25369513
TI  - Accurate measurement of strain ratio in quasi-static elastography.

PMID- 25369514
TI  - Accurate measurement of strain ratio in quasi-static elastography. Authors'
      reply.

PMID- 25369515
TI  - Diversity, distribution and nature of faunal associations with deep-sea
      pennatulacean corals in the Northwest Atlantic.
AB  - Anthoptilum grandiflorum and Halipteris finmarchica are two deep-sea corals
      (Octocorallia: Pennatulacea) common on soft bottoms in the North Atlantic where
      they are believed to act as biogenic habitat. The former also has a worldwide
      distribution. To assist conservation efforts, this study examines spatial and
      temporal patterns in the abundance, diversity, and nature of their faunal
      associates. A total of 14 species were found on A. grandiflorum and 6 species on
      H. finmarchica during a multi-year and multi-site sampling campaign in eastern
      Canada. Among those, 7 and 5 species, respectively, were attached to the sea pens
      and categorized as close associates or symbionts. Rarefaction analyses suggest
      that the most common associates of both sea pens have been sampled. Biodiversity
      associated with each sea pen is analyzed according to season, depth and region
      using either close associates or the broader collection of species. Associated
      biodiversity generally increases from northern to southern locations and does not
      vary with depth (~ 100-1400 m). Seasonal patterns in A. grandiflorum show higher
      biodiversity during spring/summer due to the transient presence of early life
      stages of fishes and shrimps whereas it peaks in fall for H. finmarchica. Two
      distinct endoparasitic species of highly modified copepods (families Lamippidae
      and Corallovexiidae) commonly occur in the polyps of A. grandiflorum and H.
      finmarchica, and a commensal sea anemone frequently associates with H.
      finmarchica. Stable isotope analyses (delta(13)C and delta(15)N) reveal potential
      trophic interactions between the parasites and their hosts. Overall, the
      diversity of obligate/permanent associates of sea pens is moderate; however the
      presence of mobile/transient associates highlights an ecological role that has
      yet to be fully elucidated and supports their key contribution to the enhancement
      of biodiversity in the Northwest Atlantic.

PMID- 25369517
TI  - Characterization of brain cell nuclei with decondensed chromatin.
AB  - Although multipotent cell types have enlarged nuclei with decondensed chromatin,
      this property has not been exploited to enhance the characterization of neural
      progenitor cell (NPC) populations in the brain. We found that mouse brain cell
      nuclei that expressed exceptionally high levels of the pan neuronal marker
      NeuN/FOX3 (NeuN-High) had decondensed chromatin relative to most NeuN-Low or NeuN
      Neg (negative) nuclei. Purified NeuN-High nuclei expressed significantly higher
      levels of transcripts encoding markers of neurogenesis, neuroplasticity, and
      learning and memory (ARC, BDNF, ERG1, HOMER1, NFL/NEF1, SYT1), subunits of
      chromatin modifying machinery (SIRT1, HDAC1, HDAC2, HDAC11, KAT2B, KAT3A, KAT3B,
      KAT5, DMNT1, DNMT3A, Gadd45a, Gadd45b) and markers of NPC and cell cycle activity
      (BRN2, FOXG1, KLF4, c-MYC, OCT4, PCNA, SHH, SOX2) relative to neuronal NeuN-Low
      or to mostly non-neuronal NeuN-Neg nuclei. NeuN-High nuclei expressed higher
      levels of HDAC1, 2, 4, and 5 proteins. The cortex, hippocampus, hypothalamus,
      thalamus, and nucleus accumbens contained high percentages of large decondensed
      NeuN-High nuclei, while the cerebellum, and pons contained very few. NeuN-High
      nuclei have the properties consistent with their being derived from extremely
      active neurons with elevated rates of chromatin modification and/or NPC-like
      cells with multilineage developmental potential. The further analysis of
      decondensed neural cell nuclei should provide novel insights into neurobiology
      and neurodegenerative disease.

PMID- 25369518
TI  - Heterogeneous chemistry of glyoxal on acidic solutions. An oligomerization
      pathway for secondary organic aerosol formation.
AB  - The heterogeneous chemistry of glyoxal on sulfuric acid surfaces has been
      investigated at various acid concentrations and temperatures, utilizing a low
      pressure fast flow laminar reactor coupled to an ion drift-chemical ionization
      mass spectrometer (ID-CIMS). The uptake coefficient (gamma) of glyoxal ranges
      from (1.2 +/- 0.06) * 10(-2) to (2.5 +/- 0.01) * 10(-3) for 60-93 wt % H2SO4 at
      253-273 K. The effective Henry's Law constant (H*) ranges from (98.9 +/- 4.9) *
      10(5) to (1.6 +/- 0.1) * 10(5) M atm(-1) for 60-93 wt % at 263-273 K. Both the
      uptake coefficient and Henry's Law constant increase with decreasing acid
      concentration and temperature. Our results reveal a reaction mechanism of
      hydration followed by oligomerization for glyoxal on acidic media, indicating an
      efficient aqueous reaction of glyoxal on hygroscopic particles leading to
      secondary organic aerosol formation. 

PMID- 25369519
TI  - Titanium dioxide-coated carbon nanotube network filter for rapid and effective
      arsenic sorption.
AB  - In this study, a TiO2-coated carbon nanotube (CNT) network filter was prepared
      via a simple filtration-steam hydrolysis method and evaluated with respect to
      aqueous arsenic removal. The TiO2 coating was 5.5 +/- 2.7 nm thick, completely
      covered the CNT network surface, and had a specific surface area of 196 m(2) g(
      1), which was ~2-fold greater than that of the CNT network. The TiO2-CNT As
      sorption kinetics increased with both increasing flow rate and cell potential,
      with increasing flow rate having a significantly stronger effect. At 6 mL min(-1)
      in the absence of potential and in recirculation mode, the first-order As
      sorption rate constants were 4.3 and 4.4 s(-1) for As(III) and As(V),
      respectively. The TiO2-CNT electro-assisted equilibrium sorption capacities at a
      cell potential of 2 V for effluent [As] = 10 ppb in single-pass mode were 1.8 and
      1.3 mg g(-1) for As(III) and As(V), respectively. The enhanced TiO2-CNT filter As
      sorption kinetics and capacity result from increased mass transport due to
      internal convection and pore radius range, improved sorption site accessibility
      due to porosity and TiO2 dispersion, and reduced TiO2 negative surface charge due
      to anodic capacitance. Groundwater samples containing 44 ppb As were treated by
      single-pass filtration, and 12,500 bed volumes (residence time of 4.5 s; 127 L m(
      2) h(-1); 5.8 mg m(-2) h(-1)) were filtered prior to the effluent As level
      reaching >10 ppb. A spent TiO2 filter was successfully regenerated by 5 mM NaOH
      for both As(III) and As(V).

PMID- 25369520
TI  - Modeling body mass variation: incorporating social influence into calculations of
      caloric intake and energy expenditure.
AB  - Variations in individual body mass and composition have long been a key focus in
      the health sciences, particularly now that overweight and obesity are considered
      as public health problems. We study a mathematical model that describes body mass
      variations which are determined by the energy balance between caloric intake and
      total energy expenditure. To calculate the change in caloric intake and energy
      expenditure over time, we proposed a relationship for each of these quantities,
      and we used measured values that are reported in the literature for the initial
      conditions. To account for small variations in the daily energy balance of an
      individual, we include social interactions as the multiplication of two terms:
      social proximity and social influence. We observe that social interactions have a
      considerable effect when the body mass of an individual is quite constant and
      social interactions take random values. However, when an individual's mass value
      changes (either increases or decreases), social interactions do not have a
      notable effect. In our simulation, we tested two different models that describe
      the body mass composition, and it resulted that one fits better the data. 

PMID- 25369521
TI  - Green synthesis of asymmetrically textured silver meso-flowers (AgMFs) as highly
      sensitive SERS substrates.
AB  - Highly asymmetrical "flower-like" micron silver particles, so-called hierarchical
      silver meso-flowers (AgMFs), were facilely synthesized using ascorbic acid at
      room temperature in the presence of chitosan biopolymer. The time-evolution of
      TEM images and XRD analysis confirmed the anisotropic growth of AgMFs with single
      crystalline phase of which the formation mechanism was described in detail. The
      morphology and size of as-prepared AgMFs were tunable simply by changing the
      concentration of chitosan biopolymer and/or AgNO3 precursor under otherwise
      identical conditions. The asymmetrically textured AgMFs dramatically enhanced
      Raman signals of probe molecules (2-chlorothiophenol, 4-aminothiophenol) even at
      a single particle level because of their surface morphologies consisting of
      numerous nanoedges and crevices. 

PMID- 25369522
TI  - Men's and Women's Interpretation and Endorsement of Items Measuring Self-Reported
      Heterosexual Aggression.
AB  - Early research on sexual aggression (e.g., sexual coercion, sexual assault, and
      rape) mainly focused on men as perpetrators and women as victims; more recently,
      researchers have begun to investigate women as perpetrators of sexual aggression
      as well. However, most measures of sexual aggression perpetration were designed
      for use with men and have not been well validated with women. This study sought
      to examine two different measures of sexual aggression perpetration in terms of
      their convergent validity for both men and women and to examine gender
      differences and similarities in item interpretation using open-ended inquiries.
      Participants were 590 individuals (395 women, 195 men) with a mean age of 25
      years (SD = 8.1) recruited from an undergraduate psychology subject pool and an
      online convenience sample. The majority of the sample was White (65.4%) and Black
      (20.3%). All measures were completed online anonymously. Results suggested that
      convergent validity for the two measures was less than optimal, particularly for
      women. Further, item interpretation analyses revealed that, compared to men, more
      than twice the percentage of women provided a false-positive response to one of
      the measures, suggesting that women may be more likely than men to endorse self
      report perpetration items incorrectly.

PMID- 25369524
TI  - Two-Photon Excitation of trans-Stilbene: Spectroscopy and Dynamics of
      Electronically Excited States above S1.
AB  - The photoisomerization dynamics of trans-stilbene have been well studied in the
      lowest excited state, but much less is known about the behavior following
      excitation to higher-lying electronically excited states. This contribution
      reports a combined study of the spectroscopy and dynamics of two-photon
      accessible states above S1. Two-photon absorption (2PA) measurements using a
      broadband pump-probe technique reveal distinct bands near 5.1 and 6.4 eV. The 2PA
      bands have absolute cross sections of 40 +/- 16 and 270 +/- 110 GM, respectively,
      and a pump-probe polarization dependence that suggests both of the transitions
      access Ag-symmetry excited states. Separate transient absorption measurements
      probe the excited-state dynamics following two-photon excitation into each of the
      bands using intense pulses of 475 and 380 nm light, respectively. The initially
      excited states rapidly relax via internal conversion, leading to the formation of
      an S1 excited-state absorption band that is centered near 585 nm and evolves on a
      time scale of 1-2 ps due to intramolecular vibrational relaxation. The subsequent
      evolution of the S1 excited-state absorption is identical to the behavior
      following direct one-photon excitation of the lowest excited state at 4.0 eV. The
      complementary spectroscopy and dynamics measurements provide new benchmarks for
      computational studies of the electronic structure and dynamics of this model
      system on excited states above S1. Probing the dynamics of molecules in their
      higher-lying excited states is an important frontier in chemical reaction
      dynamics. 

PMID- 25369523
TI  - Asymmetrical effect of levodopa on the neural activity of motor regions in PD.
AB  - Parkinson's disease (PD) is a neurodegenerative illness often characterized by
      asymmetrical symptoms. However, the reason for this asymmetry and the cerebral
      correlates underlying symptom asymmetry are still not well understood.
      Furthermore, the effects of levodopa on the cerebral correlates of disease
      asymmetry have not been investigated. In this study, right-handed PD patients
      performed self-initiated, externally triggered and repetitive control finger
      movements with both their right and left hands during functional magnetic
      resonance imaging (fMRI) to investigate asymmetrical effects of levodopa on the
      hemodynamic correlates of finger movements. Patients completed two experimental
      sessions OFF and ON medication after a minimum of 12 hours medication withdrawal.
      We compared the effect of levodopa on the neural activation patterns underlying
      the execution of both the more affected and less affected hand for self-initiated
      and externally triggered movements. Our results show that levodopa led to larger
      differences in cerebral activity for movements of the more affected, left side:
      there were significant differences in activity after levodopa administration in
      regions of the motor cortico-striatal network when patients performed self
      initiated and externally triggered movements with their left hand. By contrast,
      when patients used their right hand, levodopa led to differences in cerebellar
      activity only. As our patients were affected more severely on their left side, we
      propose that levodopa may help provide additional dopaminergic input, improving
      movements for the more severely affected side. These results suggest that the
      impact of reduced dopamine in the cortico-striatal system and the action of
      levodopa is not symmetrical. 

PMID- 25369525
TI  - The effect of a cadence retraining protocol on running biomechanics and
      efficiency: a pilot study.
AB  - Many studies have documented the association between mechanical deviations from
      normal and the presence or risk of injury. Some runners attempt to change
      mechanics by increasing running cadence. Previous work documented that increasing
      running cadence reduces deviations in mechanics tied to injury. The long-term
      effect of a cadence retraining intervention on running mechanics and energy
      expenditure is unknown. This study aimed to determine if increasing running
      cadence by 10% decreases running efficiency and changes kinematics and kinetics
      to make them less similar to those associated with injury. Additionally, this
      study aimed to determine if, after 6 weeks of cadence retraining, there would be
      carryover in kinematic and kinetic changes from an increased cadence state to a
      runner's preferred running cadence without decreased running efficiency. We
      measured oxygen uptake, kinematic and kinetic data on six uninjured participants
      before and after a 6-week intervention. Increasing cadence did not result in
      decreased running efficiency but did result in decreases in stride length, hip
      adduction angle and hip abductor moment. Carryover was observed in runners' post
      intervention preferred running form as decreased hip adduction angle and vertical
      loading rate.

PMID- 25369527
TI  - A hybrid non-ribosomal peptide/polyketide synthetase containing fatty-acyl ligase
      (FAAL) synthesizes the beta-amino fatty acid lipopeptides puwainaphycins in the
      Cyanobacterium Cylindrospermum alatosporum.
AB  - A putative operon encoding the biosynthetic pathway for the cytotoxic
      cyanobacterial lipopeptides puwainphycins was identified in Cylindrospermum
      alatosporum. Bioinformatics analysis enabled sequential prediction of
      puwainaphycin biosynthesis; this process is initiated by the activation of a
      fatty acid residue via fatty acyl-AMP ligase and continued by a multidomain non
      ribosomal peptide synthetase/polyketide synthetase. High-resolution mass
      spectrometry and nuclear magnetic resonance spectroscopy measurements proved the
      production of puwainaphycin F/G congeners differing in FA chain length formed by
      either 3-amino-2-hydroxy-4-methyl dodecanoic acid (4-methyl-Ahdoa) or 3-amino-2
      hydroxy-4-methyl tetradecanoic acid (4-methyl-Ahtea). Because only one
      puwainaphycin operon was recovered in the genome, we suggest that the fatty acyl
      AMP ligase and one of the amino acid adenylation domains (Asn/Gln) show extended
      substrate specificity. Our results provide the first insight into the
      biosynthesis of frequently occurring beta-amino fatty acid lipopeptides in
      cyanobacteria, which may facilitate analytical assessment and development of
      monitoring tools for cytotoxic cyanobacterial lipopeptides. 

PMID- 25369528
TI  - Quantitative assessment of murine articular cartilage and bone using X-ray phase
      contrast imaging.
AB  - Murine models for rheumatoid arthritis (RA) research can provide important
      insights for understanding RA pathogenesis and evaluating the efficacy of novel
      treatments. However, simultaneously imaging both murine articular cartilage and
      subchondral bone using conventional techniques is challenging because of low
      spatial resolution and poor soft tissue contrast. X-ray phase-contrast imaging
      (XPCI) is a new technique that offers high spatial resolution for the
      visualisation of cartilage and skeletal tissues. The purpose of this study was to
      utilise XPCI to observe articular cartilage and subchondral bone in a collagen
      induced arthritis (CIA) murine model and quantitatively assess changes in the
      joint microstructure. XPCI was performed on the two treatment groups (the control
      group and CIA group, n = 9 per group) to monitor the progression of damage to the
      femur from the knee joint in a longitudinal study (at 0, 4 and 8 weeks after
      primary injection). For quantitative assessment, morphologic parameters were
      measured in three-dimensional (3D) images using appropriate image analysis
      software. Our results showed that the average femoral cartilage volume, surface
      area and thickness were significantly decreased (P<0.05) in the CIA group
      compared to the control group. Meanwhile, these decreases were accompanied by
      obvious destruction of the surface of subchondral bone and a loss of trabecular
      bone in the CIA group. This study confirms that XPCI technology has the ability
      to qualitatively and quantitatively evaluate microstructural changes in mouse
      joints. This technique has the potential to become a routine analysis method for
      accurately monitoring joint damage and comprehensively assessing treatment
      efficacy.

PMID- 25369530
TI  - Cardiac MR assessment of cardiac myxomas.
AB  - Cardiac myxomas are the most common benign primary cardiac tumour to present in
      adulthood. While most patients present with symptoms of cardiac obstruction,
      embolic phenomena or constitutional impairment, up to a fifth of patients remain
      asymptomatic and are incidentally diagnosed on imaging. Although echocardiography
      is usually the initial imaging modality used to evaluate these patients, cardiac
      MRI (CMR) has emerged over the past decade as the primary imaging modality in the
      assessment of patients with cardiac tumours. The superior tissue characterization
      capability of CMR means that it is able to determine the nature of some tumours
      pre-operatively and performs well in differentiating myxomas from thrombus. We
      present a pictorial review highlighting the key CMR features of myxomas and show
      how these lesions can be differentiated from thrombus and other cardiac masses. 

PMID- 25369529
TI  - YAP/TEAD co-activator regulated pluripotency and chemoresistance in ovarian
      cancer initiated cells.
AB  - Recent evidence suggests that some solid tumors, including ovarian cancer,
      contain distinct populations of stem cells that are responsible for tumor
      initiation, growth, chemo-resistance, and recurrence. The Hippo pathway has
      attracted considerable attention and some investigators have focused on YAP
      functions for maintaining stemness and cell differentiation. In this study, we
      successfully isolated the ovarian cancer initiating cells (OCICs) and
      demonstrated YAP promoted self-renewal of ovarian cancer initiated cell (OCIC)
      through its downstream co-activator TEAD. YAP and TEAD families were required for
      maintaining the expression of specific genes that may be involved in OCICs'
      stemness and chemoresistance. Taken together, our data first indicate that
      YAP/TEAD co-activator regulated ovarian cancer initiated cell pluripotency and
      chemo-resistance. It proposed a new mechanism on the drug resistance in cancer
      stem cell that Hippo-YAP signal pathway might serve as therapeutic targets for
      ovarian cancer treatment in clinical. 

PMID- 25369531
TI  - Is the person-situation debate important for agent-based modeling and vice-versa?
AB  - BACKGROUND: Agent-based models (ABM) are believed to be a very powerful tool in
      the social sciences, sometimes even treated as a substitute for social
      experiments. When building an ABM we have to define the agents and the rules
      governing the artificial society. Given the complexity and our limited
      understanding of the human nature, we face the problem of assuming that either
      personal traits, the situation or both have impact on the social behavior of
      agents. However, as the long-standing person-situation debate in psychology
      shows, there is no consensus as to the underlying psychological mechanism and the
      important question that arises is whether the modeling assumptions we make will
      have a substantial influence on the simulated behavior of the system as a whole
      or not. METHODOLOGY/PRINCIPAL FINDINGS: Studying two variants of the same agent
      based model of opinion formation, we show that the decision to choose either
      personal traits or the situation as the primary factor driving social
      interactions is of critical importance. Using Monte Carlo simulations (for
      Barabasi-Albert networks) and analytic calculations (for a complete graph) we
      provide evidence that assuming a person-specific response to social influence at
      the microscopic level generally leads to a completely different and less
      realistic aggregate or macroscopic behavior than an assumption of a situation
      specific response; a result that has been reported by social psychologists for a
      range of experimental setups, but has been downplayed or ignored in the opinion
      dynamics literature. SIGNIFICANCE: This sensitivity to modeling assumptions has
      far reaching consequences also beyond opinion dynamics, since agent-based models
      are becoming a popular tool among economists and policy makers and are often used
      as substitutes of real social experiments.

PMID- 25369532
TI  - Carboxyl-ester lipase maturity-onset diabetes of the young disease protein
      biomarkers in secretin-stimulated duodenal juice.
AB  - Patients with carboxyl-ester lipase-maturity-onset diabetes of the young (CEL
      MODY) display distinct disease stages toward the development of monogenic
      diabetes and exocrine pancreatic disease. The finding of differentially increased
      proteins, some related to MAPK signaling, in a discovery proteomics study of
      secretin-stimulated duodenal juice in three CEL-MODY patients, prompted us to
      monitor their abundance in an extensive number of CEL-MODY subjects at different
      disease stages and controls using targeted proteomics. In the current study, we
      demonstrate the feasibility of selected reaction monitoring assays to quantify
      protein levels in secretin-stimulated duodenal juice. Furthermore, we define a
      set of five peptides for potential use as diagnostic tests in CEL-MODY patients.
      Finally, we propose a further set of seven proteins with a likely pathogenic role
      in CEL-MODY disease progression. 

PMID- 25369533
TI  - Multiplexed analysis of genes and of metal ions using enzyme/DNAzyme
      amplification machineries.
AB  - The progressive development of amplified DNA sensors using nucleic acid-based
      machineries, involving the isothermal autonomous synthesis of the Mg(2+)
      dependent DNAzyme, is used for the amplified, multiplexed analysis of genes
      (Smallpox, TP53) and metal ions (Ag(+), Hg(2+)). The DNA sensing machineries are
      based on the assembly of two sensing modules consisting of two nucleic acid
      scaffolds that include recognition sites for the two genes and replication tracks
      that yield the nicking domains for Nt.BbvCI and two different Mg(2+)-dependent
      DNAzyme sequences. In the presence of any of the genes or the genes together,
      their binding to the respective recognition sequences triggers the
      nicking/polymerization machineries, leading to the synthesis of two different
      Mg(2+)-dependent DNAzyme sequences. The cleavage of two different
      fluorophore/quencher-modified substrates by the respective DNAzymes leads to the
      fluorescence of F1 and/or F2 as readout signals for the detection of the genes.
      The detection limits for analyzing the Smallpox and TP53 genes correspond to 0.1
      nM. Similarly, two different nucleic acid scaffolds that include Ag(+)-ions or
      Hg(2+)-ions recognition sequences and the replication tracks that yield the
      Nt.BbvCI nicking domains and the respective Mg(2+)-dependent DNAzyme sequences
      are implemented as nicking/replication machineries for the amplified, multiplexed
      analysis of the two ions, with detection limits corresponding to 1 nM. The ions
      sensing modules reveal selectivities dominated by the respective recognition
      sequences associated with the scaffolds.

PMID- 25369534
TI  - Construction of dispirocyclohexanes via amine-catalyzed [2 + 2 + 2] annulations
      of Morita-Baylis-Hillman acetates with exocyclic alkenes.
AB  - Amine-catalyzed [2 + 2 + 2] annulations of one molecule of Morita-Baylis-Hillman
      (MBH) acetates 1 with two molecules of 2-(arylmethylidene)indane-1,3-diones 2 or
      methyleneindolinones 4 have been developed under very mild conditions, which
      produce multistereogenic dispirocyclohexanes 3 and 5, respectively, in moderate
      to excellent yields and good diastereoselectivity. This amine-catalyzed
      annulation constitutes a novel and efficient method for the construction of
      dispirocyclohexane motifs, and also showcases the divergent catalysis between
      amines and phosphines with regard to the corresponding phosphine-catalyzed [3 +
      2] annulations. 

PMID- 25369535
TI  - Microlaparoscopy versus conventional laparoscopy in transperitoneal pyeloplasty.
AB  - BACKGROUND AND PURPOSE: Laparoscopic pyeloplasty has emerged as the gold standard
      for repair of ureteropelvic junction obstruction. Microlaparoscopic (MLP, <3 mm)
      instrumentation has improved markedly and can now be used for suturing and
      complex dissection needed during laparoscopic pyeloplasty. We present our
      experience with microlaparoscopy compared with conventional laparoscopy for
      transperitoneal pyeloplasty. METHODS: We performed a retrospective analysis of
      hybrid MLP, using a 5-mm camera in a hidden umbilical incision, and 1.9 or 3 mm
      working instruments and compared with patients undergoing conventional
      laparoscopic pyeloplasty (CLP). The data for MLP and CLP were compared using the
      Student t test, Pearson chi-square test, and Fisher exact test, where
      appropriate. RESULTS: Between January 2009 and May 2013, there were 19 MLP and 27
      CLP procedures performed. The MLP group mean age was younger than the CLP group
      (34 vs 50 years; P=0.0003). Body mass index, previous treatment rates, operative
      time, length of stay, ureteral stent duration, and complication rates were not
      statistically different between the MLP and CLP groups. Strict success rates
      (indicated by follow-up renal scan T1/2<20 min) were similar between MLP and CLP
      groups (89.5% vs 88.9%; P=0.95). No MLP procedures were converted to CLP or open
      approaches. CONCLUSIONS: From technical, perioperative, and outcome perspectives,
      transperitoneal pyeloplasty with microlaparoscopy is both safe and feasible in
      our hands compared with conventional laparoscopy, and results in subjectively
      superior cosmesis. This is the largest MLP series to date and contains, to our
      knowledge, the only cases described using prototype 1.9 mm instruments.

PMID- 25369538
TI  - Thermochemical insights on the conformational energetics of azepan and azepan-1
      ylacetonitrile.
AB  - This paper is concerned with computational and experimental thermochemical
      studies of azepan and azepan-1-ylacetonitrile, molecules whose flexible ring
      structure provides several conformational forms with low energy barriers among
      them. The computational study describes the energetic analysis of the six most
      stable conformers on the potential energy surfaces and the determination of their
      gas-phase standard enthalpy of formation at the reference temperature of 298.15
      K. The same gas-phase enthalpic parameters are also derived from the enthalpies
      of formation in the liquid phase and the enthalpies of vaporization, at T =
      298.15 K, determined experimentally using the combustion calorimetry and the
      Calvet microcalorimetry techniques, respectively. The experimental data reported
      in this work for the two titled compounds together with other available in the
      literature for related molecules enabled the establishment of an increments
      scheme, providing a reliable approach on the prevision of gas-phase enthalpy of
      formation of cyclic/acyclic hydrocarbons and amines. Complementary, natural bond
      orbital (NBO) calculations were also performed, allowing an advance on the
      analysis of the structural and reactivity behavior of these type of compounds. 

PMID- 25369536
TI  - The non-small cell lung cancer immune contexture. A major determinant of tumor
      characteristics and patient outcome.
AB  - Solid tumors, beyond mere accumulation of cancer cells, form a complex ecosystem
      consisting of normal epithelial cells, fibroblasts, blood and lymphatic vessels,
      structural components, and infiltrating hematopoietic cells including myeloid and
      lymphoid elements that impact tumor growth, tumor spreading, and clinical
      outcome. The composition of the immune microenvironment is diverse, including
      various populations of T cells, B cells, dendritic cells, natural killer cells,
      myeloid-derived suppressor cells, neutrophils, or macrophages. The immune
      contexture describes the density, location, and organization of these immune
      cells within solid tumors. In lung cancer, which is the deadliest type of cancer,
      and particularly in non-small cell lung cancer, its most prevalent form, reports
      have described some of the interactions between the tumor and the host. These
      data, in addition to articles on various types of tumors, provide a greater
      understanding of the tumor-host microenvironment interaction and stimulate the
      development of prognostic and predictive biomarkers, the identification of novel
      target antigens for therapeutic intervention, and the implementation of tools for
      long-term management of patients with cancer.

PMID- 25369540
TI  - Visible-light-driven difluoroacetamidation of unactive arenes and heteroarenes by
      direct C-H functionalization at room temperature.
AB  - The directed difluoroacetamidation of unactivated arenes and heteroarenes with
      bromodifluoroacetamides via visible-light photoredox catalysis has been
      efficiently achieved at room temperature. Broad utility of this transformation is
      presented, including electronically deficient heteroaromatic and aromatic
      systems. The mechanistic pathway of the difluoroacetamidation was discussed based
      on photoluminescence quenching, spin-trapping, and kinetic isotope effect
      experiments.

PMID- 25369541
TI  - Release of nanoclay and surfactant from polymer-clay nanocomposites into a food
      simulant.
AB  - Release assessment of organo-modified montmorillonite (O-MMT) nanoclay and the
      organo-modifiers (surfactants) was performed on two types of polymer-clay
      nanocomposites: polypropylene (PP) and polyamide 6 (PA6) with O-MMT. In
      accordance with ASTM D4754-11, nanocomposite films were exposed to ethanol as a
      fatty-food simulant at 70  degrees C. The release of O-MMT, with Si and Al used
      as the nanoclay markers, was evaluated by graphite furnace atomic absorption
      spectrometry. The nanoclay particles released in ethanol were visualized by
      transmission electron microscopy (TEM). More nanoclay particles were released
      from PP-clay films (0.15 mg L(-1)) than from PA6-clay films (0.10 mg L(-1)),
      possibly due to the lack of interaction between the nanoclay and PP as indicated
      by the structure and morphology in the TEM images. The surfactant release was
      quantified by a liquid chromatography tandem mass spectrometry (LC-MS/MS) method.
      A substantial amount of surfactant was released into ethanol (3.5 mg L(-1) from
      PP-clay films and 16.2 mg L(-1) from PA6-clay films), indicating changes in the
      nanoclay structure within the nanocomposite while it was exposed to ethanol. This
      research has provided information for the determination of exposure doses of
      nanoclay and surfactant in biosystems and the environment, which enabled the risk
      assessment.

PMID- 25369539
TI  - SAR156497, an exquisitely selective inhibitor of aurora kinases.
AB  - The Aurora family of serine/threonine kinases is essential for mitosis. Their
      crucial role in cell cycle regulation and aberrant expression in a broad range of
      malignancies have been demonstrated and have prompted intensive search for small
      molecule Aurora inhibitors. Indeed, over 10 of them have reached the clinic as
      potential anticancer therapies. We report herein the discovery and optimization
      of a novel series of tricyclic molecules that has led to SAR156497, an
      exquisitely selective Aurora A, B, and C inhibitor with in vitro and in vivo
      efficacy. We also provide insights into its mode of binding to its target
      proteins, which could explain its selectivity. 

PMID- 25369537
TI  - Hyperpolarized magnetic resonance as a sensitive detector of metabolic function.
AB  - Hyperpolarized magnetic resonance allows for noninvasive measurements of
      biochemical reactions in vivo. Although this technique provides a unique tool for
      assaying enzymatic activities in intact organs, the scope of its application is
      still elusive for the wider scientific community. The purpose of this review is
      to provide key principles and parameters to guide the researcher interested in
      adopting this technology to address a biochemical, biomedical, or medical issue.
      It is presented in the form of a compendium containing the underlying essential
      physical concepts as well as suggestions to help assess the potential of the
      technique within the framework of specific research environments. Explicit
      examples are used to illustrate the power as well as the limitations of
      hyperpolarized magnetic resonance. 

PMID- 25369542
TI  - Fine-needle aspiration biopsy of secondary neoplasms of the thyroid gland: a
      multi-institutional study of 62 cases.
AB  - BACKGROUND: Secondary neoplasms of the thyroid gland (SNTGs) are uncommon, and it
      is important to recognize them in thyroid fine-needle aspiration biopsy (FNAB).
      METHODS: The authors report a cohort of 62 SNTGs from 7 institutions in the
      United States and Europe. Patients were identified retrospectively by searching
      through medical records of the respective institutions. All initial diagnoses
      were rendered by FNAB. RESULTS: SNTGs represented 0.16% of all thyroid FNABs and
      were more frequent among women (ratio of women to men, 1.2:1.0). The mean patient
      age was of 59 years (range, 7-84 years), the mean tumor size was 3 cm (range, 0.9
      7 cm), and the mean interval from diagnosis of the primary tumor was 45 months
      (range, 0-156 months). Eighty-seven percent of SNTGs were diagnosed as malignant
      by FNAB, and there was a specific SNTG diagnosis in 93% of patients.
      Immunocytochemistry and flow cytometry, which were used in 30% of patients, were
      useful ancillary studies. Adenocarcinomas (n = 23; 37%) and squamous cell
      carcinomas (SCCs) (n = 22; 35.5%) represented the majority of SNTGs, followed by
      lymphoma (n = 5; 8%), melanoma (n = 5; 8%), adenoid cystic carcinoma (n = 3; 5%),
      and various sarcomas (n = 3; 5%). Adenocarcinomas originated from the kidney (n =
      9; 39%), lung (n = 6; 26%), breast (n = 5; 22%), and colon (n = 3; 13%). SCCs
      originated mostly from the head and neck (n = 13; 59%), followed by lung (n = 3;
      13%), esophagus (n = 3; 14%), and unknown primary sites (n = 3; 14%).
      CONCLUSIONS: Adenocarcinomas from the kidney, lung, breast, and colon along with
      SCCs represent the majority of SNTGs. The current results indicate that FNAB is a
      sensitive and accurate method for diagnosing SNTG; however, diagnostic
      difficulties can occur. Knowledge of clinical history and the judicious
      application of ancillary studies can increase the sensitivity and accuracy of
      FNAB for detecting SNTGs.

PMID- 25369543
TI  - Insights into Pseudomonas aeruginosa ATCC9027 resistance to isothiazolones
      through proteomics.
AB  - Although many explanations have been proposed for drug resistance to
      isothiazolones, the scope of cellular and physiological changes associated with
      this resistance remains unclear. In this study, comparative proteomic profiles of
      Pseudomonas aeruginosa ATCC9027 (WT) and an induced strain of Pa-R, which showed
      resistance to Kathon (a type of isothiazolone), were characterized using two
      dimensional electrophoresis and matrix-assisted desorption/ionization time-of
      flight mass spectroscopy. The results showed that a total of 16 proteins were
      successfully identified, among which 5 proteins were upregulated and 11 proteins
      were found to be repressed in Pa-R. At the same time, there were 14 proteins that
      contributed to metabolic processes, 1 protein (ATP-binding component of ATP
      binding cassette [ABC] transporter) was the cellular component, and 1 protein
      (LolA) exhibited a transporter activity. The respective gene expression patterns
      of all the identified proteins in both Pa-R and WT were also evaluated by
      quantitative real-time polymerase chain reaction and shown to consistently
      correlate with those deduced from the proteomic results. Moreover, the resistant
      levels of Pa-R and WT could be affected by temperature and pH. Additionally, Pa-R
      exhibited coresistance and cross-resistance to other types of antimicrobial
      agents. Our results suggest that the resistant levels of P. aeruginosa to
      isothiazolones could be affected by extracellular factors and the resistance
      features are a complex system. 

PMID- 25369548
TI  - Using the ANGELO model to develop the children's healthy living program
      multilevel intervention to promote obesity preventing behaviors for young
      children in the U.S.-affiliated Pacific Region.
AB  - BACKGROUND: Almost 40% of children are overweight or obese by age 8 years in the
      US-Affiliated Pacific, inclusive of the five jurisdictions of Alaska, Hawaii,
      American Samoa, Guam, and the Commonwealth of the Northern Mariana Islands. This
      article describes how the Children's Healthy Living (CHL) Program used the ANGELO
      (Analysis Grid for Environments/Elements Linked to Obesity) model to design a
      regional intervention to increase fruit and vegetable intake, water consumption,
      physical activity, and sleep duration and decrease recreational screen time and
      sugar-sweetened beverage consumption in young children ages 2-8 years. METHODS:
      Using the ANGELO model, CHL (1) engaged community to identify preferred
      intervention strategies, (2) reviewed scientific literature, (3) merged findings
      from community and literature, and (4) formulated the regional intervention.
      RESULTS: More than 900 community members across the Pacific helped identify
      intervention strategies on importance and feasibility. Nine common intervention
      strategies emerged. Participants supported the idea of a regional intervention
      while noting that cultural and resource differences would require flexibility in
      its implementation in the five jurisdictions. Community findings were merged with
      the effective obesity-reducing strategies identified in the literature, resulting
      in a regional intervention with four cross-cutting functions: (1) initiate or
      strengthen school wellness policies; (2) partner and advocate for environmental
      change; (3) promote CHL messages; and (4) train trainers to promote CHL
      behavioral objectives for children ages 2-8 years. These broad functions guided
      intervention activities and allowed communities to tailor activities to maximize
      intervention fit. CONCLUSIONS: Using the ANGELO model assured that the regional
      intervention was evidence based while recognizing jurisdiction context, which
      should increase effectiveness and sustainability.

PMID- 25369549
TI  - Evaluation of Occlusion Treatment Outcomes for Unilateral Amblyopia Using
      Different Definitions of Outcome.
AB  - We studied 87 cases of children aged 3 to 10 with unilateral amblyopia (with
      types of anisometropia, strabismus, or both) who received good recovery after
      occlusion therapy. The proportional improvement had moderate positive correlation
      with amblyopic eye improvement (p < 0.05) and negative correlation with residual
      amblyopia (p < 0.05); the amblyopia residual had no correlation with amblyopic
      eye improvement (p < 0.05). In multivariate analysis, the proportion of the
      deficit-corrected of the <5 years group with 2 h/d occlusion therapy group
      displayed the best outcome (p < 0.05). The BCVA of amblyopia eye and residual
      amblyopia are simple and direct indicators for clinical application. The
      proportion of the deficit-corrected method should be graded as the proportion of
      change in visual acuity with respect to the absolute potential for improvement,
      and these optimum outcomes can provide powerful evidence for good therapeutic
      effect. 

PMID- 25369550
TI  - Selectivity in ROS-induced peptide backbone bond cleavage.
AB  - Post-translational mechanisms of protein oxidation as a result of reactive oxygen
      species (ROS) can occur under physiological conditions to yield selective side
      chain and backbone modifications including abstractions, donations, additions,
      substitutions, and fragmentation. In order to characterize the selectivity of
      radical-mediated fragmentation, quantum mechanical investigations using ab initio
      and density functional methods were employed to evaluate site, conformation, and
      pathway trends of small trialanine peptides resembling a beta-strand and a beta
      turn. Comparisons of reaction enthalpies show that the diamide pathway is more
      energetically favorable than the alpha-amidation pathway and that both pathways
      are site and conformationally selective. These findings readily contribute to the
      understanding of oxidative stress in biochemical processes. 

PMID- 25369551
TI  - Altered profile of circulating microparticles in rheumatoid arthritis patients.
AB  - Microparticles (MPs) could be considered biomarkers of cell damage and activation
      as well as novel signalling structures. Since rheumatoid arthritis (RA) is
      characterized by immune and endothelial activation, the main aim of the present
      study was to analyse MP counts in RA patients. Citrated-blood samples were
      obtained from 114 RA patients, 33 healthy controls (HC) and 72 individuals with
      marked cardiovascular (CV) risk without autoimmune manifestations (CVR). MPs were
      analysed in platelet-poor plasma (PPP) and different subsets were identified by
      their surface markers: platelet- (CD41+), endothelial- (CD146+), granulocyte-
      (CD66+), monocyte- (CD14+) and Tang- (CD3+CD31+) derived. Disease activity score
      (DAS28), clinical and immunological parameters as well as traditional CV risk
      factors (diabetes, hypertension, dyslipidaemia and obesity) were registered from
      clinical records and all data were integrated using Principal Component Analysis
      (PCA). Absolute MP number was increased in RA patients compared with HC and
      positively correlated with traditional CV risk factors, similar to that of CVR
      subjects. In addition, frequency of the different MP subsets was different in RA
      patients and significantly associated with disease features. Moreover, in vitro
      assays revealed that MPs isolated from RA patients were able to promote
      endothelial activation and exhibited detrimental effects on human microvascular
      endothelial cells (HMEC-I) endothelial cell functionality. Circulating MPs from
      RA patients displayed quantitative and qualitative alterations that are the
      result of both disease-specific and traditional CV risk factors. Accordingly,
      this MP pool exhibited in vitro detrimental effects on endothelial cells, thus
      supporting their role as biomarkers of vascular damage.

PMID- 25369552
TI  - Evolution alters the enzymatic reaction coordinate of dihydrofolate reductase.
AB  - How evolution has affected enzyme function is a topic of great interest in the
      field of biophysical chemistry. Evolutionary changes from Escherichia coli
      dihydrofolate reductase (ecDHFR) to human dihydrofolate reductase (hsDHFR) have
      resulted in increased catalytic efficiency and an altered dynamic landscape in
      the human enzyme. Here, we show that a subpicosecond protein motion is
      dynamically coupled to hydride transfer catalyzed by hsDHFR but not ecDHFR. This
      motion propagates through residues that correspond to mutational events along the
      evolutionary path from ecDHFR to hsDHFR. We observe an increase in the
      variability of the transition states, reactive conformations, and times of
      barrier crossing in the human system. In the hsDHFR active site, we detect
      structural changes that have enabled the coupling of fast protein dynamics to the
      reaction coordinate. These results indicate a shift in the DHFR family to a form
      of catalysis that incorporates rapid protein dynamics and a concomitant shift to
      a more flexible path through reactive phase space. 

PMID- 25369553
TI  - Prevalence and associated factors of mental health problems among monogamous
      Chinese female patients with sexually transmitted diseases in Hong Kong.
AB  - Sexually transmitted disease (STD) increases risk of HIV infection and has
      profound psychological consequences. The present study examined the mental health
      problems (poor emotional well-being, insomnia, probable depression) and their
      associated factors among monogamous Chinese female STD patients. A total of 537
      Chinese female STD patients who self-reported having had only one male sex
      partner in the last 12 months were recruited from a STD clinic in Hong Kong. They
      completed a survey including measures of mental health, STD-related history,
      perceptions, feelings related to STD infection, and perceptions toward condom
      use. Results showed that 22% had poor emotional well-being, 25.7% had insomnia,
      and 43% were probable cases of depression. Unemployment, worsened relationship
      with partners after STD diagnosis, STD history in last three months, finding STD
      examinations embarrassing, and feelings of helplessness were significant risk
      factors for poor emotional well-being and insomnia. Also, unemployment, worsened
      relationships with partners after STD diagnosis, and perceived high chance of STD
      in the coming six months were significant risk factors for probable depression.
      Perceived efficacy of condom use for STD prevention was a significant protective
      factor against poor emotional well-being and probable depression. Findings
      suggest that interventions are warranted to improve the mental health among this
      population. 

PMID- 25369554
TI  - Male Role Endorsement Explains Negative Attitudes Toward Lesbians and Gay Men
      Among Students in Mexico More Than in Germany.
AB  - Anti-gay attitudes vary across cultures because the larger social context plays a
      role in attitude formation. Psychological correlates of these attitudes have been
      investigated in the United States and Europe. Endorsement of traditional gender
      roles has emerged from that research as a central correlate, next to religiosity
      and personal contact with lesbians/gay men. In a cross-sectional study, we tested
      whether these correlates are relevant in Mexico, characterized as an androcentric
      culture in which both gender-role traditionalism and religiosity are high, using
      a college-age student sample (N = 63). Because we relied on self-reports, the
      motivation to appear nonprejudiced was also assessed. We found typical gender
      differences in attitudes toward gay men. In bivariate tests, anti-gay attitudes
      were related to male role endorsement, contact with lesbians/gay men, and
      religiosity. In a multivariate analysis, variance in attitudes was explained by
      male role endorsement; personal contact or religiosity did not explain additional
      variance. In a German comparison sample (N = 112), male role endorsement played a
      smaller role. Variance in anti-gay attitudes in the German sample was also
      related to personal contact, religiosity, and the motivation to appear
      nonprejudiced. We discuss the centrality of (male) gender-role endorsement in
      cultures with high gender-role traditionalism.

PMID- 25369555
TI  - Formation of double-strand dimetallic helicates with a terpyridine-based
      macrocycle.
AB  - The macrocyclic ligand (L), containing two terpyridine (terpy) and two
      ethylenediamine (en) groups arranged in a cyclic terpy-en-terpy-en sequence,
      forms a double-strand helicate Cu2L(4+) complex made especially stable by the
      formation of interstrand pi-pi stacking interactions involving opposite pyridine
      rings. The crystal structure of this complex shows the Cu(2+) cations in square
      pyramidal coordination environments defined by the donor atoms of half ligand
      chain composed, in sequence, by one pyridine ring, the connected ethylenediamine
      moiety and the two adjacent pyridine rings of the successive terpyridine. In
      aqueous solution, L forms both mono- and binuclear complexes with Cu(2+). The
      stability constants determined for these complexes evidence the combined action
      of the two metal ions in the assembly of the very stable helicate species, the
      binding of the first metal ion favoring the entrance of the second one. UV
      adsorption and emission spectra corroborate these equilibrium results.
      Furthermore, the Cu2L(4+) complex shows a significant inertness toward
      dissociation in acidic solutions. Also Zn(2+) forms mono- and binuclear complexes
      with L, although the Zn2L(4+) complex is much weaker than the Cu2L(4+) helicate
      and gives rise to fast dissociation reactions in acidic media. Experimental
      evidence allows neither to say that also the Zn(2+) complex has a helicate
      structure nor to exclude it. 

PMID- 25369556
TI  - Template-independent, in situ grown DNA nanotail enabling label-free femtomolar
      chronocoulometric detection of nucleic acids.
AB  - A routine electrochemical DNA (E-DNA) sensor requires either an exquisite design
      of conformation-switchable recognition probe that is critical to facilitate
      electron transfer at a sensing interface, or a template-dependent DNA
      amplification, which often involves designing prone-to-false "sticky ends" and
      labeling redox tags at one end of the signal probes. Here we report an in situ
      grown DNA nanotail (IGT)-mediated straightforward and template-free signal
      amplification strategy for highly sensitive and sequence-specific DNA detection.
      This novel electrochemical IGT (E-IGT) DNA sensor can quantify target nucleic
      acids in a label-free manner because the electrochemical signals are generated by
      chronocoulometric interrogation of redox [Ru(NH3)6](3+) that electrostatically
      and quantitatively binds to the negatively charged phosphate moieties in the
      electrode surface-attached DNA. By introduction of terminal deoxynucleoside
      transferase (TdT) to this sensor design, both the sensitivity and selectivity
      have been significantly enhanced. This DNA sensor achieves an impressive
      detection limit of 20 fM for a DNA sequence with 22 nucleotides, which is lower
      than that of an analogous optical DNA sensor by 2 orders of magnitude. More
      importantly, it exhibits excellent selectivity against even a single-base
      mismatched sequence. In addition, this novel DNA sensor presents reliable
      reusability and is capable of measuring target DNA in complex matrixes, such as
      undiluted human serum, with minimal interference. These advantages make our E-IGT
      sensor a promising contender in the E-DNA sensor family for medical diagnostics. 

PMID- 25369557
TI  - Giving patients a starring role in their own care: a bibliometric analysis of the
      on-going literature debate.
AB  - BACKGROUND: Patient-centred care has been advocated as a key component of high
      quality patient care, yet its meanings and related actions have been difficult to
      ascertain. OBJECTIVE: To map the use of different terms related to the process of
      giving patients a starring role in their own care and clarify the possible
      boundaries between terms that are often mixed. METHODS: A literature search was
      conducted using different electronic databases. All records containing the search
      terms 'patient engagement', 'patient activation', 'patient empowerment', 'patient
      involvement', 'patient adherence', 'patient compliance' and 'patient
      participation' were collected. Identified literature was then analysed using the
      Statistical Package for Social Science (SPSS). The number of yearly publications,
      most productive countries, cross-concepts articles and various scientific fields
      dealing with the multidisciplinary concepts were identified. RESULTS: Overall, 58
      987 papers were analysed. Correspondence analysis revealed three temporal trends.
      The first period (2002-2004) focused on compliance and adherence, the second
      period (2006-2009) focused on the relationship between participation and
      involvement, and the third one (2010-2013) emphasized empowerment. Patient
      activation and patient engagement followed the temporal development trend
      connected to the 'immediate future'. DISCUSSION AND CONCLUSIONS: The bibliometric
      trend suggests that the role of patient in the health-care system is changing. In
      the last years, the patient was viewed as a passive receptor of medical
      prescription. To date, the need to consider patients as active partners of health
      care planning and delivery is growing. In particular, the term patient engagement
      appears promising, not only for its increasing growth of interest in the
      scholarly debate, but also because it offers a broader and better systemic
      conceptualization of the patients' role in the fruition of health care. To build
      a shared vocabulary of terms and concepts related to the active role of patients
      in the health-care process may be envisaged as the first operative step towards a
      concrete innovation of health-care organizations and systems.

PMID- 25369559
TI  - Few-layer black phosphorus field-effect transistors with reduced current
      fluctuation.
AB  - We investigated the reduction of current fluctuations in few-layer black
      phosphorus (BP) field-effect transistors resulting from Al2O3 passivation. In
      order to verify the effect of Al2O3 passivation on device characteristics,
      measurements and analyses were conducted on thermally annealed devices before and
      after the passivation. More specifically, static and low-frequency noise analyses
      were used in monitoring the charge transport characteristics in the devices. The
      carrier number fluctuation (CNF) model, which is related to the charge
      trapping/detrapping process near the interface between the channel and gate
      dielectric, was employed to describe the current fluctuation phenomena. Noise
      reduction due to the Al2O3 passivation was expressed in terms of the reduced
      interface trap density values D(it) and N(it), extracted from the subthreshold
      slope (SS) and the CNF model, respectively. The deviations between the interface
      trap density values extracted using the SS value and CNF model are elucidated in
      terms of the role of the Schottky barrier between the few-layer BP and metal
      contact. Furthermore, the preservation of the Al2O3-passivated few-layer BP
      flakes in ambient air for two months was confirmed by identical Raman spectra.

PMID- 25369560
TI  - Panchromatic enhancement of light-harvesting efficiency in dye-sensitized solar
      cells using thermally annealed Au@SiO2 triangular nanoprisms.
AB  - Plasmonic enhancement is an attractive method for improving the efficiency of dye
      sensitized solar cells (DSSCs). Plasmonic materials with sharp features, such as
      triangular metal nanoparticles, show stronger plasmonic effects than their
      spherical analogues; however, these nanoparticles are also often thermally
      unstable. In this work, we investigated the thermal stability of Au@SiO2
      triangular nanoprisms by annealing at different temperatures. Morphological
      changes were observed at temperatures greater than 250  degrees C, which resulted
      in a blue shift of the localized surface plasmon resonance (LSPR). Annealing at
      450  degrees C led to a further blue shift; however, this resulted in better
      overlap of the LSPR with the absorption spectrum of black dye. By introducing
      0.05% (w/w) Au@SiO2 nanoprisms into DSSCs, we were able to achieve a panchromatic
      enhancement of the light-harvesting efficiency. This led to a 15% increase in the
      power conversion efficiency from 3.9 +/- 0.6% to 4.4 +/- 0.4%. 

PMID- 25369558
TI  - The preventability of ventilator-associated events. The CDC Prevention Epicenters
      Wake Up and Breathe Collaborative.
AB  - RATIONALE: The CDC introduced ventilator-associated event (VAE) definitions in
      January 2013. Little is known about VAE prevention. We hypothesized that daily,
      coordinated spontaneous awakening trials (SATs) and spontaneous breathing trials
      (SBTs) might prevent VAEs. OBJECTIVES: To assess the preventability of VAEs.
      METHODS: We nested a multicenter quality improvement collaborative within a
      prospective study of VAE surveillance among 20 intensive care units between
      November 2011 and May 2013. Twelve units joined the collaborative and implemented
      an opt-out protocol for nurses and respiratory therapists to perform paired daily
      SATs and SBTs. The remaining eight units conducted surveillance alone. We
      measured temporal trends in VAEs using generalized mixed effects regression
      models adjusted for patient-level unit, age, sex, reason for intubation,
      Sequential Organ Failure Assessment score, and comorbidity index. MEASUREMENTS
      AND MAIN RESULTS: We tracked 5,164 consecutive episodes of mechanical
      ventilation: 3,425 in collaborative units and 1,739 in surveillance-only units.
      Within collaborative units, significant increases in SATs, SBTs, and percentage
      of SBTs performed without sedation were mirrored by significant decreases in
      duration of mechanical ventilation and hospital length-of-stay. There was no
      change in VAE risk per ventilator day but significant decreases in VAE risk per
      episode of mechanical ventilation (odds ratio [OR], 0.63; 95% confidence interval
      [CI], 0.42-0.97) and infection-related ventilator-associated complications (OR,
      0.35; 95% CI, 0.17-0.71) but not pneumonias (OR, 0.51; 95% CI, 0.19-1.3). Within
      surveillance-only units, there were no significant changes in SAT, SBT, or VAE
      rates. CONCLUSIONS: Enhanced performance of paired, daily SATs and SBTs is
      associated with lower VAE rates. Clinical trial registered with
      www.clinicaltrials.gov (NCT 01583413).

PMID- 25369561
TI  - Characterizing substrate selectivity of ubiquitin C-terminal hydrolase-L3 using
      engineered alpha-linked ubiquitin substrates.
AB  - The ubiquitin-proteasome system (UPS) is highly complex and entails the concerted
      actions of many enzymes that function to ubiquitinate proteins targeted to the
      proteasome as well as enzymes that remove and recycle ubiquitin for additional
      rounds of proteolysis. Ubiquitin C-terminal hydrolase-L3 (UCH-L3) is a human
      cytosolic deubiquitinase whose precise biological function is not known. It is
      believed to hydrolyze small peptides or chemical adducts from the C-terminus of
      ubiquitin that may be remnant from proteasomal processing. In addition, UCH-L3 is
      a highly effective biotechnological tool that is used to produce small or
      unstable peptides/proteins recalcitrant to production in Escherichia coli
      expression systems. Previous research, which explored the substrate selectivity
      of UCH-L3, demonstrated a substrate size limitation for proteins/peptides
      expressed as alpha-linked C-terminal fusions to ubiquitin and also suggested that
      an additional substrate property may affect UCH-L3 hydrolysis [ Larsen , C. N. et
      al. (1998) Biochemistry 37 , 3358 - 3368 ]. Using a series of engineered protein
      substrates, which are similar in size yet differ in secondary structure, we
      demonstrate that thermal stability is a key factor that significantly affects UCH
      L3 hydrolysis. In addition, we show that the thermal stabilities of the
      engineered substrates are not altered by fusion to ubiquitin and offer a possible
      mechanism as to how ubiquitin affects the structural and unfolding properties of
      natural in vivo targets. 

PMID- 25369562
TI  - Direct oxidative coupling of enamides and 1,3-dicarbonyl compounds: a facile and
      versatile approach to dihydrofurans, furans, pyrroles, and dicarbonyl enamides.
AB  - An efficient manganese(III)-mediated oxidative coupling reaction between alpha
      aryl enamides and 1,3-dicarbonyl compounds has been developed. A series of
      dihydrofurans and dicarbonyl enamides were synthesized in moderate to good
      yields. Moreover, these dihydrofurans could be readily transformed into the
      corresponding furans and pyrroles via the Paal-Knorr reaction. 

PMID- 25369563
TI  - Intramolecular oxyacylation of alkenes using a hydroxyl directing group.
AB  - Alkene oxyacylation is a new strategy for the preparation of beta-oxygenated
      ketones. Now, with Ir catalysis and low-cost salicylate esters, alkene
      oxyacylation can be promoted by simple and versatile hydroxyl directing groups.
      This paper discusses catalyst optimization, substituent effects, mechanistic
      experiments, and the challenges associated with asymmetric catalysis. Crossover
      experiments point to several key steps of the mechanism being reversible,
      including the most likely enantiodetermining steps. The oxyacylation products are
      also prone to racemization without catalyst when heated alone; however, crossover
      is not observed without catalyst. These observations account for the low levels
      of enantioinduction in alkene oxyacylation. The versatility of the hydroxyl
      directing group is highlighted by demonstrating further transformations of the
      products. 

PMID- 25369564
TI  - Synchronized mammalian cell culture: part II--population ensemble modeling and
      analysis for development of reproducible processes.
AB  - The consideration of inherent population inhomogeneities of mammalian cell
      cultures becomes increasingly important for systems biology study and for
      developing more stable and efficient processes. However, variations of cellular
      properties belonging to different sub-populations and their potential effects on
      cellular physiology and kinetics of culture productivity under bioproduction
      conditions have not yet been much in the focus of research. Culture heterogeneity
      is strongly determined by the advance of the cell cycle. The assignment of cell
      cycle specific cellular variations to large-scale process conditions can be
      optimally determined based on the combination of (partially) synchronized
      cultivation under otherwise physiological conditions and subsequent population
      resolved model adaptation. The first step has been achieved using the physical
      selection method of countercurrent flow centrifugal elutriation, recently
      established in our group for different mammalian cell lines which is presented in
      Part I of this paper series. In this second part, we demonstrate the successful
      adaptation and application of a cell-cycle dependent population balance ensemble
      model to describe and understand synchronized bioreactor cultivations performed
      with two model mammalian cell lines, AGE1.HNAAT and CHO-K1. Numerical adaptation
      of the model to experimental data allows for detection of phase-specific
      parameters and for determination of significant variations between different
      phases and different cell lines. It shows that special care must be taken with
      regard to the sampling frequency in such oscillation cultures to minimize phase
      shift (jitter) artifacts. Based on predictions of long-term oscillation behavior
      of a culture depending on its start conditions, optimal elutriation setup trade
      offs between high cell yields and high synchronization efficiency are proposed.

PMID- 25369565
TI  - Acyclic cucurbit[n]uril-type molecular containers: influence of aromatic walls on
      their function as solubilizing excipients for insoluble drugs.
AB  - We studied the influence of the aromatic sidewalls on the ability of acyclic
      CB[n]-type molecular containers (1a-1e) to act as solubilizing agents for 19
      insoluble drugs including the developmental anticancer agent PBS-1086. All five
      containers exhibit good water solubility and weak self-association (Ks <= 624 M(
      1)). We constructed phase solubility diagrams to extract Krel and Ka values for
      the container.drug complexes. The acyclic CB[n]-type containers generally display
      significantly higher Ka values than HP-beta-CD toward drugs. Containers 1a-1e
      bind the steroidal ring system and aromatic moieties of insoluble drugs. Compound
      1b displays highest affinity toward most of the drugs studied. Containers 1a and
      1b are broadly applicable and can be used to formulate a wider variety of
      insoluble drugs than was previously possible with cyclodextrin technology. For
      drugs that are solubilized by both HP-beta-CD and 1a-1e, lower concentrations of
      1a-1e are required to achieve identical [drug]. 

PMID- 25369566
TI  - Central nervous system complications after liver transplantation: common but
      mostly transient phenomena.
AB  - Although central nervous system complications (CNSCs) are common after orthotopic
      liver transplantation (OLT), standardized prospective studies are still lacking.
      This prospective study was aimed at determining the incidence of CNSCs,
      describing their clinical presentations, and establishing predicting factors. One
      hundred thirty-six adult patients who underwent OLT at Hannover Medical School
      between December 2008 and June 2011 were included. Weekly examinations were
      performed by a neurologist during the hospital stay after OLT. Patient data,
      donor data, and operative and postoperative variables were collected. Patients
      with cerebral dysfunction after OLT underwent a diagnostic work-up, which
      included brain imaging and, if necessary, cerebrospinal fluid analysis. Patients
      with central nervous system (CNS) symptoms but negative imaging and cerebrospinal
      fluid results and patients with pontine myelinolysis or posterior reversible
      encephalopathy syndrome were placed in a metabolic-toxic CNSC group, and patients
      with strokes, intracranial hemorrhaging, or CNS infections were placed in a
      nonmetabolic CNSC group. Multiple regression analysis was used to identify
      independent risk factors for the development of metabolic-toxic CNSCs. After
      excluding two patients that died after OLT without regaining consciousness, forty
      four (32.8%) patients developed CNSCs: 37 of these patients (27.6%) had metabolic
      toxic CNSCs, and 7 (5.2%) had nonmetabolic CNSCs. Acute-on-chronic liver failure,
      the number of subsequent surgeries, and primary sclerosing cholangitis were
      identified as independent predictors for the development of metabolic-toxic
      CNSCs. Metabolic-toxic CNSCs were associated with prolonged hospital stays, and
      nonmetabolic CNSCs were associated with higher mortality. In conclusion, CNSCs
      are common and relevant complications after OLT. Patients after OLT, especially
      with risk factors, should undergo a regular standardized neurological examination
      that would allow early detection of these complications.

PMID- 25369567
TI  - Predictors of 30 day hospital readmission in patients with type 2 diabetes: a
      retrospective, case-control, database study.
AB  - OBJECTIVE: To assess factors predictive of all-cause, 30 day hospital readmission
      among patients with type 2 diabetes in the United States. METHODS: A
      retrospective, case-control study using deidentified Humedica electronic health
      record data was conducted to identify patients >=18 years old with >=6 months of
      data prior to index hospitalization (pre-period) and >=30 days of data after
      discharge (post-period). Combined methods of bootstrap resampling and stepwise
      logistic regression were used to identify factors associated with readmission.
      RESULTS: Among 52,070 patients with type 2 diabetes and an initial
      hospitalization for any reason, 5201 (10.0%) patients were readmitted within 30
      days and 46,869 (90.0%) patients showed no evidence of readmission. Diabetic
      treatment escalation; race; type 2 diabetes diagnosis prior to the index stay;
      pre-period heart failure; and number of pre-period, inpatient healthcare visits
      were among the strongest predictors of 30 day readmission. From a receiver
      operating characteristic plot (mean area under curve of 0.693), the predictive
      accuracy of the final logistic regression model is considered modest. This result
      might be due to the unavailability of some variables or data. CONCLUSIONS: These
      results highlight the importance of the appropriate recognition of and treatment
      for type 2 diabetes, prior to and during hospitalization and following discharge,
      in order to impact a subsequent hospitalization. In our analysis, escalation of
      diabetic treatments (especially those escalated from having no records of anti
      diabetic medications to treatment with insulin) was the strongest predictor of 30
      day readmission. Limitations of this study include the fact that hospitalizations
      and other encounters, outside the Humedica network, were not captured in this
      analysis.

PMID- 25369568
TI  - Comparing vegetation types and anthropic disturbance levels in the Atlantic
      forest: how do Pentatomoidea (Hemiptera: Heteroptera) assemblages respond?
AB  - The Atlantic Forest (AF) is considered the most fragmented and endangered
      Brazilian biome. The diversity of phytophagous insects increases after
      disturbances in forests, and it was hypothesized the Pentatomidae can furnish
      ecologically reliable information in terms of diversity in response to the
      changes occurring in AF. Our aim was to quantify the response of assemblages of
      Pentatomoidea to gradient of human disturbance in two vegetation types of the AF
      dense ombrophilous forest (DOF) and mixed ombrophilous forest (MOF). Twelve
      transects were grouped into environmental classes, namely open, intermediate, and
      closed. Overall, 1,017 pentatomoids were sampled, representing 64 species. The
      open environment was more abundant than closed environment, though it is expected
      that Pentatomoidea respond with increasing abundance when under light or moderate
      disturbance. The MOF was more abundant than DOF, and the composition differed
      between both of them. Given the differences in composition between MOF and DOF,
      abiotic variables are important factors acting as environmental filters for
      Pentatomoidea, not just directly on the insects, but probably also on the
      nutritional support of their host plants. 

PMID- 25369569
TI  - Maltreatment of children.

PMID- 25369570
TI  - School refusal and online high school.

PMID- 25369571
TI  - A 15-year-old male with pain and numbness in his right foot.

PMID- 25369572
TI  - "Nailing" the management of the ingrown great toenail.
AB  - "Nailing" the management of the severely ingrown great toenail, commonly
      encountered in the adolescent population, is an important tool in the
      pediatrician's armamentarium. I have found great toenail removal to be
      worthwhile, with straightforward indications; and quite rewarding for my patients
      in terms of time, convenience, and costs. The key to the procedure is to keep it
      simple. Four basic vital steps are involved: (1) operative permit and
      explanation; (2) performing a careful complete digital nerve block; (3) removing
      the entire toenail; and, importantly, (4) performing a partial chemical
      matricectomy--with readily available silver nitrate sticks--to prevent frequent
      recurrences.

PMID- 25369573
TI  - A 9-year-old female with bilateral leg weakness after influenza vaccination.

PMID- 25369574
TI  - A 10-week-old female with fever and an inability to move her left leg.

PMID- 25369575
TI  - Child neglect.

PMID- 25369576
TI  - Supraventricular tachycardia in infancy and childhood.
AB  - Supraventricular tachycardia (SVT) is the most common arrhythmia in the pediatric
      population. Despite its commonality, presentation of SVT can be nonspecific and
      varies based upon age with infants demonstrating fussiness or irritability and
      older children reporting vague perceptions of tachycardia or palpitations.
      Furthermore, SVT may manifest as self-limited paroxysms or with prolonged runs of
      SVT with subsequent development of cardiac dysfunction, heart failure, and
      multiorgan shock. Clinicians must maintain high levels of suspicion for SVT given
      the potentially dire consequences of untreated SVT. When diagnosed, there are
      effective acute and chronic treatments for SVT, with potential for spontaneous
      resolution in many infants.

PMID- 25369577
TI  - Medical neglect.
AB  - Medical neglect occurs when children are harmed or placed at significant risk of
      harm by gaps in their medical care. This is most likely to occur and to be
      recognized when families lack resources, commonly due to poverty, and when
      medical demands are high, such as with complex, severe, and chronic illness. A
      systematic evaluation of the probabilities for harm from gaps in care versus
      benefits from improved care will define medical neglect. A broad consideration of
      child, family, community, and medical system contributions to identified gaps
      will guide management. Special circumstances, such as lapsed immunizations,
      unremitting obesity, and medically motivated alterations in care, are often
      challenging for medical providers. Guidance for these specific situations is
      available from the American Academy of Pediatrics, and from the medical
      literature.

PMID- 25369578
TI  - Adequate supervision for children and adolescents.
AB  - Primary care providers (PCPs) have the opportunity to improve child health and
      well-being by addressing supervision issues before an injury or exposure has
      occurred and/or after an injury or exposure has occurred. Appropriate
      anticipatory guidance on supervision at well-child visits can improve supervision
      of children, and may prevent future harm. Adequate supervision varies based on
      the child's development and maturity, and the risks in the child's environment.
      Consideration should be given to issues as wide ranging as swimming pools, falls,
      dating violence, and social media. By considering the likelihood of harm and the
      severity of the potential harm, caregivers may provide adequate supervision by
      minimizing risks to the child while still allowing the child to take "small"
      risks as needed for healthy development. Caregivers should initially focus on
      direct (visual, auditory, and proximity) supervision of the young child.
      Gradually, supervision needs to be adjusted as the child develops, emphasizing a
      safe environment and safe social interactions, with graduated independence. PCPs
      may foster adequate supervision by providing concrete guidance to caregivers. In
      addition to preventing injury, supervision includes fostering a safe, stable, and
      nurturing relationship with every child. PCPs should be familiar with
      age/developmentally based supervision risks, adequate supervision based on those
      risks, characteristics of neglectful supervision based on age/development, and
      ways to encourage appropriate supervision throughout childhood.

PMID- 25369580
TI  - The Safe Environment for Every Kid model: promotion of children's health,
      development, and safety, and prevention of child neglect.
AB  - Child neglect is by far the most prevalent form of child maltreatment. There is a
      need to try to prevent this problem, and pediatric primary care offers an
      excellent opportunity. This article describes one such approach, the Safe
      Environment for Every Kid (SEEK) model. SEEK enables practitioners to identify
      and help address psychosocial problems facing many families. These include
      parental depression, substance abuse, major stress, intimate partner violence,
      harsh punishment, and food insecurity--problems that have been associated with
      neglect. Two large randomized, controlled trials yielded promising findings.
      Materials are now available to help practitioners implement this evidence-based
      practical model, thereby enhancing the primary care provided to children and
      their families.

PMID- 25369579
TI  - Nutritional and growth issues related to child neglect.
AB  - Child neglect and obesity are major public health problems that undermine
      children's health and contribute to lifelong disparities. Most of the past
      research has focused on relations between child neglect and failure to thrive.
      This article finds that evidence linking child neglect with obesity is mixed. In
      a recent meta-analysis, five of the eight studies reviewed did not find an
      increased risk of obesity among neglected children. The case study and three
      longitudinal studies that reported a relationship between neglect and obesity
      were conducted among young children, and used caregiver or teacher/clinician
      definitions of neglect, rather than referrals to state protective service
      agencies. Dysregulation of the neuroendocrine system associated with neglect has
      been implicated, but further research is needed to understand the mechanisms that
      may increase children's risk for obesity. Findings suggest that under some
      conditions neglect may increase the risk for excessive weight gain, and that high
      body mass index may be an indicator of possible neglect. By exploring both
      possibilities, clinicians can promote children's healthy growth and development
      and prevent subsequent health disparities.

PMID- 25369581
TI  - Advocacy and child neglect.
AB  - Pediatricians have a unique opportunity to intervene in the lives of children to
      identify and to prevent neglect. While it remains important to care for
      individual patients affected by neglect, the ecological model of child neglect
      requires intervention at the parent, family, community, and societal levels.
      Pediatricians can improve the outcomes for children by advocating for policies
      and interventions at each level. Effective advocacy principally requires the
      willingness to tackle broader issues beyond individual clinical care. Working
      with local, state, and national organizations, pediatricians can contribute a
      unified voice to promote evidence-based policies and programs that improve the
      well-being of children.

PMID- 25369582
TI  - The prevalence of uncontrolled pain in long-term care: a pilot study examining
      outcomes of pain management processes.
AB  - Pain in long-term care (LTC) is common among older residents despite the vast
      options available for optimal pain management. Inadequate pain management affects
      individual health care outcomes. Researcher evidence has shown that nurse
      practitioners (NPs) improve the quality of care in LTC but are challenged by
      multiple barriers that inhibit optimal pain control. The purpose of the current
      pilot study was to explore both the pain management processes used by nurses in
      LTC and the documented patient outcomes that come from these processes. In
      addition, factors were identified that may impact the NP role in providing
      adequate pain control in LTC. This descriptive study used a retrospective, case
      controlled research design that incorporated reviewing 55 LTC resident medical
      records. Results show how the process of pain management in LTC can be improved
      by expanding the professional role of the NP.

PMID- 25369583
TI  - Preferred computer activities among individuals with dementia: a pilot study.
AB  - Computers offer new activities that are easily accessible, cognitively
      stimulating, and enjoyable for individuals with dementia. The current descriptive
      study examined preferred computer activities among nursing home residents with
      different severity levels of dementia. A secondary data analysis was conducted
      using activity observation logs from 15 study participants with dementia (severe
      = 115 logs, moderate = 234 logs, and mild = 124 logs) who participated in a
      computer activity program. Significant differences existed in preferred computer
      activities among groups with different severity levels of dementia. Participants
      with severe dementia spent significantly more time watching slide shows with
      music than those with both mild and moderate dementia (F [2,12] = 9.72, p =
      0.003). Preference in playing games also differed significantly across the three
      groups. It is critical to consider individuals' interests and functional
      abilities when computer activities are provided for individuals with dementia. A
      practice guideline for tailoring computer activities is detailed.

PMID- 25369584
TI  - Depression in older women with metastatic breast cancer.
AB  - Depressive symptoms are common in older women with late-stage breast cancer, and
      some of these patients meet criteria for major depressive disorder. Significant
      overlap exists among many of the most prevalent physical signs and symptoms of
      depression in older adults (e.g., weight loss, fatigue) and the physical signs
      and symptoms of malignancy or treatment for malignancy, which may contribute to
      ongoing underdiagnosis and undertreatment of depression in this population. The
      National Comprehensive Cancer Network and evidence-based geriatric nursing
      guidelines call for routine screening for depression with valid and reliable
      screening instruments among high-risk groups at every encounter. Geriatrics,
      oncology, and palliative care nurses are encouraged to regularly screen older
      women with metastatic breast cancer for depressive symptoms and maintain a low
      threshold for initiation of behavioral and/or psychopharmacological
      interventions.

PMID- 25369585
TI  - Behavioral and psychological symptoms of dementia: how long does every behavior
      last, and are particular behaviors associated with PRN antipsychotic agent use?
AB  - Behavioral and psychological symptoms of dementia (BPSD) affect approximately all
      residents in nursing homes at some point; however, the course of BPSD among this
      group is not well known. The goal of the current study was to describe the course
      of each measured BPSD over a period of 6 months. A secondary explorative
      objective was to identify which BPSD are associated with as-needed (PRN)
      antipsychotic drug use. This secondary analysis study of 146 nursing home
      residents was drawn from a prospective, observational, multisite (N = 7) cohort
      study. Results showed that BPSD lasted for an average of 2.3 months, and the BPSD
      saying things that do not make sense had the longest duration, with 3.6 months.
      PRN antipsychotic drug administration was associated with nocturnal BPSD and
      requesting help unnecessarily. Within 3 months, most BPSD were resolved by usual
      care; use of PRN antipsychotic medication was not associated with behaviors that
      put the residents or their caregivers at risk.

PMID- 25369586
TI  - Indications for platelet transfusion in patients with thrombocytopenia.

PMID- 25369587
TI  - Autologous plasma rich in growth factors in the prevention of severe bleeding
      after teeth extractions in patients with bleeding disorders: a controlled
      comparison with fibrin glue.
AB  - BACKGROUND: Dental extractions in haemophiliacs may cause secondary bleeding,
      requiring repeated surgical and haematological interventions. As a local
      haemostatic, fibrin glue has recognised efficacy but, as a plasma-derived
      product, it carries the risk of viral infections. We, therefore, compared fibrin
      glue with an autologous haemostatic, plasma rich in growth factors (PRGF), in a
      controlled trial. MATERIAL AND METHODS: One hundred and twenty patients with
      different blood disorders were randomised into two cohorts to undergo dental
      extraction procedures without hospitalisation. Prior to the extractions, patients
      underwent systemic haematological treatment. Complications were defined as
      secondary bleeding after the 7-day follow-up period or protracting after the
      repair procedure. RESULTS: There were 106 extractions (7 retained 3(rd) molars)
      in the group managed with fibrin glue: secondary bleeding affected 3/60 patients
      (5%) on the third day after extraction and necessitated additional surgery and
      systemic treatment (in one case the procedure had to be repeated on the 7(th)
      day). In the PRGF arm there were 98 extractions (23 retained 3(rd) molars):
      secondary bleeding affected two patients (3.3%) on the first day after extraction
      and was arrested with surgery without systemic treatment. Four out of the five
      secondary bleeds occurred in patients with haemophilia A. Concomitant diabetes or
      liver disease significantly increased the bleeding risk. DISCUSSION: The bleeding
      rates in the study and control arm prove that PRGF works as well as fibrin glue
      as a local haemostatic. Further assets are that PRGF has autologous origin, does
      not require additional systemic treatment in post-extraction repair surgery, is
      associated with an earlier onset of neo-angiogenesis and, overall, can reduce
      patients' distress and costs to the health system.

PMID- 25369589
TI  - In vitro evaluation of platelet concentrates suspended in additive solution and
      treated for pathogen reduction: effects of clumping formation.
AB  - BACKGROUND: Platelet concentrates may demonstrate visual, macroscopic clumps
      immediately after collection following aphaeresis or production from whole blood,
      independently of the preparation method or equipment used. The relationship
      between the occurrence of clumping and their effect on in vitro quality of
      platelets was investigated. MATERIAL AND METHODS: Platelet concentrates,
      suspended in SSP+ additive solution (Macopharma), were obtained by automated
      processing and also from routine processing. A total of twelve units were
      allocated to the test group (n=12) due to the presence of clumps. Platelet
      concentrates without clumps were used as controls (n=10). All platelet units were
      treated for pathogen reduction following storage under continuous agitation for
      in vitro testing over a 9-day storage period. RESULTS: No significant differences
      were found throughout storage between the groups. The lactate dehydrogenase
      levels increased in both groups; this increase was higher in the test group on
      the last day of testing, without there being a significant difference on day 2.
      In contrast, pH values on day 2 were significantly different between the test and
      control groups. Platelet-derived cytokines increased comparably during storage.
      DISCUSSION: The results confirm good in vitro quality and storage stability of
      platelets suspended in SSP+ and treated with the Intercept pathogen reduction
      system. The presence of "non-compacted" clumps in platelet concentrates does not
      appear to affect the in vitro quality of the platelets.

PMID- 25369588
TI  - Detection of microparticles from human red blood cells by multiparametric flow
      cytometry.
AB  - BACKGROUND: During storage, red blood cells (RBC) undergo chemical and
      biochemical changes referred to as "storage lesions". These events determine the
      loss of RBC integrity, resulting in lysis and release of microparticles. There is
      growing evidence of the clinical importance of microparticles and their role in
      blood transfusion-related side effects and pathogen transmission. Flow cytometry
      is currently one of the most common techniques used to quantify and characterise
      microparticles. Here we propose multiparametric staining to monitor and quantify
      the dynamic release of microparticles by stored human RBC. MATERIAL AND METHODS:
      RBC units (n=10) were stored under blood bank conditions for up to 42 days.
      Samples were tested at different time points to detect microparticles and
      determine the haemolysis rate (HR%). Microparticles were identified by flow
      cytometry combining carboxyfluorescein diacetate succinimidyl ester (CFSE) dye,
      annexin V and anti-glycophorin A antibody. RESULTS: We demonstrated that CFSE can
      be successfully used to label closed vesicles with an intact membrane. The
      combination of CFSE and glycophorin A antibody was effective for monitoring and
      quantifying the dynamic release of microparticles from RBC during storage. Double
      staining with CFSE/glycophorin A was a more precise approach, increasing vesicle
      detection up to 4.7-fold vs the use of glycophorin A/annexin V alone. Moreover,
      at all the time points tested, we found a robust correlation (R=0.625; p=0.0001)
      between HR% and number of microparticles detected. DISCUSSION: Multiparametric
      staining, based on a combination of CFSE, glycophorin A antibody and annexin V,
      was able to detect, characterise and monitor the release of microparticles from
      RBC units during storage, providing a sensitive approach to labelling and
      identifying microparticles for transfusion medicine and, more broadly, for cell
      based therapies.

PMID- 25369590
TI  - Diagnosis and management of severe congenital factor XIII deficiency in the
      Emergency Department: lessons from a "model" family.

PMID- 25369591
TI  - Participation of people with haemophilia in clinical trials of new treatments: an
      investigation of patients' motivations and existing barriers.
AB  - BACKGROUND: Over the last 50 years, clinical research investigating new
      treatments has been transforming the care of patients with haemophilia but we
      still have a long way to go and most clinical investigators are facing
      difficulties in recruiting appropriate candidates. A survey was conducted to
      evaluate what motivates people with haemophilia to participate in clinical
      research and to identify factors that might influence their willingness to
      participate. MATERIAL AND METHODS: A specific questionnaire concerning motivation
      and barriers to participation in clinical trials was sent to 135 adults with
      haemophilia. A classification tree was used to identify predictors of willingness
      to participate. RESULTS: Sixty-two patients returned the completed questionnaire,
      of whom 51 declared a potential willingness to participate in a clinical trial,
      although many were concerned about the new treatments' possible side effects or
      about time away from work. Predictors of willingness to participate were
      evaluated using a classification tree and four groups were established. Group 1
      comprised patients aged <=45 years old. Group 2 comprised patients>45 years old
      who reported having no knowledge of clinical research modalities. The two other
      groups comprised patients>45 years old who reported having some knowledge of
      clinical research modalities, with group 3 being <=59 years old and group 4 being
      >59 years old. The rate of willingness to participate was 96.6%, 28.6%, 70.6% and
      100.0%, respectively. DISCUSSION: The rate of willingness to participate in
      clinical research was significantly lower in patients who reported having no
      knowledge of clinical trial modalities, highlighting the relevance of providing
      improved knowledge about the modalities, risks, and benefits of clinical research
      to enhance participation in haemophilia trials.

PMID- 25369592
TI  - Erythroexchange in sickle cell disease. A three-step procedure to remove more
      haemoglobin S.

PMID- 25369593
TI  - Correction of knee flexion contracture at the time of surgical fixation of a
      femoral supracondylar fracture in a haemophiliac with inhibitors.

PMID- 25369595
TI  - Prevention of surgical delays by pre-admission type and screen in patients with
      scheduled surgical procedures: improved efficiency.

PMID- 25369594
TI  - Blood group distribution and life-expectancy: a single-centre experience.

PMID- 25369596
TI  - Comment on "Applying molecular immunohaematology to regularly transfused
      thalassaemic patients in Thailand".

PMID- 25369597
TI  - Thromboelastometry-guided therapy of massive gastrointestinal bleeding in a 12
      year old boy with severe Graft-versus-Host disease.

PMID- 25369598
TI  - In vitro evaluation of pathogen-inactivated buffy coat-derived platelet
      concentrates during storage: psoralen-based photochemical treatment step-by-step.
AB  - BACKGROUND: The Intercept Blood SystemTM (Cerus) is used to inactivate pathogens
      in platelet concentrates (PC). The aim of this study was to elucidate the extent
      to which the Intercept treatment modifies the functional properties of platelets.
      MATERIAL AND METHODS: A two-arm study was conducted initially to compare buffy
      coat-derived pathogen-inactivated PC to untreated PC (n=5) throughout storage. A
      four-arm study was then designed to evaluate the contribution of the compound
      adsorbing device (CAD) and ultraviolet (UV) illumination to the changes observed
      upon Intercept treatment. Intercept-treated PC, CAD-incubated PC, and UV
      illuminated PC were compared to untreated PC (n=5). Functional characteristics
      were assessed using flow cytometry, hypotonic shock response (HSR), aggregation,
      adhesion assays and flow cytometry for the detection of CD62P, CD42b, GPIIb-IIIa,
      phosphatidylserine exposure and JC-1 aggregates. RESULTS: Compared to fresh
      platelets, end-of-storage platelets exhibited greater passive activation,
      disruption of the mitochondrial transmembrane potential (Deltapsim), and
      phosphatidylserine exposure accompanied by a decreased capacity to respond to
      agonist-induced aggregation, lower HSR, and CD42b expression. The Intercept
      treatment resulted in significantly lower HSR and CD42b expression compared to
      controls on day 7, with no significant changes in CD62P, Deltapsim, or
      phosphatidylserine exposure. GPIIbIIIa expression was significantly increased in
      Intercept-treated platelets throughout the storage period. The agonist-induced
      aggregation response was highly dependent on the type and concentration of
      agonist used, indicating a minor effect of the Intercept treatment. The CAD and
      UV steps alone had a negligible effect on platelet aggregation. DISCUSSION: The
      Intercept treatment moderately affects platelet function in vitro. CAD and UV
      illumination alone make negligible contributions to the changes in aggregation
      observed in Intercept-treated PC.

PMID- 25369600
TI  - Complement-binding donor epitope sharing antibodies in a kidney transplant
      recipient.

PMID- 25369599
TI  - Classic and alternative red blood cell storage strategies: seven years of "
      omics" investigations.

PMID- 25369601
TI  - Controversies regarding the use of antithrombin for sepsis-associated
      disseminated intravascular coagulation: an update of the evidence.

PMID- 25369602
TI  - Preliminary evaluation of cord blood platelet gel for the treatment of skin
      lesions in children with dystrophic epidermolysis bullosa.

PMID- 25369603
TI  - Serodetection of Dengue virus and its antibodies among blood donors in the
      western region of Saudi Arabia: a preliminary study.

PMID- 25369604
TI  - Structural modification of H histo-blood group antigen.

PMID- 25369605
TI  - Red blood cell alloimmunisation in 18 to 50-year old transfused women: a 3-year
      study.

PMID- 25369607
TI  - Integration in groups of donors may modify attitudes towards blood donation.

PMID- 25369606
TI  - Angiopoietins in haematopoietic stem cell mobilisation in patients with
      haematological malignancies.
AB  - BACKGROUND: The bone marrow niche contains different types of cells including
      osteoblasts and endothelial progenitors, all of which interact and take part in
      the process of mobilisation. The aim of our study was to evaluate the levels of
      cytokines (osteopontin and angiopoietins 1 and 2) active in the bone marrow niche
      during the mobilisation of haematopoietic stem cells for autologous
      transplantation. MATERIALS AND METHODS: Forty-eight patients (24 females, 24
      males), median age 56.5 years, entered the study. The group consisted of patients
      with multiple myeloma (n=34), lymphoma (n=13) and acute myeloid leukaemia (n=1).
      Blood samples were collected before chemotherapy and on the day of the first
      apheresis. Cytokines were evaluated by enzyme-linked immunosorbent assays.
      Additionally, circulating endothelial cells were assessed by flow cytometry.
      RESULTS: The median concentration of angiopoietin 1 at the time of apheresis was
      lower than that at baseline (2.7 vs 7.8 ng/mL, p<0.001). In contrast, the median
      level of angiopoietin 2 increased during the mobilisation procedure (3.6 vs 2.8
      ng/mL, p=0.001). The patients were divided according to the number of days of
      granulocyte colony-stimulating factor treatment before the first apheresis into
      "early" (<median=11 days) and "late" (>median) mobilisers. The group of "early
      mobilisers" had higher baseline angiopoietin 1 levels (median=11.6 ng/mL) than
      those of the "late mobilisers" (median=6.0 ng/mL, p=0.05). An adverse correlation
      was observed between duration of granulocyte colony-stimulating factor treatment
      and baseline angiopoietin 1 level. Baseline angiopoietin 1 levels correlated with
      numbers of circulating endothelial cells. Low angiopoietin 2 level increased the
      chance of poor mobilisation. CONCLUSIONS: The angiogenic processes can influence
      the timing of mobilisation. Angiopoietins 1 and 2 need further evaluation in the
      context of mobilisation.

PMID- 25369608
TI  - Fibrinogen concentrate as first-line therapy in aortic surgery reduces
      transfusion requirements in patients with platelet counts over or under
      100*10(9)/L.
AB  - BACKGROUND: Administration of fibrinogen concentrate, targeting improved maximum
      clot firmness (MCF) of the thromboelastometric fibrin-based clot quality test
      (FIBTEM) is effective as first-line haemostatic therapy in aortic surgery. We
      performed a post-hoc analysis of data from a randomised, placebo-controlled trial
      of fibrinogen concentrate, to investigate whether fibrinogen concentrate reduced
      transfusion requirements for patients with platelet counts over or under
      100*10(9)/L. MATERIAL AND METHODS: Aortic surgery patients with coagulopathic
      bleeding after cardiopulmonary bypass were randomised to receive either
      fibrinogen concentrate (n=29) or placebo (n=32). Platelet count was measured upon
      removal of the aortic clamp, and coagulation and haematology parameters were
      measured peri-operatively. Transfusion of allogeneic blood components was
      recorded and compared between groups. RESULTS: After cardiopulmonary bypass,
      haemostatic and coagulation parameters worsened in all groups; plasma fibrinogen
      level (determined by the Clauss method) decreased by 43-58%, platelet count by 53
      64%, FIBTEM maximum clot firmness (MCF) by 38-49%, FIBTEM maximum clot elasticity
      (MCE) by 43-54%, extrinsically activated test (EXTEM) MCF by 11-22%, EXTEM MCE by
      25-41% and the platelet component of the clot by 23-39%. Treatment with
      fibrinogen concentrate (mean dose 7-9 g in the 4 groups) significantly reduced
      post-operative allogeneic blood component transfusion requirements when compared
      to placebo both for patients with a platelet count>=100*10(9)/L and for patients
      with a platelet count<100*10(9)/L. DISCUSSION: FIBTEM-guided administration of
      fibrinogen concentrate reduced transfusion requirements when used as a first-line
      haemostatic therapy during aortic surgery in patients with platelet counts over
      or under 100*10(9)/L.

PMID- 25369609
TI  - Evaluation of various methods of point-of-care testing of haemoglobin
      concentration in blood donors.
AB  - BACKGROUND: Point-of-care testing (POCT) devices for determining pre-donation
      haemoglobin (Hb) concentrations mark the advent of advanced technology for blood
      banks. POCT devices have undergone several improvements including changes in
      testing methodology and size of device, befitting the needs of blood donors and
      blood banks in terms of safety and quality of blood components. This study was
      planned to evaluate the suitability of non-invasive and invasive POCT devices for
      blood donor Hb screening. MATERIAL AND METHODS: Pre-donation Hb in apparently
      healthy blood donors was measured by a non-invasive spectrophotometric based
      method (NBM-200, OrSense) and an invasive method utilizing reagent free cuvettes
      (DiaSpect) along with a device using sodium azide-coated cuvettes (HemoControl,
      EKF diagnostic GmbH). The performance of the devices was evaluated by comparison
      with the reference method, i.e. an automated cell counter (KX-21). RESULTS: Hb
      was measured in 485 prospective blood donors. DiaSpect hemoglobin T system was
      found to be the most sensitive method of POCT for Hb (sensitivity 98.1%) followed
      by HemoControl (sensitivity 86.8%). NBM-200 was the least sensitive method
      (sensitivity 71.7%). The intraclass correlation coefficient was highest for
      DiaSpect (0.78), followed by HemoControl (0.77) and NBM-200 (0.43). The variation
      of results on repeat testing was high for NBM-200 with a coefficient of variation
      of 4.28%, compared to 2.19% for DiaSpect. On comparing the mean testing time,
      DiaSpect (1.9 seconds) was found to be significantly quicker than the other two
      POCT devices (p<0.001). DISCUSSION: NBM-200 has the apparent advantage of
      eliminating pain but also a substantial possibility of causing ineligible donors
      to be accepted. DiaSpect was fast and accurate, with its results showing perfect
      agreement with those of the standard method. It is, therefore, aptly suited for
      screening donors in blood banks.

PMID- 25369610
TI  - There is no change in soluble leucocyte selectin concentrations in whole blood
      after 48 hours of storage at 4  degrees C.

PMID- 25369612
TI  - Sensitivity of individual donor nucleic acid testing (NAT) for the detection of
      hepatitis B infection by studying diluted NAT yield samples.
AB  - BACKGROUND: Screening blood donors for the presence of hepatitis B virus surface
      antigen (HBsAg) has been the backbone of blood safety. However, occult hepatitis
      B infection (OBI) in donors can be missed when only HBsAg screening is used.
      Nucleic acid testing (NAT) is capable of detecting OBI among donors. The aim of
      our study was to analyse the sensitivity of NAT for detecting OBI. MATERIAL AND
      METHODS: The kits used during the study for serology testing were BioRad
      MonolisaTM HBsAg Ultra (HBsAg screening), Abbott Architect for anti-HBcAg (total)
      and anti-HBsAg testing, and Vitros(r) by Ortho Clinical Diagnostics for anti
      HBcAg (IgM). Procleix Ultrio was used for individual donor-NAT (ID-NAT) and
      Abbott m2000 for estimation of HBV DNA. Out of 28,134 HBsAg non-reactive donors,
      25 were ID-NAT-reactive. Of these 25 NAT yield samples, 18 were studied further
      at different dilutions from 1:2 to 1:16. The doubling dilutions were made with
      HBV non-reactive AB plasma. Undiluted samples were used for all serological tests
      and for HBV DNA estimation. RESULTS: Of the 18 samples studied, nine were NAT
      reactive at a dilution of <1:4 and five out of these showed presence of antibody
      to core antigen (IgG+IgM). Antibody to surface antigen was present in only two of
      the nine NAT-reactive samples, one with antibody to core antigen and the other
      without. Six had a viral load in the range from <10 to 38 IU/mL whereas the viral
      load in the remaining three samples was not determined. Among the other nine
      samples which were NAT-reactive at dilutions>=1:4, antibody to core antigen
      (IgG+IgM) was present in seven. DISCUSSION: Our study showed that ID-NAT testing
      along with HBsAg screening could detect most potentially HBV infectious donors
      (including those with OBI). NAT screening for HBV on diluted samples could
      compromise blood safety because samples with a low viral load will escape
      detection.

PMID- 25369614
TI  - Weak D in the Tunisian population.
AB  - BACKGROUND: More than 90 weak D types have been discovered to date. As there are
      no published data on the frequencies of weak D types in the Tunisian population,
      the aim of this study was to determine the composition of weak D alleles in our
      population. MATERIAL AND METHODS: Blood samples from 1777 D+ and 223 D- blood
      donors were tested for markers 809G, 1154C, 8G, 602G, 667G, 446A, and 885T
      relative to translation start codon by polymerase chain reaction with sequence
      specific primers to estimate the frequencies of weak D type 1, weak D type 2,
      weak D type 3, weak D type 4, weak D type 5 and weak D type 11 in our population.
      Twenty-three samples with positive reactions were re-evaluated by DNA sequencing
      of RHD exons 1-10 and adjacent intronic sequences. RESULTS: Among the D+ donor
      cohort, weak D type 4 was the most prevalent allele (n=33, 1.2%) followed by weak
      D type 2 (n=6, 0.17%), weak D type 1 (n=4, 0.11%), and weak D type 5 (n=1, 0.28%)
      and weak D type 11 (n=1, 0.28%). RHD sequencing identified a weak D type 4.0
      allele in all 19 samples tested. Among the D- pool, comprising 223 samples, we
      detected one sample with weak D type 4.0 associated with a C+c+E-e+ phenotype
      which had been missed by routine serological methods. DISCUSSION: Weak D type 4.0
      appears to be the most prevalent weak D in our population. However, all samples
      must be sequenced in order to determine the exact subtype of weak D type 4, since
      weak D type 4.2 has considerable clinical importance, being associated with anti
      D alloimmunisation. One case of weak D type 4 associated with dCe in trans had
      been missed by serology, so quality control of serological tests should be
      developed in our country.

PMID- 25369615
TI  - Fibrinogen concentrate as haemostatic therapy in acquired bleeding disorders: not
      only a question of dosing strategies and thresholds.

PMID- 25369611
TI  - Supportive care in patients with acute leukaemia: historical perspectives.

PMID- 25369617
TI  - Correction.

PMID- 25369613
TI  - Hepatitis E: an old infection with new implications.

PMID- 25369618
TI  - Consider thin basement membrane nephropathy as a possible cause of asymptomatic
      microscopic hematuria.

PMID- 25369616
TI  - The impact of external donor support through the U.S. President's Emergency Plan
      for AIDS Relief on the cost of red cell concentrate in Namibia, 2004-2011.
AB  - BACKGROUND: External assistance can rapidly strengthen health programmes in
      developing countries, but such funding can also create sustainability challenges.
      From 2004-2011, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR)
      provided more than $ 8 million to the Blood Transfusion Service of Namibia
      (NAMBTS) for supplies, equipment, and staff salaries. This analysis describes the
      impact that support had on actual production costs and the unit prices charged
      for red cell concentrate (RCC) units issued to public sector hospitals. MATERIAL
      AND METHODS: A costing system developed by NAMBTS to set public sector RCC unit
      prices was used to describe production costs and unit prices during the period of
      PEPFAR scale-up (2004-2009) and the 2 years in which PEPFAR support began to
      decline (2010-2011). Hypothetical production costs were estimated to illustrate
      differences had PEPFAR support not been available. RESULTS: Between 2004-2006,
      NAMBTS sold 22,575 RCC units to public sector facilities. During this time, RCC
      unit prices exceeded per unit cost-recovery targets by between 40.3% (US$ 16.75
      or N$ 109.86) and 168.3% (US$ 48.72 or N$ 333.28) per year. However, revenue
      surpluses dwindled between 2007 and 2011, the final year of the study period,
      when NAMBTS sold 20,382 RCC units to public facilities but lost US$23.31 (N$
      170.43) on each unit. DISCUSSION: PEPFAR support allowed NAMBTS to leverage
      domestic cost-recovery revenue to rapidly increase blood collections and the
      distribution of RCC. However, external support kept production costs lower than
      they would have been without PEPFAR. If PEPFAR funds had not been available, RCC
      prices would have needed to increase by 20% per year to have met annual cost
      recovery targets and funded the same level of investments as were made with
      PEPFAR support. Tracking the subsidising influence of external support can help
      blood services make strategic investments and plan for unit price increases as
      external funds are withdrawn.

PMID- 25369620
TI  - JNC 8: relaxing the standards.

PMID- 25369621
TI  - Safety of long-acting beta agonists in adults with asthma.

PMID- 25369622
TI  - Psychological therapies for chronic posttraumatic stress disorder.

PMID- 25369623
TI  - Diagnosis and management of ADHD in children.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral
      disorder in children, and the prevalence is increasing. Physicians should
      evaluate for ADHD in children with behavioral concerns (e.g., inattention,
      hyperactivity, impulsivity, oppositionality) or poor academic progress using
      validated assessment tools with observers from several settings (home, school,
      community) and self-observation, if possible. Physicians who inherit a patient
      with a previous ADHD diagnosis should review the diagnostic process, and current
      symptoms and treatment needs. Coexisting conditions (e.g., anxiety, learning,
      mood, or sleep disorders) should be identified and treated. Behavioral treatments
      are recommended for preschool-aged children and may be helpful at older ages.
      Effective behavioral therapies include parent training, classroom management, and
      peer interventions. Medications are recommended as first-line therapy for older
      children. Psychostimulants, such as methylphenidate and dextroamphetamine, are
      most effective for the treatment of core ADHD symptoms and have generally
      acceptable adverse effect profiles. There are fewer supporting studies for
      atomoxetine, guanfacine, and clonidine, and they are less effective than the
      psychostimulants. Height, weight, heart rate, blood pressure, symptoms, mood, and
      treatment adherence should be recorded at follow-up visits. 

PMID- 25369624
TI  - Dyspareunia in women.
AB  - Dyspareunia is recurrent or persistent pain with sexual activity that causes
      marked distress or interpersonal conflict. It affects approximately 10% to 20% of
      U.S. women. Dyspareunia can have a significant impact on a woman's mental and
      physical health, body image, relationships with partners, and efforts to
      conceive. The patient history should be taken in a nonjudgmental way and progress
      from a general medical history to a focused sexual history. An educational pelvic
      examination allows the patient to participate by holding a mirror while the
      physician explains normal and abnormal findings. This examination can increase
      the patient's perception of control, improve self-image, and clarify findings and
      how they relate to discomfort. The history and physical examination are usually
      sufficient to make a specific diagnosis. Common diagnoses include provoked
      vulvodynia, inadequate lubrication, postpartum dyspareunia, and vaginal atrophy.
      Vaginismus may be identified as a contributing factor. Treatment is directed at
      the underlying cause of dyspareunia. Depending on the diagnosis, pelvic floor
      physical therapy, lubricants, or surgical intervention may be included in the
      treatment plan. 

PMID- 25369625
TI  - Appropriate use of medical interpreters.
AB  - More than 25 million Americans speak English "less than very well," according to
      the U.S. Census Bureau. This population is less able to access health care and is
      at higher risk of adverse outcomes such as drug complications and decreased
      patient satisfaction. Title VI of the Civil Rights Act mandates that interpreter
      services be provided for patients with limited English proficiency who need this
      service, despite the lack of reimbursement in most states. Professional
      interpreters are superior to the usual practice of using ad hoc interpreters
      (i.e., family, friends, or untrained staff). Untrained interpreters are more
      likely to make errors, violate confidentiality, and increase the risk of poor
      outcomes. Children should never be used as interpreters except in emergencies.
      When using an interpreter, the clinician should address the patient directly and
      seat the interpreter next to or slightly behind the patient. Statements should be
      short, and the discussion should be limited to three major points. In addition to
      acting as a conduit for the discussion, the interpreter may serve as a cultural
      liaison between the physician and patient. When a bilingual clinician or a
      professional interpreter is not available, phone interpretation services or
      trained bilingual staff members are reasonable alternatives. The use of
      professional interpreters (in person or via telephone) increases patient
      satisfaction, improves adherence and outcomes, and reduces adverse events, thus
      limiting malpractice risk. 

PMID- 25369626
TI  - Effectiveness of outpatient case management for adults.

PMID- 25369627
TI  - Active duty soldier with punctate marks on the feet.

PMID- 25369628
TI  - Challenges and opportunities in the care of Asian American patients.

PMID- 25369629
TI  - To whipple or not: choices in cancer treatment.

PMID- 25369630
TI  - Oseltamivir slightly decreases influenza symptom duration but not
      hospitalizations.

PMID- 25369631
TI  - Physical therapy no better than sham therapy for hip osteoarthritis.

PMID- 25369632
TI  - No benefit to prolonged dual antiplatelet therapy after drug-eluting stent
      placement.

PMID- 25369633
TI  - JNC8 guidelines for the management of hypertension in adults.

PMID- 25369635
TI  - Identification of 'erasers' for lysine crotonylated histone marks using a
      chemical proteomics approach.
AB  - Posttranslational modifications (PTMs) play a crucial role in a wide range of
      biological processes. Lysine crotonylation (Kcr) is a newly discovered histone
      PTM that is enriched at active gene promoters and potential enhancers in
      mammalian cell genomes. However, the cellular enzymes that regulate the addition
      and removal of Kcr are unknown, which has hindered further investigation of its
      cellular functions. Here we used a chemical proteomics approach to
      comprehensively profile 'eraser' enzymes that recognize a lysine-4 crotonylated
      histone H3 (H3K4Cr) mark. We found that Sirt1, Sirt2, and Sirt3 can catalyze the
      hydrolysis of lysine crotonylated histone peptides and proteins. More
      importantly, Sirt3 functions as a decrotonylase to regulate histone Kcr dynamics
      and gene transcription in living cells. This discovery not only opens
      opportunities for examining the physiological significance of histone Kcr, but
      also helps to unravel the unknown cellular mechanisms controlled by Sirt3, that
      have previously been considered solely as a deacetylase. 

PMID- 25369636
TI  - The transcription factor FOXL2 mobilizes estrogen signaling to maintain the
      identity of ovarian granulosa cells.
AB  - FOXL2 is a lineage determining transcription factor in the ovary, but its direct
      targets and modes of action are not fully characterized. In this study, we
      explore the targets of FOXL2 and five nuclear receptors in murine primary
      follicular cells. We found that FOXL2 is required for normal gene regulation by
      steroid receptors, and we show that estrogen receptor beta (ESR2) is the main
      vector of estradiol signaling in these cells. Moreover, we found that FOXL2
      directly modulates Esr2 expression through a newly identified intronic element.
      Interestingly, we found that FOXL2 repressed the testis-determining gene Sox9
      both independently of estrogen signaling and through the activation of ESR2
      expression. Altogether, we show that FOXL2 mobilizes estrogen signaling to
      establish a coherent feed-forward loop repressing Sox9. This sheds a new light on
      the role of FOXL2 in ovarian maintenance and function. 

PMID- 25369637
TI  - Forward genetics for back-in-time questions.
AB  - A genetic screen has revealed one of the molecules that allow choanoflagellates,
      the closest unicellular relative of animals, to form colonies, which could help
      researchers to answer questions about the earliest days of animal evolution. 

PMID- 25369638
TI  - Increase in reported malaria cases prompts clarification regarding diagnosis and
      treatment.

PMID- 25369639
TI  - Glycemic control is an important consideration in diabetes care.

PMID- 25369641
TI  - Management of influenza in the 2014-2015 season: recommendations and limitations.

PMID- 25369642
TI  - Urinalysis: case presentations for the primary care physician.
AB  - Urinalysis is useful in diagnosing systemic and genitourinary conditions. In
      patients with suspected microscopic hematuria, urine dipstick testing may suggest
      the presence of blood, but results should be confirmed with a microscopic
      examination. In the absence of obvious causes, the evaluation of microscopic
      hematuria should include renal function testing, urinary tract imaging, and
      cystoscopy. In a patient with a ureteral stent, urinalysis alone cannot establish
      the diagnosis of urinary tract infection. Plain radiography of the kidneys,
      ureters, and bladder can identify a stent and is preferred over computed
      tomography. Asymptomatic bacteriuria is the isolation of bacteria in an
      appropriately collected urine specimen obtained from a person without symptoms of
      a urinary tract infection. Treatment of asymptomatic bacteriuria is not
      recommended in nonpregnant adults, including those with prolonged urinary
      catheter use. 

PMID- 25369643
TI  - Over-the-Counter Medications in Pregnancy.
AB  - Many pregnant women take over-the-counter (OTC) medications despite the absence
      of randomized controlled trials to guide their use during pregnancy. Most data
      come from case-control and cohort studies. In 1979, the U.S. Food and Drug
      Administration began reviewing all prescription and OTC medications to develop
      risk categories for use in pregnancy. Most OTC medications taken during pregnancy
      are for allergy, respiratory, gastrointestinal, or skin conditions, as well as
      for general analgesia. Acetaminophen, which is used by about 65% of pregnant
      women, is generally considered safe during any trimester. Cold medications are
      also commonly used and are considered safe for short-term use outside of the
      first trimester. Many gastrointestinal medications are now available OTC.
      Histamine H2 blockers and proton pump inhibitors have not demonstrated
      significant fetal effects. Nonsteroidal anti-inflammatory drugs are generally not
      recommended in pregnancy, especially during organogenesis and in the third
      trimester. There are even fewer data regarding use of individual herbal
      supplements. Ginger is considered safe and effective for treating nausea in
      pregnancy. Topical creams are considered safe based on small studies and previous
      practice. All OTC medication use should be discussed with patients, and the
      effects of the symptoms should be balanced with the risks and benefits of each
      medication. Because of the expanding OTC market, formalized studies are warranted
      for patients to make a safe and informed decision about OTC medication use during
      pregnancy. 

PMID- 25369644
TI  - Enuresis in children: a case based approach.
AB  - Enuresis is defined as intermittent urinary incontinence during sleep in a child
      at least five years of age. Approximately 5% to 10% of all seven-year-olds have
      enuresis, and an estimated 5 to 7 million children in the United States have
      enuresis. The pathophysiology of primary nocturnal enuresis involves the
      inability to awaken from sleep in response to a full bladder, coupled with
      excessive nighttime urine production or a decreased functional capacity of the
      bladder. Initial evaluation should include a history, physical examination, and
      urinalysis. Several conditions, such as constipation, obstructive sleep apnea,
      diabetes mellitus, diabetes insipidus, chronic kidney disease, and psychiatric
      disorders, are associated with enuresis. If identified, these conditions should
      be evaluated and treated. Treatment of primary monosymptomatic enuresis (i.e.,
      the only symptom is nocturnal bed-wetting in a child who has never been dry)
      begins with counseling the child and parents on effective behavioral
      modifications. First-line treatments for enuresis include bed alarm therapy and
      desmopressin. The choice of therapy is based on the child's age and nighttime
      voiding patterns, and the desires of the child and family. Referral to a
      pediatric urologist is indicated for children with primary enuresis refractory to
      standard and combination therapies, and for children with some secondary causes
      of enuresis, including urinary tract malformations, recurrent urinary tract
      infections, or neurologic disorders. 

PMID- 25369645
TI  - Screening for glaucoma.

PMID- 25369646
TI  - Chronic ulceration on the lower extremity. Localized cutaneous leishmaniasis.

PMID- 25369647
TI  - FPIN's Clinical Inquiries. Screening for autism spectrum disorders.

PMID- 25369652
TI  - Information from Your Family Doctor. Bed-wetting: Tips to Help Your Child.

PMID- 25369653
TI  - [Occurrence and characterization of monophasic Salmonella enterica subsp.
      enterica with antigenic formula 1,4, [5], 12: i:-isolated in Poland in 2007
      2012].
AB  - INTRODUCTION: Salmonella is significant etiological agent of bacterial intestinal
      infections in Poland and other European Union countries. Since the 90's
      increasing incidence of monophasic Salmonella antigenic formula 1,4,[5],12:i:-has
      been observed, which are divided into two lineages: Spanish and European. More
      common European lineage are characterized by antimicrobial resistance ASSuT and
      DT193 phagetype. In many European countries, these organisms have become one of
      the most commonly isolated serovars. The aim of this study was to analyze strains
      of Salmonella enterica subsp. enterica strains with antigenic formula 1,4,[5],12:
      i:-, isolated in Poland in 2007-2012 years. MATERIAL AND METHODS: The material
      for the study was 146 Salmonella strains initially identified as Salmonella
      antigenic formula 1,4,[5],12:i,-, isolated in 2007-2012 from clinical, food and
      animal samples. All strains has been reidentified according to the methodology
      routinely used in the laboratory. Serovar has been identified using classical
      method--slide agglutination for somatic and flagellar antigens and using
      Check&Trace Salmonella microarray. The fljB gene,fliB-fliA intergenic region,
      selected Salmonella Pathogenicity Islands' (SPIs) genes and spvC has been
      detected using PCR. For all strains PFGE typing with HindIII enzyme has been
      performed and phagetyping also. Moreover antimicrobial resistance has been
      evaluated by establishing of MIC according EUCAST recommendation. RESULTS: 110
      (75%) strains were S. enterica 1,4,[5],12:i,-. In this group for 17 strains in
      Check&Trace Salmonella microarray result of identification "Salmonella
      Typhimurium" have been obtained. All 110 strains have 1000 bp size DNA fragment
      with IS200 sequence, characteristic for S. Typhimurium. Only in case of 4 strains
      fljB gene has been detected. All strains harbor avrA, ssaQ, mgtC and siiD genes.
      For 6 strains spvC gene has been not detected. 92 strains (83.6%) have been typed
      as DT193, but in case of 40 strains additional reaction with phage no 18 has been
      observed. For 104 (94.5%) strains resistance for at least one antimicrobial have
      been detected. Most frequent (44 strains - 40%) resistance pattern was ASSuT.
      Among all strains 11 pulsotypes, which group two or more strains have been
      recognized, which contain 37 strains. The rest of strains have unique REA-PFGE
      patterns. CONCLUSIONS: To this time epidemiological situation of S. enterisa
      1,4,[5],12:i:- isolated from human cases in Poland has been not recognized.
      Results of current studies show, that studied strains belong to european non
      spanish lineage of monophasic S. Typhimurium and problem of infection caused by
      those strains is unrecognized and probably increase.

PMID- 25369654
TI  - Effectiveness of experimental whole-cell pertussis vaccines in murine model.
AB  - INTRODUCTION: Since the 1990s pertussis re-emergence has been observed in many
      highly immunized countries. Genetic divergence between circulating B. pertussis
      isolates and vaccine strains has been suggested as one of the reasons responsible
      for the resurgence of pertussis. This divergence was observed in some studies to
      affect the effectiveness of pertussis vaccine when tested in murine model. In the
      study, using the murine intranasal challenge model we evaluated the effectiveness
      of four experimental wP vaccines, prepared with B. pertussis isolates belonging
      to different PFGE groups, in the elimination of the bacterial infection induced
      with mixture of the four B. pertussis isolates. METHODS: The experimental wP
      vaccines were prepared with clinical isolates belonging to PFGE groups V, IVgamma
      and C, used individually or together. The mixture of four isolates classified to
      PFGE groups V, IVgamma, III and C was used as intranasal mice challenge. The
      chosen strains represent PFGE groups characteristic for isolates currently
      circulating in Europe (PFGE groups IV and V), specific for Poland (PFGE group C)
      and vaccine strains of Polish wP vaccine (PFGE group III). Additionally, to study
      bacterial fitness, changes in the proportions of four isolates used as the
      challenge within the course of infection in mice lungs were monitored. RESULTS
      AND CONCLUSIONS: All experimental wP vaccines were found to be equally effective
      in eliminating B. pertussis from mice lungs. Their effectiveness was independent
      on PFGE group of vaccine strain. The results on bacterial fitness during mixed
      infections induced in the non-immunized mice found the isolate of PFGE group
      IVgamma dominating among the other isolates used in the mixture belonging to PFGE
      group III, V, and C. This data might suggest that the isolates belonging to PFGE
      group IV, so commonly seen in Europe, might be more fitted to explore in
      conditions of waning immunity.

PMID- 25369655
TI  - [Development of molecular PCR-RFLP test for identification of the epidemic strain
      of Y. enterocolitica bioserotype 1B/O8 circulating in Poland since 2004].
AB  - INTRODUCTION: Highly pathogenic Y. enterocolitica bioserotype 1B/O8 is considered
      to be an important etiological agent of yersiniosis in Poland. Infections caused
      by Y. enterocolitica 1B/O8 became an important public health problem in Poland,
      especially because of their high potential of virulence and the unknown source of
      the bacteria. Y. enterocolitica 1B/O8 isolates recovered in Poland are
      genetically highly related and constitute single epidemic sensu stricto strain.
      The aim of the present study was to develop a time- and money-effective molecular
      assay for rapid identification of pathogenic Y. enterocolitica 1B/O8 isolates
      belonging to the epidemic strain. METHODS: In the first stage we performed a
      multiplex-PCR for four genetic markers: ail, ystA, irp1 and 16S rDNA sequence. In
      the next stage we designed a duplex-PCR-RFLP assay with BtsI endonuclease to
      detect/identify specific variant of an ysrR gene that is characteristic for
      epidemic strain of Y. enterocolitica 1B/O8 strain. The assay was tested against a
      panel of a consisted of a variety Yersinia enterocolitica and Y.
      pseudotuberculosis strains. RESULTS: All the tested Y. enterocolitica 1B/O8
      strains were positive for all the genetic markers in multiplex-PCR assay what
      distinguished them from other tested Yersinia strains. In duplex-PCR-RFLP test
      all tested isolates of the epidemic strain were negative for ysrR digestion with
      BtsI endonuclease, while all tested reference strains of Y. enterocolitica 1B/O8
      were positive. CONCLUSIONS: The assay developed in this study was two-stage/two
      step molecular test efficiently distinguishing wild-type and the epidemic Y.
      enterocolitica 1B/O8 strain. Such test can be a useful screening tool for
      clinical, veterinary and food diagnostics, as well as for the purposes of
      epidemiological investigation.

PMID- 25369656
TI  - [Resistance to ciprofloxacin of Neisseria gonorrhoeae strains isolated in Poland
      in 2012-2013].
AB  - INTRODUCTION: Ciprofloxacin is commonly used in Poland specially for the
      treatment of urinary tract infections including urethritis. Patients are often
      treated without pathogen identification and antimicrobial resistance tests.
      Neisseria gonorrhoeae infection is one of the most common causes of urethritis in
      Poland. The resistance of bacteria to a wide range of antibiotics including
      ciprofloxacine makes the therapy of gonorrhoea more difficult. The mechanism of
      ciprofloxacine action depends on inactivation of bacterial topoisomerase II
      (gyrase) and topoisomerase IV. A resistance to ciprofloxacine occurring in
      Neisseria gonorrhoeae is mainly due to mutations in bacterial gyrA (encoding
      topoisomerase II) and/or parC (encoding topoisomerase IV ) genes. High level
      resistance is an effect of combination of three or four mutations. Another, less
      important mechanism of ciprofloxacin resistance, that can coexist with mutations
      in gyrA and parC genes related to the overproduction of membrane pumps proteins.
      MATERIAL AND METHODS: 65 Neisseria gonorrhoeae strains isolated from patients of
      Department of Dermatology and Wenereology in Warsaw in the second half of 2012
      and first of 2013 was investigated. The strains were cultured on chocolate agar
      plates in a 5% CO2 atmosphere at 37 degrees C and identified by colony
      morphology, Gram stain and oxidase reaction, followed by carbohydrate utilization
      test. Ciprofloxacin susceptibility was determined by E-Tests (bioMerieux).
      Bacteria were incubated at 35 degrees C in 5% CO2 for 24 h on chocolate agar
      plates. Tests were performed according to producers recommendations. The results
      (sensitive or resistant) were interpreted according to EUCAST recommendations.
      RESULTS: The MIC (Minimal inhibitory concentration) of Ciprofloxacin in
      investigated strains ranged from 0,002 to > 32 mg/L, MIC50 = 8 mg/L, MIC90 = > 32
      mg/L. It was shown that only 38.5% of the strains were sensitive to ciprofloxacin
      according to EUCAST criteria from 2013 year. CONCLUSIONS: Due to the high
      percentage of ciprofloxacin resistant Neisseria gonorrhoeae strains (more than
      61%) the antibiotic should not be used for the treatment of gonorrhoea in Poland.

PMID- 25369657
TI  - [Seroprevalence of Mycoplasma pneumoniae in Poland in 2008-2013].
AB  - INTRODUCTION: Mycoplasma pneumoniae is a common causative agent of
      tracheobronchitis and atypical pneumonia, mainly in children and adolescents. The
      infections are often seen as epidemics occurring in autumn-winter seasons at
      intervals of 4-7 years. Epidemiological studies showed that M. pneumoniae is
      responsible for 30% to 40% of all cases of bacterial respiratory infections in
      Poland. The aim of the study was estimate the seroprevalence of M. pneumoniae in
      Poland in 2008-2013 in comparing to results obtained in other European countries.
      MATERIAL AND METHODS: The results of diagnostic serological tests (ELISA) in
      particular immunoglobulin classes for infection with M. pneumoniae performed in
      16.825 persons were retrospectively analyzed. The patients were mostly children
      at the preschool and school age with clinical symptoms of respiratory tract
      infection. The data were obtained from Bacteriology Department of National
      Institute of Public Health-National Institute of Hygiene in Warsaw and from 13
      Sanitary and Epidemiological Stations through the country which send quarterly or
      monthly reports. RESULTS: The serological results showed that in autumn-winter
      seasons of 2011-2012 the "early antibodies" (IgA and/or IgM) for M. pneumoniae
      were twice more often diagnosed in sera of patients with respiratory tract
      infection than in analogous seasons of 2008-2010. The antibodies were detected in
      34% and 42% of patients, respectively in third quarter of 2011 and 2012.
      CONCLUSIONS: Epidemic increase of M. pneumoniae infections in Poland in autumn
      winter seasons of 2011-2012 was mainly observed due to diagnosis of the IgA
      and/or IgM antibodies in serological tests.

PMID- 25369658
TI  - [The prevalence of active infection with viruses from the family Herpesviridae
      among members of families with children].
AB  - INTRODUCTION: Cytomegalovirus infection (CMV) is one of the most common viral
      infections during pregnancy and one of the most common causes of birth defects in
      newborns. CMV infection occurs mostly through close contact with small children
      who can secrete the virus in saliva and urine. Children, especially in preschool
      and early school can also be a source of infection with other herpesviruses. The
      aim of the study was to determine the prevalence of active infections caused by
      viruses from the family Herpesviridae (CMV, EBV, VZV) among members of families
      with children. MATERIAL AND METHODS: The study included 24 families raising
      children aged from 2 to 18 years. From all members of the families (46 adults and
      39 children) saliva samples were collected from which DNA was extracted. The
      isolated DNA samples were tested for the presence of CMV, EBV, VZV genetic
      material by nested PCR. In addition, each family carried out a survey. RESULTS
      AND CONCLUSIONS: The presence of CMV DNA in saliva samples were detected in
      members of 7 families and the presence of EBV DNA were detected in members of 11
      families. Total DNA of CMV was detected in 8/85 samples of saliva (9.41%), of
      which 1/46 adults (2.17%) and 7/39 children (17.95%) and EBV DNA was detected in
      18/85 tested saliva samples (21,18%) - 13/46 samples from adults (28,26%) and
      5/39 samples from children (12,82%). VZV DNA was not detected in any of the
      tested saliva samples. The obtained results indicate that the active,
      asymptomatic infections with lymphotropic herpesviruses are common and affect
      more than 10% (CMV) and 20% (EBV) subjects.

PMID- 25369659
TI  - [Inactivation of Candida species using cold atmospheric plasma on the way to a
      new method of eradication of superficial fungal infections].
AB  - INTRODUCTION: In recent years, nosocomial fungal infections are becoming an
      increasingly serious problem. More and more complications are observed in
      patients with high-risk groups resulting from the colonization of the skin and
      mucous membranes by Candida species. Thus, rapid and effective treatment of
      superficial fungal infections caused by Candida is a very important task for
      modern medicine. Unfortunately, with a clear increase in the number of fungal
      infections, the resistance to currently used antifungal drugs also increases
      seriously limited the effectiveness of treatment. An intensive search for new
      therapeutic solutions is therefore necessary. One of the promising solutions is
      the use of cold atmospheric plasma. The aim of this paper is to investigate the
      influence of this type of plasma on survival of Candida albicans. METHODS: As a
      source of cold atmospheric plasma, a linear microdischarge jet, called plasma
      razor, was used. Plasma was generated at 13.56 MHz, using He as a reactive gas.
      The gas flow rate and the discharge power were 1.9 L/min and 17 W, respectively.
      A schematic view of the experimental system is shown in Fig. 1. The reference
      strain of Candida albicans ATCC 10231 was used as a model material for
      investigations. The culture was prepared by spreading uniformly 100 MUL phosphate
      buffered saline solution containing 5 x10(7) cells/mL on the surface of a Petri
      dish. Such a culture was exposed to the plasma at various times. The size of the
      zone of inhibition of fungal growth was estimated by densitometric method (Fig.
      3). For more complete information about the plasma the optical emission spectra
      were measured. RESULTS: It was found that with increasing time of plasma
      treatment, the zone of inhibition clearly increases (Fig. 2). In Fig. 4, the
      experimental results of the size of the inhibition zone versus the treatment time
      are shown. These results were successfully fitted (p = 0.0058, r2 = 0.944) by a
      theoretical curve (Fig. 4), plotted according to Eq. (5), which was derived on
      the basis of a simple model of the spread of a killing agent from the plasma
      center. The study of the optical emission spectra confirmed a large variety of
      possible killing agents generated in the cold atmospheric plasma, such as UV,
      radicals, ions and energetic electrons. Further research will be focused on the
      determination of the main agent responsible for the process of the cell killing,
      and to determine the mechanism of this process. CONCLUSIONS: Cold atmospheric
      plasma generated by the plasma razor turns out to be a very effective tool for
      the killing of pathogenic fungi. Although the presented studies are only the
      initial stage of work on the effects of cold atmospheric microplasma on fungal
      cells, they provide hope for the possibility of using this technique as a method
      of eradication of superficial fungal infections.

PMID- 25369660
TI  - [The antibacterial activity of cinnamon oil on the selected gram-positive and
      gram-negative bacteria].
AB  - INTRODUCTION: The aim of our study was to determine the antibacterial activity of
      cinnamon bark oil against Gram-positive and Gram-negative isolates belonging to
      Staphylococcus, Enterococcus, Enterobacter and Acinetobacter genera come from
      different clinical specimens. METHODS: The microdilution method was used to
      determine the minimum inhibitory concentration--MIC for cinnamon bark oil.
      Susceptibility testing to antibiotics was carried out using disc-diffusion
      method. RESULTS: Our investigations showed that the tested cinnamon bark oil was
      inhibiting activity against all isolates. The MIC for Gram-positive bacteria were
      between 01.25 and 1.5 MUl/ml and for Gram-negative between 1.0 and 1.75 MUl/ml.
      The tested bacteria come from Staphylococcus, Enterococcus, Enterobacter and
      Acinetobacter genera were susceptible to essential oil obtained from Cinnamomum
      zeylanicum Ness in low concentrations, despite the fact that the bacteria
      characterized the high resistance to recommended antibiotics. No correlation was
      found between the antibiotic resistance of the bacterial strains and their
      sensitivity to essential oil. CONCLUSIONS: The cinnamon bark oil due to the
      strong activity can be used as alternative antibacterial agents in cosmetics,
      toiletries and disinfectants applied in hospital environment.

PMID- 25369661
TI  - [Blisters after sun exposure].

PMID- 25369662
TI  - ["Every single assault prevented is worth the effort"].

PMID- 25369663
TI  - [Innovations enhance your practice for young physicians].

PMID- 25369664
TI  - [Office hours on Saturday without plausibility check].

PMID- 25369665
TI  - [Work incapacity certification may not have any loopholes].

PMID- 25369666
TI  - [Prioritization does not place in an ethical vacuum].

PMID- 25369667
TI  - ["Will you give me your stool?"].

PMID- 25369668
TI  - [Stool transplantation: also an option for irritable bowel syndrome?].

PMID- 25369669
TI  - [Unfavorable prognosis, imminent dementia].

PMID- 25369670
TI  - [Should type 2 diabetics lose weight or better not?].

PMID- 25369671
TI  - [What kind of thrombosis prevention for travel?].

PMID- 25369672
TI  - [Loosing weight with soccer].

PMID- 25369673
TI  - [That was too much for the eye].

PMID- 25369674
TI  - [Blood pressure self and long-term monitoring for therapy control are equally
      effective].

PMID- 25369675
TI  - [Fit with 50 - long life].

PMID- 25369676
TI  - [Juvenile multiple sclerosis is increasing].

PMID- 25369677
TI  - [Tests for occult blood in stool fail in routine practice].

PMID- 25369678
TI  - [Be prepared for summer emergencies].

PMID- 25369679
TI  - [Management of bleeding scalp lacerations].

PMID- 25369680
TI  - [Hair apposition technique for scalp lacerations].

PMID- 25369681
TI  - [Management of plantar puncture wound].

PMID- 25369682
TI  - [Emergency management in allergic reactions to insect stings].

PMID- 25369683
TI  - [Escape from the wrong gender].

PMID- 25369684
TI  - [Male infertility--pathogenic factors].

PMID- 25369685
TI  - [Support for speaking with the patient in general practice].

PMID- 25369686
TI  - [Different causes of dysphonia].

PMID- 25369687
TI  - [Cardiac diagnostic in hypertension].

PMID- 25369688
TI  - [What is essential in diagnosis?].

PMID- 25369689
TI  - ["Neuropathic backaches require different management"].

PMID- 25369690
TI  - [Pregabalin improves pain and important comorbidities].

PMID- 25369691
TI  - [Approaches to improving therapeutic success].

PMID- 25369692
TI  - [Medical certification: at the crossroads of medicine, patient demands and the
      right of society].

PMID- 25369693
TI  - [Medical fitness and sick leave documentation: rules and uses].
AB  - Primary care physicians frequently have to respond to patients' requirements for
      medical documentation. Those include certification about fitness and ability to
      engage in specific activities and about inability to work due to ongoing health
      problems, which engages physicians' legal and profesionnal responsability. To
      clarify the rules and modalities of this activity, we present here the legal
      framework and the good practices. Regarding the sick leave certification, there
      are well-defined profesionnal and legal guidelines, which is not the case for
      certification about fitness.

PMID- 25369694
TI  - [Driving ability: how not to lose control?].
AB  - Any primary care doctor should be able to decide on the fitness to drive of a
      given patient. The issue of an older driver, patients addicted to alcohol or
      drugs, under current psychotropic drug treatment, or diabetic, is discussed in
      the light of legal provisions and current recommendations. This article also
      discusses aspects associated with neurological, cardiac and orthopedic issues.

PMID- 25369695
TI  - [Medical consult before taking a plane: assessment and advice by the primary care
      physician].
AB  - Many of our patients travel by air. During the flight, they are exposed to
      specific physical conditions: decrease of the PaO2, increase of body gas volume
      and decrease in humidity. Depending on their illness, their tolerance to these
      conditions may vary. The primary care physician's role is to adequately counsel
      patients in order to ensure their security during and after the flight, as well
      as to prescribe additional therapies, when needed. Patients with a hypoxemic
      medical condition or patients that were recently operated deserve particular
      attention. Complications of common ear, nose and throat diseases should not be
      underestimated. Preventive recommendations for thromboembolic disease need to be
      addressed, while drug prophylaxis is not systematically recommended any more for
      patients with major thromboembolic risk factors.

PMID- 25369696
TI  - [The sports preparticipation medical screening].
AB  - Globally, populations are more and more physically active in western countries,
      also participating in competitions, even if not professionally. The main goals of
      the sports preparticipation screening is to detect conditions that may predispose
      to injuries, may cause sudden death, or trigger worsening in preexisting
      conditions. In Switzerland, primary care physicians are regularly confronted to
      it. The requests mainly come from people practicing sports in bordering
      countries, where the examination is mandatory, or from people concerned with
      their health. This article reviews the essential points of this examination,
      mainly consisting in history taking and physical examination. On a cardiovascular
      point of view, it details the main differences between the European and the
      American recommendations regarding athletes between 12 to 35 years old and those
      older.

PMID- 25369697
TI  - [Medical certification for high altitude travel and scuba diving].
AB  - People are more and more looking for adventures and discovery of unusual
      locations. Journeys to high altitude and scuba diving are part of these
      activities and their access has become easier for a lot of people not necessarily
      experienced with their dangers. The general practitioner will have to be able to
      deliver some advices and recommendations to his patients about the risks related
      to these activities and their ability to practice them. He will also have to
      deliver some certificates of medical fitness to dive. This paper proposes a brief
      review of the most important medical aspects to know about high altitude and
      scuba diving.

PMID- 25369698
TI  - [The 2014 Swiss adults immunization schedule: guidelines for medical
      practitionners].
AB  - The 2014 recommendations regarding adult immunization in Switzerland include the
      use of the 13-valent anti-pneumococcal vaccine instead of the 23-valent in
      patients at high risk of invasive infection and of the influenza vaccine during
      the entire pregnancy. This article reviews these recommendations and discusses
      situations requiring specific immunizations schemes.

PMID- 25369699
TI  - [Healthcare professionals dealing with burnout: risk factors and preventive
      measures].
AB  - Although sometimes called "disease of the century", the burnout doesn't inspire a
      lot of prevention, and is still a taboo, for most of people suffering of this
      malaise. The healthcare professionals represent a risky population and most of
      them are not aware of it. Unfortunately existing preventive measures are still
      badly known. Nevertheless it seems necessary to try to prevent if not slow down
      the development of this disease before it leads to excessive damages for our
      already suffering society... Talking about this pathology is quite easy but it is
      much more difficult than generally thought to admit being personally touched and
      to look for appropriate help.

PMID- 25369700
TI  - [Adolescents on antipsychotics: What is the situation with ability?].

PMID- 25369701
TI  - [Response].

PMID- 25369702
TI  - [The urgency to kill: two concrete cases of contemporary ethics].

PMID- 25369703
TI  - [The pain of the world].

PMID- 25369704
TI  - [France will soon be able to end its mandatory vaccinations].

PMID- 25369705
TI  - [Rotavirus vaccination and invagination: a significant risk?].

PMID- 25369706
TI  - [When suffering is written down].

PMID- 25369707
TI  - [Public case: who falsified the numbers?].

PMID- 25369708
TI  - [Nurses: the shortage worsens].

PMID- 25369709
TI  - [Ebola: the moral bankruptcy and the irrational].

PMID- 25369710
TI  - [Carcinogenic risk of polycyclic aromatic hydrocarbons: classification and
      interpretation of the monitoring].
AB  - The polycyclic aromatic hydrocarbons (PAHs) are widespread contaminants
      characterized by various chemical, physical and toxic properties. The
      characterization of occupational and environmental exposures and the use of
      suitable measurements protocols are very significant because their presence in
      mixtures and environmental persistency. In the past few years, the knowledge
      concerning carcinogenicity of PAHs have been reviewed, the mechanisms involved
      are the interaction of PAH's metabolites with DNA and oxidative damages. The main
      requirement for research concerns lack of knowledge on reference values and
      occupational exposure's assessment in particular PAHs sampling methods that can
      lead to combined measurements of vapor and aerosol mixtures. Aims of this study
      are to describe a possible occupational sources of PAHs providing also an update
      of mechanism involved in their carcinogenicity and risk calculation as is done in
      the TEF approach. The classifications provided by International Agencies and
      Institutions and the limit values adopted have been reviewed and taken into
      account.

PMID- 25369711
TI  - [Infections of the hand in a working context].
AB  - Hand infections still are a major issue, despite a remarkable decrease in their
      incidence has been reported due to the increasing in the use of protections in
      the work environment and a proper professional education. On one hand, medical
      therapy offered new, revolutionary and powerful devices, on the other one,
      surgical therapy still is an efficient and unique treatment modality. Therefore,
      modern therapeutic strategies are based on a combined approach of medicine and
      surgery. From an exhaustive analysis of the present literature and based on
      Italian and international long-tradition hospitals' experience, Authors present
      an extensive discussion about occupational hand infections. It includes a
      presentation of aethiological agents, anatomo-pathological and medical cases in
      relation to most suitable medical and surgical therapeutic devices.

PMID- 25369712
TI  - [Pseudomonas infection: biological risk by occupational exposure and results of
      an environmental monitoring].
AB  - The biological risk of Pseudomonas aeruginosa for activities involving exposure
      to contaminated water, such as, for example, routine maintenance of swimming
      pools, is related to the availability of effective prophylactic and therapeutic
      measures. The authors present the data of the microbiological analyzes made on
      2349 samples taken from pools in Rome and province. The contamination by
      Pseudomonas was found in 191 samples with 13 samples that had a level > 100
      cfu/100 ml and 5 samples with level > 200 cfu/100 ml. Useful considerations
      derived from the analysis of the literature about the profile and prophylactic
      treatment of infection by Pseudomonas, necessarily to be taken into consideration
      for an adequate risk assessment.

PMID- 25369713
TI  - Exposure to formaldehyde in health care: an evaluation of the white blood count
      differential.
AB  - The aim of our study is to estimate if the occupational exposure to formaldehyde
      can cause alterations of leukocytes plasma values in health care workers employed
      in a big hospital compared to a control group. We studied employees in operating
      rooms and laboratories of Pathological Anatomy, Molecular Biology, Molecular
      Neurobiology, Parasitology and Experimental Oncology (exposed to formaldehyde)
      and employees of the Department of Internal Medicine (not exposed). The sample
      studied was composed of 86 workers exposed to formaldehyde and 86 workers not
      exposed. All subjects underwent a clinical-anamnaestic examination and for all
      subjects were measured the following values: total white blood cells,
      lymphocytes, monocytes and granulocytes (eosinophils, basophils, neutrophils).
      Statistical analysis of data was based on calculation of the mean, standard
      deviation and the distribution into classes according to the nature of each
      variable. Differences were considered significant when p was < 0.05. The mean and
      the distribution of values of the white blood cells, lymphocytes, monocytes and
      eosinophils were significantly higher in male subjects exposed to formaldehyde
      compared to not-exposed. Not significant differences were found in female
      subjects exposed compared to not exposed. The results underline the importance of
      a careful risk assessment of workers exposed to formaldehyde and the use of
      appropriate preventive measures. The health care trained and informed about the
      risks he is exposed to should observe good standards of behavior and, where it is
      not possible to use alternative materials, the indoor concentrations of
      formaldehyde should never exceed occupational limit values.

PMID- 25369714
TI  - [Job satisfaction in an Italian university: difference between academic and
      technical-administrative staff].
AB  - OBJECTIVE: The changes in the academic world led to an increase in job demands
      and a decrease in the available job resources. In recent years, the positive
      image of work in academia has gradually blurred. The present study, within the
      theoretical framework of the job demands-resources model, aimed to analyse the
      relationship between some job demands (workload, work-family conflict and
      emotional dissonance) and some job resources (autonomy, supervisors' support and
      co-workers' support) and job satisfaction in a medium-sized Italian University,
      by observing the differences between the academic staff (professors and
      researchers) and the technical-administrative staff METHODS: The research was
      conducted by administering a self-report questionnaire which allowed to detect
      job satisfaction and the mentioned variables. Respondents were 477 (177 from
      academic staff and 300 from technical-administrative staff). RESULTS: The
      analysis of variance (independent samples t-test) showed significant differences
      in variables of interest between academic staff and technical-administrative
      staff. Multiple regression pointed out that job autonomy is the main determinant
      of job satisfaction in the academic staff sample, whereas supervisor support is
      the main determinant of job satisfaction in the technical-administrative staff
      sample. CONCLUSIONS: This research represents one of the first Italian studies on
      these topics in the academic context and highlights the importance of further in
      depth examinations of specific job dynamics for both teaching and technical
      administrative staff. Among practical implications, the importance of keeping
      high levels of job autonomy for academic staff and of fostering an effective
      leadership development for technical-administrative staff emerged.

PMID- 25369715
TI  - [Safety of use assessment in a radio-frequency medical device].
AB  - The authors assessed the operating safety physical parameters of a bipolar
      radiofrequency device for aesthetic purposes. According to both Italian and EU
      guidelines, the authors considered: magnetic field environmental emission levels,
      electricity induced in the opertator's limbs, operator's exposure and
      radiofrequency specific absorbance rate (SAR) in treated tissues. Measurements
      were carried out with isotropic sensors and an inductive current indicator.
      Results pointed out excellent safety levels regarding environment, operators and
      patients as well, although such radiofrequency equipment cannot be used on
      patients with pacemakers, neurostimulators and other vital function controlling
      devices.

PMID- 25369716
TI  - [Discriminating capacity of the MASI-R questionnaire in the perception of work
      stress].
AB  - INTRODUCTION: Workplace mobbing represents a severe type of occupational stress.
      The aim of this study is to evaluate the discriminant validity of the Maugeri
      Stress Index-Revised questionnaire (MASI-R) for the perceived work stress
      assessment. METHODS: A total of 105 patients were enrolled at the Occupational
      Medicine Uinit of our Institute for mobbing-related issues; they were compared to
      a control group matched for age, sex and professional category. Work stress
      perception was assessed in both samples using the self-report questionnaire MASI
      R, which is the Maugeri Stress Index short form. RESULTS: Workers who perceived
      exposure to mobbing scored significantly lower compared to the control group in
      the four MASI-R scales (p < 0.001) and in the two visual analogue scales
      measuring job satisfaction (p < 0.001) and life satisfaction (p < 0.001). Further
      analyses have identified the items which significant discriminate between the two
      groups of workers. CONCLUSIONS: These findings show a good discriminant validity
      of the MASI-R questionnaire: workers who perceived exposure to workplace mobbing
      reveal higher work stress levels compared to the control group in all aspects
      measured.

PMID- 25369717
TI  - [Prevalence of workplace bullying in a population of nurses at three Italian
      hospitals].
AB  - Negative behaviors could be considered as a risk index of workplace bullying;
      researching on these events is useful for the planning of preventive
      interventions. The aim of this study was to investigate the prevalence of
      negative actions in a population of nurses and their possible association with
      issues related to mental health. We administered a proper questionnaire, based
      both on the NAQ-R and on the GHQ12, to 206 subjects, who worked in three
      hospitals, located in the center and south of Italy. Our results confirmed that
      the nursing profession presents a clear bullying risk in the workplace, without
      any notable differences regarding gender or demographics. The prevalence of
      negative actions was noteworthy, mainly with regard to the job position and the
      task. Our study also showed that workplace bullying may interfere with the
      overall health of nurses, particularly connected to psycho-emotional issues.

PMID- 25369718
TI  - Monitoring iliopsoas muscle contraction in idiopathic lumbar scoliosis patients.
AB  - BACKGROUND: Curve evolution in idiopathic scoliosis frequently occurs in lumbar
      and thoracic-lumbar spine. The spinal and iliopsoas muscles play a major role in
      maintaining the static and dynamic stability of the spine. OBJECTIVE: To monitor
      by video recording, the degree to which asymmetric isometric contractions of the
      iliopsoas muscle improve the lumbar curve. DESIGN: 10 subjects (9 female, 1
      male), mean age of 14.1 years (11-18), who were undergoing rehabilitation for
      idiopathic scoliosis. 8 subjects wore a brace, 6 had a single lumbar curve, 4 had
      a thoracic curve; 9 curves were convex to the left and 1 convex to the right. The
      mean Cobb angle was 20.1 degrees +/-8.2523) with a mean degree of rotation of 1.2
      (+/-0.4216). METHOD: The scoliotic curves were monitored on video whilst the
      patients performed muscle contraction exercises. Adhesive markers were applied to
      the skin to be used as reference points of the curve on video. Subjects performed
      the exercises in a sitting position, facing away from the video camera, with
      their knees bent at an angle of 90 degrees. The complete exercise procedure was
      as follows: initial lengthening of the spine and postural control, concentric
      activation of the iliopsoas, isometric activation for about 3 seconds, then final
      release. Differences in curvature angle detected on the video recording were
      analysed and processed using the computer software Dartfish Pro Suite
      5.0_Dartfish LTD_Switzerland. RESULTS: The mean angle of correction through
      exercise was 6.9 degrees (+/-3.6) during concentric activation and 4.9 degrees
      (+/-3.5) during isometric activation of the iliopsoas. CONCLUSIONS: Data show the
      corrective effect that iliopsoas muscle contraction produces on the scoliotic
      curve.

PMID- 25369719
TI  - What social workers need to know about the retirement income crisis.

PMID- 25369720
TI  - Using spiritually modified cognitive-behavioral therapy in substance dependence
      treatment: therapists' and clients' perceptions of the presumed benefits and
      limitations.
AB  - Cognitive-behavioral therapy (CBT) that has been modified to incorporate clients'
      spiritual beliefs and practices has been used to treat a variety of problems.
      This study examines the utility of this modality with the treatment of alcohol
      dependence and other forms of substance abuse. Toward this end, six focus groups
      (three therapist groups and three client groups) were conducted to identify the
      presumed benefits and limitations of using spiritually modified CBT in substance
      dependence treatment. In terms of benefits, spiritually modified CBT was
      perceived to enhance outcomes through operationalizing horizontal and vertical
      sources of social support, divine coping resources, and spiritual motivation.
      Potential challenges include the risk of therapists inadvertently imposing their
      own beliefs during the modification process and the possibility of offending
      clients when conflicts in belief systems emerge, particularly in group setting.
      The article concludes by providing suggestions for incorporating spiritually
      modified CBT into treatment and develops a number of illustrative examples of
      spiritually modified CBT self-statements.

PMID- 25369721
TI  - Cultural differences in perinatal experiences for women with low socioeconomic
      status.
AB  - In this study, similarities and differences in perinatal experiences between
      women with low socioeconomic status (SES) by race, ethnicity, and nativity were
      explored. The objective was to better understand the sociocultural and
      environmental contexts ofperinatal experiences and potential implications for
      screening and assessment among women with low SES. A purposive stratified sample
      of 32 women who were likely to be screened for perinatal depression participated
      in four focus groups organized by African American, white, Hmong, or Latina race
      or ethnicity. A descriptive study design was used to collect and evaluate focus
      group data using qualitative content analysis. Women understood their perinatal
      experiences through the stressors in their environment. The stressors of
      insufficient socioeconomic resources and interpersonal support were relatively
      consistent across the focus groups. However, women's understanding of these
      stressors and their meaning differed between groups. Racially and ethnically
      diverse women with low SES experienced a complex interaction of sociocultural and
      environmental factors in the perinatal period. The findings highlight the need
      for health and social work practitioners to conduct depression screenings in
      conjunction with a com- prehensive psychosocial assessment, informed by cultural
      competence.

PMID- 25369722
TI  - Physical and mental health correlates of adverse childhood experiences among low
      income women.
AB  - The present study used secondary data gathered from a statewide random sample of
      1,073 adult women enrolled in Utah's single-parent cash assistance program and
      logistic regression to examine associations between self-reported physical,
      emotional, and sexual abuse during childhood and later life physical and mental
      health indicators. Results demonstrated significant associations between low
      income women's self-reports of physical, emotional, or sexual abuse in childhood,
      and current and lifetime anxiety disorder, domestic violence, current
      posttraumatic stress disorder, bipolar disorder, physical health or mental health
      issues, and any mental health diagnosis. These results build on previous research
      to paint a fuller picture of the associations between childhood abuse and
      physical and mental health for low-income women in Utah. Consistent with research
      by the Centers for Disease Control and Prevention, findings suggest the
      applicability of conceptualizing childhood abuse as a public health issue. Social
      workers can play an integral role in promoting and implementing broader screening
      practices, connecting affected individuals with long-term interventions, and
      applying research findings to the design and provision of services within a
      public health model.

PMID- 25369723
TI  - Determinants of health concentration selection among University of Southern
      California MSW students.
AB  - By 2020, health care social workers are projected to make up 25 percent of the
      entire number of professional social workers in the United States. At the
      University of Southern California, the number of graduate students selecting the
      health social work concentration has increased exponentially over the last five
      years. Although there are no published findings to indicate that other schools of
      social work are experiencing a similar trend, the Bureau of Labor Statistics has
      reported that, nationally, the number of social workers employed in health care
      has increased and is projected to continue increasing over the next decade. The
      purpose of this study was to identify decision-making determinants of MSW
      students pursuing a specific vocational interest in health care settings. The
      study used a questionnaire to gather quantitative and qualitative data from a
      population of MSW students. The findings suggest that graduate students select
      the health concentration based on self-knowledge (abilities and interests) and
      vocational knowledge (job demands and labor market). This article concludes with
      a discussion of the implications of these findings for health social work
      curriculums, practice, research, policy, and the integral role social workers
      play in health care reform in the present and will play in the future.

PMID- 25369724
TI  - Sociocultural factors of teenage pregnancy in Latino communities: preparing
      social workers for culturally responsive practice.
AB  - Despite gains in reducing teenage pregnancy during the past 20 years, disparities
      in teenage pregnancy rates persist: The teenage pregnancy rate in Latino
      communities is now nearly double the average rate of teenage pregnancy in the
      United States. Considering the significant risks teenage pregnancy and parenting
      pose to both the teenager and the child, and that social workers are already
      often working in communities with populations at risk, this is not only a major
      public health issue, but one that the field of social work is well positioned to
      actively address. This article synthesizes pertinent literature on some of the
      social and cultural influences important for understanding this phenomenon.
      Implications for social work practice are discussed.

PMID- 25369725
TI  - Rethinking family caregiving: tailoring cognitive-behavioral therapies to the
      hospice experience.
AB  - Hospice family caregivers experience significantly higher rates of psychological
      distress than demographically similar noncaregivers. Interventions based on
      cognitive-behavioral therapy have been shown to reduce psychological distress in
      the general population by providing tools to modify thinking patterns that
      directly affect emotions and behavior. Such interventions might reasonably be
      incorporated into hospice social work; however, numerous contextual factors must
      be taken into account to ensure that any interventions are appropriate to the
      unique needs of clients. The purpose of the study discussed in this article was
      to contex- tualize one aspect of the cognitive-behavioral model based on
      firsthand accounts of hospice family caregivers. Following a modified grounded
      theory approach, researchers engaged in a secondary analysis of data from a
      larger study provided in a subsample of 90 audio-recorded conversations between
      hospice family caregivers and interventionists. Findings indicated that
      distressed caregivers engaged in five dominant thinking patterns: (1) "should"
      statements, (2) catastrophizing or minimizing, (3) personalizing, (4) absolute
      thinking, and (5) making assumptions. Implementing cognitive-behavioral therapies
      based on identified caregiver thinking patterns will allow hospice social workers
      to empower caregivers to cope more effectively with the numerous stressors they
      encounter while caring for a dying loved one.

PMID- 25369726
TI  - Considering the prominent complaint as a guide in medical therapy for overactive
      bladder syndrome in women over 45 years.
AB  - AIM: The aim of this study was to evaluate the response of women over 45 years
      with overactive bladder and detrusor overactivity to a 12-week course of
      oxybutynin or tolterodine treatment. MATERIAL AND METHODS: A total of 301
      eligible Iranian women were studied. In this double-blinded trial, data were
      analyzed from 3-day urinary diaries from before and after 12 weeks of treatment
      in which patients were randomly assigned to receive oxybutynin or tolterodine in
      recommended doses. Patients' convenience and the drugs' side-effects were
      assessed by a monthly clinical appointment. End-points were changed from baseline
      to week 12 in bladder-diary variables and all observed or reported adverse
      events. The effectiveness of each drug was studied using the paired t-test and
      improvement after treatment between the two groups was compared by independent t
      test. RESULTS: Mean improvements in the terms of urgency (P = 0.64) and urge
      incontinence (P = 0.75) showed an insignificantly larger score in patients who
      were treated by oxybutynin. Improvement in night-time urinary urgency and
      nocturia (41.2% and 54.3% vs 39.7% and 40.1% in oxybutynin vs tolterodine groups,
      respectively) were shown to be more improved by tolterodine in comparison to
      oxybutynin (P = 0.72 and 0.04 for night-time urinary urgency and nocturia,
      respectively). Discontinuation of treatment due to adverse events was not
      significantly different in the two groups. CONCLUSIONS: Oxybutynin and
      tolterodine showed similar efficacy on daytime symptoms of overactive bladder and
      similar side-effects in perimenopausal patients. For patients with the chief
      complaint of nocturnal frequency, prescription of tolterodine is preferably
      suggested.

PMID- 25369727
TI  - Metabolic profiling analysis of berberine, palmatine, jatrorrhizine, coptisine
      and epiberberine in zebrafish by ultra-high performance liquid chromatography
      coupled with LTQ Orbitrap mass spectrometer.
AB  - 1. Zebrafish has been used in metabolic study of drugs as a powerful tool in
      recent years. In this study, we make a feasible metabolism investigation of five
      protoberberine alkaloids (PBAs) applied in zebrafish model for the first time,
      including berberine (BBR), palmatine (PAL), jatrorrhizine (JAT), coptisine (COP)
      and epiberberine (EBBR). 2. After exposure for 24 hours, 19 metabolites were
      identified by LTQ Orbitrap mass spectrometer, including 9 phase I metabolites and
      10 phase II metabolites. Demethylation, hydroxylation, sulfation and
      glucuronidation were the major metabolic transformation of PBAs in zebrafish,
      which were similar to mammals. Compared with reported literatures, BBR and JAT
      showed high consistency between human and zebrafish in metabolic pathways. 3. To
      our knowledge, this is the first time to study in vivo metabolism of COP, which
      provides useful information to other researchers. 4. This study indicated that
      zebrafish model is feasible and reasonable to predict the metabolism of PBAs. It
      showed great potential for developing a novel and rapid method for predicting the
      metabolism of trace compounds of botanical drugs, with the advantages of lower
      cost, higher performance and easier set up. 

PMID- 25369729
TI  - Multiplexed and amplified electronic sensor for the detection of microRNAs from
      cancer cells.
AB  - The detection of microRNA expression profiles plays an important role in early
      diagnosis of different cancers. On the basis of the employment of redox labels
      with distinct potential positions and duplex specific nuclease (DSN)-assisted
      target recycling signal amplifications, we have developed a multiplexed and
      convenient electronic sensor for highly sensitive detection of microRNA (miRNA)
      141 and miRNA-21. The sensor is constructed by self-assembly of thiol-modified,
      redox species-labeled hairpin probes on the gold sensing electrode. The
      hybridizations between the target miRNAs and the surface-immobilized probes lead
      to the formation of RNA/DNA duplexes, and DSN subsequently cleaves the redox
      labeled hairpin probes of the RNA/DNA duplexes to recycle the target miRNAs and
      to generate significantly amplified current suppression at different potentials
      for multiplexed detection of miRNA-141 and miRNA-21 down to 4.2 and 3.0 fM,
      respectively. The sensor is also highly selective toward the target miRNAs and
      can be employed to monitor miRNAs from human prostate carcinoma (22Rv1) and
      breast cancer (MCF-7) cell lysates simultaneously. The sensor reported here thus
      holds great potential for the development of multiplexed, sensitive, selective,
      and simple sensing platforms for simultaneous detection of a variety of miRNA
      biomarkers for clinic applications with careful selection of the labels. 

PMID- 25369728
TI  - Surface charge, electroosmotic flow and DNA extension in chemically modified
      thermoplastic nanoslits and nanochannels.
AB  - Thermoplastics have become attractive alternatives to glass/quartz for
      microfluidics, but the realization of thermoplastic nanofluidic devices has been
      slow in spite of the rather simple fabrication techniques that can be used to
      produce these devices. This slow transition has in part been attributed to
      insufficient understanding of surface charge effects on the transport properties
      of single molecules through thermoplastic nanochannels. We report the surface
      modification of thermoplastic nanochannels and an assessment of the associated
      surface charge density, zeta potential and electroosmotic flow (EOF). Mixed-scale
      fluidic networks were fabricated in poly(methylmethacrylate), PMMA. Oxygen plasma
      was used to generate surface-confined carboxylic acids with devices assembled
      using low temperature fusion bonding. Amination of the carboxylated surfaces
      using ethylenediamine (EDA) was accomplished via EDC coupling. XPS and ATR-FTIR
      revealed the presence of carboxyl and amine groups on the appropriately prepared
      surfaces. A modified conductance equation for nanochannels was developed to
      determine their surface conductance and was found to be in good agreement with
      our experimental results. The measured surface charge density and zeta potential
      of these devices were lower than glass nanofluidic devices and dependent on the
      surface modification adopted, as well as the size of the channel. This property,
      coupled to an apparent increase in fluid viscosity due to nanoconfinement,
      contributed to the suppression of the EOF in PMMA nanofluidic devices by an order
      of magnitude compared to the micro-scale devices. Carboxylated PMMA nanochannels
      were efficient for the transport and elongation of lambda-DNA while these same
      DNA molecules were unable to translocate through aminated nanochannels. 

PMID- 25369731
TI  - Effect of surface Si redistribution on the alignment of Ge dots grown on pit
      patterned Si(001) substrates.
AB  - Thermally activated redistribution of Si surface atoms is found to be a crucial
      factor for the growth of aligned Ge dots on pit-patterned Si(001) substrates. A
      phenomenon of Si accumulation around the edge of pits significantly alters the
      substrate surface morphology. As the pit spacing is reduced to below 100 nm, a
      convex morphology developed between adjacent pits causes a chemical potential
      distribution that drives the Ge dots into the pits. In addition, the pits of an
      etching depth greater than 60 nm will evolve into truncated inverted pyramids
      with sharp base corners that provide deep potential wells for the confinement of
      Ge dots. Perfectly aligned Ge dots are obtained on pit-patterned Si substrates
      with this range of pit spacing and etching depth. We also find that the initial
      geometric shape of the pits does not affect the spatial arrangement of Ge dots. 

PMID- 25369730
TI  - Oxaliplatin-based versus irinotecan-based hyperthermic intraperitoneal
      chemotherapy (HIPEC) in patients with peritoneal metastasis from appendiceal and
      colorectal cancer: a retrospective analysis.
AB  - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) provide an effective treatment option for selected patients
      with colorectal peritoneal metastasis with encouraging survival results. Many
      different drug combinations and HIPEC regimens including bidirectional, i.e.
      synchronous intravenous and intraperitoneal, drug application have been used.
      However, there is still no standardization of the HIPEC regimen. METHODS: Between
      05/2007 and 04/2010 190 patients underwent CRS and HIPEC at the University
      Hospital Regensburg. Thirty-two patients with peritoneal metastasis arising from
      colorectal or appendiceal cancer underwent complete macroscopic cytoreduction (CC
      0/1) and bidirectional HIPEC and completed at least 3-year follow-up. Twenty
      patients received oxaliplatin-based (OX) and twelve patients received irinotecan
      based HIPEC (IRI). Group-specific perioperative morbidity and 3-year survival has
      been determined. RESULTS: The grade 3/4 morbidity rate according to CTCAE v4 was
      35.0% in the OX group vs. 33.3% in the IRI group (p = 1.000). There was no
      perioperative mortality in both groups. Median survival was 26.8 months (95% CI
      15.7-33.1 months) in the IRI group and has not yet been reached in the OX group
      during a median follow-up of 39.4 months. Three-year survival rates were 65.0% in
      the OX group vs. 41.7% in the IRI group (p = 0.295). CONCLUSIONS: The morbidity
      and toxicity rates of bidirectional irinotecan-based and oxaliplatin-based HIPEC
      are comparable. Nevertheless, in the absence of contraindications oxaliplatin
      based HIPEC might be preferred due to the positive trend regarding 3-year and
      median survival.

PMID- 25369732
TI  - The process of translating family nursing knowledge into clinical practice.
AB  - PURPOSE: To report on approaches that were used to assist with implementation of
      family systems nursing (FSN) at a university hospital level in Northern Europe.
      DESIGN AND METHODS: A quasi-experimental research design was used for the first
      phase of the study. For the second phase, a cross-sectional research design was
      used. Data were collected in the first phase of the study from 457 nurses in all
      except one of the divisions of the hospital regarding their attitudes towards
      involving families into their care before and after having participated in the
      education and training intervention (ETI) program in FSN. Furthermore, in the
      second phase, data were collected from 812 nurses, after FSN had been implemented
      in all divisions at Landspitali University Hospital, regarding the nurses'
      knowledge of FSN and their evaluation of the quality of the ETI program (i.e.,
      theoretical lectures on FSN as well as the benefit of the skill lab training
      regarding applying FSN into their clinical practices). Graham and colleagues'
      Knowledge to Action framework was used as the conceptual framework for the
      research. RESULTS: Nurses who had taken a course in FSN reported a significantly
      more positive attitude towards involving families in their care after the ETI
      program compared to those who had not taken such a course. Furthermore, a
      majority of the nurses who participated in the ETI program reported that the
      program was a favorable experience and indicated readiness for applying FSN in
      clinical practice. CONCLUSIONS: Further research is needed regarding the benefits
      of offering FSN at an institutional level, but focusing international attention
      on effective strategies to implement FSN into nursing practice may result in
      better health care for individuals and families around the globe. CLINICAL
      RELEVANCE: Providing clinically meaningful education and training in family
      nursing through programs such as the ETI program for practicing nurses at a
      university hospital is essential in supporting nurses applying new knowledge,
      when providing evidence-based health care services, to individuals and their
      family members. Such training can facilitate integration of new and needed
      information in clinical practice.

PMID- 25369734
TI  - Genetic variation in retinal vascular patterning predicts variation in pial
      collateral extent and stroke severity.
AB  - The presence of a native collateral circulation in tissues lessens injury in
      occlusive vascular diseases. However, differences in genetic background cause
      wide variation in collateral number and diameter in mice, resulting in large
      variation in protection. Indirect estimates of collateral perfusion suggest that
      wide variation also exists in humans. Unfortunately, methods used to obtain these
      estimates are invasive and not widely available. We sought to determine whether
      differences in genetic background in mice result in variation in branch
      patterning of the retinal arterial circulation, and whether these differences
      predict strain-dependent differences in pial collateral extent and severity of
      ischemic stroke. Retinal patterning metrics, collateral extent, and infarct
      volume were obtained for 10 strains known to differ widely in collateral extent.
      Multivariate regression was conducted, and model performance was assessed using K
      fold cross-validation. Twenty-one metrics varied with strain (p<0.01). Ten
      metrics (e.g., bifurcation angle, lacunarity, optimality) predicted collateral
      number and diameter across seven regression models, with the best model closely
      predicting (p<0.0001) number (+/-1.2-3.4 collaterals, K-fold R2=0.83-0.98),
      diameter (+/-1.2-1.9 MUm, R2=0.73-0.88), and infarct volume (+/-5.1 mm3, R2=0.85
      0.87). An analogous set of the most predictive metrics, obtained for the middle
      cerebral artery (MCA) tree in a subset of the above strains, also predicted
      (p<0.0001) collateral number (+/-3.3 collaterals, K-fold R2=0.78) and diameter
      (+/-1.6 MUm, R2=0.86). Thus, differences in arterial branch patterning in the
      retina and the MCA trees are specified by genetic background and predict
      variation in collateral extent and stroke severity. If also true in human, and
      since genetic variation in cerebral collaterals extends to other tissues at least
      in mice, a similar "retinal predictor index" could serve as a non- or minimally
      invasive biomarker for collateral extent in brain and other tissues. This could
      aid prediction of severity of tissue injury in the event of an occlusive event or
      development of obstructive disease and in patient stratification for treatment
      options and clinical studies.

PMID- 25369735
TI  - Synthetic miR-145 mimic inhibits multiple myeloma cell growth in vitro and in
      vivo.
AB  - Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic
      strategies are required to combat this disease. It is well known that tumor
      suppressor microRNA (miRNA) acts as a new potential anticancer agent.
      Accumulating evidence showed that microRNA-145 (miR-145) is a candidate tumor
      suppressor miRNA. However, whether miR-145 is involved in the development and
      progression of MM reamins to be determined. In the present study, we investigated
      the therapeutic potential of synthetic miR-145 against human MM cells in vitro
      and in vivo. The results showed that miR-145 was reduced in MM tissues and cell
      lines. Enforced expression of miR-145 by transfection with miR-145 mimics
      inhibited cell proliferation, migration, and the invasion abilities of H929
      cells. Furthermore, our results demonstrated that the enforced expression of miR
      145 in H929 cells profoundly decreased the levels of p-AKT and p-PI3K, which may
      contribute to some extent to the inhibition of MM cell proliferation and
      survival. The enforced expression of miR-145 in a xenograft mouse model
      suppressed tumor growth. In conclusion, our findings suggested that miR-145 may
      act as a tumor suppressor and contributes to the progression of MM. Additionally,
      miR-145 mimics is a potential therapeutic agent for the treatment of MM.

PMID- 25369736
TI  - Dexmedetomidine versus midazolam for gastrointestinal endoscopy: a meta-analysis.
AB  - BACKGROUND AND AIM: Patients who undergo gastrointestinal endoscopy often require
      sedatives such as midazolam and the more recently developed alpha-2 agonist,
      dexmedetomidine. To assess the efficacy and safety of dexmedetomidine sedation
      for gastrointestinal endoscopy, we conducted a systematic review and meta
      analysis of randomized controlled trials comparing dexmedetomidine with
      midazolam. METHODS: We searched PubMed, the Cochrane library, and the Igaku-chuo
      zasshi database in order to identify randomized trials eligible for inclusion in
      our meta-analysis. Data from the eligible studies were combined to calculate
      pooled odds ratios (OR) or weighted mean differences (WMD). RESULTS: We
      identified nine randomized trials from the database search. Compared to that of
      midazolam, the pooled OR for restlessness of dexmedetomidine was 0.078 (95%
      confidence interval [CI]: 0.013-0.453, P < 0.0001), and there was no significant
      heterogeneity among the trial results. Dexmedetomidine significantly increased
      Ramsay sedation score compared with midazolam (WMD: 0.401, 95% CI: 0.110-0.692, P
      = 0.0069), without significant heterogeneity. Compared with midazolam, the pooled
      OR for hypoxia, hypotension, and bradycardia with dexmedetomidine sedation were
      0.454 (95% CI: 0.098-2.11), 1.370 (95% CI: 0.516-3.637), and 2.575 (95% CI: 0.978
      6.785), respectively, with no significant differences detected between the
      groups. CONCLUSION: This meta-analysis shows that dexmedetomidine is a safe and
      effective sedative agent for gastrointestinal endoscopy, especially endoscopic
      retrograde cholangiopancreatography and endoscopic submucosal dissection.

PMID- 25369739
TI  - Green photocatalytic organic transformations by polyoxometalates vs. mesoporous
      TiO2 nanoparticles: selective aerobic oxidation of alcohols.
AB  - In this study, the catalytic activity of decatungstate (W10O32(4-)) supported on
      mesoporous TiO2 nanoparticle assemblies (DT-MTA) was compared with that of
      homogeneous [Bu4N]4W10O32 catalysts under mild conditions. Our experiments showed
      that both catalytic systems achieve exceptionally high activity and selectivity
      under UV-visible light oxidation of various para-substituted aryl alcohols, using
      molecular oxygen as a "green" oxidant. The chemoselective transformation of aryl
      alcohols into the corresponding ketones was investigated with gas chromatography
      (GC) and NMR spectroscopy. Product analysis and kinetic results also indicated
      that these photooxidation reactions proceed via both electron transfer (ET) and
      hydrogen atom transfer (HAT) mechanisms over the DT-MTA catalyst, with the former
      one as the predominant, whereas a HAT route was adopted to account for the
      decatungstate homogeneous catalyzed reactions. 

PMID- 25369738
TI  - Small bowel mucosal damage in familial Mediterranean fever: results of capsule
      endoscopy screening.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is the most common form of
      autoinflammatory diseases. We aimed to evaluate the small bowel mucosa by capsule
      endoscopy (CE) in FMF patients for investigation of other possible causes of
      abdominal pain. MATERIAL AND METHODS: The study group consisted of 41 patients
      with FMF. A standard questionnaire was used to record the gastrointestinal
      symptoms, other clinical findings, Mediterranean fever gene (MEFV) mutations, and
      history of medications including non-steroidal anti-inflammatory drugs (NSAIDs).
      Gastroscopy, colonoscopy and small bowel CE were performed in all patients, and
      biopsies were taken from terminal ileum and duodenum. RESULTS: The mean age of
      the patients was 34 +/- 11 years, 63% of them were female, and 76.5% of them were
      carrying MEFV exon 10 mutations. Only one patient used NSAIDs in addition to
      colchicine. In endoscopic investigations, gastric erosion was detected in only
      one patient, and no significant findings were detected in colonoscopy. CE showed
      small bowel mucosal defects in 44% (erosions in 26.8%, ulcer in 17.1%) and edema
      in 29.3% of the patients. Most (64%) of the ulcer and erosions were localized to
      jejunum, and only 24% were in ileum. Mitotic changes as an indirect finding of
      colchicine toxicity were not different from the changes observed in samples of
      independent group of patients with irritable bowel syndrome. CONCLUSION: Mucosal
      defect was observed in half of the FMF patients, which may be associated with
      underlying inflammation or chronic colchicine exposure. Detection of nonspecific
      chronic inflammation without mitotic changes supports that mucosal defects may be
      associated with the autoinflammatory process.

PMID- 25369737
TI  - Reproductive assurance drives transitions to self-fertilization in experimental
      Caenorhabditis elegans.
AB  - BACKGROUND: Evolutionary transitions from outcrossing between individuals to
      selfing are partly responsible for the great diversity of animal and plant
      reproduction systems. The hypothesis of 'reproductive assurance' suggests that
      transitions to selfing occur because selfers that are able to reproduce on their
      own ensure the persistence of populations in environments where mates or
      pollination agents are unavailable. Here we test this hypothesis by performing
      experimental evolution in Caenorhabditis elegans. RESULTS: We show that self
      compatible hermaphrodites provide reproductive assurance to a male-female
      population facing a novel environment where outcrossing is limiting. Invasions of
      hermaphrodites in male-female populations, and subsequent experimental evolution
      in the novel environment, led to successful transitions to selfing and
      adaptation. Adaptation was not due to the loss of males during transitions, as
      shown by evolution experiments in exclusively hermaphroditic populations and in
      male-hermaphrodite populations. Instead, adaptation was due to the displacement
      of females by hermaphrodites. Genotyping of single-nucleotide polymorphisms
      further indicated that the observed evolution of selfing rates was not due to
      selection of standing genetic diversity. Finally, numerical modelling and
      evolution experiments in male-female populations demonstrate that the improvement
      of male fitness components may diminish the opportunity for reproductive
      assurance. CONCLUSIONS: Our findings support the hypothesis that reproductive
      assurance can drive the transition from outcrossing to selfing, and further
      suggest that the success of transitions to selfing hinges on adaptation of
      obligate outcrossing populations to the environment where outcrossing was once a
      limiting factor.

PMID- 25369740
TI  - Lymphotoxin beta receptor activation promotes bladder cancer in a nuclear factor
      kappaB-dependent manner.
AB  - Bladder cancer (BCa) is the most common tumor of the urinary system. Chronic
      inflammation in the papillary urothelial neoplasm of low malignant potential
      (PUNLMP)may contribute to carcinogenesis, including that of BCa, via poorly
      understood mechanisms. In this study, we show that the lymphotoxin beta receptor
      (LTbetaR) is upregulated in BCa via activation of the canonical and non-canonical
      nuclear factor-kappaB (NF-kappaB) pathways. The mRNA expression of LTbetaR in 81
      BCa, 10 chronic cystitis and 23 healthy bladder mucosa tissues was investigated
      by reverse transcription-fluorescent quantitative polymerase chain reaction (RT
      FQ-PCR), and protein expression was studied in 73 BCa, 30 cystitis and 15 healthy
      paraffin-embedded tissue sections by immunohistochemistry. Both LTbetaR mRNA and
      protein were upregulated in BCa and cystitis compared to the healthy group
      (P<0.05). The mRNA level of the downstream NF-kappaB canonical pathway p65 gene
      and of the non-canonical pathway RelB gene were higher in the BCa and cystitis
      groups compared to the healthy one. The level of phosphorylated p65 (p-p65)
      protein of the canonical NF-kappaB pathway and that of p52, a protein of the non
      canonical NF-kappaB pathway, were also higher in the BCa and cystitis group
      compared to the healthy group. The levels of these proteins significantly
      correlated to the pathological grade, clinical stage and lymph node metastasis of
      BCa patients (P<0.05). In addition, there was a positive correlation between
      LTbetaR and NF-kappaB pathway proteins. Thus, LTbetaR signaling may be involved
      in promoting BCa through the NF-kappaB pathway, and which may represent the
      molecular link between inflammation and BCa. 

PMID- 25369741
TI  - Cobalt nanoparticles embedded in N-doped carbon as an efficient bifunctional
      electrocatalyst for oxygen reduction and evolution reactions.
AB  - Cobalt based catalysts are promising bifunctional electrocatalysts for both
      oxygen reduction and oxygen evolution reactions (ORR and OER) in unitized
      regenerative fuel cells (URFCs) operating with alkaline electrolytes. Here we
      report a hybrid composite of cobalt nanoparticles embedded in nitrogen-doped
      carbon (Co/N-C) via a solvothermal carbonization strategy. With the synergistic
      effect arising from the N-doped carbon and cobalt nanoparticles in the composite,
      the Co/N-C hybrid catalyst exhibits highly efficient bifunctional catalytic
      activity and excellent stability toward both ORR and OER. The DeltaE (oxygen
      electrode activity parameter for judging the overall electrocatalytic activity of
      a bifunctional electrocatalyst) value for Co/N-C is 0.859 V, which is smaller
      than those of Pt/C and most of the non-precious metal catalysts in previous
      studies. Furthermore, the Co/N-C composite also shows better bifunctional
      catalytic activity than its oxidative counterparts, which could be attributed to
      the high specific surface area and the efficient charge transfer ability of the
      composite, as well as the good synergistic effect between N-doped carbon and the
      Co nanoparticles in the Co/N-C composite. 

PMID- 25369742
TI  - Magnetotactic bacteria from extreme environments.
AB  - Magnetotactic bacteria (MTB) represent a diverse collection of motile prokaryotes
      that biomineralize intracellular, membrane-bounded, tens-of-nanometer-sized
      crystals of a magnetic mineral called magnetosomes. Magnetosome minerals consist
      of either magnetite (Fe3O4) or greigite (Fe3S4) and cause cells to align along
      the Earth's geomagnetic field lines as they swim, a trait called magnetotaxis.
      MTB are known to mainly inhabit the oxic-anoxic interface (OAI) in water columns
      or sediments of aquatic habitats and it is currently thought that magnetosomes
      function as a means of making chemotaxis more efficient in locating and
      maintaining an optimal position for growth and survival at the OAI. Known
      cultured and uncultured MTB are phylogenetically associated with the Alpha-,
      Gamma- and Deltaproteobacteria classes of the phylum Proteobacteria, the
      Nitrospirae phylum and the candidate division OP3, part of the Planctomycetes
      Verrucomicrobia-Chlamydiae (PVC) bacterial superphylum. MTB are generally thought
      to be ubiquitous in aquatic environments as they are cosmopolitan in distribution
      and have been found in every continent although for years MTB were thought to be
      restricted to habitats with pH values near neutral and at ambient temperature.
      Recently, however, moderate thermophilic and alkaliphilic MTB have been described
      including: an uncultured, moderately thermophilic magnetotactic bacterium present
      in hot springs in northern Nevada with a probable upper growth limit of about 63 
      degrees C; and several strains of obligately alkaliphilic MTB isolated in pure
      culture from different aquatic habitats in California, including the hypersaline,
      extremely alkaline Mono Lake, with an optimal growth pH of >9.0. 

PMID- 25369743
TI  - Hot spring metagenomics.
AB  - Hot springs have been investigated since the XIX century, but isolation and
      examination of their thermophilic microbial inhabitants did not start until the
      1950s. Many thermophilic microorganisms and their viruses have since been
      discovered, although the real complexity of thermal communities was envisaged
      when research based on PCR amplification of the 16S rRNA genes arose. Thereafter,
      the possibility of cloning and sequencing the total environmental DNA, defined as
      metagenome, and the study of the genes rescued in the metagenomic libraries and
      assemblies made it possible to gain a more comprehensive understanding of
      microbial communities-their diversity, structure, the interactions existing
      between their components, and the factors shaping the nature of these
      communities. In the last decade, hot springs have been a source of thermophilic
      enzymes of industrial interest, encouraging further study of the poorly
      understood diversity of microbial life in these habitats. 

PMID- 25369744
TI  - Is struvite a prebiotic mineral?
AB  - The prebiotic relevance of mineral struvite, MgNH4PO4.6H2O, was studied
      experimentally as a phosphorylating reagent and, theoretically, to understand the
      geochemical requirements for its formation. The effectiveness of phosphorylation
      by the phosphate mineral, monetite, CaHPO4, was also studied to compare to the
      efficiency of struvite. The experiments focused on the phosphorylation reactions
      of the minerals with organic compounds, such as nucleosides, glycerol and choline
      chloride, and heat at 75  degrees C for about 7-8 days and showed up to 28%
      phosphorylation of glycerol. In contrast, the compositional requirements for the
      precipitation of struvite are high ammonium and phosphate concentrations, as well
      as a little Ca2+ dissolved in the water. Combined, these requirements suggest
      that it is not likely that struvite was present in excess on the early Earth to
      carry out phosphorylation reactions. The present study focuses on the
      thermodynamic aspects of struvite formation, complementing the results given by
      Orgel and Handschuh (1973), which were based on the kinetic effects. 

PMID- 25369746
TI  - Heterotrophic protists in hypersaline microbial mats and deep hypersaline basin
      water columns.
AB  - Although hypersaline environments pose challenges to life because of the low
      water content (water activity), many such habitats appear to support eukaryotic
      microbes. This contribution presents brief reviews of our current knowledge on
      eukaryotes of water-column haloclines and brines from Deep Hypersaline Anoxic
      Basins (DHABs) of the Eastern Mediterranean, as well as shallow-water hypersaline
      microbial mats in solar salterns of Guerrero Negro, Mexico and benthic
      microbialite communities from Hamelin Pool, Shark Bay, Western Australia. New
      data on eukaryotic diversity from Shark Bay microbialites indicates eukaryotes
      are more diverse than previously reported. Although this comparison shows that
      eukaryotic communities in hypersaline habitats with varying physicochemical
      characteristics are unique, several groups are commonly found, including diverse
      alveolates, strameonopiles, and fungi, as well as radiolaria. Many eukaryote
      sequences (SSU) in both regions also have no close homologues in public
      databases, suggesting that these environments host unique microbial eukaryote
      assemblages with the potential to enhance our understanding of the capacity of
      eukaryotes to adapt to hypersaline conditions. 

PMID- 25369745
TI  - Prebiotic chemistry: geochemical context and reaction screening.
AB  - The origin of life on Earth is widely believed to have required the reactions of
      organic compounds and their self- and/or environmental organization. What those
      compounds were remains open to debate, as do the environment in and process or
      processes by which they became organized. Prebiotic chemistry is the systematic
      organized study of these phenomena. It is difficult to study poorly defined
      phenomena, and research has focused on producing compounds and structures
      familiar to contemporary biochemistry, which may or may not have been crucial for
      the origin of life. Given our ignorance, it may be instructive to explore the
      extreme regions of known and future investigations of prebiotic chemistry, where
      reactions fail, that will relate them to or exclude them from plausible
      environments where they could occur. Come critical parameters which most deserve
      investigation are discussed. 

PMID- 25369748
TI  - Postinjury treatment with magnesium sulfate attenuates neuropathic pains
      following spinal cord injury in male rats.
AB  - Spinal cord injury (SCI) has a number of severe and disabling consequences
      including chronic pain. Approximately 40% of patients experience neuropathic
      pain, which appears to be persistent. Previous studies have demonstrated the
      neuroprotective effects of magnesium sulfate (MgSO4). We aimed to investigate the
      effect of MgSO4 on neuropathic pains following SCI in male rats. Thirty-two adult
      male rats (weight 300-350 g) were used. After laminectomy, a complete SCI was
      induced by compression of the spinal cord for 1 min with an aneurysm clip. A
      single dose of 300 or 600 mg/kg MgSO4 was injected intraperitoneally. Tail-flick
      latency and acetone drop test scores were evaluated before surgery and once a
      week for 4 weeks after surgery. Rats in groups SCI+Mg300 and SCI+Mg600 showed
      significantly higher mean tail-flick latencies and lower mean scores in the
      acetone test compared with those in the SCI+veh group 4 weeks after surgery
      (P<0.05). These findings revealed that systemic single-dose administration of
      MgSO4 can attenuate thermal hyperalgesia and cold allodynia induced by SCI in
      rats. 

PMID- 25369749
TI  - Comparison of 68Ga-DOTATATE PET-CT, 18F-FDG PET-CT and 99mTc-(V)DMSA scintigraphy
      in the detection of recurrent or metastatic medullary thyroid carcinoma.
AB  - PURPOSE: We aimed to compare the efficacies of gallium-68 (68Ga) DOTATATE PET
      computed tomography (CT), fluorine-18 fluorodeoxyglucose (18F-FDG) PET-CT and
      technetium-99m (99mTc)-(V)DMSA scintigraphy in the detection of
      residual/metastatic medullary thyroid carcinoma (MTC). MATERIALS AND METHOD: We
      retrospectively evaluated DOTATATE PET-CT, 18F-FDG PET-CT and (V)DMSA
      scintigraphy of 22 MTC patients, all taken within a 6-month period in each
      patient, because of high levels of calcitonin (Ct) and carcinoembryonic antigen
      (CEA). We investigated the relationships between the results of the imaging
      modalities and tumour marker levels and the sporadic versus hereditary nature of
      the disease, as well as the effect of imaging results on patient management.
      RESULTS: The ages of the patients at diagnosis were between 20 and 69 years. The
      median levels of Ct and CEA were 871.5 pg/ml and 11.2 ng/ml, respectively. In the
      patient-based analysis, we observed at least one focus of abnormal uptake in 15
      of 22 DOTATATE PET-CT (68.2% sensitivity), eight of 18 18F-FDG PET-CT (44.4%
      sensitivity) and five of 15 (V)DMSA scans (33.3% sensitivity). These data showed
      a significant difference between DOTATATE PET-CT and (V)DMSA scintigraphy
      (P=0.016), whereas the relationships between DOTATATE PET-CT and 18F-FDG PET-CT
      and between 18F-FDG PET-CT and (V)DMSA scintigraphy showed no significant
      differences (P>0.05). In the lesion-based analysis, 134 lesions were detected
      with DOTATATE PET-CT, 76 lesions with 18F-FDG PET-CT and nine lesions with
      (V)DMSA scintigraphy. CONCLUSION: DOTATATE PET-CT is an efficient imaging
      modality in MTC patients with increased Ct and CEA (especially >1000 pg/ml and 50
      ng/ml, respectively) for localizing recurrent or metastatic disease. 18F-FDG PET
      CT can be performed if DOTATATE PET-CT is not available, but (V)DMSA scintigraphy
      is not recommended.

PMID- 25369750
TI  - Contribution of 111In-pentetreotide SPECT/CT imaging to conventional somatostatin
      receptor scintigraphy in the detection of neuroendocrine tumours.
AB  - AIM: The aim of the study was to assess the contribution of 111In-pentetreotide
      single-photon emission computed tomography/computed tomography (SPECT/CT) imaging
      to conventional somatostatin receptor scintigraphy (SRS) in terms of lesion
      characterization and localization in the detection of neuroendocrine tumours
      (NETs). MATERIALS AND METHODS: A total of 107 patients with suspected or
      confirmed NET underwent SRS and SPECT/CT after the injection of 148-222 MBq of
      111In-pentetreotide. SRS and SPECT/CT images were interpreted independently. Each
      site of abnormal tracer uptake was recorded according to the anatomical
      localization, and as being consistent or not with NET. The findings were
      confirmed with pathological and/or clinical/imaging follow-up data. RESULTS: A
      final diagnosis of NET was achieved in 49/107 patients (45.8%). No evidence of
      NET was found in the rest. SPECT/CT resulted in a significant reduction of
      indeterminate cases [14/107 (13.1%) vs. 1/107 (0.9%); P<0.001] and correctly
      reclassified one patient as negative for NET and another as positive for NET.
      SPECT/CT had 87.8% sensitivity and 96.6% specificity on a patient-based analysis,
      statistically higher than SRS (P<0.001). A total of 160 foci were detected (108
      NETs and 52 physiological/benign tumours). SRS correctly classified 105/160 foci
      (65.6%) and remained inaccurate for 55 lesions. These 55 included 31
      indeterminate lesions, 12 lesions detected only by SPECT/CT and 12 false-positive
      lesions. The number of foci correctly classified on the SPECT/CT images was
      151/160 (94.4%), whereas two remained indeterminate and seven were false-positive
      findings. CONCLUSION: SPECT/CT provides incremental diagnostic value over SRS,
      mainly because of a precise anatomical localization that helps discriminate
      between tumour lesions and physiological uptake. SPECT/CT may detect unsuspected
      lesions in a small proportion of patients.

PMID- 25369752
TI  - Visualization of tissue alterations in thyroid nodules after microwave ablation:
      sonographic versus scintigraphic imaging.
AB  - OBJECTIVE: The aim of this study was to elucidate the potential of B-mode
      sonography, colour-coded Doppler sonography and scintigraphic imaging as
      diagnostic methods for the evaluation of treatment success and follow-up of
      thyroid nodules after microwave ablation. MATERIALS AND METHODS: Thirty-six
      thyroid nodules in 33 patients were subjected to microwave ablation and were
      evaluated by means of B-mode sonography, colour-coded Doppler sonography and
      scintigraphic imaging before and after ablation. B-mode sonography results were
      characterized by echogenicity that was assigned ultrasound scores (US).
      Hypoechoic nodules were referred to as US1, isoechoic as US2 and hyperechoic
      nodules as US3. Colour-coded Doppler sonography was evaluated by a scoring system
      reflecting the blood flow of ablated nodules. A Doppler score (DS) of 1 was
      assigned for nodules without blood flow, DS2 for those with an absence of
      intranodular but presence of perinodular blood flow and DS3 for nodules with
      intranodular and perinodular flow. Scintigraphic imaging was performed using
      technetium-99m pertechnetate (99mTc-pertechnetate) for pretherapeutic and post
      therapeutic imaging of indifferent nodules and 99mTc-methoxyisobutylisonitrile
      (99mTc-MIBI) as the tracer for cold nodules. RESULTS: B-mode sonography reflected
      decreased echogenicity and US [median decrease by Delta=1+/-0.6 (P<0.01)] after
      ablation. Colour-coded Doppler sonography showed declined blood flow; median
      reduction of DS was Delta=1+/-0.7 (P<0.01). In scintigraphic imaging, tracer
      uptake reduced by a median 42.5+/-27.8% (P<0.01). 99mTc-pertechnetate scans
      recorded tracer uptake reduction by 32.3+/-17.8%, and 99mTc-MIBI scans showed
      uptake reduction in ablated regions by 56.1+/-29.7%. CONCLUSION: B-mode
      sonography and colour-coded Doppler sonography are easily applicable, providing
      real-time imaging control for microwave ablation. However, they are limited in
      accuracy and susceptible to artefacts. Scintigraphic imaging delivers
      quantifiable, operator-independent results and is promising in the evaluation of
      treatment success and follow-up.

PMID- 25369751
TI  - Volumetric comparison of positron emission tomography/computed tomography using
      4'-[methyl-11C]-thiothymidine with 2-deoxy-2-18F-fluoro-D-glucose in patients
      with advanced head and neck squamous cell carcinoma.
AB  - OBJECTIVE: We prospectively compared the diagnostic value of PET/computed
      tomography (CT) findings using the tracers 4'-[methyl-11C]-thiothymidine (11C
      4DST) and 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) in patients with head and neck
      squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Thirty-eight patients with
      advanced HNSCC underwent 11C-4DST PET/CT and 18F-FDG PET/CT before treatment.
      Maximum standardized uptake values (SUVmax) were measured for both PET/CT
      studies; in addition, total lesion glycolysis (TLG) of 18F-FDG PET/CT and total
      lesion proliferation (TLP) of 11C-4DST PET/CT were measured. Absolute TLG and TLP
      values as well as values with various SUV thresholds were measured. All patients
      were followed up for 13.5+/-7.5 months (mean+/-SD) to monitor recurrence.
      RESULTS: A statistically significant correlation was observed between the primary
      tumor SUVmax for 11C-4DST PET/CT and 18F-FDG PET/CT (r=0.46, P<0.01). TLP values
      with SUV thresholds strongly correlated with TLG values relative to the same
      thresholds (r=0.60-0.92, P<0.001). Nine of the 38 patients with post-treatment
      recurrence were identified. Receiver operating characteristic curves for TLG3.0
      and TLP2.5 showed the highest prognostic ability for recurrence; the sensitivity
      and specificity of TLG3.0 were 89 and 72%, respectively, and the sensitivity and
      specificity of TLP2.5 were 89 and 55%, respectively. CONCLUSION: In patients with
      advanced HNSCC, the TLP of 11C-4DST PET/CT strongly correlated with the TLG of
      18F-FDG PET/CT. Although there were no large differences between these values,
      the receiver operating characteristic curves of the absolute TLG had slightly
      better prognostic ability for recurrence.

PMID- 25369747
TI  - Endocannabinoids and striatal function: implications for addiction-related
      behaviours.
AB  - Since the identification and cloning of the major cannabinoid receptor expressed
      in the brain almost 25 years ago research has highlighted the potential of drugs
      that target the endocannabinoid system for treating addiction. The
      endocannabinoids, anandamide and 2-arachidonoyl glycerol, are lipid-derived
      metabolites found in abundance in the basal ganglia and other brain areas
      innervated by the mesocorticolimbic dopamine systems. Cannabinoid CB1 receptor
      antagonists/inverse agonists reduce reinstatement of responding for cocaine,
      alcohol and opiates in rodents. However, compounds acting on the endocannabinoid
      system may have broader application in treating drug addiction by ameliorating
      associated traits and symptoms such as impulsivity and anxiety that perpetuate
      drug use and interfere with rehabilitation. As a trait, impulsivity is known to
      predispose to addiction and facilitate the emergence of addiction to stimulant
      drugs. In contrast, anxiety and elevated stress responses accompany extended drug
      use and may underlie the persistence of drug intake in dependent individuals. In
      this article we integrate and discuss recent findings in rodents showing
      selective pharmacological modulation of impulsivity and anxiety by cannabinoid
      agents. We highlight the potential of selective inhibitors of endocannabinoid
      metabolism, directed at fatty acid amide hydrolase and monoacylglycerol lipase,
      to reduce anxiety and stress responses, and discuss novel mechanisms underlying
      the modulation of the endocannabinoid system, including the attenuation of
      impulsivity, anxiety, and drug reward by selective CB2 receptor agonists. 

PMID- 25369753
TI  - Validation and impact of a new technique for assessment of glomerular filtration
      rate in patients with liver disease.
AB  - OBJECTIVES: Previously we have proposed a technique for the measurement of plasma
      clearance in patients with ascites. The impact of using the technique was
      assessed and the results compared with those from a reference technique in 111
      patients having glomerular filtration rate measurements as part of their workup
      for liver transplantation. METHODS: Results of calculations using the new
      technique were compared with plasma clearance measurements obtained using a
      conventional slope-intercept technique and with clearance measurements based on
      urine collection. Discrepancies between the results of plasma clearance and
      urinary clearance assessments were investigated by using an uncollimated gamma
      camera to measure the total retention of the tracer. RESULTS: Conventional slope
      intercept calculations overestimated clearance compared with the new technique by
      more than 20% in 21% of the patients. Significant differences between the results
      of the two methods were more likely in patients with more severe ascites. Results
      of urine collection-based measurements of Cr-51 EDTA clearance were frequently
      significantly lower than measurements using the new technique, whereas
      measurements of urinary clearance of creatinine were higher. Gamma camera
      measurements suggest that discrepancies between total and urinary clearance of Cr
      51 EDTA are due to incomplete urine collection. CONCLUSION: The new technique is
      a practical method for assessment of kidney function and should be used in
      patients with liver disease who have or may have ascites.

PMID- 25369754
TI  - Diethylnitrosamine-induced cirrhosis in Wistar rats: an experimental feasibility
      study.
AB  - The experimental models of the development of cirrhosis in rats require a long
      time. Many studies in animals have demonstrated similarities in histological
      pattern with human cirrhosis. Just like the relation between cirrhosis and
      increased lipid peroxidation (LPO), which contributes to the worsening of the
      disease. However, few studies have focused on the reduction of time to establish
      cirrhosis and evaluated the expression of heat-shock protein 70 (HSP70) in
      cirrhotic livers of rodents. The present study proposes the adaptation of an
      experimental cirrhosis model using diethylnitrosamine (DEN). Twenty-six male
      Wistar rats, weighing +/-270 g, divided into two groups: (i) CO-control and (ii)
      DEN-diethylnitrosamine. The DEN group received 50 mg/kg of DEN twice a week
      intraperitoneally for 7 weeks. The model developed cirrhosis in 7 weeks. The
      liver function tests showed that the animals with DEN-induced cirrhosis had
      increased levels when compared to control. The histological examination showed
      changes in the liver architecture, with severe ductal proliferation, signs of
      chronic damage, cholestasis, lymphocytic infiltrate, steatosis, and extensive
      parenchymal loss. We also found nodular formations with homogeneous pattern,
      increased LPO, increased expression of iNOS, TGF beta, alpha-SMA, and NQO1.
      However, the HSP70 expression was reduced in cirrhotic animals. This study showed
      signs of cirrhosis in liver based on biochemical, histological, and molecular
      analysis. The reduced expression of HSP70 appears to be associated with increased
      oxidative stress, contributing to the worsening of the disease.

PMID- 25369755
TI  - Restructuring care for older adults undergoing surgery: preliminary data from the
      Co-Management of Older Operative Patients En Route Across Treatment Environments
      (CO-OPERATE) model of care.
AB  - Surgery is common in older adults, so geriatric and surgical providers need to
      develop expertise in the care of older adults undergoing surgery. The Co
      management of Older Operative Patients En Route Across Treatment Environments (CO
      OPERATE) program is a clinical and educational collaboration between geriatrics
      and several surgical specialties at Veterans Affairs Health Care Connecticut.
      Individuals in CO-OPERATE are co-managed during the pre-, peri-, and
      postoperative periods. General surgery, urology, vascular surgery, orthopedics,
      cardiothoracic surgery and neurosurgery all participate in the program, with
      geriatrics expertise provided by a geriatrician, geriatric nurse practitioner and
      a geriatric clinical pharmacist. In the initial 3 years, there were 211 CO
      OPERATE participants; 31% were evaluated preoperatively, and 62% of the
      individuals seen preoperatively were seen in clinic. There was a median of three
      recommendations per consultation. At discharge, 56% returned to the community.
      Individuals seen preoperatively were more likely to return to the community (63%)
      than those seen after surgery (50%, P = .10). Geriatrics co-management with a
      variety of surgical specialties is feasible and may be associated with higher
      rates of discharge back to the community.

PMID- 25369756
TI  - Multiphasic modelling of bone-cement injection into vertebral cancellous bone.
AB  - Percutaneous vertebroplasty represents a current procedure to effectively
      reinforce osteoporotic bone via the injection of bone cement. This contribution
      considers a continuum-mechanically based modelling approach and simulation
      techniques to predict the cement distributions within a vertebra during
      injection. To do so, experimental investigations, imaging data and image
      processing techniques are combined and exploited to extract necessary data from
      high-resolution MUCT image data. The multiphasic model is based on the Theory of
      Porous Media, providing the theoretical basis to describe within one set of
      coupled equations the interaction of an elastically deformable solid skeleton, of
      liquid bone cement and the displacement of liquid bone marrow. The simulation
      results are validated against an experiment, in which bone cement was injected
      into a human vertebra under realistic conditions. The major advantage of this
      comprehensive modelling approach is the fact that one can not only predict the
      complex cement flow within an entire vertebra but is also capable of taking into
      account solid deformations in a fully coupled manner. The presented work is the
      first step towards the ultimate and future goal of extending this framework to a
      clinical tool allowing for pre-operative cement distribution predictions by means
      of numerical simulations.

PMID- 25369757
TI  - Chloroquine inhibits MGC803 gastric cancer cell migration via the Toll-like
      receptor 9/nuclear factor kappa B signaling pathway.
AB  - Stimulation of Toll-like receptor 9 (TLR9) has been associated with invasion in
      various types of cancer cell in vitro. The present study aimed to evaluate the
      expression of TLR9 in MGC803 gastric cancer cells and investigate the effect of a
      non-specific TLR9 inhibitor, chloroquine (CQ), on MGC803 cell migration via the
      TLR9/nuclear factor kappa B (NFkappaB) signaling pathway. The expression of TLR9
      was investigated using reverse transcription polymerase chain reaction (RT-PCR),
      flow cytometry and western blot analysis. The effects of CQ on MGC803 cell
      proliferation were measured by MTT colorimetric assay. The mRNA expression levels
      of cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP)-2, MMP-7 and NFkappaB
      p65 were evaluated by RT-PCR in MGC803 cells stimulated by various concentrations
      of CQ. The migration of gastric cancer cells treated with CQ at 12, 24 and 36 h
      was measured by wound healing assay. The results indicated that MGC803 cells
      expressed TLR9 and that CQ had anti-proliferative effects on MGC803 cells and
      inhibited mRNA expression of COX-2, MMP-2, MMP-7 and NFkappaB p65 (P<0.05).
      Furthermore, CQ inhibited the bioactivity of NFkappaB p65 and prevented the
      migration of MGC803 cells in a dose-dependent manner (P<0.05). In conclusion, the
      results indicated that the TLR9/NFkappaB signaling pathway was involved in
      gastric cancer cell migration and that CQ had anti-tumor activity.

PMID- 25369759
TI  - Carbon monoxide bonding with BeO and BeCO3 : surprisingly high CO stretching
      frequency of OCBeCO3.
AB  - The complexes OCBeCO3 and COBeCO3 have been isolated in a low-temperature neon
      matrix. The more stable isomer OCBeCO3 has a very high C?O stretching mode of
      2263 cm(-1) , which is blue-shifted by 122 cm(-1) with respect to free CO and 79
      cm(-1) higher than in OCBeO. Bonding analysis of the complexes shows that OCBeO
      has a stronger OC?BeY bond than OCBeCO3 because it encounters stronger pi
      backdonation. The isomers COBeCO3 and COBeO exhibit red-shifted C?O stretching
      modes with respect to free CO. The inverse change of C?O stretching frequency in
      OC?BeY and CO?BeY is explained with the reversed polarization of the sigma and pi
      bonds in CO. 

PMID- 25369758
TI  - POEMS syndrome, calciphylaxis and focal segmental glomerulosclerosis - VEGF as a
      possible link.
AB  - BACKGROUND: Polyneuropathy organomegaly endocrinopathy M-protein skin changes
      (POEMS) syndrome is a rare cause of polyneuropathy. Calciphylaxis, a severe
      disease leading to necrotic ulcers of the skin, is associated with POEMS syndrome
      and also with renal disease. This case report describes a patient with POEMS
      syndrome plus primary focal segmental glomerulosclerosis. CASE PRESENTATION: A 27
      year-old Caucasian woman with chronic renal insufficiency due to focal segmental
      glomerulosclerosis and calciphylaxis presented to our institution with
      polyneuropathy and encephalopathy. An extensive diagnostic workup revealed POEMS
      syndrome. Serum concentrations of vascular endothelial growth factor (VEGF) were
      highly elevated, consistent with POEMS syndrome. CONCLUSION: To our knowledge,
      this is the first report of a patient with POEMS syndrome and primary focal
      segmental glomerulosclerosis. The combination of POEMS syndrome, calciphylaxis
      and primary focal segmental glomerulosclerosis may be coincidental, suggesting
      the need for additional studies to confirm or exclude this association. VEGF may
      be an important pathogenetic link, suggesting that treatment with antiangiogenic
      agents may improve patient outcomes.

PMID- 25369761
TI  - Effects of glucosamine and chondroitin supplementation on knee osteoarthritis: an
      analysis with marginal structural models.
AB  - OBJECTIVE: The purpose of this study was to estimate the effectiveness of the
      combination of glucosamine and chondroitin in relieving knee symptoms and slowing
      disease progression among patients with knee osteoarthritis (OA). METHODS: The 4
      year followup data from the Osteoarthritis Initiative data set were analyzed. We
      used a "new-user" design, for which only participants who were not using
      glucosamine/chondroitin at baseline were included in the analyses (n = 1,625).
      Cumulative exposure was calculated as the number of visits when participants
      reported use of glucosamine/chondroitin. Knee symptoms were measured with the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and
      structural progression was determined by measuring the joint space width (JSW).
      To control for the time-varying confounders that might be influenced by previous
      treatments, we used marginal structural models to estimate the effects on OA of
      using glucosamine/chondroitin for 3 years, 2 years, and 1 year. RESULTS: During
      the study period, 18% of the participants initiated treatment with
      glucosamine/chondroitin. After adjustment for potential confounders with marginal
      structural models, we found no clinically significant differences between users
      at all assessments and never-users of glucosamine/chondroitin in WOMAC pain (beta
      = 0.68 [95% confidence interval (95% CI) -0.16 to 1.53]), WOMAC stiffness (beta =
      0.41 [95% CI 0 to 0.82]), and WOMAC function (beta = 1.28 [95% CI -1.23 to 3.79])
      or JSW (beta = 0.11 [95% CI -0.21 to 0.44]). CONCLUSION: Use of
      glucosamine/chondroitin did not appear to relieve symptoms or modify disease
      progression among patients with radiographically confirmed OA. Our findings are
      consistent with the results of meta-analyses of clinical trials and extend those
      results to a more general population with knee OA.

PMID- 25369762
TI  - Trait differences between naturalized and invasive plant species independent of
      residence time and phylogeny.
AB  - The ability to predict which alien plants will transition from naturalized to
      invasive prior to their introduction to novel regions is a key goal for
      conservation and has the potential to increase the efficacy of weed risk
      assessment (WRA). However, multiple factors contribute to plant invasion success
      (e.g., functional traits, range characteristics, residence time, phylogeny), and
      they all must be taken into account simultaneously in order to identify
      meaningful correlates of invasion success. We compiled 146 pairs of
      phylogenetically paired (congeneric) naturalized and invasive plant species in
      Australia with similar minimum residence times (i.e., time since introduction in
      years). These pairs were used to test for differences in 5 functional traits
      (flowering duration, leaf size, maximum height, specific leaf area [SLA], seed
      mass) and 3 characteristics of species' native ranges (biome occupancy, mean
      annual temperature, and rainfall breadth) between naturalized and invasive
      species. Invasive species, on average, had larger SLA, longer flowering periods,
      and were taller than their congeneric naturalized relatives. Invaders also
      exhibited greater tolerance for different environmental conditions in the native
      range, where they occupied more biomes and a wider breadth of rainfall and
      temperature conditions than naturalized congeners. However, neither seed mass nor
      leaf size differed between pairs of naturalized and invasive species. A key
      finding was the role of SLA in distinguishing between naturalized and invasive
      pairs. Species with high SLA values were typically associated with faster growth
      rates, more rapid turnover of leaf material, and shorter lifespans than those
      species with low SLA. This suite of characteristics may contribute to the ability
      of a species to transition from naturalized to invasive across a wide range of
      environmental contexts and disturbance regimes. Our findings will help in the
      refinement of WRA protocols, and we advocate the inclusion of quantitative
      traits, in particular SLA, into the WRA schemes.

PMID- 25369763
TI  - Associations of self-perceived successful aging in young-old versus old-old
      adults.
AB  - BACKGROUND: The aim of this research was to compare associations of self
      perceived successful aging (SPSA) among Young-Old (Y-O; age 50-74 years) versus
      Old-Old (O-O; 75-99 years) community-dwelling adults. To our knowledge, this is
      the first study to compare respondents' self-perceptions of successful aging
      among O-O relative to Y-O adults. METHODS: Participants included 365 Y-O and 641
      O-O adults. The two age groups were compared in terms of the association of SPSA
      with other preselected measures including sociodemographic information, physical
      and mental functioning, objective and subjective cognitive functioning, emotional
      health, and positive psychological constructs. RESULTS: The O-O group reported
      higher levels of SPSA than the Y-O group. In multiple regression modeling
      examining predictors of SPSA in each group, there was a tendency toward lower
      associations in the O-O group overall. Most notably, the associations between
      physical and mental functioning with SPSA were significantly lower in the O-O
      versus Y-O group. There were no associations with SPSA that were significantly
      higher in the O-O versus Y-O group. CONCLUSION: The lower predictive power of
      physical and mental functioning on SPSA among O-O relative to Y-O adults is
      particularly noteworthy. It is apparent that SPSA is a multidimensional construct
      that cannot be defined by physical functioning alone. Continuing to clarify the
      underlying factors impacting SPSA between groups may inform tailored
      interventions to promote successful aging in Y-O and O-O adults.

PMID- 25369764
TI  - ERP and pupil responses to deviance in an oddball paradigm.
AB  - We investigated the relationship between, and functional significance of, P300,
      novelty P3, and the pupil dilation response (PDR). Subjects categorized stimuli
      including (a) words of a frequent category, (b) words of an infrequent category
      (14%), and (c) pictures of the frequent category ("novels"; 14%). The P300 and
      novelty P3 were uncorrelated with the PDR and differed in their response to
      experimental manipulation. Therefore, although the three physiological responses
      often co-occur, they appear to each manifest a distinct function: The PDR may be
      more closely linked to aspects of behavioral responding than the event-related
      potentials. Within participants, P300 and PDR latencies accounted for unique
      portions of the reaction time variance, and amplitudes of all three responses
      were larger for stimuli recalled on a subsequent test, compared to not recalled.
      We discuss the possibility that all three responses reflect norepinephric input
      from the locus coeruleus. 

PMID- 25369765
TI  - Nonsurgical separation of complete labial fusion using a Hegar dilator in
      postmenopausal women.
AB  - INTRODUCTION AND HYPOTHESIS: Labial fusion is a rare condition in postmenopausal
      women. The cause is unknown but is associated with low estrogen levels and
      chronic vulval inflammation. The aim of this video is to demonstrate the
      nonsurgical separation of labia using blunt dissection with a Hegar dilator in
      postmenopausal women with complete labia fusion. METHODS: Two postmenopausal
      women with urinary incontinence and voiding difficulty secondary to complete
      fusion of labia minora failed estrogen treatment and underwent labial separation
      using serial Hegar dilators to restore normal introital anatomy. Medical
      treatment with estrogen and digital massage was administered after surgery to
      avoid recurrence. RESULTS: Nonsurgical separation of labia is appropriate in
      postmenopausal women with complete labia minora fusion when medical treatment
      fails.

PMID- 25369766
TI  - A systematic nomenclature for mammalian tropomyosin isoforms.
AB  - Tropomyosin, a ubiquitous protein in animals and fungi, is associated with the
      actin cytoskeleton and is involved with stabilising actin filaments and
      regulating the interaction of the filament with other actin binding proteins. The
      protein is best known for its role in regulating the interaction between actin
      and myosin in muscle contraction but in recent years its role as a major player
      in the organisation and dynamics of the cytoskeleton has been increasingly
      recognised. In mammals Tpm is expressed from four distinct genes and alternate
      splicing of each gene can produce a total of up to 40 different mRNA variants
      most of which are expressed as proteins. We are expecting a renaissance in the
      study of tropomyosins as the roles of these different isoforms are beginning to
      be deciphered. However, it is our belief that such a renaissance is being limited
      by confusion over the naming systems for the tropomyosin isoforms. These result
      in even experienced workers struggling to reconcile work done in different
      laboratories and at different times. We propose here a systematic nomenclature
      for tropomyosin based on the best current practice. We recommend the adoption of
      these names and a cross-reference to the table of alternate names and accession
      numbers for protein sequences is included here. The National Center for
      Biotechnology Information (NCBI) website has been amended to include the
      nomenclature for the human, mouse and rat genes. 

PMID- 25369767
TI  - Enhanced efficacy of the CDNF/MANF family by combined intranigral overexpression
      in the 6-OHDA rat model of Parkinson's disease.
AB  - Cerebral Dopamine Neurotrophic Factor (CDNF) and Mesencephalic Astrocyte-derived
      Neurotrophic factor (MANF) are members of a recently discovered family of
      neurotrophic factors (NTFs). Here, we used intranigral or intrastriatal
      lentiviral vector-mediated expression to evaluate their efficacy at protecting
      dopaminergic function in the 6-OHDA model of Parkinson's disease (PD). In
      contrast to the well-studied Glial-Derived Neurotrophic Factor (GDNF), no
      beneficial effects were demonstrated by striatal overexpression of either
      protein. Interestingly, nigral overexpression of CDNF decreased amphetamine
      induced rotations and increased tyroxine hydroxylase (TH) striatal fiber density
      but had no effect on numbers of TH(+) cells in the SN. Nigral MANF overexpression
      had no effect on amphetamine-induced rotations or TH striatal fiber density but
      resulted in a significant preservation of TH(+) cells. Combined nigral
      overexpression of both factors led to a robust reduction in amphetamine-induced
      rotations, greater increase in striatal TH-fiber density and significant
      protection of TH(+) cells in the SN. We conclude that nigral CDNF and MANF
      delivery is more efficacious than striatal delivery. This is also the first study
      to demonstrate that combined NTF can have synergistic effects that result in
      enhanced neuroprotection, suggesting that multiple NTF delivery may be more
      efficacious for the treatment of PD than the single NTF approaches attempted so
      far. 

PMID- 25369768
TI  - PTEN depletion decreases disease severity and modestly prolongs survival in a
      mouse model of spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is the second most common genetic cause of death in
      childhood. However, no effective treatment is available to halt disease
      progression. SMA is caused by mutations in the survival motor neuron 1 (SMN1)
      gene. We previously reported that PTEN depletion leads to an increase in survival
      of SMN-deficient motor neurons. Here, we aimed to establish the impact of PTEN
      modulation in an SMA mouse model in vivo. Initial experiments using intramuscular
      delivery of adeno-associated vector serotype 6 (AAV6) expressing shRNA against
      PTEN in an established mouse model of severe SMA (SMNDelta7) demonstrated the
      ability to ameliorate the severity of neuromuscular junction pathology.
      Subsequently, we developed self-complementary AAV9 expressing siPTEN (scAAV9
      siPTEN) to allow evaluation of the effect of systemic suppression of PTEN on the
      disease course of SMA in vivo. Treatment with a single injection of scAAV9-siPTEN
      at postnatal day 1 resulted in a modest threefold extension of the lifespan of
      SMNDelta7 mice, increasing mean survival to 30 days, compared to 10 days in
      untreated mice. Our data revealed that systemic PTEN depletion is an important
      disease modifier in SMNDelta7 mice, and therapies aimed at lowering PTEN
      expression may therefore offer a potential therapeutic strategy for SMA. 

PMID- 25369769
TI  - Traceability of biologicals: present challenges in pharmacovigilance.
AB  - INTRODUCTION: Traceability is important in the postmarketing surveillance of
      biologicals, since changes in the manufacturing process may give rise to product-
      or batch-specific risks. With the expected expansion of the biosimilar market,
      there have been concerns about the ability to trace individual products within
      pharmacovigilance databases. AREAS COVERED: The authors discuss the present
      challenges in the traceability of biologicals in relation to pharmacovigilance,
      by exploring the processes involved in ensuring traceability. They explore both
      the existing systems that are in place for the recording of exposure information
      in clinical practice, as well as the critical steps involved in the transfer of
      exposure data to various pharmacovigilance databases. EXPERT OPINION: The
      existing systems ensure the traceability of biologicals down to the manufacturer
      within pharmacy records, but do not support the routine recording of batch
      information. Expected changes in supply chain standards provide opportunities to
      systematically record detailed exposure information. Spontaneous reporting
      systems are the most vulnerable link in ensuring traceability, due to the manual
      nature of data transfer. Efforts to improve the traceability should, in the short
      term, be focused toward encouraging health professionals and patients to
      systematically record and report detailed exposure information. Long-term
      solutions lie in expanding the accessibility to, and increasing the electronic
      exchange of exposure data.

PMID- 25369770
TI  - High-throughput sequencing of fecal DNA to identify insects consumed by wild
      Weddell's saddleback tamarins (Saguinus weddelli, Cebidae, Primates) in Bolivia.
AB  - The genus Saguinus represents a successful radiation of over 20 species of small
      bodied New World monkeys. Studies of the tamarin diet indicate that insects and
      small vertebrates account for ~16-45% of total feeding and foraging time, and
      represent an important source of lipids, protein, and metabolizable energy.
      Although tamarins are reported to commonly consume large-bodied insects such as
      grasshoppers and walking sticks (Orthoptera), little is known concerning the
      degree to which smaller or less easily identifiable arthropod prey comprises an
      important component of their diet. To better understand tamarin arthropod feeding
      behavior, fecal samples from 20 wild Bolivian saddleback tamarins (members of
      five groups) were collected over a 3 week period in June 2012, and analyzed for
      the presence of arthropod DNA. DNA was extracted using a Qiagen stool extraction
      kit, and universal insect primers were created and used to amplify a ~280 bp
      section of the COI mitochondrial gene. Amplicons were sequenced on the Roche 454
      sequencing platform using high-throughput sequencing techniques. An analysis of
      these samples indicated the presence of 43 taxa of arthropods including 10
      orders, 15 families, and 12 identified genera. Many of these taxa had not been
      previously identified in the tamarin diet. These results highlight molecular
      analysis of fecal DNA as an important research tool for identifying anthropod
      feeding patterns in primates, and reveal broad diversity in the taxa, foraging
      microhabitats, and size of arthropods consumed by tamarin monkeys.

PMID- 25369771
TI  - Ureaplasma species and Mycoplasma hominis in cervical fluid of pregnancies
      complicated by preterm prelabor rupture of membranes.
AB  - OBJECTIVE: To evaluate Ureaplasma species and Mycoplasma hominis DNA in the
      cervical fluid and their association with microbial invasion of the amniotic
      cavity (MIAC) and/or histological chorioamnionitis (HCA) in pregnancies
      complicated by preterm prelabor rupture of membranes (PPROM). STUDY DESIGN: A
      prospective study of 68 women with singleton pregnancies complicated by PPROM
      between 24(0/7) and 36(6/7) weeks was conducted. Cervical fluid and amniotic
      fluid were collected from all women at the time of admission. The Ureaplasma
      species and Mycoplasma hominis DNA in the cervical fluid were identified using
      specific real-time PCR. RESULTS: Ureaplasma species and Mycoplasma hominis DNA
      were identified in 59% (40/69) of the cervical fluid samples. Women with the
      presence of Ureaplasma species DNA with and without Mycoplasma hominis DNA in the
      cervical fluid had a higher rate of MIAC alone [35% (14/40) versus 11% (3/28); p
      = 0.02] and a higher rate of the presence of both MIAC and HCA [30% (12/40)
      versus 4% (1/28); p = 0.01] than women without Ureaplasma species and Mycoplasma
      hominis DNA in the cervical fluid. CONCLUSIONS: The presence of Ureaplasma
      species DNA with and without Mycoplasma hominis DNA in the cervical fluid is
      associated with a higher risk of MIAC or MIAC and HCA together in pregnancies
      complicated by PPROM.

PMID- 25369772
TI  - Novel Inhibitory Effects of Glycyrrhizic Acid on the Accumulation of Advanced
      Glycation End Product and Its Receptor Expression.
AB  - Beneficial effects of glycyrrhizic acid (GA), a bioactive extract of licorice
      root, in the prevention of metabolic syndrome have been consistently reported
      while advanced glycation end products (AGE) and receptor for advanced glycation
      end product (RAGE) are the leading factors in the development of diabetes
      mellitus. The aim of this study was to investigate the effects of GA on the AGE
      RAGE axis using high-fat/high-sucrose (HF/HS) diet-induced metabolic syndrome rat
      models. Twenty four male Sprague-Dawley rats were randomly assigned into three
      groups for 4 weeks: (1) Group A, normal diet with standard rat chow; (2) Group B,
      HF/HS diet; (3) Group C, HF/HS diet and oral administration of 100 mg/kg GA per
      day. The results showed that HF/HS diet elevated the fasting blood glucose level
      and insulin resistance index which was prevented by GA supplementation. GA
      treatment significantly lowered the circulating AGE independent of its glucose
      lowering effect. HF/HS diet also triggered RAGE upregulation in the abdominal
      muscles while GA administration downregulated RAGE expression in the abdominal
      muscles, aorta and subcutaneous adipose tissues. In conclusion, HF/HS diet could
      cause glucose intolerance, insulin resistance and upregulation of RAGE expression
      while GA ameliorated the metabolic dysregulation besides exhibiting inhibitory
      effects on the AGE-RAGE axis. 

PMID- 25369773
TI  - Integrin-targeted delivery into cancer cells of a Pt(IV) pro-drug through
      conjugation to RGD-containing peptides.
AB  - Conjugates of a Pt(IV) derivative of picoplatin with monomeric (Pt-c(RGDfK), 5)
      and tetrameric (Pt-RAFT-{c(RGDfK)}4, 6) RGD-containing peptides were synthesized
      with the aim of exploiting their selectivity and high affinity for alphaVbeta3
      and alphaVbeta5 integrins for targeted delivery of this anticancer metallodrug to
      tumor cells overexpressing these receptors. Solid- and solution-phase approaches
      in combination with click chemistry were used for the preparation of the
      conjugates, which were characterized by high resolution ESI MS and NMR.
      alphaVbeta3 and alphaVbeta5 integrin expression was evaluated in a broad panel of
      human cancer and non-malignant cells. SK-MEL-28 melanoma cells were selected
      based on the high expression levels of both integrins, while CAPAN-1 pancreatic
      cancer cells and 1BR3G fibroblasts were selected as the negative control.
      Internalization experiments revealed a good correlation between integrin
      expression and the cellular uptake of the corresponding fluorescein-labeled
      peptides and that the internalization capacity of the tetrameric RGD-containing
      peptide was considerably higher than that of the monomeric one. Cytotoxic
      experiments indicated that the antitumor activity of picoplatin in melanoma cells
      was increased by 2.6-fold when its Pt(IV) derivative was conjugated to c(RGDfK)
      (IC50 = 12.8 +/- 2.1 MUM) and by 20-fold when conjugated to RAFT-{c(RGDfK)}4
      (IC50 = 1.7 +/- 0.6 MUM). In contrast, the cytotoxicity of the conjugates was
      inhibited in control cells lacking alphaVbeta3 and alphaVbeta5 integrin
      expression. Finally, cellular uptake studies by ICP-MS confirmed a good
      correlation between the levels of expression of integrins, intracellular platinum
      accumulation and antitumor activity. Indeed, accumulation and cytotoxicity were
      much higher in SK-MEL-28 cells than in CAPAN-1, being particularly higher in the
      case of the tetrameric conjugate. The overall results highlight that the great
      ability of RAFT-{c(RGDfK)}4 to bind to and to be internalized by integrins
      overexpressed in SK-MEL-28 cells results in higher accumulation of the Pt(IV)
      complex, leading to a high antitumor activity. These studies provide new insights
      into the potential of targeting alphaVbeta3 and alphaVbeta5 integrins with Pt(IV)
      anticancer pro-drugs conjugated to tumor-targeting devices based on RGD
      containing peptides, particularly on how multivalency can improve both the
      selectivity and potency of such metallodrugs by increasing cellular accumulation
      in tumor tissues.

PMID- 25369774
TI  - Ophthalmic infections in children presenting to Angkor Hospital for Children,
      Siem Reap, Cambodia.
AB  - BACKGROUND: Ophthalmic infections cause significant morbidity in Cambodian
      children but aetiologic data are scarce. We investigated the causes of acute eye
      infections in 54 children presenting to the ophthalmology clinic at Angkor
      Hospital for Children, Siem Reap between March and October 2012. FINDINGS: The
      median age at presentation was 3.6 years (range 6 days - 16.0 years). Forty two
      patients (77.8%) were classified as having an external eye infection, ten (18.5%)
      as ophthalmia neonatorum, and two (3.7%) as intra-ocular infection. Organisms
      were identified in all ophthalmia neonatorum patients and 85.7% of patients with
      an external eye infection. Pathogens were not detected in either of the intra
      ocular infection patients. Most commonly isolated bacteria were Staphylococcus
      aureus (23 isolates), coagulase-negative staphylococci (13), coliforms (7),
      Haemophilus influenzae/parainfluenzae (6), Streptococcus pneumoniae (4), and
      Neisseria gonorrhoeae (2). Chlamydia trachomatis DNA was detected in 60% of swabs
      taken from ophthalmia neonatorum cases. CONCLUSIONS: This small study
      demonstrates the wide range of pathogens associated with common eye infections in
      Cambodian children. The inclusion of molecular assays improved the spectrum of
      detectable pathogens, most notably in neonates.

PMID- 25369775
TI  - Generation and screening of oxime libraries addressing the neuronal GABA
      transporter GAT1.
AB  - The objective of the present study was to transfer the concept of library
      screening by MS binding assays, so far applied to pseudostatic hydrazine
      libraries, to static oxime libraries to screen for new potent inhibitors of
      mGAT1, the most abundant GABA transporter in the central nervous system that
      represents a validated drug target for the treatment of epilepsy. Library
      generation was performed by reaction of guvacine derivatives possessing a
      hydroxylamine functionality with various sets of four aldehydes. After dilution,
      the libraries were screened by competitive MS binding assays. Deconvolution
      experiments allowed hits in the most active libraries to be identified, and they
      were resynthesized for biological evaluation. That way a series of compounds was
      identified that displayed binding affinities >=8.00 (pKi ) at mGAT1, one of which
      was found to be the most potent mGAT1 inhibitor known to date in a functional
      GABA uptake assay with a pIC50 value of 8.27 +/- 0.03.

PMID- 25369776
TI  - K2p channels in plants and animals.
AB  - Two-pore domain potassium (K2P) channels are membrane proteins widely identified
      in mammals, plants, and other organisms. A functional channel is a dimer with
      each subunit comprising two pore-forming loops and four transmembrane domains.
      The genome of the model plant Arabidopsis thaliana harbors five genes coding for
      K2P channels. Homologs of Arabidopsis K2P channels have been found in all higher
      plants sequenced so far. As with the K2P channels in mammals, plant K2P channels
      are targets of external and internal stimuli, which fine-tune the electrical
      properties of the membrane for specialized transport and/or signaling tasks.
      Plant K2P channels are modulated by signaling molecules such as intracellular
      H(+) and calcium and physical factors like temperature and pressure. In this
      review, we ask the following: What are the similarities and differences between
      K2P channels in plants and animals in terms of their physiology? What is the
      nature of the last common ancestor (LCA) of these two groups of proteins? To
      answer these questions, we present physiological, structural, and phylogenetic
      evidence that discards the hypothesis proposing that the duplication and fusion
      that gave rise to the K2P channels occurred in a prokaryote LCA. Conversely, we
      argue that the K2P LCA was most likely a eukaryote organism. Consideration of
      plant and animal K2P channels in the same study is novel and likely to stimulate
      further exchange of ideas between students of these fields. 

PMID- 25369778
TI  - Update on Greenlight laser vaporization (PVP) 2014.
AB  - PURPOSE: To asses the (1) outcomes and (2) intraoperative, perioperative, and
      long-term complications of photoselective vaporization of the prostate (PVP) with
      Greenlight laser. METHODS: A systematic review of outcomes and complications of
      PVP was conducted. The article selection process was performed according to
      PRISMA guidelines and included publications published between 2009 and 2014.
      RESULTS: All generations of PVP (80, 120, 180 W) lead to a significant
      improvement of micturition symptoms (IPSS, QoL) and voiding parameters (Q max,
      PVR volume) during follow-up. Data on sexual function are heterogeneous and
      suggest a trend toward decline in erectile function in men with sustained
      preoperative erection. The rate of intraoperative complications is low. Data on
      peri- and postoperative complications show a large variation that mainly can be
      attributed to heterogeneity in documentation. CONCLUSIONS: PVP leads to a
      statistically significant and clinically relevant improvement of voiding
      parameters and micturition symptoms in patients with prostates <100 ml. The
      technique is characterized by a high degree of intra- and perioperative safety.
      Long-term evidence on functional outcomes and complications beyond 3 years from
      RCTs is currently missing for all generations of the Greenlight laser.

PMID- 25369777
TI  - Perturbation of chemical coupling by an endothelial Cx40 mutant attenuates
      endothelium-dependent vasodilation by KCa channels and elevates blood pressure in
      mice.
AB  - Mutant forms of connexin40 (Cx40) exist in the human population and predispose
      carriers to atrial fibrillation. Since endothelial expression of Cx40 is
      important for electrical and chemical communication within the arterial wall,
      carriers of mutant Cx40 proteins may be predisposed to peripheral arterial
      dysfunction and dysregulation of blood pressure. We have therefore studied mice
      expressing either a chemically dysfunctional mutant, Cx40T202S, or wild-type
      Cx40, with native Cx40, specifically in the endothelium. Blood pressure was
      measured by telemetry under normal conditions and during cardiovascular stress
      induced by locomotor activity, phenylephrine or nitric oxide blockade (N(omega)
      nitro-L-arginine methyl ester hydroxide, L-NAME). Blood pressure of Cx40T202STg
      mice was significantly elevated at night when compared with wild-type or Cx40Tg
      mice, without change in mean heart rate, pulse pressure or locomotor activity.
      Analysis over 24 h showed that blood pressure of Cx40T202STg mice was
      significantly elevated at rest and additionally during locomotor activity. In
      contrast, neither plasma renin concentration nor pressor responses to
      phenylephrine or L-NAME were altered, the latter indicating that nitric oxide
      bioavailability was normal. In isolated, pressurised mesenteric arteries,
      hyperpolarisation and vasodilation evoked by SKA-31, the selective modulator of
      SKCa and IKCa channels, was significantly reduced in Cx40T202STg mice, due to
      attenuation of the SKCa component. Acetylcholine-induced ascending vasodilation
      in vivo was also significantly attenuated in cremaster muscle arterioles of
      Cx40T202STg mice, compared to wild-type and Cx40Tg mice. We conclude that
      endothelial expression of the chemically dysfunctional Cx40T202S reduces
      peripheral vasodilator capacity mediated by SKCa-dependent hyperpolarisation and
      also increases blood pressure. 

PMID- 25369779
TI  - Symmetrically periodic segregation in a vertically vibrated binary granular bed.
AB  - Periodic segregation behaviors in fine mixtures of copper and alumina particles,
      including both percolation and eruption stages, are experimentally investigated
      by varying the ambient air pressure and vibrational acceleration. For the cases
      with moderate air pressure, the heaping profile of the granular bed keeps
      symmetrical in the whole periodic segregation. The symmetrical shape of the upper
      surface of the granular bed in the eruption stage, which resembles a miniature
      volcanic eruption, could be described by the Mogi model that illuminates the
      genuine volcanic eruption in the geography. When the air pressure increases, an
      asymmetrical heaping profile is observed in the eruption stage of periodic
      segregation. With using the image processing technique, we estimate a relative
      height difference between the copper and the alumina particles as the order
      parameter to quantitatively characterize the evolution of periodic segregation.
      Both eruption and percolation time, extracted from the order parameter, are
      plotted as a function of the vibration strength. Finally, we briefly discuss the
      air effect on the granular segregation behaviors. 

PMID- 25369780
TI  - Oscillatory potentials in electroretinogram as an early marker of visual
      abnormalities in vitamin A deficiency.
AB  - Vitamin A deficiency (VAD) caused by malnutrition and certain intestinal diseases
      induces visual impairments, including night blindness and photoreceptor cell
      dysfunction as indicated by reduced a- and b-waves in an electroretinogram (ERG).
      The effects of VAD on the inner retinal layer cells, including amacrine and
      ganglion cells, remain to be elucidated. The functions of these cells are
      reflected in oscillatory potentials (OPs), another component of the ERG. The
      present study investigated inner retinal layer cell function in VAD rats by
      analyzing OPs. In the present study, VAD was induced by feeding Brown Norway rats
      a vitamin A deficient diet for 10 weeks. A reduced body weight and peri-papillary
      opacification indicative of papilledema without histopathological alterations
      were observed, which are considered early symptoms of VAD. At this stage, the ERG
      revealed reduced OPs as well as a- and b-waves at various intensities of light
      stimulation. Further analysis indicated that the ratio of the alterations in OPs
      was more significant than those of a- and b-waves. After 5 weeks of recovery,
      these changes returned to control levels. These results suggest that OPs are the
      most sensitive and early marker of VAD-associated visual impairment in the ERG.

PMID- 25369781
TI  - DNA repair in diffuse large B-cell lymphoma: a molecular portrait.

PMID- 25369782
TI  - A microwave synthesis of mesoporous NiCo2O4 nanosheets as electrode materials for
      lithium-ion batteries and supercapacitors.
AB  - A facile microwave method was employed to synthesize NiCo2 O4 nanosheets as
      electrode materials for lithium-ion batteries and supercapacitors. The structure
      and morphology of the materials were characterized by X-ray diffraction, field
      emission scanning electron microscopy, transmission electron microscopy and
      Brunauer-Emmett-Teller methods. Owing to the porous nanosheet structure, the
      NiCo2 O4 electrodes exhibited a high reversible capacity of 891 mA h g(-1) at a
      current density of 100 mA g(-1) , good rate capability and stable cycling
      performance. When used as electrode materials for supercapacitors, NiCo2 O4
      nanosheets demonstrated a specific capacitance of 400 F g(-1) at a current
      density of 20 A g(-1) and superior cycling stability over 5000 cycles. The
      excellent electrochemical performance could be ascribed to the thin porous
      structure of the nanosheets, which provides a high specific surface area to
      increase the electrode-electrolyte contact area and facilitate rapid ion
      transport. 

PMID- 25369783
TI  - Leveraging birth defects surveillance data for health services research.

PMID- 25369784
TI  - Downregulation of PLZF in human hepatocellular carcinoma and its clinical
      significance.
AB  - Promyelocytic leukemia zinc finger (PLZF) acts as a tumor-suppressor gene in a
      series of cancers including prostate, melanoma, colon cancer and leukemia.
      However, its role in hepatocellular carcinoma (HCC) has not yet been illustrated.
      The present study aimed to investigate the expression and epigenetic regulation
      of PLZF as well as its clinical significance in HCC. We found that the expression
      of PLZF was significantly downregulated in HCC samples at both the RNA level
      (P<0.001) and protein level compared with these levels in adjacent normal
      tissues. The relative expression level of PLZF was also positively correlated
      with the ALP level (P=0.026) noted in the HCC patients. However, hypermethylation
      was only detected in one out of 5 paired HCC samples, indicating that methylation
      of the selected promoter region (from -1702 to -1388) may not be the major
      regulatory mechanism for the downregulation of PLZF in HCC. A receiver operating
      characteristic (ROC) curve was created to evaluate the diagnostic value for
      differentiating between HCC and benign diseases. The area under the ROC curve
      (AUC) for indicating the value of PLZF as an HCC biomarker was 0.794 (95% CI,
      0.697-0.892; P<0.001). Taken together, our results suggest that PLZF may play an
      important role in HCC development and may be a potential biomarker for the
      diagnosis of HCC.

PMID- 25369786
TI  - Structural and mechanical properties of cardiolipin lipid bilayers determined
      using neutron spin echo, small angle neutron and X-ray scattering, and molecular
      dynamics simulations.
AB  - The detailed structural and mechanical properties of a tetraoleoyl cardiolipin
      (TOCL) bilayer were determined using neutron spin echo (NSE) spectroscopy, small
      angle neutron and X-ray scattering (SANS and SAXS, respectively), and molecular
      dynamics (MD) simulations. We used MD simulations to develop a scattering density
      profile (SDP) model, which was then utilized to jointly refine SANS and SAXS
      data. In addition to commonly reported lipid bilayer structural parameters,
      component distributions were obtained, including the volume probability, electron
      density and neutron scattering length density. Of note, the distance between
      electron density maxima DHH (39.4 A) and the hydrocarbon chain thickness 2DC
      (29.1 A) of TOCL bilayers were both found to be larger than the corresponding
      values for dioleoyl phosphatidylcholine (DOPC) bilayers. Conversely, TOCL
      bilayers have a smaller overall bilayer thickness DB (36.7 A), primarily due to
      their smaller headgroup volume per phosphate. SDP analysis yielded a lipid area
      of 129.8 A(2), indicating that the cross-sectional area per oleoyl chain in TOCL
      bilayers (i.e., 32.5 A(2)) is smaller than that for DOPC bilayers. Multiple sets
      of MD simulations were performed with the lipid area constrained at different
      values. The calculated surface tension versus lipid area resulted in a lateral
      area compressibility modulus KA of 342 mN m(-1), which is slightly larger
      compared to DOPC bilayers. Model free comparison to experimental scattering data
      revealed the best simulated TOCL bilayer from which detailed molecular
      interactions were determined. Specifically, Na(+) cations were found to interact
      most strongly with the glycerol hydroxyl linkage, followed by the phosphate and
      backbone carbonyl oxygens. Inter- and intra-lipid interactions were facilitated
      by hydrogen bonding between the glycerol hydroxyl and phosphate oxygen, but not
      with the backbone carbonyl. Finally, analysis of the intermediate scattering
      functions from NSE spectroscopy measurements of TOCL bilayers yielded a bending
      modulus KC of 1.06 * 10(-19) J, which was larger than that observed in DOPC
      bilayers. Our results show the physicochemical properties of cardiolin bilayers
      that may be important in explaining their functionality in the inner
      mitochondrial membrane. 

PMID- 25369787
TI  - A co-operative Ni-Cu system for Csp-Csp and Csp-Csp(2) cross-coupling providing a
      direct access to unsymmetrical 1,3-diynes and en-ynes.
AB  - An efficient cross-coupling of alkynes with alkynyl and alkenyl halides catalysed
      by a Ni-Cu system without any ligand has been achieved. The reaction is suggested
      to proceed by Ni(0) catalysis assisted by Cu(I). A series of functionalised
      diaryl, aryl-alkyl, aryl-heteroaryl, diheteroaryl 1,3-di-ynes and en-ynes are
      obtained in high yields.

PMID- 25369785
TI  - Effector CD4 T-cell transition to memory requires late cognate interactions that
      induce autocrine IL-2.
AB  - It is unclear how CD4 T-cell memory formation is regulated following pathogen
      challenge, and when critical mechanisms act to determine effector T-cell fate.
      Here, we report that following influenza infection most effectors require signals
      from major histocompatibility complex class II molecules and CD70 during a late
      window well after initial priming to become memory. During this timeframe,
      effector cells must produce IL-2 or be exposed to high levels of paracrine or
      exogenously added IL-2 to survive an otherwise rapid default contraction phase.
      Late IL-2 promotes survival through acute downregulation of apoptotic pathways in
      effector T cells and by permanently upregulating their IL-7 receptor expression,
      enabling IL-7 to sustain them as memory T cells. This new paradigm defines a late
      checkpoint during the effector phase at which cognate interactions direct CD4 T
      cell memory generation. 

PMID- 25369788
TI  - Endoscopic upper airway evaluation in obstructive sleep apnea: Mueller's maneuver
      versus simulation of snoring.
AB  - PURPOSE: This study aimed to compare fiberoptic nasopharyngoscopy during
      Mueller's maneuver (FNMM) with fiberoptic nasopharyngoscopy with simulation of
      snoring (FNSS) for upper airway (UA) assessment in patients with obstructive
      sleep apnea and hypopnea syndrome. We also investigated the relationship between
      daytime endoscopic examinations and nocturnal pressure measurements. METHODS: We
      conducted a prospective, case-series study at Peking Union Medical College
      Hospital. All patients were evaluated by daytime FNMM and FNSS. The retropalatal
      and retroglossal regions were continuously video recorded during quiet breathing,
      FNMM, and FNSS. We calculated the narrowing rate and determined the level of
      obstruction and pattern of collapse (lateral, anterior-posterior, or concentric).
      Patients also underwent nocturnal pressure measurements to identify obstruction
      sites. RESULTS: Ninety-two patients were enrolled. FNMM and FNSS detected
      retropalatal obstruction in every case. Fifty-six and 38 patients had
      retroglossal obstruction detected by FNMM and FNSS, respectively. There was
      diagnostic agreement between FNMM and FNSS in 72 patients when diagnosing
      retroglossal obstruction, but the patterns of collapse were different using each
      technique. Pressure measurements showed that lower apnea and hypopnea index (AHI)
      and the proportion of lower AHI were significantly lower in the isolated
      retropalatal obstruction group than in the combined obstruction group diagnosed
      with either FNMM or FNSS (p < 0.01). CONCLUSIONS: Daytime FNMM and FNSS are
      reliable for evaluating the level of obstruction and pattern of UA collapse, and
      correlate with sleep study findings. FNSS may provide some different information
      regarding patterns of collapse and retroglossal obstruction from FNMM. Both
      techniques are helpful for determining surgical strategies.

PMID- 25369789
TI  - Predictors of successful completion of diagnostic home sleep testing in patients
      with chronic kidney disease.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is common among patients with chronic
      kidney disease (CKD) and end-stage renal disease (ESRD). Home sleep testing is
      used to diagnose OSA in many studies investigating sleep-disordered breathing in
      this population. However, failure to successfully complete the test is a
      significant source of participant exclusion from research studies and delayed
      diagnosis in clinical practice. The objective of the study was to identify
      potential factors impeding acceptance and successful completion of home sleep
      testing in patients with kidney disease. METHODS: Four hundred and nineteen
      patients were recruited from nephrology clinics and dialysis units. Following
      completion of a sleep and medical history questionnaire, all patients were
      invited to perform a single night, home sleep study. Acceptance or refusal of the
      test was noted, as well as the success of the sleep study, as determined by a
      review of the raw data by a sleep medicine physician. RESULTS: Male gender (OR =
      1.61, CI = 1.02-2.53), hypertension (OR = 2.01, CI = 1.17-3.45), and snoring (OR
      = 1.75, CI = 1.11-2.77) were associated with sleep test acceptance. Older
      patients were less likely to accept the test (OR = 0.48, CI = 0.30-0.76).
      Diabetics were less likely to complete the sleep test successfully (OR = 0.28, CI
      = 0.12-0.66). CONCLUSIONS: Advanced age is an important factor in test refusal
      and complications of diabetes contributes to test failure. Symptom matching may
      be a source of selection bias, as patients with risk factors for OSA are more
      likely to accept the diagnostic test.

PMID- 25369790
TI  - Contemporary assessment of the prevalence of smell and taste problems in adults.
AB  - OBJECTIVES/HYPOTHESIS: Determine the prevalence of smell disturbance and taste
      disturbance and associated factors in adults. STUDY DESIGN: Cross-sectional
      analysis of nationwide household health survey. METHODS: Data from the taste and
      smell disorders component of the National Health and Nutrition Examination Survey
      (NHANES) 2011 to 2012 were examined. The prevalence of self-reported problems
      with taste and/or smell among adults and the associated symptom frequency,
      related healthcare provider interactions, and symptoms/etiologies (e.g.,
      persistent cold/flu, dry mouth, or head injury, etc.) were determined.
      Associations between sex and age with smell and taste disturbances as well as the
      relationship between smell and taste disturbances were determined. RESULTS: Among
      142.5 +/- 12.6 million adult Americans (raw N = 3,594), there were an estimated
      15.1 +/- 2.1 million individuals (10.6% +/- 1.0%) with self-reported smell
      disturbance in the prior 12 months. Sex was not associated with the prevalence of
      self-reported smell disturbance (P = 0.146), but increasing age was associated
      with an increasing prevalence of smell disturbance (odds ratio [OR] 1.147; 95%
      confidence interval [CI], 1.003-1.312). An estimated 7.5 +/- 0.6 million
      individuals (5.3% +/- 0.3%) reporting a problem with taste in the prior 12
      months. Sex was not associated with the prevalence of taste disturbance (P =
      0.947) but increasing age was (OR 1.202; 1.037-1.395). Among 19.4 +/- 2.2 million
      reporting smell and/or taste abnormality, 20.2% +/- 2.3% discussed this with a
      healthcare provider and 5.8% +/- 1.4% felt it interfered with their daily life.
      CONCLUSION: A significant number of adult Americans report problems with smell
      disturbance and taste disturbance. Further work to identify patients whose smell
      or taste disturbance can be helped is warranted. LEVEL OF EVIDENCE: 2b.

PMID- 25369792
TI  - Diversity-oriented synthesis of intensively blue emissive 3-hydroxyisoquinolines
      by sequential Ugi four-component reaction/reductive Heck cyclization.
AB  - A convergent approach to highly functionalized 3-hydroxyisoquinolines is
      reported. The key steps are an Ugi multicomponent reaction and a subsequent
      intramolecular reductive Heck reaction; these can also be performed as a one-pot
      procedure. The structures display very interesting properties as blue
      fluorescence emitters. Photophysical studies on the absorption and static
      fluorescence indicate that the substitution pattern on the pyridyl part
      influences the optical properties only to a minor extent, unless the amide
      substituent becomes sterically demanding and leads to significant nonradiative
      deactivation. The donor substitution on the benzo core considerably enhances the
      fluorescence quantum yields and trimethoxy substitution causes a pronounced
      redshift of the emission bands. Protonation of the isoquinolyl nitrogen atom
      causes efficient static quenching of the fluorescence. 

PMID- 25369791
TI  - The feasibility and acceptability of the provision of alcohol screening and brief
      advice in pharmacies for women accessing emergency contraception: an evaluation
      study.
AB  - BACKGROUND: It is widely accepted that excessive drinking contributes to both
      health and social problems. There has been considerable interest in the potential
      of community pharmacies as a setting for health advice, and evidence suggests
      that interventions by pharmacists can be effective. Research on interventions
      relating to alcohol consumption in primary care has focused on general practice,
      and although some evidence exists about the efficacy of pharmacy interventions,
      little research to date has taken place in the UK. The aim of this study was to
      evaluate the acceptability of alcohol screening and brief interventions to women
      accessing emergency hormonal contraception (EHC) in community pharmacies.
      METHODS: An initiative whereby women who accessed community pharmacies for EHC
      would be asked to complete an AUDIT questionnaire following their EHC
      consultation was introduced by a Primary Care Trust (PCT) in the North-East of
      England. The evaluation incorporated three strands: interviewing pharmacists (n =
      14) about the implementation and acceptability of the initiative; interviewing
      clients (n = 22) identified as "low risk" to understand their perceptions of the
      initiative; conducting online follow-up surveys with clients in the "risky" group
      (n = 53) to evaluate the impact of the initiative on their alcohol consumption
      and contraceptive behaviour, as well as their perceptions of the service.
      RESULTS: Pharmacists' attitudes towards screening were generally positive,
      although there were organisational obstacles to providing the service. Some felt
      uncertain about engaging clients in conversation about a sensitive topic.
      However, clients themselves did not report feeling embarrassed or upset, and most
      were happy to talk to the pharmacist and be given advice. Most clients felt that
      the pharmacist was an appropriate person to carry out alcohol screening and
      advice. CONCLUSIONS: It is feasible for pharmacists to carry out screening and
      brief advice, and most customers find it acceptable. However, pharmacist take-up
      of the service and participation in the study was low. Pharmacists were
      enthusiastic about providing screening and other health promotion services;
      targeting different population groups for alcohol screening may be more
      successful. Delivery of the AUDIT tool by pharmacists may not obtain reliable
      responses from some specific client groups.

PMID- 25369793
TI  - Factors relating to consent for organ donation: prospective data on potential
      organ donors.
AB  - BACKGROUND: Obtaining family consent to organ donation is a significant obstacle
      to improving further Australian deceased organ donation rates. Currently, neither
      the consent rates for donors eligible to donate after circulatory death, nor
      factors that influence decision to decline or consent to donation in general are
      known in Australia. METHODS: This study at four university teaching hospitals in
      Melbourne, Victoria, examined consecutive patients where organ donation was
      discussed with the family RESULTS: A total of 123 cases were identified; the
      family consent rate was 52.8%, and 34.1% proceeded to donation. Consent to
      donation was related to potential donor factors such as country of birth,
      cultural background in Australia, a non-religious or Christian background and
      registration on the Australian Organ Donor Register. Family-related factors
      included being English speaking and having knowledge of the deceased's wishes
      about organ donation. Family of donation after circulatory death-eligible donors
      were less likely to consent to donation than the family of donation after brain
      death-eligible donors, although not reaching statistical significance. Among
      consented potential donors, those eligible for donation after brain death and
      with a shorter length of stay were more likely to proceed to donating organs for
      transplantation. CONCLUSION: Despite a small sample size, these findings describe
      current consent and donation rates and associated factors and may assist in
      improving conversations about organ donation.

PMID- 25369794
TI  - Confidence in government and vaccination willingness in the USA.
AB  - The most recent internationally widespread disease outbreak occurred during the
      flu season of 2009 and 2010. On April 2009, the first cases of influenza A (H1N1)
      (Popularly called, Swine Flu) were confirmed in the USA and UK following a novel
      virus that was first identified in Mexico. As the virus spread rapidly, the risk
      of morbidity and mortality increased in several countries. In this paper, we rely
      on the social cognitive theory of risk to assess the willingness of the US public
      to comply with vaccination and reduce the risk of sickness and death from the
      flu. We conduct a secondary data analysis of the Pew Research for the People and
      Press October 2009 and investigate the factors associated with willingness to
      take the swine flu vaccine (n = 1000). The findings indicate that the decision to
      take the swine flu vaccination was highly polarized across partisan lines.
      Controlling for education, income and demographic factors, the likelihood of
      taking the vaccine was associated with party identification. Individuals that
      identified themselves as Democrats were more likely to be willing to take the
      swine vaccine than individuals that identify themselves as Republicans and
      Independents. Confidence in the ability of the government to deal with the swine
      flu crisis seems to explain party identification differences in the willingness
      to take the vaccine. The implications of the findings are discussed.

PMID- 25369795
TI  - RNA-seq profiling of a radiation resistant and radiation sensitive prostate
      cancer cell line highlights opposing regulation of DNA repair and targets for
      radiosensitization.
AB  - BACKGROUND: Radiotherapy is a chosen treatment option for prostate cancer
      patients and while some tumours respond well, up to 50% of patients may
      experience tumour recurrence. Identification of functionally relevant predictive
      biomarkers for radioresponse in prostate cancer would enable radioresistant
      patients to be directed to more appropriate treatment options, avoiding the side
      effects of radiotherapy. METHODS: Using an in vitro model to screen for novel
      biomarkers of radioresistance, transcriptome analysis of a radioresistant (PC-3)
      and radiosensitive (LNCaP) prostate cancer cell line was performed. Following
      pathway analysis candidate genes were validated using qRT-PCR. The DNA repair
      pathway in radioresistant PC-3 cells was then targeted for radiation
      sensitization using the PARP inhibitor, niacinimide. RESULTS: Opposing regulation
      of a DNA repair and replication pathway was observed between PC-3 and LNCaP cells
      from RNA-seq analysis. Candidate genes BRCA1, RAD51, FANCG, MCM7, CDC6 and ORC1
      were identified as being significantly differentially regulated post-irradiation.
      qRT-PCR validation confirmed BRCA1, RAD51 and FANCG as being significantly
      differentially regulated at 24 hours post radiotherapy (p-value =0.003, 0.045 and
      0.003 respectively). While the radiosensitive LNCaP cells down-regulated BRCA1,
      FANCG and RAD51, the radioresistant PC-3 cell line up-regulated these candidates
      to promote cell survival post-radiotherapy and a similar trend was observed for
      MCM7, CDC6 and ORC1. Inhibition of DNA repair using niacinamide sensitised the
      radioresistant cells to irradiation, reducing cell survival at 2 Gy from 66% to
      44.3% (p-value =0.02). CONCLUSIONS: These findings suggest that the DNA repair
      candidates identified via RNA-seq hold potential as both targets for radiation
      sensitization and predictive biomarkers in prostate cancer.

PMID- 25369796
TI  - Variation of community consultation and public disclosure for a pediatric multi
      centered "Exception from Informed Consent" trial.
AB  - BACKGROUND: The US federal regulation "Exception from Informed Consent for
      Emergency Research," 21 Code of Federal Regulations 50.24, permits emergency
      research without informed consent under limited conditions. Additional safeguards
      to protect human subjects include requirements for community consultation and
      public disclosure prior to starting the research. Because the regulations are
      vague about these requirements, Institutional Review Boards determine the
      adequacy of these activities at a local level. Thus, there is potential for broad
      interpretation and practice variation. AIM: To describe the variation of
      community consultation and public disclosure activities approved by Institutional
      Review Boards, and the effectiveness of this process for a multi-center,
      Exception from Informed Consent, pediatric status epilepticus clinical research
      trial. METHODS: Community consultation and public disclosure activities were
      analyzed for each of the 15 participating sites. Surveys were conducted with
      participants enrolled in the status epilepticus trial to assess the effectiveness
      of public disclosure dissemination prior to study enrollment. RESULTS: Every
      Institutional Review Board, among the 15 participating sites, had a varied
      interpretation of Exception from Informed Consent regulations for community
      consultation and public disclosure activities. Institutional Review Boards
      required various combinations of focus groups, interviews, surveys, and meetings
      for community consultation, and news releases, mailings, and public service
      announcements for public disclosure. At least 4335 patients received information
      about the study from these efforts. In all, 158 chose to be included in the "Opt
      Out" list. Of the 304 participants who were enrolled under Exception from
      Informed Consent, 12 (5%) had heard about the study through community
      consultation or public disclosure activities. The activities reaching the highest
      number of participants were surveys and focus groups associated with existing
      meetings. Public disclosure activities were more efficient and cost-effective if
      they were part of an in-hospital resource for patients and families. CONCLUSION:
      There is substantial variation in Institutional Review Boards' interpretations of
      the federal regulations for community consultation and public disclosure. One of
      the goals of community consultation and public disclosure efforts for emergency
      research is to provide community members an opportunity to opt out of Exception
      from Informed Consent research; however, rarely do patients or their legally
      authorized representatives report having learned about a study prior to
      enrollment.

PMID- 25369797
TI  - Brazilin Isolated from Caesalpinia sappan suppresses nuclear envelope reassembly
      by inhibiting barrier-to-autointegration factor phosphorylation.
AB  - To date, many anticancer drugs have been developed by directly or indirectly
      targeting microtubules, which are involved in cell division. Although this
      approach has yielded many anticancer drugs, these drugs produce undesirable side
      effects. An alternative strategy is needed, and targeting mitotic exit may be one
      alternative approach. Localization of phosphorylated barrier-to-autointegration
      factor (BAF) to the chromosomal core region is essential for nuclear envelope
      compartment relocalization. In this study, we isolated brazilin from Caesalpinia
      sappan Leguminosae and demonstrated that it inhibited BAF phosphorylation in
      vitro and in vivo. Moreover, we demonstrated direct binding between brazilin and
      BAF. The inhibition of BAF phosphorylation induced abnormal nuclear envelope
      reassembly and cell death, indicating that perturbation of nuclear envelope
      reassembly could be a novel approach to anticancer therapy. We propose that
      brazilin isolated from C. sappan may be a new anticancer drug candidate that
      induces cell death by inhibiting vaccinia-related kinase 1-mediated BAF
      phosphorylation. 

PMID- 25369799
TI  - Active food packaging based on molecularly imprinted polymers: study of the
      release kinetics of ferulic acid.
AB  - A novel active packaging based on molecularly imprinted polymer (MIP) was
      developed for the controlled release of ferulic acid. The release kinetics of
      ferulic acid from the active system to food simulants (10, 20, and 50% ethanol
      (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v)
      and isooctane), and real food samples at different temperatures were studied. The
      key parameters of the diffusion process were calculated by using a mathematical
      modeling based on Fick's second law. The ferulic acid release was affected by the
      temperature as well as the percentage of ethanol of the simulant. The fastest
      release occurred in 95% ethanol (v/v) at 20  degrees C. The diffusion
      coefficients (D) obtained ranged between 1.8 * 10(-11) and 4.2 * 10(-9) cm(2)/s.
      A very good correlation between experimental and estimated data was obtained, and
      consequently the model could be used to predict the release of ferulic acid into
      food simulants and real food samples. 

PMID- 25369798
TI  - Incidence and risk of severe infections associated with anti-epidermal growth
      factor receptor monoclonal antibodies in cancer patients: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Anti-epidermal growth factor receptor (EGFR)-monoclonal antibodies
      (MoAbs) have been widely used in a variety of malignancies. Severe infections
      (>=grade 3) are potentially life-threatening adverse events with these drugs.
      However, the contribution of anti-EGFR MoAbs to infections is still unknown. We
      performed this meta-analysis to determine the overall incidence and risk of
      severe infections in cancer patients treated with these drugs. METHODS: The
      databases of PubMed and abstracts presented at oncology conferences and published
      in the proceedings were searched for relevant studies from January 2000 to May
      2014. Summary incidences, relative risks (RRs) and 95% confidence intervals (CIs)
      were calculated by using either random effects or fixed effect models according
      to the heterogeneity of included studies. RESULTS: A total of 14,066 patients
      from 26 randomized controlled trials (RCTs) were included. The use of anti-EGFR
      MoAbs significantly increased the risk of developing severe infections (RR 1.34,
      95%CI: 1.10 to 1.62, P=0.003) in cancer patients, but not for fatal infections
      (RR 1.62, 95%CI: 0.81 to 3.26, P=0.18). Meta-regression indicated the infections
      might possibly occur early in the treatment with anti-EGFR MoAbs. On sub-group
      analysis, the risk of severe infections significantly varied with tumor type
      (P=0.001). When stratified by specific anti-EGFR MoAbs, a significantly increased
      risk of infections with cetuximab was observed (P<0.001), but not for panitumumab
      (P=0.98). Additionally, the use of anti-EGFR MoAbs significantly increased the
      risk of severe infections when used in conjunction with cisplatin (RR 1.48, 95%CI
      1.22 to 1.79, P<0.001) or irinotecan (RR 1.53, 95%CI 1.12 to 2.10, P=0.008). When
      stratified by specific infectious events, anti-EGFR-MoAbs significantly increased
      the risk of developing severe sepsis (RR 4.30, 95%CI: 1.80 to 10.27; P=0.001).
      CONCLUSIONS: Anti-EGFR MoAbs treatment significantly increases the risk of
      developing severe infectious events in cancer patients. The risk may vary with
      tumor types. Clinicians should be aware of the risks of severe infections with
      the administration of these drugs in cancer patients.

PMID- 25369800
TI  - Alignment and structural control of nitrogen-doped carbon nanotubes by utilizing
      precursor concentration effect.
AB  - Nitrogen-doped carbon nanotubes (NCNTs) were prepared using a simple ultrasonic
      spray pyrolysis method. The precursor concentration effect was examined to
      effectively control alignment, open tip and diameter of the NCNTs by changing
      xylene/cyclohexylamine ratio. The structure and morphology of the resultant NCNTs
      were characterized by scanning electron microscopy, transmission electron
      microscopy and x-ray photoelectron spectroscopy. The degree of alignment and the
      diameter of the NCNTs increased as the xylene/cyclohexylamine precursor mixture
      was changed from 0 to 35% cyclohexylamine. This precursor composition also caused
      a large number of open-ended nanotubes to form with graphite layers inside the
      cavities of the NCNTs. However, further increase cyclohexylamine content in the
      precursor reduced the degree of alignment and diameter of the NCNTs. We
      demonstrate control over the NCNT alignment and diameter, along with the
      formation of open-ended nanotube tips, and propose a growth mechanism to
      understand how these properties are interlinked. 

PMID- 25369801
TI  - Upregulated periostin promotes angiogenesis in keloids through activation of the
      ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression
      of VEGF and angiopoietin-1.
AB  - Periostin, a secreted extracellular matrix protein, is highly expressed in wound
      healing and in various types of human cancer and is involved in angiogenesis.
      Keloids, considered dermal benign tumors, are granulomatous lesions characterized
      by capillary proliferation. However, the underlying regulatory mechanism of
      angiogenesis in keloids remains to be elucidated. The present study aimed to
      examine the effect of periostin on angiogenesis in keloids. The expression of
      periostin was upregulated and the vessel density was higher in human keloids
      compared with normal tissue, observed following staining with CD31 and CD105.
      Periostin demonstrated a markedly positive correlation with blood vessel density,
      which was assessed using CD31 staining (r=0.711; P<0.01) and a weak correlation
      was observed using CD105 staining (r=0.251; P<0.01). Conditioned medium from
      keloid fibroblasts (KFs) promoted the migration and tube formation of human
      umbilical vein endothelial cells (HUVECs) compared with normal fibroblasts and
      this effect may have been abrogated by the short hairpin RNA knockdown of
      periostin. Treatment with recombinant human periostin promoted the migration and
      tube formation of HUVECs by activating the extracellular signal-regulated kinase
      1/2 and focal adhesion kinase signaling pathway. In addition, periostin increased
      the secretion of vascular endothelial growth factor and angiopoietin-1 in the
      KFs. In conclusion, these data suggested that upregulation in the level of
      periostin may promote angiogenesis directly and indirectly in keloids and may be
      a key factor in keloid development. Periostin may, therefore, be a promising
      therapeutic target in the treatment of keloids and other angioproliferative
      diseases.

PMID- 25369803
TI  - Potential proton beam therapy for recurrent endometrial cancer in the vagina.
AB  - Proton beam radiotherapy mainly has been used in the gynecological field in
      patients with cervical cancer. The efficacy of proton beam therapy in patients
      with recurrent endometrial cancer has not yet been determined. A 77-year-old
      endometrial cancer patient presented with recurrence in the vagina without
      distant metastasis following hysterectomy. A hard mass measuring 6 cm originated
      from the apex of the vagina, surrounded the vaginal cavity, and infiltrated the
      proximal and distal vagina. The patient received proton beam radiotherapy using a
      less invasive particle treatment system while minimizing the dose to the
      surrounding normal tissues. The dose to the planning target volume was 74 Gy
      (relative biological effectiveness) with 37 fractions. The patient was treated
      with 150-210-MeV proton beams for 53 days. Proton beam therapy led to the
      disappearance of tumors without any complications except for grade 1 cystitis
      although evidence of further complications is not available past our 6-month
      follow-up period. Proton beam therapy may become a useful treatment modality for
      recurrent endometrial cancer as well as cervical uterine cancer. 

PMID- 25369802
TI  - Clinical associations between IL-17 family cytokines and periodontitis and
      potential differential roles for IL-17A and IL-17E in periodontal immunity.
AB  - OBJECTIVE: IL-17A is implicated in periodontitis pathogenesis. The roles of IL
      17B-IL-17F and IL-17A/F are unknown. This study aimed to determine clinical
      associations between IL-17 family cytokines and periodontitis and to investigate
      the biological roles of IL-17A and IL-17E using in vitro model systems. MATERIALS
      AND METHODS: Samples from 97 patients with periodontitis and 77 healthy
      volunteers were used in the study. Serum, saliva and gingival crevicular fluid
      (GCF) levels of IL-17 family cytokines were measured by ELISA. Oral keratinocytes
      were stimulated with a P. gingivalis biofilm, or IL-17A, in the presence and
      absence of IL-17E and the expression of IL-8 and CXCL5 were investigated by ELISA
      and real-time-PCR. NF-kappaB phosphorylation in similar experiments was also
      measured using a cell-based ELISA. RESULTS: Serum, saliva and GCF IL-17A levels
      were higher in periodontitis patients and correlated positively with clinical
      parameters of attachment loss, pocket depth and bleeding on probing. Serum IL-17E
      levels were lower in periodontitis patients and the serum IL-17A:IL-17E ratio
      correlated positively with clinical parameters. In vitro, IL-17E inhibited
      Porphyromonas gingivalis and IL-17A induced expression of chemokines by reducing
      phosphorylation of the NF-kappaB p65 subunit. CONCLUSIONS: Serum IL-17A:IL-17E
      may be a marker of disease severity. IL-17E may have opposing roles to IL-17A in
      periodontitis pathogenesis. IL-17E can negatively regulate IL-17A and periodontal
      pathogen induced expression of chemokines by oral keratinocytes.

PMID- 25369804
TI  - Renal dysfunction is associated with a reduced contribution of nitric oxide and
      enhanced vasoconstriction after a congenital renal mass reduction in sheep.
AB  - BACKGROUND: Children born with reduced congenital renal mass have an increased
      risk of hypertension and chronic kidney disease in adulthood, although the
      mechanisms are poorly understood. Similar sequelae occur after fetal
      uninephrectomy (uni-x) in sheep, leading to a 30% nephron deficit. We
      hypothesized that renal dysfunction is underpinned by a reduced contribution of
      nitric oxide (NO) and vascular dysfunction in uni-x sheep. METHODS AND RESULTS:
      In 5-year-old female uni-x and sham sheep, mean arterial pressure, glomerular
      filtration rate, and renal blood flow were measured before and during NO
      inhibition (N(omega)-nitro-l-arginine methyl ester [L-NAME]). Reactivity was
      assessed in resistance arteries, including renal lobar and arcuate arteries.
      Basal mean arterial pressure was 15 mm Hg higher and glomerular filtration rate
      and renal blood flow were ~30% lower (P<0.001) in uni-x animals. L-NAME increased
      mean arterial pressure by ~17 mm Hg in both groups, whereas glomerular filtration
      rate and renal blood flow were decreased less in uni-x sheep (PInteraction<0.01).
      Endothelial NO synthase and Ser-1177-phosphorylated endothelial NO synthase
      protein levels were upregulated in renal cortex of uni-x sheep (P<0.05). Lobar
      arteries of uni-x sheep had enhanced responsiveness to phenylephrine and
      nitrotyrosine staining and reduced sensitivity to endothelial stimulation.
      Vasodilator prostanoid contribution to endothelium-dependent relaxation was
      reduced in lobar arteries of uni-x sheep, accompanied by reduced cyclooxygenase-1
      and -2 gene expression (P<0.05). Neurovascular constriction was enhanced ~1.5
      fold in renal arteries of uni-x sheep (P<0.05). CONCLUSIONS: Renal dysfunction
      after congenital renal mass reduction is associated with impaired regulation of
      renal hemodynamics by NO. Reductions in renal blood flow and glomerular
      filtration rate are underpinned by impaired basal NO contribution, endothelial
      dysfunction, and enhanced vascular responsiveness to sympathetic nerve
      stimulation.

PMID- 25369805
TI  - Carabin protects against cardiac hypertrophy by blocking calcineurin, Ras, and
      Ca2+/calmodulin-dependent protein kinase II signaling.
AB  - BACKGROUND: Cardiac hypertrophy is an early hallmark during the clinical course
      of heart failure and is regulated by various signaling pathways. However, the
      molecular mechanisms that negatively regulate these signal transduction pathways
      remain poorly understood. METHODS AND RESULTS: Here, we characterized Carabin, a
      protein expressed in cardiomyocytes that was downregulated in cardiac hypertrophy
      and human heart failure. Four weeks after transverse aortic constriction, Carabin
      deficient (Carabin(-/-)) mice developed exaggerated cardiac hypertrophy and
      displayed a strong decrease in fractional shortening (14.6+/-1.6% versus 27.6+/
      1.4% in wild type plus transverse aortic constriction mice; P<0.0001).
      Conversely, compensation of Carabin loss through a cardiotropic adeno-associated
      viral vector encoding Carabin prevented transverse aortic constriction-induced
      cardiac hypertrophy with preserved fractional shortening (39.9+/-1.2% versus
      25.9+/-2.6% in control plus transverse aortic constriction mice; P<0.0001).
      Carabin also conferred protection against adrenergic receptor-induced hypertrophy
      in isolated cardiomyocytes. Mechanistically, Carabin carries out a tripartite
      suppressive function. Indeed, Carabin, through its calcineurin-interacting site
      and Ras/Rab GTPase-activating protein domain, functions as an endogenous
      inhibitor of calcineurin and Ras/extracellular signal-regulated kinase
      prohypertrophic signaling. Moreover, Carabin reduced Ca(2+)/calmodulin-dependent
      protein kinase II activation and prevented nuclear export of histone deacetylase
      4 after adrenergic stimulation or myocardial pressure overload. Finally, we
      showed that Carabin Ras-GTPase-activating protein domain and calcineurin
      interacting domain were both involved in the antihypertrophic action of Carabin.
      CONCLUSIONS: Our study identifies Carabin as a negative regulator of key
      prohypertrophic signaling molecules, calcineurin, Ras, and Ca(2+)/calmodulin
      dependent protein kinase II and implicates Carabin in the development of cardiac
      hypertrophy and failure.

PMID- 25369806
TI  - Differentiation of Schwann-like cells from human umbilical cord blood mesenchymal
      stem cells in vitro.
AB  - The use of artificial nerves for the repair of peripheral nerve defects is
      restricted by the limited sources of Schwann cells (SCs). Human mesenchymal stem
      cell (MSC)-derived Schwann-like cells are considered an alternative and desirable
      cell source. The aim of the present study was to establish a method of inducing
      directional differentiation of human umbilical cord blood (hUCB) MSCs into
      Schwann-like cells. Cells isolated from hUCB were cultured in MesenCult complete
      medium, a specialized culture medium for MSCs, to expand hUCBMSCs. hUCBMSCs were
      purified by repeated changing of the medium, and they were identified by
      detection of the specific cell surface markers for MSCs. For differentiation of
      Schwann-like cells from hUCBMSCs, the purified cells were sequentially cultured
      in DMEM/F12 medium with various additives. Differentiated Schwann-like cells were
      identified by the detection of SC-specific markers, including S100b, glial
      fibrillary acidic protein and P75, by immunocytochemisty, reverse transcription
      polymerase chain reaction and western blotting. The results demonstrated that the
      majority of the differentiated cells presented classical dipolar and fusiform SC
      morphology. Notably, a large proportion of these cells expressed the three SC
      markers. These results suggest that hUCBMSCs can undergo directional
      differentiation into Schwann-like cells in vitro and may be an important source
      of SCs for the treatment of peripheral nerve defects with tissue-engineered
      artificial nerves.

PMID- 25369807
TI  - Targeting of vasoactive intestinal peptide receptor 2, VPAC2, a secretin family G
      protein coupled receptor, to primary cilia.

PMID- 25369808
TI  - Can a text message a week improve breastfeeding?
AB  - BACKGROUND: Breastfeeding is recognised as the optimal method for feeding infants
      with health gains made by reducing infectious diseases in infancy; and chronic
      diseases, including obesity, in childhood, adolescence and adulthood. Despite
      this, exclusivity and duration in developed countries remains resistant to
      improvement. The objectives of this research were to test if an automated mobile
      phone text messaging intervention, delivering one text message a week, could
      increase "any" breastfeeding rates and improve breastfeeding self-efficacy and
      coping. METHODS: Women were eligible to participate if they were: over eighteen
      years; had an infant less than three months old; were currently breastfeeding; no
      diagnosed mental illness; and used a mobile phone. Women in the intervention
      group received MumBubConnect, a text messaging service with automated responses
      delivered once a week for 8 weeks. Women in the comparison group received their
      usual care and were sampled two years after the intervention group. Data
      collection included online surveys at two time points, week zero and week nine,
      to measure breastfeeding exclusivity and duration, coping, emotions,
      accountability and self-efficacy. A range of statistical analyses were used to
      test for differences between groups. Hierarchical regression was used to
      investigate change in breastfeeding outcome, between groups, adjusting for co
      variates. RESULTS: The intervention group had 120 participants at commencement
      and 114 at completion, the comparison group had 114 participants at commencement
      and 86 at completion. MumBubConnect had a positive impact on the primary outcome
      of breastfeeding behaviors with women receiving the intervention more likely to
      continue exclusive breastfeeding; with a 6% decrease in exclusive breastfeeding
      in the intervention group, compared to a 14% decrease in the comparison group (p
      < 0.001). This remained significant after controlling for infant age, mother's
      income, education and delivery type (p = 0.04). Women in the intervention group
      demonstrated active coping and were less likely to display emotions-focussed
      coping (p < .001). There was no discernible statistical effect on self-efficacy
      or accountability. CONCLUSIONS: A fully automated text messaging services appears
      to improve exclusive breastfeeding duration. The service provides a well
      accepted, personalised support service that empowers women to actively resolve
      breastfeeding issues. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry: ACTRN12614001091695.

PMID- 25369809
TI  - Evaluation of risk of symptomatic cytomegalovirus reactivation in myeloma
      patients treated with tandem autologous stem cell transplantation and novel
      agents: a single-institution study.
AB  - The introduction of proteasome inhibitors and/or immunomodulators in the
      treatment of myeloma has led to an increase in viral infections, particularly in
      the Herpesviridae family. Previous studies about the risk of cytomegalovirus
      (CMV) reactivation after autologous stem cell transplantation (ASCT) have
      examined the clinical outcome after the first ASCT; however, only 1 study to date
      has investigated the risk of CMV reactivation after a second transplantation. To
      address this issue, we performed a retrospective chart review on 78 consecutive
      myeloma patients (median age 56 years) who underwent a tandem non-CD34(+)
      selected ASCT after induction treatment with either conventional chemotherapy (n
      = 42) or with novel agents (n = 36), respectively. All subjects had been
      mobilized and conditioned with cyclophosphamide plus granulocyte colony
      stimulating factor and melphalan alone, respectively. CMV DNA load in the blood
      has been determined by polymerase chain reaction in the case of a clinical
      suspicion of CMV reactivation; therefore, routine monitoring was not performed.
      Considering the outcome of both the first and the second transplantations, we
      observed a total of 13 episodes of symptomatic CMV reactivation (13/156, 8%), in
      12 subjects (12/78, 15%), all successfully treated. Eight subjects experienced a
      CMV reactivation after the first ASCT (8/78, 10%); however, only 1 of them (1/8,
      12%) experienced a CMV reactivation after the second transplantation. Conversely,
      4 CMV reactivations (6%) were observed after the second transplantation in the
      group of 70 patients who did not experience a CMV reactivation after the first
      ASCT. No statistically significant difference was observed between first and
      second ASCT (8/78, 10% vs. 5/78, 6%; P = 0.767). Univariate analysis showed that
      a pre-transplant treatment with novel agents was the only baseline factor
      significantly associated with the occurrence of post-ASCT CMV symptomatic
      reactivation after the first transplant (odds ratio [OR]: 9.897; 95% confidence
      interval [CI]: 1.154-84.840; P = 0.021) but not after the second transplant (OR:
      5.125; 95% CI: 0.546-48.119; P = 0.115). No end-organ disease or primary
      infection was documented. Our data suggest that second transplantation does not
      increase the risk of CMV reactivation in our patient population, when compared
      with the first one, and confirm the role of a pre-transplant treatment with novel
      agents as a risk factor for CMV symptomatic reactivation.

PMID- 25369810
TI  - Eukaryotic organisms in extreme acidic environments, the rio tinto case.
AB  - A major issue in microbial ecology is to identify the limits of life for growth
      and survival, and to understand the molecular mechanisms that define these
      limits. Thus, interest in the biodiversity and ecology of extreme environments
      has grown in recent years for several reasons. Some are basic and revolve around
      the idea that extreme environments are believed to reflect early Earth
      conditions. Others are related to the biotechnological potential of
      extremophiles. In this regard, the study of extremely acidic environments has
      become increasingly important since environmental acidity is often caused by
      microbial activity. Highly acidic environments are relatively scarce worldwide
      and are generally associated with volcanic activity or mining operations. For
      most acidic environments, low pH facilitates metal solubility, and therefore
      acidic waters tend to have high concentrations of heavy metals. However, highly
      acidic environments are usually inhabited by acidophilic and acidotolerant
      eukaryotic microorganisms such as algae, amoebas, ciliates, heliozoan and
      rotifers, not to mention filamentous fungi and yeasts. Here, we review the
      general trends concerning the diversity and ecophysiology of eukaryotic
      acidophilic microorganims, as well as summarize our latest results on this topic
      in one of the largest extreme acidic rivers, Rio Tinto (SW, Spain). 

PMID- 25369811
TI  - Domain structures and inter-domain interactions defining the holoenzyme
      architecture of archaeal d-family DNA polymerase.
AB  - Archaea-specific D-family DNA polymerase (PolD) forms a dimeric heterodimer
      consisting of two large polymerase subunits and two small exonuclease subunits.
      According to the protein-protein interactions identified among the domains of
      large and small subunits of PolD, a symmetrical model for the domain topology of
      the PolD holoenzyme is proposed. The experimental evidence supports various
      aspects of the model. The conserved amphipathic nature of the N-terminal putative
      alpha-helix of the large subunit plays a key role in the homodimeric assembly and
      the self-cyclization of the large subunit and is deeply involved in the archaeal
      PolD stability and activity. We also discuss the evolutional transformation from
      archaeal D-family to eukaryotic B-family polymerase on the basis of the
      structural information. 

PMID- 25369812
TI  - Phosphate Activation via Reduced Oxidation State Phosphorus (P). Mild Routes to
      Condensed-P Energy Currency Molecules.
AB  - The emergence of mechanisms for phosphorylating organic and inorganic molecules
      is a key step en route to the earliest living systems. At the heart of all
      contemporary biochemical systems reside reactive phosphorus (P) molecules (such
      as adenosine triphosphate, ATP) as energy currency molecules to drive endergonic
      metabolic processes and it has been proposed that a predecessor of such molecules
      could have been pyrophosphate [P2O74-; PPi(V)]. Arguably the most geologically
      plausible route to PPi(V) is dehydration of orthophosphate, Pi(V), normally a
      highly endergonic process in the absence of mechanisms for activating Pi(V). One
      possible solution to this problem recognizes the presence of reactive-P
      containing mineral phases, such as schreibersite [(Fe,Ni)3P] within meteorites
      whose abundance on the early Earth would likely have been significant during a
      putative Hadean-Archean heavy bombardment. Here, we propose that the reduced
      oxidation state P-oxyacid, H-phosphite [HPO32-; Pi(III)] could have activated
      Pi(V) towards condensation via the intermediacy of the condensed oxyacid
      pyrophosphite [H2P2O52-; PPi(III)]. We provide geologically plausible provenance
      for PPi(III) along with evidence of its ability to activate Pi(V) towards PPi(V)
      formation under mild conditions (80  degrees C) in water. 

PMID- 25369813
TI  - A necessary condition for coexistence of autocatalytic replicators in a prebiotic
      environment.
AB  - A necessary, but not sufficient, mathematical condition for the coexistence of
      short replicating species is presented here. The mathematical condition is
      obtained for a prebiotic environment, simulated as a fed-batch reactor, which
      combines monomer recycling, variable reaction order and a fixed monomer inlet
      flow with two replicator types and two monomer types. An extensive exploration of
      the parameter space in the model validates the robustness and efficiency of the
      mathematical condition, with nearly 1.7% of parameter sets meeting the condition
      and half of those exhibiting sustained coexistence. The results show that it is
      possible to generate a condition of coexistence, where two replicators sustain a
      linear growth simultaneously for a wide variety of chemistries, under an
      appropriate environment. The presence of multiple monomer types is critical to
      sustaining the coexistence of multiple replicator types. 

PMID- 25369814
TI  - Simple Organics and Biomonomers Identified in HCN Polymers: An Overview.
AB  - Hydrogen cyanide (HCN) is a ubiquitous molecule in the Universe. It is a compound
      that is easily produced in significant yields in prebiotic simulation experiments
      using a reducing atmosphere. HCN can spontaneously polymerise under a wide set of
      experimental conditions. It has even been proposed that HCN polymers could be
      present in objects such as asteroids, moons, planets and, in particular, comets.
      Moreover, it has been suggested that these polymers could play an important role
      in the origin of life. In this review, the simple organics and biomonomers that
      have been detected in HCN polymers, the analytical techniques and procedures that
      have been used to detect and characterise these molecules and an exhaustive
      classification of the experimental/environmental conditions that favour the
      formation of HCN polymers are summarised. Nucleobases, amino acids, carboxylic
      acids, cofactor derivatives and other compounds have been identified in HCN
      polymers. The great molecular diversity found in HCN polymers encourages their
      placement at the central core of a plausible protobiological system. 

PMID- 25369815
TI  - Stability toward High Energy Radiation of Non-Proteinogenic Amino Acids:
      Implications for the Origins of Life.
AB  - A series of non-proteinogenic amino acids, most of them found quite commonly in
      the meteorites known as carbonaceous chondrites, were subjected to solid state
      radiolysis in vacuum to a total radiation dose of 3.2 MGy corresponding to 23% of
      the total dose expected to be taken by organic molecules buried in asteroids and
      meteorites since the beginning of the solar system 4.6 * 109 years ago. The
      radiolyzed amino acids were studied by FT-IR spectroscopy, Differential Scanning
      Calorimetry (DSC) and by polarimety and Optical Rotatory Dispersion (ORD). It is
      shown that an important fraction of each amino acid is able to "survive" the
      massive dose of radiation, while the enantiomeric excess is partially preserved.
      Based on the results obtained, it is concluded that it is unsurprising to find
      amino acids even in enantiomeric excess in carbonaceous chondrites. 

PMID- 25369816
TI  - Model of biological quantum logic in DNA.
AB  - The DNA molecule has properties that allow it to act as a quantum logic
      processor. It has been demonstrated that there is coherent conduction of
      electrons longitudinally along the DNA molecule through pi stacking interactions
      of the aromatic nucleotide bases, and it has also been demonstrated that
      electrons moving longitudinally along the DNA molecule are subject to a very
      efficient electron spin filtering effect as the helicity of the DNA molecule
      interacts with the spin of the electron. This means that, in DNA, electrons are
      coherently conducted along a very efficient spin filter. Coherent electron spin
      is held in a logically and thermodynamically reversible chiral symmetry between
      the C2-endo and C3-endo enantiomers of the deoxyribose moiety in each nucleotide,
      which enables each nucleotide to function as a quantum gate. The symmetry break
      that provides for quantum decision in the system is determined by the spin
      direction of an electron that has an orbital angular momentum that is sufficient
      to overcome the energy barrier of the double well potential separating the C2
      endo and C3-endo enantiomers, and that enantiomeric energy barrier is appropriate
      to the Landauer limit of the energy necessary to randomize one bit of
      information. 

PMID- 25369817
TI  - Extremophiles and extreme environments.
AB  - Over the last decades, the study of extremophiles has providing ground breaking
      discoveries that challenge the paradigms of modern biology and make us rethink
      intriguing questions such as "what is life?", "what are the limits of life?", and
      "what are the fundamental features of life?". These findings and possibilities
      have made the study of life in extreme environments one of the most exciting
      areas of research in recent decades. However, despite the latest advances we are
      just in the beginning of exploring and characterizing the world of extremophiles.
      This special issue discusses several aspects of these fascinating organisms,
      exploring their habitats, biodiversity, ecology, evolution, genetics,
      biochemistry, and biotechnological applications in a collection of exciting
      reviews and original articles written by leading experts and research groups in
      the field. [...]. 

PMID- 25369818
TI  - Formaldehyde-a key monad of the biomolecular system.
AB  - Experiments will be presented and reviewed to support the hypothesis that the
      intrinsic reactivity of formaldehyde may lead to the formation of a rather
      comprehensive set of defined biomolecules, including D-glucose, thus fostering
      concepts of evolution considering the existence of a premetabolic system as a
      primordial step in the generation of life. 

PMID- 25369820
TI  - Mild cognitive impairment: a history and the state of current diagnostic
      criteria.
AB  - ABSTRACT Background: Mild cognitive impairment (MCI) is a diagnostic
      classification used to describe patients experiencing cognitive decline but
      without a corresponding impairment in daily functioning. Over the years, MCI
      diagnostic criteria have undergone major changes that correspond to advancements
      in research. Despite these advancements, current diagnostic criteria for MCI
      contain issues that are reflected in the research literature. Methods: A review
      of the available MCI literature was conducted with emphasis given to tracing MCI
      from its conceptual underpinnings to the most current diagnostic criteria. A
      clinical vignette is utilized to highlight some of the limitations of current MCI
      diagnostic criteria. Results: Issues are encountered when applying MCI diagnostic
      criteria due to poor standardization. Estimates of prevalence, incidence, and
      rates of conversion from MCI to dementia reflect these issues. Conclusions: MCI
      diagnostic criteria are in need of greater standardization. Recommendations for
      future research are provided that could potentially bring more uniformity to the
      diagnostic criteria for MCI and, therefore, more consistency to the research
      literature.

PMID- 25369819
TI  - Natural pyrrhotite as a catalyst in prebiotic chemical evolution.
AB  - The idea of an autotrophic organism as the first living being on Earth leads to
      the hypothesis of a protometabolic, complex chemical system. In one of the main
      hypotheses, the first metabolic systems emerged from the interaction between
      sulfide minerals and/or soluble iron-sulfide complexes and fluids rich in
      inorganic precursors, which are reduced and derived from crustal or mantle
      activity. Within this context, the possible catalytic role of pyrrhotite, one of
      the most abundant sulfide minerals, in biomimetic redox and carbon fixation
      reactions was studied. Our results showed that pyrrhotite, under simulated
      hydrothermal conditions, could catalyze the pyruvate synthesis from lactate and
      that a dynamic system formed by coupling iron metal and iron-sulfur species in an
      electrochemical cell could promote carbon fixation from thioacetate esters. 

PMID- 25369821
TI  - Aliskiren in an alternate-day administration schedule in hypertensive albuminuric
      patients.
AB  - OBJECTIVE: It has been suggested that aliskiren has a long half-life and
      maintains a blood pressure (BP)-lowering effect following a missed dose. We
      tested the hypothesis that every other day (eod) administration of aliskiren has
      the same effects as the once daily (od) dosing in albuminuric hypertensive
      patients. METHODS: Fifteen hypertensive patients, after a 4-week wash-out period
      on clonidine, received 300 mg aliskiren od as the sole treatment. In patients who
      remained out of target, other nonrenin-angiotensin system blockers were added.
      Patients who completed a 24-week (w24) treatment period were switched to eod
      administration of aliskiren for an additional period of 24 weeks (w48). RESULTS:
      Thirteen patients completed the full study protocol. The mean office BP was
      reduced at the end of w24 (-9/3 mmHg), a reduction that continued to be observed
      at w48 (-11/1 mmHg). At the end of the study, the 48 h ambulatory BP monitoring
      was divided into two 24 h periods. The mean 24 h systolic BP, and the mean
      daytime systolic and diastolic BP were significantly lower (P<0.05) in the first
      24 h (when aliskiren was taken) compared with the second period. Central
      hemodynamics showed no significant differences at any time during monitoring.
      Administration of aliskiren resulted in a median reduction of urine
      albumin/creatinine ratio of 103 mg/g (od) and 102 mg/g (eod). Differences in
      plasma renin activity, plasma renin concentration, and aldosterone-level
      measurements were not significant. CONCLUSION: The BP-lowering effect of eod
      aliskiren administration, although adequate, is less efficient compared with od
      administration, despite the fact that in terms of reducing albuminuria, it
      appears to be effective.

PMID- 25369822
TI  - Clinical approach to noninvasive and invasive blood pressure monitoring in end
      stage renal disease patients on dialysis.

PMID- 25369823
TI  - In response: Comment on noninvasive and invasive blood pressure monitoring in end
      stage renal disease patients on dialysis.

PMID- 25369824
TI  - Blood pressure monitoring through pharmacies and team-based care of hypertension.

PMID- 25369825
TI  - Drug-induced subacute cutaneous lupus erythematosus associated with docetaxel
      chemotherapy: a case report.
AB  - BACKGROUND: Drug-induced subacute cutaneous lupus erythematosus is an uncommon
      disorder associated with the use of pharmacological agents including systemic
      chemotherapy. CASE PRESENTATION: We report a case of docetaxel-induced subacute
      cutaneous lupus erythematosus in a 60-year-old Caucasian female with Sjogren's
      syndrome diagnosed 2 months after receiving docetaxel as part of the adjuvant FEC
      D (5-fluorouracil, epirubicin, cyclophosphamide, docetaxel) chemotherapy protocol
      for early stage breast cancer. Although the exact mechanisms behind the
      autoimmune response elicited by docetaxel are unclear, the involvement of anti
      SSA/Ro antibodies has been implicated. CONCLUSION: This case highlights the
      symptom severity and clinical course of docetaxel-induced subacute cutaneous
      lupus erythematosus, and highlights the importance of recognizing this uncommon
      but potentially severe chemotherapy-associated cutaneous reaction.

PMID- 25369826
TI  - Changes in body mass index, waist and hip circumferences, waist to hip ratio and
      risk of all-cause mortality in men.
AB  - BACKGROUND: There is a paucity of data about the impact of changes in
      anthropometric measurements on the risk of mortality events, especially in men.
      METHODS: The study sample consists of 1805 Iranian men, aged ? 30 years, free
      from cardiovascular disease at baseline; they had undergone health examinations
      in both phases I (1999-2001) and II (2001-2003) and were followed up until March
      2010. Participants were categorized by changes in anthropometric measurements
      into four groups: Group 1, change percentage<-5%; Group 2, -5% ? change
      percentages<+5%; Group 3, 5% ? change percentage<10%; and Group 4, change
      percentage ? 10%. Cox proportional hazard regression was performed to assess the
      hazard ratios (HRs) of the anthropometric changes for all-cause mortality, given
      group 2 as the reference. RESULTS: During 6.6 years of follow-up, 88 cases of
      mortality events occurred. The confounder-adjusted multivariate HRs for the
      first, third and fourth groups of hip circumference (HC) changes were 3.13(1.28
      7.64), 0.75(0.43-1.31) and 0.82(0.23-2.99); the corresponding values for waist to
      hip ratio (WHR) change were 1.80(0.75-4.33), 1.21(0.70-2.1) and 2.32(1.25-4.3).
      After further adjustment for mediator covariates, results did not change. The
      equivalent values for body mass index and waist circumference did not reach
      statistical significance. CONCLUSIONS: In Middle Eastern Caucasian men, increase
      in WHR was associated with incident mortality, which was more prominent in those
      with ? 10% increase in the ratio. Moreover, decrease in HC was highly associated
      with excess risk of mortality.

PMID- 25369827
TI  - The effect of a multi-strain probiotic on the resistance toward Escherichia coli
      challenge in a randomized, placebo-controlled, double-blind intervention study.
AB  - BACKGROUND: Several probiotic strains have been shown to enhance human resistance
      to infectious disease. It is speculated that these strains may impose this effect
      by excretion of anti-microbial components, by competing with pathogens for
      intestinal nutrients and/or mucosal adhesion sites or modulating the immune
      system. OBJECTIVE: A parallel, double-blind, placebo-controlled 4-week
      intervention was performed in healthy males, to study the effect of a blend of
      probiotic bacteria (Lactobacillus helveticus Rosell-52, Lactobacillus rhamnosus
      Rosell-11, Bifidobacterium longum ssp. longum Rosell-175) and a probiotic yeast
      (Saccharomyces cerevisiae var boulardii CNCM I-1079) on enterotoxigenic
      Escherichia coli (ETEC) challenge. Primary outcomes studied were fecal ETEC
      excretion and total fecal output per day. SUBJECTS/METHODS: Subjects were
      randomized to the probiotic (5 * 10(9) colony-forming units (CFUs); twice daily;
      n=30) or placebo group (twice daily; n=30). After 2 weeks, subjects were orally
      challenged with a live attenuated ETEC (3 * 10(9) CFU), previously demonstrated
      to induce mild, short-lived symptoms of a foodborne infection. Before and after
      ETEC challenge, subjects collected 24 h fecal samples. Compliance to study
      guidelines, stool consistency (Bristol Stool Score), stool frequency, and
      frequency and severity of gastrointestinal (GI) complaints were recorded by the
      subjects on a Daily Record Questionnaire. RESULTS: ETEC challenge induced a
      significant increase in fecal ETEC excretion in both groups. However, a
      statistically significant increase in fecal output was only observed in the
      probiotic group. ETEC challenge resulted in a decrease in the percentage of fecal
      dry weight, and an increase in reported Bristol Stool Score, stool frequency and
      GI complaints. Dietary probiotics significantly decreased the percentage of fecal
      dry weight. In addition, ETEC increased C-reactive protein, total secretory
      Immunoglobulin A (IgA) and Immunoglobulin G Colonization Factor Antigen II.
      CONCLUSION: Dietary probiotics did not increase resistance to oral attenuated
      ETEC challenge in human subjects.

PMID- 25369828
TI  - Association between nutritional risk and routine clinical laboratory measurements
      and adverse outcomes: a prospective study in hospitalized patients of Wuhan
      Tongji Hospital.
AB  - BACKGROUND/OBJECTIVES: Nutritional risk screening (NRS-2002) and routine clinical
      laboratory measurements (RCLMs) had been shown to have a predictive value in
      adverse outcomes in some studies, respectively. This study analyzed the
      association between NRS-2002 and RCLMs and estimated their prospective value in
      predicting adverse outcomes. SUBJECTS/METHODS: A total of 916 hospitalized
      patients were screened on admission with NRS-2002 and Subjective Global
      Assessment; RCLMs, which include blood test, kidney and liver function and
      electrolytes, were recorded. Diagnosis, nutritional support, surgery,
      radiotherapy, chemotherapy, complications, mortality and hospital stay during
      hospitalization were collected. The X(2)-test, odds ratios with 95% confidence
      intervals, kappa (k) statistic and regression analyses were conducted. RESULTS:
      An overall 48.1% of the 916 patients were at nutritional risk on admission.
      Comparing 'at risk' with 'no risk', a significantly higher incidence of
      abnormality was found not only in nutritional markers but also in other
      parameters of RCLMs (OR ranged from 1.5 to 3.5). Regression analyses showed that
      'at risk' determined at admission was not a significant predictor of adverse
      outcomes after adjusting for other confounding factors, although it was a strong
      predictor in univariate analysis, whereas hypoalbuminemia, low total lymphocyte
      count, abnormality of hepatic and renal function were predictors after adjusting
      for confounders. CONCLUSIONS: The findings suggest that NRS-2002 might be a
      global index of 'sickness' rather than be only a nutritional screening tool. It
      being rated once at admission is insufficient and should be repeated for using it
      as a predictor, whereas RCLMs routinely measured at admission may be able to be
      used to predict adverse outcomes.

PMID- 25369829
TI  - Effects of Mediterranean-style diet on glycemic control, weight loss and
      cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis.
AB  - BACKGROUND/OBJECTIVES: Studies suggest that the Mediterranean-style diet (MSD)
      may improve glucose metabolism in patients with type 2 diabetes (T2D), but the
      results are inconsistent. We conducted a meta-analysis of randomized controlled
      trials (RCTs) to explore the effects of MSD on glycemic control, weight loss and
      cardiovascular risk factors in T2D patients. SUBJECTS/METHODS: We performed
      searches of EMBASE, Cochrane Library and PubMed databases up to February 2014. We
      included RCTs that compared the MSD with control diets in patients with T2D.
      Effect size was estimated as mean difference with 95% confidence interval (CI) by
      using random effect models. RESULTS: The meta-analysis included nine studies with
      1178 patients. Compared with control diets, MSD led to greater reductions in
      hemoglobin A1c (mean difference, -0.30; 95% CI, -0.46 to -0.14), fasting plasma
      glucose (-0.72 mmol/l; CI, -1.24 to -0.21), fasting insulin (-0.55 MUU/ml; CI, 
      0.81 to -0.29), body mass index (-0.29 kg/m(2); CI, -0.46 to -0.12) and body
      weight (-0.29 kg; CI, -0.55 to -0.04). Likewise, concentrations of total
      cholesterol and triglyceride were decreased (-0.14 mmol/l; CI, -0.19 to -0.09 and
      -0.29 mmol/l; CI, -0.47 to -0.10, respectively), and high-density lipoprotein was
      increased (0.06 mmol/l; CI, 0.02 to 0.10). In addition, MSD was associated with a
      decline of 1.45 mm Hg (CI, -1.97 to -0.94) for systolic blood pressure and 1.41
      mm Hg (CI, -1.84 to -0.97) for diastolic blood pressure. CONCLUSIONS: The present
      meta-analysis provides evidence that MSD improves outcomes of glycemic control,
      body weight and cardiovascular risk factors in T2D patients.

PMID- 25369830
TI  - Handgrip strength measurement as a predictor of hospitalization costs.
AB  - BACKGROUND: Undernutrition status at hospital admission is related to increased
      hospital costs. Handgrip strength (HGS) is an indicator of undernutrition, but
      the ability of HGS to predict hospitalization costs has yet to be studied.
      OBJECTIVE: To explore whether HGS measurement at hospital admission can predict
      patient's hospitalization costs. SUBJECTS/METHODS: A prospective study was
      conducted in a university hospital. Inpatient's (n=637) HGS and undernutrition
      status by Patient-Generated Subjective Global Assessment were ascertained.
      Multivariable linear regression analysis, computing HGS quartiles by sex
      (reference: fourth quartile, highest), was conducted in order to identify the
      independent predictors of hospitalization costs. Costs were evaluated through
      percentage deviation from the mean cost, after adjustment for patients'
      characteristics, disease severity and undernutrition status. RESULTS: Being in
      the first or second HGS quartiles at hospital admission increased patient's
      hospitalization costs, respectively, by 17.5% (95% confidence interval: 2.7-32.3)
      and 21.4% (7.5-35.3), which translated into an increase from ?375 (58-692) to
      ?458 (161-756). After the additional adjustment for undernutrition status, being
      in the first or second HGS quartiles had, respectively, an economic impact of
      16.6% (1.9-31.2) and 20.0% (6.2-33.8), corresponding to an increase in
      hospitalization expenditure from ?356 (41-668) to ?428 (133-724). CONCLUSIONS:
      Low HGS at hospital admission is associated with increased hospitalization costs
      of between 16.6 and 20.0% after controlling for possible confounders, including
      undernutrition status. HGS is an inexpensive, noninvasive and easy-to-use method
      that has clinical potential to predict hospitalization costs.

PMID- 25369831
TI  - Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Although postmenopausal combined hormone replacement therapy reduces
      the risk of hip fracture, long-term use may be associated with an increased risk
      of breast cancer, and in women more than 10 years after menopause it is
      associated with an increased risk of cardiovascular disease. Isoflavones, because
      of preferential binding to estrogen receptor beta, may retain the beneficial
      effects on bone but lessen the adverse effects on the breast. OBJECTIVE: The
      objective of this study was to study the effects of an isoflavone obtained from
      red clover (Rimostil) on bone mineral density, and on low-density lipoprotein
      (LDL) cholesterol. DESIGN: In a double-blind, randomized, placebo-controlled
      trial, 50 mg of Rimostil was given to women who were menopausal for at least 1
      year. Bone mineral density of the spine, femoral neck and forearm and serum LDL
      cholesterol were measured at baseline and at 6-month intervals. The duration of
      follow-up was 2 years. RESULTS: There was no beneficial effect of Rimostil on
      bone density at any site. There was a 12% fall in serum LDL cholesterol in the
      Rimostil-treated arm, which was significantly greater than the 2% drop seen in
      the control arm (P=0.005).

PMID- 25369832
TI  - Male longevity in Sardinia, a review of historical sources supporting a causal
      link with dietary factors.
AB  - The identification of a hot spot of exceptional longevity, the Longevity Blue
      Zone (LBZ), in the mountain population of Sardinia has aroused considerable
      interest toward its traditional food as one of the potential causal factors. This
      preliminary study on the traditional Sardinian diet has been supported by the
      literature available, which has been carefully reviewed and compared. Up to a
      short time ago, the LBZ population depended mostly upon livestock rearing, and
      consumption of animal-derived foods was relatively higher than in the rest of the
      island. The nutrition transition (NT) in urbanized and lowland areas began in the
      mid-1950s, fueled by economic development, whereas in the LBZ it started later
      owing to prolonged resistance to change by a society organized around a rather
      efficient pastoral economy. Even nowadays a large proportion of the population in
      this area still follows the traditional diet based on cereal-derived foods and
      dairy products. The LBZ cohorts comprising individuals who were of a mature age
      when NT began may have benefited both from the high-quality, albeit rather
      monotonous, traditional diet to which they had been exposed most of their life
      and from the transitional diet, which introduced positive changes such as more
      variety, increased consumption of fruits and vegetables and moderate meat intake.
      It could be speculated that these changes may have brought substantial health
      benefits to this particular aging group, which was in need of nutrient-rich food
      at this specific time in life, thereby resulting in a decreased mortality risk
      and, in turn, life-span extension. 

PMID- 25369833
TI  - Re-building Daniell cell with a Li-ion exchange film.
AB  - Daniell cell (i.e. Zn-Cu battery) is widely used in chemistry curricula to
      illustrate how batteries work, although it has been supplanted in the late 19th
      century by more modern battery designs because of Cu(2+)-crossover-induced self
      discharge and un-rechargeable characteristic. Herein, it is re-built by using a
      ceramic Li-ion exchange film to separate Cu and Zn electrodes for preventing
      Cu(2+)-crossover between two electrodes. The re-built Zn-Cu battery can be cycled
      for 150 times without capacity attenuation and self-discharge, and displays a
      theoretical energy density of 68.3 Wh kg(-1). It is more important that both
      electrodes of the battery are renewable, reusable, low toxicity and
      environmentally friendly. Owing to these advantages mentioned above, the re-built
      Daniell cell can be considered as a promising and green stationary power source
      for large-scale energy storage.

PMID- 25369834
TI  - p53 suppresses stress-induced cellular senescence via regulation of autophagy
      under the deprivation of serum.
AB  - The tumor suppressor p53 is widely known for its ability to induce cell cycle
      arrest or cell death, therefore preventing neoplastic progression. Previous
      studies have demonstrated novel roles for p53 in the regulation of autophagy and
      senescence. p53 can not only exert cell cycle-arresting and senescence-promoting
      or suppressing functions, but can also induce autophagic flux, particularly under
      conditions of nutrient deprivation. The present study demonstrated that p53 was
      capable of activating autophagy, which permits cell survival under conditions of
      serum starvation, and suppresses cellular senescence through inhibition of the
      mammalian target of rapamycin pathway. These results suggest that active
      autophagy may be a potential mechanism by which p53 suppresses cellular
      senescence, in response to serum starvation. The findings of the present study
      provide a potential mechanism for suppression of senescence by p53. 

PMID- 25369835
TI  - Intracranial Extension of an Orbital Epidermoid Cyst.
AB  - Epidermoid and dermoid cysts represent the most common cystic lesions of the
      orbit and commonly arise from bony sutures or the intradiplpoic space of orbital
      bones. Massive intracranial extension of an epidermoid cyst arising from the
      intradiploic space of an orbital bone is very rarely seen. We present a case of a
      55-year-old male who was incidentally found to have massive intracranial
      extension of an intradiploic epidermoid cyst of the superolateral orbital bone
      with minimal symptoms. The cyst was completely excised via a pterional craniotomy
      and lateral orbitotomy by neurosurgery and oculoplastic surgery teams. The
      patient suffered no complications and is doing very well.

PMID- 25369836
TI  - Review of AlloDerm Acellular Human Dermis Regenerative Tissue Matrix in Multiple
      Types of Oculofacial Plastic and Reconstructive Surgery.
AB  - PURPOSE: AlloDerm acellular human dermis is used for repair or replacement of
      damaged or inadequate skin tissue. It has been used successfully in multiple
      types of surgeries, including abdominal wall reconstruction, breast
      reconstruction, and head and neck reconstruction. Its application to ophthalmic
      plastic and reconstructive surgery is less well described. This study seeks to
      evaluate the efficacy and factors influencing surgical outcomes using Alloderm in
      multiple types of oculofacial plastic surgery. METHODS: Institutional Review
      Board-approved retrospective review of 84 patients who underwent surgical
      procedures using Alloderm. Preoperative demographic data, comorbidities, smoking,
      clinical etiology, surgical methods, Alloderm type, and outcome (cosmetic and
      functional) were evaluated. RESULTS: This study included 84 patients, accounting
      for a total of 98 procedures. Mean age was 52.5 years (3-93 years). Etiologies
      necessitating surgery included malignancy in 26 patients (31.0%), trauma in 19
      patients (22.6%), congenital lesions in 15 patients (17.9%), and senile change in
      11 patients (13.1%). Surgical procedures included lower eyelid posterior lamella
      elongation, socket and fornix reconstruction, scar repair, patch grafts, and
      filler. Mean duration of follow up was 530 days. Overall, 92.8% of patients had
      favorable outcomes. Factors associated with significantly worse outcomes included
      smoking, congenital anomaly etiologies, and previous graft/flaps in the same area
      (p = 0.03, p = 0.029, and p = 0.007, respectively). CONCLUSIONS: This study
      suggests that Alloderm acellular human dermis can be used safely and effectively
      in multiple types of oculofacial procedures. Smoking, congenital anomaly
      etiologies, and previous graft/flap were associated with poor cosmetic and
      functional outcomes.

PMID- 25369837
TI  - Twelve-Year Experience of Lester Jones Tubes-Results and Comparison of 3
      Different Tube Types.
AB  - PURPOSE: Conjunctivodacryorhinostomy with insertion of a bypass Lester Jones tube
      is effective in treating epiphora due to canalicular failure. There is little
      information in the literature that directly compares different types of tubes. We
      report our results of Jones tube placements over a 12-year period with comparison
      of 3 tube types: plain, frosted, and a new tube with an additional flexible
      internal silicone flange (StopLoss Jones tube). METHODS: Case notes review of a
      single surgeon consecutive series of patients having Jones tube placement.
      RESULTS: One hundred twenty-seven tubes were inserted in 81 eyes of 65 patients.
      Information on 121 tubes was available for comparison (67 plain, 25 frosted, 29
      StopLoos Jones Tube [SLJT]), with flange sizes 3.5 and 4.0 mm. There were 31
      males, 34 females, mean age 59 years. After mean follow up of 20 months (range
      0.5-108), there were no complications in 50% of tube insertions. Forty-three
      percentage of tubes needed replacing. The overall rate of complications was
      higher with a 3.5-mm flange tube than with a 4.0-mm flange (67% vs. 43%). There
      were no cases of extrusion in the SLJT group after follow up to a maximum of 25
      months. The risk of extrusion for both frosted and plain tubes was significantly
      higher than for SLJT (p = 0.0040). There was no significant difference in the
      risk of extrusion between frosted and plain tubes. Overall, the risk of
      complications requiring tube replacement was not significantly different between
      frosted and plain tubes; however, the risk was significantly higher with both
      frosted and plain tubes compared with the SLJT (p = 0.036 and p = 0.042,
      respectively). Patient satisfaction was full in 86% and moderate in a further 5%
      of patients. CONCLUSIONS: Although patient satisfaction with LJT surgery is high,
      complications occur frequently, although seem to be less common with the larger
      4.0 mm flange. Frosted tubes do not protect against tube displacement. The
      addition of the internal silicone flange on the SLJT seems to prevent the
      previously common problem of extrusion.

PMID- 25369840
TI  - Mental health consumer and carer participation: why we bother.

PMID- 25369838
TI  - ZBTB20 regulates nociception and pain sensation by modulating TRP channel
      expression in nociceptive sensory neurons.
AB  - In mammals, pain sensation is initiated by the detection of noxious stimuli
      through specialized transduction ion channels and receptors in nociceptive
      sensory neurons. Transient receptor potential (TRP) channels are the key sensory
      transducers that confer nociceptors distinct sensory modalities. However, the
      regulatory mechanisms about their expression are poorly defined. Here we show
      that the zinc-finger protein ZBTB20 regulates TRP channels expression in
      nociceptors. ZBTB20 is highly expressed in nociceptive sensory neurons of dorsal
      root ganglia. Disruption of ZBTB20 in nociceptors led to a marked decrease in the
      expression levels of TRPV1, TRPA1 and TRPM8 and the response of calcium flux and
      whole-cell currents evoked by their respective specific agonists. Phenotypically,
      the mice lacking ZBTB20 specifically in nociceptors showed a defect in
      nociception and pain sensation in response to thermal, mechanical and
      inflammatory stimulation. Our findings point to ZBTB20 as a critical regulator of
      nociception and pain sensation by modulating TRP channels expression in
      nociceptors. 

PMID- 25369841
TI  - Supporting families of parents with mental illness in general practice.
AB  - The general-practice setting provides a unique opportunity to positively
      influence the impact of mental illness on individuals and families. Intervention
      can begin from the moment an individual seeks professional help. Using a family
      focused approach, and supporting parents to develop practical strategies to
      promote resilience in their children, can aid parents' recovery and promote the
      optimal emotional wellbeing of their children. We suggest a family-orientated
      therapeutic approach relevant to the general-practice setting, with particular
      consideration of the value of communicating with children according to the
      child's stage of emotional development. 

PMID- 25369839
TI  - Human cancer databases (review).
AB  - Cancer is one of the four major non-communicable diseases (NCD), responsible for
      ~14.6% of all human deaths. Currently, there are >100 different known types of
      cancer and >500 genes involved in cancer. Ongoing research efforts have been
      focused on cancer etiology and therapy. As a result, there is an exponential
      growth of cancer-associated data from diverse resources, such as scientific
      publications, genome-wide association studies, gene expression experiments, gene
      gene or protein-protein interaction data, enzymatic assays, epigenomics,
      immunomics and cytogenetics, stored in relevant repositories. These data are
      complex and heterogeneous, ranging from unprocessed, unstructured data in the
      form of raw sequences and polymorphisms to well-annotated, structured data.
      Consequently, the storage, mining, retrieval and analysis of these data in an
      efficient and meaningful manner pose a major challenge to biomedical
      investigators. In the current review, we present the central, publicly accessible
      databases that contain data pertinent to cancer, the resources available for
      delivering and analyzing information from these databases, as well as databases
      dedicated to specific types of cancer. Examples for this wealth of cancer-related
      information and bioinformatic tools have also been provided.

PMID- 25369842
TI  - Family matters: infants, toddlers and preschoolers of parents affected by mental
      illness.

PMID- 25369843
TI  - Intervention programs for children whose parents have a mental illness: a review.
AB  - OBJECTIVE: To identify and describe intervention programs to improve outcomes for
      children whose parents have a mental illness. DATA SOURCES: Grey and black
      literature was sourced from (i) three previous reviews/scoping studies, (ii)
      PsycINFO and MEDLINE searches of English, German and Dutch papers, and (iii) in
      consultation with researchers, clinicians, consumers and carers in the field.
      STUDY SELECTION: Only programs specifically targeting children whose parent/s
      have a mental illness. No restrictions were placed on study quality. DATA
      EXTRACTION: Program description, target group and evidence base. DATA SYNTHESIS:
      Programs from Australia, Europe and North America were found and collated into
      (i) family interventions, (ii) peer-support programs, (iii) online interventions
      and (iv) bibliotherapy. Some programs had been evaluated, with promising results.
      Others had minimal or no evaluation. CONCLUSIONS: The core component across
      programs is the provision of psychosocial education to children about mental
      illness. More rigorous research is required to establish the conditions through
      which children's outcomes are enhanced.

PMID- 25369844
TI  - Preventive interventions for children of parents with depression: international
      perspectives.

PMID- 25369845
TI  - Obstetric and neonatal outcomes of pregnant women with severe mental illness at a
      specialist antenatal clinic.
AB  - OBJECTIVE: To evaluate the obstetric and neonatal outcomes of pregnant women with
      severe mental illness (SMI) who attended a specialist multidisciplinary antenatal
      clinic in Perth, Western Australia. DESIGN, SETTING AND PARTICIPANTS: A
      retrospective case-note audit of outcomes from the Childbirth and Mental Illness
      Antenatal Clinic (CAMI clinic) at King Edward Memorial Hospital for pregnant
      women with severe mental illness (SMI), aged 18-41 years, who gave birth between
      December 2007 and April 2011, and their babies. MAIN OUTCOME MEASURES: Obstetric
      and neonatal outcomes for 138 women and newborns from singleton live births. Data
      were compared between three diagnostic groups (schizophrenia, bipolar and non
      psychotic SMI), and with WA obstetric and perinatal statistics for 2008. RESULTS:
      44 women with schizophrenia, 56 with bipolar disorder and 38 with non-psychotic
      SMI attended antenatal care for an average of 7.7 (SD, 3.3) visits. The
      proportion of women who smoked tobacco was significantly higher than that in the
      WA antenatal population (46% v 15%; P < 0.0001). Alcohol use, illicit substance
      use and psychotropic medication exposure during pregnancy were high. The women
      were at increased risk of developing gestational diabetes mellitus (15% v 4%; P <
      0.0001) and pre-eclampsia (9% v 3%; P < 0.0001), and birth complications were
      more common. Babies born to CAMI clinic women were less likely to have Apgar
      scores >= 8 at 1 minute and 5 minutes. Pregnant women with schizophrenia had more
      psychiatric relapses during pregnancy, and had more statutory child welfare
      involvement. Gestational age at birth and infant birth weights were similar for
      the pregnant women with SMI and the WA population in 2008. CONCLUSIONS: Women
      attending our specialist clinic had increased rates of obstetric and neonatal
      complications compared with the general population, and were exposed to a cluster
      of risk factors. We report encouraging trends in antenatal attendance,
      gestational age at birth, and birth weights. Managing pregnant women with SMI
      will require a comprehensive approach aimed at early detection of obstetric
      complications and psychosocial difficulties, as well as neonatal monitoring.
      Optimising prepregnancy maternal health and welfare may also be of benefit.

PMID- 25369846
TI  - Enhancing parenting skills for parents with mental illness: the Mental Health
      Positive Parenting Program.
AB  - OBJECTIVE: To determine the effect of the Mental Health Positive Parenting
      Program (MHPPP) on parenting practices of parents reporting a mental health
      problem. DESIGN, SETTING AND PARTICIPANTS: A prospective before-and-after
      examination of positive parenting skills and parent-reported child outcomes among
      parents of children aged 2-10 years who had self-reported a mental health
      problem. One hundred and eleven (85.4%) of 130 parents who commenced the MHPPP
      completed the program. Of these, 77.5% (n = 86) completed both before- and after
      intervention measures. The MHPPP was conducted across four community health
      centres. INTERVENTION: A 10-week intervention was tailored to parents with a
      mental health problem. The intervention was divided into a 6-week group parenting
      program based on the Positive Parenting Program and four weekly home visits. MAIN
      OUTCOME MEASURES: Parental discipline practices and children's behaviour were
      measured by the Parenting Scale (PS) and the Eyberg Child Behavior Inventory
      (ECBI), respectively. RESULTS: Following the MHPPP, parents scored significantly
      lower on each of the PS subscales: laxness (Z = - 6.23; P < 0.001), over
      reactivity (Z = - 7.15; P < 0.001) and verbosity (Z = - 6.59; P < 0.001); and
      significantly lower on both ECBI subscales: intensity (Z = - 7.08, P < 0.001) and
      problem (Z = - 7.57; P < 0.001). CONCLUSIONS: Our findings suggest the MHPPP can
      reduce the number of dysfunctional parenting strategies and parent-reported child
      behavioural problems. The MHPPP is a promising avenue for early intervention in
      this population.

PMID- 25369847
TI  - Fathers with mental illness: implications for clinicians and health services.
AB  - A significant proportion of fathers living with their natural, adopted, step or
      foster children experience mental illness. Psychiatric illness among fathers can
      have a devastating impact on children's wellbeing, and even milder forms of
      paternal mental illness can have serious developmental effects on children. While
      several pathways linking paternal mental illness with poor child outcomes have
      been identified, fathers' impaired parenting is an important, potentially
      malleable factor. Clinicians can assist fathers with mental illness and their
      families by proactively inquiring about children and by exploring fathering
      focused psychological support. 

PMID- 25369848
TI  - Goal setting within family care planning: families with complex needs.
AB  - OBJECTIVE: To identify the key goals that are established by children and parents
      from families in which parents have substance use and/or mental health problems,
      and the level of progress achieved towards goals over 1 year of case management.
      DESIGN, SETTING AND PARTICIPANTS: Participants from three rural sites of a New
      South Wales non-government agency completed family care plans between 2008 and
      2010. They included 44 parents and 41 children from 37 families where at least
      one parent had a dual diagnosis or mental illness. Family care plans were
      analysed to identify the frequency and progress of child and parent goals across
      11 domains. MAIN OUTCOME MEASURES: Goals identified by parents and children, and
      change scores over a 12-month period. RESULTS: Children most frequently set goals
      to enhance their knowledge of mental illness, schooling, family connectedness and
      interpersonal skills. Parents most frequently set goals to improve their
      knowledge of mental health. Children recorded greatest goal achievement: in
      enhancing their mental health knowledge, community/social connectedness and
      accommodation needs. Parents recorded most goal progress in understanding
      developmental milestones of their children. CONCLUSIONS: Goal setting appears to
      be an important mechanism for assisting families with complex needs. Clinicians
      need to address the mental health literacy of families where a parent has a
      substance use problem and/or mental illness.

PMID- 25369849
TI  - Parental mental illness is a family matter.

PMID- 25369850
TI  - Children whose parents have a mental illness: prevalence, need and treatment.
AB  - Up to one in five young people live in families with a parent who has a mental
      illness. There are various genetic, individual, family and environmental risk
      factors for children living in these families. Outcomes for children vary
      according to factors related to a parent's mental illness as well as certain
      environmental protective and risk factors, related to the family, social support
      and community. Health care workers need to acknowledge their patients' parenting
      roles and responsibilities and the needs of other family members, especially
      children. 

PMID- 25369851
TI  - Unravelling the multilayer growth of the fullerene C60 in real time.
AB  - Molecular semiconductors are increasingly used in devices, but understanding of
      elementary nanoscopic processes in molecular film growth is in its infancy. Here
      we use real-time in situ specular and diffuse X-ray scattering in combination
      with kinetic Monte Carlo simulations to study C60 nucleation and multilayer
      growth. We determine a self-consistent set of energy parameters describing both
      intra- and interlayer diffusion processes in C60 growth. This approach yields an
      effective Ehrlich-Schwoebel barrier of EES=110 meV, diffusion barrier of ED=540
      meV and binding energy of EB=130 meV. Analysing the particle-resolved dynamics,
      we find that the lateral diffusion is similar to colloids, but characterized by
      an atom-like Schwoebel barrier. Our results contribute to a fundamental
      understanding of molecular growth processes in a system, which forms an important
      intermediate case between atoms and colloids. 

PMID- 25369852
TI  - A Dose-Finding Method Based on Multiple Dosing in Two-Agent Combination Phase I
      Trials.
AB  - Here, we developed a new dose-finding method that partitions a cohort of patients
      based on the number of dose combinations within a prespecified acceptable
      toxicity range in two-agent combination Phase I trials. In the proposed method,
      patients in the same cohort are partitioned according to several dose
      combinations, although most of the existing methods allocate patients in the same
      cohort according to a single-dose combination. We compared the operating
      characteristics of the proposed and existing methods through simulation studies. 

PMID- 25369853
TI  - Phase-sensitive dual-inversion recovery for accelerated carotid vessel wall
      imaging.
AB  - OBJECTIVES: Dual-inversion recovery (DIR) is widely used for magnetic resonance
      vessel wall imaging. However, optimal contrast may be difficult to obtain and is
      subject to RR variability. Furthermore, DIR imaging is time-inefficient and
      multislice acquisitions may lead to prolonged scanning times. Therefore, an
      extension of phase-sensitive (PS) DIR is proposed for carotid vessel wall
      imaging. METHODS: The statistical distribution of the phase signal after DIR is
      probed to segment carotid lumens and suppress their residual blood signal. The
      proposed PS-DIR technique was characterized over a broad range of inversion
      times. Multislice imaging was then implemented by interleaving the acquisition of
      3 slices after DIR. Quantitative evaluation was then performed in healthy adult
      subjects and compared with conventional DIR imaging. RESULTS: Single-slice PS-DIR
      provided effective blood-signal suppression over a wide range of inversion times,
      enhancing wall-lumen contrast and vessel wall conspicuity for carotid arteries.
      Multislice PS-DIR imaging with effective blood-signal suppression is enabled.
      CONCLUSIONS: A variant of the PS-DIR method has successfully been implemented and
      tested for carotid vessel wall imaging. This technique removes timing constraints
      related to inversion recovery, enhances wall-lumen contrast, and enables a 3-fold
      increase in volumetric coverage at no extra cost in scanning time.

PMID- 25369855
TI  - Efficient cycloaddition of epoxides and carbon dioxide over novel organic
      inorganic hybrid zeolite catalysts.
AB  - Organic-inorganic hybrid zeolites with the MFI-type lamellar structure serve as
      efficient solid Lewis base catalysts for solvent-free synthesis of a variety of
      cyclic carbonates from corresponding epoxides and carbon dioxide. The ion
      exchange with iodide, in particular, renders these materials an excellent
      catalytic activity and good recyclability. 

PMID- 25369854
TI  - Semiautomatic determination of arterial input functions for quantitative dynamic
      contrast-enhanced magnetic resonance imaging in non-small cell lung cancer
      patients.
AB  - OBJECTIVES: The aim of this study was to validate a semiautomatic detection
      method for the arterial input functions (AIFs) using Kendall coefficient of
      concordance (KCC) for quantitative analysis of dynamic contrast-enhanced magnetic
      resonance imaging in non-small cell lung cancer patients. MATERIALS AND METHODS:
      We prospectively enrolled 28 patients (17 men, 11 women; mean age, 62 years) who
      had biopsy-proven non-small cell lung cancer. All enrolled patients underwent
      dynamic contrast-enhanced magnetic resonance imaging of the entire thorax. For
      the quantitative measurement of pharmacokinetic parameters, K and ve, of the lung
      cancers, AIFs were determined in 2 different ways: a manual method that involved
      3 independent thoracic radiologists selecting a region of interest (ROI) within
      the aortic arch in the 2D coronal plane and a semiautomatic method that used in
      house software to establish a KCC score, which provided a measure of similarity
      to typical AIF pattern. Three independent readers selected voxel clusters with
      high KCC scores calculated 3-dimensionally across planes in the data set. K and
      ve were correlated using intraclass correlation coefficients (ICCs), and Bland
      Altman plots were used to examine agreement across methods and reproducibility
      within a method. RESULTS: Arterial input functions were determined using the data
      from ROI volumes that were significantly larger in the semiautomatic method (mean
      +/- SD, 3360 +/- 768 mm) than in the manual method (677 +/- 380 mm) (P < 0.001).
      K showed very strong agreement (ICC, 0.927) and ve showed moderately strong
      agreement (ICC, 0.718) between the semiautomatic and manual methods. The
      reproducibility for K (ICCmanual, 0.813 and ICCsemiautomatic, 0.998; P < 0.001)
      and ve (ICCmanual, 0.455 and ICCsemiautomatic, 0.985, P < 0.001) was
      significantly better with the semiautomatic method than the manual method.
      CONCLUSION: We found semiautomated detection using KCC to be a robust method for
      determining the AIF. This method allows for larger ROIs specified in 3D across
      planes as opposed to manually selected ROIs restricted to the 2D coronal images
      seen by the reader and provides increased reproducibility that is comparable with
      manual specification.

PMID- 25369856
TI  - Cooperative adsorption behavior of phosphopeptides on TiO2 leads to biased
      enrichment, detection and quantification.
AB  - The adsorption behavior of phosphopeptides onto TiO2 surfaces was studied using
      the quartz crystal microbalance with dissipation monitoring (QCM-D) as the main
      experimental technique. The main focus is the characterization of the emergence
      of positive cooperativity under conditions where the peptides have a positively
      charged C-term. It is shown that when carrying no net charge, small water-soluble
      peptides as a rule develop positive cooperativity. The impact of the adsorption
      mechanism on the outcome of TiO2 based enrichment methods was investigated with
      the help of matrix assisted laser desorption-ionization mass spectrometry (MALDI
      MS). The data presented illustrate how the phosphopeptide profile in the enriched
      material may deviate from that in the native sample, as cooperative
      phosphopeptides are overrepresented in the former. Furthermore, commonly employed
      washing and elution solutions may facilitate preferential release of certain
      peptides, leading to further bias in the recovered sample. Taken together, the
      results of the present study demonstrate that thorough understanding of the
      mechanisms behind the adsorption of phosphopeptides on the enrichment material is
      necessary in order to develop reliable qualitative and quantitative methods for
      phosphoproteomics. 

PMID- 25369857
TI  - Efficacy of an Internet and SMS-based integrated smoking cessation and alcohol
      intervention for smoking cessation in young people: study protocol of a two-arm
      cluster randomised controlled trial.
AB  - BACKGROUND: Tobacco smoking prevalence continues to be high, particularly among
      adolescents and young adults with lower educational levels, and is therefore a
      serious public health problem. Tobacco smoking and problem drinking often co
      occur and relapses after successful smoking cessation are often associated with
      alcohol use. This study aims at testing the efficacy of an integrated smoking
      cessation and alcohol intervention by comparing it to a smoking cessation only
      intervention for young people, delivered via the Internet and mobile phone.
      METHODS/DESIGN: A two-arm cluster-randomised controlled trial with one follow-up
      assessment after 6 months will be conducted. Participants in the integrated
      intervention group will: (1) receive individually tailored web-based feedback on
      their drinking behaviour based on age and gender norms, (2) receive individually
      tailored mobile phone text messages to promote drinking within low-risk limits
      over a 3-month period, (3) receive individually tailored mobile phone text
      messages to support smoking cessation for 3 months, and (4) be offered the option
      of registering for a more intensive program that provides strategies for smoking
      cessation centred around a self-defined quit date. Participants in the smoking
      cessation only intervention group will only receive components (3) and (4). Study
      participants will be 1350 students who smoke tobacco daily/occasionally, from
      vocational schools in Switzerland. Main outcome criteria are 7-day point
      prevalence smoking abstinence and cigarette consumption assessed at the 6-month
      follow up. DISCUSSION: This is the first study testing a fully automated
      intervention for smoking cessation that simultaneously addresses alcohol use and
      interrelations between tobacco and alcohol use. The integrated intervention can
      be easily implemented in various settings and could be used with large groups of
      young people in a cost-effective way. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN02427446 (date of registration: 08th September, 2014).

PMID- 25369859
TI  - Dual opioid therapy using methadone as a coanalgesic.

PMID- 25369860
TI  - Kinetic analysis of nitroxide radical formation under oxygenated photolysis:
      toward quantitative singlet oxygen topology.
AB  - Reaction kinetics for two sterically hindered secondary amines with singlet
      oxygen have been studied in detail. A water soluble porphyrin sensitizer,
      5,10,15,20-tetrakis-(4-sulfunatophenyl)-21,23H-porphyrin (TPPS), was irradiated
      in oxygenated aqueous solutions containing either 2,2,6,6-tetramethylpiperidin-4
      one (TMPD) or 4-[N,N,N-trimethyl-ammonium]-2,2,6,6-tetramethylpiperidinyl
      chloride (N-TMPCl). The resulting sensitization reaction produced singlet oxygen
      in high yield, ultimately leading to the formation of the corresponding nitroxide
      free radicals (R2NO) which were detected using steady-state electron paramagnetic
      resonance (EPR) spectroscopy. Careful actinometry and EPR calibration curves,
      coupled with a detailed kinetic analysis, led to a simple and compact expression
      relating the nitroxide quantum yield PhiR2NO (from the doubly-integrated EPR
      signal intensity) to the initial amine concentration [R2NH]i. With all other
      parameters held constant, a plot of PhiR2NOvs. [R2NH]i gave a straight line with
      a slope proportional to the rate constant for nitroxide formation, kR2NO. This
      establishment of a rigorous quantitative relationship between the EPR signal and
      the rate constant provides a mechanism for quantifying singlet oxygen production
      as a function of its topology in heterogeneous media. Implications for in vivo
      assessment of singlet oxygen topology are briefly discussed. 

PMID- 25369861
TI  - Single-shot laser treatment provides quasi-three-dimensional paper-based
      substrates for SERS with attomolar sensitivity.
AB  - In this study, an eco-friendly and ultrasensitive paper substrate is developed
      for surface-enhanced Raman scattering (SERS) with performance approaching single
      molecule detection. By exploiting the laser-induced photothermal effect, paper
      fibrils with hybrid micro- and nanostructures can facilitate the formation of
      highly dense metal nanoparticles (NPs) after a single shot of laser illumination.
      Metal films deposited on the paper substrates feature discontinuous morphologies,
      with the fragments acting as multiple nucleation sites. Because thermal
      conductivity is low on the broken films and the underlying paper fibrils, the
      incident energy is absorbed efficiently. Moreover, the quasi-three-dimensional
      distribution of NPs on the SERS paper greatly enhances the SERS signals within
      the effective collection volume of a Raman microscope. As a result of the large
      number of highly effective hot spots and the condensation effect, the hydrophobic
      SERS paper provides SERS signals with stable and uniform reproducibility
      throughout the detection area. The limits of detection when using the paper
      substrates reach the attomolar (10(-18) M) level, thereby approaching single
      molecule detection.

PMID- 25369864
TI  - Energy transfer between eigenmodes in multimodal atomic force microscopy.
AB  - We present experimental and computational investigations of tetramodal and
      pentamodal atomic force microscopy (AFM), respectively, whereby the first four or
      five flexural eigenmodes of the cantilever are simultaneously excited externally.
      This leads to six to eight additional observables in the form of amplitude and
      phase signals, with respect to the monomodal amplitude modulation method. We
      convert these additional observables into three or four dissipation and virial
      expressions, and show that these quantities can provide enhanced contrast that
      would otherwise remain hidden in the original observables. We also show that the
      complexity of the multimodal impact leads to significant energy transfer between
      the active eigenmodes, such that the dissipated power for individual eigenmodes
      may be positive or negative, while the total dissipated power remains positive.
      These results suggest that the contrast of individual eigenmodes in
      multifrequency AFM should be not be considered in isolation and that it may be
      possible to use different eigenfrequencies to probe sample properties that
      respond to different relaxation times. 

PMID- 25369862
TI  - Biomolecule-mediated CdS-TiO2-reduced graphene oxide ternary nanocomposites for
      efficient visible light-driven photocatalysis.
AB  - We report an environmentally friendly synthetic strategy to fabricate reduced
      graphene oxide (rGO)-based ternary nanocomposites, in which glutathione (GSH)
      acts both as a reducing agent for graphene oxide and sulfur donor for CdS
      synthesis under modified hydrothermal (MHT) conditions. The report becomes
      interesting as pH variation evolves two distinctly different semiconducting
      nanocrystals of anatase/rutile TiO2 and hexagonal yellow/cubic red CdS, and their
      packaging makes them suitable photocatalysts for dye degradation. Herein, a
      titanium peroxo compound, obtained from commercial TiO2, is hydrolyzed to TiO2
      nanostructures without any additives. The yellow colored CdS-TiO2-rGO (YCTG), one
      of the ternary photocatalysts, shows maximum efficiency compared to the
      corresponding red ternary CdS-TiO2-rGO or binary photocatalysts (CdS-rGO, TiO2
      rGO and CdS-TiO2) for dye degradation under visible light irradiation. Systematic
      characterizations reveal that TiO2 presents at the interface of rGO and CdS in
      YCTG and thus makes a barrier that inhibits the direct interaction between rGO
      and CdS. This leads to a relatively higher bandgap value for CdS in YCTG (2.15 eV
      vs. 2.04 eV for CdS-rGO) but with better photocatalytic activity simply by
      diminishing the possibility of the charge-recombination process. In the present
      situation, rGO in the YCTG also supports faster dye degradation through higher
      dye adsorption and rapid internal electron transfer (CdS->TiO2->rGO) in the YCTG
      nanocomposite. Thus, a simple aqueous phase and a greener synthetic procedure
      results in a low-cost, highly effective visible light-responsive material for
      environmental application. 

PMID- 25369863
TI  - MALAT1 long non-coding RNA is overexpressed in multiple myeloma and may serve as
      a marker to predict disease progression.
AB  - BACKGROUND: The pathogenesis of multiple myeloma involves complex genetic and
      epigenetic events. This study aimed to investigate the role and clinical
      relevance of the long non-coding RNA (lncRNA), metastasis-associated lung
      adenocarcinoma transcript 1 (MALAT1) in multiple myeloma. METHODS: Bone marrow
      mononuclear cells were collected for analysis. The samples of multiple myeloma
      were taken from 45 patients at diagnosis, 61 post-treatment, and 18 who relapsed
      or had progression. Control samples were collected from 20 healthy individuals.
      Real-time quantitative reverse transcription polymerase chain reactions were
      performed to evaluate the expression of MALAT1. The clinical relevance of MALAT1
      expression was also explored. RESULTS: MALAT1 was overexpressed in the newly
      diagnosed patients compared with post-treatment patients (mean ?CT: -5.54 +/-
      0.16 vs. -3.84 +/- 0.09, 3.25-fold change; p < 0.001) and healthy individuals
      (mean ?CT: -5.54 +/- 0.16 vs. -3.95 +/- 0.21, 3.01-fold change; p < 0.001). The
      expression of MALAT1 strongly correlated with disease status, and the magnitude
      of change in MALAT1 post-treatment had prognostic relevance. The patients with
      early progression had a significantly smaller change in MALAT1 after treatment
      (mean ?CT change: 1.26 +/- 1.06 vs. 2.09 +/- 0.79, p = 0.011). A cut-off value of
      the change in MALAT1 (?CT change: 1.5) was obtained, and the patients with a
      greater decrease in MALAT1 (difference in ?CT >1.5) had significantly longer
      progression-free survival compared with the patients with a smaller MALAT1 change
      (24 months vs. 11 months; p = 0.001). For the post-treatment patients, the risk
      of early progression could be predicted using this cut-off value. CONCLUSIONS:
      MALAT1 was overexpressed in patients with myeloma and may play a role in its
      pathogenesis. In addition, MALAT1 may serve as a molecular predictor of early
      progression.

PMID- 25369865
TI  - No antibiotics in acute uncomplicated diverticulitis: does it work?
AB  - BACKGROUND: The first randomized multicenter study evaluating the need for
      antibiotic treatment in patients with acute uncomplicated diverticulitis (AUD)
      could not demonstrate any benefit gained from antibiotic use. The aim of this
      study was to review the application of the no antibiotic policy and its
      consequences in regard to complications and recurrence. METHODS: This
      retrospective population-based cohort study included all patients diagnosed with
      all types of colonic diverticulitis during the year 2011 at Vastmanland Hospital
      Vasteras, Sweden. All medical records were carefully reviewed. Primary outcomes
      were the types of treatment adopted for diverticulitis, complications and
      recurrence. RESULTS: In total, 246 patients with computer tomography-verified
      diverticulitis were identified, 195 with primary AUD and 51 with acute
      complicated diverticulitis. Age, sex, and temperature at admission were similar
      between the groups but there was a significant difference in white blood cell
      count, C-reactive protein, and length of hospital stay. In the AUD group, 178
      (91.3%) patients were not treated with antibiotics. In this group, there were six
      (3.4%) readmissions but only two developed an abscess. Of the remaining 17
      patients (8.7%) who were treated with antibiotics in the AUD group, one developed
      an abscess. Twenty-five (12.8%) patients in the AUD group presented with a
      recurrence within 1 year. CONCLUSION: The no-antibiotic policy for AUD is safe
      and applicable in clinical practice. The previous results of a low complication
      and recurrence rate in AUD are confirmed. There is no need for antibiotic
      treatment for AUD. What does this paper add to the literature? Despite published
      papers with excellent results, there are still doubts about patient safety
      against the policy to not use antibiotics in acute uncomplicated diverticulitis.
      This is the first paper, in actual clinical practice, to confirm that the no
      antibiotic policy for acute uncomplicated diverticulitis is applicable and safe.

PMID- 25369866
TI  - Smart sustainable bottle (SSB) system for E. coli based recombinant protein
      production.
AB  - BACKGROUND: Recombinant proteins are usually required in laboratories interested
      in the protein but not in the production process itself. Thus, technical
      equipment which is easy to handle and straight forward protein production
      procedures are of great benefit to those laboratories. Companies selling single
      use cultivation bags and bioreactors are trying to satisfy at least part of these
      needs. However, single-use systems can contribute to major costs which might be
      acceptable when "good manufacturing practices" are required but not acceptable
      for most laboratories facing tight funding. RESULTS: The assembly and application
      of a simple self-made "smart sustainable bottle" (SSB) system for E. coli based
      protein production is presented. The core of the SSB system is a 2-L glass bottle
      which is operated at constant temperature, air flow, and stirrer speed without
      measurement and control of pH and dissolved oxygen. Oxygen transfer capacities
      are in the range as in conventional bioreactors operated at intermediate aeration
      rates and by far exceed those found in conventional shaking flasks and disposable
      bioreactors. The SSB system was applied for the production of various recombinant
      proteins using T7-based expression systems and a defined autoinduction medium.
      The production performance regarding amount and solubility of proteins with
      robust and delicate properties was as good as in state-of-the-art stirred tank
      commercial bioreactors. CONCLUSIONS: The SSB system represents a low cost protein
      production device applicable for easy, effective, and reproducible recombinant
      protein production.

PMID- 25369867
TI  - Quantitative proteomic analysis of Down syndrome in the umbilical cord blood
      using iTRAQ.
AB  - Down sydrome (DS) is a relatively frequent chromosomal disorder, which has no
      safe and effective method of prenatal diagnosis to date. The present study was
      designed to identify DS biomarkers. We quantified the changes in the umbilical
      cord blood protein levels between DS-affected and healthy (control) pregnant
      females using isobaric tags for relative and absolute quantification (iTRAQ) and
      Gene Ontology (GO) analysis. A total of 505 proteins were identified, and of
      these, five proteins showed significantly different concentrations between the DS
      and the control group. These proteins may thus be relevant to DS and constitute
      potential DS biomarkers. 

PMID- 25369868
TI  - Peer reviewers.

PMID- 25369869
TI  - Effects of epidural neostigmine and clonidine in labor analgesia: a systematic
      review and meta-analysis.
AB  - AIM: To evaluate the effect and quality of epidural neostigmine and clonidine
      added to initial spinal analgesia in labor analgesia. METHODS: A systematic
      search was conducted in the Medline, Embase, Cochrane Library and China National
      Knowledge Infrastructure electronic databases. Case-control studies reporting
      epidural administration of neostigmine and clonidine for labor analgesia were
      retrieved. For continuous variables, mean differences (MD) and 95% confidence
      intervals (CI) were calculated; for binary classification variables, odds ratio
      (OR) and risk ratios (RR) with their 95% CI were analyzed. RESULTS: A total of
      four case-control studies, including 280 parturients, were identified in this
      meta-analysis. The results showed that epidural clonidine and neostigmine
      significantly prolonged initial analgesia (MD = 37.79, 95% CI = 9.37-66.21, P =
      0.0.009) and reduced hourly local anesthetics and opioid administration (MD = 
      5.49, 95% CI = -6.78, -4.21, P < 0.0001). There was no significant difference in
      total duration of labor, mode of delivery (cesarean section rate or instrumental
      delivery rate) and Apgar scores of the neonates in the two groups. CONCLUSION:
      Epidural administration of neostigmine and clonidine, following the spinal
      injection of local anesthetic, has a stronger analgesic effect in managing labor
      pain and reduces hourly anesthetic consumption. No obvious adverse reactions were
      found.

PMID- 25369870
TI  - Identification of optimal reference genes for quantitative PCR studies on human
      mesenchymal stem cells.
AB  - Quantitative polymerase chain reaction (qPCR) analysis is a commonly used method
      for the study of mRNA expression throughout the field of mesenchymal stem cell
      (MSC) research. This technology is simple and sensitive; however the results may
      vary significantly due to the use of various reference genes (RGs) as
      normalizers. Therefore, the reliable use of RGs is vital for obtaining accurate
      results. The present study focuses on ten putative RGs for the normalization of
      qPCR data between human bone marrow-derived MSCs (BM-MSCs) and fetal tissue
      derived MSCs (FT-MSCs). The total RNA from these two types of MSC was isolated
      using TRIzol reagent. cDNA was generated from the RNA via reverse transcription
      and subsequently analyzed by qPCR using ten common RGs as normalizers. These RGs
      included 18S, ACTB, B2M, HPRT1, GAPDH, TBP, PPIA, RPLP0, PGK1 and RPL13A. GeNorm,
      NormFinder and BestKeeper software were used to analyze the qPCR results by
      evaluating the expression stabilities of the ten candidate RGs in BM-MSCs and FT
      MSCs. Consequently, several of the commonly used RGs, including 18S, ACTB and
      TBP, were demonstrated to be unsuitable for normalization in these two MSCs,
      whereas RPL13A, B2M and PPIA were the most stable RGs and were therefore reliable
      for use in qPCR studies. Combining multiple RGs had no contribution towards
      increasing their stabilities. In conclusion, the present study revealed that
      RPL13A, B2M and PPIA were the optimal RGs for qPCR studies comparing BM-MSCs and
      FT-MSCs. 

PMID- 25369871
TI  - Extensive transcriptional response associated with seasonal plasticity of
      butterfly wing patterns.
AB  - In the eastern United States, the buckeye butterfly, Junonia coenia, shows
      seasonal wing colour plasticity where adults emerging in the spring are tan,
      while those emerging in the autumn are dark red. This variation can be
      artificially induced in laboratory colonies, thus making J. coenia a useful model
      system to examine the mechanistic basis of plasticity. To better understand the
      developmental basis of seasonal plasticity, we used RNA-seq to quantify
      transcription profiles associated with development of alternative seasonal wing
      morphs. Depending on the developmental stage, between 547 and 1420 transfrags
      were significantly differentially expressed between morphs. These extensive
      differences in gene expression stand in contrast to the much smaller numbers of
      differentially expressed transcripts identified in previous studies of genetic
      wing pattern variation in other species and suggest that environmentally induced
      phenotypic shifts arise from very broad systemic processes. Analyses of candidate
      endocrine and pigmentation transcripts revealed notable genes upregulated in the
      red morph, including several ecdysone-associated genes, and cinnabar, an
      ommochrome pigmentation gene implicated in colour pattern variation in other
      butterflies. We also found multiple melanin-related transcripts strongly
      upregulated in the red morph, including tan and yellow-family genes, leading us
      to speculate that dark red pigmentation in autumn J. coenia may involve
      nonommochrome pigments. While we identified several endocrine and pigmentation
      genes as obvious candidates for seasonal colour morph differentiation, we
      speculate that the majority of observed expression differences were due to
      thermal stress response. The buckeye transcriptome provides a basis for further
      developmental studies of phenotypic plasticity.

PMID- 25369872
TI  - Statin discontinuation in nursing home residents with advanced dementia.
AB  - OBJECTIVES: To describe patterns of, and factors associated with, statin use and
      discontinuation in nursing home (NH) residents progressing to advanced dementia
      and followed for at least 90 days. DESIGN: Retrospective inception cohort using a
      dataset linking 2007 to 2008 Minimum Data Set (MDS) to Medicare denominator and
      Part D files. SETTING: All NHs in five states (Minnesota, Massachusetts,
      Pennsylvania, California, Florida). PARTICIPANTS: NH residents with dementia.
      MEASUREMENTS: Residents who developed advanced dementia were observed from
      baseline (date of progression to very severe cognitive impairment with eating
      problems) and followed for at least 90 days to statin discontinuation or death.
      Logistic regression was used to identify baseline factors associated with statin
      use. Cox proportional hazard regression was used to identify factors associated
      with time to statin discontinuation. RESULTS: Of 10,212 residents, 16.6% (n =
      1,699) used statins. Greater odds of statin use were associated with having
      diabetes mellitus (adjusted odds ratio (AOR) = 1.24, 95% confidence interval (CI)
      = 1.09-1.40), stroke (AOR = 1.31, 95% CI = 1.16-1.48), and hypertension (AOR =
      1.35, 95% CI = 1.18-1.54); hospice enrollment was associated with lower odds (AOR
      = 0.75, 95% CI = 0.64-0.89). In follow-up, 37.2% (n = 632) discontinued statins.
      Median time to discontinuation was 36 days (interquartile range 12-110 days).
      Shorter time to discontinuation was associated with hospitalization in past 30
      days (adjusted hazard ratio (AHR) = 1.67, 95% CI = 1.40-1.99) and more daily
      medications (AHR = 1.02, 95% CI = 1.01-1.04). When statins were discontinued,
      15.0% (n = 95) of residents stopped only statins, and 47.5% (n = 300) stopped at
      least one other medication. CONCLUSION: Most NH residents who use statins at the
      time of progression to advanced dementia continue use in follow-up.

PMID- 25369874
TI  - Caring for early-onset dementia with excessive wandering of over 30 kilometres
      per day: a case report.
AB  - Excessive wandering in people in dementia is associated with a severe care
      burden. However, the quantification of excessive wandering has not been
      described, and its cause and treatment have not been evaluated with objective
      measurements to date. The purpose of this study was to evaluate pharmacological
      treatments and non-pharmacological interventions to reduce excessive wandering in
      an early-onset Alzheimer disease patient with objective indicators. Wandering was
      quantified using an integrated circuit monitoring system that measured the
      distance moved and the location of the patient. Monitoring was conducted in the
      dementia ward of a general hospital in 2012. Sleep quality was measured by non
      wear actigraphy. The study was approved by the ethics committees of the Osaka
      University School of Allied Health Science, and of the study hospital. The case
      involved a 62-year-old woman diagnosed with early-onset Alzheimer disease and
      hospitalized in 2012 because of irritability and agitation; her Mini-Mental State
      Examination score was 5/30 and her Clinical Dementia Rating score was 3. When
      olanzapine (2.5 mg) was prescribed, she developed insomnia, and her wandering
      movements increased from 10 to 20 km/day. On some days, it exceeded 30 km/day,
      and she walked most of the night. She did not experience weight loss or physical
      exhaustion, but she sustained a minor injury in her left sole. Olanzapine was
      increased to 7.5 mg, but these problems persisted. Nursing staff discovered
      triggers for wandering and insomnia, including high sensitivity to odour and
      noise in the living room or her room. When the environment was changed to meet
      her needs, the distance moved per day decreased to <15 km and the sleep
      disturbances disappeared. This case demonstrated the difficulty in assessing the
      degree of ambulation and sleep disorder. Objective indicators are essential in
      evaluating the effectiveness of pharmacological and non-pharmacological
      interventions. 

PMID- 25369873
TI  - Structure and functional characterization of pyruvate decarboxylase from
      Gluconacetobacter diazotrophicus.
AB  - BACKGROUND: Bacterial pyruvate decarboxylases (PDC) are rare. Their role in
      ethanol production and in bacterially mediated ethanologenic processes has,
      however, ensured a continued and growing interest. PDCs from Zymomonas mobilis
      (ZmPDC), Zymobacter palmae (ZpPDC) and Sarcina ventriculi (SvPDC) have been
      characterized and ZmPDC has been produced successfully in a range of heterologous
      hosts. PDCs from the Acetobacteraceae and their role in metabolism have not been
      characterized to the same extent. Examples include Gluconobacter oxydans (GoPDC),
      G. diazotrophicus (GdPDC) and Acetobacter pasteutrianus (ApPDC). All of these
      organisms are of commercial importance. RESULTS: This study reports the kinetic
      characterization and the crystal structure of a PDC from Gluconacetobacter
      diazotrophicus (GdPDC). Enzyme kinetic analysis indicates a high affinity for
      pyruvate (K M 0.06 mM at pH 5), high catalytic efficiencies (1.3 * 10(6) M(-1) *
      s(-1) at pH 5), pHopt of 5.5 and Topt at 45 degrees C. The enzyme is not
      thermostable (T1/2 of 18 minutes at 60 degrees C) and the calculated number of
      bonds between monomers and dimers do not give clear indications for the
      relatively lower thermostability compared to other PDCs. The structure is highly
      similar to those described for Z. mobilis (ZmPDC) and A. pasteurianus PDC (ApPDC)
      with a rmsd value of 0.57 A for Calpha when comparing GdPDC to that of ApPDC.
      Indole-3-pyruvate does not serve as a substrate for the enzyme. Structural
      differences occur in two loci, involving the regions Thr341 to Thr352 and Asn499
      to Asp503. CONCLUSIONS: This is the first study of the PDC from G. diazotrophicus
      (PAL5) and lays the groundwork for future research into its role in this
      endosymbiont. The crystal structure of GdPDC indicates the enzyme to be
      evolutionarily closely related to homologues from Z. mobilis and A. pasteurianus
      and suggests strong selective pressure to keep the enzyme characteristics in a
      narrow range. The pH optimum together with reduced thermostability likely reflect
      the host organisms niche and conditions under which these properties have been
      naturally selected for. The lack of activity on indole-3-pyruvate excludes this
      decarboxylase as the enzyme responsible for indole acetic acid production in G.
      diazotrophicus.

PMID- 25369875
TI  - Assessment of the hemodynamic profile in periodontal tissues of diabetic subjects
      with periodontitis by optical spectroscopy.
AB  - BACKGROUND AND OBJECTIVE: The influence of diabetes mellitus (DM) on the
      hemodynamics of periodontal tissues has not been assessed previously. The primary
      objective of this study was to validate optical spectroscopy as a periodontal
      diagnostic tool for subjects with type 2 DM and chronic periodontitis. MATERIAL
      AND METHODS: Using a portable optical near-infrared spectrometer, optical spectra
      were obtained from healthy (n = 127), gingivitis (n = 115), and periodontitis (n
      = 109) sites of 65 subjects with type 2 DM and chronic periodontitis. Healthy (n
      = 65) sites of 15 nondiabetic subjects without periodontitis were used as
      controls. A modified Beer-Lambert unmixing model that incorporates a
      nonparametric scattering-loss function was used to determine the relative
      contribution of deoxygenated hemoglobin and oxygenated hemoglobin (HbO2 ) to the
      overall spectrum. The balance between tissue oxygen delivery and oxygen
      utilization in periodontal tissues was assessed. RESULTS: In diabetic subjects,
      tissue oxygen saturation and HbO2 concentration were significantly decreased in
      the periodontitis sites (p < 0.01) compared with the healthy and gingivitis
      sites. Furthermore, tissue oxygenation in healthy sites of control subjects was
      significantly higher than that in sites of diabetic subjects (p < 0.01).
      CONCLUSION: In summary, the results of this study suggest that optical
      spectroscopy can monitor the hemodynamic profile in diabetic subjects with
      chronic periodontitis. Furthermore, healthy sites of diabetic subjects presented
      lower tissue oxygenation than did those of nondiabetic subjects.

PMID- 25369876
TI  - Intrarenal bradykinin elicits reno-renal reflex sympatho-excitation and renal
      nerve-dependent fluid retention.
AB  - AIMS: The renal sensory nerves are importantly involved in the sympathetic
      regulation of cardiovascular and renal function. Two reno-renal reflexes are
      recognized, one in which activation of renal sensory nerves elicits a renal
      sympatho-inhibition, and one which causes a renal sympatho-excitation and about
      which little is known. This study investigated the role of bradykinin (BK) in
      engaging an excitatory reno-renal reflex. METHODS: Rats were anaesthetized
      (chloralose/urethane) and prepared for the measurement of renal function or renal
      sympathetic nerve activity (RSNA). BK was infused into the cortico-medullary
      border of the ipsilateral kidney and the impact on contralateral renal function
      and RSNA evaluated. RESULTS: Intrarenal infusion of BK at 3 * 10(-9) and 6 * 10(
      9) g L(-1) had no effect on mean arterial pressure, at 104 +/- 5 mmHg or
      glomerular filtration rate in either the ipsilateral or contralateral kidneys, at
      4.31 +/- 0.45 mL min(-1) kg(-1) . At the highest dose of BK, fractional sodium
      excretion (FENa) was 1.47% in the ipsilateral kidney and was significantly lower,
      at 0.64% (P < 0.05) in the contralateral kidney but this difference did not occur
      following ipsilateral renal denervation. Ipsilateral intrarenal infusion of BK at
      3 * 10(-9) , 6 * 10(-9) and 1.2 * 10(-8) g L(-1) elicited dose-related increases
      (P < 0.05) in contralateral RSNA, reaching some 78% at the highest dose, but
      these responses were prevented by ipsilateral renal denervation. CONCLUSIONS:
      Intrarenal infusion of BK produced an excitatory reno-renal reflex which was
      expressed as a renal nerve-dependent antinatriuresis in the contralateral kidney.
      The findings suggest that inflammatory mediators such as BK may be important in
      initiating a sympatho-excitation associated with renal and cardiovascular
      diseases.

PMID- 25369877
TI  - Central venous catheter-related thrombosis and thromboprophylaxis in children: a
      systematic review and meta-analysis: reply.

PMID- 25369878
TI  - Correlation of trends in cashmere production and declines of large wild mammals:
      response to Berger et al. 2013.

PMID- 25369879
TI  - Novel method for the management of stenosis after gastric endoscopic submucosal
      dissection: mucosal incision with steroid injection contralateral to the severely
      contracted scar.
AB  - The aim of the present report was to investigate the efficacy of local steroid
      injection and oral administration contralateral to a severe contracted scar of
      large endoscopic submucosal dissection (ESD) for gastric cancer. Among 254 cases
      that underwent gastric ESD, seven patients underwent resection of more than three
      quarters of the circumference of the stomach. Two patients were excluded because
      they did not meet curative resection criteria of Japan Gastroenterological
      Endoscopy Society. Therefore, in five patients, circumferentiality, symptom
      appearance period, and weight loss period were examined. Effect of a
      contralateral normal mucosa incision for releasing the stenosis followed by local
      injection and oral steroids were also examined. Abdominal bloating, vomiting, and
      loss of appetite appeared 42 days on average after gastric ESD, whereas weight
      loss >5 kg was observed an average of 52.6 days after gastric ESD. Average
      contralateral mucosal incision length was 51 mm, whereas the average mucosal
      incision width was 31 mm. All patients underwent a mucosal incision and were
      given a local injection of 100 mg triamcinolone acetonide. Two patients received
      an additional 20 mg oral steroid. In cases combined with oral steroid, there was
      no re-stenosis after the mucosal incision, but two to three balloon dilatations
      were necessary in three cases in which oral steroids were not given. This method
      is considered useful for stenosis after large ESD for gastric cancer. 

PMID- 25369880
TI  - Occupational anaphylaxis--an EAACI task force consensus statement.
AB  - Anaphylaxis is a systemic allergic reaction, potentially life-threatening that
      can be due to nonoccupational or, less commonly, to occupational triggers.
      Occupational anaphylaxis (OcAn) could be defined as anaphylaxis arising out of
      triggers and conditions attributable to a particular work environment.
      Hymenoptera stings and natural rubber latex are the commonest triggers of OcAn.
      Other triggers include food, medications, insect/mammal/snake bites, and
      chemicals. The underlying mechanisms of anaphylactic reactions due to
      occupational exposure are usually IgE-mediated and less frequently non-IgE
      mediated allergy or nonallergic. Some aspects of work-related allergen exposure,
      such as route and frequency of exposure, type of allergens, and cofactors may
      explain the variability of symptoms in contrast to the nonoccupational setting.
      When assessing OcAn, both confirmation of the diagnosis of anaphylactic reaction
      and identification of the trigger are required. Prevention of further episodes is
      important and is based on removal from further exposure. Workers with a history
      of OcAn should immediately be provided with a written emergency management plan
      and an adrenaline auto-injector and educated to its use. Immunotherapy is
      recommended only for OcAn due to Hymenoptera stings. 

PMID- 25369881
TI  - Doping in sport: effects, harm and misconceptions.
AB  - Doping in sport is a widespread problem not just among elite athletes, but even
      more so in recreational sports. In scientific literature, major emphasis is
      placed on doping detection, whereas detrimental effects of doping agents on
      athletes' health are seldom discussed. Androgenic anabolic steroids are well
      known for their positive effects on muscle mass and strength. Human growth
      hormone also increases muscle mass, although the majority of that is an increase
      in extracellular fluid and not the functional muscle mass. In recreational
      athletes, growth hormone does not have major effect on muscle strength, power or
      aerobic capacity, but stimulates anaerobic exercise capacity. Erythropoietin
      administration increases oxygen-carrying capacity of blood improving endurance
      measures, whereas systemic administration of beta-adrenergic agonists may have
      positive effect on sprint capacity, and beta-adrenergic antagonists reduce muscle
      tremor. Thus, there are certain drugs that can improve selective aspects of
      physical performance. However, most of the doping agents exert serious side
      effects, especially when used in combination, at high doses and for a long
      duration. The extent of long-term health consequences is difficult to predict,
      but likely to be substantial, especially when gene doping is considered. This
      review summarises the main groups of doping agents used by athletes, with the
      main focus on their effects on athletic performance and adverse effects. 

PMID- 25369882
TI  - Ligand-induced compaction of the PEX5 receptor-binding cavity impacts protein
      import efficiency into peroxisomes.
AB  - Peroxisomes entirely rely on the import of their proteome across the peroxisomal
      membrane. Recognition efficiencies of peroxisomal proteins vary by more than 1000
      fold, but the molecular rationale behind their subsequent differential import and
      sorting has remained enigmatic. Using the protein cargo alanine-glyoxylate
      aminotransferase as a model, an unexpected increase from 34 to 80% in peroxisomal
      import efficiency of a single-residue mutant has been discovered. By high
      resolution structural analysis, we found that it is the recognition receptor PEX5
      that adapts its conformation for high-affinity binding rather than the cargo
      protein signal motif as previously thought. During receptor recognition, the
      binding cavity of the receptor shrinks to one third of its original volume. This
      process is impeded in the wild-type protein cargo because of a bulky side chain
      within the recognition motif, which blocks contraction of the PEX5 binding
      cavity. Our data provide a new insight into direct protein import efficiency by
      removal rather than by addition of an apparent specific sequence signature that
      is generally applicable to peroxisomal matrix proteins and to other receptor
      recognition processes. 

PMID- 25369883
TI  - Horizontal Gene Transfer and Its Part in the Reorganisation of Genetics during
      the LUCA Epoch.
AB  - Currently there are five known mechanisms of horizontal gene transfer (HGT):
      transduction, conjugation, transformation, gene transfer agents and membrane
      vesicle transfer. The question here is: what part did HGT play in the
      reorganisation of genetics during the last universal common ancestor (LUCA)
      epoch? LUCA is a construct to explain the origin of the three domains of life;
      namely Archaea, Bacteria and Eukarya. This editorial offers a general
      introduction to the relevance and ultimate significance of HGT in relation to the
      LUCA. [...]. 

PMID- 25369884
TI  - Distance and Size Perception in Astronauts during Long-Duration Spaceflight.
AB  - Exposure to microgravity during spaceflight is known to elicit orientation
      illusions, errors in sensory localization, postural imbalance, changes in
      vestibulo-spinal and vestibulo-ocular reflexes, and space motion sickness. The
      objective of this experiment was to investigate whether an alteration in
      cognitive visual-spatial processing, such as the perception of distance and size
      of objects, is also taking place during prolonged exposure to microgravity. Our
      results show that astronauts on board the International Space Station exhibit
      biases in the perception of their environment. Objects' heights and depths were
      perceived as taller and shallower, respectively, and distances were generally
      underestimated in orbit compared to Earth. These changes may occur because the
      perspective cues for depth are less salient in microgravity or the eye-height
      scaling of size is different when an observer is not standing on the ground. This
      finding has operational implications for human space exploration missions. 

PMID- 25369885
TI  - Simulations of Prebiotic Chemistry under Post-Impact Conditions on Titan.
AB  - The problem of how life began can be considered as a matter of basic chemistry.
      How did the molecules of life arise from non-biological chemistry? Stanley
      Miller's famous experiment in 1953, in which he produced amino acids under
      simulated early Earth conditions, was a huge leap forward in our understanding of
      this problem. Our research first simulated early Earth conditions based on
      Miller's experiment and we then repeated the experiment using Titan post-impact
      conditions. We simulated conditions that could have existed on Titan after an
      asteroid strike. Specifically, we simulated conditions after a potential strike
      in the subpolar regions of Titan that exhibit vast methane-ethane lakes. If the
      asteroid or comet was of sufficient size, it would also puncture the icy crust
      and bring up some of the subsurface liquid ammonia-water mixture. Since, O'Brian,
      Lorenz and Lunine showed that a liquid water-ammonia body could exist between
      about 102-104 years on Titan after an asteroid impact we modified our
      experimental conditions to include an ammonia-water mixture in the reaction
      medium. Here we report on the resulting amino acids found using the Titan post
      impact conditions in a classical Miller experimental reaction set-up and how they
      differ from the simulated early Earth conditions. 

PMID- 25369887
TI  - True durability: HIV virologic suppression in an urban clinic and implications
      for timing of intensive adherence efforts and viral load monitoring.
AB  - Although the majority of HIV-infected patients who begin potent antiretroviral
      therapy should expect long-term virologic suppression, the realities in practice
      are less certain. Durability of viral suppression was examined to define the best
      timing of targeted adherence strategies and intensive viral load monitoring in an
      urban clinic population with multiple challenges to ART adherence. We examined
      the risk of viral rebound for patients who achieved two consecutive viral loads
      lower than the lower limit of quantification (LLOQ) within 390 days. For 791
      patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first
      viral load was 36.9 % (95 % CI 32.2-41.6) in the first year, 26.9 % (95 % CI 21.7
      32.1) in the year following one year of viral suppression, and 24.6 % (95 % CI
      18.4-30.9) in the year following 2 years of viral suppression. However, for
      patients with CD4 >=300 cells/ul who had 3-6 years of virologic suppression, the
      risk of viral rebound was very low. At the population level, the risk of viral
      rebound in a complex urban clinic population is surprisingly high even out to 3
      years. Intensified monitoring and adherence efforts should target this high risk
      period. Thereafter, confidence in truly durable virologic suppression is
      improved. 

PMID- 25369888
TI  - Inconsistencies on U.S. Departments of Health Websites Regarding Anal Use of the
      Female Condom.
AB  - The female condom (FC) is FDA approved to prevent pregnancy and sexually
      transmitted infections during vaginal intercourse, but not for use during anal
      intercourse. Studies suggest that a sizeable proportion of men who have sex with
      men use the FC for anal intercourse despite lack of safety and efficacy
      information. We reviewed Department of Health (DOH) websites for U.S. states (n =
      50) and major municipalities (population >500,000; n = 29) regarding anal use of
      the FC. Forty-eight (60.8 %) websites mentioned the FC, of which only 21 (45.8 %)
      mentioned anal use. Of those that mention anal use, 8 (38.1 %) supported, 13
      (61.9 %) were neutral, and 1 (4.8 %) discouraged this use. Ten websites (47.6 %)
      provided instructions for anal use of the FC-ranging from removal of the inner
      ring, leaving the inner ring in place, and either option. In the absence of
      safety and efficacy data, U.S. DOH websites are providing different and often
      contradictory messages about the FC for anal sex. 

PMID- 25369889
TI  - Acute and chronic Staphylococcus epidermidis post-operative endophthalmitis: The
      importance of biofilm production.
AB  - To report two cases of acute and chronic-onset, postoperative Staphylococcus
      epidermidis endophthalmitis and discuss the virulence and treatment of this
      saprophytic pathogen. After clinical diagnosis of endophthalmitis, prompt
      vitreous culture was performed with injection of intravitreal vancomycin 1 mg/0.1
      mL and ceftazidime 2.25 mg/0.1 mL. With no improvement after this procedure, a
      pars plana vitrectomy and lensectomy were performed to further decrease microbial
      load and repeat the intravitreal antibiotic. The lens and large amounts of
      fibrotic tissue were removed, and the posterior capsule was stripped. Vitreous
      cultures grew S. epidermidis sensitive to vancomycin. Intraoperative findings
      included dense vitreous opacification with extensive vitreous bands and pus
      extending into the zonules. During the removal of the IOL, adherent pus filaments
      were removed; however, only a moderate amount of bacteria was detected on the
      IOL. Further intravitreal vancomycin (1 mg/0.1 mL) and ceftazidime (2.25 mg/0.1
      mL) were injected. Staphylococcus epidermidis is widely reported as responsible
      for medical device-related sepsis. This is mainly due to the production of slime,
      an exopolysaccharide that eventually leads to the formation of biofilm, one of
      the most important virulence factors. The failure of intravitreal antibiotic
      treatment in our two biofilm-associated infections may be due to the considerable
      amount of slime and pus found extending into the zonules and adherent to the IOL
      during surgery.

PMID- 25369890
TI  - Calcifediol versus vitamin D3 effects on gait speed and trunk sway in young
      postmenopausal women: a double-blind randomized controlled trial.
AB  - In this double-blind RCT, 4-month treatment with calcifediol compared with
      vitamin D3 improved gait speed by 18% among young postmenopausal women.
      Consistently, change in 25(OH)D blood levels over time were significantly
      correlated with improvement in gait speed in these women. No effect could be
      demonstrated for trunk sway. INTRODUCTION: The aim of this study is to test the
      effect of calcifediol compared with vitamin D3 on gait speed and trunk sway.
      METHODS: Twenty healthy postmenopausal women with an average 25(OH)D level of
      13.2 ng/ml (SD = +/-3.9) and a mean age of 61.5 years (SD = +/-7.2) were
      randomized to either 20 MUg of calcifediol or 20 MUg (800 IU) of vitamin D3 per
      day in a double-blind manner. At baseline and at 4 months of follow-up, the same
      physiotherapist blinded to treatment allocation tested 8-m gait speed and a body
      sway test battery (Sway star pitch and roll angle plus velocity while walking 8
      m, and standing on both legs on a hard and soft surface). All analyses adjusted
      for baseline measurement, age, and body mass index. RESULTS: Mean 25(OH)D levels
      increased to 69.3 ng/ml (SD = +/-9.5) in the calcifediol group and to 30.5 ng/ml
      (SD = +/-5.0) in the vitamin D3 group (p < 0.0001). Women receiving calcifediol
      compared with vitamin D3 had an 18% greater improvement in gait speed at 4-month
      follow-up (p = 0.046) adjusting for baseline gait speed, age, and body mass
      index. Also, change in gait speed was significantly correlated with change in
      serum 25(OH)D concentrations (r = 0.5; p = 0.04). Across three tests of trunk
      sway, there were no consistent differences between groups and no significant
      correlation between change in 25(OH)D serum concentrations and change in trunk
      sway. CONCLUSIONS: Calcifediol improved gait speed in early postmenopausal women
      compared with vitamin D3 and change in 25(OH)D level was moderately correlated
      with improvement in gait speed. A benefit on trunk sway could not be
      demonstrated.

PMID- 25369891
TI  - Large (>3.8 cm) clear cell renal cell carcinomas are morphologically and
      immunohistochemically heterogeneous.
AB  - Heterogeneity is an inherent event to tumour development that is lately receiving
      much attention in oncologic research. The topic is being addressed primarily at
      the molecular level, and results are promising. However, translation to practical
      medicine is still pending. Our intention in this study is to approach the problem
      in a series of clear cell renal cell carcinomas with the tools that pathologists
      use in routine practice. Three randomly selected areas of 48 clear cell renal
      cell carcinomas prospectively collected in two different institutions were
      analysed for intratumour heterogeneity. The evaluated parameters were tumour
      size, cell type (clear vs. eosinophilic), Fuhrman's grade and immunohistochemical
      expression of carbonic anhydrase IX, BRCA1-associated protein-1 (BAP-1),
      cyclooxygenase-2 (COX-2) and Ki67. Intratumour heterogeneity was detected in 26
      cases (54 %). Cell type, grade and Ki67 index were the parameters more frequently
      heterogeneous amounting, respectively, 44, 42 and 38 %. Tumour size was a
      significantly discriminative factor to predict tumour heterogeneity, with a cut
      off of 3.8 cm (p < 0.001). Aside from tumour size, the most relevant parameters
      related with intratumour heterogeneity were cell type (clear vs. eosinophilic),
      Fuhrman's grade and Ki67 and COX-2 expression patterns. Carbonic anhydrase 9 and
      BAP-1 did not show statistical relevance. We conclude that heterogeneity is a
      common event in clear cell renal cell carcinomas that may be overlooked in cases
      insufficiently sampled. Tumour size appears as a reliable tool in identifying
      this situation since clear cell renal cell carcinomas under 3.8 cm in diameter
      are always homogeneous. This point may help the pathologist to make decisions in
      tumour sampling.

PMID- 25369892
TI  - Heterogeneity of DNA methylation in multifocal prostate cancer.
AB  - Most prostate cancer (PCa) cases are multifocal, and separate foci display
      histological and molecular heterogeneity. DNA hypermethylation is a frequent
      alteration in PCa, but interfocal heterogeneity of these changes has not been
      extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign
      prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens,
      resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to
      evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of
      selected TSGs was quantitatively analyzed for methylation intensity by
      pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated
      in all paired PCa foci, and frequent (>=75 %) DNA methylation was detected in
      RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at
      least one gene in separate foci in 8 out of 10 multifocal tumors. The mean
      methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired
      foci of all PCa cases. The intensity of DNA methylation in these TSGs was
      significantly higher in PCa cases than in BPH (p < 0.001). Hierarchical cluster
      analysis revealed a divergent methylation profile of paired PCa foci, while the
      foci from separate cases with biochemical recurrence showed similar methylation
      profile and the highest mean levels of DNA methylation. Our findings suggest that
      PCa tissue is heterogeneous, as between paired foci differences in DNA
      methylation status were found. Common epigenetic profile of recurrent tumors can
      be inferred from our data.

PMID- 25369893
TI  - Cloning, overexpression, and characterization of a highly active endoinulinase
      gene from Aspergillus fumigatus Cl1 for production of inulo-oligosaccharides.
AB  - In this study, an endoinulinase gene from Aspergillus fumigatus was cloned and
      overexpressed in Pichia pastoris. A maximum activity, 3860 U/ml, of the
      recombinant endoinulinase was obtained by using a high cell-density fermentation
      approach. The recombinant endoinulinase with a molecular weight of 58 kDa was
      purified for further enzymatic investigation. The pH and temperature optima were
      pH 6.0 and 55  degrees C, and the K m and V max values toward inulin were 2.18 mM
      and 1590 MUmol min(-1) mg(-1), respectively. The degree of polymerization (DP)
      for inulo-oligosaccharides product 3, 4, 5, and >5 was determined by thin-layer
      chromatography (TLC) and high-performance liquid chromatograph (HPLC).
      Immobilized endoinulinases were prepared and characterized, which showed higher
      stability than the free endoinulinase under various temperature levels. A
      residual activity of 81.2 % could be still obtained after ten reaction cycles.
      Thus, the present recombinant endoinulinase exhibited great potential for scale
      up production of inulo-oligosaccharides.

PMID- 25369894
TI  - Evaluation of the removal of pyrene and fluoranthene by Ochrobactrum anthropi,
      Fusarium sp. and their coculture.
AB  - Fluoranthene and pyrene are polycyclic aromatic hydrocarbons of high molecular
      weight that are recalcitrant and toxic to humans; therefore, their removal from
      the environment is crucial. From hydrocarbon-contaminated soil, 25 bacteria and
      12 filamentous fungi capable of growth on pyrene and fluoranthene as the sole
      carbon and energy source were isolated. From these isolates, Ochrobactrum
      anthropi BPyF3 and Fusarium sp. FPyF1 were selected and identified because they
      grew quickly and abundantly in both hydrocarbons. Furthermore, O. anthropi BPyF3
      and Fusarium sp. FPyF1 were most efficient at removing pyrene (50.39 and 51.32 %,
      respectively) and fluoranthene (49.85 and 49.36 %, respectively) from an initial
      concentration of 50 mg L(-1) after 7 days of incubation. Based on this and on the
      fact that there was no antagonism between the two microorganisms, a coculture
      composed of O. anthropi BPyF3 and Fusarium sp. FPyF1 was formed to remove
      fluoranthene and pyrene at an initial concentration of 100 mg L(-1) in a removal
      kinetic assay during 21 days. Fluoranthene removal by the coculture was higher
      (87.95 %) compared with removal from the individual cultures (68.95 % for
      Fusarium sp. FPyF1 and 64.59 % for O. anthropi BPyF3). In contrast, pyrene
      removal by the coculture (99.68 %) was similar to that obtained by the pure
      culture of Fusarium sp. FPyF1 (99.75 %). The kinetics of removal for both
      compounds was adjusted to a first-order model. This work demonstrates that the
      coculture formed by Fusarium sp. FPyF1 and O. anthropi BPyF3 has greater
      potential to remove fluoranthene than individual cultures; however, pyrene can be
      removed efficiently by Fusarium sp. FPyF1 alone.

PMID- 25369895
TI  - Hydrolysis of wheat arabinoxylan by two acetyl xylan esterases from Chaetomium
      thermophilum.
AB  - The thermophilic filamentous ascomycete Chaetomium thermophilum produces
      functionally diverse hemicellulases when grown on hemicellulose as carbon source.
      Acetyl xylan esterase (EC 3.1.1.72) is an important accessory enzyme in
      hemicellulose biodegradation. Although the genome of C. thermophilum has been
      sequenced, its carbohydrate esterases are not annotated yet. We applied peptide
      pattern recognition (PPR) tool for sequence analysis of the C. thermophilum
      genome, and 11 carbohydrate esterase genes were discovered. Furthermore, we
      cloned and heterologously expressed two putative acetyl xylan esterase genes,
      CtAxeA and CtAxeB, in Pichia pastoris. The recombinant proteins, rCtAxeA and
      rCtAxeB, released acetic acids from p-nitrophenyl acetate and water-insoluble
      wheat arabinoxylan. These results indicate that CtAxeA and CtAxeB are true acetyl
      xylan esterases. For both recombinant esterases, over 93 % of the initial
      activity was retained after 24 h of incubation at temperatures up to 60  degrees
      C, and over 90 % of the initial activity was retained after 24 h of incubation in
      different buffers from pH 4.0 to 9.0 at 4 and 50  degrees C. The overall xylose
      yield from wheat arabinoxylan hydrolysis was 8 % with xylanase treatment and
      increased to 34 % when xylanase was combined with rCtAxeA and rCtAxeB. In sum,
      the present study first report the biochemical characterization of two acetyl
      xylan esterases from C. thermophilum, which are efficient in hydrolyzing
      hemicellulose with potential application in biomass bioconversion to high value
      chemicals or biofuels.

PMID- 25369896
TI  - Microalgal cell disruption via ultrasonic nozzle spraying.
AB  - The objective of this study was to understand the effect of operating parameters,
      including ultrasound amplitude, spraying pressure, nozzle orifice diameter, and
      initial cell concentration on microalgal cell disruption and lipid extraction in
      an ultrasonic nozzle spraying system (UNSS). Two algal species including
      Scenedesmus dimorphus and Nannochloropsis oculata were evaluated. Experimental
      results demonstrated that the UNSS was effective in the disruption of microalgal
      cells indicated by significant changes in cell concentration and Nile red-stained
      lipid fluorescence density between all treatments and the control. It was found
      that increasing ultrasound amplitude generally enhanced cell disruption and lipid
      recovery although excessive input energy was not necessary for best results. The
      effect of spraying pressure and nozzle orifice diameter on cell disruption and
      lipid recovery was believed to be dependent on the competition between ultrasound
      induced cavitation and spraying-generated shear forces. Optimal cell disruption
      was not always achieved at the highest spraying pressure or biggest nozzle
      orifice diameter; instead, they appeared at moderate levels depending on the
      algal strain and specific settings. Increasing initial algal cell concentration
      significantly reduced cell disruption efficiency. In all UNSS treatments, the
      effectiveness of cell disruption and lipid recovery was found to be dependent on
      the algal species treated.

PMID- 25369897
TI  - Erratum to: The effect of nocturnal blue light exposure from light-emitting
      diodes on wakefulness and energy metabolism the following morning.

PMID- 25369899
TI  - Healthy cognitive ageing with a healthier diet and better nutrition?

PMID- 25369898
TI  - Complete and ubiquitinated proteome of the Legionella-containing vacuole within
      human macrophages.
AB  - Within protozoa or human macrophages Legionella pneumophila evades the endosomal
      pathway and replicates within an ER-derived vacuole termed the Legionella
      containing vacuole (LCV). The LCV membrane-localized AnkB effector of L.
      pneumophila is an F-box protein that mediates decoration of the LCV with
      lysine(48)-linked polyubiquitinated proteins, which is essential for
      intravacuolar replication. Using high-throughput LC-MS analysis, we have
      identified the total and ubiquitinated host-derived proteome of LCVs purified
      from human U937 macrophages. The LCVs harboring the AA100/130b WT strain contain
      1193 proteins including 24 ubiquitinated proteins, while the ankB mutant LCVs
      contain 1546 proteins with 29 ubiquitinated proteins. Pathway analyses reveal the
      enrichment of proteins involved in signaling, protein transport,
      phosphatidylinositol, and carbohydrate metabolism on both WT and ankB mutant
      LCVs. The ankB mutant LCVs are preferentially enriched for proteins involved in
      transcription/translation and immune responses. Ubiquitinated proteins on the WT
      strain LCVs are enriched for immune response, signaling, regulation,
      intracellular trafficking, and amino acid transport pathways, while ubiquitinated
      proteins on the ankB mutant LCVs are enriched for vesicle trafficking, signaling,
      and ubiquitination pathways. The complete and ubiquitinated LCV proteome within
      human macrophages illustrates complex and dynamic biogenesis of the LCV and
      provides a rich resource for future studies. 

PMID- 25369900
TI  - Role of vascular inflammation in coronary artery disease: potential of anti
      inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti
      inflammatory drugs in coronary artery disease.
AB  - Coronary artery disease (CAD) and acute myocardial infarction (AMI) are
      inflammatory pathologies, involving interleukins (ILs), such as IL-1beta, IL-6
      and tumor necrosis factor (TNF)-alpha, and acute phase proteins production, such
      as for C reactive protein (CRP). The process begins with retention of low-density
      lipoprotein (LDL) and its oxidation inside the intima, with the formation of the
      "foam cells." Toll-like receptors and inflamassomes participate in
      atherosclerosis formation, as well as in the activation of the complement system.
      In addition to innate immunity, adaptive immunity is also associated with
      atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also
      increases the expression of some ILs and promotes macrophage and lymphocyte
      accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such
      as IL-10) and generates oxygen free radicals. Although CAD and AMI are
      inflammatory disorders, the only drugs with anti-inflammatory effect so far
      widely used in ischemic heart disease are aspirin and statins. Some
      immunomodulatory or immunosuppressive promising therapies, such as cyclosporine
      and colchicine, may have benefits in CAD. Methotrexate also has potential
      cardioprotective anti-inflammatory effects, through increased adenosine levels.
      The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation
      MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation
      AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will
      evaluate low-dose methotrexate in patients with a high prevalence of subclinical
      vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis
      Outcomes Study) will evaluate canakinumab in patients with CAD and persistently
      elevated CRP. The blockage of other potential targets, such as the IL-6 receptor,
      CC2 chemokine receptor and CD20, could bring benefits in CAD. 

PMID- 25369901
TI  - Parasitoid flies exploiting acoustic communication of insects-comparative aspects
      of independent functional adaptations.
AB  - Two taxa of parasitoid Diptera have independently evolved tympanal hearing organs
      to locate sound producing host insects. Here we review and compare functional
      adaptations in both groups of parasitoids, Ormiini and Emblemasomatini. Tympanal
      organs in both groups originate from a common precursor organ and are somewhat
      similar in morphology and physiology. In terms of functional adaptations, the
      hearing thresholds are largely adapted to the frequency spectra of the calling
      song of the hosts. The large host ranges of some parasitoids indicate that their
      neuronal filter for the temporal patterns of the calling songs are broader than
      those found in intraspecific communication. For host localization the night
      active Ormia ochracea and the day active E. auditrix are able to locate a sound
      source precisely in space. For phonotaxis flight and walking phases are used,
      whereby O. ochracea approaches hosts during flight while E. auditrix employs
      intermediate landings and re-orientation, apparently separating azimuthal and
      vertical angles. The consequences of the parasitoid pressure are discussed for
      signal evolution and intraspecific communication of the host species. This
      natural selection pressure might have led to different avoidance strategies in
      the hosts: silent males in crickets, shorter signals in tettigoniids and
      fluctuating population abundances in cicadas.

PMID- 25369902
TI  - Nycthemeral variation in melatonin receptor expression in the lymphoid organs of
      a tropical seasonal breeder Funambulus pennanti.
AB  - Seasonal variations in immune functions point toward the involvement of melatonin
      in its regulation. These chronobiotic effects are exerted by receptors present on
      the immunocompetent cells. The present study investigated daily/nycthemeral
      variation in expression of melatonin receptor subtypes MT1/MT2 in the lymphoid
      organs (spleen/thymus) of a tropical squirrel, Funambulus pennanti. The receptor
      expression was noted every 4 h interval over 24 h under natural light-dark cycle,
      during two seasons and was correlated with peripheral level of melatonin. The
      MT1/MT2 receptor expression displayed higher levels at the time of dusk (light
      dark transition; 1800 hours), while plasma melatonin was still low compared to
      the preceding time point. The receptors were downregulated during the nighttime
      with a minimum expression at 0200 hours. Thymus, during the long day length,
      showed a tissue-specific pattern of receptor expression with a minimum expression
      at 0600 hours. Results suggest that photoperiod by modulation of melatonin level
      inversely regulates the receptor expression. The observations imply that there
      exists a temporal window of sensitivity in the target organs to the melatonin
      signal that is regulated by modulation of melatonin receptor expression which
      might be involved in mediating the photoperiodic effects of melatonin in the
      control of seasonal immune physiology.

PMID- 25369904
TI  - Fano resonance and dipolar relaxation in lead-free relaxors.
AB  - Fano resonance is a phenomenon in which a discrete state interferes with a
      continuum of states and has been observed in many areas of science. Here, we
      report on the prediction of a Fano resonance in ferroelectric relaxors, whose
      properties are poorly understood: an ab initio molecular dynamic scheme reveals
      such resonance between the bare optical phonon mode of the Zr sublattice (the
      discrete state) and the bare optical phonon mode of the Ti sublattice (the
      continuum of states) in disordered lead-free Ba(Zr,Ti)O3. The microscopic origins
      of the discrete state and continuum of states are discussed in the context of
      relaxor properties. Furthermore, our simulations suggest that the T*
      characteristic temperature of relaxor is related to a hardening of the
      vibrational frequencies associated with fluctuation of the Ti sublattice.
      Finally, a terahertz relaxation mode reflecting reorientations of Ti dipoles and
      showing a thermally activated behaviour is predicted, in agreement with previous
      experiments. 

PMID- 25369903
TI  - [Wasp-sting-induced pheochromozytoma crisis with stress-related cardiomyopathy
      (Takotsubo)].
AB  - This article presents the case of a patient with sudden onset of heart failure
      caused by transient severe left ventricular dysfunction with the typical pattern
      of stress-induced cardiomyopathy (takotsubo cardiomyopathy) who had wasp sting a
      few hours before admission in the presence of a previously asymptomatic
      pheochromocytoma. There seems to be correlation between the wasp-venom-induced
      pheochomocytoma crisis and acute onset of heart failure. Once pheocromocytoma is
      diagnosed, medical therapy is preferable before surgical treatment. This case
      demonstrates that a previously asymptomatic pheochromocytoma can become
      clinically relevant by catecholamine-releasing wasp venom causing stress-related
      cardiomyopathy and that patient history is mandatory for evaluating the cause of
      sudden clinical outcome.

PMID- 25369905
TI  - Personality and risk for postpartum depressive symptoms.
AB  - Postpartum depression (PPD) is a common childbirth complication, affecting 10-15
      % of newly delivered mothers. This study aims to assess the association between
      personality factors and PPD. All pregnant women during the period September 2009
      to September 2010, undergoing a routine ultrasound at Uppsala University
      Hospital, were invited to participate in the BASIC study, a prospective study
      designed to investigate maternal well-being. Depressive symptoms were assessed
      with the Edinburgh Postnatal Depression Scale (EPDS) while the Depression Self
      Rating Scale (DSRS) was used as a diagnostic tool for major depression.
      Personality traits were evaluated using the Swedish Universities Scale of
      Personality (SSP). One thousand thirty-seven non-depressed pregnant women were
      included in the study. Non-depressed women reporting high levels of neuroticism
      in late pregnancy were at high risk of developing postpartum depressive symptoms
      (PPDSs) at 6 weeks and 6 months after delivery, even after adjustment for
      confounders (adjusted odds ratio (aOR) = 3.4, 95 % confidence interval (CI) 1.8
      6.5 and adjusted odds ratio (aOR) = 3.9, 95 % CI 1.9-7.9). The same was true for
      a DSRS-based diagnosis of major depression at 6 months postpartum. Somatic trait
      anxiety and psychic trait anxiety were associated with increased risk for PPDS at
      6 weeks (aOR = 2.1, 95 % CI 1.2-3.5 and aOR = 1.9, 95 % CI 1.1-3.1), while high
      scores of mistrust were associated with a twofold increased risk for PPDS at 6
      months postpartum (aOR 1.9, 95 % CI 1.1-3.4). Non-depressed pregnant women with
      high neuroticism scores have an almost fourfold increased risk to develop
      depressive symptoms postpartum, and the association remains robust even after
      controlling for most known confounders. Clinically, this could be of importance
      for health care professionals working with pregnant and newly delivered women. 

PMID- 25369906
TI  - Depression improvement and parenting in low-income mothers in home visiting.
AB  - Research on older children and high-resource families demonstrates that maternal
      improvement in depression often leads to parallel changes in parenting and child
      adjustment. It is unclear if this association extends to younger children and low
      income mothers. This study examined if In-Home Cognitive Behavioral Therapy (IH
      CBT), a treatment for depressed mothers participating in home visiting programs,
      contributes to improvements in parenting and child adjustment. Ninety-three
      depressed mothers in home visiting between 2 and 10 months postpartum were
      randomly assigned to IH-CBT (n = 47) plus home visiting or standard home visiting
      (SHV; n = 46). Mothers were identified via screening and subsequent diagnosis of
      major depressive disorder (MDD). Measures of depression, parenting stress,
      nurturing parenting, and child adjustment were administered at pre-treatment,
      post-treatment, and 3 months follow-up. Results indicated that there were no
      differences between IH-CBT and controls on parenting and child adjustment. Low
      levels of depression were associated with decreased parenting stress and
      increased nurturing parenting. Improvement in depression was related to changes
      in parenting in low-income mothers participating in home visiting programs. IH
      CBT was not independently associated with these improvements, although to the
      extent that treatment facilitated improvement; there were corresponding benefits
      to parenting. Child adjustment was not associated with maternal depression, a
      finding possibly attributed to the benefits of concurrent home visiting or
      measurement limitations. Future research should focus on longer-term follow-up,
      implications of relapse, and child adjustment in later years. 

PMID- 25369908
TI  - Prognostic significance of vestibulospinal abnormalities in patients with
      vestibular migraine.
AB  - OBJECTIVES: We evaluated vestibular function test results in vestibular migraine
      (VM) patients, including caloric, vestibular evoked myogenic potential (VEMP),
      and dynamic posturography measurements and assessed their relationship with
      treatment responses. STUDY DESIGN: Retrospective case series review. SETTING:
      Tertiary referral center. METHODS: We investigated a cohort of 80 VM patients who
      had suffered recurrent vertigo attacks for more than 6 months. A combination of
      lifestyle modifications and prophylactic medications were used to treat these
      subjects. The patients were asked to score the treatment success by ranking
      symptom score from 0% to 100% for the improvement in overall severity of headache
      and vertigo. Patients were then classified as complete remission, symptomatic
      improvement 50% or more, or less than 50% improvement after 6 months of
      treatment. The periods needed for symptomatic improvement in the 50% or more
      patient group were recorded, and the responsiveness to medications and the
      vestibular test result metrics were analyzed to identify clinical outcome
      predictors. RESULTS: A symptomatic improvement of 50% or more in vertigo and
      headache was observed in 71% and 75% of the study subjects across mean periods of
      2.3 and 2.2 months, respectively. Improvements in vertigo and headache did not
      coincide in all. Abnormal caloric, VEMP, and vestibular ratio measurements were
      found in 25%, 29%, and 58%, respectively. Abnormal vestibular ratios on
      posturography showed a significant correlation with a poor treatment response of
      vertigo, and a normal VEMP was significantly related to complete remission from
      headache, although abnormal caloric results showed no significant correlation
      with treatment responses. A poor response of vertigo symptoms was observed in 6%
      of patients with a normal vestibular ratio and 48% of patients with abnormal
      vestibular ratio. Complete remission from headache was observed in 61% of
      patients with a normal VEMP and 30% in patients with an abnormal VEMP.
      CONCLUSION: More than 70% of the patients with VM experienced improvements in
      both headache and vertigo through a combination of lifestyle changes and
      prophylactic medications. Abnormal vestibular ratios on posturography and
      abnormal VEMP responses were frequent findings in VM patients with recurrent
      attacks for more than 6 months and were indicators of a poor prognosis. The
      pathophysiology of VM appears to be closely related to vestibular abnormalities,
      especially in vestibulospinal pathways. Further study with a large population is
      needed to establish the relationship exactly. LEVEL OF EVIDENCE: 2b Individual
      retrospective cohort study.

PMID- 25369907
TI  - Using the Patient Health Questionnaire (PHQ-9) and the Edinburgh Postnatal
      Depression Scale (EPDS) to assess suicidal ideation among pregnant women in Lima,
      Peru.
AB  - We sought to examine the concordance of two suicidal ideation items from the
      Patient Health Questionnaire-9 (PHQ-9) and the Edinburgh Postnatal Depression
      Scale (EPDS), to evaluate the prevalence of suicidal ideation among pregnant
      women, and to assess the co-occurrence of suicidal ideation with antepartum
      depressive symptoms. A cross-sectional study was conducted among 1,517 pregnant
      women attending prenatal care clinics in Lima, Peru. Item 9 of the PHQ-9 assesses
      suicidal ideation over the last 14 days while item 10 of the EPDS assesses
      suicidal ideation in the past 7 days. The two suicidal ideation items have a high
      concordance rate (84.2 %) but a moderate agreement (the Cohen's kappa = 0.42).
      Based on the PHQ-9 and the EPDS, 15.8 and 8.8 % of participants screened positive
      for suicidal ideation, respectively. Assessed by the PHQ-9, 51 % of participants
      with suicidal ideation had probable depression. In prenatal care clinics,
      screening for suicidal ideation is needed for women with and without depressive
      symptoms. Future studies are needed to identify additional predictors of
      antepartum suicidality, determine the appropriate duration of reporting period
      for suicidal ideation screening, and assess the percentage of individuals with
      positive responses to the two suicidal ideation items at high risk of planning
      and attempting suicide. 

PMID- 25369909
TI  - Inner Ear Inflammatory Pseudotumor With Middle Ear Cholesteatoma.

PMID- 25369910
TI  - Ubiquitin specific protease 22 promotes cell proliferation and tumor growth of
      epithelial ovarian cancer through synergy with transforming growth factor beta1.
AB  - Ubiquitin specific protease 22 (USP22) is an oncogene that is upregulated in many
      cancer types, and aberrant expression of USP22 correlates with clinical outcome.
      However, its potential functional impact in epithelial ovarian cancer (EOC) has
      not been determined. Here, we report that USP22 was upregulated in EOC specimens
      and EOC cell lines with important functional consequences. A high level of USP22
      in EOC tissues was associated with advanced clinical FIGO stage, lymph node
      metastasis and worse prognosis. Patients with higher USP22 expression had shorter
      relapse-free and overall survival. Depletion of USP22 suppressed cell
      proliferation in vitro and tumor growth in vivo. We found that inhibition of
      USP22 suppressed cell proliferation by inducing G1 phase cell cycle arrest
      through synergy with oncogenic transforming growth factor-beta1 (TGFB1). Our
      results indicate that USP22 functions as an oncogene in EOC, and thus USP22 may
      serve as a potential therapeutic target for individualized EOC treatment.

PMID- 25369911
TI  - Level anticrossing of impurity states in semiconductor nanocrystals.
AB  - The size dependence of the quantized energies of elementary excitations is an
      essential feature of quantum nanostructures, underlying most of their
      applications in science and technology. Here we report on a fundamental property
      of impurity states in semiconductor nanocrystals that appears to have been
      overlooked--the anticrossing of energy levels exhibiting different size
      dependencies. We show that this property is inherent to the energy spectra of
      charge carriers whose spatial motion is simultaneously affected by the Coulomb
      potential of the impurity ion and the confining potential of the nanocrystal. The
      coupling of impurity states, which leads to the anticrossing, can be induced by
      interactions with elementary excitations residing inside the nanocrystal or an
      external electromagnetic field. We formulate physical conditions that allow a
      straightforward interpretation of level anticrossings in the nanocrystal energy
      spectrum and an accurate estimation of the states' coupling strength.

PMID- 25369912
TI  - Variations in the natural 15N abundance of Brassica chinensis grown in
      uncultivated soil affected by different nitrogen fertilizers.
AB  - To further investigate the method of using delta(15)N as a marker for organic
      vegetable discrimination, the effects of different fertilizers on the delta(15)N
      in different growing stages of Brassica chinensis (B. chinensis) grown in
      uncultivated soil were investigated with a pot experiment. B. chinensis was
      planted with uncultivated soil and different fertilizer treatments and then
      harvested three times in three seasons consecutively. For the spring experiments
      in the years of 2011 and 2012, the delta(15)N value of B. chinensis, which
      increased due to organic manure application and decreased due to chemical
      fertilizer application, was significantly different (p < 0.05) with manure
      treatment and chemical treatment. The delta(15)N value of vegetables varied among
      three growing stages and ranged from +8.60/00 to +11.50/00 for the control, from
      +8.60/00 to +12.80/00 for the compost chicken manure treatment, from +2.80/00 to
      +7.70/00 for the chemical fertilizer urea treatment, and from +7.70/00 to
      +10.90/00 for the compost-chemical fertilizer treatment. However, the delta(15)N
      values observed in the autumn experiment of 2011 without any fertilizer
      application increased ranging from +13.40/00 to +15.40/00, + 11.20/00 to
      +17.70/00, +10.70/00 to +17.10/00, and +10.60/00 to +19.10/00, respectively, for
      the same treatments mentioned above. This result was not significantly different
      between manure treatment and chemical treatment. The delta(15)N values of soil
      obtained in the spring of 2011 during three growing stages were slightly affected
      by fertilizers and varied in the range of +1.60/00 to +2.50/00 for CK, +4.70/00
      to +6.50/00 for compost treatment, +2.10/00 to +2.40/00 for chemical treatment,
      and +2.70/00 to +4.60/00 for chemical-compost treatment, respectively. High
      delta(15)N values of B. chinensis were observed in these experiments, which would
      be useful to supplement a delta(15)N database for discriminating organic
      vegetables. Although there was a significant difference between manure treatment
      and chemical treatment, it was still difficult to discriminate whether a labeled
      organic vegetable was really grown without chemical fertilizer just with a fixed
      high delta(15)N value, especially for the vegetables planted simultaneously with
      chemical and compost fertilizer. 

PMID- 25369913
TI  - Toward development of an autonomous network of bacteria-based delivery systems
      (BacteriaBots): spatiotemporally high-throughput characterization of bacterial
      quorum-sensing response.
AB  - Characterization of bacterial innate and engineered cooperative behavior,
      regulated through chemical signaling in a process known as quorum sensing, is
      critical to development of a myriad of bacteria-enabled systems including
      biohybrid drug delivery systems and biohybrid mobile sensor networks. Here, we
      demonstrate, for the first time, that microfluidic diffusive mixers can be used
      for spatiotemporally high-throughput characterization of bacterial quorum-sensing
      response. Using this batch characterization method, the quorum-sensing response
      in Escherichia coli MG1655, transformed with a truncated lux operon from Vibrio
      fischeri, in the presence of 1-100 nM exogenous acyl-homoserine lactone molecules
      has been quantified. This method provides a rapid and facile tool for high
      throughput characterization of the quorum-sensing response of genetically
      modified bacteria in the presence of a wide concentration range of signaling
      molecules with a precision of +/-0.5 nM. Furthermore, the quorum-sensing response
      of BacteriaBots has been characterized to determine if the results obtained from
      a large bacterial population can serve as a robust predictive tool for the small
      bacterial population attached to each BacteriaBot. 

PMID- 25369914
TI  - MicroRNA-96 promotes the proliferation of colorectal cancer cells and targets
      tumor protein p53 inducible nuclear protein 1, forkhead box protein O1 (FOXO1)
      and FOXO3a.
AB  - MicroRNAs (miRNAs) are a conserved class of small, endogenous, non protein-coding
      RNA molecules that are capable of regulating gene expression at post
      transcriptional levels and are involved in diverse cellular processes, including
      cancer pathogenesis. It has previously been reported that miRNA-96 (miR-96) is
      overexpressed in human colorectal cancer (CRC). However, the underlying mechanism
      of miR-96 regulation in CRC remains to be elucidated. In the present study, miR
      96 was confirmed to be upregulated in CRC tissues by reverse transcription
      quantitative polymerase chain reaction. MTT assay, colony formation assay and
      cell cycle analysis revealed that miR-96 overexpression led to increased tumor
      cell viability, colony formation ability and cell cycle progression. By contrast,
      inhibition of miR-96 resulted in the suppression of cell proliferation. It was
      also demonstrated that miR-96 reduced the messenger RNA and protein expression
      levels of tumor protein p53 inducible nuclear protein 1 (TP53INP1), forkhead box
      protein O1 (FOXO1) and FOXO3a, which are closely associated with cell
      proliferation. A luciferase reporter assay indicated that miR-96 inhibited
      luciferase intensity controlled by the 3'UTRs of TP53INP1, FOXO1 and FOXO3a. In
      conclusion, the results of the present study demonstrated that miR-96 contributed
      to CRC cell growth and that TP53INP1, FOXO1 and FOXO3a were direct targets of miR
      96, suggesting that miR-96 may have the potential to be used in the development
      of miRNA-based therapies for CRC patients. 

PMID- 25369915
TI  - Wastewater treatment in a compact intensified wetland system at the Badboot: a
      floating swimming pool in Belgium.
AB  - The Badboot (Dutch for swimming pool boat) is a floating swimming pool located in
      the city center of Antwerp in Belgium. The overall design consists of a recycled
      ferry boat that serves as a restaurant and next to that a newly built ship that
      harbours an Olympic size swimming pool, sun decks, locker rooms with showers, and
      a party space. A major design goal of the project was to make the ship as
      environmentally friendly as possible. To avoid discharge of contaminated waste
      water in the Antwerp docks, the ship includes onsite treatment of wastewater in a
      compact constructed wetland. The treatment wetland system was designed to treat
      wastewater from visitor locker rooms, showers, toilets, two bars, and the
      wastewater from the restaurant kitchen. Due to the limited space on board the
      ship, only 188 m(2) could be allocated to a wetland treatment system. As a
      result, part of the design included intensification of the wetland treatment
      process through the use of Forced Bed Aeration, which injects small quantities of
      air in a very uniform grid pattern throughout the wetland with a mechanical air
      compressor. The system was monitored between August 2012 and March 2013 (with
      additional sampling in the autumn of 2014). Flows and loads to the wetland were
      highly variable, but removal efficiency was extremely high; 99.5 % for chemical
      oxygen demand (COD), 88.6 % for total nitrogen and 97.2 % for ammonia. The
      treatment performance was assessed using a first-order, tanks-in-series model
      (the P-k-C* model) and found to be roughly equivalent to similar intensified
      wetlands operating in Germany. However, treatment performance was substantially
      better than data reported on passive wetlands, likely as a result of
      intensification. Even with mechanically assisted aeration, the total oxygen
      delivered to the treatment wetlands was insufficient to support conventional
      nitrification and denitrification, so it is likely that alternate nitrogen
      removal pathways, such as anammox, are operating in the wetland. 

PMID- 25369916
TI  - Potential role of phytohormones and plant growth-promoting rhizobacteria in
      abiotic stresses: consequences for changing environment.
AB  - Plants are sessile beings, so the need of mechanisms to flee from unfavorable
      circumstances has provided the development of unique and sophisticated responses
      to environmental stresses. Depending on the degree of plasticity, many
      morphological, cellular, anatomical, and physiological changes occur in plants in
      response to abiotic stress. Phytohormones are small molecules that play critical
      roles in regulating plant growth and development, as well as stress tolerance to
      promote survival and acclimatize to varying environments. To congregate the
      challenges of salinity, temperature extremes, and osmotic stress, plants use
      their genetic mechanism and different adaptive and biological approaches for
      survival and high production. In the present attempt, we review the potential
      role of different phytohormones and plant growth-promoting rhizobacteria in
      abiotic stresses and summarize the research progress in plant responses to
      abiotic stresses at physiological and molecular levels. We emphasized the
      regulatory circuits of abscisic acid, indole acetic acid, cytokinins, gibberellic
      acid, salicylic acid, brassinosteroids, jasmonates, ethylene, and triazole on
      exposure to abiotic stresses. Current progress is exemplified by the
      identification and validation of several significant genes that enhanced crop
      tolerance to stress in the field. These findings will make the modification of
      hormone biosynthetic pathways for the transgenic plant generation with augmented
      abiotic stress tolerance and boosting crop productivity in the coming decades
      possible. 

PMID- 25369917
TI  - Denitrification kinetics in biomass- and biochar-amended soils of different
      landscape positions.
AB  - Knowledge of how biochar impacts soil denitrification kinetics as well as the
      mechanisms of interactions is essential in order to better predict the nitrous
      oxide (N2O) mitigation capacity of biochar additions. This study had multiple
      experiments in which the effect of three biochar materials produced from corn
      stover (Zea mays L.), ponderosa pine wood residue (Pinus ponderosa Douglas ex
      Lawson and C. Lawson), switchgrass (Panicum virgatum L.), and their corresponding
      biomass materials (corn stover, ponderosa pine wood residue, and switchgrass) on
      cumulative N2O emissions and total denitrification in soils from two different
      landscape positions (crest and footslope) were studied under varying water-filled
      pore space (40, 70, and 90% WFPS). Cumulative N2O emissions were reduced by 30 to
      70% in both crest and footslope soils. The effect of biochars and biomass
      treatments on cumulative N2O emissions and total denitrification were only
      observed at >=40% WFPS. The denitrification enzyme activity (DEA) kinetic
      parameters, K s (half-saturation constant), and V max (maximum DEA rate) were
      both significantly reduced by biochar treatments, with reductions of 70-80% in
      footslope soil and 80-90 % in the crest soil. The activation energy (E a) and
      enthalpy of activation of DEA (DeltaH) were both increased with biochar
      application. The trends in DEA rate constants (K s and V max) were correlated by
      the trends of thermodynamic parameters (activation energy E a and enthalpy of
      activation DeltaH) for denitrifying enzyme activity (DEA). The rate constant V
      max/K s evaluated the capacity of biochars to mitigate the denitrification
      process. Denitrifying enzyme kinetic parameters can be useful in evaluating the
      ability of biochars to mitigate N2O gas losses from soil.

PMID- 25369918
TI  - Microbial aerobic and anaerobic degradation of acrylamide in sludge and water
      under environmental conditions--case study in a sand and gravel quarry.
AB  - Polyacrylamides (PAMs) are used in sand and gravel quarries as water purification
      flocculants for recycling process water in a recycling loop system where the
      flocculants remove fine particles in the form of sludge. The PAM-based
      flocculants, however, contain residual amounts of acrylamide (AMD) that did not
      react during the polymerization process. This acrylamide is released into the
      environment when the sludge is discharged into a settling basin. Here, we explore
      the microbial diversity and the potential for AMD biodegradation in water and
      sludge samples collected in a quarry site submitted to low AMD concentrations.
      The microbial diversity, analyzed by culture-dependent methods and the denaturing
      gradient gel electrophoresis approach, reveals the presence of Proteobacteria,
      Cyanobacteria, and Actinobacteria, among which some species are known to have an
      AMD biodegradation activity. Results also show that the two main parts of the
      water recycling loop-the washing process and the settling basin-display
      significantly different bacterial profiles. The exposure time with residual AMD
      could, thus, be one of the parameters that lead to a selection of specific
      bacterial species. AMD degradation experiments with 0.5 g L(-1) AMD showed a high
      potential for biodegradation in all parts of the washing process, except the make
      up water. The AMD biodegradation potential in samples collected from the washing
      process and settling basin was also analyzed taking into account on-site
      conditions: low (12  degrees C) and high (25  degrees C) temperatures reflecting
      the winter and summer seasons, and AMD concentrations of 50 MUg L(-1). Batch
      tests showed rapid (as little as 18 h) AMD biodegradation under aerobic and
      anaerobic conditions at both the winter and summer temperatures, although there
      was a greater lag time before activity started with the AMD biodegradation at 12 
      degrees C. This study, thus, demonstrates that bacteria present in sludge and
      water samples exert an in situ and rapid biodegradation of AMD at low
      concentration, whatever the season, and in both the aerobic and anaerobic parts
      of the water recycling system.

PMID- 25369919
TI  - Beavers indicate metal pollution away from industrial centers in northeastern
      Poland.
AB  - Heavy metals are persistent environmental contaminants, and wild animals are
      increasingly exposed to the harmful effects of compounds of anthropogenic origin,
      even in areas distant from industrial centers. We used atomic absorption
      spectrometry to determine levels of cadmium (Cd), lead (Pb), copper (Cu), and
      zinc (Zn) in liver and kidney of wild Eurasian beavers (Castor fiber) in Poland.
      Cd concentrations in liver (0.21 +/- 0.44 MUg/g) and in kidney (2.81 +/- 4.52
      MUg/g) were lower in juvenile than in adult beavers. Pb concentrations in liver
      (0.08 +/- 0.03 MUg/g) and kidney (0.08 +/- 0.03 MUg/g) were similar among all
      individuals, while both Cu and Zn levels were higher in liver (Cu 9.2 +/- 4.5
      MUg/g; Zn 35.7 +/- 3.5 MUg/g) than in kidney (Cu 3.7 +/- 1.1 MUg/g; Zn 21.5 +/-
      2.7 MUg/g). Cu levels also differed between juveniles and adults. We reviewed the
      literature reporting metal concentrations in beavers. Our results indicate metal
      contamination in beavers away from important industrial emission sources and
      suggest the natural environment should be regularly monitored to ensure their
      levels are below recommended, legal values.

PMID- 25369921
TI  - Evaluation of variations and affecting factors of eco-environmental quality
      during urbanization.
AB  - Regional eco-environmental quality is the foundation of economic sustainable
      development and rational utilization of resources. It is necessary to understand
      and evaluate the regional eco-environmental quality correctly. Based on national
      remote sensing land use data, normalized difference vegetation index (NDVI) data
      and some other statistical data, this paper established an eco-environmental
      quality index (EQI) model to evaluate the ecological status of Jinan from 2000 to
      2011. The results of eco-environmental quality showed little variation, with EQI
      values ranged from 62.00 to 69.01. EQI of each region in Jinan firstly decreased
      sharply and then increased slowly with the development of local economy. Besides
      the spatial and temporal variations analysis, affecting factors of eco
      environmental quality was also discussed in this article. According to the
      results of correlation and regression analysis, meteorological conditions
      (rainfall and sunshine duration) and industrial structure (the proportion of
      primary industry) had relatively high correlations with eco-environmental
      quality. To summarize, a better eco-environmental status is associated with
      increasing rainfall, shorter sunshine duration, and lower proportion of primary
      industry. This article aims to giving supporting data and decision-making bases
      to restore the ecological environment and promote the sustainable development of
      Jinan. 

PMID- 25369920
TI  - Characterization of heavy metals and brominated flame retardants in the indoor
      and outdoor dust of e-waste workshops: implication for on-site human exposure.
AB  - Forty-four indoor and outdoor dust samples were collected from e-waste workshops
      and were analyzed to characterize the heavy metals and brominated flame
      retardants (BFRs) as well as on-site human exposure. The results showed that the
      most abundant Polybrominated diphenyl ethers (PBDE) congener from three sites was
      deca-BDE, and it was penta-BDE for the other site. A significant and positive
      association was found between BDE-209 and decabromodiphenyl ethane (DBDPE). The
      high percentage of nona-BDE indicated the debromination of deca-BDE during e
      waste recycling. The ratio comparison of BDE-47 to (BDE-100 + BDE-99) indicated
      that the outdoor dust went through more physiochemical processes. The enrichment
      factors for Cu and Pb were high in both the indoor and outdoor samples. Cd
      significantly exceeded the Chinese soil guideline grade III. The PCA results
      combined with the enrichment factor (EF) values suggested common sources and
      behaviours of Cu, Pb and Sb in the indoor dust. Co, Cr, Ni, Zn and Mn in the
      outdoor samples were more likely affected by crust. Strong correlations were
      found only for Pb and Sb with polybrominated diphenyl ethers (PBDEs). The hazard
      index for on-site human exposure to Pb was at a chronic risk. Despite the low
      deleterious risk of BFRs, concern should be given to DBDPE; the chronic toxicity
      of which is not known. 

PMID- 25369922
TI  - Versatile in vitro system to study translocation and functional integration of
      bacterial outer membrane proteins.
AB  - Gram-negative bacteria use the type-V secretion pathway to expose proteins at
      their cell surface, many of which have virulence functions. Translocation of
      those proteins across the outer membrane occurs either by means of dedicated
      translocator proteins (two-partner secretion) or covalently fused translocator
      domains (autotransporters). Translocator proteins and translocator domains are
      beta-barrels requiring the beta-barrel assembly machinery (BAM) for membrane
      integration. However, the molecular details of their passage across the envelope
      and insertion into the outer membrane remain enigmatic, owing in part to the fact
      that in vitro systems are not available. Here we describe a versatile in vitro
      reconstitution system that faithfully reproduces both branches of the type-V
      secretion pathway and the assembly of beta-barrel outer membrane proteins. This
      system will allow an in-depth analysis of protein secretion across and
      integration into outer membranes. 

PMID- 25369923
TI  - Iron and vegetarian diets.
AB  - Vegetarians who eat a varied and well balanced diet are not at any greater risk
      of iron deficiency anaemia than non-vegetarians. A diet rich in wholegrains,
      legumes, nuts, seeds, dried fruits, iron-fortified cereals and green leafy
      vegetables provides an adequate iron intake. Vitamin C and other organic acids
      enhance non-haem iron absorption, a process that is carefully regulated by the
      gut. People with low iron stores or higher physiological need for iron will tend
      to absorb more iron and excrete less. Research to date on iron absorption has not
      been designed to accurately measure absorption rates in typical Western
      vegetarians with low ferritin levels. 

PMID- 25369924
TI  - Zinc and vegetarian diets.
AB  - Well planned vegetarian diets can provide adequate amounts of zinc from plant
      sources. Vegetarians appear to adapt to lower zinc intakes by increased
      absorption and retention of zinc. Good sources of zinc for vegetarians include
      whole grains, tofu, tempeh, legumes, nuts and seeds, fortified breakfast cereals
      and dairy products. The inhibitory effects of phytate on absorption of zinc can
      be minimised by modern food-processing methods such as soaking, heating,
      sprouting, fermenting and leavening. Absorption of zinc can be improved by using
      yeast-based breads and sourdough breads, sprouts, and presoaked legumes. Studies
      show vegetarians have similar serum zinc concentrations to, and no greater risk
      of zinc deficiency than, non-vegetarians (despite differences in zinc intake). 

PMID- 25369925
TI  - Omega-3 polyunsaturated fatty acids and vegetarian diets.
AB  - While intakes of the omega-3 fatty acid alpha-linolenic acid (ALA) are similar in
      vegetarians and non-vegetarians, intakes of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) are low in vegetarians and virtually absent in vegans.
      Plasma, blood and tissue levels of EPA and DHA are lower in vegetarians than in
      non-vegetarians, although the clinical significance of this is unknown.
      Vegetarians do not exhibit clinical signs of DHA deficiency, but further research
      is required to ascertain whether levels observed in vegetarians are sufficient to
      support optimal health. ALA is endogenously converted to EPA and DHA, but the
      process is slow and inefficient and is affected by genetics, sex, age and dietary
      composition. Vegetarians can take practical steps to optimise conversion of ALA
      to EPA and DHA, including reducing intake of linoleic acid. There are no official
      separate recommendations for intake of fatty acids by vegetarians. However, we
      suggest that vegetarians double the current adequate intake of ALA if no direct
      sources of EPA and DHA are consumed. Vegetarians with increased needs or reduced
      conversion ability may receive some advantage from DHA and EPA supplements
      derived from microalgae. A supplement of 200-300 mg/day of DHA and EPA is
      suggested for those with increased needs, such as pregnant and lactating women,
      and those with reduced conversion ability, such as older people or those who have
      chronic disease (eg, diabetes).

PMID- 25369926
TI  - Vitamin B12 and vegetarian diets.
AB  - Vitamin B12 is found almost exclusively in animal-based foods and is therefore a
      nutrient of potential concern for those following a vegetarian or vegan diet.
      Vegans, and anyone who significantly limits intake of animal-based foods, require
      vitamin B12-fortified foods or supplements. Vitamin B12 deficiency has several
      stages and may be present even if a person does not have anaemia. Anyone
      following a vegan or vegetarian diet should have their vitamin B12 status
      regularly assessed to identify a potential problem. A useful process for
      assessing vitamin B12 status in clinical practice is the combination of taking a
      diet history, testing serum vitamin B12 level and testing homocysteine,
      holotranscobalamin II or methylmalonic acid serum levels. Pregnant and lactating
      vegan or vegetarian women should ensure an adequate intake of vitamin B12 to
      provide for their developing baby. In people who can absorb vitamin B12, small
      amounts (in line with the recommended dietary intake) and frequent (daily) doses
      appear to be more effective than infrequent large doses, including intramuscular
      injections. Fortification of a wider range of foods products with vitamin B12,
      particularly foods commonly consumed by vegetarians, is likely to be beneficial,
      and the feasibility of this should be explored by relevant food authorities.

PMID- 25369927
TI  - Meeting the nutrient reference values on a vegetarian diet.
AB  - Surveys over the past 10 years have shown that Australians are increasingly
      consuming more plant-based vegetarian meals. Many studies demonstrate the health
      benefits of vegetarian diets. As with any type of eating plan, vegetarian diets
      must be well planned to ensure nutritional needs are being met. This clinical
      focus project shows that well planned vegetarian diets can meet almost all the
      nutritional needs of children and adults of all ages. Sample single-day lacto-ovo
      vegetarian meal plans were developed to comply with the nutrient reference values
      - including the increased requirements for iron and zinc at 180% and 150%,
      respectively, for vegetarians - for both sexes and all age groups set by
      Australia's National Health and Medical Research Council and the New Zealand
      Ministry of Health. With the exception of vitamin D, long-chain omega-3 fatty
      acids and extended iron requirements in pregnancy for vegetarians, the meal plans
      meet key requirements with respect to energy; protein; carbohydrate; total fat;
      saturated, poly- and monounsaturated fats; alpha-linolenic acid; fibre; iron;
      zinc; calcium; folate; and vitamins A, C, E and B12.

PMID- 25369928
TI  - Practical tips for preparing healthy and delicious plant-based meals.

PMID- 25369929
TI  - A plant-based diet - good for us and for the planet.

PMID- 25369930
TI  - Protein and vegetarian diets.
AB  - A vegetarian diet can easily meet human dietary protein requirements as long as
      energy needs are met and a variety of foods are eaten. Vegetarians should obtain
      protein from a variety of plant sources, including legumes, soy products, grains,
      nuts and seeds. Eggs and dairy products also provide protein for those following
      a lacto-ovo-vegetarian diet. There is no need to consciously combine different
      plant proteins at each meal as long as a variety of foods are eaten from day to
      day, because the human body maintains a pool of amino acids which can be used to
      complement dietary protein. The consumption of plant proteins rather than animal
      proteins by vegetarians may contribute to their reduced risk of chronic diseases
      such as diabetes and heart disease. 

PMID- 25369931
TI  - Splitting, linking, knotting, and solitonic escape of topological defects in
      nematic drops with handles.
AB  - Topologically nontrivial field excitations, including solitonic, linked, and
      knotted structures, play important roles in physical systems ranging from
      classical fluids and liquid crystals, to electromagnetism, classic, and quantum
      field theories. These excitations can appear spontaneously during symmetry
      breaking phase transitions. For example, in cosmological theories, cosmic strings
      may have formed knotted configurations influencing the Early Universe
      development, whereas in liquid crystals transient tangled defect lines were
      observed during isotropic-nematic transitions, eventually relaxing to defect-free
      states. Knotted and solitonic fields and defects were also obtained using optical
      manipulation, complex-shaped colloids, and frustrated cholesterics. Here we use
      confinement of nematic liquid crystal by closed surfaces with varied genus and
      perpendicular boundary conditions for a robust control of appearance and
      stability of such field excitations. Theoretical modeling and experiments reveal
      structure of defect lines as a function of the surface topology and material and
      geometric parameters, establishing a robust means of controlling solitonic,
      knotted, linked, and other field excitations. 

PMID- 25369932
TI  - Cerebral small vessel disease-related protease HtrA1 processes latent TGF-beta
      binding protein 1 and facilitates TGF-beta signaling.
AB  - High temperature requirement protein A1 (HtrA1) is a primarily secreted serine
      protease involved in a variety of cellular processes including transforming
      growth factor beta (TGF-beta) signaling. Loss of its activity causes cerebral
      autosomal recessive arteriopathy with subcortical infarcts and
      leukoencephalopathy (CARASIL), an inherited form of cerebral small vessel disease
      leading to early-onset stroke and premature dementia. Dysregulated TGF-beta
      signaling is considered to promote CARASIL pathogenesis, but the underlying
      molecular mechanisms are incompletely understood. Here we present evidence from
      mouse brain tissue and embryonic fibroblasts as well as patient skin fibroblasts
      for a facilitating role of HtrA1 in TGF-beta pathway activation. We identify
      latent TGF-beta binding protein 1 (LTBP-1), an extracellular matrix protein and
      key regulator of TGF-beta bioavailability, as a novel HtrA1 target. Cleavage
      occurs at physiological protease concentrations, is prevented under HtrA1
      deficient conditions as well as by CARASIL mutations and disrupts both LTBP-1
      binding to fibronectin and its incorporation into the extracellular matrix.
      Hence, our data suggest an attenuation of TGF-beta signaling caused by a lack of
      HtrA1-mediated LTBP-1 processing as mechanism underlying CARASIL pathogenesis. 

PMID- 25369935
TI  - Trait-based extinction catches the Red Queen napping during the Cambrian.

PMID- 25369933
TI  - Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T
      cell leukemia.
AB  - Notch is needed for T-cell development and is a common oncogenic driver in T-cell
      acute lymphoblastic leukemia. The protooncogene c-Myc (Myc) is a critical target
      of Notch in normal and malignant pre-T cells, but how Notch regulates Myc is
      unknown. Here, we identify a distal enhancer located >1 Mb 3' of human and murine
      Myc that binds Notch transcription complexes and physically interacts with the
      Myc proximal promoter. The Notch1 binding element in this region activates
      reporter genes in a Notch-dependent, cell-context-specific fashion that requires
      a conserved Notch complex binding site. Acute changes in Notch activation produce
      rapid changes in H3K27 acetylation across the entire enhancer (a region spanning
      >600 kb) that correlate with Myc expression. This broad Notch-influenced region
      comprises an enhancer region containing multiple domains, recognizable as
      discrete H3K27 acetylation peaks. Leukemia cells selected for resistance to Notch
      inhibitors express Myc despite epigenetic silencing of enhancer domains near the
      Notch transcription complex binding sites. Notch-independent expression of Myc in
      resistant cells is highly sensitive to inhibitors of bromodomain containing 4
      (Brd4), a change in drug sensitivity that is accompanied by preferential
      association of the Myc promoter with more 3' enhancer domains that are strongly
      dependent on Brd4 for function. These findings indicate that altered long-range
      enhancer activity can mediate resistance to targeted therapies and provide a
      mechanistic rationale for combined targeting of Notch and Brd4 in leukemia. 

PMID- 25369934
TI  - Maresin 1 biosynthesis during platelet-neutrophil interactions is organ
      protective.
AB  - Unregulated acute inflammation can lead to collateral tissue injury in vital
      organs, such as the lung during the acute respiratory distress syndrome. In
      response to tissue injury, circulating platelet-neutrophil aggregates form to
      augment neutrophil tissue entry. These early cellular events in acute
      inflammation are pivotal to timely resolution by mechanisms that remain to be
      elucidated. Here, we identified a previously undescribed biosynthetic route
      during human platelet-neutrophil interactions for the proresolving mediator
      maresin 1 (MaR1; 7R,14S-dihydroxy-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid).
      Docosahexaenoic acid was converted by platelet 12-lipoxygenase to 13S,14S-epoxy
      maresin, which was further transformed by neutrophils to MaR1. In a murine model
      of acute respiratory distress syndrome, lipid mediator metabololipidomics
      uncovered MaR1 generation in vivo in a temporally regulated manner. Early MaR1
      production was dependent on platelet-neutrophil interactions, and intravascular
      MaR1 was organ-protective, leading to decreased lung neutrophils, edema, tissue
      hypoxia, and prophlogistic mediators. Together, these findings identify a
      transcellular route for intravascular maresin 1 biosynthesis via platelet
      neutrophil interactions that regulates the extent of lung inflammation. 

PMID- 25369936
TI  - Liat1, an arginyltransferase-binding protein whose evolution among primates
      involved changes in the numbers of its 10-residue repeats.
AB  - The arginyltransferase Ate1 is a component of the N-end rule pathway, which
      recognizes proteins containing N-terminal degradation signals called N-degrons,
      polyubiquitylates these proteins, and thereby causes their degradation by the
      proteasome. At least six isoforms of mouse Ate1 are produced through alternative
      splicing of Ate1 pre-mRNA. We identified a previously uncharacterized mouse
      protein, termed Liat1 (ligand of Ate1), that interacts with Ate1 but does not
      appear to be its arginylation substrate. Liat1 has a higher affinity for the
      isoforms Ate1(1A7A) and Ate1(1B7A). Liat1 stimulated the in vitro N-terminal
      arginylation of a model substrate by Ate1. All examined vertebrate and some
      invertebrate genomes encode proteins sequelogous (similar in sequence) to mouse
      Liat1. Sequelogs of Liat1 share a highly conserved ~30-residue region that is
      shown here to be required for the binding of Liat1 to Ate1. We also identified
      non-Ate1 proteins that interact with Liat1. In contrast to Liat1 genes of
      nonprimate mammals, Liat1 genes of primates are subtelomeric, a location that
      tends to confer evolutionary instability on a gene. Remarkably, Liat1 proteins of
      some primates, from macaques to humans, contain tandem repeats of a 10-residue
      sequence, whereas Liat1 proteins of other mammals contain a single copy of this
      motif. Quantities of these repeats are, in general, different in Liat1 of
      different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in
      the gibbon, gorilla, orangutan, bonobo, neanderthal, and human Liat1,
      respectively, suggesting that repeat number changes in this previously
      uncharacterized protein may contribute to evolution of primates. 

PMID- 25369939
TI  - Behavioral treatment of insomnia in early recovery.

PMID- 25369938
TI  - An evidence-based review of insomnia treatment in early recovery.
AB  - Accruing evidence indicates that insomnia is prevalent and persistent in early
      recovery from substance use disorders and may predict relapse. As such, insomnia
      treatment after abstinence represents an important area for intervention. This
      article reviews the literature on insomnia predicting new-onset alcohol and
      substance use disorders, along with evidence for insomnia predicting relapse in
      recovering populations. Pharmacological and psychological treatment options are
      presented, and cognitive-behavioral therapy for insomnia applied to recovering
      populations is described in detail. 

PMID- 25369937
TI  - Signaling pathways activated by a protease allergen in basophils.
AB  - Allergic diseases represent a significant burden in industrialized countries, but
      why and how the immune system responds to allergens remain largely unknown.
      Because many clinically significant allergens have proteolytic activity, and many
      helminths express proteases that are necessary for their life cycles, host
      mechanisms likely have evolved to detect the proteolytic activity of helminth
      proteases, which may be incidentally activated by protease allergens. A cysteine
      protease, papain, is a prototypic protease allergen that can directly activate
      basophils and mast cells, leading to the production of cytokines, including IL-4,
      characteristic of the type 2 immune response. The mechanism of papain's
      immunogenic activity remains unknown. Here we have characterized the cellular
      response activated by papain in basophils. We find that papain-induced IL-4
      production requires calcium flux and activation of PI3K and nuclear factor of
      activated T cells. Interestingly, papain-induced IL-4 production was dependent on
      the immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein Fc
      receptor gamma-chain, even though the canonical ITAM signaling was not activated
      by papain. Collectively, these data characterize the downstream signaling pathway
      activated by a protease allergen in basophils. 

PMID- 25369944
TI  - Less push, more pull.
AB  - Two of the biggest problems facing emergency department (ED) staff is that they
      have too many patients to manage and that hospitals do not move patients through
      the system fast enough. 

PMID- 25369943
TI  - Anion-tunable control of thermal Z->E isomerisation in basic azobenzene
      receptors.
AB  - Herein, we report that thermal Z->E isomerisation of simple azobenzene urea
      derivatives is selectively and predictably controlled by anion binding. The rate
      of this process depends strictly on the anion concentration and its binding
      affinity to the Z-isomer of the azobenzene host, i.e. increased rate constants
      are observed for higher anion concentration as well as for more strongly bound
      guests. The origin of this phenomenon is attributed to the electron density
      transfer from the anion to the host pi-system, resulting in increased repulsion
      between the lone electron pairs in the N=N bond.

PMID- 25369946
TI  - Equality legislation prompts revision of resuscitation guidance.
AB  - CLINICIANS WHOSE decisions on whether to carry out cardiopulmonary resuscitation
      are based on the patient's age or disability may be acting unlawfully, new
      guidance states. 

PMID- 25369941
TI  - Genetic variants in ADAM33 are associated with airway inflammation and lung
      function in COPD.
AB  - BACKGROUND: Genetic factors play a role in the development and severity of
      chronic obstructive pulmonary disease (COPD). The pathogenesis of COPD is a
      multifactorial process including an inflammatory cell profile. Recent studies
      revealed that single nucleotide polymorphisms (SNPs) within ADAM33 increased the
      susceptibility to COPD through changing the airway inflammatory process and lung
      function. METHODS: In this paper, we investigated associations of four
      polymorphisms (T1, T2, S2 and Q-1) of ADAM33 as well as their haplotypes with
      pulmonary function and airway inflammatory process in an East Asian population of
      patients with COPD. RESULTS: We found that T1, T2 and Q-1 were significantly
      associated with the changes of pulmonary function and components of cells in
      sputum of COPD, and T1 and Q-1 were significantly associated with cytokines and
      mediators of inflammation in airway of COPD in recessive models. 10 haplotypes
      were significantly associated with transfer factor of the lung for carbon
      monoxide in the disease state, 4 haplotypes were significantly associated with
      forced expiratory volume in one second, and other haplotypes were associated with
      airway inflammation. CONCLUSIONS: We confirmed for the first time that ADAM33 was
      involved in the pathogenesis of COPD by affecting airway inflammation and immune
      response in an East Asian population. Our results made the genetic background of
      COPD, a common and disabling disease, more apparent, which would supply genetic
      support for the study of the mechanism, classification and treatment for this
      disease.

PMID- 25369947
TI  - 'Ambitious' guideline for urgent care staff in development.
AB  - THE NATIONAL Institute for Health and Care Excellence (NICE) is to develop a
      guideline for NHS services that provide health and social care in emergencies. 

PMID- 25369948
TI  - Strategy announced to improve survival rate after cardiac arrest.
AB  - A STRATEGY to cut the number of deaths following out-of-hospital cardiac arrest
      is to be published next spring by the Scottish Government. 

PMID- 25369949
TI  - Toolkit may reduce number of admissions to hospital.
AB  - STAFF CAN identify emergency patients eligible for ambulatory care by using a
      toolkit published by the Royal College of Physicians (RCP). 

PMID- 25369951
TI  - Thirteen-fold increase in queries about legal highs.
AB  - POISON SPECIALISTS have flagged up rises in the number of calls and online
      queries about treatments for users of psychoactive substances known as 'legal
      highs'. 

PMID- 25369950
TI  - Retrieval and transfer service will be first of its kind in UK.
AB  - A NEW emergency service to stabilise and transfer the critically ill and injured
      patients to hospital by road and air will be operational in Wales from April. 

PMID- 25369952
TI  - Collaboration with community services can alleviate pressure.
AB  - PRESSURE ON urgent care services has been a constant theme in the NHS over the
      past decade. The number of emergency department (ED) admissions in England has
      grown over recent years, but NHS England medical director Sir Bruce Keogh thinks
      that it could soon decrease. 'You can reverse it if you provide alternatives for
      younger patients and get better at keeping older patients well,' he says. 

PMID- 25369953
TI  - Cardiopulmonary resuscitation update.
AB  - THE ROYAL College of Nursing (RCN), Resuscitation Council (UK) and British
      Medical Association (BMA) have issued a new edition of their guidance on when to
      attempt cardiopulmonary resuscitation (CPR). 

PMID- 25369954
TI  - Emergency nurses test NHS response to Ebola outbreak.
AB  - URGENT CARE staff should be aware that Ebola must be ruled out in all patients at
      their first point of contact in emergency departments (EDs), new guidance warns. 

PMID- 25369955
TI  - Board's eye view - Safe practices.
AB  - THE THEME for this year's annual conference of the Emergency Nurses Association,
      in Indianapolis, was 'safe practice, safe care'. 

PMID- 25369957
TI  - How Your Doctor Sees You: A Guide to the Body in X Rays and Scans Angus Robert
      How Your Doctor Sees You: A Guide to the Body in X Rays and Scans 191pp L12.99
      Farthings Publishing 9781291731132 129173113X [Formula: see text].
AB  - THE FORM, functions and inner workings of the human body are fascinating. This
      anatomy guide presents a range of medical images to illustrate how hospital
      doctors see the human body in their everyday practice. 

PMID- 25369956
TI  - Clinical EKG Modules Chiaramida Anthony and Green Jacqueline Clinical EKG Modules
      L37.25 Springer Publishing Company 9780826199768 0826199763 [Formula: see text].
AB  - THIS IS an easy-to-navigate educational DVD based on excellently reproduced
      electrocardiograms (ECGs) with accompanying case studies. 

PMID- 25369958
TI  - The bigger picture.
AB  - THE EMERGENCY Nurses Association's annual conference and international advisory
      council in Indianapolis last month gave RCN Emergency Care Association (ECA)
      committee members an opportunity to compare nursing issues in the UK with those
      in the US, Australia, Canada and mainland Europe. 

PMID- 25369959
TI  - Three-tier care.
AB  - IN RESPONSE to Nick Triggle's overview of Sir Bruce Keogh's service review in
      last month's Emergency Nurse, the concept of a two-tier emergency service has
      been generally accepted. 

PMID- 25369960
TI  - Answering the call.
AB  - EBOLA IS a highly dangerous infection and its management requires a great many
      resources. The recent outbreak of the virus has occurred in a rural area of west
      Africa with little medical infrastructure and technology, and few health
      facilities and professionals. 

PMID- 25369961
TI  - Diary.
AB  - Our roundup of what's on. 

PMID- 25369962
TI  - Noticeboard.
AB  - Courses, events, grants, and awards to progress your career. 

PMID- 25369964
TI  - Treating toxicity.
AB  - The use of lipid emulsions to resuscitate patients with toxicity due to local
      anaesthetics, such as bupivacaine cardiac toxicity, has been proposed in clinical
      literature. 

PMID- 25369963
TI  - Patient passport.
AB  - This article outlines the development, testing and evaluation of a patient
      passport designed specifically for people with severe asthma, who often prefer to
      self-manage rather than attend emergency services, and thereby put their lives at
      risk. 

PMID- 25369965
TI  - Cardiac arrest.
AB  - In this head-to-head debate, the authors provide opposing arguments about whether
      patients with cardiac arrest should be taken to hospital. 

PMID- 25369966
TI  - Pain management.
AB  - Pain management in emergency departments (EDs) is often inadequate because
      analgesia is delayed or insufficient. 

PMID- 25369967
TI  - Can ambulatory emergency care help to streamline services?
AB  - This article discusses four models of ambulatory emergency care (AEC), a form of
      clinical care that allows practitioners to assess, diagnose, treat and discharge
      patients on the same days that they present to emergency departments. The article
      recommends one model in particular, the process model, and sets out four
      questions practitioners who want to deliver AEC should ask of patients at the
      point of referral. 

PMID- 25369968
TI  - Preventing 'exit block' in emergency departments.
AB  - Overcrowding due to poor patient flow increases risk for more than 500,000
      patients a year ( College of Emergency Medicine (CEM) 2014 ) and is linked to
      increased mortality ( Geelhoed and de Klerk 2012 ). CEM ( 2014 ) has called for
      urgent action to address 'exit block' in UK emergency departments (EDs). In
      October last year, Croydon Health Services NHS Trust designed and implemented a
      site practitioner early warning system (SPEWS) to alert staff to capacity and
      flow pressures in the ED, and to initiate escalation to a nurse-led, protocol
      driven response. Under pressurised and time-critical conditions, SPEWS ensures
      rigour and conformity in exchanges between clinical emergency care staff and
      managers. The result is closer collaboration between clinicians and managers,
      optimised patient flow and mitigated risk from exit block. 

PMID- 25369969
TI  - How nurses can cope with stress and avoid burnout.
AB  - This article draws on a systematic literature review to identify stressors in
      emergency and trauma nursing settings, and their potential effects on staff.
      After a search of relevant databases, six articles were chosen and analysed, and
      the main causes of stress in the workplace for emergency and trauma nurses were
      identified. These stressors include work demands and lack of time, lack of
      managerial support, patient aggression and violence, and staff exposure to
      traumatic events. Their effects on nurses include burnout, compassion fatigue,
      somatic complaints, mental health problems and difficulties in life outside work.
      The article goes on to discuss the implications of the findings on practice. 

PMID- 25369971
TI  - Children's champion.
AB  - WHEN PAEDIATRIC emergency nurse consultant Jason Gray saw children waiting
      alongside adults for emergency care, and witnessing drunken or inappropriate
      behaviour while they waited, he decided to take action. 

PMID- 25369970
TI  - Importance of good teamwork in urgent care services.
AB  - High quality, safe care for patients depends on effective teamwork, and where
      multi-professional teams work together there is higher patient satisfaction,
      increased staff innovation, less stress and more communication ( West 2013 ).
      Conversely, lapses in teamwork and poor communication can result in adverse
      events ranging from retained foreign objects to perinatal events and medication
      errors ( Peter and Pronovost 2013 ), and even the death of patients (
      Resuscitation Council UK 2011 ). Teamwork requires a set of skills and behaviours
      that, once learned by clinicians, can save lives ( Peter and Pronovost 2013 ).
      This article refers to a case study to explore the topic of teamwork in a
      tertiary care emergency setting. 

PMID- 25369972
TI  - Chiral mononuclear lanthanide complexes and the field-induced single-ion magnet
      behaviour of a Dy analogue.
AB  - Three pairs of homochiral mononuclear lanthanide complexes, with the general
      formula [LnH4LRRRRRR/SSSSSS(SCN)2](SCN)2.xCH3OH.yH2O(Ln = Dy (R/S-Dy1), Ho (R/S
      Ho1) and Er (R/S-Er1)), have been obtained via self-assembly between chiral
      macrocyclic ligands and the respective thiocyanates, all of which show a saddle
      type conformation with seven-coordinated metal ions. Magnetic measurements
      revealed that the Dy complex shows field-induced single-ion magnet behaviour,
      which is rarely reported in a seven-coordinated lanthanide-based SIM encapsulated
      in a macrocyclic ligand. The absolute configuration of all enantiomers was
      determined by single crystal X-ray crystallography and confirmed by electronic CD
      and VCD spectra.

PMID- 25369973
TI  - A new phase transformation path from nanodiamond to new-diamond via an
      intermediate carbon onion.
AB  - The investigation of carbon allotropes such as graphite, diamond, fullerenes,
      nanotubes and carbon onions and mechanisms that underlie their mutual phase
      transformation is a long-standing problem of great fundamental importance. New
      diamond (n-diamond) is a novel metastable phase of carbon with a face-centered
      cubic structure; it is called "new diamond" because many reflections in its
      electron diffraction pattern are similar to those of diamond. However, producing
      n-diamond from raw carbon materials has so far been challenging due to n
      diamond's higher formation energy than that of diamond. Here, we, for the first
      time, demonstrate a new phase transformation path from nanodiamond to n-diamond
      via an intermediate carbon onion in the unique process of laser ablation in
      water, and establish that water plays a crucial role in the formation of n
      diamond. When a laser irradiates colloidal suspensions of nanodiamonds at ambient
      pressure and room temperature, nanodiamonds are first transformed into carbon
      onions serving as an intermediate phase, and sequentially carbon onions are
      transformed into n-diamonds driven by the laser-induced high temperature and high
      pressure from the carbon onion as a nanoscaled temperature and pressure cell upon
      the process of laser irradiation in a liquid. This phase transformation not only
      provides new insight into the physical mechanism involved, but also offers one
      suitable opportunity for breaking controllable pathways between n-diamond and
      carbon allotropes such as diamond and carbon onions. 

PMID- 25369974
TI  - Spigelian Hernias Treatment and Diagnosis in Our Experience.
AB  - AIM: Spigelian Hernia (SH) is a rare ventral hernia with a high incarceration and
      obstruction risk. The purpose of this study is to present our experience in
      diagnosis and treatment of this rare hernia entity. MATERIAL AND METHODS: The
      retrospective demographic characteristics, diagnostic tools and the surgical
      techniques of 17 patients who were treated between 2000-2010 are included in the
      study. RESULTS: All patients had swelling and pain. All patients underwent
      preperitoneal mesh repair. No mortality or morbidity were recorded
      postoperatively. No recurrence was detected at the end of a 73 (13-115) month
      follow-up period. CONCLUSIONS: Spigelian Hernia is a rare entity with a wide
      clinical spectrum and difficulties in preoperative diagnosis. Surgical mesh
      repair seems to decrease the complication and recurrence rates. KEY WORD: Hernia
      repair, Spigelian hernia, Surgery.

PMID- 25369975
TI  - Social capital, mortality, cardiovascular events  and cancer: a systematic review
      of  prospective studies.
AB  - BACKGROUND: Social capital is considered to be an important determinant of life
      expectancy and cardiovascular health. Evidence on the association between social
      capital and all-cause mortality, cardiovascular disease (CVD) and cancer was
      systematically reviewed. METHODS: Prospective studies examining the association
      of social capital with these outcomes were systematically sought in Medline,
      Embase and PsycInfo, all from inception to 8 October 2012. We categorized the
      findings from studies according to seven dimensions of social capital, including
      social participation, social network, civic participation,social support, trust,
      norm of reciprocity and sense of community, and pooled the estimates across
      studies to obtain summary relative risks of the health outcomes for each social
      capital dimension. We excluded studies focusing on children, refugees or
      immigrants and studies conducted in the former Soviet Union. RESULTS: Fourteen
      prospective studies were identified. The pooled estimates showed no association
      between most social capital dimensions and all-cause mortality, CVD or cancer.
      Limited evidence was found for association of increased mortality with social
      participation and civic participation when comparing the most extreme risk
      comparisons. CONCLUSIONS: Evidence to support an association between social
      capital and health outcomes is limited. Lack of consensus on measurements for
      social capital hinders the comparability of studies and weakens the evidence
      base.

PMID- 25369976
TI  - Evaluation of operational, economic, and environmental performance of mixed and
      selective collection of municipal solid waste: Porto case study.
AB  - This article describes an accurate methodology for an operational, economic, and
      environmental assessment of municipal solid waste collection. The proposed
      methodological tool uses key performance indicators to evaluate independent
      operational and economic efficiency and performance of municipal solid waste
      collection practices. These key performance indicators are then used in life
      cycle inventories and life cycle impact assessment. Finally, the life cycle
      assessment environmental profiles provide the environmental assessment. We also
      report a successful application of this tool through a case study in the
      Portuguese city of Porto. Preliminary results demonstrate the applicability of
      the methodological tool to real cases. Some of the findings focus a significant
      difference between average mixed and selective collection effective distance
      (2.14 km t(-1); 16.12 km t(-1)), fuel consumption (3.96 L t(-1); 15.37 L t(-1)),
      crew productivity (0.98 t h(-1) worker(-1); 0.23 t h(-1) worker(-1)), cost (45.90
      ? t(-1); 241.20 ? t(-1)), and global warming impact (19.95 kg CO2eq t(-1); 57.47
      kg CO2eq t(-1)). Preliminary results consistently indicate: (a) higher global
      performance of mixed collection as compared with selective collection; (b)
      dependency of collection performance, even in urban areas, on the waste
      generation rate and density; (c) the decline of selective collection performances
      with decreasing source-separated material density and recycling collection rate;
      and (d) that the main threats to collection route efficiency are the extensive
      collection distances, high fuel consumption vehicles, and reduced crew
      productivity.

PMID- 25369977
TI  - Treatment of colorectal liver metastases in Germany: a ten-year population-based
      analysis of 5772 cases of primary colorectal adenocarcinoma.
AB  - BACKGROUND: Purpose of this study was to analyse the surgical management and long
      term clinical outcome of patients diagnosed with colorectal liver metastases
      (CLM) over a period of 10 years using data from a German tumour registry.
      METHODS: Retrospective analysis of 5772 patients diagnosed with colorectal
      adenocarcinoma between 2002 and 2007. Follow-up was continued until 2012.
      RESULTS: 1426 patients (24.7%) had CLM; 1019 patients (71%) had synchronous, 407
      patients (29%) developed metachronous CLM. Hepatic resection was performed in 374
      of the 1426 CLM patients (26%). A significant increase in liver resection rate
      from 16.6% for the 2002 cohort to 32% in later cohorts was observed. In centers
      specialized in liver surgery, CLM resection rates reached 46.6%. However, up to
      52% of patients diagnosed with three or less CLM did not undergo liver surgery,
      although, if resected, patients with 1 CLM show a similar long-time survival as
      CRC patients who do not develop any CLM. Univariate and multivariate analyses
      adjusted for age, sex, year of resection, time of CLM diagnosis and number of CLM
      revealed a significant survival benefit for CLM resection (HR =0.355; CI 0.305
      0.414). Furthermore, significant impact on OS was seen for age at diagnosis,
      perioperative chemotherapy and number of CLM. CONCLUSIONS: We here present the
      first long-term, population-based analysis of the surgical management of CLM in
      Germany. Significant increase in hepatic resection rates, translating to a
      significant benefit in OS, was seen over years. However, we still see a striking
      potential for further improvements in interdisciplinary CLM management.

PMID- 25369978
TI  - Fecal calprotectin is an effective diagnostic tool that differentiates
      inflammatory from functional intestinal disorders.
AB  - BACKGROUND: The clinical pictures of functional gastrointestinal disorders and
      inflammatory diseases can be quite similar leading to inappropriate and expensive
      investigations. Objective. To investigate fecal calprotectin (FC) diagnostic
      performance in different gastrointestinal conditions. MATERIAL AND METHODS: Stool
      specimens of 66 outpatients referred for colonoscopy were collected for further
      FC determination. Diagnostic accuracy was assessed by the area under the curve
      (AUC). Sensitivity (Se), specificity (Sp), positive (PPV), and negative
      predictive values (NPV) were calculated according to the presence of inflammation
      and the main final diagnosis. RESULTS: Histological inflammation was found in 45
      (68%) patients: 24 had a diagnosis of inflammatory bowel disease (IBD) while 21
      reported miscellaneous conditions (5 microscopic colitis, 2 eosinophilic colitis,
      and 14 nonspecific chronic colitis). The diagnosis in the 21 (32%) patients
      without inflammation was irritable bowel syndrome (IBS). Median FC values were
      268 ug/g (95% CI, 151-343) and 49 ug/g (95% CI, 23-101) in patients with and
      without inflammation, respectively (p = 0.0001). AUC value of FC was 0.811 (Se =
      68.9%, Sp = 71.4%, PPV = 83.8%, and NPV = 56.3% with a cutoff value of 100 ug/g)
      for discriminating between patients with and without inflammation and 0.931 (Se =
      87.5%, Sp = 90.5%, PPV = 91.3%, and NPV = 86.4% with a cutoff value of 150 ug/g)
      for discriminating between patients with IBS and IBD. Using the cutoff value
      recommended by the manufacturer (50 ug/g), we found Se =100%, Sp =52.4%, PPV
      =70.6%, and NPV =100% for the diagnosis of IBD. CONCLUSIONS: FC appears to be a
      reliable noninvasive biomarker of intestinal inflammation useful to improve the
      appropriateness of colonoscopy requests.

PMID- 25369979
TI  - Interaction between the human cytomegalovirus-encoded UL142 and cellular Snapin
      proteins.
AB  - Human cytomegalovirus (HCMV) infection can cause severe illness in
      immunocompromised and immunodeficient individuals. As a novel HCMV-encoded major
      histocompatibility complex class I-related molecule, the UL142-encoded protein
      (pUL142) is capable of suppressing natural killer (NK) cell recognition in the
      course of infection. However, no host factors that directly interact with HCMV
      pUL142 have been reported so far. In order to understand the interactions between
      HCMV pUL142 and host proteins, the current study used yeast two-hybrid screening,
      a GST pull-down assay and an immunofluorescence assay. A host protein, the SNARE
      associated protein Snapin, was identified to directly interact and colocalize
      with HCMV pUL142 in transfected human embryonic kidney-293 cells. Snapin is
      abundantly expressed in the majority of cells and mediates the release of
      neurotransmitters through vesicular transport in the nervous system and vesicle
      fusion in non-neuronal cells. It is hypothesized that HCMV pUL142 may have an
      impact on the neurotransmitter release process and viral dissemination via
      interaction with Snapin. 

PMID- 25369980
TI  - Variation in absorption and half-life of hydrocortisone influence plasma cortisol
      concentrations.
AB  - BACKGROUND: Hydrocortisone therapy should be individualized in congenital adrenal
      hyperplasia (CAH) patients to avoid over and under replacement. We have assessed
      how differences in absorption and half-life of cortisol influence glucocorticoid
      exposure. PATIENTS AND METHODS: Forty-eight patients (21 M) aged between 6.1 and
      20.3 years with CAH due to CYP21A2 deficiency were studied. Each patient
      underwent a 24-h plasma cortisol profile with the morning dose used to calculate
      absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m(2)
      body surface area) bolus assessment of half-life. Parameters derived were maximum
      plasma concentration (Cmax ), time of maximum plasma concentration (tmax ), time
      to attaining plasma cortisol concentration <100 nmol/l and half-life of cortisol.
      RESULTS: Mean half-life was 76.5 +/- 5.2 (range 40-225.3) min, Cmax 780.7 +/-
      61.6 nmol/l and tmax 66.7 (range 20-118) min. Time taken to a plasma cortisol
      concentration less than 100 nmol/l was 289 (range 140-540) min. Those with a fast
      half-life and slow tmax took longest to reach a plasma cortisol concentration
      less than 100 nmol/l (380 +/- 34.6 min), compared to those with a slow half-life
      and fast tmax (298 +/- 34.8 min) and those with a fast half-life and fast tmax
      (249.5 +/- 14.4 min) (One-way anovaF = 4.52; P = 0.009). CONCLUSIONS: Both rate
      of absorption and half-life of cortisol in the circulation play important roles
      in determining overall exposure to oral glucocorticoid. Dose regimens need to
      incorporate estimates of these parameters into determining the optimum dosing
      schedule for individuals.

PMID- 25369981
TI  - Synthesis and in vitro anticancer activity of zinc(II) phthalocyanines conjugated
      with coumarin derivatives for dual photodynamic and chemotherapy.
AB  - The combination of photodynamic therapy and chemotherapy is a promising strategy
      to overcome growing problems in contemporary medicine, such as low therapeutic
      efficacy and drug resistance. Four zinc(II) phthalocyanine-coumarin conjugates
      were synthesized and characterized. In these complexes, zinc(II) phthalocyanine
      was used as the photosensitizing unit, and a coumarin derivative was selected as
      the cytostatic moiety; the two components were linked via a tri(ethylene glycol)
      chain. These conjugates exhibit high photocytotoxicity against HepG2 human
      hepatocarcinoma cells, with low IC50 values in the range of 0.014-0.044 MUM. The
      high photodynamic activities of these conjugates are in accordance with their low
      aggregation tendency and high cellular uptake. One of these conjugates exhibits
      high photocytotoxicity and significantly higher chemocytotoxicity. The results
      clearly show that the two antitumor components in these conjugates work in a
      cooperative fashion. As shown by confocal microscopy, the conjugates can localize
      in the mitochondria and lysosomes, and one of the conjugates can also localize in
      the cell nuclei.

PMID- 25369982
TI  - Biomimetic synthesis of the calcineurin phosphatase inhibitor dibefurin.
AB  - Dibefurin is a Ci -symmetric natural product that acts as an inhibitor of
      calcineurin phosphatase. A six-step synthesis of this compound is reported, which
      features an oxidative dimerization of the aromatic polyketide epicoccine as the
      key step. Dibefurin is proposed to be related to epicolactone, a complex yet
      racemic fungal metabolite that has recently been discovered. Attempts to access
      epicolactone from epicoccine and epicoccone B resulted in an unusual dimer that
      is formed through a hetero-Diels-Alder reaction of a para-quinone methide with an
      ortho-quinone. 

PMID- 25369983
TI  - Association between maternal single nucleotide polymorphisms in genes regulating
      glucose metabolism and risk for neural tube defects in offspring.
AB  - BACKGROUND: Maternal pregestational hyperglycemia, diabetes, and obesity are well
      established risk factors for neural tube defects (NTDs). As a common underlying
      mechanism, the imbalance of glucose homeostasis is directly related to the
      development of NTDs. Polymorphisms in genes regulating glucose metabolism in
      women may impact their chance of having an NTD-affected pregnancy. METHODS: We
      conducted a two-stage case-control study to investigate the association between
      maternal genetic variants in genes regulating glucose metabolism and risk for
      NTDs. The cases were 547 women who gave birth to a child with an NTD
      (anencephaly, spina bifida, or encephalocele); the controls were 543 women who
      gave birth to a full-term healthy infant. In the first stage, 12 single
      nucleotide polymorphisms were genotyped in 160 cases and 162 controls. In the
      second stage, five single nucleotide polymorphisms found in the first stage and
      potentially associated with NTD risk were genotyped for validation, in an
      additional 387 cases and 381 controls. RESULTS: Combined analysis of data from
      the two stages showed an association between maternal AA genotype of GCKR
      rs780094 and increased risk for total NTDs [odds ratio, 1.73; 95% confidence
      interval, 1.16-2.59) and spina bifida subtype [odds ratio, 1.83; 95% confidence
      interval, 1.16-2.88). No association was found between the other four single
      nucleotide polymorphisms (LEPR rs1137100, HK1 rs748235, HHEX rs5015480, KCNQ1
      rs2237892) and NTD risk. CONCLUSION: The AA genotype in maternal GCKR rs780094 is
      associated with an increased risk for NTDs and spina bifida in the Chinese
      population.

PMID- 25369984
TI  - Potential drug-drug interactions in cardiothoracic intensive care unit of a
      pulmonary teaching hospital.
AB  - Little is known about clinically significant drug-drug interactions (DDIs) in
      respiratory settings. DDIs are more likely to occur in critically ill patients
      due to complex pharmacotherapy regimens and organ dysfunctions. The aim of this
      study was to identify the pattern of potential DDIs (pDDIs) occurring in
      cardiothoracic intensive care unit (ICU) of a pulmonary hospital. A prospective
      observational study was conducted for 6 months. All pDDIs for admitted patients
      in cardiothoracic ICU were identified with Lexi-Interact program and assessed by
      a clinical pharmacologist. The interacting drugs, reliability, mechanisms,
      potential outcomes, and clinical management were evaluated for severe and
      contraindicated interactions. The study included 195 patients. Lung cancer
      (14.9%) was the most common diagnosis followed by tracheal stenosis (14.3%). The
      rate of pDDIs was 720.5/100 patients. Interactions were more commonly observed in
      transplant patients. 17.7% of pDDIs were considered as severe and contraindicated
      interactions. Metabolism (54.8%) and additive (24.2%) interactions were the most
      frequent mechanisms leading to pDDIs, and azole antifungals and fluoroquinolones
      were the main drug classes involved. The pattern of pDDIs in cardiothoracic ICU
      differs from other ICU settings. Specialized epidemiological knowledge of drug
      interactions may help clinical practitioners to reduce the risk of adverse drug
      events. 

PMID- 25369986
TI  - Evaluation of a joint distractor to facilitate arthroscopy of the hip joint in
      dogs.
AB  - OBJECTIVE: To evaluate the technical feasibility and efficacy of a hip joint
      distraction technique, any potential ligamentous damage linked to the procedure,
      and the effect of joint venting on the maximum distraction achieved. METHODS:
      Twenty hip joints from 11 canine cadavers were evaluated radiographically by
      standard and stressed projections. Joint distraction was applied with loads from
      40 up to 200 N, in 40 N increments, and fluoroscopic images were obtained at each
      load. At 200 N, a needle was inserted into the joint to achieve a venting effect,
      and the space was measured again. Standard and stressed radiographs were
      performed to evaluate potential laxity changes. RESULTS: Distraction caused a
      significant increase in joint space at each load of distraction, although there
      were some variations. Joint venting produced a significant increase in joint
      space. A statistically significant difference in joint laxity evaluated
      radiographically before and after the procedure was recorded. CLINICAL
      SIGNIFICANCE: Use of the distraction apparatus resulted in an increase in joint
      space. This could be useful for clinical situations where a larger joint space is
      required such as for arthroscopic procedures. However, loads in excess of 200 N
      may induce significant increases in joint laxity.

PMID- 25369985
TI  - Epidemiology of systemic lupus erythematosus and cutaneous lupus erythematosus in
      a predominantly white population in the United States.
AB  - OBJECTIVE: Epidemiologic studies comparing the incidence and prevalence of
      systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus
      (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a
      study owing to resources of the Rochester Epidemiology Project. We sought to
      describe and compare the incidence and prevalence of SLE and CLE from 1993-2005.
      METHODS: SLE cases were identified from review of medical records and fulfilled
      the 1982 American College of Rheumatology classification criteria. CLE cases
      included patients with classic discoid lupus erythematosus, subacute CLE, lupus
      panniculitis, and bullous lupus erythematosus. Age- and sex-adjusted incidence
      and prevalence were standardized to the 2000 US white population. RESULTS: The
      age- and sex-adjusted incidence of SLE (2.9 per 100,000; 95% confidence interval
      [95% CI] 2.0-3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1-5.2, P
      = 0.10). However, the incidence of CLE was 3 times higher than SLE in men (2.4
      versus 0.8 per 100,000; P = 0.009). The age- and sex-adjusted prevalence of CLE
      on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; P <
      0.001). The prevalences of CLE and SLE in women were similar, but the prevalence
      of CLE was higher in men than in women (56.9 versus 1.6 per 100,000; P < 0.001).
      The incidence of CLE rose steadily with age and peaked at 60-69 years.
      CONCLUSION: The incidences of CLE and SLE are similar, but CLE is more common
      than SLE in men and in older adults. These findings may reflect differences in
      genetic or environmental etiology of CLE.

PMID- 25369987
TI  - Abnormal cervicovaginal cytology, unsatisfactory colposcopy and the use of
      vaginal estrogen cream: an observational study of clinical outcomes for women in
      low estrogen states.
AB  - AIM: To determine the effectiveness of vaginal estrogen cream to improve the rate
      of satisfactory colposcopy and subsequent smear result in patients in a
      hypoestrogenic state and an abnormal Papanicolaou smear. To delineate between
      abnormal smears secondary to atrophy and inflammation from preneoplastic change
      and suggest an effective treatment strategy to deal with this challenging
      situation. METHODS: Patients with abnormal cervicovaginal smears who were in a
      low estrogen state (postmenopausal or amenorrheic postnatal) undergoing
      colposcopy were identified. All patients had an unsatisfactory colposcopy and
      were treated with vaginal estrogen cream twice per week for 6 weeks and underwent
      repeat colposcopy, smear and targeted biopsy where required. RESULTS: Fifty-four
      patients had an abnormal smear and were clinically in a low estrogen state, with
      four having previously had a hysterectomy. After 6 weeks of vaginal estrogen
      therapy, 32 out of 50 patients' colposcopic examinations were satisfactory. Also,
      40 out of 54 patients' smears returned to normal after treatment. Of the 14
      patients with persistent smear abnormalities, only three were diagnosed with true
      high-grade pre-invasive disease. CONCLUSION: The use of vaginal estrogen cream
      for patients with smear abnormalities and a low estrogen status improves the
      satisfactory colposcopy rate and improves the accuracy of the prediction of true
      high-grade pre-invasive disease. This treatment may then reduce the number of
      patients that require definitive treatment for their screen-detected
      abnormalities in this patient population.

PMID- 25369988
TI  - Complementarity of statistical treatments to reconstruct worldwide routes of
      invasion: the case of the Asian ladybird Harmonia axyridis.
AB  - Inferences about introduction histories of invasive species remain challenging
      because of the stochastic demographic processes involved. Approximate Bayesian
      computation (ABC) can help to overcome these problems, but such method requires a
      prior understanding of population structure over the study area, necessitating
      the use of alternative methods and an intense sampling design. In this study, we
      made inferences about the worldwide invasion history of the ladybird Harmonia
      axyridis by various population genetics statistical methods, using a large set of
      sampling sites distributed over most of the species' native and invaded areas. We
      evaluated the complementarity of the statistical methods and the consequences of
      using different sets of site samples for ABC inferences. We found that the H.
      axyridis invasion has involved two bridgehead invasive populations in North
      America, which have served as the source populations for at least six independent
      introductions into other continents. We also identified several situations of
      genetic admixture between differentiated sources. Our results highlight the
      importance of coupling ABC methods with more traditional statistical approaches.
      We found that the choice of site samples could affect the conclusions of ABC
      analyses comparing possible scenarios. Approaches involving independent ABC
      analyses on several sample sets constitute a sensible solution, complementary to
      standard quality controls based on the analysis of pseudo-observed data sets, to
      minimize erroneous conclusions. This study provides biologists without expertise
      in this area with detailed methodological and conceptual guidelines for making
      inferences about invasion routes when dealing with a large number of sampling
      sites and complex population genetic structures.

PMID- 25369990
TI  - Diabetes mellitus onset in geriatric patients: does long-term atypical
      antipsychotic exposure increase risk?
AB  - BACKGROUND: Diabetes mellitus (DM) in common in adults using psychotropic
      medications. However, it remains largely unknown whether there is an additional
      risk of diabetes mellitus (DM) in elderly psychiatric outpatients, particularly
      those with long-term exposure to atypical antipsychotics (AP). METHODS: In this
      retrospective longitudinal study, 61 atypical AP-exposed and 64 atypical AP
      unexposed geriatric psychiatric patients were compared to a group of 200
      psychotropic-naive controls. Our main composite outcome was diabetes incidence
      over a 4-year period, defined by fasting blood glucose >= 7.0 mmol/L or a new
      onset oral hypoglycaemic or insulin prescription during the 4-year period.
      RESULTS: The 4-year incidence of DM did not differ significantly between groups:
      12.3%, 6.7%, and 11.9% in the atypical AP-exposed, atypical AP-unexposed, and
      control groups, respectively (chi(2) = 1.40, P = 0.50). Depression and
      antidepressant, cholinesterase inhibitor, and valproate use were independently
      associated with increases in fasting glucose. However, hyperglycaemia and
      hypoglycaemic prescriptions were not more common in geriatric psychiatric
      patients. CONCLUSIONS: DM does not appear to be more common in geriatric
      psychiatric patients than similarly aged controls and is not more common in
      atypical AP users. However, depression and antidepressant, cholinesterase
      inhibitor, and valproate use may increase fasting glucose levels, and the
      clinical significance of this warrants further investigation. Nonetheless, given
      the rates of untreated and undertreated fasting hyperglycaemia in both our
      geriatric psychiatric and control samples (>10% of all patients), we recommend
      regular screening for DM in these populations.

PMID- 25369989
TI  - Cholinergic neurons of the basal forebrain mediate biochemical and
      electrophysiological mechanisms underlying sleep homeostasis.
AB  - The tight coordination of biochemical and electrophysiological mechanisms
      underlies the homeostatic sleep pressure (HSP) produced by sleep deprivation
      (SD). We have reported that during SD the levels of inducible nitric oxide
      synthase (iNOS), extracellular nitric oxide (NO), adenosine [AD]ex , lactate
      [Lac]ex and pyruvate [Pyr]ex increase in the basal forebrain (BF). However, it is
      not clear whether all of them contribute to HSP leading to increased
      electroencephalogram (EEG) delta activity during non-rapid eye movement (NREM)
      recovery sleep (RS) following SD. Previously, we showed that NREM delta increase
      evident during RS depends on the presence of BF cholinergic (ChBF) neurons. Here,
      we investigated the role of ChBF cells in coordination of biochemical and EEG
      changes seen during SD and RS in the rat. Increases in low-theta power (5-7 Hz),
      but not high-theta (7-9 Hz), during SD correlated with the increase in NREM delta
      power during RS, and with the changes in nitrate/nitrite [NOx ]ex and [AD]ex .
      Lesions of ChBF cells using IgG 192-saporin prevented increases in [NOx ]ex ,
      [AD]ex and low-theta activity, during SD, but did not prevent increases in
      [Lac]ex and [Pyr]ex . Infusion of NO donor DETA NONOate into the saporin-treated
      BF failed to increase NREM RS and delta power, suggesting ChBF cells are
      important for mediating NO homeostatic effects. Finally, SD-induced iNOS was
      mostly expressed in ChBF cells, and the intensity of iNOS induction correlated
      with the increase in low-theta activity. Together, our data indicate ChBF cells
      are important in regulating the biochemical and EEG mechanisms that contribute to
      HSP.

PMID- 25369992
TI  - Effects of denosumab, alendronate, or denosumab following alendronate on bone
      turnover, calcium homeostasis, bone mass and bone strength in ovariectomized
      cynomolgus monkeys.
AB  - Postmenopausal osteoporosis is a chronic disease wherein increased bone
      remodeling reduces bone mass and bone strength. Antiresorptive agents including
      bisphosphonates are commonly used to mitigate bone loss and fracture risk.
      Osteoclast inhibition via denosumab (DMAb), a RANKL inhibitor, is a newer
      approach for reducing fracture risk in patients at increased risk for fracture.
      The safety of transitioning from bisphosphonate therapy (alendronate; ALN) to
      DMAb was examined in mature ovariectomized (OVX) cynomolgus monkeys (cynos). One
      day after OVX, cynos (7-10/group) were treated with vehicle (VEH, s.c.), ALN (50
      MUg/kg, i.v., twice monthly) or DMAb (25 mg/kg/month, s.c.) for 12 months. Other
      animals received VEH or ALN for 6 months and then transitioned to 6 months of
      DMAb. DMAb caused significantly greater reductions in serum CTx than ALN, and
      transition from ALN to DMAb caused further reductions relative to continued ALN.
      DMAb and ALN decreased serum calcium (Ca), and transition from ALN to DMAb
      resulted in a lesser decline in Ca relative to DMAb or to VEH-DMAb transition.
      Bone histomorphometry indicated significantly reduced trabecular and cortical
      remodeling with DMAb or ALN. Compared with ALN, DMAb caused greater reductions in
      osteoclast surface, eroded surface, cortical porosity and fluorochrome labeling,
      and transition from ALN to DMAb reduced these parameters relative to continued
      ALN. Bone mineral density increased in all active treatment groups relative to
      VEH controls. Destructive biomechanical testing revealed significantly greater
      vertebral strength in all three groups receiving DMAb, including those receiving
      DMAb after ALN, relative to VEH controls. Bone mass and strength remained highly
      correlated in all groups at all tested skeletal sites, consistent with normal
      bone quality. These data indicate that cynos transitioned from ALN to DMAb
      exhibited reduced bone resorption and cortical porosity, and increased BMD and
      bone strength, without deleterious effects on Ca homeostasis or bone quality.

PMID- 25369991
TI  - microRNA-dependent temporal gene expression in the ureteric bud epithelium during
      mammalian kidney development.
AB  - BACKGROUND: Our previous study on mouse mutants with the ureteric bud (UB)
      epithelium-specific Dicer deletion (Dicer UB mutants) demonstrated the
      significance of UB epithelium-derived miRNAs in UB development. RESULTS: Our
      whole-genome transcriptional profiling showed that the Dicer mutant UB epithelium
      abnormally retained transcriptional features of the early UB epithelium and
      failed to express many genes associated with collecting duct differentiation.
      Furthermore, we identified a temporal expression pattern of early UB genes during
      UB epithelium development in which gene expression was detected at early
      developmental stages and became undetectable by embryonic day 14.5. In contrast,
      expression of early UB genes persisted at later stages in the Dicer mutant UB
      epithelium and increased at early stages. Our bioinformatic analysis of the
      abnormally persistently expressed early genes in the Dicer mutant UB epithelium
      showed significant enrichment of the let-7 family miRNA targets. We further
      identified a temporal expression pattern of let-7 miRNAs in the UB epithelium
      that is anti-parallel to that of some early UB genes during kidney development.
      CONCLUSIONS: We propose a model in which the let-7 family miRNAs silence the
      expression of a subset of early genes in the UB epithelium at later developmental
      stages to promote collecting duct differentiation. Developmental Dynamics 244:444
      456, 2015. (c) 2014 Wiley Periodicals, Inc.

PMID- 25369993
TI  - Fibrin ring granulomas in bone marrow in CMV infection.

PMID- 25369994
TI  - The cashmere connection, biodiversity, and climate: response to von Wehrden et
      al. 2014.

PMID- 25369995
TI  - WEDGE: an anticoagulant thrombin mutant produced by autoactivation.
AB  - BACKGROUND: The production of therapeutically relevant proteases typically
      involves activation of a zymogen precursor by external enzymes, which may raise
      regulatory issues about availability and purity. Recent studies of thrombin
      precursors have shown how to engineer constructs that spontaneously convert to
      the mature protease by autoactivation, without the need for external enzymes.
      OBJECTIVES: Autoactivation is an innovative strategy that promises to simplify
      the production of proteases of therapeutic relevance, but has not been tested in
      practical applications. The aim of this study was to provide a direct test of
      this strategy. METHODS: An autoactivating version of the thrombin mutant
      W215A/E217A (WE), which is currently in preclinical development as an
      anticoagulant, was engineered. RESULTS AND CONCLUSIONS: The autoactivating
      version of WE can be produced in large quantities, like WE made in BHK cells or
      Escherichia coli, and retains all significant functional properties in vitro and
      in vivo. The results serve as proof of principle that autoactivation is an
      innovative and effective strategy for the production of trypsin-like proteases of
      therapeutic relevance.

PMID- 25369997
TI  - NCD targets: from political to practical.

PMID- 25369996
TI  - Effects of prescription nonsteroidal antiinflammatory drugs on symptoms and
      disease progression among patients with knee osteoarthritis.
AB  - OBJECTIVE: The effect of short-term and long-term use of nonsteroidal
      antiinflammatory drugs (NSAIDs) on structural change is equivocal. The aim of
      this study was to estimate the extent to which short- and long-term use of
      prescription NSAIDs relieve symptoms and delay structural progression among
      patients with radiographically confirmed osteoarthritis (OA) of the knee.
      METHODS: We applied a new-user design among participants with confirmed OA not
      reporting NSAID use at the time of enrollment in the Osteoarthritis Initiative.
      Participants were evaluated for changes in the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) subscales (n = 1,846) and joint space
      width was measured using serial radiographs and a customized software tool (n =
      1,116) over 4 years. We used marginal structural modeling to estimate the effect
      of NSAIDs. RESULTS: Compared to participants who never reported prescription
      NSAID use, those reporting use at 1 or 2 assessments had no clinically important
      changes, but those reporting prescription NSAID use at all 3 assessments had, on
      average, 0.88 point improvement over the followup period (95% confidence interval
      [95% CI] -0.46 to 2.22) in pain, 0.72 point improvement (95% CI -0.12 to 1.56) in
      stiffness, and 4.27 points improvement (95% CI -0.31 to 8.84) in function. The
      average change in joint space width was 0.28 mm less among those reporting NSAID
      use at 3 assessments relative to nonusers (95% CI -0.06 to 0.62). Recent NSAID
      use findings were not clinically or statistically significant. CONCLUSION: Long
      term, but not short-term, NSAID use was associated with an a priori-defined
      minimally important clinical change in stiffness, physical function, and joint
      space width, but not pain. While showing modest clinical importance, the
      estimates did not reach statistical significance.

PMID- 25369998
TI  - Trends in the incidence of intensive care unit invasive mechanical ventilation
      and subsequent 2-year survival in very elderly New Zealanders.
AB  - BACKGROUND: The number of elderly in the general population is growing. There are
      therefore implications for the provision of intensive care unit (ICU) care to
      elderly patients. AIM: Our aim was to determine the incidence of ICU invasive
      mechanical ventilation (IMV), long-term outcomes of patients treated with IMV,
      and trends in these variables over a 10-year period in New Zealand, with a focus
      on very elderly patients (aged 80 years and over). METHODS: Analysis of New
      Zealand public hospital discharge data from July 1999 to June 2010, with linked
      long-term mortality data. Transfers or readmissions to different hospitals were
      linked using a national unique patient identifier. RESULTS: There were 58 003
      patients treated with IMV in a New Zealand ICU. Of these patients, 6.6% were very
      elderly. Population rates of ICU IMV declined or were static over all age groups.
      The 2-year mortality rate ranged from 15% in patients aged 16-39 years to 52% in
      the very elderly. The 2-year mortality rates for the very elderly were highest
      for acute medical patients (78%), followed by acute surgical admissions (46%) and
      elective admissions (35%). The 2-year mortality rate for all patients declined
      over the study period, and declined or was static for all age groups and
      admission types. In the very elderly, the standardised mortality ratio of
      patients surviving at 1 year who survived their second year after admission,
      compared with the age-matched general population, was lower than all other age
      groups. CONCLUSION: For very elderly patients over the period 1999-2009, the
      population rate of IMV was static and 2-year mortality declined.

PMID- 25370000
TI  - Visual scoring of coronary artery calcification in lung cancer screening computed
      tomography: association with all-cause and cardiovascular mortality risk.
AB  - OBJECTIVE: Current and former smokers are at an increased risk for lung cancer
      and cardiovascular disease (CVD). We investigated two methods of visual scoring
      of coronary artery calcium on lung cancer screening computed tomography (CT) to
      predict cardiovascular and all-cause mortality. PARTICIPANTS AND METHODS: Cases
      were 1000 participants, age 55-74 years, enrolled in the National Lung Screening
      Trial CT arm who died during the study. An equal number of participants alive at
      the end of the study (controls) were matched in terms of sex, CT scanner vendor,
      and model, and 5-year age and smoking pack-years group. Coronary calcium was
      measured visually by three readers using two semiquantitative scoring schemes.
      Conditional logistic regression was used to analyze the association between the
      presence and the extent of coronary calcium and all-cause and cardiovascular
      mortality, stratified on matching criteria. RESULTS: Cases and controls were well
      matched for age (64+/-6 vs. 64+/-5, P=0.95) and mean pack-years smoking (61+/-24
      vs. 62+/-24, P=1.0). Cases were significantly more likely to have coronary
      calcium than controls (85 vs. 77%, P<0.001). Having any calcium was associated
      with an increased risk for CVD mortality using either visual scoring method (odds
      ratio 3.4, 95% confidence interval 2.0-5.6, P<0.001, and odds ratio 3.3, 95%
      confidence interval 2.0-5.6, P<0.001). CONCLUSION: Visual scoring of coronary
      calcium predicts all-cause and CVD mortality in National Lung Screening Trial
      participants, independent of current versus former smoking status. Visual
      coronary calcium scoring in low-dose CT scans helps identify individuals at high
      risk for mortality who may benefit from further CVD prevention.

PMID- 25369999
TI  - Antioxidants and coronary artery disease: from pathophysiology to preventive
      therapy.
AB  - Oxidant stress in the cardiovascular system may occur when antioxidant capacity
      is insufficient to reduce reactive oxygen species and other free radicals.
      Oxidant stress has been linked to the pathogenesis of atherosclerosis and
      incident coronary artery disease. As a result of this connection, early
      observational studies focused on dietary antioxidants, such as beta-carotene,
      alpha-tocopherol, and ascorbic acid, and demonstrated an inverse relationship
      between intake of these antioxidants and major adverse cardiovascular events.
      These findings supported a number of randomized trials on the use of selected
      antioxidants as primary or secondary prevention strategies to decrease cardiac
      risk; however, many of these studies reported disappointing results with little
      or no observed risk reduction in antioxidant-treated patients. Several plausible
      explanations for these findings have been suggested, including incorrect
      antioxidant choice or dose, synthetic versus dietary antioxidants as the
      intervention, and patient selection, all of which will be important to consider
      when designing future clinical trials. This review will focus on the contemporary
      evidence that is the basis for our current understanding of the role of
      antioxidants in cardiovascular disease prevention. 

PMID- 25370001
TI  - Inappropriate left ventricular mass and poor outcomes in patients with angina
      pectoris and normal ejection fraction.
AB  - OBJECTIVES: Although inappropriate left ventricular mass has been associated with
      clustered cardiac geometric and functional abnormalities, its predictive value in
      patients with coronary artery disease is still unknown. This study examined the
      association of inappropriate left ventricular mass with clinical outcomes in
      patients with angina pectoris and normal ejection fraction. PARTICIPANTS AND
      METHODS: Consecutive patients diagnosed with angina pectoris whose ejection
      fraction was normal were recruited from 2008 to 2012. Inappropriate left
      ventricular mass was determined when the ratio of actual left ventricular mass to
      the predicted one exceeded 150%. The primary endpoint was a composite of all
      cause death, nonfatal myocardial infarction, and nonfatal stroke. Clinical
      outcomes between the inappropriate and appropriate left ventricular mass group
      were compared before and after propensity matching. RESULTS: Of the total of 1515
      participants, 18.3% had inappropriate left ventricular mass. Patients with
      inappropriate left ventricular mass had a higher composite event rate compared
      with those with appropriate left ventricular mass (11.2 vs. 6.6%, P=0.010).
      Multivariate Cox regression analyses showed that inappropriate left ventricular
      mass was an independent risk factor for adverse events (adjusted hazard ratio,
      1.59; 95% confidence interval, 1.03-2.45; P=0.035). The worse outcome in patients
      with inappropriate left ventricular mass was further validated in a propensity
      matching cohort and patients with the traditional definition of left ventricular
      hypertrophy. CONCLUSION: Inappropriate left ventricular mass was associated with
      an increased risk of adverse events in patients with angina pectoris and normal
      ejection fraction.

PMID- 25370002
TI  - Quality improvement in acute coronary syndromes: translating evidence into
      practice.
AB  - Despite the substantial progress in elucidating the pathophysiology of acute
      coronary syndromes (ACS) and developing an array of therapeutic advances for the
      management of these conditions, several challenges still persist. The use of
      guideline recommendations for the care of patients with ACS by both healthcare
      providers and hospitals can improve short-term and long-term outcomes and
      potentially reduce healthcare costs. However, evidence suggests that adherence to
      guidelines is suboptimal. Several quality improvement programs, by both
      governmental and nongovernmental organizations, have been developed in an attempt
      to encourage maximal utilization of evidence-based interventions. In this review,
      we will examine the evidence for the importance of guideline adherence in the
      management of ACS, explore predictors of adherence to these guidelines, and
      provide evidence-based strategies for improving their implementation. 

PMID- 25370004
TI  - Protection of cultured human hepatocytes from hydrogen peroxide-induced apoptosis
      by relaxin-3.
AB  - Previous studies have suggested that hepatocyte apoptosis may be a fundamental
      underlying mechanism of liver injury and diseases, such as liver fibrosis.
      Relaxin-3 has been reported to have anti-fibrotic actions in the heart and to
      attenuate isoproterenol-induced myocardial injury; however, the beneficial role
      of relaxin-3 on hepatocyte apoptosis remains to be elucidated. The aim of the
      present study was to explore the role and possible mechanisms of relaxin-3
      through hydrogen peroxide (H2O2)-induced apoptosis in primary human hepatocytes.
      Cells were treated with relaxin-3 and then cell viability, morphological
      features, the presence of cleaved caspases as well as the levels of endoplasmic
      reticulum stress (ERS) protein markers and autophagy markers were evaluated. The
      H2O2 group showed significantly decreased cell viability, increased apoptosis as
      well as upregulation of caspases (cleaved caspase-3, -8 and -9) and ERS protein
      markers compared with those of the control group. However, cells treated with
      relaxin-3 (10 ng/ml) demonstrated improved cell viability, reduced apoptosis and
      decreased expression of cleaved caspases and ERS markers. However, the expression
      of autophagy markers remained unchanged following H2O2-induced apoptosis and
      relaxin-3 treatment. In conclusion, relaxin-3 was shown to protect hepatocytes
      from H2O2-induced apoptosis via downregulation of cleaved caspase-8 and -9, as
      well as inhibition of the ERS pathway. 

PMID- 25370005
TI  - People's Perceptions and Beliefs about their Ability to Exercise with Rheumatoid
      Arthritis: A Qualitative Study.

PMID- 25370003
TI  - Clinical pattern and spectrum of endometrial pathologies in patients with
      abnormal uterine bleeding in Pakistan: need to adopt a more conservative approach
      to treatment.
AB  - BACKGROUND: Abnormal uterine bleeding (AUB) is one of the most common
      debilitating menstrual problems and has remained one of the most frequent
      indications for hysterectomy in developing countries. Approximately in 40% of
      hysterectomy specimens, no definite organic pathology could be established. The
      problem is common worldwide but causes may vary from one region to another. This
      study may help gynecologists in our population to improve their therapeutic
      strategies by promoting minimally invasive uterus sparing modalities such as
      endometrial ablation and hysteroscopic resection of early proliferative lesions.
      METHODS: It was a prospective, cross-sectional study conducted at Liaquat
      National Hospital from 15(th) January 2010 till 14(th) July 2011 over a period of
      18 months. Women who underwent dilatation and curettage for endometrial sampling
      with complaints of AUB were included in the study and histopathologic spectrum
      was determined. RESULTS: Polymenorrhea was the most common presenting pattern
      (30%, 72/241) with reproductive age women being the most susceptible
      (49.3%,119/241). The commonest histopathological spectrum was normal menstrual
      pattern (34%, 82/241) and the commonest pathology was hormonal imbalance (27%,
      65/241), followed by endometrial polyp (14%, 34/241), chronic endometritis (12%,
      28/241), atrophic endometrium (6%, 15/241), endometrial hyperplasia (5%, 12/241),
      and endometrial carcinoma (2%, 5/241). Chronic endometritis was commonly seen in
      reproductive age (18%, 21/119); hormonal imbalance (45%, 35/77) and endometrial
      hyperplasia (6.5%, 5/77) in perimenopausal age; endometrial polyp (35.5%, 16/45)
      and endometrial carcinoma (9%, 4/45) in postmenopausal age. CONCLUSION: Frequency
      of benign endometrial pathology is quite high in AUB, 236 participants (98%,
      236/241). Histopathological spectrum in patients with AUB is quite variable with
      respect to age. The most common pattern of AUB was polymenorrhea. The most common
      pathology was hormonal imbalance. It is suggested that age was associated with
      more progressive lesions found in peri and postmenopausal age group such as
      endometrial hyperplasia and endometrial carcinoma. Yet endometrial polyp was the
      most common pathology found in postmenopausal women. Therefore, the management
      strategy should be individualized, as in most cases a restrictive approach is
      appropriate in order to avoid unnecessary hysterectomies.

PMID- 25370006
TI  - Oestrus synchronization treatment induces histomorphological changes on the
      uterine tube epithelium of the gilt.
AB  - The aim of this study was to determine the histomorphological changes that
      occurred in response to two treatments for oestrus synchronization in three
      different regions of the gilt's uterine tubes epithelium: the ampulla (AMP),
      ampulla-isthmic junction (AIJ) and isthmus (IST). Nine prepuberal gilts were
      divided into three groups (n = 3): (1) eCG 400 IU and hCG 200 IU (eCG/hCG), (2)
      progesterone agonist (P4) and (3) control group. The number of secretory cells
      (stained with periodic acid-Schiff reaction or PAS-positive cells) decreased in
      the AMP in the P4 treated group when compared to the control group, whereas, no
      difference was observed in the number of PAS-negative cells in the AMP of the
      three groups. A significant decrease in the number of PAS-positive cells was
      observed in the AIJ and IST of the P4 treated group when compared to the eCG/hCG
      and control groups. An increase in the number of PAS-negative cells was observed
      in the AIJ and IST in the P4 treated group. The epithelium height in the AMP and
      AIJ was increased in the eCG/hCG group when compared to the control and P4
      groups. In this last group, we observed a reduced height compared with the other
      two groups for the AIJ. In the IST, there were no significant changes in the
      epithelium height of the control or the other two groups (eCG/hCG and P4). The
      epithelial cells of the P4 treated group had the least amount of cytoplasmic
      granules and the lowest intensity of PAS staining in the AMP, AIJ and IST.
      Animals treated with eCG/hCG showed an intermediate number of cytoplasmic
      granules and intensity in all regions evaluated. These data show that P4
      treatment for synchronization induces a significant (P < 0.001) decrease of PAS
      positive cells and staining intensity of cytoplasmic granules in the different
      regions studied and an increased number of PAS-negative cells in the AIJ and IST
      epithelium. Moreover, eCG/hCG treatment increased the height of the epithelium in
      the AMP and AIJ, while in this last region, the P4 treatment decreased the
      epithelium height. These results show that synchronization treatments with P4 and
      in a smaller proportion with eCG/hCG can modify the amount of PAS-positive and
      PAS-negative cells, and the epithelium height. This has influence in the
      secretory activity of the epithelium and possibly alters the fluid
      microenvironment of the gilt's uterine tube. The biological impact of regional
      variations in the epithelial cells of the gilt's uterine tube needs further
      investigation to understand the implications that the reproductive processes can
      have in the uterine tube. 

PMID- 25370007
TI  - A Longitudinal Multilevel Study of Individual Characteristics and Classroom Norms
      in Explaining Bullying Behaviors.
AB  - This three-wave longitudinal study was set out to examine the interplay between
      individual characteristics (social standing in the classroom) and descriptive and
      injunctive classroom norms (behavior and attitudes, respectively) in explaining
      subsequent bullying behavior, defined as initiating, assisting, or reinforcing
      bullying. The target sample contained fourth- to sixth-grade students (n = 2,051)
      who attended the control schools in the Finnish evaluation of the KiVa
      antibullying program. Random slope multilevel analyses revealed that, over time,
      higher popularity or rejection, or lower acceptance were associated with
      increases in bullying behaviors, especially in classrooms with a high descriptive
      bullying norm. In contrast, the injunctive norm did not moderate the associations
      between social standing and engagement in bullying, except for children high on
      popularity. Theoretical and practical implications of the results are discussed.

PMID- 25370009
TI  - Interaction of perfluoroalkyl acids with human liver fatty acid-binding protein.
AB  - Perfluoroalkyl acids (PFAAs) are highly persistent and bioaccumulative, resulting
      in their broad distribution in humans and the environment. The liver is an
      important target for PFAAs, but the mechanisms behind PFAAs interaction with
      hepatocyte proteins remain poorly understood. We characterized the binding of
      PFAAs to human liver fatty acid-binding protein (hL-FABP) and identified critical
      structural features in their interaction. The binding interaction of PFAAs with
      hL-FABP was determined by fluorescence displacement and isothermal titration
      calorimetry (ITC) assay. Molecular simulation was conducted to define
      interactions at the binding sites. ITC measurement revealed that PFOA/PFNA
      displayed a moderate affinity for hL-FABP at a 1:1 molar ratio, a weak binding
      affinity for PFHxS and no binding for PFHxA. Moreover, the interaction was mainly
      mediated by electrostatic attraction and hydrogen bonding. Substitution of Asn111
      with Asp caused loss of binding affinity to PFAA, indicating its crucial role for
      the initial PFAA binding to the outer binding site. Substitution of Arg122 with
      Gly caused only one molecule of PFAA to bind to hL-FABP. Molecular simulation
      showed that substitution of Arg122 increased the volume of the outer binding
      pocket, making it impossible to form intensive hydrophobic stacking and hydrogen
      bonds with PFOA, and highlighting its crucial role in the binding process. The
      binding affinity of PFAAs increased significantly with their carbon number.
      Arg122 and Asn111 played a pivotal role in these interactions. Our findings may
      help understand the distribution pattern, bioaccumulation, elimination, and
      toxicity of PFAAs in humans. 

PMID- 25370010
TI  - Bioactivation of food genotoxicants 5-hydroxymethylfurfural and furfuryl alcohol
      by sulfotransferases from human, mouse and rat: a comparative study.
AB  - 5-Hydroxymethylfurfural (HMF) and furfuryl alcohol (FFA) are moderately potent
      rodent carcinogens that are present in thermally processed foodstuffs. The
      carcinogenic effects were hypothesized to originate from sulfotransferase (SULT)
      mediated bioactivation yielding DNA-reactive and mutagenic sulfate esters, a
      confirmed metabolic pathway of HMF and FFA in mice. It is known that orthologous
      SULT forms substantially differ in substrate specificity and tissue distribution.
      This could influence HMF- and FFA-induced carcinogenic effects. Here, we studied
      HMF and FFA sulfoconjugation by 30 individual SULT forms of humans, mice and
      rats. The catalytic efficiencies (k cat/K M) of HMF sulfoconjugation of human
      SULT1A1 (13.7 s(-1) M(-1)), mouse Sult1a1 (15.8 s(-1) M(-1)) and 1d1 (4.8 s(-1)
      M(-1)) and rat Sult1a1 (5.3 s(-1) M(-1)) were considerably higher than those of
      all other SULT forms investigated (<=0.73 s(-1 )M(-1)). FFA sulfoconjugation was
      monitored using adenosine as a nucleophilic scavenger for the reactive 2
      sulfoxymethylfuran (t 1/2 = 20 s at 37  degrees C). The resulting adduct N (6)
      ((furan-2-yl)methyl)-adenosine (N (6)-MF-A) was quantified by isotope-dilution
      UPLC-MS/MS. The rates of N (6)-MF-A formation showed that hSULT1A1 and its
      orthologues in mice and rats were also the most important contributors to FFA
      sulfoconjugation in each of the species. Taken together, the catalytic capacity
      of hSULT1A1 is comparable to that of mSult1a1 in mice, the species in which
      carcinogenic effects of HMF and FFA were detected. This is of primary concern due
      to the expression of hSULT1A1 in many different tissues. 

PMID- 25370011
TI  - Role of brain cytochrome P450 mono-oxygenases in bilirubin oxidation-specific
      induction and activity.
AB  - In the Crigler-Najjar type I syndrome, the genetic absence of efficient hepatic
      glucuronidation of unconjugated bilirubin (UCB) by the uridine 5'-diphospho
      glucuronosyltransferase1A1 (UGT1A1) enzyme produces the rise of UCB level in
      blood. Its entry to central nervous system could generate toxicity and
      neurological damage, and even death. In the past years, a compensatory mechanism
      to liver glucuronidation has been indicated in the hepatic cytochromes P450
      enzymes (Cyps) which are able to oxidize bilirubin. Cyps are expressed also in
      the central nervous system, the target of bilirubin toxicity, thus making them
      theoretically important to confer a protective activity toward bilirubin
      accumulation and neurotoxicity. We therefore investigated the functional
      induction (mRNA, EROD/MROD) and the ability to oxidize bilirubin of Cyp1A1, 1A2,
      and 2A3 in primary astrocytes cultures obtained from two rat brain region
      (cortex: Cx and cerebellum: Cll). We observed that Cyp1A1 was the Cyp isoform
      more easily induced by beta-naphtoflavone (betaNF) in both Cx and Cll astrocytes,
      but oxidized bilirubin only after uncoupling by 3, 4,3',4'-tetrachlorobiphenyl
      (TCB). On the contrary, Cyp1A2 was the most active Cyp in bilirubin clearance
      without uncoupling, but its induction was confined only in Cx cells. Brain Cyp2A3
      was not inducible. In conclusion, the exposure of astrocytes to betaNF plus TCB
      significantly enhanced Cyp1A1 mediating bilirubin clearance, improving cell
      viability in both regions. These results may be a relevant groundwork for the
      manipulation of brain Cyps as a therapeutic approach in reducing bilirubin
      induced neurological damage. 

PMID- 25370012
TI  - Replica to K. Takeda et al. Commentary to Pastore et al. (2014): epidermal growth
      factor receptor signalling in keratinocyte biology: implications for skin
      toxicity of tyrosine kinase inhibitors.

PMID- 25370008
TI  - Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man,
      and in human skin models.
AB  - The exposure of the skin to medical drugs, skin care products, cosmetics, and
      other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in
      the skin highly interesting. Since the use of freshly excised human skin for
      experimental investigations meets with ethical and practical limitations,
      information on XME in models comes in the focus including non-human mammalian
      species and in vitro skin models. This review attempts to summarize the
      information available in the open scientific literature on XME in the skin of
      human, rat, mouse, guinea pig, and pig as well as human primary skin cells, human
      cell lines, and reconstructed human skin models. The most salient outcome is that
      much more research on cutaneous XME is needed for solid metabolism-dependent
      efficacy and safety predictions, and the cutaneous metabolism comparisons have to
      be viewed with caution. Keeping this fully in mind at least with respect to some
      cutaneous XME, some models may tentatively be considered to approximate
      reasonable closeness to human skin. For dermal absorption and for skin irritation
      among many contributing XME, esterase activity is of special importance, which in
      pig skin, some human cell lines, and reconstructed skin models appears reasonably
      close to human skin. With respect to genotoxicity and sensitization, activating
      XME are not yet judgeable, but reactive metabolite-reducing XME in primary human
      keratinocytes and several reconstructed human skin models appear reasonably close
      to human skin. For a more detailed delineation and discussion of the severe
      limitations see the "Overview and Conclusions" section in the end of this review.

PMID- 25370013
TI  - In vitro systems: current limitations and future perspectives.

PMID- 25370014
TI  - FluG affects secretion in colonies of Aspergillus niger.
AB  - Colonies of Aspergillus niger are characterized by zonal heterogeneity in growth,
      sporulation, gene expression and secretion. For instance, the glucoamylase gene
      glaA is more highly expressed at the periphery of colonies when compared to the
      center. As a consequence, its encoded protein GlaA is mainly secreted at the
      outer part of the colony. Here, multiple copies of amyR were introduced in A.
      niger. Most transformants over-expressing this regulatory gene of amylolytic
      genes still displayed heterogeneous glaA expression and GlaA secretion. However,
      heterogeneity was abolished in transformant UU-A001.13 by expressing glaA and
      secreting GlaA throughout the mycelium. Sequencing the genome of UU-A001.13
      revealed that transformation had been accompanied by deletion of part of the fluG
      gene and disrupting its 3' end by integration of a transformation vector.
      Inactivation of fluG in the wild-type background of A. niger also resulted in
      breakdown of starch under the whole colony. Asexual development of the ?fluG
      strain was not affected, unlike what was previously shown in Aspergillus
      nidulans. Genes encoding proteins with a signal sequence for secretion, including
      part of the amylolytic genes, were more often downregulated in the central zone
      of maltose-grown ?fluG colonies and upregulated in the intermediate part and
      periphery when compared to the wild-type. Together, these data indicate that FluG
      of A. niger is a repressor of secretion. 

PMID- 25370015
TI  - The relationship of the whole genome sequence identity to DNA hybridization
      varies between genera of prokaryotes.
AB  - In the original proposal of Wayne et al. (Int J Syst Bacteriol 37:463-464, 1987),
      two measures of genetic relatedness were proposed to set the boundary for
      prokaryotic species. The first was the change in the melting temperature
      (DeltaTm) of heteroduplex DNA and the second was the extent of DNA-DNA
      hybridization (DDH). While this approach was justified given the experimental
      error inherent in these methods, genomic sequencing has the potential to measure
      both parameters with great precision. The average nucleotide identity (ANIb), a
      surrogate for the DeltaTm, and the calculated DDH (cDDH) were determined from the
      complete genomes of representatives of 17 genera of prokaryotes. When the ANIb
      was >75 %, the ratio (100-cDDH)/(100-ANIb) was 3.69 +/- 0.93 (+/- SD) and varied
      from about 2.35 to 4.59 between genera. The differences among genera was highly
      significant (p < 0.001) but not correlated with specific phylogenetic or
      physiological groups. Moreover, the ANIm was a poor measure of ANIb when ANIb was
      <75 %. Because the ANIb and cDDH provide different measures of relatedness, it is
      no longer appropiate to consider both when delineating species. For these
      reasons, measures of relatedness based upon sequence identity should be used for
      delineating species in the future. 

PMID- 25370016
TI  - 'Millia-like cysts on an erythematous background': dermoscopic features of
      keratoacanthoma en plaque.

PMID- 25370017
TI  - Comorbid anxiety disorders in late-life depression: results of a cohort study.
AB  - BACKGROUND: Comorbid anxiety disorders are common in late-life depression and
      negatively impact treatment outcome. This study aimed to examine personality
      characteristics as well as early and recent life-events as possible determinants
      of comorbid anxiety disorders in late-life depression, taking previously examined
      determinants into account. METHODS: Using the Composite International Diagnostic
      Interview (CIDI 2.0), we established comorbid anxiety disorders (social phobia
      (SP), panic disorder (PD), generalized anxiety disorder (GAD), and agoraphobia
      (AGO)) in 350 patients (aged >=60 years) suffering from a major depressive
      disorder according to DSM-IV-TR criteria within the past six months. Adjusted for
      age, sex, and level of education, we first examined previously identified
      determinants of anxious depression: depression severity, suicidality, partner
      status, loneliness, chronic diseases, and gait speed in multiple logistic
      regression models. Subsequently, associations were explored with the big five
      personality characteristics as well as early and recent life-events. First,
      multiple logistic regression analyses were conducted with the presence of any
      anxiety disorder (yes/no) as dependent variable, where after analyses were
      repeated for each anxiety disorder, separately. RESULTS: In our sample, the
      prevalence rate of comorbid anxiety disorders in late-life depression was 38.6%.
      Determinants of comorbid anxiety disorders were a lower age, female sex, less
      education, higher depression severity, early traumatization, neuroticism,
      extraversion, and conscientiousness. Nonetheless, determinants differed across
      the specific anxiety disorders and lumping all anxiety disorder together masked
      some determinants (education, personality). CONCLUSIONS: Our findings stress the
      need to examine determinants of comorbid anxiety disorder for specific anxiety
      disorders separately, enabling the development of targeted interventions within
      subgroups of depressed patients.

PMID- 25370018
TI  - A note of caution on the diagnosis of Martin-Probst syndrome by the detection of
      the p.D59G mutation in the RAB40AL gene.
AB  - Martin-Probst syndrome (MPS) is an X-linked multisystem neurodevelopmental
      disorder, reported to be caused by the p.D59G mutation in RAB40AL. Whereas
      evidence against the pathogenic role of p.D59G has been published, the presence
      of RAB40AL p.D59G continues to be used as a support for MPS diagnosis. Our
      purpose was to provide further arguments for excluding pathogenicity of RAB40AL
      p.D59G. We detected p.D59G in two healthy males ascertained as family members of
      p.D59G carriers who underwent whole exome sequencing for diagnostic reasons.
      Furthermore, we found that p.D59G was present in 2.86% (4/140) of randomly
      selected Polish males with higher education. CONCLUSION: Our findings are
      inconsistent with a causative effect of RAB40AL p.D59G on cognitive impairment
      combined with severe to profound bilateral hearing loss but indicate that p.D59G
      is a common genetic variation. Our data emphasize the need for genotyping large
      sample sizes of diverse populations as a basic tool in determining variant
      pathogenicity.

PMID- 25370020
TI  - Taking good care of myself: a qualitative study on self-care behavior among
      Chinese persons with a permanent colostomy.
AB  - In Chinese culture, as a possible consequence of Confucianism, caring for the
      sick is considered a moral obligation of family members, while self-care is only
      the basis of fulfilling filial piety. This qualitative study aims to explore the
      self-care behavior among persons with a permanent colostomy in a Chinese cultural
      context of emphasizing the role of family caregiving. Data from in-depth
      interviews with seven Chinese adults at a university hospital in southwest China
      were analyzed using content analysis. Informants' self-care behavior was
      characterized by "taking good care of myself," which underlined individuals'
      efforts to manage colostomy-related impacts involving: (i) taking care of my
      colostomy with a proper degree of independence; (ii) taking care of my life by
      dealing with limitations; (iii) taking care of my mood in a positive way.
      Findings revealed that informants' self-care behavior was linked to their
      Confucian beliefs in family obligations, and also influenced by a happy-go-lucky
      outlook of life, a likely product of Taoism. The information is useful for nurses
      to design a culturally appropriate care plan to improve self-care behavior and
      proper family caregiving. 

PMID- 25370019
TI  - Postoperative medical complications associated with anesthesia in older adults
      with dementia.
AB  - OBJECTIVES: To examine the association between anesthetic technique and
      postoperative complications in older adults with dementia undergoing hip fracture
      surgery. DESIGN: Population-based, retrospective cohort study. SETTING: Ontario,
      Canada. PARTICIPANTS: All older adults with dementia who underwent surgery for
      hip fracture repair in Ontario, Canada, between April 1, 2003 and March 31, 2011.
      MEASUREMENTS: The baseline characteristics of individuals who received general
      anesthesia (GA) and regional anesthesia (RA) were compared. Individuals who
      received GA were matched to similar individuals who received RA using propensity
      scores to control for confounding, and their outcomes compared, including 30-day
      mortality, intensive care unit (ICU) admissions, specific postoperative medical
      complications, and hospital length of stay (LOS). RESULTS: In the 6,135 matched
      pairs, there was no statistically significant difference in postoperative 30-day
      mortality (GA, 11.3%; RA, 10.8%, P = .44). There were no statistically
      significant differences in the rates of specific postoperative medical
      complications or LOS in the two anesthetic groups, but GA was associated with
      higher rates of ICU admissions (6.1% vs 4.2%, P < .001). CONCLUSION: For older
      adults with dementia undergoing hip fracture surgery, GA and RA are associated
      with similar rates of most perioperative adverse events. Further studies are
      required to determine the optimal methods of providing anesthesia and
      perioperative care for older adults with dementia undergoing surgical procedures.

PMID- 25370021
TI  - Strongly coupled cyclometalated ruthenium-triarylamine hybrids: tuning
      electrochemical properties, intervalence charge transfer, and spin distribution
      by substituent effects.
AB  - Nine cyclometalated ruthenium complexes with a redox-active diphenylamine unit in
      the para position to the Ru?C bond were prepared. MeO, Me, and Cl substituents on
      the diphenylamine unit and three types of auxiliary ligands-bis(N
      methylbenzimidazolyl)pyridine (Mebip), 2,2':6',2''-terpyridine (tpy), and
      trimethyl-4,4',4''-tricarboxylate-2,2':6',2''-terpyridine (Me3 tctpy)--were used
      to vary the electronic properties of these complexes. The derivative with an MeO
      substituted amine unit and Me3 tctpy ligand was studied by single-crystal X-ray
      analysis. All complexes display two well-separated redox waves in the potential
      region of +0.1 to +1.0 V versus Ag/AgCl, and the potential splitting ranges from
      360 to 510 mV. Spectroelectrochemical measurements show that these complexes
      display electrochromism at low potentials and intense near-infrared (NIR)
      absorptions. In the one-electron oxidized form, the complex with the Cl
      substituted amine unit and Mebip ligand shows a moderate ligand-to-metal charge
      transfer at 800 nm. The other eight complexes show asymmetric, narrow, and
      intense intervalence charge-transfer transitions in the NIR region, which are
      independent of the polarity of the solvent. The Mebip-containing complexes
      display rhombic or broad isotropic EPR signals, whereas the other seven complexes
      show relatively narrow isotropic EPR signals. In addition, DFT and time-dependent
      DFT studies were performed to gain insights into the spin distributions and NIR
      absorptions.

PMID- 25370022
TI  - A study on the impact of hydroxypropyl methylcellulose on the viscosity of PEG
      melt suspensions using surface plots and principal component analysis.
AB  - An understanding of the rheological behaviour of polymer melt suspensions is
      crucial in pharmaceutical manufacturing, especially when processed by spray
      congealing or melt extruding. However, a detailed comparison of the viscosities
      at each and every temperature and concentration between the various grades of
      adjuvants in the formulation will be tedious and time-consuming. Therefore, the
      statistical method, principal component analysis (PCA), was explored in this
      study. The composite formulations comprising polyethylene glycol (PEG) 3350 and
      hydroxypropyl methylcellulose (HPMC) of ten different grades (K100 LV, K4M, K15M,
      K100M, E15 LV, E50 LV, E4M, F50 LV, F4M and Methocel VLV) at various
      concentrations were prepared and their viscosities at different temperatures
      determined. Surface plots showed that concentration of HPMC had a greater effect
      on the viscosity compared to temperature. Particle size and size distribution of
      HPMC played an important role in the viscosity of melt suspensions. Smaller
      particles led to a greater viscosity than larger particles. PCA was used to
      evaluate formulations of different viscosities. The complex viscosity profiles of
      the various formulations containing HPMC were successfully classified into three
      clusters of low, moderate and high viscosity. Formulations within each group
      showed similar viscosities despite differences in grade or concentration of HPMC.
      Formulations in the low viscosity cluster were found to be sprayable. PCA was
      able to differentiate the complex viscosity profiles of different formulations
      containing HPMC in an efficient and time-saving manner and provided an excellent
      visualisation of the data.

PMID- 25370023
TI  - Potential of Piperazinylalkylester Prodrugs of 6-Methoxy-2-Naphthylacetic Acid (6
      MNA) for Percutaneous Drug Delivery.
AB  - Piperazinylalkyl ester prodrugs (4a-5d) of 6-methoxy-2-naphthylacetic acid (6
      MNA) (1) were synthesized and evaluated in vitro for the purpose of percutaneous
      drug delivery. These ionizable prodrugs exhibited varying aqueous solubilities
      and lipophilicities depending on the pH of the medium. The prodrugs (4a-5c)
      showed higher aqueous solubility and similar lipophilicity at pH 5.0 and lower
      aqueous solubility and higher lipophilicity at pH 7.4 in comparison to 6-MNA. The
      chemical and enzymatic hydrolyses of the prodrugs was investigated in aqueous
      buffer solutions (pH 5.0 and 7.4) and in 80% human serum (pH 7.4) at 37 degrees
      C. The prodrugs showed moderate chemical stability (t 1/2 = 6-60 h) but got
      readily hydrolyzed enzymatically to 6-MNA with half-life ranging from 10-60 min.
      In the in vitro permeation study using rat skin, the flux of 6-MNA and the
      prodrugs was determined in aqueous buffers of pH 5.0 and 7.4. The prodrug (5b)
      showed 7.9- and 11.2-fold enhancement in skin permeation compared to 6-MNA (1) at
      pH 5.0 and 7.4, respectively. It was concluded that the parent NSAIDs having
      favorable pharmacokinetic and pharmacodynamic properties coupled with increased
      skin permeability of their prodrugs could give better options for the treatment
      of rheumatic diseases. 

PMID- 25370025
TI  - Lyophilized sustained release mucoadhesive chitosan sponges for buccal buspirone
      hydrochloride delivery: formulation and in vitro evaluation.
AB  - This work aims to prepare sustained release buccal mucoadhesive lyophilized
      chitosan sponges of buspirone hydrochloride (BH) to improve its systemic
      bioavailability. Chitosan sponges were prepared using simple casting/freeze
      drying technique according to 3(2) factorial design where chitosan grade was set
      at three levels (low, medium, and high molecular weight), and concentration of
      chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo
      mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of
      50% BH (T50%) were chosen as dependent variables. Additional BH cup and core
      buccal chitosan sponge were prepared to achieve uni-directional BH release toward
      the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH,
      scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo
      mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were
      able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and
      exhibited a uni-directional drug release profile following Higuchi diffusion
      model. 

PMID- 25370024
TI  - Characterization and comparison of lidocaine-tetracaine and lidocaine-camphor
      eutectic mixtures based on their crystallization and hydrogen-bonding abilities.
AB  - Eutectic mixtures formed between active pharmaceutical ingredients and/or
      excipients provide vast scope for pharmaceutical applications. This study aimed
      at the exploration of the crystallization abilities of two eutectic mixtures (EM)
      i.e., lidocaine-tetracaine and lidocaine-camphor (1:1 w/w). Thermogravimetric
      analysis (TGA) for degradation behavior whereas modulated temperature
      differential scanning calorimetry (MTDSC) set in first heating, cooling, and
      second heating cycles, was used to qualitatively analyze the complex exothermic
      and endothermic thermal transitions. Raman microspectroscopy characterized
      vibrational information specific to chemical bonds. Prepared EMs were left at
      room temperature for 24 h to visually examine their crystallization potentials.
      The degradation of lidocaine, tetracaine, camphor, lidocaine-tetracaine EM, and
      lidocaine-camphor EM began at 196.56, 163.82, 76.86, 146.01, and 42.72 degrees C,
      respectively, which indicated that eutectic mixtures are less thermostable
      compared to their individual components. The MTDSC showed crystallization peaks
      for lidocaine, tetracaine, and camphor at 31.86, 29.36, and 174.02 degrees C,
      respectively (n = 3). When studying the eutectic mixture, no crystallization peak
      was observed in the lidocaine-tetracaine EM, but a lidocaine-camphor EM
      crystallization peak was present at 18.81 degrees C. Crystallization occurred in
      lidocaine-camphor EM after being kept at room temperature for 24 h, but not in
      lidocaine-tetracaine EM. Certain peak shifts were observed in Raman spectra which
      indicated possible interactions of eutectic mixture components, when a eutectic
      mixture was formed. We found that if the components forming a eutectic mixture
      have crystallization peaks close to each other and have sufficient hydrogen
      bonding capability, then their eutectic mixture is least likely to crystallize
      out (as seen in lidocaine-tetracaine EM) or vice versa (lidocaine-camphor EM). 

PMID- 25370026
TI  - Letter from the New Editor-in-Chief.
AB  - It is my great pleasure to serve as the new Editor-in-Chief of Life, a journal
      concerned with fundamental questions on the origins and nature of life, evolution
      of biosystems and astrobiology. With my experience as Executive Editor, Senior
      Editor and Guest Editor of so many successful special issues (some of them in
      MDPI journals [1-6]), I am committed to making the journal a success, with the
      launch of exciting special issues, publication of high quality papers, as well as
      inclusion of the journal in major indexing and abstracting services. In this
      editorial, I present my view and plans for the journal. [...]. 

PMID- 25370027
TI  - The formation of jupiter, the jovian early bombardment and the delivery of water
      to the asteroid belt: the case of (4) vesta.
AB  - The asteroid (4) Vesta, parent body of the Howardite-Eucrite-Diogenite
      meteorites, is one of the first bodies that formed, mostly from volatile-depleted
      material, in the Solar System. The Dawn mission recently provided evidence that
      hydrated material was delivered to Vesta, possibly in a continuous way, over the
      last 4 Ga, while the study of the eucritic meteorites revealed a few samples that
      crystallized in presence of water and volatile elements. The formation of Jupiter
      and probably its migration occurred in the period when eucrites crystallized, and
      triggered a phase of bombardment that caused icy planetesimals to cross the
      asteroid belt. In this work, we study the flux of icy planetesimals on Vesta
      during the Jovian Early Bombardment and, using hydrodynamic simulations, the
      outcome of their collisions with the asteroid. We explore how the migration of
      the giant planet would affect the delivery of water and volatile materials to the
      asteroid and we discuss our results in the context of the geophysical and
      collisional evolution of Vesta. In particular, we argue that the observational
      data are best reproduced if the bulk of the impactors was represented by 1-2 km
      wide planetesimals and if Jupiter underwent a limited (a fraction of au)
      displacement. 

PMID- 25370028
TI  - Setting the stage for habitable planets.
AB  - Our understanding of the processes that are relevant to the formation and
      maintenance of habitable planetary systems is advancing at a rapid pace, both
      from observation and theory. The present review focuses on recent research that
      bears on this topic and includes discussions of processes occurring in
      astrophysical, geophysical and climatic contexts, as well as the temporal
      evolution of planetary habitability. Special attention is given to recent
      observations of exoplanets and their host stars and the theories proposed to
      explain the observed trends. Recent theories about the early evolution of the
      Solar System and how they relate to its habitability are also summarized.
      Unresolved issues requiring additional research are pointed out, and a framework
      is provided for estimating the number of habitable planets in the Universe. 

PMID- 25370029
TI  - On the response of halophilic archaea to space conditions.
AB  - Microorganisms are ubiquitous and can be found in almost every habitat and
      ecological niche on Earth. They thrive and survive in a broad spectrum of
      environments and adapt to rapidly changing external conditions. It is of great
      interest to investigate how microbes adapt to different extreme environments and
      with modern human space travel, we added a new extreme environment: outer space.
      Within the last 50 years, technology has provided tools for transporting
      microbial life beyond Earth's protective shield in order to study in situ
      responses to selected conditions of space. This review will focus on halophilic
      archaea, as, due to their ability to survive in extremes, they are often
      considered a model group of organisms to study responses to the harsh conditions
      associated with space. We discuss ground-based simulations, as well as space
      experiments, utilizing archaea, examining responses and/or resistance to the
      effects of microgravity and UV in particular. Several halophilic archaea (e.g.,
      Halorubrum chaoviator) have been exposed to simulated and actual space conditions
      and their survival has been determined as well as the protective effects of
      halite shown. Finally, the intriguing potential of archaea to survive on other
      planets or embedded in a meteorite is postulated. 

PMID- 25370030
TI  - Anaerobic thermophiles.
AB  - The term "extremophile" was introduced to describe any organism capable of living
      and growing under extreme conditions. With the further development of studies on
      microbial ecology and taxonomy, a variety of "extreme" environments have been
      found and an increasing number of extremophiles are being described.
      Extremophiles have also been investigated as far as regarding the search for life
      on other planets and even evaluating the hypothesis that life on Earth originally
      came from space. The first extreme environments to be largely investigated were
      those characterized by elevated temperatures. The naturally "hot environments" on
      Earth range from solar heated surface soils and water with temperatures up to 65 
      degrees C, subterranean sites such as oil reserves and terrestrial geothermal
      with temperatures ranging from slightly above ambient to above 100  degrees C, to
      submarine hydrothermal systems with temperatures exceeding 300  degrees C. There
      are also human-made environments with elevated temperatures such as compost
      piles, slag heaps, industrial processes and water heaters. Thermophilic anaerobic
      microorganisms have been known for a long time, but scientists have often
      resisted the belief that some organisms do not only survive at high temperatures,
      but actually thrive under those hot conditions. They are perhaps one of the most
      interesting varieties of extremophilic organisms. These microorganisms can thrive
      at temperatures over 50  degrees C and, based on their optimal temperature,
      anaerobic thermophiles can be subdivided into three main groups: thermophiles
      with an optimal temperature between 50  degrees C and 64  degrees C and a maximum
      at 70  degrees C, extreme thermophiles with an optimal temperature between 65 
      degrees C and 80  degrees C, and finally hyperthermophiles with an optimal
      temperature above 80  degrees C and a maximum above 90  degrees C. The finding of
      novel extremely thermophilic and hyperthermophilic anaerobic bacteria in recent
      years, and the fact that a large fraction of them belong to the Archaea has
      definitely made this area of investigation more exciting. Particularly
      fascinating are their structural and physiological features allowing them to
      withstand extremely selective environmental conditions. These properties are
      often due to specific biomolecules (DNA, lipids, enzymes, osmolites, etc.) that
      have been studied for years as novel sources for biotechnological applications.
      In some cases (DNA-polymerase, thermostable enzymes), the search and applications
      successful exceeded preliminary expectations, but certainly further exploitations
      are still needed. 

PMID- 25370031
TI  - Neuronal Activity in the Subthalamic Cerebrovasodilator Area under Partial
      Gravity Conditions in Rats.
AB  - The reduced-gravity environment in space is known to cause an upward shift in
      body fluids and thus require cardiovascular adaptations in astronauts. In this
      study, we recorded in rats the neuronal activity in the subthalamic
      cerebrovasodilator area (SVA), a key area that controls cerebral blood flow
      (CBF), in response to partial gravity. "Partial gravity" is the term that defines
      the reduced-gravity levels between 1 g (the unit gravity acceleration on Earth)
      and 0 g (complete weightlessness in space). Neuronal activity was recorded
      telemetrically through chronically implanted microelectrodes in freely moving
      rats. Graded levels of partial gravity from 0.4 g to 0.01 g were generated by
      customized parabolic-flight maneuvers. Electrophysiological signals in each
      partial-gravity phase were compared to those of the preceding 1 g level-flight.
      As a result, SVA neuronal activity was significantly inhibited by the partial
      gravity levels of 0.15 g and lower, but not by 0.2 g and higher. Gravity levels
      between 0.2-0.15 g could represent a critical threshold for the inhibition of
      neurons in the rat SVA. The lunar gravity (0.16 g) might thus trigger neurogenic
      mechanisms of CBF control. This is the first study to examine brain
      electrophysiology with partial gravity as an experimental parameter. 

PMID- 25370032
TI  - Neuromuscular training based on whole body vibration in children with spina
      bifida: a retrospective analysis of a new physiotherapy treatment program.
AB  - INTRODUCTION: Spina bifida is the most common congenital cause of spinal cord
      lesions resulting in paralysis and secondary conditions like osteoporosis due to
      immobilization. Physiotherapy is performed for optimizing muscle function and
      prevention of secondary conditions. Therefore, training of the musculoskeletal
      system is one of the major aims in the rehabilitation of children with spinal
      cord lesions. INTERVENTION AND METHODS: The neuromuscular physiotherapy treatment
      program Auf die Beine combines 6 months of home-based whole body vibration (WBV)
      with interval blocks at the rehabilitation center: 13 days of intensive therapy
      at the beginning and 6 days after 3 months. Measurements are taken at the
      beginning (M0), after 6 months of training (M6), and after a 6-month follow-up
      period (M12). Gait parameters are assessed by ground reaction force and motor
      function by the Gross Motor Function Measurement (GMFM-66). Sixty children (mean
      age 8.71 +/- 4.7 years) who participated in the program until February 2014 were
      retrospectively analyzed. RESULTS: Walking velocity improved significantly by
      0.11 m/s (p = 0.0026) and mobility (GMFM-66) by 2.54 points (p = 0.001) after the
      training. All changes at follow-up were not significant, but significant changes
      were observed after the training period. Decreased contractures were observed
      with increased muscle function. CONCLUSION: Significant improvements in motor
      function were observed after the active training period of the new neuromuscular
      training concept. This first analysis of the new neuromuscular rehabilitation
      concept Auf die Beine showed encouraging results for a safe and efficient
      physiotherapy treatment program which increases motor function in children with
      spina bifida.

PMID- 25370033
TI  - Population pharmacokinetic meta-analysis to bridge ferumoxytol plasma
      pharmacokinetics across populations.
AB  - BACKGROUND: Ferumoxytol is approved for the treatment of iron-deficiency anaemia
      (IDA) in adult patients with chronic kidney disease (CKD). Ferumoxytol has
      recently been investigated for use in all-cause IDA. This analysis was employed
      to bridge ferumoxytol pharmacokinetics (PK) across populations of healthy
      subjects and patients with CKD on haemodialysis, and to then make informed
      inferences regarding the PK behaviour of ferumoxytol in the all-cause IDA
      population. METHODS: The data analysis was performed using NONMEM. Selected
      parameters were included for covariate testing. Investigations to determine if
      changes in volume of distribution during haemodialysis improved the model fit
      were also conducted. The final model was used to simulate PK in healthy
      volunteers (HVs) and CKD patients with and without haemodialysis. RESULTS: The
      final model was a two-compartment model with non-linear elimination. During
      haemodialysis, the central volume V1 was estimated to be reduced by 0.198 L/h. A
      positive relationship was identified between initial V1 and observed weight loss
      during haemodialysis. V1 increased by 0.614 % per kilogram of body weight, and
      females had an 18.3 % lower V1 than males. Differences between simulated profiles
      for different populations were marginal: maximum concentration (Cmax) of 209 vs.
      204 ng/mL and area under the curve from time zero to infinity (AUCinf) of 5,980
      vs. 5,920 ng.h/mL in HVs and CKD non-haemodialysis patients, respectively, for a
      single dose of 510 mg. CONCLUSIONS: The results indicate that ferumoxytol PK are
      comparable between HVs and CKD patients. Furthermore, the results are
      representative of the PK in other populations and can be used to bridge to
      subjects with general IDA.

PMID- 25370034
TI  - Diagnostic approach for FSHD revisited: SMCHD1 mutations cause FSHD2 and act as
      modifiers of disease severity in FSHD1.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular
      disorder with a wide clinical variability. Contractions of the D4Z4
      macrosatellite repeat on chromosome 4q35 are the molecular basis of the
      pathophysiology. Recently, in a subset of patients without D4Z4 repeat
      contractions, variants in the SMCHD1 gene have been identified that lead to
      hypomethylation of D4Z4 and thus DUX4 transcription, which causes FSHD type 2. In
      this study, we have screened 55 FSHD1-negative and 40 FSHD1-positive patients
      from unrelated families for potentially pathogenic variants in SMCHD1 by next
      generation sequencing (NGS). We identified variants in SMCHD1 in 11 index
      patients, including missense, splice site and non-sense mutations. We developed a
      pyrosequencing assay to determine the methylation status of the D4Z4 repeat array
      and found significantly lower methylation levels for FSHD2 patients than for
      healthy controls and FSHD1 patients. Two out of eleven SMCHD1 mutation carriers
      had moderately contracted D4Z4 alleles thus these patients are suffering from
      FSHD1 and 2. Comparing the phenotype of patients, all FSHD2 patients were
      relatively mildly affected while patients with FSHD1+2 were much more severely
      affected than expected from their D4Z4 copy number. Our findings confirm the role
      of SMCHD1 mutations in FSHD2 and as a modifier of disease severity. With SMCHD1
      variants found in 16.4% of phenotypic FSHD patients without D4Z4 repeat
      contractions, the incidence of FSHD2 is rather high and hence we suggest
      including sequencing of SMCHD1, haplotyping and methylation analysis in the
      workflow of molecular FSHD diagnostics. 

PMID- 25370035
TI  - Reply to letter from Felice L. Bedford and Doron Yacobi.

PMID- 25370036
TI  - On two Jewish clades in mitochondrial DNA.

PMID- 25370037
TI  - C6ORF97-ESR1 breast cancer susceptibility locus: influence on progression and
      survival in breast cancer patients.
AB  - Genome-wide association studies have identified a single-nucleotide polymorphism
      (SNP) to be associated with an increased risk of breast cancer. The biology of
      one of the susceptibility locus C6ORF-ESR1 and whether it also contributes to
      progression of established disease has not yet been ascertained. We examined the
      association of rs2046210 and its six linkage disequilibrium SNPs with
      clinicopathological characteristics, prognosis, and gene expression levels of
      ESR1 and the C6ORFs (C6ORF97:CCDC170, C6ORF211, C6ORF96:RMND1) in 344 breast
      cancer tissue samples and 253 corresponding samples of adjacent normal tissue.
      Tumor genotypes with homozygous risk alleles were more frequent than normal
      tissues. The tumor genotypes of rs2046210 and rs6929137 with homozygous risk
      alleles showed worse relapse-free survival (RFS, P=0.038 and P=0.031,
      respectively), whereas no notable associations were observed with either
      clinicopathological characteristics or expression of the peripheral genes. Higher
      C6ORF97 expression correlated with ER negativity (P<0.0001), highly proliferative
      characteristics (P=0.0005 for Ki67, P<0.0001 for nuclear grade) and worse RFS in
      the ER+/HER2- cohort (P=0.013), whereas the other two C6ORFs showed the inverse
      associations. Furthermore, C6ORF97 showed significant worse prognostic values
      especially in luminal B subtype in the publically available data sets. rs2046210
      and the upstream gene C6ORF97 might have substantial roles not only in
      carcinogenesis but also in progression toward a more aggressive phenotype in
      breast cancer patients, which suggests that functional studies of this locus are
      imperative. 

PMID- 25370039
TI  - Meconium ileus in a Lebanese family secondary to mutations in the GUCY2C gene.
AB  - Meconium ileus is most often associated with mutations in the CFTR gene; however
      recently, mutations in GUCY2C in the Bedouin population have also been shown to
      result in this phenotype. This gene codes for an intestinal transmembrane
      receptor that generates cyclic GMP, which activates cystic fibrosis transmembrane
      receptor. We report a third family that supports the association of variants in
      the GUCY2C gene with meconium ileus (MI). A Lebanese kindred was studied and
      individuals affected with MI had either homozygous or compound heterozygous
      variants in GUCY2C. The earliest manifestation of the affected individuals was
      the presence of second trimester fetal echogenic bowel, thus resulting in the
      expansion of the differential diagnosis of this ultrasound finding. 

PMID- 25370038
TI  - Germline variants in POLE are associated with early onset mismatch repair
      deficient colorectal cancer.
AB  - Germline variants affecting the exonuclease domains of POLE and POLD1 predispose
      to multiple colorectal adenomas and/or colorectal cancer (CRC). The aim of this
      study was to estimate the prevalence of previously described heterozygous
      germline variants POLE c.1270C>G, p.(Leu424Val) and POLD1 c.1433G>A,
      p.(Ser478Asn) in a Dutch series of unexplained familial, early onset CRC and
      polyposis index cases. We examined 1188 familial CRC and polyposis index patients
      for POLE p.(Leu424Val) and POLD1 p.(Ser478Asn) variants using competitive allele
      specific PCR. In addition, protein expression of the POLE and DNA mismatch repair
      genes was studied by immunohistochemistry in tumours from POLE carriers. Somatic
      mutations were screened using semiconductor sequencing. We detected three index
      patients (0.25%) with a POLE p.(Leu424Val) variant. In one patient, the variant
      was found to be de-novo. Tumours from three patients from two families were
      microsatellite instable, and immunohistochemistry showed MSH6/MSH2 deficiency
      suggestive of Lynch syndrome. Somatic mutations but no germline MSH6 and MSH2
      variants were subsequently found, and one tumour displayed a hypermutator
      phenotype. None of the 1188 patients carried the POLD1 p.(Ser478Asn) variant.
      POLE germline variant carriers are also associated with a microsatellite instable
      CRC. POLE DNA analysis now seems warranted in microsatellite instable CRC,
      especially in the absence of a causative DNA mismatch repair gene germline
      variant. 

PMID- 25370041
TI  - Genetic testing of children for adult-onset conditions: opinions of the British
      adult population and implications for clinical practice.
AB  - This study set out to explore the attitudes of a representative sample of the
      British public towards genetic testing in children to predict disease in the
      future. We sought opinions about genetic testing for adult-onset conditions for
      which no prevention/treatment is available during childhood, and about genetic
      'carrier' status to assess future reproductive risks. The study also examined
      participants' level of agreement with the reasons professional organisations give
      in favour of deferring such testing. Participants (n=2998) completed a specially
      designed questionnaire, distributed by email. Nearly half of the sample (47%)
      agreed that parents should be able to test their child for adult-onset
      conditions, even if there is no treatment or prevention at time of testing. This
      runs contrary to professional guidance about genetic testing in children. Testing
      for carrier status was supported by a larger proportion (60%). A child's future
      ability to decide for her/himself if and when to be tested was the least
      supported argument in favour of deferring testing. 

PMID- 25370040
TI  - Novel genomic signals of recent selection in an Ethiopian population.
AB  - The recent feasibility of genome-wide studies of adaptation in human populations
      has provided novel insights into biological pathways that have been affected by
      adaptive pressures. However, only a few African populations have been
      investigated using these genome-wide approaches. Here, we performed a genome-wide
      analysis for evidence of recent positive selection in a sample of 120 individuals
      of Wolaita ethnicity belonging to Omotic-speaking people who have inhabited the
      mid- and high-land areas of southern Ethiopia for millennia. Using the 11 HapMap
      populations as the comparison group, we found Wolaita-specific signals of recent
      positive selection in several human leukocyte antigen (HLA) loci. Notably, the
      selected loci overlapped with HLA regions that we previously reported to be
      associated with podoconiosis-a geochemical lymphedema of the lower legs common in
      the Wolaita area. We found selection signals in PPARA, a gene involved in energy
      metabolism during prolonged food deficiency. This finding is consistent with the
      dietary use of enset, a crop with high-carbohydrate and low-fat and -protein
      contents domesticated in Ethiopia subsequent to food deprivation 10 000 years
      ago, and with metabolic adaptation to high-altitude hypoxia. We observed novel
      selection signals in CDKAL1 and NEGR1, well-known diabetes and obesity
      susceptibility genes. Finally, the SLC24A5 gene locus known to be associated with
      skin pigmentation was in the top selection signals in the Wolaita, and the
      alleles of single-nucleotide polymorphisms rs1426654 and rs1834640 (SLC24A5)
      associated with light skin pigmentation in Eurasian populations were of high
      frequency (47.9%) in this Omotic-speaking indigenous Ethiopian population.

PMID- 25370042
TI  - Genotyping of geographically diverse Druze trios reveals substructure and a
      recent bottleneck.
AB  - Druze individuals rarely marry outside their faith (often practicing
      consanguinity) and are thus believed to form a genetic isolate. To
      comprehensively characterize the genetic structure of the Druze population, we
      recruited and genotyped 40 parent-offspring trios from the Upper Galilee in
      Israel and the Golan Heights, attempting to capture different extended families
      (clans) across various geographical locations. Principal component (PC) and
      ADMIXTURE analyses demonstrated that Druze are close to, yet distinct from, other
      Middle-Eastern groups (Bedouins and Palestinians), supporting the Druze's Middle
      Eastern origin and their recent genetic isolation. Reconstruction of the Druze
      demographic history using identical-by-descent (IBD) segments suggested an ~15
      fold reduction in population size taking place ~22-47 generations ago, close to
      the documented time of the foundation of the Druze faith at the 11th century.
      Combining the Galilee and Golan Druze genotypes with previously published data on
      Druze from the Carmel (Israel) and Lebanon demonstrated that all four Druze
      communities are genetically distinct. The Lebanese group shared less IBD segments
      (within the group and with other groups) compared with the Israeli Druze and
      showed higher heterozygosity (suggesting less consanguinity), but was less
      diverse in PC space. These findings suggest complex recent and ancient
      demographic history of the Druze population. 

PMID- 25370043
TI  - p.Arg1809Cys substitution in neurofibromin is associated with a distinctive NF1
      phenotype without neurofibromas.
AB  - Analysis of 786 NF1 mutation-positive subjects with clinical diagnosis of
      neurofibromatosis type 1 (NF1) allowed to identify the heterozygous c.5425C>T
      missense variant (p.Arg1809Cys) in six (0.7%) unrelated probands (three familial
      and three sporadic cases), all exhibiting a mild form of disease. Detailed
      clinical characterization of these subjects and other eight affected relatives
      showed that all individuals had multiple cafe-au-lait spots, frequently
      associated with skinfold freckling, but absence of discrete cutaneous or
      plexiform neurofibromas, Lisch nodules, typical NF1 osseous lesions or
      symptomatic optic gliomas. Facial features in half of the individuals were
      suggestive of Noonan syndrome. Our finding and revision of the literature
      consistently indicate that the c.5425C>T change is associated with a distinctive,
      mild form of NF1, providing new data with direct impact on genetic counseling and
      patient management. 

PMID- 25370045
TI  - [Ebola virus epidemic in West Africa: facts and prospects].

PMID- 25370046
TI  - [The Centre for Medical Research and Health in Niamey, Niger. The new CERMES].
AB  - After 20 years under the umbrella of the Organisation de Coordination et de
      Cooperation pour la lutte contre les Grandes Endemies (organization for
      coordination and cooperation against major endemic diseases), the Centre de
      Recherche sur les Meningites et les Schistosomoses (the meningitis and
      schistosomiasis research center) has been placed under the Niger Ministry of
      Public Health. It has become the Centre de Recherche Medicale et Sanitaire
      (medical and health research center) and thus keeps its acronym, CERMES. In 2008,
      CERMES became a full member of the Institut Pasteur International Network. Its
      main research interests include meningitis, malaria, and interactions between
      health, environment, and climate. CERMES also works in the areas of public health
      and health training. Here, 12 years after the creation of the new CERMES, we
      present its main research results, as well as the challenges and opportunities it
      faces. 

PMID- 25370044
TI  - No evidence for rare recessive and compound heterozygous disruptive variants in
      schizophrenia.
AB  - Recessive inheritance of gene disrupting alleles, either through homozygosity at
      a specific site or compound heterozygosity, have been demonstrated to underlie
      many Mendelian diseases and some complex psychiatric disorders. On the basis of
      exome sequencing data, an increased burden of complete knockout (homozygous or
      compound heterozygous) variants has been identified in autism. In addition, using
      single-nucleotide polymorphism microarray data, an increased rate of homozygosity
      by descent, or autozygosity, has been linked to the risk of schizophrenia (SCZ).
      Here, in a large Swedish case-control SCZ sample (11 244 individuals, 5079 of
      whom have exome sequence data available), we survey the contribution of both
      autozygosity and complete knockouts to disease risk. We do not find evidence for
      association with SCZ, either genome wide or at specific loci. However, we note
      the possible impact of sample size and population genetic factors on the power to
      detect and quantify any burden that may exist. 

PMID- 25370047
TI  - [Heterophile interference: an experimental method of depleting rheumatoid factor
      from sera in Abidjan, Cote d'Ivoire].
AB  - Rheumatoid factor (RF) is a major source of interference in immunoassays. Several
      methods have been proposed to eliminate interference. We experimented with a new
      technique based on the depletion of rheumatoid factor from serum samples. Our
      study included 150 samples, 64 of them positive for RF. Depletion was performed
      by the adsorption of RF from the sample by latex beads sensitized with human IgG
      anti-RF. After precipitation of the complexes formed, the supernatant was tested
      for RF. Finally, we assessed the performance of this RF depletion method with two
      tests: ELISA Enzygnost Enzygnost anti-HBs micro-Behring and IFI falciparum Ref
      75521 Biomerieux. We compared the percentages of false-negative and false
      positive results of these tests before and after depletion of the RF-positive
      serum samples. Efficiency index is 92.2% and the performance of the two
      immunoassay tests improved significantly by a factor of 2 to 25 after depletion.
      In addition, this technique is easy, inexpensive, fast, and suitable to our
      limited resources as a developing country. It should be extended to other
      immunological tests for validation of the results.

PMID- 25370048
TI  - [Ectopic pregnancy at the Ignace Deen University Hospital in Conakry:
      epidemiologic, social, demographic, therapeutic, and prognostic aspects].
AB  - The objectives of this study were to calculate the frequency of ectopic pregnancy
      in the department, define its epidemiological, diagnostic, therapeutic, and
      prognostic aspects, and determine a clear therapeutic approach appropriate to our
      setting. In this prospective study, we compiled all cases of ectopic pregnancy
      seen in 2011 and 2012 in the obstetrics-gynecology department at Ignace Deen
      University Hospital in Conakry. Ectopic pregnancies represented 1.3% of all
      deliveries over this period. In the 111 cases in this population, women aged 30
      34 years accounted for 31.5%, those pregnant for the first time 40.5%,
      nulliparous women 35.1%, married women 72.1%, those without schooling 43.2%), and
      those with a history of sexually transmitted infection 57.6% (these categories
      are not exclusive, and the same women may be included in several). Secondary
      amenorrhea with abdominopelvic pain and metrorrhagia was the reason for admission
      in 56.5% of cases. Ultrasound in early pregnancy is infrequent in Conakry. Almost
      all of our patients underwent emergency surgery (80.2%) More than half of the
      ectopic pregnancies were located in the ampulla of the uterine tubes (73.0%).
      There were three abdominal pregnancies and 2 ovarian. In all cases the treatment
      was surgical, most often salpingectomy. Postoperative complications occurred in
      35.1% of cases, most often anemia (27.9% of all cases) requiring blood
      transfusion in 11.7% of all cases before, during, or after surgery. The maternal
      death rate was 1.8%. Ectopic pregnancy remains a major concern at Ignace Deen
      CHU. Reduction of its frequency requires increased population awareness of
      sexually transmitted infections and illegal abortions. Management should be
      prompt and appropriate. 

PMID- 25370049
TI  - [Skin disease and HIV infection among inmates in Lome, Togo: a study of 194
      prisoners].
AB  - OBJECTIVE: The aim of this work was to study the prevalence of skin diseases
      among inmates in Lome (Togo) and its relation to their HIV status. PATIENTS AND
      METHODS: This cross-sectional descriptive study took place from November 14 to
      December 5, 2011, in the civil prison of Lome and included prisoners who agreed
      to have an HIV screening test. RESULTS: In all, 194 prisoners, all men (median
      age: 29 years), were examined during the study period. The group aged younger
      than 30 years accounted for 51% of the population. Overall, 166 (85.6%) of the
      194 prisoners examined had cutaneous lesions; 153 reported that these had
      developed after their imprisonment. HIV serology was positive in 21 (10.8%) of
      the 194 prisoners tested. The most common cutaneous diseases were pruritus (n =
      62), fungal infections (n = 45), boils (n = 26), eczema (n = 21), and scabies (n
      = 20). The frequency of skin disorders did not differ significantly between HIV
      infected prisoners and those who were not infected (p>0.05). CONCLUSION: This
      study shows a potential for high prevalence of HIV infection and an existing high
      prevalence of infectious dermatosis among these prisoners. It is essential to
      reduce the overpopulation and crowding in prisons to decrease the prevalence of
      these skin disorders.

PMID- 25370051
TI  - The unique serine/threonine phosphatase from the minimal bacterium Mycoplasma
      synoviae: biochemical characterization and metal dependence.
AB  - Serine/threonine protein phosphatases have been described in many pathogenic
      bacteria as essential enzymes involved in phosphorylation-dependent signal
      transduction pathways and frequently associated with the virulence of these
      organisms. An inspection of Mycoplasma synoviae genome revealed the presence of a
      gene (prpC) encoding a putative protein phosphatase of the protein phosphatase 2C
      (PP2C) subfamily. Here, we report a complete biochemical characterization of M.
      synoviae phosphatase (PrpC) and the particular role of metal ions in the
      structure-function relationship of this enzyme. PrpC amino acid sequence analysis
      revealed that all the residues involved in the dinuclear metal center and the
      putative third metal ion-coordinating residues, conserved in PP2C phosphatases,
      are present in PrpC. PrpC is a monomeric protein able to dephosphorylate phospho
      substrates with Mn(2+) ions' dependence. Thermal stability analysis demonstrated
      the enzyme stability at mild temperatures and the influence of Mn(2+) ions in
      this property. Mass spectrometry analysis suggested that three metal ions bind to
      PrpC, two of which with an apparent high-affinity constant. Mutational analysis
      of the putative third metal-coordinating residues, Asp122 and Arg164, revealed
      that these variants exhibited a weaker binding of manganese ions, and that both
      mutations affected PrpC phosphatase activity. According to these results, PrpC is
      a metal-dependent protein phosphatase member with an improved stability in the
      holo form and with Asp122, possibly implicated in the third metal-binding site,
      essential to catalytic activity. 

PMID- 25370052
TI  - PCCM 2014: Extracorporeal support and more.

PMID- 25370050
TI  - Regulation of the NaV1.5 cytoplasmic domain by calmodulin.
AB  - Voltage-gated sodium channels (Na(v)) underlie the rapid upstroke of action
      potentials in excitable tissues. Binding of channel-interactive proteins is
      essential for controlling fast and long-term inactivation. In the structure of
      the complex of the carboxy-terminal portion of Na(v)1.5 (CTNa(v)1.5) with
      calmodulin (CaM)-Mg(2+) reported here, both CaM lobes interact with the
      CTNa(v)1.5. On the basis of the differences between this structure and that of an
      inactivated complex, we propose that the structure reported here represents a non
      inactivated state of the CTNa(v), that is, the state that is poised for
      activation. Electrophysiological characterization of mutants further supports the
      importance of the interactions identified in the structure. Isothermal titration
      calorimetry experiments show that CaM binds to CTNa(v)1.5 with high affinity. The
      results of this study provide unique insights into the physiological activation
      and the pathophysiology of Na(v) channels.

PMID- 25370053
TI  - Sepsis or SEPSIS: does it make a difference?

PMID- 25370054
TI  - How to guide transfusion decision-making? That is the question.

PMID- 25370055
TI  - The tremendous burden of sepsis on China's youngest children.

PMID- 25370056
TI  - Are we exchanging morbidity for mortality in pediatric intensive care?

PMID- 25370057
TI  - Sepsis in children: a dark cloud with a silver lining.

PMID- 25370058
TI  - Treatment of a mostly self-limiting disease: keep it simple and safe.

PMID- 25370059
TI  - Connecting the dots: from time point to trajectory analysis of serum sodium
      levels in pediatric neurologic injury.

PMID- 25370060
TI  - Enhancing the power of simulation for complex clinical care.

PMID- 25370061
TI  - Extubation and extracorporeal membrane oxygenation: what a difference a decade
      makes!!

PMID- 25370062
TI  - Is this heart going to work?

PMID- 25370063
TI  - Pediatric perioperative outcomes in the developing world: where are we now?

PMID- 25370064
TI  - Diastolic dysfunction in children with septic shock: does it help us manage our
      patients?

PMID- 25370065
TI  - Liquid ventilation in congenital diaphragmatic hernia: back on stage?

PMID- 25370066
TI  - What are the new perspectives in rehabilitation in the PICU using traditional
      techniques?

PMID- 25370067
TI  - The author replies.

PMID- 25370068
TI  - What is the meaning of hypertension in the PICU?

PMID- 25370069
TI  - The authors reply.

PMID- 25370070
TI  - Intrapulmonary instillation of perflurooctylbromide improves lung growth,
      alveolarization, and lung mechanics in a fetal rabbit model of diaphragmatic
      hernia.
AB  - OBJECTIVES: Fetal tracheal occlusion of hypoplastic rabbit lungs results in lung
      growth and alveolarization although the surfactant protein messenger RNA
      expression is decreased and the transforming growth factor-beta pathway induced.
      The prenatal filling of healthy rabbit lungs with perfluorooctylbromide augments
      lung growth without suppression of surfactant protein synthesis. We hypothesizes
      that Intratracheal perfluorooctylbromide instillation improves lung growth,
      mechanics, and extracellular matrix synthesis in a fetal rabbit model of lung
      hypoplasia induced by diaphragmatic hernia. SETTING AND INTERVENTIONS: On day 23
      of gestation, DH was induced by fetal surgery in healthy rabbit fetuses. Five
      days later, 0.8ml of perfluorooctylbromide (diaphragmatic hernia
      perfluorooctylbromide) or saline (diaphragmatic hernia-saline) was randomly
      administered into the lungs of previously operated fetuses. After term delivery
      (day 31), lung mechanics, lung to body weight ratio, messenger RNA levels of
      target genes, assessment of lung histology, and morphological distribution of
      elastin and collagen were determined. Nonoperated fetuses served as controls.
      MEASUREMENTS AND MAIN RESULTS: Fetal instillation of perfluorooctylbromide in
      hypoplastic lungs resulted in an improvement of lung-to-body weight ratio (0.016
      vs 0.013 g/g; p = 0.05), total lung capacity (23.4 vs 15.4 MUL/g; p = 0.03), and
      compliance (2.4 vs 1.2 mL/cm H2O; p = 0.007) as compared to diaphragmatic hernia
      saline. In accordance with the results from lung function analysis, elastin
      staining of pulmonary tissue revealed a physiological distribution of elastic
      fiber to the tips of the secondary crests in the diaphragmatic hernia
      perfluorooctylbromide group. Likewise, messenger RNA expression was induced in
      genes associated with extracellular matrix remodeling (matrix metalloproteinase
      2, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of
      metalloproteinase-2). Surfactant protein expression was similar in the
      diaphragmatic hernia-perfluorooctylbromide and diaphragmatic hernia-saline
      groups. Distal airway size, mean linear intercept, as well as airspace and tissue
      fractions were similar in diaphragmatic hernia-perfluorooctylbromide,
      diaphragmatic hernia-saline, and control groups. CONCLUSIONS: Fetal
      perfluorooctylbromide treatment improves lung growth, lung mechanics, and
      extracellular matrix remodeling in hypoplastic lungs, most probably due to
      transient pulmonary stretch, preserved fetal breathing movements, and its
      physical characteristics. Perfluorooctylbromide instillation is a promising
      approach for prenatal therapy of lung hypoplasia.

PMID- 25370071
TI  - Increase in oxygen consumption after albuterol inhalation in ventilated infants
      and children.
AB  - OBJECTIVE: To determine if inhaled albuterol (salbutamol) increases oxygen
      consumption (V'O2) in children and, if so, the duration of this effect. DESIGN:
      Oxygen consumption was measured by indirect calorimetry using the Argon dilution
      technique with a respiratory mass spectrometer. After measurement of baseline
      values, albuterol was administered and subsequent measurements were performed at
      10 minutes, 1 hour, 2 hours, 3 hours, and 4 hours. SETTING: Multidisciplinary
      PICU in a university teaching hospital. PATIENTS: Eleven intubated infants and
      children (five girls, six boys) with a mean age of 20 months (range, 1 mo to 8
      yr) and a mean weight of 10.7 kg (range, 3.1-23 kg) who required therapeutic
      albuterol inhalations. INTERVENTION: Nine hundred micrograms of albuterol (10
      puffs) was administered by a metered-dose inhaler into a spacer through the
      inspiratory arm of the ventilator circuit near to the patient, during 10
      mechanically assisted breaths. MEASUREMENTS AND MAIN RESULTS: All children showed
      an increase in V'O2 within 10 minutes (mean increase 48.6%). The increased V'O2
      was still elevated (42.3% above baseline) at 1 hour, but 3 hours after albuterol
      inhalation, the V'O2 was back to baseline in all patients. Heart rate increased
      significantly at 10 minutes, 1 hour, and 2 hours after inhalation. CONCLUSION:
      There is a large increase in V'O2 after albuterol inhalation. This effect lasts
      up to 3 hours.

PMID- 25370072
TI  - Quantum magnetic phase transition in square-octagon lattice.
AB  - Quantum magnetic phase transition in square-octagon lattice was investigated by
      cellular dynamical mean field theory combining with continuous time quantum Monte
      Carlo algorithm. Based on the systematic calculation on the density of states,
      the double occupancy and the Fermi surface evolution of square-octagon lattice,
      we presented the phase diagrams of this splendid many particle system. The
      competition between the temperature and the on-site repulsive interaction in the
      isotropic square-octagon lattice has shown that both antiferromagnetic and
      paramagnetic order can be found not only in the metal phase, but also in the
      insulating phase. Antiferromagnetic metal phase disappeared in the phase diagram
      that consists of the anisotropic parameter lambda and the on-site repulsive
      interaction U while the other phases still can be detected at T = 0.17. The
      results found in this work may contribute to understand well the properties of
      some consuming systems that have square-octagon structure, quasi square-octagon
      structure, such as ZnO. 

PMID- 25370073
TI  - Rapid screening of peptide probes through in situ single-bead sequencing
      microarray.
AB  - Peptide ligands as targeting probes for in vivo imaging and drug delivery have
      attracted great interest in the biomedical community. However, high affinity and
      specificity screening of large peptide libraries remains a tedious process. Here,
      we report a continuous-flow microfluidic method for one-bead-one-compound (OBOC)
      combinatorial peptide library screening. We screened a library with 2 * 10(5)
      peptide beads within 4 h and discovered 140 noncanonical peptide hits targeting
      the tumor marker, aminopeptidase N (APN). Using the Clustal algorithm, we
      identified the conserved sequence Tyr-XX-Tyr in the N terminal. We demonstrated
      that the novel sequence YVEYHLC peptides have both nanomolar affinity and high
      specificity for APN in ex vivo and in vivo models. We envision that the
      successful demonstration of this integrated novel nanotechnology for peptide
      screening and identification open a new avenue for rapid discovery of new peptide
      based reagents for disease diagnostics and therapeutics. 

PMID- 25370074
TI  - Screening of human chromosome 21 genes in the dorsolateral prefrontal cortex of
      individuals with Down syndrome.
AB  - The aim of the current study was to identify the genes on human chromosome 21
      (HC21) that may serve important functions in the pathogenesis of Down syndrome
      (DS). The microarray data GSE5390 were obtained from the Gene Expression Omnibus
      database, which contained 7 DS and 8 healthy normal samples. The data were then
      normalized and the differentially expressed genes (DEGs) were identified using
      the LIMMA package and Bonferroni correction. Furthermore, the DEGs underwent
      clustering and gene ontology analysis. Additionally, the locations of the DEGs on
      HC21 were confirmed using human genome 19 in the University of California, Santa
      Cruz Interaction Browser. A total of 25 upregulated and 275 downregulated genes
      were screened between DS and healthy samples with a false discovery rate of <0.05
      and |logFC|>1. The expression levels of these genes in the two samples were
      different. In addition, the up- and downregulated genes were markedly enriched in
      organic substance biological processes (P=4.48x10-10) and cell-cell signaling
      (P=0.000227). Furthermore, 17 overexpressed genes were identified on the 21q21-22
      area, including COL6A2, TTC3 and ABCG1. Together, these observations suggest that
      17 upregulated genes on HC21 may be involved in the development of DS and provide
      the basis for understanding this disability.

PMID- 25370076
TI  - The voices of Iris: Cinematic representations of the aged woman and Alzheimer's
      disease in Iris (2001).
AB  - Audiences must be critical of film representations of the aged woman living with
      Alzheimer's disease and of dangerous reinscriptions of stereotypical equations
      about ageing as deterioration. This paper analyses the representation and decline
      of the aged woman through the different voices of Iris Murdoch in Richard Eyre's
      film Iris (2001). Key vocal scenes are considered: On-screen encounters between
      young and aged Iris, vocal representations of dementia symptoms and silencing
      Iris as her disease progresses. Further, Iris' recurrent unaccompanied song, "The
      Lark in the Clear Air," compels audiences to "see" Iris with their ears more than
      with their eyes, exemplifying the representational power of sound in film. This
      paper is an appeal for increased debate about sonic representations of aged
      women, ageing and Alzheimer's disease and dementia in film. The significance of
      audiences' critical awareness and understanding about the social implications of
      these representations is discussed. 

PMID- 25370075
TI  - Shared decision-making in dementia: A review of patient and family carer
      involvement.
AB  - This paper reviews empirical findings concerning the decision-making process of
      persons with dementia and their family carers, with a particular focus on the
      extent and determinants of involvement of persons with dementia in the decision
      making process. To be included in this review, studies needed to be published in
      peer-reviewed journals between 1999 and 2014, report empirical data from
      participants with dementia and/or their family carers, and pertain to the
      involvement of persons with dementia and their family carers in decisions about
      everyday care, medical care and treatment, or long-term care. A total of 36
      studies were included. Results indicated that not all persons with dementia are
      excluded from participating in the decision-making process, but there is a broad
      spectrum of what constitutes shared decision-making in dementia. Studies
      concerning the determinants of shared decision-making mostly focused on non
      modifiable factors. Future research is needed to better promote shared decision
      making among persons with dementia and their family carers. 

PMID- 25370077
TI  - Person-centred dementia care: a reality check in two nursing homes in Ireland.
AB  - The introduction of a person-centred care (PCC) approach to dementia care has
      been a major paradigmatic shift in the care provision in residential settings for
      older adults in Ireland. However, policy implementation in nursing homes relies
      very much on the preparedness of nursing staff. This study explored this through
      semi-structured interviews with care assistants in two nursing homes which
      professed to support the PCC philosophy. We addressed their knowledge and
      perspectives of person-centred dementia care and views on various factors
      affecting its delivery. Findings showed considerable disparity between policy and
      practice, in particular because care assistants lacked clarity on what PCC is and
      reported that they were not educated in it. Notwithstanding this, carers'
      perspectives on 'good care' for people with dementia included elements of PCC
      which suggested its 'implicit' use in practice. Besides the necessity of more
      (and more explicit) training on PCC, the findings also suggest concerns around
      communication between staff and management and the need for improvement of
      staffing resources and available time in residential settings in order to make
      the delivery of person-centred dementia care a reality. 

PMID- 25370078
TI  - Novel pyrano and vinylphenol adducts of deoxyanthocyanidins in sorghum sourdough.
AB  - This study determined the fate of deoxyanthocyanidins in sorghum sourdoughs.
      Sourdoughs prepared from the red sorghum variety Town were fermented with the
      caffeic acid-decarboxylating strains Lactobacillus plantarum FUA3171 and the
      decarboxylase negative L. casei FUA3166. Deoxyanthocyanidins were analyzed by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). Apigeninidin and
      methoxyapigeninidin were the major deoxyanthocyanidins prior to fermentation.
      During fermentation, novel deoxyanthocyanidins were formed. Purification by
      preparative LC, followed by NMR analysis and high-resolution MS identified two of
      the compounds as 6-deoxyanthocyanidin-vinylphenol and pyrano-3
      deoxyanthocyanidin. To identify pathways for their formation, sorghum was
      fermented with single strains, L. plantarum or L. casei. 6-Deoxyanthocyanidin
      vinylphenol and pyrano-3-deoxyanthocyanidin were formed only during fermentation
      with L. plantarum FUA3171, indicating a role of vinylphenol in their formation.
      Chemical synthesis confirmed that 6-deoxyanthocyanidin-vinylphenol and pyrano-3
      deoxyanthocyanidin are formed from apigeninidin with vinylphenol but not with p
      coumaric acid as reactants. In conclusion, the products of microbial
      decarboxylation of hydroxycinnamic acids convert apigeninidin and
      methoxyapigeninidin to pyrano-3-deoxyanthocyanidins and vinylphenol adducts. 

PMID- 25370079
TI  - Identification of novel epigenetically inactivated gene PAMR1 in breast
      carcinoma.
AB  - Development of cancer is a complex process involving multiple genetic and
      epigenetic alterations. In our microarray analysis of 81 breast carcinoma
      specimens, we identified peptidase domain containing associated with muscle
      regeneration 1 (PAMR1) as being frequently suppressed in breast cancer tissues.
      PAMR1 expression was also reduced in all tested breast cancer cell lines, while
      PAMR1 was expressed moderately in normal breast tissues and primary mammary
      epithelial cells. DNA sequencing of the PAMR1 promoter after sodium bisulfite
      treatment revealed that CpG sites were hypermethylated in the breast cancer
      tissues and cell lines. PAMR1 expression was restored by 5-aza-2' deoxycytidine
      treatment, demonstrating that promoter hypermethylation contributed to PAMR1
      inactivation in the breast cancer cells. In addition, ectopic expression of PAMR1
      markedly suppressed cancer cell growth. In summary, our study identified PAMR1 as
      a putative tumor suppressor which was frequently inactivated by promoter
      hypermethylation in breast cancer tissues.

PMID- 25370080
TI  - A meta-analysis of the effectiveness of crew resource management training in
      acute care domains.
AB  - The healthcare industry has seen an increase in the adoption of team training,
      such as crew resource management (CRM), to improve teamwork and coordination
      within acute care medical teams. A meta-analysis was carried out in order to
      quantify the effects of CRM training on reactions, learning, behaviour and
      clinical care outcomes. Biases in the research evidence are identified and
      recommendations for training development and evaluation are presented. PUBMED,
      EMBASE and PsychInfo were systematically searched for all relevant papers. Peer
      reviewed papers published in English between January 1985 and September 2013,
      which present empirically based studies focusing on interventions to improve team
      effectiveness in acute health care domains, were included. A total of 20 CRM-type
      team training evaluation studies were found to fulfil the a priori criteria for
      inclusion in the meta-analysis. Overall, CRM trained participants responded
      positively to CRM (mean score 4.25 out of a maximum of 5), the training had large
      effects on participants' knowledge (d=1.05), a small effect on attitudes (d=0.22)
      and a large effect on behaviours (d=1.25). There was insufficient evidence to
      support an effect on clinical care outcomes or long term impacts. The findings
      support the premise that CRM training can positively impact teamwork in
      healthcare and provide estimates of the expected effects of training. However,
      there is a need for greater precision in outcome assessment, improved
      standardisation of methods and measures, and more robust research design.
      Stronger evidence of effectiveness will require multi-level, multicentre,
      multispecialty and longitudinal studies.

PMID- 25370081
TI  - Associations between primary open angle glaucoma, Alzheimer's disease and
      vascular dementia: record linkage study.
AB  - AIMS: The potential association between primary open angle glaucoma (POAG) and
      Alzheimer's disease (AD) is uncertain and has implications for understanding
      disease pathogenesis, referral and treatments. The aim was to determine whether
      individuals diagnosed with POAG are at higher risk of subsequently developing AD
      or vascular dementia. METHODS: A POAG cohort of 87 658 people was constructed
      from English National Health Service linked hospital episode statistics from 1999
      to 2011. An AD cohort (251 703 people), vascular dementia cohort (217 302 people)
      and reference cohort (>2.5 million people) were constructed in similar ways. Risk
      of dementia following POAG was determined: rate ratios were calculated based on
      standardised rates of dementia in the POAG cohort. RESULTS: The risk of AD
      following a diagnosis of POAG was not elevated: the rate ratio was 1.01 (95% CI
      0.96 to 1.06). The risk of vascular dementia after POAG was modestly elevated,
      with rate ratio 1.10 (1.05 to 1.16). The likelihood of a hospital record of POAG
      following AD or vascular dementia was very low, with rate ratios 0.28 (0.24 to
      0.31) and 0.32 (0.28 to 0.37), respectively. CONCLUSIONS: POAG and AD are
      neurodegenerative conditions that share some pathological features. However,
      considering AD after POAG, their coexistence at the individual level is no
      different from that expected by chance. By contrast, a diagnosis of POAG is
      modestly associated with later development of vascular dementia, presumably owing
      to shared vascular risk factors. People with dementia in England are much less
      likely to be admitted subsequently with POAG, perhaps through poor access to
      hospital eye services and diagnostic challenges.

PMID- 25370082
TI  - Peripheral refraction in 7- and 14-year-old children in central China: the Anyang
      Childhood Eye Study.
AB  - PURPOSE: To determine the distribution of peripheral refraction, including
      astigmatism, in 7- and 14-year-old Chinese children. METHODS: 2134 7-year-old and
      1780 14-year-old children were measured with cycloplegic central and horizontal
      peripheral refraction (15 degrees  and 30 degrees  at temporal and nasal visual
      fields). RESULTS: 7- and 14-year-old children included 9 and 594, respectively,
      with moderate and high myopia (<=-3.0 D), 259 and 831 with low myopia (-2.99 to 
      0.5 D), 1207 and 305 with emmetropia (-0.49 to +1.0 D), and 659 and 50 with
      hyperopia (>1.0 D), respectively. Myopic children had relative peripheral
      hyperopia while hyperopic and emmetropic children had relative peripheral myopia,
      with greater changes in relative peripheral refraction occurring in the nasal
      than the temporal visual field. The older group had the greater relative
      peripheral hyperopia and higher peripheral J180. Both age groups showed positive
      slopes of J45 across the visual field, with greater slopes in the older group.
      CONCLUSIONS: Myopic children in mainland China have relative peripheral hyperopia
      while hyperopic and emmetropic children have relative peripheral myopia.
      Significant differences exist between 7- and 14-year-old children, with the
      latter showing more relative peripheral hyperopia, greater rate of change in J45
      across the visual field, and higher peripheral J180.

PMID- 25370083
TI  - Long-term efficacy and complications of black diaphragm intraocular lens
      implantation in patients with traumatic aniridia.
AB  - AIMS: To determine the efficacy and complications of long-term black diaphragm
      intraocular (BDI) lens implantation in patients with traumatic aniridia. METHODS:
      This study analysed the demographics, clinical evaluations and treatments of 95
      patients with BDI lens implantation and 75 patients who wore rigid gas-permeable
      (RGP) contact lenses (CLs). The clinical examinations included evaluations of
      visual acuity (VA), best-corrected visual acuity (BCVA), intraocular pressure
      measurements (IOP), and corneal endothelial cell density (ECD). Ultrasound
      biomicroscopy (UBM) was used to observe the haptic lens positions. RESULTS: In
      the BDI group, light sensitivity dramatically decreased postoperatively in all
      patients, and 78 patients (82.1%) had a BCVA score >20/200. A total of 36 eyes
      (37.89%) developed elevated IOP after the BDI lens implantation, and 12 eyes
      (12.63%) underwent glaucoma laser surgery. Corneal decompensation occurred in
      nine eyes (9.47%), three of which developed glaucoma. Twelve patients (12.63%)
      experienced limbal stem cell failure, and 16 patients (16.84%) had eccentric BDI
      lenses. All patients in the RGP group had a BCVA score >=20/200. Only seven eyes
      (9.3%) had cornea complications. There were no statistically significant
      differences in either the IOP or ECD after wearing the RGP CLs. CONCLUSIONS:
      Glaucoma, corneal decompensation, limbal stem cell failure, and eccentric BDI
      lenses appeared to be the major long-term complications in BDI lens implantation.
      BDI lens implantation could effectively improve postoperative outcomes by
      reducing glare disability, improving visual performance, and addressing cosmetic
      issues. Because the implantation of the BDI lens in traumatic aniridia had a high
      incidence of complications, this treatment should be used with caution, and the
      long-term complications should be seriously considered.

PMID- 25370084
TI  - Comparison of umbilical cord serum and amniotic membrane transplantation in acute
      ocular chemical burns.
AB  - PURPOSE: To compare the efficacy of umbilical cord serum (UCS) with amniotic
      membrane transplantation (AMT) in cases of acute ocular chemical burns. METHODS:
      In a retrospective, interventional, comparative case series, 55 eyes with grades
      III, IV and V chemical burns (Dua's classification) who presented within 3 weeks
      of injury were evaluated. Patients were treated with conventional medical (CM
      group, 20 eyes) management alone or combined with either UCS (UCS group, 17 eyes)
      or AMT (AMT group, 18 eyes). The parameters evaluated were time to
      epithelialisation, epithelial defect diameter, epithelial defect area, corneal
      clarity, tear break-up time (TBUT), Schirmer test and best-corrected vision.
      RESULTS: UCS and AMT groups showed early epithelialisation as compared with the
      CM group (Kaplan-Meier analysis=0.01). Mean time for healing of epithelial defect
      was 57.7+/-29.3, 27.4+/-19.0, 41.1+/-28.9 days in the CM, UCS and AMT groups,
      respectively (p=0.02). Mean TBUT at the last follow-up was 8.6+/-0.7, 10.3+/-1.1,
      9.4+/-1.2 s in the CM, UCS and AMT groups, respectively (p=0.02). The mean
      Schirmer value at the last follow-up was 13.7+/-1.0, 16.9+/-3.0 and 13.2+/-1.5 mm
      in the CM, UCS and AMT groups, respectively (p=0.01). The visual outcomes and the
      occurrence of corneal vascularisation, symblepheron, ectropion and entropion were
      comparable in between the groups. CONCLUSIONS: Our study suggests that the UCS
      therapy may be a better alternative to AMT in acute moderate to severe (grades
      III, IV and V) ocular chemical burns, as it avoids surgical manoeuvre in already
      inflamed eyes.

PMID- 25370085
TI  - Towards best practice in national health workforce planning.
AB  - Health Workforce Australia (HWA) was established by the Council of Australian
      Governments through its 2008 National Partnership Agreement on Hospital and
      Health Workforce Reform, as the national agency to progress health workforce
      reform and address the challenges of providing a skilled, innovative and flexible
      health workforce in Australia. The Australian Health Ministers' Conference
      commissioned HWA to undertake a workforce planning exercise for doctors, nurses
      and midwives over a planning horizon to 2025. Health Workforce 2025 (HW 2025) was
      conducted in two phases: developing projections for the size and type of the
      health workforce (doctors, nurses and midwives) needed to meet future service
      requirements from 2012 to 2025; and modelling the training pipeline necessary to
      meet the size and type of this health workforce. HWA has used a number of key
      principles in developing HW 2025 to ensure the projections are robust and able to
      be applied nationally. HW 2025 is not a one-off project. Projections will be
      updated as new data become available, and methodology and assumptions
      underpinning the projections will be periodically reviewed. To also ensure the
      continued improvement of national health workforce planning, HWA is pursuing
      other areas for improvement, including better national data collections and
      improved estimation methodology for demand. Results of HW 2025 were presented to
      the Australian Health Ministers (through the Standing Council on Health) in April
      2012.

PMID- 25370086
TI  - Sustainable workforce and sustainable health systems for rural and remote
      Australia.
AB  - Adequate health workforce alone will not ensure optimal health service access. We
      consider what an effective and sustainable health system for rural and remote
      Australia might look like in 2025, briefly describe some of the barriers to
      achieving this vision and propose how these challenges may be overcome. More
      radical change is required on at least four fronts: changing the prevailing ethos
      about rural and remote health; addressing persistent gaps in workforce education
      and training; delivery of comprehensive service models; and accountability. 

PMID- 25370087
TI  - International medical migration: what is the future for Australia?

PMID- 25370088
TI  - A framework to support team-based models of primary care within the Australian
      health care system.
AB  - Health systems with strong primary care orientations are known to be associated
      with improved equity, better access for patients to appropriate services at lower
      costs, and improved population health. Team-based models of primary care have
      emerged in response to health system challenges due to complex patient profiles,
      patient expectations and health system demands. Successful team-based models of
      primary care require a combination of interprofessional education and learning;
      organisational and management policies and systems; and practice support systems.
      To ensure evidence is put into practice, we propose a framework comprising five
      domains (theory, implementation, infrastructure, sustainability and evaluation)
      to assist policymakers, educators, researchers, managers and health professionals
      in supporting team-based models of primary care within the Australian health care
      system. 

PMID- 25370089
TI  - The future of Australian medical education: a focus on technology.

PMID- 25370090
TI  - Paying for the health workforce.

PMID- 25370091
TI  - The medical workforce of the future.

PMID- 25370092
TI  - Towards a sustainable and fit-for-purpose health workforce--lessons from New
      Zealand.

PMID- 25370093
TI  - The medical workforce in 2025: what's in the numbers?
AB  - Key trends in Australian medical workforce supply include increasing overall
      supply levels and an increasing number of medical graduates, but also reduced
      workforce effort and a large cohort of doctors approaching traditional retirement
      age. Although prevocational and vocational training programs are beginning to
      expand, there are significant bottlenecks in the postgraduate training pathway
      for the sizeable cohorts of new graduates. The primary health care workforce
      needs continued development, including team-based approaches to care and
      increased use of technology. Increasing our understanding of system-level and
      individual-level determinants of doctors' choices and implementing innovative
      strategies to accommodate the increasingly diverse work patterns of doctors are
      critical to ensuring that in future there are sufficient doctors, with the right
      skills, in the right places. 

PMID- 25370094
TI  - Enantiomers of a selective gelatinase inhibitor: (R)- and (S)-2-[(4
      phenoxyphenyl)sulfonylmethyl]thiirane.
AB  - The compound 2-[(4-phenoxyphenyl)sulfonylmethyl]thiirane, C15H14O3S2, a selective
      gelatinase inhibitor, was synthesized and structurally characterized. Two
      crystals were analyzed, one each for the R and S enantiomers, and the results
      were compared with the previously reported structure of the racemate. The
      enantiomerically pure compounds both crystallize with Z' = 2 in the space group
      P21, while the racemic mixture crystallizes with Z' = 1 in the space group P21/c,
      with disorder in the position of the thiirane group. This disorder accommodates
      both molecules for each of the enantiomerically pure crystals, showing good
      overlap of the molecules of the pure enantiomorphs with the components of the
      centrosymmetric structure.

PMID- 25370095
TI  - Dendocarbin A: a sesquiterpene lactone from Drimys winteri.
AB  - The natural compound dendocarbin A, C15H22O3, is a sesquiterpene lactone isolated
      for the first time from Drimys winteri for var chilensis. The compound
      crystallizes in the orthorhombic space group P212121 and its X-ray crystal
      structure confirmed the S/R character of the chiral centres at C-5/C-10 and C-9/C
      11, respectively. The alpha-OH group at C-11 was found to be involved in
      intermolecular hydrogen bonding, defining chains along the <100> 21 screw axis.

PMID- 25370096
TI  - (2E)-3-(6-methoxynaphthalen-2-yl)-1-(pyridin-3-yl)prop-2-en-1-one and its
      cyclocondensation product with guanidine, (4RS)-2-amino-4-(6-methoxynaphthalen-2
      yl)-6-(pyridin-3-yl)-3,4-dihydropyrimidine monohydrate: two types of hydrogen
      bonded sheet.
AB  - The structures of a chalcone and of its cyclocondensation product with guanidine
      are reported. In (2E)-3-(6-methoxynaphthalen-2-yl)-1-(pyridin-3-yl)prop-2-en-1
      one, C19H15NO2, (I), the planes of the pyridine and naphthalene units make
      dihedral angles with that of the central spacer unit of 23.61 (13) and 23.57 (15)
      degrees , respectively, and a dihedral angle of 47.24 (9) degrees  with each
      other. The molecules of (I) are linked into sheets by a combination of C-H...O
      and C-H...pi(arene) hydrogen bonds. In the cyclocondensation product (4RS)-2
      amino-4-(6-methoxynaphthalen-2-yl)-6-(pyridin-3-yl)-3,4-dihydropyrimidine
      monohydrate, C20H18N4O.H2O, (II), the dihydropyrimidine ring adopts a
      conformation best described as a shallow boat. The molecular components are
      linked by two N-H...O hydrogen bonds, two O-H...N hydrogen bonds and one N-H...N
      hydrogen bond to form complex sheets, with the methoxynaphthalene interdigitated
      between inversion-related pairs of sheets.

PMID- 25370097
TI  - Poly[(MU-pentafluorobenzoato-kappa2O:O')(pentafluorobenzoato-kappaO)(MU-pyrazine
      kappa2N:N')copper(II)]: a coordination polymer linked into a three-dimensional
      network by intermolecular C-H...F-C interactions.
AB  - In the title compound, [Cu(C6F5COO)2(C4H4N2)]n, (I), the asymmetric unit contains
      one Cu(II) cation, two anionic pentafluorobenzoate ligands and one pyrazine
      ligand. Each Cu(II) centre is five-coordinated by three O atoms from three
      independent pentafluorobenzoate anions, as well as by two N atoms from two
      pyrazine ligands, giving rise to an approximately square-pyramidal coordination
      geometry. Adjacent Cu(II) cations are bridged by a pyrazine ligand and two
      pentafluorobenzoate anions to give a two-dimensional layer. The layers are
      stacked to generate a three-dimensional supramolecular architecture via strong
      intermolecular C-H...F-C interactions, as indicated by the F...H distance of 2.38
      A.

PMID- 25370098
TI  - Ionothermal synthesis and crystal structure of a new organic-inorganic hybrid
      compound: catena-poly[bis(1-ethyl-3-methylimidazolium) [hepta-MU-bromido
      pentacuprate(I)]].
AB  - A new organic-inorganic hybrid compound, catena-poly[bis(1-ethyl-3
      methylimidazolium) [MU5-bromido-tri-MU3-bromido-tri-MU2-bromido
      pentacuprate(I)]], {(C6H11N2)2[Cu5Br7]}n, has been obtained under ionothermal
      conditions from a reaction mixture containing Ba(OH)2.8H2O, Cu(OH)2.2H2O, As2O5,
      1-ethyl-3-methylimidazolium bromide and distilled water. The crystal structure
      consists of complex [Cu5Br7](2-) anions arranged in sinusoidal {[Cu5Br7](2-)}n
      chains running along the a axis, which are surrounded by 1-ethyl-3
      methylimidazolium cations. Three of the five unique Br atoms and one of the three
      Cu(I) atoms occupy special positions with half-occupancy (a mirror plane
      perpendicular to the b axis, site symmetry m). The Cu(I) ions are in a distorted
      tetrahedral coordination environment, with four Br atoms at distances ranging
      from 2.3667 (10) to 2.6197 (13) A, and an outlier at 3.0283 (12) A, exceptionally
      elongated and with a small contribution to the bond-valence sum of only 6.7%.
      Short C-H...Br contacts build up a three-dimensional network. The Cu...Cu
      distances within the chain range from 2.8390 (12) to 3.0805 (17) A, indicating
      the existence of weak Cu(I)...Cu(I) cuprophilic interactions.

PMID- 25370099
TI  - A three-dimensional Cd(II) coordination framework: poly[di-MU2-aqua-{MU2-1,4
      bis[(1H-1,2,4-triazol-1-yl)methyl]benzene-kappa2N4:N4'}di-MU3-terephthalato
      kappa3O:O':O''-dicadmium(II)].
AB  - The title Cd(II) coordination polymer, [Cd(C10H8O4)(C12H12N6)(0.5)(H2O)]n, has
      been obtained by the hydrothermal method and studied by single-crystal X-ray
      diffraction, elemental analysis, thermogravimetric analysis, IR spectroscopy and
      fluorescence spectroscopy. The compound forms a novel three-dimensional framework
      with 3,8-connected three-dimensional binodal {4.5(2)}2{4(2).5(10).6(12).7.8(3)}
      topology. An investigation of its photoluminescence properties shows that the
      compound exhibits a strong fluorescence emission in the solid state at room
      temperature.

PMID- 25370100
TI  - A three-dimensional cyanide-bridged heterometallic coordination polymer:
      poly[[diacetonitrilediaqua[MU2-3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine
      kappa4N1,N6:N3,N4]tetra-MU-cyanido-tetracyanidodimanganese(II)molybdate(IV)]
      dihydrate].
AB  - A metal coordination polymer, {[Mn2Mo(CN)8(C12H8N6)(CH3CN)2(H2O)2].2H2O}n, has
      been synthesized by the reaction of Mn(ClO4)2.6H2O with 3,6-bis(pyridin-2-yl)
      1,2,4,5-tetrazine (bptz) and (Bu3N)3[Mo(CN)8] at room temperature. The polymer
      was characterized by IR spectroscopy, elemental analysis and X-ray diffraction,
      and the magnetic properties were also investigated. The X-ray diffraction
      analysis reveals that the compound is a new three-dimensional coordination
      polymer with a PtS-type network. Magnetic investigation shows antiferromagnetic
      coupling between adjacent Mn(2+) cations. 

PMID- 25370101
TI  - A one-dimensional Zn(II) coordination polymer: poly[dichlorido(MU2-1,4
      phenylenediacetato-kappa2O:O')bis{MU2-1,3-bis[(1H-1,2,4-triazol-1
      yl)methyl]benzene-kappa2N3:N3'}dizinc(II)].
AB  - In the title one-dimensional Zn(II) coordination polymer,
      [Zn(C10H8O4)(0.5)Cl(C12H12N6)]n, the asymmetric unit consists of a Zn(II) cation,
      a 1,3-bis[(1H-1,2,4-triazol-1-yl)methyl]benzene ligand and half of a fully
      deprotonated centrosymmetric 1,4-phenylenediacetic acid ligand. The crystal
      structure shows a one-dimensional rotaxane-like structure. This coordination
      polymer is reinforced by C-H...O and C-H...Cl hydrogen bonds and pi-pi
      interactions.

PMID- 25370102
TI  - Coordination preferences of the alkali cations sodium and caesium in the mixed
      cationic Zintl ammoniate Cs(3.2)Na(0.8)Ge9.5.3NH3.
AB  - The involvement of two different alkali cations in the nonagermanide ammoniate
      Cs(3.2)Na(0.8)Ge9.5.3NH3 [tricaesium sodium nonagermanide-ammonia (1/5.3)]
      provides insights into the coordination behaviour of ammonia towards sodium and
      caesium cations within one compound and represents the first mixed-cationic
      solvate structure of nonagermanide tetraanions. The compound crystallizes in the
      monoclinic space group P21/m and, with the presence of pseudomerohedral twinning,
      mixed-cation sites and disordering of the nonagermanide cage anions, features a
      combination of crystallographic challenges which could all be resolved during the
      refinement.

PMID- 25370103
TI  - Correlation of the solid-state reactivities of racemic 2,4(6)-di-O-benzoyl-myo
      inositol 1,3,5-orthoformate and its 4,4'-bipyridine cocrystal with their crystal
      structures.
AB  - Racemic 2,4(6)-di-O-benzoyl-myo-inositol 1,3,5-orthoformate, C21H18O8, (1), shows
      a very efficient intermolecular benzoyl-group migration reaction in its crystals.
      However, the presence of 4,4'-bipyridine molecules in its cocrystal,
      C21H18O8.C10H8N2, (1).BP, inhibits the intermolecular benzoyl-group transfer
      reaction. In (1), molecules are assembled around the crystallographic twofold
      screw axis (b axis) to form a helical self-assembly through conventional O-H...O
      hydrogen-bonding interactions. This helical association places the reactive C6-O
      benzoyl group (electrophile, El) and the C4-hydroxy group (nucleophile, Nu) in
      proximity, with a preorganized El...Nu geometry favourable for the acyl transfer
      reaction. In the cocrystal (1).BP, the dibenzoate and bipyridine molecules are
      arranged alternately through O-H...N interactions. The presence of the bipyridine
      molecules perturbs the regular helical assembly of the dibenzoate molecules and
      thus restricts the solid-state reactivity. Hence, unlike the parent dibenzoate
      crystals, the cocrystals do not exhibit benzoyl-transfer reactions. This approach
      is useful for increasing the stability of small molecules in the crystalline
      state and could find application in the design of functional solids.

PMID- 25370104
TI  - The achiral tetrapeptide Z-Aib-Aib-Aib-Gly-OtBu.
AB  - The title achiral peptide N-benzyloxycarbonyl-alpha-aminoisobutyryl-alpha
      aminoisobutyryl-alpha-aminoisobutyrylglycine tert-butyl ester or Z-Aib-Aib-Aib
      Gly-OtBu (Aib is alpha-aminoisobutyric acid, Z is benzyloxycarbonyl, Gly is
      glycine and OtBu indicates the tert-butyl ester), C26H40N4O7, is partly hydrated
      (0.075H2O) and has two different conformations which together constitute the
      asymmetric unit. Both molecules form incipient 310-helices. They differ in the
      relative orientation of the N-terminal protection group and at the C-terminus.
      There are two 4->1 intramolecular hydrogen bonds. 

PMID- 25370105
TI  - The antioxidant methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate.
AB  - The title compound, C18H28O3, was prepared by the reaction of 2,6-di-tert
      butylphenol with methyl acrylate under basic conditions using dimethyl sulfoxide
      as the promoter. The structure of this antioxidant indicates significant strain
      between the ortho tert-butyl substituents and the phenolic OH group. In spite of
      the steric crowding of the OH group, it participates in intermolecular hydrogen
      bonding with the ester carbonyl O atom. 

PMID- 25370106
TI  - A new three-dimensional anionic cadmium(II) dicyanamide network.
AB  - A new cadmium dicyanamide complex, poly[tetramethylphosphonium [MU-chlorido-di-MU
      dicyanamido-kappa(4)N(1):N(5)-cadmium(II)]], [(CH3)4P][Cd(NCNCN)2Cl], was
      synthesized by the reaction of tetramethylphosphonium chloride, cadmium nitrate
      tetrahydrate and sodium dicyanamide in aqueous solution. In the crystal
      structure, each Cd(II) atom is octahedrally coordinated by four terminal N atoms
      from four anionic dicyanamide (dca) ligands and by two chloride ligands. The
      dicyanamide ligands play two different roles in the building up of the structure;
      one role results in the formation of [Cd(dca)Cl]2 building blocks, while the
      other links the building blocks into a three-dimensional structure. The anionic
      framework exhibits a solvent-accessible void of 673.8 A(3), amounting to 47.44%
      of the total unit-cell volume. The cavities in the network are occupied by pairs
      of tetramethylphosphonium cations. 

PMID- 25370107
TI  - In situ single-crystal to single-crystal (SCSC) transformation of the one
      dimensional polymer catena-poly[[diaqua(sulfato)copper(II)]-MU2-glycine] into the
      two-dimensional polymer poly[MU2-glycine-MU4-sulfato-copper(II)].
AB  - The one-dimensional coordination polymer catena-poly[diaqua(sulfato
      kappaO)copper(II)]-MU2-glycine-kappa(2)O:O'], [Cu(SO4)(C2H5NO2)(H2O)2]n, (I), was
      synthesized by slow evaporation under vacuum of a saturated aqueous equimolar
      mixture of copper(II) sulfate and glycine. On heating the same blue crystal of
      this complex to 435 K in an oven, its aspect changed to a very pale blue and
      crystal structure analysis indicated that it had transformed into the two
      dimensional coordination polymer poly[(MU2-glycine-kappa(2)O:O')(MU4-sulfato
      kappa(4)O:O':O'':O'')copper(II)], [Cu(SO4)(C2H5NO2)]n, (II). In (I), the Cu(II)
      cation has a pentacoordinate square-pyramidal coordination environment. It is
      coordinated by two water molecules and two O atoms of bridging glycine
      carboxylate groups in the basal plane, and by a sulfate O atom in the apical
      position. In complex (II), the Cu(II) cation has an octahedral coordination
      environment. It is coordinated by four sulfate O atoms, one of which bridges two
      Cu(II) cations, and two O atoms of bridging glycine carboxylate groups. In the
      crystal structure of (I), the one-dimensional polymers, extending along [001],
      are linked via N-H...O, O-H...O and bifurcated N-H...O,O hydrogen bonds, forming
      a three-dimensional framework. In the crystal structure of (II), the two
      dimensional networks are linked via bifurcated N-H...O,O hydrogen bonds involving
      the sulfate O atoms, forming a three-dimensional framework. In the crystal
      structures of both compounds, there are C-H...O hydrogen bonds present, which
      reinforce the three-dimensional frameworks.

PMID- 25370108
TI  - 2-Ethyl-1-[5-(4-methylphenyl)pyrazol-3-yl]-3-(thiophene-2-carbonyl)isothiourea:
      molecular ribbons containing three types of hydrogen-bonded ring.
AB  - The title compound, C18H18N4OS2, was prepared by reaction of S,S-diethyl 2
      thenoylimidodithiocarbonate with 5-amino-3-(4-methylphenyl)-1H-pyrazole using
      microwave irradiation under solvent-free conditions. In the molecule, the
      thiophene unit is disordered over two sets of atomic sites, with occupancies of
      0.814 (4) and 0.186 (4), and the bonded distances provide evidence for
      polarization in the acylthiourea fragment and for aromatic type delocalization in
      the pyrazole ring. An intramolecular N-H...O hydrogen bond is present, forming an
      S(6) motif, and molecules are linked by N-H...O and N-H...N hydrogen bonds to
      form a ribbon in which centrosymmetric R2(2)(4) rings, built from N-H...O
      hydrogen bonds and flanked by inversion-related pairs of S(6) rings, alternate
      with centrosymmetric R2(2)(6) rings built from N-H...N hydrogen bonds.

PMID- 25370109
TI  - One- and two-dimensional Cd(II) coordination polymers incorporating
      organophosphinate ligands.
AB  - Reaction of cadmium nitrate with diphenylphosphinic acid in dimethylformamide
      solvent yielded the one-dimensional coordination polymer catena
      poly[[bis(dimethylformamide-kappaO)cadmium(II)]-bis(MU-diphenylphosphinato
      kappa(2)O:O')], [Cd(C12H10O2P)2(C3H7NO)2]n, (I). Addition of 4,4'-bipyridine to
      the synthesis afforded a two-dimensional extended structure, poly[[(MU-4,4'
      bipyridine-kappa(2)N:N')bis(MU-diphenylphosphinato-kappa(2)O:O')cadmium(II)]
      dimethylformamide monosolvate], {[Cd(C12H10O2P)2(C10H8N2)].C3H7NO}n, (II). In
      (II), the 4,4'-bipyridine molecules link the Cd(II) centers in the
      crystallographic a direction, while the phosphinate ligands link the Cd(II)
      centers in the crystallographic b direction to complete a two-dimensional sheet
      structure. Consideration of additional pi-pi interactions of the phenyl rings in
      (II) produces a three-dimensional structure with channels that encapsulate
      dimethylformamide molecules as solvent of crystallization. Both compounds were
      characterized by single-crystal X-ray diffraction and FT-IR analysis. 

PMID- 25370110
TI  - Hobartine: a tetracyclic indole alkaloid extracted from Aristotelia chilensis
      (maqui).
AB  - The natural compound hobartine {systematic name: (1R)-3-[(1S,5S)-(4,4,8
      trimethylbicyclo[3.3.1]non-7-en-2-yl)methyl]-2,3-dihydro-1H-indole}, C20H26N2,
      (I), is an indole alkaloid isolated from Aristotelia chilensis as part of a study
      of secondary metabolites from Chilean flora. The colourless compound has a
      tetracyclic structure closely related to the strongly coloured polymorphic
      structures discussed in Paz et al. [Acta Cryst. (2013), C69, 1509-1512] and
      Watson et al. [Acta Cryst. (1989), C45, 1322-1324]. The main differences reside
      in the absence of a keto group in (I) compared with the previous structures, as
      well as an endo double bond in (I) contrasting with the exo double bond found in
      the previous structures. The supramolecular structure of (I) in strongly related
      to the twofold screw axis, around which isolated chains build up, internally
      linked by an N-H...N hydrogen bond which is the only significant intermolecular
      interaction present in the structure.

PMID- 25370111
TI  - A novel two-dimensional Cd(II) coordination polymer: poly[aqua[MU4-2-(4
      carboxylatobenzoyl)benzoato]cadmium(II)].
AB  - The title Cd(II) coordination framework, [Cd(C15H8O5)(H2O)]n or [Cd(bpdc)(H2O)]n
      [H2bpdc is 2-(4-carboxybenzoyl)benzoic acid], has been prepared and characterized
      using IR spectroscopy, elemental analysis, thermal analysis and single-crystal X
      ray diffraction. Each Cd(II) centre is six-coordinated by two O atoms from one 2
      (4-carboxylatobenzoyl)benzoate (bpdc(2-)) ligand in chelating mode, three O-donor
      atoms from three other bpdc(2-) anions and one O atom from a coordinated water
      molecule in an octahedral coordination environment. Two crystallographically
      equivalent Cd(II) cations are bridged by one O atom of the 2-carboxylate group of
      one bpdc(2-) ligand and by both O atoms of the 4-carboxylate group of a second
      bpdc(2-) ligand to form a binuclear [(Cd)2(O)(OCO)] secondary building unit.
      Adjacent secondary building units are interlinked to form a one-dimensional
      [Cd(OCO)2]n chain. The bpdc(2-) ligands link these rod-shaped chains to give rise
      to a complex two-dimensional [Cd(bpdc)]n framework with a 4,4-connected binodal
      net topology of point symbol {4(3).6(2).8}. The compound exhibits a strong
      fluorescence emission and typical ferroelectric behaviour in the solid state at
      room temperature. 

PMID- 25370112
TI  - An azide-bridged copper(II) complex: poly[piperazine-1,4-dium [tetra-MU3-azido
      kappa12N1:N1:N1-hexa-MU2-azido-kappa12N1:N1-di-MU2-azido-kappa4N1:N3
      pentacopper(II)] tetrahydrate].
AB  - A new Cu(II)-azide complex, {(C4H12N2)[Cu5(N3)12].4H2O}n, has been synthesized by
      the reaction of piperazine, Cu(OAc)2.2H2O (OAc is acetate) and NaN3. In the
      structure, MU2-1,1- and MU3-1,1,1-azide anions bridge five Cu(II) cations to form
      a linear pentanuclear cluster unit, which is further linked by MU2-1,1- and MU2
      1,3-azide anions to form a two-dimensional condensed [Cu5(N3)12]n layer. The
      diprotonated piperazine and the solvent water molecules are hydrogen bonded to
      the coordination layers to form a three-dimensional supramolecular network. 

PMID- 25370113
TI  - Hexabromo- and hexaiododisilane: small and simple molecules showing completely
      different crystal structures.
AB  - The title compounds were prepared through dephenylation of hexaphenyldisilane
      with acetyl bromide or acetyl iodide in the presence of the corresponding
      aluminium halide. Both substances were purified via sublimation and, for the
      first time, single crystals of hexabromodisilane, Si2Br6, and a new polymorph of
      hexaiododisilane, Si2I6, could be isolated. Molecules of Si2Br6 are located on a
      special position of site symmetry 2/m with a quarter of a molecule in the
      asymmetric unit. Molecules of Si2I6 are located on a special position of site
      symmetry 3&#772; with a sixth of a molecule in the asymmetric unit. The bond
      lengths of Si2Br6 and Si2I6 are in the usual ranges and both molecules adopt a
      staggered conformation. It is interesting to note that Si2Br6 and Si2I6 do not
      form isomorphous structures. Moreover, an orthorhombic polymorph of the present
      structure of Si2I6 is already known [Jansen & Friede (1996). Acta Cryst. C52,
      1333-1334]. Although the title compounds feature such small and simple molecules
      they show completely different crystal structures.

PMID- 25370114
TI  - Seeing is believing: New York Academy of Medicine's Vesalius 500th year
      celebrations.

PMID- 25370115
TI  - Dr. Robert A. LeVine, 2015 Culture, Medicine and Psychiatry honoree.

PMID- 25370120
TI  - Amino acid bioconjugation via iClick reaction of an oxanorbornadiene-masked
      alkyne with a Mn(I)(bpy)(CO)3-coordinated azide.
AB  - The catalyst-free room temperature iClick reaction of an unsymmetrically 2,3
      disubstituted oxanorbornadiene (OND) as a "masked" alkyne equivalent with
      [Mn(N3)(bpy(CH3,CH3))(CO)3] leads to isolation of a phenylalanine ester
      bioconjugate, in which the model amino acid is linked to the metal moiety via a N
      2-coordinated triazolate formed in a cycloaddition-retro-Diels-Alder (crDA)
      reaction sequence, in a novel approach to bioorthogonal coupling reactions based
      on metal-centered reactivity. 

PMID- 25370121
TI  - DNA nanotubes and helical nanotapes via self-assembly of ssDNA-amphiphiles.
AB  - DNA nanotubes were created using molecular self-assembly of single-stranded DNA
      (ssDNA)-amphiphiles composed of a hydrophobic dialkyl tail and polycarbon spacer
      and a hydrophilic ssDNA headgroup. The nanotube structures were formed by
      bilayers of amphiphiles, with the hydrophobic components forming an inner layer
      that was shielded from the aqueous solvent by an outer layer of ssDNA. The
      nanotubes appeared to form via an assembly process that included transitions from
      twisted nanotapes to helical nanotapes to nanotubes. Amphiphiles that contained
      different ssDNA headgroups were created to explore the effect of the length and
      secondary structure of the ssDNA headgroup on the self-assembly behavior of the
      amphiphiles in the presence and absence of the polycarbon spacer. It was found
      that nanotubes could be formed using a variety of headgroup lengths and
      sequences. The ability to create nanotubes via ssDNA-amphiphile self-assembly
      offers an alternative to the other purely DNA-based approaches like DNA origami
      and DNA tile assembly for constructing these structures and may be useful for
      applications in drug delivery, biosensing, and electronics. 

PMID- 25370122
TI  - The complete mitochondrial genome sequence of a rat 9L glial neoplasms CNS-1 cell
      line.
AB  - We sequenced a complete mitochondrial genome sequence of a rat 9L glial neoplasms
      disease CNS-1 cell line for the first time (Accession No. KM657952). The total
      length of the mitogenome was 16,306 bp and coding 13 protein-coding genes, 2
      ribosomal RNA genes, 22 transfer RNA genes. This mitochondrial genome sequence
      will provide new genetic resource into glial neoplasms disease.

PMID- 25370123
TI  - Crystal structures of wild type and disease mutant forms of the ryanodine
      receptor SPRY2 domain.
AB  - Ryanodine receptors (RyRs) form channels responsible for the release of Ca(2+)
      from the endoplasmic and sarcoplasmic reticulum. The SPRY2 domain in the skeletal
      muscle isoform (RyR1) has been proposed as a direct link with L-type calcium
      channels (CaV1.1), allowing for direct mechanical coupling between plasma
      membrane depolarization and Ca(2+) release. Here we present the crystal
      structures of the SPRY2 domain from RyR1 and RyR2 at 1.34-1.84 A resolution. They
      form two antiparallel beta sheets establishing a core, and four additional
      modules of which several are required for proper folding. A buried disease
      mutation, linked to hypertrophic cardiomyopathy and loss-of-function, induces
      local misfolding and strong destabilization. Isothermal titration calorimetry
      experiments negate the RyR1 SPRY2 domain as the major link with CaV1.1. Instead,
      docking into full-length RyR1 cryo-electron microscopy maps suggests that the
      SPRY2 domain forms a link between the N-terminal gating ring and the clamp
      region. 

PMID- 25370124
TI  - Recombinant human thyrotropin before (131)I therapy in patients with nodular
      goitre: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Recombinant human thyrotropin (rhTSH) can be used to enhance
      radioiodine therapy for shrinking multinodular goitre. The aim of this meta
      analysis was to compare the effectiveness of rhTSH pretreatment and radioiodine
      therapy with that of radioiodine alone for treating benign nodular goitre.
      METHODS: The PubMed, EMBASE, Cochrane Library, Scopus and ClinicalTrials.gov
      databases were searched to identify studies published before September 2014. A
      meta-analysis was performed to calculate the pooled effect size using random
      effects models. The primary outcome was the reduction in thyroid volume.
      Secondary outcomes included thyroid function, extent of tracheal compression,
      radioactive iodine uptake, incidence of hypothyroidism and other complications.
      RESULTS: Nine RCTs including 416 patients were selected. The reductions in
      thyroid volume were significantly greater in the rhTSH pretreatment groups than
      those in the radioiodine alone groups at 12 months (weighted mean difference:
      14.42%; 95% CI: 4.51-24.34% in high-dose rhTSH vs radioiodine alone; weighted
      mean difference: 19.66%; 95% CI: 3.67-35.65% in low-dose rhTSH vs radioiodine
      alone). The incidence of hypothyroidism in the high-dose rhTSH groups was
      significantly higher than that in the radioiodine alone groups. No significant
      difference in the incidence of hypothyroidism occurred between the low-dose rhTSH
      groups and the radioiodine alone groups. CONCLUSIONS: The overall results
      indicated that using rhTSH before radioiodine therapy resulted in a greater
      thyroid volume reduction than radioiodine therapy alone. An increased incidence
      of hypothyroidism was observed in patients receiving high-dose rhTSH. Low-dose
      rhTSH before radioiodine therapy is more efficacious than radioiodine therapy
      alone for treating nontoxic benign thyroid nodules.

PMID- 25370125
TI  - Aripiprazole may be effective as an add-on treatment in bulimic symptoms of
      eating disorders.

PMID- 25370126
TI  - Anandamide is involved in appetite-related amygdala hyperactivations in
      schizophrenia patients treated with olanzapine: a functional magnetic resonance
      imaging study.

PMID- 25370127
TI  - Diketopyrrolopyrrole-porphyrin conjugates with high two-photon absorption and
      singlet oxygen generation for two-photon photodynamic therapy.
AB  - Two-photon photodynamic therapy is a promising therapeutic method which requires
      the development of sensitizers with efficient two-photon absorption and singlet
      oxygen generation. Reported here are two new diketopyrrolopyrrole-porphyrin
      conjugates as robust two-photon absorbing dyes with high two-photon absorption
      cross-sections within the therapeutic window. Furthermore, for the first time the
      singlet-oxygen generation efficiency of diketopyrrolopyrrole-containing systems
      is investigated. A preliminary study on cell culture showed efficient two-photon
      induced phototoxicity. 

PMID- 25370129
TI  - Different genetic impact in the development of renal length and width: a twin
      study.
AB  - BACKGROUND: Ultrasound measurements of renal dimensions are conventionally
      limited to renal length, shape and cortical thickness. These are regarded as
      adequate for normal therapeutic decision-making and volume measurements are
      reserved for a few clinical trials. However, there is no evidence concerning the
      degree to which renal length or volume is independently susceptible to heritable
      and environmental influences. AIM: We aimed to determine whether renal length or
      width (as a surrogate of volume) was more influenced by heritability. METHODS: A
      single operator measured renal length and width in 114 adult monozygotic and same
      sex dizygotic Hungarian twin pairs (mean age 43.6 +/- 16.3 years), using an
      Esaote MyLab 70X ultrasound machine with curved array transducer (1-8 MHz,
      CA431). RESULTS: Analysis of within-pair co-twin correlations adjusted for age
      and gender showed that the age- and sex-adjusted heritability of average renal
      length was 51% (95% confidence interval, 29-72%). Renal width showed negligible
      genetic influence. Common environmental effects had no influence, and unshared
      environments were responsible for 49-80% of the variance, mainly renal width.
      CONCLUSIONS: This study is the first to demonstrate the moderate heritability and
      limited environmental influence on renal length, and the contrasting lack of
      heritability of renal width, which is mainly influenced by unshared environmental
      components, that is lifestyle habits. Renal width therefore better represents the
      influence of modifiable environmental factors than renal length. The results
      suggest that renal width not length should be reported to facilitate early
      detection and monitoring of renal disease.

PMID- 25370133
TI  - The use of rigid endoscopy in the management of acute oropharyngeal stick
      injuries.
AB  - OBJECTIVE: To evaluate the use of rigid endoscopy in the management of
      oropharyngeal stick injuries. METHODS: Retrospective analysis of case records
      between 2011 and 2013 from a large referral hospital. Data regarding signalment,
      clinical presentation, treatment options and final outcomes were recorded.
      RESULTS: Nine dogs were identified with acute oropharyngeal stick injuries. There
      were seven males and two females and the dogs were of various breeds, ages (1 . 5
      to 9 years) and weights (11 . 9 to 38 . 4 kg). The time from injury to referral
      was between 1 and 3 days (median: 2 days). All dogs were anaesthetised and the
      tracts explored using a 30 degrees  forward-oblique, 2 . 7-mm-diameter, 18-cm
      length rigid endoscope with corresponding 14 . 5 Fr sheath. The endoscopy was
      performed under saline irrigation. Foreign material (>1 mm in size) was removed
      using grasping forceps fed through the sheath. Subsequently, the tracts were re
      inspected and flushed with further saline to confirm that all foreign material
      had been removed. All dogs recovered uneventfully and had excellent outcomes with
      no cases representing with chronic manifestations of oropharyngeal stick
      injuries. CLINICAL SIGNIFICANCE: Rigid endoscopy is an effective method for the
      diagnosis, assessment and, in certain cases, treatment of acute oropharyngeal
      stick injuries in dogs.

PMID- 25370137
TI  - Modeling the Trajectory of Analgesic Demand Over Time After Total Knee
      Arthroplasty Using the Latent Curve Analysis.
AB  - OBJECTIVES: Patient-controlled epidural analgesia (PCEA) is commonly used for
      pain relief after total knee arthroplasty (TKA). This study aimed to model the
      trajectory of analgesic demand over time after TKA and explore its influential
      factors using latent curve analysis. METHODS: Data were retrospectively collected
      from 916 patients receiving unilateral or bilateral TKA and postoperative PCEA.
      PCEA demands during 12-hour intervals for 48 hours were directly retrieved from
      infusion pumps. Potentially influential factors of PCEA demand, including age,
      height, weight, body mass index, sex, and infusion pump settings, were also
      collected. A latent curve analysis with 2 latent variables, the intercept
      (baseline) and slope (trend), was applied to model the changes in PCEA demand
      over time. The effects of influential factors on these 2 latent variables were
      estimated to examine how these factors interacted with time to alter the
      trajectory of PCEA demand over time. RESULTS: On average, the difference in
      analgesic demand between the first and second 12-hour intervals was only 15% of
      that between the first and third 12-hour intervals. No significant difference in
      PCEA demand was noted between the third and fourth 12-hour intervals. Aging
      tended to decrease the baseline PCEA demand but body mass index and infusion rate
      were positively correlated with the baseline. Only sex significantly affected the
      trend parameter and male individuals tended to have a smoother decreasing trend
      of analgesic demands over time. Patients receiving bilateral procedures did not
      consume more analgesics than their unilateral counterparts. Goodness of fit
      analysis indicated acceptable model fit to the observed data. CONCLUSIONS: Latent
      curve analysis provided valuable information about how analgesic demand after TKA
      changed over time and how patient characteristics affected its trajectory.

PMID- 25370135
TI  - Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled
      Clinical Trial.
AB  - OBJECTIVES: Compared with pain-free controls, patients with fibromyalgia (FM)
      have more mast cells in the skin. Whether mast cells are involved in the
      pathogenesis of FM is unclear. We sought to determine the effects of a mast cell
      stabilizer (ketotifen) on FM symptoms. MATERIALS AND METHODS: Fifty-one FM
      patients were randomized to daily oral ketotifen 2 mg bid (n=24) for 8 weeks or
      placebo (N=27). Mean age of patients was 51.2 years (SD=8.4); 88% were female and
      88% were white; 22% were taking concomitant opiates; and mean pressure pain
      sensitivity (range, 0 to 20) was 10.0 (0.4). At study entry, the weekly average
      pain intensity was 6.4 (1.1) and the mean score on the Revised Fibromyalgia
      Impact Questionnaire-Revised was 66.8 (14.0). RESULTS: We found no statistically
      significant treatment group differences from baseline in either group for the 2
      primary measures: weekly average pain intensity (ketotifen -1.3 [1.9] vs. placebo
      -1.5 [1.9], P=0.7); and Fibromyalgia Impact Questionnaire-Revised score (-12.1
      [19.5] vs. -12.2 [18.1], P=0.9). No secondary outcome measures (Brief Pain
      Inventory pain intensity and pressure pain sensitivity) reached statistical
      significance; results did not differ in the intent-to-treat and completer
      analyses. Other than transient sedation (6 [28.6%] vs. 1 [4.0%]), ketotifen was
      well tolerated. DISCUSSION: The study results question whether skin mast cells
      play a major role in the pathogenesis of FM. However, given the role of mast
      cells in peripheral and central nociception, and the minimal side effects of
      ketotifen, a randomized clinical trial using increasing doses of ketotifen may be
      warranted.

PMID- 25370136
TI  - The Relationship of Pain and Nausea in Postoperative Patients for 1 Week After
      Ambulatory Surgery.
AB  - OBJECTIVES: The purpose of this study was to determine if pain level was
      associated with demographic or surgery-specific characteristics among patients
      recovering from ambulatory surgery; and to assess the relationship between pain
      level and nausea over the 7-day postoperative period, controlling for demographic
      and surgery-related covariates. MATERIALS AND METHODS: This longitudinal study
      assessed the pain and nausea of 248 eligible patients during the day of surgery
      (DOS) and the 7 days following ambulatory surgery. Postoperative data were
      assessed using standardized questions about severity of pain and nausea symptoms.
      Participants who had a cumulative pain score of >=24 over the 8-day period were
      categorized as having high pain. Repeated-measures analysis of variance was used
      to assess differences in nausea by pain group over time, controlling for
      demographic, surgical variables, and antiemetic and analgesic use. RESULTS: There
      were significant differences between 2 pain groups in age, surgical procedure,
      cumulative morphine equivalent dose, and use of antiemetics postdischarge. The
      longitudinal analysis demonstrated that patients in the high-pain group reported
      a greater degree of nausea on DOS and on each of the first 5 days postsurgery,
      controlling for differences in age, sex, education, use of antiemetics presurgery
      and postsurgery, use of acetaminophen postsurgery, daily morphine equivalent
      dose, and surgical procedure. DISCUSSION: Younger patients and those receiving
      orthopedic procedures may be at greatest risk for postoperative pain. Patients
      with high pain reported a significantly greater degree of nausea on DOS through
      the first 5 days postdischarge. As the majority of surgeries are now conducted in
      the ambulatory setting, it is imperative that we determine pain management
      regimens and patient education practices that will allow for a more comfortable
      recovery for our patients.

PMID- 25370134
TI  - The Medicinal Cannabis Treatment Agreement: Providing Information to Chronic Pain
      Patients Through a Written Document.
AB  - AIM: Pain practitioners would seem to have an obligation to understand and inform
      their patients on key issues of the evidence base on cannabinoid therapeutics.
      One way to fulfill this obligation might be to borrow from concepts developed in
      the prescription of opioids: the use of a written agreement to describe and
      minimize risks. Regrettably, the widespread adoption of opioids was undertaken
      while harmful effects were minimized; obviously, no one wants to repeat this
      misstep. OBJECTIVE: This article describes a method of educating patients in a
      manner analogous to other treatment agreements. BACKGROUND: Surveys have
      demonstrated that pain is the most common indication for medical use of cannabis.
      As more individuals gain access to this botanical product through state ballot
      initiatives and legislative mandate, the pain specialist is likely to be
      confronted by patients either seeking such treatment where permitted, or
      otherwise inquiring about its potential benefits and harms, and alternative
      pharmaceuticals containing cannabinoids. METHODS: PubMed searches were conducted
      using the following keywords: cannabis guidelines, harmful effects of cannabis,
      medical marijuana, medicinal cannabis, opioid cannabis interaction, cannabis
      dependence and cannabis abuse RESULTS: : The authors selected individual tenets a
      medicinal cannabis patient would be asked to review and acknowledge via
      signature. CONCLUSIONS: Undoubtedly, the knowledge base concerning risks will be
      an iterative process as we learn more about the long-term use of medicinal
      cannabis. But we should start the process now so that patients may be instructed
      about our current conception of what the use of medicinal cannabis entails.

PMID- 25370138
TI  - "There's a Pain App for That": Review of Patient-targeted Smartphone Applications
      for Pain Management.
AB  - OBJECTIVES: There are a growing number of pain self-management applications
      (apps) available for users to download on personal smartphones. The purpose of
      this study was to critically appraise the content and self-management
      functionality of currently available pain apps. METHODS: An electronic search was
      conducted between May and June 2014 of the official stores for the 4 major
      operating systems. Two authors independently identified patient-focused apps with
      a stated goal of pain management. Discrepancies regarding selection were resolved
      through discussion with a third party. Metadata from all included apps were
      abstracted into a standard form. The content and functionality of each app as it
      pertained to pain self-management was rated. RESULTS: A total of 279 apps met the
      inclusion criteria. Pain self-care skill support was the most common self
      management function (77.4%). Apps also purported providing patients with the
      ability to engage in pain education (45.9%), self-monitoring (19%), social
      support (3.6%), and goal-setting (0.72%). No apps were comprehensive in terms of
      pain self-management, with the majority of apps including only a single self
      management function (58.5%). In addition, only 8.2% of apps included a health
      care professional in their development, not a single app provided a theoretical
      rationale, and only 1 app underwent scientific evaluation. DISCUSSION: Currently
      available pain self-management apps for patients are simplistic, lack the
      involvement of health care professionals in their development, and have not been
      rigorously tested for effectiveness on pain-related health outcomes. There is a
      need to develop and test theoretically and evidence-based apps to better support
      patients with accessible pain care self-management.

PMID- 25370139
TI  - Pain Management in Neonatal Intensive Care: Evaluation of the Compliance With
      Guidelines.
AB  - BACKGROUND: A pain management protocol was implemented in our neonatal intensive
      care unit in 2005, including individual pain assessments and pain treatment
      guidelines with a decision tree. OBJECTIVES: To prospectively evaluate the degree
      of compliance of medical and nursing staff with the pain protocol. METHODS:
      Prospectively recorded pain scores (COMFORTneo score) and all prescribed
      analgesics and sedatives for the calendar year 2011 were retrieved. The primary
      outcome was the degree of compliance to the protocol with respect to pain
      assessments and treatment; the secondary outcome consisted of reasons for
      noncompliance. RESULTS: Of the 732 included patients, 660 (90%) received fewer
      than the stipulated 3 assessments per day. Eighty-six per cent of all assessments
      yielded a score between 9 and 14, suggesting a comfortable patient. In cases of
      high pain scores (>=14), reassessment within 60 minutes took place in 31% of
      cases and in 40% treatment was started or adjusted. In cases of low pain scores
      (<=8) during treatment, 13% of the 457 assessments were reassessed within 120
      minutes and in 17% a dose reduction was performed. CONCLUSIONS: Although the
      majority of pain assessments suggested comfortable patients, there is room for
      improvement with respect to reassessments after adjustment of analgesic/sedative
      treatment. Some protocol violations such as oversedation in palliative patients
      are acceptable but should be well documented.

PMID- 25370140
TI  - Scrambler Therapy for Chronic Pain.

PMID- 25370141
TI  - Reliability is Necessary but Far From Sufficient: How Might the Validity of Pain
      Ratings be Improved?

PMID- 25370142
TI  - Avoidance and Persistence: Capacity or Motivation?

PMID- 25370143
TI  - A debate on the proposition that self-report is the gold standard in assessment
      of pediatric pain intensity.
AB  - OBJECTIVES AND METHODS: Self-report is often represented as "the gold standard"
      in assessment of pain intensity in children. We evaluate arguments for and
      against this claim and consider its implications for pain management. RESULTS:
      Those in the support of the proposition argue that, when children are able to
      self-report, treatment decisions should be made based on these scores in line
      with current evidence-based recommendations. Pain is a subjective phenomenon and
      can be assessed only via self-report. Treating self-report scores as the gold
      standard is the only valid way for health care professionals to decide on
      appropriate treatment.Those against the proposition contend that reliance on self
      reported pain scores for analgesic treatment decisions is inappropriate as they
      oversimplify the pain experience, yield only marginal information on which to
      base treatment decisions, and potentially place children at significant risk for
      adverse events. Self-reports of pain intensity sometimes contradict well-founded
      estimates based on other evidence. Wide variation between children in the meaning
      of pain scores precludes easy interpretation. DISCUSSION: We conclude that self
      report, when available, can be considered a primary source of evidence about pain
      intensity. However, it cannot be treated as an unquestioned gold standard.
      Instead, hierarchical or bundled approaches should be used, taking into account
      self-report as well as the many individual and contextual factors that influence
      pain including clinical history, patient preferences, and response to previous
      treatments. Alternate models are presented to guide further practice and
      research.

PMID- 25370145
TI  - An adaptive role for negative expected pain in patients with neuropathic pain.
AB  - OBJECTIVES: To study the relationship between expected pain and future outcomes
      along with the moderating effects of expected pain in neuropathic pain patients.
      METHODS: Study participants were recruited for the Canadian Neuropathic Pain
      Database. To examine the relationship between expected pain and 6-month pain
      intensity, pain-related disability, and catastrophizing, multiple regressions
      were performed. These relationships were adjusted for potential confounding (age,
      sex, baseline pain intensity, and psychological distress). To evaluate the
      moderating effect of expected pain on the relationship between baseline pain
      intensity and 6-month outcomes, pain intensity*expected pain interaction terms
      were created. RESULTS: Complete data for analysis was available for 560 patients
      (71%). Expected pain was positively correlated with pain intensity and pain
      related disability scores at 6 months. The relationship between baseline pain
      intensity and 6-month catastrophizing scores was moderated by expected pain
      (however, despite a similar trend, expected pain did not statistically moderate
      the relationship between baseline pain intensity and 6-month pain intensity or
      disability). At higher levels of pain, predicted catastrophizing scores were
      higher for those with low levels of expected pain than those with high levels of
      expected pain. An opposite relationship was observed for patients with the lower
      levels of pain. DISCUSSION: In neuropathic pain patients whose pain does not
      respond to therapy, high levels of expected pain may relate to relatively lower
      catastrophizing scores by shifting focus away from futile attempts at "curing"
      pain toward focusing on achievement of more realistic personal goals.

PMID- 25370144
TI  - Genetic Polymorphisms in the Dopamine Receptor 2 Predict Acute Pain Severity
      After Motor Vehicle Collision.
AB  - OBJECTIVES: Dopaminergic signaling is implicated in nociceptive pathways. These
      effects are mediated largely through dopamine receptors and modulated in part by
      dopamine transporters. This study tested the hypothesis that genetic variants in
      the genes encoding dopamine receptor 2 (DRD2) and the dopamine active transporter
      (SLC6A3) influence acute pain severity after motor vehicle collision. MATERIALS
      AND METHODS: European Americans presenting to the emergency department after
      motor vehicle collision were recruited. Overall pain intensity in emergency
      department was assessed using a 0 to 10 numeric rating scale. DNA was extracted
      from blood samples and genotyping of single-nucleotide polymorphisms (SNPs) in
      the DRD2 and SLC6A3 gene was performed. RESULTS: A total of 948 patients
      completed evaluation. After correction for multiple comparisons, SNP rs6276 at
      DRD2 showed significant association with pain scores, with individuals with the
      A/A genotype reporting lower mean pain scores (5.3; 95% confidence interval [CI],
      5.1-5.5) than those with A/G (5.9; 95% CI, 5.6-6.1) or G/G (5.7; 95% CI, 5.2-6.2)
      genotypes (P=0.0027). Secondary analyses revealed an interaction between sex and
      DRD2 SNPs rs4586205 and rs4648318 on pain scores: females with 2 minor alleles
      had increased pain intensity, whereas males with 2 minor alleles had less pain
      than individuals with a major allele (interaction P=0.0019). DISCUSSION: Genetic
      variants in DRD2 are associated with acute pain after a traumatic stressful
      event. These results suggest that dopaminergic agents may be useful for the
      treatment of individuals with acute posttraumatic pain as part of a multimodal
      opioid-sparing analgesic regimen.

PMID- 25370146
TI  - Avoidance or Incapacitation: A Discussion on Definition and Validity of Objective
      Measures of Avoidance, Persistence, and Overactivity.

PMID- 25370147
TI  - Intranasal Oxytocin Administration is Associated With Enhanced Endogenous Pain
      Inhibition and Reduced Negative Mood States.
AB  - OBJECTIVES: This study examined whether the administration of intranasal oxytocin
      was associated with pain sensitivity, endogenous pain inhibitory capacity, and
      negative mood states. MATERIALS AND METHODS: A total of 30 pain-free, young
      adults each completed 3 laboratory sessions on consecutive days. The first
      session (baseline) assessed ischemic pain sensitivity, endogenous pain inhibition
      via conditioned pain modulation (CPM), and negative mood using the Profile of
      Mood States. CPM was tested on the dominant forearm and ipsilateral masseter
      muscle using algometry (test stimulus) and the cold pressor task (conditioning
      stimulus; nondominant hand). For the second and third sessions, participants
      initially completed the State-Trait Anxiety Inventory and then self-administered
      a single (40 IU/1 mL) dose of intranasal oxytocin or placebo in a randomized
      counterbalanced order. Thirty minutes postadministration, participants again
      completed the State-Trait Anxiety Inventory and repeated assessments of ischemic
      pain sensitivity and CPM followed by the Profile of Mood States. RESULTS:
      Findings demonstrated that ischemic pain sensitivity did not significantly differ
      across the 3 study sessions. CPM at the masseter, but not the forearm, was
      significantly greater following administration of oxytocin compared to placebo.
      Negative mood was also significantly lower following administration of oxytocin
      compared to placebo. Similarly, anxiety significantly decreased following
      administration of oxytocin but not placebo. DISCUSSION: This study incorporated a
      placebo-controlled, double-blind, within-subjects crossover design with
      randomized administration of intranasal oxytocin and placebo. The data suggest
      that the administration of intranasal oxytocin may augment endogenous pain
      inhibitory capacity and reduce negative mood states including anxiety.

PMID- 25370148
TI  - Investigation of the caspase-dependent mitochondrial apoptotic pathway in
      mononuclear cells of patients with systemic Lupus erythematosus.
AB  - BACKGROUND: This study aimed to explore the role of apoptosis initiators, caspase
      9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon
      regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE).
      METHODS: Leukocyte apoptosis was determined by flow cytometry, including annexin
      V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35
      patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels
      of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease
      activity index (SLEDAI) in the SLE patients were determined. Correlation among
      intracellular adaptor proteins and caspase levels were calculated. RESULTS: The
      SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and
      higher late apoptosis markers in total leukocytes and neutrophils than normal
      controls (all p < 0.05). Disease activity was positively associated with the
      APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9
      levels (all p < 0.05). Markers of viral infection and anti-virus transcription
      factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than
      in disease controls (p < 0.05). Caspase-9 and caspase-10 levels positively
      correlated with MAVS and pIRF7 in SLE patients (p < 0.05). CONCLUSIONS: The
      disease activity of SLE is positively associated with APO2.7 level of CD19+ cells
      but negatively associated with MAVS and caspase-9 levels, which all point to a
      mitochondrial pathway.

PMID- 25370149
TI  - Clinical accuracy of a continuous glucose monitoring system with an advanced
      algorithm.
AB  - We assessed the performance of a modified Dexcom G4 Platinum system with an
      advanced algorithm, in comparison with frequent venous samples measured on a
      laboratory reference (YSI) during a clinic session and in comparison to self
      monitored blood glucose (SMBG) during home use. Fifty-one subjects with diabetes
      were enrolled in a prospective multicenter study. Subjects wore 1 sensor for 7
      day use and participated in one 12-hour in-clinic session on day 1, 4, or 7 to
      collect YSI reference venous glucose every 15 minutes and capillary SMBG test
      every 30 minutes. Carbohydrate consumption and insulin dosing and timing were
      manipulated to obtain data in low and high glucose ranges. In comparison with the
      laboratory reference method (n = 2,263) the system provided a mean and median
      absolute relative differences (ARD) of 9.0% and 7.0%, respectively. The mean
      absolute difference for CGM was 6.4 mg/dL when the YSIs were within hypoglycemia
      ranges (<= 70 mg/dL). The percentage in the clinically accurate Clarke error grid
      A zone was 92.4% and in the benign error B zone was 7.1%. Majority of the sensors
      (73%) had an aggregated MARD in reference to YSI <= 10%. The MARD of CGM-SMBG for
      home use was 11.3%. The study showed that the point and rate accuracy, clinical
      accuracy, reliability, and consistency over the duration of wear and across
      glycemic ranges were superior to current commercial real-time CGM systems. The
      performance of this CGM is reaching that of a self-monitoring blood glucose meter
      in real use environment. 

PMID- 25370151
TI  - Redox-active multinuclear Pd(II) complexes with bis- and tris-mesoionic carbenes.
AB  - Synthesis of a ligand platform to generate di- and tri-mesoionic carbenes is
      reported together with their multinuclear Pd(II) complexes. Complete structural
      characterization and preliminary electrochemical data are presented.

PMID- 25370150
TI  - The effect of fluorescent nanodiamonds on neuronal survival and morphogenesis.
AB  - Nanodiamond (ND) has emerged as a promising carbon nanomaterial for therapeutic
      applications. In previous studies, ND has been reported to have outstanding
      biocompatibility and high uptake rate in various cell types. ND containing
      nitrogen-vacancy centers exhibit fluorescence property is called fluorescent
      nanodiamond (FND), and has been applied for bio-labeling agent. However, the
      influence and application of FND on the nervous system remain elusive. In order
      to study the compatibility of FND on the nervous system, neurons treated with
      FNDs in vitro and in vivo were examined. FND did not induce cytotoxicity in
      primary neurons from either central (CNS) or peripheral nervous system (PNS);
      neither did intracranial injection of FND affect animal behavior. The neuronal
      uptake of FNDs was confirmed using flow cytometry and confocal microscopy.
      However, FND caused a concentration-dependent decrease in neurite length in both
      CNS and PNS neurons. Time-lapse live cell imaging showed that the reduction of
      neurite length was due to the spatial hindrance of FND on advancing axonal growth
      cone. These findings demonstrate that FNDs exhibit low neuronal toxicity but
      interfere with neuronal morphogenesis, and should be taken into consideration
      when applications involve actively growing neurites (e.g. nerve regeneration). 

PMID- 25370153
TI  - Accelerometer-based measures in physical activity surveillance: current practices
      and issues.
AB  - OBJECTIVE: Self-reports of physical activity (PA) have been the mainstay of
      measurement in most non-communicable disease (NCD) surveillance systems. To
      these, other measures are added to summate to a comprehensive PA surveillance
      system. Recently, some national NCD surveillance systems have started using
      accelerometers as a measure of PA. The purpose of this paper was specifically to
      appraise the suitability and role of accelerometers for population-level PA
      surveillance. METHODS: A thorough literature search was conducted to examine
      aspects of the generalisability, reliability, validity, comprehensiveness and
      between-study comparability of accelerometer estimates, and to gauge the
      simplicity, cost-effectiveness, adaptability and sustainability of their use in
      NCD surveillance. CONCLUSIONS: Accelerometer data collected in PA surveillance
      systems may not provide estimates that are generalisable to the target
      population. Accelerometer-based estimates have adequate reliability for PA
      surveillance, but there are still several issues associated with their validity.
      Accelerometer-based prevalence estimates are largely dependent on the
      investigators' choice of intensity cut-off points. Maintaining standardised
      accelerometer data collections in long-term PA surveillance systems is difficult,
      which may cause discontinuity in time-trend data. The use of accelerometers does
      not necessarily produce useful between-study and international comparisons due to
      lack of standardisation of data collection and processing methods. To conclude,
      it appears that accelerometers still have limitations regarding generalisability,
      validity, comprehensiveness, simplicity, affordability, adaptability, between
      study comparability and sustainability. Therefore, given the current evidence, it
      seems that the widespread adoption of accelerometers specifically for large-scale
      PA surveillance systems may be premature.

PMID- 25370152
TI  - Novel, high incidence exercise-induced muscle bleeding model in hemophilia B
      mice: rationale, development and prophylactic intervention.
AB  - INTRODUCTION: Muscle hematomas are the second most common complication of
      hemophilia and insufficient treatment may result in serious and even life
      threatening complications. Hemophilic dogs and rats do experience spontaneous
      muscle bleeding, but currently, no experimental animal model is available
      specifically investigating spontaneous muscle bleeds in a hemophilic setting.
      AIM: The objective of this study was to develop a model of spontaneous muscle
      bleeds in hemophilia B mice. We hypothesized that treadmill exercise would induce
      muscle bleeds in hemophilia B mice but not in normal non-hemophilic mice and that
      treatment with recombinant factor IX (rFIX) before treadmill exercise could
      prevent the occurrence of pathology. METHODS: A total of 203 mice (123 F9-KO and
      80 C57BL/6NTac) were included in three separate studies: (i) the model
      implementation study investigating the bleeding pattern in hemophilia B mice
      after treadmill exercise; (ii) a study evaluating the pharmacokinetics of
      recombinant FIX (rFIX) in hemophilia B mice and based on these data; (iii) the
      treatment study, which tested therapeutic intervention with rFIX. At termination
      of the treadmill studies the presence of bleeds was evaluated. RESULTS: Treadmill
      exercise resulted in a high incidence of muscle bleeds in F9-KO mice but not in
      C57BL/6NTac mice. Treating hemophilia B mice with rFIX before treadmill exercise
      prevented muscle bleeds. CONCLUSION: A novel model of muscle bleeds in hemophilia
      B mice, responsive to rFIX, has been developed.

PMID- 25370154
TI  - Effects of a carotid covered stent with a novel membrane design on the blood flow
      regime and hemodynamic parameters distribution at the carotid artery bifurcation.
AB  - We have recently developed a novel membrane design for carotid covered stents
      that prevents emboli while preserving the external carotid artery (ECA) branch
      flow. Our earlier in vitro studies have shown that this novel design can maintain
      more than 83 % of the original ECA flow and has the potential to considerably
      reduce the chance of emboli release as compared to bare metal stents. In the
      present study, utilizing computational fluid dynamics simulations and fluid
      structure interaction analyses, we further investigated the influence of this
      novel covered stent on the blood flow regime and distribution of hemodynamic
      parameters at the carotid artery bifurcation and within the branches. Simulation
      results of the effect of the covered stent on the flow division at the carotid
      bifurcation were comparable with the earlier experimental results and further
      verified that this covered stent can considerably preserve the ECA flow. The
      results also showed that this covered stent may affect the flow regime and the
      distribution of hemodynamic parameters at the opening of the ECA branch and at
      the apex of the divider wall. These altered local hemodynamic characteristics may
      promote the post-stenting patency of the ECA branch. Evaluation of shear-induced
      platelet activation suggested that activation of platelets due to the blood flow
      through this membrane is unlikely. However, some slow-flow regions near the stent
      membrane around the ECA opening may induce platelet aggregation and thrombus
      formation. This study further demonstrated the potential of this novel covered
      stent design for the treatment of carotid atherosclerotic stenosis. Future in
      vivo investigations of the biological effects and mechanical performance of this
      covered-stent design (e.g., its thrombogenicity potential and biocompatibility)
      are warranted.

PMID- 25370156
TI  - Trans-anal exteriorisation of colon and delayed colo-anal anastomosis for
      sphincter preservation in low carcinoma rectum.

PMID- 25370157
TI  - Porous single-crystalline palladium nanoflowers with enriched {100} facets for
      highly enhanced ethanol oxidation.
AB  - Palladium porous single-crystalline nanoflowers (PSNFs) with enriched high
      catalytic activity {100} facets were synthesized using a mild and controllable
      seed mediated growth method. The growth mechanism of the Pd PSNFs was
      investigated using time dependent morphology evolution through TEM imaging. Due
      to the specific structure, Pd PSNFs show highly enhanced ethanol oxidation
      reaction (EOR) activity, high EOR anti-poisoning and stability, much better than
      Pd nanocubes, {111} facets dominated dendritic urchin-like Pd nanoparticles and
      Pd black. 

PMID- 25370155
TI  - Probiotics prevent Hirschsprung's disease-associated enterocolitis: a prospective
      multicenter randomized controlled trial.
AB  - BACKGROUND: Enterocolitis (EC) is the most common and serious postoperative
      complication of Hirschsprung's disease (HD). Probiotics potentially play a
      protective role in maintaining intestinal mucosal integrity. Based on the
      beneficial effects of probiotics, we hypothesized that oral probiotics could
      decrease the incidence and severity of Hirschsprung's disease-associated
      enterocolitis (HAEC). METHODS: We conducted a prospective, multicenter,
      randomized, and controlled trial to assess whether oral probiotics could decrease
      the incidence and severity of HAEC. HD patients were randomly assigned into the
      control group and probiotic-treated group. All children in probiotic-treated
      group were fed with probiotics per day for 4 weeks. In next 3 months, the
      incidence and severity of HAEC were analyzed. The peripheral blood T lymphocyte
      subsets and cytokines, including TNF-alpha, IFN-gamma, IL-6, and IL-10, were
      analyzed by flow cytometry and enzyme immunoassay (EIA). RESULTS: Compared with
      the control group, the incidence of HAEC in the probiotic-treated group was
      significantly diminished. The severity of EC was also remarkably decreased.
      Furthermore, probiotics balanced T lymphocyte subsets. Moreover, pro-inflammatory
      cytokines TNF-alpha, IFN-gamma, and IL-6 were significantly decreased and anti
      inflammatory cytokine IL-10 was notably increased in probiotic-treated group.
      CONCLUSIONS: Probiotics not only significantly diminished the incidence but also
      decreased the severity of HAEC. Moreover, our study revealed that probiotics
      decreased pro-inflammatory cytokine and increased anti-inflammatory cytokine and
      furthermore balanced T lymphocytes (registered with ClinicalTrials.gov, NCT
      number: NCT01934959).

PMID- 25370159
TI  - Suckling induces a daily rhythm in the preoptic area and lateral septum but not
      in the bed nucleus of the stria terminalis in lactating rabbit does.
AB  - Maternal behavior in the rabbit is restricted to a brief nursing period every
      day. Previously, we demonstrated that this event induces daily rhythms of Period1
      (PER1) protein, the product of the clock gene Per1, in oxytocinergic and
      dopaminergic populations in the hypothalamus of lactating rabbit does. This is
      significant for the periodic production and ejection of milk, but the activation
      of other areas of the brain has not been explored. Here, we hypothesised that
      daily suckling would induce a rhythm in the preoptic area, lateral septum, and
      bed nucleus of the stria terminalis, which are important areas for the expression
      of maternal behavior in mammals, including the rabbit. To this end, we analysed
      PER1 expression in those areas through a complete 24-h cycle at lactation day 7.
      Does were scheduled to nurse during either the day at 10:00 h [zeitgeber time
      (ZT)03] or the night at 02:00 h (ZT19). Non-pregnant, non-lactating females were
      used as controls. In contrast to control females, lactating does showed a clear,
      significant rhythm of PER1 that shifted in parallel with the timing of nursing in
      the preoptic area and lateral septum. We determined that the maximal expression
      of PER1 at 8 h after scheduled nursing decreased significantly at 24 and 48 h
      after the absence of suckling. This effect was more pronounced in the lateral
      septum than in the preoptic area. We conclude that daily suckling is a powerful
      stimulus inducing rhythmic activity in brain structures in the rabbit that appear
      to form part of a maternal entrainable circuit.

PMID- 25370160
TI  - Dolphin: a tool for automatic targeted metabolite profiling using 1D and 2D (1)H
      NMR data.
AB  - One of the main challenges in nuclear magnetic resonance (NMR) metabolomics is to
      obtain valuable metabolic information from large datasets of raw NMR spectra in a
      high throughput, automatic, and reproducible way. To date, established software
      packages used to match and quantify metabolites in NMR spectra remain mostly
      manually operated, leading to low resolution results and subject to
      inconsistencies not attributable to the NMR technique itself. Here, we introduce
      a new software package, called Dolphin, able to automatically quantify a set of
      target metabolites in multiple sample measurements using an approach based on 1D
      and 2D NMR techniques to overcome the inherent limitations of 1D (1)H-NMR spectra
      in metabolomics. Dolphin takes advantage of the 2D J-resolved NMR spectroscopy
      signal dispersion to avoid inconsistencies in signal position detection,
      enhancing the reliability and confidence in metabolite matching. Furthermore, in
      order to improve accuracy in quantification, Dolphin uses 2D NMR spectra to
      obtain additional information on all neighboring signals surrounding the target
      metabolite. We have compared the targeted profiling results of Dolphin, recorded
      from standard biological mixtures, with those of two well established approaches
      in NMR metabolomics. Overall, Dolphin produced more accurate results with the
      added advantage of being a fully automated and high throughput processing
      package. 

PMID- 25370161
TI  - Rapid determination of retinoic acid and its main isomers in plasma by second
      order high-performance liquid chromatography data modeling.
AB  - This paper reports the development of a method based on high-performance liquid
      chromatography (HPLC) coupled to second-order data modeling with multivariate
      curve resolution-alternating least-squares (MCR-ALS) for quantification of
      retinoic acid and its main isomers in plasma in only 5.5 min. The compounds
      retinoic acid (RA), 13-cis-retinoic acid, 9-cis-retinoic acid, and 9,13-di-cis
      retinoic acid were partially separated by use of a Poroshell 120 EC-C18 (3.0 mm *
      30 mm, 2.7 MUm particle size) column. Overlapping not only among the target
      analytes but also with the plasma interferents was resolved by exploiting the
      second-order advantage of the multi-way calibration. A validation study led to
      the following results: trueness with recoveries of 98.5-105.9 % for RA, 95.7
      110.1 % for 13-cis-RA, 97.1-110.8 % for 9-cis-RA, and 99.5-110.9 % for 9,13-di
      cis-RA; repeatability with RSD of 3.5-3.1 % for RA, 3.5-1.5 % for 13-cis-RA, 4.6
      2.7 % for 9-cis-RA, and 5.2-2.7 % for 9,13-di-cis-RA (low and high levels); and
      intermediate precision (inter-day precision) with RSD of 3.8-3.0 % for RA, 2.9
      2.4 % for 13-cis-RA, 3.6-3.2 % for 9,13-di-cis-RA, and 3.2-2.9 % for 9-cis-RA
      (low and high levels). In addition, a robustness study revealed the method was
      suitable for monitoring patients with dermatological diseases treated with
      pharmaceutical products containing RA and 13-cis-RA. 

PMID- 25370162
TI  - A new approach for automated liquid-liquid extraction in a sequential injection
      manifold.
AB  - A new approach for the implementation of liquid-liquid extraction in a sequential
      injection manifold is presented. The manifold consists of two syringe pumps and
      one multi-position valve. The use of a 30 % MeOH/H2O (v/v) solution as the
      carrier, with isobutanol as the extractant, made it possible to avoid the
      problems associated with the different affinities of the organic and aqueous
      phases for Teflon tubing, and the formation of bubbles. The suitability of the
      proposed method was demonstrated by the determination of thiamine in
      pharmaceutical preparations and dietary supplements. Detection and quantification
      limits were estimated as 9 and 30 MUg L(-1), respectively. The repeatability was
      lower than 3 % and the intermediate precision (3 d) was lower than 7 %. The
      sample throughput was 14 samples per h. The results were in agreement with a high
      performance liquid chromatography-electrospray/mass spectrometry reference
      method. 

PMID- 25370163
TI  - Determination of polyphenolic profiles by liquid chromatography-electrospray
      tandem mass spectrometry for the authentication of fruit extracts.
AB  - Liquid chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS/MS) was
      applied to the analysis and authentication of fruit-based products and fruit
      based pharmaceutical preparations. A Kinetex C18 reversed-phase column under
      gradient elution with 0.1 % formic acid aqueous solution and methanol mobile
      phases was used for the simultaneous determination of 26 polyphenols, allowing an
      acceptable separation in less than 22 min. Instrumental quality parameters such
      as limits of detection (LOD, values between 12 and 14 MUg/L for 19 of the 26
      analyzed polyphenols), linearity (r (2) > 0.991), run-to-run and day-to-day
      precisions (relative standard deviation (RSD) values lower than 9.9 and 13.5 %,
      respectively), and accuracy (relative errors lower than 8 %) were established. A
      simple extraction method, consisting of a sample sonication with
      acetone/water/hydrochloric acid (70:29.9:0.1 v/v/v) and centrifugation, was
      proposed. Two calibration procedures, external calibration using standards
      prepared in water and standard addition, were evaluated for polyphenol
      quantification in several grape and cranberry fruits and processed fruit
      products. For a 95 % confidence level, no statistical differences were observed
      between the two calibration methods (p values between 0.06 and 0.95), denoting
      that external calibration was suitable enough for the quantitative analysis of
      polyphenols in fruit-based products. The proposed LC-ESI-MS/MS method was then
      applied to the analysis of polyphenols in 23 grape-based and cranberry-based
      natural products and pharmaceutical preparations. Polyphenolic concentration data
      was then analyzed by principal component analysis (PCA) to extract information of
      the most significant profile data contributing to authentication of natural
      extracts according to their fruit of origin. 

PMID- 25370164
TI  - Barriers and Facilitators for Being Physically Active in Patients with Ankylosing
      Spondylitis: A Cross-sectional Comparative Study.
AB  - OBJECTIVES: The aims of the present study were to explore the barriers and
      facilitators for being physically active and the perceived health benefits of
      physical activity in a group of patients with ankylosing spondylitis (AS), and to
      compare the findings with those in population controls. METHODS: A total of 148
      patients and 133 controls were included in a cross-sectional study. Barriers,
      facilitators and perceived health benefits were registered in a structured
      interview. RESULTS: Patients were significantly more likely to report barriers to
      being physically active compared with controls (78% versus 58%; p <= 0.001). The
      barriers most frequently reported by patients were pain (48%), stiffness (36%),
      fatigue (30%) and disability (21%). A similar proportion of patients (62%) and
      controls (61%) reported that they had the potential to become more physically
      active (p = 0.12). Time and motivation were the most frequently reported
      facilitators in both groups. Patients also reported stable disease (15%) and
      individually adapted physical activity (8%) as facilitators. An equal proportion
      of patients (96%) and controls (96%) reported that physical activity had a
      positive effect on their health (p = 0.94). Improved fitness and increased
      vitality were the most frequently reported health benefits in both groups.
      Patients also reported greater disease stability (37%) and reduced pain (33%) as
      benefits. CONCLUSIONS: A larger proportion of patients than controls reported
      barriers to being physically active. In addition to regular barriers,
      facilitators and health benefits, patients reported that disease-related factors
      influenced their participation in physical activity.

PMID- 25370158
TI  - Divergent transcriptional patterns are related to differences in hypoxia
      tolerance between the intertidal and the subtidal sculpins.
AB  - Transcriptionally mediated phenotypic plasticity as a mechanism of modifying
      traits in response to an environmental challenge remains an important area of
      study. We compared the transcriptional responses to low oxygen (hypoxia) of the
      hypoxia-tolerant intertidal fish, the tidepool sculpin (Oligocottus maculosus)
      with the closely related hypoxia-intolerant subtidal fish, the silverspotted
      sculpin (Blepsias cirrhosus) to determine whether these species use different
      mechanisms to cope with hypoxia. Individuals from each species were exposed to
      environmental O(2) tensions chosen to yield a similar level of tissue hypoxia,
      and gene transcription was assessed in the liver over time. There was an effect
      of time in hypoxia, where the greatest transcriptional change in the
      silverspotted sculpin occurred between 3 and 24 h in contrast to the tidepool
      sculpin where the largest transcriptional change occurred between 24 and 72 h of
      hypoxia. A number of genes showed similar hypoxia-induced transcription patterns
      in both species (e.g. genes associated with glycolysis and apoptosis) suggesting
      they are involved in a conserved hypoxia response. A large set of genes showed
      divergent transcriptional patterns in the two species, including fatty acid
      oxidation and oxidative phosphorylation, suggesting that these biological
      processes may contribute to explaining variation in hypoxia tolerance in these
      species. When both species were exposed to a single environmental O(2) tension,
      large transcriptional responses were seen in the hypoxia-intolerant silverspotted
      sculpin while almost no response was observed in the hypoxia-tolerant tidepool
      sculpin. Overall, divergent transcription patterns in response to both magnitude
      and duration of hypoxia provide insights into the processes that may determine an
      animal's capacity to tolerate frequent bouts of hypoxia in the wild.

PMID- 25370165
TI  - Aortic bypass and orthotopic right renal autotransplantation for midaortic
      syndrome: a case report.
AB  - BACKGROUND: Midaortic syndrome (MAS) is a rare vascular anomaly characterized by
      segmental narrowing of the distal descending thoracic or abdominal aorta. Renal
      or visceral arteries may also be affected to varying degrees. MAS is often
      associated with renovascular hypertension, and requires early intervention. When
      medical therapy and percutaneous interventions fail to control hypertension,
      surgical treatment is required. We report a case of MAS that failed to respond to
      bilateral renal artery stenting, but treated with aortic bypass and orthotopic
      right renal autotransplantation with good outcome. CASE PRESENTATION: A 31-year
      old woman presented with headache and poorly controlled hypertension due to
      severe MAS. She had severe ostial stenoses of renal and visceral arteries. Her
      hypertension failed to respond to medical therapy (four drugs) and bilateral
      renal artery stenting. The implanted stent in the right renal artery rendered
      revascularization of the artery difficult. A one-stage revascularization was
      performed, which consisted of an aortoaortic bypass (between the suprarenal and
      infrarenal abdominal aorta) with a prosthetic graft, an orthotopic right renal
      autotransplantation and an aorto-left renal arterial bypass with autogenous
      saphenous vein grafts. Her recovery was uneventful. At 1-year follow-up, the
      patient remained well. Her hypertension improved. A postoperative computed
      tomography angiography showed that all the grafts were patent with no
      abnormalities at the anastomosis. CONCLUSION: Multiple bypass surgery with
      reimplantation of autogenous vein graft onto the prosthetic graft is a feasible
      and effective procedure in renal artery revascularization for MAS. Orthotopic
      autotransplantation is the procedure of choice in complex renal artery
      reconstruction.

PMID- 25370166
TI  - Aspirin-triggered lipoxin prevents antiphospholipid antibody effects on human
      trophoblast migration and endothelial cell interactions.
AB  - OBJECTIVE: Antiphospholipid antibodies (aPL) interfere with several physiologic
      functions of human trophoblasts, including reducing their ability to migrate,
      decreasing their production of angiogenic factors, and inducing an inflammatory
      response. This may provide the underlying mechanism by which aPL responses lead
      to recurrent pregnancy loss or preeclampsia in women with obstetric
      antiphospholipid syndrome (APS). Although treatment with heparin may reduce the
      rate of recurrent pregnancy loss, the risk of preeclampsia remains high.
      Therefore, alternative treatments are needed for the management of pregnant
      patients with APS. Since aspirin-triggered lipoxins (ATLs) have immune and
      angiogenic modulatory properties, the objective of this study was to determine
      the effects of the ATL 15-epi-lipoxin A4 on the function of aPL-altered human
      trophoblasts in the first trimester of pregnancy. METHODS: A first-trimester
      human trophoblast cell line (HTR8) was treated with mouse anti-human beta2 
      glycoprotein I monoclonal antibodies (aPL) in the presence or absence of the ATL
      15-epi-lipoxin A4 . Trophoblast migration and interactions with endometrial
      endothelial cells were measured using Transwell and coculture assays. Trophoblast
      secretion of cytokines and angiogenic factors was measured by enzyme-linked
      immunosorbent assay. RESULTS: Treatment of HTR8 cells with ATL reversed the aPL
      induced decrease in trophoblast migration, an effect that appeared to be
      regulated through restoration of interleukin-6 production. Using a model of
      spiral artery transformation, aPL and sera from APS patients with pregnancy
      morbidity disrupted trophoblast-endothelial cell interactions, and treatment with
      ATL restored the stability of the cocultures. In contrast, ATL treatment did not
      resolve the proinflammatory and antiangiogenic responses of trophoblasts induced
      by aPL. CONCLUSION: These findings indicate that ATLs may have some benefits in
      terms of preventing the effects of aPL on trophoblast function, which raises the
      possibility of the use of ATLs as an adjuvant therapy in women with aPL.

PMID- 25370167
TI  - Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and
      glutathione depletion.
AB  - Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anti-cancer
      drug. In the present study, the anti-growth effect of Au on HeLa cervical cancer
      cells was examined in association with levels of reactive oxygen species (ROS)
      and glutathione (GSH). Au inhibited the growth of HeLa cells with an IC50 of ~2
      uM at 24 h. This agent induced apoptosis and necrosis, accompanied by the
      cleavage of poly (ADP-ribose) polymerase and loss of mitochondrial membrane
      potential. The pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone, prevented apoptotic cell death and each of the assessed
      caspase inhibitors inhibited necrotic cell death induced by Au. With respect to
      the levels of ROS and GSH, Au increased intracellular O2*- in the HeLa cells and
      induced GSH depletion. The pan-caspase inhibitor reduced the levels of O2*- and
      GSH depletion in Au-treated HeLa cells. The antioxidant, N-acetyl cysteine, not
      only attenuated apoptosis and necrosis in the Au-treated HeLa cells, but also
      decreased the levels of O2*- and GSH depletion in the cells. By contrast, L
      buthionine sulfoximine, a GSH synthesis inhibitor, intensified cell death O2*-
      and GSH depletion in the Au-treated HeLa cells. In conclusion, Au induced
      apoptosis and necrosis in HeLa cells via the induction of oxidative stress and
      the depletion of GSH.

PMID- 25370168
TI  - Evolution from WHO to EASL and mRECIST for hepatocellular carcinoma:
      considerations for tumor response assessment.
AB  - Radiological response assessment criteria in hepatocellular carcinoma (HCC) have
      evolved to accurately evaluate tumor responses. The WHO criteria and the
      subsequent Response Evaluation Criteria in Solid Tumors (RECIST) evaluate change
      in tumor size; however, these criteria generally ignore tumor necrosis and
      therefore may underestimate treatment responses. Thus, a panel of experts of the
      European Association for the Study of Liver (EASL) amended the response criteria
      to take into account tumor necrosis. In 2010, the modified RECIST (mRECIST) was
      developed, which consider both the concept of tumor viability based on arterial
      enhancement and single linear summation, ultimately simplifying EASL criteria.
      Currently, the mRECIST represents the gold standard for radiologically evaluating
      tumor response during HCC treatment. Here, the authors review application and
      performance of mRECIST as well as other HCC response assessment criteria and
      discuss unmet and open issues regarding response evaluation for HCC treatments. 

PMID- 25370170
TI  - [Medical devices. Regulatory framework and contribution of the German Federal
      Institute for Drugs and Medical Devices (BfArM) to the safe application].
AB  - Medical devices are of great importance for the prevention, diagnosis and
      treatment of many diseases. With their broad range and interdisciplinarity, they
      represent both a very dynamic field of innovation and a significant sector of the
      economy. The European and thus the German Medical Devices Act aim in this context
      to make new medical devices for patients and users rapidly available while
      ensuring safety and performance at the same time. The main responsibility for
      this lies with the manufacturer. In addition, others are involved in a complex
      collaboration in the conformity assessment and also later in the marketing phase
      for the early identification, assessment and minimization of potential risks.
      This paper presents the legal framework for medical devices and the related roles
      and responsibilities of various stakeholders, especially the two federal agencies
      the German Federal Institute for Drugs and Medical Devices (BfArM) and the Paul
      Ehrlich Institute (PEI). From the perspective of the BfArM the procedure and
      criteria for risk assessment of incident reports are explained and the
      experiences and wishes from regulatory practice are described. The active
      engagement of the BfArM to contribute knowledge from the incident report
      assessment within the relevant standards organisations and the medical profession
      is described using examples of medical devices from the field of out-of-hospital
      ventilation. The paper concludes with a look at future challenges, e.g. in
      combination products, IT networks and automatization, as well as on current
      developments to improve risk identification and assessment in a European context.

PMID- 25370171
TI  - Characteristics favouring a delayed disposition decision in the emergency
      department.
AB  - BACKGROUND: The working hours of a hospital affects efficiency of care within the
      emergency department (ED). Understanding the influences on ED time intervals is
      crucial for process redesign to improve ED patient flow. AIM: To assess
      characteristics that affect patients' transit through an ED. METHODS:
      Retrospective cohort study from 2004 to 2010 of 268 296 adult patients who
      presented to the ED of an urban tertiary-referral Australian teaching hospital.
      RESULTS: After adjustment for Australasian Triage Scale (ATS) category, every
      decade increase in age meant patients spent an additional 2 min in the ED waiting
      to be seen (P < 0.001) and an extra 29-min receiving treatment (P < 0.001). For
      every additional 10 patients in the ED, the 'waiting time' (WT) phase duration
      increased by 20 min (P < 0.001) and the 'Assessment and Treatment Time' (ATT)
      phase duration increased by 26 min (P < 0.001). When patients arrived outside
      working hours, the WT phase duration increased by 20 min (P < 0.001). When seen
      outside working hours, the ATT phase duration increased by 34.5 min (P < 0.001).
      CONCLUSION: Extrinsic to the patients themselves and in addition to ED
      overcrowding, the working hours of the hospital affected efficiency of care
      within the ED. Not only should the whole of the hospital be involved in improving
      efficient and safe transit of patients through an ED, but the whole of the day
      and every day of the week deserve attention.

PMID- 25370169
TI  - Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo.
AB  - Mitochondrial dysfunction has been reported in both familial and sporadic
      Parkinson's disease (PD). However, effective therapy targeting this pathway is
      currently inadequate. Recent studies suggest that manipulating the processes of
      mitochondrial fission and fusion has considerable potential for treating human
      diseases. To determine the therapeutic impact of targeting these pathways on PD,
      we used two complementary mouse models of mitochondrial impairments as seen in
      PD. We show here that blocking mitochondrial fission is neuroprotective in the
      PTEN-induced putative kinase-1 deletion (PINK1(-/-)) and 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine mouse models. Specifically, we show that inhibition of
      the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) using gene
      based and small-molecule approaches attenuates neurotoxicity and restores pre
      existing striatal dopamine release deficits in these animal models. These results
      suggest Drp1 inhibition as a potential treatment for PD. 

PMID- 25370172
TI  - Identifying barriers to smoking cessation in rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to investigate disease-related issues that
      make smoking cessation challenging for patients with rheumatoid arthritis (RA).
      There is currently a lack of research on tailoring smoking cessation
      interventions for RA patients. Qualitative exploration is a necessary first step
      in planning targeted interventions. METHODS: A qualitative mixed-methods study
      was undertaken. Participants attended either a focus group or an individual
      interview and completed a set of standardized questionnaires. The sample
      consisted of 36 RA patients: 24 current smokers and 12 ex-smokers. The
      transcripts were analyzed thematically using a critical realist approach to
      inductively identify themes. RESULTS: Five key barriers to smoking cessation that
      are faced by RA patients were identified. First, participants were unaware of the
      relationship between smoking and RA and therefore did not perceive this as a
      reason to quit. Second, smoking was used as a distraction from pain. Third,
      participants found it difficult to exercise and therefore were unable to use
      exercise as an alternative distraction. Fourth, smoking was used as a coping
      mechanism for the frustrations of living with RA. Fifth, participants felt
      unsupported and isolated from other RA patients. CONCLUSION: Disease-related
      issues may hinder smoking cessation for RA patients. Through an understanding of
      patients' perspectives there is an opportunity to plan an effective targeted
      intervention that may increase the chance of smoking cessation in RA patients
      where smoking may adversely influence disease progression and comorbidities.

PMID- 25370173
TI  - Femorotibial relationship changes as the posture changes from patellae-forward
      stance to preferred toe-out stance.
AB  - BACKGROUND: Full-length standing anteroposterior radiograph is a standard
      protocol to evaluate the lower limb alignment in frontal plane. However, most
      people tend to stand or walk with feet pointing outward. The purpose of this
      study is to assess the femorotibial relationship as the posture changes from
      patellae-forward stance for the conventional technique of a full-length standing
      anteroposterior radiograph to a toe-out quiet stance using a fluoroscope.
      METHODS: Femoral and tibial rotation and femorotibial rotation were measured in
      60 healthy lower limbs using fluoroscopy during postural change from patellae
      forward stance to toe-out quiet stance. RESULTS: The average toe-out angle was
      21.4 degrees . The average femoral, tibial, and femorotibial rotations during
      postural change were 6.1 degrees , 4.0 degrees , and 2.1 degrees , respectively
      (p = 0.000). The correlation coefficient for femoral and tibial rotation was
      0.747 (p = 0.000). The correlation coefficient for femoral and femorotibial
      rotation was 0.670 (p = 0.000), and for tibial and femorotibial rotation was
      0.006 (p = 0.962). The correlation between toe-out angle and femorotibial
      rotation was statistically significant (r (2) = 0.096, p = 0.016). The
      correlations between toe-out angle and femoral rotation, and between toe-out
      angle and tibial rotation were not statistically significant (r (2) = 0.047, p =
      0.095, and r (2) = 0.000, p = 0.9, respectively). CONCLUSIONS: The subject's
      posture significantly affects the femorotibial relationship. When a subject
      changes posture from a patellae-forward stance to a toe-out quiet stance, the
      femur rotates internally on the tibia. LEVEL OF EVIDENCE: Diagnostic, level II.

PMID- 25370175
TI  - Conservation implications of parasite co-reintroduction.

PMID- 25370174
TI  - Involvement of adiponectin in early stage of colorectal carcinogenesis.
AB  - BACKGROUND: Although altered levels of adiponectin have been reported as a
      potential risk factor in colorectal cancer (CRC), the importance of the role
      played by adiponectin in colorectal carcinogenesis has not been established. We
      sought to examine the expression pattern of adiponectin and adiponectin receptors
      (AdipoRs) in the normal-adenoma-carcinoma sequence and to assess the implications
      of adiponectin in colorectal carcinogenesis. METHODS: Serum adiponectin
      concentrations, and the mRNA and protein expression of adiponectin and AdipoRs
      were examined using serum and tissues from patients with CRC, advanced adenoma,
      and a normal colon. mRNA expression of AdipoRs and epithelial-mesenchymal
      transition regulators including E-cadherin, cyclooxygenase-2 (COX-2) and T
      cadherin were examined in HCT116 cells treated with adiponectin. RESULTS: Serum
      adiponectin concentrations in patients with advanced adenoma and CRC were lower
      than those in controls. Adiponectin mRNA was not detected in colonic tissue,
      whereas AdipoRs mRNA was lower in advanced adenoma and CRC than that in normal
      colon tissues. Immunohistochemical staining demonstrated that adiponectin was
      expressed in spindle-shaped cells of the subepithelial layer in normal colon
      tissues, whereas ill-defined overexpression of adiponectin was seen in the stroma
      of advanced adenoma and CRC tissues. AdipoRs expression was strong in normal
      epithelium, but weak to negative in the epithelia of CRC tissues. Adiponectin
      downregulated COX-2 mRNA expression in vitro, but upregulated T-cadherin in
      HCT116 cells. CONCLUSIONS: Systemic adiponectin and local AdipoRs expression in
      the colon may be associated with anti-tumorigenesis during the early stages of
      CRC. These findings offer new insight into understanding the relationship between
      adiponectin and colorectal carcinogenesis.

PMID- 25370176
TI  - [Therapy of inherited diseases of platelet function. Interdisciplinary S2K
      guideline of the Permanent Paediatric Committee of the Society of Thrombosis and
      Haemostasis Research (GTH e. V.)].
AB  - Inherited disorders of platelet function are a heterogeneous group. For optimal
      prevention and management of bleeding, classification and diagnosis of the
      underlying defect are highly recommended. An interdisciplinary guideline for a
      diagnostic approach has been published (AWMF # 086-003 S2K; Hamostaseologie 2014;
      34: 201-212). Underlying platelet disorder, platelet count, age and clinical
      situation modify treatment. Exclusive transfusion of platelet concentrates may be
      inappropriate as potentially adverse effects can outweigh its benefit. A stepwise
      and individually adjusted approach for restitution and maintenance of haemostasis
      is recommended. Administration of antifibrinolytics is generally endorsed, but is
      of particular use in Quebec disease. Restricted to older children, desmopressin
      is favourable in storage pool disease and unclassified platelet disorders.
      Although licensed only for patients with Glanzmann thrombasthenia and
      alloantibodies, in clinical practice rFVIIa is widely used in inherited platelet
      disorders with severe bleeding tendency. This guideline aims at presenting the
      best available advice for the management of patients with inherited platelet
      function disorders. 

PMID- 25370177
TI  - [Prophylactic factor substitution in severe haemophilia A. Economic assessment in
      adult patients].
AB  - Prophylaxis in adults can be necessary and reasonable for clinical reasons. The
      aim was to evaluate from an economic viewpoint prophylactic factor VIII
      substitution in adult patients with haemophilia in Germany. PATIENTS, METHODS: A
      decision model (time frame: one year; perspective: statutory health insurance;
      reference patient (RP) and 2 patient profiles) was developed. Calculations are
      based on data from a structured literature search and a pharmacovigilance study:
      therapy switch on-demand/prophylaxis (OD/Proph). RESULTS: RP: 45 years, 20 bleeds
      p.a. OD, 16 bleeds avoided with 8.5 I.U./kg/d Proph, additional cost Euro 141,113
      p.a.; profile 1: 50 years, 55 bleeds p.a. OD, factor consumption per bleed 20
      I.U./kg higher than RP, 39 bleeds avoided with 8.5 I.U./kg/d Proph, additional
      cost Euro 19,134 p.a.; profile 2: 60 years, 35 bleeds p.a. OD, factor consumption
      per bleed 40-80 I.U./kg higher than RP, 34 bleeds avoided with 11 I.U./kg/d
      Proph, cost reduction Euro 660 p.a. CONCLUSIONS: Prophylactic factor VIII
      substitution in adult haemophilia patients is depending on the individual
      clinical situation not only clinically but also economically reasonable. To
      evaluate this effects in the future comprehensively, longitudinal real-life data
      from patient-centered care are needed including clinical outcomes, quality of
      life and adherence.

PMID- 25370178
TI  - Relative kinetic expressions defining cleavage synchronicity are better
      predictors of blastocyst formation and quality than absolute time points.
AB  - PURPOSE: Morphology alone is not enough for the selection of the embryo (s) with
      the highest implantation potential and time-lapse imaging has added embryo
      development kinetics as another selection criterion. Therefore, a combination of
      morphology with kinetics has inspired a new field termed "morphokinetics",
      providing a new way of evaluating and selecting embryos. The aim of the study was
      to identify a criterion solely based on morphokinetic data and available up to
      the 8-cell stage (t8) to predict blastocyst formation and quality. METHODS: The
      study included 3,354 embryos, with annotations up to t8, and cultured until day 5
      from 626 infertile patients. A total of 17 kinetic expressions, either absolute
      cleavage timings and time intervals or time ratios were tested retrospectively
      for the prediction of blastocyst formation and quality. RESULTS: Relative timings
      (t8-t5, the cleavage synchronicity from 4 to 8 cells and from 2 to 8 cells) were
      found to be better indicators of blastocyst formation and quality when compared
      to absolute time-points. Especially, the cleavage synchronicity from 2 to 8 cells
      (CS2-8) = ((t3-t2) + (t5-t4))/(t8-t2)) was found to be the best predictor
      available on day 3 for blastocyst formation and quality (AUC:0.786; sensitivity:
      83.43; specificity: 62.46). CONCLUSIONS: Time intervals and relative ratios based
      on selected cleavage cycles defining synchronicity allowed a specific analysis
      providing high predictivity of blastocyst formation and quality.

PMID- 25370179
TI  - To what extent does Anti-Mullerian Hormone contribute to a better prediction of
      live birth after IVF?
AB  - OBJECTIVE: We assessed the predictive value added by Anti-Mullerian Hormone (AMH)
      to currently validated live birth (LB) prediction models. METHODS: Based on
      recent data from our center, we compared the external validity of the Templeton
      Model (TM) and its recent improvement (TMA) to select our model of reference. The
      added predictive value of AMH was assessed in testing the likelihood ratio
      significance and the Net Reclassification Index (NRI). The surrogate utility of
      AMH was tested by conducting an exploratory stepwise logistic regression.
      RESULTS: Based on 715 cycles, the original TM had poor performances (auROC C =
      0.61 [0.58, 0.66], improving by fitting TM to our data (C = 0.71[0.66, 0.75]. TMA
      fitting proved better (C = 0.76; 95 %CI: 0.71, 0.80) and was selected as model of
      reference. Adding AMH to TMA or TM had no effect on discrimination (C = 0.76; 95
      %CI: 0.72, 0.80), the likelihood ratio test was significant (p = 0.023), but the
      NRI was not (6.7 %; p = 0.055). A stepwise exploratory logistic regression
      identified the effects of age, previous IVF resulting in LB, time trend and AMH,
      leading to a prediction model reduced to four predictors (C = 0.75 [0.70, 0.81]).
      CONCLUSION: The added predictive value of AMH is limited. A possible
      surrogate/simplifying effect of AMH was found in eliminating 9/13 predictors from
      the model of reference. We conclude that whereas AMH does not add significant
      predictive value to the existing model, it contributes to simplifying the
      equation to reliable, easy to collect, and available in all databases predictors:
      age, AMH, time trend and female previous fertility history.

PMID- 25370180
TI  - Epab and Pabpc1 are differentially expressed in the postnatal mouse ovaries.
AB  - PURPOSE: Embryonic poly(A)-binding protein (EPAB) and poly(A)-binding protein,
      cytoplasmic 1 (PABPC1) bind poly(A) tails of mRNAs and mediate their
      translational regulation in germ cells and early preimplantation embryos.
      Although expression patterns and possible functions of the Epab and Pabpc1 genes
      have been examined in vertebrate germ cells and early embryos, their expression
      levels and cellular localizations in the postnatal mouse ovaries remained
      elusive. METHODS: In the present study, we first aimed to characterize expression
      levels of the Epab and Pabpc1 genes in the prepubertal (1-, 2-, and 3-week old),
      pubertal (4-, 5-, and 6-week old), postpubertal (16-week and 18-week old), and
      aged (52-, 60-, and 72-week old) mouse ovaries by using quantitative real-time
      polymerase chain reaction (qRT-PCR). RESULTS: Epab mRNA was predominantly
      expressed in the prepubertal ovaries when compared to later developmental
      periods. However, Pabpc1 transcript was highly generated in the prepubertal and
      pubertal mouse ovaries except for 1-week old ovary than those of other
      developmental terms. In the prepubertal mouse ovaries, RNA in situ hybridization
      localized both Epab and Pabpc1 transcripts in the cytoplasm of oocytes and
      granulosa cells of all follicular stages. Consistently, Epab and Pabpc1 gene
      expression were detected in the cumulus cells and MII oocytes obtained from
      cumulus oocyte complexes (COCs). Ovarian follicle counting in the postnatal
      ovaries revealed that total number of follicles was higher in the prepubertal
      ovaries in comparison with later stages of development. CONCLUSION: As a result,
      Epab and Pabpc1 expression exhibit differences at postnatal ovary development
      stages and both genes are transcribed in the granulosa cells and oocytes. These
      findings suggest that EPAB may predominantly play roles in translational
      regulation of the mRNAs during early oogenesis and folliculogenesis, but PABPC1
      most likely perform these roles in the later terms of ovarian development along
      with EPAB protein.

PMID- 25370181
TI  - Metabolomics study on model rats of chronic obstructive pulmonary disease treated
      with Bu-Fei Jian-Pi.
AB  - The therapeutic effect of Traditional Chinese Medicine (TCM) on chronic
      obstructive pulmonary disease (COPD) has been know for numerous years; however,
      the mechanism of action of the beneficial effects of TCM remains to be
      elucidated. The present study aimed to investigate the molecular mechanisms of
      COPD through metabolomic analysis as well as explore the targets and intervention
      mechanisms of TCM therapy using the common TCM granules Bu-Fei Jian-Pi. COPD rat
      models were established using smoke inhalations and recurrent bacterial
      infections. Rats were then divided into three groups as follows: A1, control
      healthy rats; B1, COPD model; and D1, Bu-Fei Jian-Pi-treated COPD rats. Following
      administration of the medicine, the metabolomic profile of the lung tissue of
      rats in each group was assessed using high-performance liquid
      chromatography/quadrupole-time-of-flight mass spectrometry. The results
      demonstrated that there was a significanlty different spectrum of metabolites in
      the lung tissue of the model group compared to that of the control group as well
      as the Bu-Fei Jian-Pi-treated COPD group; in addition, following treatment with
      Bu-Fei Jian-Pi, the metabolites of COPD rats were comparable with those of the
      control. Notable changes were observed in 31 metabolites between the Bu-Fei Jian
      Pi-treated group and the model group; however, there were 13 comparable
      metabolites between the Bu-Fei Jian-Pi and control groups as well as the model
      and control groups. Eleven metabolites showed a negative fold change in the Bu
      Fei Jian-Pi-treated groups compared to concentrations in the model group;
      however, minimal changes were observed in phenylpyruvic acid and alpha-D-fucose
      expression. In conclusion, the results of the present study demonstrated that Bu
      Fei Jian-Pi granules had beneficial effects on measured outcomes in a rat model
      of stable COPD, indicated by a significantly different spectrum of metabolites.
      This therefore indicated that the metabolites which had significantly altered
      expression in the model group compared with that of the control and Bu-Fei Jian
      Pi-treated groups may be potential biomarkers of COPD.

PMID- 25370182
TI  - Cucurbit[8]uril-based stimuli-responsive films as a sacrificial layer for
      preparation of free-standing thin films.
AB  - A pseudo-polycation was prepared based on the supramolecular cucurbit[8]uril
      ternary complex. It was then layer-by-layer assembled with poly(acrylic acid) to
      fabricate a stimuli-responsive film, which exhibited disassembly properties in
      response to stimuli, providing a supramolecular route for the fabrication of free
      standing thin films. 

PMID- 25370183
TI  - Recurrent pyoderma gangrenosum after cesarean delivery successfully treated with
      vacuum-assisted closure and split thickness skin graft: a case report.
AB  - We describe the case of a 32-year-old woman (gravidity: 4; parity: 2) who
      underwent cesarean delivery at 37 weeks of gestation and presented with
      dehiscence and infection of the surgical wound. She had a history of wound
      infection and dehiscence of the scar from a previous cesarean delivery and
      dehiscence in the dorsal side of her left hand at the site of intravenous
      catheterization. The patient was initially diagnosed with a skin infection and
      later with pyoderma gangrenosum. No evidence of any underlying disease was found.
      The lesions were treated with systemic corticosteroids and azathioprine, but the
      lesions were unresponsive to treatment. This complicated case of pyoderma
      gangrenosum after cesarean delivery, which initially mimicked wound infection,
      was successfully treated with vacuum-assisted closure and split-thickness skin
      graft. This synergistic approach with vacuum-assisted closure could be an
      important treatment option for aggressive and slow-healing lesions. 

PMID- 25370184
TI  - ESR spectroscopy as a powerful tool for probing the quality of conjugated
      polymers designed for photovoltaic applications.
AB  - Here we report the application of the Electron Spin Resonance (ESR) spectroscopy
      as a highly sensitive analytical technique for assessment of the electronic
      quality of organic semiconductor materials, particularly conjugated polymers. It
      has been shown that different batches of the same conjugated polymer might
      contain substantially different amounts of radical species which were attributed
      to structural defects and/or impurities behaving as traps for mobile charge
      carriers. Good correlations between the concentrations of radicals in various
      batches of conjugated polymers and their performances in organic solar cells have
      been revealed. 

PMID- 25370186
TI  - Novel method to predict body weight in children based on age and morphological
      facial features.
AB  - A new and novel approach of predicting the body weight of children based on age
      and morphological facial features using a three-layer feed-forward artificial
      neural network (ANN) model is reported. The model takes in four parameters,
      including age-based CDC-inferred median body weight and three facial feature
      distances measured from digital facial images. In this study, thirty-nine
      volunteer subjects with age ranging from 6-18 years old and BW ranging from 18.6
      96.4 kg were used for model development and validation. The final model has a
      mean prediction error of 0.48, a mean squared error of 18.43, and a coefficient
      of correlation of 0.94. The model shows significant improvement in prediction
      accuracy over several age-based body weight prediction methods. Combining with a
      facial recognition algorithm that can detect, extract and measure the facial
      features used in this study, mobile applications that incorporate this body
      weight prediction method may be developed for clinical investigations where
      access to scales is limited. 

PMID- 25370185
TI  - The addition of fluoxetine to cognitive behavioural therapy for youth depression
      (YoDA-C): study protocol for a randomised control trial.
AB  - BACKGROUND: The aim of the Youth Depression Alleviation-Combined Treatment (YoDA
      C) study is to determine whether antidepressant medication should be started as a
      first-line treatment for youth depression delivered concurrently with
      psychotherapy. Doubts about the use of medication have been raised by meta
      analyses in which the efficacy and safety of antidepressants in young people have
      been questioned, and subsequent treatment guidelines for youth depression have
      provided only qualified support. METHODS/DESIGN: YoDA-C is a double-blind,
      randomised controlled trial funded by the Australian government's National Health
      and Medical Research Council. Participants between the ages of 15 and 25 years
      with moderate to severe major depressive disorder will be randomised to receive
      either (1) cognitive behavioural therapy (CBT) and fluoxetine or (2) CBT and
      placebo. The treatment duration will be 12 weeks, and follow-up will be conducted
      at 26 weeks. The primary outcome measure is change in the Montgomery-Asberg
      Depression Rating Scale (MADRS) after 12 weeks of treatment. The MADRS will be
      administered at baseline and at weeks 4, 8, 12 and 26. Secondary outcome measures
      will address additional clinical outcomes, functioning, quality of life and
      safety. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ID: ACTRN12612001281886 (registered on 11 December 2012).

PMID- 25370187
TI  - Diabetes-independent increase of factor VII-activating protease activation in
      patients with Gram-negative sepsis (melioidosis).
AB  - BACKGROUND: The plasma protease factor VII-activating protease (FSAP) can release
      nucleosomes from late apoptotic cells. Nucleosomes are markers of cell death, and
      extracellular cell-free DNA has been suggested to play an important role in
      inflammation and has been demonstrated to correlate with severity and outcome in
      sepsis patients. OBJECTIVE: To investigate FSAP activation in patients suffering
      from Burkholderia pseudomallei infection (melioidosis), an important cause of
      Gram-negative sepsis in Southeast Asia. As diabetes mellitus (DM) is the most
      important risk factor for both melioidosis and sepsis, we were also able to
      examine the role of DM in FSAP activation in this cohort of patients. METHODS: In
      a prospective observational study, complexes of FSAP with alpha2 -antiplasmin
      (AP) were assayed in 44 patients with melioidosis, 34 of whom were classified as
      diabetic. Eighty-two healthy subjects served as controls (52 with DM and 30
      without). RESULTS: FSAP-AP complex levels were markedly elevated in patients as
      compared with controls. The FSAP level increased by 16.82 AU mL(-1) in patients
      with melioidosis after adjustment for the effect of DM in the regression model.
      As expected, FSAP activation was correlated with nucleosome release (slope =
      0.74). No difference in FSAP activation on admission was seen between survivors
      and non-survivors, but the extent of FSAP activation correlated with stage of the
      disease; repeated testing during convalescence showed a return towards normal
      values (day 0 vs. day 28, 4.16 AU mL(-1) , 95% confidence interval [CI] 1.42
      12.22). CONCLUSION: Patients with Gram-negative sepsis caused by B. pseudomallei
      have abundant FSAP activation, which significantly correlates with stage of
      disease. The presence of DM, however, does not influence the extent of FSAP
      activation.

PMID- 25370188
TI  - The Role of Mechanical Stimulation in Recovery of Bone Loss-High versus Low
      Magnitude and Frequency of Force.
AB  - Musculoskeletal pathologies associated with decreased bone mass, including
      osteoporosis and disuse-induced bone loss, affect millions of Americans annually.
      Microgravity-induced bone loss presents a similar concern for astronauts during
      space missions. Many pharmaceutical treatments have slowed osteoporosis, and
      recent data shows promise for countermeasures for bone loss observed in
      astronauts. Additionally, high magnitude and low frequency impact such as running
      has been recognized to increase bone and muscle mass under normal but not
      microgravity conditions. However, a low magnitude and high frequency (LMHF)
      mechanical load experienced in activities such as postural control, has also been
      shown to be anabolic to bone. While several clinical trials have demonstrated
      that LMHF mechanical loading normalizes bone loss in vivo, the target tissues and
      cells of the mechanical load and underlying mechanisms mediating the responses
      are unknown. In this review, we provide an overview of bone adaptation under a
      variety of loading profiles and the potential for a low magnitude loading as a
      way to counteract bone loss as experienced by astronauts. 

PMID- 25370189
TI  - RNA catalysis, thermodynamics and the origin of life.
AB  - The RNA World Hypothesis posits that the first self-replicating molecules were
      RNAs. RNA self-replicases are, in general, assumed to have employed nucleotide 5'
      polyphosphates (or their analogues) as substrates for RNA polymerization. The
      mechanism by which these substrates might be synthesized with sufficient
      abundance to supply a growing and evolving population of RNAs is problematic for
      evolutionary hypotheses because non-enzymatic synthesis and assembly of
      nucleotide 5'-triphosphates (or other analogously activated phosphodiester
      species) is inherently difficult. However, nucleotide 2',3'-cyclic phosphates are
      also phosphodiesters, and are the natural and abundant products of RNA
      degradation. These have previously been dismissed as viable substrates for
      prebiotic RNA synthesis. We propose that the arguments for their dismissal are
      based on a flawed assumption, and that nucleotide 2',3'-cyclic phosphates in fact
      possess several significant, advantageous properties that indeed make them
      particularly viable substrates for prebiotic RNA synthesis. An RNA World
      hypothesis based upon the polymerization of nucleotide 2',3'-cyclic phosphates
      possesses additional explanatory power in that it accounts for the observed
      ribozyme "fossil record", suggests a viable mechanism for substrate transport
      across lipid vesicle boundaries of primordial proto-cells, circumvents the
      problems of substrate scarcity and implausible synthetic pathways, provides for a
      primitive but effective RNA replicase editing mechanism, and definitively
      explains why RNA, rather than DNA, must have been the original catalyst. Finally,
      our analysis compels us to propose that a fundamental and universal property that
      drives the evolution of living systems, as well as pre-biotic replicating
      molecules (be they composed of RNA or protein), is that they exploit chemical
      reactions that already possess competing kinetically-preferred and
      thermodynamically-preferred pathways in a manner that optimizes the balance
      between the two types of pathways. 

PMID- 25370190
TI  - Disk evolution, element abundances and cloud properties of young gas giant
      planets.
AB  - We discuss the chemical pre-conditions for planet formation, in terms of gas and
      ice abundances in a protoplanetary disk, as function of time and position, and
      the resulting chemical composition and cloud properties in the atmosphere when
      young gas giant planets form, in particular discussing the effects of unusual,
      non-solar carbon and oxygen abundances. Large deviations between the abundances
      of the host star and its gas giants seem likely to occur if the planet formation
      follows the core-accretion scenario. These deviations stem from the separate
      evolution of gas and dust in the disk, where the dust forms the planet cores,
      followed by the final run-away accretion of the left-over gas. This gas will
      contain only traces of elements like C, N and O, because those elements have
      frozen out as ices. PRODIMO protoplanetary disk models are used to predict the
      chemical evolution of gas and ice in the midplane. We find that cosmic rays play
      a crucial role in slowly un-blocking the CO, where the liberated oxygen forms
      water, which then freezes out quickly. Therefore, the C/O ratio in the gas phase
      is found to gradually increase with time, in a region bracketed by the water and
      CO ice-lines. In this regions, C/O is found to approach unity after about 5 Myrs,
      scaling with the cosmic ray ionization rate assumed. We then explore how the
      atmospheric chemistry and cloud properties in young gas giants are affected when
      the non-solar C/O ratios predicted by the disk models are assumed. The DRIFT
      cloud formation model is applied to study the formation of atmospheric clouds
      under the influence of varying premordial element abundances and its feedback
      onto the local gas. We demonstrate that element depletion by cloud formation
      plays a crucial role in converting an oxygen-rich atmosphere gas into carbon-rich
      gas when non-solar, premordial element abundances are considered as suggested by
      disk models. 

PMID- 25370191
TI  - Cineradiographic analysis of mouse postural response to alteration of gravity and
      jerk (gravity deceleration rate).
AB  - The ability to maintain the body relative to the external environment is
      important for adaptation to altered gravity. However, the physiological limits
      for adaptation or the disruption of body orientation are not known. In this
      study, we analyzed postural changes in mice upon exposure to various low
      gravities. Male C57BL6/J mice (n = 6) were exposed to various gravity
      deceleration conditions by customized parabolic flight-maneuvers targeting the
      partial-gravity levels of 0.60, 0.30, 0.15 and MU g (<0.001 g). Video recordings
      of postural responses were analyzed frame-by-frame by high-definition
      cineradiography and with exact instantaneous values of gravity and jerk. As a
      result, the coordinated extension of the neck, spine and hindlimbs was observed
      during the initial phase of gravity deceleration. Joint angles widened to 120%
      200% of the reference g level, and the magnitude of the thoracic-curvature
      stretching was correlated with gravity and jerk, i.e., the gravity deceleration
      rate. A certain range of jerk facilitated mouse skeletal stretching efficiently,
      and a jerk of -0.3~-0.4 j (g/s) induced the maximum extension of the thoracic
      curvature. The postural response of animals to low gravity may undergo
      differential regulation by gravity and jerk. 

PMID- 25370192
TI  - Effects of the Extraterrestrial Environment on Plants: Recommendations for Future
      Space Experiments for the MELiSSA Higher Plant Compartment.
AB  - Due to logistical challenges, long-term human space exploration missions require
      a life support system capable of regenerating all the essentials for survival.
      Higher plants can be utilized to provide a continuous supply of fresh food,
      atmosphere revitalization, and clean water for humans. Plants can adapt to
      extreme environments on Earth, and model plants have been shown to grow and
      develop through a full life cycle in microgravity. However, more knowledge about
      the long term effects of the extraterrestrial environment on plant growth and
      development is necessary. The European Space Agency (ESA) has developed the Micro
      Ecological Life Support System Alternative (MELiSSA) program to develop a closed
      regenerative life support system, based on micro-organisms and higher plant
      processes, with continuous recycling of resources. In this context, a literature
      review to analyze the impact of the space environments on higher plants, with
      focus on gravity levels, magnetic fields and radiation, has been performed. This
      communication presents a roadmap giving directions for future scientific
      activities within space plant cultivation. The roadmap aims to identify the
      research activities required before higher plants can be included in regenerative
      life support systems in space. 

PMID- 25370194
TI  - Horizontal Gene Transfer among Bacteria and Its Role in Biological Evolution.
AB  - This is a contribution to the history of scientific advance in the past 70 years
      concerning the identification of genetic information, its molecular structure,
      the identification of its functions and the molecular mechanisms of its
      evolution. Particular attention is thereby given to horizontal gene transfer
      among microorganisms, as well as to biosafety considerations with regard to
      beneficial applications of acquired scientific knowledge. 

PMID- 25370193
TI  - Plant Growth and Morphogenesis under Different Gravity Conditions: Relevance to
      Plant Life in Space.
AB  - The growth and morphogenesis of plants are entirely dependent on the
      gravitational acceleration of earth. Under microgravity conditions in space,
      these processes are greatly modified. Recent space experiments, in combination
      with ground-based studies, have shown that elongation growth is stimulated and
      lateral expansion suppressed in various shoot organs and roots under microgravity
      conditions. Plant organs also show automorphogenesis in space, which consists of
      altered growth direction and spontaneous curvature in the dorsiventral (back and
      front) directions. Changes in cell wall properties are responsible for these
      modifications of growth and morphogenesis under microgravity conditions. Plants
      live in space with interesting new sizes and forms. 

PMID- 25370195
TI  - Opening up Peer Review in Life: Towards a Transparent and Reliable Process.
AB  - As an advocate of the transparency on the peer review process, during the last
      months, I've been working with MDPI to implant a new system of open peer review,
      under which the peer-review reports and authors' responses are published as an
      integral part of the final version of each article. This new model of publishing
      associated with the open access platform of MDPI result in one of the most
      transparent, unbiased, democratic and reliable assessment of research currently
      available. Life is the first MDPI journal to make this courageous step towards
      open peer-review in order to demonstrate the rigorous, fair and efficient
      standard of our editorial work. The first paper published under this new policy
      was a manuscript written by a Nobelist and reviewed by three experts in the
      field, as highlighted in this editorial. 

PMID- 25370196
TI  - The evolution of the ribosome and the genetic code.
AB  - The evolution of the genetic code is mapped out starting with the aminoacyl tRNA
      synthetases and their interaction with the operational code in the tRNA acceptor
      arm. Combining this operational code with a metric based on the biosynthesis of
      amino acids from the Citric acid, we come to the conclusion that the earliest
      genetic code was a Guanine Cytosine (GC) code. This has implications for the
      likely earliest positively charged amino acids. The progression from this pure GC
      code to the extant one is traced out in the evolution of the Large Ribosomal
      Subunit, LSU, and its proteins; in particular those associated with the Peptidyl
      Transfer Center (PTC) and the nascent peptide exit tunnel. This progression has
      implications for the earliest encoded peptides and their evolutionary progression
      into full complex proteins. 

PMID- 25370197
TI  - Host-microbe interactions in microgravity: assessment and implications.
AB  - Spaceflight imposes several unique stresses on biological life that together can
      have a profound impact on the homeostasis between eukaryotes and their associated
      microbes. One such stressor, microgravity, has been shown to alter host-microbe
      interactions at the genetic and physiological levels. Recent sequencing of the
      microbiomes associated with plants and animals have shown that these interactions
      are essential for maintaining host health through the regulation of several
      metabolic and immune responses. Disruptions to various environmental parameters
      or community characteristics may impact the resiliency of the microbiome, thus
      potentially driving host-microbe associations towards disease. In this review, we
      discuss our current understanding of host-microbe interactions in microgravity
      and assess the impact of this unique environmental stress on the normal
      physiological and genetic responses of both pathogenic and mutualistic
      associations. As humans move beyond our biosphere and undergo longer duration
      space flights, it will be essential to more fully understand microbial fitness in
      microgravity conditions in order to maintain a healthy homeostasis between
      humans, plants and their respective microbiomes. 

PMID- 25370198
TI  - Stem Cells toward the Future: The Space Challenge.
AB  - Astronauts experience weightlessness-induced bone loss due to an unbalanced
      process of bone remodeling that involves bone mesenchymal stem cells (bMSCs), as
      well as osteoblasts, osteocytes, and osteoclasts. The effects of microgravity on
      osteo-cells have been extensively studied, but it is only recently that
      consideration has been given to the role of bone MSCs. These live in adult bone
      marrow niches, are characterized by their self-renewal and multipotent
      differentiation capacities, and the published data indicate that they may lead to
      interesting returns in the biomedical/bioengineering fields. This review
      describes the published findings concerning bMSCs exposed to simulated/real
      microgravity, mainly concentrating on how mechanosignaling, mechanotransduction
      and oxygen influence their proliferation, senescence and differentiation. A
      comprehensive understanding of bMSC behavior in microgravity and their role in
      preventing bone loss will be essential for entering the future age of long
      lasting, manned space exploration. 

PMID- 25370199
TI  - Chemically and biologically harmless versus harmful ferritin/copper
      metallothionein couples.
AB  - The simultaneous measurement of the decrease of available Fe(II) ions and the
      increase of available Fe(III) ions allowed the analysis of the ferroxidase
      activity of two distinct apoferritins. Although recombinant human apoferritin
      (HuFtH) rapidly oxidizes Fe(II) to Fe(III) , this iron is not properly stored in
      the ferritin cavity, as otherwise occurs in horse-spleen H/L-apoferritin (HsFt;
      H=heavy subunit, L=light subunit). Iron storage in these apoferritins was also
      studied in the presence of two copper-loaded mammalian metallothioneins (MT2 and
      MT3), a scenario that occurs in different brain-cell types. For HuFtH, unstored
      Fe(III) ions trigger the oxidation of Cu-MT2 with concomitant Cu(I) release. In
      contrast, there is no reaction with Cu-MT2 in the case of HsFt. Similarly, Cu-MT3
      does not react during either HuFtH or HsFt iron reconstitution. Significantly,
      the combination of ferritin and metallothionein isoforms reported in glia and
      neuronal cells are precisely those combinations that avoid a harmful release of
      Fe(II) and Cu(I) ions. 

PMID- 25370200
TI  - Keeping silent about emergency contraceptives in Addis Ababa: a qualitative study
      among young people, service providers, and key stakeholders.
AB  - BACKGROUND: The growing popularity of emergency contraceptives (ECs) among urban
      youth in Sub-Saharan Africa is accompanied by debates on morality and health.
      This study was situated in Addis Ababa, Ethiopia and aimed to explore how these
      debates affect the way in which the product is promoted at a national level, how
      it is dispensed by service providers, and how young people access, purchase, and
      get informed about ECs. METHODS: Data were collected using qualitative methods:
      observations in pharmacies, administering semi-structured questionnaires to young
      people in pharmacies (N = 36), informal interviews with young people (N = 65),
      and in-depth interviews with service providers (N = 8) and key stakeholders (N =
      3). RESULTS: Key stakeholders, uncomfortable with high sales of ECs, and service
      providers, worried about women's health, promiscuity and the neglect of condoms,
      stay silent about ECs. Most young people had used ECs more than once. In a
      context where premarital sex is morally sanctioned ECs provide young people with
      a way of keeping their sexual lives secret and they fit well with their sex lives
      that often entail infrequent sexual encounters. Young people preferred (but they
      are also left with no other option than) to seek information from discreet
      sources, including friends and partners, leaflets and the mass media. In
      addition, service providers misunderstood young people's purchasing behaviour,
      characterized by buying ECs quickly and feeling too embarrassed to ask questions,
      as a rejection of counselling. The resultant lack of information about ECs
      sometimes led to confusion about how to take the pills. CONCLUSIONS: The
      attitudes and beliefs of key stakeholders and service providers result in a lack
      of clear information on ECs available to young people. This could be addressed by
      improving the information leaflet, providing clear instructions of use on blister
      packages, strategically distributing posters, and service providers adopting a
      more proactive attitude.

PMID- 25370202
TI  - GJB1-associated X-linked Charcot-Marie-Tooth disease, a disorder affecting the
      central and peripheral nervous systems.
AB  - Charcot-Marie-Tooth disease (CMT) is a group of inherited diseases characterized
      by exclusive or predominant involvement of the peripheral nervous system.
      Mutations in GJB1, the gene encoding Connexin 32 (Cx32), a gap-junction channel
      forming protein, cause the most common X-linked form of CMT, CMT1X. Cx32 is
      expressed in Schwann cells and oligodendrocytes, the myelinating glia of the
      peripheral and central nervous systems, respectively. Thus, patients with CMT1X
      have both central and peripheral nervous system manifestations. Study of the
      genetics of CMT1X and the phenotypes of patients with this disorder suggest that
      the peripheral manifestations of CMT1X are likely to be due to loss of function,
      while in the CNS gain of function may contribute. Mice with targeted ablation of
      Gjb1 develop a peripheral neuropathy similar to that seen in patients with CMT1X,
      supporting loss of function as a mechanism for the peripheral manifestations of
      this disorder. Possible roles for Cx32 include the establishment of a reflexive
      gap junction pathway in the peripheral and central nervous system and of a
      panglial syncitium in the central nervous system. 

PMID- 25370203
TI  - WITHDRAWN:Radix astragali induces in vitro and in vivo synthesis of fetal
      hemoglobin in non-transfusion-dependent beta-thalassemia: A preliminary study.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 25370201
TI  - Systematic review and proposal of a field-based physical fitness-test battery in
      preschool children: the PREFIT battery.
AB  - BACKGROUND: Physical fitness is a powerful health marker in childhood and
      adolescence, and it is reasonable to think that it might be just as important in
      younger children, i.e. preschoolers. At the moment, researchers, clinicians and
      sport practitioners do not have enough information about which fitness tests are
      more reliable, valid and informative from the health point of view to be
      implemented in preschool children. OBJECTIVE: Our aim was to systematically
      review the studies conducted in preschool children using field-based fitness
      tests, and examine their (1) reliability, (2) validity, and (3) relationship with
      health outcomes. Our ultimate goal was to propose a field-based physical fitness
      test battery to be used in preschool children. DATA SOURCES: PubMed and Web of
      Science. STUDY ELIGIBILITY CRITERIA: Studies conducted in healthy preschool
      children that included field-based fitness tests. STUDY APPRAISAL AND SYNTHESIS
      METHODS: When using PubMed, we included Medical Subject Heading (MeSH) terms to
      enhance the power of the search. A set of fitness-related terms were combined
      with 'child, preschool' [MeSH]. The same strategy and terms were used for Web of
      Science (except for the MeSH option). Since no previous reviews with a similar
      aim were identified, we searched for all articles published up to 1 April 2014
      (no starting date). A total of 2,109 articles were identified, of which 22
      articles were finally selected for this review. RESULTS: Most studies focused on
      reliability of the fitness tests (n = 21, 96%), while very few focused on
      validity (0 criterion-related validity and 4 (18%) convergent validity) or
      relationship with health outcomes (0 longitudinal and 1 (5%) cross-sectional
      study). Motor fitness, particularly balance, was the most studied fitness
      component, while cardiorespiratory fitness was the least studied. After analyzing
      the information retrieved in the current systematic review about fitness testing
      in preschool children, we propose the PREFIT battery, field-based FITness testing
      in PREschool children. The PREFIT battery is composed of the following tests: the
      20 m shuttle-run test for assessing cardiorespiratory fitness, the handgrip
      strength and the standing long-jump tests for assessing musculoskeletal fitness,
      and the 4 * 10 m shuttle run and the one-leg-stance tests for assessing motor
      fitness, i.e. speed/agility and balance, respectively. The rationale for the
      selection of each of the tests included in the PREFIT battery is provided in this
      review, as well as directions for future research. LIMITATIONS: Levels of
      evidence based on quality assessment of selected studies could not be constructed
      due to the limited number of studies identified for each test. CONCLUSIONS: The
      present systematic review has identified a need for further research on the
      validity of fitness tests in preschool children, as well as on their relationship
      with health. Due to this limited information, the PREFIT battery hereby proposed
      is based on the output of the current systematic review in preschool children,
      together with existing evidence in older children and adolescents. While we wait
      for more evidence to be accumulated in preschool children, the PREFIT battery
      hereby proposed is a useful tool for assessing physical fitness in children aged
      3-5 years.

PMID- 25370204
TI  - Associations of chronic heart failure with outcome in acute ischaemic stroke
      patients who received systemic thrombolysis: analysis from VISTA.
AB  - BACKGROUND AND PURPOSE: There are concerns that systemic thrombolysis might not
      achieve clinically important outcome amongst chronic heart failure (CHF) patients
      with acute ischaemic stroke. Our aim was to investigate the relevance of CHF on
      the outcome of acute stroke patients who received thrombolysis. METHODS: A non
      randomized cohort analysis was conducted using data obtained from the Virtual
      International Stroke Trials Archive. The association of outcome amongst CHF
      patients with thrombolysis treatment was described using the modified Rankin
      scale (mRS) distribution at day 90, stratified by the presence of atrial
      fibrillation. Dichotomized outcomes were considered as a secondary end-point.
      RESULTS: 5677 patients were identified, of whom 2366 (41.7%) received
      thombolysis. Five hundred and three (8.9%) patients had CHF, of whom 209 (41.6%)
      received thrombolysis. The presence of CHF was associated with a negative impact
      on overall stroke outcome [odds ratio (OR) 0.73 (95% confidence interval (CI)
      0.62-0.87), P < 0.001]. However, thrombolysis treatment was associated with
      favourable functional outcome using ordinal mRS, irrespective of CHF status,
      after adjustment for age and baseline National Institutes of Health Stroke Scale
      [OR 1.44 (95% CI 1.04-2.01, P = 0.029) for CHF patients versus OR 1.50 (95% CI
      1.36-1.66, P < 0.001) for non-CHF patients]. CHF patients had higher mortality at
      day 90 than non-CHF patients. There was no significant difference for recurrent
      stroke or symptomatic intracerebral haemorrhage within 7 days of the initial
      stroke between CHF and thrombolysis groups. CONCLUSIONS: Chronic heart failure
      was associated with a worse outcome with or without thrombolysis. However, acute
      stroke patients who received thrombolysis had more favourable outcome regardless
      of CHF status, compared with their untreated peers. Our findings should reassure
      clinicians considering systemic thrombolysis treatment in hyperacute ischaemic
      stroke patients with CHF.

PMID- 25370205
TI  - Evaluation of young men with organic erectile dysfunction.
AB  - Erectile dysfunction (ED) in men under the age of 40 was once thought to be
      entirely psychogenic. Over the last few decades, advances in our understanding of
      erectile physiology and improvements in diagnostic testing have restructured our
      understanding of ED and its etiologies. Although psychogenic ED is more prevalent
      in the younger population, at least 15%-20% of these men have an organic
      etiology. Organic ED has been shown to be a predictor of increased future
      morbidity and mortality. As such, a thorough work-up should be employed for any
      man with complaints of sexual dysfunction. Oftentimes a treatment plan can be
      formulated after a focused history, physical exam and basic lab-work are
      conducted. However, in certain complex cases, more testing can be employed. The
      major organic etiologies can be subdivided into vascular, neurologic, and
      endocrine. Specific testing should be directed by clinical clues noted during the
      preliminary evaluation. These tests vary in degree of invasiveness, precision,
      and at times may not affect treatment. Results should be integrated into the
      overall clinical picture to assist in diagnosis and help guide therapy. 

PMID- 25370206
TI  - An open-label, multicenter, randomized, crossover study comparing sildenafil
      citrate and tadalafil for treating erectile dysfunction in Chinese men naive to
      phosphodiesterase 5 inhibitor therapy.
AB  - The study was to compare treatment preference, efficacy, and tolerability of
      sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction
      (ED) in Chinese men naomicronve to phosphodiesterase 5 (PDE5) inhibitor
      therapies. This multicenter, randomized, open-label, crossover study evaluated
      whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After
      a 4 weeks baseline assessment, 383 eligible patients were randomized to
      sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks
      respectively and then chose which treatment they preferred to take during the 8
      weeks extension. Primary efficacy was measured by Question 1 of the PDE5
      Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was
      analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF)
      erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3,
      and the Drug Attributes Questionnaire. Three hundred and fifty men (91%)
      completed the randomized treatment phase. Two hundred and forty-two per 350
      (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg
      sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two
      per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly
      the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse),
      and IIEF-EF domain scores were improved in both tadalafil and sildenafil
      treatment groups. For patients who preferred tadalafil, getting an erection long
      after taking the medication was the most reported reason for tadalafil
      preference. The only treatment-emergent adverse event reported by > 2% of men was
      headache. After tadalafil and sildenafil treatments, more Chinese men with ED
      naomicronve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil
      treatments were effective and safe. 

PMID- 25370208
TI  - Effect of Smad3/4 on chemotherapeutic drug sensitivity in colorectal cancer
      cells.
AB  - Smad3 and Smad4 are signaling mediators in the transforming growth factor beta
      (TGFbeta) pathway and play a major role in the progression and migration of many
      types of cancers. The TGFbeta pathway is correlated with resistance against both
      targeted and conventional chemotherapeutic drugs. The aim of this study was to
      determine the effect of Smad3/4 on drug sensitivity in chemotherapy-resistant
      colorectal cancer (CRC) cells. We isolated the TGFbeta-mediated chemoresistant
      CRC cell line DLD1-5FU-C10, which showed high expression of Smad3/4 and p21. In
      order to analyze the influence of Smad3/4 on drug sensitivity in DLD1-5FU-C10
      cells, we knocked down Smad3/4 using small interfering RNAs (siRNA). The results
      showed similar drug sensitivity between the DLD1-5FU-C10 and the DLD1 control
      cells and reduced p21 expression. In addition, we found a significant increase in
      the levels of 3 TGFbeta downstream factors: interleukin 6 (IL6), plasminogen
      activator (PLAU) and prostaglandin-endoperoxide synthase 2 (PTGS2). Furthermore,
      we showed that Smad3/4 regulated the JAK1/STAT3 pathway via IL6 in the
      chemoresistant CRC cell line. In conclusion, we identified Smad3/4 as a novel
      drug sensitivity regulator in TGFbeta-mediated chemotherapy-resistant CRC cells.
      Our results suggest that Smad3/4 regulate p-STAT3 signaling by IL6 and p21 and
      highlight an important role for STAT3 signaling in Smad3/4 regulated drug
      sensitivity in chemoresistant CRC cells.

PMID- 25370207
TI  - Anatase titanium dioxide nanoparticles in mice: evidence for induced structural
      and functional sperm defects after short-, but not long-, term exposure.
AB  - Titanium dioxide (TiO 2 ) nanoparticles (TNPs) are widely used commercially and
      exist in a variety of products. To determine if anatase TNPs (ATNPs) in doses
      smaller than previously used reach the scrotum after entry in the body at a
      distant location and induce sperm defects, 100% ATNP (2.5 or 5 mg kg-1 body
      weight) was administered intraperitoneally to adult males for three consecutive
      days, followed by sacrifice 1, 2, 3, or 5 weeks later (long-) or 24, 48 or 120 h
      (short-term exposure). Transmission electron microscopy revealed the presence of
      ANTP in scrotal adipose tissues collected 120 h postinjection when cytokine
      evaluation showed an inflammatory response in epididymal tissues and fluid. At
      120 h and up to 3 weeks postinjection, testicular histology revealed enlarged
      interstitial spaces. Significantly increased numbers of terminal
      deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling-positive
      (apoptotic) germ (P = 0.002) and interstitial space cells (P = 0.04) were
      detected in treated males. Caudal epididymal sperm from the short-term, but not a
      long-term, arm showed significantly (P < 0.001) increased frequencies of
      flagellar abnormalities, excess residual cytoplasm (ERC), and unreacted acrosomes
      in treated versus controls (dose-response relationship). A novel correlation
      between ERC and unreacted acrosomes was uncovered. At 120 h, there were
      significant decreases in hyperactivated motility (P < 0.001) and mitochondrial
      membrane potential (P < 0.05), and increased reactive oxygen species levels (P <
      0.00001) in treated versus control sperm. These results indicate that at 4-8 days
      postinjection, ANTP induce structural and functional sperm defects associated
      with infertility, and DNA damage via oxidative stress. Sperm defects were
      transient as they were not detected 10 days to 5 weeks postinjection. 

PMID- 25370209
TI  - Influence of crosslinking on the wear performance of polyethylene within total
      ankle arthroplasty.
AB  - BACKGROUND: Wear debris of polyethylene within joint replacement systems can
      result in clinical complications including osteolysis and component loosening.
      Highly crosslinked polyethylene (HXPE) was introduced to improve these outcomes,
      and has been shown to result in improved wear performance in several joint
      replacement systems. However, bearing couples within total ankle replacement
      (TAR) systems have historically used conventional polyethylene (CPE) articulating
      on metal. The extent to which HXPE would result in a reduction of polyethylene
      wear compared to CPE in the ankle has not been studied. The hypothesis motivating
      this study was that use of HXPE within TAR will result in significantly lower
      wear rate than CPE. METHODS: HXPE and CPE inserts within a semiconstrained,
      bicondylar TAR system were manufactured for this study. Samples were subjected to
      5.0 million cycles of wear on an in vitro wear simulator. Testing was performed
      within a physiological environment, using kinematic and kinetic loading profiles
      characteristic of walking gait. Samples were weighed at regular intervals to
      determine gravimetric mass loss, and the morphology of wear particles was
      analyzed. RESULTS: The wear rates for CPE and HXPE samples were 7.4 +/- 1.3 and
      1.9 +/- 0.3 mg/Mc (mean +/- SD), respectively. HXPE samples exhibited a
      significant (P < .01) wear rate reduction of 74% when compared with the CPE.
      Debris morphology trends between HXPE and CPE were consistent with what has been
      observed in other joint systems. CONCLUSION: Use of HXPE significantly reduces
      wear of TAR as compared to CPE, based on in vitro wear testing. CLINICAL
      RELEVANCE: Highly crosslinked polyethylene may reduce clinical complications of
      total ankle replacement that are linked to polyethylene wear.

PMID- 25370210
TI  - A maximum-likelihood estimation of pairwise relatedness for autopolyploids.
AB  - Relatedness between individuals is central to ecological genetics. Multiple
      methods are available to quantify relatedness from molecular data, including
      method-of-moment and maximum-likelihood estimators. We describe a maximum
      likelihood estimator for autopolyploids, and quantify its statistical performance
      under a range of biologically relevant conditions. The statistical performances
      of five additional polyploid estimators of relatedness were also quantified under
      identical conditions. When comparing truncated estimators, the maximum-likelihood
      estimator exhibited lower root mean square error under some conditions and was
      more biased for non-relatives, especially when the number of alleles per loci was
      low. However, even under these conditions, this bias was reduced to be
      statistically insignificant with more robust genetic sampling. We also considered
      ambiguity in polyploid heterozygote genotyping and developed a weighting
      methodology for candidate genotypes. The statistical performances of three
      polyploid estimators under both ideal and actual conditions (including inbreeding
      and double reduction) were compared. The software package POLYRELATEDNESS is
      available to perform this estimation and supports a maximum ploidy of eight. 

PMID- 25370211
TI  - Origin and genome evolution of polyploid green toads in Central Asia: evidence
      from microsatellite markers.
AB  - Polyploidization, which is expected to trigger major genomic reorganizations,
      occurs much less commonly in animals than in plants, possibly because of
      constraints imposed by sex-determination systems. We investigated the origins and
      consequences of allopolyploidization in Palearctic green toads (Bufo viridis
      subgroup) from Central Asia, with three ploidy levels and different modes of
      genome transmission (sexual versus clonal), to (i) establish a topology for the
      reticulate phylogeny in a species-rich radiation involving several closely
      related lineages and (ii) explore processes of genomic reorganization that may
      follow polyploidization. Sibship analyses based on 30 cross-amplifying
      microsatellite markers substantiated the maternal origins and revealed the
      paternal origins and relationships of subgenomes in allopolyploids. Analyses of
      the synteny of linkage groups identified three markers affected by translocation
      events, which occurred only within the paternally inherited subgenomes of
      allopolyploid toads and exclusively affected the linkage group that determines
      sex in several diploid species of the green toad radiation. Recombination rates
      did not differ between diploid and polyploid toad species, and were overall much
      reduced in males, independent of linkage group and ploidy levels. Clonally
      transmitted subgenomes in allotriploid toads provided support for strong genetic
      drift, presumably resulting from recombination arrest. The Palearctic green toad
      radiation seems to offer unique opportunities to investigate the consequences of
      polyploidization and clonal transmission on the dynamics of genomes in
      vertebrates. 

PMID- 25370212
TI  - Patterns of chromosomal variation in natural populations of the neoallotetraploid
      Tragopogon mirus (Asteraceae).
AB  - Cytological studies have shown many newly formed allopolyploids
      (neoallopolyploids) exhibit chromosomal variation as a result of meiotic
      irregularities, but few naturally occurring neoallopolyploids have been examined.
      Little is known about how long chromosomal variation may persist and how it might
      influence the establishment and evolution of allopolyploids in nature. In this
      study we assess chromosomal composition in a natural neoallotetraploid,
      Tragopogon mirus, and compare it with T. miscellus, which is an allotetraploid of
      similar age (~40 generations old). We also assess whether parental gene losses in
      T. mirus correlate with entire or partial chromosome losses. Of 37 T. mirus
      individuals that were karyotyped, 23 (62%) were chromosomally additive of the
      parents, whereas the remaining 14 individuals (38%) had aneuploid compositions.
      The proportion of additive versus aneuploid individuals differed from that found
      previously in T. miscellus, in which aneuploidy was more common (69%; Fisher's
      exact test, P=0.0033). Deviations from parental chromosome additivity within T.
      mirus individuals also did not reach the levels observed in T. miscellus, but
      similar compensated changes were observed. The loss of T. dubius-derived genes in
      two T. mirus individuals did not correlate with any chromosomal changes,
      indicating a role for smaller-scale genetic alterations. Overall, these data for
      T. mirus provide a second example of prolonged chromosomal instability in natural
      neoallopolyploid populations. 

PMID- 25370213
TI  - Hallauer's Tuson: a decade of selection for tropical-to-temperate phenological
      adaptation in maize.
AB  - Crop species exhibit an astounding capacity for environmental adaptation, but
      genetic bottlenecks resulting from intense selection for adaptation and
      productivity can lead to a genetically vulnerable crop. Improving the genetic
      resiliency of temperate maize depends upon the use of tropical germplasm, which
      harbors a rich source of natural allelic diversity. Here, the adaptation process
      was studied in a tropical maize population subjected to 10 recurrent generations
      of directional selection for early flowering in a single temperate environment in
      Iowa, USA. We evaluated the response to this selection across a geographical
      range spanning from 43.05 degrees  (WI) to 18.00 degrees  (PR) latitude. The
      capacity for an all-tropical maize population to become adapted to a temperate
      environment was revealed in a marked fashion: on average, families from
      generation 10 flowered 20 days earlier than families in generation 0, with a nine
      day separation between the latest generation 10 family and the earliest
      generation 0 family. Results suggest that adaptation was primarily due to
      selection on genetic main effects tailored to temperature-dependent plasticity in
      flowering time. Genotype-by-environment interactions represented a relatively
      small component of the phenotypic variation in flowering time, but were
      sufficient to produce a signature of localized adaptation that radiated
      latitudinally, in partial association with daylength and temperature, from the
      original location of selection. Furthermore, the original population exhibited a
      maladaptive syndrome including excessive ear and plant heights along with later
      flowering; this was reduced in frequency by selection for flowering time. 

PMID- 25370214
TI  - Teaching dermatoscopy of pigmented skin tumours to novices: comparison of
      analytic vs. heuristic approach.
AB  - BACKGROUND: There are two strategies to approach the dermatoscopic diagnosis of
      pigmented skin tumours, namely the verbal-based analytic and the more visual
      global heuristic method. It is not known if one or the other is more efficient in
      teaching dermatoscopy. OBJECTIVE: To compare two teaching methods in short-term
      training of dermatoscopy to medical students. METHODS: Fifty-seven medical
      students in the last year of the curriculum were given a 1-h lecture of either
      the heuristic- or the analytic-based teaching of dermatoscopy. Before and after
      this session, they were shown the same 50 lesions and asked to diagnose them and
      rate for chance of malignancy. Test lesions consisted of melanomas, basal cell
      carcinomas, nevi, seborrhoeic keratoses, benign vascular tumours and
      dermatofibromas. Performance measures were diagnostic accuracy regarding
      malignancy as measured by the area under the curves of receiver operating curves
      (range: 0-1), as well as per cent correct diagnoses (range: 0-100%). RESULTS:
      Diagnostic accuracy as well as per cent correct diagnoses increased by +0.21 and
      +32.9% (heuristic teaching) and +0.19 and +35.7% (analytic teaching) respectively
      (P for all <0.001). Neither for diagnostic accuracy (P = 0.585), nor for per cent
      correct diagnoses (P = 0.298) was a difference between the two groups.
      CONCLUSIONS: Short-term training of dermatoscopy to medical students allows
      significant improvement in diagnostic abilities. Choosing a heuristic or analytic
      method does not have an influence on this effect in short training using common
      pigmented skin lesions.

PMID- 25370216
TI  - Our troops and veterans deserve first-class care.
AB  - Hundreds of nurses gave their lives during the 20th century's two world wars, and
      many more have risked everything to provide care at or close to the front line in
      other conflicts. Most recently, nursing staff have provided invaluable support to
      our troops in Afghanistan, a mission that has now come to an end. 

PMID- 25370215
TI  - A study on the mechanical characteristics of the EBM-printed Ti-6Al-4V LCP plates
      in vitro.
AB  - PURPOSE: The electron beam melting (EBM) Ti-6Al-4V material technology has been
      developed over a short time period. It was introduced through a research to
      develop Ti-6Al-4V implants for patients, but EBM printed locking compression
      plates have not been used for clinical implants. The main purpose of this study
      is to find whether the EBM Ti-6Al-4V plate suit for clinical implants. METHODS:
      First, we scanned an AO-locking compression plate (LCP) and printed LCP samples
      using EBM. Next, we evaluated the EBM plate surface roughness through optical
      microscopy as well as the LCP and EBM plates' mechanical characteristics using
      the ASTM standard, which is commonly used to test the mechanical properties of
      bone plates subject to bending. Each sample was examined using a single-cycle
      four-point bending test and hardness testing to acquire data on bending
      stiffness, bending strength, bending structural stiffness, and hardness. RESULTS:
      The results show significant differences in bending stiffness, bending strength,
      bending structural stiffness, and hardness between the samples using EBM and the
      original LCP plates. The EBM-printed samples' surface roughness was 0.49 +/- 0.02
      MUm. The mean hardness of the LCP sample was 266.67 HV10 +/- 5.8, and the EBM
      printed sample mean hardness was 341.1 HV10 +/- 1.93. The EBM samples' bending
      stiffness was 87.67%, which is greater than using the LCP plates'; and the
      bending strength was 190.7% greater, the bending structural stiffness was 73.2%
      greater, and the hardness was 27.9% greater. CONCLUSIONS: The results show that
      the EBM plates' general mechanical strength was significantly greater than the
      LCP plates. An EBM plate is advantageous for clinical implants because it can be
      customized with great potential for improvement.

PMID- 25370217
TI  - Hundreds of hospitals in England fail to reach safe staffing levels.
AB  - More than half of England's hospitals are failing to meet their own safe staffing
      targets for nurses, according to a national patient safety website.

PMID- 25370218
TI  - Regulators to encourage a more transparent health service.
AB  - Nurses and midwives have a duty to be open and honest with patients and own up to
      mistakes, according to new draft guidance from the Nursing and Midwifery Council.

PMID- 25370219
TI  - Supply of nurses 'is like relying on payday loans'.
AB  - The number of nurses coming to work in the UK from overseas has shot up by 45 per
      cent in a year, research by the RCN has revealed.

PMID- 25370220
TI  - Most staff at care homes would back having cameras in residents' rooms.
AB  - Six out of ten staff in one of the UK's largest care home providers have said
      they would welcome CCTV cameras in residents' rooms to root out poor care. 

PMID- 25370221
TI  - RCN asks public to sign its petition for safe staffing.
AB  - RCN Wales is urging members of the public to sign an e-petition supporting draft
      legislation on safer staffing. 

PMID- 25370222
TI  - Second pay strike set to be bigger as further action adds to pressure.
AB  - Thousands of nurses and midwives in England are preparing to strike for the
      second time in six weeks in protest at the government's refusal to give all NHS
      staff a 1 per cent cost of living pay rise.

PMID- 25370223
TI  - Midwives in Guernsey suspended amid conduct concerns.
AB  - Four senior midwives in Guernsey have been suspended from practising by their
      local supervising authority following complaints about their conduct.

PMID- 25370224
TI  - False alarms give hospital staff practice in managing Ebola care.
AB  - Most London hospitals have dealt with at least one patent with suspected Ebola
      virus in the past month, a leading infection control nurse has claimed. 

PMID- 25370225
TI  - Young carers take their message to the top of the NHS.
AB  - Teenage carers met nurses, doctors, political and NHS leaders at London Zoo to
      highlight the health and social care needs of an estimated 166,000 young carers
      in England. 

PMID- 25370228
TI  - Nurse-led cancer clinic saves money and pleases patients.
AB  - A nurse-led prostate cancer clinic that has saved money for its trust has been
      extended following positive feedback from patients. 

PMID- 25370227
TI  - Computer glitch is a 'blow to morale'.
AB  - Delays and spiralling costs of an IT upgrade for Scotland's NHS 24 helpline is a
      blow to nursing staff, the RCN says. 

PMID- 25370231
TI  - Poor communication causing hundreds of unsafe discharges.
AB  - Concerns about dangerous failings in how patients are discharged from hospital
      have been raised by a healthcare watchdog.

PMID- 25370232
TI  - MPs call for boost in mental health resources to meet military's needs.
AB  - Greater investment is urgently needed to support the growing number of serving
      military personnel and veterans experiencing mental health problems, an
      influential group of MPs said.

PMID- 25370234
TI  - Night-shift staff are more likely to struggle to remain a healthy weight.
AB  - Exhausted as the end of your night shift approaches, your eyes stinging with
      tiredness and limbs aching, the quick energy boost offered by a fizzy drink or
      bar of chocolate is tempting. 

PMID- 25370240
TI  - Antibiotic resistance.

PMID- 25370241
TI  - My grandmother and a nursing hero.

PMID- 25370242
TI  - ADHD assessment tool unlocks the truth.

PMID- 25370243
TI  - Championing the child health cause.

PMID- 25370258
TI  - 'Use us or lose us,' say the RCN's retired accredited representatives.
AB  - Debate is continuing over using the knowledge and skills of retired RCN
      representatives (Reflections October 8, Letters October 15 and 29). 

PMID- 25370259
TI  - Wearing gloves means that we lose out on skin-to-skin contact.

PMID- 25370261
TI  - Support the Welsh members' bill on safe nurse staffing levels.

PMID- 25370262
TI  - Helping a Polish nurse frustrated by delays in her NMC registration.

PMID- 25370263
TI  - With NMC delays, the best way to respond is to make a complaint.

PMID- 25370265
TI  - We do not need managers to tell us where the problems lie.

PMID- 25370266
TI  - Improving staff selection processes.
AB  - This article, the second in a series of articles on Leading Better Care,
      describes the actions undertaken in recent years in NHS Lanarkshire to improve
      selection processes for nursing, midwifery and allied health professional (NMAHP)
      posts. This is an area of significant interest to these professions, management
      colleagues and patients given the pivotal importance of NMAHPs to patient care
      and experience. In recent times the importance of selecting staff not only with
      the right qualifications but also with the right attributes has been highlighted
      to ensure patients are well cared for in a safe, effective and compassionate
      manner. The article focuses on NMAHP selection processes, tracking local,
      collaborative development work undertaken to date. It presents an overview of
      some of the work being implemented, highlights a range of important factors,
      outlines how evaluation is progressing and concludes by recommending further
      empirical research.

PMID- 25370267
TI  - The role of effective communication in achieving informed consent for clinical
      trials.
AB  - Informed consent is fundamental to the protection of the rights, safety and
      wellbeing of patients in clinical research. For consent to be valid, patients
      must first be given all the information they need about the proposed research to
      be able to decide whether they would like to take part. This material should be
      presented in a way that is easy for them to understand. This article explores the
      importance of communication in clinical research, and how more effective
      communication with patients during the informed consent process can ensure they
      are fully informed. 

PMID- 25370268
TI  - Economic evaluation of interventions in health care.
AB  - Economic evaluation is rapidly becoming an invaluable tool for healthcare
      decision making, especially in light of current pressures on health services to
      reduce costs and increase expenditure on health care. This article provides an
      overview of the main methods used for the economic evaluation of healthcare
      interventions, and their applications and limitations. It is intended as an
      introduction to the topic for readers with no background in economics, and can be
      used to review the basic concepts of economic evaluation in healthcare provision.

PMID- 25370269
TI  - Ascites.
AB  - I have looked after patients with ascites and those who have had large-volume
      paracentesis. This article has increased my understanding of ascites and helped
      to improve my nursing care. 

PMID- 25370270
TI  - Get ready to impress.
AB  - More than 40 trusts, charities, agencies and companies will be looking for the
      brightest recruits at the RCN Bulletin jobs fair in Leeds next month. Here are
      some top tips to ensure you make the right impression and give a winning
      performance to potential employers on the day. 

PMID- 25370272
TI  - A century on, their legacy remains.
AB  - The first world war both delayed the campaign for nursing regulation and
      reinforced the need for it. 

PMID- 25370274
TI  - Student life--When two worlds connect.
AB  - The light bulb moment came to me on a train when I met two people living with
      long-term conditions. It dawned on me that our nursing students could be an
      amazing resource to connect people who are socially isolated--older people, young
      people, carers and others--to beautiful spaces.

PMID- 25370276
TI  - Ionic liquid based approach for single-molecule electronics with cobalt contacts.
AB  - An electrochemical method is presented for fabricating cobalt thin films for
      single-molecule electrical transport measurements. These films are electroplated
      in an aqueous electrolyte, but the crucial stages of electrochemical reduction to
      remove surface oxide and adsorption of alkane(di)thiol target molecules under
      electrochemical control to form self-assembled monolayers which protect the oxide
      free cobalt surface are carried out in an ionic liquid. This approach yields
      monolayers on Co that are of comparable quality to those formed on Au by standard
      self-assembly protocols, as assessed by electrochemical methods and surface
      infrared spectroscopy. Using an adapted scanning tunneling microscopy (STM)
      method, we have determined the single-molecule conductance of cobalt/1,8
      octanedithiol/cobalt junctions by employing a monolayer on cobalt and a cobalt
      STM tip in an ionic liquid environment and have compared the results with those
      of experiments using gold electrodes as a control. These cobalt substrates could
      therefore have future application in organic spintronic devices such as magnetic
      tunnel junctions. 

PMID- 25370277
TI  - Depression and cancer.
AB  - Depression in patients with cancer can present a challenging clinical problem for
      both general practitioners and the oncology team. Detecting depression in a
      patient with cancer, who may be debilitated and in pain, can be difficult. Cancer
      treatments can complicate antidepressant choices. Community-based psychologists
      are an important resource for helping manage less complex and less severe
      psychological problems that can arise in the cancer setting. Specialist psycho
      oncology services (where available) can help with more complex and severe
      presentations of depression by advising on the prescription of antidepressants
      and providing psychotherapy programs that address the patient's psychological
      orientation and needs and consider the patient's cancer type and stage. 

PMID- 25370278
TI  - Depression and chronic pain.
AB  - Chronic pain and major depression commonly occur together. Major depression in
      patients with chronic pain is associated with decreased function, poorer
      treatment response and increased health care costs. The experience and expression
      of chronic pain vary between individuals, reflecting complex and changing
      interactions between physical, psychological and social processes. The diagnosis
      of major depression in patients with chronic pain requires differentiation
      between the symptoms of pain and symptoms of physical illness. Antidepressants
      and psychological therapies can be effective and should be delivered as part of a
      coordinated, cohesive, multidisciplinary pain management plan. 

PMID- 25370279
TI  - Depression, diet and exercise.
AB  - Unhealthy lifestyle behaviour is driving an increase in the burden of chronic non
      communicable diseases worldwide. Recent evidence suggests that poor diet and a
      lack of exercise contribute to the genesis and course of depression. While
      studies examining dietary improvement as a treatment strategy in depression are
      lacking, epidemiological evidence clearly points to diet quality being of
      importance to the risk of depression. Exercise has been shown to be an effective
      treatment strategy for depression, but this is not reflected in treatment
      guidelines, and increased physical activity is not routinely encouraged when
      managing depression in clinical practice. Recommendations regarding dietary
      improvement, increases in physical activity and smoking cessation should be
      routinely given to patients with depression. Specialised and detailed advice may
      not be necessary. Recommendations should focus on following national guidelines
      for healthy eating and physical activity. 

PMID- 25370275
TI  - An epigenetic switch induced by Shh signalling regulates gene activation during
      development and medulloblastoma growth.
AB  - The Sonic hedgehog (Shh) signalling pathway plays important roles during
      development and in cancer. Here we report a Shh-induced epigenetic switch that
      cooperates with Gli to control transcription outcomes. Before induction, poised
      Shh target genes are marked by a bivalent chromatin domain containing a
      repressive histone H3K27me3 mark and an active H3K4me3 mark. Shh activation
      induces a local switch of epigenetic cofactors from the H3K27 methyltransferase
      polycomb repressive complex 2 (PRC2) to an H3K27me3 demethylase Jmjd3/Kdm6b
      centred coactivator complex. We also find that non-enzymatic activities of Jmjd3
      are important and that Jmjd3 recruits the Set1/MLL H3K4 methyltransferase
      complexes in a Shh-dependent manner to resolve the bivalent domain. In vivo,
      changes of the bivalent domain accompanied Shh-activated cerebellar progenitor
      proliferation. Overall, our results reveal a regulatory mechanism that underlies
      the activation of Shh target genes and provides insight into the causes of
      various diseases and cancers exhibiting altered Shh signalling. 

PMID- 25370280
TI  - Depression and borderline personality disorder.
AB  - Borderline personality disorder (BPD) is a serious mental illness characterised
      by dysregulation of emotions and impulses, an unstable sense of self, and
      difficulties in interpersonal relationships, often accompanied by suicidal and
      self-harming behaviour. Major depressive disorder (MDD) commonly co-occurs with
      BPD. Patients with BPD often present with depressive symptoms. It can be
      difficult to distinguish between BPD and MDD, especially when the two disorders
      co-occur. Research is needed to clarify the commonalities and differences between
      BPD and MDD, and BPD and rapid-cycling bipolar disorder. When MDD and BPD co
      occur, both conditions should be treated concurrently. MDD co-occurring with BPD
      does not respond as well to antidepressant medication as MDD in the absence of
      BPD. MDD is not a significant predictor of outcome for BPD, but BPD is a
      significant predictor of outcome for MDD. Treatment of BPD with specific
      psychotherapies tends to result in remission of co-occurring MDD. Empirically
      validated psychotherapies for BPD share common features that are applicable in
      all treatment settings where patients with BPD are likely to present, including
      primary care. Methodologically sound research is required to examine the
      effectiveness of medications for treatment of MDD co-occurring with BPD. 

PMID- 25370281
TI  - Depression and anxiety.
AB  - Comorbid depression and anxiety disorders occur in up to 25% of general practice
      patients. About 85% of patients with depression have significant anxiety, and 90%
      of patients with anxiety disorder have depression. Symptomatology may initially
      seem vague and non-specific. A careful history and examination with relevant
      investigations should be used to make the diagnosis. Once the diagnosis is made,
      rating scales may identify illness severity and help in monitoring treatment
      progress. Both the depression disorder and the specific anxiety disorder require
      appropriate treatment. Psychological therapies, such as cognitive behaviour
      therapy, and antidepressants, occasionally augmented with antipsychotics, have
      proven benefit for treating both depression and anxiety. Benzodiazepines may help
      alleviate insomnia and anxiety but not depression. They have dependency and
      withdrawal issues for some people, and may increase the risk of falls in older
      people. Despite the availability of treatments, 40% of patients with depression
      or anxiety do not seek treatment, and of those who do, less than half are offered
      beneficial treatment. 

PMID- 25370282
TI  - Depression: an insider's view.

PMID- 25370283
TI  - Treatment of bipolar depression.
AB  - Depression is usually the predominant phase in bipolar disorder, causes the most
      psychosocial disability, and carries significant risk of suicide. The management
      of bipolar depression is relatively under-studied and poses significant
      challenges for clinicians. There is substantial dissent regarding optimal
      pharmacotherapy for bipolar depression, particularly around the role of
      antidepressants. Individual and combination pharmacotherapy should be integrated
      into a personalised psychosocial and lifestyle package of interventions that
      considers the person's clinical profile and preferences. The relative lack of
      evidence relating to optimal strategies, especially when bipolar depression
      occurs with common comorbidities, poses challenges and requires further research.
      A flexible approach and evidence-based combinations of treatments can provide
      effective strategies for improving quality of life and reducing morbidity and
      mortality. 

PMID- 25370284
TI  - Schizophrenia and depression.
AB  - Depressive symptoms are common in people with schizophrenia and can be associated
      with suicidality, but are often either missed or dismissed by clinicians. General
      practitioners have a key role in initial assessment and subsequent monitoring of
      depressive symptoms, associated risks and physical health in patients with
      schizophrenia. Liaison with appropriate non-government organisations and public
      or private specialist mental health services can enhance GPs' management of
      depression in schizophrenia. Antidepressants, prescribed in tandem with
      antipsychotics, have a likely therapeutic role for persistent depressive symptoms
      in schizophrenia, but side effects can be troublesome. Although some of the
      atypical antipsychotics appear to have primary antidepressant effects, the
      utility of these agents alone in the setting of persistent depressive symptoms in
      schizophrenia has not been established. 

PMID- 25370285
TI  - Difficult-to-treat depression.

PMID- 25370286
TI  - Depression and dementia.
AB  - Depression in people with dementia is a common presentation in primary care, but
      it is often missed or mismanaged. This problem has substantial public health
      implications and adversely affects the quality of life and physical health of
      patients and carers. Many aspects of diagnosis and management remain
      controversial. A high degree of suspicion and repeated assessment is essential
      for diagnosis. Medication use should be considered. Psychological and social
      strategies should be incorporated into most management plans. 

PMID- 25370287
TI  - Pharmacological treatment approaches to difficult-to-treat depression.
AB  - In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial of
      almost 3000 patients with depression in the United States, 50% responded to the
      initial trial of a selective serotonin reuptake inhibitor antidepressant, but
      only a third achieved remission (nil or minimal depressive symptoms). The final
      remission rate, even after four potential treatment steps, was only 70%. This
      finding reflects the reality of clinical practice and highlights the need to
      employ the best available evidence in the management of people with complex
      depression. Before adopting a pharmacological strategy for a patient with
      difficult-to-treat depression, general clinical issues (such as missed
      psychiatric diagnoses, unresolved psychological issues and treatment non
      adherence) should be considered. While there is no strong evidence for the order
      of implementing evidence-based pharmacological strategies for difficult-to-treat
      depression, we recommend: i) increase antidepressant dose; ii) switch to
      different antidepressant; iii) augment with a non-antidepressant agent; and iv)
      combine antidepressants. Sometimes it may be more appropriate to consider
      augmentation before switching antidepressants. The use of psychological
      interventions or other physical treatments such as electroconvulsive therapy
      should be considered at each step in management.

PMID- 25370288
TI  - Non-pharmacological biological treatment approaches to difficult-to-treat
      depression.
AB  - There has been substantial recent interest in novel brain stimulation treatments
      for difficult-to-treat depression. Electroconvulsive therapy (ECT) is a well
      established, effective treatment for severe depression. ECT's problematic side
      effect profile and questions regarding optimal administration methods continue to
      be investigated. Magnetic seizure therapy, although very early in development,
      shows promise, with potentially similar efficacy to ECT but fewer side effects.
      Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation
      (rTMS) are clinically available in some countries. Limited research suggests VNS
      has potentially long-lasting antidepressant effects in a small group of patients.
      Considerable research supports the efficacy of rTMS. Both techniques require
      further study of optimal treatment parameters. Transcranial direct current
      stimulation may provide a low-cost antidepressant option if its efficacy is
      substantiated in larger samples. Deep brain stimulation is likely to remain
      reserved for patients with the most severe and difficult-to-treat depression,
      requiring further exploration of administration methods and its role in
      depression therapy. New and innovative forms of brain stimulation, including low
      intensity ultrasound, low-field magnetic stimulation and epidural stimulation of
      the cortical surface, are in early stages of exploration and are yet to move into
      the clinical domain. Ongoing work is required to define which brain stimulation
      treatments are likely to be most useful, and in which patient groups. Clinical
      service development of brain stimulation treatments will likely be inconsistent
      and variable. 

PMID- 25370289
TI  - Psychosocial treatment approaches to difficult-to-treat depression.
AB  - Coexisting psychiatric and medical conditions, environmental and contextual
      factors, inadequate diagnosis and treatment, medication non-adherence, and issues
      such as low self-esteem, hopelessness and cognitive reactivity, can play a role
      in difficult-to-treat depression. A reduction in symptoms due to pharmacological
      treatment does not equate with full recovery, and some level of rehabilitation is
      often required. The evidence base for psychosocial therapies in difficult-to
      treat depression is small, with the research heavily weighted toward biological
      treatments. Nevertheless, combining psychological treatments with pharmacotherapy
      is likely to improve rates of recovery in difficult-to-treat depression.
      Psychological therapies can be useful in modifying health beliefs, treating
      comorbid anxiety and other disorders, dealing with contextual factors, and
      activating patients to facilitate their recovery. Effective treatment requires a
      multidisciplinary team involving a general practitioner and psychologist, and
      sometimes a psychiatrist. Effective communication and active engagement of
      patients and families is essential. 

PMID- 25370290
TI  - Difficult-to-treat-depression: what do general practitioners think?
AB  - OBJECTIVE: To understand the perspectives of a group of general practitioners
      regarding management of patients with difficult-to-treat depression (DTTD).
      DESIGN, SETTING AND PARTICIPANTS: A qualitative approach using a focus group and
      semi-structured telephone interviews conducted in 2011 with 10 GPs from urban and
      rural Victoria. Five main topics were explored: (1) understanding of DTTD; (2)
      understanding of other terms used to describe DTTD; (3) experiences of diagnosing
      DTTD; (4) experiences of managing DTTD; and (5) management options. RESULTS: The
      participants had generally poor recognition of diagnostic terms, and questioned
      their relevance. Participants felt that management guidelines were not always
      helpful. Access to psychiatrists was often difficult, and non-pharmacological or
      complementary treatments were considered to have a role in management.
      Environmental and cultural factors, social isolation and cost of treatment have
      an impact on patient adherence, and the participants felt that the professional
      patient relationship is important in ensuring comprehensive care. CONCLUSIONS:
      Despite extensive experience and knowledge of their patients, there were gaps in
      GPs' appraisal of the literature and about specific resources available. The GPs
      had little interest in the nuances of classifications; instead, their focus was
      on their patient and what to do in practical terms regarding optimal management.

PMID- 25370291
TI  - Depression and physical illness.
AB  - Depressive symptoms frequently accompany physical illness, but the association
      between the two is complex. The combination has detrimental implications for the
      patient's health outcome, quality of life, medical treatment and health care use.
      The presence of physical symptoms of the medical illness can lead to challenges
      in recognising and diagnosing depression. This is best dealt with by placing
      greater emphasis on the psychological symptoms of depression. Recognition may be
      improved through use of appropriate screening tools for depression in medically
      ill patients. The management of depression in the setting of medical illness
      involves both general and specific approaches. General approaches include optimal
      treatment of the medical illness, exclusion of treatments that are associated
      with depressive symptoms, and simple general health strategies aimed at improving
      sleep and exercise. Good evidence exists for selective psychotherapeutic
      approaches and antidepressant treatments, but care is required to avoid drug-drug
      and illness-drug interactions with the latter. 

PMID- 25370292
TI  - The Hindlimb Arterial Vessels in Lowland paca (Cuniculus paca, Linnaeus 1766).
AB  - This study aims to describe the origin and distribution of the hindlimb arterial
      vessels. Five adult lowland pacas (Cuniculus paca) were used. Stained and diluted
      latex was injected, caudally to the aorta. After fixation in 10% paraformaldehyde
      for 72 h, we dissected to visualize and identify the vessels. It was found out
      that the vascularization of the hindlimb in lowland paca derives from the
      terminal branch of the abdominal aorta. The common iliac artery divides into
      external iliac and internal iliac. The external iliac artery emits the deep iliac
      circumflex artery, the pudendal epigastric trunk, the deep femoral artery; the
      femoral artery originates the saphenous artery, it bifurcates into cranial and
      caudal saphenous arteries. Immediately after the knee joint, the femoral artery
      is called popliteal artery, which divides into tibial cranial and tibial caudal
      arteries at the level of the crural inter-osseous space. The origin and
      distribution of arteries in the hindlimb of lowland paca resembles that in other
      wild rodents, as well as in the domestic mammals.

PMID- 25370293
TI  - Frailty status can predict further lean body mass decline in older adults.
AB  - OBJECTIVES: To assess whether frailty is a risk factor for skeletal muscle mass
      decline in community-dwelling elderly people. DESIGN: Prospective observational
      cohort study. SETTING: Seongnam, Gyeongi Province, Korea. PARTICIPANTS: Community
      dwelling Koreans aged 65 and older (n = 341). MEASUREMENTS: Bioimpedance analysis
      (BIA) was used to measure body composition at baseline and 5 years later.
      Laboratory examination and comprehensive geriatric assessment were performed at
      both times. Lean mass index (LMI) was defined as total body lean mass/height(2).
      A decrease of more than 5% in the LMI was considered to be significant. Frailty
      status was defined using the Cardiovascular Health Study criteria. RESULTS: LMI
      decline occurred in 196 (54.1%) subjects during the follow-up period (5.0 +/- 0.7
      years). Baseline LMI was highest in robust (17.6 +/- 1.8 kg/m(2), n = 126), lower
      prefrail (17.0 +/- 1.7 kg/m(2), n = 185), and lowest in frail (16.7 +/- 1.3
      kg/m(2), n = 30) subjects (P < .001). Frailty status was associated with LMI
      decline at 5-year follow-up (robust 0.81 +/- 0.78 kg/m(2), prefrail 1.00 +/- 0.92
      kg/m(2), frail 1.35 +/- 0.85 kg/m(2), P < .001). This effect of frailty on LMI
      decline persisted after adjusting for covariables (P = .02). The risk of
      significant LMI decline was 2.9 times as great in frail elderly adults as in
      those who were robust even after adjusting for covariates (95% confidence
      interval = 1.01-8.55). CONCLUSION: Frailty status was found to be independently
      associated with subsequent LMI decline in community-dwelling older adults.

PMID- 25370294
TI  - Controlled trials of vitamin D, causality and type 2 statistical error.
AB  - Two recent studies published in The Lancet (Autier et al. (2013) Lancet Diabetes
      Endocrinol 2, 76-89 and Bolland et al. (2014) Lancet Diabetes Endocrinol 2, 307
      320) have concluded that low levels of vitamin D are not a cause but a
      consequence of ill health brought about by reduced exposure to the sun, an
      association known as 'reverse causality'. The scientific evidence and reasoning
      for these conclusions are examined here and found to be faulty. A null result in
      a clinical trial of vitamin D in adults need not lead to a conclusion of reverse
      causation when low vitamin D is found in observational studies of the same
      disease earlier in life. To assume an explanation of reverse causality has close
      similarities with type 2 statistical error. For example, a null result in
      providing vitamin D for treatment of adult bones that are deformed in the pattern
      of the rachitic rosary would not alter the observation that lack of vitamin D can
      cause rickets in childhood and may have lasting consequences if not cured with
      vitamin D. Other examples of diseases considered on a lifetime basis from
      conception to adulthood are used to further illustrate the issue, which is
      evidently not obvious and is far from trivial. It is concluded that deficiency of
      vitamin D in cohort studies, especially at critical times such as pregnancy and
      early life, can be the cause of a number of important diseases. Denial of the
      possible benefits of vitamin D, as suggested by insistent interpretation of
      studies with reverse causation, may lead to serious harms, some of which are
      listed. 

PMID- 25370296
TI  - Meta-analytic comparison between PIB-PET and FDG-PET results in Alzheimer's
      disease and MCI.
AB  - We conducted a meta-analysis of positron emission tomography (PET) findings in
      Alzheimer's disease (AD) and mild cognitive impairment (MCI) to clarify the
      changes underpinning these conditions. All studies that utilised the PET tracers
      Pittsburgh Compound-B (PIB) or 2-[18F]fluoro-2-deoxy-D-glucose (FDG) to
      investigate patients with MCI or AD, were considered for the meta-analysis. Meta
      analyses of PIB-PET and FDG-PET changes between patients and controls were
      undertaken with the effect-size signed differential mapping (ES-SDM) voxel-based
      meta-analytic method. A total of 24 studies were included involving 728 AD
      patients, 211 MCI patients and 658 healthy controls. Individuals with AD showed a
      significant PIB retention in bilateral precuneus and temporal, supramarginal,
      cingulate and fusiform gyri, as well as right insula and putamen. In addition, AD
      patients showed significant glucose hypometabolism in bilateral precuneus and
      temporal, supramarginal, cingulate, fusiform, angular, inferior parietal and
      middle frontal gyri, as well as left precentral and parahippocampal gyri and
      right superior frontal gyrus and thalamus. An exploratory meta-analysis of the
      few studies on MCI showed mildly decreased glucose metabolism with a similar
      regional distribution than in patients with AD. We suggest that our results can
      be used for further region-of-interest studies of AD and MCI patients. 

PMID- 25370295
TI  - Passive transfer of antibodies to the linear epitope 60 kD Ro 273-289 induces
      features of Sjogren's syndrome in naive mice.
AB  - Sjogren's syndrome (SS) is an autoimmune inflammatory disease that primarily
      affects the lacrimal and salivary glands causing dry eyes and mouth. Antibodies
      to Ro60 are observed frequently in patients with SS; however, the role of these
      antibodies in SS initiation and progression remains unclear. The sequence Ro60
      273-289 (Ro274) is a known B cell epitope of Ro60 and antibodies to this epitope
      have been observed in a subset of SS patients and in animals immunized with Ro60
      protein. Animals immunized with Ro274 linear peptide develop a Sjogren's-like
      illness. We hypothesized that passive transfer of anti-Ro274-specific
      immunoglobulin (Ig)G would induce a Sjogren's-like phenotype. To evaluate this
      hypothesis, we adoptively transferred affinity-purified Ro274 antibodies into
      naive BALB/c animals, then evaluated salivary gland histology, function and IgG
      localization 4 days post-transfer. At this time-point, there was no demonstrable
      mononuclear cell infiltration and salivary glands were histologically normal, but
      we observed a functional deficit in stimulated salivary flow of animals receiving
      Ro274 antibodies compared to animals receiving control IgG. Cellular
      fractionation and enzyme-linked immunosorbent assay revealed Ro274-specific
      antibodies in the nucleus and cytoplasmic fractions of isolated parotid salivary
      gland cells that was confirmed by immunohistochemistry. These data support the
      hypothesis that antibodies to Ro274 deposit in salivary glands can enter intact
      salivary gland cells and are involved in the dysregulation of salivary flow in
      SS. 

PMID- 25370297
TI  - Accelerated regeneration of skin injury by co-transplantation of mesenchymal stem
      cells from Wharton's jelly of the human umbilical cord mixed with microparticles.
AB  - This study was set to explore a new strategy for repairing skin wounds, co
      transplantation of mesenchymal stem cells from Wharton's Jelly of the human
      umbilical cord (hUC-Wharton's jelly-MSCs) and microparticles. A mixture of hUC
      Wharton's jelly-MSCs and microparticles was co-transplanted to 10-mm diameter,
      full-thickness, mid-dorsal, excisional skin wounds of mice. After 7, 14, and 21
      days, the tissue sections were sampled for reconstruction analysis and
      histological examination. Our results showed that hUC-Wharton's jelly-MSCs
      possess the potentials for multi-directional differentiation. After co
      transplantation, there was remarkable development of newborn skin and its
      appendages. Newly generated layers of epidermis, sebaceous glands, hair follicle,
      and sweat glands were observed. This promising innovative strategy could
      significantly increase the quality of repair and regeneration of skin after
      injuries. 

PMID- 25370298
TI  - Predictive validity of the Bayley, Third Edition at 2 years for intelligence
      quotient at 4 years in preterm infants.
AB  - OBJECTIVE: To determine the predictive validity of the Bayley Scales of Infant
      and Toddler Development, Third Edition (Bayley-III) at age 2 years for cognitive
      abilities in preschool children born at <= 30 weeks' gestation. METHODS: This
      prospective regional study included all 187 liveborn infants <= 30 weeks'
      gestation born between July 2005 and June 2006. Of the 172 children who survived
      to 4 years, 156 (91%) were evaluated at 2 and 4 years. A socioeconomically
      matched term control group also was recruited to provide normative data. The
      predictive validity of the Bayley-III cognitive and language scales for the
      Weschler Preschool and Primary Scale of Intelligence-III (WPPSI-III) was examined
      through correlation coefficients and sensitivity and specificity of the Bayley
      III to predict normal and abnormal cognitive outcomes. RESULTS: Correlations of
      the WPPSI-III intelligence quotient (IQ) score with the Bayley-III cognitive and
      language scores were .81 and .78, respectively. The preterm children were
      classified as normal (Bayley Scales of Infant Development-Third Edition [BSID
      III] cognitive score or WPPSI-III IQ score not lower than 1 SD below the control
      group mean), mild to moderately delayed (scores between 1 and 2 SD deviations
      below the control group mean), or severely delayed (scores greater than 2 SD
      below the control group mean). At 2 and 4 years, 126 (81%) preterm children
      retained the same developmental classification. CONCLUSIONS: In contrast with
      previous editions of the BSID, the Bayley-III has strong predictive validity for
      WPPSI-III IQ at age 4 years in preterm children. This has important implications
      for more timely evaluation of perinatal interventions, establishment of
      guidelines for neonatal care, and counseling parents.

PMID- 25370299
TI  - Regional disparities in psychiatric distress, violent behavior, and life
      satisfaction in Iranian adolescents: the CASPIAN-III study.
AB  - OBJECTIVES: The purpose of this study was to assess the prevalence of violence
      behaviors, psychiatric distress, and life satisfaction among 10- to 18-year-old
      Iranian adolescents at national and regional disparities. METHODS: In this
      national survey, 5570 students of age 10 to 18 years from urban and rural regions
      of 27 provinces of Iran were selected through stratified multistage sampling
      method. Violence behaviors, psychiatric distress, and life satisfaction were
      assessed by a questionnaire that was prepared based on WHO global school-based
      student health survey and the WHO-stepwise approach to noncommunicable diseases
      (Tools version 9.5). The country classification into 4 subnational regions was
      done based on combination of geography and socioeconomic status (SES). The data
      were analyzed by the SPSS software. RESULTS: The prevalence of emotional,
      depressive, and anxiety problem among Iranian students was 17.7%, 16.3%, and
      5.7%, respectively. The percentage of emotional and depressive problem differed
      significantly between different SES distress (p value <.001). The prevalence of
      bullying, victim, and physical fight was 27.1%, 32.7%, and 50.6% among students
      aged 10 to 18 years, respectively. Bullying and victim experience were linearly
      associated with regions' SES. Students who were living in the north-northeast
      region had maximum self-rated health and life satisfaction in Iran. CONCLUSIONS:
      The results declared that psychiatric distress was more frequent in high SES
      distress, whereas violence behavior was more frequent in the lowest SES distress.
      Therefore, in communities with large variations in health and SES in regional
      level, health policies for primordial and primary prevention of mental and
      behavioral distress have to be made at regional levels.

PMID- 25370300
TI  - Venous hemangioma of the anterior mediastinum.
AB  - Mediastinal hemangiomas are rare tumors, with an incidence of 0.5% or less. We
      herein present a case of venous hemangioma in the anterior mediastinum. A 61-year
      old man was admitted to our hospital complaining of dyspnea. Computed tomography
      scan of the thorax showed a 2.5 * 3.2 * 2 cm mass in the anterior mediastinum.
      Using a median sternotomy approach, the tumor was completely removed.
      Pathological examination confirmed a venous hemangioma. 

PMID- 25370301
TI  - Immunophenotype and human papillomavirus status of serous adenocarcinoma of the
      uterine cervix.
AB  - Serous adenocarcinoma of the cervix (SACC) is a very rare tumor. Our study aimed
      to characterize the immune profile and human papillomavirus (HPV) status of SACC,
      in comparison with other serous adenocarcinomas arising in the female genital
      tract. The pathological specimens obtained from 81 patients with serous carcinoma
      of the uterine cervix (n = 12), 29 endometrium, 20 ovary and 20 patients with
      mucinous carcinoma of the uterine cervix were reviewed. We assessed the
      expression of WT-1, p53, p16, HER2, CEA, and CA125 by immunohistochemistry and
      HPV DNA by PCR in 12 SACC samples. Their immune profile was compared with that of
      uterine papillary serous carcinoma (UPSC), ovarian serous adenocarcinoma (OSA),
      and mucinous endocervical adenocarcinoma (MEA). WT-1 and HER2 were expressed in
      very few SACC samples (0 and 0%, respectively), but p16, CA125, CEA and p53 were
      present in 100, 92, 58 and 50%, respectively. The difference in WT-1 expression
      between SACC and UPSC, MEA is not significant, but SACC differ significantly from
      OSA (p < 0.01). HPV DNA (type 16 or 18) was detected in 4 of the 12 SACC. The
      immunophenotype of SACC was similar to UPSC, whereas the frequency of expression
      of WT-1 was significantly lower in SACC than OSA. It appeared that p53 expression
      was associated with worse clinical outcome in patients with SACC, and that HPV
      infection was related to its occurrence.

PMID- 25370303
TI  - Copper-catalyzed regioselective synthesis of furan via tandem cycloaddition of
      ketone with an unsaturated carboxylic acid under air.
AB  - A catalytic decarboxylative annulation has been developed for the regioselective
      synthesis of trisubstituted furans by the cycloaddition of ketones with
      alpha,beta-unsaturated carboxylic acids under ambient air. A library of furan
      derivatives were obtained in good yields from the readily available substrates in
      the combination of a catalytic amount of Cu-salt and a stoichiometric amount of
      water. Water plays a crucial role in this catalytic transformation. 

PMID- 25370304
TI  - Advanced biorefinery based on the fractionation of biomass in gamma-valerolactone
      and water.
AB  - We suggest for the first time the use of gamma-valerolactone (GVL)/H2 O as
      solvent and reaction medium for the fractionation of wood to recover pure
      cellulose, uniform sugar components from hemicellulose, and a pure lignin
      fraction. The yield of the pulp residue could reach 40.3 % with a high cellulose
      purity of 90.3 %. 

PMID- 25370305
TI  - Nano-confined squaraine dye assemblies: new photoacoustic and near-infrared
      fluorescence dual-modular imaging probes in vivo.
AB  - For the purpose of near-infrared (NIR) fluorescence and photoacoustic (PA)
      tomography dual-modular imaging, self-assembly of squaraine (SQ) dyes is
      constructed in the hydrophobic phospholipid bilayers of liposomes (SQ?L) with
      variable mixing ratios of SQ and phospholipids from 1:500 to 1:10 (w/w). When
      doping minimal amounts of SQ, molecularly dispersed SQ in bilayers shows
      remarkable fluorescence. Interesting, the PA signal is enhanced with increase of
      SQ in the nanoconfined bilayer region, which is attributed to the formation of SQ
      based H-aggregates and enhanced thermal conversion efficiency (eta). SQ?L shows
      satisfactory chemical and thermal stabilities and photobleaching resistance. SQ?L
      is well-distributed in the cytoplasm of MCF-7 cells and its fluorescence signal
      remains for 7 days without dramatic quenching owing to the good stability of
      SQ?L. Furthermore, SQ?L is subjected to in vivo NIR fluorescence imaging to
      evaluate the whole-body biodistribution in organ level. Particularly, PA imaging
      with deeper tissue penetration capability is utilized to investigate the
      heterogeneous distribution SQ?L inside solid tumor. The majority of SQ?L are
      enriched in the area where the blood vessels are generated, implying that the
      liposomal nanocarriers exhibit lower tumor tissue penetration capability after
      the vascular leakage. This result is validated by histological examination of
      tumor tissue in parallel. 

PMID- 25370302
TI  - Increased body fat mass and tissue lipotoxicity associated with ovariectomy or
      high-fat diet differentially affects bone and skeletal muscle metabolism in rats.
AB  - PURPOSE: The aim of this study was to evaluate and compare the musculoskeletal
      effects induced by ovariectomy-related fat mass deposition against the
      musculoskeletal effects caused by a high-fat diet. METHODS: A group of adult
      female rats was ovariectomized and fed a control diet. Two additional groups were
      sham-operated and fed a control or a high-fat diet for 19 weeks. Distal femur and
      serum bone parameters were measured to assess bone metabolism. Muscle protein
      metabolism, mitochondrial markers and triglyceride content were evaluated in
      tibialis anterior. Triglyceride content was evaluated in liver. Circulating
      inflammatory and metabolic markers were determined. RESULTS: The high-fat diet
      and ovariectomy led to similar increases in fat mass (+36.6-56.7%; p < 0.05) but
      had different impacts on bone and muscle tissues and inflammatory markers.
      Consumption of the high-fat diet led to decreased bone formation (-38.4%; p <
      0.05), impaired muscle mitochondrial metabolism, muscle lipotoxicity and a 20.9%
      increase in tibialis anterior protein synthesis rate (p < 0.05). Ovariectomy was
      associated with higher bone turnover as bone formation increased +72.7% (p <
      0.05) and bone resorption increased +76.4% (p < 0.05), leading to bone loss, a
      17.9% decrease in muscle protein synthesis rate (p < 0.05) and liver
      lipotoxicity. CONCLUSIONS: In female rats, high-fat diet and ovariectomy
      triggered similar gains in fat mass but had different impacts on bone and muscle
      metabolism. The ovariectomy-induced mechanisms affecting the musculoskeletal
      system are mainly caused by estrogen depletion, which surpasses the potential
      independent effect of adiposity.

PMID- 25370307
TI  - Primary penile adenocarcinoma with concurrent hypercalcaemia of malignancy in a
      dog.
AB  - A 13-year-old male neutered Siberian husky crossbreed dog was presented with a 3
      week history of haematuria and penile swelling. Clinical examination and computed
      tomography demonstrated a soft-tissue mass located at the base of the penis
      without signs of other primary tumours or metastasis. Clinicopathological
      findings revealed paraneoplastic hypercalcaemia. Fine-needle aspiration cytology
      of the mass suggested an epithelial tumour with several criteria of malignancy
      present. Following surgical excision of the mass, the hypercalcaemia resolved.
      Histopathology and immunohistochemistry revealed features consistent with an
      adenocarcinoma. Despite thorough examination, no perineal or anal sac tumour was
      found. To the authors' knowledge, this is the first reported case of a penile
      adenocarcinoma with hypercalcaemia of malignancy. 

PMID- 25370306
TI  - Preen secretions encode information on MHC similarity in certain sex-dyads in a
      monogamous seabird.
AB  - Animals are known to select mates to maximize the genetic diversity of their
      offspring in order to achieve immunity against a broader range of pathogens.
      Although several bird species preferentially mate with partners that are
      dissimilar at the major histocompatibility complex (MHC), it remains unknown
      whether they can use olfactory cues to assess MHC similarity with potential
      partners. Here we combined gas chromatography data with genetic similarity
      indices based on MHC to test whether similarity in preen secretion chemicals
      correlated with MHC relatedness in the black-legged kittiwake (Rissa tridactyla),
      a species that preferentially mates with genetically dissimilar partners. We
      found that similarity in preen secretion chemicals was positively correlated with
      MHC relatedness in male-male and male-female dyads. This study provides the first
      evidence that preen secretion chemicals can encode information on MHC relatedness
      and suggests that odor-based mechanisms of MHC-related mate choice may occur in
      birds. 

PMID- 25370309
TI  - Functionalised gold and titania nanoparticles and surfaces for use as
      antimicrobial coatings.
AB  - We report the preparation, characterisation and antimicrobial functional testing
      of various titanium dioxide and gold modified titanium dioxide nanoparticles
      embedded into a polysiloxane polymer by a swell dip-coating procedure. We show
      that the surfaces are effective in killing both Gram-positive (Staphylococcus
      aureus) and Gram-negative (Escherichia coli) bacteria under different lighting
      conditions. The presence of the nanoparticles was of critical importance in
      improving the functional properties of the surface. These materials have the
      potential to reduce hospital-acquired infection, by killing bacteria on the
      polymer surface. 

PMID- 25370308
TI  - Biological evaluation of porous aliphatic polyurethane/hydroxyapatite composite
      scaffolds for bone tissue engineering.
AB  - Biomaterial scaffolds meant to function as supporting structures to osteogenic
      cells play a pivotal role in bone tissue engineering. Recently, we synthesized an
      aliphatic polyurethane (PU) scaffold via a foaming method using non-toxic
      components. Through this procedure a uniform interconnected porous structure was
      created. Furthermore, hydroxyapatite (HA) particles were introduced into this
      process to increase the bioactivity of the PU matrix. To evaluate the biological
      performances of these PU-based scaffolds, their influence on in vitro cellular
      behavior and in vivo bone forming capacity of the engineered cell-scaffold
      constructs was investigated in this study. A simulated body fluid test
      demonstrated that the incorporation of 40 wt % HA particles significantly
      promoted the biomineralization ability of the PU scaffolds. Enhanced in vitro
      proliferation and osteogenic differentiation of the seeded mesenchymal stem cells
      were also observed on the PU/HA composite. Next, the cell-scaffold constructs
      were implanted subcutaneously in a nude mice model. After 8 weeks, a considerable
      amount of vascularized bone tissue with initial marrow stroma development was
      generated in both PU and PU/HA40 scaffold. In conclusion, the PU/HA composite is
      a potential scaffold for bone regeneration applications.

PMID- 25370310
TI  - Her belly button is leaking: a case of patent urachus.
AB  - Patent urachus is one of the least commonly seen of the urachal anomalies. In
      this report, we present a case of a patent urachus in a15-day-old female who
      presented with leakage from the umbilical site. The purpose of this article is to
      discuss the embryology, clinical manifestations, diagnosis, and management of
      patent urachus. 

PMID- 25370312
TI  - A 3D active model framework for segmentation of proximal femur in MR images.
AB  - PURPOSE: Segmentation of osseous structures from clinical MR images is difficult
      due to acquisition artifacts and variable signal intensity of bones. Segmentation
      of femoral head is required for evaluation of hip joint abnormalities such as cam
      type femoroacetabular impingement. A parametric deformable model (PDM) framework
      was developed for segmentation of 3D magnetic resonance (MR) images of the hip.
      METHOD: A two-phase segmentation scheme was implemented: (i) Radial basis
      function interpolation was performed for semi-automatic piecewise registration of
      a proximal femur atlas model to an MRI scan region of interest. User-defined
      control points on the mesh model were registered to the corresponding landmarks
      on the image. (ii) An active PDM was then used for coarse-to-fine level
      segmentation. The segmentation technique was tested using 3D synthetic image data
      and clinical MR scans of the hip with varying resolution. RESULTS: The
      segmentation method provided a mean target overlap of 0.95 and misclassification
      error of 0.035 for the synthetic data. The average target overlap was 0.88, and
      misclassification error rate was 0.12 for the clinical MRI data sets. CONCLUSION:
      A framework for segmentation of proximal femur in hip MRI scans was developed and
      tested. This method is robust to artifacts and intensity inhomogeneity and
      resistant to leakage into adjacent tissues. In comparison with slicewise
      segmentation techniques, this method features inter-slice consistency, which
      results in a smooth model of the proximal femur in hip MRI scans.

PMID- 25370313
TI  - Biomineralization in bryozoans: present, past and future.
AB  - Many animal phyla have the physiological ability to produce biomineralized
      skeletons with functional roles that have been shaped by natural selection for
      more than 500 million years. Among these are bryozoans, a moderately diverse
      phylum of aquatic invertebrates with a rich fossil record and importance today as
      bioconstructors in some shallow-water marine habitats. Biomineralizational
      patterns and, especially, processes are poorly understood in bryozoans but are
      conventionally believed to be similar to those of the related lophotrochozoan
      phyla Brachiopoda and Mollusca. However, bryozoan skeletons are more intricate
      than those of these two phyla. Calcareous skeletons have been acquired
      independently in two bryozoan clades - Stenolaemata in the Ordovician and
      Cheilostomata in the Jurassic - providing an evolutionary replicate. This review
      aims to highlight the importance of biomineralization in bryozoans and focuses on
      their skeletal ultrastructures, mineralogy and chemistry, the roles of organic
      components, the evolutionary history of bimineralization in bryozoans with
      respect to changes in seawater chemistry, and the impact of contemporary global
      changes, especially ocean acidification, on bryozoan skeletons. Bryozoan
      skeletons are constructed from three different wall types (exterior, interior and
      compound) differing in the presence/absence and location of organic cuticular
      layers. Skeletal ultrastructures can be classified into wall-parallel (i.e.
      laminated) and wall-perpendicular (i.e. prismatic) fabrics, the latter apparently
      found in only one of the two biomineralizing clades (Cheilostomata), which is
      also the only clade to biomineralize aragonite. A plethora of ultrastructural
      fabrics can be recognized and most occur in combination with other fabrics to
      constitute a fabric suite. The proportion of aragonitic and bimineralic
      bryozoans, as well as the Mg content of bryozoan skeletons, show a latitudinal
      increase into the warmer waters of the tropics. Responses of bryozoan mineralogy
      and skeletal thickness to oscillations between calcite and aragonite seas through
      geological time are equivocal. Field and laboratory studies of living bryozoans
      have shown that predicted future changes in pH (ocean acidification) combined
      with global warming are likely to have detrimental effects on calcification,
      growth rate and production of polymorphic zooids for defence and reproduction,
      although some species exhibit reasonable levels of resilience. Some key questions
      about bryozoan biomineralization that need to be addressed are identified. 

PMID- 25370311
TI  - Vascular patterning sets the stage for macro and micro hepatic architecture.
AB  - Background The liver is a complex organ with a variety of tissue components that
      require a precise architecture for optimal function of metabolic and
      detoxification processes. As a result of the delicate orchestration required
      between the various hepatic tissues, it is not surprising that impairment of
      hepatic function can be caused by a variety of factors leading to chronic liver
      disease. Results Despite the growing rate of chronic liver disease, there are
      currently few effective treatment options besides orthotopic liver
      transplantation. Better therapeutic options reside in the potential for genetic
      and cellular therapies that promote progenitor cell activation aiding de novo
      epithelial and vascular regeneration, cell replacement, or population of
      bioartificial hepatic devices. In order to explore this area of new therapeutic
      potential, it is crucial to understand the factors that promote hepatic function
      through regulating cell identities and tissue architecture. Conclusions In this
      commentary, we review the signals regulating liver cell fates during development
      and regeneration and highlight the importance of patterning the hepatic vascular
      systems to set the groundwork for the macro and micro hepatic architecture of the
      epithelium.

PMID- 25370315
TI  - Clinical characteristics and outcome of thyroid storm: a case series and review
      of neuropsychiatric derangements in thyrotoxicosis.
AB  - OBJECTIVE: The objectives of this study were (1) to describe the presentation,
      demographics, and clinical course of patients admitted for thyroid storm, and (2)
      to identify factors associated with mortality. METHODS: A retrospective review of
      subjects admitted to a single academic hospital from 2006 through 2011 was
      conducted. Medical records for all patients who were admitted with a diagnosis of
      thyrotoxicosis were systematically reviewed for clinical features of thyroid
      storm. RESULTS: A total of 28 cases were identified. Thyroid storm was the first
      clinical presentation of thyrotoxicosis in 13 patients (46.4%). Noncompliance
      with treatment was a major trigger in previously diagnosed patients, followed by
      infection. The mortality rate was 25% in this series. Cardiac manifestations were
      predominant, with >60% of patients having severe tachycardia (heart rate >140
      beats per minunte) and/or atrial fibrillation. Although central nervous system
      (CNS) involvement was less frequent (n = 8, 28.6%), CNS derangement of worse than
      mild severity was statistically associated with mortality (P = .021). There was
      good agreement between the Burch-Wartofsky Point Scale and Japanese Thyroid
      Association criteria in the diagnosis of thyroid storm in this study cohort.
      CONCLUSION: Thyroid storm was the first presentation of thyrotoxicosis in a
      significant proportion of patients, highlighting the importance of a high index
      of suspicion in an appropriate clinical context. The presence of neuropsychiatric
      manifestations appeared to portend greater risk of mortality. Prevailing evidence
      suggests that there are complex interactions between thyroid hormones and
      neurotransmitter circuits in the pathogenesis of CNS symptomology in
      thyrotoxicosis.

PMID- 25370316
TI  - Visual vignette.

PMID- 25370317
TI  - Comparison of the efficacy, adverse effects, and cost of zoledronic acid and
      denosumab in the treatment of osteoporosis.
AB  - OBJECTIVE: Injectable osteoporosis drugs are increasing in popularity due to
      their efficacy and convenient administration. In this retrospective comparison of
      the two available treatments, denosumab (Prolia(r)) and zoledronic acid (ZA,
      Reclast(r)), we aimed to determine and compare the efficacy and tolerability of
      denosumab and ZA. METHODS: The charts of patients who received denosumab and ZA
      at Loyola Hospital were reviewed, and adverse events were noted. Of primary
      interest were myalgias, flu-like symptoms, back pain, and fractures. A
      questionnaire regarding the efficacy, tolerability, and treatment cost
      supplemented this chart review in a subset of study participants. Bone mineral
      density (BMD) changes, bone turnover markers, and questionnaire results were also
      compared. RESULTS: The study cohort consisted of 107 patients (51 denosumab, 56
      ZA). The denosumab group had a greater mean increase in spine BMD at 1 year
      (0.060 g/cm2) than the ZA group (0.021 g/cm2; P = .04). The change in femur and
      spine BMD at 1 year were not significantly different between the 2 groups. The ZA
      group had a significantly greater incidence of mild flu-like symptoms (29% ZA
      group vs. 0% denosumab group; P = .04). CONCLUSION: The denosumab group had a
      higher mean increase in spine BMD, and the ZA group had a higher incidence of flu
      like symptoms, but the study groups were statistically similar in terms of
      patient satisfaction. As denosumab is still a relatively new therapy, there were
      a limited number of patients with posttreatment data available for comparison. As
      more posttherapy data become available, it can be further investigated.

PMID- 25370319
TI  - Low Vitamin D Status is Associated with Increased Thyrotropin-Receptor Antibody
      Titer in Graves Disease.
AB  - OBJECTIVE: Vitamin D deficiency is reportedly linked to a variety of autoimmune
      diseases. However, the relationship between thyroid autoimmunity in Graves
      disease (GD) and vitamin D deficiency is unclear. The goal of this study was to
      determine whether increased thyroid hormone autoantibody titer is associated with
      vitamin D deficiency in GD patients. METHODS: A total of 70 patients with GD and
      70 matched control subjects were recruited to our study. The levels of 25
      hydroxyvitamin D (25[OH]D), calcium, parathyroid hormone (PTH), free
      triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH),
      thyrotropin-receptor antibody (TRAb), thyroid-peroxidase antibody (TPOAb), and
      thyroglobulin antibody (TGAb) in serum collected from these patients and controls
      were examined. RESULTS: The level of 25(OH)D in serum from TRAb-positive GD
      patients was significantly lower than that in serum of healthy controls or TRAb
      negative patients. However, compared with control subjects, the level of PTH in
      serum was increased in TRAb-positive GD patients. The rate of vitamin D
      deficiency (defined as serum 25[OH]D <50 nmol/L) in TRAb-positive GD patients was
      significantly higher than in healthy controls or TRAb-negative GD patients. The
      level of 25(OH)D in serum was inversely correlated with TRAb titer in serum of
      TRAb-positive GD patients. However, our results did not show a correlation
      between 25(OH)D level and the levels of TPOAb, TGAb, FT3, FT4, or TSH.
      CONCLUSION: Low vitamin D status is associated with increased TRAb titer in GD,
      suggesting a possible link between vitamin D status and increased thyroid
      autoimmunity in GD patients.

PMID- 25370321
TI  - Early Identification of Individuals with Poorly Controlled Diabetes Undergoing
      Elective Surgery: Improving A1C Testing in the Preoperative Period.
AB  - OBJECTIVE: To describe a process improvement strategy that increased the
      identification of individuals with poorly controlled diabetes (glycated
      hemoglobin [A1C] >=8%) undergoing elective surgery at a major academic medical
      center and increased their access to specialist care. METHODS: An algorithm was
      developed to ensure A1C measurements were obtained as per the American
      Association of Clinical Endocrinologists/American Diabetes Association (AACE/ADA)
      guidelines. The diabetes management team worked collaboratively with
      anesthesiologists, surgeons, and preoperative nurse practitioners to improve the
      glycemic control of patients with an A1C >=8%. RESULTS: Before implementing the
      program, A1C testing was recorded in 854 out of 2,335 (37%) patients with
      diabetes seen in the preoperative clinic from January 1, 2011 to December 31,
      2012. The program was instituted in February 2013. From February 2013 to February
      2014, A1C testing occurred in 1,236 out of 1,334 (93%) patients with diabetes.
      After excluding those scheduled for same day surgery, 228 patients were
      considered high risk with A1C >=8%, and 175 were available for endocrine
      preoperative consultation. The program led to significant blood glucose level
      improvements on the day of surgery. CONCLUSION: A process improvement strategy to
      evaluate and treat diabetes in the preoperative period of elective surgery
      patients was implemented by a multidisciplinary team (endocrinologists, nurse
      practitioners, anesthesiologists, and surgeons) and resulted in a substantial
      improvements in obtaining A1C tests, access to specialist diabetes care, and
      glycemic control on the day of surgery. The impact of improved glycemic control
      on hospital and surgical outcomes needs further evaluation.

PMID- 25370322
TI  - Insulin Lispro with Continuous Subcutaneous Insulin Infusion is Safe and
      Effective in Patients with Type 2 Diabetes: A Randomized Crossover Trial of
      Insulin Lispro Versus Insulin Aspart.
AB  - OBJECTIVE: This study provides clinical information regarding the use of insulin
      lispro versus insulin aspart in continuous subcutaneous insulin infusion (CSII)
      in adult patients with type 2 diabetes mellitus (T2D). METHODS: After a 2-week
      lead-in period, 122 subjects treated with CSII therapy were randomized to 32
      weeks of treatment during 2 separate 16-week treatment periods (TPs) with
      crossover beginning with insulin lispro (n = 60) or insulin aspart (n = 62).
      Glycated hemoglobin A1c (HbA1c), total daily insulin dose, and weight were
      recorded at the end of TP1 and TP2. Adverse events (AEs) and hypoglycemic events
      (overall, documented symptomatic, nocturnal, or severe) were recorded throughout
      the TPs. Data were analyzed using statistical methods that accounted for repeated
      measurements. RESULTS: A total of 107 subjects completed the study; 7
      discontinued in TP1 and 8 discontinued in TP2. Insulin lispro was noninferior to
      insulin aspart in endpoint (weeks 16 and 32) HbA1c over TP1 and TP2 combined.
      Total daily insulin dose, weight change, and incidence and rates of hypoglycemia
      were not statistically significantly different between treatments. One case of
      severe hypoglycemia and 1 of diabetic ketoacidosis was observed with insulin
      aspart. One case of severe infusion site abscess was noted with insulin lispro.
      Overall, both insulin lispro and insulin aspart were well tolerated with similar
      AEs reported. CONCLUSION: Insulin lispro and insulin aspart performed similarly
      after 16 weeks of treatment, with noninferiority for HbA1c and no significant
      difference in parameters measured. These findings indicate that insulin lispro
      and insulin aspart can both be used safely and effectively in patients with T2D
      using CSII.

PMID- 25370323
TI  - Fixed-dose combination therapy in type 2 diabetes mellitus.
AB  - OBJECTIVE: The management of type 2 diabetes mellitus (T2DM) often requires
      combinations of antihyperglycemic medications with complementary mechanisms of
      action. Inadequate adherence to combination therapy, possibly related to pill
      burden (greater number of pills and higher administration frequency) and poor
      tolerability, may lead to suboptimal clinical outcomes. One potential means of
      addressing these problems is the use of fixed-dose combinations (FDCs) that
      simplify the treatment regimen by reducing pill burden compared with the same
      combination delivered as separate pills. The present study evaluates the efficacy
      and tolerability of FDCs in the treatment of T2DM patients and provides an
      overview of dosing, costs, and adherence. METHODS: A review of FDCs, with
      particular attention to those that contain metformin extended-release (XR) and
      allow once-daily dosing. RESULTS: Many FDCs contain metformin as one of the
      component drugs. However, the standard immediate-release (IR) formulation of
      metformin requires twice-daily dosing and may have tolerability problems related
      to adverse gastrointestinal (GI) effects. The XR formulations of metformin can be
      administered once daily and have been shown to reduce the occurrence of GI
      effects frequently observed with metformin IR; consequently, they may have
      significant advantages for inclusion in FDCs. The long-term cost-effectiveness of
      FDCs remains to be fully determined. CONCLUSION: For patients taking metformin,
      FDCs containing metformin XR offer equivalent efficacy with reduced dose
      frequency and, potentially, fewer GI events compared with standard IR
      formulation, as well as a reduced number of pills compared with separate-pill
      regimens. By reducing pill burden and improving tolerability, FDCs may improve
      adherence.

PMID- 25370324
TI  - Vitamin D binding protein gene polymorphism as a risk factor for vitamin D
      deficiency in Thais.
AB  - OBJECTIVE: Vitamin D deficiency is related to increased risks for a number of
      diseases. To date, at least 3 candidate genes, vitamin D binding protein (VDBP)
      gene (GC), 25-hydroxylase (CYP2R1), and 7-dehydrocholesterol reductase/NAD
      synthetase 1 (DHCR7/NADSYN1), have been associated with serum 25-hydroxyvitamin D
      (25[OH]D) levels, but their influences on the prevalence of vitamin D deficiency
      in relation to other known risk factors have not been clearly defined. METHODS:
      The study assessed 4,476 individuals aged 14 to 93 years from the Thailand 4th
      National Health Examination Survey (2008-2009) and the Electricity Generating
      Authority of Thailand (EGAT) (2008) cohorts. The GC rs2282679 polymorphism on
      chromosome 4q12-q13 was genotyped by real-time polymerase chain reaction (PCR).
      Serum 25(OH)D was measured by liquid chromatography/tandem mass spectrometry.
      Vitamin D deficiency was defined as a 25(OH)D concentration <20 ng/mL. RESULTS:
      Data were expressed as mean +/- SD. There were 2,747 (61.4%) males and 1,729
      (38.6%) females in the study, with an average body mass index (BMI) of 23.7 +/-
      4.2 kg/m2 and a mean total 25(OH)D of 28.9 +/- 9.0 ng/mL. Serum 25(OH)D levels
      decreased progressively with the presence of the C allele. Using multiple
      logistic regression analysis, vitamin D deficiency was significantly associated
      with the GC rs2282679 genotype (odds ratio [OR] per C allele 1.80, 95% confidence
      interval CI 1.57-2.01), independent of established risk factors for vitamin D
      deficiency including age, sex, and BMI. CONCLUSION: A specific GC gene
      polymorphism is associated with lower 25(OH)D levels independent of age, sex, and
      adiposity in Thai subjects.

PMID- 25370325
TI  - Medical management of extrathyroidal manifestation of graves disease.
AB  - OBJECTIVE: To review preventive measures and the current medical management of
      extrathyroidal manifestation of Graves disease and to provide an overview of
      potential immune therapies. METHODS: A literature review of investigative trials
      of treatments for Graves disease and its extrathyroidal manifestations. RESULTS:
      Given new knowledge of the stages of the autoimmune cascade responsible for the
      development of these extrathyroidal manifestations, the possibility has been
      raised of performing randomized trials of agents shown to provide benefits in
      other immune conditions. Two randomized trials on the efficacy of rituximab in
      moderate-to-severe Graves ophthalmopathy have reported conflicting results.
      CONCLUSION: Additional studies of rituximab and other agents are needed before
      they become routinely used in treating Graves disease. Meanwhile, the standard
      medical therapy for moderate-to-severe ophthalmopathy is intravenous (IV) or oral
      corticosteroids and, for dermopathy, local corticosteroid application with
      occlusive dressing. Because major adverse effects such as life-threatening
      hepatic failure can occur with very high doses of IV prednisolone, the cumulative
      total dose should not exceed 8 g.

PMID- 25370327
TI  - Omitting late-night eating may cause hypoglycemia in "well controlled" basal
      insulin-treated type 2 diabetes.
AB  - OBJECTIVE: To assess hypoglycemia caused by eating the last meal of the day
      earlier or its omission in "well controlled" type 2 diabetes mellitus patients
      treated with once-nightly basal insulin. METHODS: Previously basal insulin
      titrated subjects (n = 20) (fasting plasma glucose, FPG, <110 mg/dL and no self
      reported hypoglycemia) underwent continuous glucose monitoring (CGM) during 3
      consecutive eating conditions of 3 days each; (1) usual eating, (2) the last meal
      restricted to 18:00, and (3) 1 sequential meal omitted/day thereby creating a
      fasting day after transposing the 4-hour period after a meal with that when the
      meal was omitted. One 24-hour (00:00 to 00:00) period within each eating
      condition was selected for comparison. RESULTS: The mean duration in all
      hypoglycemic ranges doubled (P = .0584 or greater) when the last meal was omitted
      or eaten at 18:09 +/- 0:39 instead of 19:43 +/- 1:01, the usual time for the
      subjects' undisturbed eating. The mean duration of hypoglycemia was greatest
      between 00:00 to 06:00 compared to the 3 other 6-hour periods of the day.
      CONCLUSIONS: Increased hypoglycemia occurs when the subject's last meal is eaten
      earlier or omitted and may not be recognized because it occurs predominately
      during sleep. When titrating basal insulin from the morning FPG, considerations
      should be given to the effect of the last meal of the day and possible
      hypoglycemia between 00:00 and 06:00 to avoid excessive basal insulin treatment.

PMID- 25370326
TI  - Long-term treatment with pegvisomant as monotherapy in patients with acromegaly:
      experience from ACROSTUDY.
AB  - OBJECTIVE: To evaluate use of pegvisomant, a growth hormone (GH) receptor
      antagonist, as monotherapy in ACROSTUDY, a global safety surveillance study set
      in 14 countries (373 sites). METHODS: A descriptive analysis of safety, magnetic
      resonance imaging (MRI) reading, and treatment outcomes in 710 subjects who
      received at least 1 pegvisomant dose as monotherapy during and up to 5 years
      follow-up in ACROSTUDY. RESULTS: Subjects received a mean of 5.4 years of
      pegvisomant and were followed in ACROSTUDY for a mean of 3.8 years. A total of
      1,255 adverse events (AEs) were reported in 345 subjects (48.6%). Serious AEs
      (SAEs) were reported in 133 (18.7%) subjects, including 22 deaths, none of which
      were attributed to pegvisomant use. Of 670 (94%) subjects with at least 1 liver
      function test (LFT) reported in ACROSTUDY, 8 (1.2%) had reported increases in
      transaminases >3 times the upper limit of normal (ULN). No liver failure was
      reported. Based on central MRI reading, 12 of 542 subjects (2.2%) had a confirmed
      increase or increase/decrease in tumor size. Injection-site reactions were
      reported in 2.3%. At 5 years of therapy, insulin-like growth factor 1 (IGF-1)
      level was reported normal in 67.5% (mean dose 17.2 mg/day) and elevated in 29.9%
      (mean dose 19.8 mg/day). Subjects on 20 mg per day or more rose from 36% at 3
      years to 41% at 5 years of therapy. CONCLUSIONS: ACROSTUDY data indicate that
      pegvisomant used as sole medical therapy is safe and effective for patients with
      acromegaly. The reported low incidence of pituitary tumor size increase and liver
      enzyme elevations are reassuring and support the positive benefit-risk of
      pegvisomant therapy.

PMID- 25370328
TI  - Retinopathy is a Strong Determinant of Atherosclerosis in Type 2 Diabetes:
      Correlation with Carotid Intima Media Thickness.
AB  - OBJECTIVE: We investigated the correlation between the severity of diabetic
      retinopathy (DR) and carotid intima media thickness (IMT) as a marker of
      atherosclerosis in patients with type 2 diabetes. METHODS: The study group
      consisted of 140 normotensive Egyptian patients (68 males and 72 females) with
      type 2 diabetes and DR. Carotid IMT was evaluated using high-resolution B-mode
      ultrasonography. DR was assessed and graded using colored fundus photography and
      fundus fluorescein angiography, as either nonproliferative DR (NPDR) or
      proliferative DR (PDR). RESULTS: Carotid IMT was greater in patients with PDR
      compared to those with NPDR (1.094 +/- 0.142 mm vs. 0.842 +/- 0.134 mm; P<.001).
      Carotid IMT showed positive correlation with diabetes duration (P<.01), systolic
      blood pressure (P<.001), diastolic blood pressure (P<.01), fasting blood glucose
      (P<.01), postprandial blood glucose (PPBG) (P<.001), glycated hemoglobin (P<.01),
      total cholesterol (P<.01), triglycerides (TGs) (P<.001), and DR (P<.0001). No
      significant difference was found between males and females in any of the studied
      parameters. Multiple regression analysis revealed that the determinants of
      carotid IMT in the studied group were age (P<.01), PPBG (P<.01), TGs (P<.001),
      and DR (P<.0001). CONCLUSION: Our study proves that both NPDR and PDR are strong
      determinants of carotid IMT and atherosclerosis in patients with type 2 diabetes.

PMID- 25370329
TI  - Increased Soluble TNF Receptor-1 and Glutathione Peroxidase may Predict Carotid
      Intima Media Thickness in Females with Cushing Syndrome.
AB  - OBJECTIVE: Cardiovascular events are the most common cause of mortality in
      Cushing syndrome (CS). This study aimed to evaluate the impact of novel factors
      on atherosclerosis in endogenous CS. METHODS: A total of 22 female patients with
      CS and 33 normal female controls underwent evaluation of fibrinogen, high
      sensitivity C-reactive protein (hsCRP), inflammatory cytokines (interleukin [IL]
      6, IL-1beta, soluble tumor necrosis factor receptor [sTNFR]-1, and sTNFR2),
      glutathione peroxidase (GPx; measure of oxidative stress), carotid intima media
      thickness (CIMT; a measure of atherosclerosis), and percent change in flow
      mediated vasodilation (%FMV) of the brachial artery, a measure of endothelial
      dysfunction. Stepwise multiple linear regressions were done after adjusting for
      variables in models 1 through 3 to evaluate their role in predicting CIMT and
      %FMV. Model 1 consisted of age and body mass index (BMI). Model 2 consisted of
      model 1 plus blood pressure (BP), fasting blood glucose (FBG), and 2-hour
      postglucose blood glucose (2hPGBG). Model 3 consisted of model 2 plus
      triglycerides and low- and high-density lipoprotein. RESULTS: Females with CS had
      significantly higher BMI, BP, FBG, 2hPGBG, total cholesterol, triglycerides,
      fibrinogen, IL-6, IL-1beta, sTNFR1, and GPx. CIMT and %FMV were significantly
      higher and lower, respectively, in CS patients. Regression analyses revealed
      sTNFR1 to be a consistent predictor of CIMT after adjusting for model 1 (beta =
      0.656; P = .004), model 2 (beta = 0.571; P = .047), and model 3 (beta = 0.683; P
      =.026). GPx was a predictor of CIMT after adjusting for model 1 (beta = 0.565; P
      = .033) and model 3 (beta = 0.756; P= .038). CONCLUSION: This study highlights
      increased CIMT and endothelial dysfunction in CS, associated with an altered
      inflammatory milieu. sTNFR1 and GPx may predict CIMT in females with CS.

PMID- 25370330
TI  - Proinflammatory and antiinflammatory attributes of fetuin-a: a novel hepatokine
      modulating cardiovascular and glycemic outcomes in metabolic syndrome.
AB  - OBJECTIVE: Fetuin-A is a novel hepatokine. The number of biologic roles
      attributed to fetuin-A has increased exponentially in the past decade. The
      objective of this review is to discuss the pathophysiology of fetuin-A action,
      its proinflammatory and antiinflammatory attributes in different biological
      systems throughout the body, and pharmacologic interventions that modulate fetuin
      A levels. METHODS: PubMed, Medline, and Embase search for articles published to
      July 2014, using the terms "alpha-2-hs-glycoprotein" [MeSH Terms] OR "alpha-2-hs
      glycoprotein" [All Fields] OR "fetuin a" [All Fields]. RESULTS: Fetuin-A is the
      endogenous ligand for Toll-like receptor-4 activation, for lipid-induced insulin
      resistance. Fetuin-A has inverse interaction with adiponectin. Increased fetuin-A
      is a risk factor for diabetes and fatty liver disease in normoglycemia and
      prediabetes. Fetuin-A is a negative acute-phase reactant in sepsis and
      endotoxemia, promotes wound healing, and is neuroprotective in Alzheimer's
      disease. Decreased fetuin-A predicts increased disease activity in obstructive
      lung disease, Crohn's disease, and ulcerative colitis. Both elevated and reduced
      fetuin-A may be linked with increased cardiovascular events. CONCLUSION: Fetuin-A
      is a pleotropic molecule with diverse (sometimes even contradictory) effects in
      different systems, brought about by interaction with a variety of receptors,
      including the insulin, transforming growth factor-beta, and a plethora of Toll
      like receptors. As a proinflammatory molecule, fetuin-A contributes to insulin
      resistance and is an important link between liver, adipose tissue, and muscles.
      Fetuin-A is neuroprotective and plays an important antiinflammatory role in
      sepsis and autoimmune disorders. Pharmacologic options are limited in modulating
      serum fetuin-A, but salsalates, curcumin, and vitamin D are promising agents of
      the future.

PMID- 25370332
TI  - Evolution, global warming, smart phones, and late-night salivary cortisol.

PMID- 25370333
TI  - Visual vignette.

PMID- 25370334
TI  - Postprandial dynamics of plasma glucose, insulin, and glucagon in patients with
      type 2 diabetes treated with saxagliptin plus dapagliflozin add-on to metformin
      therapy.
AB  - OBJECTIVE: To analyze changes in plasma glucose, insulin, and glucagon in
      relation to glycemic response during treatment with dual add-on of saxagliptin
      (SAXA) plus dapagliflozin (DAPA) to metformin XR (MET) compared with SAXA add-on
      or DAPA add-on alone to MET in patients with type 2 diabetes mellitus (T2DM)
      poorly controlled with MET. METHODS: Double-blind trial in adults with glycated
      hemoglobin (HbA1c) >=8.0 to <=12.0% randomized to SAXA 5 mg/day plus DAPA 10
      mg/day (n = 179), or SAXA 5 mg/day and placebo (n = 176), or DAPA 10 mg/day and
      placebo (n = 179) added to background MET >=1,500 mg/day. The mean change from
      baseline in the area under the curve from 0 to 180 minutes (AUC0-180 min) was
      calculated for glucose, insulin, and glucagon obtained during a liquid meal
      tolerance test (MTT). RESULTS: Glucose AUC0-180 min was reduced more from
      baseline with SAXA + DAPA + MET (-12,940 mg/dL) compared with SAXA + MET (-6,309
      mg/dL) and DAPA + MET (-11,247 mg/dL). Insulin AUC0-180 min significantly
      decreased with SAXA + DAPA + MET (-1,120 MUU/mL) and DAPA + MET (-1,019 MUU/mL)
      and increased with SAXA + MET (661 MUU/mL). Glucagon AUC0-180 min only increased
      with DAPA + MET (2,346 pg/mL). The changes in glucose (P<.0001) and insulin (P =
      .0003) AUC0-180 min correlated with change in HbA1c, whereas the change in
      glucagon AUC0-180 min did not (P = .27). CONCLUSIONS: When added to background
      MET, the combination of SAXA + DAPA provided additional reductions in glucose
      AUC0-180 min and HbA1c without the increase in insulin seen with SAXA and without
      the increase in glucagon seen with DAPA. Changes in insulin and glucose but not
      glucagon AUC0-180 min correlated with change in HbA1c.

PMID- 25370336
TI  - Axonal regeneration in early stages of sciatic nerve crush injury is enhanced by
      alpha7nAChR in rats.
AB  - This study investigated the role of alpha 7 nicotinic acetylcholine receptor
      (alpha7nAChR) in axonal regeneration after crush injury to the rat sciatic nerve.
      The time course of alpha7nAChR expression following injury was assessed by
      immunohistochemistry and western blotting, and local inflammation, as indicated
      by the expression of tumor necrosis factor (TNF)-alpha, was detected by enzyme
      linked immunosorbent assay. Axonal regeneration was evaluated by the pinch-test,
      morphometric analysis, and by measuring growth-associated protein 43 expressions.
      Local alpha7nAChR expression increased on day 1, peaked on day 3, and remained
      elevated on day 5 following nerve injuries. Prominent alpha7nAChR
      immunoreactivity was observed in Schwann cells, endothelial cells of the
      capillaries, and a small number of inflammatory cells. Application of the
      selective alpha7nAChR agonist PNU-282987 decreased TNF-alpha level and enhanced
      axonal regeneration, but this effect was blocked by concomitant treatment with
      methyllycaconitine, a alpha7nAChR antagonist. The results indicate that the local
      expression of alpha7nAChR is increased during the early stages of sciatic nerve
      injury, and application of a alpha7nAChR agonist promotes axonal regeneration by
      suppression of TNF-alpha-mediated inflammation. The alpha7nAChR can act as a
      neuroprotective agent and alpha7nAChR activation may be a useful therapeutic
      strategy to treat peripheral nerve injury. 

PMID- 25370337
TI  - Entrapping an ionic liquid with nanocarbon: the formation of a tailorable and
      functional surface.
AB  - An interface microenvironment between nanocarbon and ionic liquids (ILs) is
      presented. By an entrapping effect, a few layers of ILs can be finely deposited
      on the surface of nanocarbon, endowing amazingly tailorable surface properties.
      The entrapped IL layer, which was believed to be unable to be charred under
      pyrolysis conditions alone, can be further carbonized to a functional carbon
      layer. C, B, and N were confirmed to share the same hexagonal ring in the
      resultant layer, which provides more designable electronic properties. 

PMID- 25370335
TI  - Genic rather than genome-wide differences between sexually deceptive Ophrys
      orchids with different pollinators.
AB  - High pollinator specificity and the potential for simple genetic changes to
      affect pollinator attraction make sexually deceptive orchids an ideal system for
      the study of ecological speciation, in which change of flower odour is likely
      important. This study surveys reproductive barriers and differences in floral
      phenotypes in a group of four closely related, coflowering sympatric Ophrys
      species and uses a genotyping-by-sequencing (GBS) approach to obtain information
      on the proportion of the genome that is differentiated between species. Ophrys
      species were found to effectively lack postpollination barriers, but are strongly
      isolated by their different pollinators (floral isolation) and, to a smaller
      extent, by shifts in flowering time (temporal isolation). Although flower
      morphology and perhaps labellum coloration may contribute to floral isolation,
      reproductive barriers may largely be due to differences in flower odour
      chemistry. GBS revealed shared polymorphism throughout the Ophrys genome, with
      very little population structure between species. Genome scans for FST outliers
      identified few markers that are highly differentiated between species and
      repeatable in several populations. These genome scans also revealed highly
      differentiated polymorphisms in genes with putative involvement in floral odour
      production, including a previously identified candidate gene thought to be
      involved in the biosynthesis of pseudo-pheromones by the orchid flowers. Taken
      together, these data suggest that ecological speciation associated with different
      pollinators in sexually deceptive orchids has a genic rather than a genomic
      basis, placing these species at an early phase of genomic divergence within the
      'speciation continuum'.

PMID- 25370338
TI  - Regional reliability of quantitative signal targeting with alternating
      radiofrequency (STAR) labeling of arterial regions (QUASAR).
AB  - BACKGROUND AND PURPOSE: Quantitative signal targeting with alternating
      radiofrequency labeling of arterial regions (QUASAR) is a recent spin labeling
      technique that could improve the reliability of brain perfusion measurements.
      Although it is considered reliable for measuring gray matter as a whole, it has
      never been evaluated regionally. Here we assessed this regional reliability.
      METHODS: Using a 3-Tesla Philips Achieva whole-body system, we scanned four times
      10 healthy volunteers, in two sessions 2 weeks apart, to obtain QUASAR images. We
      computed perfusion images and ran a voxel-based analysis within all brain
      structures. We also calculated mean regional cerebral blood flow (rCBF) within
      regions of interest configured for each arterial territory distribution. RESULTS:
      The mean CBF over whole gray matter was 37.74 with intraclass correlation
      coefficient (ICC) of .70. In white matter, it was 13.94 with an ICC of .30. Voxel
      wise ICC and coefficient-of-variation maps showed relatively lower reliability in
      watershed areas and white matter especially in deeper white matter. The absolute
      mean rCBF values were consistent with the ones reported from PET, as was the
      relatively low variability in different feeding arteries. CONCLUSIONS: Thus,
      QUASAR reliability for regional perfusion is high within gray matter, but
      uncertain within white matter.

PMID- 25370340
TI  - Ligand-based molecular MRI: O-17 JJVCPE amyloid imaging in transgenic mice.
AB  - BACKGROUND: Development of molecular MR imaging (MRI) similar to PET imaging
      using contrast agents such as gadolinium as probe have been inherently hampered
      by incompatibility between potential probe (charged molecules) and membrane
      permeability. Nevertheless, considering the inherent spatial resolution limit for
      PET of 700MU, the superior microscopic resolution of MRI of 4 MU presents a
      strong incentive for research into ligand-based molecular MRI. METHODS: (17) O
      exhibits JJ vicinal coupling with a covalently bound proton in a hydroxyl group.
      This (17) O coupled proton can be ionized in water solution and interexchange
      with other water protons. This property can be utilized as "probe" in T2-weighted
      imaging and developed into ligand-based molecular MRI. We examined beta-amyloid
      distribution in human APP overexpressed transgenic mice in vivo following
      injection of (17) O labeled Pittsburg compound B ((17) O-PiB). RESULTS: JJVCPE
      imaging successfully imaged (17) O-PiB, unequivocally establishing that (17) O
      JJVCPE imaging can be developed into PET-like molecular MRI in clinical medicine.
      CONCLUSIONS: The study represents the first successful ligand-based molecular MRI
      in vivo. This is also the first in vivo amyloid imaging using MRI. High
      resolution molecular MRI with high specificity under clinical settings, such as
      in vivo microscopic imaging of senile plaque, is a foreseeable aim.

PMID- 25370339
TI  - Identifying the start of multiple sclerosis injury: a serial DTI study.
AB  - BACKGROUND: The events leading up to the development of new multiple sclerosis
      (MS) lesions on conventional imaging are unknown. The purpose of this study is to
      use diffusion tensor imaging (DTI) to investigate prelesional changes in MS to
      better understand the pathological changes that lead to lesion development.
      METHODS: Twenty-one patients with relapsing MS starting natalizumab therapy
      underwent serial DTI for 12-18 months. Regions of interest were outlined within
      normal-appearing white matter and new gadolinium-enhancing lesions that developed
      over the course of the study. Images from all time points were coregistered and
      nonparametric regression was used to assess DTI changes prior to lesion
      appearance. RESULTS: A total of 31 newly enhancing lesions were identified.
      Significant changes in transverse diffusivity (TD) (P < .001), longitudinal
      diffusivity (LD) (P = .025), mean diffusivity (MD) (P < .001), and fractional
      anisotropy (FA) (P = .04) were observed prior to gadolinium enhancement. A
      progressive increase in TD and LD occurred up to 10 months prior to lesion
      development. DTI measures in normal appearing white matter remained unchanged
      over the study period. CONCLUSIONS: A significant change in diffusion measures
      can be seen prior to gadolinium enhancement. Changes in TD drove changes in FA
      and MD, providing evidence for impaired myelin integrity prior to gadolinium
      enhancement. DTI may be a sensitive measure for early detection of inflammatory
      disease activity in MS.

PMID- 25370341
TI  - Organized hematoma developed after suboccipital craniectomy.
AB  - An organized hematoma shows a heterogeneous signal intensity on T1-and T2
      weighted images on MR imaging, reflecting variable stages of hemorrhage. Although
      rather nonspecific, precontrast CT images of an organized hematoma demonstrate
      inhomogeneous hyperdense mass with or without calcification. We report a case of
      an organized hematoma in a 44-year-old man, which developed 5 years after
      decompressive suboccipital craniectomy following acute cerebellar infarction. To
      our best knowledge, there has been no report describing organized hematoma in the
      suboccipital craniectomy site. Computed tomography and magnetic resonance imaging
      findings of the organized hematoma are shown and discussed. We believe that
      recognition of the characteristic imaging findings of the organized hematoma as
      well as consideration of the history of surgery or anticoagulation treatment
      assists in its correct diagnosis enabling an inappropriate surgery to be avoided.

PMID- 25370342
TI  - Atherosclerotic renal artery stenosis and revascularization.
AB  - Atherosclerotic renovascular disease is the most common cause of secondary
      hypertension. The patients with renovascular disease are at increased risk for
      adverse cardiac outcomes. Recent trials comparing medical therapy alone to
      medical therapy with stenting are flawed, but lay to rest any existing debate
      that unselected revascularization is unwarranted; however, revascularization may
      be appropriate in high-risk populations. Defining an appropriate population for
      revascularization is an area of ongoing study. Furthermore, delivery of optimal
      medical therapy in this population is inadequate. This review describes recent
      developments in renal artery revascularization. 

PMID- 25370343
TI  - Changes in prostaglandin E2 in patients with idiopathic overactive bladder
      syndrome after botulinum toxin type A treatment: is there a clinical benefit?
AB  - BACKGROUND: The causality of overactive bladder syndrome (OAB) is still not fully
      understood. Several studies indicate a significant increase of prostaglandin E2
      (PGE2) in patients with OAB. However, in order to clarify whether these compounds
      can help to objectify the clinical diagnosis, further studies are needed. This
      prospective study aims to analyze PGE2 blood levels (sPGE2) in patients with OAB
      before and after botulinum toxin type A (BoNT-A) therapy. METHODS: Blood samples
      were obtained from 56 patients (52y, 18-87) with idiopathic OAB. sPGE2 levels
      were measured before and 4 weeks after BoNT-A treatment by enzyme linked
      immunosorbent assay (ELISA). 31 healthy persons with normal bladder function
      served as control group (59 y, 21-72). sPGE2 was set in relation to clinical data
      and the severity of OAB (wet/dry). The statistical data analysis was performed by
      using the non-parametric Mann-Whitney U test and paired t-test. RESULTS:
      Significant higher sPGE2 levels were detected in patients with OAB compared to
      members of the control group (2750 pg/ml vs. 1674 pg/ml, p < 0.005). Furthermore
      sPGE2 levels were increased in patients with OAB wet compared to OAB dry (p
      <0.01). In 30 patients sPGE2 levels decreased significantly after BoNT-A
      treatment compared to baseline (2995 pg/ml vs. 1486 pg/ml, p <0.005). Patients
      reported an average drug effect of 9 month (0-19); incontinence pads were needed
      significantly less frequent (p < 0.05). 3 patients reported no postoperative
      effect. sPGE2 increased in two patients compared to initial levels, a single
      patient showed a remotely decreased sPGE2. Six patients were treated repeatedly
      with BoNT-A after showing an sPGE2 re-rise. CONCLUSIONS: sPGE2-level is increased
      in patients with OAB. We could prove a significant decrease of sPGE2 after BoNT-A
      treatment. In this small cohort we could demonstrate a correlation between OAB
      and sPGE2, especially in the non-responder group. The use of sPGE2 as a biomarker
      in diagnostics and follow-up after therapy seems promising. To what extent sPGE2
      can be useful as such needs to be examined prospectively in a larger population.

PMID- 25370344
TI  - Achilles tendon vibration-induced changes in plantar flexor corticospinal
      excitability.
AB  - Daily Achilles tendon vibration has been shown to increase muscle force, likely
      via corticospinal neural adaptations. The aim of the present study was to
      determine the extent by which corticospinal excitability is influenced during
      direct Achilles tendon vibration. Motor-evoked potentials (MEPs) were elicited in
      the soleus (SOL), gastrocnemius medialis (GM) and tibialis anterior (TA) by
      transcranial magnetic stimulation of the motor cortical area of the leg with and
      without Achilles tendon vibration at various frequencies (50, 80 and 110 Hz).
      Contralateral homologues were also investigated. SOL and GM MEP amplitude
      significantly increased by 226 +/- 188 and 66 +/- 39%, respectively, during
      Achilles tendon vibration, without any difference between the tested frequencies.
      No MEP changes were reported for TA or contralateral homologues. Increased SOL
      and GM MEP amplitude suggests increased vibration-induced corticospinal
      excitability independent of vibration frequency.

PMID- 25370345
TI  - A mechanism for decision rule discrimination by supplementary eye field neurons.
AB  - A decision to select an action from alternatives is often guided by rules that
      flexibly map sensory inputs to motor outputs when certain conditions are
      satisfied. However, the neural mechanisms underlying rule-based decision making
      remain poorly understood. Two complementary types of neurons in the supplementary
      eye field (SEF) of macaques have been identified that modulate activity
      differentially to interpret rules in an ocular go-nogo task, which stipulates
      that the animal either visually pursue a moving object if it intersects a visible
      zone ('go'), or maintain fixation if it does not ('nogo'). These neurons
      discriminate between go and nogo rule-states by increasing activity to signal
      their preferred (agonist) rule-state and decreasing activity to signal their non
      preferred (antagonist) rule-state. In the current study, we found that SEF
      neurons decrease activity in anticipation of the antagonist rule-state, and do so
      more rapidly when the rule-state is easier to predict. This rapid decrease in
      activity could underlie a process of elimination in which trajectories that do
      not invoke the preferred rule-state receive no further computational resources.
      Furthermore, discrimination between difficult and easy trials in the antagonist
      rule-state occurs prior to when discrimination within the agonist rule-state
      occurs. A winner-take-all like model that incorporates a pair of mutually
      inhibited integrators to accumulate evidence in favor of either the decision to
      pursue or the decision to continue fixation accounts for the observed neural
      phenomena. 

PMID- 25370347
TI  - The influence of reducing intermediate target constraints on grasp posture
      planning during a three-segment object manipulation task.
AB  - The present experiment examined the influence of final target position on grasp
      posture planning during a three-segment object manipulation task in which the
      required object orientation at the first target position was unconstrained.
      Participants grasped a cylindrical object from a home position, placed it at an
      intermediate position in a freely chosen orientation, and subsequently placed it
      at one of four final target positions. Considerable inter-individual differences
      in initial grasp selection were observed which also led to differences in final
      grasp postures. Whereas some participants strongly adjusted their initial grasp
      postures to the final target orientation, and thus showed a preference for end
      state comfort, other participants showed virtually no adjustment in initial grasp
      postures, hence satisfying initial-state comfort. Interestingly, as intermediate
      grasp postures were similar regardless of initial grasp adjustment, intermediate
      state comfort was prioritized by all participants. These results provide further
      evidence for the interaction of multiple action selection constraints in grasp
      posture planning during multi-segment object manipulation tasks. Whereas some
      constraints may take strict precedence in a given task, other constraints may be
      more flexible and weighted differently among participants. This differentiated
      weighting leads to task- and subject-specific constraint hierarchies and is
      reflected in inter-individual differences in grasp selection. 

PMID- 25370346
TI  - Prehension synergies and hand function in early-stage Parkinson's disease.
AB  - We explored the multi-digit synergies and hand performance in object
      manipulations and pressing tasks in patients with early-stage Parkinson's disease
      (PD) and healthy controls. Synergies were defined as inter-trials co-variation
      patterns among forces/moments produced by individual digits that stabilized a
      resultant mechanical variable. The subjects performed three main tasks: pressing
      (steady-state force production followed by a force pulse into the target),
      prehension (manipulation of a handheld instrumented handle imitating the action
      of taking a sip from a glass), and functional object manipulation (moving a glass
      with water as quickly and accurately as possible along a chain of targets). The
      PD patients were slower compared to controls in all three tasks. Patients showed
      smaller synergy indices in the pressing and prehension tasks. In the prehension
      tasks, patients showed elevated grip force at steady states with smaller grip
      force modulation during the handle motion. PD patients showed smaller feed
      forward synergy adjustments in preparation to the quick action in the pressing
      and (to a smaller degree) prehension tasks. Synergy indices correlated with the
      time index of performance in the functional glass-with-water task, whereas none
      of the indices correlated with the Unified PD Rating Scale part III-motor scores.
      We interpret the results as pointing at an important role of subcortical
      structures in motor synergies and their feed-forward adjustments to action. 

PMID- 25370348
TI  - Visual mislocalization during saccade sequences.
AB  - Visual objects briefly presented around the time of saccadic eye movements are
      perceived compressed towards the saccade target. Here, we investigated
      perisaccadic mislocalization with a double-step saccade paradigm, measuring
      localization of small probe dots briefly flashed at various times around the
      sequence of the two saccades. At onset of the first saccade, probe dots were
      mislocalized towards the first and, to a lesser extent, also towards the second
      saccade target. However, there was very little mislocalization at the onset of
      the second saccade. When we increased the presentation duration of the saccade
      targets prior to onset of the saccade sequence, perisaccadic mislocalization did
      occur at the onset of the second saccade. 

PMID- 25370349
TI  - Putative spinal interneurons mediating postural limb reflexes provide a basis for
      postural control in different planes.
AB  - The dorsal-side-up trunk orientation in standing quadrupeds is maintained by the
      postural system driven mainly by somatosensory inputs from the limbs. Postural
      limb reflexes (PLRs) represent a substantial component of this system. Earlier we
      described spinal neurons presumably contributing to the generation of PLRs. The
      first aim of the present study was to reveal trends in the distribution of
      neurons with different parameters of PLR-related activity across the gray matter
      of the spinal cord. The second aim was to estimate the contribution of PLR
      related neurons with different patterns of convergence of sensory inputs from the
      limbs to stabilization of body orientation in different planes. For this purpose,
      the head and vertebral column of the decerebrate rabbit were fixed and the
      hindlimbs were positioned on a platform. Activity of individual neurons from L5
      to L6 was recorded during PLRs evoked by lateral tilts of the platform. In
      addition, the neurons were tested by tilts of the platform under only the
      ipsilateral or only the contralateral limb, as well as during in-phase tilts of
      the platforms under both limbs. We found that, across the spinal gray matter,
      strength of PLR-related neuronal activity and sensory input from the ipsilateral
      limb decreased in the dorsoventral direction, while strength of the input from
      the contralateral limb increased. A near linear summation of tilt-related sensory
      inputs from different limbs was found. Functional roles were proposed for
      individual neurons. The obtained data present the first characterization of
      posture-related spinal neurons, forming a basis for studies of postural networks
      impaired by injury.

PMID- 25370350
TI  - Levels of N-terminal pro brain natriuretic peptide are enhanced in people with
      the uncomplicated metabolic syndrome: a case-cohort analysis of the population
      based Casale Monferrato study.
AB  - BACKGROUND: Both metabolic syndrome (MetS) and N-amino terminal fragment of the
      prohormone B-type natriuretic peptide (NT-proBNP) confer increased risk of
      cardiovascular diseases (CVD). We assessed if NT-proBNP levels were greater in
      people with uncomplicated MetS, who had neither CVD/chronic kidney disease (CKD)
      nor diabetes, as compared with subjects who met none of the defining criteria of
      the MetS. METHODS: A case-cohort study from the non-diabetic population-based
      Casale Monferrato study was performed, after exclusion of all subjects with
      established CVD, CKD [estimated glomerular filtration rate (eGFR) < 60
      mL/min/1.73 m(2)], and CRP values >=3 mg/L. Cases (n = 161) with MetS were
      compared with all subjects within the cohort (n = 124) who were completely free
      of any component of the MetS. Serum NT-proBNP was centrally measured by
      immunoenzymatic assay. RESULTS: NT-proBNP levels were significantly higher in
      cases than in control subjects [35.4 (15.5-98.2) vs 24.4 (11.7-49.6) pg/mL, p =
      0.014]. In logistic regression analysis, compared with NT-proBNP values in the
      lower quartiles (<=49.64 pg/mL), higher values conferred odds ratio 4.17 (1.30
      13.44) of having the MetS, independently of age, sex, microalbuminuria, CRP,
      eGFR, and central obesity. This association was evident even after the exclusion
      of hypertensive subjects. Further adjustment for log-HOMA and diastolic blood
      pressure did not modify the strength of the association, while central obesity
      was a negative confounder. CONCLUSIONS: Compared with people without any
      component of the MetS, those with uncomplicated MetS, who had neither CVD/CKD nor
      diabetes, had increased NT-proBNP values, even if they were normotensive and
      although absolute values were still in the low range. The insulin resistance
      state did not mediate this association, while central obesity was a negative
      confounder.

PMID- 25370351
TI  - Determinants of recurrence after intended curative resection for colorectal
      cancer.
AB  - Despite intended curative resection, colorectal cancer will recur in ~45% of the
      patients. Results of meta-analyses conclude that frequent follow-up does not lead
      to early detection of recurrence, but improves overall survival. The present
      literature shows that several factors play important roles in development of
      recurrence. It is well established that emergency surgery is a major determinant
      of recurrence. Moreover, anastomotic leakages, postoperative bacterial
      infections, and blood transfusions increase the recurrence rates although the
      exact mechanisms still remain obscure. From pathology studies it has been shown
      that tumors behave differently depending on their location and recur more often
      when micrometastases are present in lymph nodes and around vessels and nerves. K
      ras mutations, microsatellite instability, and mismatch repair genes have also
      been shown to be important in relation with recurrences, and tumors appear to
      have different mutations depending on their location. Patients with stage II or
      III disease are often treated with adjuvant chemotherapy despite the fact that
      the treatments are far from efficient among all patients, who are at risk of
      recurrence. Studies are now being presented identifying subgroups, in which the
      therapy is inefficient. Unfortunately, only few of these facts are implemented in
      the present follow-up programs. Therefore, further research is urgently needed to
      verify which of the well-known parameters as well as new parameters that must be
      added to the current follow-up programs to identify patients at risk of
      recurrence.

PMID- 25370352
TI  - Disproving the Peres conjecture by showing Bell nonlocality from bound
      entanglement.
AB  - Quantum entanglement has a central role in many areas of physics. To grasp the
      essence of this phenomenon, it is fundamental to understand how different
      manifestations of entanglement relate to each other. In 1999, Peres conjectured
      that Bell nonlocality is equivalent to distillability of entanglement. The
      intuition of Peres was that the non-classicality of an entangled state, as
      witnessed via Bell inequality violation, implies that pure entanglement can be
      distilled from this state, hence making it useful for quantum information
      protocols. Subsequently, the Peres conjecture was shown to hold true in several
      specific cases, and became a central open question in quantum information theory.
      Here we disprove the Peres conjecture by showing that an undistillable bipartite
      entangled state--a bound entangled state--can violate a Bell inequality. Hence
      Bell nonlocality implies neither entanglement distillability, nor non-positivity
      under partial transposition. This clarifies the relation between three
      fundamental aspects of entanglement.

PMID- 25370353
TI  - Thalidomide combined with irradiation alters the activity of two proteases.
AB  - The aim of the present study was to investigate the effects of thalidomide, a
      drug known for its anti-angiogenic and antitumor properties, at its cytotoxic
      dose previously determined as 40 ug/ml (according to four cytotoxic test
      results). The effect of the drug alone and in combination with radiotherapy using
      Cobalt 60 (60Co) at 45 Gy on the enzymatic activity of substance-P degrading A
      disintegrin and metalloproteinase (ADAM)10 and neprilysin (NEP) was investigated
      in the mouse breast cancer cell lines 4T1 and 4T1 heart metastases post-capsaicin
      (4THMpc). Thalidomide (40 ug/ml) exerted differing effects on the activities of
      ADAM10 and NEP enzymes. In 4T1 cells, 40 ug/ml thalidomide alone did not alter
      ADAM10 enzyme activity. 60Co irradiation at 45 Gy alone caused a 42% inhibition
      in ADAM10 activity, however, the inhibition increased to 89% when combined
      therapy was used. By contrast, in the 4THMpc cell line, 40 ug/ml thalidomide
      alone induced a 66.6% increase in ADAM10 enzyme activity. Radiotherapy alone and
      thalidomide with 60Co combined therapy caused a 33.3 and 40% inhibition of ADAM10
      activity, respectively. In 4T1 cells, thalidomide alone caused a 40.9% increase
      in NEP activity. Radiation therapy alone or in combination with the drug caused a
      40.7% increase in NEP activity. In more aggressive 4THMpc cells, thalidomide
      alone caused a 26.6% increase in NEP activity. Radiotherapy alone and combined
      therapy caused a 33.3 and 37% increase in enzyme activity, respectively. To the
      best of our knowledge, the present study is the first to demonstrate that
      thalidomide alone or in combination with radiotherapy exhibits significant
      cytotoxic effects on 4T1 and 4THMpc mouse breast cancer cell lines indicating
      that this drug affects the enzymatic activity of ADAM10 and NEP in vitro.

PMID- 25370354
TI  - Receipt of Regular Primary Care and Early Cancer Detection in Appalachia.
AB  - PURPOSE: The objective was to examine the impact of regular primary care
      encounters (PCE) on early breast cancer detection in an Appalachian sample of
      Medicare beneficiaries diagnosed 2006-2008. Determinants of PCE were investigated
      and a mediation analysis was conducted where PCE was a mediator to cancer stage.
      METHODS: A total of 3,589 cases were identified from Appalachian areas in
      Pennsylvania, Kentucky, Ohio, and North Carolina, and health care services were
      examined 2 months to 2 years prior to diagnosis. A regular care PCE variable was
      constructed with 4 ordinal levels: none, any, "annual," and "semi-annual."
      Association of PCE with stage, mortality and covariables was conducted using
      ordinal logistic regressions and Cox Proportional Hazards survival models.
      RESULTS: Sixty-eight percent of the cases had semi-annual PCE. Regular PCE was
      strongly associated with late-stage cancer rates (39%-13% by increasing PCE
      level, P < .0001) and 5-year all-cause mortality (42%-24%, P < .0001). Subgroup
      analysis revealed variations by hypertension and urban status, with
      nonhypertensives with no PCE being at particularly increased risk. Significant
      determinants of PCE included age, rural/urban status, comorbidity, dual Medicaid
      insurance, Appalachian region economic classification, state, select
      comorbidities, hypertension, and minimum distance to provider. Mediation analysis
      results were consistent with lower number of comorbidities leading to increased
      late cancer detection due to patients having a decreased PCE. CONCLUSION: PCE is
      an important determinant of cancer detection, with a dose-response relationship.
      Variations exist by geography and hypertension. Comorbidity may influence both
      PCE and late-stage rates with partial mediation through PCE.

PMID- 25370355
TI  - Clinical spectrum of impulse control disorders in Parkinson's disease.
AB  - Impulse control disorders (ICDs), including compulsive gambling, buying, sexual
      behavior, and eating, are a serious and increasingly recognized psychiatric
      complication in Parkinson's disease (PD). Other impulsive-compulsive behaviors
      (ICBs) have been described in PD, including punding (stereotyped, repetitive,
      purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive PD
      medication overuse). ICDs have been most closely related to the use of dopamine
      agonists (DAs), perhaps more so at higher doses; in contrast, DDS is primarily
      associated with shorter-acting, higher-potency dopaminergic medications, such as
      apomorphine and levodopa. Possible risk factors for ICDs include male sex,
      younger age and younger age at PD onset, a pre-PD history of ICDs, and a personal
      or family history of substance abuse, bipolar disorder, or gambling problems.
      Given the paucity of treatment options and potentially serious consequences, it
      is critical for PD patients to be monitored closely for development of ICDs as
      part of routine clinical care.

PMID- 25370356
TI  - Individual and Partner Correlates of Sexual Satisfaction and Relationship
      Happiness in Midlife Couples: Dyadic Analysis of the International Survey of
      Relationships.
AB  - The current research reports a dyadic analysis of sexual satisfaction,
      relationship happiness, and correlates of these couple outcomes in a large
      multinational dataset consisting of 1,009 midlife heterosexual couples (2,018
      individuals) recruited in Japan, Brazil, Germany, Spain, and the United States
      (Heiman et al., 2011). Actor-Partner Interdependence Models (Kenny, Kashy, &
      Cook, 2006) identified correlates of sexual satisfaction that included
      individuals' reports of good health; frequent kissing, cuddling, and caressing;
      frequent recent sexual activity; attaching importance to one's own and one's
      partner's orgasm; better sexual functioning; and greater relationship happiness.
      Even after controlling for individual-level effects, partners' reports of good
      health; frequent kissing, cuddling, and caressing; frequent recent sexual
      activity; attaching importance to one's own and one's partner's orgasm; better
      sexual functioning; and greater relationship happiness contributed significantly
      to predicting and understanding individuals' sexual satisfaction. Correlates of
      relationship happiness included individuals' reports of good health; frequent
      kissing, cuddling, and caressing; frequent recent sexual activity; attaching
      importance to one's own and one's partner's orgasm; better sexual functioning;
      and greater sexual satisfaction, and once again, even after controlling for
      individual-level effects, partners' reports of each of these correlates
      contributed significantly to predicting and understanding individuals'
      relationship happiness. Interactions of individual and partner effects with
      participant gender are also reported. Current results demonstrate empirically
      that the partner "matters" to an individual's sexual satisfaction and
      relationship happiness and indicate that a comprehensive understanding of factors
      contributing to these couple outcomes requires a couple-level research strategy.
      Partner effects, even when controlling for individual effects, were consistently
      observed, and explanation of sexual satisfaction and relationship happiness
      always depended on identifying and understanding mutual and concurrent individual
      and partner influences. 

PMID- 25370357
TI  - Contextual influences on ethnic identity formation: a case study of second
      generation Korean Americans Baby Boomers in midlife.
AB  - This paper details a study on ethnic identity in midlife, illuminating identity
      formation as a complex life course phenomenon. The study addresses the importance
      of ethnic identity in understanding the experiences of racial and ethnic Baby
      Boomers as both recipients of care and as caregivers to their aging parents
      (first generation immigrants). Using a case study of second-generation Korean
      American Baby Boomers, the primary aims of this study are: (a) to explore how the
      relationship between age and race/ethnicity influences identity formation, and
      (b) how contexts influence ethnic identity formation. Findings reveal that
      cumulative experiences over earlier developmental years resulted in resolutions
      to appreciate their ethnic identity at midlife. Increasing racial and ethnic
      diversity in the U.S., combined with the large number of aging Baby Boomers,
      necessitate recognition of the cultural and racial differences within the Baby
      Boomer generation. 

PMID- 25370358
TI  - Synergistic anticancer activity of photo- and chemoresponsive nanoformulation
      based on polylysine-functionalized graphene.
AB  - Multimodal therapeutic agents based on nanomaterials for cancer combination
      therapy have attracted increasing attention. In this report, a novel photo- and
      chemoactive nanohybrid was fabricated by assembling photosensitizer Zn(II)
      phthalocyanine (ZnPc) and anticancer drug doxorubicin (DOX) on the biocompatible
      poly-l-lysine (PLL)-grafted graphene (G-PLL). This nanocomplex of G-PLL/DOX/ZnPc
      showed excellent physiochemical properties, including high solubility and
      stability in biological solutions, high drug loading efficiency, pH-triggered
      drug release, and ability to generalize (1)O2 under light excitation. Compared to
      free drug molecules, cells treated with G-PLL/DOX/ZnPc showed a higher cellular
      uptake. In particular, G-PLL/DOX/ZnPc elicited a remarkable synergistic
      anticancer activity owing to combined photodynamic and chemotherapeutic effects.
      The combination dose reduction indexes revealed that combining DOX with ZnPc
      provided strong synergistic effects (combination index < 0.1) against three
      cancer cell lines tested (HeLa, MCF-7, and B16). Thus, this study demonstrates
      programmable dual-modality therapy exemplified by G-PLL/DOX/ZnPc to
      synergistically treat cancers.

PMID- 25370360
TI  - [Ear diseases and diabetes mellitus].
AB  - In the literature there is very little information about the importance of
      diabetes mellitus for ear diseases. Therefore, this article gives an overview
      about contact points between endocrinological and otological problems in patients
      with diseases of the ear and pre-existing diabetes mellitus. In particular the
      focus is on the impact of diabetes mellitus on patients with external otitis,
      malignant external otitis, otitis media, sudden sensorineural hearing loss and
      slowly progressive hearing loss. Diseases, such as osteomyelitis of the lateral
      skull base, sudden and slowly progressive hearing loss are also discussed in
      detail. 

PMID- 25370359
TI  - Effect of weight maintenance on symptoms of knee osteoarthritis in obese
      patients: a twelve-month randomized controlled trial.
AB  - OBJECTIVE: To compare results of obese patients with knee osteoarthritis (OA)
      who, after an intensive weight loss regimen, received 1 year of either dietary
      support (D), a knee-exercise program (E), or "no attention" (C; control group).
      METHODS: We conducted a randomized, 2-phase, parallel-group trial. A total of 192
      obese participants with knee OA were enrolled; the mean age was 62.5 years and
      81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants
      were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810
      and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss.
      Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes
      were changes from randomization in pain on a 100-mm visual analog scale, weight,
      and response according to the Outcome Measures in Rheumatology-Osteoarthritis
      Research Society International criteria. RESULTS: Mean weight loss for phase 1
      was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower
      weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the
      E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by
      analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups
      had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with
      no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26
      (41%), and 33 (52%) participants responded to treatment in the D, E, and C
      groups, respectively, with no statistically significant difference in the number
      of responders (P = 0.41). CONCLUSION: A significant weight reduction with a 1
      year maintenance program improves knee OA symptoms irrespective of maintenance
      program.

PMID- 25370361
TI  - Instability of 24-hour intraocular pressure fluctuation in healthy young
      subjects: a prospective, cross-sectional study.
AB  - BACKGROUND: Elevated intraocular pressure (IOP) is a major risk factor for the
      development and/or progression of glaucoma, and a large diurnal IOP fluctuation
      has been identified as an independent risk factor of glaucoma progression.
      However, most previous studies have not considered the repeatability of 24-hour
      IOP measurements. The aim of this study was to evaluate the instability of 24
      hour IOP fluctuations in healthy young subjects. METHODS: Ten healthy young
      volunteers participated in this prospective, cross-sectional study. Each subject
      underwent 24-hour IOP and systolic/diastolic blood pressure (SBP/DBP) assessments
      both in sitting and supine positions every 3 hours, once a week for 5 consecutive
      weeks. Mean ocular perfusion pressure (MOPP) was then calculated for both
      positions. The intraclass correlation coefficients (ICCs) of maximum, minimum,
      and fluctuation parameters were computed for IOP, SBP/DBP, and MOPP. Fluctuation
      was defined as the difference between maximum and minimum values during a day.
      RESULTS: Among the serial measurements taken over a 24-hour rhythm, the
      maximum/minimum values of IOP, as well as BP, showed excellent agreement:
      regardless of position, all ICC values were over 0.800. Most of the BP
      fluctuation values also showed excellent agreement. IOP fluctuation, however, did
      not show excellent agreement; the ICC of sitting IOP fluctuation was just 0.212.
      MOPP fluctuation also showed poor agreement, especially in the sitting position
      (ICC, 0.003). CONCLUSION: On a day to day basis, 24-hour IOP fluctuations were
      not highly reproducible in healthy young volunteers. Our results imply that a
      single 24-hour IOP assessment may not be a sufficient or suitable way to
      characterize circadian IOP fluctuations for individual subjects.

PMID- 25370362
TI  - A multiscale approach to the adsorption of core-shell nanoparticles at fluid
      interfaces.
AB  - Self-assembly of colloidal particles at liquid-liquid interfaces is a process
      with great potential for the creation of controlled structures, due to the
      trapping of the particles in the plane of the interface combined with their
      lateral mobility. Here we present a multiscale characterisation of the adsorption
      and interfacial behaviour of core-shell iron oxide-poly(ethylene glycol)
      nanoparticles at a water-n-decane interface using three complementary, in situ,
      methods, which span many different length scales. First, dynamic interfacial
      measurements are taken to follow the adsorption of particles from the bulk
      aqueous phase to the interface. The mechanical properties of the interface are
      then probed using micron-sized tracers in probe-particle tracking and nano
      tracers in fluorescence correlation spectroscopy. The results show that the rate
      of particle adsorption to the interface scales with the square of bulk
      concentration, as predicted by a recent model. In addition, we show that despite
      full monolayers of nanoparticles forming, the interface remains unexpectedly
      fluid, with only a slowing of tracer particle mobility but no evidence of
      interface jamming as seen for hard nanoparticles. Our results illustrate that
      nanoparticles stabilised by soft, extended polymeric shells, display distinct
      features at fluid interfaces that can be harnessed for the fabrication of
      functional materials. 

PMID- 25370363
TI  - MicroRNA-144 suppresses tumorigenesis of hepatocellular carcinoma by targeting
      AKT3.
AB  - Aberrant expression of microRNAs (miRNAs) has been shown to be associated with
      the progression and metastasis of cancer. Dysregulation of miR-144 has been
      observed in numerous types of cancer; however, the exact role of miR-144 in
      hepatocellular carcinoma (HCC) remains unclear. The present study observed that
      miR-144 was downregulated in HCC tissues and cell lines. Forced overexpression of
      miR-144 suppressed proliferation, migration and invasion of HCC cells. AKT3 was
      identified as a direct target of miR-144 in HCC, and this was confirmed by a
      luciferase activity assay and western blot analysis. Overexpression of AKT3 in
      miR-144 transfected HCC cells effectively reversed the tumor suppressive effects
      of miR-144. Furthermore, AKT3 expression levels were inversely correlated with
      miR-144 expression levels in HCC tissues. In conclusion, the results of the
      present study suggest that miR-144 may act as a tumor suppressor in HCC by
      targeting AKT3, and miR-144 may be a potential therapeutic candidate for HCC.

PMID- 25370365
TI  - Validity in the diagnosis of reactive hemophagocytic syndrome: comment on the
      article by Fardet et Al.

PMID- 25370364
TI  - Manualised Cognitive Remediation Therapy for adult obesity: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Research has shown that obese individuals have cognitive deficiencies
      in executive function, leading to poor planning and impulse control, and decision
      making difficulties. An intervention that could help reduce these deficits and in
      turn help weight loss maintenance is Cognitive Remediation Therapy for Obesity
      (CRT-O). We aim to examine the efficacy of manualised CRT-O, which is intended to
      improve executive function, enhance reflective practice and help weight loss
      maintenance. METHODS/DESIGN: A randomised controlled trial (registered with the
      Australian New Zealand Clinical Trials Registry) will be conducted. First, 90
      obese adults (body mass index >30 kg/m2) in the community will receive three
      weekly sessions of a group Behaviour Weight Loss Treatment (BWLT), and then will
      be randomised either to receive CRT-O or to enter a no-treatment control group.
      CRT-O training will comprise twice-weekly sessions of 45 minutes over a 4 to 6
      week period, for a total of eight sessions. Measurement points will be at
      baseline, post CRT-O (or 4 to 6 weeks after BWLT for the no-treatment control), 3
      months post treatment and 1 year post treatment. The primary outcome will be
      executive function and secondary outcome measures will include participants' body
      mass index, hip to waist ratio, eating behaviours and quality of life.
      DISCUSSION: This is the first study of its kind to examine the efficacy of
      Cognitive Remediation Therapy for obese adults through a randomised controlled
      trial. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      number: 12613000537752. Date of registration: 14 May 2013.

PMID- 25370367
TI  - A fluorescent organic cage for picric acid detection.
AB  - Dynamic covalent imine chemistry has been utilized to synthesize a fluorescent
      [3+2] self-assembled nanoscopic organic cage. The fluorescent nature of the
      reduced analogue of the cage was further exploited for the highly selective
      detection of the explosive picric acid (PA). 

PMID- 25370366
TI  - Desulfosporosinus acididurans sp. nov.: an acidophilic sulfate-reducing bacterium
      isolated from acidic sediments.
AB  - Three strains of sulfate-reducing bacteria (M1(T), D, and E) were isolated from
      acidic sediments (White river and Tinto river) and characterized phylogenetically
      and physiologically. All three strains were obligately anaerobic, mesophilic,
      spore-forming straight rods, stained Gram-negative and displayed variable
      motility during active growth. The pH range for growth was 3.8-7.0, with an
      optimum at pH 5.5. The temperature range for growth was 15-40  degrees C, with an
      optimum at 30  degrees C. Strains M1(T), D, and E used a wide range of electron
      donors and acceptors, with certain variability within the different strains. The
      nominated type strain (M1(T)) used ferric iron, nitrate, sulfate, elemental
      sulfur, and thiosulfate (but not arsenate, sulfite, or fumarate) as electron
      acceptors, and organic acids (formate, lactate, butyrate, fumarate, malate, and
      pyruvate), alcohols (glycerol, methanol, and ethanol), yeast extract, and sugars
      (xylose, glucose, and fructose) as electron donors. It also fermented some
      substrates such as pyruvate and formate. Strain M1(T) tolerated up to 50 mM
      ferrous iron and 10 mM aluminum, but was inhibited by 1 mM copper. On the basis
      of phenotypic, phylogenetic, and genetic characteristics, strains M1(T), D, and E
      represent a novel species within the genus Desulfosporosinus, for which the name
      Desulfosporosinus acididurans sp. nov. is proposed. The type strain is M1(T)
      (=DSM 27692(T) = JCM 19471(T)). Strain M1(T) was the first acidophilic SRB
      isolated, and it is the third described species of acidophilic SRB besides
      Desulfosporosinus acidiphilus and Thermodesulfobium narugense. 

PMID- 25370369
TI  - UCST behavior of polyampholytes based on stoichiometric RAFT copolymerization of
      cationic and anionic monomers.
AB  - Polyampholytes with controlled equimolar ratio of charges were synthesized by
      reversible addition-fragmentation chain transfer (RAFT) copolymerization of
      cationic and anionic monomers. The resulting charge-neutral polyampholytes
      exhibit upper critical solution temperature (UCST) thermoresponsive behavior in
      ethanol-water and methanol-water solvent mixtures based on electrostatic
      attraction. Finally, the temperature induced self-assembly of a polyampholyte
      with oligo(ethylene glycol) side chains into defined nanoparticles below the UCST
      transition is demonstrated. 

PMID- 25370368
TI  - Healthcare professional requirements for the care of adult diabetes patients
      managed with insulin pumps in Australia.
AB  - BACKGROUND: Healthcare professional (HCP) time supporting insulin pump therapy
      (IPT) has not been documented, yet it is important in planning and allocating
      resources for effective care. AIM: This study aims to determine HCP time spent in
      IPT patient care to inform resource planning for optimal IPT delivery. METHODS:
      Twenty-four Australian adult IPT-experienced institutions (14 government funded,
      seven private, three both) collected data between April 2012 and January 2013
      prospectively, including: patient demographics, HCP classification, purpose of
      HCP-patient interaction, interaction mode and HCP time with the patient. A subset
      of patients was tracked from pre-pump education until stable on IPT. RESULTS:
      Data on 2577 HCP-adult patient interactions (62% face-to-face, 29% remote, 9%
      administrative) were collected over 12.2 +/- 6.4 weeks for 895 patients; age 35.4
      +/- 14.2 years; 67% female; 99% type 1 diabetes, representing 25% of all IPT
      patients of the institutions. Time (hours) spent on IPT interactions per centre
      per week were: nurses 5.4 +/- 2.8, dietitians 0.4 +/- 0.2 and doctors 1.0 +/-
      0.5. IPT starts accounted for 48% of IPT interaction time. The percentage of
      available diabetes clinic time spent on outpatient IPT interactions was 20.4%,
      4.6% and 2.7% for nurses, dietitians and doctors respectively. Fifteen patients
      tracked from pre-pump to stabilisation over 11.8 +/- 4.5 weeks, required a median
      (range) of 9.2 (3.0-20.9), 2.4 (0.5-6.0) and 1.8 (0.5-5.4) hours per patient from
      nurses, dietitians and doctors respectively. CONCLUSIONS: IPT patient care
      represents a substantial investment in HCP time, particularly for nurses. Funding
      models for IPT care need urgent review to ensure this now mainstream therapy
      integrates well into healthcare resources.

PMID- 25370370
TI  - Embolization for post-partum rupture of ovarian artery aneurysm: case report and
      review.
AB  - Spontaneous rupture of an ovarian artery aneurysm most commonly presents with
      abdominal pain in a multiparous woman in the early post-partum period. Aneurysms
      of the ovarian artery have been reported in the published work very infrequently.
      In our case, a 31-year-old multiparous woman experienced sudden left lower
      quadrant abdominal pain on the second post-partum day. Angiography showed rupture
      of a left ovarian artery aneurysm, which was successfully embolized using gelatin
      sponge particles. The patient resumed menstruation 3 months after the
      embolization and concurrently conceived, ultimately giving birth at term without
      complications. Interventional radiology appears to be a highly safe and effective
      technique for diagnosis and management of a ruptured ovarian artery aneurysm with
      minimal risk of impairing subsequent fertility. 

PMID- 25370371
TI  - Pre-clinical evaluation of the osteogenic potential of bone morphogenetic protein
      2 loaded onto a particulate porcine bone biomaterial.
AB  - AIM: The objective of study was to determine the osteogenic potential of bone
      morphogenetic protein-2 (BMP-2) loaded onto a particulate porcine bone mineral
      (PBM) biomaterial using a sinus augmentation model. METHODS: Release kinetics of
      BMP-2/PBM was determined in vitro. Eight rabbits received BMP-2/PBM or PBM alone
      into contra-lateral sinus sites. The animals were killed following a 2-week
      healing interval for micro-CT and histometrical analysis. RESULTS: Approximately
      40% of the BMP-2 was released from PBM over the first 3 days in vitro; release
      maintained at a reduced level through day 21. In vivo, total augmented implant
      volume did not differ significantly between treatments. However, local bone
      formation was enhanced in the BMP-2/PBM group compared with PBM control (10.5%
      versus 6.6%; p = 0.03), specifically in the central aspect of the PBM implant
      (14.2% versus 5.5%; p < 0.01) and adjoining the Schneiderian membrane (11.9%
      versus 5.0%; p < 0.05). There were no significant overall differences in residual
      biomaterial and fibrovascular tissue. CONCLUSION: Bone morphogenetic protein-2
      enhanced local bone formation in the rabbit maxillary sinus model following
      implantation using a PBM carrier.

PMID- 25370372
TI  - Mutational heterogeneity: a key ingredient of bet-hedging and evolutionary
      divergence?: The broad spectrum of mutations and their flexible frequency in
      populations provides a source of risk avoidance and alternative evolutionary
      strategies.
AB  - Here, we propose that the heterogeneity of mutational types in populations
      underpins alternative pathways of evolutionary adaptation. Point mutations,
      deletions, insertions, transpositions and duplications cause different biological
      effects and provide distinct adaptive possibilities. Experimental evidence for
      this notion comes from the mutational origins of adaptive radiations in large,
      clonal bacterial populations. Independent sympatric lineages with different
      phenotypes arise from distinct genetic events including gene duplication,
      different insertion sequence movements and several independent point mutations.
      The breadth of the mutational spectrum in the ancestral population should be
      viewed as a form of bet-hedging, reducing the risk of evolutionary dead ends and
      complementing the phenotypic and epigenetic heterogeneities that improve the
      survival capabilities of a population. Different mutational events arise from
      distinct cellular processes and are subject to separate environmental impacts, so
      the availability of any particular type of mutation may constrain or promote
      adaptive pathways in populations. 

PMID- 25370373
TI  - Cognitive neuroscience in space.
AB  - Humans are the most adaptable species on this planet, able to live in vastly
      different environments on Earth. Space represents the ultimate frontier and a
      true challenge to human adaptive capabilities. As a group, astronauts and
      cosmonauts are selected for their ability to work in the highly perilous
      environment of space, giving their best. Terrestrial research has shown that
      human cognitive and perceptual motor performances deteriorate under stress. We
      would expect to observe these effects in space, which currently represents an
      exceptionally stressful environment for humans. Understanding the neurocognitive
      and neuropsychological parameters influencing space flight is of high relevance
      to neuroscientists, as well as psychologists. Many of the environmental
      characteristics specific to space missions, some of which are also present in
      space flight simulations, may affect neurocognitive performance. Previous work in
      space has shown that various psychomotor functions degrade during space flight,
      including central postural functions, the speed and accuracy of aimed movements,
      internal timekeeping, attentional processes, sensing of limb position and the
      central management of concurrent tasks. Other factors that might affect
      neurocognitive performance in space are illness, injury, toxic exposure,
      decompression accidents, medication side effects and excessive exposure to
      radiation. Different tools have been developed to assess and counteract these
      deficits and problems, including computerized tests and physical exercise
      devices. It is yet unknown how the brain will adapt to long-term space travel to
      the asteroids, Mars and beyond. This work represents a comprehensive review of
      the current knowledge and future challenges of cognitive neuroscience in space
      from simulations and analog missions to low Earth orbit and beyond. 

PMID- 25370375
TI  - Prebiotic RNA synthesis by montmorillonite catalysis.
AB  - This review summarizes our recent findings on the role of mineral salts in
      prebiotic RNA synthesis, which is catalyzed by montmorillonite clay minerals. The
      clay minerals not only catalyze the synthesis of RNA but also facilitate
      homochiral selection. Preliminary data of these findings have been presented at
      the "Horizontal Gene Transfer and the Last Universal Common Ancestor (LUCA)"
      conference at the Open University, Milton Keynes, UK, 5-6 September 2013. The
      objective of this meeting was to recognize the significance of RNA in LUCA. We
      believe that the prebiotic RNA synthesis from its monomers must have been a
      simple process. As a first step, it may have required activation of the 5'-end of
      the mononucleotide with a leaving group, e.g., imidazole in our model reaction
      (Figure 1). Wide ranges of activating groups are produced from HCN under
      plausible prebiotic Earth conditions. The final step is clay mineral catalysis in
      the presence of mineral salts to facilitate selective production of functional
      RNA. Both the clay minerals and mineral salts would have been abundant on early
      Earth. We have demonstrated that while montmorillonite (pH 7) produced only
      dimers from its monomers in water, addition of sodium chloride (1 M) enhanced the
      chain length multifold, as detected by HPLC. The effect of monovalent cations on
      RNA synthesis was of the following order: Li+ > Na+ > K+. A similar effect was
      observed with the anions, enhancing catalysis in the following order: Cl- > Br- >
      I-. The montmorillonite-catalyzed RNA synthesis was not affected by hydrophobic
      or hydrophilic interactions. We thus show that prebiotic synthesis of RNA from
      its monomers was a simple process requiring only clay minerals and a small amount
      of salt. 

PMID- 25370374
TI  - Protein and Essential Amino Acids to Protect Musculoskeletal Health during
      Spaceflight: Evidence of a Paradox?
AB  - Long-duration spaceflight results in muscle atrophy and a loss of bone mineral
      density. In skeletal muscle tissue, acute exercise and protein (e.g., essential
      amino acids) stimulate anabolic pathways (e.g., muscle protein synthesis) both
      independently and synergistically to maintain neutral or positive net muscle
      protein balance. Protein intake in space is recommended to be 12%-15% of total
      energy intake (<=1.4 g?kg-1?day-1) and spaceflight is associated with reduced
      energy intake (~20%), which enhances muscle catabolism. Increasing protein intake
      to 1.5-2.0 g?kg-1?day-1 may be beneficial for skeletal muscle tissue and could be
      accomplished with essential amino acid supplementation. However, increased
      consumption of sulfur-containing amino acids is associated with increased bone
      resorption, which creates a dilemma for musculoskeletal countermeasures, whereby
      optimizing skeletal muscle parameters via essential amino acid supplementation
      may worsen bone outcomes. To protect both muscle and bone health, future
      unloading studies should evaluate increased protein intake via non-sulfur
      containing essential amino acids or leucine in combination with exercise
      countermeasures and the concomitant influence of reduced energy intake. 

PMID- 25370376
TI  - Supercritical carbon dioxide and its potential as a life-sustaining solvent in a
      planetary environment.
AB  - Supercritical fluids have different properties compared to regular fluids and
      could play a role as life-sustaining solvents on other worlds. Even on Earth,
      some bacterial species have been shown to be tolerant to supercritical fluids.
      The special properties of supercritical fluids, which include various types of
      selectivities (e.g., stereo-, regio-, and chemo-selectivity) have recently been
      recognized in biotechnology and used to catalyze reactions that do not occur in
      water. One suitable example is enzymes when they are exposed to supercritical
      fluids such as supercritical carbon dioxide: enzymes become even more stable,
      because they are conformationally rigid in the dehydrated state. Furthermore,
      enzymes in anhydrous organic solvents exhibit a "molecular memory", i.e., the
      capacity to "remember" a conformational or pH state from being exposed to a
      previous solvent. Planetary environments with supercritical fluids, particularly
      supercritical carbon dioxide, exist, even on Earth (below the ocean floor), on
      Venus, and likely on Super-Earth type exoplanets. These planetary environments
      may present a possible habitat for exotic life. 

PMID- 25370377
TI  - Three-Dimensional Algebraic Models of the tRNA Code and 12 Graphs for
      Representing the Amino Acids.
AB  - Three-dimensional algebraic models, also called Genetic Hotels, are developed to
      represent the Standard Genetic Code, the Standard tRNA Code (S-tRNA-C), and the
      Human tRNA code (H-tRNA-C). New algebraic concepts are introduced to be able to
      describe these models, to wit, the generalization of the 2n-Klein Group and the
      concept of a subgroup coset with a tail. We found that the H-tRNA-C displayed
      broken symmetries in regard to the S-tRNA-C, which is highly symmetric. We also
      show that there are only 12 ways to represent each of the corresponding
      phenotypic graphs of amino acids. The averages of statistical centrality measures
      of the 12 graphs for each of the three codes are carried out and they are
      statistically compared. The phenotypic graphs of the S-tRNA-C display a common
      triangular prism of amino acids in 10 out of the 12 graphs, whilst the
      corresponding graphs for the H-tRNA-C display only two triangular prisms. The
      graphs exhibit disjoint clusters of amino acids when their polar requirement
      values are used. We contend that the S-tRNA-C is in a frozen-like state, whereas
      the H-tRNA-C may be in an evolving state. 

PMID- 25370378
TI  - Fluorine-rich planetary environments as possible habitats for life.
AB  - In polar aprotic organic solvents, fluorine might be an element of choice for
      life that uses selected fluorinated building blocks as monomers of choice for
      self-assembling of its catalytic polymers. Organofluorine compounds are extremely
      rare in the chemistry of life as we know it. Biomolecules, when fluorinated such
      as peptides or proteins, exhibit a "fluorous effect", i.e., they are fluorophilic
      (neither hydrophilic nor lipophilic). Such polymers, capable of creating self
      sorting assemblies, resist denaturation by organic solvents by exclusion of
      fluorocarbon side chains from the organic phase. Fluorous cores consist of a
      compact interior, which is shielded from the surrounding solvent. Thus, we can
      anticipate that fluorine-containing "teflon"-like or "non-sticking" building
      blocks might be monomers of choice for the synthesis of organized polymeric
      structures in fluorine-rich planetary environments. Although no fluorine-rich
      planetary environment is known, theoretical considerations might help us to
      define chemistries that might support life in such environments. For example, one
      scenario is that all molecular oxygen may be used up by oxidation reactions on a
      planetary surface and fluorine gas could be released from F-rich magma later in
      the history of a planetary body to result in a fluorine-rich planetary
      environment. 

PMID- 25370379
TI  - Models of formation and activity of spring mounds in the mechertate-chrita-sidi
      el hani system, eastern Tunisia: implications for the habitability of Mars.
AB  - Spring mounds on Earth and on Mars could represent optimal niches of life
      development. If life ever occurred on Mars, ancient spring deposits would be
      excellent localities to search for morphological or chemical remnants of an
      ancient biosphere. In this work, we investigate models of formation and activity
      of well-exposed spring mounds in the Mechertate-Chrita-Sidi El Hani (MCSH)
      system, eastern Tunisia. We then use these models to explore possible spring
      mound formation on Mars. In the MCSH system, the genesis of the spring mounds is
      a direct consequence of groundwater upwelling, triggered by tectonics and/or
      hydraulics. As they are oriented preferentially along faults, they can be
      considered as fault spring mounds, implying a tectonic influence in their
      formation process. However, the hydraulic pressure generated by the convergence
      of aquifers towards the surface of the system also allows consideration of an
      origin as artesian spring mounds. In the case of the MCSH system, our geologic
      data presented here show that both models are valid, and we propose a combined
      hydro-tectonic model as the likely formation mechanism of artesian-fault spring
      mounds. During their evolution from the embryonic (early) to the islet ("island")
      stages, spring mounds are also shaped by eolian accumulations and induration
      processes. Similarly, spring mounds have been suggested to be relatively common
      in certain provinces on the Martian surface, but their mode of formation is still
      a matter of debate. We propose that the tectonic, hydraulic, and combined hydro
      tectonic models describing the spring mounds at MCSH could be relevant as Martian
      analogs because: (i) the Martian subsurface may be over pressured, potentially
      expelling mineral-enriched waters as spring mounds on the surface; (ii) the
      Martian subsurface may be fractured, causing alignment of the spring mounds in
      preferential orientations; and (iii) indurated eolian sedimentation and erosional
      remnants are common features on Mars. The spring mounds further bear diagnostic
      mineralogic and magnetic properties, in comparison with their immediate
      surroundings. Consequently, remote sensing techniques can be very useful to
      identify similar spring mounds on Mars. The mechanisms (tectonic and/or
      hydraulic) of formation and evolution of spring mounds at the MCSH system are
      suitable for the proliferation and protection of life respectively. Similarly,
      life or its resulting biomarkers on Mars may have been protected or preserved
      under the spring mounds. 

PMID- 25370380
TI  - A model of filamentous cyanobacteria leading to reticulate pattern formation.
AB  - The filamentous cyanobacterium, Pseudanabaena, has been shown to produce
      reticulate patterns that are thought to be the result of its gliding motility.
      Similar fossilized structures found in the geological record constitute some of
      the earliest signs of life on Earth. It is difficult to tie these fossils, which
      are billions of years old, directly to the specific microorganisms that built
      them. Identifying the physicochemical conditions and microorganism properties
      that lead microbial mats to form macroscopic structures can lead to a better
      understanding of the conditions on Earth at the dawn of life. In this article, a
      cell-based model is used to simulate the formation of reticulate patterns in
      cultures of Pseudanabaena. A minimal system of long and flexible trichomes
      capable of gliding motility is shown to be sufficient to produce stable patterns
      consisting of a network of streams. Varying model parameters indicate that
      systems with little to no cohesion, high trichome density and persistent movement
      are conducive to reticulate pattern formation, in conformance with experimental
      observations. 

PMID- 25370381
TI  - Designing with protocells: applications of a novel technical platform.
AB  - The paper offers a design perspective on protocell applications and presents
      original research that characterizes the life-like qualities of the Butschli
      dynamic droplet system, as a particular "species" of protocell. Specific focus is
      given to the possibility of protocell species becoming a technical platform for
      designing and engineering life-like solutions to address design challenges. An
      alternative framing of the protocell, based on process philosophy, sheds light on
      its capabilities as a technology that can deal with probability and whose
      ontology is consistent with complexity, nonlinear dynamics and the flow of energy
      and matter. However, the proposed technical systems do not yet formally exist as
      products or mature technologies. Their potential applications are therefore
      experimentally examined within a design context as architectural "projects"-an
      established way of considering proposals that have not yet been realized, like an
      extended hypothesis. Exemplary design-led projects are introduced, such as The
      Hylozoic Ground and Future Venice, which aim to "discover", rather than "solve",
      challenges to examine a set of possibilities that have not yet been resolved. The
      value of such exploration in design practice is in opening up a set of potential
      directions for further assessment before complex challenges are procedurally
      implemented. 

PMID- 25370382
TI  - Space Radiation: The Number One Risk to Astronaut Health beyond Low Earth Orbit.
AB  - Projecting a vision for space radiobiological research necessitates understanding
      the nature of the space radiation environment and how radiation risks influence
      mission planning, timelines and operational decisions. Exposure to space
      radiation increases the risks of astronauts developing cancer, experiencing
      central nervous system (CNS) decrements, exhibiting degenerative tissue effects
      or developing acute radiation syndrome. One or more of these deleterious health
      effects could develop during future multi-year space exploration missions beyond
      low Earth orbit (LEO). Shielding is an effective countermeasure against solar
      particle events (SPEs), but is ineffective in protecting crew members from the
      biological impacts of fast moving, highly-charged galactic cosmic radiation (GCR)
      nuclei. Astronauts traveling on a protracted voyage to Mars may be exposed to SPE
      radiation events, overlaid on a more predictable flux of GCR. Therefore, ground
      based research studies employing model organisms seeking to accurately mimic the
      biological effects of the space radiation environment must concatenate exposures
      to both proton and heavy ion sources. New techniques in genomics, proteomics,
      metabolomics and other "omics" areas should also be intelligently employed and
      correlated with phenotypic observations. This approach will more precisely
      elucidate the effects of space radiation on human physiology and aid in
      developing personalized radiological countermeasures for astronauts. 

PMID- 25370383
TI  - Rio tinto: a geochemical and mineralogical terrestrial analogue of Mars.
AB  - The geomicrobiological characterization of the water column and sediments of Rio
      Tinto (Huelva, Southwestern Spain) have proven the importance of the iron and the
      sulfur cycles, not only in generating the extreme conditions of the habitat (low
      pH, high concentration of toxic heavy metals), but also in maintaining the high
      level of microbial diversity detected in the basin. It has been proven that the
      extreme acidic conditions of Rio Tinto basin are not the product of 5000 years of
      mining activity in the area, but the consequence of an active underground
      bioreactor that obtains its energy from the massive sulfidic minerals existing in
      the Iberian Pyrite Belt. Two drilling projects, MARTE (Mars Astrobiology Research
      and Technology Experiment) (2003-2006) and IPBSL (Iberian Pyrite Belt Subsurface
      Life Detection) (2011-2015), were developed and carried out to provide evidence
      of subsurface microbial activity and the potential resources that support these
      activities. The reduced substrates and the oxidants that drive the system appear
      to come from the rock matrix. These resources need only groundwater to launch
      diverse microbial metabolisms. The similarities between the vast sulfate and iron
      oxide deposits on Mars and the main sulfide bioleaching products found in the
      Tinto basin have given Rio Tinto the status of a geochemical and mineralogical
      Mars terrestrial analogue. 

PMID- 25370384
TI  - Insights into the crystallisation process from anhydrous, hydrated and solvated
      crystal forms of diatrizoic acid.
AB  - Diatrizoic acid (DTA), a clinically used X-ray contrast agent, crystallises in
      two hydrated, three anhydrous and nine solvated solid forms, all of which have
      been characterised by X-ray crystallography. Single-crystal neutron structures of
      DTA dihydrate and monosodium DTA tetrahydrate have been determined. All of the
      solid-state structures have been analysed using partial atomic charges and
      hardness algorithm (PACHA) calculations. Even though in general all DTA crystal
      forms reveal similar intermolecular interactions, the overall crystal packing
      differs considerably from form to form. The water of the dihydrate is
      encapsulated between a pair of host molecules, which calculations reveal to be an
      extraordinarily stable motif. DTA presents functionalities that enable hydrogen
      and halogen bonding, and whilst an extended hydrogen-bonding network is realised
      in all crystal forms, halogen bonding is not present in the hydrated crystal
      forms. This is due to the formation of a hydrogen-bonding network based on
      individual enclosed water squares, which is not amenable to the concomitant
      formation of halogen bonds. The main interaction in the solvates involves the
      carboxylic acid, which corroborates the hypothesis that this strong interaction
      is the last one to be broken during the crystal desolvation and nucleation
      process. 

PMID- 25370385
TI  - Picking up the bill - improving health-care utilisation in the Democratic
      Republic of Congo through user fee subsidisation: a before and after study.
AB  - BACKGROUND: User fees have been shown to constitute a major barrier to the
      utilisation of health-care, particularly in low-income countries such as the
      Democratic Republic of Congo (DRC). Importantly, such barriers can lead to the
      exclusion of vulnerable individuals from health-care. In 2008, a donor-funded
      primary health-care programme began implementing user fee subsidisation in 20
      health zones of the DRC. In this study, we quantified the short and long-term
      effects of this policy on health-care utilisation. METHODS: Sixteen health zones
      were included for analysis. Using routinely collected health-care utilisation
      data before and after policy implementation, interrupted time series regression
      was applied to quantify the temporal impact of the user fee policy in the studied
      health zones. Payment of salary supplements to health-care workers and provision
      of free drugs - the other components of the programme - were controlled for where
      possible. RESULTS: Fourteen (88%) health zones showed an immediate positive
      effect in health-care utilisation rates (overall median increase of 19%,
      interquartile range 11 to 43) one month after the policy was introduced, and the
      effect was significant in seven zones (P <0.05). This initial effect was
      sustained or increased at 24 months in five health zones but was only significant
      in one health zone at P <0.05. Utilisation reduced over time in the remaining
      health zones (overall median increase of 4%, interquartile range -10 to 33). The
      modelled mean health-care utilisation rate initially increased significantly from
      43 consultations/1000 population to 51 consultations/1000 population during the
      first month following implementation (P <0.01). However, the on-going effect was
      not significant (P =0.69). CONCLUSIONS: Our research brings mixed findings on the
      effectiveness of user fee subsidisation as a strategy to increase the utilisation
      of services. Future work should focus on feasibility issues associated with the
      removal or reduction of user fees and how to sustain its effects on utilisation
      in the longer term.

PMID- 25370386
TI  - Epsilonvaluation of a treatment protocol for unerupted maxillary central
      incisors: retrospective clinical study of 46 children.
AB  - AIM: To evaluate the clinical outcome of a treatment protocol performed in
      children with unerupted permanent maxillary central incisors, including surgical
      removal of any related obstruction and traction initiation in one stage, under
      fully repositioned flap, combined with pre- and post-operative orthodontics for
      space creation and final alignment. METHODS: Forty-six patients aged 7.3-12.7
      years (mean = 9.44 +/- 1.36) having 54 impacted maxillary central incisors were
      reviewed. The study group included 37 patients fully treated by us and nine
      referrals with eruption failure of impacted incisors following previous surgical
      removal of various obstructions. Detailed patient's clinical and radiographic
      data were recorded. RESULTS: Aetiology of unerupted incisors included 9 patients
      with odontomas, 24 with supernumerary teeth, 1 with skeletal lack of space, 1
      with a dentigerous cyst, 4 with dilaceration, 1 with severe incisor MIH, 5 with
      luxation injuries to primary predecessors and 1 with coexisting dilaceration and
      odontoma. The total treatment time following the standardised protocol ranged
      from 5 to 21 months (mean 9.88 +/- 3.10), while the time needed using different
      approaches (no pre-operative orthodontics or obstruction removal and then to wait
      over an assessment period) ranged from 12 to 18 months (mean 15 +/- 2.12) and 17
      to 30 months (mean 23.73 +/- 5.14), respectively (p < 0.05). The time needed for
      full alignment depended on the inclination, the height of the impacted tooth (p =
      0.001) and the patient's age (p = 0.002). Additionally, the absence of pre
      operative orthodontics for space creation dramatically increased treatment time
      (p = 0.018). In contrast, the maturity of the impacted tooth and the
      developmental stage of the anterior teeth did not affect treatment time. Finally,
      when the location of the impacted tooth and the space availability allowed
      waiting for spontaneous eruption, treatment time was not statistically different
      from that of the main treatment protocol (p = 0.545). CONCLUSIONS: The studied
      treatment protocol appears ideal for successful results and minimum treatment
      time. Space creation followed by surgical removal of any obstruction together
      with orthodontic traction initiation produces excellent results, while waiting
      for spontaneous eruption is indicated only in cases of favourable patient's age
      and tooth location. Treatment initiation with operation in the absence of the
      required eruption space is not recommended, whereas in unfavourable cases
      obstruction removal without simultaneous orthodontic traction increases
      dramatically the total treatment time and requires an unnecessary second
      operation for traction.

PMID- 25370387
TI  - Drought stress affects plant metabolites and herbivore preference but not host
      location by its parasitoids.
AB  - One of the main abiotic stresses that strongly affects plant survival and the
      primary cause of crop loss around the world is drought. Drought stress leads to
      sequential morphological, physiological, biochemical and molecular changes that
      can have severe effects on plant growth, development and productivity. As a
      consequence of these changes, the interaction between plants and insects can be
      altered. Using cultivated Brassica oleracea plants, the parasitoid Microplitis
      mediator and its herbivorous host Mamestra brassicae, we studied the effect of
      drought stress on (1) the emission of plant volatile organic compounds (VOCs),
      (2) plant hormone titres, (3) preference and performance of the herbivore, and
      (4) preference of the parasitoid. Higher levels of jasmonic acid (JA) and
      abscisic acid (ABA) were recorded in response to herbivory, but no significant
      differences were observed for salicylic acid (SA) and indole-3-acetic acid (IAA).
      Drought significantly impacted SA level and showed a significant interactive
      effect with herbivory for IAA levels. A total of 55 VOCs were recorded and the
      difference among the treatments was influenced largely by herbivory, where the
      emission rate of fatty acid-derived volatiles, nitriles and (E)-4,8-dimethylnona
      1,3,7-triene [(E)-DMNT] was enhanced. Mamestra brassicae moths preferred to lay
      eggs on drought-stressed over control plants; their offspring performed similarly
      on plants of both treatments. VOCs due to drought did not affect the choice of M.
      mediator parasitoids. Overall, our study reveals an influence of drought on plant
      chemistry and insect-plant interactions. 

PMID- 25370388
TI  - Blockage of RelB expression by gene silencing enhances the radiosensitivity of
      androgen-independent prostate cancer cells.
AB  - Levels of the nuclear factor-kappa B (NF-kappaB) alternative pathway member RelB
      have been shown to correlate with the effect of radiation therapy in prostate
      cancer. RelB expression was evaluated by immunohistochemistry in normal prostate,
      benign prostate hyperplasia and prostate cancer specimens. RM-1 cells were
      pretreated with RelB siRNA prior to radiation therapy, and RelB expression in
      cytoplasmic and nuclear extracts was detected by real-time polymerase chain
      reaction and western blot analysis. The apoptotic rates of experimental RM-1 cell
      groups were assessed by flow cytometry. A clonogenic growth array was used to
      evaluate the radiosensitivity of RM-1 cell groups. The NF-kappaB family member
      RelB was expressed at a high level in prostate cancer specimens. Compared with
      irradiated control cells, RM-1 cells transfected with RelB siRNA and treated with
      radiation therapy demonstrated a significant downregulation of RelB expression in
      the cytoplasm and nucleus. Notably, flow cytometry revealed that pretreatment of
      RM-1 cells with RelB siRNA enhanced the apoptotic rate in response to radiation
      therapy compared with controls. Clonogenic growth assay results revealed enhanced
      radiosensitivity of RelB siRNA cells at various dosage points compared with
      control groups. Blockage of the alternative NF-kappaB pathway via RelB silencing
      is a promising approach to enhance the radiosensitivity of prostate cancer.

PMID- 25370389
TI  - Current trends in surgical ophthalmology.

PMID- 25370390
TI  - Correlation between the pressure-to-cornea index and both structural and
      functional measures of glaucoma.
AB  - PURPOSE: the pressure-to-cornea index (PCI) was proposed in order to integrate
      intraocular pressure and central cornea thickness as a single-risk factor for
      glaucoma. The purpose of this study was to correlate the PCI with a structural
      and two functional measures of glaucoma. SETTING: University Hospital in South
      America. MATERIALS AND METHODS: Pressure-to-cornea index was calculated for 70
      eyes of 36 subjects (glaucoma and suspects). Cup-to-disc (C/D) ratio, mean
      deviation (MD) and pattern standard deviation (PSD) as recorded by Humphrey
      automated perimetry (SITA 24-2) were correlated with PCI (Pearson's correlation
      coefficient). RESULTS: Pearson's correlation coefficient between PCI and C/D was
      0.329 (95% confidence interval [95% CI], 0.09-0.526; P = 0.006); between PCI and
      MD was - 0.356 MD (95% CI, -0.549 to - 0.126; P = 0.003); and between PCI and PSD
      was - 0.215 (95% CI, -0.433 to 0.025; P = 0.07). CONCLUSION: In addition to serve
      as a single-risk factor, PCI can be used to stage glaucoma severity as well.

PMID- 25370391
TI  - Long-term results of non-valved glaucoma drainage implant surgery and glaucoma
      drainage implant combined with trabeculectomy.
AB  - PURPOSE: The purpose was to investigate the efficacy and complications of
      nonvalved glaucoma drainage implant (GDI) surgery and GDI combined with
      trabeculectomy. SUBJECTS AND METHODS: Serial Japanese patients who received GDI
      were retrospectively investigated. The survival rate of eyes was analyzed using
      the Kaplan-Meier method, defining death as: (1) Intraocular pressure (IOP) <6
      mmHg, or >=22 mmHg, and <20% reduction of preoperative IOP, (2) additional
      glaucoma surgery, (3) loss of light perception. Prognostic factors of age, sex,
      previous surgery, type of glaucoma, synechial closure, preoperative IOP, type of
      GDI (single-, double-plate Molteno, Baerveldt 350) and GDI combined with
      trabeculectomy were investigated employing proportional hazards analysis.
      RESULTS: One hundred and twenty-four eyes of 109 patients aged 53.3 +/- 7.8 years
      old were analyzed. Types of GDI were single-plate (15.3%), double-plate Molteno
      (71.8%), and Baerveldt 350 (12.9%). The results of survival rate analysis were
      86.1, 71.1, 71.1, and 64.6% for 1, 3, 5, and 10 years respectively. Thirty-four
      eyes (27.4%) died because of uncontrolled IOP (19.4%), loss of light perception
      (5.6%), and additional glaucoma surgery (2.4%). Single-plate Molteno was the only
      risk factor for failure. Persistent unphysiological hypotony (0.8%) and bullous
      keratopathy (5.6%) were observed. CONCLUSION: Nonvalved GDI surgery and GDI
      combined with trabeculectomy using nonabsorbable tube ligature proved to be an
      excellent device for any type of glaucoma in Japanese patients. Hypotony and
      corneal endothelial loss are the most serious complication in the long-term
      results of our patients.

PMID- 25370392
TI  - Relationship between systemic hypertension, perfusion pressure and glaucoma: a
      comparative study in an adult Indian population.
AB  - AIMS: To study the relationship between blood pressure (BP), intraocular pressure
      (IOP), mean ocular perfusion pressure (MOPP) and primary open angle glaucoma
      (POAG) in patients with hypertension and compare it to a control group of
      normotensives. DESIGN: Cross-sectional observational study. MATERIALS AND
      METHODS: A total of 108 subjects with primary hypertension and 100 age-matched
      controls without hypertension were enrolled for the study. IOP measurement using
      Noncontact Tonometer and dilated fundus evaluation using + 90 D lens were done
      for all cases. Single recording of BP was taken. Gonioscopy, Humphrey's central
      visual fields, optical coherence tomography and pachymetry were done for all
      subjects with IOP > 21 mm Hg or C: D ratio >= 0.5 or asymmetry of > 0.2.
      STATISTICAL ANALYSIS: Univariate and multivariate multinomial regression models
      were used to determine the association between covariates and risk of glaucoma or
      glaucoma suspect. RESULTS: There was no difference in the glaucoma status between
      subjects with and without hypertension. Subjects on antihypertensive medications
      were 1? times more likely to have suspicious glaucoma (odds ratio [OR] =1.56] and
      nearly twice as likely to have POAG (OR = 1.85). In addition, we found a 31% and
      12% reduction in risk of having POAG (95% confidence interval [CI] =13-45%, P =
      0.001) and glaucoma suspect (95% CI = 2-21%, P = 0.03) respectively with every 1
      mm Hg increment in MOPP. CONCLUSION: Subjects on antihypertensive medications are
      more likely to have either glaucoma or glaucoma suspect, and higher ocular
      perfusion pressure offers relative protection from glaucomatous damage.

PMID- 25370393
TI  - Sutureless femtosecond anterior lamellar keratoplasty: a 1-year follow-up study.
AB  - AIM: To study the safety and efficacy of sutureless femtosecond anterior lamellar
      keratoplasty (FALK) in patients with corneal stromal opacities. MATERIALS AND
      METHODS: Eleven eyes of 11 consecutive patients with corneal stromal opacities
      involving < 250 MU due to various pathologies were included in the study.
      Preoperatively, all underwent anterior segment imaging with spectral domain
      optical coherence tomography (SD-OCT) (Bioptigen Inc., Durham, North Carolina,
      USA) to measure the depth of the stromal opacity. All patients underwent FALK,
      and bandage contact lens was placed for a period of 2 weeks. Postoperatively,
      uncorrected visual acuity, best corrected visual acuity (BCVA), and SD-OCT
      evaluation were performed. RESULTS: All patients showed significant improvement
      in BCVA. The mean postoperative BCVA (in decimals) improved from 0.11 +/- 0.06
      preoperatively to 0.59 +/- 0.08. There were no intraoperative or significant
      postoperative complications that were noticed. CONCLUSION: FALK is a safe and
      effective alternative to deep anterior lamellar keratoplasty or penetrating
      keratoplasty in the treatment of anterior stromal opacities.

PMID- 25370394
TI  - Comparison of clinical outcomes, patient, and surgeon satisfaction following
      topical versus peribulbar anesthesia for phacoemulsification and intraocular lens
      implantation: a randomized, controlled trial.
AB  - BACKGROUND: Both cataract surgery and anesthesia techniques are rapidly evolving
      to become more patient friendly. However, comparison of topical anesthesia (TA)
      and peribulbar anesthesia (PA) for phacoemulsification and cataract surgery is
      limited. We evaluated the clinical outcomes and patient and surgeon satisfaction
      between anesthetic techniques. MATERIALS AND METHODS: This randomized clinical
      trial was conducted between January and June 2012. Patients were randomly
      assigned to TA and PA groups for surgery. Visual acuity at 4 weeks
      postoperatively, status of the cornea and the wound and intraoperative
      complications were compared between groups at day 1, and 1 and 4 weeks after
      surgery. Patients and the surgeon completed a close-ended questionnaire on
      satisfaction with analgesia and comfort. The relative risk (RR) with 95%
      confidence intervals (CI) was calculated. RESULT: There were 500 patients in each
      group. There were no significant differences between groups preoperatively.
      Complications at 1-day postoperatively were significantly greater in the TA group
      (RR = 1.36, 95% CI: 1.17-1.58). Satisfaction with the mitigation of pain was
      statistically significantly greater in the PA group compared to the TA group
      (chi2 = 10.9, df = 3, P = 0.001). Surgeons were more satisfied with PA compared
      to TA (RR = 1.4, 95% CI: 1.34-1.63). There were more anesthesia-related
      complications in the PA group compared to the TA group. CONCLUSIONS: Patients who
      underwent surgery with topical anesthetic experienced lower complications by more
      pain compared to patients who underwent PA. Topical anesthetic supplemented with
      analgesic medications could help the patient and surgeon during cataract surgery.

PMID- 25370395
TI  - Comparison of two optical biometers in intraocular lens power calculation.
AB  - AIMS: To compare the consistency and accuracy in ocular biometric measurements
      and intraocular lens (IOL) power calculations using the new optical low-coherence
      reflectometry and partial coherence interferometry. SUBJECTS AND METHODS: The
      clinical data of 122 eyes of 72 cataract patients were analyzed retrospectively.
      All patients were measured with a new optical low-coherence reflectometry system,
      using the LENSTAR LS 900 (Haag Streit AG)/ALLEGRO BioGraph biometer (Wavelight.,
      AG), and partial coherence interferometry (IOLMaster V.5.4 [Carl Zeiss., Meditec,
      AG]) before phacoemulsification and IOL implantation. Repeated measurements, as
      recommended by the manufacturers, were performed by the same examiner with both
      devices. Using the parameters of axial length (AL), corneal refractive power (K1
      and K2), and anterior chamber depth (ACD), power calculations for AcrySof SA60AT
      IOL were compared between the two devices using five formulas. The target was
      emmetropia. Statistical analysis was performed using Statistical Package for the
      Social Sciences software (SPSS 13.0) with t-test as well as linear regression. A
      P value < 0.05 was considered to be statistically significant. RESULTS: The mean
      age of 72 cataract patients was 64.6 years +/- 13.4 [standard deviation]. Of the
      biometry parameters, K1, K2 and [K1 + K2]/2 values were significantly different
      between the two devices (mean difference, K1: -0.05 +/- 0.21 D; K2: -0.12 +/-
      0.20 D; [K1 + K2]/2: -0.08 +/- 0.14 D. P <0.05). There was no statistically
      significant difference in AL and ACD between the two devices. The correlations of
      AL, K1, K2, and ACD between the two devices were high. The mean differences in
      IOL power calculations using the five formulas were not statistically significant
      between the two devices. CONCLUSIONS: New optical low-coherence reflectometry
      provides measurements that correlate well to those of partial coherence
      interferometry, thus it is a precise device that can be used for the pre
      operative examination of cataract patients.

PMID- 25370396
TI  - Donor and tissue profile of a community eye bank in Eastern India.
AB  - PURPOSE: The purpose of this study is to analyze the donor and tissue profile of
      a community eye bank in Eastern India. MATERIALS AND METHODS: Eye bank records
      were analyzed for the period July 2007-June 2011. Variables analyzed included
      donor demographics (age, gender, and ethnicity), donor cause of death, consent
      for recovery, death-to-preservation interval, preservation-to-utilization
      interval, endothelial cell density (ECD), corneal suitability for
      transplantation, and corneal tissue utilization. RESULTS: During this study
      period, 743 corneal tissues were retrieved from 373 donors (male:female =
      263:110). The mean age of donors was 52 +/- 21 years (range: 3-95 years). The
      most common donor age group was 41-50 and 71-80 years. Most of the donors
      belonged to one religious faith (99%). The most common causes of death were
      cardiorespiratory failure (34%) followed by road traffic accident (30%). Majority
      donors were motivated (n = 320; 86%), and remaining (n = 53; 14%) were voluntary.
      Most of the consents were given by sons or daughters of the deceased (45%)
      followed by siblings (18%). Mean death-to-preservation interval was 3.9 +/- 1.9
      h. Mean preservation-to-utilization interval was 56.0 +/- 24.4 h. The mean ECD of
      donor corneal tissue was 2857 +/- 551 cells/mm 2 and the median value was 2898
      cells/mm 2 . Of harvested corneas 556 (75%) corneal tissues were utilized. The
      most common causes of nonutilization were septicemia in donor (n = 56; 30%) and
      poor quality of tissue (n = 55; 30%). CONCLUSIONS: Although, there is significant
      corneal tissue utilization, there is a need for increased awareness among people
      in order to augment voluntary donations.

PMID- 25370397
TI  - In vivo confocal microscopic characteristics of crystalline keratopathy in
      patients with monoclonal gammopathy: report of two cases.
AB  - In this paper, we report two cases of a 62-year-old patient presented with
      blurred vision and a 45-year-old male diagnosed with multiple myeloma who was
      referred from the Department of Oncology. Slit-lamp examination, in vivo confocal
      microscopy (IVCM), systemic work-up and serum protein electrophoresis were
      obtained. In both patients, slit-lamp findings revealed bilateral diffuse
      subepithelial and anterior stromal crystals and IVCM showed highly reflective
      deposits in the corneal epithelium and stroma. The first patient was eventually
      diagnosed with monoclonal gammopathy of undetermined significance following bone
      marrow biopsy and systemic evaluation. Unusual corneal deposits may constitute
      the first sign of monoclonal gammopathies. IVCM may be helpful in showing the
      crystalline nature of the corneal deposits and guiding the clinician to the
      diagnosis of gammopathies. Both ophthalmologists and oncologists should be aware
      that corneal deposits may herald a life-threatening hematologic disease. 

PMID- 25370398
TI  - Repeatability of retinal thickness and volume metrics in neovascular age-related
      macular degeneration using the Topcon 3DOCT-1000.
AB  - INTRODUCTION: Optical coherence tomography (OCT) is a commonly used imaging
      modality that provides detailed cross-sectional retinal images. This has
      revolutionised management of neovascular age-related macular degeneration. The
      need for repeated anti-vascular endothelial growth factor injections has led to
      therapy being delivered using OCT-guided retreatment strategies with both
      qualitative OCT features of disease activity (e.g. macular fluid) and changes in
      retinal thickness as triggers for retreatment The purpose of this study is to
      determine the intra-session repeatability of retinal thickness and volume
      measurements using the Topcon 3DOCT-1000 spectral-domain optical coherence
      tomography (SDOCT) device in patients with neovascular age-related macular
      degeneration (nAMD). This is the largest study to date looking specifically at
      the Topcon 3DOCT-1000. MATERIALS AND METHODS: Two SDOCT raster scans were
      performed by the same blinded observer in the same sitting in consecutive
      patients attending for nAMD treatment as part of standard validation of a new
      device. Retrospective analysis was undertaken, with retinal thickness and volume
      measurements automatically calculated by the onboard software for each Early
      Treatment of Diabetic Retinopathy Study subfield for each scan. Bland-Altman
      methods of analysis were used to assess repeatability. RESULTS: Data from the 73
      patients were analyzed with a mean age of 78 years (standard deviation 8). The
      95% coefficient of repeatability (CR) was 64 MUm and 0.050 mm 3 for retinal
      thickness and volume respectively in the central 1 mm macular subfield. The CR
      did not exceed 85 MUm (0.30 mm 3 ) in any subfield. The revised CR for retinal
      thickness and volume for the subgroup of 37 patients with no segmentation error
      in the central 1 mm subfield was 53 MUm and 0.050 mm 3 respectively. Discussion :
      We report relatively modest intra-sessional repeatability of SDOCT retinal
      thickness and volume metrics in patients with nAMD in a clinical setting. Though
      useful in detecting clinical change from measurement variability in clinical
      practice, these results suggest the precision of macular thickness measurement
      does not approach the theoretical resolution of SDOCT.

PMID- 25370399
TI  - Unilateral Punctate inner choroidopathy with choroidal neovascular membrane in a
      young male.

PMID- 25370400
TI  - Systemic lupus erythematosus retinopathy in a 32-year-old female: report of a
      case.

PMID- 25370401
TI  - Cataract surgery in a case of carotid cavernous fistula.
AB  - A carotid-cavernous fistula (CCF) is an abnormal communication between the
      cavernous sinus and the carotid arterial system. The ocular manifestations
      include conjunctival chemosis, proptosis, globe displacement, raised intraocular
      pressure and optic neuropathy. Although management of CCF in these patients is
      necessary, the ophthalmologist may also have to treat other ocular morbidities
      such as cataract. Cataract surgery in patients with CCF may be associated with
      many possible complications, including suprachoroidal hemorrhage. We describe
      cataract extraction surgery in 60-year-old female with bilateral spontaneous low
      flow CCF. She underwent phacoemulsification via a clear corneal route under
      topical anesthesia and had an uneventful postoperative phase and recovered
      successfully. Given the various possible ocular changes in CCF, one must proceed
      with an intraocular surgery with caution. In this communication, we wish to
      describe the surgical precautions and the possible pitfalls in cataract surgery
      in patients with CCF. 

PMID- 25370402
TI  - Michels syndrome: the first case report from India and review of literature.
AB  - A 2-year 7-month-old girl born out of a consanguineous marriage, presented at our
      facility with clinical features characterized by the eyelid triad of
      blepharophimosis, blepharoptosis and epicanthus inversus in association with
      hypertelorism, cleft palate and craniosynostosis. This constellation of features
      is suggestive of Michels syndrome. At the time of writing this report, there were
      only ten reported cases worldwide and to the best of our knowledge, there have
      been no published reports from India. 

PMID- 25370403
TI  - An unusual presentation of Pseudomonas aeruginosa blebitis following combined
      surgery.
AB  - We report a case of blebitis that occurred 3 years later following a combined
      glaucoma and cataract surgery. It was an atypical presentation, as patient had no
      classical fiery looking signs of blebitis despite the isolated organism being
      Pseudomonas aeruginosa. Improvized surgical techniques like use of Mitomycin C,
      releasable flap sutures though considered as part of the recommended procedure
      for better surgical outcomes, their role as potential risk factors for visually
      blinding complications like endophthalmitis are often overlooked. This case
      report throws light on such risk factors for bleb associated infections and
      recommends removal or trimming of all releasable sutures and the need for a
      regular postoperative follow-up. 

PMID- 25370404
TI  - Fundus imaging with a mobile phone: a review of techniques.
AB  - Fundus imaging with a fundus camera is an essential part of ophthalmic practice.
      A mobile phone with its in-built camera and flash can be used to obtain fundus
      images of reasonable quality. The mobile phone can be used as an indirect
      ophthalmoscope when coupled with a condensing lens. It can be used as a direct
      ophthalmoscope after minimal modification, wherein the fundus can be viewed
      without an intervening lens in young patients with dilated pupils. Employing the
      ubiquitous mobile phone to obtain fundus images has the potential for mass
      screening, enables ophthalmologists without a fundus camera to document and share
      findings, is a tool for telemedicine and is rather inexpensive. 

PMID- 25370405
TI  - Acute visual loss with ophthalmoplegia after spinal surgery: report of a case and
      review of the literature.
AB  - We report a case of a 15-year-old boy who presented with profound visual loss and
      complete ophthalmoplegia after an uneventful spinal surgery for removal of
      cervical osteoblastoma. Postoperative visual loss following nonocular surgery is,
      fortunately rare, yet a devastating complication. The most common cause is
      ischemic optic neuropathy, but it can also be due to central retinal occlusion or
      cortical blindness. Visual loss in conjunction with ophthalmoplegia is rarely
      seen, and there are very few reports in the literature. We also review the
      related literature and highlight the mechanism and preventive measures. 

PMID- 25370406
TI  - Brachytherapy, a viable option of globe salvage in treatment of large ciliary
      body melanocytoma.
AB  - We report a case of large histopathologically proven melanocytoma of the ciliary
      body in a 15-year-old male, presented with rapid extraocular growth following
      incisional biopsy with scleral patch graft. We chose brachytherapy with Ruthenium
      106 plaque over enucleation as the later was refused by the parents. The initial
      apical height of the tumor was 14.2 mm on ultrasonography. Two weeks after
      brachytherapy, the mass regressed to a size of 8.1 mm and 1 year later to 6.7 mm.
      This is the first case report showing the response of brachytherapy to ciliary
      body melanocytoma, which results in ocular and visual acuity salvation with
      considerable decreased in size of the tumor. The authors conclude that
      brachytherapy is an option in the management of non-resectable melanocytoma of
      the ciliary body. 

PMID- 25370407
TI  - Acquired capillary hemangioma of the eyelid in a 49-year-old woman from Turkey.
AB  - A 49-year-old woman developed a dark brown nodular mass in the lower eyelid. The
      lesion had grown fast for 2 months and then had remained stable in size.
      Excisional biopsy was performed. Histopathological examination of an excisional
      biopsy specimen pointed to proliferative vessels lined by increased endothelial
      cells without nuclear atypism. The nodular mass evaluated as a capillary
      hemangioma. 

PMID- 25370408
TI  - Regarding a novel technique to recanalize the nasolacrimal duct with
      endodiathermy bipolar probe.

PMID- 25370409
TI  - Nasolacrimal duct recanalization with endodiathermy bipolar probe: response from
      authors.

PMID- 25370410
TI  - IgE is a marker for visceral larva migrans.

PMID- 25370411
TI  - Full field perimetry in occipital lobe lesion.

PMID- 25370412
TI  - Unusual lymphoma of lacrimal gland.

PMID- 25370414
TI  - Validation of three splice donor and three splice acceptor sites for regulating
      four novel low-abundance spliced transcripts of human cytomegalovirus UL21.5 gene
      locus.
AB  - In a previous study, one spliced transcript of human cytomegalovirus (HCMV),
      named UL21.5 was identified. UL21.5 has been found to be one of the viral
      transcripts packaged within HCMV particles. The UL21.5 mRNA is translated into a
      secreted glycoprotein, which is a viral chemokine decoy receptor specifically
      interacting with regulated upon activation normal T cell expressed and secreted
      (RANTES). In the present study, four novel low-abundance 3'-coterminal spliced
      transcripts were identified to be transcribed from the UL21.5 gene region of a
      low-passage HCMV strain during the late infection phase by cDNA library
      screening, northern blot hybridization, reverse transcription polymerase chain
      reaction (RT-PCR) and rapid amplification of cDNA ends (RACE)-PCR. Three splicing
      donor and three splicing acceptor sites found in the UL21.5 gene region were
      validated to be functional in an in vitro expression system. In addition, the
      determinant regulatory region that is necessary for the splice donor site at
      nucleotide (nt) 25533 was located in a 9-bp sequence around the site; the
      regulatory regions for the splice acceptor sites at nt 26597 and nt 26633 were
      located in a 20-bp sequence upstream of the site at nt 26597 and in a 10-bp
      sequence from nt 26641 to nt 26650 downstream of the site at nt 26633,
      respectively.

PMID- 25370413
TI  - In vitro synergistic antitumor efficacy of sequentially combined
      chemotherapy/icotinib in non-small cell lung cancer cell lines.
AB  - The concurrent administration of chemotherapy and epidermal growth factor
      receptor-tyrosine kinase inhibitors (EGFR-TKIs) has previously produced a
      negative interaction and failed to confer a survival benefit to non-small cell
      lung cancer (NSCLC) patients compared with first-line cytotoxic chemotherapy. The
      present study aimed to investigate the optimal schedule of the combined treatment
      of cisplatin/paclitaxel and icotinib in NSCLC cell lines and clarify the
      underlying mechanisms. HCC827, H1975, H1299 and A549 human NSCLC cell lines with
      wild-type and mutant EGFR genes were used as in vitro models to define the
      differential effects of various schedules of cisplatin/paclitaxel with icotinib
      treatments on cell growth, proliferation, cell cycle distribution, apoptosis, and
      EGFR signaling pathway. Sequence-dependent antiproliferative effects differed
      among the four NSCLC cell lines, and were not associated with EGFR mutation,
      constitutive expression levels of EGFR or downstream signaling molecules. The
      antiproliferative effect of cisplatin plus paclitaxel followed by icotinib was
      superior to that of cisplatin or paclitaxel followed by icotinib in the HCC827,
      H1975, H1299 and A549 cell lines, and induced more cell apoptosis and G0/G1 phase
      arrest. Cisplatin and paclitaxel significantly increased the expression of EGFR
      phosphorylation in the HCC827 cell line. However, only paclitaxel increased the
      expression of EGFR phosphorylation in the H1975 cell line. Cisplatin/paclitaxel
      followed by icotinib influenced the expression of p-EGFR and p-AKT, although the
      expression of p-ERK1/2 remained unchanged. The results suggest that the optimal
      schedule of the combined treatment of cisplatin/paclitaxel and icotinib differed
      among the NSCLC cell lines. The results also provide molecular evidence to
      support clinical treatment strategies for NSCLC patients.

PMID- 25370415
TI  - PSOCUBE, a multidimensional assessment of psoriasis patients as a both
      clinically/practically sustainable and evidence-based algorithm.
AB  - BACKGROUND: There is increasing awareness of the clinical relevance of psoriasis
      comorbidities and of the importance of timely and effective screening for such
      comorbidities in the management of psoriatic patients. Previous works have
      focused on assessing evidence for prevalence of comorbidities and on the best
      available evidence for sensitivity in diagnosing suspected comorbidities. No
      algorithms are available, which have been tested on large numbers of physicians
      concerning the acceptance of such algorithms both by practicing clinical
      dermatologists and by their consulting specialists from other fields. OBJECTIVE:
      To propose a multidimensional assessment algorithm for psoriasis comorbidities
      which may prove at the same time enough sensitive and practically sustainable in
      daily clinical practice. METHODS: After an exhaustive literature search, we
      performed a Delphi procedure involving 50 dedicated dermatological centres to
      obtain a standardized assessment algorithm, which would meet requirements of
      sustainability and acceptability both from the point of view of Evidence-Based
      Medicine as well as from the point of view of practical and clinical feasibility:
      to meet both requirements, results from the Delphi procedure were elaborated and
      modified by a restricted panel of experts. RESULTS: The procedure has yielded
      PSOCUBE, a three-dimensional table comprising 14 clinical examination and history
      taking items, 32 screening laboratory and instrumental exams and 11 clinimetric
      scores. CONCLUSION: PSOCUBE, a simple algorithm, may be employed by practising
      dermatologists to perform standardized assessment procedures on psoriatic
      patients raising the chances of early recognition of patients at risk for
      comorbidities, thus fostering more effective prevention; PSOCUBE may therefore
      contribute to reduce the overall impact of this chronic, widespread disease.

PMID- 25370416
TI  - Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid
      disease progression.
AB  - Without effective therapy, chronic-phase chronic myeloid leukemia (CP-CML)
      evolves into an acute leukemia (blast crisis [BC]) that displays either myeloid
      or B-lymphoid characteristics. This transition is often preceded by a clinically
      recognized, but biologically poorly characterized, accelerated phase (AP). Here,
      we report that IKAROS protein is absent or reduced in bone marrow blasts from
      most CML patients with advanced myeloid disease (AP or BC). This contrasts with
      primitive CP-CML cells and BCR-ABL1-negative acute myeloid leukemia blasts, which
      express readily detectable IKAROS. To investigate whether loss of IKAROS
      contributes to myeloid disease progression in CP-CML, we examined the effects of
      forced expression of a dominant-negative isoform of IKAROS (IK6) in CP-CML
      patients' CD34(+) cells. We confirmed that IK6 disrupts IKAROS activity in
      transduced CP-CML cells and showed that it confers on them features of AP-CML,
      including a prolonged increased output in vitro and in xenografted mice of
      primitive cells with an enhanced ability to differentiate into basophils.
      Expression of IK6 in CD34(+) CP-CML cells also led to activation of signal
      transducer and activator of transcription 5 and transcriptional repression of its
      negative regulators. These findings implicate loss of IKAROS as a frequent step
      and potential diagnostic harbinger of progressive myeloid disease in CML
      patients. 

PMID- 25370417
TI  - EphB2 regulates contact-dependent and contact-independent signaling to control
      platelet function.
AB  - The Eph kinases, EphA4 and EphB1, and their ligand, ephrinB1, have been
      previously reported to be present in platelets where they contribute to thrombus
      stability. Although thrombus formation allows for Eph-ephrin engagement and
      bidirectional signaling, the importance specifically of Eph kinase or ephrin
      signaling in regulating platelet function remained unidentified. In the present
      study, a genetic approach was used in mice to establish the contribution of
      signaling orchestrated by the cytoplasmic domain of EphB2 (a newly discovered Eph
      kinase in platelets) in platelet activation and thrombus formation. We conclude
      that EphB2 signaling is involved in the regulation of thrombus formation and clot
      retraction. Furthermore, the cytoplasmic tail of this Eph kinase regulates
      initial platelet activation in a contact-independent manner in the absence of Eph
      ephrin ligation between platelets. Together, these data demonstrate that EphB2
      signaling not only modulates platelet function within a thrombus but is also
      involved in the regulation of the function of isolated platelets in a contact
      independent manner. 

PMID- 25370420
TI  - Double-blind peer review.

PMID- 25370418
TI  - Improvement of clinical quality indicators through reorganization of the acute
      care by establishing an emergency department-a register study based on data from
      national indicators.
AB  - BACKGROUND: The Emergency Departments (EDs) reorganization process in Denmark
      began in 2007 and includes creating a single entrance for all emergency patients,
      establishing triage, having a specialist in the front and introducing the use of
      electronic overview boards and electronic patient files. The aim of this study
      was to investigate the quality of acute care in a re-organized ED based on
      national indicator project data in a pre and post reorganizational setting.
      METHODS: Quasi experimental design was used to examine the effect of the health
      care quality in relation to the reorganization of an ED. Patients admitted at
      Nykobing Falster Hospital in 2008 or 2012 were included in the study and data
      reports from the national databases (RKKP) regarding stroke, COPD, heart failure,
      bleeding and perforated ulcer or hip fracture were analysed. Holbaek Hospital
      works as a control hospital. Chi-square test was used for analysing significant
      differences from pre-and post intervention and Z-test to compare the experimental
      groups to the control group (HOL). P < 0.05 was considered statistically
      significant. RESULTS: We assessed 4584 patient cases from RKKP. A significant
      positive change was seen in all of the additional eight indicators related to
      stroke at NFS (P < 0.001); however, COPD indicators were unchanged in both
      hospitals. In NFS two of eight heart failure indicators were significantly
      improved after the reorganization (p < 0.01). In patients admitted with a
      bleeding ulcer 2 of 5 indicators were significantly improved after the
      reorganization in NFS and HOL (p < 0.01). Both compared hospitals showed
      significant improvements in the two indicators concerning hip fracture (p <
      0.001). Significant reductions in the 30 day-mortality in patients admitted with
      stroke were seen when the pre- and the post-intervention data were compared for
      both NFS and HOL (p = 0.024). CONCLUSIONS: During the organisation of the new
      EDs, several of the indicators improved and the overall 30 days mortality
      decreased in the five diseases. The development of a common set of indicators for
      monitoring acute treatment at EDs in Denmark is recommended.

PMID- 25370419
TI  - Simultaneous sinus and lung infections in patients with primary ciliary
      dyskinesia.
AB  - CONCLUSION: The sinuses should be considered as a bacterial reservoir and a
      target for surgery and antibiotic treatment in patients with primary ciliary
      dyskinesia (PCD). The observed decrease in serum precipitating antibodies
      (precipitins) against Pseudomonas aeruginosa may indicate a beneficial effect of
      combined endoscopic sinus surgery (ESS) and concomitant medical treatment.
      OBJECTIVES: The purpose of this research, which is the first study addressing
      bacteriology in the sinuses of patients with PCD, was to examine the association
      between sinus and lung infections. METHODS: We reviewed findings of bacterial
      pathogens from the sinuses obtained during ESS and the lung infection status in
      eight PCD patients over a 6 year period. Precipitins against P. aeruginosa were
      used as a marker of severity of chronic infection and effect of treatment.
      RESULTS: Preoperatively, seven of the eight patients (88%) exhibited intermittent
      or chronic pulmonary infection with P. aeruginosa. Sinus cultures were obtained
      during ESS in seven patients. The sinuses were colonized with P. aeruginosa in
      four of seven patients (57%). Bacterial sinusitis was found in five of seven
      patients (71%) and the same bacterium was found in the sinuses and lungs in all
      cases. Decreasing precipitins against P. aeruginosa were observed postoperatively
      in three of four evaluable patients.

PMID- 25370421
TI  - Balancing scientific tensions.

PMID- 25370422
TI  - Double-blind under review.

PMID- 25370424
TI  - Drug delivery: replenishing reservoirs in vivo.

PMID- 25370425
TI  - Graphene nanoribbons: chemical stitching.

PMID- 25370426
TI  - Single-molecule junctions: thermoelectricity at the gate.

PMID- 25370427
TI  - Optomechanics: photons that pivot and shuttle.

PMID- 25370428
TI  - Nobel Prize in Chemistry: seeing the nanoscale.

PMID- 25370429
TI  - Nobel Prize in Physics: nitrides in the spotlight.

PMID- 25370430
TI  - Playing with a nanoscale see-saw.

PMID- 25370431
TI  - Liquid body formation from a semispherical superhydrophobic well on a small
      incline.
AB  - In this work, drop formation on a slightly inclined superhydrophobic substrate
      with liquid at various flow rates delivered through a semispherical well was
      investigated. Due to the initial dry well condition in the first drop produced,
      the inertial force from liquid filling allowed the well's edge hysteresis to be
      more readily breached, in which flow rates of 16 mL/min and above could create a
      jet that appeared to be able to "pierce" through the top of the semispherical
      drop without disrupting its form and growth very much. For subsequent drops, the
      well's edge hysteresis at flow rates of 14 mL/min and above helped to support an
      "egg" like form. In contrast, this form could not be developed on a similarly
      inclined superhydrophobic substrate without a well. The findings here assist to
      establish the flow rate ranges for consistent discrete volume delivery in
      biochemical analysis and serves as a means to conduct investigations to better
      reconcile the tendency of liquids to assume drops or develop jets. 

PMID- 25370432
TI  - Building healthy bones throughout life: an evidence-informed strategy to prevent
      osteoporosis in Australia.
AB  - Osteoporosis imposes a tremendous burden on Australia: 1.2 million Australians
      have osteoporosis and 6.3 million have osteopenia. In the 2007-08 financial year,
      82 000 Australians suffered fragility fractures, of which > 17 000 were hip
      fractures. In the 2000-01 financial year, direct costs were estimated at $1.9
      billion per year and an additional $5.6 billion on indirect costs. Osteoporosis
      was designated a National Health Priority Area in 2002; however, implementation
      of national plans has not yet matched the rhetoric in terms of urgency. Building
      healthy bones throughout life, the Osteoporosis Australia strategy to prevent
      osteoporosis throughout the life cycle, presents an evidence-informed set of
      recommendations for consumers, health care professionals and policymakers. The
      strategy was adopted by consensus at the Osteoporosis Australia Summit in Sydney,
      20 October 2011. Primary objectives throughout the life cycle are: to maximise
      peak bone mass during childhood and adolescence to prevent premature bone loss
      and improve or maintain muscle mass, strength and functional capacity in healthy
      adults to prevent and treat osteoporosis in order to minimise the risk of
      suffering fragility fractures, and reduce falls risk, in older people. The
      recommendations focus on three affordable and important interventions - to ensure
      people have adequate calcium intake, vitamin D levels and appropriate physical
      activity throughout their lives. Recommendations relevant to all stages of life
      include: daily dietary calcium intakes should be consistent with Australian and
      New Zealand guidelines serum levels of vitamin D in the general population should
      be above 50nmol/L in winter or early spring for optimal bone health regular
      weight-bearing physical activity, muscle strengthening exercises and challenging
      balance/mobility activities should be conducted in a safe environment.

PMID- 25370433
TI  - Psoriasis today: experiences of healthcare and impact on quality of life in a
      major UK cohort.
AB  - AIM: To establish how people with psoriasis in the United Kingdom today
      experience living with their condition including diagnosis, treatment, healthcare
      provision and impact on daily life. BACKGROUND: Psoriasis is a debilitating long
      term inflammatory skin disease which can result in severe itching, discomfort and
      soreness, and may be associated with problems beyond the specific symptoms
      related to the skin. For many it is accompanied by difficult-to-manage treatment
      regimes, emotional distress and a negative impact on their quality of life and
      psychosocial functioning. To date there is little published information about the
      health experiences of people in the United Kingdom with psoriasis. METHODS: A
      postal self-administered questionnaire was completed by members of the Psoriasis
      Association and the responses analysed (n = 1564). FINDINGS: The findings suggest
      some similarities to surveys in other nations, but specifically highlighted that
      patients feel under-informed and are dissatisfied with current treatment regimes.
      Responses provided an insight into aspects of the condition that treatments
      should be targeting. Specific areas of negative impact on psychosocial
      functioning were identified, including the lack of available support for those
      experiencing emotional distress. The research provides important information
      about how the care of patients with psoriasis can be improved, especially at
      primary care level. This includes: improved training in psoriasis knowledge and
      awareness at general practitioner level and greater use of dermatology specialist
      nurses in primary care settings; more effective and manageable treatment regimes
      that target visible areas and general well-being; greater support for emotional
      distress and psychosocial functioning.

PMID- 25370435
TI  - Albuminuria in prediabetes: time to intervene?

PMID- 25370434
TI  - Community-acquired meningitis in older adults: clinical features, etiology, and
      prognostic factors.
AB  - OBJECTIVES: To investigate the epidemiology and outcomes of community-acquired
      meningitis in older adults. DESIGN: Retrospective study. SETTING: Participants
      adults in Houston, Texas, with community-acquired meningitis hospitalized between
      January 1, 2005, and January 1, 2010 (N = 619; n = 54, 8.7%, aged >=65; n = 565
      aged <65). METHODS: An adverse clinical outcome was defined as a Glasgow Outcome
      Scale score of 4 or less. RESULTS: Older adults had higher rates of
      comorbidities, abnormal neurological and laboratory (serum white blood cell count
      >12,000/MUL, and cerebrospinal fluid protein >100 mg/dL) findings (P < .001),
      abnormalities on computed tomography and magnetic resonance imaging of the head
      (P = .002), and adverse clinical outcomes (ACOs) (P < .001). The majority of
      participants (65.8%) had meningitis of unknown etiology. Bacterial meningitis was
      an infrequent cause of community-acquired meningitis (7.4%). Of the known causes,
      bacterial meningitis and West Nile virus were more common in older than younger
      adults; younger participants more frequently had cryptococcal and viral
      meningitis. On logistic regression, female sex was predictive of a poor outcome
      in the older participants (P = .002), whereas abnormal neurological examination
      (P < .001), fever (P = .01), and a cerebrospinal fluid glucose level less than 45
      mg/dL (P = .002) were significant poor prognostic factors in younger
      participants. CONCLUSION: Most cases of community-acquired meningitis are of
      unknown origin. Older adults are more likely than younger adults to have
      bacterial meningitis and West Nile virus infection when a cause can be
      identified. They also have more neurological abnormalities, laboratory and
      imaging abnormalities, and adverse clinical outcomes.

PMID- 25370436
TI  - Suicidal Behavior Outcomes of Childhood Sexual Abuse: Longitudinal Study of
      Adjudicated Girls.
AB  - Childhood sexual abuse (CSA) histories are prevalent among adolescent girls in
      the juvenile justice system (JJS) and may contribute to their high rates of
      suicidal behavior. Among 166 JJS girls who participated in an intervention trial,
      baseline CSA and covariates were examined as predictors of suicide attempt and
      nonsuicidal self-injury (NSSI) reported at long-term follow-up (7-12 years
      later). Early forced CSA was related to lifetime suicide attempt and NSSI history
      and (marginally) to postbaseline attempt; effects were not mediated by anxiety or
      depressive symptoms. Findings suggest that earlier victimization and younger
      entry into JJS are linked with suicide attempt and NSSI. 

PMID- 25370438
TI  - Remembering Joshua B. Cantor, PhD.

PMID- 25370437
TI  - Usefulness of monitoring of B cell depletion in rituximab-treated rheumatoid
      arthritis patients in order to predict clinical relapse: a prospective
      observational study.
AB  - Our objective was to evaluate the contribution of monitoring B cell subset
      depletion after rituximab in patients with rheumatoid arthritis (RA) in order to
      guide reintroduction to forestall relapse. This prospective, monocentre study
      included all RA patients receiving two 1-g rituximab infusions at a 15-day
      interval. The patients were followed clinically and biologically every 2 months
      until rituximab reintroduction. The physician was blinded to lymphocyte-typing
      results to diagnose relapse and, hence, retreatment. Among the 39 patients
      included between March 2010 and December 2011 and followed until April 2013,
      seven received two rituximab cycles, yielding a total of 46 cycles for analysis.
      After the two rituximab cycles, the total number of CD19(+) B cells decreased
      significantly (0.155 versus 0.0002 G/l, P < 0.0001), with complete depletions in
      all patients of CD19(+) CD38(++) CD24(++) (transitional) (P < 0.0001) and CD19(+)
      CD27(+) (memory) B lymphocytes. A significant majority of patients relapsed
      within the 4 months following repopulation of total B (P = 0.036), B transitional
      (P = 0.007) and B memory (P = 0.01) lymphocytes. CD19(+) B lymphocyte
      repopulation preceded clinical RA relapse and enabled its prediction 4 months in
      advance. Hence, monitoring of CD19(+) B lymphocytes could serve as a tool to
      predict those relapses. 

PMID- 25370439
TI  - Comparison of cognitive behavioral therapy and supportive psychotherapy for the
      treatment of depression following traumatic brain injury: a randomized controlled
      trial.
AB  - OBJECTIVE: To determine the efficacy of 2 different interventions (cognitive
      behavioral therapy [CBT] and supportive psychotherapy [SPT]) to treat post
      traumatic brain injury (TBI) depression. PARTICIPANTS: A sample of 77 community
      dwelling individuals with a TBI, and a diagnosis of depression. Participants were
      randomized into treatment conditions either CBT or SPT and received up to 16
      sessions of individual psychotherapy. MEASURES: Participants completed the
      Structured Clinical Interview for DSM-IV and self-report measures of depression
      (Beck Depression Inventory-Second Edition), anxiety (State-Trait Anxiety
      Inventory), perceived social support (Interpersonal Support Evaluation List),
      stressful life events (Life Experiences Survey), and quality of life (QOL) before
      beginning and immediately following treatment. RESULTS: No significant
      differences were found at baseline between CBT and SPT groups on demographic
      factors (sex, age, education, race, and time since injury) or baseline measures
      of depression, anxiety, participation, perceived social support, stressful life
      events, or QOL. Analyses of variance revealed significant time effects for the
      Beck Depression Inventory-Second Edition, State-Trait Anxiety Inventory, and QOL
      outcome measures but no group effects. Intention-to-treat mixed effects analyses
      did not find any significant difference in patterns of scores of the outcome
      measures between the CBT and SPT intervention groups. CONCLUSIONS: Both forms of
      psychotherapy were efficacious in improving diagnoses of depression and anxiety
      and reducing depressive symptoms. These findings suggest that in this sample of
      individuals with TBI, CBT was not more effective in treating depression than SPT,
      though further research is needed with larger sample sizes to identify different
      components of these interventions that may be effective with different TBI
      populations. ClinicalTrials.gov Identifier: NCT00211835.

PMID- 25370441
TI  - Systematic review of interventions for fatigue after traumatic brain injury: a
      NIDRR traumatic brain injury model systems study.
AB  - OBJECTIVE: To conduct a systematic review of the evidence on interventions for
      posttraumatic brain injury fatigue (PTBIF). METHODS: Systematic searches of
      multiple databases for peer-reviewed studies published in English on
      interventions targeting PTBIF as a primary or secondary outcome through January
      22, 2014. Reference sections were also reviewed to identify additional articles.
      Articles were rated using the 2011 American Academy of Neurology Classification
      of Evidence Scheme for therapeutic studies. RESULTS: The searches yielded 1526
      articles. Nineteen articles met all inclusion criteria: 4 class I, 1 class
      II/III, 10 class III, and 4 class IV. Only 5 articles examined fatigue as a
      primary outcome. Interventions were pharmacological and psychological or involved
      physical activity, bright blue light, electroencephalographic biofeedback, or
      electrical stimulation. Only 2 interventions (modafinil and cognitive behavioral
      therapy with fatigue management) were evaluated in more than 1 study.
      CONCLUSIONS: Despite areas of promise, there is insufficient evidence to
      recommend or contraindicate any treatments of PTBIF. Modafinil is not likely to
      be effective for PTBIF. Piracetam may reduce it, as may bright blue light.
      Cognitive behavioral therapy deserves additional study. High-quality research
      incorporating appropriate definition and measurement of fatigue is required to
      explore the potential benefits of promising interventions, evaluate fatigue
      treatments shown to be effective in other populations, and develop new
      interventions for PTBIF.

PMID- 25370440
TI  - Screening for traumatic brain injury: findings and public health implications.
AB  - OBJECTIVE: To provide an overview of a series of projects that used a structured
      self-report screening tool in diverse settings and samples to screen for lifetime
      history of traumatic brain injury (TBI). SETTING: Diverse community settings.
      PARTICIPANTS: Homeless persons (n = 111), individuals with HIV seeking vocational
      rehabilitation (n = 173), youth in the juvenile justice system (n = 271), public
      schoolchildren (n = 174), substance users (n = 845), intercollegiate athletes (n
      = 90), and other community-based samples (n = 396). DESIGN: Cross-sectional. MAIN
      MEASURE: Brain Injury Screening Questionnaire. RESULTS: Screening using the Brain
      Injury Screening Questionnaire finds that 27% to 54% of those in high-risk
      populations report a history of TBI with chronic symptoms. Associations between
      TBI and social, academic, or other problems are evident in several studies. In
      non-high-risk community samples, 9% to 12% of individuals report TBI with chronic
      symptoms. CONCLUSION: Systematic TBI screening can be implemented efficiently and
      inexpensively in a variety of settings. Lifetime TBI history data gathered using
      a structured self-report instrument can augment existing estimates of the
      prevalence of TBI, both as an acute event and as a chronic condition.
      Identification of individuals with TBI can facilitate primary prevention efforts,
      such as reducing risk for reinjury in high-risk groups, and provide access to
      appropriate interventions that can reduce the personal and societal costs of TBI
      (tertiary prevention).

PMID- 25370444
TI  - Disparity in population structuring of Southwestern Willow Flycatchers based on
      geographic distance, movement patterns, and genetic analyses.
AB  - Estimates of population connectivity often are based on demographic analysis of
      movements among subpopulations, but this approach may fail to detect rare
      migrants or overestimate the contribution of movements into populations when
      migrants fail to successfully reproduce. We compared movement data of endangered
      Southwestern Willow Flycatchers among isolated populations in Nevada and Arizona
      from 1997 to 2008 to genetic analyses of samples collected between 2004 and 2008
      to determine the degree to which these two methods were concordant in their
      estimates of population structuring. Given that documented movements of 13 color
      banded adults and 23 juveniles over 10 years indicated low rates of long-distance
      movements, we predicted that genetic analyses would show significant population
      structuring between a northern (Nevada) deme and a southern (Arizona) deme. We
      genotyped 93 adult individuals at seven microsatellite loci and used two Bayesian
      clustering programs, STRUCTURE and GENELAND, to predict population structure.
      Both clustering algorithms produced the same structuring pattern; a cluster
      containing birds breeding in Pahranagat National Wildlife Refuge, the northern
      most Nevada site, and a cluster comprised of all other populations. These results
      highlight that estimates of subpopulation connectivity based on demographic
      analyses may differ from those based on genetics, suggesting either temporal
      changes in the pattern of movements, the importance of undetected movements, or
      differential contribution of migrants to the subpopulations they enter.

PMID- 25370442
TI  - Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in
      rats is region-specific and demonstrates limited efficacy of gabapentin.
AB  - Intractable central post-stroke pain (CPSP) is one of the most common sequelae of
      stroke, but has been inadequately studied to date. In this study, we first
      determined the relationship between the lesion site and changes in mechanical or
      thermal pain sensitivity in a rat CPSP model with experimental thalamic
      hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection.
      Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds
      the voltage-gated Ca(2+) channel alpha2delta and a commonly used anti-neuropathic
      pain medication. Histological case-by-case analysis showed that only lesions
      confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of
      the thalamus and/or the posterior thalamic nucleus resulted in bilateral
      mechanical pain hypersensitivity. All of the animals displaying CPSP also had
      impaired motor coordination, while control rats with intra-thalamic saline
      developed no central pain or motor deficits. GBP had a dose-related anti
      allodynic effect after a single administration (1, 10, or 100 mg/kg) on day 7
      post-ITC, with significant effects lasting at least 5 h for the higher doses.
      However, repeated treatment, once a day for two weeks, resulted in complete loss
      of effectiveness (drug tolerance) at 10 mg/kg, while effectiveness remained at
      100 mg/kg, although the time period of efficacious analgesia was reduced. In
      addition, GBP did not change the basal pain sensitivity and the motor impairment
      caused by the ITC lesion, suggesting selective action of GBP on the somatosensory
      system.

PMID- 25370443
TI  - Dysfunction of hippocampal interneurons in epilepsy.
AB  - Gamma-amino-butyric acid (GABA)-containing interneurons are crucial to both
      development and function of the brain. Down-regulation of GABAergic inhibition
      may result in the generation of epileptiform activity. Loss, axonal sprouting,
      and dysfunction of interneurons are regarded as mechanisms involved in
      epileptogenesis. Recent evidence suggests that network connectivity and the
      properties of interneurons are responsible for excitatory-inhibitory neuronal
      circuits. The balance between excitation and inhibition in CA1 neuronal circuitry
      is considerably altered during epileptic changes. This review discusses
      interneuron diversity, the causes of interneuron dysfunction in epilepsy, and the
      possibility of using GABAergic neuronal progenitors for the treatment of
      epilepsy. 

PMID- 25370446
TI  - Crystal structure of lambda exonuclease in complex with DNA and Ca(2+).
AB  - Bacteriophage lambda exonuclease (lambdaexo) is a ring-shaped homotrimer that
      resects double-stranded DNA ends in the 5'-3' direction to generate a long 3'
      overhang that is a substrate for recombination. lambdaexo is a member of the type
      II restriction endonuclease-like superfamily of proteins that use a Mg(2+)
      dependent mechanism for nucleotide cleavage. A previous structure of lambdaexo in
      complex with DNA and Mg(2+) was determined using a nuclease defective K131A
      variant to trap a stable complex. This structure revealed the detailed
      coordination of the two active site Mg(2+) ions but did not show the interactions
      involving the side chain of the conserved active site Lys-131 residue. Here, we
      have determined the crystal structure of wild-type (WT) lambdaexo in complex with
      the same DNA substrate, but in the presence of Ca(2+) instead of Mg(2+).
      Surprisingly, there is only one Ca(2+) bound in the active site, near the
      position of Mg(A) in the structure with Mg(2+). The scissile phosphate is
      displaced by 2.2 A relative to its position in the structure with Mg(2+), and the
      network of interactions involving the attacking water molecule is broken. Thus,
      the structure does not represent a catalytic configuration. However, the crystal
      structure does show clear electron density for the side chain of Lys-131, which
      is held in place by interactions with Gln-157 and Glu-129. By combining the K131A
      Mg(2+) and WT-Ca(2+) structures, we constructed a composite model to show the
      likely interactions of Lys-131 during catalysis. The implications with regard to
      the catalytic mechanism are discussed. 

PMID- 25370445
TI  - Irreversible covalent modification of type I dehydroquinase with a stable Schiff
      base.
AB  - The irreversible inhibition of type I dehydroquinase (DHQ1), the third enzyme of
      the shikimic acid pathway, is investigated by structural, biochemical and
      computational studies. Two epoxides, which are mimetics of the natural substrate,
      were designed as irreversible inhibitors of the DHQ1 enzyme and to study the
      binding requirements of the linkage to the enzyme. The epoxide with the S
      configuration caused the covalent modification of the protein whereas no reaction
      was obtained with its epimer. The first crystal structure of DHQ1 from Salmonella
      typhi covalently modified by the S epoxide, which is reported at 1.4 A, revealed
      that the modified ligand is surprisingly covalently attached to the essential
      Lys170 by the formation of a stable Schiff base. The experimental and molecular
      dynamics simulation studies reported here highlight the huge importance of the
      conformation of the C3 carbon of the ligand for covalent linkage to this type of
      aldolase I enzyme, revealed the key role played by the essential His143 as a
      Lewis acid in this process and show the need for a neatly closed active site for
      catalysis. 

PMID- 25370447
TI  - Frequency-controls of electromagnetic multi-beam scanning by metasurfaces.
AB  - We propose a method to control electromagnetic (EM) radiations by holographic
      metasurfaces, including to producing multi-beam scanning in one dimension (1D)
      and two dimensions (2D) with the change of frequency. The metasurfaces are
      composed of subwavelength metallic patches on grounded dielectric substrate. We
      present a combined theory of holography and leaky wave to realize the multi-beam
      radiations by exciting the surface interference patterns, which are generated by
      interference between the excitation source and required radiation waves. As the
      frequency changes, we show that the main lobes of EM radiation beams could
      accomplish 1D or 2D scans regularly by using the proposed holographic
      metasurfaces shaped with different interference patterns. This is the first time
      to realize 2D scans of antennas by changing the frequency. Full-wave simulations
      and experimental results validate the proposed theory and confirm the
      corresponding physical phenomena. 

PMID- 25370448
TI  - A retrospective survey of ocular abnormalities in pugs: 130 cases.
AB  - OBJECTIVES: To determine the types and frequency of ophthalmic findings in pugs.
      MATERIALS AND METHODS: Retrospective analysis of case records of pugs presented
      to an ophthalmology unit between 2001 and 2012. Ophthalmological findings were
      correlated with age, gender, presenting signs and time of onset of disease.
      RESULTS: In total, 130 pugs (258 eyes) with a mean (+/-sd) age of 2 . 8 (+/-2 .
      87) years were examined. Ocular abnormalities identified included
      keratoconjunctivitis sicca (n = 39 eyes), macroblepharon (n = 258 eyes),
      entropion (n = 258 eyes), distichiasis (n = 56 eyes), ectopic cilia (n = 8 eyes),
      conjunctivitis (n = 88 eyes), corneal pigmentation (n = 101 eyes), opacity (n =
      63 eyes), ulceration (n = 46 eyes), vascularisation (n = 35 eyes), iris-to-iris
      persistent pupillary membranes (n = 21 eyes) and cataract (n = 18).
      Keratoconjunctivitis sicca was significantly associated with the presence of
      corneal pigmentation (P = 0 . 007 for left eyes; P = 0 . 043 for right eyes).
      However corneal pigmentation was also identified in pugs (n = 61) without
      keratoconjunctivitis sicca. There was a significant influence of ectopic cilia on
      corneal ulceration (P < 0 . 001). Younger dogs (mean age, 1 . 28 (+/-0 . 45)
      years) were significantly more affected by distichiasis. CLINICAL SIGNIFICANCE:
      The high number of cases of corneal pigmentation without keratoconjunctivitis
      sicca suggests that there may be additional yet undetermined factors involved in
      the development of corneal pigmentation in pugs.

PMID- 25370449
TI  - Surface roughness dependent osteoblast and fibroblast response on poly(L-lactide)
      films and electrospun membranes.
AB  - Poly(l-lactide) electrospun mats with random and aligned fiber orientation and
      films have been produced with degrees of crystallinity ranging from 0 up to
      nearly 50%. The overall surface roughness is practically constant irrespective of
      the sampling areas (1 * 1 um to 20 * 20 um) for degrees of crystallinity below
      30%, increasing for higher degrees of crystallinity for the larger sampling
      areas. Further, due to fiber confinement, surface roughness variations are
      smaller in electrospun mats. Samples with 50% of crystallinity show the lowest
      osteoblast and the highest fibroblast proliferation. Therefore, it is verified
      that higher roughness promotes lower osteoblast but higher fibroblast
      proliferation. The overall results indicate the relevant role of the sub
      microenvironment variations associated to the microscale roughness in determining
      the different cell responses.

PMID- 25370450
TI  - Concluding remarks: there's nowt so queer as carbon electrodes.
AB  - This contribution provides a personal overview and summary of Faraday Discussion
      172 on "Carbon in Electrochemistry", covering some of the key points made at the
      meeting within the broader context of other recent developments on carbon
      materials for electrochemical applications. Although carbon electrodes have a
      long history of use in electrochemistry, methods and techniques are only just
      becoming available that can test long-established models and identify key
      features for further exploration. This Discussion has highlighted the need for a
      better understanding of the impact of surface structure, defects, local density
      of electronic states, and surface functionality and contamination, in order to
      advance fundamental knowledge of various electrochemical processes and phenomena
      at carbon electrodes. These developments cut across important materials such as
      graphene, carbon nanotubes, conducting diamond and high surface area carbon
      materials. With more detailed pictures of structural and electronic controls of
      electrochemistry at carbon electrodes (and electrodes generally), will come
      rational advances in various technological applications, from sensors to energy
      technology (particularly batteries, supercapacitors and fuel cells), that have
      been well-illustrated at this Discussion. 

PMID- 25370451
TI  - A case of severe ventricular arrhythmias occurring as a complication of nerve
      stimulator guided brachial plexus location.

PMID- 25370452
TI  - Heterogeneity of neural mechanisms of response to pivotal response treatment.
AB  - We investigated the mechanisms by which Pivotal Response Treatment (PRT) improves
      social communication in a case series of 10 preschool-aged children with Autism
      Spectrum Disorder (ASD). Functional magnetic resonance imaging (fMRI) identified
      brain responses during a biological motion perception task conducted prior to and
      following 16 weeks of PRT treatment. Overall, the neural systems supporting
      social perception in these 10 children were malleable through implementation of
      PRT; following treatment, neural responses were more similar to those of
      typically developing children (TD). However, at baseline, half of the children
      exhibited hypoactivation, relative to a group of TD children, in the right
      posterior superior temporal sulcus (pSTS), and half exhibited hyperactivation in
      this region. Strikingly, the groups exhibited differential neural responses to
      treatment: The five children who exhibited hypoactivation at baseline evidenced
      increased activation in components of the reward system including the ventral
      striatum and putamen. The five children who exhibited hyperactivation at baseline
      evidenced decreased activation in subcortical regions critical for regulating the
      flow of stimulation and conveying signals of salience to the cortex-the thalamus,
      amygdala, and hippocampus. Our results support further investigation into the
      differential effects of particular treatment strategies relative to specific
      neural targets. Identification of treatment strategies that address the patterns
      of neural vulnerability unique to each patient is consistent with the priority of
      creating individually tailored interventions customized to the behavioral and
      neural characteristics of a given person. 

PMID- 25370453
TI  - PharmGKB summary: very important pharmacogene information for CYP4F2.

PMID- 25370454
TI  - Metformin decreases IL-22 secretion to suppress tumor growth in an orthotopic
      mouse model of hepatocellular carcinoma.
AB  - Epidemiological, preclinical and cellular studies in the last 5 years have shown
      that metformin exerts anti-tumoral properties, but its mode of action in cancer
      remains unclear. Here, we investigated the effects of metformin on a mouse
      hepatocellular carcinoma (HCC) model and tumor-associated T cell immune
      responses. Oral metformin administration led to a significant reduction of tumor
      growth, which was accompanied by decreased interleukin-22 (IL-22). Meanwhile, IL
      22-induced STAT3 phosphorylation and upregulation of downstream genes Bcl-2 and
      cyclin D1 were inhibited by metformin. At the cellular level, metformin
      attenuated Th1- and Th17-derived IL-22 production. Furthermore, metformin
      inhibited de novo generation of Th1 and Th17 cells from naive CD4(+) cells. These
      observations were further supported by the fact that metformin treatment
      inhibited CD3/CD28-induced IFN-gamma and IL-17A expression along with the
      transcription factors that drive their expression (T-bet [Th1] and ROR-gammat
      [Th17], respectively). The effects of metformin on T cell differentiation were
      mediated by downregulated STAT3 and STAT4 phosphorylation via the AMP-activated
      kinase-mammalian target of rapamycin complex 1 pathway. Notably, metformin led to
      a reduction in glucose transporter Glut1 expression, resulting in less glucose
      uptake, which is critical to regulate CD4(+) T cell fate. Taken together, these
      findings provide evidence for the growth-inhibitory and immune-modulatory effects
      of metformin in HCC and thus, broaden our understanding about the action of
      metformin in liver cancer treatment. 

PMID- 25370455
TI  - Expression of the heparan sulfate 6-O-endosulfatases, Sulf1 and Sulf2, in the
      avian and mammalian inner ear suggests a role for sulfation during inner ear
      development.
AB  - BACKGROUND: Inner ear morphogenesis is tightly regulated by the temporally and
      spatially coordinated action of signaling ligands and their receptors. Ligand
      receptor interactions are influenced by heparan sulfate proteoglycans (HSPGs),
      cell surface molecules that consist of glycosaminoglycan chains bound to a
      protein core. Diversity in the sulfation pattern within glycosaminoglycan chains
      creates binding sites for numerous cell signaling factors, whose activities and
      distribution are modified by their association with HSPGs. RESULTS: Here we
      describe the expression patterns of two extracellular 6-O-endosulfatases, Sulf1
      and Sulf2, whose activity modifies the 6-O-sulfation pattern of HSPGs. We use in
      situ hybridization to determine the temporal and spatial distribution of
      transcripts during the development of the chick and mouse inner ear. We also use
      immunocytochemistry to determine the cellular localization of Sulf1 and Sulf2
      within the sensory epithelia. Furthermore, we analyze the organ of Corti in
      Sulf1/Sulf2 double knockout mice and describe an increase in the number of
      mechanosensory hair cells. CONCLUSIONS: Our results suggest that the tuning of
      intracellular signaling, mediated by Sulf activity, plays an important role in
      the development of the inner ear.

PMID- 25370456
TI  - Nutrition and metabolism.

PMID- 25370457
TI  - Microsomal triglyceride transfer protein inhibition: a novel treatment for
      lowering plasma cholesterol.

PMID- 25370458
TI  - Cardiovascular epigenome-wide association studies: is epigenetics falling short?

PMID- 25370460
TI  - Ecotypes of an ecologically dominant prairie grass (Andropogon gerardii) exhibit
      genetic divergence across the U.S. Midwest grasslands' environmental gradient.
AB  - Big bluestem (Andropogon gerardii) is an ecologically dominant grass with wide
      distribution across the environmental gradient of U.S. Midwest grasslands. This
      system offers an ideal natural laboratory to study population divergence and
      adaptation in spatially varying climates. Objectives were to: (i) characterize
      neutral genetic diversity and structure within and among three regional ecotypes
      derived from 11 prairies across the U.S. Midwest environmental gradient, (ii)
      distinguish between the relative roles of isolation by distance (IBD) vs.
      isolation by environment (IBE) on ecotype divergence, (iii) identify outlier loci
      under selection and (iv) assess the association between outlier loci and climate.
      Using two primer sets, we genotyped 378 plants at 384 polymorphic AFLP loci
      across regional ecotypes from central and eastern Kansas and Illinois. Neighbour
      joining tree and PCoA revealed strong genetic differentiation between Kansas and
      Illinois ecotypes, which was better explained by IBE than IBD. We found high
      genetic variability within prairies (80%) and even fragmented Illinois prairies,
      surprisingly, contained high within-prairie genetic diversity (92%). Using
      Bayenv2, 14 top-ranked outlier loci among ecotypes were associated with
      temperature and precipitation variables. Six of seven BayeScanFST outliers were
      in common with Bayenv2 outliers. High genetic diversity may enable big bluestem
      populations to better withstand changing climates; however, population divergence
      supports the use of local ecotypes in grassland restoration. Knowledge of genetic
      variation in this ecological dominant and other grassland species will be
      critical to understanding grassland response and restoration challenges in the
      face of a changing climate.

PMID- 25370461
TI  - Alternaria arborescens infection in a healthy individual and literature review of
      cutaneous alternariosis.
AB  - A 28-year-old man presented at our clinic with 1-month history of an ulcer
      covered with crust on his left anterior tibia. Based on the morphological
      features and molecular identification, the patient was diagnosed as cutaneous
      alternariosis caused by Alternaria arborescens. He was successfully cured by oral
      itraconazole and topical use of 0.25% liposomal amphotericin B. A review of
      published studies revealed 29 cases of cutaneous alternariosis. Most cases (90%)
      occurred in immunosuppressed patients; itraconazole (59%) and voriconazole (24%)
      are the most effective treatments of choices.

PMID- 25370462
TI  - Bifunctional submicron colloidosomes coassembled from fluorescent and
      superparamagnetic nanoparticles.
AB  - Colloidosomes are microcapsules consisting of nanoparticle shells. These
      microcarriers can be self-assembled from a wide range of colloidal particles with
      selective chemical, physical, and morphological properties and show promise for
      application in the field of theranostic nanomedicine. Previous studies have
      mainly focused on fairly large colloidosomes (>1 MUm) based on a single kind of
      particle; however, the intrinsic building-block nature of this microcarrier has
      not been exploited so far for the introduction of tailored functionality at the
      nanoscale. We report a synthetic route based on interfacial shear rheology
      studies that allows the simultaneous incorporation of different nanoparticles
      with distinct physical properties, that is, superparamagnetic iron oxide and
      fluorescent silica nanoparticles, in a single submicron colloidosome. These
      tailor-made microcapsules can potentially be used in various biomedical
      applications, including magnetic hyperthermia, magnetic particle imaging, drug
      targeting, and bioimaging. 

PMID- 25370463
TI  - Finding collaborators: toward interactive discovery tools for research network
      systems.
AB  - BACKGROUND: Research networking systems hold great promise for helping biomedical
      scientists identify collaborators with the expertise needed to build
      interdisciplinary teams. Although efforts to date have focused primarily on
      collecting and aggregating information, less attention has been paid to the
      design of end-user tools for using these collections to identify collaborators.
      To be effective, collaborator search tools must provide researchers with easy
      access to information relevant to their collaboration needs. OBJECTIVE: The aim
      was to study user requirements and preferences for research networking system
      collaborator search tools and to design and evaluate a functional prototype.
      METHODS: Paper prototypes exploring possible interface designs were presented to
      18 participants in semistructured interviews aimed at eliciting collaborator
      search needs. Interview data were coded and analyzed to identify recurrent themes
      and related software requirements. Analysis results and elements from paper
      prototypes were used to design a Web-based prototype using the D3 JavaScript
      library and VIVO data. Preliminary usability studies asked 20 participants to use
      the tool and to provide feedback through semistructured interviews and completion
      of the System Usability Scale (SUS). RESULTS: Initial interviews identified
      consensus regarding several novel requirements for collaborator search tools,
      including chronological display of publication and research funding information,
      the need for conjunctive keyword searches, and tools for tracking candidate
      collaborators. Participant responses were positive (SUS score: mean 76.4%, SD
      13.9). Opportunities for improving the interface design were identified.
      CONCLUSIONS: Interactive, timeline-based displays that support comparison of
      researcher productivity in funding and publication have the potential to
      effectively support searching for collaborators. Further refinement and
      longitudinal studies may be needed to better understand the implications of
      collaborator search tools for researcher workflows.

PMID- 25370464
TI  - Phase I Study to Assess the Combination of Afatinib with Trastuzumab in Patients
      with Advanced or Metastatic HER2-Positive Breast Cancer.
AB  - PURPOSE: The HER2 mAb, trastuzumab, is a standard therapy for patients with HER2
      positive breast cancer before acquired resistance. Afatinib, an irreversible,
      oral, small-molecule ErbB family blocker, shows clinical activity in trastuzumab
      refractory HER2-positive breast cancer. EXPERIMENTAL DESIGN: This phase I study
      used a 3+3 dose escalation to determine the MTD of oral once-daily afatinib in
      combination with the recommended dose of intravenous trastuzumab (4 mg/kg week 1;
      2 mg/kg/wk thereafter). Adult women with confirmed advanced/metastatic HER2
      positive breast cancer were eligible. RESULTS: Of 18 patients treated, 16
      received daily afatinib 20 mg and two 30 mg. Overall, 4 of 13 and 2 of 2 patients
      receiving afatinib 20 mg and 30 mg, respectively, experienced dose-limiting
      toxicity (DLT; all CTCAE grade 3 diarrhea). Most frequent treatment-related
      adverse events were diarrhea (94%), rash (56%), and fatigue (56%). Overall,
      pharmacokinetic profiles of afatinib and trastuzumab in combination were
      consistent with the known characteristics of each alone. Overall, objective
      response and disease control rates were 11% and 39%, respectively, with median
      progression-free survival 111.0 days (95% confidence interval, 56.0-274.0).
      CONCLUSIONS: The MTD of afatinib was 20 mg daily combined with the recommended
      weekly dose of trastuzumab, with 1 of 6 patients showing DLTs in the dose
      escalation. However, additional DLTs occurred in the dose-expansion phase meaning
      that this MTD cannot be recommended for phase II development without strict
      diarrhea management. There was no evidence suggesting relevant pharmacokinetic
      drug-drug interactions. Signs of clinical activity were seen in trastuzumab
      resistant HER2-positive breast cancer, suggesting further investigation with
      optimal diarrhea management is warranted.

PMID- 25370465
TI  - Cytotoxicity of human endogenous retrovirus K-specific T cells toward autologous
      ovarian cancer cells.
AB  - PURPOSE: To determine whether HERV-K envelope (ENV) protein could function as a
      tumor-associated antigen and elicit specific T-cell responses against autologous
      ovarian cancer cells. EXPERIMENTAL DESIGN: The expression of HERV-K transcripts
      and ENV protein, the presence of serum antibodies against HERV-K, reverse
      transcriptase (RT) activities, and cellular immune responses in primary ovarian
      cancer tissues and patient blood samples were analyzed and compared with samples
      from patients with benign ovarian diseases and normal female donors. RESULTS:
      Ovarian cancer cells in primary tumors and ascites expressed markers of cancer
      stem cells and markers of both mesenchymal and epithelial cells. Expression of
      HERV transcripts and HERV-K ENV protein and reverse transcriptase activities were
      higher in ovarian cancer compared with adjacent normal and benign tissues. The
      ovarian cancer patient plasma also had high reverse transcriptase activities and
      the ovarian cancer patient sera contained HERV-K immunoreactive antibodies. HERV
      K-specific T cells generated from autologous dendritic cells pulsed with HERV-K
      ENV antigens exhibited phenotypes and functions consistent with a cellular immune
      response including T-cell proliferation, IFNgamma production, and HERV-K-specific
      cytotoxic T lymphocyte (CTL) activity. Significantly higher CTL lysis of
      autologous tumor cells than of uninvolved normal cells was demonstrated in
      patients with ovarian cancer than patients with benign diseases and further
      enhanced lysis was observed if T regulatory cells were depleted. CONCLUSION:
      Endogenous retroviral gene products in ovarian cancer may represent a potentially
      valuable new pool of tumor-associated antigens for targeting of therapeutic
      vaccines to ovarian cancer. Clin Cancer Res; 21(2); 471-83. (c)2014 AACR.

PMID- 25370466
TI  - Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI
      Cancer Cachexia.
AB  - PURPOSE: Skeletal muscle wasting and weight loss are characteristic features of
      cancer cachexia and contribute to impaired function, increased morbidity, and
      poor tolerance of chemotherapy. This study used a novel technique to measure
      habitual myofibrillar protein synthesis in patients with cancer compared with
      healthy controls. EXPERIMENTAL DESIGN: An oral heavy water (87.5 g deuterium
      oxide) tracer was administered as a single dose. Serum samples were taken over
      the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment
      was measured in body water, serum alanine, and alanine in the myofibrillar
      component of muscle using gas chromatography-pyrolysis-isotope ratio mass
      spectrometry and the protein synthesis rate calculated from the rate of tracer
      incorporation. Net change in muscle mass over the preceding 3 months was
      calculated from serial CT scans and allowed estimation of protein breakdown.
      RESULTS: Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (>=5%
      weight loss) patients undergoing surgery for upper gastrointestinal cancer were
      recruited. Serial CT scans were available in 10 patients, who lost skeletal
      muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein
      fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight
      stable, and weight-losing patients, respectively. Weight-losing patients had
      higher synthetic rates than controls (P = 0.03). CONCLUSION: Contrary to previous
      studies, there was no evidence of suppression of myofibrillar protein synthesis
      in patients with cancer cachexia. Our finding implies a small increase in muscle
      breakdown may account for muscle wasting.

PMID- 25370467
TI  - A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children
      and adolescents with solid tumors: a Cancer Research UK study.
AB  - PURPOSE: A phase I trial of AT9283 (a multitargeted inhibitor of Aurora kinases A
      and B) was conducted in children and adolescents with solid tumors, to identify
      maximum-tolerated dose (MTD), safety, efficacy, pharmacokinetics, and
      pharmacodynamic (PD) activity. EXPERIMENTAL DESIGN: AT9283 was administered as a
      72-hour continuous intravenous infusion every 3 weeks. A rolling-six design,
      explored six dose levels (7, 9, 11.5, 14.5, 18.5, and 23 mg/m(2)/d).
      Pharmacokinetic and PD assessments, included inhibition of phospho-histone 3
      (pHH3) in paired skin punch biopsies. RESULTS: Thirty-three patients were
      evaluable for toxicity. There were six dose-limiting toxicities and the MTD was
      18.5 mg/m(2)/d. Most common drug-related toxicities were hematologic
      (neutropenia, anemia, and thrombocytopenia in 36.4%, 18.2%, and 21.2% of
      patients), which were grade >=3 in 30.3%, 6.1%, and 3% of patients.
      Nonhematologic toxicities included fatigue, infections, febrile neutropenia and
      ALT elevation. One patient with central nervous system-primitive neuroectodermal
      tumor (CNS-PNET) achieved a partial response after 16 cycles and 3 cases were
      stable for four or more cycles. Plasma concentrations were comparable with those
      in adults at the same dose level, clearance was similar although half-life was
      shorter (4.9 +/- 1.5 hours, compared with 8.4 +/- 3.7 hours in adults).
      Inhibition of Aurora kinase B was shown by reduction in pHH3 in 17 of 18 patients
      treated at >=11.5 mg/m(2)/d. CONCLUSION: AT9283 was well tolerated in children
      and adolescents with solid tumors with manageable hematologic toxicity. Target
      inhibition was demonstrated. Disease stabilization was documented in intracranial
      and extracranial pediatric solid tumors and a phase II dose determined.

PMID- 25370468
TI  - Metabolic imaging of pancreatic ductal adenocarcinoma detects altered choline
      metabolism.
AB  - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal
      disease that develops relatively symptom-free and is therefore advanced at the
      time of diagnosis. The absence of early symptoms and effective treatments has
      created a critical need for identifying and developing new noninvasive biomarkers
      and therapeutic targets. EXPERIMENTAL DESIGN: We investigated the metabolism of a
      panel of PDAC cell lines in culture and noninvasively in vivo with (1)H magnetic
      resonance spectroscopic imaging (MRSI) to identify noninvasive biomarkers and
      uncover potential metabolic targets. RESULTS: We observed elevated choline
      containing compounds in the PDAC cell lines and tumors. These elevated choline
      containing compounds were easily detected by increased total choline (tCho) in
      vivo, in spectroscopic images obtained from tumors. Principal component analysis
      of the spectral data identified additional differences in metabolites between
      immortalized human pancreatic cells and neoplastic PDAC cells. Molecular
      characterization revealed overexpression of choline kinase (Chk)-alpha, choline
      transporter 1 (CHT1), and choline transporter-like protein 1 (CTL1) in the PDAC
      cell lines and tumors. CONCLUSIONS: Collectively, these data identify new
      metabolic characteristics of PDAC and reveal potential metabolic targets. Total
      choline detected with (1)H MRSI may provide an intrinsic, imaging probe
      independent biomarker to complement existing techniques in detecting PDAC. The
      expression of Chk-alpha, CHT1, and CTL1 may provide additional molecular markers
      in aspirated cytological samples.

PMID- 25370469
TI  - A novel MAPK-microRNA signature is predictive of hormone-therapy resistance and
      poor outcome in ER-positive breast cancer.
AB  - PURPOSE: Hyperactivation of ERK1/2 MAPK (hMAPK) leads to loss of estrogen
      receptor (ER) expression and poor outcome in breast cancer. microRNAs (miRNA)
      play important regulatory roles and serve as biomarkers of disease. Here, we
      describe molecular, pathologic, and clinical outcome associations of an hMAPK
      miRNA expression signature in breast cancer. EXPERIMENTAL DESIGN: An hMAPK-miRNA
      signature was identified, and associations of this signature with molecular and
      genetic alterations, gene expression, pathologic features, and clinical outcomes
      were determined in primary breast cancers from training data and validated using
      independent datasets. Univariate and multivariate analyses identified
      subsignatures associated with increased disease recurrence and poorer disease
      survival among ER-positive (ER(+)) patients, respectively. RESULTS: High-hMAPK
      miRNA status significantly correlated with ER-negativity, enrichment for basal
      and HER2-subtypes, and reduced recurrence-free and disease-specific survival in
      publicly available datasets. A robust determination of a recurrence signature and
      a survival signature identified hMAPK-miRNAs commonly associated with poor
      clinical outcome, and specific subsets associated more closely with either
      disease recurrence or disease survival, especially among ER(+) cancers of both
      luminal A and luminal B subtypes. Multivariate analyses indicated that these
      recurrence and survival signatures significantly associated with increased risk
      of disease-specific death and disease recurrence in ER(+) cancer and ER(+)
      cancers treated with hormone therapy. CONCLUSIONS: We report an hMAPK-miRNA
      signature and two subsignatures derived from it that associate significantly with
      adverse clinical features, poor clinical outcome, and poor response to hormone
      therapy in breast cancer, thus identifying potential effectors of MAPK signaling,
      and novel predictive and prognostic biomarkers or therapeutic targets in breast
      cancer.

PMID- 25370470
TI  - Potential mechanisms for thrombocytopenia development with trastuzumab emtansine
      (T-DM1).
AB  - PURPOSE: Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC)
      comprising the cytotoxic agent DM1 conjugated to trastuzumab with a stable
      linker. Thrombocytopenia was the dose-limiting toxicity in the phase I study, and
      grade >=3 thrombocytopenia occurred in up to 13% of patients receiving T-DM1 in
      phase III studies. We investigated the mechanism of T-DM1-induced
      thrombocytopenia. EXPERIMENTAL DESIGN: The effect of T-DM1 on platelet function
      was measured by aggregometry, and by flow cytometry to detect the markers of
      activation. The effect of T-DM1 on differentiation and maturation of
      megakaryocytes (MK) from human hematopoietic stem cells was assessed by flow
      cytometry and microscopy. Binding, uptake, and catabolism of T-DM1 in MKs, were
      assessed by various techniques including fluorescence microscopy, scintigraphy to
      detect T-[H(3)]-DM1 and (125)I-T-DM1, and mass spectrometry. The role of
      FcgammaRIIa was assessed using blocking antibodies and mutant constructs of
      trastuzumab that do not bind FcgammaR. RESULTS: T-DM1 had no direct effect on
      platelet activation and aggregation, but it did markedly inhibit MK
      differentiation via a cytotoxic effect. Inhibition occurred with DM1-containing
      ADCs but not with trastuzumab demonstrating a role for DM1. MKs internalized
      these ADCs in a HER2-independent, FcgammaRIIa-dependent manner, resulting in
      intracellular release of DM1. Binding and internalization of T-DM1 diminished as
      MKs matured; however, prolonged exposure of mature MKs to T-DM1 resulted in a
      disrupted cytoskeletal structure. CONCLUSIONS: These data support the hypothesis
      that T-DM1-induced thrombocytopenia is mediated in large part by DM1-induced
      impairment of MK differentiation, with a less pronounced effect on mature MKs.

PMID- 25370472
TI  - Livin contributes to tumor hypoxia-induced resistance to cytotoxic therapies in
      glioblastoma multiforme.
AB  - PURPOSE: Tumor hypoxia is one of the crucial microenvironments to promote therapy
      resistance (TR) in glioblastoma multiforme (GBM). Livin, a member of the family
      of inhibitor of apoptosis proteins, contributes antiapoptosis. However, the role
      of tumor hypoxia in Livin regulation and its impact on TR are unclear.
      EXPERIMENTAL DESIGN: Livin expression and apoptosis for tumor hypoxic cells
      derived from human glioblastoma xenografts or in vitro hypoxic stress-treated
      glioblastoma cells were determined by Western blotting, immunofluorescence
      imaging, and annexin V staining assay. The mechanism of hypoxia-induced Livin
      induction was investigated by chromatin immunoprecipitation assay and reporter
      assay. Genetic and pharmacologic manipulation of Livin was utilized to
      investigate the role of Livin on tumor hypoxia-induced TR in vitro or in vivo.
      RESULTS: The upregulation of Livin expression and downregulation of caspase
      activity were observed under cycling and chronic hypoxia in glioblastoma cells
      and xenografts, concomitant with increased TR to ionizing radiation and
      temozolomide. However, knockdown of Livin inhibited these effects. Moreover,
      hypoxia activated Livin transcription through the binding of hypoxia-inducible
      factor-1alpha to the Livin promoter. The targeted inhibition of Livin by the cell
      permeable peptide (TAT-Lp15) in intracerebral glioblastoma-bearing mice
      demonstrated a synergistic suppression of tumor growth and increased the survival
      rate in standard-of-care treatment with radiation plus temozolomide. CONCLUSIONS:
      These findings indicate a novel pathway that links upregulation of Livin to tumor
      hypoxia-induced TR in GBM and suggest that targeting Livin using cell-permeable
      peptide may be an effective therapeutic strategy for tumor microenvironment
      induced TR.

PMID- 25370471
TI  - First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I
      phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid
      tumors.
AB  - PURPOSE: This first-in-human dose-escalation trial evaluated the safety,
      tolerability, maximal-tolerated dose (MTD), dose-limiting toxicities (DLT),
      pharmacokinetics, pharmacodynamics, and preliminary clinical activity of
      pictilisib (GDC-0941), an oral, potent, and selective inhibitor of the class I
      phosphatidylinositol-3-kinases (PI3K). PATIENTS AND METHODS: Sixty patients with
      solid tumors received pictilisib at 14 dose levels from 15 to 450 mg once-daily,
      initially on days 1 to 21 every 28 days and later, using continuous dosing for
      selected dose levels. Pharmacodynamic studies incorporated (18)F-FDG-PET, and
      assessment of phosphorylated AKT and S6 ribosomal protein in platelet-rich plasma
      (PRP) and tumor tissue. RESULTS: Pictilisib was well tolerated. The most common
      toxicities were grade 1-2 nausea, rash, and fatigue, whereas the DLT was grade 3
      maculopapular rash (450 mg, 2 of 3 patients; 330 mg, 1 of 7 patients). The
      pharmacokinetic profile was dose-proportional and supported once-daily dosing.
      Levels of phosphorylated serine-473 AKT were suppressed >90% in PRP at 3 hours
      after dose at the MTD and in tumor at pictilisib doses associated with AUC >20
      h.MUmol/L. Significant increase in plasma insulin and glucose levels, and >25%
      decrease in (18)F-FDG uptake by PET in 7 of 32 evaluable patients confirmed
      target modulation. A patient with V600E BRAF-mutant melanoma and another with
      platinum-refractory epithelial ovarian cancer exhibiting PTEN loss and PIK3CA
      amplification demonstrated partial response by RECIST and GCIG-CA125 criteria,
      respectively. CONCLUSION: Pictilisib was safely administered with a dose
      proportional pharmacokinetic profile, on-target pharmacodynamic activity at dose
      levels >=100 mg and signs of antitumor activity. The recommended phase II dose
      was continuous dosing at 330 mg once-daily.

PMID- 25370473
TI  - Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic
      melanoma patients.
AB  - BACKGROUND: MEK1 mutations in melanoma can confer resistance to BRAF inhibitors,
      although preexisting MEK1(P124) mutations do not preclude clinical responses. We
      sought to determine whether recurrent, preexisting MEK1(P124) mutations affected
      clinical outcome in BRAF inhibitor-treated patients with melanoma. METHODS: Data
      from four published datasets were analyzed to determine whether preexisting
      MEK1(P124) mutations affect radiologic response or progression-free survival
      (PFS) in patients with BRAF(V600)-mutant metastatic melanoma treated with
      vemurafenib or dabrafenib. The effects of MEK1(P124) mutations on MAPK pathway
      activity and response to BRAF inhibition were also investigated in a series of
      cell models. RESULTS: In a pooled analysis of 123 patients, the presence of a
      pretreatment MEK1(P124) mutation (N = 12, 10%) was associated with a poorer
      RECIST response (33% vs. 72% in MEK1(P124Q/S) vs. MEK1(P124) wild-type, P =
      0.018), and a shorter PFS (median 3.1 vs. 4.8 months, P = 0.004). Furthermore,
      MEK1(P124Q/S) mutations were shown to have independent kinase activity and
      introduction of these mutations into a BRAF-mutant melanoma cell line diminished
      inhibition of ERK phosphorylation by dabrafenib and enhanced clonogenic survival
      in the presence of dabrafenib compared with cells ectopically expressing wild
      type MEK1. Consistent with these data, two BRAF-mutant cell lines with endogenous
      MEK1(P124) mutations showed intermediate sensitivity to dabrafenib, but were
      highly sensitive to downstream inhibition of MEK or ERK. CONCLUSION: Taken
      together, our data indicate that preexisting MEK1(P124) mutations are associated
      with a reduced response to BRAF inhibitor therapy and identify a subset of
      patients with BRAF-mutant melanoma likely to benefit from combination therapies
      involving MEK or ERK inhibitors.

PMID- 25370474
TI  - Perioperative respiratory complications following awake and deep extubation in
      children undergoing adenotonsillectomy.
AB  - BACKGROUND: Perioperative respiratory complications after adenotonsillectomy
      (T&A) are common and have been described to occur more frequently in children
      below 3 years of age, those with cranio-facial abnormalities, Down syndrome,
      obstructive sleep apnea, morbid obesity, and failure to thrive. AIMS: To
      investigate the association between awake vs deep tracheal extubation and
      perioperative respiratory conditions. RESULTS: The primary outcome was any
      perioperative respiratory complication. Major complications included the need for
      airway reinstrumentation, continuous or bi-level positive airway pressure (CPAP
      or BiPAP) and ventilation, or pharmacologic intervention for managing airway
      obstruction. Minor respiratory complications included persistent hypoxemia
      defined as oxygen saturation (SpO2 ) <92% for >=30 s or postoperative oxygen
      dependence for hypoxemia for >=15 min. There was no statistically significant
      difference in the incidence of any perioperative respiratory complication in
      children undergoing an awake vs deep extubation (18.5% and 18.9% for awake and
      deep extubation, respectively (P = 0.93)). Only low weight (<=14 kg) was
      associated with increased perioperative respiratory complications (P = 0.005). In
      this study, factors found not to be statistically significant with perioperative
      respiratory complications included age; presence of Down syndrome, cranio-facial
      abnormality, or cerebral palsy; obstructive sleep apnea confirmed by
      polysomnography; diagnosis of obstructive sleep apnea by clinical history;
      presence of an upper respiratory tract infection (URI) within 2 weeks of
      presentation; history of reactive airway disease; status at extubation; endtidal
      sevoflurane and carbon dioxide concentrations at extubation; total intraoperative
      opioids administered in morphine equivalents (mg.kg(-1) ); administration of
      propofol at extubation; and intraoperative administration of an anticholinergic
      drug. CONCLUSIONS: There was no difference in the incidence of perioperative
      respiratory complications in children undergoing a T&A following an awake vs deep
      extubation. Only weight <=14 kg was associated with increased perioperative
      respiratory complications.

PMID- 25370475
TI  - Novel in silico technology in combination with microarrays: a state-of-the-art
      technology for allergy diagnosis and management?
AB  - 'Allergen microarrays, in poly-sensitized allergic patients, represent a real
      value added in the accurate IgE profiling and in the identification of
      allergen(s) to administer for an effective allergen immunotherapy.' Allergen
      microarrays (AMA) were developed in the early 2000s to improve the diagnostic
      pathway of patients with allergic reactions. Nowadays, AMA are constituted by
      more than 100 different components (either purified or recombinant), representing
      genuine and cross-reacting molecules from plants and animals. The cost of the
      procedure had suggested its use as third-level diagnostics (following in vivo-
      and in vitro-specific IgE tests) in poly-sensitized patients. The complexity of
      the interpretation had inspired the development of in silico technologies to help
      clinicians in their work. Both machine learning techniques and expert systems are
      now available. In particular, an expert system that has been recently developed
      not only identifies positive and negative components but also lists dangerous
      components and classifies patients based on their potential responsiveness to
      allergen immunotherapy, on the basis of published algorithms. For these
      characteristics, AMA represents the state-of-the-art technology for allergy
      diagnosis in poly-sensitized patients. 

PMID- 25370476
TI  - Optimal use of left ventriculography at the time of cardiac catheterization: a
      consensus statement from the Society for Cardiovascular Angiography and
      Interventions.
AB  - The rationale to perform left ventriculography at the time of cardiac
      catheterization has been little studied. The technique and frequency of use of
      left ventriculography vary by geographic regions, institutions, and individuals.
      Despite the recent publication of guidelines and appropriate use criteria for
      coronary angiography, revascularization, and noninvasive imaging, to date there
      have been no specific guidelines on the performance of left ventriculography.
      When left ventriculography is performed, proper technique must be used to
      generate high quality data which can direct patient management. The decision to
      perform left ventriculography in place of, or in addition to, other forms of
      ventricular assessment should be made taking into account the clinical context
      and the type of information each study provides. This paper attempts to show the
      role of left ventriculography at the time of coronary angiography or left heart
      catheterization. The recommendations in this document are not formal guidelines
      but are based on the consensus of this writing group. These recommendations
      should be tested through clinical research studies. Until such studies are
      performed, the writing group believes that adoption of these recommendations will
      lead to a more standardized application of ventriculography and improve the
      quality of care provided to cardiac patients. (c) 2014 Wiley Periodicals, Inc. 

PMID- 25370477
TI  - Potential of 80-kV high-resolution cone-beam CT imaging combined with an
      optimized protocol for neurological surgery.
AB  - INTRODUCTION: With the development of computed tomography (CT) and magnetic
      resonance imaging (MRI), the use of conventional X-ray angiography including
      digital subtraction angiography (DSA) for diagnosis has decreased, as it is an
      invasive technique with a risk of neurological complications. However, X-ray
      angiography imaging technologies have progressed markedly, along with the
      development of endovascular treatments. A newly developed angiography technique
      using cone-beam CT (CBCT) technology provides higher spatial resolution than
      conventional CT. Herein, we describe the potential of this technology for
      neurosurgical operations with reference to clinical cases. METHODS: Two hundred
      twenty-five patients who received 80-kV high-resolution CBCT from July 2011 to
      June 2014 for preoperative examinations were included in this study. For
      pathognomonical cases, images were taken with suitable reconstruction modes and
      contrast protocols. Cases were compared with intraoperative findings or images
      from other modalities. RESULTS: We observed the following pathognomonical types:
      (1) imaging of the distal dural ring (DDR) and the surrounding structure for
      paraclinoid aneurysms, (2) imaging of thin blood vessels, and (3) imaging of both
      brain tumors and their surrounding anatomy. Our devised 80-kV high-resolution
      CBCT imaging system provided clear visualization of detailed anatomy when
      compared with other modalities in almost all cases. Only two cases provided poor
      visualization due to movement artifact. CONCLUSION: Eighty-kilovolt high
      resolution CBCT has the potential to provide detailed anatomy for neurosurgical
      operations when utilizing suitable modes and contrast protocols.

PMID- 25370478
TI  - Use of herbal medicine during pregnancy among women with access to public
      healthcare in Nairobi, Kenya: a cross-sectional survey.
AB  - BACKGROUND: Maternal health is a public health priority in many African
      countries, but little is known about herbal medicine use in pregnancy. This study
      aimed to determine the pattern of use of herbal medicine in an urban setting,
      where women have relatively high access to public healthcare. METHODS: This cross
      sectional study included 333 women attending a childcare clinic in a district
      public health hospital in Nairobi, Kenya, during January and February, 2012, and
      who had delivered a baby within the past 9 months. Qualitative and quantitative
      data on herbal medicine use during their latest pregnancy were collected through
      an interviewer-administered questionnaire. Data was analysed descriptively and
      the Chi square test and Fishers' exact test used to analyse relationships among
      variables. RESULTS: About 12% of women used herbal medicine during their most
      recent pregnancy. The use of herbal medicine was associated with a lower level of
      education (p = 0.007) and use before the index pregnancy (p <0.001). Only 12.5%
      of users disclosed such use to healthcare professionals, and about 20% used
      herbal medicine concomitantly with Western medicine for the same
      illness/condition. Women used herbal medicine for back pain, toothache,
      indigestion and infectious diseases, such as respiratory tract infections and
      malaria. A proportion of users took herbal medicine only to boost or maintain
      health. There were high rates of self-prescribing, as well as sourcing from
      family and friends. Beliefs about safety and efficacy were consistent with
      patterns of use or non-use, although both users and non-users were unsure about
      the safety and contraindications of Western medicine during pregnancy compared
      with that of herbal medicine. CONCLUSION: Herbal medicine is used by 12% of
      pregnant women with access to healthcare in an urban context in Kenya, and often
      occurs without the knowledge of healthcare practitioners. Healthcare
      professionals should play a role in rational use of both herbal and Western
      medicine, by discussing contraindications and the potential for drug-herb
      interactions with patients. More studies are needed into the use of herbal
      medicines during pregnancy, labour and the postpartum period in different
      geographical areas, and into the health outcomes associated with their use.

PMID- 25370480
TI  - Strengthening primary health care-but how?

PMID- 25370481
TI  - Morphine protects SH-SY5Y human neuroblastoma cells against Dickkopf1-induced
      apoptosis.
AB  - Morphine is used to relieve pain in patients with cancer in terminal phases.
      Dickkopf-1 (DKK1), a secreted protein, is a negative regulator of the Wnt/beta
      catenin signaling pathway. Morphine and DKK1 are associated with tumorigenesis.
      However, to the best of our knowledge, there is no study evaluating the effects
      of these two factors simultaneously. In the present study, the effects of
      morphine and DKK1 on neuroblastoma cells in vivo and in vitro were evaluated. To
      establish the in vitro effects of DKK1 and morphine, human neuroblastoma SH-SY5Y
      cells were transfected with a DKK1-expressing plasmid and cell migration,
      apoptosis, migration and invasion were evaluated prior to and following morphine
      treatment. The results indicated that DKK1 induced apoptosis and inhibited the
      mobility of neuroblastoma cells and that morphine attenuated these DKK1-induced
      effects. To evaluate the effects of DKK1 and morphine in vivo, a mouse model of
      neuroblastoma was established, where mice bearing tumors of native SH-SY5Y cells
      were injected with DKK1. Tumor size, spatial memory and survival rate were
      investigated in untreated, DKK1-treated and DKK1+morphine-treated mice. Water
      maze and T-maze tests were performed, which revealed that DKK1-treated mice
      exhibited a better memory than DKK1 + morphine-treated mice. The expression of
      DKK1 in established xenografted tumors was associated with decreased tumor size
      and an increased survival rate, whereas morphine reversed these effects.
      Furthermore, it was confirmed that morphine and DKK1 take effect, at least in
      part, via the Wnt/beta-catenin signaling pathway. The results of the present
      study indicate that morphine may protect neuroblastoma cells and thus, it may be
      used in neuroblastoma patients. 

PMID- 25370482
TI  - Re-expression of Lactotransferrin, a candidate tumor suppressor inactivated by
      promoter hypermethylation, impairs the malignance of oral squamous cell carcinoma
      cells.
AB  - BACKGROUND: Lactotransferrin (LTF) has been confirmed to act as a tumor
      suppressor in multiple cancers; however, its roles in oral squamous cell
      carcinoma (OSCC), one of malignant head and neck carcinomas, has not been
      explored. METHODS: Here, the expression of LTF in OSCC tissues and TCA8113 cells
      was detected with RT-PCR, qPCR, and IHC. And the correlation between LTF
      expression and OSCC metastasis was assessed. MS-PCR was performed to reveal the
      methylation status in promoter regions of LTF both in OSCC tissue samples and
      cells. The influences of 5-Aza-Cdc treatment to the methylation status and
      expression levels of LTF were also analyzed. At last, the functions of LTF in
      OSCC progression were demonstrated by MTT analysis, clone formation assay, and
      cell cycle analysis in TCA8113 cells with forced ectopic expression of LTF.
      RESULTS: LTF showed a low or null expression pattern in OSCC tissues and cells,
      at least partially, due to the hypermethylated status in promoter regions for 5
      Aza-Cdc, a methyltransferase inhibitor, could restore the expression of LTF in
      TCA8113 cells. And the expression level of LTF exhibited a negative correlation
      with OSCC metastasis. CONCLUSIONS: Re-expression of LTF inhibited the growth,
      proliferation, as well as cell cycle progression of TCA8113 cells. In conclusion,
      hypermethylation contributes much to LTF inactivation in OSCC. And LTF can
      partially reverse the malignant phenotypes of OSCC cells and may be served as a
      potential target for diagnosis and therapy of OSCC in future.

PMID- 25370483
TI  - Versatile control of Plasmodium falciparum gene expression with an inducible
      protein-RNA interaction.
AB  - The available tools for conditional gene expression in Plasmodium falciparum are
      limited. Here, to enable reliable control of target gene expression, we build a
      system to efficiently modulate translation. We overcame several problems
      associated with other approaches for regulating gene expression in P. falciparum.
      Specifically, our system functions predictably across several native and
      engineered promoter contexts, and affords control over reporter and native
      parasite proteins irrespective of their subcellular compartmentalization.
      Induction and repression of gene expression are rapid, homogeneous and stable
      over prolonged periods. To demonstrate practical application of our system, we
      used it to reveal direct links between antimalarial drugs and their native
      parasite molecular target. This is an important outcome given the rapid spread of
      resistance, and intensified efforts to efficiently discover and optimize new
      antimalarial drugs. Overall, the studies presented highlight the utility of our
      system for broadly controlling gene expression and performing functional genetics
      in P. falciparum. 

PMID- 25370485
TI  - Altered Network Oscillations and Functional Connectivity Dynamics in Children
      Born Very Preterm.
AB  - Structural brain connections develop atypically in very preterm children, and
      altered functional connectivity is also evident in fMRI studies. Such alterations
      in brain network connectivity are associated with cognitive difficulties in this
      population. Little is known, however, about electrophysiological interactions
      among specific brain networks in children born very preterm. In the present
      study, we recorded magnetoencephalography while very preterm children and full
      term controls performed a visual short-term memory task. Regions expressing task
      dependent activity changes were identified using beamformer analysis, and inter
      regional phase synchrony was calculated. Very preterm children expressed altered
      regional recruitment in distributed networks of brain areas, across standard
      physiological frequency ranges including the theta, alpha, beta and gamma bands.
      Reduced oscillatory synchrony was observed among task-activated brain regions in
      very preterm children, particularly for connections involving areas critical for
      executive abilities, including middle frontal gyrus. These findings suggest that
      inability to recruit neurophysiological activity and interactions in distributed
      networks including frontal regions may contribute to difficulties in cognitive
      development in children born very preterm. 

PMID- 25370484
TI  - Automated Hippocampal Subfield Measures as Predictors of Conversion from Mild
      Cognitive Impairment to Alzheimer's Disease in Two Independent Cohorts.
AB  - Previous studies have shown that hippocampal subfields may be differentially
      affected by Alzheimer's disease (AD). This study used an automated analysis
      technique and two large cohorts to (1) investigate patterns of subfield volume
      loss in mild cognitive impairment (MCI) and AD, (2) determine the pattern of
      subfield volume loss due to age, gender, education, APOE epsilon4 genotype, and
      neuropsychological test scores, (3) compare combined subfield volumes to
      hippocampal volume alone at discriminating between AD and healthy controls (HC),
      and predicting future MCI conversion to AD at 12 months. 1,069 subjects were
      selected from the AddNeuroMed and Alzheimer's disease neuroimaging initiative
      (ADNI) cohorts. Freesurfer was used for automated segmentation of the hippocampus
      and hippocampal subfields. Orthogonal partial least squares to latent structures
      (OPLS) was used to train models on AD and HC subjects using one cohort for
      training and the other for testing and the combined cohort was used to predict
      MCI conversion. MANCOVA and linear regression analyses showed multiple subfield
      volumes including Cornu Ammonis 1 (CA1), subiculum and presubiculum were
      atrophied in AD and MCI and were related to age, gender, education, APOE epsilon4
      genotype, and neuropsychological test scores. For classifying AD from HC,
      combined subfield volumes achieved comparable classification accuracy (81.7%) to
      total hippocampal (80.7%), subiculum (81.2%) and presubiculum (80.6%) volume. For
      predicting MCI conversion to AD combined subfield volumes and presubiculum volume
      were more accurate (81.1%) than total hippocampal volume. (76.7%).

PMID- 25370486
TI  - The phenotypic spectrum of progressive supranuclear palsy: a retrospective
      multicenter study of 100 definite cases.
AB  - The phenotypic variability of progressive supranuclear palsy (PSP) may account
      for its frequent misdiagnosis, in particular in early stages of the disease.
      However, large multicenter studies to define the frequency and natural history of
      PSP phenotypes are missing. In a cohort of 100 autopsy-confirmed patients we
      studied the phenotypic spectrum of PSP by retrospective chart review. Patients
      were derived from five brain banks with expertise in neurodegenerative disorders
      with referrals from multiple academic hospitals. The clinical characteristics of
      the 100 cases showed remarkable heterogeneity. Most strikingly, only 24% of cases
      presented as Richardson's Syndrome (RS), and more than half of the cases either
      showed overlapping features of several predescribed phenotypes, or features not
      fitting proposed classification criteria for PSP phenotypes. Classification of
      patients according to predominant clinical features in the first 2 years of the
      disease course allowed a more comprehensive description of the phenotypic
      spectrum. These predominance types differed significantly with regard to survival
      time and frequency of cognitive deficits. In summary, the phenotypic spectrum of
      PSP may be broader and more variable than previously described in single-center
      studies. Thus, too strict clinical criteria defining distinct phenotypes may not
      reflect this variability. A more pragmatic clinical approach using predominance
      types could potentially be more helpful in the early recognition of and for
      making prognostic predictions for these patients. Given the limitations arising
      from the retrospective nature of this analysis, a systematic validation in a
      prospective cohort study is imperative.

PMID- 25370487
TI  - Localization of SUCLA2 and SUCLG2 subunits of succinyl CoA ligase within the
      cerebral cortex suggests the absence of matrix substrate-level phosphorylation in
      glial cells of the human brain.
AB  - We have recently shown that the ATP-forming SUCLA2 subunit of succinyl-CoA
      ligase, an enzyme of the citric acid cycle, is exclusively expressed in neurons
      of the human cerebral cortex; GFAP- and S100-positive astroglial cells did not
      exhibit immunohistoreactivity or in situ hybridization reactivity for either
      SUCLA2 or the GTP-forming SUCLG2. However, Western blotting of post mortem
      samples revealed a minor SUCLG2 immunoreactivity. In the present work we sought
      to identify the cell type(s) harboring SUCLG2 in paraformaldehyde-fixed, free
      floating surgical human cortical tissue samples. Specificity of SUCLG2 antiserum
      was supported by co-localization with mitotracker orange staining of
      paraformaldehyde-fixed human fibroblast cultures, delineating the mitochondrial
      network. In human cortical tissue samples, microglia and oligodendroglia were
      identified by antibodies directed against Iba1 and myelin basic protein,
      respectively. Double immunofluorescence for SUCLG2 and Iba1 or myelin basic
      protein exhibited no co-staining; instead, SUCLG2 appeared to outline the
      cerebral microvasculature. In accordance to our previous work there was no co
      localization of SUCLA2 immunoreactivity with either Iba1 or myelin basic protein.
      We conclude that SUCLG2 exist only in cells forming the vasculature or its
      contents in the human brain. The absence of SUCLA2 and SUCLG2 in human glia is in
      compliance with the presence of alternative pathways occurring in these cells,
      namely the GABA shunt and ketone body metabolism which do not require succinyl
      CoA ligase activity, and glutamate dehydrogenase 1, an enzyme exhibiting
      exquisite sensitivity to inhibition by GTP. 

PMID- 25370488
TI  - Genomic epidemiology of the Haitian cholera outbreak: a single introduction
      followed by rapid, extensive, and continued spread characterized the onset of the
      epidemic.
AB  - For centuries, cholera has been one of the most feared diseases. The causative
      agent Vibrio cholerae is a waterborne Gram-negative enteric pathogen eliciting a
      severe watery diarrheal disease. In October 2010, the seventh pandemic reached
      Haiti, a country that had not experienced cholera for more than a century. By
      using whole-genome sequence typing and mapping strategies of 116 serotype O1
      strains from global sources, including 44 Haitian genomes, we present a detailed
      reconstructed evolutionary history of the seventh pandemic with a focus on the
      Haitian outbreak. We catalogued subtle genomic alterations at the nucleotide
      level in the genome core and architectural rearrangements from whole-genome map
      comparisons. Isolates closely related to the Haitian isolates caused several
      recent outbreaks in southern Asia. This study provides evidence for a single
      source introduction of cholera from Nepal into Haiti followed by rapid,
      extensive, and continued clonal expansion. The phylogeographic patterns in both
      southern Asia and Haiti argue for the rapid dissemination of V. cholerae across
      the landscape necessitating real-time surveillance efforts to complement the
      whole-genome epidemiological analysis. As eradication efforts move forward,
      phylogeographic knowledge will be important for identifying persistent sources
      and monitoring success at regional levels. The results of molecular and
      epidemiological analyses of this outbreak suggest that an indigenous Haitian
      source of V. cholerae is unlikely and that an indigenous source has not
      contributed to the genomic evolution of this clade. IMPORTANCE: In this genomic
      epidemiology study, we have applied high-resolution whole-genome-based sequence
      typing methodologies on a comprehensive set of genome sequences that have become
      available in the aftermath of the Haitian cholera epidemic. These sequence
      resources enabled us to reassess the degree of genomic heterogeneity within the
      Vibrio cholerae O1 serotype and to refine boundaries and evolutionary
      relationships. The established phylogenomic framework showed how outbreak
      isolates fit into the global phylogeographic patterns compared to a comprehensive
      globally and temporally diverse strain collection and provides strong molecular
      evidence that points to a nonindigenous source of the 2010 Haitian cholera
      outbreak and refines epidemiological standards used in outbreak investigations
      for outbreak inclusion/exclusion following the concept of genomic epidemiology.
      The generated phylogenomic data have major public health relevance in translating
      sequence-based information to assist in future diagnostic, epidemiological,
      surveillance, and forensic studies of cholera.

PMID- 25370489
TI  - Bone marrow dendritic cells from mice with an altered microbiota provide
      interleukin 17A-dependent protection against Entamoeba histolytica colitis.
AB  - There is an emerging paradigm that the human microbiome is central to many
      aspects of health and may have a role in preventing enteric infection. Entamoeba
      histolytica is a major cause of amebic diarrhea in developing countries. It
      colonizes the colon lumen in close proximity to the gut microbiota.
      Interestingly, not all individuals are equally susceptible to E. histolytica
      infection. Therefore, as the microbiota is highly variable within individuals, we
      sought to determine if a component of the microbiota could regulate
      susceptibility to infection. In studies utilizing a murine model, we demonstrated
      that colonization of the gut with the commensal Clostridia-related bacteria known
      as segmented filamentous bacteria (SFB) is protective during E. histolytica
      infection. SFB colonization in this model was associated with elevated cecal
      levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow
      derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL
      23 production in response to stimulation with trophozoites. Adoptive transfer of
      BMDCs from an SFB(+) to an SFB(-) mouse was sufficient to provide protection
      against E. histolytica. IL-17A induction during BMDC transfer was necessary for
      this protection. This work demonstrates that intestinal colonization with a
      specific commensal bacterium can provide protection during amebiasis in a murine
      model. Most importantly, this work demonstrates that the microbiome can mediate
      protection against an enteric infection via extraintestinal effects on bone
      marrow-derived dendritic cells. IMPORTANCE: Entamoeba histolytica is the
      causative agent of amebiasis, an infectious disease that contributes
      significantly to morbidity and mortality due to diarrhea in the developing world.
      We showed in a murine model that colonization with the commensal members of the
      Clostridia known as SFB provides protection against E. histolytica and that
      dendritic cells from SFB-colonized mice alone can recapitulate protection.
      Understanding interactions between enteropathogens, commensal intestinal
      bacteria, and the mucosal immune response, including dendritic cells, will help
      in the development of effective treatments for this disease and other infectious
      and inflammatory diseases. The demonstration of immune-mediated protection due to
      communication from the microbiome to the bone marrow represents an emerging field
      of study that will yield unique approaches to the development of these
      treatments.

PMID- 25370490
TI  - Comparative genomics of pneumocystis species suggests the absence of genes for
      myo-inositol synthesis and reliance on inositol transport and metabolism.
AB  - In the context of deciphering the metabolic strategies of the obligate pathogenic
      fungi in the genus Pneumocystis, the genomes of three species (P. carinii, P.
      murina, and P. jirovecii) were compared among themselves and with the free
      living, phylogenetically related fission yeast (Schizosaccharomyces pombe). The
      underrepresentation of amino acid metabolism pathways compared to those in S.
      pombe, as well as the incomplete steroid biosynthesis pathway, were confirmed for
      P. carinii and P. jirovecii and extended to P. murina. All three Pneumocystis
      species showed overrepresentation of the inositol phosphate metabolism pathway
      compared to that in the fission yeast. In addition to those known in S. pombe,
      four genes, encoding inositol-polyphosphate multikinase (EC 2.7.1.151), inositol
      pentakisphosphate 2-kinase (EC 2.7.1.158), phosphoinositide 5-phosphatase (EC
      3.1.3.36), and inositol-1,4-bisphosphate 1-phosphatase (EC 3.1.3.57), were
      identified in the two rodent Pneumocystis genomes, P. carinii and P. murina. The
      P. jirovecii genome appeared to contain three of these genes but lacked
      phosphoinositide 5-phosphatase. Notably, two genes encoding enzymes essential for
      myo-inositol synthesis, inositol-1-phosphate synthase (INO1) and inositol
      monophosphatase (INM1), were absent from all three genomes, suggesting that
      Pneumocystis species are inositol auxotrophs. In keeping with the need to acquire
      exogenous inositol, two genes with products homologous to fungal inositol
      transporters, ITR1 and ITR2, were identified in P. carinii and P. murina, while
      P. jirovecii contained only the ITR1 homolog. The ITR and inositol metabolism
      genes in P. murina and P. carinii were expressed during fulminant infection as
      determined by reverse transcriptase real-time PCR of cDNA from infected lung
      tissue. Supplementation of in vitro culture with inositol yielded significant
      improvement of the viability of P. carinii for days 7 through 14. IMPORTANCE:
      Microbes in the genus Pneumocystis are obligate pathogenic fungi that reside in
      mammalian lungs and cause Pneumocystis pneumonia in hosts with weakened immune
      systems. These fungal infections are not responsive to standard antifungal
      therapy. A long-term in vitro culture system is not available for these fungi,
      impeding the study of their biology and genetics and new drug development. Given
      that all genomes of the Pneumocystis species analyzed lack the genes for inositol
      synthesis and contain inositol transporters, Pneumocystis fungi, like S. pombe,
      appear to be inositol auxotrophs. Inositol is important for the pathogenesis,
      virulence, and mating processes in Candida albicans and Cryptococcus neoformans,
      suggesting similar importance within the Pneumocystis species as well. This is
      the first report to (i) characterize genes in the inositol phosphate metabolism
      and transport pathways in Pneumocystis species and (ii) identify inositol as a
      supplement that improved the viability of P. carinii in in vitro culture.

PMID- 25370491
TI  - Evolution of invasion in a diverse set of Fusobacterium species.
AB  - The diverse Fusobacterium genus contains species implicated in multiple clinical
      pathologies, including periodontal disease, preterm birth, and colorectal cancer.
      The lack of genetic tools for manipulating these organisms leaves us with little
      understanding of the genes responsible for adherence to and invasion of host
      cells. Actively invading Fusobacterium species can enter host cells
      independently, whereas passively invading species need additional factors, such
      as compromise of mucosal integrity or coinfection with other microbes. We applied
      whole-genome sequencing and comparative analysis to study the evolution of active
      and passive invasion strategies and to infer factors associated with active forms
      of host cell invasion. The evolution of active invasion appears to have followed
      an adaptive radiation in which two of the three fusobacterial lineages acquired
      new genes and underwent expansions of ancestral genes that enable active forms of
      host cell invasion. Compared to passive invaders, active invaders have much
      larger genomes, encode FadA-related adhesins, and possess twice as many genes
      encoding membrane-related proteins, including a large expansion of surface
      associated proteins containing the MORN2 domain of unknown function. We predict a
      role for proteins containing MORN2 domains in adhesion and active invasion. In
      the largest and most comprehensive comparison of sequenced Fusobacterium species
      to date, we have generated a testable model for the molecular pathogenesis of
      Fusobacterium infection and illuminate new therapeutic or diagnostic strategies.
      IMPORTANCE: Fusobacterium species have recently been implicated in a broad
      spectrum of human pathologies, including Crohn's disease, ulcerative colitis,
      preterm birth, and colorectal cancer. Largely due to the genetic intractability
      of member species, the mechanisms by which Fusobacterium causes these pathologies
      are not well understood, although adherence to and active invasion of host cells
      appear important. We examined whole-genome sequence data from a diverse set of
      Fusobacterium species to identify genetic determinants of active forms of host
      cell invasion. Our analyses revealed that actively invading Fusobacterium species
      have larger genomes than passively invading species and possess a specific
      complement of genes-including a class of genes of unknown function that we
      predict evolved to enable host cell adherence and invasion. This study provides
      an important framework for future studies on the role of Fusobacterium in
      pathologies such as colorectal cancer.

PMID- 25370492
TI  - Improving microbial biogasoline production in Escherichia coli using tolerance
      engineering.
AB  - Engineering microbial hosts for the production of fungible fuels requires
      mitigation of limitations posed on the production capacity. One such limitation
      arises from the inherent toxicity of solvent-like biofuel compounds to production
      strains, such as Escherichia coli. Here we show the importance of host
      engineering for the production of short-chain alcohols by studying the
      overexpression of genes upregulated in response to exogenous isopentenol. Using
      systems biology data, we selected 40 genes that were upregulated following
      isopentenol exposure and subsequently overexpressed them in E. coli.
      Overexpression of several of these candidates improved tolerance to exogenously
      added isopentenol. Genes conferring isopentenol tolerance phenotypes belonged to
      diverse functional groups, such as oxidative stress response (soxS, fpr, and
      nrdH), general stress response (metR, yqhD, and gidB), heat shock-related
      response (ibpA), and transport (mdlB). To determine if these genes could also
      improve isopentenol production, we coexpressed the tolerance-enhancing genes
      individually with an isopentenol production pathway. Our data show that
      expression of 6 of the 8 candidates improved the production of isopentenol in E.
      coli, with the methionine biosynthesis regulator MetR improving the titer for
      isopentenol production by 55%. Additionally, expression of MdlB, an ABC
      transporter, facilitated a 12% improvement in isopentenol production. To our
      knowledge, MdlB is the first example of a transporter that can be used to improve
      production of a short-chain alcohol and provides a valuable new avenue for host
      engineering in biogasoline production. IMPORTANCE: The use of microbial host
      platforms for the production of bulk commodities, such as chemicals and fuels, is
      now a focus of many biotechnology efforts. Many of these compounds are inherently
      toxic to the host microbe, which in turn places a limit on production despite
      efforts to optimize the bioconversion pathways. In order to achieve economically
      viable production levels, it is also necessary to engineer production strains
      with improved tolerance to these compounds. We demonstrate that microbial
      tolerance engineering using transcriptomics data can also identify targets that
      improve production. Our results include an exporter and a methionine biosynthesis
      regulator that improve isopentenol production, providing a starting point to
      further engineer the host for biogasoline production.

PMID- 25370493
TI  - Effect of copper treatment on the composition and function of the bacterial
      community in the sponge Haliclona cymaeformis.
AB  - Marine sponges are the most primitive metazoan and host symbiotic microorganisms.
      They are crucial components of the marine ecological system and play an essential
      role in pelagic processes. Copper pollution is currently a widespread problem and
      poses a threat to marine organisms. Here, we examined the effects of copper
      treatment on the composition of the sponge-associated bacterial community and the
      genetic features that facilitate the survival of enriched bacteria under copper
      stress. The 16S rRNA gene sequencing results showed that the sponge Haliclona
      cymaeformis harbored symbiotic sulfur-oxidizing Ectothiorhodospiraceae and
      photosynthetic Cyanobacteria as dominant species. However, these autotrophic
      bacteria decreased substantially after treatment with a high copper
      concentration, which enriched for a heterotrophic-bacterium-dominated community.
      Metagenomic comparison revealed a varied profile of functional genes and enriched
      functions, including bacterial motility and chemotaxis, extracellular
      polysaccharide and capsule synthesis, virulence-associated genes, and genes
      involved in cell signaling and regulation, suggesting short-period mechanisms of
      the enriched bacterial community for surviving copper stress in the
      microenvironment of the sponge. Microscopic observation and comparison revealed
      dynamic bacterial aggregation within the matrix and lysis of sponge cells. The
      bacteriophage community was also enriched, and the complete genome of a dominant
      phage was determined, implying that a lytic phage cycle was stimulated by the
      high copper concentration. This study demonstrated a copper-induced shift in the
      composition of functional genes of the sponge-associated bacterial community,
      revealing the selective effect of copper treatment on the functions of the
      bacterial community in the microenvironment of the sponge. IMPORTANCE: This study
      determined the bacterial community structure of the common sponge Haliclona
      cymaeformis and examined the effect of copper treatment on the community
      structure and functional gene composition, revealing that copper treatment had a
      selective effect on the functions of the bacterial community in the sponge. These
      findings suggest that copper pollution has an ecological impact on the sponge
      symbiont. The analysis showed that the untreated sponges hosted symbiotic
      autotrophic bacteria as dominant species, and the high-concentration copper
      treatment enriched for a heterotrophic bacterial community with enrichment for
      genes important for bacterial motility, supplementary cellular components,
      signaling and regulation, and virulence. Microscopic observation showed obvious
      bacterial aggregation and a reduction of sponge cell numbers in treated sponges,
      which suggested the formation of aggregates to reduce the copper concentration.
      The enrichment for functions of directional bacterial movement and supplementary
      cellular components and the formation of bacterial aggregates and phage
      enrichment are novel findings in sponge studies.

PMID- 25370494
TI  - Mass spectrometric analysis of L-cysteine metabolism: physiological role and fate
      of L-cysteine in the enteric protozoan parasite Entamoeba histolytica.
AB  - L-cysteine is essential for virtually all living organisms, from bacteria to
      higher eukaryotes. Besides having a role in the synthesis of virtually all
      proteins and of taurine, cysteamine, glutathione, and other redox-regulating
      proteins, L-cysteine has important functions under anaerobic/microaerophilic
      conditions. In anaerobic or microaerophilic protozoan parasites, such as
      Entamoeba histolytica, L-cysteine has been implicated in growth, attachment,
      survival, and protection from oxidative stress. However, a specific role of this
      amino acid or related metabolic intermediates is not well understood. In this
      study, using stable-isotope-labeled L-cysteine and capillary electrophoresis-time
      of flight mass spectrometry, we investigated the metabolism of L-cysteine in E.
      histolytica. [U-(13)C3, (15)N]L-cysteine was rapidly metabolized into three
      unknown metabolites, besides L-cystine and L-alanine. These metabolites were
      identified as thiazolidine-4-carboxylic acid (T4C), 2-methyl thiazolidine-4
      carboxylic acid (MT4C), and 2-ethyl-thiazolidine-4-carboxylic acid (ET4C), the
      condensation products of L-cysteine with aldehydes. We demonstrated that these 2
      (R)-thiazolidine-4-carboxylic acids serve for storage of L-cysteine. Liberation
      of L-cysteine occurred when T4C was incubated with amebic lysates, suggesting
      enzymatic degradation of these L-cysteine derivatives. Furthermore, T4C and MT4C
      significantly enhanced trophozoite growth and reduced intracellular reactive
      oxygen species (ROS) levels when it was added to cultures, suggesting that 2-(R)
      thiazolidine-4-carboxylic acids are involved in the defense against oxidative
      stress. IMPORTANCE: Amebiasis is a human parasitic disease caused by the
      protozoan parasite Entamoeba histolytica. In this parasite, L-cysteine is the
      principal low-molecular-weight thiol and is assumed to play a significant role in
      supplying the amino acid during trophozoite invasion, particularly when the
      parasites move from the anaerobic intestinal lumen to highly oxygenated tissues
      in the intestine and the liver. It is well known that E. histolytica needs a
      comparatively high concentration of L-cysteine for its axenic cultivation.
      However, the reason for and the metabolic fate of L-cysteine in this parasite are
      not well understood. Here, using a metabolomic and stable-isotope-labeled
      approach, we investigated the metabolic fate of this amino acid in these
      parasites. We found that L-cysteine inside the cell rapidly reacts with aldehydes
      to form 2-(R)-thiazolidine-4-carboxylic acid. We showed that these 2-(R)
      thiazolidine-4-carboxylic derivatives serve as an L-cysteine source, promote
      growth, and protect cells against oxidative stress by scavenging aldehydes and
      reducing the ROS level. Our findings represent the first demonstration of 2-(R)
      thiazolidine-4-carboxylic acids and their roles in protozoan parasites.

PMID- 25370495
TI  - Deep sequencing identifies noncanonical editing of Ebola and Marburg virus RNAs
      in infected cells.
AB  - Deep sequencing of RNAs produced by Zaire ebolavirus (EBOV) or the Angola strain
      of Marburgvirus (MARV-Ang) identified novel viral and cellular mechanisms that
      diversify the coding and noncoding sequences of viral mRNAs and genomic RNAs. We
      identified previously undescribed sites within the EBOV and MARV-Ang mRNAs where
      apparent cotranscriptional editing has resulted in the addition of non-template
      encoded residues within the EBOV glycoprotein (GP) mRNA, the MARV-Ang
      nucleoprotein (NP) mRNA, and the MARV-Ang polymerase (L) mRNA, such that novel
      viral translation products could be produced. Further, we found that the well
      characterized EBOV GP mRNA editing site is modified at a high frequency during
      viral genome RNA replication. Additionally, editing hot spots representing sites
      of apparent adenosine deaminase activity were found in the MARV-Ang NP 3'
      untranslated region. These studies identify novel filovirus-host interactions and
      reveal production of a greater diversity of filoviral gene products than was
      previously appreciated. IMPORTANCE: This study identifies novel mechanisms that
      alter the protein coding capacities of Ebola and Marburg virus mRNAs. Therefore,
      filovirus gene expression is more complex and diverse than previously recognized.
      These observations suggest new directions in understanding the regulation of
      filovirus gene expression.

PMID- 25370496
TI  - Comparative analyses of nonpathogenic, opportunistic, and totally pathogenic
      mycobacteria reveal genomic and biochemical variabilities and highlight the
      survival attributes of Mycobacterium tuberculosis.
AB  - Mycobacterial evolution involves various processes, such as genome reduction,
      gene cooption, and critical gene acquisition. Our comparative genome size
      analysis of 44 mycobacterial genomes revealed that the nonpathogenic (NP) genomes
      were bigger than those of opportunistic (OP) or totally pathogenic (TP)
      mycobacteria, with the TP genomes being smaller yet variable in size--their
      genomic plasticity reflected their ability to evolve and survive under various
      environmental conditions. From the 44 mycobacterial species, 13 species,
      representing TP, OP, and NP, were selected for genomic-relatedness analyses.
      Analysis of homologous protein-coding genes shared between Mycobacterium indicus
      pranii (NP), Mycobacterium intracellulare ATCC 13950 (OP), and Mycobacterium
      tuberculosis H37Rv (TP) revealed that 4,995 (i.e., ~95%) M. indicaus pranii
      proteins have homology with M. intracellulare, whereas the homologies among M.
      indicus pranii, M. intracellulare ATCC 13950, and M. tuberculosis H37Rv were
      significantly lower. A total of 4,153 (~79%) M. indicus pranii proteins and 4,093
      (~79%) M. intracellulare ATCC 13950 proteins exhibited homology with the M.
      tuberculosis H37Rv proteome, while 3,301 (~82%) and 3,295 (~82%) M. tuberculosis
      H37Rv proteins showed homology with M. indicus pranii and M. intracellulare ATCC
      13950 proteomes, respectively. Comparative metabolic pathway analyses of TP/OP/NP
      mycobacteria showed enzymatic plasticity between M. indicus pranii (NP) and M.
      intracellulare ATCC 13950 (OP), Mycobacterium avium 104 (OP), and M. tuberculosis
      H37Rv (TP). Mycobacterium tuberculosis seems to have acquired novel alternate
      pathways with possible roles in metabolism, host-pathogen interactions,
      virulence, and intracellular survival, and by implication some of these could be
      potential drug targets. IMPORTANCE: The complete sequence analysis of
      Mycobacterium indicus pranii, a novel species of Mycobacterium shown earlier to
      have strong immunomodulatory properties and currently in use for the treatment of
      leprosy, places it evolutionarily at the point of transition to pathogenicity.
      With the purpose of establishing the importance of M. indicus pranii in providing
      insight into the virulence mechanism of tuberculous and nontuberculous
      mycobacteria, we carried out comparative genomic and proteomic analyses of 44
      mycobacterial species representing nonpathogenic (NP), opportunistic (OP), and
      totally pathogenic (TP) mycobacteria. Our results clearly placed M. indicus
      pranii as an ancestor of the M. avium complex. Analyses of comparative metabolic
      pathways between M. indicus pranii (NP), M. tuberculosis (TP), and M.
      intracellulare (OP) pointed to the presence of novel alternative pathways in M.
      tuberculosis with implications for pathogenesis and survival in the human host
      and identification of new drug targets.

PMID- 25370498
TI  - Synthetic biology for engineering acetyl coenzyme A metabolism in yeast.
AB  - The yeast Saccharomyces cerevisiae is a widely used cell factory for the
      production of fuels, chemicals, and pharmaceuticals. The use of this cell factory
      for cost-efficient production of novel fuels and chemicals requires high yields
      and low by-product production. Many industrially interesting chemicals are
      biosynthesized from acetyl coenzyme A (acetyl-CoA), which serves as a central
      precursor metabolite in yeast. To ensure high yields in production of these
      chemicals, it is necessary to engineer the central carbon metabolism so that
      ethanol production is minimized (or eliminated) and acetyl-CoA can be formed from
      glucose in high yield. Here the perspective of generating yeast platform strains
      that have such properties is discussed in the context of a major breakthrough
      with expression of a functional pyruvate dehydrogenase complex in the cytosol. 

PMID- 25370499
TI  - Does hospital volume predict outcomes and complications after total shoulder
      arthroplasty in the US?
AB  - OBJECTIVE: To assess the association of hospital procedure volume for total
      shoulder arthroplasty (TSA) with patient outcomes and complications. METHODS: We
      used the US Nationwide Inpatient Sample from 1998-2011 to study the association
      of hospital annual TSA procedure volume with patient characteristics and TSA
      outcomes, including discharge disposition (home versus inpatient facility),
      length of index hospitalization, postarthroplasty periprosthetic fracture, and
      revision. Annual hospital TSA volume was categorized as <5, 5-9, 10-14, 15-24,
      and >=25 TSA procedures annually. RESULTS: Patients receiving TSA at higher
      volume hospitals were more likely to be female (P < 0.0001) and white (P <
      0.0001). Compared to low volume hospitals (<5, 5-9, or 10-14 procedures
      annually), patients receiving TSA at higher volume hospitals (15-24 or >=25
      procedures annually) had significantly lower likelihood of being discharged to an
      inpatient medical facility: 16.5%, 13.4%, 13.0%, 12.7%, and 11.5%, respectively
      (P < 0.0001); hospital stay above the overall median: 46.6%, 40.4%, 36.6%, 34.4%,
      and 29.2%, respectively (P < 0.0001); postarthroplasty fracture: 1.2%, 0.8%,
      0.9%, 0.6%, and 0.8%, respectively (P = 0.0004); blood transfusion: 8%, 7.1%,
      6.7%, 7.1%, and 5.5%, respectively (P = 0.006); and TSA revision: 0.5%, 0.3%,
      0.2%, 0.3%, 0.3%, respectively (P = 0.045). CONCLUSION: In this study, we found
      that higher annual hospital TSA volume was associated with better TSA outcomes in
      the US. These findings document the impact of annual hospital TSA volume on TSA
      outcomes. Patients, surgeons, and policy-makers should be aware of these findings
      and take them into account in decision-making, policy decisions, and resource
      allocation.

PMID- 25370500
TI  - Adsorption and desorption behavior of asphaltene on polymer-brush-immobilized
      surfaces.
AB  - The adsorption behavior of a model compound for surface-active component of
      asphaltenes, N-(1-hexylheptyl)-N'-(12-carboxylicdodecyl) perylene-3,4,9,10
      tetracarboxylic bisimide (C5Pe), and detachment behavior of asphaltene deposit
      films for high-density polymer brushes were investigated. Zwitterionic poly(3-(N
      2-methacryloyloxyethyl-N,N-dimethyl)ammonatopropanesulfonate (PMAPS) brushes and
      hydrophobic poly(n-hexyl methacrylate) (PHMA) brushes exhibit less C5Pe
      adsorption than poly(methyl methacrylate) (PMMA). The asphaltene deposit films on
      the PHMA brush detached in a model oil (toluene/n-heptane=1/4 (v/v)), and the
      asphaltene films on the PMAPS brush detached in water. The antifouling character
      was explained by the interface free energy for the polymer-brush/asphaltenes
      (gammaSA) and polymer-brush/toluene (gammaSO).

PMID- 25370501
TI  - [Risk estimation of blood-borne infections by emergency room personnel].
AB  - BACKGROUND: Emergency department personnel are at risk of occupational exposure
      to blood-borne pathogens. Previous studies have shown that the prevalence of
      human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) virus
      infections among trauma patients is higher compared to the general population.
      OBJECTIVES: The aim of the study was to investigate the compliance rates of
      trauma team members in applying standard precautions, knowledge about the
      transmission risk of blood-borne infections and perceived risk of acquiring HIV,
      HBV and HCV. METHODS: An anonymous questionnaire was distributed to 100 trauma
      team members including physicians, nurses and medical students from different
      medical departments (e.g. surgery, radiology, anesthesia and internal medicine).
      RESULTS: The results of the questionnaire showed that trauma team members had
      insufficient knowledge of the risk of blood-borne pathogens, overestimated the
      risk of HCV infection and underused standard precautions during treatment of
      emergency trauma patients. CONCLUSION: Further educational measures for emergency
      department personnel are required to increase the knowledge of occupational
      infections and compliance with standard precautions. Every healthcare worker
      needs to be sufficiently vaccinated against HBV. In the case of injury awareness
      of all measures of post-exposure prophylaxis is of utmost importance for affected
      personnel.

PMID- 25370502
TI  - Enhanced downregulation of transforming growth factor-beta2 in rat retinal
      pigment epithelium cells by adeno-associated virus-mediated ribonucleic acid
      interference combined with ultrasound or microbubbles.
AB  - The present study was designed to determine the efficiency and safety of
      ultrasound (US) and/or US contrast agent microbubbles (MBs) in the delivery of
      type 2 recombinant adeno-associated virus-delivered transforming growth factor
      beta2 short hairpin ribonucleic acid encoding the enhanced green fluorescent
      protein gene (rAAV2-TGFbeta2 shRNA-EGFP) and the downregulation of TGFbeta2 in
      rat retinal pigment epithelium (RPE-J) cells. The effects of US and/or MBs on the
      delivery of rAAV2-EGFP and rAAV2-TGFbeta2 shRNA-EGFP were evaluated by
      fluorescence microscopy and flow cytometry. The potential toxicity of cell
      viability under various US or MB conditions was assessed by CellTiter 96(r)
      AQueous One solution cell proliferation assay. The level of TGFbeta2 mRNA in RPE
      J cells under various conditions was estimated by reverse transcription
      quantitative polymerase chain reaction analysis. The results obtained
      demonstrated that low-intensity US (0.5 W/cm2 and 30 sec) or SonoVue (MB:cell
      ratio, 40:1) increased the delivery efficiency of rAAV2-EGFP and rAAV2-TGFbeta2
      shRNA-EGFP to RPE-J cells, whereas the combination of US with MBs did not further
      increase but instead decreased rAAV transfection. Under the optimal conditions of
      rAAV delivery, enhanced TGFbeta2 gene silencing with a combination of US or
      SonoVue with rAAV2-TGFbeta2 shRNA resulted in a significant decrease in mRNA
      levels compared with rAAV2-TGFbeta2 shRNA alone. US or SonoVue was used safely to
      enhance the delivery of rAAV2-TGFbeta2 shRNA to RPE-J cells. A combination of the
      biological (rAAV2-TGFbeta2 shRNA) and physical (US or SonoVue) approaches
      downregulated the mRNA level of TGFbeta2 more effectively.

PMID- 25370503
TI  - Time trend of prevalence of self-reported cataract and its association with
      prolonged sitting in Taiwan from 2001 and 2013.
AB  - BACKGROUND: Prolong sitting has been found associated with metabolic disorders.
      Little is known about the self-reported cataract status in general population of
      Taiwan, not to mention its relation to prolong sitting. We aimed to examine the
      prevalence of cataract between 2001 and 2013 in Taiwan and to the association
      between prolonged sitting and cataract. METHODS: We used three data sets with
      those aged 40 years and older from the National Health Interview Survey (NHIS)
      from 2001 (n = 8334), 2009 (n = 11207), and 2013 (n = 10940). Subsequent
      statistical analyses involved chi-square test, t test, and logistic regression
      modeling. SUDAAN was used to account for sampling scheme. RESULTS: The prevalence
      of cataract ranged from 10.7% in 2001, 13.13% in 2009, to 11.84% in 2013.
      Participants who sat for more than 7 hours per day had a significantly higher
      risk of cataract (OR = 1.20, CI = (1.04-1.39)) compared with those who sat for
      fewer than 3 hours per day after controlling for age and other risk factors like
      being older or female, lower education level, not being currently employed,
      living in a highly urbanized area, having hypertension, diabetes, myopia, and
      being an former smoker (compared to a never smoker). CONCLUSION: Increased daily
      sitting time was associated with cataract, especially for people who sat more
      than 7 hours per day.

PMID- 25370504
TI  - Efficacy of a hybrid online training for panic symptoms and agoraphobia: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Recently, internet-based interventions have been proposed as
      effective treatments for people with panic disorder (PD). However, little is
      known about the clinical effects of integrating mobile technology into these
      interventions. Because users carry their smartphones with them throughout the
      day, we hypothesize that this technology can be used to significantly support
      individuals with monitoring and overcoming their PD symptoms. The aim of the
      present study is to evaluate the efficacy and cost-effectiveness of a newly
      developed hybrid intervention that combines internet/PC with smartphone delivery
      to treat the symptoms of PD. The intervention is based on cognitive behavioral
      therapy and consists of six modules over a total of six weeks. METHODS/DESIGN: A
      two-arm randomized controlled trial (RCT) will be conducted to evaluate the
      effects of a hybrid online training module for PD. Based on a power calculation
      (d =0.60; 1-beta of 80%; alpha =0.05), 90 participants with mild to moderate
      panic symptoms with or without agoraphobia (as assessed by the Panic and
      Agoraphobia Scale) will be recruited from the general population and randomly
      assigned to either the intervention group or a six-month waitlist control group.
      The primary outcome measure will be the severity of panic symptoms. Secondary
      outcomes will include depression, quality of life, and an observer-based rating
      of panic severity. Furthermore, data regarding acceptance and the usability of
      the smartphone app will be assessed. Assessments will take place at baseline as
      well as eight weeks, three months, and six months after randomization. Moreover,
      a cost-effectiveness analysis will be performed from a societal perspective. Data
      will be analyzed on an intention-to-treat basis and per protocol. DISCUSSION: To
      our knowledge, this RCT is one of the first to examine the efficacy of a hybrid
      online training for adult PD. This study seeks to contribute to the emerging
      field of hybrid online training. If the intervention is efficacious, then
      research on this hybrid online training should be extended. The cost
      effectiveness analysis will also indicate whether online training is an
      economical tool for treating PD among adults. TRIAL REGISTRATION: German Clinical
      Trial Register: DRKS00005223 (registered on 15 August 2013).

PMID- 25370506
TI  - Reply: To PMID 24782338.

PMID- 25370505
TI  - Study protocol: differential effects of diet and physical activity based
      interventions in pregnancy on maternal and fetal outcomes--individual patient
      data (IPD) meta-analysis and health economic evaluation.
AB  - BACKGROUND: Pregnant women who gain excess weight are at risk of complications
      during pregnancy and in the long term. Interventions based on diet and physical
      activity minimise gestational weight gain with varied effect on clinical
      outcomes. The effect of interventions on varied groups of women based on body
      mass index, age, ethnicity, socioeconomic status, parity, and underlying medical
      conditions is not clear. Our individual patient data (IPD) meta-analysis of
      randomised trials will assess the differential effect of diet- and physical
      activity-based interventions on maternal weight gain and pregnancy outcomes in
      clinically relevant subgroups of women. METHODS/DESIGN: Randomised trials on diet
      and physical activity in pregnancy will be identified by searching the following
      databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index,
      Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled
      Trials, Database of Abstracts of Reviews of Effects, and Health Technology
      Assessment Database. Primary researchers of the identified trials are invited to
      join the International Weight Management in Pregnancy Collaborative Network and
      share their individual patient data. We will reanalyse each study separately and
      confirm the findings with the original authors. Then, for each intervention type
      and outcome, we will perform as appropriate either a one-step or a two-step IPD
      meta-analysis to obtain summary estimates of effects and 95% confidence
      intervals, for all women combined and for each subgroup of interest. The primary
      outcomes are gestational weight gain and composite adverse maternal and fetal
      outcomes. The difference in effects between subgroups will be estimated and
      between-study heterogeneity suitably quantified and explored. The potential for
      publication bias and availability bias in the IPD obtained will be investigated.
      We will conduct a model-based economic evaluation to assess the cost
      effectiveness of the interventions to manage weight gain in pregnancy and
      undertake a value of information analysis to inform future research. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO 2013: CRD42013003804.

PMID- 25370507
TI  - Echocardiographic and electrocardiographic findings in patients with obesity
      hypoventilation syndrome.
AB  - BACKGROUND: Obesity is a risk factor for both sleep-related breathing disorders
      (SRBD), including obesity hypoventilation syndrome (OHS) and cardiovascular
      diseases (CVD). The development of CVD in patients with SRBD is usually
      attributed to the fact that most patients are obese in addition to conventional
      cardiovascular risk factors. AIMS: This study aims to measure the prevalence of
      certain CVD in patients with OHS in the Auckland region and highlight the
      importance of the effects of SRBD on the heart. METHODS: A dataset of all
      patients with a formal diagnosis of OHS that were under active follow up was
      compiled from Auckland District Health Board Sleep Disordered Breathing Service.
      Clinical notes were retrospectively reviewed for echocardiogram reports, blood
      pressure measurements and electrocardiograms. RESULTS: Forty-seven patients were
      included in the present study. The median age was 60 years, 24 were female (51%),
      20 (42.5%) had diabetes, mean HbA1C was 53.5 mmol/mol, mean systolic blood
      pressure was 127 mmHg, mean body mass index was 49 kg/m(2) , mean forced
      expiratory volume in 1 s was 1.7 L, mean estimated glomerular filtration was 71
      mL/min/1.73 m(2) and there was anti-hypertensive use in 31 (65.9%) patients.
      Thirty-three patients had poor quality echocardiography views (70.2%). Left
      ventricular systolic and diastolic function was impaired in 8 (25%) and 18 (60%)
      respectively. Right ventricular dysfunction and pulmonary hypertension was
      present in 19 (63.3%) and 13 (52%) respectively. Sixteen patients (34%) had
      recurrent atrial or ventricular arrhythmias. CONCLUSION: There appears to be a
      high prevalence of right ventricular impairment, pulmonary hypertension, left
      ventricle hypertrophy, diastolic dysfunction and arrhythmias in patients with
      OHS. These findings would appear to be higher than expected in obese patients
      without OHS. A larger prospective matched cohort study would be needed to confirm
      the clinical significance of these findings.

PMID- 25370508
TI  - In situ labelling chemistry of respiratory syncytial viruses by employing the
      biotinylated host-cell membrane protein for tracking the early stage of virus
      entry.
AB  - An in situ labelling strategy was proposed to produce quantum dot-labelled
      respiratory syncytial viruses (RSVs) by incorporating the biotinylated membrane
      protein of the host cells into mature virions, followed by conjugation with
      streptavidin modified quantum dots (SA-QDs), which has the advantages such as
      convenience, efficiency and minor influence on viral infectivity and thus could
      be successfully applied to track the early stage of virus entry. 

PMID- 25370509
TI  - Effects of mesenchymal stem/stromal cells on cultures of corneal epithelial
      progenitor cells with ethanol injury.
AB  - PURPOSE: Mesenchymal stem/stromal cells (MSCs) facilitate the regeneration of
      injured tissue. Our group has previously shown that human MSCs (hMSCs) or hMSC
      derived factors suppress excessive inflammatory response in the cornea following
      chemical injury in vivo. We here investigated direct effects of hMSC-derived
      factors on cultures of chemically injured human corneal epithelial progenitor
      cells (hCEP), independent of systemic anti-inflammatory effects that hMSCs have
      been shown to have in vivo. METHODS: We injured hCEP by incubation in 20% ethanol
      for 30 seconds, and cultured the cells in fresh medium or in medium derived from
      cultures of human dermal fibroblasts (hFbs), hMSCs, or TNF-alpha-activated hMSCs.
      After 24 hours, we evaluated the survival, proliferation, and apoptosis of the
      cells. RESULTS: The hMSC-conditioned medium enhanced survival and proliferation
      and inhibited apoptosis of chemically injured hCEP. In addition, the conditioned
      medium accelerated the wound healing of corneal epithelium in tissue cultures of
      rabbit corneas following injury. The effects of the hMSC-conditioned medium were
      increased by preincubating hMSCs with TNF-alpha. The increased effectiveness of
      the medium from the preactivated hMSCs was in part explained by increased
      concentration of the multifunctional protein stanniocalcin-1 that inhibits
      apoptosis and promotes survival of cells. CONCLUSIONS: Together, the data account
      for beneficial effects of hMSCs on tissue-endogenous stem cells involving hCEP,
      and provide a basis for using MSCs or MSC-derived factors to treat diseases of
      the cornea and other tissues.

PMID- 25370511
TI  - Contrast sensitivity and foveal microstructure following vitrectomy for
      epiretinal membrane.
AB  - PURPOSE: To evaluate contrast sensitivity (CS) in patients with epiretinal
      membrane (ERM) following vitrectomy and to investigate the relationship between
      CS and foveal microstructures with spectral-domain optical coherence tomography
      (SD-OCT). METHODS: Thirty-one eyes of 31 patients with ERM were included. We
      examined CS with a CSV-1000E chart, a logMAR best-corrected visual acuity (BCVA),
      and foveal microstructure by using SD-OCT before and at 6 months after surgery.
      From the CS data, the area under the log contrast sensitivity function (AULCSF)
      was calculated. Based on the OCT images, we quantified the mean thickness of the
      ganglion cell layer (GCL), the inner nuclear layer (INL), and the outer retinal
      layer (outer nuclear layer and outer plexiform layer [ONL+OPL]). The status of
      the photoreceptor inner and outer segment junction (IS/OS) and external limiting
      membrane (ELM) was also evaluated. RESULTS: Vitrectomy significantly improved
      logMAR BCVA and AULCSF. Even in patients with poor improvement of visual acuity
      (changes in logMAR BCVA by surgery was <=0.2), postoperative AULCSF significantly
      increased by treatment (P < 0.05). Postoperative AULCSF showed a significant
      correlation with preoperative (P < 0.05) and postoperative (P < 0.05) ONL+OPL
      thickness, whereas other parameters were not relevant. Postoperative logMAR BCVA
      significantly correlated with postoperative status of IS/OS (P < 0.05) and
      preoperative ONL+OPL thickness (P < 0.05). CONCLUSIONS: In patients with ERM, CS
      improved even though their visual acuity did not recover significantly by
      vitrectomy. CS was associated with the thickness of outer retinal layer.

PMID- 25370512
TI  - Chronic hypertension increases susceptibility to acute IOP challenge in rats.
AB  - PURPOSE: To consider the effect of chronic arterial hypertension on the
      susceptibility of the retina to acute IOP challenge. METHODS: Anesthetized adult
      Long-Evans rats with normal (n = 5, receiving saline subcutaneously), chronic
      high blood pressure (BP) for 4 weeks (n = 15, Angiotensin II subcutaneously), and
      acute high BP for 1 hour (n = 10, Angiotensin II intravenously) underwent IOP
      elevation (10-120 mm Hg, 5 mm Hg steps each 3 minutes). During IOP elevation,
      retinal function and ocular blood flow were monitored with electroretinogram
      (ERG) and laser-Doppler flowmetry (LDF), respectively. Blood pressure was
      monitored via a femoral artery cannula. Electroretinogram and LDF responses are
      expressed as a percentage of baseline and compared between groups. The left
      ventricle and the aorta were dissected to assess the morphologic changes
      associated with chronic hypertension. RESULTS: Four weeks of hypertension
      (systolic BP 192 +/- 4 mm Hg) produced cardiac hypertrophy and thickened aortic
      arterial walls compared with controls (systolic BP 112 +/- 3 mm Hg). Retinal
      function was unaltered with chronic hypertension compared with normotensive
      animals. During acute IOP elevation, ERG and LDF were reduced in a dose-dependent
      manner in all BP groups. Both chronic and acute hypertension made the ERG and LDF
      less susceptible to IOP elevation. However, the degree of resistance to IOP
      elevation was greater in acute hypertension compared with chronic hypertension (P
      < 0.05). CONCLUSIONS: Acute BP elevation makes retinal function and blood flow
      less susceptible to IOP elevation. The reduced susceptibility afforded by
      improved ocular perfusion pressure is compromised after 4 weeks of chronic
      hypertension.

PMID- 25370514
TI  - Visual impairment and the incidence of falls and fractures among older people:
      longitudinal findings from the Blue Mountains Eye Study.
AB  - PURPOSE: We assessed the impact of visual impairment on the incidence of falls
      and fractures in older persons. METHODS: Of 3654 baseline participants, 2334,
      1952, and 1149 were re-examined after 5, 10, and 15 years. Presenting visual
      acuity (VA) was measured at each examination. Bilateral and unilateral visual
      impairment was defined as VA worse than 20/40 in the better and worse eye,
      respectively. Incident visual impairment was defined in eyes with VA 20/40 or
      better at baseline, which subsequently developed visual impairment. Incidence of
      falls was assessed over the 12 months before each visit, whereas incidence of
      fractures was assessed over the 5 years between two visits. Discrete logistic
      regression models with time-dependent variables were used to assess associations
      between visual impairment and subsequent falls and fractures after adjusting for
      potential confounding variables. RESULTS: The proportions of participants
      reporting >=2 falls ranged between 10% and 14%, and proportions reporting
      fractures ranged between 12% and 21%, across the three follow-up visits.
      Participants with incident visual impairment were more likely to report >=2 falls
      in 5 years, OR (odds ratio) 1.46, 95% confidence interval (CI) 1.04 to 2.04
      (bilateral), and OR 1.22, 95% CI 0.98 to 1.51 (unilateral). Compared to
      participants with normal vision, those with incident unilateral visual impairment
      had a higher incidence of fractures over 5 years (OR, 1.27; 95% CI, 0.98-1.51).
      No increased incidence of falls or fractures was evident after 5+ years among
      participants with visual impairment. CONCLUSIONS: In this older cohort, recent
      development of visual impairment was associated with increased likelihood of
      subsequent falls and fractures in the next 5 years, independent of other
      confounding variables.

PMID- 25370516
TI  - Factors affecting plastic lamina cribrosa displacement in glaucoma patients.
AB  - PURPOSE: To investigate factors associated with irreversible components of
      anterior lamina cribrosa (LC) depth in glaucoma patients. METHODS: A total of 141
      glaucoma patients and 51 healthy control subjects were enrolled. The optic nerve
      head (ONH) was imaged using the enhanced depth imaging (EDI) modes of Spectralis
      optical coherence tomography (OCT). The depth of the LC was measured at the
      midhorizontal, superior, and inferior midperipheral regions of the ONH of each
      eye. Analyzed factors associated LC depth included age, axial length, intraocular
      pressure (IOP), disc size, central corneal thickness, average retinal nerve fiber
      layer (RNFL) thickness, and mean deviation (MD). RESULTS: In glaucoma patients,
      the LC was more deeply located compared with the control group at the
      midhorizontal and superior and inferior midperipheral B-scans (All P < 0.001).
      Age, initial IOP, and treated IOP was correlated with mean LC depth (All P <
      0.001), and those correlations remained after adjusting for MD and RNFL thickness
      (All P < 0.001). In multivariate analysis, younger age, high untreated IOP, and
      thinner RNFL thickness was significantly associated with a deeper LC (P = 0.015,
      <0.001, and 0.042). There was an interaction between age and MD as predictors for
      LC depth (P = 0.007). CONCLUSIONS: The anterior LC surface is more deeply located
      in glaucoma patients compared with healthy controls. In glaucoma patients, age,
      initial IOP, and RNFL thickness were influential factors related to LC depth.
      These factors should be considered in clinical application of plastic LC
      displacement in glaucoma patients.

PMID- 25370510
TI  - Baseline OCT measurements in the idiopathic intracranial hypertension treatment
      trial, part I: quality control, comparisons, and variability.
AB  - PURPOSE: Optical coherence tomography (OCT) has been used to investigate
      papilledema in single-site, mostly retrospective studies. We investigated whether
      spectral-domain OCT (SD-OCT), which provides thickness and volume measurements of
      the optic nerve head and retina, could reliably demonstrate structural changes
      due to papilledema in a prospective multisite clinical trial setting. METHODS: At
      entry, 126 subjects in the Idiopathic Intracranial Hypertension Treatment Trial
      (IIHTT) with mild visual field loss had optic disc and macular scans, using the
      Cirrus SD-OCT. Images were analyzed by using the proprietary commercial and
      custom 3D-segmentation algorithms to calculate retinal nerve fiber layer (RNFL),
      total retinal thickness (TRT), optic nerve head volume (ONHV), and retinal
      ganglion cell layer (GCL) thickness. We evaluated variability, with interocular
      comparison and correlation between results for both methods. RESULTS: The average
      RNFL thickness > 95% of normal controls in 90% of eyes and the RNFL, TRT, ONH
      height, and ONHV showed strong (r > 0.8) correlations for interocular
      comparisons. Variability for repeated testing of OCT parameters was low for both
      methods and intraclass correlations > 0.9 except for the proprietary GCL
      thickness. The proprietary algorithm-derived RNFL, TRT, and GCL thickness
      measurements had failure rates of 10%, 16%, and 20% for all eyes respectively,
      which were uncommon with 3D-segmentation-derived measurements. Only 7% of eyes
      had GCL thinning that was less than fifth percentile of normal age-matched
      control eyes by both methods. CONCLUSIONS: Spectral-domain OCT provides reliable
      continuous variables and quantified assessment of structural alterations due to
      papilledema. (ClinicalTrials.gov number, NCT01003639.).

PMID- 25370515
TI  - Regional choroidal blood flow and multifocal electroretinography in experimental
      glaucoma in rhesus macaques.
AB  - PURPOSE: To test a hypothesis of regional variation in the effect of experimental
      glaucoma on choroidal blood flow (ChBF) and retinal function. METHODS: Five
      rhesus macaques underwent laser trabecular destruction (LTD) to induce elevated
      intraocular pressure (IOP). Intraocular pressures were elevated for 56 to 57
      weeks. Multifocal electroretinographic (mfERG) and multifocal visual evoked
      cortical potential (mfVEP) testing were performed at regular intervals before and
      during the period of IOP elevation. At euthanasia, the IOP was manometrically
      controlled at 35 (experimentally glaucomatous eye) and 15 (fellow control eye) mm
      Hg. Fluorescent microspheres were injected into the left ventricle. Regional ChBF
      was determined. RESULTS: All of the experimentally glaucomatous eyes exhibited
      supranormal first-order kernel (K1) root mean square (RMS) early portions of the
      mfERG waveforms and decreased amplitudes of the late waveforms. The
      supranormality was somewhat greater in the central macula. Second-order kernel,
      first slice (K2.1) RMS mfVEP response was inversely correlated (R(2) = 0.97) with
      axonal loss. Total ChBF was reduced in the experimentally glaucomatous eyes. The
      mean blood flow was 893 +/- 123 and 481 +/- 37 MUL/min in the control and
      glaucomatous eyes, respectively. The ChBF showed regional variability with the
      greatest proportional decrement most often found in the central macula.
      CONCLUSIONS: This is the first demonstration of globally reduced ChBF in chronic
      experimental glaucoma in the nonhuman primate. Both the alteration of mfERG
      waveform components associated with outer retinal function and the reduction in
      ChBF were greatest in the macula, suggesting that there may be a spatial
      colocalization between ChBF and some outer retinal effects in glaucoma.

PMID- 25370517
TI  - Spatiotemporal interactions in the visual cortex following paired electrical
      stimulation of the retina.
AB  - PURPOSE: Retinal prostheses use spatiotemporal patterns of electrical stimulation
      across multiple electrodes to provide visual percepts to blind patients. It is
      generally assumed that percepts produced by individual electrodes are independent
      of one another, which may not be the case. In this study, we aimed to quantify
      interactions between pairs of electrical stimuli delivered to the retina.
      METHODS: Normally sighted cats were implanted with a suprachoroidal electrode
      array. The retina was stimulated with a paired-pulse paradigm that consisted of a
      conditioning stimulus followed by a test stimulus, while recording multiunit
      activity in the visual cortex. Conditioning current, and spatial and temporal
      separation between the conditioning and test stimuli were varied. Cortical
      interactions were quantified by changes in multiunit activity elicited by
      stimulation with the paired-pulse paradigm, compared to stimulation of the test
      stimulus alone (control). RESULTS: Interactions varied as a function of
      conditioning current and temporal separation between the two stimulating pulses.
      Cortical activity increased compared to the control condition at an interstimulus
      delay of 1.025 ms and was significantly suppressed for delays between 20 and 90
      ms, returning to near control levels for longer delays. The level of interactions
      increased when the conditioning current was increased. Interactions were found to
      be similar for electrode separations up to 3 mm. CONCLUSIONS: Interactions
      between sequential stimulation of pairs of electrodes in a suprachoroidal retinal
      prosthesis occur for delays up to 100 ms and electrode separations of several
      millimeters. Knowledge of these spatiotemporal interactions is essential for
      developing effective patterns of stimulation for retinal prostheses.

PMID- 25370513
TI  - Baseline OCT measurements in the idiopathic intracranial hypertension treatment
      trial, part II: correlations and relationship to clinical features.
AB  - PURPOSE: The accepted method to evaluate and monitor papilledema, Frisen grading,
      uses an ordinal approach based on descriptive features. Part I showed that
      spectral-domain optical coherence tomography (SD-OCT) in a clinical trial setting
      provides reliable measurement of the effects of papilledema on the optic nerve
      head (ONH) and peripapillary retina, particularly if a 3-D segmentation method is
      used for analysis.(1) We evaluated how OCT parameters are interrelated and how
      they correlate with vision and other clinical features in idiopathic intracranial
      hypertension (IIH) patients. METHODS: A total of 126 subjects in the IIH
      Treatment Trial (IIHTT) OCT substudy had Cirrus SD-OCT optic disc and macula
      scans analyzed by using a 3-D segmentation algorithm to derive retinal nerve
      fiber layer (RNFL) thickness, total retinal thickness (TRT), retinal ganglion
      cell layer plus inner plexiform layer (GCL+IPL) thickness, and ONH volume. The SD
      OCT parameter values were correlated with high- and low-contrast acuity,
      perimetric mean deviation, Frisen grading, and IIH features. RESULTS: At study
      entry, the average RNFL thickness, TRT, and ONH volume showed significant strong
      correlations (r >= 0.90) with each other. The same OCT parameters showed a strong
      (r > 0.76) correlation with Frisen grade and a mild (r > 0.24), but significant,
      correlation with lumbar puncture opening pressure. For all eyes at baseline,
      neither visual acuity (high or low contrast) nor mean deviation correlated with
      any OCT measure of swelling or GCL+IPL thickness. CONCLUSIONS: In newly diagnosed
      IIH, OCT demonstrated alterations of the peripapillary retina and ONH correlate
      with Frisen grading of papilledema. At presentation, OCT measures of papilledema,
      in patients with newly diagnosed IIH and mild vision loss, do not correlate with
      clinical features or visual dysfunction. (ClinicalTrials.gov number,
      NCT01003639.).

PMID- 25370518
TI  - Solar UV radiation-induced DNA Bipyrimidine photoproducts: formation and
      mechanistic insights.
AB  - This review chapter presents a critical survey of the main available information
      on the UVB and UVA bipyrimidine photoproducts which constitute the predominant
      recipient classes of photo-induced DNA damage. Evidence is provided that UVB
      irradiation of isolated DNA in aqueous solutions and in cells gives rise to the
      predominant generation of cis-syn cyclobutane pyrimidine dimers (CPDs) and, to a
      lesser extent, of pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), the
      importance of which is strongly primary sequence dependent. A notable change in
      the photoproduct distribution is observed when DNA either in the dry or in
      desiccated microorganisms is exposed to UVC or UVB photons with an overwhelming
      formation of 5-(alpha-thymidyl)-5,6-dihydrothymidine, also called spore
      photoproduct (dSP), at the expense of CPDs and 6-4PPs. UVA irradiation of
      isolated and cellular DNA gives rise predominantly to bipyrimidine photoproducts
      with the overwhelming formation of thymine-containing cyclobutane pyrimidine
      dimers at the exclusion of 6-4PPs. UVA photons have been shown to modulate the
      distribution of UVB dimeric pyrimidine photoproducts by triggering isomerization
      of the 6-4PPs into related Dewar valence isomers. Mechanistic aspects of the
      formation of bipyrimidine photoproducts are discussed in the light of recent
      photophysical and theoretical studies. 

PMID- 25370519
TI  - Carbon-hydrogen to carbon-phosphorus transformations.
AB  - Literature published between 2008 and 2013 concerning the functionalization of
      carbon-hydrogen into carbon-phosphorus bonds is surveyed. The chapter is
      organized by reaction mechanism. The majority of methods still proceed via
      deprotonation of C-H into C-M (M=Li, Na, etc.) followed by reaction with a
      phosphorus electrophile P-X, where X is usually chlorine. A few examples of
      electrophilic aromatic substitution and related processes have also been
      reported, although this approach has not yet been developed significantly. Over
      the past 5 years a rapidly growing family of reactions includes transition metal
      "C-H activation" and formally related radical-based processes has been developed.
      The latter processes offer exciting prospects for the synthesis of
      organophosphorus compounds.

PMID- 25370520
TI  - Recent advances in H-phosphonate chemistry. Part 1. H-phosphonate esters:
      synthesis and basic reactions.
AB  - This review covers recent progress in the preparation of H-phosphonate mono- and
      diesters, basic studies on mechanistic and stereochemical aspects of this class
      of phosphorus compounds, and their fundamental chemistry in terms of
      transformation of P-H bonds into P-heteroatom bonds. Selected recent applications
      of H-phosphonate derivatives in basic organic phosphorus chemistry and in the
      synthesis of biologically important phosphorus compounds are also discussed. 

PMID- 25370521
TI  - Phosphinic peptides as potent inhibitors of zinc-metalloproteases.
AB  - The development of transition-state analogs is a major objective in enzymology,
      not only for developing potent inhibitors of enzymes but also for dissecting
      enzyme catalytic mechanisms. Phosphinic peptides, which share closed structural
      similarities with the transition-state of peptide substrate upon hydrolysis, have
      thus been considered for identifying potent inhibitors of proteases. Focusing on
      the zinc-proteases family, this review presents the most important synthetic
      efforts performed to obtain the desired compounds. Crystal structures of the
      phosphinic peptides in interaction with their zinc-protease targets are reported
      to illustrate the structural features which may explain the potency of these
      compounds and how they contribute to uncover key enzyme catalytic residues. Based
      on a remarkable metabolic stability, phosphinic peptides can be used to probe the
      in vivo function of zinc-proteases. Progress on chemistry and better
      understanding on the functional roles of zinc-proteases should allow transferring
      these compounds from shelf to clinic. 

PMID- 25370522
TI  - Peptide Thioester Formation via an Intramolecular N to S Acyl Shift for Peptide
      Ligation.
AB  - In chemical protein synthesis, peptide building blocks are prepared by solid
      phase peptide synthesis (SPPS), and then connected by chemical ligation methods.
      The peptide thioester is one of key building blocks used in chemical protein
      synthesis, and improvements in the Fmoc SPPS procedure for preparing such
      thioesters would be highly desirable. In this review we focus on a method for
      peptide thioester synthesis based on the use of an intramolecular N to S acyl
      shift reaction as a key reaction. Amide and thioester forms at the thiol
      containing residue are in equilibrium as a result of a reversible intramolecular
      acyl shift, which is detectable by 13C NMR. The amide form is favored under
      neutral conditions, while the thioester predominates under acidic conditions.
      Thiol auxiliaries can be employed to facilitate the formation of a thioester from
      an amide via an intramolecular N-S acyl shift, and the peptide thioester is
      formed after intermolecular transthioesterification in the presence of excess
      amounts of thiols. Even under neutral conditions, thiol auxiliary-containing
      peptides can be ligated with a cysteinyl peptide via an intramolecular N-S acyl
      shift, followed by native chemical ligation (NCL) in a one-pot reaction. These
      procedures can be applied to the chemical synthesis of proteins which are post
      translationally modified.

PMID- 25370523
TI  - Peptide fragmentation products in mass spectrometry probed by infrared
      spectroscopy.
AB  - Vibrational spectroscopy offers detailed insights, by virtue of diagnostic
      infrared bands, into the chemical structures and moieties which are formed during
      peptide fragmentation inside mass spectrometers. Over the past few years, IRMPD
      spectroscopy has led to a greatly improved understanding of the chemistry that
      takes place during collision-induced dissociation (CID) of protonated peptides.
      For instance, the rearrangement chemistry of b- and a-type ions, which is
      relevant in sequence scrambling pathways, has been directly confirmed with the
      technique. In this chapter, we provide a brief background on peptide
      fragmentation chemistry, and give an overview of areas where vibrational
      spectroscopy has been successfully implemented, such as CID of protonated and de
      protonated peptides. We also discuss the potential of the technique for
      elucidating lesser-studied radical dissociation processes, such as electron
      capture dissociation (ECD), electron transfer dissociation (ETD), and laser
      photodissociation. 

PMID- 25370524
TI  - I-motif-based nano-flares for sensing pH changes in live cells.
AB  - Here, we report an intracellular probe termed i-motif-based nano-flares. They
      could sense pH change in a live cell since they combine cellular transfection,
      enzymatic protection, and pH detection. 

PMID- 25370525
TI  - Nuclear cupping in the blasts-more to the cup than myeloid.

PMID- 25370526
TI  - Purse-string double-layer closure: a novel technique for repairing the uterine
      incision during cesarean section.
AB  - AIM: To compare the classical double-layer uterine closure to a double-layer
      purse-string uterine closure (Turan technique) in cesarean section regarding
      short- and long-term results. METHODS: Patients were randomized into either the
      double-layer purse-string uterine closure arm (study group, 84 patients) or the
      classical double-layer uterine closure arm (control group, 84 patients). For
      short-term comparison, a detailed transvaginal ultrasound examination was planned
      in all patients 6 weeks after the operation and a wedge-shaped defect in the
      uterine incision scar was accepted as uterine scar defect and recorded. For the
      long-term comparison, subsequent pregnancies of these patients were followed up
      for any complication. RESULTS: The number of patients with ultrasonographically
      visible uterine scar defect was 12 (23.5% of all scar defects) in the study group
      whereas it was 39 (76.5% of all scar defects) in the control group (P < 0.001,
      chi(2) = 15.42). Demographic data, operation time, hospitalization time,
      preoperative and postoperative hemoglobin values were not significantly different
      between the groups. During the 2-year of the follow-up period, five patients in
      the study group and six patients in the control group became pregnant again. No
      complication during their pregnancies and second cesarean operation were
      encountered. CONCLUSION: With the Turan technique, the uterine incision length
      becomes shorter, and the frequency of uterine scar defect is lower regarding
      short-term results. More data is needed for long-term results. ClinicalTrials.gov
      NCT01287611.

PMID- 25370527
TI  - Periocular intralymphatic histiocytosis or localized Melkersson-Rosenthal
      syndrome?
AB  - We describe three cases of periocular edema with histopathologic features of
      intralymphatic histiocytosis without extravascular granulomas. All were elderly
      males with no other significant medical problems. Previous reports of periocular
      Melkersson-Rosenthal syndrome are identical clinically, and some reports show
      illustrations of intralymphatic histiocytosis histopathologically, in addition to
      other features typical of the syndrome. Given the lack of associated diseases or
      other features of the Melkersson-Rosenthal triad, some of these cases may be
      better defined as periocular intralymphatic histiocytosis. 

PMID- 25370529
TI  - Mud volcanoes of trinidad as astrobiological analogs for martian environments.
AB  - Eleven onshore mud volcanoes in the southern region of Trinidad have been studied
      as analog habitats for possible microbial life on Mars. The profiles of the 11
      mud volcanoes are presented in terms of their physical, chemical, mineralogical,
      and soil properties. The mud volcanoes sampled all emitted methane gas
      consistently at 3% volume. The average pH for the mud volcanic soil was 7.98. The
      average Cation Exchange Capacity (CEC) was found to be 2.16 kg/mol, and the
      average Percentage Water Content was 34.5%. Samples from three of the volcanoes,
      (i) Digity; (ii) Piparo and (iii) Devil's Woodyard were used to culture bacterial
      colonies under anaerobic conditions indicating possible presence of methanogenic
      microorganisms. The Trinidad mud volcanoes can serve as analogs for the Martian
      environment due to similar geological features found extensively on Mars in
      Acidalia Planitia and the Arabia Terra region. 

PMID- 25370528
TI  - Biota and biomolecules in extreme environments on Earth: implications for life
      detection on Mars.
AB  - The three main requirements for life as we know it are the presence of organic
      compounds, liquid water, and free energy. Several groups of organic compounds
      (e.g., amino acids, nucleobases, lipids) occur in all life forms on Earth and are
      used as diagnostic molecules, i.e., biomarkers, for the characterization of
      extant or extinct life. Due to their indispensability for life on Earth, these
      biomarkers are also prime targets in the search for life on Mars. Biomarkers
      degrade over time; in situ environmental conditions influence the preservation of
      those molecules. Nonetheless, upon shielding (e.g., by mineral surfaces),
      particular biomarkers can persist for billions of years, making them of vital
      importance in answering questions about the origins and limits of life on early
      Earth and Mars. The search for organic material and biosignatures on Mars is
      particularly challenging due to the hostile environment and its effect on organic
      compounds near the surface. In support of life detection on Mars, it is crucial
      to investigate analogue environments on Earth that resemble best past and present
      Mars conditions. Terrestrial extreme environments offer a rich source of
      information allowing us to determine how extreme conditions affect life and
      molecules associated with it. Extremophilic organisms have adapted to the most
      stunning conditions on Earth in environments with often unique geological and
      chemical features. One challenge in detecting biomarkers is to optimize
      extraction, since organic molecules can be low in abundance and can strongly
      adsorb to mineral surfaces. Methods and analytical tools in the field of life
      science are continuously improving. Amplification methods are very useful for the
      detection of low concentrations of genomic material but most other organic
      molecules are not prone to amplification methods. Therefore, a great deal depends
      on the extraction efficiency. The questions "what to look for", "where to look",
      and "how to look for it" require more of our attention to ensure the success of
      future life detection missions on Mars. 

PMID- 25370530
TI  - Compartmentalization and Cell Division through Molecular Discreteness and
      Crowding in a Catalytic Reaction Network.
AB  - Explanation of the emergence of primitive cellular structures from a set of
      chemical reactions is necessary to unveil the origin of life and to
      experimentally synthesize protocells. By simulating a cellular automaton model
      with a two-species hypercycle, we demonstrate the reproduction of a localized
      cluster; that is, a protocell with a growth-division process emerges when the
      replication and degradation speeds of one species are respectively slower than
      those of the other species, because of overcrowding of molecules as a natural
      outcome of the replication. The protocell exhibits synchrony between its division
      process and replication of the minority molecule. We discuss the effects of the
      crowding molecule on the formation of primitive structures. The generality of
      this result is demonstrated through the extension of our model to a hypercycle
      with three molecular species, where a localized layered structure of molecules
      continues to divide, triggered by the replication of a minority molecule at the
      center. 

PMID- 25370532
TI  - Effect of elevated CO2 concentration on photosynthetic characteristics of
      hyperaccumulator Sedum alfredii under cadmium stress.
AB  - The combined effects of elevated CO2 and cadmium (Cd) on photosynthetic rate,
      chlorophyll fluorescence and Cd accumulation in hyperaccumulator Sedum alfredii
      Hance were investigated to predict plant growth under Cd stress with rising
      atmospheric CO2 concentration. Both pot and hydroponic experiments were conducted
      and the plants were grown under ambient (350 uL L(-1)) or elevated (800 uL L(-1))
      CO2 . Elevated CO2 significantly (P < 0.05) increased Pn (105%-149%), Pnmax
      (38.8%-63.0%) and AQY (20.0%-34.8%) of S. alfredii in all the Cd treatments, but
      reduced chlorophyll concentration, dark respiration and photorespiration. After
      10 days growth in medium with 50 uM Cd under elevated CO2 , PSII activities were
      significantly enhanced (P < 0.05) with Pm, Fv/Fm, Phi(II) and qP increased by
      66.1%, 7.5%, 19.5% and 16.4%, respectively, as compared with ambient-grown
      plants. Total Cd uptake in shoot of S. alfredii grown under elevated CO2 was
      increased by 44.1%-48.5%, which was positively correlated with the increase in
      Pn. These results indicate that elevated CO2 promoted the growth of S. alfredii
      due to increased photosynthetic carbon uptake rate and photosynthetic light-use
      efficiency, and showed great potential to improve the phytoextraction of Cd by S.
      alfredii.

PMID- 25370531
TI  - Synergism and mutualism in non-enzymatic RNA polymerization.
AB  - The link between non-enzymatic RNA polymerization and RNA self-replication is a
      key step towards the "RNA world" and still far from being solved, despite
      extensive research. Clay minerals, lipids and, more recently, peptides were found
      to catalyze the non-enzymatic synthesis of RNA oligomers. Herein, a review of the
      main models for the formation of the first RNA polymers is presented in such a
      way as to emphasize the cooperation between life's building blocks in their
      emergence and evolution. A logical outcome of the previous results is a
      combination of these models, in which RNA polymerization might have been
      catalyzed cooperatively by clays, lipids and peptides in one multi-component
      prebiotic soup. The resulting RNAs and oligopeptides might have mutualistically
      evolved towards functional RNAs and catalytic peptides, preceding the first RNA
      replication, thus supporting an RNA-peptide world. The investigation of such a
      system is a formidable challenge, given its complexity deriving from a
      tremendously large number of reactants and innumerable products. A rudimentary
      experimental design is outlined, which could be used in an initial attempt to
      study a quaternary component system. 

PMID- 25370533
TI  - PD-L1 expression in melanocytic lesions does not correlate with the BRAF V600E
      mutation.
AB  - PD-L1 expression in melanoma correlates with response to PD-1 pathway-blocking
      antibodies. Aberrant tumor-cell PD-L1 expression may be oncogene driven and/or
      induced by IFNgamma. Melanomas express PD-L1 in association with tumor
      infiltrating lymphocytes (TIL), but the potential contribution of the BRAF V600E
      mutation (BRAFmut) to induced PD-L1 expression has not been determined. Fifty-two
      archival melanocytic lesions were assessed for PD-L1 expression, TIL
      infiltration, and BRAFmut simultaneously. IFNgamma-induced PD-L1 expression in
      cultured melanomas was assessed in parallel according to BRAF status. Melanocyte
      PD-L1 expression was observed in 40% of specimens, and BRAFmut was observed in
      42% of specimens, but no significant concordance was found between these
      variables. Almost all melanocytes displaying PD-L1 expression were observed to be
      adjacent to TILs, irrespective of BRAF status. TIL(-) lesions were not more
      likely to be associated with BRAFmut, when compared with TIL(+) lesions. Baseline
      expression of PD-L1 by melanoma cell lines was virtually nil, regardless of
      BRAFmut status, and the intensity of IFN-induced PD-L1 expression in melanoma
      cell lines likewise did not correlate with BRAF mutational status. PD-L1
      expression in melanocytic lesions does not correlate with the BRAFmut. Thus,
      distinct populations of melanoma patients will likely benefit from BRAF
      inhibitors versus PD-1 pathway blockade.

PMID- 25370535
TI  - One-handed single helicates of dinickel(II) benzenehexapyrrole-alpha,omega
      diimine with an amine chiral source.
AB  - Benzenehexapyrrole-alpha,omega-dialdehyde, composed of a pair of formyltripyrrole
      units with a 1,3-phenylene linker, was metallated to give dinuclear single
      stranded helicates. X-ray studies of the bis-nickel(II) complex showed a helical
      C2 form with a pair of helical-metal coordination planes of a 3N+O donor set. The
      terminal aldehyde was readily converted into the imine by optically active
      amines, whereby helix-sense bias was induced. Bis-nickel(II) and bis
      palladium(II) complexes of the benzenehexapyrrole-alpha,omega-diimines were
      studied to show that an enantiomer pair of the helical C2 form are interchanged
      by slow flipping of each coordination plane and fast rotation around the
      C(benzene)?C(pyrrole) bond. The helical screw in the bis-nickel(II) complexes was
      biased to one side in more than 95 % diastereoselectivity, which was achieved by
      using a variety of optically active amines, such as (R)-1-cyclohexylethylamine,
      (S)-1- phenylethylamine, L-Phe(OEt) (Phe=phenylalanine), and (R)-valinol. The
      nickel complexes showed much better diastereoselectivity than the corresponding
      palladium complexes. 

PMID- 25370534
TI  - Tasquinimod modulates suppressive myeloid cells and enhances cancer
      immunotherapies in murine models.
AB  - A major barrier for cancer immunotherapy is the presence of suppressive cell
      populations in patients with cancer, such as myeloid-derived suppressor cells
      (MDSC) and tumor-associated macrophages (TAM), which contribute to the
      immunosuppressive microenvironment that promotes tumor growth and metastasis.
      Tasquinimod is a novel antitumor agent that is currently at an advanced stage of
      clinical development for treatment of castration-resistant prostate cancer. A
      target of tasquinimod is the inflammatory protein S100A9, which has been
      demonstrated to affect the accumulation and function of tumor-suppressive myeloid
      cells. Here, we report that tasquinimod provided a significant enhancement to the
      antitumor effects of two different immunotherapeutics in mouse models of cancer:
      a tumor vaccine (SurVaxM) for prostate cancer and a tumor-targeted superantigen
      (TTS) for melanoma. In the combination strategies, tasquinimod inhibited distinct
      MDSC populations and TAMs of the M2-polarized phenotype (CD206(+)). CD11b(+)
      myeloid cells isolated from tumors of treated mice expressed lower levels of
      arginase-1 and higher levels of inducible nitric oxide synthase (iNOS), and were
      less immunosuppressive ex vivo, which translated into a significantly reduced
      tumor-promoting capacity in vivo when these cells were coinjected with tumor
      cells. Tumor-specific CD8(+) T cells were increased markedly in the circulation
      and in tumors. Furthermore, T-cell effector functions, including cell-mediated
      cytotoxicity and IFNgamma production, were potentiated. Taken together, these
      data suggest that pharmacologic targeting of suppressive myeloid cells by
      tasquinimod induces therapeutic benefit and provide the rationale for clinical
      testing of tasquinimod in combination with cancer immunotherapies.

PMID- 25370536
TI  - Design and rationale of the comprehensive evaluation of risk factors in older
      patients with AMI (SILVER-AMI) study.
AB  - BACKGROUND: While older adults (age 75 and over) represent a large and growing
      proportion of patients with acute myocardial infarction (AMI), they have
      traditionally been under-represented in cardiovascular studies. Although
      chronological age confers an increased risk for adverse outcomes, our current
      understanding of the heterogeneity of this risk is limited. The Comprehensive
      Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study was
      designed to address this gap in knowledge by evaluating risk factors (including
      geriatric impairments, such as muscle weakness and cognitive impairments) for
      hospital readmission, mortality, and health status decline among older adults
      hospitalized for AMI. METHODS/DESIGN: SILVER-AMI is a prospective cohort study
      that is enrolling 3000 older adults hospitalized for AMI from a recruitment
      network of approximately 70 community and academic hospitals across the United
      States. Participants undergo a comprehensive in-hospital assessment that includes
      clinical characteristics, geriatric impairments, and health status measures.
      Detailed medical record abstraction complements the assessment with diagnostic
      study results, in-hospital procedures, and medications. Participants are
      subsequently followed for six months to determine hospital readmission,
      mortality, and health status decline. Multivariable regression will be used to
      develop risk models for these three outcomes. DISCUSSION: SILVER-AMI will fill
      critical gaps in our understanding of AMI in older patients. By incorporating
      geriatric impairments into our understanding of post-AMI outcomes, we aim to
      create a more personalized assessment of risk and identify potential targets for
      interventions. TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER: NCT01755052 .

PMID- 25370538
TI  - Head injury, alpha-synuclein genetic variability and Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Head injury has been linked to Parkinson's disease (PD)
      in some but not all studies. Differences in the genetic and environmental
      susceptibility to PD between populations might be one explanation. The joint
      effects of head injuries and SNCA genetic variants were investigated. METHODS:
      From 2001 to 2012, 561 incident idiopathic PD cases and 721 population controls
      from central California were enrolled. Subjects reported on head injuries
      throughout their lifetime and were assessed for genetic variability in the SNCA
      5' region (D4S3481; Rep1) and 3' untranslated region (rs356165). In unconditional
      logistic regression models adjusted for confounders, interactions between head
      injuries and genetic risk variants were investigated. RESULTS: Parkinson's
      disease risk in individuals with head injury who are carriers of at least one 263
      bp allele in D4S3481 or rs356165 variants was 3-4.5-fold higher compared with non
      carriers without head injuries. However, tests for interaction between head
      injury and SNCA D4S3481or rs356165 were not statistically significant.
      CONCLUSIONS: Our study finds some evidence that head injury and D4S3481 or
      rs356165 variants jointly increase the risk of PD but little evidence of
      interaction.

PMID- 25370539
TI  - When status is grabbed and when status is granted: Getting ahead in dominance and
      prestige hierarchies.
AB  - What type of behaviour affords status, agentic, or communal? Research to date has
      yielded inconsistent answers. In particular, the conflict view holds that agentic
      behaviour permits the imperious to grab status through overt force, whereas the
      functional view holds that communal behaviour permits the talented to earn status
      through popular appeal. Here, we synthesize both views by taking into account the
      moderating role played by group hierarchy. Group hierarchy can range from being
      dominance based (where status is grabbed) to prestige based (where status is
      granted). In a field study (Study 1), and a laboratory experiment (Study 2), we
      demonstrate that in different groups, status can be achieved in different ways.
      Specifically, agentic behaviour promotes status regardless of hierarchy type,
      whereas the effect of communal behaviour on status is moderated by hierarchy
      type: it augments it in more prestige-based hierarchies but diminishes it in more
      dominance-based hierarchies. 

PMID- 25370540
TI  - Family caregiving in India: importance of need-based support and intervention in
      acute care settings.

PMID- 25370541
TI  - Development and validation of a new bariatric-specific health-related quality of
      life instrument ''bariatric and obesity-specific survey (BOSS)''.
AB  - BACKGROUND: There is a lack of a psychometrically robust bariatric-specific
      health-related quality of life (HRQOL) tool. AIM: A single centre, prospective
      study to develop and validate a new bariatric-specific 81-item self-report HRQOL
      instrument called the Bariatric and Obesity-Specific Survey (BOSS). MATERIALS AND
      METHODS: Data were collected from 236 participants. Of these 83 patients were
      under consideration for bariatric surgery (Group 1) 68 patients had undergone a
      bariatric procedure (Group 2) and 85 normal healthy participants (Group 3). At
      baseline, participants were asked to complete the Short Form Health survey (SF
      36), Hospital Anxiety and Depression (HADS) scale, Moorehead-Ardelt Quality of
      life Questionnaire (M-A QoLQ II), and a demographic data sheet. Two weeks
      following the completion of these five questionnaires, participants were asked to
      complete BOSS once more along with a feedback sheet. RESULTS: Exploratory factor
      analysis revealed a multidimensional instrument consisting of 42 items
      distributed over six domains that addressed various HRQOL aspects and dimensions
      pertinent to bariatric surgery, and relevant to morbidly obese patients. Further
      psychometric analysis showed that BOSS has adequate internal consistency
      reliability (Cronbach alpha = 0.970), test re-test reliability (ICC = 0.926),
      construct validity, criterion validity, face validity and acceptability.
      CONCLUSION: BOSS thus appears to be a valid and reliable multidimensional
      instrument that provides a clinically useful and relevant measure to assess HRQOL
      in patients undergoing bariatric surgery.

PMID- 25370542
TI  - Reporting of various methodological and statistical parameters in negative
      studies published in prominent Indian Medical Journals: a systematic review.
AB  - OBJECTIVES: Biased negative studies not only reflect poor research effort but
      also have an impact on 'patient care' as they prevent further research with
      similar objectives, leading to potential research areas remaining unexplored.
      Hence, published 'negative studies' should be methodologically strong. All
      parameters that may help a reader to judge validity of results and conclusions
      should be reported in published negative studies. There is a paucity of data on
      reporting of statistical and methodological parameters in negative studies
      published in Indian Medical Journals. The present systematic review was designed
      with an aim to critically evaluate negative studies published in prominent Indian
      Medical Journals for reporting of statistical and methodological parameters.
      DESIGN: Systematic review. MATERIALS AND METHODS: All negative studies published
      in 15 Science Citation Indexed (SCI) medical journals published from India were
      included in present study. Investigators involved in the study evaluated all
      negative studies for the reporting of various parameters. Primary endpoints were
      reporting of "power" and "confidence interval." RESULTS: Power was reported in
      11.8% studies. Confidence interval was reported in 15.7% studies. Majority of
      parameters like sample size calculation (13.2%), type of sampling method (50.8%),
      name of statistical tests (49.1%), adjustment of multiple endpoints (1%), post
      hoc power calculation (2.1%) were reported poorly. Frequency of reporting was
      more in clinical trials as compared to other study designs and in journals having
      impact factor more than 1 as compared to journals having impact factor less than
      1. CONCLUSION: Negative studies published in prominent Indian medical journals do
      not report statistical and methodological parameters adequately and this may
      create problems in the critical appraisal of findings reported in these journals
      by its readers.

PMID- 25370543
TI  - Pre-injury neuro-psychiatric medication use, alone or in combination with cardiac
      medications, may affect outcomes in trauma patients.
AB  - BACKGROUND: Recent review of older (>=45-years-old) patients admitted to our
      trauma center showed that more than one-third were using neuro-psychiatric
      medications (NPMs) prior to their injury-related admission. Previously published
      data suggests that use of NPMs may increase patients' risk and severity of
      injury. We sought to examine the impact of pre-injury NPM use on older trauma
      patients' morbidity and mortality. MATERIALS AND METHODS: Retrospective record
      review included medication regimen characteristics and NPM use (antidepressants
      AD, antipsychotics-AP, anxiolytics-AA). Hospital morbidity, mortality, and 90-day
      survival were examined. Comparisons included regimens involving NPMs, further
      focusing on their interactions with various cardiac medications (beta blocker -
      BB; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker -
      ACE/ARB; calcium channel blocker - CCB). RESULTS: 712 patient records were
      reviewed (399 males, mean age 63.5 years, median ISS 8). 245 patients were taking
      at least 1 NPM: AD (158), AP (35), or AA (108) before injury. There was no effect
      of NPM monotherapy on hospital mortality. Patients taking >=3 NPMs had
      significantly lower 90-day survival compared to patients taking <=2 NPMs (81% for
      3 or more NPMs, 95% for no NPMs, and 89% 1-2 NPMs, P < 0.01). Several AD-cardiac
      medication (CM) combinations were associated with increased mortality compared to
      monotherapy with either agent (BB-AD 14.7% mortality versus 7.0% for AD
      monotherapy or 4.8% BB monotherapy, P < 0.05). Combinations of ACE/ARB-AA were
      associated with increased mortality compared to ACE/ARB monotherapy (11.5% vs
      4.9, P = 0.04). Finally, ACE/ARB-AD co-administration had higher mortality than
      ACE/ARB monotherapy (13.5% vs 4.9%, P = 0.01). CONCLUSIONS: Large proportion of
      older trauma patients was using pre-injury NPMs. Several regimens involving NPMs
      and CMs were associated with increased in-hospital mortality. Additionally, use
      of >=3 NPMs was associated with lower 90-day survival.

PMID- 25370544
TI  - Cardiac pathology in chronic alcoholics: a preliminary study.
AB  - BACKGROUND: Ethyl alcohol exerts both positive and negative effects on the
      cardiovascular system. Alcoholic cardiomyopathy, produced by direct or indirect
      mechanisms, is well-documented. An important, but seldom appreciated effect is an
      increase in iron deposition in the myocardium, which can add to the cardiac
      dysfunction. The present study was planned to document the pathological features
      and iron levels in the cardiac tissue of patients who were chronic alcoholics and
      correlate these characteristics with the liver pathology and iron content.
      MATERIALS AND METHODS: An autopsy-based prospective study of 40 consecutive
      patients compared with ten age matched controls (no history of alcohol intake).
      Histopathological changes like the morphology of the cardiac myocytes, degree of
      fibrosis (interstitial, interfiber, perivascular, and replacement), presence of
      inflammatory cells, increased capillary network, and adipose tissue deposition
      were noted and graded. These were also correlated with the liver pathology. The
      iron content in the heart and liver were measured by using calorimetry. RESULTS:
      All cases had increased epicardial adipose tissue with epicardial and endocardial
      fibrosis, prominence of interstitial and interfiber fibrosis, myofiber
      degeneration, and increased capillary network; this was particularly prominent in
      patients with cirrhosis. Elemental iron level in heart tissue was raised in the
      cases relative to controls. CONCLUSIONS: Alcohol produces subclinical changes in
      the myocardium, with an increased iron content, which may be the forerunner for
      subsequent clinical cardiac dysfunction.

PMID- 25370545
TI  - Purpose in life and its association with stress among persons living in a semi
      urban area of Tamil Nadu.
AB  - BACKGROUND: Purpose in life (PIL) is defined as the question concerning the
      significance or importance of life or one's existence. PIL is closely associated
      with spirituality and, hence, is an important determinant of health. This, in
      turn, leads to lower stress response and good mental health. OBJECTIVES: To
      assess the PIL and perceived psychosocial stress and to develop a conceptual
      understanding of the relation between the two. MATERIALS AND METHODS: A
      questionnaire was developed to understand the PIL in the cultural context of semi
      urban Tamil Nadu. Its internal consistency was checked and it was administered to
      227 conveniently selected individuals between 15 and 70 years of age. RESULTS:
      The questionnaire on PIL developed for this study had an acceptable internal
      consistency with a Cronbach's alpha of 0.883. Some common purposes in life
      mentioned by the people were recognition and acknowledgment for their roles and
      responsibilities, to be a part of a society that is higher class than their
      current frame, acceptance by people in society, to show people who disagree with
      them that they are wrong, to be treated with respect, to be known as a person
      with integrity, love for others, to be beneficial to others at the cost of
      themselves, to bring equity in the society, and to help others. It was also found
      that adherence to social norms as a PIL was associated with lower perceived
      stress. CONCLUSION: This study provides a conceptual understanding on the
      purposes in people's lives in the context of semi-urban Tamil Nadu and their
      association with perceived psychosocial stress.

PMID- 25370546
TI  - Involvement of the family members in caring of patients an acute care setting.
AB  - BACKGROUND: Family members are critical partners in the plan of care for patients
      both in the hospital and at home. Involving the members of the family in acute
      care can help the nursing staff in emergency. The present study was aimed to find
      out the role of the family members while caring for the patients admitted in
      emergency unit of a tertiary care hospital. MATERIALS AND METHODS: A total of 400
      family members of the patients were conveniently selected. Only one member per
      family was interviewed and their role in taking care of the patient in acute care
      setting was evaluated. RESULTS: The mean age of patients admitted in acute care
      setting was 46.6 yrs +/- 18.8 with the age range of 18-84 years. Majority (39%)
      of the patients were in the age group of 31-60 years. More than half of the
      caregivers of patients were males and 88% of them were first-degree relatives.
      The major tasks performed by the caregivers during the patient care was
      communicating with doctors/ nursing staff (98%), cleaning and dressing the
      patient (94%), feeding the patient (90%), procuring medication and other supplies
      (88%), administering oral medications (74%), changing position and helping for
      back care (65%), shifting the patients for investigations (60%), collecting
      reports (35%) and providing physiotherapy (25%). CONCLUSIONS: The results of the
      study concluded that family involvement in acute care setting can help the
      nursing staff in taking care of the patient in acute care setting and it also
      provides the opportunity for preparing them for after care of the patients at
      home following discharge.

PMID- 25370547
TI  - Prevalence and genotypic relatedness of methicillin resistant Staphylococcus
      aureus in a tertiary care hospital.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the most common
      multidrug-resistant pathogen causing nosocomial infections across the world. MRSA
      is not only associated with significant mortality and morbidity but also places a
      large economic strain on our health care system. MRSA isolates are also typically
      resistant to multiple, non-beta-lactam antibiotics. We conducted a prospective
      study in a tertiary care hospital, to determine the prevalence of MRSA and to
      establish the clonal distribution of MRSA isolates recovered from various
      clinical specimens. MATERIALS AND METHODS: Clinical samples were cultured and S.
      aureus was identified as per standard microbiological procedures. Susceptibility
      testing was done by agar disk diffusion and minimum inhibitory concentration
      (MIC) method as recommended by CLSI. Methicillin resistance was detected by
      phenotypic methods namely, oxacillin disc diffusion (ODD), minimum inhibitory
      concentration (MIC) of oxacillin, cefoxitin disk diffusion (CDD), and MIC of
      cefoxitin. Amplification of mecA gene by PCR was used as gold standard for
      detection of methicillin resistance. Pulsed field gel electrophoresis (PFGE)
      typing was performed for MRSA isolates. RESULTS: Out of 390 S. aureus isolates,
      154 (39.48%) isolates were MRSA and 236 (60.51%) isolates were MSSA. Penicillin
      was the least effective antibacterial drug against the hospital associated S.
      aureus isolates with 85.64% resistance rate. All the isolates were susceptible to
      vancomycin. The MRSA showed a high level of resistance to all antimicrobials in
      general in comparison to the MSSA and the difference was statistically
      significant (P < 0.05). Multiplex PCR performed for all strains showed
      amplification of both the mecA and nucA genes in MRSA strains whereas MSSA
      strains showed amplification of only nucA gene. PFGE of these isolates showed 10
      different patterns. CONCLUSION: Prevalence of MRSA in our hospital was 39.48%.
      Most of these isolates were resistant to erythromycin, clindamycin,
      cotrimoxazole, and ciprofloxacin, whereas high sensitivity was seen to vancomycin
      followed by gentamicin. CDD and MIC for cefoxitin showed 100% sensitivity,
      specificity, PPV and NPV as compared to PCR for mecA gene. In maximum number of
      isolates PFGE type A pattern was seen suggesting clonal relatedness.

PMID- 25370548
TI  - Unilateral superior vena cava syndrome.
AB  - An elderly man presented with clinical features of superior vena cava (SVC)
      syndrome restricted to the right side. Detailed evaluation suggested the
      diagnosis of unilateral SVC syndrome due to adenocarcinoma (presumably) from
      lung. With this case, we discuss the clinical presentation and causes of this
      rare clinical entity. Also, unilateral signs of SVC syndrome warrant a thorough
      clinical evaluation as it can be a presenting feature of a spectrum of diseases
      ranging from benign to malignant etiologies.

PMID- 25370549
TI  - Cerebellar superficial siderosis of chronic subarachnoid hemorrhage in a patient
      with Tacrolimus-associated posterior reversible encephalopathy.

PMID- 25370550
TI  - Aortic coarctation associated with an absent segment of the proximal right
      subclavian artery.
AB  - Coarctation of the aorta is a congenital anomaly of the thoracic aorta with many
      known associations. We describe the case of a young man referred for management
      of subarachnoid hemorrhage, in whom subsequent work-up revealed the previously
      undescribed combination of severe postductal aortic coarctation and an absent
      segment of the proximal right subclavian artery. 

PMID- 25370551
TI  - Recurrent malignant proliferating trichilemmal tumor with lymph node metastasis
      in a young woman.
AB  - Malignant proliferating trichilemmal tumor (MPTT) is a rare cutaneous tumor
      predominantly affecting the scalp, eyelids, neck and face of elderly women. It is
      a large, solitary, multilobulated lesion that may arise within a pilar cyst.
      These tumors are largely benign, often cystic, and are characterized by
      trichilemmal keratinization. However, at times, the tumor has an aggressive
      clinical course and a propensity for nodal and distant metastases. Wide local
      excision with a 1 cm margin of normal tissue is the treatment of choice. Adjuvant
      chemotherapy and radiotherapy have been occasionally used to prevent recurrence
      in MPTT. This is a case report of a recurrent malignant trichilemmal tumor over
      scalp in a young female patient with nodal metastasis.

PMID- 25370552
TI  - Tumor to tumor metastasis: adenocarcinoma of lung metastatic to meningioma.
AB  - Tumor-to-tumor metastasis (T2Tmets) is an established entity but often overlooked
      and underdiagnosed. Merely 84 such cases are reported in literature till date.
      The authors here describe a 65-year-old man presenting with first episode of
      focal seizure and incidentally turned out to be a case of adenocarcinoma of lung
      metastatic to a meningioma. The diagnosis of T2Tmets was based solely on
      histopathological criteria. Recent advent of brain imaging revolutionized its
      diagnosis and it has moved from the realm of thologists to that of radiologists.
      In our case, diagnosis was also established by immunohistochemistry.

PMID- 25370553
TI  - Resolution of granuloma annulare following treatment with bendamustine and
      rituximab in a patient with follicular lymphoma: a serendipitous finding.
AB  - Granuloma annulare is a benign inflammatory dermatosis. Cell-mediated immunity
      and delayed hypersensitivity are proposed pathogenic mechanisms. We report in
      this paper a case of generalized granuloma annulare that resolved after the
      patient was treated with rituximab and bendamustine for stage IV follicular
      lymphoma.

PMID- 25370554
TI  - Longitudinal extensive transverse myelitis due to tuberculosis: a report of four
      cases.
AB  - Tuberculosis of the central nervous system (CNS) accounts for approximately 1% of
      all cases of tuberculosis and half of these involve the spine. Intramedullary
      involvement is rare in tuberculosis and usually present in the form of
      radiculomyelitis, transverse myelitis, intraspinal granulomas, or thrombosis of
      anterior spinal artery. Transverse myelitis typically extends two or less spinal
      segments, whereas longitudinal extensive transverse myelitis (LETM) extends three
      or more spinal segments in length and may occasionally span all the segments of
      the spinal cord. LETM is most frequently associated with neuromyelitis optica
      (NMO). Moreover, associations between NMO and active pulmonary tuberculosis have
      been suggested by a number of case reports and case series. We present here four
      cases of spinal tuberculosis that presented with LETM and none of them had a
      clinical profile fulfilling the diagnostic criteria for NMO.

PMID- 25370555
TI  - Prenatal diagnosis of partial trisomy 21 associated with maternal balanced
      translocation 46,XX, der(21)t(21;22) with pericentric inversion of chromosome 9.

PMID- 25370556
TI  - Comment on ''gastrointestinal bleeding under dabigatran''.

PMID- 25370557
TI  - Ratio of controls to cases: a design decision.

PMID- 25370558
TI  - Serum high density lipoprotein cholesterol and Duke Treadmill score.

PMID- 25370559
TI  - Social desirability bias in face to face interviews.

PMID- 25370560
TI  - Surgical site infections in orthopedic trauma surgeries.

PMID- 25370561
TI  - Duke's treadmill score in diabetics-does it really matter?

PMID- 25370562
TI  - Dengue infection and acute hypokalemic quadriparesis.

PMID- 25370563
TI  - Dengue-related hypokalemic paralysis-more questions than answers.

PMID- 25370564
TI  - Quadriparesis and hypokalemia in dengue.

PMID- 25370565
TI  - Lymphocytic hypophysitis in non-pregnant middle-aged females mimicking pituitary
      adenoma: a report of two cases.

PMID- 25370566
TI  - Hand-grenade splinter-induced hypopituitarism.

PMID- 25370567
TI  - Facial cutaneous metastases of advanced rectal malignancy masquerading as lip
      cancer.

PMID- 25370569
TI  - Perceived control and self-efficacy, subjective well-being and lifestyle
      behaviours in young Iranian women.
AB  - This study examined whether young Iranian women's perceived control and self
      efficacy, as a component of cognitive social capital, predicts health and well
      being. A total of 391 women aged between 18 and 35 years completed a survey
      including scales measuring control and self-efficacy and health outcomes
      including quality of life, satisfaction with life and lifestyle behaviours.
      Statistical analyses indicated that participants had low perceived control and
      influence over community affairs together with high perceived control over their
      personal lives. Multiple regression analyses indicated the predictive role of
      control and self-efficacy for well-being outcomes suggesting the potential role
      for health interventions targeting control and self-efficacy.

PMID- 25370568
TI  - The role of death receptor 3 in the biological behavior of hepatocellular
      carcinoma cells.
AB  - Death receptor 3 (DR3) belongs to the tumor necrosis factor (TNF) receptor
      superfamily, primarily found in lymphoid tissues. Reports have determined that
      DR3 may also be distributed in numerous types of tumors. Therefore, it is thought
      that DR3 may have an important role in the process of tumorigenesis. The aim of
      the present study was to observe the effect of silencing DR3 expression on
      hepatocarcinoma cell growth, apoptosis and invasion in order to elucidate the
      role of DR3 in tumor development. The hepatocarcinoma cell lines (HepG2, Huh7,
      SMMC7721 and Bel-7402) and normal human liver cells (HL-7702) were transfected
      with three stealth RNA interference (RNAi) sequences that target the DR3 gene.
      Reverse transcription quantitative polymerase chain reaction was used to detect
      the expression levels of DR3 in hepatocarcinoma cell lines and normal liver HL
      7702 cells. MTT assay and flow cytometry (FCM) were used to determine the rates
      of cell proliferation and apoptosis, respectively. Following silencing of the DR3
      gene, western blot analysis was used to determine the protein expression of P53,
      Fas, Caspase8, nuclear factor kappa-light-chain-enhancer of activated B cells (NF
      kappaB) and Caspase3. DR3 messenger RNA (mRNA) expression in hepatocarcinoma cell
      lines was significantly increased compared with that in the normal liver cell
      line. Three targeted DR3 gene small interfering RNAs significantly inhibited DR3
      gene expression in Bel-7402 cells at the nucleic acid level.
      AF02670.1_stealth_883 and cocktail demonstrated the most efficient inhibition of
      DR3 gene expression at 48 and 72 h following transfection, with mRNA inhibition
      rates of 89.46 and 92.75%, and 90.53 and 94.25% (P<0.01), respectively. Cell
      viability was significantly reduced by AF02670.1_stealth_883 and RNAi cocktail at
      24, 48 and 72 h following transfection. The inhibition rates of cell
      proliferation were 50.76 and 61.76% (P<0.05) at 72 h following transfection. FCM
      revealed that AF02670.1_stealth_883 and RNAi cocktail also induced apoptosis in
      Bel-7402 cells at 72 h following transfection. Reduction of NF-kappaB and P53
      levels was observed (P<0.05) in Bel-7402 cells following DR3 silencing, whereas
      levels of Fas, Caspase3 and Caspase8 were markedly elevated (P<0.05). DR3
      expression levels in hepatocellular carcinoma cells were significantly higher
      than those in normal cells. DR3 silencing effectively inhibited proliferation and
      invasion of hepatocellular carcinoma cells in vitro. However, silencing of the
      DR3 gene affect levels of apoptosis antigen-3 ligand in cells, therefore
      indicating that it may be involved with other pathways that regulate apoptosis in
      HCCs. In conclusion, the results of the present study indicated that DR3 may be a
      promising therapeutic target molecule for further study of hepatocellular
      carcinoma gene therapy.

PMID- 25370570
TI  - The relationship between nature relatedness and anxiety.
AB  - This study investigated the relationship between anxiety and feelings of being
      connected to nature. Two standardised self-report scales, the Nature Relatedness
      Scale and the State Trait Inventory for Cognitive and Somatic Anxiety, were used
      in tandem with a qualitative question. Quantitative results indicated that
      connection to nature was significantly related to lower levels of overall, state
      cognitive and trait cognitive anxiety. Qualitative results revealed seven themes:
      relaxation, time out, enjoyment, connection, expanse, sensory engagement and a
      healthy perspective. Taken together, these results suggest that opportunities
      that enhance experiences of being connected to nature may reduce unhelpful
      anxiety.

PMID- 25370571
TI  - Effect of a short-term psychological intervention on the anxiety and depression
      of amyotrophic lateral sclerosis patients.
AB  - This study evaluated the effectiveness of a psychological intervention in
      amyotrophic lateral sclerosis patients, consisting of four semi-structured
      sessions of cognitive behavioural therapy combined with counselling techniques.
      An intervention group and a control group were established. The Hospital Anxiety
      and Depression Scale was used to assess levels of anxiety and depression. In
      total, fifty-four patients took part. Prior to the intervention, the intervention
      group displayed rates of 63.3 and 36.7 per cent for anxiety and depression,
      respectively, falling to 16.7 and 10.0 per cent afterwards. The psychological
      intervention demonstrated potential for the reduction of levels of anxiety and
      depression in amyotrophic lateral sclerosis patients.

PMID- 25370572
TI  - Social ecological factors associated with future orientation of children affected
      by parental HIV infection and AIDS.
AB  - From a social ecological perspective, this study examined the effects of stigma
      (societal level), trusting relationships with current caregivers (familial
      level), and self-esteem (individual level) on future orientation of children
      affected by HIV infection and AIDS. Comparing self-report data from 1221 children
      affected by parental HIV infection and AIDS and 404 unaffected children, affected
      children reported greater stigma and lower future orientation, trusting
      relationships, and self-esteem. Based on structural equation modeling, stigma
      experiences, trusting relationships, and self-esteem had direct effects on future
      orientation, with self-esteem and trusting relationships partially mediating the
      effect of stigma experiences on children's future orientation. Implications are
      discussed.

PMID- 25370573
TI  - Loss of function of SWI/SNF chromatin remodeling genes leads to genome
      instability of human lung cancer.
AB  - SWI/SNF chromatin remodeling complexes are frequently mutated in a variety of
      human cancers. We investigated the mutation incidence and the role of mSWI/SNF
      (BAF) complexes in human lung cancer. In the present study, we analyzed somatic
      mutations of BAF complexes and other driver mutated genes of lung carcinoma
      deposited in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. BAF
      complexes were mutated in 282 of 803 (35.12%) lung carcinoma samples analyzed,
      ranking second to TP53. Significantly, BAF-mutated samples exhibited more genomic
      mutations than BAF wild-type ones. Moreover, a significant positive correlation
      existed between the BAF mutations and overall genomic mutations in these lung
      carcinoma samples (P<0.001, Pearson's correlation analysis). Specifically, the
      mutant-typing of 6 BAF genes, SMARCA4, ARID2, ARID1B, BCL11A, BCL11B and BRD9 was
      associated with more overall mutations in the lung carcinoma samples. A mutation
      reporter system was developed by means of the establishment of stable cell
      sublines with slippage-luciferase transcript in a lung adenocarcinoma cell line,
      Calu-3. SMARCA4, the most frequently mutated BAF gene in lung cancer, was stably
      knocked down by pSUPER constructs carrying short hairpin RNA (shRNA). Mutation
      ratios determined from the mutation reporters of Calu-3 cells were significantly
      increased upon stable SMARCA4 knockdown. We demonstrated that genetic mutations
      of BAF complexes lead to genome instability of lung carcinoma. Therefore, BAF
      complexes play an important role in maintaining genome stability in human lung
      cancer.

PMID- 25370574
TI  - Interaction of epoxyeicosatrienoic acids and adipocyte fatty acid-binding protein
      in the modulation of cardiomyocyte contractility.
AB  - BACKGROUND: Adipocyte fatty acid-binding protein (FABP4) is a member of a highly
      conserved family of cytosolic proteins that bind with high affinity to
      hydrophobic ligands, such as saturated and unsaturated long-chain fatty acids and
      eicosanoids. Recent evidence has supported a novel role for FABP4 in linking
      obesity with metabolic and cardiovascular disorders. In this context, we
      identified FABP4 as a main bioactive factor released from human adipose tissue
      that directly suppresses heart contraction in vitro. As FABP4 is known to be a
      transport protein, it cannot be excluded that lipid ligands are involved in the
      cardiodepressant effect as well, acting in an additional and/or synergistic way.
      OBJECTIVE: We investigated a possible involvement of lipid ligands in the
      negative inotropic effect of adipocyte factors in vitro. RESULTS: We verified
      that blocking the CYP epoxygenase pathway in adipocytes attenuates the inhibitory
      effect of adipocyte-conditioned medium (AM) on isolated adult rat cardiomyocytes,
      thus suggesting the participation of epoxyeicosatrienoic acids (EETs) in the
      cardiodepressant activity. Analysis of AM for EETs revealed the presence of 5,6-,
      8,9-, 11,12- and 14,15-EET, whereas 5,6-EET represented about 45% of the total
      EET concentration in AM. Incubation of isolated cardiomyocytes with EETs in
      similar concentrations as found in AM showed that 5,6-EET directly suppresses
      cardiomyocyte contractility. Furthermore, after addition of 5,6-EET to FABP4, the
      negative inotropic effect of FABP4 was strongly potentiated in a concentration
      dependent manner. CONCLUSIONS: These data suggest that adipocytes release 5,6-EET
      and FABP4 into the extracellular medium and that the interaction of these factors
      modulates cardiac function. Therefore elevated levels of FABP4 and 5,6-EET in
      obese patients may contribute to the development of heart dysfunction in these
      subjects.

PMID- 25370575
TI  - Body size estimation and other psychosocial risk factors for obesity onset among
      US adolescents: findings from a longitudinal population level study.
AB  - BACKGROUND/OBJECTIVE: The purpose of this study was to examine the longitudinal
      effects of body size over- and underestimation and other psychosocial factors on
      the risk for onset of overweight (OW) or obesity (OB) 1 year later among US
      adolescents. SUBJECTS/METHODS: Participants with non-missing height and weight
      were drawn from the first two waves of the National Longitudinal Study of
      Adolescent to Adult Health (n=13,568). Multinomial logistic regressions were
      conducted to assess longitudinal risk factors for OW and OB onset, controlling
      for baseline weight status, age, race/ethnicity, parent education and family
      structure. Analyses were stratified by sex. RESULTS: Compared with accurate body
      size perception, body size overestimation increased the relative risk (RR) of OW
      onset among women and men (RR=3.34, confidence interval (CI)=2.39-4.68; RR=6.01,
      CI=4.09-8.83, respectively, P<0.001) in fully adjusted models including body mass
      index z-scores. Body size underestimation decreased the RR of OW onset among
      women and men (RR= 0.08, CI=0.03-0.20; RR=0.13, CI=0.06-0.27, respectively) and
      OB onset (RR=0.05, CI=0.02-0.14; RR=0.19, CI=0.08-0.47, respectively, P<0.001 for
      all) in fully adjusted models. Dieting, extreme weight loss behaviors and
      skipping breakfast at Wave 1 increased the risk of OB onset by Wave 2.
      CONCLUSIONS: Contrary to a common assumption, body size underestimation did not
      increase, but in fact decreased, the RR for the onset of OW and of OB among
      adolescents using a prospective longitudinal design. However, body size
      overestimation predicted onset of OW 1 year later. Body size self-concept and
      other psychosocial factors have an important role in risk for OW and for OB among
      both males and females during adolescence.

PMID- 25370576
TI  - IGFBP-2 inhibits adipogenesis and lipogenesis in human visceral, but not
      subcutaneous, adipocytes.
AB  - BACKGROUND/OBJECTIVE: IGF-binding protein (IGFBP)-2 is the principal IGFBP
      produced by white adipocytes during adipogenesis, and circulating levels are
      reduced in obesity. Overexpression of IGFBP-2 in transgenic mice prevents
      obesity, but depot-specific effects of IGFBP-2 on adipo/lipogenesis are unknown.
      The present study aimed to investigate whether IGFBP-2 affects adipo/lipogenesis
      in a depot-specific manner and explore potential mechanisms. METHODS: Following
      adipocyte characterisation, IGFBP-2 levels were measured from human subcutaneous
      and visceral preadipocytes, and IGFBP-2 dose-responses were then undertaken with
      exogenous IGFBP-2 in an in vitro IGF-I-free system to examine adipo/lipogenesis.
      Following this, both types of adipocytes were transfected with human siRNA IGFBP
      2 to assess auto-/para-/intra-crine effects, with and without additional add-back
      IGFBP-2. To elucidate the potential mechanisms, visceral preadipocytes were
      treated with either wild-type or Heparin Binding Domain (HBD)-mutant IGFBP-2
      (which is unable to bind to cell-surface components), and experiments were also
      undertaken using Echistatin (an integrin receptor blocker). Outcomes included
      gene expression profiles, protein levels and phosphorylation and lipid staining.
      RESULTS: Human visceral adipocytes produced significantly more IGFBP-2 than
      subcutaneous adipocytes. Subsequent dose-responses to IGFBP-2 demonstrated
      significant reductions in adipo/lipogenesis in visceral, but not subcutaneous,
      adipocytes in response to increasing IGFBP-2. Silencing IGFBP-2 resulted in
      exaggerated adipo/lipogenesis in visceral, but not subcutaneous, adipocytes, an
      effect completely inhibited by add-back IGFBP-2. These effects occurred in the
      absence of changes in IGF-I levels. HBD-mutant IGFBP-2 had reduced effects
      compared with wild-type IGFBP-2. Wild-type IGFBP-2 increased phosphorylation of
      focal adhesion kinase (FAK) and decreased phosphatase and tensin homolog (PTEN)
      levels, suggestive of integrin-mediated signalling. Blockade of this signalling,
      using Echistatin, completely negated the effects of IGFBP-2 on visceral
      adipo/lipogenesis. CONCLUSION: IGFBP-2 inhibits both adipogenesis and lipogenesis
      in visceral, but not subcutaneous, adipocytes. This depot-specific impairment
      appears to be independent of IGF-I and involves cell-surface association of IGFBP
      2 and activation of integrin signalling pathways.

PMID- 25370577
TI  - Lipomatosis of the mons pubis secondary to localized scleroderma (Morphea): first
      report of surgical management.

PMID- 25370578
TI  - Sepsis-related deaths in Brazil: an analysis of the national mortality registry
      from 2002 to 2010.
AB  - INTRODUCTION: Limited population-based epidemiologic information about sepsis'
      demography, including its mortality and temporal changes is available from
      developing countries. We investigated the epidemiology of sepsis deaths in Brazil
      using secondary data from the Brazilian Mortality Information System. METHODS:
      Retrospective descriptive analysis of Brazilian multiple-cause-of-death data
      between 2002 and 2010, with sepsis-associated International Classification of
      Diseases, 10th Revision (ICD-10) code indicated as the cause of death. Population
      based sepsis associated mortality rates and trends were estimated. Annual
      population-based mortality rates were calculated using age-stratified population
      estimates from the 2010 census provided by the Brazilian Institute of Geography
      and Statistics as denominators. RESULTS: The total number of annual deaths
      recorded in Brazil increased over the decade, from 982,294 deaths reported in
      2002 to 1,133,761 deaths reported in 2010. The number of sepsis associated deaths
      also increased both in absolute numbers and proportions from 95,972 (9.77% of
      total deaths) in 2002 to 186,712 deaths (16.46%) in 2010. The age-adjusted rate
      of sepsis-associated mortality increased from 69.5 deaths per 100,000 to 97.8
      deaths per 100,000 population from 2002 to 2010 (P < 0.001). Sepsis-associated
      mortality was higher in individuals older than 60 years of age as compared to
      subjects aged 0 to 20 years (adjusted rate ratio 15.7 (95% confidence interval
      (CI) 15.6 to 15.8)) and in male subjects (1.15 (95% CI 1.15 to 1.16)).
      CONCLUSIONS: Between 2002 and 2010 the contribution of sepsis to all cause
      mortality as reported in multiple-cause-of-death forms increased significantly in
      Brazil. Age-adjusted mortality rates by sepsis also increased in the last decade.
      Our results confirm the importance of sepsis as a significant healthcare issue in
      Brazil.

PMID- 25370579
TI  - Epigallocatechin-3-gallate induces the apoptosis of hepatocellular carcinoma LM6
      cells but not non-cancerous liver cells.
AB  - Epigallocatechin-3-gallate (EGCG) is a constituent of green tea and has been
      associated with anticancer activity. In the present study, the inhibitory effect
      of EGCG on human hepatocellular cancer cells was examined by cell viability
      assay, in vitro apoptosis assay and cell cycle analysis. In addition, gene
      expression was measured to elucidate the molecular mechanisms of action of EGCG
      by mitochondrial membrane potential (MMP) determination and western blot
      analysis. We demonstrated that EGCG induced apoptosis, decreased mitochondrial
      membrane potential and promoted G0/G1 phase cell cycle arrest of HCCLM6 cells but
      not that of non-cancerous liver cells (HL-7702). The EGCG-induced apoptosis of
      HCCLM6 cells was associated with a significant decrease in Bcl-2 and NF-kappaB
      expression. In addition, the expression of Bax, p53, caspase-9 and caspase-3
      increased, and cytochrome c was released. These results suggest that EGCG
      inhibits the progression of cancer through cytocidal activity and that it is a
      potential therapeutic compound for hepatocellular carcinoma (HCC).

PMID- 25370580
TI  - Attitudes need to change for patients to be more involved in care, says think
      tank.

PMID- 25370581
TI  - 18FDG-PET-CT: an imaging biomarker of high-risk carotid plaques. Correlation to
      symptoms and microembolic signals.
AB  - BACKGROUND AND PURPOSE: We investigated whether uptake of (18)fluoro-2-deoxy-d
      glucose (18FDG) positron emission tomography-computed tomography (PET-CT)
      correlated to clinical symptoms and presence of microembolic signals (MES)
      detected by transcranial Doppler in patients with carotid stenosis. METHODS:
      18FDG-PET-CT and MES detection was performed in consecutive patients with 50% to
      99% symptomatic or asymptomatic carotid stenoses. Uptake index was defined by a
      target to background ratio (TBR) between maximum standardized uptake value of the
      carotid plaque and the mean standardized uptake value of the jugular veins. End
      points for analysis were presence of symptoms and presence of MES. RESULTS: We
      included 123 stenosis derived from 110 patients, 60 symptomatic and 63
      asymptomatic. MES positive (+) lesions were found in 16%. TBR values were higher
      in symptomatic compared with asymptomatic (median 2.07 versus 1.78; P<0.0018) and
      in MES+ compared with MES- plaques (median 2.14 versus 1.86; P<0.008). TBR values
      were also higher in asymptomatic MES+ compared with MES- plaques (median 1.97
      versus 1.76; P<0.03). The best TBR threshold value for symptomatic versus
      asymptomatic, for MES+ versus MES-, for symptomatic MES+ versus symptomatic or
      asymptomatic MES-, and for asymptomatic MES+ versus asymptomatic MES- plaques was
      1.9. Sensitivity/specificity were, respectively, 56/77%, 73/63%, 79/64%, and
      80/77%. We found a strong correlation between number of MES and TBR values (rho
      0.26; P=0.0043). CONCLUSIONS: 18FDG-PET-CT accurately detected high-risk carotid
      plaques. Also given its strong correlation to MES, 18FDG-PET-CT may be a useful
      tool in clinical practice.

PMID- 25370582
TI  - White matter edema at the early stage of cerebral autosomal-dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy.
AB  - BACKGROUND AND PURPOSE: Recently, in a mouse model of cerebral autosomal-dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy, a monogenic
      cerebral small vessel disease, intramyelinic edema was detected in the white
      matter (WM) early during the course of the disease. We hypothesized that if this
      mechanism holds true in patients, it would translate in larger WM volume. We
      aimed to measure WM volume in patients with cerebral autosomal-dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy in comparison with
      age- and sex-matched controls, along with the ratio of cortical surface area to
      the volume of brain hemispheres as an indirect measure that should be reduced in
      patients. METHODS: Twenty patients at the early stage of the disease (Mini Mental
      State Examination >24 and modified Rankin scale <=1) and 27 age- and sex-matched
      controls had high-quality 3-Tesla 3DT1 MRI acquisitions. Volumes of brain
      hemispheres and of WM were determined. The ratio of cortical surface area to the
      volume of brain hemispheres was evaluated as a proxy of underlying WM volume.
      RESULTS: Patients had larger volumes of WM than controls (patients: 479.4+/-71.7;
      controls: 463.9+/-44.2; P=0.03). They presented a lower cortical surface area and
      cortical volume leading to a lower ratio of cortical surface area to the volume
      of brain hemispheres (patients: 15.7+/-0.7; controls: 16.1+/-0.5; P=0.004).
      Volume of WM tended to be associated with that of WM hyperintensities (P=0.06).
      CONCLUSIONS: Patients with cerebral autosomal-dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy have larger WM volume than age- and
      sex-matched controls, a finding compatible with the hypothesis of intramyelinic
      edema as observed recently in mice.

PMID- 25370583
TI  - In vivo imaging of the mouse neurovascular unit under chronic cerebral
      hypoperfusion.
AB  - BACKGROUND AND PURPOSE: Proper brain function is maintained by an integrated
      system called the neurovascular unit (NVU) comprised cellular and acellular
      elements. Although the individual features of specific neurovascular components
      are understood, it is unknown how they respond to ischemic stress as a functional
      unit. Therefore, we established an in vivo imaging method and clarified the NVU
      response to chronic cerebral hypoperfusion. METHODS: Green mice (b-act-EGFP) with
      SR101 plasma labeling were used in this experiment. A closed cranial window was
      made over the left somatosensory cortex. To mimic chronic cerebral hypoperfusion,
      mice were subjected to bilateral common carotid artery stenosis operations using
      microcoils. In vivo real-time imaging was performed using 2-photon laser-scanning
      microscopy during the preoperative period, and after 1 day and 1 and 2 weeks of
      bilateral common carotid artery stenosis or sham operations. RESULTS: Our method
      allowed 3-dimensional observation of most of the components of the NVU, as well
      as dynamic capillary microcirculation. Under chronic cerebral hypoperfusion, we
      did not detect any structural changes of each cellular component in the NVU;
      however, impairment of microcirculation was detected over a prolonged period. In
      the pial small arteries and veins, rolling and adhesion of leukocyte were
      detected, more prominently in the latter. In the deep cortical capillaries, flow
      stagnation because of leukocyte plugging was frequently observed. CONCLUSIONS: We
      established an in vivo imaging method for real-time visualization of the NVU. It
      seems that under chronic cerebral hypoperfusion, leukocyte activation has a
      critical role in microcirculation disturbance.

PMID- 25370584
TI  - Quantitative measurement of physical activity in acute ischemic stroke and
      transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to quantitatively measure
      and describe the amount and pattern of physical activity in patients within the
      first week after acute ischemic stroke and transient ischemic attack using
      accelerometers. METHODS: A total of 100 patients with acute ischemic stroke or
      transient ischemic attack admitted to our acute stroke unit wore Actical
      accelerometers attached to both wrists and ankles and the hip for <=7 days.
      Patients were included within 72 hours of symptom onset. Accelerometer output was
      measured in activity counts (AC). Patients were tested daily with Scandinavian
      Stroke Scale. RESULTS: Physical activity peaked in the morning and declined
      during the rest of the day. In patients with stroke, total AC were 71% lower than
      in patients with transient ischemic attack. AC were 80% lower in the paretic
      compared with those in the nonparetic arm in patients with ischemic stroke. For
      the legs AC were 44% lower on the paretic side and an overall increase in AC with
      time was found. There was a significant increase in AC with increasing
      Scandinavian Stroke Scale and a decrease in AC with increasing age. CONCLUSIONS:
      This study demonstrates the feasibility of using accelerometers to quantitatively
      and continuously measure physical activity simultaneously from all 4 extremities
      and the hip in patients with acute ischemic stroke and transient ischemic attack.
      Our study provides quantitative evidence of physical inactivity in patients with
      acute ischemic stroke. The method offers a low cost and noninvasive tool for
      future clinical interventional physiotherapeutic and early mobilization studies.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01560520.

PMID- 25370585
TI  - Frequency and predictors of stroke after acute myocardial infarction: specific
      aspects of in-hospital and postdischarge events.
AB  - BACKGROUND AND PURPOSE: Stroke is a serious complication after acute myocardial
      infarction (AMI) and is closely associated with decreased survival. This study
      aimed to investigate the frequency, characteristics, and factors associated with
      in-hospital and postdischarge stroke in patients with AMI. METHODS: Eight
      thousand four hundred eighty-five consecutive patients admitted to a cardiology
      intensive care unit for AMI, between January 2001 and July 2010. Stroke/transient
      ischemic attack were collected during 1-year follow-up. RESULTS: One hundred
      twenty-three in-hospital strokes were recorded: 65 (52.8%) occurred on the first
      day after admission for AMI, and 108 (87%) within the first 5 days. One hundred
      six patients (86.2%-incidence rate 1.25%) experienced in-hospital ischemic
      stroke, and 14 patients (11.4%-incidence rate 0.16%) were diagnosed with an in
      hospital hemorrhagic stroke. In-hospital ischemic stroke subtypes according to
      the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification showed
      that only 2 types of stroke were identified more frequently. As expected, the
      leading subtype of in-hospital ischemic stroke was cardioembolic stroke (n=64,
      60%), the second was stroke of undetermined pathogenesis (n=38, 36%). After
      multivariable backward regression analysis, female sex, previous transient
      ischemic attack (TIA)/stroke, new-onset atrial fibrillation, left ventricular
      ejection fraction (odds ratio per point of left ventricular ejection fraction),
      and C-reactive protein were independently associated with in-hospital ischemic
      stroke. When antiplatelet and anticoagulation therapy within the first 48 hours
      was introduced into the multivariable model, we found that implementing these
      treatments (>=1) was an independent protective factor of in-hospital stroke. In
      hospital hemorrhagic stroke was dramatically increased (5-fold) when thrombolysis
      was prescribed as the reperfusion treatment. However, the different parenteral
      anticoagulants were not predictors of risk in univariable analysis. Finally, only
      45 postdischarge strokes were recorded. Postdischarge stroke subtypes showed a
      more heterogeneous distribution of mechanisms. The annual rate of stroke post-AMI
      remained stable throughout the 10-year study period. CONCLUSIONS: The present
      study describes specific predictors of in-hospital and postdischarge stroke in
      patients with AMI. It showed a marked increase in the risk of death, both during
      hospitalization and in the year after AMI. After hospital discharge, stroke
      remains a rare event and is mostly associated with high cardiovascular risk.

PMID- 25370586
TI  - Intraluminal cell transplantation prevents growth and rupture in a model of
      rupture-prone saccular aneurysms.
AB  - BACKGROUND AND PURPOSE: Aneurysm occlusion by intraluminal thrombus formation is
      the desired effect of all endovascular treatments. Intraluminal thrombus may,
      however, recanalize and be absorbed, unless it is infiltrated by cells that turn
      it into fibrous tissue (neointima). Because ruptured aneurysm walls are
      characterized by loss of smooth muscle cells, we assessed the impact of mural
      cell loss on wall remodeling of thrombosed aneurysms and investigated whether
      neointima formation could be enhanced by direct transplantation of cells into the
      thrombus. METHODS: Sidewall aneurysms were microsurgically created in rats
      (n=81). Certain aneurysms were decellularized. Thrombosis was induced using
      direct injection of a fibrin polymer into the aneurysm. CM-Dil-labeled smooth
      muscle cells were injected into 25 of 46 fibrin embolized aneurysms.
      Recanalization and aneurysm growth were monitored with magnetic resonance
      angiography. Endoscopy, optical projection tomography, histology, and
      immunohistochemistry were used to study the fate of transplanted cells, thrombus
      organization, and neointima formation. RESULTS: Decellularized embolized
      aneurysms demonstrated higher angiographic recurrence compared with
      decellularized embolized aneurysms with transplanted cells (P=0.037). Local cell
      replacement at the time of thrombosis resulted in better histological neointima
      formation than both nondecellularized embolized aneurysms (P<0.001) and
      decellularized embolized aneurysms (P=0.002). Aneurysm growth and rupture were
      observed exclusively in decellularized embolized aneurysms. CONCLUSIONS: Lack of
      smooth muscle cells in the aneurysm wall promotes wall degradation, aneurysm
      growth and rupture, even if the aneurysm is occluded by luminal thrombus.
      Transplantation of smooth muscle cells into the luminal thrombus can reduce this
      degenerative remodeling.

PMID- 25370588
TI  - Physical activity and exercise after stroke: review of multiple meaningful
      benefits.

PMID- 25370587
TI  - Effect of alteplase within 6 hours of acute ischemic stroke on all-cause
      mortality (third International Stroke Trial).
AB  - BACKGROUND AND PURPOSE: Prompt thrombolytic therapy with intravenous alteplase
      reduces disability after acute ischemic stroke. In an exploratory analysis, we
      examined whether long-term survival varied by baseline characteristics after
      alteplase. METHODS: In this open-treatment, international, randomized, controlled
      trial, ischemic stroke patients were randomly allocated <6 hours of onset to
      intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care
      alone (n=1520). We followed patients to death, censoring when last known to be
      alive. We grouped patients by delay to randomization, and good or poor predicted
      prognosis (calculated from baseline National Institutes of Health Stroke Scale
      [NIHSS] score and age). We present absolute mortality differences between treated
      and control groups at 7 days, 6 months, and 18 months poststroke. RESULTS:
      Alteplase was not associated with a significant increase in mortality within 18
      months (0.6% [95% confidence interval (CI), -2.9% to +4.2] P=0.72] in all
      patients with complete vital status (99.9%, 3034/3035). In patients randomized <3
      hours of stroke, 18-month mortality was lower in the alteplase-treated group than
      the control group (40.6% [95% CI, 42.6-52.7] versus 47.8% [95% CI, 35.5-45.3];
      P=0.0434]. The difference in 18-month mortality between alteplase-treated and
      control patients was greater in patients who were randomized early (<3 hours)
      compared with late (3-6 hours; +9% [95% CI, 1-17]; P=0.0317). Alteplase led to a
      greater improvement in 18-month survival in patients with a poor prognosis than
      in patients with a good prognosis (+8% [95% CI, 2-14]; P=0.0091). CONCLUSIONS:
      These exploratory analyses of the third International Stroke Trial (IST-3) trial
      support improving acute stroke patients' access to earlier alteplase treatment,
      treatment of patients with poor prognosis, and further randomized controlled
      trials in minor stroke to replicate these findings. CLINICAL TRIAL REGISTRATION
      URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25765518.

PMID- 25370590
TI  - Incremental predictive value of carotid inflammation in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Microwave Radiometry (MWR) allows in vivo noninvasive
      assessment of internal temperature of tissues. The aim of the present study was
      to evaluate in patients with ischemic stroke and bilateral carotid plaques (1)
      whether ipsilateral carotid arteries exhibit higher temperature differences
      (DeltaT), as assessed by MWR; (2) the predictive accuracy of MWR in symptomatic
      carotid artery identification. METHODS: Consecutive patients with recent acute
      anterior circulation ischemic stroke because of large artery atherosclerosis were
      included in the study. Carotid arteries of all patients were evaluated by carotid
      ultrasound and MWR. RESULTS: In total, 50 patients were included in the study.
      Culprit carotid arteries had higher DeltaT compared with nonculprit (0.93+/-0.58
      versus 0.58+/-0.35 degrees C; P<0.001). The addition of DeltaT to a risk
      prediction model based only on ultrasound plaque characteristics increased its
      predictive accuracy significantly (c-statistic: 0.691 versus 0.768; Pdif=0.05).
      CONCLUSIONS: Culprit carotid arteries show higher thermal heterogeneity compared
      with nonculprit carotid arteries in patients with acute ischemic stroke and
      bilateral carotid plaques. MWR has incremental value in culprit carotid artery
      discrimination.

PMID- 25370591
TI  - Injury prevention in male veteran football players - a randomised controlled
      trial using "FIFA 11+".
AB  - The warm-up programme "FIFA 11+" has been shown to reduce football injuries in
      different populations, but so far veteran players have not been investigated. Due
      to differences in age, skill level and gender, a simple transfer of these results
      to veteran football is not recommended. The purpose of this study was to
      investigate the preventive effects of the "FIFA 11+" in veteran football players.
      Twenty veteran football teams were recruited for a prospective 9-month (1 season)
      cluster-randomised trial. The intervention group (INT, n = 146; 45 +/- 8 years)
      performed the "FIFA 11+" at the beginning of each training session, while the
      control group (CON, n = 119; 43 +/- 6 years) followed its regular training
      routine. Player exposure hours and injuries were recorded according to an
      international consensus statement. No significant difference was found between
      INT and CON in overall injury incidence (incidence rate ratio [IRR]: 0.91 [0.64
      1.48]; P = 0.89). Only severe injuries reached statistical significance with
      higher incidence in CON (IRR: 0.46 [0.21-0.97], P = 0.04). Regular conduction
      (i.e. once a week) of the "FIFA 11+" did not prevent injuries in veteran
      footballers under real training and competition circumstances. The lack of
      preventive effects is likely due to the too low overall frequency of training
      sessions.

PMID- 25370592
TI  - Non-pharmacological management of problematic sleeping in children with
      developmental disabilities.
AB  - AIM: Sleep is important for underlying neural plasticity, and children with
      developmental disabilities suffer behavioural, emotional, cognitive, and sensory
      motor issues that affect their wake and sleep states. Problematic sleeping can be
      hypothesized to have adverse effects on both of these areas in children with
      developmental disabilities. With this review, we aim to provide a benchmark in
      managing problematic sleeping in children with developmental disabilities.
      METHOD: A literature search was conducted and data on the study descriptives,
      patient characteristics, study design, study-related factors, criteria applied to
      operationalize sleep and developmental disability, and sleep 'management' were
      collected. Each management strategy was tabulated and analysed. RESULTS: We
      identified 90 studies involving 1460 children with developmental disabilities, of
      whom 61.6% were male. The highest proportion of studies, almost half, were in
      children with syndromes (44.4%), followed by studies in children with
      intellectual disabilities (18.9%). Non-pharmacological sleep management was
      primarily aimed at improving sleep quality (86.7%), followed by sleep-wake
      schedules and, to a certain extent, sleep regularity (42.2%). About 56.7% of the
      studies reported more than one approach. Studies mostly focused on disorders of
      initiating and maintaining sleep through a diversity of strategies and relied
      heavily on subjective measures to identify and monitor problematic sleeping.
      Sleep management approaches were primarily delivered at the level of the
      individual in the home setting. The number of management approaches per study was
      unrelated to the number of sleep problems discussed. INTERPRETATION: Modifying
      sleep management strategies to meet the specific needs of children with
      developmental disabilities is encouraged, and studies that look beyond sleep
      quality or sleep quantity are required. It is also advocated that modifications
      to sleep hygiene, sleep regularity, and sleep ecology in a population with
      developmental disabilities are rigorously investigated. Finally, daytime
      somnolence should not be overlooked when aiming to optimize sleep in children
      with developmental disabilities across the ages and stages of their lives. There
      were several limitations in the research findings of problematic sleep in
      children with developmental disabilities. In general, the sleep problems and the
      developmental disabilities investigated were multicomponent in nature. It is
      likely that management approaches impacted those problems on multiple levels or
      through diverse 'therapeutic' pathways. There is a need for randomized controlled
      trials and more objective measures that quantify improved sleep or wake states.

PMID- 25370593
TI  - Cognitive function in the prefrailty and frailty syndrome.
AB  - OBJECTIVES: To explore the relationship between cognitive function and frailty.
      DESIGN: A cross-sectional study using data from Wave 1 of The Irish Longitudinal
      Study on Ageing, a population representative study of adults aged 50 and older in
      the Republic of Ireland. SETTING: Community-dwelling adults completed a home- or
      health center-based nurse-led assessment. PARTICIPANTS: Individuals aged 50 and
      older without a history of stroke, Parkinson's disease, or severe cognitive
      impairment (Mini-Mental State Examination (MMSE) score <18) and not taking
      antidepressants (N = 4,649). MEASUREMENTS: A cognitive battery including MMSE,
      Montreal Cognitive Assessment, Color Trails Test, Cambridge Mental Disorders of
      the Elderly Examination memory and executive function subtests, 10-word recall,
      Sustained Attention to Response Task, and choice reaction time was used to
      generate composite scores of cognitive domains. Frailty was assessed according to
      weakness, slowness, exhaustion, low physical activity, and weight loss. RESULTS:
      After full adjustment, cognitive function across all domains except self-rated
      memory and processing speed was significantly worse in prefrail and frail
      participants (P < .05) than in those who were robust. Weakness and walking speed
      were most consistently linked to poorer cognition, whereas low activity and
      weight loss were not independently associated with any cognitive domain.
      Exhaustion was associated with global cognition (B = -0.18 +/- 0.06), with some
      evidence of links to objectively measured and self-rated memory. CONCLUSION:
      Cognitive function is worse across multiple cognitive domains in prefrail and
      frail individuals aged 50 and older than in those who are robust, although the
      absolute differences are small after adjusting for confounding factors.

PMID- 25370594
TI  - Light-reducible dissipative nanostructures formed at the solid-liquid interface.
AB  - Dissipative structures are macroscopic or even larger ordered structures that
      emerge under conditions far from thermodynamic equilibrium. In contrast,
      molecular self-assembly has been investigated near at the thermodynamic
      equilibrium, which provides basically smaller, nano-to-micron sized structures.
      In terms of the formation principles, there exists an essential gap between the
      dissipative structures and molecular self-assemblies. To fill this gap, molecular
      self-assembly of light-reducible organic-inorganic ion pairs was investigated
      under far-from-equilibrium conditions. When solid films of tetraalkylammonium
      hexafluorophosphate were immersed in aqueous Au(OH)4(-) and immediately
      photoirradiated, gold nanowires are formed at the solid-aqueous interface. On the
      other hand, such nanowires were not formed when the photoirradiation was
      conducted for the specimens after a prolonged immersion period of 60 min. These
      observations indicate spontaneous growth of dissipative nanofibrous self
      assemblies consisting of light-reducible ion pairs [tetraalkylammonium
      ion][Au(OH)4(-)] at the interface and their photoreduction to give developed
      nanowires. These nanowires are not available by the photoreduction of Au(OH)4(-)
      ions under conditions near at the thermodynamic equilibrium. A picture for the
      dissipative nanostructures is obtained: the formation of amphiphilic light
      reducible nanowire structures is based on the static self-assembly near at the
      thermodynamic equilibrium, whereas their spontaneous, anisotropic growth from the
      interface to the aqueous phase is directed by dynamic, dissipative self-assembly
      phenomena under the far-from-equilibrium conditions. Thus, the both elements of
      dissipative self-assembly (dynamic) and static molecular self-assembly fuse
      together at the nanoscale, which is an essential feature of the dissipative
      nanostructures. 

PMID- 25370595
TI  - Efficacy of corticosteroids for cancer-related fatigue: A pilot randomized
      placebo-controlled trial of advanced cancer patients.
AB  - OBJECTIVE: Cancer-related fatigue (CRF) is a common and one of the most important
      issues in palliative medicine, and it has been demonstrated to have a significant
      impact on patient quality of life (QoL). The present pilot randomized controlled
      study evaluated the efficacy and toxicity of methylprednisolone (MP) for CRF in
      advanced cancer patients. METHOD: Our study was planned as a randomized, double
      blind, multicenter, placebo-controlled trial. Patients were randomly assigned to
      an MP group, who received 32 mg/day of MP orally for 7 days, and a placebo group.
      The primary endpoint was an improvement in visual analog scale (VAS) score for
      fatigue from baseline to day 7. The secondary endpoints were improvements in
      appetite loss and QoL as well as evaluating the safety of corticosteroids as
      palliative therapy. RESULTS: It was not possible to complete patient
      registration. In total, 35 patients were randomly assigned to an MP group (n =
      18) and a placebo group (n = 17). The mean changes in VAS score for fatigue were 
      9.06 in the placebo group and -1.56 in the MP group, and for appetite loss -6.44
      in the placebo group and -8.06 in the MP group. In addition, there was no
      evidence that methylprednisolone improved appetite loss or QoL compared to
      placebo. The incidence of adverse effects was not greater in the MP group.
      Significant of Result: We conclude that our sample size was too small to prove
      the efficacy of methylprednisolone in improving fatigue. Our results were
      reported as a pilot study performed to support a subsequent larger trial.

PMID- 25370596
TI  - Dynamic piezoelectric stimulation enhances osteogenic differentiation of human
      adipose stem cells.
AB  - This work reports on the influence of the substrate polarization of electroactive
      beta-poly(vinylidene fluoride) (beta-PVDF) on human adipose stem cells (hASCs)
      differentiation under static and dynamic conditions. hASCs were cultured on
      different beta-PVDF surfaces (non-poled and "poled -") adsorbed with fibronectin
      and osteogenic differentiation was determined using a quantitative alkaline
      phosphatase assay. "Poled -" beta-PVDF samples promote higher osteogenic
      differentiation, which is even higher under dynamic conditions. It is thus
      demonstrated that electroactive membranes can provide the necessary
      electromechanical stimuli for the differentiation of specific cells and therefore
      will support the design of suitable tissue engineering strategies, such as bone
      tissue engineering.

PMID- 25370598
TI  - Vision in a phase 3 trial of natalizumab for multiple sclerosis: relation to
      disability and quality of life.
AB  - BACKGROUND: Low-contrast visual acuity (LCVA), a sensitive measure of visual
      function in multiple sclerosis (MS), demonstrated treatment effects as a
      secondary outcome measure in the Phase 3 trial of natalizumab, AFFIRM. In these
      posttrial analyses, we studied the relation of visual function to quality of life
      (QOL), magnetic resonance imaging (MRI) measures, and Expanded Disability Status
      Scale (EDSS) scores. METHODS: At baseline and at 52 and 104 weeks in AFFIRM,
      patients underwent binocular testing of LCVA (1.25% and 2.5% contrast) and high
      contrast visual acuity (HCVA). Vision-specific QOL was assessed by the Impact of
      Visual Impairment Scale (IVIS), whereas the SF-36 Health Survey and Visual Analog
      Scale were administered as generic QOL measures and the EDSS as a measure of
      neurologic impairment. RESULTS: Among QOL measures, IVIS scores showed the most
      significant correlations with visual dysfunction at all time points in the trial
      (r= -0.25 to -0.45, P < 0.0001 for LCVA and HCVA). Higher MRI T1- and T2-lesion
      volumes were also associated with worse vision scores at all time points (P <
      0.0001). Clinically meaningful worsening (progression) of LCVA was noted in
      substantial proportions of patients in AFFIRM and was prevalent even among those
      without EDSS progression over 2 years (21.9% with LCVA progression at 2.5%
      contrast; 26.2% at 1.25% contrast). HCVA worsened in only 3.7% of patients
      without EDSS progression. CONCLUSIONS: Loss of visual function, particularly as
      measured by LCVA, was common in AFFIRM, occurring in >20% of patients. Both LCVA
      and HCVA scores reflect vision-specific aspects of QOL, but LCVA provides
      information about disability progression not entirely captured by the EDSS.
      Vision represents a key dimension of outcome assessment for MS and adds valuable
      information on disability and QOL that can be useful to clinicians.

PMID- 25370597
TI  - Association of urine alpha1-microglobulin with kidney function decline and
      mortality in HIV-infected women.
AB  - BACKGROUND AND OBJECTIVES: Despite advances in therapy, HIV-infected individuals
      remain at higher risk for kidney dysfunction than uninfected individuals. It was
      hypothesized that urine levels of alpha1-microglobulin, a biomarker of proximal
      tubular dysfunction, would predict kidney function decline and mortality risk in
      HIV-infected and uninfected women. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      In the Women's Interagency HIV Study, urine alpha1-microglobulin and creatinine
      concentrations were measured in 903 HIV-infected and 287 uninfected women using
      stored urine from 1999 to 2000, when prevalence of tenofovir use was <1%.
      Participants were categorized into three categories by level of alpha1
      microglobulin-to-creatinine ratio, and associations with kidney decline and all
      cause mortality over 8 years were evaluated. RESULTS: Urine alpha1-microglobulin
      was detectable in 60% of HIV-infected and 40% of uninfected women (P<0.001).
      Among HIV-infected women, there were 177 (22%), 61 (7%), and 128 (14%) patients
      with incident CKD, with 10% annual eGFR decline, and who died, respectively.
      Compared with HIV-infected women in the lowest alpha1-microglobulin category, HIV
      infected women in the highest alpha1-microglobulin category had a 2.1-fold risk
      of incident CKD (95% confidence interval, 1.3 to 3.4), 2.7-fold risk of 10%
      annual eGFR decline (95% confidence interval, 1.2 to 5.9), and 1.6-fold mortality
      risk (95% confidence interval, 1.0 to 2.6) in models adjusting for kidney risk
      factors, baseline eGFR, and albuminuria. Among uninfected women, the highest
      alpha1-microglobulin category was associated with 3% (relative risk, 2.2; 95%
      confidence interval, 1.4 to 3.5) and 5% (relative risk, 2.2; 95% confidence
      interval, 1.1 to 4.3) annual eGFR decline relative to the lowest alpha1
      microglobulin category. CONCLUSIONS: Proximal tubular dysfunction, indicated by
      urine alpha1-microglobulin, was independently associated with kidney function
      decline in HIV-infected and uninfected women and mortality risk among HIV
      infected women.

PMID- 25370599
TI  - Worsening of renal function during 1 year after hospital discharge is a strong
      and independent predictor of all-cause mortality in acute decompensated heart
      failure.
AB  - BACKGROUND: Renal impairment is a common comorbidity and the strongest risk
      factor for poor prognosis in acute decompensated heart failure (ADHF). In
      clinical practice, renal function is labile during episodes of ADHF, and often
      worsens after discharge. The significance of worsening of renal function (WRF)
      after discharge has not been investigated as extensively as baseline renal
      function at admission or WRF during hospitalization. METHODS AND RESULTS: Among
      611 consecutive patients with ADHF emergently admitted to our hospital, 233
      patients with 3 measurements of serum creatinine (SCr) level measurements (on
      admission, at discharge, and 1 year after discharge) were included in the present
      study. Patients were divided into 2 groups according to the presence or absence
      of WRF at 1 year after discharge (1y-WRF), defined as an absolute increase in SCr
      >0.3 mg/dL (>26.5 MUmol/L) plus a >=25% increase in SCr at 1 year after discharge
      compared to the SCr value at discharge. All-cause and cardiovascular mortality
      were assessed as adverse outcomes. During a mean follow-up of 35.4 months, 1y-WRF
      occurred in 48 of 233 patients. There were 66 deaths from all causes. All-cause
      and cardiovascular mortality were significantly higher in patients with 1y-WRF
      (log-rank P<0.0001 and P<0.0001, respectively) according to Kaplan-Meier
      analysis. In a multivariate Cox proportional hazards model, 1y-WRF was a strong
      and independent predictor of all-cause and cardiovascular mortality. Hemoglobin
      and B-type natriuretic peptide at discharge, as well as left ventricular ejection
      fraction <50%, were independent predictors of 1y-WRF. CONCLUSIONS: In patients
      with ADHF, 1y-WRF is a strong predictor of all-cause and cardiovascular
      mortality.

PMID- 25370600
TI  - Quality of information available via the internet for patients with head and neck
      cancer: are we improving?
AB  - This study aimed to evaluate the type, content, accessibility and quality of
      information available via the internet for patients with head and neck cancer.
      The Google search engine was used to generate lists of the first 100 websites for
      general head and neck cancer and the first ten for head and neck cancers by
      anatomical location (160 total). Websites were evaluated with the validated
      DISCERN and LIDA instruments, the SMOG (Simple measure of gobbledygook)
      readability score and against the JAMA (Journal of the American Medical
      Association) criteria. 40 of the 160 websites ranked by Google were suitable for
      analysis. Seven websites (17.5%) partially or fully achieved all four JAMA
      benchmarks and only one (2.5%) site achieved none. 28 (70%) included reference to
      quality of life factors. Correlations were identified between Google site rank
      and all four of our appraisal tools; LIDA (-0.966, p = 0.006), JAMA (-5.93, p =
      0.028), DISCERN (-0.568, p = 0.037) and SMOG (4.678, p = 0.04). Google site rank
      and both government run sites (-35.38, p = 0.034) and sites run by universities
      or hospitals (-27.32, p = 0.016) also showed an association. Comparing our
      observations with those of Riordain in 2008, there has been little improvement in
      the quality of head and neck cancer information available online over this time.
      Given the variability in quality of information online, patients would benefit
      from being directed to reliable websites by clinicians.

PMID- 25370601
TI  - The effects of oropharyngeal-lingual exercises in patients with primary snoring.
AB  - Primary snoring (PS) is one of the sleep breathing disorders with suboptimal
      results of treatment. It is recommended that Oropharyngeal exercises can be a
      therapeutic choice for the patients with mild to moderate degrees of PS. We
      assessed the effects of oropharyngeal-lingual (OPL) exercises on patients with
      primary snoring (PS) referred to Amiralmomenin University Hospital, Rasht, Iran
      in 2012. Fifty-three patients with PS underwent the sets of OPL exercises for 3
      months, 5 days a week, and 30 min a day under the supervision of a speech
      therapist. Severity of the snoring was assessed by use of Visual Analogue Scale
      (VAS) and Snoring Scale Score (SSS) criteria before and after the exercises, and
      data were analyzed using SPSS version 17. Mean SSS before the study was 7.01 +/-
      1.72, while it was 3.09 +/- 2.7 after the study; and the mean VAS scores were
      8.54 +/- 1.89 and 4.69 +/- 2.94 before and after the study, respectively (P =
      0.0001). There was a significant relationship between having conflicts with
      roommates (P = 0.0001), duration of snoring occurrence (P = 0.0001), severity of
      snoring (P = 0.0001) before and after the intervention. In conclusion, doing the
      OPL exercises significantly decreases the severity of PS. 

PMID- 25370602
TI  - Differentiation potential of human bone marrow mesenchymal stem cells into
      motorneuron-like cells on electrospun gelatin membrane.
AB  - Human bone marrow-derived mesenchymal stem cells are potent types of cells with
      self renewal ability and immunomodulatory properties. They not only have the
      capacity to differentiate into mesodermal lineages, but they are also capable to
      transdifferentiate into neural cells in vitro and in vivo. From a biological
      point of view, the specification of cell fate in the central nervous system is
      largely dictated by retinoic acid and sonic hedgehog. In addition with inductive
      molecules, electrospun three dimensional (3D) scaffolds with similar properties
      to natural extracellular matrix represent a physiological environment that could
      better resemble the in vivo microenvironment in comparison with two dimensional
      culture systems. In this regard, the aim of this study was to examine whether
      induction of human BM-MSCs with retinoic acid (RA) and sonic hedgehog (Shh) in
      combination with electrospun gelatin scaffold could lead to better
      differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs)
      into motorneuron-like cells in vitro. 

PMID- 25370603
TI  - The role of Ca2+ influx in endocytic vacuole formation in pancreatic acinar
      cells.
AB  - The inducers of acute pancreatitis trigger a prolonged increase in the cytosolic
      Ca(2+) concentration ([Ca(2+)]c), which is responsible for the damage to and
      eventual death of pancreatic acinar cells. Vacuolization is an important
      indicator of pancreatic acinar cell damage. Furthermore, activation of
      trypsinogen occurs in the endocytic vacuoles; therefore the vacuoles can be
      considered as 'initiating' organelles in the development of the cell injury. In
      the present study, we investigated the relationship between the formation of
      endocytic vacuoles and Ca(2+) influx developed in response to the inducers of
      acute pancreatitis [bile acid taurolithocholic acid 3-sulfate (TLC-S) and
      supramaximal concentration of cholecystokinin-8 (CCK)]. We found that the
      inhibitor of STIM (stromal interaction molecule)/Orai channels, GSK-7975A,
      effectively suppressed both the Ca(2+) influx (stimulated by inducers of
      pancreatitis) and the formation of endocytic vacuoles. Cell death induced by TLC
      S or CCK was also inhibited by GSK-7975A. We documented the formation of
      endocytic vacuoles in response to store-operated Ca(2+) entry (SOCE) induced by
      thapsigargin [TG; inhibitor of sarcoplasmic/endoplasmic reticulum (ER) Ca(2+)
      pumps] and observed strong inhibition of TG-induced vacuole formation by GSK
      7975A. Finally, we found that structurally-unrelated inhibitors of calpain
      suppress formation of endocytic vacuoles, suggesting that this Ca2+-dependent
      protease is a mediator between Ca(2+) elevation and endocytic vacuole formation.

PMID- 25370604
TI  - Is there a moral obligation to select healthy children?
AB  - Reproductive decision-making in the post-genetic age is a minefield of complex
      ethical problems. One such problem centres on whether there is an obligation on
      reproducers to choose the best possible child. This paper focusses on a
      simplified scenario: there are two embryos to choose from, one of which will
      develop a condition that diminishes quality of life but would still have 'a life
      worth living', the other of which is normal. Is there an obligation to choose the
      healthier child? If so, what is the nature and scope of this obligation? The
      answer to these questions relies on a satisfactory answer to the non-identity
      problem (NIP). This paper explores several solutions to the NIP and argues for a
      solution grounded in the concept of harm. Various accounts of harm are discussed
      and synthesised to provide a new 'comparative bad state view' of harm. This
      account is used to justify the obligation to choose the healthier child. How far
      should this obligation go? This paper rejects the conservative position of
      'procreative autonomy' - which holds that such obligations have no place in
      reproductive decisions - and the radical position of 'procreative beneficence' -
      which holds that there is an even stronger obligation to make the best possible
      child. The obligation to choose the healthier child may be over-ridden by
      countervailing reasons; the moral calculus in any individual case will be largely
      dependent on the expected quality of life of the child. 

PMID- 25370605
TI  - Thermally assisted electric field control of magnetism in flexible multiferroic
      heterostructures.
AB  - Thermal and electrical control of magnetic anisotropy were investigated in
      flexible Fe81Ga19 (FeGa)/Polyvinylidene fluoride (PVDF) multiferroic
      heterostructures. Due to the large anisotropic thermal deformation of PVDF
      (alpha1 = -13 * 10(-6) K(-1) and alpha2 = -145 * 10(-6) K(-1)), the in-plane
      uniaxial magnetic anisotropy (UMA) of FeGa can be reoriented 90 degrees  by
      changing the temperature across 295 K where the films are magnetically isotropic.
      Thus, the magnetization of FeGa can be reversed by the thermal cycling between
      280 and 320 K under a constant magnetic field lower than coercivity. Moreover,
      under the assistance of thermal deformation with slightly heating the samples to
      the critical temperature, the electric field of +/- 267 kV cm(-1) can well align
      the UMA along the two orthogonal directions. The new route of combining thermal
      and electrical control of magnetic properties realized in PVDF-based flexible
      multiferroic materials shows good prospects in application of flexible thermal
      spintronic devices and flexible microwave magnetic materials.

PMID- 25370606
TI  - Artesunate inhibits proliferation of naive CD4(+) T cells but enhances function
      of effector T cells.
AB  - Artesunate is an artemisinin derivative from Artemisia annua and is being applied
      as a first-line drug for malaria treatment. In addition to anti-malarial effects,
      anti-cancer, anti-viral, and anti-inflammatory activities have been reported for
      artemisinin derivatives. In this study, we investigated the effects of artesunate
      on naive T cell activation and Th1/Th2 differentiation. Artesunate inhibited the
      proliferation of CD4(+) T cells and the production of IL-2, T cell growth factor.
      Moreover, artesunate reduced the expression of cell surface protein CD25 (IL-2
      receptor alpha chain) and CD69 on CD4(+) T cells. Artesunate showed inhibitory
      effects on naive T cell activation but artesunate increased the production of IFN
      gamma and IL-4 under Th1 and Th2 skewed condition respectively. Therefore, these
      results suggest that artesunate has a negative mitogenic effect on CD4(+) T cells
      but reinforces the function of effector T cells. 

PMID- 25370608
TI  - Penipyrols A-B and peniamidones A-D from the mangrove derived Penicillium solitum
      GWQ-143.
AB  - Chemical investigation the extract of Penicillium solitum GWQ-143 led to yield
      four new compounds penipyrols A-B (1-2) and peniamidones A-B (3-4), together with
      peniamidones C-D (5-6), which had been previously described as synthetic
      intermediates, not obtained from natural resource. The structures of those new
      compounds were established through extensive spectroscopic analysis. Compounds 1
      6 exhibited great radical scavenging activities against DPPH with IC50 values
      ranged from 4.7 to 15.0 MUM.

PMID- 25370607
TI  - Anti-inflammatory effects of Dendrobium nobile derived phenanthrenes in LPS
      stimulated murine macrophages.
AB  - Dendrobium nobile belongs to the Orchidaceae family and is one of the medicinal
      herbs used in traditional Chinese medicine as a therapeutic agent for
      gastrointestinal and cardiovascular diseases. In this study, we separated three
      phenanthrenes (ephemeranthol A (EA), 1,5,7-trimethoxyphenanthren-2-ol (TP),
      dehydroorchinol (DO)) from D. nobile, and compared their anti-inflammatory
      activities. TP is a new phenanthrene compound and its structure was determined
      from (1)H, (13)C NMR and HR-ESI-MS data. To analyze the anti-inflammatory
      activities of the phenanthrenes, Raw 264.7 cells were used, since they are
      immature-macrophages and easily matured by LPS stimulation. EA and DO showed anti
      inflammatory activities in the activated Raw 264.7 cells. That is, we showed that
      EA is a potent inhibitor of the production of nitric oxide and pro-inflammatory
      cytokines. The inhibitory activities of phenanthrenes were found to be caused by
      blockage of NF-kappaB activation and the phosphorylation of MAP kinases in the
      macrophages. These results are expected to serve as a guide for future studies on
      the ability of phenanthrenes to inhibit acute and chronic inflammatory diseases. 

PMID- 25370609
TI  - Erratum to: Antiviral activity of Bifidobacterium adolescentis SPM 0214 against
      Herpes Simplex Virus Type 1.

PMID- 25370610
TI  - Acetyl- and butyryl-cholinesterase inhibitory activities of the edible brown alga
      Eisenia bicyclis.
AB  - As part of our ongoing isolation of cholinesterase (ChE) inhibitors from natural
      marine sources, the bioactivity of the ethanolic extracts from 12 Korean seaweeds
      were screened for their inhibitory activities against acetylcholinesterase
      (AChE), butyrylcholinesterase (BChE), and total reactive oxygen species (ROS)
      generation. Eisenia bicyclis exhibited promising inhibitory properties against
      AChE, BChE and total ROS with inhibition percentages (%) of 68.01 +/- 1.37, 95.72
      +/- 3.80, and 73.20 +/- 1.82 at concentrations of 25 ug/mL, respectively. Among
      the different solvent-soluble fractions obtained from the ethanolic extract, the
      ethyl acetate (EtOAc) fraction was found to cause the most potent scavenging, or
      inhibitory activities, against 2,2-diphenyl-1-picrylhydrazyl (DPPH),
      peroxynitrite (ONOO(-)) and total ROS with the respective IC50 values of 2.48 +/-
      0.01, 8.70 +/- 0.06, and 0.81 +/- 0.03 ug/mL. Likewise, the EtOAc fraction also
      exhibited potent inhibitory activities against AChE and BChE with IC50 values of
      2.78 +/- 0.07 and 3.48 +/- 0.32 ug/mL, respectively. Silica gel column
      chromatography of the EtOAc fraction yielded a phlorotannin, 974-B, based on the
      comparison with reported (1)H- and (13)C-NMR spectroscopic data. 974-B showed
      strong scavenging/or inhibitory potential against DPPH, ONOO(-), total ROS, AChE,
      and BChE with the respective IC50 values of 0.86 +/- 0.02, 1.80 +/- 0.01, 6.45 +/
      0.04, 1.95 +/- 0.01, and 3.26 +/- 0.08 uM, respectively. These results indicate
      that the potential of E. bicyclis and its phlorotannin for use in the development
      of therapeutic or preventive agents of Alzheimer's disease mainly through ChE
      inhibition and additional antioxidant capacities.

PMID- 25370611
TI  - Comparative essential oil composition of aerial parts of Tanacetum dumosum Boiss.
      from Southern Zagros, Iran.
AB  - The essential oils of leaves and flowers of Tanacetum dumosum Boiss., an endemic
      medicinal shrub, were extracted by using hydrodistillation method and analysed
      using GC and GC-MS. A total of 43 and 44 compounds were identified in the
      essential oils from the leaves and flowers of T. dumosum, respectively. The major
      chemical constituents of leaves oil were borneol (27.9%), bornyl acetate (18.4%),
      1,8-cineol (17.5%), alpha-terpineol (5.3%), cis-chrysanthenyl acetate (3.3%),
      camphene (2.7%) and terpinene-4-ol (1.9%), while the main components of the
      flower oil were isobornyl-2-methyl butanoate (41.1%), trans-linalyl oxide acetate
      (11.9%), 1,8-cineole (7.7%), thymol (4.2%), linalool (3.9%), camphor (2.9%),
      isobornyl propanoate (2.9%), alpha-terpineol (2.1%) and caryophyllene oxide
      (2.0%). Major qualitative and quantitative variations for some main chemical
      compounds among different aerial parts of T. dumosum were identified. High
      contents of borneol, bornyl acetate, 1,8-cineol and linalool in the leaves and
      flowers of T. dumosum show its potential for use in the food and perfumery
      industry. 

PMID- 25370612
TI  - Using biomaterials to study stem cell mechanotransduction, growth and
      differentiation.
AB  - Self-renewal and differentiation are two fundamental characteristics of stem
      cells. Stem cell self-renewal is critical for replenishing the stem cell
      population, while differentiation is necessary for maintaining tissue
      homeostasis. Over the last two decades a great deal of effort has been applied to
      discovering the processes that control these opposing stem cell fates. One way of
      examining the role of the physical environment is the use of biomaterial
      strategies that have the ability to manipulate cells without any requirement for
      chemical factors. The mechanism whereby cells have been found to respond to a
      mechanical stimulus is termed mechanotransduction, the process by which a
      mechanical cue (or alteration in cell spreading changing internal cellular
      mechanics, i.e. intracellular tension) is transduced into a chemical signal
      inside the cell, eliciting changes in gene expression. This can occur either
      directly, as a result of changes in the cell cytoskeleton, or indirectly through
      a series of biochemical signalling cascades. The main focus of this review is to
      examine the role of mechanotransduction in the differentiation and self-renewal
      of stem cells. In particular, we will focus on the use of biomaterials as a tool
      for examining mechanotrandsuctive effects on self-renewal and differentiation.

PMID- 25370613
TI  - Point/Counterpoint. MRI/CT is the future of radiotherapy treatment planning.

PMID- 25370614
TI  - Thermoacoustic imaging over large field of view for three-dimensional breast
      tumor localization: a phantom study.
AB  - PURPOSE: Previous studies demonstrated that thermoacoustic imaging (TAI) has
      great potential for breast tumor detection. However, large field of view (FOV)
      imaging remains a long-standing challenge for three-dimensional (3D) breast tumor
      localization. Here, the authors propose a practical TAI system for noninvasive 3D
      localization of breast tumors with large FOV through the use of ultrashort
      microwave pulse (USMP). METHODS: A USMP generator was employed for TAI. The
      energy density required for quality imaging and the corresponding microwave-to
      acoustic conversion efficiency were compared with that of conventional TAI. The
      microwave energy distribution, imaging depth, resolution, and 3D imaging
      capabilities were then investigated. Finally, a breast phantom embedded with a
      laboratory-grown tumor was imaged to evaluate the FOV performance of the USMP TAI
      system, under a simulated clinical situation. RESULTS: A radiation energy density
      equivalent to just 1.6%-2.2% of that for conventional submicrosecond microwave
      TAI was sufficient to obtain a thermoacoustic signal with the required signal-to
      noise ratio. This result clearly demonstrated a significantly higher microwave-to
      acoustic conversion efficiency of USMP TAI compared to that of conventional TAI.
      The USMP TAI system achieved 61 mm imaging depth and 12 * 12 cm(2) microwave
      radiation area. The volumetric image of a copper target measured at depth of 4-6
      cm matched well with the actual shape and the resolution reaches 230 MUm. The TAI
      of the breast phantom was precisely localized to an accuracy of 0.1 cm over an 8
      * 8 cm(2) FOV. CONCLUSIONS: The experimental results demonstrated that the USMP
      TAI system offered significant potential for noninvasive clinical detection and
      3D localization of deep breast tumors, with low microwave radiation dose and high
      spatial resolution over a sufficiently large FOV.

PMID- 25370615
TI  - Monte Carlo calculations of electron beam quality conversion factors for several
      ion chamber types.
AB  - PURPOSE: To provide a comprehensive investigation of electron beam reference
      dosimetry using Monte Carlo simulations of the response of 10 plane-parallel and
      18 cylindrical ion chamber types. Specific emphasis is placed on the
      determination of the optimal shift of the chambers' effective point of
      measurement (EPOM) and beam quality conversion factors. METHODS: The EGSnrc
      system is used for calculations of the absorbed dose to gas in ion chamber models
      and the absorbed dose to water as a function of depth in a water phantom on which
      cobalt-60 and several electron beam source models are incident. The optimal EPOM
      shifts of the ion chambers are determined by comparing calculations of R50
      converted from I50 (calculated using ion chamber simulations in phantom) to R50
      calculated using simulations of the absorbed dose to water vs depth in water.
      Beam quality conversion factors are determined as the calculated ratio of the
      absorbed dose to water to the absorbed dose to air in the ion chamber at the
      reference depth in a cobalt-60 beam to that in electron beams. RESULTS: For most
      plane-parallel chambers, the optimal EPOM shift is inside of the active cavity
      but different from the shift determined with water-equivalent scaling of the
      front window of the chamber. These optimal shifts for plane-parallel chambers
      also reduce the scatter of beam quality conversion factors, kQ, as a function of
      R50. The optimal shift of cylindrical chambers is found to be less than the 0.5
      rcav recommended by current dosimetry protocols. In most cases, the values of the
      optimal shift are close to 0.3 rcav. Values of kecal are calculated and compared
      to those from the TG-51 protocol and differences are explained using accurate
      individual correction factors for a subset of ion chambers investigated. High
      precision fits to beam quality conversion factors normalized to unity in a beam
      with R50 = 7.5 cm (kQ (')) are provided. These factors avoid the use of gradient
      correction factors as used in the TG-51 protocol although a chamber dependent
      optimal shift in the EPOM is required when using plane-parallel chambers while no
      shift is needed with cylindrical chambers. The sensitivity of these results to
      parameters used to model the ion chambers is discussed and the uncertainty
      related to the practical use of these results is evaluated. CONCLUSIONS: These
      results will prove useful as electron beam reference dosimetry protocols are
      being updated. The analysis of this work indicates that cylindrical ion chambers
      may be appropriate for use in low-energy electron beams but measurements are
      required to characterize their use in these beams.

PMID- 25370616
TI  - Dosimetry of cone-defined stereotactic radiosurgery fields with a commercial
      synthetic diamond detector.
AB  - PURPOSE: Small field x-ray beam dosimetry is difficult due to lack of lateral
      electronic equilibrium, source occlusion, high dose gradients, and detector
      volume averaging. Currently, there is no single definitive detector recommended
      for small field dosimetry. The objective of this work was to evaluate the
      performance of a new commercial synthetic diamond detector, namely, the PTW 60019
      microDiamond, for the dosimetry of small x-ray fields as used in stereotactic
      radiosurgery (SRS). METHODS: Small field sizes were defined by BrainLAB circular
      cones (4-30 mm diameter) on a Novalis Trilogy linear accelerator and using the 6
      MV SRS x-ray beam mode for all measurements. Percentage depth doses (PDDs) were
      measured and compared to an IBA SFD and a PTW 60012 E diode. Cross profiles were
      measured and compared to an IBA SFD diode. Field factors, OmegaQclin,Qmsr
      (fclin,fmsr) , were calculated by Monte Carlo methods using BEAMnrc and
      correction factors, kQclin,Qmsr (fclin,fmsr) , were derived for the PTW 60019
      microDiamond detector. RESULTS: For the small fields of 4-30 mm diameter, there
      were dose differences in the PDDs of up to 1.5% when compared to an IBA SFD and
      PTW 60012 E diode detector. For the cross profile measurements the penumbra
      values varied, depending upon the orientation of the detector. The field factors,
      OmegaQclin,Qmsr (fclin,fmsr) , were calculated for these field diameters at a
      depth of 1.4 cm in water and they were within 2.7% of published values for a
      similar linear accelerator. The corrections factors, kQclin,Qmsr (fclin,fmsr) ,
      were derived for the PTW 60019 microDiamond detector. CONCLUSIONS: The authors
      conclude that the new PTW 60019 microDiamond detector is generally suitable for
      relative dosimetry in small 6 MV SRS beams for a Novalis Trilogy linear equipped
      with circular cones.

PMID- 25370617
TI  - End-to-end test of spatial accuracy in Gamma Knife treatments for trigeminal
      neuralgia.
AB  - PURPOSE: Spatial accuracy is most crucial when small targets like the trigeminal
      nerve are treated. Although current quality assurance procedures typically verify
      that individual apparatus, like the MRI scanner, CT scanner, Gamma Knife, etc.,
      are meeting specifications, the cumulative error of all equipment and procedures
      combined may exceed safe margins. This study uses an end-to-end approach to
      assess the overall targeting errors that may have occurred in individual patients
      previously treated for trigeminal neuralgia. METHODS: The trigeminal nerve is
      simulated by a 3 mm long, 3.175 mm (1/8 in.) diameter MRI-contrast filled cavity
      embedded within a PMMA plastic capsule. The capsule is positioned within the head
      frame such that the location of the cavity matches the Gamma Knife coordinates of
      an arbitrarily chosen, previously treated patient. Gafchromic EBT2 film is placed
      at the center of the cavity in coronal and sagittal orientations. The films are
      marked with a pinprick to identify the cavity center. Treatments are planned for
      radiation delivery with 4 mm collimators according to MRI and CT scans using the
      clinical localizer boxes and acquisition protocols. Shots are planned so that the
      50% isodose surface encompasses the cavity. Following irradiation, the films are
      scanned and analyzed. Targeting errors are defined as the distance between the
      pinprick, which represents the intended target, and the centroid of the 50%
      isodose line, which is the center of the radiation field that was actually
      delivered. RESULTS: Averaged over ten patient simulations, targeting errors along
      the x, y, and z coordinates (patient's left-to-right, posterior-to-anterior, and
      head-to-foot) were, respectively, -0.060 +/- 0.363, -0.350 +/- 0.253, and 0.348
      +/- 0.204 mm when MRI was used for treatment planning. Planning according to CT
      exhibited generally smaller errors, namely, 0.109 +/- 0.167, -0.191 +/- 0.144,
      and 0.211 +/- 0.094 mm. The largest errors along individual axes in MRI- and CT
      planned treatments were, respectively, -0.761 mm in the y-direction and 0.428 mm
      in the x-direction, well within safe limits. CONCLUSIONS: The highly accurate
      dose delivery was possible because the Gamma Knife, MRI scanner, and other
      equipment performed within tight limits and scans were acquired using the
      thinnest slices and smallest pixel sizes available. Had the individual devices
      performed only near the limits of their specifications, the cumulative error
      could have left parts of the trigeminal nerve undertreated. The presented end-to
      end test gives assurance that patients had received the expected high quality
      treatment. End-to-end tests should become part of clinical practice.

PMID- 25370618
TI  - Evaluation of potential internal target volume of liver tumors using cine-MRI.
AB  - PURPOSE: Four-dimensional computed tomography (4DCT) is widely used for
      evaluating moving tumors, including lung and liver cancers. For patients with
      unstable respiration, however, the 4DCT may not visualize tumor motion properly.
      High-speed magnetic resonance imaging (MRI) sequences (cine-MRI) permit direct
      visualization of respiratory motion of liver tumors without considering radiation
      dose exposure to patients. Here, the authors demonstrated a technique for
      evaluating internal target volume (ITV) with consideration of respiratory
      variation using cine-MRI. METHODS: The authors retrospectively evaluated six
      patients who received stereotactic body radiotherapy (SBRT) to hepatocellular
      carcinoma. Before acquiring planning CT, sagittal and coronal cine-MRI images
      were acquired for 30 s with a frame rate of 2 frames/s. The patient
      immobilization was conducted under the same condition as SBRT. Planning CT images
      were then acquired within 15 min from cine-MRI image acquisitions, followed by a
      4DCT scan. To calculate tumor motion, the motion vectors between two continuous
      frames of cine-MRI images were calculated for each frame using the pyramidal
      Lucas-Kanade method. The target contour was delineated on one frame, and each
      vertex of the contour was shifted and copied onto the following frame using
      neighboring motion vectors. 3D trajectory data were generated with the centroid
      of the contours on sagittal and coronal images. To evaluate the accuracy of the
      tracking method, the motion of clearly visible blood vessel was analyzed with the
      motion tracking and manual detection techniques. The target volume delineated on
      the 50% (end-exhale) phase of 4DCT was translated with the trajectory data, and
      the distribution of the occupancy probability of target volume was calculated as
      potential ITV (ITV Potential). The concordance between ITV Potential and ITV
      estimated with 4DCT (ITV 4DCT) was evaluated using the Dice's similarity
      coefficient (DSC). RESULTS: The distance between blood vessel positions
      determined with motion tracking and manual detection was analyzed. The mean and
      SD of the distance were less than 0.80 and 0.52 mm, respectively. The maximum
      ranges of tumor motion on cine-MRI were 2.4 +/- 1.4 mm (range, 1.0-5.0 mm), 4.4
      +/- 3.3 mm (range, 0.8-9.4 mm), and 14.7 +/- 5.9 mm (range, 7.4-23.4 mm) in
      lateral, anterior-posterior, and superior-inferior directions, respectively. The
      ranges in the superior-inferior direction were larger than those estimated with
      4DCT images for all patients. The volume of ITV Potential was 160.3% +/- 13.5%
      (range, 142.0%-179.2%) of the ITV 4DCT. The maximum DSC values were observed when
      the cutoff value of 24.7% +/- 4.0% (range, 20%-29%) was applied. CONCLUSIONS: The
      authors demonstrated a novel method of calculating 3D motion and ITV Potential of
      liver cancer using orthogonal cine-MRI. Their method achieved accurate
      calculation of the respiratory motion of moving structures. Individual evaluation
      of the ITV Potential will aid in improving respiration management and treatment
      planning.

PMID- 25370620
TI  - Confirmation of a realistic reactor model for BNCT dosimetry at the TRIGA Mainz.
AB  - PURPOSE: In order to build up a reliable dose monitoring system for boron neutron
      capture therapy (BNCT) applications at the TRIGA reactor in Mainz, a computer
      model for the entire reactor was established, simulating the radiation field by
      means of the Monte Carlo method. The impact of different source definition
      techniques was compared and the model was validated by experimental fluence and
      dose determinations. METHODS: The depletion calculation code origen2 was used to
      compute the burn-up and relevant material composition of each burned fuel element
      from the day of first reactor operation to its current core. The material
      composition of the current core was used in a mcnp5 model of the initial core
      developed earlier. To perform calculations for the region outside the reactor
      core, the model was expanded to include the thermal column and compared with the
      previously established attila model. Subsequently, the computational model is
      simplified in order to reduce the calculation time. Both simulation models are
      validated by experiments with different setups using alanine dosimetry and gold
      activation measurements with two different types of phantoms. RESULTS: The mcnp5
      simulated neutron spectrum and source strength are found to be in good agreement
      with the previous attila model whereas the photon production is much lower. Both
      mcnp5 simulation models predict all experimental dose values with an accuracy of
      about 5%. The simulations reveal that a Teflon environment favorably reduces the
      gamma dose component as compared to a polymethyl methacrylate phantom.
      CONCLUSIONS: A computer model for BNCT dosimetry was established, allowing the
      prediction of dosimetric quantities without further calibration and within a
      reasonable computation time for clinical applications. The good agreement between
      the mcnp5 simulations and experiments demonstrates that the attila model
      overestimates the gamma dose contribution. The detailed model can be used for the
      planning of structural modifications in the thermal column irradiation channel or
      the use of different irradiation sites than the thermal column, e.g., the beam
      tubes.

PMID- 25370619
TI  - Multiple anatomy optimization of accumulated dose.
AB  - PURPOSE: To investigate the potential advantages of multiple anatomy optimization
      (MAO) for lung cancer radiation therapy compared to the internal target volume
      (ITV) approach. METHODS: MAO aims to optimize a single fluence to be delivered
      under free-breathing conditions such that the accumulated dose meets the plan
      objectives, where accumulated dose is defined as the sum of deformably mapped
      doses computed on each phase of a single four dimensional computed tomography
      (4DCT) dataset. Phantom and patient simulation studies were carried out to
      investigate potential advantages of MAO compared to ITV planning. Through
      simulated delivery of the ITV- and MAO-plans, target dose variations were also
      investigated. RESULTS: By optimizing the accumulated dose, MAO shows the
      potential to ensure dose to the moving target meets plan objectives while
      simultaneously reducing dose to organs at risk (OARs) compared with ITV planning.
      While consistently superior to the ITV approach, MAO resulted in equivalent OAR
      dosimetry at planning objective dose levels to within 2% volume in 14/30 plans
      and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and
      heart V30. Despite large variations in per-fraction respiratory phase weights in
      simulated deliveries at high dose rates (e.g., treating 4/10 phases during single
      fraction beams) the cumulative clinical target volume (CTV) dose after 30
      fractions and per-fraction dose were constant independent of planning technique.
      In one case considered, however, per-phase CTV dose varied from 74% to 117% of
      prescription implying the level of ITV-dose heterogeneity may not be appropriate
      with conventional, free-breathing delivery. CONCLUSIONS: MAO incorporates 4DCT
      information in an optimized dose distribution and can achieve a superior plan in
      terms of accumulated dose to the moving target and OAR sparing compared to ITV
      plans. An appropriate level of dose heterogeneity in MAO plans must be further
      investigated.

PMID- 25370621
TI  - Monte Carlo study of the depth-dependent fluence perturbation in parallel-plate
      ionization chambers in electron beams.
AB  - PURPOSE: The electron fluence inside a parallel-plate ionization chamber
      positioned in a water phantom and exposed to a clinical electron beam deviates
      from the unperturbed fluence in water in absence of the chamber. One reason for
      the fluence perturbation is the well-known "inscattering effect," whose physical
      cause is the lack of electron scattering in the gas-filled cavity. Correction
      factors determined to correct for this effect have long been recommended.
      However, more recent Monte Carlo calculations have led to some doubt about the
      range of validity of these corrections. Therefore, the aim of the present study
      is to reanalyze the development of the fluence perturbation with depth and to
      review the function of the guard rings. METHODS: Spatially resolved Monte Carlo
      simulations of the dose profiles within gas-filled cavities with various radii in
      clinical electron beams have been performed in order to determine the radial
      variation of the fluence perturbation in a coin-shaped cavity, to study the
      influences of the radius of the collecting electrode and of the width of the
      guard ring upon the indicated value of the ionization chamber formed by the
      cavity, and to investigate the development of the perturbation as a function of
      the depth in an electron-irradiated phantom. The simulations were performed for a
      primary electron energy of 6 MeV. RESULTS: The Monte Carlo simulations clearly
      demonstrated a surprisingly large in- and outward electron transport across the
      lateral cavity boundary. This results in a strong influence of the depth
      dependent development of the electron field in the surrounding medium upon the
      chamber reading. In the buildup region of the depth-dose curve, the in-out
      balance of the electron fluence is positive and shows the well-known dose
      oscillation near the cavity/water boundary. At the depth of the dose maximum the
      in-out balance is equilibrated, and in the falling part of the depth-dose curve
      it is negative, as shown here the first time. The influences of both the
      collecting electrode radius and the width of the guard ring are reflecting the
      deep radial penetration of the electron transport processes into the gas-filled
      cavities and the need for appropriate corrections of the chamber reading. New
      values for these corrections have been established in two forms, one converting
      the indicated value into the absorbed dose to water in the front plane of the
      chamber, the other converting it into the absorbed dose to water at the depth of
      the effective point of measurement of the chamber. In the Appendix, the in-out
      imbalance of electron transport across the lateral cavity boundary is
      demonstrated in the approximation of classical small-angle multiple scattering
      theory. CONCLUSIONS: The in-out electron transport imbalance at the lateral
      boundaries of parallel-plate chambers in electron beams has been studied with
      Monte Carlo simulation over a range of depth in water, and new correction
      factors, covering all depths and implementing the effective point of measurement
      concept, have been developed.

PMID- 25370622
TI  - Respiratory motion management using audio-visual biofeedback for respiratory
      gated radiotherapy of synchrotron-based pulsed heavy-ion beam delivery.
AB  - PURPOSE: To efficiently deliver respiratory-gated radiation during synchrotron
      based pulsed heavy-ion radiotherapy, a novel respiratory guidance method
      combining a personalized audio-visual biofeedback (BFB) system, breath hold (BH),
      and synchrotron-based gating was designed to help patients synchronize their
      respiratory patterns with synchrotron pulses and to overcome typical limitations
      such as low efficiency, residual motion, and discomfort. METHODS: In-house
      software was developed to acquire body surface marker positions and display BFB,
      gating signals, and real-time beam profiles on a LED screen. Patients were
      prompted to perform short BHs or short deep breath holds (SDBH) with the aid of
      BFB following a personalized standard BH/SDBH (stBH/stSDBH) guiding curve or
      their own representative BH/SDBH (reBH/reSDBH) guiding curve. A practical
      simulation was performed for a group of 15 volunteers to evaluate the feasibility
      and effectiveness of this method. Effective dose rates (EDRs), mean absolute
      errors between the guiding curves and the measured curves, and mean absolute
      deviations of the measured curves were obtained within 10%-50% duty cycles (DCs)
      that were synchronized with the synchrotron's flat-top phase. RESULTS: All
      maneuvers for an individual volunteer took approximately half an hour, and no one
      experienced discomfort during the maneuvers. Using the respiratory guidance
      methods, the magnitude of residual motion was almost ten times less than during
      nongated irradiation, and increases in the average effective dose rate by factors
      of 2.39-4.65, 2.39-4.59, 1.73-3.50, and 1.73-3.55 for the stBH, reBH, stSDBH, and
      reSDBH guiding maneuvers, respectively, were observed in contrast with
      conventional free breathing-based gated irradiation, depending on the respiratory
      gated duty cycle settings. CONCLUSIONS: The proposed respiratory guidance method
      with personalized BFB was confirmed to be feasible in a group of volunteers.
      Increased effective dose rate and improved overall treatment precision were
      observed compared to conventional free breathing-based, respiratory-gated
      irradiation. Because breathing guidance curves could be established based on the
      respective average respiratory period and amplitude for each patient, it may be
      easier for patients to cooperate using this technique.

PMID- 25370623
TI  - Asymmetric dose-volume optimization with smoothness control for rotating-shield
      brachytherapy.
AB  - PURPOSE: It is important to reduce fluence map complexity in rotating-shield
      brachytherapy (RSBT) inverse planning to improve delivery efficiency while
      maintaining plan quality. This study proposes an efficient and effective RSBT
      dose optimization method which enables to produce smooth fluence maps. METHODS:
      Five cervical cancer patients each with a high-risk clinical-target-volume (HR
      CTV) larger than 40 cm(3) were considered as the test cases. The RSBT source was
      a partially shielded electronic brachytherapy source (Xoft AxxentTM). The anchor
      RSBT plans generated by the asymmetric dose-volume optimization with smoothness
      control (ADOS) method were compared against those produced by the dose-surface
      optimization (DSO) method and inverse-planning with simulated annealing (IPSA).
      Either L1-norm or L2-norm was used to measure the smoothness of a fluence map in
      the proposed ADOS method as one weighted term of the objective function. Uniform
      dwell-time scaling was applied to all plans such that HR-CTV D90 was maximized
      without violating the D2cc tolerances of the rectum, bladder, and sigmoid colon.
      The quality of the anchor plans was measured with HR-CTV D90 of the anchor plans.
      Single-shielded RSBT [(S-RSBT), RSBT with single, fix sized delivery window] and
      dynamic-sheilded RSBT [(D-RSBT), RSBT with dynamically varying sized delivery
      window] delivery plans generated based on the anchor plans were also measured,
      with delivery time constraints of 10, 20, and 30 min/fraction (fx). RESULTS: The
      average HR-CTV D90 values of the anchor plans achieved by the ADOS, DSO, and IPSA
      methods were 111.5, 94.2, and 107.4 Gy, respectively, where the weighting
      parameter beta used in ADOS with L2-norm was set to be 100. By using S-RSBT
      sequencing and 20 min/fx delivery time, the corresponding D90 values were 88.8,
      81.9, and 83.4 Gy; while using D-RSBT sequencing with 20 min/fx delivery time,
      the corresponding D90 values were 91.4, 88.3, and 78.9 Gy, respectively. The
      average optimization times for ADOS, DSO, and IPSA were, respectively, 77, 4, and
      1800 s. By using L1-norm instead of L2-norm in the ADOS method, the optimization
      time was increased by 20 s, while the D90 was reduced by 6.8 Gy on average. ADOS
      L1 was found to be more sensitive to the weighting parameter than ADOS-L2. If
      beta was increased to 10 000, the D90 drop with ADOS-L1 was 38 Gy, while the drop
      with ADOS-L2 is 13 Gy. CONCLUSIONS: The ADOS method had a reasonable optimization
      time cost, while achieving comparable RSBT dose plans as the IPSA method, which
      is of much higher time complexity. Compared to the DSO and IPSA methods, ADOS is
      able to generate anchor plans which are more suitable for RSBT delivery while
      preserving the high quality of the original plans. Compared to ADOS-L1, ADOS-L2
      is able to achieve better quality of anchor plans more efficiently.

PMID- 25370624
TI  - Benchmarking of a treatment planning system for spot scanning proton therapy:
      comparison and analysis of robustness to setup errors of photon IMRT and proton
      SFUD treatment plans of base of skull meningioma.
AB  - PURPOSE: Base of skull meningioma can be treated with both intensity modulated
      radiation therapy (IMRT) and spot scanned proton therapy (PT). One of the main
      benefits of PT is better sparing of organs at risk, but due to the physical and
      dosimetric characteristics of protons, spot scanned PT can be more sensitive to
      the uncertainties encountered in the treatment process compared with photon
      treatment. Therefore, robustness analysis should be part of a comprehensive
      comparison between these two treatment methods in order to quantify and
      understand the sensitivity of the treatment techniques to uncertainties. The aim
      of this work was to benchmark a spot scanning treatment planning system for
      planning of base of skull meningioma and to compare the created plans and analyze
      their robustness to setup errors against the IMRT technique. METHODS: Plans were
      produced for three base of skull meningioma cases: IMRT planned with a commercial
      TPS [Monaco (Elekta AB, Sweden)]; single field uniform dose (SFUD) spot scanning
      PT produced with an in-house TPS (PSI-plan); and SFUD spot scanning PT plan
      created with a commercial TPS [XiO (Elekta AB, Sweden)]. A tool for evaluating
      robustness to random setup errors was created and, for each plan, both a
      dosimetric evaluation and a robustness analysis to setup errors were performed.
      RESULTS: It was possible to create clinically acceptable treatment plans for spot
      scanning proton therapy of meningioma with a commercially available TPS. However,
      since each treatment planning system uses different methods, this comparison
      showed different dosimetric results as well as different sensitivities to setup
      uncertainties. The results confirmed the necessity of an analysis tool for
      assessing plan robustness to provide a fair comparison of photon and proton
      plans. CONCLUSIONS: Robustness analysis is a critical part of plan evaluation
      when comparing IMRT plans with spot scanned proton therapy plans.

PMID- 25370625
TI  - Spatial variation of dosimetric leaf gap and its impact on dose delivery.
AB  - PURPOSE: During dose calculation, the Eclipse treatment planning system (TPS)
      retracts the multileaf collimator (MLC) leaf positions by half of the dosimetric
      leaf gap (DLG) value (measured at central axis) for all leaf positions in a
      dynamic MLC plan to accurately model the rounded leaf ends. The aim of this study
      is to map the variation of DLG along the travel path of each MLC leaf pair and
      quantify how this variation impacts delivered dose. METHODS: 6 MV DLG values were
      measured for all MLC leaf pairs in increments of 1.0 cm (from the line
      intersecting the CAX and perpendicular to MLC motion) to 13.0 cm off axis
      distance at dmax. The measurements were performed on two Varian linear
      accelerators, both employing the Millennium 120-leaf MLCs. The measurements were
      performed at several locations in the beam with both a Sun Nuclear MapCHECK
      device and a PTW pinpoint ion chamber. RESULTS: The measured DLGs for the middle
      40 MLC leaf pairs (each 0.5 cm width) at positions along a line through the CAX
      and perpendicular to MLC leaf travel direction were very similar, varying
      maximally by only 0.2 mm. The outer 20 MLC leaf pairs (each 1.0 cm width) have
      much lower DLG values, about 0.3-0.5 mm lower than the central MLC leaf pair, at
      their respective central line position. Overall, the mean and the maximum
      variation between the 0.5 cm width leaves and the 1.0 cm width leaf pairs are
      0.32 and 0.65 mm, respectively. CONCLUSIONS: The spatial variation in DLG is
      caused by the variation of intraleaf transmission through MLC leaves. Fluences
      centered on the CAX would not be affected since DLG does not vary; but any
      fluences residing significantly off axis with narrow sweeping leaves may exhibit
      significant dose differences. This is due to the fact that there are differences
      in DLG between the true DLG exhibited by the 1.0 cm width outer leaves and the
      constant DLG value utilized by the TPS for dose calculation. Since there are
      large differences in DLG between the 0.5 cm width leaf pairs and 1.0 cm width
      leaf pairs, there is a need to correct the TPS plans, especially those with high
      modulation (narrow dynamic MLC gap), with 2D variation of DLG.

PMID- 25370626
TI  - Quality assurance for the clinical implementation of kilovoltage intrafraction
      monitoring for prostate cancer VMAT.
AB  - PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a real-time 3D tumor
      monitoring system for cancer radiotherapy. KIM uses the commonly available gantry
      mounted x-ray imager as input, making this method potentially more widely
      available than dedicated real-time 3D tumor monitoring systems. KIM is being
      piloted in a clinical trial for prostate cancer patients treated with VMAT
      (NCT01742403). The purpose of this work was to develop clinical process and
      quality assurance (QA) practices for the clinical implementation of KIM. METHODS:
      Informed by and adapting existing guideline documents from other real-time
      monitoring systems, KIM-specific QA practices were developed. The following five
      KIM-specific QA tests were included: (1) static localization accuracy, (2)
      dynamic localization accuracy, (3) treatment interruption accuracy, (4) latency
      measurement, and (5) clinical conditions accuracy. Tests (1)-(4) were performed
      using KIM to measure static and representative patient-derived prostate motion
      trajectories using a 3D programmable motion stage supporting an anthropomorphic
      phantom with implanted gold markers to represent the clinical treatment scenario.
      The threshold for system tolerable latency is <1 s. The tolerances for all other
      tests are that both the mean and standard deviation of the difference between the
      programmed trajectory and the measured data are <1 mm. The (5) clinical
      conditions accuracy test compared the KIM measured positions with those measured
      by kV/megavoltage (MV) triangulation from five treatment fractions acquired in a
      previous pilot study. RESULTS: For the (1) static localization, (2) dynamic
      localization, and (3) treatment interruption accuracy tests, the mean and
      standard deviation of the difference are <1.0 mm. (4) The measured latency is 350
      ms. (5) For the tests with previously acquired patient data, the mean and
      standard deviation of the difference between KIM and kV/MV triangulation are <1.0
      mm. CONCLUSIONS: Clinical process and QA practices for the safe clinical
      implementation of KIM, a novel real-time monitoring system using commonly
      available equipment, have been developed and implemented for prostate cancer
      VMAT.

PMID- 25370627
TI  - Dosimetric feasibility of real-time MRI-guided proton therapy.
AB  - PURPOSE: Magnetic resonance imaging (MRI) is a prime candidate for image-guided
      radiotherapy. This study was designed to assess the feasibility of real-time MRI
      guided proton therapy by quantifying the dosimetric effects induced by the
      magnetic field in patients' plans and identifying the associated clinical
      consequences. METHODS: Monte Carlo dose calculation was performed for nine
      patients of various treatment sites (lung, liver, prostate, brain, skull-base,
      and spine) and tissue homogeneities, in the presence of 0.5 and 1.5 T magnetic
      fields. Dose volume histogram (DVH) parameters such as D95, D5, and V20 as well
      as equivalent uniform dose were compared for the target and organs at risk,
      before and after applying the magnetic field. The authors further assessed
      whether the plans affected by clinically relevant dose distortions could be
      corrected independent of the planning system. RESULTS: By comparing the resulting
      dose distributions and analyzing the respective DVHs, it was determined that
      despite the observed lateral beam deflection, for magnetic fields of up to 0.5 T,
      neither was the target coverage jeopardized nor was the dose to the nearby organs
      increased in all cases except for prostate. However, for a 1.5 T magnetic field,
      the dose distortions were more pronounced and of clinical concern in all cases
      except for spine. In such circumstances, the target was severely underdosed, as
      indicated by a decrease in D95 of up to 41% of the prescribed dose compared to
      the nominal situation (no magnetic field). Sites such as liver and spine were
      less affected due to higher tissue homogeneity, typically smaller beam range, and
      the choice of beam directions. Simulations revealed that small modifications to
      certain plan parameters such as beam isocenter (up to 19 mm) and gantry angle (up
      to 10 degrees ) are sufficient to compensate for the magnetic field-induced dose
      disturbances. The authors' observations indicate that the degree of required
      corrections strongly depends on the beam range and direction relative to the
      magnetic field. This method was also applicable to more heterogeneous scenarios
      such as skull-base tumors. CONCLUSIONS: This study confirmed the dosimetric
      feasibility of real-time MRI-guided proton therapy and delivering a clinically
      acceptable dose to patients with various tumor locations within magnetic fields
      of up to 1.5 T. This work could serve as a guide and encouragement for further
      efforts toward clinical implementation of hybrid MRI-proton gantry systems.

PMID- 25370628
TI  - Sensitivity study of voxel-based PET image comparison to image registration
      algorithms.
AB  - PURPOSE: Accurate deformable registration is essential for voxel-based comparison
      of sequential positron emission tomography (PET) images for proper adaptation of
      treatment plan and treatment response assessment. The comparison may be sensitive
      to the method of deformable registration as the optimal algorithm is unknown.
      This study investigated the impact of registration algorithm choice on therapy
      response evaluation. METHODS: Sixteen patients with 20 lung tumors underwent a
      pre- and post-treatment computed tomography (CT) and 4D FDG-PET scans before and
      after chemoradiotherapy. All CT images were coregistered using a rigid and ten
      deformable registration algorithms. The resulting transformations were then
      applied to the respective PET images. Moreover, the tumor region defined by a
      physician on the registered PET images was classified into progressor, stable
      disease, and responder subvolumes. Particularly, voxels with standardized uptake
      value (SUV) decreases >30% were classified as responder, while voxels with SUV
      increases >30% were progressor. All other voxels were considered stable-disease.
      The agreement of the subvolumes resulting from difference registration algorithms
      was assessed by Dice similarity index (DSI). Coefficient of variation (CV) was
      computed to assess variability of DSI between individual tumors. Root mean square
      difference (RMSrigid) of the rigidly registered CT images was used to measure the
      degree of tumor deformation. RMSrigid and DSI were correlated by Spearman
      correlation coefficient (R) to investigate the effect of tumor deformation on
      DSI. RESULTS: Median DSIrigid was found to be 72%, 66%, and 80%, for progressor,
      stable-disease, and responder, respectively. Median DSIdeformable was 63%-84%,
      65%-81%, and 82%-89%. Variability of DSI was substantial and similar for both
      rigid and deformable algorithms with CV > 10% for all subvolumes. Tumor
      deformation had moderate to significant impact on DSI for progressor subvolume
      with Rrigid = - 0.60 (p = 0.01) and Rdeformable = - 0.46 (p = 0.01-0.20)
      averaging over all deformable algorithms. For stable-disease subvolumes, the
      correlations were significant (p < 0.001) for all registration algorithms with
      Rrigid = - 0.71 and Rdeformable = - 0.72. Progressor and stable-disease
      subvolumes resulting from rigid registration were in excellent agreement (DSI >
      70%) for RMSrigid < 150 HU. However, tumor deformation was observed to have
      negligible effect on DSI for responder subvolumes with insignificant |R| < 0.26,
      p > 0.27. CONCLUSIONS: This study demonstrated that deformable algorithms cannot
      be arbitrarily chosen; different deformable algorithms can result in large
      differences of voxel-based PET image comparison. For low tumor deformation
      (RMSrigid < 150 HU), rigid and deformable algorithms yield similar results,
      suggesting deformable registration is not required for these cases.

PMID- 25370629
TI  - Interactive prostate segmentation using atlas-guided semi-supervised learning and
      adaptive feature selection.
AB  - PURPOSE: Accurate prostate segmentation is necessary for maximizing the
      effectiveness of radiation therapy of prostate cancer. However, manual
      segmentation from 3D CT images is very time-consuming and often causes large
      intra- and interobserver variations across clinicians. Many segmentation methods
      have been proposed to automate this labor-intensive process, but tedious manual
      editing is still required due to the limited performance. In this paper, the
      authors propose a new interactive segmentation method that can (1) flexibly
      generate the editing result with a few scribbles or dots provided by a clinician,
      (2) fast deliver intermediate results to the clinician, and (3) sequentially
      correct the segmentations from any type of automatic or interactive segmentation
      methods. METHODS: The authors formulate the editing problem as a semisupervised
      learning problem which can utilize a priori knowledge of training data and also
      the valuable information from user interactions. Specifically, from a region of
      interest near the given user interactions, the appropriate training labels, which
      are well matched with the user interactions, can be locally searched from a
      training set. With voting from the selected training labels, both confident
      prostate and background voxels, as well as unconfident voxels can be estimated.
      To reflect informative relationship between voxels, location-adaptive features
      are selected from the confident voxels by using regression forest and Fisher
      separation criterion. Then, the manifold configuration computed in the derived
      feature space is enforced into the semisupervised learning algorithm. The labels
      of unconfident voxels are then predicted by regularizing semisupervised learning
      algorithm. RESULTS: The proposed interactive segmentation method was applied to
      correct automatic segmentation results of 30 challenging CT images. The
      correction was conducted three times with different user interactions performed
      at different time periods, in order to evaluate both the efficiency and the
      robustness. The automatic segmentation results with the original average Dice
      similarity coefficient of 0.78 were improved to 0.865-0.872 after conducting 55
      59 interactions by using the proposed method, where each editing procedure took
      less than 3 s. In addition, the proposed method obtained the most consistent
      editing results with respect to different user interactions, compared to other
      methods. CONCLUSIONS: The proposed method obtains robust editing results with few
      interactions for various wrong segmentation cases, by selecting the location
      adaptive features and further imposing the manifold regularization. The authors
      expect the proposed method to largely reduce the laborious burdens of manual
      editing, as well as both the intra- and interobserver variability across
      clinicians.

PMID- 25370630
TI  - Combining tissue-phantom ratios to provide a beam-quality specifier for
      flattening filter free photon beams.
AB  - PURPOSE: There are currently several commercially available radiotherapy
      treatment units without a flattening filter in the beam line. Unflattened photon
      beams have an energy and lateral fluence distribution that is different from
      conventional beams and, thus, their attenuation properties differ. As a
      consequence, for flattening filter free (FFF) beams, the relationship between the
      beam-quality specifier TPR20,10 and the Spencer-Attix restricted water-to-air
      mass collision stopping-power ratios, L/rhoair (water), may have to be refined in
      order to be used with equivalent accuracy as for beams with a flattening filter.
      The purpose of this work was twofold. First, to study the relationship between
      TPR20,10 and L/rhoair (water) for FFF beams, where the flattening filter has been
      replaced by a metal plate as in most clinical FFF beams. Second, to investigate
      the potential of increasing the accuracy in determining L/rhoair (water) by
      adding another beam-quality metric, TPR10,5. The relationship between L/rhoair
      (water) and %dd(10)x for beams with and without a flattening filter was also
      included in this study. METHODS: A total of 24 realistic photon beams (10 with
      and 14 without a flattening filter) from three different treatment units have
      been used to calculate L/rhoair (water), TPR20,10, and TPR10,5 using the EGSnrc
      Monte Carlo package. The relationship between L/rhoair (water) and the dual beam
      quality specifier TPR20,10 and TPR10,5 was described by a simple bilinear
      equation. The relationship between the photon beam-quality specifier %dd(10)x
      used in the AAPM's TG-51 dosimetry protocol and L/rhoair (water) was also
      investigated for the beams used in this study, by calculating the photon
      component of the percentage depth dose at 10 cm depth with SSD 100 cm. RESULTS:
      The calculated L/rhoair (water) for beams without a flattening filter was 0.3%
      lower, on average, than for beams with a flattening filter and comparable
      TPR20,10. Using the relationship in IAEA, TRS-398 resulted in a root mean square
      deviation (RMSD) of 0.0028 with a maximum deviation of 0.0043 (0.39%) from Monte
      Carlo calculated values. For all beams in this study, the RMSD between the
      proposed model and the Monte Carlo calculated values was 0.0006 with a maximum
      deviation of 0.0013 (0.1%). Using an earlier proposed relationship [Xiong and
      Rogers, Med. Phys. 35, 2104-2109 (2008)] between %dd(10)x and L/rhoair (water)
      gave a RMSD of 0.0018 with a maximum deviation of 0.0029 (0.26%) for all beams in
      this study (compared to RMSD 0.0015 and a maximum deviation of 0.0048 (0.47%) for
      the relationship used in AAPM TG-51 published by Almond et al. [Med. Phys. 26,
      1847-1870 (1999)]). CONCLUSIONS: Using TPR20,10 as a beam-quality specifier, for
      the flattening filter free beams used in this study, gave a maximum difference of
      0.39% between L/rhoair (water) predicted using IAEA TRS-398 and Monte Carlo
      calculations. An additional parameter for determining L/rhoair (water) has been
      presented. This parameter is easy to measure; it requires only an additional dose
      measurement at 5 cm depth with SSD 95 cm, and provides information for accurate
      determination of the L/rhoair (water) ratio for beams both with and without a
      flattening filter at the investigated energies.

PMID- 25370631
TI  - Rapid estimation of 4DCT motion-artifact severity based on 1D breathing-surrogate
      periodicity.
AB  - PURPOSE: Motion artifacts are common in patient four-dimensional computed
      tomography (4DCT) images, leading to an ill-defined tumor volume with large
      variations for radiotherapy treatment and a poor foundation with low imaging
      fidelity for studying respiratory motion. The authors developed a method to
      estimate 4DCT image quality by establishing a correlation between the severity of
      motion artifacts in 4DCT images and the periodicity of the corresponding 1D
      respiratory waveform (1DRW) used for phase binning in 4DCT reconstruction.
      METHODS: Discrete Fourier transformation (DFT) was applied to analyze 1DRW
      periodicity. The breathing periodicity index (BPI) was defined as the sum of the
      largest five Fourier coefficients, ranging from 0 to 1. Distortional motion
      artifacts (excluding blurring) of cine-scan 4DCT at the junctions of adjacent
      couch positions around the diaphragm were classified in three categories:
      incomplete, overlapping, and duplicate anatomies. To quantify these artifacts,
      discontinuity of the diaphragm at the junctions was measured in distance and
      averaged along six directions in three orthogonal views. Artifacts per junction
      (APJ) across the entire diaphragm were calculated in each breathing phase and
      phase-averaged APJ-, defined as motion-artifact severity (MAS), was obtained for
      each patient. To make MAS independent of patient-specific motion amplitude, two
      new MAS quantities were defined: MAS(D) is normalized to the maximum
      diaphragmatic displacement and MAS(V) is normalized to the mean diaphragmatic
      velocity (the breathing period was obtained from DFT analysis of 1DRW). Twenty
      six patients' free-breathing 4DCT images and corresponding 1DRW data were
      studied. RESULTS: Higher APJ values were found around midventilation and full
      inhalation while the lowest APJ values were around full exhalation. The
      distribution of MAS is close to Poisson distribution with a mean of 2.2 mm. The
      BPI among the 26 patients was calculated with a value ranging from 0.25 to 0.93.
      The DFT calculation was within 3 s per 1DRW. Correlations were found between 1DRW
      periodicity and 4DCT artifact severity: -0.71 for MAS(D) and -0.73 for MAS(V). A
      BPI greater than 0.85 in a 1DRW suggests minimal motion artifacts in the
      corresponding 4DCT images. CONCLUSIONS: The breathing periodicity index and
      motion-artifact severity index are introduced to assess the relationship between
      1DRW and 4DCT. A correlation between 1DRW periodicity and 4DCT artifact severity
      has been established. The 1DRW periodicity provides a rapid means to estimate
      4DCT image quality. The rapid 1DRW analysis and the correlative relationship can
      be applied prospectively to identify irregular breathers as candidates for breath
      coaching prior to 4DCT scan and retrospectively to select high-quality 4DCT
      images for clinical motion-management research.

PMID- 25370632
TI  - Texture analysis on the fluence map to evaluate the degree of modulation for
      volumetric modulated arc therapy.
AB  - PURPOSE: Texture analysis on fluence maps was performed to evaluate the degree of
      modulation for volumetric modulated arc therapy (VMAT) plans. METHODS: A total of
      six textural features including angular second moment, inverse difference moment,
      contrast, variance, correlation, and entropy were calculated for fluence maps
      generated from 20 prostate and 20 head and neck VMAT plans. For each of the
      textural features, particular displacement distances (d) of 1, 5, and 10 were
      adopted. To investigate the deliverability of each VMAT plan, gamma passing rates
      of pretreatment quality assurance, and differences in modulating parameters such
      as multileaf collimator (MLC) positions, gantry angles, and monitor units at each
      control point between VMAT plans and dynamic log files registered by the Linac
      control system during delivery were acquired. Furthermore, differences between
      the original VMAT plan and the plan reconstructed from the dynamic log files were
      also investigated. To test the performance of the textural features as indicators
      for the modulation degree of VMAT plans, Spearman's rank correlation coefficients
      (rs) with the plan deliverability were calculated. For comparison purposes,
      conventional modulation indices for VMAT including the modulation complexity
      score for VMAT, leaf travel modulation complexity score, and modulation index
      supporting station parameter optimized radiation therapy (MISPORT) were
      calculated, and their correlations were analyzed in the same way. RESULTS: There
      was no particular textural feature which always showed superior correlations with
      every type of plan deliverability. Considering the results comprehensively,
      contrast (d = 1) and variance (d = 1) generally showed considerable correlations
      with every type of plan deliverability. These textural features always showed
      higher correlations to the plan deliverability than did the conventional
      modulation indices, except in the case of modulating parameter differences. The
      rs values of contrast to the global gamma passing rates with criteria of 2%/2 mm,
      2%/1 mm, and 1%/2 mm were 0.536, 0.473, and 0.718, respectively. The respective
      values for variance were 0.551, 0.481, and 0.688. In the case of local gamma
      passing rates, the rs values of contrast were 0.547, 0.578, and 0.620,
      respectively, and those of variance were 0.519, 0.527, and 0.569. All of the rs
      values in those cases were statistically significant (p < 0.003). In the cases of
      global and local gamma passing rates, MISPORT showed the highest correlations
      among the conventional modulation indices. For global passing rates, rs values of
      MISPORT were -0.420, -0.330, and -0.632, respectively, and those for local
      passing rates were -0.455, -0.490 and -0.502. The values of rs of contrast,
      variance, and MISPORT with the MLC errors were -0.863, -0.828, and 0.795,
      respectively, all with statistical significances (p < 0.001). The correlations
      with statistical significances between variance and dose-volumetric differences
      were observed more frequently than the others. CONCLUSIONS: The contrast (d = 1)
      and variance (d = 1) calculated from fluence maps of VMAT plans showed
      considerable correlations with the plan deliverability, indicating their
      potential use as indicators for assessing the degree of modulation of VMAT plans.
      Both contrast and variance consistently showed better performance than the
      conventional modulation indices for VMAT.

PMID- 25370633
TI  - Dynamic tumor tracking using the Elekta Agility MLC.
AB  - PURPOSE: To evaluate the performance of the Elekta Agility multileaf collimator
      (MLC) for dynamic real-time tumor tracking. METHODS: The authors have developed a
      new control software which interfaces to the Agility MLC to dynamically program
      the movement of individual leaves, the dynamic leaf guides (DLGs), and the Y
      collimators ("jaws") based on the actual target trajectory. A motion platform was
      used to perform dynamic tracking experiments with sinusoidal trajectories. The
      actual target positions reported by the motion platform at 20, 30, or 40 Hz were
      used as shift vectors for the MLC in beams-eye-view. The system latency of the
      MLC (i.e., the average latency comprising target device reporting latencies and
      MLC adjustment latency) and the geometric tracking accuracy were extracted from a
      sequence of MV portal images acquired during irradiation for the following
      treatment scenarios: leaf-only motion, jaw + leaf motion, and DLG + leaf motion.
      RESULTS: The portal imager measurements indicated a clear dependence of the
      system latency on the target position reporting frequency. Deducting the effect
      of the target frequency, the leaf adjustment latency was measured to be 38 +/- 3
      ms for a maximum target speed v of 13 mm/s. The jaw + leaf adjustment latency was
      53 +/- 3 at a similar speed. The system latency at a target position frequency of
      30 Hz was in the range of 56-61 ms for the leaves (v <= 31 mm/s), 71-78 ms for
      the jaw + leaf motion (v <= 25 mm/s), and 58-72 ms for the DLG + leaf motion (v
      <= 59 mm/s). The tracking accuracy showed a similar dependency on the target
      position frequency and the maximum target speed. For the leaves, the root-mean
      squared error (RMSE) was between 0.6-1.5 mm depending on the maximum target
      speed. For the jaw + leaf (DLG + leaf) motion, the RMSE was between 0.7-1.5 mm
      (1.9-3.4 mm). CONCLUSIONS: The authors have measured the latency and geometric
      accuracy of the Agility MLC, facilitating its future use for clinical tracking
      applications.

PMID- 25370634
TI  - Physics-based shape matching for intraoperative image guidance.
AB  - PURPOSE: Soft-tissue deformations can severely degrade the validity of
      preoperative planning data during computer assisted interventions. Intraoperative
      imaging such as stereo endoscopic, time-of-flight or, laser range scanner data
      can be used to compensate these movements. In this context, the intraoperative
      surface has to be matched to the preoperative model. The shape matching is
      especially challenging in the intraoperative setting due to noisy sensor data,
      only partially visible surfaces, ambiguous shape descriptors, and real-time
      requirements. METHODS: A novel physics-based shape matching (PBSM) approach to
      register intraoperatively acquired surface meshes to preoperative planning data
      is proposed. The key idea of the method is to describe the nonrigid registration
      process as an electrostatic-elastic problem, where an elastic body (preoperative
      model) that is electrically charged slides into an oppositely charged rigid shape
      (intraoperative surface). It is shown that the corresponding energy functional
      can be efficiently solved using the finite element (FE) method. It is also
      demonstrated how PBSM can be combined with rigid registration schemes for robust
      nonrigid registration of arbitrarily aligned surfaces. Furthermore, it is shown
      how the approach can be combined with landmark based methods and outline its
      application to image guidance in laparoscopic interventions. RESULTS: A profound
      analysis of the PBSM scheme based on in silico and phantom data is presented.
      Simulation studies on several liver models show that the approach is robust to
      the initial rigid registration and to parameter variations. The studies also
      reveal that the method achieves submillimeter registration accuracy (mean error
      between 0.32 and 0.46 mm). An unoptimized, single core implementation of the
      approach achieves near real-time performance (2 TPS, 7-19 s total registration
      time). It outperforms established methods in terms of speed and accuracy.
      Furthermore, it is shown that the method is able to accurately match partial
      surfaces. Finally, a phantom experiment demonstrates how the method can be
      combined with stereo endoscopic imaging to provide nonrigid registration during
      laparoscopic interventions. CONCLUSIONS: The PBSM approach for surface matching
      is fast, robust, and accurate. As the technique is based on a preoperative
      volumetric FE model, it naturally recovers the position of volumetric structures
      (e.g., tumors and vessels). It cannot only be used to recover soft-tissue
      deformations from intraoperative surface models but can also be combined with
      landmark data from volumetric imaging. In addition to applications in
      laparoscopic surgery, the method might prove useful in other areas that require
      soft-tissue registration from sparse intraoperative sensor data (e.g., radiation
      therapy).

PMID- 25370635
TI  - Breast tumor segmentation in high resolution x-ray phase contrast analyzer based
      computed tomography.
AB  - PURPOSE: Phase contrast computed tomography has emerged as an imaging method,
      which is able to outperform present day clinical mammography in breast tumor
      visualization while maintaining an equivalent average dose. To this day, no
      segmentation technique takes into account the specificity of the phase contrast
      signal. In this study, the authors propose a new mathematical framework for human
      guided breast tumor segmentation. This method has been applied to high-resolution
      images of excised human organs, each of several gigabytes. METHODS: The authors
      present a segmentation procedure based on the viscous watershed transform and
      demonstrate the efficacy of this method on analyzer based phase contrast images.
      The segmentation of tumors inside two full human breasts is then shown as an
      example of this procedure's possible applications. RESULTS: A correct and precise
      identification of the tumor boundaries was obtained and confirmed by manual
      contouring performed independently by four experienced radiologists. CONCLUSIONS:
      The authors demonstrate that applying the watershed viscous transform allows them
      to perform the segmentation of tumors in high-resolution x-ray analyzer based
      phase contrast breast computed tomography images. Combining the additional
      information provided by the segmentation procedure with the already high
      definition of morphological details and tissue boundaries offered by phase
      contrast imaging techniques, will represent a valuable multistep procedure to be
      used in future medical diagnostic applications.

PMID- 25370636
TI  - Parallel-scanning tomosynthesis using a slot scanning technique: fixed-focus
      reconstruction and the resulting image quality.
AB  - PURPOSE: Parallel-scanning tomosynthesis (PS-TS) is a novel technique that fuses
      the slot scanning technique and the conventional tomosynthesis (TS) technique.
      This approach allows one to obtain long-view tomosynthesis images in addition to
      normally sized tomosynthesis images, even when using a system that has no linear
      tomographic scanning function. The reconstruction technique and an evaluation of
      the resulting image quality for PS-TS are described in this paper. METHODS: The
      PS-TS image-reconstruction technique consists of several steps (1) the projection
      images are divided into strips, (2) the strips are stitched together to construct
      images corresponding to the reconstruction plane, (3) the stitched images are
      filtered, and (4) the filtered stitched images are back-projected. In the case of
      PS-TS using the fixed-focus reconstruction method (PS-TS-F), one set of stitched
      images is used for the reconstruction planes at all heights, thus avoiding the
      necessity of repeating steps (1)-(3). A physical evaluation of the image quality
      of PS-TS-F compared with that of the conventional linear TS was performed using a
      R/F table (Sonialvision safire, Shimadzu Corp., Kyoto, Japan). The tomographic
      plane with the best theoretical spatial resolution (the in-focus plane, IFP) was
      set at a height of 100 mm from the table top by adjusting the reconstruction
      program. First, the spatial frequency response was evaluated at heights of -100, 
      50, 0, 50, 100, and 150 mm from the IFP using the edge of a 0.3-mm-thick copper
      plate. Second, the spatial resolution at each height was visually evaluated using
      an x-ray test pattern (Model No. 38, PTW Freiburg, Germany). Third, the slice
      sensitivity at each height was evaluated via the wire method using a 0.1-mm
      diameter tungsten wire. Phantom studies using a knee phantom and a whole-body
      phantom were also performed. RESULTS: The spatial frequency response of PS-TS-F
      yielded the best results at the IFP and degraded slightly as the distance from
      the IFP increased. A visual evaluation of the spatial resolution using the x-ray
      test pattern indicated that the resolution was 1.8 lp/mm at the IFP and 1.2 lp/mm
      at heights of -100 and 100 mm from the IFP. The authors demonstrated that a
      spatial resolution of 1.2-1.8 lp/mm could be obtained within heights of 200 mm of
      the IFP. The slice sensitivity varied between 11.1 and 13.8 mm for heights
      between -50 and 100 mm, and there was no critical change in the slice sensitivity
      within a height range of 150 mm around the IFP. The phantom results demonstrated
      that tomosynthesis and long-view images could be reconstructed. CONCLUSIONS: PS
      TS-F provides tomosynthesis images while using low-cost systems that have no
      tomographic scanning function, such as tableside-controlled universal R/F systems
      or universal radiographic systems.

PMID- 25370637
TI  - The effect of amorphous selenium detector thickness on dual-energy digital breast
      imaging.
AB  - PURPOSE: Contrast enhanced (CE) imaging techniques for both planar digital
      mammography (DM) and three-dimensional (3D) digital breast tomosynthesis (DBT)
      applications requires x-ray photon energies higher than the k-edge of iodine
      (33.2 keV). As a result, x-ray tube potentials much higher (>40 kVp) than those
      typical for screening mammography must be utilized. Amorphous selenium (a-Se)
      based direct conversion flat-panel imagers (FPI) have been widely used in DM and
      DBT imaging systems. The a-Se layer is typically 200 MUm thick with quantum
      detective efficiency (QDE) >87% for x-ray energies below 26 keV. However, QDE
      decreases substantially above this energy. To improve the object detectability of
      either CE-DM or CE-DBT, it may be advantageous to increase the thickness (dSe) of
      the a-Se layer. Increasing the dSe will improve the detective quantum efficiency
      (DQE) at the higher energies used in CE imaging. However, because most DBT
      systems are designed with partially isocentric geometries, where the gantry moves
      about a stationary detector, the oblique entry of x-rays will introduce
      additional blur to the system. The present investigation quantifies the effect of
      a-Se thickness on imaging performance for both CE-DM and CE-DBT, discussing the
      effects of improving photon absorption and blurring from oblique entry of x-rays.
      METHODS: In this paper, a cascaded linear system model (CLSM) was used to
      investigate the effect of dSe on the imaging performance (i.e., MTF, NPS, and
      DQE) of FPI in CE-DM and CE-DBT. The results from the model are used to calculate
      the ideal observer signal-to-noise ratio, d', which is used as a figure-of-merit
      to determine the total effect of increasing dSe for CE-DM and CE-DBT. RESULTS:
      The results of the CLSM show that increasing dSe causes a substantial increase in
      QDE at the high energies used in CE-DM. However, at the oblique projection angles
      used in DBT, the increased length of penetration through a-Se introduces
      additional image blur. The reduced MTF and DQE at high spatial frequencies lead
      to reduced two-dimensional d'. These losses in projection image resolution may
      subsequently result in a decrease in the 3D d', but the degree of which is
      largely dependent on the DBT reconstruction algorithm. For a filtered
      backprojection (FBP) algorithm with spectral apodization and slice-thickness
      filters, which dominate the blur for reconstructed images at oblique angles, the
      effect of oblique entry of x-rays on 3D d' is minimal. Thus, increasing dSe
      results in an improvement in d' for both CE-DM and CE-DBT with typical FBP
      reconstruction parameters. CONCLUSIONS: Increased dSe improves CE breast imaging
      performance by increasing QDE of detectors at higher energies, e.g., 49 kVp.
      Although there is additional blur in the oblique angled projections of a DBT
      scan, the overall 3D d' for DBT is not degraded because the dominant source blur
      at these angles results from the reconstruction filters of the employed FBP
      algorithm.

PMID- 25370638
TI  - Real-time out-of-plane artifact subtraction tomosynthesis imaging using prior CT
      for scanning beam digital x-ray system.
AB  - PURPOSE: The scanning beam digital x-ray system (SBDX) is an inverse geometry
      fluoroscopic system with high dose efficiency and the ability to perform
      continuous real-time tomosynthesis in multiple planes. This system could be used
      for image guidance during lung nodule biopsy. However, the reconstructed images
      suffer from strong out-of-plane artifact due to the small tomographic angle of
      the system. METHODS: The authors propose an out-of-plane artifact subtraction
      tomosynthesis (OPAST) algorithm that utilizes a prior CT volume to augment the
      run-time image processing. A blur-and-add (BAA) analytical model, derived from
      the project-to-backproject physical model, permits the generation of
      tomosynthesis images that are a good approximation to the shift-and-add (SAA)
      reconstructed image. A computationally practical algorithm is proposed to
      simulate images and out-of-plane artifacts from patient-specific prior CT volumes
      using the BAA model. A 3D image registration algorithm to align the simulated and
      reconstructed images is described. The accuracy of the BAA analytical model and
      the OPAST algorithm was evaluated using three lung cancer patients' CT data. The
      OPAST and image registration algorithms were also tested with added nonrigid
      respiratory motions. RESULTS: Image similarity measurements, including the
      correlation coefficient, mean squared error, and structural similarity index,
      indicated that the BAA model is very accurate in simulating the SAA images from
      the prior CT for the SBDX system. The shift-variant effect of the BAA model can
      be ignored when the shifts between SBDX images and CT volumes are within +/-10 mm
      in the x and y directions. The nodule visibility and depth resolution are
      improved by subtracting simulated artifacts from the reconstructions. The image
      registration and OPAST are robust in the presence of added respiratory motions.
      The dominant artifacts in the subtraction images are caused by the mismatches
      between the real object and the prior CT volume. CONCLUSIONS: Their proposed
      prior CT-augmented OPAST reconstruction algorithm improves lung nodule visibility
      and depth resolution for the SBDX system.

PMID- 25370639
TI  - Dose equations for shift-variant CT acquisition modes using variable pitch, tube
      current, and aperture, and the meaning of their associated CTDI(vol).
AB  - PURPOSE: With the increasing clinical use of shift-variant CT protocols involving
      tube current modulation (TCM), variable pitch or pitch modulation (PM), and
      variable aperture a(t), the interpretation of the scanner-reported CTDI(vol) is
      called into question. This was addressed for TCM in their previous paper
      published by Dixon and Boone [Med. Phys. 40, 111920 (14pp.) (2013)] and is
      extended to PM and concurrent TCM/PM as well as variable aperture in this work.
      METHODS: Rigorous convolution equations are derived to describe the accumulated
      dose distributions for TCM, PM, and concurrent TCM/PM. A comparison with scanner
      reported CTDI(vol) formulae clearly identifies the source of their differences
      with the traditional CTDI(vol). Dose distribution simulations using the
      convolution are provided for a variety of TCM and PM scenarios including a
      helical shuttle used for perfusion studies (as well as constant mA)-all having
      the same scanner-reported CTDI(vol). These new convolution simulations for TCM
      are validated by comparison with their previous discrete summations. RESULTS:
      These equations show that PM is equivalent to TCM if the pitch variation p(z) is
      proportional to 1/i(z), where i(z) is the local tube current. The simulations
      show that the local dose at z depends only weakly on the local tube current i(z)
      or local pitch p(z) due to scatter from all other locations along z, and that the
      "local CTDI(vol)(z)" or "CTDI(vol) per slice" do not represent a local dose but
      rather only a relative i(z) or p(z). The CTDI-paradigm does not apply to shift
      variant techniques and the scanner-reported CTDI(vol) for the same lacks physical
      significance and relevance. CONCLUSIONS: While the traditional CTDI(vol) at
      constant tube current and pitch conveys useful information (the peak dose at the
      center of the scan length), CTDI(vol) for shift-variant techniques (TCM or PM)
      conveys no useful information about the associated dose distribution it
      purportedly represents. On the other hand, the total energy absorbed E ("integral
      dose") as well as its surrogate DLP remain robust (invariant) with respect to
      shift-variance, depending only on the total mAs = <i>t0 accumulated during the
      total beam-on time t0 and aperture a, where <i> is the average current.

PMID- 25370640
TI  - Compartment modeling of dynamic brain PET--the impact of scatter corrections on
      parameter errors.
AB  - PURPOSE: The aim of this study was to investigate the effect of scatter and its
      correction on kinetic parameters in dynamic brain positron emission tomography
      (PET) tumor imaging. The 2-tissue compartment model was used, and two different
      reconstruction methods and two scatter correction (SC) schemes were investigated.
      METHODS: The gate Monte Carlo (MC) software was used to perform 2 * 15 full PET
      scan simulations of a voxelized head phantom with inserted tumor regions. The two
      sets of kinetic parameters of all tissues were chosen to represent the 2-tissue
      compartment model for the tracer 3'-deoxy-3'-((18)F)fluorothymidine (FLT), and
      were denoted FLT1 and FLT2. PET data were reconstructed with both 3D filtered
      back-projection with reprojection (3DRP) and 3D ordered-subset expectation
      maximization (OSEM). Images including true coincidences with attenuation
      correction (AC) and true+scattered coincidences with AC and with and without one
      of two applied SC schemes were reconstructed. Kinetic parameters were estimated
      by weighted nonlinear least squares fitting of image derived time-activity
      curves. Calculated parameters were compared to the true input to the MC
      simulations. RESULTS: The relative parameter biases for scatter-eliminated data
      were 15%, 16%, 4%, 30%, 9%, and 7% (FLT1) and 13%, 6%, 1%, 46%, 12%, and 8%
      (FLT2) for K1, k2, k3, k4, Va, and Ki, respectively. As expected, SC was
      essential for most parameters since omitting it increased biases by 10 percentage
      points on average. SC was not found necessary for the estimation of Ki and k3,
      however. There was no significant difference in parameter biases between the two
      investigated SC schemes or from parameter biases from scatter-eliminated PET
      data. Furthermore, neither 3DRP nor OSEM yielded the smallest parameter biases
      consistently although there was a slight favor for 3DRP which produced less
      biased k3 and Ki estimates while OSEM resulted in a less biased Va. The
      uncertainty in OSEM parameters was about 26% (FLT1) and 12% (FLT2) larger than
      for 3DRP although identical postfilters were applied. CONCLUSIONS: SC was
      important for good parameter estimations. Both investigated SC schemes performed
      equally well on average and properly corrected for the scattered radiation,
      without introducing further bias. Furthermore, 3DRP was slightly favorable over
      OSEM in terms of kinetic parameter biases and SDs.

PMID- 25370641
TI  - The image quality of ion computed tomography at clinical imaging dose levels.
AB  - PURPOSE: Accurately predicting the range of radiotherapy ions in vivo is
      important for the precise delivery of dose in particle therapy. Range uncertainty
      is currently the single largest contribution to the dose margins used in planning
      and leads to a higher dose to normal tissue. The use of ion CT has been proposed
      as a method to improve the range uncertainty and thereby reduce dose to normal
      tissue of the patient. A wide variety of ions have been proposed and studied for
      this purpose, but no studies evaluate the image quality obtained with different
      ions in a consistent manner. However, imaging doses ion CT is a concern which may
      limit the obtainable image quality. In addition, the imaging doses reported have
      not been directly comparable with x-ray CT doses due to the different biological
      impacts of ion radiation. The purpose of this work is to develop a robust
      methodology for comparing the image quality of ion CT with respect to particle
      therapy, taking into account different reconstruction methods and ion species.
      METHODS: A comparison of different ions and energies was made. Ion CT projections
      were simulated for five different scenarios: Protons at 230 and 330 MeV, helium
      ions at 230 MeV/u, and carbon ions at 430 MeV/u. Maps of the water equivalent
      stopping power were reconstructed using a weighted least squares method. The dose
      was evaluated via a quality factor weighted CT dose index called the CT dose
      equivalent index (CTDEI). Spatial resolution was measured by the modulation
      transfer function. This was done by a noise-robust fit to the edge spread
      function. Second, the image quality as a function of the number of scanning
      angles was evaluated for protons at 230 MeV. In the resolution study, the CTDEI
      was fixed to 10 mSv, similar to a typical x-ray CT scan. Finally, scans at a
      range of CTDEI's were done, to evaluate dose influence on reconstruction error.
      RESULTS: All ions yielded accurate stopping power estimates, none of which were
      statistically different from the ground truth image. Resolution (as defined by
      the modulation transfer function = 10% point) was the best for the helium ions
      (18.21 line pairs/cm) and worst for the lower energy protons (9.37 line
      pairs/cm). The weighted quality factor for the different ions ranged from 1.23
      for helium to 2.35 for carbon ions. For the angle study, a sharp increase in
      absolute error was observed below 45 distinct angles, giving the impression of a
      threshold, rather than smooth, limit to the number of angles. CONCLUSIONS: The
      method presented for comparing various ion CT modalities is feasible for
      practical use. While all studied ions would improve upon x-ray CT for particle
      range estimation, helium appears to give the best results and deserves further
      study for imaging.

PMID- 25370642
TI  - Signal to noise ratio of energy selective x-ray photon counting systems with
      pileup.
AB  - PURPOSE: To derive fundamental limits on the effect of pulse pileup and quantum
      noise in photon counting detectors on the signal to noise ratio (SNR) and noise
      variance of energy selective x-ray imaging systems. METHODS: An idealized model
      of the response of counting detectors to pulse pileup is used. The model assumes
      a nonparalyzable response and delta function pulse shape. The model is used to
      derive analytical formulas for the noise and energy spectrum of the recorded
      photons with pulse pileup. These formulas are first verified with a Monte Carlo
      simulation. They are then used with a method introduced in a previous paper [R.
      E. Alvarez, "Near optimal energy selective x-ray imaging system performance with
      simple detectors," Med. Phys. 37, 822-841 (2010)] to compare the signal to noise
      ratio with pileup to the ideal SNR with perfect energy resolution. Detectors
      studied include photon counting detectors with pulse height analysis (PHA),
      detectors that simultaneously measure the number of photons and the integrated
      energy (NQ detector), and conventional energy integrating and photon counting
      detectors. The increase in the A-vector variance with dead time is also computed
      and compared to the Monte Carlo results. A formula for the covariance of the NQ
      detector is developed. The validity of the constant covariance approximation to
      the Cramer-Rao lower bound (CRLB) for larger counts is tested. RESULTS: The SNR
      becomes smaller than the conventional energy integrating detector (Q) SNR for
      0.52, 0.65, and 0.78 expected number photons per dead time for counting (N), two,
      and four bin PHA detectors, respectively. The NQ detector SNR is always larger
      than the N and Q SNR but only marginally so for larger dead times. Its noise
      variance increases by a factor of approximately 3 and 5 for the A1 and A2
      components as the dead time parameter increases from 0 to 0.8 photons per dead
      time. With four bin PHA data, the increase in variance is approximately 2 and 4
      times. The constant covariance approximation to the CRLB is valid for larger
      counts such as those used in medical imaging. CONCLUSIONS: The SNR decreases
      rapidly as dead time increases. This decrease places stringent limits on
      allowable dead times with the high count rates required for medical imaging
      systems. The probability distribution of the idealized data with pileup is shown
      to be accurately described as a multivariate normal for expected counts greater
      than those typically utilized in medical imaging systems. The constant covariance
      approximation to the CRLB is also shown to be valid in this case. A new formula
      for the covariance of the NQ detector with pileup is derived and validated.

PMID- 25370643
TI  - Radiation dose calculations for CT scans with tube current modulation using the
      approach to equilibrium function.
AB  - PURPOSE: The approach to equilibrium function has been used previously to
      calculate the radiation dose to a shift-invariant medium undergoing CT scans with
      constant tube current [Li, Zhang, and Liu, Med. Phys. 39, 5347-5352 (2012)]. The
      authors have adapted this method to CT scans with tube current modulation (TCM).
      METHODS: For a scan with variable tube current, the scan range was divided into
      multiple subscan ranges, each with a nearly constant tube current. Then the dose
      calculation algorithm presented previously was applied. For a clinical CT scan
      series that presented tube current per slice, the authors adopted an efficient
      approach that computed the longitudinal dose distribution for one scan length
      equal to the slice thickness, which center was at z = 0. The cumulative dose at a
      specific point was a summation of the contributions from all slices and the
      overscan. RESULTS: The dose calculations performed for a total of four constant
      and variable tube current distributions agreed with the published results of
      Dixon and Boone [Med. Phys. 40, 111920 (14pp.) (2013)]. For an abdomen/pelvis
      scan of an anthropomorphic phantom (model ATOM 701-B, CIRS, Inc., VA) on a GE
      Lightspeed Pro 16 scanner with 120 kV, N * T = 20 mm, pitch = 1.375, z axis
      current modulation (auto mA), and angular current modulation (smart mA), dose
      measurements were performed using two lines of optically stimulated luminescence
      dosimeters, one of which was placed near the phantom center and the other on the
      surface. Dose calculations were performed on the central and peripheral axes of a
      cylinder containing water, whose cross-sectional mass was about equal to that of
      the ATOM phantom in its abdominal region, and the results agreed with the
      measurements within 28.4%. CONCLUSIONS: The described method provides an
      effective approach that takes into account subject size, scan length, and
      constant or variable tube current to evaluate CT dose to a shift-invariant
      medium. For a clinical CT scan, dose calculations may be performed with a water
      containing cylinder whose cross-sectional mass is equal to that of the subject.
      This method has the potential to substantially improve evaluations of patient
      dose from clinical CT scans, compared to CTDIvol, size-specific dose estimate
      (SSDE), or the dose evaluated for a TCM scan with a constant tube current equal
      to the average tube current of the TCM scan.

PMID- 25370644
TI  - CT reconstruction techniques for improved accuracy of lung CT airway measurement.
AB  - PURPOSE: To determine the impact of constrained reconstruction techniques on
      quantitative CT (qCT) of the lung parenchyma and airways for low x-ray radiation
      dose. METHODS: Measurement of small airways with qCT remains a challenge,
      especially for low x-ray dose protocols. Images of the COPDGene quality assurance
      phantom (CTP698, The Phantom Laboratory, Salem, NY) were obtained using a GE
      discovery CT750 HD scanner for helical scans at x-ray radiation dose-equivalents
      ranging from 1 to 4.12 mSv (12-100 mA s current-time product). Other parameters
      were 40 mm collimation, 0.984 pitch, 0.5 s rotation, and 0.625 mm thickness. The
      phantom was sandwiched between 7.5 cm thick water attenuating phantoms for a
      total length of 20 cm to better simulate the scatter conditions of patient scans.
      Image data sets were reconstructed using STANDARD (STD), DETAIL, BONE, and EDGE
      algorithms for filtered back projection (FBP), 100% adaptive statistical
      iterative reconstruction (ASIR), and Veo reconstructions. Reduced (half) display
      field of view (DFOV) was used to increase sampling across airway phantom
      structures. Inner diameter (ID), wall area percent (WA%), and wall thickness (WT)
      measurements of eight airway mimicking tubes in the phantom, including a 2.5 mm
      ID (42.6 WA%, 0.4 mm WT), 3 mm ID (49.0 WA%, 0.6 mm WT), and 6 mm ID (49.0 WA%,
      1.2 mm WT) were performed with Airway Inspector (Surgical Planning Laboratory,
      Brigham and Women's Hospital, Boston, MA) using the phase congruency edge
      detection method. The average of individual measures at five central slices of
      the phantom was taken to reduce measurement error. RESULTS: WA% measures were
      greatly overestimated while IDs were underestimated for the smaller airways,
      especially for reconstructions at full DFOV (36 cm) using the STD kernel, due to
      poor sampling and spatial resolution (0.7 mm pixel size). Despite low radiation
      dose, the ID of the 6 mm ID airway was consistently measured accurately for all
      methods other than STD FBP. Veo reconstructions showed slight improvement over
      STD FBP reconstructions (4%-9% increase in accuracy). The most improved ID and
      WA% measures were for the smaller airways, especially for low dose scans
      reconstructed at half DFOV (18 cm) with the EDGE algorithm in combination with
      100% ASIR to mitigate noise. Using the BONE + ASIR at half BONE technique,
      measures improved by a factor of 2 over STD FBP even at a quarter of the x-ray
      dose. CONCLUSIONS: The flexibility of ASIR in combination with higher frequency
      algorithms, such as BONE, provided the greatest accuracy for conventional and low
      x-ray dose relative to FBP. Veo provided more modest improvement in qCT measures,
      likely due to its compatibility only with the smoother STD kernel.

PMID- 25370646
TI  - High resolution Cerenkov light imaging of induced positron distribution in proton
      therapy.
AB  - PURPOSE: In proton therapy, imaging of the positron distribution produced by
      fragmentation during or soon after proton irradiation is a useful method to
      monitor the proton range. Although positron emission tomography (PET) is
      typically used for this imaging, its spatial resolution is limited. Cerenkov
      light imaging is a new molecular imaging technology that detects the visible
      photons that are produced from high-speed electrons using a high sensitivity
      optical camera. Because its inherent spatial resolution is much higher than PET,
      the authors can measure more precise information of the proton-induced positron
      distribution with Cerenkov light imaging technology. For this purpose, they
      conducted Cerenkov light imaging of induced positron distribution in proton
      therapy. METHODS: First, the authors evaluated the spatial resolution of our
      Cerenkov light imaging system with a (22)Na point source for the actual imaging
      setup. Then the transparent acrylic phantoms (100 * 100 * 100 mm(3)) were
      irradiated with two different proton energies using a spot scanning proton
      therapy system. Cerenkov light imaging of each phantom was conducted using a high
      sensitivity electron multiplied charge coupled device (EM-CCD) camera. RESULTS:
      The Cerenkov light's spatial resolution for the setup was 0.76 +/- 0.6 mm FWHM.
      They obtained high resolution Cerenkov light images of the positron distributions
      in the phantoms for two different proton energies and made fused images of the
      reference images and the Cerenkov light images. The depths of the positron
      distribution in the phantoms from the Cerenkov light images were almost identical
      to the simulation results. The decay curves derived from the region-of-interests
      (ROIs) set on the Cerenkov light images revealed that Cerenkov light images can
      be used for estimating the half-life of the radionuclide components of positrons.
      CONCLUSIONS: High resolution Cerenkov light imaging of proton-induced positron
      distribution was possible. The authors conclude that Cerenkov light imaging of
      proton-induced positron is promising for proton therapy.

PMID- 25370645
TI  - Towards the clinical implementation of iterative low-dose cone-beam CT
      reconstruction in image-guided radiation therapy: cone/ring artifact correction
      and multiple GPU implementation.
AB  - PURPOSE: Compressed sensing (CS)-based iterative reconstruction (IR) techniques
      are able to reconstruct cone-beam CT (CBCT) images from undersampled noisy data,
      allowing for imaging dose reduction. However, there are a few practical concerns
      preventing the clinical implementation of these techniques. On the image quality
      side, data truncation along the superior-inferior direction under the cone-beam
      geometry produces severe cone artifacts in the reconstructed images. Ring
      artifacts are also seen in the half-fan scan mode. On the reconstruction
      efficiency side, the long computation time hinders clinical use in image-guided
      radiation therapy (IGRT). METHODS: Image quality improvement methods are proposed
      to mitigate the cone and ring image artifacts in IR. The basic idea is to use
      weighting factors in the IR data fidelity term to improve projection data
      consistency with the reconstructed volume. In order to improve the computational
      efficiency, a multiple graphics processing units (GPUs)-based CS-IR system was
      developed. The parallelization scheme, detailed analyses of computation time at
      each step, their relationship with image resolution, and the acceleration factors
      were studied. The whole system was evaluated in various phantom and patient
      cases. RESULTS: Ring artifacts can be mitigated by properly designing a weighting
      factor as a function of the spatial location on the detector. As for the cone
      artifact, without applying a correction method, it contaminated 13 out of 80
      slices in a head-neck case (full-fan). Contamination was even more severe in a
      pelvis case under half-fan mode, where 36 out of 80 slices were affected, leading
      to poorer soft tissue delineation and reduced superior-inferior coverage. The
      proposed method effectively corrects those contaminated slices with mean
      intensity differences compared to FDK results decreasing from ~497 and ~293 HU to
      ~39 and ~27 HU for the full-fan and half-fan cases, respectively. In terms of
      efficiency boost, an overall 3.1 * speedup factor has been achieved with four GPU
      cards compared to a single GPU-based reconstruction. The total computation time
      is ~30 s for typical clinical cases. CONCLUSIONS: The authors have developed a
      low-dose CBCT IR system for IGRT. By incorporating data consistency-based
      weighting factors in the IR model, cone/ring artifacts can be mitigated. A boost
      in computational efficiency is achieved by multi-GPU implementation.

PMID- 25370647
TI  - Characterization of scatter in digital mammography from use of Monte Carlo
      simulations and comparison to physical measurements.
AB  - PURPOSE: Monte Carlo simulations were performed with the goal of verifying
      previously published physical measurements characterizing scatter as a function
      of apparent thickness. A secondary goal was to provide a way of determining what
      effect tissue glandularity might have on the scatter characteristics of breast
      tissue. The overall reason for characterizing mammography scatter in this
      research is the application of these data to an image processing-based scatter
      correction program. METHODS: mcnpx was used to simulate scatter from an
      infinitesimal pencil beam using typical mammography geometries and techniques.
      The spreading of the pencil beam was characterized by two parameters: mean radial
      extent (MRE) and scatter fraction (SF). The SF and MRE were found as functions of
      target, filter, tube potential, phantom thickness, and the presence or absence of
      a grid. The SF was determined by separating scatter and primary by the angle of
      incidence on the detector, then finding the ratio of the measured scatter to the
      total number of detected events. The accuracy of the MRE was determined by
      placing ring-shaped tallies around the impulse and fitting those data to the
      point-spread function (PSF) equation using the value for MRE derived from the
      physical measurements. The goodness-of-fit was determined for each data set as a
      means of assessing the accuracy of the physical MRE data. The effect of breast
      glandularity on the SF, MRE, and apparent tissue thickness was also considered
      for a limited number of techniques. RESULTS: The agreement between the physical
      measurements and the results of the Monte Carlo simulations was assessed. With a
      grid, the SFs ranged from 0.065 to 0.089, with absolute differences between the
      measured and simulated SFs averaging 0.02. Without a grid, the range was 0.28
      0.51, with absolute differences averaging -0.01. The goodness-of-fit values
      comparing the Monte Carlo data to the PSF from the physical measurements ranged
      from 0.96 to 1.00 with a grid and 0.65 to 0.86 without a grid. Analysis of the
      data suggested that the nongrid data could be better described by a biexponential
      function than the single exponential used here. The simulations assessing the
      effect of breast composition on SF and MRE showed only a slight impact on these
      quantities. When compared to a mix of 50% glandular/50% adipose tissue, the
      impact of substituting adipose or glandular breast compositions on the apparent
      thickness of the tissue was about 5%. CONCLUSIONS: The findings show agreement
      between the physical measurements published previously and the Monte Carlo
      simulations presented here; the resulting data can therefore be used more
      confidently for an application such as image processing-based scatter correction.
      The findings also suggest that breast composition does not have a major impact on
      the scatter characteristics of breast tissue. Application of the scatter data to
      the development of a scatter-correction software program can be simplified by
      ignoring the variations in density among breast tissues.

PMID- 25370649
TI  - Explicit solutions of the radiative transport equation in the P3 approximation.
AB  - PURPOSE: Explicit solutions of the monoenergetic radiative transport equation in
      the P3 approximation have been derived which can be evaluated with nearly the
      same computational effort as needed for solving the standard diffusion equation
      (DE). In detail, the authors considered the important case of a semi-infinite
      medium which is illuminated by a collimated beam of light. METHODS: A combination
      of the classic spherical harmonics method and the recently developed method of
      rotated reference frames is used for solving the P3 equations in closed form.
      RESULTS: The derived solutions are illustrated and compared to exact solutions of
      the radiative transport equation obtained via the Monte Carlo (MC) method as well
      as with other approximated analytical solutions. It is shown that for the
      considered cases which are relevant for biomedical optics applications, the P3
      approximation is close to the exact solution of the radiative transport equation.
      CONCLUSIONS: The authors derived exact analytical solutions of the P3 equations
      under consideration of boundary conditions for defining a semi-infinite medium.
      The good agreement to Monte Carlo simulations in the investigated domains, for
      example, in the steady-state and time domains, as well as the short evaluation
      time needed suggests that the derived equations can replace the often applied
      solutions of the diffusion equation for the homogeneous semi-infinite medium.

PMID- 25370648
TI  - Prostate CT segmentation method based on nonrigid registration in ultrasound
      guided CT-based HDR prostate brachytherapy.
AB  - PURPOSE: The technological advances in real-time ultrasound image guidance for
      high-dose-rate (HDR) prostate brachytherapy have placed this treatment modality
      at the forefront of innovation in cancer radiotherapy. Prostate HDR treatment
      often involves placing the HDR catheters (needles) into the prostate gland under
      the transrectal ultrasound (TRUS) guidance, then generating a radiation treatment
      plan based on CT prostate images, and subsequently delivering high dose of
      radiation through these catheters. The main challenge for this HDR procedure is
      to accurately segment the prostate volume in the CT images for the radiation
      treatment planning. In this study, the authors propose a novel approach that
      integrates the prostate volume from 3D TRUS images into the treatment planning CT
      images to provide an accurate prostate delineation for prostate HDR treatment.
      METHODS: The authors' approach requires acquisition of 3D TRUS prostate images in
      the operating room right after the HDR catheters are inserted, which takes 1-3
      min. These TRUS images are used to create prostate contours. The HDR catheters
      are reconstructed from the intraoperative TRUS and postoperative CT images, and
      subsequently used as landmarks for the TRUS-CT image fusion. After TRUS-CT
      fusion, the TRUS-based prostate volume is deformed to the CT images for treatment
      planning. This method was first validated with a prostate-phantom study. In
      addition, a pilot study of ten patients undergoing HDR prostate brachytherapy was
      conducted to test its clinical feasibility. The accuracy of their approach was
      assessed through the locations of three implanted fiducial (gold) markers, as
      well as T2-weighted MR prostate images of patients. RESULTS: For the phantom
      study, the target registration error (TRE) of gold-markers was 0.41 +/- 0.11 mm.
      For the ten patients, the TRE of gold markers was 1.18 +/- 0.26 mm; the prostate
      volume difference between the authors' approach and the MRI-based volume was
      7.28% +/- 0.86%, and the prostate volume Dice overlap coefficient was 91.89% +/-
      1.19%. CONCLUSIONS: The authors have developed a novel approach to improve
      prostate contour utilizing intraoperative TRUS-based prostate volume in the CT
      based prostate HDR treatment planning, demonstrated its clinical feasibility, and
      validated its accuracy with MRIs. The proposed segmentation method would improve
      prostate delineations, enable accurate dose planning and treatment delivery, and
      potentially enhance the treatment outcome of prostate HDR brachytherapy.

PMID- 25370650
TI  - Super-resolution reconstruction for 4D computed tomography of the lung via the
      projections onto convex sets approach.
AB  - PURPOSE: The use of 4D computed tomography (4D-CT) of the lung is important in
      lung cancer radiotherapy for tumor localization and treatment planning.
      Sometimes, dense sampling is not acquired along the superior-inferior direction.
      This disadvantage results in an interslice thickness that is much greater than in
      plane voxel resolutions. Isotropic resolution is necessary for multiplanar
      display, but the commonly used interpolation operation blurs images. This paper
      presents a super-resolution (SR) reconstruction method to enhance 4D-CT
      resolution. METHODS: The authors assume that the low-resolution images of
      different phases at the same position can be regarded as input "frames" to
      reconstruct high-resolution images. The SR technique is used to recover high
      resolution images. Specifically, the Demons deformable registration algorithm is
      used to estimate the motion field between different "frames." Then, the
      projection onto convex sets approach is implemented to reconstruct high
      resolution lung images. RESULTS: The performance of the SR algorithm is evaluated
      using both simulated and real datasets. Their method can generate clearer lung
      images and enhance image structure compared with cubic spline interpolation and
      back projection (BP) method. Quantitative analysis shows that the proposed
      algorithm decreases the root mean square error by 40.8% relative to cubic spline
      interpolation and 10.2% versus BP. CONCLUSIONS: A new algorithm has been
      developed to improve the resolution of 4D-CT. The algorithm outperforms the cubic
      spline interpolation and BP approaches by producing images with markedly improved
      structural clarity and greatly reduced artifacts.

PMID- 25370651
TI  - Automated characterization of perceptual quality of clinical chest radiographs:
      validation and calibration to observer preference.
AB  - PURPOSE: The authors previously proposed an image-based technique [Y. Lin et al.
      Med. Phys. 39, 7019-7031 (2012)] to assess the perceptual quality of clinical
      chest radiographs. In this study, an observer study was designed and conducted to
      validate the output of the program against rankings by expert radiologists and to
      establish the ranges of the output values that reflect the acceptable image
      appearance so the program output can be used for image quality optimization and
      tracking. METHODS: Using an IRB-approved protocol, 2500 clinical chest
      radiographs (PA/AP) were collected from our clinical operation. The images were
      processed through our perceptual quality assessment program to measure their
      appearance in terms of ten metrics of perceptual image quality: lung gray level,
      lung detail, lung noise, rib-lung contrast, rib sharpness, mediastinum detail,
      mediastinum noise, mediastinum alignment, subdiaphragm-lung contrast, and
      subdiaphragm area. From the results, for each targeted appearance
      attribute/metric, 18 images were selected such that the images presented a
      relatively constant appearance with respect to all metrics except the targeted
      one. The images were then incorporated into a graphical user interface, which
      displayed them into three panels of six in a random order. Using a DICOM
      calibrated diagnostic display workstation and under low ambient lighting
      conditions, each of five participating attending chest radiologists was tasked to
      spatially order the images based only on the targeted appearance attribute
      regardless of the other qualities. Once ordered, the observer also indicated the
      range of image appearances that he/she considered clinically acceptable. The
      observer data were analyzed in terms of the correlations between the observer and
      algorithmic rankings and interobserver variability. An observer-averaged
      acceptable image appearance was also statistically derived for each quality
      attribute based on the collected individual acceptable ranges. RESULTS: The
      observer study indicated that, for each image quality attribute, the averaged
      observer ranking strongly correlated with the algorithmic ranking (linear
      correlation coefficient R > 0.92), with highest correlation (R = 1) for lung gray
      level and the lowest (R = 0.92) for mediastinum noise. There was a strong
      concordance between the observers in terms of their rankings (i.e., Kendall's tau
      agreement > 0.84). The observers also generally indicated similar tolerance and
      preference levels in terms of acceptable ranges, as 85% of the values were close
      to the overall tolerance or preference levels and the differences were smaller
      than 0.15. CONCLUSIONS: The observer study indicates that the previously proposed
      technique provides a robust reflection of the perceptual image quality in
      clinical images. The results established the range of algorithmic outputs for
      each metric that can be used to quantitatively assess and qualify the appearance
      quality of clinical chest radiographs.

PMID- 25370652
TI  - Validation of a Monte Carlo model used for simulating tube current modulation in
      computed tomography over a wide range of phantom conditions/challenges.
AB  - PURPOSE: Monte Carlo (MC) simulation methods have been widely used in patient
      dosimetry in computed tomography (CT), including estimating patient organ doses.
      However, most simulation methods have undergone a limited set of validations,
      often using homogeneous phantoms with simple geometries. As clinical scanning has
      become more complex and the use of tube current modulation (TCM) has become
      pervasive in the clinic, MC simulations should include these techniques in their
      methodologies and therefore should also be validated using a variety of phantoms
      with different shapes and material compositions to result in a variety of
      differently modulated tube current profiles. The purpose of this work is to
      perform the measurements and simulations to validate a Monte Carlo model under a
      variety of test conditions where fixed tube current (FTC) and TCM were used.
      METHODS: A previously developed MC model for estimating dose from CT scans that
      models TCM, built using the platform of mcnpx, was used for CT dose
      quantification. In order to validate the suitability of this model to accurately
      simulate patient dose from FTC and TCM CT scan, measurements and simulations were
      compared over a wide range of conditions. Phantoms used for testing range from
      simple geometries with homogeneous composition (16 and 32 cm computed tomography
      dose index phantoms) to more complex phantoms including a rectangular homogeneous
      water equivalent phantom, an elliptical shaped phantom with three sections (where
      each section was a homogeneous, but different material), and a heterogeneous,
      complex geometry anthropomorphic phantom. Each phantom requires varying levels of
      x-, y- and z-modulation. Each phantom was scanned on a multidetector row CT
      (Sensation 64) scanner under the conditions of both FTC and TCM. Dose
      measurements were made at various surface and depth positions within each
      phantom. Simulations using each phantom were performed for FTC, detailed x-y-z
      TCM, and z-axis-only TCM to obtain dose estimates. This allowed direct
      comparisons between measured and simulated dose values under each condition of
      phantom, location, and scan to be made. RESULTS: For FTC scans, the percent root
      mean square (RMS) difference between measurements and simulations was within 5%
      across all phantoms. For TCM scans, the percent RMS of the difference between
      measured and simulated values when using detailed TCM and z-axis-only TCM
      simulations was 4.5% and 13.2%, respectively. For the anthropomorphic phantom,
      the difference between TCM measurements and detailed TCM and z-axis-only TCM
      simulations was 1.2% and 8.9%, respectively. For FTC measurements and
      simulations, the percent RMS of the difference was 5.0%. CONCLUSIONS: This work
      demonstrated that the Monte Carlo model developed provided good agreement between
      measured and simulated values under both simple and complex geometries including
      an anthropomorphic phantom. This work also showed the increased dose differences
      for z-axis-only TCM simulations, where considerable modulation in the x-y plane
      was present due to the shape of the rectangular water phantom. Results from this
      investigation highlight details that need to be included in Monte Carlo
      simulations of TCM CT scans in order to yield accurate, clinically viable
      assessments of patient dosimetry.

PMID- 25370653
TI  - Radiation-induced refraction artifacts in the optical CT readout of polymer gel
      dosimeters.
AB  - PURPOSE: The objective of this work is to demonstrate imaging artifacts that can
      occur during the optical computed tomography (CT) scanning of polymer gel
      dosimeters due to radiation-induced refractive index (RI) changes in
      polyacrylamide gels. METHODS: A 1 L cylindrical polyacrylamide gel dosimeter was
      irradiated with 3 * 3 cm(2) square beams of 6 MV photons. A prototype fan-beam
      optical CT scanner was used to image the dosimeter. Investigative optical CT
      scans were performed to examine two types of rayline bending: (i) bending within
      the plane of the fan-beam and (ii) bending out the plane of the fan-beam. To
      address structured errors, an iterative Savitzky-Golay (ISG) filtering routine
      was designed to filter 2D projections in sinogram space. For comparison, 2D
      projections were alternatively filtered using an adaptive-mean (AM) filter.
      RESULTS: In-plane rayline bending was most notably observed in optical CT
      projections where rays of the fan-beam confronted a sustained dose gradient that
      was perpendicular to their trajectory but within the fan-beam plane. These errors
      caused distinct streaking artifacts in image reconstructions due to the
      refraction of higher intensity rays toward more opaque regions of the dosimeter.
      Out-of-plane rayline bending was observed in slices of the dosimeter that
      featured dose gradients perpendicular to the plane of the fan-beam. These errors
      caused widespread, severe overestimations of dose in image reconstructions due to
      the higher-than-actual opacity that is perceived by the scanner when light is
      bent off of the detector array. The ISG filtering routine outperformed AM
      filtering for both in-plane and out-of-plane rayline errors caused by radiation
      induced RI changes. For in-plane rayline errors, streaks in an irradiated region
      (>7 Gy) were as high as 49% for unfiltered data, 14% for AM, and 6% for ISG. For
      out-of-plane rayline errors, overestimations of dose in a low-dose region (~50
      cGy) were as high as 13 Gy for unfiltered data, 10 Gy for AM, and 3.1 Gy for ISG.
      The ISG routine also addressed unrelated artifacts that previously needed to be
      manually removed in sinogram space. However, the ISG routine blurred
      reconstructions, causing losses in spatial resolution of ~5 mm in the plane of
      the fan-beam and ~8 mm perpendicular to the fan-beam. CONCLUSIONS: This paper
      reveals a new category of imaging artifacts that can affect the optical CT
      readout of polyacrylamide gel dosimeters. Investigative scans show that radiation
      induced RI changes can cause significant rayline errors when rays confront a
      prolonged dose gradient that runs perpendicular to their trajectory. In fan-beam
      optical CT, these errors manifested in two ways: (1) distinct streaking artifacts
      caused by in-plane rayline bending and (2) severe overestimations of opacity
      caused by rays bending out of the fan-beam plane and missing the detector array.
      Although the ISG filtering routine mitigated these errors better than an adaptive
      mean filtering routine, it caused unacceptable losses in spatial resolution.

PMID- 25370654
TI  - Technical note: Influence of the phantom material on the absorbed-dose energy
      dependence of the EBT3 radiochromic film for photons in the energy range 3 keV-18
      MeV.
AB  - PURPOSE: Water is the reference medium for radiation therapy dosimetry, but for
      film dosimetry it is more practical to use a solid phantom. As the composition of
      solid phantoms differs from that of water, the energy dependence of film exposed
      within solid phantoms may also differ. The energy dependence of a radiochromic
      film for a given beam quality Q (energy for monoenergetic beams) has two
      components: the intrinsic energy dependence and the absorbed-dose energy
      dependence f(Q), the latter of which can be calculated through a Monte Carlo
      simulation of radiation transport. The authors used Monte Carlo simulations to
      study the influence of the phantom material on the f(Q) of the EBT3 radiochromic
      film (Ashland Specialty Ingredients, Wayne, NJ) for photon beams with energies
      between 3 keV and 18 MeV. METHODS: All simulations were carried out with the
      general-purpose Monte Carlo code penelope 2011. The geometrical model consisted
      of a cylindrical phantom, with the film positioned at different depths depending
      on the initial photon energy. The authors simulated monoenergetic parallel photon
      beams and x-ray beams from a superficial therapy system. To validate their choice
      of simulation parameters, they also calculated f(Q) for older film models, EBT
      and EBT2, comparing with published results. In addition to water, they calculated
      f(Q) of the EBT3 film for solid phantom materials commonly used for film
      dosimetry: RW1 and RW3 (PTW-Freiburg, Freiburg, Germany), Solid Water (Gammex
      RMI, Madison, WI), and PMMA. Finally, they combined their calculated f(Q) with
      published overall energy response data to obtain the intrinsic energy dependence
      of the EBT3 film in water. RESULTS: The calculated f(Q) for EBT and EBT2 films
      was statistically compatible with previously published data. Between 10 keV and
      18 MeV, the variation found in f(Q) of the EBT3 film for water was within 2.3%,
      with a standard statistical uncertainty less than 1%. If the quantity dose-to
      water in the phantom is considered, which is the common practice in radiation
      dosimetry, the maximum difference of energy dependence for the solid phantoms
      with respect to water is about 6%, at an energy of 50 keV. CONCLUSIONS: The EBT3
      film shows a reasonably constant absorbed-dose energy dependence when irradiated
      in water. If the dose-to-water in the phantom is considered, the maximum
      difference of EBT3 film energy dependence with the solid phantoms studied with
      respect to water is about 6% (at an energy of 50 keV). The reported overall
      energy dependence of the EBT3 film in water at energies below 100 keV is mainly
      due to the intrinsic energy dependence.

PMID- 25370655
TI  - Application of a radiophotoluminescent glass dosimeter to nonreference condition
      dosimetry in the postal dose audit system.
AB  - PURPOSE: The purpose of this study was to obtain a set of correction factors of
      the radiophotoluminescent glass dosimeter (RGD) output for field size changes and
      wedge insertions. METHODS: Several linear accelerators were used for irradiation
      of the RGDs. The field sizes were changed from 5 * 5 cm to 25 * 25 cm for 4, 6,
      10, and 15 MV x-ray beams. The wedge angles were 15 degrees , 30 degrees , 45
      degrees , and 60 degrees . In addition to physical wedge irradiation, nonphysical
      (dynamic/virtual) wedge irradiations were performed. RESULTS: The obtained data
      were fitted with a single line for each energy, and correction factors were
      determined. Compared with ionization chamber outputs, the RGD outputs gradually
      increased with increasing field size, because of the higher RGD response to
      scattered low-energy photons. The output increase was about 1% per 10 cm increase
      in field size, with a slight difference dependent on the beam energy. For both
      physical and nonphysical wedged beam irradiation, there were no systematic trends
      in the RGD outputs, such as monotonic increase or decrease depending on the wedge
      angle change if the authors consider the uncertainty, which is approximately 0.6%
      for each set of measured points. Therefore, no correction factor was needed for
      all inserted wedges. Based on this work, postal dose audits using RGDs for the
      nonreference condition were initiated in 2010. The postal dose audit results
      between 2010 and 2012 were analyzed. The mean difference between the measured and
      stated doses was within 0.5% for all fields with field sizes between 5 * 5 cm and
      25 * 25 cm and with wedge angles from 15 degrees  to 60 degrees . The standard
      deviations (SDs) of the difference distribution were within the estimated
      uncertainty (1SD) except for the 25 * 25 cm field size data, which were not
      reliable because of poor statistics (n = 16). CONCLUSIONS: A set of RGD output
      correction factors was determined for field size changes and wedge insertions.
      The results obtained from recent postal dose audits were analyzed, and the mean
      differences between the measured and stated doses were within 0.5% for every
      field size and wedge angle. The SDs of the distribution were within the estimated
      uncertainty, except for one condition that was not reliable because of poor
      statistics.

PMID- 25370656
TI  - A new online detector for estimation of peripheral neutron equivalent dose in
      organ.
AB  - PURPOSE: Peripheral dose in radiotherapy treatments represents a potential source
      of secondary neoplasic processes. As in the last few years, there has been a fast
      growing concern on neutron collateral effects, this work focuses on this
      component. A previous established methodology to estimate peripheral neutron
      equivalent doses relied on passive (TLD, CR39) neutron detectors exposed in
      phantom, in parallel to an active [static random access memory (SRAMnd)] thermal
      neutron detector exposed ex-phantom. A newly miniaturized, quick, and reliable
      active thermal neutron detector (TNRD, Thermal Neutron Rate Detector) was
      validated for both procedures. This first miniaturized active system eliminates
      the long postprocessing, required for passive detectors, giving thermal neutron
      fluences in real time. METHODS: To validate TNRD for the established methodology,
      intrinsic characteristics, characterization of 4 facilities [to correlate monitor
      value (MU) with risk], and a cohort of 200 real patients (for second cancer risk
      estimates) were evaluated and compared with the well-established SRAMnd device.
      Finally, TNRD was compared to TLD pairs for 3 generic radiotherapy treatments
      through 16 strategic points inside an anthropomorphic phantom. RESULTS: The
      performed tests indicate similar linear dependence with dose for both detectors,
      TNRD and SRAMnd, while a slightly better reproducibility has been obtained for
      TNRD (1.7% vs 2.2%). Risk estimates when delivering 1000 MU are in good agreement
      between both detectors (mean deviation of TNRD measurements with respect to the
      ones of SRAMnd is 0.07 cases per 1000, with differences always smaller than 0.08
      cases per 1000). As far as the in-phantom measurements are concerned, a mean
      deviation smaller than 1.7% was obtained. CONCLUSIONS: The results obtained
      indicate that direct evaluation of equivalent dose estimation in organs, both in
      phantom and patients, is perfectly feasible with this new detector. This will
      open the door to an easy implementation of specific peripheral neutron dose
      models for any type of treatment and facility.

PMID- 25370657
TI  - T1-weighted MR image contrast around a cryoablation iceball: a phantom study and
      initial comparison with in vivo findings.
AB  - PURPOSE: To correlate T1-weighted (T1w) magnetic resonance (MR) image contrast
      around a cryoablation iceball with temperature in a phantom study and to compare
      this to its in vivo appearance during MR-guided focal cryoablation of prostate
      cancer. METHODS: A MR-compatible cryoneedle was inserted into identical gel
      phantoms (n = 3) on a 1.5 T MR system. Two fiber-optic temperature sensors were
      placed parallel to the needle. A fast 3D T1w gradient echo (GRE) sequence
      (TR/TE/FA = 4.81/1.98/6 degrees ) was used to monitor iceball progression.
      Normalized signal intensity (SI) was correlated with temperature. The same T1w
      sequence was used during MR-guided prostate cryoablation in ten consecutive
      patients at the authors' institution. In vivo findings were quantitatively
      compared to the phantom data. RESULTS: In the phantom study, the cryoablation
      iceball appeared in the T1w MR images as a sharply delineated signal void. A 2.2
      +/- 0.2 mm wide hyperintense rim directly surrounded the iceball at cooled but
      nonfreezing temperatures (<20  degrees C) in the gel. Normalized SI was maximum
      at 8.4 +/- 2.4  degrees C, showing a 35.6%-43.0% (mean 40.5%) increase with
      respect to baseline before cooling. In the clinical procedures, the same image
      contrast was observed in vivo in all patients. In vivo, width of the hyperintense
      rim was 1.6 +/- 0.6 mm. Normalized SI increases with respect to nontreated
      prostate ranged 28.4%-55.6% (mean 36.8%). On quantitative analysis, normalized SI
      changes along a linear region of interest from surrounding tissue onto the
      iceball center were similar between the patients and phantom setting (root mean
      square difference 0.06). CONCLUSIONS: The hyperintense rim around the iceball in
      fast T1w GRE images corresponded to cooled but nonfreezing temperatures (<20 
      degrees C) proximal to the frozen zone. The same image contrast was observed both
      in a phantom study as well as in vivo in the human prostate during cryotherapy.
      Potentially, monitoring of this rim could be useful in order to maintain a safe
      margin from at-risk tissues during MR-guided prostate cryoablation procedures.

PMID- 25370659
TI  - Harmonic analysis for the characterization and correction of geometric distortion
      in MRI.
AB  - PURPOSE: Magnetic resonance imaging (MRI) is gaining widespread use in radiation
      therapy planning, patient setup verification, and real-time guidance of radiation
      delivery. Successful implementation of these technologies relies on the
      development of simple and efficient methods to characterize and monitor the
      geometric distortions arising due to system imperfections and gradient
      nonlinearities. To this end, the authors present the theory and validation of a
      novel harmonic approach to the quantification of system-related distortions in
      MRI. METHODS: The theory of spatial encoding in MRI is applied to demonstrate
      that the 3D distortion vector field (DVF) is given by the solution of a second
      order boundary value problem (BVP). This BVP is comprised of Laplace's equation
      and a limited measurement of the distortion on the boundary of a specified region
      of interest (ROI). An analytical series expansion solving this BVP within a
      spherical ROI is obtained, and a statistical uncertainty analysis is performed to
      determine how random errors in the boundary measurements propagate to the ROI
      interior. This series expansion is then evaluated to obtain volumetric DVF
      mappings that are compared to reference data obtained on a 3 T full-body scanner.
      This validation is performed within two spheres of 20 cm diameter (one centered
      at the scanner origin and the other offset +3 cm along each of the transverse
      directions). Initially, a high-order mapping requiring measurements at 5810
      boundary points is used. Then, after exploring the impact of the boundary
      sampling density and the effect of series truncation, a reduced-order mapping
      requiring measurements at 302 boundary points is evaluated. RESULTS: The
      volumetric DVF mappings obtained from the harmonic analysis are in good agreement
      with the reference data. Following distortion correction using the high-order
      mapping, the authors estimate a reduction in the mean distortion magnitude from
      0.86 to 0.42 mm and from 0.93 to 0.39 mm within the central and offset ROIs,
      respectively. In addition, the fraction of points with a distortion magnitude
      greater than 1 mm is reduced from 35.6% to 2.8% and from 40.4% to 1.5%,
      respectively. Similarly, following correction using the reduced-order mapping,
      the mean distortion magnitude reduces to 0.45-0.42 mm within the central and
      offset ROIs, and the fraction of points with a distortion magnitude greater than
      1 mm is reduced to 2.8% and 1.5%, respectively. CONCLUSIONS: A novel harmonic
      approach to the characterization of system-related distortions in MRI is
      presented. This method permits a complete and accurate mapping of the DVF within
      a specified ROI using a limited measurement of the distortion on the ROI
      boundary. This technique eliminates the requirement to exhaustively sample the
      DVF at a dense 3D array of points, thereby permitting the design of simple,
      inexpensive phantoms that may incorporate additional modules for auxiliary
      quality assurance objectives.

PMID- 25370658
TI  - Electrostatic focal spot correction for x-ray tubes operating in strong magnetic
      fields.
AB  - PURPOSE: A close proximity hybrid x-ray/magnetic resonance (XMR) imaging system
      offers several critical advantages over current XMR system installations that
      have large separation distances (~5 m) between the imaging fields of view. The
      two imaging systems can be placed in close proximity to each other if an x-ray
      tube can be designed to be immune to the magnetic fringe fields outside of the MR
      bore. One of the major obstacles to robust x-ray tube design is correcting for
      the effects of the MR fringe field on the x-ray tube focal spot. Any fringe field
      component orthogonal to the x-ray tube electric field leads to electron drift
      altering the path of the electron trajectories. METHODS: The method proposed in
      this study to correct for the electron drift utilizes an external electric field
      in the direction of the drift. The electric field is created using two electrodes
      that are positioned adjacent to the cathode. These electrodes are biased with
      positive and negative potential differences relative to the cathode. The design
      of the focusing cup assembly is constrained primarily by the strength of the MR
      fringe field and high voltage standoff distances between the anode, cathode, and
      the bias electrodes. From these constraints, a focusing cup design suitable for
      the close proximity XMR system geometry is derived, and a finite element model of
      this focusing cup geometry is simulated to demonstrate efficacy. A Monte Carlo
      simulation is performed to determine any effects of the modified focusing cup
      design on the output x-ray energy spectrum. RESULTS: An orthogonal fringe field
      magnitude of 65 mT can be compensated for using bias voltages of +15 and -20 kV.
      These bias voltages are not sufficient to completely correct for larger
      orthogonal field magnitudes. Using active shielding coils in combination with the
      bias electrodes provides complete correction at an orthogonal field magnitude of
      88.1 mT. Introducing small fields (<10 mT) parallel to the x-ray tube electric
      field in addition to the orthogonal field does not affect the electrostatic
      correction technique. However, rotation of the x-ray tube by 30 degrees  toward
      the MR bore increases the parallel magnetic field magnitude (~72 mT). The
      presence of this larger parallel field along with the orthogonal field leads to
      incomplete correction. Monte Carlo simulations demonstrate that the mean energy
      of the x-ray spectrum is not noticeably affected by the electrostatic correction,
      but the output flux is reduced by 7.5%. CONCLUSIONS: The maximum orthogonal
      magnetic field magnitude that can be compensated for using the proposed design is
      65 mT. Larger orthogonal field magnitudes cannot be completely compensated for
      because a pure electrostatic approach is limited by the dielectric strength of
      the vacuum inside the x-ray tube insert. The electrostatic approach also suffers
      from limitations when there are strong magnetic fields in both the orthogonal and
      parallel directions because the electrons prefer to stay aligned with the
      parallel magnetic field. These challenging field conditions can be addressed by
      using a hybrid correction approach that utilizes both active shielding coils and
      biasing electrodes.

PMID- 25370661
TI  - Evaluating the purity of a (57)Co flood source by PET.
AB  - PURPOSE: Flood sources of (57)Co are commonly used for quality control of gamma
      cameras. Flood uniformity may be affected by the contaminants (56)Co and (58)Co,
      which emit higher energy photons. Although vendors specify a maximum combined
      (56)Co and (58)Co activity, a convenient test for flood source purity that is
      feasible in a clinical environment would be desirable. METHODS: Both (56)Co and
      (58)Co emit positrons with branching 19.6% and 14.9%, respectively. As is known
      from (90)Y imaging, a positron emission tomography (PET) scanner is capable of
      quantitatively imaging very weak positron emission in a high single-photon
      background. To evaluate this approach, two (57)Co flood sources were scanned with
      a clinical PET/CT multiple times over a period of months. The (56)Co and (58)Co
      activity was clearly visible in the reconstructed PET images. Total impurity
      activity was quantified from the PET images after background subtraction of
      prompt gamma coincidences. RESULTS: Time-of-flight PET reconstruction was highly
      beneficial for accurate image quantification. Repeated measurements of the
      positron-emitting impurities showed excellent agreement with an exponential decay
      model. For both flood sources studied, the fit parameters indicated a zero
      intercept and a decay half-life consistent with a mixture of (56)Co and (58)Co.
      The total impurity activity at the reference date was estimated to be 0.06% and
      0.07% for the two sources, which was consistent with the vendor's specification
      of <0.12%. CONCLUSIONS: The robustness of the repeated measurements and a
      thorough analysis of the detector corrections and physics suggest that the
      accuracy is acceptable and that the technique is feasible. Further work is needed
      to validate the accuracy of this technique with a calibrated high resolution
      gamma spectrometer as a gold standard, which was not available for this study,
      and for other PET detector models.

PMID- 25370660
TI  - Multipinhole collimator with 20 apertures for a brain SPECT application.
AB  - PURPOSE: Several new technologies for single photon emission computed tomography
      (SPECT) instrumentation with parallel-hole collimation have been proposed to
      improve detector sensitivity and signal collection efficiency. Benefits from
      improved signal efficiency include shorter acquisition times and lower dose
      requirements. In this paper, the authors show a possibility of over an order of
      magnitude enhancement in photon detection efficiency (from 7.6 * 10(-5) to 1.6 *
      10(-3)) for dopamine transporter (DaT) imaging of the striatum over the
      conventional SPECT parallel-hole collimators by use of custom-designed 20
      multipinhole (20-MPH) collimators with apertures of 0.75 cm diameter. METHODS:
      Quantifying specific binding ratio (SBR) of (123)I-ioflupane or (123)I
      iometopane's signal at the striatal region is a common brain imaging method to
      confirm the diagnosis of the Parkinson's disease. The authors performed imaging
      of a striatal phantom filled with aqueous solution of I-123 and compared camera
      recovery ratios of SBR acquired between low-energy high-resolution (LEHR)
      parallel-hole collimators and 20-MPH collimators. RESULTS: With only two-thirds
      of total acquisition time (20 min against 30 min), a comparable camera recovery
      ratio of SBR was achieved using 20-MPH collimators in comparison to that from the
      LEHR collimator study. CONCLUSIONS: Their systematic analyses showed that the 20
      MPH collimator could be a promising alternative for the DaT SPECT imaging for
      brain over the traditional LEHR collimator, which could give both shorter scan
      time and improved diagnostic accuracy.

PMID- 25370662
TI  - Comparison of an alternative and existing binning methods to reduce the
      acquisition duration of 4D PET/CT.
AB  - PURPOSE: Respiratory motion is a source of artifacts that reduce image quality in
      PET. Four dimensional (4D) PET/CT is one approach to overcome this problem.
      Existing techniques to limiting the effects of respiratory motions are based on
      prospective phase binning which requires a long acquisition duration (15-25 min).
      This time is uncomfortable for the patients and limits the clinical exploitation
      of 4D PET/CT. In this work, the authors evaluated an existing method and an
      alternative retrospective binning method to reduce the acquisition duration of 4D
      PET/CT. METHODS: The authors studied an existing mixed-amplitude binning (MAB)
      method and an alternative binning method by mixed-phases (MPhB). Before
      implementing MPhB, they analyzed the regularity of the breathing patterns in
      patients. They studied the breathing signal drift and missing CT slices that
      could be challenging for implementing MAB. They compared the performance of MAB
      and MPhB with current binning methods to measure the maximum uptake, internal
      volume, and maximal range of tumor motion. RESULTS: MPhB can be implemented
      depending on an optimal phase (in average, the exhalation peak phase -4.1% of the
      entire breathing cycle duration). Signal drift of patients was in average 35%
      relative to the breathing amplitude. Even after correcting this drift, MAB was
      feasible in 4D CT for only 64% of patients. No significant differences appeared
      between the different binning methods to measure the maximum uptake, internal
      volume, and maximal range of tumor motion. The authors also determined the
      inaccuracies of MAB and MPhB to measure the maximum amplitude of tumor motion
      with three bins (less than 3 mm for movement inferior to 12 mm, up to 6.4 mm for
      a 21 mm movement). CONCLUSIONS: The authors proposed an alternative binning
      method by mixed-phase binning that halves the acquisition duration of 4D PET/CT.
      Mixed-amplitude binning was challenging because of signal drift and missing CT
      slices. They showed that more than three bins were necessary for a more accurate
      measurement of the maximum amplitude of the tumor motion. However, the current 4D
      CT technology limits the increase of the number of bins in 4D PET/CT because of
      missing CT slices. One can reconstruct 4D PET images with more bins but without
      attenuation/scatter correction.

PMID- 25370663
TI  - A hardware investigation of robotic SPECT for functional and molecular imaging
      onboard radiation therapy systems.
AB  - PURPOSE: To construct a robotic SPECT system and to demonstrate its capability to
      image a thorax phantom on a radiation therapy flat-top couch, as a step toward
      onboard functional and molecular imaging in radiation therapy. METHODS: A robotic
      SPECT imaging system was constructed utilizing a gamma camera detector (Digirad
      2020tc) and a robot (KUKA KR150 L110 robot). An imaging study was performed with
      a phantom (PET CT Phantom(TM)), which includes five spheres of 10, 13, 17, 22,
      and 28 mm diameters. The phantom was placed on a flat-top couch. SPECT
      projections were acquired either with a parallel-hole collimator or a single
      pinhole collimator, both without background in the phantom and with background at
      1/10th the sphere activity concentration. The imaging trajectories of parallel
      hole and pinhole collimated detectors spanned 180 degrees  and 228 degrees ,
      respectively. The pinhole detector viewed an off-centered spherical common volume
      which encompassed the 28 and 22 mm spheres. The common volume for parallel-hole
      system was centered at the phantom which encompassed all five spheres in the
      phantom. The maneuverability of the robotic system was tested by navigating the
      detector to trace the phantom and flat-top table while avoiding collision and
      maintaining the closest possible proximity to the common volume. The robot base
      and tool coordinates were used for image reconstruction. RESULTS: The robotic
      SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT
      detectors in close proximity to the phantom, minimizing impact of the flat-top
      couch on detector radius of rotation. Without background, all five spheres were
      visible in the reconstructed parallel-hole image, while four spheres, all except
      the smallest one, were visible in the reconstructed pinhole image. With
      background, three spheres of 17, 22, and 28 mm diameters were readily observed
      with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameters)
      were readily observed in the pinhole region-of-interest imaging. CONCLUSIONS:
      Onboard SPECT could be achieved by a robot maneuvering a SPECT detector about
      patients in position for radiation therapy on a flat-top couch. The robot
      inherent coordinate frames could be an effective means to estimate detector pose
      for use in SPECT image reconstruction.

PMID- 25370664
TI  - A multifractal approach to space-filling recovery for PET quantification.
AB  - PURPOSE: A new image-based methodology is developed for estimating the apparent
      space-filling properties of an object of interest in PET imaging without need for
      a robust segmentation step and used to recover accurate estimates of total lesion
      activity (TLA). METHODS: A multifractal approach and the fractal dimension are
      proposed to recover the apparent space-filling index of a lesion (tumor volume,
      TV) embedded in nonzero background. A practical implementation is proposed, and
      the index is subsequently used with mean standardized uptake value (SUV mean) to
      correct TLA estimates obtained from approximate lesion contours. The methodology
      is illustrated on fractal and synthetic objects contaminated by partial volume
      effects (PVEs), validated on realistic (18)F-fluorodeoxyglucose PET simulations
      and tested for its robustness using a clinical (18)F-fluorothymidine PET test
      retest dataset. RESULTS: TLA estimates were stable for a range of resolutions
      typical in PET oncology (4-6 mm). By contrast, the space-filling index and
      intensity estimates were resolution dependent. TLA was generally recovered within
      15% of ground truth on postfiltered PET images affected by PVEs. Volumes were
      recovered within 15% variability in the repeatability study. Results indicated
      that TLA is a more robust index than other traditional metrics such as SUV mean
      or TV measurements across imaging protocols. CONCLUSIONS: The fractal procedure
      reported here is proposed as a simple and effective computational alternative to
      existing methodologies which require the incorporation of image preprocessing
      steps (i.e., partial volume correction and automatic segmentation) prior to
      quantification.

PMID- 25370665
TI  - Effect of respiratory motion on internal radiation dosimetry.
AB  - PURPOSE: Estimation of the radiation dose to internal organs is essential for the
      assessment of radiation risks and benefits to patients undergoing diagnostic and
      therapeutic nuclear medicine procedures including PET. Respiratory motion induces
      notable internal organ displacement, which influences the absorbed dose for
      external exposure to radiation. However, to their knowledge, the effect of
      respiratory motion on internal radiation dosimetry has never been reported
      before. METHODS: Thirteen computational models representing the adult male at
      different respiratory phases corresponding to the normal respiratory cycle were
      generated from the 4D dynamic XCAT phantom. Monte Carlo calculations were
      performed using the mcnp transport code to estimate the specific absorbed
      fractions (SAFs) of monoenergetic photons/electrons, the S-values of common
      positron-emitting radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82, Y
      86, and I-124), and the absorbed dose of (18)F-fluorodeoxyglucose ((18)F-FDG) in
      28 target regions for both the static (average of dynamic frames) and dynamic
      phantoms. RESULTS: The self-absorbed dose for most organs/tissues is only
      slightly influenced by respiratory motion. However, for the lung, the self
      absorbed SAF is about 11.5% higher at the peak exhale phase than the peak inhale
      phase for photon energies above 50 keV. The cross-absorbed dose is obviously
      affected by respiratory motion for many combinations of source-target pairs. The
      cross-absorbed S-values for the heart contents irradiating the lung are about
      7.5% higher in the peak exhale phase than the peak inhale phase for different
      positron-emitting radionuclides. For (18)F-FDG, organ absorbed doses are less
      influenced by respiratory motion. CONCLUSIONS: Respiration-induced volume
      variations of the lungs and the repositioning of internal organs affect the self
      absorbed dose of the lungs and cross-absorbed dose between organs in internal
      radiation dosimetry. The dynamic anatomical model provides more accurate internal
      radiation dosimetry estimates for the lungs and abdominal organs based on
      realistic modeling of respiratory motion. This work also contributes to a better
      understanding of model-induced uncertainties in internal radiation dosimetry.

PMID- 25370666
TI  - Development and evaluation of convergent and accelerated penalized SPECT image
      reconstruction methods for improved dose-volume histogram estimation in
      radiopharmaceutical therapy.
AB  - PURPOSE: Three-dimensional (3D) dosimetry has the potential to provide better
      prediction of response of normal tissues and tumors and is based on 3D estimates
      of the activity distribution in the patient obtained from emission tomography.
      Dose-volume histograms (DVHs) are an important summary measure of 3D dosimetry
      and a widely used tool for treatment planning in radiation therapy. Accurate
      estimates of the radioactivity distribution in space and time are desirable for
      accurate 3D dosimetry. The purpose of this work was to develop and demonstrate
      the potential of penalized SPECT image reconstruction methods to improve DVHs
      estimates obtained from 3D dosimetry methods. METHODS: The authors developed
      penalized image reconstruction methods, using maximum a posteriori (MAP)
      formalism, which intrinsically incorporate regularization in order to control
      noise and, unlike linear filters, are designed to retain sharp edges. Two priors
      were studied: one is a 3D hyperbolic prior, termed single-time MAP (STMAP), and
      the second is a 4D hyperbolic prior, termed cross-time MAP (CTMAP), using both
      the spatial and temporal information to control noise. The CTMAP method assumed
      perfect registration between the estimated activity distributions and projection
      datasets from the different time points. Accelerated and convergent algorithms
      were derived and implemented. A modified NURBS-based cardiac-torso phantom with a
      multicompartment kidney model and organ activities and parameters derived from
      clinical studies were used in a Monte Carlo simulation study to evaluate the
      methods. Cumulative dose-rate volume histograms (CDRVHs) and cumulative DVHs
      (CDVHs) obtained from the phantom and from SPECT images reconstructed with both
      the penalized algorithms and OS-EM were calculated and compared both
      qualitatively and quantitatively. The STMAP method was applied to patient data
      and CDRVHs obtained with STMAP and OS-EM were compared qualitatively. RESULTS:
      The results showed that the penalized algorithms substantially improved the CDRVH
      and CDVH estimates for large organs such as the liver compared to optimally
      postfiltered OS-EM. For example, the mean squared errors (MSEs) of the CDRVHs for
      the liver at 5 h postinjection obtained with CTMAP and STMAP were about 15% and
      17%, respectively, of the MSEs obtained with optimally filtered OS-EM. For the
      CDVH estimates, the MSEs obtained with CTMAP and STMAP were about 16% and 19%,
      respectively, of the MSEs from OS-EM. For the kidneys and renal cortices, larger
      residual errors were observed for all algorithms, likely due to partial volume
      effects. The STMAP method showed promising qualitative results when applied to
      patient data. CONCLUSIONS: Penalized image reconstruction methods were developed
      and evaluated through a simulation study. The study showed that the MAP
      algorithms substantially improved CDVH estimates for large organs such as the
      liver compared to optimally postfiltered OS-EM reconstructions. For small organs
      with fine structural detail such as the kidneys, a large residual error was
      observed for both MAP algorithms and OS-EM. While CTMAP provided marginally
      better MSEs than STMAP, given the extra effort needed to handle misregistration
      of images at different time points in the algorithm and the potential impact of
      residual misregistration, 3D regularization methods, such as that used in STMAP,
      appear to be a more practical choice.

PMID- 25370667
TI  - Adaptation of the modified Bouc-Wen model to compensate for hysteresis in
      respiratory motion for the list-mode binning of cardiac SPECT and PET
      acquisitions: testing using MRI.
AB  - PURPOSE: Binning list-mode acquisitions as a function of a surrogate signal
      related to respiration has been employed to reduce the impact of respiratory
      motion on image quality in cardiac emission tomography (SPECT and PET). Inherent
      in amplitude binning is the assumption that there is a monotonic relationship
      between the amplitude of the surrogate signal and respiratory motion of the
      heart. This assumption is not valid in the presence of hysteresis when heart
      motion exhibits a different relationship with the surrogate during inspiration
      and expiration. The purpose of this study was to investigate the novel approach
      of using the Bouc-Wen (BW) model to provide a signal accounting for hysteresis
      when binning list-mode data with the goal of thereby improving motion correction.
      The study is based on the authors' previous observations that hysteresis between
      chest and abdomen markers was indicative of hysteresis between abdomen markers
      and the internal motion of the heart. METHODS: In 19 healthy volunteers, they
      determined the internal motion of the heart and diaphragm in the superior
      inferior direction during free breathing using MRI navigators. A visual tracking
      system (vts) synchronized with MRI acquisition tracked the anterior-posterior
      motions of external markers placed on the chest and abdomen. These data were
      employed to develop and test the Bouc-Wen model by inputting the vts derived
      chest and abdomen motions into it and using the resulting output signals as
      surrogates for cardiac motion. The data of the volunteers were divided into
      training and testing sets. The training set was used to obtain initial values for
      the model parameters for all of the volunteers in the set, and for set members
      based on whether they were or were not classified as exhibiting hysteresis using
      a metric derived from the markers. These initial parameters were then employed
      with the testing set to estimate output signals. Pearson's linear correlation
      coefficient between the abdomen, chest, average of chest and abdomen markers, and
      Bouc-Wen derived signals versus the true internal motion of the heart from MRI
      was used to judge the signals match to the heart motion. RESULTS: The results
      show that the Bouc-Wen model generated signals demonstrated strong correlation
      with the heart motion. This correlation was slightly larger on average than that
      of the external surrogate signals derived from the abdomen marker, and average of
      the abdomen and chest markers, but was not statistically significantly different
      from them. CONCLUSIONS: The results suggest that the proposed model has the
      potential to be a unified framework for modeling hysteresis in respiratory motion
      in cardiac perfusion studies and beyond.

PMID- 25370668
TI  - Quantitative evaluation of atrial radio frequency ablation using intracardiac
      shear-wave elastography.
AB  - PURPOSE: Radio frequency catheter ablation (RFCA) is a well-established clinical
      procedure for the treatment of atrial fibrillation (AF) but suffers from a low
      single-procedure success rate. Recurrence of AF is most likely attributable to
      discontinuous or nontransmural ablation lesions. Yet, despite this urgent
      clinical need, there is no clinically available imaging modality that can
      reliably map the lesion transmural extent in real time. In this study, the
      authors demonstrated the feasibility of shear-wave elastography (SWE) to map
      quantitatively the stiffness of RFCA-induced thermal lesions in cardiac tissues
      in vitro and in vivo using an intracardiac transducer array. METHODS: SWE was
      first validated in ex vivo porcine ventricular samples (N = 5). Both B-mode
      imaging and SWE were performed on normal cardiac tissue before and after RFCA.
      Areas of the lesions were determined by tissue color change with gross pathology
      and compared against the SWE stiffness maps. SWE was then performed in vivo in
      three sheep (N = 3). First, the stiffness of normal atrial tissues was assessed
      quantitatively as well as its variation during the cardiac cycle. SWE was then
      performed in atrial tissue after RFCA. RESULTS: A large increase in stiffness was
      observed in ablated ex vivo regions (average shear modulus across samples in
      normal tissue: 22 +/- 5 kPa, average shear-wave speed (ct): 4.5 +/- 0.4 m s(-1)
      and in determined ablated zones: 99 +/- 17 kPa, average ct: 9.0 +/- 0.5 m s(-1)
      for a mean shear modulus increase ratio of 4.5 +/- 0.9). In vivo, a threefold
      increase of the shear modulus was measured in the ablated regions, and the lesion
      extension was clearly visible on the stiffness maps. CONCLUSIONS: By its
      quantitative and real-time capabilities, Intracardiac SWE is a promising
      intraoperative imaging technique for the evaluation of thermal ablation during
      RFCA.

PMID- 25370669
TI  - Spatiospectral denoising framework for multispectral optoacoustic imaging based
      on sparse signal representation.
AB  - PURPOSE: One of the major challenges in dynamic multispectral optoacoustic
      imaging is its relatively low signal-to-noise ratio which often requires
      repetitive signal acquisition and averaging, thus limiting imaging rate. The
      development of denoising methods which prevent the need for signal averaging in
      time presents an important goal for advancing the dynamic capabilities of the
      technology. METHODS: In this paper, a denoising method is developed for
      multispectral optoacoustic imaging which exploits the implicit sparsity of
      multispectral optoacoustic signals both in space and in spectrum. Noise
      suppression is achieved by applying thresholding on a combined wavelet-Karhunen
      Loeve representation in which multispectral optoacoustic signals appear
      particularly sparse. The method is based on inherent characteristics of
      multispectral optoacoustic signals of tissues, offering promise for general
      application in different incarnations of multispectral optoacoustic systems.
      RESULTS: The performance of the proposed method is demonstrated on mouse images
      acquired in vivo for two common additive noise sources: time-varying parasitic
      signals and white noise. In both cases, the proposed method shows considerable
      improvement in image quality in comparison to previously published denoising
      strategies that do not consider multispectral information. CONCLUSIONS: The
      suggested denoising methodology can achieve noise suppression with minimal signal
      loss and considerably outperforms previously proposed denoising strategies,
      holding promise for advancing the dynamic capabilities of multispectral
      optoacoustic imaging while retaining image quality.

PMID- 25370670
TI  - Spatiotemporal filtering of MR-temperature artifacts arising from bowel motion
      during transurethral MR-HIFU.
AB  - PURPOSE: Transurethral MR-HIFU is a minimally invasive image-guided treatment for
      localized prostate cancer that enables precise targeting of tissue within the
      gland. The treatment is performed within a clinical MRI to obtain real-time MR
      thermometry used as an active feedback to control the spatial heating pattern in
      the prostate and to monitor for potential damage to surrounding tissues. This
      requires that the MR thermometry measurements are an accurate representation of
      the true tissue temperature. The proton resonance frequency shift thermometry
      method used is sensitive to tissue motion and changes in the local magnetic
      susceptibility that can be caused by the motion of air bubbles in the rectum,
      which can impact the performance of transurethral MR-HIFU in these regions of the
      gland. METHODS: A method is proposed for filtering of temperature artifacts based
      on the temporal variance of the temperature, using empirical and dynamic
      positional knowledge of the ultrasonic heating beam, and an estimation of the
      measurement noise. A two-step correction strategy is introduced which eliminates
      artifact-detected temperature variations while keeping the noise level low
      through spatial averaging. RESULTS: The filter has been evaluated by
      postprocessing data from five human transurethral ultrasound treatments. The two
      step correction process led to reduced final temperature standard deviation in
      the prostate and rectum areas where the artifact was located, without negatively
      affecting areas distal to the artifact. The performance of the filter was also
      found to be consistent across all six of the data sets evaluated. The evaluation
      of the detection criterion parameter M determined that a value of M = 3 achieves
      a conservative filter with minimal loss of spatial resolution during the process.
      CONCLUSIONS: The filter was able to remove most artifacts due to the presence of
      moving air bubbles in the rectum during transurethral MR-HIFU. A quantitative
      estimation of the filter capabilities shows a systematic improvement in the
      standard deviation of the corrected temperature maps in the rectum zone as well
      as in the entire acquired slice.

PMID- 25370671
TI  - CT imaging during microwave ablation: analysis of spatial and temporal tissue
      contraction.
AB  - PURPOSE: To analyze the spatial distribution and temporal development of liver
      tissue contraction during high-temperature ablation by using intraprocedural
      computed tomography (CT) imaging. METHODS: A total of 46 aluminum fiducial
      markers were positioned in a 60 * 45 mm grid, in a single plane, around a
      microwave ablation antenna in each of six ex vivo bovine liver samples. Ablations
      were performed for 10 min at 100 W. CT data of the liver sample were acquired
      every 30 s during ablation. Fiducial motion between acquisitions was tracked in
      postprocessing and used to calculate measures of tissue contraction and
      contraction rates. The spatial distribution and temporal evolution of contraction
      were analyzed. RESULTS: Fiducial displacement indicated that the zone measured
      postablation was 8.2 +/- 1.8 mm (~20%) smaller in the radial direction and 7.1 +/
      1.0 mm (~10%) shorter in the longitudinal direction than the preablation tissue
      dimension. Therefore, the total ablation volume was reduced from its preablation
      value by approximately 45%. Very little longitudinal contraction was noted in the
      distal portion of the ablation zone. Central tissues contracted more than 60%,
      which was near an estimated limit of ~70% based on initial water content. More
      peripheral tissues contracted only 15% in any direction. Contraction rates peaked
      during the first 60 s of heating with a roughly exponential decay over time.
      CONCLUSIONS: Ablation zones measured posttreatment are significantly smaller than
      the pretreatment tissue dimensions. Tissue contraction is spatially dependent,
      with the greatest effect occurring in the central ablation zone. Contraction rate
      peaks early and decays over time.

PMID- 25370672
TI  - A method to estimate the fractional fat volume within a ROI of a breast biopsy
      for WAXS applications: animal tissue evaluation.
AB  - PURPOSE: To develop a method to estimate the mean fractional volume of fat (nu
      fat) within a region of interest (ROI) of a tissue sample for wide-angle x-ray
      scatter (WAXS) applications. A scatter signal from the ROI was obtained and use
      of nu-fat in a WAXS fat subtraction model provided a way to estimate the
      differential linear scattering coefficient MUs of the remaining fatless tissue.
      METHODS: The efficacy of the method was tested using animal tissue from a local
      butcher shop. Formalin fixed samples, 5 mm in diameter 4 mm thick, were prepared.
      The two main tissue types were fat and meat (fibrous). Pure as well as composite
      samples consisting of a mixture of the two tissue types were analyzed. For the
      latter samples, nufat for the tissue columns of interest were extracted from
      corresponding pixels in CCD digital x-ray images using a calibration curve. The
      means nu-fat were then calculated for use in a WAXS fat subtraction model. For
      the WAXS measurements, the samples were interrogated with a 2.7 mm diameter 50 kV
      beam and the 6 degrees  scattered photons were detected with a CdTe detector
      subtending a solid angle of 7.75 * 10(-5) sr. Using the scatter spectrum, an
      estimate of the incident spectrum, and a scatter model, MUs was determined for
      the tissue in the ROI. For the composite samples, a WAXS fat subtraction model
      was used to estimate the MUs of the fibrous tissue in the ROI. This signal was
      compared to MUs of fibrous tissue obtained using a pure fibrous sample. RESULTS:
      For chicken and beef composites, nu-fat=0.33+/-0.05 and 0.32 +/- 0.05,
      respectively. The subtractions of these fat components from the WAXS composite
      signals provided estimates of MUs for chicken and beef fibrous tissue. The
      differences between the estimates and MUs of fibrous obtained with a pure sample
      were calculated as a function of the momentum transfer x. A t-test showed that
      the mean of the differences did not vary from zero in a statistically significant
      way thereby validating the methods. CONCLUSIONS: The methodology to estimate nu
      fat in a ROI of a tissue sample via CCD x-ray imaging was quantitatively
      accurate. The WAXS fat subtraction model allowed MUs of fibrous tissue to be
      obtained from a ROI which had some fat. The fat estimation method coupled with
      the WAXS models can be used to compare MUs coefficients of fibroglandular and
      cancerous breast tissue.

PMID- 25370673
TI  - Validation of a stereo camera system to quantify brain deformation due to
      breathing and pulsatility.
AB  - PURPOSE: A new stereo vision system is presented to quantify brain shift and
      pulsatility in open-skull neurosurgeries. METHODS: The system is endowed with
      hardware and software synchronous image acquisition with timestamp embedding in
      the captured images, a brain surface oriented feature detection, and a tracking
      subroutine robust to occlusions and outliers. A validation experiment for the
      stereo vision system was conducted against a gold-standard optical tracking
      system, Optotrak CERTUS. A static and dynamic analysis of the stereo camera
      tracking error was performed tracking a customized object in different positions,
      orientations, linear, and angular speeds. RESULTS: The system is able to detect
      an immobile object position and orientation with a maximum error of 0.5 mm and
      1.6 degrees  in all depth of field, and tracking a moving object until 3 mm/s
      with a median error of 0.5 mm. Three stereo video acquisitions were recorded from
      a patient, immediately after the craniotomy. The cortical pulsatile motion was
      captured and is represented in the time and frequency domain. The amplitude of
      motion of the cloud of features' center of mass was inferior to 0.8 mm. Three
      distinct peaks are identified in the fast Fourier transform analysis related to
      the sympathovagal balance, breathing, and blood pressure with 0.03-0.05, 0.2, and
      1 Hz, respectively. CONCLUSIONS: The stereo vision system presented is a precise
      and robust system to measure brain shift and pulsatility with an accuracy
      superior to other reported systems.

PMID- 25370674
TI  - Spatially varying accuracy and reproducibility of prostate segmentation in
      magnetic resonance images using manual and semiautomated methods.
AB  - PURPOSE: Three-dimensional (3D) prostate image segmentation is useful for cancer
      diagnosis and therapy guidance, but can be time-consuming to perform manually and
      involves varying levels of difficulty and interoperator variability within the
      prostatic base, midgland (MG), and apex. In this study, the authors measured
      accuracy and interobserver variability in the segmentation of the prostate on T2
      weighted endorectal magnetic resonance (MR) imaging within the whole gland (WG),
      and separately within the apex, midgland, and base regions. METHODS: The authors
      collected MR images from 42 prostate cancer patients. Prostate border delineation
      was performed manually by one observer on all images and by two other observers
      on a subset of ten images. The authors used complementary boundary-, region-, and
      volume-based metrics [mean absolute distance (MAD), Dice similarity coefficient
      (DSC), recall rate, precision rate, and volume difference (DeltaV)] to elucidate
      the different types of segmentation errors that they observed. Evaluation for
      expert manual and semiautomatic segmentation approaches was carried out. Compared
      to manual segmentation, the authors' semiautomatic approach reduces the necessary
      user interaction by only requiring an indication of the anteroposterior
      orientation of the prostate and the selection of prostate center points on the
      apex, base, and midgland slices. Based on these inputs, the algorithm identifies
      candidate prostate boundary points using learned boundary appearance
      characteristics and performs regularization based on learned prostate shape
      information. RESULTS: The semiautomated algorithm required an average of 30 s of
      user interaction time (measured for nine operators) for each 3D prostate
      segmentation. The authors compared the segmentations from this method to manual
      segmentations in a single-operator (mean whole gland MAD = 2.0 mm, DSC = 82%,
      recall = 77%, precision = 88%, and DeltaV = - 4.6 cm(3)) and multioperator study
      (mean whole gland MAD = 2.2 mm, DSC = 77%, recall = 72%, precision = 86%, and
      DeltaV = - 4.0 cm(3)). These results compared favorably with observed differences
      between manual segmentations and a simultaneous truth and performance level
      estimation reference for this data set (whole gland differences as high as MAD =
      3.1 mm, DSC = 78%, recall = 66%, precision = 77%, and DeltaV = 15.5 cm(3)). The
      authors found that overall, midgland segmentation was more accurate and
      repeatable than the segmentation of the apex and base, with the base posing the
      greatest challenge. CONCLUSIONS: The main conclusions of this study were that (1)
      the semiautomated approach reduced interobserver segmentation variability; (2)
      the segmentation accuracy of the semiautomated approach, as well as the
      accuracies of recently published methods from other groups, were within the range
      of observed expert variability in manual prostate segmentation; and (3) further
      efforts in the development of computer-assisted segmentation would be most
      productive if focused on improvement of segmentation accuracy and reduction of
      variability within the prostatic apex and base.

PMID- 25370675
TI  - Does administering iodine in radiological procedures increase patient doses?
AB  - PURPOSE: The authors investigated the changes in the pattern of energy deposition
      in tissue equivalent phantoms following the introduction of iodinated contrast
      media. METHODS: The phantom consisted of a small "contrast sphere," filled with
      water or iodinated contrast, located at the center of a 28 cm diameter water
      sphere. Monte Carlo simulations were performed using mcnp5 codes, validated by
      simulating irradiations with analytical solutions. Monoenergetic x-rays ranging
      from 35 to 150 keV were used to simulate exposures to spheres containing contrast
      agent with iodine concentrations ranging from 1 to 100 mg/ml. Relative values of
      energy imparted to the contrast sphere, as well as to the whole phantom, were
      calculated. Changes in patterns of energy deposition around the contrast sphere
      were also investigated. RESULTS: Small contrast spheres can increase local
      absorbed dose by a factor of 13, but the corresponding increase in total energy
      absorbed was negligible (<1%). The highest localized dose increases were found to
      occur at incident photon energies of about 60 keV. For a concentration of about
      10 mg/ml, typical of clinical practice, localized absorbed doses were generally
      increased by about a factor of two. At this concentration of 10 mg/ml, the
      maximum increase in total energy deposition in the phantom was only 6%. These
      simulations demonstrated that increases in contrast sphere doses were offset by
      corresponding dose reductions at distal and posterior locations. CONCLUSIONS:
      Adding iodine can result in values of localized absorbed dose increasing by more
      than an order of magnitude, but the total energy deposition is generally very
      modest (i.e., <10%). Their data show that adding iodine primarily changes the
      pattern of energy deposition in the irradiated region, rather than increasing
      patient doses per se.

PMID- 25370676
TI  - Comparative analysis of 11 different radioisotopes for palliative treatment of
      bone metastases by computational methods.
AB  - PURPOSE: Throughout the years, the palliative treatment of bone metastases using
      bone seeking radiotracers has been part of the therapeutic resources used in
      oncology, but the choice of which bone seeking agent to use is not consensual
      across sites and limited data are available comparing the characteristics of each
      radioisotope. Computational simulation is a simple and practical method to study
      and to compare a variety of radioisotopes for different medical applications,
      including the palliative treatment of bone metastases. This study aims to
      evaluate and compare 11 different radioisotopes currently in use or under
      research for the palliative treatment of bone metastases using computational
      methods. METHODS: Computational models were used to estimate the percentage of
      deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the
      probability of correct DNA repair (Monte Carlo excision repair algorithm), and
      the radiation-induced cellular effects (virtual cell radiobiology algorithm) post
      irradiation with selected particles emitted by phosphorus-32 ((32)P), strontium
      89 ((89)Sr), yttrium-90 ((90)Y ), tin-117 ((117m)Sn), samarium-153 ((153)Sm),
      holmium-166 ((166)Ho), thulium-170 ((170)Tm), lutetium-177 ((177)Lu), rhenium-186
      ((186)Re), rhenium-188 ((188)Re), and radium-223 ((223)Ra). RESULTS: (223)Ra
      alpha particles, (177)Lu beta minus particles, and (170)Tm beta minus particles
      induced the highest cell death of all investigated particles and radioisotopes.
      The cell survival fraction measured post-irradiation with beta minus particles
      emitted by (89)Sr and (153)Sm, two of the most frequently used radionuclides in
      the palliative treatment of bone metastases in clinical routine practice, was
      higher than (177)Lu beta minus particles and (223)Ra alpha particles.
      CONCLUSIONS: (223)Ra and (177)Lu hold the highest potential for palliative
      treatment of bone metastases of all radioisotopes compared in this study. Data
      reported here may prompt future in vitro and in vivo experiments comparing
      different radionuclides for palliative treatment of bone metastases, raise the
      need for the careful rethinking of the current widespread clinical use of (89)Sr
      and (153)Sm, and perhaps strengthen the use of (223)Ra and (177)Lu in the
      palliative treatment of bone metastases.

PMID- 25370677
TI  - Effect of improved TLD dosimetry on the determination of dose rate constants for
      (125)I and (103)Pd brachytherapy seeds.
AB  - PURPOSE: To more accurately account for the relative intrinsic energy dependence
      and relative absorbed-dose energy dependence of TLDs when used to measure dose
      rate constants (DRCs) for (125)I and (103)Pd brachytherapy seeds, to thereby
      establish revised "measured values" for all seeds and compare the revised values
      with Monte Carlo and consensus values. METHODS: The relative absorbed-dose energy
      dependence, f(rel), for TLDs and the phantom correction, Pphant, are calculated
      for (125)I and (103)Pd seeds using the EGSnrc BrachyDose and DOSXYZnrc codes. The
      original energy dependence and phantom corrections applied to DRC measurements
      are replaced by calculated (f(rel))(-1) and Pphant values for 24 different seed
      models. By comparing the modified measured DRCs to the MC values, an appropriate
      relative intrinsic energy dependence, kbq (rel), is determined. The new Pphant
      values and relative absorbed-dose sensitivities, SAD (rel), calculated as the
      product of (f(rel))(-1) and (kbq (rel))(-1), are used to individually revise the
      measured DRCs for comparison with Monte Carlo calculated values and TG-43U1 or TG
      43U1S1 consensus values. RESULTS: In general, f(rel) is sensitive to the energy
      spectra and models of the brachytherapy seeds. Values may vary up to 8.4% among
      (125)I and (103)Pd seed models and common TLD shapes. Pphant values depend
      primarily on the isotope used. Deduced (kbq (rel))(-1) values are 1.074 +/- 0.015
      and 1.084 +/- 0.026 for (125)I and (103)Pd seeds, respectively. For (1 mm)(3)
      chips, this implies an overall absorbed-dose sensitivity relative to (60)Co or 6
      MV calibrations of 1.51 +/- 1% and 1.47 +/- 2% for (125)I and (103)Pd seeds,
      respectively, as opposed to the widely used value of 1.41. Values of Pphant
      calculated here have much lower statistical uncertainties than literature values,
      but systematic uncertainties from density and composition uncertainties are
      significant. Using these revised values with the literature's DRC measurements,
      the average discrepancies between revised measured values and Monte Carlo values
      are 1.2% and 0.2% for (125)I and (103)Pd seeds, respectively, compared to average
      discrepancies for the original measured values of 4.8%. On average, the revised
      measured values are 4.3% and 5.9% lower than the original measured values for
      (103)Pd and (125)I seeds, respectively. The average of revised DRCs and Monte
      Carlo values is 3.8% and 2.8% lower for (125)I and (103)Pd seeds, respectively,
      than the consensus values in TG-43U1 or TG-43U1S1. CONCLUSIONS: This work shows
      that f(rel) is TLD shape and seed model dependent suggesting a need to update the
      generalized energy response dependence, i.e., relative absorbed-dose sensitivity,
      measured 25 years ago and applied often to DRC measurements of (125)I and (103)Pd
      brachytherapy seeds. The intrinsic energy dependence for LiF TLDs deduced here is
      consistent with previous dosimetry studies and emphasizes the need to revise the
      DRC consensus values reported by TG-43U1 or TG-43U1S1.

PMID- 25370678
TI  - OBLIGING SURGEONS TO ENHANCE: NEGLIGENCE LIABILITY FOR UNCORRECTED FATIGUE AND
      PROBLEMS WITH PROVING CAUSATION.
AB  - Increasing interest in the use of cognitive enhancing pharmaceuticals, such as
      modafinil, has led to considerable ethical debate about issues around
      authenticity, fairness and even whether there is a moral obligation to enhance.
      This latter question has raised questions as to whether there might be a legal
      obligation to enhance. We have argued elsewhere that the law will not oblige a
      professional to self-enhance. In this article, we explore a second reason why a
      claim of negligence for a failure to enhance would be unlikely to succeed: the
      problem of establishing causation. As the science on enhancers and what they are
      capable of currently stands, it would be almost invariably impossible to
      establish a causal link between failure to enhance to redress fatigue, and the
      harm that allegedly resulted. Even where a link between fatigue and harm can be
      established, it will be extremely difficult to show that taking an enhancer would
      have averted the harm. We focus on the most likely context in which such claims
      might arise--clinical negligence--and on the most efficacious enhancing drug
      currently available-modafinil.

PMID- 25370679
TI  - Clinical management for complications related to implantable LVAD use.
AB  - More than 250 continuous flow LVADs have been implanted in Japan during the last
      3 years, with 1-year survival rates of 90%. These excellent results cannot be
      achieved without VAD teams who know the detail of surgical techniques and
      perioperative management. Preoperative optimization of RV function is essential
      and intraoperative managements are focused on adequate balance between right and
      left ventricle to prevent right ventricular (RV) failure. For postoperative RV
      failure early institution of temporary RV mechanical support improves outcomes.
      Immediate CT scanning is crucial if LVAD patients complain of new neurological
      symptoms. When CT reveals cerebral hemorrhage, INR should be reduced as soon as
      possible. The driveline (DL) exit site remains a significant source of LVAD
      related infections, and orientation and immobilization of the DL is important.
      Although vacuum assisted closure is useful to facilitate drainage and healing in
      pump pocket as well as DL infections, urgent heart transplantation, bridging to
      recovery, or pump exchange may become the only options to eradicate LVAD-related
      infections. Patients with continuous flow LVAD are more prone to developing de
      novo aortic insufficiency. Although majority of them can be managed medically,
      some require surgical intervention. The cause of pump thrombosis is
      multifactorial, including lowered INR and pump speed, and implantation
      techniques. It is important to exchange pumps in a timely manner either through a
      median sternotomy or subcostal incision in highly suspected patients indicated by
      elevated LDH and left-sided heart failure.

PMID- 25370681
TI  - Comparative analysis of cervical cytology and human papillomavirus genotyping by
      three different methods in a routine diagnostic setting.
AB  - Application of Bethesda guidelines on cervical cytology involves human
      papillomavirus (HPV) determinations on all ASC-US and ASC-H results. We compared
      HPV DNA results in view of the eventual development of a cervical intraepithelial
      neoplasia lesion determined either on cytology or histology. A total of 214
      liquid-based cytology samples were analysed. Three different HPV DNA methods were
      applied: the Abbott RealTime High Risk HPV test, INNO-Lipa HPV Genotyping Extra
      and Full Spectrum PCR HPV Amplification and Detection/Genotyping System by
      Lab2Lab Diagnostic Service. A comparison of these three methods showed full
      concordance only for 49 samples (23%), and 27 (13%) of the samples were
      discordant in indicating the presence of the high-risk HPV type. Out of 214
      patients, 88 were selected who presented with a cervical intraepithelial
      neoplasia or a VAIN lesion at follow-up cytology or histology. In this group,
      full concordance with HPV genotyping was present only in 19 (22%) follow-up
      samples. Nine (10%) follow-up samples showed discordant results for the presence
      of a high-risk genotype between the three genotyping methods tested either by
      negativity for high-risk HPV by one of the methods (n=6) or by failure to
      genotype HPV (n=2), or by a combination of both (n=1). Moreover, discordance for
      the detection of HPV16 or HPV18 was observed between the three HPV DNA genotyping
      methods used in 9 (10%) follow-up samples. In addition, the performance of
      genotyping methods on 20 external quality samples was assessed, showing
      discordant results for HPV16 and HPV18. Major differences were found in the
      genotyping results according to the HPV DNA method. Our findings highlight the
      importance of careful interpretation of data from studies using different HPV
      genotyping methods and underline the need for standardization by method
      validation in clinical laboratories, especially in the setting of primary HPV
      screening. 

PMID- 25370682
TI  - Initial results of the National Colorectal Cancer Screening Program in Lithuania.
AB  - The aim of the present study was to review the National Colorectal Cancer
      Screening Program (the Program) in Lithuania according to the criteria set by the
      European Union. In Lithuania, screening services are provided free of charge to
      the population. The National Health Insurance Fund (NHIF) reimburses the
      institutions for performing each service; each procedure within the Program has
      its own administrative code. All the information about the performance of the
      Program is collected in one institution - the NHIF. The results of the Program
      were retrieved from the database of NHIF from the start of the Program from 1
      July 2009 to 1 July 2012. Descriptive analysis of epidemiological indicators was
      carried out. Results were compared with the references in the guidelines of the
      European Union for quality assurance in colorectal cancer (CRC) screening and
      diagnosis. Information service [which involves fecal immunochemical test (FIT)]
      was provided to 271,396 of 890,309 50-74-year-old residents. The screening uptake
      was 46.0% over 3 years. During this period, 19,455 (7.2%) FITs were positive and
      251,941 (92.8%) FITs were negative. Referral for colonoscopy was performed in
      10,190 (52.4%) patients. Colonoscopy was performed in 12,864 (66.1%) patients.
      Colonoscopy did not indicate any pathological findings in 8613 (67.0%) patients.
      Biopsies were performed in 4251 (33.0%) patients. The rate of high-grade
      neoplasia reported by pathologists was 3.9%; the rate of cancer was 3.1% of all
      colonoscopies. The rate of CRC detected by the Program was 0.2%. The CRC
      screening program in Lithuania meets most of the requirements for standardized
      CRC screening programs. The invitation coverage and rate of referral for
      colonoscopy after positive FIT should be improved.

PMID- 25370683
TI  - Tea consumption and the incidence of cancer: a systematic review and meta
      analysis of prospective observational studies.
AB  - The aim of this study was to summarize the current evidence on the strength of
      associations between tea consumption and the incidence of cancer at different
      sites. We searched PubMed, Embase and the Cochrane Library for relevant articles
      published before October 2013. Prospective studies that reported effect estimates
      of cancer incidence, with 95% confidence intervals (CIs), for more than two
      categories of tea consumption were included. We analysed 87 datasets (57
      articles), which included a total of 49,812 incident cases. Overall, high tea
      consumption had no significant effect on the risk of gastric, rectal, colon,
      lung, pancreatic, liver, breast, prostate, ovarian, bladder cancers or gliomas.
      However, high tea consumption was associated with a reduced risk of oral cancer
      (risk ratio 0.72; 95% CI 0.54-0.95; P=0.021). A dose-response meta-analysis
      suggested that an increase in tea consumption by one cup per day was associated
      with a reduced risk of oral cancer (risk ratio 0.89; 95% CI 0.80-0.98; P=0.022),
      but had little effect on the incidence of other cancers. Subgroup analysis
      indicated that an increase in the consumption of black tea by one cup per day was
      associated with an increased risk of breast cancer. Moreover, in western
      countries, we found that an increase in the consumption of tea by one cup per day
      was associated with a reduced risk of bladder cancer. Increased tea consumption
      has no significant effect on the risk of common malignancies. For some cancer
      types, associations differ according to sex, ethnicity and tea type.

PMID- 25370684
TI  - Fecal hemoglobin concentration as a measure of risk to tailor colorectal cancer
      screening: are we there yet?
AB  - The aim of this paper was to examine the distribution of fecal hemoglobin (f-Hb)
      concentration in a Spanish colorectal cancer screening population according to
      sociodemographic characteristics and analyze whether f-Hb was associated with
      clinical outcomes (type of lesion and its location). From September 2009 to
      November 2012, we sent 77,744 invitations to individuals aged 50-69 years to
      provide one sample of feces. f-Hb was measured on samples from 27,606 screenees
      (35.5%). Colonoscopy findings and pathology data were collected on the 1406
      screenees with f-Hb greater than 100 ng Hb/ml (20 mg Hb/g feces). The Mann
      Whitney U-test and the Kruskal-Wallis test were used to compare f-Hb (median)
      according to sociodemographic variables, clinical outcomes, and histological
      features of adenomas. f-Hb from greater than 100 ng Hb/ml was categorized into
      quartiles. Regression models were used to determine whether f-Hb was a risk
      predictor of colorectal lesions. f-Hb was associated directly with the severity
      of the colorectal lesions. An overlap between individuals with a negative
      colonoscopy and those with a low-risk adenoma was observed. High-grade dysplasia,
      villous histology, distal location, and increasing size were all features
      associated with an increased f-Hb level. f-Hb could be used in individual risk
      assessment to determine surveillance strategies for colorectal cancer screening.

PMID- 25370685
TI  - Mammographic density and risk of breast cancer in Korean women.
AB  - We carried out this study to evaluate the association between mammographic
      density adjusted for age and BMI and early-onset breast cancer in Asian women. We
      recruited 213 Korean patients with breast cancer (45% diagnosed before the age of
      50 years) and 630 controls matched for age, menopausal status, and examination
      date. The percentage and absolute size of dense areas on digital mammograms were
      measured using a computer-assisted thresholding technique (Cumulus). We carried
      out an analysis using the conditional logistic regression model with adjustment
      for covariates. An increase by 1 SD in age and BMI-adjusted absolute dense area
      and percentage dense area was associated with a 1.15-fold (95% confidence
      interval: 1.03, 1.29) and 1.20-fold (95% confidence interval: 1.06, 1.37)
      increased risk of breast cancer, respectively. These associations were stronger
      for premenopausal disease (P=0.07 and 0.01, respectively) and for disease
      diagnosed before age 50 (P=0.07 and 0.02, respectively) than for postmenopausal
      disease (P=0.16 and 0.23, respectively) or later onset disease (P=0.10 and 0.10,
      respectively). There was no difference in the associations with premenopausal
      versus postmenopausal and early-onset versus late-onset disease. After adjusting
      for age and BMI, both a greater absolute dense area and a greater percentage
      dense area were associated with an increased risk of breast cancer, particularly
      at a young age. 

PMID- 25370686
TI  - Are new supraglottic airway devices, tracheal tubes and airway viewing devices
      cost-effective?
AB  - Over the past two decades, a plethora of new airway devices has become available
      to the pediatric anesthetist. While all have the laudable intention of improving
      patient care and some have proven clinical benefits, these devices are often
      costly and at times claims of an advantage over current equipment and techniques
      are marginal. Supraglottic airway devices are used in the majority of pediatric
      anesthetics delivered in the U.K., and airway-viewing devices provide an
      alternative for routine intubation as well as an option in the management of the
      difficult airway. Yet hidden beneath the convenience of the former and the
      technology of the latter, the impact on basic airway skills with a facemask and
      the lack of opportunities to fine-tune the core skill of intubation represent an
      unrecognised and unquantifiable cost. A judgement on this value must be factored
      into the absolute purchase cost and any potential benefits to the quality of
      patient care, thus blurring any judgement on cost-effectiveness that we might
      have. An overall value on cost-effectiveness though not in strict monetary terms
      can then be ascribed. In this review, we evaluate the role of these devices in
      the care of the pediatric patient and attempt to balance the advantages they
      offer against the cost they incur, both financial and environmental, and in any
      quality improvement they might offer in clinical care.

PMID- 25370680
TI  - Palatogenesis and cutaneous repair: A two-headed coin.
AB  - BACKGROUND: The reparative mechanism that operates following post-natal cutaneous
      injury is a fundamental survival function that requires a well-orchestrated
      series of molecular and cellular events. At the end, the body will have closed
      the hole using processes like cellular proliferation, migration, differentiation
      and fusion. RESULTS: These processes are similar to those occurring during
      embryogenesis and tissue morphogenesis. Palatogenesis, the formation of the
      palate from two independent palatal shelves growing towards each other and
      fusing, intuitively, shares many similarities with the closure of a cutaneous
      wound from the two migrating epithelial fronts. CONCLUSIONS: In this review, we
      summarize the current information on cutaneous development, wound healing,
      palatogenesis and orofacial clefting and propose that orofacial clefting and
      wound healing are conserved processes that share common pathways and gene
      regulatory networks.

PMID- 25370687
TI  - Health professionals should do more to prevent children ending up in custody, BMA
      says.

PMID- 25370688
TI  - Synergistic protective effects of escin and low-dose glucocorticoids against
      vascular endothelial growth factor-induced blood-retinal barrier breakdown in
      retinal pigment epithelial and umbilical vein endothelial cells.
AB  - Previous studies have shown that escin possesses glucocorticoid (GC)-like anti
      edematous and anti-inflammatory effects. The present study was designed to
      investigate whether escin exhibits synergistic protective effects against blood
      retinal barrier (BRB) breakdown when combined with GC in an in vitro monolayer
      BRB model, based on retinal pigment epithelial (RPE) cells and human umbilical
      vein endothelial cells (HUVECs). The results showed that low concentrations of
      escin and triamcinolone acetonide (TA) administered separately did not affect BRB
      trans-endothelial (epithelium) resistance (TEER). However, when administered
      together, escin and TA significantly inhibited reduced BRB TEER following
      treatment with vascular endothelial growth factor (VEGF). Furthermore, low
      concentrations of escin and TA administered together significantly increased the
      expression levels of occludin and ZO-1. This demonstrates that escin and GC have
      synergistic protective effects against BRB breakdown, and the molecular
      mechanisms may be related to the upregulation of occludin and ZO-1 expression.
      The combination of escin with GC indicates a potential beneficial strategy for
      the treatment of breakdown of the BRB.

PMID- 25370689
TI  - Strained olefin enables triflic anhydride mediated direct dehydrative
      glycosylation.
AB  - For the first time, we demonstrated that Tf2O mediated direct dehydrative
      glycosylation was possible simply with strained olefins, and other typical bases
      were inhibitors of this reaction. We optimized the glycosylation conditions and
      found that typical benzyl protected 1-OH pyranosyl donors and certain alcohol
      acceptors were suitable for our glycosylation system. Furthermore, we found that
      complete 1,2-trans selectivity and a wider acceptor scope could be achieved with
      2-O-Bz 3,4,6-tri-O-Bn pyranosyl donors. 

PMID- 25370690
TI  - microRNA-34a and microRNA-34c promote the activation of human hepatic stellate
      cells by targeting peroxisome proliferator-activated receptor gamma.
AB  - Liver fibrosis is the common outcome of almost all cases of chronic liver
      disease. The hallmark of liver fibrosis is the activation of hepatic stellate
      cells (HSCs). microRNA-34a (miR-34a), which regulates a plethora of target
      proteins involved in the cell cycle, apoptosis, differentiation and cellular
      development, is found to be upregulated in both activated HSCs and liver
      fibrosis, while it is consistently downregulated in numerous cancer types. In the
      present study, the possible mechanisms underlying the role of miR-34a and miR-34c
      in the activation of the HSCs was investigated. Through bioinformatics analysis
      and a luciferase reporter assay, five genes were identified to be the target
      genes of miR-34a and miR-34c. Of these, peroxisome proliferator-activated
      receptor gamma (PPARgamma) was selected for further investigation. Mutation
      luciferase reporter assay confirmed the direct interaction of PPARgamma and miR
      34a and miR-34c. Western blot analysis and quantitative polymerase chain reaction
      demonstrated that the expression of PPARgamma was negatively correlated with the
      expression of miR-34a and miR-34c during the activation of HSCs. In activated
      human HSCs, inhibitors of miR-34a and miR-34c upregulated the expression of
      PPARgamma and downregulated the expression of alpha-smooth muscle actin. These
      data suggested that the miR-34 family may be involved the process of liver
      fibrosis by targeting PPARgamma.

PMID- 25370691
TI  - Dose tailoring of anti-tumour necrosis factor-alpha therapy delivers useful
      clinical efficacy in Crohn disease patients experiencing loss of response.
AB  - BACKGROUND: 'Dose tailoring' of anti-tumour necrosis factor alpha (TNF-alpha)
      therapy in Crohn disease (CD), by dose escalation, or shortening of dosing
      intervals, has been suggested to regain clinical response following a flare in a
      proportion of patients. However, reported outcome data are sparse and none exists
      from Australia. METHOD: In an observational multicentre, retrospective study, the
      impact of anti-TNF-alpha dose tailoring on corticosteroid use, the need for
      surgery and physician perception of clinical efficacy was examined in a real
      world setting at six Australian adult teaching hospitals. Demographics, disease
      characteristics, medications, indication for and duration of dose tailoring were
      documented. RESULTS: Fifty-five CD patients were identified as requiring dose
      tailoring and secondary loss of response was the indication in 96%. Either
      adalimumab (64%) or infliximab (36%) was dose escalated for a median of 5 months
      (range 1-47), with a median of 20 months follow up (range 3-65). At 3 months,
      dose tailoring reduced the mean number of days on high-dose corticosteroids (45
      vs 23, P = 0.01). Most (78%) patients remained resection free, and 73% of
      physicians reported good clinical efficacy of dose tailoring. Of those who de
      escalated therapy due to induction of remission, long-term (>12 months) follow up
      and complete data on steroid use were available in 15/28, with 12/15 (80%)
      remaining steroid free at 1 year. CONCLUSION: Short-term dose tailoring regains
      disease response in the majority of patients with CD. Of these, most will remain
      free of corticosteroids at 1 year after de-escalating therapy.

PMID- 25370692
TI  - Technique: DNA hairpins track traction.

PMID- 25370694
TI  - Copy number variants in attention-deficit hyperactive disorder: identification of
      the 15q13 deletion and its functional role.
AB  - OBJECTIVES: Evidence has supported a role for rare copy number variants in the
      etiology of attention-deficit hyperactivity disorder (ADHD), in particular, the
      region 15q13, which is also a hot spot for several neuropsychiatric disorders.
      This region spans several genes, but their role and the biological implications
      remain unclear. METHODS: We carried out, for the first time, an analysis of the
      15q13 region in an Italian cohort of 117 ADHD patients and 77 controls using the
      MLPA method, confirmed by a genome single-nucleotide polymorphism array. In
      addition, we probed for downstream effects of the 15q13 deletions on gene
      expression by carrying out a transcriptomic analysis in blood. RESULTS: We found
      15q13 deletions in two ADHD patients and identified 129 genes as significantly
      dysregulated in the blood of the two ADHD patients carrying 15q13 deletions
      compared with ADHD patients without 15q13 deletions. As expected, genes in the
      deleted region (KLF13, MTMR10) were downregulated in the two patients with
      deletions. Moreover, a pathway analysis identified apoptosis, oxidation
      reduction, and immune response as the mechanisms that were altered most
      significantly in the ADHD patients with 15q13 deletions. Interestingly, we showed
      that deletions in KLF13 and CHRNA7 influenced the expression of genes belonging
      to the same immune/inflammatory and oxidative stress signaling pathways.
      CONCLUSION: Our findings are consistent with the presence of 15q13 deletions in
      Italian ADHD patients. More interestingly, we show that pathways related to
      immune/inflammatory response and oxidative stress signaling are affected by the
      deletion of KFL13 and CHRNA7. Because the phenotypic effects of 15q13 are
      pleiotropic, our findings suggest that there are shared biologic pathways among
      multiple neuropsychiatric conditions.

PMID- 25370695
TI  - Gaucher disease with jawbone involvement: a case report.
AB  - INTRODUCTION: Gaucher disease is an autosomal recessive systemic condition, and
      the most common of the lysosomal storage disorders. It is characterized by lipid
      accumulation in certain cells and organs, particularly macrophages, which appear
      on light microscopy as 'Gaucher cells' or vacuolated lipid-laden
      reticuloendothelial cells. Long bone involvement is common in Gaucher disease,
      whereas craniofacial bone involvement is extremely rare. Reports confirming the
      diagnoses of Gaucher disease involving craniofacial bones by histopathologic
      evidence are even rarer. CASE PRESENTATION: A 46-year-old Caucasian Ashkenazi
      Jewish woman with Gaucher disease presented with jawbone pain and lytic
      radiographic lesions of her mandible. Surgical biopsy of a mandibular lesion
      revealed Gaucher cells infiltrating the mandible, which correlated with
      radiographic and clinical findings, supporting a diagnosis of Gaucher disease
      with jawbone involvement. CONCLUSIONS: Lysosomal storage diseases can have head
      and neck manifestations, and bone involvement in Gaucher disease is common.
      Therefore, careful consideration of signs and symptoms and medical history, with
      a thorough review of systems, is important when evaluating patients with
      lysosomal storage disorders to rule out head and neck involvement of disease.
      Biopsy may be warranted in some cases for more definitive diagnosis of painful
      jawbone lesions and to rule out other odontogenic and non-odontogenic conditions
      in the differential diagnosis.

PMID- 25370697
TI  - Structural and functional analysis of an asymmetric bidirectional promoter in
      Arabidopsis thaliana.
AB  - Bidirectional promoters are relatively abundant in eukaryotic genomes, suggesting
      that they have an important biological significance. As yet, few of these
      promoters have been characterized in detail. Here, using a promoter::GUS
      transgene approach has revealed that the intergenic region of Arabidopsis
      thaliana divergent genes At1g71850 and At1g71860 is an asymmetric bidirectional
      promoter, which exhibits an orientation-dependent expression profile. The
      strength of the forward promoter was greater than that of the reverse promoter,
      and their tissue specificities were not identical. Deletion analyses revealed
      that this bidirectional promoter could be divided into three functional regions.
      The basal level and tissue specificity of the promoter in the reverse orientation
      were regulated positively by region II and negatively by region III, whereas
      promoter activity in the forward orientation was regulated negatively by region
      II and positively by region I. Thus the 52-bp stretch of region II had a dual
      function, enhancing expression in the reverse orientation and suppressing it in
      the forward orientation. These results demonstrated that the activity of the
      At1g71850-At1g71860 bidirectional promoter was modulated by complex interactions
      between both positive and negative cis-acting elements. These findings will
      enhance our understanding of the regulatory mechanisms of plant bidirectional
      promoters. 

PMID- 25370693
TI  - Extracellular matrix assembly: a multiscale deconstruction.
AB  - The biochemical and biophysical properties of the extracellular matrix (ECM)
      dictate tissue-specific cell behaviour. The molecules that are associated with
      the ECM of each tissue, including collagens, proteoglycans, laminins and
      fibronectin, and the manner in which they are assembled determine the structure
      and the organization of the resultant ECM. The product is a specific ECM
      signature that is comprised of unique compositional and topographical features
      that both reflect and facilitate the functional requirements of the tissue. 

PMID- 25370696
TI  - Research on the efficacy of Celastrus Orbiculatus in suppressing TGF-beta1
      induced epithelial-mesenchymal transition by inhibiting HSP27 and TNF-alpha
      induced NF-kappa B/Snail signaling pathway in human gastric adenocarcinoma.
AB  - BACKGROUND: Celastrus orbiculatus has been used as a folk medicine in China for
      the treatment of many diseases. In the laboratory, the ethyl acetate extract of
      Celastrus orbiculatus (COE) displays a wide range of anticancer functions.
      However, the inhibition of the metastasis mechanism of COE in gastric cancer
      cells has not been investigated so far. METHODS: The present study was undertaken
      to determine if the anti-metastasis effect of COE was involved in inhibiting of
      epithelial-mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901
      cells. In vitro, a well-established experimental EMT model involving transforming
      growth factor beta1 (TGF-beta1) was applied. Viability, invasion and migration,
      protein and mRNA expression of tumor cells were analyzed by MTT assay, transwell
      assay, western blot and real-time PCR, respectively. The molecular targets of COE
      in SGC-7901 cells were investigated by two-dimensional gel electrophoresis (2-DE)
      and MALDI-TOF-TOF mass spectrometer. Overexpression of heat shock protein 27
      (HSP27) was performed by transfected with the recombinant retroviral expression
      plasmid. In vivo, the anti-metastasis mechanisms of COE in the peritoneal gastric
      cancer xenograft model was explored and the effect was tested. RESULTS: The non
      cytostatic concentrations of COE effectively inhibited TGF-beta1 induced EMT
      process in SGC-7901 cells, which is characterized by prevented morphological
      changes, increased E-cadherin expression and decreased Vimentin, N-cadherin
      expression. Moreover, COE inhibited invasion and migration induced by TGF-beta1.
      Using a comparative proteomics approach, four proteins were identified as
      differently expressed, with HSP27 protein being one of the most significantly
      down-regulated proteins induced by COE. Moreover, the activation of nuclear
      factor kappaB (NF-kappaB)/Snail signaling pathway induced by tumor necrosis
      factor-alpha (TNF-alpha) was also attenuated under the pretreatment of COE.
      Interestingly, overexpression of HSP27 significantly decreases the inhibitory
      effect of COE on EMT and the NF-kappaB/Snail pathway. Furthermore, COE
      significantly reduced the number of peritoneal metastatic nodules in the
      peritoneal gastric cancer xenograft model. CONCLUSIONS: Taken together, these
      results suggest that COE inhibits the EMT by suppressing the expression of HSP27,
      correlating with inhibition of NF-kappaB/Snail signal pathways in SGC-7901 cells.
      Based on these results, COE may be considered a novel anti-cancer agent for the
      treatment of metastasis in gastric cancer.

PMID- 25370698
TI  - Smokers' sensory beliefs mediate the relation between smoking a light/low tar
      cigarette and perceptions of harm.
AB  - BACKGROUND: The sensory belief that 'light/low tar' cigarettes are smoother can
      also influence the belief that 'light/low tar' cigarettes are less harmful.
      However, the 'light' concept is one of several factors influencing beliefs. No
      studies have examined the impact of the sensory belief about one's own brand of
      cigarettes on perceptions of harm. OBJECTIVE: The current study examines whether
      a smoker's sensory belief that their brand is smoother is associated with the
      belief that their brand is less harmful and whether sensory beliefs mediate the
      relation between smoking a 'light/low tar' cigarette and relative perceptions of
      harm among smokers in China. METHODS: Data are from 5209 smokers who were
      recruited using a stratified multistage sampling design and participated in Wave
      3 of the International Tobacco Control (ITC) China Survey, a face-to-face survey
      of adult smokers and non-smokers in seven cities. RESULTS: Smokers who agreed
      that their brand of cigarettes was smoother were significantly more likely to say
      that their brand of cigarettes was less harmful (p<0.001, OR=6.86, 95% CI 5.64 to
      8.33). Mediational analyses using the bootstrapping procedure indicated that both
      the direct effect of 'light/low tar' cigarette smokers on the belief that their
      cigarettes are less harmful (b=0.24, bootstrapped bias corrected 95% CI 0.13 to
      0.34, p<0.001) and the indirect effect via their belief that their cigarettes are
      smoother were significant (b=0.32, bootstrapped bias-corrected 95% CI 0.28 to
      0.37, p<0.001), suggesting that the mediation was partial. CONCLUSIONS: These
      results demonstrate the importance of implementing tobacco control policies that
      address the impact that cigarette design and marketing can have in capitalising
      on the smoker's natural associations between smoother sensations and lowered
      perceptions of harm.

PMID- 25370700
TI  - Two-coordinate iron(I) complex [Fe{N(SiMe3)2}2](-) : synthesis, properties, and
      redox activity.
AB  - First-row two-coordinate complexes are attracting much interest. Herein, we
      report the high-yield isolation of the linear two-coordinate iron(I) complex salt
      [K(L)][Fe{N(SiMe3 )2 }2 ] (L=18-crown-6 or crypt-222) through the reduction of
      either [Fe{N(SiMe3 )2 }2 ] or its three-coordinate phosphine adduct [Fe{N(SiMe3
      )2 }2 (PCy3 )]. Detailed characterization is gained through X-ray diffraction,
      variable-temperature NMR spectroscopy, and magnetic susceptibility studies. One-
      and two-electron oxidation through reaction with I2 is further found to afford
      the corresponding iodo iron(II) and diiodo iron(III) complexes. 

PMID- 25370699
TI  - The density of tobacco retailers in home and school environments and relationship
      with adolescent smoking behaviours in Scotland.
AB  - BACKGROUND: Neighbourhood retailing of tobacco products has been implicated in
      affecting smoking prevalence rates. Long-term smoking usually begins in
      adolescence and tobacco control strategies have often focused on regulating
      'child spaces', such as areas in proximity to schools. This cross-sectional study
      examines the association between adolescent smoking behaviour and tobacco retail
      outlet density around home and school environments in Scotland. METHODS: Data
      detailing the geographic location of every outlet registered to sell tobacco
      products in Scotland were acquired from the Scottish Tobacco Retailers Register
      and used to create a retail outlet density measure for every postcode. This
      measure was joined to individual responses of the Scottish Schools Adolescent
      Lifestyle and Substance Use Survey (n=20 446). Using logistic regression models,
      we explored the association between the density of retailers, around both home
      and school address, and smoking behaviours. RESULTS: Those living in the areas of
      highest density of retailers around the home environment had 53% higher odds of
      reporting having ever smoked (95% CI 1.27 to 1.85, p<0.001) and 47% higher odds
      of reporting current smoking (95% CI 1.13 to 1.91 p<0.01). Conversely, those
      attending schools in areas of highest retail density had lower odds of having
      ever smoked (OR 0.66, 95% CI 0.50 to 0.86 p<0.01) and lower odds of current
      smoking (OR 0.75, 95% CI 0.59 to 0.95, p<0.05). CONCLUSIONS: The density of
      tobacco retail outlets in residential neighbourhoods is associated with increased
      odds of both ever smoked and current smoking among adolescents in Scotland.
      Policymakers may be advised to focus on reducing the overall density of tobacco
      outlets, rather than concentrating on 'child spaces'.

PMID- 25370701
TI  - Availability, need for, and use of work accommodations and benefits: are they
      related to employment outcomes in people with arthritis?
AB  - OBJECTIVE: To examine the availability, need, and use of workplace policies for
      workers with osteoarthritis (OA) and inflammatory arthritis (IA) and their
      association with employment outcomes. METHODS: Participants (n = 219) were
      employed, ages >=25 years, and diagnosed with OA or IA. They were recruited
      through community advertising and rheumatology clinics in 2 Canadian provinces.
      Respondents completed a 35-45-minute telephone interview assessing demographics
      (age, sex), health (diagnosis, pain, activity limitations), work context (job
      control), employment outcomes (workplace activity limitations, absenteeism,
      productivity losses, reduced hours), benefits (extended health, short-term
      leaves), and accommodations (flexible hours, modified schedules, special
      equipment/adaptations, work-at-home arrangements). Regression analyses examined
      differences in benefit/accommodation need and use. RESULTS: Many participants
      reported that arthritis impacted their work. But with the exception of extended
      health benefits, ~50-65% of participants reported not needing each individual
      benefit/accommodation, although only 7.3% of respondents reported needing no
      benefits or accommodations at all. Greater job control and education were
      associated with greater perceived need and use of benefits/accommodations. Need
      was also associated with greater activity limitations, and disclosure of
      arthritis was related to use of benefits/accommodations. Participants needing but
      not using workplace policies often had significantly poorer employment outcomes
      compared to those using benefits/accommodations. CONCLUSION: Findings are
      relevant to workers with arthritis and to employers. Results suggest that
      individuals with arthritis are unlikely to be a drain on workplace resources.
      Many individuals do not use benefits/accommodations until needed, and among those
      using them, there were generally positive relationships with diverse employment
      outcomes.

PMID- 25370702
TI  - Abnormal rib count in scoliosis surgery: impact on the reporting of spinal fusion
      levels.
AB  - PURPOSE: Variation in rib numbering has been noted in adolescent idiopathic
      scoliosis (AIS), but its effect on the reporting of fusion levels has not been
      studied. We hypothesized that vertebral numbering variations can lead to
      differing documentation of fusion levels. METHODS: We examined the radiographs of
      161 surgical AIS patients and 179 control patients without scoliosis. For AIS
      patients, the operative report of fusion levels was compared to conventional
      vertebral labeling from the first thoracic level and proceeding caudal. We
      defined normal counts as 12 thoracic (rib-bearing) and five lumbar (non-rib
      bearing) vertebrae. We compared our counts with data from 181 anatomic specimens.
      RESULTS: Among AIS patients, 22 (14 %) had an abnormal number of ribs and 29 (18
      %) had either abnormal rib or lumbar count. In 12/29 (41 %) patients, the
      operative report differed from conventional labeling by one level, versus 3/132
      (2 %) patients with normal numbering (p < 0.001). However, there were no cases
      seen of wrong fusion levels based on curve pattern. Among controls, 11 % had
      abnormal rib count (p = 0.41) compared to the rate in AIS. Anatomic specimen data
      did not differ in abnormal rib count (p = 1.0) or thoracolumbar pattern (p =
      0.59). CONCLUSIONS: The rate of numerical variations in the thoracolumbar
      vertebrae of AIS patients is equivalent to that in the general population. When
      variations in rib count are present, differences in numbering levels can occur.
      In the treatment of scoliosis, no wrong fusion levels were noted. However, for
      both scoliosis patients and the general population, we suggest adherence to
      conventional labeling to enhance clarity.

PMID- 25370703
TI  - Evaluation of a new protocol for sterility controls of corneal culture medium.
AB  - Careful testing for microbial contamination is essential for corneal transplants.
      Sterility tests are performed on the antibiotics containing culture medium
      leaving the problem that antibiotics might compromise the test results. In this
      study a protocol for the application of the automated BacT/Alert system for
      sterility testing of corneal cell culture medium was examined. Corneal culture
      medium in combination with an antibiotics degrading enzyme were injected in resin
      containing test bottles of the BacT/Alert system named FA plus (intended for
      aerobic microorganisms) or FN plus (intended for anaerobic microorganisms)
      depending on their aerobic or anaerobic nature. Additionally i-FA plus(aerobic
      test bottle for industrial use) bottles were used. Microbial test strains on the
      basis of the European Pharmacopaea (Staphylococcus aureus, Pseudomonas
      aeruginosa, Bacillus subtilis, Candida albicans, Aspergillus brasiliensis and
      Clostridium sporogenes) with the addition of Propioniobacterium acnes were added
      to the test bottles. The bottles were incubated at two different temperatures for
      14 days. The time to detection (TTD) was monitored for each bottle. Growth of the
      test strains except European Pharm was detected in the FA and FN Plus bottles.
      The TTD for the strains was 44 +/- 1.5 h (P. aeruginosa), 57.7 +/- 2.2 h (B.
      subtilis), 56 +/- 1 h (S. aureus), 26.3 +/- 1 h (C. sporogenes), 223 +/- 4.6 h
      (P. acnes), 64.4 +/- 10 (C. albicans). A. brasiliensis was detected in i-FA Plus
      bottles with a TTD of 94.9 +/- 3.7 h. The application of BacT/Alert FA Plus and
      FN Plus resin bottles in combination with a penicillin degrading enzyme is able
      to detect small scale microbial contamination with different microorganisms in
      antibiotic containing corneal culture medium. For detection of Aspergillus
      brasiliensis in the medium the (i-) FA Plus bottles should be used.

PMID- 25370704
TI  - Firm maternal parenting associated with decreased risk of excessive snacking in
      overweight children.
AB  - OBJECTIVE: To examine the relationship between parent feeding practices
      (restriction, monitoring, pressure to eat), general parenting behaviors
      (acceptance, psychological control, firm control), and aberrant child eating
      behaviors (emotional eating and excessive snacking) among overweight and normal
      weight children. METHODS: Overweight and normal weight children between 8 and 12
      years old and their mothers (n = 79, parent-child dyads) participated in this
      study. Mothers completed surveys on parent feeding practices (Child Feeding
      Questionnaire) and child eating behaviors (Family Eating and Activity Habits
      Questionnaire). Children reported on their mothers' general parenting behaviors
      (Child Report of Parent Behavior Inventory). Parent and child height and weight
      were measured and demographic characteristics assessed. Logistic regression
      models, stratified by child weight status and adjusting for parent BMI, were used
      to determine which parenting dimensions and feeding practices were associated
      with child emotional eating and snacking behavior. RESULTS: Overweight children
      displayed significantly more emotional eating and excessive snacking behavior
      than normal weight children. Mothers of overweight children used more restrictive
      feeding practices and psychological control. Restrictive feeding practices were
      associated with emotional eating in the overweight group (OR = 1.26, 95 % CI,
      1.02, 1.56) and excessive snacking behavior in the normal weight group (OR =
      1.13, 95 % CI, 1.01, 1.26). When examining general parenting, firm control was
      associated with decreased odds of excessive snacking in the overweight group (OR
      = 0.51, 95 % CI, 0.28, 0.93). CONCLUSION: Restrictive feeding practices were
      associated with aberrant child eating behaviors in both normal weight and
      overweight children. Firm general parenting however, was associated with
      decreased snacking behavior among overweight children. Longitudinal studies
      following children from infancy are needed to better understand the direction of
      these relationships.

PMID- 25370705
TI  - Classification of tumor area using combined DCE and DSC MRI in patients with
      glioblastoma.
AB  - This study proposes an automatic method for identification and quantification of
      different tissue components: the non-enhanced infiltrative tumor, vasogenic edema
      and enhanced tumor areas, at the subject level, in patients with glioblastoma
      (GB) based on dynamic contrast enhancement (DCE) and dynamic susceptibility
      contrast (DSC) MRI. Nineteen MR data sets, obtained from 12 patients with GB,
      were included. Seven patients were scanned before and 8 weeks following
      bevacizumab initiation. Segmentation of the tumor area was performed based on the
      temporal data of DCE and DSC at the group-level using k-means algorithm, and
      further at the subject-level using support vector machines algorithm. The
      obtained components were associated to different tissues types based on their
      temporal characteristics, calculated perfusion and permeability values and MR
      spectroscopy. The method enabled the segmentation of the tumor area into the
      enhancing permeable component; the non-enhancing hypoperfused component,
      associated with vasogenic edema; and the non-enhancing hyperperfused component,
      associated with infiltrative tumor. Good agreement was obtained between the group
      level, unsupervised and subject-level, supervised classification results, with
      significant correlation (r = 0.93, p < 0.001) and average symmetric root-mean
      square surface distance of 2.5 +/- 5.1 mm. Longitudinal changes in the volumes of
      the three components were assessed alongside therapy. Tumor area segmentation
      using DCE and DSC can be used to differentiate between vasogenic edema and
      infiltrative tumors in patients with GB, which is of major clinical importance in
      therapy response assessment.

PMID- 25370706
TI  - Expert-validated CSF segmentation of MNI atlas enhances accuracy of virtual
      glioma growth patterns.
AB  - Biomathematical modeling of glioma growth has been developed to optimize
      treatments delivery and to evaluate their efficacy. Simulations currently make
      use of anatomical knowledge from standard MRI atlases. For example, cerebrospinal
      fluid (CSF) spaces are obtained by automatic thresholding of the MNI atlas,
      leading to an approximate representation of real anatomy. To correct such
      inaccuracies, an expert-revised CSF segmentation map of the MNI atlas was built.
      Several virtual glioma growth patterns of different locations were generated,
      with and without using the expert-revised version of the MNI atlas. The adequacy
      between virtual and radiologically observed growth patterns was clearly higher
      when simulations were based on the expert-revised atlas. This work emphasizes the
      need for close collaboration between clinicians and researchers in the field of
      brain tumor modeling. 

PMID- 25370707
TI  - Lack of evidence for PlGF mediating the tumor resistance after anti-angiogenic
      therapy in malignant gliomas.
AB  - Placenta growth factor (PlGF) is a member of vascular endothelial growth factor
      family which can promote cancer growth by various mechanisms. Placenta growth
      factor is upregulated in many neoplastic diseases and serum levels of PlGF are
      increased in cancer patients following anti-angiogenic therapy. However, its role
      in glioma growth is yet not fully elucidated. In this study we analyzed the
      expression of PlGF mRNA using real time PCR in human gliomas of different WHO
      grades. Placenta growth factor mRNA levels were highly variable and did not
      correlate with WHO grades, arguing against a significant role in glioma
      progression. The highest PlGF expression was observed in anaplastic astrocytomas
      whereas grade II astrocytomas and glioblastomas displayed lower levels of
      expression. Immunohistochemical analysis showed that PlGF was expressed by
      inflammatory and endothelial cells in addition to tumor cells. Placenta growth
      factor mRNA expression in 12 matched glioblastoma samples before and after
      therapy, including bevacizumab and cilengitide treatment was largely unaffected
      by the aforementioned treatment modalities. In vitro, the exposure of VEGFR-1
      expressing glioma cells to bevacizumab did not increase the expression levels of
      PlGF mRNA. In summary, our results do not support the hypothesis that PlGF plays
      a major role in the resistance of gliomas after anti-angiogenic therapy. 

PMID- 25370708
TI  - Subspecialty surveillance of long-term course of small and moderate muscular
      ventricular septal defect: heterogenous practices, low yield.
AB  - BACKGROUND: No expert consensus guides practice for intensity of ongoing
      pediatric cardiology surveillance of hemodynamically insignificant small and
      moderate muscular ventricular septal defect (mVSD). Therefore, despite the well
      established benign natural history of mVSD, there is potential for widely
      divergent follow up practices. The purpose of this investigation was to evaluate
      (1) variations in follow up of mVSD within an academic children's hospital based
      pediatric cardiology practice, and (2) the frequency of active medical or
      surgical management resulting from follow up of mVSD. METHODS: We retrospectively
      reviewed records of 600 patients with isolated mVSD echocardiographically
      diagnosed between 2006 and 2012. Large mVSD were excluded (n = 4). Patient age,
      gender, echocardiographic findings, provider, recommendations for follow up, and
      medical and surgical management were tabulated at initial and follow up visits.
      Independent associations with follow up recommendations were sought using
      multivariate analysis. RESULTS: Initial echocardiography showed small single mVSD
      in 509 (85%), multiple small mVSD in 60 (10%), and small-to-moderate or moderate
      single mVSD in 31 (5%). The mean age at diagnosis was 15.9 months (0-18.5 years)
      and 25.7 months (0-18.5 years) at last follow up. There was slight female
      predominance (56.3%). Fourteen pediatric cardiology providers recommended 316
      follow up visits, 259 of which were actually accomplished. There were 37 other
      unplanned follow up visits. No medical or surgical management changes were
      associated with any of the follow up visits. The proportion of patients for whom
      follow up was advised varied among providers from 11 to 100%. Independent
      associations with recommendation for follow up were limited to the identity and
      clinical volume of the provider, age of the patient, and the presence of
      multiple, small-to-moderate, or moderate mVSD. CONCLUSIONS: In this large series
      of moderate or smaller mVSD, pediatric cardiology follow up was commonly
      recommended but resulted in no active medical or surgical management. Major
      provider based inconsistency in intensity of follow up of mVSD was identified,
      but is difficult to justify.

PMID- 25370709
TI  - The effects of bisphosphonate on the remodeling of different irregular bones in
      mice.
AB  - BACKGROUND: We aimed to compare the effects of bisphosphonate on the remodeling
      of irregular bones (the jaw and ilium) in mice after trauma. METHODS: To verify
      the feasibility of modeling osteonecrosis, 20 mice were injected
      intraperitoneally with zoledronate and dexamethasone (ZOL&DEX group),
      dexamethasone (DEX group), or phosphate-buffered saline (PBS) [control (CTR)
      group]. Mice then underwent extraction of the right maxillary first molar and
      creation of an artificial bony cavity in the ilium. Bone sections were stained
      with H&E for morphological studies. To further compare differences between the
      maxilla and the ilium caused by similar traumas, 80 mice were injected
      intraperitoneally with ZOL&DEX or PBS. Pathological progression at the injury
      sites was assessed at 1 day and at 1, 3, and 8 weeks after trauma using micro
      computed tomography (CT), H&E and immunohistochemistry analyses, high-performance
      liquid chromatography-mass spectrometry, and enzyme-linked immunosorbent assay.
      RESULTS: Only the ZOL&DEX model group effectively developed osteonecrosis. Bony
      sequestra, osseous sclerosis, unhealed mucosa, and radiopaque alveolar bone were
      found in the maxilla. In the ilium, there was a lower frequency of osteonecrotic
      disease and osseous sclerosis, and less suppression of bone remodeling than in
      the maxilla following long-term bisphosphonate administration. Zoledronate levels
      were higher in the maxilla. ZOL&DEX treatment suppressed the levels of RANKL and
      IL-17, but induced an upregulation of osteoprotegerin and FAM20C in both bones.
      CONCLUSION: Accumulation of bisphosphonate may increase the incidence of
      osteonecrosis. The RANKL/OPG pathway and IL-17 and FAM20C cytokines play key
      roles in the progression of pathologically abnormal bone remodeling.

PMID- 25370710
TI  - Recentralizing healthcare through evidence-based guidelines - striving for
      national equity in Sweden.
AB  - BACKGROUND: The Swedish government has increasingly begun to rely on so called
      informative governance when regulating healthcare. The question this article sets
      out to answer is: considered to be "the backbone" of the Swedish state's strategy
      for informative governance in healthcare, what kind of regulatory arrangement is
      the evidence-based National Guidelines? Together with national medical registries
      and an extensive system of quality and efficiency indicators, the National
      Guidelines constitutes Sweden's quality management system. METHODS: A framework
      for evaluating and comparing regulatory arrangements was used. It asks for
      instance: what is the purpose of the regulation and are regulation methods
      oriented towards deterrence or compliance? RESULTS: The Swedish National
      Guidelines is a regulatory arrangement intended to govern the prioritizations of
      all decision makers - politicians and administrators in the self-governing county
      councils as well as healthcare professionals - through a compliance model backed
      up by top-down benchmarking and built-in mechanisms for monitoring. It is thus an
      instrument for the central state to steer local political authorities. The
      purpose is to achieve equitable and cost-effective healthcare. CONCLUSIONS: This
      article suggests that the use of evidence-based guidelines in Swedish healthcare
      should be seen in the light of Sweden's constitutional setting, with several
      autonomous levels of political authority negotiating the scope for their decision
      making power. As decision-making capacity is relocated to the central government 
      from the democratically elected county councils responsible for financing and
      provision of healthcare - the Swedish National Guidelines is part of an ongoing
      process of healthcare recentralization in Sweden, reducing the scope for local
      decision-making. This represents a new aspect of evidence-based medicine (EBM)
      and clinical practice guidelines (CPGs).

PMID- 25370711
TI  - Annual report of the Committee on Gynecologic Oncology, the Japan Society of
      Obstetrics and Gynecology.
AB  - The Japan Society of Obstetrics and Gynecology collects and analyzes annual data
      on gynecologic cancers from member institutions. Here we present the Patient
      Annual Report for 2012 and the Treatment Annual Report for 2006. Data on 7028
      patients with cervical cancer, 8217 with endometrial cancer, 5140 with ovarian
      cancer and 1725 with ovarian borderline tumor for whom treatment was initiated in
      2012 were summarized in the Patient Annual Report. Data on the prognosis of 2699
      patients with cervical cancer, 3243 with endometrial cancer and 1898 with ovarian
      cancer for whom treatment was initiated in 2006 were analyzed in the Treatment
      Annual Report. In the Patient Annual Report for 2012, stage I accounted for
      55.4%, stage II for 23.0%, stage III for 11.0% and stage IV for 10.6% of all
      patients with cervical cancer. Stage I accounted for 72.2%, stage II for 7.0%,
      stage III for 13.4% and stage IV for 7.3% of all patients with endometrial
      cancer. Stage I accounted for 43.1%, stage II for 9.2%, stage III for 29.7% and
      stage IV for 7.2% of all patients with ovarian cancer. In the Treatment Annual
      Report for 2006, the 5-year overall survival rates for patients with cervical
      cancer were 92.9% for stage I, 74.6% for stage II, 55.3% for stage III and 24.3%
      for stage IV. The equivalent rates for patients with endometrial cancer were
      96.3%, 92.7%, 80.6% and 35.8%, respectively; and those for patients with ovarian
      surface epithelial-stromal tumors were 90.6%, 82.9%, 48.7% and 40.9%,
      respectively. 

PMID- 25370712
TI  - Social capital, socioeconomic status, and health-related quality of life among
      older adults in Bogota (Colombia).
AB  - OBJECTIVE: The main goal of this study was to evaluate the relationship between
      levels of cognitive social capital and health-related quality of life (HRQOL).
      METHODS: A multilevel, cross-sectional study was conducted in 2007 in Bogota
      Colombia. A total of 1,907 older adults completed the Spanish version of the
      Short Form of Health Survey (SF-8) to assess HRQOL. Cognitive dimension of social
      capital was assessed. Hierarchical linear regressions were conducted to determine
      the associations between social capital variables and HRQOL. RESULTS: Only 20% to
      25% of the population reported trust in others and shared values. A total of 93%
      percent reported that people in their neighborhood would try to take advantage of
      them if given a chance. Higher social capital indicators were positively
      associated with the mental and physical dimensions of HRQOL. DISCUSSION: Results
      from this study support evidence on the disintegration of the Colombian society,
      which may be influenced by high levels of social inequality.

PMID- 25370713
TI  - Depression and Its Associated Factors in Older Indians: A Study Based on Study of
      Global Aging and Adult Health (SAGE)-2007.
AB  - OBJECTIVE: To estimate the prevalence of depression and determine the factors
      associated with it in older Indians aged 50 years and above. METHOD: This study
      was based on a nationally representative sample of 7,150 older Indians from WHO's
      Study of Global Aging and Adult Health, SAGE-2007. Mild, moderate, and severe
      depression was assessed through International Classification of Diseases, 10th
      revision, Diagnostic Criteria for Research (ICD-10-DCR). Logistic regression
      analysis was used to assess the impact of socio-demographic, health, and diet
      related characteristics on depression. RESULTS: Estimated prevalence of mild,
      moderate, and severe depression in the past 12 months was 13.6%, 12.4%, and 8.2%
      respectively, in older Indians. Functional disability, cognitive impairment, low
      quality of life, low wealth status, and chronic conditions such as angina,
      asthma, or chronic lung disease were the significant (p < .05 or .1) risk factors
      for depression. DISCUSSION: Protective and risk factors identified can be helpful
      in formulation of different policies for older Indians.

PMID- 25370714
TI  - Multiangle dynamic light scattering for the improvement of multimodal particle
      size distribution measurements.
AB  - Dynamic Light Scattering (DLS) is a widely used technique for measuring the size
      distributions of nano- and micro-particles dispersed in a liquid. The principle
      is based on the analysis of the temporal fluctuations of light scattered by the
      particles at a given scattering angle. However, single-angle DLS measurements may
      lack resolution and robustness, particularly for multimodal and/or polydisperse
      samples. Multi-angle Dynamic Light Scattering (MDLS) provides more robust,
      reproducible and accurate Particle Size Distributions (PSDs) than single-angle
      DLS. In this paper, a novel inversion method based on Bayesian inference is
      proposed for the estimation of the number PSD from MDLS measurements. The
      efficiency and robustness of this method is demonstrated through simulated and
      real data. 

PMID- 25370715
TI  - Identification of Leishmania donovani peroxin 14 residues required for binding
      the peroxin 5 receptor proteins.
AB  - Trafficking of peroxisomal targeting signal 1 (PTS1) proteins to the Leishmania
      glycosome is dependent on the docking of the LdPEX5 receptor to LdPEX14 on the
      glycosomal membrane. A combination of deletion and random mutagenesis was used to
      identify residues in the LdPEX14 N-terminal region that are critical for
      mediating the LdPEX5-LdPEX14 interaction. These studies highlighted residues 35
      75 on ldpex14 as the core domain required for binding LdPEX5. Single point
      mutation within this core domain generally did not affect the ldpex5-(203-391)
      ldpex14-(1-120) interaction; notable exceptions were substitutions at Phe40,
      Val46 or Phe57 which completely abolished or increased the apparent Kd value for
      ldpex5-(203-391) binding 30-fold. Biochemical studies revealed that these point
      mutations did not alter either the secondary or quaternary structure of LdPEX14
      and indicated that the latter residues were critical for stabilizing the LdPEX5
      LdPEX14 interaction. 

PMID- 25370716
TI  - Comparative local immunogenic potential of scaffolds prepared from porcine
      cholecyst, jejunum, and urinary bladder in rat subcutaneous model.
AB  - Extracellular matrices isolated from several mammalian organs/tissues have found
      several clinical uses as xenografts or implants. However, they may cause
      complications because of adverse immunologic reactions. Scaffolds that promote
      favorable graft-acceptance reaction are preferred for fabricating xenografts. The
      objective of this study was to evaluate the immunogenic potential of a porcine
      cholecyst-derived scaffold (CDS), prepared by a non-detergent/enzymatic method,
      in comparison with jejunum and urinary bladder-derived scaffolds in a rat
      subcutaneous model. Key graft-rejection/acceptance reaction was evaluated at the
      site of implantation by studying the occurrence and/or function of
      immunocompetent cells in the tissue reaction. There was differential occurrence
      of M1-macrophage, M2-macrophage, T-helper cells, T-cytotoxic cells, B-cells, and
      mast cells in the tissue reaction and the CDS attracted few cells compared with
      other scaffolds. Real-time polymerase chain reaction for evaluating mRNA of
      functional markers like inducible nitric oxide synthase (M1 macrophage), arginase
      1 (M2 macrophage), interferon gamma (TH1 lymphocytes), and interlukin-4 (TH2
      lymphocytes) suggested that the CDS, compared with the scaffolds prepared from
      small intestine and urinary bladder, elicited M2 macrophage and TH2 lymphocyte
      polarization that are congenial graft-acceptance reactions. The results indicated
      that CDS has less immunogenic potential compared with the scaffolds prepared from
      jejunum and urinary bladder when used as subcutaneous graft in rats. It was
      concluded that CDS is a promising animal-derived xenograft for biomedical
      application.

PMID- 25370717
TI  - In situ observation and enhancement of leaflet tissue formation in bioprosthetic
      "biovalve".
AB  - Biovalves, autologous tri-leaflet valved conduits, are formed in the subcutaneous
      spaces of animals. The valves are formed using molds encapsulated with autologous
      connective tissues. However, tissue migration into the small apertures in the
      molds for leaflet formation is generally slower than that for conduit formation
      around the molds. In this study, the formation of the leaflet tissues was
      directly and non-invasively observed using a wireless capsule endoscope. The
      molds were assembled from 6 parts, one of which was impregnated with the
      endoscope, and embedded into subcutaneous pouches in goats (n = 30). Tissue
      ingrowth into the apertures gradually occurred from the edges of the leaflet
      parts. Tissue formation was accompanied by capillary formation. At 63.1 +/- 17.1
      days after embedding, the apertures were completely replaced with autologous
      connective tissue, forming the leaflet tissues. Leaflet formation was enhanced by
      including fat tissue (46.7 +/- 4.2 days) or blood (41.1 +/- 6.9 days) in the
      apertures before embedding. The creation of slit openings, in conjunction with
      addition of blood to the apertures, further enhanced leaflet formation (37.0 +/-
      2.8 days). Since leaflet formation could be observed endoscopically, the
      appropriate embedding period for complete biovalve formation could be determined.

PMID- 25370718
TI  - Hemodynamic changes during left ventricular assist device-off test correlate with
      the degree of cardiac fibrosis and predict the outcome after device explantation.
AB  - Myocardial recovery occurs in a small cohort of patients receiving left
      ventricular assist device (LVAD) support, but identification of candidates for
      device removal remains challenging. We hypothesized that hemodynamic evaluation
      using echocardiography and right heart catheter during temporary suspension of
      LVAD support (LVAD-off test) can assess cardiac recovery to predict successful
      device removal. To prove this hypothesis, we reviewed 44 patients who underwent
      LVAD-off test from January 2000 to March 2011 at Osaka University Hospital.
      Twenty-two of them underwent LVAD explant, 9 showed sustaining recovery
      (successful explant, SE-group); whereas 13 had a recurrent heart failure (failed
      explant, FE-group). The other 22 patients remained LVAD dependent (nonrecovery,
      NR-group). Echocardiography showed significant lower ejection fraction (LVEF) in
      NR-group than in SE- and FE-group after termination of LVAD support, but there
      was no difference between SE- and FE-group. On the other hand, elevation in
      pulmonary capillary wedge pressure (DeltaPCWP) was significantly smaller in SE
      group than in FE- and NR-groups. The degree of cardiac fibrosis significantly
      increased in FE- and NR-group during the LVAD support, while it did not increase
      in SE-group. The degree of cardiac fibrosis at the time of LVAD explantation
      correlated significantly with PCWP at LVAD halt and DeltaPCWP, and it had
      significant impact on the outcome after LVAD weaning. In conclusion, the data
      obtained during LVAD-off test using echocardiography and right heart catheter
      significantly correlated with the degree of cardiac fibrosis at the time of LVAD
      explantation. LVAD-off test is a useful method to predict the successful LVAD
      explantation. 

PMID- 25370719
TI  - Minimally invasive implantation of an extracorporeal membrane oxygenation circuit
      used as a temporary left ventricular assist device: a new concept for bridging to
      permanent cardiac support.
AB  - The implantation of cardiac assist devices is associated with poor outcome in
      patients with multiple organ failure and unknown neurologic status. Therefore,
      temporary left ventricular assist devices (LVAD) using, for example,
      extracorporeal centrifugal pumps may provide the chance to further evaluate the
      patient's clinical course and a potential qualification for implantable LVAD
      therapy. On the other hand, a main disadvantage of the temporary LVAD
      implantation is the need for redo surgery, increasing the risk of the final LVAD
      Implantation. To minimize this drawback of the temporary LVAD implantation, we
      implanted the temporary LVAD using a minimally invasive technique. The operation
      was done without cardiopulmonary bypass support, and the temporary LVAD was
      implanted through upper hemisternotomy and left anterior mini-thoracotomy. The
      patient recovered from multiple organ failure and was successfully bridged to a
      permanent LVAD therapy. 

PMID- 25370720
TI  - Is high socioeconomic status a risk factor for multiple sclerosis? A systematic
      review.
AB  - High socioeconomic status (SES) is generally associated with better health
      outcomes, but some research has linked it with an increased risk of multiple
      sclerosis (MS). The evidence for this association is inconsistent and has not
      previously been systematically reviewed. A systematic review of cohort and case
      control studies in any language was conducted looking at the association between
      MS and SES. MEDLINE and EMBASE were searched for articles in all languages
      published up until 23 August 2013. Twenty-one studies from 13 countries were
      included in the review. Heterogeneity of study settings precluded carrying out a
      meta-analysis, and a qualitative synthesis was performed instead. Five studies,
      all from more unequal countries, reported an association between high SES and MS.
      Thirteen studies reported no evidence of an association, and three studies
      reported an association with low SES. These 16 studies largely came from more
      egalitarian countries. The evidence for an association between high SES and
      increased MS risk is inconsistent but with some indication of a stronger effect
      in countries and time periods with higher inequality. Firm conclusions are
      hampered by the failure of most studies to control for other important risk
      factors for MS. 

PMID- 25370721
TI  - Immunosuppression as a possible cofactor of occupational skin cancer in an
      outdoor worker.

PMID- 25370722
TI  - Relationship between tumour necrosis factor-related apoptosis inducing ligand
      (TRAIL) and vascular endothelial growth factor in human multiple myeloma
      patients.
AB  - Tumour necrosis factor-alfa (TNF-alpha) is an inflammatory cytokine with a wide
      spectrum of biological activity, including angiogenesis. Tumour necrosis factor
      related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of
      proteins, plays a role in the regulation of vascular responses, but its effect on
      the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL
      concentrations in parallel with pro-angiogenic cytokines in serum and their
      expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and
      24 healthy volunteers. The study showed statistically higher concentrations of
      TRAIL and TNF-alpha, as well as of VEGF and its receptor, in MM patients compared
      to healthy volunteers and patients in advanced stages of the disease.
      Furthermore, we observed a significant decrease in all studied pro-angiogenic
      cytokines and significant increase of TRAIL concentration after anti-angiogenic
      therapy, with meaningful differences between responders (at least partial
      remission) and patients with progression during the induction treatment. It was
      also established that TRAIL correlated statistically and negatively with pro
      angiogenic cytokines such as VEGF with its receptor and expression of VEGF and
      syndecan-1 in TB. In summary, our data indicate that in MM patients, both
      clinical course and treatment responsiveness are associated with dynamic yet
      corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such
      as VEGF with its receptor and expression of VEGF and syndecan-1 in TB.

PMID- 25370723
TI  - Reversal of Immunoglobulin A Deficiency in Children.
AB  - PURPOSE: Immunoglobulin A deficiency (IgAD) is the most common primary
      immunodeficiency in the general population. It is defined as a serum IgA level
      below or equal to 0.07 g/l with normal IgM and IgG levels in children over the
      age of 4. However, a few cases of reversal of IgAD at later ages have been
      observed previously, especially in pediatric patients. This study aimed at
      investigating the frequency of reversal in a large cohort of children and young
      adults in order to evaluate the present definition of IgAD. METHODS: Clinical
      laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age,
      were retrieved from five university hospitals in Sweden. Follow up in the
      children where IgA serum levels had been routinely measured was subsequently
      performed. In addition, follow up of the IgA-levels was also performed at 4, 8
      and 16 years of age in children who were IgA deficient at the age of 4 years in a
      Swedish population-based birth cohort study in Stockholm (BAMSE). RESULTS: Nine
      out of 39 (23.1%) children who were identified as IgAD at 4 years of age
      subsequently increased their serum IgA level above 0.07 g/L. The average age of
      reversal was 9.53 +/- 2.91 years. In addition, 30 out of the 131 (22.9%) children
      with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum
      IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at
      4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of
      age) where 4 were normalized their serum IgA levels while 4 still showed low
      serum levels of IgA, yet above the level defining IgAD. The results indicate that
      using 4 years of age, as a cut off for a diagnosis of IgAD may not be
      appropriate. CONCLUSIONS: Our findings suggest that a diagnosis of IgAD should
      not be made before the early teens using 0.07 g/L of IgA in serum as a cut off.

PMID- 25370724
TI  - Apathy in untreated early-stage Parkinson disease: relationship with other non
      motor symptoms.
AB  - Apathy is a frequent and disabling behavioral disorder in patients with
      Parkinson's disease (PD). Its prevalence in treatment-naive patients with early
      stage PD has not been extensively investigated. Moreover, whether apathy is
      related to other non-motor symptoms in early-stage PD is unknown. Our objective
      was to determine the prevalence and features of apathy and associated factors in
      a group of treatment-naive patients with early-stage PD. Ninety-five treatment
      naive patients with early-stage PD participated in the study. Apathy, depression,
      motor symptoms, and overall cognitive efficiency were assessed. The presence of
      the main non-motor symptoms was checked during a detailed clinical interview.
      Group comparisons were carried out to investigate the association with apathy.
      Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter
      had concomitant depression. Apathetic patients had significantly more severe
      motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non
      apathetic patients. When considering non-motor symptoms, apathy was significantly
      associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which
      were more prevalent in apathetic patients than in non-apathetic patients. In
      treatment-naive patients with early-stage PD, apathy was significantly associated
      with more severe motor symptoms and a lower cognitive status. After adjustment
      for these factors, apathy appeared to be a relatively isolated, independent
      symptom because the only other associated non-motor symptoms were fatigue and
      anhedonia.

PMID- 25370725
TI  - Triclosan Resistance in a Bacterial Fish Pathogen, Aeromonas salmonicida subsp.
      salmonicida, is Mediated by an Enoyl Reductase, FabV.
AB  - Triclosan, the widely used biocide, specifically targets enoyl-acyl carrier
      protein reductase (ENR) in the bacterial fatty acid synthesis system. Although
      the fish pathogen Aeromonas salmonicida subsp. salmonicida exhibits triclosan
      resistance, the nature of this resistance has not been elucidated. Here, we aimed
      to characterize the triclosan resistance of A. salmonicida subsp. salmonicida
      causing furunculosis. The fosmid library of triclosan-resistant A. salmonicida
      subsp. salmonicida was constructed to select a fosmid clone showing triclosan
      resistance. With the fosmid clone showing triclosan resistance, a subsequent
      secondary library search resulted in the selection of subclone pTSR-1. DNA
      sequence analysis of pTSR-1 revealed the presence of a chromosomal-borne fabV
      encoding ENR homolog. The ENR of A. salmonicida (FabVas) exhibited significant
      homology with previously known FabV, including the catalytic domain YX(8)K.
      fabVas introduction into E. coli dramatically increased its resistance to
      triclosan. Heterologous expression of FabVas might functionally replace the
      triclosan-sensitive FabI in vivo to confer E. coli with triclosan resistance. A
      genome-wide search for fabVas homologs revealed the presence of an additional
      fabV gene (fabVas2) paralog in A. salmonicida strains and the fabVas orthologs
      from other gram-negative fish pathogens. Both of the potential FabV ENRs
      expressed similarly with or without triclosan supplement. This is the first
      report about the presence of two potential FabV ENRs in a single pathogenic
      bacterium. Our result suggests that triclosan-resistant ENRs are widely
      distributed in various bacteria in nature, and the wide use of this biocide can
      spread these triclosan-tolerant ENRs among fish pathogens and other pathogenic
      bacteria.

PMID- 25370726
TI  - Effects of antibiotic growth promoter and characterization of ecological
      succession in Swine gut microbiota.
AB  - Ever since the ban on antibiotic growth promoters (AGPs), the livestock death
      rate has increased owing to pathogenic bacterial infections. There is a need of
      developing AGP alternatives; however, the mechanisms by which AGP enhances
      livestock growth performance are not clearly understood. In this study, we fed 3
      week-old swine for 9 weeks with and without AGPs containing chlortetracycline,
      sulfathiazole, and penicillin to investigate the effects of AGPs on swine gut
      microbiota. Microbial community analysis was done based on bacterial 16S rRNA
      genes using MiSeq. The use of AGP showed no growth promoting effect, but
      inhibited the growth of potential pathogens during the early growth stage. Our
      results showed the significant increase in species richness after the
      stabilization of gut microbiota during the post-weaning period (4-week-old).
      Moreover, the swine gut microbiota was divided into four clusters based on the
      distribution of operational taxonomic units, which was significantly correlated
      to the swine weight regardless of AGP treatments. Taxonomic abundance analysis
      indicated a negative correlation between host weight and the abundance of the
      family Prevotellaceae species, but showed positive correlation to the abundance
      of the family Spirochaetaceae, Clostridiaceae_1, and Peptostreptococcaeae
      species. Although no growth performance enhancement was observed, the use of AGP
      inhibited the potential pathogens in the early growth stage of swine. In
      addition, our results indicated the ecological succession of swine gut microbiota
      according to swine weight. Here, we present a characterization of swine gut
      microbiota with respect to the effects of AGPs on growth performance.

PMID- 25370727
TI  - The Epitope Recognized by Monoclonal Antibody 2B6 in the B/C Domains of Classical
      Swine Fever Virus Glycoprotein E2 Affects Viral Binding to Hyperimmune Sera and
      Replication.
AB  - Classical swine fever (CSF) is a highly contagious disease of pigs caused by CSF
      virus (CSFV). E2 is the major viral envelope protein of immune dominance that
      induces neutralizing antibodies and confers protection against CSFV infection.
      The B/C domains of E2 are variable among CSFV isolates, which could affect
      immunogenicity and binding to antibodies. We attempted to characterize the
      epitope recognized by a monoclonal antibody 2B6 (mAb-2B6) raised against the E2
      B/C domains of the vaccine C-strain and to examine if mutations in the epitope
      region would affect antibody binding and viral neutralization. The epitope
      specific for mAb-2B6 recognition is linear, spanning five residues
      (774)DGXNP(778) in the B/C domains. The residue N777 is indispensable for the
      specificity. The epitope exists only in group 1 strains, but not in those of
      group 2. The recombinant viruses containing individual mutations on the epitope
      region lost the reactivity to mAb-2B6. The mutant virus RecC-N777S had low
      replication potential, about 10-fold decrease in the yield of progeny virus
      particles, whereas the mutant virus RecC-P778A reverted to proline upon
      continuous passaging. The mutations on the mAb-2B6 epitope region did not affect
      neutralization by anti-C-strain polyclonal sera from pigs. Deletion from aa774
      covering the mAb-2B6 epitope, but not that from aa781, also affected binding with
      the polyclonal antibodies from vaccinated pigs, although the major binding region
      for the vaccinated antibodies is aa690-773. 

PMID- 25370728
TI  - Production, Structural Elucidation, and In Vitro Antitumor Activity of  Trehalose
      Lipid Biosurfactant from Nocardia farcinica Strain.
AB  - The objective of this study was to isolate and identify the chemical structure of
      a biosurfactant produced by Nocardia farcinica strain BN26 isolated from soil,
      and evaluate its in vitro antitumor activity on a panel of human cancer cell
      lines. Strain BN26 was found to produce glycolipid biosurfactant on n-hexadecane
      as the sole carbon source. The biosurfactant was purified using medium-pressure
      liquid chromatography and characterized as trehalose lipid tetraester (THL) by
      nuclear magnetic resonance spectroscopy and mass spectrometry. Subsequently, the
      cytotoxic effects of THL on cancer cell lines BV-173, KE-37 (SKW-3), HL-60, HL
      60/DOX, and JMSU-1 were evaluated by MTT assay. It was shown that THL exerted
      concentration-dependent antiproliferative activity against the human tumor cell
      lines and mediated cell death by the induction of partial oligonucleosomal DNA
      fragmentation. These findings suggest that THL could be of potential to apply in
      biomedicine as a therapeutic agent.

PMID- 25370729
TI  - Integration of BpMADS4 on various linkage groups improves the utilization of the
      rapid cycle breeding system in apple.
AB  - Rapid cycle breeding in apple is a new approach for the rapid introgression of
      agronomically relevant traits (e.g. disease resistances) from wild apple species
      into domestic apple cultivars (Malus * domestica Borkh.). This technique
      drastically shortens the long-lasting juvenile phase of apple. The utilization of
      early-flowering apple lines overexpressing the BpMADS4 gene of the European
      silver birch (Betula pendula Roth.) in hybridization resulted in one breeding
      cycle per year. Aiming for the selection of non-transgenic null segregants at the
      end of the breeding process, the flower-inducing transgene and the gene of
      interest (e.g. resistance gene) that will be introgressed by hybridization need
      to be located on different chromosomes. To improve the flexibility of the
      existing approach in apple, this study was focused on the development and
      characterization of eleven additional BpMADS4 overexpressing lines of four
      different apple cultivars. In nine lines, the flowering gene was mapped to
      different linkage groups. The differences in introgressed T-DNA sequences and
      plant genome deletions post-transformation highlighted the unique molecular
      character of each line. However, transgenic lines demonstrated no significant
      differences in flower organ development and pollen functionality compared with
      non-transgenic plants. Hybridization studies using pollen from the fire blight
      resistant wild species accession Malus fusca MAL0045 and the apple scab-resistant
      cultivar 'Regia' indicated that BpMADS4 introgression had no significant effect
      on the breeding value of each transgenic line. 

PMID- 25370730
TI  - A one-step-ahead pseudo-DIC for comparison of Bayesian state-space models.
AB  - In the context of state-space modeling, conventional usage of the deviance
      information criterion (DIC) evaluates the ability of the model to predict an
      observation at time t given the underlying state at time t. Motivated by the
      failure of conventional DIC to clearly choose between competing multivariate
      nonlinear Bayesian state-space models for coho salmon population dynamics, and
      the computational challenge of alternatives, this work proposes a one-step-ahead
      DIC, DICp, where prediction is conditional on the state at the previous time
      point. Simulations revealed that DICp worked well for choosing between state
      space models with different process or observation equations. In contrast,
      conventional DIC could be grossly misleading, with a strong preference for the
      wrong model. This can be explained by its failure to account for inflated
      estimates of process error arising from the model mis-specification. DICp is not
      based on a true conditional likelihood, but is shown to have interpretation as a
      pseudo-DIC in which the compensatory behavior of the inflated process errors is
      eliminated. It can be easily calculated using the DIC monitors within popular
      BUGS software when the process and observation equations are conjugate. The
      improved performance of DICp is demonstrated by application to the multi-stage
      modeling of coho salmon abundance in Lobster Creek, Oregon. 

PMID- 25370732
TI  - Urostomy and health-related quality of life in patients with lower urinary tract
      dysfunction.
AB  - OBJECTIVE: Urinary diversion may be an option in patients with disabling lower
      urinary tract dysfunction (DLUTD), refractory to conservative and minor invasive
      treatment. The aim of this study was to evaluate whether urostomy improves
      quality of life and cost of surgery, in terms of complications, loss of kidney
      function and hospital stay, in these patients. MATERIAL AND METHODS: This
      prospective study included 52 consecutive patients (nine men and 43 women) with
      various benign disorders. Twenty-six patients received an ileal conduit and 26 a
      continent cutaneous diversion. The patients completed the general health-related
      quality of life instrument WHOQOL-BREF and a urinary problem-specific quality of
      life instrument preoperatively and 6 and 12 months after surgery. Length of
      hospital stay and complications were registered. Intravenous urography and
      determination of glomerular filtration rate (GFR) were performed preoperatively
      and 12 months postoperatively. RESULTS: Disease-specific and health-related
      quality of life improved significantly (p < 0.0005 and p < 0.05) in all domains
      except for social relationship, from preoperative to 12 months after surgery.
      There was no difference in improvement between patients with continent and those
      with incontinent diversion. Mean hospital stay was 14 days. Early and late
      complications required open surgery in 12 patients (23%). GFR was unchanged
      postoperatively. CONCLUSIONS: Urinary diversion improves health-related and
      disease-specific quality of life in patients with DLUTD refractory to
      conservative and minor invasive treatments. The burden of surgery is acceptable.
      Urinary diversion could be recommended more often in such patients.

PMID- 25370731
TI  - Azathioprine is more effective than mesalazine at preventing recurrent bowel
      obstruction in patients with ileocecal Crohn's disease.
AB  - BACKGROUND: Patients with subocclusive Crohn's disease (CD) who received
      azathioprine (AZA) therapy had lower re-hospitalization rates due to all causes
      and for surgical management of CD compared to those treated with mesalazine
      during a 3-year period. We investigated whether AZA also was effective for
      prevention of recurrent bowel obstruction. MATERIAL/METHODS: Rates of recurrent
      bowel occlusion were compared between patients treated with AZA and those treated
      with mesalazine. We assessed the time interval-off intestinal obstruction as well
      as the occlusion-free survival for both groups. RESULTS: There was a
      significantly lower cumulative rate of patients with recurrent subocclusion in
      the AZA group (56%) compared with the mesalazine group (79%; OR 3.34, 95% CI 1.67
      8.6; P=0.003), with the number needed to treat in order to prevent 1 subocclusion
      episode of 3.7 favoring AZA. The occlusion-free time interval was longer in the
      AZA group compared with the mesalazine group (28.8 vs. 18.3 months; P=0.000). The
      occlusion-free survival at 12, 24, and 36 months was significantly higher in the
      AZA group (91%, 81%, and 72%, respectively) than in the mesalazine group (64.7%,
      35.3%, and 23.5%, respectively; P<0.05 for all comparisons). CONCLUSIONS: In an
      exploratory analysis of patients with subocclusive ileocecal CD, maintenance
      therapy with AZA is more effective than mesalazine for eliminating or postponing
      recurrent intestinal obstruction during 3 years of therapy.

PMID- 25370733
TI  - MicroRNA-146a rs2910164 polymorphism and the risk of diffuse large B cell
      lymphoma in the Chinese Han population.
AB  - The aim of this study was to determine the association of the microRNA-146a (miR
      146a) polymorphism with the risk of diffuse large B cell lymphoma (DLBCL). The
      genotyping of miR-146a rs2910164 polymorphism was detected by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed
      that CC genotype and C alleles distribution in the DLBCL patient was
      significantly higher than that of the controls (p = 0.01 and p = 0.01,
      respectively). No significant differences were found between the two subgroups
      when stratified by clinical characteristics including sexual, age at admission,
      performance status, pathological type, Ann Arbor stage, LDH and beta2-MG value.
      The miR-146a expression was detected by the Taqman real-time PCR. The result
      showed that the miR-146a expression was notably upregulated in DLBCL patients
      when compared with controls (p = 0.02). In addition, the miR-146a expression of
      CC genotypes subgroup was drastically downregulated than that of GC/GG genotype
      subgroup in DLBCL patients (p = 0.0003), suggesting that this polymorphism can
      functionally affect the expression of miR-146a. In conclusion, it was shown that
      the miR-146a rs2910164 polymorphism is associated with the risk of DLBCL in the
      Chinese Han population.

PMID- 25370734
TI  - The close correlation between heparanase and COX-2 expression in
      lymphangiogenesis of cervical cancer.
AB  - Recent observations indicate the vital role of heparanase in tumor
      lymphangiogenesis. Moreover, heparanase is involved in angiogenesis in esophageal
      cancer through induction of COX-2. However, it is unclear whether heparanase is
      also associated with COX-2 in lymphangiogenesis of cervical cancer. In this
      study, heparanase, COX-2 and VEGF-C expression were examined in 80 cervical
      cancer cases by immunohistochemical staining. We also studied the correlation of
      heparanase and COX-2 expression with lymphangiogenesis of cervical cancer
      quantified as lymphatic vessel density. Our results showed that expressions of
      heparanase and COX-2 were associated with lymphangiogenesis of cervical cancer.
      Furthermore, a significant correlation was found between the expression of
      heparanase and COX-2 (P < 0.0001). Heparanase is positively correlated with
      expressions of COX-2 and VEGF-C. These findings revealed that heparanase may play
      important function in lymphangiogenesis of cervical cancer via the regulation of
      COX-2 expression.

PMID- 25370735
TI  - A difficulty in improving population survival outcome of gastric cancer in
      mainland China: low proportion of early diseases.

PMID- 25370737
TI  - New bipolar host materials for realizing blue phosphorescent organic light
      emitting diodes with high efficiency at 1000 cd/m2.
AB  - New host molecules such as 9-(6-(9H-carbazol-9-yl)pyridin-3-yl)-6-(9H-carbazol-9
      yl)-9H-pyrido[2,3-b]indole (pPCB2CZ) and 9-(6-(9H-carbazol-9-yl)pyridin-2-yl)-6
      (9H-carbazol-9-yl)-9H-pyrido[2,3-b]indole (mPCB2CZ) were designed and synthesized
      for blue phosphorescent organic light-emitting diodes (PhOLEDs). The glass
      transition temperatures of two host molecules were measured higher than 120 
      degrees C, and the identical triplet energies were determined to be 2.92 eV for
      both molecules. The bis(3,5-difluoro-2-(2-pyridyl)phenyl-(2
      carboxypyridyl)iridium(III) (FIrpic)-doped mPCB2CZ-based PhOLED exhibited
      practically useful driving voltage of 4.8 V in a simple organic three layer
      device configuration which has a smaller number of interfaces in conventional
      multilayer PhOLEDs. Also, the high quantum efficiency of 23.7% is reported at the
      practically useful brightness value of 1000 cd/m2.

PMID- 25370736
TI  - Intrapersonal, social and physical environmental determinants of moderate-to
      vigorous physical activity in working-age women: a systematic review protocol.
AB  - BACKGROUND: The majority of North American adult females do not meet current
      physical activity recommendations (150 min of moderate-to-vigorous intensity
      physical activity (MVPA) per week accrued in >=10 min bouts) ultimately placing
      themselves at increased risk of morbidity and mortality. Working-age females face
      particular challenges in meeting physical activity recommendations as they have
      multiple demands, including occupational, family and social demands. To develop
      effective interventions to increase MVPA among working-age females, it is
      necessary to identify and understand the strongest modifiable determinants
      influencing these behaviours. Therefore, the objective of this systematic review
      is to examine the available evidence to identify intrapersonal, social and
      environmental determinants of MVPA among working-age females. METHODS/DESIGN: Six
      electronic databases will be searched to identify all prospective cohort studies
      that report on intrapersonal, social and/or environmental determinants of MVPA in
      working-age females. Grey literature sources including theses, published
      conference abstracts and websites from relevant organizations will also be
      included. Articles that report on intrapersonal (e.g. health status, self
      efficacy, socio-economic status (SES), stress, depression), social environmental
      (e.g. crime, safety, area SES, social support, climate and capital, policies),
      and environmental (e.g. weather, workplace, home, neighbourhood, recreation
      environment, active transportation) determinants of MVPA in a working-age (mean
      age 18-65 years) female population will be included. Risk of bias will be
      assessed within and across all included studies using the Tool to Assess Risk of
      Bias in Cohort Studies and the Grades of Recommendation, Assessment, Development
      and Evaluation approach. Harvest plots will be used to synthesize results across
      all determinants, and meta-analyses will be conducted where possible among
      studies with sufficient homogeneity. DISCUSSION: This review will provide a
      comprehensive examination of evidence in this field and will serve to highlight
      gaps for future research on the determinants of MVPA in working-age females and
      ultimately inform intervention design. SYSTEMATIC REVIEW REGISTRATION PROSPERO:
      CRD42014009750.

PMID- 25370738
TI  - A tissue specific magnetic resonance contrast agent, Gd-AMH, for diagnosis of
      stromal endometriosis lesions: a phase I study.
AB  - The anti-mullerian hormone (AMH) is a homodimeric glycoprotein member of the
      transforming growth factor beta (TGF-beta) superfamily, is secreted by Sertoli
      cells in the embryonic testes and is responsible of the regression of the
      mullerian duct. The physiological functions of this protein remain largely
      unknown, and its expression in human tissues has yet to be completely determined.
      Firstly, we analyzed AMH expression in human tissues by immunohistochemistry. AMH
      was distributed in many organs, although with different tissue and cell
      localization and various expression levels; we also demonstrated strong AMH
      expression in endometriosis tissues. Secondly, we demonstrated the ability of an
      anti-AMH antibody, labeled with gadiolinium, to be directly detected by magnetic
      resonance in small endometriosis lesions (5 mm in diameter) in vivo in a mouse
      model. In conclusion, our data suggest that based on its expression pattern, AMH
      may serve to maintain physiological cellular homeostasis in different human
      tissues and organs. Moreover, it is strongly expressed in endometriosis lesions
      as a selective tissue specific contrast agent for in vivo detection of stromal
      endometriosis lesions. The potential significance of these findings could be
      further validated in a clinical setting.

PMID- 25370739
TI  - Hexane cracking over steamed phosphated zeolite H-ZSM-5: promotional effect on
      catalyst performance and stability.
AB  - The nature behind the promotional effect of phosphorus on the catalytic
      performance and hydrothermal stability of zeolite H-ZSM-5 has been studied using
      a combination of (27) Al and (31) P MAS NMR spectroscopy, soft X-ray absorption
      tomography and n-hexane catalytic cracking, complemented with NH3 temperature
      programmed desorption and N2 physisorption. Phosphated H-ZSM-5 retains more acid
      sites and catalytic cracking activity after steam treatment than its non
      phosphated counterpart, while the selectivity towards propylene is improved. It
      was established that the stabilization effect is twofold. First, the local
      framework silico-aluminophosphate (SAPO) interfaces, which form after
      phosphatation, are not affected by steam and hold aluminum atoms fixed in the
      zeolite lattice, preserving the pore structure of zeolite H-ZSM-5. Second, the
      four-coordinate framework aluminum can be forced into a reversible sixfold
      coordination by phosphate. These species remain stationary in the framework under
      hydrothermal conditions as well. Removal of physically coordinated phosphate
      after steam-treatment leads to an increase in the number of strong acid sites and
      increased catalytic activity. We propose that the improved selectivity towards
      propylene during catalytic cracking can be attributed to local SAPO interfaces
      located at channel intersections, where they act as impediments in the formation
      of bulky carbenium ions and therefore suppress the bimolecular cracking
      mechanism. 

PMID- 25370740
TI  - Salt-enabled visual detection of DNA.
AB  - We report herein a label-free, salt-enabled visual detection strategy for DNA,
      based on the alteration of surface adhesion properties of salt solution, which
      can translate to the change in the size of the salt residue upon drying, with
      self-assembled DNA nanostructures. This environmentally friendly array assay
      protocol enables the achievement of a detection sensitivity comparable to classic
      colorimetric methods, single-base mismatch differentiation selectivity, multiple
      target detection capability, RNA target detection, and a ligase chain reaction
      rolling circle amplification implementation format. 

PMID- 25370741
TI  - The impact of organisational factors on horizontal bullying and turnover
      intentions in the nursing workplace.
AB  - AIM: To examine the impact of organisational factors on bullying among peers
      (i.e. horizontal) and its effect on turnover intentions among Canadian registered
      nurses (RNs). BACKGROUND: Bullying among nurses is an international problem. Few
      studies have examined factors specific to nursing work environments that may
      increase exposure to bullying. METHODS: An Australian model of nurse bullying was
      tested among Canadian registered nurse coworkers using a web-based survey (n =
      103). Three factors - misuse of organisational processes/procedures,
      organisational tolerance and reward of bullying, and informal organisational
      alliances - were examined as predictors of horizontal bullying, which in turn was
      examined as a predictor of turnover intentions. The construct validity of model
      measures was explored. RESULTS: Informal organisational alliances and misuse of
      organisational processes/procedures predicted increased horizontal bullying that,
      in turn, predicted increased turnover intentions. Construct validity of model
      measures was supported. CONCLUSION: Negative informal alliances and misuse of
      organisational processes are antecedents to bullying, which adversely affects
      employment relationship stability. IMPLICATIONS FOR NURSING MANAGEMENT: The
      results suggest that reforming flawed organisational processes that contribute to
      registered nurses' bullying experiences may help to reduce chronically high
      turnover. Nurse leaders and managers need to create workplace processes that
      foster positive networks, fairness and respect through more transparent and
      accountable practices.

PMID- 25370742
TI  - The 9-homocubyl cation rearrangement revisited.
AB  - Complexity of the potential energy surface of the 9-homocubyl cation is revealed
      by Born-Oppenheimer molecular dynamics simulations and high ab initio levels. The
      stereospecific automerizations observed experimentally involve bridged ions,
      which have either an aromatic or an anti-aromatic character. New pathways leading
      to more stable isomers are unveiled. 

PMID- 25370743
TI  - Inhibitory effect of emodin on migration, invasion and metastasis of human breast
      cancer MDA-MB-231 cells in vitro and in vivo.
AB  - In breast cancer, metastasis is the main reason for patient mortality. In the
      present study, we used breast cancer MDA-MB-231 cells and a mouse xenograft model
      to demonstrate the effect of emodin on the migration, invasion and metastasis of
      human breast cancer MDA-MB-231 cells and the related mechanisms. In vitro, wound
      healing and Transwell assays showed that emodin dose-dependently inhibited the
      migration and invasion of MDA-MB-231 cells. Enzyme-linked immunosorbent assay
      (ELISA) showed that emodin decreased the secretion of MMP-2 and MMP-9. Western
      blot analysis showed that emodin downregulated the expression levels of MMP-2,
      MMP-9, uPA and uPAR as well as p38 inhibitor SB203580 and ERK inhibitor PD980559,
      even though TIMP-1 and TIMP-2 were not obviously changed in the MDA-MB-231 cells.
      Furthermore, emodin inhibited the activity of p38 and ERK1/2 in the MDA-MB-231
      cells. In vivo, emodin inhibited lung metastasis in mice bearing the breast
      cancer MDA-MB-231 xenografts with no obvious changes in body weight, liver and
      kidney functions. These results indicated that emodin inhibited the lung
      metastasis of human breast cancer in a mouse xenograft model, and inhibited the
      invasion of MDA-MB-231 cells associated with the downregulation of MMP-2, MMP-9,
      uPA and uPAR expression as well as decreased activity of p38 and ERK.

PMID- 25370744
TI  - A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma
      susceptibility.
AB  - ARF is a small, highly basic protein that can be induced by oncogenic stimuli and
      exerts growth-inhibitory and tumour-suppressive activities through the activation
      of p53. Here we show that, in human melanocytes, ARF is cytoplasmic,
      constitutively expressed, and required for maintaining low steady-state levels of
      superoxide under conditions of mitochondrial dysfunction. This mitochondrial
      activity of ARF is independent of its known autophagic and p53-dependent
      functions, and involves the evolutionarily conserved acidic motif GHDDGQ, which
      exhibits weak homology to BCL-2 homology 3 (BH3) domains and mediates interaction
      with BCL-xL--an important regulator of mitochondrial redox homeostasis. Melanoma
      predisposing CDKN2A germline mutations, which affect conserved glycine and
      aspartate residues within the GHDDGQ motif, impair the ability of ARF to control
      superoxide production and suppress growth of melanoma cells in vivo. These
      results reveal an important cell-protective function of ARF that links
      mitochondrial dysfunction and susceptibility to melanoma.

PMID- 25370745
TI  - HIF-1 signaling pathway involving iNOS, COX-2 and caspase-9 mediates the
      neuroprotection provided by erythropoietin in the retina of chronic ocular
      hypertension rats.
AB  - This study aimed to investigate the impacts of erythropoietin (EPO) on the
      electroretinogram b-wave (ERG-b), and on the mRNA and protein expression levels
      of hypoxia-inducible factor-1alpha (HIF-1alpha), inducible nitric oxide synthase
      (iNOS), cyclooxygenase-2 (COX-2) and caspase-9 in chronic ocular hypertension
      rats. Episcleral vein cauterization (EVC) was used to establish the chronic
      ocular hypertension rat model based on the intraocular pressure (IOP) value. ERG
      b and mRNA and protein expression levels of HIF-1alpha, iNOS, COX-2 and caspase-9
      in normal, EVC-treated and EVC combined with EPO (EVC+EPO)-treated rats were
      measured by electroretinography, RT-PCR and western blotting, respectively.
      Moreover, the correlations of HIF-1alpha with IOP, ERG-b, iNOS, COX-2 and caspase
      9 were evaluated. The mRNA and protein expression levels of HIF-1alpha, iNOS, COX
      2 and caspase-9 in EVC-treated rats were increased significantly compared with
      normal rats. The peak expression levels of HIF-1alpha, iNOS, COX-2 and caspase-9
      were respectively obtained 7, 7, 7 and 14 days postoperatively. Compared with EVC
      treated rats, EPO administration weakened the mRNA and protein expression levels
      of HIF-1alpha, iNOS, COX-2 and caspase-9. The mRNA expression level of HIF-1alpha
      demonstrated a significant positive correlation with IOP and ERG-b. HIF-1alpha
      was positively correlated with iNOS, COX-2 and caspase-9 at the mRNA and protein
      levels. The protective effect of EPO on the retina of chronic ocular hypertension
      rats may be mediated by the HIF-1 signaling pathway involving iNOS, COX-2 and
      caspase-9.

PMID- 25370746
TI  - Gaze behaviour when monitoring pain faces: An eye-tracking study.
AB  - BACKGROUND: The vigilance-(attentional) avoidance hypothesis (VAH) developed for
      explaining phobic reactions describes an early attentional bias towards a feared
      stimulus followed by attentional avoidance of this stimulus. Such a pattern of
      attentional shifts might also be found when processing of pain-related stimuli is
      required. The purpose of the present study was to test the VAH for pain
      associated stimuli, i.e., faces displaying pain, using the method of eye-tracking
      in a pain-free sample. METHODS: Forty-eight healthy participants observed
      pictures of faces displaying pain and other emotions (anger, joy), presented
      concurrently with neutral faces, while their gaze behaviours were recorded
      continuously. RESULTS: Analysis of the time course of fixation durations revealed
      a distinct pattern for pain faces. Participants gazed at pain faces longer than
      at neutral faces at the beginning (up to 1000 ms) but reduced preference for pain
      faces increasingly thereafter (up to 2000 ms); this decline in vigilance did not
      occur for anger and joy faces. Strong fear of pain (Fear of Pain Questionnaire)
      tended to increase attentional preference for negative faces (pain, anger), a
      finding, which however did not reach significance. CONCLUSIONS: We assume that
      initial vigilance for pain-associated stimuli might reflect an adaptive reaction
      to detect a potentially harmful stimulus. Subsequently, the pain-associated
      stimulus might be less attended for the purpose of mood regulation when all clear
      is given in this situation.

PMID- 25370748
TI  - Spinal cord damage in Machado-Joseph disease.
AB  - Machado-Joseph disease (SCA3) is the most frequent spinocerebellar ataxia
      worldwide and characterized by remarkable phenotypic heterogeneity. MRI-based
      studies in SCA3 focused in the cerebellum and connections, but little is known
      about cord damage in the disease and its clinical relevance. To evaluate the
      spinal cord damage in SCA3 through quantitative analysis of MRI scans. A group of
      48 patients with SCA3 and 48 age and gender-matched healthy controls underwent
      MRI on a 3T scanner. We used T1-weighted 3D images to estimate the cervical
      spinal cord area (CA) and eccentricity (CE) at three C2/C3 levels based on a semi
      automatic image segmentation protocol. The scale for assessment and rating of
      ataxia (SARA) was employed to quantify disease severity. The two groups-SCA3 and
      controls-were significantly different regarding CA (49.5 +/- 7.3 vs 67.2 +/- 6.3
      mm(2), p < 0.001) and CE values (0.79 +/- 0.06 vs 0.75 +/- 0.05, p = 0.005). In
      addition, CA presented a significant correlation with SARA scores in the patient
      group (p = 0.010). CE was not associated with SARA scores (p = 0.857). In the
      multiple variable regression, we found that disease duration was the only
      variable associated with CA (coefficient = -0.629, p = 0.025). SCA3 is
      characterized by cervical cord atrophy and antero-posterior flattening. In
      addition, the spinal cord areas did correlate with disease severity. This
      suggests that quantitative analyses of the spinal cord MRI might be a useful
      biomarker in SCA3. 

PMID- 25370747
TI  - Gene flow in environmental Legionella pneumophila leads to genetic and pathogenic
      heterogeneity within a Legionnaires' disease outbreak.
AB  - BACKGROUND: Legionnaires' disease is a severe form of pneumonia caused by the
      environmental bacterium Legionella pneumophila. Outbreaks commonly affect people
      with known risk factors, but the genetic and pathogenic complexity of L.
      pneumophila within an outbreak is not well understood. Here, we investigate the
      etiology of the major Legionnaires' disease outbreak that occurred in Edinburgh,
      UK, in 2012, by examining the evolutionary history, genome content, and virulence
      of L. pneumophila clinical isolates. RESULTS: Our high resolution genomic
      approach reveals that the outbreak was caused by multiple genetic subtypes of L.
      pneumophila, the majority of which had diversified from a single progenitor
      through mutation, recombination, and horizontal gene transfer within an
      environmental reservoir prior to release. In addition, we discover that some
      patients were infected with multiple L. pneumophila subtypes, a finding which can
      affect the certainty of source attribution. Importantly, variation in the
      complement of type IV secretion systems encoded by different genetic subtypes
      correlates with virulence in a Galleria mellonella model of infection, revealing
      variation in pathogenic potential among the outbreak source population of L.
      pneumophila. CONCLUSIONS: Taken together, our study indicates previously cryptic
      levels of pathogen heterogeneity within a Legionnaires' disease outbreak, a
      discovery that impacts on source attribution for future outbreak investigations.
      Furthermore, our data suggest that in addition to host immune status, pathogen
      diversity may be an important influence on the clinical outcome of individual
      outbreak infections.

PMID- 25370749
TI  - Streptozotocin-induced type-1-diabetes disease onset in Sprague-Dawley rats is
      associated with an altered intestinal microbiota composition and decreased
      diversity.
AB  - There is a growing appreciation that microbiota composition can significantly
      affect host health and play a role in disease onset and progression. This study
      assessed the impact of streptozotocin (STZ)-induced type-1-diabetes (T1D) on
      intestinal microbiota composition and diversity in Sprague-Dawley rats, compared
      with healthy controls over time. T1D was induced by injection of a single dose
      (60 mg STZ kg(-1)) of STZ, administered via the intraperitoneal cavity. Total DNA
      was isolated from faecal pellets at weeks 0 (pre-STZ injection), 1, 2 and 4 and
      from caecal content at week 5 from both healthy and T1D groups. High-throughput
      16S rRNA sequencing was employed to investigate intestinal microbiota
      composition. The data revealed that although intestinal microbiota composition
      between the groups was similar at week 0, a dramatic impact of T1D development on
      the microbiota was apparent post-STZ injection and for up to 5 weeks. Most
      notably, T1D onset was associated with a shift in the Bacteroidetes : Firmicutes
      ratio (P<0.05), while at the genus level, increased proportions of lactic acid
      producing bacteria such as Lactobacillus and Bifidobacterium were associated with
      the later stages of T1D progression (P<0.05). Coincidently, T1D increased caecal
      lactate levels (P<0.05). Microbial diversity was also reduced following T1D
      (P<0.05). Principle co-ordinate analyses demonstrated temporal clustering in T1D
      and control groups with distinct separation between groups. The results provide a
      comprehensive account of how T1D is associated with an altered intestinal
      microbiota composition and reduced microbial diversity over time. 

PMID- 25370751
TI  - A previously uncharacterized tetratricopeptide-repeat-containing protein is
      involved in cell envelope function in Rhizobium leguminosarum.
AB  - Rhizobium leguminosarum is a soil bacterium that is an intracellular symbiont of
      leguminous plants through the formation of nitrogen-fixing root nodules. Due to
      the changing environments that rhizobia encounter, the cell is often faced with a
      variety of cell altering stressors that can compromise the cell envelope
      integrity. A previously uncharacterized operon (RL3499-RL3502) has been linked to
      proper cell envelope function, and mutants display pleiotropic phenotypes
      including an inability to grow on peptide-rich media. In order to identify
      functional partners to the operon, suppressor mutants capable of growth on
      complex, peptide-rich media were isolated. A suppressor mutant of a non-polar
      mutation to RL3500 was chosen for further characterization. Transposon
      mutagenesis, screening for loss of the suppressor phenotype, led to the
      identification of a Tn5 insertion in an uncharacterized tetratricopeptide-repeat
      containing protein RL0936. Furthermore, RL0936 had a 3.5-fold increase in gene
      expression in the suppressor strain when compared with the WT and a 1.5-fold
      increase in the original RL3500 mutant. Mutation of RL0936 decreased desiccation
      tolerance and lowered the ability to form biofilms when compared with the WT
      strain. This work has identified a potential interaction between RL0936 and the
      RL3499-RL3502 operon that is involved in cell envelope development in R.
      leguminosarum, and has described phenotypic activities to a previously
      uncharacterized conserved hypothetical gene. 

PMID- 25370752
TI  - Childhood trauma, parental death, and their co-occurrence in relation to current
      suicidality risk in adults: a nationwide community sample of Korea.
AB  - Although previous studies have suggested that childhood trauma and parental death
      are strongly associated with suicidality in adulthood, it is still unclear how
      these factors interact within the same population. A total of 1396 adults were
      recruited through nationwide multistage probability sampling in South Korea.
      Subjects were evaluated through face-to-face interviews using the Suicidality
      Module of the Mini-International Neuropsychiatric Interview and the Early Trauma
      Inventory Self Report-Short Form. Among the 1396 adults, the group that
      experienced both childhood trauma and parental death had the highest current
      suicidality risks (F = 12.16, p < 0.0001) and lifetime suicide attempt (chi2 =
      35.81, p < 0.0001) compared with the other groups, which were only childhood
      trauma, only parental death, and neither. Multivariate logistic regression
      analyses revealed that middle-to-high current suicidality risk and lifetime
      suicide attempt were significantly associated with concurrent childhood trauma
      and parental death (odds ratio, 3.64; 95% confidence interval, 1.99-6.65) as well
      as with only childhood trauma (odds ratio, 1.95; 95% confidence interval, 1.33
      2.87), after adjusting for age, sex, education, marital status, household monthly
      income, and living area. Emotional abuse was the only type of childhood trauma
      significantly associated with higher current suicidality scores in those who
      experienced childhood parental death than in those who did not (F = 3.26, p =
      0.041). Current suicidality risk and lifetime suicide attempt are associated with
      experiencing both parental death and trauma, especially emotional abuse, in
      childhood, whereas experiencing only childhood parental death is associated with
      neither.

PMID- 25370750
TI  - A quinol oxidase, encoded by cyoABCD, is utilized to adapt to lower O2
      concentrations in Rhizobium etli CFN42.
AB  - Bacteria have branched aerobic respiratory chains that terminate at different
      terminal oxidases. These terminal oxidases have varying properties such as their
      affinity for oxygen, transcriptional regulation and proton pumping ability. The
      focus of this study was a quinol oxidase encoded by cyoABCD. Although this
      oxidase (Cyo) is widespread among bacteria, not much is known about its role in
      the cell, particularly in bacteria that contain both cytochrome c oxidases and
      quinol oxidases. Using Rhizobium etli CFN42 as a model organism, a cyo mutant was
      analysed for its ability to grow in batch cultures at high (21 % O2) and low (1
      and 0.1 % O2) ambient oxygen concentrations. In comparison with other oxidase
      mutants, the cyo mutant had a significantly longer lag phase under low-oxygen
      conditions. Using a cyo :: lacZ transcriptional fusion, it was shown that cyo
      expression in the wild type peaks between 1 and 2.5 % O2. In addition, it was
      shown with quantitative reverse transcriptase PCR that cyoB is upregulated
      approximately fivefold in 1 % O2 compared with fully aerobic (21 % O2)
      conditions. Analysis of the cyo mutant during symbiosis with Phaseolous vulgaris
      indicated that Cyo is utilized during early development of the symbiosis.
      Although it is commonly thought that Cyo is utilized only at higher oxygen
      concentrations, the results from this study indicate that Cyo is important for
      adaptation to and sustained growth under low oxygen. 

PMID- 25370753
TI  - [Complications and prophylaxis strategies of posterior hemivertebra resection for
      congenital scoliosis].
AB  - OBJECTIVE: To evaluate the surgical outcomes and related complications of
      posterior hemivertebra resection with transpedicular instrumentation in the
      treatment of congenital scoliosis caused by fully-segmented non-incarcerated
      hemivertebra. METHODS: From January 2003 to January 2012, one hundred and forty
      consecutive cases of congenital scoliosis treated by posterior hemivertebra
      resection with transpedicular instrumentation were investigated retrospectively.
      Radiographs were reviewed to determine the type and location of the hemivertebra,
      the coronal curve magnitude, sagittal alignment, compensatory cranial curve and
      compensatory caudal curve preoperatively, postoperatively and at the latest
      follow-up. Operative reports and patient charts were reviewed to record operation
      time, fusion level and complications. RESULTS: One hundred and fifty-one
      posterior hemivertebra resections in 140 patients aged 2 to 45 years (average
      10.8 years) with non-incarcerated hemivertebra were evaluated. All the patients
      were followed up from 3 to 119 months (average 25 months). The average fusion
      level was 5.0 segments (2-11 segments). There was a mean improvement of 71.3% in
      the segmental scoliosis from 42.5 degrees  before surgery to 10.6 degrees  at the
      time of the latest follow-up, and a mean improvement of 66.8% in segmental
      kyphosis from 29.5 degrees  to 7.2 degrees  at the same periods. There were 14
      complications (13 patients), 3 pedicle fractures, 2 rod breakages, 2 pedicle
      elongation, 2 removed implants for prominent implants, 2 delayed wound healing, 2
      additional surgeries for curve progression, 1 prolonged respiratory support.
      There was no neurological complication. CONCLUSIONS: Posterior hemivertebra
      resection with transpedicular instrumentation is a safe and effective procedure
      for congenital scoliosis patients.Neurological complication is rare, but implant
      related complication still remains a challenge.

PMID- 25370754
TI  - [Imaging study of paravertebral muscle degeneration in degenerative lumbar
      instability].
AB  - OBJECTIVES: To compare the paravertebral muscle (such as multifidus, erector
      spinae, psoas muscle) changes between the patients with degenerative lumbar
      instability and normal person by MRI and to observe the degeneration of
      paravertebral muscles. To analyze the relationship between paravertebral muscle
      degeneration and lumbar curvature of degenerative lumbar instability. METHODS:
      Sixty patients with degenerative lumbar instability were retrospectively enrolled
      from December 2011 to July 2013 as degeneration group, meanwhile 60 health
      persons with no degenerative lumbar instability were selected as control group.
      No significant differences were found in the gender, age and body mass index
      between the two groups. The cross-sectional area(CSA) and percentage of fat
      infiltration area (FIA) of the paravertebral muscles at the L4-S1 levels were
      measured using T2-weighted axial MRI and Image J soft ware. And the lumbar
      curvature(expressed as lumbar lordosis angle) of all the patients in lumbar X-ray
      were measured in the two groups. The measured data were analyzed with independent
      samples t-test. RESULTS: The difference of multifidus cross-sectional area and
      the percentage of fat infiltration in the patients of degenerative lumbar
      instability at the L4-L5, L5-S1 level, compared with the control group, was
      statistically significant (t = 2.768, t = 6.216, P < 0.05). Between the two
      groups, the percentage of fatty infiltration in erector spinae showed significant
      differences (t = 5.862, P < 0.05). The cross-sectional area of erector spinae and
      the degeneration of the psoas muscle between the two groups was not statistically
      significant. The lumbar lordsis angle in the patients with degenerative lumbar
      instability was (43.9 +/- 15.6) degrees , which was higher than the (39.3 +/-
      14.2) degrees  in control group (t = 2.915, P < 0.05). CONCLUSIONS: Compared with
      the control group, patients with degenerative lumbar instability exists erector
      spinae and multifidus muscle degeneration, and erector spinae is more obvious.
      The degeneration among psoas muscle, erector spinae and multifidus muscle are
      inconsistent, which may be related to the increasing of the lumbar lordosis angle
      in the patients with degenerative lumbar instability.

PMID- 25370755
TI  - [Individualized surgical treatment of complex middle cerebral artery aneurysms].
AB  - OBJECTIVE: To summarize individualized surgical treatment strategies for complex
      middle cerebral artery (MCA) aneurysms. METHODS: Twenty patients with complex MCA
      aneurysms treated by microsurgery in Chinese People's Liberation Army General
      Hospital between December 2009 and November 2012 were retrospectively analyzed.
      There were 12 male and 8 female patients, with a mean age of 43 years (range: 14
      58 years). Giant aneurysms (size > 2.5 cm) were found in 6 cases, wide-neck
      aneurysms in 7 cases and serpentine ones in 3 patients. Important perforators
      were involved in aneurysm neck in 2 cases. Important branches originated from
      aneurysms in 6 patients. Two patients harbored recurrent aneurysms after coiling.
      Individualized surgical strategies were planned according to preoperative
      imaging. A frontotemporal approach was routinely used. Intraoperative
      somatosensory evoked potential monitoring, indocyanine green videoangiography and
      microvascular Doppler ultrasonography were regularly used. A postoperative
      digital subtraction angiography (DSA) or computed tomography angiography (CTA)
      was performed to verify the efficacy of treatment and patency of bypass vessels.
      RESULTS: Of the 20 cases, 7 aneurysms were clipped with clipping and
      reconstruction of parent artery with multiple clips, 3 M1 segment aneurysms were
      proximally occluded with extra-intracranial high-flow revascularization, 2
      aneurysms were treated with aneurysmectomy with superficial temporal artery to
      middle cerebral artery low-flow revascularization, 1 aneurysm was treated with
      aneurysmectomy with superficial temporal artery to middle cerebral artery low
      flow revascularization and branch side-to-side anastomosis, 2 aneurysms were
      treated with aneurysmectomy and re-anastomosis of parent artery, 1 aneurysm was
      treated with aneurysmectomy and re-anastomosis of parent artery and
      reinplantation of lenticulostriate artery, 3 bilateral MCA aneurysms were clipped
      by unilateral approach, and 1 was trapped. Nineteen patients were favorable with
      Glasgow Outcome Scale score 4-5 at discharge, and 1 patient died of cardiac
      infarction one week after surgery. The mean clinical follow-up was 20 months
      (range: 6-39 months). During follow-up, no bleeding occurred. DSA or CTA
      confirmed absence of aneurysm in 14 cases and residual neck in 2 patients. The
      other 3 patients were lost to follow-up. CONCLUSIONS: Individualized, multi
      modality surgical treatment strategies are effective and safe solution for
      treatment of complex MCA aneurysms. Revascularization remains imperative surgical
      technique.

PMID- 25370756
TI  - [Transperitoneal and retroperitoneal laparoscopic ureteroureterostomy for
      retrocaval ureter].
AB  - OBJECTIVE: To analyze the results of transperitoneal and retroperitoneal
      laparoscopic ureteroureterostomy procedure in the treatment of patients with
      retrocaval ureter. METHODS: From May 2004 to December 2012, 18 patients including
      12 male and 6 female patients were operated for retrocaval ureter, the average
      age was (37 +/- 10) years (range 17-55 years). Eight patients underwent
      transperitoneal laparoscopic ureteroureterostomy (transperitoneal laparoscopic
      group), and the other 10 patients' laparoscopic procedure were performed via
      retroperitoneal approach(retroperitoneal laparoscopic group). These patients'
      records were retrospectively analyzed for perioperative characteristics,
      complications and follow-up results. A two-tailed Student's t-test was used to
      compare perioperative data between the two groups. RESULTS: Technical success was
      acquired in all 18 laparoscopic procedures. Mean operative time of
      transperitoneal and retroperitoneal laparoscopic group was (85 +/- 20) minutes
      (60-130 minutes) and (98 +/- 30) minutes (70-180 minutes) , respectively. There
      was no difference in operation time between the two groups (t = 1.03, P > 0.05).
      The blood loss was less than 50 ml in all the patients. Comparison of anal
      exhaust time between the two groups showed no statistic difference (t = 0.16, P >
      0.05). No perioperative complication was observed. Intravenous pyelography or CT
      urography 3 months after the operation revealed a widely patent anastomosis with
      considerable improvement in hydronephrosis in all patients. There was no
      recurrence at a mean follow up of (40 +/- 24) months (range 12-115 months).
      CONCLUSION: Both transperitoneal and retroperitoneal laparoscopic
      ureteroureterostomy are effective and minimally invasive surgical alternative for
      the management of retrocaval ureter.

PMID- 25370757
TI  - [Analysis of the surgical strategy for the treatment of pineal region tumors].
AB  - OBJECTIVE: To evaluate and explore the optimal surgical strategy for the
      normalized treatment of pineal region tumors. METHODS: From September 2007 to
      February 2012, 43 patients were treated in Chinese People's Liberation Army
      General Hospital, including 30 male and 14 female patients, with pineal region
      tumors and non-communicating hydrocephalus were enrolled, who were 1-52 years
      old, mean age was (27 +/- 4) years. The clinical records, treatment strategy, and
      prognosis were retrospectively analyzed. All the patients routinely underwent
      endoscopic third ventriculostomy (ETV) and tumor biopsy as the initial treatment.
      Twenty-seven cases (62.8%, pure endoscopic group) with histological diagnosis of
      germinoma (23 cases) or pineoblastoma (4 cases) were treated with chemotherapy
      with/without radiation therapy after ETV. The rest 16 cases (37.2%, craniotomy
      group) with histological diagnosis of non-germinoma and non-pineoblastoma (5
      astrocytomas, 4 pineocytomas, 4 teratomas, 2 ependymomas, and 1 pineopappiloma)
      had craniotomy and tumor resection after ETV. All the cases had routine follow-up
      at 1, 3, and 6 months after the final surgery. The clinical, imaging, and tumor
      markers analysis were routinely examined at follow-up. RESULTS: In the pure
      endoscopic group, 1 case had intra-ventricular hemorrhage after ETV, followed by
      external ventricular drainage and recovered after 1 week. Endoscopic procedure
      related short-term ( < 3 months) complication rate was 2.3% (1/43), while long
      term morbidity was 0. All cases in the pure endoscopic group had chemotherapy
      with/without radiation therapy. Long-term follow-up results showed that all cases
      were cured or had progression free survival (PFS). In the craniotomy group, 2
      cases (2/16) developed intra-cranial hemorrhage after surgery, and had to be
      operated again for hematoma evacuation. In the craniotomy group, the short-term (
      < 3 months) morbidity rate was 6/16. At 3 months follow-up, 1 case still had
      homonymous hemianopia, which made the long-term morbidity rate was 1/16.
      CONCLUSIONS: For pineal region tumors with non-communicating hydrocephalus,
      simultaneous ETV with tumor biopsy can be the most favorable initial diagnostic
      and therapeutic treatment. Second-stage treatment (chemotherapy, radiation
      therapy, or craniotomy with tumor resection) can be selected according to the
      histological diagnosis.

PMID- 25370759
TI  - [Preliminary clinical application of vascular interventional robot].
AB  - OBJECTIVE: To verify the feasibility and safety of the vascular interventional
      vascular interventional surgical robot system applied to vascular interventional
      operation. METHODS: From March to September 2013, 10 patients had undergone robot
      assisted cerebral angiography. There were 6 male and 4 female patients; aged from
      19 to 58 years, with an average age of 38.4 years. The operation were carried out
      by neurosurgeons and vascular interventional robot. After successfully implanted
      of femoral artery sheath by hand, the catheter was fixed on the robot, under the
      guidance of navigation image the surgeon manipulate the master part and control
      the slave part of robot by sending command through network transmission, finally
      finished the whole cerebral angiography. The operation time was recorded from
      placing the sheath into femoral artery to finishing cerebrovascular selective
      angiography, simultaneously the time of staff under exposure of X ray was
      recorded, and the position difference between the setted targets and the actual
      position(positioning accuracy). RESULTS: It took 25-41 minutes to finish the
      cerebral angiography, the average time was (31 +/- 5) minutes, and the robot
      assisted angiography went quickly and smoothly without surgical complications.
      The remote positioning accuracy was (1.03 +/- 0.23) mm. The time of staff under
      exposure of X ray was 0 minute, the entire experimental process was basically
      implemented mechanization and automation. CONCLUSION: This system basically
      achieves initial medical purposes, such as reducing the radiation, facilitating
      interventional procedures on the basis of enhancing the image navigation,
      shorting the operation time, and improve the quality of operation.

PMID- 25370758
TI  - [Clinical outcome of deep sternal wound infection after cardiac surgery].
AB  - OBJECTIVE: To retrospectively evaluate the results of deep sternal wound
      infection (DSWI) after cardiac surgery. METHODS: Between January 2010 and
      September 2013, 139 patients suffering from DSWI after median sternotomy. The
      incidence of DSWI was 0.47% (139/29 574). There were 111 (79.9%) male and 28
      (20.1%) female patients. The mean age was (61 +/- 11) years, the mean body weight
      was (74 +/- 14) kg. The incidence of postoperative DSWI was 0.88% (91/10 341)
      after isolated coronary artery bypass grafting (CABG), 0.70% (15/2 143) after
      valve surgery or other cardiac surgery plus CABG, 0.21% (24/11 429) after valve
      surgery, 0.15% (3/2 002) after thoracic aortic surgery, and 0.19% (6/3 158) after
      congenital heart disease. The sternotomy was re-opened and extensive debridement
      of the wound was performed in all patients. When the wound was clean and there
      was a bed of fresh granulation tissue, the sternum was rewired. The surgical
      procedure performed included debridement, drainage, sternal wire reclosure and
      pectoralis major muscular transpositions depended on the clinical condition of
      the patient. RESULTS: The in-hospital mortality was 9.3%. Failure of secondary
      sternal refixation appeared in 15 (10.8%) patients, the reoperation procedure of
      these 15 patients was pectoralis major muscular transpositions. Other
      complications included sepsis in 13 patients, perivalvular leakage in 3 patients,
      and cardiac rupture during the surgical procedure in 3 patients. The mean
      hospitalization was (39 +/- 30) days. CONCLUSION: Deep sternal wound infection is
      a life-threatening complication after cardiac surgery associated with high
      morbidity and mortality.

PMID- 25370760
TI  - [Endovascular exclusion of peripheral aneurysms with polytetrafluoroethene stent
      graft].
AB  - OBJECTIVE: To evaluate the value and clinical effect of peripheral aneurysms with
      polytetrafluoroethene (PTFE) stent graft after peripheral endovascular
      procedures. METHODS: From May 2012 to November 2013, 13 patients of peripheral
      aneurysms were treated with PTFE stent graft. There were 9 male and 4 female
      patients, aged from 24 to 74 years with a mean of 52 years. There were 7
      aneurysms and 6 pseudoaneurysms. This stent graft was a self-expanding nitinol
      stent, internally covered by an ultra-thin polytetrafluoroethene (PTFE) graft.
      All peripheral aneurysms were repaired with the PTFE stent graft, using an
      entirely percutaneous approach. All patients were given clopidogrel and (or)
      aspirin postoperatively. Complications and reintervention rates were also
      examined. RESULTS: PTFE stent graft placement was successfully performed in all
      the 13 cases, and the instant isolation effect was quite satisfactory. During the
      follow-up period of 3 to 18 months, no stent graft related complications occurred
      in all patients except one patient with iliac arterial pseudoaneurysm, who
      developed pseudoaneurysms presented as a complication at puncture site. There
      were no other symptomatic complications with graft patience. CONCLUSION:
      Endovascular repair can be considered as an effective treatment strategy for
      peripheral aneurysms by PTFE stent graft.

PMID- 25370761
TI  - [Effects of carotid endarterectomy on cognitive function in patients with carotid
      stenosis].
AB  - OBJECTIVE: To investigate the theraputic effects of carotid endarterectomy (CEA)
      on cognitive function in patients with carotid stenosis (CAS) and congnitive
      impairment. METHODS: CEA was performed on 38 patients with CAS from December 2011
      to July 2013. There were 26 male and 12 female patients, with an average age of
      (70 +/- 7) years. Patients was underwent neuropsychological examinations (NPEs)
      including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment
      (MoCA) at 1 week before and 6 weeks after treatment. Cerebral perfusion was
      assessed with MR perfusion-weighted imaging and diffusion-weighted inmaging at 1
      week before and 6 weeks after treatment. RESULTS: All of the 38 patients
      completed NPEs and MRI at baseline and 6 weeks after CEA. After therapy, the
      parameters and the extents of abnormal perfusion was improved, including the
      decrease of time to peak (29 +/- 9 vs. 23 +/- 4), relative mean transit time (22
      +/- 8 vs. 14 +/- 6), arrive time (21 +/- 8 vs. 15 +/- 4) and relative cerebral
      blood volume (11.6 +/- 3.5 vs. 7.5 +/- 3.2) (t = 1.31 to 5.24, all P < 0.05).
      Significant improvement in MoCA (20.4 +/- 1.5 vs. 22.0 +/- 1.6, t = -4.25, P =
      0.000) but MMSE (26.16 +/- 1.35 vs. 26.47 +/- 1.52, t = -0.96, P = 0.341) was
      observed. CEA significantly improved the assessment of visuospacial/constructive
      abilities (2.4 +/- 0.9 vs. 2.8 +/- 0.7), naming (2.0 +/- 0.7 vs. 2.3 +/- 0.6),
      abstraction (1.2 +/- 0.7 vs. 1.6 +/- 0.6) and attention (2.3 +/- 0.6 vs. 2.6 +/-
      0.5) (t = 0.015 to 0.029, P = 0.015). CONCLUSION: CEA can improve the cognitive
      function of patients with carotid stenosis as well as the cerebral perfusion of
      patients and has therapeutic effects on vascular mild cognitive impairment.

PMID- 25370762
TI  - [Clinical application of totally implantable central venous port].
AB  - OBJECTIVE: To summarize the disposal methods and the reasons of complications in
      operation of totally implantable central venous port (TICVP). METHODS: A total of
      2 007 patients were enrolled in this observational, single-center study between
      December 2008 and March 2013. TICVP implantation was performed with one small
      skin incision and subcutaneous puncture of subclavian or jugular vein. Patient's
      profiles, indications of port system, early and delayed complications, and
      disposal methods were evaluated. There were 38 male and 1 969 female patients,
      aged from 21 to 85 years, with a mean of 47.6 years. RESULTS: The mean duration
      of the TICVP system was (242 +/- 12) days, ranging from 9 to 1 243 days. The
      achievement rate of puncture in the right jugular vein (99.76%) was the highest.
      Sonographic approach using the internal jugular vein were better than the
      external landmark-guided technique (99.80% vs. 96.34%, chi2 = 29.905, P = 0.000).
      The rate of immediate complication was 0.80%, which included pneumothorax,
      hemothorax, lymphatic fistula and thrombosis. Early complications rate was 0.10%,
      which included pocket hematoma, catheter migration, venous thrombosis, port
      pocket infection, fibrin sheath formation. Late complications rate was 7.87%,
      which included catheter fracture, pinch-off syndrome, catheter-related
      bloodstream infection, fibrin sheath formation, catheter migration,
      extravasation, port inversion and port reveal. The rate of removal due to
      complications was 1.34% (27/2 007), and the early complication was higher (chi2 =
      8.053, P = 0.011). CONCLUSIONS: The low incidence of complications suggests that
      TICVP is safe and reliable for long term intermittent venous access. The results
      support the use of TICVP in the oncology patients and patients requiring long
      term intravenous therapy.

PMID- 25370763
TI  - [Global gene expression responses to Iodine-125 radiation in three human gastric
      cancer cell lines].
AB  - OBJECTIVE: To study genome-wide gene expression changes in gastric cancer cells
      after iodine-125 125(I) particle irradiation. METHODS: 125I particles were used
      to irradiate three gastric cancer cell lines of various differentiation
      levels:high (BGC-823) , medium (AGS) and low (NCI-N87) .Whole-genome gene
      expression was investigated with microarray. The gene expression in iodine-125
      irradiated and untreated cancer cells was compared, and the genes with transcript
      levels altered for at least 2 folds (P < 0.05) were selected. The change in gene
      expression levels was verified by using quantitative real-time (qRT) -PCR.
      RESULTS: The three gastric cancer cell lines received the same dose rate of 125I
      particle irradiation. Cluster analysis showed that the Gene Ontology (GO)
      categories did not change in the three cell lines, but changes in gene expression
      levels were evident for many genes. After 125I particle irradiate NCI-N87 cells,
      895 genes were up-regulated, 786 genes were down-regulated; AGS was irradiated by
      125I seed, there were 124 genes upregulated, 161 genes were down-regulated; BGC
      823 cells were treated by 125I seed irradiation, 2 412 genes upregulated, 3 243
      downregulated genes. After ionizing radiation can cause very complex
      transcriptional regulation changes, KEGG pathway analysis shows that these
      differentially expressed genes overlap in a particular cell pathway. Four genes,
      TRAF3IP2-AS1, SDC1, RABL2B and NOM, were found having at least 2-fold difference
      in expression (P < 0.05) , and the gene expression alteration was confirmed by
      qRT-PCR. CONCLUSIONS: 125I particle irradiation caused gene expression changes in
      gastric cancer cells. The expressions of TRAF3IP2-AS1, SDC1, RABL2B and NOM are
      altered significantly in all three cell lines studied, indicating that these
      genes may play an important role in the 125I seed treatment of gastric cancer.
      These genes could be potential targets for developing anti-cancer drugs in the
      future.

PMID- 25370764
TI  - [Expression and localization of the nuclear factor-kappaB classical signaling
      pathway in the radial artery of diabetic patients].
AB  - OBJECTIVE: To observe the expression and localization of the nuclear factor
      kappaB (NF-kappaB) classic signaling pathway in the radial artery of the coronary
      artery bypass grafting (CABG) patients with diabetes and non-diabetes. METHODS:
      Samples of radial artery from 36 cases of diabetic and non-diabetic patients were
      randomly collected from January 2012 to December 2012.In the diabetic group there
      were 13 male cases, 5 female cases, with an average age of (69 +/- 6) years.In
      non-diabetes group there were 13 male cases, 5 female cases, with an average age
      of (70 +/- 6) years.HE staining techniques was used to test the morphology of
      radial artery. Immunohistochemical techniques was then used to test the
      expression and localization of key factors (inhibitor of kappa B kinase beta
      (IKKbeta), P50, P65, tumor necrosis factor-alpha (TNF-alpha) and endothelial
      nitric oxide synthase (eNOS)) in the NF-kappaB classical signaling pathway in the
      two groups of patients. RESULTS: The radial artery intima was signifiantly
      thickened in the diabetic patients when compared with non-diabetic patients by HE
      staining. And there wss a lot of inflammation and foam cell infiltration in the
      radial artery intima of the diabetic patients. Using immunohistochemical
      techniques the expression of IKKbeta, P50, P65 in diabetic group were obviously
      higher than non-diabetic group (4.4 +/- 0.5 vs. 1.1 +/- 0.6, 4.8 +/- 0.7 vs. 1.2
      +/- 0.7, 4.2 +/- 0.4 vs. 1.6 +/- 0.7, t = 18.238, 15.052, 13.535, all P <
      0.01).In the aspect of inflammatory cytokines, the expression of TNF-alpha and
      eNOS factors in diabeics group were significantly higher than non-diabetic group
      (5.5 +/- 0.5 vs.1.4 +/- 0.7, 3.3 +/- 0.5 vs. 0.8 +/- 0.4, t = 20.118, 16.764, all
      P < 0.01) also. And the five kinds of protein were mainly located in radial
      artery intima layer cells in diabetic patients. CONCLUSIONS: Expression levels of
      5 key factors in NF-kappaB classic signaling pathway are significantly higher in
      radial artery intimal layer of diabetic patients than non-diabetic patient's. And
      Positive signals are more concentrated in the radial artery intima layer of
      cells.

PMID- 25370765
TI  - [Impact of AR-V7 expression on overall survival for patients with metastatic
      prostate cancer].
AB  - OBJECTIVE: To investigate the impact of androgen receptor splice variant 7 (AR
      V7) expression on overall survival for patients with metastatic prostate cancer.
      METHODS: The data of 113 diagnosed metastatic prostate cancer patients from
      January 2002 to June 2010 were collected retrospectively, including patient's age
      at diagnosis, prostate-specific antigen (PSA) level at diagnosis,Gleason score,
      clinical stage, PSA nadir during hormonal therapy, the time to PSA nadir, vital
      status, survival time and cause of death. The expression of AR-V7 in prostate
      cancer tissue was detected by using immunohistochemical staining. The correlation
      of AR-V7 expression and patient clinicopathological characteristics in all
      patients were analysed using Student t-test or Chi-square test. Cox proportional
      hazards regression models were used to evaluate the predictive role of AR-V7
      expression and patient characteristics for overall survival. RESULTS: The median
      PSA nadir was 0.7 ug/L (ranged from 0.0 to 143.0 ug/L). The median time to PSA
      nadir was 8.1 months (ranged from 0.9 to 71.0 months). The follow-up was
      performed until March 12, 2014. During the follow-up period, 67 of 113 metastatic
      prostate cancer patients (59.3%) died and the median overall survival was 96
      months (ranged from 5 to 135 months). The AR-V7 detection rate was 20.4%
      (23/113). The serum PSA level in patients with positively expression of AR-V7 was
      significantly higher than that without AR-V7 expression (t = 2.521, P = 0.013).
      Multivariate Cox regression analysis indicated that the expression of AR-V7 (HR =
      2.421, P = 0.002) and time to PSA nadir (HR = 1.019, P = 0.022) were independent
      prognostic factors of overall survival for metastatic prostate cancer patients.
      CONCLUSIONS: The expression of AR-V7 in prostate cancer tissues and time to PSA
      nadir during hormonal therapy are independent prognostic factors of overall
      survival for metastatic prostate cancer patients. Therapy targeting AR-V7 may
      improve prognosis of metastatic prostate cancer patients.

PMID- 25370766
TI  - Modern diagnostic approach to hereditary xanthinuria.
AB  - Hereditary xanthinuria (HX) is a rare inherited disorder caused by a deficiency
      of xanthine dehydrogenase/oxidase (XDH/XO). Missing XDH/XO activity leads to
      undetectable levels of uric acid excessively replaced by xanthine in serum/urine.
      The allopurinol loading test has been traditionally used to differentiate between
      HX types I and II. Final confirmation of HX has been based on the biopsy finding
      of the absent XDH/XO activity in the small intestine or liver. We present the
      clinical, biochemical, ultrasound and molecular genetics findings in three new
      patients with HX and suggest a simple three-step approach to be used for
      diagnosis, typing and confirmation of HX. In the first step, the diagnosis of HX
      is determined by extremely low serum/urinary uric acid excessively replaced by
      xanthine. Second, HX is typed using urinary metabolomics. Finally, the results
      are confirmed by molecular genetics. We advocate for this safe and non-invasive
      diagnostic algorithm instead of the traditional allopurinol loading test and
      intestinal or liver biopsy used in the past. 

PMID- 25370767
TI  - [Perioperative chemotherapy in gastric cancer treatment - the surgeons view].
AB  - Contemporary European gastric cancer treatment guidelines recommend a short
      course of perioperative chemotherapy. This is supported by several randomized
      studies in which patients with perioperative chemotherapy had longer overall
      survival and better results in other parameters too (progression free survival,
      time to progression). The analysis of surgical therapy is given in this article.
      According to published data, in some patients extend of the surgery did not
      fulfill the requirements of contemporary surgical standards of care.

PMID- 25370768
TI  - [Basic biological roles of galectins in tissue repair and tumor growth].
AB  - Galectins are representatives of endogenous lectins - molecules specifically
      recognizing distinct sugar motifs. They play an important role in the processes
      of cell proliferation, differentiation, migration and extracellular matrix
      formation. Furthermore, galectins are able to transfer cellular signals and to
      participate in intercellular interaction. It has been proven that galectins play
      an important role in the formation of tumor and/or wound healing
      microenvironment. This review contains an overview of experimental and clinical
      studies dealing with biological roles of galectins in tissue repair and in its
      parallel - the tumor growth.

PMID- 25370769
TI  - [Calcium, dairy products and weight reduction].
AB  - Considerable attention is focused on calcium and other components of milk in
      terms of nutritional factors in the context of overweight and obesity. Studies
      have shown that calcium, proteins, branched amino acids and bioactive whey
      peptides in particular may help to reduce weight and improve body composition
      during weight loss, especially in terms of fat free mass (FFM) loss prevention. A
      diet with a higher content of proteins and calcium is also relevant to the
      regulation of food intake and improves overall patient compliance with weight
      management.

PMID- 25370770
TI  - [Mutagenic effect of advanced paternal age in neurocardiofaciocutaneous
      syndrome].
AB  - BACKGROUND: Increased frequency of chromosomal aberration in children of mothers
      aged 35 years and older is very well known and since 1973 it is an indication to
      investigate the foetal karyotype in cells obtained by invasive method
      (amniocentesis), because the genetic risk of severe affection is higher than the
      risk of necessary invasive method. Mutagenic effect of advanced paternal age is
      known only among geneticists (1-4). The reason is not only low absolute risk of
      new mutation but particularly a high number of involved genes and last not least
      the limited spectrum of autosomal dominant disorders without abiotrofic
      character. Therefore the preventive methods for elimination of this risk are very
      limited. Only a few of them could be recognized prenatally by noninvasive methods
      of prenatal diagnostics. METHODS: Genealogical, anamnestic and clinical data of
      83 patients were studied with clinical suspection on neurocardiofaciocutaneous
      syndrome (NCFCs) (5-7). The diagnosis has not been confirmed in 29 patients, no
      mutation was detected in 8 investigated genes (PTPN11, SOS1, HRAS, BRAF, RAF1,
      MEK1, KRAS, NRAS). In 54 patients with autosomal dominant inherited Noonan
      syndrome, Costello syndrome and cardiofaciocutaneous syndrome the diagnosis was
      confirmed on DNA level and the biological fitness was estimated for each
      disorder. Paternal age at conception was compared in the group of patients with
      familial and sporadic occurrence of Noonan and NCFC syndromes. The clinical
      prognosis of this disorder is represented by biological fitness of patients.
      Coefficient of selection is 0,6 in Noonan and LEOPARD syndromes (29 from 48). All
      6 patients with Costello and cardiofaciocutaneous syndromes developed due to a
      new mutation. CONCLUSION: Paternal age at birth was studied in 83 children
      patients with autosomal dominant Neurocardiofaciocutaneous syndrome (Noonan,
      LEOPARD, Costello, CFC) with a high population incidence and decreased biological
      fitness. Due to severe congenital heart defects, failure to thrive in infancy,
      increased risk for malignancy and further health problems the clinical prognosis
      of patients in the past was not good. Therefore high mutation rate is expected
      until now. Identification of genes responsible for manifestation of this
      disorder, enables to confirm the diagnosis and to recognize inherited and de novo
      mutations. Genealogy and DNA analysis of PTPN11, SOS1, HRAS, BRAF, RAF1, MEK1,
      KRAS and NRAS were obtained in cohort of 54 patients with NCFC syndromes and
      their parents. There were 48 patients with Noonan and LEOPARD syndromes, in 29
      cases due to mutation de novo, 19 patients inherited the mutation from one of
      parents. All 6 patients with Costello syndrome and CFC syndrome were affected due
      to new mutation. DNA analysis revealed 32 mutations in PTPN11 gene, mutation in
      SOS1 gene was found in 10 patients, RAF1 mutation was present in 3 patients;
      mutation in MEK1, KRAS and NRAS genes was present in one patient each. In
      Costello syndrome and CFC syndrome mutations in HRAS (4 patients) and BRAF (2
      patients) genes were detected. Genealogic data allow analysing parental age in
      the group of patients with new mutation and inherited mutation. Paternal age at
      conception of patients with Noonan syndrome due to new mutation was significantly
      increased in comparison to the group of fathers of Noonan patients with inherited
      mutation - 38,4 years and 29,6 years, resp., range 28 to 55 years and 25 to 35
      years, resp. Maternal age was slightly increased too, -30,9 and 27,7, resp. and
      range 24 to 42 years and 21 to 36 years, resp. but not significantly. The results
      support the mutagenic effect of paternal age, espec. autosomal dominant
      mutations.

PMID- 25370771
TI  - [Centres for Tobacco-Dependent in the Czech Republic in 2012: overview and
      economy].
AB  - BACKGROUND: Since 2005, in the Czech Republic the Centres for Tobacco-Dependent
      are being established at hospitals. METHODS: Evaluation of the activity of these
      37 centres in 2012, economic analysis of treatment costs and assessment of the
      cost of life year gained (LYG). RESULTS: Most of the centres (26 of 37) are based
      at pulmonary clinics with opening hours for smokers: on average 7 hours/week.
      Treatment codes 25501 and 25503 are used at 28 centres. Entry visit usually takes
      on average 61 minutes, follow-up visits 22 minutes. Nicotine replacement therapy
      and varenicline are indicated in all centres, but only 14 centres use bupropion.
      Virtually all centres use links to other clinical disciplines, about 10.5 % of
      patients are sent to other departments. The most common barriers for wider
      activity are insufficient salaries and staffing. In 2012, the Centre for Tobacco
      Dependent at the 3rd Medical Department, 1st Faculty of Medicine, Charles
      University in Prague and the General University Hospital treated 430 patients for
      the price of 3792 CZK per treated patient ( 150 Euro), respectively, with 38 %
      success rate for the price of 10,003 CZK per abstinent patient ( 400 Euro), or
      for 1,334 CZK per LYG ( 50 Euro/LYG). CONCLUSION: In the future it would be good
      to improve working conditions in centres and to take advantage of their potential
      for the indispensable, effective and highly cost-effective treatment.

PMID- 25370772
TI  - [Which ethics for medical ethics? Homage to Hans Jonas, 1903-1993].
AB  - Hans Jonas, one of the greatest philosophers of the 20th century, devoted several
      studies to the ethics in context with medicine and/or to the new biomedical
      research. His main thoughts in this field are presented (death and dying,
      mortality, reflections on experimenting with human subjects - nontherapeutic
      research, cloning, chimaeras). He was a man of wisdom and his humanity and moral
      sensibility are a matter of admiration. His ethics is in full consent with ethics
      and the dignity of medical profession. His ideas are compared (and contrasted)
      with those of the new bio"ethics".

PMID- 25370773
TI  - [Horizon 2020, new EU Framework programme for research and innovation, 2014
      2020].
AB  - Horizon 2020 is a financial instrument implementing the Innovation Union, a
      Europe 2020 flagship initiative aimed at securing Europes global competitiveness.
      Running from 2014 to 2020 with a budget of just over ? 80 billion, the EUs new
      programme for research and innovation is part of the drive to create new growth
      and jobs in Europe. Societal challenge Health, demographic change and wellbeing
      is an important part of Horizon 2020.

PMID- 25370775
TI  - Research in prehospital emergency medicine: comparison by geographic origin of
      publications.

PMID- 25370776
TI  - Differential expression of circulating miRNAs in maternal plasma in pregnancies
      with fetal macrosomia.
AB  - Macrosomia is associated with problems at birth and has life-long health
      implications for the infant. The aim of this study was to profile the plasma
      microRNAs (miRNAs or miRs) and evaluate the potential of circulating miRNAs to
      predict fetal macrosomia. The expression levels of miRNAs in plasma samples
      obtained from pregnant women with fetal macrosomia and from women with normal
      pregnancies (controls) were analyzed using TaqMan Low-Density Arrays (TLDAs)
      followed by quantitative reverse transcription polymerase chain reaction (RT
      qPCR) validation and analysis. The TLDA data revealed that 143 miRNAs were
      differentially expressed in the plasma samples from pregnant women with fetal
      macrosomia compared with the controls (43 upregulated and 100 downregulated
      miRNAs). Twelve of these miRNAs were selected for RT-qPCR analysis. Receiver
      operational characteristic (ROC) curve analysis indicated that several miRNAs
      (e.g., miR-141-3p and miR-200c-3p) were clearly distinguished between pregnancies
      with fetal macrosomia and other types of abnormal pregnancy and healthy
      pregnancies with high sensitivity and specificity (AUC >0.9). The expression of
      miRNA clusters also showed a similar trend in pregnancies with fetal macrosomia.
      This study provides a platform for profiling circulating miRNAs in maternal
      plasma. Our data also suggest that altered levels of maternal plasma miRNAs have
      great potential to serve as non-invasive biomarkers and as a mechanistic
      indicator of abnormal pregnancies.

PMID- 25370777
TI  - Sonocrystallization yields monoclinic paracetamol with significantly improved
      compaction behavior.
AB  - Ultrasound-assisted crystallization (sonocrystallization) was used to prepare a
      mixture of nano- and micrometer-sized crystals of the monoclinic form of
      paracetamol-a widely used analgesic known for its particularly problematic
      mechanical behavior under compression (i.e. poor tabletability). The nano- and
      micrometer-sized crystals yielded a powder which exhibits elastic moduli and bulk
      cohesions that are significantly higher than those observed in samples consisting
      of macrometer-sized crystals, thus leading to enhanced tabletability without the
      use of excipients, particle coating, salt, or cocrystal formation. Experimental
      compaction and finite element analysis were utilized to rationalize the
      significantly improved compaction behavior of the monoclinic form of paracetamol.

PMID- 25370779
TI  - Defining new surrogate markers for CKD progression.
AB  - At a recent meeting of international experts on clinical aspects of progressive
      chronic kidney disease (CKD), an extensive analysis of extant clinical trials was
      used to develop more effective and economical surrogate markers for CKD outcomes
      in adults. This article describes the reasons for this undertaking, the methods
      and conclusions of the meeting, and the relevance of these findings to pediatric
      nephrology. 

PMID- 25370780
TI  - A quantitative microfluidic angiogenesis screen for studying anti-angiogenic
      therapeutic drugs.
AB  - Anti-angiogenic therapy, which suppresses tumor growth by disrupting oxygen and
      nutrient supply from blood to the tumor, is now widely accepted as a treatment
      for cancer. To investigate the mechanisms of action of these anti-angiogenesis
      drugs, new three dimensional (3D) cell culture-based drug screening models are
      increasingly employed. However, there is no in vitro high-throughput screening
      (HTS) angiogenesis assay that can provide uniform culture conditions for the
      quantitative assessment of physiological responses to chemoattractant reagents
      under various concentrations of anti-angiogenesis drugs. Here we describe a
      method for screening and quantifying the vascular endothelial growth factor
      (VEGF)-induced chemotactic response on human umbilical vein endothelial cells
      (HUVECs) cultured with different concentrations of bortezomib, a selective 26S
      proteasome inhibitor. With this quantitative microfluidic angiogenesis screen
      (QMAS), we demonstrate that bortezomib-induced endothelial cell death is preceded
      by a series of morphological changes that develop over several days. We also
      explore the mechanisms by which bortezomib can inhibit angiogenesis. 

PMID- 25370781
TI  - mReg2 inhibits nuclear entry of apoptosis-inducing factor in mouse insulinoma
      cells.
AB  - We have reported earlier that murine-regenerating gene mReg2 protects MIN6 mouse
      insulinoma cells from ER stress and caspase-mediated apoptosis. In apoptotic
      cells, DNA damage is induced by the nuclear translocation of mitochondrial
      apoptosis-inducing factor (AIF). Here we tested the hypothesis that mReg2 may
      regulate Scythe and/or hsp70 which influence the nuclear import of AIF. Treatment
      with thapsigargin (Tg) or doxorubicin induced an increase in nuclear AIF in MIN6
      cells carrying the empty transfection vector (MIN6-VC) but not in cells
      overexpressing mReg2 (MIN6-mReg2). On one hand, nuclear Scythe was higher in the
      nucleus of MIN6-mReg2 compared with that in MIN6-VC cells. mReg2 did not alter
      the expression of AIF or Scythe. On the other hand, mReg2 induced the expression
      of hsp70 which is known to promote cytosolic retention of AIF. We conclude that
      mReg2 inhibits AIF-mediated apoptosis by promoting the nuclear presence of Scythe
      and inducing hsp70.

PMID- 25370782
TI  - Hydrophilic polymer microemboli in a patient with a chronic cutaneous ulcer: a
      case report.
AB  - Hydrophilic polymer coatings were designed to reduce friction between the
      catheter and vessel wall and facilitate intravascular manipulations during
      catheterization and placement of drug-eluting stents. One newly reported
      complication of such hydrophilic coatings is the fragmentation and embolization
      of the polymer, which can lead to ischemia and infarct by blocking the small
      vasculature. In this report, we present a patient with a non-healing ulcer on the
      leg. Biopsy from the ulcer revealed the presence of hydrophilic polymer emboli
      within the dermal vessels. This is one of the few reports of such a complication
      involving the skin. Our objective is to emphasize the histopathologic features of
      this uncommon iatrogenic phenomenon. 

PMID- 25370778
TI  - Drug-induced acid-base disorders.
AB  - The incidence of acid-base disorders (ABDs) is high, especially in hospitalized
      patients. ABDs are often indicators for severe systemic disorders. In everyday
      clinical practice, analysis of ABDs must be performed in a standardized manner.
      Highly sensitive diagnostic tools to distinguish the various ABDs include the
      anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into
      five different categories in terms of their pathophysiology: (1) metabolic
      acidosis caused by acid overload, which may occur through accumulation of acids
      by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or
      exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates)
      mechanisms or by decreased renal acid excretion (e.g., distal renal tubular
      acidosis by amphotericin B, nonsteroidal anti-inflammatory drugs, vitamin D); (2)
      base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide,
      aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or
      cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid
      and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or
      extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads:
      milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate
      administration; and (5) respiratory acidosis or alkalosis resulting from drug
      induced depression of the respiratory center or neuromuscular impairment (e.g.,
      anesthetics, sedatives) or hyperventilation (e.g., salicylates, epinephrine,
      nicotine). 

PMID- 25370783
TI  - The 'Can't intubate can't oxygenate' scenario in pediatric anesthesia: a
      comparison of the Melker cricothyroidotomy kit with a scalpel bougie technique.
AB  - BACKGROUND: While the majority of pediatric intubations are uncomplicated, the
      'Can't intubate, Can't Oxygenate' scenario (CICO) does occur. With limited
      management guidelines available, CICO is still a challenge even to experienced
      pediatric anesthetists. OBJECTIVES: To compare the COOK Melker cricothyroidotomy
      kit (CM) with a scalpel bougie (SB) technique for success rate and complication
      rate in a tracheotomy on a cadaveric 'infant airway' animal model. METHODS: Two
      experienced proceduralists repeatedly attempted tracheotomy in eight rabbits,
      alternately using CM and SB (4 fr) technique. The first attempt was performed at
      the level of the first tracheal cartilage with subsequent experimental trials of
      insertion progressively more caudad. Success was defined as intratracheal
      placement of cannula as seen on bronchoscope. Complications were assessed both by
      bronchoscopic and macropathological appearance. RESULTS: 32 attempts were made at
      tracheotomy. CM had an overall success rate of 100% compared to a 75% success
      rate for SB. Success rate for the first attempt was dependent on the level of the
      tracheotomy (Level 1 100%, level 2 62.5% and level 3 & 4 25%). While CM was
      associated with lateral and/or posterior wall damage on
      bronchoscopy/macropathology in 6% of 19% and 25% of 50% respectively, the damage
      observed was greater and more frequent with SB (19%/44% and 31%/50%,
      respectively). CONCLUSIONS: At level 1, the first attempt success rate was 100%
      for both devices. Overall CM showed a better success rate than SB; however, both
      techniques were associated with significant complication rates, which were more
      pronounced following the scalpel bougie technique.

PMID- 25370784
TI  - Stakeholders' perceptions of transferability criteria for health promotion
      interventions: a case study.
AB  - BACKGROUND: The effects of health promotion interventions are the result not only
      of the interventions themselves, but also of the contexts in which they unfold.
      The objective of this study was to analyze, through stakeholders' discourse, the
      characteristics of an intervention that can influence its outcomes. METHODS: This
      case study was based on semi-structured interviews with health promotion
      stakeholders involved in a regional program (PRALIMAP). General hypotheses on
      transferability and on how the intervention is presumed to produce its effects
      were used to construct an interview guide. Interviews were analyzed using
      thematic coding. RESULTS: Twenty-three stakeholders were interviewed. Results
      showed stakeholders made few references to population and environment
      characteristics. Three themes emerged as significant for the stakeholders:
      implementation modalities and methodology, modalities used to mobilize actors;
      and transferability-promoting factors and barriers. CONCLUSION: Our work
      contributes to a better understanding not only of transferability factors, but
      also of stakeholders' perceptions of them, which are just as important, because
      those perceptions themselves are a factor in mobilization of actors,
      implementation, and transferability.

PMID- 25370785
TI  - Intravenous Administration of Apomorphine Does NOT Induce Long QT Syndrome:
      Experimental Evidence from In Vivo Canine Models.
AB  - Apomorphine is a non-selective dopamine D1/D2 receptor agonist, which has been
      used for patients with Parkinson's disease and reported to induce QT interval
      prolongation and cardiac arrest. To clarify their causal link, we assessed the
      cardiovascular and pharmacokinetic profile of apomorphine with the halothane
      anaesthetized canine model (n = 4), whereas pro-arrhythmic potential of
      apomorphine was analysed with the chronic atrioventricular block canine model (n
      = 4). In the halothane-anaesthetized model, 0.01 mg/kg, i.v. of apomorphine
      hydrochloride over 10 min., providing about 10 times of its therapeutic
      concentration, increased the heart rate and ventricular contraction; 0.1 mg/kg
      over 10 min., providing about 100 times of the therapeutic, prolonged the
      ventricular effective refractory period; and 1 mg/kg over 10 min., providing
      about 1000 times of the therapeutic, decreased the ventricular contraction, mean
      blood pressure and cardiac output together with the intraventricular conduction
      delay and prolongation of the effective refractory period, whereas the left
      ventricular end-diastolic pressure, atrioventricular nodal conduction or
      ventricular repolarization were hardly affected. Meanwhile, in the
      atrioventricular block model, 1 mg/kg, i.v. of apomorphine hydrochloride over 10
      min. neither prolonged the QT interval nor induced torsade de pointes. These
      results suggest that apomorphine may possess a wide margin of cardiovascular
      safety contrary to our expectations.

PMID- 25370786
TI  - Sensory theories of developmental dyslexia: three challenges for research.
AB  - Recent years have seen the publication of a range of new theories suggesting that
      the basis of dyslexia might be sensory dysfunction. In this Opinion article, the
      evidence for and against several prominent sensory theories of dyslexia is
      closely scrutinized. Contrary to the causal claims being made, my analysis
      suggests that many proposed sensory deficits might result from the effects of
      reduced reading experience on the dyslexic brain. I therefore suggest that
      longitudinal studies of sensory processing, beginning in infancy, are required to
      successfully identify the neural basis of developmental dyslexia. Such studies
      could have a powerful impact on remediation.

PMID- 25370787
TI  - GLIA: oligodendrocytes rev up motor learning.

PMID- 25370788
TI  - Enhancement of ovarian cancer chemotherapy by delivery of multidrug-resistance
      gene small interfering RNA using tumor targeting Salmonella.
AB  - AIM: The aim of this study was to observe the effect of attenuated Salmonella
      typhi as a tumor-targeting delivery vector for multidrug-resistance gene (MDR1)
      small interfering RNA (siRNA). MATERIAL AND METHODS: The cisplatin (DDP)
      resistant ovarian cancer cell line SKOV-3/DDP was established by treatment with
      gradually increasing concentrations of cisplatin. MDR1 siRNA expression plasmid
      containing short hairpin RNA (shRNA) of MDR1 gene was constructed and transformed
      into attenuated Salmonella typhi strain  SL7207. SKOV-3/DDP cells were incubated
      with recombinant Salmonella and then subjected to analysis of MDR1 expression by
      real-time polymerase chain reaction and Western blot. SKOV-3/DDP tumor-bearing
      mice were established by subcutaneously injecting BALB/c nude mice with SKOV
      3/DDP cells, and were orally inoculated with Salmonella carrying MDR1 siRNA
      plasmid and simultaneously injected intraperitoneally with cisplatin. Tumor
      growth and mouse survival were observed. RESULTS: Compared with parental cell
      line, the DDP-resistant SKOV-3/DDP cells expressed a much higher level of MDR1.
      The expression of MDR1 in SKOV-3/DDP cells infected with the Salmonella strain
      bearing MDR1 siRNA plasmid in vitro was detected to be downregulated and DDP
      tolerance of these cells was reversed. Tumor-bearing nude mice that were orally
      receiving recombinant Salmonella experienced a slow tumor growth and became more
      sensitive to DDP. CONCLUSION: Attenuated Salmonella typhi may represent a
      promising vector for in vivo administration of RNA interference therapy against
      malignant tumors.

PMID- 25370789
TI  - Exercise pre-conditioning alleviates brain damage via excitatory amino acid
      transporter 2 and extracellular signal-regulated kinase 1/2 following ischemic
      stroke in rats.
AB  - Previous studies have reported that physical exercise may exert a neuroprotective
      effect in humans as well as animals. However, the detailed mechanisms underlying
      the neuroprotective effect of exercise has remained to be elucidated. The aim of
      the present study was to explore the possible signaling pathways involved in the
      protective effect of pre-ischemic treadmill training for ischemic stroke in rats.
      A total of 36 male Sprague-Dawley rats were divided at random into three groups
      as follows (n=12 for each): Sham surgery group; middle cerebral artery occlusion
      (MCAO) group; and exercise with MCAO group. Following treadmill training for
      three weeks, the middle cerebral artery was occluded for 90 min in order to
      induce ischemic stroke, followed by reperfusion. Following 24 h post-reperfusion,
      six rats from each group were assessed for neurological deficits and then
      sacrificed to calculate the infarct volume. The remaining rats (n=6 for each
      group) were sacrificed and the expression levels of excitatory amino acid
      transporter 2 (EAAT-2) and extracellular signal-regulated kinase 1/2 (ERK1/2)
      were detected using western blot analysis. The results of the present study
      demonstrated that rats that underwent pre-ischemic exercise intervention had a
      significantly decreased brain infarct volume and neurological deficits; in
      addition, the pre-ischemic exercise group showed decreased overexpression of
      phosphorylated ERK1/2 and increased expression of EAAT-2 following ischemic
      stroke. In conclusion, treadmill training exercise prior to ischemic stroke
      alleviated brain damage in rats via regulation of EAAT-2 and ERK1/2.

PMID- 25370790
TI  - Novel naphthoquinone derivatives and evaluation of their trypanocidal and
      leishmanicidal activities.
AB  - Herein, we report the synthesis of 12 new naphthoquinone derivatives, 6
      substituted 1,4-naphthoquinones and 6 heterocycle-fused naphthoquinones, as well
      as evaluation of their trypanocidal and leishmanicidal activities. Compounds 11a
      and 13a were active against the amastigote stage of T. cruzi and showed low
      cytotoxic effects. With respect to leishmanicidal assays, all compounds were
      inactive against the promastigote stages of L. chagasi and L. braziliensis. 

PMID- 25370791
TI  - Hiwi downregulation, mediated by shRNA, reduces the proliferation and migration
      of human hepatocellular carcinoma cells.
AB  - The Piwi subfamily is one of two Argonaute family proteins, which are
      characterized by the presence of Piwi and Piwi-Argonaute-Zwille domains, and are
      well known for their role in RNA silencing. Hiwi, a human member of the Piwi
      subfamily, is restricted to the germ line, where it binds Piwi-interacting RNAs
      and functions in stem cell self-renewal and gametogenesis. Previous reports have
      indicated that abnormal Hiwi expression may be associated with a poor prognosis
      of numerous types of human cancer, including hepatocellular carcinoma (HCC).
      However, little is currently known about the oncogenic role of Hiwi in HCC. In
      the present study, it was confirmed that Hiwi is overexpressed at both the mRNA
      and protein level, in HCC specimens, as well as in MHCC97L and MHCC97H HCC cell
      lines. A lentivirus-mediated small hairpin rna (shRNA) targeting Hiwi was
      constructed and used to infect MHCC97L and MHCC97H cells. Relative Hiwi mRNA and
      protein expression levels were determined by quantitative polymerase chain
      reaction and western blot analysis, respectively. Cell proliferation, migration
      and invasion were determined using cell count, scratch and Transwell assays,
      respectively. Hiwi mRNA and protein expression was significantly downregulated in
      HCC cells in response to transduction with the lentivirus-mediated shRNA.
      Furthermore, the proliferative, migrative and invasive properties of the shRNA
      transduced cells were significantly decreased. Therefore, Hiwi downregulation
      mediated by shRNA, may reduce the proliferation and migration of HCC cells. These
      results indicate that Hiwi may have an important role in the progression of HCC
      and may be a target for anticancer therapy. 

PMID- 25370792
TI  - Non-competitive Inhibition of Nicotinic Acetylcholine Receptors by Ladybird
      Beetle Alkaloids.
AB  - Ladybird beetles (Family Coccinellidae) secrete an alkaloid rich venom from their
      leg joints that protects them from predators. Coccinellines, the major venom
      constituents, are alkaloids composed of three fused piperidine rings that share a
      common nitrogen atom. Although many coccinellines have been isolated and
      chemically characterized, their pharmacological properties are essentially
      unknown. Using radioligand binding and functional assays we investigated the
      actions of several coccinellines on skeletal muscle and alpha7 nicotinic
      acetylcholine receptors (nAChRs). The alkaloids were shown to displace the
      specific binding of tritiated piperidyl-N-(1-(2-thienyl)cyclohexyl)-3,4
      piperidine ([(3)H]-TCP), which has been shown to bind deep within the ion channel
      of the electric fish (Torpedo) muscle nAChR. The stereoisomers precoccinelline
      and hippodamine (whose nitrogens are predicted to be ionized at physiological pH)
      and their respective analogs N-methyl-precoccinelline and N-methyl-hippodamine
      (whose quaternary nitrogens are permanently charged) displayed similar IC50s for
      inhibition of [(3)H]-TCP binding. However, the corresponding precoccinelline and
      hippodamine N-oxides, coccinelline and convergine (which have an electronegative
      oxygen bonded to an electropositive nitrogen) displayed significantly higher
      binding IC50s. Finally, exochomine, a dimeric coccinelline containing the
      hippodamine structure, displayed the highest IC50 (lowest affinity) for
      displacing specific [(3)H]-TCP binding. The presence of a desensitizing
      concentration (10(-3) M) of carbachol (CCh) had little or no effect on the
      affinity of the Torpedo nAChR for the three coccinellines tested. High
      concentrations of the coccinellid alkaloids did not affect binding of [(3)H]
      cytisine to Torpedo receptor ACh binding sites. Inhibition of the alpha7 nAChR
      with pre-equilibrated precoccinelline was insurmountable with respect to ACh
      concentration. We conclude that the coccinellines bind to one or more allosteric
      sites rather than to the ACh binding sites, and inhibit nAChR responses to ACh
      through a non-competitive mechanism. Future chemical and pharmacological
      investigations of other ladybird beetle alkaloids are likely to reveal other
      interesting alkaloids affecting ligand-gated receptors.

PMID- 25370793
TI  - Transplantation of olfactory ensheathing cells attenuates acute carbon monoxide
      poisoning-induced brain damages in rats.
AB  - In this study, the therapeutic effect of olfactory ensheathing cells (OEC)
      transplantation on brain damage was evaluated on acute carbon monoxide (CO)
      poisoning rat model. Two weeks after primary culture, OECs were microinjected
      into hippocampus of CO poisoning rats. Survival of OECs in the host was observed
      and quantified. OECs survived at 2 weeks, but surviving cell number was found
      sharply decreased at 6 weeks and reduced to less than 10(3) at 8 weeks after
      transplantation. At 2 weeks after transplantation, motor function test and
      cerebral edema assay were performed and followed by pathological examination
      including hematoxylin and eosin and immunohistochemistry staining to observe the
      neuron injury and synapsin I and growth associated protein-43 (GAP-43)
      expression. Furthermore, biomarkers of oxidative stress and apoptosis related
      proteins in the hippocampus were detected. The results showed that CO exposure
      led to neurological dysfunction and cerebral edema in rats. After OEC
      transplantation, neurological function was significantly improved and the
      cerebral edema was alleviated. In addition, the numbers of neurons and Nissl
      bodies were increased and synapsin I and GAP-43 protein expressions were
      upregulated in the hippocampus. Compared with CO poisoned rats, superoxide
      dismutase activity and glutathione content were both increased and methane
      dicarboxylic aldehyde level was decreased in the hippocampus of OEC transplanted
      rats. Moreover, OEC transplantation reduced apoptosis induced by CO exposure. The
      Bcl-2 expression was significantly upregulated and Bax expression was
      significantly downregulated. The activity of caspase-3 and the cleaved-poly ADP
      ribose polymerase expression were decreased. Taken together, our data suggest
      that OEC attenuates brain damages induced by acute CO poisoning within 2 weeks
      after transplantation.

PMID- 25370794
TI  - Prolyl carboxypeptidase activity decline correlates with severity and short-term
      outcome in acute ischemic stroke.
AB  - Prolyl carboxypeptidase (PRCP) is an enzyme associated with cerebrovascular risk
      factors such as hypertension, diabetes mellitus, obesity and hyperlipidemia. We
      aim to evaluate the relation between serum PRCP activity and severity, evolution
      and outcome of acute ischemic stroke. We used a specific RP-HPLC activity assay
      to measure PRCP activity in serum of 50 stroke patients at admission, and at 24
      h, 72 h and 7 days after stroke onset to assess correlations with stroke severity
      based on the National Institutes of Health Stroke scale score (NIHSS), infarct
      volume on brain MRI scan, stroke outcome based on the modified Rankin scale (mRS)
      and mortality at 3 months after stroke. The average PRCP activity in serum
      decreased significantly the first 24 h after stroke onset and returned to
      baseline values at day 7. High NIHSS scores and infarct volumes at admission were
      related with a more pronounced decrease of PRCP in the first 24 h after stroke
      (DeltaPRCP24, r = 0.31, P < 0.05; r = 0.30, P < 0.05). In addition, patients who
      displayed a more pronounced decrease in PRCP levels during the first 24 h after
      stroke were more likely to be institutionalized upon discharge (n = 21)
      (DeltaPRCP24 +/- SD, 0.05 +/- 0.10 U/L vs. 0.17 +/- 0.14 U/L, P = 0.001). The
      decrease in PRCP levels in the first 24 h after stroke onset is associated with
      stroke severity and an unfavourable short-term stroke outcome.

PMID- 25370795
TI  - Laparoscopic liver mobilization: tricks of the trade to avoid complications.
AB  - Laparoscopic liver resection is gaining popularity because of the availability of
      new laparoscopic instruments and advanced techniques. Laparoscopic liver
      mobilization is not only necessary for pure laparoscopic liver resection but also
      for laparoscopy-assisted hepatectomy. Laparoscopy-assisted hepatectomy
      significantly reduces the length of the laparotomy incision, and it is a good
      educational transition to the more advanced laparoscopic liver resection.
      Laparoscopic liver mobilization is a simple and easy procedure if surgeons know
      what challenges to expect. Here, the technique of liver mobilization is
      summarized, along with those challenges. 

PMID- 25370796
TI  - Key factors in achieving successful endoscopic dissection of rectal tumors: early
      results of 33 consecutive rectal endoscopic submucosal dissections in Polish
      academic center.
AB  - INTRODUCTION: The aim of the study was to investigate outcomes of rectal
      endoscopic dissection (ESDs) performed in a single academic institution in
      Poland. METHODS AND PATIENTS: Thirty-three consecutive cases of rectal ESDs were
      performed between June 2013 and April 2014. Effectiveness of dissection,
      complications, and the tumor recurrence after 3 months of treatment were than
      retrospectively investigated. RESULTS: The average size of the dissected tumor
      was 4.025 cm. Overall en-block resection rate was 70%. Follow-up examinations
      after 3 months so far were conducted in 15 patients. There was no local
      recurrence. In univariate analysis, the en-bloc resection rate was significantly
      higher in smaller lesions (P<0.001) and in patients undergone ESD in second half
      period of service duration. CONCLUSIONS: ESD of the rectal tumors is a valuable
      alternative treatment method for adenomas and T1 SM1 rectal cancers. The risk of
      serious complications and local recurrence is low.

PMID- 25370798
TI  - Clinical outcome of drug-eluting versus bare-metal stents in patients with
      calcified coronary lesions: a meta-analysis.
AB  - BACKGROUND: The relative safety and efficacy of drug-eluting stents (DES) versus
      bare-metal stents (BMS) in patients with calcified coronary lesions is still
      debated. AIMS: To evaluate clinical outcome of DES versus BMS in patients with
      calcified coronary lesions using a meta-analysis of the current literature.
      METHODS: We performed a systematic literature search using Medline, Embase,
      Cochrane and several other databases. Randomised controlled trials, prospective
      and retrospective cohort studies with a mean follow-up period >6 months were
      included. Primary efficacy was target lesions revascularisation (TLR) and primary
      end-point for safety was stent thrombosis. Secondary end-points were cardiac
      death and recurrent myocardial infarction (MI). RESULTS: Five trials were
      included in the meta-analysis, including 2440 patients (1230 in the DES group,
      1210 in the BMS group). TLR was significantly lower in patients treated with DES
      as compared with patients treated with BMS (8.5% vs 16.0%; odds ratio (OR) =
      0.50; 95% confidence interval (CI) 0.38-0.65; P < 0.00001). There were no
      significant differences in the incidence of stent thrombosis (0.9% vs 0.3%; OR =
      2.01; 95% CI 0.34-11.88; P = 0.44), cardiac death (3.3% vs 4.2%; OR = 0.81; 95%
      CI 0.50-1.30; P = 0.38) and recurrent MI (5.0% vs 5.2%; OR = 0.99; 95% CI, 0.66
      1.49; P = 0.97) between the two groups. Subgroup analysis by the sample size and
      follow-up duration showed that the associations were similar between DES versus
      BMS. CONCLUSIONS: DES significantly reduces TLR rates as compared with BMS in
      patients with calcified coronary lesions, with non-significant differences in
      terms of stent thrombosis, cardiac death and MI.

PMID- 25370797
TI  - A preclinical study on the efficacy and safety of a new vaccine against
      Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse
      models.
AB  - AIMS/HYPOTHESIS: Enterovirus infections have been implicated in the aetiology of
      autoimmune type 1 diabetes. A vaccine could be used to test the causal
      relationship between enterovirus infections and diabetes development. However,
      the development of a vaccine against a virus suspected to induce an autoimmune
      disease is challenging, since the vaccine itself might trigger autoimmunity.
      Another challenge is to select the enterovirus serotypes to target with a
      vaccine. Here we aimed to evaluate the function and autoimmune safety of a novel
      non-adjuvanted prototype vaccine to Coxsackievirus serotype B1 (CVB1), a member
      of the enterovirus genus. METHODS: A formalin-inactivated CVB1 vaccine was
      developed and tested for its immunogenicity and safety in BALB/c and NOD mice.
      Prediabetic NOD mice were vaccinated, infected with CVB1 or mock-treated to
      compare the effect on diabetes development. RESULTS: Vaccinated mice produced
      high titres of CVB1-neutralising antibodies without signs of vaccine-related side
      effects. Vaccinated mice challenged with CVB1 had significantly reduced levels of
      replicating virus in their blood and the pancreas. Prediabetic NOD mice
      demonstrated an accelerated onset of diabetes upon CVB1 infection whereas no
      accelerated disease manifestation or increased production of insulin
      autoantibodies was observed in vaccinated mice. CONCLUSIONS/INTERPRETATION: We
      conclude that the prototype vaccine is safe and confers protection from infection
      without accelerating diabetes development in mice. These results encourage the
      development of a multivalent enterovirus vaccine for human use, which could be
      used to determine whether enterovirus infections trigger beta cell autoimmunity
      and type 1 diabetes in humans.

PMID- 25370799
TI  - Frontline health workers as brokers: provider perceptions, experiences and
      mitigating strategies to improve access to essential medicines in South Africa.
AB  - BACKGROUND: Front-line health providers have a unique role as brokers (patient
      advocates) between the health system and patients in ensuring access to medicines
      (ATM). ATM is a fundamental component of health systems. This paper examines in a
      South African context supply- and demand- ATM barriers from the provider
      perspective using a five dimensional framework: availability (fit between
      existing resources and clients' needs); accessibility (fit between physical
      location of healthcare and location of clients); accommodation (fit between the
      organisation of services and clients' practical circumstances); acceptability
      (fit between clients' and providers' mutual expectations and appropriateness of
      care) and affordability (fit between cost of care and ability to pay). METHODS:
      This cross-sectional, qualitative study uses semi-structured interviews with
      nurses, pharmacy personnel and doctors. Thirty-six providers were purposively
      recruited from six public sector Community Health Centres in two districts in the
      Eastern Cape Province representing both rural and urban settings. Content
      analysis combined structured coding and grounded theory approaches. Finally, the
      five dimensional framework was applied to illustrate the interconnected facets of
      the issue. RESULTS: Factors perceived to affect ATM were identified. Availability
      of medicines was hampered by logistical bottlenecks in the medicines supply
      chain; poor public transport networks affected accessibility. Organization of
      disease programmes meshed poorly with the needs of patients with comorbidities
      and circular migrants who move between provinces searching for economic
      opportunities, proximity to services such as social grants and shopping centres
      influenced where patients obtain medicines. Acceptability was affected by, for
      example, HIV related stigma leading patients to seek distant services. Travel
      costs exacerbated by the interplay of several ATM barriers influenced
      affordability. Providers play a brokerage role by adopting flexible prescribing
      and dispensing for 'stable' patients and aligning clinic and social grant
      appointments to minimise clients' routine costs. Occasionally they reported
      assisting patients with transport money. CONCLUSION: All five ATM barriers are
      important and they interact in complex ways. Context-sensitive responses which
      minimise treatment interruption are needed. While broad-based changes
      encompassing all disease programmes to improve ATM are needed, a beginning could
      be to assess the appropriateness, feasibility and sustainability of existing
      brokerage mechanisms.

PMID- 25370800
TI  - Biological performance of cell-encapsulated methacrylated gellan gum-based
      hydrogels for nucleus pulposus regeneration.
AB  - Limitations of current treatments for intervertebral disc (IVD) degeneration have
      promoted interest in the development of tissue-engineering approaches. Injectable
      hydrogels loaded with cells can be used as a substitute material for the inner
      IVD part, the nucleus pulposus (NP), and provide an opportunity for minimally
      invasive treatment of IVD degeneration. The NP is populated by chondrocyte-like
      cells; therefore, chondrocytes and mesenchymal stem cells (MSCs), stimulated to
      differentiate along the chondrogenic lineage, could be used to promote NP
      regeneration. In this study, the in vitro and in vivo response of human bone
      marrow-derived MSCs and nasal chondrocytes (NCs) to modified gellan gum-based
      hydrogels was investigated. Both ionic- (iGG-MA) and photo-crosslinked (phGG-MA)
      methacrylated gellan gum hydrogels show no cytotoxicity in extraction assays with
      MSCs and NCs. Furthermore, the materials do not induce pro-inflammatory responses
      in endothelial cells. Moreover, MSCs and NCs can be encapsulated into the
      hydrogels and remain viable for at least 2 weeks, although apoptosis is observed
      in phGG-MA. Importantly, encapsulated MSCs and NCs show signs of in vivo
      chondrogenesis in a subcutaneous implantation of iGG-MA. Altogether, the data
      endorse the potential use of modified gellan gum-based hydrogel as a suitable
      material in NP tissue engineering. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25370801
TI  - Hemostatic status in liver transplantation: association between preoperative
      procoagulants/anticoagulants and postoperative hemorrhaging/thrombosis.
AB  - The delicate rebalanced hemostatic status of liver transplant recipients may lead
      to both hemorrhagic and thrombotic tendencies in this population. The aim of this
      study was to investigate the association between pretransplant
      procoagulants/anticoagulants and posttransplant bleeding and thrombosis among
      living donor liver transplant recipients. The study subjects were 403 consecutive
      recipients with chronic liver disease. Perioperative variables, including
      preoperative values for procoagulants and anticoagulants, were assessed to
      determine their association with posttransplant hemorrhaging and thrombosis.
      There were 35 hemorrhagic complications (9%) and 21 thrombotic complications
      (5%). In logistic regression analyses, a higher Model for End-Stage Liver Disease
      score (P = 0.01) and a lower fibrinogen value (P < 0.001) were independently
      associated with hemorrhaging, whereas only a lower protein C value (P < 0.001)
      was independently associated with thrombosis. In a receiver operating
      characteristic analysis, a low preoperative protein C value (with the most
      accurate cutoff value being 25%) was a reliable predictor of thrombotic
      complications after liver transplantation (area under the curve = 0.921, P <
      0.001, sensitivity = 0.9, specificity = 0.8). In conclusion, the decreases in
      both procoagulants and anticoagulants in liver transplant recipients may
      additively result in a delicate hemostatic balance and predispose patients to
      both hemorrhagic and thrombotic complications. A lower preoperative protein C
      value (<25%) was demonstrated to be a significant and reliable predictor of
      postoperative thrombotic complications in liver transplant recipients.

PMID- 25370803
TI  - Relationship between procalcitonin serum levels and functional outcome in stroke
      patients.
AB  - To determine whether serum procalcitonin (PCT) levels at admission were
      associated with short-term functional outcome after acute ischemic stroke (AIS)
      in a cohort Chinese sample. We prospectively studied 378 patients with AIS who
      were admitted within 24 h after the onset of symptoms. PCT and NIH stroke scale
      (NIHSS) were measured at the time of admission. Short-term functional outcome was
      measured by modified Rankin scale (mRS) 90 days after admission. The results
      indicated that the serum PCT levels were significantly higher in AIS patients as
      compared to normal controls (P < 0.0001). In the 114 patients with an unfavorable
      functional outcome, serum PCT levels were higher compared with those in patients
      with a favorable outcome (2.40 (IQR, 1.10-3.69) ng/mL and 0.42 (IQR, 0.10-1.05)
      ng/mL, respectively, P < 0.001). PCT was an independent prognostic marker of
      functional outcome [odds ratio (OR) 3.45 (2.29-4.77), adjusted for the NIHSS and
      other possible confounders] in patients with ischemic stroke, added significant
      additional predictive value to the clinical NIHSS score. In receiver operating
      characteristic curve analysis, the prognostic accuracy of PCT was higher compared
      to Hs-CRP and NIHSS score. PCT is an independent predictor of short-term
      functional outcome after ischemic stroke in Chinese sample even after correcting
      for possible confounding factors. 

PMID- 25370802
TI  - Up-regulation of Glis2 involves in neuronal apoptosis after intracerebral
      hemorrhage in adult rats.
AB  - The novel Kruppel-like zinc finger protein Gli-similar 2 (Glis2), one member of
      the transcription factors, is involved in controlling the flow of genetic
      information and the modulation of diverse cellular activities. Accumulating
      evidence has demonstrated its important roles in adult development and several
      diseases. However, information regarding the regulation and possible function of
      Glis2 in the central nervous system is still limited. In this study, we explored
      the roles of Glis2 during the pathophysiological process of intracerebral
      hemorrhage (ICH). An ICH rat model was established and assessed by behavioral
      tests. Expression of Glis2 was significantly up-regulated in brain areas
      surrounding the hematoma following ICH. Immunofluorescence showed that Glis2 was
      strikingly increased in neurons, but not astrocytes or microglia. Up-regulation
      of Glis2 was found to be accompanied by the increased expression of active
      caspase-3 and Bax and decreased expression of Bcl-2 in vivo and vitro studies.
      Moreover, knocking down Glis2 by RNA-interference in PC12 cells reduced active
      caspase-3 and Bax expression while increased Bcl-2. Collectively, we speculated
      that Glis2 might exert pro-apoptotic function in neurons following ICH. 

PMID- 25370804
TI  - Treatment adherence in patients with Alzheimer's disease referred to an Italian
      center for dementia.

PMID- 25370806
TI  - Measures of arthritis activity associated with patient-reported improvement in
      rheumatoid arthritis when assessed prospectively versus retrospectively.
AB  - OBJECTIVE: The patient global assessment (PGA) is intended to provide an
      integrated summary of all symptoms of arthritis, but it is not clear which
      disease features most impact patients' assessments of changes in their overall
      status. We investigated what aspects of rheumatoid arthritis (RA) activity
      correlated best with prospectively measured changes in the PGA and with patients'
      retrospective judgments of improvement. METHODS: We studied 250 patients with
      active RA in a prospective longitudinal study. Disease activity measures were
      collected before and after treatment escalation. Prospectively measured changes
      in PGA and patients' judgments of improvement or worsening at the followup visit
      were tested for correlations with changes in patient-reported measures of
      symptoms and functioning, joint counts, and laboratory tests. RESULTS: Patients
      improved during the study, with the mean +/- SD PGA decreasing from 55.6 +/- 25.2
      to 37.6 +/- 24.0. At the followup visit, 167 patients (66.8%) reported
      improvement in overall arthritis status. Changes in pain severity, stiffness
      severity, and fatigue were the only significant correlates of changes in PGA. In
      contrast, changes in the Health Assessment Questionnaire, tender joint count or
      Disease Activity Score in 28 joints (DAS28), and stiffness severity were
      associated with retrospective judgments of improvement. CONCLUSION: Prospectively
      measured changes in PGA in RA were related solely to other patient-reported
      measures, but patients' retrospective judgments of improvement were related to
      functional limitations, tender joint count, and DAS28. Patients' subjective
      judgments of improvement reflect aspects of RA different from the PGA and may be
      a simple complementary measure of treatment efficacy.

PMID- 25370805
TI  - Efficient bi-allelic gene knockout and site-specific knock-in mediated by TALENs
      in pigs.
AB  - Pigs are ideal organ donors for xenotransplantation and an excellent model for
      studying human diseases, such as neurodegenerative disease. Transcription
      activator-like effector nucleases (TALENs) are used widely for gene targeting in
      various model animals. Here, we developed a strategy using TALENs to target the
      GGTA1, Parkin and DJ-1 genes in the porcine genome using Large White porcine
      fibroblast cells without any foreign gene integration. In total, 5% (2/40), 2.5%
      (2/80), and 22% (11/50) of the obtained colonies of fibroblast cells were mutated
      for GGTA1, Parkin, and DJ-1, respectively. Among these mutant colonies, over 1/3
      were bi-allelic knockouts (KO), and no off-target cleavage was detected. We also
      successfully used single-strand oligodeoxynucleotides to introduce a short
      sequence into the DJ-1 locus. Mixed DJ-1 mutant colonies were used as donor cells
      for somatic cell nuclear transfer (SCNT), and three female piglets were obtained
      (two were bi-allelically mutated, and one was mono-allelically mutated). Western
      blot analysis showed that the expression of the DJ-1 protein was disrupted in KO
      piglets. These results imply that a combination of TALENs technology with SCNT
      can efficiently generate bi-allelic KO pigs without the integration of exogenous
      DNA. These DJ-1 KO pigs will provide valuable information for studying
      Parkinson's disease. 

PMID- 25370808
TI  - Sequential phase transformation of propeller-like C3-symmetric liquid crystals
      from a helical to ordered to disordered hexagonal columnar structure.
AB  - In this paper, we report thermally induced intercolumnar phase transitions of C3
      symmetric liquid crystals (LCs) bearing a triazole-based propeller-like aromatic
      mesogen. Since the constituting aromatic rings are conjugated through rotatable
      single bonds, the mesogenic shape is tuneable depending on the degree of
      conformational motion. Molecule 1 with ninefold octyl peripheries shows a
      hexagonal columnar liquid crystalline phase transition from ordered mesogenic
      stacking to disordered mesogenic stacking upon heating. On the other hand,
      molecule 2 with sixfold octyl peripheries displays a helical hexagonal columnar
      phase with the P6/mmm space group at ambient temperature as well as the ordered
      and disordered hexagonal columnar phases at higher temperatures. The
      intracolumnar helical order can be understood by an interdigitated stacking of
      the propeller-like mesogens along the columnar axis and the optimized space
      filling. Notably, all the intercolumnar phase transformations in this study are
      revealed as second-order transitions. The thermodynamic nature agrees well with
      the fact that the conformational motions of the C3-symmetric aromatic mesogen
      change abruptly with each columnar transition.

PMID- 25370807
TI  - First report of an exophilic Anopheles arabiensis population in Bissau City,
      Guinea-Bissau: recent introduction or sampling bias?
AB  - BACKGROUND: The malaria vector Anopheles arabiensis exhibits greater behavioural
      and ecological plasticity than the other major vectors of the Anopheles gambiae
      complex, which presents challenges for major control methods. This study reports
      for the first time the presence of An. arabiensis in Antula, a suburb of Bissau
      city, the capital of Guinea Bissau, where high levels of hybridization between
      Anopheles coluzzii and An. gambiae have been reported. Given that previous
      surveys in the area, based on indoor collections, did not sample An. arabiensis,
      the possibility of a recently introduced exophilic population was investigated.
      METHODS: Larval and adult mosquito collections were carried out in Antula at the
      end of the rainy season of 2010. Anopheles gambiae species composition,
      determined by rDNA-IGS and SINE200X6.1 markers, was compared with four previously
      collected samples dating back to 1993. Analysis of ten microsatellites was used
      to estimate levels of genetic diversity, relatedness and to investigate
      demographic stability. RESULTS: Anopheles arabiensis comprised 54.0% of larvae
      and 25.6% of adults collected in 2010, but was absent in all previous
      collections, a highly unlikely observation by chance if the population was
      stable. This species had the lowest levels of genetic diversity, highest
      relatedness and, along with An. gambiae, exhibited evidence of a recent
      population expansion. CONCLUSIONS: Results point to the presence of a previously
      undetected outdoor population of An. arabiensis in Antula, which appears to have
      expanded recently, highlighting the importance of complementing indoor-based
      mosquito collections with sampling methods targeting outdoor adults and immature
      stages for a more complete assessment of mosquito biodiversity. A change in
      temporal dynamics in the species complex composition was also detected. Coupled
      with previous evidence of asymmetric introgression from An. coluzzii to An.
      gambiae, this suggests that the study area may be subject to ecological changes
      with a potential impact on both the genetics of these species and on malaria
      transmission.

PMID- 25370809
TI  - Effect of microseparation on contact mechanics in metal-on-metal hip replacements
      A finite element analysis.
AB  - Some early failures of metal-on-metal (MoM) hip replacements associated with
      elevated wear have caused concerns for the use of this bearing combination.
      Simulator studies have shown that microseparation and its associated rim contact
      and edge loading may produce the most severe wear in MoM bearings. It is
      generally recognized that this high wear can be attributed to the high contact
      stress of the head on the rim of the cup. In this study, an improved finite
      element contact model that incorporates an elastic-perfectly plastic material
      property for cobalt-chrome alloy of the metal bearing was developed in an attempt
      to provide an accurate prediction of the stress and strain for the rim contact.
      The effects of the microseparation displacement (0.1-2 mm), cup inclination angle
      (25-65 degrees ) and cup rim radius (0.5-4 mm) on the contact stress/strain were
      investigated. The results show that a translational displacement >0.1 mm under a
      load >0.5 kN can produce a highly concentrated contact stress at the surface of
      the cup rim which can lead to plastic deformation. This study also suggests that
      the magnitude of translational displacement was the major factor that determined
      the severity of the contact conditions and level of stress and strain under
      microseparation conditions. Future studies will address the effect of surgical
      translational and rotational malposition and component design on the magnitude of
      microseparation, contact stress and strain and severity of wear.

PMID- 25370810
TI  - Transcriptome analysis of grey and white matter cortical tissue in multiple
      system atrophy.
AB  - Multiple system atrophy (MSA) is a distinct member of a group of
      neurodegenerative diseases known as alpha-synucleinopathies, which are
      characterized by the presence of aggregated alpha-synuclein in the brain. MSA is
      unique in that the principal site for alpha-synuclein deposition is in the
      oligodendrocytes rather than neurons. The cause of MSA is unknown, and the
      pathogenesis of MSA is still largely speculative. Brain transcriptome
      perturbations during the onset and progression of MSA are mostly unknown. Using
      RNA sequencing, we performed a comparative transcriptome profiling analysis of
      the grey matter (GM) and white matter (WM) of the frontal cortex of MSA and
      control brains. The transcriptome sequencing revealed increased expression of the
      alpha and beta haemoglobin genes in MSA WM, decreased expression of the
      transthyretin (TTR) gene in MSA GM and numerous region-specific long intervening
      non-coding RNAs (lincRNAs). In contrast, we observed only moderate changes in the
      expression patterns of the alpha-synuclein (SNCA) gene, which confirmed previous
      observations by other research groups. Our study suggests that at the
      transcriptional level, MSA pathology may be related to increased iron levels in
      WM and perturbations of the non-coding fraction of the transcriptome. 

PMID- 25370811
TI  - PASI90 response: the new standard in therapeutic efficacy for psoriasis.
AB  - In a non-life-threatening disease such as psoriasis, treatment goals should be
      referred to the improvement in severity and extent of the disease and their
      impact on patients' perceived health-related quality of life (HRQoL), usually
      measured by the Dermatology Life Quality Index (DLQI). The ultimate goal of
      therapy is blanching, and an improvement of 90% or better (PASI90 response) with
      respect to baseline Psoriasis Area and Severity Index (PASI) is considered as
      treatment success by the European Medicines Agency. PASI75 response has become
      accepted as a less stringent reasonable therapeutic goal, but absolute PASI
      values might provide a better benchmark, irrespective of baseline PASI. Anyway,
      objective measures of psoriasis involvement are clinically meaningful only if
      they correlate with significant improvements in DLQI, and especially with the
      achievement of a DLQI = 0-1 status, corresponding to lack of effect of the
      disease on patient's HRQoL. Even though PASI75 response meets therapeutic
      expectations in most patients, PASI90 response or better has a significantly
      higher impact on DLQI improvement and is associated with significantly higher
      DLQI = 0-1 response rates. The introduction of anti-IL17 drugs in clinical
      practice bears the promise of achieving PASI90 response or better in the majority
      of patients, and initial data suggest that the PASI90 benchmark provides better
      discriminatory value as regards achievement of DLQI = 0-1 response. Further
      research is required to confirm the value of absolute PASI cut-offs as a measure
      of therapeutic success independent of baseline and duration of treatment, and to
      develop newer, more practical and more accurate measures of psoriasis severity. 

PMID- 25370812
TI  - Primary and secondary endocrinopathies found in a patient with craniopharyngioma.

PMID- 25370813
TI  - Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3
      subunit D inhibits proliferation of HCT116 colon cancer cells.
AB  - Dysregulation of protein synthesis is emerging as a major contributory factor in
      cancer development. eIF3D (eukaryotic translation initiation factor 3 subunit D)
      is one member of the eIF3 (eukaryotic translation initiation factor 3) family,
      which is essential for initiation of protein synthesis in eukaryotic cells.
      Acquaintance with eIF3D is little since it has been identified as a dispensable
      subunit of eIF3 complex. Recently, eIF3D was found to embed somatic mutations in
      human colorectal cancers, indicating its importance for tumour progression. To
      further probe into its action in colon cancer, we utilized lentivirus-mediated
      RNA interference to knock down eIF3D expression in one colon cancer cell line
      HCT116. Knockdown of eIF3D in HCT116 cells significantly inhibited cell
      proliferation and colony formation in vitro. Flow cytometry analysis indicated
      that depletion of eIF3D led to cell-cycle arrest in the G2/M phase, and induced
      an excess accumulation of HCT116 cells in the sub-G1 phase representing apoptotic
      cells. Signalling pathways responsible for cell growth and apoptosis have also
      been found altered after eIF3D silencing, such as AMPKalpha (AMP-activated
      protein kinase alpha), Bad, PRAS40 [proline-rich Akt (PKB) substrate of 40 kDa],
      SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase), GSK3beta
      and PARP [poly(ADP-ribose) polymerase]. Taken together, these findings suggest
      that eIF3D might play an important role in colon cancer progression. 

PMID- 25370814
TI  - How I treat newly diagnosed chronic myeloid leukemia in 2015.
AB  - The initial treatment for chronic myeloid leukemia in chronic phase (CP-CML)
      represents a complex process, which includes a prompt and precise diagnosis, the
      choice among three available tyrosine kinase inhibitors (TKIs), and the initial
      management of care for these patients, which will protract over a very long
      period of time. This manuscript summarizes different data on activity, side
      effects, and supportive measures available for each TKI, the need for particular
      care in the logistical organization of CML management, the scenario which will be
      opened by the future availability of generic imatinib. The opinion of the authors
      is that imatinib remains the first-line treatment for CP-CML; this strategy,
      accompanied by intensive monitoring and possible dose modification/drug switch
      after the initial 3-12 months of treatment presently assures a normal life
      expectancy to the population of newly diagnosed patients with CP-CML.

PMID- 25370815
TI  - Tissue-factor-bearing microparticles (MPs-TF) in patients with acute ischaemic
      stroke: the influence of stroke treatment on MPs-TF generation.
AB  - BACKGROUND AND PURPOSE: Stroke is an important cause of death and disability
      throughout the world. Microparticles play a cardinal role in vascular hemostasis.
      The primary aim of this study was to evaluate the procoagulant activity of
      microparticles and levels of tissue-factor-bearing microparticles (MPs-TF),
      tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with
      acute ischaemic stroke. METHODS: Seventy-three patients with a diagnosis of acute
      ischaemic stroke were included. Venous blood samples were drawn on the first day
      and the seventh day after stroke onset. Plasma microparticles, MPs-TF, TF and
      TFPI were determined by enzyme-linked immunosorbent assay. Assessment variables
      were timing of blood collection, type of stroke treatment, presence or absence of
      diabetes mellitus and hypertension, and scores on the National Institutes of
      Health Stroke Scale together with scores on the modified Rankin Scale. RESULTS:
      Whilst MPs-TF and TFPI levels of stroke subjects were significantly higher
      (median, 1.63 vs. 0.73 pg/ml; median, 114.26 vs. 78.60 ng/ml, respectively), TF
      levels in the plasma of stroke patients were significantly lower (median, 82.27
      vs. 97.80 pg/ml) than those of healthy individuals. Lower levels of TF were
      detected in patients with severe stroke in comparison with patients with mild
      stroke. Moreover, the data also showed that in stroke patients not treated with
      alteplase the activity of microparticles was significantly higher 1 week after
      diagnosis in comparison with the activity at the time of diagnosis. CONCLUSION:
      Our findings suggest that patients with acute ischaemic stroke have increased
      generation of MPs-TF. Nevertheless, further studies are needed in order to
      confirm such inference.

PMID- 25370816
TI  - Simultaneous co-ingestion of prescription stimulants, alcohol and other drugs: a
      multi-cohort national study of US adolescents.
AB  - OBJECTIVE: To determine the past-year prevalence rates and correlates of
      simultaneous co-ingestion of prescription stimulants and other substances among
      US high school seniors. METHODS: Nationally representative probability samples of
      US high school seniors were surveyed as a part of the Monitoring the Future
      study. The sample consisted of five cohorts including a total of 12,431 high
      school seniors (modal age: 18 years) and represented a population that was 53%
      female. RESULTS: Among past-year nonmedical users of prescription stimulants (n =
      835), the estimated prevalence of any past-year simultaneous co-ingestion of
      prescription stimulants and other substances was 64.4%. The substances most
      commonly co-ingested with prescription stimulants included marijuana (51.1%) and
      alcohol (48.4%). Nonmedical users who co-ingested prescription stimulants with
      other substances were more likely to report non-oral routes of administration,
      recreational motives and greater subjective high when using prescription
      stimulants than nonmedical users who did not co-ingest prescription stimulants
      with other substances. CONCLUSIONS: The majority of past-year nonmedical users of
      prescription stimulants reported simultaneous co-ingestion of prescription
      stimulants and other substances. The findings indicate that co-ingestion of
      prescription stimulants and other substances is a pervasive behavior among US
      adolescents who engage in nonmedical use of prescription stimulants and should be
      carefully considered in future clinical practice and research.

PMID- 25370817
TI  - A combination of gene expression ranking and co-expression network analysis
      increases discovery rate in large-scale mutant screens for novel Arabidopsis
      thaliana abiotic stress genes.
AB  - As challenges to food security increase, the demand for lead genes for improving
      crop production is growing. However, genetic screens of plant mutants typically
      yield very low frequencies of desired phenotypes. Here, we present a powerful
      computational approach for selecting candidate genes for screening insertion
      mutants. We combined ranking of Arabidopsis thaliana regulatory genes according
      to their expression in response to multiple abiotic stresses (Multiple Stress
      [MST] score), with stress-responsive RNA co-expression network analysis to select
      candidate multiple stress regulatory (MSTR) genes. Screening of 62 T-DNA
      insertion mutants defective in candidate MSTR genes, for abiotic stress
      germination phenotypes yielded a remarkable hit rate of up to 62%; this gene
      discovery rate is 48-fold greater than that of other large-scale insertional
      mutant screens. Moreover, the MST score of these genes could be used to
      prioritize them for screening. To evaluate the contribution of the co-expression
      analysis, we screened 64 additional mutant lines of MST-scored genes that did not
      appear in the RNA co-expression network. The screening of these MST-scored genes
      yielded a gene discovery rate of 36%, which is much higher than that of classic
      mutant screens but not as high as when picking candidate genes from the co
      expression network. The MSTR co-expression network that we created,
      AraSTressRegNet is publicly available at http://netbio.bgu.ac.il/arnet. This
      systems biology-based screening approach combining gene ranking and network
      analysis could be generally applicable to enhancing identification of genes
      regulating additional processes in plants and other organisms provided that
      suitable transcriptome data are available. 

PMID- 25370818
TI  - Incorporation of a prolyl hydroxylase inhibitor into scaffolds: a strategy for
      stimulating vascularization.
AB  - Clinical applications of tissue engineering are constrained by the ability of the
      implanted construct to invoke vascularization in adequate extent and velocity. To
      overcome the current limitations presented by local delivery of single angiogenic
      factors, we explored the incorporation of prolyl hydroxylase inhibitors (PHIs)
      into scaffolds as an alternative vascularization strategy. PHIs are small
      molecule drugs that can stabilize the alpha subunit of hypoxia-inducible factor-1
      (HIF-1), a key transcription factor that regulates a variety of angiogenic
      mechanisms. In this study, we conjugated the PHI pyridine-2,4-dicarboxylic acid
      (PDCA) through amide bonds to a gelatin sponge (Gelfoam((r))). Fibroblasts
      cultured on PDCA-Gelfoam were able to infiltrate and proliferate in these
      scaffolds while secreting significantly more vascular endothelial growth factor
      than cells grown on Gelfoam without PDCA. Reporter cells expressing green
      fluorescent protein-tagged HIF-1alpha exhibited dose-dependent stabilization of
      this angiogenic transcription factor when growing within PDCA-Gelfoam constructs.
      Subsequently, we implanted PDCA-Gelfoam scaffolds into the perirenal fat tissue
      of Sprague Dawley rats for 8 days. Immunostaining of explants revealed that the
      PDCA-Gelfoam scaffolds were amply infiltrated by cells and promoted vascular
      ingrowth in a dose-dependent manner. Thus, the incorporation of PHIs into
      scaffolds appears to be a feasible strategy for improving vascularization in
      regenerative medicine applications. 

PMID- 25370819
TI  - The synergistic effect of SAHA and parthenolide in MDA-MB231 breast cancer cells.
AB  - The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA
      MB231 cells, a triple-negative breast cancer (TNBC) cell line, but its
      effectiveness was scarce when employed at low doses. This represents an obstacle
      for a therapeutic utilization of PN. In order to overcome this difficulty we
      associated to PN the suberoylanilide hydroxamic acid (SAHA), an histone
      deacetylase inhibitor. Our results show that SAHA synergistically sensitized MDA
      MB231 cells to the cytotoxic effect of PN. It is noteworthy that treatment with
      PN alone stimulated the survival pathway Akt/mTOR and the consequent nuclear
      translocation of Nrf2, while treatment with SAHA alone induced autophagic
      activity. However, when the cells were treated with SAHA/PN combination, SAHA
      suppressed PN effect on Akt/mTOR/Nrf2 pathway, while PN reduced the prosurvival
      autophagic activity of SAHA. In addition SAHA/PN combination induced GSH
      depletion, fall in Deltapsim, release of cytochrome c, activation of caspase 3
      and apoptosis. Finally we demonstrated that combined treatment maintained both
      hyperacetylation of histones H3 and H4 induced by SAHA and down-regulation of
      DNMT1 expression induced by PN. Inhibition of the DNA-binding activity of NF-kB,
      which is determined by PN, was also observed after combined treatment. In
      conclusion, combination of PN to SAHA inhibits the cytoprotective responses
      induced by the single compounds, but does not alter the mechanisms leading to the
      cytotoxic effects. Taken together our results suggest that this combination could
      be a candidate for TNBC therapy.

PMID- 25370820
TI  - Minimally invasive lumbar decompression for lumbar stenosis: review of clinical
      outcomes and cost effectiveness.
AB  - Lumbar stenosis patients typically present with neurogenic claudication or
      radiculopathy. Studies have shown the benefit of surgical management of lumbar
      stenosis for patients who fail medical management. Surgical management
      traditionally involved an open laminectomy and foramenotomies. The emergence of
      minimally invasive spinal surgery has allowed for comparable clinical outcomes to
      open laminectomies, with the potential additional benefits of decreased blood
      loss, shorter hospital stay, decreased postoperative narcotic requirement,
      decreased rate of infection, and the potential benefit of decreasing the risk of
      postoperative instability. A shorter length of stay and faster return to work
      after minimally invasive lumbar decompression may result in the minimally
      invasive approach being more cost effective than an open approach. A literature
      review was performed to evaluate the clinical outcomes and cost effectiveness
      associated with minimally invasive decompression of lumbar stenosis. 

PMID- 25370821
TI  - Photoassisted diversity-oriented synthesis: accessing 2,6-epoxyazocane
      (oxamorphan) cores.
AB  - The modular synthesis of photoprecursors and their photoinduced cyclization into
      substituted 1-benzazocanes of two distinct topologies is described. The key step
      producing an extended polyheterocyclic system involves the photogeneration of
      azaxylylenes and their subsequent intramolecular cycloaddition with furan
      containing pendants tethered either via the aniline nitrogen or through the
      carbonyl group containing arm. The primary photoproducts-secondary or tertiary
      anilines which are not acylated at the nitrogen atom-undergo facile acid
      catalyzed or spontaneous ring-opening-ring-closing rearrangement to yield fused
      polyheterocyclic structures possessing a 2,6-epoxyazocane (or oxamorphan) core. 

PMID- 25370822
TI  - The effect of riboflavin and ultraviolet light on the infectivity of arboviruses.
AB  - BACKGROUND: Arboviruses are an emerging threat to transfusion safety and rates of
      infection are likely to increase with the increased rainfall associated with
      climate change. Arboviral infections are common in Australia, where Ross River
      virus (RRV), Barmah Forest virus (BFV), and Murray Valley encephalitis virus
      (MVEV), among others, have the potential to cause disease in humans. The use of
      pathogen reduction technology (PRT) may be an alternative approach for blood
      services to manage the risk of arboviral transfusion transmission. In this study,
      the effectiveness of the Mirasol PRT (Terumo BCT) system at inactivating RRV,
      BFV, and MVEV in buffy coat (BC)-derived platelets (PLTs) was investigated. STUDY
      DESIGN AND METHODS: BC-derived PLT concentrates in additive solution (SSP+) were
      spiked with RRV, BFV, or MVEV and then treated with the Mirasol PRT system. The
      level of infectious virus was determined before and after treatment, and the
      reduction in viral infectivity was calculated. RESULTS: Treatment with PRT
      (Mirasol) reduced the amount of infectious virus of all three arboviruses. The
      greatest level of inactivation was observed for RRV (2.33 log; 99.25%), followed
      by BFV (1.97 log; 98.68%) and then MVEV (1.83 log; 98.42%). CONCLUSION: Our study
      demonstrates that treatment of PLT concentrates with PRT (Mirasol) reduces the
      infectious levels of RRV, BFV, and MVEV. The relevance of the level of reduction
      required to prevent disease transmission by transfusion has not been fully
      defined and requires further investigation. In the face of a changing climate,
      with its associated threat to blood safety, PRT represents a proactive approach
      for maintaining blood safety.

PMID- 25370823
TI  - Prokaryotic expression and purification of soluble goldfish Tgf2 transposase with
      transposition activity.
AB  - Goldfish Tgf2 transposon of Hobo/Activator/Tam3 (hAT) family can mediate gene
      insertion in a variety of aquacultural fish species by transposition; however,
      the protein structure of Tgf2 transposase (TPase) is still poorly understood. To
      express the goldfish Tgf2 TPase in Escherichia coli, the 2061-bp coding region
      was cloned into pET-28a(+) expression vector containing an N-terminal (His)6-tag.
      The pET-28a(+)-Tgf2 TPase expression cassette was transformed into Rosetta 1
      (DE3) E. coli lines. A high yield of soluble proteins with molecular weight of
      ~80 kDa was obtained by optimized cultures including low-temperature (22  degrees
      C) incubation and early log phase (OD600 = 0.3-0.4) induction. Mass spectrometry
      analysis following trypsin digestion of the recombinant proteins confirmed a Tgf2
      TPase component in the eluate of Ni(2+)-affinity chromatography. When co-injected
      into 1-2 cell embryos with a donor plasmid harboring a Tgf2 cis-element, the
      prokaryotic expressed Tgf2 TPase can mediate high rates (45 %) of transposition
      in blunt snout bream (Megalobrama amblycephala). Transposition was proved by the
      presence of 8-bp random direct repeats at the target sites, which is the
      signature of hAT family transposons. Production of the Tgf2 Tpase protein in a
      soluble and active form not only allows further investigation of its structure,
      but provides an alternative tool for fish transgenesis and insertional
      mutagenesis.

PMID- 25370824
TI  - New strategy for high-level expression and purification of biologically active
      monomeric TGF-beta1/C77S in Escherichia coli.
AB  - Mature transforming growth factor beta1 (TGF-beta1) is a homodimeric protein with
      a single disulfide bridge between Cys77 on the respective monomers. The synthetic
      DNA sequence encoding the mature human TGF-beta1/C77S (further termed TGF-beta1m)
      was cloned into plasmid pET-32a downstream to the gene of fusion partner
      thioredoxin (Trx) immediately after the DNA sequence encoding enteropeptidase
      recognition site. High-level expression (~1.5 g l(-1)) of Trx/TGF-beta1m fusion
      was achieved in Escherichia coli BL21(DE3) strain mainly in insoluble form. The
      fusion was solubilized and refolded in glutathione redox system in the presence
      of zwitterionic detergent CHAPS. After refolding, Trx/TGF-beta1m fusion was
      cleaved by enteropeptidase, and the carrier protein of TGF-beta1m was separated
      from thioredoxin on Ni-NTA agarose. Separation of monomeric molecules from the
      noncovalently bounded oligomers was done using cation-exchange chromatography.
      The structure of purified TGF-beta1m was confirmed by circular dichroism
      analysis. The developed technology allowed purifying biologically active tag-free
      monomeric TGF-beta1m from bacteria with a yield of about 2.8 mg from 100 ml cell
      culture. The low-cost and easy purification steps allow considering that our
      proposed preparation of recombinant monomeric TGF-beta1 could be employed for in
      vitro and in vivo experiments as well as for therapeutic intervention.

PMID- 25370825
TI  - Universal real-time PCR-based assay for lentiviral titration.
AB  - Lentiviral vectors are efficient vehicles for stable gene transfer in both
      dividing and non-dividing cells. This feature among others makes lentiviral
      vectors a powerful tool in molecular research. However, the use of lentiviruses
      in research studies and clinical trials requires a precise and validated
      titration method. In this study, we describe a qPCR-based approach for estimation
      of lentiviral vector titer (pLV-THM-GFP). The use of WPRE (Woodchuck Hepatitis
      Virus Posttranscriptional Regulatory Element) and albumin genes as templates for
      an SYBR green-based real-time qPCR method allows for a rapid, sensitive,
      reproducible, and accurate assessment of lentiviral copy number at an integrated
      lentiviral DNA level. Furthermore, this optimization enables measurement of
      lentiviral concentration even in very poor quality and small quantity material.
      Consequently, this approach provides researchers with a tool to perform low-cost
      assessment with highly repeatable results.

PMID- 25370826
TI  - Homologous recombinatorial cloning without the creation of single-stranded ends:
      exonuclease and ligation-independent cloning (ELIC).
AB  - We describe a new type of molecular cloning that complements the available
      strategies for homologous recombinatorial cloning. Purified, linear double
      stranded DNA molecules with homologous ends are simply mixed in water and they
      transform readily into E. coli. Insert and linear vector need as few as ten base
      pairs of homologous sequence at their ends and essentially no incubation or
      enzyme treatments are needed for creating recombinants from linear fragments. Our
      method outcompetes most existing cloning methods in simplicity and affordability
      and is well-suited for high-throughput applications. 

PMID- 25370828
TI  - Fascin-1 as a biomarker and prospective therapeutic target in colorectal cancer.
AB  - Fascin-1 is a filamentous actin-binding protein that crosslinks actin
      microfilaments into tight, parallel bundles. These bundles are important for the
      extension of microspikes, filopodia and invadopodia from cell surfaces and for
      the functionality of these protrusions in cell migration and/or dynamic sensing
      of the local microenvironment. Fascin-1 is absent in normal colonic epithelium,
      but its upregulation in colorectal adenomas and adenocarcinomas and its
      correlation with an aggressive clinical course has piqued the interest of many
      laboratories with research interests in cancer metastasis. This report summarizes
      current knowledge of the molecular interactions of fascin-1 in relation to its
      activities and mechanisms of upregulation in colorectal carcinoma cells. The
      status and key questions surrounding investigations of fascin-1 as a novel, early
      prognostic biomarker in colorectal cancer are discussed. Ongoing pre-clinical
      research into new migration inhibitory and anti-metastatic compounds that alter
      the actin cytoskeleton, and the goal of targeting fascin-1, is also discussed. 

PMID- 25370827
TI  - Identification of functional regions in the Rhodospirillum rubrum L-asparaginase
      by site-directed mutagenesis.
AB  - Site-directed mutagenesis of Rhodospirillum rubrum L-asparaginase (RrA) was
      performed in order to identify sites of the protein molecule important for its
      therapeutic and physico-chemical properties. Ten multipoint mutant genes were
      obtained, and five recombinant RrA variants were expressed in E. coli BL21(DE3)
      cells and isolated as functionally active highly purified proteins. Protein
      purification was performed using Q-Sepharose and DEAE-Toyopearl chromatography.
      Overall yield of the active enzymes was 70-80 %, their specific activity at pH
      7.4 and 37  degrees C varied of 140-210 U/mg. L-Glutaminase activity did not
      exceed 0.01 % of L-asparaginase activity. All RrA mutants showed maximum enzyme
      activity at pH 9.3-9.5 and 53-58  degrees C. Km and Vmax values for L-asparagine
      were evaluated for all mutants. Mutations G86P, D88H, M90K (RrAH), G121L, D123A
      (RrAI) caused the loss of enzyme activity and confirmed the importance of these
      sites in the implementation of catalytic functions. Removal of four residues from
      C-terminal area of the enzyme (RrAK) resulted in the enzyme instability.
      Mutations D60K, F61L(RrAD), and R118H, G120R(RrAJ) led to the improvement of
      kinetic parameters and enzyme stabilization. Substitutions E149R, V150P (RrAB)
      improved antineoplastic and cytotoxic activity of the RrA. A64V, E67K
      substitutions, especially in combination with E149R, V150P (RrAE), considerably
      destabilized recombinant enzyme.

PMID- 25370829
TI  - Efficient synthesis of pi-extended phenazasilines for optical and electronic
      applications.
AB  - The rhodium-catalyzed synthesis of phenazasilines from readily achievable
      biarylhydrosilanes is presented. This highly efficient method offers
      opportunities for preparing pi-extended phenazasilines with enhanced
      optoelectronic properties for device applications in organic electronics. 

PMID- 25370830
TI  - Synthesis, properties, and redox behavior of 1,1,4,4-tetracyano-2-ferrocenyl-1,3
      butadienes connected by aryl, biaryl, and teraryl spacers.
AB  - Aryl-substituted 1,1,4,4-tetracyano-1,3-butadienes (FcTCBDs) and bis(1,1,4,4
      tetracyanobutadiene)s (bis-FcTCBDs), possessing a ferrocenyl group on each
      terminal, were prepared by the reaction of a variety of alkynes with
      tetracyanoethylene (TCNE) in a [2+2] cycloaddition reaction, followed by retro
      electrocyclization of the initially formed [2+2] cycloadducts (i.e., cyclobutene
      derivatives). The characteristic intramolecular charge transfer (ICT) between the
      donor (ferrocene) and acceptor (TCBD) moieties were investigated by using UV/Vis
      spectroscopy. The redox behaviors of FcTCBDs and bis-FcTCBDs were examined by
      cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed
      their properties of multi-electron transfer depending on the number of ferrocene
      and TCBD moieties. Moreover, significant color changes were observed by visible
      spectroscopy under the electrochemical reduction conditions. 

PMID- 25370831
TI  - Heterozygosity at a single locus explains a large proportion of variation in two
      fitness-related traits in great tits: a general or a local effect?
AB  - In natural populations, mating between relatives can have important fitness
      consequences due to the negative effects of reduced heterozygosity. Parental
      level of inbreeding or heterozygosity has been also found to influence the
      performance of offspring, via direct and indirect parental effects that are
      independent of the progeny own level of genetic diversity. In this study, we
      first analysed the effects of parental heterozygosity and relatedness (i.e. an
      estimate of offspring genetic diversity) on four traits related to offspring
      viability in great tits (Parus major) using 15 microsatellite markers. Second, we
      tested whether significant heterozygosity-fitness correlations (HFCs) were due to
      'local' (i.e. linkage to genes influencing fitness) and/or 'general' (genome-wide
      heterozygosity) effects. We found a significant negative relationship between
      parental genetic relatedness and hatching success, and maternal heterozygosity
      was positively associated with offspring body size. The characteristics of the
      studied populations (recent admixture, polygynous matings) together with the fact
      that we found evidence for identity disequilibrium across our set of neutral
      markers suggest that HFCs may have resulted from genome-wide inbreeding
      depression. However, one locus (Ase18) had disproportionately large effects on
      the observed HFCs: heterozygosity at this locus had significant positive effects
      on hatching success and offspring size. It suggests that this marker may lie near
      to a functional locus under selection (i.e. a local effect) or, alternatively,
      heterozygosity at this locus might be correlated to heterozygosity across the
      genome due to the extensive ID found in our populations (i.e. a general effect).
      Collectively, our results lend support to both the general and local effect
      hypotheses and reinforce the view that HFCs lie on a continuum from inbreeding
      depression to those strictly due to linkage between marker loci and genes under
      selection. 

PMID- 25370832
TI  - A synthetic strategy for switching the single ion anisotropy in tetrahedral
      Co(II) complexes.
AB  - Four novel mononuclear tetrahedral cobalt(II) complexes containing exocyclic
      mesoionic ligands of molecular formulae [Co(II)(L1)(X)2(MeCN)] X = Cl (1) or Br
      (2) and [Co(II)(L2)(X)2(MeCN)], X = Cl (3) or Br (4) have been reported. It is
      found that simple substitution of L1 (O donor in 1 and 2) by L2 (S donor in 3 and
      4) results in switching of the single ion magnetic anisotropy parameter (D) from
      positive to negative, with a significant change in magnitude.

PMID- 25370833
TI  - Angiopoietin-like protein 2 induces androgen-independent and malignant behavior
      in human prostate cancer cells.
AB  - Angiopoietin-like proteins (ANGPTLs), which comprise 7 members (ANGPTL1-ANGPTL7),
      structurally resemble angiopoietins. We investigated the roles of ANGPTLs in the
      acquisition of androgen independence and the malignant behavior of human prostate
      cancer cells. Expression of ANGPTL messenger RNA (mRNA) and proteins were
      ascertained using RT-qPCR and western blot analysis in human prostate cancer cell
      lines. Androgen-dependent LNCaP and androgen-independent LNCaP/AI cells,
      respectively, were cultured in fetal bovine and charcoal-stripped medium. Cell
      proliferation, androgen dependence, migration and invasion, respectively, were
      examined under the overexpression and knockdown of ANGPTL2 by transfection of
      ANGPTL2 cDNA and its small-interfering RNA (siRNA). The effects of exogenous
      ANGPTL2 and blocking of its receptor, integrin alpha5beta1, were also
      investigated. Human prostate cancer cell lines predominantly expressed ANGPTL2
      among the members. Interrupting ANGPTL2 expression with siRNA suppressed the
      proliferation, migration and invasion of LNCaP cells. LNCaP/AI cells showed a
      higher ANGPTL2 expression than that of LNCaP cells. Furthermore, siRNA led to
      apoptosis of LNCaP/AI cells. The ANGPTL2-overexpressing LNCaP cells markedly
      increased proliferation, epithelial-to-mesenchymal transition (EMT) and malignant
      behavior in androgen-deprived medium. The migration rates were increased
      depending on the concentration of ANGPTL2 recombinant protein and were inhibited
      by anti-integrin alpha5beta1 antibodies. To the best of our knowledge, this is
      the first study to elucidate the expression of ANGPTL2 in human prostate cancer
      cells. ANGPTL2 may be important in the acquisition of androgen independency and
      tumor progression of prostate cancer in an autocrine and/or paracrine manner via
      the integrin alpha5beta1 receptor. Targeting ANGPTL2 may therefore be an
      efficacious therapeutic modality for prostate cancer.

PMID- 25370834
TI  - Quantum yield and excitation rate of single molecules close to metallic
      nanostructures.
AB  - The interaction of dyes and metallic nanostructures strongly affects the
      fluorescence and can lead to significant fluorescence enhancement at plasmonic
      hot spots, but also to quenching. Here we present a method to distinguish the
      individual contributions to the changes of the excitation, radiative and non
      radiative rate and use this information to determine the quantum yields for
      single molecules. The method is validated by precisely placing single fluorescent
      dyes with respect to gold nanoparticles as well as with respect to the excitation
      polarization using DNA origami nanostructures. Following validation, measurements
      in zeromode waveguides reveal that suppression of the radiative rate and
      enhancement of the non-radiative rate lead to a reduced quantum yield. Because
      the method exploits the intrinsic blinking of dyes, it can generally be applied
      to fluorescence measurements in arbitrary nanophotonic environments. 

PMID- 25370835
TI  - Integrin alphav promotes proliferation by activating ERK 1/2 in the human lung
      cancer cell line A549.
AB  - Lung cancer is a leading cause of cancer-related death worldwide, and non-small
      cell lung cancer (NSCLC) constitutes ~85% of lung cancers. However, the
      mechanisms underlying the progression of NSCLC remain unclear. In this study, we
      found the mRNA and protein expression levels of integrin alphav are both
      increased in NSCLC tissues compared to healthy ones, which indicates that
      integrin alphav may play an important role in NSCLC progression. To further
      investigate the roles of integrin alphav in NSCLC, we overexpressed the integrin
      alphav gene in the NSCLC cell line A549, and found that the cell proliferative
      ability increased. The apoptosis of A549 cells was inhibited with overexpression
      of integrin alphav. To elucidate the molecular mechanism underlying the role of
      integrin alphav in promoting NSCLC progression, we studied the expression of
      proteins from a number of important pathways associated with tumorigenesis, and
      found that the extracellular signal regulated protein kinase (ERK)1/2 signaling
      pathway may be involved in the mediation of the observed integrin alphav effects.
      component of an important pathway for tumorigenesis, the ERK 1/2. Following
      inhibition of ERK 1/2 signaling, the proliferation of A549 cells induced by
      integrin alphav was reduced, while the inhibition of apoptosis was attenuated.
      Our findings demonstrate that integrin alphav promotes the proliferation of the
      human lung cancer cell line A549 by activating the ERK 1/2 signaling pathway,
      which suggests that this pathway may be a promising target for the treatment of
      human lung cancer.

PMID- 25370836
TI  - Comparative analyses of Legionella species identifies genetic features of strains
      causing Legionnaires' disease.
AB  - BACKGROUND: The genus Legionella comprises over 60 species. However, L.
      pneumophila and L. longbeachae alone cause over 95% of Legionnaires' disease. To
      identify the genetic bases underlying the different capacities to cause disease
      we sequenced and compared the genomes of L. micdadei, L. hackeliae and L.
      fallonii (LLAP10), which are all rarely isolated from humans. RESULTS: We show
      that these Legionella species possess different virulence capacities in amoeba
      and macrophages, correlating with their occurrence in humans. Our comparative
      analysis of 11 Legionella genomes belonging to five species reveals highly
      heterogeneous genome content with over 60% representing species-specific genes;
      these comprise a complete prophage in L. micdadei, the first ever identified in a
      Legionella genome. Mobile elements are abundant in Legionella genomes; many
      encode type IV secretion systems for conjugative transfer, pointing to their
      importance for adaptation of the genus. The Dot/Icm secretion system is
      conserved, although the core set of substrates is small, as only 24 out of over
      300 described Dot/Icm effector genes are present in all Legionella species. We
      also identified new eukaryotic motifs including thaumatin, synaptobrevin or
      clathrin/coatomer adaptine like domains. CONCLUSIONS: Legionella genomes are
      highly dynamic due to a large mobilome mainly comprising type IV secretion
      systems, while a minority of core substrates is shared among the diverse species.
      Eukaryotic like proteins and motifs remain a hallmark of the genus Legionella.
      Key factors such as proteins involved in oxygen binding, iron storage, host
      membrane transport and certain Dot/Icm substrates are specific features of
      disease-related strains.

PMID- 25370837
TI  - Role of IGF1-(CA)19 promoter microsatellite in the clinical presentation of
      acromegaly.
AB  - BACKGROUND: A highly polymorphic Cytosine-Adenosine (CA) repeat sequence
      microsatellite has been identified in the promoter region of IGF1 gene. Several
      studies investigated the relationship between IGF1-(CA)n polymorphism and IGF1
      levels, with conflicting results. Aim of this study was to investigate the
      influence of this polymorphism on clinical and biochemical characteristics of
      acromegalic patients. METHODS: Eighty-eight acromegalic patients and 104 normal
      subjects were included in the study. Blood DNA was extracted and analysed by
      microsatellite technique using capillary electrophoresis. Patients and controls
      were subdivided in 19/19 [homozygous for the (CA)19 allele], 19/X [heterozygous
      for the (CA)19 allele] and X/X (any other genotype). RESULTS: The genotype
      frequency was significantly different between patients and controls, the
      proportion of 19/19 being lower (28.4% vs. 50.0%) and 19/X and X/X higher in
      acromegalic patients than in controls (P = 0.004). There were no significant
      differences in age, gender, basal and nadir GH, IGF1-SDS, tumour size, metabolic
      parameters, outcome and treatment among the three groups. The different frequency
      of genotypes in acromegalic patients vs. controls, as well as the lack of
      relationship between IGF1-(CA)n polymorphism and clinical and biochemical data in
      acromegalic patients, was confirmed using an additional alternative genotyping
      considering (CA)19 and (CA)20 homozygotes and heterozygotes vs. alleles with more
      than 19 of 20 repeats or less. CONCLUSIONS: Our results do not support the
      hypothesis that IGF-(CA)n alleles may have a significant role in determining
      clinical, biochemical and outcome of patients with acromegaly. The possible role
      of IGF1 polymorphism on susceptibility to acromegaly remains to be investigated.

PMID- 25370838
TI  - Alberta Breakthrough Pain Assessment Tool: A validation multicentre study in
      cancer patients with breakthrough pain.
AB  - BACKGROUND: Cancer-related breakthrough pain (BTP) is a common and quite
      challenging pain syndrome, with significant impact on quality of life. To date,
      no widely recognized and validated tool for the diagnosis and evaluation of BTP
      exists. The Alberta Breakthrough Pain Assessment Tool (ABPAT) underwent a
      validation process during its development, but no experience of its
      implementation in clinical practice has been reported. METHODS: ABPAT was tested
      in a cohort of cancer patients suffering from chronic severe cancer-related pain
      in order to assess its acceptability and efficacy as a tool for the
      characterization of BTP. RESULTS: A total of consecutive 249 patients from seven
      different centres were included in a 2-month study period and all completed the
      questionnaire; 231 out of the 249 (92.8%) stated that questions were easily
      understandable and 217 out of the 249 (87.1%) stated that the tool allowed to
      explain extensively the BTP problem. Physician-patient correlation tests about
      baseline BTP intensity and BTP relief by medication showed statistical
      significance at the level of p = 0.001 and p = 0.0001, respectively. Evaluation
      of the efficacy of BPT medication revealed a 78.2% of patients declaring a good
      relief from BTP, with a significant reduction of mean BTP numeric rating scale
      score (p = 0.0001), but only 55.9% of patients responded to be satisfied about
      time for onset of the relief. CONCLUSIONS: In this study, ABPAT resulted to be a
      well-accepted tool for BTP assessment and characterization in a relatively large
      cohort of cancer patients. It is effective in discovering the unmet needs of
      cancer patients and in exploring the outcomes of BTP treatment.

PMID- 25370839
TI  - Student Accomplishments in the Rapid Response Radiotherapy Program: A 10-Year
      Review.
AB  - In 1996, the Toronto Sunnybrook Regional Cancer Centre developed the Rapid
      Response Radiotherapy Program (RRRP). The objective of this clinic is to consult,
      simulate, plan, and treat patients with palliative radiotherapy on the same day.
      In 2004, the RRRP initiated a program to provide clinical and research experience
      to undergraduate students interested in health sciences. The purpose of this
      study is to review the 10-year (2004-2013) experience of the RRRP and to examine
      whether the goals of the student program have been met. Students who worked in
      the RRRP from 2004 to 2013 were contacted to complete a short survey regarding
      their overall experience with the program and their current endeavors. Student
      accomplishments were collected from an internal database as well as PubMed.
      Descriptive statistics were used to analyze results. A total of 54 students from
      ten postsecondary institutions have worked in the RRRP; 29 were from the
      University of Waterloo undergraduate co-op program. In total, 214 articles with
      first authorship from students were published, 93 (43%) of which can be found on
      PubMed. Other accomplishments include 40 book chapters, 58 invited presentations,
      and 99 awards cumulatively. Qualitative data regarding student perspectives of
      their experience in the RRRP were also analyzed. Over the past 10 years, the RRRP
      has achieved its goal of providing quality medical and research experience to
      students interested in the health sciences. Using the responses of past and
      present students, we hope to continue to shape our program and provide unique
      opportunities to future students.

PMID- 25370840
TI  - Increased micronucleus, nucleoplasmic bridge, and nuclear bud frequencies in the
      peripheral blood lymphocytes of diesel engine exhaust-exposed workers.
AB  - The International Agency for Research on Cancer has recently reclassified diesel
      engine exhaust (DEE) as a Group 1 carcinogen. Micronucleus (MN), nucleoplasmic
      bridge (NPB), and nuclear bud (NBUD) frequencies in peripheral blood lymphocytes
      (PBLs) are associated with cancer risk. However, the impact of DEE exposure on MN
      frequency has not been thoroughly elucidated due to mixed exposure and its impact
      on NPB and NBUD frequencies has never been explored in humans. We recruited 117
      diesel engine testing workers with exclusive exposure to DEE and 112 non-DEE
      exposed workers, and then we measured urinary levels of 4 mono-hydroxylated
      polycyclic aromatic hydrocarbons (OH-PAHs) using high-performance liquid
      chromatography-mass spectrometry as well as MN, NPB, and NBUD frequencies in PBLs
      using cytokinesis-block MN assay. The DEE-exposed workers exhibited significantly
      higher MN, NPB, and NBUD frequencies than the non-DEE-exposed workers (P < 0.05).
      Among all study subjects, increasing levels of all 4 urinary OH-PAHs, on both
      quartile and continuous scales, were associated with increased MN, NPB, and NBUD
      frequencies (all P < 0.05). When the associations were analyzed separately in DEE
      exposed and non-DEE-exposed workers, we found that the association between
      increasing quartiles of urinary 9-hydroxyphenanthrene (9-OHPh) and MN frequencies
      persisted in DEE-exposed workers (P = 0.001). The percent of MN frequencies
      increased, on average, by 23.99% (95% confidential interval, 9.64-39.93) per 1
      unit increase in ln-transformed 9-OHPh. Our results clearly show that exposure to
      DEE can induce increases in MN, NPB, and NBUD frequencies in PBLs and suggest
      that DEE exposure level is associated with MN frequencies.

PMID- 25370841
TI  - Downregulation of stanniocalcin 1 is responsible for sorafenib-induced
      cardiotoxicity.
AB  - Sorafenib is associated with adverse cardiac effects, including left ventricular
      dysfunction. However, the precise mechanism remains unclear. Here, we aimed to
      establish the genes responsible for this cardiotoxicity using zebrafish and human
      cardiomyocytes. Fluorescent cardiac imaging using pigmentless zebrafish with
      green fluorescent protein hearts revealed that the ventricular dimensions of the
      longitudinal axis with sorafenib were significantly shorter than those of the
      control group. Transcriptome analysis of their hearts revealed that stanniocalcin
      1 (stc1) was downregulated by sorafenib. stc1 knockdown in zebrafish revealed
      that reduction of stc1 decreased the longitudinal dimensions of zebrafish
      ventricles, similar to that which occurs during sorafenib treatment. STC1
      downregulation and cytotoxicity were also seen in human cardiomyocytes exposed to
      sorafenib. To clarify the molecular function of stc1 in sorafenib-induced
      cardiotoxicity, we focused on oxidative stress in cardiomyocytes treated with
      sorafenib. Reactive oxygen species (ROS) production significantly increased in
      both species of human cardiomyocytes and zebrafish exposed to sorafenib and STC1
      knockdown compared with the controls. Finally, we found that forced expression of
      stc1 normalized impairment, decreasing the longitudinal dimensions in zebrafish
      treated with sorafenib. Our study demonstrated that STC1 plays a protective role
      against ventricular dysfunction and ROS overproduction, which are induced by
      sorafenib treatment. We discovered for the first time that STC1 downregulation is
      responsible for sorafenib-induced cardiotoxicity through activated ROS
      generation. 

PMID- 25370843
TI  - Power and color Doppler ultrasound settings for inflammatory flow: impact on
      scoring of disease activity in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine how settings for power and color Doppler ultrasound
      sensitivity vary on different high- and intermediate-range ultrasound machines
      and to evaluate the impact of these changes on Doppler scoring of inflamed
      joints. METHODS: Six different types of ultrasound machines were used. On each
      machine, the factory setting for superficial musculoskeletal scanning was used
      unchanged for both color and power Doppler modalities. The settings were then
      adjusted for increased Doppler sensitivity, and these settings were designated
      study settings. Eleven patients with rheumatoid arthritis (RA) with wrist
      involvement were scanned on the 6 machines, each with 4 settings, generating 264
      Doppler images for scoring and color quantification. Doppler sensitivity was
      measured with a quantitative assessment of Doppler activity: color fraction.
      Higher color fraction indicated higher sensitivity. RESULTS: Power Doppler was
      more sensitive on half of the machines, whereas color Doppler was more sensitive
      on the other half, using both factory settings and study settings. There was an
      average increase in Doppler sensitivity, despite modality, of 78% when study
      settings were applied. Over the 6 machines, 2 Doppler modalities, and 2 settings,
      the grades for each of 7 of the patients varied between 0 and 3, while the grades
      for each of the other 4 patients varied between 0 and 2. CONCLUSION: The effect
      of using different machines, Doppler modalities, and settings has a considerable
      influence on the quantification of inflammation by ultrasound in RA patients, and
      this must be taken into account in multicenter studies.

PMID- 25370844
TI  - Nasal septal haematoma.

PMID- 25370842
TI  - Vesicular monoamine transporter 2 and the acute and long-term response to 3,4-(+/
      )-methylenedioxymethamphetamine.
AB  - 3,4-(+/-)-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a ring-substituted
      amphetamine derivative with potent psychostimulant properties. The
      neuropharmacological effects of MDMA are biphasic in nature, initially causing
      synaptic monoamine release, primarily of serotonin (5-HT). Conversely, the long
      term effects of MDMA manifest as prolonged depletions in 5-HT, and reductions in
      5-HT reuptake transporter (SERT), indicative of serotonergic neurotoxicity. MDMA
      induced 5-HT efflux relies upon disruption of vesicular monoamine storage, which
      increases cytosolic 5-HT concentrations available for release via a carrier
      mediated mechanism. The vesicular monoamine transporter 2 (VMAT2) is responsible
      for packaging monoamine neurotransmitters into cytosolic vesicles. Thus, VMAT2 is
      a molecular target for a number of psychostimulant drugs, including
      methamphetamine and MDMA. We investigated the effects of depressed VMAT2 activity
      on the adverse responses to MDMA, via reversible inhibition of the VMAT2 protein
      with Ro4-1284. A single dose of MDMA (20 mg/kg, subcutaneous) induced significant
      hyperthermia in rats. Ro4-1284 (10 mg/kg, intraperitoneal) pretreatment prevented
      the thermogenic effects of MDMA, instead causing a transient decrease in body
      temperature. MDMA-treated rats exhibited marked increases in horizontal velocity
      and rearing behavior. In the presence of Ro4-1284, MDMA-mediated horizontal
      hyperlocomotion was delayed and attenuated, whereas rearing activity was
      abolished. Finally, Ro4-1284 prevented deficits in 5-HT content in rat cortex and
      striatum, and reduced depletions in striatal SERT staining, 7 days after MDMA
      administration. In summary, acute inhibition of VMAT2 by Ro4-1284 protected
      against MDMA-mediated hyperthermia, hyperactivity, and serotonergic
      neurotoxicity. The data suggest the involvement of VMAT2 in the thermoregulatory,
      behavioral, and neurotoxic effects of MDMA. 

PMID- 25370845
TI  - A collapse with hypertension and hypokalaemia.

PMID- 25370846
TI  - US trade rep is pressing Indian government to forbid production of generic cancer
      drug, consortium says.

PMID- 25370847
TI  - Private member's bill aims to repeal competition rules in NHS.

PMID- 25370848
TI  - Endothelin as a local regulating factor in the bovine oviduct.
AB  - Endothelin (EDN) is a possible regulating factor of oviductal motility, which is
      important for the transport of gametes and embryo. To clarify the factors that
      control the secretion of EDN in the bovine oviduct, the expression of EDNs, EDN
      converting enzymes (ECEs) and EDN receptors (EDNRs) were investigated. All
      isoforms of EDN (EDN1-3), ECE (ECE1 and ECE2) and EDNR (EDNRA and EDNRB) were
      immunolocalised in the epithelial cells of the ampulla and the isthmus. EDNRs
      were also immunolocalised in smooth-muscle cells. The mRNA expression of EDN2 and
      ECE2 was higher in cultured ampullary oviductal epithelial cells than in isthmic
      cells. The expression of EDN1, EDN2 and ECE2 in the ampullary tissue was highest
      on the day of ovulation. Oestradiol-17beta increased EDN2 and ECE1 expression,
      while progesterone increased only ECE1 expression in cultured ampullary
      epithelial cells. These results indicate that EDNs are produced by epithelial
      cells and their target site is smooth-muscle and epithelial cells, and suggest
      that ovarian steroids are regulators of endothelin synthesis in ampullary
      oviductal epithelial cells. 

PMID- 25370849
TI  - Active vitamin D deficiency mediated by extracellular calcium and phosphorus
      results in male infertility in young mice.
AB  - We used mice with targeted deletion of 25-hydroxyvitamin D-1 alpha-hydroxylase
      [1alpha(OH)ase(-/-)] to investigate whether 1,25(OH)2D3 deficiency results in
      male infertility mediated by 1,25(OH)2D3 or extracellular calcium and phosphorus.
      Male 1alpha(OH)ase(-/-) and their wild-type littermates fed either a normal diet
      or a rescue diet from weaning were mated at 6-14 wk of age with female wild-type
      mice on the same diet. The fertility efficiency of females was analyzed, and the
      reproductive phenotypes of males were evaluated by histopathological and
      molecular techniques. Hypocalcemic and hypophosphatemic male 1alpha(OH)ase(-/-)
      mice on a normal diet developed infertility characterized by hypergonadotropic
      hypogonadism, with downregulation of testicular calcium channels, lower
      intracellular calcium levels, decreased sperm count and motility, and
      histological abnormalities of the testes. The proliferation of spermatogenic
      cells was decreased with downregulation of cyclin E and CDK2 and upregulation of
      p53 and p21 expression, whereas apoptosis of spermatogenic cells was increased
      with upregulation of Bax and p-caspase 3 expression and downregulation of Bcl-xl
      expression. When serum calcium and phosphorus were normalized by the rescue diet,
      the defective reproductive phenotype in the male 1alpha(OH)ase(-/-) mice,
      including the hypergonadotropic hypogonadism, decreased sperm count and motility,
      histological abnormalities of testis, and defective spermatogenesis, was
      reversed. These results indicate that the infertility seen in male 1,25(OH)2D3
      deficient mice is not a direct effect of active vitamin D deficiency on the
      reproductive system but is an indirect effect mediated by extracellular calcium
      and phosphorus. 

PMID- 25370850
TI  - p38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells
      from insulin-resistant type 2 diabetic patients.
AB  - Skeletal muscle is the key site of peripheral insulin resistance in type 2
      diabetes. Insulin-stimulated glucose uptake is decreased in differentiated
      diabetic cultured myotubes, which is in keeping with a retained
      genetic/epigenetic defect of insulin action. We investigated differences in gene
      expression during differentiation between diabetic and control muscle cell
      cultures. Microarray analysis was performed using skeletal muscle cell cultures
      established from type 2 diabetic patients with a family history of type 2
      diabetes and clinical evidence of marked insulin resistance and nondiabetic
      control subjects with no family history of diabetes. Genes and pathways
      upregulated with differentiation in the diabetic cultures, compared with
      controls, were identified using Gene Spring and Gene Set Enrichment Analysis.
      Gene sets upregulated in diabetic myotubes were associated predominantly with
      inflammation. p38 MAPK was identified as a key regulator of the expression of
      these proinflammatory gene sets, and p38 MAPK activation was found to be
      increased in the diabetic vs. control myotubes. Although inhibition of p38 MAPK
      activity decreased cytokine gene expression from the cultured diabetic myotubes
      significantly, it did not improve insulin-stimulated glucose uptake. Increased
      cytokine expression driven by increased p38 MAPK activation is a key feature of
      cultured myotubes derived from insulin-resistant type 2 diabetic patients. p38
      MAPK inhibition decreased cytokine expression but did not affect the retained
      defect of impaired insulin action in the diabetic muscle cells. 

PMID- 25370851
TI  - Inhibition of secreted frizzled-related protein 5 improves glucose metabolism.
AB  - Elucidating the role of secreted frizzled-related protein 5 (SFRP5) in metabolism
      and obesity has been complicated by contradictory findings when knockout mice
      were used to determine metabolic phenotypes. By overexpressing SFRP5 in obese,
      prediabetic mice we consistently observed elevated hyperglycemia and glucose
      intolerance, supporting SFRP5 as a negative regulator of glucose metabolism.
      Accordingly, Sfrp5 mRNA expression analysis of both epididymal and subcutaneous
      adipose depots of mice indicated a correlation with obesity. Thus, we generated a
      monoclonal antibody (mAb) against SFRP5 to ascertain the effect of SFRP5
      inhibition in vivo. Congruent with SFRP5 overexpression worsening blood glucose
      levels and glucose intolerance, anti-SFRP5 mAb therapy improved these phenotypes
      in vivo. The results from both the overexpression and mAb inhibition studies
      suggest a role for SFRP5 in glucose metabolism and pancreatic beta-cell function
      and thus establish the use of an anti-SFRP5 mAb as a potential approach to treat
      type 2 diabetes. 

PMID- 25370852
TI  - MAP kinase phosphatase DUSP1 is overexpressed in obese humans and modulated by
      physical exercise.
AB  - Chronic low-grade inflammation and dysregulation of the stress defense system are
      cardinal features of obesity, a major risk factor for the development of insulin
      resistance and diabetes. Dual-specificity protein phosphatase 1 (DUSP1), known
      also as MAP kinase phosphatase 1 (MKP1), is implicated in metabolism and energy
      expenditure. Mice lacking DUSP1 are resistant to high-fat diet-induced obesity.
      However, the expression of DUSP1 has not been investigated in human obesity. In
      the current study, we compared the expression pattern of DUSP1 between lean and
      obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and
      peripheral blood mononuclear cells (PBMCs). The levels of DUSP1 mRNA and protein
      were significantly increased in obese subjects with concomitant decrease in the
      phosphorylation of p38 MAPK (p-p38 MAPK) and PGC-1alpha and an increase in the
      levels of phospho-JNK (p-JNK) and phospho-ERK (p-ERK). Moreover, obese subjects
      had higher levels of circulating DUSP1 protein that correlated positively with
      various obesity indicators, triglycerides, glucagon, insulin, leptin, and PAI-1
      (P < 0.05) but negatively with VO(2max) and high-density lipoprotein (P < 0.05).
      The observation that DUSP1 was overexpressed in obese subjects prompted us to
      investigate whether physical exercise could reduce its expression. In this study,
      we report for the first time that physical exercise significantly attenuated the
      expression of DUSP1 in both the SAT and PBMCs, with a parallel increase in the
      expression of PGC-1alpha and a reduction in the levels of p-JNK and p-ERK along
      with attenuated inflammatory response. Collectively, our data suggest that DUSP1
      upregulation is strongly linked to adiposity and that physical exercise modulates
      its expression. This gives further evidence that exercise might be useful as a
      strategy for managing obesity and preventing its associated complications.

PMID- 25370853
TI  - Adjusting the starting dose of telaprevir according to renal function decreases
      adverse effects and affects the sustained virological response rate.
AB  - BACKGROUND: Telaprevir (TVR) plays a major role in renal damage and anemia
      associated with TVR/pegylated interferon/ribavirin therapy for chronic hepatitis
      C. Adjusting the TVR starting dose may reduce these adverse effects. We aimed to
      determine whether adjusting the starting dose according to renal function reduces
      TVR-associated renal damage and anemia and affects the sustained virological
      response (SVR). PATIENTS AND METHODS: Our study included 112 patients infected
      with hepatitis C genotype 1 treated with pegylated interferon/ribavirin/TVR
      triple therapy. The TVR starting dose adjusted according to renal function was
      calculated as TVR/unadjusted estimated glomerular filtration rate (eGFR)
      ratio=TVR/(eGFR*body surface area/1.73). RESULTS: A TVR/unadjusted eGFR ratio of
      32 or greater was a predictor of renal impairment and anemia in multivariate
      analysis (odds ratio 12.09, P<0.001, and OR 4.14, P<0.001, respectively).
      Patients with a TVR/unadjusted eGFR ratio of 32 or greater developed significant
      renal impairment and anemia (P<0.001 and P=0.002, respectively). SVR was
      significantly reduced in patients with a TVR/unadjusted eGFR ratio less than 23
      versus 23 or greater (66.7 and 87.2%, respectively, P=0.045). SVR tended to
      increase stepwise [<23.0 (66.7%), >=23 to <32 (84.8%), and >=32 (89.6%),
      respectively]. The TVR/unadjusted eGFR ratio was correlated significantly with
      the serum TVR concentration (r=0.541, P<0.001). CONCLUSION: Adjusting the TVR
      starting dose according to the TVR/unadjusted eGFR ratio decreased adverse
      effects and affected the SVR rate. The TVR starting dose should be adjusted by a
      TVR/unadjusted eGFR ratio of 23 or greater to less than 32 to safely achieve SVR.

PMID- 25370854
TI  - Diagnostic confidence of computed tomography and magnetic resonance in focal
      liver pathology.
AB  - PURPOSE: The aim of this study was to evaluate and compare the diagnostic
      confidence of multiphase computed tomography (CT) and magnetic resonance (MR)
      after administration of gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic
      acid (Gd-EOB-DTPA) in the diagnosis of malignant-benign neoplasm of the liver in
      operators with different levels of experience. MATERIALS AND METHODS: Forty
      patients underwent multiphase CT and MR after administration of Gd-EOB-DTPA. All
      exams were evaluated by two experienced observers independently; they rated their
      diagnostic confidence on a five-degree scale: 1 (certainly benign), 2 (probably
      benign), 3 (uncertain), 4 (probably malignant) and 5 (certainly malignant).
      Receiver operating characteristic curve analysis and area under the curve (AUC)
      were carried out for each observer and their difference was tested according to
      the different methodologies used. RESULTS: In our population, there were 15
      malignant neoplasms and 25 benign neoplasms. For the CT analysis, AUC was 0.792
      [SE=0.088; 95% confidence interval (CI) 0.634-0.903] and 0.701 (SE=0.099; 95% CI
      0.535-0.835) for observers 1 and 2, respectively, whereas for the MR analysis,
      AUC was 0.923 (SE=0.058; 95% CI 0.793-0.983) and 0.934 (SE=0.054; 95% CI 0.808
      0.987). For both observers, a statistically significant difference was found in
      diagnostic confidence between the AUC of CT and MR (P<0.05). CONCLUSION: Our
      results indicate that, for expert and intermediate experience observers, the
      diagnostic confidence using MR with Gd-EOB-DTPA is statistically significantly
      superior to CT with a multiphase technique.

PMID- 25370855
TI  - Computerized Dose Range Checking Using Hard and Soft Stop Alerts Reduces
      Prescribing Errors in a Pediatric Intensive Care Unit.
AB  - OBJECTIVE: An enhanced dose range checking (DRC) system was developed to evaluate
      prescription error rates in the pediatric intensive care unit and the pediatric
      cardiovascular intensive care unit. METHODS: An enhanced DRC system incorporating
      "soft" and "hard" alerts was designed and implemented. Practitioner responses to
      alerts for patients admitted to the pediatric intensive care unit and the
      pediatric cardiovascular intensive care unit were retrospectively reviewed.
      RESULTS: Alert rates increased from 0.3% to 3.4% after "go-live" (P < 0.001).
      Before go-live, all alerts were soft alerts. In the period after go-live, 68% of
      alerts were soft alerts and 32% were hard alerts. Before go-live, providers
      reduced doses only 1 time for every 10 dose alerts. After implementation of the
      enhanced computerized physician order entry system, the practitioners responded
      to soft alerts by reducing doses to more appropriate levels in 24.7% of orders
      (70/283), compared with 10% (3/30) before go-live (P = 0.0701). The practitioners
      deleted orders in 9.5% of cases (27/283) after implementation of the enhanced DRC
      system, as compared with no cancelled orders before go-live (P = 0.0774).
      Medication orders that triggered a soft alert were submitted unmodified in 65.7%
      (186/283) as compared with 90% (27/30) of orders before go-live (P = 0.0067).
      After go-live, 28.7% of hard alerts resulted in a reduced dose, 64% resulted in a
      cancelled order, and 7.4% were submitted as written. CONCLUSIONS: Before go-live,
      alerts were often clinically irrelevant. After go-live, there was a statistically
      significant decrease in orders that were submitted unmodified and an increase in
      the number of orders that were reduced or cancelled.

PMID- 25370856
TI  - Automated reference region extraction and population-based input function for
      brain [(11)C]TMSX PET image analyses.
AB  - [(11)C]TMSX ([7-N-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7
      trimethylxanthine) is a selective adenosine A2A receptor (A2AR) radioligand. In
      the central nervous system (CNS), A2AR are linked to dopamine D2 receptor
      function in striatum, but they are also important modulators of inflammation. The
      golden standard for kinetic modeling of brain [(11)C]TMSX positron emission
      tomography (PET) is to obtain arterial input function via arterial blood
      sampling. However, this method is laborious, prone to errors and unpleasant for
      study subjects. The aim of this work was to evaluate alternative input function
      acquisition methods for brain [(11)C]TMSX PET imaging. First, a noninvasive,
      automated method for the extraction of gray matter reference region using
      supervised clustering (SCgm) was developed. Second, a method for obtaining a
      population-based arterial input function (PBIF) was implemented. These methods
      were created using data from 28 study subjects (7 healthy controls, 12 multiple
      sclerosis patients, and 9 patients with Parkinson's disease). The results with
      PBIF correlated well with original plasma input, and the SCgm yielded similar
      results compared with cerebellum as a reference region. The clustering method for
      extracting reference region and the population-based approach for acquiring input
      for dynamic [(11)C]TMSX brain PET image analyses appear to be feasible and robust
      methods, that can be applied in patients with CNS pathology. 

PMID- 25370857
TI  - Regulation of brain blood flow and oxygen delivery in elite breath-hold divers.
AB  - The roles of involuntary breathing movements (IBMs) and cerebral oxygen delivery
      in the tolerance to extreme hypoxemia displayed by elite breath-hold divers are
      unknown. Cerebral blood flow (CBF), arterial blood gases (ABGs), and
      cardiorespiratory metrics were measured during maximum dry apneas in elite breath
      hold divers (n=17). To isolate the effects of apnea and IBM from the concurrent
      changes on ABG, end-tidal forcing ('clamp') was then used to replicate an
      identical temporal pattern of decreasing arterial PO2 (PaO2) and increasing
      arterial PCO2 (PaCO2) while breathing. End-apnea PaO2 ranged from 23 to 37 mm Hg
      (30 +/- 7 mm Hg). Elevation in mean arterial pressure was greater during apnea
      than during clamp reaching +54 +/- 24% versus 34 +/- 26%, respectively; however,
      CBF increased similarly between apnea and clamp (93.6 +/- 28% and 83.4 +/- 38%,
      respectively). This latter observation indicates that during the overall apnea
      period IBM per se do not augment CBF and that the brain remains sufficiently
      protected against hypertension. Termination of apnea was not determined by
      reduced cerebral oxygen delivery; despite 40% to 50% reductions in arterial
      oxygen content, oxygen delivery was maintained by commensurately increased CBF.

PMID- 25370858
TI  - Enteral supplements of a carbon monoxide donor CORM-A1 protect against
      cerebrovascular dysfunction caused by neonatal seizures.
AB  - Cerebral blood flow dysregulation caused by oxidative stress contributes to
      adverse neurologic outcome of seizures. A carbon monoxide (CO) donor CORM-A1 has
      antioxidant and cytoprotective properties. We investigated whether enteral
      supplements of CORM-A1 can improve cerebrovascular outcome of bicuculline-induced
      seizures in newborn piglets. CORM-A1 (2 mg/kg) was given to piglets via an oral
      gastric tube 10 minutes before or 20 minutes after seizure onset. Enteral CORM-A1
      elevated CO in periarachnoid cerebrospinal fluid and produced a dilation of pial
      arterioles. Postictal cerebral vascular responses to endothelium-, astrocyte-,
      and vascular smooth muscle-dependent vasodilators were tested 48 hours after
      seizures by intravital microscopy. The postictal responses of pial arterioles to
      bradykinin, glutamate, the AMPA receptor agonist quisqualic acid, ADP, and heme
      were greatly reduced, suggesting that seizures cause injury to endothelial and
      astrocyte components of the neurovascular unit. In contrast, in the two groups of
      piglets receiving enteral CORM-A1, the postictal cerebral vascular responsiveness
      to these dilators was improved. Overall, enteral supplements of CORM-A1 before or
      during seizures offer a novel effective therapeutic option to deliver
      cytoprotective mediator CO to the brain, reduce injury to endothelial and
      astrocyte components of cerebral blood flow regulation and to improve the
      cerebrovascular outcome of neonatal seizures.

PMID- 25370859
TI  - Predictive value of the velocity of collateral filling in patients with acute
      ischemic stroke.
AB  - The velocity of collateral filling can be assessed in dynamic time-resolved
      computed tomography (CT) angiographies and may predict initial CT perfusion (CTP)
      and follow-up lesion size. We included all patients with an M1+/- internal
      carotid artery (ICA) occlusion and follow-up imaging from an existing cohort of
      1791 consecutive patients who underwent multimodal CT for suspected stroke. The
      velocity of collateral filling was quantified using the delay of time-to-peak
      (TTP) enhancement of the M2 segment distal to the occlusion. Cerebral blood
      volume (CBV) and mean transit time (MTT)-CBV mismatch were assessed in initial
      CTP. Follow-up lesion size was assessed by magnetic resonance imaging (MRI) or
      non-enhanced CT (NECT). Multivariate analyses were performed to adjust for extent
      of collateralization and type of treatment. Our study comprised 116 patients.
      Multivariate analysis showed a short collateral blood flow delay to be an
      independent predictor of a small CBV lesion (P<0.001) and a large relative
      mismatch (P<0.001) on initial CTP, of a small follow-up lesion (P<0.001), and of
      a small difference between initial CBV and follow-up lesion size (P=0.024). Other
      independent predictors of a small lesion on follow-up were a high morphologic
      collateral grade (P=0.001), lack of an additional ICA occlusion (P=0.009), and
      intravenous thrombolysis (P=0.022). Fast filling of collaterals predicts initial
      CTP and follow-up lesion size and is independent of extent of collateralization. 

PMID- 25370860
TI  - Noninvasive blood-free full quantification of positron emission tomography
      radioligand binding.
AB  - Full quantification of a positron emission tomography (PET) radioligand binding
      to its target is preferred because it requires the fewest assumptions, but
      generally involves measuring the concentration of free radioligand in the
      arterial plasma by collecting blood samples from the subject's radial artery
      during the scan, and performing metabolite analysis. This invasive, costly
      procedure deters subjects' participation, and requires specialized staff and
      equipment. Simultaneous estimation (SIME) can fully quantify binding using only
      PET data from multiple brain regions and one individual anchor value, which is
      based on a single arterial blood sample. Drawing this sample can still be
      challenging in clinical settings, particularly when using simultaneous
      PET/magnetic resonance scanners. Here we propose a methodology for full
      quantification of binding that does not require any blood samples. The
      methodology substitutes the SIME blood-based anchor with a value predicted using
      multiple linear regression of noninvasive, easy-to-collect variables related to
      the radioligand blood concentration, and individual metabolism, such as injected
      dose, body mass index, or body surface area. As a study case, we show here the
      methodology in comparison to analysis with full arterial-line blood sampling in a
      cohort of 23 available scans with [(11)C]CUMI-101, a partial agonist of the
      serotonin 5-HT1A receptors. 

PMID- 25370862
TI  - Head Injury in Children: Has a Change in Circumstances Caused an Increase in
      Treatment Numbers?
AB  - The number of hospitalizations for head injuries in children is rising. The exact
      causes remain unclear. We analyzed data of children aged between 0 and 18 years
      who sustained a head injury between 2010 and 2011. The analysis focused on data
      related to demographics, trauma mechanism, clinical course, results of imaging
      scans, concomitant injuries, and outcome. A total of 794 inpatient cases of head
      injury were treated. The leading mechanism of injury was a fall (at home)
      primarily at the age of 1 to 4 years (46.5%), with the majority of the children
      sustaining a mild brain injury (764, 96.2%). Neurosurgery was performed in 21
      (2.64%) cases; average hospital stay was 2.9 days (range: 0-68 days). This study
      is not able to confirm that children are increasingly being brought to the
      hospital by their parents because of new trauma mechanisms or parents'
      uncertainty, nor can we confirm that the number of nonaccidental injuries is
      rising. 

PMID- 25370861
TI  - Increased BDNF protein expression after ischemic or PKC epsilon preconditioning
      promotes electrophysiologic changes that lead to neuroprotection.
AB  - Ischemic preconditioning (IPC) via protein kinase C epsilon (PKCE) activation
      induces neuroprotection against lethal ischemia. Brain-derived neurotrophic
      factor (BDNF) is a pro-survival signaling molecule that modulates synaptic
      plasticity and neurogenesis. Interestingly, BDNF mRNA expression increases after
      IPC. In this study, we investigated whether IPC or pharmacological
      preconditioning (PKCE activation) promoted BDNF-induced neuroprotection, if
      neuroprotection by IPC or PKCE activation altered neuronal excitability, and
      whether these changes were BDNF-mediated. We used both in vitro (hippocampal
      organotypic cultures and cortical neuronal-glial cocultures) and in vivo (acute
      hippocampal slices 48 hours after preconditioning) models of IPC or PKCE
      activation. BDNF protein expression increased 24 to 48 hours after
      preconditioning, where inhibition of the BDNF Trk receptors abolished
      neuroprotection against oxygen and glucose deprivation (OGD) in vitro. In
      addition, there was a significant decrease in neuronal firing frequency and
      increase in threshold potential 48 hours after preconditioning in vivo, where
      this threshold modulation was dependent on BDNF activation of Trk receptors in
      excitatory cortical neurons. In addition, 48 hours after PKCE activation in vivo,
      the onset of anoxic depolarization during OGD was significantly delayed in
      hippocampal slices. Overall, these results suggest that after IPC or PKCE
      activation, there are BDNF-dependent electrophysiologic modifications that lead
      to neuroprotection. 

PMID- 25370863
TI  - LOCFAS-Assessed Evolution of Cognitive and Behavioral Functioning in a Sample of
      Pediatric Patients With Severe Acquired Brain Injury in the Postacute Phase.
AB  - We studied 86 patients with severe acquired brain injuries of different etiology,
      aged 0 to 18 years, in a condition of vegetative state or minimally conscious
      state. During neurorehabilitation, we administered the Level of Cognitive
      Functioning Assessment Scale every 2 weeks in order to describe and compare the
      progressive improvement in their cognitive-behavioral functioning and
      responsiveness in different etiologies. Patients with traumatic brain injury
      showed more favorable clinical outcomes. The higher the level of functioning at
      the first evaluation, the better the outcome, and the higher the Glasgow Coma
      Scale score, the higher the Level of Cognitive Functioning Assessment Scale level
      reached at the end of hospitalization. Patients with an apparently stable
      clinical picture, too, showed a change in their ability to interact with the
      environment. This study underlines the importance of an individualized and early
      cognitive-behavioral intervention protocol that can reveal minimal and
      fluctuating responses. 

PMID- 25370864
TI  - Assessment of gene promoter G-quadruplex binding and modulation by a naphthalene
      diimide derivative in tumor cells.
AB  - Naphthalene diimide (NDI) derivatives have shown high affinity for telomeric
      guanine (G)-quadruplexes and good antiproliferative activity in different human
      tumor experimental models. A trisubstituted compound (H-NDI-NMe2) has been
      reported to stabilize the telomeric G-quadruplex and to cause telomere
      dysfunction and downregulation of telomerase expression. We further investigated
      its mechanism of action by analyzing the capability of the molecule to interfere
      with the expression levels of oncogenes, such as MYC, telome-rase reverse
      transcriptase (TERT), KIT and BCL2, known to bear G-quadruplex-forming sequences
      within their promoters, in human tumor cell lines of different histological
      origin. Exposure to H-NDI-NMe2 resulted in a cell type-dependent perturbation of
      the expression levels of the four selected genes. Biophysical and molecular
      analyses revealed that H-NDI-NMe2 bound with high affinity and effectively
      stabilized mainly MYC and BCL2, which share long sequences and the possibility of
      multiple G-quadruplex folding. The mRNA levels of both genes, but not protein
      amounts were affected by NDI treatment. Global gene expression analysis showed
      modulation of genes implicated in telomere function and mechanisms of cancer;
      however, G-quadruplex-mediated regulation of gene expression by H-NDI-NMe2 was
      largely dependent on the cell context. These data indicate that a deeper
      knowledge on the molecular mechanisms and biological effects of G-quadruplex
      structures is still needed to help developing new effective anticancer agents. 

PMID- 25370865
TI  - Rational design of heterodimeric protein using domain swapping for myoglobin.
AB  - Protein design is a useful method to create novel artificial proteins. A rational
      approach to design a heterodimeric protein using domain swapping for horse
      myoglobin (Mb) was developed. As confirmed by X-ray crystallographic analysis, a
      heterodimeric Mb with two different active sites was produced efficiently from
      two surface mutants of Mb, in which the charges of two amino acids involved in
      the dimer salt bridges were reversed in each mutant individually, with the active
      site of one mutant modified. This study shows that the method of constructing
      heterodimeric Mb with domain swapping is useful for designing artificial
      multiheme proteins. 

PMID- 25370866
TI  - Early onset of fetal hydrops associated with the alpha-thalassemia - -(THAI)
      deletion.
AB  - alpha-Thalassemia (alpha-thal) is common in southern China. Homozygosity for the 
      -(SEA) (Southeast Asian) alpha-globin gene deletion is the most common cause of
      the Hb Bart's (gamma4) disease. Occasionally, other alpha(0)-thal deletions can
      also be found. In this study, we report a case with an atypical form of Hb Bart's
      disease. The fetus was a compound heterozygote for the - -(SEA) and - -(THAI)
      deletions and presented different clinical features from that of traditional Hb
      Bart's disease with the - -(SEA) deletion in the homozygous state. The early
      onset of fetal hydrops is attributed to the decreased formation of embryonic Hb
      Portland (zeta2gamma2), which is proposed as a candidate for reactivation in
      cases of severe alpha-thal. Our finding may have potentially important
      implications for clinical decisions in a program using ultrasonography to
      identify signs of homozygous alpha(0)-thal.

PMID- 25370867
TI  - Molecular characterization of a beta-thalassemia intermedia patient presenting
      inferior vena cava thrombosis: interaction of the beta-globin erythroid Kruppel
      like factor binding site mutation with Hb E and alpha(+)-thalassemia.
AB  - The molecular basis and hematological phenotype of adult Thai beta-thalassemia
      intermedia (beta-TI) patients encountered with inferior vena cava (IVC)
      thrombosis were investigated. Hematological and molecular analysis revealed a
      trait previously not described. The disease was caused by interaction of the
      beta(+)-thalassemia (beta(+)-thal) gene with the -90 (C > T) (HBB: c.-140C > T)
      transition within the erythroid Kruppel-like factor (EKLF) binding site of the
      beta-globin gene promoter with Hb E (HBB: c.79G > A) and alpha(+)-thalassemia
      (alpha(+)-thal). Hematological data of the patient were compared with those of
      heterozygous forms of these defects found in his family members and different
      genotype-phenotype interactions are illustrated. Globin gene haplotype analysis
      indicates an independent origin of this Thai beta(+)-thal gene. Accurate
      diagnoses as well as knowledge of genotype-phenotype relationships were required
      for providing appropriate management of such cases.

PMID- 25370868
TI  - An Alu element-mediated 28.5 kb alpha-thalassemia deletion found in a Chinese
      family.
AB  - Over 95.0% of the alpha-thalassemia (alpha-thal) cases in southern China are
      caused by large deletions involving the alpha-globin gene. Here, we describe the
      molecular characterization of a novel 28.5 kb deletion that eliminated one of the
      duplicated alpha-globin genes in a Chinese family. The deletion breakpoint
      fragment involved Alu repeat sequences, suggesting a homologous recombination
      event. Phenotypic analysis on the heterozygous carrier of this deletion revealed
      that it leads to a very mild phenotype. Because of a 25.0% risk of Hb H (beta4)
      disease in the offspring when in combination with another alpha(0)-thal allele,
      we should not ignore screening the deletion in prenatal diagnosis in order to
      decrease reproductive risk.

PMID- 25370869
TI  - Molecular spectrum of alpha-globin gene defects in the Omani population.
AB  - We describe the molecular characterization of alpha-globin gene defects in a
      cohort of 634 Omani patients. A total of 21 different alpha gene mutations were
      found in 484 subjects. Overall, we identified three different large deletions,
      three small deletions, 11 point mutations [two on the alpha2 polyadenylation
      signal (polyA) (HBA2: c.*94A>G), and nine alpha chain variants], three
      alphaalphaalpha(anti 3.7) triplication, a 21 nucleotide (nt) duplication on the
      alpha1 gene and two novel (presumed) polymorphisms on the alpha 3.7 kb hybrid
      gene, namely -5 (C>T) and +46 (C>A). Of these defects, 15 have not been
      previously reported in the Omani population. This large heterogeneity of alpha
      thalassemia (alpha-thal) observed in the Omani population could be expected in
      neighboring Arab countries. The high frequency of alpha-thal, solely or in
      association with beta-globin gene defects, emphasize the necessity of adding
      alpha-thal testing to pre marital programs for accurate genetic counseling.

PMID- 25370870
TI  - Recurrent pregnancy loss is associated with increased red cell distribution width
      and platelet distribution width.
AB  - AIM: The present study aims to evaluate how components of complete blood count
      are altered in women with a history of recurrent pregnancy loss. MATERIAL AND
      METHODS: This was a retrospective evaluation of 60 women who had a history of
      recurrent pregnancy loss, 60 healthy women who had a first trimester pregnancy
      and 60 healthy parous women. RESULTS: When compared with pregnant women and
      healthy controls, the women with a history of recurrent pregnancy loss had
      significantly higher red cell distribution width (RDW) and platelet distribution
      width (PDW) (P = 0.001 for both). Thrombophilia was detected in 31.7% of the
      women who had a history of recurrent pregnancy loss (19 out of 60). When compared
      to the women without thrombophilia, the women with thrombophilia had
      significantly lower body mass index (P = 0.034) but significantly higher RDW, PDW
      and plateletcrit (respectively, P = 0.043, P = 0.001 and P = 0.002). There were
      significant and positive correlations between RDW and PDW (r = 0.615, P = 0.001),
      RDW and plateletcrit (r = 0.343, P = 0.007) and PDW and plateletcrit (r = 0.340,
      P = 0.008) in women with a history of recurrent pregnancy loss. CONCLUSION: An
      elevation in PDW and RDW values was found to be associated with recurrent
      pregnancy loss.

PMID- 25370871
TI  - Pseudocarcinomatous hyperplasia mimicking squamous cell carcinoma in a case of
      CD56-positive cytotoxic T-cell lymphoma.
AB  - We present the case of an 84-year-old patient with a cutaneous CD56 positive
      cytotoxic T-cell lymphoma associated with substantial pseudocarcinomatous
      hyperplasia mimicking squamous cell carcinoma (SCC). The patient presented with a
      7-month history of several progressive, ulcerated plaques on his right forearm.
      An initial biopsy showed changes consistent with a diagnosis of SCC for which the
      patient underwent surgical treatment. Several months later, the patient developed
      recurrent ulcerated plaques on the right forearm of which several biopsies were
      performed. The biopsies repeatedly showed marked pseudocarcinomatous hyperplasia
      resembling SCC. Deeper punch biopsies, however, showed a dense superficial and
      deep infiltrate of markedly atypical lymphocytes. Immunohistochemical analysis
      revealed strong positive staining for CD3, CD8, CD56 with negative stains for
      CD30 and Epstein-Barr virus-encoded small non-polyadenylated RNAs (EBER).
      Staining for beta F1 and gamma-delta T-cell receptor (gammadelta TCR) were both
      negative. This constellation was most consistent with a diagnosis of cutaneous
      peripheral T-cell lymphoma, unspecified in association with marked
      pseudocarcinomatous hyperplasia. Our case adds cutaneous peripheral T-cell
      lymphoma, unspecified to the list of conditions associated with
      pseudocarcinomatous hyperplasia (PCH) and illustrates once again the potential
      pitfalls of distinguishing marked pseudocarcinomatous hyperplasia from SCC. 

PMID- 25370872
TI  - Direct 2D measurement of time-averaged forces and pressure amplitudes in
      acoustophoretic devices using optical trapping.
AB  - Ultrasonic standing waves are increasingly applied in the manipulation and
      sorting of micrometer-sized particles in microfluidic cells. To optimize the
      performance of such devices, it is essential to know the exact forces that the
      particles experience in the acoustic wave. Although much progress has been made
      via analytical and numerical modeling, the reliability of these methods relies
      strongly on the assumptions used, e.g. the boundary conditions. Here, we have
      combined an acoustic flow cell with an optical laser trap to directly measure the
      force on a single spherical particle in two dimensions. While performing
      ultrasonic frequency scans, we measured the time-averaged forces on single
      particles that were moved with the laser trap through the microfluidic cell. The
      cell including piezoelectric transducers was modeled with finite element methods.
      We found that the experimentally obtained forces and the derived pressure fields
      confirm the predictions from theory and modeling. This novel approach can now be
      readily expanded to other particle, chamber, and fluid regimes and opens up the
      possibility of studying the effects of the presence of boundaries, acoustic
      streaming, and non-linear fluids. 

PMID- 25370873
TI  - Computer navigation and robotics in orthopedic surgery.

PMID- 25370874
TI  - Computer-assisted and robotic surgery in orthopedics: where we are in 2014.
AB  - Successful outcomes after orthopedic surgical procedures are believed to be
      highly dependent on reproducible anatomic accuracy. Immediate intraoperative
      feedback helps surgeons to achieve this accuracy as has been demonstrated with
      the use of fluoroscopy. Non-image-based computer navigation has been used in
      joint arthroplasty, anterior cruciate ligament reconstruction, high tibial
      osteotomy, and cartilage procedures along with applications in hip and shoulder
      arthroscopy. Most short-term studies have demonstrated superior accuracy when
      compared with conventional techniques; however, very few studies have shown
      better clinical outcomes. Robotic-assisted surgery has been most popular in total
      and unicompartmental arthroplasty, which again has greater accuracy but similar
      clinical outcomes when compared with conventional techniques. Economic analyses
      indicate that these high-cost technologies may only be cost-effective in high
      volume centers. Other studies have shown that computer navigation improves the
      accuracy of lower volume surgeons to a greater degree than higher volume surgeons
      allowing the former to have results similar to the latter. 

PMID- 25370875
TI  - Computer-assisted anterior cruciate ligament (ACL) reconstruction: the US
      perspective.
AB  - Computer-assisted anterior cruciate ligament (ACL) reconstruction in the United
      States has been used to help improve clinical outcomes and investigate tunnel
      placement and kinematic activity. Computer-assisted techniques were developed to
      improve accuracy of tunnel placement, because of concerns about the accuracy of
      manual tunnel placement causing revisions. Several authors have demonstrated
      improved tunnel location with computer assistance, although others have
      demonstrated little or no difference. More recently, American investigators have
      used computer assistance to evaluate the position and biomechanical behavior and
      kinematics of theoretical tunnel placement and also to assess in vitro and in
      vivo knee stability following ligament reconstruction. Computer assistance of
      anterior ligament reconstruction has demonstrated its value as a research and
      clinical tool in the United States. 

PMID- 25370876
TI  - A novel computer navigation system for retrograde drilling of osteochondral
      lesions.
AB  - Osteochondritis dissecans (OCD) represents an important clinical entity in
      orthopedic sports medicine. Once surgical intervention is required, retrograde
      drilling for OCD lesions remains technically challenging. A novel electromagnetic
      navigation system was developed to be a radiation-free navigation tool providing
      spatiotemporal real-time information to the surgeon without the need for a
      stationary patient tracker and without relevant setup and calibration times. The
      novel system was tested for arthroscopically assisted retrograde drilling of
      cadaveric OCD lesions of the knee and talus and compared with the gold standard
      fluoroscopy-guided retrograde drilling procedure in a controlled laboratory study
      setup. The novel method considerably improves on the standard operating procedure
      in terms of safety, operation time, and radiation exposure and will be available
      for further surgical indications. 

PMID- 25370877
TI  - Robotic-assisted unicompartmental knee arthroplasty.
AB  - In recent years, development of computer graphics and haptic feedback technology
      enabled the use of virtual reality. Virtual reality provides the opportunity to
      combine 3D visual imagery with interactivity, visual, and tactile realism.
      Robotic-assisted orthopedic surgery is defined as the use of computers and
      robotic technology to assist the orthopedist in providing musculoskeletal care,
      in which machine has the capability of precision and accuracy. Robotic-assisted
      orthopedic surgery is used in simulating diagnosis, preoperative and
      intraoperative planning, and actual surgery. One of the main areas for computer
      assisted surgical applications is unicompartmental or bicompartmental knee
      arthroplasty, in which the clinical efficacy is improved by providing enhanced
      component positioning with dynamic ligament balancing. 

PMID- 25370878
TI  - Lateral robotic unicompartmental knee arthroplasty.
AB  - Robotic-assisted unicompartmental knee arthroplasty (UKA) is accurate and
      repeatable. Lateral UKA is still considered a challenge, as the lateral side of
      the knee has different anatomy and kinematics compared with the medial side. The
      lateral compartment of the knee is less constrained than the medial compartment
      and is therefore less tolerant for mobile-bearing implants and ACL deficiency.
      However, the long-term outcomes of lateral UKA are scarce. Moreover, the impact
      of patellofemoral joint degeneration on the outcome of lateral UKA is unknown. We
      report our preliminary results with fixed bearing robotic-assisted lateral UKA,
      which are encouraging in the short term. 

PMID- 25370881
TI  - Pros, cons, and future possibilities for use of computer navigation in hip
      arthroscopy.
AB  - The recent integration of computer-assisted surgery as a resource for
      preoperative planning and intraoperative assistance in hip arthroscopy has paved
      the way for more precise surgical planning and the potential for improved
      operative results. The aims of computer-assisted surgery are to better define the
      pathoanatomy underlying patient symptomatology in an effort to refine surgical
      techniques, decrease human error, and ultimately improve clinical outcomes.
      Multiple studies have been published describing various technologies. The
      majority of these systems create 3D dynamized computer models from 2D CT scans to
      allow for precise preoperative planning, and some offer real-time intraoperative
      capabilities. Although these technologies have shown potential for increasing
      surgical precision in treating femoroacetabular impingement, they are not without
      limitations, including an inability to factor in soft-tissue structures and an
      incompatibility with dysplastic and arthritic hips. Future studies must be
      conducted to determine whether these systems result in improved clinical
      outcomes. 

PMID- 25370882
TI  - Computer navigation and patient-specific instrumentation in shoulder
      arthroplasty.
AB  - Longevity of total anatomic and reversed shoulder arthroplasty largely depends on
      accurate correction of glenoid deformity and correct positioning and fixation of
      the glenoid component. However, the morphology of the scapula is inconsistent,
      varying degrees of osteoarthritis cause numerous anatomic changes, and standard 2
      dimensional imaging and standard surgical instrumentation are imprecise for
      preoperative planning and execution of glenoid reconstruction. Recently, various
      authors have shown that preoperative 3-dimensional surgical planning and computer
      navigation technology may increase the accuracy and repeatability of the
      implantation of the glenoid component, especially for the position and
      orientation of the glenosphere and screws in reversed arthroplasty. These novel
      techniques may allow the surgeon to better define the preoperative deformity,
      select the optimal implant position, and then accurately execute the plan at the
      time of surgery. Future studies are needed to determine the long-term effect on
      functional outcome and cost-effectiveness of computer-assisted technology in
      shoulder arthroplasty. 

PMID- 25370884
TI  - Greenhouse seedlings of Alnus showed low host intrageneric specificity and a
      strong preference for some Tomentella ectomycorrhizal associates.
AB  - Ectomycorrhizal (ECM) fungal associates of Alnus are relatively few in comparison
      with those associated with other tree hosts. The composition of ECM assemblages
      associated with Alnus seems to change very little across the Northern Hemisphere.
      However, Alnus-associated ECM assemblages from the Western United States, Mexico,
      and Argentina tend to differ from those in eastern North America and Europe,
      presumably due to their different biogeographic histories. Alnus glutinosa is a
      northern European species subjected to diverse environmental conditions. To
      address intrageneric host preference within two distantly related Alnus species
      (Alnus acuminata and A. glutinosa), we tested the ECM colonization on seedlings
      of both species inoculated with natural soil from A. acuminata forests. Two
      tomentelloid ECM fungi from A. acuminata natural soils were determined from the
      anatomotyping and molecular analysis. Both species colonized A. glutinosa
      seedlings and presented similar relative abundances. Additional soil sequence
      data from A. acuminata sites suggest that a variety of tomentelloid taxa occur,
      including several unidentified Tomentella lineages. Maximum-likelihood and
      Bayesian inference analyses based on internal transcribed spacer (ITS) sequences
      from various locations do not reflect associations of taxa based on their
      biogeographic origin, and clades are in general constituted by sequences from
      diverse regions, including South America, Mexico, USA, and Europe. Results
      illustrate the probable role of specific tomentelloid fungi in the early
      colonization of seedlings in A. acuminata forests as well as their importance in
      the structure of the ECM propagule community at the sites. 

PMID- 25370883
TI  - A social-ecological analysis of community perceptions of dengue fever and Aedes
      aegypti in Machala, Ecuador.
AB  - BACKGROUND: The growing burden of dengue fever and the lack of a vaccine or
      specific medical treatment have increased the urgency of the public health sector
      to identify alternative management strategies. A prevailing trend in Latin
      America has been a shift towards decentralized vector control programs with
      integrated management strategies, requiring significant intersectoral
      coordination, community engagement, and knowledge of the local social-ecological
      system (SES). Community perceptions and responses are a critical component of
      this system, since perceptions shape actions, and thus govern behavioral
      responses and acceptance of shifts in policy and management. METHODS: We
      investigated perceptions, misconceptions, and local SES risk factors for dengue
      in high risk communities located at the urban periphery and center in Machala,
      Ecuador. We facilitated twelve focus group discussions with community members
      using semi-structured question guides and causal diagrams. Focus groups were
      recorded, transcribed, and coded to identify emergent themes using qualitative
      methods for theme analysis. To estimate the relative importance of the themes in
      each study area, we tabulated the number of focus groups in which each theme was
      present. Household surveys (n = 79) were conducted to further explore these
      themes, and we compared survey responses from the two areas using descriptive
      statistics. RESULTS: We identified thirty biophysical, political-institutional,
      and community-household risk factors for dengue. People at the periphery
      identified a greater number of risk factors. Dengue control required considerable
      investment of time and resources, which presented a greater challenge for women
      and people at the periphery. Common misperceptions included confusion with other
      febrile diseases, lack of knowledge of transmission mechanisms, and
      misconceptions about mosquito behavior. People perceived that dengue control
      programs had been limited by the lack of inter-institutional coordination and
      lack of social cohesion. CONCLUSIONS: There is a need for local, policy-relevant
      research that can be translated to strengthen the design, implementation, and
      evaluation of new dengue management strategies. This study contributes to a
      growing body of research in this area. Based on these findings, we identify key
      policy and management recommendations that will inform the ongoing transition to
      a decentralized dengue control program in Ecuador and other dengue endemic
      countries.

PMID- 25370885
TI  - Parent material and vegetation influence soil microbial community structure
      following 30-years of rock weathering and pedogenesis.
AB  - The process of pedogenesis and the development of biological communities during
      primary succession begin on recently exposed mineral surfaces. Following 30 years
      of surface exposure of reclaimed surface mining sites (Appalachian Mountains,
      USA), it was hypothesized that microbial communities would differ between
      sandstone and siltstone parent materials and to a lesser extent between
      vegetation types. Microbial community composition was examined by targeting
      bacterial and archaeal (16S ribosomal RNA (rRNA)) and fungal (internal
      transcribed spacer (ITS)) genes and analyzed using Illumina sequencing. Microbial
      community composition significantly differed between parent materials and between
      plots established with tall fescue grass or pitch x loblolly pine vegetation
      types, suggesting that both factors are important in shaping community assembly
      during early pedogenesis. At the phylum level, Acidobacteria and Proteobacteria
      differed in relative abundance between sandstone and siltstone. The amount of the
      heavy fraction carbon (C) was significantly different between sandstone (2.0 mg
      g(-1)) and siltstone (5.2 mg g(-1)) and correlated with microbial community
      composition. Soil nitrogen (N) cycling was examined by determining gene copy
      numbers of ureC, archaeal amoA, and bacterial amoA. Gene quantities tended to be
      higher in siltstone compared to sandstone but did not differ by vegetation type.
      This was consistent with differences in extractable ammonium (NH4 (+))
      concentrations between sandstone and siltstone (16.4 vs 8.5 MUg NH4 (+)-N g(-1)
      soil), suggesting that nitrification rates may be higher in siltstone. Parent
      material and early vegetation are important determinants of early microbial
      community assembly and could be drivers for the trajectory of ecosystem
      development over longer time scales.

PMID- 25370886
TI  - Generalized soil Thaumarchaeota community in weathering rock and saprolite.
AB  - Relatively little is known of the archaeal communities associated with endolithic
      environments, compared to other microbial groups such as bacteria and fungi.
      Analyzing the pyrosequenced archaeal 16S ribosomal RNA (rRNA) gene V1-V3 region,
      we investigated the archaeal community associated with aboveground-exfoliated
      weathering layers of a granite gneiss, and of the saprolite derived from this
      rock at 1 m depth below the soil surface, in a forested hilly area south of
      Seoul, South Korea. In both these sites, an archaeal community dominated by the
      phylum Thaumarchaeota was identified. The archaeal community in all cases closely
      resembled that of the surface layer of acidic soils in temperate climates of
      Korea. It appears that there is no clear distinction in archaeal community
      composition between a soil and a rock and a saprolite despite a tremendous
      difference in the concentration of total nitrogen and organic carbon. Of the
      chemical properties we measured, pH was the best predictor of the archaeal
      community composition and relative abundance of thaumarchaeal subphyla. These
      findings reinforce the view that soil archaea are mostly generalists, whose
      ecology is not closely dependent on nitrogen concentration or soil organic matter
      status, the presence of living roots, or the abundant presence of any other
      biota.

PMID- 25370887
TI  - Effects of Elevated Atmospheric CO2 on Microbial Community Structure at the Plant
      Soil Interface of Young Beech Trees (Fagus sylvatica L.) Grown at Two Sites with
      Contrasting Climatic Conditions.
AB  - Soil microbial community responses to elevated atmospheric CO2 concentrations
      (eCO2) occur mainly indirectly via CO2-induced plant growth stimulation leading
      to quantitative as well as qualitative changes in rhizodeposition and plant
      litter. In order to gain insight into short-term, site-specific effects of eCO2
      on the microbial community structure at the plant-soil interface, young beech
      trees (Fagus sylvatica L.) from two opposing mountainous slopes with contrasting
      climatic conditions were incubated under ambient (360 ppm) CO2 concentrations in
      a greenhouse. One week before harvest, half of the trees were incubated for 2
      days under eCO2 (1,100 ppm) conditions. Shifts in the microbial community
      structure in the adhering soil as well as in the root rhizosphere complex (RRC)
      were investigated via TRFLP and 454 pyrosequencing based on 16S ribosomal RNA
      (rRNA) genes. Multivariate analysis of the community profiles showed clear
      changes of microbial community structure between plants grown under ambient and
      elevated CO2 mainly in RRC. Both TRFLP and 454 pyrosequencing showed a
      significant decrease in the microbial diversity and evenness as a response of CO2
      enrichment. While Alphaproteobacteria dominated by Rhizobiales decreased at eCO2,
      Betaproteobacteria, mainly Burkholderiales, remained unaffected. In contrast,
      Gammaproteobacteria and Deltaproteobacteria, predominated by Pseudomonadales and
      Myxococcales, respectively, increased at eCO2. Members of the order
      Actinomycetales increased, whereas within the phylum Acidobacteria subgroup Gp1
      decreased, and the subgroups Gp4 and Gp6 increased under atmospheric CO2
      enrichment. Moreover, Planctomycetes and Firmicutes, mainly members of Bacilli,
      increased under eCO2. Overall, the effect intensity of eCO2 on soil microbial
      communities was dependent on the distance to the roots. This effect was
      consistent for all trees under investigation; a site-specific effect of eCO2 in
      response to the origin of the trees was not observed. 

PMID- 25370888
TI  - Adaptation of an evidence-based clinical practice guideline in cancer pain
      management by medical oncologists: a case vignette study.
AB  - PURPOSE: Pain is a major problem in all cancer stages. Cancer pain guidelines are
      developed to improve management of pain. It is unclear whether these
      recommendations are applied in daily practice. Therefore, the objective of this
      study was to assess medical oncologists' adherence to an evidence-based clinical
      practice guideline in cancer pain management and their confidence in treatment
      choices. METHODS: A cross-sectional case vignette survey describing a patient
      with intractable pancreatic cancer and pain was sent to all 268 medical
      oncologists registered at the Netherlands Association of Internal Medicine.
      Descriptive statistics were conducted. RESULTS: Sixty-three of 268 medical
      oncologists (24 %) completed the survey. Adherence to the different
      recommendations of the guideline ranged from 18 to 100 %. Confidence for
      treatment choice ranged from 5.6 to 9.5 on a Numeric Rating Scale (0-10). Most of
      the responding oncologists (94 %) adhered to prescribing paracetamol as first
      line pain treatment, and all prescribed a laxative in combination with opioids to
      prevent constipation. However, only 24 % of the respondents adhered to the
      guideline when first-line treatment had insufficient effect. Additionally, only
      35 % adhered to the recommendation for insomnia treatment providing psychosocial
      support or using a multidimensional pain questionnaire besides pharmacological
      treatment. Finally, only 18 % adhered to the recommendation to perform a
      multidimensional pain assessment when disease worsens and pain increases.
      CONCLUSIONS: The recommendations of the guideline have been partly adopted in
      cancer pain practice by medical oncologists. Particularly, pain assessment is not
      applied in the recommended manner. Therefore, implementation strategies should
      focus on adequate pain assessment in patients with cancer.

PMID- 25370889
TI  - A phase 3 trial of armodafinil for the treatment of cancer-related fatigue for
      patients with multiple myeloma.
AB  - PURPOSE: Fatigue is a common problem among multiple myeloma (MM) patients.
      Armodafinil is a drug known to promote wakefulness, which is related to
      modafinil, a compound that improves fatigue in some cancer patients treated with
      chemotherapeutic agents. We investigated whether armodafinil could reduce cancer
      related fatigue in MM patients. METHODS: This double-blind, placebo-controlled
      phase 3 trial evaluated the efficacy of armodafinil in MM patients with evidence
      of moderate fatigue. Patients were randomized to one of two arms: treatment-only,
      with armodafinil given at 150 mg/daily for 56 days, or placebo-first, with
      placebo given on days 1-28, followed by armodafinil administered at 150 mg daily
      on days 29-56. Fatigue was measured on days 1 (pre-dose: baseline), 15, 28, 43,
      and 56 using seven separate assessments, including four patient-reported outcomes
      of fatigue and related quality of life measures, as well as three objective
      measures of cognitive function. RESULTS: Overall toxicities were similar between
      treatment groups. No significant differences were observed between the placebo
      first and the treatment-only arms after 28 days. Treatment with armodafinil for
      28 additional days did not produce responses. Both placebo-first and treatment
      only patients showed similar significant improvements in three patient-reported
      measures and one objective task at day 28 compared to baseline. Placebo-first
      patients improved on eight additional measures (one patient-reported measure, six
      subscales, and one objective task), suggesting a strong placebo effect in this
      patient population. CONCLUSIONS: Evaluation and treatment of cancer-related
      fatigue continues to be challenging; a clear definition of this symptom and
      better assessment tools are needed.

PMID- 25370890
TI  - Nutri-jelly may improve quality of life and decrease tube feeding demand in head
      and neck cancer patients.
AB  - PURPOSE: Eating difficulty is a critical and common problem in head and neck
      cancer patients undergoing radiotherapy (RT). It leads to poor quality of life
      and extensive tube feeding use. Nutri-jelly, a food gel with semisolid texture,
      water-releasing ability, and ready-to-eat by spoon, was recently developed to
      alleviate the trouble. However, its efficacy was unknown. This study investigated
      the potential effect of Nutri-jelly on health-related quality of life (HRQOL) and
      nasogastric tube feeding use. METHODS: A prospective quasi-randomized patients
      preference controlled trial was conducted in 74 head and neck cancer patients.
      Subjects in study and control groups (37 each) had similar baseline HRQOL and
      body mass index and undergone definitive radiotherapy (25-35 RT fractions, 5,000
      7,000 cGy). Only study group received a 200-ml box of Nutri-jelly as daily
      supplement throughout radiotherapy. HRQOL was scored by validated questionnaires.
      The use of tube feeding was collected from medical records. RESULTS: From 11 to
      35 RT fractions, the study group maintained higher overall HRQOL score than that
      of control group (p < 0.0001). Multiple physiologic and psychological aspects of
      HRQOL especially swallowing difficulty and overall eating problems were
      significantly improved in study as compared to control group. Promisingly, the
      percentage of tube feeding use in study group (13.5 %) was dramatically lower
      than control group (48.6 %). CONCLUSIONS: Continuous supplementation of Nutri
      jelly throughout radiotherapy may improve HRQOL and reduce tube feeding demand in
      head and neck cancer patients who preferred to take them. Nutri-jelly could be an
      alternative for head and neck cancer patients who have eating difficulty during
      radiotherapy.

PMID- 25370891
TI  - Sleep status of cervical cancer patients and predictors of poor sleep quality
      during adjuvant therapy.
AB  - PURPOSE: This study was designed to detect the prevalence of poor sleep quality
      in cervical cancer patients before and after adjuvant therapy, determine whether
      the prevalence of poor sleep quality in cervical cancer patients is higher than
      that in the general population, and analyze the factors associated with poor
      sleep quality. METHODS: A total of 76 stages I and II cervical cancer patients
      and 116 female residents completed the Pittsburgh Sleep Quality Index (PSQI).
      Patient Neurotoxicity Questionnaire (PNQ), Distress Thermometer (DT),
      Multidimensional Fatigue Inventory, and Hospital Anxiety and Depression Scale
      were used to measure the patients' chemotherapy-induced peripheral neurotoxicity
      (CIPN), psychological distress, fatigue, anxiety, and depression. Data on social
      support and exercise were collected by the questionnaire. Logistic regression was
      used to identify the factors associated with poor sleep quality. RESULTS:
      Prevalence rates of poor sleep quality were 27.59 % for female residents, 52.63 %
      for patients before adjuvant therapy, and 64.50 % for patients after adjuvant
      therapy. The distributions of the PSQI scores of the patients before (Z = 3.814,
      P < 0.001) and after (Z = 5.957, P < 0.001) adjuvant therapy were different from
      those of the residents. The difference in the PSQI scores before and after
      adjuvant therapy among cervical cancer patients was significant (P = 0.007). The
      factors associated with poor sleep quality were high DT score (P = 0.045),
      depression (P = 0.028), anxiety (P = 0.027), high PNQ grade (P = 0.016), and
      chemotherapy + radiotherapy treatment (P = 0.017). Exercise was a protective
      factor for poor sleep quality (P =0.019). CONCLUSION: The prevalence of poor
      sleep quality in stages I and II cervical cancer patients was approximately twice
      than that of women in the communities. Cancer treatment considerably affected
      sleep quality. Psychological distress, depression, anxiety, and high grade of
      CIPN during adjuvant therapy were factors associated with poor sleep quality.
      Exercise during adjuvant therapy could reduce the risk of poor sleep quality.

PMID- 25370892
TI  - Mind the gaps: missed opportunities to promote bone health among cancer
      survivors.
AB  - INTRODUCTION: Many cancer treatments have a negative effect on bone health and
      can lead to osteoporosis. Additionally, the risk of osteoporosis during cancer
      survivorship may differ by racial and ethnic group. Overall, cancer survivors may
      be poorly informed about the risk of bone loss due to treatment. EXERCISE
      PRESCRIPTION: Exercise can be prescribed to improve bone health and reduce risk
      of fracture. Women participating in the Improving Physical Activity After Cancer
      Treatment pilot study (IMPAACT) experienced significant improvements in bone
      health. The pilot work also suggests that cancer survivors of diverse
      racial/ethnic profiles may not fit the normal risk profile for osteoporosis and
      could be overlooked during screening. IN SUMMARY: The lack of awareness of poor
      bone health in cancer survivors needs to be addressed, especially for those who
      do not fit the normal osteoporosis risk profile. Exercise is a safe and effective
      part of a cancer survivorship plan and is useful in promoting bone health.

PMID- 25370894
TI  - Obstacles to adherence to azacitidine administration schedule in outpatient
      myelodysplastic syndrome and related disorders.

PMID- 25370893
TI  - NRS-2002 for pre-treatment nutritional risk screening and nutritional status
      assessment in head and neck cancer patients.
AB  - BACKGROUND: The aim of this study was to assess the value of nutritional risk
      screening-2002 (NRS-2002) as a nutritional risk screening and status assessment
      method and to compare it with nutritional status assessed by subjective and
      objective methods in the screening of head and neck cancer patients. METHODS:
      Sixty-five consecutive patients (50 male), with a median age of 61 years (range,
      33-77), with head and neck squamous cell carcinoma (HNSCC) were enrolled prior to
      cancer therapy. Nutritional status was assessed by NRS-2002, patient-generated
      subjective global assessment (PG-SGA), handgrip strength (HGS) and mid-arm muscle
      area (MAMA). RESULTS: Twenty-eight percent of patients were at nutritional risk
      based on NRS-2002, and 34 % were malnourished according to PG-SGA, while 43 % had
      low HGS. NRS-2002 cut-off score of >=3 compared with the nutritional status
      according to PG-SGA showed 77 % specificity and 98 % sensitivity (K = 0.78). NRS
      2002 was able to predict malnutrition (PG-SGA BC) both in men (p < 0.001) and in
      women (p < 0.05). NRS-2002 identified correctly patients with malnutrition with a
      score of >=3 (p < 0.001) and risk patients with a score of >=2 (p < 0.001).
      CONCLUSIONS: These results suggest that NRS-2002 seems to be a reliable indicator
      of malnutrition, while NRS-2002 with the cut-off score of >=2 seems to be more
      reliable for nutrition screening in head and neck cancer patients prior to
      oncological treatment.

PMID- 25370895
TI  - Emergence and dissemination of multi-resistant Gram negative Enterobacteriaceae:
      lessons to be learnt from local and national surveillance programs in Belgium.
AB  - Infections caused by multi drug resistant bacteria (MDRB) constitutes an
      international health care problem. Since the year 2000, a longitudinal
      surveillance programme (LSP) and two multicentric surveys (100 hospitals, 826
      isolates) were performed to monitor the emergence of MDRB in Belgium. The
      implementation of a LSP detected the emergence and spread of new types of ESBLs
      (CTX-M), mostly among community associated E. coli in the setting of a university
      hospital several years before the large spread and recognition in Belgium of a
      pathogenic E. coli CTX-M-15 (B2-O25:H4-ST131) pandemic clone (found in extra
      intestinal virulent strains). This finding supports the progressive increase in
      Belgium of systemic infections including UTI caused by MDRB with limited
      therapeutical options. The real burden of the problem remains however, difficult
      to estimate in the absence of any surveillance network in Belgium to monitor the
      epidemiology of antimicrobial resistance in the community. The current Belgian
      national recommendations for the detection, surveillance, prevention and control
      of epidemics by ESBL-producing organisms and possibly other MDRBs (eg:
      Carbapenemase producing Enterobacteriaceae [CPE]) must be updated taking into
      accounts these new elements. A global coordinated network for antimicrobial
      surveillance resistance gathering experts (e.g: public health epidemiologists,
      representative of the national reference centres of antimicrobial resistance,
      field experts in infection control, infectious disease specialists, other
      clinicians and general practitioners) must be urgently implemented, including the
      longitudinal analysis of resistance in different ecosystems (human, animal, water
      and food). 

PMID- 25370896
TI  - Identification of miR-125a-5p as a tumor suppressor of renal cell carcinoma,
      regulating cellular proliferation, migration and apoptosis.
AB  - miR-125a-5p has been previously described as a tumor suppressor in numerous
      malignancies, however the expression and function of miR-125a-5p in renal cell
      carcinoma (RCC) remains to be elucidated. In the present study, to explore the
      potential role of miR-125a-5p in RCC, quantitative polymerase chain reaction was
      used to determine the expression levels of miR-125a-5p in renal cancer tissues.
      The influence of miR-125a-5p on cell proliferation, migration and apoptosis was
      also determined, using an MTT assay, a wound scratch assay and flow cytometry,
      respectively. The expression of miR-125a-5p was shown to be decreased in RCC and
      the restoration of miR-125a-5p by synthetic mimics was shown to suppress cell
      proliferation and migration, and induce apoptosis. The present results indicate
      that miR-125a-5p may function as a tumor suppressor in RCC. The present study is,
      to the best of our knowledge, the first to demonstrate the downregulation of miR
      125a-5p in RCC, and to show the role it has in affecting cellular proliferation,
      migration and apoptosis. Further research is needed to define the target genes of
      miR-125a-5p and explore the potential of miR-125a-5p as a diagnostic or a
      prognostic biomarker for RCC.

PMID- 25370897
TI  - Orchiectomy and radiotherapy for stage I-II testicular seminoma: a prospective
      evaluation of short-term effects on body image and sexual function.
AB  - INTRODUCTION: Orchiectomy followed by infradiaphragmatic radiotherapy is a common
      treatment for stage I-II testicular seminoma. Long-term effects of orchiectomy
      and radiotherapy for testicular seminomas on body image and sexual function have
      been reported; however, few data are available on short-term effects. Patients
      are usually of reproductive age and sexually active; therefore, short-term
      effects on body image and sexual function should also be studied. AIMS: To
      prospectively evaluate short-term effects of orchiectomy and radiotherapy on body
      image and sexual function in testicular seminoma patients. METHODS:
      Questionnaires on body image and sexual function were prospectively distributed
      to all testicular seminoma patients treated between 1999 and 2013. The
      questionnaire distributed prior to radiotherapy was returned by 161 patients; 133
      (82%) returned the second after 3 months, and 120 (75%) completed the
      questionnaire after 6 months. MAIN OUTCOME MEASURES: Body image and sexual
      function as assessed by a Dutch questionnaire on body image and sexuality after
      radiotherapy and orchiectomy. RESULTS: Median age was 36 years (range 18-70).
      After orchiectomy, 48% expressed fertility concerns, and 61% reported their body
      had changed. Six months after treatment, erectile rigidity was significantly
      decreased compared with prior to radiotherapy (P = 0.016), and 23% reported
      decreased sexual interest, activity, and pleasure. Changes in body image were
      significantly associated with decreased sexual interest, pleasure, and erectile
      function. Even though 45% reported that treatment negatively affected their
      sexual life, the number of sexually active patients remained stable at 91%.
      [Correction added on 12 November 2014, after first online publication: 'prior
      radiotherapy' was corrected to 'prior to radiotherapy'.] CONCLUSIONS: Short-term
      effects of treatment included fertility concerns and changes in body image.
      Reported erectile rigidity was significantly decreased after 6 months, as were
      sexual interest, activity, and pleasure. Disease and treatment had negative
      effects on sexual life, and changes in body image were associated with sexual
      dysfunction. Therefore, body image and sexual functioning should be addressed at
      an early stage in order to offer adequate treatment and counseling.

PMID- 25370898
TI  - The defect of SFRP2 modulates an influx of extracellular calcium in B
      lymphocytes.
AB  - BACKGROUND: In the Wnt pathway, the secreted frizzled-related protein 2 (SFRP2)
      is thought to act as one of the several competitive inhibitors of Wnt. However,
      the precise role of SFRP2 is still poorly understood especially in B lymphocytes.
      Here, we investigated the function of SFRP2, comparing the SFRP2 defective as
      well as normal B lymphocytes in mice. RESULTS: We demonstrated that calcium
      influx from extracellular to intracellular space in splenic B cells was clearly
      affected by the defect of SFRP2. In addition, the phosphorylation of
      phospholipase Cgamma2 was observed to be reduced in SFRP2 defective splenic B
      cells with B cell receptor stimulation. CONCLUSIONS: SFRP2 is suggested to
      modulate the influx from extracellular calcium in the B cell receptor signaling
      pathway.

PMID- 25370900
TI  - A case of probable labetalol induced hyperkalaemia in pre-eclampsia.
AB  - CASE DESCRIPTION: Hyperkalemia can cause altered cardiac electrical conduction
      resulting in death. We describe a case of a 23-year old pregnant patient who
      presented with severe epigastric pain and vomiting. She was severely pre-
      eclamptic and received initial treatment with intravenous labetalol and decision
      was taken to deliver. She quickly became hyperkalaemic (serum potassium level 6.4
      mmol/L) and labetalol was discontinued and intravenous hydralazine commenced.
      Post-surgery, her potassium levels were normal but due to rapidly rising blood
      pressure labetalol was recommenced, resulting in elevated potassium levels.
      Labetolol was discontinued, hydralazine prescribed, and potassium levels
      normalised. The adverse reaction was classified as 'probably' due to labetolol
      using the Naranjo Adverse Drug Reaction scale. CONCLUSION: This is the first
      reported case of labetolol induced hyperkalaemia in pregnancy, with life
      threatening consequences and hence all health professionals should be alert to
      this potential effect.

PMID- 25370899
TI  - Genetic markers for toxicity of adjuvant oxaliplatin and fluoropyrimidines in the
      phase III TOSCA trial in high-risk colon cancer patients.
AB  - We investigated 17 polymorphisms in 11 genes (TS, MTHFR, ERCC1, XRCC1, XRCC3,
      XPD, GSTT1, GSTP1, GSTM1, ABCC1, ABCC2) for their association with the toxicity
      of fluoropyrimidines and oxaliplatin in colorectal cancer patients enrolled in a
      prospective randomized trial of adjuvant chemotherapy. The TOSCA Italian adjuvant
      trial was conducted in high-risk stage II-III colorectal cancer patients treated
      with 6 or 3 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In the
      concomitant ancillary pharmacogenetic study, the primary endpoint was the
      association of polymorphisms with grade 3-4 CTCAE toxicity events (grade 2-4 for
      neurotoxicity). In 517 analyzed patients, grade >= 3 neutropenia and grade >= 2
      neurotoxicity events occurred in 150 (29%) and in 132 patients (24.8%),
      respectively. Diarrhea grade >= 3 events occurred in 34 (6.5%) patients. None of
      the studied polymorphisms showed clinically relevant association with toxicity.
      Hopefully, genome-wide association studies will identify new and more promising
      genetic variants to be tested in future studies. 

PMID- 25370901
TI  - Acute and fatal thrombocytopenic thrombotic purpura after a single dose of
      pemetrexed.
AB  - CASE: Thrombocytopenic thrombotic purpura (TTP), a life-threatening event
      consisting of disseminated vascular thrombosis, has never been described before
      as a possible side effect of the anticancer drug pemetrexed. A 70 years old
      patient affected by a poorly differentiated non small cell lung cancer, subjected
      to his first pemetrexed administration, developed an acute thrombocytopenic
      thrombotic purpura, fatal in a few hours. CONCLUSIONS: Pemetrexed can cause TTP.
      Clinicians have to be alert for the rapid onset and aggressiveness of this
      possible side effect. It is difficult to recognise the first signs and symptoms.

PMID- 25370902
TI  - Association of CYP3A4/5 genotypes and expression with the survival of patients
      with neuroblastoma.
AB  - Neuroblastoma (NB) is a rare pediatric disease in Lebanon for which poor
      prognosis remains a major challenge. Genetic polymorphism of genes coding for
      drug-metabolizing enzymes may influence the response of a patient to
      chemotherapy. This study investigates a possible association between CYP3A4/5
      polymorphism and expression levels and survival in NB patients. All patients with
      stage III and IV NB diagnosed between 1993 and 2012 in three major hospitals in
      Beirut were included (n=27). Demographic information and survival time were
      obtained from medical records. CYP3A4 and CYP3A5 genotypes and expression levels
      were determined in archival tumors by polymerase chain reaction (PCR) and
      restriction fragment length polymorphism and quantitative PCR, respectively.
      Additionally, MYCN amplification was assessed. A Cox proportional hazards model
      was used to evaluate potential associations, adjusting for MYCN amplification. A
      statistically significant increase in the risk of mortality was observed in
      patients with MYCN amplification [hazard ratio (HR) 4.11, 95% confidence interval
      (CI) 1.14-14.80]. Patients with CYP3A5 expression levels above the median had a
      lower risk of mortality (HR 0.61, 95% CI 0.21-1.74) and patients with CYP3A4
      expression levels above the median had a higher risk of mortality (HR 2.00, 95%
      CI 0.67-5.90). CYP3A5*3/*3 homozygote mutants had a 4.3-fold increase in the risk
      of mortality compared with that of homozygote wild-type or heterozygote mutants
      (HR 4.30, 95% CI 0.56-33.30). Carriers of the CYP3A4*1B mutant allele had a 52%
      lower risk of mortality compared with that of non-carriers (HR 0.48, 95% CI 0.06
      3.76). Although the results of the present study did not achieve statistical
      significance, associations were observed, which indicates that CYP3A4 and CYP3A5
      may modulate the clinical outcome of NB. Further studies with larger sample sizes
      are required to characterize the effects of the polymorphism and expression
      levels of CYP3A4/5 on the survival of patients with NB. 

PMID- 25370903
TI  - Competition in liver transplantation: helpful or harmful?
AB  - Improved outcomes of liver transplantation have led to increases in the numbers
      of US transplant centers and candidates on the list. The resultant and ever
      expanding organ shortage has created competition among centers, especially in
      regions with multiple liver transplant programs. Multiple reports now document
      that competition among the country's transplant centers has led to the listing of
      increasingly high-risk patients and the utilization of more marginal liver
      allografts. The transplant and medical communities at large should carefully re
      evaluate these practices and promote innovative approaches to restoring trust in
      the allocation of donor organs and confirming that there is nationwide conformity
      in the guidelines used for evaluating and listing potential candidates for this
      scarce resource.

PMID- 25370904
TI  - Effects of an intensive hog farming operation on groundwater in east
      Mediterranean (II): a study on K+, Na+, Cl -, PO43--P, Ca2+, Mg2+, Fe3+/Fe2+,
      Mn2+, Cu2+, Zn2+ and Ni2+.
AB  - The application of treated animal wastewater generated in concentrated animal
      feeding operations on surface soil (within farm borders) leads to degradation of
      groundwater. Effects of an intensive hog farming operation, located at a
      Mediterranean limestone soil coastal area, on groundwater were investigated.
      Treated animal wastewater was discharged on a small plot (~10.8 ha) with a
      geologic fault. Samples were taken from seven groundwater monitoring wells close
      to the farm. A significant increase of K(+), Na(+), Cl(-), PO4 (3-)-P, Ca(2+) and
      Mg(2+) concentrations was found in monitoring wells which are affected by the
      subsurface flow of groundwater. Concentrations of Fe(3+)/Fe(2+), Mn(2+), Cu(2+),
      Zn(2+) and Ni(2+) in all groundwater monitoring wells were extremely low. During
      the winter, significant increases in concentrations of K(+) and PO4 (3-)-P were
      noted and attributed to high precipitation, which assisted in the leaching of K
      and P to groundwater.

PMID- 25370905
TI  - The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles
      under flow conditions.
AB  - A rapid flow synthesis of oxazolines and their oxidation to the corresponding
      oxazoles is reported. The oxazolines are prepared at room temperature in a
      stereospecific manner, with inversion of stereochemistry, from beta-hydroxy
      amides using Deoxo-Fluor(r). The corresponding oxazoles can then be obtained via
      a packed reactor containing commercial manganese dioxide. 

PMID- 25370906
TI  - Validation of an immunochromatographic D-dimer test to presumptively identify
      menstrual fluid in forensic exhibits.
AB  - Identifying the biological source of a crime scene stain can be crucial for
      police investigations in many scenarios. Blood is one of the most common fluids
      found, and accurate differentiation between peripheral blood and menstrual fluid
      could provide valuable information regarding the issue of consent in sexual
      assault cases. For the detection of menstrual fluid, no easy-to-use presumptive
      test is available to date. Therefore, this study aimed to validate a simple
      immunochromatographic test for the indication of menstrual fluid, focusing on a D
      dimer assay. The Clearview(r) rapid D-dimer test provides a diagnostic assay for
      the detection of fibrin degradation products. We validated the sensitivity and
      robustness of the assay using fresh and dried menstrual fluid samples, body fluid
      mixtures, diluted samples, and casework swabs. Cross reactivity was tested for
      saliva, semen, vaginal fluid, and blood. No false positive results were obtained;
      it was possible to successfully analyze mixtures, highly diluted samples, and
      casework swabs. The results of this study indicate that the D-dimer assay
      reliably detects menstrual fluid in forensic exhibits and is easy to implement
      into the current workflow of body fluid identification. 

PMID- 25370907
TI  - Emergency review clinic: impact on paediatric admissions.
AB  - BACKGROUND: Inappropriate or unnecessary paediatric inpatient admissions are
      sometimes unavoidable but are costly and increase pressure on services. Various
      measures, including paediatric observation units, have been undertaken in an
      attempt to reduce these admissions. AIMS: We established an emergency review
      clinic to assess whether we could reduce admission rates by giving carefully
      selected children follow-up ED review appointments. METHODS: An emergency review
      clinic was run in the paediatric room of the Emergency Department by a senior
      paediatric registrar during the hours 10 a.m. to 12 midday, Monday to Friday
      inclusive. Patients were booked into this review clinic from ED. Data relating to
      paediatric admissions in the years prior to and after the institution of the
      review clinic were analysed. RESULTS: A significant reduction (p < 0.0001) was
      noted in the paediatric inpatient admission rates following establishment of the
      review clinic. CONCLUSIONS: A paediatric emergency review clinic can
      significantly reduce unnecessary or inappropriate admissions but more research is
      needed to quantitatively characterise parent/patient satisfaction in this regard.

PMID- 25370908
TI  - Hyponatraemia at hospital admission is a predictor of overall mortality.
AB  - BACKGROUND: Hyponatraemia is a prognostic marker of increased mortality and
      morbidity in selected groups of hospitalised patients. The aim of the present
      study was to examine the prevalence and prognostic significance of hyponatraemia
      at hospital admission in an unselected population with a broad spectrum of
      medical and surgical diagnoses. METHODS: Consecutive patients >40 years of age
      admitted to a general district hospital in Greater Copenhagen between 1 April
      1998 and 31 March 1999. Median follow-up time was 5.16 years (range 0-4372 days).
      Plasma sodium measurements were available in 2960 patients, and hyponatraemia
      defined as P-Na(+) <137 mmol/L at hospital admission was present in 1105 (37.3 %)
      patients. RESULTS: One-year mortality was higher for hyponatraemic patients than
      for normonatraemic patients: 27.5% versus 17.7%. Moreover, hyponatraemia was an
      independent predictor of short and long-term all-cause mortality after 1 year and
      after the entire observation period respectively: hazard ratio (HR) 1.6 (95 %
      confidence interval (CI) 1.4-1.9, P < 0.0001) and HR 1.4 (95 % CI 1.3-1.6, P <
      0.0001). Patients with hyponatraemia had longer hospitalisations than patients
      with normonatraemia: 7.6 (+/-0.38) days vs 5.6 (+/-0.21) days, P < 0.001. There
      was no interaction between hyponatraemia at admission and any admission diagnoses
      (P > 0.05 for all interaction analyses). CONCLUSION: Hyponatraemia is associated
      with increased all-cause mortality and longer admission length independently of
      diagnosis and clinical variables.

PMID- 25370909
TI  - Cohort study of Western Australia computed tomography utilisation patterns and
      their policy implications.
AB  - BACKGROUND: Computed tomography (CT) scanning is a relatively high radiation dose
      diagnostic imaging modality with increasing concerns about radiation exposure
      burden at the population level in scientific literature. This study examined the
      epidemiology of adult CT utilisation in Western Australia (WA) in both the public
      hospital and private practice settings, and the policy implications. METHODS:
      Retrospective cohort design using aggregate adult CT data from WA public
      hospitals and Medical Benefits Schedule (MBS) (mid-2006 to mid-2012). CT scanning
      trends by sex, age, provider setting and anatomical areas were explored using
      crude CT scanning rates, age-standardised CT scanning rates and Poisson
      regression modelling. RESULTS: From mid-2006 to mid-2012 the WA adult CT scanning
      rate was 129 scans per 1,000 person-years (PY). Females were consistently scanned
      at a higher rate than males. Patients over 65 years presented the highest
      scanning rates (over 300 scans per 1,000 PY). Private practice accounted for 73%
      of adult CT scans, comprising the majority in every anatomical area. In the
      private setting females predominately held higher age-standardised CT scanning
      rates than males. This trend reversed in the public hospital setting. Patients
      over 85 years in the public hospital setting were the most likely age group CT
      scanned in nine of ten anatomical areas. Patients in the private practice setting
      aged 85+ years were relatively less prominent across every anatomical area, and
      the least likely age group scanned in facial bones and multiple areas CT scans.
      CONCLUSION: In comparison to the public hospital setting, the MBS subsidised
      private sector tended to service females and relatively younger patients with a
      more diverse range of anatomical areas, constituting the majority of CT scans
      performed in WA. Patient risk and subsequent burden is greater for females, lower
      ages and some anatomical areas. In the context of a national health system,
      Australia has various avenues to monitor radiation exposure levels, improve
      physician training and modify funding mechanisms to ensure individual and
      population medical radiation exposure is as low as reasonably achievable.

PMID- 25370910
TI  - Update on a new controversy in endocrinology: isolated maternal hypothyroxinemia.
AB  - Isolated hypothyroxinemia (IH) is defined as a thyroxine level in the lower 5th
      (severe IH) or 10th percentile (mild IH) of the pregnancy-related reference range
      and a normal TSH. The etiology of IH remains unknown. This review aims to
      evaluate the biochemical criteria used to define IH in different published
      studies and to discuss potential maternal as well as fetal outcomes and whether
      treatment during early pregnancy can prevent the eventual adverse effects. For
      the current literature a better standardization of free thyroxine assays is
      needed, as well as the use of appropriated trimester-specific reference intervals
      for thyroid function tests. Today no study demonstrates a benefit from treating
      early pregnant IH women on perinatal and fetal outcomes. 

PMID- 25370911
TI  - Controllable Schottky barriers between MoS2 and permalloy.
AB  - MoS2 is a layered two-dimensional material with strong spin-orbit coupling and
      long spin lifetime, which is promising for electronic and spintronic
      applications. However, because of its large band gap and small electron affinity,
      a considerable Schottky barrier exists between MoS2 and contact metal, hindering
      the further study of spin transport and spin injection in MoS2. Although
      substantial progress has been made in improving device performance, the existence
      of metal-semiconductor Schottky barrier has not yet been fully understood. Here,
      we investigate permalloy (Py) contacts to both multilayer and monolayer MoS2.
      Ohmic contact is developed between multilayer MoS2 and Py electrodes with a
      negative Schottky barrier, which yields a high field-effect mobility exceeding 55
      cm(2)V(-1)s(-1) at low temperature. Further, by applying back gate voltage and
      inserting different thickness of Al2O3 layer between the metal and monolayer
      MoS2, we have achieved a good tunability of the Schottky barrier height (down to
      zero). These results are important in improving the performance of MoS2
      transistor devices; and it may pave the way to realize spin transport and spin
      injection in MoS2.

PMID- 25370912
TI  - Impact of biologic agents with and without concomitant methotrexate and at
      reduced doses in older rheumatoid arthritis patients.
AB  - OBJECTIVE: To examine whether concomitant methotrexate (MTX) use is associated
      with better biologic persistence and whether self-administered anti-tumor
      necrosis factor (anti-TNF) therapies are used at reduced doses in real-world
      clinical care settings, not just clinical trials. METHODS: We conducted a
      retrospective cohort study among rheumatoid arthritis (RA) patients using
      Medicare claims data from 2006 to 2012. Subjects were new initiators of
      etanercept, infliximab, adalimumab, abatacept, and tocilizumab with at least 12
      months of continuous medical and pharmacy coverage after treatment initiation. We
      examined the association between concomitant MTX use and persistence on biologic
      agents using Cox proportional hazards regression, adjusting for demographics and
      baseline comorbidities. We further identified a subgroup of patients who
      initiated and were adherent on etanercept or adalimumab for at least 12 months
      and examined the proportion of patients who subsequently used these therapies at
      reduced doses continuously for an additional 12, 18, and 24 months. RESULTS: Of
      26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall,
      patients who initiated biologic monotherapy were 1.4 (95% confidence interval
      [95% CI] 1.3-1.5) times more likely to discontinue at 1 year compared to those
      who initiated combination therapy, and 1.8 (95% CI 1.7-2.0) times more likely if
      starting infliximab monotherapy. Approximately 10-20% of patients who initiated
      and adhered to etanercept and adalimumab for >=12 months subsequently received
      reduced-dose therapy for an 12 additional months and beyond. CONCLUSION: In real
      world practice, concomitant MTX was associated with improved persistence on
      biologic therapy, especially for infliximab users; reduced-dose injectable anti
      TNF therapy was used by a substantial proportion of RA patients.

PMID- 25370914
TI  - 10-year survival rate and the incidence of peri-implant disease of 374 titanium
      dental implants with a SLA surface: a prospective cohort study in 177 fully and
      partially edentulous patients.
AB  - PURPOSE: This prospective cohort study evaluates the 10-year survival and
      incidence of peri-implant disease at implant and patient level of sandblasted,
      large grid, and acid-etched titanium dental implants (Straumann, soft tissue
      level, SLA surface) in fully and partially edentulous patients. MATERIAL AND
      METHODS: Patients who had dental implant surgery in the period between November
      1997 and June 2001, with a follow-up of at least 10 years, were investigated for
      clinical and radiological examination. Among the 506 inserted dental implants in
      250 patients, 10-year data regarding the outcome of implants were available for
      374 dental implants in 177 patients. In the current study, peri-implantitis was
      defined as advanced bone loss (?1.5 mm. postloading) in combination with bleeding
      on probing. RESULTS: At 10-year follow-up, only one implant was lost (0.3%) 2
      months after implant surgery due to insufficient osseointegration. The average
      bone loss at 10 year postloading was 0.52 mm. Advanced bone loss at 10-year
      follow-up was present in 35 dental implants (9.8%). Seven percent of the observed
      dental implants showed bleeding on probing in combination with advanced bone loss
      and 4.2% when setting the threshold for advanced bone loss at 2.0 mm. Advanced
      bone loss without bleeding on probing was present in 2.8% of all implants.
      CONCLUSION: In this prospective study, the 10-year survival rate at implant and
      patient level was 99.7% and 99.4%, respectively. Peri-implantitis was present in
      7% of the observed dental implants according to the above-mentioned definition of
      peri-implantitis. This study shows that SLA implants offer predictable long-term
      results as support in the treatment of fully and partially edentulous patients.

PMID- 25370913
TI  - Postprandial glucose metabolism and SCFA after consuming wholegrain rye bread and
      wheat bread enriched with bioprocessed rye bran in individuals with mild
      gastrointestinal symptoms.
AB  - BACKGROUND: Rye bread benefits glucose metabolism. It is unknown whether the same
      effect is achieved by rye bran-enriched wheat bread. We tested whether white
      wheat bread enriched with bioprocessed rye bran (BRB + WW) and sourdough
      wholegrain rye bread (WGR) have similar effects on glucose metabolism and plasma
      level of short chain fatty acids (SCFAs). METHODS: Twenty-one (12 women) of 23
      recruited subjects completed an intervention with a four-week run-in and two four
      week test periods in cross-over design. White wheat bread (WW; 3% fibre) was
      consumed during the run-in, and WGR and BRB + WW (10% fibre) during the test
      periods. A meal test providing 51/33/11 E % from carbohydrates/fat/protein was
      conducted at the end of each period. Fasting and postprandial plasma samples were
      analysed for glucose, insulin, and SCFA. RESULTS: Glucose and insulin responses
      and plasma concentrations of SCFAs to the meal test were similar between the WGR
      and BRB + WW periods. When compared to the WW period, postprandial insulin
      concentration at 120 min was lower (p = 0.023) and the first-phase insulin
      secretion improved (p = 0.033) only after the WGR period, whereas postprandial
      concentrations of butyrate (p < 0.05) and propionate (p = 0.009) at 30 min
      increased during both rye bread periods. CONCLUSIONS: Beneficial effects of WGR
      over white wheat bread on glucose and SCFA production were confirmed. The
      enrichment of the white wheat bread with bioprocessed rye bran (BRB + WW) yielded
      similar but not as pronounced effects than WGR when compared to WW alone.
      Postprandially measured glucose metabolism and concentrations of SCFAs provided
      additional information along with fasting measurements.

PMID- 25370915
TI  - Changes in muscle proteomics in the course of the Caudwell Research Expedition to
      Mt. Everest.
AB  - This study employed differential proteomic and immunoassay techniques to
      elucidate the biochemical mechanisms utilized by human muscle (vastus lateralis)
      in response to high altitude hypoxia exposure. Two groups of subjects,
      participating in a medical research expedition (A, n = 5, 19 d at 5300 m
      altitude; B, n = 6, 66 d up to 8848 m) underwent a ~ 30% drop of muscular
      creatine kinase and of glycolytic enzymes abundance. Protein abundance of most
      enzymes of the tricarboxylic acid cycle and oxidative phosphorylation was reduced
      both in A and, particularly, in B. Restriction of alpha-ketoglutarate toward
      succinyl-CoA resulted in increased prolyl hydroxylase 2 and glutamine synthetase.
      Both A and B were characterized by a reduction of elongation factor 2 alpha,
      controlling protein translation, and by an increase of heat shock cognate 71 kDa
      protein involved in chaperone-mediated autophagy. Increased protein levels of
      catalase and biliverdin reductase occurred in A alongside a decrement of voltage
      dependent anion channels 1 and 2 and of myosin-binding protein C, suggesting
      damage to the sarcomeric structures. This study suggests that during
      acclimatization to hypobaric hypoxia the muscle behaves as a producer of
      substrates activating a metabolic reprogramming able to support anaplerotically
      the tricarboxylic acid cycle, to control protein translation, to prevent energy
      expenditure and to activate chaperone-mediated autophagy.

PMID- 25370918
TI  - Differential field responses of the little fire ant, Wasmannia auropunctata
      (Roger), to alarm pheromone enantiomers.
AB  - The little fire ant, Wasmannia auropunctata (Roger) (Hymenoptera: Formicidae), is
      an invasive ant with negative impacts on both biodiversity and agriculture
      throughout the tropics and subtropics. Field experiments were conducted in order
      to elucidate the relative attractiveness of the enantiomers of the alarm
      pheromones, 2,5-dimethyl-3-(2-methylbutyl)pyrazine and 3-methyl-2-(2
      methylbutyl)pyrazine. The enantiomers tested were synthesized from commercially
      available (S)-2-methylbutan-1-ol or kinetically resolved (R)-2-methylbutan-1-ol,
      prepared using Pseudomonas cepacia lipase (PCL). Bioassays conducted in a
      macadamia orchard on the island of Hawaii demonstrated that W. auropunctata were
      preferentially attracted to the (S)-enantiomers of both alkyl pyrazines over the
      racemic mixtures in all experiments. To our knowledge, this is the first instance
      of differential attraction of ants to the enantiomers of chiral pyrazine
      pheromones despite many examples of these compounds in the literature. In
      addition, using a chiral column it was determined that (S)-2,5-dimethyl-3-(2
      methylbutyl)pyrazine and (S)-3-methyl-2-(2-methylbutyl)pyrazine are the only
      enantiomers produced by W. auropunctata. 

PMID- 25370917
TI  - MCP-1 and CCR2 gene polymorphisms in Parkinson's disease in a Han Chinese cohort.
AB  - Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC chemokine receptor
      2 (CCR2) play important roles in neuroinflammation and they have been shown to be
      involved in Parkinson's disease (PD) pathogenesis. In addition, several studies
      have suggested a role for the MCP-1 and CCR2 genotypes in cognitive impairment
      and depression, which are common non-motor symptoms in PD patients. In this
      study, a cohort of 521 PD patients and 556 cases of healthy controls were
      recruited to investigate the association between the MCP-1 2518A/G (rs1064211)
      and CCR2 V64I (rs1799864) gene polymorphisms and PD risk in the Chinese
      population. We also analyze the influence of these genotypes on the cognitive
      function and depression in PD patients by comparing Mini-Mental State Examination
      (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale
      Chinese Revision (WAIS-RC), Wechsler Memory Scale-Chinese Revision (WMS-RC) and
      Hamilton Depression Rating Scale (HAMD) ratings in 217 PD patients. Our results
      showed no significant differences in the genotype frequency between the PD group
      and the control group (P > 0.05). In addition, we also failed to find an
      influence of the MCP-1 and CCR2 genotypes on MMSE scores, MoCA scores, WAIS-RC
      scores, WMS-RC scores and HAMD scores in PD patients (P > 0.05). The MCP-1 and
      CCR2 gene polymorphisms may not be genetic risk factors for PD in the Han Chinese
      population, and they do not appear to influence cognitive function and depression
      in PD patients.

PMID- 25370916
TI  - Association between ubiquitin carboxy-terminal hydrolase-L1 S18Y variant and risk
      of Parkinson's disease: the impact of ethnicity and onset age.
AB  - The Ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) is a candidate risk gene for
      Parkinson' disease (PD), and a function SNP (rs5030732) in the coding region of
      this gene has been studied for the association with the disease extensively among
      worldwide populations, but the results were inconsistent and controversial. Here,
      to estimate the association between UCHL1 S18Y polymorphism and risk of PD in
      general population, we conducted a systematic meta-analysis by combining all
      available case-control subjects in Asian, European, and American populations,
      with a total of 7742 PD cases and 8850 healthy controls, and the pooled odds
      ratios (ORs) and 95% confidence intervals (95% CIs) for UCHL1 S18Y polymorphism
      and PD were calculated using the Mantel-Haenszel method with a fixed- or random
      effects model. Subgroup analysis was also performed in different onset age
      matched groups. Among high-quality studies, UCHL1 S18Y polymorphism was
      moderately associated with the risk of PD (allele contrasts, OR = 1.063, 95% CI
      1.008-1.122; p = 0.024; regressive genetic model, OR = 1.078, 95% CI 1.005-1.157;
      p = 0.035). When stratifying for ethnicity, none association were observed in
      subgroups. Analysis of early-onset PD (EOPD) and late-onset PD (LOPD) revealed
      that the polymorphism was not associated with the risk of PD. In conclusion, our
      meta-analysis suggests that UCHL1 S18Y polymorphism is moderately associated with
      susceptibility to PD, and more studies are needed to confirm our conclusion.

PMID- 25370919
TI  - Early-onset pseudoxanthoma elasticum-like papillary dermal elastolysis.

PMID- 25370920
TI  - siRNA-mediated knockdown against NUF2 suppresses pancreatic cancer proliferation
      in vitro and in vivo.
AB  - NUF2 (NUF2, Ndc80 kinetochore complex component) plays an important role in
      kinetochore-microtubule attachment. It has been reported that NUF2 is associated
      with multiple human cancers. However, the functional role of NUF2 in pancreatic
      cancer remains unclear. In this study, we found that NUF2 expression was stronger
      in tumour tissues than in normal pancreatic tissues, and its overexpression could
      be related to poor prognosis. Moreover, NUF2 was highly expressed in several
      human pancreatic cancer cell lines. We took advantage of lentivirus-mediated
      siRNA (small interfering RNA) to suppress NUF2 expression in PANC-1 and Sw1990
      cell lines aiming to investigate the role of NUF2 in pancreatic cancer. NUF2
      silencing by RANi (RNA interference) reduced the proliferation and colony
      formation ability of pancreatic cancer cells in vitro. Cell cycle analysis showed
      that NUF2 knockdown induced cell cycle arrest at G0/G1 phase via suppression of
      Cyclin B1, Cdc2 and Cdc25A. More importantly, NUF2 silencing was able to
      alleviate in vivo tumourigenesis in pancreatic cancer xenograft nude mice.
      Collectively, the present study indicates that the siRNA-mediated knockdown
      against NUF2 may be a promising therapeutic method for the treatment of
      pancreatic cancer.

PMID- 25370921
TI  - Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds
      and Immune Responses in a Rat Model of Incisional Pain.
AB  - The aim of this study was to elucidate the antinociceptive interaction between
      cannabinoids and tramadol and their impact on proinflammatory response, in terms
      of serum intereleukin-6 (IL-6) and interleukin-2 (IL-2) release, in a rat model
      of incisional pain. Prospective randomized trial assessing the individual or
      combined application of intraperitoneal tramadol (10 mg/kg) and the selective
      cannabinoid-2 (CB-2) agonist (R,S)-AM1241 (1 mg/kg) applied postsurgical stress
      stimulus. Pharmacological specificity was established by antagonizing tramadol
      with naloxone (0.3 mg/kg) and (R,S)-AM1241 with SR144528 (1 mg/kg). Thermal
      allodynia was assessed by hot plate test 30 (T30), 60 (T60), and 120 (T120)
      minutes after incision. Blood samples for plasma IL-6 and IL-2 level
      determination were obtained 2 hours after incision. Data from 42 rats were
      included in the final analyses. Significant augmentation of thermal threshold was
      observed at all time points, after administration of either tramadol or (R,S)
      AM1241 compared with the control group (P = 0.004 and P = 0.015, respectively).
      The combination of (R,S)-AM1241 plus tramadol promoted the induced
      antinociception in an important manner compared with control (P = 0.002) and
      (R,S)-AM1241 (P = 0.022) groups. Although the antiallodynic effect produced by
      tramadol was partially reversed by naloxone 30 and 60 minutes after incision (P =
      0.028 and P = 0.016, respectively), SR144528 blocked the effects of (R,S)-AM1241
      administration in a significant manner (P = 0.001) at all time points. Similarly,
      naloxone plus SR144528 also blocked the effects of the combination of (R,S)
      AM1241 with tramadol at all time points (P = 0.000). IL-6 level in (R,S)-AM1241
      plus tramadol group was significantly attenuated compared with control group (P =
      0.000). Nevertheless, IL-2 levels remained unchanged in all experimental groups.
      It seems that the concomitant administration of a selective CB-2 agonist with
      tramadol in incisional pain model may improve antinociceptive effects and immune
      responses of cannabinoids, but this effect does not seem to be superior to that
      of tramadol alone.

PMID- 25370922
TI  - Electronic Capture of Written Handoff Information: What Are the Next Steps?
AB  - Communication lapses during patient care transitions are reported to be frequent
      and may result in patient harm. The primary objective of our study was to assess
      the completeness, accuracy, and usefulness of our electronic handoff system to
      guide future software changes and educational interventions. We randomly selected
      and reviewed 707 of 2840 available handoff records generated on the medicine
      service of an academic medical center between August 1, 2012 and December 31,
      2012. We used both quantitative and qualitative analytical techniques to
      characterize sign-outs in the following dimensions: completeness, usefulness and
      accuracy of information content, handoff task category, logic, internal
      consistency and appropriateness of assigned tasks, and composition and complexity
      of assigned tasks. The degree of completeness of information varied considerably
      across domains. Completeness was highest for entry of assigned tasks (99.9%),
      nearly as high for hospital course/presenting illness (95%), and relatively high
      (87%-98%) for entry of provider name and contact information, principal
      diagnosis, allergies, current clinical condition, mental status, and code status.
      Eighty-eight percent written handoffs described clinical condition and hospital
      course and whether there were tasks to complete. In 58% of suitable records, all
      problems listed in the electronic health record (EHR) were also present in the
      history of present illness. The accuracy of entered information also displayed
      wide variation. Only 80% of cardiovascular medications matched the
      contemporaneous EHR pharmacy record. Birth dates and allergies were identical in
      the handoff system and EHR in 95% and 86% of respective records. Of assigned
      tasks, 8% contained at least 1 unnecessary component or illogical/internally
      inconsistent element. Use of a handoff system, which organizes information entry
      through a standard template, promotes completeness of written handoff
      information. Inaccuracies in handoff data are associated with manual entry and
      should be discouraged. Programs should be encouraged to develop robust interfaces
      between the EHR and handoff platforms to promote entry of complete and accurate
      data and to enhance provider workflow. 

PMID- 25370923
TI  - Incremental Blood Pressure-Lowering Effect of Titrating Amlodipine for the
      Treatment of Hypertension in Patients Including Those Aged >=55 Years.
AB  - Small reductions in blood pressure reduce the risk of cardiovascular events.
      Here, we report 2 post hoc pooled analyses assessing the antihypertensive effect
      of amlodipine in patients who had not responded to 5 mg and were uptitrated to 10
      mg. The first analysis assessed subgroups of patients aged either younger than 55
      years or 55 years or older and the second analysis pooled all patients
      irrespective of age. Of 706 patients in the age-related analysis, a statistically
      significant decrease in blood pressure from baseline was observed {for younger
      than 55 years [N = 253]: systolic blood pressure = -12.8 [standard error (SE) =
      0.90] mm Hg, diastolic blood pressure = -8.0 [SE = 0.55] mm Hg; for 55 years or
      older [N = 453]: systolic blood pressure = -12.1 [SE = 0.66] mm Hg, diastolic
      blood pressure = -6.7 [SE = 0.39] mm Hg; all P < 0.0001}. In total, 45.8% and
      39.3% of patients aged younger than 55 and 55 years or older, respectively,
      achieved their blood pressure goals. Adverse events were experienced by 62
      (24.5%) patients aged younger than 55 years and 136 (30.0%) patients aged 55
      years or older. Similar efficacy and safety results were seen in the all patient
      pooled analysis. Titration of amlodipine from 5 mg to 10 mg significantly
      decreased blood pressure in older hypertensive patients, which is clinically
      relevant because increased age is associated with hypertension and cardiovascular
      events. 

PMID- 25370924
TI  - Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome--a case
      control study.
AB  - Bernard-Soulier syndrome (BSS) is a rare severe autosomal recessive bleeding
      disorder. To date heterozygous carriers of BSS mutations have not been shown to
      have bleeding symptoms. We assessed bleeding using a semi-quantitative
      questionnaire, platelet parameters, PFA-100 closure times, ristocetin response,
      GP Ib/IX expression and VWF antigen in 14 BSS patients, 30 heterozygote carriers
      for related mutations and 29 controls. Eight mutations in GP1BA, GP1BB or GP9
      were identified including four previously unknown pathogenic mutations. Subjects
      with BSS reported markedly more mucocutaneous bleeding than controls. Increased
      bleeding was also observed in heterozygotes. Compared to controls, patients with
      BSS had lower optical platelet counts (P < 0.001), CD61-platelet counts (P <
      0.001) and higher mean platelet volume (17.7 vs. 7.8 fL, P < 0.001) and
      ristocetin response and closure times were unmeasurable. Heterozygotes had higher
      MPV (9.7 fL, P < 0.001) and lower platelet counts (P < 0.001) than controls but
      response to ristocetin and closure times were normal. The VWF was elevated in
      both BSS and in heterozygotes (P = 0.005). We conclude that heterozygotes for BSS
      mutations have lower platelet counts than controls and show a bleeding phenotype
      albeit much milder than in BSS. Both patients with BSS and heterozygote carriers
      of pathogenic mutations have raised VWF.

PMID- 25370925
TI  - Pharmacokinetics, phenotype and product choice in haemophilia B: how to strike a
      balance?
AB  - At the 7th Annual Congress of the European Association for Haemophilia and Allied
      Disorders (EAHAD) held in Brussels, Belgium, in February 2014, Pfizer sponsored a
      satellite symposium entitled: "Pharmacokinetics, phenotype and product choice in
      haemophilia B: How to strike a balance?" Co-chaired by Cedric Hermans (Cliniques
      Universitaires Saint Luc, Brussels, Belgium) and Mike Laffan (Imperial College,
      London, UK), the symposium provided an opportunity to debate whether
      pharmacokinetic (PK) parameters are good surrogates for clinical efficacy for
      haemophilia B in clinical practice, consider the perceptions and evidence of
      disease severity, and examine how these considerations can inform approaches to
      balancing the potential risks and benefits of the currently available treatment
      options for haemophilia B. PK parameters are routinely measured in clinical
      practice and are a requirement of regulatory bodies to demonstrate the clinical
      efficacy of products; however, the relationship between measured PK parameters
      and clinical efficacy is yet to be determined, an issue that was debated by Gerry
      Dolan (University Hospital, Queen's Medical Centre, Nottingham, UK) and Erik
      Berntorp (Lund University, Malmo Centre for Thrombosis and Haemostasis, Malmo,
      Sweden). Elena Santagostino (Universita degli Studi di Milano, Milano, Italy)
      reviewed how differing perceptions on the severity of haemophilia B compared with
      haemophilia A may have an impact on clinical decision-making. Finally, Andreas
      Tiede (Hannover Medical School, Hannover, Germany), examined the considerations
      for balancing the potential risks and benefits of the currently available
      treatment options for haemophilia B. Although the pathophysiology of haemophilia
      B has been widely studied and is largely understood, continued investigation and
      discussion around the optimal management course and appropriate therapeutic
      choice is warranted. 

PMID- 25370926
TI  - A comparison of principal component regression and genomic REML for genomic
      prediction across populations.
AB  - BACKGROUND: Genomic prediction faces two main statistical problems:
      multicollinearity and n ? p (many fewer observations than predictor variables).
      Principal component (PC) analysis is a multivariate statistical method that is
      often used to address these problems. The objective of this study was to compare
      the performance of PC regression (PCR) for genomic prediction with that of a
      commonly used REML model with a genomic relationship matrix (GREML) and to
      investigate the full potential of PCR for genomic prediction. METHODS: The PCR
      model used either a common or a semi-supervised approach, where PC were selected
      based either on their eigenvalues (i.e. proportion of variance explained by SNP
      (single nucleotide polymorphism) genotypes) or on their association with
      phenotypic variance in the reference population (i.e. the regression sum of
      squares contribution). Cross-validation within the reference population was used
      to select the optimum PCR model that minimizes mean squared error. Pre-corrected
      average daily milk, fat and protein yields of 1609 first lactation Holstein
      heifers, from Ireland, UK, the Netherlands and Sweden, which were genotyped with
      50 k SNPs, were analysed. Each testing subset included animals from only one
      country, or from only one selection line for the UK. RESULTS: In general,
      accuracies of GREML and PCR were similar but GREML slightly outperformed PCR.
      Inclusion of genotyping information of validation animals into model training
      (semi-supervised PCR), did not result in more accurate genomic predictions. The
      highest achievable PCR accuracies were obtained across a wide range of numbers of
      PC fitted in the regression (from one to more than 1000), across test populations
      and traits. Using cross-validation within the reference population to derive the
      number of PC, yielded substantially lower accuracies than the highest achievable
      accuracies obtained across all possible numbers of PC. CONCLUSIONS: On average,
      PCR performed only slightly less well than GREML. When the optimal number of PC
      was determined based on realized accuracy in the testing population, PCR showed a
      higher potential in terms of achievable accuracy that was not capitalized when PC
      selection was based on cross-validation. A standard approach for selecting the
      optimal set of PC in PCR remains a challenge.

PMID- 25370927
TI  - mAb806 binding to epidermal growth factor receptor: a computational study.
AB  - The epidermal growth factor receptor (EGFR) is an important target in the
      treatment of cancer. A very potent antibody, mAb806, has been developed against
      overexpressed EGFR and was found to be particularly active in brain tumors.
      Structural studies reveal that it binds to an epitope on the extracellular region
      of the EGFR. However, this epitope is cryptic/buried in crystal structures of the
      active (untethered) and inactive (tethered) EGFR, and it is unclear as to how the
      antibody interacts with this region. To explore this interaction, we combined
      molecular docking, steered molecular dynamics, and equilibrium molecular dynamics
      simulations. Our computational models reveal that the antibody induces local
      unfolding around the epitope to form the antibody-EGFR complex. In addition,
      regions in the vicinity of the epitope also modulate the interaction, which are
      in accordance with several other known antibody-antigen interactions, and offers
      new possibilities for the design of antibodies with increased potency and
      specificity for this receptor.

PMID- 25370928
TI  - Cotton (Gossypium hirsutum) 14-3-3 proteins participate in regulation of fibre
      initiation and elongation by modulating brassinosteroid signalling.
AB  - Cotton (Gossypium hirsutum) fibre is an important natural raw material for
      textile industry in the world. Understanding the molecular mechanism of fibre
      development is important for the development of future cotton varieties with
      superior fibre quality. In this study, overexpression of Gh14-3-3L in cotton
      promoted fibre elongation, leading to an increase in mature fibre length. In
      contrast, suppression of expression of Gh14-3-3L, Gh14-3-3e and Gh14-3-3h in
      cotton slowed down fibre initiation and elongation. As a result, the mature
      fibres of the Gh14-3-3 RNAi transgenic plants were significantly shorter than
      those of wild type. This 'short fibre' phenotype of the 14-3-3 RNAi cotton could
      be partially rescued by application of 2,4-epibrassinolide (BL). Expression
      levels of the BR-related and fibre-related genes were altered in the Gh14-3-3
      transgenic fibres. Furthermore, we identified Gh14-3-3 interacting proteins
      (including GhBZR1) in cotton. Site mutation assay revealed that Ser163 in GhBZR1
      and Lys51/56/53 in Gh14-3-3L/e/h were required for Gh14-3-3-GhBZR1 interaction.
      Nuclear localization of GhBZR1 protein was induced by BR, and phosphorylation of
      GhBZR1 by GhBIN2 kinase was helpful for its binding to Gh14-3-3 proteins.
      Additionally, 14-3-3-regulated GhBZR1 protein may directly bind to GhXTH1 and
      GhEXP promoters to regulate gene expression for responding rapid fibre
      elongation. These results suggested that Gh14-3-3 proteins may be involved in
      regulating fibre initiation and elongation through their interacting with GhBZR1
      to modulate BR signalling. Thus, our study provides the candidate intrinsic genes
      for improving fibre yield and quality by genetic manipulation. 

PMID- 25370930
TI  - Asymmetric enamine catalysis with beta-ketoesters by chiral primary amine:
      divergent stereocontrol modes.
AB  - alpha-Branched ketones remain a challenging type of substrates in aminocatalysis
      due to their congested structures as well as the associated difficulties in
      controlling chemo- and stereoselectivity. In this work, we have explored
      asymmetric aminocatalysis with alpha-substituted beta-ketoesters. A simple chiral
      primary amine catalyst was identified to enable unprecedentedly effective
      catalysis of beta-ketoesters in alpha-hydrazination and Robinson annulation
      reaction with good yields and high enantioselectivities. Stoichiometric
      experiments with preformed enamine ester intermediates revealed their enamine
      catalytic nature as well as the critical roles of acidic additives in
      facilitating catalytic turnovers and in tuning the chemo- and stereoselectivity.
      With the identical catalytic system, the two reactions demonstrated opposite
      chiral inductions in terms of the absolute configurations of the newly formed
      stereogenic centers. Investigations into this intriguing issue by DFT have
      revealed divergent stereocontrol modes. For alpha-hydrazination, H-bonding
      directed facial attack determines the stereoselectivity, whereas a steric model
      is applied to the Robinson annulation where dual activations of both beta
      ketoester and vinyl ketone/aldehyde are involved. 

PMID- 25370929
TI  - Conditioned medium derived from notochordal cell-rich nucleus pulposus tissue
      stimulates matrix production by canine nucleus pulposus cells and bone marrow
      derived stromal cells.
AB  - OBJECTIVES: Conditioned medium derived from notochordal cell-rich nucleus
      pulposus tissue (NCCM) was previously shown to have a stimulatory effect on bone
      marrow stromal cells (BMSCs) and nucleus pulposus cells (NPCs) individually, in
      mixed species in vitro cell models. The objective of the current study was to
      assess the stimulatory effect of NCCM on NPCs in a homologous canine in vitro
      model and to investigate whether combined stimulation with NCCM and addition of
      BMSCs provides a synergistic stimulatory effect. METHODS: BMSCs and NPCs were
      harvested from chondrodystrophic dogs with confirmed early intervertebral disc
      (IVD) degeneration. NCCM was produced from NP tissue of nonchondrodystrophic dogs
      with healthy IVDs. BMSCs or NPCs alone (3*10(6) cells/mL) and NPCs+BMSCs (6*10(6)
      cells/mL; mixed 1:1) were cultured for 4 weeks in 1.2% alginate beads under base
      medium (BM), NCCM, or with addition of 10 ng/mL transforming growth factor-beta1
      (TGF-beta1) as a positive control. Beads were assessed for glycosaminoglycan
      (GAG) and DNA contents by biochemical assays, GAG deposition by Alcian blue
      staining, and gene expression (aggrecan, versican, collagen 1 and 2, SOX9, A
      disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and
      matrix metalloproteinase 13 [MMP13]) with real-time quantitative RT-PCR. RESULTS:
      NCCM increased NPC proliferation, proteoglycan production, and expression of
      genes associated with a healthy NP-like phenotype. BMSCs also showed increased
      proteoglycan production under NCCM, but these effects were not observed at the
      gene level. Combined stimulation of NPCs with NCCM and coculturing with BMSCs did
      not result in increased proteoglycan content compared to stimulation with NCCM
      alone. DISCUSSION: NCCM stimulates matrix production by both NPCs and BMSCs and
      directs NPCs toward a healthier phenotype. NCCM is therefore promising for IVD
      regeneration and identification of the bioactive components will be helpful to
      further develop this approach. In the current study, no synergistic effect of
      adding BMSCs was observed.

PMID- 25370931
TI  - Absolute immature platelet count dynamics in diagnosing and monitoring the
      clinical course of thrombotic thrombocytopenic purpura.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening
      diagnosis requiring prompt initiation of therapeutic plasma exchange (TPE).
      Measurement of immature platelet (PLT) fraction (%-IPF) differentiates PLT
      consumption or destruction from hypoproduction. STUDY DESIGN AND METHOD: Our
      study evaluated %-IPF changes over the course of TTP treated with TPE and as a
      measure of treatment efficacy. Eleven idiopathic TTP patients, two human
      immunodeficiency virus (HIV)-associated TTP patients, and five non-TTP patients
      with thrombocytopenia were enrolled into our study. All patients were treated
      with TPE and had ADAMTS13 activity measured. RESULTS: All idiopathic TTP patients
      had a significantly increased %-IPF and decreased absolute immature PLT count (A
      IPC) and PLT count at presentation. An A-IPC value of less than 5 * 10(9) /L at
      presentation has 84.6% sensitivity, 80% specificity, and 91.7% positive
      predictive value for diagnosing TTP. A concurrent steady decline in %-IPF and
      increased PLT counts toward normal was observed in TTP patients undergoing TPE.
      The A-IPC, however, showed an increase and decrease curve that was not seen in
      the two HIV-associated TTP patients with no response to TPE and the five non-TTP
      patients. More importantly, reaching an A-IPC ratio of 3 compared to baseline
      value during TPE can readily differentiate idiopathic TTP from the other two
      groups and is correlated with good clinical responses to TPE. An abrupt increase
      of A-IPC during TPE was also noted in a TTP patient who relapsed 3 days before
      PLT count decrease. A-IPC is positively correlated with ADAMTS13 activity at
      presentation but negatively correlated with ADAMTS13 activity during recovery.
      CONCLUSION: A-IPC should be routinely analyzed for diagnosing and monitoring TTP
      patients.

PMID- 25370932
TI  - Role of Mitochondrial Calcium Uniporter in Early Brain Injury After Experimental
      Subarachnoid Hemorrhage.
AB  - Previous studies have shown that mitochondrial Ca(2+) is undertaken by
      mitochondrial calcium uniporter (MCU), and its accumulation is associated with
      the development of many diseases. However, little was known about the role of MCU
      in early brain injury (EBI) after subarachnoid hemorrhage (SAH). MCU can be
      opened by spermine under a physiological condition and inhibited by ruthenium red
      (RR). Herein, we investigated the effects of RR and spermine to reveal the role
      of MCU in SAH animal model. The data obtained with biochemical and histological
      assays showed that mitochondrial Ca(2+) concentration was significantly increased
      in the temporal cortex of rats 1, 2, and 3 days after SAH, consistent with
      constant high levels of cellular Ca(2+) concentration. In agreement with the
      observation in the acute phase, SAH rats showed an obvious increase of reactive
      oxygen species (ROS) level and decrease of ATP production. Blockage of MCU
      prevented Ca(2+) accumulation, abated the level of oxidative stress, and improved
      the energy supply. Translocation of cytochrome c, increased cleaved caspase-3,
      and a large amount of apoptotic cells after SAH were reversed by RR
      administration. Surprisingly, exogenous spermine did not increase cellular Ca(2+)
      concentration, but lessened the Ca(2+) accumulation after SAH to benefit the
      rats. Taken together, our results demonstrated that blockage of MCU or prevention
      of Ca(2+) accumulation after SAH is essential in EBI after SAH. These findings
      suggest that MCU is considered to be a therapeutic target for patients suffering
      from SAH.

PMID- 25370933
TI  - Identifying the Association Between Alzheimer's Disease and Parkinson's Disease
      Using Genome-Wide Association Studies and Protein-Protein Interaction Network.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second
      most common neurodegenerative diseases in the elderly. Shared clinical and
      pathological features have been reported. Recent large-scale genome-wide
      association studies (GWAS) have been conducted and reported a number of AD and PD
      variants. Until now, the underlying genetic mechanisms for all these newly
      identified PD variants as well as the association between AD and PD are still
      unclear exactly. We think that PD variants may contribute to AD and PD by
      influence on brain gene expression. Here, we conducted a systems analysis using
      (1) AD and PD variants (P < 5.00E-08) identified by the published GWAS; (2) four
      brain expression GWAS datasets using expression quantitative trait loci from the
      cerebellum and temporal cortex; (3) large-scale AD GWAS from the Alzheimer
      Disease Genetics Consortium (ADGC); (4) a protein-protein interaction network.
      Our results indicated that PD variants around the 17q21 were associated with gene
      expression and suggestive AD risk. We also identified significant interaction
      among AD and PD susceptibility genes. We believe that our findings may explain
      the underlying genetic mechanisms for newly identified PD variants in PD and AD,
      as well as the association between AD and PD, which may be very useful for future
      genetic studies for both diseases. 

PMID- 25370934
TI  - Cyclosporine A and MnTMPyP Alleviate alpha-Synuclein Expression and Aggregation
      in Cypermethrin-Induced Parkinsonism.
AB  - Cypermethrin induces the mitochondrial dysfunction and oxidative damage to the
      nigrostriatal dopaminergic neurons leading to Parkinsonism in rats. Despite alpha
      synuclein aggregation is reported to be critical in Parkinson's disease, its role
      and alliance with the mitochondrial dysfunction and oxidative damage leading to
      cypermethrin-induced Parkinsonism have not yet been deciphered. The present study
      aimed to examine the effect of cypermethrin on the expression and aggregation of
      alpha-synuclein and its subsequent connection with oxidative damage and
      mitochondrial dysfunction leading to the nigrostriatal dopaminergic
      neurodegeneration in the presence or absence of a mitochondrial membrane
      transition pore opening inhibitor, cyclosporine A and a superoxide
      dismutase/catalase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl)
      porphyrin pentachloride (MnTMPyP). The expression of alpha-synuclein, 3
      nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE)-modified proteins, mitochondrial
      dysfunction-dependent apoptotic proteins, nitrite content, lipid peroxidation
      (LPO) and number of tyrosine hydroxylase (TH)-positive neurons were estimated in
      the substantia nigra and dopamine content in the striatum of control and treated
      rats employing standard procedures. Cypermethrin augmented the expression of
      alpha-synuclein, 3-NT, 4-HNE-modified proteins, caspase-3, mitochondrial Bax and
      cytosolic cytochrome-c along with nitrite and LPO and reduced the expression of
      cytosolic Bax, mitochondrial cytochrome-c, dopamine and number of TH-positive
      neurons. Cyclosporine A or MnTMPyP alleviated the expression and aggregation of
      alpha-synuclein along with indicators of the mitochondrial dysfunction, oxidative
      damage and dopaminergic neurodegeneration. The results demonstrate that
      cypermethrin induces alpha-synuclein expression and aggregation while
      cyclosporine A or MnTMPyP rescues from alpha-synuclein over-expression and
      aggregation along with the mitochondrial dysfunction and oxidative damage leading
      to Parkinsonism in rats. 

PMID- 25370935
TI  - PRKCH 1425G/A Polymorphism Predicts Recurrence of Ischemic Stroke in a Chinese
      Population.
AB  - A recent genome-wide association study (GWAS) identified a nonsynonymous SNP
      (1425G/A) in PRKCH which was associated with increased risk of ischemic stroke.
      The purpose of this study was to examine whether this functional polymorphism is
      associated with stroke onset and prognosis in a Chinese population. We genotyped
      PRKCH 1425G/A using Improved Multiple Ligase Detection Reaction in 919 patients
      with ischemic stroke. Analyses of genotype association with onset and prognosis
      outcomes were assessed by the Kaplan-Meier method, the log-rank test, and the Cox
      proportional hazards models. PRKCH 1425G/A was not associated with age of stroke
      onset (P = 0.323). However, this functional polymorphism was significantly
      associated with risk of stroke recurrence in recessive models (hazard ratio [HR]
      = 2.23; 95% confidential interval [CI], 1.06 to 4.68; P = 0.014), and this effect
      was more predominant among smokers (HR = 3.67; 95% CI, 1.47-9.18; P = 0.005).
      Moreover, the variant genotypes of PRKCH 1425G/A are an independent prognostic
      factor for ischemic stroke in the final multivariate Cox regression model. Our
      findings show that PRKCH 1425G/A may be a useful biomarker for predicting the
      recurrence of ischemic stroke.

PMID- 25370936
TI  - The first FDA marketing authorizations of next-generation sequencing technology
      and tests: challenges, solutions and impact for future assays.
AB  - The rapid emergence and clinical translation of novel high-throughput sequencing
      technologies created a need to clarify the regulatory pathway for the evaluation
      and authorization of these unique technologies. Recently, the US FDA authorized
      for marketing four next generation sequencing (NGS)-based diagnostic devices
      which consisted of two heritable disease-specific assays, library preparation
      reagents and a NGS platform that are intended for human germline targeted
      sequencing from whole blood. These first authorizations can serve as a case study
      in how different types of NGS-based technology are reviewed by the FDA. In this
      manuscript we describe challenges associated with the evaluation of these novel
      technologies and provide an overview of what was reviewed. Besides making
      validated NGS-based devices available for in vitro diagnostic use, these first
      authorizations create a regulatory path for similar future instruments and
      assays. 

PMID- 25370937
TI  - Passages 2015.

PMID- 25370938
TI  - TfOH-catalyzed synthesis of 3-aryl isoindolinones via a tandem reaction.
AB  - A convenient metal-free method for the synthesis of 3-aryl isoindolinones via
      TfOH catalyzed aromatic C-H functionalization of electron-rich arenes with 2
      formylbenzonitriles is developed. This process provided a new efficient strategy
      for the synthesis of isoindolinone derivatives in good to high yields and
      regioselectivities by forming two bonds. 

PMID- 25370939
TI  - Hypothalamic obesity.
AB  - Hypothalamic obesity represents a rare diagnosis applicable to only a small
      subset of obese patients. It is important to identify, diagnose, and treat these
      patients. This article reviews the physiology of the hypothalamus, focusing on
      its role in regulation of hunger, feeding, and metabolism. The causes of
      hypothalamic obesity are discussed including genetic, anatomic, and iatrogenic
      etiologies. The complex hormonal environment leading to obesity is explored for
      each etiology and treatment strategies are discussed. Reproductive consequences
      are also reviewed. 

PMID- 25370940
TI  - Ecomorphological variation in male and female wall lizards and the macroevolution
      of sexual dimorphism in relation to habitat use.
AB  - Understanding how phenotypic diversity evolves is a major interest of
      evolutionary biology. Habitat use is an important factor in the evolution of
      phenotypic diversity of many animal species. Interestingly, male and female
      phenotypes have been frequently shown to respond differently to environmental
      variation. At the macroevolutionary level, this difference between the sexes is
      frequently analysed using phylogenetic comparative tools to assess variation in
      sexual dimorphism (SD) across taxa in relation to habitat. A shortcoming of such
      analyses is that they evaluate the degree of dimorphism itself and therefore they
      do not provide access to the evolutionary trajectories of each sex. As such, the
      relative contribution of male and female phenotypes on macroevolutionary patterns
      of sexual dimorphism cannot be directly assessed. Here, we investigate how
      habitat use shapes phenotypic diversity in wall lizards using phylogenetic
      comparative tools to simultaneously assess the tempo and mode of evolution in
      males, females and the degree of sexual dimorphism. We find that both sexes have
      globally diversified under similar, but not identical, processes, where habitat
      use seems to drive macroevolutionary variation in head shape, but not in body
      size or relative limb length. However, we also observe small differences in the
      evolutionary dynamics of male and female phenotypes that have a marked impact on
      macroevolutionary patterns of SD, with important implications for our
      interpretation of what drives phenotypic diversification within and between the
      sexes. 

PMID- 25370941
TI  - Dual photo- and pH-responsive supramolecular nanocarriers based on water-soluble
      pillar[6]arene and different azobenzene derivatives for intracellular anticancer
      drug delivery.
AB  - Two novel types of supramolecular nanocarriers fabricated by the amphiphilic host
      guest inclusion complex formed from water-soluble pillar[6]arene (WP6) and
      azobenzene derivatives G1 or G2 have been developed, in which G1 is structurally
      similar to G2 but has an extra phenoxy group in its hydrophobic region.
      Supramolecular micelles can be initially formed by WP6 with G1, which gradually
      transform into layered structures with liquid-crystalline properties, whereas
      stable supramolecular vesicles are obtained from WP6 and G2, which exhibit dual
      photo- and pH-responsiveness. Notably, the resulting WP6?G2 vesicles can
      efficiently encapsulate anticancer drug mitoxantrone (MTZ) to achieve MTZ-loaded
      vesicles, which maintain good stability in a simulated normal physiological
      environment, whereas in an acid environment similar to that of tumor cells or
      with external UV irradiation, the encapsulated drug is promptly released. More
      importantly, cytotoxicity assay indicates that such vesicles have good
      biocompatibility and the MTZ-loaded vesicles exhibit comparable anticancer
      activity to free MTZ, especially with additional UV stimulus, whereas its
      cytotoxicity for normal cells was remarkably reduced. Flow cytometric analysis
      further confirms that the cancer cell death caused by MTZ-loaded vesicles is
      associated with apoptosis. Therefore, the dual pH- and UV-responsive
      supramolecular vesicles are a potential platform for controlled release and
      targeted anticancer drug delivery. 

PMID- 25370942
TI  - Autocatalytic growth of ZnO nanorods from flat Au(111)-supported ZnO films.
AB  - Physical vapour deposition of ZnO on an Au(111) support has been investigated as
      a function of the oxygen chemical potential by means of scanning tunnelling
      microscopy and luminescence spectroscopy. Whereas a layer-by-layer growth of ZnO
      is revealed in oxygen excess, formation of oxide nanorods with large height-to
      diameter ratio prevails at lower oxygen chemical potentials. We ascribe the
      formation of 3D nanostructures in the latter case to traces of Au atoms on the
      surface that promote trapping and dissociation of the incoming oxygen molecules.
      The Au residuals, acting as catalyst for the oxide formation, are indeed found on
      top of the ZnO nanorods. 

PMID- 25370943
TI  - Hepatocellular carcinomas promote tumor-associated macrophage M2-polarization via
      increased B7-H3 expression.
AB  - B7 family members are aberrantly expressed on the human hepatocellular carcinoma
      (HCC) cell surface, and induce local and systemic immunosuppression. Tumor
      associated macrophages (TAMs) are a significant immune cell subpopulation in HCC
      and may be induced to express co-inhibitory molecules including B7 homologue 3
      (B7-H3). In the present study, 79.3% of the HCC tissue samples showed high
      expression of B7-H3 which was positively correlated with the number of TAMs in
      the evaluated cancer tissues. Furthermore, high levels of TAMs or B7-H3 were
      associated with a shorter survival time of the HCC patients. In vitro, B7-H3
      expression was upregulated at both the mRNA and protein levels in phorbol 12
      myristate 13-acetate (PMA)-induced THP-1 cells cocultured with HepG2 cells in a
      Transwell system. In addition, B7-H3 promoted PMA-induced THP-1 cells to
      differentiate into the M2 phenotype, with evidence of increases in arginase 1
      (Arg1), vascular endothelial cell growth factor (VEGF) and macrophage-derived
      chemokine (CCL22) mRNA following coculture with HepG2 cells. However, this
      phenomenon was abrogated through knockdown of B7-H3 by RNA interference or by
      blocking the signal transducer and activator of trans-cription 3 (STAT3)
      signaling pathway. Overall, these results suggest that the B7-H3-mediated STAT3
      signaling pathway is an important mechanism for inducing M2-type polarization of
      TAMs, which accelerates HCC development. Our findings may support the development
      of novel therapeutic strategies for HCC patients through the skewing of the TAM
      phenotype by targeting the B7-H3 signaling pathway.

PMID- 25370945
TI  - Effect of immunosuppression on the human mesangial cell cycle.
AB  - The present study investigated the effects of immunosuppressive agents
      [tacrolimus (Tac), cyclosporine A (CsA), mycophenolic acid (MMF) and
      methylprednisone (MP)] on the proliferation, cell cycle progression and apoptotic
      rate of human mesangial cells. Cultured human mesangial cells were treated with
      several concentrations of the immunosuppressive agents for 24, 48 or 72 h. Cell
      cycle progression, proliferation and apoptosis were analyzed using an MTT assay
      and flow cytometry. Tac and CsA significantly inhibited the proliferation of
      human mesangial cells in a dose- and time-dependent manner. Cell cycle analysis
      revealed that Tac and CsA arrested mesangial cells in the G0/G1 phase, preventing
      them from entering S phase. Similarly, MP inhibited human mesangial cell growth
      by causing cell cycle arrest in G0/G1 phase. MMF also inhibited mesangial cell
      proliferation, but accomplished this by preventing progression from S phase to
      the G2/M phase. The combination of MP and MMF synergistically inhibited mesangial
      cell proliferation. Tac, CsA, MP and MMF inhibited proliferation of human
      mesangial cells by blocking progression of the cell cycle. In conclusion, these
      agents, sequentially or in combination, may be used to effectively treat
      mesangial proliferative glomerular disease. 

PMID- 25370944
TI  - Circadian rhythms of hydraulic conductance and growth are enhanced by drought and
      improve plant performance.
AB  - Circadian rhythms enable plants to anticipate daily environmental variations,
      resulting in growth oscillations under continuous light. Because plants daily
      transpire up to 200% of their water content, their water status oscillates from
      favourable during the night to unfavourable during the day. We show that rhythmic
      leaf growth under continuous light is observed in plants that experience large
      alternations of water status during an entrainment period, but is considerably
      buffered otherwise. Measurements and computer simulations show that this is due
      to oscillations of plant hydraulic conductance and plasma membrane aquaporin
      messenger RNA abundance in roots during continuous light. A simulation model
      suggests that circadian oscillations of root hydraulic conductance contribute to
      acclimation to water stress by increasing root water uptake, thereby favouring
      growth and photosynthesis. They have a negative effect in favourable hydraulic
      conditions. Climate-driven control of root hydraulic conductance therefore
      improves plant performances in both stressed and non-stressed conditions. 

PMID- 25370946
TI  - Re-emergence of circulatory foot-and-mouth disease virus serotypes Asia1 in
      Bangladesh and VP1 protein heterogeneity with vaccine strain IND 63/72.
AB  - Foot-and-mouth disease virus (FMDV) serotypes O, A and Asia1 are responsible for
      significant number of disease outbreaks in Bangladesh; however serotype Asia1 has
      not been reported in circulation since 1996. The present investigation reports
      the detection of serotype FMDV Asia1 from local farms in 2012 and 2013 outbreaks.
      The farms were located in Jessore and Gazipur districts, and one of these farms
      was under vaccine control programme. Phylogenetic analysis of the complete VP1
      gene revealed that FMDV Asia1 is under genetic lineage C having close similarity
      to the Asia1 sequences of Indian origin. The circulatory genotype Asia1 showed
      VP1 protein sequence heterogeneity of eight amino acid substitutions within the G
      H loop with the vaccine strain [IND 63/72 (AY304994)] used in vaccination
      programme. ELISA assay revealed that, of seven, only one local field serum sample
      (cattle vaccinated 38 days earlier) was positive at a titre level of >2.4 (log10)
      but failed to protect the cattle from infection occurred by the virus. This
      investigation focused that the eight amino acid substitution in VP1 protein at G
      H loop of the locally circulated FMDV serotype Asia1 strain may be a reason for
      current vaccination failure.

PMID- 25370947
TI  - [Acute treatment of hypertension in intracerebral haemorrhage].
AB  - Thus far no effective treatment for an intracerebral haemorrhage has been
      available. A randomized clinical trial recently showed that treatment of
      hypertension in the acute phase of spontaneous intracerebral haemorrhage with a
      target systolic blood pressure of 140 mmHg is safe and improves prognosis. The
      effect of blood pressure reducing therapy was small and not statistically
      significant for the primary outcome (mortality or severe morbidity). Moreover,
      this effect was shown in one trial only. Therefore the clinical relevance of
      these study results remains debatable. Considering all available arguments, in
      patients with a systolic blood pressure >150 mmHg in the first 6 hours after
      spontaneous intracerebral haemorrhage the Dutch Neurovascular Working Group
      recommends lowering the blood pressure to a target systolic level of 140 mmHg
      within 1 hour and maintaining this target level for 1 week. When this strategy is
      not chosen, we recommend that a systolic blood pressure >180 mmHg should be
      treated anyway, with a target level of 160 mmHg.

PMID- 25370948
TI  - [Take the time: primary healthcare for people with intellectual disabilities].
AB  - People with intellectual disabilities (ID) have a higher prevalence of health
      problems than the general population and their health needs are often
      unrecognized and unmet. In this article we present three cases of patients with
      ID to illustrate some specific problems. A 22-year-old man, severely
      intellectually disabled, presented with an unsteady gait. He had recently been
      diagnosed with Cohen Syndrome. Since he was unable to express himself, it took
      some time to discover that he had additional symptoms, e.g. frequent infections.
      Eventually, all his complaints fit with his syndrome. A 54-year-old woman,
      severely to moderately intellectually disabled, presented with new behaviour,
      i.e. loss of appetite, weakness in her legs and excessive thirst. Although she
      was able to speak, she was unable to explain what was wrong with her. Since we
      were aware of the etiology of her disability, Prader Willi syndrome, we were more
      aware of the possibility of diabetes mellitus. A 56-year-old man, mildly
      intellectually disabled, presented with hearing voices for which he received
      antipsychotic medication. After a conversation in simple language, we discovered
      that he heard humming sounds rather than voices. He was ultimately diagnosed with
      tinnitus rather than psychosis. It takes time to discover the health issues that
      affect patients with ID. This is due to communication problems, the inability to
      understand bodily functions, symptoms and diseases, multi-morbidity, the atypical
      presentation of disease at times and the different prevalence rates for certain
      diseases when compared with the general population.

PMID- 25370949
TI  - [Sentinel lymph node procedure in melanoma patients: a staging procedure, not a
      therapy].
AB  - The definitive results of the MSLT-1 study in melanoma patients were published
      recently. The sentinel lymph node (SLN) procedure shows no survival benefit
      compared with observation. The authors reported, however, that there was a
      survival benefit with "biopsy management" of patients. This statement is based on
      subgroup analyses that we find to be incorrect for three reasons: (a) patients
      with a false negative SLN were incorrectly left out of consideration; (b)
      accelerated failure time latent subgroup analysis is an unproven statistical
      hypothesis, which was developed on interim data from the MSLT-1 study, and
      therefore cannot be used as validation; (c) there is a significant difference in
      terms of the percentage of patients with affected lymph nodes between the SLN
      group and the observation group. This excess of "prognostic false positive"
      patients would have incorrectly falsely improved the survival of the SLN group.
      We concluded that the SLN procedure does not give a survival benefit and that its
      role in melanoma patients should be for staging purposes and not for therapeutic
      purposes. 

PMID- 25370951
TI  - [Sentinel lymph node biopsy necessary in melanoma patients].
AB  - Sentinel lymph node biopsy provides melanoma patients with important prognostic
      information and improves staging and regional tumour control, while the morbidity
      is limited and the subsequent quality of life is good. The most important result
      of the only randomised study is the improved ten-year melanoma-specific survival
      in node-positive patients with an intermediate thickness melanoma. We recommend
      sentinel lymph node biopsy as a standard diagnostic procedure for these patients.
      Sentinel lymph node biopsy can be considered in patients with a thinner or
      thicker melanoma. 

PMID- 25370952
TI  - [Varicoses: should invasive treatment be standard?].
AB  - The new Dutch multidisciplinary guideline for diagnosis and treatment of venous
      pathology deals with diagnosis and treatment of varicosis, new surgical
      techniques in obstruction or insufficiency of the deep venous system, crural
      ulcers and compression therapy with hosiery or bandages. It also describes
      classical and new techniques for surgery and endovascular obliteration of
      varicose veins and evidence based criteria for choosing the optimal therapeutic
      strategy. Although the working party puts much emphasis on new invasive therapies
      it neglects to describe the results of conservative therapy such as therapeutic
      elastic stockings and lifestyle advice including weight loss, exercise and
      avoiding standing in upright position for long periods. The general advice to
      choose invasive therapy above conservative therapy except where the result of
      previous invasive therapy has been insufficient or where invasive therapy is not
      an option, seems somewhat over the top. Modern elastic stockings are more
      acceptable as they look good, are transparent and have all kinds of elegant
      extras and the modern fabrics are comfortable for the wearer. Class I compression
      stockings have been shown to be effective in uncomplicated cases and are easier
      to handle than class II, especially for the elderly. 

PMID- 25370953
TI  - Effect of acotiamide on gastric emptying in healthy adult humans.
AB  - BACKGROUND: Acotiamide is a first-in-class drug that is used to treat functional
      dyspepsia (FD). It is considered that acotiamide acts as an antagonist on
      muscarinic autoreceptors in the enteric nervous system and inhibits
      acetylcholinesterase activity. We examined the effect of acotiamide on gastric
      emptying in healthy adult humans. MATERIALS AND METHODS: Twelve healthy adult
      males were enrolled in this double-blind crossover study. Acotiamide or placebo
      was administered orally in the 12 subjects 30 min before ingestion of a
      nutritional liquid meal (400 Kcal/400 mL). Six of the 12 participants took 100 mg
      of acotiamide or placebo, and six of the 12 participants took 300 mg of
      acotiamide or placebo in a double-blind crossover fashion. All subjects underwent
      measurement of gastric emptying by the (13) C breath test. RESULTS: After the
      meal with placebo was ingested, the %dose/h curve ascended. The %dose/h curve
      after a meal with 100 or 300 mg of acotiamide ascended in an identical manner
      compared with the results with placebo. No significant differences were observed
      at any studied time point, and there were no significant changes in gastric
      emptying parameters (gastric emptying coefficient, t-1/2ex and t-lag ex).
      CONCLUSIONS: A single administration of 100 or 300 mg of acotiamide did not
      affect gastric emptying after a liquid meal in healthy adult humans. Acotiamide
      has profound effects on restoring delayed gastric emptying and impaired
      accommodation in patients with FD but may have no effect on gastric emptying in
      healthy subjects. Such pharmacological actions have not been observed in previous
      gastroprokinetic studies.

PMID- 25370954
TI  - CGRP receptor blockade by MK-8825 alleviates allodynia in infraorbital nerve
      ligated rats.
AB  - BACKGROUND: Previous data showed that, in rats, anti-migraine drugs (triptans,
      olcegepant) significantly reduced mechanical allodynia induced by infraorbital
      nerve (ION) ligation but not that evoked by sciatic nerve (SN) ligation. Whether
      this also occurs with MK-8825, a novel anti-migraine drug also acting through
      CGRP receptor blockade (but chemically unrelated to olcegepant) was tested in the
      present study, which also investigated possible anti-neuroinflammatory effects of
      this drug. METHODS: Adult male Sprague-Dawley rats underwent unilateral chronic
      constriction injury (CCI) to either the ION or the SN, and mechanical allodynia
      was assessed 2 weeks later within the ipsilateral vibrissae territory or hindpaw,
      respectively. Transcripts of neuroinflammatory markers were quantified by real
      time quantitative RT-PCR in ipsilateral trigeminal ganglion and spinal trigeminal
      nucleus in CCI-ION rats. RESULTS: Acute as well as repeated (for 4 days)
      administration of MK-8825 (30-100 mg/kg, i.p.) significantly reduced CCI-ION
      induced mechanical allodynia but was ineffective in CCI-SN rats. CCI-ION was
      associated with marked up-regulation of neuronal and glial inflammatory markers
      (ATF3, IL6, iNOS, COX2) in ipsilateral trigeminal ganglion but not spinal
      trigeminal nucleus. MK-8825-induced inhibition of iNOS mRNA up-regulation
      probably underlay its anti-allodynic effect because pharmacological blockade of
      iNOS by AMT (6 mg/kg, s.c.) mimicked this effect. CONCLUSIONS: These data further
      support the idea that CGRP receptor blockade might be a valuable approach to
      alleviate trigeminal, but not spinal, neuropathic pain through, at least partly,
      an inhibitory effect on neuropathic pain-associated increase in NO production in
      trigeminal ganglion.

PMID- 25370955
TI  - Development and microwave analysis of slot antennas for localized hyperthermia
      treatment of hepatocellular liver tumor.
AB  - Slot antennas are often considered as a suitable choice for microwave ablation
      due to design simplicity, low cost to manufacture and a highly confined
      temperature profile. In this paper, an iterative coupled thermal/microwave
      numerical formulation is presented to analyze and develop miniature slot antenna
      geometries for localized liver cancer treatment. The thermal solver determines
      the specific absorption rate (SAR) as a pre-processing step to determine the
      temperature distribution profile within malignant tissues. The microwave solver
      uses this computed thermal solution together with related boundary/sub-domain
      settings to determine complex propagation wave number as an Eigen value. The
      desired microwave response in terms of insertion loss <0.1 dB, VSWR 1:1.1, and
      return loss less than -22 dB was achieved at 2.45 GHz. The simulated results
      agree well with the measured response. 

PMID- 25370956
TI  - CD8+ T cell profiles in patients with rheumatoid arthritis and their relationship
      to disease activity.
AB  - OBJECTIVE: CD8+ T cells are abundant in rheumatoid arthritis (RA). However, their
      role in disease pathogenesis is poorly defined. This study was undertaken to
      investigate the relationship between disease activity and CD8+ T cell phenotypes,
      production of cytokines, and production of cytotoxic molecules in the peripheral
      blood (PB) and synovial fluid (SF) of patients with RA. METHODS: CD8+ T cell
      phenotypes were determined in 96 patients with RA (44 with disease in remission,
      34 with active disease, 18 with low disease activity) and in 64 sex- and age
      matched healthy controls. Ten paired PB and SF samples from patients with active
      RA were analyzed. The expression of surface markers, cytokines, and proteolytic
      enzymes in CD8+ T cells was evaluated using flow cytometry. RESULTS: PB CD8+ T
      cells from RA patients with active disease exhibited an effector (CD27-CD62L-)
      phenotype (P = 0.005), with elevated expression of proinflammatory cytokines
      (tumor necrosis factor alpha [TNFalpha], interferon-gamma [IFNgamma], interleukin
      6 [IL-6], IL-17A) when compared to healthy controls. In a state of remission, the
      same phenotype observed in patients with active disease persisted, including a
      significant increase in the frequency of CD69 (P < 0.001), but lower cytokine
      production was observed. SF CD8+ T cells from RA patients expressed more robust
      effector memory (CD27+CD62L-) and activated (CD69+) profiles compared to the T
      cell subsets in paired PB samples. Production of cytokines (IL-6, IL-17A, and
      IFNgamma) by CD8+ T cells from RA PB was positively correlated within individual
      donors. Moreover, production of cytokines (TNFalpha, IFNgamma, and IL-17A) by
      CD8+ T cells from RA PB positively correlated with the Disease Activity Score in
      28 joints. CONCLUSION: The activation status and proinflammatory potential of
      CD8+ T cell subsets observed in the RA patients in this study strongly suggest
      that a phenotype of local and systemic cytotoxic effector T cells plays a role in
      this disease.

PMID- 25370957
TI  - Psychometric properties of two questionnaires in the context of total wrist
      arthroplasty.
AB  - INTRODUCTION: Patient-rated outcome measures are frequently used to assess the
      results of total wrist arthroplasty, but their psychometric properties have not
      yet been evaluated in this group of patients. The purpose of our study was to
      assess the psychometric properties of the Danish Quick Disabilites of Arm
      Shoulder and Hand (QuickDASH) and Patient-rated Wrist Evaluation questionnaires
      in patients with total wrist arthroplasty. METHODS: In a prospective cohort of
      102 cases, we evaluated the QuickDASH. Furthermore, in a cross-sectional study
      and a test-retest on a subgroup of the patients, we evaluated the Patient-rated
      Wrist Evaluation. RESULTS: Internal consistency and reproducibility were very
      high (Cronbach's alpha 0.96/0.97; Spearman's rho 0.90/ 0.91; intraclass
      coefficient 0.91/0.92), and there were no floor or ceiling effects. The
      responsiveness of the QuickDASH was high (standardised response mean 1.06 and
      effect size 1.07). The construct validity of both scales was confirmed by three a
      priori formulated hypotheses: a moderate, negative correlation of scores with
      grip-strength; a moderate, positive correlation with pain and a very weak or no
      correlation with mobility. Rheumatoid patients scored significantly higher on the
      QuickDASH than other patients did. The scores of both questionnaires were very
      closely related. CONCLUSION: Both questionnaires are valid and equivalent for use
      in patients with total wrist arthroplasty. FUNDING: This research received no
      specific grant from any funding agency in the public, commercial, or not-for
      profit sectors. TRIAL REGISTRATION: not relevant.

PMID- 25370958
TI  - Bone and vitamin D status in patients with anorexia nervosa.
AB  - INTRODUCTION: The aim of the present study was to investigate bone status and
      biological mechanisms involved in the negative impact of anorexia nervosa (AN) on
      osteogenesis. METHODS: A total of 30 AN patients from Aalborg University Hospital
      who underwent bone scans were included in a cross-sectional study. Biochemical
      data, bone scans (dual-energy X-ray absorptiometry (DXA)) as well as general
      health and medical information had been collected during the 2009-2011 period and
      stored via local and national clinical databases in Denmark, and from these
      databases we identified all patients with an AN diagnosis who underwent bone
      scans. RESULTS: AN patients had a mean Z-score of -1.5 to -1.6 in lumbar spine
      and total hip, respectively. The hip Z-score decreased with duration of disease,
      and a positive correlation was seen between serum 25-hydroxy-vitamin D level and
      spine Z-score but not hip Z-score. Bone mineral density did not seem to change
      with time since diagnosis. Additionally, a negative correlation between serum 25
      hydroxy-vitamin D levels and serum total alkaline phosphatase levels was found. A
      serum 25-hydroxy-vitamin D level below 50 nmol/l was associated with increased
      alkaline phosphatase levels. CONCLUSION: Rather than clinical measures including
      BMI and biochemical measures disease duration was the main predictor of bone
      status. This implies that long-term disease should be a main factor in selecting
      patients for referral to DXA. Moreover, results from this study indicate normal
      osteoblastic response to malnutrition. FUNDING: not relevant. TRIAL REGISTRATION:
      The present study was not registered due to its register-based design. However,
      the study was approved by the Danish Data Protection Agency.

PMID- 25370959
TI  - Abdominal binders may reduce pain and improve physical function after major
      abdominal surgery - a systematic review.
AB  - INTRODUCTION: Evidence for the effect of post-operative abdominal binders on post
      operative pain, seroma formation, physical function, pulmonary function and
      increased intra-abdominal pressure among patients after surgery remains largely
      un-investigated. METHODS: A systematic review was conducted. The PubMed, EMBASE
      and Cochrane databases were searched for studies on the use of abdominal binders
      after abdominal surgery or abdominoplasty. All types of clinical studies were
      included. Two independent assessors evaluated the scientific quality of the
      studies. The primary outcomes were pain, seroma formation and physical function.
      RESULTS: A total of 50 publications were identified; 42 publications were
      excluded leaving eight publications counting a total of 578 patients for
      analysis. Generally, the scientific quality of the studies was poor. Use of
      abdominal binder revealed a non-significant tendency to reduce seroma formation
      after laparoscopic ventral herniotomy and a non-significant reduction in pain.
      Physical function was improved, whereas evidence supports a beneficial effect on
      psychological distress after open abdominal surgery. Evidence also supports that
      intra-abdominal pressure increases with the use of abdominal binders. Reduction
      of pulmonary function during use of abdominal binders has not been revealed.
      CONCLUSION: Abdominal binders reduce post-operative psychological distress, but
      their effect on post-operative pain after laparotomy and seroma formation after
      ventral hernia repair remains unclear. Due to the sparse evidence and poor
      quality of the literature, solid conclusions may be difficult to make, and
      procedure-specific, high-quality randomised clinical trials are warranted.

PMID- 25370960
TI  - A novel FBN1 variant in a large Marfan family with high penetrance of aortic
      dissection or rupture.
AB  - INTRODUCTION: Marfan syndrome is an autosomal, dominantly inherited disorder of
      the connective tissue. We report the clinical data and results of a genetic
      analysis of a large Danish Marfan family. METHODS: Sanger sequencing of FBN1 was
      initially performed on genomic DNA from the index patient. Subsequently, four
      affected family members and three non-affected family members were tested for the
      variant identified in the index patient. RESULTS: A novel variant (c.701G>T) in
      the FBN1 segregated with Marfan features in the family. CONCLUSION: In the
      majority of the family members, this novel variant seems to cause a uniform and
      very detrimental set of disease characteristics including fatal aortic
      dissection. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 25370961
TI  - Gastrointestinal bleedings during therapy with new oral anticoagulants are rarely
      reported.
AB  - INTRODUCTION: Post-marketing surveillance of drugs relies on spontaneous
      reporting of adverse drug events to the Danish Health and Medicines Authority. A
      number of new oral anticoagulants (NOAC) have recently been marketed in Denmark.
      The purpose of this study was to evaluate the reporting of serious adverse drug
      events in patients treated with a NOAC and admitted for gastrointestinal
      bleeding. METHODS: This study is based on an electronic free text search in
      patient records and a search in the electronic medication records of all patients
      admitted to the Department of Gastroenterology, Surgical Section, Hvidovre
      Hospital, during a one-year-period. Patients in treatment with NOAC and admitted
      for gastrointestinal bleeding were identified. Relevant patients were cross
      checked for a reported adverse drug event in the Danish Health and Medi-cines
      Authority's database on adverse medical events. RESULTS: A total of 20 patients
      were acutely admitted for gastrointestinal bleeding while in treatment with a
      NOAC, an adverse medical event was reported for one of these patients (5%; 95%
      confidence interval: 0-25%). CONCLUSION: Serious adverse events in patients
      treated with NOAC are underreported which questions the current effectiveness of
      post-marketing surveillance of adverse drug effects. FUNDING: not relevant. TRIAL
      REGISTRATION: The study was registered with clin-icaltrials.gov (NCT02107651).

PMID- 25370963
TI  - Prophylactic antibiotics reduce sepsis after biopsy of the prostate.
AB  - INTRODUCTION: Prostate cancer is the most common form of cancer in Danish men,
      and the incidence is rising. The diag-nosis is made by transrectal prostate
      biopsy guided by ultrasound. This procedure has several complications, the most
      severe being sepsis. In our department, this is sought prevented by administering
      the prophylactic antibiotics metronidazol and ciprofloxacin. This study examined
      the rate of sepsis in patients who had the procedure performed at our department.
      METHODS: The electronic patient records of all patients who had transrectal
      ultrasound of the prostate with biopsies performed at the Department of Urology
      at Naestved Hospital in the period from 1 May 2009 to 31 May 2011 were examined,
      and all admissions to our department (or any department in the same region) due
      to sepsis within two weeks of the procedure were registered. RESULTS: A total of
      438 patients had the procedure performed, some multiple times, which resulted in
      a total of 511 procedures. In all, four patients were later admitted due to
      sepsis, corresponding to 0.91%. Three of the patients had positive blood and
      urine cultures in which Escherichia coli resistant to ciprofloxacin were found,
      the last had been prescribed antibiotics by a general practitioner the previous
      day, and no bacteria could be cultured. CONCLUSION: The frequency of sepsis after
      transrectal needle biopsies from the prostate at our department was found to be
      below 1% in this study, which is comparable to international findings. Most of
      the cases of sepsis were related to ciprofloxacin-resistant bacteria. Further
      randomised studies are needed to investigate the ideal prophylactic regime.
      FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 25370962
TI  - Reorganisation of acute referral to an emergency department resulted in fewer
      admissions for chronic obstructive pulmonary disease but in higher rates of non
      invasive ventilation.
AB  - INTRODUCTION: We performed an audit on all admissions with chronic obstructive
      pulmonary disease (COPD) in ex-acerbation to the Department of Emergency
      Medicine, Odense University Hospital (DEM) in the second half of 2012 to evaluate
      if an organisational change had altered visitation, treatment, initiation of non
      invasive ventilation (NIV) and monitoring. We chose not to include the entire
      year to avoid data influenced by organisational start-up difficulties. The
      hypothesis was that NIV was initiated according to guidelines to the same extent
      as prior to the implementation of DEM. METHODS: Data from medical records were
      retrieved from two COPD cohorts: 1) all patients admitted to DEM between 1 July
      and 31 December 2012 and 2) all patients admitted to the Medical Emergency Ward,
      Odense University Hospital (MEW) in 2010. RESULTS: There were 300 eligible
      admissions comprising 236 unique patients in DEM in the second half of 2012
      compared with 393 admissions in MEW in the second half of 2010, a 24% reduction.
      The groups were similar in gender and age, but patients admitted in 2012 had
      higher registered co-morbidity rates, but no significant difference in lung
      function values. NIV was indicated in 91 admissions (30%) and initiated in 58
      admissions (19.3%) in 2012. By comparison NIV was indicated in 193 admissions
      (24%) and initiated in 151 admissions (18.8%) in 2010. CONCLUSION: There was a
      statistically significant increase in NIV indication without initiation of
      treatment in 2012 (28 admissions; 9.3%) compared with 2010 (36 admissions; 4.5%),
      but no referrals to the intensive care unit or deaths were registered during the
      hospitalisation in either of the groups, but one patient died within 30 days
      after admission from the DEM. FUNDING: This project was funded by an Odense
      University Hospital research grant. TRIAL REGISTRATION: The study was approved by
      the Danish Data Protection Agency (record no. 2011-41-6459).

PMID- 25370964
TI  - Diagnostic performance of quantitative fluorescence PCR analysis in high-risk
      pregnancies after combined first-trimester screening.
AB  - INTRODUCTION: We aimed to determine the diagnostic efficiency of quantitative
      fluorescence polymerase chain reaction (QF-PCR) in a clinical setting where most
      of the analyses are performed on chorion villus samples from high-risk
      pregnancies as determined by combined first-trimester screening. METHODS: A
      retrospective study on QF-PCR data from all pregnancies in the Central and North
      Denmark Regions over a four-year period (n = 2,550) with invasive prenatal
      testing carried out due to a high risk of carrying a foetus with Down's syndrome.
      Results of QF-PCR were compared with those obtained by karyotyping. Other
      supplementary data were obtained from the Danish Foetal Medicine Database and the
      Danish Cytogenetic Central Register. RESULTS: QF-PCR for common aneuploidies is
      fast, has a low failure rate, and is associated with high positive and negative
      predictive values (PPV, NPV) (> 99.8%) for all analysed abnormal karyotypes
      except for mosaicism for trisomy 13 (PPV = 20%) and sex chromosome mosaic cases
      (PPV = 40%; NPV = 99.7%)). In 25 (1%) cases, clinically significant chromosome
      abnormalities other than chromosomes 13, 18, 21, X, and Y were identified by
      karyotyping. CONCLUSION: QF-PCR is a rapid and accurate diagnostic method to
      detect common aneuploidies in high-risk pregnancies. However, the rapid test
      cannot stand alone as several clinically significant abnormal karyotypes would be
      overlooked. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 25370965
TI  - Social inequality in chronic disease outcomes.
AB  - Socioeconomic differences in morbidity and mortality, particularly across
      educational groups, are widening. Differential exposures to behavioural risk
      factors have been shown to play an important mediating role on the social
      inequality in chronic diseases such as heart disease, cerebrovascular disease,
      chronic obstructive pulmonary disease, and lung cancer. However, much less
      attention has been given to the potential role of interaction, where the same
      level of exposure to a behavioural risk factor has different effect across
      socioeconomic groups, creating subgroups that are more vulnerable than others. In
      this thesis, Paper 1 describes the unique cohort consortium which was established
      by pooling and harmonising prospective data from existing cohort studies in
      Denmark. This consortium generated a large study population with long follow-up
      sufficient to study power demanding questions of mechanisms underlying social
      inequalities in chronic disease outcomes. In Paper 2 on incidence of coronary
      heart disease, smoking and body mass index partially mediated the observed
      educational differences. This result suggested that some of the social inequality
      in coronary heart disease may be enhanced by differential exposure to behavioural
      risk factors (i.e. smoking and obesity). In Paper 3 on incidence of stroke, an
      observed interaction between education and smoking indicated that participants,
      particularly men, with low level of education may be more vulnerable to the
      effect of smoking than those with high level of education in terms of ischemic
      stroke. Finally, Paper 4 revealed that behavioural risk factors, primarily
      smoking, explained a considerable part of the educational differences in cause
      specific mortality. Further, this paper added important knowledge about the
      considerable part of the mediated effect, which could be due to interaction
      between education and smoking. In conclusion, the research in this thesis is a
      practical implementation of contemporary statistical methodology, the additive
      hazards models, in which the potential role of behavioural risk factors can be
      regarded not only as mediation but also as interaction with the effect of
      socioeconomic position on chronic disease outcomes. The results support that two
      central mechanisms, differential exposure and differential vulnerability to
      behavioural risk factors, particularly smoking; have contributed substantially to
      the social inequality in chronic disease outcomes in Denmark. These mechanism are
      not mutually exclusive and should be regarded simultaneously. However, the
      findings could be non-causal associations due to, for instance, psychosocial or
      environmental factors. Nevertheless, research on social inequality in chronic
      disease outcomes should regard not only that the smoking prevalence is higher in
      lower socioeconomic groups (differential exposure), but also that health
      consequences of being a smoker seem to be worse in these subgroups (differential
      vulnerability). 

PMID- 25370966
TI  - The role of T cell potassium channels, KV1.3 and KCa3.1, in the inflammatory
      cascade in ulcerative colitis.
AB  - Ulcerative Colitis (UC) is a chronic inflammatory bowel disease located in the
      mucosa of the large bowel. UC often affects young adults between 15 and 40 years
      of age with no pre-dominant sex. Over time, incidence rates are steadily
      increasing and the cause of the disease remains unknown. Symptoms are general
      discomfort and bloody diarrhea. UC is diagnosed by endoscopic examination of the
      large bowel, where different hallmarks are found. It is of great importance that
      attacks/relapses are treated medically, as flares may cause death due to
      inflammatory destruction of the mucosa and perforation of the colon leading to
      extreme infection of the abdominal cavity. UC often affects the social life of
      the patients, as they feel that they must be in the immediate vicinity of
      toilets. Therefore, many patients prefer to stay at home during active disease.
      For society, UC is a costly disease due to patients reporting in sick and
      expensive medications. When medical treatment fails, UC patients must undergo
      surgery and have their colon removed (colectomy). This PhD project focused on the
      immune system of the body. Specifically, we looked into T cells (the chairmen of
      the immune system) that we believe play an important role in disease activity.
      When T cells are activated in inflammatory diseases, they produce several
      signaling substances (cytokines) that attract and activate the other parts of the
      immune system. T cells regulate their effector functions through calcium
      regulation. Upon activation, calcium is released from intracellular stores, which
      causes calcium channels to be embedded in the cell membrane (CRAC channels). As
      long as the T cells are stimulated, the two potassium channels KV1.3 and KCa3.1
      maintain the driving force for calcium influx, thus keeping the T cells
      activated. Our aims were to investigate whether the two potassium channels KV1.3
      and KCa3.1 were upregulated in mucosal biopsies from patients with active UC and
      whether there were correlations between the expression of the channels and the
      disease severity assessed by endoscopic and histological evaluation. Moreover, we
      used a rat colitis model (dextran sodium sulphate-induced) to examine the effect
      of pharmacological inhibition of KV1.3 and KCa3.1 on inflammation. We found that
      the expression of T cell potassium channel, KV1.3, was increased in active UC and
      a higher expression correlated well with both the endoscopic and the histological
      degree of inflammation. This suggests KV1.3 to be involved in the inflammatory
      process of UC. We did not find an increase of the other potassium channel,
      KCa3.1, at the gene expression level, but the channels were definitely present in
      the infiltrating T cells as examined by immunostaining. Preliminary gene
      expression data showed similar changes of gene expression in biopsies from Crohns
      disease (CD) patients. In addition, we conducted first pilot studies
      investigating whether pharmacological blockade of the channels ameliorates
      colitis in the rat DSS-model. We found a tendency towards less endoscopic
      inflammation in the acute phase (at day 7 and 10). However, at study termination,
      the improvement of inflammation failed to reach a significant level, presumably
      because of insufficient compound absorption from the intestine (based on low
      plasma concentration and previously reported amelioration of colitis by
      inhibiting KCa3.1). Based on these findings in our target identification study,
      it is suggested that both KV1.3 and KCa3.1 play a role in the inflammation of UC
      and possibly of CD and represent new pharmacological targets. 

PMID- 25370967
TI  - Prognostic factors in soft tissue sarcoma.
AB  - Despite major advances in the knowledge of soft tissue sarcoma (STS) during the
      last decades, no significant improvement in survival has been observed. Detailed
      data on the prognosis of STS are crucial in order to identify patients who might
      benefit from more aggressive treatment. Such data can be obtained from properly
      designed databases; however, the validation of data is crucial in order to obtain
      valid, reliable results. Furthermore, the majority of prognostic studies in STS
      have been limited by potential selection bias, low power, and biased estimates
      due to the statistical methods used, e.g., dichotomizing continuous variables,
      censoring competing events, as well as not adjusting for important confounders.
      The overall aim of this thesis was to investigate the prognosis of STS patients
      using data from the Aarhus Sarcoma Registry (ASR), covering western Denmark in
      the period from 1979 to 2008. In study I, we systematically validated data in the
      ASR and evaluated the validity, including completeness of patient registration
      and accuracy of data. In study II, we investigated the prognostic impact of
      patient-, tumor-, and treatment-related factors on local recurrence and disease
      specific mortality. These were analyzed in a competing risk model in which
      continuous variables were included as cubic splines and possible confounders were
      selected based on directed acyclic graphs. In study III, we examined the impact
      of comorbidity on overall and disease-specific mortality. In study IV, we
      compared mortality in patients with abnormal biomarkers to those with normal
      values, assessed the significance of adjusting for comorbidity, as well as
      constructed a prognostic biomarker score. In study V, we described the relative
      mortality, i.e., the mortality in STS patients compared with the mortality in a
      general population, and compared relative and disease-specific estimates. The
      mortality in the general population was determined using an individually age- and
      sex-matched comparison cohort. All five studies were conducted in western Denmark
      within a population of approximately 2.5 million. Individual linkage between the
      ASR and national registries was made possible by the unique Danish civil
      registration number. The National Patient Registry and the LABKA research
      database were used to obtain data on comorbidity and biomarkers. In studies II to
      V we used a time-to-event-analysis approach that included cumulative incidence
      functions as well as crude and confounder adjusted Cox proportional hazard
      regression. In study I, we established that the overall validity of data in the
      ASR, after validation, was satisfactory and that the ASR included 85.3% of
      sarcoma patients from western Denmark between 1979 and 2008. In study II, we
      found a five-year local recurrence and disease-specific mortality of 16% and 24%,
      respectively. We excluded depth as a prognostic factor, and established that age,
      duration of symptoms, tumor size, anatomical and compartmental location, as well
      as radiotherapy were important prognostic factors for disease-specific mortality.
      In study III, we found that the level of comorbidity before or at diagnosis was
      an independent prognostic factor for both overall and disease-specific mortality,
      even after adjustment for age. In study IV, we showed that pretreatment levels of
      albumin, hemoglobin, and neutrophil to lymphocyte ratios were independently
      correlated with disease-specific mortality, and that adjusting for comorbidity
      was significant. In study V, we found five- and ten-year relative mortalities of
      32.8% and 36.0%, respectively. The mortality in patients with low-grade STS was
      not significantly increased compared with the general population. The five- and
      ten-year disease-specific mortalities were underestimated by 3.1 and 1.9
      percentage points compared to the relative mortality, respectively. We showed
      that relative mortality provided an accurate method to differentiate between
      cancer-specific and non-cancer-specific deaths. In conclusion, we showed that the
      ASR is a valid source of population-based data on STS. Improving the statistical
      methods used in prognostic studies of STS is important in order to obtain
      unbiased and reliable results. The level of comorbidity and bio-markers were
      important prognostic factors and should be used to identify high-risk STS
      patients who might benefit from more aggressive treatment. 

PMID- 25370968
TI  - Persistent organochlorine pollutants and human reproductive health.
AB  - The present dissertation focuses on the reproductive health effects in humans
      from four diverse populations, including an Inuit population from Greenland, a
      Swedish population of fishermen and fishermen's wives, and urban populations from
      the cities of Warsaw in Poland and Kharkiv in Ukraine, representing populations
      with considerable variations in organochlorine exposure levels due to differences
      in the consumption of contaminated food items and the period since banning the
      use of the organochlorines selected in the present study. Due to bioaccumulation
      and their long half-lives in humans, these compounds are still ubiquitously
      detected in humans. The study included a total of 2,269 women who provided
      information via detailed questionnaires and 798 men who provided semen samples.
      Time to pregnancy varied between the populations included, whereas semen quality
      was remarkably similar with only minor differences in motility between countries
      and within regions in Greenland. An extensive quality control programme ensured a
      low level of variation between analysers in the evaluation of semen quality
      during semen sample collection. Sperm concentration and morphology were not
      associated with PCB-153 or DDE exposure, but sperm motility was consistently
      associated with PCB-153 exposure across populations. Xeno-estrogen, -androgen and
      dioxin-like activity in serum samples were not consistently associated with semen
      quality measures, indicating that the associations observed with sperm motility
      were not caused via direct effects on these receptors. The sperm chromatin
      structure assay showed a higher level of DNA fragmentation under higher PCB-153
      exposure levels in the European populations, but not in the Greenlandic
      population. Disturbances in the female menstrual cycle were not consistently
      associated with PCB-153 or DDE exposure across the countries, but our results
      suggested a higher probability of ever having a spontaneous abortion among women
      with high PCB-153 or DDE exposure levels. Overall, the results suggest that PCB
      153, but probably not DDE, may affect aspects of male and female reproductive
      functioning in European and Arctic populations at the levels of exposure
      currently experienced in these populations, although the associations observed
      did not seem to be a major cause of reduced human fertility. 

PMID- 25370969
TI  - National consensus on management of peptic ulcer bleeding in Denmark 2014.
AB  - DESCRIPTION: The Danish Society of Gastroenterology and Hepatology have compiled
      a national guideline for the management of peptic ulcer bleeding. Sources of data
      included published studies up to June 2014. Quality of evidence and strength of
      recommendations have been graded. The guideline was approved by the Danish
      Society of Gastroenterology and Hepatology September 4, 2011. The current version
      is revised June 2014. RECOMMENDATIONS: RECOMMENDATIONS emphasize the importance
      of early and efficient resuscitation. Use of a restrictive blood transfusion
      policy is recommended in haemodynamically stable patients without serious
      ischaemic disease. Endoscopy should generally be performed within 24 hours,
      reducing operation rate, rebleeding rate and duration of in-patient stay. When
      serious ulcer bleeding is suspected and blood found in gastric aspirate,
      endoscopy within 12 hours will result in faster discharge and reduced need for
      transfusions. Endoscopic hemostasis remains indicated for high-risk lesions.
      Hemoclips, thermocoagulation, and epinephrine injection are effective in
      achieving endoscopic hemostasis. Use of endoscopic monotherapy with epinephrine
      injection is not recommended. Intravenous high-dose proton pump inhibitor (PPI)
      therapy for 72 hours after successful endoscopic hemostasis is recommended even
      though the evidence is questionable. Although selected patients can be discharged
      promptly after endoscopy, high-risk patients should be hospitalized for at least
      three days after endoscopic hemostasis. Patients with peptic ulcer bleeding who
      require secondary cardiovascular prophylaxis should start receiving
      acetylsalicylic acid (ASA) within 24 hours from primary endoscopy. Patients in
      need of continued treatment with ASA or a nonsteroidal anti-inflammatory drug
      should be put on prophylactic treatment with PPI at standard dosage. The
      combination of 75 mg ASA and PPI should be preferred to monotherapy with
      clopidogrel in patients needing anti-platelet therapy on the basis of indications
      other than coronary stents. Low-risk patients without clinical suspicion of
      peptic ulcer bleeding who have a Glasgow Blatchford score <= 1 can be offered out
      patient care, unless hospital admission is required for other reasons.

PMID- 25370970
TI  - It takes a team.

PMID- 25370972
TI  - Avoiding emergency department visits for COPD, pneumonia, and heart failure: when
      should patients go to the emergency department?
AB  - Patients with pneumonia, chronic obstructive pulmonary disease (COPD), and heart
      failure make frequent visits to the emergency department. Heart failure alone is
      the reason for more than 1 million emergency department visits annually in the
      United States. This article describes strategies home care clinicians can use to
      prevent unnecessary emergency department visits for patients with pneumonia, COPD
      and heart failure. 

PMID- 25370974
TI  - Dogs as pets, visitors, therapists and assistants.
AB  - Dogs can play an integral role in the recovery of patients through companionship,
      animal-assisted therapy, and as assistance dogs. This article will define and
      differentiate these 3 categories and provide resources for home healthcare and
      hospice clinicians who may want to include dogs in the plan of care for select
      patients. 

PMID- 25370975
TI  - Lillian Wald: a pioneer of home healthcare in the United States.
AB  - Lillian Wald, a pivotal figure in nursing history, is known as the mother of
      public health nursing and renowned as a ground-breaking social worker. In
      founding the Henry Street Settlement in 1893, Wald also launched the Visiting
      Nurse Service of New York (VNSNY), today the nation's largest nonprofit home and
      community-based healthcare organization. This article describes Lillian Wald's
      contributions to public health and community nursing. 

PMID- 25370976
TI  - Safety first for a homebound patient with dementia.
AB  - This article is a short case study that describes how a certified geriatric case
      manager coordinated care and provided safe alternatives to institutional care for
      an elderly, community dwelling patient with dementia. 

PMID- 25370978
TI  - How to enjoy the holidays with diabetes.

PMID- 25370977
TI  - Hypertension management guidelines update and research on the importance of blood
      pressure control.
AB  - According to the Centers for Disease Control and Prevention (CDC), more than 65
      million adults in America have hypertension (HTN) and fewer than half of those 65
      million people have their blood pressure (BP) under control. More than 1,000
      deaths occur each day related to HTN and Americans are at an increased risk of
      complications related to uncontrolled BP such as heart failure, stroke,
      myocardial infarction, and kidney disease (). Data from the National Home and
      Hospice Survey, which is conducted by the CDC, indicate that 41% of home care
      patients have HTN (). This research brief column profiles four recently published
      articles on HTN. The first discusses the most recent guidelines for managing HTN,
      which were released in early 2014. The second article describes the success of an
      intensive structured HTN medication management and management protocol. The third
      and fourth briefs describe studies investigating the ongoing risk of HTN
      poststroke. 

PMID- 25370979
TI  - ISMP medication errors.

PMID- 25370980
TI  - Breaches in infection control practices.

PMID- 25370981
TI  - A day in the life of a Veteran Affairs home care case manager.

PMID- 25370982
TI  - Understanding health literacy.

PMID- 25370983
TI  - Accountable care organizations and home care: strategies for success.

PMID- 25370984
TI  - The unspoken epidemic.

PMID- 25370986
TI  - Bifunctional catalysts based on m-phenylene-bridged porphyrin dimer and trimer
      platforms: synthesis of cyclic carbonates from carbon dioxide and epoxides.
AB  - Highly active bifunctional diporphyrin and triporphyrin catalysts were
      synthesized through Stille coupling reactions. As compared with a porphyrin
      monomer, both exhibited improved catalytic activities for the reaction of CO2
      with epoxides to form cyclic carbonates, because of the multiple catalytic sites
      which cooperatively activate the epoxide. Catalytic activities were carefully
      investigated by controlling temperature, reaction time, and catalyst loading, and
      very high turnover number and turnover frequency were obtained: 220 000 and 46
      000 h(-1) , respectively, for the magnesium catalyst, and 310 000 and 40 000 h(
      1) , respectively, for the zinc catalyst. Results obtained with a zinc/free-base
      hybrid diporphyrin catalyst demonstrated that the Br(-) ions on the adjacent
      porphyrin moiety also function as nucleophiles. 

PMID- 25370985
TI  - Needle puncture in rabbit functional spinal units alters rotational biomechanics.
AB  - STUDY DESIGN: An in vitro biomechanical study for rabbit lumbar functional spinal
      units (FSUs) using a robot-based spine testing system. OBJECTIVE: To elucidate
      the effect of annular puncture with a 16 G needle on mechanical properties in
      flexion/extension, axial rotation, and lateral bending. SUMMARY OF BACKGROUND
      DATA: Needle puncture of the intervertebral disk has been shown to alter
      mechanical properties of the disk in compression, torsion, and bending. The
      effect of needle puncture in FSUs, where intact spinal ligaments and facet joints
      may mitigate or amplify these changes in the disk, on spinal motion segment
      stability subject to physiological rotations remains unknown. METHODS: Rabbit
      FSUs were tested using a robot testing system whose force/moment and position
      precision were assessed to demonstrate system capability. Flexibility testing
      methods were developed by load-to-failure testing in flexion/extension, axial
      rotation, and lateral bending. Subsequent testing methods were used to examine a
      16 G needle disk puncture and No. 11 blade disk stab (positive control for
      mechanical disruption). Flexibility testing was used to assess segmental range-of
      motion (degrees), neutral zone stiffness (N m/degrees) and width (degrees and N
      m), and elastic zone stiffness before and after annular injury. RESULTS: The
      robot-based system was capable of performing flexibility testing on FSUs-mean
      precision of force/moment measurements and robot system movements were <3% and
      1%, respectively, of moment-rotation target values. Flexibility moment targets
      were 0.3 N m for flexion and axial rotation and 0.15 N m for extension and
      lateral bending. Needle puncture caused significant (P<0.05) changes only in
      flexion/extension range-of-motion and neutral zone stiffness and width (N m)
      compared with preintervention. No. 11 blade-stab significantly increased range-of
      motion in all motions, decreased neutral zone stiffness and width (N m) in
      flexion/extension, and increased elastic zone stiffness in flexion and lateral
      bending. CONCLUSIONS: These findings suggest that disk puncture and stab can
      destabilize FSUs in primary rotations.

PMID- 25370988
TI  - Papular mucinosis of the breast after radiation therapy.
AB  - Localized papular mucinosis is a type of mucinosis induced by several different
      causes. However, to the best of our knowledge, prior radiation therapy has not
      been reported to be related to papular mucinosis. We present a case of a 47-year
      old woman who had undergone an operation for a breast carcinoma 2 years earlier
      and received local radiotherapy in the affected breast. Currently, she presents
      multiple erythematous papules that are caused by abundant dermal mucin deposits.
      We discuss some potential differential diagnoses. 

PMID- 25370987
TI  - Biological effect of ketamine in urothelial cell lines and global gene expression
      analysis in the bladders of ketamine-injected mice.
AB  - Ketamine is used clinically for anesthesia but is also abused as a recreational
      drug. Previously, it has been established that ketamine-induced bladder
      interstitial cystitis is a common syndrome in ketamine-abusing individuals. As
      the mechanisms underlying ketamine-induced cystitis have yet to be revealed, the
      present study investigated the effect of ketamine on human urothelial cell lines
      and utilized a ketamine-injected mouse model to identify ketamine-induced changes
      in gene expression in mice bladders. In the in vitro bladder cell line assay,
      ketamine induced cytotoxicity in a dose- and time-dependent manner. Ketamine
      arrested the cells in G1 phase and increased the sub-G1 population, and also
      increased the barrier permeability of these cell lines. In the ketamine-injected
      mouse model, ketamine did not change the body weight and bladder histology of the
      animals at the dose of 30 mg/kg/day for 60 days. Global gene expression analysis
      of the animals' bladders following data screening identified ten upregulated
      genes and 36 downregulated genes induced by ketamine. A total of 52% of keratin
      family genes were downregulated, particularly keratin 6a, 13 and 14, which was
      confirmed by polymerase chain reaction analysis. Keratin 14 protein, one of the
      36 ketamine-induced downregulated genes, was also reduced in the ketamine-treated
      mouse bladder, as determined by immunohistochemical analysis. This suggested that
      cytotoxicity and keratin gene downregulation may have a critical role in ketamine
      induced cystitis.

PMID- 25370989
TI  - Changes in the nitric oxide-soluble guanylate cyclase system and natriuretic
      peptide receptor system in placentas of pregnant Dahl salt-sensitive rats.
AB  - AIM: Diminished vasodilator activity during pregnancy, which augments vascular
      responses to vasoconstrictors, is one reason for the onset of pre-eclampsia and
      superimposed pre-eclampsia. It is known that Dahl salt-sensitive (Dahl-S) rats
      develop salt-sensitive hypertension like African-Americans. The present study
      attempted to assess the changes and the interactions of the NOS-NO-sGC-cGMP and
      NP-NPR-cGMP systems in the hypertensive placenta using Dahl-S rats as an animal
      model of superimposed pre-eclampsia. MATERIAL AND METHODS: Pregnant Dahl-S rats
      were fed a high-salt diet to induce the development of hypertension and fetal
      growth restriction. Using these rats, we investigated the regulation of these two
      vasodilatation systems, including the kinetics of cyclic guanosine monophosphate
      (cGMP), soluble guanylate cyclase (sGC), endothelial nitric oxide synthase (NOS),
      cytokine-inducible NOS, natriuretic peptides (NP) (atrial NP, brain NP and C-type
      NP), and NP receptors (NPR) (NPR-A, NPR-B, NPR-C). RESULTS: Dahl-S rats fed a
      high-salt diet exhibited hypertension, fetal growth restriction and thickening of
      the walls in decidual vessels. The placental cGMP level in the rats fed the high
      salt diet was significantly decreased compared with that in controls. The
      expression levels of endothelial NOS and cytokine-inducible NOS mRNA increased
      significantly, while that of sGCalpha2-sunbnit declined significantly. Messenger
      RNA levels of NPR-C, a clearance-type receptor of NP, declined significantly,
      whereas those of NP and their functional receptors NPR-A and NPR-B were
      unchanged. CONCLUSIONS: As Dahl-S rats with excess salt-loading during pregnancy
      exhibited pathological changes similar to those observed in female humans with
      pre-eclampsia/superimposed pre-eclampsia, this rat could be useful as an animal
      model of superimposed pre-eclampsia. In the placentas of hypertensive Dahl-S
      rats, vasodilatation seemed to be disturbed by the deregulation of both the NO
      sGC-cGMP and NP-NPR-cGMP systems.

PMID- 25370992
TI  - By-products resulting from lignocellulose pretreatment and their inhibitory
      effect on fermentations for (bio)chemicals and fuels.
AB  - Lignocellulose might become an important feedstock for the future development of
      the biobased economy. Although up to 75 % of the lignocellulose dry weight
      consists of sugar, it is present in a polymerized state and cannot be used
      directly in most fermentation processes for the production of chemicals and
      fuels. Several methods have been developed to depolymerize the sugars present in
      lignocellulose, making the sugars available for fermentation. In this review, we
      describe five different pretreatment methods and their effect on the sugar and
      non-sugar fraction of lignocellulose. For several pretreatment methods and
      different types of lignocellulosic biomass, an overview is given of by-products
      formed. Most unwanted by-products present after pretreatment are dehydrated sugar
      monomers (furans), degraded lignin polymers (phenols) and small organic acids.
      Qualitative and quantitative effects of these by-products on fermentation
      processes have been studied. We conclude this review by giving an overview of
      techniques and methods to decrease inhibitory effects of unwanted by-products.

PMID- 25370991
TI  - Domestic violence against women in Eastern Sudan.
AB  - BACKGROUND: Violence against women is one of the major public health problems in
      both developed and developing worlds. The aim of this study was to investigate
      the prevalence of current (occurred in one year preceding the survey) domestic
      violence and socio-demographic factors associated with domestic violence against
      women. METHODS: This was a cross sectional household survey (face to face
      interview) conducted in Kassala, eastern Sudan, from 1(st) March to 1(st) June
      2014. Multivariable analyses were performed, Confidence intervals of 95% were
      calculated and P < 0.05 was considered significant. RESULTS: Of the 1009 women,
      33.5% (338) reported current experience of physical violence and, of these 338
      women, 179 (53%) and 159 (47%) reported moderate and severe form of physical
      violence respectively. The prevalence of sexual coercion, psychological violence
      and verbal insult was 17% (172?1009), 30.1% (304?1009) and 47.6% (480?1009)
      respectively. In the majority of cases, violence was experienced as repeated
      acts, ie, more than three times per year. For verbal insult 20.1% (203?480) and
      27.5% (277?480) reported yelling and shouting respectively. Again 251 (24.9%) and
      270 (26.8%) women reported that they experience divorce threat and second
      marriage threat respectively. In logistic regression model, husband's education
      (OR = 1.5; CI = 1.0-2.1; P = 0.015), polygamous marriage (OR = 1.9; CI = 1.3-2.9;
      P = 0.000), and husband's alcohol consumption (OR = 13.9; CI = 7.9-25.4; P
      <0.000) were significantly associated with domestic violence. CONCLUSIONS:
      Domestic violence was found to be highly prevalent in eastern Sudan and strongly
      associated with the educational status, polygamous marriage and husband's alcohol
      consumption. We recommend more research to include men.

PMID- 25370990
TI  - Decomposition of RNA methylome reveals co-methylation patterns induced by latent
      enzymatic regulators of the epitranscriptome.
AB  - Biochemical modifications to mRNA, especially N6-methyladenosine (m6A) and 5
      methylcytosine (m5C), have been recently shown to be associated with crucial
      biological functions. Despite the intriguing advancements, little is known so far
      about the dynamic landscape of RNA methylome across different cell types and how
      the epitranscriptome is regulated at the system level by enzymes, i.e., RNA
      methyltransferases and demethylases. To investigate this issue, a meta-analysis
      of m6A MeRIP-Seq datasets collected from 10 different experimental conditions
      (cell type/tissue or treatment) is performed, and the combinatorial
      epitranscriptome, which consists of 42 758 m6A sites, is extracted and divided
      into 3 clusters, in which the methylation sites are likely to be hyper- or hypo
      methylated simultaneously (or co-methylated), indicating the sharing of a common
      methylation regulator. Four different clustering approaches are used, including K
      means, hierarchical clustering (HC), Bayesian factor regression model (BFRM) and
      nonnegative matrix factorization (NMF) to unveil the co-methylation patterns. To
      validate whether the patterns are corresponding to enzymatic regulators, i.e.,
      RNA methyltransferases or demethylases, the target sites of a known m6A
      regulator, fat mass and obesity-associated protein (FTO), are identified from an
      independent mouse MeRIP-Seq dataset and lifted to human. Our study shows that 3
      out of the 4 clustering approaches used can successfully identify a group of
      methylation sites overlapping with FTO target sites at a significance level of
      0.05 (after multiple hypothesis adjustment), among which, the result of NMF is
      the most significant (p-value 2.81*10(-06)). We defined a new approach evaluating
      the consistency between two clustering results which shows that clustering
      results of different methods are highly correlated strongly indicating the
      existence of co-methylation patterns. Consistent with recent studies, a number of
      cancer and neuronal disease-related bimolecular functions are enriched in the
      identified clusters, which are biological functions that can be regulated at the
      epitranscriptional level, indicating the pharmaceutical prospect of RNA N6
      methyladenosine-related studies. This result successfully reveals the linkage
      between the global RNA co-methylation patterns embedded in the epitranscriptomic
      data under multiple experimental conditions and the latent enzymatic regulators,
      suggesting a promising direction towards a more comprehensive understanding of
      the epitranscriptome.

PMID- 25370993
TI  - Dynamics of biomass composition and growth during recovery of nitrogen-starved
      Chromochloris zofingiensis.
AB  - The effect of nitrogen replenishment on the kinetics of secondary carotenoids,
      triacylglycerol (TAG) and primary cell components was studied in nitrogen-starved
      Chromochloris zofingiensis (Chlorophyta), an oleaginous and carotenogenic
      microalga. Nitrogen resupplied after a period of starvation was initially
      consumed at a more than four times higher rate than in an equivalent nitrogen
      replete culture. Simultaneously, chlorophylls, primary carotenoids, polar
      (membrane) lipids and proteins were rapidly produced. After 2 days, the contents
      of these primary metabolites, as well as the nitrogen consumption rate and the
      overall biomass production rate, had returned to values equivalent to those of
      cells grown under nitrogen-replete conditions, indicating that culture recovery
      required 2 days. Nitrogen resupply was immediately followed by rapid degradation
      of TAG and starch, suggesting that these metabolites served as carbon and energy
      source for the recovery process. Also, the secondary carotenoids canthaxanthin
      and ketolutein were rapidly degraded upon nitrogen resupply, whereas degradation
      of astaxanthin, the main secondary carotenoid, started only when the cells were
      fully recovered 2 days after nitrogen resupply. This is the first time that such
      culture recovery has been described in detail and, moreover, that astaxanthin was
      found to be not immediately degraded after nitrogen resupply. The observed rapid
      recovery of C. zofingiensis and the delay in astaxanthin degradation suggest that
      a repeated batch cultivation may result in a higher secondary carotenoid
      productivity than a series of classical single batch cultivations. 

PMID- 25370994
TI  - Concomitant administration of nitrous oxide and remifentanil reduces oral tissue
      blood flow without decreasing blood pressure during sevoflurane anesthesia in
      rabbits.
AB  - PURPOSE: To determine whether continuous administration of nitrous oxide and
      remifentanil-either alone or together-alters blood flow in oral tissues during
      sevoflurane anesthesia. METHODS: Eight male tracheotomized Japanese white rabbits
      were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR),
      systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
      pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood
      flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow
      (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood
      flow (LBF) were recorded in the absence of all test agents and after
      administration of the test agents (50 % nitrous oxide, 0.4 MUg/kg/min
      remifentanil, and their combination) for 20 min. RESULTS: Nitrous oxide increased
      SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did
      not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except
      DBP. Combined administration of nitrous oxide and remifentanil recovered SBP,
      DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained
      lower than control values. CONCLUSIONS: Our findings suggest that concomitant
      administration of nitrous oxide and remifentanil reduces blood flow in oral
      tissues without decreasing blood pressure during sevoflurane anesthesia in
      rabbits.

PMID- 25370995
TI  - Combined circumferential and longitudinal left ventricular systolic dysfunction
      in patients with asymptomatic aortic stenosis.
AB  - BACKGROUND: Early detection of left ventricular (LV) systolic dysfunction is
      pivotal in the management of patients with aortic stenosis (AS). LV
      circumferential and/or longitudinal shortening may be impaired in these patients
      despite LV ejection fraction is preserved. We focused on prevalence and factors
      associated with combined impairment of circumferential and longitudinal
      shortening (C&L) in asymptomatic AS patients. METHODS: Echocardiographic and
      clinical data from 200 patients with asymptomatic AS of any degree without
      history of heart failure and normal LV ejection fraction were analyzed. C&L were
      evaluated by mid-wall shortening (MS) and tissue Doppler mitral annular peak
      systolic velocity (S'), and classified low if <16.5% and if <8.5 cm/sec,
      respectively (10th percentiles of controls). RESULTS: Combined C&L dysfunction
      was detected in 72 patients (36%). The variables associated with this condition
      were higher LV mass (OR 1.02 [CI 1.01-1.04], P = 0.03), concentric LV geometry
      (OR 4.30 [CI 1.79-10.34], P = 0.001), increasing pulmonary artery wedge pressure
      (by E/e' ratio; OR 1.11 [CI 1.04-1.19], P = 0.001). The relation of MS and peak
      S' was linear and slightly significant in the whole population (r = 0.23; F
      statistic=0.001), absent in patients with C&L dysfunction (r = 0.04; F = ns),
      negative (linear model) in the subgroup of patients without C&L dysfunction (r = 
      0.22; F = 0.02). CONCLUSIONS: C&L dysfunction is present in more than one-third
      of patients with asymptomatic AS and is associated with concentric LV geometry
      and higher degree of diastolic dysfunction. The relation between MS and peak S'
      largely varies in the subgroups with different C&L function.

PMID- 25370996
TI  - Human age-related cataracts: epigenetic suppression of the nuclear factor
      erythroid 2-related factor 2-mediated antioxidant system.
AB  - Human aging is a multifactorial process. The most prominent effects of aging
      include visual impairments, particularly age-related cataracts (ARC). Several
      studies have reported that oxidative stress and failure of the antioxidant system
      are the major factors contributing to lens oxidation. The present study focused
      on the nuclear factor erythroid 2-related factor 2 (Nrf2)/kelch-like ECH
      associated protein 1 (Keap1)-mediated antioxidant system and its failure in aging
      lenses. The protein levels, gene expression and methylation status of Nrf2/Keap1
      were investigated in human lenses from different age groups. Human lens
      epithelial cells were collected from different age groups ranging between 15 and
      80 years and cataract lenses were also collected for the comparative study. The
      results demonstrated significantly lower protein and gene expression levels of
      Nrf2 in lenses of increasing age; however, a significant increase in the
      expression of the Nrf2 regulator, Keap1, was observed. Based on these results,
      the present study then aimed to investigate the underlying mechanisms. A gene
      specific DNA methylation study was performed in cataractous lenses of different
      ages, which revealed significantly increased levels of demethylated DNA in the
      Keap1 promoter with increasing age. Notably, the results from cataract lenses
      demonstrated significant demethylation of the Keap1 promoter, which was also
      reflected in the results of clear lenses aged between 66 and 80 years. These
      results suggested that demethylation in the Keap1 promoter region activated the
      expression of the Keap1 protein, which then increased the targeting of Nrf2 for
      proteasomal degradation. Therefore, decreased activity of Nrf2 restrained the
      transcription of its downstream antioxidant enzyme and led to the failure of the
      antioxidant system, ultimately leading to the formation of ARCs. 

PMID- 25370998
TI  - About the cancer research network.

PMID- 25370997
TI  - Welcome message from conference co-convenors.

PMID- 25370999
TI  - Keynote speakers.

PMID- 25371000
TI  - National invited speakers.

PMID- 25371001
TI  - Program.

PMID- 25371003
TI  - SYDNEY CANCER CONFERENCE, 26 November 2014, The University of Sydney.

PMID- 25371002
TI  - Public lecture.

PMID- 25371006
TI  - Conference venue.

PMID- 25371004
TI  - Sponsors and exhibitors.

PMID- 25371007
TI  - Safety of ultrasound-guided fine-needle aspiration of the feline pancreas: a case
      control study.
AB  - The safety of fine-needle aspiration (FNA) of the feline pancreas has not been
      reported. The incidence of complications following ultrasound-guided pancreatic
      FNA in 73 cats (pancreatic aspirate [PA] cats) with clinical and ultrasonographic
      evidence of pancreatic disease was compared with complications in two groups of
      matched control cats also diagnosed with pancreatic disease that either had
      abdominal organs other than the pancreas aspirated (control FNA, n = 63) or no
      aspirates performed (control no FNA, n = 61). The complication rate within 48 h
      of the ultrasound and/or aspirate procedure did not differ among the PA cats
      (11%), control FNA (14%) or control no FNA (8%) cats. There was no difference in
      rate of survival to discharge (82%, 84% and 83%, respectively) or length of
      hospital stay among groups. The cytologic recovery rate for the pancreatic
      samples was 67%. Correlation with histopathology, available in seven cases, was
      86%. Pancreatic FNA in cats is a safe procedure requiring further investigation
      to establish diagnostic value. 

PMID- 25371008
TI  - Effect of point sampling density in quantifying mouse lung emphysema.
AB  - In the official joint policy document of the American Thoracic Society and
      European Respiratory Society (Hsia et al., Am J Respir Crit Care Med 181:394
      418), the need for proper stereologic assessment of lungs was emphasized. In this
      document it was emphasized that for the quantitative analysis of lung histologic
      sections, one of the most robust and reliable methods is point and intercept
      counting (Knudsen et al., J Appl Physiol 108:412-421). One of the practical
      aspects of this method is how many points or intercepts are needed. The answer to
      this question has been considered from a theoretical perspective, and it depends
      on the relative magnitudes of the methodological and biologic variabilities.
      Although it is generally accepted that in a normal lung, one needs only 100-200
      points to sufficiently lower the methodological variability, given the increased
      variability often seen in experimental emphysematous lung injury, the requisite
      number of points of intercepts has not been evaluated. In this study, we examined
      this question by focusing on some of the relevant sampling levels in mice with
      extensive elastase-induced emphysema. Using fixed samples of tissue blocks, we
      varied the number of sampling points or intercepts from about 25 to 1,000 in
      control and emphysematous lungs. Our results show that, at the sampling levels
      investigated, even with the increased heterogeneity in the lung tissue damage
      caused by elastase, the number of sampling points needed to detect changes is
      similar to what is needed for control mice.

PMID- 25371009
TI  - Marked First Degree Atrioventricular Block: an extremely prolonged PR interval
      associated with Atrioventricular Dissociation in a young Nigerian man with Pseudo
      Pacemaker Syndrome: a case report.
AB  - BACKGROUND: The diagnosis of Marked First Degree Atrioventricular Block is made
      with electrocardiogram when PR interval >=0.30 s. A PR interval of up to 0.48 s
      had been reported in literature. Data is sparse on an extremely prolonged PR
      interval associated with Atrioventricular Dissociation and Pseudo-Pacemaker
      Syndrome. Electrocardiogram with this type of uncommon features poses diagnostic
      and management challenges in clinical practice. CASE PRESENTATION: We report a
      case of a 22 year old Nigerian male from Igbo ethnic group who presented himself
      for medical screening with a history of exercise intolerance, occasional
      palpitation and fainting spells. He has no history of cough, orthopnoea,
      paroxysmal nocturnal dyspnoea nor body swelling. A physical examination revealed
      that the patient has a pulse rate of 64 beats per minute, blood pressure of
      110/70 mmHg and soft heart sounds. Standard 12-lead electrocardiogram showed an
      uncommon Marked First Degree Atrioventricular Block with an extremely prolonged
      PR interval of 0.56 s. Long rhythm strips of the electrocardiogram showed
      extremely prolonged PR interval associated with Atrioventricular Dissociation and
      variable degrees of Atrioventricular Block (Mobitz type I and II). CONCLUSIONS:
      An extremely prolonged PR interval may occur in First Degree Atrioventricular
      Block and it may be associated with Atrioventricular Dissociation and Pseudo
      Pacemaker Syndrome which may pose diagnostic and management challenges. This
      suggests that not all cases of First Degree Atrioventricular Block are benign and
      so should be sub-classified based on degree of PR interval prolongation and
      associated electrical abnormalities.

PMID- 25371010
TI  - Culture phases, cytotoxicity and protein expressions of agarose hydrogel induced
      Sp2/0, A549, MCF-7 cell line 3D cultures.
AB  - Advancements in cell cultures are occurring at a rapid pace, an important
      direction is culturing cells in 3D conditions. We demonstrate the usefulness of
      agarose hydrogels in obtaining 3 dimensional aggregates of three cell lines,
      A549, MCF-7 and Sp2/0. The differences in culture phases, susceptibility to
      cisplatin-induced cytotoxicity are studied. Also, the 3D aggregates of the three
      cell lines were reverted into 2D cultures and the protein profile differences
      among the 2D, 3D and revert cultures were studied. The analysis of protein
      profile differences using UniProt data base further augment the usefulness of
      agarose hydrogels for obtaining 3D cell cultures. 

PMID- 25371011
TI  - Blastema cells derived from New Zealand white rabbit's pinna carry stemness
      properties as shown by differentiation into insulin producing, neural, and
      osteogenic lineages representing three embryonic germ layers.
AB  - Stem cells (SCs) are known as undifferentiated cells with self-renewal and
      differentiation capacities. Regeneration is a phenomenon that occurs in a limited
      number of animals after injury, during which blastema tissue is formed. It has
      been hypothesized that upon injury, the dedifferentiation of surrounding tissues
      leads into the appearance of cells with SC characteristics. In present study,
      stem-like cells (SLCs) were obtained from regenerating tissue of New Zealand
      white rabbit's pinna and their stemness properties were examined by their
      capacity to differentiate toward insulin producing cells (IPCs), as well as
      neural and osteogenic lineages. Differentiation was induced by culture of SLCs in
      defined medium, and cell fates were monitored by specific staining, RT-PCR and
      flow cytometry assays. Our results revealed that dithizone positive cells, which
      represent IPCs, and islet-like structures appeared 1 week after induction of
      SLCs, and this observation was confirmed by the elevated expression of Ins, Pax6
      and Glut4 at mRNA level. Furthermore, SLCs were able to express neural markers as
      early as 1 week after retinoic acid treatment. Finally, SLCs were able to
      differentiate into osteogenic lineage, as confirmed by Alizarin Red S staining
      and RT-PCR studies. In conclusion, SLCs, which could successfully differentiate
      into cells derived from all three germ layers, can be considered as a valuable
      model to study developmental biology and regenerative medicine. 

PMID- 25371013
TI  - Restoration of portal flow with a pericholedochal varix in adult living donor
      liver transplantation for patients with total portosplenomesenteric thrombosis.

PMID- 25371012
TI  - Continuity of states between the cholesteric -> line hexatic transition and the
      condensation transition in DNA solutions.
AB  - A new method of finely temperature-tuning osmotic pressure allows one to identify
      the cholesteric -> line hexatic transition of oriented or unoriented long
      fragment DNA bundles in monovalent salt solutions as first order, with a small
      but finite volume discontinuity. This transition is similar to the osmotic
      pressure-induced expanded -> condensed DNA transition in polyvalent salt
      solutions at small enough polyvalent salt concentrations. Therefore there exists
      a continuity of states between the two. This finding, together with the
      corresponding empirical equation of state, effectively relates the phase diagram
      of DNA solutions for monovalent salts to that for polyvalent salts and sheds some
      light on the complicated interactions between DNA molecules at high densities. 

PMID- 25371015
TI  - Highly efficient modular metal-free synthesis of 3-substituted 2-quinolones.
AB  - A modular approach to 3-substituted 2-quinolones via a cascade annulation
      reaction between 4-nitroketones and hydrazines has been developed. 

PMID- 25371014
TI  - Effects of antiviral therapy on the cellular immune response in patients with
      chronic hepatitis B.
AB  - A weak T-cell immune response to the hepatitis B virus (HBV) is hypothesized to
      be the primary cause of chronic HBV infection. Emerging evidence suggests that
      long-term effective antiviral therapy restores the HBV-specific T-cell response
      from exhaustion. However, the extent to which the cellular immune response can be
      restored following the persistent suppression of HBV replication by antiviral
      therapy remains unclear. In order to investigate this question, 46 patients with
      chronic hepatitis B (CHB) treated with nucleos(t)ide analogues who demonstrated
      persistent suppression of HBV replication [defined as undetectable HBV DNA,
      hepatitis B e antigen (HBeAg) negative and adherence to antiviral therapy], 22
      untreated CHB patients, 15 patients with acute hepatitis B (AHB) and 10 healthy
      adults were recruited. HBV-specific interferon-gamma enzyme-linked immunospot
      (IFN-gamma ELISPOT) assay and HBV-specific T-cell proliferation analysis were
      performed with a panel of overlapping peptides covering the envelope and core
      antigens. Data from this study showed that the HBV-specific immune responses to
      the peptide pools of the envelope and core protein in the treated patients were
      stronger than those in the untreated CHB patients, but significantly weaker than
      those in the AHB patients and healthy adults. A higher frequency of response to S
      than C peptide pools was confirmed by the IFN-gamma ELISPOT assay in the treated
      CHB patients. The restoration of antiviral immunity was clearly associated with a
      reduction in HBV DNA and the duration of HBV DNA suppression. In conclusion, the
      HBV-specific immune responses in the CHB patients can be significantly restored
      from exhaustion following the persistent suppression of HBV replication as a
      result of antiviral treatment with nucleos(t)ide analogues.

PMID- 25371016
TI  - [Influencing factors on the length of stay in lumbar spine surgery : analysis of
      the German spine registry].
AB  - INTRODUCTION: Spinal disc herniation, lumbar spinal stenosis and
      spondylolisthesis are known to be leading causes of lumbar back pain. The cost of
      low back pain management and related operations are continuously increasing in
      the healthcare sector. There are many studies regarding complications after spine
      surgery but little is known about the factors predicting the length of stay in
      hospital. The purpose of this study was to identify these factors in lumbar spine
      surgery in order to adapt the postoperative treatment. MATERIAL AND METHODS: The
      current study was carried out as a post hoc analysis on the basis of the German
      spine registry. Patients who underwent lumbar spine surgery by posterior surgical
      access and with posterior fusion and/or rigid stabilization, whereby procedures
      with dynamic stabilization were excluded. Patient characteristics were tested for
      association with length of stay (LOS) using bivariate and multivariate analyses.
      RESULTS: A total of 356 patients met the inclusion criteria. The average age of
      all patients was 64.6 years and the mean LOS was 11.9 +/- 6.0 days with a range
      of 2-44 days. Independent factors that were influencing LOS were increased age at
      the time of surgery, higher body mass index, male gender, blood transfusion of 1
      2 erythrocyte concentrates and the presence of surgical complications.
      CONCLUSION: Identification of predictive factors for prolonged LOS may allow for
      estimation of patient hospitalization time and for optimization of postoperative
      care. In individual cases this may result of a reduction in the LOS.

PMID- 25371018
TI  - Effects of task difficulty during dual-task circle tracing in Huntington's
      disease.
AB  - Huntington's disease (HD) is associated with impairments in dual-task
      performance. Despite that, only a few studies have investigated dual-tasking in
      HD. We examined dual-task performance in 15 participants in the early stages of
      HD and 15 healthy controls. Participants performed direct circle tracing (able to
      view arm) and indirect circle tracing (arm obscured) either on their own (single
      tasks) or paired with serial subtraction by twos or threes (dual tasks). Overall,
      our results suggested that HD participants were significantly slower and less
      accurate than controls. Both groups were slower and less accurate when performing
      indirect circle tracing compared with direct circle tracing. HD participants
      experienced greater dual-task interference in terms of accuracy when performing
      direct circle tracing compared with indirect circle tracing. Despite that,
      controls were more inclined to speed-accuracy trade-offs compared with HD
      participants. Importantly, unlike controls, HD participants were not
      disproportionately faster when performing direct circle tracing as a single task
      compared with the dual-task conditions. Our results suggest that simple tasks
      place greater attentional demands on HD participants compared with controls.
      These findings support that impaired automaticity may be responsible for some of
      the attentional deficits manifested in HD.

PMID- 25371019
TI  - Epidemiology, disease burden and outcomes of cirrhosis in a large secondary care
      hospital in South Auckland, New Zealand.
AB  - BACKGROUND: Liver cirrhosis is an important cause of morbidity and mortality;
      however, little is known about its impact in New Zealand. AIMS: We aim to
      determine the disease burden, epidemiology and outcomes of cirrhotic patients.
      METHODS: This is a retrospective study of cirrhosis patients under secondary
      public hospital care in a geographically defined region, between the years 2000
      and 2011. Cirrhosis complications and mortality was recorded. Poisson log-linear
      regression analysis was performed for incidence rate ratio (IRR) and Cox
      regression analysis was used to analyse time-related events. RESULTS: Seven
      hundred and forty-six cirrhotic patients were analysed; most were European/Other
      (39.9%), Pacific islanders (21.6%), Southeast Asian/Chinese (17.8%) and Maori
      (12.3%). 68.4% were male. The common primary aetiologies for cirrhosis were
      chronic hepatitis B (CHB) cirrhosis (37.3%), alcoholic liver disease (ALD)
      cirrhosis (24.1%), chronic hepatitis C (CHC) cirrhosis (22.3%) and non-alcoholic
      fatty liver disease (NAFLD) cirrhosis (16.4%). The hepatocellular carcinoma (HCC)
      mortality rates were highest in NAFLD and CHB cirrhosis groups (3.0 and 3.1 per
      100 patient-year respectively), compared with ALD and CHC groups (2.2 and 1.4 per
      100 patient-year, all P < 0.05 respectively). Patients with ALD and NAFLD
      cirrhosis had the highest all-cause and non-HCC mortality rate compared with
      viral hepatitis cirrhosis groups. The IRR for HCC incidence, liver-related
      mortality and HCC mortality were 1.087, 1.098 and 1.114, respectively (all P <
      0.001), suggesting increasing incidence and disease burden over the study period.
      CONCLUSION: The number of cirrhotic patients in secondary care is increasing
      steadily. Cirrhosis complications and mortality rates are also rising,
      particularly the incidence and mortality of HCC.

PMID- 25371017
TI  - Differential gene expression of cytokines and neurotrophic factors in nerve and
      skin of patients with peripheral neuropathies.
AB  - Pathophysiologically relevant alterations in cytokine and neurotrophic factor
      levels have been reported in neuropathy subtypes. We characterized gene
      expression profiles of pro- and anti-inflammatory cytokines and neurotrophic
      factors in nerve and skin samples of patients with neuropathies of different
      etiologies. We prospectively studied 133 patients with neuropathies and compared
      data between subtypes and with healthy controls. All patients underwent sural
      nerve and/or skin punch biopsy at the lateral thigh and lower leg; controls
      received skin punch biopsies. Gene expression of pro- and anti-inflammatory
      cytokines (IL-1beta, IL-2, IL-6, TNF, IL-10), neurotrophic factors (BDNF, NGF,
      NT3, TrkA), and erythropoietin with the erythropoietin receptor (Epo, EpoR) was
      analyzed. Sural nerve gene expression of the investigated cytokines and
      neurotrophic factors did not differ between neuropathies of different etiologies;
      however, IL-6 (p < 0.01) and IL-10 (p < 0.05) expression was higher in painful
      compared to painless neuropathies. Skin IL-6 and IL-10 gene expression was
      increased in patients compared to controls (p < 0.05), and IL-10 expression was
      higher in lower leg skin of patients with non-inflammatory neuropathies compared
      to inflammatory neuropathies (p < 0.05). Proximal and distal skin neurotrophic
      factor and Epo gene expression of patients with neuropathies was reduced compared
      to controls (NGF, NT3, Epo; p < 0.05). Neuropathies are associated with an
      increase in cytokine expression and a decrease in neurotrophic factor expression
      including nerve and skin.

PMID- 25371020
TI  - The experience of engaging with mental health services among young people who
      hear voices and their families: a mixed methods exploratory study.
AB  - BACKGROUND: Research shows us that auditory hallucinations or 'hearing voices'
      may be more common than previously thought, particularly in childhood and
      adolescents. Importantly, not all individuals are affected negatively by their
      voice hearing experiences, yet child and adolescent mental health services
      (CAMHS) have traditionally understood voice hearing as a symptom of psychosis and
      severe mental illness, with implications for the way interventions are offered.
      The purpose of the present study was to gain an understanding of how young people
      who hear voices and their families find engaging with mental health service, and
      to better understand their experience of mental health professionals. METHODS: A
      two-stage, mixed methods study was used. In the first stage, semi-structured
      interviews were carried out with two young people and their parents who had
      engaged with mental health services, and the collected data were analysed using
      Interpretative Phenomenological Analysis (IPA). In the second stage, a
      questionnaire was designed to test the generalizability of the themes arising
      from the first stage, and was completed online by 32 young voice hearers and 27
      parents. RESULTS: IPA analysis produced 4 themes: (1) The struggle to understand
      the hearing voices phenomenon; (2) Battle with the Mental Health Services; (3)
      'Stuck in a limbo'; and (4) The wish for a more holistic approach from mental
      health services and professionals. The survey partially confirmed the findings of
      study one, with young people and parents finding useful information difficult to
      come by, and many reported feeling lost in CAMHS. Additionally, young voice
      hearers and parents often felt not listened to, and many parents expressed the
      need for a holistic care, whilst young people wanted a more normalizing and less
      stigmatizing experience. CONCLUSIONS: Young people and their families had varying
      experiences of mental health services. Whilst the survey showed that some young
      people and their families had more positive experiences, many expressed
      dissatisfaction. To fulfil the needs of young people and their families, mental
      health services would benefit from developing alternative approaches to voice
      hearing and running support groups that could form part of a 'normalising' and
      'holistic care' package.

PMID- 25371021
TI  - Adenomyoepithelial Adenosis of Breast: A Rare Case Report.
AB  - Myoepithelial cells of the breast and their hyperplasia is found in many benign
      conditions resulting in a spectrum of lesions of myoepitheliosis to myoepithelial
      carcinoma. We present a rare case of adenomyoepithelial adenosis in a 17-year-old
      female who presented with a palpable right breast lump. Although considered
      benign, adenomyoepithelial lesions have a high chance of recurrence due to
      inadequate excision. Recurrence and even metastasis are therefore important
      issues in the follow-up of adenomyoepithelial lesions.

PMID- 25371022
TI  - Lipofibromatous Hamartoma of the Median Nerve in Association with or without
      Macrodactyly.
AB  - Lipofibromatous hamartoma is a rare tumour-like condition involving the
      peripheral nerves, particularly the median nerve. It commonly affects the volar
      aspect of the hands, wrists and forearms of young adults. Most patients present
      either early with macrodactyly or later with a forearm mass lesion or symptoms
      consistent with compressive neuropathy of the involved nerve. The clinical and
      histomorphological findings of five patients with lipofibromatous hamartoma of
      the median nerve are analysed. The presentation, pathological features and
      differential diagnosis of neural lipofibromas are discussed along with a brief
      review of the literature. Of the five cases of lipofibromatous hamartoma, all
      were seen to involve the median nerve, occurring in four women and one man. Three
      of these cases had associated macrodactyly which was congenital in two and was
      seen from childhood in one. Microscopic examination showed fibrofatty tissue
      surrounding and infiltrating along the epineurium and perineurium. The nerve
      bundles were splayed apart by the infiltrating adipose tissue. Neural
      fibrolipomatous hamartoma is a benign condition. Most respond to conservative
      management with surgical exploration, biopsy and carpal tunnel release to
      decompress the nerve. Correct diagnosis of this uncommon lesion is important as
      surgical excision of the lesion may lead to loss of neurological function.

PMID- 25371023
TI  - Lhermitte-Duclos Disease: A Rare Lesion with Variable Presentations and Obscure
      Histopathology.
AB  - Since Lhermitte-Duclos is a quite rare disorder with both neoplastic and
      hamartomatous features, clinical and pathological diagnosis can sometimes be
      challenging. For the pathologist it is of extreme importance to be aware of
      variable clinical and histopathological presentations of such a rare lesion
      particularly to differentiate it from the low-grade glial and neuronal tumors. We
      present four cases of Lhermitte-Duclos in a histopathological perspective.
      Although enlargement of the internal granular layer of the cerebellum is a
      consistent finding in our cases, morphological severity was highly variable and
      in some cases the enlargement was insignificant. Frozen sections of one case did
      not reveal diagnostic findings. The vacuolar change observed in the paraffin
      sections was obscure in the frozen. Pathological diagnosis of Lhermitte-Duclos
      disease can be extremely difficult in the absence of proper clinical information
      and the pathologist should be watchful for any irregularity in the internal
      granular layer in evaluating the cerebellar tissue which is otherwise normal.

PMID- 25371024
TI  - Incidental bladder lipoma: a case report and review of the literature.
AB  - Conventional lipoma is the most common benign mesenchymal neoplasm in adults.
      However, bladder lipoma is a rare tumor. We report an incidental 0.5-cm, mucosal,
      bladder lipoma in a 75-year-old man, successfully treated with endoscopic
      excision. The tumor was found during the extension study of a high-grade
      urothelial carcinoma of the renal pelvis. A review of the published cases,
      including the present report, yielded a total of 16. Conclusions on this review
      are presented. The case is being reported because its rarity and to highlight the
      importance of complete workup to clarify associated disorders that may suggest
      extension of a malignant process.

PMID- 25371025
TI  - Improving the criteria for appropriateness of total joint replacement surgery:
      comment on the article by Riddle et Al.

PMID- 25371026
TI  - Role of periodontal disease in bisphosphonate-related osteonecrosis of the jaws
      in ovariectomized rats.
AB  - OBJECTIVE: This study aimed to investigate the role of progressive periodontal
      disease in inducing bisphosphonate-related osteonecrosis of the jaws (BRONJ)
      using an ovariectomized (OVX) rat model mimicking human intracortical remodeling
      process. MATERIALS AND METHODS: Thirty 12-week-old Spraque-Dawly (SD) female rats
      were randomly assigned into two groups. All rats underwent bilateral ovariectomy.
      Six weeks after surgery, zoledronic acid (ZA) or vehicle control was administered
      intraperitoneally for 12 weeks. On the same day of injection, a cotton ligature
      was placed subgingivally around the first left lower molar to induce
      periodontitis. All animals were sacrificed 12 weeks after injection. The entire
      mandibles were harvested for micro-computed tomography (micro-CT) and
      histological examinations. RESULTS: Micro-CT examination showed that ligature
      placement caused significant alveolar bone loss both in ZA (0.63 +/- 0.13 vs.
      0.38 +/- 0.06 mm, P < 0.001) and in control (0.88 +/- 0.19 vs. 0.40 +/- 0.06 mm,
      P < 0.001) groups. Whereas in the ZA group, bone loss was attenuated compared
      with the control group (P < 0.01); the bone mineral density in the ZA group (1.00
      +/- 0.02 g/cm(3)) was significantly higher than that in vehicle control group
      (0.96 +/- 0.03 g/cm(3), P < 0.001). Histological examination found necrotic bone
      tissue with extensive, empty lacunae in two of 15 rats in ZA group, but in none
      of the control group. CONCLUSION: Bisphosphonates inhibit alveolar bone
      resorption in progressive periodontal disease, which might benefit the management
      of periodontitis, but increase the risk of developing BRONJ.

PMID- 25371028
TI  - Innovative platform and incentive mechanism are the keys for electronic waste
      collection in developing countries.

PMID- 25371027
TI  - Estrogenic potency of bisphenol S, polyethersulfone and their metabolites
      generated by the rat liver S9 fractions on a MVLN cell using a luciferase
      reporter gene assay.
AB  - BACKGROUND: Bisphenol A (BPA) is an applied chemical that is used in many
      industrial fields and is a potential endocrine disruption chemical (EDC) that is
      found in the environment. Bisphenol S (BPS) and polyethersulfone (PES) have been
      suggested as putative BPA alternatives. In this study, the estrogenic potency
      induced by the binding of 17-beta-estradiol (E2), BPA, BPS, PES and their
      metabolites formed by the rat liver S9 fraction to the human estrogen receptor
      (ER) was estimated. METHODS: We used an in vitro bioassay based on the luciferase
      reporter assay in MVLN cells to evaluate the estrogenic activity of 17-beta
      estradiol (E2), BPA, BPS, PES (E2: 0.001 to 0.3 nM; BPA, BPS and PES: 0.0001 to 5
      microM) and their metabolites (E2: 0.05 microM; BPA, BPS and PES: 0.1 mM)
      according to incubation times (0, 20 and 40 min). After chemical treatment to
      MVLN cells for 72 hrs, and the cell viability and luciferase intensity induced
      were estimated, from which the estrogenic activity of the chemicals tested was
      evaluated. RESULTS: BPA and BPS induced estrogenic activity whereas PES did not
      show any estrogenic activity in the concentrations tested. In an in vitro assay
      of metabolites, BPA metabolites displayed comparable estrogenic activity with BPA
      and metabolites of both BPS and PES showed increasing estrogenic activity.
      CONCLUSIONS: The results suggest that the metabolites of BPS and PES have
      estrogenic potential and the need for the assessment of both chemicals and their
      metabolites in other EDC evaluation studies. The estrogenic potency of PES and
      its metabolites is the first report in our best knowledge.

PMID- 25371029
TI  - Laser acupuncture effect on fetal well-being during induction of labor.
AB  - Labor induction with traditional drugs is sometimes associated with fetal
      complications as fetal distress or death. The aim of this study was to evaluate
      the effect of labor induction by laser acupuncture on fetal well-being in post
      term pregnancy. Nulliparous women at 40 weeks or greater were randomized to sham
      laser group versus laser acupuncture group. Each session consisted of laser
      application on bilateral points LI 4, SP 6, BL 31, and BL 32. The study was
      conducted in Cairo University, National Institute of Laser Enhanced Sciences.
      Sixty nulliparous women were randomized into laser acupuncture group n = 30 and
      control group n = 30. Women were treated in both groups in three consecutive days
      in post-date pregnancy. Results (66.6%) showed a significant difference in rate
      of normal vaginal delivery (NVD) between acupuncture group (50%) and control
      group (50%) (p = 0.002). There was no significant difference of enrollment
      delivery time between laser acupuncture and sham groups (p > 0.05). There were
      six cases of cesarean section (CS) due to no fetal movement with normal
      cardiotocography (CTG). Laser acupuncture has no effect on fetus, and its effect
      on fetal movement needs more investigations. Laser can induce labor if the
      cervical length is less than 1 cm and dilation (0).

PMID- 25371032
TI  - Metal implant-induced skin ulcer mimicking scrofuloderma.

PMID- 25371033
TI  - The Role of Anxiety and Dissociation in Young Australian Gamblers.
AB  - The aim of the present study was to examine predictors of 'escape style' problem
      gambling among young Australian gamblers. Anxiety and dissociation are considered
      to be predictors of 'escape style' gambling behaviour although this assessment
      has neglected consideration of different modes of gambling. This study builds on
      existing research, to examine the role of anxiety and dissociation in the
      gambling habits of young Australian male and female gamblers. One hundred and
      forty-two participants aged between 18 and 35 years self-selected and completed
      an online questionnaire. The hypothesis that gamblers would have similar levels
      of dissociation and anxiety despite different modes of gambling was supported.
      The hypothesis that anxiety and dissociation would both together and uniquely
      predict problem gambling behaviour across a range of gambling modalities was
      supported. Further, the hypothesis that there would be an interaction effect
      between anxiety and dissociation such that their presence together would predict
      a higher degree of problem gambling behaviour was supported. Results suggest that
      anxiety and dissociation play an important role in 'escape style' gambling and
      that strategies to combat problem gambling may benefit from research targeting
      anxiety and attempting to rechannel dissociative behaviour into healthier
      pursuits. 

PMID- 25371034
TI  - Sudanese community pharmacy practice and its readiness for change to patient
      care.
AB  - OBJECTIVES: This study aims to describe the current state of Sudanese community
      pharmacy practice and explore the capacity of existing community pharmacies to
      foster the change to pharmaceutical care (PC) and to assess attitude and
      knowledge of community pharmacists regarding PC and identify barriers. METHODS: A
      structured, self-administered, piloted questionnaire was distributed to the
      pharmacists in charge of 274, randomly selected, community pharmacies in Khartoum
      state. The questionnaire included six domains: demographic characteristics,
      organizational structure of community pharmacies, current activities of community
      pharmacists, their attitudes and knowledge regarding PC, and potential barriers.
      Attitude responses were measured by a 5-point Likert scale. KEY FINDINGS:
      Response rate was 67%. Community pharmacies are short on some tools that are
      deemed necessary for PC implementation, e.g. consultation areas. Community
      pharmacists provide mainly product-focused services with no or little PC
      activities. However, there is a highly positive attitude among the majority of
      respondents towards practice change to include PC (mean positive score +/-
      standard deviation = 4.39 +/- 0.73, frequency (%) = 89%). Many barriers to
      implementation of PC were identified, e.g. pharmacists' clinical knowledge and
      lack of understanding of pharmacist's new role. CONCLUSION: Sudanese community
      pharmacists favour practice change to include PC. Successful implementation of PC
      requires substantial organizational and structural changes in community
      pharmacies, including provision of clinical knowledge, strengthening of clinical
      training and new practice standards. This change in practice could benefit from
      involvement of academia, governmental bodies and professional organizations
      working together for the pharmacy profession.

PMID- 25371035
TI  - Interval and continuous exercise regimens suppress neutrophil-derived
      microparticle formation and neutrophil-promoted thrombin generation under hypoxic
      stress.
AB  - Acute hypoxic exposure increases vascular thrombotic risk. The release of
      procoagulant-rich microparticles from neutrophils accelerates the pathogenesis of
      inflammatory thrombosis. The present study explicates the manner in which
      interval and continuous exercise regimens affect neutrophil-derived microparticle
      (NDMP) formation and neutrophil/NDMP-mediated thrombin generation (TG) under
      hypoxic condition. A total of 60 sedentary males were randomized to perform
      either aerobic interval training [AIT; 3-min intervals at 40% and 80% VO2max
      (maximal O2 consumption)] or moderate continuous training (MCT; sustained 60%
      VO2max) for 30 min/day, 5 days/week for 5 weeks, or to a control (CTL) group who
      did not receive any form of training. At rest and immediately after hypoxic
      exercise test (HE, 100 W under 12% O2 for 30 min), the NDMP characteristics and
      dynamic TG were measured by flow cytometry and thrombinography respectively.
      Before the intervention, HE (i) elevated coagulant factor VIII/fibrinogen
      concentrations and shortened activated partial thromboplastin time (aPTT), (ii)
      increased total and tissue factor (TF)-rich/phosphatidylserine (PS)-exposed NDMP
      counts and (iii) enhanced the peak height and rate of TG promoted by
      neutrophils/NDMPs. Following the 5-week intervention, AIT exhibited higher
      enhancement of VO2max than did MCT. Notably, both MCT and AIT attenuated the
      extents of HE-induced coagulant factor VIII/fibrinogen elevations and aPTT
      shortening. Furthermore, the two exercise regimens significantly decreased TF
      rich/PS-exposed NDMP formation and depressed neutrophil/NDMP-mediated dynamic TG
      at rest and following HE. Hence, we conclude that AIT is superior to MCT for
      enhancing aerobic capacity. Moreover, either AIT or MCT effectively ameliorates
      neutrophil/NDMP-promoted TG by down-regulating expression of procoagulant factors
      during HE, which may reduce thrombotic risk evoked by hypoxia. Moreover, either
      AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating
      expression of procoagulant factors during HE, which may reduce thrombotic risk
      evoked by hypoxia.

PMID- 25371036
TI  - Postoperative bladder catheterization based on individual bladder capacity: a
      randomized trial.
AB  - BACKGROUND: Untreated postoperative urinary retention can result in permanent
      lower urinary tract dysfunction and can be prevented by timely bladder
      catheterization. The author hypothesized that the incidence of postoperative
      bladder catheterization can be decreased by using the patient's own maximum
      bladder capacity (MBC) instead of a fixed bladder volume of 500 ml as a threshold
      for catheterization. METHODS: Randomized parallel-arm and single-blinded
      comparative effectiveness trial conducted in 1,840 surgical patients, operated
      under general or spinal anesthesia without an indwelling urinary catheter.
      Patients were randomized to either use their individual MBC (index) or a fixed
      bladder volume of 500 ml (control) as a threshold for postoperative bladder
      catheterization. Preoperatively, the MBC was determined at home by voiding in a
      calibrated bowl. All other bladder volumes were measured by ultrasound.
      Postoperatively, bladder catheterization was performed when spontaneous voiding
      was impossible, and the ultrasound measurement exceeded the threshold for the
      group in which the patient was randomized (500 or MBC). The primary outcome was
      the incidence of bladder catheterization. RESULTS: The average MBC in the control
      group was 582 ml (+/-199 ml) and in the index group 611 ml (+/-209 ml). The
      incidence of catheterization decreased from 11.8% (107 of 909 patients) in the
      control group to 8.6% (80 of 931) in the index group (relative risk 0.73, 95% CI
      0.55 to 0.96, P = 0.025). There were no adverse events in either group.
      CONCLUSIONS: In patients undergoing surgery under general or spinal anesthesia
      using the MBC rather than a fixed 500 ml threshold for bladder catheterization is
      a safe approach that significantly reduces the incidence of postoperative bladder
      catheterizations.

PMID- 25371037
TI  - Effects of ultraprotective ventilation, extracorporeal carbon dioxide removal,
      and spontaneous breathing on lung morphofunction and inflammation in experimental
      severe acute respiratory distress syndrome.
AB  - BACKGROUND: To investigate the role of ultraprotective mechanical ventilation (UP
      MV) and extracorporeal carbon dioxide removal with and without spontaneous
      breathing (SB) to improve respiratory function and lung protection in
      experimental severe acute respiratory distress syndrome. METHODS: Severe acute
      respiratory distress syndrome was induced by saline lung lavage and mechanical
      ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to
      52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway
      pressure release ventilation) with: (1) conventional P-MV with VT ~6 ml/kg (P
      MVcontr); (2) UP-MV with VT ~3 ml/kg (UP-MVcontr); (3) UP-MV with VT ~3 ml/kg and
      SB (UP-MVspont); and (4) UP-MV with VT ~3 ml/kg and pressure supported SB (UP
      MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. RESULTS:
      The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in
      dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to
      40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr;
      (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and
      redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3)
      compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels
      of tumor necrosis factor-alpha (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0
      to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5
      to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7]
      pg/mg, respectively) in dorsal lung zones. CONCLUSIONS: In this model of severe
      acute respiratory distress syndrome, MV with VT ~3 ml/kg and extracorporeal
      carbon dioxide removal without SB slightly reduced lung histologic damage, but
      not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV,
      pressure supported SB increased lung inflammation.

PMID- 25371038
TI  - TNFalpha shedding in mechanically stressed cardiomyocytes is mediated by Src
      activation of TACE.
AB  - Synthesized by the heart under hemodynamic overloading (mechanical stress),
      TNFalpha exerts complex effects on the heart -beneficial as a membrane protein
      and detrimental as a secreted protein, which presents a dilemma in the treatment
      of congestive heart failure. We postulate that by selectively blocking mechanical
      stress-induced cardiomyocyte secretion of TNFalpha, a function of TNFalpha
      converting enzyme (TACE), the detrimental effect of TNFalpha can be mitigated.
      However, the mechanism through which mechanical stress activates TACE in
      cardiomyocytes is unknown. Here, we report a molecular mechanism that mediates
      TACE activation in mechanically stressed cardiomyocytes. We found that the non
      receptor tyrosine kinase Src mediates TACE activation in mechanically stretched
      rat cardiomyocytes by phosphorylating the Tyr-702 residue within the
      intracellular tail of TACE. The rapid activation of Src in mechanically stretched
      cardiomyocytes is followed by TACE phosphorylation on Tyr-702, leading to
      activation of p38 MAPK, a kinase that is an effector of TNFalpha receptor
      activation. Pharmacological inhibition or silencing of Src attenuated stretch
      induced TACE phosphorylation on Tyr-702 and p38 activation. Overexpression of a
      TACE mutant in which Tyr-702 was replaced by alanine (TACE-Y702A) attenuated
      stretch-induced TNFalpha release from cardiomyocytes as well as activation of
      p38. These data suggests that Src mediates TACE activation in mechanically
      stressed cardiomyocytes and this mechanism could be exploited for specific
      blockade of TNFalpha secretion and its detrimental effects in congestive heart
      failure.

PMID- 25371039
TI  - When mixed methods produce mixed results: integrating disparate findings about
      miscarriage and women's wellbeing.
AB  - PURPOSE: To discuss an example of mixed methods in health psychology, involving
      separate quantitative and qualitative studies of women's mental health in
      relation to miscarriage, in which the two methods produced different but
      complementary results, and to consider ways in which the findings can be
      integrated. METHODS: We describe two quantitative projects involving statistical
      analysis of data from 998 young women who had had miscarriages, and 8,083 who had
      not, across three waves of the Australian Longitudinal Study on Women's Health.
      We also describe a qualitative project involving thematic analysis of interviews
      with nine Australian women who had had miscarriages. RESULTS: The quantitative
      analyses indicate that the main differences between young women who do and do not
      experience miscarriage relate to social disadvantage (and thus likelihood of
      relatively early pregnancy) and to a lifestyle that makes pregnancy likely: Once
      these factors are accounted for, there are no differences in mental health.
      Further, longitudinal modelling demonstrates that women who have had miscarriages
      show a gradual increase in mental health over time, with the exception of women
      with prior diagnoses of anxiety, depression, or both. By contrast, qualitative
      analysis of the interviews indicates that women who have had miscarriages
      experience deep emotional responses and a long and difficult process of coming to
      terms with their loss. CONCLUSIONS: A contextual model of resilience provides a
      possible framework for understanding these apparently disparate results.
      Considering positive mental health as including the ability to deal
      constructively with negative life events, and consequent emotional distress,
      offers a model that distinguishes between poor mental health and the processes of
      coping with major life events. In the context of miscarriage, women's efforts to
      struggle with difficult emotions, and search for meaning, can be viewed as
      pathways to resilience rather than to psychological distress. Statement of
      contribution What is already known on this subject? Quantitative research shows
      that women who miscarry usually experience moderate depression and anxiety, which
      persists for around 6 months. Qualitative research shows that women who miscarry
      frequently experience deep grief, which can last for years. What does this study
      add? We consider ways in which these disparate findings might triangulate. The
      results suggest a need to distinguish between poor mental health and the
      experience of loss and grief. Adjusting to miscarriage is often emotionally
      challenging but not always associated with poor mental health.

PMID- 25371040
TI  - Intermolecular disulfide bond formation promotes immunoglobulin aggregation:
      investigation by fluorescence correlation spectroscopy.
AB  - Protein aggregation generally results from association between hydrophobic
      regions of individual monomers. However, additional mechanisms arising from
      specific interactions, such as intermolecular disulfide bond formation, may also
      contribute to the process. The latter is proposed to be the initiating pathway
      for aggregation of immunoglobulin (IgG), which is essential for triggering its
      immune response. To test the veracity of this hypothesis, we have employed
      fluorescence correlation spectroscopy to measure the kinetics of aggregation of
      IgG in separate experiments either allowing or inhibiting disulfide formation.
      Fluorescence correlation spectroscopy measurements yielded a diffusion time
      (tau(D)) of ~200 usec for Rhodamine-labeled IgG, corresponding to a hydrodynamic
      radius (R(H)) of 56 A for the IgG monomer. The aggregation kinetics of the
      protein was followed by monitoring the time evolution of tau(D) under conditions
      in which its cysteine residues were either free or blocked. In both cases, the
      progress curves confirmed that aggregation proceeded via the nucleation-dependent
      polymerization pathway. However, for aggregation in the presence of free
      cysteines, the lag times were shorter, and the aggregate sizes bigger, than their
      respective counterparts for aggregation in the presence of blocked cysteines.
      This result clearly demonstrates that formation of intermolecular disulfide bonds
      represents a preferred pathway in the aggregation process of IgG. Fluorescence
      spectroscopy showed that aggregates formed in experiments where disulfide
      formation was prevented denatured at lower concentration of guanidine
      hydrochloride than those obtained in experiments where the disulfides were free
      to form, indicating that intermolecular disulfide bridging is a valid pathway for
      IgG aggregation.

PMID- 25371041
TI  - Missing value imputation in high-dimensional phenomic data: imputable or not, and
      how?
AB  - BACKGROUND: In modern biomedical research of complex diseases, a large number of
      demographic and clinical variables, herein called phenomic data, are often
      collected and missing values (MVs) are inevitable in the data collection process.
      Since many downstream statistical and bioinformatics methods require complete
      data matrix, imputation is a common and practical solution. In high-throughput
      experiments such as microarray experiments, continuous intensities are measured
      and many mature missing value imputation methods have been developed and widely
      applied. Numerous methods for missing data imputation of microarray data have
      been developed. Large phenomic data, however, contain continuous, nominal, binary
      and ordinal data types, which void application of most methods. Though several
      methods have been developed in the past few years, not a single complete
      guideline is proposed with respect to phenomic missing data imputation. RESULTS:
      In this paper, we investigated existing imputation methods for phenomic data,
      proposed a self-training selection (STS) scheme to select the best imputation
      method and provide a practical guideline for general applications. We introduced
      a novel concept of "imputability measure" (IM) to identify missing values that
      are fundamentally inadequate to impute. In addition, we also developed four
      variations of K-nearest-neighbor (KNN) methods and compared with two existing
      methods, multivariate imputation by chained equations (MICE) and missForest. The
      four variations are imputation by variables (KNN-V), by subjects (KNN-S), their
      weighted hybrid (KNN-H) and an adaptively weighted hybrid (KNN-A). We performed
      simulations and applied different imputation methods and the STS scheme to three
      lung disease phenomic datasets to evaluate the methods. An R package
      "phenomeImpute" is made publicly available. CONCLUSIONS: Simulations and
      applications to real datasets showed that MICE often did not perform well; KNN-A,
      KNN-H and random forest were among the top performers although no method
      universally performed the best. Imputation of missing values with low
      imputability measures increased imputation errors greatly and could potentially
      deteriorate downstream analyses. The STS scheme was accurate in selecting the
      optimal method by evaluating methods in a second layer of missingness simulation.
      All source files for the simulation and the real data analyses are available on
      the author's publication website.

PMID- 25371042
TI  - The impact of predive exercise on repetitive SCUBA diving.
AB  - AIM: SCUBA diving frequently involves repetitive exposures. The goal of this
      study was to see how exercise impacts microparticles (MPs), endothelial function
      and venous gas emboli (VGE) throughout multiple dives. METHODS: Sixteen divers in
      two groups (G1 and G2) each completed six dives, three preceded by exercise (EX)
      and three as controls (CON). Blood for MP analysis was collected before and after
      each dive. VGE were monitored via transthoracic echocardiography 30, 60 and 90
      min after surfacing. Exercise before diving consisted of 60-min running including
      eight, 3-min intervals at 90% VO2max. RESULTS: Exercise did not have a
      significant impact on VGE. There was no significant difference in MP counts
      between EX and CON. Both groups experienced a significant decrease in MP counts
      in the last three dives compared to the first three (G1 P = 0.0008, G2 P = 0001).
      Other indices of neutrophil/platelet interaction (dual-positive CD63/41 and
      CD62/41) show a significant increase (P = 0.004 and 0.0001) in G2. CONCLUSION:
      Both groups experienced a significant decrease in MPs at all measurements in the
      second series of dives compared to the first, regardless of the placement of
      exercise. Whether this is related to an effect of suppression of MPs or exercise
      timing is not clear.

PMID- 25371043
TI  - Vitamin D, vascular calcification and mortality among alcoholics.
AB  - AIMS: To analyze the relationship between low vitamin D levels and mortality
      among alcoholics. METHODS: One hundred twenty-eight alcoholic patients admitted
      to our hospital were followed up as outpatients. Nutritional status was evaluated
      measuring percentages of fat and lean mass in different body compartments.
      RESULTS: Lower vitamin D levels were observed in patients with worse liver
      function. Vitamin D was lower in patients with lower total lean mass (Z = 2.8, P
      = 0.005), but it was not related to fat mass. There was a significant trend to
      higher long-term mortality among non-cirrhotics with vitamin D levels below 30
      ng/ml, although Cox's regression model revealed that only Child score and age
      were independently related to mortality. CONCLUSION: Vitamin D deficiency is
      common among alcoholic patients and is associated with low lean mass and liver
      dysfunction. Among non-cirrhotics, serum vitamin D levels below 30 ng/ml are
      associated with a greater long-term mortality.

PMID- 25371045
TI  - Influence of chronic alcohol consumption on histaminergic neurons of the rat
      brain.
AB  - AIMS: To clarify the effect of chronic alcohol consumption on the brain
      histaminergic neurons in rats. METHODS: Male Wistar rats were given 20% ethanol
      as the only source of drinking during 6 months, control rats had a free access to
      water. The samples of hypothalamus were prepared for light and electron
      microscopy accompanied by morphometry to examine the brain histaminergic neurons
      of E2 group. RESULTS: Chronic ethanol consumption increased the amount of
      histologically abnormal forms of histaminergic neurons and decreased the whole
      amount of E2 histaminergic neurons (for 5%). The neuron bodies and nuclei
      increased in size and sphericity, the nuclear/cytoplasmic ratio decreased by 15%.
      The ultrastructural changes in histaminergic neurons demonstrate the activation
      of their nuclear apparatus, both destruction and hypertrophy and hyperplasia of
      organelles, especially lysosomes. Chronic ethanol consumption induces the
      disturbances in cytoplasmic enzymes of neurons: increases the activity of type B
      monoamine oxidase, dehydrogenases of lactate and NADH and, especially, marker
      enzyme of lysosomes acid phosphatase as well as inhibits the activity of
      dehydrogenases of succinate and glucose-6-phosphate. CONCLUSION: Chronic alcohol
      consumption affects significantly the structure and metabolism of the brain
      histaminergic neurons, demonstrating both the neurotoxic effect of ethanol and
      processes of adaptation in those neurons, necessary for their survival.

PMID- 25371044
TI  - Zinc insufficiency mediates ethanol-induced alveolar macrophage dysfunction in
      the pregnant female mouse.
AB  - AIMS: (a) Establish the minimum number of weeks of chronic ethanol ingestion
      needed to perturb zinc homeostasis, (b) Examine intracellular zinc status in the
      alveolar macrophages (AMs) when ethanol ingestion is combined with pregnancy, (c)
      Investigate whether in vitro zinc treatment reverses the effects of ethanol
      ingestion on the AM. METHODS: C57BL/6 female mice were fed a liquid diet (+/-25%
      ethanol-derived calories) during preconception and pregnancy. The control group
      was pair-fed to the ethanol group. In the isolated AMs, we measured intracellular
      AM zinc levels, zinc transporter expression, alternative activation and
      phagocytic index. Zinc acetate was added to some cells prior to analysis.
      RESULTS: Intracellular zinc levels in the AM decreased within 3 weeks of ethanol
      ingestion. After ethanol ingestion prior to and during pregnancy, zinc
      transporter expression and intracellular zinc levels were decreased in the AMs
      when compared with controls. Bacterial clearance was decreased because the AMs
      were alternatively activated. In vitro additions of zinc reversed these effects
      of ethanol. CONCLUSION: Ethanol ingestion prior to and during pregnancy perturbed
      AM zinc balance resulting in impaired bacterial clearance, but these effects were
      ameliorated by in vitro zinc treatments.

PMID- 25371046
TI  - Toilet compost and human urine used in agriculture: fertilizer value assessment
      and effect on cultivated soil properties.
AB  - Toilet compost (TC) and human urine are among natural fertilizers, which raise
      interest due to their double advantages to combine sanitation and nutrient
      recovery. However, combination of urine and TC is not so spread probably because
      the best ratio (urine/TC) is still an issue and urine effect on soil chemical
      properties remains poorly documented. This study aims to determine the best ratio
      of urine and TC in okra cultivation, by targeting higher fertilization effect
      combined with lower impact on soil chemical properties. Based on Nitrogen
      requirement of okra, seven treatments were compared: (T0) no fertilizer, (T1)
      chemical fertilizer (NPK: 14-23-14), (T2) 100% urine, (T3) 100% TC, (T4) ratio of
      75% urine+25% TC, (T5) 50% urine+50% TC and (T6) 25% urine+75% TC. Results
      indicated that T4 (75% urine+25% TC) gave the highest plant height and yield. In
      contrast, T2 (100% urine) gave the lowest results among all treatments,
      indicating toxicity effects on plant growth and associated final yield. Such
      toxicity is confirmed by soil chemical properties at T2 with soil acidification
      and significant increase in soil salinity. In contrast, application of urine
      together with TC mitigates soil acidification and salinity, highlighting the
      efficiency of urine and TC combination on soil chemical properties. However,
      further investigation is necessary to refine better urine/TC ratio for okra
      production.

PMID- 25371047
TI  - Synthesis of tri-, tetra-, and pentacarbonyl derivatives via ozonolysis of 1,4
      dienes and cyclization to polyaromatic systems.
AB  - The aim of this work was the synthesis of polyaromatic systems by cyclization of
      beta-polycarbonyls. Useful synthons for beta-polycarbonyl derivatives are
      branched 1,4-dienes generated by cobalt-catalyzed hydrovinylation of terminal
      alkenes and 2,3-dimethyl-1,3-butadiene. Thus, a series of tri-, tetra-, and
      pentacarbonyl synthons was successfully synthesized. Subsequently, these synthons
      were examined in an ozonolysis/cyclization reaction sequence. Polyaromatic
      derivatives were obtained in good yields and the method was applied in the
      synthesis of the natural product Kwanzoquinone A. 

PMID- 25371048
TI  - The impact of whole blood processing and freezing conditions on the quality of
      therapeutic plasma prepared from whole blood.
AB  - BACKGROUND: The quality of whole blood (WB)-derived plasma preparations has been
      the subject of several studies, but there has been a lack of robust, comparative
      data for the different methods of processing and freezing. STUDY DESIGN AND
      METHODS: Six WB-derived plasma units were pooled and split (n = 16) and frozen
      within either 8 or 24 hours after WB collection, stored at 4 degrees C or at room
      temperature (RT), and then frozen either slowly at -20 degrees C or rapidly to
      below -30 degrees C. Plasma units were tested for fibrinogen, Factor (F)V, FVII,
      FVIII, FXI, and von Willebrand factor (VWF), protein C (PC), protein S (PS)
      activity and free PS, prothrombin time, and partial thromboplastin time. RESULTS:
      FVIII was reduced by 9% to 19% after having been stored for 24 hours irrespective
      of storage temperature. Slow freezing (SF) reduced FVIII by 17% to 25% compared
      to rapid freezing (RF) to below -30 degrees C. Storage temperature, but not 24
      hour storage, decreased PS activity by 20% to 28%. PS activity was 8% to 17%
      lower in plasma units frozen slowly compared to RF. Storage and freezing had no
      influence on free PS. SF caused small losses of FVII and FXI activity.
      CONCLUSION: Twenty-four-hour hold at RT and SF both reduce FVIII levels below 70
      U/dL in many plasma units. PS activity is affected substantially by storage
      temperature and SF, but free PS is not. With regard to plasma quality, freezing
      to below -30 degrees C within 1 hour is superior to SF at -20 degrees C.

PMID- 25371049
TI  - Synergistic effect of combining two nondestructive analytical methods for
      multielemental analysis.
AB  - We developed a new analytical technique that combines prompt gamma-ray analysis
      (PGA) and time-of-flight elemental analysis (TOF) by using an intense pulsed
      neutron beam at the Japan Proton Accelerator Research Complex. It allows us to
      obtain the results from both methods at the same time. Moreover, it can be used
      to quantify elemental concentrations in the sample, to which neither of these
      methods can be applied independently, if a new analytical spectrum (TOF-PGA) is
      used. To assess the effectiveness of the developed method, a mixed sample of Ag,
      Au, Cd, Co, and Ta, and the Gibeon meteorite were analyzed. The analytical
      capabilities were compared based on the gamma-ray peak selectivity and signal-to
      noise ratios. TOF-PGA method showed high merits, although the capability may
      differ based on the target and coexisting elements. 

PMID- 25371050
TI  - Modern reconstructive techniques for abdominal wall defects after oncologic
      resection.
AB  - Resection of abdominal wall tumors often leaves patients with debilitating soft
      tissue defects. Modern reconstructive techniques can be used to restore abdominal
      wall integrity. In this article, we present an overview of preoperative patient
      evaluation, analysis of the defect, surgical planning, and the spectrum of
      available surgical techniques, ranging from simple to complex. The established
      clinical evidence in the field of abdominal wall reconstruction is summarized and
      a case example is provided.

PMID- 25371051
TI  - The Creation of the Canadian Connective Tissue Conference (CCTC): Twenty Years
      on.

PMID- 25371052
TI  - Assessing tumor response after loco-regional liver cancer therapies: the role of
      3D MRI.
AB  - Assessing the tumor response of liver cancer lesions after intraarterial
      therapies is of major clinical interest. Over the last two decades, tumor
      response criteria have come a long way from purely size-based, anatomic methods
      such as the Response Evaluation Criteria in Solid Tumors towards more functional,
      enhancement- and diffusion-based parameters with a strong emphasis on MRI as the
      ultimate imaging modality. However, the relatively low reproducibility of those
      one- and 2D techniques (modified Response Evaluation Criteria in Solid Tumors and
      the European Association for the Study of the Liver criteria) provided the
      rationale for the development of new, 3D quantitative assessment techniques. This
      review will summarize and compare the existing methodologies used for 3D
      quantitative tumor analysis and provide an overview of the published clinical
      evidence for the benefits of 3D quantitative tumor response assessment
      techniques. 

PMID- 25371054
TI  - Redox-responsive organometallic hydrogels for in situ metal nanoparticle
      synthesis.
AB  - A new class of redox active hydrogels composed of poly(ferrocenylsilane)
      polyanion and poly(ethylene glycol) chains was assembled, using a copper-free
      azide-alkyne Huisgen cycloaddition reaction. These organometallic hydrogels
      displayed reversible collapse and reswelling upon chemical oxidation and
      reduction, respectively, and formed relatively well-defined, unaggregated Pd(0)
      nanoparticles (8.2 +/- 2.2 nm) from K2PdCl4 salts. 

PMID- 25371053
TI  - Anti-TNF inhibits the airways neutrophilic inflammation induced by inhaled
      endotoxin in human.
AB  - BACKGROUND: Inhaled endotoxin induces airways'neutrophilia, in human. TNF-a being
      a key cytokine in the response to endotoxin, the effect of anti-TNF on the
      endotoxin-induced neutrophilic response was evaluated among healthy volunteers.
      METHODS: Among a population of 30 healthy subjects, an induced-sputum was
      collected 2 weeks before, and 24 hours after an inhalation of 20 mcg endotoxin
      (E. coli 026:B6). Then, the subjects were randomized into 3 parallel groups
      treated with control, oral methylprednisolone 20 mg/day during 7 days or anti-TNF
      (adalimumab, Humira(r), Abbott) 40 mg s.c.. One week later, an induced-sputum was
      sampled, 24 hours after an inhalation of endotoxin. RESULTS: After endotoxin
      inhalation, the number of total cells, neutrophils and macrophages was
      significantly increased (p <0.001). Compared to the response to endotoxin among
      the control group, anti-TNF inhibited the endotoxin-induced neutrophil influx,
      both in relative (51.3 (+/-6.4)% versus 26.2 (+/-5.3)%, p <0.002) and in absolute
      values (1321 (443-3935) cells/mcL versus 247 (68-906) cells/mcL, p <0.02). The
      endotoxin-induced neutrophilic response was not significantly modified among the
      control group and oral corticosteroid group. CONCLUSIONS: While oral
      corticosteroid had no effect, anti-TNF inhibited the neutrophil influx in sputum,
      induced by inhalation of endotoxin, in human subject. The endotoxin model could
      be an early predictor of clinical efficacy of novel therapeutics. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02252809 (EudraCT2008-005526-37).

PMID- 25371055
TI  - Multiple drug combination of anti-diabetic agents as a predictor for poor
      clinical response to liraglutide.
AB  - AIM: Aim of the study was to retrospectively analyze the clinical parameters that
      contribute to the therapeutic outcome of GLP-1 analogues. METHODS: We enrolled
      106 patients with type 2 diabetes mellitus (T2DM), treated with liraglutide
      (N.=69) or exenatide (N.=37) for longer than three months. The patients were
      divided into two groups: good responders and poor responders to GLP-1 analogues,
      based on pretreatment and post-treatment HbA1c levels. Good responders were those
      whose HbA1c level had decreased by 1% or more, or maintained at less than 7%. All
      other patients were categorized as poor responders. We used univariate and
      multivariate analyses to assess pretreatment parameters between the two groups.
      RESULTS: Approximately 35% of the patients were poor responders. Our analysis of
      the pretreatment clinical parameters revealed that number of anti-diabetic agents
      and use of sulfonylurea were significantly associated with poor response to
      liraglutide (P=0.02 and P=0.03, respectively) in a multivariate analysis. We were
      not able to find any candidate related to clinical response to exenatide.
      CONCLUSION: Our study showed that the therapeutic effects of GLP-1 analogues on
      T2DM patients were heterogeneous. T2DM patients who require multiple anti
      diabetic agents, especially sulfonylurea, do not benefit from liraglutide
      treatment.

PMID- 25371056
TI  - Retinol-binding protein 4, as a negative acute-phase reactant in polycystic ovary
      syndrome.
AB  - AIM: The aim of our study was to compare serum levels of RBP4 in women with PCOS
      to the control group and to understand the relationship among RBP4 and
      biochemical and hormonal parameters related to disease process, especially
      gonadal steroids and markers of inflammation. METHODS: Twenty-eight women with
      PCOS (18 normal weight and 10 obese) and 27 normally menstruating healthy women
      (20 normal weight and 7 obese) were included. RESULTS: Women with PCOS had higher
      RBP4 concentrations. RBP4 levels correlated negatively with LDL, hsCRP and LH in
      women with PCOS and positively with BMI in the control group. When obese PCOS
      were compared to normal weight PCOS, increased CRP levels correlated negatively
      with RBP4 only in the normal weight PCOS group (normal PCOS r=-0.465, P=0.042;
      obese PCOS r=-0.505, P=0.137). Regression analysis of the effects of CRP and BMI
      on RBP4 levels revealed a statistically significant relationship between CRP and
      RBP4 independent of BMI. CONCLUSION: Serum RBP4 levels increased in women with
      PCOS and correlated negatively with CRP, LH and LDL. RBP4 probably acts as a
      negative acute phase reactant in normal weight PCOS. It cannot be used as a
      marker of chronic low grade inflammation in women with PCOS.

PMID- 25371057
TI  - Effect of intravitreal bevacizumab on serum, aqueous, and vitreous humor levels
      of erythropoietin in patients with proliferative diabetic retinopathy.
AB  - AIM: The aim of this study was to evaluate concentrations of erythropoietin (EPO)
      and vascular endothelial growth factor (VEGF) in serum, aqueous and vitreous
      humour of diabetic patients with proliferative retinopathy (PDR) and to verify
      their possible modifications induced by intravitreal injection of bevacizumab
      (IVB). METHODS: This prospective observational study was performed on patients
      who underwent vitrectomy for proliferative diabetic retinopathy and macular hole
      or pucker. The study sample consisted of 33 patients with proliferative diabetic
      retinopathy and 20 non-diabetic patients with macular hole or pucker. EPO and
      VEGF levels in serum, aqueous and vitreous humour were measured in both groups.
      In diabetic patients measures were performed before and after IVB. RESULTS: EPO
      and VEGF levels in aqueous and vitreous humour were markedly increased in
      diabetic patients with PDR as compared with those recorded in the control group
      (P<0.001); contrarily, EPO serum levels were similar in both groups (p=not
      significant). IVB did not affect EPO levels (aqueous 39.1 +/- 29.2 vs. 38.6 +/-
      26.1; vitreous 179.3 +/- 88.3 vs. 131.6 +/- 67.8; serum 9.2 +/- 5.8 vs. 6.9 +/-
      3.7 mUI/mL); conversely, VEGF concentration significantly decreased 15 days after
      IVB in serum and ocular fluids (aqueous 141.6 +/- 12.3 vs. 81.4 +/- 5.4; vitreous
      180.4 +/- 45.8 vs. 95.8 +/- 23.6; serum 113.9 +/- 52.8 vs. 73.2 +/- 65.6 mUI/mL).
      CONCLUSION: These findings demonstrate that the production of VEGF and EPO is
      regulated by different mechanisms. Intraocular levels of EPO in diabetic patients
      were significantly higher than those recorded in serum, suggesting a local
      production. In addition, bevacizumab does not influence intraocular levels of
      EPO.

PMID- 25371059
TI  - Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/beta
      catenin pathway.
AB  - Upon stimulation by Wnt ligands, the canonical Wnt/beta-catenin signalling
      pathway results in the stabilization of beta-catenin and its translocation into
      the nucleus to form transcriptionally active complexes with sequence-specific DNA
      binding T-cell factor/lymphoid enhancer factor (TCF/LEF) family proteins. In the
      absence of nuclear beta-catenin, TCF proteins act as transcriptional repressors
      by binding to Groucho/Transducin-Like Enhancer of split (TLE) proteins that
      function as co-repressors by interacting with histone deacetylases whose activity
      leads to the generation of transcriptionally silent chromatin. Here we show that
      the transcription factor Ladybird homeobox 2 (Lbx2) positively controls the
      Wnt/beta-catenin signalling pathway in the posterior lateral and ventral mesoderm
      of the zebrafish embryo at the gastrula stage, by directly interfering with the
      binding of Groucho/TLE to TCF, thereby preventing formation of transcription
      repressor complexes. These findings reveal a novel level of regulation of the
      canonical Wnt/beta-catenin signalling pathway occurring in the nucleus and
      involving tissue-specific derepression of TCF by Lbx2. 

PMID- 25371061
TI  - Re-visiting the O/Cu(111) system--when metastable surface oxides could become an
      issue!
AB  - Surface oxidation processes are crucial for the functionality of Cu-based
      catalytic systems used for methanol synthesis, partial oxidation of methanol or
      the water-gas shift reaction. We assess the stability and population of the "8"
      structure, a [formula, see text:] oxide phase, on the Cu(111) surface. This
      structure has been observed in X-ray photoelectron spectroscopy and low-energy
      electron diffraction experiments as a Cu(111) surface reconstruction that can be
      induced by a hyperthermal oxygen molecular beam. Using density-functional theory
      calculations in combination with ab initio atomistic thermodynamics and Boltzmann
      statistical mechanics, we find that the proposed oxide superstructure is indeed
      metastable and that the population of the "8"-structure is competitive with the
      known "29" and "44" oxide film structures on Cu(111). We show that the
      configuration of O and Cu atoms in the first and second layers of the "8"
      structure closely resembles the arrangement of atoms in the first two layers of
      Cu2O(110), where the atoms in the "8"-structure are more constricted. Cu2O(110)
      has been suggested in the literature as the most active low index facet for
      reactions such as water splitting under light illumination. If the "8"-structure
      were to form during a catalytic process, it is therefore likely to be one of the
      reactive phases.

PMID- 25371060
TI  - Evaluation of diethylnitrosamine- or hepatitis B virus X gene-induced
      hepatocellular carcinoma with 18F-FDG PET/CT: a preclinical study.
AB  - The aim of this study was to evaluate whether the development of hepatocellular
      carcinoma (HCC) in murine models resembles tumor progression in humans, using non
      invasive molecular imaging methods. Murine HCC models were generated by treating
      mice with diethylnitrosamine (DEN) or by the transgenic expression of hepatitis B
      virus X (HBx) protein (HBx-Tg model). Tumor development was detected using 18F
      fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed
      tomography (CT) and magnetic resonance imaging (MRI). The histopathological
      changes and expression of glucose transporter 1 (Glut1) and hexokinase 2 (HK2)
      were evaluated using hematoxylin and eosin and immunohistochemical staining,
      respectively. Tumor lesions as small as 1 mm in diameter were detected by MRI.
      Tumor development was monitored using 18F-FDG PET/CT at 6.5-10 months after DEN
      treatment or 11-20 months after birth of the HBx-Tg model mice. A correlation
      study between the 18F-FDG uptake levels and expression levels of HK2 and Glut1 in
      developed HCC showed a high 18F-FDG uptake in poorly differentiated HCCs that
      expressed high levels of HK2, in contrast to that in well-differentiated tumors.
      The progression of primary HCCs resembling human HCC in murine models was
      detected and monitored by 18F-FDG PET/CT. The correlation between tumor size and
      SUVmax was verified in the two HCC models. To the best of our knowledge, this is
      the first study to demonstrate that in vivo 18F-FDG uptake varies in HCCs
      according to differentiation grade in a preclinical study.

PMID- 25371062
TI  - Similar preferences for ornamentation in opposite- and same-sex choice
      experiments.
AB  - Selection due to social interactions comprises competition over matings (sexual
      selection stricto sensu) plus other forms of social competition and cooperation.
      Sexual selection explains sex differences in ornamentation and in various other
      phenotypes, but does not easily explain cases where those phenotypes are similar
      in males and females. Understanding such similarities requires knowing how
      phenotypes influence nonsexual social interactions as well, which can be very
      important in gregarious animals, but whose role for phenotypic evolution has been
      overlooked. For example, 'mate choice' experiments often found preferences for
      ornamentation, but have not assessed whether those are strictly sexual or are
      general social preferences. Using choice experiments with a gregarious and
      mutually ornamented finch, the common waxbill (Estrilda astrild), we show that
      preferences for ornamentation in the opposite-sex also extend to same-sex
      interactions. Waxbills discriminated between opposite- and same-sex individuals,
      but most preferences for colour traits were similar when interacting with either
      sex. Similar preferences in sexual and nonsexual associations may be widespread
      in nature, either as social adaptations or as by-product of mate preferences. In
      either case, such preferences may set the stage for the evolution of mutual
      ornamentation and of various other similarities between the sexes.

PMID- 25371063
TI  - Nestin predicts a favorable prognosis in early ampullary adenocarcinoma and
      functions as a promoter of metastasis in advanced cancer.
AB  - Nestin exhibits stemness characteristics and is overexpressed in several types of
      cancers. Downstream signaling of nestin [cyclin-dependent kinase 5 (CDK5) and Ras
      related C3 botulinum toxin substrate 1 (Rac1)] functions in cancer to modulate
      cellular behaviors. We studied the function of nestin in ampullary
      adenocarcinoma. Immunohistochemistry (IHC), reverse transcription-polymerase
      chain reaction, and cDNA microarray of nestin in ampullary adenocarcinoma was
      compared with normal duodenum. CDK5 and Rac1 were assessed by western blotting.
      We hypothesized that nestin/CDK5/Rac1 signaling behaves different in early and
      advanced cancer. We found that the presence of nestin mRNA was increased in the
      early stages of cancer (T2N0 or T3N0) and advanced cancer with lymph node
      metastasis (T4N1). A total of 102 patients were enrolled in the IHC staining.
      Weak nestin expression was correlated with favorable characteristics of cancer,
      decreased incidence of local recurrence and lower risk of recurrence within 12
      months after surgery. Patients with weak nestin expression had the most favorable
      recurrence-free survival rates. Patients with mild to strong nestin expression
      exhibited an advanced behavior of cancer and increased possibility of cancer
      recurrence. The reciprocal expression of nestin and RAC1 were explored using a
      cDNA microarray analysis in the early stages of ampullary adenocarcinoma.
      Increased level of CDK5 with simultaneously decreased expression of Rac1 was
      detected by western blotting of ampullary adenocarcinoma in patients without
      cancer recurrence. The activation of multiple oncogenic pathways, combined with
      the stemness characteristics of nestin, formed a complex network in advanced
      ampullary adenocarcinoma. Our study demonstrated that nestin performs a dual role
      in ampullary adenocarcinoma. Appropriate amount of nestin enhances CDK5 function
      to suppress Rac1 and excessive nestin/CDK5 participates in multiple oncogenic
      pathways to promote cancer invasiveness. Inhibiting nestin in patients who
      exhibit nestin-overexpressed ampullary adenocarcinoma may be a method of
      preventing cancer recurrence.

PMID- 25371064
TI  - Isometric exercises reduce temporal summation of pressure pain in humans.
AB  - BACKGROUND: Aerobic and isometric exercises are known to decrease pain
      sensitivity. The effect of different types of exercise on central mechanisms such
      as temporal summation of pain (TSP) is less clear. This study hypothesized that
      both aerobic and isometric exercises would increase pressure pain tolerance (PTT)
      and reduce TSP with greater effects after higher-intensity exercises. METHODS:
      One hundred thirty-six healthy subjects (18-65 years; 68 women) participated in
      two randomized crossover experiments with trials on two different days. PTT and
      TSP were assessed before and after bicycling and a non-exercise condition
      (experiment 1), and after low- and high-intensity bicycling and low- and high
      intensity isometric arm and leg exercises with the dominant arm/leg (experiment
      2). PTT and TSP were assessed before and after each exercise condition on the non
      dominant arm and leg by computer-controlled cuff algometry. TSP was assessed by
      visual analogue scale (VAS) scores of the pain intensity during sequential cuff
      pressure stimulation at the pain tolerance intensity related to that specific
      time point. RESULTS: In experiment 1, bicycling, but not the non-exercise
      condition, slightly increased PTT when assessed at the leg (p < 0.05). In
      experiment 2, isometric arm and leg exercises increased PTT and reduced VAS
      scores to sequential stimulation at the arm and leg (p < 0.05). No systematic
      difference was found between low- and high-intensity exercises. CONCLUSIONS:
      Different manifestations of hypoalgesia between aerobic and isometric exercises
      were found. Isometric exercises reduced temporal summation illustrating the
      potential for exercise as a rehabilitation procedure also targeting the central
      mechanisms.

PMID- 25371065
TI  - A long-term study examining the antibacterial effectiveness of Agion silver
      zeolite technology on door handles within a college campus.
AB  - Laboratory studies have shown that small concentrations of silver are effective
      at inhibiting the growth micro-organisms through the disruption of important cell
      structures and processes. The additional ability to incorporate silver into
      surfaces has increased the usage of silver in the medical field and expanded its
      use into the consumer market. To understand the impact of increased silver
      containing antimicrobial use, it is important to determine whether silver-based
      consumer goods are effective at reducing bacterial populations. Our study
      examined the antibacterial effectiveness of Agion silver zeolite technology
      applied to 25 silver- and control-coated door handles across a college campus.
      Door handles were sampled for 6 week periods in both the fall and spring
      semester, and bacteria were cultured and enumerated on tryptic soy agar (TSA),
      MacConkey agar (MAC) and mannitol salt agar (MSA). A significant difference was
      observed between the bacterial populations isolated from silver- and control
      coated door handles after 3 years. However, bacteria were consistently isolated
      from silver-coated door handles suggesting that the silver zeolite was only
      effective against a portion of the bacterial populations, and further studies are
      necessary to determine the identities of the isolated bacteria and the prevalence
      of silver resistance.

PMID- 25371066
TI  - DPPIV (CD26) as a novel stem cell marker in Ph+ chronic myeloid leukaemia.
AB  - The concept of leukaemic stem cells (LSCs) has been developed to explain the
      complex cellular hierarchy and biology of leukaemias and to screen for pivotal
      targets that can be employed to improve drug therapies through LSC eradication in
      these patients. Some of the newly discovered LSC markers seem to be expressed in
      a disease-specific manner and may thus serve as major research tools and
      diagnostic parameters. A useful LSC marker in chronic myeloid leukaemia (CML)
      appears to be CD26, also known as dipeptidylpeptidase IV. Expression of CD26 is
      largely restricted to CD34(+) /CD38(-) LSCs in BCR/ABL1(+) CML, but is not found
      on LSCs in other myeloid or lymphoid neoplasms, with the exception of lymphoid
      blast crisis of CML, BCR/ABL1p210 + acute lymphoblastic leukaemia, and a very few
      cases of acute myeloid leukaemia. Moreover, CD26 usually is not expressed on
      normal bone marrow (BM) stem cells. Functionally, CD26 is a cytokine-targeting
      surface enzyme that may facilitate the mobilization of LSCs from the BM niche. In
      this article, we review our current knowledge about the biology and function of
      CD26 on CML LSCs and discuss the diagnostic potential of this new LSC marker in
      clinical haematology. 

PMID- 25371067
TI  - Emerging roles for folate and related B-vitamins in brain health across the
      lifecycle.
AB  - Nutrition plays a fundamental role in supporting the structural and functional
      development of the human brain from conception, throughout early infancy and
      extending into later life. A growing body of evidence suggests that folate and
      the metabolically related B-vitamins are essential for brain health across all
      age groups, owing to their specific roles in C1 metabolism and particularly in
      the production of S-adenosylmethionine, a universal methyl donor essential for
      the production of neurotransmitters. Emerging, though not entirely consistent,
      evidence suggests that maternal folate status throughout pregnancy may influence
      neurodevelopment and behaviour of the offspring. Furthermore optimal B-vitamin
      status is associated with better cognitive health in ageing. Of note, a recent
      clinical trial provided evidence that supplementation with folic acid and related
      B-vitamins over a 2-year-period reduced global and regional brain atrophy, as
      measured by MRI scan in older adults. In terms of potential mechanisms, the
      effects of these B-vitamins on cognitive health may be independent or may be
      mediated by nutrient-nutrient and/or relevant gene-nutrient interactions.
      Furthermore, a new area of research suggests that the in utero environment
      influences health in later life. Folate, an important cofactor in C1 metabolism,
      is indirectly involved in DNA methylation, which in turn is considered to be one
      of the epigenetic mechanisms that may underlie fetal programming and brain
      development. The present review will explore the evidence that supports a role
      for folate and the related B-vitamins in brain health across the lifecycle, and
      potential mechanisms to explain such effects. 

PMID- 25371068
TI  - Cardiomyopathy in murine models of systemic sclerosis.
AB  - OBJECTIVE: Cardiomyopathy has emerged as a leading cause of death in patients
      with systemic sclerosis (SSc). However, the pathogenesis of SSc-related
      cardiomyopathy is poorly understood, and new therapies as well as platforms for
      testing are needed. The aim of this study was to characterize the histopathologic
      features of cardiomyopathy in patients with SSc and in common mouse models of
      SSc. METHODS: The histopathologic features of myocardial tissue specimens
      obtained at autopsy from 5 subjects with SSc and 5 control subjects matched for
      sex, age, and cardiovascular risk factors were evaluated and compared with those
      of myocardial tissue specimens obtained from 3 common mouse models of SSc with
      systemic manifestations: Fra-2-transgenic mice, mice with sclerodermatous chronic
      graft-versus-host disease (GVHD), and TSK-1 mice. RESULTS: Myocardial tissue from
      autopsy subjects with SSc and no clinically manifest cardiac involvement showed
      endothelial cell apoptosis with reduced capillary density, perivascular
      inflammation, myofibroblast differentiation, and accumulation of collagen. Only
      selected features of SSc-related cardiomyopathy were observed in the mice with
      chronic GVHD and TSK-1 mice. However, the myocardial tissue of Fra-2-transgenic
      mice mimicked all features of SSc-related cardiomyopathy and also demonstrated
      comparable vascular, inflammatory, and fibrotic manifestations. Of note, the
      expression of Fra-2 was also increased in the myocardium of autopsy subjects with
      SSc. CONCLUSION: We demonstrate that all typical manifestations of SSc-related
      cardiomyopathy are mimicked in Fra-2-transgenic mice. Moreover, overexpression of
      Fra-2 in the myocardium of autopsy subjects with SSc may suggest similar
      underlying pathogenic mechanisms. Thus, Fra-2-transgenic mice might be a suitable
      preclinical model with which to study the mechanisms of and therapeutic
      approaches to myocardial involvement in SSc.

PMID- 25371069
TI  - Activating transcription factor 3 interferes with p21 activation in histone
      deacetylase inhibitor-induced growth inhibition of epidermoid carcinoma cells.
AB  - Inhibition of histone deacetylase (HDAC) activity by HDAC inhibitors (HDACis)
      results in cancer cell growth inhibition, and HDACis have been revealed as
      potential anti-skin cancer agents. p21 is a cyclin-dependent kinase inhibitor and
      an essential regulator of growth inhibition. Recently, we reported that
      activating transcription factor 3 (ATF3) could significantly promote skin cancer
      cell growth. This study explored the relationship between ATF3 and HDACi-induced
      growth inhibition of epidermoid carcinoma cells. We found that trichostatin A
      (TSA) treatment inhibited cell growth in A431 epidermoid carcinoma cells in a
      dose-dependent manner. Simultaneously, p21 and ATF3 expression levels were
      upregulated and downregulated upon TSA stimulation, respectively. ATF3
      overexpression promoted cell growth and downregulated p21 expression. In
      contrast, ATF3 depletion resulted in cell growth reduction and p21
      transcriptional upregulation. More importantly, ATF3 overexpression partially
      antagonized TSA-induced growth inhibition and p21 activation. Collectively, these
      data demonstrate that ATF3 acts as an essential negative regulator of TSA-induced
      cell growth inhibition through interfering with TSA-induced p21 activation. 

PMID- 25371070
TI  - Combinatorial immunotherapy of sorafenib and blockade of programmed death-ligand
      1 induces effective natural killer cell responses against hepatocellular
      carcinoma.
AB  - Sorafenib, a multi-tyrosine kinase inhibitor, is a standard treatment for
      advanced hepatocellular carcinoma (HCC). Herein, we report that the combinatorial
      therapy of sorafenib and anti-programmed death-ligand 1 (PD-L1) monoclonal
      antibody (mAb) can be implemented with good results for HCC. Cancer mouse models
      were used to evaluate therapeutic efficacy and examine the immunologic mechanisms
      of the sorafenib/anti-PD-L1 mAb therapy. The combined administration of sorafenib
      and anti-PD-L1 mAb into tumor-bearing mice generated potent immune responses
      resulting in the complete eradication or remarkable reduction of tumor growth. In
      some instances, the sorafenib/anti-PD-L1 mAb therapy induced long-lasting
      protection against tumor rechallenges. The results indicate that NK cells but not
      CD4T cells or CD8 cells mediated the therapeutic efficacy of this combinatorial
      therapy. The overall results suggest that immunotherapy consisting of the
      combination of sorafenib/anti-PD-L1 mAb could be a promising new approach for
      treating patients with HCC. 

PMID- 25371071
TI  - Matrine inhibits the growth and induces apoptosis of osteosarcoma cells in vitro
      by inactivating the Akt pathway.
AB  - Matrine, a natural product, has been demonstrated to be a promising
      chemotherapeutic drug for some cancers. Using flow cytometric analysis of the
      cell cycle and apoptosis, we found that matrine inhibited the proliferation and
      induced apoptosis in the human osteosarcoma (OS) cell lines MG63, HOS, U2OS, and
      SAOS2 in vitro in a dose-dependent manner. We therefore assessed the role of the
      serine/threonine kinase Akt in the regulation of matrine-mediated cell growth
      inhibition and apoptosis induction in human OS cell lines. After treatment for 48
      h, matrine induced G0/G1-stage cell cycle arrest in MG63, U2OS, and SAOS2 cells
      associated with an increase in the expression of p27(Kip1) and a decrease in the
      expression of Akt, glycogen synthase kinase 3 (GSK3)-beta (Ser9), and cyclin D1.
      Furthermore, the pro-apoptotic factor Bax was upregulated. Overall, our findings
      suggest that matrine may be an effective anti-osteosarcoma drug due to its
      ability to inhibit proliferation and induce apoptosis in OS cells, possibly
      through the involvement of Akt signaling.

PMID- 25371074
TI  - Biglycan up-regulated vascular endothelial growth factor (VEGF) expression and
      promoted angiogenesis in colon cancer.
AB  - Biglycan is an important component of the extracellular matrix, which belongs to
      the small leucine-rich proteoglycan family. Recent studies have shown that
      biglycan expression is elevated in many tumor tissues and implies poor prognosis,
      such as colon cancer. However, the molecular mechanism of biglycan in colon
      cancer has not been investigated. The present study aimed to investigate the
      effects of biglycan on vascular endothelial growth factor (VEGF) expression in
      colon cancer cells and on tumor angiogenesis in vivo. Biglycan overexpression
      vectors were constructed, and the stable biglycan overexpression in human colon
      cancer cell lines (HCT116 cells) was established by G418 screening. The stable
      cell clones were subsequently used to initiate tumor xenografts in nude mice. Our
      results showed that biglycan overexpression notably up-regulated the levels of
      VEGF in colon cancer cells, which was further confirmed by immunohistochemistry
      analysis in the xenograft colon tumors. Moreover, high levels of biglycan
      promoted angiogenesis and colon tumor growth, as evidenced by the increased cell
      viability, colon tumor size, and weight, as well as the CD34 expression.
      Additionally, we found that the extracellular signal-regulated kinase (ERK)
      signaling pathway was activated by biglycan in colon cancer cells. The ERK
      inhibitor PD98059 dramatically reversed the increased expression of VEGF induced
      by biglycan. Taken together, our results indicated that biglycan up-regulated
      VEGF expression in colon cancer cells and promoted tumor angiogenesis. Biglycan
      mediated VEGF regulation may correlate with the activation of the ERK signaling
      pathway. Therefore, biglycan may be a promising target for anti-angiogenic
      therapy for cancer. 

PMID- 25371075
TI  - Multidirectional walk test in individuals with Parkinson's disease: a validity
      study.
AB  - Gait parameters of forward, backward, and sideways walk were studied when the
      participants walked overground in four directions at their self-selected speed
      and were compared with walking in the four directions on an instrumented GAITRite
      walkway. Intraclass correlation coefficients between the overground walk test
      measures and the instrumented walkway measures of gait speed, cadence, and stride
      length for the forward walk were 0.85, 0.88, and 0.87, respectively. For the
      backward walk, the coefficients were 0.91 for gait speed, 0.75 for cadence, and
      0.93 for stride length. For the sideways walk, the coefficients were 0.92 for
      gait speed, 0.93 for cadence, and 0.94 for stride length. Gait parameters of
      forward, backward, and sideways walk obtained by the overground walk test had
      excellent agreement with those obtained by the instrumented walkway. The quick
      timed test provided quantitative data for gait evaluation and was valid for
      clinical use. 

PMID- 25371072
TI  - Curcumin: a unique antioxidant offers a multimechanistic approach for management
      of hepatocellular carcinoma in rat model.
AB  - This study was designed to investigate the role of curcumin against
      hepatocellular carcinoma (HCC) induced in rats. Forty rats were divided into five
      groups. Group (1) was negative control. Groups (2), (4), and (5) were orally
      administrated N-nitrosodiethylamine for HCC induction, then group (2) was left
      untreated, and group (4) was treated orally with curcumin, while group (5) was
      intraperitoneally injected with doxorubicin. Group (3) was served as curcumin
      control group. Serum alpha-fetoprotein, alpha L-fucosidase and vascular
      endothelial growth factor levels were analyzed. Gamma glutamyl transferase (GGT)
      and heat shock protein gp96 (HSPgp96) gene expressions were detected by RT-PCR.
      The immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) and
      Ki-67 expressions was performed. Apoptosis was detected using DNA fragmentation
      assay. Also, histological investigation of liver tissue was achieved. Untreated
      HCC group showed significant elevation in the studied biochemical markers and
      significant upregulation in GGT and HSPgp96 gene expression as well as marked
      increase in PCNA and Ki-67 expression. Furthermore, this group revealed no DNA
      fragmentation. Histological investigation of liver tissue sections in HCC group
      revealed a typical anaplasia. On the other hand, the curcumin-treated group
      showed a significant depletion in the studied tumor markers and a significant
      downregulation in GGT and HSPgp96 gene expression. Also, this group displayed
      remarkable decrease in PCNA and Ki-67 expression. Moreover, this group revealed
      an obvious DNA fragmentation. Interestingly, treatment with curcumin showed
      remarkable improvement in the histological features of liver tissue. This study
      revealed the promising therapeutic role of curcumin against hepatocellular
      carcinoma owing to its antiangiogenic, antiproliferative, and apoptotic effects. 

PMID- 25371073
TI  - MicroRNA-93 suppress colorectal cancer development via Wnt/beta-catenin pathway
      downregulating.
AB  - MicroRNA-93 (miR-93) is involved in several carcinoma progressions. It has been
      reported that miR-93 acts as a promoter or suppressor in different tumors.
      However, till now, the role of miR-93 in colon cancer is unclear. Herein, we have
      found that expression of miR-93 was lower in human colon cancer tissue and
      colorectal carcinoma cell lines compared with normal colon mucosa. Forced
      expression of miR-93 in colon cancer cells inhibits colon cancer invasion,
      migration, and proliferation. Furthermore, miR-93 may downregulate the Wnt/beta
      catenin pathway, which was confirmed by measuring the expression level of the
      beta-catenin, axin, c-Myc, and cyclin-D1 in this pathway. Mothers against
      decapentaplegic homolog 7 (Smad7), as an essential molecular protein for nuclear
      accumulation of beta-catenin in the canonical Wnt signaling pathway, is predicted
      as a putative target gene of miR-93 by the silico method and demonstrated that it
      may be suppressed by targeting its 3'UTR. These findings showed that miR-93
      suppresses colorectal cancer development via downregulating Wnt/beta-catenin, at
      least in part, by targeting Smad7. This study revealed that miR-93 is an
      important negative regulator in colon cancer and suggested that miR-93 may serve
      as a novel therapeutic agent that offers benefits for colon cancer treatment. 

PMID- 25371076
TI  - Nodal staging in lung cancer: a risk stratification model for lymph nodes
      classified as negative by EBUS-TBNA.
AB  - BACKGROUND: Over the last 10 years, endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) has become established as the first
      line nodal staging procedure of choice for lung cancer patients. However, the
      pathway for patients following a negative EBUS-TBNA has not been clearly defined.
      The primary aim of this study was to develop and validate a risk stratification
      model to categorize lymph nodes deemed negative by EBUS-TBNA into "low-risk" and
      "high-risk" groups, where "risk" refers to the risk of false negative sampling.
      METHODS: A retrospective analysis of a prospectively maintained database at a UK
      tertiary EBUS-TBNA centre was performed. Only patients with primary lung cancer
      and only negative lymph nodes by EBUS-TBNA were included in the analysis. A risk
      stratification model was built from a derivation set using independent predictors
      of malignancy and the validation set used to evaluate the constructed model. The
      study period was from March 2010 to August 2013. RESULTS: Three hundred twenty
      nine lymph nodes were included in the analysis (derivation set n = 196,
      validation set n = 133). Lymph node standardized uptake value, the standardized
      uptake value ratio between the lymph node and primary tumor, and heterogeneous
      echogenicity during sonographic assessment were the only independent predictors
      of malignancy. Using a simplified scoring system based on the natural logs of the
      odds ratios from the multivariable analysis on the derivation sample, lymph nodes
      can be stratified into low risk (score <=1) and high risk (score >=2). One
      hundred forty-one of 142 and 94 of 96 lymph nodes classified as low risk in the
      derivation and validation set, respectively, were ultimately proven to be benign
      and 35 of 54 and 24 of 37 lymph nodes classified as high risk were proven
      malignant. The negative predictive value of the risk stratification model for the
      derivation set and validation set was 99.3% (95% confidence interval 96.1%-99.6%)
      and 97.9% (95% confidence interval 92%-99.6%), respectively. CONCLUSION: This
      risk stratification model may assist lung cancer multidisciplinary teams in
      deciding which patients need further staging procedures and which may proceed
      directly to treatment after a negative EBUS.

PMID- 25371078
TI  - Role of comorbidity on survival after radiotherapy and chemotherapy for
      nonsurgically treated lung cancer.
AB  - BACKGROUND: Comorbidity, such as diseases of the cardiovascular, pulmonary, and
      other systems, may influence prognosis in lung cancer and complicate its
      treatment. The performance status of patients, which is a known prognostic
      marker, may also be influenced by comorbidity. Due to the close link between
      tobacco smoking and lung cancer, and because lung cancer is often diagnosed in
      advanced ages (median age at diagnosis in Denmark is 70 years), comorbidity is
      present in a large proportion of lung cancer patients. METHODS: Patients with any
      stage lung cancer who did not have surgical treatment were identified in the
      Danish Lung Cancer Registry. Danish Lung Cancer Registry collects data from
      clinical departments, the Danish Cancer Registry, Danish National Patient
      Registry, and the Central Population Register. A total of 20,552 patients
      diagnosed with lung cancer in 2005 to 2011 were identified. Comorbidity data were
      extracted from the Danish National Patient Registry, which is a register of all
      in- and outpatient visits to hospitals in Denmark. By record linkage, lung cancer
      patients who had previously been diagnosed with comorbid conditions were assigned
      a Charlson comorbidity index. Initial cancer treatment was categorized as
      chemotherapy, chemoradiation, radiotherapy, or no therapy. Data on Charlson
      comorbidity index, performance status, age, sex, stage, pulmonary function
      (forced expiratory volume in 1 second), histology, and type of initial treatment
      (if any) were included in univariable and multivariable Cox proportional hazard
      analyses. RESULTS: Treatment rates for chemotherapy and chemoradiation declined
      with increasing comorbidity and in particular increasing age. Women received
      treatment more often than men. In a univariable analysis of all patients
      combined, stage, performance status, age, sex, lung function, and comorbidity
      were all associated with survival. Apart from excess mortality among patients
      with unspecified histological subtypes (hazard ratio), there was no clear
      difference between the specified subtypes. When adjusting for the other factors,
      particularly age, sex, performance status, and stage proved to be robust while
      risk estimates for comorbidity were attenuated somewhat. When grouped by the
      three types of cancer treatment or no treatment, there was no influence of
      comorbidity on radiation therapy and modest influence on survival after
      chemotherapy and chemoradiation. In contrast, age remained a strong negative
      prognosticator after multivariate adjustment as did stage and performance status.
      CONCLUSION: Comorbidity has a limited effect on survival and only for patients
      treated with chemotherapy. It is rather the performance of the patient at
      diagnosis than the medical history that prognosticates survival in this patient
      group.

PMID- 25371077
TI  - PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed +
      carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin +
      bevacizumab followed by maintenance bevacizumab in patients ith advanced
      nonsquamous non-small-cell lung cancer.
AB  - INTRODUCTION: PRONOUNCE compared the efficacy and safety of
      pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with
      paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in
      patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). METHODS:
      Patients >=18 years of age with stage IV nonsquamous NSCLC (American Joint
      Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance
      status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed,
      500 mg/m, carboplatin, area under the curve = 6) followed by Pem maintenance or
      Pac+Cb+Bev (paclitaxel, 200 mg/m, carboplatin, area under the curve = 6, and
      bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive
      disease or discontinuation. The primary objective was progression-free survival
      (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall
      survival (OS), overall response rate (ORR), disease control rate (DCR), and
      safety. Resource utilization was also assessed. RESULTS: Baseline characteristics
      of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well
      balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for
      Pac+Cb+Bev (hazard ratio = 0.85, 90% confidence interval, 0.7-1.04; p = 0.176);
      PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly
      more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia
      (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4
      neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and
      grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of
      hospitalizations and overall length of stay did not differ significantly between
      the arms. CONCLUSIONS: Pem+Cb did not produce significantly better G4PFS compared
      with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with
      Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles
      differed.

PMID- 25371079
TI  - Disparities in treatment of patients with inoperable stage I non-small cell lung
      cancer: a population-based analysis.
AB  - BACKGROUND: Patients unable to receive surgery for stage I non-small cell lung
      cancer (NSCLC) can undergo conventional radiotherapy (ConvRT), stereotactic body
      radiotherapy (SBRT), or no treatment (NoTx). This study assessed patterns of care
      and disparities in the receipt of each of these treatments. METHODS: The study
      included patients in the National Cancer Database from 2003 to 2011 with T1
      T2N0M0 inoperable lung cancer (n = 39,822). Logistic regressions were performed
      to determine predictors of receiving any radiation versus NoTx and for receiving
      SBRT versus ConvRT. RESULTS: Treatment with radiation was significantly less
      likely in blacks (odds ratio, OR 0.65) and Hispanics (OR 0.42) compared with
      whites. Treatment with SBRT versus ConvRT was more likely in an academic research
      program (OR 2.62) and a high-volume facility (OR 7.00) compared with community
      cancer programs or low-volume facilities. In 2011, use of SBRT, ConvRT, and NoTx
      was 25%, 28%, and 46% for patients in a community cancer center versus 68%, 11%,
      and 21%, respectively, in an academic center (p < 0.0001). CONCLUSION: There were
      marked institutional and socioeconomic variations in the treatment of inoperable
      stage I NSCLC. These results suggest that removal of barriers to receive
      radiation therapy and particularly improved access to SBRT may meaningfully
      improve survival in this disease.

PMID- 25371080
TI  - Atypical carcinoid tumor of the lung: a surveillance, epidemiology, and end
      results database analysis.
AB  - BACKGROUND: Atypical carcinoid (AC) of the lung is a rare form of thoracic
      malignancy. The limited knowledge of its biology and outcome stems largely from
      small, single institution experiences. We analyzed the Surveillance,
      Epidemiology, and End Results database (SEER) to better understand the clinical
      characteristics of this disease. METHODS: Demographic, treatment, and outcome
      data on all patients with pulmonary AC were obtained from the SEER database with
      18 reporting sites from 1973 to 2010 using SEER*Stat 8.1.2. Statistical analysis
      was performed using SAS 9.3 (SAS Institute, Inc., Cary, NC). RESULTS: There were
      947,463 patients diagnosed with lung and bronchus tumors in the SEER database, of
      which 441 had AC (0.05%). Median age of AC patients was 65 years; 69% were women
      and 87% of white ethnicity. Metastatic disease was present in 20% of patients at
      diagnosis. In terms of treatment, 78% of patients underwent resection and 12.5%
      received radiation. The overall 1-year and 3-year survival rates were 86% and
      67%, respectively. The 3-year survival rates for distant (M1), regional (lymph
      node involvement), and localized (lung only) disease were 26% (13 of 50), 69% (50
      of 72), and 85% (99 of 116), respectively. On univariate analysis, patients
      treated with surgery had reduced risk of death (hazard ratio, HR 0.19; p <
      0.001), whereas radiation treatment was associated with increased risk of death
      (HR 2.45; p < 0.001). CONCLUSIONS: AC accounted for less than 1% of all lung
      cancers diagnosed and was more frequent in women. The best outcomes were observed
      with surgical resection for localized disease.

PMID- 25371081
TI  - Super-resolved fluorescence microscopy: Nobel Prize in Chemistry 2014 for Eric
      Betzig, Stefan Hell, and William E. Moerner.
AB  - A big honor for small objects: The Nobel Prize in Chemistry 2014 was jointly
      awarded to Eric Betzig, Stefan Hell, and William E. Moerner "for the development
      of super-resolved fluorescence microscopy". This Highlight describes how the
      field of super-resolution microscopy developed from the first detection of a
      single molecule in 1989 to the sophisticated techniques of today. 

PMID- 25371082
TI  - Interleukin-21 promotes the development of ulcerative colitis and regulates the
      proliferation and secretion of follicular T helper cells in the colitides
      microenvironment.
AB  - Patients with ulcerative colitis (UC) are at increased risk of developing colitis
      associated colon cancer. Previous studies have indicated that interleukin (IL)
      21, which is predominantly secreted by follicular T helper (Tfh) cells, is
      overproduced in inflammatory bowel diseases. In order to investigate the role of
      IL-21 in UC and the association between IL-21 and Tfh cells, the number of Tfh
      cells and the level of IL-21 were investigated in colonic tissues from UC
      patients and wild-type (WT) mice, which were induced by dextran sulphate sodium
      (DSS). High Tfh cell counts and levels of IL-21 were observed in UC patients and
      WT mice with DSS-induced colitis. Subsequent comparison of the mucosal damage and
      expression of Tfh-associated cytokines in the WT mice and IL-21 knockout (IL
      21KO) mice following DSS administration, revealed that IL-21KO mice were largely
      protected against colitis and exhibited reduced infiltration of Tfh cells, as
      well as decreased production of Tfh-associated cytokines. The present study also
      found that IL-21 was necessary for the proliferation and secretion of Tfh cells
      in vitro. In addition, neutralization of IL-21 in DSS-administered WT mice using
      anti-IL-21 reduced the number of Tfh cells and the level of mucosal damage.
      Administration of a neutralizing IL-21 antibody decreased the colonic
      infiltration of Tfh cells and reduced damage to the mucosa. These results
      indicated that Tfh cells are important in UC and that its effector molecule, IL
      21, is not only a critical regulator of inflammation, but also regulates the
      proliferation and response of Tfh cells in the colitis microenvironment.

PMID- 25371083
TI  - Service, training, mentorship: first report of an innovative education-support
      program to revitalize primary care social service in Chiapas, Mexico.
AB  - BACKGROUND: The Mexican mandatory year of social service following medical
      school, or pasantia, is designed to provide a safety net for the underserved.
      However, social service physicians (pasantes) are typically unpracticed,
      unsupervised, and unsupported. Significant demotivation, absenteeism, and
      underperformance typically plague the social service year. OBJECTIVE: Companeros
      en Salud (CES) aimed to create an education-support package to turn the pasantia
      into a transformative learning experience. DESIGN: CES recruited pasantes to
      complete their pasantia in CES-supported Ministry of Health clinics in rural
      Chiapas. The program aims to: 1) train pasantes to more effectively deliver
      primary care, 2) expose pasantes to central concepts of global health and social
      medicine, and 3) foster career development of pasantes. Program components
      include supportive supervision, on-site mentorship, clinical information
      resources, monthly interactive seminars, and improved clinic function. We report
      quantitative and qualitative pasante survey data collected from February 2012 to
      August 2013 to discuss strengths and weaknesses of this program and its
      implications for the pasante workforce in Mexico. RESULTS: Pasantes reported that
      their medical knowledge, and clinical and leadership skills all improved during
      the CES education-support program. Most pasantes felt the program had an overall
      positive effect on their career goals and plans, although their self-report of
      preparedness for the Mexican residency entrance exam (ENARM) decreased during the
      social service year. One hundred percent reported they were satisfied with the
      CES-supported pasantia experience and wished to help the poor and underserved in
      their careers. CONCLUSIONS: Education-support programs similar to the CES program
      may encourage graduating medical students to complete their social service in
      underserved areas, improve the quality of care provided by pasantes, and address
      many of the known shortcomings of the pasantia. Additional efforts should focus
      on developing a strategy to expand this education-support model so that more
      pasantes throughout Mexico can experience a transformative, career-building,
      social service year.

PMID- 25371084
TI  - S100 expression by atypical megakaryocytes: a previously unreported potential
      pitfall in dermatopathology.
AB  - Several types of large atypical epithelioid cells can mimic tumoral melanocytes
      and can therefore be a source of misdiagnosis of melanoma. Megakaryocytes are one
      of these types, and are not frequently mentioned in the literature. In the
      current report, we present the case of a 76-year-old man presenting with acute
      panmyelosis with myelofibrosis. The bone marrow biopsy contained atypical
      megakaryocytes that expressed S100 in the cytoplasm. We discuss how such aberrant
      expression could be a source of some diagnostic problems in dermatopathology,
      including cutaneous melanoma, metastasis of melanoma in bone marrow and
      metastasis of melanoma in sentinel lymph nodes. 

PMID- 25371085
TI  - Mean platelet volume may not be useful as a marker for prediction of preterm
      premature rupture of membranes.

PMID- 25371086
TI  - CT-guided radiofrequency ablation of osteoid osteoma using a novel battery
      powered drill.
AB  - OBJECTIVE: To evaluate the use of a novel battery-powered drill, enabling
      specimen requirement while drilling, in radiofrequency ablation of osteoid
      osteoma as an alternative to conventional orthopedic drills. MATERIALS AND
      METHODS: Between 2009 and 2013, altogether 33 patients underwent CT-guided
      radiofrequency ablation of an osteoid osteoma at our institution. To access the
      nidus of the clinically and radiologically suspected osteoid osteoma, a channel
      was drilled using the OnControl Bone Marrow Biopsy System (OBM, Arrow OnControl,
      Teleflex, Shavano Park, TX, USA) and a biopsy was taken. Procedure time (i.e.,
      drilling including local anesthesia), amount of scans (i.e., single-shot
      fluoroscopy), radiation exposure, and the results of biopsy were investigated and
      compared retrospectively to a classical approach using either a manual bone
      biopsy system or a conventional orthopedic drill (n = 10) after ethical review
      board approval. RESULTS: Drilling the tract into the nidus was performed without
      problems in 22 of the 23 OBM cases. Median procedure time was 7 min compared to
      13 min using the classical approach (p < 0.001). Median amount CT scans,
      performed to control correct positioning of the drill was comparable with 26
      compared to 24.5 (p = NS) scans. Histologically, the diagnosis of osteoid
      osteomas could be determined in all 17 cases where a biopsy was taken.
      Radiofrequency ablation could be performed without problems in any case.
      CONCLUSIONS: The use of the battery-powered drill was feasible and facilitated
      the access to the osteoid osteoma's nidus offering the possibility to extract a
      specimen in the same step.

PMID- 25371088
TI  - Cervical laminoplasty.

PMID- 25371087
TI  - Pelvic morphology in ischiofemoral impingement.
AB  - OBJECTIVE: To assess MRI measures to quantify pelvic morphology that may
      predispose to ischiofemoral impingement (IFI). We hypothesized that patients with
      IFI have a wider interischial distance and an increased femoral neck angle
      compared with normal controls. MATERIALS AND METHODS: The study was IRB-approved
      and complied with HIPAA guidelines. IFI was diagnosed based on clinical findings
      (hip or buttock pain) and ipsilateral edema of the quadratus femoris muscle on
      MRI. Control subjects did not report isolated hip/buttock pain and underwent MRI
      for surveillance of neoplasms or to exclude pelvic fractures. Two MSK
      radiologists measured the ischiofemoral (IF) and quadratus femoris (QF) distance,
      the ischial angle as a measure of inter-ischial distance, and the femoral neck
      angle. The quadratus femoris muscle was evaluated for edema. Groups were compared
      using ANOVA. Multivariate standard least-squares regression modeling was used to
      control for age and gender. RESULTS: The study group comprised 84 patients with
      IFI (53 +/- 16 years, 73 female, 11 male) and 51 controls (52 +/- 16 years, 33
      female, 18 male). Thirteen out of 84 patients (15%) had bilateral IFI. Patients
      with IFI had decreased IF and QF distance (p < 0.0001), increased ischial angle
      (p = 0.004), and increased femoral neck angle (p = 0.02) compared with controls,
      independent of age and gender. CONCLUSION: Patients with IFI have increased
      ischial and femoral neck angles compared with controls. These anatomical
      variations in pelvic morphology may predispose to IFI. MRI is a useful method of
      not only assessing the osseous and soft-tissue abnormalities associated with IFI,
      but also of quantifying anatomical variations in pelvic morphology that can
      predispose to IFI.

PMID- 25371089
TI  - Fusion in degenerative spondylolisthesis: comparison of osteoconductive and
      osteoinductive bone graft substitutes.
AB  - INTRODUCTION: The emergent widespread options of bone graft substitutes for
      spinal fusion procedures vary in their osteobiologic activity. A majority of
      current literature focuses on the comparison of osteoinductive (OI) or
      osteoconductive (OC) bone graft substitutes individually against ICBG. These
      studies have demonstrated the legitimacy of bone graft substitutes, but despite
      the widespread use in spinal fusion procedures there is a dearth in the current
      literature in the direct comparison of OC and OI substitutes. This retrospective
      comparative analysis compares the efficacy of OI vs. solely OC agents in
      producing radiographic fusion on patients with DS. METHODS: Patients, who
      underwent a lumbar fusion for DS with at least 6 months post-op radiographs, were
      divided based on whether they received an OC or OI bone graft substitute. The OC
      groups included allografts, calcium phosphate, ceramics and hydroxyapatite
      products. The OI group included bone morphogenic protein, demineralized bone
      matrix, and stem cell-based products. MEASUREMENT CRITERIA: Using a conservative
      hierarchical approach to determine fusion, fusion criteria included stringent use
      of multiple measurement methods including flexion/extension x-rays, Lenke and
      Brantigan CT fusion measurement criteria, and history of revision surgery due to
      pseudoarthrosis. RESULTS: A total of 126 patients (78 OI, 48 OC) met the studies
      inclusion criteria for the assessment for fusion. The mean time for flexion
      extension radiographic evaluation was 13.1 months for the OI group and 15 months
      for the OC group. The mean time for CT scan evaluation was 18 months for the OI
      group and 15.9 months for the OC group. Using the stated hierarchical criteria
      for fusion stated above, the fusion rate for the OI group was 87.18%, and the
      fusion rate for the OC group was 93.75%. The difference in OI and OC groups was
      not statistically significant (P = 0.367). Based on the demographic data
      collected, there were no statistically significant factors determining fusion.
      CONCLUSION: With the vastly growing market for OI and OC materials commonly used
      in lumbar spinal fusions, the options for surgical treatment for degenerative
      spondylolisthesis are ever expanding. No significant difference was found when
      comparing fusion rates between the two types of materials in this retrospective
      analysis. Interestingly, TLIF procedures provided lower fusion rates than
      posterolateral fusion procedures. This may be due to a small sample size but the
      association with a minimally invasive technique warrants investigation. Due to
      the substantial difference in price between the OI and OC materials and the lack
      of evidence supporting higher fusion rates with more expensive OI agents, it is
      incumbent on the spine community to consider and reassess the products that are
      routinely used.

PMID- 25371090
TI  - Endosomes: guardians against [Ru(Phen)3]2+ photo-action in endothelial cells
      during in vivo pO2 detection?
AB  - Phototoxicity is a side-effect of in vitro and in vivo oxygen partial pressure
      (pO2) detection by luminescence lifetime measurement methods. Dichlorotris(1,10
      phenanthroline)-ruthenium(ii) hydrate ([Ru(Phen)3]2+) is a water soluble pO2
      probe associated with low phototoxicity, which we investigated in vivo in the
      chick's chorioallantoic membrane (CAM) after intravenous or topical
      administration and in vitro in normal human coronary artery endothelial cells
      (HCAEC). In vivo, the level of intravenously injected [Ru(Phen)3]2+ decreases
      within several minutes, whereas the maximum of its biodistribution is observed
      during the first 2 h after topical application. Both routes are followed by
      convergence to almost identical "intra/extra-vascular" levels of [Ru(Phen)3]2+.
      In vitro, we observed that [Ru(Phen)3]2+ enters cells via endocytosis and is then
      redistributed. None of the studied conditions induced modification of lysosomal
      or mitochondrial membranes without illumination. No nuclear accumulation was
      observed. Without illumination [Ru(Phen)3]2+ induces changes in endoplasmic
      reticulum (ER)-to-Golgi transport. The phototoxic effect of [Ru(Phen)3]2+ leads
      to more marked ultrastructural changes than administration of [Ru(Phen)3]2+ only
      (in the dark). These could lead to disruption of Ca2+ homeostasis accompanied by
      mitochondrial changes or to changes in secretory pathways. In conclusion, we have
      demonstrated that the intravenous injection of [Ru(Phen)3]2+ into the CAM model
      mostly leads to extracellular localization of [Ru(Phen)3]2+, while its topical
      application induces intracellular localization. We have shown in vivo that
      [Ru(Phen)3]2+ induces minimal photo-damage after illumination with light doses
      larger by two orders of magnitude than those used for pO2 measurements. This low
      phototoxicity is due to the fact that [Ru(Phen)3]2+ enters endothelial cells via
      endocytosis and is then redistributed towards peroxisomes and other endosomal and
      secretory vesicles before it is eliminated via exocytosis. Cellular response to
      [Ru(Phen)3]2+, survival or death, depends on its intracellular concentration and
      oxidation-reduction properties.

PMID- 25371092
TI  - Neutralizing antibodies respond to a bivalent dengue DNA vaccine or/and a
      recombinant bivalent antigen.
AB  - There is currently no effective vaccine to prevent dengue infection, despite the
      existence of multiple studies on potential methods of immunization. The aim of
      the present study was to explore the effect of DNA and/or recombinant protein on
      levels of neutralizing antibodies. For this purpose, envelope domain IIIs of
      dengue serotypes 1 and 2 (DEN-1/2)were spliced by a linker (Gly-Gly-Ser-Gly-Ser)3
      and cloned into the prokaryotic expression plasmid pET30a (+) and eukaryotic
      vector pcDNA3.1 (+). The chimeric bivalent protein was expressed in Escherichia
      coli, and one-step purification by high-performance liquid chromatography was
      conducted. Protein expression levels of the DNA plasmid were tested in BHK-21
      cells by indirect immunofluorescent assay. In order to explore a more effective
      immunization strategy and to develop neutralizing antibodies against the two
      serotypes, mice were inoculated with recombinant bivalent protein, the DNA
      vaccine, or the two given simultaneously. Presence of the specific antibodies was
      tested by ELISA and the presence of the neutralizing antibodies was determined by
      plaque reduction neutralization test. Results of the analysis indicated that the
      use of a combination of DNA and protein induced significantly higher titers of
      neutralizing antibodies against either DEN-1 or DEN-2 (1:64.0 and 1:76.1,
      respectively) compared with the DNA (1:24.7 and 1:26.9, DEN-1 and DEN-2,
      respectively) or the recombinant protein (1:34.9 and 1:45.3 in DEN-1 and DEN-2,
      respectively). The present study demonstrated that the combination of recombinant
      protein and DNA as an immunization strategy may be an effective method for the
      development of a vaccine to prevent dengue virus infection. 

PMID- 25371091
TI  - Susceptibility to particle health effects, miRNA and exosomes: rationale and
      study protocol of the SPHERE study.
AB  - BACKGROUND: Despite epidemiological findings showing increased air pollution
      related cardiovascular diseases (CVD), the knowledge of the involved molecular
      mechanisms remains moderate or weak. Particulate matter (PM) produces a local
      strong inflammatory reaction in the pulmonary environment but there is no final
      evidence that PM physically enters and deposits in blood vessels. Extracellular
      vesicles (EVs) and their miRNA cargo might be the ideal candidate to mediate the
      effects of PM, since they could be potentially produced by the respiratory
      system, reach the systemic circulation and lead to the development of
      cardiovascular effects.The SPHERE ("Susceptibility to Particle Health Effects,
      miRNAs and Exosomes") project was granted by ERC-2011-StG 282413, to examine
      possible molecular mechanisms underlying the effects of PM exposure in relation
      to health outcomes. METHODS/DESIGN: The study population will include 2000
      overweight (25 < BMI < 30 kg/cm2) or obese (BMI >= 30 kg/cm2) subjects presenting
      at the Center for Obesity and Work (Fondazione IRCCS Ca' Granda Ospedale Maggiore
      Policlinico, Milan, Italy).Each subject donates blood, urine and hair samples.
      Extensive epidemiological and clinical data are collected. Exposure to PM is
      assigned to each subject using both daily PM10 concentration series from air
      quality monitors and pollutant levels estimated by the FARM (Flexible air Quality
      Regional Model) modelling system and elaborated by the Regional Environmental
      Protection Agency.The recruitment period started in September 2010 and will
      continue until 2015. At December 31, 2013 we recruited 1250 subjects, of whom 87%
      lived in the province of Milan.Primary study outcomes include cardiometabolic and
      respiratory health effects. The main molecular mechanism we are investigating
      focuses on EV-associated microRNAs. DISCUSSION: SPHERE is the first large study
      aimed to explore EVs as a novel potential mechanism of how air pollution exposure
      acts in a highly susceptible population. The rigorous study design, the
      availability of banked biological samples and the potential to integrate
      epidemiological, clinical and molecular data will also furnish a powerful base
      for investigating different complementary molecular mechanisms. Our findings, if
      confirmed, could lead to the identification of potentially reversible alterations
      that might be considered as possible targets for new diagnostic and therapeutic
      interventions.

PMID- 25371093
TI  - Combining Coronary with Carotid and Cerebrovascular Angiography Using Prospective
      ECG Gating and Iterative Reconstruction with 256-slice CT.
AB  - OBJECTIVE: To investigate the image quality and radiation dose of combined
      coronary and carotid/cerebrovascular angiography with ECG gating and iterative
      reconstruction using 256-slice CT compared with the findings with the two
      examinations performed separately. PATIENTS AND METHODS: One hundred sixty-five
      consecutive patients underwent a single-injection single-pass combination of
      coronary and carotid/cerebrovascular CT angiography (group A), coronary CT
      angiography alone (group B), or carotid/cerebrovascular CT angiography alone
      (group C). We assessed the image quality of the combined and separate
      examinations and calculated the respective effective radiation doses. We
      evaluated the differences in the proportions of image quality grade between the
      combination and single-examination groups. Diagnostic performance of the combined
      scanning for detecting significant vascular stenosis has been compared with
      reference digital subtraction angiography (DSA) in the patient subgroup of group
      A. RESULTS: There was no significant difference in age, body mass index (BMI), or
      gender distribution among the 3 groups (all P > 0.05). But there was significant
      difference in scan length, DLP, and effective dose among the 3 groups (all P <
      0.05). There were no significant differences in the effective radiation dose of
      coronary scanning between groups A and B (P > 0.05), while the effective
      radiation dose of carotid/cerebrovascular scanning in group A was significantly
      lower than that in group C (P < 0.05), and the total effective radiation dose in
      group A were relatively low (2.21 +/- 1.38 mSv). The differences of the
      proportion of carotid/cerebrovascular image quality grades between groups A and C
      were not significant (P > 0.05). In a subgroup of group A of 30 patients with
      DSA, combined computed tomographic angiography successfully detected 56 coronary
      stenosis on per-segment basis, and 62 stenosis on carotid and cerebral artery.
      The sensitivity, specificity, positive and negative predictive value (NPV) of
      coronary stenosis were 91.80%, 95.60%, 87.50% and 97.21%, respectively. The
      sensitivity, specificity, positive and NPV of carotid/cerebrovascular stenosis
      were 93.55%, 94.68%, 92.06% and 95.70%, respectively. CONCLUSION: Combination of
      coronary and carotid/cerebrovascular angiography with 256-slice CT scanner with
      prospective ECG gating and iterative reconstruction produces diagnostic-quality
      images of the coronary, carotid, and cerebrovascular systems in a single
      examination, using less contrast medium and a lower radiation dose than when the
      two examinations are performed separately. This novel technique has high accuracy
      in detecting significant stenosis in one image setting.

PMID- 25371094
TI  - Constitutive activation of the renin-angiotensin system reduces visceral fat and
      improves glucose tolerance in mice.
AB  - INTRODUCTION: The renin-angiotensin system (RAS), and particularly angiotensin
      II, is involved in the control of energy balance, glucose homeostasis and kidney
      functions. The integrated impact of the RAS on glucose homeostasis is still a
      matter of debate. MATERIALS AND METHODS: We used a model of constitutive RAS
      activation in double transgenic mice (dTGM) carrying both human angiotensinogen
      and human renin genes. We evaluated energy balance, measured renal functions,
      performed glucose and insulin tolerance tests, and used ramipril to inhibit the
      angiotensin-converting enzyme. RESULTS: dTGM had a lower physical activity and an
      increased food intake without change in body weight. Renal impairment was
      characterized by low-grade albuminuria. High urinary output secondary to
      polydipsia was associated with proximal tubule dysfunction. Compared to controls,
      dTGM had a lower hyperglycemia induced by an intraperitoneal glucose
      administration. This decrease was not due to changes in insulin sensitivity
      and/or secretion. dTGM had an increased creatinine production and a lower
      epididymal fat mass. Acute inhibition of angiotensin-converting enzyme with
      ramipril did not suppress this improved glucose tolerance profile. CONCLUSION:
      Chronic RAS activation is not sufficient to cause insulin resistance in mice.
      Moreover, adaptation to constitutive RAS activation in mice results in a better
      glucose tolerance.

PMID- 25371095
TI  - The distinct distributions of immunocompetent cells in rat dentin pulp after
      pulpotomy.
AB  - Pulpotomy involves the removal of the coronal portion of pulp, including the
      diseased tissue, with the intent of maintaining the vitality of the remaining
      pulpal tissue via a therapeutic dressing. Once odontoblasts suffer injuries, the
      differentiation of mesenchymal cells is induced from the precursor cell
      population in the dental pulp, and these cells are recruited to the injured site
      to differentiate into odontoblasts. However, the involvement of immunocompetent
      cells during pulpal regeneration remains unclear. Thus, the purpose of this study
      was to investigate the properties of macrophages that infiltrated wound healing
      sites in rats between 1 and 28 days after pulpotomy (dap). During the
      inflammatory phase, ED1(+) (CD68(+) ) macrophages significantly increased
      throughout root pulp, especially apical to the demarcation zone, and this
      population persisted until 3 dap before decreasing gradually until 28 dap. OX6(+)
      macrophages expressing class II MHC also increased in the apical pulp at 1 dap
      and declined thereafter. However, OX6(+) cells appeared prior to dentin bridge
      formation at 3 dap and appeared again apical to the dentin bridge during the
      healing stage at 14 dap. The shift from ED1(+) cells in the inflammation phase to
      OX6(+) cells during dentin bridge formation might contribute to wound healing.

PMID- 25371096
TI  - Successful cardiac resuscitation with extracorporeal membrane oxygenation in the
      setting of persistent ventricular fibrillation: a case report.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) technology is a viable
      option for short-term support in the setting of acute cardiac ischemia. To
      supplement cardiopulmonary resuscitation (CPR) in select patients, ECMO is used
      successfully for witnessed in hospital cardiac arrest. In the setting of an acute
      myocardial infarction (MI), bridging to a revascularization procedure is
      important in improving overall survival. CASE PRESENTATION: We describe the first
      known case of a 56-year-old Caucasian male with an anterior ST elevation
      myocardial infarction (STEMI) who underwent percutaneous coronary intervention
      (PCI) in which the entire procedure was carried out with the patient being in
      persistent ventricular fibrillation (VF) resistant to defibrillation on ECMO
      support. Subsequent to revascularization, the patient's cardiac rhythm converted
      back to sinus rhythm with a single defibrillation shock with excellent neurologic
      recovery. CONCLUSION: Our case highlights the importance of early initiation of
      ECMO during PCI in achieving both improved cardiac and neurological outcomes
      during an acute coronary syndrome (ACS).

PMID- 25371097
TI  - Comparison of laparoscopic sigmoidectomy with and without preservation of the
      superior rectal artery: a single-institution retrospective study.
AB  - INTRODUCTION: The inferior mesenteric artery is usually divided during the
      resection of sigmoid colon cancers. However, this sometimes results in an
      insufficient blood supply to the anastomosis, leading to anastomotic leakage. We
      conducted a retrospective analysis to determine the feasibility and potential
      benefits of preserving the superior rectal artery (SRA). METHODS: Fifty-seven
      patients underwent SRA-preserving sigmoidectomy with D2 or D3 lymph node
      dissection (group A) between June 2008 and May 2012. These patients were compared
      with 35 patients who underwent sigmoidectomy without preservation of the SRA
      (group B) during the same period. RESULTS: The amount of blood loss, the number
      of harvested lymph nodes, and the postoperative morbidity rate did not differ
      significantly between the groups. There were no cases of anastomotic leakage in
      group A and there was one in group B, but this difference was not significant.
      The 3-year relapse-free survival rates also did not differ significantly between
      the two groups, irrespective of lymph node status. CONCLUSION: Sigmoidectomy with
      SRA preservation can be performed without compromising the quality of lymph node
      dissection and relapse-free survival. No advantage of preserving the SRA could be
      demonstrated, but it is noteworthy that no anastomotic leakage was noted among
      the 57 patients in group A.

PMID- 25371099
TI  - Incident light adjustable solar cell by periodic nanolens architecture.
AB  - Could nanostructures act as lenses to focus incident light for efficient
      utilization of photovoltaics? Is it possible, in order to avoid serious
      recombination loss, to realize periodic nanostructures in solar cells without
      direct etching in a light absorbing semiconductor? Here we propose and
      demonstrate a promising architecture to shape nanolenses on a planar
      semiconductor. Optically transparent and electrically conductive nanolenses
      simultaneously provide the optical benefit of modulating the incident light and
      the electrical advantage of supporting carrier transportation. A transparent
      indium-tin-oxide (ITO) nanolens was designed to focus the incident light-spectrum
      in focal lengths overlapping to a strong electric field region for high carrier
      collection efficiency. The ITO nanolens effectively broadens near-zero reflection
      and provides high tolerance to the incident light angles. We present a record
      high light-conversion efficiency of 16.0% for a periodic nanostructured Si solar
      cell. 

PMID- 25371098
TI  - Review: cancer-induced autoimmunity in the rheumatic diseases.

PMID- 25371101
TI  - Acute effects of different degrees of ultra-endurance exercise on systemic
      inflammatory responses.
AB  - BACKGROUND: Intense physical stress might promote inflammatory responses, whereas
      a regular physical exercise has positive influence. Little is known on the acute
      metabolic and inflammatory responses to different levels of strenuous exercise in
      trained athletes. AIM: To compare the short-term effect of two different ultra
      endurance competitions on the inflammatory profile in male triathletes. METHODS:
      We studied 14 Ironman (IR) and 13 Half Ironman (HIR) before and after their own
      specific race. We assessed body composition and measured blood cells, lipids,
      iron metabolism and plasma levels of some acute-phase cytokines and inflammatory
      markers. RESULTS: After the race, IR showed reduced total body water and fat-free
      mass, not related with the duration of exercise, and increased white cells and
      platelets; high-density lipoprotein levels also increased. IR, but not HIR,
      showed reduced iron levels, increased ferritin and transferrin, reduced %
      saturated transferrin. HIR showed higher basal interleukin (IL)-6, tumour
      necrosis factor (TNF)-alpha, IL-10, IL-1beta than IR; however, the post
      performance rise was greater in IR. Irisin increased only in HIR and osteocalcin
      decreased in IR. In the whole study group, delta of white blood cells was
      directly related with delta of monocyte chemoattractant protein 1, and Delta
      ferritin was inversely related with Deltaosteocalcin. CONCLUSIONS: A single ultra
      endurance competition induces an inflammatory response depending on the duration
      of physical effort, with increased acute-phase cytokines, and an altered iron
      metabolism. Irisin, whose biological meaning is still uncertain, seems to be
      associated with acute variations of some metabolic parameters.

PMID- 25371100
TI  - Keratocystic odontogenic tumor arising at the mandibular ramus with an impacted
      tooth: a case report and mimic lesions.
AB  - OBJECTIVES: To consider the biologic behaviors of keratocystic odontogenic tumors
      (KCOTs) and ameloblastomas and dentigerous cysts. METHODS: A 63-year-old Japanese
      man presented with swelling and discomfort in the left cheek during jaw movement.
      Examination revealed a multilocular lesion within the mandible extending from the
      left second premolar to the left mandibular ramus and coronoid process; the
      lesion contained a deviated impacted tooth. The tumor had expanded beyond the
      bone and was invading the masseter and medial pterygoid muscles. Marginal
      mandibulectomy with a free iliac bone graft was performed. RESULTS: No recurrence
      was observed during a 7-year follow-up. DISCUSSION: The histopathological
      diagnosis of the lesion showed it was a KCOT. These tumors usually grow within
      the bone, causing bone expansion. However, this tumor had expanded beyond the
      bone and invaded surrounding muscles. Thus, KCOTs can, in rare cases, manifest
      themselves as described here. Evaluating preoperative images and
      histopathological findings is important to determine the optimal treatment
      strategy.

PMID- 25371102
TI  - Surface patterns in drying films of silica colloidal dispersions.
AB  - We report an experimental study on the drying of silica colloidal dispersions.
      Here we focus on surface instability occurring in a drying paste phase before
      crack formation which affects the final film quality. Observations at macroscopic
      and microscopic scales reveal the occurrence of instability, and the morphology
      of the film surface. Furthermore, we show that the addition of adsorbing polymers
      on silica particles can be used to suppress the instability under particular
      conditions of molecular weight and concentration. We relate this suppression to
      the increase of the paste elastic modulus. 

PMID- 25371103
TI  - Evaluation of the internal construct validity of the Personal Care Participation
      Assessment and Resource Tool (PC-PART) using Rasch analysis.
AB  - BACKGROUND: The Personal Care Participation Assessment and Resource Tool (PC
      PART) is a 43-item, clinician-administered assessment, designed to identify
      patients' unmet needs (participation restrictions) in activities of daily living
      (ADL) required for community life. This information is important for identifying
      problems that need addressing to enable, for example, discharge from inpatient
      settings to community living. The objective of this study was to evaluate
      internal construct validity of the PC-PART using Rasch methods. METHODS: Fit to
      the Rasch model was evaluated for 41 PC-PART items, assessing threshold ordering,
      overall model fit, individual item fit, person fit, internal consistency,
      Differential Item Functioning (DIF), targeting of items and dimensionality. Data
      used in this research were taken from admission data from a randomised controlled
      trial conducted at two publically funded inpatient rehabilitation units in
      Melbourne, Australia, with 996 participants (63% women; mean age 74 years) and
      with various impairment types. RESULTS: PC-PART items assessed as one scale, and
      original PC-PART domains evaluated as separate scales, demonstrated poor fit to
      the Rasch model. Adequate fit to the Rasch model was achieved in two newly formed
      PC-PART scales: Self-Care (16 items) and Domestic Life (14 items). Both scales
      were unidimensional, had acceptable internal consistency (PSI =0.85, 0.76,
      respectively) and well-targeted items. CONCLUSIONS: Rasch analysis did not
      support conventional summation of all PC-PART item scores to create a total
      score. However, internal construct validity of the newly formed PC-PART scales,
      Self-Care and Domestic Life, was supported. Their Rasch-derived scores provided
      interval-level measurement enabling summation of scores to form a total score on
      each scale. These scales may assist clinicians, managers and researchers in
      rehabilitation settings to assess and measure changes in ADL participation
      restrictions relevant to community living. TRIAL REGISTRATION: Data used in this
      research were gathered during a registered randomised controlled trial:
      Australian and New Zealand Clinical Trials Registry ACTRN12609000973213. Ethics
      committee approval was gained for secondary analysis of data for this study.

PMID- 25371105
TI  - "In space" or "as space"?: a new model.
AB  - In this analysis natural systems are posed to subsystemize in a manner
      facilitating both structured information/energy sharing and an entropy
      maximization process projecting a three-dimensional, spatial, outcome. Numerical
      simulations were first carried out to determine whether n * n input-output
      matrices could, once entropy-maximized, project a three-dimensional Euclidean
      metric. Only 4 * 4 matrices could; a small proportion passed the test. Larger
      proportions passed when grouped random patterns on and within two- and three
      dimensional forms were tested. Topographical patterns within 31 stream basin
      systems in the state of Kentucky, USA, were then similarly investigated,
      anticipating that the spatial configuration of elevations within each basin would
      provide evidence of evolutionary control when interpreted as internal group
      relations. Twenty-eight of thirty-one of the systems pass the test unambiguously,
      with the remaining three approaching or reaching passage when sampling density is
      increased. Two measures of subsystem-level redundancies are also introduced;
      these show: (1) surprisingly, minimized internal redundancy levels at the four
      subsystems level of analysis of the stream systems (as opposed to the five or
      six, in contrast with the simulations), and (2) much lower average levels than
      those obtained in the simulations at the same dimensions, both suggesting a
      preferred evolutionary path under real world conditions. 

PMID- 25371106
TI  - Venus-Earth-Mars: comparative climatology and the search for life in the solar
      system.
AB  - Both Venus and Mars have captured the human imagination during the twentieth
      century as possible abodes of life. Venus had long enchanted humans-all the more
      so after astronomers realized it was shrouded in a mysterious cloak of clouds
      permanently hiding the surface from view. It was also the closest planet to
      Earth, with nearly the same size and surface gravity. These attributes brought
      myriad speculations about the nature of Venus, its climate, and the possibility
      of life existing there in some form. Mars also harbored interest as a place where
      life had or might still exist. Seasonal changes on Mars were interpreted as due
      to the possible spread and retreat of ice caps and lichen-like vegetation. A core
      element of this belief rested with the climatology of these two planets, as
      observed by astronomers, but these ideas were significantly altered, if not
      dashed during the space age. Missions to Venus and Mars revealed strikingly
      different worlds. The high temperatures and pressures found on Venus supported a
      "runaway greenhouse theory," and Mars harbored an apparently lifeless landscape
      similar to the surface of the Moon. While hopes for Venus as an abode of life
      ended, the search for evidence of past life on Mars, possibly microbial, remains
      a central theme in space exploration. This survey explores the evolution of
      thinking about the climates of Venus and Mars as life-support systems, in
      comparison to Earth. 

PMID- 25371104
TI  - Survival of the fittest: overcoming oxidative stress at the extremes of Acid,
      heat and metal.
AB  - The habitat of metal respiring acidothermophilic lithoautotrophs is perhaps the
      most oxidizing environment yet identified. Geothermal heat, sulfuric acid and
      transition metals contribute both individually and synergistically under aerobic
      conditions to create this niche. Sulfuric acid and metals originating from
      sulfidic ores catalyze oxidative reactions attacking microbial cell surfaces
      including lipids, proteins and glycosyl groups. Sulfuric acid also promotes
      hydrocarbon dehydration contributing to the formation of black "burnt" carbon.
      Oxidative reactions leading to abstraction of electrons is further impacted by
      heat through an increase in the proportion of reactant molecules with sufficient
      energy to react. Collectively these factors and particularly those related to
      metals must be overcome by thermoacidophilic lithoautotrophs in order for them to
      survive and proliferate. The necessary mechanisms to achieve this goal are
      largely unknown however mechanistics insights have been gained through genomic
      studies. This review focuses on the specific role of metals in this extreme
      environment with an emphasis on resistance mechanisms in Archaea. 

PMID- 25371107
TI  - Effect of the blockade of the IL-23-Th17-IL-17A pathway on streptozotocin-induced
      diabetic retinopathy in rats.
AB  - PURPOSE: T helper 17 (Th17) cells are believed to play a critical role in the
      chronic inflammatory and immune response in streptozotocin (STZ)-induced
      retinopathy. The purpose of our study was to investigate the effect of the IL-23
      Th17-IL-17A pathway via the blood-retinal barrier on STZ-induced diabetic
      retinopathy in rats. METHODS: The ratio of IL-17A(+)CD4(+) T cells in peripheral
      blood mononuclear cells of STZ-treated and wild-type rats was determined using
      flow cytometry. The IL-17A mRNA levels in the retinas were measured using real
      time PCR. The protein expression of IL-17A in the peripheral blood and retinas
      was measured using an ELISA kit. The retinal structure in the wild-type and STZ
      treated rats was examined using hematoxylin and eosin (H&E) staining.
      Additionally, the permeability of the blood-retinal barrier was quantified using
      the Evans blue technique. RESULTS: The ratio of IL-17A(+)CD4(+) T cells in
      peripheral blood mononuclear cells was markedly increased in rats treated with
      STZ compared to the wild-type group. IL-17A protein levels in the peripheral
      blood and retinas were also significantly elevated in STZ-treated rats. However,
      when the anti-IL 23Rp19 antibody was injected into the vitreous cavity in the
      eyes of STZ-treated rats for a period of one week, retinal pigment epithelium
      cells became markedly tighter, and micrangium and endothelial cells were
      significantly reduced. The expression of IL-17A mRNA and protein in the retina
      also decreased significantly compared with the placebo-treated group.
      CONCLUSIONS: This study provided further insight into the function of the IL-23
      Th17-IL-17A pathway in STZ-induced diabetic retinopathy in rats. Local injection
      of the anti-IL-23Rp19 antibody may improve the structure of the blood-retinal
      barrier, thus offering the potential for treatment using intravitreal anti-IL
      23Rp19 antibodies.

PMID- 25371109
TI  - HIV, Chlamydia, Gonorrhea, and Primary and Secondary Syphilis among American
      Indians and Alaska Natives Within Indian Health Service Areas in the United
      States, 2007-2010.
AB  - National rates from human immunodeficiency virus (HIV) and sexually transmitted
      disease (STD) surveillance may not effectively convey the impact of HIV and STDs
      on American Indian/Alaska Native (AI/AN) communities. Instead, we compared
      average annual diagnosis rates per 100,000 population of HIV, chlamydia (CT),
      gonorrhea (GC), and primary and secondary (P&S) syphilis, from 2007 to 2010,
      among AI/AN aged >= 13 years residing in 625 counties in the 12 Indian Health
      Service Areas, all AI/AN, and all races/ethnicities to address this gap. AI/AN
      comprised persons reported as AI/AN only, with or without Hispanic ethnicity. Out
      of 12 IHS Areas, 10 had higher case rates for CT, 3 for GC, and 4 for P&S
      syphilis compared to rates for all races/ethnicities. Eight Areas had higher HIV
      diagnosis rates than for all AI/AN, but HIV rates for all IHS Areas were lower
      than national rates for all races/ethnicities. Two IHS Areas ranking highest in
      rates of CT and GC and four Areas with highest P&S syphilis also had high HIV
      rates. STD and HIV rates among AI/AN were greater in certain IHS Areas than
      expected from observing national rates for AI/AN. Integrated surveillance of
      overlapping trends in STDs and HIV may be useful in guiding prevention efforts
      for AI/AN populations.

PMID- 25371108
TI  - Comparison of costs and discharge outcomes for patients hospitalized for ischemic
      or hemorrhagic stroke with or without atrial fibrillation in the United States.
AB  - This retrospective analysis investigated the impact of baseline clinical
      characteristics, including atrial fibrillation (AF), on hospital discharge status
      (to home or continuing care), mortality, length of hospital stay, and treatment
      costs in patients hospitalized for stroke. The analysis included adult patients
      hospitalized with a primary diagnosis of ischemic or hemorrhagic stroke between
      January 2006 and June 2011 from the premier alliance database, a large nationally
      representative database of inpatient health records. Patients included in the
      analysis were categorized as with or without AF, based on the presence or absence
      of a secondary listed diagnosis of AF. Irrespective of stroke type (ischemic or
      hemorrhagic), AF was associated with an increased risk of mortality during the
      index hospitalization event, as well as a higher probability of discharge to a
      continuing care facility, longer duration of stay, and higher treatment costs. In
      patients hospitalized for a stroke event, AF appears to be an independent risk
      factor of in-hospital mortality, discharge to continuing care, length of hospital
      stay, and increased treatment costs. 

PMID- 25371110
TI  - Friends with benefits: dating practices of rural high school and college
      students.
AB  - A specific type of casual relationship known as "Friends with Benefits" (FWB) is
      becoming increasingly popular among youth. However, current research has often
      examined the dating practices of urban college students, resulting in a limited
      understanding of rural youth. Potential risk factors associated with FWB include
      increased sexual risk behavior. The current study examined FWB among rural high
      school and college students (N = 100). No differences emerged in the rates of FWB
      between high school and college youth or males and females. College students and
      those participating in FWB reported more sexual risk behavior than high school
      students and those never engaging in FWB. Results suggest that FWB relationships
      are common among high school students and rural youth.

PMID- 25371111
TI  - Impact of multiple transarterial chemoembolization treatments on hepatocellular
      carcinoma for patients awaiting liver transplantation.
AB  - Transarterial chemoembolization (TACE) is a common treatment for patients with
      hepatocellular carcinoma (HCC) who are awaiting liver transplantation (LT). The
      aim of this study was to assess the impact of multiple TACE treatments on tumor
      necrosis, tumor recurrence, and survival in these patients. A retrospective
      analysis was performed for 104 consecutive patients undergoing LT for HCC from
      January 2002 to December 2009 who were treated with TACE before LT. The number of
      TACE treatments was not associated with tumor necrosis in the explant. After a
      median follow-up of 69 months (range = 0-123 months), 14 of the 104 patients
      (13%) developed recurrent HCC after LT. Recurrence had a significant relationship
      with a short interval between the diagnosis of HCC and LT (<=6 months) in
      univariate and multivariate analyses [P = 0.029, odds ratio (OR) = 19.2].
      Patients subjected to a single TACE treatment were more likely to experience
      recurrence, although this finding was not confirmed in the multivariate analysis.
      No significant relationship was observed between tumor necrosis in the explant
      and recurrence. The mean overall survival was 102.8 months (95% confidence
      interval = 94.9-110.8 months) with 1-, 3-, and 5-year survival rates of 91%, 89%,
      and 84% respectively. In the univariate survival analysis, the presence of
      ascites before TACE, a waiting time <= 9 months, and tumor characteristics at the
      pathological examination were statistically associated with shorter survival. In
      the multivariate analysis, only vascular invasion (P < 0.001, OR = 7.99) remained
      independently associated with shorter survival. The number of TACE treatments was
      not associated with survival. In conclusion, multiple TACE treatments were not
      associated with a higher risk of recurrence or shorter survival. Continued use of
      TACE should be considered as indicated if the patient and lesions are suitable
      for retreatment. A shorter waiting time before LT is related to an increased risk
      of recurrence and decreased survival after LT for HCC. These data could reflect
      the presence of more aggressive tumor biology and may be useful for guiding organ
      allocation policy to consider a minimum observation period before LT for regions
      with shorter wait times.

PMID- 25371112
TI  - Structure and dynamics of DRD4 bound to an agonist and an antagonist using in
      silico approaches.
AB  - Human dopamine receptor D4 (DRD4), a member of G-protein coupled receptor (GPCR)
      family, plays a central role in cell signaling and trafficking. Dysfunctional
      activity of DRD4 can lead to several psychiatric conditions and, therefore,
      represents target for many neurological disorders. However, lack of atomic
      structure impairs our understanding of the mechanism regulating its activity.
      Here, we report the modeled structure of DRD4 alone and in complex with dopamine
      and spiperone, its natural agonist and antagonist, respectively. To assess the
      conformational dynamics induced upon ligand binding, all-atom explicit solvent
      molecular dynamics simulations in membrane environment were performed.
      Comprehensive analyses of simulations reveal that agonist binding triggers a
      series of conformational changes in the transmembrane region, including
      rearrangement of residues, characteristic of transmission and tyrosine toggle
      molecular switches. Further, the trajectories indicate that a loop region in the
      intracellular region--ICL3, is significantly dynamic in nature, mainly due to the
      side-chain movements of conserved proline residues involved in SH3 binding
      domains. Interestingly, in dopamine-bound receptor simulation, ICL3 represents an
      open conformation ideal for G protein binding. The structural and dynamical
      information presented here suggest a mode of activation of DRD4, upon ligand
      binding. Our study will help in further understanding of receptor activation, as
      acquiring structural information is crucial for the design of highly selective
      DRD4 ligands.

PMID- 25371113
TI  - Cotton cytochrome P450 CYP82D regulates systemic cell death by modulating the
      octadecanoid pathway.
AB  - Plant oxylipins are derived from unsaturated fatty acids and play roles in plant
      growth and development as well as defence. Although recent studies have revealed
      that fatty acid metabolism is involved in systemic acquired resistance, the
      precise function of oxylipins in plant defence remains unknown. Here we report a
      cotton P450 gene SILENCE-INDUCED STEM NECROSIS (SSN), RNAi suppression of which
      causes a lesion mimic phenotype. SSN is also involved in jasmonate metabolism and
      the response to wounding. Fatty acid and oxylipin metabolite analysis showed that
      SSN overexpression causes hyperaccumulation of hydroxide and ketodiene fatty
      acids and reduced levels of 18:2 fatty acids, whereas silencing causes an
      imbalance in LOX (lipoxygenase) expression and excessive hydroperoxide fatty acid
      accumulation. We also show that an unknown oxylipin-derived factor is a putative
      mobile signal required for systemic cell death and hypothesize that SSN acts as a
      valve to regulate HR on pathogen infection. 

PMID- 25371114
TI  - Optimising parallel R correlation matrix calculations on gene expression data
      using MapReduce.
AB  - BACKGROUND: High-throughput molecular profiling data has been used to improve
      clinical decision making by stratifying subjects based on their molecular
      profiles. Unsupervised clustering algorithms can be used for stratification
      purposes. However, the current speed of the clustering algorithms cannot meet the
      requirement of large-scale molecular data due to poor performance of the
      correlation matrix calculation. With high-throughput sequencing technologies
      promising to produce even larger datasets per subject, we expect the performance
      of the state-of-the-art statistical algorithms to be further impacted unless
      efforts towards optimisation are carried out. MapReduce is a widely used high
      performance parallel framework that can solve the problem. RESULTS: In this
      paper, we evaluate the current parallel modes for correlation calculation methods
      and introduce an efficient data distribution and parallel calculation algorithm
      based on MapReduce to optimise the correlation calculation. We studied the
      performance of our algorithm using two gene expression benchmarks. In the micro
      benchmark, our implementation using MapReduce, based on the R package RHIPE,
      demonstrates a 3.26-5.83 fold increase compared to the default Snowfall and 1.56
      1.64 fold increase compared to the basic RHIPE in the Euclidean, Pearson and
      Spearman correlations. Though vanilla R and the optimised Snowfall outperforms
      our optimised RHIPE in the micro-benchmark, they do not scale well with the macro
      benchmark. In the macro-benchmark the optimised RHIPE performs 2.03-16.56 times
      faster than vanilla R. Benefiting from the 3.30-5.13 times faster data
      preparation, the optimised RHIPE performs 1.22-1.71 times faster than the
      optimised Snowfall. Both the optimised RHIPE and the optimised Snowfall
      successfully performs the Kendall correlation with TCGA dataset within 7 hours.
      Both of them conduct more than 30 times faster than the estimated vanilla R.
      CONCLUSIONS: The performance evaluation found that the new MapReduce algorithm
      and its implementation in RHIPE outperforms vanilla R and the conventional
      parallel algorithms implemented in R Snowfall. We propose that MapReduce
      framework holds great promise for large molecular data analysis, in particular
      for high-dimensional genomic data such as that demonstrated in the performance
      evaluation described in this paper. We aim to use this new algorithm as a basis
      for optimising high-throughput molecular data correlation calculation for Big
      Data.

PMID- 25371115
TI  - Scoring System to Predict Pancreatic Fistula After Pancreaticoduodenectomy: A UK
      Multicenter Study.
AB  - OBJECTIVE: To validate a preoperative predictive score of postoperative
      pancreatic fistula (POPF). Other risk factors for POPF were sought in an attempt
      to improve the score. BACKGROUND: POPF is the major contributor to morbidity
      after pancreaticoduodenectomy (PD). A preoperative score [using body mass index
      (BMI) and pancreatic duct width] to predict POPF was tested upon a multicenter
      patient cohort to assess its performance. METHODS: Patients undergoing PD at 8 UK
      centers were identified. The association between the score and other pre-, intra
      , and postoperative variables with POPF was assessed. RESULTS: A total of 630
      patients underwent PD with 141 occurrences of POPF (22.4%). BMI, perirenal fat
      thickness, pancreatic duct width on computed tomography and at operation,
      bilirubin, pancreatojejunostomy technique, underlying pathology, T stage, N
      stage, R status, and gland firmness were all significantly associated with POPF.
      The score predicted POPF (P < 0.001) with a higher predictive score associated
      with increasing severity of POPF (P < 0.001). Stepwise multivariate analysis of
      pre-, intra-, and postoperative variables demonstrated that only the score was
      consistently associated with POPF. A table correlating the risk score to actual
      risk of POPF was created. CONCLUSIONS: The predictive score performed well and
      could not be improved. This provides opportunities for individualizing patient
      consent and selection, and treatment and research applications.

PMID- 25371116
TI  - Is It Time to Change Practice of Routine Colonoscopy After Acute Diverticulitis?

PMID- 25371117
TI  - Considerations in the Early Termination of Clinical Trials in Surgery.

PMID- 25371119
TI  - Use of Mesh During Ventral Hernia Repair in Clean-contaminated and Contaminated
      Cases: Outcomes of 33,832 Cases.

PMID- 25371118
TI  - Temporal Patterns of Circulating Inflammation Biomarker Networks Differentiate
      Susceptibility to Nosocomial Infection Following Blunt Trauma in Humans.
AB  - BACKGROUND: Severe traumatic injury can lead to immune dysfunction that renders
      trauma patients susceptible to nosocomial infections (NI) and prolonged intensive
      care unit (ICU) stays. We hypothesized that early circulating biomarker patterns
      following trauma would correlate with sustained immune dysregulation associated
      with NI and remote organ failure. METHODS: In a cohort of 472 blunt trauma
      survivors studied over an 8-year period, 127 patients (27%) were diagnosed with
      NI versus 345 trauma patients without NI. To perform a pairwise, case-control
      study with 1:1 matching, 44 of the NI patients were compared with 44 no-NI trauma
      patients selected by matching patient demographics and injury characteristics.
      Plasma obtained upon admission and over time were assayed for 26 inflammatory
      mediators and analyzed for the presence of dynamic networks. RESULTS: Significant
      differences in ICU length of stay (LOS), hospital LOS, and days on mechanical
      ventilation were observed in the NI patients versus no-NI patients. Although NI
      was not detected until day 7, multiple mediators were significantly elevated
      within the first 24 hours in patients who developed NI. Circulating inflammation
      biomarkers exhibited 4 distinct dynamic patterns, of which 2 clearly distinguish
      patients destined to develop NI from those who did not. Mediator network
      connectivity analysis revealed a higher, coordinated degree of activation of both
      innate and lymphoid pathways in the NI patients over the initial 24 hours.
      CONCLUSIONS: These studies implicate unique dynamic immune responses, reflected
      in circulating biomarkers that differentiate patients prone to persistent
      critical illness and infections following injury, independent of mechanism of
      injury, injury severity, age, or sex.

PMID- 25371120
TI  - Effect of Simvastatin on Physiological and Biological Outcomes in Patients
      Undergoing Esophagectomy.

PMID- 25371121
TI  - Prospective Analysis of 8589 Patients With Colonic Cancer: Can We Conclude That
      Anastomotic Leak Is a Prognostic Factor?

PMID- 25371122
TI  - Extended Venous Thromboembolism Prophylaxis After Colorectal Cancer Resection: A
      UK Perspective.

PMID- 25371123
TI  - Robot-assisted Minimally Invasive Distal Pancreatectomy Is Superior to the
      Laparoscopic Technique.

PMID- 25371124
TI  - Reply to "Letter to Editor Concerning the Article-Effect of the World Health
      Organization Checklist on Patient Outcomes: A Stepped Wedge Cluster Randomized
      Controlled Trial".

PMID- 25371125
TI  - Reply to Letter: "Extended Venous Thromboembolism Prophylaxis After Colorectal
      Cancer Resection: A UK Perspective".

PMID- 25371126
TI  - Effect of the World Health Organization Checklist on Patient Outcomes: A Stepped
      Wedge Cluster Randomized Controlled Trial.

PMID- 25371127
TI  - Re: Does Surgical Ward Round Quality Really Impact on Patient Outcomes?

PMID- 25371128
TI  - Reply to letter: "Updated recommendations for control of surgical site
      infections".

PMID- 25371129
TI  - Protein expression profiling predicts graft performance in clinical ex vivo lung
      perfusion.
AB  - OBJECTIVES: To study the impact of ex vivo lung perfusion (EVLP) on cytokines,
      chemokines, and growth factors and their correlation with graft performance
      either during perfusion or after transplantation. BACKGROUND: EVLP is a modern
      technique that preserves lungs on normothermia in a metabolically active state.
      The identification of biomarkers during clinical EVLP can contribute to the safe
      expansion of the donor pool. METHODS: High-risk brain death donors and donors
      after cardiac death underwent 4 to 6 hours EVLP. Using a multiplex magnetic bead
      array assay, we evaluated analytes in perfusate samples collected at 1 hour and 4
      hours of EVLP. Donor lungs were divided into 3 groups: (I) Control: bilateral
      transplantation with good early outcome [absence of primary graft dysfunction-
      (PGD) grade 3]; (II) PGD3: bilateral transplantation with PGD grade 3 anytime
      within 72 hours; (III) Declined: lungs unsuitable for transplantation after EVLP.
      RESULTS: Of 50 cases included in this study, 27 were in Control group, 7 in PGD3,
      and 16 in Declined. From a total of 51 analytes, 34 were measurable in
      perfusates. The best marker to differentiate declined lungs from control lungs
      was stem cell growth factor -beta [P < 0.001, AUC (area under the curve) = 0.86]
      at 1 hour. The best markers to differentiate PGD3 cases from controls were
      interleukin-8 (P < 0.001, AUC = 0.93) and growth-regulated oncogene-alpha (P =
      0.001, AUC = 0.89) at 4 hours of EVLP. CONCLUSIONS: Perfusate protein expression
      during EVLP can differentiate lungs with good outcome from lungs PGD3 after
      transplantation. These perfusate biomarkers can be potentially used for more
      precise donor lung selection improving the outcomes of transplantation.

PMID- 25371130
TI  - Cost-effectiveness of Enhanced Recovery Versus Conventional Perioperative
      Management for Colorectal Surgery.
AB  - OBJECTIVE: To determine the cost-effectiveness of enhanced recovery pathways
      (ERPs) versus conventional care for patients undergoing elective colorectal
      surgery. BACKGROUND: ERPs for colorectal surgery are clinically effective, but
      their cost-effectiveness is unknown. METHODS: A multi-institutional prospective
      cohort cost-effectiveness analysis was performed. Adult patients undergoing
      elective colorectal resection at 2 university-affiliated institutions from
      October 2012 to October 2013 were enrolled. One center used an ERP, whereas the
      other did not. Postoperative outcomes were recorded up to 60 days. Total costs
      were reported in 2013 Canadian dollars. Effectiveness was measured using the SF
      6D, a health utility measure validated for postoperative recovery. Uncertainty
      was expressed using bootstrapped estimates (10,000 repetitions). RESULTS: A total
      of 180 patients were included (conventional care: n = 95; ERP: n = 95). There
      were no differences in patient characteristics except for a higher proportion of
      laparoscopy in the ERP group. Mean length of stay was shorter in the ERP group
      (6.5 vs 9.8 days; P = 0.017), but there were no differences in complications or
      readmissions. Patients in the ERP group returned to work quicker and had less
      caregiver burden. There was no difference in quality of life between the 2
      groups. The cost of the ERP program was $153 per patient. Overall societal costs
      were lower in the ERP group (mean difference = -2985; 95% confidence interval, 
      5753 to -373). The ERP had a greater than 99% probability of cost-effectiveness.
      The results were insensitive to a range of assumptions and subgroups.
      CONCLUSIONS: Enhanced recovery is cost-effective compared with conventional
      perioperative management for elective colorectal resection.

PMID- 25371131
TI  - Performing the ALPPS Procedure by Anterior Approach and Liver Hanging Maneuver.

PMID- 25371132
TI  - "Clinical outcome after radical excision of moderate-severe endometriosis with or
      without bowel resection and reanastomosis: a prospective cohort study" by
      Meuleman et al. Ann Surg. 2013; April 10-the gold rush: are we there yet?

PMID- 25371133
TI  - The Challenge of Clinical Diagnosis of Appendicitis and Nonoperative Management
      of Patients With Right Lower Abdominal Pain.

PMID- 25371134
TI  - Electrochemical impedance spectroscopy in understanding the influence of
      ultrasonic dental scaling on the dental structure-dental filling interface.
AB  - The purpose of this study was to investigate the effect of ultrasonic scaling on
      teeth restored with a light-cured resin. Ultrasonic scaling is a very popular
      periodontal therapy among dentists, and used for the removal of dental plaque and
      calculus in order to reduce and eliminate inflammation. Given the fact that most
      ultrasonic devices are used at high frequencies to perform scaling, undesirable
      consequences, such as loss of adhesion and increase in surface roughness, may
      occur in teeth that have been restored with light-cured resins. Electrochemical
      impedance spectroscopy (EIS) and scanning electron microscopy were used to
      investigate the effects of ultrasonic treatments at the dental material-hard
      dental tissue interface. After ultrasonic scaling, EIS measurements were
      performed on a human tooth that had been restored with a light-cured resin
      filling. The data were analyzed and the influence of ultrasound was shown after
      visualization of the hard dental tissues and the dental material as equivalent
      electrical circuits. The study revealed, through EIS measurements, that
      ultrasonic scaling affected the resistance of the light-cured resin filling and
      dentin, whereas the enamel was affected only slightly. Scanning electron
      microscopy revealed an increase in roughness of the dental material. 

PMID- 25371135
TI  - Successful omalizumab treatment in chronic spontaneous urticaria is associated
      with lowering of serum IL-31 levels.

PMID- 25371136
TI  - Modeling nonequilibrium adsorption of MIB and sulfamethoxazole by powdered
      activated carbon and the role of dissolved organic matter competition.
AB  - This study demonstrates that the ideal adsorbed solution theory-equivalent
      background compound (IAST-EBC) as a stand-alone model can simulate and predict
      the powdered activated carbon (PAC) adsorption of organic micropollutants found
      in drinking water sources in the presence of background dissolved organic matter
      (DOM) under nonequilibrium conditions. The IAST-EBC represents the DOM
      competitive effect as an equivalent background compound (EBC). When adsorbing 2
      methylisoborneol (MIB) with PAC, the EBC initial concentration was a similar
      percentage, on average 0.51%, of the dissolved organic carbon in eight
      nonwastewater impacted surface waters. Using this average percentage in the IAST
      EBC model yielded good predictions for MIB removal in two nonwastewater impacted
      waters. The percentage of competitive DOM was significantly greater in wastewater
      impacted surface waters, and varied markedly in DOM size fractions. Fluorescence
      parameters exhibited a strong correlation with the percentage of competitive DOM
      in these waters. Utilizing such correlations in the IAST-EBC successfully modeled
      MIB and sulfamethoxazole adsorption by three different PACs in the presence of
      DOM that varied in competitive effect. The influence of simultaneous coagulant
      addition on PAC adsorption of micropollutants was also investigated. Coagulation
      caused the DOM competitive effect to increase and decrease with MIB and
      sulfamethoxazole, respectively. 

PMID- 25371137
TI  - Carbon nanotube-bilirubin oxidase bioconjugate as a new biofuel cell label for
      self-powered immunosensor.
AB  - We demonstrated a biofuel cells (BFCs)-based self-powered sensing system for the
      detection of Nepsilon-(carboxymethyl)lysine (CML), in which the bilirubin oxidase
      (BOD)-carbon nanotube (CNT) bioconjugate modified with antibody acted as a
      biocatalyst for enhancing O2 reduction in the biocathode, as well as the
      transducing enzyme for signaling magnification. With an increase in the
      concentration of CML, the amount of BOD labels on biocathode surface increases,
      thus leading to the higher output of the as-prepared BFCs. This novel BFCs-based
      self-powered sensor showed a wide linear range for analyzing CML from 1 nM to 100
      MUM with a detection limit of 0.2 nM, which was 50 times more sensitive than that
      determined from the conventional ELISA. Most importantly, our new self-powered
      sensing platform can determine the level of CML in serum samples from multiple
      healthy donors and multiple sclerosis patients, being well in accordance with
      that from the commercial ELISA analysis. 

PMID- 25371138
TI  - Automobile driving in older adults: factors affecting driving restriction in men
      and women.
AB  - OBJECTIVES: To identify factors associated with driving restriction in elderly
      men and women. DESIGN: Prospective cohort study of French drivers from 2003 to
      2009. SETTING: The Three-City Cohort of Bordeaux, a prospective study of 2,104
      people aged 65 and older. PARTICIPANTS: Five hundred twenty-three drivers with a
      mean age of 76 (273 male, 250 female). MEASUREMENTS: Sociodemographic
      characteristics, driving habits, health variables, cognitive evaluation and
      dementia diagnosis. Predementia was defined as no dementia at one follow-up and
      dementia at the next follow-up. RESULTS: Over the 6-year period, 54% of men and
      63% of women stopped driving or reduced the distance they drove. Predementia,
      Parkinson's disease, older age, and a high number of kilometers previously driven
      were common restriction factors in both sexes. Prevalent dementia, depressive
      symptomatology, a decline in one or more instrumental activities of daily living,
      and poor visual working memory were specific factors in men. In women, low
      income, fear of falling, slow processing speed, and severe decline in global
      cognitive performance all affected driving restriction. CONCLUSION: Older women
      restricted their driving activity more than older men, regardless of the number
      of kilometers previously driven, physical health, and cognitive status. Factors
      affecting driving restriction differed according to sex, and women were more
      likely to stop driving than men in the period preceding a dementia diagnosis.

PMID- 25371139
TI  - Primary amino acid catalyzed asymmetric intramolecular Mannich reaction for the
      synthesis of 2-aryl-2,3-dihydro-4-quinolones.
AB  - Primary amino acids are found to be good enantioselective catalysts for the
      direct asymmetric Mannich reaction between 2-amino acetophenone and aldehydes.
      The 2-aryl-2,3-dihydro-4-quinoline products are obtained in moderate to good
      yields and good to high enantioselectivities with 10 mol% of the primary amino
      acid catalyst under mild reaction conditions. 

PMID- 25371140
TI  - Bioinformatic analysis of microRNA expression in Parkinson's disease.
AB  - Parkinson's disease (PD) is a type of movement disorder caused by loss of
      dopamine-producing neurons in the midbrain. In order to identify the synergistic
      microRNA (miRNA) pattern in PD, miRNA and mRNA double expression profiles of PD
      were downloaded. Differentially expressed miRNA and mRNA were identified [P<0.01,
      following false discovery rate (FDR) correction]. A cumulative hypergeometric
      distribution test was then performed to identify synergistic miRNAs (P<0.01,
      following FDR correction). Gene ontology (GO) function and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) pathway annotations were performed to analyze the miRNA
      regulatory target genes. Subsequently, a synergistic miRNA network was
      constructed and miRNAs exhibiting a high degree were identified. In total, 200
      differentially expressed miRNA and 2,966 differentially expressed mRNA were
      identified. In addition, 1,502 synergistic miRNA interactions were identified,
      and miRNAs regulated 304 target genes in total. The GO and KEGG analysis
      demonstrated that these target genes were enriched in biosynthetic and cellular
      biosynthetic processes, the assembly of cellular components in morphogenesis,
      mitogen-activated protein kinase signaling, myometrial relaxation and contraction
      pathways as well as calcium regulation. The miRNA network demonstrated that miR
      627, miR-634, miR-514, miR-563 and miR-613 had a high degree. miRNA with a high
      degree may be associated with the pathogenesis of PD and, therefore, may assist
      in the diagnosis and therapy of PD.

PMID- 25371141
TI  - Antimicrobial peptides: therapeutic potentials.
AB  - The increasing appearance of multidrug-resistant pathogens has created an urgent
      need for suitable alternatives to current antibiotics. Antimicrobial peptides
      (AMPs), which act as defensive weapons against microbes, have received great
      attention because of broad-spectrum activities, unique action mechanisms and rare
      antibiotic-resistant variants. Despite desirable characteristics, they have shown
      limitations in pharmaceutical development due to toxicity, stability and
      manufacturing costs. Because of these drawbacks, only a few AMPs have been tested
      in Phase III clinical trials and no AMPs have been approved by the US FDA yet.
      However, these obstacles could be overcome by well-known methods such as changing
      physicochemical characteristics and introducing nonnatural amino acids,
      acetylation or amidation, as well as modern techniques like molecular targeted
      AMPs, liposomal formulations and drug delivery systems. Thus, the current
      challenge in this field is to develop therapeutic AMPs at a reasonable cost as
      well as to overcome the limitations. 

PMID- 25371142
TI  - Contemporary techniques for coronary CTO revascularization.

PMID- 25371143
TI  - Isolated severe bilateral bronchomalacia: correspondence.

PMID- 25371144
TI  - Diabetes insipidus in pediatric patients.

PMID- 25371145
TI  - Recurrent meningitis in hyper IgE syndrome.

PMID- 25371146
TI  - Chronic obstructive pulmonary disease case finding by community pharmacists: a
      potential cost-effective public health intervention.
AB  - OBJECTIVES: This study aims to pilot a community pharmacy chronic obstructive
      pulmonary disease (COPD) case finding service in England, estimating costs and
      effects. METHODS: Patients potentially at risk of COPD were screened with
      validated tools. Smoking cessation was offered to all smokers identified as
      potentially having undiagnosed COPD. Cost and effects of the service were
      estimated. KEY FINDINGS: Twenty-one community pharmacies screened 238 patients
      over 9 months. One hundred thirty-five patients were identified with potentially
      undiagnosed COPD; 88 were smokers. Smoking cessation initiation provided a
      project gain of 38.62 life years, 19.92 quality-adjusted life years and a cost
      saving of L392.67 per patient screened. CONCLUSIONS: COPD case finding by
      community pharmacists potentially provides cost-savings and improves quality of
      life.

PMID- 25371147
TI  - Worsening heart failure, a critical event during hospital admission for acute
      heart failure: results from the VERITAS study.
AB  - AIMS: Worsening heart failure (WHF) in the first 7 days after an admission for
      acute HF (AHF) has been proposed as a therapeutic target in several recent AHF
      studies and was a co-primary endpoint of the VERITAS studies. METHODS AND
      RESULTS: Patients were randomized within 24 h of admission for AHF. WHF was
      defined as worsening or persistent signs and symptoms of HF requiring additional
      intravenous or mechanical therapy for HF or death within 7 days of randomization.
      Multivariable models were developed to predict the time to WHF through day 7.
      Unadjusted and multivariable-adjusted associations of WHF with the length of stay
      (LOS) of the index hospitalization, and 30- and 90-day outcomes were estimated.
      WHF occurred by day 7 in 27% of the 1347 patients enrolled. Age, co-morbidities,
      and markers of HF severity were moderately predictive of WHF; the C-index for a
      multivariable model for WHF was 0.66. After multivariable adjustment for baseline
      characteristics, WHF was associated with an increase in LOS of 4.33 days [95%
      confidence interval (CI) 3.54-5.13 days], a hazard ratio (HR) for 30-day HF
      readmission or death of 2.43 (95% CI 1.75-3.40), and a HR for 90-day mortality of
      2.57 (95% CI 1.81-3.65), all with P < 0.0001.The associations of WHF with these
      outcomes remained largely unchanged after adjustment for both baseline
      characteristics and changes in markers of renal and hepatic dysfunction during
      the first day of admission. CONCLUSIONS: In patients admitted for AHF, WHF is a
      significant clinical event that is associated with delays in discharge and higher
      rates for readmission and death.

PMID- 25371148
TI  - General synthesis of trifluoromethyl selenides utilizing selenocyanates and
      fluoroform.
AB  - Trifluoromethylated selenoethers are quite rare despite their potential and the
      interest that they generate. A series of trifluoromethylseleno derivatives,
      either primary and secondary aliphatic or aromatic and heterocyclic, is described
      herein by the reaction of easily prepared organic selenocyanates and CuCF3.
      Another beneficial feature of this reaction is the use of fluoroform as a source
      for the CF3 group, a compound whose chemistry is currently being intensively
      researched because it is a potent greenhouse gas that should not be released into
      the atmosphere. 

PMID- 25371149
TI  - Persistence of DNMT3A mutations at long-term remission in adult patients with
      AML.
AB  - Mutations in DNMT3A, the gene encoding DNA methyltransferase 3 alpha, have been
      identified as molecular drivers in acute myeloid leukaemia (AML) with possible
      implications for minimal residual disease monitoring and prognosis. To further
      explore the utility of DNMT3A mutations as biomarkers for AML, we developed
      assays for sensitive detection of recurrent mutations affecting residue R882.
      Analysis of DNA from 298 diagnostic AML samples revealed DNMT3A mutations in 45
      cases (15%), which coincided with mutations in NPM1, FLT3 and IDH1. DNMT3A
      mutations were stable in 12 of 13 patients presenting with relapse or secondary
      myelodysplastic syndrome, but were also present in remission samples from 14
      patients (at allele frequencies of <1-50%) up to 8 years after initial AML
      diagnosis, despite the loss of all other molecular AML markers. The mutant DNMT3A
      allele burden was not related to the clinical course of disease. Cell sorting
      demonstrated the presence of DNMT3A mutations in leukaemic blasts, but also at
      lower allele frequencies in T and B-cells from the same patients. Our data are
      consistent with the recent finding of preleukaemic stem cells in AML, which are
      resistant to chemotherapy. The persistence of DNMT3A mutations during remission
      may have important implications for the management of AML.

PMID- 25371150
TI  - The hepatic transcriptome of young suckling and aging intrauterine growth
      restricted male rats.
AB  - Intrauterine growth restriction leads to the development of adult onset
      obesity/metabolic syndrome, diabetes mellitus, cardiovascular disease,
      hypertension, stroke, dyslipidemia, and non-alcoholic fatty liver
      disease/steatohepatitis. Continued postnatal growth restriction has been shown to
      ameliorate many of these sequelae. To further our understanding of the mechanism
      of how intrauterine and early postnatal growth affects adult health we have
      employed Affymetrix microarray-based expression profiling to characterize hepatic
      gene expression of male offspring in a rat model of maternal nutrient restriction
      in early and late life. At day 21 of life (p21) combined intrauterine and
      postnatal calorie restriction treatment led to expression changes in circadian,
      metabolic, and insulin-like growth factor genes as part of a larger
      transcriptional response that encompasses 144 genes. Independent and controlled
      experiments at p21 confirm the early life circadian, metabolic, and growth factor
      perturbations. In contrast to the p21 transcriptional response, at day 450 of
      life (d450) only seven genes, largely uncharacterized, were differentially
      expressed. This lack of a transcriptional response identifies non-transcriptional
      mechanisms mediating the adult sequelae of intrauterine growth restriction.
      Independent experiments at d450 identify a circadian defect as well as validate
      expression changes to four of the genes identified by the microarray screen which
      have a novel association with growth restriction. Emerging from this rich dataset
      is a portrait of how the liver responds to growth restriction through circadian
      dysregulation, energy/substrate management, and growth factor modulation.

PMID- 25371151
TI  - Reply "Endoscopic therapy with 2-octyl-cyanoacrylate for the treatment of gastric
      varices": optimizing the cyanoacrylate injection in the treatment of gastric
      varices.

PMID- 25371152
TI  - Persisting early hypotension: is this why necrosis gets infected in acute
      pancreatitis?

PMID- 25371153
TI  - Utility of evaluating HCV in an uninsured population.
AB  - OBJECTIVES: Although effective HCV treatment is available, it can be difficult to
      access for uninsured, urban patients. Our aim was to assess the utility of
      evaluation and outcomes in the uninsured with HCV when access to health care and
      treatment with triple therapy is provided. METHODS: We performed a retrospective
      review of consecutive patients referred for HCV from 2011 to June 2013 to an
      indigent HCV clinic. The primary outcomes were assessment of disease severity by
      noninvasive means and initiation of therapy. RESULTS: We identified 350 patients:
      mean age 50.6, 84 % with no insurance, 62 % men, 58 % black, 91 % HCV treatment
      naive. Of these, 148 underwent liver biopsy and 68 % had F0-F1 and 10 % had F3-F4
      fibrosis. FIB-4 and APRI were highly correlated (r = 0.9; p < .0001) and
      correctly classified patients by fibrosis strata (F0-F1, F2, and F3-F4; p =
      .0004). When combined, a FIB-4 <=1.5 and APRI <=0.5 correctly classified the
      absence of advanced disease in 97 % (p < .0001). Of those evaluated, 39 (11 %)
      went on to HCV treatment. Of those not in a clinical trial, 51 % completed
      treatment with SVR in 61 % with genotype 1 and 75 % in genotypenon-1. Of those
      not treated (n = 309), the most common reasons were mild disease (16 %), lost to
      follow-up (23 %), ongoing alcohol or substance abuse (24 %), and uncontrolled
      depression (10 %). CONCLUSION: Noninvasive assessment can accurately exclude
      advanced fibrosis. Despite access to care, the utility of evaluating to initiate
      HCV treatment is low suggesting that eliminating the barrier to health care may
      not increase HCV treatment.

PMID- 25371154
TI  - Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes
      of Patients with Hepatocellular Carcinoma.
AB  - BACKGROUND: Aberrant signaling mediated by the mammalian target of rapamycin
      (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating
      that mTOR is a candidate for targeted therapy. mTOR forms two complexes called
      mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor).
      There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC.
      METHODS: We studied 62 patients with HCC who underwent curative resection. We
      used univariate and multivariate analyses to identify factors that potentially
      influence disease and overall survival after hepatectomy. The mRNA and protein
      levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed
      using quantitative RT-PCR, immunohistochemistry and Western blotting.
      RESULTS/CONCLUSION: High ratio of the levels of rictor and raptor mRNAs in tumors
      was identified as independent prognostic indicators for disease-free survival.
      Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor,
      respectively, were identified as independent indicators of overall survival. HCC
      is likely to recur early after hepatic resection in patients with high levels of
      mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We
      conclude that analysis of mTOR expression in cancer tissues represents an
      essential strategy to predict HCC recurrence after curative treatment.

PMID- 25371156
TI  - An association between migraines and heart anomalies-true or false? A heart
      ultrasound study using cTTE in migraine patients and control participants.
AB  - DESIGN: A migraine is a common neurological disorder that often coexists with
      other illnesses including heart abnormalities, such as patent foramen ovale
      (PFO), atrial septal aneurysm (ASA), and mitral valve prolapse (MVP). OBJECTIVE:
      The aim of our study was to evaluate the occurrence of some heart abnormalities
      in migraine patients by routine and contrast transthoracic echocardiography.
      SUBJECTS AND METHODS: We assessed the occurrence of PFO, ASA, and MVP in 96
      patients with migraine without aura (87 females), in 62 patients with migraine
      with aura (41 females) and in 53 healthy persons (40 females). RESULTS: In
      comparison with our control group, only the prevalence of PFO was statistically
      higher in patients with migraine (P = 0.03) and especially with aura (P = 0.01).
      We did not find any statistically significant differences between the occurrence
      of ASA or MVP in migraine and control groups. CONCLUSION: The results of our
      study raise the question of the heart's role in the mechanism of migraine
      attacks. If the occurrence of migraine with aura had been related to some heart
      abnormalities, the pathophysiology of migraine attacks may have some connection
      to some heart dysfunction. Resolving the association between migraine and
      comorbid cardiac conditions might shed light on the underlying mechanisms of
      migraines and even result in a different treatment strategy. However, we do not
      find any clear connection between PFP, ASA, and MVP, and migraine occurrence.

PMID- 25371157
TI  - Mervyn Susser and community psychiatry.
AB  - Mervyn Susser's contributions to community psychiatry from 1957-1968 comprised a
      creative and significant phase of his career, though less well known than his
      other work. This included work in Salford, a town next to Manchester, where he
      developed a programme to improve community health (including mental health care),
      as well as a programme of research on mental disorders. The publication of his
      book, Community Psychiatry: Epidemiologic and Social Themes (1968) attempted to
      set the stage for the practice of psychiatry in the community and to establish a
      future direction for development of the field.

PMID- 25371155
TI  - Roles of Toll-Like Receptor 4, IkappaB Kinase, and the Proteasome in the
      Intestinal Alterations Caused by Sepsis.
AB  - BACKGROUND: Lipopolysaccharide decreases intestinal contractility and induces the
      production of cytokines, which play an important role in the pathogenesis of
      sepsis. AIM: The objective of the present study was to examine the role of Toll
      like receptor 4, IkappaB kinase, and the proteasome in the intestinal alterations
      induced by lipopolysaccharide. METHODS: Sepsis was induced in rabbits by
      intravenous injection of lipopolysaccharide. Contractility studies of rabbit
      duodenum were performed in an organ bath. Expressions of interleukin-1beta,
      interleukin-6, interleukin-8, interleukin-10, IkappaB kinase-alpha, IkappaB
      kinase-beta, IkappaB kinase-gamma, and the proteasome mRNA were determined by RT
      PCR on rabbit duodenum. RESULTS: Neomycin and polymyxin B (Toll-like receptor 4
      inhibitors), IKK NBD peptide (IkappaB kinase complex inhibitor), and MG-132
      (proteasome inhibitor) blocked partially the effects of lipopolysaccharide on the
      acetylcholine-, prostaglandin E2-, substance P-, and KCl-induced contractions in
      the longitudinal and circular smooth muscle of rabbit duodenum.
      Lipopolysaccharide increased the mRNA expression of interleukin-6 and interleukin
      8 in duodenal tissue, and this effect was partly reversed by neomycin, polymyxin
      B, IKK NBD peptide, and MG-132. IkappaB kinase-alpha, IkappaB kinase-beta,
      IkappaB kinase-gamma, and the proteasome mRNA expressions was not affected by
      lipopolysaccharide treatment. CONCLUSIONS: Toll-like receptor 4, the IkappaB
      kinase complex, and the proteasome could be therapeutic targets in the treatment
      of sepsis symptoms in the intestine.

PMID- 25371158
TI  - A novel human interleukin-24 peptide created by computer-guided design
      contributes to suppression of proliferation in esophageal squamous cell carcinoma
      Eca-109 cells.
AB  - Based on the three-dimensional modeling structure of human interleukin-24 (hIL
      24) and its most likely active position predicted by solvent accessibility and
      apparent electrostatic properties, a novel hIL-24 peptide M1 was created by
      computer-guided molecular design. The cytotoxicity and cell selectivity of M1
      were examined in three human carcinoma cell lines and one normal human embryo
      lung fibroblast cell line (HEL). MTT assay showed that M1 induced growth arrest
      in two IL-20 receptor complex-positive cancer cell lines (the esophageal squamous
      cell carcinoma cell line Eca-109 and the melanoma cell line A375), and antibodies
      against IL-24 or IL-20 receptor complexes significantly neutralized the
      inhibitory activity. Moreover, M1 had almost no cytotoxicity on the lung cancer
      A549 cell line, which lacks a full complement of the IL-20 receptor complexes, or
      on HEL cells that express the IL-20 receptor complexes. These findings
      demonstrate that M1 could act as an excellent candidate for the induction of
      growth arrest on receptor complex-positive cancer cells. In summary, the M1
      peptide may represent a novel anticancer agent for esophageal squamous cell
      carcinoma therapy due to its cancer cell selectivity and its relatively low
      cytotoxicity to normal cells. 

PMID- 25371159
TI  - Ethnic/National origin influence on normal range of motion: comment on the
      article by Assassi et Al.

PMID- 25371160
TI  - Development of poly(aspartic acid-co-malic acid) composites for calcium carbonate
      and sulphate scale inhibition.
AB  - Polyaspartic acid (PSI) is suitable for the inhibition of inorganic scale
      deposition. To enhance its scale inhibition efficiency, PSI was modified by
      reacting aspartic acid with malic acid (MA) using thermal polycondensation
      polymerization. This reaction resulted in poly(aspartic acid-co-malic acid) (PSI
      co-MA) dual polymer. The structural, chemical and thermal properties of the dual
      polymers were analysed by using scanning electron microscopy, Fourier transform
      infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and
      gel permeation chromatography. The effectiveness of six different molar ratios of
      PSI-co-MA dual polymer for calcium carbonate and calcium sulphate scale
      inhibition at laboratory scale batch experiments was evaluated with synthetic
      brine solution at selected doses of polymer at 65-70 degrees C by the static
      scale test method. The performance of PSI-co-MA dual polymer for the inhibition
      of calcium carbonate and calcium sulphate precipitation was compared with that of
      a PSI single polymer. The PSI-co-MA exhibited excellent ability to control
      inorganic minerals, with approximately 85.36% calcium carbonate inhibition and
      100% calcium sulphate inhibition at a level of 10 mg/L PSI-co-MA, respectively.
      Therefore, it may be reasonably concluded that PSI-co-MA is a highly effective
      scale inhibitor for cooling water treatment applications. 

PMID- 25371161
TI  - Prediction of fruit and vegetable intake: The importance of contextualizing
      motivation.
AB  - OBJECTIVES: Motivation is identified as a key antecedent of self-regulated
      behaviour, such as eating fruit and vegetables. However, inaccurate measurement
      of this construct may lead to poor prediction of behaviour and inflate the impact
      of post-motivational factors, such as planning, in models of health behaviour.
      This study explored the properties of a newly identified measure of motivation,
      termed behavioural resolve (Rhodes & Horne, 2013, Psychol. Sport Exerc., 14, 455
      460), in relation to intention, planning, and fruit and vegetable intake (FVI).
      DESIGN: Prospective self-report survey. METHOD: University students living in the
      United Kingdom completed two online surveys. The first assessed demographic and
      predictor variables (intention, behavioural resolve, action planning, and coping
      planning). The second, completed approximately 2 weeks later, measured average
      daily FVI and perceived experience of obstacles to FVI. At Time 1, there were 195
      respondents, with 139 providing follow-up data. RESULTS: All predictor variables
      were significantly correlated with FVI. Two independent multiple hierarchical
      regression analyses revealed that both intention and behavioural resolve were
      significant predictors of FVI, but behavioural resolve explained greater FVI
      variance (40.1%) than intention (36.4%). Furthermore, action planning showed
      incremental predictive utility over intention, but not behavioural resolve, in
      predicting FVI. CONCLUSIONS: The results indicated that motivation is an
      important determinant of FVI for students, with behavioural resolve demonstrating
      advantages over intention as a measure of this domain and a predictor of FVI
      behaviour.

PMID- 25371162
TI  - Diblock copolymers of polyethylene glycol and a polymethacrylamide with side
      chains containing twin ortho ester rings: synthesis, characterization, and
      evaluation as potential pH-responsive micelles.
AB  - The diblock copolymer, PEG-b-PMEA, was synthesized by reversible-addition
      fragmentation chain transfer polymerization (RAFT). The PMEA block contained a
      polymethacrylamide backbone and twin ortho ester rings in the side-chains. At
      neutral pH, PEG-b-PMEA self-assembled to form stable micelles. At pH 5, the twin
      ortho ester rings were quickly hydrolyzed to completion in 12 h, and releasing
      nearly 70% of the encapsulated Nile Red dye. The PEG-b-PMEA micelles were
      completely nontoxic to cultured cells as determined by the MTT assay. Paclitaxel
      (PTX)-loaded micelles showed toxicity toward lung cancer cells comparable to that
      of the free PTX at equivalent doses. These results suggest that the PEG-b-PMEA
      micelles could be useful nano-carriers for pH-responsive delivery of poorly
      soluble anticancer drugs. 

PMID- 25371163
TI  - Assembly, postsynthetic modification and hepatocyte targeting by multiantennary,
      galactosylated soft structures.
AB  - Enzyme modifiable, hollow self-assembled structures offer an excellent scope for
      multiantennary delivery vectors. Herein, we report synthesis and applications of
      bis-galactose lysine based supramolecular ensembles, which possess surface
      galactose moieties amenable to enzymatic modifications. This post-synthetic
      modification generates reactive aldehyde groups, which could possibly serve as
      dynamic anchors for crosslinking and cell adhesion. 

PMID- 25371164
TI  - Mouth cancer awareness and beliefs among dental patients.
AB  - OBJECTIVES: The aim of the present study was to assess the levels of awareness,
      knowledge about signs and risk factors of mouth (oral) cancer, and attitudes
      towards early diagnosis and treatment among dental outpatients. MATERIAL AND
      METHODS: A total of 1,200 adult outpatients attending dental clinics at the
      University of Jordan Hospital for dental examination and treatment were randomly
      selected to participate in the study. An 18-item pretested close-ended
      questionnaire was used for the study. Descriptive statistics were generated and
      chi-square tests, t-tests, one-way analysis of variance (ANOVA), and Spearman's
      rho test were used to examine differences between groups. RESULTS: Only 45.6% of
      the subjects had heard about oral cancer. Some 66.9% and 33.8%, respectively,
      were able to correctly identify tobacco and alcohol as risk factors. Some 24.1%
      had no knowledge about any signs of oral cancer. Male subjects, smokers, alcohol
      drinkers, older participants (>40 years), and participants with less than a
      university education were significantly less aware, and had much less knowledge,
      of the signs and risk factors of oral cancer (P<0.05). CONCLUSION: Awareness
      about oral cancer among Jordanian dental outpatients is low. These dental
      patients, especially those in high-risk groups for mouth cancer and those of
      lower socio-economic status (SES), are less well informed about the signs and
      risk factors of oral cancer. Interventions to improve public knowledge about oral
      cancer and attitudes towards early diagnosis and treatment are urgently
      indicated.

PMID- 25371165
TI  - Treg/Th17 imbalance in malignant pleural effusion partially predicts poor
      prognosis.
AB  - Accumulating evidence shows that an imbalance in regulatory T cells (Tregs)/T
      helper IL-17-producing cells (Th17) exists in malignant pleural effusion (MPE).
      However, the cause of this phenomenon in MPE and the underlying mechanism remain
      uncertain. The percentages of Tregs and Th17 cells in MPE and parapneumonic
      effusion (PPE) were determined by flow cytometry. Their specific transcription
      factors, forkhead box P3 (FoxP3) and retinoic acid-related orphan receptor gammat
      (RORgammat); related cytokines, interleukin-6 (IL-6), IL-17, IL-10, and
      transforming growth factor-beta1 (TGF-beta1); and chemokines, C-C motif ligand 17
      (CCL17) and CCL20, were analyzed by real-time PCR and ELISA, respectively.
      Compared to patients with PPE, patients with MPE presented a higher percentage of
      Tregs but a lower frequency of Th17 cells. Foxp3 mRNA expression level in the
      cells in the pleural effusion was significantly increased in patients with MPE
      compared to the levels in patients with PPE (MPE vs. PPE: 3.05+/-0.62 vs. 0.52+/
      0.11, p=0.0012). It was also noted that high levels of IL-10, TGF-beta1 and CCL17
      were observed in MPE when compared to PPE (MPE vs. PPE: IL-10, 166.3+/-39.53 vs.
      40.38+/-10.92 pg/ml, p=0.0307; TGF-beta1, 10,720+/-1,274 vs. 1,747+/-293.2 pg/ml,
      p<0.0001; CCL17, 341.1+/-88.22 vs. 119.2+/-19.80 pg/ml, p=0.0427). Furthermore, a
      high ratio of Tregs/Th17 cells in MPE was highly correlated to poor survival. An
      alteration in CCL17 and CCL20 might contribute to the Treg/Th17 imbalance in MPE,
      which partially predicts a poor prognosis in patients with lung cancer.

PMID- 25371166
TI  - Targeting axonal protein synthesis in neuroregeneration and degeneration.
AB  - Localized protein synthesis is a mechanism by which morphologically polarized
      cells react in a spatially confined and temporally acute manner to changes in
      their environment. During the development of the nervous system intra-axonal
      protein synthesis is crucial for the establishment of neuronal connections. In
      contrast, mature axons have long been considered as translationally inactive but
      upon nerve injury or under neurodegenerative conditions specific subsets of mRNAs
      are recruited into axons and locally translated. Intra-axonally synthesized
      proteins can have pathogenic or restorative and regenerative functions, and thus
      targeting the axonal translatome might have therapeutic value, for example in the
      treatment of spinal cord injury or Alzheimer's disease. In the case of
      Alzheimer's disease the local synthesis of the stress response transcription
      factor activating transcription factor 4 mediates the long-range retrograde
      spread of pathology across the brain, and inhibition of local Atf4 translation
      downstream of the integrated stress response might interfere with this spread.
      Several molecular tools and approaches have been developed to target specifically
      the axonal translatome by either overexposing proteins locally in axons or,
      conversely, knocking down selectively axonally localized mRNAs. Many questions
      about axonal translation remain to be answered, especially with regard to the
      mechanisms establishing specificity but, nevertheless, targeting the axonal
      translatome is a promising novel avenue to pursue in the development for future
      therapies for various neurological conditions. 

PMID- 25371167
TI  - Phosphodiesterase-4 (PDE4) molecular pharmacology and Alzheimer's disease.
AB  - Between 20% and 25% of patients diagnosed with Alzheimer's disease (AD) do not
      have amyloid burden as assessed by positron emission tomography imaging. Thus,
      there is a need for nonamyloid-directed therapies for AD, especially for those
      patients with non-amyloid AD. The family of phosphodiesterase-4 (PDE4) enzymes
      are underexploited therapeutic targets for central nervous system indications.
      While the PDE4A, B, and D subtypes are expressed in brain, the strict amino acid
      sequence conservation of the active site across the four subtypes of PDE4 has
      made it difficult to discover subtype inhibitors. The recent elucidation of the
      structure of the PDE4 N- and C-terminal regulatory domains now makes it possible
      to design subtype-selective, negative allosteric modulators (PDE4-NAMs). These
      act through closing the N-terminal UCR2 or C-terminal CR3 regulatory domains, and
      thereby inhibit the enzyme by blocking access of cyclic adenosine monophosphate
      (cAMP) to the active site. PDE4B-NAMs have the potential to reduce
      neuroinflammation by dampening microglia cytokine production triggered by brain
      amyloid, while PDE4D-NAMs have potent cognitive benefit by augmenting signaling
      through the cAMP/protein kinase A/cAMP response element-binding protein (CREB)
      pathway for memory consolidation. The importance of PDE4D for human cognition is
      underscored by the recent discovery of PDE4D mutations in acrodysostosis (ACRDY2:
      MIM 600129), an ultra rare disorder associated with intellectual disability.
      Thus, the family of PDE4 enzymes provides rich opportunities for the development
      of mechanistically novel drugs to treat neuroinflammation or the cognitive
      deficits in AD. 

PMID- 25371169
TI  - In vitro comparison of cryopreserved and liquid platelets: potential clinical
      implications.
AB  - BACKGROUND: Platelet (PLT) concentrates can be cryopreserved in dimethyl
      sulfoxide (DMSO) and stored at -80 degrees C for 2 years. These storage
      conditions improve availability in both rural and military environments. Previous
      phenotypic and in vitro studies of cryopreserved PLTs are limited by comparison
      to fresh liquid-stored PLTs, rather than PLTs stored over their clinically
      relevant shelf life. Further, nothing is known of the effect of reconstituting
      cryopreserved PLTs in plasma stored at a variety of clinically relevant
      temperatures. STUDY DESIGN AND METHODS: Apheresis PLTs were either stored at room
      temperature for 5 days or cryopreserved at -80 degrees C with 5% DMSO.
      Cryopreserved PLTs were thawed at 37 degrees C and reconstituted in plasma
      (stored at different temperatures) and compared to fresh and expired liquid
      stored PLTs. In vitro assays were performed to assess glycoprotein expression,
      PLT activity, microparticle content, and function. RESULTS: Compared to liquid
      PLTs over storage, cryopreserved PLTs had reduced expression of the key
      glycoprotein receptors GPIbalpha and GPIIb. However, the proportion of PLTs
      expressing activation markers CD62P and CD63 was similar between cryopreserved
      and liquid-stored PLTs at expiry. Cryopreserved PLT components contained
      significantly higher numbers of phosphatidylserine- and tissue factor-positive
      microparticles than liquid-stored PLTs, and these microparticles reduced the time
      to clot formation and increased thrombin generation. CONCLUSION: There are
      distinct differences between cryopreserved and liquid-stored PLTs. Cryopreserved
      PLTs also have an enhanced hemostatic activity. Knowledge of these in vitro
      differences will be essential to understanding the outcomes of a clinical trial
      comparing cryopreserved PLTs and liquid PLTs stored for various durations.

PMID- 25371170
TI  - Heterogeneous catalytic properties of unprecedented MU-O-[FeTCPP]2 dimers (H2TCPP
      = meso-tetra(4-carboxyphenyl)porphyrin): an unusual superhyperfine EPR structure.
AB  - During the past few years, a great deal of effort has been devoted to the
      anchoring of catalysts into solid coordination networks in order to achieve
      heterogeneous catalysts. In this sense, an innovative approach consists in using
      the coordination-network synthons both as structural units and as catalysts.
      Regarding the latter, metalloporphyrins are suitable candidates for synthons. In
      fact, a few studies report on coordination compounds based on metalloporphyrins
      exhibiting these features. On the other hand, highly distorted di-iron oxo dimers
      containing electron withdrawing groups rank amongst the most effective catalyst
      models. Thus, the aim of this work was to obtain coordination networks based on
      iron porphyrins exhibiting those characteristics. In this way, this work reports
      on the synthesis and characterisation of the MU-O-[FeTCPP]2.16DMF compound
      (H2TCPP = meso-tetra(4-carboxyphenyl)porphyrin, DMF = N,N-dimethylformamide).
      This compound is the first example of a MU-oxo dimer with TCPP. The inter-dimer
      connections give rise to a laminar structure. The structural, spectroscopic and
      magnetic properties of this compound are consistent with the presence of high
      spin Fe(III) ions, exhibiting a strong antiferromagnetic coupling in the MU-oxo
      dimer (J = -132 cm(-1)). An unusual superhyperfine structure has been observed in
      EPR that is related to the high accessible volume of the compound. The structural
      features of the dimers and the accessible network are responsible for the
      excellent behaviour of the compound as a heterogeneous catalyst for different
      oxidations of alcohols. Therefore, this compound is one of the very few examples
      of metalloporphyrins where structural units act as catalysts. 

PMID- 25371168
TI  - beta-Amyloid peptides and amyloid plaques in Alzheimer's disease.
AB  - Many lines of evidence support that beta-amyloid (Abeta) peptides play an
      important role in Alzheimer's disease (AD), the most common cause of dementia.
      But despite much effort the molecular mechanisms of how Abeta contributes to AD
      remain unclear. While Abeta is generated from its precursor protein throughout
      life, the peptide is best known as the main component of amyloid plaques, the
      neuropathological hallmark of AD. Reduction in Abeta has been the major target of
      recent experimental therapies against AD. Unfortunately, human clinical trials
      targeting Abeta have not shown the hoped-for benefits. Thus, doubts have been
      growing about the role of Abeta as a therapeutic target. Here we review evidence
      supporting the involvement of Abeta in AD, highlight the importance of
      differentiating between various forms of Abeta, and suggest that a better
      understanding of Abeta's precise pathophysiological role in the disease is
      important for correctly targeting it for potential future therapy. 

PMID- 25371171
TI  - Impaired mitochondrial function and reduced energy cost as a result of muscle
      damage.
AB  - PURPOSE: Although it has been largely acknowledged that isometric neuromuscular
      electrostimulation (NMES) exercise induces larger muscle damage than voluntary
      contractions, the corresponding effects on muscle energetics remain to be
      determined. Voluntary exercise-induced muscle damage (EIMD) has been reported to
      have minor slight effects on muscle metabolic response to subsequent dynamic
      exercise, but the magnitude of muscle energetics alterations for NMES EIMD has
      never been documented. METHODS: 31P magnetic resonance spectroscopy measurements
      were performed in 13 young healthy males during a standardized rest-exercise
      recovery protocol before (D0) and 2 d (D2) and 4 d (D4) after NMES EIMD on knee
      extensor muscles. Changes in kinetics of phosphorylated metabolite concentrations
      (i.e., phosphocreatine [PCr], inorganic phosphate [Pi], and adenosine
      triphosphate [ATP]) and pH were assessed to investigate aerobic and anaerobic
      rates of ATP production and energy cost of contraction (Ec). RESULTS: Resting
      [Pi]/[PCr] ratio increased at D2 (+39%) and D4 (+29%), mainly owing to the
      increased [Pi] (+43% and +32%, respectively), whereas a significant decrease in
      resting pH was determined (-0.04 pH unit and -0.03 pH unit, respectively). PCr
      recovery rate decreased at D2 (-21%) and D4 (-23%) in conjunction with a
      significantly decreased total rate of ATP production at D4 (-18%) mainly owing to
      an altered aerobic ATP production (-19%). Paradoxically, Ec was decreased at D4 (
      21%). CONCLUSION: Overall, NMES EIMD led to intramuscular acidosis in resting
      muscle and mitochondrial impairment in exercising muscle. Alterations of
      noncontractile processes and/or adaptive mechanisms to muscle damage might
      account for the decreased Ec during the dynamic exercise.

PMID- 25371172
TI  - Conversion of low-affinity peptides to high-affinity peptide binders by using a
      beta-hairpin scaffold-assisted approach.
AB  - Affinity maturation of protein-targeting peptides is generally accomplished by
      homo- or heterodimerization of known peptides. However, applying a
      heterodimerization approach is difficult because it is not clear a priori what
      length or type of linker is required for cooperative binding to a target. Thus,
      an efficient and simple affinity maturation method for converting low-affinity
      peptides into high-affinity peptides would clearly be advantageous for advancing
      peptide-based therapeutics. Here, we describe the development of a novel affinity
      maturation method based on a robust beta-hairpin scaffold and combinatorial phage
      display technology. With this strategy, we were able to increase the affinity of
      existing peptides by more than four orders of magnitude. Taken together, our data
      demonstrate that this scaffold-assisted approach is highly efficient and
      effective in generating high-affinity peptides from their low-affinity
      counterparts. 

PMID- 25371174
TI  - Quetiapine augmentation for depression: dosing pattern in routine practice.
AB  - This study investigated the dosing patterns of quetiapine augmentation (QA) for
      major depressive disorder (MDD) in routine practice. Between 1 January 2009 and
      31 May 2013, patients with a diagnosis of MDD who were receiving QA in
      conjunction with an ongoing antidepressant were recruited into this study. The
      electronic medical records and clinical data for a total of 977 patients were
      reviewed up to a year. Almost half the patients maintained QA treatment for more
      than 3 months. The mean duration of QA was ~6 months, and the mean initial and
      maintenance doses were 23.6 and 40.7 mg/day, respectively (range=12.5-400
      mg/day). The most frequent adverse events observed were somnolence, followed by
      dry mouth and lethargy. Our results indicate that the actual doses of QA for MDD
      in routine practice should be lower than the doses used in placebo-controlled
      clinical trials and those recommended by a regulatory agency. Adequately powered
      and well-controlled prospective studies are needed to better understand the exact
      role of low doses of QA in the treatment of MDD, particularly in routine
      practice.

PMID- 25371173
TI  - Elevated lung cancer in younger adults and low concentrations of arsenic in
      water.
AB  - Arsenic concentrations greater than 100 ug/L in drinking water are a known cause
      of cancer, but the risks associated with lower concentrations are less well
      understood. The unusual geology and good information on past exposure found in
      northern Chile are key advantages for investigating the potential long-term
      effects of arsenic. We performed a case-control study of lung cancer from 2007 to
      2010 in areas of northern Chile that had a wide range of arsenic concentrations
      in drinking water. Previously, we reported evidence of elevated cancer risks at
      arsenic concentrations greater than 100 ug/L. In the present study, we restricted
      analyses to the 92 cases and 288 population-based controls who were exposed to
      concentrations less than 100 ug/L. After adjustment for age, sex, and smoking
      behavior, these exposures from 40 or more years ago resulted in odds ratios for
      lung cancer of 1.00, 1.43 (90% confidence interval: 0.82, 2.52), and 2.01 (90%
      confidence interval: 1.14, 3.52) for increasing tertiles of arsenic exposure,
      respectively (P for trend = 0.02). Mean arsenic water concentrations in these
      tertiles were 6.5, 23.0, and 58.6 ug/L. For subjects younger than 65 years of
      age, the corresponding odds ratios were 1.00, 1.62 (90% confidence interval:
      0.67, 3.90), and 3.41 (90% confidence interval: 1.51, 7.70). Adjustments for
      occupation, fruit and vegetable intake, and socioeconomic status had little
      impact on the results. These findings provide new evidence that arsenic water
      concentrations less than 100 ug/L are associated with higher risks of lung
      cancer.

PMID- 25371175
TI  - Classifying ultra-high risk smoldering myeloma.

PMID- 25371176
TI  - Wild-type KRAS inhibits oncogenic KRAS-induced T-ALL in mice.
AB  - The role of hyperactive RAS signaling is well established in myeloid malignancies
      but less clear in T-cell malignancies. The Kras2(LSL)Mx1-Cre (KM) mouse model
      expresses endogenous KRAS(G12D) in hematopoietic cells and is widely used to
      study mechanisms and treatment of myeloproliferative neoplasms (MPN). The model
      displays an intriguing shift from MPN to acute T-cell leukemia (T-ALL) after
      transplantation to wild-type mice, but the mechanisms underlying this lineage
      shift is unknown. Here, we show that KRAS(G12D) increases proliferation of both
      myeloid and T-cell progenitors, but whereas myeloid cells differentiate, T-cell
      differentiation is inhibited at early stages. Secondary mutations in the expanded
      pool of T-cell progenitors accompany T-ALL development, and our results indicate
      that the shift from myeloid to T-lymphoid malignancy after transplantation is
      explained by the increased likelihood for secondary mutations when the tumor
      lifespan is increased. We demonstrate that tumor lifespan increases after
      transplantation because primary KM mice die rapidly, not from MPN, but from
      KRAS(G12D) expression in nonhematopoietic cells, which causes intestinal bleeding
      and severe anemia. We also identify loss of the wild-type KRAS allele as a
      secondary mutation in all T-ALL cells and provide evidence that wild-type KRAS
      acts as a tumor suppressor in the T-cell lineage in mice. 

PMID- 25371177
TI  - Incidence, risk factors and clinical outcome of leukemia relapses with loss of
      the mismatched HLA after partially incompatible hematopoietic stem cell
      transplantation.
AB  - Genomic loss of the mismatched human leukocyte antigen (HLA) is a recently
      described mechanism of leukemia immune escape and relapse after allogeneic
      hematopoietic stem cell transplantation (HSCT). Here we first evaluated its
      incidence, risk factors and outcome in 233 consecutive transplants from partially
      HLA-mismatched related and unrelated donors (MMRD and MMUD, respectively). We
      documented 84 relapses, 23 of which with HLA loss. All the HLA loss relapses
      occurred after MMRD HSCT, and 20/23 in patients with acute myeloid leukemia. Upon
      MMRD HSCT, HLA loss variants accounted for 33% of the relapses (23/69), occurring
      later than their 'classical' counterparts (median: 307 vs 88 days, P<0.0001).
      Active disease at HSCT increased the risk of HLA loss (hazard ratio (HR): 10.16;
      confidence interval (CI): 2.65-38.92; P=0.001), whereas older patient ages had a
      protective role (HR: 0.16; CI: 0.05-0.46; P=0.001). A weaker association with HLA
      loss was observed for graft T-cell dose and occurrence of chronic graft-versus
      host disease. Outcome after 'classical' and HLA loss relapses was similarly poor,
      and second transplantation from a different donor appeared to provide a slight
      advantage for survival. In conclusion, HLA loss is a frequent mechanism of
      evasion from T-cell alloreactivity and relapse in patients with myeloid
      malignancies transplanted from MMRDs, warranting routine screening in this
      transplantation setting. 

PMID- 25371180
TI  - Cbfb deficiency results in differentiation blocks and stem/progenitor cell
      expansion in hematopoiesis.

PMID- 25371179
TI  - Rapid childhood T-ALL growth in xenograft models correlates with mature phenotype
      and NF-kappaB pathway activation but not with poor prognosis.

PMID- 25371178
TI  - The impact of SF3B1 mutations in CLL on the DNA-damage response.
AB  - Mutations or deletions in TP53 or ATM are well-known determinants of poor
      prognosis in chronic lymphocytic leukemia (CLL), but only account for
      approximately 40% of chemo-resistant patients. Genome-wide sequencing has
      uncovered novel mutations in the splicing factor sf3b1, that were in part
      associated with ATM aberrations, suggesting functional synergy. We first
      performed detailed genetic analyses in a CLL cohort (n=110) containing ATM, SF3B1
      and TP53 gene defects. Next, we applied a newly developed multiplex assay for
      p53/ATM target gene induction and measured apoptotic responses to DNA damage.
      Interestingly, SF3B1 mutated samples without concurrent ATM and TP53 aberrations
      (sole SF3B1) displayed partially defective ATM/p53 transcriptional and apoptotic
      responses to various DNA-damaging regimens. In contrast, NOTCH1 or K/N-RAS
      mutated CLL displayed normal responses in p53/ATM target gene induction and
      apoptosis. In sole SF3B1 mutated cases, ATM kinase function remained intact, and
      gammaH2AX formation, a marker for DNA damage, was increased at baseline and upon
      irradiation. Our data demonstrate that single mutations in sf3b1 are associated
      with increased DNA damage and/or an aberrant response to DNA damage. Together,
      our observations may offer an explanation for the poor prognosis associated with
      SF3B1 mutations. 

PMID- 25371181
TI  - Effects of thyroxine and donepezil on hippocampal acetylcholine content,
      acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in
      hypothyroid adult rats.
AB  - A growing number of studies have revealed that neurocognitive impairment, induced
      by adult-onset hypothyroidism, may not be fully restored by traditional hormone
      substitution therapies, including thyroxine (T4). The present study has
      investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE)
      inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine
      (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1)
      and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05%
      propylthiouracil to their drinking water for five weeks induced hypothyroidism in
      the rat models. From the fourth week, the rats were treated with T4, DON or a
      combination of both. Concentration of ACh and the activity of AChE was determined
      colorimetrically. The results demonstrated that hypothyroidism induced a
      significant decrease of Ach content and AChE activity (by 17 and 34%,
      respectively), which were restored to control values by T4 administration. DON
      treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP
      25 were determined by immunohistochemistry. The results demonstrated that syt-1
      was expressed at significantly lower levels in hypothyroid rats, while SNAP-25
      levels were notably higher compared with the controls. Two-week treatment with T4
      alone failed to normalize the expression levels of these two proteins, while co
      administration of T4 and DON was able to induce this effect. These data suggested
      that the thyroid hormone, T4, may have a direct effect on the metabolism of
      hippocampal ACh in adult rats, and that the DON treatment may facilitate the
      recovery of synaptic protein impairments induced by hypothyroidism. 

PMID- 25371182
TI  - Correlation between diarrhea severity and oocyst count via quantitative PCR or
      fluorescence microscopy in experimental cryptosporidiosis in calves.
AB  - Cryptosporidium is an important diarrhea-associated pathogen, however the
      correlation between parasite burden and diarrhea severity remains unclear. We
      studied this relationship in 10 experimentally infected calves using
      immunofluorescence microscopy and real-time polymerase chain reaction (qPCR) (N =
      124 fecal samples). The qPCR data were corrected for extraction/amplification
      efficiency and gene copy number to generate parasite counts. The qPCR and
      microscopic oocyst quantities exhibited significant correlation (R(2) = 0.33, P <
      0.05), however qPCR had increased sensitivity. Upon comparison with diarrhea
      severity scores (from 0 to 3), a PCR-based count of >= 2.6 * 10(5) parasites or
      an immunofluorescence microscopy count of >= 4.5 * 10(4) oocysts were
      discriminatory predictors of moderate-to-severe diarrhea (versus no-to-mild
      diarrhea), with accuracies and predictive values of 72-82%. In summary, a
      quantitative approach for Cryptosporidium can refine predictive power for
      diarrhea and appears useful for distinguishing clinical cryptosporidiosis versus
      subclinical infection. 

PMID- 25371183
TI  - Surveillance for dengue and dengue-associated neurologic syndromes in the United
      States.
AB  - Autochthonous dengue virus transmission has occurred in the continental United
      States with increased frequency during the last decade; the principal vector,
      Aedes aegypti, has expanded its geographic distribution in the southern United
      States. Dengue, a potentially fatal arboviral disease, is underreported, and US
      clinicians encountering patients with acute febrile illness consistent with
      dengue are likely to not be fully familiar with dengue diagnosis and management.
      Recently, investigators suggested that an outbreak of dengue likely occurred in
      Houston during 2003 based on retrospective laboratory testing of hospitalized
      cases with encephalitis and aseptic meningitis. Although certain aspects of the
      Houston testing results and argument for local transmission are doubtful, the
      report highlights the importance of prospective surveillance for dengue in Aedes
      infested areas of the United States, the need for clinical training on dengue and
      its severe manifestations, and the need for laboratory testing in domestic
      patients presenting with febrile neurologic illness in these regions to include
      dengue. 

PMID- 25371184
TI  - Possible vertical transmission of Bartonella bacilliformis in Peru.
AB  - A 22-day-old male was admitted with a 2-day history of irritability, dyspnea,
      jaundice, fever, and gastrointestinal bleeding. A thin blood smear was performed,
      which showed the presence of intraerythrocyte bacteria identified as Bartonella
      bacilliformis, and subsequently, the child was diagnosed with Carrion's disease.
      The diagnosis was confirmed by specific polymerase chain reaction. The child was
      born in a non-endemic B. bacilliformis area and had not traveled to such an area
      before hospitalization. However, the mother was from an endemic B. bacilliformis
      area, and posterior physical examination showed the presence of a wart compatible
      with B. bacilliformis in semi-immune subjects. These data support vertical
      transmission of B. bacilliformis. 

PMID- 25371185
TI  - Dengue among American missionaries returning from Jamaica, 2012.
AB  - Dengue is an acute febrile illness caused by any of four mosquito-transmitted
      dengue virus (DENV) types. Dengue is endemic in Jamaica, where an epidemic
      occurred in 2012. An investigation was conducted by multiple agencies for 66
      missionaries traveling from nine US states to Jamaica after 1 missionary from the
      group was confirmed to have dengue. Travelers were offered diagnostic testing,
      and a survey was administered to assess knowledge, behaviors, and illness. Of 42
      survey respondents, 9 (21%) respondents reported an acute febrile illness during
      or after travel to Jamaica. Of 15 travelers that provided serum specimens, 4
      (27%) travelers had detectable anti-DENV immunoglobulin M antibody, and 1
      traveler also had DENV-1 detected by reverse transcriptase polymerase chain
      reaction. Recent or past infection with a DENV was evident in 93% (13 of 14)
      missionaries with available sera. No behavioral or demographic factors were
      significantly associated with DENV infection. This investigation shows that even
      trips of short duration to endemic areas present a risk of acquiring dengue. 

PMID- 25371186
TI  - Local evolution of pyrethroid resistance offsets gene flow among Aedes aegypti
      collections in Yucatan State, Mexico.
AB  - The mosquito Aedes aegypti is the major vector of the four serotypes of dengue
      virus (DENV1-4). Previous studies have shown that Ae. aegypti in Mexico have a
      high effective migration rate and that gene flow occurs among populations that
      are up to 150 km apart. Since 2000, pyrethroids have been widely used for
      suppression of Ae. aegypti in cities in Mexico. In Yucatan State in particular,
      pyrethroids have been applied in and around dengue case households creating an
      opportunity for local selection and evolution of resistance. Herein, we test for
      evidence of local adaptation by comparing patterns of variation among 27 Ae.
      aegypti collections at 13 single nucleotide polymorphisms (SNPs): two in the
      voltage-gated sodium channel gene para known to confer knockdown resistance,
      three in detoxification genes previously associated with pyrethroid resistance,
      and eight in putatively neutral loci. The SNPs in para varied greatly in
      frequency among collections, whereas SNPs at the remaining 11 loci showed little
      variation supporting previous evidence for extensive local gene flow. Among Ae.
      aegypti in Yucatan State, Mexico, local adaptation to pyrethroids appears to
      offset the homogenizing effects of gene flow. 

PMID- 25371187
TI  - Evidence of autochthonous Chagas disease in southeastern Texas.
AB  - Autochthonous transmission of Trypanosoma cruzi in the United States is rarely
      reported. Here, we describe five newly identified patients with autochthonously
      acquired infections from a small pilot study of positive blood donors in
      southeast Texas. Case-patients 1-4 were possibly infected near their residences,
      which were all in the same region ~100 miles west of Houston. Case-patient 5 was
      a young male with considerable exposure from routine outdoor and camping
      activities associated with a youth civic organization. Only one of the five
      autochthonous case-patients received anti-parasitic treatment. Our findings
      suggest an unrecognized risk of human vector-borne transmission in southeast
      Texas. Education of physicians and public health officials is crucial for
      identifying the true disease burden and source of infection in Texas. 

PMID- 25371188
TI  - Artemether-lumefantrine compared to atovaquone-proguanil as a treatment for
      uncomplicated Plasmodium falciparum malaria in travelers.
AB  - Atovaquone-proguanil (AP) and artemether-lumefantrine (AL) are both treatments
      for uncomplicated Plasmodium falciparum malaria, but comparative clinical trials
      are lacking. We performed a retrospective analysis, comparing treatment failure
      and fever clearance time in non-immune travelers with uncomplicated P. falciparum
      malaria, treated with AP or AL. Sixty-nine patients were included during 2001
      2013: 44 in the AP group and 25 in the AL group. Treatment failure was observed
      in 6 of 44 (13.6%) and 1 of 25 (4.0%) patients in the AP and AL groups,
      respectively. Six treatment failures were observed in travelers from West Africa.
      Fever clearance time was 44 +/- 23 h in AL group versus 77 +/- 28 h in AP group,
      (P < 0.001). Hospitalization time was significantly shorter in the AL group; 3.8
      + 1.3 versus 5.1 + 2.8 days in the AP group (P = 0.04) In conclusion, travelers
      with uncomplicated P. falciparum malaria recover faster on AL than on AP. The AL
      should probably be the drug of choice for this population. 

PMID- 25371189
TI  - The development and implementation of a competency-based curriculum for training
      in global health research.
AB  - The Fogarty International Center (FIC) Global Health Fellows Program provides
      trainees with the opportunity to develop research skills through a mentored
      research experience, increase their content expertise, and better understand
      trends in global health research, funding organizations, and pathways to generate
      support. The Northern Pacific Global Health Fellows Research and Training
      Consortium, which hosts one of the FIC Global Health Programs, sought to enhance
      research training by developing, implementing, and evaluating a competency-based
      curriculum that uses a modular, asynchronous, web-based format. The curriculum
      has 8 core competencies, 36 learning objectives, and 58 assignments. Nineteen
      trainees completed their 11-month fellowship, engaged in the curriculum, and
      provided pre- and post-fellowship self-assessments. Self-assessed scores
      significantly improved for all competencies. Trainees identified the curriculum
      as one of the strengths of the program. This competency-based curriculum
      represents a first step toward creating a framework of global health research
      competencies on which further efforts could be based. 

PMID- 25371191
TI  - Response to 'Diagnosis of placental mesenchymal dysplasia: magnetic resonance
      imaging or color Doppler?'.

PMID- 25371190
TI  - Renin and the (pro)renin receptor in the renal collecting duct: Role in the
      pathogenesis of hypertension.
AB  - The intrarenal renin-angiotensin system (RAS) plays a critical role in the
      pathogenesis and progression of hypertension and kidney disease. In angiotensin
      (Ang) II-dependent hypertension, collecting duct renin synthesis and secretion
      are stimulated despite suppression of juxtaglomerular (JG) renin. This effect is
      mediated by the AngII type I receptor (AT1 R), independent of blood pressure.
      Although the regulation of JG renin has been extensively studied, the mechanisms
      by which renin is regulated in the collecting duct remain unclear. The
      augmentation of renin synthesis and activity in the collecting duct may provide a
      pathway for additional generation of intrarenal and intratubular AngII formation
      due to the presence of angiotensinogen substrate and angiotensin-converting
      enzyme in the nephron. The recently described (pro)renin receptor ((P)RR) binds
      renin or prorenin, enhancing renin activity and fully activating the biologically
      inactive prorenin peptide. Stimulation of (P)RR also activates intracellular
      pathways related to fibrosis. Renin and the (P)RR are augmented in renal tissues
      of AngII-dependent hypertensive rats. However, the functional contribution of the
      (P)RR to enhanced renin activity in the collecting duct and its contribution to
      the development of hypertension and kidney disease have not been well elucidated.
      This review focuses on recent evidence demonstrating the mechanism of renin
      regulation in the collecting ducts and its interaction with the (P)RR. The data
      suggest that renin-(P)RR interactions may induce stimulation of intracellular
      pathways associated with the development of hypertension and kidney disease. 

PMID- 25371192
TI  - Using ecological indicators and a decision support system for integrated
      ecological assessment at two national park units in the mid-Atlantic region, USA.
AB  - We implemented an integrated ecological assessment using a GIS-based decision
      support system model for Upper Delaware Scenic and Recreational River (UPDE) and
      Delaware Water Gap National Recreation Area (DEWA)-national park units with the
      mid-Atlantic region of the United States. Our assessment examined a variety of
      aquatic and terrestrial indicators of ecosystem components that reflect the
      parks' conservation purpose and reference condition. Our assessment compared
      these indicators to ecological thresholds to determine the condition of park
      watersheds. Selected indicators included chemical and physical measures of water
      quality, biologic indicators of water quality, and landscape condition measures.
      For the chemical and physical measures of water quality, we used a water quality
      index and each of its nine components to assess the condition of water quality in
      each watershed. For biologic measures of water quality, we used the
      Ephemeroptera, Plecoptera, Trichoptera aquatic macroinvertebrate index and,
      secondarily, the Hilsenhoff aquatic macroinvertebrate index. Finally, for the
      landscape condition measures of our model, we used percent forest and percent
      impervious surface. Based on our overall assessment, UPDE and DEWA watersheds had
      an ecological assessment score of 0.433 on a -1 to 1 fuzzy logic scale. This
      score indicates that, in general, the natural resource condition within
      watersheds at these parks is healthy or ecologically unimpaired; however, we had
      only partial data for many of our indicators. Our model is iterative and new data
      may be incorporated as they become available. These natural parks are located
      within a rapidly urbanizing landscape-we recommend that natural resource managers
      remain vigilant to surrounding land uses that may adversely affect natural
      resources within the parks. 

PMID- 25371193
TI  - Local wood demand, land cover change and the state of Albany Thicket on an urban
      commonage in the Eastern Cape, South Africa.
AB  - Understanding the rates and causes of land-use change is crucial in identifying
      solutions, especially in sensitive landscapes and ecosystems, as well as in
      places undergoing rapid political, socioeconomic or ecological change. Despite
      considerable concern at the rate of transformation and degradation of the
      biodiversity-rich Albany Thicket biome in South Africa, most knowledge is gleaned
      from private commercial lands and state conservation areas. In comparison, there
      is limited work in communal areas where land uses include biomass extraction,
      especially for firewood and construction timber. We used aerial photographs to
      analyze land use and cover change in the high- and low-use zones of an urban
      commonage and an adjacent protected area over almost six decades, which included
      a major political transition. Field sampling was undertaken to characterize the
      current state of the vegetation and soils of the commonage and protected area and
      to determine the supply and demand for firewood and construction timber. Between
      the 1950s and 1980s, there was a clear increase in woody vegetation cover, which
      was reversed after the political transition in the mid-1990s. However, current
      woody plant standing stocks and sustainable annual production rates are well
      above current firewood demand, suggesting other probable causes for the decline
      in woody plant cover. The fragmentation of woody plant cover is paralleled by
      increases in grassy areas and bare ground, an increase in soil compaction, and
      decreases in soil moisture, carbon, and nutrients. 

PMID- 25371194
TI  - Using scenario planning to evaluate the impacts of climate change on wildlife
      populations and communities in the Florida Everglades.
AB  - It is uncertain how climate change will impact hydrologic drivers of wildlife
      population dynamics in freshwater wetlands of the Florida Everglades, or how to
      accommodate this uncertainty in restoration decisions. Using projections of
      climate scenarios for the year 2060, we evaluated how several possible futures
      could affect wildlife populations (wading birds, fish, alligators, native apple
      snails, amphibians, threatened and invasive species) across the Everglades
      landscape and inform planning already underway. We used data collected from prior
      research and monitoring to parameterize our wildlife population models.
      Hydrologic data were simulated using a spatially explicit, regional-scale model.
      Our scenario evaluations show that expected changes in temperature,
      precipitation, and sea level could significantly alter important ecological
      functions. All of our wildlife indicators were negatively affected by scenarios
      with less rainfall and more evapotranspiration. Under such scenarios, habitat
      suitability was substantially reduced for iconic animals such as wading birds and
      alligators. Conversely, the increased rainfall scenario benefited aquatic prey
      productivity and apex predators. Cascading impacts on non-native species is
      speculative, but increasing temperatures could increase the time between cold
      events that currently limit expansion and abundance of non-native fishes,
      amphibians, and reptiles with natural ranges in the tropics. This scenario
      planning framework underscored the benefits of proceeding with Everglades
      restoration plans that capture and clean more freshwater with the potential to
      mitigate rainfall loss and postpone impacts of sea level rise. 

PMID- 25371195
TI  - Wolfram syndrome 2: a novel CISD2 mutation identified in Italian siblings.

PMID- 25371196
TI  - Occurrence of an unusual hopanoid-containing lipid A among lipopolysaccharides
      from Bradyrhizobium species.
AB  - The chemical structures of the unusual hopanoid-containing lipid A samples of the
      lipopolysaccharides (LPS) from three strains of Bradyrhizobium (slow-growing
      rhizobia) have been established. They differed considerably from other Gram
      negative bacteria in regards to the backbone structure, the number of ester
      linked long chain hydroxylated fatty acids, as well as the presence of a tertiary
      residue that consisted of at least one molecule of carboxyl-bacteriohopanediol or
      its 2-methyl derivative. The structural details of this type of lipid A were
      established using one- and two-dimensional NMR spectroscopy, chemical composition
      analyses, and mass spectrometry techniques (electrospray ionization Fourier
      transform ion cyclotron resonance mass spectrometry and MALDI-TOF-MS). In these
      lipid A samples the glucosamine disaccharide characteristic for enterobacterial
      lipid A was replaced by a 2,3-diamino-2,3-dideoxy-d-glucopyranosyl-(GlcpN3N)
      disaccharide, deprived of phosphate residues, and substituted by an alpha-d-Manp
      (1->6)-alpha-d-Manp disaccharide substituting C-4' of the non-reducing (distal)
      GlcpN3N, and one residue of galacturonic acid (d-GalpA) alpha-(1->1)-linked to
      the reducing (proximal) amino sugar residue. Amide-linked 12:0(3-OH) and 14:0(3
      OH) were identified. Some hydroxy groups of these fatty acids were further
      esterified by long (omega-1)-hydroxylated fatty acids comprising 26-34 carbon
      atoms. As confirmed by mass spectrometry techniques, these long chain fatty acids
      could form two or three acyloxyacyl residues. The triterpenoid derivatives were
      identified as 34-carboxyl-bacteriohopane-32,33-diol and 34-carboxyl-2beta-methyl
      bacteriohopane-32,33-diol and were covalently linked to the (omega-1)-hydroxy
      group of very long chain fatty acid in bradyrhizobial lipid A. Bradyrhizobium
      japonicum possessed lipid A species with two hopanoid residues. 

PMID- 25371197
TI  - TAK1-ECSIT-TRAF6 complex plays a key role in the TLR4 signal to activate NF
      kappaB.
AB  - ECSIT (evolutionarily conserved signaling intermediate in Toll pathways) is known
      as a multifunctional regulator in different signals, including Toll-like
      receptors (TLRs), TGF-beta, and BMP. Here, we report a new regulatory role of
      ECSIT in TLR4-mediated signal. By LPS stimulation, ECSIT formed a high molecular
      endogenous complex including TAK1 and TRAF6, in which ECSIT interacted with each
      protein and regulated TAK1 activity, leading to the activation of NF-kappaB.
      ECSIT-knockdown THP-1 (ECSIT(KD) THP-1) cells exhibited severe impairments in NF
      kappaB activity, cytokine production, and NF-kappaB-dependent gene expression,
      whereas those were dramatically restored by reintroduction of wild type (WT)
      ECSIT gene. Interestingly, ECSIT mutants, which lack a specific interacting
      domain for either TAK1 or TRAF6, could not restore these activities. Moreover, no
      significant changes in both NF-kappaB activity and cytokine production induced by
      TLR4 could be seen in TAK1(KD) or TRAF6(KD) THP-1 cells transduced by WT ECSIT,
      strongly suggesting the essential requirement of TAK1-ECSIT-TRAF6 complex in TLR4
      signaling. Taken together, our data demonstrate that the ECSIT complex, including
      TAK1 and TRAF6, plays a pivotal role in TLR4-mediated signals to activate NF
      kappaB. 

PMID- 25371198
TI  - Activation of calcium- and voltage-gated potassium channels of large conductance
      by leukotriene B4.
AB  - Calcium/voltage-gated, large conductance potassium (BK) channels control numerous
      physiological processes, including myogenic tone. BK channel regulation by direct
      interaction between lipid and channel protein sites has received increasing
      attention. Leukotrienes (LTA4, LTB4, LTC4, LTD4, and LTE4) are inflammatory lipid
      mediators. We performed patch clamp studies in Xenopus oocytes that co-expressed
      BK channel-forming (cbv1) and accessory beta1 subunits cloned from rat cerebral
      artery myocytes. Leukotrienes were applied at 0.1 nm-10 MUm to either leaflet of
      cell-free membranes at a wide range of [Ca(2+)]i and voltages. Only LTB4
      reversibly increased BK steady-state activity (EC50 = 1 nm; Emax reached at 10
      nm), with physiological [Ca(2+)]i and voltages favoring this activation.
      Homomeric cbv1 or cbv1-beta2 channels were LTB4-resistant. Computational modeling
      predicted that LTB4 docked onto the cholane steroid-sensing site in the BK beta1
      transmembrane domain 2 (TM2). Co-application of LTB4 and cholane steroid did not
      further increase LTB4-induced activation. LTB4 failed to activate beta1 subunit
      containing channels when beta1 carried T169A, A176S, or K179I within the docking
      site. Co-application of LTB4 with LTA4, LTC4, LTD4, or LTE4 suppressed LTB4
      induced activation. Inactive leukotrienes docked onto a portion of the site,
      probably preventing tight docking of LTB4. In summary, we document the ability of
      two endogenous lipids from different chemical families to share their site of
      action on a channel accessory subunit. Thus, cross-talk between leukotrienes and
      cholane steroids might converge on regulation of smooth muscle contractility via
      BK beta1. Moreover, the identification of LTB4 as a highly potent ligand for BK
      channels is critical for the future development of beta1-specific BK channel
      activators. 

PMID- 25371200
TI  - MicroRNA-200 (miR-200) cluster regulation by achaete scute-like 2 (Ascl2): impact
      on the epithelial-mesenchymal transition in colon cancer cells.
AB  - Ascl2, a basic helix-loop-helix transcription factor, is a downstream target of
      WNT signaling that controls the fate of intestinal cryptic stem cells and colon
      cancer progenitor cells. However, its involvement in colon cancer and downstream
      molecular events is largely undefined; in particular, the mechanism by which
      Ascl2 regulates the plasticity of epithelial-mesenchymal transition (EMT) and
      mesenchymal-epithelial transition (MET) programs in colon cancer cells remains
      unknown. In this study, we systematically demonstrate that Ascl2 loss of function
      in colon cancer cells promotes MET by derepressing the expression of microRNA
      (miR)-200s (i.e. miR-200b, miR-200a, miR-429, miR-200c, and miR-141) and further
      activating their expression through a transcriptional mechanism that involves
      direct binding to the most proximal E-box (E-box2) in the miR-200b-a-429
      promoter. Activation of miR-200s due to Ascl2 deficiency led to the inhibition of
      ZEB1/2 expression and the alteration of epithelial and mesenchymal features.
      Transfection of miR-200b, miR-200a, and miR-429 inhibitors into Ascl2-deficient
      colon cancer cells promoted the epithelial-mesenchymal transition in a reversible
      manner. Transfection of miR-200a or miR-429 inhibitors into Ascl2-deficient colon
      cancer cells increased cellular proliferation and migration. Ascl2 mRNA levels
      and the miR-200a, miR-200b, miR-200c, miR-141, or miR-429 levels in the colon
      cancerous samples were inversely correlated. These results provide the first
      evidence of a link between Ascl2 and miR-200s in the regulation of EMT-MET
      plasticity in colon cancer. 

PMID- 25371199
TI  - Evaluating the capacity to generate and preserve nitric oxide bioactivity in
      highly purified earthworm erythrocruorin: a giant polymeric hemoglobin with
      potential blood substitute properties.
AB  - The giant extracellular hemoglobin (erythrocruorin) from the earth worm
      (Lumbricus terrestris) has shown promise as a potential hemoglobin-based oxygen
      carrier (HBOC) in in vivo animal studies. An important beneficial characteristic
      of this hemoglobin (LtHb) is the large number of heme-based oxygen transport
      sites that helps overcome issues of osmotic stress when attempting to provide
      enough material for efficient oxygen delivery. A potentially important additional
      property is the capacity of the HBOC either to generate nitric oxide (NO) or to
      preserve NO bioactivity to compensate for decreased levels of NO in the
      circulation. The present study compares the NO-generating and NO bioactivity
      preserving capability of LtHb with that of human adult hemoglobin (HbA) through
      several reactions including the nitrite reductase, reductive nitrosylation, and
      still controversial nitrite anhydrase reactions. An assignment of a heme-bound
      dinitrogen trioxide as the stable intermediate associated with the nitrite
      anhydrase reaction in both LtHb and HbA is supported based on functional and EPR
      spectroscopic studies. The role of the redox potential as a factor contributing
      to the NO-generating activity of these two proteins is evaluated. The results
      show that LtHb undergoes the same reactions as HbA and that the reduced efficacy
      for these reactions for LtHb relative to HbA is consistent with the much higher
      redox potential of LtHb. Evidence of functional heterogeneity in LtHb is
      explained in terms of the large difference in the redox potential of the isolated
      subunits. 

PMID- 25371201
TI  - Hes3 is expressed in the adult pancreatic islet and regulates gene expression,
      cell growth, and insulin release.
AB  - The transcription factor Hes3 is a component of a signaling pathway that supports
      the growth of neural stem cells with profound consequences in neurodegenerative
      disease models. Here we explored whether Hes3 also regulates pancreatic islet
      cells. We showed that Hes3 is expressed in human and rodent pancreatic islets. In
      mouse islets it co-localizes with alpha and beta cell markers. We employed the
      mouse insulinoma cell line MIN6 to perform in vitro characterization and
      functional studies in conditions known to modulate Hes3 based upon our previous
      work using neural stem cell cultures. In these conditions, cells showed elevated
      Hes3 expression and nuclear localization, grew efficiently, and showed higher
      evoked insulin release responses, compared with serum-containing conditions. They
      also exhibited higher expression of the transcription factor Pdx1 and insulin.
      Furthermore, they were responsive to pharmacological treatments with the GLP-1
      analog Exendin-4, which increased nuclear Hes3 localization. We employed a
      transfection approach to address specific functions of Hes3. Hes3 RNA
      interference opposed cell growth and affected gene expression as revealed by DNA
      microarrays. Western blotting and PCR approaches specifically showed that Hes3
      RNA interference opposes the expression of Pdx1 and insulin. Hes3 overexpression
      (using a Hes3-GFP fusion construct) confirmed a role of Hes3 in regulating Pdx1
      expression. Hes3 RNA interference reduced evoked insulin release. Mice lacking
      Hes3 exhibited increased islet damage by streptozotocin. These data suggest roles
      of Hes3 in pancreatic islet function. 

PMID- 25371203
TI  - Functional characterization of 5-oxoproline transport via SLC16A1/MCT1.
AB  - Thyrotropin-releasing hormone is a tripeptide that consists of 5-oxoproline,
      histidine, and proline. The peptide is rapidly metabolized by various enzymes. 5
      Oxoproline is produced by enzymatic hydrolysis in a variety of peptides. Previous
      studies showed that 5-oxoproline could become a possible biomarker for autism
      spectrum disorders. Here we demonstrate the involvement of SLC16A1 in the
      transport of 5-oxoproline. An SLC16A1 polymorphism (rs1049434) was recently
      identified. However, there is no information about the effect of the polymorphism
      on SLC16A1 function. In this study, the polymorphism caused an observable change
      in 5-oxoproline and lactate transport via SLC16A1. The Michaelis constant (Km)
      was increased in an SLC16A1 mutant compared with that in the wild type. In
      addition, the proton concentration required to produce half-maximal activation of
      transport activity (K0.5, H (+)) was increased in the SLC16A1 mutant compared
      with that in the wild type. Furthermore, we examined the transport of 5
      oxoproline in T98G cells as an astrocyte cell model. Despite the fact that 5
      oxoproline is an amino acid derivative, Na(+)-dependent and amino acid transport
      systems scarcely contributed to 5-oxoproline transport. Based on our findings, we
      conclude that H(+)-coupled 5-oxoproline transport is mediated solely by SLC16A1
      in the cells. 

PMID- 25371202
TI  - Mechanism of multivalent nanoparticle encounter with HIV-1 for potency
      enhancement of peptide triazole virus inactivation.
AB  - Entry of HIV-1 into host cells remains a compelling yet elusive target for
      developing agents to prevent infection. A peptide triazole (PT) class of entry
      inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions
      of the Env protein at host cell receptor binding sites, inhibit cell infection,
      and cause envelope spike protein breakdown, including gp120 shedding and, for
      some variants, virus membrane lysis. We found that gold nanoparticle-conjugated
      forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral
      effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought
      to reveal the mechanism of potency enhancement underlying nanoparticle conjugate
      function. We found that altering the physical properties of the nanoparticle
      conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on
      the AuNP surface, enhanced potency of infection inhibition to impressive
      picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less
      susceptible to reduction of antiviral potency when the density of PT-competent
      Env spikes on the virus was reduced by incorporating a peptide-resistant mutant
      gp120. We conclude that potency enhancement of virolytic activity and
      corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation
      derives from multivalent contact between the nanoconjugates and metastable Env
      spikes on the HIV-1 virus. The findings reveal that multispike engagement can
      exploit the metastability built into virus the envelope to irreversibly
      inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based
      antiviral agents for HIV-1 specifically and putatively for metastable enveloped
      viruses generally. 

PMID- 25371204
TI  - The anti-proliferative function of the TGF-beta1 signaling pathway involves the
      repression of the oncogenic TBX2 by its homologue TBX3.
AB  - A growing body of work has shown that the highly homologous T-box transcription
      factors TBX2 and TBX3 play critical but distinct roles in embryonic development
      and cancer progression. For example, TBX2 and TBX3 are up-regulated in several
      cancers and recent evidence suggests that whereas TBX2 functions as a pro
      proliferative factor, TBX3 inhibits cell proliferation but promotes cancer cell
      migration and invasion. While the molecular mechanisms regulating these functions
      of TBX2 and TBX3 are poorly understood we recently reported that the TGF-beta1
      signaling pathway up-regulates TBX3 expression to mediate, in part, its well
      described anti-proliferative and pro-migratory roles. The TBX3 targets
      responsible for these functions were however not identified. Here we reveal for
      the first time that the TGF-beta1 signaling pathway represses TBX2
      transcriptionally and we provide a detailed mechanism to show that this is
      mediated by TBX3. Furthermore, we implicate the down-regulation of TBX2 in the
      anti-proliferative function of the TGF-beta1-TBX3 axis. These findings have
      important implications for our understanding of the regulation of TBX2 and TBX3
      and shed light on the mechanisms involved in the anti-proliferative and pro
      migratory roles of TGF-beta1. 

PMID- 25371205
TI  - Structure-function analysis of heterodimer formation, oligomerization, and
      receptor binding of the Staphylococcus aureus bi-component toxin LukGH.
AB  - The bi-component leukocidins of Staphylococcus aureus are important virulence
      factors that lyse human phagocytic cells and contribute to immune evasion. The
      gamma-hemolysins (HlgAB and HlgCB) and Panton-Valentine leukocidin (PVL or LukSF)
      were shown to assemble from soluble subunits into membrane-bound oligomers on the
      surface of target cells, creating barrel-like pore structures that lead to cell
      lysis. LukGH is the most distantly related member of this toxin family, sharing
      only 30-40% amino acid sequence identity with the others. We observed that,
      unlike other leukocidin subunits, recombinant LukH and LukG had low solubility
      and were unable to bind to target cells, unless both components were present.
      Using biolayer interferometry and intrinsic tryptophan fluorescence we detected
      binding of LukH to LukG in solution with an affinity in the low nanomolar range
      and dynamic light scattering measurements confirmed formation of a heterodimer.
      We elucidated the structure of LukGH by x-ray crystallography at 2.8-A
      resolution. This revealed an octameric structure that strongly resembles that
      reported for HlgAB, but with important structural differences. Structure guided
      mutagenesis studies demonstrated that three salt bridges, not found in other bi
      component leukocidins, are essential for dimer formation in solution and receptor
      binding. We detected weak binding of LukH, but not LukG, to the cellular receptor
      CD11b by biolayer interferometry, suggesting that in common with other members of
      this toxin family, the S-component has the primary contact role with the
      receptor. These new insights provide the basis for novel strategies to counteract
      this powerful toxin and Staphylococcus aureus pathogenesis. 

PMID- 25371207
TI  - Role of small subunit in mediating assembly of red-type form I Rubisco.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the key enzyme
      involved in photosynthetic carbon fixation, converting atmospheric CO2 to organic
      compounds. Form I Rubisco is a cylindrical complex composed of eight large (RbcL)
      subunits that are capped by four small subunits (RbcS) at the top and four at the
      bottom. Form I Rubiscos are phylogenetically divided into green- and red-type.
      Some red-type enzymes have catalytically superior properties. Thus, understanding
      their folding and assembly is of considerable biotechnological interest. Folding
      of the green-type RbcL subunits in cyanobacteria is mediated by the GroEL/ES
      chaperonin system, and assembly to holoenzyme requires specialized chaperones
      such as RbcX and RAF1. Here, we show that the red-type RbcL subunits in the
      proteobacterium Rhodobacter sphaeroides also fold with GroEL/ES. However,
      assembly proceeds in a chaperone-independent manner. We find that the C-terminal
      beta-hairpin extension of red-type RbcS, which is absent in green-type RbcS, is
      critical for efficient assembly. The beta-hairpins of four RbcS subunits form an
      eight-stranded beta-barrel that protrudes into the central solvent channel of the
      RbcL core complex. The two beta-barrels stabilize the complex through multiple
      interactions with the RbcL subunits. A chimeric green-type RbcS carrying the C
      terminal beta-hairpin renders the assembly of a cyanobacterial Rubisco
      independent of RbcX. Our results may facilitate the engineering of crop plants
      with improved growth properties expressing red-type Rubisco. 

PMID- 25371206
TI  - The functional differences between pro-survival and pro-apoptotic B cell lymphoma
      2 (Bcl-2) proteins depend on structural differences in their Bcl-2 homology 3
      (BH3) domains.
AB  - Bcl-2 homology 3 (BH3) domains are short sequence motifs that mediate nearly all
      protein-protein interactions between B cell lymphoma 2 (Bcl-2) family proteins in
      the intrinsic apoptotic cell death pathway. These sequences are found on both pro
      survival and pro-apoptotic members, although their primary function is believed
      to be associated with induction of cell death. Here, we identify critical
      features of the BH3 domains of pro-survival proteins that distinguish them
      functionally from their pro-apoptotic counterparts. Biochemical and x-ray
      crystallographic studies demonstrate that these differences reduce the capacity
      of most pro-survival proteins to form high affinity "BH3-in-groove" complexes
      that are critical for cell death induction. Switching these residues for the
      corresponding residues in Bcl-2 homologous antagonist/killer (Bak) increases the
      binding affinity of isolated BH3 domains for pro-survival proteins; however,
      their exchange in the context of the parental protein causes rapid proteasomal
      degradation due to protein destabilization. This is supported by further x-ray
      crystallographic studies that capture elements of this destabilization in one pro
      survival protein, Bcl-w. In pro-apoptotic Bak, we demonstrate that the
      corresponding distinguishing residues are important for its cell-killing capacity
      and antagonism by pro-survival proteins. 

PMID- 25371208
TI  - A juvenile hormone transcription factor Bmdimm-fibroin H chain pathway is
      involved in the synthesis of silk protein in silkworm, Bombyx mori.
AB  - The genes responsible for silk biosynthesis are switched on and off at particular
      times in the silk glands of Bombyx mori. This switch appears to be under the
      control of endogenous and exogenous hormones. However, the molecular mechanisms
      by which silk protein synthesis is regulated by the juvenile hormone (JH) are
      largely unknown. Here, we report a basic helix-loop-helix transcription factor,
      Bmdimm, its silk gland-specific expression, and its direct involvement in the
      regulation of fibroin H-chain (fib-H) by binding to an E-box (CAAATG) element of
      the fib-H gene promoter. Far-Western blots, enzyme-linked immunosorbent assays,
      and co-immunoprecipitation assays revealed that Bmdimm protein interacted with
      another basic helix-loop-helix transcription factor, Bmsage. Immunostaining
      revealed that Bmdimm and Bmsage proteins are co-localized in nuclei. Bmdimm
      expression was induced in larval silk glands in vivo, in silk glands cultured in
      vitro, and in B. mori cell lines after treatment with a JH analog. The JH effect
      on Bmdimm was mediated by the JH-Met-Kr-h1 signaling pathway, and Bmdimm
      expression did not respond to JH by RNA interference with double-stranded BmKr-h1
      RNA. These data suggest that the JH regulatory pathway, the transcription factor
      Bmdimm, and the targeted fib-H gene contribute to the synthesis of fibroin H
      chain protein in B. mori. 

PMID- 25371209
TI  - MUC1 protein induces urokinase-type plasminogen activator (uPA) by forming a
      complex with NF-kappaB p65 transcription factor and binding to the uPA promoter,
      leading to enhanced invasiveness of cancer cells.
AB  - Mucin 1 (MUC1) is overexpressed in various human malignant tumors and its
      expression is correlated with a poor prognosis. MUC1 engages in signal
      transduction by interacting with receptors for growth and differentiation
      factors, which contributes to the growth and survival of cancer cells. However,
      the mechanism by which MUC1 promotes cancer cell invasion remains unclear.
      Microarray analysis revealed that expression of urokinase-type plasminogen
      activator (uPA) was elevated in MUC1-overexpressing cells. Furthermore, up- and
      down-modulation of MUC1 expression was clearly correlated with the change of uPA
      expression. An immunochemical study showed that the distribution of uPA coincided
      with that of MUC1 in various human cancer tissues. The MUC1 C-terminal domain
      (MUC1-CD) was associated with nuclear factor-kappaB (NF-kappaB) p65 in MUC1
      expressing cells. Chromatin immunoprecipitation (ChIP) assays demonstrated that
      MUC1-CD existed with NF-kappaB p65 on the uPA promoter. Luciferase assays
      indicated that the uPA transcriptional activity was correlated with the level of
      MUC1 expression and that this MUC1-enhancing effect on the uPA transcription was
      abolished by introduction of mutations into the NF-kappaB binding sites on the
      uPA promoter. These results indicate that formation of the MUC1-CD and NF-kappaB
      p65 complex enhanced nuclear translocation of NF-kappaB p65 and subsequent
      occupancy of NF-kappaB binding region on the uPA promoter, leading to elevated
      transcription of uPA. We also demonstrated that uPA induced by MUC1 enhanced the
      matrix metalloproteinase (MMP)-2 and -9 activities, and consequently promoted
      cancer cell invasion. Thus, a MUC1 co-operating NF-kappaB signaling pathway plays
      a critical role in cancer cell invasion in MUC1-expressing cells. 

PMID- 25371210
TI  - Dendritic cell IL-1alpha and IL-1beta are polyubiquitinated and degraded by the
      proteasome.
AB  - IL-1alpha and beta are key players in the innate immune system. The secretion of
      these cytokines by dendritic cells (DC) is integral to the development of
      proinflammatory responses. These cytokines are not secreted via the classical
      secretory pathway. Instead, 2 independent processes are required; an initial
      signal to induce up-regulation of the precursor pro-IL-1alpha and -beta, and a
      second signal to drive cleavage and consequent secretion. Pro-IL-1alpha and -beta
      are both cytosolic and thus, are potentially subject to post-translational
      modifications. These modifications may, in turn, have a functional outcome in the
      context of IL-1alpha and -beta secretion and hence inflammation. We report here
      that IL-1alpha and -beta were degraded intracellularly in murine bone marrow
      derived DC and that this degradation was dependent on active cellular processes.
      In addition, we demonstrate that degradation was ablated when the proteasome was
      inhibited, whereas autophagy did not appear to play a major role. Furthermore,
      inhibition of the proteasome led to an accumulation of polyubiquitinated IL
      1alpha and -beta, indicating that IL-1alpha and -beta were polyubiquitinated
      prior to proteasomal degradation. Finally, our investigations suggest that
      polyubiquitination and proteasomal degradation are not continuous processes but
      instead are up-regulated following DC activation. Overall, these data highlight
      that IL-1alpha and -beta polyubiquitination and proteasomal degradation are
      central mechanisms in the regulation of intracellular IL-1 levels in DC. 

PMID- 25371211
TI  - Non-canonical interleukin 23 receptor complex assembly: p40 protein recruits
      interleukin 12 receptor beta1 via site II and induces p19/interleukin 23 receptor
      interaction via site III.
AB  - IL-23, composed of the cytokine subunit p19 and the soluble alpha receptor
      subunit p40, binds to a receptor complex consisting of the IL-23 receptor (IL
      23R) and the IL-12 receptor beta1 (IL-12Rbeta1). Complex formation was
      hypothesized to follow the "site I-II-III" architectural paradigm, with site I of
      p19 being required for binding to p40, whereas sites II and III of p19 mediate
      binding to IL-12Rbeta1 and IL-23R, respectively. Here we show that the binding
      mode of p19 to p40 and of p19 to IL-23R follow the canonical site I and III
      paradigm but that interaction of IL-23 to IL-12Rbeta1 is independent of site II
      in p19. Instead, binding of IL-23 to the cytokine binding module of IL-12Rbeta1
      is mediated by domains 1 and 2 of p40 via corresponding site II amino acids of IL
      12Rbeta1. Moreover, domains 2 and 3 of p40 were sufficient for complex formation
      with p19 and to induce binding of p19 to IL-23R. The Fc-tagged fusion protein of
      p40_D2D3/p19 did, however, not act as a competitive IL-23 antagonist but, at
      higher concentrations, induced proliferation via IL-23R but independent of IL
      12Rbeta1. On the basis of our experimental validation, we propose a non-canonical
      topology of the IL-23.IL-23R.IL-12Rbeta1 complex. Furthermore, our data help to
      explain why p40 is an antagonist of IL-23 and IL-12 signaling and show that site
      II of p19 is dispensable for IL-23 signaling. 

PMID- 25371212
TI  - Kinetics of iron import into developing mouse organs determined by a pup-swapping
      method.
AB  - The kinetics of dietary iron import into various organs of mice were evaluated
      using a novel pup-swapping approach. Newborn pups whose bodies primarily
      contained (56)Fe or (57)Fe were swapped at birth such that each nursed on milk
      containing the opposite isotope. A pup from each litter was euthanized weekly
      over a 7-week period. Blood plasma was obtained, and organs were isolated
      typically after flushing with Ringer's buffer. (56)Fe and (57)Fe concentrations
      were determined for organs and plasma; organ volumes were also determined.
      Mossbauer spectra of equivalent (57)Fe-enriched samples were used to quantify
      residual blood in organs; this fraction was excluded from later analysis. Rates
      of import into brain, spleen, heart, and kidneys were highest during the first 2
      weeks of life. In contrast, half of iron in the newborn liver exited during that
      time, and influx peaked later. Two mathematical models were developed to analyze
      the import kinetics. The only model that simulated the data adequately assumed
      that an iron-containing species enters the plasma and converts into a second
      species and that both are independently imported into organs. Consistent with
      this, liquid chromatography with an on-line ICP-MS detector revealed numerous
      iron species in plasma besides transferrin. Model fitting required that the first
      species, assigned to non-transferrin-bound iron, imports faster into organs than
      the second, assigned to transferrin-bound-iron. Non-transferrin-bound iron rather
      than transferrin-bound-iron appears to play the dominant role in importing iron
      into organs during early development of healthy mice. 

PMID- 25371214
TI  - A qualitative study of smoking behavior among the floating population in
      Shanghai, China.
AB  - BACKGROUND: China has become the world's largest producer and consumer of tobacco
      and lung cancer is China's leading cause of cancer deaths. The large majority of
      Chinese smokers are men. Tobacco consumption is of particular concern among
      China's internal floating (or migrant) population, which has become a permanent
      feature of Chinese society, because this population is very large (over 100
      million persons) and it has a high prevalence of smoking. Considering
      additionally that like the general population of China, the smoking prevalence
      rate of women from this group is quite low, we therefore aimed to explore smoking
      related knowledge, attitudes and behaviours among male smokers in the floating
      population to help inform the development of effective smoking cessation
      interventions in this important target group in China. METHODS: We interviewed 39
      floating population male smokers in six focus groups and performed a qualitative
      content analysis of the interviews. RESULTS: Most participants knew that smoking
      is risky to health but they knew little about why. Habit and social participation
      were key drivers of smoking. Smoking was regarded as a core component of their
      identity by the urban residents. Some participants had tried to stop smoking but
      none reported having ever been educated about smoking. CONCLUSIONS: Smoking
      cessation interventions for China's male floating population would need to
      incorporate comprehensive education and information about why smoking is
      dangerous and the benefits of stopping.

PMID- 25371215
TI  - Effects of vanadium (V) and magnesium (Mg) on rat bone tissue: mineral status and
      micromorphology. Consequences of V-Mg interactions.
AB  - The extent to which the 12 week separate and combined administration of vanadium
      (as sodium metavanadate--SMV, 0.125 mg V per ml) and magnesium (as magnesium
      sulphate--MS, 0.06 mg Mg per ml) affects bone mineral status and micromorphology
      as well as the alkaline phosphatase (ALP) activity in femoral diaphysis (FD) was
      examined in male rats. The bone chemical composition of SMV-exposed rats was also
      investigated. SMV alone or in combination with MS (as SMV-MS) reduced the levels
      of MgFD (by 21% and 20%) and PFD (by 12% and 9%), lowered the CaFD content (by 7%
      and 10%), and caused a rise of the FeFD concentration (by 22.5% and 17%),
      compared with the control; SMV alone also reduced and enhanced the KFD and ZnFD
      concentrations (by 19% and 15%, respectively) but remained without significant
      effect on the femoral bone surface roughness (FBSR), whereas MS alone lowered the
      VFD, PFD, and CuFD levels (by 42%, 10%, and 20.6%), reduced FBSR, and created the
      regular femoral bone surface shape. The SMV-MS combination also induced a decline
      and rise in the levels of CuFD (by 30%) and NaFD (by 15%), respectively, compared
      with the control and the MS-supplemented rats; elevated ALPFD activity (by 24%,
      35%, and 40%), compared with the control, SMV-exposed, and MS-supplemented
      animals; and increased FBSR. Relationships between the root mean square roughness
      (Sq) and skewness (Ssk): Sq [MS < SMV < Control < SMV-MS] <=> Ssk [SMV-MS >
      Control > SMV > MS], ALPFD and Sq: ALPFD<=> Sq [SMV-MS > Control > SMV > MS], and
      between other variables were demonstrated. A partial limitation of the drop in
      the PFD and KFD levels and normalization of the ZnFD concentration were a
      consequence of the V-Mg antagonistic interaction whereas a consequence of the V
      Mg synergistic interaction was the increase in the NaFD level, ALPFD activity,
      and FBSR. Ca10(PO4)5(SiO4)(OH) was part of the inorganic component of the bone of
      the SMV-exposed rats.

PMID- 25371213
TI  - The role of autophagy during group B Streptococcus infection of blood-brain
      barrier endothelium.
AB  - Bacterial meningitis occurs when bloodborne pathogens invade and penetrate the
      blood-brain barrier (BBB), provoking inflammation and disease. Group B
      Streptococcus (GBS), the leading cause of neonatal meningitis, can enter human
      brain microvascular endothelial cells (hBMECs), but the host response to
      intracellular GBS has not been characterized. Here we sought to determine whether
      antibacterial autophagy, which involves selective recognition of intracellular
      organisms and their targeting to autophagosomes for degradation, is activated in
      BBB endothelium during bacterial infection. GBS infection resulted in increased
      punctate distribution of GFP-microtubule-associated protein 1 light chain 3 (LC3)
      and increased levels of endogenous LC3-II and p62 turnover, two hallmark
      indicators of active autophagic flux. Infection with GBS mutants revealed that
      bacterial invasion and the GBS pore-forming beta-hemolysin/cytolysin (beta-h/c)
      trigger autophagic activation. Cell-free bacterial extracts containing beta-h/c
      activity induced LC3-II conversion, identifying this toxin as a principal
      provocative factor for autophagy activation. These results were confirmed in vivo
      using a mouse model of GBS meningitis as infection with WT GBS induced autophagy
      in brain tissue more frequently than a beta-h/c-deficient mutant. Elimination of
      autophagy using Atg5-deficient fibroblasts or siRNA-mediated impairment of
      autophagy in hBMECs led to increased recovery of intracellular GBS. However,
      electron microscopy revealed that GBS was rarely found within double membrane
      autophagic structures even though we observed GBS-LC3 co-localization. These
      results suggest that although autophagy may act as a BBB cellular defense
      mechanism in response to invading and toxin-producing bacteria, GBS may actively
      thwart the autophagic pathway. 

PMID- 25371216
TI  - Nemo-like kinase expression predicts poor survival in colorectal cancer.
AB  - Nemo-like kinase (NLK), a serine/threonine protein kinase, was previously
      reported to be associated with tumor proliferation and invasion. The present
      study aimed to evaluate whether NLK participates in the tumorigenesis and
      progression of colorectal cancer (CRC). NLK expression was examined using reverse
      transcription quantitative polymerase chain reaction (RT-qPCR) and western blot
      analysis in 50 paired CRC tissues as well as immunohistochemical analysis of 406
      cases of primary CRC tissues and paired non-cancerous tissues. Correlations
      between NLK expression, the clinicopathological features of CRC patients and
      clinical outcome were then analyzed. NLK expression was found to be significantly
      higher in CRC tissues as well as associated with the depth of tumor invasion,
      lymph node metastasis, distant metastasis, histological differentiation, vascular
      invasion and advanced tumor stage. Patients with NLK-positive tumors demonstrated
      higher rates of recurrence and mortality than patients with NLK-negative tumors.
      Multivariate analyses revealed that NLK expression was an independent factor for
      overall survival [hazard ratio (HR)=0.035; 95% confidence interval (CI)=0.02
      0.19; P<0.001] and disease-free survival (HR=0.033; 95% CI=0.007-0.09; P<0.001)
      in CRC patients. In conclusion, the results of the present study indicated that
      NLK may serve as a novel biomarker for tumor recurrence and survival for CRC
      patients.

PMID- 25371217
TI  - The private health insurance choices of medicare beneficiaries: how much does
      price matter?
AB  - This article presents, critiques, and analyzes the influence of prices on
      insurance choices made by Medicare beneficiaries in the Medicare Advantage, Part
      D, and Medigap markets. We define price as health insurance premiums for the
      Medicare Advantage and Medigap markets, and total out-of-pocket costs (including
      premiums and cost sharing) for the Part D market. In Medicare Advantage and Part
      D, prices only partly explain insurance choices. Enrollment decisions also may be
      influenced by other factors such as the perceived quality of the higher-premium
      plans, better provider networks, lower cost-sharing for services, more generous
      benefits, and a preference for certain brand-name products. In contrast, the one
      study available on the Medigap market concludes that price appears to be
      associated with plan selection. This may be because Medigap benefits are fully
      standardized, making it easier for beneficiaries to compare alternative policies.
      The article concludes by discussing policy options available to Medicare. 

PMID- 25371219
TI  - Climate change: primary care in Bristol is taking the lead in going green.

PMID- 25371220
TI  - Many drugs used for rheumatic disease cause neutropenia.

PMID- 25371218
TI  - Bidirectional links between HIV and intimate partner violence in pregnancy:
      implications for prevention of mother-to-child transmission.
AB  - INTRODUCTION: Prevention of mother-to-child transmission (PMTCT) has the
      potential to eliminate new HIV infections among infants. Yet in many parts of sub
      Saharan Africa, PMTCT coverage remains low, leading to unacceptably high rates of
      morbidity among mothers and new infections among infants. Intimate partner
      violence (IPV) may be a structural driver of poor PMTCT uptake, but has received
      little attention in the literature to date. METHODS: We conducted qualitative
      research in three Johannesburg antenatal clinics to understand the links between
      IPV and HIV-related health of pregnant women. We held focus group discussions
      with pregnant women (n=13) alongside qualitative interviews with health care
      providers (n=10), district health managers (n=10) and pregnant abused women
      (n=5). Data were analysed in Nvivo10 using a team-based approach to thematic
      coding. FINDINGS: We found qualitative evidence of strong bidirectional links
      between IPV and HIV among pregnant women. HIV diagnosis during pregnancy, and
      subsequent partner disclosure, were noted as a common trigger of IPV. Disclosure
      leads to violence because it causes relationship conflict, usually related to
      perceived infidelity and the notion that women are "bringing" the disease into
      the relationship. IPV worsened HIV-related health through poor PMTCT adherence,
      since taking medication or accessing health services might unintentionally alert
      male partners of the women's HIV status. IPV also impacted on HIV-related health
      via mental health, as women described feeling depressed and anxious due to the
      violence. IPV led to secondary HIV risk as women experienced forced sex, often
      with little power to negotiate condom use. Pregnant women described staying
      silent about condom negotiation in order to stay physically safe during
      pregnancy. CONCLUSIONS: IPV is a crucial issue in the lives of pregnant women and
      has bidirectional links with HIV-related health. IPV may worsen access to PMTCT
      and secondary prevention behaviours, thereby posing a risk of secondary
      transmission. IPV should be urgently addressed in antenatal care settings to
      improve uptake of PMTCT and ensure that goals of maternal and child health are
      met in sub-Saharan African settings.

PMID- 25371221
TI  - Airport screening for Ebola: current thermal scanning procedures are unreliable.

PMID- 25371222
TI  - The NHS in Clacton and the 2014 by-election.

PMID- 25371223
TI  - No evidence of industry sponsorship bias in statin trials.

PMID- 25371224
TI  - Advantages of airport screening for Ebola.

PMID- 25371225
TI  - New evidence about the benefits of PCI with regard to mortality.

PMID- 25371226
TI  - Author's reply to Farebrother.

PMID- 25371227
TI  - Investigator contact details should continue to be available after completion of
      clinical trials.

PMID- 25371228
TI  - Authors' reply to O'Neill and colleagues.

PMID- 25371229
TI  - Morphological adaptation and protein modulation of myotendinous junction
      following moderate aerobic training.
AB  - Myotendinous junction is the muscle-tendon interface through which the
      contractile force can be transferred from myofibrils to the tendon extracellular
      matrix. At the ultrastructural level, aerobic training can modify the distal
      myotendinous junction of rat gastrocnemius, increasing the contact area between
      tissues. The aim of this work is to investigate the correlation between
      morphological changes and protein modulation of the myotendinous junction
      following moderate training. For this reason, talin, vinculin and type IV
      collagen amount and spatial distribution were investigated by
      immunohistochemistry and confocal microscopy. The images were then digitally
      analyzed by evaluating fluorescence intensity. Morphometric analysis revealed a
      significant increased thickening of muscle basal lamina in the trained group
      (53.1 +/- 0.4 nm) with respect to the control group (43.9 +/- 0.3 nm), and
      morphological observation showed the presence of an electron-dense area in the
      exercised muscles, close to the myotendinous junction. Protein concentrations
      appeared significantly increased in the trained group (talin +22.2%; vinculin
      +22.8% and type IV collagen +11.8%) with respect to the control group. Therefore,
      our findings suggest that moderate aerobic training induces/causes morphological
      changes at the myotendinous junction, correlated to the synthesis of structural
      proteins of the muscular basal lamina and of the cytoskeleton.

PMID- 25371230
TI  - Incorporation of calcium salts into xanthan gum matrices: hydration, erosion and
      drug release characteristics.
AB  - Xanthan gum (XG), a hydrophilic biopolymer with modified release properties, was
      used to produce directly compressed matrix tablets containing a model drug,
      sodium p-aminosalicylate. Three formulations were prepared, each containing a
      different calcium dihydrate salt: calcium chloride, calcium sulfate or dibasic
      calcium phosphate. The aim of the investigation was to relate the calcium ion
      content and solubility of the calcium salt to the in vitro drug release profile
      of the xanthan matrices. Tablet hydration, erosion and drug release were
      determined in distilled water using the British Pharmacopoeia (BP) paddle method.
      The data showed that the overall drug release was the greatest with addition of
      calcium sulfate, followed by calcium chloride and dibasic calcium phosphate. The
      chloride salt formulation displayed the greatest percentage erosion due to rapid
      mass loss during the initial phase, followed by those with sulfate or phosphate
      salts. As xanthan gel viscosity increased and drug release was also found to be
      lower, it can be concluded that drug release is influenced by the solubility of
      the salt present in the formulation, since these parameters determine the
      viscosity and structure of the gel layer. 

PMID- 25371232
TI  - Reply: To PMID 24974958.

PMID- 25371231
TI  - Is vitamin D insufficiency or deficiency related to the development of
      osteochondritis dissecans?
AB  - PURPOSE: The aetiology of osteochondritis dissecans is still unclear. The aim of
      this prospective pilot study was to analyse whether vitamin D insufficiency, or
      deficiency, might be a contributing etiological factor in the development of an
      OCD lesion. METHODS: The serum level of vitamin D3 in 23 consecutive patients (12
      male and 11 female) suffering from a stage III, or stages III and IV, OCD lesion
      (mostly stage III) admitted for surgery was measured. RESULTS: The patients' mean
      age was 31.3 years and most of them already exhibited closed epiphyseal plates.
      In the majority of patients (18/23), a distinct vitamin D3 deficiency was found,
      two patients were vitamin D3-insufficient and, in three patients, the vitamin D3
      level reached the lowest normal value. CONCLUSION: These first data show that a
      vitamin D3 deficiency rather than an insufficiency may be involved in the
      development of OCD lesions. Probably, with a vitamin D3 substitution, the
      development of an advanced OCD stage could be avoided. Further analyses,
      including morphological analyses regarding a possible osteomalacia, and
      examination of the PTH and other determinants of the bone metabolism, should be
      undertaken to either confirm or refute these data. LEVEL OF EVIDENCE: IV.

PMID- 25371233
TI  - A novel pathogenic mutation of the CYP27B1 gene in a patient with vitamin D
      dependent rickets type 1: a case report.
AB  - BACKGROUND: Rickets can occur due to Vitamin D deficiency or defects in its
      metabolism. Three rare genetic types of rickets with different alterations of
      genes have been reported, including: Vitamin D dependent rickets type 1, Vitamin
      D dependent rickets type 2 or also known as Vitamin D resistant rickets and 25
      hydroxylase deficiency rickets. Vitamin D dependent rickets type 1 is inherited
      in an autosomal recessive pattern, and is caused by mutations in the CYP27B1 gene
      encoding the 1alpha-hydroxylase enzyme. We report here a new mutation in CYP27B1,
      which lead to Vitamin D dependent rickets type 1. CASE PRESENTATION: We report on
      a 13-month-old Arabic Saudi girl with Vitamin D dependent rickets type 1
      presented with multiple fractures and classic features of rickets. A whole exome
      sequencing identified a novel pathogenic missense mutation (CYP27B1:Homozygous
      c.1510C > T(p.Q504X)) which results in a protein truncating alteration. Both
      parents are heterozygous carriers of the mutation. Based on data search in Human
      Gene Mutation Database, 63 CYP27B1 alterations were reported: only 28.6% are
      protein truncating (5 nonsense, 13 frameshift insertions/deletions, 0 gross
      deletions), while 61.9% are non-truncating (38 missense, 1 small in-frame
      insertions/deletion), and 9.5% are possible protein-truncating (5 splice, 1
      regulatory). CONCLUSION: The deleterious effect of this alteration, which was the
      only mutation detected in the CYP27B1 common gene of Vitamin D dependent rickets
      type 1 in the proband, and its autosomal recessive inheritance fashion, both
      support a pathogenic nature of this mutation as the cause of Vitamin D dependent
      rickets type 1.

PMID- 25371234
TI  - Lack of evidence for genomic instability in autistic children as measured by the
      cytokinesis-block micronucleus cytome assay.
AB  - Autism spectrum disorders are a set of neurodevelopmental disorders that are
      highly hereditable. Increased genomic instability has been observed in other
      heritable paediatric neurobiological disorders; therefore, the aim of our study
      was to test the hypothesis that DNA damage is increased in children with autism
      and that B vitamin status may explain variations in genome integrity between
      autistic and normal children. We compared 35 children with autism, 27 of their
      siblings without autism and 25 age- and gender-matched community controls for
      genomic stability using the cytokinesis-block micronucleus cytome (CBMN-cyt)
      assay, B vitamins and homocysteine, as well as autism-related behaviours. It was
      found that there were no differences in CBMN-cyt biomarkers between the three
      groups. Vitamin B2 was significantly raised in children with autism and their
      siblings compared with controls (P = 0.027 and P = 0.016 respectively) but there
      was no difference in other B vitamins or homocysteine. In conclusion, although
      replication using a larger cohort is needed, it appears unlikely that genomic
      instability is a feature of the aetiology of autism. We cannot rule out in utero
      effects or other types of DNA damage not measured by the CBMN-cyt assay.

PMID- 25371235
TI  - TGF-beta regulates the proliferation of lung adenocarcinoma cells by inhibiting
      PIK3R3 expression.
AB  - PIK3R3, an isoform of class IA phosphoinositide 3-kinase (PI3K), specifically
      interacts with cell proliferation regulators, such as retinoblastoma and
      proliferation cell nuclear antigen, to promote cell proliferation. However, the
      mechanisms behind the upstream signaling pathway of PIK3R3 remain unclear to
      date. This study showed that PIK3R3 expression was regulated by transforming
      growth factor-beta (TGF-beta) signaling and that PIK3R3 mediated the TGF-beta
      induced inhibition of lung adenocarcinoma cell proliferation. TGF-beta down
      regulated PIK3R3 expression in lung adenocarcinoma cells. However, this TGF-beta
      induced inhibition of cell proliferation can be attenuated by PIK3R3
      overexpression. In addition, TGF-beta can attenuate the transcriptional activity
      of NKX2.1, a transcription factor that binds to the promoter of PIK3R3. This
      result indicated that TGF-beta regulated PIK3R3 expression by targeting NKX2.1.
      We confirmed the correlation between NKX2.1 and PIK3R3 in clinical samples.
      Therefore, the TGF-beta/NKX2.1/PIK3R3 axis is crucial in the TGF-beta-induced
      inhibition of cell proliferation, and the NKX2.1/PIK3R3 axis might become a
      target in TGF-beta receptor-repressed lung adenocarcinoma.

PMID- 25371236
TI  - Systematic review of outcomes from home-based primary care programs for homebound
      older adults.
AB  - OBJECTIVES: To describe the effect of home-based primary care for homebound older
      adults on individual, caregiver, and systems outcomes. DESIGN: A systematic
      review of home-based primary care interventions for community-dwelling older
      adults (aged >=65) using the Cochrane, PubMed, and MEDLINE databases from the
      earliest available date through March 15, 2014. Studies were included if the
      house calls visitor was the ongoing primary care provider and if the intervention
      measured emergency department visits, hospitalizations, hospital beds days of
      care, long-term care admissions, or long-term care bed days of care. SETTING:
      Home-based primary care programs. PARTICIPANTS: Homebound community-dwelling
      older adults (N = 46,154). MEASUREMENTS: Emergency department visits,
      hospitalizations, hospital bed days of care, long-term care admissions, long-term
      care bed days of care, costs, program design, and individual and caregiver
      quality of life and satisfaction with care. RESULTS: Of 357 abstracts identified,
      nine met criteria for review. The nine interventions were all based in North
      America, with five emerging from the Veterans Affairs system. Eight of nine
      programs demonstrated substantial effects on at least one inclusion outcome, with
      seven programs affecting two outcomes. Six interventions shared three core
      program components: interprofessional care teams, regular interprofessional care
      meetings, and after-hours support. CONCLUSION: Specifically designed home-based
      primary care programs may substantially affect individual, caregiver and systems
      outcomes. Adherence to the core program components identified in this review
      could guide the development and spread of these programs.

PMID- 25371238
TI  - Anatomy and efficiency of urban multimodal mobility.
AB  - The growth of transportation networks and their increasing interconnections,
      although positive, has the downside effect of an increasing complexity which make
      them difficult to use, to assess, and limits their efficiency. On average in the
      UK, 23% of travel time is lost in connections for trips with more than one mode,
      and the lack of synchronization decreases very slowly with population size. This
      lack of synchronization between modes induces differences between the theoretical
      quickest trip and the 'time-respecting' path, which takes into account waiting
      times at interconnection nodes. We analyse here the statistics of these paths on
      the multilayer, temporal network of the entire, multimodal british public
      transportation system. We propose a statistical decomposition - the 'anatomy' -
      of trips in urban areas, in terms of riding, waiting and walking times, and which
      shows how the temporal structure of trips varies with distance and allows us to
      compare different cities. Weaknesses in systems can be either insufficient
      transportation speed or service frequency, but the key parameter controlling
      their global efficiency is the total number of stop events per hour for all
      modes. This analysis suggests the need for better optimization strategies,
      adapted to short, long unimodal or multimodal trips. 

PMID- 25371237
TI  - Chemoproteomics reveals Toll-like receptor fatty acylation.
AB  - BACKGROUND: Palmitoylation is a 16-carbon lipid post-translational modification
      that increases protein hydrophobicity. This form of protein fatty acylation is
      emerging as a critical regulatory modification for multiple aspects of cellular
      interactions and signaling. Despite recent advances in the development of
      chemical tools for the rapid identification and visualization of palmitoylated
      proteins, the palmitoyl proteome has not been fully defined. Here we sought to
      identify and compare the palmitoylated proteins in murine fibroblasts and
      dendritic cells. RESULTS: A total of 563 putative palmitoylation substrates were
      identified, more than 200 of which have not been previously suggested to be
      palmitoylated in past proteomic studies. Here we validate the palmitoylation of
      several new proteins including Toll-like receptors (TLRs) 2, 5 and 10, CD80,
      CD86, and NEDD4. Palmitoylation of TLR2, which was uniquely identified in
      dendritic cells, was mapped to a transmembrane domain-proximal cysteine.
      Inhibition of TLR2 S-palmitoylation pharmacologically or by cysteine mutagenesis
      led to decreased cell surface expression and a decreased inflammatory response to
      microbial ligands. CONCLUSIONS: This work identifies many fatty acylated proteins
      involved in fundamental cellular processes as well as cell type-specific
      functions, highlighting the value of examining the palmitoyl proteomes of
      multiple cell types. S-palmitoylation of TLR2 is a previously unknown
      immunoregulatory mechanism that represents an entirely novel avenue for
      modulation of TLR2 inflammatory activity.

PMID- 25371239
TI  - Generation of ultra-short hydrogen atom pulses by bunch-compression photolysis.
AB  - Ultra-short light pulses enable many time-resolved studies in chemistry,
      especially when used in pump-probe experiments. However, most chemical events are
      not initiated by light, but rather by collisions. Time-resolved collisional
      experiments require ultra-short pulses of atoms and molecules--sadly, methods for
      producing such pulses are so far unknown. Here we introduce bunch-compression
      photolysis, an approach to forming ultra-short and highly intense pulses of
      neutral atoms. We demonstrate H-atom pulses of 1.2+/-0.3 ns duration, far shorter
      than any previously reported. Owing to its extraordinarily simple physical
      principles, we can accurately model the method--the model shows H-atom pulses as
      short as 110-ps are achievable. Importantly, due to the bunch-compression, large
      (mm(3)) photolysis volumes are possible, a key advantage for pulse intensity.
      This technique overcomes the most challenging barrier to a new class of
      experiments on time-resolved collisions involving atoms and molecules.

PMID- 25371240
TI  - A comparative study of an NGO-sponsored CHW programme versus a ministry of health
      sponsored CHW programme in rural Kenya: a process evaluation.
AB  - The varied performance of Community Health Worker (CHW) programmes in different
      contexts has highlighted the need for implementation of research that focuses on
      programme delivery issues. This paper presents the results of process evaluations
      conducted on two different models of CHW programme delivery in adjacent rural
      communities in in Gem District of Western Kenya. One model was implemented by the
      Millennium Villages Project (MVP), and the other model was implemented in
      partnership with the Ministry of Health (MoH) as part of Kenya's National CHW
      programme. 

PMID- 25371241
TI  - Hutchinson-Gilford progeria syndrome with scleroderma-like skin changes due to a
      homozygous missense LMNA mutation.

PMID- 25371242
TI  - Is testosterone deficiency a possible risk factor for priapism associated with
      sickle-cell disease?
AB  - PURPOSE: The purpose of this study was to determine the association of
      testosterone deficiency and priapism in adult men with sickle cell disease (SCD).
      METHODS: A cross-sectional study of 50 adult men with SCD (hemoglobin SS) was
      performed. All patients had early morning blood taken for total and free
      testosterone, FSH, LH, prolactin, lipid levels, LDH and hematological indices.
      Patients completed an interviewer-administered questionnaire regarding priapism
      frequency, duration and treatment. Testosterone deficiency was defined as a serum
      total testosterone<12 nmol/L (346 ng/dL). RESULTS: The mean age of the study
      population was 34.2+/-8.9 years. Priapism was noted in 24 (48%) patients and was
      most frequently seen in men between ages 18-25 years. Testosterone deficiency was
      observed in 11 of the 50 (22%) patients, particularly in 6 of 24 (25%) patients
      with histories of priapism. There was no difference in mean total testosterone
      levels in patients with and without a history of priapism (16.7+/-4.9 nmol/L and
      15.4+/-5.9 nmol/L, respectively) (p=0.43). Similarly, there was no difference in
      serum LH and FSH levels based on history of priapism. CONCLUSION: Testosterone
      deficiency is prevalent in patients with SCD; however, we did not identify an
      association based on a history of priapism. Larger, prospectively gathered data
      are needed to define the priapism profile of SCD patients with testosterone
      deficiency.

PMID- 25371243
TI  - Potential role of the donor in hepatocellular carcinoma recurrence after liver
      transplantation.
AB  - A subset of liver transplantation (LT) recipients who undergo transplantation for
      hepatocellular carcinoma (HCC) will develop postoperative recurrence. There has
      yet to be a thorough investigation of donor factors influencing recurrence. Data
      regarding adult, primary LT recipients with HCC (n = 5002) who underwent
      transplantation between January 1, 2006 and September 30, 2010 were extracted
      from the United Network for Organ Sharing database, and the cumulative incidence
      of post-LT recurrence by donor factors was subsequently estimated. Among the HCC
      LT recipients, 324 (6.5%) developed recurrence. An analysis of donor
      characteristics demonstrated a higher cumulative incidence of recurrence within 4
      years of transplantation among recipients with donors >= 60 years old (11.8%
      versus 7.3% with donors < 60 years old, P < 0.001) and with donors from a
      nonlocal share distribution (10.6% versus 7.4% with donors with a local share
      distribution, P = 0.004). The latter 2 findings held true in a multivariate
      analysis: the risk of HCC recurrence increased by 70% for recipients of livers
      from donors >= 60 years old [subhazard ratio (SHR) = 1.70, 95% confidence
      interval (CI) = 1.31-2.20, P < 0.001] and by 42% for recipients of nonlocal share
      distribution livers (SHR = 1.42, 95% CI = 1.09-1.84, P = 0.009) after adjustments
      for clinical characteristics. In conclusion, the consideration of certain donor
      factors may reduce the cumulative incidence of posttransplant HCC recurrence and
      thus improve long-term survival after LT.

PMID- 25371246
TI  - Quantification of nerve agent biomarkers in human serum and urine.
AB  - A novel method for rapid and sensitive quantification of the nerve agent
      metabolites ethyl, isopropyl, isobutyl, cyclohexyl, and pinacolyl
      methylphosphonic acid has been established by combining salting-out assisted
      liquid-liquid extraction (SALLE) and online solid phase extraction-liquid
      chromatography-tandem mass spectrometry (SPE-LC-MS/MS). The procedure allows
      confirmation of nerve agent exposure within 30 min from receiving a sample, with
      very low detection limits for the biomarkers of 0.04-0.12 ng/mL. Sample
      preparation by SALLE was performed in less than 10 min, with a common procedure
      for both serum and urine. Analyte recoveries of 70-100% were obtained using
      tetrahydrofuran as extraction solvent and Na2SO4 to achieve phase separation.
      After SALLE, selective analyte retention was obtained on a ZrO2 column by Lewis
      acid-base and hydrophilic interactions with acetonitrile/1% CH3COOH (82/18) as
      the loading mobile phase. The phosphonic acids were backflush-desorbed onto a
      polymeric zwitterionic column at pH 9.8 and separated by hydrophilic interaction
      liquid chromatography. The method was linear (R(2) >= 0.995) from the limits of
      quantification to 50 ng/mL, and the within- and between-assay repeatability at 20
      ng/mL were below 5% and 10% relative standard deviation, respectively. 

PMID- 25371245
TI  - Effectiveness of HCV core antigen and RNA quantification in HCV-infected and
      HCV/HIV-1-coinfected patients.
AB  - BACKGROUND: The measurement of hepatitis C virus core antigen (HCV-coreAg) has
      been shown to be an indicator of active HCV infection. The aim of the present
      study was 1) to investigate the stability and effectiveness of HCV-coreAg and HCV
      RNA quantification in HCV infection with or without HIV-1 coinfection, 2) to
      explore the association between the HCV-coreAg/HCV-RNA (Ag/RNA) ratio and the
      immune status in chronic HCV/HIV-1-coinfected patients. METHODS: A longitudinal
      investigation comprised of 227 HCV-monoinfected (n = 129) and HCV/HIV-1
      coinfected (n = 98) patients was initiated in August 2009, and 139 (73 with HCV
      monoinfection and 66 with HCV/HIV-1 coinfection) were followed up in August 2012.
      Both HCV core antigen and HCV RNA quantification were determined on this
      cryopreserved plasma. HCV core antigen and HCV RNA quantification were performed
      subsequently. In addition, an in vitro experiment investigating the possibility
      of degradation of HCV components (core antigen and RNA) were conducted. RESULTS:
      Significant and stable correlations (p < 0.001) were observed both in chronic HCV
      monoinfected and HCV/HIV-1-coinfected patients over the 3-year observation.
      Coinfected patients with immunocompromised condition had a significantly higher
      (p < 0.05) Ag/RNA ratios than those patients with immunocompetent condition both
      at two time points (2009 and 2012). Moreover, the Ag/RNA ratios were negatively
      correlated with CD4+ T-cell counts (p < 0.001). An in vitro experiment
      investigated the possibility of the slower degradation of HCV particles under HIV
      related immunocompromised condition was conducted and the data demonstrated that
      the Ag/RNA ratios were significantly higher in HIV-1-positive plasma than in
      healthy plasma (p = 0.005) in this study. CONCLUSIONS: Our longitudinal study
      indicated that the HCV-coreAg presented comparable dynamics over time as HCV RNA
      in chronic HCV-infected patients. Meanwhile, the HCV-coreAg/HCV-RNA ratio was
      closely associated with immune status in HCV/HIV-1-coinfected patients.

PMID- 25371244
TI  - TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats.
AB  - Orofacial cold hyperalgesia is known to cause severe persistent pain in the face
      following trigeminal nerve injury or inflammation, and transient receptor
      potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be
      involved in cold hyperalgesia. However, how these two receptors are involved in
      cold hyperalgesia is not fully understood. To clarify the mechanisms underlying
      facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the
      expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG
      neuronal excitability to cold stimulation following facial capsaicin injection
      were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold
      stimulation of the lateral facial skin was significantly decreased following
      facial capsaicin injection. This reduction of HWRT was significantly recovered
      following local injection of TRPV1 antagonist as well as TRPA1 antagonist.
      Approximately 30% of TG neurons innervating the lateral facial skin expressed
      both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed
      TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly
      increased following facial capsaicin injection and this increase was recovered by
      pretreatment with TRPA1 antagonist. These findings suggest that TRPA1
      sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia
      following facial skin capsaicin injection. 

PMID- 25371247
TI  - The prognostic significance of atrial fibrillation in heart failure with a
      preserved and reduced left ventricular function: insights from a meta-analysis.
AB  - BACKGROUND: The prognostic significance of atrial fibrillation (AF) in patients
      with heart failure remains inconclusive. AIMS: To perform a meta-analysis of the
      published data to study the prognostic significance of AF in heart failure
      patients and to determine whether this relates to the presence of preserved or
      reduced left ventricular systolic function. METHODS AND RESULTS: We searched the
      MEDLINE (from inception to May 2014) supplemented by manual searches of
      references of relevant retrieved articles. Randomized clinic trials and
      observational studies were included with hazard ratios (HRs) of AF for mortality
      in chronic heart failure patients. The search strategy yielded 20 studies that
      met our eligibility criteria. A total of 61 240 AF patients in 152 306 heart
      failure participants were included, with 39 879 deaths occurring during follow
      up. Pooled HRs for AF in mortality in heart failure was 1.17 (95% confidence
      intervals: 1.11-1.23) using random-effect model (I(2)  = 44.5%). There was a
      significant difference of combined HRs between heart failure patients with
      preserved and reduced left ventricular ejection fraction (LVEF) in separate
      analysis. Sensitivity analysis supported the consistence of the results.
      CONCLUSIONS: Atrial fibrillation is significantly associated with increased
      mortality in heart failure patients. The prognostic significance of AF may be
      different between heart failure with preserved and reduced LVEF, and AF is
      associated with poorer prognosis in heart failure patients with preserved LVEF.

PMID- 25371248
TI  - Structural, optical and sensing properties of novel Eu(III) complexes with furan-
      and pyridine-based ligands.
AB  - A new family of imine and amine-based racemic ligands containing furan or
      pyridine as an aromatic donating ring [N,N'-bis(2-pyridylmethylidene)-1,2-(R,R +
      S,S)-cyclohexanediamine, L1; N,N'-bis(2-furanylmethylidene)-1,2-(R,R + S,S)
      cyclohexanediamine, L2; N,N'-bis(2-pyridylmethyl)-1,2-(R,R + S,S)
      cyclohexanediamine, L3; and N,N'-bis(2-furanylmethyl)-1,2-(R,R + S,S)
      cyclohexanediamine, L4] and their trifluoromethanesulphonate (CF3SO3(-), OTf(-))
      and nitrate Eu(III) complexes is studied in acetonitrile (AN) solution. The
      stoichiometry and stabilities of the formed complexes are obtained by means of
      spectrophotometric titrations: when Eu(III) triflate is used as a starting salt,
      two mononuclear species (1:1 and 1:2) are detected, while only the 1:1 complex is
      observed when the nitrate salt is employed. The stability of these complexes, as
      well as the geometry of their Eu(III) environment, is significantly dependent on
      the nature of the ligand employed (imine or amine, furan or pyridine-based). DFT
      calculations show that all donor atoms are coordinated to the metal ion in the
      1:1 EuL(L = L1-L4) species and suggest that the higher stability of the complexes
      with L1 and L2 with respect to L3 and L4 is mostly due to the higher degree of
      preorganization of the former species. The optical response of the imine-based L1
      and L2 Eu complexes, produced by NO3(-) coordination, has been studied in order
      to assess their application as sensing devices. With both ligands, an increase of
      the emission intensity on the addition of the nitrate ion is observed. This is
      higher for the EuL2 complex and underlines the important role of the nature of
      the heteroaromatic ring. Finally, it is worth noting that an efficient energy
      transfer process from the ligand to the metal is present in the case of the 1:1
      triflate Eu(III) complex with the ligand L1.

PMID- 25371249
TI  - The influence of Selank on the parameters of the hemostasis system, lipid
      profile, and blood sugar level in the course of experimental metabolic syndrome.

PMID- 25371250
TI  - The role of incretin as an integrator of sodium and water balance regulation.

PMID- 25371251
TI  - The effect of tactivin on analgesia induced by acute and chronic immobilization.

PMID- 25371252
TI  - Modulating effect of the cardiotonic steroid marinobufagenin on slow sodium
      channels.

PMID- 25371253
TI  - Vegetation and climate reconstruction for the bale mountains (Ethiopia) in the
      Holocene according to the pollen analysis and radiocarbon dating of zoogenic
      deposits.

PMID- 25371254
TI  - Carbon balance in tundra under contemporary climate: significance of belowground
      net carbon flux.

PMID- 25371256
TI  - Seed productivity and imprinting expression in apomictic maize-Tripsacum hybrids.

PMID- 25371255
TI  - Fur structure and grooming in the semi-aquatic mammal Russian desman (Desmana
      moschata L.).

PMID- 25371257
TI  - Local multifractal analysis of the spatial structure of meadow comminities at
      small scale.

PMID- 25371258
TI  - Dynamics of forest vegetation after the reduction of industrial emissions: fast
      recovery or continued degradation?

PMID- 25371259
TI  - Participation of proteinase inhibitors in protection of tomato plants against
      root-knot nematodes.

PMID- 25371260
TI  - Expression of hypoxia-associated genes in multipotent mesenchymal stromal cells
      during long-term cultivation at low oxygen.

PMID- 25371261
TI  - The role of interleukin 7 and its cell receptor in a poor recovery of CD4(+) T
      cells in HIV-infected patients receiving antiretroviral therapy.

PMID- 25371263
TI  - Age-related changes in the myocardium of the Japanese quail (Coturnix japonica)
      as a model of accelerated aging of the heart.

PMID- 25371262
TI  - The role of the Sema4d/CD72-dependent signal in the regulation of B-cell activity
      in multiple sclerosis.

PMID- 25371264
TI  - The importance of nutritional care in HIV-infected children in resource-limited
      settings.
AB  - Renewed efforts to provide proper nutritional care are essential for appropriate
      pediatric HIV management. Current studies support the use of vitamin A and
      macronutrients that increase caloric and protein intake. With additional research
      on key issues such as the needed composition and timing for nutritional
      supplementation, we can determine the best strategies to support the growth and
      development of HIV-infected children in resource-limited settings. Malnutrition
      among children is common in the resource-limited settings where HIV infection is
      most prevalent. While malnutrition is associated with higher morbidity and
      mortality for HIV-infected children, there is only limited evidence to guide the
      use of nutritional support for HIV-infected children. The best studied is vitamin
      A, which is associated with improved mortality and clinical outcomes. Zinc and
      multivitamin supplementation have not consistently been associated with clinical
      benefits. Limited research suggests macronutrient supplementation, which
      typically uses enriched formulas or foods, improves key anthropometrics for HIV
      infected children, but the optimal composition of nutrients for supplementation
      has not been determined. More research is needed to understand the most efficient
      and sustainable ways to ensure adequate nutrition in this vulnerable population. 

PMID- 25371265
TI  - Arsenic sulfide as a potential anti-cancer drug.
AB  - Arsenic sulfide (As4S4) is the main component of realgar, which is widely used in
      traditional Chinese medicine. Previous studies have shown the beneficial effects
      of As4S4 in the treatment of hematological malignant diseases, however, its
      effects on solid tumors have yet to be fully elucidated. The current study aimed
      to explore the anti-cancer effect and the mechanism of As4S4 on solid tumors in
      vitro and in vivo. Cells from four human solid tumor cell lines, including the
      MKN45 gastric cancer cell line, the A375 malignant melanoma cell line, the 8898
      pancreatic carcinoma cell line and the HepG2 hepatocellular carcinoma cell line,
      were treated with As4S4 in vitro, using the L02 embryonic liver cells as a
      control. The efficacy of As4S4 was assessed in vivo using mice implanted with
      Lewis lung carcinoma cells. The results of the current study demonstrated that
      As4S4 significantly inhibited the proliferation of solid tumor cells in a dose-
      and time-dependent manner, but produced a less pronounced effect on L02 cells.
      Additionally, As4S4 was observed to induce apoptosis (including morphological
      changes and an enhanced sub-G1 population), which was accompanied by the
      activation of caspase-3 and -9. Furthermore, treatment with As4S4 significantly
      inhibited the growth of implanted tumors in mice. These results suggest that
      As4S4 possesses potent in vitro and in vivo antitumor activity via the induction
      of cell apoptosis.

PMID- 25371266
TI  - Bioavailability of metal ions and evolutionary adaptation.
AB  - The evolution of life on earth has been a long process that began nearly 3,5 x
      109 years ago. In their initial moments, evolution was mainly influenced by
      anaerobic environments; with the rise of O2 and the corresponding change in
      bioavailability of metal ions, new mechanisms of survival were created. Here we
      review the relationships between ancient atmospheric conditions, metal ion
      bioavailability and adaptation of metals homeostasis during early evolution. A
      general picture linking geochemistry, biochemistry and homeostasis is supported
      by the reviewed literature and is further illustrated in this report using simple
      database searches. 

PMID- 25371268
TI  - The Chemical Origin of Behavior is Rooted in Abiogenesis.
AB  - We describe the initial realization of behavior in the biosphere, which we term
      behavioral chemistry. If molecules are complex enough to attain a stochastic
      element to their structural conformation in such as a way as to radically affect
      their function in a biological (evolvable) setting, then they have the capacity
      to behave. This circumstance is described here as behavioral chemistry, unique in
      its definition from the colloquial chemical behavior.  This transition between
      chemical behavior and behavioral chemistry need be explicit when discussing the
      root cause of behavior, which itself lies squarely at the origins of life and is
      the foundation of choice.  RNA polymers of sufficient length meet the criteria
      for behavioral chemistry and therefore are capable of making a choice. 

PMID- 25371267
TI  - Chromosome Replication in Escherichia coli: Life on the Scales.
AB  - At all levels of Life, systems evolve on the 'scales of equilibria'. At the level
      of bacteria, the individual cell must favor one of two opposing strategies and
      either take risks to grow or avoid risks to survive. It has been proposed in the
      Dualism hypothesis that the growth and survival strategies depend on non
      equilibrium and equilibrium hyperstructures, respectively. It has been further
      proposed that the cell cycle itself is the way cells manage to balance the ratios
      of these types of hyperstructure so as to achieve the compromise solution of
      living on the two scales. Here, we attempt to re-interpret a major event, the
      initiation of chromosome replication in Escherichia coli, in the light of scales
      of equilibria. This entails thinking in terms of hyperstructures as responsible
      for intensity sensing and quantity sensing and how this sensing might help
      explain the role of the DnaA protein in initiation of replication. We outline
      experiments and an automaton approach to the cell cycle that should test and
      refine the scales concept. 

PMID- 25371269
TI  - Life's Order, Complexity, Organization, and Its Thermodynamic-Holistic
      Imperatives.
AB  - In memoriam Jeffrey S. Wicken (1942-2002)-the evolutionarily minded biochemist,
      who in the 1970/80s strived for a synthesis of biological and physical theories
      to fathom the tentative origins of life. Several integrative concepts are worth
      remembering from Wicken's legacy. (i) Connecting life's origins and complex
      organization to a preexisting physical world demands a thermodynamically sound
      transition. (ii) Energetic 'charging' of the prebiosphere must precede the
      emergence of biological organization. (iii) Environmental energy gradients are
      exploited progressively, approaching maximum interactive structure and minimum
      dissipation. (iv) Dynamic self-assembly of prebiotic organic matter is driven by
      hydrophobic tension between water and amphiphilic building blocks, such as
      aggregating peptides from non-polar amino acids and base stacking in nucleic
      acids. (v) The dynamics of autocatalytic self-organization are facilitated by a
      multiplicity of weak interactions, such as hydrogen bonding, within and between
      macromolecular assemblies. (vi) The coevolution of (initially uncoded) proteins
      and nucleic acids in energy-coupled and metabolically active so-called
      'microspheres' is more realistic as a kinetic transition model of primal
      biogenesis than 'hypercycle replication' theories for nucleic acid replicators on
      their own. All these considerations blend well with the current understanding
      that sunlight UV-induced photo-electronic excitation of colloidal metal sulfide
      particles appears most suitable as a prebiotic driver of organic synthesis
      reactions, in tight cooperation with organic, phase-separated, catalytic
      'microspheres'. On the 'continuist vs. miraculist' schism described by Iris Fry
      for origins-of-life considerations (Table 1), Wicken was a fervent early
      protagonist of holistic 'continuist' views and agenda. 

PMID- 25371270
TI  - Molecular mechanisms of survival strategies in extreme conditions.
AB  - Today, one of the major challenges in biophysics is to disclose the molecular
      mechanisms underlying biological processes. In such a frame, the understanding of
      the survival strategies in extreme conditions received a lot of attention both
      from the scientific and applicative points of view. Since nature provides
      precious suggestions to be applied for improving the quality of life,
      extremophiles are considered as useful model-systems. The main goal of this
      review is to present an overview of some systems, with a particular emphasis on
      trehalose playing a key role in several extremophile organisms. The attention is
      focused on the relation among the structural and dynamic properties of
      biomolecules and bioprotective mechanisms, as investigated by complementary
      spectroscopic techniques at low- and high-temperature values. 

PMID- 25371271
TI  - Quantum biological channel modeling and capacity calculation.
AB  - Quantum mechanics has an important role in photosynthesis, magnetoreception, and
      evolution. There were many attempts in an effort to explain the structure of
      genetic code and transfer of information from DNA to protein by using the
      concepts of quantum mechanics. The existing biological quantum channel models are
      not sufficiently general to incorporate all relevant contributions responsible
      for imperfect protein synthesis. Moreover, the problem of determination of
      quantum biological channel capacity is still an open problem. To solve these
      problems, we construct the operator-sum representation of biological channel
      based on codon basekets (basis vectors), and determine the quantum channel model
      suitable for study of the quantum biological channel capacity and beyond. The
      transcription process, DNA point mutations, insertions, deletions, and
      translation are interpreted as the quantum noise processes. The various types of
      quantum errors are classified into several broad categories: (i) storage errors
      that occur in DNA itself as it represents an imperfect storage of genetic
      information, (ii) replication errors introduced during DNA replication process,
      (iii) transcription errors introduced during DNA to mRNA transcription, and (iv)
      translation errors introduced during the translation process. By using this
      model, we determine the biological quantum channel capacity and compare it
      against corresponding classical biological channel capacity. We demonstrate that
      the quantum biological channel capacity is higher than the classical one, for a
      coherent quantum channel model, suggesting that quantum effects have an important
      role in biological systems. The proposed model is of crucial importance towards
      future study of quantum DNA error correction, developing quantum mechanical model
      of aging, developing the quantum mechanical models for tumors/cancer, and study
      of intracellular dynamics in general. 

PMID- 25371272
TI  - An efficient biometric and password-based remote user authentication using smart
      card for Telecare Medical Information Systems in multi-server environment.
AB  - The medical organizations have introduced Telecare Medical Information System
      (TMIS) to provide a reliable facility by which a patient who is unable to go to a
      doctor in critical or urgent period, can communicate to a doctor through a
      medical server via internet from home. An authentication mechanism is needed in
      TMIS to hide the secret information of both parties, namely a server and a
      patient. Recent research includes patient's biometric information as well as
      password to design a remote user authentication scheme that enhances the security
      level. In a single server environment, one server is responsible for providing
      services to all the authorized remote patients. However, the problem arises if a
      patient wishes to access several branch servers, he/she needs to register to the
      branch servers individually. In 2014, Chuang and Chen proposed an remote user
      authentication scheme for multi-server environment. In this paper, we have shown
      that in their scheme, an non-register adversary can successfully logged-in into
      the system as a valid patient. To resist the weaknesses, we have proposed an
      authentication scheme for TMIS in multi-server environment where the patients can
      register to a root telecare server called registration center (RC) in one time to
      get services from all the telecare branch servers through their registered smart
      card. Security analysis and comparison shows that our proposed scheme provides
      better security with low computational and communication cost.

PMID- 25371273
TI  - Clinical outcomes of chronic hepatitis C patients related to baseline liver
      fibrosis stage: a hospital-based linkage study.
AB  - BACKGROUND AND AIMS: Rates of long-term clinical outcomes of chronic hepatitis C
      in patients with none, mild or severe liver fibrosis are required to determine
      benefits of anti-viral therapies. This study evaluated long-term outcomes for
      chronic hepatitis C stratified by all Metavir fibrosis stages. METHODS: Clinical
      outcomes were determined using population-based data linkage methodology for 880
      hepatitis C patients who had a liver biopsy performed from 1992 to 2012. RESULTS:
      During 9386 person-years of follow up, 28 patients developed hepatocellular
      carcinoma, 58 developed liver decompensation and 122 died or underwent liver
      transplantation. There was no significant difference in liver-related death for
      those with F0-F2 with an 18-year survival probability >94%. Hazard ratio of liver
      related death for F3 compared with F0-F2 was 4.24 (P = 0.003), with no
      significant difference in the first 13-year follow up. The 15-year decompensation
      free survival for F0, F1 and F2 was 100%, 96% and 94% respectively and for
      hepatocellular carcinoma-free survival was 100%, 99% and 98%. Hazard ratio of
      liver complication (hepatocellular carcinoma or decompensation)-free survival for
      F3 compared with F0-F2 was 3.22 (P = 0.001), with no significant difference
      during the first 7-year follow up. F4 had significantly higher risk of liver
      related death, decompensation and hepatocellular carcinoma than F3 (P < 0.001).
      CONCLUSIONS: Chronic hepatitis C patients with F2 or less had few liver
      complications after 15 years. For F3 patients, the significant increase in liver
      related death occurred after 13 years and for liver complications after 7 years.

PMID- 25371274
TI  - Facile synthesis of hydrophilic multi-colour and upconversion photoluminescent
      mesoporous carbon nanoparticles for bioapplications.
AB  - Hydrophilic mesoporous carbon nanoparticles (MCNs) have been synthesized via an
      extremely facile precursor carbonization-in-hot solvent route. The synthesized
      MCNs show well-defined particle and pore size distribution at around 100 nm and
      2.7 nm, respectively, and multicolor and upconversion photoluminescence, which
      endow the MCNs with multicolor/upconversion bioimaging and drug delivery
      properties. 

PMID- 25371275
TI  - Comparison of NSAID patch given as monotherapy and NSAID patch in combination
      with transcutaneous electric nerve stimulation, a heating pad, or topical
      capsaicin in the treatment of patients with myofascial pain syndrome of the upper
      trapezius: a pilot study.
AB  - OBJECTIVE: This study compared the therapeutic effect of monotherapy with a
      nonsteroidal anti-inflammatory drug (NSAID) patch vs an NSAID patch combined with
      transcutaneous electric nerve stimulation (TENS), a heating pad, or topical
      capsaicin in the treatment of patients with myofascial pain syndrome (MPS) of the
      upper trapezius. DESIGN: A randomized, single-blind, controlled study of
      combination therapy for patients with MPS was performed. METHODS: Ninety-nine
      patients were randomly assigned to one of four different self-management methods
      for treatment: NSAID patch (N = 25), NSAID patch + TENS (N = 24), NSAID patch +
      heating pad (N = 25), and NSAID patch + topical capsaicin (N = 25). The NSAID
      patch used in this study was a ketoprofen patch. All treatment groups were
      observed for 2 weeks, and the numeric rating scale (NRS) pain score, cervical
      active range of motion, pressure pain threshold, and Neck Disability Index were
      assessed. RESULTS: There was no significant difference between the NSAID patch
      alone group and the three combination therapy groups with respect to decrease in
      NRS score from baseline (day 0) to each period of observation. In covariate
      analysis, although there was no difference among the groups in most of the
      periods, the data at day 14 indicated a trend (P = 0.057). There were no
      significant differences in the other variables. CONCLUSIONS: We did not observe a
      statistical difference in improvements to the clinical variables among the four
      different methods. However, further studies regarding the effectiveness of a
      mixture of topical capsaicin and ketoprofen in patients with MPS should be
      considered.

PMID- 25371276
TI  - Angiosarcoma Developing in a Vagal Schwannoma: A Rare Case Report.
AB  - Angiosarcoma arising in a schwannoma is extremely rare with only fourteen cases
      having been reported in the literature to the best of our knowledge. Amongst
      these fourteen, only five cases developed from vagal schwannoma. We describe a
      case of epithelioid angiosarcoma arising in a long standing vagal schwannoma in a
      41 years male patient. Grossly the tumor was well encapsulated with variegated
      cut surface. On microscopy the tumor had two distinct components composed of
      benign schwannoma and malignant angiosarcoma which were further confirmed by
      immunohistochemistry. On further work up, he was found to have multiple distant
      metastases. This is the sixth reported case of angiosarcoma arising in a vagal
      schwannoma. The proposed histogenesis of this rare transformation, its prognostic
      factors and a review of literature regarding this entity is discussed.

PMID- 25371277
TI  - Domesticating the Drone: The Demilitarisation of Unmanned Aircraft for Civil
      Markets.
AB  - Remotely piloted aviation systems (RPAS) or 'drones' are well known for their
      military applications, but could also be used for a range of non-military
      applications for state, industrial, commercial and recreational purposes. The
      technology is advanced and regulatory changes are underway which will allow their
      use in domestic airspace. As well as the functional and economic benefits of a
      strong civil RPAS sector, the potential benefits for the military RPAS sector are
      also widely recognised. Several actors have nurtured this dual-use aspect of
      civil RPAS development. However, concerns have been raised about the public
      rejecting the technology because of their association with military applications
      and potentially controversial applications, for example in policing and border
      control. In contrast with the enthusiasm for dual-use exhibited throughout the EC
      consultation process, the strategy for avoiding public rejection devised in its
      roadmap would downplay the connection between military and non-military RPAS and
      focus upon less controversial applications such as search and rescue. We reflect
      upon this contrast in the context of the European agenda of responsible research
      and innovation. In doing so, we do not rely upon critique of drones per se, in
      their neither their civil nor military guise, but explore the extent to which
      current strategies for managing their public acceptability are compatible with a
      responsible and socially beneficial development of RPAS for civil purposes. 

PMID- 25371278
TI  - Sphingosine 1-phosphate has anti-apoptotic effect on liver sinusoidal endothelial
      cells and proliferative effect on hepatocytes in a paracrine manner in human.
AB  - AIM: Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite
      released from erythrocytes and platelets, and is a potent stimulus for
      endothelial cell proliferation. However, the role of S1P on human liver
      sinusoidal endothelial cells (LSEC) remains unclear. The proliferation and
      inhibition of apoptosis in LSEC are involved in the promotion of liver
      regeneration and the suppression of liver injury after liver resection and
      transplantation. The aim of this study is to investigate the role of S1P on human
      LSEC and the interaction between S1P and LSEC in hepatocyte proliferation in
      vitro. METHODS: Immortalized human LSEC were used. LSEC were cultured with S1P,
      and the cell proliferation, anti-apoptosis, signal transductions and production
      of cytokines and growth factors were subsequently examined. To investigate the
      interaction between S1P and LSEC in hepatocyte proliferation, primary human
      hepatocytes were cultured with the supernatants of LSEC with and without S1P. DNA
      synthesis and signal transductions in hepatocytes were examined. RESULTS: S1P
      induced LSEC proliferation through activation of Akt and extracellular signal
      related kinase pathways and suppressed LSEC apoptosis by affecting the expression
      levels of Bcl-2, Bax and cleaved caspase-3. S1P promoted interleukin-6 (IL-6) and
      vascular endothelial growth factor (VEGF) production in LSEC. The supernatants of
      LSEC cultured with S1P enhanced hepatocyte DNA synthesis more strongly than the
      supernatants of LSEC cultured without S1P through activation of the signal
      transducer and activator of transcription-3 pathway. CONCLUSION: S1P has
      proliferative and anti-apoptotic effects and promotes the production of IL-6 and
      VEGF in human LSEC, thereby promoting hepatocyte proliferation.

PMID- 25371279
TI  - Shank-rearfoot joint coupling in young adults with chronic ankle instability: a
      cross-correlation analysis.
AB  - AIM: Chronic ankle instability (CAI) has been associated with changes in gait
      kinematics which may be associated with the continued instability in this
      population. Abnormalities in shank-rearfoot joint coupling during gait may be
      associated with CAI. Cross-correlation analysis provides an estimate of both
      synchronous and asynchronous coherency between shank and rearfoot motion during
      gait. The aim of this study was to identify the coupling relationship between
      transverse plane shank and frontal plane rearfoot motion throughout the entire
      gait cycle using cross-correlation analysis. METHODS: Twenty-eight active adults
      (CAI, N.=15, control, N.=13) participated. Using a 12-camera motion analysis
      system and an instrumented treadmill, shank rotation and rearfoot
      inversion/eversion kinematics were collected during walking and jogging. Cross
      correlation coefficients with lag times ranging from +15% to -15% were generated
      from subject means across three strides and compared between the healthy and CAI
      groups at each speed. RESULTS: During walking, the CAI group demonstrated
      stronger cross-correlation coefficients than the control group from lag +10 to
      +15 (P<0.05). Likewise, during jogging, the CAI group exhibited stronger cross
      correlation coefficients than the control group at lags +6 to +15 (P<0.05).
      CONCLUSION: The CAI group demonstrated stronger asynchronous coupling
      relationships between shank rotation and rearfoot inversion-eversion than the
      control group during both walking and jogging. The more pronounced coupling
      behavior in the CAI group may indicate less functional variability in shank and
      rearfoot kinematics during gait due to a more constrained and less adaptable
      sensorimotor system.

PMID- 25371280
TI  - Protein enrichment of an Opuntia ficus-indica cladode hydrolysate by cultivation
      of Candida utilis and Kluyveromyces marxianus.
AB  - BACKGROUND: The cladodes of Opuntia ficus-indica (prickly pear cactus) have a low
      protein content; for use as a balanced feed, supplementation with other protein
      sources is therefore desirable. We investigated protein enrichment by cultivation
      of the yeasts Candida utilis and Kluyveromyces marxianus in an enzymatic
      hydrolysate of the cladode biomass. RESULTS: Dilute acid pretreatment and
      enzymatic hydrolysis of sun-dried cladodes resulted in a hydrolysate containing
      (per litre) 45.5 g glucose, 6.3 g xylose, 9.1 g galactose, 10.8 g arabinose and
      9.6 g fructose. Even though K. marxianus had a much higher growth rate and
      utilized l-arabinose and d-galactose more completely than C. utilis, its biomass
      yield coefficient was lower due to ethanol and ethyl acetate production despite
      aerobic cultivation. Yeast cultivation more than doubled the protein content of
      the hydrolysate, with an essential amino acid profile superior to sorghum and
      millet grains. CONCLUSIONS: This K. marxianus strain was weakly Crabtree
      positive. Despite its low biomass yield, its performance compared well with C.
      utilis. This is the first report showing that the protein content and quality of
      O. ficus-indica cladode biomass could substantially be improved by yeast
      cultivation, including a comparative evaluation of C. utilis and K. marxianus.

PMID- 25371281
TI  - Anti-inflammatory properties of resveratrol in the retinas of type 2 diabetic
      rats.
AB  - Resveratrol (trans-3,5,4'-trihydroxystilbene) is a nutritional supplement with
      anti-inflammatory properties. The present study investigated the long-term anti
      inflammatory property of resveratrol in the retinas of type 2 diabetic rats. Male
      Wistar rats were divided into four groups: normal control, diabetic control,
      resveratrol-treated normal rats and resveratrol-treated diabetic rats. Type 2
      diabetes was induced by a single dose injection of streptozotocin (50 mg/kg;
      i.p.) 15 min after the administration of nicotinamide (110 mg/kg; i.p.) in 12-h
      fasted rats (the streptozotocin-nicotinamide type 2 diabetic model). Oral
      resveratrol administration (5 mg/kg per day for 4 months) significantly improved
      glucose tolerance, and alleviated hyperglycemia and weight loss in diabetic rats.
      Furthermore, resveratrol administration significantly decreased the elevated
      levels of nuclear factor-kappaB activity, and mRNA expression, tumour necrosis
      factor alpha level and apoptotic cells in the retinas of the diabetic rats.
      Furthermore, resveratrol did not significantly affect plasma insulin levels. Long
      term resveratrol administration has beneficial anti-inflammatory properties in a
      rat model of diabetes. However, whether resveratrol exerts its effects directly
      or through reducing blood glucose levels requires further investigation. 

PMID- 25371282
TI  - Preparation of asymmetrical polyynes by a solid-supported Glaser-Hay reaction.
AB  - Polyynes exhibit both unique photophysical properties and biological activities,
      necessitating efficient syntheses towards these core structures. A novel
      methodology for the construction of highly conjugated asymmetrical polyynes has
      been developed in a chemoselective fashion utilizing a solid-support. The
      synthesis has been applied to prepare a small library of polyynes in good to
      moderate yield. Moreover, their interesting fluorescence properties have been
      investigated, demonstrating the ability to tune fluorescence through selection of
      appropriate synthetic building blocks. 

PMID- 25371283
TI  - Spatial configuration of vertically related word pairs modulates the N400
      component.
AB  - This study examined the effect of spatial iconicity on the N400 component.
      Spatial iconicity is defined as the spatial arrangement of words on a screen
      relative to the spatial arrangement of their referents (e.g. attic-basement). In
      two experiments, electroencephalograms were recorded in 32 participants while
      performing a semantic relatedness judgment task on pairs of words that were
      either related or unrelated. All of the related word pairs were parts of objects
      that shared a vertical spatial relationship. In Experiment 1, the words of each
      pair were presented simultaneously on top of one another. Results showed that
      related word pairs presented in a spatial arrangement that mismatched the spatial
      relationship of their referents were associated with increased error rates as
      well as larger N400 components known to index semantic/conceptual processing
      cost. These findings thus suggest that the words automatically activated
      visuospatial simulations of their referents and that semantic/conceptual
      processing difficulty arose when the vertical arrangement of the word pairs was
      inconsistent with those simulations. In line with this interpretation, these
      effects were not present in Experiment 2 when the words of each pair were
      presented in succession in the middle of the screen. Overall, these results
      provide evidence that perceptual simulations contribute to some of the underlying
      processes of the N400 component (see video abstract, Supplemental digital content
      1, http://links.lww.com/WNR/A304). 

PMID- 25371284
TI  - Variation in the topography of the speech production cortex verified by cortical
      stimulation and high gamma activity.
AB  - In this study, we have addressed the question of functional brain reorganization
      for language in the presence and absence of anatomical lesions in two patients
      with epilepsy using cortical stimulation mapping and high gamma (HG) activity in
      subdural grid recordings. In both, the expressive language cortex was defined as
      the cortical patch below the electrode(s) that when stimulated resulted in speech
      arrest, and during speech expression tasks generated HG activity. This patch fell
      within the borders of Broca's area, as defined anatomically, in the case of the
      patient with a lesion, but outside that area in the other, lesion-free patient.
      Such results highlight the necessity for presurgical language mapping in all
      cases of surgery involving the language-dominant hemisphere and suggest that HG
      activity during expressive language tasks can be informative and helpful in
      conjunction with cortical stimulation mapping for expressive language mapping. 

PMID- 25371285
TI  - 2014 Colorado alphaherpesvirus latency symposium.

PMID- 25371286
TI  - Comparison between biosimilar filgrastim vs other granulocyte-colony stimulating
      factor formulations (originator filgrastim, peg-filgrastim and lenograstim) after
      autologous stem cell transplantation: a retrospective survey from the Rome
      Transplant Network.

PMID- 25371287
TI  - Next-generation sequencing studies guide the design of pyrrole-imidazole
      polyamides with improved binding specificity by the addition of beta-alanine.
AB  - The identification of binding sites for small molecules in genomic DNA is
      important in various applications. Previously, we demonstrated rapid
      transcriptional activation by our small molecule SAHA-PIP. However, it was not
      clear whether the strong biological effects exerted by SAHA-PIP were attributable
      to its binding specificity. Here, we used high-throughput sequencing (Bind-n-seq)
      to determine the binding specificity of SAHA-PIPs. Sequence specificity bias was
      determined for SAHA-PIPs (3 and 4), and this showed enhanced 6 bp sequence
      specific binding compared with hairpin PIPs (1 and 2). This finding allowed us to
      investigate the role of the beta-alanine that links SAHA to PIP, and led in turn
      to the design of betabeta-PIPs (5 and 6), which showed enhanced binding
      specificity. Overall, we demonstrated the importance of beta-moieties for the
      binding specificity of PIPs and the use of cost-effective high-throughput
      screening of these small molecules for binding to the DNA minor groove. 

PMID- 25371289
TI  - Combination of the mTOR inhibitor RAD001 with temozolomide and radiation
      effectively inhibits the growth of glioblastoma cells in culture.
AB  - The present in vitro study aimed to assess the effects of combining the mTOR
      inhibitor RAD001 and temozolomide (TMZ) together with irradiation by either low
      linear energy transfer (LET) radiation (gamma-rays) or high-LET radiation (fast
      neutrons) on the growth and cell survival of the human glioblastoma cell line U
      87. We observed a strong decrease in cell proliferation along with a concomitant
      increase in cell death as a function of the radiation dose. As expected, high-LET
      radiation was more effective and induced more sustained damage to DNA than low
      LET radiation. While RAD001 in association with TMZ induced autophagic cell
      death, additional combination with either type of radiation did not further
      increase its occurrence. On the contrary, apoptosis remained at a low level in
      all experimental groups.

PMID- 25371288
TI  - A method for gene-based pathway analysis using genomewide association study
      summary statistics reveals nine new type 1 diabetes associations.
AB  - Pathway analysis can complement point-wise single nucleotide polymorphism (SNP)
      analysis in exploring genomewide association study (GWAS) data to identify
      specific disease-associated genes that can be candidate causal genes. We propose
      a straightforward methodology that can be used for conducting a gene-based
      pathway analysis using summary GWAS statistics in combination with widely
      available reference genotype data. We used this method to perform a gene-based
      pathway analysis of a type 1 diabetes (T1D) meta-analysis GWAS (of 7,514 cases
      and 9,045 controls). An important feature of the conducted analysis is the
      removal of the major histocompatibility complex gene region, the major genetic
      risk factor for T1D. Thirty-one of the 1,583 (2%) tested pathways were identified
      to be enriched for association with T1D at a 5% false discovery rate. We analyzed
      these 31 pathways and their genes to identify SNPs in or near these pathway genes
      that showed potentially novel association with T1D and attempted to replicate the
      association of 22 SNPs in additional samples. Replication P-values were skewed
      (P=9.85*10-11) with 12 of the 22 SNPs showing P<0.05. Support, including
      replication evidence, was obtained for nine T1D associated variants in genes
      ITGB7 (rs11170466, P=7.86*10-9), NRP1 (rs722988, 4.88*10-8), BAD (rs694739,
      2.37*10-7), CTSB (rs1296023, 2.79*10-7), FYN (rs11964650, P=5.60*10-7), UBE2G1
      (rs9906760, 5.08*10-7), MAP3K14 (rs17759555, 9.67*10-7), ITGB1 (rs1557150,
      1.93*10-6), and IL7R (rs1445898, 2.76*10-6). The proposed methodology can be
      applied to other GWAS datasets for which only summary level data are available.

PMID- 25371290
TI  - Exploring the diversity and metabolic potential of actinomycetes from temperate
      marine sediments from Newfoundland, Canada.
AB  - Marine sediments from Newfoundland, Canada were explored for biotechnologically
      promising Actinobacteria using culture-independent and culture-dependent
      approaches. Culture-independent pyrosequencing analyses uncovered significant
      actinobacterial diversity (H'-2.45 to 3.76), although the taxonomic diversity of
      biotechnologically important actinomycetes could not be fully elucidated due to
      limited sampling depth. Assessment of culturable actinomycete diversity resulted
      in the isolation of 360 actinomycetes representing 59 operational taxonomic
      units, the majority of which (94 %) were Streptomyces. The biotechnological
      potential of actinomycetes from NL sediments was assessed by bioactivity and
      metabolomics-based screening of 32 representative isolates. Bioactivity was
      exhibited by 41 % of isolates, while 11 % exhibited unique chemical signatures in
      metabolomics screening. Chemical analysis of two isolates resulted in the
      isolation of the cytotoxic metabolite 1-isopentadecanoyl-3beta-D-glucopyranosyl-X
      glycerol from Actinoalloteichus sp. 2L868 and sungsanpin from Streptomyces sp.
      8LB7. These results demonstrate the potential for the discovery of novel
      bioactive metabolites from actinomycetes isolated from Atlantic Canadian marine
      sediments.

PMID- 25371291
TI  - Effect of analgesia and anti-inflammatory treatment on weight gain and milk
      intake of dairy calves after disbudding.
AB  - AIM: To assess the effect of analgesia at disbudding on weight gain and milk
      intake of dairy calves. METHODS: Four disbudding protocols were used on 3- to 6
      week-old Friesian-Jersey calves. Farm staff disbudded 101 calves without sedation
      or local analgesia, of which 51 received 20 mg meloxicam S/C. Veterinary staff
      disbudded 101 calves with sedation and local analgesia, of which 51 also received
      20 mg meloxicam S/C. Calves were weighed before disbudding, 15 and 30 days later,
      and individual milk consumption was recorded for 11 days. Daily weight gain and
      milk consumption were analysed using mixed models and ANOVA. RESULTS: From
      disbudding (Day 0) to Day 15 farmer-disbudded calves receiving meloxicam grew
      faster (0.65 kg/day) than calves without meloxicam (0.55 kg/day; p=0.011), but an
      interaction between operator and meloxicam treatment (p=0.056) meant that
      meloxicam treatment did not increase growth rates in veterinary-disbudded calves
      (0.63 vs. 0.64 kg/day; p=0.872). From Days 16-30 there was no significant effect
      of meloxicam on growth rate, but veterinarian-disbudded calves grew faster (0.76
      kg/day) than farmer-disbudded calves (0.66 kg/day; p=0.034). Overall, for the
      first 30 days after disbudding, if meloxicam was not used', veterinarian
      disbudded calves grew faster than farmer-disbudded calves (p=0.002). However if
      meloxicam was used at disbudding there was no difference in growth rate between
      veterinarian- and farmer-disbudded calves (p=0.878). Mean cumulative milk
      consumption for the 11 days after disbudding was greater for calves disbudded by
      veterinary staff than by farm staff (p<0.001), but there was no effect of
      meloxicam treatment (p=0.618) and no interaction with operator (p=0.86) on
      cumulative milk consumption. CONCLUSIONS: Three to 6-week-old dairy calves
      disbudded by farm staff with no analgesia grew significantly slower over the next
      15 days than farmer-disbudded calves given meloxicam, and slower over the next 30
      days than veterinarian-disbudded calves given xylazine and lignocaine. However
      addition of meloxicam to the latter protocol had no effect on growth rate. Milk
      intake was significantly higher for 11 days for veterinarian- compared with
      farmer-disbudded calves. CLINICAL RELEVANCE: This study adds to the evidence that
      analgesia during disbudding is beneficial for calf productivity as well as calf
      welfare.

PMID- 25371292
TI  - Small angle X-ray scattering coupled with in situ electromechanical probing of
      nanoparticle-based resistive strain gauges.
AB  - A comprehensive study on the electromechanical behavior of nanoparticle-based
      resistive strain gauges in action through normal and grazing incidence small
      angle X-ray scattering (SAXS/GISAXS) investigations is presented. The strain
      gauges were fabricated from arrays of colloidal gold nanoparticle (NP) wires
      assembled on flexible polyethylene terephthalate and polyimide substrates by
      convective self-assembly. Microstructural changes (mean interparticle distance
      variations) within these NP wires under uniaxial stretching estimated by
      SAXS/GISAXS are correlated to their macroscopic electrical resistance variations.
      SAXS measurements suggest a linear longitudinal extension and transversal
      contraction of the NP wires with applied strain (0 to ~ 13%). The slope of this
      longitudinal variation is less than unity, implying a partial strain transfer
      from the substrate to the NP wires. The simultaneously measured electrical
      resistance of the strain gauges shows an exponential variation within the elastic
      domain of the substrate deformation, consistent with electron tunnelling through
      the interparticle gaps. A slower variation observed within the plastic domain
      suggests the formation of new electronic conduction pathways. Implications of
      transversal contraction of the NP wires on the directional sensitivities of
      strain gauges are evaluated by simulating electronic conduction in models
      mimicking a realistic NP arrangement. A loss of directionality of the NP-based
      strain gauges due to transversal current flow within the NP wires is deduced.

PMID- 25371294
TI  - Rational dissection of a high institutional cesarean section rate: an analysis
      using the Robson Ten Group Classification System.
AB  - AIM: Cesarean section (CS) rates have risen far in excess of the optimal 15%
      recommended by the World Health Organization. The Robson Ten Group Classification
      System (TGCS) allows meaningful analysis of a CS rate. The aim of this study is
      to identify the leading patient categories contributing to our institution's CS
      rate. METHODS: Prospective study of all women who delivered at the Singapore
      General Hospital from January 2008 to December 2011. The following data was
      recorded: parity, singleton/multiple pregnancy, previous CS, mode of labor onset
      and gestational age at delivery. CS rates were computed for each group, as well
      as their relative contribution to the overall CS rate. RESULTS: There were 6074
      deliveries, in which 2011 (33.1%) women had CS delivery. Group 5 was the largest
      contributor to the overall CS rate (25.9%). Of the patients in this group, 18.8%
      had a successful vaginal birth after cesarean (VBAC). Group 2 was the second
      largest contributor to the overall CS rate at 18.0%. Group 10 had a high
      contribution of 16.1%. CONCLUSION: The TGCS allows easy identification of the
      leading contributing patient groups. The surprisingly high contribution of group
      10 suggests that our institution, a tertiary multidisciplinary teaching hospital,
      manages a sizeable group of high-risk patients in its obstetric case mix
      accounting for the high CS rate. Almost one in five term pregnancies with one
      previous CS had a successful vaginal delivery, suggesting that the institutional
      attempted VBAC rate is higher than 20%.

PMID- 25371293
TI  - Trends in dental service provision in Australia: 1983-1984 to 2009-2010.
AB  - OBJECTIVE: To investigate time trends in dental service provision. METHODS: A
      random sample of Australian dentists was surveyed by mailed questionnaires in
      1983-1984, 1993-1994, 2003-2004, and 2009-2010 (response rates 67-76%). The
      service rate per visit was collected from a log of services. RESULTS: The rate of
      service provision per visit [rate ratio (RR)] increased from 1983-1984 to 2009
      2010 for the service areas of diagnostic (RR=1.8; 1.6-1.9), preventive (RR=1.9;
      1.6-2.1), endodontic (RR=2.1; 1.7-2.6), and crown and bridge (RR=2.9; 2.3-3.8),
      whereas prosthodontic services decreased (RR=0.7; 0.6-0.9). CONCLUSIONS: The
      profile of services provided by dentists changed over the study period to include
      less emphasis on replacement of teeth and more on diagnosis, prevention, and
      retention of natural dentitions.

PMID- 25371295
TI  - Targeting solid tumours with potassium channel activators. A return to
      fundamentals?
AB  - From a pharmacological point of view nicotinamide and minoxidil are potassium
      channel activators. Nicotinamide is used as a radiosensitizer in ARCON
      (accelerated radiotherapy combined with carbogen breathing and nicotinamide)
      therapeutic strategy with promising results but not confirmed so far. Minoxidil
      has never been considered by radiotherapists. Based from recent
      pathophysiological considerations we suggest a new perspective for the use of
      these two "old" molecules in order to target solid tumours. 

PMID- 25371296
TI  - Formulation, characterization, and in vitro/vivo studies of aclacinomycin A
      loaded solid lipid nanoparticles.
AB  - OBJECTIVE: The aim of this study was to prepare aclacinomycin A (ACM)-loaded
      solid lipid nanoparticles (SLNs) and to evaluate their in vitro and in vivo
      characteristics. METHODS: SLNs were prepared using an emulsion evaporation
      solidification method, and characterized in accordance with the morphological
      examination, particle size distribution, entrapment efficiency, drug-loading, and
      in vitro release. Pharmacokinetic and biodistribution studies were employed to
      evaluate the in vivo of SLNs. RESULTS: The SLNs were spherical in shape, uniform
      in size, and appropriate for administration via intravenous injection. The drug
      content, encapsulation efficiency, and drug loading of prepared SLNs were 96.4%
      +/- 4.6%, 86.7% +/- 2.3%, and 4.8% +/- 0.7% (n = 3), respectively, and the mean
      diameter was 68.2 +/- 5.6 nm from three batches. The SLNs were produced with
      stable physical properties and demonstrated significantly sustained release. The
      pharmacokinetic behavior of ACM was greatly improved by lyophilized injection of
      SLN with sustained drug release and high bioavailability. In addition, the
      results obtained from tissue distribution showed that ACM-SLNs were hepatic
      targeting in vivo. CONCLUSIONS: The present work demonstrated the feasibility of
      liver-targeted delivery of ACM utilizing SLNs.

PMID- 25371297
TI  - Preventing inguinodynia after hernia surgery: does the type of mesh matter?

PMID- 25371298
TI  - The selective use of laparoscopic repair is safe in high-risk patients suffering
      from perforated peptic ulcer.
AB  - BACKGROUND: The use of laparoscopic repair for perforated peptic ulcer (PPU) was
      shown to be safe and recommended in low-risk patients. However, whether the
      approach is safe to apply to high-risk patients is uncertain. STUDY DESIGN: This
      was a retrospective study of all patients with PPU admitted between January 2002
      and December 2012. The laparoscopy-first approach (LFA) was adopted as a routine
      for all patients. The outcomes of LFA for PPU were reviewed and assessed to
      determine if the approach was safe in high-risk patients. RESULTS: Three hundred
      and seventy three patients that suffered from PPU were included into the study
      and 50.9% received laparoscopic repair. There was a significant increase in the
      number of operations performed yearly by the LFA (P < 0.001). 25.2% of the
      patients had a Boey score of >=2. High-risk patients that received LFA suffered
      from larger ulcers (P < 0.001) with more severe contamination (P = 0.006) that
      required conversion (P = 0.002) when compared to the low-risk patients. When
      compared to open surgery, more high-risk patients in the open group had ASA grade
      >=3 (P = 0.007) and suffered from mortality (P = 0.001). The only significant
      predictor to mortality in high-risk patients was ASA grade >=3 (P = 0.014).
      CONCLUSIONS: The adoption of LFA in patients suffering from PPU was associated
      with acceptable rates of mortality and morbidity. The approach could also be
      selectively adopted in patients with Boey score >=2 provided their ASA grading is
      low and hemodynamically stable.

PMID- 25371299
TI  - Two-day hospital stay after laparoscopic colorectal surgery: is enhanced recovery
      program a healthcare system-specific issue?

PMID- 25371300
TI  - Transfusion-related adverse reactions reported to the National Healthcare Safety
      Network Hemovigilance Module, United States, 2010 to 2012.
AB  - BACKGROUND: In 2010, health care facilities in the United States began voluntary
      enrollment in the National Healthcare Safety Network (NHSN) Hemovigilance Module.
      Participants report transfusion practices; red blood cell, platelet (PLT),
      plasma, and cryoprecipitate units transfused; and transfusion-related adverse
      reactions and process errors to the Centers for Disease Control and Prevention
      through a secure, Internet-accessible surveillance application available to
      transfusing facilities. STUDY DESIGN AND METHODS: Facilities submitting at least
      1 month of transfused components data and adverse reactions from January 1, 2010,
      to December 31, 2012, were included in this analysis. Adverse reaction rates for
      transfused components, stratified by component type and collection and
      modification methods, were calculated. RESULTS: In 2010 to 2012, a total of 77
      facilities reported 5136 adverse reactions among 2,144,723 components transfused
      (239.5/100,000). Allergic (46.8%) and febrile nonhemolytic (36.1%) reactions were
      most frequent; 7.2% of all reactions were severe or life-threatening and 0.1%
      were fatal. PLT transfusions (421.7/100,000) had the highest adverse reaction
      rate. CONCLUSION: Adverse transfusion reaction rates from the NHSN Hemovigilance
      Module in the United States are comparable to early hemovigilance reporting from
      other countries. Although severe reactions are infrequent, the numbers of
      transfusion reactions in US hospitals suggest that interventions to prevent these
      reactions are important for patient safety. Further investigation is needed to
      understand the apparent increased risk of reactions from apheresis-derived blood
      components. Comprehensive evaluation, including data validation, is important to
      continued refinement of the module.

PMID- 25371301
TI  - MicroRNAs: powerful regulators and potential diagnostic tools in cardiovascular
      disease.

PMID- 25371302
TI  - Rare cardiovascular diseases: from European legislations to classification and
      clinical practice.

PMID- 25371303
TI  - Effect of complex cardiac rehabilitation on physical activity and quality of life
      during long-term follow-up after surgical correction of congenital heart disease.
AB  - BACKGROUND: Comprehensive cardiac rehabilitation (CCR) is an important element of
      the comprehensive management of grown-up congenital heart disease (GUCH) patients
      after surgical correction of congenital heart disease (CHD) but access to this
      treatment is still limited. We still lack Polish guidelines on CCR, including
      controlled training in young adults several years after surgical correction of
      CHD. AIM: To assess the effect of a CCR program on physical capacity, exercise
      tolerance, quality of life, and severity of depressive symptoms in GUCH patients
      long-term after surgical correction of CHD. METHODS: We studied 57 CHD patients
      (30 females, 27 males, mean age 23 +/- 3.4 years) at least 12 months after
      surgical correction of a ventricular septal defect (VSD) or ostium secundum
      atrial septal defect (ASD II). All patients were offered a CCR program, and 31 of
      them participated (rehabilitation group [Reh]) and 26 refused (non-rehabilitated
      group [NReh]). All patients underwent baseline cardiopulmonary exercise testing
      (CPET) using a cycloergometer and a ramp protocol with an initial load of 20 W
      followed by 10 W load increments per minute. Psychological evaluation included
      the Beck Depression Inventory (BDI) and the Euro QoL 5D questionnaire to evaluate
      quality of life. Patients were reassessed 30 days after the initial evaluation
      using the same investigations. RESULTS: During CPET, all patients reached peak
      exercise intensity at the level of 15-17 in the Borg scale without complications.
      Resting HR was lower in the Reh group (74 +/- 8 bpm) compared to the NReh group
      (81 +/- 14 bpm). During CPET, patients in the Reh group reached significantly
      higher peak HR and percent maximum HR. Workload increased nonsignificantly (144 W
      vs. 124 W, p = 0.121), while duration of exercise and peak oxygen consumption was
      significantly longer in the Reh group compared to the NReh group (14 min vs. 11
      min, p = 0.001; and 27.5 mL/kg/min vs. 23 mL/kg/min, p = 0.003, respectively).
      Patients in the NReh group showed non significantly higher severity of depressive
      symptoms compared to the Reh group, as evaluated using BDI at 30 days (mean score
      4.8 vs. 2.2, respectively, p = 0.59). In contrast, subjectively and objectively
      rated quality of life was significantly higher in the Reh group compared to the
      NReh (score 89 vs. 74.4, p < 0.01; and 94 vs. 83, p < 0.01, respectively).
      CONCLUSIONS: Implementation of a CCR program improves physical capacity, exercise
      tolerance, and quality of life and reduces depressive symptoms in patients late
      after surgical correction of CHD. Introduction of such programs seems reasonable
      as a supplement to the holistic care for GUCH patients.

PMID- 25371304
TI  - Shepherd's crook right coronary artery: a multidetector computed tomography
      coronary angiography study.
AB  - BACKGROUND: Shepherd's crook deformity of the right coronary artery (RCA) is
      considered a haemodynamically non-significant course anomaly. It may be
      challenging for cardiologists during percutaneous transluminal coronary
      angioplasty. AIM: To investigate the radiological anatomy of the high riding
      course of the proximal segment of the RCA, especially focused on the Shepherd's
      crook RCA (SCRCA), on multidetector computed tomography (MDCT) coronary
      angiography. METHODS: A total of 1,118 MDCT coronary angiography examinations
      were reviewed retrospectively (349 [31.2%] male; 769 [68.8%] female, age range
      from 18 to 88 years [54.4 +/- 14.7 years, mean +/- standard deviation]). We
      classified the segments that had a higher course than RCA ostium (high riding
      RCA) into two types: type 1--courses turning inferior with an angle equal to or
      more than 90 degrees, type 2 (SCRCA)--courses turning inferior with an angle less
      than 90 degrees. The origin of the sinoatrial node artery (SANA) and conus artery
      were also noted. RESULTS: High riding RCA was detected in 146 (13%) patients. Of
      them, 105 (71%) had type 1 and 41 (29%) had type 2. Atherosclerotic plaque
      formations, to varying degrees, were presented in 10 (24.3%) of the patients with
      SCRCA. Approximately half of SANA originated from the SCRCA segment of the RCA in
      SCRCA cases. CONCLUSIONS: This is the first study about SCRCA that has been
      performed with MDCT coronary angiography. This study brings important anatomical
      knowledge to cardiologists. To have knowledge about the origin of the SANA prior
      to PTCA procedures is important to prevent possible arrhythmias and infarcts.

PMID- 25371305
TI  - The relationship between fragmented QRS complexes and SYNTAX and Gensini scores
      in patients with acute coronary syndrome.
AB  - BACKGROUND: Fragmented QRS (fQRS) complexes on 12-lead electrocardiography (ECG)
      have been reported to be predictors of cardiac events and all-cause mortality in
      coronary artery disease (CAD). AIM: To investigate the relationship between fQRS
      complexes and SYNTAX and Gensini scores in patients with acute coronary syndrome
      (ACS). METHODS: A total of 302 patients (223 men and 79 women) with ACS (133 ST
      elevated myocardial infarction [STEMI], 107 non-STEMI [NSTEMI], and 62 unstable
      angina pectoris [USAP]) were evaluated retrospectively in this study. An fQRS
      pattern was found in 70 patients (fQRS group) but was not found in 232 patients
      (non-fQRS group). SYNTAX score > 22 and Gensini score > 20 were defined as high
      SYNTAX and Gensini scores. The relationship between the presence of fQRS on 12
      lead ECG and SYNTAX and Gensini scores was assessed. RESULTS: SYNTAX score (p <
      0.001), Gensini score (p < 0.001), NYHA class (p < 0.001), QRS duration (p <
      0.001), number of disease vessels (p = 0.003), and high sensitive troponin T
      levels (p = 0.026) were significantly higher in the fQRS group. The number of
      fQRS leads (HR 5.79, 95% CI 2.78-12.06, p < 0.001, HR 3.41, 95% CI 1.32-8.78, p =
      0.016, respectively) was found to be an independent predictor of high SYNTAX
      score and high Gensini score in multivariate analysis. CONCLUSIONS: The number of
      fQRS leads on 12-lead ECG on admission is associated with the severity and
      complexity of CAD in patients with ACS.

PMID- 25371306
TI  - Influence of folic acid supplementation on coagulation, inflammatory, lipid, and
      kidney function parameters in subjects with low and moderate content of folic
      acid in the diet.
AB  - BACKGROUND: The human body requires folic acid (FA) to produce blood cells,
      secure cell division, and growth. Moreover, this vitamin is important in the
      prevention of cardiovascular disease (CVD). Because the results of studies on the
      use of FA in the prevention of CVD are ambiguous, it seems necessary to conduct
      further research, which will explain in which cases supplementation is effective.
      AIM: To assess the impact of FA supplementation on the coagulation, inflammatory,
      lipid parameters, and kidney function in subjects with atherosclerosis risk
      factors, depending on the content of FA in their diet. METHODS: The study
      enrolled 97 young adult Caucasian individuals (34 males and 63 females) with
      atherosclerosis risk factors. This population was divided into two groups: A-
      with low content of FA in the diet (< 40% of reference daily intake) and B--with
      moderate content of FA in the diet (40-90% of reference daily intake). The
      participants were asked to take FA in the low-dose of 0.4 mg/24 h for 3 months.
      RESULTS: Low-dose FA supplementation resulted in elevation of FA concentrations
      (79% vs. 75.1%) in the studied groups and, concomitantly, a decrease in
      homocysteine concentrations (21% vs. 20.3%). Mean level of creatinine decreased
      after FA supplementation in both groups (0.93 +/- 1.1 vs. 0.72 +/- 0.15 mg/dL and
      0.83 +/- 0.16 vs. 0.77 +/- 0.15 mg/dL). These differences were statistically
      significant (p < 0.0001). The difference in mean estimated glomerular filtration
      rate values before and after FA supplementation was statistically significant in
      group A (p = 0.002) and on the border of statistical significance in group B (p =
      0.06). CONCLUSIONS: FA supplementation has no influence on the coagulation,
      inflammatory and lipid parameters in subjects with atherosclerosis risk factors
      depending on the content of FA in their diet. However FA supplementation may have
      a beneficial effect on kidney function in subjects with low content of FA in the
      diet.

PMID- 25371307
TI  - Incidence, treatment, in-hospital mortality and one-year outcomes of acute
      myocardial infarction in Poland in 2009-2012--nationwide AMI-PL database.
AB  - BACKGROUND AND AIM: Nationwide data on acute myocardial infarction (AMI) are
      available for some Western but not for Central and Eastern European countries. We
      performed a study on nationwide data of all Polish AMI patients in 2009-2012 to
      assess incidence, quality of care, and cardiovascular events during 1 year
      following AMI. METHODS: The database of the only public, obligatory health
      insurer in Poland (National Health Fund) together with data from the Central
      Statistical Office were used. AMI cases were selected based on primary diagnosis
      ICD-10 codes I21-I22. For years 2009-2012, index hospitalisations (n = 311,813)
      in a given year and death records were analysed. Additionally, data on
      hospitalisations, procedures and deaths during 1 year follow-up were obtained for
      2009. RESULTS: Age-adjusted incidence of AMI in Poland in 2009 was 196 cases per
      100,000 population (176 per 100,000 were hospitalised), with a decreasing trend
      over time. The incidence was 2.5 times higher in men than in women. The median
      age was 63 years in men and 74 years in women. The proportion of ST elevation
      myocardial infarction (STEMI) decreased from 59% to 48% in 2012, and the
      proportion of patients receiving invasive treatment increased from 72% to 81%.
      Age-adjusted case fatality rate was equal in women and men. In 2009, the number
      of patients with AMI was 75,054 (61% men, 39% women) and 83% of them were treated
      in cardiology units. Invasive strategy was used in 77% of patients with STEMI and
      66% of those with non-STEMI, thrombolysis in 1% and coronary artery bypass
      grafting in 1.9% of patients. Invasive treatment was used less frequently in
      women and the elderly patients. When all hospitals where a patient was treated
      until the final discharge were taken into account, in-hospital mortality was
      10.5%. The lowest in-hospital mortality was noted among patients treated
      invasively (6.3%). The total number of readmissions within 1 year following AMI
      was 84,718, of which 61.9% were due to cardiovascular causes. The most common
      causes were stable coronary artery disease (27%), heart failure (7.9%), recurrent
      infarction (7.0%), and unstable angina (6.8%). Within 1 year after AMI, only 22%
      of patients participated in a cardiac rehabilitation programme. Total 1-year
      mortality was 19.4% (invasive treatment 12.3%, non-invasive treatment 38.0%).
      CONCLUSIONS: Standards of care and early outcomes in AMI in Poland are similar to
      Western countries. The major cause of higher mortality due to AMI in the Polish
      population is a high incidence of AMI, indicating a need for intensification of
      primary prevention programmes. Secondary prevention is also underused, especially
      in the field of cardiac rehabilitation.

PMID- 25371308
TI  - Association of genetic variation in the natriuretic peptide system and left
      ventricular mass and blood pressure in newborns.
AB  - BACKGROUND: The natriuretic peptides play a key role in the modulation of left
      ventricular mass (LVM) and blood pressure (BP). We hypothesised that NPPA
      (natriuretic peptide precursor A gene), NPPB (natriuretic peptide precursor B
      gene), and NPPC (natriuretic peptide precursor C gene) are candidate genes
      possibly involved in the development or modulation of LVM at early life. AIM: To
      assess the relationship between NPPA, NPPB, and NPPC gene polymorphisms with LVM
      and BP in newborns. METHODS: A total of 206 healthy newborns were studied by two
      dimensional M-mode echocardiography. The polymorphisms NPPA rs5065, NPPB
      rs198389, and NPPC rs5268 were characterised. RESULTS: Newborns carrying the C
      allele of the NPPB polymorphism had significantly lower LVM/body surface area
      (BSA) and LVM/body weight (BW) values when compared with newborns' homozygotes
      for the T allele (41.76 g/m2 vs. 48.31 g/m2, p adjusted = 0.044 and 2.78 g/kg vs.
      3.26 g/kg, p adjusted = 0.031, respectively). An association was observed between
      NPPA genotype and systolic BP, diastolic BP, and mean arterial pressure >= 90th
      percentile (p = 0.029, p = 0.0048, p = 0.004, respectively). Also an association
      was observed for systolic BP >= 90th percentile for NPPB (p = 0.016).
      CONCLUSIONS: The present study shows that the NPPB gene polymorphism is
      associated with modulation of LVM in newborns. The NPPA and NPPB gene
      polymorphisms are associated with BP.

PMID- 25371309
TI  - Application of microvolt T-wave alternans testing in scheduling implantable
      cardioverter-defibrillator placement for the primary prevention of sudden cardiac
      death in patients with left ventricular dysfunction.
AB  - BACKGROUND: Patients with left ventricular ejection fraction (LVEF) <= 35% are
      eligible for implantable cardioverter-defibrillator (ICD) placement for the
      primary prevention of sudden cardiac death (SCD). This recommendation results in
      continuously growing waiting lists of patients who have been qualified for and
      are awaiting the procedure. Whiled reduced LVEF is a feature shared by all the
      patients in this group, the risk of malignant ventricular arrhythmias varies
      widely. It therefore seems important from the clinical point of view to improve
      the waiting lists by identifying patients at the lowest risk of SCD, who can
      safely wait for the procedure, while higher-risk patients undergo the procedure
      before them. AIM: To verify the utility of microvolt T-wave alternans (MTWA)
      testing, which is characterised by high negative predictive value (NPV), in
      scheduling ICD implantation in these patients. METHODS: The study included 152
      patients with LVEF <= 35%, qualified for ICD implantation for the primary
      prevention of SCD, and managed in accordance with the current recommendations.
      Patients with a history of malignant ventricular arrhythmias were excluded. Each
      patient underwent MTWA testing during chronic treatment (including beta-blockers)
      and was followed-up. RESULTS: During 14 +/- 8 months of follow-up, the primary
      outcome, which included SCD, non-fatal sustained ventricular arrhythmia, or
      appropriate high-voltage ICD discharge, was observed in 16 patients. The one-year
      event rate was 13.1% (5.8-19.8%) in non-negative MTWA patients and 0% in those
      who had negative MTWA result (p = 0.027). The NPV of the MTWA test was 100% (95%
      CI 92.73- 00%). CONCLUSIONS: In the group of patients with left ventricular
      systolic dysfunction, excluding patients with a history of malignant ventricular
      arrhythmia, the NPV of MTWA was 100% over 12 months of observation. MTWA may
      therefore be considered useful in determining the order of ICD implantation
      procedures in this group of patients by identifying patients at a relatively low
      risk of malignant ventricular arrhythmias, who can be relatively safely
      rescheduled for ICD implantation at a later time. Future studies should
      concentrate on this issue.

PMID- 25371310
TI  - Impact of coronary artery disease presence on the long-term follow-up of carotid
      artery stenting.
AB  - BACKGROUND: Carotid artery stenting (CAS) has become an alternative for carotid
      endarterectomy in the treatment of carotid artery atherosclerosis, due to limited
      injury and comparable periprocedural risk. The impact of coronary artery disease
      (CAD) on long-term follow-up after CAS needs to be reconsidered due to the
      intensification of aggressive pharmacotherapy in CAD in recent years. AIM: To
      assess the impact of CAD presence on the long-term follow-up of patients after
      CAS. METHODS: Data of 130 symptomatic and asymptomatic patients undergoing CAS
      with cerebral protection systems from December 2002 to December 2010 were divided
      into two groups: those with and those without CAD. Major adverse cardio- and
      cerebrovascular events (MACCE) during follow-up were defined as the combination
      of death (cardiac and non-cardiac), myocardial infarction (MI) and stroke or
      transient ischaemic attack (TIA). Long-term outcomes of patients were stratified
      based on the history of CAD. RESULTS: The mean age of patients was 66 +/- 9
      years, and the majority of patients were male (80.2%). Long-term follow-up data
      were available in 86.2% of patients. During mean follow-up of 71.9 +/- 31.7
      months the all-cause mortality rate was 19.3%. The rates of MI, stroke/TIA, and
      MACCE were 16.7%, 12.3%, and 36.3%, respectively. The frequency of MACCE during
      long-term follow-up was higher in patients with CAD vs. without CAD (40.8% vs.
      6.7%, p = 0.01), and the mortality rate in the two groups was 22.2% vs. 0%, (p =
      0.07), respectively. CONCLUSIONS: Patients with symptomatic or asymptomatic
      carotid stenosis are high-risk individuals. The presence of CAD increases the
      risk of MACCE in such patients during long-term follow-up.

PMID- 25371311
TI  - Aortic valve replacement with a novel anti-calcification technology platform.
AB  - BACKGROUND AND AIM: The primary cause of long-term failure of bioprosthetic
      valves is structural valve deterioration due to tissue calcification. A novel
      anti-calcification technology platform was developed that may irreversibly block
      calcium binding sites in bioprosthetic valves. METHODS: Twenty patients with
      severe aortic stenosis underwent isolated aortic valve replacement using a
      bioprosthetic valve treated with the novel anti-calcification technology. Mean
      patient age and body mass index was 73.7 +/- 4.8 years and 30.1 +/- 5.8 kg/m2,
      respectively. Females comprised 65% of the patient population, and 30% of the
      population was in New York Heart Association class III/IV. Other baseline
      characteristics included hypertension (90%), hyperlipidaemia (75%), diabetes
      (35%), renal failure (25%), pulmonary disease (10%), and myocardial infarction
      (10%). Patients were followed-up for up to one year. Haemodynamic performance was
      evaluated by echocardiography. All complications were recorded. RESULTS: There
      was one early death on postoperative day five. No other complications were noted
      up to discharge. Follow-up at 3-6 months and at one year were both 100%. At one
      year, no valve-related mortality, structural valve deterioration, major
      paravalvular leak (> 2+), thromboembolic events, major bleeding, prosthetic valve
      endocarditis, or reoperation were observed. Mean effective orifice area increased
      from 1.0 +/- 0.5 cm2 at baseline to 1.8 +/- 0.5 cm2 at one year. Mean gradient
      decreased from 54.8 +/- 21.2 mm Hg at baseline to 11.3 +/- 3.4 mm Hg at one year.
      CONCLUSIONS: This early clinical experience using an aortic bioprosthetic valve
      treated with a novel anti-calcification tissue processing technology demonstrated
      excellent valve performance, durability, and safety. No valve-related
      complications were noted. Longer-term follow-up is needed to verify these
      promising results.

PMID- 25371312
TI  - Safety and biocompatibility of a novel self-expanding nitinol carotid stent with
      hybrid cell design in a porcine model of neointimal hyperplasia.
AB  - BACKGROUND: Stent design may influence the outcomes, suggesting that adverse
      event rates vary according to free cell area and cell design. Open cell design
      technology of self-expandable stents, dedicated for carotid revascularisation has
      better deliverability, although closed cell technology is expected to cause fewer
      thromboembolic events. AIM: To evaluate the feasibility and vascular response of
      novel, hybrid cell, self-expandable nitinol stents (MER(r), Balton, Poland)
      implanted into porcine carotid arteries. Hybrid cell design combines open and
      closed cell technology. METHODS: All tested stents were implanted with 10%
      overstretch into 10 carotid segments of Polish domestic pigs. Control angiography
      was obtained immediately before and after vascular interventions as well as 28
      days after the procedure. Thereafter, animals were sacrificed, and the treated
      segments were harvested and evaluated in the independent histopathology
      laboratory. RESULTS: All stents were easily introduced and implanted, showing
      good angiographic acute outcome. At 28 days, in the angiography, all vessels were
      patent with no signs of thrombi or excessive neointimal formation, with the late
      lumen loss of -0.11 +/- 0.3 mm and percentage diameter stenosis 10.18 +/- 8.1%.
      There was a 10% increase in the vessel reference diameter when compared to
      baseline (4.57 +/- 0.5 vs. 4.96 +/- 0.3 mm, p < 0.01). In the histopathology,
      mean area stenosis was 17.4% and mean intimal thickness was 0.20 mm. At
      histopathology, the mean injury, inflammation, and fibrin scores were low.
      Endothelialisation was complete in all stents, and neointimal tissue appeared
      moderately mature as shown by the moderate mean neointimal smooth muscle score.
      Nonetheless, histopathology shows one stent affected by peri-strut granulomas and
      one stent affected by marked mineralisation. CONCLUSIONS: The novel Polish self
      expandable nitinol carotid stent with hybrid cell technology shows optimal
      biocompatibility and a vascular healing profile, and therefore may be introduced
      for first-in-man application.

PMID- 25371314
TI  - Distinct dysregulation of the small leucine-rich repeat protein family in
      osteoarthritic acetabular labrum compared to articular cartilage.
AB  - OBJECTIVE: Articular cartilage is well studied in osteoarthritis (OA). However,
      the role of supporting structures, such as the acetabular labrum, a sealing
      structure surrounding the hip joint, has been investigated much less. We recently
      showed that fibrochondrocytic labrum cells are metabolically active. This study
      was undertaken to investigate hip OA-associated changes in human acetabular
      labrum cells. METHODS: Microarray analysis was performed to compare OA labrum
      cells to healthy labrum cells cultured in a 3-dimensional alginate bead system.
      Data were analyzed by cluster analysis using gene set enrichment analysis
      software and by gene list analysis using PANTHER gene family tools. Selected
      candidates were validated by quantitative polymerase chain reaction analysis on
      labrum and cartilage samples and by immunohistochemistry. The functional impacts
      of the genes identified were investigated by in vitro stimulation experiments in
      labrum cells. RESULTS: Pathway analysis revealed increased cytokine and chemokine
      signaling in OA labrum cells, whereas reduced extracellular matrix interactions
      and transforming growth factor beta signaling were observed. Several genes were
      significantly differentially expressed in OA compared to healthy labrum. We
      specifically focused on 3 small leucine-rich repeat proteins (SLRPs),
      osteomodulin, osteoglycin, and asporin, that appeared to be distinctly regulated
      in OA labrum compared to OA cartilage. SLRPs were strongly down-regulated in OA
      labrum but up-regulated in OA articular chondrocytes. Moreover, in vitro
      stimulation with osteomodulin increased aggrecan expression in OA labrum cells.
      CONCLUSION: OA labrum fibrochondrocytes have several features similar to OA
      chondrocytes. However, SLRP expression seems to be differentially influenced by
      degeneration in OA labrum compared to cartilage, suggesting a specific role for
      this supporting structure in OA. The functional impact of SLRPs on labrum cells
      makes them interesting targets for further studies in hip OA.

PMID- 25371313
TI  - The ability of the 2013 American College of Cardiology/American Heart Association
      cardiovascular risk score to identify rheumatoid arthritis patients with high
      coronary artery calcification scores.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) have increased risk of
      atherosclerotic cardiovascular disease that is underestimated by the Framingham
      Risk Score (FRS). We undertook this study to test the hypothesis that the 2013
      American College of Cardiology/American Heart Association (ACC/AHA) 10-year risk
      score would perform better than the FRS and the Reynolds Risk Score (RRS) in
      identifying RA patients known to have elevated cardiovascular risk based on high
      coronary artery calcification (CAC) scores. METHODS: Among 98 RA patients
      eligible for risk stratification using the ACC/AHA risk score, we identified 34
      patients with high CAC (defined as >=300 Agatston units or >=75th percentile of
      expected coronary artery calcium for age, sex, and ethnicity) and compared the
      ability of the 10-year FRS, RRS, and ACC/AHA risk scores to correctly assign
      these patients to an elevated risk category. RESULTS: All 3 risk scores were
      higher in patients with high CAC (P < 0.05). The percentage of patients with high
      CAC correctly assigned to the elevated risk category was similar among the 3
      scores (FRS 32%, RRS 32%, ACC/AHA risk score 41%) (P = 0.223). The C statistics
      for the FRS, RRS, and ACC/AHA risk score predicting the presence of high CAC were
      0.65, 0.66, and 0.65, respectively. CONCLUSION: The ACC/AHA 10-year risk score
      does not offer any advantage compared to the traditional FRS and RRS in the
      identification of RA patients with elevated risk as determined by high CAC. The
      ACC/AHA risk score assigned almost 60% of patients with high CAC to a low risk
      category. Risk scores and standard risk prediction models used in the general
      population do not adequately identify many RA patients with elevated
      cardiovascular risk.

PMID- 25371315
TI  - Decision-making skills in ASD: performance on the Iowa Gambling Task.
AB  - Decision making plays a key role in daily function, but little is known regarding
      how individuals with autism spectrum disorder (ASD) make decisions. The present
      studies examined decision making in persons with ASD using the Iowa Gambling Task
      (IGT), a computerized card game with the goal of earning money by deciding among
      decks of cards. To be successful, players need to figure out which decks are
      associated with winning and which are associated with losing money in the long
      run. Results of Study 1 indicated that participants with ASD made poorer
      decisions and showed slower learning of which decks earned more money compared
      with participants with typical development. Additionally, they made more frequent
      shifts between decks compared with participants with typical development. In
      Study 2, undergraduate students with typical development completed the IGT to
      examine whether instructing them to make frequent shifts between decks early in
      the IGT would negatively impact their decision making. Results of Study 2
      suggested that when participants with typical development were required to make
      frequent shifts, they exhibited a slower rate of learning and poorer decision
      making, thus emulating participants with ASD in Study 1. The combined results
      suggest that the way that persons with ASD explore and attend to their
      environment may be related to poor decision making. Implications for cognitive
      learning styles are discussed.

PMID- 25371316
TI  - Culturable diversity and functional annotation of psychrotrophic bacteria from
      cold desert of Leh Ladakh (India).
AB  - To study culturable bacterial diversity under subzero temperature conditions and
      their possible functional annotation, soil and water samples from Leh Ladakh
      region were analysed. Ten different nutrient combinations were used to isolate
      the maximum possible culturable morphotypes. A total of 325 bacterial isolates
      were characterized employing 16S rDNA-Amplified Ribosomal DNA Restriction
      Analysis with three restriction endonucleases AluI, MspI and HaeIII, which led to
      formation of 23-40 groups for the different sites at 75 % similarity index,
      adding up to 175 groups. Phylogenetic analysis based on 16S rRNA gene sequencing
      led to the identification of 175 bacteria, grouped in four phyla, Firmicutes (54
      %), Proteobacteria (28 %), Actinobacteria (16 %) and Bacteroidetes (3 %), and
      included 29 different genera with 57 distinct species. Overall 39 % of the total
      morphotypes belonged to the Bacillus and Bacillus derived genera (BBDG) followed
      by Pseudomonas (14 %), Arthrobacter (9 %), Exiguobacterium (8 %), Alishewanella
      (4 %), Brachybacterium, Providencia, Planococcus (3 %), Janthinobacterium,
      Sphingobacterium, Kocuria (2 %) and Aurantimonas, Citricoccus,
      Cellulosimicrobium, Brevundimonas, Desemzia, Flavobacterium, Klebsiella,
      Paracoccus, Psychrobacter, Sporosarcina, Staphylococcus, Sinobaca,
      Stenotrophomonas, Sanguibacter, Vibrio (1 %). The representative isolates from
      each cluster were screened for their plant growth promoting characteristics at
      low temperature (5-15  degrees C). Variations were observed among strains for
      production of ammonia, hydrogen cyanide, indole-3-acetic acid and siderophore,
      solubilisation of phosphate, 1-aminocyclopropane-1-carboxylate deaminase activity
      and biocontrol activity against Rhizoctonia solani and Macrophomina phaseolina.
      Cold adapted microbes may have application as inoculants and biocontrol agents in
      crops growing at high altitudes under cold climate condition. 

PMID- 25371317
TI  - Atlas of care shows poor performance in treating diabetes in England.

PMID- 25371318
TI  - Non-alternant non-benzenoid aromatic compounds: past, present, and future.
AB  - The development of the chemistry of non-alternant non-benzenoid hydrocarbons is
      reviewed in connection with the International Symposium on Novel Aromatic
      Compounds (ISNA) and the author's personal anecdotes. Past molecules include the
      classics of this class of compounds, pentalene, azulene, and heptalene, and the
      structurally integrated congeners such as indacenes formed by benzannelation and
      benzinterposition, which were extensively studied during the last century.
      Indenofluorene isomers constructed by benzannelation to indacenes represent
      present molecules, which have attracted much interest in recent years in view of
      their potential in optoelectronic applications. The unusual properties of the
      most exotic isomer, indeno[2,1-b]fluorene, are specifically described to
      demonstrate that the benzannelation is not simply a modification for
      stabilization. Finally, as future molecules, those consisting of linear and
      cyclic arrays of indenofluorene motifs formed by further extension are proposed. 

PMID- 25371319
TI  - Endoscopic ultrasound-guided celiac ganglion radiofrequency ablation for pain
      control in pancreatic carcinoma.

PMID- 25371321
TI  - Silica-based ionogels: nanoconfined ionic liquid-rich fibers for headspace solid
      phase microextraction coupled with gas chromatography-barrier discharge
      ionization detection.
AB  - In this work, hybrid silica-based materials with immobilized ionic liquids (ILs)
      were prepared by sol-gel technology and evaluated as solid-phase microextraction
      (SPME) fiber coatings. High loadings of the IL 1-methyl-3-butylimidazolium
      bis(trifluoromethylsulfonyl)imide ([C4MIM][TFSI]) were confined within the hybrid
      network. Coatings composition and morphology were evaluated using scanning
      electron microscopy and energy dispersive X-ray spectrometry. The obtained
      ionogel SPME fibers exhibited high extractability for aromatic volatile
      compounds, yielding good sensitivity and precision when combined with a gas
      chromatograph with barrier ionization discharge (GC-BID) detection. A central
      composite design was used for assessing the effect of experimental parameters on
      the extraction process. Under optimized conditions, the proposed ionogel SPME
      fiber coatings enabled the achievement of excellent enrichment factors (up to
      7400). The limits of detection (LODs) were found in the range 0.03-1.27 MUg L(
      1), whereas the repeatability and fiber-to-fiber reproducibility were 5.6% and
      12.0% on average, respectively. Water samples were analyzed by the proposed
      methodology, showing recovery values in the range of 88.7-113.9%. The results
      obtained in this work suggest that ionogels can be promising coating materials
      for future applications of SPME and related sample preparation techniques. 

PMID- 25371320
TI  - Risk for ventricular fibrillation in peripartum cardiomyopathy with severely
      reduced left ventricular function-value of the wearable
      cardioverter/defibrillator.
AB  - AIMS: The true incidence of life-threatening ventricular tachyarrhythmic events
      and the risk of sudden cardiac death in the early stage of peripartum
      cardiomyopathy (PPCM) are still unknown. We aimed to assess the usefulness of the
      wearable cardioverter/defibrillator (WCD) to bridge a potential risk for life
      threatening arrhythmic events in patients with early PPCM, severely reduced left
      ventricular ejection fraction (LVEF) and symptoms of heart failure. METHODS AND
      RESULTS: Twelve consecutively admitted women with PPCM were included in this
      single-centre, prospective observational study between September 2012 and
      September 2013. Patients with LVEF <=35% were considered to use the WCD for 3
      months or even 6 months when considered necessary for LVEF recovery. Nine of the
      12 women had a severely reduced LVEF (mean 18.3%) at the time of study
      enrollment; seven women received a WCD, while two patients refused to wear a WCD.
      During a median WCD follow-up of 81 days (range 25-345 days), we observed a total
      of four events of ventricular fibrillation with appropriate and successful WCD
      shocks in three of the seven women receiving a WCD. No syncope or sudden
      arrhythmic deaths occurred in women not using the WCD during a median follow-up
      of 12 months (range 5-15 months). All women showed impressive improvement of LVEF
      during follow-up. CONCLUSION: PPCM patients with severely reduced LVEF have an
      elevated risk for ventricular tachyarrhythmias early after diagnosis. Therefore,
      use of the WCD should be considered in all women with early-stage PPCM and
      severely reduced LVEF during the first 6 months after initiation of heart failure
      therapy.

PMID- 25371322
TI  - Management and prevention of pertussis infection in neonates.
AB  - Despite the fact that universal immunization against pertussis led to a dramatic
      decrease in the incidence and mortality in high-income countries, it has left a
      window of vulnerability for newborns. Although specific guidelines concerning
      management of neonatal whooping cough have not yet been developed, the present
      review summarizes the main available recommendations on diagnostic work-up and
      treatment of neonatal pertussis. Additionally, new prevention strategies are
      explored, including the use of an additional booster dose of vaccine to
      adolescents and adults, vaccination of healthcare workers, immunization of
      household contacts and caregivers (cocooning strategy), vaccination of pregnant
      women and, finally, neonatal immunization with novel vaccines. These strategies
      are analyzed and discussed in terms of efficacy, safety and cost-effectiveness. 

PMID- 25371323
TI  - A phase I study of the histone deacetylase (HDAC) inhibitor entinostat, in
      combination with sorafenib in patients with advanced solid tumors.
AB  - Based on preclinical data demonstrating cytotoxic synergy between sorafenib and
      entinostat, a phase I study of this combination was conducted in patients with
      advanced solid tumors. Enrollment followed the traditional "3 + 3" dose
      escalation scheme. Entinostat was given orally once every 2 weeks, starting at a
      dose of 4 mg and escalating to 6 and 10 mg every 2 weeks. Sorafenib was
      administered as a continuous oral dose, escalating from 200 to 400 mg twice
      daily. A treatment cycle was 28 days. A total of 31 patients with advanced solid
      tumors were enrolled on the study. The three dose-limiting toxicities (DLTs)
      observed were grade 3 hand-foot syndrome, nausea/vomiting, and fatigue. MTD was
      not reached. The recommended phase II dose was defined as the full dose of the
      respective drugs administered individually. The most common grade 3-4 toxicities
      were muscle weakness (13 %), skin rash (10 %), fatigue (6 %), diarrhea (6 %), and
      hand-foot syndrome (3 %). One NSCLC patient achieved a partial response. Two
      patients (adenocarcinoma of GE junction and Hurthle cell carcinoma of the
      thyroid) were on the study for more than 9 months with stable disease. The
      combination of entinostat and sorafenib was well tolerated. Entinostat 10 mg
      orally once every 2 weeks in combination with sorafenib 400 mg orally twice
      daily, representing full single agent doses of each drug was identified as the
      recommended phase 2 dose (RP2D). These data support future clinical development
      of the combination of entinostat and sorafenib.

PMID- 25371324
TI  - Overexpression of adenylate cyclase-associated protein 1 may predict brain
      metastasis in non-small cell lung cancer.
AB  - This study was designed to establish a biomarker risk model for predicting brain
      metastasis (BM) in non-small cell lung cancer (NSCLC). The model comprises 120
      cases of NSCLC that were treated and followed up for 4 years. The patients were
      divided into the BM (n=50) and non-BM (other visceral metastasis and those
      without recurrence) (n=70) groups. Immunohistochemical and western blot analyses
      were performed in metastatic tissues of NSCLC. Multivariate regression analysis
      was performed to correlate the immunoreactive cyclase-associated protein 1 (CAP1)
      signal with BM. Survival analyses were performed by using the Kaplan-Meier
      method. CAP1 protein content and immunoreactivity were significantly increased in
      BM specimens compared to other-metastatic specimens. The survival analysis
      revealed that CAP1 overexpression was significantly associated with survival
      (P<0.05). The ROC test suggested that the area under the curve was 73.33%
      (P<0.001; 95% CI, 63.5-83.2%). When P=0.466, the sensitivity and specificity
      reached 79.5 and 67.1%, respectively. These findings suggested that CAP1 is
      involved in the BM of NSCLC, and that elevated levels of CAP1 expression may
      indicate a poor prognosis for patients with BM. The CAP1 molecular model may be
      useful in the prediction of the risk of BM in NSCLC.

PMID- 25371325
TI  - Presence of lymphatics in a rat tendon lesion model.
AB  - Tendons lack sufficient blood supply and represent a bradytroph tissue with
      prolonged healing time under pathological conditions. While the role of
      lymphatics in wound/defect healing in tissues with regular blood supply is well
      investigated, its involvement in tendon defects is not clear. We here try to
      identify the role of the lymphatic system in a tendon lesion model with
      morphological methods. A rat Achilles tendon lesion model (n = 5) was created via
      surgical intervention. Two weeks after surgery, animals were killed and lesioned
      site removed and prepared for polarization microscopy (picrosirius red) and
      immunohistochemistry using the lymphatic markers PROX1, VEGFR3, CCL21, LYVE-1,
      PDPN, and the vascular marker CD31. Additionally, DAPI was applied. Untreated
      tendons served as controls, confocal laser-scanning microscopy was used for
      documentation. At the lesion site, polarization microscopy revealed a structural
      reintegration while immunohistochemistry detected band-like profiles
      immunoreactive for PDPN, VEGFR3, CCL21, LYVE1, and CD31, surrounding DAPI
      positive nuclei. PROX1-positive nuclei were detected within the lesion forming
      lines and opposed to each other. These PROX1-positive nuclei were surrounded by
      LYVE-1- or VEGFR3-positive surfaces. Few CD31-positive profiles contained PROX1
      positive nuclei, while the majority of CD31-positive profiles lacked PROX1
      positive nuclei. VEGFR3-, PDPN-, and LYVE-1-positive profiles were numerous
      within the lesion site, but absent in control tissue. Within 2 weeks, a
      structural rearrangement takes place in this lesion model, with dense lymphatic
      supply. The role of lymphatics in tendon wound healing is unclear, and proposed
      model represents a good possibility to study healing dynamics and
      lymphangiogenesis in a tissue almost completely lacking lymphatics in
      physiological conditions.

PMID- 25371326
TI  - Vascular and neural stem cells in the gut: do they need each other?
AB  - Enteric neurons and blood vessels form intricate networks throughout the
      gastrointestinal tract. To support the hypothesis of a possible interaction of
      both networks, we investigated whether primary mesenteric vascular cells (MVCs)
      and enteric nervous system (ENS)-derived cells (ENSc) depend on each other using
      two- and three-dimensional in vitro assays. In a confrontation assay, both cell
      types migrated in a target-oriented manner towards each other. The migration of
      MVCs was significantly increased when cultured in ENSc-conditioned medium. Co
      cultures of ENSc with MVCs resulted in an improved ENSc proliferation and
      differentiation. Moreover, we analysed the formation of the vascular and nervous
      system in developing mice guts. It was found that the patterning of newly formed
      microvessels and neural stem cells, as confirmed by nestin and SOX2 stainings, is
      highly correlated in all parts of the developing gut. In particular in the distal
      colon, nestin/SOX2-positive cells were found in the tissues adjacent to the
      capillaries and in the capillaries themselves. Finally, in order to provide
      evidences for a mutual interaction between endothelial and neural cells, the
      vascular patterns of a RET((-/-)) knockout mouse model as well as human
      Hirschsprung's cases were analysed. In the distal colon of postnatal RET((-/-))
      knockout mice, the vascular and neural networks were similarly disrupted. In
      aganglionic zones of Hirschsprung's patients, the microvascular density was
      significantly increased compared with the ganglionic zone within the submucosa.
      Taken together, these findings indicate a strong interaction between the enteric
      nervous and vascular system. 

PMID- 25371327
TI  - Cellular and molecular characterization of a novel primary osteoblast culture
      from the vertebrate model organism Xenopus tropicalis.
AB  - Osteogenesis is the fundamental process by which bones are formed, maintained and
      regenerated. The osteoblasts deposit the bone mineralized matrix by secreting
      large amounts of extracellular proteins and by allowing the biochemical
      conditions for the nucleation of hydroxyapatite crystals. Normal bone formation
      requires a tight control of osteoblastic activity, and therefore, osteoblasts
      represent a major focus of interest in biomedical research. Several crucial
      features of osteogenesis can be readily recapitulated using murine, avian and
      fish primary and immortalized osteoblastic cultures. Here, we describe a novel
      and straightforward in vitro culture of primary osteoblasts from the amphibian
      Xenopus tropicalis, a major vertebrate model organism. X. tropicalis osteoblasts
      can readily be extracted from the frontoparietal bone of pre-metamorphosing
      tadpole skulls by series of gentle protease treatments. Such primary cultures
      efficiently proliferate and can conveniently be grown at room temperature, in the
      absence of CO2, on a variety of substrates. X. tropicalis primary osteoblasts
      express well-characterized genes known to be active during osteogenesis of
      teleost fish, chick, mouse and human. Upon differentiation, such cultures
      mineralize and activate DMP1, an osteocyte-specific gene. Importantly, X.
      tropicalis primary osteoblasts can be efficiently transfected and respond to the
      forced activation of the bone morphogenetic protein pathway by increasing their
      nuclear levels of phospho-Smad. Therefore, this novel primary culture is amenable
      to experimental manipulations and represents a valuable tool for improving our
      understanding of the complex network of molecular interactions that govern
      vertebrate bone formation. 

PMID- 25371328
TI  - Over-expression of muscle glycogen synthase in human diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is a major complication of diabetic patients and the
      leading cause of end-stage renal disease. Glomerular dysfunction plays a critical
      role in DN, but deterioration of renal function also correlates with tubular
      alterations. Human DN is characterized by glycogen accumulation in tubules.
      Although this pathological feature has long been recognized, little information
      exists about the triggering mechanism. In this study, we detected over-expression
      of muscle glycogen synthase (MGS) in diabetic human kidney. This enhanced
      expression suggests the participation of MGS in renal metabolic changes
      associated with diabetes. HK2 human renal cell line exhibited an intrinsic
      ability to synthesize glycogen, which was enhanced after over-expression of
      protein targeting to glycogen. A correlation between increased glycogen amount
      and cell death was observed. Based on a previous transcriptome study on human
      diabetic kidney disease, significant differences in the expression of genes
      involved in glycogen metabolism were analyzed. We propose that glucose, but not
      insulin, is the main modulator of MGS activity in HK2 cells, suggesting that
      blood glucose control is the best approach to modulate renal glycogen-induced
      damage during long-term diabetes.

PMID- 25371329
TI  - The function of gas vesicles in halophilic archaea and bacteria: theories and
      experimental evidence.
AB  - A few extremely halophilic Archaea (Halobacterium salinarum, Haloquadratum
      walsbyi, Haloferax mediterranei, Halorubrum vacuolatum, Halogeometricum
      borinquense, Haloplanus spp.) possess gas vesicles that bestow buoyancy on the
      cells. Gas vesicles are also produced by the anaerobic endospore-forming
      halophilic Bacteria Sporohalobacter lortetii and Orenia sivashensis. We have
      extensive information on the properties of gas vesicles in Hbt. salinarum and
      Hfx. mediterranei and the regulation of their formation. Different functions were
      suggested for gas vesicle synthesis: buoying cells towards oxygen-rich surface
      layers in hypersaline water bodies to prevent oxygen limitation, reaching higher
      light intensities for the light-driven proton pump bacteriorhodopsin, positioning
      the cells optimally for light absorption, light shielding, reducing the
      cytoplasmic volume leading to a higher surface-area-to-volume ratio (for the
      Archaea) and dispersal of endospores (for the anaerobic spore-forming Bacteria).
      Except for Hqr. walsbyi which abounds in saltern crystallizer brines, gas
      vacuolate halophiles are not among the dominant life forms in hypersaline
      environments. There only has been little research on gas vesicles in natural
      communities of halophilic microorganisms, and the few existing studies failed to
      provide clear evidence for their possible function. This paper summarizes the
      current status of the different theories why gas vesicles may provide a selective
      advantage to some halophilic microorganisms. 

PMID- 25371330
TI  - Pavilion lake microbialites: morphological, molecular and biochemical evidence
      for a cold-water transition to colonial aggregates.
AB  - The presence of microbialite structures in a freshwater, dimictic mid
      latitudelake and their establishment after the last ice age about 10,000 years
      ago is puzzling.Freshwater calcite microbialites at Pavilion Lake, British
      Columbia, Canada, consist of acomplex community of microorganisms that
      collectively form large, ordered structuredaggregates. This distinctive
      assemblage of freshwater calcite microbialites was studied through standard
      microbial methods, morphological observations, phospholipid fatty acid(PLFA)
      analysis, DNA sequencing and the identification of quorum sensing molecules.Our
      results suggest that the microbialites may represent a transitional form from
      theexclusively prokaryotic colonial precursors of stromatolites to the
      multicellular organismicaggregates that give rise to coral reefs. 

PMID- 25371331
TI  - Halophilic bacteria as a source of novel hydrolytic enzymes.
AB  - Hydrolases constitute a class of enzymes widely distributed in nature from
      bacteria to higher eukaryotes. The halotolerance of many enzymes derived from
      halophilic bacteria can be exploited wherever enzymatic transformations are
      required to function under physical and chemical conditions, such as in the
      presence of organic solvents and extremes in temperature and salt content. In
      recent years, different screening programs have been performed in saline habitats
      in order to isolate and characterize novel enzymatic activities with different
      properties to those of conventional enzymes. Several halophilic hydrolases have
      been described, including amylases, lipases and proteases, and then used for
      biotechnological applications. Moreover, the discovery of biopolymer-degrading
      enzymes offers a new solution for the treatment of oilfield waste, where high
      temperature and salinity are typically found, while providing valuable
      information about heterotrophic processes in saline environments. In this work,
      we describe the results obtained in different screening programs specially
      focused on the diversity of halophiles showing hydrolytic activities in saline
      and hypersaline habitats, including the description of enzymes with special
      biochemical properties. The intracellular lipolytic enzyme LipBL, produced by the
      moderately halophilic bacterium Marinobacter lipolyticus, showed advantages over
      other lipases, being an enzyme active over a wide range of pH values and
      temperatures. The immobilized LipBL derivatives obtained and tested in regio- and
      enantioselective reactions, showed an excellent behavior in the production of
      free polyunsaturated fatty acids (PUFAs). On the other hand, the extremely
      halophilic bacterium, Salicola marasensis sp. IC10 showing lipase and protease
      activities, was studied for its ability to produce promising enzymes in terms of
      its resistance to temperature and salinity. 

PMID- 25371332
TI  - Biohydrogen Production by the Thermophilic Bacterium Caldicellulosiruptor
      saccharolyticus: Current Status and Perspectives.
AB  - Caldicellulosiruptor saccharolyticus is one of the most thermophilic cellulolytic
      organisms known to date. This Gram-positive anaerobic bacterium ferments a broad
      spectrum of mono-, di- and polysaccharides to mainly acetate, CO2 and hydrogen.
      With hydrogen yields approaching the theoretical limit for dark fermentation of 4
      mol hydrogen per mol hexose, this organism has proven itself to be an excellent
      candidate for biological hydrogen production. This review provides an overview of
      the research on C. saccharolyticus with respect to the hydrolytic capability,
      sugar metabolism, hydrogen formation, mechanisms involved in hydrogen inhibition,
      and the regulation of the redox and carbon metabolism. Analysis of currently
      available fermentation data reveal decreased hydrogen yields under non-ideal
      cultivation conditions, which are mainly associated with the accumulation of
      hydrogen in the liquid phase. Thermodynamic considerations concerning the
      reactions involved in hydrogen formation are discussed with respect to the
      dissolved hydrogen concentration. Novel cultivation data demonstrate the
      sensitivity of C. saccharolyticus to increased hydrogen levels regarding
      substrate load and nitrogen limitation. In addition, special attention is given
      to the rhamnose metabolism, which represents an unusual type of redox balancing.
      Finally, several approaches are suggested to improve biohydrogen production by C.
      saccharolyticus. 

PMID- 25371334
TI  - A survey of protein structures from archaeal viruses.
AB  - Viruses that infect the third domain of life, Archaea, are a newly emerging field
      of interest. To date, all characterized archaeal viruses infect archaea that
      thrive in extreme conditions, such as halophilic, hyperthermophilic, and
      methanogenic environments. Viruses in general, especially those replicating in
      extreme environments, contain highly mosaic genomes with open reading frames
      (ORFs) whose sequences are often dissimilar to all other known ORFs. It has been
      estimated that approximately 85% of virally encoded ORFs do not match known
      sequences in the nucleic acid databases, and this percentage is even higher for
      archaeal viruses (typically 90%-100%). This statistic suggests that either virus
      genomes represent a larger segment of sequence space and/or that viruses encode
      genes of novel fold and/or function. Because the overall three-dimensional fold
      of a protein evolves more slowly than its sequence, efforts have been geared
      toward structural characterization of proteins encoded by archaeal viruses in
      order to gain insight into their potential functions. In this short review, we
      provide multiple examples where structural characterization of archaeal viral
      proteins has indeed provided significant functional and evolutionary insight. 

PMID- 25371333
TI  - Surface appendages of archaea: structure, function, genetics and assembly.
AB  - Organisms representing diverse subgroupings of the Domain Archaea are known to
      possess unusual surface structures. These can include ones unique to Archaea such
      as cannulae and hami as well as archaella (archaeal flagella) and various types
      of pili that superficially resemble their namesakes in Bacteria, although with
      significant differences. Major advances have occurred particularly in the study
      of archaella and pili using model organisms with recently developed advanced
      genetic tools. There is common use of a type IV pili-model of assembly for
      several archaeal surface structures including archaella, certain pili and sugar
      binding structures termed bindosomes. In addition, there are widespread
      posttranslational modifications of archaellins and pilins with N-linked glycans,
      with some containing novel sugars. Archaeal surface structures are involved in
      such diverse functions as swimming, attachment to surfaces, cell to cell contact
      resulting in genetic transfer, biofilm formation, and possible intercellular
      communication. Sometimes functions are co-dependent on other surface structures.
      These structures and the regulation of their assembly are important features that
      allow various Archaea, including thermoacidophilic, hyperthermophilic,
      halophilic, and anaerobic ones, to survive and thrive in the extreme environments
      that are commonly inhabited by members of this domain. 

PMID- 25371335
TI  - Quorum sensing in extreme environments.
AB  - Microbial communication, particularly that of quorum sensing, plays an important
      role in regulating gene expression in a range of organisms. Although this
      phenomenon has been well studied in relation to, for example, virulence gene
      regulation, the focus of this article is to review our understanding of the role
      of microbial communication in extreme environments. Cell signaling regulates many
      important microbial processes and may play a pivotal role in driving microbial
      functional diversity and ultimately ecosystem function in extreme environments.
      Several recent studies have characterized cell signaling in modern analogs to
      early Earth communities (microbial mats), and characterization of cell signaling
      systems in these communities may provide unique insights in understanding the
      microbial interactions involved in function and survival in extreme environments.
      Cell signaling is a fundamental process that may have co-evolved with communities
      and environmental conditions on the early Earth. Without cell signaling,
      evolutionary pressures may have even resulted in the extinction rather than
      evolution of certain microbial groups. One of the biggest challenges in
      extremophile biology is understanding how and why some microbial functional
      groups are located where logically they would not be expected to survive, and
      tightly regulated communication may be key. Finally, quorum sensing has been
      recently identified for the first time in archaea, and thus communication at
      multiple levels (potentially even inter-domain) may be fundamental in extreme
      environments. 

PMID- 25371336
TI  - Periplasmic Binding Proteins in Thermophiles: Characterization and Potential
      Application of an Arginine-Binding Protein from Thermotoga maritima: A Brief
      Thermo-Story.
AB  - Arginine-binding protein from the extremophile Thermotoga maritima is a 27.7 kDa
      protein possessing the typical two-domain structure of the periplasmic binding
      proteins family. The protein is characterized by a very high specificity and
      affinity to bind to arginine, also at high temperatures. Due to its features,
      this protein could be taken into account as a potential candidate for the design
      of a biosensor for arginine. It is important to investigate the stability of
      proteins when they are used for biotechnological applications. In this article,
      we review the structural and functional features of an arginine-binding protein
      from the extremophile Thermotoga maritima with a particular eye on its potential
      biotechnological applications. 

PMID- 25371337
TI  - Predator avoidance in extremophile fish.
AB  - Extreme habitats are often characterized by reduced predation pressures, thus
      representing refuges for the inhabiting species. The present study was designed
      to investigate predator avoidance of extremophile populations of Poecilia
      mexicana and P. sulphuraria that either live in hydrogen sulfide-rich (sulfidic)
      springs or cave habitats, both of which are known to have impoverished piscine
      predator regimes. Focal fishes that inhabited sulfidic springs showed slightly
      weaker avoidance reactions when presented with several naturally occurring
      predatory cichlids, but strongest differences to populations from non-sulfidic
      habitats were found in a decreased shoaling tendency with non-predatory swordtail
      (Xiphophorus hellerii) females. When comparing avoidance reactions between P.
      mexicana from a sulfidic cave (Cueva del Azufre) and the adjacent sulfidic
      surface creek (El Azufre), we found only slight differences in predator
      avoidance, but surface fish reacted much more strongly to the non-predatory
      cichlid Vieja bifasciata. Our third experiment was designed to disentangle
      learned from innate effects of predator recognition. We compared laboratory
      reared (i.e., predator-naive) and wild-caught (i.e., predator-experienced)
      individuals of P. mexicana from a non-sulfidic river and found no differences in
      their reaction towards the presented predators. Overall, our results indicate (1)
      that predator avoidance is still functional in extremophile Poecilia spp. and (2)
      that predator recognition and avoidance reactions have a strong genetic basis. 

PMID- 25371338
TI  - Pivotal Enzyme in Glutamate Metabolism of Poly-g-Glutamate-Producing Microbes.
AB  - The extremely halophilic archaeon Natrialba aegyptiaca secretes the L-homo type
      of poly-g-glutamate (PGA) as an extremolyte. We examined the enzymes involved in
      glutamate metabolism and verified the presence of L-glutamate dehydrogenases, L
      aspartate aminotransferase, and L-glutamate synthase. However, neither glutamate
      racemase nor D-amino acid aminotransferase activity was detected, suggesting the
      absence of sources of D-glutamate. In contrast, D-glutamate-rich PGA producers
      mostly possess such intracellular sources of D-glutamate. The results of our
      present study indicate that the D-glutamate-anabolic enzyme "glutamate racemase"
      is pivotal in the biosynthesis of PGA. 

PMID- 25371339
TI  - Evolution of microbial "streamer" growths in an acidic, metal-contaminated stream
      draining an abandoned underground copper mine.
AB  - A nine year study was carried out on the evolution of macroscopic "acid streamer"
      growths in acidic, metal-rich mine water from the point of construction of a new
      channel to drain an abandoned underground copper mine. The new channel became
      rapidly colonized by acidophilic bacteria: two species of autotrophic iron
      oxidizers (Acidithiobacillus ferrivorans and "Ferrovum myxofaciens") and a
      heterotrophic iron-oxidizer (a novel genus/species with the proposed name
      "Acidithrix ferrooxidans"). The same bacteria dominated the acid streamer
      communities for the entire nine year period, with the autotrophic species
      accounting for ~80% of the micro-organisms in the streamer growths (as determined
      by terminal restriction enzyme fragment length polymorphism (T-RFLP) analysis).
      Biodiversity of the acid streamers became somewhat greater in time, and included
      species of heterotrophic acidophiles that reduce ferric iron (Acidiphilium,
      Acidobacterium, Acidocella and gammaproteobacterium WJ2) and other autotrophic
      iron-oxidizers (Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans).
      The diversity of archaea in the acid streamers was far more limited; relatively
      few clones were obtained, all of which were very distantly related to known
      species of euryarchaeotes. Some differences were apparent between the acid
      streamer community and planktonic-phase bacteria. This study has provided unique
      insights into the evolution of an extremophilic microbial community, and
      identified several novel species of acidophilic prokaryotes. 

PMID- 25371340
TI  - A Laboratory of Extremophiles: Iceland Coordination Action for Research
      Activities on Life in Extreme Environments (CAREX) Field Campaign.
AB  - Existence of life in extreme environments has been known for a long time, and
      their habitants have been investigated by different scientific disciplines for
      decades. However, reports of multidisciplinary research are uncommon. In this
      paper, we report an interdisciplinary three-day field campaign conducted in the
      framework of the Coordination Action for Research Activities on Life in Extreme
      Environments (CAREX) FP7EU program, with participation of experts in the fields
      of life and earth sciences. In situ experiments and sampling were performed in a
      20 m long hot springs system of different temperature (57  degrees C to 100 
      degrees C) and pH (2 to 4). Abiotic factors were measured to study their
      influence on the diversity. The CO2 and H2S concentration varied at different
      sampling locations in the system, but the SO2 remained the same. Four biofilms,
      mainly composed by four different algae and phototrophic protists, showed
      differences in photosynthetic activity. Varying temperature of the sampling
      location affects chlorophyll fluorescence, not only in the microbial mats, but
      plants (Juncus), indicating selective adaptation to the environmental conditions.
      Quantitative polymerase chain reaction (PCR), DNA microarray and denaturing
      gradient gel electrophoresis (DGGE)-based analysis in laboratory showed the
      presence of a diverse microbial population. Even a short duration (30 h)
      deployment of a micro colonizer in this hot spring system led to colonization of
      microorganisms based on ribosomal intergenic spacer (RISA) analysis. Polyphasic
      analysis of this hot spring system was possible due to the involvement of
      multidisciplinary approaches. 

PMID- 25371341
TI  - Molecular Mechanisms of Adaptation of the Moderately Halophilic Bacterium
      Halobacillis halophilus to Its Environment.
AB  - The capability of osmoadaptation is a prerequisite of organisms that live in an
      environment with changing salinities. Halobacillus halophilus is a moderately
      halophilic bacterium that grows between 0.4 and 3 M NaCl by accumulating both
      chloride and compatible solutes as osmolytes. Chloride is absolutely essential
      for growth and, moreover, was shown to modulate gene expression and activity of
      enzymes involved in osmoadaptation. The synthesis of different compatible solutes
      is strictly salinity- and growth phase-dependent. This unique hybrid strategy of
      H. halophilus will be reviewed here taking into account the recently published
      genome sequence. Based on identified genes we will speculate about possible
      scenarios of the synthesis of compatible solutes and the uptake of potassium ion
      which would complete our knowledge of the fine-tuned osmoregulation and
      intracellular osmolyte balance in H. halophilus. 

PMID- 25371342
TI  - Properties of Halococcus salifodinae, an Isolate from Permian Rock Salt Deposits,
      Compared with Halococci from Surface Waters.
AB  - Halococcus salifodinae BIpT DSM 8989T, an extremely halophilic archaeal isolate
      from an Austrian salt deposit (Bad Ischl), whose origin was dated to the Permian
      period, was described in 1994. Subsequently, several strains of the species have
      been isolated, some from similar but geographically separated salt deposits. Hcc.
      salifodinae may be regarded as one of the most ancient culturable species which
      existed already about 250 million years ago. Since its habitat probably did not
      change during this long period, its properties were presumably not subjected to
      the needs of mutational adaptation. Hcc. salifodinae and other isolates from
      ancient deposits would be suitable candidates for testing hypotheses on
      prokaryotic evolution, such as the molecular clock concept, or the net-like
      history of genome evolution. A comparison of available taxonomic characteristics
      from strains of Hcc. salifodinae and other Halococcus species, most of them
      originating from surface waters, is presented. The cell wall polymer of Hcc.
      salifodinae was examined and found to be a heteropolysaccharide, similar to that
      of Hcc. morrhuae. Polyhydroxyalkanoate granules were present in Hcc. salifodinae,
      suggesting a possible lateral gene transfer before Permian times. 

PMID- 25371344
TI  - Microorganism response to stressed terrestrial environments: a Raman
      spectroscopic perspective of extremophilic life strategies.
AB  - Raman spectroscopy is a valuable analytical technique for the identification of
      biomolecules and minerals in natural samples, which involves little or minimal
      sample manipulation. In this paper, we evaluate the advantages and disadvantages
      of this technique applied to the study of extremophiles. Furthermore, we provide
      a review of the results published, up to the present point in time, of the bio-
      and geo-strategies adopted by different types of extremophile colonies of
      microorganisms. We also show the characteristic Raman signatures for the
      identification of pigments and minerals, which appear in those complex samples. 

PMID- 25371343
TI  - Quorum sensing in some representative species of halomonadaceae.
AB  - Cell-to-cell communication, or quorum-sensing (QS), systems are employed by
      bacteria for promoting collective behaviour within a population. An analysis to
      detect QS signal molecules in 43 species of the Halomonadaceae family revealed
      that they produced N-acyl homoserine lactones (AHLs), which suggests that the QS
      system is widespread throughout this group of bacteria. Thin-layer chromatography
      (TLC) analysis of crude AHL extracts, using Agrobacterium tumefaciens NTL4
      (pZLR4) as biosensor strain, resulted in different profiles, which were not
      related to the various habitats of the species in question. To confirm AHL
      production in the Halomonadaceae species, PCR and DNA sequencing approaches were
      used to study the distribution of the luxI-type synthase gene. Phylogenetic
      analysis using sequence data revealed that 29 of the species studied contained a
      LuxI homolog. Phylogenetic analysis showed that sequences from Halomonadaceae
      species grouped together and were distinct from other members of the
      Gammaproteobacteria and also from species belonging to the Alphaproteobacteria
      and Betaproteobacteria. 

PMID- 25371345
TI  - "We Hide Under the Scriptures": Conceptualization of Health Among United
      Methodist Church Clergy in Kenya.
AB  - As community leaders, clergy are well-positioned to impact the health of their
      congregants. Clergy's conceptualizations of health influence their own self-care
      and how they minister to others. Interviews and focus group discussions on health
      conceptualizations and health-seeking behaviors were conducted with 49 United
      Methodist Church clergy in Western Kenya. Data were analyzed using interpretative
      phenomenological methods. Participants defined health holistically using an
      environmental health model. Some participants reported not seeking health care so
      their congregants would believe that their faith kept them healthy. Participants
      who believed that health comes directly from God reported seeking health care
      less often. Participants also reported combining traditional indigenous medicine
      with Western medicine. This study has implications for health promotion among
      Kenyan clergy and offers the first study of health conceptualization among clergy
      in Africa. 

PMID- 25371346
TI  - Good Practice Chaplaincy: An Exploratory Study Identifying the Appropriate
      Skills, Attitudes and Practices for the Selection, Training and Utilisation of
      Chaplains.
AB  - This article presents an overview of exploratory research regarding the skills,
      knowledge, attitudes and practices considered necessary for chaplains to be
      highly competent in providing holistic care to clients and staff. Utilising a
      qualitative methodology, two focus groups comprising Salvation Army chaplains and
      their managers provided data about their expectations of chaplaincy personnel and
      about the pastoral care interventions undertaken by chaplains. The results
      indicated that while there were some differences in opinion, nevertheless, in
      overall terms, there was general agreement between chaplains and their managers
      about particular personal and professional qualities necessary for chaplains to
      be considered appropriate and proficient. Evidence was also obtained indicating a
      need for change with regard to the organisational attitude and culture of The
      Salvation Army towards chaplaincy. Recommendations are presented concerning (1)
      the selection criteria for chaplaincy, (2) training and utilisation of chaplains
      plus (3) issues relating to organizational cultural change necessary to develop a
      future-ready chaplaincy more suitable for the twenty-first century. 

PMID- 25371347
TI  - Does the availability of therapeutic drug monitoring, computerised dose
      recommendation and prescribing decision support services promote compliance with
      national gentamicin prescribing guidelines?
AB  - BACKGROUND: Gentamicin is an aminoglycoside antibiotic that is highly effective
      in treating Gram-negative infections, but inappropriate use leads to toxicity. In
      2010, the Australian Therapeutic Guidelines (Antibiotic) were revised to
      recommend the use of computerised methods to individualise dosing of gentamicin
      and optimise therapy, rather than traditional nomogram approaches. AIM: To
      determine whether gentamicin prescribing was compliant with the Australian
      Therapeutic Guidelines, version 14 (2010) in a setting where computerised dose
      recommendation resources and computerised decision support were available, and to
      determine why the resources were effective or ineffective in achieving compliance
      to guidelines. METHODS: During phase 1, a retrospective audit of gentamicin
      prescribing from 1 January 2012 to 31 December 2012 (n = 826) at a 320-bed
      teaching hospital in Sydney was undertaken. In phase 2, 12 doctors from
      specialties with high-volume prescribing of gentamicin were interviewed. RESULTS:
      Intravenous gentamicin was used in 545 cases, 81% of which were for short-term
      therapy (<=48 h). Doctors feared inducing toxicity in patients, but limited the
      dose rather than altering the dosing interval according to renal function. Of the
      'continued' dosing cases, 55% went unmonitored and the computerised dose
      recommendation service was rarely used. Doctors were unaware of its availability
      despite electronic alerts accompanying prescriptions of gentamicin. CONCLUSIONS:
      In comparison with the national guidelines, there was significant under-dosing
      and monitoring practices were haphazard. Computerised electronic alerts were
      ineffective in informing users. To improve prescribing practices, we recommend
      exploring alternative computerised decision support approaches (e.g. pre-written
      orders) and more pervasive and persuasive implementation strategies.

PMID- 25371348
TI  - Facet dependent SEI formation on the LiNi(0.5)Mn(1.5)O4 cathode identified by in
      situ single particle atomic force microscopy.
AB  - A facile protocol is developed for the direct observation and characterization of
      a single particle electrode during the lithium ion battery operation by using in
      situ AFM. The SEI formation on the LiNi0.5Mn1.5O4 particle cathode surface is
      found to be highly related to the exposed planes. 

PMID- 25371349
TI  - Commentary on King W, Ahmed S, Baisden J, Patel N, MacVicar J, Kennedy DJ.
      Diagnosis of posterior sacroiliac complex pain: a systematic review with
      comprehensive analysis of the published data.

PMID- 25371350
TI  - Orexin excites rat inferior vestibular nuclear neurons via co-activation of OX1
      and OX 2 receptors.
AB  - Orexin deficiency results in cataplexy, a motor deficit characterized by sudden
      loss of muscle tone, strongly indicating an active role of central orexinergic
      system in motor control. However, effects of orexin on neurons in central motor
      structures are still largely unknown. Our previous studies have revealed that
      orexin excites neurons in the cerebellar nuclei and lateral vestibular nucleus,
      two important subcortical motor centers for control of muscle tone. Here, we
      report that both orexin-A and orexin-B depolarizes and increases the firing rate
      of neurons in the inferior vestibular nucleus (IVN), the largest nucleus in the
      vestibular nuclear complex and holding an important position in integration of
      information signals in the control of body posture. TTX does not block orexin
      induced excitation on IVN neurons, suggesting a direct postsynaptic action of the
      neuropeptide. Furthermore, bath application of orexin induces an inward current
      on IVN neurons in a concentration-dependent manner. SB334867 and TCS-OX2-29,
      specific OX1 and OX2 receptor antagonists, blocked the excitatory effect of
      orexin, and [Ala(11), D-Leu(15)]-orexin B, a selective OX2 receptor agonist,
      mimics the orexin-induced inward current on IVN neurons. qPCR and
      immunofluorescence results show that both OX1 and OX2 receptor mRNAs and proteins
      are expressed and localized in the rat IVN. These results demonstrate that orexin
      excites the IVN neurons by co-activation of both OX1 and OX2 receptors,
      suggesting that via the direct modulation on the IVN, the central orexinergic
      system may actively participate in the central vestibular-mediated postural and
      motor control. 

PMID- 25371353
TI  - Influence of cadmium and mycorrhizal fungi on the fatty acid profile of flax
      (Linum usitatissimum) seeds.
AB  - BACKGROUND: The soil environment can affect not only the quantity of crops
      produced but also their nutritional quality. We examined the combined effects of
      below-ground cadmium (0, 5, and 15 ppm) and mycorrhizal fungi (presence and
      absence) on the concentration of five major fatty acids within flax seeds (Linum
      usitatissimum). RESULTS: Plants grown with mycorrhizal fungi produced seeds that
      contained higher concentrations of unsaturated (18:1, 18:2 and 18:3), but not
      saturated (16:0 and 18:0) fatty acids. The effects of mycorrhizal fungi on the
      concentration of unsaturated fatty acids in seeds were most pronounced when plant
      roots were exposed to 15 ppm Cd (i.e. the concentrations of 18:1, 18:2 and 18:3
      increased by 169%, 370% and 150%, respectively). CONCLUSIONS: The pronounced
      effects of mycorrhizal fungi on the concentration of unsaturated fatty acids at
      15 ppm Cd may have been due to the presence of elevated levels of Cd within
      seeds. Our results suggest that, once the concentration of cadmium within seeds
      reaches a certain threshold, this heavy metal may improve the efficiency of
      enzymes that convert saturated fatty acids to unsaturated fatty acids.

PMID- 25371351
TI  - Different doses of micafungin for prophylaxis of invasive fungal diseases in
      hemato-oncological high-risk patients: a web-based non-interventional trial in
      four large university hospitals in Germany.
AB  - INTRODUCTION: Treatment indications of new antifungals in clinical practice often
      deviate from the strict criteria used in controlled clinical trials. Under
      routine clinical conditions, beneficial and adverse effects, not previously
      described in clinical trials may be observed. The aim of this study was to
      describe customary prescription and treatment strategies of micafungin (MCFG).
      METHODS: A registry was set up on www.ClinicalSurveys.net and physicians were
      invited to provide retrospective information on cases they had treated with MCFG.
      Documentation comprised demographic information, underlying disease,
      effectiveness, safety, and tolerability of MCFG. RESULTS: A total of 125 episodes
      of patients hospitalized between September 2009 and February 2012 were
      documented, of which 7 had to be excluded because of incomplete documentation.
      The most common risk factors of patients were hematological malignancy (n = 116,
      98.3%) and antibiotic treatment >3 days (n = 115, 97.5%). MCFG was administered
      as prophylaxis in 106 (89.9%) patients. Median duration of MCFG application as
      prophylaxis was 21 days (range: 3-78); 53 of the patients (50%) received a dose
      of 50 mg, while the other 53 (50%) received 100 mg/day. For the different doses,
      prophylactic outcome was rated as success in 42 (79.2%) vs. 52 (98.1%; P = 0.004)
      patients. Fifty-five patients (51.9%) were treated with posaconazole before
      initiation of MCFG. Four patients (7.5%) developed a proven invasive fungal
      disease (IFD) while being treated with 50 mg MCFG, compared to no patient treated
      with 100 mg (P = 0.118). At the end of MCFG prophylaxis, 24 (22.6%) patients were
      switched to fluconazole and 64 (60.3%) patients to posaconazole. CONCLUSION: Our
      study shows clinical effectiveness of MCFG prophylaxis with low rates of
      breakthrough fungal infections. In most cases, MCFG was part of a multi-modal
      antifungal prophylactic strategy. Investigators reported fewer proven IFDs in
      patients receiving therapeutic doses of MCFG as prophylaxis.

PMID- 25371354
TI  - Concordance of hypervascular liver nodule characterization between the organ
      procurement and transplant network and liver imaging reporting and data system
      classifications.
AB  - PURPOSE: To determine the rate of agreement between the Organ Procurement and
      Transplant Network (OPTN) and Liver Imaging Reporting and Data System (LI-RADS)
      classifications for hypervascular liver nodules at least 1 cm in diameter, and
      for patient eligibility for hepatocellular/MELD (Model for Endstage Liver
      Disease) exception points. MATERIALS AND METHODS: This retrospective study was
      approved by our Institutional Review Board and was compliant with the Health
      Insurance Portability and Accountability Act. The requirement for informed
      consent was waived. This study included 200 hypervascular hepatocellular nodules
      at least 1 cm in diameter on computed tomography (CT) or magnetic resonance
      imaging (MRI) examinations in 105 patients with chronic liver disease. Three
      radiologists blinded to clinical data independently evaluated nodule
      characteristics, including washout, capsule, size, and size on prior examination.
      Based on those characteristics, nodules were automatically classified as definite
      hepatocellular carcinoma (HCC) or not definite HCC using both the OPTN and LI
      RADS classifications. Using these classifications and the Milan criteria, each
      examination was determined to be "below transplant criteria," "within transplant
      criteria," or "beyond transplant criteria." Agreement was assessed between
      readers and classification systems, using Fleiss' kappa, intraclass correlation
      coefficients (ICCs), and simple proportions. RESULTS: Interreader agreement was
      moderate for nodule features (kappa = 0.59-0.69) and nodule classification (0.66
      0.69). The two systems were in nearly complete agreement on nodule category
      assignment (98.7% [592/600]) and patient eligibility for transplant exemption
      priority (99.4% [313/315]). A few discrepancies occurred for the nodule feature
      of growth (1.3% [8/600]) and for nodule category assignment (1.3% [8/600]).
      CONCLUSION: Agreement between the OPTN and LI-RADS classifications is very strong
      for categorization of hypervascular liver nodules at least 1 cm in diameter, and
      for patient eligibility for hepatocellular/MELD exception points. Interreader
      variability is much higher than intersystem variability.

PMID- 25371355
TI  - Paediatric prescribing: why children are not small adults.

PMID- 25371356
TI  - Degradation and toxicity assessment of the nonionic surfactant TritonTM X-45 by
      the peroxymonosulfate/UV-C process.
AB  - The degradation and mineralization of the nonionic surfactant octylphenol
      ethoxylate (OPEO), commercially known as TritonTM X-45, by the peroxymonosulfate
      (PMS)/UV-C process were investigated. Three different toxicity tests (Daphnia
      magna, Vibrio fischeri and Pseudokirchneriella subcapitata) as well as the Yeast
      Estrogen Screen (YES) bioassay were undertaken to evaluate the potential toxic
      and estrogenic effects of OPEO and its oxidation products. OPEO removal was very
      fast and complete after 7 min via PMS/UV-C treatment under the investigated
      reaction conditions (OPEO = 20 mg L(-1) (47 MUM); TOC = 12 mg L(-1); PMS = 2.5
      mM; initial reaction pH = 6.5; applied UV-C dose = 21 Wh L(-1)). TOC removal also
      proceeded rapidly; a gradual decrease was observed resulting in an overall TOC
      removal of 84%. The toxic responses of PMS/UV-C treated OPEO solutions varied
      according to the test organism used in the bioassay. Daphnia magna was found to
      be most sensitive to aqueous OPEO, whereas Pseudokirchneriella subcapitata
      appeared to be the least sensitive one. Daphnia magna and Vibrio fischeri tests
      revealed that the inhibitory effect of OPEO decreased significantly during the
      course of treatment. On the other hand, PMS/UV-C oxidation products exhibited a
      high toxic effect towards Pseudokirchneriella subcapitata (around 60%). YES test
      results underlined the need for improving the PMS/UV-C treatment performance to
      remove the estrogenic activity of OPEO and its oxidation products. 

PMID- 25371357
TI  - Chemokine signaling in development and disease.
AB  - Chemokines are a group of small, secreted molecules that signal through G protein
      coupled receptors to promote cell survival and proliferation and to provide
      directional guidance to migrating cells. CXCL12 is one of the most evolutionary
      conserved chemokines and signals through the chemokine receptor CXCR4 to guide
      cell migration during embryogenesis, immune cell trafficking and cancer
      metastasis. Here and in the accompanying poster, we provide an overview of
      chemokine signaling, focusing on CXCL12, and we highlight some of the different
      chemokine-dependent strategies used to guide migrating cells.

PMID- 25371359
TI  - Leaf development and morphogenesis.
AB  - The development of plant leaves follows a common basic program that is flexible
      and is adjusted according to species, developmental stage and environmental
      circumstances. Leaves initiate from the flanks of the shoot apical meristem and
      develop into flat structures of variable sizes and forms. This process is
      regulated by plant hormones, transcriptional regulators and mechanical properties
      of the tissue. Here, we review recent advances in the understanding of how these
      factors modulate leaf development to yield a substantial diversity of leaf forms.
      We discuss these issues in the context of leaf initiation, the balance between
      morphogenesis and differentiation, and patterning of the leaf margin.

PMID- 25371358
TI  - Stem cells and the impact of ROS signaling.
AB  - An appropriate balance between self-renewal and differentiation is crucial for
      stem cell function during both early development and tissue homeostasis
      throughout life. Recent evidence from both pluripotent embryonic and adult stem
      cell studies suggests that this balance is partly regulated by reactive oxygen
      species (ROS), which, in synchrony with metabolism, mediate the cellular redox
      state. In this Primer, we summarize what ROS are and how they are generated in
      the cell, as well as their downstream molecular targets. We then review recent
      findings that provide molecular insights into how ROS signaling can influence
      stem cell homeostasis and lineage commitment, and discuss the implications of
      this for reprogramming and stem cell ageing. We conclude that ROS signaling is an
      emerging key regulator of multiple stem cell populations.

PMID- 25371360
TI  - Symmetry breaking, germ layer specification and axial organisation in aggregates
      of mouse embryonic stem cells.
AB  - Mouse embryonic stem cells (mESCs) are clonal populations derived from
      preimplantation mouse embryos that can be propagated in vitro and, when placed
      into blastocysts, contribute to all tissues of the embryo and integrate into the
      normal morphogenetic processes, i.e. they are pluripotent. However, although they
      can be steered to differentiate in vitro into all cell types of the organism,
      they cannot organise themselves into structures that resemble embryos. When
      aggregated into embryoid bodies they develop disorganised masses of different
      cell types with little spatial coherence. An exception to this rule is the
      emergence of retinas and anterior cortex-like structures under minimal culture
      conditions. These structures emerge from the cultures without any axial
      organisation. Here, we report that small aggregates of mESCs, of about 300 cells,
      self-organise into polarised structures that exhibit collective behaviours
      reminiscent of those that cells exhibit in early mouse embryos, including
      symmetry breaking, axial organisation, germ layer specification and cell
      behaviour, as well as axis elongation. The responses are signal specific and
      uncouple processes that in the embryo are tightly associated, such as
      specification of the anteroposterior axis and anterior neural development, or
      endoderm specification and axial elongation. We discuss the meaning and
      implications of these observations and the potential uses of these structures
      which, because of their behaviour, we suggest to call 'gastruloids'.

PMID- 25371361
TI  - Wnt/beta-catenin and FGF signalling direct the specification and maintenance of a
      neuromesodermal axial progenitor in ensembles of mouse embryonic stem cells.
AB  - The development of the central nervous system is known to result from two
      sequential events. First, an inductive event of the mesoderm on the overlying
      ectoderm that generates a neural plate that, after rolling into a neural tube,
      acts as the main source of neural progenitors. Second, the axial regionalization
      of the neural plate that will result in the specification of neurons with
      different anteroposterior identities. Although this description of the process
      applies with ease to amphibians and fish, it is more difficult to confirm in
      amniote embryos. Here, a specialized population of cells emerges at the end of
      gastrulation that, under the influence of Wnt and FGF signalling, expands and
      generates the spinal cord and the paraxial mesoderm. This population is known as
      the long-term neuromesodermal precursor (NMp). Here, we show that controlled
      increases of Wnt/beta-catenin and FGF signalling during adherent culture
      differentiation of mouse embryonic stem cells (mESCs) generates a population with
      many of the properties of the NMp. A single-cell analysis of gene expression
      within this population reveals signatures that are characteristic of stem cell
      populations. Furthermore, when this activation is triggered in three-dimensional
      aggregates of mESCs, the population self-organizes macroscopically and undergoes
      growth and axial elongation that mimics some of the features of the embryonic
      spinal cord and paraxial mesoderm. We use both adherent and three-dimensional
      cultures of mESCs to probe the establishment and maintenance of NMps and their
      differentiation.

PMID- 25371362
TI  - SOX9 accelerates ESC differentiation to three germ layer lineages by repressing
      SOX2 expression through P21 (WAF1/CIP1).
AB  - Upon removal of culture conditions that maintain an undifferentiated state, mouse
      embryonic stem cells (ESCs) differentiate into various cell types.
      Differentiation can be facilitated by forced expression of certain transcription
      factors (TFs), each of which can generally specify a particular developmental
      lineage. We previously established 137 mouse ESC lines, each of which carried a
      doxycycline-controllable TF. Among them, Sox9 has unique capacity: its forced
      expression accelerates differentiation of mouse ESCs into cells of all three germ
      layers. With the additional use of specific culture conditions, overexpression of
      Sox9 facilitated the generation of endothelial cells, hepatocytes and neurons
      from ESCs. Furthermore, Sox9 action increases formation of p21 (WAF1/CIP1), which
      then binds to the SRR2 enhancer of pluripotency marker Sox2 and inhibits its
      expression. Knockdown of p21 abolishes inhibition of Sox2 and Sox9-accelerated
      differentiation, and reduction of Sox2 2 days after the beginning of ESC
      differentiation can comparably accelerate mouse ESC formation of cells of three
      germ layers. These data implicate the involvement of the p21-Sox2 pathway in the
      mechanism of accelerated ESC differentiation by Sox9 overexpression. The
      molecular cascade could be among the first steps to program ESC differentiation.

PMID- 25371363
TI  - A non-cell-autonomous role for Ras signaling in C. elegans neuroblast
      delamination.
AB  - Receptor tyrosine kinase (RTK) signaling through Ras influences many aspects of
      normal cell behavior, including epithelial-to-mesenchymal transition, and
      aberrant signaling promotes both tumorigenesis and metastasis. Although many such
      effects are cell-autonomous, here we show a non-cell-autonomous role for RTK-Ras
      signaling in the delamination of a neuroblast from an epithelial organ. The C.
      elegans renal-like excretory organ is initially composed of three unicellular
      epithelial tubes, namely the canal, duct and G1 pore cells; however, the G1 cell
      later delaminates from the excretory system to become a neuroblast and is
      replaced by the G2 cell. G1 delamination and G2 intercalation involve
      cytoskeletal remodeling, interconversion of autocellular and intercellular
      junctions and migration over a luminal extracellular matrix, followed by G1
      junction loss. LET-23/EGFR and SOS-1, an exchange factor for Ras, are required
      for G1 junction loss but not for initial cytoskeletal or junction remodeling.
      Surprisingly, expression of activated LET-60/Ras in the neighboring duct cell,
      but not in the G1 or G2 cells, is sufficient to rescue sos-1 delamination
      defects, revealing that Ras acts non-cell-autonomously to permit G1 delamination.
      We suggest that, similarly, oncogenic mutations in cells within a tumor might
      help create a microenvironment that is permissive for other cells to detach and
      ultimately metastasize.

PMID- 25371365
TI  - Class I KNOX transcription factors promote differentiation of cambial derivatives
      into xylem fibers in the Arabidopsis hypocotyl.
AB  - The class I KNOX transcription factors SHOOT MERISTEMLESS (STM) and KNAT1 are
      important regulators of meristem maintenance in shoot apices, with a dual role of
      promoting cell proliferation and inhibiting differentiation. We examined whether
      they control stem cell maintenance in the cambium of Arabidopsis hypocotyls, a
      wood-forming lateral meristem, in a similar fashion as in the shoot apical
      meristem. Weak loss-of-function alleles of KNAT1 and STM led to reduced formation
      of xylem fibers - highly differentiated cambial derivatives - whereas cell
      proliferation in the cambium was only mildly affected. In a knat1;stm double
      mutant, xylem fiber differentiation was completely abolished, but residual
      cambial activity was maintained. Expression of early and late markers of xylary
      cell differentiation was globally reduced in the knat1;stm double mutant. KNAT1
      and STM were found to act through transcriptional repression of the meristem
      boundary genes BLADE-ON-PETIOLE 1 (BOP1) and BOP2 on xylem fiber differentiation.
      Together, these data indicate that, in the cambium, KNAT1 and STM, contrary to
      their function in the shoot apical meristem, promote cell differentiation through
      repression of BOP genes.

PMID- 25371366
TI  - TBX1 regulates epithelial polarity and dynamic basal filopodia in the second
      heart field.
AB  - Elongation of the vertebrate heart occurs by progressive addition of second heart
      field (SHF) cardiac progenitor cells from pharyngeal mesoderm to the poles of the
      heart tube. The importance of these cells in the etiology of congenital heart
      defects has led to extensive research into the regulation of SHF deployment by
      signaling pathways and transcription factors. However, the basic cellular
      features of these progenitor cells, including epithelial polarity, cell shape and
      cell dynamics, remain poorly characterized. Here, using immunofluorescence, live
      imaging and embryo culture, we demonstrate that SHF cells constitute an atypical,
      apicobasally polarized epithelium in the dorsal pericardial wall, characterized
      by apical monocilia and dynamic actin-rich basal filopodia. We identify the
      22q11.2 deletion syndrome gene Tbx1, required in the SHF for outflow tract
      development, as a regulator of the epithelial properties of SHF cells. Cell shape
      changes in mutant embryos include increased circularity, a reduced basolateral
      membrane domain and impaired filopodial activity, and are associated with
      elevated aPKCzeta levels. Activation of aPKCzeta in embryo culture similarly
      impairs filopodia activity and phenocopies proliferative defects and ectopic
      differentiation observed in the SHF of Tbx1 null embryos. Our results reveal that
      epithelial and progenitor cell status are coupled in the SHF, identifying control
      of cell shape as a regulatory step in heart tube elongation and outflow tract
      morphogenesis.

PMID- 25371364
TI  - Mesogenin 1 is a master regulator of paraxial presomitic mesoderm
      differentiation.
AB  - Neuromesodermal (NM) stem cells generate neural and paraxial presomitic mesoderm
      (PSM) cells, which are the respective progenitors of the spinal cord and
      musculoskeleton of the trunk and tail. The Wnt-regulated basic helix-loop-helix
      (bHLH) transcription factor mesogenin 1 (Msgn1) has been implicated as a
      cooperative regulator working in concert with T-box genes to control PSM
      formation in zebrafish, although the mechanism is unknown. We show here that, in
      mice, Msgn1 alone controls PSM differentiation by directly activating the
      transcriptional programs that define PSM identity, epithelial-mesenchymal
      transition, motility and segmentation. Forced expression of Msgn1 in NM stem
      cells in vivo reduced the contribution of their progeny to the neural tube, and
      dramatically expanded the unsegmented mesenchymal PSM while blocking
      somitogenesis and notochord differentiation. Expression of Msgn1 was sufficient
      to partially rescue PSM differentiation in Wnt3a(-/-) embryos, demonstrating that
      Msgn1 functions downstream of Wnt3a as the master regulator of PSM
      differentiation. Our data provide new insights into how cell fate decisions are
      imposed by the expression of a single transcriptional regulator.

PMID- 25371367
TI  - Stat3-Efemp2a modulates the fibrillar matrix for cohesive movement of prechordal
      plate progenitors.
AB  - Recently, emerging evidence has shown that Stat3 controls tumor cell migration
      and invasion. However, the molecular mechanisms by which Stat3 controls the cell
      movement remain largely unknown. Embryonic gastrula progenitors display
      coordinated and orientated migration, called collective cell migration.
      Collective cell migration is the simultaneous movement of multiple cells and is
      universally involved in physiological and pathological programs. Stat3 activity
      is required for the migration of gastrula progenitors, but it does not affect
      cell specification, thus suggesting that gastrula movements are an excellent
      model to provide insight into Stat3 control of cell migration in vivo. In this
      study, we reveal a novel mechanism by which Stat3 modulates extracellular matrix
      (ECM) assembly to control the coherence of collective migration of prechordal
      plate progenitors during zebrafish embryonic gastrulation. We show that Stat3
      regulates the expression of Efemp2a in the prechordal plate progenitors that
      migrate anteriorly during gastrulation. Alteration of Stat3-Efemp2a signaling
      activity disrupted the configuration of fibronectin (FN) and laminin (LM)
      matrices, resulting in defective coherence of prechordal plate progenitor
      movements in zebrafish embryos. We demonstrate that Efemp2a acts as a downstream
      effector of Stat3 to promote ECM configuration for coherent collective cell
      migrations in vivo.

PMID- 25371368
TI  - Retinoic acid regulates size, pattern and alignment of tissues at the head-trunk
      transition.
AB  - At the head-trunk transition, hindbrain and spinal cord alignment to occipital
      and vertebral bones is crucial for coherent neural and skeletal system
      organization. Changes in neural or mesodermal tissue configuration arising from
      defects in the specification, patterning or relative axial placement of
      territories can severely compromise their integration and function. Here, we show
      that coordination of neural and mesodermal tissue at the zebrafish head-trunk
      transition crucially depends on two novel activities of the signaling factor
      retinoic acid (RA): one specifying the size and the other specifying the axial
      position relative to mesodermal structures of the hindbrain territory. These
      activities are each independent but coordinated with the well-established
      function of RA in hindbrain patterning. Using neural and mesodermal landmarks we
      demonstrate that the functions of RA in aligning neural and mesodermal tissues
      temporally precede the specification of hindbrain and spinal cord territories and
      the activation of hox transcription. Using cell transplantation assays we show
      that RA activity in the neuroepithelium regulates hindbrain patterning directly
      and territory size specification indirectly. This indirect function is partially
      dependent on Wnts but independent of FGFs. Importantly, RA specifies and patterns
      the hindbrain territory by antagonizing the activity of the spinal cord
      specification gene cdx4; loss of Cdx4 rescues the defects associated with the
      loss of RA, including the reduction in hindbrain size and the loss of posterior
      rhombomeres. We propose that at the head-trunk transition, RA coordinates
      specification, patterning and alignment of neural and mesodermal tissues that are
      essential for the organization and function of the neural and skeletal systems.

PMID- 25371369
TI  - Dominant and context-specific control of endodermal organ allocation by Ptf1a.
AB  - The timing and gene regulatory logic of organ-fate commitment from within the
      posterior foregut of the mammalian endoderm is largely unexplored. Transient
      misexpression of a presumed pancreatic-commitment transcription factor, Ptf1a, in
      embryonic mouse endoderm (Ptf1a(EDD)) dramatically expanded the pancreatic gene
      regulatory network within the foregut. Ptf1a(EDD) temporarily suppressed Sox2
      broadly over the anterior endoderm. Pancreas-proximal organ territories underwent
      full tissue conversion. Early-stage Ptf1a(EDD) rapidly expanded the endogenous
      endodermal Pdx1-positive domain and recruited other pancreas-fate-instructive
      genes, thereby spatially enlarging the potential for pancreatic multipotency.
      Early Ptf1a(EDD) converted essentially the entire glandular stomach, rostral
      duodenum and extrahepatic biliary system to pancreas, with formation of many
      endocrine cell clusters of the type found in normal islets of Langerhans. Sliding
      the Ptf1a(EDD) expression window through embryogenesis revealed differential
      temporal competencies for stomach-pancreas respecification. The response to later
      stage Ptf1a(EDD) changed radically towards unipotent, acinar-restricted
      conversion. We provide strong evidence, beyond previous Ptf1a inactivation or
      misexpression experiments in frog embryos, for spatiotemporally context-dependent
      activity of Ptf1a as a potent gain-of-function trigger of pro-pancreatic
      commitment.

PMID- 25371371
TI  - CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance
      but do not supplant MYD88(L265P) -directed survival signalling in Waldenstrom
      macroglobulinaemia cells.
AB  - CXCR4(WHIM) frameshift and nonsense mutations follow MYD88(L265P) as the most
      common somatic variants in Waldenstrom Macroglobulinaemia (WM), and impact
      clinical presentation and ibrutinib response. While the nonsense (CXCR4(S338X) )
      mutation has been investigated, little is known about CXCR4 frameshift (CXCR4(FS)
      ) mutations. We engineered WM cells to express CXCR4(FS) mutations present in
      patients, and compared their CXCL12 (SDF-1a) induced signalling and ibrutinib
      sensitivity to CXCR4(wild-type (WT)) and CXCR4(S338X) cells. Following CXCL12
      stimulation, CXCR4(FS) and CXCR4(S338X) WM cells showed impaired CXCR4 receptor
      internalization, and enhanced AKT1 (also termed AKT) and MAPK1 (also termed ERK)
      activation versus CXCR(WT) cells (P < 0.05), though MAPK1 activation was more
      prolonged in CXCR4(S338X) cells (P < 0.05). CXCR4(FS) and CXCR4(S338X) cells, but
      not CXCR4(WT) cells, were rescued from ibrutinib-triggered apoptosis by CXCL12
      that was reversed by AKT1, MAPK1 or CXCR4 antagonists. Treatment with an
      inhibitor that blocks MYD88(L265P) signalling triggered similar levels of
      apoptosis that was not abrogated by CXCL12 treatment in CXCR4(WT) and CXCR4(WHIM)
      cells. These studies show a functional role for CXCR4(FS) mutations in WM, and
      provide a framework for the investigation of CXCR4 antagonists with ibrutinib in
      CXCR4(WHIM) -mutated WM patients. Direct inhibition of MYD88(L265P) signalling
      overcomes CXCL12 triggered survival effects in CXCR4(WHIM) -mutated cells
      supporting a primary role for this survival pathway in WM.

PMID- 25371370
TI  - The UNC-6/Netrin receptors UNC-40/DCC and UNC-5 inhibit growth cone filopodial
      protrusion via UNC-73/Trio, Rac-like GTPases and UNC-33/CRMP.
AB  - UNC-6/Netrin is a conserved axon guidance cue that can mediate both attraction
      and repulsion. We previously discovered that attractive UNC-40/DCC receptor
      signaling stimulates growth cone filopodial protrusion and that repulsive UNC-40
      UNC-5 heterodimers inhibit filopodial protrusion in C. elegans. Here, we identify
      cytoplasmic signaling molecules required for UNC-6-mediated inhibition of
      filopodial protrusion involved in axon repulsion. We show that the Rac-like
      GTPases CED-10 and MIG-2, the Rac GTP exchange factor UNC-73/Trio, UNC-44/Ankyrin
      and UNC-33/CRMP act in inhibitory UNC-6 signaling. These molecules were required
      for the normal limitation of filopodial protrusion in developing growth cones and
      for inhibition of growth cone filopodial protrusion caused by activated MYR::UNC
      40 and MYR::UNC-5 receptor signaling. Epistasis studies using activated CED-10
      and MIG-2 indicated that UNC-44 and UNC-33 act downstream of the Rac-like GTPases
      in filopodial inhibition. UNC-73, UNC-33 and UNC-44 did not affect the
      accumulation of full-length UNC-5::GFP and UNC-40::GFP in growth cones,
      consistent with a model in which UNC-73, UNC-33 and UNC-44 influence cytoskeletal
      function during growth cone filopodial inhibition.

PMID- 25371372
TI  - Intrahepatic cholestasis of pregnancy and timing of delivery.
AB  - OBJECTIVE: We examined the morbidities from delivery at earlier gestational ages
      versus intrauterine fetal demise (IUFD) for women with intrahepatic cholestasis
      of pregnancy (ICP) to determine the optimal gestational age for delivery.
      METHODS: A decision-analytic model was created to compare delivery at 35 through
      38 weeks gestation for different delivery strategies: (1) empiric steroids; (2)
      steroids if fetal lung maturity (FLM) negative; (3) wait a week and retest if FLM
      negative; or (4) deliver immediately. Literature review identified 18 studies
      that estimated IUFD in ICP; we used the mean rate, 1.74%, and assumed a uniform
      distribution from 34 to 40 weeks gestation. Large cohort data was used to
      calculate neonatal morbidity rates at each gestational age. Maternal and neonatal
      quality-adjusted life years (QALYs) were combined. Univariate sensitivity and
      Monte Carlo analyses were performed to test for robustness. RESULTS: Immediate
      delivery at 36 weeks without FLM testing and steroid administration was the
      optimal strategy as compared to delivery at 36 weeks with steroids (+47 QALYs)
      and as compared to immediate delivery at 35 weeks (+210 QALYs). Our results were
      robust up to a 30% increase in the rate of IUFD. CONCLUSION: Immediate delivery
      at 36 weeks in women with ICP is the optimal delivery strategy.

PMID- 25371373
TI  - Healthcare Resource Utilization in Patients Receiving Omalizumab for Allergic
      Asthma in a Real-World Setting.
AB  - INTRODUCTION: Inadequately controlled asthma is associated with increased
      healthcare resource utilization. The eXpeRience registry was initiated to
      evaluate real-world outcomes in patients receiving omalizumab for uncontrolled
      persistent allergic asthma. The current analysis of data from the eXpeRience
      registry focuses on healthcare resource utilization and on absences from work or
      school. METHODS: The eXpeRience was a 2-year, multinational, non-interventional,
      observational registry conducted to investigate real-world outcomes among
      patients receiving omalizumab in accordance with country-specific prescribing
      criteria for the treatment of uncontrolled persistent allergic asthma. Asthma
      related healthcare resource utilization (hospitalizations, emergency room visits
      or unscheduled-asthma-related doctor visits or interventions) and absences from
      work or school were assessed pre-treatment (12-month data were collected
      retrospectively at baseline) and at months 12 and 24 after the initiation of
      omalizumab treatment. Serious adverse event (SAE) data were also assessed.
      RESULTS: A total of 943 patients (mean age 45 years; female 65%) were enrolled in
      the registry. Overall, the mean (standard deviation [SD]) number of asthma
      related medical healthcare uses per patient decreased from 6.2 (6.97) during the
      pre-treatment period to 1.0 (1.96) and 0.5 (1.28) at months 12 and 24,
      respectively. The mean (SD) number of work or school days missed due to asthma
      was also lower at months 12 (3.5 [17.28] and 1.6 [4.28], respectively) and 24
      (1.0 [4.66] and 1.9 [5.46], respectively) compared with the pre-treatment period
      (26.4 [49.61] and 20.7 [27.49], respectively). The nature and frequency of SAEs
      in the eXpeRience registry were comparable to that seen in interventional
      clinical trials with omalizumab. CONCLUSION: The results of the eXpeRience
      registry indicate that omalizumab is associated with reductions in healthcare
      utilization, and in the number of days of absence from work or school, in
      patients with uncontrolled persistent allergic asthma in the real-world setting.
      FUNDING: Novartis Pharma AG, Basel, Switzerland.

PMID- 25371375
TI  - A poly(3,4-ethylenedioxypyrrole)-Au@WO3 -based electrochromic pseudocapacitor.
AB  - A poly(3,4-ethylenedioxypyrrole)-gold nanoparticle (Au)-tungsten oxide (PEDOP
      Au@WO3 ) electrochromic supercapacitor electrode capable of optically modulating
      solar energy while simultaneously storing/releasing energy (in the form of
      charge) was fabricated for the first time. WO3 fibers, 50 to 200 nm long and 20
      to 60 nm wide, were synthesized by a hydrothermal route and were
      electrophoretically deposited on a conducting substrate. Au nanoparticles and
      PEDOP were coated over WO3 to yield the PEDOP-Au@WO3 hybrid electrode. The
      inclusion of Au in the hybrid was confirmed by X-ray diffraction, Raman
      spectroscopy, and energy-dispersive X-ray analyses. The nanoscale electronic
      conductivity, coloration efficiency, and transmission contrast of the hybrid were
      found to be significantly greater than those of pristine WO3 and PEDOP. The
      hybrid showed a high specific discharge capacitance of 130 F g(-1) during
      coloration, which was four and ten times greater than the capacitance achieved in
      WO3 or PEDOP, respectively. We also demonstrate the ability of the PEDOP-Au@WO3
      hybrid, relative to pristine PEDOP, to perform as a superior counter electrode in
      a solar cell, which is attributed to a higher work function. The capacitance and
      redox switching capability of the hybrid decreases insignificantly with cycling,
      thus establishing the viability of this multifunction hybrid for next-generation
      sustainable devices such as electrochromic psuedocapacitors because it can
      concurrently conserve and store energy. 

PMID- 25371374
TI  - Genetic simulation tools for post-genome wide association studies of complex
      diseases.
AB  - Genetic simulation programs are used to model data under specified assumptions to
      facilitate the understanding and study of complex genetic systems. Standardized
      data sets generated using genetic simulation are essential for the development
      and application of novel analytical tools in genetic epidemiology studies. With
      continuing advances in high-throughput genomic technologies and generation and
      analysis of larger, more complex data sets, there is a need for updating current
      approaches in genetic simulation modeling. To provide a forum to address current
      and emerging challenges in this area, the National Cancer Institute (NCI)
      sponsored a workshop, entitled "Genetic Simulation Tools for Post-Genome Wide
      Association Studies of Complex Diseases" at the National Institutes of Health
      (NIH) in Bethesda, Maryland on March 11-12, 2014. The goals of the workshop were
      to (1) identify opportunities, challenges, and resource needs for the development
      and application of genetic simulation models; (2) improve the integration of
      tools for modeling and analysis of simulated data; and (3) foster collaborations
      to facilitate development and applications of genetic simulation. During the
      course of the meeting, the group identified challenges and opportunities for the
      science of simulation, software and methods development, and collaboration. This
      paper summarizes key discussions at the meeting, and highlights important
      challenges and opportunities to advance the field of genetic simulation. 

PMID- 25371376
TI  - H2O2 Exposure Affects Myotube Stiffness and Actin Filament Polymerization.
AB  - Skeletal muscles often experience oxidative stress in anaerobic metabolism and
      ischemia-reperfusion. This paper reports how oxidative stress affects the
      stiffness of cultured murine myotubes and their actin filaments polymerization
      dynamics. H2O2 was applied as an extrinsic oxidant to C2C12 myotubes. Atomic
      force microscopy results showed that short exposures to H2O2 apparently increased
      the stiffness of myotubes, but that long exposures made the cells softer. The
      turning point seemed to take place somewhere between 1 and 2 h of H2O2 exposure.
      We found that the stiffness change was probably due to actin filaments being
      favored for depolymerization after prolong H2O2 treatments, especially when the
      exposure duration exceeded 1 h and the exposure concentration reached 1.0 mM.
      Such depolymerization effect was associated with the down-regulation of thymosin
      beta 4, as well as the up-regulation of both cofilin2 and profilin1 after prolong
      H2O2 treatments. 

PMID- 25371377
TI  - Fully glycerol-independent microbial production of 1, 3-propanediol via non
      natural pathway: paving the way to success with synthetic tiles.

PMID- 25371380
TI  - Redefining Risk and Benefit: Understanding the Decision to Undergo Contralateral
      Prophylactic Mastectomy.
AB  - Rates of contralateral prophylactic mastectomy (CPM) among unilateral breast
      cancer patients are rapidly increasing; however, there are little data
      documenting the decision-making process of patients with no known BRCA mutations,
      who elect this more aggressive treatment. We conducted semistructured interviews
      with nine newly diagnosed patients who elected CPM over other surgical options.
      Using grounded theory, we analyzed interview data to identify influential
      decision-making factors by prevalence and intensity across participants. Decision
      making factors included subjective evaluations of risk and benefit, avoidance of
      future breast cancer surveillance and accompanying worry, and desire to maintain
      (or improve) breast appearance. Based solely on survival benefit, the decision to
      undergo CPM might be viewed as unnecessary or even misguided. However, our
      findings show the importance of psychosocial factors in patients' assessments of
      risk and benefit, and support the need for additional patient-provider
      communication regarding these factors. 

PMID- 25371381
TI  - Clinical Expert or Service Provider? Physicians' Identity Work in the Context of
      Counterprofessional Patient Requests.
AB  - Researchers often discuss patient-related outcomes of the shift from the
      paternalistic physician-to-patient model to those of patient participation, yet
      little is known about the impact of patient participation on physicians'
      professional identity. In this study, we explored the context of
      counterprofessional patient requests in which patient participation conflicts
      with medical professionalism. We interviewed 34 physicians, of whom 14 were
      family physicians and pediatricians, and 20 were specialists in various fields.
      Data were analyzed by a grounded theory approach. Our findings indicate that
      physicians experienced conflicts between their identities as clinical experts,
      caretakers, service providers, and resource allocators. To cope with the
      resulting tension, physicians used the strategies of hierarchy setting,
      integrating, incorporating the patient, and changing the meaning of an identity
      or the event. All strategies were implemented by cognitive and relational
      tactics. 

PMID- 25371379
TI  - Tubulointerstitial fibrosis in patients with IgG4-related kidney disease:
      pathological findings on repeat renal biopsy.
AB  - Renal parenchymal lesions in patients with IgG4-related kidney disease (IgG4-RKD)
      are characterized by tubulointerstitial nephritis with storiform fibrosis and
      infiltration by high numbers of IgG4-positive plasma cells. The aim of this study
      was to evaluate the clinical and pathological effects of corticosteroid therapy
      in patients with IgG4-RKD. Of six patients who were diagnosed with IgG4-RKD, four
      patients underwent re-biopsy at approximately 30-50 days after corticosteroid
      therapy was initiated. Based on the classification of Yamaguchi et al., the
      degree of tubulointerstitial fibrosis was classified before and after therapy. In
      addition, tubulointerstitial expression patterns of alpha-smooth muscle actin
      (alpha-SMA), collagen I, III, and IV protein, and connective tissue growth factor
      (CTGF) mRNA were examined. Histopathological findings before treatment showed
      alpha-SMA-positive myofibroblasts in the lesion, and CTGF mRNA-positive cells
      were found in the cellular infiltrate. Although corticosteroid therapy improved
      serum creatinine clinically, the stage of fibrosis advanced pathologically as
      evidenced by increased staining for collagen I and III. However, the number of
      IgG4-positive plasma cells decreased, and CTGF mRNA expression reduced. In other
      words, fibrosis had advanced from the time of extensive cell infiltration in
      patients with IgG4-RKD and inflammation was relieved by corticosteroid. A reduced
      number of positive CTGF mRNA expression cells in repeat biopsies indicated that
      the fibrosis process was terminated by corticosteroid therapy. We propose that
      corticosteroid therapy could terminate the pathway of active fibrosis, thereby
      inhibiting progression to renal dysfunction.

PMID- 25371382
TI  - Psychological Coercion in Human Trafficking: An Application of Biderman's
      Framework.
AB  - This study examined coercive conditions experienced by trafficked persons in the
      context of Biderman's theory of coercion. We conducted semi-structured interviews
      with 12 adult women trafficked into Los Angeles County, from 10 countries, for
      domestic work and/or sex work. Participants described health problems they
      experienced in relation to their trafficking experience and their perceptions of
      conditions that caused health problems. Utilizing a framework analysis approach,
      we analyzed themes using Biderman's framework. Participants reported experiencing
      the range of nonphysical coercive tactics outlined by Biderman, including
      isolation, monopolization of perception, induced debility or exhaustion, threats,
      occasional indulgences, demonstration of omnipotence, degradation, and
      enforcement of trivial demands. Our analysis demonstrates how these coercion
      tactics reinforced the submission of trafficked persons to their traffickers even
      in the absence of physical force or restraints. Such psychological abuse creates
      extreme stress that can lead to acute and chronic, physical and mental health
      problems. 

PMID- 25371383
TI  - Excitatory and inhibitory brain metabolites as targets of motor cortex
      transcranial direct current stimulation therapy and predictors of its efficacy in
      fibromyalgia.
AB  - OBJECTIVE: Transcranial direct current stimulation (tDCS) has been shown to
      improve pain symptoms in fibromyalgia (FM), a central pain syndrome whose
      underlying mechanisms are not well understood. This study was undertaken to
      explore the neurochemical action of tDCS in the brain of patients with FM, using
      proton magnetic resonance spectroscopy (1H-MRS). METHODS: Twelve patients with FM
      underwent sham tDCS over the left motor cortex (anode placement) and
      contralateral supraorbital cortex (cathode placement) for 5 consecutive days,
      followed by a 7-day washout period and then active tDCS for 5 consecutive days.
      Clinical pain assessment and 1H-MRS testing were performed at baseline, the week
      following the sham tDCS trial, and the week following the active tDCS trial.
      RESULTS: Clinical pain scores decreased significantly between the baseline and
      active tDCS time points (P = 0.04). Levels of glutamate + glutamine (Glx) in the
      anterior cingulate were significantly lower at the post-active tDCS assessment
      compared with the post-sham tDCS assessment (P = 0.013), and the decrease in Glx
      levels in the thalami between these time points approached significance (P =
      0.056). From baseline to the post-sham tDCS assessment, levels of N
      acetylaspartate (NAA) in the posterior insula increased significantly (P =
      0.015). There was a trend toward increased levels of gamma-aminobutyric acid
      (GABA) in the anterior insula after active tDCS, compared with baseline (P =
      0.064). Baseline anterior cingulate Glx levels correlated significantly with
      changes in pain score, both for the time period from baseline to sham tDCS (beta1
      = 1.31, P < 0.001) and for the time period from baseline to active tDCS (beta1=
      1.87, P < 0.001). CONCLUSION: The present findings suggest that GABA, Glx, and
      NAA play an important role in the pathophysiology of FM and its modulation by
      tDCS.

PMID- 25371384
TI  - Editorial: observational studies, time-dependent confounding, and marginal
      structural models.

PMID- 25371385
TI  - Self-assembled alluaudite Na(2)Fe(3-x)Mn(x)(PO4)(3) micro/nanocompounds for
      sodium-ion battery electrodes: a new insight into their electronic and geometric
      structure.
AB  - A series of alluaudite Na2 Fe3-x Mnx (PO4 )3 microcompounds, which self-assembled
      from primary nanorods, were prepared successfully through a solvothermal method.
      As a promising candidate cathode for sodium-ion batteries, it is necessary to
      obtain a deeper understanding of the relationship between the structure and
      physicochemical properties of these materials. The local electronic and geometric
      environments were systematically investigated, for the first time, by using a
      combination of soft/hard X-ray absorption, IR, and Mossbauer spectroscopy. The
      results show that the electrochemical performance is not only associated with
      morphology, but also with the electronic and crystalline structure. With the
      introduction of manganese into the lattice, the long-range order maintains the
      isostructural framework and the lattice parameters expand as expected. However,
      for short-range order, PO4 tetrahedra and MO6 octahedra (M=Fe and Mn) become more
      severely distorted as a function of Mn concentration. Meanwhile, larger MnO6
      octahedra will compress the space of FeO6 octahedra, which will result in
      stronger core/electron-electron interactions for Fe, as characterized by
      hard/soft X-ray absorption spectra. These slight changes in the electronic and
      local structures lead to different electrochemical performances with changes to
      the manganese content. Moreover, other physicochemical properties, such as
      magnetic behavior, are also confirmed to be correlated with these different
      electron interactions and local geometric environments. 

PMID- 25371386
TI  - Development and validation of an LC-MS/MS method after chiral derivatization for
      the simultaneous stereoselective determination of methylenedioxy-methamphetamine
      (MDMA) and its phase I and II metabolites in human blood plasma.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a racemic drug of abuse and
      its two enantiomers are known to differ in their dose-response curves. The S
      enantiomer was shown to be eliminated at a higher rate than the R-enantiomer. The
      most likely explanation for this is a stereoselective metabolism also claimed in
      in vitro studies. Urinary excretion studies showed that the main metabolites in
      humans are 4-hydroxy 3-methoxymethamphetamine (HMMA) 4-sulfate, HMMA 4
      glucuronide and 3,4-dihydroxymethamphetamine (DHMA) 3-sulfate. For
      stereoselective pharmacokinetic analysis of phase I and phase II metabolites in
      human blood plasma useful analytical methods are needed. Therefore the aim of the
      presented study was the development and validation of a stereoselective liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous
      quantification of MDMA, 3,4-methylenedioxyamphetamine, DHMA, DHMA 3-sulfate,
      HMMA, HMMA 4-glucuronide, HMMA 4-sulfate, and 4-hydroxy 3-methoxyamphetamine in
      blood plasma for evaluation of the stereoselective pharmacokinetics in humans.
      Blood plasma samples were prepared by simple protein precipitation and afterwards
      all analytes were derivatized using N-(2,4-dinitro-5-fluorophenyl) L-valinamide
      resulting in the formation of diastereomers which were easily separable on
      standard reverse phase stationary phases. This simple and fast method was
      validated according to international guidelines including specificity, recovery,
      matrix effects, accuracy and precision, stabilities, and limits of
      quantification. The method proved to be selective, sensitive, accurate and
      precise for all tested analytes except for DHMA.

PMID- 25371387
TI  - Long-term tumor remission under trastuzumab treatment for HER2 positive
      metastatic breast cancer - results from the HER-OS patient registry.
AB  - BACKGROUND: In this study, we examined patients who had non-progressive disease
      for at least 2 years after diagnosis of inoperable locoregional recurrent or
      metastatic breast cancer under continuous trastuzumab treatment. Our primary goal
      was to assess the long-term outcome of patients with durable response to
      trastuzumab. METHODS: 268 patients with HER2-positive inoperable locally
      recurrent or metastatic breast cancer and non-progressive disease for at least 2
      years under trastuzumab treatment were documented retrospectively or
      prospectively in the HER-OS registry, an online documentation tool, between
      December 2006 and September 2010 by 71 German oncology centers. The study end
      point was time to tumor progression. RESULTS: Overall, 47.1% of patients (95%
      confidence interval (CI): 39.9-54.1%) remained in remission for more than 5
      years, while the median time to progression was 4.5 years (95% CI: 4.0-6.6
      years). Lower age (<50 years) and good performance status (ECOG 0) at time of
      trastuzumab treatment initiation as well as complete remission after initial
      trastuzumab treatment were associated with longer time to progression.
      Interruption of trastuzumab therapy correlated with shorter time to progression.
      CONCLUSIONS: HER2-positive patients, who initially respond to palliative
      treatment with trastuzumab, can achieve a long-term tumor remission of several
      years.

PMID- 25371388
TI  - Fetal alcohol spectrum disorders among children in a Brazilian orphanage.
AB  - BACKGROUND: The objective was to investigate the frequency of fetal alcohol
      spectrum disorders (FASD) and ophthalmologic anomalies in orphanage children in
      Brazil. METHODS: A prospective study was performed on 94 children living in an
      orphanage in Brazil. The children were examined by a multidisciplinary team
      consisting of specialists in pediatrics, neurology, psychology, neuropsychiatry,
      and ophthalmology. RESULTS: The main reasons for living in the orphanage, in 61%
      of the children, were negligence, child abuse, and abandonment. Of all the
      children studied, 50% had mothers with known alcohol abuse and 47% had one or
      more diagnoses of neurodevelopmental/behavioral and/or cognitive deficits.
      General developmental delay was found in 18%, intellectual disability in 3%,
      cognitive impairment in 27%, attention-deficit/hyperactivity disorder in 14%, and
      autism in 3%. Altogether 17% had FASD, comprising three children with fetal
      alcohol syndrome (FAS), six with partial FAS, and seven with alcohol-related
      neurodevelopmental disorder. 16% had ophthalmological findings such as poor
      vision, strabismus, and dysmorphology of the optic nerves. Twenty-eight children
      (30%) were adopted from the orphanage; of these, six had FASD (two FAS, three
      partial FAS, one alcohol-related neurodevelopmental disorder), five had attention
      deficit/hyperactivity disorder, and eight had developmental delay. CONCLUSION:
      Nearly half of the children living in the orphanage had neurodevelopmental
      disorders and a considerable number showed signs of damage from prenatal alcohol
      exposure. A broader look at the problem of FASD in Brazil and other South
      American countries is desirable to document the burden of disease and provide
      data for targeting prevention efforts.

PMID- 25371389
TI  - Rebuilding health services in Gaza won't be possible while Israel maintains
      blockade, says report.

PMID- 25371390
TI  - Infrared-metabolomics approach in detecting changes in Andrographis paniculata
      metabolites due to different harvesting ages and times.
AB  - BACKGROUND: The metabolite changes in three germplasm accessions of Malaysia
      Andrographis paniculata (Burm. F.) Nees, viz. 11265 (H), 11341 (P) and 11248 (T),
      due to their different harvesting ages and times were successfully evaluated by
      attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy
      and translated through multivariate data analysis of principal component analysis
      (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). This
      present study revealed the feasibility of ATR-FTIR in detecting the trend changes
      of the major metabolites - andrographolide and neoandrographolide - functional
      groups in A. paniculata leaves of different accessions. The harvesting parameter
      was set at three different ages of 120, 150 and 180 days after transplanting
      (DAT) and at two different time sessions of morning (7:30-10:30 am) and evening
      (2:30-5.30 pm). RESULTS: OPLS-DA successfully discriminated the A. paniculata
      crude extracts into groups of which the main constituents - andrographolide and
      neoandrographolide - could be mainly observed in the morning session of 120 DAT
      for P and T, while H gave the highest intensities of these constituents at 150
      DAT. CONCLUSION: The information extracted from ATR-FTIR data through OPLS-DA
      could be useful in tailoring this plant harvest stage in relation to the content
      of its two major diterpene lactones: andrographolide and neoandrographolide.

PMID- 25371391
TI  - New synthesis on the basis 2-allyloxy chalcone and NMR studies its some
      derivatives.
AB  - Synthesis and NMR investigations of cyclohexenone, flavanone, isoxazol and
      indazole derivatives of (2E)-3-[2-(allyloxy)-5-bromophenyl]-1-(2-hydroxy-5
      methylphenyl)-2-propen-1-one (I, chalcone) have been carried out. The results
      confirm the formation of O-H***O type intramolecular hydrogen bond and
      intramolecular cyclization in the (2E)-3-[2-(allyloxy)-5-bromophenyl]-1-(2
      hydroxy-5-methylphenyl)-2-propen-1-one (I), the presence of conformational and
      keto-enol tautomeric transitions in the 6-acetyl-5-[2-(allyloxy)-5-bromophenyl]-3
      (2-hydroxy-5-methylphenyl)-2-cyclohexen-1-one (II), conformational transitions in
      the 2-{4-[2-(allyloxy)-5-bromophenyl]-3-methyl-4.5-dihydro-1.2-benzisoxazol-6-yl}
      4-methylphenol (III) and 2-{4-[2-(allyloxy)-5-bromophenyl]-3-methyl-4.5-dihydro
      1H-indazol-6-yl}-4-methylphenol (IV). The conformational and keto-enol
      tautomerism in the investigated compounds have been also confirmed by chemical
      methods.

PMID- 25371392
TI  - Reply: To PMID 24782356.

PMID- 25371393
TI  - HepaRG cells as human-relevant in vitro model to study the effects of
      inflammatory stimuli on cytochrome P450 isoenzymes.
AB  - The suppression of hepatic cytochrome P450 (P450) expression during inflammatory
      and infectious diseases and the relief of this suppression by successful disease
      treatment have been previously demonstrated to impact drug disposition. To
      address this clinically relevant phenomenon preclinically, the effect of
      proinflammatory cytokines on P450 isoenzymes in human hepatocytes has been
      examined by several researchers. In the present study we used the human hepatoma
      cell line (HepaRG) and cryopreserved primary human hepatocytes to investigate the
      effects of various inflammatory stimuli on P450 levels with the aim of further
      characterizing HepaRG cells as a useful surrogate for primary hepatocytes. In
      this study, HepaRG cells were exposed to bacterial lipopolysaccharide (LPS),
      interleukin-6 (IL-6), and interleukin-18 (IL-18) for 48 or 72 hours. The effects
      on CYP1A2, CYP2B6, and CYP3A4 mRNA and catalytic activity (phenacetin-O
      deethylase, bupropion-hydroxylase, and midazolam-1'-hydroxylase) were measured.
      Cryopreserved pooled plateable hepatocytes were also exposed to IL-6 or IL-18 for
      48 hours, and the effects on CYP1A2, CYP2B6, and CYP3A4 mRNA levels were
      measured. The exposure of HepaRG cells to IL-6 and LPS resulted in suppression of
      CYP1A2, CYP2B6, and CYP3A4 mRNA levels as well as their catalytic activities.
      However, no suppression of P450 activities or mRNA levels was observed after
      exposure to IL-18. Similar results on CYP1A2, CYP2B6, and CYP3A4 mRNA levels were
      observed with primary hepatocytes. The present study indicates that different
      proinflammatory mediators influence the expression of P450 differentially and
      that HepaRG cells may be used as an alternative to human hepatocytes for studies
      on cytokine-mediated suppression of drug-metabolizing enzymes. 

PMID- 25371394
TI  - Think tank calls for new GP contracts to encourage innovation.

PMID- 25371396
TI  - Insulin-like growth factor-1 and insulin-like growth factor-binding protein-3
      concentrations in children with obstructive sleep apnea-hypopnea syndrome.
AB  - BACKGROUND: The aim of this study was to assess insulin-like growth factor-1 (IGF
      1) and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations in
      children with obstructive sleep apnea-hypopnea syndrome (OSAHS) and to compare
      the results according to disease severity and duration. METHODS: Fifty-one
      children with OSAHS underwent polysomnography and were classified as having mild,
      moderate, or severe disease. All children underwent bilateral
      tonsillectomy/adenoidectomy or adenoidectomy. IGF-1 and IGFBP-3 concentrations
      were assessed before surgery and 3 and 6 months after surgery. RESULTS: Before
      surgery, IGF-1 and IGFBP-3 concentrations were significantly higher (P < .05) in
      the < 5-y group (125.20 +/- 42.38 MUg/L and 2.00 +/- 0.54 mg/L) compared with the
      >= 5-y group (61.92 +/- 19.07 MUg/L and 1.20 +/- 0.37 mg/L). After surgery,
      concentrations significantly increased (P < .05) in both groups, but remained
      lower in the >= 5-y group. Before surgery, there were no significant differences
      in IGF-1 (mild: 93.82 +/- 37.52 mg/L; moderate: 109.06 +/- 58.42 mg/L; severe:
      73.88 +/- 28.51 mg/L) and IGFBP-3 (mild: 1.76 +/- 0.57 mg/L; moderate: 1.67 +/-
      0.72 mg/L; severe: 1.33 +/- 0.45 mg/L) concentrations by severity. After surgery,
      concentrations significantly increased (P < .05) in both groups, but did not
      differ by severity. After adjusting for time after surgery, disease duration,
      apnea-hypopnea index, time spent at SpO2 < 90%, and body mass index Z score, IGF
      1 and IGFBP-3 concentrations significantly decreased with every year of age.
      CONCLUSIONS: These results suggest that disease duration, but not severity,
      affects the concentrations of 2 important mediators of growth/development (IGF-1
      and IGFBP-3) in children with OSAHS before and after surgery.

PMID- 25371395
TI  - Modular analysis of peripheral blood gene expression in rheumatoid arthritis
      captures reproducible gene expression changes in tumor necrosis factor
      responders.
AB  - OBJECTIVE: To establish whether the analysis of whole-blood gene expression is
      useful in predicting or monitoring response to anti-tumor necrosis factor (anti
      TNF) therapy in patients with rheumatoid arthritis (RA). METHODS: Whole-blood RNA
      (using a PAXgene system to stabilize whole-blood RNA in the collection tube) was
      obtained at baseline and at 14 weeks from 3 independent cohorts, consisting of a
      combined total of 240 RA patients who were beginning therapy with anti-TNF. We
      used an approach to gene expression analysis that is based on modular patterns of
      gene expression, or modules. RESULTS: Good and moderate responders according to
      the European League Against Rheumatism criteria exhibited highly significant and
      consistent changes in multiple gene expression modules after 14 weeks of therapy,
      as demonstrated by hypergeometric analysis. Strikingly, nonresponders exhibited
      very little change in any modules, despite exposure to TNF blockade. These
      patterns of change were highly consistent across all 3 cohorts, indicating that
      immunologic changes after TNF treatment are specific to the combination of both
      drug exposure and responder status. In contrast, modular patterns of gene
      expression did not exhibit consistent differences between responders and
      nonresponders at baseline in the 3 study cohorts. CONCLUSION: These data provide
      evidence that using gene expression modules related to inflammatory disease may
      provide a valuable method for objective monitoring of the response of RA patients
      who are treated with TNF inhibitors.

PMID- 25371397
TI  - Ventilatory efficiency before and after lung volume reduction surgery.
AB  - BACKGROUND: Lung volume reduction surgery (LVRS) has been shown to improve the
      clearance of carbon dioxide and minute ventilation (VE) in select patients with
      COPD. One variable often assessed in COPD is ventilatory efficiency (VE/VCO2 ).
      METHODS: We compared 55 LVRS subjects with 25 controls from the National
      Emphysema Treatment Trial. VE/VCO2 was calculated from cardiopulmonary exercise
      testing at baseline and 6-months. We sought to assess VE/VCO2 changes with LVRS
      compared with controls who only received standard medical care. RESULTS: At 6
      months, the LVRS group significantly increased peak VO2 , work load, VE, VCO2 ,
      and tidal volume while lowering peak and lowest VE/VCO2 (improved ventilatory
      efficiency) and end-tidal carbon dioxide pressure. The control group did not
      display these changes. The changes were greatest in the LVRS subjects who
      improved their exercise capacity after surgery (> 10 W). CONCLUSIONS: The changes
      were greatest in the LVRS subjects who showed the most functional improvement,
      indicating an association of improved ventilation with improved functional
      outcome.

PMID- 25371398
TI  - Cyclic variation in heart rate score by holter electrocardiogram as screening for
      sleep-disordered breathing in subjects with heart failure.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is critically associated with
      cardiovascular mortality and morbidity, especially in patients with heart failure
      (HF). However, the majority of SDB patients remain undiagnosed. In contrast,
      abnormality in heart rate variability has been reported in patients with SDB. To
      explore an efficient electrocardiogram (ECG)-based screening tool for SDB, we
      examined the usefulness of cyclic variation in heart rate score (CVHRS) by Holter
      ECG in subjects with HF. METHODS: In this study, 102 subjects with HF were
      enrolled. We simultaneously performed Holter ECG with overnight portable sleep
      monitoring, and we measured the respiratory disturbance index (RDI) and CVHRS. We
      determined the temporal position of the individual dips comprising the CVHRS
      using time-domain methods. CVHRS was measured as cyclic and autocorrelated dips
      in smoothed interbeat interval time series. RESULTS: There were 25 subjects with
      severe SDB (RDI >= 30 events/h) and 77 subjects with none-to-moderate SDB (0 <=
      RDI < 30 events/h). There was a significant positive correlation between CVHRS
      and RDI (r = 0.60, P < .001). In receiver operating characteristic analysis,
      CVHRS (cutoff of 30 events/h) identified severe SDB with a sensitivity of 82%, a
      specificity of 77%, and an area under the curve of 0.83. CONCLUSIONS: CVHRS
      determined by Holter ECG is a useful screening index for severe SDB in subjects
      with HF.

PMID- 25371399
TI  - Description and microbiology of endotracheal tube biofilm in mechanically
      ventilated subjects.
AB  - BACKGROUND: A biofilm is found on the inner side of endotracheal tubes (ETT) in
      mechanically ventilated patients, but its features and role in pneumonia remain
      unclear. METHODS: This prospective, observational, monocentric study included
      critically ill ventilated subjects. Measurement of the ETT inner volume was first
      performed before extubation using the acoustic reflection method. After
      extubation, the biofilm was studied by means of optical and atomic force
      microscopy. Bacteriological analysis was then performed and compared with
      clinical documentation. RESULTS: Twenty-four subjects were included. Duration of
      intubation lasted from 2 to 79 d (mean +/- SD: 11 +/- 15 d). The mean percentage
      of ETT volume loss evaluated in situ (n = 21) was 7.1% and was not linked with
      the duration of intubation. Analyses with atomic force microscopy (n = 6) showed
      a full coverage of the inner part of the tube with biofilm, even after saline
      rinse. Its thickness ranged from 0.8 to 5 MUm. Bacteriological cultures of the
      biofilm (n = 22) often showed the same bacteria as in tracheal secretions,
      especially for pathogenic organisms. Pseudomonas aeruginosa and Candida albicans
      were among the most frequent microorganisms. In subjects who had experienced a
      successfully treated episode of ventilator-associated pneumonia (n = 5), the
      responsible bacteria were still present in the biofilm. CONCLUSIONS: ETT biofilm
      is always present in intubated patients whatever the duration of intubation and
      appears quickly after intubation. Even after soft rinse, a small but measurable
      part of biofilm remains always present, and seems strongly adherent to the ETT
      lumen. It contains potentially pathogenic bacteria for the lung.

PMID- 25371400
TI  - Use of High-Flow Nasal Cannula Oxygen Therapy in Subjects With ARDS: A 1-Year
      Observational Study.
AB  - BACKGROUND: Beneficial effects of high-flow nasal cannula (HFNC) oxygen on
      oxygenation and respiratory parameters have been reported in a small number of
      subjects with acute respiratory failure (ARF). We aimed to evaluate its effect in
      subjects with ARDS. METHODS: This was an observational single-center study.
      Prospectively obtained data were retrospectively analyzed. All patients admitted
      over 1 y to a university hospital medicosurgical ICU were included.
      Classification was according to the highest ventilatory support required. HFNC
      indications were reviewed, and demographics, clinical characteristics, and course
      of subjects with ARDS according to intubation need were compared. RESULTS: Of 607
      subjects admitted, 560 required ventilatory or oxygen support, among whom 180
      received noninvasive ventilatory support. HFNC was used in 87 subjects and as
      first-line treatment in 51 subjects (29% of first-line noninvasively treated
      subjects), 45 of which had ARDS (PaO2 /FIO2 of 137 mm Hg; 22 men, 57.9 y of age).
      Pneumonia accounted for 82% of ARDS causes. The intubation rate in these subjects
      was 40%. Higher Simplified Acute Physiology Score II (SAPS II; 46 vs 29, P=.001),
      occurrence of additional organ failure (76% vs 26%, P=.002), mainly hemodynamic
      (50% vs 7%, P=.001) or neurological (22% vs 0, P=.01), and trends toward lower
      PaO2 /FIO2 and higher breathing frequency after HFNC initiation were evidenced in
      subjects who failed HFNC. Higher SAPS II scores were associated with HFNC failure
      in multivariate analysis. CONCLUSIONS: In daily care, over one fourth of subjects
      requiring noninvasive ventilatory support were treated via HFNC, with a high
      success rate in subjects with severe ARDS. We conclude that HFNC may be
      considered as first-line therapy in ARF, including patients with ARDS.

PMID- 25371401
TI  - Simulation of late inspiratory rise in airway pressure during pressure support
      ventilation.
AB  - BACKGROUND: Late inspiratory rise in airway pressure (LIRAP, Paw/DeltaT) caused
      by inspiratory muscle relaxation or expiratory muscle contraction is frequently
      seen during pressure support ventilation (PSV), although the modulating factors
      are unknown. METHODS: We investigated the effects of respiratory mechanics
      (normal, obstructive, restrictive, or mixed), inspiratory effort (-2, -8, or -15
      cm H2O), flow cycle criteria (5-40% peak inspiratory flow), and duration of
      inspiratory muscle relaxation (0.18-0.3 s) on LIRAP during PSV using a lung
      simulator and 4 types of ventilators. RESULTS: LIRAP occurred with all lung
      models when inspiratory effort was medium to high and duration of inspiratory
      muscle relaxation was short. The normal lung model was associated with the
      fastest LIRAP, whereas the obstructive lung model was associated with the
      slowest. Unless lung mechanics were normal or mixed, LIRAP was unlikely to occur
      when inspiratory effort was low. Different ventilators were also associated with
      differences in LIRAP speed. Except for within the restrictive lung model, changes
      in flow cycle level did not abolish LIRAP if inspiratory effort was medium to
      high. Increased duration of inspiratory relaxation also led to the elimination of
      LIRAP. Simulation of expiratory muscle contraction revealed that LIRAP occurred
      only when expiratory muscle contraction occurred sometime after the beginning of
      inspiration. CONCLUSIONS: Our simulation study reveals that both respiratory
      resistance and compliance may affect LIRAP. Except for under restrictive lung
      conditions, LIRAP is unlikely to be abolished by simply lowering flow cycle
      criteria when inspiratory effort is strong and relaxation time is rapid. LIRAP
      may be caused by expiratory muscle contraction when it occurs during inspiration.

PMID- 25371402
TI  - A COPD health management program in a community-based primary care setting: a
      randomized controlled trial.
AB  - BACKGROUND: A number of effective strategies have been developed to improve the
      quality of life in patients with COPD. However, few have been implemented in
      patients with COPD at all stages in a community setting. This study evaluated the
      efficacy of a complex COPD health management intervention in rural communities in
      China. METHODS: A randomized controlled trial including 8,217 subjects with COPD
      was implemented from May 2008 to May 2012 in 14 community health-care centers.
      The control group of subjects received usual care, whereas the management group
      of subjects participated in a health management program that included assessing
      the subjects' health status, giving regular health lectures, smoking cessation
      counseling, encouraging regular exercise, providing rehabilitative training and
      psychological counseling, and regular follow-up. As a primary outcome, we
      examined the changes in the BODE index. Secondary outcomes included depression
      and anxiety rates, current smoking rate, awareness of COPD, mortality, risk
      factors, respiratory medication use, hospital admissions, and emergency
      department visits. RESULTS: After 4 y, the mean cumulative value of the BODE
      index increased by 0.7 per subject in the control group and decreased by 0.4 per
      subject in the health management group (difference of 1.1, 95% CI 0.2-2.0, P <
      .001). Health management reduced anxiety symptoms by 4.8%, depression symptoms by
      6.6%, current smoking by 14.3%, mortality due to all causes by 9.0%,
      hospitalizations due to all causes by 16.1%, and emergency department visits due
      to all causes by 18.1% (P < .05 for all). However, it increased immunomodulator
      use by 58.9%, respiratory medication use by 14.1-21.9%, and awareness scores for
      COPD by 57.2% (P < .05 for all). CONCLUSIONS: The health management program is an
      effective community-based strategy for the prevention and management of COPD in
      China, increasing awareness and knowledge among patients and practitioners and
      improving management within the limitations of access to pharmacotherapy.

PMID- 25371403
TI  - Mendelian randomisation meta-analysis sheds doubt on protective associations
      between 'moderate' alcohol consumption and coronary heart disease.

PMID- 25371404
TI  - Leaders must act now to prevent irreversible effects of climate change, say
      scientists.

PMID- 25371405
TI  - Screening psoriatic arthritis tools: analysis of the Early Arthritis for
      Psoriatic Patients questionnaire.

PMID- 25371406
TI  - Lack of utility of SDHB mutation testing in  adrenergic metastatic
      phaeochromocytoma.
AB  - OBJECTIVE: Testing for succinate dehydrogenase subunit B (SDHB) mutations is
      recommended in all patients with metastatic phaeochromocytomas and paragangliomas
      (PPGLs), but may not be required when metastatic disease is accompanied by
      adrenaline production. This retrospective cohort study aimed to establish the
      prevalence of SDHB mutations among patients with metastatic PPGLs, characterised
      by production of adrenaline compared with those without production of adrenaline,
      and to establish genotype-phenotype features of metastatic PPGLs according to
      underlying gene mutations. DESIGN AND METHODS: Presence of SDHB mutations or
      deletions was tested in 205 patients (114 males) aged 42+/-16 years (range 9-86
      years) at diagnosis of metastatic PPGLs with and without adrenaline production.
      RESULTS: Twenty-three of the 205 patients (11%) with metastatic PPGLs had disease
      characterised by production of adrenaline, as defined by increased plasma
      concentrations of metanephrine larger than 5% of the combined increase in both
      normetanephrine and metanephrine. None of these 23 patients had SDHB mutations.
      Of the other 182 patients with no tumoural adrenaline production, 51% had SDHB
      mutations. Metastases in bone were 36-41% more prevalent among patients with SDHB
      mutations or extra-adrenal primary tumours than those without mutations or with
      adrenal primary tumours. Liver metastases were 81% more prevalent among patients
      with adrenal than extra-adrenal primary tumours. CONCLUSION: SDHB mutation
      testing has no utility among patients with adrenaline-producing metastatic PPGLs,
      but is indicated in other patients with metastatic disease. Our study also
      reveals novel associations of metastatic spread with primary tumour location and
      presence of SDHB mutations.

PMID- 25371408
TI  - The Mersey Burns App: evolving a model of validation.
AB  - INTRODUCTION: 'Mersey Burns App' is a smartphone/tablet application that aids in
      the assessment of total burn surface area (TBSA) and calculation of fluid
      resuscitation protocols in burns. This paper presents two studies assessing the
      speed and accuracy of calculations using Mersey Burns (App) in comparison with a
      Lund and Browder chart (paper) when a burn is assessed by medical students and
      clinicians. METHODS: The first study compared the speed and accuracy of TBSA and
      resuscitation calculation for a photograph of a burn with App and paper using
      burns and plastics and emergency medicine trainees and consultants. Developing on
      some of the feedback and results of that study, a second study was then carried
      out using burns-naive medical students assessing a fully simulated burn with both
      modalities. Preference and ease of use of each modality were assessed
      anonymously. RESULTS: The clinician study showed a lower variance in TBSA and
      fluid calculations using the App (p<0.05). The student study showed no difference
      in mean TBSA estimations (p=0.7). Mean time to completion of calculations was
      faster and calculations were more likely to be correct with the App (p<0.001).
      Students favoured the App in the following categories: preference in emergency
      setting, confidence in output, accuracy, speed, ease of calculation, overall use
      and shading (p<0.0001). CONCLUSIONS: Mersey Burns App can facilitate quicker and
      more accurate calculations than Lund and Browder charts. Students also preferred
      the App. This suggests a useful role for the App in the care of patients with
      burns by inexperienced staff.

PMID- 25371407
TI  - Identification of Cdk targets that control cytokinesis.
AB  - The final event of the eukaryotic cell cycle is cytokinesis, when two new
      daughter cells are born. How the timing and execution of cytokinesis is
      controlled is poorly understood. Here, we show that downregulation of cyclin
      dependent kinase (Cdk) activity, together with upregulation of its counteracting
      phosphatase Cdc14, controls each of the sequential steps of cytokinesis,
      including furrow ingression, membrane resolution and cell separation in budding
      yeast. We use phosphoproteome analysis of mitotic exit to identify Cdk targets
      that are dephosphorylated at the time of cytokinesis. We then apply a new and
      widely applicable tool to generate conditionally phosphorylated proteins to
      identify those whose dephosphorylation is required for cytokinesis. This approach
      identifies Aip1, Ede1 and Inn1 as cytokinetic regulators. Our results suggest
      that cytokinesis is coordinately controlled by the master cell cycle regulator
      Cdk together with its counteracting phosphatase and that it is executed by
      concerted dephosphorylation of Cdk targets involved in several cell biological
      processes. 

PMID- 25371409
TI  - Four-in-one antibodies have superior cancer inhibitory activity against EGFR,
      HER2, HER3, and VEGF through disruption of HER/MET crosstalk.
AB  - The anti-HER receptor antibodies cetuximab, trastuzumab, and pertuzumab are used
      widely in clinic to treat metastatic cancer. However, activation of the extensive
      crosstalk among the HER receptors as well as other RTKs, particularly HER-MET
      crosstalk, has emerged as a likely source of drug resistance. In this study, we
      developed two new types of tetra-specific antibodies that recognize EGFR, HER2,
      HER3, and VEGF. These tetra-specific antibodies, termed FL518 (four-in-one
      antibody) and CRTB6 (tetra-specific, tetravalent antibody), not only inhibited
      signaling mediated by these receptors in vitro and in vivo but unexpectedly also
      disrupted HER-MET crosstalk. When compared with two-in-one antibodies and a
      series of bispecific antibodies in multiple tumor models, FL518 and CRTB6 were
      more broadly efficacious. We further showed that tetra-specific antibodies were
      far more effective than bispecific antibodies in inhibiting the growth of anti
      HER-resistant cancer cells, which exhibited elevated levels of MET activation
      both in vitro and in vivo. Overall, our results establish a new principle to
      achieve combined HER inhibition and limit drug resistance using a single
      antibody.

PMID- 25371410
TI  - A noninvasive procedure for early-stage discrimination of malignant and
      precancerous vocal fold lesions based on laryngeal dynamics analysis.
AB  - About two thirds of laryngeal cancers originate at the vocal cords. Early-stage
      detection of malignant vocal fold alterations, including a discrimination of
      premalignant lesions, represents a major challenge in laryngology as precancerous
      vocal fold lesions and small carcinomas are difficult to distinguish by means of
      regular endoscopy only. We report a procedure to discriminate between malignant
      and precancerous lesions by measuring the characteristics of vocal fold dynamics
      by means of a computerized analysis of laryngeal high-speed videos. Ten patients
      with squamous cell T1a carcinoma, ten with precancerous lesions with
      hyperkeratosis, and ten subjects without laryngeal disease underwent high-speed
      laryngoscopy yielding 4,000 images per second. By means of wavelet-based
      phonovibrographic analysis, a set of three clinically meaningful vibratory
      measures was extracted from the videos comprising a total number of 15,000 video
      frames. Statistical analysis (ANOVA with post hoc two-sided t tests, P < 0.05)
      revealed that vocal fold dynamics is significantly affected in the presence of
      precancerous lesions and T1a carcinoma. On the basis of the three measures, a
      discriminating pattern was extracted using a support vector machine-learning
      algorithm performing an individual classification in respect to the different
      clinical groups. By applying a leave-one-out cross-validation strategy, we could
      show that the proposed measures discriminate with a very high performance between
      precancerous lesions and T1a carcinoma (sensitivity, 100%; specificity, 100%).
      Although a large-scale study will be necessary to confirm clinical significance,
      the set of vibratory measures derived in this study may be applicable to improve
      the accuracy and reliability of noninvasive diagnostics of vocal fold lesions.

PMID- 25371413
TI  - A genome-wide view of microsatellite instability: old stories of cancer mutations
      revisited with new sequencing technologies.
AB  - Microsatellites are simple tandem repeats that are present at millions of loci in
      the human genome. Microsatellite instability (MSI) refers to DNA slippage events
      on microsatellites that occur frequently in cancer genomes when there is a defect
      in the DNA-mismatch repair system. These somatic mutations can result in
      inactivation of tumor-suppressor genes or disrupt other noncoding regulatory
      sequences, thereby playing a role in carcinogenesis. Here, we will discuss the
      ways in which high-throughput sequencing data can facilitate genome- or exome
      wide discovery and more detailed investigation of MSI events in microsatellite
      unstable cancer genomes. We will address the methodologic aspects of this
      approach and highlight insights from recent analyses of colorectal and
      endometrial cancer genomes from The Cancer Genome Atlas project. These include
      identification of novel MSI targets within and across tumor types and the
      relationship between the likelihood of MSI events to chromatin structure. Given
      the increasing popularity of exome and genome sequencing of cancer genomes, a
      comprehensive characterization of MSI may serve as a valuable marker of cancer
      evolution and aid in a search for therapeutic targets.

PMID- 25371415
TI  - Chimeric antigen receptor T-cell therapy to target hematologic malignancies.
AB  - Several decades of humoral immunotherapy using monoclonal antibodies and cellular
      immunotherapy using hematopoietic cell transplantation have recently culminated
      in a successful merger: the development and clinical application of genetically
      engineered antibody-T cell chimeras. Also known as chimeric antigen receptor T
      cells (CAR T cells), these entities combine the exquisite antigen specificity of
      antibodies with the polyfunctionality and potency of cellular immunity and are a
      prime example of the potential for synthetic biology to treat disease. CAR T
      cells overcome several of the biologic obstacles that have historically hampered
      immunotherapy while providing fundamental mechanistic insights into cellular
      immunology and revealing new challenges in genetic engineering and target
      selection. Results from early-phase CAR T-cell-based clinical trials demonstrate
      the significant potential for this approach to affect dramatic and complete
      clinical responses while revealing novel toxicities associated with activation of
      potent and specific antitumor immunity.

PMID- 25371412
TI  - Genetic evidence of a precisely tuned dysregulation in the hypoxia signaling
      pathway during oncogenesis.
AB  - The classic model of tumor suppression implies that malignant transformation
      requires full "two-hit" inactivation of a tumor-suppressor gene. However, more
      recent work in mice has led to the proposal of a "continuum" model that involves
      more fluid concepts such as gene dosage-sensitivity and tissue specificity.
      Mutations in the tumor-suppressor gene von Hippel-Lindau (VHL) are associated
      with a complex spectrum of conditions. Homozygotes or compound heterozygotes for
      the R200W germline mutation in VHL have Chuvash polycythemia, whereas
      heterozygous carriers are free of disease. Individuals with classic, heterozygous
      VHL mutations have VHL disease and are at high risk of multiple tumors (e.g., CNS
      hemangioblastomas, pheochromocytoma, and renal cell carcinoma). We report here an
      atypical family bearing two VHL gene mutations in cis (R200W and R161Q), together
      with phenotypic analysis, structural modeling, functional, and transcriptomic
      studies of these mutants in comparison with classical mutants involved in the
      different VHL phenotypes. We demonstrate that the complex pattern of disease
      manifestations observed in VHL syndrome is perfectly correlated with a gradient
      of VHL protein (pVHL) dysfunction in hypoxia signaling pathways. Thus, by
      studying naturally occurring familial mutations, our work validates in humans the
      "continuum" model of tumor suppression.

PMID- 25371416
TI  - Association of the vitamin D binding protein polymorphisms with the risk of type
      2 diabetes mellitus: a meta-analysis.
AB  - OBJECTIVE: Previous studies on the association between vitamin D binding protein
      (DBP) polymorphisms and the risk of type 2 diabetes mellitus (T2DM) have produced
      conflicting results. The purpose of this meta-analysis was to examine whether DBP
      polymorphisms are associated with the risk of T2DM. DESIGN: Systematic review and
      meta-analysis. METHODS: All eligible studies were searched and acquired from the
      Cochrane, Pubmed, ISI, CNKI (Chinese) and Wanfang (Chinese) databases. ORs with
      corresponding 95% CIs were computed to estimate the association between DBP
      polymorphisms and T2DM. In addition, heterogeneity test, meta-regression and
      sensitivity analysis were also conducted. RESULTS: Six studies, which included
      1191 cases and 882 controls, met the inclusion criteria and were included in the
      meta-analysis. The results showed that no significant associations were found
      between codon 416 and codon 420 polymorphisms in the DBP and the risk of T2DM in
      the overall analyses. In stratified analysis, significant associations between
      the codon 420 polymorphism and T2DM were found in Asians (allele Lys vs Thr: OR
      (95% CI) 1.49 (1.19 to 1.85), genotype Lys/Thr versus Thr/Thr: OR (95% CI) 1.80
      (1.36 to 2.38), and Lys/Thr+Lys/Lys versus Thr/Thr: OR (95% CI) 1.81 (1.37 to
      2.39), respectively) but not in Caucasians. For the codon 416, the significant
      association with T2DM was also detected in Asians (genotype Glu/Asp+Glu/Glu vs
      Asp/Asp: OR (95% CI) 1.36 (1.04 to 1.78)) but not in Caucasians. CONCLUSIONS:
      This meta-analysis demonstrated that the DBP polymorphism was moderately
      associated with increased susceptibility to T2DM in Asians, but a similar
      association was not found in Caucasians. It suggested that ethnicity might be the
      potential factor associated with heterogeneity.

PMID- 25371417
TI  - Nodding syndrome in Kitgum District, Uganda: association with conflict and
      internal displacement.
AB  - OBJECTIVES: To test for any temporal association of Nodding syndrome with wartime
      conflict, casualties and household displacement in Kitgum District, northern
      Uganda. METHODS: Data were obtained from publicly available information reported
      by the Ugandan Ministry of Health (MOH), the Armed Conflict Location & Event Data
      (ACLED) Project of the University of Sussex in the UK, peer-reviewed publications
      in professional journals and other sources. RESULTS: Reports of Nodding syndrome
      began to appear in 1997, with the first recorded cases in Kitgum District in
      1998. Cases rapidly increased annually beginning in 2001, with peaks in 2003-2005
      and 2008, 5-6 years after peaks in the number of wartime conflicts and deaths.
      Additionally, peaks of Nodding syndrome cases followed peak influxes 5-7 years
      earlier of households into internal displacement camps. CONCLUSIONS: Peaks of
      Nodding syndrome reported by the MOH are associated with, but temporally
      displaced from, peaks of wartime conflicts, deaths and household internment,
      where infectious disease was rampant and food insecurity rife.

PMID- 25371418
TI  - Seeking the source of Pseudomonas aeruginosa infections in a recently opened
      hospital: an observational study using whole-genome sequencing.
AB  - OBJECTIVES: Pseudomonas aeruginosa is a common nosocomial pathogen responsible
      for significant morbidity and mortality internationally. Patients may become
      colonised or infected with P. aeruginosa after exposure to contaminated sources
      within the hospital environment. The aim of this study was to determine whether
      whole-genome sequencing (WGS) can be used to determine the source in a cohort of
      burns patients at high risk of P. aeruginosa acquisition. STUDY DESIGN: An
      observational prospective cohort study. SETTING: Burns care ward and critical
      care ward in the UK. PARTICIPANTS: Patients with >7% total burns by surface area
      were recruited into the study. METHODS: All patients were screened for P.
      aeruginosa on admission and samples taken from their immediate environment,
      including water. Screening patients who subsequently developed a positive P.
      aeruginosa microbiology result were subject to enhanced environmental
      surveillance. All isolates of P. aeruginosa were genome sequenced. Sequence
      analysis looked at similarity and relatedness between isolates. RESULTS: WGS for
      141 P. aeruginosa isolates were obtained from patients, hospital water and the
      ward environment. Phylogenetic analysis revealed eight distinct clades, with a
      single clade representing the majority of environmental isolates in the burns
      unit. Isolates from three patients had identical genotypes compared with water
      isolates from the same room. There was clear clustering of water isolates by room
      and outlet, allowing the source of acquisitions to be unambiguously identified.
      Whole-genome shotgun sequencing of biofilm DNA extracted from a thermostatic
      mixer valve revealed this was the source of a P. aeruginosa subpopulation
      previously detected in water. In the remaining two cases there was no clear link
      to the hospital environment. CONCLUSIONS: This study reveals that WGS can be used
      for source tracking of P. aeruginosa in a hospital setting, and that acquisitions
      can be traced to a specific source within a hospital ward.

PMID- 25371419
TI  - Estimating the incidence, prevalence and true cost of asthma in the UK: secondary
      analysis of national stand-alone and linked databases in England, Northern
      Ireland, Scotland and Wales-a study protocol.
AB  - INTRODUCTION: Asthma is now one of the most common long-term conditions in the
      UK. It is therefore important to develop a comprehensive appreciation of the
      healthcare and societal costs in order to inform decisions on care provision and
      planning. We plan to build on our earlier estimates of national prevalence and
      costs from asthma by filling the data gaps previously identified in relation to
      healthcare and broadening the field of enquiry to include societal costs. This
      work will provide the first UK-wide estimates of the costs of asthma. In the
      context of asthma for the UK and its member countries (ie, England, Northern
      Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of
      estimates of incidence, prevalence and healthcare utilisation; (2) estimate
      health and societal costs; (3) identify any remaining information gaps and
      explore the feasibility of filling these and (4) provide insights into future
      research that has the potential to inform changes in policy leading to the
      provision of more cost-effective care. METHODS AND ANALYSIS: Secondary analyses
      of data from national health surveys, primary care, prescribing, emergency care,
      hospital, mortality and administrative data sources will be undertaken to
      estimate prevalence, healthcare utilisation and outcomes from asthma. Data
      linkages and economic modelling will be undertaken in an attempt to populate data
      gaps and estimate costs. Separate prevalence and cost estimates will be
      calculated for each of the UK-member countries and these will then be aggregated
      to generate UK-wide estimates. ETHICS AND DISSEMINATION: Approvals have been
      obtained from the NHS Scotland Information Services Division's Privacy Advisory
      Committee, the Secure Anonymised Information Linkage Collaboration Review System,
      the NHS South-East Scotland Research Ethics Service and The University of
      Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We
      will produce a report for Asthma-UK, submit papers to peer-reviewed journals and
      construct an interactive map.

PMID- 25371420
TI  - Incidence of curable sexually transmissible infections among adolescents and
      young adults in remote Australian Aboriginal communities: analysis of
      longitudinal clinical service data.
AB  - OBJECTIVES: To undertake the first comprehensive analysis of the incidence of
      three curable sexually transmissible infections (STIs) within remote Australian
      Aboriginal populations and provide a basis for developing new control
      initiatives. METHODS: We obtained all results for Chlamydia trachomatis (CT),
      Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) testing conducted
      during 2009-2011 in individuals aged >=16 years attending 65 primary health
      services across central and northern Australia. Baseline prevalence and incidence
      of all three infections was calculated by sex and age group. RESULTS: A total of
      17 849 individuals were tested over 35 months. Baseline prevalence was 11.1%,
      9.5% and 17.6% for CT, NG and TV, respectively. During the study period, 7171,
      7439 and 4946 initially negative individuals had a repeat test for CT, NG and TV,
      respectively; these were followed for 6852, 6981 and 6621 person-years and 651
      CT, 609 NG and 486 TV incident cases were detected. Incidence of all three STIs
      was highest in 16-year-olds to 19-year-olds compared with 35+ year olds (incident
      rate ratio: CT 10.9; NG 11.9; TV 2.5). In the youngest age group there were 23.4
      new CT infections per 100 person-years for men and 29.2 for women; and 26.1 and
      23.4 new NG infections per 100 person-years in men and women, respectively. TV
      incidence in this age group for women was also high, at 19.8 per 100 person-years
      but was much lower in men at 3.6 per 100 person-years. CONCLUSIONS: This study,
      the largest ever reported on the age and sex specific incidence of any one of
      these three curable infections, has identified extremely high rates of new
      infection in young people. Sexual health is a priority for remote communities,
      but will clearly need new approaches, at least intensification of existing
      approaches, if a reduction in rates is to be achieved.

PMID- 25371421
TI  - Factors associated with recent previous HIV testing among a sample of recently
      HIV-diagnosed gay men in Australia: a cross-sectional study.
AB  - OBJECTIVE: Timely HIV testing among recently HIV-infected gay men may enable
      earlier access to clinical care and changes in behaviour that will reduce onward
      transmission. We investigated the testing practices of men recently diagnosed
      with HIV to identify factors associated with recent testing. METHODS: In an
      online survey of men in Australia recently diagnosed with HIV, participants were
      asked about their HIV testing history, perceived impediments to testing prior to
      diagnosis, motivation for testing at the time of diagnosis and a range of
      demographic and behavioural characteristics. Descriptive statistics were used to
      compare those men who reported recent HIV testing with those men who had not
      tested for HIV in the 12 months before their diagnosis. RESULTS: Of 187 men who
      provided information about their testing history and social connectedness, 6.4%
      were previously untested for HIV, whereas 65.8% had last tested within the 12
      months prior to their diagnosis. Factors associated with having tested more
      recently were being more socially engaged with other gay men (OR 1.34; 95% CI
      1.10 to 1.63; p=0.003) and having greater optimism about HIV health (OR 1.13; 95%
      CI 1.00 to 1.27; p=0.047). In multivariate analysis, only level of social
      engagement with other gay men remained independently associated (adjusted OR
      1.30; 95% CI 1.07 to 1.59; p=0.003). CONCLUSIONS: Gay community plays a key role
      in the response to HIV in Australia. Building a sense of community through
      programmes that support social engagement between gay men may support earlier and
      more frequent testing.

PMID- 25371422
TI  - Screening for alcohol misuse in sexual health clinics.

PMID- 25371427
TI  - Haemodynamic consequences of targeted single- and dual-site right ventricular
      pacing in adults with congenital heart disease undergoing surgical pulmonary
      valve replacement.
AB  - AIMS: The purpose of this study was to create an epicardial electroanatomic map
      of the right ventricle (RV) and then apply post-operative-targeted single- and
      dual-site RV temporary pacing with measurement of haemodynamic parameters.
      Cardiac resynchronization therapy is an established treatment for symptomatic
      left ventricular (LV) dysfunction. In congenital heart disease, RV dysfunction is
      a common cause of morbidity-little is known regarding the potential benefits of
      CRT in this setting. METHODS AND RESULTS: Sixteen adults (age = 32 +/- 8 years; 6
      M, 10 F) with right bundle branch block (RBBB) and repaired tetralogy of Fallot
      (n = 8) or corrected congenital pulmonary stenosis (n = 8) undergoing surgical
      pulmonary valve replacement (PVR) for pulmonary regurgitation underwent
      epicardial RV mapping and haemodynamic assessment of random pacing configurations
      including the site of latest RV activation. The pre-operative pulmonary
      regurgitant fraction was 49 +/- 10%; mean LV end-diastolic volume (EDV) 85 +/- 19
      mL/min/m(2) and RVEDV 183 +/- 89 mL/min/m(2) on cardiac magnetic resonance
      imaging. The mean pre-operative QRS duration is 136 +/- 26 ms. The commonest site
      of latest activation was the RV free wall and DDD pacing here alone or combined
      with RV apical pacing resulted in significant increases in cardiac output (CO)
      vs. AAI pacing (P < 0.01 all measures). DDDRV alternative site pacing
      significantly improved CO by 16% vs. AAI (P = 0.018), and 8.5% vs. DDDRV apical
      pacing (P = 0.02). CONCLUSION: Single-site RV pacing targeted to the region of
      latest activation in patients with RBBB undergoing PVR induces acute improvements
      in haemodynamics and supports the concept of 'RV CRT'. Targeted pacing in such
      patients has therapeutic potential both post-operatively and in the long term.

PMID- 25371428
TI  - Hospitalization rates and associated cost analysis of cardiac resynchronization
      therapy with an implantable defibrillator and quadripolar vs. bipolar left
      ventricular leads: a comparative effectiveness study.
AB  - AIMS: This study compares, from a prospective, observational, non-randomized
      registry, the post-implant hospitalization rates and associated healthcare
      resource utilization of cardiac resynchronization therapy-defibrillator (CRT-D)
      patients with quadripolar (QUAD) vs. bipolar (BIP) left ventricular (LV) leads.
      METHODS AND RESULTS: Between January 2009 and December 2012, 193 consecutive
      patients receiving de novo CRT-D implants with either a QUAD (n = 116) or a BIP
      (n = 77) LV lead were enrolled at implant and followed until July 2013 at a
      single-centre, university hospital. Post-implant hospitalizations related to
      heart failure (HF) or LV lead surgical revision and associated payer costs were
      identified using ICD-9-CM diagnosis and procedure codes. Italian national
      reimbursement rates were determined. Propensity scores were estimated using a
      logistic regression model based upon 11 pre-implant baseline characteristics and
      were used to derive a 1 : 1 matched cohort of QUAD (n = 77) and BIP (n = 77)
      patients. Hospitalization rates for the two groups were compared using negative
      binomial regression and associated payer costs were compared using non-parametric
      bootstrapping (*10 000) and one-sided hypothesis test. Hospitalization rates of
      the QUAD group [0.15/ patient (pt)-year] were lower than those of the BIP group
      (0.32/ pt-year); the incidence rate ratio was 0.46, P = 0.04. The hospitalization
      costs for the QUAD group (434 +/- 128 ?/pt-year) were lower than those for the
      BIP group (1136 +/- 362 ?/pt-year). The average difference was 718 ?/pt-year, P =
      0.016. CONCLUSIONS: In this comparative effectiveness assessment of well-matched
      groups of CRT-D patients with quadripolar and bipolar LV leads, QUAD patients
      experienced a lower rate of hospitalizations for HF and LV lead surgical
      revision, and a lower cost burden. This has important implications for LV pacing
      lead choice.

PMID- 25371429
TI  - Expression profile and gene age jointly shaped the genome-wide distribution of
      premature termination codons in a Drosophila melanogaster population.
AB  - Widespread premature termination codon mutations (PTCs) were recently observed in
      human and fly populations. We took advantage of the population resequencing data
      in the Drosophila Genetic Reference Panel to investigate how the expression
      profile and the evolutionary age of genes shaped the allele frequency
      distribution of PTCs. After generating a high-quality data set of PTCs, we
      clustered genes harboring PTCs into three categories: genes encoding low
      frequency PTCs (<= 1.5%), moderate-frequency PTCs (1.5-10%), and high-frequency
      PTCs (>10%). All three groups show narrow transcription compared with PTC-free
      genes, with the moderate- and high-PTC frequency groups showing a pronounced
      pattern. Moreover, nearly half (42%) of the PTC-encoding genes are not expressed
      in any tissue. Interestingly, the moderate-frequency PTC group is strongly
      enriched for genes expressed in midgut, whereas genes harboring high-frequency
      PTCs tend to have sex-specific expression. We further find that although young
      genes born in the last 60 My compose a mere 9% of the genome, they represent 16%,
      30%, and 50% of the genes containing low-, moderate-, and high-frequency PTCs,
      respectively. Among DNA-based and RNA-based duplicated genes, the child copy is
      approximately twice as likely to contain PTCs as the parent copy, whereas young
      de novo genes are as likely to encode PTCs as DNA-based duplicated new genes.
      Based on these results, we conclude that expression profile and gene age jointly
      shaped the landscape of PTC-mediated gene loss. Therefore, we propose that new
      genes may need a long time to become stably maintained after the origination.

PMID- 25371430
TI  - IQ-TREE: a fast and effective stochastic algorithm for estimating maximum
      likelihood phylogenies.
AB  - Large phylogenomics data sets require fast tree inference methods, especially for
      maximum-likelihood (ML) phylogenies. Fast programs exist, but due to inherent
      heuristics to find optimal trees, it is not clear whether the best tree is found.
      Thus, there is need for additional approaches that employ different search
      strategies to find ML trees and that are at the same time as fast as currently
      available ML programs. We show that a combination of hill-climbing approaches and
      a stochastic perturbation method can be time-efficiently implemented. If we allow
      the same CPU time as RAxML and PhyML, then our software IQ-TREE found higher
      likelihoods between 62.2% and 87.1% of the studied alignments, thus efficiently
      exploring the tree-space. If we use the IQ-TREE stopping rule, RAxML and PhyML
      are faster in 75.7% and 47.1% of the DNA alignments and 42.2% and 100% of the
      protein alignments, respectively. However, the range of obtaining higher
      likelihoods with IQ-TREE improves to 73.3-97.1%. IQ-TREE is freely available at
      http://www.cibiv.at/software/iqtree. 

PMID- 25371431
TI  - A systematic survey of an intragenic epistatic landscape.
AB  - Mutations are the source of evolutionary variation. The interactions of multiple
      mutations can have important effects on fitness and evolutionary trajectories. We
      have recently described the distribution of fitness effects of all single
      mutations for a nine-amino-acid region of yeast Hsp90 (Hsp82) implicated in
      substrate binding. Here, we report and discuss the distribution of intragenic
      epistatic effects within this region in seven Hsp90 point mutant backgrounds of
      neutral to slightly deleterious effect, resulting in an analysis of more than
      1,000 double mutants. We find negative epistasis between substitutions to be
      common, and positive epistasis to be rare--resulting in a pattern that indicates
      a drastic change in the distribution of fitness effects one step away from the
      wild type. This can be well explained by a concave relationship between phenotype
      and genotype (i.e., a concave shape of the local fitness landscape), suggesting
      mutational robustness intrinsic to the local sequence space. Structural analyses
      indicate that, in this region, epistatic effects are most pronounced when a
      solvent-inaccessible position is involved in the interaction. In contrast, all 18
      observations of positive epistasis involved at least one mutation at a solvent
      exposed position. By combining the analysis of evolutionary and biophysical
      properties of an epistatic landscape, these results contribute to a more detailed
      understanding of the complexity of protein evolution.

PMID- 25371432
TI  - Estimation of the spontaneous mutation rate in Heliconius melpomene.
AB  - We estimated the spontaneous mutation rate in Heliconius melpomene by genome
      sequencing of a pair of parents and 30 of their offspring, based on the ratio of
      number of de novo heterozygotes to the number of callable site-individuals. We
      detected nine new mutations, each one affecting a single site in a single
      offspring. This yields an estimated mutation rate of 2.9 * 10(-9) (95% confidence
      interval, 1.3 * 10(-9)-5.5 * 10(-9)), which is similar to recent estimates in
      Drosophila melanogaster, the only other insect species in which the mutation rate
      has been directly estimated. We infer that recent effective population size of H.
      melpomene is about 2 million, a substantially lower value than its census size,
      suggesting a role for natural selection reducing diversity. We estimate that H.
      melpomene diverged from its Mullerian comimic H. erato about 6 Ma, a somewhat
      later date than estimates based on a local molecular clock. 

PMID- 25371433
TI  - Transcriptomic evidence for the evolution of shoot meristem function in
      sporophyte-dominant land plants through concerted selection of ancestral
      gametophytic and sporophytic genetic programs.
AB  - Alternation of generations, in which the haploid and diploid stages of the life
      cycle are each represented by multicellular forms that differ in their
      morphology, is a defining feature of the land plants (embryophytes). Anciently
      derived lineages of embryophytes grow predominately in the haploid gametophytic
      generation from apical cells that give rise to the photosynthetic body of the
      plant. More recently evolved plant lineages have multicellular shoot apical
      meristems (SAMs), and photosynthetic shoot development is restricted to the
      sporophyte generation. The molecular genetic basis for this evolutionary shift
      from gametophyte-dominant to sporophyte-dominant life cycles remains a major
      question in the study of land plant evolution. We used laser microdissection and
      next generation RNA sequencing to address whether angiosperm meristem patterning
      genes expressed in the sporophytic SAM of Zea mays are expressed in the
      gametophytic apical cells, or in the determinate sporophytes, of the model
      bryophytes Marchantia polymorpha and Physcomitrella patens. A wealth of
      upregulated genes involved in stem cell maintenance and organogenesis are
      identified in the maize SAM and in both the gametophytic apical cell and
      sporophyte of moss, but not in Marchantia. Significantly, meiosis-specific
      genetic programs are expressed in bryophyte sporophytes, long before the onset of
      sporogenesis. Our data suggest that this upregulated accumulation of meiotic gene
      transcripts suppresses indeterminate cell fate in the Physcomitrella sporophyte,
      and overrides the observed accumulation of meristem patterning genes. A model for
      the evolution of indeterminate growth in the sporophytic generation through the
      concerted selection of ancestral meristem gene programs from gametophyte-dominant
      lineages is proposed. 

PMID- 25371434
TI  - Opsin clines in butterflies suggest novel roles for insect photopigments.
AB  - Opsins are ancient molecules that enable animal vision by coupling to a vitamin
      derived chromophore to form light-sensitive photopigments. The primary drivers of
      evolutionary diversification in opsins are thought to be visual tasks related to
      spectral sensitivity and color vision. Typically, only a few opsin amino acid
      sites affect photopigment spectral sensitivity. We show that opsin genes of the
      North American butterfly Limenitis arthemis have diversified along a latitudinal
      cline, consistent with natural selection due to environmental factors. We
      sequenced single nucleotide (SNP) polymorphisms in the coding regions of the
      ultraviolet (UVRh), blue (BRh), and long-wavelength (LWRh) opsin genes from ten
      butterfly populations along the eastern United States and found that a majority
      of opsin SNPs showed significant clinal variation. Outlier detection and analysis
      of molecular variance indicated that many SNPs are under balancing selection and
      show significant population structure. This contrasts with what we found by
      analysing SNPs in the wingless and EF-1 alpha loci, and from neutral amplified
      fragment length polymorphisms, which show no evidence of significant locus
      specific or genome-wide structure among populations. Using a combination of
      functional genetic and physiological approaches, including expression in cell
      culture, transgenic Drosophila, UV-visible spectroscopy, and optophysiology, we
      show that key BRh opsin SNPs that vary clinally have almost no effect on spectral
      sensitivity. Our results suggest that opsin diversification in this butterfly is
      more consistent with natural selection unrelated to spectral tuning. Some of the
      clinally varying SNPs may instead play a role in regulating opsin gene expression
      levels or the thermostability of the opsin protein. Lastly, we discuss the
      possibility that insect opsins might have important, yet-to-be elucidated,
      adaptive functions in mediating animal responses to abiotic factors, such as
      temperature or photoperiod. 

PMID- 25371436
TI  - Ecological transition predictably associated with gene degeneration.
AB  - Gene degeneration or loss can significantly contribute to phenotypic
      diversification, but may generate genetic constraints on future evolutionary
      trajectories, potentially restricting phenotypic reversal. Such constraints may
      manifest as directional evolutionary trends when parallel phenotypic shifts
      consistently involve gene degeneration or loss. Here, we demonstrate that
      widespread parallel evolution in Penstemon from blue to red flowers predictably
      involves the functional inactivation and degeneration of the enzyme flavonoid
      3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the
      production of blue floral pigments. Other types of genetic mutations do not
      consistently accompany this phenotypic shift. This pattern may be driven by the
      relatively large mutational target size of degenerative mutations to this locus
      and the apparent lack of associated pleiotropic effects. The consistent
      degeneration of F3'5'H may provide a mechanistic explanation for the observed
      asymmetry in the direction of flower color evolution in Penstemon: Blue to red
      transitions are common, but reverse transitions have not been observed. Although
      phenotypic shifts in this system are likely driven by natural selection, internal
      constraints may generate predictable genetic outcomes and may restrict future
      evolutionary trajectories. 

PMID- 25371435
TI  - Toward more accurate ancestral protein genotype-phenotype reconstructions with
      the use of species tree-aware gene trees.
AB  - The resurrection of ancestral proteins provides direct insight into how natural
      selection has shaped proteins found in nature. By tracing substitutions along a
      gene phylogeny, ancestral proteins can be reconstructed in silico and
      subsequently synthesized in vitro. This elegant strategy reveals the complex
      mechanisms responsible for the evolution of protein functions and structures.
      However, to date, all protein resurrection studies have used simplistic
      approaches for ancestral sequence reconstruction (ASR), including the assumption
      that a single sequence alignment alone is sufficient to accurately reconstruct
      the history of the gene family. The impact of such shortcuts on conclusions about
      ancestral functions has not been investigated. Here, we show with simulations
      that utilizing information on species history using a model that accounts for the
      duplication, horizontal transfer, and loss (DTL) of genes statistically increases
      ASR accuracy. This underscores the importance of the tree topology in the
      inference of putative ancestors. We validate our in silico predictions using in
      vitro resurrection of the LeuB enzyme for the ancestor of the Firmicutes, a major
      and ancient bacterial phylum. With this particular protein, our experimental
      results demonstrate that information on the species phylogeny results in a
      biochemically more realistic and kinetically more stable ancestral protein.
      Additional resurrection experiments with different proteins are necessary to
      statistically quantify the impact of using species tree-aware gene trees on
      ancestral protein phenotypes. Nonetheless, our results suggest the need for
      incorporating both sequence and DTL information in future studies of protein
      resurrections to accurately define the genotype-phenotype space in which proteins
      diversify. 

PMID- 25371438
TI  - Intraosseous meningioma mimicking a metastasis.

PMID- 25371437
TI  - Sinobronchial allergic aspergillosis with allergic bronchopulmonary
      aspergillosis: a less common co-existence.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary
      disorder that is characterised by a hyper-responsiveness of the airways to
      Aspergillus fumigatus. Although several other fungi may also present with similar
      clinical conditions, Aspergillus remains the most common fungal pathogen causing
      airway infections. Co-existence of ABPA with allergic Aspergillus sinusitis (AAS)
      is an uncommon presentation. The concept of one airway/one disease justifies the
      co-existence of ABPA with AAS, but it does not always hold true. We report a case
      of a 35-year-old woman who presented with symptoms suggestive of bronchial
      asthma. On further investigation, the radiological pattern showed fleeting
      shadows and CT scan showed central cystic bronchiectatic changes characteristic
      of ABPA. The nasal secretions were investigated for the presence of Aspergillus
      and were found to be positive. Hence a diagnosis of ABPA with AAS was
      established. The patient was treated with oral steroids and antifungal drugs. 

PMID- 25371439
TI  - Biomechanical analysis of subpectoral biceps tenodesis: effect of screw
      malpositioning on proximal humeral strength.
AB  - BACKGROUND: Humeral fracture after subpectoral tenodesis of the long head of
      biceps tendon (LHB) is a rare but devastating complication. PURPOSE: To determine
      whether malpositioned (laterally eccentric) tenodesis screw placement has an
      influence on humerus strength reduction compared with central placement. STUDY
      DESIGN: Controlled laboratory study. METHODS: Two groups, each consisting of 10
      matched pairs of human humeri, were used for this study. Biceps tendons were
      fixed subpectorally with 8-mm screws in unicortical 8-mm sockets. In the first
      group, the socket was placed concentrically in the bicipital groove and the
      tendon was fixed with an interference screw. In the second group, the socket was
      malpositioned 30% eccentrically to the lateral (tension) side of the humerus.
      Contralateral humeri remained intact as positive controls. Specimens were aligned
      in 40 degrees  of abduction, and a uniaxial compressive force was applied to the
      humeral head until failure. Strength reduction was reported as percentage
      reduction in ultimate failure load between paired humeri. Relative defect size
      was calculated as a percentage of the total humeral width at the height of the
      tenodesis. RESULTS: Laterally eccentric malpositioned biceps tenodeses
      significantly decreased humeral strength compared with intact (mean change, -25%;
      SD, 23%; P=.017), while concentrically placed biceps tenodeses did not (mean
      change, -10%; SD, 15%; P=.059). A linear regression between relative defect size
      and strength reduction in the malpositioned group showed a significant negative
      linear correlation (beta=-2.577; R2=0.423; P=.042). CONCLUSION: Humeral fracture
      after subpectoral tenodesis of the LHB is a complication that may be minimized
      with careful surgical technique. Laterally eccentric malpositioned biceps
      tenodesis caused significant reduction (25%) in humeral strength, which might be
      clinically relevant and contribute to postsurgical humeral shaft fracture.
      Strength reduction was also significantly correlated with relative defect size.
      Surgeons using this technique should ensure central and orthogonal placement of
      the socket, especially in smaller individuals. This study lends biomechanical
      evidence to support the clinical procedure of a correctly, concentrically placed
      tenodesis screw. CLINICAL RELEVANCE: These biomechanical results indicate that in
      a clinical setting, special attention should be drawn to patient selection for
      LHB tenodesis. This study reveals that central screw positioning is critical,
      particularly in high-impact and overhead athletes, as well as for patients with
      small humeral widths or osteoporotic bone quality. Alternative surgical options
      such as smaller screws or other fixation methods might be considered to diminish
      the postoperative risk of humeral fracture.

PMID- 25371440
TI  - Serum 25-Hydroxyvitamin D Levels and Stress Fractures in Military Personnel: A
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: Low serum 25-hydroxyvitamin D (25(OH)D) levels have been associated
      with stress fractures in various physically active populations such as the
      military. PURPOSE: To examine the association between serum 25(OH)D levels and
      stress fractures in the military. STUDY DESIGN: Systematic review and meta
      analysis. METHODS: Relevant studies were identified through searching multiple
      databases and manually screening reference lists. Two reviewers independently
      selected the included studies by applying the eligibility criteria to the title,
      abstract, and/or full text of the articles yielded in the search. Two reviewers
      also independently conducted the methodological quality assessment and data
      extraction. A random-effects model was used to calculate the mean difference (MD)
      with 95% CI in serum 25(OH)D levels between stress fracture cases and controls.
      RESULTS: Nine observational studies on lower extremity stress fractures were
      eligible, and 1 was excluded due to inadequate data. A total of 2634 military
      personnel (age, 18-30 years; 44% male) with 761 cases (16% male) and 1873
      controls (61% male) from 8 studies were included in the analysis. Three of the 8
      studies measured serum 25(OH)D levels at the time of stress fracture diagnosis,
      and the 5 remaining studies measured serum 25(OH)D levels at the time of entry
      into basic training. The mean serum 25(OH)D level was lower in stress fracture
      cases than in controls at the time of entry into basic training (MD, -2.63 ng/mL;
      95% CI, -5.80 to 0.54; P = .10; I(2) = 65%) and at the time of stress fracture
      diagnosis (MD, -2.26 ng/mL; 95% CI, -3.89 to -0.63; P = .007; I(2) = 42%).
      CONCLUSION: Despite the inherent limitations of the included studies, the study
      results suggest some association between low serum 25(OH)D levels and lower
      extremity stress fractures in military personnel. Given the rigorous training of
      military personnel, implementing strategies to ensure sufficient 25(OH)D levels
      may be beneficial for reducing the risk of stress fractures.

PMID- 25371441
TI  - Endovascular intervention in thoracic surgery.
AB  - There are few reports regarding endovascular treatment in thoracic surgical
      patients. Here, we describe the cases of 2 patients who received adjuvant
      endovascular therapy prior to surgery. One presented with recurrent chest
      infection. Computed tomography revealed systemic blood supply to an intralobar
      sequestration. The other presented with an avulsion injury to the internal
      mammary vein. Coil embolization was employed in both patients with subsequent
      uncomplicated surgery. Endovascular intervention may stop active bleeding in the
      chest and reduce the risk of operative hemorrhage in selected thoracic surgical
      patients. 

PMID- 25371443
TI  - Anti-TNF response rates in radiographic and non-radiographic axial
      spondyloarthropathy.

PMID- 25371444
TI  - Reducing mental illness stigma in health care students and professionals: a
      review of the literature.
AB  - OBJECTIVE: The aim of this study was to examine the effectiveness of
      interventions designed to reduce mental illness stigma among healthcare students
      and professionals. METHOD: A literature search was conducted using the Cochrane
      Library and PubMed. RESULTS: Randomised controlled trial level evidence
      demonstrated that interventions involving direct contact, indirect filmed contact
      or an educational email effectively reduced stigma in the short term. Role play
      was the only intervention with randomised controlled trial level evidence
      demonstrating no effect. There was not enough evidence to suggest that any
      intervention can maintain stigma reduction over time. CONCLUSIONS: Stigma
      reduction in healthcare students and professionals needs to be sustained over
      time if it is to result in positive changes for people living with mental
      illness. Further research is needed to determine which interventions, if any, can
      achieve this. Only then will large-scale implementation of a stigma reduction
      intervention be feasible and beneficial to people living with mental illness.

PMID- 25371442
TI  - Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis
      of autoimmune arthritis.
AB  - OBJECTIVES: Although myeloid-derived suppressor cells (MDSCs) have been linked to
      T cell tolerance, their role in autoimmune rheumatoid arthritis (RA) remains
      elusive. Here we investigate the potential association of MDSCs with the disease
      pathogenesis using a preclinical model of RA and specimen collected from patients
      with RA. METHODS: The frequency of MDSCs in blood, lymphoid tissues, inflamed
      paws or synovial fluid and their association with disease severity, tissue
      inflammation and the levels of pathogenic T helper (Th) 17 cells were examined in
      arthritic mice or in patients with RA (n=35) and osteoarthritis (n=15). The MDSCs
      in arthritic mice were also characterised for their phenotype, inflammation
      status, T cell suppressive activity and their capacity of pro-Th17 cell
      differentiation. The involvement of MDSCs in the disease pathology and a Th17
      response was examined by adoptive transfer or antibody depletion of MDSCs in
      arthritic mice or by coculturing mouse or human MDSCs with naive CD4+ T cells
      under Th17-polarising conditions. RESULTS: MDSCs significantly expanded in
      arthritic mice and in patients with RA, which correlated positively with disease
      severity and an inflammatory Th17 response. While displaying T cell suppressive
      activity, MDSCs from arthritic mice produced high levels of inflammatory
      cytokines (eg, interleukin (IL)-1beta, TNF-alpha). Mouse and human MDSCs promoted
      Th17 cell polarisation ex vivo. Transfer of MDSCs facilitated disease
      progression, whereas their elimination in arthritic mice ameliorated disease
      symptoms concomitant with reduction of IL-17A/Th17 cells. CONCLUSIONS: Our
      studies suggest that proinflammatory MDSCs with their capacity to drive Th17 cell
      differentiation may be a critical pathogenic factor in autoimmune arthritis.

PMID- 25371445
TI  - Association of prostate cancer risk variants with gene expression in normal and
      tumor tissue.
AB  - BACKGROUND: Numerous germline genetic variants are associated with prostate
      cancer risk, but their biologic role is not well understood. One possibility is
      that these variants influence gene expression in prostate tissue. We therefore
      examined the association of prostate cancer risk variants with the expression of
      genes nearby and genome-wide. METHODS: We generated mRNA expression data for
      20,254 genes with the Affymetrix GeneChip Human Gene 1.0 ST microarray from
      normal prostate (N = 160) and prostate tumor (N = 264) tissue from participants
      of the Physicians' Health Study and Health Professionals Follow-up Study. With
      linear models, we tested the association of 39 risk variants with nearby genes
      and all genes, and the association of each variant with canonical pathways using
      a global test. RESULTS: In addition to confirming previously reported
      associations, we detected several new significant (P < 0.05) associations of
      variants with the expression of nearby genes including C2orf43, ITGA6, MLPH,
      CHMP2B, BMPR1B, and MTL5. Genome-wide, five genes (MSMB, NUDT11, RBPMS2, NEFM,
      and KLHL33) were significantly associated after accounting for multiple
      comparisons for each SNP (P < 2.5 * 10(-6)). Many more genes had an FDR <10%,
      including SRD5A1 and PSCA, and we observed significant associations with pathways
      in tumor tissue. CONCLUSIONS: The risk variants were associated with several
      genes, including promising prostate cancer candidates and lipid metabolism
      pathways, suggesting mechanisms for their impact on disease. These genes should
      be further explored in biologic and epidemiologic studies. IMPACT: Determining
      the biologic role of these variants can lead to improved understanding of
      prostate cancer etiology and identify new targets for chemoprevention.

PMID- 25371446
TI  - Recurrent BRCA1 and BRCA2 mutations in Mexican women with breast cancer.
AB  - BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes confer an estimated
      58% to 80% lifetime risk of breast cancer. In general, screening is done for
      cancer patients if a relative has been diagnosed with breast or ovarian cancer.
      There are few data on the prevalence of mutations in these genes in Mexican women
      with breast cancer and this hampers efforts to develop screening policies in
      Mexico. METHODS: We screened 810 unselected women with breast cancer from three
      cities in Mexico (Mexico City, Veracruz, and Monterrey) for mutations in BRCA1
      and BRCA2, including a panel of 26 previously reported mutations. RESULTS: Thirty
      five mutations were identified in 34 women (4.3% of total) including 20 BRCA1
      mutations and 15 BRCA2 mutations. Twenty-two of the 35 mutations were recurrent
      mutations (62.8%). Only five of the 34 mutation carriers had a first-degree
      relative with breast cancer (three with BRCA1 and two with BRCA2 mutations).
      CONCLUSION: These results support the rationale for a strategy of screening for
      recurrent mutations in all women with breast cancer in Mexico, as opposed to
      restricting screening to those with a sister or mother with breast or ovarian
      cancer. IMPACT: These results will impact cancer genetic testing in Mexico and
      the identification of at-risk individuals who will benefit from increased
      surveillance. Cancer Epidemiol Biomarkers Prev; 24(3); 498-505. (c)2014 AACR.

PMID- 25371448
TI  - Temporal stability and determinants of white blood cell DNA methylation in the
      breakthrough generations study.
AB  - BACKGROUND: Epigenome-wide association studies (EWAS) using measurements of blood
      DNA methylation are performed to identify associations of methylation changes
      with environmental and lifestyle exposures and disease risk. However, little is
      known about the variation of methylation markers in the population and their
      stability over time, both important factors in the design and interpretation of
      EWAS. We aimed to identify stable variable methylated probes (VMP), i.e., markers
      that are variable in the population, yet stable over time. METHODS: We estimated
      the intraclass correlation coefficient (ICC) for each probe on the Illumina 450K
      methylation array in paired samples collected approximately 6 years apart from 92
      participants in the Breakthrough Generations Study. We also evaluated
      relationships with age, reproductive and hormonal history, weight, alcohol
      intake, and smoking. RESULTS: Approximately 17% of probes had an ICC > 0.50 and
      were considered stable VMPs (stable-VMPs). Stable-VMPs were enriched for probes
      located in "shores" bordering CpG islands, and at approximately 1.3 kb downstream
      from the transcription start site in the transition between the unmethylated
      promoter and methylated gene body. Both cross-sectional and longitudinal data
      analyses provided strong evidence for associations between changes in methylation
      levels and aging. Smoking-related probes at 2q37.1 and AHRR were stable-VMPs and
      related to time since quitting. We also observed associations between methylation
      and weight changes. CONCLUSION: Our results provide support for the use of white
      blood cell DNA methylation as a biomarker of exposure in EWAS. IMPACT: Larger
      studies, preferably with repeated measures over time, will be required to
      establish associations between specific probes and exposures.

PMID- 25371447
TI  - Endogenous sex hormones and breast density in young women.
AB  - BACKGROUND: Breast density is a strong risk factor for breast cancer and reflects
      epithelial and stromal content. Breast tissue is particularly sensitive to
      hormonal stimuli before it fully differentiates following the first full-term
      pregnancy. Few studies have examined associations between sex hormones and breast
      density among young women. METHODS: We conducted a cross-sectional study among
      180 women ages 25 to 29 years old who participated in the Dietary Intervention
      Study in Children 2006 Follow-up Study. Eighty-five percent of participants
      attended a clinic visit during their luteal phase of menstrual cycle. Magnetic
      resonance imaging measured the percentage of dense breast volume (%DBV), absolute
      dense breast volume (ADBV), and absolute nondense breast volume (ANDBV). Multiple
      linear mixed-effect regression models were used to evaluate the association of
      sex hormones and sex hormone-binding globulin (SHBG) with %DBV, ADBV, and ANDBV.
      RESULTS: Testosterone was significantly positively associated with %DBV and ADBV.
      The multivariable geometric mean of %DBV and ADBV across testosterone quartiles
      increased from 16.5% to 20.3% and from 68.6 to 82.3 cm(3), respectively (Ptrend
      <= 0.03). There was no association of %DBV or ADBV with estrogens, progesterone,
      non-SHBG-bound testosterone, or SHBG (Ptrend >= 0.27). Neither sex hormones nor
      SHBG was associated with ANDBV except progesterone; however, the progesterone
      result was nonsignificant in analysis restricted to women in the luteal phase.
      CONCLUSIONS: These findings suggest a modest positive association between
      testosterone and breast density in young women. IMPACT: Hormonal influences at
      critical periods may contribute to morphologic differences in the breast
      associated with breast cancer risk later in life.

PMID- 25371449
TI  - Factor Structure and Construct Validity of the Parent-Reported Inventory of
      Callous-Unemotional Traits Among High-Risk 9-Year-Olds.
AB  - The presence of callous-unemotional (CU) traits delineates a subgroup of youth
      with severe antisocial behavior. However, debate surrounds the best method to
      assess CU traits. This study examined the factor structure of the parent-reported
      Inventory of Callous-Unemotional Traits (ICU) among high-risk 9-year-olds (N =
      540) and its predictive validity over 1 year. Confirmatory factor analysis showed
      support for a three-factor bifactor model and revised two-factor model using a
      shortened ICU. Within a three-factor bifactor framework the general CU traits
      factor and specific uncaring factor scores were related to higher externalizing
      and lower internalizing behavior problems at ages 9.5 and 10.5. Findings were
      replicated using teacher-reported outcomes. However, results also suggest the
      need for item refinement and highlight the utility of a two-factor solution using
      a shortened ICU. In particular, the meaning of the unemotional items is discussed
      in relation to the conceptualization of CU traits. 

PMID- 25371450
TI  - Differential response profiles in children and adolescents with attention
      deficit/hyperactivity disorder: treatment with atomoxetine.
AB  - Atomoxetine has been shown to be safe and effective in the treatment of attention
      deficit/hyperactivity disorder (ADHD). The purpose of this post hoc analysis was
      to examine response trajectories of pediatric patients treated with atomoxetine.
      Data were pooled from 7 atomoxetine double-blind, placebo-controlled clinical
      trials conducted in pediatric patients between November 1998 and June 2004.
      Growth mixture modeling was applied to the investigator-rated ADHD rating scale
      (ADHDRS-Inv) and Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scores in
      the randomized acute phase (6-9 weeks) to explore whether there were groups of
      patients who differed in their response to atomoxetine. Classification and
      regression tree analyses were performed to identify predictors that can help
      categorize subjects to different response profiles. Patients (N = 925) were
      mostly male (73%) and of the combined subtype (74%). Most patients had a response
      pattern characterized by gradual, modest improvement, while a smaller group
      experienced early, robust improvement. 

PMID- 25371451
TI  - Can we identify and predict failure of knee implants from routine bone density
      measurements?

PMID- 25371452
TI  - Measuring function after hip and knee surgery: the evidence to support
      performance-based functional outcome tasks.
AB  - Accurate, reproducible outcome measures are essential for the evaluation of any
      orthopaedic procedure, in both clinical practice and research. Commonly used
      patient-reported outcome measures (PROMs) have drawbacks such as 'floor' and
      'ceiling' effects, limitations of worldwide adaptability and an inability to
      distinguish pain from function. They are also unable to measure the true outcome
      of an intervention rather than a patient's perception of that outcome.
      Performance-based functional outcome tools may address these problems. It is
      important that both clinicians and researchers are aware of these measures when
      dealing with high-demand patients, using a new intervention or implant, or
      testing a new rehabilitation protocol. This article provides an overview of some
      of the clinically-validated performance-based functional outcome tools used in
      the assessment of patients undergoing hip and knee surgery.

PMID- 25371453
TI  - Classification of failure of limb salvage after reconstructive surgery for bone
      tumours : a modified system Including biological and expandable reconstructions.
AB  - Previous classification systems of failure of limb salvage focused primarily on
      endoprosthetic failures and lacked sufficient depth for the effective study of
      the causes of failure. In order to address these inadequacies, the International
      Society of Limb Salvage (ISOLS) formed a committee to recommend revisions of the
      previous systems. The purpose of this study was to report on their
      recommendations. The modifications were prepared using an earlier, evidence-based
      model with subclassification based on the existing medical literature.
      Subclassification for all five primary types of failure of limb salvage following
      endoprosthetic reconstruction were formulated and a complementary system was
      derived for the failure of biological reconstruction. An additional
      classification of failure in paediatric patients was also described. Limb salvage
      surgery presents a complex array of potential mechanisms of failure, and a
      complete and precise classification of types of failure is required. Earlier
      classification systems lacked specificity, and the evidence-based system outlined
      here is designed to correct these weaknesses and to provide a means of reporting
      failures of limb salvage in order to allow the interpretation of outcome
      following reconstructive surgery.

PMID- 25371454
TI  - Subcapital osteotomy of the femoral neck for patients with healed slipped capital
      femoral epiphysis.
AB  - We report the clinical and radiological outcome of subcapital osteotomy of the
      femoral neck in the management of symptomatic femoroacetabular impingement (FAI)
      resulting from a healed slipped capital femoral epiphysis (SCFE). We believe this
      is only the second such study in the literature. We studied eight patients (eight
      hips) with symptomatic FAI after a moderate to severe healed SCFE. There were six
      male and two female patients, with a mean age of 17.8 years (13 to 29). All
      patients underwent a subcapital intracapsular osteotomy of the femoral neck after
      surgical hip dislocation and creation of an extended retinacular soft-tissue
      flap. The mean follow-up was 41 months (20 to 84). Clinical assessment included
      measurement of range of movement, Harris Hip Score (HHS) and Western Ontario and
      McMaster Universities Osteoarthritis score (WOMAC). Radiological assessment
      included pre- and post-operative calculation of the anterior slip angle (ASA) and
      lateral slip angle (LSA), the anterior offset angle (AOA) and centre head
      trochanteric distance (CTD). The mean HHS at final follow-up was 92.5 (85 to
      100), and the mean WOMAC scores for pain, stiffness and function were 1.3 (0 to
      4), 1.4 (0 to 6) and 3.6 (0 to 19) respectively. There was a statistically
      significant improvement in all the radiological measurements post-operatively.
      The mean ASA improved from 36.6 degrees  (29 degrees  to 44 degrees ) to 10.3
      degrees  (5 degrees  to 17 degrees ) (p < 0.01). The mean LSA improved from 36.6
      degrees  (31 degrees  to 43 degrees ) to 15.4 degrees  (8 degrees  to 21 degrees
      ) (p < 0.01). The mean AOA decreased from 64.4 degrees  (50 degrees  to 78
      degrees ) 32.0 degrees  (25 degrees  to 39 degrees ) post-operatively (p < 0.01).
      The mean CTD improved from -8.2 mm (-13.8 to +3.1) to +2.8 mm (-7.6 to +11.0) (p
      < 0.01). Two patients underwent further surgery for nonunion. No patient suffered
      avascular necrosis of the femoral head. Subcapital osteotomy for patients with a
      healed SCFE is more challenging than subcapital re-orientation in those with an
      acute or sub-acute SCFE and an open physis. An effective correction of the
      deformity, however, can be achieved with relief of symptoms related to
      impingement.

PMID- 25371455
TI  - Cementless total hip replacement without femoral osteotomy in patients with
      severe developmental dysplasia of the hip: minimum 15-year clinical and
      radiological results.
AB  - We describe the clinical and radiological results of cementless primary total hip
      replacement (THR) in 25 patients (18 women and seven men; 30 THRs) with severe
      developmental dysplasia of the hip (DDH). Their mean age at surgery was 47 years
      (23 to 89). In all, 21 hips had Crowe type III dysplasia and nine had Crowe type
      IV. Cementless acetabular components with standard polyethylene liners were
      introduced as close to the level of the true acetabulum as possible. The modular
      cementless S-ROM femoral component was used with a low resection of the femoral
      neck. A total of 21 patients (25 THRs) were available for review at a mean follow
      up of 18.7 years (15.8 to 21.8). The mean modified Harris hip score improved from
      46 points pre-operatively to 90 at final follow up (p < 0.001). A total of 15
      patients (17 THRs; 57%) underwent revision of the acetabular component at a mean
      of 14.6 years (7 to 20.8), all for osteolysis. Two patients (two THRs) had
      symptomatic loosening. No patient underwent femoral revision. Survival with
      revision of either component for any indication was 81% at 15 years (95% CI 60.1
      to 92.3), with 21 patients at risk. This technique may reduce the need for
      femoral osteotomy in severe DDH, while providing a good long-term functional
      result.

PMID- 25371456
TI  - Total hip replacement in patients with Down syndrome and degenerative
      osteoarthritis of the hip.
AB  - Dysplasia of the hip, hypotonia, osteopenia, ligamentous laxity, and mental
      retardation increase the complexity of performing and managing patients with Down
      syndrome who require total hip replacement (THR). We identified 14 patients (six
      males, eight females, 21 hips) with Down syndrome and degenerative disease of the
      hip who underwent THR, with a minimum follow-up of two years from 1969 to 2009.
      In seven patients, bilateral THRs were performed while the rest had unilateral
      THRs. The mean clinical follow-up was 5.8 years (standard deviation (sd) 4.7; 2
      to 17). The mean Harris hip score was 37.9 points (sd 7.8) pre-operatively and
      increased to 89.2 (sd 12.3) at final follow-up (p = 1x10(-9)). No patient
      suffered a post-operative dislocation. In three patients, four hips had revision
      THR for aseptic loosening at a mean follow-up of 7.7 years (sd 6.3; 3 to 17).
      This rate of revision THR was higher than expected. Our patients with Down
      syndrome benefitted clinically from THR at mid-term follow-up.

PMID- 25371457
TI  - Comparison between 28 mm and 32 mm ceramic-on-ceramic bearings in total hip
      replacement.
AB  - Large femoral heads have become popular in total hip replacement (THR) as a
      method of reducing the risk of dislocation. However, if large heads are used in
      ceramic-on-ceramic THR, the liner must be thinner, which may increase the risk of
      fracture. To compare the rates of ceramic fracture and dislocation between 28 mm
      and 32 mm ceramic heads, 120 hips in 109 patients (51 men and 58 women, mean age
      49.2 years) were randomised to THR with either a 28 mm or a 32 mm ceramic
      articulation. A total of 57/60 hips assigned to the 28 mm group and 55/60 hips
      assigned to the 32 mm group were followed for at least five years. No ceramic
      component fractures occured in any patient in either group. There was one
      dislocation in the 32 mm group and none in the 28 mm group (p = 0.464). No hip
      had detectable wear, focal osteolysis or prosthetic loosening. In our small study
      the 32 mm ceramic articulation appeared to be safe in terms of ceramic liner
      fracture.

PMID- 25371458
TI  - Early morbidity after aseptic revision hip arthroplasty in Denmark: a two-year
      nationwide study.
AB  - Data on early morbidity and complications after revision total hip replacement
      (THR) are limited. The aim of this nationwide study was to describe and quantify
      early morbidity after aseptic revision THR and relate the morbidity to the extent
      of the revision surgical procedure. We analysed all aseptic revision THRs from
      1st October 2009 to 30th September 2011 using the Danish National Patient
      Registry, with additional information from the Danish Hip Arthroplasty Registry.
      There were 1553 procedures (1490 patients) performed in 40 centres and we divided
      them into total revisions, acetabular component revisions, femoral stem revisions
      and partial revisions. The mean age of the patients was 70.4 years (25 to 98) and
      the median hospital stay was five days (interquartile range 3 to 7). Within 90
      days of surgery, the readmission rate was 18.3%, mortality rate 1.4%, re
      operation rate 6.1%, dislocation rate 7.0% and infection rate 3.0%. There were no
      differences in these outcomes between high- and low-volume centres. Of all
      readmissions, 255 (63.9%) were due to 'surgical' complications versus 144 (36.1%)
      'medical' complications. Importantly, we found no differences in early morbidity
      across the surgical subgroups, despite major differences in the extent and
      complexity of operations. However, dislocations and the resulting morbidity
      represent the major challenge for improvement in aseptic revision THR.

PMID- 25371459
TI  - Field testing the Unified Classification System for peri-prosthetic fractures of
      the pelvis and femur around a total hip replacement : an international
      collaboration.
AB  - The Unified Classification System (UCS) emphasises the key principles in the
      assessment and management of peri-prosthetic fractures complicating partial or
      total joint replacement. We tested the inter- and intra-observer agreement for
      the UCS as applied to the pelvis and femur using 20 examples of peri-prosthetic
      fracture in 17 patients. Each subtype of the UCS was represented by at least one
      case. Specialist orthopaedic surgeons (experts) and orthopaedic residents (pre
      experts) assessed reliability on two separate occasions. For the pelvis, the UCS
      showed inter-observer agreement of 0.837 (95% confidence intervals (CI) 0.798 to
      0.876) for the experts and 0.728 (95% CI 0.689 to 0.767) for the pre-experts. The
      intra-observer agreement for the experts was 0.861 (95% CI 0.760 to 0.963) and
      0.803 (95% 0.688 to 0.918) for the pre-experts. For the femur, the UCS showed an
      inter-observer kappa value of 0.805 (95% CI 0.765 to 0.845) for the experts and a
      value of 0.732 (95% CI 0.690 to 0.773) for the pre-experts. The intra-observer
      agreement was 0.920 (95% CI 0.867 to 0.973) for the experts, and 0.772 (95% CI
      0.652 to 0.892) for the pre-experts. This corresponds to a substantial and
      'almost perfect' inter- and intra-observer agreement for the UCS for peri
      prosthetic fractures of the pelvis and femur. We hope that unifying the
      terminology of these injuries will assist in their assessment, treatment and
      outcome.

PMID- 25371460
TI  - Clinical outcome following conversion of Girdlestone's resection arthroplasty to
      total hip replacement: a retrospective matched case-control study.
AB  - A total of 31 patients, (20 women, 11 men; mean age 62.5 years old; 23 to 81),
      who underwent conversion of a Girdlestone resection-arthroplasty (RA) to a total
      hip replacement (THR) were compared with 93 patients, (60 women, 33 men; mean age
      63.4 years old; 20 to 89), who had revision THR surgery for aseptic loosening in
      a retrospective matched case-control study. Age, gender and the extent of the pre
      operative bone defect were similar in all patients. Mean follow-up was 9.3 years
      (5 to 18). Pre-operative function and range of movement were better in the
      control group (p = 0.01 and 0.003, respectively) and pre-operative leg length
      discrepancy (LLD) was greater in the RA group (p < 0.001). The post-operative
      clinical outcome was similar in both groups except for mean post-operative LLD,
      which was greater in the study group (p = 0.003). There was a significant
      interaction effect for LLD in the study group (p < 0.001). A two-way analysis of
      variance showed that clinical outcome depended on patient age (patients older
      than 70 years old had worse pre-operative pain, p = 0.017) or bone defect
      (patients with a large acetabular bone defect had higher LLD, p = 0.006, worse
      post-operative function p = 0.009 and range of movement, p = 0.005), irrespective
      of the group. Despite major acetabular and femoral bone defects requiring complex
      surgical reconstruction techniques, THR after RA shows a clinical outcome similar
      to those obtained in aseptic revision surgery for hips with similar sized bone
      defects.

PMID- 25371461
TI  - The anteroposterior axis of the tibia in Korean patients undergoing total knee
      replacement.
AB  - The aim of this study was to find anatomical landmarks for rotational alignment
      of the tibial component in total knee replacement (TKR) in a CT-based study. Pre
      operative CT scanning was performed on 94 South Korean patients (nine men, 85
      women, 188 knees) with osteoarthritis of the knee joint prior to TKR. The tibial
      anteroposterior (AP) axis was defined as a line perpendicular to the femoral
      surgical transepicondylar axis and passing through the centre of the posterior
      cruciate ligament (PCL). The angles between the defined tibial AP axis and
      anatomical landmarks at various levels of the tibia were measured. The mean
      values of the angles between the defined tibial AP axis and the line connecting
      the anterior border of the proximal third of the tibia to the centre of the PCL
      was -0.2 degrees  (-17 to 14.1, sd 4.1). This was very close to the defined
      tibial axis, and remained so regardless of lower limb alignment and the degree of
      tibial bowing. Therefore, AP axis defined as described, is a reliable anatomical
      landmark for rotational alignment of tibial components.

PMID- 25371462
TI  - The outcome at ten years of lateral closing-wedge high tibial osteotomy:
      determinants of survival and functional outcome.
AB  - The aim of this study was to examine the functional outcome at ten years
      following lateral closing wedge high tibial osteotomy for medial compartment
      osteoarthritis of the knee and to define pre-operative predictors of survival and
      determinants of functional outcome. 164 consecutive patients underwent high
      tibial osteotomy between 2000 and 2002. A total of 100 patients (100 knees) met
      the inclusion criteria and 95 were available for review at ten years. Data were
      collected prospectively and included patient demographics, surgical details, long
      leg alignment radiographs, Western Ontario and McMaster Universities
      osteoarthritis index (WOMAC) and Knee Society scores (KSS) pre-operatively and at
      five and ten years follow-up. At ten years, 21 patients had been revised at a
      mean of five years. Overall Kaplan-Meier survival was 87% (95% confidence
      interval (CI) 81 to 94) and 79% (95% CI 71 to 87) at five and ten years,
      respectively. When compared with unrevised patients, those who had been revised
      had significantly lower mean pre-operative WOMAC Scores (47 (21 to 85) vs 65 (32
      to 99), p < 0.001), higher mean age (54 yrs (42 to 61) vs 49 yrs (26 to 66), p =
      0.006) and a higher mean BMI (30.2; 25 to 39 vs 27.9; 21 to 36, p = 0.005). Each
      were found to be risk factors for revision, with hazard ratios of 10.7 (95% CI 4
      to 28.6; pre-operative WOMAC < 45), 6.5 (95% CI 2.4 to 17.7; age > 55) and 3.0
      (95%CI 1.2 to 7.6; BMI > 30). Survival of patients with pre-operative WOMAC > 45,
      age < 55 and BMI < 30 was 97% at five and ten years. WOMAC and KSS in surviving
      patients improved significantly between pre-operative (mean 61; 32 to 99) and
      five (mean 88; 35 to 100, p = 0.001) and ten years (mean 84; 38 to 100, p =
      0.001). Older patients had better functional outcomes overall, despite their
      higher revision rate. This study has shown that improved survival is associated
      with age < 55 years, pre-operative WOMAC scores > 45 and, a BMI < 30. In patients
      over 55 years of age with adequate pre-operative functional scores, survival can
      be good and functional outcomes can be significantly better than their younger
      counterparts. We recommend the routine use of pre-operative functional outcome
      scores to guide decision-making when considering suitability for high tibial
      osteotomy.

PMID- 25371463
TI  - Low grading of the severity of knee osteoarthritis pre-operatively is associated
      with a lower functional level after total knee replacement: a prospective cohort
      study with 12 months' follow-up.
AB  - The optimal timing of total knee replacement (TKR) in patients with
      osteoarthritis, in relation to the severity of disease, remains controversial.
      This prospective study was performed to investigate the effect of the severity of
      osteoarthritis and other commonly available pre- and post-operative clinical
      parameters on the clinical outcome in a consecutive series of cemented TKRs. A
      total of 176 patients who underwent unilateral TKR were included in the study.
      Their mean age was 68 years (39 to 91), 63 (36%) were male and 131 knees (74%)
      were classified as grade 4 on the Kellgren-Lawrence osteoarthritis scale. A total
      of 154 patients (87.5%) returned for clinical review 12 months post-operatively,
      at which time the outcome was assessed using the Knee Society score. A low
      radiological severity of osteoarthritis was not associated with pain 12 months
      post-operatively. However, it was significantly associated with an inferior level
      of function (p = 0.007), implying the need for increased focus on all possible
      reasons for pain in the knee and the forms of conservative treatment which are
      available for patients with lower radiological severity of osteoarthritis.

PMID- 25371465
TI  - Clinical negligence in foot and ankle surgery: A 17-year review of claims to the
      NHS Litigation Authority.
AB  - We present a review of litigation claims relating to foot and ankle surgery in
      the NHS in England during the 17-year period between 1995 and 2012. A freedom of
      information request was made to obtain data from the NHS litigation authority
      (NHSLA) relating to orthopaedic claims, and the foot and ankle claims were
      reviewed. During this period of time, a total of 10 273 orthopaedic claims were
      made, of which 1294 (12.6%) were related to the foot and ankle. 1036 were closed,
      which comprised of 1104 specific complaints. Analysis was performed using the
      complaints as the denominator. The cost of settling these claims was more than
      L36 million. There were 372 complaints (33.7%) involving the ankle, of which 273
      (73.4%) were related to trauma. Conditions affecting the first ray accounted for
      236 (21.4%), of which 232 (98.3%) concerned elective practice. Overall, claims
      due to diagnostic errors accounted for 210 (19.0%) complaints, 208 (18.8%) from
      alleged incompetent surgery and 149 (13.5%) from alleged mismanagement. Our
      findings show that the incorrect, delayed or missed diagnosis of conditions
      affecting the foot and ankle is a key area for improvement, especially in trauma
      practice.

PMID- 25371464
TI  - Trabecular bone density of the proximal tibia as it relates to failure of a total
      knee replacement.
AB  - The relationship between post-operative bone density and subsequent failure of
      total knee replacement (TKR) is not known. This retrospective study aimed to
      determine the relationship between bone density and failure, both overall and
      according to failure mechanism. All 54 aseptic failures occurring in 50 patients
      from 7760 consecutive primary cemented TKRs between 1983 and 2004 were matched
      with non-failing TKRs, and 47 failures in 44 patients involved tibial failures
      with the matching characteristics of age (65.1 for failed and 69.8 for non
      failed), gender (70.2% female), diagnosis (93.6% OA), date of operation,
      bilaterality, pre-operative alignment (0.4 and 0.3 respectively), and body mass
      index (30.2 and 30.0 respectively). In each case, the density of bone beneath the
      tibial component was assessed at each follow-up interval using standardised,
      calibrated radiographs. Failing knees were compared with controls both overall
      and, as a subgroup analysis, by failure mechanism. Knees were compared with
      controls using univariable linear regression. Significant and continuous
      elevation in tibial density was found in knees that eventually failed by medial
      collapse (p < 0.001) and progressive radiolucency (p < 0.001) compared with
      controls, particularly in the medial region of the tibia. Knees failing due to
      ligamentous instability demonstrated an initial decline in density (p = 0.0152)
      followed by a non-decreasing density over time (p = 0.034 for equivalence). Non
      failing knees reported a decline in density similar to that reported previously
      using dual-energy x-ray absorptiometry (DEXA). Differences between failing and
      non-failing knees were observable as early as two months following surgery. This
      tool may be used to identify patients at risk of failure following TKR, but more
      validation work is needed.

PMID- 25371466
TI  - Lower limb joint replacement in patients with a history of venous
      thromboembolism.
AB  - Although patients with a history of venous thromboembolism (VTE) who undergo
      lower limb joint replacement are thought to be at high risk of further VTE, the
      actual rate of recurrence has not been reported. The purpose of this study was to
      identify the recurrence rate of VTE in patients who had undergone lower limb
      joint replacement, and to compare it with that of patients who had undergone a
      joint replacement without a history of VTE. From a pool of 6646 arthroplasty
      procedures (3344 TKR, 2907 THR, 243 revision THR, 152 revision TKR) in 5967
      patients (68% female, mean age 67.7; 21 to 96) carried out between 2009 and 2011,
      we retrospectively identified 118 consecutive treatment episodes in 106 patients
      (65% female, mean age 70; 51 to 88,) who had suffered a previous VTE. Despite
      mechanical prophylaxis and anticoagulation with warfarin, we had four recurrences
      by three months (3.4% of 118) and six by one year (5.1% of 118). In comparison,
      in all our other joint replacements the rate of VTE was 0.54% (35/6528). The
      relative risk of a VTE by 90 days in patients who had undergone a joint
      replacement with a history of VTE compared with those with a joint replacement
      and no history of VTE was 6.3 (95% confidence interval, 2.3 to 17.5). There were
      five complications in the previous VTE group related to bleeding or over
      anticoagulation.

PMID- 25371467
TI  - The natural history of the rheumatoid shoulder: a prospective long-term follow-up
      study.
AB  - The purpose of this study was to evaluate the natural history of rheumatoid
      disease of the shoulder over an eight-year period. Our hypothesis was that
      progression of the disease is associated with a decrease in function with time. A
      total of 22 patients (44 shoulders; 17 women, 5 men, (mean age 63)) with
      rheumatoid arthritis were followed for eight years. All shoulders were assessed
      using the Constant score, anteroposterior radiographs (Larsen score, Upward
      Migration-Index (UMI)) and ultrasound (US). At final follow-up, the Short Form
      36, disabilities of the arm, shoulder and hand (DASH) Score, erythrocyte
      sedimentation rate and use of anti-rheumatic medication were determined. The mean
      Constant score was 72 points (50 to 88) at baseline and 69 points (25 to 100) at
      final follow-up. Radiological evaluation showed progressive destruction of the
      peri-articular structures with time. This progression of joint and rotator cuff
      destruction was significantly associated with the Constant score. However, at
      baseline only the extent of rotator cuff disease and the UMI could predict the
      Constant score at final follow-up. A plain anteroposterior radiograph of the
      shoulder is sufficient to assess any progression of rheumatoid disease and to
      predict functional outcome in the long term by using the UMI as an indicator of
      rotator cuff degeneration.

PMID- 25371468
TI  - Glenohumeral arthrodesis for the treatment of recurrent shoulder instability in
      epileptic patients.
AB  - We report our experience with glenohumeral arthrodesis as a salvage procedure for
      epilepsy-related recurrent shoulder instability. A total of six patients with
      epilepsy underwent shoulder fusion for recurrent instability and were followed up
      for a mean of 39 months (12 to 79). The mean age at the time of surgery was 31
      years (22 to 38). Arthrodesis was performed after a mean of four previous
      stabilisation attempts (0 to 11) in all but one patient in whom the procedure was
      used as a primary treatment. All patients achieved bony union, with a mean time
      to fusion of 2.8 months (2 to 7). There were no cases of re-dislocation. One
      revision was undertaken for loosening of the metalwork, and then healed
      satisfactorily. An increase was noted in the mean subjective shoulder value,
      which improved from 37 (5 to 50) pre-operatively to 42 (20 to 70) post
      operatively although it decreased in two patients. The mean Oxford shoulder
      instability score improved from 13 pre-operatively (7 to 21) to 24 post
      operatively (13 to 36). In our series, glenohumeral arthrodesis eliminated
      recurrent instability and improved functional outcome. Fusion surgery should
      therefore be considered in this patient population. However, since the majority
      of patients are young and active, they should be comprehensively counselled pre
      operatively given the functional deficit that results from the procedure.

PMID- 25371469
TI  - Necrotising soft-tissue infections of the upper limb: risk factors for amputation
      and death.
AB  - Necrotising soft-tissue infections (NSTIs) of the upper limb are uncommon, but
      potentially life-threatening. We used a national database to investigate the risk
      factors for amputation of the limb and death. We extracted data from the Japanese
      Diagnosis Procedure Combination database on 116 patients (79 men and 37 women)
      who had a NSTI of the upper extremity between 2007 and 2010. The overall in
      hospital mortality was 15.5%. Univariate analysis of in-hospital mortality showed
      that the significant variables were age (p = 0.015), liver dysfunction (p =
      0.005), renal dysfunction (P < 0.001), altered consciousness (p = 0.049), and
      sepsis (p = 0.021). Logistic regression analysis showed that the factors
      associated with death in hospital were age over 70 years (Odds Ratio (OR) 6.6;
      95% confidence interval (CI) 1.5 to 28.2; p = 0.011) and renal dysfunction (OR
      15.4; 95% CI 3.8 to 62.8; p < 0.001). Univariate analysis of limb amputation
      showed that the significant variables were diabetes (p = 0.017) mellitus and
      sepsis (p = 0.001). Multivariable logistic regression analysis showed that the
      factors related to limb amputation were sepsis (OR 1.8; 95% CI 1.5 to 24.0; p =
      0.013) and diabetes mellitus (OR 1.6; 95% CI 1.1 to 21.1; p = 0.038). For NSTIs
      of the upper extremity, advanced age and renal dysfunction are both associated
      with a higher rate of in-hospital mortality. Sepsis and diabetes mellitus are
      both associated with a higher rate of amputation.

PMID- 25371470
TI  - Posterior iliac offset: description of a new radiological measurement of
      sacroiliac joint instability.
AB  - The purpose of this study was to describe the radiological characteristics of a
      previously unreported finding: posterior iliac offset at the sacroiliac joint and
      to assess its association with pelvic instability as measured by initial
      displacement and early implant loosening or failure. Radiographs from 42
      consecutive patients with a mean age of 42 years (18 to 77; 38 men, four women)
      and mean follow-up of 38 months (3 to 96) with Anteroposterior Compression II
      injuries, were retrospectively reviewed. Standardised measurements were recorded
      for the extent of any diastasis of the pubic symphysis, widening of the
      sacroiliac joint, static vertical ramus offset and a novel measurement (posterior
      offset of the ilium at the sacroiliac joint identified on axial CT scan). Pelvic
      fractures with posterior iliac offset exhibited greater levels of initial
      displacement of the anterior pelvis (anterior sacroiliac widening, pubic
      symphysis diastasis and static vertical ramus offset, p < 0.001,0.034 and 0.028,
      respectively). Pelvic fractures with posterior ilium offset also demonstrated
      higher rates of implant loosening regardless of fixation method (p = 0.05).
      Posterior offset of the ilium was found to be a reliable and reproducible
      measurement with substantial inter-observer agreement (kappa = 0.70). Posterior
      offset of the ilium on axial CT scan is associated with greater levels of initial
      pelvic displacement and early implant loosening.

PMID- 25371471
TI  - Radiofrequency ablation in the treatment of cartilaginous lesions in the long
      bones: results of a pilot study.
AB  - Atypical cartilaginous tumours are usually treated by curettage. The purpose of
      this study was to show that radiofrequency ablation was an effective alternative
      treatment. We enrolled 20 patients (two male, 18 female, mean age 56 years (36 to
      72) in a proof-of-principle study. After inclusion, biopsy and radiofrequency
      ablation were performed, followed three months later by curettage and adjuvant
      phenolisation. The primary endpoint was the proportional necrosis in the
      retrieved material. Secondary endpoints were correlation with the findings on
      gadolinium enhanced MRI, functional outcome and complications. Our results show
      that 95% to 100% necrosis was obtained in 14 of the 20 patients. MRI had a 91%
      sensitivity and 67% specificity for detecting residual tumour after curettage.
      The mean functional outcome (MSTS) score six weeks after radiofrequency ablation
      was 27.1 (23 to 30) compared with 18.1 (12 to 25) after curettage (p < 0.001). No
      complications occurred after ablation, while two patients developed a
      pathological fracture after curettage. We have shown that radiofrequency ablation
      is capable of completely eradicating cartilaginous tumour cells in selective
      cases. MRI has a 91% sensitivity for detecting any residual tumour.
      Radiofrequency ablation can be performed on an outpatient basis allowing a rapid
      return to normal activities. If it can be made more effective, it has the
      potential to provide better local control, while improving functional outcome.

PMID- 25371472
TI  - Prevention of dislocation of the hip in children with cerebral palsy: 20-year
      results of a population-based prevention programme.
AB  - In 1994 a cerebral palsy (CP) register and healthcare programme was established
      in southern Sweden with the primary aim of preventing dislocation of the hip in
      these children. The results from the first ten years were published in 2005 and
      showed a decrease in the incidence of dislocation of the hip, from 8% in a
      historical control group of 103 children born between 1990 and 1991 to 0.5% in a
      group of 258 children born between 1992 and 1997. These two cohorts have now been
      re-evaluated and an additional group of 431 children born between 1998 and 2007
      has been added. By 1 January 2014, nine children in the control group, two in the
      first study group and none in the second study group had developed a dislocated
      hip (p < 0.001). The two children in the first study group who developed a
      dislocated hip were too unwell to undergo preventive surgery. Every child with a
      dislocated hip reported severe pain, at least periodically, and four underwent
      salvage surgery. Of the 689 children in the study groups, 91 (13%) underwent
      preventive surgery. A population-based hip surveillance programme enables the
      early identification and preventive treatment, which can result in a
      significantly lower incidence of dislocation of the hip in children with CP.

PMID- 25371473
TI  - Is congenital talipes equinovarus a risk factor for pathological dysplasia of the
      hip? : a 21-year prospective, longitudinal observational study.
AB  - There is controversy whether congenital foot abnormalities are true risk factors
      for pathological dysplasia of the hip. Previous United Kingdom screening
      guidelines considered congenital talipes equinovarus (CTEV) to be a risk factor
      for hip dysplasia, but present guidelines do not. We assessed the potential
      relationship between pathological dysplasia of the hip and fixed idiopathic CTEV.
      We present a single-centre 21-year prospective longitudinal observational study.
      All fixed idiopathic CTEV cases were classified (Harrold and Walker Types 1 to 3)
      and the hips clinically and sonographically assessed. Sonographic Graf Type III,
      IV and radiological irreducible hip dislocation were considered to be
      pathological hip dysplasia. Over 21 years there were 139 children with 199 cases
      of fixed idiopathic CTEV feet. Sonographically, there were 259 normal hips, 18
      Graf Type II hips, 1 Graf Type III hip and 0 Graf Type IV hip. There were no
      cases of radiological or sonographic irreducible hip dislocation. Fixed
      idiopathic CTEV should not be considered as a significant risk factor for
      pathological hip dysplasia. This conclusion is in keeping with the current
      newborn and infant physical examination guidelines in which the only risk factors
      routinely screened are family history and breech presentation. Our findings
      suggest CTEV should not be considered a significant risk factor in pathological
      dysplasia of the hip.

PMID- 25371474
TI  - A comparison of the simplified olecranon and digital methods of assessment of
      skeletal maturity during the pubertal growth spurt.
AB  - Assessment of skeletal age is important in children's orthopaedics. We compared
      two simplified methods used in the assessment of skeletal age. Both methods have
      been described previously with one based on the appearance of the epiphysis at
      the olecranon and the other on the digital epiphyses. We also investigated the
      influence of assessor experience on applying these two methods. Our investigation
      was based on the anteroposterior left hand and lateral elbow radiographs of 44
      boys (mean: 14.4; 12.4 to 16.1 ) and 78 girls (mean: 13.0; 11.1 to14.9) obtained
      during the pubertal growth spurt. A total of nine observers examined the
      radiographs with the observers assigned to three groups based on their experience
      (experienced, intermediate and novice). These raters were required to determined
      skeletal ages twice at six-week intervals. The correlation between the two
      methods was determined per assessment and per observer groups. Interclass
      correlation coefficients (ICC) evaluated the reproducibility of the two methods.
      The overall correlation between the two methods was r = 0.83 for boys and r =
      0.84 for girls. The correlation was equal between first and second assessment,
      and between the observer groups (r >= 0.82). There was an equally strong ICC for
      the assessment effect (ICC <= 0.4%) and observer effect (ICC <= 3%) for each
      method. There was no significant (p < 0.05) difference between the levels of
      experience. The two methods are equally reliable in assessing skeletal maturity.
      The olecranon method offers detailed information during the pubertal growth
      spurt, while the digital method is as accurate but less detailed, making it more
      useful after the pubertal growth spurt once the olecranon has ossified.

PMID- 25371475
TI  - Non-tuberculous mycobacterial infection of the musculoskeletal system: pattern of
      infection and efficacy of combined surgical/antimicrobial treatment.
AB  - Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal tissue is a
      rare disease. An early and accurate diagnosis is often difficult because of the
      indolent clinical course and difficulty of isolating pathogens. Our goal was to
      determine the clinical features of musculoskeletal NTM infection and to present
      the treatment outcomes. A total of 29 patients (nine females, 20 males between 34
      and 85 years old, mean age 61.7 years; 34 to 85) with NTM infection of the
      musculoskeletal system between 1998 to 2011 were identified and their treatment
      retrospectively analysed. Microbiological studies demonstrated NTM in 29
      patients: the isolates were Mycobacterium intracellulare in six patients, M.
      fortuitum in three, M. abscessus in two and M. marinum in one. In the remaining
      patients we failed to identify the species. The involved sites were the
      hand/wrist in nine patients the knee in five patients, spine in four patients,
      foot in two patients, elbow in two patients, shoulder in one, ankle in two
      patients, leg in three patients and multiple in one patient. The mean interval
      between the appearance of symptoms and diagnosis was 20.8 months (1.5 to 180).
      All patients underwent surgical treatment and antimicrobial medication according
      to our protocol for chronic musculoskeletal infection: 20 patients had NTM
      specific medication and nine had conventional antimicrobial therapy. At the final
      follow-up 22 patients were cured, three failed to respond to treatment and four
      were lost to follow-up. Identifying these diseases due the initial non-specific
      presentation can be difficult. Treatment consists of surgical intervention and
      adequate antimicrobial therapy, which can result in satisfactory outcomes.

PMID- 25371476
TI  - Use of broth cultures peri-operatively to optimise the microbiological diagnosis
      of musculoskeletal implant infections.
AB  - We compared the use of broth culture medium for samples taken in theatre with the
      standard practice of placing tissue samples in universal containers. A total of
      67 consecutive patients had standard multiple samples of deep tissue harvested at
      surgery and distributed equally in theatre either to standard universal
      containers or to broth culture medium. These samples were cultured by direct and
      enrichment methods. The addition of broth in theatre to standard practice led to
      an increase in sensitivity from 83% to 95% and an increase in negative predictive
      value from 77% to 91%. Placing tissue samples directly into broth in the
      operating theatre is a simple, inexpensive way to increase the sensitivity of
      cultures from infected patients, and does not appear to compromise the
      specificity of these cultures.

PMID- 25371478
TI  - JAMSS: proteomics mass spectrometry simulation in Java.
AB  - Countless proteomics data processing algorithms have been proposed, yet few have
      been critically evaluated due to lack of labeled data (data with known identities
      and quantities). Although labeling techniques exist, they are limited in terms of
      confidence and accuracy. In silico simulators have recently been used to create
      complex data with known identities and quantities. We propose Java Mass
      Spectrometry Simulator (JAMSS): a fast, self-contained in silico simulator
      capable of generating simulated MS and LC-MS runs while providing meta
      information on the provenance of each generated signal. JAMSS improves upon
      previous in silico simulators in terms of its ease to install, minimal
      parameters, graphical user interface, multithreading capability, retention time
      shift model and reproducibility. AVAILABILITY AND IMPLEMENTATION: The simulator
      creates mzML 1.1.0. It is open source software licensed under the GPLv3. The
      software and source are available at https://github.com/optimusmoose/JAMSS.

PMID- 25371479
TI  - Detecting differential peaks in ChIP-seq signals with ODIN.
AB  - MOTIVATION: Detection of changes in deoxyribonucleic acid (DNA)-protein
      interactions from ChIP-seq data is a crucial step in unraveling the regulatory
      networks behind biological processes. The simplest variation of this problem is
      the differential peak calling (DPC) problem. Here, one has to find genomic
      regions with ChIP-seq signal changes between two cellular conditions in the
      interaction of a protein with DNA. The great majority of peak calling methods can
      only analyze one ChIP-seq signal at a time and are unable to perform DPC.
      Recently, a few approaches based on the combination of these peak callers with
      statistical tests for detecting differential digital expression have been
      proposed. However, these methods fail to detect detailed changes of protein-DNA
      interactions. RESULTS: We propose an One-stage DIffereNtial peak caller (ODIN);
      an Hidden Markov Model-based approach to detect and analyze differential peaks
      (DPs) in pairs of ChIP-seq data. ODIN performs genomic signal processing, peak
      calling and p-value calculation in an integrated framework. We also propose an
      evaluation methodology to compare ODIN with competing methods. The evaluation
      method is based on the association of DPs with expression changes in the same
      cellular conditions. Our empirical study based on several ChIP-seq experiments
      from transcription factors, histone modifications and simulated data shows that
      ODIN outperforms considered competing methods in most scenarios.

PMID- 25371481
TI  - Is aspartate aminotransferase-to-platelet ratio index a biomarker in the
      evaluation of advanced fibrosis in non-alcoholic fatty liver disease?

PMID- 25371482
TI  - Commentary on "Simple non-invasive biomarkers of advanced fibrosis in the
      evaluation of non-alcoholic fatty liver disease".

PMID- 25371480
TI  - First population-level effectiveness evaluation of a national programme to
      prevent HIV transmission from mother to child, South Africa.
AB  - BACKGROUND: There is a paucity of data on the national population-level
      effectiveness of preventing mother-to-child transmission (PMTCT) programmes in
      high-HIV-prevalence, resource-limited settings. We assessed national PMTCT impact
      in South Africa (SA), 2010. METHODS: A facility-based survey was conducted using
      a stratified multistage, cluster sampling design. A nationally representative
      sample of 10 178 infants aged 4-8 weeks was recruited from 565 clinics. Data
      collection included caregiver interviews, record reviews and infant dried blood
      spots to identify HIV-exposed infants (HEI) and HIV-infected infants. During
      analysis, self-reported antiretroviral (ARV) use was categorised: 1a: triple ARV
      treatment; 1b: azidothymidine >10 weeks; 2a: azidothymidine <=10 weeks; 2b:
      incomplete ARV prophylaxis; 3a: no antenatal ARV and 3b: missing ARV information.
      Findings were adjusted for non-response, survey design and weighted for live
      birth distributions. RESULTS: Nationally, 32% of live infants were HEI; early
      mother-to-child transmission (MTCT) was 3.5% (95% CI 2.9% to 4.1%). In total
      29.4% HEI were born to mothers on triple ARV treatment (category 1a) 55.6% on
      prophylaxis (1b, 2a, 2b), 9.5% received no antenatal ARV (3a) and 5.5% had
      missing ARV information (3b). Controlling for other factors groups, 1b and 2a had
      similar MTCT to 1a (Ref; adjusted OR (AOR) for 1b, 0.98, 0.52 to 1.83; and 2a,
      1.31, 0.69 to 2.48). MTCT was higher in group 2b (AOR 3.68, 1.69 to 7.97). Within
      group 3a, early MTCT was highest among breastfeeding mothers 11.50% (4.67% to
      18.33%) for exclusive breast feeding, 11.90% (7.45% to 16.35%) for mixed breast
      feeding, and 3.45% (0.53% to 6.35%) for no breast feeding). Antiretroviral
      therapy or >10 weeks prophylaxis negated this difference (MTCT 3.94%, 1.98% to
      5.90%; 2.07%, 0.55% to 3.60% and 2.11%, 1.28% to 2.95%, respectively).
      CONCLUSIONS: SA, a high-HIV-prevalence middle income country achieved <5% MTCT by
      4-8 weeks post partum. The long-term impact on PMTCT on HIV-free survival needs
      urgent assessment.

PMID- 25371483
TI  - The aspartate aminotransferase-to-platelet ratio and the evaluation of non
      alcoholic fatty liver disease.

PMID- 25371485
TI  - Calming the "perfect storm" in methicillin-resistant Staphylococcus aureus
      bacteremia: a call for a more balanced discussion.

PMID- 25371484
TI  - Spatial localization of recent ancestors for admixed individuals.
AB  - Ancestry analysis from genetic data plays a critical role in studies of human
      disease and evolution. Recent work has introduced explicit models for the
      geographic distribution of genetic variation and has shown that such explicit
      models yield superior accuracy in ancestry inference over nonmodel-based methods.
      Here we extend such work to introduce a method that models admixture between
      ancestors from multiple sources across a geographic continuum. We devise
      efficient algorithms based on hidden Markov models to localize on a map the
      recent ancestors (e.g., grandparents) of admixed individuals, joint with
      assigning ancestry at each locus in the genome. We validate our methods by using
      empirical data from individuals with mixed European ancestry from the Population
      Reference Sample study and show that our approach is able to localize their
      recent ancestors within an average of 470 km of the reported locations of their
      grandparents. Furthermore, simulations from real Population Reference Sample
      genotype data show that our method attains high accuracy in localizing recent
      ancestors of admixed individuals in Europe (an average of 550 km from their true
      location for localization of two ancestries in Europe, four generations ago). We
      explore the limits of ancestry localization under our approach and find that
      performance decreases as the number of distinct ancestries and generations since
      admixture increases. Finally, we build a map of expected localization accuracy
      across admixed individuals according to the location of origin within Europe of
      their ancestors. 

PMID- 25371486
TI  - Reply to Eschenauer et al.

PMID- 25371487
TI  - Vancomycin minimum inhibitory concentration in methicillin-susceptible
      Staphylococcus aureus and mortality: more than handwaving?

PMID- 25371488
TI  - Diagnostic yields in solid organ transplant recipients admitted with diarrhea.
AB  - BACKGROUND: Although diarrhea is a frequent complaint among solid organ
      transplant recipients, the contribution of infectious etiologies remains
      incompletely defined. We sought to define the etiologies of diarrhea and the
      yields of testing at our institution. METHODS: We performed a retrospective
      analysis over an 18-month period of hospitalized solid organ transplant
      recipients. We stratified diarrhea by community onset vs hospital onset of
      diarrhea. RESULTS: We identified 422 admissions (representing 314 unique
      patients) with community-onset diarrhea, and 112 admissions (representing 102
      unique patients) with hospital-onset diarrhea. The majority of community- and
      hospital-onset diarrheal episodes had no identified etiology (60.9% and 75.9%,
      respectively; P = .03), yet were also self-limited (91% and 91%, respectively; P
      = .894). Thereafter, the most frequently encountered infectious etiologies were
      Clostridium difficile infection (13.3% and 11.8%, respectively), norovirus
      enteritis (8.2% and 3%), cytomegalovirus disease or colitis (6.3% and 2.7%), and
      bacterial enterocolitis (0.9% and 0%) (P = .03). In aggregate, these entities
      represented 93.7% and 90.5% of the identified infectious etiologies,
      respectively. Protozoan causes were rarely seen. Coinfection, or the simultaneous
      detection of >=2 pathogens, occurred in 8 (1.9%) and 2 (1.8%) community- and
      hospital-onset diarrheal admissions, respectively (P = .99). CONCLUSIONS: In
      solid organ transplant recipients who presented at our institution with diarrhea,
      approximately one-third had infectious etiologies identified, consisting
      predominantly of C. difficile, norovirus, cytomegalovirus, and bacterial
      enterocolitis. Other infectious etiologies were rare.

PMID- 25371489
TI  - Hepatitis A and B immunity and vaccination in chronic hepatitis B and C patients
      in a large United States cohort.
AB  - BACKGROUND: Hepatitis A and B vaccines are effective in preventing superinfection
      and sequelae in patients with chronic hepatitis B or C. We describe immunity and
      vaccination against hepatitis A and B in chronic hepatitis patients from the US
      Chronic Hepatitis Cohort Study. METHODS: We identified chronic hepatitis B and C
      patients with healthcare utilization during 2006-2008 and 12 months of
      enrollment. We used electronic laboratory records to determine immunity and
      medical and billing records for vaccination history. Immunity against hepatitis A
      was defined by positive hepatitis A antibody or documented vaccination. Immunity
      against hepatitis B was defined as hepatitis B surface antibody level >=10 mIU/mL
      or core antibody positive, or by documented vaccination. RESULTS: Among 1635
      chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against
      hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%)
      had no testing or vaccination record. Among 5328 chronic hepatitis C patients,
      2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had
      negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or
      vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were
      immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test
      result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis
      B. CONCLUSIONS: Approximately 40% of chronic hepatitis B and C patients are
      susceptible to or have no documented immunity or vaccination against hepatitis A
      or hepatitis B. Clinicians should consider antibody testing and vaccination for
      this vulnerable population.

PMID- 25371490
TI  - Persistence of Neisseria gonorrhoeae DNA following treatment for pharyngeal and
      rectal gonorrhea is influenced by antibiotic susceptibility and reinfection.
AB  - BACKGROUND: To guide interpretation of gonorrhea tests of cure using nucleic acid
      amplification testing, this study examined the persistence of Neisseria
      gonorrhoeae DNA following treatment for pharyngeal and rectal gonorrhea. METHODS:
      Men who had sex with men diagnosed with pharyngeal or rectal gonorrhea underwent
      swabbing from the pharynx or rectum 7 and 14 days following treatment. Repeat
      testing for N. gonorrhoeae was undertaken using real-time polymerase chain
      reaction (PCR) assays targeting the opa gene and porA pseudogene. RESULTS: One
      hundred pharyngeal and 100 rectal gonorrhea infections in 190 men were included.
      For pharyngeal gonorrhea, positivity of N. gonorrhoeae DNA on both PCR assays was
      present at days 7 or 14 in 13% (95% confidence interval [CI], 6.4%-19.6%) and 8%
      (95% CI, 2.7%-13.3%), respectively. For rectal gonorrhea, DNA positivity was
      present in 6% (95% CI, 1.4%-10.7%) and 8% (95% CI, 2.7%-13.3%), respectively.
      Among 200 baseline pharyngeal and rectal isolates, there were 10 with ceftriaxone
      minimum inhibitory concentration (MIC) >=0.06 mg/L and azithromycin MIC >=0.5
      mg/L, of which 3 (30%) had DNA detected at day 14; among the 190 isolates with
      lower ceftriaxone and azithromycin MICs, only 13 (7%) had persistent DNA (odds
      ratio, 5.8 [95% CI, 1.3-25.4]; P = .019). One man initially infected with N.
      gonorrhoeae multiantigen sequence type 2400 had type 4244 infection at day 14,
      indicating reinfection. CONCLUSIONS: Pharyngeal and rectal gonorrhea DNA
      persisted in 8% of men 14 days after treatment. Persistence was associated with
      elevated ceftriaxone and azithromycin MICs. Persistence can also reflect
      reinfection.

PMID- 25371491
TI  - Reply to Kaasch et al.

PMID- 25371492
TI  - Editorial commentary: persistent gonococcal DNA: artifact or real? Further
      insights into the biology of a remarkable pathogen.

PMID- 25371493
TI  - Editorial commentary: microbiologic testing in post-solid organ transplant
      diarrhea.

PMID- 25371495
TI  - Disseminated dermal leishmaniasis caused by Leishmania siamensis in a systemic
      steroid therapy patient.
AB  - Leishmania siamensis infection was recently reported from Thailand. Clinical
      presentation of L. siamensis infections is generally related to human
      immunodeficiency virus infection. Herein, disseminated dermal L. siamensis
      infection in a systemic steroid therapy patient from Myanmar is described. 

PMID- 25371494
TI  - Versican in inflammation and tissue remodeling: the impact on lung disorders.
AB  - Versican is a proteoglycan that has many different roles in tissue homeostasis
      and inflammation. The biochemical structure comprises four different types of the
      core protein with attached glycosaminoglycans (GAGs) that can be sulfated to
      various extents and has the capacity to regulate differentiation of different
      cell types, migration, cell adhesion, proliferation, tissue stabilization and
      inflammation. Versican's regulatory properties are of importance during both
      homeostasis and changes that lead to disease progression. The GAGs that are
      attached to the core protein are of the chondroitin sulfate/dermatan sulfate type
      and are known to be important in inflammation through interactions with cytokines
      and growth factors. For a more complex understanding of versican, it is of
      importance to study the tissue niche, where the wound healing process in both
      healthy and diseased conditions take place. In previous studies, our group has
      identified changes in the amount of the multifaceted versican in chronic lung
      disorders such as asthma, chronic obstructive pulmonary disease, and
      bronchiolitis obliterans syndrome, which could be a result of pathologic,
      transforming growth factor beta driven, on-going remodeling processes. Reversely,
      the context of versican in its niche is of great importance since versican has
      been reported to have a beneficial role in other contexts, e.g. emphysema. Here
      we explore the vast mechanisms of versican in healthy lung and in lung disorders.

PMID- 25371496
TI  - Prevalence and intensity of soil-transmitted helminth infections among pre-school
      age children in 12 kindergartens in Jimma Town, southwest Ethiopia.
AB  - BACKGROUND: Pre-school age children (preSAC) remain difficult to reach in mass
      drug administration (MDA) programmes to control soil-transmitted helminth (STH)
      infections. Kindergartens provide a unique platform to increase the coverage of
      MDA in preSAC in Ethiopia, but surveys assessing STHs among preSAC in
      kindergartens are scarce. METHODS: We report the prevalence and intensity of STH
      infections among 622 preSAC in 12 kindergartens in Jimma, Ethiopia. RESULTS: STHs
      were found in all kindergartens, with prevalence exceeding 50% in 8
      kindergartens. The majority of the infections were of low intensity. CONCLUSIONS:
      This study highlights the importance of kindergartens as an additional
      opportunity for MDA in Ethiopia.

PMID- 25371497
TI  - Efficacy of diclazuril and toltrazuril in the prevention of coccidiosis in dairy
      calves under field conditions.
AB  - A blinded, controlled, randomised field study was undertaken on two commercial
      dairy farms in Germany to compare the efficacy of the anticoccidials, diclazuril
      and toltrazuril in the prevention of bovine coccidiosis. A total of 86 calves
      aged between five and six weeks were randomly allocated to two treatment and one
      untreated control groups. Calves were monitored for 78 days post-treatment by
      clinical observation, bodyweight gain, faecal oocyst counts (FOCs) and coccidia
      species differentiation. Strategic treatments had no significant effect on
      bodyweight gains (P>0.05). Whilst the number of diarrhoea days was similar for
      all three groups from days 1 to 41, there was a significant difference in the
      number and percentage of diarrhoea days from day 42 with the diclazuril-treated
      group showing only one diarrhoea day compared with 9 days (P=0.0195) and 18 days
      (P=0.0027) for the control and toltrazuril-treated groups, respectively. FOCs in
      control calves fluctuated throughout the period of study indicating continued
      coccidia challenge. FOCs in the diclazuril-treated calves declined to low levels
      post-treatment, increasing to occasional counts >500 oocysts per gram of faeces
      (OPG) between days 27 and 42, but thereafter remained low. Calves treated with
      toltrazuril also showed low FOCs until day 40 but then showed several peaks of
      oocyst output >500 OPG coinciding with days of diarrhoea. 

PMID- 25371498
TI  - Effects of increased stocking density and heat stress on growth, performance,
      carcase characteristics and skeletal properties in turkeys.
AB  - Effects of increased stocking density and heat stress on growth, feed conversion,
      carcase characteristics and skeletal system properties in turkeys were
      determined. One-day-old males (n=1674) were divided into two weight-matched
      groups exposed to different environmental conditions. Controls were reared at a
      stocking density of 2.8 birds/m(2) and at thermo-neutral temperature (TnT group),
      while the experimental group was exposed to heat-stress (HSID group) and reared
      at a stocking density of 3.4 birds/m(2) and ambient temperature increased by 5
      degrees C. At 28 days of age, 27 birds from each group were sacrificed, while at
      126 days of age, 54 birds from each group were slaughtered. Increased stocking
      density and ambient temperature during the first four weeks of life increased the
      body weight (BW) of turkeys and weight, length, volume, vertical internal and
      horizontal external diameters of the tibia in the HSID group compared with the
      TnT group (P<0.05). In turkeys older than four weeks, increased stocking density
      and ambient temperature significantly decreased daily feed intake, final BW and
      relative weight of drumstick muscle by 4.7 per cent, 4.0 per cent and 3.3 per
      cent, respectively (P<0.05). The weight, length, volume, vertical and horizontal
      diameters, cross-sectional area, second moment of inertia, volumetric bone
      mineral density, maximum elastic strength and ultimate strength of bones were
      significantly lower in turkeys in the HSID group (P<0.05) at 126 days compared
      with turkeys in the TnT group at the same age. These results indicate that, up to
      four weeks of age, turkeys tolerate increased stocking density and heat stress
      better than birds between 5 and 18 weeks of age.

PMID- 25371499
TI  - From lateral root density to nodule number, the strigolactone analogue GR24
      shapes the root architecture of Medicago truncatula.
AB  - In the rhizosphere, strigolactones not only act as crucial signalling molecules
      in the communication of plants with parasitic weeds and arbuscular mycorrhiza,
      but they also play a key role in regulating different aspects of the root system.
      Here we investigated how strigolactones influence the root architecture of
      Medicago truncatula. We provide evidence that addition of the synthetic
      strigolactone analogue GR24 has an inhibitory effect on the lateral root density.
      Moreover, treatment with GR24 of Sinorhizobium meliloti-inoculated M. truncatula
      plants affects the nodule number both positively and negatively, depending on the
      concentration. Plants treated with 0.1 uM GR24 had a slightly increased number of
      nodules, whereas concentrations of 2 and 5 uM strongly reduced it. This effect
      was independent of the autoregulation of nodulation mechanism that is controlled
      by SUPER NUMERIC NODULE. Furthermore, we demonstrate that GR24 controls the
      nodule number through crosstalk with SICKLE-dependent ethylene signalling.
      Additionally, because the expression of the nodulation marker EARLY NODULATION11
      was strongly reduced in GR24-treated plants, we concluded that strigolactones
      influence nodulation at a very early stage of the symbiotic interaction. 

PMID- 25371501
TI  - The CRISPR-Cas system for plant genome editing: advances and opportunities.
AB  - Genome editing is an approach in which a specific target DNA sequence of the
      genome is altered by adding, removing, or replacing DNA bases. Artificially
      engineered hybrid enzymes, zinc-finger nucleases (ZFNs), and transcription
      activator-like effector nucleases (TALENs), and the CRISPR (clustered regularly
      interspaced short palindromic repeats)-Cas (CRISPR-associated protein) system are
      being used for genome editing in various organisms including plants. The CRISPR
      Cas system has been developed most recently and seems to be more efficient and
      less time-consuming compared with ZFNs or TALENs. This system employs an RNA
      guided nuclease, Cas9, to induce double-strand breaks. The Cas9-mediated breaks
      are repaired by cellular DNA repair mechanisms and mediate gene/genome
      modifications. Here, we provide a detailed overview of the CRISPR-Cas system and
      its adoption in different organisms, especially plants, for various applications.
      Important considerations and future opportunities for deployment of the CRISPR
      Cas system in plants for numerous applications are also discussed. Recent
      investigations have revealed the implications of the CRISPR-Cas system as a
      promising tool for targeted genetic modifications in plants. This technology is
      likely to be more commonly adopted in plant functional genomics studies and crop
      improvement in the near future. 

PMID- 25371500
TI  - QTL analysis of root morphology, flowering time, and yield reveals trade-offs in
      response to drought in Brassica napus.
AB  - Drought escape and dehydration avoidance represent alternative strategies for
      drought adaptation in annual crops. The mechanisms underlying these two
      strategies are reported to have a negative correlation, suggesting a trade-off.
      We conducted a quantitative trait locus (QTL) analysis of flowering time and root
      mass, traits representing each strategy, in Brassica napus to understand if a
      trade-off exists and what the genetic basis might be. Our field experiment used a
      genotyped population of doubled haploid lines and included both irrigated and
      rainfed treatments, allowing analysis of plasticity in each trait. We found
      strong genetic correlations among all traits, suggesting a trade-off among traits
      may exist. Summing across traits and treatments we found 20 QTLs, but many of
      these co-localized to two major QTLs, providing evidence that the trade-off is
      genetically constrained. To understand the mechanistic relationship between root
      mass, flowering time, and QTLs, we analysed the data by conditioning upon
      correlated traits. Our results suggest a causal model where such QTLs affect root
      mass directly as well as through their impacts on flowering time. Additionally,
      we used draft Brassica genomes to identify orthologues of well characterized
      Arabidopsis thaliana flowering time genes as candidate genes. This research
      provides valuable clues to breeding for drought adaptation as it is the first to
      analyse the inheritance of the root system in B. napus in relation to drought. 

PMID- 25371503
TI  - Role of plant sensory perception in plant-animal interactions.
AB  - The sedentary lifestyle of plants can give the false impression that they are
      passive participants in interactions with other organisms and the broader
      environment. In fact, plants have evolved sophisticated perceptual abilities that
      allow them to monitor and respond to a wide range of changing biotic and abiotic
      conditions. In this paper, we discuss recent research exploring the diverse ways
      in which plant sensory abilities mediate interactions between plants and animals,
      especially insects. Such interactions include the detection and capture of animal
      prey by carnivorous plants, active plant responses to pollinator visitation, the
      perception of various cues associated with the immediate presence and feeding of
      herbivores, and plant responses to (olfactory) cues indicating the threat of
      future herbivory. We are only beginning to understand the full range of sensory
      cues that mediate such interactions and to elucidate the mechanisms by which
      plants perceive, interpret, and respond to them. Nevertheless, it is clear that
      plants continually gather information about their environments via a range of
      sensory modalities and actively respond in ways that profoundly influence their
      interactions with other organisms. 

PMID- 25371502
TI  - How do drought and warming influence survival and wood traits of Picea mariana
      saplings?
AB  - Warming and drought will occur with increased frequency and intensity at high
      latitudes in the future. How heat and water stress can influence tree mortality
      is incompletely understood. The aim of this study was to evaluate how carbon
      resources, stem hydraulics, and wood anatomy and density determine the ability of
      black spruce saplings to survive daytime or night-time warming (+ 6  degrees C in
      comparison with control) in combination with a drought period. Plant water
      relations, the dynamics of non-structural carbohydrates and starch, mortality
      rate, and wood anatomy and density of saplings were monitored. Warming, in
      conjunction with 25 d of water deficit, increased sapling mortality (10% and 20%
      in night-time and daytime warming, respectively) compared with the control
      conditions (0.8%). Drought substantially decreased gas exchange, and also pre
      dawn and mid-day leaf water potential to values close to -3MPa which probably
      induced xylem embolism (xylem air entry point, P12, being on average around -3MPa
      for this species). In addition, the recovery of gas exchange never reached the
      initial pre-stress levels, suggesting a possible loss of xylem hydraulic
      conductivity associated with cavitation. Consequently, mortality may be due to
      xylem hydraulic failure. Warmer temperatures limited the replenishment of starch
      reserves after their seasonal minimum. Lighter wood was formed during the drought
      period, reflecting a lower carbon allocation to cell wall formation, preventing
      the adaptation of the hydraulic system to drought. Saplings of black spruce
      experienced difficulty in adapting under climate change conditions, which might
      compromise their survival in the future.

PMID- 25371504
TI  - SASP, a Senescence-Associated Subtilisin Protease, is involved in reproductive
      development and determination of silique number in Arabidopsis.
AB  - Senescence involves increased expression of proteases, which may participate in
      nitrogen recycling or cellular signalling. 2D zymograms detected two protein
      species with increased proteolytic activity in senescing leaves of Arabidopsis
      thaliana. A proteomic analysis revealed that both protein species correspond to a
      subtilisin protease encoded by At3g14067, termed Senescence-Associated Subtilisin
      Protease (SASP). SASP mRNA levels and enzyme activity increase during leaf
      senescence in leaves senescing during both the vegetative or the reproductive
      phase of the plant life cycle, but this increase is more pronounced in
      reproductive plants. SASP is expressed in all above-ground organs, but not in
      roots. Putative AtSASP orthologues were identified in dicot and monocot crop
      species. A phylogenetic analysis shows AtSASP and its putative orthologues
      clustering in one discrete group of subtilisin proteases in which no other
      Arabidospsis subtilisin protease is present. Phenotypic analysis of two knockout
      lines for SASP showed that mutant plants develop more inflorescence branches
      during reproductive development. Both AtSASP and its putative rice orthologue
      (OsSASP) were constitutively expressed in sasp-1 to complement the mutant
      phenotype. At maturity, sasp-1 plants produced 25% more inflorescence branches
      and siliques than either the wild-type or the rescued lines. These differences
      were mostly due to an increased number of second and third order branches. The
      increased number of siliques was compensated for by a small decrease (5.0%) in
      seed size. SASP downregulates branching and silique production during monocarpic
      senescence, and its function is at least partially conserved between Arabidopsis
      and rice. 

PMID- 25371505
TI  - Genetic dissection of ozone tolerance in rice (Oryza sativa L.) by a genome-wide
      association study.
AB  - Tropospheric ozone causes various negative effects on plants and affects the
      yield and quality of agricultural crops. Here, we report a genome-wide
      association study (GWAS) in rice (Oryza sativa L.) to determine candidate loci
      associated with ozone tolerance. A diversity panel consisting of 328 accessions
      representing all subgroups of O. sativa was exposed to ozone stress at 60 nl l(
      1) for 7h every day throughout the growth season, or to control conditions.
      Averaged over all genotypes, ozone significantly affected biomass-related traits
      (plant height -1.0%, shoot dry weight -15.9%, tiller number -8.3%, grain weight 
      9.3%, total panicle weight -19.7%, single panicle weight -5.5%) and
      biochemical/physiological traits (symptom formation, SPAD value -4.4%, foliar
      lignin content +3.4%). A wide range of genotypic variance in response to ozone
      stress were observed in all phenotypes. Association mapping based on more than 30
      000 single-nucleotide polymorphism (SNP) markers yielded 16 significant markers
      throughout the genome by applying a significance threshold of P<0.0001.
      Furthermore, by determining linkage disequilibrium blocks associated with
      significant SNPs, we gained a total of 195 candidate genes for these traits. The
      following sequence analysis revealed a number of novel polymorphisms in two
      candidate genes for the formation of visible leaf symptoms, a RING and an EREBP
      gene, both of which are involved in cell death and stress defence reactions. This
      study demonstrated substantial natural variation of responses to ozone in rice
      and the possibility of using GWAS in elucidating the genetic factors underlying
      ozone tolerance. 

PMID- 25371506
TI  - Adaptation to altitude affects the senescence response to chilling in the
      perennial plant Arabis alpina.
AB  - In annual plants with determinate growth, sugar accumulation signals high carbon
      availability once growth has ceased, resulting in senescence-dependent nutrient
      recycling to the seeds. However, this senescence-inducing effect of sugars is
      abolished at cold temperature, where sugar accumulation is important for
      protection. Here, natural variation was exploited to analyse the effect of
      chilling on interactions between leaf senescence, sugars, and phytohormones in
      Arabis alpina, a perennial plant with indeterminate growth. Eight accessions of
      A. alpina originating from between 2090 and 3090 m above sea level in the French
      Alps were used to identify heritable adaptations in senescence, stress response,
      sugars, and phytohormones to altitude. Accessions from high altitudes showed an
      enhanced capacity for sucrose accumulation and a diminished loss of chlorophyll
      in response to chilling. At warm temperature, sucrose content was negatively
      correlated with chlorophyll content, and sucrose treatment induced leaf
      senescence. Chilling resulted in lower indole-3-acetic acid, but higher zeatin
      and jasmonic acid contents. Interactions between sugar and phytohormones included
      a positive correlation between sucrose and jasmonic acid contents that may be
      involved in promoting the stress-dependent decline in chlorophyll. These findings
      reveal regulatory interactions that underlie adaptation in the senescence and
      stress response to chilling. 

PMID- 25371507
TI  - Deep sequencing reveals important roles of microRNAs in response to drought and
      salinity stress in cotton.
AB  - Drought and salinity are two major environmental factors adversely affecting
      plant growth and productivity. However, the regulatory mechanism is unknown. In
      this study, the potential roles of small regulatory microRNAs (miRNAs) in cotton
      response to those stresses were investigated. Using next-generation deep
      sequencing, a total of 337 miRNAs with precursors were identified, comprising 289
      known miRNAs and 48 novel miRNAs. Of these miRNAs, 155 miRNAs were expressed
      differentially. Target prediction, Gene Ontology (GO)-based functional
      classification, and Kyoto Encyclopedia of Genes and Genomes (KEGG)-based
      functional enrichment show that these miRNAs might play roles in response to
      salinity and drought stresses through targeting a series of stress-related genes.
      Degradome sequencing analysis showed that at least 55 predicted target genes were
      further validated to be regulated by 60 miRNAs. CitationRank-based literature
      mining was employed to determinhe the importance of genes related to drought and
      salinity stress. The NAC, MYB, and MAPK families were ranked top under the
      context of drought and salinity, indicating their important roles for the plant
      to combat drought and salinity stress. According to target prediction, a series
      of cotton miRNAs are associated with these top-ranked genes, including miR164,
      miR172, miR396, miR1520, miR6158, ghr-n24, ghr-n56, and ghr-n59. Interestingly,
      163 cotton miRNAs were also identified to target 210 genes that are important in
      fibre development. These results will contribute to cotton stress-resistant
      breeding as well as understanding fibre development. 

PMID- 25371508
TI  - Time to flower: interplay between photoperiod and the circadian clock.
AB  - Plants precisely time the onset of flowering to ensure reproductive success. A
      major factor in seasonal control of flowering time is the photoperiod. The length
      of the daily light period is measured by the circadian clock in leaves, and a
      signal is conveyed to the shoot apex to initiate floral transition accordingly.
      In the last two decades, the molecular players in the photoperiodic pathway have
      been identified in Arabidopsis thaliana. Moreover, the intricate connections
      between the circadian clockwork and components of the photoperiodic pathway have
      been unravelled. In particular, the molecular basis of time-of-day-dependent
      sensitivity to floral stimuli, as predicted by Bunning and Pittendrigh, has been
      elucidated. This review covers recent insights into the molecular mechanisms
      underlying clock regulation of photoperiodic responses and the integration of the
      photoperiodic pathway into the flowering time network in Arabidopsis.
      Furthermore, examples of conservation and divergence in photoperiodic flower
      induction in other plant species are discussed. 

PMID- 25371511
TI  - Minocycline: an old drug for a new bug: multidrug-resistant Acinetobacter
      baumannii.

PMID- 25371512
TI  - Update on Acinetobacter species: mechanisms of antimicrobial resistance and
      contemporary in vitro activity of minocycline and other treatment options.
AB  - Among Acinetobacter species, A. baumannii and other closely related species are
      commonly implicated in nosocomial infections. These organisms are usually
      multidrug resistant (MDR), and therapeutic options to treat A. baumannii
      infections are very limited. Clinicians have been resorting to older
      antimicrobial agents to treat infections caused by MDR A. baumannii, and some of
      these agents have documented toxicity and/or are not optimized for the infection
      type to be treated. Recent clinical experience supported by antimicrobial
      susceptibility data suggests that minocycline has greater activity than other
      tetracyclines and glycylcyclines against various MDR pathogens that have limited
      therapeutic options available, including Acinetobacter species. An intravenous
      formulation of minocycline has recently become available for clinical use, and in
      contrast to most older tetracyclines, minocycline has high activity against
      Acinetobacter species. In this report, we summarized some of the characteristics
      of the tetracycline class, and quantified the minocycline activity against
      contemporary (2007-2011) isolates and its potential therapeutic role against a
      collection of 5477 A. baumannii and other relevant gram-negative organisms when
      compared directly with tetracycline, doxycycline, and other broad-spectrum
      antimicrobial agents. Acinetobacter baumannii strains were highly resistant to
      all agents tested, with the exception of minocycline (79.1% susceptible) and
      colistin (98.8% susceptible). Minocycline (minimum inhibitory concentration that
      inhibits 50% and 90% of the isolates [MIC(50/90)]: 1/8 ug/mL) displayed greater
      activity than doxycycline (MIC(50/90): 2/>8 ug/mL) and tetracycline hydrochloride
      (HCL) (only 30.2% susceptible) against A. baumannii isolates, and was
      significantly more active than other tetracyclines against Burkholderia cepacia,
      Escherichia coli, Serratia marcescens, and Stenotrophomonas maltophilia isolates.
      In vitro susceptibility testing using tetracycline HCL as a surrogate for the
      susceptibility other tetracyclines fails to detect minocycline-susceptible
      isolates and the potential utility of minocycline for the treatment of many MDR
      A. baumannii infections and other difficult-to-treat species, where there are
      often limited choices of antimicrobials.

PMID- 25371509
TI  - A mechanism of growth inhibition by abscisic acid in germinating seeds of
      Arabidopsis thaliana based on inhibition of plasma membrane H+-ATPase and
      decreased cytosolic pH, K+, and anions.
AB  - The stress hormone abscisic acid (ABA) induces expression of defence genes in
      many organs, modulates ion homeostasis and metabolism in guard cells, and
      inhibits germination and seedling growth. Concerning the latter effect, several
      mutants of Arabidopsis thaliana with improved capability for H(+) efflux (wat1
      1D, overexpression of AKT1 and ost2-1D) are less sensitive to inhibition by ABA
      than the wild type. This suggested that ABA could inhibit H(+) efflux (H(+)
      ATPase) and induce cytosolic acidification as a mechanism of growth inhibition.
      Measurements to test this hypothesis could not be done in germinating seeds and
      we used roots as the most convenient system. ABA inhibited the root plasma
      membrane H(+)-ATPase measured in vitro (ATP hydrolysis by isolated vesicles) and
      in vivo (H(+) efflux from seedling roots). This inhibition involved the core ABA
      signalling elements: PYR/PYL/RCAR ABA receptors, ABA-inhibited protein
      phosphatases (HAB1), and ABA-activated protein kinases (SnRK2.2 and SnRK2.3).
      Electrophysiological measurements in root epidermal cells indicated that ABA,
      acting through the PYR/PYL/RCAR receptors, induced membrane hyperpolarization
      (due to K(+) efflux through the GORK channel) and cytosolic acidification. This
      acidification was not observed in the wat1-1D mutant. The mechanism of inhibition
      of the H(+)-ATPase by ABA and its effects on cytosolic pH and membrane potential
      in roots were different from those in guard cells. ABA did not affect the in vivo
      phosphorylation level of the known activating site (penultimate threonine) of
      H(+)-ATPase in roots, and SnRK2.2 phosphorylated in vitro the C-terminal
      regulatory domain of H(+)-ATPase while the guard-cell kinase SnRK2.6/OST1 did
      not. 

PMID- 25371513
TI  - A review of intravenous minocycline for treatment of multidrug-resistant
      Acinetobacter infections.
AB  - Options for treatment of multidrug-resistant (MDR) Acinetobacter baumannii
      infections are extremely limited. Minocycline intravenous is active against many
      MDR strains of Acinetobacter, and Clinical and Laboratory Standards Institute
      breakpoints exist to guide interpretation of minocycline susceptibility results
      with Acinetobacter. In addition, minocycline intravenous holds a US Food and Drug
      Administration indication for treatment of infections caused by Acinetobacter.
      There is an accumulating amount of literature reporting successful use of
      minocycline intravenous for treatment of serious MDR Acinetobacter infections,
      particularly for nosocomial pneumonia. These results, coupled with the generally
      favorable tolerability of minocycline intravenous, support its use as a viable
      therapeutic option for treatment of MDR Acinetobacter infections. 

PMID- 25371514
TI  - Bad bugs need old drugs: a stewardship program's evaluation of minocycline for
      multidrug-resistant Acinetobacter baumannii infections.
AB  - BACKGROUND: Minocycline is an "old-drug" with Food and Drug Administration
      approval for the treatment of infection due to Acinetobacter species. The purpose
      of this study is to describe an Antimicrobial Stewardship Program's evaluation of
      minocycline for the treatment of patients with multidrug resistant A. baumannii
      (MDR-AB) infections. METHODS: This study evaluated hospitalized adult patients
      (September 2010 through March 2013) who received minocycline intravenously (IV)
      for a MDR-AB infection. Clinical and microbiological outcomes were analyzed.
      Secondary outcomes included infection-related mortality, length of hospital stay
      (LOS), infection-related LOS, intensive care unit (ICU) LOS, mechanical
      ventilation days, and 30-day readmission. RESULTS: A total of 55 patients
      received minocycline. Median age was 56 (23-85) years, 65% were male with an
      APACHE II score of 21 (4-41). Clinical success was achieved in 40/55 (73%)
      patients treated with minocycline monotherapy (n = 3) or in combination with a
      second active agent (n = 52). Overall 43 (78%) patients demonstrated documented
      or presumed microbiologic eradication. Infection-related mortality was 25%.
      Hospital LOS was 31 (5-132) and infection-related LOS was 16 (2-43) days. Forty
      seven (85%) patients were admitted to the ICU for a LOS of 18 (2-78) days. Thirty
      nine (71%) patients required mechanical ventilation for 6 (2-29) days. One
      patient had a 30-day readmission. CONCLUSIONS: The response rate to minocycline
      monotherapy or in combination for the treatment of MDR-AB infections is
      encouraging as therapeutic options are limited. Prospective studies in patients
      with MDR-AB infections will help establish the role of minocycline alone or in
      combination with other antimicrobials.

PMID- 25371515
TI  - Carbapenem-resistance in gram-negative bacilli and intravenous minocycline: an
      antimicrobial stewardship approach at the Detroit Medical Center.
AB  - In the era of carbapenem-resistance in Acinobacter baumannii and
      Enterobacteriaceae, there are limited treatment options for these pathogens. It
      is essential that clinicians fully assess all available therapeutic alternatives
      for these multidrug-resistant organisms. We herein describe the approach of the
      antimicrobial stewardship team at the Detroit Medical Center (DMC) for the
      evaluation and use of intravenous (IV) minocycline for the treatment of these
      resistant organisms, given potential advantages of IV minocycline over
      tigecycline and doxycycline. In vitro analyses at the DMC demonstrated good
      activity against A. baumannii (78% susceptibility), including 74% of carbapenem
      resistant strains, but limited activity against our carbapenem-resistant
      K.pneumoniae (12% susceptibility.) Based in part on these results, IV minocycline
      was added to the formulary, primarily for the treatment of carbapenem-resistant
      A. baumannii. Early experience has been positive: 6/9 (67%) of patients who
      received IV minocycline had infections due to these organisms cured, including
      6/7 (86%) who received doses of 200 mg twice daily. 

PMID- 25371516
TI  - RIG-I from waterfowl and mammals differ in their abilities to induce antiviral
      responses against influenza A viruses.
AB  - The retinoic acid-induced gene I (RIG-I) plays a crucial role in sensing viral
      RNA and IFN-beta production. RIG-I varies in length and sequence between
      different species. We assessed the functional differences between RIG-I proteins
      derived from mammals and birds. The transfection of duck caspase recruitment
      domains (CARDs) and duck RIG-I (dCARDs and dRIG-I) and goose CARDs and goose RIG
      I (gCARDs and gRIG-I) into chicken DF-1 cells increased the production of IFN
      beta mRNA and IFN-stimulated genes and decreased influenza A virus (IAV)
      replication; whereas human CARDs and RIG-I (hCARDs and hRIG-I) and mouse CARDs
      and RIG-I (mCARDs and mRIG-I) had no effect. In human 293T and A549 cells, hCARDs
      had the strongest IFN-inducing activity, followed by mCARDs, dCARDs and gCARDs.
      The IFN-inducing activity of hRIG-I was stronger than that of mRIG-I, dRIG-I and
      gRIG-I, in that order. The results showed that, although the ability of dCARDs to
      activate IFN was stronger than that of gCARDs in DF-1, 293T and A549 cells, dRIG
      I had a weaker ability to activate IFN than gRIG-I in DF-1 cells with or without
      IAV infection. These data suggest that RIG-I proteins from different species have
      different amino acid sequences and functions. This genetic and functional
      diversity renders RIG-I flexible, adaptable and capable of recognizing many
      viruses in different species. 

PMID- 25371517
TI  - Genome analysis of Cronobacter phage vB_CsaP_Ss1 reveals an endolysin with
      potential for biocontrol of Gram-negative bacterial pathogens.
AB  - Bacteriophages and their derivatives are continuously gaining impetus as viable
      alternative therapeutic agents to control harmful multidrug-resistant bacterial
      pathogens, particularly in the food industry. The reduced efficacy of
      conventional antibiotics has resulted in a quest to find novel alternatives in
      the war against infectious disease. This study describes the full-genome sequence
      of Cronobacter phage vB_CsaP_Ss1, with subsequent cloning and expression of its
      endolysin, capable of hydrolysing Gram-negative peptidoglycan. Cronobacter phage
      vB_CsaP_Ss1 is composed of 42 205 bp of dsDNA with a G+C content of 46.1 mol%. A
      total of 57 ORFs were identified of which 18 could be assigned a putative
      function based on similarity to characterized proteins. The genome of Cronobacter
      phage vB_CsaP_Ss1 showed little similarity to any other bacteriophage genomes
      available in the database and thus was considered unique. In addition, functional
      analysis of the predicted endolysin (LysSs1) was also investigated. Zymographic
      experiments demonstrated the hydrolytic activity of LysSs1 against Gram-negative
      peptidoglycan, and this endolysin thus represents a novel candidate with
      potential for use against Gram-negative pathogens. 

PMID- 25371518
TI  - Shared molecular pathways and gene networks for cardiovascular disease and type 2
      diabetes mellitus in women across diverse ethnicities.
AB  - BACKGROUND: Although cardiovascular disease (CVD) and type 2 diabetes mellitus
      (T2D) share many common risk factors, potential molecular mechanisms that may
      also be shared for these 2 disorders remain unknown. METHODS AND RESULTS: Using
      an integrative pathway and network analysis, we performed genome-wide association
      studies in 8155 blacks, 3494 Hispanic American, and 3697 Caucasian American women
      who participated in the national Women's Health Initiative single-nucleotide
      polymorphism (SNP) Health Association Resource and the Genomics and Randomized
      Trials Network. Eight top pathways and gene networks related to cardiomyopathy,
      calcium signaling, axon guidance, cell adhesion, and extracellular matrix seemed
      to be commonly shared between CVD and T2D across all 3 ethnic groups. We also
      identified ethnicity-specific pathways, such as cell cycle (specific for Hispanic
      American and Caucasian American) and tight junction (CVD and combined CVD and T2D
      in Hispanic American). In network analysis of gene-gene or protein-protein
      interactions, we identified key drivers that included COL1A1, COL3A1, and ELN in
      the shared pathways for both CVD and T2D. These key driver genes were cross
      validated in multiple mouse models of diabetes mellitus and atherosclerosis.
      CONCLUSIONS: Our integrative analysis of American women of 3 ethnicities
      identified multiple shared biological pathways and key regulatory genes for the
      development of CVD and T2D. These prospective findings also support the notion
      that ethnicity-specific susceptibility genes and process are involved in the
      pathogenesis of CVD and T2D.

PMID- 25371519
TI  - Essentiality and toxicity of vanadium supplements in health and pathology.
AB  - The biological properties of vanadium complexes have become an object of interest
      due to their therapeutic potential in several diseases. However, the mechanisms
      of action of vanadium salts are still poorly understood. Vanadium complexes are
      cofactors for several enzymes and also exhibit insulin-mimetic properties. Thus,
      they are involved in the regulation of glucose metabolism, including in patients
      with diabetes. In addition, vanadium salts may also normalize blood pressure and
      play a key role in the metabolism of the thyroid and of iron as well as in the
      regulation of total cholesterol, cholesterol HDL and triglyceride (TG) levels in
      blood. Moreover, in cases of hypoxia, vanadium compounds may improve
      cardiomyocytes function. They may also exhibit both carcinogenic and anti-cancer
      properties. These include dose- and exposure-time-dependent induction and
      inhibition of the proliferation and survival of cancer cells. On the other hand,
      the balance between vanadium's therapeutic properties and its side effects has
      not yet been determined. Therefore, any studies on the potential use of vanadium
      compounds as supplements to support the treatment of a number of diseases must be
      strictly monitored for adverse effects. 

PMID- 25371520
TI  - Lipid peroxidation, reactive oxygen species and antioxidative factors in the
      pathogenesis of gastric mucosal lesions and mechanism of protection against
      oxidative stress - induced gastric injury.
AB  - The gastric mucosa plays an important role in the physiological function of the
      stomach. This mucosa acts as gastric barrier, which protects deeper located cells
      against the detrimental action of the gastric secretory components, such as acid
      and pepsin. Integrity of the gastric mucosa depends upon a variety of factors,
      such as maintenance of microcirculation, mucus-alkaline secretion and activity of
      the antioxidizing factors. The pathogenesis of gastric mucosal damage includes
      reactive oxygen species (ROS), because of their high chemical reactivity, due to
      the presence of uncoupled electron within their molecules. Therefore they cause
      tissue damage, mainly due to enhanced lipid peroxidation. Lipid peroxides are
      metabolized to malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). The local
      increase of MDA and 4-HNE concentration indicates ROS-dependent tissue damage.
      Superoxide dismutase (SOD) is the main enzyme, which neutralizes ROS into less
      noxious hydrogen peroxide. A decrease of SOD activity is an indicator of
      impairment of the protective mechanisms and significantly contributes to cell
      damage. Hydrogen peroxide is further metabolized to water in the presence of
      reduced glutathione (GSH). GSH can also work synergetically with SOD to
      neutralize ROS. The reactions between GSH and ROS yields glutathione free radical
      (GS(*)), which further reacts with GSH leading to free radical of glutathione
      disulphide (GSSG(*)). This free radical of GSSG can then donate an electron to
      the oxygen molecule, producing O2 (*-) Subsequently, O2 (*-) is eliminated by
      SOD. Adecrease of the GSH level has detrimental consequences for antioxidative
      defense cellular properties. Gastric mucosa, exposed to stress conditions,
      exhibits an enhancement of lipid peroxidation (increase of MDA and 4-HNE), as
      well as a decrease of SOD activity and GSH concentration. This chain reaction of
      ROS formation triggered by stress, appears to be an essential mechanism for
      understanding the pathogenesis of stress - induced functional disturbances in the
      gastric mucosa leading to ulcerogenesis. 

PMID- 25371521
TI  - Skeletal muscle wasting occurs in adult rats under chronic treatment with
      paracetamol when glutathione-dependent detoxification is highly activated.
AB  - The use of glutathione (GSH) and sulfate for the detoxification of paracetamol
      (acetaminophen, APAP) could occur at the expense of the physiological uses of
      cysteine (Cys). Indeed GSH and sulfate both originate from Cys. Significant APAP
      induced Cys loss could generate alterations in GSH and protein metabolisms
      leading to muscle wasting. The study aimed to investigate the effects of chronic
      treatment with APAP on whole-body and tissue homeostasis (mass, GSH, proteins,
      and nitrogen balance) in relation to sulfur losses through APAP-detoxification
      pathways. Adult male Wistar rats were fed 0% APAP, 0.5% APAP or 1% APAP diets for
      17 days. APAP doses were respectively around and largely above the threshold of
      sulfation saturation for rats. During the last days, the rats were placed in
      metabolic cages in order to quantify N balance and urinary APAP metabolites.
      Gastrocnemius muscle mass, protein and GSH contents, N balance and plasma free
      cyst(e)ine were 8% (P=0.02), 7% (P=0.03), 26% (P=0.01), 37% (P=0.01), and 33%
      (P=0.003) lower in the 1% APAP group than in the 0% APAP group, respectively.
      There was no significant difference in these parameters between the 0.5% APAP
      group and the 0% APAP group. Muscle wasting occurred when the detoxification of
      APAP through the GSH-dependent pathway was highly activated. Muscle protein
      synthesis could have been reduced due to a shortage in Cys and/or an increase in
      protein degradation in response to intra-muscular oxidative stress. Hence,
      without dietary sulphur amino acid increase, peripheral bioavailability of Cys
      and muscle GSH are potential players in the control of muscle mass under chronic
      treatment with APAP, an analgesic medication of widespread use, especially in the
      elderly. 

PMID- 25371522
TI  - Role of Mas receptor antagonist (A779) on pressure diuresis and natriuresis and
      renal blood flow in the absence of angiotensin II receptors type 1 and 2 in
      female and male rats.
AB  - Sexual differences in blood pressure are associated with angiotensin 1-7 (Ang1-7)
      and its receptor and enzyme function targeting. Blockade of angiotensin II
      (AngII) receptors type 1 and 2 (AT1R and AT2R) inhibits some actions of Ang1-7.
      We described the role of Ang1-7 receptor (MasR) antagonist (A779) on kidney
      hemodynamics when AT1R and AT2R are blocked with losartan and PD123319. In
      anaesthetized male and female rats after blockade of both AT1R and AT2R, the
      renal perfusion pressure (RPP) was controlled in two levels of 80 and 100 mmHg
      via an adjustable clamp placed around the aorta above the level of the renal
      arteries. Then, the effects of saline vehicle and MasR blocker (A779) were tested
      on pressure natriuresis and diuresis, renal blood flow (RBF), and renal vascular
      resistance (RVR). In the absence of AT1R and AT2R; RVR, RBF/wet kidney tissue
      weight, and serum level of renin did not alter in both genders either MasR was
      blocked or not. However, urine flow rate (UF) and sodium excretion (UNaV)
      increased significantly at the pressure level of 100 mmHg in the presence of MasR
      in male (P<0.05) but not in female rats. When AT1R and AT2R were blocked, the
      impact of MasR is gender-related in pressure natriuresis and diuresis, and
      pressure natriuresis and diuresis in male rats (not female) increases in the
      presence of MasR. 

PMID- 25371523
TI  - Countercurrent transfer of dopamine from venous blood in the cavernous sinus to
      the arterial blood supplying the brain - the perfused rabbit head as an
      experimental model.
AB  - The objective of the current study was to check whether countercurrent transfer
      of dopamine occurs in the cavernous sinus of the rabbit and whether the rabbit
      can be used as an animal model to study cavernous sinus function. After
      exsanguination of the animal, oxygenated and warmed (37 degrees C) Hanseneleit
      Krebs buffer with autologous or homologous blood (in a 3:1 or 1:1 ratio) was
      pumped through both common carotid arteries into the head (60 ml/min; 80-100 mm
      Hg) and radiolabeled dopamine (3(H)-DA, 10 MUCi) was infused into the cavernous
      sinus through the angular oculi vein. Cerebral blood from the basilar artery was
      collected from the cannulated vertebral artery during 3(H)-DA infusion and for 10
      minutes after completion of infusion. Selected brain tissue samples were
      collected after completion of the head perfusion. It was demonstrated that
      dopamine can penetrate from the rabbit's cavernous sinus to the internal carotid
      artery supplying the brain. Dopamine permeation was greater when the rabbit head
      was perfused with buffer and blood in a 3:1 ratio than with 1:1 (P<0.01). When
      the head was perfused with buffer and blood in a 3:1 ratio, significant
      radioactivity was found in samples collected from the brain basilar artery during
      and after 3(H)-DA infusion (P<0.001). The radioactivity was identified as 34.13
      +/- 2.7% unmetabolized 3(H)-DA and 65.9 +/- 2.7% its metabolites. Significant
      radioactivity was also found in some brain tissue samples in both groups
      (P<0.05). The concentration of free radiolabeled dopamine particles in the
      dialysate of blood plasma and plasma diluted with buffer did not differ
      significantly. Because the structures of the cavernous sinus and cavernous
      fragment of the internal carotid artery of the rabbit are similar to those in
      humans, it suggests that rabbits can serve as a model for experimental
      physiological studies of cavernous sinus function and retrograde dopamine
      transfer in the cavernous sinus should be considered as an important link in the
      genesis of Attention Deficit Hyperactivity Disorder (ADHD) and Parkinson's
      disease. 

PMID- 25371524
TI  - Dynamics of sodium retention in preascitic cirrhotic rats assessed through
      parathyroid hormone injection.
AB  - Extracellular Ca(++) stimulates membrane-bound calcium-sensing receptors (CaRs).
      CaRs stimulation leads to PGE2-mediated decrease in protein content of Na(+)-K(+)
      2Cl(-) co-transporters (BSC-1) in the thick ascending limb (TAL) of Henle's loop
      and of aquaporin 2 (AQP2) water channels in collecting ducts. Parathyroid hormone
      (PTH) increases CaRs and decreases BSC-1 and AQP2 tubular content. To assess the
      Ca(++)-dependent diuretic system in preascitic cirrhosis, we evaluated renal
      function, hormonal status, PGE2 urinary excretion, and renal content of BSC-1 and
      CaRs in three groups of rats: control rats received s.c. 5% glucose solution; two
      groups of rats with CCl4-induced preascitic cirrhosis received either s.c.
      glucose solution or five s.c. doses of 10 mcg/Kg PTH (one dose every 12 hours)
      prior to study. Cirrhotic rats, when compared to controls, showed reduced urine
      volume and sodium excretion; moreover, western blot analysis revealed reduced
      CaRs and increased BSC-1 protein content in cirrhotic rat kidneys. S.c.
      administration of PTH normalized urine and sodium excretion in cirrhotic rats and
      also increased renal plasma flow, PGE2 urinary excretion, and free-water
      clearance. Finally, PTH reduced BSC-1 and augmented CaRs content in cirrhotic rat
      kidneys. In conclusion, in preascitic cirrhosis sodium retention is associated
      with down-regulation of renal CaRs and up-regulation of tubular Na(+)-K(+)-2Cl(-)
      co-transporters. PTH returns these biomolecular changes, along with sodium and
      urine excretions, to normality, suggesting that exaggerated sodium reabsorption
      occurs primarily in the Henle's loop in preascitic cirrhosis. 

PMID- 25371525
TI  - Proopiomelanocortin but not vasopressin or renin-angiotensin system induces
      resuscitative effects of central 5-HT1A activation in haemorrhagic shock in rats.
AB  - The aim of this study was to determine the effectory mechanisms: vasopressin,
      renin-angiotensin system and proopiomelanocortin-derived peptides (POMC),
      partaking in the effects of serotonin through central serotonin 1A receptor (5
      HT1A) receptors in haemorrhagic shock in rats. The study was conducted on male
      Wistar rats. All experimental procedures were carried out under full anaesthesia.
      The principal experiment included a 2 hour observation period in haemorrhagic
      shock. Drugs used - a selective 5-HT1A agonist 8-OH-DPAT (5 MUg/5 MUl); V1a
      receptor antagonist [beta-mercapto-beta, beta-cyclo-pentamethylenepropionyl(1),O
      me-Tyr(2),Arg(8)]AVP (10 MUg/kg); angiotensin type I receptor antagonist (AT1)
      ZD7155 (0.5 mg/kg, i.v.); angiotensin-converting-enzyme inhibitor captopril (30
      mg/kg, i.v.); melanocortin type 4 (MC4) receptor antagonist HS014 (5 MUg,
      i.c.v.). There was no influence of ZD715, captopril or blocking of the V1a
      receptors on changes in the heart rate (HR), mean arterial pressure (MAP),
      peripheral blood flow or resistance caused by the central stimulation of 5-HT1A
      receptors (P>=0.05). However, selective blocking of central MC4 receptors caused
      a slight, but significant decrease in HR and MAP (P<0.05). POMC derivatives
      acting via the central MC4 receptor participate in the resuscitative effects of 8
      OH-DPAT. The angiotensin and vasopressin systems do not participate in these
      actions. 

PMID- 25371527
TI  - Bastadin 12 and ryanodine reveal similarities between thapsigargin- and
      tetrabromobisphenol A-induced intracellular Ca(2+) release in cultured cerebellar
      granule cells.
AB  - Tetrabromobisphenol A (TBBPA) is a commonly used brominated flame retardant with
      recognized neuro- and cytotoxic properties that are presumably mediated by
      intracellular Ca(2+) release. Other studies have demonstrated that ryanodine is
      able to inhibit Ca(2+) efflux from skeletal sarcoplasmic reticulum (SR) membranes
      in response to the known Ca(2+) releaser thapsigargin, provided that the
      macrocyclic brominated tyrosine derivative bastadin 5 is also present. Similar
      effects supporting the role of ryanodine receptors in thapsigargin-evoked Ca(2+)
      release have been observed in primary cultures of rat cerebellar granule cells
      (CGCs). Here, we used CGCs and the fluorescent intracellular Ca(2+) probe fluo-3
      to test the following hypotheses: (1) TBBPA shares Ca(2+) releasing properties
      with thapsigargin, and (2) synthetic bastadin 12 can replace bastadin 5 as a
      pharmacological tool to identify these similarities. The results demonstrated
      that either 200 nM thapsigargin or 30 MUM bastadin 12 alone induced an increase
      in the intracellular Ca(2+) level in CGCs, whereas 2.5 and 10 MUM bastadin 12 had
      no effect on the basal Ca(2+) concentration. The thapsigargin-induced Ca(2+)
      release was partially reduced by co-administration of either 2.5 MUM bastadin 12
      or 200 MUM ryanodine, and the release of Ca(2+) was nearly completely attenuated
      by these compounds when they were given together. TBBPA (5, 10 and 25 MUM)
      administration caused a concentration-dependent increase in CGC Ca(2+) levels.
      Administration of 2.5 MUM bastadin 12 with 200 MUM ryanodine blocked the increase
      in intracellular Ca(2+) evoked by 10 MUM TBBPA, although these compounds were
      ineffective when applied separately. These results indicate that bastadin 12 may
      replace bastadin 5 when testing the ability of ryanodine to inhibit Ca(2+)
      release from the intracellular stores of cultured neurons, and our findings
      support the hypothesis that TBBPA and thapsigargin induce intracellular Ca(2+)
      release through a common mechanism. 

PMID- 25371526
TI  - Chronic but not acute antidepresant treatment alters serum zinc/copper ratio
      under pathological/zinc-deficient conditions in mice.
AB  - Depression is the leading psychiatric disorder with a high risk of morbidity and
      mortality. Clinical studies report lower serum zinc in depressed patients,
      suggesting a strong link between zinc and mood disorders. Also copper as an
      antagonistic element to zinc seems to play a role in depression, where elevated
      concentration is observed. In the present study we investigated serum copper and
      zinc concentration after acute or chronic antidepressant (AD) treatment under
      pathological/zinc-deficient conditions. Zinc deficiency in mice was induced by a
      special diet administered for 6 weeks (zinc adequate diet - ZnA, contains 33.5
      mgZn/kg; zinc deficient diet - ZnD, contains 0.2 mgZn/kg). Animals received acute
      or chronically saline (control), imipramine, escitalopram, reboxetine or
      bupropion. To evaluate changes in serum copper and zinc concentrations the total
      reflection X-ray fluorescence (TXRF) and flame atomic absorption spectrometry
      (FAAS) was performed. In ZnD animals serum zinc level was reduced after acute ADs
      treatment (similarly to vehicle treatment), however, as demonstrated in the
      previous study after chronic ADs administration no differences between both ZnA
      and ZnD groups were observed. Acute ADs in ZnD animals caused different changes
      in serum copper concentration with no changes after chronic ADs treatment. The
      calculated serum Zn/Cu ratio is reduced in ZnD animals (compared to ZnA subjects)
      treated with saline (acutely or chronically) and in animals treated acutely with
      ADs. However, chronic treatment with ADs normalized (by escitalopram, reboxetine
      or bupropion) or increased (by imipramine) this Zn/Cu ratio. Observed in this
      study normalization of serum Zn/Cu ratio in depression-like conditions by chronic
      (but not acute) antidepressants suggest that this ratio may be consider as a
      marker of depression or treatment efficacy. 

PMID- 25371528
TI  - Effect of cannabinoid receptors 1 modulation on osteoporosis in a rat model of
      different ages.
AB  - Osteoporosis is a common health problem. The endocannabinoid pathway has been
      implicated as an important regulator of bone turnover. Rimonabant is a potent
      cannabinoid receptor1 (CB1) receptor antagonist with wide therapeutic use as an
      antiobesity drug that has been withdrawn due to side effects in the form of
      depression and suicidal attacks. This study investigated whether glucocorticoid
      induced bone loss is linked to CB1 signaling and whether modulation of CB1
      function affects the deleterious effects of glucocorticoid treatment on bone
      remodeling in rats. Sixty four rats were divided into two main groups: group 1
      (G1) consisted of 12-14 month old rats and group 2 (G2) consisted of 3-4 month
      old rats. Each main group subdivided into four subgroups as follows: (NC1) and
      (NC2), the negative control groups, (MP1) and (MP2), received methylprednisolone
      (glucocorticoid), (RIM1) and (RIM2), received rimonabant, (MP + RIM1) and (MP +
      RIM2) received methylprednisolone with rimonabant. There was a significant
      decrease in bone mineral density (BMD) and bone mineral content (BMC) of the
      tibia bones together with a decrease in osteoprotegrin (OPG) expression but with
      a significant increase in receptor activator of nuclear factor kappa B ligand
      (RANKL) expression in osteoporotic rats. These parameters were reversed with co
      administration of rimonabant with methylprednisolone in young rats, though it
      increased the severity of osteoporosis in older rats. Image analysis technique
      revealed that there was a significant improvement in cortical bone thickness
      (CBT) and mean trabecular bone density (TBD) in young group only after rimonabant
      either alone or with glucocorticoid. CB1 receptors play age related different
      roles in bone turnover. So, CB1 antagonist can be used to prevent corticosteroid
      induced osteoporosis in young age but should be avoided in old age. 

PMID- 25371529
TI  - The role of local and systemic cytokines in patients infected with Clostridium
      difficile.
AB  - It is widely accepted that the pathogenesis of Clostridium difficile infection
      (CDI) is multifactorial, dependent on pathogen virulence factors produced by the
      organism as well as disorders of the gastrointestinal tract, the alteration in
      intestinal flora and the immune response of the host. In particular, the immune
      response in the course of CDI and the involvement of cytokines in the
      pathogenesis of CDI is not fully understood. The aim of our study was to evaluate
      the relationship between proinflammatory and anti-inflammatory cytokines and the
      course of CDI in vivo. We prospectively studied 80 patients. Our study group
      included 40 patients aged 30-87 years (mean age 66.9 years) with CDI hospitalized
      at Infectious Diseases Department and Gastroenterology and Hepatology Clinic,
      University Hospital in Cracow, and 40 healthy volunteers aged 24-62 years (mean
      age 51.1 years). The serum concentrations of cytokines IL-1beta, IL-6, IL-8, IL
      10, tumor necrosis factor (TNF-alpha), myeloperoxidase (MPO), and prostaglandin
      E2 (PGE2) were measured using ELISA assays. Additionally, the routine biochemical
      parameters were assessed including the following: white blood cells with
      differential leukocyte count, platelets counts, and blood plasma levels of
      creatinine, alanine transaminase, and C-reactive protein were determined. We
      noted a significant increase in the concentration of the following cytokines in
      the CDI group when compared to the control group: IL-1b (4.7 vs. 3.6 pg/ml), IL-6
      (21.0 vs. 0.04 pg/ml), IL-10 (8.5 vs. 0.5 pg/ml), TNF-alpha (7.1 vs. 0.09 pg/ml).
      In addition the serum concentration of MPO (1056.0 vs. 498.0 pg/ml), and PGE2
      (2036.7 vs. 1492.0 pg/ml) showed a significant increase in CDI patients as
      compared with control subjects. Most CDI patients did not show any increase in
      the concentration of IL-8. We did observe a direct relationship between TNF-alpha
      and creatinine. The course of CDI is characterized by an initial local
      inflammatory process followed by a systemic inflammatory response, which
      manifests clinically as fever, and includes leukocytosis, an increase in the
      level of neutrophils in the blood, and an increase in the serum concentrations of
      TNF-alpha, IL-1beta, IL-6, IL-10, MPO and PGE2. Despite the leading role of IL-8
      in the local inflammatory process, we postulate TNF-alpha and IL-6 play a key
      role in the systemic inflammatory response in CDI, and the plasma TNF-alpha level
      seems to act as a major factor of poor prognosis in patients with CDI. 

PMID- 25371530
TI  - Leukotrienes biosynthesis in vascular surgery patients during perioperative
      period.
AB  - Leukotrienes (LTs), highly bioactive lipid mediators play a major role in
      inflammation, wound healing and in the development of atherosclerosis. LTs
      biosynthesis have been suggested to be increased in myocardial infarction (MI)
      and in surgical patients with abdominal aortic aneurysms. Among LTs, Cysteinyl
      LTs have the most potent biological properties and their production is well
      reflected by LTE4 concentration in urine (uLTE4). Aim of the study was to
      evaluate perioperative biosynthesis of uLTE4 in noncardiac vascular surgery
      patients, and its impact on patients' outcomes. Twenty eight consecutive patients
      aged 61.5 (59.0-72.5) that undergone an elective surgery for abdominal aortic
      aneurysm (AAA; n=6) or peripheral artery disease (PAD; n=22) were studied. uLTE4
      was measured in urine samples using ELISA: before surgery (LT0), 6 hours
      postoperatively (LT1), and on three following days (LT2-LT4), and the results
      were adjusted for the urinary creatinine concentration. Patients were followed-up
      for 30-days for cardio-vascular complications including myocardial infarction
      (MI) with active post-surgery troponin T screening. One way analysis of variance
      (ANOVA) for repeated measurements and logistic regression tests were used to
      analyse the data with P<05 considered significant. Excretion of uLTE4 raised in
      the first two urine sample (LT1 and LT2) after surgery as compared to
      preoperative baseline value (LT0) (P=0.008) and returned to normal values on the
      second day (LT3). Patients that suffered MI during postoperative period had
      increased uLTE4 levels when compared to the no-MI patients (P=0.006). In
      conclusion we state that uLTE4 biosynthesis is increased shortly after surgery
      and returns to the preoperative level on the second day. The increase in uLTE4
      biosynthesis is higher in patients that suffer MI after surgery, however this
      warrants further investigations. 

PMID- 25371531
TI  - Peroxisome proliferator activated receptor ligands affect progesterone and 17beta
      estradiol secretion by porcine corpus luteum during early pregnancy.
AB  - In the present study we investigated the effect of peroxisome proliferator
      activated receptor (PPAR) ligands on progesterone (P4) and 17beta-estradiol (E2)
      secretion and 3b-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta
      HSD) mRNA abundance in porcine corpora lutea (CL) collected on days 10-12 and 14
      16 of the estrous cycle or pregnancy. The PPAR agonists reduced P4 secretion by
      the CL during pregnancy whereas they were ineffective during the estrous cycle.
      An inhibitory effect of WY-14643 (PPARalpha agonist) on P4 release was noted on
      days 14-16 of pregnancy. The treatment of the CL with L-165,045 (PPARbeta
      agonist) diminished P4 release by the tissue during both stages of pregnancy. A
      natural PPARgamma agonist, PGJ2, reduced P4 release on days 14-16 or days 10-12
      of pregnancy, respectively. Rosiglitazone (PPARgamma agonist) inhibited P4
      secretion by the CL on days 10-12 of pregnancy. In turn, PPARalpha ligands effect
      on E2 release was differential. While PPARgamma activator diminished E2 secretion
      by the CL explants during all tested stages of the estrous cycle and pregnancy,
      PPARbeta ligands did not induce any change in E2 level. In turn, PPARbeta agonist
      reduced E2 release by the tissue during both stages of pregnancy but did not
      affect the secretion during the estrous cycle. In the present study there was a
      lack of PPAR ligands effect on 3beta-HSD mRNA abundance. In summary, the results
      suggest that PPARs are involved in the regulation of progesterone and 17beta
      estradiol release by porcine CL. Porcine CL indicates a different receptivity to
      PPAR ligands depending on the reproductive status of animals. 

PMID- 25371532
TI  - Proteome of spleen CD4 lymphocytes in mouse preimplantation pregnancy.
AB  - Pregnancy exerts profound impact on female immune system. The first signs of
      pregnancy recognition by immune system are observed even before implantation. The
      most visible effects are present in the local compartment, i.e. in uterine
      draining lymph nodes and the decidua, while peripheral changes are less obvious.
      In our recent paper we indicated that costimulation phenotype of APCs in spleens
      of female mice during the preimplantation period of pregnancy differs from mice
      in pseudopregnancy. However, the effect of differential costimulation in the
      context of the T lymphocyte function at periphery in early pregnancy is still
      unknown. For that reason, we decided to investigate global protein expression in
      splenic CD4(+) lymphocytes in order to identify and validate the most important
      biomarkers characteristic for the preimplantation period of pregnancy at
      periphery. Two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) were
      utilized to analyze the protein expression pattern of magnetically sorted CD4(+)
      lymphocytes from spleens of pregnant and pseudopregnant females at 3.5 days after
      mating. The first goal of this study was to create a 2-DE map of the splenic
      CD4(+) T cells of pregnant mice. As a result, 106 protein spots from 373 were
      identified using MS. The comparison of lymphocyte protein patterns between
      pregnant and pseudopregnant mice depicted differential expression of 11
      identified proteins belonging to the group of proteins involved in cytoskeletal
      structure, cell motility and metabolism. Profoundly diminished expression of
      cofilin-1, F-actin capping protein subunit alpha and malate dehydrogenase
      proteins in lymphocytes of pregnant mice indicates that preimplantation pregnancy
      could change the activation state of peripheral CD4(+) lymphocytes. 

PMID- 25371533
TI  - The influence of moderate-intensity physical effort on peripheral blood in adults
      with Down syndrome - a pilot study.
AB  - The aim of this study was to evaluate the influence of a six-week aerobic
      training on peripheral blood in adults with Down syndrome. Fifteen men with Down
      syndrome (average age 22.4 years +/- 0.91) with moderate or severe intellectual
      disability took part in the study. Patients underwent a training program three
      times a week for six weeks. Venous blood samples of 10 ml were collected from
      every examined patient, 24 hours before and after the exercise. The blood samples
      were submitted to hematological examination (hematocrit, fibrinogen, plasma
      viscosity, red blood cell (RBC) number, RBC indicators: mean corpuscular volume
      (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular
      hemoglobin (MCH)), reduced glutathione (GSH) level and number of macrocytes,
      polikilocytrometric examination of RBC and rheological blood examination
      (elongation index (EI), aggregation index (AI), syllectogram amplitude (AMP),
      aggregation half time (t1/2)) was made by LORCA. Amoderate six-week physical
      training performed on a cycloergometer resulted in a statistically significant
      decrease in the MCV value, hematocrit and plasma viscosity. The six-week
      cycloergometer training caused a statistically significant increase in the GSH
      level and erythrocyte pliability at a shear stress of 0.58 Pa. 

PMID- 25371534
TI  - Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate
      vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled
      study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals are at
      increased risk of herpes zoster (HZ), even in the antiretroviral therapy (ART)
      era. Because concerns exist about the use of live-attenuated vaccines in
      immunocompromised individuals, a subunit vaccine may be an appropriate
      alternative. METHODS: This phase 1/2, randomized, placebo-controlled study
      evaluated the immunogenicity and safety of an investigational HZ subunit vaccine
      (HZ/su). Three cohorts of HIV-infected adults aged >=18 years were enrolled: 94
      ART recipients with a CD4(+) T-cell count of >=200 cells/mm(3), 14 ART recipients
      with a CD4(+) T-cell count of 50-199 cells/mm(3), and 15 ART-naive adults with a
      CD4(+) T-cell count of >=500 cells/mm(3). Subjects received 3 doses of HZ/su (50
      ug varicella-zoster virus glycoprotein E [gE] combined with AS01B adjuvant) or 3
      doses of saline at months 0, 2, and 6. RESULTS: One month after dose 3, serum
      anti-gE antibody concentrations and frequencies of gE-specific CD4(+) T cells
      were higher following HZ/su vaccination than after receipt of saline (P < .0001).
      Median cell-mediated immune responses peaked after dose 2. Humoral and cell
      mediated immune responses persisted until the end of the study (month 18). No
      vaccination-related serious adverse events were reported. No sustained impact on
      HIV load or CD4(+) T-cell count was noted following vaccinations. CONCLUSIONS:
      HZ/su was immunogenic and had a clinically acceptable safety profile in HIV
      infected adults. CLINICAL TRIALS REGISTRATION: NCT01165203.

PMID- 25371536
TI  - Stent coverage and neointimal proliferation in bare metal stents postdilated with
      a Paclitaxel-eluting balloon versus everolimus-eluting stents: prospective
      randomized study using optical coherence tomography at 6-month follow-up.
AB  - BACKGROUND: In this randomized trial, strut coverage and neointimal proliferation
      of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug
      eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at
      6-month follow-up using optical coherence tomography. We hypothesized sufficient
      stent coverage at follow-up. METHODS AND RESULTS: A total of 105 lesions in 90
      patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the
      SeQuent Please DEB (n=54). At follow-up, comparable results on the primary
      optical coherence tomography end point (percentage uncovered struts 5.64+/-9.65%
      in BMS+DEB versus 4.93+/-9.29% in DES; P=0.366) were found. Thus, BMS+DEB
      achieved the prespecified noninferiority margin of 5% uncovered struts versus DES
      (difference between treatment means, 0.71%; one-sided upper 95% confidence
      interval, 4.14%; noninferiority P=0.04). Optical coherence tomography analysis
      showed significantly more global neointimal proliferation in the BMS+DEB group
      (15.7+/-7.8 versus 11.0+/-5.2 mm(3) proliferation volume/cm stent length;
      P=0.002). No significant focal in-stent stenosis analyzed with angiography
      (percentage diameter stenosis at follow-up, 22.8+/-11.9 versus 16.9+/-10.4;
      P=0.014) and optical coherence tomography (peak local area stenosis, 39.5+/-13.8%
      versus 36.8+/-15.6%; P=0.409) was found. CONCLUSIONS: Good stent strut coverage
      of >94% was found in both therapy groups. Despite greater suppression of global
      neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically
      relevant focal restenosis at 6-month follow-up. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01056744.

PMID- 25371538
TI  - Targeting multiple types of tumors using NKG2D-coated iron oxide nanoparticles.
AB  - Iron oxide nanoparticles (IONPs) hold great potential for cancer therapy.
      Actively targeting IONPs to tumor cells can further increase therapeutic efficacy
      and decrease off-target side effects. To target tumor cells, a natural killer
      (NK) cell activating receptor, NKG2D, was utilized to develop pan-tumor targeting
      IONPs. NKG2D ligands are expressed on many tumor types and its ligands are not
      found on most normal tissues under steady state conditions. The data showed that
      mouse and human fragment crystallizable (Fc)-fusion NKG2D (Fc-NKG2D) coated IONPs
      (NKG2D/NPs) can target multiple NKG2D ligand positive tumor types in vitro in a
      dose dependent manner by magnetic cell sorting. Tumor targeting effect was robust
      even under a very low tumor cell to normal cell ratio and targeting efficiency
      correlated with NKG2D ligand expression level on tumor cells. Furthermore, the
      magnetic separation platform utilized to test NKG2D/NP specificity has the
      potential to be developed into high throughput screening strategies to identify
      ideal fusion proteins or antibodies for targeting IONPs. In conclusion, NKG2D/NPs
      can be used to target multiple tumor types and magnetic separation platform can
      facilitate the proof-of-concept phase of tumor targeting IONP development. 

PMID- 25371537
TI  - Case-only exome sequencing and complex disease susceptibility gene discovery:
      study design considerations.
AB  - Whole exome sequencing (WES) provides an unprecedented opportunity to identify
      the potential aetiological role of rare functional variants in human complex
      diseases. Large-scale collaborations have generated germline WES data on patients
      with a number of diseases, especially cancer, but less often on healthy controls
      under the same sequencing procedures. These data can be a valuable resource for
      identifying new disease susceptibility loci if study designs are appropriately
      applied. This review describes suggested strategies and technical considerations
      when focusing on case-only study designs that use WES data in complex disease
      scenarios. These include variant filtering based on frequency and functionality,
      gene prioritisation, interrogation of different data types and targeted
      sequencing validation. We propose that if case-only WES designs were applied in
      an appropriate manner, new susceptibility genes containing rare variants for
      human complex diseases can be detected. 

PMID- 25371539
TI  - CRL4DCAF1 is required in activated oocytes for follicle maintenance and
      ovulation.
AB  - In mammals, oocytes within the primordial follicles require a number of essential
      factors to maintain their survival. However, the survival factors for activated
      oocytes have been poorly characterized. Recently we reported that damaged DNA
      binding protein-1 (DDB1), the linker subunit of the cullin ring-finger ubiquitin
      E3 ligase-4 (CRL4) complex, and its substrate adaptor, DDB1-CUL4 associated
      factor-1 (DCAF1), were essential for primordial follicle maintenance. In this
      study we specifically deleted these in the oocytes of growing follicles, to
      investigate if DDB1 and DCAF1 were also survival factors for activated oocytes.
      In the ovaries of Ddb1(fl/fl);Zp3-Cre mice, the primordial follicle pool was
      intact, but awakened oocytes and growing follicles beyond the primary stage were
      rapidly depleted. In the ovaries of Dcaf1(fl/fl);Pten(fl/fl);Gdf9-Cre and
      Ddb1(fl/fl);Pten(fl/fl);Gdf9-Cre mice, global primordial follicle activation was
      stimulated by enhanced PI3K signaling, but the awakened oocytes were rapidly lost
      due to no CRL4(DCAF1) activity. These mouse models provided original evidence
      that CRL4(DCAF1) was essential for maintaining oocyte survival, not only those in
      dormancy at the primordial follicle stage, but also naturally awakened oocytes
      and those awakened by hyper-activation of PI3K signaling. Interestingly, the
      oocyte-specific Ddb1 or Dcaf1 knockout mice had ovulation defects even before
      oocyte exhaustion. CRL4(DCAF1) within oocytes was required for cumulus expansion
      and ovulation-related somatic gene expression in a cell non-autonomous manner.
      Granulosa cells that surrounded these Ddb1 or Dcaf1-deleted oocytes exhibited
      increased rates of apoptosis and showed poor responses to ovulation signals.
      These results suggested that CRL4 in oocytes also regulated granulosa cell
      functions in a cell non-autonomous manner. 

PMID- 25371540
TI  - Liver immune responses to inflammatory stimuli in a diet-induced obesity model of
      zebrafish.
AB  - Obesity- and metabolic syndrome-related diseases are becoming important medical
      challenges for the western world. Non-alcoholic fatty liver disease (NAFLD) is a
      manifestation of these altered conditions in the liver, and inflammation appears
      to be a factor that is tightly connected to its evolution. In this study, we used
      a diet-induced obesity approach in zebrafish (Danio rerio) based on overfeeding
      to analyze liver transcriptomic modulation in the disease and to determine how
      obesity affects the immune response against an acute inflammatory stimulus such
      as lipopolysaccharide (LPS). Overfed zebrafish developed an obese phenotype,
      showed signs of liver steatosis, and its modulation profile resembled that
      observed in humans, with overexpression of tac4, col4a3, col4a5, lysyl oxidases,
      and genes involved in retinoid metabolism. In response to LPS, healthy fish
      exhibited a typical host defense reaction comparable to that which occurs in
      mammals, whereas there was no significant gene modulation when comparing
      expression in the liver of LPS-stimulated and non-stimulated obese zebrafish at
      the same statistical level. The stimulation of obese fish represents a double-hit
      to the already damaged liver and can help understand the evolution of the
      disease. Finally, a comparison of the differential gene activation between
      stimulated healthy and obese zebrafish revealed the expected difference in the
      metabolic state between healthy and diseased liver. The differentially modulated
      genes are currently being studied as putative new pathological markers in NAFLD
      stimulated liver in humans. 

PMID- 25371541
TI  - Real-time decision support to guide percutaneous coronary intervention bleeding
      avoidance strategies effectively changes practice patterns.

PMID- 25371543
TI  - Mobile Mammography, Race, and Insurance: Use Trends Over a Decade at a
      Comprehensive Urban Cancer Center.
AB  - PURPOSE: To assess the use of a mobile mammography unit (MMU) as it relates to
      race and insurance status in the largest county in Kentucky. METHODS: We
      retrospectively reviewed 48,324 screening mammograms of 21,857 patients conducted
      over a 10-year period. Descriptive statistics for patient age, race, and
      insurance status were computed by entire cohort and within subsets of cohorts.
      This analysis was limited to trends in use by race and insurance status. To study
      the patterns of frequency distributions, indiscrete variables were performed
      using the Pearson chi(2) test. For continuous variable range, a 95% CI of mean
      was estimated. Comparisons with a P value less than .05 were considered
      statistically significant. RESULTS: Self-reported blacks constituted significant
      use of the MMU (29% v census data demographic reports of 19%). Race significantly
      correlated with likelihood to screen >= three times, with blacks (30.5%) more
      likely, and whites (27.8%) and Hispanics (20.2%) less likely (P < .001).
      Insurance status also affected frequency of use (P < .001). CONCLUSION: In this
      data set, blacks were more likely to repeat use of the MMU. Although preliminary,
      these data suggest outreach efforts of mobile mammography are appropriately
      reaching certain targeted populations.

PMID- 25371542
TI  - Culprit vessel versus multivessel intervention at the time of primary
      percutaneous coronary intervention in patients with ST-segment-elevation
      myocardial infarction and multivessel disease: real-world analysis of 3984
      patients in London.
AB  - BACKGROUND: It is estimated that up to two thirds of patients presenting with ST
      segment-elevation myocardial infarction have multivessel disease. The optimal
      strategy for treating nonculprit disease is currently under debate. This study
      provides a real-world analysis comparing a strategy of culprit-vessel
      intervention (CVI) versus multivessel intervention at the time of primary
      percutaneous coronary intervention in patients with ST-segment-elevation
      myocardial infarction. METHODS AND RESULTS: We compared CVI versus multivessel
      intervention in 3984 patients with multivessel disease undergoing primary
      percutaneous coronary intervention between 2004 and 2011 at all 8 tertiary
      cardiac centers in London. Multivariable-adjusted models were built to determine
      independent predictors for in-hospital major adverse cardiovascular events
      (MACEs) and all-cause mortality at 1 year. To reduce confounding and bias,
      propensity score methods were used. CVI was associated with reduced in-hospital
      MACE (4.6% versus 7.2%; P=0.010) and mortality at 1 year (7.4% versus 10.1%;
      P=0.031). CVI was an independent predictor for reduced in-hospital MACE (odds
      ratio, 0.49; 95% confidence interval [CI], 0.32-0.75; P<0.001) and survival at 1
      year (hazard ratio, 0.65; 95% CI, 0.47-0.91; P=0.011) in the complete cohort; and
      in 2821 patients in propensity-matched cohort (in-hospital MACE: odds ratio,
      0.49; 95% CI, 0.32-0.76; P=0.002; and 1-year survival: hazard ratio, 0.64; 95%
      CI, 0.45-0.90; P=0.010). Inverse probability treatment weighted analyses also
      confirmed CVI as an independent predictor for reduced in-hospital MACE (odds
      ratio, 0.38; 95% CI, 0.15-0.96; P=0.040) and survival at 1 year (hazard ratio,
      0.44; 95% CI, 0.21-0.93; P=0.033). CONCLUSIONS: In this observational analysis of
      patients with ST-segment-elevation myocardial infarction undergoing primary
      percutaneous coronary intervention, CVI was associated with increased survival at
      1 year. Acknowledging the limitations with observational analyses, our findings
      support current recommended practice guidelines.

PMID- 25371544
TI  - Blue skies for the best people.

PMID- 25371545
TI  - Actions speak much louder than words: for midcareer and senior investigators, the
      track record of productivity should be paramount in selecting grant recipients.

PMID- 25371546
TI  - The fungus, the witches' broom, and the chocolate tree: deciphering the molecular
      interplay between Moniliophthora perniciosa and Theobroma cacao.

PMID- 25371549
TI  - Complementary effects of gaze direction and early saliency in guiding fixations
      during free viewing.
AB  - Gaze direction provides an important and ubiquitous communication channel in
      daily behavior and social interaction of humans and some animals. While several
      studies have addressed gaze direction in synthesized simple scenes, few have
      examined how it can bias observer attention and how it might interact with early
      saliency during free viewing of natural and realistic scenes. Experiment 1 used a
      controlled, staged setting in which an actor was asked to look at two different
      objects in turn, yielding two images that differed only by the actor's gaze
      direction, to causally assess the effects of actor gaze direction. Over all
      scenes, the median probability of following an actor's gaze direction was higher
      than the median probability of looking toward the single most salient location,
      and higher than chance. Experiment 2 confirmed these findings over a larger set
      of unconstrained scenes collected from the Web and containing people looking at
      objects and/or other people. To further compare the strength of saliency versus
      gaze direction cues, we computed gaze maps by drawing a cone in the direction of
      gaze of the actors present in the images. Gaze maps predicted observers' fixation
      locations significantly above chance, although below saliency. Finally, to gauge
      the relative importance of actor face and eye directions in guiding observer's
      fixations, in Experiment 3, observers were asked to guess the gaze direction from
      only an actor's face region (with the rest of the scene masked), in two
      conditions: actor eyes visible or masked. Median probability of guessing the true
      gaze direction within +/-9 degrees  was significantly higher when eyes were
      visible, suggesting that the eyes contribute significantly to gaze estimation, in
      addition to face region. Our results highlight that gaze direction is a strong
      attentional cue in guiding eye movements, complementing low-level saliency cues,
      and derived from both face and eyes of actors in the scene. Thus gaze direction
      should be considered in constructing more predictive visual attention models in
      the future. 

PMID- 25371547
TI  - High-resolution transcript profiling of the atypical biotrophic interaction
      between Theobroma cacao and the fungal pathogen Moniliophthora perniciosa.
AB  - Witches' broom disease (WBD), caused by the hemibiotrophic fungus Moniliophthora
      perniciosa, is one of the most devastating diseases of Theobroma cacao, the
      chocolate tree. In contrast to other hemibiotrophic interactions, the WBD
      biotrophic stage lasts for months and is responsible for the most distinctive
      symptoms of the disease, which comprise drastic morphological changes in the
      infected shoots. Here, we used the dual RNA-seq approach to simultaneously assess
      the transcriptomes of cacao and M. perniciosa during their peculiar biotrophic
      interaction. Infection with M. perniciosa triggers massive metabolic
      reprogramming in the diseased tissues. Although apparently vigorous, the infected
      shoots are energetically expensive structures characterized by the induction of
      ineffective defense responses and by a clear carbon deprivation signature.
      Remarkably, the infection culminates in the establishment of a senescence process
      in the host, which signals the end of the WBD biotrophic stage. We analyzed the
      pathogen's transcriptome in unprecedented detail and thereby characterized the
      fungal nutritional and infection strategies during WBD and identified putative
      virulence effectors. Interestingly, M. perniciosa biotrophic mycelia develop as
      long-term parasites that orchestrate changes in plant metabolism to increase the
      availability of soluble nutrients before plant death. Collectively, our results
      provide unique insight into an intriguing tropical disease and advance our
      understanding of the development of (hemi)biotrophic plant-pathogen interactions.

PMID- 25371548
TI  - Brassinosteroid regulates cell elongation by modulating gibberellin metabolism in
      rice.
AB  - Brassinosteroid (BR) and gibberellin (GA) are two predominant hormones regulating
      plant cell elongation. A defect in either of these leads to reduced plant growth
      and dwarfism. However, their relationship remains unknown in rice (Oryza sativa).
      Here, we demonstrated that BR regulates cell elongation by modulating GA
      metabolism in rice. Under physiological conditions, BR promotes GA accumulation
      by regulating the expression of GA metabolic genes to stimulate cell elongation.
      BR greatly induces the expression of D18/GA3ox-2, one of the GA biosynthetic
      genes, leading to increased GA1 levels, the bioactive GA in rice seedlings.
      Consequently, both d18 and loss-of-function GA-signaling mutants have decreased
      BR sensitivity. When excessive active BR is applied, the hormone mostly induces
      GA inactivation through upregulation of the GA inactivation gene GA2ox-3 and also
      represses BR biosynthesis, resulting in decreased hormone levels and growth
      inhibition. As a feedback mechanism, GA extensively inhibits BR biosynthesis and
      the BR response. GA treatment decreases the enlarged leaf angles in plants with
      enhanced BR biosynthesis or signaling. Our results revealed a previously unknown
      mechanism underlying BR and GA crosstalk depending on tissues and hormone levels,
      which greatly advances our understanding of hormone actions in crop plants and
      appears much different from that in Arabidopsis thaliana. 

PMID- 25371550
TI  - Mealtime dynamics in child feeding disorder: the role of child temperament,
      parental sense of competence, and paternal involvement.
AB  - OBJECTIVE: We examined how child temperament, parental sense of competence, and
      paternal involvement predicted observed mealtime dynamics. METHOD: 97 families of
      children with feeding disorder (FD), sleep problems (SP), and typically
      developing (TD) children participated in the study. Data were collected during
      home visits, where mother-child and father-child mealtime dynamics were
      videotaped and parents completed questionnaires. RESULTS: More mother-child and
      father-child conflict and control was observed during mealtimes in the FD than SP
      and TD groups. Among the FD group, maternal sense of competence was negatively
      correlated with mother-child conflict and control, and child temperament was
      linked to father-child conflict and control, but only for families in which
      fathers were highly involved. These correlations were not significant among the
      SP and TD groups. CONCLUSION: Different patterns of results were seen for mothers
      and fathers and among the FD and control groups. Clinical implications for the
      treatment of FD are discussed.

PMID- 25371551
TI  - Efficient generation of marker-free transgenic rice plants using an improved
      transposon-mediated transgene reintegration strategy.
AB  - Marker-free transgenic plants can be developed through transposon-mediated
      transgene reintegration, which allows intact transgene insertion with defined
      boundaries and requires only a few primary transformants. In this study, we
      improved the selection strategy and validated that the maize (Zea mays)
      Activator/Dissociation (Ds) transposable element can be routinely used to
      generate marker-free transgenic plants. A Ds-based gene of interest was linked to
      green fluorescent protein in transfer DNA (T-DNA), and a green fluorescent
      protein-aided counterselection against T-DNA was used together with polymerase
      chain reaction (PCR)-based positive selection for the gene of interest to screen
      marker-free progeny. To test the efficacy of this strategy, we cloned the
      Bacillus thuringiensis (Bt) delta-endotoxin gene into the Ds elements and
      transformed transposon vectors into rice (Oryza sativa) cultivars via
      Agrobacterium tumefaciens. PCR assays of the transposon empty donor site
      exhibited transposition in somatic cells in 60.5% to 100% of the rice
      transformants. Marker-free (T-DNA-free) transgenic rice plants derived from
      unlinked germinal transposition were obtained from the T1 generation of 26.1% of
      the primary transformants. Individual marker-free transgenic rice lines were
      subjected to thermal asymmetric interlaced-PCR to determine Ds(Bt) reintegration
      positions, reverse transcription-PCR and enzyme-linked immunosorbent assay to
      detect Bt expression levels, and bioassays to confirm resistance against the
      striped stem borer Chilo suppressalis. Overall, we efficiently generated marker
      free transgenic plants with optimized transgene insertion and expression. The
      transposon-mediated marker-free platform established in this study can be used in
      rice and possibly in other important crops. 

PMID- 25371553
TI  - Core concepts: quasiparticle.

PMID- 25371552
TI  - Involvement of the electrophilic isothiocyanate sulforaphane in Arabidopsis local
      defense responses.
AB  - Plants defend themselves against microbial pathogens through a range of highly
      sophisticated and integrated molecular systems. Recognition of pathogen-secreted
      effector proteins often triggers the hypersensitive response (HR), a complex
      multicellular defense reaction where programmed cell death of cells surrounding
      the primary site of infection is a prominent feature. Even though the HR was
      described almost a century ago, cell-to-cell factors acting at the local level
      generating the full defense reaction have remained obscure. In this study, we
      sought to identify diffusible molecules produced during the HR that could induce
      cell death in naive tissue. We found that 4-methylsulfinylbutyl isothiocyanate
      (sulforaphane) is released by Arabidopsis (Arabidopsis thaliana) leaf tissue
      undergoing the HR and that this compound induces cell death as well as primes
      defense in naive tissue. Two different mutants impaired in the pathogen-induced
      accumulation of sulforaphane displayed attenuated programmed cell death upon
      bacterial and oomycete effector recognition as well as decreased resistance to
      several isolates of the plant pathogen Hyaloperonospora arabidopsidis. Treatment
      with sulforaphane provided protection against a virulent H. arabidopsidis
      isolate. Glucosinolate breakdown products are recognized as antifeeding compounds
      toward insects and recently also as intracellular signaling and bacteriostatic
      molecules in Arabidopsis. The data presented here indicate that these compounds
      also trigger local defense responses in Arabidopsis tissue. 

PMID- 25371555
TI  - Iterative reconstruction using a Monte Carlo based system transfer matrix for
      dedicated breast positron emission tomography.
AB  - To maximize sensitivity, it is desirable that ring Positron Emission Tomography
      (PET) systems dedicated for imaging the breast have a small bore. Unfortunately,
      due to parallax error this causes substantial degradation in spatial resolution
      for objects near the periphery of the breast. In this work, a framework for
      computing and incorporating an accurate system matrix into iterative
      reconstruction is presented in an effort to reduce spatial resolution degradation
      towards the periphery of the breast. The GATE Monte Carlo Simulation software was
      utilized to accurately model the system matrix for a breast PET system. A
      strategy for increasing the count statistics in the system matrix computation and
      for reducing the system element storage space was used by calculating only a
      subset of matrix elements and then estimating the rest of the elements by using
      the geometric symmetry of the cylindrical scanner. To implement this strategy,
      polar voxel basis functions were used to represent the object, resulting in a
      block-circulant system matrix. Simulation studies using a breast PET scanner
      model with ring geometry demonstrated improved contrast at 45% reduced noise
      level and 1.5 to 3 times resolution performance improvement when compared to MLEM
      reconstruction using a simple line-integral model. The GATE based system matrix
      reconstruction technique promises to improve resolution and noise performance and
      reduce image distortion at FOV periphery compared to line-integral based system
      matrix reconstruction.

PMID- 25371556
TI  - Effect of Euphorbia cyparissias ointments on acanthosis.
AB  - BACKGROUND: A pharmaco-chemical investigation of the Euphorbia cyparissias plant
      was justified by its known multiple therapeutic valences. Numerous components
      from extracts and latex of Euphorbiacae were identified, revealing a large plant
      family with a polyvalent therapeutic activity. MATERIALS AND METHODS: The aim of
      the study was to assess the skin tolerance level to irritation on different
      testing concentrations, of Euphorbia cyparissias extracts and ointments. Study
      was accomplished in rats and dogs, with the identification of all possible skin
      injuries and histological changes, after a simple patch test methodology.
      RESULTS: Ointment dermatological testing on rats, proved to be bearable on
      epilated skin at concentrations of 1, 2 and 5%. Ointments and mother tincture
      with higher concentrations (10% and 20%), led to irritation and cutis damages,
      and this was revealed through histology. CONCLUSION: Ointment tested on dog's
      skin was tolerable for epilated skin to concentrations of 1, 2 and/or 5%,
      additional testing on human volunteers confirmed the same situation.

PMID- 25371557
TI  - Total anti-oxidant capacity, flavonoid, phenolic acid and polyphenol content in
      ten selected species of Zingiberaceae rhizomes.
AB  - BACKGROUND: Natural products such as herbs, fruits, spices, beverages, vegetables
      are becoming more popular among scientific community and consumers because of
      their potential to arrest the effect of free radicals in human system. This study
      determined the total antioxidant capacity of ten selected species of
      Zingiberaceae (Ginger) used as spices and for medicinal purposes in Southeast
      Asia. MATERIALS AND METHODS: Methanol was used as the extraction solvent, 2,2 -
      diphenyl-1-picrylhydrazil (DPPH) for free radical scavenging activity and ferric
      reducing antioxidant power (FRAP) assays. Phenolic compounds were measured using
      Total flavonoid, Phenolic acid and Polyphenols content assay to evaluate the
      quality of the antioxidant capacity of the rhizomes and vitamin C as positive
      control. RESULTS: The results obtained revealed that Curcuma longa and Zingiber
      officinale had the highest free radical scavenging capacity of 270.07mg/TE/g DW
      and 266.95mg/TE/g DW and FRAP assay, Curcuma longa and Zingiber officinale also
      gave the highest ferric reducing power of 231.73mg/TE/g DW and 176.26mg/TE/g DW
      respectively. For Phenolic compounds, Curcuma longa and Curcuma xanthorrhiza gave
      the highest values of flavonoid (741.36mg/NGN/g DW and 220.53mg/NGN/g DW),
      phenolic acid (42.71mg/GAE/g DW and 22.03mg/GAE/g DW) and polyphenols
      (39.38mg/GAE/g DW and 38.01mg/GAE/g DW) respectively. Significant and positive
      linear correlations were found between Total antioxidant capacity and Phenolic
      compounds (R = 0.65 - 0.96). CONCLUSION: This study provides evidence that
      extracts of Zingiberaceae (Ginger) rhizomes are a potential source of natural
      antioxidants and could serve as basis for future drugs and food supplements.

PMID- 25371558
TI  - Morin, a flavonoid, on lipid peroxidation and antioxidant status in experimental
      myocardial ischemic rats.
AB  - BACKGROUND: Myocardial infarction affects a large population in the world. Lipid
      peroxide metabolism plays an important role in the pathology of myocardial
      infarction. OBJECTIVE: The present study was designed to investigate the
      antioxidant potential of morin, a flavonoid in isoproterenol (ISO)-induced
      myocardial infarction (MI), in rats. MATERIALS AND METHODS: Male albino Wistar
      rats were pre-treated with morin (40 mg/kg), daily for a period of 30 days. After
      the treatment period, ISO (85 mg/kg), was subcutaneously injected in rats at an
      interval of 24 h for 2 days. RESULTS: ISO-administered rats showed elevated
      levels of thiobarbituric acid reactive substances (TBARS), and lipid hydro
      peroxide (LOOH), in plasma and heart. Pretreatment with morin, the above changes
      were significantly reduced to near normal level. ISO-administered rats showed
      decrease in the activities of superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in heart. In
      addition, decrease the levels non enzymatic antioxidants such as reduced
      glutathione (GSH), vitamin C and vitamin E in plasma and heart while
      ceruloplasmin in plasma. CONCLUSION: Pretreatment with morin, reversed these
      above biochemical changes towards normalcy. These findings revealed that, the
      morin possess antioxidant activity in experimentally induced cardiac toxicity.

PMID- 25371559
TI  - Physico-chemistry of geophagic soils ingested to relief nausea and vomiting
      during pregnancy.
AB  - BACKGROUND: Nausea and vomiting during pregnancy (NVP) is one of the most common
      symptoms experienced by most women during their first trimester of pregnancy. For
      some of these women, especially the more tribally and culturally oriented ones,
      soil ingestion is one of the remedies used to curb NVP. The aim of this study was
      to physico-chemically characterise selected geophagic soils from Cameroon and
      South Africa, ingested for the relief of NVP and to appraise their ability to
      meet the needs of geophagic individuals. MATERIALS AND METHODS: Thirteen
      geophagic soil samples (6 from Cameroon and 7 from South Africa) were obtained
      from traditional mine sites and physico-chemically characterized. The following
      tests were conducted; particle size distribution (PSD), liquid limit (LL),
      plastic limit (PL), plasticity index, soil pH and electrical conductivity (EC).
      RESULTS: The samples were texturally classified as silt loam, of medium to high
      plasticity with normal to active swelling potentials. The samples were generally
      acidic (pH of 3.1 - 6.1) with low EC (average of 92.71uS/cm). CONCLUSION: Based
      on soil consistency limits and pH, the samples were found to be suitable for use
      as remedy for NVP with soils from Cameroon displaying the most optimum
      properties.

PMID- 25371560
TI  - The neuroprotective effect of electro-acupuncture against ischemic stroke in
      animal model: a review.
AB  - BACKGROUND: It is well established that electro-acupuncture can exert
      neuroprotection in animal experiments. However, the exact mechanism of electro
      acupuncture against ischemic stroke is not very clear. MATERIALS AND METHODS:
      Literature retrieval was performed in four databases (OVID, PUBMED, EMBASE, and
      ISI Web of Science), from respective inception to July 2013. RESULTS: Series of
      studies have demonstrated that electro-acupuncture might be a promising method in
      reducing brain damage after stroke and induce brain ischemic tolerance before
      stroke through the promotion of angiogenesis, alleviation of the inflammatory
      response, regulation of the blood brain barrier (BBB), inhibition of apoptosis,
      and so on. Through these mechanisms, electro-acupuncture may reduce the neural
      damages associated with stroke. CONCLUSION: An awareness of the benefits of
      acupuncture might lead more patients into accepting acupuncture therapy for the
      management of patients with ischemic stroke and patients with high risk of
      ischemic stroke.

PMID- 25371562
TI  - Investigation of total phenolic, total flavonoid, antioxidant and allyl
      isothiocyanate content in the different organs of Wasabi japonica grown in an
      organic system.
AB  - BACKGROUND: This study was carried out to investigate the total polyphenol (TP),
      total flavonoid (TF), antioxidative effect and allyl isothyocyanate (ITC) content
      in different organs of wasabi plant grown in an organic system. MATERIALS AND
      METHODS: Invitro study of methanol and boiled water extracts of wasabi were
      conducted by analyzing the 1-1-diphenyl-2-picryl hydrozyl (DPPH) radial
      scavenging activity, metal chelating activity and total antioxidant capacity in a
      comparative manner. RESULT: The result revealed that methanol extract showed
      higher TP in flower (3644 mg TAE/100 g dw), leaf (3201 mg TAE/100 g dw) and fruit
      (3025 mg TAE/100 g dw) as compared to the boiled water extract. Similarly, TF
      content was also higher in methanol extracts of flower (1152 mg QE/100 g dw) and
      leaf (325 mg QE/100 g dw), however, the other parts showed ignorable value.
      RESULTS: Results of antioxidant activity were found at different magnitude of
      potency. The methanol extract of different parts of wasabi exhibited higher
      activity in total antioxidant capacity and DPPH radical scavenging assay as
      compared to water extract. In metal chelating assay, the boiled water extracts of
      leaf showed higher (76.9%) activity, followed by fruit (68.8%) and flower
      (62.8%). Ally ITC detected by gas chromatography was present in all of the
      tissues of wasabi plant but the content was found to be varied in different
      tissues. CONCLUSIONS: Overall, this study will allow consumers and processors to
      understand the possibility for medical application of wasabi plant by knowing the
      level of total polyphenol distribution, Ally ITC content and antioxidant property
      distributed in different parts and tissues.Key words: Allyl ITC, antioxidant,
      flavonoid, polyphenol, Wasabi japonica.

PMID- 25371561
TI  - The mechanism of auriculotherapy: a case report based on the fractal structure of
      meridian system.
AB  - BACKGROUND: Chinese meridian system of acupuncture has recently been deciphered
      as the fractal continuum of neurovascular bundles and its smaller branches. The
      corresponding acupuncture mechanism of therapeutics has been attributed to the
      magneto-electric inductive effects of the meridian system via chaotic wave of
      nerve innervations and blood flow. Hence, based on the proposed theory, the
      important sensory organ of the ears should be able to exert its influence on
      visceral organs and peripheral limbs. This investigation aims to verify if such a
      possible correlation exists between an external region of the ear and the muscle
      of biceps brachii in the French auriculotherapy. MATERIALS AND METHODS: A region
      between the points of elbow and shoulder in the scaphoid fossa (upper arm), was
      chosen. Before the recording of surface electromyograms (EMGs), of the muscle of
      biceps brachii, two subjects were asked to carry out maximum voluntary isometric
      contractions (MVICs), of the arm. In addition, the same volunteers would be
      served as control group. Consequently, each subject was required to perform the
      three treatments of control, sham, and acupressure in random order. EMG signals
      were recorded for later analysis. RESULTS: Results indicate that the acupressure
      with finger at a specific point which bears possibly with a somatopic relation to
      the biceps brachii muscle can, in a man, modify the response of the EMGs
      associated with the corresponding muscle while the response of the acupressure of
      a sham point has different responses. Moreover, the MVIC parameters were higher
      in acupressure treatment than those of control and sham treatments for both
      subjects. CONCLUSION: In conclusion, the analysis of the findings permits us to
      speculate that the stimulation with the fingers in the scaphoid fossa of the ear
      presents electromyographic responses related to the biceps brachii muscle. Hence,
      the mechanism of French auriculotherapy could be derived from the same principle
      as that of the Chinese acupuncture.

PMID- 25371563
TI  - Antioxidant activity in vitro and hepatoprotective effect of Phlomis maximowiczii
      in vivo.
AB  - BACKGROUND: A number of medicinal plants and there compounds played a major role
      in the treatment of hepatic disorders. They were widely used for the treatment of
      these disorders, and oxidant stress injury was one of the liver injury
      mechanisms. The present study evaluated the antioxidant activity and the
      hepatoprotective effect of each extracts of Phlomis maximowiczii. MATERIALS AND
      METHODS: The antioxidant activity was assayed by the methods of ABTS, FRAP and
      DPPH in vitro. Hepatoprotective effect of P. maximowiczii extracts was examined
      using carbon tetrachloride-induced acute liver injury in mice. RESULTS: P.
      maximowiczii n-butanol (PMBU) extract, ABTS (IC50=18.96 ug/mL), DPPH (IC50=25.15
      ug/mL), and FRAP (RACT50=2775.6+/-144.18 umol/g), showed higher scavenging
      capacity than that of P. maximowiczii ethyl acetate (PMEA). The n-butanol extract
      could significantly reduce the level of GPT, GOT and MDA (P<0.05, P<0.001 and
      P<0.001, respectively) and increase the level of SOD (P<0.001), respectively.
      CONCLUSION: The antioxidant activity of n-butanol extract in vitro was related
      with the level of MDA and SOD in vivo, and hepatoprotective effect of n-butanol
      extract also had relationship with its antioxidant activity in vivo.

PMID- 25371564
TI  - Effective chemical constituent's identification of extracting solution from herbs
      - a review.
AB  - BACKGROUND AND OBJECTIVE: The aim of this article, was the definition, and
      targets of possible mechanisms of Yin lai Decoction by retrieving the herbals in
      the decoction and integrating information from multi-databases, which can be
      guidance for the followed experimental study. MATHERIALS AND METHODS: The
      information from multi-databases was integrated. RESULTS: In the study, we
      discovered 92 possible gene targets of Yin lai Decoction, 87% of which appeared
      in the targets of Flos Lonicerae, Fructus Forsythiae and Scutellaria baicalensis
      Georgi. The function of these targets focuses on the anti-infection and
      regulating immune system, and metabolism of the body. CONCLUSION: Yin lai
      Decoction may affect the process of metabolism, immune response and infection by
      impact on the 92 possible gene targets, then it can mitigate the damage caused by
      infection and promote the body to health. But the definite mechanisms must be
      explored by further experimental study.

PMID- 25371565
TI  - Volatiles of Lysimachia paridiformis Var. Stenophylla, Lysimachia fortumei and
      Lysimachia chikungensis by HS-SPME-GC-MS.
AB  - BACKGROUND: Lysimachia paridiformis Var. Stenophylla mainly contain flavonoid
      constituents. Flavonoids and benzoquinones are the main compounds in L. fortumei
      Maxim. The objective of this paper was to study the volatile compounds of leaves
      in L. paridiformis Var. Stenophylla, L. fortumei and L. chikungensis for the
      first time. MATERIALS AND METHODS: Volatiles were extracted by the manual solid
      phase micro-extraction (SPME). The volatile constituents were analyzed by an
      Agilent 6890 N gas chromatograph equipped and coupled with a 5975B mass selective
      detector spectrometer. RESULTS: Twenty-nine compounds were identified in the
      leaves of L. paridiformis var. Stenophylla, accounting for 89.17% of the total
      volatile fraction. The main constituents were ethanol (13.58%), and beta-ionone
      (8.05%). linalool and beta-ionone were the main aroma constituents in L.
      paridiformis var. Stenophylla. Twenty-one compounds were identified in the leaves
      of L. fortumei, accounting for 94.72% of the total volatile fraction. The main
      constituents were tricosane (14.72%), docosane (11.02%), tetracosane (10.77%) and
      pentacosane (9.81%). Thirty-two compounds were identified in the leaves of L.
      chikungensis, accounting for 88.58% of the total volatile fraction. Typical
      compounds detected in L. chikungensis were cis-3-hexenyl pentanoate (13.33%),
      followed by ethanol (12.13%), ethyl palmitate (7.78%), and heneicosane (5.38%).
      CONCLUSION: The results showed that the main composition types were similar in
      the three plants, but the content was different, which indicated that the similar
      composition types provided the same medical effect for three plants.

PMID- 25371566
TI  - Bioactive compounds and encapsulation of Yanang (Tiliacora triandra) leaves.
AB  - BACKGROUND: Yanang (Tiliacora triandra) has been known as vegetable and herbal in
      northeast Thailand and Lao People's Democratic Republic. Extracts from Yanang
      leaves contain high amounts of polyphenol constituents possessing antioxidant
      activity. MATERIALS AND METHODS: This work investigated bioactive compounds of
      Yanang extracts prepared by infusion with water, ethanol and acetone.
      Furthermore, this paper reports the design of the experimental method for
      optimization of Yanang encapsulation using three independent variables: the ratio
      of core material (Yanang), to wall material (gum Arabic), gum Arabic
      concentration and inlet temperature of spray drying on bioactive compounds
      stability. The stability of bioactive compounds was evaluated using phenolic
      compounds, total antioxidant, carotenoids and chlorophyll. RESULTS: The study of
      the bioactivity of Yanang extracts found that extraction with water was the
      appropriate application. The study of Yanang encapsulation demonstrated that gum
      Arabic, as coating agents, protected bioactive compounds of Yanang. Optimized
      condition for the encapsulation was at the ratio of core to wall {1:4}, in gum
      Arabic concentration 10% (w/v), and inlet temperature at 160?C. The results show
      that the bioactive compounds were mainly affected by the ratio of core to wall
      material. Besides, moisture content and particle size of encapsulation depend on
      inlet temperature of spray drying, and gum Arabic concentration, respectively.
      This optimization reveals that the encapsulation process did not lose the
      bioactive compounds. CONCLUSION: Yanang extract with water was the main phenolic
      compound and showed high antioxidant activities. This study demonstrates the
      potentials of using spray drying process and optimization for the encapsulation
      of herbal products.

PMID- 25371567
TI  - Antioxidant activities in vitro and hepatoprotective effects of Nelumbo nucifera
      leaves in vivo.
AB  - BACKGROUND: Herbal medicines played a major role in the treatment of hepatic
      disorders, and a number of medicinal plants and their compounds were widely used
      for the treatment of these disorders, and oxidant stress injury was one of the
      mechanism of liver injury. MATERIALS AND METHODS: Antioxidant activity of Nelumbo
      nucifera leaves (NU) extracts was assayed by the methods of scavenging 1,1
      diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzo-thiazoline-6
      sulfonicacid) (ABTS) radical and ferric reducing antioxidant power (FRAP) in
      vitro. By intraperitoneal injection carbon tetrachloride (CCl4) to establish
      acute liver injury model in mice, the levels of Glutamic-pyruvic transaminase
      (GPT), glutamic-oxaloacetic transaminase (GOT), superoxide dismutase (SOD) and
      the content of and maleicdialdehyde (MDA) were detected to evaluate
      hepatoprotective effect of NU using corresponding test kit. RESULTS: EtOAC (NUEA)
      and n-BuOH extracts (NUBU) of N. nucifera leaves had good scavenging DPPH and
      ABTS radical activity and ferric reducing antioxidant power in vitro. DPPH
      radical scavenging activity and ferric reducing antioxidant power of NUEA (IC50=
      6.68+/-0.29 ug/mL, RACT50=1749.82+/-67.03 umol/g) and NUBU (IC50= 4.61+/-0.01
      ug/mL, RACT50=1995.27+/-135.71 umol/g ) were higher than that of BHT (IC50=8.76+/
      0.20 ug/mL, RACT50=1581.68+/-97.41 umol/g) and Dangfeiliganning (IC50=28.06+/
      0.17 ug/mL, RACT50=1028.55+/-3.28 umol/g). ABTS radical scavenging activity of
      NUEA (IC50= 5.32+/-0.12 ug/mL) and NUBU (IC50= 8.16+/-0.27 ug/mL) were higher
      than that of Dangfeiliganning (IC50= 9.76+/-0.16 ug/mL). Thus, hepatoprotective
      effect of NUEA and NUBU was evaluated on CCl4-induced acute liver injury mice.
      The results showed that the levels of GOT and GPT in each treatment group
      significantly decreased (p<0.001 and p<0.01, p<0.05, respectively) except for the
      group of NUEA (130.8 mg/kg) (p>0.05). The contents of malondialdehyde (MDA) in
      liver in groups of NUEA (523 mg/kg), NUBU (840.5 and 420.5 mg/kg, repectively)
      had significant decrease (p<0.001 and p<0.05, respectively), and the level of SOD
      in liver for each treatment group could significantly decrease (p<0.001, p<0.05,
      respectively). CONCLUSION: NUEA and NUBU had significantly hepatoprotective
      effect for Calcium tetrachloride CCl4-induced liver injury, which might be
      attributable to its antioxidant activity.

PMID- 25371568
TI  - Astragalus mongholicus regulate the Toll-like-receptor 4 meditated signal
      transduction of dendritic cells to restrain stomach cancer cells.
AB  - BACKGROUND: According to the traditional view, we depend on three methods to
      treat tumors; surgery, chemotherapy and radiotherapy. However, these methods have
      its own limitations in application. Traditional Chinese Medicine (TCM) is one of
      the oldest healing systems. Astragalus mongholicus (AMs) that is the common
      herbal medicine, the biggest part of TCM, have been proved to be effective in
      treating cancers from lots of clinical cases. However, we have not fully
      understood the anti-tumor mechanism of AMs, and this has lead to some doubt for
      some Western-Medicine scholars and restricts its wide use. The main objective of
      this research is to discuss the effect and mechanism of AMs to human stomach
      cancer. MATERIALS AND METHODS: To observe the effect and mechanism of tumor
      treatment by AMs, we have done the research from three major aspects, the
      influence of DCs, the inhibition of tumor in vitro as well as the animal studies
      in vivo after treatment. First, we culture the mouse dendritic cells (DCs) from
      bone marrow of mouse hind legs according to the method using Interleukin-4(IL-4)
      and Granulocyte-macrophage colony stimulating factor (GM-CSF), which refer to the
      way established by Inaba (Inaba K, 1992). And then we investigate the growth-rate
      of the DCs co-cultured with AMs injection. We analyze the expression of the Toll
      like-receptor 4 (TLR4), with SYBR-Green I Real-time PCR and the I-kappa-B-alpha
      (IkappaB-alpha) with Western-Blot, the main regulatory protein to control nuclear
      factor NFkappaB-p65 nuclear translocation. Second, we choose the human gastric
      cancer cell lines MKN 45 as the target cell, which was co-cultured with DCs, T
      cells from spleen of mouse and AMs injection, and use MTT assay to judge the
      amount of cell lines and Immnunoflurescene to analyze the expression of anti
      active caspase 3 pAb anti-PARP P85 fragment pAb, the mark of apoptosis of cells.
      Third, we have conducted the animal studies beside the basic experiment in vitro.
      The nude mouse developed stomach cancer, due to intra-preritoneal injection with
      MKN45 have been divided into two groups: the treatment group challenged with AMs
      injection and the control group with saline injection. We took the average of the
      diameter of each group as the y axis and the days after administered with AMs as
      x axis. After 40 days, all animals were killed by detruncation, and the tumor
      were removed and measured. We compare the diameter (<40 days) and weight (>40
      days) of the tumor as well as the survival days between different groups to
      investigate the effect of inhibition of cancer. RESULTS: All results show that
      AMs is effective in treating human stomach cancer and the mechanism might be
      regulated by TLR4 mediated signal transduction of DCs. The results are briefly
      introduced as follows: First, we succeed in culturing the DCs induced by IL-4 and
      GM-CSF and find the positive rate of CD11c expression, the mark of DCs, is beyond
      90% (Fig-1). We detect AMs can precipitate DCs maturation by upregulating TLR4 in
      SYBR-Green I Real-time PCR (Fig-2) and suppressing I.B-aby Western-Blot (Fig-3).
      Second, after the MKN45 co-cultured with DCs, T cells and AMs injection, the
      result show that AMs can great reduce the amount of cell lines by MTT assay (Fig
      4) and induce apoptosis with Immunofluorescence (Fig-5). Finally, we have
      conducted animal studies beside the experiment in vitro, and the result in vivo
      show that AMs can delay tumor development from the diameter and weight of the
      tumor (Fig-6, Fig-7), prolong life-span and improve life-quality. Figure 1the
      morphology and phenotypic identification of DCs.The form of DCs observed by
      microscope with field 20*.The isotype antibody control using FCM.The positive
      rate of CD11c expression.Figure 2the melting curve and the chart of TLR4
      expressiona) the melting curve of beta-actin; b)the melting curve of TLR4;c)the
      TLR4 expression of DCs stimulated with AM at different dose. There is significant
      statistic difference between the 60ng/mL and 80ng/mL group and other group
      (P<0.05 by rank test)Figure 3the IkappaB-alpha expression of DCs with different
      dose of AMsL0: 0ng/mL; L1:20ng/mL; L2:40ng/mL; L3:60ng/mL; L4:80ng/mLFigure 4MTT
      assay to analyse the viability and proliferation of the two cell lines (P<0.05
      between the group with the dose of 60ng/mL and 80ng/mL and other group). the
      horizontal axis is the group treated with AM and saline at different dose, the
      vertical axis is the cell number.Figure 5the anti-active caspase-3 pAb (a) and
      anti-PARP P85 fragment pAb (b) actived by immunofluorescence.The cell mix were
      treated with 100uL anti-active caspase-3 pAb at a 1:250 dilution and anti-PARP
      P85 fragment pAb at a 1:100 dilution, and the secondary Ab was donkey anti-rabbit
      Cy(r)3 conjugate diluted 1:500 in PBS (Jackson Cat#711-165-152). From the photo,
      we find that anti-active caspase-3 pAb and anti-PARP P86 fragment pAb can express
      which is very important to indicate cell-apoptosis.Figure 6The difference of
      tumor between treatment group and control group. CONCLUSION: Ams Can play a great
      role in treating human stomach cancers as a good Chinese herbal medicine by
      precipitating DCs maturation, which is probably due to its effects by regulating
      the TLR4 mediated signal transduction.

PMID- 25371569
TI  - Antioxidant and antibacterial activities of flavonoid glycosides from Ficus
      exasperata Vahl-Holl (moraceae) leaves.
AB  - BACKGROUND: Ficus exasperata Vahl-Holl (Moraceae) leaves are used for infectious
      and inflammatory conditions in many West African Countries. However, there is
      need for more phytochemical studies to justify the ethnomedicinal uses of the
      plant. MATERIAL AND METHODS: The crude 50% aqueous ethanolic extract of the
      leaves was partitioned successively between water and; n-hexane, ethyl acetate
      and n-butanol. The fractions were subjected to antimicrobial activity using agar
      diffusion test. n-Butanol fraction, which showed both antimicrobial and radical
      scavenging activities was subjected to repeated chromatographic fractionation on
      both silica and Sephadex LH-20 columns. Each stage of the purification was
      monitored by thin layer chromatographic diphenylpicryl hydrazyl autographic
      assay. Three compounds were isolated. The structures of the compounds were
      elucidated using spectroscopic methods, shift reagent studies, acid hydrolysis,
      and by comparison with literature data. RESULTS: The compounds were identified as
      apigenin C-8 glucoside (1), isoquercitrin-6-O-4-hydroxybenzoate (2) and quercetin
      3-O-beta-rhamnoside (3). The solvent fractions and isolated compounds were found
      to inhibit the growth of Gram +ve organisms only. CONCLUSION: These flavonoid
      glycosides are being reported in this plant species for the first time. Their
      weak in vitro antimicrobial activity suggest the flavonoids may be acting as pro
      drug. The radical scavenging activity of the compounds may justify some of the
      ethnomedicinal uses of the plant as free radicals are implicated in the aetiology
      of many inflammatory diseases.

PMID- 25371570
TI  - In vitro antioxidant and in vivo hepatoprotective activity of leave extract of
      Raphanus sativus in rats using CCL4 model.
AB  - BACKGROUND: Raphanus sativus is reported to have a variety of biological
      activities. This work screened the hepato-protective and antioxidant activity of
      ethanol (ERS), and aqueous (ARS), extracts of leaves of Raphanus sativus in
      Carbon tetrachloride (CCl4), model in rats. MATERIAL AND METHODS: The extracts
      were subjected to antioxidant tests (Total reducing power and Total phenolic
      content), and preliminary phytochemical screening. A pilot study was done on 100
      and 300 mg/kg extracts, form which 300 mg was chosen for further experiments. The
      albino rats (200-250 grams), were divided into 5 groups of 6 animals each (n=6).
      There were three control groups comprising of normal control (normal saline 
      1ml/kg), negative control group (CCl4 1ml/kg in olive oil in a ratio of 1:1 v/v),
      and positive control group (Silymarin 50mg/kg). The Test drugs were given in a
      dose of 300 mg/kg for both ERS and ARS extract for 7 days. Biochemical parameters
      (AST, ALT, Alkaline phosphatase, Total Bilirubin), histo-pathological examination
      of liver and in vivo antioxidant tests [CAT, GSH and MDA] were done. RESULTS: The
      phytochemical study showed the presence of flavanoids, terpenoids, alkaloids,
      saponins and sterols. A dose dependent increase in the oxidative potential was
      observed in both the extracts with total phenolic content 70.1 and 44.4 GAE/g
      extract for ERS and ARS respectively. ERS 300mg/kg showed a significant (p<0.001)
      increase in levels of AST, ALT and alkaline phosphatase as compared to negative
      control (percentage hepatoprotection =45.3%) while ARS 300 mg/kg (p<.01) group
      showed 30% hepatoprotection. The GSH (p<0.001) and CAT (p<0.05) in ERS and ARS
      were significantly increased while MDA levels were decreased (P< 0.01), as
      compared negative control. The findings were confirmed histo-pathological
      examination. CONCLUSION: The ethanol and aqueous extract of Raphanus sativus have
      partial hepatoprotection against CCl4 toxicity.

PMID- 25371571
TI  - Antioxidant activities and tyrosinase inhibition effects of Phaleria macrocarpa
      extracts.
AB  - BACKGROUND: The ethyl acetate and chloroform extracts of stems, leaves and fruits
      of Phaleria macrocarpa were screened for their antioxidant capacity and
      tyrosinase inhibition properties. MATERIAL AND METHOD: The total phenolic content
      (TPC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and ferric
      ion reducing power (FRAP) were used to evaluate their antioxidant capacity.
      Tyrosinase inhibition effect was measured using mushroom tyrosinase inhibition
      assay. RESULT: Ethyl acetate extract of P. macrocarpa's stem exhibited highest
      total phenolic content, DPPH free radical scavenging and ferric reducing power.
      Meanwhile, chloroform extracts of leaves and fruits demonstrated potent anti
      tyrosinase activities as compared to a well-known tyrosinase inhibitor, kojic
      acid. CONCLUSION: Since chloroform extracts of leaves and fruits have low
      antioxidant capacities, the tyrosinase inhibition effect observed are antioxidant
      independent. This study suggests direct tyrosinase inhibition by chloroform
      extracts of Phaleria macrocarpa.

PMID- 25371572
TI  - Effects of polysaccharides from Gynostemma pentaphyllum (Thunb.), Makino on
      physical fatigue.
AB  - BACKGROUND: Gynostemma pentaphyllum (Thunb.) Makino has been reported to have a
      wide range of health benefits in Chinese herbal medicines. Polysaccharides from
      Gynostemma pentaphyllum (PGP), has been identified as one of the active
      ingredients responsible for its biological activities. Although many
      pharmacological activities of PGP have received a great deal of attention, there
      is limited evidence for the anti-fatigue effects of PGP. The purpose of this
      study was to investigate the effects of polysaccharides from PGP on physical
      fatigue. MATERIALS AND METHOD: The rats were divided into four groups, with 10
      animals per group: control (C), group, low-treated (LT), group, medium-treated
      (MT), group, and high-treated (HT), group. The C group received distilled water,
      while LT, MT and HT groups were given various doses of PGP (100, 200, 400 mg/kg.
      d). After 30 days, forced swimming test was carried out in an acrylic plastic
      pool, then the exhaustive swimming time of rats and some biochemical parameters
      related to fatigue were measured. The data obtained showed that PGP could extend
      the exhaustive swimming time of the rats, as well as decrease the blood lactic
      acid (BLA), and blood urea nitrogen (BUN), concentrations, and increase the
      hemoglobin, liver glycogen and muscle glycogen concentrations. RESULT: The data
      obtained showed that different doses of PGP could extend the exhaustive swimming
      time of the rats, as well as decrease the BLA and BUN concentrations, and
      increase the hemoglobin, liver glycogen and muscle glycogen concentrations, which
      suggests that PGP had significant anti-fatigue effects on rats. CONCLUSION: PGP
      may be of use as a potential anti-fatigue agent, but there is a need for further
      research on long-term use in order to show its positive effects on physical
      fatigue.

PMID- 25371573
TI  - Carvacrol ameliorates the PPAR-A and cytochrome P450 expression on D
      galactosamine induced hepatotoxicity rats.
AB  - BACKGROUND: Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a predominant
      monoterpenic phenol which occurs in many essential oils of the family Labiatae
      including Origanum, Satureja, Thymbra, Thymus, and Corydothymus species. It is
      well known for its anti-inflammatory, antioxidant and antitumor activities. The
      present study investigates the influence of carvacrol on CYP2E1 and PPAR-alpha on
      D-Galactosamine (D-GalN)-induced hepatotoxic rats. MATERIALS AND METHODS: The
      mRNA and protein expression levels of CYP2E1 and PPAR-alpha have been assayed by
      semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and
      western blot analysis. RESULT: The result demonstrated that the mRNA and protein
      expressions of CYP2E1(p=0.012; p=0.015) significantly up-regulated while the mRNA
      and protein expressions of PPAR-alpha (p=0.026; p=0.03) significantly down
      regulated on D-galactosamine induced hepatotoxic rats and treatment with
      carvacrol significantly suppressed the mRNA and protein (CYP2E1, p=0.010;
      p=0.011) (PPAR-alpha, p=0.033; p=0.037) expressions of these genes. CONCLUSION:
      Thus, the present results have shown that carvacrol has the hepatoprotective
      effect and also alleviates liver damage associated with GalN induced hepatotoxic
      rats by down-regulating the CYP2E1 and up-regulating the PPAR-alpha expression.

PMID- 25371575
TI  - Ethnomedicines of highly utilized plants in the temperate Himalayan region.
AB  - BACKGROUND: Himalayan region of Pakistan has been known as a rich source for
      valuable medicinal plants. The present work is the documentation of indigenous
      knowledge of highly utilized plants as natural remedy by the local inhabitants of
      the northwest part of the country. METHODOLOGY: Data on highly utilized medicinal
      plants were collected during May-September 2012 using semi-structured
      questionnaire from the elders, local herbalists and medicinal plants collectors.
      RESULTS: In total about 53, plants belonging to 38, families were highly utilized
      in the study area, of which majority of those (43), were medicinal plants. The
      most frequent part used in preparation of different medicinal remedies is leaves
      (53%). Most of the medicinal plant species (14) were used as antipyretic. The
      inhabitants of the study area were producing ethno-medicines mostly in crushed
      form (26%). Most of the remedies (74%), were taken orally within the study area.
      Ten species were found most valuable from the local's perspective such as
      Bergenia ciliata, Hedera nepalensis and Viola canescens. CONCLUSION: In
      conclusion, traditional healers depend largely on naturally growing medicinal
      plant species, which are under severe threat. This study can provide a basis for
      further phyto-chemical and pharmacological studies on the region's medicinal
      plants. Moreover, documentation of indigenous recipes would serve as preservation
      of the knowledge for the generations to come.

PMID- 25371574
TI  - Antibacterial and anti-biofilm activity of flavonoids and triterpenes isolated
      from the extracts of Ficus sansibarica Warb. subsp. sansibarica (Moraceae)
      extracts.
AB  - BACKGROUND: Ficus species are used in African traditional medicine in the
      treatment of a wide variety of ailments and diseases such as convulsive disorder,
      wound healing, gonorrhea, tuberculosis, diabetes, diarrhoeal infections,
      dysentery, malaria and HIV. The aim of this study was to isolate the
      phytochemical constituents in the plant and test them for their antibacterial
      activity. MATERIALS AND METHODS: The fruits, leaves and stem bark were extracted
      with organic solvents and the compounds in the extracts separated and purified by
      column chromatography before being identified by NMR spectroscopy and by
      comparison of the NMR data against values reported in the literature. The
      antibacterial activity of the pure compounds and extracts were tested using the
      disk diffusion method. RESULTS: Three triterpenes and three flavonoids: lupeol
      acetate (1); cycloart-23-ene-3,25-diol (2); beta-sitosterol (3); 5,7,4'
      trihydroxyflavan-3-ol (4); epicatechin (5); and isovitexin (6) were isolated in
      this study. Antimicrobial activity was observed at 8 mg mL(-1) for Staphylococcus
      aureus ATCC 29213 with four of the six isolated compounds, with no activity being
      observed at 1 - 4 mg mL(-1) against Escherichia coli ATCC 25922, E. coli ATCC
      35218 and S. aureus ATCC 43300. Epicatechin (5) was found to decrease adhesion of
      E. coli ATCC 25922 and S. aureus ATCC 29213. Decreased adhesion of S. aureus ATCC
      29213 was also observed with 5,7,4'-trihydroxyflavan-3-ol (4) and isovitexin (6).
      CONCLUSIONS: The results of this study provide baseline information on F.
      sansibarica's potential validity in the treatment of infections associated with
      Gram-positive microorganisms.

PMID- 25371576
TI  - The bioload and aflatoxin content of herbal medicines from selected states in
      Nigeria.
AB  - BACKGROUND: There is increased reliance on traditional herbal medicines by
      several millions of people worldwide, especially in West Africa and Nigeria in
      particular. This is due to escalating cost of good quality drugs and consequent
      proliferation of faked cheaper drugs. However, non standardization of production
      and handling methods have resulted in herbal medicines with varying quality and
      safety indices, thus resulting in possible public health concerns. This work
      investigated the microbial load and aflatoxin levels in herbal medicines from
      selected states in Nigeria. MATERIALS AND METHODS: A total of 210 samples
      obtained from various renowned herbal medicine practitioners from some selected
      states in Nigeria, based on their medicinal uses, were analyzed to determine the
      microbial load by the plate count method and aflatoxin contamination levels using
      thin layer chromatography with aflatoxin standards. RESULTS: At least six
      bacterial genera (Bacillus, Pseudomonas, Salmonella, EPEC, EHEC, Streptococcus
      and other coliforms) and 6 fungal genera (Aspergillus, Penicillium, Rhizopus,
      Cladosporium, Geotricum and Candida) were isolated. Aflatoxin B1, B2 and G1 were
      detected in varying concentrations in the samples analyzed, with an average
      occurrence of 18.6%. Some of these herbal concoctions were found to contain
      unacceptably high bioload, according to WHO standards. CONCLUSION: Microbial
      contamination and the presence of aflatoxins in herbal medicines appear to be an
      endemic problem in Nigeria, as observed in this work, probably due to poor
      observation of basic hygiene during preparations and poor storage conditions. The
      findings in this work may serve in developing and instituting public health
      standards for the production and safety of herbal remedies in Nigeria.

PMID- 25371578
TI  - Investigation of the effects of connective tissue mobilisation on quality of life
      and emotional status in healthy subjects.
AB  - BACKGROUND: Connective Tissue Massage (CTM) or Manipulation is a bodywork
      technique which lies at the interface between alternative approaches. The
      autonomic balancing responses to CTM can be useful in the treatment of anxiety.
      AIM: This study was planned to investigate the effects of connective tissue
      mobilization (CTM) on quality of life and emotional status in healthy subjects.
      Design; Prospective trial, Setting; Treatment and Population. The study was
      conducted on 100 volunteers (students). Students in second class were in CTM
      group (20,49+/-1,37 years) and students (19,50+/-1,15 years) educating in class 1
      were in control group. METHODS: Participants were assessed before and after CTM
      according to flexibility of trunk flexion, hamstring muscles, trunk
      hyperextension and lateral flexion. It was used The SF-36 Health-Related Quality
      of Life Inventory (SF-36) to assess general health status and Beck Depression
      Scale was used for assessing emotional status. RESULTS: It was observed a
      significant increase at lateral flexion to the right of trunk (p=0,03) in CTM
      group after application. It was found a significant difference (p=0,009) in
      emotional status between groups. It was found differences at general health level
      (p=0,001), limitations in emotional role (p=0,016) in SF-36. It was some
      differences in depression status and some subscales of SF-36 (general health,
      social status, emotional well-being, pain and energy levels) in favour of control
      group before application. It was no difference between groups after application.
      CONCLUSION: CTM could be used for minimizing depressive symptoms, improving
      quality of life in healthy young subjects.

PMID- 25371577
TI  - Antifungal and antihepatotoxic effects of sepia ink extract against oxidative
      stress as a risk factor of invasive pulmonary aspergillosis in neutropenic mice.
AB  - BACKGROUND: There is a great need for novel strategies to overcome the high
      mortality associated with invasive pulmonary aspergillosis (IPA) in
      immunocompromised patients. To evaluate the antifungal and antihepatotoxic
      potentials of Sepia ink extract, its effect on liver oxidative stress levels was
      analyzed against IPA in neutropenic mice using amphotercin B as a reference drug.
      MATERIALS AND METHODS: Eighty neutropenic infected mice were randomly assigned
      into four main groups. The 1(st) group was treated with saline, neutropenic
      infected (NI), the 2(nd) group was treated with ink extract (200 mg/kg) (IE) and
      the 3(rd) group was treated with amphotericin B (150 mg/kg) (AMB) and 4(th) group
      was treated with IE plus AMB. Treatment was started at 24 h after fungal
      inoculation (1*10(9) conidia/ml). RESULTS: The present study revealed good in
      vitro and in vivo antifungal activity of IE against A. fumigatus. IE
      significantly reduced hepatic fungal burden and returns liver function and
      histology to normal levels. Compared with the untreated infected group, mice in
      the IE, AMB, and IE+ AMB groups had increased glutathione reduced (GSH) and
      superoxide dismutase (SOD) and significantly reduced malondialdehyde (MDA) levels
      at 24 and 72 h after inoculation with A. fumigatus conidia. CONCLUSION: It is
      then concluded that in combination with antifungal therapy (AMB), IE treatment
      can reduce hepatic fungal burden, alleviate hepatic granulomatous lesions and
      oxidative stress associated with IPA in neutropenic mice.

PMID- 25371579
TI  - The immunostimulatory and antimicrobial property of two herbal decoctions used in
      the management of HIV/AIDS in Ghana.
AB  - BACKGROUND: HIV/AIDS is a pandemic retarding economic growth and destroying human
      capital globally. This study therefore investigated the perceived efficacy of
      Betula alba (BA) and Sutherlandia frutescens (SF) decoctions used in the
      management of HIV/AIDS in Ghana. MATERIALS AND METHODS: A study on the records of
      HIV/AIDS patients attending Habibi Herbal Clinic, Kumasi, Ghana, was conducted to
      obtain information on the initial viral load presented during their maiden visit
      and results after treatment with the herbal decoctions. The decoctions were
      assessed for immunostimulatory property in cyclophosphamide-induced
      immunosuppressed ICR mice. Total white blood cell count, as well as lymphocyte
      and neutrophil counts were determined and their effects compared with Levamisole.
      The decoctions were also screened for antimicrobial activity by the micro
      dilution method. RESULTS: The two herbal decoctions used significantly reduced (P
      <= 0.001) the patients' viral loads (47.42 +/- 17.28 % to 13.69 +/- 12.42 %;
      n=16). BA (1, 2, and 4 mg/kg) and SF (0.4, 0.8, and 1.6 mg/kg) caused significant
      increment (P <= 0.001) in total WBC and lymphocyte count in mice comparable to
      that produced by 2.5 mg/kg Levamisole. The decoctions also exhibited
      antimicrobial activity against gram negative and gram positive bacteria as well
      as Candida albicans (MIC 0.607 to 3.062 mg/ml). Phytochemicals present in both
      plants include saponins, terpenoids and coumarins. CONCLUSION: The Betula alba
      and Sutherlandia frutescens decoctions have interesting immunostimulatory and
      antimicrobial properties and hence could be useful in the management of HIV/AIDS
      and associated opportunistic infections.

PMID- 25371580
TI  - Antinociceptive, anti-inflammatory and antipyretic activities of the leaf
      methanol extract of Ruta graveolens L. (Rutaceae) in mice and rats.
AB  - BACKGROUND: Ruta graveolens has been used to treat toothache, earache, rheumatism
      and fever with little scientific evidence corroborating these uses. MATERIALS AND
      METHODS: The leaf methanol extract of Ruta graveolens was evaluated for
      antinociceptive activity using the acetic acid writhing and hot-plate tests in
      mice, also anti-inflammatory and antipyretic activities using the carrageenan
      induced oedema and E. coli-induced pyrexia tests in rats, respectively. RESULTS:
      R. graveolens (100 mg/kg, i.p.), significantly reduced the number of acetic acid
      induced writhes by 54 %. R. graveolens (400 mg/kg, i.p.), significantly delayed
      the reaction time in mice to thermal stimulation 15, 30, 45, and 60 min after
      treatment. Combined treatment of the lowest and sub-effective doses of the leaf
      methanol extract (25 mg/kg, i.p.), and indomethacin (10 mg/kg, i.p.)
      significantly reduced the number of acetic acid-induced writhes in mice. The leaf
      methanol extract of R. graveolens (50 - 400 mg/kg, i.p.), significantly reduced
      carrageenan-induced oedema over the 4 h period of testing. Combined treatment of
      the lowest doses of R. graveolens (25 mg/kg, i.p.) and indomethacin (2 mg/kg,
      i.p.) produced a significant reduction in carrageenan-induced oedema over the 4 h
      period of testing. R. graveolens (100 -400 mg/kg, i.p.) significantly reduced E.
      coli-induced pyrexia over the 5 h period of testing. Given together, the lowest
      dose of R. graveolens (25 mg/kg, i.p.) and pentoxifylline (10 mg/kg, i.p.)
      produced a significant reduction in pyrexia induced by E. coli (50 ug/kg, i.m.)
      over the 5 h period of measurement. The LD50 value obtained for R. graveolens was
      greater than 4000mg/kg (p.o), suggesting that the plant species may be safe in or
      nontoxic to mice. CONCLUSION: The data obtained indicate that R. graveolens has
      antinociceptive, anti-inflammatory and antipyretic activities, justifying the use
      of the plant species by traditional medicine practitioners in the management and
      treatment of pain, inflammation and fever.

PMID- 25371581
TI  - Evaluation of antibacterial activity of Prosopis juliflora (SW.) DC. leaves.
AB  - BACKGROUND: The ethnobotanical importance of Prosopis juliflora is well-known in
      the folkloric system of medicine for the treatment of various ailments. Although,
      the study related to the antibacterial potential of this plant, from Central
      India is scanty. MATERIAL AND METHODS: The in vitro antibacterial activity of
      Prosopis juliflora leaves collected from the local area was evaluated against ten
      bacterial type cultures by agar well diffusion assay. The crude extracts prepared
      by two methods separately with three different solvents were examined for the
      preliminary antibacterial activity and phytochemical screening, the results of
      which were used for the choice of solvent and mass extraction of crude extract.
      Solvent fractionation of crude extract was done employing two sets of solvents
      namely Set-PCE and Set-HDB which resulted in total, six organic and two aqueous
      fractions, which were finally subjected to antibacterial activities. RESULTS:
      Varying degrees of growth inhibition was shown by all the fractions against
      tested microorganisms. The highest antibacterial activity was observed in aqueous
      fractions as compared to solvent fractions. CONCLUSION: Isolation and
      characterization of the bioactive components can be further done by systematic
      screening of the most active solvent fraction which could lead to the possible
      source of new antibacterial agents.

PMID- 25371582
TI  - Preliminary study of plants used in ethnoveterinary medicine in Tunisia and in
      Italy.
AB  - BACKGROUND: A survey relative to the use of plants for the cure of animals in
      Tunisia was conducted in order to make a comparison with the same species (or
      similar ones) in central and southern Italy. MATERIALS AND METHODS: available
      bibliographical data both for Italy and for Tunisia were consulted. RESULTS:
      Thirty-nine plants, representing 22 families, used in Tunisia in ethnoveterinary
      medicine were reported, and comparisons made with close species used in Central
      and Southern Italy. Seven of the 39 species (about the 18% of the total) are not
      present in Italian flora. Fourteen of the 39 species (35% of the total) are also
      used in Italy. Camelidae (dromedaries and camels) are the most valuable types of
      domestic animals cured in Tunisia, but ovines, horses, bulls, dogs are also
      treated. Some uses coincide with those existing in different Italian regions. The
      plants used are the most common and most easily found in these areas. CONCLUSION:
      The present study confirms the convergence in ethnoveterinary medicine between
      Tunisia and Italy, even if it appears less significant than in human ethnobotany.
      Further studies are required in areas of Tunisia that have not yet been studied,
      in order to get the possibility of an evaluation of active compounds.

PMID- 25371583
TI  - Phytochemical investigation and anti-microbial activity of Clausena anisata
      (Willd), Hook.
AB  - BACKGROUND: Clausena anisata belongs to the family Rutaceae, a shrub widely used
      in West Africa for the treatment of bacterial and fungal infections of the skin
      including boils, ringworm and eczema. The study was designed to evaluate the
      antimicrobial activity and phytochemical screening of ethanol leaf extract of C.
      anisata (CLE). METHOD: Antimicrobial activity of CLE was investigated using agar
      well diffusion and micro-dilution methods against four Gram-positive bacteria
      (Bacillus substilis NCTC 10073, Staphylococcus aureus ATCC 25923, Enterococcus
      faecalis ATCC 29212, Bacillus thuringiensis ATCC 13838) and two Gram-negative
      bacteria (Pseudomonas aeruginosa ATCC 4853, Proteus vulgaris ATCC 4175) and a
      clinical isolate of Candida albicans. RESULTS: CLE was active against all test
      organisms with minimum inhibitory concentration (MIC), range of 0.5 to 7.0 mg/mL
      against Gram-positive bacteria, 2.5 to 1.0 mg/mL against Gram-negative bacteria
      and 5.5mg/mL against C. albicans. The MICs of the methanol fraction of CLE were
      0.6 mg to 5.0/mL and 1.0 to 3.0 mg/mL for Gram-positive and Gram-negative
      bacteria respectively. Chloroform fraction had MIC of 3.0 to 7.5 mg/mL and 2.0 to
      6.5 mg/mL for Gram-positive and Gram-negative bacteria, respectively and
      petroleum ether fraction had 4.5 to 8.0 mg/mL for Gram-positive and Gram-negative
      bacteria. The CLE exhibited static action against all test organisms within a
      range of 0.5 to 22.0 mg/mL. Phytochemical screening of C. anisata revealed the
      presence of tannins, flavonoids, steroids, saponins, glycosides and alkaloids.
      HPLC finger-printing of the CLE and its fractions were determined. CONCLUSION:
      These results may justify the medicinal uses of C. anisata for the treatment of
      microbial infections.

PMID- 25371584
TI  - Estimating the yin-yang nature of Western herbs: a potential tool based on
      antioxidation-oxidation theory.
AB  - BACKGROUND: One of the biggest obstacles to progress in traditional Chinese
      medicine (TCM) development in Western countries is the difficulty of applying the
      traditional concepts to the Western medicinal plants, which are not traditionally
      described in ancient literature. During recent years, new advances in the field
      of understanding Yin/Yang aspects from a modern bioscientific point of view have
      led to the conclusion that antioxidationoxidation concepts might mirror a Yin
      Yang relationship. METHODS: This study was intended to integrate the Yin-Yang
      theory of the traditional Chinese medicine with modern antioxidation-oxidation
      theory, and to propose a biochemical tool based on redox parameters (e.g.
      antioxidant capacity, chemiluminescence-CL signal inducing capacity), usable for
      the classification of Western medicinal plants from Yin/Yang perspective. Trolox
      equivalent antioxidant capacity (TEAC) of six vegetal aqueous extracts (Symphitum
      officinalae (radix)-SYM, Inula helenium (radix)-INU, Calendula officinalis
      (flores)-CAL, Angelica arhanghelica (folium)ANG(F), Angelica arhanghelica (radix)
      ANG(R), Ecbalium Elaterium (fruits)-ECB) and luminol-enhanced chemiluminescence
      of PMNL on addition of these vegetal extracts were measured. Percentages from the
      maximal or minimal values obtained were calculated for each extract (TEAC%, PMNL
      stimulation%, PMNL inhibition%, relative speed of action% (RSA%%)), specific Yin
      Yang significance was assigned to each relative parameter. In the end, an
      integration of all the relative values was done, in order to find a global "Yin"
      or a "Yang" trait of each vegetal extract. RESULTS: TEAC decreased in the
      following order: SYM > INU > CAL >ANG(F) > ANG(R > ECB. Three vegetal extracts
      (SYM > INU > ECB) decreased the luminol-enhanced chemiluminescence of PMNL, two
      (ANG(R) > ANG(F)) increased it, while one (CAL) had a dual effect. After the
      integration of the percentages, CAL was found to have a global "Yang" trait,
      while the rest of the plants had a global "Yin" trait. CONCLUSIONS: TEAC% and
      PMNL inhibition% appears to correlate with the Yin properties of herbs, while
      PMNL stimulation% and RSA% might correlate with Yang aspects within the formal
      TCM classification system, and may be useful criteria in describing the Western
      herbs from a TCM point of view.

PMID- 25371585
TI  - Comparitive study on volatile aroma compounds of two different garlic types
      (Kastamonu and Chinese) using gas chromatography mass spectrometry (HS-GC/MS)
      technique.
AB  - BACKROUND: The medicinal use of garlic is much older than its usage as a food.
      The medical importance of garlic comes forward for its sulfur-containing
      components. In this study, it was aimed to compare Kastamonu garlic type with
      Chinese garlic type based on their aroma profiles. MATERIALS AND METHODS: Fresh
      Kastamonu garlic samples harvested from Kastamonu region of Turkey and Chinese
      garlic samples obtained from Turkish market were used as plant material. Volatile
      aroma compounds were determined using Headspace Gas Chromatography Mass
      Spectrometry (HS-GC/MS). RESULTS: Sixteen and twenty aroma components were
      identified in Kastamonu and Chinese garlic types, respectively. Kastamonu garlic
      type was found to be richer than Chinese garlic types in terms of sulfur
      containing compounds. Diallyl disulphide, which is one of these components, was
      detected at level of 41.87% and 34.95% in the Kastamonu and Chinese garlic types,
      respectively. Also di-2-propenyl trisulfide was found only in Kastamonu garlic
      types. Disulfide, methyl 2-propenyl was determined at similar levels in both
      garlic types. CONCLUSION: The majority of garlic grown in Kastamonu region of
      Turkey is assessed by medical companies. CONCLUSION: The results of the current
      study showed that Kastamonu garlic type has important medical properties.
      Therefore, this garlic can also be used in the medical field, as well as the
      consumption as food.

PMID- 25371586
TI  - Evaluation of the antioxidant activity of root extract of pepper fruit (Dennetia
      tripetala), and it's potential for the inhibition of lipid peroxidation.
AB  - BACKGROUND: The antioxidant properties of ethanolic root extract of pepper fruit
      (Donnetia tripetala), and its effect on lipid peroxidation of some fresh beef
      tissues during frozen storage were investigated. MATERIALS AND METHODS: The
      antioxidant parameters were assessed using standard methods, while
      malondialdehyde levels of different fresh beef tissue sections treated with the
      extract prior to freezing, were estimated in a colorimetric reaction with
      thiobarbituric acid. RESULTS: The H2O2-scavenging ability of the extract was
      similar to that of ascorbic acid, with a maximum scavenging power of 55.61 +/
      4.98%, and an IC50 value of 86ug/ml. The extract exhibited a concentration
      dependent ferric ion-reducing power, although this was significantly lower
      relative to that of the ascorbic acid (p < 0.05). The total phenolic content was
      212.5 +/- 0.002 mg/g, while the nitric oxide-scavenging ability was 64.33 +/-
      0.2% after 150 min. The capacity of the extract to inhibit lipid peroxidation in
      frozen heart muscle slices was significantly higher than that of vitamin C (p < 0
      .05), but comparable to vitamins C and E in frozen testes and kidney slices.
      CONCLUSION: These results suggest that the root extract of D. tripetala is rich
      in antioxidants which can be applied to meat preservation during refrigerated
      storage.

PMID- 25371587
TI  - Evaluation of the antinociceptive effect of the ethanolic extract of Punica
      granatum.
AB  - BACKGROUND: There are severe adverse effects of analgesic drugs on human body.
      Extraction of analgesic drugs from natural products has therefore become the
      prime objective of the study. In this study, we aimed to evaluate the
      antinociceptive activity of the pomegranate fruit. MATERIALS AND METHODS:
      Antinociceptive activity of ethanol pomegranate extract was examined using three
      models of pain: the writhing test, the hot tail flick test and the plantar test.
      The ethanolic extract of pomegranate was administered by oral gavages in doses of
      (100,150 and 200mg/kg, p.o (orally)), for all the tests and compared with aspirin
      (100mg/kg, p.o.) which was considered as the standard drug. Phytochemical
      screening and HPLC analysis of the plant species was carried out. RESULTS: In the
      writhing test, the index of pain inhibition (IPI) was 37% for ethanolic extract
      of pomegranate (200mg/kg, p.o.), and 59% for aspirin. In the hot tail flick test,
      the ethanolic extract of pomegranate (200mg/kg, p.o.), has shown significant
      analgesia reaching its peak at 60 min maximum possible analgesia (MPA), was 24.1%
      as compared with aspirin 37.5%. Hyperalgesia was successfully induced by the
      plantar test and the ethanol extract of pomegranate (100,150,200mg/kg, p.o.),
      reduced the hyperalgesia in a dose dependent manner comparable to aspirin at
      (100mg/kg, p.o.). HPLC analysis revealed the presence of gallic acid, ellagic
      acid and Punicalagins A&B. CONCLUSION: The results demonstrated that ethanol
      pomegranate extract has an antinociceptive effect that may be related to the
      presence of identified phytochemicals.

PMID- 25371588
TI  - Virulence genotype and phylogenetic groups in relation to Chinese herb resistance
      among Escherichia coli from patients with acute pyelonephritis.
AB  - BACKGROUND: Clinical isolates of herb-resistant uropathogenic E. coli were
      isolated. It was possible that the virulence genotypes and phylogenetic
      background of E. coli differed between Chinese herb-resistant E. coli and 
      susceptible isolates. For this purpose, the prevalence of virulence factors (VFs)
      and phylogenetic background, with regard to Chinese herb resistance, among E.
      coli strains causing acute pyelonephritis from China were investigated. MATERIALS
      AND METHODS: E. coli isolates from patients with acute pyelonephritis were used
      in this study. Standard disc diffusion methodology was used to test the
      susceptibility of Chinese herbal concoction against E. coli strains. Multiplex
      PCR amplifications employed three markers (chuA, yjaA, and TSPE4.C2) to classify
      E. coli isolates into one of four phylogenetic groups (group A, B1, B2, or D).
      The isolates were also tested for 14 virulence-associated traits (VFs) of
      uropathogenic E. coli. RESULTS: A total of 115 E. coli strains were isolated. 79
      (68.7%) were susceptible and 36 (31.3%) were resistant to the herbal concoction.
      20.9% of the isolates encoded three or more of VFs for which they were screened,
      with 13.9% in susceptible isolates and 36.1% in resistant isolates. The key VFs
      (fyuA and/or iutA siderophores) present in >80% of isolates. The papA and papC
      adhesins were detected in the majority of resistant isolates (72.2% and 63.9%
      respectively). 78.5% of susceptible isolates belong to phylogenetic groups A,
      while 83.3% of resistant isolates belong to group B2. CONCLUSION: PapA and papC
      are significant VFs with an essential role in contributing to Chinese herb
      resistance. Chinese herb-resistance is associated with a shift towards more
      virulent strains and B2 phylogenetic group.

PMID- 25371589
TI  - Indigenous traditional knowledge and usage of folk bio-medicines among Rongmei
      tribe of Tamenglong district of Manipur, India.
AB  - BACKGROUND: Rongmei tribe (Kooki), are inhabitant of the Charoi Chagotlong
      village, Tupul, Tamenglong district of Manipur have the traditional knowledge of
      folk bio-medicine based on diverse plant species for the prevention and cure of
      certain chronic diseases. The aim of this study was to document and preserve the
      indigenous knowledge of the Rongmei tribe on folk medicines. MATERIAL AND
      METHODS: The present work was based on methodical field survey conducted between
      2010, to 2013. Local people of within 30-70 age groups of both sexes were
      interviewed and a group discussion (using a structured interview schedule), was
      held to know about the type of plant parts used in folk bio-medicines, and their
      mode of use. The interviewers were drawn from a wide array of disciplines
      (Vendors, Farmers club, NGO's, scientific societies, etc.), to obtain maximum
      information in relation to folk bio-medicine. RESULTS: A total of 60 species
      belonging to 36 different families (ranging from gymnosperm to angiosperm with
      medicinal benefits), were discussed briefly with significant emphasis on their
      local name, scientific name, family, parts used; they claimed to cure various
      ailments from these plants in this mode of folk bio-medicine. The different plant
      parts used were leaves, fruits, bulbs, bark, roots, seeds, tuber, trunk, flower,
      shoot, whole plant, rhizome, stem, wood and berries. Based on a life form of the
      reported plants comprise herbs, shrubs, trees, grasses, bulb, vine, climber,
      tuber and succulent. CONCLUSION: Efforts should be made to promote the use of
      traditional biomedicines within rural communities to preserve the traditional
      knowledge.

PMID- 25371590
TI  - Dietary supplements in the management of hypertension and diabetes - a review.
AB  - BACKGROUND: The use of alternative therapies like herbs and dietary supplements
      is very common among hypertensive and diabetic patients all over the globe.
      Hypertension is a silent disease that causes increase in cardiovascular,
      cerebrovascular, renal morbidity and mortality whereas diabetic complications
      cause heart attack, stroke, blindness and kidney disease. These are serious and
      chronic metabolic disorders that have a significant impact on the health, quality
      of life, and life expectancy of patients, as well as on the health care systems.
      Orthodox drugs used for the treatment of hypertension and diabetes produce side
      effects such as headache, nausea, vomiting, stomach pain, constipation, diarrhea,
      weakness, fatigue and erectile dysfunction. The need for considering alternate
      therapies in the form of dietary supplements known to promote good health, having
      little or no side effects therefore arises. MATERIALS AND METHODS: This review
      was carried out using comprehensive and systematic literature reports on the
      concurrent use of dietary supplements in the management of diabetes and
      hypertension. Empirical searches were conducted using Google scholar
      (http://scholar.google.com), and Science Direct (http://www.sciencedirect.com).
      In addition to these databases, the University database was also used. Searches
      were also undertaken using keyword combinations such as dietary supplements and
      the names of the diseases in question. RESULT AND DISCUSSION: This review
      chronicled the therapeutic values of vitamins, minerals, amino acids, fruits,
      vegetables, herbs and other botanicals used as dietary supplements. Results show
      that these supplements provided better and safe substitutes to toxic and
      expensive conventional drugs. Generally dietary supplements are free from major
      side effects, readily available and affordable. It is envisaged that the use of
      dietary supplement will promote good health and improve the status of
      hypertensive and diabetic patients. CONCLUSION: Medical doctors are therefore
      encouraged to incorporate dietary supplements into the regimen employed for
      hypertension and diabetes management.

PMID- 25371591
TI  - Anti-inflammatory and antioxidant activities of methanol extracts and alkaloid
      fractions of four Mexican medicinal plants of Solanaceae.
AB  - BACKGROUND: Methanol extracts and alkaloid fractions of different parts of four
      plant species belonging to Solanaceae family and used in Mexican traditional
      medicine were investigated for their total phenolic contents, anti-inflammatory
      and antioxidant properties. MATERIALS AND METHODS: The total phenolic compounds
      of each extract was determined according to the Folin-Ciocalteu method, while the
      in vitro radical scavenging activities of the extracts were assessed using the
      DPPH and ABTS radicals. The in vivo anti-inflammatory activity was determined
      using the TPA-induced mouse ear edema model. RESULTS: The methanol extracts
      contained the highest concentrations of phenolic compounds and also exhibited the
      best reducing power on the DPPH and ABTS radicals, in a concentration-dependent
      fashion. However, the anti-inflammatory activity did not follow the same trend,
      as some alkaloid fractions that showed low radical reducing power exhibited the
      strongest anti-inflammatory activity. CONCLUSION: The methanol extract obtained
      from the flowers of Nicotiana glauca presented the best overall performance with
      the largest amount of phenolic compounds (111 ug garlic acid equivalents/g of
      extract), the best antioxidant activity (94.80% inhibition of DPPH and 97.57% of
      ABTS) and the highest anti-inflammatory activity (81.93% inhibition of the
      inflammation).

PMID- 25371592
TI  - Comparative anti-inflammatory and hepatoprotective activities of Astragalus
      gummifer Labill herb and roots in rats.
AB  - BACKGROUND: The Astragalus gummifer (F. Fabaceae), herb and roots were studied
      for anti-inflammatory and hepatoprotective activities. MATERIALS AND METHOD: The
      alcoholic extracts of Astragalus gummifer (F. Fabaceae), herb (AGHE), and roots
      (AGRE), were used for anti-inflammatory and hepatoprotective activities in Wister
      rats. The effects of AGHE and AGRE were compared with the standard drugs
      Phenylbutazone and silymarin, for anti-inflammatory and hepatoprotective
      activities respectively. RESULT: Both extracts showed significant anti
      inflammatory activity (P< 0.001). AGRE showed comparatively more significant
      hepatoprotective activity (P< 0.001), than AGHE (P< 0.05); at doses of 250 and
      500 mg/kg body weight as manifested by lowering the serum levels of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl
      transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin. The
      hepatoprotective activity was, also, supported by total protein (TP),
      malondialdehyde (MDA), nonprotein sulfhydryls (NP-SH), and histo-pathological
      studies of liver tissue. DISCUSSION: To the best of our knowledge, this is the
      first report of the anti-inflammatory and hepatoprotective activities of
      Astragalus gummifer. The results of present studies indicated that both AGHE and
      AGRE can be used in inflammatory conditions, while investigation supports the use
      of AGRE in cases that hepatoprotection are required in the hepatotoxic
      conditions. More supportive studies are required before clinical recommendation.

PMID- 25371593
TI  - The preliminary assessment of anti-microbial activity of HPLC separated
      components of Kirkia wilmsii.
AB  - BACKGROUND: Most communities in developing countries rely on traditional
      medicines for the treatment of diseases. In South Africa, the Limpopo province,
      within the Lebowakgomo district, uses tuberous roots of Kirkia wilmsii, after
      infusion in water for the treatment of a wide range of diseases by Sotho
      communities. MATERIALS AND METHODS: The main objective of the study was to assess
      the anti-microbial activity of separated aqueous components of the Kirkia wilmsii
      tuberous roots. The clear aqueous extracts that were obtained after a 0.45 um
      membrane filtration (Millipore Millex-HV Hydrophillic PVDF filter), were then
      injected into a preparative high performance liquid chromatography instrument in
      which pure components, as shown by peaks, were collected and evaluated for anti
      microbial activity against a range of microorganisms. RESULTS: The eight
      separated components were obtained, out of which four components showed anti
      microbial activity (AMA). The freeze dried components were re-dissolved in
      deionised water and then evaluated for AMA against Vibrio cholerae, Shigella
      dysenteriae, Aeromonas hydrophilia, Salmonella typhi Proteus mirabilis,
      Escherichia coli, Staphylococcus aureus, Candida albicans and Enterobacter
      aerogenes. Component one exhibited antimicrobial activity against Shigella
      dysenteriae, Aeromonas hydrophilia, Salmonella typhi, Proteus mirabilis,
      Escherichia coli and Staphylococcus aureus with a minimum inhibitory
      concentration (MIC), of 3.445 mg/ml. Component five was only active against
      Proteus mirabilis with a MIC of 0.08 mg/ml. Component 7, was active against
      Shigella dysenteriae, Staphylococcus aureus and Escherichia coli with a MIC of
      0.365 mg/ml against both Shigella dysenteriae and Staphylococcus aureus and 0.091
      mg/ml against Escherichia coli. Component 8, was active against Shigella,
      Aeromonas hydrophilia, Salmonella, Proteus mirabilis, Escherichia coli with a MIC
      of 155 mg/ml. CONCLUSION: Only four out of eight aqueous extracts showed AMA
      against both gram negative and positive bacteria and showed no AMA against
      Candida albicans, Enterobacter aerogenes and Vibrio cholerae. Therefore the
      Kirkia wilmsii plant root may be used as a broad spectrum antibiotic.

PMID- 25371594
TI  - Inventory of medicinal flora from Thal Desert, Punjab, Pakistan.
AB  - BACKGROUND: This article reports the preliminary findings of an ethno-botanical
      survey that was carried out in the Thal Desert, Punjab, Pakistan during 2010 to
      2013. The aim of this study was to document the traditional use of medicinal
      plants from the study area. MATERIALS AND METHODS: The whole area was surveyed
      for inventorying medicinal flora by using a semi-structured questionnaire.
      RESULTS: The people of the study area are extremely knowledgeable, hence reported
      120 plants which are being used in treating various human diseases. The detailed
      inventory including botanical name, parts used, method of preparation and
      diseases treated is provided in this paper. CONCLUSION: This study revealed that
      the inhabitants possessed empirical knowledge of medicinal plants which would be
      useful in developing health care products and preserving traditional cultures as
      well as phyto-diversity.

PMID- 25371595
TI  - Bioactivity-guided isolation of anticancer agents from Bauhinia kockiana Korth.
AB  - BACKGROUND: Flowers of Bauhinia kockiana were investigated for their anticancer
      properties. METHODS: Gallic acid (1), and methyl gallate (2), were isolated via
      bioassay-directed isolation, and they exhibited anticancer properties towards
      several cancer cell lines, examined using MTT cell viability assay. Pyrogallol
      (3) was examined against the same cancer cell lines to deduce the bioactive
      functional group of the phenolic compounds. RESULTS: The results showed that the
      phenolic compounds could exhibit moderate to weak cytotoxicity towards certain
      cell lines (GI50 30 - 86 uM), but were inactive towards DU145 prostate cancer
      cell (GI50 > 100 uM). CONCLUSION: It was observed that pyrogallol moiety was one
      of the essential functional structures of the phenolic compounds in exhibiting
      anticancer activity. Also, the carboxyl group of compound 1 was also important in
      anticancer activity. Examination of the PC-3 cells treated with compound 1 using
      fluorescence microscopy showed that PC-3 cells were killed by apoptosis.

PMID- 25371598
TI  - Recent Decisions of the European Court of Justice of the European Union on
      Supplementary Protection Certificates: A Few Answers-Many Questions.

PMID- 25371596
TI  - Individually tailored screening of susceptibility to sarcopenia using p53 codon
      72 polymorphism, phenotypes, and conventional risk factors.
AB  - BACKGROUND AND AIM: p53 activity plays a role in muscle homeostasis and skeletal
      muscle differentiation; all pathways that lead to sarcopenia are related to p53
      activities. We investigate the allelic frequency of the TP53 codon 72 in exon 4
      polymorphism in the Italian female population and the association with
      appendicular skeletal muscle mass index in normal weight (NW), normal weight
      obese (NWO), and preobese-obese (Preob-Ob) subjects. METHODS: We evaluated
      anthropometry, body composition, and p53 polymorphism in 140 women distinguished
      in NW, NWO, and Preob-Ob. RESULTS: *Arg/*Arg genotype increases sarcopenia risk
      up to 20% (*Arg/*Arg genotype OR = 1.20; 95% CI = 0.48-2.9; *proallele carriers
      OR = 0.83; 95% CI = 0.83-2.06). The risk of being sarcopenic for *Arg/*Arg
      genotype in NWO and Preob-Ob is 31% higher than NW carriers of *proallele (RR =
      0,31, 95% CI = 0,15-0,66, P = 0,0079). We developed a model able to predict
      sarcopenia risk based on age, body fat, and p53 polymorphism. CONCLUSION: Our
      study evidences that genotyping TP53 polymorphism could be a useful new genetic
      approach, in association with body composition evaluations, to assess sarcopenia
      risk.

PMID- 25371597
TI  - Elevated plasma stromal-cell-derived factor-1 protein levels correlate with
      severity in patients with community-acquired pneumonia.
AB  - BACKGROUND: The aim of this study was to investigate differential changes in
      plasma levels of stromal-cell-derived factor-1 (SDF-1) before and after
      antibiotic treatment in patients with community-acquired pneumonia (CAP) and
      observe the association between the severity of CAP and the plasma SDF-1 level.
      METHODS: We gathered blood specimens from 61 adult CAP patients before and after
      antibiotic treatment and from 60 healthy controls to measure the plasma
      concentrations of SDF-1 by using an enzyme-linked immunosorbent assay. RESULTS:
      The plasma SDF-1 concentration was elevated significantly in patients with CAP
      before receiving treatment compared with the controls and decreased significantly
      after the patients received treatment. Leukocyte (WBC) and neutrophil counts and
      C-reactive protein (CRP) levels decreased significantly after antibiotic
      treatment. Moreover, differences in the plasma concentration of SDF-1 were
      significantly correlated with PSI, CURB-65, and APACHE II scores (r = 0.389, P =
      0.002, and n = 61; r = 0.449, P < 0.001, and n = 61; and r = 0.363, P = 0.004,
      and n = 61, resp.). CONCLUSIONS: An elevated plasma SDF-1 concentration can be
      used as a biological marker for the early diagnosis of CAP and for the early
      detection of its severity.

PMID- 25371599
TI  - A novel rose hip preparation with enhanced anti-inflammatory and
      chondroprotective effects.
AB  - Rose hip powder (RHP) alleviates osteoarthritis (OA) due to its anti-inflammatory
      and cartilage-protective properties. Substances contained in RHP might contribute
      to its clinical efficacy. The activity of two RHP (i.e., RH-A, from the whole
      fruit, RH-B, from fruits without seeds) was investigated in human peripheral
      blood leukocytes (PBL) and primary chondrocytes (NHAC-kn). RH-A and RH-B
      diminished the secretion of chemokines and cytokines in LPS/IFN-gamma-activated
      PBL, including CCL5/RANTES, CXCL10/IP-10, interleukin- (IL-) 6, and IL-12. Most
      effects were transcriptional, since gene expression levels were significantly
      influenced by RH-A and RH-B. In IL-1beta treated normal chondrocytes (NHAC-kn),
      both RH preparations reduced the expression of matrix metalloproteinase- (MMP-)
      1, MMP-3, and MMP-13 and ADAMTS-4. These changes are associated with diminished
      inflammatory damage or cartilage erosion. Principal component analysis revealed
      that (1) RH-A and RH-B modified a large pattern of biomarkers, and (2) RH-B
      outperformed RH-A. Furthermore, RH-B contained more chondroprotective and anti
      inflammatory constituents than RH-A. Thus, RHP contributed to restore cellular
      homeostasis in PBL and chondrocytes. RH preparations from fruits without seeds
      are thus expected to have an improved OA-preventive or OA-therapeutic profile, as
      subsequently shown in a related clinical trial. 

PMID- 25371600
TI  - Saudi oncology society and Saudi urology association combined clinical management
      guidelines for urothelial urinary bladder cancer.
AB  - In this report, updated guidelines for the evaluation, medical, and surgical
      management of transitional cell carcinoma of the urinary bladder are resented.
      They are categorized according the stage of the disease using the TNM staging
      system 7(th) edition. The recommendations are presented with supporting level of
      evidence. 

PMID- 25371602
TI  - Saudi oncology society and Saudi urology association combined clinical management
      guidelines for renal cell carcinoma.
AB  - In this report, updated guidelines for the evaluation, medical and surgical
      management of renal cell carcinoma are presented. They are categorized according
      the stage of the disease using the tumor node metastasis staging system 7(th)
      edition. The recommendations are presented with supporting evidence level. 

PMID- 25371601
TI  - Saudi oncology society and Saudi urology association combined clinical management
      guidelines for prostate cancer.
AB  - In this report, updated guidelines for the evaluation, medical, and surgical
      management of prostate cancer are presented. They are categorized according the
      stage of the disease using the tumor node metastasis staging system 7(th)
      edition. The recommendations are presented with supporting evidence level. 

PMID- 25371603
TI  - Saudi oncology society and Saudi urology association combined clinical management
      guidelines for testicular germ cell tumors.
AB  - In this report, updated guidelines for the evaluation, medical, and surgical
      management of germ cell tumor of testes are resented. They are categorized
      according the stage of the disease using the tumor-node-metastasis staging system
      7(th) edition. The recommendations are presented with supporting level of
      evidence. 

PMID- 25371604
TI  - Plasma rennin activity: Early indicator of renal injury in bilateral
      pelviureteric junction obstruction in children.
AB  - OBJECTIVE: The objective of the present study is to analyze the early indicators
      of renal injury in children with bilateral pelviuretric junction obstruction.
      MATERIALS AND METHODS: We investigated 23 children, 46 kidney units who were
      diagnosed with bilateral pelvi-ureteric junction obstruction (PUJO) and underwent
      unilateral or bilateral pyeloplasty between January 2001 and December 2011.
      Ipsilateral kidney biopsy was performed during pyeloplasty. Kidney biopsy results
      were divided into three categories. Pre-operative investigation included
      ultrasonography with the Society of Fetal Urology (SFU) grading, plasma rennin
      activity (PRA) and differential renal function (DRF). RESULTS: Out of 23 children
      there were 17 (73.9%) boys while 6 (26.1%) girls. Median age at operation was
      35.4 months (range: 9-60 months). Unilateral pyeloplasty was performed in 14
      (60.8%), simultaneous bilateral pyeloplasty in 2 (8.6%) and sequential bilateral
      pyeloplasty in 7 (30.4%). CONCLUSION: In bilateral PUJO where DRF and SFU grading
      of hydronephrosis did not correctly reflect renal injury, PRA showed a
      significant relationship with renal histopathologic grade and could be an early
      indicator of renal injury in bilateral PUJO.

PMID- 25371605
TI  - Cystatin C for early detection of acute kidney injury after laparoscopic partial
      nephrectomy.
AB  - INTRODUCTION AND OBJECTIVES: Mortality due to AKI has not changed significantly
      over the past 50 years. This is due in part to failure to detect early AKI and to
      initiate appropriate therapeutic measures. There is therefore a need to identify
      biomarkers that would improve the early detection of AKI. The objective of this
      study was to assess whether cystatin C levels obtained at specific timepoints
      during laparoscopic partial nephrectomy (PN) could be early predictors of AKI.
      MATERIALS AND METHODS: Twenty-five patients underwent laparoscopic PN for organ
      confined tumors. All procedures were performed by two surgeons in a single
      institution. Plasma samples were collected preoperatively, and post-unclamping at
      5, 20, 120 min and on the day following surgery. Plasma cystatin C was measured
      by enzyme-linked immunosorbent assay. Correlation between levels of cystatin C
      and other parameters of interest were assessed in order to define cystatin C
      ability to predict AKI and loss of renal function following laparoscopic PN.
      RESULTS: The mean baseline eGFR was 93 ml/min/1.73 m(2). Warm ischemia time
      varied between 16 and 44 min. Post-operative day 1 (POD1) cystatin C levels
      compared to baseline were increased in 13 (52%) of the patients. There was a high
      correlation between the difference of POD 1 and baseline value, and eGFR in the
      immediate postoperative period (r = -0.681; P = 0.0002) and at 12-month follow-up
      (r = -0.460, P = 0.048). However, the variation in cystatin C levels at earlier
      timepoints were not associated to AKI nor renal function. CONCLUSIONS: High
      increase in POD 1 cystatin C levels from baseline may help identify patients with
      AKI and those at higher risk of chronic kidney disease, following laparoscopic
      PN.

PMID- 25371606
TI  - Predictive factors for residual tumor and tumor upstaging on relook transurethral
      resection of bladder tumor in non-muscle invasive bladder cancer.
AB  - CONTEXT: Relook transurethral resection of bladder tumor (TURBT) improves the
      diagnostic and therapeutic efficacy of primary TURBT. However, it is still not
      established as to which category of patients would benefit most from this repeat
      invasive procedure. AIMS: This prospective interventional study was designed to
      identify the category of patients with non-muscle invasive bladder cancer who may
      benefit from a routine relook procedure. SETTING AND DESIGN: A total of 52
      consecutive patients with biopsy proven non muscle invasive bladder cancer on
      primary TURBT underwent a relook TURBT between March 2011 and September 2012.
      MATERIALS AND METHODS: The incidence of residual tumor and tumor upstaging on
      relook procedure was correlated with various histopathological (stage, grade,
      CIS, presence of muscle) and cystoscopic (type and focality of tumor, any
      apparent field change) parameters on primary TURBT. RESULTS: Out of the total 52
      patients, 23 (44.2%) had a residual tumor on relook TURBT. 12 (23.1%) were
      upstaged (of these 9 i.e. 17.3% to muscle invasion). While most of the parameters
      studied showed a positive correlation with incidence of residual tumor and
      upstaging to muscle invasion, statistical significance (for both) was reached
      only for tumor stage (P = 0.028 and 0.010), tumor grade (P = 0.010 and 0.002) and
      tumor type (solid vs. papillary; P = 0.007 and 0.001). Carcinoma in situ showed a
      significant correlation with incidence of residual tumor (P = 0.016) while the
      absence of muscle in the primary TURBT specimen was significantly associated with
      upstaging to muscle invasive disease (P = 0.018). STATISTICAL ANALYSIS: The data
      was analyzed using SPSS software v. 16.0. CONCLUSIONS: Relook TURBT may be
      especially recommended for high grade and T1 tumors and tumors with a
      solid/sessile appearance on primary TURBT especially when deep muscle was absent
      in the primary TURBT specimen.

PMID- 25371607
TI  - The comparison of ultrasound and non-contrast helical computerized tomography for
      children nephrolithiasis detection.
AB  - AIMS: Nephrolithiasis is less common in children than adults, but its diagnosis
      and management in children may be more perplexing. In this article, we compare
      two imaging ultrasound (US) and non-contrast helical computerized tomography (CT)
      for diagnosis of nephrolithiasis. SUBJECTS AND METHODS: A total of 20 children
      who diagnosed as nephrolithiasis by US were imaged simultaneously by non-contrast
      helical CT. Their history like as family history in first and second degree
      relatives and urine analysis for hematuria and urine randomly calcium to
      creatinine ratio was obtained. All data analyzed by chi(2) and Mann-Whitney U
      test in SPSS 16 and P < 0.05 was considered to be significant. RESULTS: Out of 20
      cases, only 5 cases diagnosed as nephrlithiasis by US were confirmed by CT method
      2 out of 20 cases had another extrarenal origin for their complaint who diagnosed
      wrongly as nephrolithiasis by US. Stone size based of US that was confirmed by CT
      method was larger 4.6 +/- 1.5 (minimum 3 max 6 mm) than non-confirmed ones 2.3 +/
      0.7 mm (P 0.002). Hematuria occurred more in correct diagnosed compared with
      misdiagnosed (P 0.005). Positive family history and urine calcium ratio was not
      differed between two groups. CONCLUSIONS: Non contrast helical CT is essential to
      confirm of nephrolithiasis and other extrarenal origin of complaints, which
      diagnosed wrongly as nephrolithiasis in children. Stone size and presence of
      hematuria are two major factors for right diagnosis of nephrolithiasis as US
      method but Urine calcium excretion ratio or positive family history cannot be
      predictive as this study.

PMID- 25371608
TI  - The effects of combined free radical scavenger and sildenafil therapy on age
      associated erectile dysfunction: An animal model.
AB  - INTRODUCTION: Aging results in erectile dysfunction that is partially attributed
      to decreased nitric oxide (NO) and increased free radical generation. Vitamin E
      enhances endothelial cell function and acts as a free radical scavenger; however,
      its benefits on erectile function in the elderly are unknown. AIMS: The aim of
      the following study is to determine if Vitamin E alone, or in combination with
      the phosphodiesterase 5 inhibitor sildenafil, may improve erectile function and
      the NO signaling in a cohort of aged (13-15 month old) rats. MATERIALS AND
      METHODS: Male Sprague-Dawley rats (n = 28) were divided based upon age into young
      (4-5 months old, n = 7) and aged (13-15 months old, n = 21) cohorts. Aged rats
      were treated with Vitamin E, sildenafil or a combination of both. Penile
      cavernosal and dorsal nerve tissues were evaluated for neuronal nitric oxide
      synthase (nNOS) and caveolin-1 expression. Erectile function was assessed through
      intra-cavernous pressure (ICP) recordings. RESULTS: nNOS and cavoelin-1 were
      significantly decreased in aged rats compared with young controls. In aged rats,
      both Vitamin E and sildenafil partially recovered nNOS expression but when
      combined, a synergistic elevation in nNOS was observed. The significant decreases
      in ICP recorded in aged rats were improved with sildenafil; however, Vitamin E
      did not yield any additional improvements in ICP. CONCLUSIONS: Diminished levels
      of nNOS and caveolin-1 are found in aged rats. When combined with sildenafil,
      Vitamin E synergistically increased nNOS expression. Since biochemical gains were
      not realized physiologically, other contributing factors likely exist.

PMID- 25371609
TI  - Relationship between development of urethral stricture after transurethral
      resection of prostate and glycemic control.
AB  - OBJECTIVES: The purpose of this study is to investigate the association of
      glycemic control prior to TUR-P and postoperative urethral stricture development.
      MATERIALS AND METHODS: Of the 168 patients with a diagnosis of urethral
      stricture, who underwent internal urethrotomy in our hospital were
      retrospectively analyzed for this study. 98 patients who underwent monopolar TUR
      P in our hospital previously and were developed urethral stricture were divided
      into two groups as diabetic and nondiabetic. Based on their HbA1c concentrations,
      diabetics were allocated to two groups with good (HbA1c <=6.5%) or poor (HbA1c >
      6,5%) glycemic control. Time to internal urethrotomy and the other operative
      parameters were compared among groups. RESULTS: Time to internal urethrotomy
      after TUR-P was significantly shorter in diabetic patients with poor glycemic
      control than Group 1 and Group 2 (P = 0,02, P = 0,012) but no significant
      difference was found between Group 1 and Group 2 (P = 0,368). There was no
      significant difference in the mean diagnosed and resected prostate wight among
      groups There was no significant difference in the mean resection time and the
      mean time to urethral catheter removal among groups. CONCLUSIONS: Especially in
      poor glycemic control patients, urethral stricture development was seen in the
      early period after TUR-P. For this reason, in the elective TUR-P scheduled poor
      glycemic controlled patients the operation should be done after glycemic control.

PMID- 25371610
TI  - Evaluation of healing at urethral anastomotic site by pericatheter retrograde
      urethrogram in patients with urethral stricture.
AB  - INTRODUCTION: Stricture urethra has been always a surgical challenge. Different
      opinions regarding time require healing at anastomotic site after urethroplasty,
      so various strategies are there regarding time for post-operative catheter
      removal. In this study, healing was assessed by pericatheter retrograde
      urethrogram (PUG) before the catheter removal. MATERIALS AND METHODS: Prospective
      study was conducted from January 2006 to December 2009. Twenty eight cases of
      short-segment urethral stricture (<2 cm) who underwent urethroplasty were
      included and divided into two groups depending upon etiology; post-traumatic
      group (road traffic accident/straddle type injury) and iatrogenic stricture group
      (due to prolong catheterization/after cystoscopy/Faulty Foleys balloon
      placement). Post-operative PUG was done on 14(th) post-operative day in all
      patients for healing assessment. Extravasation of dye on PUG was taken as
      anastomotic leak. If the patient had not showed extravasation, the catheter was
      removed. Otherwise it was kept further for next one week and again PUG was done
      for healing assessment. RESULTS: Extravasation of dye was noted in 4 patients
      (33%) of iatrogenic group and 14 patients (87.5%) of the post-traumatic group on
      14(th) post-operative day PUG. (P <= 0.05). The decision to remove catheter was
      depended upon PUG finding and it was safe, no complication was developed in any
      patient. CONCLUSION: Iatrogenic strictures have better healing than post
      traumatic stricture in the post-operative period. PUG is a safe and simple
      procedure and can guide about safe removal of catheter in the post-operative
      period.

PMID- 25371611
TI  - Evaluation of holmium laser versus cold knife in optical internal urethrotomy for
      the management of short segment urethral stricture.
AB  - OBJECTIVES: SACHSE COLD KNIFE IS CONVENTIONALLY USED FOR OPTICAL INTERNAL
      URETHROTOMY INTENDED TO MANAGE URETHRAL STRICTURES AND HO: YAG laser is an
      alternative to it. The aim of this study was to evaluate the role of urethral
      stricture treatment outcomes, efficacy, and complications using cold knife and
      Ho: YAG (Holmium laser) for optical internal urethrotomy. MATERIALS AND METHODS:
      In this prospective study included, 90 male patients age >18 years, with
      diagnosis of urethral stricture admitted for internal optical urethrotomy during
      April 2010 to March 2012. The patients were randomized into two groups containing
      45 patients each using computer generated random number. In group A (Holmium
      group), internal urethrotomy was done with Holmium laser and in group B (Cold
      knife group) Sachse cold knife was used. Patients were followed up for 6 months
      after surgery in Out Patient Department on 15, 30 and 180 post-operative days. At
      each follow up visit physical examination, and uroflowmetry was performed along
      with noting complaints, if any. RESULTS: The peak flow rates (PFR) were compared
      between the two groups on each follow up. At 180 days (6 month interval) the
      difference between mean of PFR for Holmium and Cold knife group was statistically
      highly significant (P < 0.001). Complications were seen in 12.22% of cases.
      CONCLUSION: Both modalities are effective in providing immediate relief to
      patients with single and short segment (<2 cm long) urethral strictures but more
      sustained response was attained with Cold knife urethrotomy.

PMID- 25371613
TI  - Analysis of case series of milky urine: A single center and departmental clinical
      experience with emphasis on management perspectives: A prospective observational
      study.
AB  - BACKGROUND: Milky urine can be due to chyluria or lipiduria due to nephrotic
      syndrome. Filarial chyluria usually responds to medical management while non
      filarial cases may require surgical intervention. AIM: To perform a prospective
      observational study in patients presenting with milky urine in our centre over a
      period of one year from July 2011 to June 2012, a complete biochemical work up
      and imaging to find out the site of leakage of lymph if it is a case of chyluria,
      its response to medical management and the requirement of surgical intervention.
      MATERIALS AND METHODS: Routine blood and urine investigations, 24 hour urine
      protein excretion, USG abdomen, serum lipid profile and rapid filarial antigen
      test were done in all. MRI abdomen was done in affordable patients. Renal biopsy
      was done in some chyluria patients for academic purpose and in milky urine with
      negative urine ether test. Sclerotherapy was done with 50% dextrose and 0.2%
      povidone iodine. Patients were followed up with 24 hour urine protein and
      triglyceride estimation. RESULTS: 18 cases of milky urine were encountered. 8
      were filarial chyluria, 9 non- filarial and 1 MCD. Mean urine TG level and median
      24 hour urinary protein excretion were 37.2 +/- 24.6 mg% and 4.96 g respectively.
      The mean age for filariasis (22.9 +/- 4.5 years) was significantly different from
      that of non-filarial etiology (31.5 +/- 4.8 years) (P = 0.005). The mean 24 hour
      urinary protein for normal MRI cases (4.64 +/- 0.70 g) was significantly
      different from those with dilated lymphatics (8.15 +/- 2.55 g) (P = 0.02). All
      the non- filarial and 4 filarial cases required sclerotherapy. One patient
      required a second sitting. CONCLUSION: Milky urine is most commonly due to
      chyluria and occasionally due to nephrotic syndrome. Nephrotic syndrome is
      managed in its own way while chyluria not amenable to pharmacological
      intervention is managed with sclerotherapy.

PMID- 25371612
TI  - Day care monopolar transurethral resection of prostate: Is it feasible?
AB  - INTRODUCTION: Benign prostatic hyperplasia is a common disease accounting for 30%
      of our OPD cases and about 25% of our surgery cases. Various treatment options
      are now available for more efficient care and early return to work. We wanted to
      determine the safety and feasibility of day care monopolar transurethral
      resection of prostate (m-TURP), by admitting the patients on the day of surgery
      and discharging the patient without catheter on the same day. We also compared
      the morbidity associated with conventional TURP where in the catheter is removed
      after 24-48 h of surgery and day care TURP where in the catheter is removed on
      the day of surgery. MATERIALS AND METHODS: A total of 120 patients who fulfilled
      the criteria were included in the study which was conducted between November 2008
      and December 2010. A total of 60 patients were assigned for day care and 60 for
      conventional monopolar TURP. There was no significant difference in age,
      prostatic volume or IPSS score. Day care patients were admitted on day of surgery
      and discharged the same day after the removal of catheter. RESULTS: Both the
      groups were comparable in outcome. Stricture rate was less with day care TURP.
      Mean catheterization time was similar to laser TURP. CONCLUSION: Monopolar TURP
      is still the gold standard of care for BPH. If cases are selected properly and
      surgery performed diligently it remains the option of choice for small and medium
      sized glands and patients can be back to routine work early.

PMID- 25371614
TI  - Efficacy of extracorporeal shockwave lithotripsy using Dornier SII in different
      levels of ureteral stones.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of
      the Dornier lithotripter S II system in the treatment of ureteral calculi.
      PATIENTS AND METHODS: A total of 97 cases which consists of 54 males and 43
      females with ureteral stones were treated by extracorporeal shock wave
      lithotripsy (ESWL). Mean age was 42.6 years. Inclusion criteria were solitary
      radiopaque ureteral stones of radiological stone size of <=1 cm. The stones were
      not impacted, with normal kidney functions. Procedure time, number of shocks,
      energy used, number of sessions and complications were reported. The outcome of
      ESWL was also recorded. RESULTS: Stones were in the abdominal (upper ureter) in
      50% of patients, in pelvic (middle ureter) in 47% of patients. All patients had
      unilateral stones and the mean stone size in maximum length was) 10 mm). Good dye
      excretion passing the stone was noted in all patients. Mild hydronephrosis was
      found in 85% of cases. A total of 49 cases were treated by a single session,
      while in 35% of cases two sessions were enough and 16% received three sessions.
      The average number of shocks per session was 3125. The average number of shocks
      per patient was 5962.5 shocks and average energy was 204.3 Joules. The overall
      stone-free rate 3 months after lithotripsy was 94%. After a single session of
      lithotripsy, 49 patients (49%) became stone-free. Stone free rates after ESWL for
      upper, middle ureteral stones were 94%, 95.7% respectively. Additional procedures
      were needed in only 6 cases (6%) to render patients stone-free after lithotripsy.
      No serious complications occurred. CONCLUSION: The Dornier lithotripter S II is
      very effective in the treatment of ureteral calculi with no major complications.

PMID- 25371615
TI  - Modified medial nephropexy for treatment of the anterior nutcracker syndrome.
AB  - We report the case of a 15-year-old male, presenting with recurrent gross
      hematuria complicated by acute anemia. Cystoscopy showed little bleeding from the
      left ureteral orifice. Diagnosis of left renal vein compression at the
      aortomesenteric space was established through color Doppler ultrasonography and
      computed tomographic angiography. Therapeutic attitude was interventionist in our
      case, performing successful management with modified medial nephropexy, with a
      retroperitoneal approch. To the best of our knowledge, we report the second case
      of left medial nephropexy for treatment of the anterior nutcracker syndrome. The
      first case of modified medial nephropexy was done by lowering the left renal vein
      from its initial position in the aortomesenteric angle through a restrict
      retroperitoneal approach. 

PMID- 25371616
TI  - Leiomyoma of the epididymis treated with partial epididymectomy.
AB  - Tumors of the epididymis are very rare, they are both primary and secondary and
      whether the benign or malignant. Adenomatoid tumors and leiomyoma are the most
      frequently diagnosed benign tumors of the epididymis. Leiomyomas are benign,
      often bulky tumors that are derived embryologically from mesenchymal cells.
      Herein, we present a case of epididymal leiomyoma and review its differential
      diagnosis and treatment. 

PMID- 25371617
TI  - Urinary bladder metastasis from lung adenocarcinoma: A rare cause of hematuria.
AB  - We presented an unusual case of hematuria caused by a solitary bladder metastasis
      from lung adenocarcinoma. A confident diagnosis of secondary adenocarcinoma of
      the bladder was made by clinical suspicion based on patient's past history,
      careful examination of tumor morphology, and a directed panel (cytokeratin [CK]
      7/CK20/thyroid transcription factor 1) of immunohistochemistry. We sought,
      through sharing our experience in the investigative and diagnostic process, to
      contribute to the better understanding of this unusual cause of hematuria. 

PMID- 25371618
TI  - Seminal vesicle schwannoma presenting with left hydroureteronephrosis.
AB  - We report a very rare case of seminal vesicle schwannoma in a 50-year-old male,
      with left hydroureteronephrosis. Only five cases of seminal vesicle schwannomas
      have been reported in medical literature until date. 

PMID- 25371620
TI  - Pregabalin and priapism.

PMID- 25371619
TI  - Priapism associated with pregabalin.
AB  - Priapism is a well-known cause of erectile dysfunction. There are a wide variety
      of causes, including hemoglobinopathy, neurological diseases, and drugs. We
      present a case report of an Asian man who presented with priapism that was
      continuous for 3 days after taking three doses of pregabalin for chronic back
      pain. Cavernous aspiration, phenylephrine injection, and a winter shunt all
      failed to achieve detumescence. The patient then presented to our institution on
      the 5(th) day of his initial presentation, and an El-Ghorab shunt was performed,
      after which detumescence and pain relief were achieved. We suggest that
      pregabalin might induce tumescence through acting on the alpha2delta1 subunit of
      voltage-gated calcium channels in the penile smooth muscle or by presynaptic
      inhibition of noradrenaline release. Further studies are warranted regarding the
      action of pregabalin and its effect on penile physiology. 

PMID- 25371621
TI  - Conservatively managed spontaneous intraperitoneal bladder perforation in a
      patient with chronic bladder outflow obstruction.
AB  - We present the unusual case of a spontaneous intraperitoneal bladder rupture as a
      first presentation of chronic bladder outflow obstruction secondary to benign
      prostatic hyperplasia. A contributing factor to diagnostic delay was
      unfamiliarity with the classical presentation of abdominal pain, abdominal
      distension and urinary ascites leading to autodialysis represented by an
      unusually high serum creatinine. A cystogram was performed after a non-contrast
      computed tomography (CT) scan originally performed to determine the cause of
      abdominal pain, failed to confirm the diagnosis. The patient's initial acute
      presentation was successfully managed conservatively with prolonged urinary
      catheterization. 

PMID- 25371622
TI  - Extensive xanthogranulomatous cystitis mimicking bladder cancer.
AB  - Xanthogranulomatous cystitis (XC) is a rare benign disease of unknown etiology. A
      39-year-old female presented with 2 month history of urgency, dysuria, lower
      abdominal mass. On physical examination a hard hypogastric mass was present fixed
      to the rectus muscle. Computerized tomography (CT) abdomen showed heterogeneous
      enhancing mass arising from the anterior bladder wall with infiltration of the
      overlying parietal wall. Cystoscopy revealed extensive growth involving the
      entire wall of the bladder. A biopsy showed cystitis with focal areas suggestive
      of urothelial neoplasia of unknown malignant potential. Suspecting bladder
      cancer, we proceeded with radical cystectomy with ileal conduit. Histopathology
      revealed cystitis cystica with XC of the entire bladder. This is, to our
      knowledge, the first time that a case has been found to be so extensive with
      infiltration of the parietal wall and second time that radical cystectomy has
      been performed for XC. 

PMID- 25371623
TI  - Challenges in the diagnosis of xanthogranulomatous cystitis.

PMID- 25371624
TI  - Enucleation/partial nephrectomy for large mixed epithelial stromal tumor and
      herniating into the pelvicalyceal system.
AB  - OBJECTIVES: Mixed Epithelial and Stromal Tumor of the kidney is an adult renal
      neoplasm. It is mostly benign in nature. Typically it is composed of a mixture of
      epithelial and mesenchymal components. We hereby report on the feasibility of
      performing partial nephrectomy/enucleation for Huge Mixed Epithelial Stromal
      Tumor of the kidney without sacrificing the involved renal unit even in the
      tumors herniating into the collecting system. METHODS: Two female patients on
      long term hormonal therapy developed large enhancing multiloculated and septated
      renal masses. Kidney mass size was 18.5 cms in one patient and 11.5 in the
      second. In one patient, the mass was herniating into the collecting system. Both
      patients had enucleation/partial nephrectomy. RESULTS: Enucleation and partial
      nephrectomy were successfully performed in both patients. In the patient with the
      mass herniating into the collecting system, the horns of the mass herniating into
      the collecting system were easily enucleated with repair of the collecting system
      and salvage of the involved renal unit. Post op pathology revealed MEST in both
      patients. There were no intraoperative or postoperative complications.
      CONCLUSIONS: Enucleation and partial nephrectomy for huge MEST is feasible. Mixed
      Epithelial Stromal Tumor herniating into the pelvicalyceal system may not warrant
      nephroureterectomy as previously reported.

PMID- 25371625
TI  - A bone fide atypical fibroxanthoma of penis.
AB  - Malignant mesenchymal tumors of the penis are very rare and they have vascular
      origin. We present a case of a 71-year-old man with a painless nodule of 2.0 cm
      in diameter located in the penile foreskin. There was no history of urinary or
      sexually transmitted disease. An excisional biopsy revealed a markedly
      pleomorphic sarcoma resembling atypical fibroxanthoma (AFX) associated with a
      squamous cell carcinoma in situ. The patient refused a wide re-excision and was
      free of disease after 36 months. Because the different therapeutic management and
      prognosis, differential diagnosis should be made with sarcomatoid squamous cell
      carcinoma and melanoma: A diagnosis of AFX or malignant fibrous histiocytoma may
      be considered only after the complete exclusion of these two entities. 

PMID- 25371626
TI  - Prostatic melanosis.
AB  - Prostatic melanosis is a very rare, benign lesion characterized by the presence
      of melanin in the epithelium of the prostate gland and stromal dendritic cells,
      requiring no additional treatment. It constitutes the melanocytic lesions of the
      prostate together with blue nevus and malignant melanoma. We present a case with
      prostatic melanosis because it is rarely seen and its distinction from malignant
      melanoma is clinicopathologically very important. 

PMID- 25371627
TI  - Plasma cell granuloma of the urinary bladder: A pseudotumor - A clinical dilemma.
AB  - Plasma cell granuloma is a rare benign proliferative lesion that often mimics a
      malignant mass clinically and radiologically and its presentation in the urinary
      bladder is exceptional. Presuming malignant mass, such lesions often receive
      radical treatment. We are presenting here one such tumor, which resembled as an
      urachal tumor and underwent partial cystectomy. 

PMID- 25371628
TI  - Inflammatory pseudotumor of urinary bladder: Beware lest we forget.

PMID- 25371629
TI  - Urethrocutaneous fistula following fracture penis.
AB  - Penile fracture is an emergency in urology. Early surgical management is
      recommended, to prevent long term complications. Although urethrocavernosal
      fistula is one of the described complications following fracture penis repair in
      literature, no case of urethrocuteneous fistula has been reported till now. Here
      we report the first case of urethrocutaneous fistula following repair of fracture
      penis. 

PMID- 25371630
TI  - Urethrocutaneous fistula following penile fracture.

PMID- 25371631
TI  - Last issue of 2014: interesting assortment of ocular pathology.

PMID- 25371632
TI  - Pattern of uveitis at a referral center in Iraq.
AB  - PURPOSE: To determine the etiologies of uveitis and the causes of visual loss in
      uveitis patients at a referral center in Baghdad, Iraq. PATIENTS AND METHODS: A 4
      year prospective study was performed at the uveitis clinic at Ibn Al-Haetham
      teaching eye hospital in Baghdad, Iraq. Referral cases of active uveitis were
      included. A complete ophthalmic examination was performed in all cases. If
      clinical picture did not indicate a specific etiology, patients were sent for a
      routine set of tests while ancillary tests were conducted when indicated.
      RESULTS: Out of 318 patients included in this study, 236 patients (74.2%) had
      bilateral uveitis, and 212 patients (66.7%) had non-granulomatous uveitis.
      Posterior uveitis was recorded in 123 cases (38.7%) followed by panuveitis in 97
      cases (30.5%), anterior uveitis in 78 cases (24.5%), and intermediate uveitis in
      20 cases (6.3%). A diagnosis was established in 210 cases (66%) while etiology
      could not be determined in the remaining 108 cases (34%). Most common infectious
      causes were toxoplasmosis (13.8%) and presumed ocular tuberculosis (11.4%) while
      most common non-infectious causes were Vogt-Koyanagi-Harada disease (12.3%),
      Behetaet's disease (8.2%), and pars planitis (5.7%). Out of 49 eyes with
      irreversible blindness, macular degenerations, or scars (46.9%) and optic nerve
      atrophy (34.7%) were the most important causes. CONCLUSION: At this referral
      center, toxoplasmosis and presumed ocular tuberculosis were the most common
      infectious causes of uveitis while Vogt-Koyanagi-Harada disease, Behetaet's
      disease, and pars planitis were, in that order, the most common non-infectious
      causes. Macular degenerations or scars and optic nerve atrophy were the most
      important causes of irreversible blindness.

PMID- 25371633
TI  - Comparative evaluation between ranibizumab combined with laser and bevacizumab
      combined with laser versus laser alone for macular oedema secondary to branch
      retinal vein occlusion.
AB  - PURPOSE: To evaluate the anatomical and functional efficacy of combination
      therapy of intravitreal ranibizumab with laser or intravitreal bevacizumab with
      laser treatment compared to only laser treatment for macular edema due to branch
      retinal vein occlusion (BRVO). MATERIALS AND METHODS: Thirty eyes of 30 patients
      with BRVO of at least 6 weeks duration were randomized into three groups: Group 1
      received a single dose of intravitreal Ranibizumab followed by grid laser
      treatment, Group 2 received a single dose of intravitreal Bevacizumab followed by
      grid laser treatment, and Group 3 received grid laser alone. Outcomes at 6 months
      follow-up were reported. Data were collected on best corrected visual acuity
      (BCVA), central foveal thickness (CFT), and gain in lines of Snellen acuity.
      RESULTS: At 6 month follow-up, the difference in the mean BCVA and CFT between
      the three treatment groups was not statistically significant (P > 0.05, all
      comparisons). Six eyes (60%) in Group 1, four eyes (40%) in Group 2 and two eyes
      (20%) in Group 3 had a statistically significant gain of >=3 lines of Snellen
      acuity (P < 0.05). CONCLUSION: Both ranibizumab and bevacizumab combined with
      laser photocoagulation, resulted in better outcomes than grid laser treatment.

PMID- 25371634
TI  - Optical coherence tomography of fovea before and after laser treatment in
      retinopathy of prematurity.
AB  - PURPOSE: To study the fovea in preterm babies with Type I retinopathy of
      prematurity (ROP) before and after laser treatment using optical coherence
      tomography (OCT). MATERIALS AND METHODS: This was a prospective observational
      case-control study including preterm neonates undergoing screening for ROP from
      May 2009 to July 2011. Group 1 included 30 eyes of 15 neonates with Type I ROP. A
      532-nm laser was used for treatment in all cases for Group 1. Group 2 included 14
      eyes of 7 preterm neonates without ROP that served as controls. OCT was performed
      under sedation in the lateral position before and after laser treatment. P <0.05
      was considered statistically significant. RESULTS: The mean initial central
      macular thickness (CMT) was comparable in both groups (P = 0.832) and
      statistically significantly correlated with gestational age (P = 0.015). No
      adverse effects on the anterior segment or posterior segment were observed. There
      was no significant difference in CMT before and after laser treatment in Group 1
      (P = 0.007). There was one case of cystoid macular edema after laser treatment.
      CONCLUSION: The macula in preterm babies with Type 1 ROP was comparable to those
      without ROP. Gestational age was the only predictor of CMT.

PMID- 25371635
TI  - Effect of anterior chamber depth on the choice of intraocular lens calculation
      formula in patients with normal axial length.
AB  - PURPOSE: To compare the accuracy of  Sanders-Retzlaff-Kraff II (SRK II) and 3(rd)
      and 4(th) generation intraocular lens (IOL) formulas and to compare the effect of
      different anterior chamber depths among the IOL formulas in cataract patients
      with normal axial length (AL; 22.0-24.5 millimeters, mm). MATERIALS AND METHODS:
      A retrospective chart review was performed of patients with normal AL who
      underwent cataract surgery. The SRK II and 3(rd) generation IOL formulas (Hoffer
      Q, SRK T, Holladay 1) were compared to the 4(th) generation Haigis formula. For
      analysis, preoperative anterior chamber depth (ACD) was divided into three
      subgroups: <=3, 3-3.5, and >= 3.5 mm. The mean error (ME) and mean absolute error
      (MAE) of each formula was compared for each subgroup against the total. The
      difference between the ME and MAE of the formulas were compared for each ACD
      subgroup. P < 0.05 was considered statistically significant. RESULTS: The study
      sample was comprised of 309 eyes. The MAE were 0.56 D, 0.52 D, 0.51 D, 0.50 D,
      and 0.50 D with Haigis, Hoffer Q, SRK T, Holladay 1, and SRK II formulas,
      respectively. The Haigis formula was a significantly weaker predictor than the
      SRK T (P < 0.001) and Holladay 1 (P = 0.035) formulas. The ME with Haigis formula
      was -0.23 D which changed to -0.06 D with ACD >= 3.5 mm (P = 0.002). The ME was 
      0.24 D with SRK II and changed to -0.09D with ACD <= 3 mm (P = 0.004). There was
      no statistically significant difference between Hoffer Q, SRK T, and Holladay
      formulas 1 in ACD subgroups (P > 0.05, all comparisons). CONCLUSION: The SRK II
      formula can predict refraction in patients with normal AL and ACD less than 3 mm
      with less error and is preferred over other formulas. The Haigis formula is the
      preferred choice in patients with a normal AL and ACD longer than 3.5 mm. The
      prediction accuracy of Hoffer Q, SRK T, and Holladay 1 is comparable in normal
      AL.

PMID- 25371636
TI  - Ocular dirofilariasis: a case series of 8 patients.
AB  - PURPOSE: Dirofilaria repens is an endemic parasite in Mediterranean countries
      that mostly affects animals. Rarely, however, it can infect humans. This case
      series presents patients with ocular infections due to D. repens. MATERIALS AND
      METHODS: A chart review was performed of patients with ocular dirofilariasis
      after the year 2000, treated at a tertiary referral centre in Greece. Data were
      collected on the ocular, microbiological, or/and histopathological aspects and
      treatment. RESULTS: Eight cases of unilateral ocular dirofilariasis were
      identified, of which 5 were subconjunctival (1 masquerading as nodular scleritis)
      and were removed through a conjunctival incision, 2 cases were intravitreal and
      were removed with vitrectomy, and 1 was intraorbital (adjacent to the roof of the
      orbit). The latter appeared as an encapsulated mass and subsequent histological
      examination revealed the presence of the parasite. Of the 8 cases recorded after
      the year 2000, 7 appeared within the last 6 years (4 cases within the last 3
      years). The majority of cases involved residents of the Ionian Islands (7 of 8
      cases). CONCLUSIONS: D. repens can affect various ocular and periocular tissues.
      A progressive increase in the incidence of dirofilariasis was observed, which is
      potentially associated with climate changes in warm and moist areas where this
      parasite is endemic.

PMID- 25371637
TI  - Blepharitis: always remember demodex.
AB  - PURPOSE: To determine the incidence and density of Demodex species on the
      eyelashes of subjects with normal eyelids, anterior blepharitis (AB), meibomian
      gland dysfunction (MGD), and mixed blepharitis (MB). MATERIALS AND METHODS: One
      hundred and fifty consecutive patients diagnosed with AB, MGD, and MB were
      recruited. An additional 50 individuals were recruited who were free of lid and
      margin disease to serve as a control group. All patients underwent a standard eye
      examination. Data on ocular symptomatology were gathered. Digital photography was
      performed of the lid margins. Lash sampling was performed by epilating the lashes
      and the lashes were checked for Demodex based on morphology using light
      microscopy. The total number of mites were tabulated for each eye. Comparison
      between the affected eyes and the control eyes was performed. Data were analyzed
      using the Chi-square test. RESULTS: A total of 200 patients were included. Twenty
      percenth had AB, 40% had MGD, and 40% had MB. The incidence of Demodex
      infestation was 90% in cases of AB, 60% in MGD cases, and 90% in MB cases. The
      incidence of Demodex in control subjects was 18%. CONCLUSIONS: The incidence and
      density of Demodex infestation was highest in patients with AB and MB. Lid
      irritation and presence of cylindrical dandruff were indicative of a high-density
      infestation. These signs should alert the clinician to treat concomitant Demodex
      infestation.

PMID- 25371638
TI  - Retinoblastoma referral pattern in Kenya.
AB  - PURPOSE: Kenya is a large country with a widely dispersed population. As
      retinoblastoma requires specialized treatment, we determined the referral pattern
      for patients with retinoblastoma in Kenya to facilitate the formulation of a
      national policy. MATERIALS AND METHODS: A retrospective study was performed for
      retinoblastoma patients who presented from January 1, 2006 to December 31, 2007.
      Data were collected on the referral process from presenting health facility to
      the hospital where patient was treated. Data were also collected on the time
      interval when the first symptoms were noticed to the time of presentation at a
      health facility (lag time). For cases that could be traced to a referral
      hospital, the time delay due to referral (referral lag time) was recorded.
      RESULTS: There were 206 patients diagnosed with retinoblastoma in 51 Kenyan and 2
      foreign healthcare facilities, and they received final treatment at a Kenyan
      hospital. Mean lag time was 6.8 months (+/-6.45). Of all patients, 18% (38/206)
      were treated at the hospital where they first presented and 82% (168/206) were
      referred elsewhere. Of those referred, 35% (58/168) were lost to follow-up. The
      mean referral lag time was 1.7 months (+/-2.5). CONCLUSIONS: A significant
      proportion of cases presented late, and either delayed seeking further treatment
      or were lost after initial referral. We recommend the implementation of a
      national strategy that emphasizes early detection, documentation and follow up of
      retinoblastoma patients.

PMID- 25371639
TI  - Effects of fasting on intraocular pressure in a black population.
AB  - INTRODUCTION: There is a dearth of literature available on the effects of fasting
      on Intraocular pressure (IOP) among all races and worldwide. OBJECTIVES: To
      determine the effects of fasting on IOP in a black African population. MATERIALS
      AND METHODS: A population-based survey utilizing multistage random sampling
      techniques was carried out among healthy adult Muslims who were examined before
      and during Ramadan fast in Osogbo, Nigeria. Demographics were obtained, visual
      acuities, clinical examination of both eyes, and IOPs were done. Weights and
      waist circumference were measured. Data were analyzed using Statistical Package
      for Social Sciences ( SPSS) Version 16. Analysis generated frequencies and cross
      tabulations, whereas statistical significant values were derived using paired
      sample t-test and P < 0.05. RESULTS: A total of 60 subjects with 120 eyes were
      examined. Mean age was 42.3 years standard deviation (SD) 16.7, and the male to
      female ratio was 3:2. Majority were professionals (33.3%). Only 18.3% had less
      than secondary school education. Over 90% had normal vision (6/5-6/18). Before
      and during fasting, the mean weights were 65.92 kg SD 12.98 and 65.29 kg SD 12.41
      with a reduction of 0.63 kg SD 3.82 (P = 0.214, 95% confidence interval (CI):
      0.372-1.626); and the mean waist circumference was 87.20 cm SD 12.39 and 81.78 cm
      SD 11.65 (P = 0.000, 95% CI 4.128-6.720), respectively. Mean IOPs were 15.98 mmHg
      SD 3.11 and 14.08 mmHg SD 2.71 before and during fasting, respectively (P =
      0.000, 95% CI 0.98558-2.82798). CONCLUSIONS: The study shows that fasting
      significantly reduced IOP in an ocularly healthy black African population.

PMID- 25371640
TI  - Prevalence of chronic ocular complications in Stevens-Johnson syndrome and toxic
      epidermal necrolysis.
AB  - PURPOSE: The aim of this study is to identify and grade the severity of chronic
      ocular complications in patients who suffered from Stevens-Johnson syndrome (SJS)
      and toxic epidermal necrolysis (TEN) treated in Cape Town, South Africa. METHODS:
      A total of 54 patients with SJS or TEN for 6 months or longer were examined. The
      ocular complications were classified into corneal, eyelid and conjunctival
      complications. The complications were graded from 0 to 3 depending on the
      severity. RESULTS: A total of 108 eyes were included in the study. Medications
      caused SJS or TEN in all cases, and the most common associated drugs were anti
      retroviral medications. 59.3% of patients were HIV-positive, with CD4 counts
      ranging from 6 to 521. Although only 11% of patients with SJS or TEN had acute
      ocular complications during the initial illness, 89% developed chronic ocular
      complications. Loss of the palisades of Vogt was the most common corneal
      complication. Among the six components of conjunctival and eyelid complications,
      irregularity of the mucocutaneous junction abnormalities was the most common,
      followed by mild conjunctival hyperemia. There was no statistically significant
      difference in the severity of chronic ocular complications between HIV-positive
      and HIV-negative patients (P = 0.4). In addition, the severity of chronic ocular
      complications was not statistically significantly associated with visual acuity
      loss (P = 0.3). CONCLUSION: We conclude that almost 90% of patients who are
      diagnosed with SJS or TEN will develop chronic ocular complications. Unless
      eyelids are severely affected, most chronic complications are mild to moderate
      ocular surface abnormalities and not necessarily vision-threatening
      complications.

PMID- 25371642
TI  - Colloid cyst of the third ventricle presenting with features of Terson's
      syndrome.
AB  - This report describes a middle-aged man presenting to the ophthalmologist with
      history of seeing floaters before both eyes since 2-weeks duration. A history of
      intermittent headache and dizziness of recent onset was elicited on questioning.
      Ocular examination showed bilateral early papilloedema and mild vitreous
      hemorrhage. Brain computed tomography (CT) disclosed features suggestive of
      colloid cyst of the third ventricle in the region of foramen of Monro with
      moderate hydrocephalus. Emergency craniotomy and excision of the cyst was done,
      and the patient is doing well for the last 18 months after the surgical
      intervention. The mechanism of this presentation, importance of early
      investigations, and timely intervention are highlighted in order to avoid serious
      neurological sequelae. The literature was extensively reviewed for atypical
      presentations of intraventricular colloid cyst.

PMID- 25371641
TI  - The status of childhood blindness and functional low vision in the Eastern
      Mediterranean region in 2012.
AB  - Childhood blindness and visual impairment (CBVI) are major disabilities that
      compromise the normal development of children. Health resources and practices to
      prevent CBVI are suboptimal in most countries in the Eastern Mediterranean Region
      (EMR). We reviewed the magnitude and the etiologies of childhood visual
      disabilities based on the estimates using socioeconomic proxy indicators such as
      gross domestic product (GDP) per capita and <5-year mortality rates. The result
      of these findings will facilitate novel concepts in addressing and developing
      services to effectively reduce CBVI in this region. The current study determined
      the rates of bilateral blindness (defined as  Best corrected visual acuity(BCVA))
      less than 3/60 in the better eye or a visual field of 10 degrees  surrounding
      central fixation) and functional low vision (FLV) (visual impairment for which no
      treatment or refractive correction can improve the vision up to >6/18 in a better
      eye) in children <15 years old. We used the 2011 population projections, <5-year
      mortality rates and GDP per capita of 23 countries (collectively grouped as EMR).
      Based on the GDP, we divided the countries into three groups; high, middle- and
      low-income nations. By applying the bilateral blindness and FLV rates to high,
      middle- and low-income countries from the global literature to the population of
      children <15 years, we estimated that there could be 238,500 children with
      bilateral blindness (rate 1.2/1,000) in the region. In addition, there could be
      approximately 417,725 children with FLV (rate of 2.1/1,000) in the region. The
      causes of visual disability in the three groups are also discussed based on the
      available data. As our estimates are based on hospital and blind school studies
      in the past, they could have serious limitations for projecting the present
      magnitude and causes of visual disabilities in children of EMR. An effective
      approach to eye health care and screening for children within primary health care
      and with the available resources are discussed. The objectives, strategies, and
      operating procedures for child eye-care are presented. Variables impacting proper
      screening are discussed. To reach the targets, we recommend urgent implementation
      of new approaches to low vision and rehabilitation of children.

PMID- 25371643
TI  - An unusual ocular emergency in severe dengue.
AB  - Dengue, one of the most common mosquito-borne flavivirus diseases affecting
      humans, is spread by the Aedes aegypti mosquito. Most people infected with dengue
      virus are asymptomatic or only have mild symptoms such as an uncomplicated fever;
      few have more severe features, while in a small proportion it is life
      threatening. Severe dengue is defined as that associated with severe bleeding,
      severe organ dysfunction, or severe plasma leakage. Ophthalmic manifestations can
      involve both the anterior and posterior segment. We report an ocular emergency of
      proptosis and globe rupture in a patient with severe dengue. 

PMID- 25371644
TI  - Postoperative necrotizing scleritis: a report of four cases.
AB  - Postoperative necrotizing scleritis should be considered in cases of persistent
      localized postoperative inflammation following all forms of surgical trauma. We
      present the history, clinical findings, and follow-up data of four patients with
      postoperative necrotizing scleritis. The clinical records of four patients who
      developed scleritis following ocular surgery were retrospectively reviewed. The
      first step in managing necrotizing scleritis is to rule out infectious etiology.
      Surgically induced necrotizing scleritis is an immune-mediated condition that can
      coexist with concomitant infectious condition, i.e. endophthalmitis, but response
      to immunosuppression leads to resolution of the disease and verifies the
      diagnosis.

PMID- 25371645
TI  - Multimodal imaging for the diagnosis of an atypical case of central serous
      chorioretinopathy.
AB  - We report a case of a 52-year-old woman presented with atypical central serous
      chorioretinopathy (CSCR) that had been misdiagnosed as posterior uveitis and
      treated with systemic corticosteroids and immunosuppressive therapy, with
      subsequent severe chorioretinal damage. Diagnosis was straightened through
      multimodal imaging. Anatomical improvement was achieved after discontinuation of
      corticosteroids and intravitreal injection of bevacizumab. However, visual acuity
      remained severely impaired in one eye. Failure to differentiate atypical CSCR
      from inflammatory chorioretinal diseases may lead to severe and irreversible
      visual impairment. Multimodal imaging helps recognition of the atypical
      presentations of CSCR, avoiding misdiagnosis and inappropriate management.

PMID- 25371646
TI  - Failure of globe conservation in a case of adult onset retinoblastoma.
AB  - Adult onset retinoblastoma is a rare intraocular malignancy. The majority of the
      cases are treated with enucleation, due to late presentation and advanced-stage
      tumors. Here we report a case of a 30-year-old female who presented with an
      intraocular mass with exudative retinal detachment in her right eye. B-scan
      ultrasound and magnetic resonance imaging (MRI) confirmed the diagnosis of
      retinoblastoma. In an attempt to salvage the globe, she was treated with
      chemotherapy, which resulted in excellent regression of the tumor mass by the end
      of 8 months follow-up. The patient was followed-up regularly with focal treatment
      whenever necessary. Two years later, she developed a massive recurrence
      necessitating enucleation. Histopathologic examination revealed a moderately
      differentiated retinoblastoma with choroidal invasion. Attempt to salvage the
      globe in adult onset retinoblastoma with chemoreduction and focal therapy may be
      possible; however, regular long-term follow-up is necessary for recurrence which
      warrants timely intervention.

PMID- 25371647
TI  - Intracorneal rhinosporidiosis managed with deep anterior lamellar keratoplasty.
AB  - A healthy 22-year-old male presented to Institutional Cornea Clinic with an
      intracorneal mass overlying the pupil with lobulated edges having many tiny
      greyish white dots. The patient had a history of trauma while swimming in a pond
      with subsequent removal of intracorneal foreign body in the left eye
      approximately a year prior to presentation. Anterior segment optical coherence
      tomography (OCT) confirmed that an intracorneal mass sparing deep stroma and
      Descemet's membrane. A deep anterior lamellar keratoplasty (DALK) was performed
      in left eye and the mass was sent for histology examination. Histology evaluation
      was suggestive of rhinosporidiosis. The patient achieved 20/60 BCVA with -1.25
      Chi* 120 degrees  1 year postoperatively without any evidence of recurrence at
      the graft-host interface. This unique presentation (as an 'intracorneal mass') of
      ocular rhinosporidiosis emphasizes that clinicians from our region of the world
      must consider rhinosporidiosis in the differential diagnosis especially with a
      history of penetrating injury while swimming in pond or river water.

PMID- 25371648
TI  - Glass wool tripod foreign bodies in the eye: first ever reported case series.
AB  - We present three cases of unusual corneal/conjunctival foreign bodies that were
      not visible on standard slit lamp examination. All patients presented with
      complaints of foreign body sensation in the affected eyes. One patient had
      visited an ophthalmologist prior to presentation to our center and was diagnosed
      and treated for conjunctivitis. On slit lamp examination minimal congestion was
      seen hence, all the patients were diagnosed with conjunctivitis with corneal
      epithelial defects by the residents. However, because the patients complained of
      foreign body sensation, fluorescein staining of the affected eye was performed.
      On examination, the corneas had epithelial defects and linear scratch marks. We
      suspected a foreign body in upper palpebral conjunctiva (UPC). Examination after
      eyelid eversion indicated tripod-shaped glassy foreign bodies embedded deep
      within the UPC. We present cases of an unusual type of glassy tripod-shaped
      foreign body which may go undetected even on slit lamp examination. Fluorescein
      staining may aid in the detection of these foreign bodies. 

PMID- 25371649
TI  - Primary and secondary implantation of scleral fixated intraocular lens in adult
      patients.

PMID- 25371650
TI  - Author's Reply.

PMID- 25371651
TI  - Preparation and Characterization of Homopolymer Polyacrylonitrile-Based Fibrous
      Sorbents for Arsenic Removal.
AB  - This research investigated the modification of homopolymer polyacrylonitrile
      (PAN) fibers for use as an adsorbent for removing arsenic from drinking water.
      Fibers were chemically modified and cross-linked using combinations of hydrazine
      hydrate and sodium hydroxide (NaOH) before being loaded with ferric hydroxide
      using two different iron loading procedures. Effects of reagent concentrations
      and reaction times on degree of chemical modification and fiber properties were
      investigated using Fourier transform infrared spectroscopy and ion-exchange
      measurements. Arsenate adsorption was a function of both the iron loading and the
      properties of the underlying fiber. For fibers treated with only a single
      reagent, both Fe3+ and arsenate adsorption could be understood in terms of ion
      exchange properties of the fiber surfaces. However, for fibers treated with both
      hydrazine and NaOH, the ion-exchange properties of the surface could not explain
      the Fe3+ and arsenate adsorption behavior. The best arsenate removal performance
      was obtained using the simplest pretreatment procedure of soaking in 10% NaOH at
      95 degrees C for 90 min, followed by precipitation coating of ferric hydroxide.
      This simple preparation procedure involves only two commonly available and
      inexpensive reagents and can be carried out without any specialized equipment.
      This suggests that adsorbents based on inexpensive homopolymer PAN fabric may be
      produced in developing areas of the world where commercial products may not be
      available.

PMID- 25371652
TI  - Recovery of SO2 and MgO from By-Products of MgO Wet Flue Gas Desulfurization.
AB  - An industrial demonstration unit using natural gas as a heat source was built to
      calcine the by-products of MgO wet flue gas desulfurization from power plants;
      influencing factors on the SO2 content in calciner gas were comprehensively
      analyzed; and an advantageous recycling condition of MgO and SO2 from by-products
      was summarized. Results showed that the SO2 content in the calciner gas was
      increased by more than 10 times under a lower excess air coefficient, a higher
      feed rate, a lower crystal water in by-products, and a higher feed port position.
      For the tests conducted under the excess air coefficient above and below one, the
      effect of the furnace temperature on the SO2 content in the calciner gas was
      reversed. Results of activity analysis indicate that particles of MgO generated
      under the calcination temperature of 900-1,000 degrees C had a high activity. In
      contrast, due to the slight sintering, MgO generated under the calcination
      temperature of 1,100 degrees C had a low activity. To recycle SO2 as well as MgO,
      a temperature range of 900-927 degrees C for TE103 is proposed. These studies
      will prompt the desulfurization market diversification, reduce the sulfur's
      dependence on imports for making sulfuric acid, be meaningful to balance the
      usage of the natural resource in China, and be regarded as a reference for the
      development of this technology for other similar developing countries.

PMID- 25371653
TI  - Gender Differences in Musculoskeletal Lipid Metabolism as Assessed by Localized
      Two-Dimensional Correlation Spectroscopy.
AB  - Gender differences in lipid metabolism are poorly understood and difficult to
      study using conventional approaches. Magnetic resonance spectroscopy (MRS)
      permits non-invasive investigation of lipid metabolism. We employed novel two
      dimensional MRS techniques to quantify intramyocellular (IMCL) and
      extramyocellular (EMCL) lipid compartments and their degree of unsaturation in
      normal weight adult male and female subjects. Using muscle creatine (Cr) for
      normalization, a statistically significant (p < 0.05) increase in IMCL/Cr (7.8 +/
      1.6) and EMCL/Cr (22.5 +/- 3.6) for female subjects was observed (n=8), as
      compared to IMCL/Cr (5.9 +/- 1.7) and EMCL/Cr (18.4 +/- 2.64) for male subjects.
      The degree of unsaturation within IMCL and EMCL was lower in female subjects, 1.3
      +/- 0.075 and 1.04 +/- 0.06, respectively, as compared to that observed in males
      (n=8), 1.5 +/- 0.08 and 1.12 +/- 0.03, respectively (p < 0.05 male vs female for
      both comparisons). We conclude that certain salient gender differences in lipid
      metabolism can be assessed noninvasively by advanced MRS approaches.

PMID- 25371654
TI  - Hemodynamic impact of isobaric levobupivacaine versus hyperbaric bupivacaine for
      subarachnoid anesthesia in patients aged 65 and older undergoing hip surgery.
AB  - BACKGROUND: The altered hemodynamics, and therefore the arterial hypotension is
      the most prevalent adverse effect after subarachnoid anesthesia. The objective of
      the study was to determine the exact role of local anesthetic selection
      underlying spinal anesthesia-induced hypotension in the elderly patient. We
      conducted a descriptive, observational pilot study to assess the hemodynamic
      impact of subarachnoid anesthesia with isobaric levobupivacaine versus hyperbaric
      bupivacaine for hip fracture surgery. DESCRIPTION: Hundred twenty ASA status I-IV
      patients aged 65 and older undergoing hip fracture surgery were enrolled. The
      primary objective of our study was to compare hemodynamic effects based on
      systolic blood pressure (SBP) and dyastolic blood pressure (DBP) values, heart
      rate (HR) and hemoglobin (Hb) and respiratory effects based on partial oxygen
      saturation (SpO2%) values. The secondary objective was to assess potential
      adverse events with the use of levobupivacaine versus bupivacaine. Assessments
      were performed preoperatively, at 30 minutes into surgery, at the end of
      anesthesia and at 48 hours and 6 months after surgery. Among intraoperative
      events, the incidence of hypotension was statistically significantly higher (p
      <0.05) in group BUPI (38.3%) compared to group LEVO (13.3%). There was a decrease
      (p <0.05) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at
      30 minutes intraoperatively (19% in group BUPI versus 17% in group LEVO). SpO2%
      increased at 30 minutes after anesthesia onset (1% in group BUPI versus 1.5% in
      group LEVO). Heart rate (HR) decreased at 30 minutes after anesthesia onset (5%
      in group BUPI versus 9% in group L). Hemoglobin (Hb) decreased from time of
      operating room (OR) admission to the end of anesthesia (9.3% in group BUPI versus
      12.5% in group LEVO). The incidence of red blood cell (RBC) transfusion was 13.3%
      in group BUPI versus 31.7% in group LEVO, this difference was statistically
      significant. Among postoperative events, the incidence of congestive heart
      failure (CHF) was significantly higher in group BUPI (8,3%). At 6 months after
      anesthesia, no differences were found. CONCLUSIONS: Given the hemodynamic
      stability and lower incidence of intraoperative hypotension observed,
      levobupivacaine could be the agent of choice for subarachnoid anesthesia in
      elderly patients.

PMID- 25371655
TI  - Epidemiology of dyslipidemia in Chinese adults: meta-analysis of prevalence,
      awareness, treatment, and control.
AB  - BACKGROUND: Numerous epidemiology studies on dyslipidemia have been conducted in
      China. However, a nationally representative estimate for dyslipidemia prevalence
      is lacking. The aim of this study is to appraise the nationwide prevalence,
      awareness, treatment, and control rates of dyslipidemia in adults in China.
      METHODS: We performed a systematic review of the related observational studies
      published since 2003 by searching English and Chinese literature databases. Meta
      analyses were conducted in eligible studies using a random effect model to
      summarize the dyslipidemia prevalence, awareness, treatment, and control rates.
      Heterogeneity and publication bias were analyzed. Sensitivity analyses were
      performed to explain heterogeneity and examine the impact of study quality on the
      results of meta-analyses. RESULTS: Thirty-eight papers were included for meta
      analyses, with a total sample size of 387,825. The prevalence, awareness,
      treatment, and control rates of dyslipidemia were 41.9% (95% CI: 37.7% - 46.2%),
      24.4% (95% CI: 14.4% - 38.4%), 8.8% (95% CI: 7.7% - 10.0%), and 4.3% (95% CI:
      4.1% - 4.5%), respectively. The prevalence of hypercholesterolemia,
      hypertriglyceridemia, mixed hyperlipidemia, low levels of high-density
      lipoprotein cholesterol, and high levels of low-density lipoprotein cholesterol
      were 10.1% (95% CI: 5.8% - 16.9%), 17.7% (95% CI: 14.0% - 22.1%), 5.1% (95% CI:
      3.1% - 8.2%), 11.0% (95% CI: 8.0% - 15.0%), and 8.8% (95% CI: 4.1% - 17.8%),
      respectively. Sensitivity analyses revealed that males had a higher prevalence of
      dyslipidemia (43.2%) than females (35.6%). Study samples of age 30 and above in
      the eastern region tended to have higher prevalence of dyslipidemia. The quality
      of the studies has a slight impact on the pooled estimates. CONCLUSIONS: The
      overall pooled prevalence of dyslipidemia in Chinese adults was estimated to be
      41.9%, with males having a higher rate than females.

PMID- 25371656
TI  - Bone status of children born from mothers with autoimmune diseases treated during
      pregnancy with prednisone and/or low molecular weight heparin.
AB  - BACKGROUND: To evaluate bone status in children born from mothers followed for
      autoimmune diseases and treated during pregnancy with low molecular weight
      heparin (LMVH) and/or prednisone. FINDINGS: History, physical examination,
      laboratory tests and phalangeal ultrasonography were performed. Demographic,
      clinical, and laboratory data were entered into a customized database, and
      results were analyzed with SPSS software. In children whose mothers were treated
      with LMWH, we retrieved dried blood spots taken for newborn screening, and
      analyzed the presence of heparin with tandem mass spectrometry. We enrolled 27
      females and 14 males born from 31 mothers with SLE or connective tissue diseases.
      These women were continuously treated during pregnancy with LMWH (n = 10),
      prednisone (n = 16), or both (n = 15). Bone ultrasound revealed low values (<= 3
      centile for age) in ten patients. In a multistep regression analysis, age at
      examination resulted the single predictor of low ultrasound values (p < 0.004).
      Tandem mass spectroscopy failed to determine traces of heparin in newborn blood.
      CONCLUSIONS: Children born from mothers with autoimmune diseases are at risk to
      develop reduced bone mass. The administration of LMWH and of prednisone seems to
      be safe with regard to children's bone health.

PMID- 25371657
TI  - Synthesis, Characterization, DNA Interaction, and Antitumor Activities of La
      (III) Complex with Schiff Base Ligand Derived from Kaempferol and
      Diethylenetriamine.
AB  - A novel La (III) complex, [LaL(H2O)3]NO3 .3H2O, with Schiff base ligand L derived
      from kaempferol and diethylenetriamine, has been synthesized and characterized by
      elemental analysis, IR, UV-visible, (1)H NMR, thermogravimetric analysis, and
      molar conductance measurements. The fluorescence spectra, circular dichroism
      spectra, and viscosity measurements and gel electrophoresis experiments indicated
      that the ligand L and La (III) complex could bind to CT-DNA presumably via
      intercalative mode and the La (III) complex showed a stronger ability to bind and
      cleave DNA than the ligand L alone. The binding constants (K b ) were evaluated
      from fluorescence data and the values ranged from 0.454 to 0.659 * 10(5) L mol(
      1) and 1.71 to 17.3 * 10(5) L mol(-1) for the ligand L and La (III) complex,
      respectively, in the temperature range of 298-310 K. It was also found that the
      fluorescence quenching mechanism of EB-DNA by ligand L and La (III) complex was a
      static quenching process. In comparison to free ligand L, La (III) complex
      exhibited enhanced cytotoxic activities against tested tumor cell lines HL-60 and
      HepG-2, which may correlate with the enhanced DNA binding and cleaving abilities
      of the La (III) complex. 

PMID- 25371658
TI  - Synthesis, Spectroscopic Characterization, and Biological Evaluation Studies of 5
      Bromo-3-(((hydroxy-2-methylquinolin-7-yl)methylene)hydrazono)indolin-2-one and
      Its Metal (II) Complexes.
AB  - The Schiff base ligand 5-bromo-3-(((8-hydroxy-2-methylquinolin-7
      yl)methylene)hydrazono)indolin-2-one (BHMQMHI) was prepared via condensation of 5
      bromo-3-hydrazonoindolin-2-one and 7-formyl-8-hydroxy-2-methylquinoline and its
      Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) complexes have been
      synthesized and characterized by elemental analysis, conductance data, magnetic
      susceptibility measurements, IR, UV-Vis, mass spectrometry, (1)H NMR, ESR, XRD,
      and thermal studies. By these spectral studies it is found that Co(II), Ni(II),
      and Cu(II) complexes have exhibited octahedral geometry whereas the Zn(II),
      Cd(II), and Hg(II) complexes have exhibited tetrahedral geometry. Potentiometric
      studies have been carried out on complexes of Schiff base (BHMQMHI) with Cu(II),
      Co(II), and Ni(II). Calvin-Bjerrum pH-titration technique as used by Irving and
      Rossotti has been applied to determine stability constants in mixed solvents at
      25 +/- 1 degrees C. The present study reports the protonation constants of this
      ligand and stability constants of its metal complexes in dioxane-water (50%, v/v)
      mixtures. Metal-ligand stability constants fall in the order of Cu(II) > Co(II) >
      Ni(II) which is in agreement with those reported by Irving stability order. The
      Schiff base (BHMQMHI) and its metal complexes have been screened for their in
      vitro antibacterial and antifungal activities by minimum inhibitory concentration
      (MIC) method. The DNA cleavage activities of all the complexes were studied by
      agarose gel electrophoresis method. In addition, the free ligand along with its
      complexes has been studied for their antioxidant activity. 

PMID- 25371659
TI  - Axially Ligated Zirconium(IV) Tetraphenylporphyrin: Synthesis, Characterization,
      and Biological Activity.
AB  - A series of 5,10,15,20-tetraphenylporphinatozirconium(IV)
      acetylacetonatophenolates containing different phenols as axial ligands
      [Zr(TPP)(Y)(X)] (TPP = 5,10.15,20-tetraphenyl-21H, 23H-porphine; Y = acac; X =
      different phenolates) have been synthesized and characterized by various
      spectrochemical studies. The complexes were also screened for antimicrobial
      activities. Antifungal activity of some adducts has been carried out against the
      fungal strain Sclerotium rolfsii. Most of the complexes have shown good
      antibacterial activity. 

PMID- 25371660
TI  - Potentiometric and Blood Plasma Simulation Studies of Nickel(II) Complexes of
      Poly(amino)amido Pentadentate Ligands: Computer Aided Metal-Based Drug Design.
AB  - The thermodynamic equilibria of nickel(II) with N,N'-di(aminoethylene)-2,6
      pyridinedicarbonylamine (L1), Bis-(N,N-dimethylethyl)-2,6-pyridinedicarboxamide
      (L2), and N,N'-bis[2(2-pyridyl)-methyl]pyridine-2,6-dicarboxamide (L3) have been
      studied at 25 degrees C and an ionic strength of 0.15 mol dm(-3) by glass
      electrode potentiometry. The protonation and formation constants added to blood
      plasma model predict that Cu(II) competes effectively against Ni(II), Zn(II), and
      Ca(II) for these ligands in vivo. 

PMID- 25371661
TI  - Test-retest reliability and validity of a web-based food-frequency questionnaire
      for adolescents aged 13-14 to be used in the Norwegian Mother and Child Cohort
      Study (MoBa).
AB  - BACKGROUND: The assessment of food intake is challenging and prone to errors; it
      is therefore important to consider the reliability and validity of the assessment
      methods. OBJECTIVE: The aim of this study was to analyze the reproducibility and
      validity of a developed food-frequency questionnaire (FFQ) for use among
      adolescents. DESIGN: In total, 58 students (aged 13-14) from four different
      schools in the southern part of Norway participated in the reproducibility study
      of filling out the FFQ 4 weeks apart. In addition, 93 students participated in
      the relative validity study where the FFQ was compared to 2*24-hour dietary
      recalls, while 92 students participated in the absolute validity study where the
      intakes of fatty acids and vitamin D from the FFQ were compared to fatty acids
      and 25-hydroxy-vitamin D3 in whole blood. RESULTS: The median Spearman
      correlation coefficient for all nutrients in the test-retest reliability study
      was 0.57. The median Spearman correlation for all nutrients in the relative
      validity study was 0.26, while the correlations coefficients were low in the
      absolute validity study with n-3 fatty acid coefficients ranging from 0.05 to
      0.25, and absent for vitamin D (r=0.000). CONCLUSION: The test-retest
      reproducibility was considered good, the relative validity was considered poor to
      good, and the absolute validity was considered poor. However, the results are
      comparable to other studies among adolescents.

PMID- 25371662
TI  - PPAR Gamma Expression Levels during Development of Heart Failure in Patients with
      Coronary Artery Disease after Coronary Artery Bypass-Grafting.
AB  - Genetic research has elucidated molecular mechanisms of heart failure (HF).
      Peroxisome proliferator-activated receptors (PPARs) seem to be important in
      etiology of HF. The aim of study was to find the correlation between PPARgamma
      expression during development of HF in patients and coronary artery disease (CAD)
      after coronary artery bypass-grafting (CABG). Methods and Results. We followed up
      157 patients (mean age 63) with CAD without clinical, laboratory, or echo
      parameters of HF who underwent CABG. Clinical and laboratory status were assessed
      before CABG and at 1, 12, and 24 months. During CABG slices of aorta (Ao) and LV
      were collected for genetic research. HF was defined as LVEF <40% or NT-proBNP
      >400 pg/mL or 6MWT <400 m. Patients were divided into 2 groups: with and without
      HF. PPARgamma expression in Ao and LV was not increased in both groups at 2-year
      follow-up. Sensitivity of PPARgamma expression in Ao above 1.1075 in detection of
      HF was 20.5% (AUC 0.531, 95% CI 0.442-0.619). Positive predictive value (Ppv) was
      85.7%. Sensitivity and specificity of PPARgamma expression in the LV in detection
      of HF were 58% and 92.9%, respectively (AUC 0.540, 95% CI 0.452-0.626). Ppv was
      73.2%. Conclusion. PPARgamma expression in Ao and LV was comparable and should
      not be used as predictive factor for development of HF in patients with CAD after
      CABG. 

PMID- 25371663
TI  - The Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor Gamma
      Gene Modifies the Association of Physical Activity and Body Mass Changes in
      Polish Women.
AB  - Peroxisome proliferator-activated receptor gamma is a key regulator of
      adipogenesis, responsible for fatty acid storage and maintaining energy balance
      in the human body. Studies on the functional importance of the PPARG Pro12Ala
      polymorphic variants indicated that the observed alleles may influence body mass
      measurements; however, obtained results were inconsistent. We have decided to
      check if body mass changes observed in physically active participants will be
      modulated by the PPARG Pro12Ala genotype. The genotype distribution of the PPARG
      Pro12Ala allele was examined in a group of 201 Polish women measured for selected
      body mass variables before and after the completion of a 12-week training
      program. The results of our experiment suggest that PPARG genotype can modulate
      training-induced body mass measurements changes: after completion of the training
      program, Pro12/Pro12 homozygotes were characterised by a greater decrease of body
      fat mass measurements in comparison with 12Ala allele carriers. These results
      indicate that the PPARG 12Ala variant may impair the training-induced positive
      effects on body mass measurements; however, the detailed mechanism of such
      interaction remained unclear and observed correlation between PPARG genotype and
      body mass differential effects should be interpreted with caution. 

PMID- 25371664
TI  - The impact of chronic kidney disease and short-term treatment with rosiglitazone
      on plasma cell-free DNA levels.
AB  - Patients with chronic kidney disease (CKD) are at increased risk of
      cardiovascular disease. Circulating free nucleic acids, known as cell-free DNA
      (cfDNA), have been proposed as a novel biomarker of cardiovascular risk. The
      impact of renal impairment on cfDNA levels and whether cfDNA is associated with
      endothelial dysfunction and inflammation in CKD has not been systematically
      studied. We analysed cfDNA concentrations from patients with varying degrees of
      CKD. In addition, to determine whether there is a relationship between cfDNA,
      inflammation, and endothelial dysfunction in CKD, levels of proinflammatory
      cytokines and von Willebrand Factor (vWF) were measured in patients treated with
      the peroxisome proliferator-activated receptor gamma agonist rosiglitazone or
      placebo for 8 weeks. cfDNA levels were not increased with renal impairment or
      associated with the degree of renal dysfunction (P = 0.5). Treatment with
      rosiglitazone for 8 weeks, but not placebo, was more likely to lead to a
      reduction in cfDNA levels (P = 0.046); however, the absolute changes in cfDNA
      concentrations during treatment were not statistically significant (P > 0.05).
      cfDNA levels correlated with markers of endothelial dysfunction (hsCRP P =
      0.0497) and vWF (P = 0.0005). In conclusion, cell-free DNA levels are not
      influenced by renal impairment but do reflect endothelial dysfunction in patients
      with CKD. 

PMID- 25371665
TI  - Hypergraph-based recognition memory model for lifelong experience.
AB  - Cognitive agents are expected to interact with and adapt to a nonstationary
      dynamic environment. As an initial process of decision making in a real-world
      agent interaction, familiarity judgment leads the following processes for
      intelligence. Familiarity judgment includes knowing previously encoded data as
      well as completing original patterns from partial information, which are
      fundamental functions of recognition memory. Although previous computational
      memory models have attempted to reflect human behavioral properties on the
      recognition memory, they have been focused on static conditions without
      considering temporal changes in terms of lifelong learning. To provide temporal
      adaptability to an agent, in this paper, we suggest a computational model for
      recognition memory that enables lifelong learning. The proposed model is based on
      a hypergraph structure, and thus it allows a high-order relationship between
      contextual nodes and enables incremental learning. Through a simulated
      experiment, we investigate the optimal conditions of the memory model and
      validate the consistency of memory performance for lifelong learning. 

PMID- 25371666
TI  - A new optimized GA-RBF neural network algorithm.
AB  - When confronting the complex problems, radial basis function (RBF) neural network
      has the advantages of adaptive and self-learning ability, but it is difficult to
      determine the number of hidden layer neurons, and the weights learning ability
      from hidden layer to the output layer is low; these deficiencies easily lead to
      decreasing learning ability and recognition precision. Aiming at this problem, we
      propose a new optimized RBF neural network algorithm based on genetic algorithm
      (GA-RBF algorithm), which uses genetic algorithm to optimize the weights and
      structure of RBF neural network; it chooses new ways of hybrid encoding and
      optimizing simultaneously. Using the binary encoding encodes the number of the
      hidden layer's neurons and using real encoding encodes the connection weights.
      Hidden layer neurons number and connection weights are optimized simultaneously
      in the new algorithm. However, the connection weights optimization is not
      complete; we need to use least mean square (LMS) algorithm for further leaning,
      and finally get a new algorithm model. Using two UCI standard data sets to test
      the new algorithm, the results show that the new algorithm improves the operating
      efficiency in dealing with complex problems and also improves the recognition
      precision, which proves that the new algorithm is valid. 

PMID- 25371667
TI  - Superpulsed CO 2 Laser with Intraoperative Pathologic Assessment for Treatment of
      Periorbital Basal Cell Carcinoma Involving Eyelash Line.
AB  - Background. Periorbital basal cell carcinoma (BCC) is considered a high risk case
      because it is associated with high rate of recurrence and complication.
      Superpulsed CO2 laser with intraoperative pathologic assessment could be an
      alternative and appropriate treatment for periocular lesions where Mohs
      micrographic surgery is not available. Objective. To evaluate the efficacy of
      superpulsed CO2 laser therapy with intraoperative pathologic assessment on
      periocular BCC involving eyelash line. Method. This follow-up study was performed
      on 20 patients with a total of 21 BCC lesions that were pathologically
      documented. Firstly, debulkation of tumoral mass was done by curettage. Then,
      irradiation and intraoperative pathologic evaluation were done by concurrent CO2
      laser. The patients were followed up for a period of 36 months. Results. Out of
      21 lesions, the nodular type accounted for 15 (71.4%) lesions, and 12 (57.1%)
      lesions were seen in the lower lid as the most common clinical type and site
      involvement. Twenty BCC lesions (95.2%) were treated after one session. Damage to
      eyelash was seen in 2 (10%) patients, but ectropion and other complications were
      not seen in any patient. Conclusion. Treatment with superpulsed CO2 laser and
      intraoperative pathologic evaluation for periorbital BCC lesions much close to
      conjunctiva could be an effective method with minimal complications without major
      danger of recurrence. This modality can be used with care in the inner canthus
      and high risk pathologic lesions. 

PMID- 25371668
TI  - A school-based study of irritable bowel syndrome in medical students in beijing,
      china: prevalence and some related factors.
AB  - Purpose. To investigate the prevalence and some related factors about irritable
      bowel syndrome (IBS) in medical students. Methods. A cross-sectional study was
      carried out from February 2014 to Jun 2014 in Beijing University of Chinese
      Medicine, Beijing, China. All participants were asked to completed self
      administered questionnaires. Results. Seven hundred and sixty-seven medical
      students (23.26 +/- 2.88 years, 25.6% males) completed the survey. The prevalence
      of IBS was 33.3%, with a high prevalence in women (36.1%). Among the IBS
      patients, 112 cases were IBS-M (43.9%) and 77.6% had moderately severe IBS. There
      were no statistical differences between control group and IBS patients in anxiety
      and depression scores (P > 0.05). The total score of Pittsburgh sleep quality
      index (PSQI) was significantly higher for medical students with IBS and 35.5% of
      IBS patients had severe sleep disorder; the scores of child trauma questionnaire
      (CTQ) and student-life stress inventory (SLSI) were also higher in IBS patients.
      Sex and sleep disorder were independently associated with IBS (OR, 1.914, 95%CI,
      1.281-2.860; OR, 1.143, 95%CI, 1.074-1.216). Conclusion. Our study has many
      valuable findings and they may provide valuable suggestions for the necessary
      intervention and treatment measures towards medical students. 

PMID- 25371669
TI  - COX-2 Inhibitors and Gastric Cancer.
AB  - The evidence that cyclooxygenase-2 (COX-2) is upregulated and plays an important
      role in carcinogenesis of gastric cancer has triggered the topic of COX-2
      inhibitors as chemopreventive agents for gastric cancer. Studies find that COX-2
      inhibitors are associated not only with chemoprophylactic effects, but also with
      chemotherapeutic potentials in gastric cancer. Both COX-dependent and COX
      independent pathways have a role in the anticancer efficiency of COX-2
      inhibitors. However, enthusiasm is thwarted by the potential toxicity, that is,
      gastrointestinal toxicity of nonselective COX-2 inhibitors and cardiovascular
      risk of selective COX-2 inhibitors. Therefore, more studies are needed to develop
      new targeted antitumor agents (such as prostaglandin E receptor antagonist) and
      to define fundamental questions such as optimal treatment regimens, integration
      of cotherapy, and careful selection of candidates. 

PMID- 25371670
TI  - Endosonographic features of histologically proven gastric ectopic pancreas.
AB  - Gastric ectopic pancreas is an uncommon developmental anomaly and its
      histological diagnosis is usually difficult by using a conventional biopsy
      forceps. In the literature, most cases of gastric ectopic pancreas were usually
      diagnosed by gross pattern during endoscopic examination or features of
      endoscopic ultrasound. In contrast, this disease was seldom diagnosed by
      histology in clinical practice. Although the typical endoscopic ultrasonographic
      features of ectopic pancreas include heterogeneous echogenicity, indistinct
      borders, and a location within 2 or more layers, it can also exhibit hypoechoic
      homogeneous echogenicity and a distinct border within the fourth sonographic
      layer (muscularis propria) similar to the endoscopic ultrasonographic features of
      gastrointestinal stromal tumors. In our study, we found that 53% of gastric
      ectopic pancreas originated within the fourth sonographic layer, demonstrating
      hypoechoic, homogeneous echogenicity, and distinct borders. Therefore,
      recognizing endoscopic ultrasonographic features, combining with deep biopsy,
      endoscopic ultrasound-guided fine needle aspiration/core needle biopsy can
      prevent conducting unnecessary resection. Surgical resection is the mainstay
      treatment for symptomatic gastric ectopic pancreas, but endoscopic resection
      using endoscopic mucosal resection or endoscopic submucosal dissection technique
      provides an alternative method of removing superficial-type and deep-type gastric
      ectopic pancreas. 

PMID- 25371671
TI  - Assessment of gastric phenotypes using magnifying narrow-band imaging for
      differentiation of gastric carcinomas from adenomas.
AB  - Background. Conventional white-light endoscopy and forceps biopsy are
      insufficient for definitive diagnosis of gastric adenoma. Immunohistochemical
      studies have reported an obvious phenotypic difference between adenomas and
      carcinomas. We investigated the utility of narrow-band imaging with magnifying
      endoscopy (NBI-ME) for mucin phenotypic assessment to differentiate carcinomas
      from adenomas. Methods. NBI-ME findings were classified into A, B, and AB types,
      which revealed papillary, tubular pits and groove microstructures, respectively.
      To investigate A-B classifications retrospectively, 137 patients (155 lesions)
      that were diagnosed pretherapeutically with adenoma or borderline lesions by
      biopsy were enrolled. The mucin phenotype was analyzed immunohistochemically in
      the first 60 lesions. Results. After endoscopic submucosal dissection, A type and
      AB type lesions were determined histologically as carcinoma (81/82, 99%). B type
      lesions were adenoma (29/73, 40%) and carcinoma (44/73, 60%). A or AB type
      correlated to histological carcinomas (sensitivity 65%, specificity 97%, and
      accuracy 71%). Mucin phenotypes were gastric or gastrointestinal in A type and AB
      type carcinomas (31/37, 84%) and intestinal in B type adenomas and carcinomas
      (21/23, 91%). Conclusions. NBI-ME has the advantage of the assessment of mucin
      phenotypes in gastric carcinomas and adenomas. The proposed A-B classification is
      useful, especially for differentiation of gastric or gastrointestinal carcinomas
      from adenomas. 

PMID- 25371672
TI  - Flt3/Flt3L Participates in the Process of Regulating Dendritic Cells and
      Regulatory T Cells in DSS-Induced Colitis.
AB  - The immunoregulation between dendritic cells (DCs) and regulatory T cells (T
      regs) plays an important role in the pathogenesis of ulcerative colitis (UC).
      Recent research showed that Fms-like tyrosine kinase 3 (Flt3) and Flt3 ligand
      (Flt3L) were involved in the process of DCs regulating T-regs. The DSS-induced
      colitis model is widely used because of its simplicity and many similarities with
      human UC. In this study, we observe the disease activity index (DAI) and
      histological scoring, detect the amounts of DCs and T-regs and expression of
      Flt3/Flt3L, and investigate Flt3/Flt3L participating in the process of DCs
      regulating T-regs in DSS-induced colitis. Our findings suggest that the reduction
      of Flt3 and Flt3L expression may possibly induce colonic immunoregulatory
      imbalance between CD103(+)MHCII(+)DCs and CD4(+)CD25(+)FoxP3(+)T-regs in DSS
      induced colitis. Flt3/Flt3L participates in the process of regulating DCS and T
      regs in the pathogenesis of UC, at least, in the acute stage of this disease. 

PMID- 25371673
TI  - S100A8 and S100A9 Positive Cells in Colorectal Carcinoma: Clinicopathological
      Analysis.
AB  - Introduction. In colorectal carcinoma, tumoral tissues infiltrate with various
      immune/inflammatory cells along their invasive margins and the increased
      S100A8/A9 expression in these immune cells infiltrating the tumor has recently
      been demonstrated. We examined S100A8/A9 as a potential therapeutic target in the
      treatment of colorectal carcinoma. Materials and Methods. The current study
      included a sample of 80 patients diagnosed with CRC (30 cases with distant
      metastasis, 30 cases with lymph node metastasis, and 20 cases with no
      metastasis). Peritumoral and intratumoral S100A8 and S100A9 expressing
      inflammatory cells were counted in primary tumors and their metastasis and
      correlated with clinicopathological parameters. Results. The peritumoral and
      intratumoral S100A8/A9 positive cells showed no correlation with age, gender, or
      depth of tumor invasion. However higher counts of peritumoral and intratumoral
      S100A8/A9 positive cells were associated with larger tumor size, higher grade,
      and the presence of metastasis (P < 0.05). Conclusion. Our study also found
      significantly higher number of S100A8/A9 positive cells in the tumor
      microenvironment among patients with large tumor size, high grade, and metastatic
      disease. Moreover, in our study, we observed that the expression in the tumor
      metastasis appeared similar to that of primary tumor. 

PMID- 25371674
TI  - Prevalence and Determinants of Fall-Related Injuries among Older Adults in
      Ecuador.
AB  - Objectives. To estimate the prevalence and determinants of fall-related injuries
      in the previous year among adults aged 60 years or older in Ecuador. Methods. The
      prevalence of fall-related injuries was estimated using cross-sectional data from
      the first national survey of Health, Wellbeing, and Aging study. Logistic
      regression models were used to examine the associations between participants'
      demographic characteristics and fall-related injuries. Results. Of 5,227
      participants with a mean age of 72.6 years, 11.4% (95% CI, 10.3%-12.7%) reported
      a fall-related injury in Ecuador, representing an estimated 136,000 adults aged
      60 years or older. Fall-related injuries were more frequently reported among
      older adults residing in the most urbanized and populated provinces of the
      country. After controlling for potential confounders, self-reported race as
      Indigenous (OR 2.2; 95% CI, 2.11-2.31), drinking alcohol regularly (OR 2.54; 95%
      CI, 2.46-2.63), subjects with greater number of comorbid conditions (OR 2.03; 95%
      CI, 1.97-2.08), and urinary incontinence (OR 1.83; 95% CI, 1.79-1.87) were
      factors independently associated with increased odds of sustaining fall-related
      injuries. Conclusions. Fall-related injuries represent a considerable burden for
      older adults in Ecuador. The present findings may assist public health
      authorities to implement fall prevention programs among subjects at higher risk
      for this type of injury. 

PMID- 25371675
TI  - A Hybrid Method for Endocardial Contour Extraction of Right Ventricle in 4-Slices
      from 3D Echocardiography Dataset.
AB  - This paper presents a hybrid method to extract endocardial contour of the right
      ventricular (RV) in 4-slices from 3D echocardiography dataset. The overall
      framework comprises four processing phases. In Phase I, the region of interest
      (ROI) is identified by estimating the cavity boundary. Speckle noise reduction
      and contrast enhancement were implemented in Phase II as preprocessing tasks. In
      Phase III, the RV cavity region was segmented by generating intensity threshold
      which was used for once for all frames. Finally, Phase IV is proposed to extract
      the RV endocardial contour in a complete cardiac cycle using a combination of
      shape-based contour detection and improved radial search algorithm. The proposed
      method was applied to 16 datasets of 3D echocardiography encompassing the RV in
      long-axis view. The accuracy of experimental results obtained by the proposed
      method was evaluated qualitatively and quantitatively. It has been done by
      comparing the segmentation results of RV cavity based on endocardial contour
      extraction with the ground truth. The comparative analysis results show that the
      proposed method performs efficiently in all datasets with overall performance of
      95% and the root mean square distances (RMSD) measure in terms of mean +/- SD was
      found to be 2.21 +/- 0.35 mm for RV endocardial contours. 

PMID- 25371676
TI  - The Optimal Approach for Laparoscopic Adrenalectomy through Mono Port regarding
      Left or Right Sides: A Comparative Study.
AB  - Introduction. Several studies have shown the feasibility and safety of both
      transperitoneal and posterior retroperitoneal approaches for single incision
      laparoscopic adrenalectomy, but none have compared the outcomes according to the
      left- or right-sided location of the adrenal glands. Materials and Methods. From
      2009 to 2013, 89 patients who received LAMP (laparoscopic adrenalectomy through
      mono port) were analyzed. The surgical outcomes attained using the
      transperitoneal approach (TPA) and posterior retroperitoneal approach (PRA) were
      analyzed and compared. Results and Discussion. On the right side, no significant
      differences were found between the LAMP-TPA and LAMP-PRA groups in terms of
      patient characteristics and clinicopathological data. However, outcomes differed
      in which LAMP-PRA group had a statistically significant shorter mean operative
      time (84.13 +/- 41.47 min versus 116.84 +/- 33.17 min; P = 0.038), time of first
      oral intake (1.00 +/- 0.00 days versus 1.21 +/- 0.42 days; P = 0.042), and length
      of hospitalization (2.17 +/- 0.389 days versus 3.68 +/- 1.38 days; P <= 0.001),
      whereas in left-sided adrenalectomies LAMP-TPA had a statistically significant
      shorter mean operative time (83.85 +/- 27.72 min versus 110.95 +/- 29.31 min; P =
      0.002). Conclusions. We report that LAMP-PRA is more appropriate for right-sided
      laparoscopic adrenalectomies due to anatomical characteristics and better
      surgical outcomes. For left-sided laparoscopic adrenalectomies, however, we
      propose LAMP-TPA as a more suitable method. 

PMID- 25371677
TI  - Pain Perception and Anxiety Levels during Menstrual Cycle Associated with
      Periodontal Therapy.
AB  - Objectives. To compare the pain perception and anxiety levels of female patients
      undergoing scaling and root planing during menstrual (perimenstrual) period with
      those observed during postmenstrual period. Materials and Methods. This was a
      single blind study, with a split-mouth design. Forty-four women with chronic
      periodontitis with regular menstrual cycles were subjected to complete Corah's
      Dental Anxiety Scale (DAS) during their first debridement visit. Patients were
      randomly selected to undergo their first debridement visit during either their
      menstrual or postmenstrual period. Scaling was performed under local anesthesia
      in bilateral quadrants of patients during the periods. Visual Analogue Scale
      (VAS) was used to score pain levels for each quadrant after performing scaling
      and root planing. Results. Increase in pain perception among females during their
      menstrual or perimenstrual period was significantly greater than their
      postmenstrual period (P < 0.05). It is observed that women whose first
      appointment was given in perimenstrual period had more pain (VAS) (P = 0.0000)
      when compared to those women whose first appointment was given in postmenstrual
      period. Conclusion. Females in their menstrual period demonstrated higher pain
      responses and high anxiety levels to supra- and subgingival debridement. This
      increase in the pain levels of women during their menstrual period was
      statistically significant. If the appointments are given in postmenstrual period,
      women feel less pain. 

PMID- 25371679
TI  - Trial of Zolpidem, Eszopiclone, and Other GABA Agonists in a Patient with
      Progressive Supranuclear Palsy.
AB  - Progressive supranuclear palsy (PSP) is a progressive, debilitating
      neurodegenerative disease of the Parkinson-plus family of syndromes.
      Unfortunately, there are no pharmacologic treatments for this condition, as most
      sufferers of the classic variant respond poorly to Parkinson medications such as
      levodopa. Zolpidem, a gamma aminobutyric acid (GABA) agonist specific to the
      alpha-1 receptor subtype, has been reported to show improvements in symptoms of
      PSP patients, including motor dysfunction, dysarthria, and ocular disturbances.
      We observed a 73-year-old woman with a six-year history of PSP, who, upon
      administration of a single 12.5 mg dose of sustained-release zolpidem, exhibited
      marked enhancements in speech, facial expressions, and fine motor skills for five
      hours. These results were reproduced upon subsequent clinic visits. In an effort
      to find a sustainable medication that maximized these beneficial effects while
      minimizing side effects and addressing some of her comorbid neuropsychological
      conditions, a trial of five other GABA receptor agonists was performed with the
      patient's consent, while she and her caregivers were blinded to the specific
      medications. She and her caretakers subsequently reported improvements,
      especially visual, while on eszopiclone, and, to a lesser degree, temazepam and
      flurazepam. 

PMID- 25371678
TI  - In Vitro Evaluation of the Antimicrobial Efficacy of Four Endodontic Biomaterials
      against Enterococcus faecalis, Candida albicans, and Staphylococcus aureus.
AB  - Root canal sealers that possess good antimicrobial property can prevent residual
      and recurrent infection and contribute to successful endodontic therapy. This
      study evaluated the antimicrobial activity of four endodontic sealers, AH Plus,
      Tubliseal EWT, EndoRez, and iRoot SP, against three different microorganisms, E.
      faecalis, C. albicans, and S. aureus, by direct contact test. 10 MUL microbial
      suspensions were allowed to directly contact the four endodontic sealers for 1 hr
      at 37 degrees C. Subsequently microbial growth was measured
      spectrophotometrically every 30 min for 18 hours. The microbial suspensions were
      simultaneously tested to determine the antimicrobial effect of components which
      are capable of diffusing into the medium. The results revealed that AH Plus and
      iRootSP had significantly higher antimicrobial activity against E. faecalis. AH
      Plus and Tubliseal EWT showed significantly higher antimicrobial activity against
      C. albicans and S. aureus compared to iRoot SP and EndoRez. EndoRez showed the
      least antimicrobial activity against all the three microorganisms. Inhibition of
      microbial growth is related to the direct contact of microorganisms with the
      sealers. In conclusion AH Plus had significantly higher antimicrobial activity
      against E. faecalis, C. albicans, and S. aureus. 

PMID- 25371680
TI  - Serological findings in a child with paroxysmal cold haemoglobinuria.
AB  - PCH is a rare autoimmune hemolytic anemia (AIHA) but is one of the most common
      causes of AIAH in children. For the diagnosis, it is important to perform the
      appropriate methods of serological investigation and show the typical biphasic
      reaction. This is a case report of a child who presented with features of
      haemolysis and was diagnosed with PCH of this way. 

PMID- 25371681
TI  - Adult ocular toxocariasis mimicking ciliary body malignancy.
AB  - Purpose. To discuss an unusual presentation of ocular toxocariasis. Methods. Case
      report. Results. A 40-year-old woman presented with decreased vision in the left
      eye with a long history of recurrent red eye from uveitis. Eosinophilia and
      positive ELISA titers for Toxocara canis favored the diagnosis of ocular
      toxocariasis. Over 3 months, an anterior scleral mass had a rapid growth raising
      the possibility of medulloepithelioma, which rarely can mimic uveitic syndromes.
      Surgical plan changed from local excision to enucleation. Histopathology
      demonstrated a large homogeneous mass of chronic inflammatory cells with
      inflammation of the overlying thinned out sclera, medial rectus insertion, and
      limbal cornea. The triad of peripheral granuloma, eosinophilia, and positive
      blood serology established the diagnosis of ocular toxocariasis. Conclusions.
      Ocular toxocariasis can mimic ocular malignancy such as medulloepithelioma in
      adults and rarely presents as an anterior scleral mass. 

PMID- 25371682
TI  - Bill C-442: Shining the limelight on the Lyme-like?

PMID- 25371683
TI  - Antimicrobial stewardship in daily practice: Managing an important resource.
AB  - Antimicrobial stewardship is a recent concept that embodies the practical,
      judicious use of antimicrobials to decrease adverse outcomes from antimicrobials
      while optimizing the treatment of bacterial infections to reduce the emergence of
      resistant pathogens. The objectives of the present statement are to illustrate
      the principles of antimicrobial stewardship and to offer practical examples of
      how to make antimicrobial stewardship part of everyday hospital and outpatient
      practice. Vital components of antimicrobial stewardship include appropriate
      testing to diagnose whether infections are viral or bacterial, and using clinical
      follow-up rather than antibiotics in cases in which the child is not very ill and
      uncertainty exists. Other specific, important actions include questioning whether
      positive urine cultures are contaminated when there is no evidence of pyuria or
      inflammatory changes, and obtaining a chest radiograph to support a diagnosis of
      bacterial pneumonia. Optimizing the choice and dosage of antimicrobials also
      reduces the probability of clinical failures and subsequent courses of
      antimicrobials. A list of common clinical scenarios to promote stewardship is
      included. 

PMID- 25371684
TI  - A 39-year-old female immigrant with chronic diarrhea.

PMID- 25371686
TI  - An atypical cause of atypical chest pain.
AB  - The present report describes a case involving a 57-year-old HIV-positive man who
      presented with acute retrosternal chest pain accompanied by 24 h of fever. Septic
      arthritis of the manubriosternal joint was diagnosed based on magnetic resonance
      imaging findings in addition to Staphylococcus aureus bacteremia. To the authors'
      knowledge, the present case is only the 12th reported case of manubriosternal
      septic arthritis, and the first in an HIV-positive patient. Early diagnosis and
      treatment can circumvent the need for surgical intervention. Based on the present
      case report and review of the literature, the authors summarize the epidemiology,
      appropriate imaging and suggestions for antibiotic therapy for this rare
      presentation. 

PMID- 25371685
TI  - Bacterial meningitis in the absence of cerebrospinal fluid pleocytosis: A case
      report and review of the literature.
AB  - Elevation of cerebrospinal fluid (CSF) cell count is a key sign in the diagnosis
      of bacterial meningitis. However, there have been reports of bacterial meningitis
      with no abnormalities in initial CSF testing. This type of presentation is
      extremely rare in adult patients. Here, a case involving an 83-year-old woman who
      was later diagnosed with bacterial meningitis caused by Neisseria meningitidis is
      described, in whom CSF at initial and second lumbar puncture did not show
      elevation of cell counts. Twenty-six non-neutropenic adult cases of bacterial
      meningitis in the absence of CSF pleocytosis were reviewed. The frequent
      causative organisms were Streptococcus pneumoniae and N meningitidis. Nineteen
      cases had bacteremia and seven died. The authors conclude that normal CSF at
      lumbar puncture at an early stage cannot rule out bacterial meningitis.
      Therefore, repeat CSF analysis should be considered, and antimicrobial therapy
      must be started immediately if there are any signs of sepsis or meningitis. 

PMID- 25371687
TI  - Dokdonella koreensis bacteremia: A case report and review of the literature.
AB  - Dokdonella koreensis is a non-spore-forming, aerobic, Gram-negative bacillus that
      was initially isolated from soil. The pathogenicity of this organism in humans
      remains unclear. The authors report a case of successfully treated D koreensis
      bacteremia in a patient with a hematological malignancy who presented with a
      fever and palmar-plantar erythrodysesthesia. 

PMID- 25371688
TI  - Nutritional supplementation with the mushroom Agaricus sylvaticus reduces
      oxidative stress in children with HIV.
AB  - BACKGROUND: The involvement of free radicals and oxidative stress in HIV
      infection has been extensively studied, and the benefits of antioxidant
      supplementation in animal studies have been demonstrated. However, few studies
      have demonstrated a benefit in clinical studies. OBJECTIVE: To verify the effects
      of dietary supplementation with Agaricus sylvaticus, a mushroom rich in
      antioxidants, on the oxidative profile of children born with HIV undergoing
      antiretroviral therapy. DESIGN: The sample included 24 children (both boys and
      girls) between two and eight years of age, of whom 10 were HIV positive and
      received supplementation with Agaricus sylvaticus for a three-month period, and
      14 were HIV negative and received no supplementation. At the beginning and
      conclusion of the study, thiobarbituric acid-reactive substances (TBARS), nitrite
      and nitrate (NN), Trolox equivalent antioxidant capacity, and the antioxidant
      capacity of inhibition of diphenyl-picrilhidrazil (DPPH) free radicals were
      analyzed. RESULTS: Before supplementation, significantly higher values of TBARS
      and NN, but decreased values of DPPH, were observed in infected subjects when
      compared with HIV-negative subjects. After supplementation, a reduction of TBARS
      and NN values and an increase in DPPH and Trolox equivalent antioxidant capacity
      values were observed in HIV-positive subjects. CONCLUSIONS: The results of the
      present study suggest the involvement of oxidative stress in HIV infection, with
      the participation of NN synthesis. Additionally, supplementation reversed
      oxidative alterations and improved antioxidant defense in infected individuals,
      and may become a complementary strategy in the treatment of these patients.

PMID- 25371689
TI  - Hospital ward design and prevention of hospital-acquired infections: A
      prospective clinical trial.
AB  - BACKGROUND: Renovation of a general medical ward provided an opportunity to study
      health care facility design as a factor for preventing hospital-acquired
      infections. OBJECTIVE: To determine whether a hospital ward designed with
      predominantly single rooms was associated with lower event rates of hospital
      acquired infection and colonization. METHODS: A prospective controlled trial with
      patient allocation incorporating randomness was designed with outcomes on
      multiple 'historic design' wards (mainly four-bed rooms with shared bathrooms)
      compared with outcomes on a newly renovated 'new design' ward (predominantly
      single rooms with private bathrooms). RESULTS: Using Poisson regression analysis
      and adjusting for time at risk, there were no differences (P=0.18) in the primary
      outcome (2.96 versus 1.85 events/1000 patient-days, respectively). After
      adjustment for age, sex, Charlson score, admitted from care facility, previous
      hospitalization within six months, isolation requirement and the duration on
      antibiotics, the incidence rate ratio was 1.44 (95% CI 0.71 to 2.94) for the new
      design versus the historic design wards. A restricted analysis on the numbers of
      events occurring in single-bed versus multibed wings within the new design ward
      revealed an event incidence density of 1.89 versus 3.47 events/1000 patient-days,
      respectively (P=0.18), and an incidence rate ratio of 0.54 (95% CI 0.15 to 1.30).
      CONCLUSIONS: No difference in the incidence density of hospital-acquired
      infections or colonizations was observed for medical patients admitted to a new
      design ward versus historic design wards. A restricted analysis of events
      occurring in single-bed versus multibed wings suggests that ward design warrants
      further study.

PMID- 25371690
TI  - Serum voriconazole level variability in patients with hematological malignancies
      receiving voriconazole therapy.
AB  - INTRODUCTION: Voriconazole plasma concentrations have been correlated with oral
      dosing in healthy subjects, but have been poorly characterized in ill patients
      with hematological malignancies receiving intensive chemotherapy. METHODS: The
      relationship between orally administered voriconazole, plasma concentrations and
      liver toxicity was examined in a cohort of 69 primarily acute leukemia patients
      undergoing intensive chemotherapy. RESULTS: Oral administration of voriconazole
      was associated with significant interpatient variability, with voriconazole
      steady-state concentrations ranging from 0 MUg/mL to 16.6 MUg/mL. Approximately
      20% of patients achieved steady-state concentrations <1 MUg/mL. When adjusted for
      weight, patients receiving higher voriconazole doses tended toward higher plasma
      concentrations; however, there was no significant relationship between the plasma
      concentration and genotype, age, sex or use of concomitant proton pump
      inhibitors. Voriconazole concentrations were correlated with higher serum
      alkaline phosphatase levels at day 6 to 8, and with higher bilirubin and
      aspartate aminotransferase levels at day 14 to 16, but not with other liver
      enzyme levels. CONCLUSION: In ill patients with acute leukemia and related
      disorders undergoing treatment with oral voriconazole, there is a poor
      correlation between the voriconazole dose and plasma concentrations, and many
      patients achieve levels that are considered to be subtherapeutic. The findings
      support the routine use of therapeutic drug monitoring in these patients.

PMID- 25371691
TI  - Correlates of illness severity in infectious mononucleosis.
AB  - INTRODUCTION: Understanding the spectrum and frequencies of Epstein-Barr virus
      (EBV) complications and markers of illness severity in immunocompetent patients
      with primary EBV infection will inform management of patients with EBV-related
      illnesses. OBJECTIVES: To determine the clinical and laboratory correlates of
      illness severity among infants, children and youth with infectious mononucleosis
      (IM). METHODS: Study subjects with confirmed IM were prospectively enrolled.
      Illness severity was assessed at baseline and at six weeks using a scoring tool.
      Peripheral blood viral loads served as a measure of viral burden. RESULTS: Among
      32 children and young adults with IM, the median age was 16 years (range two to
      24 years). The predominant clinical findings were lymphadenopathy (23 of 32
      [72%]), pharyngitis (16 of 32 [50%]), fever (nine of 32 [28%]) and splenomegaly
      (six of 32 [19%]). With respect to symptoms or signs that persisted to at least
      six weeks after illness onset, the predominant complaint was lymphadenopathy in
      35% of subjects available for reassessment. Deranged liver function tests were
      present at presentation in up to 44% of subjects. Patients with the highest viral
      loads at presentation had significantly higher illness severity scores associated
      with fatigue (P=0.02). Other than the scores associated with fatigue, viral load
      values were not significantly correlated with the illness severity scores at
      baseline and at six weeks. CONCLUSION: In IM, viral loads are not necessarily
      correlated with illness severity, with the exception of fatigue. EBV-related
      hepatitis is common in IM, confirming the status of this virus as a relatively
      common cause of transient hepatitis in children and youth. This entity is not
      necessarily a marker of disease severity.

PMID- 25371692
TI  - Factors associated with noncompletion of latent tuberculosis infection treatment
      in an inner-city population in Edmonton, Alberta.
AB  - A limited number of studies have been published that examine treatment completion
      rates and interventions used to increase treatment completion within an inner
      city population. The purpose of the present study was to determine the rate of
      latent tuberculosis infection (LTBI) treatment completion in an inner-city
      population in Edmonton, Alberta, and to identify factors that correlated with
      treatment completion. A retrospective chart review was conducted involving
      patients who started LTBI treatment between January 1, 2005 and December 31, 2010
      in Edmonton's inner city. A total of 77 patients started treatment and 57 (74%)
      patients completed LTBI treatment. Homelessness was the only variable that was
      significantly associated with incomplete treatment (OR 8.0 [95% CI 1.4 to 45.6])
      and it remained significant when controlling for drug use (adjusted OR 6.5 [95%
      CI 1.1 to 38.8]). While the present study demonstrated treatment completion rates
      comparable with or better than those described in the general population, it
      highlighted the need for continued emphasis on interventions aimed at improving
      outcomes within homeless populations. 

PMID- 25371693
TI  - Effects of breakpoint changes on carbapenem susceptibility rates of
      Enterobacteriaceae: Results from the SENTRY Antimicrobial Surveillance Program,
      United States, 2008 to 2012.
AB  - In the absence of clinical resistance, breakpoints for many antimicrobial agents
      are often set high. Clinical failures following use of the agents over time
      requires re-evaluation of breakpoints. This is based on patient response,
      pharmacokinetic/pharmacodynamic information and in vitro minimal inhibitory
      concentration data. Data from the SENTRY Antimicrobial Surveillance Program has
      shown that Clinical and Laboratory Standards Institute breakpoint changes for
      carbapenems that occurred between 2008 and 2012 in North America have resulted in
      decreased levels of susceptibility for some species. In particular, reduced
      susceptibility to imipenem was observed for Proteus mirabilis (35%) and
      Morganella morganii (80%). Minor decreases in susceptibility were also noted for
      Enterobacter species with ertapenem (5%) and imipenem (4.3%), and Serratia
      species with imipenem (6.4%). No significant decreases in susceptibility were
      observed for meropenem following the breakpoint changes. There were no earlier
      breakpoints established for doripenem. Very few of these Enterobacteriaceae
      produce carbapenamase enzymes; therefore, the clinical significance of these
      changes has not yet been clearly determined. In conclusion, ongoing surveillance
      studies with in vitro minimum inhibitory concentration data are essential in
      predicting the need for breakpoint changes and in identifying the impact of such
      changes on the percent susceptibility of different species. 

PMID- 25371694
TI  - Bacteremia caused by Eggerthella lenta in an elderly man with a gastrointestinal
      malignancy: A case report.
AB  - Eggerthella lenta is an anaerobic, Gram-positive bacillus commonly found in the
      human digestive tract. Occasionally, it can cause life-threatening infections.
      Bacteremia due to this organism is always clinically significant and is
      associated with gastrointestinal diseases and states of immune suppression. The
      authors report a case involving an elderly man with a newly diagnosed
      gastrointestinal malignancy who developed bacteremia caused by E lenta, treated
      successfully using empirical therapy with vancomycin and piperacillin-tazobactam,
      followed by directed therapy with metronidazole once the identity and antibiotic
      susceptibility of the organism was established. The present case reinforces the
      connection between E lenta bacteremia with gastrointestinal malignancy and
      highlights the importance of searching for a source of bacteremia due to this
      organism. 

PMID- 25371695
TI  - Evaluation of Wound Closure Activity of Nigella sativa, Melastoma malabathricum,
      Pluchea indica, and Piper sarmentosum Extracts on Scratched Monolayer of Human
      Gingival Fibroblasts.
AB  - Nigella sativa, Melastoma malabathricum, Pluchea indica, and Piper sarmentosum
      are common Asian traditional medicines to treat minor wounds. This study aimed to
      investigate the in vitro wound healing properties of aqueous extracts of these
      plants using human gingival fibroblast (HGF) monolayer as study model. DPPH
      scavenging activity of the extracts was evaluated and effect on HGF proliferation
      was determined. Their effect on HGF's function to synthesize collagen was
      indicated by the level of hydroxyproline produced and effect on wound healing
      activity was assessed using an in vitro scratch assay. The influence of the
      extracts on expression of bFGF and TGF-beta was also determined. Results revealed
      all four extracts to exhibit low free radical scavenging activity. The extract
      from N. sativa (NSSE) compared to the others showed favourable enhancement of HGF
      proliferation with EC50 of 22.67 +/- 3.06 ug/mL (P < 0.05) with accelerated wound
      closure activity despite its nonsignificant effect on collagen synthesis. In
      addition to the elevated level of bFGF by up to 15% at 100 ug/mL of NSSE, a
      slightly better effect was observed on the expression of TGF-beta. NSSE thus
      showed that promising wound healing properties and data obtained may contribute
      towards validation of its traditional use for the healing of oral wounds. 

PMID- 25371696
TI  - Coadministration of Pinellia ternata Can Significantly Reduce Aconitum
      carmichaelii to Inhibit CYP3A Activity in Rats.
AB  - Chuanwu (CW), the mother root of Aconitum carmichaelii Debx., is a traditional
      Chinese medicine (TCM) for treating traumatic injuries, rheumatoid arthritis, and
      tumors. CW coadministered with banxia (BX), the root of Pinellia ternata, is also
      widely prescribed in clinical practice. However, the mechanism of this
      combination is yet deciphered. Current study aimed to investigate the effects of
      CW, including raw chuanwu (RCW) and processed chuanwu (PCW) alone, as well as CW
      coadministered with BX on CYP3A activity. Buspirone (BP) and testosterone (Tes)
      were used as specific probe substrates in vivo and ex vivo, respectively. CYP3A
      activity was determined by the metabolites formation ratios from the substrates.
      Compared with those in the control group, the metabolites formation ratios
      significantly decreased in the RCW and PCW alone groups, accompanied by a marked
      decrease in CYP3A protein and mRNA levels. However, there was a significant
      increase in those ratios in the RCW-BX and PCW-BX groups compared to the RCW and
      PCW alone groups. The results indicated that both RCW and PCW can inhibit CYP3A
      activity in rats because of downregulation of CYP3A protein and mRNA levels.
      Decreases in CYP3A activity can be reversed by coadministration with BX. 

PMID- 25371697
TI  - The Effect of Temperature on Pressurised Hot Water Extraction of
      Pharmacologically Important Metabolites as Analysed by UPLC-qTOF-MS and PCA.
AB  - Metabolite extraction methods have been shown to be a critical consideration for
      pharmacometabolomics studies and, as such, optimization and development of new
      extraction methods are crucial. In the current study, an organic solvent-free
      method, namely, pressurised hot water extraction (PHWE), was used to extract
      pharmacologically important metabolites from dried Moringa oleifera leaves. Here,
      the temperature of the extraction solvent (pure water) was altered while keeping
      other factors constant using a homemade PHWE system. Samples extracted at
      different temperatures (50, 100, and 150 degrees C) were assayed for antioxidant
      activities and the effect of the temperature on the extraction process was
      evaluated. The samples were further analysed by mass spectrometry to elucidate
      their metabolite compositions. Principal component analysis (PCA) evaluation of
      the UPLC-MS data showed distinctive differential metabolite patterns. Here,
      temperature changes during PHWE were shown to affect the levels of metabolites
      with known pharmacological activities, such as chlorogenic acids and flavonoids.
      Our overall findings suggest that, if not well optimised, the extraction
      temperature could compromise the "pharmacological potency" of the extracts. The
      use of MS in combination with PCA was furthermore shown to be an excellent
      approach to evaluate the quality and content of pharmacologically important
      extracts. 

PMID- 25371698
TI  - P6 Electroacupuncture Improved QTc Interval Prolongation by Upregulation of
      Connexin43 in Droperidol Treated Rats.
AB  - Aim. This study investigated the effect of P6 EA on droperidol-induced QTc
      interval prolongation and Cx43 expression in ventricular muscle of rats. Methods.
      Twenty-four rats were randomly divided into control group (C), droperidol group
      (D), or EA group (E). C group rats were injected with normal saline. D group rats
      were injected with droperidol 0.13 mg/kg. E group rats were pretreated with EA at
      left P6 acupoint for 30 min and then injected with droperidol (0.13 mg/kg). QTc
      intervals were recorded at lead II in ECG within 120 min. Cx43 expression was
      measured by RT-PCR and western blotting. Result. Droperidol significantly
      prolonged QTc intervals compared with controls at 5 min, 10 min, 15 min, and 30
      min (P < 0.05). P6 EA could significantly abbreviate the prolongation of QTc
      interval compared with droperidol group at 5 min, 10 min, 15 min, and 30 min (P <
      0.05). Cx43 mRNA and proteins were significantly increased by P6 EA compared with
      droperidol group at 120 min (P < 0.05). There were no significant differences in
      Cx43 mRNA and protein expression between droperidol and control group at 120 min
      (P > 0.05). Conclusion. P6 EA could improve QTc interval prolongation induced by
      droperidol, which may relate to upregulation of Cx43 mRNA and protein. Antiemetic
      dose of droperidol had minor effects on Cx43 mRNA and protein expression at 120
      min. 

PMID- 25371699
TI  - The role of juvenile hormone in dominance behavior, reproduction and cuticular
      pheromone signaling in the caste-flexible epiponine wasp, Synoeca surinama.
AB  - BACKGROUND: The popular view on insect sociality is that of a harmonious division
      of labor among two morphologically distinct and functionally non-overlapping
      castes. But this is a highly derived state and not a prerequisite for a
      functional society. Rather, caste-flexibility is a central feature in many
      eusocial wasps, where adult females have the potential to become queens or
      workers, depending on the social environment. In non-swarming paper wasps (e.g.,
      Polistes), prospective queens fight one another to assert their dominance, with
      losers becoming workers if they remain on the nest. This aggression is fueled by
      juvenile hormone (JH) and ecdysteroids, major factors involved in caste
      differentiation in most eusocial insects. We tested whether these hormones have
      conserved aggression-promoting functions in Synoeca surinama, a caste-flexible
      swarm-founding wasp (Epiponini) where reproductive competition is high and
      aggressive displays are common. RESULTS: We observed the behavioral interactions
      of S. surinama females in field nests before and after we had removed the egg
      laying queen(s). We measured the ovarian reproductive status, hemolymph JH and
      ecdysteroid titers, ovarian ecdysteroid content, and analyzed the cuticular
      hydrocarbon (CHC) composition of females engaged in competitive interactions in
      both queenright and queenless contexts. These data, in combination with hormone
      manipulation experiments, revealed that neither JH nor ecdysteroids are necessary
      for the expression of dominance behaviors in S. surinama. Instead, we show that
      JH likely functions as a gonadotropin and directly modifies the cuticular
      hydrocarbon blend of young workers to match that of a reproductive. Hemolymph
      ecdysteroids, in contrast, are not different between queens and workers despite
      great differences in ovarian ecdysteroid content. CONCLUSIONS: The endocrine
      profile of S. surinama shows surprising differences from those of other caste
      flexible wasps, although a rise in JH titers in replacement queens is a common
      theme. Extensive remodeling of hormone functions is also evident in the highly
      eusocial bees, which has been attributed to the evolution of morphologically
      defined castes. Our results show that hormones which regulate caste-plasticity
      can lose these roles even while caste-plasticity is preserved.

PMID- 25371700
TI  - An effective way of J wave separation based on multilayer NMF.
AB  - J wave is getting more and more important in the clinical diagnosis as a new
      index of the electrocardiogram (ECG) of ventricular bipolar, but its signal often
      mixed in normal ST segment, using the traditional electrocardiograph, and
      diagnosed by experience cannot meet the practical requirements. Therefore, a new
      method of multilayer nonnegative matrix factorization (NMF) in this paper is put
      forward, taking the hump shape J wave, for example, which can extract the
      original J wave signal from the ST segment and analyze the accuracy of
      extraction, showing the characteristics of hump shape J wave from the aspects of
      frequency domain, power spectrum, and spectral type, providing the basis for
      clinical diagnosis and increasing the reliability of the diagnosis of J wave. 

PMID- 25371701
TI  - 3D texture analysis in renal cell carcinoma tissue image grading.
AB  - One of the most significant processes in cancer cell and tissue image analysis is
      the efficient extraction of features for grading purposes. This research applied
      two types of three-dimensional texture analysis methods to the extraction of
      feature values from renal cell carcinoma tissue images, and then evaluated the
      validity of the methods statistically through grade classification. First, we
      used a confocal laser scanning microscope to obtain image slices of four grades
      of renal cell carcinoma, which were then reconstructed into 3D volumes. Next, we
      extracted quantitative values using a 3D gray level cooccurrence matrix (GLCM)
      and a 3D wavelet based on two types of basis functions. To evaluate their
      validity, we predefined 6 different statistical classifiers and applied these to
      the extracted feature sets. In the grade classification results, 3D Haar wavelet
      texture features combined with principal component analysis showed the best
      discrimination results. Classification using 3D wavelet texture features was
      significantly better than 3D GLCM, suggesting that the former has potential for
      use in a computer-based grading system. 

PMID- 25371702
TI  - A statistical-textural-features based approach for classification of solid drugs
      using surface microscopic images.
AB  - The quality of pharmaceutical products plays an important role in pharmaceutical
      industry as well as in our lives. Usage of defective tablets can be harmful for
      patients. In this research we proposed a nondestructive method to identify
      defective and nondefective tablets using their surface morphology. Three
      different environmental factors temperature, humidity and moisture are analyzed
      to evaluate the performance of the proposed method. Multiple textural features
      are extracted from the surface of the defective and nondefective tablets. These
      textural features are gray level cooccurrence matrix, run length matrix,
      histogram, autoregressive model and HAAR wavelet. Total textural features
      extracted from images are 281. We performed an analysis on all those 281, top 15,
      and top 2 features. Top 15 features are extracted using three different feature
      reduction techniques: chi-square, gain ratio and relief-F. In this research we
      have used three different classifiers: support vector machine, K-nearest
      neighbors and naive Bayes to calculate the accuracies against proposed method
      using two experiments, that is, leave-one-out cross-validation technique and
      train test models. We tested each classifier against all selected features and
      then performed the comparison of their results. The experimental work resulted in
      that in most of the cases SVM performed better than the other two classifiers. 

PMID- 25371704
TI  - Compressed sensing MR image reconstruction exploiting TGV and wavelet sparsity.
AB  - Compressed sensing (CS) based methods make it possible to reconstruct magnetic
      resonance (MR) images from undersampled measurements, which is known as CS-MRI.
      The reference-driven CS-MRI reconstruction schemes can further decrease the
      sampling ratio by exploiting the sparsity of the difference image between the
      target and the reference MR images in pixel domain. Unfortunately existing
      methods do not work well given that contrast changes are incorrectly estimated or
      motion compensation is inaccurate. In this paper, we propose to reconstruct MR
      images by utilizing the sparsity of the difference image between the target and
      the motion-compensated reference images in wavelet transform and gradient
      domains. The idea is attractive because it requires neither the estimation of the
      contrast changes nor multiple times motion compensations. In addition, we apply
      total generalized variation (TGV) regularization to eliminate the staircasing
      artifacts caused by conventional total variation (TV). Fast composite splitting
      algorithm (FCSA) is used to solve the proposed reconstruction problem in order to
      improve computational efficiency. Experimental results demonstrate that the
      proposed method can not only reduce the computational cost but also decrease
      sampling ratio or improve the reconstruction quality alternatively. 

PMID- 25371703
TI  - Systematic analysis of time-series gene expression data on tumor cell-selective
      apoptotic responses to HDAC inhibitors.
AB  - SAHA (suberoylanilide hydroxamic acid or vorinostat) is the first nonselective
      histone deacetylase (HDAC) inhibitor approved by the US Food and Drug
      Administration (FDA). SAHA affects histone acetylation in chromatin and a variety
      of nonhistone substrates, thus influencing many cellular processes. In
      particularly, SAHA induces selective apoptosis of tumor cells, although the
      mechanism is not well understood. A series of microarray experiments was recently
      conducted to investigate tumor cell-selective proapoptotic transcriptional
      responses induced by SAHA. Based on that gene expression time series, we propose
      a novel framework for detailed analysis of the mechanism of tumor cell apoptosis
      selectively induced by SAHA. Our analyses indicated that SAHA selectively
      disrupted the DNA damage response, cell cycle, p53 expression, and mitochondrial
      integrity of tumor samples to induce selective tumor cell apoptosis. Our results
      suggest a possible regulation network. Our research extends the existing
      research. 

PMID- 25371705
TI  - Boronic acids for sensing and other applications - a mini-review of papers
      published in 2013.
AB  - Boronic acids are increasingly utilised in diverse areas of research. Including
      the interactions of boronic acids with diols and strong Lewis bases as fluoride
      or cyanide anions, which leads to their utility in various sensing applications.
      The sensing applications can be homogeneous assays or heterogeneous detection.
      Detection can be at the interface of the sensing material or within the bulk
      sample. Furthermore, the key interaction of boronic acids with diols allows
      utilisation in various areas ranging from biological labelling, protein
      manipulation and modification, separation and the development of therapeutics.
      All the above uses and applications are covered by this mini-review of papers
      published during 2013. 

PMID- 25371706
TI  - Natural history of ovarian cancer.
AB  - Ovarian cancer is a disease laden with paradigms, and it is a serious health
      problem. It is important to know its natural history, as it is multifactorial in
      origin, and also to understand its behaviour given its risk factors which can
      lead to death from metastasis in patients. It continues to be a challenge for
      oncologists. An analytical literature review was performed to update the latest
      concepts of its origin, evolution, risk factors, pre-clinical horizon, and its
      clinical manifestations; until the death of the patient. 

PMID- 25371707
TI  - Primary renal lymphoma-a case report.
AB  - Primary renal lymphoma is a rare entity representing less than 1% of lesions in
      the kidney. We present the case of a 42-year-old male who was evaluated for pain
      and a mass in the abdomen. The computed tomogram of the abdomen showed a large
      lobulated homogeneously enhancing mass lesion of about 14*12*18 cm, involving the
      whole of the left kidney and encasing the left renal vessels and ureter. The
      patient underwent a biopsy, and the histopathology was diffuse large B cell
      lymphoma, positive for LCA, CD20, PAX 5, Bcl 2 and negative for SIgM, CD33, CD34,
      CD5, Tdt, with MIB 1 labelling index of 40%. He received chemotherapy with
      rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R CHOP)
      for eight cycles followed by radiation to the residual mass and achieved complete
      remission. Currently, he is alive and in remission at 28 months. 

PMID- 25371708
TI  - Patient preferences for disease-modifying drugs in multiple sclerosis therapy: a
      choice-based conjoint analysis.
AB  - OBJECTIVES: With an increasing number of disease-modifying treatments (DMTs) for
      multiple sclerosis (MS), patient preferences will gain importance in the decision
      making process. We assessed patients' implicit preferences for oral versus
      parenteral DMTs and identified factors influencing patients' treatment
      preference. METHODS: Patients with relapsing-remitting MS (n = 156) completed a
      questionnaire assessing treatment preferences, whereby they had to decide between
      pairs of hypothetical treatment scenarios. Based on this questionnaire a choice
      based conjoint analysis was conducted. RESULTS: Treatment frequency and route of
      administration showed a stronger influence on patient preference compared with
      frequency of mild side effects. The latter attribute was more important for
      treatment-naive patients compared with DMT-experienced patients. The higher the
      Extended Disability Status Scale score, the more likely pills, and the less
      likely fewer side effects were preferred. Pills were preferred over injections by
      93% of patients, when treatment frequency and frequency of side effects were held
      constant. However, preference switched to injections when pills had to be taken
      three times daily and injections only once per week. Injections were also
      preferred when pills were associated with frequent side effects. CONCLUSIONS: Our
      results suggest that route of administration and treatment frequency play an
      important role in the patients' preference for a given DMT.

PMID- 25371709
TI  - High noon back pain- severe pseudoradicular pain as a lead symptom of superficial
      siderosis: a case report.
AB  - A superficial siderosis of the central nervous system following a traumatic
      cervical nerve root avulsion usually leads to gait difficulties and hearing loss,
      whereas back pain is described only rarely. Here we report on the first case with
      circadian occurrence of severe back pain as the only symptom of a superficial
      siderosis. We present a case with the most severe pseudoradicular lumbosacral
      pain occurring daily at noon for the past 5 weeks. The 48-year-old male white
      patient did not complain of pain in the morning. A traumatic root avulsion 26
      years earlier led to a brachial plexus palsy and Horner's syndrome in this
      patient. Superficial hemosiderosis in cranial MRI and examination of the
      cerebrospinal fluid revealing massive red blood cells as well as xanthochromia
      and elevated protein levels (742 mg/l) led to the diagnosis of a superficial
      siderosis. A pseudomeningocele caused by a cervical nerve root avulsion is
      described as a rare reason for superficial siderosis. Surgery on a
      pseudomeningocele, diagnosed by MRI, led to an immediate disappearance of
      complaints in our case. Regular neurological investigation and possibly repeated
      lumbar puncture to exclude superficial siderosis should be considered in cases
      with severe back pain and a history of traumatic root avulsion. Modern
      susceptibility weighted MR imaging (SWI) techniques, sensible to the detection of
      superficial hemosiderosis, might be helpful in the making of a diagnosis. 

PMID- 25371710
TI  - Evidence for the efficacy of interferon beta-1b in delaying the onset of
      clinically definite multiple sclerosis in individuals with clinically isolated
      syndrome.
AB  - The BEtaferon(r)/BEtaseron(r) in Newly Emerging MS For Initial Treatment
      (BENEFIT) trial assessed the efficacy of early versus delayed treatment with
      interferon beta-1b for patients with clinically isolated syndrome (CIS). Patients
      were randomly assigned to receive either interferon beta-1b 250 MUg every other
      day (early treatment, n = 292) or placebo (delayed treatment, n = 176) for 2
      years or until progression to clinically definite multiple sclerosis. Clinical
      and magnetic resonance imaging (MRI) outcomes were assessed after 2 years (at the
      end of the placebo-controlled phase) and then again at 3, 5, and 8 years post
      randomization. MRI assessments were made after 2, 3, and 5 years. The results
      showed a consistent advantage of early treatment across most clinical and MRI
      variables, although median Expanded Disability Status Scale scores remained
      consistently low, with no differences between groups. These findings suggest that
      early treatment with interferon beta-1b improves long-term outcomes for patients
      presenting with CIS. 

PMID- 25371711
TI  - Rituximab postprogressive multifocal leukoencephalopathy: a Feasible therapeutic
      option in selected cases.

PMID- 25371712
TI  - Serum ferritin levels and the development of metabolic syndrome and its
      components: a 6.5-year follow-up study.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      changes in serum ferritin concentrations and the development of metabolic
      syndrome (MetS) and its components over a 6.5 year follow-up period in Finnish
      adults. METHODS: Adults born in Pieksamaki, Finland, in 1942, 1947, 1952, 1957,
      and 1962 (n = 1294) were invited to health checkups between 1997 and 1998 and
      2003 and 2004. All of the required variables for both checkups were available
      from 691 (53%) subjects (289 men and 402 women). MetS was defined by the National
      Cholesterol Education Program criteria. RESULTS: During the 6.5-year follow-up
      period, 122 (18%) subjects developed incident cases of MetS. Increases in serum
      ferritin levels were significantly higher in both women and men with incident
      MetS compared with women and men without MetS (p = 0.04, p = 0.03). Also, serum
      ferritin levels increased significantly less in women in whom the criteria for
      MetS resolved during the follow-up period (p = 0.01). Increases in serum ferritin
      levels were significantly lower in women in whom the glucose criterion for MetS
      resolved, and higher in women for whom the waist criterion developed (p = 0.01
      and p <0.001, respectively). Serum ferritin levels decreased significantly more
      in men in whom the triglyceride criterion for MetS resolved during the follow-up
      period (p = 0.01). There was a clear and significant correlation between change
      in serum ferritin level and change in waist circumference both in men and women
      (p <0.001, p <0.01). In addition, correlations between change in serum ferritin
      level and change in plasma triglyceride as well as glucose levels were strongly
      positive in men (p <0.001). There was negative correlation between change in
      serum ferritin and plasma high density cholesterol level both in men and women.
      CONCLUSIONS: Increases in serum ferritin over a 6,5 year period are associated
      with development of MetS in both men and women. Whereas, lower increases in serum
      ferritin over the same timeframe are associated with resolution of
      hypertriglyceridemia in men and hyperglycemia in women. Increases in waist
      circumference was positively correlated with increases in serum ferritin in both
      men and women.

PMID- 25371713
TI  - microRNAs as novel biomarkers of schizophrenia (Review).
AB  - Schizophrenia is a severe mental illness and the most common complex
      neuropsychiatric disorder. To date, the etiology of schizophrenia is unclear;
      consequently, the diagnosis of schizophrenia is controversial. Biomarkers that
      reflect the dysregulations observed in schizophrenia may potentially assist the
      diagnosis of the disorder. However, the majority of these biomarkers are found in
      the brain tissue, which is not readily accessible, leading to the search for
      novel biomarkers that are present in the peripheral blood. microRNAs (miRNAs) are
      small non-coding RNAs that function as post-transcriptional regulators of gene
      expression. Previous investigations have revealed that miRNAs may play a
      potential role in neurodevelopment and maturation, including neurite outgrowth,
      dendritogenesis and dendritic spine formation. These developments highlight the
      significance of miRNAs as potential diagnostic biomarkers for schizophrenia. To
      date, miRNA biomarkers have been predominantly extracted from the brain tissue;
      however, future studies should examine the use of peripheral blood miRNAs as
      biomarkers, as these are more accessible.

PMID- 25371714
TI  - Significance of hypoxia-inducible factor-1alpha expression with atrial fibrosis
      in rats induced with isoproterenol.
AB  - Atrial interstitial fibrosis plays a dual role in inducing and maintaining atrial
      fibrillation (AF). Hypoxia-inducible factor-1alpha (HIF-1alpha) has been reported
      as closely associated with renal, liver and pulmonary fibrosis diseases. However,
      whether HIF-1alpha is involved in myocardial fibrosis, and the associations
      between HIF-1alpha, transforming growth factor-beta1 (TGF-beta1) and matrix
      metalloproteinase-9 (MMP-9) remain unknown. Therefore, this area warrants
      studying for the significance of AF diagnosis and treatment. The present study
      investigated the expression of HIF-1alpha in atrial fibrosis and its possible
      mechanism in isoproterenol (ISO)-induced rats. The three groups of rats; control,
      ISO and ISO plus sirolimus [also known as rapamycin (Rapa)], were treated for 15
      days and sacrificed to remove the myocardial tissues. The expression levels of
      HIF-1alpha, TGF-beta1 and MMP-9 and their associations with atrial fibrosis were
      examined through histomorphology and protein and mRNA levels. The protein and
      mRNA levels of HIF-1alpha, TGF-beta1 and MMP-9 in the ISO group were increased
      markedly (P<0.01) compared with the control group, while those in the Rapa group
      were clearly decreased (P<0.01) compared with the ISO group. The protein and mRNA
      levels of HIF-1alpha, TGF-beta1 and MMP-9 were positively correlated (P<0.01)
      with atrial fibrosis (collagen volume fraction index), as were the HIF-1alpha,
      TGF-beta1 and MMP-9 mRNA levels (P<0.01) and the mRNA levels between MMP-9 and
      TGF-beta1 (P<0.01). During the process of atrial fibrosis in ISO-induced rats,
      HIF-1alpha promotes the expression of TGF-beta1 and MMP-9 protein, and thus is
      involved in in atrial fibrosis.

PMID- 25371715
TI  - Effect of rosuvastatin on hyperuricemic rats and the protective effect on
      endothelial dysfunction.
AB  - Endothelial dysfunction plays a key role in the development of cardiovascular
      diseases, renal injuries and hypertension induced by hyperuricemia. Therapies
      targeting uric acid (UA) may be beneficial in cardiovascular diseases. In the
      present study, the effect of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme
      A reductase inhibitor, was investigated to determine whether rosuvastatin
      improves endothelial dysfunction via the endothelial nitric oxide (NO) pathway
      and delays the pathogenesis of endothelial dysfunction in hyperuricemic rats. A
      total of 72 Sprague-Dawley rats (age, 8 weeks) were randomly divided into six
      groups (12 rats per group), including the control, model, 2.5 mg/kg/day
      rosuvastatin, 5 mg/kg/day rosuvastatin, 10 mg/kg/day rosuvastatin and 53.57
      mg/kg/day allopurinol groups. The model, rosuvastatin and allopurinol rats were
      subjected to hyperuricemia, induced by the administration of yeast extract powder
      (21 g/kg/day) and oxonic acid potassium salt (200 mg/kg/day). The hyperuricemic
      rats were treated with 2.5, 5.0 or 10.0 mg/kg/day rosuvastatin orally for six
      weeks, while rats treated with allopurinol (53.57 mg/kg/day) were used as a
      positive control. The serum levels of NO and the gene expression levels of
      endothelial NO synthase in the aortic tissue increased, whereas the serum levels
      of UA, endothelin-1 and angiotensin II decreased in the hyperuricemic rats
      treated with rosuvastatin, particularly at a high rosuvastatin dose (10
      mg/kg/day). In addition, the curative effect of the 10 mg/kg/day rosuvastatin
      group was evidently higher compared with the allopurinol group. Therefore,
      rosuvastatin may be a novel drug candidate for the treatment of hyperuricemia due
      to its endothelial protective properties.

PMID- 25371716
TI  - Intermittent low-dose digoxin may be effective and safe in patients with chronic
      heart failure undergoing maintenance hemodialysis.
AB  - A low dose of digoxin is known to reduce mortality and hospitalization in
      patients with heart failure; however, the safety of digoxin in treating patients
      with heart failure on maintenance hemodialysis remains controversial. The
      objective of this study was to determine the effectiveness and safety of digoxin
      at lower doses in patients with heart failure on maintenance hemodialysis using a
      retrospective cohort study. This study included 67 heart-failure patients on
      maintenance hemodialysis: Twenty-four patients received intermittent low doses of
      digoxin (ILDD), 23 patients received continuous low doses of digoxin (CLDD) and
      the remaining patients were used as a control group without digoxin treatment.
      The brain natriuretic peptide (BNP) level and serum digoxin concentrations (SDCs)
      were measured by ELISA and the changes in left ventricular end diastolic diameter
      (LVEDD), left ventricular ejection fraction (LVEF), cardiac output (CO) and heart
      rate (HR) were evaluated by two-dimensional echocardiography. The symptoms of
      digoxin toxicity were monitored in the treated patients. Compared with the
      control group, LVEDD, BNP and HR decreased significantly between days 0 and 60 in
      the ILDD and CLDD groups, but LVEF and CO increased between days 0 and 60 in the
      same groups (all P<0.05). The levels of BNP and the LVEDD, CO, LVEF and HR were
      not significantly different between the ILDD and CLDD groups (P>0.05).
      Furthermore, and the mean SDC of the ILDD group was lower than that of the CLDD
      group. In the ILDD group, no patients had apparent symptoms of toxicity, but four
      patients developed digoxin toxicity in the CLDD group. In conclusion an
      intermittent lower dose of digoxin has beneficial effects and clinical safety in
      hemodialysis patients with congestive heart failure.

PMID- 25371717
TI  - Analysis of tumor necrosis factor alpha-induced and nuclear factor kappaB
      silenced LNCaP prostate cancer cells by RT-qPCR.
AB  - Prostate cancer is the second leading cause of morbidity and mortality in males
      in the Western world. In the present study, LNCaP, which is an androgen receptor
      positive and androgen-responsive prostate cancer cell line derived from lymph
      node metastasis, and DU145, which is an androgen receptor-negative prostate
      cancer cell line derived from brain metastasis, were investigated. TNFalpha
      treatment decreased p105 and p50 expression and R1881 treatment slightly
      decreased p105 expression but increased p50 expression with or without TNFalpha
      induction. As an aggressive prostate cancer cell line, DU145 transfected with six
      transmembrane protein of prostate (STAMP)1 or STAMP2 was also exposed to
      TNFalpha. Western blotting indicated that transfection with either STAMP gene
      caused a significant increase in NFkappaB expression following TNFalpha
      induction. In addition, following the treatment of LNCaP cells with TNFalpha,
      reverse transcription quantitative polymerase chain reaction (RT-qPCR) was
      performed with a panel of apoptosis-related gene primers. The apoptosis-related
      genes p53, p73, caspase 7 and caspase 9 showed statistically significant
      increases in expression levels while the expression levels of MDM2 and STAMP1
      decreased following TNFalpha induction. Furthermore, LNCaP cells were transfected
      with a small interfering NFkappaB (siNFkappaB) construct for 1 and 4 days and
      induced with TNFalpha for the final 24 h. RT-qPCR amplifications were performed
      with apoptosis-related gene primers, including p53, caspases and STAMPs. However,
      no changes in the level of STAMP2 were observed between cells in the presence or
      absence of TNFalpha induction or between those transfected or not transfected
      with siNFkappaB; however, the level of STAMP1 was significantly decreased by
      TNFalpha induction, and significantly increased with siNFkappaB transfection.
      Silencing of the survival gene NFkappaB caused anti-apoptotic STAMP1 expression
      to increase, which repressed p53, together with MDM2. NFkappaB silencing had
      varying effects on a panel of cancer regulatory genes. Therefore, the effective
      inhibition of NFkappaB may be critical in providing a targeted pathway for
      prostate cancer prevention.

PMID- 25371718
TI  - Human leukocyte antigen G and miR-148a are associated with the pathogenesis of
      intrahepatic cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy (ICP) occurs mainly during the third
      trimester of gestation and is characterized by pruritus and elevated serum bile
      acid levels. The pathogenesis of this disease has yet to be elucidated. The
      nonclassical human leukocyte antigen G (HLA-G) is a trophoblast-specific molecule
      and is involved in the regulation of maternal immune response at the maternal
      fetal interface. MicroRNAs (miRNAs) have an important role in a number of
      physiological and pathological processes. However, the roles of HLA-G and miRNAs
      in immune response in the pathogenesis of ICP have yet to be elucidated. In the
      present study, the expression of HLA-G and miR-148a in the placenta of patients
      with ICP was investigated. The mRNA and protein expression levels of HLA-G were
      markedly reduced in the placenta of patients with ICP compared with the levels in
      healthy pregnant females, and were negatively correlated with serum total bile
      acid (TBA) levels. It was also observed that miR-148a levels were markedly
      upregulated in the placenta and peripheral blood of patients with ICP.
      Furthermore, the mRNA and protein expression levels of HLA-G in the placenta were
      negatively correlated with the miR-148 levels in the placenta, but not in the
      peripheral blood, while the miR-148a levels in the placenta were positively
      correlated with serum TBA levels. These results suggest that the downregulation
      of HLA-G is probably caused by the upregulation of miR-148a in the placenta, and
      miR-148a in the placenta may contribute to the pathogenesis of ICP via the
      inhibition of HLA-G expression.

PMID- 25371719
TI  - Dihydroartemisinin inhibits vascular endothelial growth factor-induced
      endothelial cell migration by a p38 mitogen-activated protein kinase-independent
      pathway.
AB  - Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has been
      demonstrated to possess a strong antiangiogenic activity. However, the molecular
      mechanisms underlying this effect remain unclear. Endothelial cell (EC) migration
      is an essential component of angiogenesis, and the p38 mitogen-activated protein
      kinase (MAPK) signaling pathway plays a key role in the regulation of migration
      induced by vascular endothelial growth factor (VEGF). The aim of the present
      study was to investigate the effects of DHA on EC migration and the p38 MAPK
      signaling pathway. Human umbilical vein ECs (HUVECs) were treated with DHA and
      VEGF-induced migration was analyzed. The activation of p38 MAPK was detected by
      western blot analysis, and the migration assays were performed with a p38
      specific inhibitor, SB203850. It was revealed that 20 MUM DHA significantly
      reduced EC migration in the transwell migration assay, wound healing assay and
      electrical cell-substrate impedance sensing real-time analysis. However, DHA did
      not affect p38 MAPK phosphorylation or expression. In the absence or presence of
      SB203850, DHA induced a similar proportional reduction of EC migration in the
      three migration assays. Therefore, the present study demonstrated that DHA
      inhibits VEGF-induced EC migration via a p38 MAPK-independent pathway.

PMID- 25371720
TI  - Sensory Guillain-Barre syndrome: A case report.
AB  - A 58-year-old female exhibited the onset of symmetrical sensory abnormalities of
      the face and extremities. The neurological examination revealed normal muscle
      strength with abated or absent tendon reflexes. The patient experienced
      symmetrical glove- and stocking-type pinprick sensations in the distal
      extremities and a loss of temperature sensation, but had normal proprioception
      and vibration senses and joint topesthesia. The lumbar puncture showed protein
      cell separation at the fifth week after the onset of symptoms. At the same time
      point, the electrophysiological examination showed demyelination changes
      involving the trigeminal nerve and the somatic motor nerve. Needle
      electromyography revealed normal results. The clinical symptoms ceased
      progression at the fourth week after symptom onset, and began to improve from the
      sixth. This case was considered to be sensory Guillain-Barre syndrome, which was
      characterized by its cranial nerve involvement.

PMID- 25371721
TI  - Mild hypothermia in combination with minimally invasive evacuation of hematoma
      reduces inflammatory damage in patients via the nuclear factor-kappaB pathway.
AB  - The aim of this study was to investigate the effects of mild hypothermia and
      minimally invasive evacuation of hematoma on the brain function of patients with
      cerebral hemorrhage. Seventy-six patients with acute cerebral hemorrhage were
      divided into the minimally invasive evacuation of hematoma (MIHE) and mild
      hypothermia and minimally invasive evacuation of hematoma (MHMIHE) groups.
      National Institutes of Health Stroke Scale (NIHSS) scores on the day of admission
      of the patient and one, three and seven days after the procedure were recorded.
      Perihematoma brain tissue morphology was observed using hematoxylin and eosin
      staining. Nuclear factor-kappaB (NF-kappaB) expression was determined by
      immunohistochemistry. The tumor necrosis factor-alpha (TNF-alpha) level was
      detected by ELISA. NIHSS scores in the MHMIHE group were significantly lower than
      those in the MIHE group on days three and seven. TNF-alpha and NF-kappaB levels
      peaked on day three, and the MHMIHE group had significantly lower levels of TNF
      alpha and NF-kappaB than the MIHE group. In conclusion, the present study
      demonstrated that mild hypothermia and minimally invasive evacuation of hematoma
      can effectively reduce inflammation and improve the brain function of patients.

PMID- 25371722
TI  - Effect of Avastin on the number and structure of tumor blood vessels of nude mice
      with A549 lung adenocarcinoma.
AB  - The aim of the present study was to investigate the effect of Avastin on the
      number and structure of tumor blood vessels of nude mice with A549 lung
      adenocarcinoma. A total of 30 nude mice were randomly divided into three groups,
      namely the control, the Avastin I (Avastin 3 mg/kg) and the Avastin II (Avastin 6
      mg/kg) groups. Following treatment, ELISA was used to detect the expression level
      of vascular endothelial growth factor (VEGF) in tumor tissues. The microvascular
      density in tumor tissues and tumor vascular pericyte coverage was detected by
      immunofluorescence. The tumor growth and survival rate of mice in the three
      groups were also analyzed. Compared with the control group, the Avastin I and II
      groups exhibited significantly decreased VEGF levels and microvascular density in
      the tumor tissues, with the decrease in the Avastin II group being more prominent
      (P<0.05). After 7 days of treatment, the vascular pericyte coverage in the tumor
      tissues of mice in the Avastin I and II groups was significantly increased
      compared with that in the control group mice (P<0.05). Compared with the control
      group, the mice in the Avastin I and II groups exhibited a significantly
      decreased tumor growth rate and this effect was dose-dependent. The survival rate
      of mice in the Avastin I and II groups was significantly increased compared with
      that of the mice in the control group (P<0.05). In conclusion, Avastin
      significantly decreased the microvascular density of the tumor in nude mice with
      A549 lung adenocarcinoma and also significantly increased tumor vascular pericyte
      coverage, inhibited tumor growth and increased the survival rate of the mice,
      through its potent antiangiogenic activity.

PMID- 25371723
TI  - Effectiveness and safety of endoscopy for treatment of surgical site infection: A
      randomized control trial.
AB  - The aim of this randomized control study was to evaluate the effectiveness and
      safety of endoscopy for the treatment of surgical site infection (SSI), compared
      with conventional therapy. One hundred and six patients who were diagnosed with
      severe SSI were included in the study, performed from May 2005 to July 2012 at
      Tianjin Binhai New Area Dagang Hospital, China. Patients were randomly divided
      into two groups: 57 patients in group A treated by endoscopy and 49 patients in
      group B treated by conventional therapy for SSI. The primary outcome was the
      healing period of the wound; the secondary outcomes were the blood loss following
      surgery, visual analog scale (VAS) measurement, volume of irrigation saline
      during surgery, rate of skin transplantation, length of hospital stay and other
      complications. The mean wound healing time was significantly less in group A
      (10.0+/-2.5 days) than in group B (19.4+/-5.2 days). The mean VAS score 7 days
      after surgery in group A was significantly less compared with group B. The intra
      operative blood loss, intra-operative volume of irrigation saline and length of
      the hospital stay were significantly reduced in group A compared with group B. No
      significant differences between the groups were revealed in terms of the duration
      of surgery and the clinical complications. This study demonstrated that the
      endoscopy procedure for the treatment of SSI reduces the wound healing time
      compared with that of traditional surgery, without increasing any risk of
      clinical events. The present study showed that endoscopy was not only effective
      but also safe in the therapy of serious SSI. However, a further randomized
      control trial is necessary to testify our conclusions.

PMID- 25371724
TI  - N-methyl-D-aspartate receptor antagonist MK-801 prevents apoptosis in rats that
      have undergone fetal spinal cord transplantation following spinal hemisection.
AB  - Spinal cord injury is the main cause of paraplegia, but effective therapies for
      it are lacking. Embryonic spinal cord transplantation is able to repair spinal
      cord injury, albeit with a large amount of neuronal apoptosis remaining in the
      spinal cord. MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, is able
      to reduce cell death by decreasing the concentration of excitatory amino acids
      and preventing extracellular calcium ion influx. In this study, the effect of MK
      801 on the apoptosis of spinal cord neurons in rats that have received a fetal
      spinal cord (FSC) transplant following spinal hemisection was investigated.
      Wistar rats were divided into three groups: Spinal cord hemisection injury with a
      combination of FSC transplantation and MK-801 treatment (group A); spinal cord
      hemisection injury with FSC transplantation (group B); and spinal cord injury
      with insertion of a Gelfoam pledget (group C). The rats were sacrificed 1, 3, 7
      and 14 days after the surgery. Apoptosis in spinal slices from the injured spinal
      cord was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick end labeling reaction, and the expression of B-cell lymphoma-2 (Bcl-2) was
      measured by immunohistochemistry. The positive cells were quantitatively analyzed
      using a computer image analysis system. The rate of apoptosis and the positive
      expression of Bcl-2 protein in the spinal cord neurons in the three groups
      decreased in the following order: C>B>A (P<0.05) and A>B>C (P<0.05),
      respectively. This indicates that treatment with the NMDA receptor antagonist MK
      801 prevents apoptosis in the spinal cord neurons of rats that have undergone FSC
      transplantation following spinal hemisection.

PMID- 25371725
TI  - Red yeast rice repairs kidney damage and reduces inflammatory transcription
      factors in rat models of hyperlipidemia.
AB  - Xuezhikang (XZK), an extract of red yeast rice, has been widely used for the
      management of hyperlipidemia and coronary heart disease (CHD); however, the
      effects of XZK treatment on kidney injury have not yet been fully identified. The
      aim of the current study was to evaluate the effects of XZK on the kidneys and
      investigate the related mechanisms in a rat model of hyperlipidemia. Thus, the
      effect on inflammatory transcription factors and kidney damage was investigated
      with in vitro and in vivo experiments on hyperlipidemic rats following XZK
      treatment. The results revealed that the plasma levels of total cholesterol (TC),
      triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C) were
      significantly decreased, while the levels of high-density lipoprotein-cholesterol
      (HDL-C) were significantly upregulated in the XZK treatment group, as compared
      with those in the hyperlipidemia group (P<0.05). In addition, the results
      demonstrated that XZK was able to repair the kidney damage caused by
      hyperlipidemia. Furthermore, the expression levels of the inflammatory
      transcription factors, tumor necrosis factor-alpha and interleukin-6, were shown
      to be reduced in the XZK group when compared with the hyperlipidemia group. In
      summary, XZK reduces kidney injury, downregulates the levels of TG, TC and LDL-C,
      as well as the expression levels of inflammatory transcription factors, and
      upregulates HDL-C. These results further the understanding of the molecular
      pathogenic mechanisms underlying hyperlipidemia and aid the development of XZK as
      an effective therapeutic agent for hyperlipidemia.

PMID- 25371726
TI  - Chromodomain helicase/ATPase DNA binding protein 1-like protein expression
      predicts poor prognosis in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a malignancy with a high metastatic ability.
      Recent studies have implicated the role of chromodomain helicase/ATPase DNA
      binding protein 1-like (CHD1L) gene as a novel oncogene; however, the functional
      role of CHD1L in NPC remains unknown. The aim of this study was to evaluate the
      clinical significance of CHD1L positivity in NPC. CHD1L protein expression was
      examined by performing western blot analysis of 30 fresh NPC tissues and
      conducting immunohistochemistry tests of 133 NPC samples between December 1, 2005
      and December 1, 2009. The correlations of CHD1L expression status with
      clinicopathological features and prognosis were investigated. Immunohistochemical
      analysis showed that 88 of 133 (66.2%) paraffin-embedded NPC biopsies exhibited
      positive expression of CHD1L, but all non-cancerous nasopharyngeal specimens were
      negative for CHD1L expression. In addition, positive CHD1L expression was
      strongly associated with an advanced clinical stage (P=0.016), recurrence
      (P=0.002) and the metastasis status (P=0.031) of NPC. Kaplan-Meier survival
      analysis demonstrated that patients with CHD1L-positive NPC had significantly
      shorter overall survival (P<0.001). Furthermore, the multivariate analysis
      indicated that CHD1L protein expression was an independent prognostic factor for
      overall survival (hazard ratio, 7.916; 95% confidence interval, 2.067-16.034;
      P=0.003) in patients with NPC. These results indicate that CHD1L is a prognostic
      marker for NPC.

PMID- 25371727
TI  - Ginsenoside-Rb3 protects the myocardium from ischemia-reperfusion injury via the
      inhibition of apoptosis in rats.
AB  - Ginsenoside-Rb3 (G-Rb3) has been previously demonstrated to attenuate myocardial
      ischemia-reperfusion injury (MIRI). The aim of the present study was to
      investigate this further and determine whether G-Rb3 protects the myocardium from
      ischemia-reperfusion injury via the inhibition of apoptosis. Adult male Sprague
      Dawley rats were randomly divided into four groups: Sham, MIRI, G-Rb3 treatment
      (orally, 20 mg/kg) and ischemic postconditioning (as the positive control). The
      drug or placebo treatment was administered to the rats once a day for three
      consecutive days, and MIRI was then induced by subjecting the rats to left
      anterior descending coronary artery ligation for 30 min and reperfusion for 2 h.
      The results showed that G-Rb3 treatment significantly reduced the number of
      apoptotic cells in the myocardium and the expression of B-cell lymphoma 2
      associated X protein, and increased the expression of B-cell lymphoma 2. The
      activities of aspartate aminotransferase, lactate dehydrogenase and creatine
      kinase-MB in the serum were also reduced significantly by the G-Rb3 treatment.
      These findings suggest that G-Rb3 inhibits apoptosis in the early stage of MIRI,
      and attenuates MIRI when the reperfusion continues. G-Rb3 was also shown to
      significantly reduce the level of malondialdehyde and increase the activity of
      superoxide dismutase in the myocardium, which suggests that attenuating reactive
      oxygen species accumulation and oxidative stress may be the major mechanism
      underlying the anti-apoptotic effects of G-Rb3. The release of inflammatory
      factors was significantly attenuated by G-Rb3, which may also be associated with
      its anti-apoptotic effects.

PMID- 25371728
TI  - Association between cardiothoracic ratio, left ventricular size and systolic
      function in patients undergoing computed tomography coronary angiography.
AB  - The present study aimed to investigate the association between cardiothoracic
      ratio (CTR) and left ventricular (LV) systolic function parameters in patients
      with or without preserved LV ejection fraction (LVEF). A total of 203 subjects
      suspected with coronary artery disease underwent chest radiography and dual
      source computed tomography coronary angiography (DSCT-CA). The LV systolic
      function parameters: LV end-diastolic volume index (LVEDVI), LV end-systolic
      volume index (LVESVI), and LVEF were measured from the DSCT-CA. The association
      between CTR and LV systolic function parameters was analyzed according to LVEF
      value (<55%, depressed LVEF group; versus >=55%, preserved LVEF group) and CTR
      value (<0.5, normal range CTR group; versus >=0.5, larger CTR group). The LVEDVI
      and LVESVI were higher in the depressed LVEF group compared with the preserved
      LVEF group (108.56+/-57.15 vs. 67.52+/-14.56 ml/m2, P<0.001; and 64.07+/-37.81
      vs. 20.23+/-7.23 ml/m2, P<0.001, respectively) and lower in the normal range CTR
      group compared with the larger CTR group (67.10+/-15.00 vs. 77.30+/-34.32 ml/m2,
      P=0.009 and 21.94+/-8.96 vs. 28.97+/-26.54 ml/m2, P=0.017, respectively).
      Significant correlations were found between CTR and LVEDVI, and LVESVI and LVEF
      in the depressed LVEF group (r=0.66, P<0.001; r=0.65, P<0.001; and r=-0.46,
      P=0.018, respectively). However, there was no significant association detected
      between CTR and LV systolic function parameters in the other subgroups. The
      LVEDVI and LVESVI showed an inverse correlation with the LVEF in each group.
      Although the CTR was not a reliable indicator of LV size and systolic function in
      patients with preserved LVEF, it was correlated with LV size and LVEF in patients
      with depressed LVEF.

PMID- 25371729
TI  - Ozone oxidative preconditioning inhibits renal fibrosis induced by ischemia and
      reperfusion injury in rats.
AB  - Ischemia and reperfusion injury (IRI) is a crucial contributor to the development
      of renal fibrosis. Ozone has been proposed as a novel medical therapy for various
      conditions, including organ IRI. The aim of this study was to investigate whether
      ozone oxidative preconditioning (OzoneOP) has a beneficial effect in preventing
      the development of renal fibrosis following IRI. Sprague Dawley rats were
      subjected to 45 min of ischemia followed by 8 weeks of reperfusion. Prior to
      surgery, rats in the OzoneOP group were treated with ozone and those in the IRI
      and Sham groups were untreated. Blood samples were collected for the detection of
      blood urea nitrogen (BUN) and creatinine (Cr) levels. To assess tissue fibrosis,
      Masson's trichrome staining was performed. Immunohistochemistry was also
      performed to determine the localization of alpha-smooth muscle actin (alpha-SMA).
      Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and
      western blotting were conducted to analyze the expression of transforming growth
      factor (TGF)-beta1, alpha-SMA and Smad7. The levels of BUN and Cr did not
      significantly differ between groups. Rats pretreated with ozone showed markedly
      less interstitial fibrosis than untreated rats following IRI. In addition,
      immunohistochemistry revealed that alpha-SMA expression was attenuated in the
      OzoneOP group compared with the IRI group. RT-qPCR and western blot analysis
      showed that OzoneOP inhibited the IRI-induced increases in alpha-SMA and TGF
      beta1 expression levels, and that the IRI-induced reduction in the expression of
      Smad7 was inhibited in the OzoneOP group. The results indicate that OzoneOP has
      beneficial effects on ischemic renal fibrosis. OzoneOP may exert its protective
      effects by a mechanism involving modulation of the TGF-beta1/Smad7 pathway.

PMID- 25371730
TI  - Diagnosis of infantile myofibromatosis with pseudo-ulcerated plaque using
      prenatal ultrasound: A case report.
AB  - The present case report describes a case of infantile myofibromatosis (IM) with a
      pseudo-ulcerated plaque on the right side of the back of a fetus, detected in the
      38th week of gestation using prenatal ultrasound. The fetus was examined weekly
      by ultrasound to measure the size of the mass. At birth, the scarlet mass was
      slightly elevated compared with the skin around it, with a cavity in the center.
      It appeared similar to an ulcerated plaque, but the surface of the mass was
      intact and smooth with a stratum lucidum. Thus, the mass was indicated to be a
      pseudo-ulcerated plaque. Three months later, the mass had grown larger and so was
      removed by surgery. The pathology of the mass was confirmed as IM. It is
      suggested that IM should be considered when a soft tissue tumor is presented by
      prenatal ultrasound.

PMID- 25371731
TI  - Role of p38 MAPK and STAT3 in lipopolysaccharide-stimulated mouse alveolar
      macrophages.
AB  - Excessive production of inflammatory mediators is an important feature of
      inflammatory lung disease. In macrophages, mitogen-activated protein kinase
      (MAPK) and signal transducer and activator of transcription-3 (STAT3) are crucial
      mediators for the production of proinflammatory cytokines. In the present study,
      the role of MAPK and STAT3 on tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-10 production was investigated in mouse alveolar macrophages. The levels of
      TNF-alpha and IL-10 in lipopolysaccharide (LPS; 100 ng/ml)-stimulated MH-S cell
      lines were measured by an enzyme-linked immunosorbent assay, with or without p38
      inhibitor (SB203580; 5, 10 or 15 MUM) intervention. Phosphorylated STAT3 (p
      STAT3) expression was examined by western blot analysis and immunocytochemistry
      following LPS stimulation for 15 or 30 min. Antibodies against STAT3 were used to
      verify comparable sample loading. Cells stimulated with LPS showed significantly
      increased levels of p-STAT3 protein (P<0.05) when compared with the baseline
      levels. TNF-alpha and IL-10 protein levels also increased following LPS
      stimulation (P<0.05). By contrast, treatment with the p38 inhibitor, SB203580,
      decreased the levels of p-STAT3, TNF-alpha and IL-10 (P<0.05) following LPS
      stimulation. SB203580 was shown to inhibit LPS-stimulated TNF-alpha expression
      (P<0.05) in a concentration-dependent manner, reaching significance at a
      concentration of 10 MUM. However, the inhibition of IL-10 expression was not
      concentration-dependent. Therefore, LPS-stimulated overproduction of TNF-alpha
      and IL-10 is mediated at least partially by the MAPK pathway. Inhibition of p38
      prevented LPS-induced STAT3 phosphorylation, indicating an interaction between
      the STAT3 and MAPK signaling pathways.

PMID- 25371732
TI  - Gadolinium chloride suppresses acute rejection and induces tolerance following
      rat liver transplantation by inhibiting Kupffer-cell activation.
AB  - The aim of the present study was to investigate the mechanism by which gadolinium
      chloride (GdCl3) inhibits Kupffer cell (KC) activation and its ability to
      suppress acute rejection and induce tolerance following liver transplantation in
      rats. Rats were randomly divided into control, liver transplantation with GdCl3
      pretreatment and liver transplantation with normal saline pretreatment groups.
      The survival rate, liver function, hepatic pathological histology, cytokine
      levels in the liver and bile, activity of nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) in KCs, and expression levels of
      membranous molecules on the KCs were observed. It was identified that the one
      month survival rate in the GdCl3 group was significantly higher compared with
      that in the saline group (P<0.05). The liver function in the GdCl3 group
      gradually recovered following transplantation surgery; however, it progressively
      deteriorated in the saline group. There were minor changes of hepatic
      pathological histology in the GdCl3 group, whereas changes typical of acute
      rejection occurred in the saline group. In the GdCl3 group, the levels of
      interferon gamma and interleukin (IL)-2 were significantly lower whereas the
      levels of IL-10 were significantly higher compared with those in the control and
      saline groups (all P<0.01). The IL-4 levels in the GdCl3 and control groups were
      similar. The activity of NF-kappaB in the saline group was significantly higher
      compared with those in the control and GdCl3 groups (P<0.01). The expression
      levels of major histocompatibility complex-II, cluster of differentiation (CD)80
      and CD86 on the KC membranes in the GdCl3 group was significantly lower compared
      with those in the control group (P<0.05); however, these membranous proteins were
      highly expressed in the saline group. These data indicate that GdCl3 efficiently
      inhibits the immunological activity of KCs, suppresses acute rejection and
      induces tolerance following liver allograft transplantation in rats.

PMID- 25371733
TI  - Effects of epigallocatechin gallate on the proliferation and apoptosis of the
      nasopharyngeal carcinoma cell line CNE2.
AB  - The present study explored the effects of epigallocatechin gallate (EGCG) on the
      cell cycle, proliferation and apoptosis of the nasopharyngeal carcinoma cell line
      CNE2 in vitro. The proliferation of CNE2 cells was detected using the cell
      counting kit-8 method. Cell cycle distribution and apoptosis were detected using
      flow cytometry. The human telomerase reverse transcriptase (hTERT) mRNA
      expression was determined using reverse transcription polymerase chain reactions.
      The protein expression of hTERT and Myc proto-oncogene protein (c-Myc) was
      observed using western blot analysis. EGCG inhibited the proliferation of CNE2
      cells in a concentration-dependent manner (P<0.05) and blocked the cell cycle
      progression of the cells. In the low concentration (100 MUg/ml) group, the cell
      cycle arrest showed a time-dependent manner. However, as the concentration
      increased and action time was prolonged, this time dependency became less marked.
      EGCG promoted the apoptosis of CNE2 cells in a time-dependent manner. In
      addition, EGCG downregulated the mRNA and protein expression of hTERT and
      downregulated the expression of c-Myc protein. Downregulation of the expression
      of hTERT and c-Myc was more evident in the high-dose group (200 MUg/mL). In
      conclusion, EGCG has proliferation-inhibiting, cell cycle-blocking and apoptosis
      promoting effects on CNE2 cells. EGCG may be developed into an auxiliary
      therapeutic agent for the treatment of nasopharyngeal carcinoma.

PMID- 25371734
TI  - Late onset oral treatment with tranilast following large myocardial infarction
      has no beneficial effects on cardiac remodeling and mortality in rats.
AB  - Tranilast (Tra) reduces intracardiac interstitial fibrosis in the animal models
      of hypertensive heart failure and diabetic cardiomyopathy by inhibiting cardiac
      fibroblasts. The present study examined whether Tra has long-term effects on the
      cardiac remodeling in the remote area of the left ventricle (LV) following
      myocardial infarction (MI) in the rat. Treatment with Tra (n=40; 150 mg/kg twice
      daily) or placebo (Plac, n=36) was started at day 28 after induction of a large
      MI or sham-operation (ShO, n=18) in female Lewis rats. Collagen content was
      determined using high-performance liquid chromatography. Large MI led to a
      significant hypertrophy of the two ventricles, a severe dilatation of the LV and
      a shift of the chamber stiffness variables in the pressure volume curves. The six
      month survival rates were Tra, 62.5%; Plac, 75%; and ShO, 100%. No significant
      difference was identified between Tra and Plac regarding survival rate and
      collagen content. Treatment with the anti-inflammatory and antifibrotic drug,
      Tra, started four weeks after the induction of a large MI in the rat, did not
      attenuate or positively influence remodeling in chronic ischemic heart failure
      and survival. Further studies are required to explore the effects of Tra on
      cardiac myocytes post-MI in more detail.

PMID- 25371735
TI  - Neonatal incontinentia pigmenti: Six cases and a literature review.
AB  - The aim of this study was to retrospectively analyze the cases of six infants
      with incontinentia pigmenti (IP) in the Department of Neonates and compare their
      data with 60 cases of IP reported in the available Chinese literature, in order
      to determine the clinical characteristics and outcomes of neonatal IP in China.
      The majority of the cases were located near the eastern and southern coasts of
      China, and ~98.5% of IP cases occurred within 1 week of birth. The majority of
      the babies with IP were term infants. Twelve cases had a positive family history
      of IP. The mothers of 10 patients had a history of recurrent spontaneous
      abortions, and the mothers of five patients had infectious or autoimmune diseases
      during pregnancy. Cutaneous manifestations were shown at stage I in 59 cases, at
      stage II in 28 cases and at stage III in three cases (multiple stages were
      recorded in certain cases). Neurological changes occurred in 18 cases and ocular
      changes were observed in 12 cases. The toxoplasmosis, rubella, cytomegalovirus
      and herpes simplex (TORCH) test showed positive results in three cases;
      autoantibody positivity was found in three cases and high blood eosinophil levels
      were observed in 20 cases. Brain scans revealed positive results in 16 cases and
      complications were observed in 21 cases. Thirty-four cases were followed for 1-6
      months, six cases for 7-12 months and 17 cases for 13-84 months. Among these
      cases, 34 exhibited no evidence of recurrence. Five patients, including one male,
      succumbed in the long course of the follow-up. Two IP cases persisted after five
      years of follow-up. The data from the present study may reflect the
      characteristics of IP in the Chinese population and provide useful information
      for the diagnosis and treatment of IP by dermatologists and neonatologists.

PMID- 25371736
TI  - Application of high frequency color Doppler ultrasound in the monitoring of
      rheumatoid arthritis treatment.
AB  - The aim of the present study was to explore the use of high frequency color
      Doppler ultrasound to measure synovial thickness and blood flow to assess the
      therapeutic value of the recombinant human tumor necrosis factor (TNF) II
      receptor antibody fusion protein in rheumatoid arthritis (RA) treatment. A total
      of 36 clinically-diagnosed patients with RA were treated with methotrexate
      tablets or the recombinant TNF-receptor antibody fusion protein for 24 weeks.
      Joint synovial thickness and synovial blood flow integrity were monitored by high
      frequency color Doppler in the second metacarpophalangeal joint in one hand. The
      correlation of the erythrocyte sedimentation rate, C-reactive protein (CRP) and
      28-joint disease activity score (DAS28) with the ultrasound parameters were
      analyzed. Metacarpophalangeal second joint 2 (MCP2) synovial thickness, wrist
      joint synovial thickness and MCP2 synovial blood flow, prior and subsequent to
      the treatment, have a high correlation with DAS28 (P<0.05), and the MCP2 synovial
      blood flow integral has a strong correlation with CRP. Evaluating the wrist joint
      synovial thickness and synovial integrity of the second metacarpophalangeal joint
      using high frequency ultrasound detection can effectively evaluate the disease
      status in patients with RA. This procedure is potentially valuable as a means of
      evaluating the curative effects of RA treatments.

PMID- 25371737
TI  - Glypican 4 may be involved in the adipose tissue redistribution in high-fat
      feeding C57BL/6J mice with peroxisome proliferators-activated receptor gamma
      agonist rosiglitazone treatment.
AB  - Fat distribution affects the risk of developing obesity-related chronic diseases.
      Glypican 4 (Gpc4) may be involved in the regulation of obesity and body fat
      distribution. The aim of the study was to explore whether Gpc4 affects fat
      accumulation and the possible mechanism. C57BL/6J mice were fed with a high-fat
      diet for eight weeks and treated with a peroxisome proliferators-activated
      receptor gamma (PPARgamma) agonist, rosiglitazone, for another four weeks. The
      weight of inguinal and epididymal fat pads was determined. The Gpc4 mRNA and
      protein expression and two probable regulators of the Gpc4 gene, specificity
      protein 1 (Sp1) and Sp3 mRNA, were also measured. Mice treated with rosiglitazone
      showed a significant increase in subcutaneous fat weight compared with the
      untreated mice. The expression of Gpc4 mRNA and protein was significantly higher
      in visceral than in subcutaneous fat in all the groups. Compared with untreated
      mice the expression of Gpc4 and Sp3 mRNA in subcutaneous fat and the expression
      of Sp1 and Sp3 mRNA in visceral fat in mice treated with rosiglitazone increased
      significantly. The Sp3/Sp1 ratio was consistent with the expression of Gpc4 mRNA
      and protein in subcutaneous and visceral fat. The present study indicated that
      Gpc4 may play an important role in fat distribution, and this effect is perhaps
      regulated by the ratio of Sp3/Sp1 in the subcutaneous and visceral fat tissues.

PMID- 25371738
TI  - Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute
      lung injury induced by severe acute pancreatitis in rats via the upregulation of
      aquaporin-1.
AB  - Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water
      transport; thus, AQP-1 plays an important role in a number of edema-associated
      lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been
      shown to effectively reduce the mortality rate of acute lung injury (ALI) induced
      by severe acute pancreatitis (SAP). The current study aimed to investigate the
      detailed mechanisms underlying the effects of QYT on ALI induced by SAP,
      particularly the effects on the expression levels of AQP-1 in the lung tissue.
      ALI was established in Wister rats who were subsequently divided into four
      groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT
      group, 20 ml/kg QYT was administered by gavage immediately following the
      induction of SAP. Blood and lung tissues were collected 8 h following the
      induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood
      gases, serum amylase and tumor necrosis factor-alpha (TNF-alpha), were measured
      at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression
      levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain
      reaction, immunohistochemistry and western blot analysis. No statistically
      significant differences were observed with regard to the levels of serum amylase,
      wet/dry ratio, partial pressure of oxygen, serum TNF-alpha and pathological
      changes in the pulmonary tissue between the QYT and DEX groups; however, a
      statistically significant difference was observed when compared with the ALI
      group. The expression levels of AQP-1 significantly increased (P<0.05) and lung
      edema was alleviated in the QYT and DEX groups, when compared with ALI group.
      Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT
      protects the lungs from injury induced by SAP via the upregulation of AQP-1,
      which suppresses TNF-alpha expression.

PMID- 25371739
TI  - Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV
      negative immunocompromised patients with Pneumocystis pneumonia.
AB  - The purpose of this study was to investigate dihydropteroate synthase (DHPS)
      mutations and their clinical context in non-HIV-infected patients with
      Pneumocystis pneumonia (PCP). DHPS genes in respiratory samples collected from
      HIV-negative patients with PCP presented between January 2008 and April 2011 were
      amplified by polymerase chain reaction (PCR) and sequenced. Basic clinical data
      from the medical records of the patients were also reviewed. The most common
      point mutations, which result in Thr55Ala and Pro57Ser amino acid substitutions,
      were not detected in the Pneumocystis jirovecii sampled from the HIV-negative
      patients. Two other point mutations, which result in nonsynonymous mutation,
      Asp90Asn and Glu98Lys, were identified in P. jirovecii from two patients. Among
      the patients, the levels of lactate dehydrogenase (LDH), C-reactive protein (CRP)
      and plasma (1-3) beta-D-glucan were elevated in 75, 92.31 and 42.86% of patients,
      respectively. The percentage of circulating lymphocytes was significantly lower
      in non-survivors than in survivors [4.2%, interquartile range (IQR) 2.4-5.85
      versus 10.1%, IQR 5.65-23.4; P=0.019]. The neutrophil proportion in
      bronchoalveolar lavage fluid (BALF) was significantly higher in non-survivors
      than in survivors (49.78+/-27.67 versus 21.33+/-15.03%; P=0.047). Thirteen
      patients had received adjunctive corticosteroids (1 mg/kg/day prednisone
      equivalent) and nine (69.23%) of them eventually experienced treatment failure.
      No common DHPS gene mutations of P. jirovecii were detected in the HIV-negative
      PCP patients. However, other mutations did exist, the significance of which
      remains to be further identified. The elevation of neutrophil counts in BALF and
      reduction of the number of lymphocytes in peripheral blood may be associated with
      poor outcome. The efficacy of adjunctive steroid therapy in HIV-negative patients
      with P. jirovecii infection requires further investigation.

PMID- 25371740
TI  - Incidental esophageal submucosal tumor detection by chest radiography: A case
      report.
AB  - Esophageal submucosal tumors are occasionally detected incidentally during a
      gastrointestinal survey. In the present study, a case of esophageal leiomyoma is
      reported, which was incidentally detected by chest radiography during an annual
      survey of mass-screening for lung cancer. The patient underwent a laparoscopic
      lower esophagectomy, a proximal gastrectomy and a gastric tube reconstruction.
      Macroscopic examination revealed a 50*40*28-mm mass, while microscopic
      examination identified submucosal smooth muscle tissue without mitotic activity
      or necrosis. The tumor was diagnosed as an esophageal leiomyoma. The patient was
      asymptomatic during the three-month follow-up period. However, when a mass lesion
      adjacent to the gastrointestinal tract is detected during chest radiography, the
      possibility of a rare disease should be considered. Therefore, further
      investigation with upper gastrointestinal radiography and gastroendoscopy should
      be performed.

PMID- 25371741
TI  - A nutrient mixture reduces the expression of matrix metalloproteinases in an
      animal model of spinal cord injury by modulating matrix metalloproteinase-2 and
      matrix metalloproteinase-9 promoter activities.
AB  - This study aimed to determine whether a novel nutrient mixture (NM), composed of
      lysine, ascorbic acid, proline, green tea extracts and other micronutrients,
      attenuates impairments induced by spinal cord injury (SCI) and to investigate the
      related molecular mechanisms. A mouse model of SCI was established. Thirty-two
      mice were divided into four groups. The sham group received vehicle only. The SCI
      groups were treated orally with saline (saline group), a low dose (500 MUg 3
      times/day) of NM (NM-LD group) or a high dose (2,000 MUg 3 times/day) of NM (NM
      HD group). The levels of mouse hindlimb movement were determined every day in the
      first week post-surgery. The protein expression levels of matrix
      metalloproteinase (MMP)-2 and MMP-9 were determined by western blotting. Wild
      type and mutant MMP-2- and MMP-9-directed luciferase constructs were generated
      and their luciferase activities were determined. NM significantly facilitated the
      recovery of hindlimb movement of the mice in comparison to that in the saline
      group. The expression levels of MMP-2 in the NM-LD and NM-HD groups were
      decreased by ~50% compared with the saline group as indicated by western blotting
      results. The expression levels of MMP-9 in the NM-LD and NM-HD groups were
      decreased to ~25 and ~10%, respectively. These results suggest that NM
      significantly inhibits the expression of MMP-2 and MMP-9 proteins. Reverse
      transcription quantitative polymerase chain reaction results indicated that NM
      reduced the levels of MMP-2 and MMP-9 mRNA. Furthermore, the luciferase results
      indicated that site-directed mutagenesis comprising a -1306 C to T (C/T) base
      change in the MMP-2 promoter and a -1562 C/T base change in the MMP-9 promoter
      abolished the inhibitory effects of NM on MMP-2 and MMP-9 promoters. These
      results suggest that NM attenuates SCI-induced impairments in mice movement by
      negatively affecting the promoter activity of MMP-2 and MMP-9 genes and thus
      decreasing the expression of MMP-2 and MMP-9 proteins.

PMID- 25371742
TI  - Lactobacillus plantarum NDC 75017 alleviates the learning and memory ability in
      aging rats by reducing mitochondrial dysfunction.
AB  - The aim of the present study was to investigate the protective effect of
      Lactobacillus plantarum NDC 75017 on D-galactose (D-gal)-induced mitochondrial
      dysfunction in the rat cerebral cortex. Fifty rats were randomly divided into
      five groups (n=10 in each group). The rats in the aging model group were
      subcutaneously injected with 100 mg/kg D-gal and those in the protective groups
      were additionally orally administered L. plantarum NDC 75017 at doses of 1*108,
      1*109 or 1*1010 CFU/100 mg body weight/day, respectively. The control rats were
      administrated an equal volume of the vehicle. Following continuous treatment for
      seven weeks, the learning and memory abilities and mitochondrial ultrastructure,
      function and adenosine triphosphate (ATP) levels were examined. The results
      showed that the learning and memory abilities and mitochondrial levels of ATP
      were significantly decreased in the D-gal-induced aging model group compared with
      those in the control group (P<0.01). In addition, marked changes in the
      mitochondrial functions and ultrastructure were observed between the groups.
      Seven weeks of L. plantarum NDC 75017 and D-gal coadministration significantly
      improved the learning and memory abilities of the rats compared with the D-gal
      induced aging model group. Furthermore, the combination regime significantly
      improved the mitochondrial ultrastructure and functions, including the
      mitochondrial respiratory chain, mitochondrial membrane potential and
      mitochondrial permeability transition. The results revealed that the L. plantarum
      NDC 75017 was able to alleviate learning and memory injuries in aging rats by
      reducing the mitochondrial dysfunction induced by D-gal.

PMID- 25371743
TI  - Laxative effects of fermented rice extract in rats with loperamide-induced
      constipation.
AB  - Constipation is a common problem in males and females. The aim of the present
      study was to evaluate the laxative effects of fermented rice extract (FRe) on
      rats with loperamide-induced constipation. FRe (100, 200 and 300 mg/kg) was
      administered orally once per day for six days following 1 h loperamide treatment.
      The laxative effects of FRe were compared with those of sodium picosulfate (S.
      picosulfate). Following the induction of constipation in the rats, a marked
      decrease was observed in the fecal pellet number and water content discharged
      over 24 h, the surface mucus thickness in the colonic lumen, intestinal charcoal
      transit ratio, thickness of the colonic mucosa and the number of mucus-producing
      cells, while an increase was observed in the number of fecal pellets remaining in
      the colonic lumen and their mean diameter, as compared with the normal vehicle
      control rats. These conditions were significantly alleviated following the
      administration of the three doses of FRe when compared with the loperamide
      control group. However, the alleviating effects were lower than those of S.
      picosulfate, with the exception of the intestinal charcoal transit ratio. Similar
      effects on the intestinal charcoal transit ratio were detected for the three
      doses of FRe when compared with the S. picosulfate-treated rats. In conclusion,
      the results indicated that FRe exhibits a laxative effect without causing
      diarrhea, as compared with sodium picosulfate; thus, FRe may be effective as a
      complementary medicine in patients suffering from lifestyle-induced constipation.

PMID- 25371744
TI  - Cetrotide administration in the early luteal phase in patients at high risk of
      ovarian hyperstimulation syndrome: A controlled clinical study.
AB  - The aim of the present pilot study was to assess the feasibility and efficacy of
      Cetrotide administration in the early luteal phase in patients at high risk of
      ovarian hyperstimulation syndrome (OHSS), undergoing embryo cryopreservation
      following superovulation. A total of 135 patients at high risk of OHSS and
      undergoing embryo cryopreservation were divided into two groups. In the treatment
      group (n=39), the patients received daily subcutaneous injections of 0.25 mg
      Cetrotide between days 1 and 5 following ooctye retrieval, and volume expansion
      and symptomatic treatment were also provided. In the control group (n=96), the
      patients received routine treatments, including volume expansion therapy. The
      serum steroid hormone concentrations of the patients were measured on days 2, 5
      and 8 following ooctye retrieval, while the incidence of moderate or severe OHSS,
      self-evaluated clinical symptoms and various clinical indicators were recorded.
      The serum estradiol (E2), luteinizing hormone and progesterone levels in the
      treatment group on days 2, 5 and 8 following oocyte retrieval were not found to
      differ significantly when compared with the patients in the control group
      (P>0.05). The incidence of severe OHSS did not differ significantly between the
      two groups (P>0.05). The average length of hospital stay and length of luteal
      phase were not found to be significantly different between the treatment and
      control groups (P>0.05). In conclusion, Cetrotide injections in the early luteal
      phase did not alter the serum steroid levels of patients at high risk of OHSS
      undergoing embryo cryopreservation, and were unable to reduce the incidence of
      severe early OHSS. However, further randomized studies are required to evaluate
      the effectiveness of Cetrotide in the prevention of OHSS.

PMID- 25371745
TI  - Levels of acylation stimulating protein and the complement component 3 precursor
      are associated with the occurrence and development of coronary heart disease.
AB  - The aim of the present study was to investigate whether acylation stimulating
      protein (ASP) and complement component 3 (C3) are associated with the occurrence
      and development of coronary heart disease (CHD). The participants of the study
      were divided into three groups, including the healthy control (n=42), metabolic
      syndrome (MS, n=56) and CHD (n=62) groups. An enzyme-linked immunosorbent assay
      was used to measure the ASP concentrations, while an immunoturbidimetric assay
      was employed to determine the C3 concentrations. In addition, coronary
      angiography was performed to determine the severity of coronary artery disease in
      the CHD group. The CHD group was divided into three subgroups, according to the
      final Gensini score of coronary artery stenosis for each patient (mild, <=20
      points; moderate, 21-40 points; severe, >40 points). Western blotting and
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) were
      performed to analyze the protein and mRNA expression levels of C3 in the CHD
      subgroups and the healthy control group. The concentrations of ASP and C3 in the
      CHD group were found to be significantly higher compared with the control and MS
      groups. In addition, the levels of ASP and C3 in the mild and moderate CHD
      subgroups were significantly higher compared with the healthy controls or mild
      CHD patients. Furthermore, the protein expression levels of C3 in the moderate
      and severe CHD patients were found to be significantly higher compared with the
      healthy individuals and the mild CHD patients. The quantitative RT-PCR results
      revealed that the mRNA expression levels of C3 in the moderate and severe CHD
      patients were significantly higher compared with the healthy control group and
      the mild CHD patients. Furthermore, the mean levels of C3 transcripts in the
      severe CHD patients were found to be higher compared with the moderate CHD
      subgroup (P<0.05). Therefore, ASP and C3 were found to be associated with the
      occurrence and development of CHD; thus, may be used as novel indexes for CHD.

PMID- 25371746
TI  - Association between diabetes mellitus with metabolic syndrome and diabetic
      microangiopathy.
AB  - The aim of this study was to investigate the association between diabetes
      mellitus (DM), mainly type II, with metabolic syndrome (MS) and diabetic
      nephropathy (DN)/diabetic retinopathy (DR). Based on the analysis of the
      prevalence of MS, patients with DM were divided into MS and non-MS groups
      according to the presence or absence of MS. The correlation between DN, DR and
      certain factors, including gender, age, disease duration and the presence or
      absence of a family history of MS, were analyzed. The prevalence of MS among the
      patients with DM was 62.50%. The prevalence of DN was 55.33% in the MS group and
      that of DR was 26.00%. DN was positively correlated with age, gender, blood
      pressure, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and
      blood uric acid. DR was positively correlated with traceable disease duration and
      LDL-C. In conclusion, DM occurred more frequently in concurrence with MS than
      without MS, and the prevalence of DN/DR in the MS group was higher than that in
      the non-MS group. Age, gender, blood pressure, TG, LDL-C and blood uric acid were
      risk factors for DN and the traceable disease duration and LDL-C were risk
      factors for DR.

PMID- 25371747
TI  - Tuberculosis preventive treatment in a single medical center and evaluation of
      the results.
AB  - The aim of the present study was to evaluate the application of tuberculosis
      preventive treatment (TB-PT). Demographic data, indications and results for cases
      that received TB-PT at the Ankara Tuberculosis Control Dispensary No. 7 between
      2008 and 2011 were retrospectively evaluated. The 'Prevention with Drugs'
      registry at the dispensary was used. A total of 463 cases received TB-PT, with
      the indications including close contact with an active TB case (44%), positive
      tuberculin skin test (TST) in a child <15 years-old (25%) and immunosuppressive
      therapy (31%). The immunosuppressed group (n=144) were administered steroids
      (10%) or tumor necrosis factor (TNF)-alpha inhibitors (90%). Indications of TST
      conversion and sequela lesions were not observed among the cases. The male/female
      ratio was 106/98 for cases with TB close contact, 61/54 for TST-positive cases
      and 85/59 for immunosuppressed cases. The mean ages of these groups were 9+/-5.7,
      9.5+/-3.8 and 38+/-14.9 years, respectively. TB-PT was completed in 364 cases
      (78.6%), and the rate of discontinuation due to adverse effects was 1% for TB
      close contact and 2% for TST-positive cases, but 5% for immunosuppressed cases.
      While the percentage of TB close contact cases receiving TB-PT decreased during
      the four-year study period, the percentage of cases with immunosuppression (in
      particular patients using TNF-alpha inhibitors) increased. Among the studied
      cases, only two subjects developed active TB. The first case involved a 1.5-year
      old female that had close contact exposure to TB from a parent, while the other
      case involved a 14-year-old TST-positive male (induration size,16 mm). In
      conclusion, patients receiving TB-PT should be monitored and/or followed-up
      carefully to control any side-effects from the treatment and development of
      active TB.

PMID- 25371748
TI  - MicroRNA-185 inhibits proliferation by targeting c-Met in human breast cancer
      cells.
AB  - MicroRNAs (miRNAs) are a group of small non-coding RNA molecules that have been
      shown to regulate the expression of genes involved in tumorigenesis. The
      relevance of miRNAs in the development, progression and prognosis of human breast
      cancer is not fully understood. miR-185 has been demonstrated to be involved in
      the pathogenesis of several types of cancers; however, its role in breast cancer
      has not yet been elucidated. In the present study, the expression of miR-185 was
      analyzed by quantitative polymerase chain reaction. In addition, an MTT assay and
      flow cytometry were used to determine the rates of cell proliferation and
      apoptosis. Protein expression was analyzed by western blotting and the target
      gene was confirmed using a luciferase reporter assay. The expression of miR-185
      was found to be downregulated in the breast cancer tissues. The MTT assay
      revealed that overexpression of miR-185 inhibited the proliferation of MDF7 and
      SKBR3 cells. Furthermore, flow cytometric analysis demonstrated that increased
      expression levels of miR-185 promoted the apoptosis of breast cancer cells. In
      addition, c-Met expression was demonstrated to be significantly upregulated in
      breast cancer tissues and cells, and the c-Met gene was identified to be a target
      of miR-185. Therefore, the results demonstrated that miR-185 inhibited the
      proliferation of breast cancer cells by regulating the expression of c-Met,
      indicating its potential as a therapeutic target for breast cancer.

PMID- 25371749
TI  - Effect of rabeprazole on the transport and distribution of levofloxacin in rat
      stomachs.
AB  - The aim of this study was to determine the transport and distribution
      characteristics of levofloxacin in the rat stomach and investigate the effects of
      combination treatment with rabeprazole. A total of 160 Wistar rats were randomly
      divided into four treatment groups: 50 mg/kg levofloxacin, 100 mg/kg
      levofloxacin, 50 mg/kg levofloxacin + rabeprazole and 100 mg/kg levofloxacin +
      rabeprazole. For two hours after intravenous administration, serum, gastric juice
      and stomach mucosa samples were collected at 15-min intervals, and the
      levofloxacin concentrations in all the samples were measured to determine the
      transport and distribution characteristics of levofloxacin in the rat stomach. In
      the 50 mg/kg levofloxacin and the 100 mg/kg levofloxacin groups, the drug
      concentration in the gastric juice gradually exceeded the serum concentration
      within 45-60 min of administration (P<0.05) and the drug concentrations in the
      gastric body and antrum were higher than those in the serum and the forestomach
      (P<0.05). At 15-30 min after administration, the drug concentrations in the
      gastric juice in the 50 mg/kg levofloxacin + rabeprazole and the 100 mg/kg
      levofloxacin + rabeprazole groups gradually exceeded the serum concentration
      (P<0.05). However, the levofloxacin concentration in the gastric body and in the
      antrum did not significantly differ between the two groups (P>0.05). The
      levofloxacin concentrations in each stomach region in the groups also treated
      with rabeprazole were higher than those treated with levofloxacin alone, but the
      differences were not significant. The levofloxacin transport fractions in the
      stomach in the 50 mg/kg levofloxacin, 100 mg/kg levofloxacin, 50 mg/kg
      levofloxacin + rabeprazole and 100 mg/kg levofloxacin + rabeprazole groups were
      2.36, 2.52, 2.42 and 2.55, respectively, and no significant difference was
      identified. Levofloxacin may be actively transported in the rat stomach. The
      levofloxacin concentration in the gastric antrum exceeded that in the
      forestomach, and the local concentration increased with increasing dosage.
      Combining a proton pump inhibitor with levofloxacin has little effect on the
      concentration and distribution of levofloxacin in the stomach within 2 h.

PMID- 25371750
TI  - Brain-derived neurotrophic factor exerts neuroprotective actions against amyloid
      beta-induced apoptosis in neuroblastoma cells.
AB  - Alzheimer's disease (AD) brains demonstrate decreased levels of brain-derived
      neurotrophic factor (BDNF) and increased levels of beta-amyloid peptide (Abeta),
      which is neurotoxic. The present study assessed the impact of BDNF on the toxic
      effects of Abeta25-35-induced apoptosis and the effects on BDNF-mediated
      signaling using the MTT assay, western blotting and reverse transcription
      quantitative polymerase chain reaction. Abeta25-35 was found to induce an
      apoptosis, dose-dependent effect on SH-SY5Y neuroblastoma cells, which peaked at
      a concentration of 20 MUM after 24 h. A combination of Abeta25-35 and BDNF
      treatment increased the levels of Akt and decreased the level of glycogen
      synthase kinase-3beta (GSK3beta) in SH-SY5Y neuroblastoma cells. These findings
      indicated that BDNF administration exerted a neuroprotective effect against the
      toxicity of the Abeta25-35-induced apoptosis in these cells, which was
      accompanied by phosphoinositide 3-kinase/Akt activation and GSK3beta
      phosphorylation. The mechanisms and signaling pathways underlying neuronal
      degeneration induced by the Abeta peptide remain to be further elucidated.

PMID- 25371751
TI  - Toll-like receptor-4 pathway is required for the pathogenesis of human chronic
      endometritis.
AB  - Toll-like receptor (TLR) signal transduction is a central component of the
      primary innate immune response to pathogenic challenge. TLR4, a member of the TLR
      family, is highly expressed in the endometrial cells of the uterus and could thus
      be a key link between human chronic endometritis (CE) and the immune system.
      However, the exact biological function of TLR4 in human CE remains largely
      unexplored. The present study aimed to examine the role of TLR4 in human CE. A
      comprehensive expression and activation analysis of TLR4 in the endometrial cells
      of the uterus from patients with human CE (n=25) and normal endometrial (NE)
      tissue (n=15) was performed. Western blot analyses demonstrated that compared
      with NE, the protein expression TLR4 markedly increased in human CE. Endometrial
      tissue scrapings were also used for total RNA extraction and were transcribed and
      amplified by reverse transcription quantitative polymerase chain reaction. The
      results showed that significant upregulation of tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1beta (IL-1beta), and downregulation of IL-10 mRNA was
      observed in CE compared with the NE group. Furthermore, the protein of the
      signaling adapter myeloid differentiation factor-88 and the accessory molecules
      (TNF receptor associated factor 6 and transforming growth factor-beta-activated
      kinase 1) were also detected in all the assayed tissues. Of note, differential
      expression (CE versus NE) was observed by immunoblotting at each level of the
      nuclear factor-kappaB signaling cascade, including inhibitor kappaBalpha and P65
      (all P<0.05). The altered TLR4 and its corresponding downstream signaling
      molecules in CE cells may be of relevance for the progression of the human CE.
      These findings indicate that the evaluation of expression patterns of TLR4 holds
      promise for the treatment of human CE.

PMID- 25371752
TI  - microRNA-18a is a genetic marker for the early diagnosis of cerebral injury
      induced by type 2 diabetes.
AB  - The present study aimed to investigate the value of microRNA (miRNA)-18a for the
      early diagnosis of cerebral injury in patients with type 2 diabetes. Blood
      samples were collected from patients with type 2 diabetes, admitted to hospital
      between January and December 2013. The patients were randomly divided into three
      groups, which included one control and two experimental groups of severely and
      mildly diabetic patients (33 individuals per group). The levels of biochemical
      indicators in the serum, including S100 protein, neuron-specific enolase, myelin
      basic protein and endothelin-1, were determined. The mRNA and protein expression
      levels of hypoxia-inducible factor (HIF)-1alpha in the serum were measured by
      quantitative polymerase chain reaction (qPCR) and western blot analysis,
      respectively. In addition, the serum expression levels of miRNA-18a were
      determined by qPCR. The concentrations of the biochemical indicators in the
      severe diabetes group were significantly higher compared with those from the
      other two groups. Furthermore, the mRNA and protein expression levels of HIF
      1alpha in the severe diabetes group were significantly upregulated compared with
      the other groups. However, the levels of miRNA-18a in the severe diabetes group
      were significantly downregulated compared with the other groups. The present
      study demonstrated that the elevation of biochemical indicators in the serum and
      the upregulation of HIF-1alpha mRNA and protein expression are associated with
      the downregulation of miRNA-18a. Therefore, miRNA-18a may be a potential genetic
      marker for the early diagnosis of cerebral injury induced by type 2 diabetes.

PMID- 25371753
TI  - Levels of circulating TNF-related apoptosis-inducing ligand in celiac disease.
AB  - It has previously been demonstrated that the circulating levels of TNF-related
      apoptosis-inducing ligand (TRAIL) are significantly lower in patients with type 1
      diabetes (T1D) than in normal age- and gender-matched controls. Since celiac
      disease (CD) is often associated with T1D, a retrospective study was performed to
      analyze the sera of a cohort of pediatric subjects: i) patients with CD at onset
      (n=100); ii) patients with potential CD (n=45); iii) patients with CD associated
      with other auto-immune diseases (n=17); and iv) patients with eosinophilic
      esophagitis (n=15). Among the patients with CD, 49 were also analyzed after six
      months on a gluten-free diet, while data were also available for 13 patients
      after one year on a gluten-free diet. No significant differences were found in
      the circulating levels of TRAIL between the patients with CD and the patients
      with either eosinophilic esophagitis or potential CD. Patients with CD associated
      with other auto-immune diseases showed significantly lower levels of TRAIL when
      compared with patients with CD alone. The gluten-free diet did not significantly
      modify the levels of circulating TRAIL at 6 or 12 months. Thus, although T1D and
      CD share common immunological features, the circulating levels of TRAIL show a
      significant difference between the two pathologies, and do not appear to be
      modulated in CD.

PMID- 25371754
TI  - Tumor necrosis factor-alpha promotes the expression of excitatory amino-acid
      transporter 2 in astrocytes: Optimal concentration and incubation time.
AB  - The aim of the present study was to determine whether tumor necrosis factor (TNF)
      alpha regulates the expression levels of excitatory amino-acid transporters
      (EAATs) in primary astrocytes and its roles in brain ischemia. Exogenous TNF
      alpha was administered to pure cultured astrocytes and the expression levels of
      EAAT1, EAAT2 and glial fibrillary acidic protein (GFAP) were evaluated. The
      results showed that TNF-alpha at 10 ng/ml enhanced the expression of EAAT2 in a
      time-dependent manner, while the expression levels of EAAT1 and GFAP did not
      change. To determine whether the elevation in the levels of the EAAT2 protein
      induced by TNF-alpha had a beneficial effect on ischemic insult, TNF-alpha was
      applied to in vitro models of cerebral ischemia; the treatment was observed to
      increase neuronal viability. The present results suggest that a relatively short
      term application of an optimal concentration of TNF-alpha may protect neurons
      against ischemic injury by elevating the expression of EAAT2 in astrocytes.

PMID- 25371755
TI  - Toll-like receptor 4 agonist, lipopolysaccharide, increases the expression levels
      of cytokines and chemokines in human peripheral blood mononuclear cells.
AB  - Toll-like receptors (TLRs) are members of the pattern recognition receptor family
      and are essential in the innate immune response. In total, 11 TLRs exist in
      humans, which are expressed in a variety of cells, including peripheral blood
      cells. TLR4 plays a significant role in the defense against gram-negative
      pathogens by recognizing the lipopolysaccharide (LPS) molecules in these
      bacteria. The aim of the present study was to detect the expression level
      variation of a number of major immune molecules in peripheral blood mononuclear
      cells (PBMCs) stimulated by LPS, in order to identify candidate genes involved in
      the biological functions mediated by TLR4. Reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) analysis and an antibody chip were performed
      in the current study. The RT-qPCR results revealed a marked enhancement in the
      expression levels of various molecules, including cytokines, chemokines, growth
      factors and protein kinases. In addition, the antibody chip identified the
      increased secretion of crucial proinflammatory molecules in the supernatants
      collected from LPS-treated PBMCs. In conclusion, a large number of molecules were
      found to be involved in TLR4-mediated functions.

PMID- 25371756
TI  - Blood-patch pleurodesis for pneumothorax in lung fibrosis due to progressive
      systemic sclerosis: A case report.
AB  - Pneumothorax in patients with progressive systemic sclerosis (PSS) often presents
      as a difficult-to-treat disease. Autologous blood-patch pleurodesis has
      previously been used for the treatment of pneumothorax. Blood outside its own
      environment is an irritant; therefore, chest physicians must watch closely for an
      allergic reaction. The injection is simple, painless, causes no side effects, is
      an inexpensive treatment for pneumothorax and is available not only in patients
      with persistent air leak but also in those with residual air space. A case is
      reported here of blood-patch pleurodesis for pneumothorax in lung fibrosis due to
      PSS. As an alternative therapy for difficult-to-treat pneumothorax in patients
      with PSS with persistent air leak and residual air space, autologous blood-patch
      pleurodesis would be one of the treatment options.

PMID- 25371757
TI  - Analysis of ventilator-associated pneumonia infection route by genome
      macrorestriction-pulsed-field gel electrophoresis and its prevention with
      combined nursing strategies.
AB  - The aim of the present study was to explore the infection route of ventilator
      associated pneumonia (VAP) and assess the effectiveness of a combined nursing
      strategy to prevent VAP in intensive care units. Bacteria from the gastric juice
      and drainage from the hypolarynx and lower respiratory tracts of patients with
      VAP were analyzed using genome macrorestriction-pulsed-field gel electrophoresis
      (GM-PFGE). A total of 124 patients with tracheal intubation were placed in the
      intervention group and were treated with a combined nursing strategy, comprising
      mosapride (gastric motility stimulant) administration and semi-reclining
      positioning. A total of 112 intubated patients were placed in the control group
      and received routine nursing care. The incidence rate of VAP, days of ventilation
      and mortality rate of patients were compared between the two groups. The GM-PFGE
      fingerprinting results of three strains of Pseudomonas aeruginosa from the
      gastric juice, subglottic secretion drainage and drainage of the lower
      respiratory tract in patients with VAP were similar across groups. The number of
      days spent on a ventilator by patients in the intervention group (7.37+/-5.32
      days) was lower compared with that by patients in the control group (12.34+/-4.98
      days) (P<0.05). The incidence rate of VAP was reduced from 40.81 to 21.25%
      following intervention with the combined nursing strategy (P<0.05); furthermore,
      the mortality rate of intubated patients in the intervention group was 29.46%, a
      significant reduction compared with the 41.94% mortality rate observed in the
      control group (P<0.05). Gastroesophageal reflux (GER) was confirmed as one of the
      infection routes for VAP. The combined nursing strategy of gastric motility
      stimulant administration and the adoption of a semi-reclining position was
      effective in preventing VAP by reducing the occurrence of GER.

PMID- 25371758
TI  - Lymphomatoid papulosis misdiagnosed as pityriasis lichenoides et varioliformis
      acuta: Two case reports and a literature review.
AB  - The aim of this study was to improve the level of diagnosis and differential
      diagnosis of lymphomatoid papulosis (LyP). Two cases of type B LyP were
      identified and the literature was reviewed to summarize the clinical outcomes and
      pathology of LyP and its treatment. The two patients exhibited symptoms with
      papulonodular lesions, the centers of which gradually underwent ulceration and
      necrosis. CD30, a helper T-cell marker specifically expressed in tumor cells was
      analyzed by immunohistochemical staining and the result showed that CD30-negative
      or only scattered CD30-positive cells were present. Therefore, a diagnosis of
      type B LyP was made. A fairly good curative effect was achieved following
      treatment with retinoic acid, glucocorticoids and immunomodulatory drugs. LyP is
      a type of low-level malignant lymphoma and is easily misdiagnosed as pityriasis
      lichenoides et varioliformis acuta and other diseases. In order to avoid under
      diagnosis and misdiagnosis, doctors should evaluate suspected patients by
      histopathological and immunohistochemical examination.

PMID- 25371759
TI  - Superiority of the modified Tonnis angle over the Tonnis angle in the
      radiographic diagnosis of acetabular dysplasia.
AB  - The aim of this study was to evaluate the limitations of the Tonnis angle as one
      of the most commonly used parameters in the diagnosis of acetabular dysplasia,
      and to explore the feasibility of the modified Tonnis angle in the diagnosis of
      acetabular dysplasia. A total of 224 patients (120 females and 104 males) with
      448 hips, aged between 15 and 83 years (median, 45.0 years), were selected for
      the measurement of the center-edge (CE) and Tonnis angles. To evaluate the
      relative position of the medial edge of the acetabular sourcil, a new parameter,
      known as the center-medial-edge (CME) angle, was designed. As an improvement of
      the Tonnis angle, a new angle preliminarily termed the modified Tonnis angle was
      created. In addition, the degree of clarity of the medial edge of the acetabular
      sourcil on radiograph was evaluated, and the hips were divided into the clear
      edge and blurred-edge groups. The hips belonging to the blurred-edge group could
      not be used for Tonnis angle measurements. All measurements were performed
      digitally using the tool of the picture-archiving communication system. Among the
      448 acetabular sourcils, 142 had a blurred medial edge (31.7%). The mean value of
      the CME angle was 37.94 degrees , with a range of 21.76-63.99 degrees . The 95%
      prediction interval of the modified Tonnis angle was estimated to be -6.39 to
      11.73 degrees . The correlation coefficients were -0.838 between the CE and
      Tonnis angles, 0.889 between the Tonnis and modified Tonnis angles and -0.905
      between the CE and modified Tonnis angles. In conclusion, the modified Tonnis
      angle can substitute for the Tonnis angle without joint space narrowing and
      subluxation of the hip, particularly when the Tonnis angle cannot be measured due
      to a blurred medial edge of the acetabular sourcil on pelvic radiograph.

PMID- 25371760
TI  - Protective effects of N-acetylcysteine on cisplatin-induced oxidative stress and
      DNA damage in HepG2 cells.
AB  - Hepatocyte injury is a common pathological effect of cisplatin (CDDP) in various
      solid tumor therapies. Thus, strategies for minimizing CDDP toxicity are of great
      clinical interest. N-acetylcysteine (NAC), a known antioxidant, is often used as
      an antidote for acetaminophen overdose in the clinic due to its ability to
      increase the levels of glutathione (GSH). In the present study, the aim was to
      investigate the protective effects of NAC against CDDP-induced apoptosis in human
      derived HepG2 cells. The results showed that upon exposure of the cells to CDDP,
      oxidative stress was significantly induced. DNA damage caused by CDDP was
      associated with cell apoptosis. NAC pre-treatment significantly reduced the
      malondialdehyde (MDA) levels and ameliorated the GSH modulation induced by CDDP.
      NAC also protected against DNA damage and cell apoptosis. These data suggest the
      protective role of NAC against hepatocyte apoptosis induced by CDDP was achieved
      through the inhibition of DNA damage and alterations of the redox status in human
      derived HepG2 cells. These results indicate that NAC administration may protect
      against CDDP-induced damage.

PMID- 25371761
TI  - Infusion of allogeneic umbilical cord blood hematopoietic stem cells in patients
      with chemotherapy-related myelosuppression.
AB  - Chemotherapy-induced myelosuppression is one of the main problems in the
      treatment of cancer. In the present study, the effects of allogeneic umbilical
      cord blood hematopoietic stem cell (UCB-HSC) infusion were investigated on the
      treatment of chemotherapy-related myelosuppression. In total, 65 patients (male,
      42; female, 23) diagnosed with chemotherapy-related myelosuppression were
      included in the study. The majority of the patients were classified with stage II
      myelosupression at enrolment, and an average concentration of 7.07*109/l UCB-HSCs
      were transfused through the peripheral vein. The minimum values of the white
      blood cell (WBC) count, hemoglobin (Hb) level, platelet (PLT) count and Karnofsky
      performance status (KPS) scores were recorded prior to and between days 7 and 14
      following UCB-HSC infusion. When assessing the overall data, the results revealed
      that the mean WBC and PLT counts increased significantly following UCB-HSC
      infusion. However, the subgroup analyses based on gender and KPS score revealed
      that UCB-HSC infusion was more successful in male patients and those with a
      higher KPS score. Spearman's correlation analysis revealed a linear correlation
      between the number of transfused UCB-HSCs and the changes in the WBC and PLT
      counts following treatment. In conclusion, the results indicated that peripheral
      vein infusion of non-human leukocyte antigen matched UCB-HSCs can markedly
      improve chemotherapy-related myelosuppression in a safe and effective manner.

PMID- 25371762
TI  - Level and significance of plasma myeloperoxidase and the neutrophil to lymphocyte
      ratio in patients with coronary artery disease.
AB  - Inflammation plays a pivotal role in the etiology of coronary artery disease
      (CAD). Myeloperoxidase (MPO) is a potent inflammatory factor and a critical
      modulator of coronary inflammation and oxidative stress. The goal of this study
      was to determine the impact of the plasma MPO (pMPO) level and
      neutrophil/lymphocyte ratio on the clinical characteristics and outcomes of
      patients with CAD. Blood samples were collected from 210 patients with underlying
      chest pain or recent myocardial infarction (MI) prior to coronary angiography in
      order to measure pMPO levels. The pMPO levels and neutrophil/lymphocyte ratio
      were correlated with clinical characteristics and outcomes following
      catheterization. The pMPO level and neutrophil/lymphocyte ratio were higher in
      patients with recent MI than in patients with CAD (coronary occlusion >=50%) or
      without CAD (coronary occlusion <50%). Patients with ST segment elevated MI
      (STEMI) had a higher neutrophil/lymphocyte ratio relative to patients with non
      STEMI. The pMPO level was identified to correlate with the neutrophil/lymphocyte
      ratio and the need for coronary artery reperfusion by coronary artery bypass
      surgery or percutaneous coronary intervention. Patients who were taking aspirin
      had lower pMPO levels and neutrophil/lymphocyte ratio compared with those who
      were not taking aspirin. The plasma neutrophil/lymphocyte ratio was negatively
      associated with the left ventricular ejection fraction at baseline and the 30-day
      follow-up, whereas pMPO showed no correlation. Multivariate analysis indicated
      that the pMPO level was positively associated with MI, the neutrophil/lymphocyte
      ratio and coronary intervention. The preoperative use of aspirin was associated
      with a lower pMPO level and neutrophil/lymphocyte ratio. In conclusion, pMPO is
      positively associated with MI, the neutrophil/lymphocyte ratio and coronary
      intervention. The preoperative use of aspirin is associated with a lower pMPO
      level and neutrophil/lymphocyte ratio. pMPO may serve as a predictor of coronary
      intervention and as a potential therapeutic target for the reduction of
      inflammation in patients with CAD.

PMID- 25371763
TI  - De novo Assembly and Analysis of the Northern Leopard Frog Rana pipiens
      Transcriptome.
AB  - The northern leopard frog Rana (Lithobates) pipiens is an important animal model,
      being used extensively in cancer, neurology, physiology, and biomechanical
      studies. R. pipiens is a native North American frog whose range extends from
      northern Canada to southwest United States, but over the past few decades its
      populations have declined significantly and is now considered uncommon in large
      portions of the United States and Canada. To aid in the study and conservation of
      R. pipiens, this paper describes the first R. pipiens transcriptome. The R.
      pipiens transcriptome was annotated using Gene Ontology (GO), Kyoto Encyclopedia
      of Genes and Genomes (KEGG), and Eukaryotic Orthologous Groups (KOG).
      Differential expression analysis revealed universal and tissue specific genes,
      and endocrine-related genes were identified. Transcriptome assemblies and other
      sequence data are available for download. 

PMID- 25371764
TI  - Vaccination of children with a live-attenuated, intranasal influenza vaccine -
      analysis and evaluation through a Health Technology Assessment.
AB  - BACKGROUND: Influenza is a worldwide prevalent infectious disease of the
      respiratory tract annually causing high morbidity and mortality in Germany.
      Influenza is preventable by vaccination and this vaccination is so far
      recommended by the The German Standing Committee on Vaccination (STIKO) as a
      standard vaccination for people from the age of 60 onwards. Up to date a
      parenterally administered trivalent inactivated vaccine (TIV) has been in use
      almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV) has been
      approved additionally. Consecutively, since 2013 the STIKO recommends LAIV
      (besides TIV) for children from 2 to 17 years of age, within the scope of
      vaccination by specified indications. LAIV should be preferred administered in
      children from 2 to 6 of age. The objective of this Health Technology Assessment
      (HTA) is to address various research issues regarding the vaccination of children
      with LAIV. The analysis was performed from a medical, epidemiological and health
      economic perspective, as well as from an ethical, social and legal point of view.
      METHOD: An extensive systematic database research was performed to obtain
      relevant information. In addition a supplementary research by hand was done.
      Identified literature was screened in two passes by two independent reviewers
      using predefined inclusion and exclusion criteria. Included literature was
      evaluated in full-text using acknowledged standards. Studies were graded with the
      highest level of evidence (1++), if they met the criteria of European Medicines
      Agency (EMA)-Guidance: Points to consider on applications with 1. meta-analyses;
      2. one pivotal study. RESULTS: For the medical section, the age of the study
      participants ranges from 6 months to 17 years. Regarding study efficacy, in
      children aged 6 months to <=7 years, LAIV is superior to placebo as well as to a
      vac-cination with TIV (Relative Risk Reduction - RRR - of laboratory confirmed
      influenza infection approx. 80% and 50%, respectively). In children aged >7 to 17
      years (= 18th year of their lives), LAIV is superior to a vaccination with TIV
      (RRR 32%). For this age group, no studies that compared LAIV with placebo were
      identified. It can be concluded that there is high evidence for superior efficacy
      of LAIV (compared to placebo or TIV) among children aged 6 months to <=7 years.
      For children from >7 to 17 years, there is moderate evidence for superiority of
      LAIV for children with asthma, while direct evidence for children from the
      general population is lacking for this age group. Due to the efficacy of LAIV in
      children aged 6 months to <=7 years (high evidence) and the efficacy of LAIV in
      children with asthma aged >7 to 17 years (moderate evidence), LAIV is also very
      likely to be efficacious among children in the general population aged >7 to 17
      years (indirect evidence). In the included studies with children aged 2 to 17
      years, LAIV was safe and well-tolerated; while in younger children LAIV may
      increase the risk of obstruction of the airways (e.g. wheezing). In the majority
      of the evaluated epidemiological studies, LAIV proved to be effective in the
      prevention of influenza among children aged 2-17 years under everyday conditions
      (effectiveness). The trend appears to indicate that LAIV is more effective than
      TIV, although this can only be based on limited evidence for methodological
      reasons (observational studies). In addition to a direct protective effect for
      vaccinated children themselves, indirect protective ("herd protection") effects
      were reported among non-vaccinated elderly population groups, even at relatively
      low vaccination coverage of children. With regard to safety, LAIV generally can
      be considered equivalent to TIV. This also applies to the use among children with
      mild chronically obstructive conditions, from whom LAIV therefore does not have
      to be withheld. In all included epidemiological studies, there was some risk of
      bias identified, e.g. due to residual confounding or other methodology-related
      sources of error. In the evaluated studies, both the vaccination of children with
      previous illnesses and the routine vaccination of (healthy) children frequently
      involve cost savings. This is especially the case if one includes indirect costs
      from a societal perspective. From a payer perspective, a routine vaccination of
      children is often regarded as a highly cost-effective intervention. However, not
      all of the studies arrive at consistent results. In isolated cases, relatively
      high levels of cost-effectiveness are reported that make it difficult to perform
      a conclusive assessment from an economic perspective. Based on the included
      studies, it is not possible to make a clear statement about the budget impact of
      using LAIV. None of the evaluated studies provides results for the context of the
      German healthcare setting. The efficacy of the vaccine, physicians'
      recommendations, and a potential reduction in influenza symptoms appear to play a
      role in the vaccination decision taken by parents/custodians on behalf of their
      children. Major barriers to the utilization of influenza vaccination services are
      a low level of perception and an underestimation of the disease risk,
      reservations concerning the safety and efficacy of the vaccine, and potential
      side effects of the vaccine. For some of the parents surveyed, the question as to
      whether the vaccine is administered as an injection or nasal spray might also be
      important. CONCLUSION: In children aged 2 to 17 years, the use of LAIV can lead
      to a reduction of the number of influenza cases and the associated burden of
      disease. In addition, indirect preventive effects may be expected, especially
      among elderly age groups. Currently there are no data available for the German
      healthcare setting. Long-term direct and indirect effectiveness and safety should
      be supported by surveillance programs with a broader use of LAIV. Since there is
      no general model available for the German healthcare setting, statements
      concerning the cost-effectiveness can be made only with precaution. Beside this
      there is a need to conduct health eco-nomic studies to show the impact of
      influenza vaccination for children in Germany. Such studies should be based on a
      dynamic transmission model. Only these models are able to include the indirect
      protective effects of vaccination correctly. With regard to ethical, social and
      legal aspects, physicians should discuss with parents the motivations for
      vaccinating their children and upcoming barriers in order to achieve broader
      vaccination coverage. The present HTA provides an extensive basis for further
      scientific approaches and pending decisions relating to health policy.

PMID- 25371766
TI  - The 100 most cited psoriasis articles in clinical dermatologic journals, 1970 to
      2012.
AB  - BACKGROUND: Citation analysis is an effective way to gauge the impact of an
      article on the scientific community. OBJECTIVE: The purpose of this study was to
      perform a citation analysis of 24 clinical dermatologic journals from 1970 to
      2012, limited to the topic of psoriasis. METHODS: The authors conducted a search
      of "psoriasis" in the Science Citation Index from 1970 to 2012, including
      articles that have received 100 or more citations. The top 100 most cited
      articles were further analyzed for country, institution, and study type. RESULTS:
      Fifty of the top 100 most cited articles were from the United States and 81 of
      them were original articles. The majority of the top 100 classics were from
      dermatology programs in the United States, but institutions in the United Kingdom
      and Germany also made notable contributions. Citation classics in psoriasis were
      highly published from 1985 to 1989 and 2000 to 2004. LIMITATIONS: LIMITATIONS
      included potential neglect of a clinical dermatologic journal and the limited
      search term of "psoriasis." CONCLUSION: The great majority of citation classics
      were published in the premier dermatologic journals. The top-ranking dermatology
      programs in the United States produced the majority of the top 100 classics in
      psoriasis. The high number of citation classics from 1985 to 1989 correlates to
      the discovery of the immune-mediated pathogenesis of psoriasis at that time. The
      21st century brought forth the monumental development of biologic agents in
      psoriasis therapy, reflected by the high number of citation classics from 2000 to
      2004.

PMID- 25371765
TI  - High-Intensity Focused Ultrasound (HIFU) in Uterine Fibroid Treatment: Review
      Study.
AB  - BACKGROUND: High-intensity focused ultrasound (HIFU) is a highly precise medical
      procedure used locally to heat and destroy diseased tissue through ablation. This
      study intended to review HIFU in uterine fibroid therapy, to evaluate the role of
      HIFU in the therapy of leiomyomas as well as to review the actual clinical
      activities in this field including efficacy and safety measures beside the
      published clinical literature. MATERIAL/METHODS: An inclusive literature review
      was carried out in order to review the scientific foundation, and how it resulted
      in the development of extracorporeal distinct devices. Studies addressing HIFU in
      leiomyomas were identified from a search of the Internet scientific databases.
      The analysis of literature was limited to journal articles written in English and
      published between 2000 and 2013. RESULTS: In current gynecologic oncology, HIFU
      is used clinically in the treatment of leiomyomas. Clinical research on HIFU
      therapy for leiomyomas began in the 1990s, and the majority of patients with
      leiomyomas were treated predominantly with HIFUNIT 9000 and prototype single
      focus ultrasound devices. HIFU is a non-invasive and highly effective standard
      treatment with a large indication range for all sizes of leiomyomas, associated
      with high efficacy, low operative morbidity and no systemic side effects.
      CONCLUSIONS: Uterine fibroid treatment using HIFU was effective and safe in
      treating symptomatic uterine fibroids. Few studies are available in the
      literature regarding uterine artery embolization (UAE). HIFU provides an
      excellent option to treat uterine fibroids.

PMID- 25371767
TI  - A Randomized, Double-blind, Vehicle-controlled Trial of Luliconazole Cream 1% in
      the Treatment of Interdigital Tinea Pedis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of luliconazole cream 1% applied
      once daily for 14 days in patients with interdigital tinea pedis. DESIGN:
      Multicenter, randomized, double-blind, parallel-group, vehicle-controlled study.
      SETTING: Private dermatology clinics and clinical research centers in the United
      States and Central America. PARTICIPANTS: Three hundred twenty-two male and
      female patients >=12 years of age diagnosed with interdigital tinea pedis.
      MEASUREMENTS: Complete clearance (i.e., clinical and mycological cure), effective
      treatment, and fungal culture and susceptibility. RESULTS: At study Day 42,
      complete clearance was obtained by a larger percentage (14.0% [15/107] vs. 2.8%
      [3/107]; p<0.001) of patients treated with luliconazole cream 1% compared with
      vehicle. Also at Day 42, more luliconazole-treated patients compared with vehicle
      treated patients obtained effective treatment (32.7% vs. 15.0%), clinical cure
      (15.0% vs. 3.7%), and mycologic cure (56.1% vs. 27.1%). Erythema, scaling, and
      pruritus scores were lower for the luliconazole cream 1% group compared with
      vehicle on Day 14, Day 28, and Day 42. For all species and the same isolates, the
      MIC50/90 for luliconazole cream 1% was 6- to 12-fold lower than for other agents
      tested. No patients discontinued treatment because of a treatment-emergent
      adverse event. CONCLUSION: Luliconazole cream 1% was safe and well-tolerated and
      demonstrated significantly greater efficacy than vehicle cream in patients with
      interdigital tinea pedis.

PMID- 25371768
TI  - Actinic keratosis: update on field therapy.
AB  - Actinic keratosis is widely considered a field disease that is rarely limited to
      a single clinically apparent lesion. Field-directed therapies, such as ingenol
      mebutate, imiquimod, and photodynamic therapy, aim to treat not only clinically
      visible lesions, but also subclinical disease that is thought to exist along the
      same continuum as actinic keratosis and squamous cell carcinoma. These field
      treatments have shown efficacy compared to placebo as well as in long-term follow
      up studies when compared to lesion-directed cryotherapy alone. Field therapy in
      combination with lesion-directed treatment will allow the practitioner to further
      optimize efficacy as well as patient preference and convenience. As the incidence
      of nonmelanoma skin cancer continues to rise, these treatment modalities provide
      new options to halt the progression of actinic keratosis, and thereby reduce the
      incidence of nonmelanoma skin cancer and its burden on our healthcare system. 

PMID- 25371769
TI  - Evaluation of the efficacy and safety of a lidocaine and tetracaine (7%/7%) cream
      for induction of local dermal anesthesia for facial soft tissue augmentation with
      hyaluronic Acid.
AB  - Injection of dermal fillers for soft tissue augmentation is a minimally invasive
      cosmetic procedure with growing popularity. However, patients often express
      concern about pain with such procedures. A topical anesthetic cream formulated
      with lidocaine/tetracaine 7%7% was approved by the United States Food and Drug
      Administration in 2006 and recently reintroduced to the market for use during
      superficial dermatological procedures. A Phase 3 study was conducted to assess
      the efficacy and safety of lidocaine/tetracaine 7%7% cream versus placebo cream
      when used to induce local dermal anesthesia during injections with hyaluronic
      acid. Mean visual analog scale scores significantly favored lidocaine/tetracaine
      7%7% cream. A significant percent of subjects also indicated that
      lidocaine/tetracaine 7%7% cream provided adequate pain relief and that they would
      use lidocaine/tetracaine 7%7% cream again. Investigators also rated
      lidocaine/tetracaine 7%7% cream significantly better than placebo cream for
      providing adequate pain relief and on the assessment of pain scale.
      Lidocaine/tetracaine 7%7% cream was safe and well tolerated with most subjects
      reporting no erythema, edema, or blanching. No related adverse events were
      reported with lidocaine/tetracaine 7%7% cream; one related adverse event of
      erythema was reported with placebo cream. The results of this study indicate that
      lidocaine/tetracaine 7%7% cream is efficacious and safe at providing pain relief
      for soft tissue augmentation with hyaluronic acid. 

PMID- 25371770
TI  - Improvement of tear trough by monophasic hyaluronic Acid and calcium
      hydroxylapatite.
AB  - Tear trough deformities are a sign of facial aging. The anatomical base is well
      understood. In many patients, minimal invasive surgical procedures are useful to
      improve appearance. Here, the authors describe the use of monophasic hyaluronic
      acid dermal filler and calcium hydroxylapatite injection for correction. Forty
      female patients with a mean age of 50 years have been treated. On average, an
      improvement of one class of Hidman's severity score could be achieved by single
      treatment. Mean duration of the effect was 10.1 months for hyaluronic acid and
      12.8 months for calcium hydroxylapatite. Adverse effects were mild and temporary.
      Patients satisfaction was high (95%). 

PMID- 25371771
TI  - Skin substitutes: an overview of the key players in wound management.
AB  - In a relatively short timespan, a wealth of new skin substitutes made of
      synthetic and biologically derived materials have arisen for the purpose of wound
      healing of various etiologies. This review article focuses on providing an
      overview of skin substitutes including their indications, contraindications,
      benefits, and limitations. The result of this overview was an appreciation of the
      vast array of options available for clinicians, many of which did not exist a
      short time ago. Yet, despite the rapid expansion this field has undergone, no
      ideal skin substitute is currently available. More research in the field of skin
      substitutes and wound healing is required not only for the development of new
      products made of increasingly complex biomolecular material, but also to compare
      the existing skin substitutes. 

PMID- 25371772
TI  - On the computational ability of the RNA polymerase II carboxy terminal domain.
AB  - The RNA polymerase II carboxy terminal domain has long been known to play an
      important role in the control of eukaryotic transcription. This role is mediated,
      at least in part, through complex post-translational modifications that take
      place on specific residues within the heptad repeats of the domain. In this
      addendum, a speculative, but formal mathematical conceptualization of this
      biological phenomenon (in the form of a semi-Thue string rewriting system) is
      presented. Since the semi-Thue formalism is known to be Turing complete, this
      raises the possibility that the CTD - in association with the regulatory pathways
      controlling its post-translational modification - functions as a biological
      incarnation of a universal computing machine. 

PMID- 25371773
TI  - Flutamide-induced cytotoxicity and oxidative stress in an in vitro rat hepatocyte
      system.
AB  - Flutamide (FLU) is a competitive antagonist of the androgen receptor which has
      been reported to induce severe liver injury in some patients. Several
      experimental models suggested that an episode of inflammation during drug
      treatment predisposes animals to tissue injury. The molecular cytotoxic
      mechanisms of FLU in isolated rat hepatocytes using an in vitro oxidative stress
      inflammation system were investigated in this study. When a nontoxic hydrogen
      peroxide (H2O2) generating system (glucose/glucose oxidase) with peroxidase or
      iron(II) [Fe(II)] (to partly simulate in vivo inflammation) was added to the
      hepatocytes prior to the addition of FLU, increases in FLU-induced cytotoxicity
      and lipid peroxidation (LPO) were observed that were decreased by 6-N-propyl-2
      thiouracil or deferoxamine, respectively. N-Acetylcysteine decreased FLU-induced
      cytotoxicity in this system. Potent antioxidants, for example, Trolox ((+/-)-6
      hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), resveratrol (3,5,4'
      trihydroxy-trans-stilbene), and DPPD (N,N'-diphenyl-1,4-phenylenediamine) also
      significantly decreased FLU-induced cytotoxicity and LPO and increased
      mitochondrial membrane potential (MMP) and glutathione (GSH) levels in the H2O2
      generating system with peroxidase. TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin
      1-oxyl), a known reactive oxygen species (ROS) scavenger and superoxide dismutase
      mimetic, also significantly decreased toxicity caused by FLU in this system.
      These results raise the possibility that the presence or absence of inflammation
      may be another susceptibility factor for drug-induced hepatotoxicity.

PMID- 25371774
TI  - Protective effect of Momordica charantia fruit extract on hyperglycaemia-induced
      cardiac fibrosis.
AB  - In diabetes mellitus, cardiac fibrosis is characterized by increase in the
      deposition of collagen fibers. The present study aimed to observe the effect of
      Momordica charantia (MC) fruit extract on hyperglycaemia-induced cardiac
      fibrosis. Diabetes was induced in the male Sprague-Dawley rats with a single
      intravenous injection of streptozotocin (STZ). Following 4 weeks of STZ
      induction, the rats were subdivided (n = 6) into control group (Ctrl), control
      group treated with MC (Ctrl-MC), diabetic untreated group (DM-Ctrl), diabetic
      group treated with MC (DM-MC), and diabetic group treated with 150 mg/kg of
      metformin (DM-Met). Administration of MC fruit extract (1.5 g/kg body weight) in
      diabetic rats for 28 days showed significant increase in the body weight and
      decrease in the fasting blood glucose level. Significant increase in cardiac
      tissues superoxide dismutase (SOD), glutathione contents (GSH), and catalase
      (CAT) was observed following MC treatment. Hydroxyproline content was
      significantly reduced and associated morphological damages reverted to normal.
      The decreased expression of type III and type IV collagens was observed under
      immunohistochemical staining. It is concluded that MC fruit extract possesses
      antihyperglycemic, antioxidative, and cardioprotective properties which may be
      beneficial in the treatment of diabetic cardiac fibrosis.

PMID- 25371777
TI  - Clinical characteristics of cerebral venous thrombosis in a single center in
      Korea.
AB  - OBJECTIVE: The purpose of this study is to investigate the clinical
      characteristics of cerebral venous thrombosis (CVT) in a single center in Korea.
      METHODS: A total of 36 patients were diagnosed with CVT from August 2005 to May
      2013. The patient data regarding age, sex, disease stage, pathogenesis, location,
      laboratory findings, radiological findings, and treatment modalities were
      retrospectively collected. The results were compared with those of previous
      studies in other countries. RESULTS: The patient group comprised 21 men and 15
      women with a mean age of 46.9 years (ranging from three months to 77 years). The
      most common cause was a prothrombotic condition (8 patients, 22.2%). Within the
      patient group, 13 patients (36.1%) had a hemorrhagic infarction, whereas 23
      (63.9%) had a venous infarction without hemorrhage. By location, the incidence of
      hemorrhagic infarction was the highest in the group with a transverse and/or
      sigmoid sinus thrombosis (n=9); however, the proportion of hemorrhagic infarction
      was higher in the cortical venous thrombosis group (75%) and the deep venous
      thrombosis group (100%). By pathogenesis, the incidence of hemorrhagic infarction
      was the highest in the prothrombotic group (n=6), which was statistically
      significant (p=0.016). CONCLUSION: According to this study, CVT was more
      prevalent in men, and the peak age group comprised patients in the sixth decade.
      The most common cause was a prothrombotic condition. This finding was comparable
      with reports from Europe or America, in which CVT was more common in younger
      women. Hemorrhagic infarction was more common in the prothrombotic group
      (p=0.016) than in the non-prothrombotic group in this study.

PMID- 25371776
TI  - PKCdelta promotes high glucose induced renal tubular oxidative damage via
      regulating activation and translocation of p66Shc.
AB  - Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease
      (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a
      critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was
      involved in renal tubular injury via mitochondrial-dependent ROS production
      pathway, but little is known about the upstream signaling of p66Shc that leads to
      tubular oxidative damage under high glucose conditions. In this study, an
      increased PKCdelta and p66Shc activation and ROS production in renal tissues of
      patients with diabetic nephropathy were seen and further analysis revealed a
      positive correlation between the tubulointerstitial damage and p-PKCdelta, p
      p66Shc, and ROS production. In vitro, we investigated the phosphorylation and
      activation of p66Shc and PKCdelta during treatment of HK-2 cells with high
      glucose (HG). Results showed that the activation of p66Shc and PKCdelta was
      increased in a dose- and time-dependent manner, and this effect was suppressed by
      Rottlerin, a pharmacologic inhibitor of PKCdelta. Moreover, PKCdelta siRNA
      partially blocked HG-induced p66Shc phosphorylation, translocation, and ROS
      production in HK-2 cells. Taken together, these data suggest that activation of
      PKCdelta promotes tubular cell injury through regulating p66Shc phosphorylation
      and mitochondrial translocation in HG ambient.

PMID- 25371779
TI  - The spot sign predicts hematoma expansion, outcome, and mortality in patients
      with primary intracerebral hemorrhage.
AB  - OBJECTIVE: The purpose of this study was to retrospectively review cases of
      intracerebral hemorrhage (ICH) medically treated at our institution to determine
      if the CT angiography (CTA) 'spot sign' predicts in-hospital mortality and
      clinical outcome at 3 months in patients with spontaneous ICH. METHODS: We
      conducted a retrospective review of all consecutive patients who were admitted to
      the department of neurosurgery. Clinical data of patients with ICH were collected
      by 2 neurosurgeons blinded to the radiological data and at the 90-day follow-up.
      RESULTS: Multivariate logistic regression analysis identified predictors of poor
      outcome; we found that hematoma location, spot sign, and intraventricular
      hemorrhage were independent predictors of poor outcome. In-hospital mortality was
      57.4% (35 of 61) in the CTA spot-sign positive group versus 7.9% (10 of 126) in
      the CTA spot-sign negative group. In multivariate logistic analysis, we found
      that presence of spot sign and presence of volume expansion were independent
      predictors for the in-hospital mortality of ICH. CONCLUSION: The spot sign is a
      strong independent predictor of hematoma expansion, mortality, and poor clinical
      outcome in primary ICH. In this study, we emphasized the importance of hematoma
      expansion as a therapeutic target in both clinical practice and research.

PMID- 25371778
TI  - Association Factors for CT Angiography Spot Sign and Hematoma Growth in Korean
      Patients with Acute Spontaneous Intracerebral Hemorrhage : A Single-Center Cohort
      Study.
AB  - OBJECTIVE: This study was conducted to clarify the association factors and
      clinical significance of the CT angiography (CTA) spot sign and hematoma growth
      in Korean patients with acute intracerebral hemorrhage (ICH). METHODS: We
      retrospectively collected the data of 287 consecutive patients presenting with
      acute ICH who arrived within 12 hours of ictus. Baseline clinical and
      radiological characteristics as well as the mortality rate within one month were
      assessed. A binary logistic regression was conducted to obtain association
      factors for the CTA spot sign and hematoma growth. RESULTS: We identified a CTA
      spot sign in 40 patients (13.9%) and hematoma growth in 78 patients (27.2%). An
      elapsed time to CT scan of less than 3 hours (OR, 5.14; 95% CI, 1.76-15.02;
      p=0.003) was associated with the spot sign. A CTA spot sign (OR, 5.70; 95% CI,
      2.70-12.01; p<0.001), elevated alanine transaminase (GPT) level >40 IU (OR, 2.01;
      95% CI, 1.01-4.01; p=0.047), and an international normalized ratio >=1.8 or
      warfarin medication (OR, 5.64; 95% CI, 1.29-24.57; p=0.021) were independent
      predictors for hematoma growth. Antiplatelet agent medication (OR, 4.92; 95% CI,
      1.31-18.50; p=0.019) was significantly associated with hematoma growth within 6
      hours of ictus. CONCLUSION: As previous other populations, CTA spot sign was a
      strong predictor for hematoma growth especially in hyper-acute stage of ICH in
      Korea. Antithrombotics medication might also be associated with hyper-acute
      hematoma growth. In our population, elevated GPT was newly identified as a
      predictor for hematoma growth and its effect for hematoma growth is necessary to
      be confirmed through a further research.

PMID- 25371775
TI  - Nonalcoholic Fatty liver disease: pathogenesis and therapeutics from a
      mitochondria-centric perspective.
AB  - Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of disorders
      characterized by the accumulation of triglycerides within the liver. The global
      prevalence of NAFLD has been increasing as the obesity epidemic shows no sign of
      relenting. Mitochondria play a central role in hepatic lipid metabolism and also
      are affected by upstream signaling pathways involved in hepatic metabolism. This
      review will focus on the role of mitochondria in the pathophysiology of NAFLD and
      touch on some of the therapeutic approaches targeting mitochondria as well as
      metabolically important signaling pathways. Mitochondria are able to adapt to
      lipid accumulation in hepatocytes by increasing rates of beta-oxidation; however
      increased substrate delivery to the mitochondrial electron transport chain (ETC)
      leads to increased reactive oxygen species (ROS) production and eventually ETC
      dysfunction. Decreased ETC function combined with increased rates of fatty acid
      beta-oxidation leads to the accumulation of incomplete products of beta
      oxidation, which combined with increased levels of ROS contribute to insulin
      resistance. Several related signaling pathways, nuclear receptors, and
      transcription factors also regulate hepatic lipid metabolism, many of which are
      redox sensitive and regulated by ROS. 

PMID- 25371780
TI  - Anterior lumbar interbody fusion for the treatment of postoperative
      spondylodiscitis.
AB  - OBJECTIVE: To analyze the clinical courses and outcomes after anterior lumbar
      interbody fusion (ALIF) for the treatment of postoperative spondylodiscitis.
      METHODS: A total of 13 consecutive patients with postoperative spondylodiscitis
      treated with ALIF at our institute from January, 1994 to August, 2013 were
      included (92.3% male, mean age 54.5 years old). The outcome data including
      inflammatory markers (leukocyte count, C-reactive protein, erythrocyte
      sedimentation rate), the Oswestry Disability Index (ODI), the modified Visual
      Analogue Scale (VAS), and bony fusion rate using spine X-ray were obtained before
      and 6 months after ALIF. RESULTS: All of the cases were effectively treated with
      combination of systemic antibiotics and ALIF with normalization of the
      inflammatory markers. The mean VAS for back and leg pain before ALIF was 6.8+/
      1.1, which improved to 3.2+/-2.2 at 6 months after ALIF. The mean ODI score
      before ALIF was 70.0+/-14.8, which improved to 34.2+/-27.0 at 6 months after
      ALIF. Successful bony fusion rate was 84.6% (11/13) and the remaining two
      patients were also asymptomatic. CONCLUSION: Our results suggest that ALIF is an
      effective treatment option for postoperative spondylodiscitis.

PMID- 25371781
TI  - Postoperative flat back: contribution of posterior accessed lumbar interbody
      fusion and spinopelvic parameters.
AB  - OBJECTIVE: Posterior accessed lumbar interbody fusion (PALIF) has a clear
      objective to restore disc height and spinal alignment but surgeons may
      occasionally face the converse situation and lose lumbar lordosis. We analyzed
      retrospective data for factors contributing to a postoperative flat back.
      METHODS: A total of 105 patients who underwent PALIF for spondylolisthesis and
      stenosis were enrolled. The patients were divided according to surgical type
      [posterior lumbar inter body fusion (PLIF) vs. unilateral transforaminal lumbar
      interbody fusion (TLIF)], number of levels (single vs. multiple), and diagnosis
      (spondylolisthesis vs. stenosis). We measured perioperative index level lordosis,
      lumbar lordosis, pelvic tilt, sacral slope, pelvic incidence, and disc height in
      standing lateral radiographs. The change and variance in each parameter and
      comparative group were analyzed with the paired and Student t-test (p<0.05),
      correlation coefficient, and regression analysis. RESULTS: A significant
      perioperative reduction was observed in index-level lordosis following TLIF at
      the single level and in patients with spondylolisthesis (p=0.002, p=0.005).
      Pelvic tilt and sacral slope were significantly restored following PLIF
      multilevel surgery (p=0.009, p=0.003). Sacral slope variance was highly sensitive
      to perioperative variance of index level lordosis in high sacral sloped pelvis.
      Perioperative variance of index level lordosis was positively correlated with
      disc height variance (R(2)=0.286, p=0.0005). CONCLUSION: Unilateral TLIF has the
      potential to cause postoperative flat back. PLIF is more reliable than unilateral
      TLIF to restore spinopelvic parameters following multilevel surgery and
      spondylolisthesis. A high sacral sloped pelvis is more vulnerable to PALIF in
      terms of a postoperative flat back.

PMID- 25371782
TI  - Clinical significance of radiological stability in reconstructed thoracic and
      lumbar spine following vertebral body resection.
AB  - OBJECTIVE: Vertebral body replacement following corpectomy in thoracic or lumbar
      spine is performed with titanium mesh cage (TMC) containing any grafts.
      Radiological changes often occur on follow-up. This study investigated the
      relationship between the radiological stability and clinical symptoms. METHODS:
      The subjects of this study were 28 patients who underwent corpectomy on the
      thoracic or lumbar spine. Their medical records and radiological data were
      retrospectively analyzed. There were 23 cases of tumor, 2 cases of trauma, and 3
      cases of infection. During operation, spinal reconstruction was done with TMC and
      additional screw fixation. We measured TMC settlement in sagittal plane and
      spinal angular change in coronal and sagittal plane at postoperative one month
      and last follow-up. Pain score was also checked. We investigated the correlation
      between radiologic change and pain status. Whether factors, such as the kind of
      graft material, surgical approach, and fusion can affect the radiological
      stability or not was analyzed as well. RESULTS: Mean follow-up was 23.6 months.
      During follow-up, 2.08+/-1.65 degrees  and 6.96+/-2.08 degrees  of angular change
      was observed in coronal and sagittal plane, respectively. A mean of cage
      settlement was 4.02+/-2.83 mm. Pain aggravation was observed in 4 cases. However,
      no significant relationship was found between spinal angular change and pain
      status (p=0.518, 0.458). Cage settlement was seen not to be related with pain
      status, either (p=0.644). No factors were found to affect the radiological
      stability. CONCLUSION: TMC settlement and spinal angular change were often
      observed in reconstructed spine. However, these changes did not always cause
      postoperative axial pain.

PMID- 25371783
TI  - The clinical experience of computed tomographic-guided navigation system in c1-2
      spine instrumentation surgery.
AB  - OBJECTIVE: To identify the accuracy and efficiency of the computed tomographic
      (CT)-based navigation system on upper cervical instrumentation, particularly C1
      lateral mass and C2 pedicle screw fixation compared to previous reports. METHODS:
      Between May 2005 and March 2014, 25 patients underwent upper cervical
      instrumentation via a CT-based navigation system. Seven patients were excluded,
      while 18 patients were involved. There were 13 males and five females; resulting
      in four degenerative cervical diseases and 14 trauma cases. A CT-based navigation
      system and lateral fluoroscopy were used during the screw instrumentation
      procedure. Among the 58 screws inserted as C1-2 screws fixation, their precise
      positions were evaluated by postoperative CT scans and classified into three
      categories : in-pedicle, non-critical breach, and critical breach. RESULTS:
      Postoperatively, the precise positions of the C1-2 screws fixation were 81.1%
      (47/58), and 8.6% (5/58) were of non-critical breach, while 10.3% (6/58) were of
      critical breach. Most (5/6, 83.3%) of the critical breaches and all of non
      critical breaches were observed in the C2 pedicle screws and there was only one
      case of a critical breach among the C1 lateral mass screws. There were three
      complications (two vertebral artery occlusions and a deep wound infection), but
      no postoperative instrument-related neurological deteriorations were seen, even
      in the critical breach cases. CONCLUSION: Although CT-based navigation systems
      can result in a more precise procedure, there are still some problems at the
      upper cervical spine levels, where the anatomy is highly variable. Even though
      there were no catastrophic complications, more experience are needed for safer
      procedure.

PMID- 25371784
TI  - Risk factors associated with germinal matrix-intraventricular hemorrhage in
      preterm neonates.
AB  - OBJECTIVE: The purpose of this study is to identify the risk factors associated
      with the development of germinal matrix-intraventricular hemorrhage (GM-IVH) and
      the relationship of the severity of disease and prematurity. METHODS: A total of
      168 premature neonates whose birth weight <=1500 g or gestational age <=34 weeks
      were examined by cranial ultrasound (CUS) for detection of GM-IVH among the
      babies admitted between January 2011 and December 2012 in our medical center
      neonatal intensive care unit. The babies were divided into two groups : GM-IVH
      and non-IVH. Clinical presentations, precipitating factors of the patients and
      maternal factors were analyzed. RESULTS: In univariate analysis, gestational age,
      birth weight, delivery method, presence of premature rupture of membrane (PROM)
      and level of sodium and glucose were statistically meaningful factors (p<0.05).
      But only two factors, gestational age and presence of patent ductus arteriosus
      (PDA) were statistically meaningful in multivariate logistic regression (p<0.05).
      Delivery method [normal vaginal delivery (NVD) to Caeserean section] was
      borderline significant (p<0.10). CONCLUSION: Presence of PDA and gestational age
      were the important risk factors associated with development of GM-IVH.

PMID- 25371785
TI  - The effectiveness of endoscopic radiofrequency denervation of medial branch for
      treatment of chronic low back pain.
AB  - OBJECTIVE: The aim of this study is to evaluate the clinical results of
      endoscopic radiofrequency ablation of medial branch in patients with chronic low
      back pain originating from facet joints. METHODS: Between October 2010 and
      December 2013, 52 consecutive patients had suffering from chronic low back pain
      had undergone endoscopic radiofrequency denervation of medial branch of dorsal
      ramus. The clinical outcomes of these 52 patients were reviewed retrospectively.
      Preoperative and postoperative Visual Analogue Scale (VAS) and Korean version of
      Oswestry Disability Index (K-ODI), and patients' satisfaction with the procedure
      were assessed. RESULTS: The pain scores on the VAS for back pain had improved
      significantly from a preoperative mean of 7.1 to a postoperative mean of 2 at the
      last follow-up (p<0.001). The clinical outcomes based on the K-ODI had also
      improved significantly from a preoperative mean of 26.5% to postoperative mean of
      7.7% at the last follow-up (p<0.001). 80% of patients were satisfied with the
      procedure. There were no complications associated with the procedure. CONCLUSION:
      Our preliminary results demonstrate that endoscopic radiofrequency denervation of
      medial branch could be an effective alternative treatment modality for chronic
      back pain originating from facet joints that provides long-term pain relief.

PMID- 25371786
TI  - Very late stent thrombosis after sole stent-assisted coiling at the paraclinoid
      giant aneurysm : could prophylactic antiplatelet therapy be ceased at the only 1
      year after procedure?
AB  - Stent thrombosis is a major limitation of stent-assisted coiling, which is an
      effective method for treating wide-necked aneurysms. Although early in-stent
      thrombosis has been reported, very late stent thrombosis (VLST) (>1 year) has not
      been reported following implantation of a single self-expandable stent designed
      for coiling. Herein, the authors present a case of VLST that occurred 14 months
      after single stent implantation in a large paraclinoid aneurysm with an ultra
      wide neck involving the parent artery circumferentially. This case indicates the
      need for establishing guidelines regarding the optimal duration of prophylactic
      antiplatelet therapy following stent-assisted coiling, which remains undefined in
      the neuroendovascular field. 

PMID- 25371787
TI  - Endovascular treatment of symptomatic high-flow vertebral arteriovenous fistula
      as a complication after c1 screw insertion.
AB  - High-flow vertebral arteriovenous fistulas (VAVF) are rare complications of
      cervical spine surgery and characterized by iatrogenic direct-communication of
      the extracranial vertebral artery (VA) to the surrounding venous plexuses. The
      authors describe two patients with VAVF presenting with ischemic presentation
      after C1 pedicle screw insertion for a treatment of C2 fracture and nontraumatic
      atlatoaxial subluxation. The first patient presented with drowsy consciousness
      with blurred vision. The diffusion MRI showed an acute infarction on bilateral
      cerebellum and occipital lobes. The second patient presented with pulsatile
      tinnitus, dysarthria and a subjective weakness and numbness of extremities. In
      both cases, digital subtraction angiography demonstrated high-flow direct VAVFs
      adjacent to C1 screws. The VAVF of the second case occurred near the left
      posterior inferior cerebellar artery originated from the persistent first
      intersegmental artery of the left VA. Both cases were successfully treated by
      complete occlusion of the fistulous portion and the involved segment of the left
      VA using endovascular coil embolization. The authors reviewed the VAVFs after the
      upper-cervical spine surgery including C1 screw insertion and the feasibility
      with the attention notes of its endovascular treatment. 

PMID- 25371788
TI  - Coil embolization in ruptured inferior thyroid artery aneurysm with active
      bleeding.
AB  - We present a unique experience of urgent parent arterial embolization for
      treatment of an aneurysm of the inferior thyroid artery (ITA) that bled during
      tracheostomy. The event happened to a 69-year-old female patient with
      subarachnoid hemorrhage and hospital-acquired pneumonia that required
      tracheostomy. Abrupt and massive bleeding developed during the procedure, and the
      source could not be identified. Under manual compression, angiography revealed an
      8-mm aneurysm that arose from the inferior thyroid artery. The superselected
      parent artery of the aneurysm was successfully occluded with a single pushable
      coil. The patient's postoperative course was uneventful. 

PMID- 25371789
TI  - Cerebral arteriovenous malformation associated with moyamoya disease.
AB  - The coexistence of moyamoya disease (MMD) with an arteriovenous malformation
      (AVM) is exceedingly rare. We report two cases of AVM associated with MMD. The
      first case was an incidental AVM diagnosed simultaneously with MMD. This AVM was
      managed expectantly after encephalo-duro-arterio-synangiosis (EDAS) as the main
      feeders stemmed from the internal carotid artery, which we believed would be
      obliterated with the progression of MMD. However, the AVM persisted with
      replacement of the internal carotid artery feeders by new external carotid artery
      feeders from the EDAS site. The AVM was eventually treated with gamma knife
      radiosurgery considering an increasing steal effect. The second case was a de
      novo AVM case. The patient was initially diagnosed with MMD, and acquired an AVM
      eight years later that was slowly fed by the reconstituted anterior cerebral
      artery. Because the patient remained asymptomatic, the AVM is currently being
      closely followed for more than 2 years without further surgical intervention.
      Possible differences in the pathogenesis and the radiologic presentation of these
      AVMs are discussed with a literature review. No solid consensus exists on the
      optimal treatment of MMD-associated AVMs. Gamma knife radiosurgery appears to be
      an effective treatment option for an incidental AVM. However, a de novo AVM may
      be managed expectantly considering the possible risks of damaging established
      collaterals, low flow characteristics, and probably low risks of rupture. 

PMID- 25371790
TI  - Acute Shunt Malfunction Caused by Percutaneous Endoscopic Gastrostomy without
      Shunt Infection.
AB  - Percutaneous endoscopic gastrostomy tube placement is often performed in patients
      with a ventriculoperitoneal shunt and it has been accepted as a safe procedure.
      The authors report a case of a 50-year-old male who developed acute exacerbation
      of the hydrocephalus immediately after the percutaneous endoscopic gastrostomy
      tube placement without any signs of shunt infection, which has not been reported
      until now. After revision of the intraperitoneal shunt catheter, the sizes of the
      intracranial ventricles were normalized. 

PMID- 25371791
TI  - Endovascular rescue method for undesirably stretched coil.
AB  - Undesirable detachment or stretching of coils within the parent artery during
      aneurysm embolization can be related with thrombus formation, which can be caused
      occlusion of parent artery or embolic event(s). To escape from this situation,
      several rescue methods have been reported. A case with undesirably stretched coil
      in which another rescue method was used, is presented. When the stretched coil is
      still located in the coil delivery microcatheter, the stretched coil can be
      removed safely using a snare and a handmade monorail microcatheter. After a snare
      is lodged in the handmade monorail microcatheter, the snare is introduced over
      the coil delivery micorcatheter and located in the distal part of the stretched
      coil. After then, the handmade monorail microcatheter captures the stretched coil
      and the snare as one unit. This technique using a handmade monorail microcatheter
      and a snare can be a good rescue modality for the undesirably stretched coil,
      still remained within the coil delivery microcatheter. 

PMID- 25371792
TI  - Infected hydatid cysts bacteria in slaughtered livestock and their effects on
      protoscoleces degeneration.
AB  - BACKGROUND: The protoscoleces of fertile hydatid cysts are considered as major
      risks in surgery and producing secondary cysts if rupture the cyst during
      operation and, cause infecting the dogs with adult worm if eaten by this animal.
      Bacterial infection of the hydatid fluid can lead to sterilization of the cyst.
      OBJECTIVES: The aim of this study was to determine the bacterial infection rate
      of livestock hydatid cysts in Hamedan, Iran, and test the isolated bacteria
      effects on viable protoscoleces, in vitro. MATERIALS AND METHODS: A total of 5709
      slaughtered livestock were inspected to detect the presence of hydatid cysts. The
      hydatid fluid of all cysts was cultured separately to isolate and identify the
      bacteria. The effect of isolated bacteria was tested on viable protoscoleces in
      culture tubes, in vitro. The culture tubes were observed and examined under a
      light microscope every two hours for 24 hours, and then, after 36 and 48 hours.
      RESULTS: Infected cysts were found in 74% of animals in Hamedan (46% were
      calcified and the bacteria was isolated from 52%) and 62% in Borujerd. The
      isolated bacteria in the infected cysts were as follows: Escherichia coli, E.
      blattae, Klebsiella pnoumoniae, Proteus mirabilis, Enterobacter aerogenes,
      coagulase-positive and coagulase-negative Staphylococci, Pseudomonas aeruginosa
      and Edwardsiella tarda. The protoscoleces incubated with the isolated bacteria
      totally degenerated, but 55% of the protoscoleces in the control groups were
      intact and viable even after one week. CONCLUSIONS: This study indicated a high
      percentage of cysts bacterial infections in two provinces of Iran. The common
      isolated bacteria were E. coli and Klebsiella. The isolated bacteria degenerated
      the protoscoleces during short-time incubation, in vitro.

PMID- 25371793
TI  - In Vitro Study of Potentially Probiotic lactic Acid Bacteria Strains Isolated
      From Traditional Dairy Products.
AB  - BACKGROUND: Probiotic microorganisms are selected based on their long history of
      use as well as their lack of side effects. Nowadays, the consumption of probiotic
      products is growing intensively in developing countries. Researchers who work in
      the food industry and research centers pay more attention to the identification
      of new probiotic bacteria with better performance characteristics as well as
      investigation of their performance because these findings can be very effective
      in promoting sale and consumption of these products. OBJECTIVES: HENCE, THIS
      STUDY WAS PERFORMED FOLLOWING THESE OBJECTIVES: isolating indigenous lactic acid
      bacteria from traditional dairy products in Markazi Province, screening strains
      with probiotic characteristics, identifying strains and performing microbial
      collection of probiotic strains with indigenous potential. MATERIALS AND METHODS:
      In this study, the samples were screened from traditional dairy products, such as
      fresh yogurt, curd, Tarhana and Ghareghoroot of Markazi Province villages.
      Samples were enriched in de Man, Rogosa and Sharpe (MRS) broth, and different
      strains were isolated and purified from this culture on MRS agar medium. Isolated
      strains were investigated by microscopic observations, considering the following
      factors: catalase capability, resistance to acid and bile, bile salt hydrolysis
      and antibiotic susceptibility pattern. RESULTS: Nineteen Gram-positive and
      catalase-negative strains belonging to the Lactobacillus genus were isolated from
      the above-mentioned diary samples. Seven strains were resistant to acid and bile
      in which acid resistance was between 21.08% and 122.33% and bile resistance was
      between 94.08% and 152.93%, respectively. All isolated strains were susceptible
      to different antibiotics and a small percentage had the ability to hydrolyze
      Sodium Taurocholate. CONCLUSIONS: There are many of different species of
      Lactobacillus probiotics in traditional dairy products of the Markazi province,
      based on the findings of this study. It is recommended for researchers to isolate
      these strains and investigate their probiotic characteristics in order to
      reproduce them for use in food production as well as for medical treatment.

PMID- 25371794
TI  - beta-D-Glucan Assay in Diagnosis and Monitoring the Systemic Candidiasis in a Rat
      Model.
AB  - BACKGROUND: Determination of beta-D-Glucan (BDG) in the serum aids to diagnose
      the invasive fungal infections. The current study evaluated the diagnostic
      potential value of BDG assay in monitoring the disease in experimental systemic
      candidiasis in a rat model. The results can provide a useful preliminary data to
      improve this approach in developing countries. OBJECTIVES: The present study
      aimed to evaluate beta-D-Glucan assay in diagnosis and monitoring the systemic
      candidiasis in a rat model. MATERIALS AND METHODS: Twenty one rats were infected
      with 10(6) Candida albicans blastospore per rat. Twelve rats were considered as
      the negative controls (six immunocompromised rats without infection and six
      intact rats). During a week, every 24 hours the BDG sera level was determined by
      both Fungitell and Wako kits. To confirm the systemic infection in each rat, the
      suspensions of their internal organs were cultivated on agar plates and the
      number of colony forming units (CFU) of C. albicans was counted. RESULTS: All the
      infected rats were positive with BDG tests. An increasing level of BDG was
      observed during early days after injection. The cutoff value for discrimination
      of BDG positive sera was obtained from the negative sera by the Fungitell kit.
      The sensitivity, specificity, positive and negative predictive values assessed
      for the Fungitell kit were 95%, 66.6%, 90.47% and 80%, respectively. These
      criteria for those of Wako were 90%, 83.3%, 94.7% and 71.4%, respectively.
      CONCLUSIONS: While BDG assay seems to be a sensitive and specific adjunctive tool
      to diagnose and monitor the experimental systemic candidiasis, it seems that
      measuring the positive cutoff value in different laboratory conditions is
      necessary for favorable establishment of these tests.

PMID- 25371795
TI  - Immunofluorescence assay and PCR analysis of cryptosporidium oocysts and species
      from human feacal specimens.
AB  - BACKGROUND: Cryptosporidium spp. is a widespread protozoan parasite involving
      humans and animals. OBJECTIVES: This study was carried out to evaluate the
      immunofluorescence assay (IFA) and PCR results for more accurate diagnosis of
      faecal specimens. PATIENTS AND METHODS: Forty six faecal human specimens of
      Cryptosporidium oocysts were examined by PCR and IFA in Calgary, Canada. In
      statistical analysis, sensitivity and positive predictive value were detected by
      IFA. RESULTS: Among 46 faecal samples, 9 (19.6%) were IFA-positive and 10 (21.7%)
      PCR-positive. Faecal smears of both PCR- and IFA-positive shown that the
      reproducibility was 90.9% for PCR-DNA and 81.8% for IFA. In Our findings, PCR 
      DNA showed that diagnosis cryptosporidiosis 2.1% was more sensitive than IFA. Two
      different oocysts sizes were visualized by IF microscopy which belonged to
      different species. Furthermore, PCR analysis with primers against the 18S rRNA
      gene indicated two genotypes of C. hominis and C. parvum, 500-650 base pairs
      (bp). In this study, the golden standard was the PCR. In statistical analyses,
      IFA had positive predictive value (PPV) of 81.8% with 81.8% sensitivity, whereas
      negative predictive value (NPV) was 1% with 0.97% specificity. CONCLUSIONS: PCR
      showed more sensitivity than IFA for tracking Cryptosporidium oocysts as well as
      detection of species in faecal human specimens.

PMID- 25371796
TI  - Intensity of HLA-A2 Expression Significantly Decreased in Occult Hepatitis B
      Infection.
AB  - BACKGROUND: Occult hepatitis B infected (OBI) patients cannot eradicate hepatitis
      B virus (HBV)-DNA from their liver and peripheral blood, completely. OBJECTIVES:
      The main aim of this study was to investigate the rate of HLA-A2 expression on
      peripheral blood mononuclear cells (PBMCs) of patients with OBI. MATERIALS AND
      METHODS: In this experimental study, intensity of HLA-A2 was measured on the
      PBMCs of 57 OBI patients and 100 HBsAg-/anti-HBc+/HBV-DNA samples were enrolled
      as controls; measurements were performed using the flow cytometry technique.
      RESULTS: Flow cytometric analysis indicated that 19 (33.3%) OBI patients and 28
      (28%) controls expressed HLA-A2 antigen on their PBMCs. There was no significant
      difference between the two groups regarding the rate of individuals expressing
      HLA-A2 antigen. Statistical analyses showed that the intensity of HLA-A2
      expression significantly decreased in OBI patients (3.58 +/- 0.1) in comparison
      to healthy controls (4.21 +/- 0.25; P < 0.001). CONCLUSIONS: According to these
      results it can be concluded that decreased intensity of HLA-A2 on the PBMCs of
      OBI patients may lead to resistance of HBV in the patients.

PMID- 25371797
TI  - Staphylococcus aureus Typing by Digestion of Protein A Coding Gene Using Bsp143I.
AB  - BACKGROUND: Protein A is the virulence factors of Staphylococcus aureus rolling
      in its pathogenesis, and its gene is used for typing. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) with different enzymes has
      been used for this action. OBJECTIVES: In this study, we used Bsp143I enzyme for
      digestion of the gene, coding protein A (spa gene) in S. aureus. The bacteria
      were isolated from patients and healthy carriers in Gorgan, north of Iran.
      PATIENTS AND METHODS: DNAs of 128 S. aureus subjects (53 from healthy carriers
      and 75 from patients) were extracted and amplified using specific primers of the
      spa gene. The product was digested by Bsp143I enzyme and its pattern was assessed
      by gel electrophoresis. RESULTS: There were seven spa types among the tested S.
      aureus samples, among which six types differed in the repeated X region of the
      spa gene, but the seventh type had a deletion on one of BSP143I restriction
      sites. The frequency of spa types among isolated S. aureus samples as well as
      healthy carriers was six and five, respectively. S. aureus isolated from wounds
      showed the most diverse spa types (five) among clinical samples. Types 1, 2 and 4
      were observed in all clinical samples, while only one case of type 3 was
      identified among patients, whereas this type constituted over 32% of the isolates
      among carriers. We found seven and four spa types among methicillin-resistant S.
      aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) isolates, respectively.
      CONCLUSIONS: Our results showed that typing the spa gene using PCR-RFLP using
      Bsp143I was an acceptable method for typing S. aureus. Furthermore, this survey
      showed that the types in healthy carriers and MSSA were more variable than
      patient and MRSA isolates, respectively. We used the Bsp143I enzyme, which was
      not used in any previous studies on the spa gene. The results of this study
      suggested that we can use PCR-RFLP of spa gene by Bsp143I for molecular typing
      and sequencing of S. aureus, instead of relatively expensive methods. This method
      is relatively rapid and inexpensive, and can be accomplished in centers with
      conventional molecular facilities.

PMID- 25371798
TI  - Isolation, Characterization and Selection of Avermectin-Producing Streptomyces
      avermitilis Strains From Soil Samples.
AB  - BACKGROUND: Streptomyces avermitilis, belonging to Actinomycetes, is specialized
      for production of avermectin, used as an anthelmintic and insecticidal agent. It
      is mostly found in soil and its isolation is very crucial for medically important
      avermectin production. OBJECTIVES: In the present study, 10 bacterial isolates
      lacking antimicrobial activities were isolated from the soil samples collected
      from different areas of Lahore, Pakistan. MATERIALS AND METHODS: Three
      distinctive localities of Lahore were opted for soil assortment to isolate S.
      avermitilis. About 50 isolates of Streptomyces species were attained through
      selective prescreening procedures. All of these isolates were studied for
      production of the secondary metabolite, avermectin. Different test like soluble
      pigment color and melanin formation were used for identification. Biochemical
      characterizations of those isolates closely resembling the control in
      morphological characteristics, soluble pigment color and melanin formation tests
      were performed. RESULTS: The 10 selected isolates were identified as the
      avermectin-producing strain by fermentation and characterized on ISP2 medium for
      aerial and reverse side mycelia color, soluble pigment color and melanin
      formation, in comparison with S. avermitilis DSM 41445. The best avermectin
      producing isolate S1-C (10.15 mg/L) showed similar result as S. avermitilis DSM
      41445, when subjected for culture characteristics analysis in different media
      along with biochemical characterization. CONCLUSIONS: From the results, it was
      concluded that agricultural lands around Pakistan Council of Scientific and
      Industrial Research (PCSIR) Campus Lahore were rich sources of industrially
      important Streptomyces, especially S. avermitilis.

PMID- 25371799
TI  - Characterization and Transferring of Human Rotavirus Double-Layered Particles in
      MA104 Cells.
AB  - BACKGROUND: Rotavirus (RV) is a major cause of gastroenteritis in infants and
      children and is one of the most severe public health problems. Rotaviruses outer
      layer contains two proteins including VP4 and VP7. These proteins are necessary
      for host-cell binding and penetration. TLP (triple layer virus particle) of RV is
      a complete infectious virion that binds to the target cells and internalized at
      the cytoplasm. The DLP (double layer virus particle) is a non-infectious particle
      that is formed through exclusion of the outer layer proteins including VP4 and
      VP7. These DLPs are the transcriptionally active forms of rotavirus. OBJECTIVES:
      The aim of this study was to transfer DLP of RV into cytoplasm of MA104 cells by
      Lipofectamine and to analyze their replication. MATERIALS AND METHODS: Initially,
      rotavirus was purified by CsCl discontinuous gradient and DLP was separated from
      TLP based on density differences. For confirmation, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) of the proteins were conducted Then
      the purified DLP of RV was transferred into MA104 cells using Lipofectamine.
      RESULTS: We attempt to avoid the attachment and entry of the rotavirus by using
      Lipofectamine to mediate the delivery of viral particles directly into the
      cytoplasm. DLP was endocytosed into the cytoplasm following treatment by
      Lipofectamine and then replicated in cytoplasm. CONCLUSIONS: Therefore the non
      infectious DLPs were became infectious if introduced into the cytoplasm of
      permissive and cancerous cells, without passing attachment and entry process.

PMID- 25371800
TI  - Survival rates of human immunodeficiency virus and tuberculosis co-infected
      patients.
AB  - BACKGROUND: At present, limited clinical data is available regarding survival
      rates of patients co-infected with human immunodeficiency virus
      (HIV)/tuberculosis (TB) in developing countries. OBJECTIVES: The present study
      aimed to evaluate the effect of HIV infection on the survival chances of active
      TB adults who disclosed their symptoms of TB in this part of Iran. PATIENTS AND
      METHODS: The records and data of 807 patients only infected with TB and 21 co
      infected patients with HIV/TB, who were admitted to primary health care units in
      Iran, were evaluated. Their survival time was analyzed using the Kaplan-Meier
      Estimator, Log-rank test and SPSS version 16. RESULTS: Cox regression analysis
      showed that co-infection with HIV significantly affects the survival rate of TB
      patients so that the rate of death was 20.7 (8.1-53) times more than TB infected
      patients alone. Also, married patients with tuberculosis were 2.7 times more at
      risk of death than single subjects. We also confirmed that in HIV/TB positive
      patients, married individuals were more prone to death than single subjects (P
      value < 0.001). CONCLUSIONS: Our results denote the need to progress diagnostic
      and preventive measures in this part of Iran.

PMID- 25371801
TI  - Optimization of L-Tryptophan Biosynthesis From L-Serine of Processed Iranian Beet
      and Cane Molasses and Indole by Induced Escherichia coli ATCC 11303 Cells.
AB  - BACKGROUND: L-tryptophan is an important ingredient in medicines, especially in
      neuromedicines such as antidepressants. Many commercial processes employ various
      microorganisms with high tryptophan synthase activity to produce L-tryptophan
      from indole and L-serine, but these processes are very costly due to the costs of
      precursors, especially L-serine. OBJECTIVES: For this reason, we studied the
      ability to use processed Iranian cane and beet molasses as L-serine sources for L
      tryptophan production, which enables us to reach a cost-effective process.
      MATERIALS AND METHODS: Whole cells of Escherichia coli ATCC 11303 were induced
      for L-tryptophan synthase by addition of indole to the growth medium and
      bacterial cells harvested from the growth medium were used as biocatalysts in the
      production medium. Conditions of the production medium were optimized and Iranian
      cane and beet molasses were processed by solvent extraction with ethanol and n
      butanol and used as L-serine sources of the production medium. Amount of L
      tryptophan and theoretical yield of L-tryptophan production were determined by
      High Performance Liquid Chromatography and by a colorimetrical method on the
      basis of the remaining indole assay, respectively. RESULTS: L-tryptophan
      production increased by 15 folds, when indole was used as an inducer. L
      tryptophan was produced from processed Iranian beet molasses in satisfactory
      amounts (0.53 mM) and no exogenous pyridoxal phosphate was required as a cofactor
      under our experimental conditions. CONCLUSIONS: The obtained results proved that
      Iranian beet molasses include significant amounts of L-serine that makes them a
      suitable substitution for L-serine. Findings of the present study give impetus to
      use of Iranian beet molasses for cost-effective L-Trp production in the amino
      acid industry.

PMID- 25371802
TI  - Isolation, Identification and Antimicrobial Susceptibility Pattern of Tatumella
      ptyseos Strains Isolated From Powdered Infant Formula Milk Consumed in Neonatal
      Intensive Care Unit: First Report From Iran.
AB  - BACKGROUND: Tatumella ptyseos is a rod-shaped, Gram-negative, facultative, and
      anaerobic bacteria categorized in the Enterobacteriaceae family. It is a rare
      food-borne opportunistic pathogen which causes neonatal sepsis, bacteremia, and
      urinary tract infections. T. ptyseos has been also cultured from various food
      sources around the world. OBJECTIVES: It is difficult to determine the source of
      the infection in the patients (especially newborns) due to low information about
      the epidemiology of T. ptyseos. The current study aimed to investigate the
      isolation, identification and antimicrobial susceptibility pattern of T. ptyseos
      strains from the consumed powdered infant formula milk (PIF) in hospital neonatal
      intensive care unit (NICU). MATERIALS AND METHODS: A total of 125 powdered infant
      formula milk (PIF) samples were purchased from drug stores from June 2011 to
      March 2012. T. ptyseos was isolated according to food and drug administration
      (FDA) method. For final confirmation, biochemical testes embedded in API-20E
      system were used. Drug susceptibility test was performed using the disc diffusion
      method, according to clinical and laboratory standard institute (CLSI)
      recommendations. RESULTS: Results of the study showed that, out of 125 samples,
      T. ptyseos was isolated from four (3/2%) PIF samples. All isolated strains (100%)
      were resistant to ampicillin, carbenicillin, cotrimoxazole and amoxicillin.
      CONCLUSIONS: The present study was the first report on the isolation and
      identification of T. ptyseos from PIF in Iran. T. ptyseos are frequently present
      in various kinds of foods; therefore, further investigation on these samples is
      required. It is necessary to track the T. ptyseos in a wide variety of foods and
      individuals especially in immunocompromised people such as human immunodeficiency
      virus (HIV)-positive patients to reveal the possible routes of transmission of
      this pathogen to humans. In addition, molecular studies are required to determine
      the genetic relationship between T. ptyseos strains isolated from different
      sources.

PMID- 25371803
TI  - Evaluation of an Iranian Home-made Helicobacter pylori Stool Antigen ELISA Kit.
AB  - BACKGROUND: Current diagnosis of Helicobacter pylori infection by biopsy-based
      tests requires invasive sampling. Non-invasive methods such as the H. pylori
      stool-antigen (HpSA) test may be the best alternative for diagnosis of active
      infection. However, due to the presence of antigenic-diversity among the strains,
      various commercial tests have shown some discrepancies in different geographical
      areas. OBJECTIVES: This study evaluates a homemade HpSA kit developed by using
      the H. pylori antigens from Iranian-isolates for detection of H. pylori in the
      stool of infected patients. PATIENTS AND METHODS: Based on the endoscopic
      features and/or a rapid-urease test (RUT), 30 child and 50 adult patients, were
      recruited. From these candidates, three biopsies for RUT, culture and histology,
      and a stool-sample, were obtained. Patients were considered as H. pylori-positive
      if culture alone or RUT plus histology were found to be positive. Presence of H.
      pylori antigens in their stools was detected by the homemade HpSA test and an
      imported HpSA kit (Immundiagnostik, Germany). RESULTS: Using the biopsy-based
      tests with RUT, histology and culture, 53% (16/30) of children were diagnosed as
      H. pylori-positive while using the imported kit 57% and the homemade kit 50% of
      the candidates showed positive results. Also by the biopsy-based tests, 54% of
      the adults were diagnosed as H. pylori-positive while by the homemade kit 56%
      showed positive results. Considering the biopsy-based tests as the gold standard,
      sensitivity and specificity for the imported kit was 94% and 86%, respectively,
      while the mean sensitivity and specificity for the homemade kit was 96% and 98%,
      respectively. CONCLUSIONS: The homemade kit, compared with the imported kit and
      biopsy-proven tests may be a valid and reliable method for determining the
      presence of H. pylori infection in Iran.

PMID- 25371804
TI  - Evaluation of Conidia-Dust Formulation of the Entomopathogenic Fungus,
      Metarhizium anisopliae to Biocontrol the Brown-Banded Cockroach, Supella
      longipalpa F.
AB  - BACKGROUND: The brown-banded cockroach Supella longipalpa (F.) as a mechanical
      vector of pathogens and source of allergens has recently become widespread in the
      city of Ahvaz, southwestern Iran. OBJECTIVES: This research was done to evaluate
      the efficacy of a dust-formulation of Metarhizium anisopliae isolate IRAN 437C,
      as a common entomopathogenous fungus, against S. longipalpa. MATERIALS AND
      METHODS: Conidia dust-formulations of M. anisopliae were prepared in proportions
      of 1%, 5%, 10%, 25%, 50% and 100% with bad wheat flour as the carrier.
      Cockroaches were exposed to surfaces treated with 1.5 mg/cm(2) of the
      formulations under laboratory and semi-field conditions. RESULTS: Cockroach
      mortality rates increased and survival times (ST50) decreased with an increased
      proportion of conidia from 1% to 100% but records taken for mortality and
      survival time from proportions of 25%, 50% and 100% were not significantly
      different. The mortality rates reached 100% and 90-100% in adults and nymphs,
      respectively on the seventh day. The lowest ST50 was related to the proportion of
      100% (3 days). Probit analysis indicated LD50 and LD90 values of 1.7 * 10(6) and
      1.7 * 10(7) conidia/cm(2) for adults and these values changed to 4.5 * 10(6) and
      2.9 * 10(7) for third and fourth instar nymphs at three days post exposure.
      Proportion of 25% caused mortality rates of 87%, 81% and 73% in adult, adult &
      nymph and nymph populations, respectively at four days after exposure under room
      conditions. CONCLUSIONS: Conidia dust-formulation of M. anospliae isolate IRAN
      437C could present a promising alternative to control the brown-banded cockroach.

PMID- 25371806
TI  - The First Macrolide-Resistant Bordetella pertussis Strains Isolated From Iranian
      Patients.
AB  - BACKGROUND: Whooping cough was considered as one of the major causes of childhood
      morbidity and mortality worldwide. Resistant isolates of Bordetella pertussis to
      macrolides in some countries have been recently reported. OBJECTIVES: Recent
      reports on macrolide-resistant B. pertussis isolates and lack of evidence for
      such resistance in clinical isolates of the Iranian patients led the authors of
      the current study to study antibiotic susceptibility of the collected isolates in
      the country. Susceptibility of the B. pertussis isolates to three antibiotics was
      studied. Relatedness of the strains recovered in this research was also examined.
      MATERIALS AND METHODS: The antibacterial activities of erythromycin,
      azithromycin, and clarithromycin antibiotics against the recovered isolates of
      779 nasopharyngeal swabs were examined using MIC (Minimum Inhibitory
      Concentration) method. Relationship of the strains was characterized by Pulsed
      field Gel Electrophoresis (PFGE). RESULTS: Among the specimens, 11 cases (1.4%)
      were culture-positive. Among these isolates, only two isolates had high MIC
      values for erythromycin and clarithromycin. Pulsed-field gel electrophoresis
      analysis of the isolates revealed 6 PFGE profiles (A-F) among which three and two
      isolates had the same patterns in profiles A and B, respectively. CONCLUSIONS:
      Azithromycin can be a good drug of choice to treat patients infected by B.
      pertussis in Iran. Clonal relationship of the isolates showed that the same B.
      pertussis strains were isolated from different patients in Iran.

PMID- 25371805
TI  - Analysis of Virulence Genes Among Methicillin Resistant Staphylococcus aureus
      (MRSA) Strains.
AB  - BACKGROUND: Staphylococcus aureus is amongst major human pathogens both in
      hospitals and the community. This bacterium is an opportunistic pathogen
      responsible for a large number of self-limiting and even life-threatening
      diseases in humans. Methicillin resistant S. aureus (MRSA) strains are common
      causes of emerging nosocomial infections and are considered as a major problem
      for public health. OBJECTIVES: WE AIMED TO STUDY THE PROFILE OF SOME VIRULENCE
      GENES INCLUDING: sea, seb, sed, tst, eta, etb, LuKS/F-PV, hla and hld in
      methicillin-resistant S. aureus by the PCR technique. MATERIALS AND METHODS: A
      total of 345 isolates of S. aureus were collected from clinical specimens of
      patients referred to teaching hospitals of Shiraz; identification was done by
      biochemical (catalase, coagulase and DNase) and molecular tests. One hundred and
      forty six isolates of methicillin-resistant S. aureus (MRSA) were obtained and
      the presence of some toxin genes in these isolates was investigated by the
      polymerase chain reaction (PCR) technique. RESULTS: The results showed that among
      the 345 isolates of S. aureus, 148 were confirmed as MRSA by screening with the
      cefoxitin disc diffusion (30 ug) method. Also among the 148 MRSA isolates, 146
      isolates were confirmed as methicillin-resistant by molecular methods. The
      results showed that the frequency of methicillin-resistant and methicillin
      sensitive S. aureus isolates during 2012 to 2013 in Namazi and Faghihi hospitals
      were 146 (42.3%) and 199 (57.7%), respectively. Besides, among the 146 confirmed
      MRSA isolates, 36.98% (54 isolates) and 63.02% (92 isolates) were related to
      female and male, respectively. The largest number of cases belonged to sputum
      samples (58 out of 146). The frequency of the eta, etb, sed, LuKS/F-PV, seb, tst,
      sea, hld and hla genes were 0.68%, 2.05%, 2.05%, 5.47%, 10.95%, 11.64%, 27.39%,
      84.24% and 93.15%, respectively. In addition, amongst all examined genes, hla
      (93.15%) and eta (0.68%) genes had the highest and lowest frequencies,
      respectively. The greatest coexistence of genes was observed for the hla + hld
      gene combination (48.83%). The results of our study indicate that 98.63% of the
      isolates were positive for at least one of the virulence genes. CONCLUSIONS: The
      relative higher frequency of some virulence genes in this study may reflect the
      emergence of isolates containing these genes in Shiraz medical centers.

PMID- 25371807
TI  - Prevalence of Quinolone Resistance Among Extended-Spectrum beta -Lactamase
      Producing Uropathogenic Klebsiella pneumoniae.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL) production is the major
      resistance mechanism to beta-lactam antibiotics in Enterobacteriaceae. In
      addition, emergence of plasmid-mediated quinolone resistance (PMQR) in ESBL
      producing isolates has become a global threat for treatment of these infections.
      OBJECTIVES: We investigated the association between ESBL production and quinolone
      resistance in urinary isolates of K. pneumoniae. PATIENTS AND METHODS: A total of
      196 urinary isolates of K. pneumoniae were collected from Imam Hussein Hospital
      in Tehran during a four year period (2008-2012). Antibiotic susceptibility was
      determined by disc diffusion and ESBL production was screened using the
      phenotypic confirmatory test (PCT). RESULTS: All isolates were susceptible to
      imipenem. Resistance to piperacillin and cefotaxime were 66.3% and 50.5%,
      respectively. Resistance to ceftazidime, amoxiclave, aztreonam, ceftriaxone,
      cefepime, nitrofurantoin, gentamicin, ciprofloxacin, nalidixic acid, ofloxacin,
      norfloxacin, levofloxacin, amikacin and pipracilin/tazobactam were less than 50%.
      ESBL production was detected in 92 isolates (46.9%) of which, 61.9% were
      resistant to nalidixic acid and 65.2% to ciprofloxacin. Multidrug-resistance was
      observed in 96.7% of ESBL producers. CONCLUSIONS: Our results showed coexistence
      of ESBL and quinolone resistance in the majority of the uropathogenic K.
      pneumoniae test isolates suggesting that care should be taken for the choice of
      antibiotic therapy.

PMID- 25371808
TI  - Interferon-gamma and interlukin-4 patterns in BALB/c mice suffering from
      cutaneous leishmaniasis treated with cantharidin.
AB  - BACKGROUND: Cutaneous leishmaniasis is a health problem in the world. Lesions
      should be treated on cosmetically or functionally important sites, such as the
      face and hands. Cantharidin is a terpenoid compound produced naturally by beetles
      of Meloidae and Oedemeridae families. OBJECTIVES: The current study aimed to
      investigate the effect of cantharidin on Cutaneous Leishmaniasis (CL) lesions and
      IFN-gamma and IL-4 patterns in infected BALB/c mice. MATERIALS AND METHODS:
      INFECTED BALB/C MICE WERE DIVIDED INTO FIVE GROUPS AS: untreated (control group),
      eucerin-treated and 0.05%, 0.1% and 0.5% cantharidin-treated. Lesions diameter
      was measured by Vernier caliper every three days for four weeks. Cytokines levels
      were measured by enzyme-linked immunosorbent assay (ELISA) using U-CyTech kit.
      RESULTS: The results indicated that treatment with cantharidin exacerbates
      lesions compared with the controls, except for 0.05% cantharidin dose that
      restrained lesion growth significantly. Interferon gamma level in cantharidin
      treated groups was significantly less than that of the control group. But
      interlukin-4 level was similar among the groups. CONCLUSIONS: The current study
      results indicated that high doses of cantharidin exacerbates leishmaniasis
      lesion, but low dose of cantharidin inhibits lesion growth.

PMID- 25371809
TI  - Toxoplasma gondii in Cattle, Camels and Sheep in Isfahan and Chaharmahal va
      Bakhtiary Provinces, Iran.
AB  - BACKGROUND: Toxoplasma gondii is a zoonotic parasite, which is assumed to have
      cosmopolitan distribution. OBJECTIVES: Adopting a cross-sectional study design
      the current research aimed to determine the occurrence of the parasite in cattle,
      camels and sheep in Isfahan and Chaharmahal va Bakhtiary provinces of Iran.
      MATERIALS AND METHODS: Animals in the field and those brought for slaughter at
      abattoirs were included. Blood samples were randomly collected from animals and
      investigated by polymerase chain reaction (PCR). RESULTS: T. gondii infections
      were detected in 0.00%, 6.60% and 17.9% of the sample cattle (n = 155), camels (n
      = 122) and sheep (n = 95) respectively. Sheep were more frequently affected in
      Chaharmahal va Bakhtiary (33.33%) compared to Isfahan (8.47%) (P = 0.005, 95%; CI
      = 6.88-43.35). No statistically significant difference was observed in infection
      prevalence between camels and sheep; and between the different sex categories in
      both camels and sheep. CONCLUSIONS: Evidence of T. gondii occurrence in sheep and
      camels was provided in the provinces under study. There is a need to investigate
      the potential risk factors of zoonotic infections. Furthermore, animal health and
      production losses caused by the parasite; and associated zoonotic implications in
      the area under study need to be explored.

PMID- 25371810
TI  - Evaluation of Gastric Lesions Based on Helicobacter pylori and Helicobacter-Like
      Organisms (HLOs) in Cats; A Histopathological and Bacteriological Study.
AB  - BACKGROUND: The lesions induced by Helicobacter pylori in a candidate animal
      model should always be examined thoroughly. The resemblance of these lesions to
      those observed in humans can indicate whether the usage of this model will
      contribute to the understanding of the various pathogenic mechanisms involved in
      the development of human H. pylori-associated diseases. OBJECTIVES: The aim of
      this study was to perform a histopathological and bacteriological evaluation of
      gastric lesions based on H. pylori and Helicobacter-like organisms (HLOs) in
      cats. MATERIALS AND METHODS: The present study was carried out on 28 cat's (13
      male and 15 female cases) gastric mucosae, which were tested by bacteriological
      and histopathological methods. Biochemical tests such as catalase, oxidase and
      urease were utilized in addition to Gram and Giemsa staining. RESULTS: This
      research demonstrated that solely one case of H. pylori was isolated by gastric
      mucosal culture. Microscopically, the infected stomachs by HLOs comprised a mild
      to severe diffuse lymphoplasmacytic infiltration into the subglandular and
      gastric mucosa. Lymphoid follicles were also marked, particularly within pyloric
      tissues and mostly in displaced mucosal glands. For 75% of the gastritis cases,
      both HLOs and rapid urease tests were positive, whereas 83% of cases were more
      than one-year-old with gastritis. Furthermore, 75% of cats indicated gastritis,
      though 25% encompassed no gastritis; hence 20% had negative results for the rapid
      urease test and 25% for the Giemsa staining test. Such results may indicate that
      cats without gastritis were considered as free of HLOs pathogenic bacteria.
      CONCLUSIONS: These results suggest that most cases of gastritis were located in
      the antral region. Additionally, the isolation of H. pylori from domestic cats
      raises the possibility of zoonotic characteristics for the slightly pathogen;
      therefore transmission occurs from cats to human and vice versa.

PMID- 25371811
TI  - Reduced beta connectivity during emotional face processing in adolescents with
      autism.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder
      characterized by impairments in social cognition. The biological basis of
      deficits in social cognition in ASD, and their difficulty in processing emotional
      face information in particular, remains unclear. Atypical communication within
      and between brain regions has been reported in ASD. Interregional phase-locking
      is a neurophysiological mechanism mediating communication among brain areas and
      is understood to support cognitive functions. In the present study we
      investigated interregional magnetoencephalographic phase synchronization during
      the perception of emotional faces in adolescents with ASD. METHODS: A total of 22
      adolescents with ASD (18 males, mean age =14.2 +/- 1.15 years, 22 right-handed)
      with mild to no cognitive delay and 17 healthy controls (14 males, mean age =14.4
      +/- 0.33 years, 16 right-handed) performed an implicit emotional processing task
      requiring perception of happy, angry and neutral faces while we recorded
      neuromagnetic signals. The faces were presented rapidly (80 ms duration) to the
      left or right of a central fixation cross and participants responded to a
      scrambled pattern that was presented concurrently on the opposite side of the
      fixation point. Task-dependent interregional phase-locking was calculated among
      source-resolved brain regions. RESULTS: Task-dependent increases in interregional
      beta synchronization were observed. Beta-band interregional phase-locking in
      adolescents with ASD was reduced, relative to controls, during the perception of
      angry faces in a distributed network involving the right fusiform gyrus and
      insula. No significant group differences were found for happy or neutral faces,
      or other analyzed frequency ranges. Significant reductions in task-dependent beta
      connectivity strength, clustering and eigenvector centrality (all P <0.001) in
      the right insula were found in adolescents with ASD, relative to controls.
      CONCLUSIONS: Reduced beta synchronization may reflect inadequate recruitment of
      task-relevant networks during emotional face processing in ASD. The right insula,
      specifically, was a hub of reduced functional connectivity and may play a
      prominent role in the inability to effectively extract emotional information from
      faces. These findings suggest that functional disconnection in brain networks
      mediating emotional processes may contribute to deficits in social cognition in
      this population.

PMID- 25371814
TI  - Long-term outcome after vitrectomy for macular edema with retinal vein occlusion
      dividing into the occlusion site.
AB  - Purpose. To investigate the efficacy of treatment for macular edema secondary to
      retinal vein occlusion (RVO) with vitrectomy. Methods. This retrospective study
      identified patients with macular edema associated with RVO between January 2004
      and April 2006. Inclusion criteria were eyes with (1) preoperative visual acuity
      (VA) of 20/40 or worse, (2) a central foveal thickness (CFT) greater than 250
      MUm, and (3) vitrectomy with internal limiting membrane and intravitreal
      triamcinolone acetonide. Each patient had their RVO classified as a major or
      macular BRVO or hemispheric RVO (HSRVO). Results. Forty-six eyes with major BRVO,
      18 eyes with macular BRVO, and 17 eyes with HSRVO were investigated. VA was
      significantly improved at 24 months after surgery for each group (P < 0.05).
      Vision in the macular BRVO group 24 months after surgery was significantly better
      than that in other groups (P < 0.05). For each group, a concomitant reduction of
      CFT was noted at every time point when compared to preoperative values (P <
      0.001). Conclusions. In macular BRVO, the postoperative vision 24 months after
      surgery was significantly better than the other groups. These findings suggest
      that additional and earlier treatments might be more important for patients with
      major BRVO and HSRVO than for those with macular BRVO. 

PMID- 25371812
TI  - Clinical and economic consequences of hospital-acquired resistant and multidrug
      resistant Pseudomonas aeruginosa infections: a systematic review and meta
      analysis.
AB  - BACKGROUND: Increasing rates of resistant and multidrug-resistant (MDR) P.
      aeruginosa in hospitalized patients constitute a major public health threat. We
      present a systematic review of the clinical and economic impact of this resistant
      pathogen. METHODS: Studies indexed in MEDLINE and Cochrane databases between
      January 2000-February 2013, and reported all-cause mortality, length of stay,
      hospital costs, readmission, or recurrence in at least 20 hospitalized patients
      with laboratory confirmed resistant P. aeruginosa infection were included. We
      accepted individual study definitions of MDR, and assessed study methodological
      quality. RESULTS: The most common definition of MDR was resistance to more than
      one agent in three or more categories of antibiotics. Twenty-three studies (7,881
      patients with susceptible P. aeruginosa, 1,653 with resistant P. aeruginosa, 559
      with MDR P. aeruginosa, 387 non-infected patients without P. aeruginosa) were
      analyzed. A random effects model meta-analysis was feasible for the endpoint of
      all-cause in-hospital mortality. All-cause mortality was 34% (95% confidence
      interval (CI) 27% - 41%) in patients with any resistant P. aeruginosa compared to
      22% (95% CI 14% - 29%) with susceptible P. aeruginosa. The meta-analysis
      demonstrated a > 2-fold increased risk of mortality with MDR P. aeruginosa
      (relative risk (RR) 2.34, 95% CI 1.53 - 3.57) and a 24% increased risk with
      resistant P. aeruginosa (RR 1.24, 95% CI 1.11 - 1.38), compared to susceptible P.
      aeruginosa. An adjusted meta-analysis of data from seven studies demonstrated a
      statistically non-significant increased risk of mortality in patients with any
      resistant P. aeruginosa (adjusted RR 1.24, 95% CI 0.98 - 1.57). All three studies
      that reported infection-related mortality found a statistically significantly
      increased risk in patients with MDR P. aeruginosa compared to those with
      susceptible P. aeruginosa. Across studies, hospital length of stay (LOS) was
      higher in patients with resistant and MDR P. aeruginosa infections, compared to
      susceptible P. aeruginosa and control patients. Limitations included
      heterogeneity in MDR definition, restriction to nosocomial infections, and
      potential confounding in analyses. CONCLUSIONS: Hospitalized patients with
      resistant and MDR P. aeruginosa infections appear to have increased all-cause
      mortality and LOS. The negative clinical and economic impact of these pathogens
      warrants in-depth evaluation of optimal infection prevention and stewardship
      strategies.

PMID- 25371813
TI  - The influence of aortoseptal angulation on provocable left ventricular outflow
      tract obstruction in hypertrophic cardiomyopathy.
AB  - OBJECTIVES: Aortoseptal angulation (AoSA) can predict provocable left ventricular
      outflow tract obstruction (LVOTO) in patients with symptomatic hypertrophic
      cardiomyopathy (HCM). Lack of a standardised measurement technique in HCM without
      the need for complex three-dimensional (3D) imaging limits its usefulness in
      routine clinical practice. This study aimed to validate a simple measurement of
      AoSA using 2D echocardiography and cardiac MR (CMR) imaging as a predictor of
      LVOTO. METHODS: We retrospectively assessed 160 patients with non-obstructive
      HCM, referred for exercise stress echocardiography. AoSA was measured using
      resting 2D echocardiography in all patients, and CMR in 29. Twenty-five controls
      with normal echocardiograms were used for comparison. RESULTS: Patients with HCM
      had a reduced AoSA compared with controls (113 degrees +/-12 vs 126 degrees +/
      6), p<0.0001. Sixty (38%) patients had provocable LVOTO, with smaller angles than
      non-obstructive patients (108 degrees +/-12 vs 116 degrees +/-12, p<0.0001).
      AoSA, degree of mitral valvular regurgitation and incomplete systolic anterior
      motion (SAM) were associated with peak left ventricular outflow tract gradient
      (r=0.508, p<0.0001). An angle <=100 degrees  had 27% sensitivity, 91% specificity
      and 59% positive predictive value for predicting provocable LVOTO. When combined
      with SAM, specificity was 99% and positive predictive value 88%. Intraclass
      correlation coefficient of AoSA measured by two observers was 0.901 (p<0.0001).
      Bland-Altman analysis of echocardiographic AoSA showed good agreement with the
      CMR-derived angle. CONCLUSIONS: Measurement of AoSA using echocardiography in HCM
      is easy, reproducible and comparable to CMR. Patients with provocable LVOTO have
      reduced angles compared with non-obstructive patients. AoSA is highly specific
      for provocable LVOTO and should prompt further evaluation in symptomatic patients
      without resting obstruction.

PMID- 25371815
TI  - Maternal weight gain in pregnancy and risk of obesity among offspring: a
      systematic review.
AB  - OBJECTIVES: To systematically review the evidence from prospective and
      retrospective cohort studies on the association between gestational weight gain
      (GWG) and offspring's body weight. METHODS: Electronic databases PubMed, Web of
      Science, CINAHL, and Academic Search Premiere were searched from inception
      through March 18, 2013. Included studies (n = 23) were English articles that
      examined the independent associations of GWG with body mass index (BMI) and/or
      overweight status in the offspring aged 2 to 18.9 years. Two authors
      independently extracted the data and assessed methodological quality of the
      included studies. RESULTS: Evidence from cohort studies supports that total GWG
      and exceeding the Institute of Medicine maternal weight gain recommendation were
      associated with higher BMI z-score and elevated risk of overweight or obesity in
      offspring. The evidence of high rate of GWG during early- and mid-pregnancy is
      suggestive. Additionally, the evidence on inadequate GWG and net GWG in relation
      to body weight outcomes in offspring is insufficient to draw conclusions.
      CONCLUSIONS: These findings suggest that GWG is a potential risk factor for
      childhood obesity. However, findings should be interpreted with caution due to
      measurement issues of GWG and potential confounding effects of shared familial
      characteristics (i.e., genetics and maternal and child's lifestyle factors).

PMID- 25371816
TI  - Barriers to lose weight from the perspective of children with overweight/obesity
      and their parents: a sociocultural approach.
AB  - INTRODUCTION: There are not enough studies about the barriers to lose weight from
      the perspective of children and their parents. METHODS: Children and adolescents
      diagnosed with overweight/obesity in the Department of Endocrinology and their
      parents were invited to participate in a series of focus group discussions (FGD).
      Twenty-nine children 10-16 years old and 22 parents participated in 7 focus
      groups; 2 mothers and 2 adolescents participated in depth interviews. All
      interviews were recorded, transcribed, and analyzed through grounded theory.
      RESULTS: Parents went to the hospital only when their children presented any
      obesity complication; for them, overweight was not a health problem. Parents
      referred to lack of time to supervise about a healthy diet and exercise; besides,
      the same parents, relatives, friends, and the mass media encourage the
      consumption of junk food. Children accepted eating a lot, not doing exercise,
      skipping meals, and not understanding overweight consequences. Both, parents and
      children, demanded support to do the time recommended for exercise inside the
      schools. They also suggested getting information from schools and mass media (TV)
      about overweight consequences, exercise, and healthy food by health workers; they
      recommended prohibiting announcements about junk food and its sale. CONCLUSIONS:
      The barriers detected were lack of perception of being overweight, its
      identification as a disease and its consequences, lack of time to supervise a
      healthy lifestyle, and a big social influence to eat junk food.

PMID- 25371817
TI  - Sex-related differences in the effects of the mediterranean diet on glucose and
      insulin homeostasis.
AB  - Objective. To document sex differences in the impact of the Mediterranean diet
      (MedDiet) on glucose/insulin homeostasis and to verify whether these sex-related
      effects were associated with changes in nonesterified fatty acids (NEFA).
      Methods. All foods were provided to 38 men and 32 premenopausal women (24-53 y)
      during 4 weeks. Variables were measured during a 180 min OGTT before and after
      the MedDiet. Results. A sex-by-time interaction for plasma insulin iAUC was found
      (men: -17.8%, P = 0.02; women: +9.4%, P = 0.63; P for sex-by-time interaction =
      0.005). A sex-by-time interaction was also observed for insulin sensitivity
      (Cederholm index, P = 0.03), for which only men experienced improvements (men:
      +8.1%, P = 0.047; women: -5.9%, P = 0.94). No sex difference was observed for
      glucose and C-peptide responses. Trends toward a decrease in NEFA AUC (P = 0.06)
      and an increase in NEFA suppression rate (P = 0.06) were noted, with no sex
      difference. Changes in NEFA were not associated with change in insulin
      sensitivity. Conclusions. Results suggest that the more favorable changes in
      glucose/insulin homeostasis observed in men compared to women in response to the
      MedDiet are not explained by sex differences in NEFA response. This clinical
      trial is registered with clinicaltrials.gov NCT01293344. 

PMID- 25371818
TI  - A body shape index and heart rate variability in healthy indians with low body
      mass index.
AB  - Background. One third of Indian population is said to be suffering from chronic
      energy deficiency (CED), with increased risk of developing chronic diseases. A
      new anthropometric measure called A Body Shape Index (ABSI) is said to be a
      better index in predicting risks for premature mortality. ABSI is also in part
      said to be a surrogate of visceral fat. Objective. The present study aimed to
      explore the association between indices of HRV (heart rate variability), BMI, WC,
      and ABSI in healthy Indian males with low BMI (BMI < 18.5 kg/m(2)) and to compare
      with normal BMI group (BMI 18.5 to 24.9 kg/m(2)). Methodology. ABSI and BMI were
      derived from anthropometric parameters, namely, height, weight, and waist
      circumference in 178 males aged 18 to 78 years. Subjects were categorized into
      two groups based on their BMI. Results and Conclusions. Power spectral analysis
      of HRV demonstrated a significant negative correlation between Log HF (high
      frequency) and ABSI in both low BMI [-24.2 (9.4), P < 0.05] and normal BMI group
      [-23.41 (10.1), P < 0.05] even after controlling for age. Thus even with slight
      increase in BMI among low BMI individuals, there could be a greater risk of
      cardiovascular morbidity and mortality. 

PMID- 25371819
TI  - Variability in the Management of Superficial Venous Thrombophlebitis across
      Practitioners Based in North America and the Global Community.
AB  - Introduction. This study aimed to compare management patterns of patients with
      SVT among healthcare practitioners based in North America versus those in the
      global community. Methods. A 17-question, multiple choice survey with questions
      regarding SVT diagnosis and management strategies was provided to practitioners
      who attended the American Venous Forum (AVF) meeting in 2011. Results. There were
      487 practitioners surveyed with 365 classified as North American (US or Canada)
      and 122 (56 Europe, 25 Asia, 11 South America, and 7 Africa) representing the
      global community. The key difference seen between the groups was in the initial
      imaging study used in patients presenting with SVT (P = 0.046) and physicians in
      the US ordered fewer bilateral duplex ultrasounds and more unilateral duplex
      ultrasounds (49.6% versus 58.2%, 39.7% versus 34.4%). In the US cohort,
      phlebologists and vascular surgeons constituted 82% (n = 300) of the specialties
      surveyed. In the global community, SVT was managed by phlebologists or vascular
      surgeons 44% (n = 54) of the time. Surgical management was highly variable
      between groups. Conclusion. There is currently no consensus between or among
      practitioners in North America or globally as to the surgical management of SVT,
      duration of follow-up, and anticoagulation parameters. 

PMID- 25371820
TI  - Signaling Network Map of Endothelial TEK Tyrosine Kinase.
AB  - TEK tyrosine kinase is primarily expressed on endothelial cells and is most
      commonly referred to as TIE2. TIE2 is a receptor tyrosine kinase modulated by its
      ligands, angiopoietins, to regulate the development and remodeling of vascular
      system. It is also one of the critical pathways associated with tumor
      angiogenesis and familial venous malformations. Apart from the vascular system,
      TIE2 signaling is also associated with postnatal hematopoiesis. Despite the
      involvement of TIE2-angiopoietin system in several diseases, the downstream
      molecular events of TIE2-angiopoietin signaling are not reported in any pathway
      repository. Therefore, carrying out a detailed review of published literature, we
      have documented molecular signaling events mediated by TIE2 in response to
      angiopoietins and developed a network map of TIE2 signaling. The pathway
      information is freely available to the scientific community through NetPath, a
      manually curated resource of signaling pathways. We hope that this pathway
      resource will provide an in-depth view of TIE2-angiopoietin signaling and will
      lead to identification of potential therapeutic targets for TIE2-angiopoietin
      associated disorders. 

PMID- 25371821
TI  - The influence of flanking secondary structures on amino Acid content and typical
      lengths of 3/10 helices.
AB  - We used 3D structures of a highly redundant set of bacterial proteins encoded by
      genes of high, average, and low GC-content. Four types of connecting bridges
      regions situated between any of two major elements of secondary structure (alpha
      helices and beta strands)-containing a pure random coil were compared with
      connecting bridges containing 3/10 helices. We included discovered trends in the
      original "VVTAK Connecting Bridges" algorithm, which is able to predict more
      probable conformation for a given connecting bridge. The highest number of
      significant differences in amino acid usage was found between 3/10 helices
      containing bridges connecting two beta strands (they have increased Phe, Tyr,
      Met, Ile, Leu, Val, and His usages but decreased usages of Asp, Asn, Gly, and
      Pro) and those without 3/10 helices. The typical (most common) length of 3/10
      helices situated between two beta strands and between beta strand and alpha helix
      is equal to 5 amino acid residues. The preferred length of 3/10 helices situated
      between alpha helix and beta strand is equal to 3 residues. For 3/10 helices
      situated between two alpha helices, both lengths (3 and 5 amino acid residues)
      are typical. 

PMID- 25371822
TI  - Improving quality of life in nursing homes: the structured resident interview
      approach.
AB  - The quality of life (QOL) of the approximately 1.5 million nursing facility (NF)
      residents in the US is undoubtedly lower than desired by residents, families,
      providers, and policy makers. Although there have been important advances in
      defining and measuring QOL for this population, there is a need for interventions
      that are tied to standardized measurement and quality improvement programs. This
      paper describes the development and testing of a structured, tailored assessment
      and care planning process for improving the QOL of nursing home residents. The
      Quality of Life Structured Resident Interview and Care Plan (QOL.SRI/CP) builds
      on a decade of research on measuring QOL and is designed to be easily implemented
      in any US nursing home. The approach was developed through extensive and
      iterative pilot testing and then tested in a randomized controlled trial in three
      nursing homes. Residents were randomly assigned to receive the assessment alone
      or both the assessment and an individualized QOL care plan task. The results show
      that residents assigned to the intervention group experienced improved QOL at 90-
      and 180-day follow-up, while QOL of residents in the control group was unchanged.

PMID- 25371823
TI  - Improved Rifamycin B Production by Nocardia mediterranei MTCC 14 under Solid
      State Fermentation through Process Optimization.
AB  - Optimization of various production parameters using response surface methodology
      (RSM) was performed to assess maximum yield of rifamycin B from Nocardia
      mediterranei MTCC 14. Plackett-Burman design test was applied to determine the
      significant effects of various production parameters such as glucose, maltose,
      ribose, galactose, beef extract, peanut meal, ammonium chloride, ammonium
      sulphate, barbital, pH, and moisture content on production of rifamycin B. Among
      the eleven variables tested, galactose, ribose, glucose, and pH were found to
      have significant effect on rifamycin B production. Optimum levels of the
      significant variables were decided by using a central composite design. The most
      appropriate condition for production of rifamycin B was found to be a single step
      production at galactose (8% w/w), ribose (3% w/w), glucose (9% w/w), and pH
      (7.0). At these optimum production parameters, the maximum yield of rifamycin B
      obtained experimentally (9.87 g/kgds dry sunflower oil cake) was found to be very
      close to its predicted value of 10.35 g/kgds dry sunflower oil cake. The
      mathematical model developed was found to fit greatly with the experimental data
      of rifamycin B production. 

PMID- 25371824
TI  - Analysis of occlusal vertical dimension and mandibular Basal bone height in a
      nigerian population.
AB  - Background. The actual basal bone height of the reconstructed mandible is
      relevant to achieve normal occlusal vertical dimension for the prosthesis
      fabricated. The purpose of the study was to determine the mean and baseline
      values of the occlusal vertical dimension and height of the mandibular basal bone
      in a Nigerian population. Method. Each participant was asked to bring the upper
      and lower teeth into contact, while the distance between the nasal sill and
      dimple on the lower lip was measured (OVD). The skin at lower border of the
      mandible was marked and the distance between this point and the landmark on the
      lower lip was measured, MBH. Result. 200 subjects were evaluated. Age range was
      16-30 years, mean +/- (SD), 21.6 +/- (3.1) years. Males had mean +/- (SD) of
      42.10 +/- (5.34) mm for OVD and females 39.72 +/- (5.25) mm; acceptable baseline
      range of OVD for any population will be 34-48 mm (3.4-4.8) cm. All the males had
      a mean +/- (SD), 30.54 +/- (6.13) mm for MBH, and all the females 29.63 +/-
      (5.23) mm. Acceptable baseline range of MBH for any population will be 24-37 mm
      (2.4-3.7) cm. Conclusion. To reconstruct the mandible and still maintain the OVD,
      heights of bone grafts must not be less than 2 cm or greater than 4 cm. 

PMID- 25371825
TI  - The Signature Sequence Region of the Human Drug Transporter Organic Anion
      Transporting Polypeptide 1B1 Is Important for Protein Surface Expression.
AB  - The organic anion transporting polypeptides (OATPs) encompass a family of
      membrane transport proteins responsible for the uptake of xenobiotic compounds.
      Human organic anion transporting polypeptide 1B1 (OATP1B1) mediates the uptake of
      clinically relevant compounds such as statins and chemotherapeutic agents into
      hepatocytes, playing an important role in drug delivery and detoxification. The
      OATPs have a putative 12-transmembrane domain topology and a highly conserved
      signature sequence (human OATP1B1: DSRWVGAWWLNFL), spanning the extracellular
      loop 3/TM6 boundary. The presence of three conserved tryptophan residues at the
      TM interface suggests a structural role for the sequence. This was investigated
      by site-directed mutagenesis of selected amino acids within the sequence D251E,
      W254F, W258/259F, and N261A. Transport was measured using the substrate estrone-3
      sulfate and surface expression detected by luminometry and confocal microscopy,
      facilitated by an extracellular FLAG epitope. Uptake of estrone-3-sulfate and the
      surface expression of D251E, W254F, and W258/259F were both significantly reduced
      from the wild type OATP1B1-FLAG in transfected HEK293T cells. Confocal microscopy
      revealed that protein was produced but was retained intracellularly. The uptake
      and expression of N261A were not significantly different. The reduction in
      surface expression and intracellular protein retention indicates a structural
      and/or membrane localization role for these signature sequence residues in the
      human drug transporter OATP1B1. 

PMID- 25371826
TI  - Preparation and characterization of liquisolid compacts for improved dissolution
      of telmisartan.
AB  - The objective of the present work was to obtain pH independent and improved
      dissolution profile for a poorly soluble drug, telmisartan using liquisolid
      compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle,
      Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations
      were evaluated for drug excipient interactions, change in crystallinity of drug,
      flow properties, and general quality control tests of tablets using Fourier
      transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC),
      X-ray diffraction (XRD), angle of repose, and various pharmacopoeial tests. In
      vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and
      7.4). Stability studies were performed at 40 degrees C and 75% RH for three
      months. The formulation was found to comply with Indian pharmacopoeial limits for
      tablets. FTIR studies confirmed no interaction between drug and excipients. XRD
      and DSC studies indicate change/reduction in crystallinity of drug. Dissolution
      media were selected based on the solubility studies. The optimized formulation
      showed pH independent release profile with significant improvement (P < 0.005) in
      dissolution compared to plain drug and conventional marketed formulation. No
      significant difference was seen in the tablet properties, and drug release
      profile after storage for 3 months. 

PMID- 25371827
TI  - Increasing Resistance of Coagulase-Negative Staphylococci in Total Hip
      Arthroplasty Infections: 278 THA-Revisions due to Infection Reported to the
      Norwegian Arthroplasty Register from 1993 to 2007.
AB  - We investigated bacterial findings from intraoperative tissue samples taken
      during revision due to infection after total hip arthroplasty (THA). The aim was
      to investigate whether the susceptibility patterns changed during the period from
      1993 through 2007. Reported revisions due to infection in the Norwegian
      Arthroplasty Register (NAR) were identified, and 10 representative hospitals in
      Norway were visited. All relevant information on patients reported to the NAR for
      a revision due to infection, including bacteriological findings, was collected
      from the medical records. A total of 278 revision surgeries with bacterial growth
      in more than 2 samples were identified and included. Differences between three 5
      year time periods were tested by the chi-square test for linear trend. The most
      frequent isolates were coagulase-negative staphylococci (CoNS) (41%, 113/278) and
      Staphylococcus aureus (19%, 53/278). The proportion of CoNS resistant to the
      methicillin-group increased from 57% (16/28) in the first period, 1993-1997, to
      84% (52/62) in the last period, 2003-2007 (P = 0.003). There was also significant
      increase in resistance for CoNS to cotrimoxazole, quinolones, clindamycin, and
      macrolides. All S. aureus isolates were sensitive to both the methicillin-group
      and the aminoglycosides. For the other bacteria identified no changes in
      susceptibility patterns were found. 

PMID- 25371828
TI  - Surgical and orthodontic management of fused maxillary central and lateral
      incisors in early mixed dentition stage.
AB  - Fusion is one of the developmental dental anomalies in which two adjacent teeth
      are joined at the crown level forming a single tooth with an enlarged crown.
      Fusion causes some clinical problems such as unaesthetic appearance, pain,
      caries, and malocclusion. The management of fusion often needs multidisciplinary
      approach to give best possible esthetic and functional outcome. This paper
      reports a case of 9-year-old boy with fused maxillary left central and lateral
      incisors who was treated with 2 * 4 fixed orthodontic appliances after surgical
      separation of fused teeth. 

PMID- 25371829
TI  - Photodynamic therapy in pediatric dentistry.
AB  - Conservation of deciduous teeth with pulp alterations caused by caries and trauma
      is a major therapeutic challenge in pediatric dentistry as a result of the
      internal anatomy and life cycle characteristic. It is essential that the root
      canal procedures sanitizers have a performance in eliminating bacterial. In this
      context, antimicrobial photodynamic therapy (PAT) is promising and emerging as
      adjuvant therapy in an attempt to eliminate the microorganisms persistent to
      chemi-mechanical preparation. Since there is presence of oxygen in cells,
      photosensitizer activated by light can react with molecules in its vicinity by
      electrons' or hydrogen's transfer, leading to microorganism death. This paper
      reports the case of 4-year-old patient, female, with early childhood caries. The
      proposed endodontic treatment incuded chemomechanical treatment allied to PAT in
      the decontamination of root canals using methylene blue dye 50 MUg/mL during 3-5
      minutes and 40 J/cm(2) as energy density, taking into account the need for tissue
      penetration and effectiveness of PAT inside the dentinal tubules. 

PMID- 25371830
TI  - Crusted demodicosis in an immunocompetent pediatric patient.
AB  - Demodicosis refers to the infestation by Demodex spp., a saprophytic mite of the
      pilosebaceous unit. Demodex proliferation can result in a number of cutaneous
      disorders including pustular folliculitis, pityriasis folliculorum,
      papulopustular, and granulomatous rosacea, among others. We report the case of a
      7-year-old female presenting with pruritic grayish crusted lesions over her nose
      and cheeks, along with facial erythema, papules, and pustules. The father
      referred chronic use of topical steroids. A potassium hydroxide mount of a
      pustule scraping revealed several D. folliculorum mites. Oral ivermectin (200
      MUg/kg, single dose) plus topical permethrin 5% lotion applied for 3 consecutive
      nights were administered. Oral ivermectin was repeated every week and oral
      erythromycin plus topical metronidazole cream was added. The facial lesions
      greatly improved within the following 3 months. While infestation of the
      pilosebaceous unit by Demodex folliculorum mites is common, only few individuals
      present symptoms. Demodicosis can present as pruritic papules, pustules, plaques,
      and granulomatous facial lesions. To our knowledge, this is the first reported
      case of facial crusted demodicosis in an immunocompetent child. The development
      of symptoms in this patient could be secondary to local immunosuppression caused
      by the chronic use of topical steroids. 

PMID- 25371831
TI  - Spontaneous cervical epidural hematoma with hemiparesis mimicking cerebral
      stroke.
AB  - Aim. Spontaneous cervical epidural hematoma (SCEH) is defined as an epidural
      hematoma that does not have an etiological explanation. The most common site for
      SCEH is cervicothoracic area. Early diagnosis and treatment are important for
      prognosis and good results. In this paper, we aimed to present a case who
      complains of sudden weakness on right extremities imitating cerebral stroke and
      that neuroimaging reveals spontaneous cervical epidural hematoma. Case. A 72-year
      old woman was admitted to our hospital with acute neck pain and loss of strength
      on right extremities. On neurological examination, the patient had right
      hemiparesis. PT, aPTT, and INR results were 50.5, 42.8, and 4.8, respectively.
      Cranial MRI was in normal limits. Spinal MRI revealed a lesion that extends from
      C4 to C7 located on the right side and compatible with epidural hematoma. The
      patient was operated after normalization of INR values. Conclusion. Even though
      SCEH is a rare condition, it can cause severe morbidity and mortality. Early
      diagnosis and treatment are quiet important for prognosis. SCEH can easily be
      mistaken for stroke as with other pathologies and this diagnosis should come to
      mind especially in patients who have diathesis of bleeding. 

PMID- 25371832
TI  - Intermittent brugada syndrome presenting with syncope in an adult female.
AB  - Background. Brugada syndrome accounts for 4-12% of all sudden deaths worldwide
      and at least 20% of sudden deaths in patients with structurally normal hearts.
      Case Report. A 48-year-old female presented to the emergency department after two
      witnessed syncopal episodes. While awaiting discharge had a third collapse
      followed by cardiac arrest with shockable rhythm. Initial electrocardiogram
      showed wide QRS complex with left axis deviation, ST-segment elevation of <1 mm
      in V1 and V2, and flattening of T waves in V1. The angiogram did not demonstrate
      obstructive coronary disease. The electrocardiogram obtained two days after these
      events showed a right bundle branch block with ST-segment elevation of >2 mm
      followed by a negative T wave with no isoelectric separation, suggestive of
      spontaneous intermittent Brugada type 1 pattern. Cardiac magnetic resonance
      imaging demonstrated neither structural heart disease nor abnormal myocardium.
      After placement of an implantable cardioverter defibrillator the patient was
      discharged. Why should an emergency physician be aware of this? Brugada syndrome
      is an infrequently encountered clinical entity which may have a fatal outcome.
      This syndrome primarily presents with syncope. It should be considered as a
      component of differential diagnosis in patients with family history of syncope
      and sudden cardiac death. 

PMID- 25371833
TI  - Self-expandable metal stent placement for closure of a leak after total
      gastrectomy for gastric cancer: report on three cases and review of the
      literature.
AB  - In the setting of the curative oncological surgery, the gastric surgery is
      exposed to complicated upper gastrointestinal leaks, and consequently the
      management of this problem has become more critically focused than was previously
      possible. We report here three cases of placement of a partially silicone-coated
      SEMS (Evolution Controlled Release Esophageal Stent System, Cook Medical, Winston
      Salem, NC, USA) in patients who underwent total gastrectomy with Roux-en-Y end-to
      side esophagojejunostomy for a gastric adenocarcinoma. The promising results of
      our report, despite the small number of patients, suggest that early stenting
      (through a partially silicone-coated SEMS) is a feasible alternative to surgical
      treatment in this subset of patients. In fact, in the treatment of leakage after
      total gastrectomy, plastic stents and totally covered metallic stents may not
      adhere sufficiently to the esophagojejunal walls and, as a result, migrate beyond
      the anastomosis. However, prospective studies with a larger number of patients
      might assess the real effectiveness and safety of this procedure. 

PMID- 25371834
TI  - Cutaneous Vasculitis, Interstitial Pneumonia with Crazy-Paving Appearance, and
      Positive pANCA in a Patient with Severe Crohn's Disease.
AB  - Cutaneous vasculitis, interstitial pneumonia with crazy-paving appearance on high
      resolution computed tomography, and repeated positive perinuclear anti-neutrophil
      cytoplasmic antibodies (pANCA) are rarely found together in patients with
      inflammatory bowel disease in the existing literature. We report the case of a
      Chinese patient previously diagnosed with cutaneous vasculitis and interstitial
      pneumonia, who presented with acute pain and mass in his right lower quadrant a
      couple of years later. The terminal ileum biopsy and postoperative pathology
      confirmed Crohn's disease (CD). 

PMID- 25371835
TI  - A Jehovah's Witness with Acute Myeloid Leukemia Successfully Treated with an
      Epigenetic Drug, Azacitidine: A Clue for Development of Anti-AML Therapy
      Requiring Minimum Blood Transfusions.
AB  - Therapy for acute leukemia in Jehovah's Witnesses patients is very challenging
      because of their refusal to accept blood transfusions, a fundamental supportive
      therapy for this disease. These patients are often denied treatment for fear of
      treatment-related death. We present the first Jehovah's Witness patient with
      acute myeloid leukemia (AML) treated successfully with azacitidine. After
      achieving complete remission (CR) with one course of azacitidine therapy, the
      patient received conventional postremission chemotherapy and remained in CR. In
      the case of patients who accept blood transfusions, there are reports indicating
      the treatment of AML patients with azacitidine. In these reports, azacitidine
      therapy was less toxic, including hematoxicity, compared with conventional
      chemotherapy. The CR rate in azacitidine-treated patients was inadequate;
      however, some characteristics could be useful in predicting azacitidine
      responders. The present case is useful for treating Jehovah's Witnesses patients
      with AML and provides a clue for anti-AML therapy requiring minimum blood
      transfusions. 

PMID- 25371836
TI  - Community Acquired Chronic Arthritis due to Pseudomonas aeruginosa in a
      Previously Healthy Pregnant Woman.
AB  - Septic arthritis caused by Pseudomonas aeruginosa is uncommon in the
      immunocompetent population, despite its occurrence in younger patients with open
      injuries and in intravenous drug abusers. Here we report a case of septic
      arthritis caused by P. aeruginosa. This case is unique for several reasons.
      First, it is a case of septic arthritis in a pregnant woman with no traditional
      risk factors reported in the literature including history of prior traumatic
      events, hospitalisation, or chronic underlying disease. She was suspected of
      having transient osteoporosis associated with pregnancy to involve both hip
      joints. Second, this is the first reported case of a community acquired chronic
      septic arthritis due to P. aeruginosa involving large joints of both upper and
      lower extremities. The patient was treated successfully with a combination of
      ceftazidime and amikacin for 4 weeks followed by oral ciprofloxacin 750 mg twice
      daily for 8 weeks. 

PMID- 25371837
TI  - A case of misdiagnosed cesarean scar pregnancy with a viable birth at 28 weeks.
AB  - We report our experience with a case of presumptive cesarean scar pregnancy,
      based on detection of a gestational sac (GS) in early pregnancy at the site of a
      previous cesarean scar. The GS grew into the uterine cavity as the pregnancy
      progressed, showing an ultrasound image similar to that of a normal pregnancy.
      Thus, the pregnancy continued, resulting in a viable birth at 28 weeks of
      gestation. Cesarean scar pregnancy is classified as myometrial implantation or
      implantation growth into the uterine cavity. In the latter type, the gestational
      sac moves upward with increasing gestational weeks and it shows the same
      ultrasound image as a normal pregnancy. Therefore, the diagnosis must be made in
      the early pregnancy. 

PMID- 25371838
TI  - Surgical management of massive labial edema in a gravid preeclamptic diabetic.
AB  - Background. Massive labial edema is a rare complication during pregnancy that can
      jeopardize vaginal delivery, as well as leading to maternal and fetal morbidity.
      It can be related to systemic pathologies, but has been commonly associated with
      preeclampsia and diabetes. This increased and sometimes longstanding pressure may
      result in a "labial compartment syndrome" leading to microvascular damage and
      tissue necrosis if not resolved in a timely fashion. Case. Massive labial edema
      was treated first conservatively and then surgically in a gravid diabetic patient
      with severe preeclampsia. Immediately after Cesarean section, the labial
      compartment syndrome was relieved surgically and resolved rapidly. Conclusion.
      When conservative attempts at management of labial edema fail, or rapid
      resolution is critical to maternal and fetal outcome, surgical alternatives
      should be considered. 

PMID- 25371839
TI  - Subcutaneous Rupture of the Extensor Pollicis Longus Tendon after Corticosteroid
      Injections for DeQuervain's Stenosing Tenovaginitis.
AB  - DeQuervain's stenosing tenovaginitis is a common condition. Nonsurgical treatment
      by corticosteroid injection has significantly improved the management of this
      disease. The authors describe a case of subcutaneous rupture of the extensor
      pollicis longus tendon at the wrist, three months after two corticosteroid
      injections for DeQuervain's stenosing tenovaginitis. The etiological history has
      not found any trauma history of the wrist. The aim of our work is to draw
      attention to this rare complication and discuss its therapeutic management. Our
      functional results were excellent. 

PMID- 25371840
TI  - Six-Digit CPK and Mildly Affected Renal Function in McArdle Disease.
AB  - A previously healthy, white 12-year-old girl presented with diffuse body aches
      and poor perfusion. She developed severe respiratory failure and marked
      rhabdomyolysis and was mechanically ventilated. Although her CPK peaked at
      500,000 IU/L, her renal function was mildly affected and her creatinine did not
      exceed the 0.8 mg/dL. The rhabdomyolysis was gradually resolved following
      aggressive fluid hydration. The patient did not require dialysis and made a
      complete recovery. Genetic studies revealed the diagnosis of McArdle disease. 

PMID- 25371841
TI  - Autoimmune Gastrointestinal Paralysis: Failure of Conventional Treatment without
      Immunomodulation.
AB  - The treatment of the rare enteric nervous system (ENS) manifestations of
      paraneoplastic syndromes, which are most frequently associated with small cell
      lung cancer (SCLC), is poorly understood and described. Patients with
      neuroendocrine-derived tumors can develop B-cell reactivity towards the tumor
      with cross-reactivity for neurons located in the submucosal and myenteric ganglia
      of the ENS. The ensuing autoimmune neuritis causes aperistalsis and severe
      gastrointestinal (GI) dysfunction. Immune-directed therapy is not the standard of
      care but may be paramount for patient recovery. Our patient, a 63-year-old man
      with recent symptoms of esophageal dysmotility and newly diagnosed SCLC was
      hospitalized with nausea, emesis, and constipation. After an extensive work-up
      that included laparoscopy and celiotomy with bowel resection, we diagnosed what
      we refer to as Autoimmune Paraneoplastic Chronic Intestinal Pseudoobstruction (AP
      CIPO). Unlike the few clinically similar reports, SCLC and AP-CIPO were diagnosed
      in our patient within weeks of each other, which presented the dilemma of
      treating the two processes simultaneously. In this report, we review the relevant
      literature and describe our patient's course. We believe standard chemotherapy is
      not effective treatment for AP-CIPO. Based on evidence discussed herein, we
      suggest initiating autoimmune-directed therapy before or simultaneous with cancer
      directed therapy. 

PMID- 25371842
TI  - Intestinal malrotation: a rare cause of small intestinal obstruction.
AB  - Background. The diagnosis of intestinal malrotation is established by the age of
      1 year in most cases, and the condition is seldom seen in adults. In this paper,
      a patient with small intestinal malrotation-type intraperitoneal hernia who
      underwent surgery at an older age because of intestinal obstruction is presented.
      Case. A 73-year-old patient who presented with acute intestinal obstruction
      underwent surgery as treatment. Distended jejunum and ileum loops surrounded by a
      peritoneal sac and located between the stomach and transverse colon were
      determined. The terminal ileum had entered into the transverse mesocolon from the
      right lower part, resulting in kinking and subsequent segmentary obstruction. The
      obstruction was relieved, and the small intestines were placed into their normal
      position in the abdominal cavity. Conclusion. Small intestinal malrotations are
      rare causes of intestinal obstructions in adults. The appropriate treatment in
      these patients is placement of the intestines in their normal positions. 

PMID- 25371843
TI  - Random Whole Body Vibration over 5 Weeks Leads to Effects Similar to Placebo: A
      Controlled Study in Parkinson's Disease.
AB  - Background. Random whole body vibration (WBV) training leads to beneficial short
      term effects in patients with Parkinson's disease (PD). However, the effect of
      WBV lasting several weeks is not clear. Objectives. The aim of this study was to
      assess a random WBV training over 5 weeks in PD. Methods. Twenty-one participants
      with PD were allocated to either an experimental or a placebo group matched by
      age, gender, and Hoehn&Yahr stage. The WBV training consisted of 5 series, 60 s
      each. In the placebo group, vibration was simulated. The primary outcome was the
      change of performance in Functional reach test (FRT), step-walk-turn task,
      biomechanical Gait Analysis, Timed up and go test (TUG), and one leg stance.
      Findings. In most of the parameters, there was no significant interaction of
      "time*group." Both groups improved significantly in Gait parameters, TUG, and one
      leg stance. Only in the FRT [F(1,15) = 8.397; P < 0.05] and in the TUG [F(1,15) =
      4.971; P < 0.05] the experimental group performed significantly better than the
      placebo group. Conclusions. Random WBV training over 5 weeks seems to be less
      effective than reported in previous studies performing short-term training. The
      slight improvements in the FRT and TUG are not clinically relevant. 

PMID- 25371844
TI  - A Stability-Indicating HPLC-DAD Method for Determination of Stiripentol:
      Development, Validation, Kinetics, Structure Elucidation and Application to
      Commercial Dosage Form.
AB  - A rapid, simple, sensitive, and accurate isocratic reversed-phase stability
      indicating high performance liquid chromatography method has been developed and
      validated for the determination of stiripentol and its degradation product in its
      bulk form and pharmaceutical dosage form. Chromatographic separation was achieved
      on a Symmetry C18 column and quantification was achieved using photodiode array
      detector (DAD). The method was validated in accordance with the ICH requirements
      showing specificity, linearity (r (2) = 0.9996, range of 1-25 MUg/mL), precision
      (relative standard deviation lower than 2%), accuracy (mean recovery 100.08 +/-
      1.73), limits of detection and quantitation (LOD = 0.024 and LOQ = 0.081 MUg/mL),
      and robustness. Stiripentol was subjected to various stress conditions and it has
      shown marked stability under alkaline hydrolytic stress conditions, thermal,
      oxidative, and photolytic conditions. Stiripentol degraded only under acidic
      conditions, forming a single degradation product which was well resolved from the
      pure drug with significantly different retention time values. This degradation
      product was characterized by (1)H-NMR and (13)C-NMR spectroscopy as well as ion
      trap mass spectrometry. The results demonstrated that the method would have a
      great value when applied in quality control and stability studies for
      stiripentol. 

PMID- 25371845
TI  - Development of a univariate membrane-based mid-infrared method for protein
      quantitation and total lipid content analysis of biological samples.
AB  - Biological samples present a range of complexities from homogeneous purified
      protein to multicomponent mixtures. Accurate qualification of such samples is
      paramount to downstream applications. We describe the development of an MIR
      spectroscopy-based analytical method offering simultaneous protein quantitation
      (0.25-5 mg/mL) and analysis of total lipid or detergent species, as well as the
      identification of other biomolecules present in biological samples. The method
      utilizes a hydrophilic PTFE membrane engineered for presentation of aqueous
      samples in a dried format compatible with fast infrared analysis. Unlike
      classical quantification techniques, the reported method is amino acid sequence
      independent and thus applicable to complex samples of unknown composition. By
      comparison to existing platforms, this MIR-based method enables direct
      quantification using minimal sample volume (2 uL); it is well-suited where repeat
      access and limited sample size are critical parameters. Further, accurate results
      can be derived without specialized training or knowledge of IR spectroscopy.
      Overall, the simplified application and analysis system provides a more cost
      effective alternative to high-throughput IR systems for research laboratories
      with minimal throughput demands. In summary, the MIR-based system provides a
      viable alternative to current protein quantitation methods; it also uniquely
      offers simultaneous qualification of other components, notably lipids and
      detergents. 

PMID- 25371846
TI  - Content Determination of Active Component in Huangqi Yinyanghuo Group and Its
      Effects on hTERT and Bcl-2 Protein in Osteosarcoma.
AB  - To screen the optimal extraction process and content determination of active
      component of Huangqi Yinyanghuo group (HYG) and to study the effects of HYG on
      human telomerase reverse transcriptase (hTERT) and Bcl-2 protein in osteosarcoma
      (HOS) cells, providing the theoretical basis for clinical application of HYG in
      treatment of osteosarcoma, orthogonal design table L9(4(3)) was used to design
      the extraction process of HYG, and icariin was taken as the investigation index
      to optimize the extraction process of HYG. 0.125, 0.25, 0.5, 1, 2, 4, and 8
      MUmol/L HYG were taken to act separately on logarithmic growth phase osteosarcoma
      HOS cells, CCK-8 assay was used to determine cell viability, and
      immunohistochemical SP assay was used to determine the expression of hTERT and
      Bcl-2 protein. Apoptosis rate was positively correlated with the dose of HYG, and
      the expressions of hTERT and Bcl-2 protein were significantly decreased with the
      prolonged duration of action. Under the effect of HYG, dose was negatively
      correlated with osteosarcoma cell survival fraction; osteosarcoma cell survival
      fraction was positively correlated with hTERT and Bcl-2 protein; duration of
      action was negatively correlated with hTERT and Bcl-2 protein; and hTERT and Bcl
      2 protein were in a synchronous relationship. 

PMID- 25371847
TI  - Primary melanocytic tumors of the central nervous system: Report of two cases and
      review of literature.
AB  - BACKGROUND: Primary melanocytic tumors of the central nervous system (CNS)
      represent only 1% of all melanomas. We report two rare cases of primary diffuse
      leptomeningeal melanomatosis (PDLM; case 1) and primary melanoma of the thoraco
      lumbar spine (case 2). CASE DESCRIPTION: In case 1, multiple cerebrospinal fluid
      (CSF) studies and a brain biopsy were non-diagnostic, with a biopsy of the cauda
      equina eventually demonstrating malignant melanomatosis. Diagnosis of primary
      spinal cord melanoma was more straightforward in case 2 with imaging and biopsy.
      CONCLUSION: PDLM and primary intramedullary spinal melanoma are rare variants of
      primary CNS melanoma. This report contrasts the diagnostic challenges between the
      two entities and alerts the neurosurgeon into considering the diagnosis with
      appropriate clinical presentation.

PMID- 25371848
TI  - Symptomatic de novo arteriovenous malformation in an adult: Case report and
      review of the literature.
AB  - BACKGROUND: Cerebral arteriovenous malformations (AVMs) have been long thought to
      be a congenital anomaly of vasculogenesis in which arteries and veins form direct
      connections forming a vascular nidus without an intervening capillary bed or
      neural tissue. Scattered case reports have described that AVMs may form de novo
      suggesting they can become an acquired lesion. CASE DESCRIPTION: The current case
      report describes a patient who presented with new-onset seizures with an initial
      negative magnetic resonance imaging (MRI) of the brain and subsequently developed
      an AVM on a MRI 9 years later. CONCLUSION: This case joins a small, but growing
      body of literature that challenges the notion that all AVMs are congenital.

PMID- 25371849
TI  - Medical errors in neurosurgery.
AB  - BACKGROUND: Medical errors cause nearly 100,000 deaths per year and cost billions
      of dollars annually. In order to rationally develop and institute programs to
      mitigate errors, the relative frequency and costs of different errors must be
      documented. This analysis will permit the judicious allocation of scarce
      healthcare resources to address the most costly errors as they are identified.
      METHODS: Here, we provide a systematic review of the neurosurgical literature
      describing medical errors at the departmental level. Eligible articles were
      identified from the PubMed database, and restricted to reports of recognizable
      errors across neurosurgical practices. We limited this analysis to cross
      sectional studies of errors in order to better match systems-level concerns,
      rather than reviewing the literature for individually selected errors like wrong
      sided or wrong-level surgery. RESULTS: Only a small number of articles met these
      criteria, highlighting the paucity of data on this topic. From these studies,
      errors were documented in anywhere from 12% to 88.7% of cases. These errors had
      many sources, of which only 23.7-27.8% were technical, related to the execution
      of the surgery itself, highlighting the importance of systems-level approaches to
      protecting patients and reducing errors. CONCLUSIONS: Overall, the magnitude of
      medical errors in neurosurgery and the lack of focused research emphasize the
      need for prospective categorization of morbidity with judicious attribution.
      Ultimately, we must raise awareness of the impact of medical errors in
      neurosurgery, reduce the occurrence of medical errors, and mitigate their
      detrimental effects.

PMID- 25371850
TI  - Nutrition and Chronic Wounds.
AB  - Significance: Nutrition is one of the most basic of medical issues and is often
      ignored as a problem in the management of our chronic wound patients.
      Unfortunately, malnutrition is widespread in our geriatric patients even in
      nursing homes in developed countries. Attention to basic nutrition and providing
      appropriate supplements may assist in the healing of our chronic wounds. Recent
      Advances: Recent research has revealed the epidemiology of malnutrition in
      developed countries, the similarities to malnutrition in developing countries,
      and some of the physiologic and sociologic causes for this problem. More
      information is now available on the biochemical effects of nutrient deficiency
      and supplementation with macronutrients and micronutrients. In some cases,
      administration of isolated nutrients beyond recommended amounts for healthy
      individuals may have a pharmacologic effect to help wounds heal. Critical Issues:
      Much of the knowledge of the nutritional support of chronic wounds is based on
      information that has been obtained from trauma management. Due to the demographic
      differences of the patients and differences in the physiology of acute and
      chronic wounds, it is not logical to assume that all aspects of nutritional
      support are identical in these patient groups. Before providing specific
      nutritional supplements, appropriate assessments of patient general nutritional
      status and the reasons for malnutrition must be obtained or specific nutrient
      supplementation will not be utilized. Future Directions: Future research must
      concentrate on the biochemical and physiologic differences of the acute and
      chronic wounds and the interaction with specific supplements, such as
      antioxidants, vitamin A, and vitamin D.

PMID- 25371851
TI  - Role of Arginine and Omega-3 Fatty Acids in Wound Healing and Infection.
AB  - Significance: Only a few decades ago, the primary focus of nutritional
      supplementation was to prevent deficiencies of essential nutrients. It is now
      recognized that, at higher than essential levels, selected nutrients can have a
      pharmacologic effect to prevent or treat disease. Recent Advances: Two of the
      most important pharmaconutrients, arginine, and the omega-3 polyunsaturated fatty
      acids in fish oil, have been shown to have profound effects on wound healing and
      infections. Critical Issues: Both arginine and fish oils have independent
      benefits, but the combination appears to be much more effective. This combination
      has been shown to affect outcomes involving wound healing and infections, as
      reviewed here, and can also affect incidence and outcomes in cardiovascular
      disease, diabetes, organ transplant rejection, and other inflammatory conditions.
      These possibilities have not yet progressed to widespread clinical application.
      Future Directions: The optimal combinations of immunonutrients, timing of
      administration, and the doses needed for best results need to be determined in
      preclinical and clinical studies. Also, the mechanisms involved in the
      administration of pharmaconutrients need to be established.

PMID- 25371852
TI  - Micronutrients, Arginine, and Glutamine: Does Supplementation Provide an
      Efficient Tool for Prevention and Treatment of Different Kinds of Wounds?
AB  - Significance: Wound-healing complications are a clinical problem with a
      considerable socioeconomic burden. Since several nutrients play a physiological
      role in wound healing, supplementation of these nutrients may improve wound
      healing. Recent Advances: Oral nutritional supplements and enteral formulas
      providing arginine, glutamine, and micronutrients such as ascorbic acid and zinc
      should improve the healing of pressure ulcers (PU) and the healing of surgical,
      traumatic, and burned wounds. Is their efficacy proved from clinical intervention
      trials? Critical Issues: Formulas that are rich in energy, protein, arginine,
      vitamin C, and zinc can improve PU healing, whereas their efficacy for PU
      prevention is less clear. High-dose supplementation of vitamin C, zinc, and
      pantothenic acid may improve the healing of surgical wounds in healthy subjects.
      Arginine lowers the risk of fistulas in patients undergoing elective surgery due
      to gastrointestinal cancer. However, formulations also enriched with n-3-fatty
      acids and ribonucleic acids lower the risk of several wound complications, thus
      being more effective than isolated arginine. Glutamine and antioxidant
      micronutrients (vitamin C and E, zinc, selenium, and copper) can improve the
      healing of surgical, traumatic, and burned wounds. Future Directions:
      Considerable evidence suggests that formulations, indicated especially for
      critically ill patients, support the healing of PU and the healing of surgical
      and burned wounds. However, their optimal composition with regard to the dose of
      individual components has to be determined in future studies. Further well
      designed trials should investigate the impact of certain nutrients for the
      prevention of PU and for the healing of surgical wounds in healthy subjects.

PMID- 25371853
TI  - Ophthalmic Uses of a Thiol-Modified Hyaluronan-Based Hydrogel.
AB  - Significance: Hyaluronic acid (HA, or hyaluronan) is a ubiquitous naturally
      occurring polysaccharide that plays a role in virtually all tissues in vertebrate
      organisms. HA-based hydrogels have wound-healing properties, support cell
      delivery, and can deliver drugs locally. Recent Advances: A few HA hydrogels can
      be customized for composition, physical form, and biomechanical properties. No
      clinically approved HA hydrogel allows for in vivo crosslinking on
      administration, has a tunable gelation time to meet wound-healing needs, or
      enables drug delivery. Recently, a thiolated carboxymethyl HA (CMHA-S) was
      developed to produce crosslinked hydrogels, sponges, and thin films. CMHA-S can
      be crosslinked with a thiol-reactive crosslinker or by oxidative disulfide bond
      formation to form hydrogels. By controlled crosslinking, the shape and form of
      this material can be manipulated. These hydrogels can be subsequently lyophilized
      to form sponges or air-dried to form thin films. CMHA-S films, liquids, and gels
      have been shown to be effective in vivo for treating various injuries and wounds
      in the eye in veterinary use, and are in clinical development for human use.
      Critical Issues: Better clinical therapies are needed to treat ophthalmic
      injuries. Corneal wounds can be treated using this HA-based crosslinked hydrogel.
      CMHA-S biomaterials can help heal ocular surface defects, can be formed into a
      film to deliver drugs for local ocular drug delivery, and could deliver
      autologous limbal stem cells to treat extreme ocular surface damage associated
      with limbal stem cell deficiencies. Future Directions: This CMHA-S hydrogel
      increases the options that could be available for improved ocular wound care,
      healing, and regenerative medicine.

PMID- 25371854
TI  - Nanofiber Microenvironment Effectively Restores Angiogenic Potential of Diabetic
      Endothelial Cells.
AB  - Objective: The effect of chronic hyperglycemic exposure on endothelial cell (EC)
      phenotype, impaired wound neovascularization, and healing is not completely
      understood. The hypotheses are: 1) chronic exposure to diabetic conditions in
      vivo impairs the angiogenic potential of ECs and 2) this deficiency can be
      improved by an extracellular microenvironment of angiogenic peptide nanofibers.
      Approach: Angiogenic potential of microvascular ECs isolated from diabetic
      (db/db) and wild type (wt) mice was assessed by quantifying migration,
      proliferation, apoptosis, capillary morphogenesis, and vascular endothelial
      growth factor (VEGF) expression for cell cultures on Matrigel (Millipore,
      Billerica, MA) or nanofibers under normoglycemic conditions. The in vivo effects
      of nanofiber treatment on wound vascularization were determined using two mouse
      models of diabetic wound healing. Results: Diabetic ECs showed significant
      impairments in migration, VEGF expression, and capillary morphogenesis. The
      nanofiber microenvironment restored capillary morphogenesis and VEGF expression
      and significantly increased proliferation and decreased cell apoptosis of
      diabetic cells versus wt controls. In diabetic wounds, nanofibers significantly
      enhanced EC infiltration, neovascularization, and VEGF protein levels, as
      compared to saline treatment; this effect was observed even in MMP9 knockout mice
      with endothelial progenitor cell (EPC) deficiency. Innovation: The results
      suggest a novel approach for correcting diabetes-induced endothelial deficiencies
      via cell interactions with a nanofiber-based provisional matrix in the absence of
      external angiogenic stimuli. Conclusion: Impaired endothelial angiogenic
      potential can be restored by angiogenic cell stimulation in the nanofiber
      microenvironment; this suggests that nanofiber technology for diabetic wound
      healing and treatment of other diabetes-induced vascular deficiencies is
      promising.

PMID- 25371855
TI  - Choice of Stimulus Range and Size Can Reduce Test-Retest Variability in
      Glaucomatous Visual Field Defects.
AB  - PURPOSE: To develop guidelines for engineering perimetric stimuli to reduce test
      retest variability in glaucomatous defects. METHODS: Perimetric testing was
      performed on one eye for 62 patients with glaucoma and 41 age-similar controls on
      size III and frequency-doubling perimetry and three custom tests with Gaussian
      blob and Gabor sinusoid stimuli. Stimulus range was controlled by values for
      ceiling (maximum sensitivity) and floor (minimum sensitivity). Bland-Altman
      analysis was used to derive 95% limits of agreement on test and retest, and
      bootstrap analysis was used to test the hypotheses about peak variability.
      RESULTS: Limits of agreement for the three custom stimuli were similar in width
      (0.72 to 0.79 log units) and peak variability (0.22 to 0.29 log units) for a
      stimulus range of 1.7 log units. The width of the limits of agreement for size
      III decreased from 1.78 to 1.37 to 0.99 log units for stimulus ranges of 3.9,
      2.7, and 1.7 log units, respectively (F = 3.23, P < 0.001); peak variability was
      0.99, 0.54, and 0.34 log units, respectively (P < 0.01). For a stimulus range of
      1.3 log units, limits of agreement were narrowest with Gabor and widest with size
      III stimuli, and peak variability was lower (P < 0.01) with Gabor (0.18 log
      units) and frequency-doubling perimetry (0.24 log units) than with size III
      stimuli (0.38 log units). CONCLUSIONS: Test-retest variability in glaucomatous
      visual field defects was substantially reduced by engineering the stimuli.
      TRANSLATIONAL RELEVANCE: The guidelines should allow developers to choose from a
      wide range of stimuli.

PMID- 25371856
TI  - Study of in vitro capillary-like structures in psoriatic skin substitutes.
AB  - Angiogenesis is one of the important hallmarks of psoriasis. The extension of the
      superficial microvascular structure and activated pro-angiogenic mediators in
      psoriasis seem to be important factors involved in the pathology. According to
      the changes of superficial microvasculature in psoriatic lesions, anti-angiogenic
      treatment could be a promising therapeutic strategy for psoriasis. The aim of
      this study was to construct an in vitro vascularized psoriatic skin substitute
      for fundamental research. Psoriatic fibroblasts and keratinocytes were isolated
      from psoriatic plaque biopsies, while healthy fibroblasts and keratinocytes, as
      well as microvascular endothelial cells, were isolated from healthy skin biopsies
      of cosmetic breast surgery. Psoriatic and healthy skin substitutes with and
      without endothelial cells were produced using the self-assembly approach.
      Afterward the substitutes were examined by histology, immunofluorescence studies,
      and three-dimensional (3D) confocal microscopy. Histological analysis and
      immunofluorescence staining of specific markers for endothelial cells (von
      Willebrand, PECAM-1 [CD31], and VE-cadherin [CD144]) and basement membrane
      component (collagen IV) demonstrated that endothelial cells have the ability to
      form capillary-like tubes. Moreover, the 3D branched structure of the capillary
      like structures and an eagle eye view of them were observed by confocal
      microscopy. Also the semiquantification of capillary-like tubes (CLTs) was
      carried out with a 3D eagle eye view of substitutes, and more CLTs were observed
      in psoriatic substitutes. These results suggest that it is possible to observe 3D
      capillary-like structures in the self-assembled psoriatic skin substitutes, which
      could become a good in vitro testing model for anti-angiogenic drug research, and
      facilitate the study of this complex pathology, which links angiogenesis to its
      development. 

PMID- 25371858
TI  - Contribution of fibroblasts to the mechanical stability of in vitro engineered
      dermal-like tissue through extracellular matrix deposition.
AB  - Tissue-engineered skin with mechanical and biological properties that match the
      native tissue could be a valuable graft to treat non-healing chronic wounds.
      Fibroblasts grown on a suitable biodegradable scaffold are a feasible strategy
      for the development of a dermal substitute above which epithelialization may
      occur naturally. Cell growth and phenotype maintenance are crucial to ensure the
      functional status of engineered tissue. In this study, an electrospun
      biodegradable polymer scaffold composed of a terpolymer PLGC [poly(lactide
      glycolide-caprolactone)] with appropriate mechanical strength was used as a
      scaffold so that undesirable contraction of the wound could be prevented when it
      was implanted. To enhance cell growth, synthetic PLGC was incorporated with a
      fibrin-based biomimetic composite. The efficacy of the hybrid scaffold was
      evaluated by comparing it with bare PLGC in terms of fibroblast growth potential,
      extracellular matrix (ECM) deposition, polymer degradation, and mechanical
      strength. A significant increase was observed in fibroblast attachment,
      proliferation, and deposition of ECM proteins such as collagen and elastin in the
      hybrid scaffold. After growing fibroblasts for 20 d and 40 d, immunochemical
      staining of the decellularized scaffolds showed deposition of insoluble collagen
      and elastin on the hybrid scaffold but not on the bare scaffold. The loss of
      mechanical strength consequent to in vitro polymer degradation seemed to be
      balanced owing to the ECM deposition. Thus, tensile strength and elongation were
      better when cells were grown on the hybrid scaffold rather than the bare samples
      immersed in culture medium. Similar patterns of in vivo and in vitro degradation
      were observed during subcutaneous implantation and fibroblast culture,
      respectively. We therefore postulate that a hybrid scaffold comprising PLGC and
      fibrin is a potential candidate for the engineering of dermal tissue to be used
      in the regeneration of chronic wounds. 

PMID- 25371857
TI  - Morphological analysis of human induced pluripotent stem cells during induced
      differentiation and reverse programming.
AB  - The fine analysis of cell components during the generation of pluripotent cells
      and their comparison to bone fide human embryonic stem cells (hESCs) are valuable
      tools to understand their biological behavior. In this report, human mesenchymal
      cells (hMSCs) generated from the human ES cell line H9, were reprogrammed back to
      induced pluripotent state using Oct-4, Sox2, Nanog, and Lin28 transgenes. Human
      induced pluripotent stem cells (hIPSCs) were analyzed using electron microscopy
      and compared with regard to the original hESCs and the hMSCs from which they were
      derived. This analysis shows that hIPSCs and the original hESCs are
      morphologically undistinguishable but differ from the hMSCs with respect to the
      presence of several morphological features of undifferentiated cells at both the
      cytoplasmic (ribosomes, lipid droplets, glycogen, scarce reticulum) and nuclear
      levels (features of nuclear plasticity, presence of euchromatin, reticulated
      nucleoli). We show that hIPSC colonies generated this way presented epithelial
      aspects with specialized junctions highlighting morphological criteria of the
      mesenchymal-epithelial transition in cells engaged in a successful reprogramming
      process. Electron microscopic analysis revealed also specific morphological
      aspects of partially reprogrammed cells. These results highlight the valuable use
      of electron microscopy for a better knowledge of the morphological aspects of
      IPSC and cellular reprogramming. 

PMID- 25371859
TI  - Aged mice repeatedly injected with plasma from young mice: a survival study.
AB  - It was reported using various biological models that the administration of blood
      factors from young animals to old animals could rejuvenate certain functions. To
      assess the anti-aging effect of young blood we tested the influence of repeated
      injections of plasma from young mice on the lifespan of aged mice. One group of
      36 CBA/Ca female mice aged 10-12 months was treated by repeated injections of
      plasma from 2- to 4-month-old females (averaging 75-150 MUL per injection, once
      intravenously and once intraperitoneally per week for 16 months). Their lifespan
      was compared to a control group that received saline injections. The median
      lifespan of mice from the control group was 27 months versus 26.4 months in
      plasma-treated group; the repeated injections of young plasma did not
      significantly impact either median or maximal lifespan. 

PMID- 25371860
TI  - Mathematical Modeling of HIV Dynamics After Antiretroviral Therapy Initiation: A
      Review.
AB  - This review shows the potential ground-breaking impact that mathematical tools
      may have in the analysis and the understanding of the HIV dynamics. In the first
      part, early diagnosis of immunological failure is inferred from the estimation of
      certain parameters of a mathematical model of the HIV infection dynamics. This
      method is supported by clinical research results from an original clinical trial:
      data just after 1 month following therapy initiation are used to carry out the
      model identification. The diagnosis is shown to be consistent with results from
      monitoring of the patients after 6 months. In the second part of this review,
      prospective research results are given for the design of individual anti-HIV
      treatments optimizing the recovery of the immune system and minimizing side
      effects. In this respect, two methods are discussed. The first one combines HIV
      population dynamics with pharmacokinetics and pharmacodynamics models to generate
      drug treatments using impulsive control systems. The second one is based on
      optimal control theory and uses a recently published differential equation to
      model the side effects produced by highly active antiretroviral therapy
      therapies. The main advantage of these revisited methods is that the drug
      treatment is computed directly in amounts of drugs, which is easier to interpret
      by physicians and patients. 

PMID- 25371861
TI  - Effect of long-term osmotic loading culture on matrix synthesis from
      intervertebral disc cells.
AB  - The intervertebral disc is a highly hydrated tissue that acts to absorb and
      distribute large complex loads placed on the spine. Diurnal loading and disc
      degeneration causes significant changes in water volume and proteoglycan content,
      which alters the internal osmotic environment. Short-term osmotic loading alters
      disc cell gene expression; however, the long-term effect of osmotic loading on
      disc cell matrix synthesis is not well understood. The objective of this study
      was to determine the effect of long-term osmotic loading on matrix turnover and
      proliferation by juvenile and adult cells from the nucleus pulposus (NP) and the
      cartilaginous endplate (EP). Matrix synthesis was evaluated using pellets and a
      3D agarose system, which has been used for developing engineered tissues.
      Intervertebral discs were acquired from juvenile and adult cows. Cells were
      acquired through enzymatic digestion and expanded in culture. Pellets were formed
      through centrifugation, and constructs were created by encapsulating cells within
      2% w/v agarose hydrogel. Pellets and constructs were cultured up to 42 days in
      chemically defined medium with the osmolality adjusted to 300, 400, or 500
      mOsm/kg. EP cells were evaluated as a chondrocyte comparison to chondrocyte-like
      NP cells. Pellet and agarose cultures of juvenile NP and EP cells demonstrated
      similarities with respect to cell proliferation and functional mechanical
      properties. Cell proliferation decreased significantly with increased osmotic
      loading. The final compressive Young's modulus of juvenile NP cells was 10-40*
      greater than initial properties (i.e., day 0) and was greater than the final
      Young's modulus of adult NP and juvenile EP constructs. In juvenile NP
      constructs, there were no significant differences in GAG content with respect to
      osmotic loading. However, GAG synthesis and mechanical properties were greatest
      for the 400 mOsm/kg group in adult NP constructs. Taken together, the results
      presented here suggest a tradeoff between cell proliferation and matrix
      production under osmotic loading conditions. In conclusion, culturing disc cells
      in an osmotic environment that best mimics the healthy disc environment (400
      mOsm/kg) may be ideal for balancing cell proliferation, matrix production, and
      mechanical properties of engineered disc tissues. 

PMID- 25371862
TI  - Reusing cadaveric humeri for fracture testing after testing simulated rotator
      cuff tendon repairs.
AB  - The financial cost of using human tissues in biomedical testing and surgical
      reconstruction is predicted to increase at a rate that is disproportionately
      greater than other materials used in biomechanical testing. Our first hypothesis
      is that cadaveric proximal humeri that had undergone monotonic failure testing of
      simulated rotator cuff repairs would not differ in ultimate fracture loads or in
      energy absorbed to fracture when compared to controls (i.e., bones without cuff
      repairs). Our second hypothesis is that there can be substantial cost savings if
      these cadaveric proximal humeri, with simulated cuff repairs, can be re-used for
      fracture testing. Results of fracture tests (conducted in a backwards fall
      configuration) and cost analysis support both hypotheses. Hence, the bones that
      had undergone monotonic failure tests of various rotator cuff repair techniques
      can be re-used in fracture tests because their load-carrying capacity is not
      significantly reduced. 

PMID- 25371863
TI  - Diagnostic value of CD-10 marker in differentiating of papillary thyroid
      carcinoma from benign thyroid lesions.
AB  - BACKGROUND: Using of CD10 in accordance with clinical and histological features
      of thyroid lesions could be used as both diagnostic and prognostic tool, which
      consequently influence the management and their prognosis for survival of
      patients with thyroid neoplasms especially papillary thyroid carcinoma (PTC). The
      aim of this study was to determine its expression in PTC and different benign
      thyroid lesions. MATERIALS AND METHODS: In this descriptive-analytic, cross
      sectional study, paraffin-embedded tissues of patients with definitive pathologic
      diagnosis of different benign thyroid lesions and PTC were retrieved.
      Immunostained sections of each slides was performed using immunohistochemistry
      methods and expression of CD10 was compared in two groups of benign thyroid
      lesions and PTC. RESULTS: From selected cases 134 sections studied in two groups
      of PTC (n = 67) and benign thyroid lesions (n = 67). CD10 were
      immunohistochemically positive in 29.9% of PTC cases, but in none of the thyroid
      benign lesions (0%) (P < 0.001). There was not significant relationship between
      expression of CD10 with age and sex of the studied population (P > 0.05).
      CONCLUSION: The results of the current study indicate that due to the higher
      expression of CD10 in PTC than benign thyroid lesions it might be used for
      differentiating mentioned lesions. But for using it as a diagnostic tool further
      studies with larger sample size and determination of its sensitivity, specificity
      and cut-off point is necessary.

PMID- 25371865
TI  - Analysis of gender based differences in auditory evoked potentials among healthy
      elderly population.
AB  - BACKGROUND: Influence of gender on auditory evoked potentials is contentious.
      Although there are quite a few studies documenting the gender as an influencing
      factor on auditory evoked potentials in younger subjects, but there is a lack of
      similar studies among elderly population. The present study was conducted to find
      out the pattern of gender based differences in auditory evoked potentials among
      healthy elderly subjects. MATERIALS AND METHODS: A cross-sectional study was
      conducted on age matched, healthy males (n = 35) and females (n = 34), aged 50-70
      years. The measures included latencies of waves I-V and interpeak latencies (IPL)
      I-III, III-V and I-V separately for both ears. Data was analyzed statistically
      using Students unpaired t-test, using Statistical Package for Social Sciences
      software v13.0. RESULTS: The values of all the latencies and IPL for both the
      ears were non-significantly higher (P > 0.05) in males as compared to females.
      These results may be attributed to the differences in head circumference between
      both the genders and to the changed hormonal milieu of sex hormones after
      menopause. CONCLUSIONS: Statistical insignificance of latencies among male and
      female elderly subjects excludes gender as an influencing factor on auditory
      evoked potentials in this age group.

PMID- 25371864
TI  - Evaluation of ACE gene I/D polymorphism in Iranian elite athletes.
AB  - BACKGROUND: Angiotensin converting enzyme (ACE) is an important gene, which is
      associated with the successful physical activity. The ACE gene has a major
      polymorphism (I/D) in intron 16 that determines its plasma and tissue levels. In
      this study, we aimed to determine whether there is an association between this
      polymorphism and sports performance in our studied population including elite
      athletes of different sports disciplines. We investigated allele frequency and
      genotype distribution of the ACE gene in 156 Iranian elite athletes compared to
      163 healthy individuals. We also investigated this allele frequency between elite
      athletes in three functional groups of endurance, power, and mixed sports
      performances. MATERIALS AND METHODS: DNA was extracted from peripheral blood, and
      polymerase chain reaction (PCR) method was performed on intron 16 of the ACE
      gene. The ACE genotype was determined for each subject. Statistical analysis was
      performed by SPSS 15, and results were analyzed by Chi-Square test. RESULTS:
      There was a significant difference in genotype distribution and allele frequency
      of the ACE gene in athletes and control group (P = 0.05, P = 0.03, respectively).
      There was also a significant difference in allele frequency of the ACE gene in 3
      groups of athletes with different sports disciplines (P = 0.045). Proportion of
      the ACE gene D allele was greater in elite endurance athletes (37 high-distance
      cyclists) than two other groups. CONCLUSIONS: Findings of the present study
      demonstrated that there is an association between the ACE gene I/D polymorphism
      and sports performance in Iranian elite athletes.

PMID- 25371866
TI  - Formulation, characterization and physicochemical evaluation of amoxicillin
      effervescent tablets.
AB  - BACKGROUND: Amoxicillin is a semisynthetic antibiotic, which is used as an
      antimicrobial drug. This study was designed to formulate amoxicillin effervescent
      tablets, aimed at improved patient compliance and increased drug stability.
      MATERIALS AND METHODS: In this study, nine effervescent tablet formulations were
      prepared from amoxicillin trihydrate. The effervescent base was comprised of
      various amounts of citric acid and sodium bicarbonate. Powders and granules were
      evaluated for their particle size, bulk density, tapped density, compressibility
      index, Hausner's ratio and angle of repose. The effervescent tablets were then
      prepared from powders and granules of acceptable quality by direct compression
      and fusion methods. The tablets were evaluated for weight variation, friability,
      pH of solution, carbon dioxide (CO2) content, hardness, effervescence time,
      thickness, assay, content uniformity, water content and equilibrium moisture
      content. RESULTS: The results indicated better flowability of granules prepared
      by fusion method as compared with the direct compression. The percent weight
      variations of tablets were within the acceptable limit of 0.5%. The friability
      was less than 1% in all formulations. The solution pH of tablets prepared by
      direct compression and fusion methods ranged from 4.55 to 5.74 and 4.74-5.84,
      respectively. The CO2 amounts generated by of fusion method tablets were smaller
      as compared to the direct compression method. The hardness of tablets was 40.66
      56 for direct compression method and 60.6-74.6 for fusion method. The tablets
      produced by the fusion method had a larger thickness and lower water content than
      tablets produced by direct compression method. CONCLUSION: Tablets prepared by
      the fusion method exhibited superior pre- and post-compression characteristics as
      compared to tablets prepared by direct compression method.

PMID- 25371867
TI  - Is there any association of personality traits with vascular endothelial function
      or systemic inflammation?
AB  - BACKGROUND: Evidences showed association of some personality traits with
      increased risk of cardiovascular diseases, but mediated mechanisms are not
      entirely described. In this study, we investigated the association of different
      personality traits with systemic inflammation and endothelial function as
      probable mediators. METHODS: This cross-sectional study was conducted in 2011 on
      40-60 years old employees of an industrial company located in Isfahan city
      (central Iran). Participants were selected through simple random sampling.
      Personality types were evaluated using the neuroticism-extroversion-openness
      personality inventory and systemic inflammatory status was determined with high
      sensitive C-reactive protein (hs-CRP) level. To evaluate endothelial function
      flow mediated dilation (FMD) were measured. The obtained data were analyzed with
      univariate correlation and multiple linear regression tests. RESULTS: A total of
      254 cases with mean age of 51.4 +/- 6.1 years were evaluated. There was no
      significant relationship between hs-CRP level and FMD with the personality traits
      in univariate analysis. In multivariate analysis, no association was found
      between the scores of personality traits and FMD with controlling the factors
      such as age, body mass index dyslipidemia, hypertension and diabetes. Only there
      was an inverse association between conscientiousness score and hs-CRP (beta = 
      0.241, P = 0.013). CONCLUSIONS: In our population who were the employees of an
      industrial company, no relationship was found between specific personality trait
      and endothelial dysfunction. However, we found that the personality trait of
      responsibility (conscientiousness) is negatively associated with inflammation.
      Further multi-center studies and also cohort studies are recommended in this
      regard.

PMID- 25371868
TI  - An observational study on the expression of cyclooxygenase-2 in meningioma.
AB  - BACKGROUND: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in different
      types of tumors and is known to be associated with malignant behavior of tumors.
      We determined the association of COX-2 expression and different grades of human
      meningioma. MATERIALS AND METHODS: This retrospective study was conducted on
      specimens obtained from adult patients with meningioma. Meningioma was classified
      according to the WHO 2007 classification protocol (I, II, and III). COX-2
      expression intensity was scored based on the percentage of immunopositive cells
      as 0: 0-10%; +1: >10% and a part of the cell membrane; +2: >10% and complete cell
      membrane; and +3: >30% and complete cell membrane. Scores of +2 or +3 were
      considered as COX-2 positive. RESULTS: Ninety meningioma cases (mean age = 53.0
      +/- 13.2 years, 71.1% female) were studied. COX-2 was positive in 25% (17/68),
      68.4% (13/19), and 100% (3/3) of cases with tumor grade I, II, and III,
      respectively (P < 0.001). There was a significant correlation between tumor grade
      and COX-2 expression score (Spearman's correlation coefficient = 0.422, P <
      0.001). CONCLUSIONS: There is a strong association between COX-2 expression and
      tumoral grade in meningioma with more aggressive tumors expressing COX-2 with
      more intensity. Prospective studies examining the association of COX-2 expression
      with tumor recurrence and interventional studies examining the role of COX-2
      inhibitors anticancer therapy of meningioma are warranted.

PMID- 25371869
TI  - Intravenous dexamethasone versus ketamine gargle versus intravenous dexamethasone
      combined with ketamine gargle for evaluation of post-operative sore throat and
      hoarseness: A randomized, placebo-controlled, double blind clinical trial.
AB  - BACKGROUND: Sore throat and hoarseness are the most frequent subjective
      complaints after tracheal intubation for general anesthesia. We conducted a
      prospective, randomized, double-blind, placebo controlled study to evaluate the
      efficacy of intravenous (IV) dexamethasone plus ketamine gargle for reducing the
      incidence and severity of post-operative sore throat (POST) and hoarseness.
      MATERIALS AND METHODS: 140 patients (aged 16-65 year) scheduled for elective
      surgery were enrolled. Patients were randomly allocated into four groups of 35
      subjects each: Group K, gargled 40 mg ketamine in 30 ml saline; Group D, were
      infused 0.2 mg/kg IV dexamethasone; Group KD, gargled 40 mg ketamine in 30 ml
      saline plus 0.2 mg/kg IV dexamethasone; Group P (placebo) that received saline
      (gargle and IV). POST was graded at 0, 2, 4, 8, 16 and 24 h after operation on a
      four-point scale (0-3). RESULTS: The incidence and severity of POST were
      significantly lower in Group KD, compared with the other groups at all times
      after tracheal extubation for up to 24 h (P < 0.05). Also the incidence and
      severity of hoarseness were significantly lower in each Groups of KD and K and D
      compared with group placebo (P < 0.05). CONCLUSION: The prophylactic use of 0.2
      mg/kg of IV dexamethasone plus ketamine gargle significantly reduced the
      incidence and severity of POST compared with using each of these drugs alone or
      using placebo.

PMID- 25371870
TI  - The influence of BsmI and TaqI vitamin D receptor gene polymorphisms on the
      intensity of hyperparathyroidism in Iranian hemodialysis patients.
AB  - BACKGROUND: The influence of vitamin D receptor (VDR) gene polymorphisms on the
      regulation of the parathyroid hormone is important in end-stage renal disease
      (ESRD) patients. We analyzed rs1544410 (BsmI) and rs731236 (TaqI) polymorphisms
      of VDR gene in hemodialysis patients to determine their relationship with serum
      intact parathyroid hormone (iPTH). MATERIALS AND METHODS: Ninety hemodialysis
      patients were included in this study. Patients were classified into four groups
      according to their serum iPTH level. Polymorphisms of VDR gene were surveyed
      using polymerase chain reaction-restriction fragment length polymorphism method
      with BsmI and TaqI enzymes in all the patients. RESULTS: Patients age ranged
      between 30 and 60 years (mean +/- SD: 36.0 +/- 11.4) and period undergoing
      hemodialysis 80 +/- 71 months. Patients were divided into four groups based on
      the serum concentration of iPTH. The distribution of VDR gene allelic variation
      for BsmI and TaqI polymorphisms was different between the four groups of uremic
      patients. Analysis of data revealed a significant correlation between the TaqI
      variants and serum iPTH level. There was also a correlation between the BsmI
      variants and serum iPTH level in that patients with the BB genotype were more
      likely to have a higher serum iPTH level. However, the latter was not
      statistically significant. CONCLUSIONS: Genotype of the TaqI and BsmI VDR gene
      polymorphisms is reported in Iranian patients with ESRD. Those with tt or BB
      genotypes may develop more severe secondary hyperparathyroidism.

PMID- 25371871
TI  - The effect of kangaroo mother care on mental health of mothers with low birth
      weight infants.
AB  - BACKGROUND: The mothers of premature infants are at risk of psychological stress
      because of separation from their infants. One of the methods influencing the
      maternal mental health in the postpartum period is kangaroo mother care (KMC).
      This study was conducted to evaluate the effect of KMC of low birth weight
      infants on their maternal mental health. MATERIALS AND METHODS: The study was
      conducted in the Department of Pediatrics of Isfahan University of Medical
      Sciences, Isfahan, Iran. Premature infants were randomly allocated into two
      groups. The control group received standard caring in the incubator. In the
      experimental group, caring with three sessions of 60 min KMC daily for 1 week was
      practiced. Mental health scores of the mothers were evaluated by using the 28
      item General Health Questionnaire. Statistical analysis was performed by the
      analysis of covariance using SPSS. RESULTS: The scores of 50 infant-mother pairs
      were analyzed totally (25 in KMC group and 25 in standard care group). Results of
      covariance analysis showed the positive effects of KMC on the rate of maternal
      mental health scores. There were statistically significant differences between
      the mean scores of the experimental group and control subjects in the posttest
      period (P < 0.001). CONCLUSION: KMC for low birth weight infants is a safe way to
      improve maternal mental health. Therefore, it is suggested as a useful method
      that can be recommended for improving the mental health of mothers.

PMID- 25371872
TI  - Cholestasis progression effects on long-term memory in bile duct ligation rats.
AB  - BACKGROUND: There is evidence that cognitive functions are affected by some liver
      diseases such as cholestasis. Bile duct ligation induces cholestasis as a result
      of impaired liver function and cognition. This research investigates the effect
      of cholestasis progression on memory function in bile duct ligation rats.
      MATERIALS AND METHODS: MALE WISTAR RATS WERE RANDOMLY DIVIDED INTO FIVE GROUPS,
      WHICH INCLUDE: control group for BDL-7, control group for BDL-21, sham group
      (underwent laparotomy without bile duct ligation), BDL-7 group (7 days after bile
      duct ligation), and BDL-21 group (21 days after bile duct ligation). Step-through
      passive avoidance test was employed to examine memory function. In all groups,
      short-term (7 days after foot shock) and long-term memories (21 days after foot
      shock) were assessed. RESULTS: Our results showed that liver function
      significantly decreased with cholestasis progression (P < 0.01). Also our
      findings indicated BDL-21 significantly impaired acquisition time (P < 0.05).
      Memory retrieval impaired 7 (P < 0.05) and 21 days (P < 0.001) after foot shock
      in BDL-7 and BDL-21 groups, respectively. CONCLUSION: Based on these findings,
      liver function altered in cholestasis and memory (short-term and long-term
      memory) impaired with cholestasis progression in bile duct ligation rats. Further
      studies are needed to better insight the nature of progression of brain damage in
      cholestatic disease.

PMID- 25371873
TI  - Comparing the effect of ketamine and benzydamine gargling with placebo on post
      operative sore throat: A randomized controlled trial.
AB  - BACKGROUND: Air way intubation for general anesthesia usually leads to sore
      throat after surgery. Ketamine plays an important role to block a number of
      receptors related to pain. Benzydamine hydrochloride is a non-steroidal anti
      inflammatory drug that has been used to improve oropharyngeal disorders. In this
      study, it was intended to compare the effect of gargling different solutions
      before the surgery on post-operative sore throat (POST) in patients who underwent
      general anesthesia for hysterectomy. MATERIALS AND METHODS: A total of 60
      patients who underwent the elective hysterectomy were entered to the randomized
      controlled trial regarding to the eligibility criteria. Patients were simply
      randomly allocated to three groups and received one code. Every code was
      representative for a specific drug: 20 cc normal saline (control group) or 1.5 mg
      benzydamine in 20 cc solution or 20 mg ketamine in 20 cc solutions. All the
      research teams were blinded to the received solutions. POST was evaluated with
      numerical rating scale. The data were entered to SPSS software and analysis of
      variance (ANOVA) and Kruskal-Wallis one-way analysis of variance test, were
      performed. RESULTS: The mean ages of ketamine, benzydamine, and normal saline
      recipients were not significantly different. The trend of the severity of sore
      throat during the first 24 h after the operation in ketamine recipients was
      significantly lower than the other two groups (P < 0.001). CONCLUSION: The pain
      scale after surgery was reduced by using both ketamine and benzydamine, but the
      ketamine effect was more noticeable.

PMID- 25371874
TI  - Evaluation of the effect of Cyperus rotundus L. in scopolamine-induced learning
      deficit in mice.
AB  - BACKGROUND: Cyperus rotundus L. was used in traditional Iranian medicine to treat
      memory and cognition disorders. The present study was aimed at investigating the
      effect of the extract and essential oil of C. rotundus on memory dysfunction.
      MATERIALS AND METHODS: Cognition was evaluated using the object recognition task
      that was composed of a square wooden open field box with different shape objects.
      The test was consisted of three sections: 15 min exploration, first trial for 12
      min and second one for 5 min. In the second trial the difference in exploration
      between a previously seen object and novel one, was considered as an index of
      memory performance (recognition index). Memory deficit was induced by scopolamine
      (0.5 mg/kg) before injection of plant extracts and essential oil. RESULTS:
      Rivastigmine at 0.6 mg/kg reversed the scopolamine induced memory dysfunction in
      mice (P < 0.05). On the contrary, neither the hydroalcholic extracts (100, 200,
      400 mg/kg) nor the polyphenolic extract (50, 100, 200 mg/kg) and essential oil
      (10, 20, 40 mg/kg) of C. rotundus produced significant improvement of memory
      dysfunction. The fact that rivastigmine reversed the scopolamine-induced memory
      dysfunction confirms the validity of this memory paradigm. CONCLUSION: Using the
      current method of the memory evaluation, none of the tested doses of the plant
      extract or essential oil changed the memory status of the animals, indicating
      either a lack of effective ingredient or unsuitable method for evaluation.

PMID- 25371875
TI  - Assessment of protein tyrosine phosphatases number 22 polymorphism prevalence
      among rheumatoid arthritis patients: A study on Iranian patients.
AB  - BACKGROUND: It has been proposed that Trp (620) allotype of protein tyrosine
      phosphatases number 22 (PTPN22) gene can intensify the susceptibility to
      rheumatoid arthritis (RA) and other autoimmune diseases. Thus, in this study, the
      prevalence of this polymorphism has been surveyed among RA patients compared with
      healthy persons. The samples were selected from Isfahan province (one of the most
      populated area of Iran). MATERIALS AND METHODS: In this study, 100 patients (case
      group) and 100 healthy persons (control group) were participated voluntarily. The
      case group was selected from people who had referred to the rheumatology clinic
      of AlZahra University Hospital to follow-up their treatment and change their
      drugs dosage. The control group members, who were living in Isfahan province,
      mutually had similar age with patients. On a total, 22% of the case group was
      male and 75% of the control group was female. DNA was extracted from the blood
      sample of all cases and controls and the PTPN22 single nucleotide polymorphism
      (SNP) C1858> T gene polymorphism were studied using the polymerase chain reaction
      restriction fragment length polymorphism method. RESULTS: PTPN22 SNP C1858> T
      gene polymorphism was observed in 11 persons (11%) of the case group and 8
      persons (8%) of the control group. CONCLUSION: The results show that the
      difference was not statistically significant in Isfahan RA population (P = 0.47;
      OR = 1.42; 95% CI 0.55-3.69). Although, another study on Iranian population had
      shown that this polymorphism confers susceptibility to RA.

PMID- 25371877
TI  - Effects of menopausal hormone therapy on uterine myoma in menopausal women.
AB  - OBJECTIVES: The aim of the present study is to evaluate the long term effects of
      estrogen-progestogen therapy (EPT) on uterine myomas volume in postmenopausal
      women. METHODS: We performed a retrospective analysis on postmenopausal women
      with asymptomatic uterine myoma during the period between April, 2008 and
      September, 2012. Postmenopause was defined as amenorrhea for longer than a year
      or serum follicle stimulating hormone levels higher than 40 IU/L. The volume of
      the myoma was assessed by transvaginal ultrasonography for every 6 months after
      administration of EPT. RESULTS: Thirty-eight women were included in the study,
      with 32 in the EPT group and 6 in the control group. Overall, uterine myoma
      volume (mean +/- standard deviation, cm(3)) in the EPT group was 19.5 +/- 24.6 at
      baseline, and those at 6 and 12 months were 24.7 +/- 35.1 and 28.5 +/- 56.4,
      respectively. Myoma volume did not change significantly with EPT, and these
      changes were not significantly different from the control group. Myoma volume
      changes were not significantly different in the subgroups according to the route
      of estrogen administrations and the method of progestogen administrations.
      Clinically significant volume increases during one year of EPT was noted in 28.1%
      (9/32), however, only one showed transient increases. CONCLUSION: Our results
      suggest that treating postmenopausal woman with EPT on a long-term basis does not
      increase the volume of uterine myomas.

PMID- 25371876
TI  - The effects of tamoxifen on learning, memory and brain tissues oxidative damage
      in ovariectomized and naive female rats.
AB  - BACKGROUND: Regarding the modulatory effects of tamoxifen (TAM) on the actions of
      estrogen in the present study, the effects of TAM on learning, memory and brain
      tissues oxidative damage in ovariectomized (OVX) and naomicronve female rats was
      investigated. MATERIALS AND METHODS: THE ANIMALS WERE DIVIDED INTO: (1) Sham, (2)
      OVX, (3) Sham-tamoxifen (Sham-TAM) and (4) ovariectomized-tamoxifen (OVX-TAM).
      The animals of the Sham-TAM and OVX-TAM groups were treated by TAM (1 mg/kg; 4
      weeks). RESULTS: In Morris water maze, the escape latency in the OVX group was
      higher than in the Sham group (P < 0.01). The time latency in the animals of OVX
      TAM group was lower than that of OVX group (P < 0.01); however, there were no
      significant differences between the Sham-TAM and Sham groups. In the probe trial,
      the time spent in target quadrant (Q1) by the animals of OVX group was lower than
      that of Sham group (P < 0.01). Interestingly, the animals of OVX-TAM group spent
      more times in target quadrant (Q1) compared with OVX group (P < 0.01). In passive
      avoidance test, the animals of OVX group had lower latencies to enter the dark
      compartment compared with the Sham group (P < 0.05). The time latency to enter
      the dark compartment by animals of OVX-TAM group was higher than in OVX group (P
      < 0.01). In OVX-TAM group, the total thiol concentration was significantly higher
      (P < 0.05) and malondialdehyde concentration was lower (P < 0.01) than OVX group.
      CONCLUSIONS: These results allow us to propose that TAM enhances learning and
      memory of OVX rats. The possible mechanism may be due to the protective effects
      against brain tissues oxidative damage.

PMID- 25371878
TI  - The Relationship between Uterine Myoma Growth and the Endocrine Disruptor in
      Postmenopausal Women.
AB  - OBJECTIVES: To investigate the number of leiomyoma patients-exposed to bisphenol
      A (BPA) and to observe whether the serum concentration of BPA is related to
      leiomyoma growth. METHODS: A total of 158 patients were recruited for this study.
      Leiomyoma patients were divided into three groups, mild (n = 48), moderate (n =
      32) and severe (n = 28), according to the size of leiomyomas. The control (n =
      30) group was defined as having no leiomyomas. Transvaginal ultrasonography was
      used to identify and measure the leiomyomas. Serum BPA concentrations were
      measured by enzyme-linked immunosorbent assay. RESULTS: BPA was detected in 87.0%
      out of a total of 158 samples, and in 86.0% out of 108 leiomyoma patients. In
      detail, the detection rates of serum BPA were 88.0% in the control group, 77.2%
      in the mild group, 90.0% in the moderate group and 96.0% in the severe group. The
      mean BPA concentration in the control group was 0.558 +/- 0.097 ng/mL, the
      leiomyoma groups, the mean BPA concentrations were 0.274 +/- 0.063 ng/mL (mild),
      0.346 +/- 0.064 ng/mL (moderate) and 0.647 +/- 0.039 ng/mL (severe) (P = 0.0003).
      Values represent the mean +/- standard error. CONCLUSION: The detection rates of
      serum BPA in the control and leiomyoma groups were 88.0% and 86.0%, respectively.
      However, there was no significant difference in the serum BPA concentrations
      between the control and leiomyoma groups. To verify the effect of BPA on
      leiomyoma growth, a close and sequential monitoring is recommended for people who
      are at risk for uterine leiomyoma.

PMID- 25371879
TI  - Uterine adenomyosis which developed from hypoplastic uterus in postmenopausal
      woman with mayer-rokitansky-kuster-hauser syndrome: a case report.
AB  - Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) is characterized by vaginal
      agenesis with variable Mullerian duct abnormalities. We report here a case of
      uterine adenomyosis which developed from a hypoplastic uterus in a patient with
      MRKHS. A 55-year-old postmenopausal woman visited a university hospital for
      pelvic mass. She had underwent vaginoplasty via the McIndoe procedure for MRKHS
      at 15 years of age. Pelvic magnetic resonance imaging showed a 5.4 * 4.8 * 4.7 cm
      mass suspicious for a uterine myoma. She received total abdominal hysterectomy
      with bilateral salpingo-oophorectomy, and neither the cervix nor endometrium was
      found grossly in the surgical specimen. The final histologic diagnosis was
      uterine adenomyosis. 

PMID- 25371880
TI  - A case of vaginal cancer with uterine prolapse.
AB  - Primary vaginal cancer combined with uterine prolapse is very rare. We present a
      case of 80-year-old postmenopausal women complaints of something coming out per
      vagina for the past 20 years, along with blood stained discharge, foul odor
      leukorrhea, and severe pelvic pain for the last 3 months. A 4 * 5 cm ulcer was
      present on middle third of vaginal wall with marked edema and ulceration of
      surrounding tissue. The prolapse was reduced under intravenous sedation in
      operating room. On gynecologic examination, uterus was normal in size, no adnexal
      mass was examined, and both parametrium were thickened. Papanicolaou smear was
      normal. Biopsy of the ulcer at vaginal wall revealed invasive squamous cell
      carcinoma of vagina. Magnetic Resonance Imaging of abdomen and pelvis showed left
      hydronephrosis and liver metastasis. Positron emission tomography (PET)/computed
      tomography (CT) revealed metastasis to lung, liver and iliac bone. She died from
      progression of disease one month after diagnosis. 

PMID- 25371881
TI  - A Case of Perimenopausal Endometrial Cancer in a Woman with MSH2 Germline
      Mutation.
AB  - Lynch syndrome is a genetic malignancy syndrome affecting the colon, endometrium,
      and other organs. It is difficult to find a Lynch syndrome patient without any
      family history of cancer. We have recently examined an endometrial cancer patient
      with a MSH2 gene mutation without a family history of cancer. A 55-year old
      Korean woman was admitted to a local clinic for vaginal bleeding. An endometrial
      biopsy revealed the presence of adenocarcinoma (endometrioid type, grade 1).
      After surgical staging, no further adjuvant therapy was required. Analysis of the
      tissue using immunohistochemistry (IHC) showed the endometrium stained negatively
      for MSH2. Microsatellite instability (MSI) was analyzed for five markers. The
      patient was scored as unstable. Further, additional gene sequencing revealed one
      missense mutation in c.23C > T (p.Thr8Met). This is the first case of Lynch
      syndrome endometrial cancer in Korea in which the patient does not have any
      family history of cancer. 

PMID- 25371882
TI  - A case of torsion of a subserosal leiomyoma.
AB  - Uterine leiomyoma is one of the most common gynecological tumor, whereas acute
      torsion of the uterine leiomyoma is very rare. We report a case of subserosal
      leiomyoma that was first detected by ultrasonography, and further confirmed as
      torsion of subserosal leiomyoma by laparoscopic surgery. 

PMID- 25371883
TI  - Endometriosis in a postmenopausal woman on hormonal replacement therapy.
AB  - Endometriosis is a benign disease and an estrogen-dependent disease.
      Postmenopausal endometriosis is rare, because the absence of estrogenic hormone
      production. We report a case of endometriosis presenting in a postmenopausal
      woman with no history of endometriosis before hormone replacement therapy. 

PMID- 25371884
TI  - A case of adenoid Basal carcinoma of the uterine cervix.
AB  - Adenoid basal carcinoma of the uterine cervix is uncommon neoplasia mostly
      occurring in postmenopausal women. It has excellent prognosis and a favorable
      clinical course. In addition, adenoid basal carcinoma is differentiated from
      adenoid cystic carcinoma by histologic and cellular morphologies, and
      immunohistochemistry. In this paper, we present the case of a 22 year old Korean
      female. She initially had a high-grade squamous intraepithelial lesion (HSIL) on
      Pap smear and a subsequent cervical loop electrosurgical excision procedure
      (LEEP) specimen revealing adenoid basal carcinoma. The lesion showed the
      histologic characteristics of adenoid basal carcinoma. Because of the lesion's
      low potential for recurrence and metastasis, the young primipara had a conization
      procedure performed and has been under close observation. 

PMID- 25371886
TI  - Awareness and experience of menopausal symptom and hormone therapy in korean
      postmenopausal women.
AB  - OBJECTIVES: To investigate awareness and experience of menopausal symptom and
      hormone therapy in Korean postmenopausal women. METHODS: A total of 570
      postmenopausal women were accepted our survey. The women filled out the
      questionnaires composed of medical and surgical history, menopausal age and
      symptom, demand of treatment on menopausal symptom, and personal method for
      overcoming the symptom. Also, we make inquiries about experience of hormone
      therapy, concern about hormone therapy, improvement of menopausal symptom after
      therapy, adverse effect, and cause of cease the therapy. RESULTS: According to
      the survey, 80% (456/570) of the women experienced menopausal symptom. When they
      felt the symptom at first, 47% (213/570) of women was 46-50 years old. The most
      common menopausal symptom was hot flushes (141/570). A number of Korean women
      regarded that menopause was a natural process of ageing (69%). Eighty two % of
      women thought to need to have treatment on menopausal symptom. However, only half
      (43%) visited doctor. The most concerned disease after menopause they had
      answered was osteoporosis (60%) but only 22% of women were taken regular check-up
      of bone mineral density. The common causes were unwilling to do treatment were
      concern about adverse effect (51%) and indefinite fear of cancer (32%). Moreover,
      many women got diverse information about menopause from the mass media than
      professional advice. CONCLUSION: Only a minority of Korean postmenopausal women
      with menopausal symptoms had taken a hormone therapy. We should provide
      appropriate education and counsel to Korean peri-menopause women.

PMID- 25371885
TI  - Postmenopausal hypertension and sodium sensitivity.
AB  - It has been well established that women generally have lower incidence rates of
      hypertension than men at similar ages and these differences may vary with age. It
      also has been observed in many studies that after menopause, blood pressure (BP)
      increases in women to levels even higher than in men. The lack of estrogens may
      not be suggested as the only component involved in the development of
      postmenopausal hypertension. Thus, in this mini-review, the possible mechanisms
      by which sex hormones may influence the BP are discussed. This review also
      examines the renal regulatory mechanisms for gender differences in BP and
      explores the effects of salt intake on BP (salt-sensitivity) in pre and post
      menopausal women. Estrogen has been shown to stimulate nitric oxide (NO)
      production, thus female sex hormones have a beneficial effect on BP control.
      Evidences that angiotensin type 2 receptor (AT2R) is up-regulated by estrogen
      support the favorable effects on BPs in women than men. The kidney plays an
      integral role in the regulation of arterial pressure through the mechanism of
      pressure-natriuresis, which has been shown to be modulated by the RAS. The
      prevalence of salt-sensitivity increases with age and low-salt diets has shown to
      help reduce systolic BP (SBP) and diastolic BP. While oral hormone replacement
      therapy has yielded only a neutral or minimal effect on the elevation of SBP,
      both the transdermal route replacement and a novel progestin with anti
      aldosterone activity (drospirenone) has also shown to reduce SBP. 

PMID- 25371887
TI  - Hereditary risk evaluation for borderline ovarian tumors based on
      immunohistochemistry.
AB  - OBJECTIVES: Borderline ovarian tumors (BOT) are premalignant lesions.
      Approximately 10% of all epithelial ovarian cancers are known to be hereditary
      with hereditary breast and ovarian cancer (HBOC) accounting for approximately 90%
      of cases; the remaining 10% are attributable to Lynch syndrome, also known as
      hereditary nonpolyposis colorectal cancer (HNPCC). The aim of our study is to
      estimate this risk based on screening immunohistochemistry (IHC). METHODS: Thirty
      four patients diagnosed with BOT were identified. Family history, clinical
      characteristics, and IHC data (breast cancer 1, early onset [BRCA1], breast
      cancer 2, early onset [BRCA2], mutS homolog 2 [MSH2], mutL homolog 1 [MLH1]) were
      collected for all cases from the patients' medical charts. Nuclear staining of
      the tumor was scored as negative and positive. RESULTS: Among 32 patients, 14
      (44%) had serous type and 18 (56%) had mucinous type. The mean patient age was 44
      years (range 19-86).The number of patients with weak IHC staining for MSH2 and
      BRCA2 was 1 (3%) and 6 (19%) respectively. The median follow up was 21.8 months.
      CONCLUSION: According to the results, we discovered that 3% and 19% of patients
      with BOT had a risk of hereditary cancer based on IHC analysis respectively. This
      pilot study may help clinician to counsel effectively for confirmative tests.

PMID- 25371888
TI  - Mitochondrial Channel Opener Diazoxide Attenuates Hypoxia-Induced sFlt-1 Release
      in Human Choriocarcinoma Cells.
AB  - OBJECTIVES: To examine the effect of diazoxide on hypoxia-induced soluble fms
      like tyrosin kinase-1 (sFlt-1) release in JEG-3 choriocarcinoma cells. METHODS:
      Cells were cultured under normoxia (20% O2) or hypoxia (1% O2), and expression of
      sFlt-1 mRNA and protein release was determined by quantitative real-time reverse
      transcriptase polymerase chain reaction (qRT-PCR) assays and enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Tumor necrosis factor-alpha (TNF-alpha) as
      well as hypoxia stimulated sFlt-1 release and diazoxide inhibited both of them.
      The selective inhibitor of mitochondrial adenosine triphosphat (ATP)-sensitive
      K(+) channel opener (KATP) 5-hydroxydecanoate (5-HD) completely reversed the
      diazoxide-induced inhibition of hypoxia-stimulated sFlt-1 release. qRT-PCR and
      Western blot analyses showed that diazoxide up-regulated the heme oxygenase-1 (HO
      1) expression. In addition, the HO-1 inducer cobalt protoporphyrin (CoPP) and the
      metabolic product of HO-1 bilirubin mimicked diazoxide to inhibit sFlt-1 release
      and reactive oxygen species (ROS) production under hypoxia, whereas the HO-1
      inhibitor zinc protoporphyrin IX (ZnPP IX) antagonized the effect of diazoxide.
      In cells transfected with the HO-1 siRNA, diazoxide did not exert any effect on
      sFlt-1 release and ROS production under hypoxia. CONCLUSION: These results, taken
      together, strongly suggest that up-regulation of the HO-1 expression is the
      crucial mechanism responsible for the diazoxide-induced inhibition of the sFlt-1
      release and ROS production under hypoxia.

PMID- 25371889
TI  - Endosalpingiosis in postmenopausal elderly women.
AB  - In gynecology, endosalpingiosis is a benign condition in which the fallopian tube
      like epithelium is found outside the fallopian tube. The thirty-four point five
      percent of endosalpingiosis cases have concurrent endometriosis and 40% of the
      endosalpingiosis group are in postmenopausal states. In contrast with
      endometriosis, there are no significant links between infertility, chronic pelvic
      pain and endosalpingiosis. The symptoms of endosalpingiosis are not yet settled.
      Endosalpingiosis is almost always an incidental finding; it is commonly found
      through microscopic examinations, and is then confirmed by pathologists for
      excision and biopsy. Therefore, the clinical differential diagnosis of an
      intramural mass is more important for clinicians when discussing further surgery
      with the patients. We report case of woman who has endosalpingiosis and is
      presented with vaginal bleeding. We first suspect the disease during physical
      examination. Under the impression of pelvic mass, laboratory tests and
      radiological images of contrast enhanced chest computer tomography are taken.
      Images show multisepted cystic masses in left adnexa. To rule out the pelvic
      mass, we executed exploratory laparotomy. Pathologic results show
      endosalpingiosis near the ovary section. But the endosalpingiosis, is not
      generally considered a pathology, and thus, no treatment is necessary. 

PMID- 25371890
TI  - Abdominal wall metastasis of uterine papillary serous carcinoma in a post
      menopausal woman: a case report.
AB  - Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial
      cancer characterized by a high recurrence rate and poor prognosis. We report a
      case of a 58-year-old post-menopausal woman with an abdominal wall metastasis in
      stage IA UPSC. After surgical staging, she did not receive additional adjuvant
      therapy. An egg sized palpable mass developed in the right lower abdomen after 8
      months. Both Abdominopelvic computed tomography (CT) and positron emission
      tomography (PET)-CT revealed a metastatic lesion in the abdominal wall. Hence,
      surgical excision was performed. The pathological findings showed metastatic UPSC
      with clear resection margin. After the diagnosis of UPSC metastasis in the
      abdominal wall, she received chemotherapy utilizing paclitaxel and carboplatin.
      After 3 years, no evidence of recurrence was found. Therefore, we suggest that
      even when UPSC is confined to the endometrium without lymph node metastasis and
      without lymphovascular invasion, chemotherapy should be considered as a
      postoperative adjuvant therapy. 

PMID- 25371891
TI  - A case of ovarian steroid cell tumor, not otherwise specified, treated with
      surgery and gonadotropin releasing hormone agonist.
AB  - Steroid cell tumors account for less than 0.1% of all ovarian tumors. There are
      three steroid cell tumor subtypes: steroid cell tumor not otherwise specified
      (NOS), stromal luteoma and Leydig cell tumor. Steroid cell tumor, NOS, is the
      most common type and has malignant potential. This report describes a case of an
      ovarian steroid cell tumor, NOS. A 35-year-old woman visited hospital with the
      complaint of metrorrhagia. Physical examination revealed increased pubic hair.
      Transvaginal ultrasound indentified a 4.9 * 3.4 cm, well-circumscribed and solid
      left ovarian tumor. After laparoscopic left oophorectomy, the tumor was revealed
      as an ovarian steroid cell tumor, NOS. During the laparoscopic surgery, tumor
      ruptured. Complete surgical staging was performed and no evidence of metastasis
      was found. Gonadotropin releasing hormone agonist was administered monthly for 6
      months. The patient has had no evidence of recurrence for 43 months. 

PMID- 25371892
TI  - Perimenopausal ovarian carcinoma patient with subclavian node metastasis proven
      by immunohistochemistry.
AB  - Ovarian cancer is the seventh most common cancer in the world and the fifth most
      common cause of death from cancer; it is responsible for over half of all deaths
      related to gynecological cancers. The presence of lymphatic metastasis is an
      important prognostic factor in ovarian cancer. Nodal metastases to the pelvic and
      the para-aortic lymph nodes are common, particularly in an advanced of the
      disease (stages III-IV). The finding of distant nodal metastasis, especially
      subclavian lymph node metastasis, from ovarian carcinoma is very uncommon. 18F
      fluorodeoxyglucose-positron emission tomography (FDG-PET) or FDG-PET/computed
      tomography (CT) provides an improved imaging for detecting metastatic lymph nodes
      in patients with ovarian cancer. Immunohistochemically, ovarian carcinoma cells
      are positive for estrogen receptor, progesterone receptor, cancer antigen 125,
      Wilms' tumor 1 protein, and p53; they are negative for thyroid transcription
      factor (TTF-1) and caudal-related homeobox 2 (CDX-2). This report describes a
      Korean woman diagnosed with ovarian cancer with subclavian lymph node metastasis
      revealed by FDG PET/CT and verified by an immunohistochemical staining.
      Differentiating between the primary ovarian lesion and the metastatic lesion will
      allow the initiation of an appropriate treatment and help predict the prognosis. 

PMID- 25371893
TI  - Gaps in menopause knowledge.
AB  - The average middle aged woman goes through a volatile period of endocrine
      fluctuations as she passes through menopause and the stages that precede and
      follow it. Ovarian hormones are steroid hormones. They readily cross the cell and
      nuclear membranes and influence transcription of numerous genes. Such influences
      are tissue specific and state specific. In short, changes in ovarian hormones
      mean that a women will experience changes in her entire body systems. When an
      individual woman's constitutional factors, pathologic states, medications,
      environmental exposures are taken into consideration, the integrated changes
      become too complex to predict. Inter-study sampling differences with the
      complexities in the backdrop may have led to conflicting conclusions in menopause
      research. This paper reviews some of the controversies in the care of menopausal
      women. 

PMID- 25371894
TI  - Comparison of Buckling Ratio and Finite Element Analysis of Femoral Necks in Post
      menopausal Women.
AB  - OBJECTIVES: Osteoporosis is a prevalent problem amongst the elderly. Bone mineral
      density (BMD) obtained from dual X-ray absorptiometry (DXA) is the gold standard
      in diagnosing osteopenia (-1.0 < t < -2.5) and osteoporosis (t > -2.5). However,
      following osteoporosis therapy, increases in BMD may be unreliable. Although hip
      fracture risk can be reduced with the aid of drugs, treated patients still face
      considerable risk as most people who sustain hip fracture do not have generalized
      osteoporosis. A study of the local distribution of bone mass was necessary as
      they contribute to the geometry and consequently the bone strength. METHODS: By
      identifying the respective regions in the femoral neck, the geometric changes
      were localized and differed between each patient, proving that drug treatment
      elicits local changes in mean outer radius and mean cortical thickness. Numerical
      analysis also validated the above findings, where critical strain regions were
      predicted at similar zones and this is coherent with the fact that reduced
      thickness of the cortical bone has been related to increased risk of fracture
      initiation. RESULTS: Hence, from individual radar plots, we can determine if the
      effect of drugs had outweighed the effect of aging. We can then propose a course
      of treatment drug better suited for the patient in the clinical scenario.
      CONCLUSION: Clinically, little conclusion can be drawn from just the BMD in
      osteopenic / osteoporotic patients. This emphasizes the necessity of using
      geometry and structure to predict fracture risk. Focusing on a patient specific
      analysis at a local level will improve diagnosis of osteoporosis and ultimately
      fracture prediction.

PMID- 25371896
TI  - Premenstrual syndrome and premenstrual dysphoric disorder in perimenopausal
      women.
AB  - OBJECTIVES: To evaluate the prevalence of premenstrual syndrome (PMS) and
      premenstrual dysphoric disorder (PMDD) of perimenopausal women at a university
      hospital along with their menstrual characters. METHODS: A questionnaire survey
      regarding premenstrual symptoms was carried out in 100 perimenopausal women (43
      to 53, years). The pattern of menstruation and, the intensity of dysmenorrhea
      were assessed; and further, the symptoms were classified according to their
      number, intensity, and persistence. The PMS criteria of American College of
      Obstetrics and Gynecology (ACOG) and PMDD criteria by American Psychiatric
      Association (APA) were evaluated. RESULTS: The approximate prevalence of PMS
      criteria was 95% and that of PMDD criteria was 23%. The most dominant symptoms
      were 'breast tenderness', 'abdominal bloating', 'and headache'. PMDD was
      significantly associated with the severity of dysmenorrhea (P = 0.020). There was
      no significant relation with age, height, weight, body mass index and the cycle
      of menstruation. CONCLUSION: Most women experience PMS and PMDD, which and have a
      significant impact on the activity of perimenopause women. However in most women
      that do not know well about PMS and PMDD. We should educate and inform women of
      PMS and PMDD, thus helping them increase their quality of life.

PMID- 25371895
TI  - Sildenafil Inhibits Advanced Glycation End Products-induced sFlt-1 Release
      Through Upregulation of Heme Oxygenase-1.
AB  - OBJECTIVES: We examined the effect of sildenafil citrate on advanced glycation
      end products (AGEs)-induced soluble fms-like tyrosine kinase 1 (sFlt-1) release
      in JEG-3 choriocarcinoma cells. METHODS: Cells were incubated with control bovine
      serum albumin (BSA) or AGEs-BSA, and expression of sFlt-1 mRNA and protein
      release was determined by quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively.
      AGEs-BSA increased sFlt-1 mRNA expression and protein release in a dose-dependent
      manner. RESULTS: Sildenafil citrate suppressed sFlt-1 mRNA expression and protein
      release in cells treated with AGEs-BSA in a dose-dependent manner. Likewise, it
      inhibited the increase of reactive oxygen species (ROS) production and NF-kappaB
      activity in these cells. Cobalt protoporphyrin (CoPP) and bilirubin also
      inhibited sFlt-1 release and ROS production in cells treated with AGEs-BSA,
      whereas zinc protoporphyrin IX (ZnPP IX) antagonized the effect of sildenafil
      citrate. In cells transfected with the heme oxygenase-1 (HO-1) siRNA, sildenafil
      citrate failed to inhibit the sFlt-1 release and ROS production. CONCLUSION:
      These results strongly suggest that sildenafil citrate inhibits sFlt-1 release
      and ROS production in cells treated with AGEs-BSA through upregulation of the HO
      1 expression in JEG-3 cells.

PMID- 25371897
TI  - Comparison of Laparoscopic Radiofrequency Myolysis (LRFM) and Ultrasonographic
      Radiofrequency Myolysis (URFM) in Treatment of Midline Dysmenorrhea.
AB  - OBJECTIVES: To access the effectiveness of radiofrequency myolysis (RFM) in women
      with midline dysmenorrhea. METHODS: We designed RFM in two ways laparoscopic RFM
      (LRFM), vaginal ultrasound-guided RFM (URFM). One hundred and thirty-two patients
      were in the LRFM group and, 140 patients were in the URFM group. RESULTS: Upon
      receipt of surgery, both the LRFM and the URFM groups demonstrated a significant
      decrease (P < 0.001) in the mean pain score when compared to those before and
      after surgery. CONCLUSION: The RF uterine myolysis procedure provides an
      alternative for those patients who suffer from intractable midline dysmenorrhea.
      LRFM is an alternative choice because it is relatively safe and, simple to
      perform and moreover, it is satisfactory. LRFM appears to increasingly succeed in
      the treatment of midline dysmenorrhea.

PMID- 25371898
TI  - Sclerosing stromal tumor in an elderly postmenopausal woman.
AB  - Sclerosing stromal tumor (SST) of the ovary is a rare tumor derived from the sex
      cord stroma. This tumor was first described by Chalvaridjian and Scully in 1973.
      SST of the ovary is prevalence of 1.5% to 6% of ovarian stromal tumors. Patients
      are most commonly diagnosed in their 20s and 30s. There have been reports of SST
      postmenopausal women aged 65-, 67-, and 71 in the Republic of Korea; however, no
      report of this disease has been reported in women older than 80. In this study,
      we would like to report an 80-year-old postmenopausal woman who did not
      previously complain of any symptoms, and was finally diagnosed with SST. She was
      involved in a traffic accident, and huge pelvic mass was found during the
      evaluation of intra-abdominal hemorrhage. Total abdominal hysterectomy with
      bilateral salpingo-oophorectomy was performed ; a final pathologic diagnosis
      reported SST. 

PMID- 25371899
TI  - Sense of coherence and personality traits related to depressive state.
AB  - Aims. The current study aims to examine the influence of job stress, SOC, and
      personality traits on depressive state. Methods. A self-reported survey was
      conducted among 347 female nurses in a general hospital. Job stress was measured
      using the Japanese version of the Brief-Job Stress Questionnaire scale.
      Depressive state was assessed by the K6 scale. We used 13-item SOC scale.
      Personality traits were assessed by the Japanese version of Ten-Item Personality
      Inventory. Multiple liner regression analyses were conducted to examine
      predictors that significantly affect depressive state. Results. Job and life
      satisfaction and SOC negatively related to the depressive state (beta = -0.76, P
      < 0.01; beta = -0.18, P < 0.001, resp.) while neuroticism was positively
      correlated (beta = 0.49, P < 0.001). Also, intrinsic rewards tended to negatively
      relate (beta = -0.80, P < 0.1). Conclusions. From a practical perspective, the
      possible influence of SOC and neurotic personality on depressive state should be
      considered for health care professionals. 

PMID- 25371900
TI  - Freeze-drying of plant tissue containing HBV surface antigen for the oral vaccine
      against hepatitis B.
AB  - The aim of this study was to develop a freeze-drying protocol facilitating
      successful processing of plant material containing the small surface antigen of
      hepatitis B virus (S-HBsAg) while preserving its VLP structure and
      immunogenicity. Freeze-drying of the antigen in lettuce leaf tissue, without any
      isolation or purification step, was investigated. Each process step was
      consecutively evaluated and the best parameters were applied. Several drying
      profiles and excipients were tested. The profile of 20 degrees C for 20 h for
      primary and 22 degrees C for 2 h for secondary drying as well as sucrose
      expressed efficient stabilisation of S-HBsAg during freeze-drying. Freezing rate
      and postprocess residual moisture were also analysed as important factors
      affecting S-HBsAg preservation. The process was reproducible and provided a
      product with VLP content up to 200 ug/g DW. Assays for VLPs and total antigen
      together with animal immunisation trials confirmed preservation of antigenicity
      and immunogenicity of S-HBsAg in freeze-dried powder. Long-term stability tests
      revealed that the stored freeze-dried product was stable at 4 degrees C for one
      year, but degraded at elevated temperatures. As a result, a basis for an
      efficient freeze-drying process has been established and a suitable semiproduct
      for oral plant-derived vaccine against HBV was obtained. 

PMID- 25371901
TI  - Prognostic implication of predominant histologic subtypes of lymph node
      metastases in surgically resected lung adenocarcinoma.
AB  - The International Association for the Study of Lung Cancer, American Thoracic
      Society, and European Respiratory Society (IASLC/ATS/ERS) proposed a new
      classification for lung adenocarcinoma (AD) based on predominant histologic
      subtypes, such as lepidic, papillary, acinar, solid, and micropapillary; this
      system reportedly reflects well outcomes of patients with surgically resected
      lung AD. However, the prognostic implication of predominant histologic subtypes
      in lymph nodes metastases is unclear so far. In this study, we compared
      predominant subtypes between primary lung tumors and lymph node metastatic
      lesions in 24 patients with surgically treated lung adenocarcinoma with lymph
      node metastases. Additionally, we analyzed prognostic implications of these
      predominant histologic subtypes. We observed several discordance patterns between
      predominant subtypes in primary lung tumors and lymph node metastases.
      Concordance rates were 22%, 64%, and 100%, respectively, in papillary-, acinar-,
      and solid-predominant primary lung tumors. We observed that the predominant
      subtype in the primary lung tumor (HR 12.7, P = 0.037), but not that in lymph
      node metastases (HR 0.18, P = 0.13), determines outcomes in patients with
      surgically resected lung AD with lymph node metastases. 

PMID- 25371902
TI  - A derived network-based interferon-related signature of human macrophages
      responding to Mycobacterium tuberculosis.
AB  - Network analysis of transcriptional signature typically relies on direct
      interaction between two highly expressed genes. However, this approach misses
      indirect and biological relevant interactions through a third factor (hub). Here
      we determine whether a hub-based network analysis can select an improved
      signature subset that correlates with a biological change in a stronger manner
      than the original signature. We have previously reported an interferon-related
      transcriptional signature (THP1r2Mtb-induced) from Mycobacterium tuberculosis (M.
      tb)-infected THP-1 human macrophage. We selected hub-connected THP1r2Mtb-induced
      genes into the refined network signature TMtb-iNet and grouped the excluded genes
      into the excluded signature TMtb-iEx. TMtb-iNet retained the enrichment of
      binding sites of interferon-related transcription factors and contained
      relatively more interferon-related interacting genes when compared to THP1r2Mtb
      induced signature. TMtb-iNet correlated as strongly as THP1r2Mtb-induced
      signature on a public transcriptional dataset of patients with pulmonary
      tuberculosis (PTB). TMtb-iNet correlated more strongly in CD4(+) and CD8(+) T
      cells from PTB patients than THP1r2Mtb-induced signature and TMtb-iEx. When TMtb
      iNet was applied to data during clinical therapy of tuberculosis, it resulted in
      the most pronounced response and the weakest correlation. Correlation on dataset
      from patients with AIDS or malaria was stronger for TMtb-iNet, indicating an
      involvement of TMtb-iNet in these chronic human infections. Collectively, the
      significance of this work is twofold: (1) we disseminate a hub-based approach in
      generating a biologically meaningful and clinically useful signature; (2) using
      this approach we introduce a new network-based signature and demonstrate its
      promising applications in understanding host responses to infections. 

PMID- 25371903
TI  - High resolution melting analysis for rapid mutation screening in gyrase and
      Topoisomerase IV genes in quinolone-resistant Salmonella enterica.
AB  - The increased Salmonella resistance to quinolones and fluoroquinolones is a
      public health concern in the Southeast Asian region. The objective of this study
      is to develop a high resolution melt curve (HRM) assay to rapidly screen for
      mutations in quinolone-resistant determining region (QRDR) of gyrase and
      topoisomerase IV genes. DNA sequencing was performed on 62 Salmonella strains to
      identify mutations in the QRDR of gyrA, gyrB, parC, and parE genes. Mutations
      were detected in QRDR of gyrA (n = 52; S83F, S83Y, S83I, D87G, D87Y, and D87N)
      and parE (n = 1; M438I). Salmonella strains with mutations within QRDR of gyrA
      are generally more resistant to nalidixic acid (MIC 16 > 256 MUg/mL). Mutations
      were uncommon within the QRDR of gyrB, parC, and parE genes. In the HRM assay,
      mutants can be distinguished from the wild-type strains based on the transition
      of melt curves, which is more prominent when the profiles are displayed in
      difference plot. In conclusion, HRM analysis allows for rapid screening for
      mutations at the QRDRs of gyrase and topoisomerase IV genes in Salmonella. This
      assay markedly reduced the sequencing effort involved in mutational studies of
      quinolone-resistance genes. 

PMID- 25371904
TI  - Ovarian cancer screening practices of obstetricians and gynecologists in puerto
      rico.
AB  - BACKGROUND: Ovarian cancer is the most fatal malignancy of the female genital
      tract and is associated with high mortality. The American Congress of
      Obstetricians and Gynecologists (ACOG) and the United States Preventive Services
      Task Force (USPSTF) recommend against screening for ovarian cancer in
      asymptomatic, average-risk women. OBJECTIVE: To assess the ovarian cancer
      screening practices in asymptomatic, average-risk women among obstetricians and
      gynecologists (Ob/Gyn) in Puerto Rico. Methodology. From 2011 to 2012, self
      administered anonymous questionnaires were mailed to all licensed obstetricians
      and gynecologists in PR. RESULTS: Response rate was 25%. Overall, 53.9% were
      screening for the disease. Reported screening methods were CA-125 and
      transvaginal ultrasound (TVUS), 39.2%, TVUS only, 30.4%, and CA-125 only, 9.8%.
      In the logistic regression model, the odds that a given health practitioner
      routinely screened for ovarian cancer in the asymptomatic, average-risk
      population increased by 8% with every unit increase in his or her years in
      practice. CONCLUSION: The majority of the practicing Ob/Gyn in PR who
      participated are not following the guidelines established by the ACOG and the
      USPSTF for ovarian cancer screening.

PMID- 25371906
TI  - Characterization of diabetic neuropathy in the Zucker diabetic Sprague-Dawley
      rat: a new animal model for type 2 diabetes.
AB  - Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley
      (ZDSD/Pco) was created. In this study we sought to characterize the development
      of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a
      control. Rats were examined at 34 weeks of age 12 weeks after the onset of
      hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin
      resistant with slowing of both motor and sensory nerve conduction velocities.
      ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides,
      and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of
      ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and
      sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the
      skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the
      number of Langerhans cells was decreased. Vascular reactivity of epineurial
      arterioles, blood vessels that provide circulation to the sciatic nerve, to
      acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats.
      These data indicate that ZDSD rats develop many of the neural complications
      associated with type 2 diabetes and are a good animal model for preclinical
      investigations of drug development for diabetic neuropathy. 

PMID- 25371907
TI  - Vitamin D status and its relationship with metabolic markers in persons with
      obesity and type 2 diabetes in the UAE: a cross-sectional study.
AB  - AIM: To report vitamin D status and its impact on metabolic parameters in people
      in the United Arab Emirates with obesity and type 2 diabetes (T2D). METHODOLOGY:
      This cross-sectional study included 309 individuals with obesity and T2D who were
      randomly selected based on study criteria. Serum concentrations of 25-hydroxy
      vitamin D (s-25(OH)D), calcium, phosphorus, parathyroid hormone, alkaline
      phosphatase, glycemic profile, and cardiometabolic parameters were assessed in
      fasting blood samples, and anthropometric measurements were recorded. RESULTS:
      Vitamin D deficiency (s-25(OH)D < 50 nmol/L) was observed in 83.2% of the
      participants, with a mean s-25(OH)D of 33.8 +/- 20.3 nmol/L. Serum 25(OH)D
      correlated negatively (P < 0.01) with body mass index, fat mass, waist
      circumference, parathyroid hormone, alkaline phosphatase, triglycerides, LDL
      cholesterol, and apolipoprotein B and positively (P < 0.01) with age and calcium
      concentration. Waist circumference was the main predictor of s-25(OH)D status.
      There was no significant association between serum 25(OH)D and glycemic profile.
      CONCLUSION: There is an overwhelming prevalence of vitamin D deficiency in our
      sample of the Emirati population with obesity and T2D. Association of s-25(OH)D
      with body mass index, waist circumference, fat mass, markers of calcium
      homeostasis and cardiometabolic parameters suggests a role of vitamin D in the
      development of cardiometabolic disease-related process.

PMID- 25371905
TI  - Role of endothelial nitric oxide synthase in diabetic nephropathy: lessons from
      diabetic eNOS knockout mice.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in many
      countries. The animal models that recapitulate human DN undoubtedly facilitate
      our understanding of this disease and promote the development of new diagnostic
      markers and therapeutic interventions. Based on the clinical evidence showing the
      association of eNOS dysfunction with advanced DN, we and others have created
      diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic
      mice exhibit advanced nephropathic changes with distinct features of progressive
      DN, including pronounced albuminuria, nodular glomerulosclerosis, mesangiolysis,
      and arteriolar hyalinosis. These studies clearly defined a critical role of eNOS
      in DN and developed a robust animal model of this disease, which enables us to
      study the pathogenic mechanisms of progressive DN. Further, recent studies with
      this animal model have explored the novel mechanisms by which eNOS deficiency
      causes advanced DN and provided many new insights into the pathogenesis of DN.
      Therefore, here we summarize the findings obtained with this animal model and
      discuss the roles of eNOS in DN, unresolved issues, and future investigations of
      this animal model study. 

PMID- 25371908
TI  - Effects of awakening and the use of topical dexamethasone and levofloxacin on the
      cytokine levels in tears following corneal transplantation.
AB  - OBJECTIVES: To study the short-term effect of eye opening and use of topical
      dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in
      human tears. METHODS: Prospective experimental design was used for tear
      collection from eyes of 10 healthy controls and 20 patients four days after
      penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or
      levofloxacin. The concentrations of different cytokines were measured by
      cytometric bead array. RESULTS: At eye opening, IL-6 levels were higher in the
      PKP group as compared to the controls. Thirty minutes later, the released levels
      of IL-10, IL-13, IL-17, IFNgamma, and CCL5 increased in controls, while CXCL8
      decreased in both control and PKP groups. The release of the cytokines remained
      stable after 30 mins except for IFNgamma, which showed a decrease in the controls
      following levofloxacin instillation. No short-term effects of the topically used
      dexamethasone and levofloxacin could be detected on the cytokine levels in
      controls and after PKP. CONCLUSIONS: Evidence of changes in the levels and time
      course of tear cytokines after awakening or eye opening could be established and
      the short-term confounding effects of dexamethasone and levofloxacin on the
      levels of released cytokines in human tears could be excluded.

PMID- 25371909
TI  - Alpha/beta T-cell depleted grafts as an immunological booster to treat graft
      failure after hematopoietic stem cell transplantation with HLA-matched related
      and unrelated donors.
AB  - Allogeneic hematopoietic stem cell transplantation is associated with several
      complications and risk factors, for example, graft versus host disease (GVHD),
      viral infections, relapse, and graft rejection. While high levels of CD3+ cells
      in grafts can contribute to GVHD, they also promote the graft versus leukemia
      (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor
      can be used as a treatment after transplantation for relapse or poor immune
      reconstitution but also they increase the risk for GVHD. In peripheral blood, 95%
      of T-cells express the alphabeta T-cell receptor and the remaining T-cells
      express the gammadelta T-cell receptor. As alphabeta T-cells are the primary
      mediators of GVHD, depleting them from the graft should reduce this risk. In this
      pilot study, five patients transplanted with HLA-matched related and unrelated
      donors were treated with alphabeta T-cell depleted stem cell boosts. The majority
      of gammadelta T-cells in the grafts expressed Vdelta2 and/or Vgamma9. Most
      patients receiving alphabeta-depleted stem cell boosts increased their levels of
      white blood cells, platelets, and/or granulocytes 30 days after infusion. No
      signs of GVHD or other side effects were detected. A larger pool of patients with
      longer follow-up time is needed to confirm the data in this study. 

PMID- 25371911
TI  - Bone-implant contact around crestal and subcrestal dental implants submitted to
      immediate and conventional loading.
AB  - The present study aims to evaluate the influence of apicocoronal position and
      immediate and conventional loading in the percentage of bone-implant contact
      (BIC). Thus, 36 implants were inserted in the edentulous mandible from six dogs.
      Three implants were installed in each hemimandible, in different positions in
      relation to the ridge: Bone Level (at crestal bone level), Minus 1 (one
      millimeter apical to crestal bone), and Minus 2 (two millimeters apical to
      crestal bone). In addition, each hemimandible was submitted to a loading
      protocol: immediate (prosthesis installed 24 hours after implantation) or
      conventional (prosthesis installed 120 days after implantation). Ninety days
      after, animals were killed, and implant and adjacent tissues were prepared for
      histometric analysis. BIC values from immediate loaded implants were 58.7%,
      57.7%, and 51.1%, respectively, while conventional loaded implants were 61.8%,
      53.8%, and 68.4%. Differences statistically significant were not observed among
      groups (P = 0.10, ANOVA test). These findings suggest that different apicocoronal
      positioning and loading protocols evaluated did not interfere in the percentage
      of bone-implant contact, suggesting that these procedures did not jeopardize
      osseointegration. 

PMID- 25371912
TI  - Carbon dioxide emissions as affected by alternative long-term irrigation and
      tillage management practices in the lower Mississippi River Valley.
AB  - Ensuring the sustainability of cultivated soils is an ever-increasing priority
      for producers in the Lower Mississippi River Valley (LMRV). As groundwater
      sources become depleted and environmental regulations become more strict,
      producers will look to alternative management practices that will ensure the
      sustainability and cost-effectiveness of their production systems. This study was
      conducted to assess the long-term (>7 years) effects of irrigation (i.e.,
      irrigated and dryland production) and tillage (conventional and no-tillage) on
      estimated carbon dioxide (CO2) emissions from soil respiration during two soybean
      (Glycine max L.) growing seasons from a wheat- (Triticum aestivum L.-) soybean,
      double-cropped production system in the LMRV region of eastern Arkansas. Soil
      surface CO2 fluxes were measured approximately every two weeks during two soybean
      growing seasons. Estimated season-long CO2 emissions were unaffected by
      irrigation in 2011 (P > 0.05); however, during the unusually dry 2012 growing
      season, season-long CO2 emissions were 87.6% greater (P = 0.044) under irrigated
      (21.9 Mg CO2 ha(-1)) than under dryland management (11.7 Mg CO2 ha(-1)). Contrary
      to what was expected, there was no interactive effect of irrigation and tillage
      on estimated season-long CO2 emissions. Understanding how long-term agricultural
      management practices affect soil respiration can help improve policies for soil
      and environmental sustainability.

PMID- 25371910
TI  - Immunomodulation by Trypanosoma cruzi: toward understanding the association of
      dendritic cells with infecting TcI and TcII populations.
AB  - Dendritic cells (DCs) are major immune components, and depending on how these
      cells are modulated, the protective host immune response changes drastically.
      Trypanosoma cruzi is a parasite with high genetic variability and modulates DCs
      by interfering with their capacity for antigen recognition, migration, and
      maturation. Despite recent efforts, the association between DCs and T. cruzi I
      (TcI) and TcII populations is unknown. Herein, it was demonstrated that AQ1.7 and
      MUTUM TcI strains present low rates of invasion of bone marrow-derived DCs,
      whereas the 1849 and 2369 TcII strains present higher rates. Whereas the four
      strains similarly induced the expression of PD-L1, the production and expression
      of IL-10 and TLR-2, respectively, in DCs were differentially increased. The
      production of TNF-alpha, IL-12, IL-6, and CCL2 and the expression of CD40, CD80,
      MHC-II, CCR5, and CCR7 changed depending on the strain. The 2369 strain yielded
      the most remarkable results because greater invasion correlated with an increase
      in the levels of anti-inflammatory molecules IL-10 and PD-L1 but not with a
      change in the levels of TNF-alpha, MHC-II, or CD40 molecules. These results
      suggest that T. cruzi strains belonging to different populations have evolved
      specific evasion strategies that subvert DCs and consequently the host response. 

PMID- 25371914
TI  - Influence of refractive condition on retinal vasculature complexity in younger
      subjects.
AB  - OBJECTIVE: The aim of this study was to compare the retinal vasculature
      complexity between emmetropia, and myopia in younger subjects. METHODS: A total
      of 82 patients (24.12 +/- 1.25 years) with two types of refractive conditions,
      myopia and emmetropia were enrolled in this study. Refraction data were converted
      to spherical equivalent refraction. These retinal images (right eyes) were
      obtained from NAVIS Lite Image Filing System and the vasculature complexity was
      measured by fractal dimension (D f ), quantified using a computer software
      following a standardized protocol. RESULTS: There was a significant difference (P
      < 0.05) in the value of D f between emmetropic (1.5666 +/- 0.0160) and myopic
      (1.5588 +/- 0.0142) groups. A positive correlation (rho = 0.260, P < 0.05)
      between the D f and the spherical equivalent refraction was detected in this
      study. Using a linear model, it was estimated that 6.7% of the variation in D f
      could be explained by spherical equivalent refraction. CONCLUSIONS: This study
      provides valuable findings about the effect of moderate to high myopia on the
      fractal dimension of the retinal vasculature network. These results show that
      myopic refraction in younger subjects was associated with a decrease in D f ,
      suggesting a loss of retinal vessel density with moderate to high myopia.

PMID- 25371915
TI  - Mapping soil surface macropores using infrared thermography: an exploratory
      laboratory study.
AB  - Macropores and water flow in soils and substrates are complex and are related to
      topics like preferential flow, nonequilibrium flow, and dual-continuum. Hence,
      the quantification of the number of macropores and the determination of their
      geometry are expected to provide a better understanding on the effects of pores
      on the soil's physical and hydraulic properties. This exploratory study aimed at
      evaluating the potential of using infrared thermography for mapping macroporosity
      at the soil surface and estimating the number and size of such macropores. The
      presented technique was applied to a small scale study (laboratory soil flume). 

PMID- 25371916
TI  - Supporting the process of removing humic substances on activated carbon.
AB  - This study is focused on biosorption process used in water treatment. The process
      has a number of advantages and a lot of research has been done into its
      intensification by means of ultrasonic modification of solutions. The study
      carried out by the authors leads to the conclusion that sonication of organic
      solutions allows for extension of the time of operation of carbon beds. For the
      analysis of the results obtained during the sorption of humic substances (HS)
      from the solution dependencies UV/UV0 or DOC/DOC0 were used. In comparative
      studies the effectiveness of sorption and sonosorption (UV/UV0) shows that the
      share of ultrasounds (US) is beneficial for extension of time deposit, both at a
      flow rate HS solution equal to 1 m/h and 5 m/h. Analysis of the US impact
      sorption on HS sorption in a biological fluidized bed, both prepared from
      biopreparat and the activated sludge confirms the higher efficiency compared to
      sonobiosorption than biosorption. These results confirm the degree of reduction
      UV254/UV0 and DOC/DOC0 for the same processes. EMS index also confirms the
      improvement of HSbiodegradation by sludge microorganisms.

PMID- 25371913
TI  - Continuous drip flow system to develop biofilm of E. faecalis under anaerobic
      conditions.
AB  - PURPOSE: To evaluate a structurally mature E. faecalis biofilm developed under
      anaerobic/dynamic conditions in an in vitro system. METHODS: An experimental
      device was developed using a continuous drip flow system designed to develop
      biofilm under anaerobic conditions. The inoculum was replaced every 24 hours with
      a fresh growth medium for up to 10 days to feed the system. Gram staining was
      done every 24 hours to control the microorganism purity. Biofilms developed under
      the system were evaluated under the scanning electron microscope (SEM). RESULTS:
      SEM micrographs demonstrated mushroom-shaped structures, corresponding to a
      mature E. faecalis biofilm. In the mature biofilm bacterial cells are totally
      encased in a polymeric extracellular matrix. CONCLUSIONS: The proposed in vitro
      system model provides an additional useful tool to study the biofilm concept in
      endodontic microbiology, allowing for a better understanding of persistent root
      canal infections.

PMID- 25371918
TI  - Differentiation by random amplified polymorphic DNA-polymerase chain reaction
      (RAPD-PCR) of Candida albicans isolated from upper respiratory tract in patients
      with non-small cell lung cancer.
AB  - Cancer patients are predisposed to fungal infections caused by Candida albicans,
      especially to oral or respiratory tract candidiasis. The aim of this study was to
      estimate genetic diversity by RAPD-PCR (random amplified polymorphic DNA
      polymerase chain reaction) of C. albicans isolated from upper respiratory tract
      of 100 patients with non-small cell lung cancer. Among 52 strains, 34 genotypes
      were defined. 10 clusters comprising 28 (53.85%) isolates with similarity
      coefficient >= 80% were formed. The remaining 24 (46.15%) isolates represented
      individual genotypes. The RAPD-PCR technique revealed genomic variability within
      C. albicans isolated from upper respiratory tract of the cancer patients. 

PMID- 25371917
TI  - Antimicrobial resistance in Rhodococcus equi.
AB  - Rhodococcus equi is an important etiologic agent of respiratory- and non
      respiratory tract infections, diseases of animals and humans. Therapy includes
      the use of various group of chemotherapeutic agents, however resistance
      acquirement is quite common. To date there is no preferred treatment protocol for
      infections caused by isolates resistant to macrolides and rifampicin. The
      resistance acquirement is a result of many molecular mechanisms, some of which
      include alterations in the cell envelope composition and structure, activity of
      the efflux pumps, enzymatic destruction or inactivation of antibiotics, and
      changes in the target site. This paper contains an overview of antimicrobial
      susceptibility of R. equi, and explains the possible molecular mechanisms
      responsible for antimicrobial resistance in this particular microorganism. 

PMID- 25371919
TI  - Characterization of recombinant expression of Bombyx mori bidensovirus ns1 using
      a modified vector.
AB  - ns1 gene of Bombyx mori bidensovirus (BmBDV) consisted of 951 nucleotides
      encoding a deduced 316-amino aicd protein. In this study, the gene was cloned and
      fused in frame with a N-terminal 6*His tag under control of the polyhedrin
      promoter, which was transposed into the mini-attTn7 locus of a modified
      baculovirus vector. Transfection of Sf-9 cells with the resulting recombinant DNA
      was performed to prepare recombinant virus and the resultant supernatant of
      transfection with fluorescent signal was harvested. Western blot analysis
      revealed that NS1 protein was successfully expressed in Sf9 cells infected with
      the recombinant virus and was confirmed by LC-MS/MS analysis. Moreover, the
      expressed NS1 is a phosphorylated protein and the phosphorylation site is Thr
      184. These results showed that the activity of BmBDV NS1 may be regulated by
      phosphorylation. 

PMID- 25371920
TI  - Retraction notice to: "Design, synthesis, and antioxidant potency of novel alpha
      tocopherol analogues in isolated membranes and intact cells" [Free Radical
      Biology & Medicine 44(2008)1452-1464].

PMID- 25371921
TI  - Retraction notice to: "Redox regulation of 7-ketocholesterol-induced apoptosis by
      beta-carotene in human macrophages" [Free Radical Biology& Medicine 42 (2007)1579
      1590].

PMID- 25371922
TI  - Expanding the electrotherapeutic toolkit: a perspective on transcranial pulsating
      electromagnetic fields (T-PEMF).

PMID- 25371924
TI  - Student ambassador report for the 14th Annual Chemometrics in Analytical
      Chemistry conference.

PMID- 25371923
TI  - Recent advances in animal model experimentation in autism research.
AB  - OBJECTIVE: Autism, a lifelong neuro-developmental disorder is a uniquely human
      condition. Animal models are not the perfect tools for the full understanding of
      human development and behavior, but they can be an important place to start. This
      review focused on the recent updates of animal model research in autism. METHODS:
      We have reviewed the publications over the last three decades, which are related
      to animal model study in autism. RESULTS: Animal models are important because
      they allow researchers to study the underlying neurobiology in a way that is not
      possible in humans. Improving the availability of better animal models will help
      the field to increase the development of medicines that can relieve disabling
      symptoms. Results from the therapeutic approaches are encouraging remarkably,
      since some behavioral alterations could be reversed even when treatment was
      performed on adult mice. Finding an animal model system with similar behavioral
      tendencies as humans is thus vital for understanding the brain mechanisms,
      supporting social motivation and attention, and the manner in which these
      mechanisms break down in autism. The ongoing studies should therefore increase
      the understanding of the biological alterations associated with autism as well as
      the development of knowledge-based treatments therapy for those struggling with
      autism. CONCLUSION: In this review, we have presented recent advances in research
      based on animal models of autism, raising hope for understanding the disease
      biology for potential therapeutic intervention to improve the quality of life of
      autism individuals.

PMID- 25371925
TI  - Near-infrared spectroscopy in China.

PMID- 25371926
TI  - Cognitive approach to teaching percutaneous coronary intervention.

PMID- 25371927
TI  - The challenge of delivering reliable science and guidelines: opportunities for
      all to participate.
AB  - Erroneous research results have potential for harm far beyond the patients
      recruited into the study, because the leverage of leadership permits them to
      alter behaviour of thousands of clinicians for many years. Medical research does
      not yet have as well-developed and rapid-responding safety systems as other
      spheres where lives are at stake. As doctors we would all leap to assist in a
      medical emergency for a patient not formally under our care. Yet, when problems
      occur in clinical research, we do not yet have good mechanisms to all work
      together quickly and decisively to improve patient safety. In this article we
      describe how each of us, regardless of our role, can (and perhaps should) take
      active steps to support delivery of reliable science for patient care.

PMID- 25371928
TI  - ["A network platform for interested radiologists" - future visions and
      implementation].

PMID- 25371929
TI  - [In Process Citation].

PMID- 25371930
TI  - [In Process Citation].

PMID- 25371931
TI  - The author response.

PMID- 25371932
TI  - Neuromechanical coupling in the regulation of muscle tone and   joint stiffness.
AB  - The ability of the nervous system to accommodate changes to joint mechanics is
      crucial in the maintenance of joint stability and the prevention of injury. This
      neuromechanical coupling is achieved through several mechanisms such as the
      central and peripheral regulation of muscle tone and subsequent alterations to
      joint stiffness. Following joint injury, such as a ligamentous sprains, some
      patients develop functional instability or require surgery to stabilize the
      joint, while others are able to cope and display limited impairments. Several
      researchers have attempted to explain these divergent outcomes, although research
      using proprioceptive tasks and quantifying reaction times has led to equivocal
      results. Recent innovations have allowed for the simultaneous measurement of
      mechanical and nervous system function among these subsets. The intent of this
      review was to explore the relationships between joint stiffness and nervous
      system function, and how it changes following injury. By better understanding
      these mechanisms, researchers and clinicians may better develop and implement
      rehabilitation protocols to target individual deficits among injured populations.

PMID- 25371933
TI  - Kinematic analysis of the wheelchair tennis serve: Implications   for
      classification.
AB  - The aim of the present study was to assess the validity of the classification
      system used in Open-class wheelchair tennis by investigating the relationship
      between post-impact ball velocity in the serve (measured using a sports radar
      gun) and the severity of impairment. Shoulder and wrist angles at the instant of
      ball impact were also estimated from 2D motion analysis. Forty-three nationally
      ranked Italian Open-class wheelchair tennis players were assigned to four groups
      (A-D) according to descending level of activity limitation. Ten successful flat
      serves (WFSs) and 10 successful kick serves (WKSs) for each player were recorded.
      One-way ANOVA showed that the severity of impairment significantly (P < 0.05)
      affected post-impact ball velocity and shoulder angle at the instant of ball
      impact. Furthermore, the mean value of post-impact ball velocity in WFS increased
      from group A to group D, i.e., with descending level of activity limitation. The
      results of this cross-sectional study indicate that the severity of impairment
      per se is associated with velocity of the wheelchair tennis serve, suggesting
      that the current classification is flawed in that it overlooks the impact of
      severity of impairment on players' performance.

PMID- 25371934
TI  - Using the prototype willingness model to predict doping in sport.
AB  - To enable preventive measures to be designed, it is important to identify
      modifiable distal and proximal factors underlying doping behavior. This study
      investigated aspects of the prototype willingness model in relation to doping. A
      cross-sectional study was conducted involving 729 competitive athletes. Following
      ethical approval, athletes (mean age = 28.8 +/- 10.1 years; 63% male) completed
      an online questionnaire, which assessed doping-related attitudes, norms,
      prototype perceptions, outcome expectancies, and behavioral willingness. Using
      hierarchical multiple regression analysis, 54.4% of the total variance in
      willingness to dope was explained. Specifically, past doping, attitudes, and
      favorability of performance enhancing substance user prototypes were the
      strongest unique predictors of willingness to dope. Athletes appeared most
      willing to dope if they were to suffer an injury, a dip in performance, or think
      others are doping and getting away with it. National-level athletes displayed
      significantly greater willingness to dope (Kruskal-Wallis gamma2 = 35.9, P <
      0.001) and perceived themselves as significantly more similar to a doper (Kruskal
      Wallis gamma2 = 13.4, P = 0.004) than athletes competing at any other level. The
      findings highlight the importance of extending anti-doping provision beyond elite
      level sport and the need to target athletes' doping-related perceptions.

PMID- 25371935
TI  - Reproductive sciences in animal conservation. Foreword.

PMID- 25371936
TI  - Impact of change in delivery practice on neonatal and maternal outcomes in cases
      of significant congenital heart disease.
AB  - OBJECTIVE: Because of data published in 2009 demonstrating improved outcomes
      among early- vs. late-term infants,practice shifted toward delivering infants at
      later gestational ages. We examined the effects of this change on neonates with
      congenital heart disease. DESIGN: This was a retrospective cohort study. Neonates
      with congenital heart disease born between 2004 and 2008 were compared with those
      born in 2010. Patients born in 2009, considered to be a transitional year, were
      excluded. SETTING: Our study was conducted at a tertiary care level 4 neonatal
      intensive care unit with comprehensive cardiac service. PATIENTS: Study subjects
      consisted of neonates with significant congenital heart disease admitted between
      2004 and 2010. OUTCOME MEASURES: Outcomes measures consisted of mode of delivery,
      length of stay, neonatal morbidity, and mortality. RESULTS: There were 878
      infants with congenital heart disease born in 2004-2008 and 124 in 2010. The mean
      gestational age was higher in 2010 than in 2004-2008 (38.4 +/- 1.9 vs. 37.8 +/-
      2.3 weeks, P = .001), and there were fewer preterm births in 2010 compared with
      2004-2008 (P = .003, odds ratio [OR] = 0.4). Mean birth weight was also higher in
      2010 (3134 +/- 675 vs. 2975 +/- 599 g, P = .008). In 2010, less than half as many
      infants were born via scheduled induction (P < .001, OR = 0.2) or scheduled
      cesarean delivery (P = .002, OR = 0.4) as in 2004-2008. However, in 2010, there
      were more urgent inductions (P = .002, OR = 3.1), cesarean deliveries after labor
      (P = .01, OR = 2.2),and unplanned cesarean deliveries in general (P = .02, OR =
      1.7) compared with 2004-2008. In 2010, neonates were less likely to require
      preoperative vasopressors (P = .002), but there were no differences in 5 minutes
      APGAR,antibiotic administration, preoperative intubation, median length of stay,
      or mortality compared with 2004-2008.Conclusions. Despite increased gestational
      age and birth weight following the shift in delivery practice, there was no
      difference in length of stay, neonatal morbidity, or mortality in infants with
      congenital heart disease. The resultant increase in urgent cesarean delivery and
      urgent inductions may confer additional maternal morbidity.

PMID- 25371938
TI  - Preface.

PMID- 25371937
TI  - Epilepsy. Foreword.

PMID- 25371939
TI  - [Not Available].

PMID- 25371940
TI  - Personal reflections of our perinatal research group in the early years.
      Foreword.

PMID- 25371942
TI  - Reducing radiation exposure in spinal surgery.

PMID- 25371941
TI  - The argument against surgery for symptomatic low back pain.

PMID- 25371943
TI  - Pre-symptomatic cervical myelopathy: should we operate or should we observe? What
      is the chance of spinal cord injury from an accident?

PMID- 25371944
TI  - Minimally invasive surgery for thoracic and lumbar spinal fractures: rationale
      for treatment.

PMID- 25371945
TI  - Minimally invasive transforaminal interbody fusion: a single center experience.

PMID- 25371946
TI  - Does minimally invasive surgery decrease the rate of adjacent segment
      degeneration?

PMID- 25371947
TI  - Does cervical arthroplasty reduce the rate of adjacent segment disease?

PMID- 25371948
TI  - State of art of recurrent lumbar disk herniation, interspinous and interlumbar
      fusions.

PMID- 25371949
TI  - Do stand alone cervical interbody spacers pose any advantage over plate and
      screws?

PMID- 25371950
TI  - The impact of complications following cervical spine surgery: a systematic
      review.

PMID- 25371951
TI  - Grade I lumbar degenerative spondylolisthesis: do we always need fusion with
      bilateral screws and rods?

PMID- 25371952
TI  - Conservative management of degenerative disorders of the spine.

PMID- 25371953
TI  - Posterior surgery or lateral lumbar interbody fusion for degenerative deformity?
      Comparative data.

PMID- 25371954
TI  - Minimally invasive surgery for adult spinal deformity.

PMID- 25371955
TI  - How do interbody devices affect sagittal plane alignment.

PMID- 25371956
TI  - Reducing surgical site infection in lumbar surgery? What is the comparative
      effectiveness data?

PMID- 25371957
TI  - Surgical challenges of fixed spine: how to restore a fixed imbalance?

PMID- 25371958
TI  - Laminoplasty and laminectomy in cervical stenotic myelopathy: allies not enemies.

PMID- 25371959
TI  - Management of vascular and ureteral complications after lumbar discectomy. .

PMID- 25371960
TI  - Invasive and mini-invasive lumbar fusions. Does exist a state of art? An enigma
      in search of solutions.

PMID- 25371961
TI  - Anesthesia in the degenerative pathology of the spine.

PMID- 25371962
TI  - Early postoperative extramedullary MRI signal changes after ACDF:
      misinterpretations can be dangerous and misleading. Case report and review of the
      literature.

PMID- 25371964
TI  - A tunable ZnO/electrolyte heterojunction for a self-powered photodetector.
AB  - A self-powered photodetector was fabricated by taking advantage of the band
      bending at the ZnO/electrolyte interface. And a 48% performance enhancement was
      achieved with the introduction of 0.15% compressive strain due to the generation
      of piezopolarization charges. This result could be extended to other solid-liquid
      reactions, such as photoelectrochemical or photocatalytic processes. 

PMID- 25371963
TI  - Health-Based Payment for HIV/AIDS in Medicaid Managed Care Programs.
AB  - In recent years, State Medicaid programs have begun adopting health-based payment
      systems to help ensure quality care for people living with human immunodeficiency
      virus (HIV) and acquired immunodeficiency syndrome (AIDS), and to ensure equity
      for the managed care organizations (MCOs) in which these people are enrolled. In
      this article, the authors discuss reasons why such payment systems are needed and
      describe AIDS-specific capitation rates that have been adopted in several State
      Medicaid waiver programs. The authors also examine comprehensive risk-adjustment
      systems both within Medicaid and outside the program. Several research questions
      needing further work are discussed.

PMID- 25371965
TI  - Reliability and validity of a talent identification test battery for seated and
      standing Paralympic throws.
AB  - Paralympic throwing events for athletes with physical impairments comprise seated
      and standing javelin, shot put, discus and seated club throwing. Identification
      of talented throwers would enable prediction of future success and promote
      participation; however, a valid and reliable talent identification battery for
      Paralympic throwing has not been reported. This study evaluates the reliability
      and validity of a talent identification battery for Paralympic throws.
      Participants were non-disabled so that impairment would not confound analyses,
      and results would provide an indication of normative performance. Twenty-eight
      non-disabled participants (13 M; 15 F) aged 23.6 years (+/-5.44) performed five
      kinematically distinct criterion throws (three seated, two standing) and nine
      talent identification tests (three anthropometric, six motor); 23 were tested a
      second time to evaluate test-retest reliability. Talent identification test
      retest reliability was evaluated using Intra-class Correlation Coefficient (ICC)
      and Bland-Altman plots (Limits of Agreement). Spearman's correlation assessed
      strength of association between criterion throws and talent identification tests.
      Reliability was generally acceptable (mean ICC = 0.89), but two seated talent
      identification tests require more extensive familiarisation. Correlation strength
      (mean rs = 0.76) indicated that the talent identification tests can be used to
      validly identify individuals with competitively advantageous attributes for each
      of the five kinematically distinct throwing activities. Results facilitate
      further research in this understudied area.

PMID- 25371966
TI  - Use of PER977 to reverse the anticoagulant effect of edoxaban.

PMID- 25371967
TI  - Testing the role of charge and structure on the stability of peptide-porphyrin
      complexes.
AB  - This study aims to extend a structural and biophysical understanding of a coiled
      coil based peptide model system that serves as a scaffold for the anionic
      porphyrin, TPPS4. This is part of an ongoing biomaterials effort to create
      photoelectronically active mesoscale fibrils for surface deposition and
      characterization of conductivity properties. The goals are two-fold: (1) to
      explore optimal basic side-chain moieties for tight binding to TPPS4 and (2) to
      test the binding of various metalated TPPS4 derivatives to our peptide model
      system. The latter goal is to control the electronic and redox properties of the
      fibrillar biomaterials. A soluble version of the peptide biomaterial was used in
      order to probe binding and to extract thermodynamically rigorous equilibrium
      binding constants. UV-visible spectroscopy and circular dichroism
      spectropolarimtery are used to measure the effects of binding on the Soret band
      of the porphyrin and the helical signal of the peptide, respectively. For the
      first study, it was found that lysine, ornithine, and arginine are equally robust
      at engaging TPPS4 with low micromolar binding affinity. In the case of the
      metalated porphyrins, submicromolar binding affinity was observed for Cu(II),
      Ni(II), and Pd(II). The ability of these metalated porphyrins to bind with high
      affinity is dependent largely on structural perturbations of the porphyrin
      molecule, rather than on induced electronic effects.

PMID- 25371968
TI  - Real-time microfluidic recombinase polymerase amplification for the toxin B gene
      of Clostridium difficile on a SlipChip platform.
AB  - Clostridium difficile is one of the key bacterial pathogens that cause infectious
      diarrhoea both in the developed and developing world. Isothermal nucleic acid
      amplification methods are increasingly used for identification of toxinogenic
      infection by clinical labs. For this purpose, we developed a low-cost
      microfluidic platform based on the SlipChip concept and implemented real-time
      isothermal recombinase polymerase amplification (RPA). The on-chip RPA assay
      targets the Clostridium difficile toxin B gene (tcdB) coding for toxin B, one of
      the proteins responsible for bacterial toxicity. The device was fabricated in
      clear acrylic using rapid prototyping methods. It has six replicate 500 nL
      reaction wells as well as two sets of 500 nL control wells. The reaction can be
      monitored in real-time using exonuclease fluorescent probes with an initial
      sample volume of as little as 6.4 MUL. We demonstrated a limit of detection of
      1000 DNA copies, corresponding to 1 fg, at a time-to-result of <20 minutes. This
      miniaturised platform for pathogen detection has potential for use in resource
      limited environments or at the point-of-care because of its ease of use and low
      cost, particularly if combined with preserved reagents. 

PMID- 25371969
TI  - Evidence of Innovative Uses of Performance Measures Among Purchasers.
AB  - Purchasers are interested in quality of care and performance information for a
      number of reasons including helping purchasers to make value-based purchasing
      decisions, holding health plans and providers accountable, and monitoring the
      care received by enrollees. Interviews with purchasers were conducted in several
      geographic areas. Purchasers included in the study were large employers, business
      coalitions, and governments. Objectives of the study were to determine what
      performance measurement initiatives large purchasers have established, to explore
      how large purchasers use the results of their performance measurement
      initiatives, and to examine how these purchasers interact and share information
      in their respective markets.

PMID- 25371970
TI  - Hydration status regulates sodium flux and inflammatory pathways through
      epithelial sodium channel (ENaC) in the skin.
AB  - Although it is known that the inflammatory response that results from disruption
      of epithelial barrier function after injury results in excessive scarring, the
      upstream signals remain unknown. It has also been observed that epithelial
      disruption results in reduced hydration status and that the use of occlusive
      dressings that prevent water loss from wounds decreases scar formation. We
      hypothesized that hydration status changes sodium homeostasis and induces sodium
      flux in keratinocytes, which result in activation of pathways responsible for
      keratinocyte-fibroblast signaling and ultimately lead to activation of
      fibroblasts. Here, we demonstrate that perturbations in epithelial barrier
      function lead to increased sodium flux in keratinocytes. We identified that
      sodium flux in keratinocytes is mediated by epithelial sodium channels (ENaCs)
      and causes increased secretion of proinflammatory cytokines, which activate
      fibroblast via the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway.
      Similar changes in signal transduction and sodium flux occur by increased sodium
      concentration, which simulates reduced hydration, in the media in epithelial
      cultures or human ex vivo skin cultures. Blockade of ENaC, prostaglandin
      synthesis, or PGE2 receptors all reduce markers of fibroblast activation and
      collagen synthesis. In addition, employing a validated in vivo excessive scar
      model in the rabbit ear, we demonstrate that utilization of either an ENaC
      blocker or a COX-2 inhibitor results in a marked reduction in scarring. Other
      experiments demonstrate that the activation of COX-2 in response to increased
      sodium flux is mediated through the PIK3/Akt pathway. Our results indicate that
      ENaC responds to small changes in sodium concentration with inflammatory
      mediators and suggest that the ENaC pathway is a potential target for a strategy
      to prevent fibrosis.

PMID- 25371972
TI  - Gallium maltolate inhibits human cutaneous T-cell lymphoma tumor development in
      mice.
AB  - Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of non
      Hodgkin's lymphoma characterized by an accumulation of malignant CD4 T cells in
      the skin. The group IIIa metal salt, gallium nitrate, is known to have
      antineoplastic activity against B-cell lymphoma in humans, but its activity in
      CTCLs has not been elaborated in detail. Herein, we examined the antineoplastic
      efficacy of a gallium compound, gallium maltolate (GaM), in vitro and in vivo
      with murine models of CTCLs. GaM inhibited cell growth and induced apoptosis of
      cultured CTCL cells. In human CTCL xenograft models, peritumoral injection of GaM
      limited the growth of CTCL cells, shown by fewer tumor formations, smaller tumor
      sizes, and decreased neovascularization in tumor microenvironment. To identify
      key signaling pathways that have a role in GaM-mediated reduction of tumor
      growth, we analyzed inflammatory cytokines, as well as signal transduction
      pathways in CTCL cells treated by GaM. IFN-gamma-induced chemokines and IL-13
      were found to be notably increased in GaM-treated CTCL cells. However,
      immunosuppressive cytokines, such as IL-10, were decreased with GaM treatment.
      Interestingly, both oxidative stress and p53 pathways were involved in GaM
      induced cytotoxicity. These results warrant further investigation of GaM as a
      therapeutic agent for CTCLs. 

PMID- 25371973
TI  - A rare (3,4,5)-connected metal-organic framework featuring an unprecedented 1D +
      2D -> 3D self-interpenetrated array and an O-atom lined pore surface: structure
      and controlled drug release.
AB  - A rare (3,4,5)-connected self-interpenetrated metal-organic framework with an O
      atom lined pore surface has been constructed from Zn(II) and H4L (H4L = 5,5'
      (1,3,6,8-tetraoxobenzo[lmn][3,8]phenanthroline-2,7(1H,3H,6H,8H)diyl)
      diisophthalic acid), which features an unprecedented 1D + 2D -> 3D self
      interpenetrated array and shows good controlled drug release properties.

PMID- 25371971
TI  - Mitochondrial function in murine skin epithelium is crucial for hair follicle
      morphogenesis and epithelial-mesenchymal interactions.
AB  - Here, we studied how epithelial energy metabolism impacts overall skin
      development by selectively deleting intraepithelial mtDNA in mice by ablating a
      key maintenance factor (Tfam(EKO)), which induces loss of function of the
      electron transport chain (ETC). Quantitative (immuno)histomorphometry
      demonstrated that Tfam(EKO) mice showed significantly reduced hair follicle (HF)
      density and morphogenesis, fewer intrafollicular keratin15+ epithelial progenitor
      cells, increased apoptosis, and reduced proliferation. Tfam(EKO) mice also
      displayed premature entry into (aborted) HF cycling by apoptosis-driven HF
      regression (catagen). Ultrastructurally, Tfam(EKO) mice exhibited severe HF
      dystrophy, pigmentary abnormalities, and telogen-like condensed dermal papillae.
      Epithelial HF progenitor cell differentiation (Plet1, Lrig1 Lef1, and beta
      catenin), sebaceous gland development (adipophilin, Scd1, and oil red), and key
      mediators/markers of epithelial-mesenchymal interactions during skin
      morphogenesis (NCAM, versican, and alkaline phosphatase) were all severely
      altered in Tfam(EKO) mice. Moreover, the number of mast cells, major
      histocompatibility complex class II+, or CD11b+ immunocytes in the skin
      mesenchyme was increased, and essentially no subcutis developed. Therefore, in
      contrast to their epidermal counterparts, pilosebaceous unit stem cells depend on
      a functional ETC. Most importantly, our findings point toward a frontier in skin
      biology: the coupling of HF keratinocyte mitochondrial function with the
      epithelial-mesenchymal interactions that drive overall development of the skin
      and its appendages.

PMID- 25371974
TI  - Frequency-encoded MRI-CEST agents based on paramagnetic liposomes/RBC aggregates.
AB  - Paramagnetic liposomes containing Dy-HPDO3A in their inner water compartment and
      carrying a residual positive charge on their outer surface have been
      electrostatically bound to the membrane of red blood cells (RBCs). These
      aggregates yield two chemical exchange saturation transfer (CEST) pools
      represented by liposomal water protons (LipoCEST) and cytoplasmatic water protons
      (ErythroCEST), respectively. The absorption frequencies of the two pools fall at
      the negative and positive side of the solvent water resonance as expected from
      the dipolar (LipoCEST) and BMS (bulk magnetic susceptibility) (ErythroCEST)
      origin of the paramagnetic induced shift of their water protons resonances,
      respectively. In vivo magnetic resonance imaging (MRI) shows that the
      liposomes/RBC aggregates report about the vascular volume whereas the residual
      LipoCEST effect informs about the presence of released liposomes in the region of
      interest (ROI). Besides being an innovative blood cell labeling for MRI, the
      LipoCEST/RBC aggregates provide a route to improve the circulation lifetime of
      the liposomes and the CEST procedure allows assessing the deassembly of the
      aggregates and accumulation of the liposomes in the ROI. 

PMID- 25371975
TI  - All-payer ratesetting: Down but not out.
AB  - In the United States, when the cost-containment paradigm shifted from regulation
      to competition, all-payer hospital ratesetting went out of favor. After reviewing
      the published literature and supplementing the existing literature with more
      current information, the author concludes that all-payer ratesetting is able to
      meet its multiple objectives of cost containment, reduction of the amount of cost
      shifting, improvement of access to the uninsured, and increased productivity. At
      the same time, all-payer ratesetting has not stifled the diffusion of competitive
      health care systems or new technology, and any impact on length of stay,
      admissions, and quality of care is small, if it exists at all.

PMID- 25371976
TI  - Logistic regression function for detection of suspicious performance during
      baseline evaluations using concussion vital signs.
AB  - This study utilized logistic regression to determine whether performance patterns
      on Concussion Vital Signs (CVS) could differentiate known groups with either
      genuine or feigned performance. For the embedded measure development group (n =
      174), clinical patients and undergraduate students categorized as feigning
      obtained significantly lower scores on the overall test battery mean for the CVS,
      Shipley-2 composite score, and California Verbal Learning Test-Second Edition
      subtests than did genuinely performing individuals. The final full model of 3
      predictor variables (Verbal Memory immediate hits, Verbal Memory immediate
      correct passes, and Stroop Test complex reaction time correct) was significant
      and correctly classified individuals in their known group 83% of the time
      (sensitivity = .65; specificity = .97) in a mixed sample of young-adult clinical
      cases and simulators. The CVS logistic regression function was applied to a
      separate undergraduate college group (n = 378) that was asked to perform
      genuinely and identified 5% as having possibly feigned performance indicating a
      low false-positive rate. The failure rate was 11% and 16% at baseline cognitive
      testing in samples of high school and college athletes, respectively. These
      findings have particular relevance given the increasing use of computerized test
      batteries for baseline cognitive testing and return-to-play decisions after
      concussion. 

PMID- 25371977
TI  - Opening Remarks.
AB  - These opening remarks were made by Max Sherman, Dean of the Lyndon B. Johnson
      School of Public Affairs, Austin, Texas, on May 6, 1996, as an introduction to
      the proceedings of the Symposium "Medicare: Advancing Towards the 21st Century."

PMID- 25371978
TI  - Health Data File: Overview and methodology.
AB  - This international compendium from the Organization for Economic Cooperation and
      Development Secretariat contains available data for the 24 Member countries for
      1960 through 1987. The Federal Republic of Germany is listed as Germany. Tables
      are presented for expenditure on health, health care pricing trends, social
      protection and public participation, utilization of medical services and
      available personnel resources, selected variations in common medical care
      practice, selected health status indicators, and demographic and general economic
      background data. There may be some inconsistencies between the data presented in
      the articles in this issue and those in this data compendium. The articles were
      based on earlier versions of the Health Data File. As a result, revisions to the
      data in a number of countries, including Canada, France, Germany, and Italy, are
      not reflected in the articles. However, the changes are relatively minor and do
      not affect the results presented in the articles in any substantive way.

PMID- 25371979
TI  - Sensitivity of coded aperture Raman spectroscopy to analytes beneath turbid
      biological tissue and tissue-simulating phantoms.
AB  - Traditional slit-based spectrometers have an inherent trade-off between spectral
      resolution and throughput that can limit their performance when measuring diffuse
      sources such as light returned from highly scattering biological tissue.
      Recently, multielement fiber bundles have been used to effectively measure
      diffuse sources, e.g., in the field of spatially offset Raman spectroscopy, by
      remapping the source (or some region of the source) into a slit shape for
      delivery to the spectrometer. Another approach is to change the nature of the
      instrument by using a coded entrance aperture, which can increase throughput
      without sacrificing spectral resolution.In this study, two spectrometers, one
      with a slit-based entrance aperture and the other with a coded aperture, were
      used to measure Raman spectra of an analyte as a function of the optical
      properties of an overlying scattering medium. Power-law fits reveal that the
      analyte signal is approximately proportional to the number of transport mean free
      paths of the scattering medium raised to a power of -0.47 (coded aperture
      instrument) or -1.09 (slit-based instrument). These results demonstrate that the
      attenuation in signal intensity is more pronounced for the slit-based instrument
      and highlight the scattering regimes where coded aperture instruments can provide
      an advantage over traditional slit-based spectrometers.

PMID- 25371980
TI  - Monitoring the reduced scattering coefficient of bone tissues on the trajectory
      of pedicle screw placement using near-infrared spectroscopy.
AB  - Pedicle screw (PS) fixation has been widely used for spine diseases. Scientists
      and clinicians employ several approaches to navigate PS during operation. We have
      demonstrated the feasibility of monitoring the reduced scattering coefficient
      (MU's) on the trajectory of PS using near-infrared spectroscopy (NIRS). To
      perform the in-vitro monitoring, an NIRS measurement system was introduced and
      the reduced scattering coefficients of different sites in porcine pedicle were
      accurately deduced from the spectrum. Moreover, the changes of the reduced
      scattering coefficient along the different paths were studied. The results show
      reduced scattering coefficients on different regions of bones can be
      significantly distinguished. Furthermore, monitoring experiments along different
      paths confirmed that a reduced scattering coefficient would change versus the
      depth of puncture in pedicles. Thus, the proposed monitoring system based on NIRS
      provides a potential for guiding PS during operation.

PMID- 25371981
TI  - Isomeric C12-alkamides from the roots of Echinacea purpurea improve basal and
      insulin-dependent glucose uptake in 3T3-L1 adipocytes.
AB  - Echinacea purpurea has been used in traditional medicine as a remedy for the
      treatment and prevention of upper respiratory tract infections and the common
      cold. Recent investigations have indicated that E. purpurea also has an effect on
      insulin resistance. A dichloromethane extract of E. purpurea roots was found to
      enhance glucose uptake in adipocytes and to activate peroxisome proliferator
      activated receptor gamma. The purpose of the present study was to identify the
      bioactive compounds responsible for the potential antidiabetic effect of the
      dichloromethane extract using a bioassay-guided fractionation approach. Basal and
      insulin-dependent glucose uptake in 3T3-L1 adipocytes were used to assess the
      bioactivity of extract, fractions and isolated metabolites. A peroxisome
      proliferator-activated receptor gamma transactivation assay was used to determine
      the peroxisome proliferator-activated receptor gamma activating properties of the
      extract, active fractions and isolated metabolites. Two novel isomeric dodeca
      2E,4E,8Z,10E/Z-tetraenoic acid 2-methylbutylamides together with two known C12
      alkamides and alpha-linolenic acid were isolated from the active fractions. The
      isomeric C12-alkamides were found to activate peroxisome proliferator-activated
      receptor gamma, to increase basal and insulin-dependent glucose uptake in
      adipocytes in a dose-dependent manner, and to exhibit characteristics of a
      peroxisome proliferator-activated receptor gamma partial agonist. 

PMID- 25371982
TI  - Diterpenes from Euphorbia piscatoria: synergistic interaction of Lathyranes with
      doxorubicin on resistant cancer cells.
AB  - Four new diterpenes were isolated from the methanolic extract of Euphorbia
      piscatoria, two ent-abietanes (1, 2) and two lathyrane-type macrocyclic
      diterpenes (3, 4), along with three known diterpenes (5-7). Their structures were
      characterized by spectroscopic methods, mainly 1D and 2D NMR ((1)H, (13)C, DEPT,
      COSY, HMBC, HMQC, and NOESY) experiments. Compound 2, with an unusual structure,
      might be considered intermediate in the biosynthesis of ent-abietane alpha,beta
      unsaturated lactones, commonly found in Euphorbia species. Therefore, a possible
      biogenetic pathway is proposed. The MDR reversal potential of macrocyclic
      diterpenes 3-5 was evaluated through a drug combination assay, using the L5178Y
      mouse T lymphoma cell line transfected with the human MDR1 gene. Compounds 3-5
      were able to enhance, synergistically, the antiproliferative activity of
      doxorubicin (combination indexes < 0.5). Moreover, compounds 1-6 were also
      assessed for their antiproliferative activity on human MDR cancer cell models,
      namely gastric, pancreatic, and colon. Weak antiproliferative activity was
      observed for compounds 1 (IC50 = 66.02 +/- 7.10 uM) and 4 (IC50 = 39.51 +/- 3.82
      uM) on the MDR gastric cell line. 

PMID- 25371984
TI  - Health Care of Vulnerable Populations Covered by Medicare and Medicaid.
AB  - This overview discusses articles published in this issue of the Health Care
      Financing Review, entitled "Health Care Needs of Vulnerable Populations."
      Articles cover the following vulnerable population subgroups: pregnant women and
      children, persons with AIDS, the disabled, and the elderly. Issues covered in
      this collection include: expenditures, demographic factors, Medicaid and Medicare
      policy, service use, medical procedures, and data collection.

PMID- 25371985
TI  - Accuracy and Bias of Race/Ethnicity Codes in the Medicare Enrollment Database.
AB  - Medicare administrative data are fairly accurate in identifying people who
      affiliate with White or Black racial groups; but less so for other race groups or
      for Hispanic/Latino origin. Some differences were found between people who were
      identified as members of these other race groups and those who were missed by the
      administrative data. Although Medicare administrative files are a useful source
      of data for analysis of disparities in health care, researchers should be careful
      to use alternate data sources to test for potential differences between
      identified and unidentified members of racial and ethnic groups in the attributes
      being studied.

PMID- 25371983
TI  - Schistosomicidal and antioxidant flavonoids from Astragalus englerianus.
AB  - Astragalus englerianus is a close relative of the traditional Chinese medicine
      plant Radix Astragali (Huang-qi) and is mainly distributed in Yunnan. It has been
      traditionally used as a substitute of "Huang-qi" for reducing fatigue and
      enhancing immunity by local folks. A phytochemical study of the methanol extract
      of the roots led to the isolation of three new flavonoids including one aurone
      (1) and two chalcones (2 and 3), as well as two known flavonoids (4 and 5). Their
      structures were elucidated based on the analyses of extensive spectroscopic data
      and comparison of their physicochemical properties. This is the first report on
      the occurrence of beta-hydroxydihydrochalcone, 2',5'-dioxygenchalcones, and 2',5'
      dioxygenaurone in the genus Astragalus. All the isolated compounds were tested in
      vitro for their schistosomicidal and antioxidant activities. Compounds 2 and 4
      showed schistosomicidal activities with worm mortality rates of 100 % within 12 h
      in a drug-containing (0.70 and 0.77 mM, respectively) RPMI 1640 medium. Compounds
      1 and 2 exhibited antioxidant activities in 2,2-diphenyl-1-(2,4,6
      trinitrophenyl)hydrazyl free radical scavenging assays, with IC50 values of 35.9
      +/- 1.1 and 12.2 +/- 1.1 uM, respectively. 

PMID- 25371986
TI  - Strategy to improve the quantitative LC-MS analysis of molecular ions resistant
      to gas-phase collision induced dissociation: application to disulfide-rich cyclic
      peptides.
AB  - Due to observed collision induced dissociation (CID) fragmentation inefficiency,
      developing sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS)
      assays for CID resistant compounds is especially challenging. As an alternative
      to traditional LC-MS/MS, we present here a methodology that preserves the intact
      analyte ion for quantification by selectively filtering ions while reducing
      chemical noise. Utilizing a quadrupole-Orbitrap MS, the target ion is selectively
      isolated while interfering matrix components undergo MS/MS fragmentation by CID,
      allowing noise-free detection of the analyte's surviving molecular ion. In this
      manner, CID affords additional selectivity during high resolution accurate mass
      analysis by elimination of isobaric interferences, a fundamentally different
      concept than the traditional approach of monitoring a target analyte's unique
      fragment following CID. This survivor-selected ion monitoring (survivor-SIM)
      approach has allowed sensitive and specific detection of disulfide-rich cyclic
      peptides extracted from plasma. 

PMID- 25371987
TI  - Bidirectional macrocyclization of peptides by double multicomponent reactions.
AB  - Increasing the diversity of peptide cyclization methods is an effective way of
      accessing new types of macrocyclic chemotypes featuring a wide variety of ring
      sizes and topologies. Multicomponent reactions (MCRs) are processes capable of
      generating great levels of molecular diversity and complexity at low synthetic
      cost. In an attempt to further exploit MCRs in the field of cyclopeptides, we
      describe a bidirectional multicomponent approach for the synthesis of N-alkylated
      macrocyclic peptides of varied sequences and cross-linking positions. The process
      relies on the execution of two Ugi reactions between peptide diacids and
      diisocyanides. Varying the amino component enabled the installation of exocyclic
      elements of diversity, while skeletal diversity was created through different
      side chain and backbone cyclizations. This procedure shows prospects for the
      rapid scanning of the chemical space of macrocyclic peptides for applications in
      chemical biology and drug discovery. 

PMID- 25371988
TI  - Piper betle leaf extracts induced human hepatocellular carcinoma Hep3B cell death
      via MAPKs regulating the p73 pathway in vitro and in vivo.
AB  - Extracts of Piper betle leaf (PBLs) are rich in bioactive compounds with
      potential chemopreventive ability. In this study, Hep3B cells which are p53 null
      were used to investigate the anti-tumor effect of PBLs in the cell and in the
      xenograft model. The results revealed that PBLs (0.1 to 1 mg mL(-1)) induced a
      dose- and time-dependent increase of cell toxicity. The underlying mechanisms as
      evidenced by flow cytometry and western blot analysis showed that PBLs triggered
      ATM, cAbl, and p73 expressions and activated JNK and p38 pathways that
      subsequently led to cell cycle arrest and mitochondria-dependent apoptosis. PBLs
      also inhibited tumor growth in Hep3B-bearing mice via inducing the MAPK-p73
      pathway. Our results demonstrated the in vitro and in vivo anti-tumor potential
      of PBLs, supporting their application as a novel chemopreventive agent for the
      treatment of human hepatocellular carcinoma (HCC) in the future via targeting the
      p73 pathway. 

PMID- 25371989
TI  - Milestones in Medicare Managed Care.
AB  - Medicare managed care has a long history, dating back to the beginning of the
      Medicare program. The role and prominence of managed care in Medicare have both
      changed over the years; though plan participation has waxed and waned, enrollment
      has grown steadily The greatest growth in Medicare managed care enrollment
      occurred in the middle to late 1990s, coinciding with the "managed care
      revolution." Enrollment growth has slowed in recent years, plan participation is
      declining, and the future of the program is not easy to predict.

PMID- 25371991
TI  - Why Medicare Part A and Part B, as Well as Medicaid?

PMID- 25371990
TI  - Purification of nanoscale electron-beam-induced platinum deposits via a pulsed
      laser-induced oxidation reaction.
AB  - Platinum-carbon deposits made via electron-beam-induced deposition were purified
      via a pulsed laser-induced oxidation reaction and erosion of the amorphous carbon
      to form pure platinum. Purification proceeds from the top down and is likely
      catalytically facilitated via the evolving platinum layer. Thermal simulations
      suggest a temperature threshold of ~485 K, and the purification rate is a
      function of the PtC5 thickness (80-360 nm) and laser pulse width (1-100 MUs) in
      the ranges studied. The thickness dependence is attributed to the ~235 nm
      penetration depth of the PtC5 composite at the laser wavelength, and the pulse
      width dependence is attributed to the increased temperatures achieved at longer
      pulse widths. Remarkably fast purification is realized at cumulative laser
      exposure times of less than 1 s.

PMID- 25371992
TI  - Immunogenicity study of Globo H analogues with modification at the reducing or
      nonreducing end of the tumor antigen.
AB  - Globo H-based therapeutic cancer vaccines have been tested in clinical trials for
      the treatment of late stage breast, ovarian, and prostate cancers. In this study,
      we explored Globo H analogue antigens with an attempt to enhance the antigenic
      properties in vaccine design. The Globo H analogues with modification at the
      reducing or nonreducing end were synthesized using chemoenzymatic methods, and
      these modified Globo H antigens were then conjugated with the carrier protein
      diphtheria toxoid cross-reactive material (CRM) 197 (DT), and combined with a
      glycolipid C34 as an adjuvant designed to induce a class switch to form the
      vaccine candidates. After Balb/c mice injection, the immune response was studied
      by a glycan array and the results showed that modification at the C-6 position of
      reducing end glucose of Globo H with the fluoro, azido, or phenyl group elicited
      IgG antibody response to specifically recognize Globo H (GH) and the GH-related
      epitopes, stage-specific embryonic antigen 3 (SSEA3) (also called Gb5) and stage
      specific embryonic antigen 4 (SSEA4). However, only the modification of Globo H
      with the azido group at the C-6 position of the nonreducing end fucose could
      elicit a strong IgG immune response. Moreover, the antibodies induced by these
      vaccines were shown to recognize GH expressing tumor cells (MCF-7) and mediate
      the complement-dependent cell cytotoxicity against tumor cells. Our data suggest
      a new potential approach to cancer vaccine development. 

PMID- 25371996
TI  - Infrared identification of proton-bound rare-gas dimers (XeHXe)+, (KrHKr)+, and
      (KrHXe)+ and their deuterated species in solid hydrogen.
AB  - Proton-bound rare-gas dimer (RgHRg)(+), in which Rg represents a rare-gas atom,
      serves as a prototypical system for proton solvation by inert-gas atoms. Until
      now, only centrosymmetric species with Rg = Ar, Kr, or Xe have been identified
      with infrared spectra. We employed electron bombardment during deposition of a
      mixture of Xe (or Kr) in p-H2 at 3.2 K to prepare (RgHRg)(+). Lines at 847.0 and
      972.1 cm(-1) are assigned as the Rg-H-Rg antisymmetric stretching (nu3) mode and
      its combination with the Rg-H-Rg symmetric stretching (nu1 + nu3) mode of
      (XeHXe)(+) in solid p-H2, respectively. Lines at 871.1 and 974.0 cm(-1) are
      assigned as the nu3 and nu1 + nu3 modes of (KrHKr)(+) in solid p-H2,
      respectively. Slightly shifted and broadened lines were observed for these
      species in solid n-H2. These results agree satisfactorily with reported
      experimental values of (XeHXe)(+) and (KrHKr)(+) in solid Xe, Kr, and Ar, and
      with the quantum-chemically predicted anharmonic vibrational wavenumbers of these
      species in the gaseous phase; the significant spectral shifts in various matrixes
      are rationalized with the proton affinities of the hosts. When a mixture of Xe
      and Kr in p-H2 was used, an additional broad feature at 1284 cm(-1) was observed
      and assigned as the nu3 mode of (KrHXe)(+) in solid p-H2. This line shifted to
      1280 cm(-1) in solid n-H2 and the corresponding line of (KrDXe)(+) was observed
      at 954 cm(-1) in n-D2. The observations of these lines are new; the wavenumbers
      significantly blue shifted from those of the centrosymmetric (RgHRg)(+) agree
      with the quantum-chemically predicted anharmonic vibrational wavenumbers of 1279
      cm(-1) for (KrHXe)(+) and 916 cm(-1) for (KrDXe)(+). Analysis of the
      computational results shows that electronic correlation effects play a much
      greater role for the asymmetric than for the symmetric species. An interpretation
      for this is provided. 

PMID- 25371997
TI  - Bifacial dye-sensitized solar cells with enhanced rear efficiency and power
      output.
AB  - Pursuing a high power conversion efficiency with no sacrifice of cost
      effectiveness has been a persistent objective for dye-sensitized solar cells
      (DSSCs). One promising solution to this impasse is increased light harvesting.
      Previous efforts in light harvesting have been made on setting blocking layers or
      reflecting layers, or adding a light harvester, resulting in tedious procedures
      without reducing the expenses. We present a mild solution strategy for
      synthesizing transparent Ru-Se alloy counter electrodes (CEs) for bifacial DSSC
      applications, displaying optimal front and rear efficiencies of 8.76% and 5.90%,
      respectively. In comparison with pristine Pt-based solar cells, the maximum power
      output has also been markedly enhanced. Moreover, fast start-up, high multiple
      start capability, and good stability are observed in the bifacial DSSCs with
      transparent Ru-Se binary alloy electrodes. The impressive efficiencies along with
      simple preparation of the cost-effective Ru-Se alloy CEs demonstrates their
      potential application in robust DSSCs. 

PMID- 25371998
TI  - Profiling the allied health staffing of Queensland Health inpatient general
      rehabilitation units.
AB  - OBJECTIVE: The purpose of this paper was to profile staffing levels for allied
      health (AH) professional and support staff in Queensland Health inpatient general
      rehabilitation services (at a given point-in-time) and compare them against
      established profession-specific standards and guidelines in order to provide a
      reference for future workforce planning for these services. METHODS: A statewide
      analysis of AH staffing in Queensland Health inpatient general rehabilitation
      services was undertaken during June-August 2011. Reported full-time equivalent
      positions (FTE) were compared to several established national and international
      benchmarks. Patient activity data was used to calculate the average length of
      stay (ALOS) and Functional Independence Measure (FIM) scores on admission.
      RESULTS: Sixteen facilities reported 202 FTE for a total of 466 general
      rehabilitation beds, with a resultant average workforce ratio of 0.43 FTE/bed.
      While several professional groups within specific services met established
      benchmarks, the majority failed to reach recommended staffing ratios. More than
      half the workforce (53%) was entry-level or consolidating clinicians. The FTE/bed
      ratios were compared against both patient ALOS and FIM scores on admission and
      showed a poor correlation. CONCLUSION: Across all included services statewide,
      there was significant variance in AH staffing levels and diversity in skill mix
      for inpatient general rehabilitation services.

PMID- 25371999
TI  - In vitro hemocompatibility and toxic mechanism of graphene oxide on human
      peripheral blood T lymphocytes and serum albumin.
AB  - Graphene oxide (GO) has shown tremendous application potential as a biomedical
      material. However, its interactions with blood components are not yet well
      understood. In this work, we assess the toxicity of pristine GO (p-GO) and
      functionalized GO (GO-COOH and GO-PEI) to primary human peripheral blood T
      lymphocytes and human serum albumin (HSA), and also study the underlying toxic
      mechanism. Our results indicate that p-GO and GO-COOH have good biocompatibility
      to T lymphocytes at the concentration below 25 MUg mL(-1), but notable
      cytotoxicity above 50 MUg mL(-1). By contrast, GO-PEI exhibits significant
      toxicity even at 1.6 MUg mL(-1). Further investigations show that although p-GO
      does not enter into the cell or damage the membrane, its presence leads to the
      increase in reactive oxygen species (ROS), moderate DNA damage, and T lymphocyte
      apoptosis. Interestingly, little effect on T lymphocyte immune response
      suppression is observed in this process despite p-GO inflicting cell apoptosis.
      The toxic mechanism is that p-GO interacts directly with the protein receptors to
      inhibit their ligand-binding ability, leading to ROS-dependent passive apoptosis
      through the B-cell lymphoma-2 (Bcl-2) pathway. Compared with p-GO, GO-COOH
      exhibits a similar toxic effect on T lymphocytes except keeping a normal ROS
      level. A proposed toxic mechanism is that GO-COOH inhibits protein receptor
      ligand binding, and passes the passive apoptosis signal to nucleus DNA through a
      ROS-independent mechanism. On the other hand, GO-PEI shows severe hematotoxicity
      to T lymphocytes by inducing membrane damage. For plasma protein HSA, the binding
      of GO-COOH results in minimal conformational change and HSA's binding capacity to
      bilirubin remains unaffected, while the binding of p-GO and GO-PEI exhibits
      strong toxicity on HSA. These findings on the interactions of two-dimensional
      nanomaterials and biological systems, along with the enquiry of the mechanisms,
      would provide essential support for further safety evaluation of the biomedical
      applications of GO. 

PMID- 25372000
TI  - Noninvasive ventilation and exercise tolerance in heart failure: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Patients with heart failure (HF) usually develop exercise
      intolerance. In this context, noninvasive ventilation (NIV) can help to increase
      physical performance. OBJECTIVE: To undertake a systematic review and meta
      analysis of randomized controlled trials that evaluated the effects of NIV on
      exercise tolerance in patients with HF. METHOD: Search Strategy: Articles were
      searched in the following databases: Physiotherapy Evidence Database (PEDro),
      Scientific Electronic Library Online (SciELO), and MEDLINE. Selection Criteria:
      This review included only randomized controlled trials involving patients with HF
      undergoing NIV, with or without other therapies, that used exercise tolerance as
      an outcome, verified by the distance travelled in the six-minute walk test
      (6MWT), VO2peak in the cardiopulmonary test, time spent in testing, and dyspnea.
      Data Collection And Analysis: The methodological quality of the studies was rated
      according to the PEDro scale. Data were pooled in fixed-effect meta-analysis
      whenever possible. RESULTS: Four studies were selected. A meta-analysis including
      18 participants showed that the use of NIV prior to the 6MWT promoted increased
      distance, [mean difference 65.29 m (95% CI 38.80 to 91.78)]. CONCLUSIONS: The use
      of NIV prior to the 6MWT in patients with HF may promote increased distance.
      However, the limited number of studies may have compromised a more definitive
      conclusion on the subject.

PMID- 25372001
TI  - Morphological aspects and Cox-2 expression after exposure to 780-nm laser therapy
      in injured skeletal muscle: an in vivo study.
AB  - BACKGROUND: The effectiveness of low-level laser therapy in muscle regeneration
      is still not well known. OBJECTIVE: To investigate the effects of laser
      irradiation during muscle healing. METHOD: For this purpose, 63 rats were
      distributed to 3 groups: non-irradiated control group (CG); group irradiated at
      10 J/cm(2) (G10); and group irradiated at 50 J/cm(2) (G50). Each group was
      divided into 3 different subgroups (n=7), and on days 7, 14 and 21 post-injury
      the rats were sacrificed. RESULTS: Seven days post-surgery, the CG showed
      destroyed zones and extensive myofibrillar degeneration. For both treated groups,
      the necrosis area was smaller compared to the CG. On day 14 post-injury, treated
      groups demonstrated better tissue organization, with newly formed muscle fibers
      compared to the CG. On the 21(st) day, the irradiated groups showed similar
      patterns of tissue repair, with improved muscle structure at the site of the
      injury, resembling uninjured muscle tissue organization. Regarding collagen
      deposition, the G10 showed an increase in collagen synthesis. In the last period
      evaluated, both treated groups showed statistically higher values in comparison
      with the CG. Furthermore, laser irradiation at 10 J/cm(2) produced a down
      regulation of cyclooxygenase 2 (Cox-2) immunoexpression on day 7 post-injury.
      Moreover, Cox-2 immunoexpression was decreased in both treated groups on day 14.
      CONCLUSIONS: Laser therapy at both fluencies stimulated muscle repair through the
      formation of new muscle fiber, increase in collagen synthesis, and down
      regulation of Cox-2 expression.

PMID- 25372002
TI  - Low back pain in adolescent and associated factors: A cross sectional study with
      schoolchildren.
AB  - OBJECTIVE: To determine the prevalence of low back pain nonspecific and
      associated factors in schoolchildren. METHOD: This cross-sectional study
      investigated 343 adolescents, aged between 12 and 15 years, of both sexes of
      public schools. The questionnaire included questions regarding sociodemographic
      characteristics, type of school transportation, body mass index and low back
      pain. The outcome was defined as discomfort localized below the costal margin and
      above the inferior gluteal folds in the last 12 months. RESULTS: The prevalence
      of low back pain in the last year was 57% (n=195) among participants, with no
      significant difference between the sexes (OR 1.13, 95% CI 0.93 to 1.37).
      Advancing age and body mass index were associated with the presence of low back
      pain in the bivariate analysis. The remaining seated at school in usual days was
      considered one of the main activities that trigger symptoms that lasted up to
      seven days for the majority (80%) of adolescents. CONCLUSIONS: The high
      prevalence of low back pain presented, indicating that it is a common condition
      among these adolescents. There was no difference between the sexes, but had
      influence of age and body mass index. Our results point to the need for the
      development epidemiological studies of low back pain among children and
      adolescents.

PMID- 25372003
TI  - Predictive equations for respiratory muscle strength according to international
      and Brazilian guidelines.
AB  - BACKGROUND: The maximum static respiratory pressures, namely the maximum
      inspiratory pressure (MIP) and maximum expiratory pressure (MEP), reflect the
      strength of the respiratory muscles. These measures are simple, non-invasive, and
      have established diagnostic and prognostic value. This study is the first to
      examine the maximum respiratory pressures within the Brazilian population
      according to the recommendations proposed by the American Thoracic Society and
      European Respiratory Society (ATS/ERS) and the Brazilian Thoracic Association
      (SBPT). OBJECTIVE: To establish reference equations, mean values, and lower
      limits of normality for MIP and MEP for each age group and sex, as recommended by
      the ATS/ERS and SBPT. METHOD: We recruited 134 Brazilians living in Belo
      Horizonte, MG, Brazil, aged 20-89 years, with a normal pulmonary function test
      and a body mass index within the normal range. We used a digital manometer that
      operationalized the variable maximum average pressure (MIP/MEP). At least five
      tests were performed for both MIP and MEP to take into account a possible
      learning effect. RESULTS: We evaluated 74 women and 60 men. The equations were as
      follows: MIP=63.27-0.55 (age)+17.96 (gender)+0.58 (weight), r(2) of 34% and MEP= 
      61.41+2.29 (age) - 0.03(age(2))+33.72 (gender)+1.40 (waist), r(2) of 49%.
      CONCLUSION: In clinical practice, these equations could be used to calculate the
      predicted values of MIP and MEP for the Brazilian population.

PMID- 25372004
TI  - Effect of a single session of transcranial direct-current stimulation on balance
      and spatiotemporal gait variables in children with cerebral palsy: A randomized
      sham-controlled study.
AB  - BACKGROUND: Transcranial direct-current stimulation (tDCS) has been widely
      studied with the aim of enhancing local synaptic efficacy and modulating the
      electrical activity of the cortex in patients with neurological disorders.
      OBJECTIVE: The purpose of the present study was to determine the effect of a
      single session of tDCS regarding immediate changes in spatiotemporal gait and
      oscillations of the center of pressure (30 seconds) in children with cerebral
      palsy (CP). METHOD: A randomized controlled trial with a blinded evaluator was
      conducted involving 20 children with CP between six and ten years of age. Gait
      and balance were evaluated three times: Evaluation 1 (before the stimulation),
      Evaluation 2 (immediately after stimulation), and Evaluation 3 (20 minutes after
      the stimulation). The protocol consisted of a 20-minute session of tDCS applied
      to the primary motor cortex at an intensity of 1 mA. The participants were
      randomly allocated to two groups: experimental group - anodal stimulation of the
      primary motor cortex; and control group - placebo transcranial stimulation.
      RESULTS: Significant reductions were found in the experimental group regarding
      oscillations during standing in the anteroposterior and mediolateral directions
      with eyes open and eyes closed in comparison with the control group (p<0.05). In
      the intra-group analysis, the experimental group exhibited significant
      improvements in gait velocity, cadence, and oscillation in the center of pressure
      during standing (p<0.05). No significant differences were found in the control
      group among the different evaluations. CONCLUSION: A single session of tDCS
      applied to the primary motor cortex promotes positive changes in static balance
      and gait velocity in children with cerebral palsy.

PMID- 25372005
TI  - Relationship among vaginal palpation, vaginal squeeze pressure, electromyographic
      and ultrasonographic variables of female pelvic floor muscles.
AB  - BACKGROUND: The proper evaluation of the pelvic floor muscles (PFM) is essential
      for choosing the correct treatment. Currently, there is no gold standard for the
      assessment of female PFM function. OBJECTIVE: To determine the correlation
      between vaginal palpation, vaginal squeeze pressure, and electromyographic and
      ultrasonographic variables of the female PFM. METHOD: This cross-sectional study
      evaluated 80 women between 18 and 35 years of age who were nulliparous and had no
      pelvic floor dysfunction. PFM function was assessed based on digital palpation,
      vaginal squeeze pressure, electromyographic activity, bilateral diameter of the
      bulbocavernosus muscles and the amount of bladder neck movement during voluntary
      PFM contraction using transperineal bi-dimensional ultrasound. The Pearson
      correlation was used for statistical analysis (p<0.05). RESULTS: There was a
      strong positive correlation between PFM function and PFM contraction pressure
      (0.90). In addition, there was a moderate positive correlation between these two
      variables and PFM electromyographic activity (0.59 and 0.63, respectively) and
      movement of the bladder neck in relation to the pubic symphysis (0.51 and 0.60,
      respectively). CONCLUSIONS: This study showed that there was a correlation
      between vaginal palpation, vaginal squeeze pressure, and electromyographic and
      ultrasonographic variables of the PFM in nulliparous women. The strong
      correlation between digital palpation and PFM contraction pressure indicated that
      perineometry could easily be replaced by PFM digital palpation in the absence of
      equipment.

PMID- 25372006
TI  - Influences of hand dominance on the maintenance of benefits after home-based
      modified constraint-induced movement therapy in individuals with stroke.
AB  - OBJECTIVE: To investigate the influence of hand dominance on the maintenance of
      gains after home-based modified constraint-induced movement therapy (mCIMT).
      METHOD: Aprevious randomized controlled trial was conducted to examine the
      addition of trunk restraint to the mCIMT. Twenty-two chronic stroke survivors
      with mild to moderate motor impairments received individual home-based mCIMT with
      or without trunk restraints, five times per week, three hours daily over two
      weeks. In this study, the participants were separated into dominant group, which
      had their paretic upper limb as dominant before the stroke (n=8), and non
      dominant group (n=14) for analyses. The ability to perform unimanual tasks was
      measured by the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL),
      whereas the capacity to perform bimanual tasks was measured using the Bilateral
      Activity Assessment Scale (BAAS). RESULTS: Analysis revealed significant positive
      effects on the MAL amount of use and quality of the movement scales, as well as
      on the BAAS scores after intervention, with no differences between groups. Both
      groups maintained the bimanual improvements during follow-ups (BAAS-seconds 0.1,
      95% CI -10.0 to 10.0), however only the dominant group maintained the unilateral
      improvements (MAL-amount of use: 1.5, 95% CI 0.7 to 2.3; MAL-quality: 1.3, 95% CI
      0.5 to 2.1). CONCLUSIONS: Upper limb dominance did not interfere with the
      acquisition of upper limb skills after mCIMT. However, the participants whose
      paretic upper limb was dominant demonstrated better abilities to maintain the
      unilateral gains. The bilateral improvements were maintained, regardless of upper
      limb dominance.

PMID- 25372007
TI  - Influence of dual task and frailty on gait parameters of older community-dwelling
      individuals.
AB  - BACKGROUND: Gait parameters such as gait speed (GS) are important indicators of
      functional capacity. Frailty Syndrome is closely related to GS and is also
      capable of predicting adverse outcomes. The cognitive demand of gait control is
      usually explored with dual-task (DT) methodology. OBJECTIVE: To investigate the
      effect of DT and frailty on the spatio-temporal parameters of gait in older
      people and identify which variables relate to GS. METHOD: The presence of frailty
      was verified by Fried's Frailty Criteria. Cognitive function was evaluated with
      the Mini-Mental State Exam (MMSE) and gait parameters were analyzed through the
      GAITRite((r)) system in the single-task and DT conditions. The Kolmogorov
      Smirnov, ANOVA, and Pearson's Correlation tests were administered. RESULTS: The
      participants were assigned to the groups frail (FG), pre-frail (PFG), and non
      frail (NFG). During the DT, the three groups showed a decrease in GS, cadence,
      and stride length and an increase in stride time (p<0.001). The reduction in the
      GS of the FG during the DT showed a positive correlation with the MMSE scores
      (r=730; p=0.001) and with grip strength (r=681; p=0.001). CONCLUSIONS: Gait
      parameters are more affected by the DT, especially in the frail older subjects.
      The reduction in GS in the FG is associated with lower grip strength and lower
      scores in the MMSE. The GS was able to discriminate the older adults in the three
      levels of frailty, being an important measure of the functional capacity in this
      population.

PMID- 25372008
TI  - The Brazilian version of STarT Back Screening Tool - translation, cross-cultural
      adaptation and reliability.
AB  - BACKGROUND: Psychosocial factors are not routinely identified in physical therapy
      assessments, although they can influence the prognosis of patients with low back
      pain. The "STarT Back Screening Tool" (SBST) questionnaire aids in screening such
      patients for poor prognosis in the primary care setting and classifies them as
      high, medium, or low risk based on physical and psychosocial factors. OBJECTIVES:
      This study sought to translate and cross-culturally adapt the SBST to the
      Brazilian Portuguese language and test the reliability of the Brazilian version.
      METHOD: The first stage of the study consisted of the translation, synthesis, and
      back-translation of the original version of the STSB, including revision by the
      Translation Group, pretest of the translated version, and assessment by an expert
      panel. The pre-final Brazilian version was applied to 2 samples comprising 52
      patients with low back pain; these patients were of both genders and older than
      18 years of age. To assess the instrument's reliability, an additional sample
      comprising 50 patients was subjected to 2 interviews, and the results were
      assessed using the quadratic weighted kappa value. The instrument's internal
      consistency was assessed using Cronbach's alpha (n=105), and the standard error
      of measurement was also calculated (n=50). RESULTS: Translation and back
      translation attained consensus, and only item 6 required changes; the
      reformulated version was applied to an additional sample comprising 52
      individuals who did not report any doubts related to this item. The reliability
      of the SBST-Brazil was 0.79 (95% confidence interval: 0.63-0.95), the internal
      consistency was 0.74 for the total score and 0.72 for the psychosocial subscale,
      and the standard error of measurement was 1.9%. CONCLUSION: The translated and
      cross-culturally adapted SBST-Brazil proved to be reliable for screening patients
      according to their risk of poor prognosis and the presence of psychosocial
      factors.

PMID- 25372010
TI  - Health Care Indicators.
AB  - THIS REGULAR FEATURE OF THE JOURNAL INCLUDES A DISCUSSION OF EACH OF THE
      FOLLOWING FOUR TOPICS: community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25372011
TI  - Multidrug and extensive drug resistance in Pseudomonas aeruginosa clinical
      isolates from a Portuguese central hospital: 10-year survey.
AB  - Multidrug-resistant (MDR) Pseudomonas aeruginosa isolates are increasing
      worldwide and greatly limit therapeutic options, particularly when considering
      extensively drug-resistant (XDR) or pandrug-resistant isolates. The resistance
      profile of P. aeruginosa isolates from a Portuguese central hospital was surveyed
      during 10 years (n=3,778). About 39.9% were classified as MDR and 2.9% as XDR.
      Statistical analysis (Mann-Whitney test and regression modeling) revealed a
      decrease in total MDR rates over time but an increase in XDR rates. This suggests
      a tendency for higher proportions of XDR isolates in the future, which is of
      great concern. Isolates of nosocomial origin presented similar results to total
      population but, when analyzing them according to the different wards of origin,
      it was still observed a trend of increase in MDR rates in some wards,
      particularly pneumology, neurology, and neurosurgery. Similar analysis
      considering the nosocomial specimen source revealed a negative trend of evolution
      in MDR rates of respiratory origin and a positive trend over time in XDR rates of
      isolates collected from urine. Regarding the association of antibiotic resistance
      to MDR and XDR profiles, it was observed a negative relation over time between
      imipenem resistance and MDR and gentamicin resistance and XDR, suggesting that
      resistance to these antibiotics may predict the absence of MDR or XDR in P.
      aeruginosa isolates, respectively. Similar studies in other European hospitals
      should be performed to give further information to physicians, important for
      their empirical antibiotherapy regimens. 

PMID- 25372009
TI  - Early and current physical activity: relationship with intima-media thickness and
      metabolic variables in adulthood.
AB  - BACKGROUND: It is unclear whether early physical activity has a greater influence
      on intima-media thickness and metabolic variables than current physical activity.
      OBJECTIVE: To analyze the relationship between current and early physical
      activity, metabolic variables, and intima-media thickness measures in adults.
      METHOD: The sample was composed of 55 healthy subjects of both sexes (33 men and
      22 women). Total body fat and trunk fat were estimated by dual-energy X-ray
      absorptiometry. Carotid and femoral intima-media thickness were measured using a
      Doppler ultrasound device. A 12-hour fasting blood sample collection was taken
      (fasting glucose and lipid profile). Early physical activity was assessed through
      face-to-face interview, and the current physical activity was assessed by
      pedometer (Digi-Walker Yamax, SW200), which was used for a period of seven days.
      RESULTS: Current physical activity was negatively related to total cholesterol
      (rho=-0.31), while early physical activity was negatively related to
      triglycerides (rho=-0.42), total cholesterol (rho=-0.28), very low density
      lipoprotein (rho=-0.44), and carotid intima-media thickness (rho=-0.50). In the
      multivariate model, subjects engaged in sports activities during early life had
      lower values of very low density lipoprotein (b=-8.74 [b95%CI=-16.1; -1.47]) and
      carotid intima-media thickness (b=-0.17 [95%CI: -0.28; -0.05]). CONCLUSION: Early
      95%CI physical activity has a significant influence on carotid intima-media
      thickness, regardless of the current physical activity.

PMID- 25372012
TI  - Comparison of the active-site design of molybdenum oxo-transfer enzymes by
      quantum mechanical calculations.
AB  - There are three families of mononuclear molybdenum enzymes that catalyze oxygen
      atom transfer (OAT) reactions, named after a typical example from each family,
      viz., dimethyl sulfoxide reductase (DMSOR), sulfite oxidase (SO), and xanthine
      oxidase (XO). These families differ in the construction of their active sites,
      with two molybdopterin groups in the DMSOR family, two oxy groups in the SO
      family, and a sulfido group in the XO family. We have employed density functional
      theory calculations on cluster models of the active sites to understand the
      selection of molybdenum ligands in the three enzyme families. Our calculations
      show that the DMSOR active site has a much stronger oxidative power than the
      other two sites, owing to the extra molybdopterin ligand. However, the active
      sites do not seem to have been constructed to make the OAT reaction as exergonic
      as possible, but instead to keep the reaction free energy close to zero (to avoid
      excessive loss of energy), thereby making the reoxidation (SO and XO) or
      rereduction of the active sites (DMSOR) after the OAT reaction facile. We also
      show that active-site models of the three enzyme families can all catalyze the
      reduction of DMSO and that the DMSOR model does not give the lowest activation
      barrier. Likewise, all three models can catalyze the oxidation of sulfite,
      provided that the Coulombic repulsion between the substrate and the enzyme model
      can be overcome, but for this harder reaction, the SO model gives the lowest
      activation barrier, although the differences are not large. However, only the XO
      model can catalyze the oxidation of xanthine, owing to its sulfido ligand. 

PMID- 25372013
TI  - Experience vs experiments with the purse-string closure: unexpected results.

PMID- 25372014
TI  - A novel variation of GDF3 in Chinese Han children with a broad phenotypic
      spectrum of non-syndromic CHDs.
AB  - BACKGROUND: The GDF3 gene plays a fundamental role in embryonic morphogenesis.
      Recent studies have indicated that GDF3 plays a previously unrecognised role in
      cardiovascular system development. Non-syndromic CHDs might be a clinically
      isolated manifestation of GDF3 mutations. The purpose of the present study was to
      identify potential pathological mutations in the GDF3 gene in Chinese children
      with non-syndromic CHDs, and to gain insight into the aetiology of non-syndromic
      CHDs. METHODS: A total of 200 non-syndromic CHDs patients and 202 normal control
      patients were sampled. There were two exons of the human GDF3 gene amplified
      using polymerase chain reaction. The polymerase chain reaction products were
      purified and directly sequenced. RESULTS: One missense mutation (c.C635T,
      p.Ser212 Leu, phenotype: isolated muscular ventricular septal defect) was found
      that has not been reported previously. CONCLUSIONS: To the best of our knowledge,
      this is the first study to investigate the role of the GDF3 gene in non-syndromic
      CHDs. Our results expand the spectrum of mutations associated with CHDs and first
      suggest the potentially disease-related GDF3 gene variant in the pathogenesis of
      CHDs.

PMID- 25372015
TI  - Overview.
AB  - This issue features child and adolescent health care, focusing especially on the
      effectiveness of the 1989 Omnibus Budget Reconciliation Act (OBRA 89), which
      expanded health benefits to more children and pregnant women in Medicaid. Also
      featured: the effectiveness of some managed health care plans for Medicaid
      eligible children, and injury hospitalizations in California in 1992. Some of the
      material is particularly relevant to the Children's Health Insurance Program
      (CHIP), which is the current effort to insure the Nation's working poor.

PMID- 25372017
TI  - A Copula Approach to Joint Modeling of Longitudinal Measurements and Survival
      Times Using Monte Carlo Expectation-Maximization with Application to AIDS
      Studies.
AB  - Joint modeling of longitudinal measurements and time to event data is often
      performed by fitting a shared parameter model. Another method for joint modeling
      that may be used is a marginal model. As a marginal model, we use a Gaussian
      model for joint modeling of longitudinal measurements and time to event data. We
      consider a regression model for longitudinal data modeling and a Weibull
      proportional hazard model for event time data modeling. A Gaussian copula is used
      to consider the association between these two models. A Monte Carlo expectation
      maximization approach is used for parameter estimation. Some simulation studies
      are conducted in order to illustrate the proposed method. Also, the proposed
      method is used for analyzing a clinical trial dataset. 

PMID- 25372016
TI  - gammaS-crystallin proteins from the Antarctic nototheniid toothfish: a model
      system for investigating differential resistance to chemical and thermal
      denaturation.
AB  - The gammaS1- and gammaS2-crystallins, structural eye lens proteins from the
      Antarctic toothfish (Dissostichus mawsoni), are homologues of the human lens
      protein gammaS-crystallin. Although gammaS1 has the higher thermal stability of
      the two, it is more susceptible to chemical denaturation by urea. The lower
      thermodynamic stability of both toothfish crystallins relative to human gammaS
      crystallin is consistent with the current picture of how proteins from organisms
      endemic to perennially cold environments have achieved low-temperature
      functionality via greater structural flexibility. In some respects, the sequences
      of gammaS1- and gammaS2-crystallin are typical of psychrophilic proteins;
      however, their amino acid compositions also reflect their selection for a high
      refractive index increment. Like their counterparts in the human lens and those
      of mesophilic fish, both toothfish crystallins are relatively enriched in
      aromatic residues and methionine and exiguous in aliphatic residues. The
      sometimes contradictory requirements of selection for cold tolerance and high
      refractive index make the toothfish crystallins an excellent model system for
      further investigation of the biophysical properties of structural proteins. 

PMID- 25372018
TI  - The first report of a Pelecaniformes defensin cluster: characterization of beta
      defensin genes in the crested ibis based on BAC libraries.
AB  - Defensins play a key role in the innate immunity of various organisms. Detailed
      genomic studies of the defensin cluster have only been reported in a limited
      number of birds. Herein, we present the first characterization of defensins in a
      Pelecaniformes species, the crested ibis (Nipponia nippon), which is one of the
      most endangered birds in the world. We constructed bacterial artificial
      chromosome libraries, including a 4D-PCR library and a reverse-4D library, which
      provide at least 40 equivalents of this rare bird's genome. A cluster including
      14 beta-defensin loci within 129 kb was assigned to chromosome 3 by FISH, and one
      gene duplication of AvBD1 was found. The ibis defensin genes are characterized by
      multiform gene organization ranging from two to four exons through extensive exon
      fusion. Splicing signal variations and alternative splice variants were also
      found. Comparative analysis of four bird species identified one common and
      multiple species-specific duplications, which might be associated with high GC
      content. Evolutionary analysis revealed birth-and-death mode and purifying
      selection for avian defensin evolution, resulting in different defensin gene
      numbers among bird species and functional conservation within orthologous genes,
      respectively. Additionally, we propose various directions for further research on
      genetic conservation in the crested ibis.

PMID- 25372019
TI  - Predicted and actual end-of-treatment occlusion produced with aligner therapy.
AB  - OBJECTIVE: To compare three-dimensional (3D) ClinCheckTM models with the
      subjects' actual 3D posttreatment models using the American Board of Orthodontics
      Objective Grading System (OGS). MATERIALS AND METHODS: This prospective, within
      subject study included 27 consecutive cases treated with aligner therapy. The
      posttreatment plaster models taken immediately after treatment were scanned and
      converted to stereolithography (STL) files; the ClinCheck models were also
      converted to STL format. MeshLab software was used to measure the seven
      components of the OGS, including alignment, marginal ridges, buccolingual
      inclinations, occlusal contacts, occlusal relationships, overjet and
      interproximal contacts. An overall OGS deduction score was also calculated.
      RESULTS: Compared with the posttreatment models, the ClinCheck models showed
      significantly (P  =  .016) fewer overall OGS point deductions (24 vs 15). These
      overall differences were due to significantly (P < .05) more deductions among the
      posttreatment models than the ClinCheck models for alignment (4.0 vs 1.0
      deductions), buccolingual inclinations (4.0 vs 3.0 deductions), occlusal contacts
      (3.0 vs 2.0 deductions), and occlusal relations (4.0 vs 2.0 deductions).
      CONCLUSION: The ClinCheck models do not accurately reflect the patients' final
      occlusion, as measured by the OGS, at the end of active treatment.

PMID- 25372021
TI  - Quantitative DNA interstrand cross-link formation by coumarin and thymine:
      structure determination, sequence effect, and fluorescence detection.
AB  - The coumarin analogues have been widely utilized in medicine, biology,
      biochemistry, and material sciences. Here, we report a detailed study on the
      reactivity of coumarins toward DNA. A series of coumarin analogues were
      synthesized and incorporated into oligodeoxynucleotides. A photoinduced [2 + 2]
      cycloaddition occurs between the coumarin moiety and the thymidine upon 350 nm
      irradiation forming both syn- and anti-cyclobutane adducts (17 and 18), which are
      photoreversible by 254/350 nm irradiation in DNA. Quantitative DNA interstrand
      cross-link (ICL) formation was observed with the coumarin moieties containing a
      flexible two-carbon or longer chain. DNA cross-linking by coumarins shows a
      kinetic preference when flanked by an A:T base pair as opposed to a G:C pair. An
      efficient photoinduced electron transfer between coumarin and dG slows down ICL
      formation. ICL formation quenches the fluorescence of coumarin, which, for the
      first time, enables fast, easy, and real-time monitoring of DNA cross-linking and
      photoreversibility via fluorescence spectroscopy. It can be used to detect the
      transversion mutation between pyrimidines and purines. Overall, this work
      provides new insights into the biochemical properties and possible toxicity of
      coumarins. A quantitative, fluorescence-detectable, and photoswitchable DNA cross
      linking reaction of the coumarin moieties can potentially serve as mechanistic
      probes and tools for bioresearch without disrupting native biological
      environment. 

PMID- 25372022
TI  - Resumption of intercourse after childbirth in southwest Nigeria.
AB  - OBJECTIVE: To determine the history of resumption of intercourse after childbirth
      and associated contraceptive practices among women in the southwest region of
      Nigeria. METHODS: A cohort of 181 women with live births was followed up for 6
      months after delivery. Enquiry about the time of first intercourse after
      childbirth, associated dyspareunia, use of contraception, etc was made during the
      postnatal clinic visits and/or by telephone contact. RESULTS: Fifty (27.6%) had
      coitus within six weeks of childbirth, it increased to 115 (63.3%) at three
      months and 127 (70.2%) by six months post-delivery. Prevalence of dyspareunia was
      36.2%. Eighty three (65.4%) of sexually active women practiced contraception
      which was predominantly use of male condom and withdrawal method. Co-habitation
      with husband (adjusted OR: 6.30; 95% CI: 2.56-17.01; p = 0.001) and mode of
      delivery (adjusted OR: 2.45; 95% CI: 1.30-4.73; p = 0.006) were strong predictors
      of commencement of sexual intercourse within six months postpartum. Significantly
      fewer women who had Caesarean section resumed coitus within six months when
      compared with those who had vaginal deliveries (59.2% versus 78.4%). Perineal
      injury did not predict resumption of coitus or experience of dyspareunia.
      CONCLUSION: In contrast to the norm, more women in southwest Nigeria are resuming
      coitus soon after childbirth. It is imperative to scale up counselling on
      postpartum sexuality and contraception within the maternal health services in
      this region.

PMID- 25372024
TI  - Health Care Indicators: Hospital, Employment and Price Indicators for the Health
      Care Industry: Third Quarter 1997.
AB  - This regular feature of the journal includes a discussion of recent trends in
      health care spending, employment, and prices. The statistics presented in this
      article are valuable in their own right and for understanding the relationship
      between the health care sector and the overall economy. In addition, they allow
      us to anticipate the direction and magnitude of health care cost changes prior to
      the availability of more comprehensive data.

PMID- 25372020
TI  - Mer590, a novel monoclonal antibody targeting MER receptor tyrosine kinase,
      decreases colony formation and increases chemosensitivity in non-small cell lung
      cancer.
AB  - The successes of targeted therapeutics against EGFR and ALK in non-small cell
      lung cancer (NSCLC) have demonstrated the substantial survival gains made
      possible by precision therapy. However, the majority of patients do not have
      tumors with genetic alterations responsive to these therapies, and therefore
      identification of new targets is needed. Our laboratory previously identified MER
      receptor tyrosine kinase as one such potential target. We now report our findings
      targeting MER with a clinically translatable agent--Mer590, a monoclonal antibody
      specific for MER. Mer590 rapidly and robustly reduced surface and total MER
      levels in multiple cell lines. Treatment reduced surface MER levels by 87%, and
      this effect was maximal within four hours. Total MER levels were also
      dramatically reduced, and this persisted for at least seven days.
      Mechanistically, MER down-regulation was mediated by receptor internalization and
      degradation, leading to inhibition of downstream signaling through STAT6, AKT,
      and ERK1/2. Functionally, this resulted in increased apoptosis, increased
      chemosensitivity to carboplatin, and decreased colony formation. In addition to
      carboplatin, Mer590 interacted cooperatively with shRNA-mediated MER inhibition
      to augment apoptosis. These data demonstrate that MER inhibition can be achieved
      with a monoclonal antibody in NSCLC. Optimization toward a clinically available
      anti-MER antibody is warranted.

PMID- 25372025
TI  - Mental Health Issues.
AB  - The following overview discusses and compares the findings and implications of
      the articles in this issue of the Health Care Financing Review that deal with
      mental health topics-particularly children's mental health- in the Medicaid
      context. It also briefly describes articles concerning prospective payments for
      psychiatric patients under Medicare.

PMID- 25372026
TI  - MCBS Highlights: Dually Eligible Medicare Beneficiaries.

PMID- 25372029
TI  - Malaria, schistosomiasis and soil transmitted helminth burden and their
      correlation with anemia in children attending primary schools in Kinshasa,
      Democratic Republic of Congo.
AB  - BACKGROUND: Anaemia reduces cognitive potential in school children, retards their
      growth and predisposes them to other diseases. As there is a paucity of data on
      the current burden of P. falciparum, S. mansoni and soil transmitted helminths
      (STH) infections and their correlation with schoolchildren's anemia in the
      Democratic Republic of Congo (DRC), we collect these data. METHODS: This study
      reports baseline data collected from a randomized controlled trial investigating
      the impact of IPT with SP and SP-PQ on anemia and malaria morbidity in Congolese
      schoolchildren (Trial registration: NCT01722539; PACTR201211000449323). S.
      mansoni and STH infections were assessed using kato-katz technique. Malaria
      infection and hemoglobin concentration were assessed using Blood smear and
      Hemocontrol device, respectively. RESULTS: A total of 616 primary schoolchildren
      from 4 to 13 years old were enrolled in the study. The prevalence of Plasmodium
      spp. infection was 18.5% (95%CI:15.6-21.9). Amongst those infected, 24 (21%), 40
      (35.1%), 40 (35.1%), 10 (8.8%), had light, moderate, heavy, very high malaria
      parasite density, respectively. Above 9 years of age (p = 0.02), male and history
      of fever (p = 0.04) were both associated with malaria infection. The overall
      prevalence of S. mansoni infection was 6.4% (95%CI:4.4-9.1). Girls were
      associated with S. mansoni infection (p = 0.04). T. trichiura was the most
      prevalent STH infection (26.3%), followed by A. lumbricoides (20.1%). Co
      infection with malaria-S. mansoni and malaria-STH was, respectively, 1.5%
      (CI95%:0.7-3.3) and 6.4% (CI95% 4.4-9.1). The prevalence of anemia was found to
      be 41.6% (95%CI:37.7-45.6) and anemia was strongly related with Plasmodium ssp
      infection (aOR:4.1; CI95%:2.6-6.5;p<0.001) and S. mansoni infection
      (aOR:3.3;CI95%:1.4-7.8;p<0.01). CONCLUSION: Malaria and S. mansoni infection were
      strongly associated with high prevalence of anemia in schoolchildren. Therefore,
      specific school-based interventions, such as intermittent preventive treatment or
      prophylaxis, LLITN distribution, anthelminthic mass treatment and micronutrient
      supplementation are needed to improve school children's health.

PMID- 25372030
TI  - Equipment-free incubation of recombinase polymerase amplification reactions using
      body heat.
AB  - The development of isothermal amplification platforms for nucleic acid detection
      has the potential to increase access to molecular diagnostics in low resource
      settings; however, simple, low-cost methods for heating samples are required to
      perform reactions. In this study, we demonstrated that human body heat may be
      harnessed to incubate recombinase polymerase amplification (RPA) reactions for
      isothermal amplification of HIV-1 DNA. After measuring the temperature of mock
      reactions at 4 body locations, the axilla was chosen as the ideal site for
      comfortable, convenient incubation. Using commonly available materials, 3 methods
      for securing RPA reactions to the body were characterized. Finally, RPA reactions
      were incubated using body heat while control RPA reactions were incubated in a
      heat block. At room temperature, all reactions with 10 copies of HIV-1 DNA and
      90% of reactions with 100 copies of HIV-1 DNA tested positive when incubated with
      body heat. In a cold room with an ambient temperature of 10 degrees Celsius, all
      reactions containing 10 copies or 100 copies of HIV-1 DNA tested positive when
      incubated with body heat. These results suggest that human body heat may provide
      an extremely low-cost solution for incubating RPA reactions in low resource
      settings. 

PMID- 25372031
TI  - Computational and functional characterization of Angiogenin mutations, and
      correlation with amyotrophic lateral sclerosis.
AB  - The Angiogenin (ANG) gene is frequently mutated in patients suffering from the
      neurodegenerative disease--amyotrophic lateral sclerosis (ALS). Most of the ALS
      causing mutations in Angiogenin affect either its ribonucleolytic or nuclear
      translocation activity. Here we report the functional characterization of two
      previously uncharacterized missense mutations in Angiogenin--D22G and L35P. We
      predict the nature of loss-of-function(s) in these mutants through our previously
      established Molecular Dynamics (MD) simulation extended to 100 ns, and show that
      the predictions are entirely validated through biochemical studies with wild-type
      and mutated proteins. Based on our studies, we provide a biological explanation
      for the loss-of-function of D22G-Angiogenin leading to ALS, and suggest that the
      L35P-Angiogenin mutation would probably cause ALS symptoms in individuals
      harboring this mutation. Our study thus highlights the strength of MD simulation
      based predictions, and suggests that this method can be used for correlating
      mutations in Angiogenin or other effector proteins with ALS symptoms.

PMID- 25372033
TI  - ICU-Onset Clostridium difficile infection in a university hospital in China: a
      prospective cohort study.
AB  - A prospective study was conducted to investigate the incidence, clinical profiles
      and outcome of ICU-onset CDI in a 50-bed medical ICU at a university hospital in
      China. Stools were collected from patients who developed ICU-onset diarrhea and
      was screened for tcdA (toxin A gene) and tcdB (toxin B gene) by PCR. CDI cases
      were compared with the ICU-onset non-CDI diarrhea cases for demographics,
      comorbidities, potential risk factors, major laboratory findings and outcomes.
      Stool samples from CDI cases were subjected to C. difficile culture and C.
      difficile isolates were screened for tcdA, tcdB and the binary toxin genes (cdtA
      and cdtB) using multiplex PCR. Strain typing of toxigenic C. difficile isolates
      was performed using multilocus sequence typing. There were 1,277 patients in the
      ICU during the study period and 124 (9.7%) developed ICU-onset diarrhea, of which
      31 patients had CDI. The incidence of ICU-onset CDI was 25.2 cases per 10,000 ICU
      days. ICU-onset CDI cases had similar features with ICU-onset non-CDI diarrhea
      cases including the use of proton pump inhibitors and antibacterial agents. The
      crude mortality rate of ICU-onset CDI was 22.6%, but the attributable mortality
      rate of ICU-onset CDI was only 3.2% here. Toxigenic C. difficile isolates were
      recovered from 28 out of the 31 patients with CDI. cdtA and cdtB were found in
      two strains. Seventeen STs including 11 new STs were identified. All of the 11
      new STs were single-locus variants of known STs and the 17 STs identified here
      could be clustered into 3 clades. The incidence of ICU-onset CDI here is similar
      to those in Europe and North America, suggesting that CDI is likely to be a
      common problem in China. Toxigenic C. difficile here belonged to a variety of
      STs, which may represent a significant clonal expansion rather than the true
      clonal diversity. 

PMID- 25372032
TI  - Rnd3 regulates lung cancer cell proliferation through notch signaling.
AB  - Rnd3/RhoE is a small Rho GTPase involved in the regulation of different cell
      behaviors. Dysregulation of Rnd3 has been linked to tumorigenesis and metastasis.
      Lung cancers are the leading cause of cancer-related death in the West and around
      the world. The expression of Rnd3 and its ectopic role in non-small cell lung
      cancer (NSCLC) remain to be explored. Here, we reported that Rnd3 was down
      regulated in three NSCLC cell lines: H358, H520 and A549. The down-regulation of
      Rnd3 led to hyper-activation of Rho Kinase and Notch signaling. The
      reintroduction of Rnd3 or selective inhibition of Notch signaling, but not Rho
      Kinase signaling, blocked the proliferation of H358 and H520 cells.
      Mechanistically, Notch intracellular domain (NICD) protein abundance in H358
      cells was regulated by Rnd3-mediated NICD proteasome degradation. Rnd3 regulated
      H358 and H520 cell proliferation through a Notch1/NICD/Hes1 signaling axis
      independent of Rho Kinase. 

PMID- 25372034
TI  - Transcriptome sequencing and de novo analysis of cytoplasmic male sterility and
      maintenance in JA-CMS cotton.
AB  - Cytoplasmic male sterility (CMS) is the failure to produce functional pollen,
      which is inherited maternally. And it is known that anther development is
      modulated through complicated interactions between nuclear and mitochondrial
      genes in sporophytic and gametophytic tissues. However, an unbiased transcriptome
      sequencing analysis of CMS in cotton is currently lacking in the literature. This
      study compared differentially expressed (DE) genes of floral buds at the
      sporogenous cells stage (SS) and microsporocyte stage (MS) (the two most
      important stages for pollen abortion in JA-CMS) between JA-CMS and its fertile
      maintainer line JB cotton plants, using the Illumina HiSeq 2000 sequencing
      platform. A total of 709 (1.8%) DE genes including 293 up-regulated and 416 down
      regulated genes were identified in JA-CMS line comparing with its maintainer line
      at the SS stage, and 644 (1.6%) DE genes with 263 up-regulated and 381 down
      regulated genes were detected at the MS stage. By comparing the two stages in the
      same material, there were 8 up-regulated and 9 down-regulated DE genes in JA-CMS
      line and 29 up-regulated and 9 down-regulated DE genes in JB maintainer line at
      the MS stage. Quantitative RT-PCR was used to validate 7 randomly selected DE
      genes. Bioinformatics analysis revealed that genes involved in reduction
      oxidation reactions and alpha-linolenic acid metabolism were down-regulated,
      while genes pertaining to photosynthesis and flavonoid biosynthesis were up
      regulated in JA-CMS floral buds compared with their JB counterparts at the SS
      and/or MS stages. All these four biological processes play important roles in
      reactive oxygen species (ROS) homeostasis, which may be an important factor
      contributing to the sterile trait of JA-CMS. Further experiments are warranted to
      elucidate molecular mechanisms of these genes that lead to CMS. 

PMID- 25372035
TI  - Integration of UAV photogrammetry and SPH modelling of fluids to study runoff on
      real terrains.
AB  - Roads can experience runoff problems due to the intense rain discharge associated
      to severe storms. Two advanced tools are combined to analyse the interaction of
      complex water flows with real terrains. UAV (Unmanned Aerial Vehicle)
      photogrammetry is employed to obtain accurate topographic information on small
      areas, typically on the order of a few hectares. The Smoothed Particle
      Hydrodynamics (SPH) technique is applied by means of the DualSPHysics model to
      compute the trajectory of the water flow during extreme rain events. The use of
      engineering solutions to palliate flood events is also analysed. The study case
      simulates how the collected water can flow into a close road and how
      precautionary measures can be effective to drain water under extreme conditions.
      The amount of water arriving at the road is calculated under different protection
      scenarios and the efficiency of a ditch is observed to decrease when
      sedimentation reduces its depth. 

PMID- 25372036
TI  - Measuring what latent fingerprint examiners consider sufficient information for
      individualization determinations.
AB  - Latent print examiners use their expertise to determine whether the information
      present in a comparison of two fingerprints (or palmprints) is sufficient to
      conclude that the prints were from the same source (individualization). When
      fingerprint evidence is presented in court, it is the examiner's determination-
      not an objective metric--that is presented. This study was designed to ascertain
      the factors that explain examiners' determinations of sufficiency for
      individualization. Volunteer latent print examiners (n = 170) were each assigned
      22 pairs of latent and exemplar prints for examination, and annotated features,
      correspondence of features, and clarity. The 320 image pairs were selected
      specifically to control clarity and quantity of features. The predominant factor
      differentiating annotations associated with individualization and inconclusive
      determinations is the count of corresponding minutiae; other factors such as
      clarity provided minimal additional discriminative value. Examiners' counts of
      corresponding minutiae were strongly associated with their own determinations;
      however, due to substantial variation of both annotations and determinations
      among examiners, one examiner's annotation and determination on a given
      comparison is a relatively weak predictor of whether another examiner would
      individualize. The extensive variability in annotations also means that we must
      treat any individual examiner's minutia counts as interpretations of the
      (unknowable) information content of the prints: saying "the prints had N
      corresponding minutiae marked" is not the same as "the prints had N corresponding
      minutiae." More consistency in annotations, which could be achieved through
      standardization and training, should lead to process improvements and provide
      greater transparency in casework.

PMID- 25372037
TI  - Pathogen reduction in human plasma using an ultrashort pulsed laser.
AB  - Pathogen reduction is a viable approach to ensure the continued safety of the
      blood supply against emerging pathogens. However, the currently licensed pathogen
      reduction techniques are ineffective against non-enveloped viruses such as
      hepatitis A virus, and they introduce chemicals with concerns of side effects
      which prevent their widespread use. In this report, we demonstrate the
      inactivation of both enveloped and non-enveloped viruses in human plasma using a
      novel chemical-free method, a visible ultrashort pulsed laser. We found that
      laser treatment resulted in 2-log, 1-log, and 3-log reductions in human
      immunodeficiency virus, hepatitis A virus, and murine cytomegalovirus in human
      plasma, respectively. Laser-treated plasma showed >=70% retention for most
      coagulation factors tested. Furthermore, laser treatment did not alter the
      structure of a model coagulation factor, fibrinogen. Ultrashort pulsed lasers are
      a promising new method for chemical-free, broad-spectrum pathogen reduction in
      human plasma. 

PMID- 25372038
TI  - Force control is related to low-frequency oscillations in force and surface EMG.
AB  - Force variability during constant force tasks is directly related to oscillations
      below 0.5 Hz in force. However, it is unknown whether such oscillations exist in
      muscle activity. The purpose of this paper, therefore, was to determine whether
      oscillations below 0.5 Hz in force are evident in the activation of muscle.
      Fourteen young adults (21.07 +/- 2.76 years, 7 women) performed constant
      isometric force tasks at 5% and 30% MVC by abducting the left index finger. We
      recorded the force output from the index finger and surface EMG from the first
      dorsal interosseous (FDI) muscle and quantified the following outcomes: 1)
      variability of force using the SD of force; 2) power spectrum of force below 2
      Hz; 3) EMG bursts; 4) power spectrum of EMG bursts below 2 Hz; and 5) power
      spectrum of the interference EMG from 10-300 Hz. The SD of force increased
      significantly from 5 to 30% MVC and this increase was significantly related to
      the increase in force oscillations below 0.5 Hz (R(2) = 0.82). For both force
      levels, the power spectrum for force and EMG burst was similar and contained most
      of the power from 0-0.5 Hz. Force and EMG burst oscillations below 0.5 Hz were
      highly coherent (coherence = 0.68). The increase in force oscillations below 0.5
      Hz from 5 to 30% MVC was related to an increase in EMG burst oscillations below
      0.5 Hz (R(2) = 0.51). Finally, there was a strong association between the
      increase in EMG burst oscillations below 0.5 Hz and the interference EMG from 35
      60 Hz (R(2) = 0.95). In conclusion, this finding demonstrates that bursting of
      the EMG signal contains low-frequency oscillations below 0.5 Hz, which are
      associated with oscillations in force below 0.5 Hz.

PMID- 25372039
TI  - Individual variation in cone photoreceptor density in house sparrows:
      implications for between-individual differences in visual resolution and
      chromatic contrast.
AB  - Between-individual variation has been documented in a wide variety of taxa,
      especially for behavioral characteristics; however, intra-population variation in
      sensory systems has not received similar attention in wild animals. We measured a
      key trait of the visual system, the density of retinal cone photoreceptors, in a
      wild population of house sparrows (Passer domesticus). We tested whether
      individuals differed from each other in cone densities given within-individual
      variation across the retina and across eyes. We further tested whether the
      existing variation could lead to individual differences in two aspects of
      perception: visual resolution and chromatic contrast. We found consistent between
      individual variation in the densities of all five types of avian cones, involved
      in chromatic and achromatic vision. Using perceptual modeling, we found that this
      degree of variation translated into significant between-individual differences in
      visual resolution and the chromatic contrast of a plumage signal that has been
      associated with mate choice and agonistic interactions. However, there was no
      evidence for a relationship between individual visual resolution and chromatic
      contrast. The implication is that some birds may have the sensory potential to
      perform "better" in certain visual tasks, but not necessarily in both resolution
      and contrast simultaneously. Overall, our findings (a) highlight the need to
      consider multiple individuals when characterizing sensory traits of a species,
      and (b) provide some mechanistic basis for between-individual variation in
      different behaviors (i.e., animal personalities) and for testing the predictions
      of several widely accepted hypotheses (e.g., honest signaling). 

PMID- 25372041
TI  - The use of biologically related model (Eclipse) for the intensity-modulated
      radiation therapy planning of nasopharyngeal carcinomas.
AB  - PURPOSE: Intensity-modulated radiation therapy (IMRT) is the most common
      treatment technique for nasopharyngeal carcinoma (NPC). Physical quantities such
      as dose/dose-volume parameters are used conventionally for IMRT optimization. The
      use of biological related models has been proposed and can be a new trend. This
      work was to assess the performance of the biologically based IMRT optimization
      model installed in a popular commercial treatment planning system (Eclipse) as
      compared to its dose/dose volume optimization model when employed in the clinical
      environment for NPC cases. METHODS: Ten patients of early stage NPC and ten of
      advanced stage NPC were selected for this study. IMRT plans optimized using
      biological related approach (BBTP) were compared to their corresponding plans
      optimized using the dose/dose volume based approach (DVTP). Plan evaluation was
      performed using both biological indices and physical dose indices such as tumor
      control probability (TCP), normal tissue complication probability (NTCP), target
      coverage, conformity, dose homogeneity and doses to organs at risk. The
      comparison results of the more complex advanced stage cases were reported
      separately from those of the simpler early stage cases. RESULTS: The target
      coverage and conformity were comparable between the two approaches, with BBTP
      plans producing more hot spots. For the primary targets, BBTP plans produced
      comparable TCP for the early stage cases and higher TCP for the advanced stage
      cases. BBTP plans reduced the volume of parotid glands receiving doses of above
      40 Gy compared to DVTP plans. The NTCP of parotid glands produced by BBTP were
      8.0 +/- 5.8 and 7.9 +/- 8.7 for early and advanced stage cases, respectively,
      while those of DVTP were 21.3 +/- 8.3 and 24.4 +/- 12.8, respectively. There were
      no significant differences in the NTCP values between the two approaches for the
      serial organs. CONCLUSIONS: Our results showed that the BBTP approach could be a
      potential alternative approach to the DVTP approach for NPC.

PMID- 25372040
TI  - Feasibility of beta-sheet breaker peptide-H102 treatment for Alzheimer's disease
      based on beta-amyloid hypothesis.
AB  - beta-amyloid hypothesis is the predominant hypothesis in the study of
      pathogenesis of Alzheimer's disease. This hypothesis claims that aggregation and
      neurotoxic effects of amyloid beta (Abeta) is the common pathway in a variety of
      etiological factors for Alzheimer's disease. Abeta peptide derives from amyloid
      precursor protein (APP). beta-sheet breaker peptides can directly prevent and
      reverse protein misfolding and aggregation in conformational disorders. Based on
      the stereochemical structure of Abeta1-42 and aggregation character, we had
      designed a series of beta-sheet breaker peptides in our previous work and
      screened out a 10-residue peptide beta-sheet breaker peptide, H102. We evaluated
      the effects of H102 on expression of P-tau, several associated proteins,
      inflammatory factors and apoptosis factors, and examined the cognitive ability of
      APP transgenic mice by behavioral test. This study aims to validate the beta
      amyloid hypothesis and provide an experimental evidence for the feasibility of
      H102 treatment for Alzheimer's disease. 

PMID- 25372045
TI  - Revisiting the conundrum of trehalose stabilization.
AB  - Protein aggregation and loss of protein's biological functionality are
      manifestations of protein instability. Cosolvents, in particular trehalose, are
      widely accepted antidotes against such destabilization. Although numerous
      theories have been promulgated in the literature with regard to its mechanism of
      stabilization, the present scenario is still elusive in view of the discrepancies
      existing in them. To this end, we have revisited the conundrum and attempted to
      rationalize the mechanism by conducting thorough investigation of the effect of
      trehalose on the native, partially unfolded and denatured states of protein
      "Lysozyme" by means of molecular dynamic (MD) simulations under different
      temperature and concentration regimes. Two-dimensional contour plots along with
      principal component analysis suggest that trehalose molecules offer on-pathway
      stabilization unaltering the principal direction of protein's motion, although it
      slows down protein dynamics so that the protein gets trapped in the homogeneous
      ensemble of conformations closer to the native state. Free energy landscape
      reveals higher population of native compared to intermediate and denatured
      states. Delphi results and calculation of the preferential interaction parameter
      demonstrate that this relative stabilization of the native state can be ascribed
      to be the consequence of favourable interactions of trehalose with side chains of
      certain loci on the protein surface encompassing polar flexible residues.
      Stability of protein results from the observed difference in binding affinity of
      trehalose for native and denatured states of protein. Our findings are at
      variance with the common conception of relative destabilization of the denatured
      state. Rather, we provide evidence for relative stabilization of the native
      state. This stabilization is due to interplay of protein-trehalose, water
      trehalose, water-water, protein-water and trehalose-trehalose interactions. 

PMID- 25372044
TI  - Willingness to participate in HIV therapeutic vaccine trials among HIV-infected
      patients on ART in China.
AB  - BACKGROUND: More and more HIV therapeutic vaccines will enter clinical trials;
      however, little is known about the willingness to participate (WTP) in HIV
      therapeutic vaccine trials among HIV-positive individuals. OBJECTIVE: To
      investigate the WTP in HIV therapeutic vaccine trials among Chinese HIV-infected
      patients. METHODS: We conducted a cross-sectional survey on HIV-positive
      inpatients and outpatients at Shanghai Public Health Center. A total of 447
      participants were recruited into this study. Following an introduction with
      general information on HIV therapeutic vaccine and its potential effectiveness
      and side effects, each participant completed a questionnaire in a self
      administered form. The questionnaires covered demographics, high-risk behaviors,
      clinical characteristics and willingness to participate in HIV therapeutic
      vaccine trial. RESULTS: The overall willingness to participate in HIV therapeutic
      vaccine trials was 91.5%. Interestingly, multivariate logistic regression
      analyses demonstrated that the willingness was higher for those sexually infected
      by HIV (odds ratio [OR]: 4.36; 95% confidence interval [CI]: 1.53-12.41),
      diagnosed as HIV-1 infection for greater than 5 years (OR: 7.12, 95% CI: 1.83
      27.76), and with the presence of infectious complications (OR: 2.75; 95% CI: 1.02
      7.45). The primary reason for participation was to delay or reduce antiretroviral
      treatment (ART) and to avoid ART side effects (76.6%), and then followed by
      delaying disease progression (74.9%), increasing immune response to suppress
      opportunistic infections (57.7%) and preventing the development of drug
      resistance (37.1%). Reasons for unwillingness to participate mainly included
      concern for safety (37.0%), lack of knowledge on therapeutic vaccine (33.3%), and
      satisfaction with ART effectiveness (22.2%). CONCLUSIONS: The WTP in HIV
      therapeutic vaccine trials was high among HIV-infected Chinese patients. HIV+
      subjects who acquired infection through sexual contact and who were diagnosed for
      more than 5 years may represent a good candidate population for enrollment in
      therapeutic vaccine trials.

PMID- 25372046
TI  - Fluorescence polarization immunoassays for monitoring nucleoside triphosphate
      diphosphohydrolase (NTPDase) activity.
AB  - The following members of the ecto-nucleoside triphosphate diphosphohydrolase
      family, NTPDase1 (CD39), NTPDase-2, -3, and -8, play an important role in
      purinergic signal transduction by regulating extracellular nucleotide levels.
      Potent and selective NTPDase inhibitors are required as pharmacological tools and
      have potential as novel drugs, e.g. for anti-cancer and anti-bacterial therapy.
      We have developed fast and sensitive NTPDase fluorescence polarization (FP)
      immunoassays using the natural substrates (ATP or ADP). During the NTPDase1
      catalyzed reaction, the substrate is dephosphorylated to ADP which is further
      dephosphorylated yielding AMP as the final product (by NTPDase1). NTPDase3 and -8
      yield AMP and ADP, while NTPDase2 results mainly in the formation of ADP. Direct
      quantification of the respective product, AMP or ADP, is achieved by displacement
      of an appropriate fluorescent tracer nucleotide from a specific antibody leading
      to a change in fluorescence polarization. The assays are highly sensitive and can
      be performed with low substrate concentrations (20 MUM ATP or 10 MUM ADP) below
      the KM values of NTPDases, which simplifies the identification of novel
      competitive inhibitors. Optimized antibody and enzyme concentrations allow the
      reproducible detection of 2 MUM ADP and 1 MUM AMP (at 10% substrate conversion).
      Validation of the assays yielded excellent Z'-factors greater than 0.70 for all
      investigated NTPDase subtypes indicating high robustness of the analytical
      method. Furthermore, we tested a standard inhibitor and performed a first
      exemplary screening campaign with a library consisting of >400 compounds (Z'
      factor: 0.87, hit rate 0.5%). Thereby we demonstrated the suitability of the FP
      assay for IC50 value determination and high-throughput screening in a 384-well
      format. The new FP assays were shown to be superior to current standard assays. 

PMID- 25372043
TI  - Impact of co-infections and BCG immunisation on immune responses among household
      contacts of tuberculosis patients in a Ugandan cohort.
AB  - BACKGROUND: Tuberculosis incidence in resource poor countries remains high. We
      hypothesized that immune modulating co-infections such as helminths, malaria, and
      HIV increase susceptibility to latent tuberculosis infection (LTBI), thereby
      contributing to maintaining the tuberculosis epidemic. METHODS: Adults with
      sputum-positive tuberculosis (index cases) and their eligible household contacts
      (HHCs) were recruited to a cohort study between May 2011 and January 2012. HHCs
      were investigated for helminths, malaria, and HIV at enrolment. HHCs were tested
      using the QuantiFERON-TB Gold In-Tube (QFN) assay at enrolment and six months
      later. Overnight whole blood culture supernatants from baseline QFN assays were
      analyzed for cytokine responses using an 11-plex Luminex assay. Associations
      between outcomes (LTBI or cytokine responses) and exposures (co-infections and
      other risk factors) were examined using multivariable logistic and linear
      regression models. RESULTS: We enrolled 101 index cases and 291 HHCs. Among HHCs,
      baseline prevalence of helminths was 9% (25/291), malaria 16% (47/291), HIV 6%
      (16/291), and LTBI 65% (179/277). Adjusting for other risk factors and household
      clustering, there was no association between LTBI and any co-infection at
      baseline or at six months: adjusted odds ratio (95% confidence interval (CI); p
      value) at baseline for any helminth, 1.01 (0.39-2.66; 0.96); hookworm, 2.81 (0.56
      14.14; 0.20); malaria, 1.06 (0.48-2.35; 0.87); HIV, 0.74 (0.22-2.47; 0.63). HHCs
      with LTBI had elevated cytokine responses to tuberculosis antigens but co
      infections had little effect on cytokine responses. Exploring other risk factors,
      Th1 cytokines among LTBI-positive HHCs with BCG scars were greatly reduced
      compared to those without scars: (adjusted geometric mean ratio) IFNgamma 0.20
      (0.09-0.42), <0.0001; IL-2 0.34 (0.20-0.59), <0.0001; and TNFalpha 0.36 (0.16
      0.79), 0.01. CONCLUSIONS: We found no evidence that co-infections increase the
      risk of LTBI, or influence the cytokine response profile among those with LTBI.
      Prior BCG exposure may reduce Th1 cytokine responses in LTBI.

PMID- 25372047
TI  - Overview, History, and Objectives of Performance Measurement.
AB  - This article provides an overview of health care performance measurement,
      including a chronological history of the major developments in the performance
      measurement field. It is not intended to be all-encompassing in its descriptions
      of events and organizations but, rather, its purpose is to provide a broad
      historical context for describing health care performance measurement activities
      of the past 50 years. The article also highlights the key constituents driving
      performance measurement (government payers, private sector regulators, business
      coalitions, health care providers, and health care consumers), how they have
      influenced what is measured (the content of performance measurement), and why.
      The article concludes by establishing the commonalities among constituents and
      forecasts what the foreseeable future may hold regarding performance measurement.

PMID- 25372049
TI  - Provider and Insurer Perspective.
AB  - This executive summary of Senator Durenberger's remarks was prepared by Julie
      Snyder of the University of Texas LBJ School of Public Affairs. The remarks were
      given in the context of a panel presentation moderated by Senator Durenberger,
      entitled "Provider and Insurer Perspective."

PMID- 25372048
TI  - Utilization management as a cost-containment strategy.
AB  - Utilization management (UM) is now an integral part of most public and private
      health plans. Hospital review, until recently the primary focus of UM, is
      associated with a reduction in bed days and rate of hospital cost increases.
      These reductions appear to have had limited impact on aggregate health care costs
      because of increases in unmanaged services. In the future, with electronic
      connectivity between payers and providers and the use of clinical guidelines and
      computer-based decision-support systems, the need for prospective case-level
      reviews will be reduced. With these changes, UM programs are likely to become
      more acceptable to providers and patients.

PMID- 25372050
TI  - Silk fibroin-keratin based 3D scaffolds as a dermal substitute for skin tissue
      engineering.
AB  - Development of highly vascular dermal tissue-engineered skin substitutes with
      appropriate mechanical properties and cellular cues is in need for significant
      advancement in the field of dermal reconstruction. Limitations have been imposed
      on natural biomaterials despite their superb biocompatibility hence, studies in
      biomaterial blending have been ongoing. Herein, we investigated blends of silk
      fibroin and human hair-derived keratin as wound-healing substrates that promote
      enhanced fibroblast cell adhesion and proliferation. Three-dimensional (3D)
      blended scaffolds were fabricated by freeze-drying, and their physico-chemical,
      mechanical and degradable properties were extensively characterized.
      Cytocompatibility tests observing cell adhesion and cell proliferation have shown
      significant enhancements in blended scaffolds. Also, its structural composition
      with high porosity (>85%) and interconnected pores in the range of 100-120
      microns further confirms the superiority of the complex compared to its
      counterparts. FTIR studies identified the enhanced stability within its structure
      and were followed-up with sequential experiments to demonstrate improved thermal,
      degradation, and mechanical properties. Furthermore, immunohistochemical staining
      revealed greater expression of collagen type I in the cultured cells, indicating
      functional fibroblast proliferation and, hence, the exciting potential of this
      construct for dermal applications. Taken together, this study demonstrates the
      promising attributes from blended biomaterials and specifically present silk
      fibroin and human hair keratin blended scaffolds as a promising dermal substitute
      for skin tissue engineering. 

PMID- 25372051
TI  - PIP4kgamma is a substrate for mTORC1 that maintains basal mTORC1 signaling during
      starvation.
AB  - Phosphatidylinositol-5-phosphate 4-kinases (PIP4ks) are a family of lipid kinases
      that specifically use phosphatidylinositol 5-monophosphate (PI-5-P) as a
      substrate to synthesize phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2].
      Suppression of PIP4k function in Drosophila results in smaller cells and reduced
      target of rapamycin complex 1 (TORC1) signaling. We showed that the gamma isoform
      of PIP4k stimulated signaling through mammalian TORC1 (mTORC1). Knockdown of
      PIP4kgamma reduced cell mass in cells in which mTORC1 is constitutively activated
      by Tsc2 deficiency. In Tsc2 null cells, mTORC1 activation was partially
      independent of amino acids or glucose and glutamine. PIP4kgamma knockdown
      inhibited the nutrient-independent activation of mTORC1 in Tsc2 knockdown cells
      and reduced basal mTORC1 signaling in wild-type cells. PIP4kgamma was
      phosphorylated by mTORC1 and associated with the complex. Phosphorylated
      PIP4kgamma was enriched in light microsomal vesicles, whereas the
      unphosphorylated form was enriched in heavy microsomal vesicles associated with
      the Golgi. Furthermore, basal mTORC1 signaling was enhanced by overexpression of
      unphosphorylated wild-type PIP4kgamma or a phosphorylation-defective mutant and
      decreased by overexpression of a phosphorylation-mimetic mutant. Together, these
      results demonstrate that PIP4kgamma and mTORC1 interact in a self-regulated
      feedback loop to maintain low and tightly regulated mTORC1 activation during
      starvation.

PMID- 25372052
TI  - Protein folding creates structure-based, noncontiguous consensus phosphorylation
      motifs recognized by kinases.
AB  - Linear consensus motifs are short contiguous sequences of residues within a
      protein that can form recognition modules for protein interaction or catalytic
      modification. Protein kinase specificity and the matching of kinases to
      substrates have been mostly defined by phosphorylation sites that occur in linear
      consensus motifs. However, phosphorylation can also occur within sequences that
      do not match known linear consensus motifs recognized by kinases and within
      flexible loops. We report the identification of Thr(253) in alpha-tubulin as a
      site that is phosphorylated by protein kinase C betaI (PKCbetaI). Thr(253) is not
      part of a linear PKC consensus motif. Instead, Thr(253) occurs within a region on
      the surface of alpha-tubulin that resembles a PKC phosphorylation site consensus
      motif formed by basic residues in different parts of the protein, which come
      together in the folded protein to form the recognition motif for PKCbetaI.
      Mutations of these basic residues decreased substrate phosphorylation, confirming
      the presence of this "structurally formed" consensus motif and its importance for
      the protein kinase-substrate interaction. Analysis of previously reported protein
      kinase A (PKA) and PKC substrates identified sites within structurally formed
      consensus motifs in many substrates of these two kinase families. Thus, the
      concept of consensus phosphorylation site motif needs to be expanded to include
      sites within these structurally formed consensus motifs. 

PMID- 25372054
TI  - Evolution of Quality Review Programs for Medicare: Quality Assurance to Quality
      Improvement.
AB  - This article outlines the development, successes, and future directions of the
      Medicare Peer Review Organization (PRO) program. As established by the Tax Equity
      and Fiscal Responsibility Act of 1982, the purpose of the PRO program is to
      promote the quality, medical necessity, and appropriateness of services
      reimbursed through Medicare. We describe the evolution of the PRO program from a
      retrospective quality review approach, focused on individual events, to a
      proactive, quality improvement approach. Priorities for future development are
      described, including the identification of additional clinical areas for
      attention, improvements in program infrastructure, and broadening the scope of
      projects to new provider settings.

PMID- 25372055
TI  - Ametantrone-based compounds as potential regulators of Tau pre-mRNA alternative
      splicing.
AB  - Tau pre-mRNA contains a stem-loop structure involved in the regulation of the
      alternative splicing of tau protein. We describe here a new family of Tau RNA
      ligands selected by dynamic combinatorial chemistry based on the combination of
      ametantrone with small RNA-binding molecules. The most promising compound results
      from derivatization of one of the side chains of the anthraquinone ring with the
      small aminoglycoside neamine through a short spacer. This compound binds the RNA
      target with a high affinity in a preferred binding site, in which the
      heteroaromatic moiety intercalates in the bulged region of the stem-loop and its
      side chains and neamine interact with the major groove of the RNA. Importantly,
      binding of this compound to mutated RNA sequences involved in the onset of some
      tauopathies such as FTDP-17 restores their thermodynamic stability to a similar
      or even higher levels than that of the wild-type sequence, thereby revealing its
      potential as a modulator of Tau pre-mRNA splicing. 

PMID- 25372053
TI  - MicroRNAs meet calcium: joint venture in ER proteostasis.
AB  - The endoplasmic reticulum (ER) is a cellular compartment that has a key function
      in protein translation and folding. Maintaining its integrity is of fundamental
      importance for organism's physiology and viability. The dynamic regulation of
      intraluminal ER Ca(2+) concentration directly influences the activity of ER
      resident chaperones and stress response pathways that balance protein load and
      folding capacity. We review the emerging evidence that microRNAs play important
      roles in adjusting these processes to frequently changing intracellular and
      environmental conditions to modify ER Ca(2+) handling and storage and maintain ER
      homeostasis. 

PMID- 25372056
TI  - Health Reform, Year Seven: Observations About Medicaid Managed Care.
AB  - Over the last 7 years, State and Federal policymakers have reformed State medical
      assistance programs and, in the process, have grappled with goals of both
      containing program costs and expanding health insurance coverage to the
      uninsured. Currently, nearly one-quarter of all States have implemented health
      care reform demonstrations, and this article summarizes trends seen since health
      care reform began in the 1990s. As well as noting the accomplishments of health
      care reform through the use of Medicaid managed care, the article speculates,
      based on recent evidence, about new directions health care reform may take in the
      future.

PMID- 25372057
TI  - Health Care Indicators.
AB  - THIS REGULAR FEATURE OF THE JOURNAL INCLUDES A DISCUSSION OF EACH OF THE
      FOLLOWING FOUR TOPICS: community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25372058
TI  - Impact of training in autism for primary care providers: a pilot study.
AB  - OBJECTIVE: To evaluate the impact of a training program on autism spectrum
      disorder (ASD) identification offered to Brazilian health professionals. METHODS:
      Twenty-two primary care providers participated in five 3-hour weekly training
      sessions. RESULTS: The trained providers significantly improved their ASD
      knowledge after training in comparison with pre-training (mean score, 6.73 vs.
      9.18, p < 0.01). Clinical practice also changed: 4 months after the training
      program, the providers had referred six times as many suspected cases of ASD to a
      specialized mental health service in comparison with the previous 4 months.
      CONCLUSION: This pilot training model seems a promising, feasible, and
      inexpensive way to improve early identification of ASD in the primary care
      system.

PMID- 25372060
TI  - [Citationrates and impact factors of german journals in the psychosocial field].

PMID- 25372059
TI  - Are the binary typology models of alcoholism valid in polydrug abusers?
AB  - OBJECTIVE: To evaluate the dichotomy of type I/II and type A/B alcoholism
      typologies in opiate-dependent patients with a comorbid alcohol dependence
      problem (ODP-AP). METHODS: The validity assessment process comprised the
      information regarding the history of alcohol use (internal validity), cognitive
      behavioral variables regarding substance use (external validity), and indicators
      of treatment during 6-month follow-up (predictive validity). RESULTS: ODP-AP
      subjects classified as type II/B presented an early and much more severe drinking
      problem and a worse clinical prognosis when considering opiate treatment
      variables as compared with ODP-AP subjects defined as type I/A. Furthermore, type
      II/B patients endorse more general positive beliefs and expectancies related to
      the effect of alcohol and tend to drink heavily across several intra- and
      interpersonal situations as compared with type I/A patients. CONCLUSIONS: These
      findings confirm two different forms of alcohol dependence, recognized as a low
      severity/vulnerability subgroup and a high-severity/vulnerability subgroup, in an
      opiate-dependent population with a lifetime diagnosis of alcohol dependence.

PMID- 25372061
TI  - [The identity of medical psychology: a historical quest].
AB  - The starting point of this study is the current uncertainty in German-speaking
      medical psychology about its actual and very own natural area of expertise. The
      current study ventures to advance the hypothesis that part of this uncertainty is
      due to the fact that during the scientific area in its history (approx. 1850
      1960) medical psychology abandoned its historical core competence as it emerged
      and developed during the age of enlightenment (end of 17(th)-18(th) centuries).
      To make this change clear, different examples of the 2 opposing
      conceptualisations of medical psychology are discussed, of course in a selected
      and maybe even provocative way. The change in concept also led to the fact that
      the interrelationships with and differentiation from its neighbouring disciplines
      are not clear and sharp either, since at times 2 or more disciplines declare
      themselves competent for one and the same thing. This is exemplified on the
      manifold overlappings with clinical psychology. Given the lack of resources now
      and in the future, this lack of a clear definition of competence might lead to
      continued uncertainty as well as to conflicts over distribution. On the other
      hand though, the look into the history of the subject reveals that at all times
      it has been a matter of individual approach or attitude as to what was regarded
      as core area of interest and competence of medical psychology and how far it
      overlapped with neighbouring disciplines. From the point of view of the history
      of psychiatry and on the basis of carefully selected historic material, this
      paper presents the core of 2 different concepts of medical psychology to
      elaborate this hypothesis. 

PMID- 25372062
TI  - [Qualitative health services research].

PMID- 25372063
TI  - Novel micro-rings of molybdenum disulfide (MoS2).
AB  - Recently, molybdenum disulfide (MoS(2)) has become a popular material due to its
      unique electrical and chemical properties, and its use as a potential substitute
      for graphene. Herein, we report a new two-step method by utilizing thermal
      evaporation-sulfurization to synthesize MoS(2) which possesses an innovative
      micro-ring structure. The average statistical values of the height, width and
      external diameter were 69 nm, 0.3 MUm and 5.0 MUm, respectively. Then the
      mechanism for the growth of such MoS(2) micro-rings was proposed. A device based
      on the MoS(2) micro-ring was prepared by electron beam lithography, and its
      electrical transport properties were determined at different temperatures.

PMID- 25372064
TI  - High-Risk Pools for Uninsurable Individuals: Recent Growth, Future Prospects.
AB  - High-risk pools are State programs that were recently brought under Federal
      review by the Health Insurance Portability and Accountability Act of 1996
      (HIPAA). For a subsidized, yet above-standard premium, they provide coverage to
      individuals lacking access to private health insurance, typically due to pre
      existing conditions. Reducing high-risk pool premiums in all States to the level
      prevailing in the most generous States (at an annual cost of about $105 million)
      could lead to a modest but significant increase in enrollment, relative to the
      uninsurable population. In addition, non-premium changes, for example to benefits
      and marketing, could also have substantial effects on enrollment.

PMID- 25372065
TI  - Overview.

PMID- 25372067
TI  - Cyclosporine in the management of poststreptococcal pustulosis.

PMID- 25372068
TI  - Impact of Medicaid Expansion on Early Prenatal Care and Health Outcomes.
AB  - To assess the impact of Medicaid expansion for pregnant women in South Carolina
      and California, the authors compared change in rates of timely prenatal care,
      adverse infant and maternal health outcomes, and use of cesarean section for
      groups of pregnant women who were either uninsured or covered by Medicaid, versus
      women with private coverage. The results showed small and/or inconsistent
      changes. Provision of coverage may be the first logical step in improving health
      care for the uninsured, but outcomes may rely more on outreach, coordination of
      care, and non-medical interventions than on provision of insurance coverage per
      se.

PMID- 25372069
TI  - The use of chemical actinometry for the evaluation of the light absorption
      efficiency in scattering photopolymerizable miniemulsions.
AB  - Oil-in-water miniemulsions containing a mixture of monomers as the dispersed
      organic phase have been shown recently to be promising media for the development
      of photoinitiated polymerization processes. Albeit a crucial factor for a
      successful application, the efficiency of light absorption by the photoinitiator
      in these highly scattering systems is difficult to evaluate. In this work, a well
      characterized water insoluble chemical actinometer (DFIS) replaced the oil
      soluble photoinitiator, and was used as a probe and a model for UV light
      absorption in miniemulsions of variable droplet sizes and organic phase
      compositions (i.e. at different levels of scattered light). In the first step,
      the photon flux absorbed by the actinometer was determined in model miniemulsions
      based on an inert solvent (ethyl acetate), at a low oil phase content (3.0-6.0
      wt%). For these low to moderately scattering systems, the photon flux absorbed by
      the actinometer in the miniemulsions was comparable to that in a homogeneous
      solution of ethyl acetate. In the second step, the absorbed photon flux was
      investigated in photopolymerizable miniemulsions (a mixture of acrylate monomers
      as oil phase). Surprisingly, in spite of much higher scattering coefficients than
      those found for ethyl acetate based miniemulsions of otherwise the same
      composition, the photon flux absorbed by the actinometer in photopolymerizable
      miniemulsions showed only a small decreasing trend. Such a result may be
      considered favorable for the further development of applications of
      photopolymerizations in miniemulsions. 

PMID- 25372070
TI  - The influence of physical therapy and anti-botulinum toxin antibody on the
      efficacy of botulinum toxin-A injections in children with spastic cerebral palsy.
AB  - OBJECTIVE: To identify factors associated with the efficacy of botulinum toxin-A
      (BoNT-A) injections. METHODS: Thirty-eight children with spastic cerebral palsy
      (CP) received BoNT-A injections into the gastrocnemius. The baseline anti
      botulinum antibodies were checked. The Static dorsiflexion range of motion (ROM),
      Modified Tardieu Scale (MTS) and Physician Rating Scale (PRS) were assessed at
      pre-injection as well as 4- and 12-week post-injection. RESULTS: No samples
      contained anti-botulinum antibodies. Greater baseline MTS dynamic range was
      associated with greater changes in MTS dynamic ranges at 4-week post-injection.
      More frequent physical therapy was associated with greater changes in static
      dorsiflexion ROM at 4-week post-injection and greater changes in PRS at 4- and 12
      week post-injection. CONCLUSION: The improvement in PRS at 12-week post-injection
      was associated with the frequency of physical therapy. Therefore, intensive
      physical therapy programs may be necessary to maintain the beneficial effects of
      BoNT-A injections in children with CP.

PMID- 25372072
TI  - Stem cell therapies for Parkinson's disease: are trials just around the corner?

PMID- 25372071
TI  - A simple and flexible graphical approach for adaptive group-sequential clinical
      trials.
AB  - In this article, we introduce a graphical approach to testing multiple hypotheses
      in group-sequential clinical trials allowing for midterm design modifications. It
      is intended for structured study objectives in adaptive clinical trials and
      extends the graphical group-sequential designs from Maurer and Bretz (Statistics
      in Biopharmaceutical Research 2013; 5: 311-320) to adaptive trial designs. The
      resulting test strategies can be visualized graphically and performed
      iteratively. We illustrate the methodology with two examples from our clinical
      trial practice. First, we consider a three-armed gold-standard trial with the
      option to reallocate patients to either the test drug or the active control
      group, while stopping the recruitment of patients to placebo, after having
      demonstrated superiority of the test drug over placebo at an interim analysis.
      Second, we consider a confirmatory two-stage adaptive design with treatment
      selection at interim. 

PMID- 25372074
TI  - Centre for human development, stem cells & regeneration.
AB  - The Centre for Human Development, Stem Cells and Regeneration (CHDSCR) was
      founded in 2004 as a cross-disciplinary research and translational program within
      the Faculty of Medicine at the University of Southampton. The Centre undertakes
      fundamental research into early development and stem cells together with applied
      translational research for patient benefit. The Centre has vibrant and thriving
      multidisciplinary research programs that harness the translational strength of
      the Faculty together with an innovative Stem Cell PhD program, outstanding
      clinical infrastructure and enterprise to deliver on this vision. 

PMID- 25372075
TI  - Eighth symposium on biologic scaffolds for regenerative medicine.
AB  - The Eighth Symposium on Biologic Scaffolds for Regenerative Medicine was held
      from 24 to 26 April 2014 at the Silverado Resort in Napa, CA, USA. The symposium
      was well attended by a diverse audience of academic scientists, industry members
      and physicians from around the world. The conference showcased the strong
      foundation of both basic and translational research utilizing biologic scaffolds
      in regenerative medicine applications across nearly all tissue systems and
      facilitated vibrant discussions among participants. This article provides an
      overview of the conference by providing a brief synopsis of selected
      presentations, each focused on a unique research and/or clinical investigation
      currently underway. 

PMID- 25372076
TI  - Reimbursement and adoption of advanced therapies: the 5-C framework.

PMID- 25372077
TI  - Stem cell injection in the hindlimb skeletal muscle enhances neurorepair in mice
      with spinal cord injury.
AB  - AIMS: To develop a low-risk, little-invasive stem cell-based method to treat
      acute spinal cord injuries. methods: Adult mice were submitted to an incomplete
      spinal cord injury, and mesenchymal stem cells injected intramuscularly into both
      hindlimbs. Behavior tests and MRI of the spinal cord were periodically performed
      for up to 6 months, along with immunohistochemical analysis. Immunohistochemical
      and PCR analysis of the muscles were used to detect the grafted cells as well as
      the soluble factors released. RESULTS: The stem cell-treated mice presented
      significant improvements in their motor skills 5 months after treatment. Spinal
      cord repair was detected by magnetic resonance and immunohistochemistry. In the
      hindlimb muscles, the stem cells activated muscle and motor neuron repair
      mechanisms, due to the secretion of several neurotrophic factors. CONCLUSION:
      Bone marrow mesenchymal stem cell injection into hindlimb muscles stimulates
      spinal cord repair in acute spinal cord lesions.

PMID- 25372078
TI  - First transplantation of isolated murine follicles in alginate.
AB  - AIM: Our aim is to develop an artificial ovary allowing survival and growth of
      isolated follicles and ovarian cells, to restore fertility in women diagnosed
      with pathologies at high risk of ovarian involvement. MATERIALS & METHODS: For
      this, alginate beads containing isolated preantral follicles and ovarian cells
      were autografted to immunocompetent mice. One week after grafting, the beads were
      invaded by proliferating murine cells (12.1%) and capillaries. RESULTS: The
      recovery rate of follicles per graft ranged from 0% to 35.5%. Of the analyzed
      follicles, 77% were Ki67-positive and 81%, TUNEL-negative. Three antral follicles
      were also identified, evidencing their ability to grow in the matrix. CONCLUSION:
      Our results suggest that an artificial ovary is now conceivable, opening new
      perspectives to restore fertility in women.

PMID- 25372079
TI  - Mesenchymal stem cell therapy for the treatment of amyotrophic lateral sclerosis:
      signals for hope?
AB  - Based on the distinctive cellular, molecular and immunomodulatory traits of
      mesenchymal stem cells (MSC), it has been postulated that these cells may play a
      critical role in regenerative medicine. In addition to the participation of MSC
      in the repair of mesodermal-derived tissues (bone, cartilage), robust data have
      suggested that MSC may also play a reparative role in conditions involving damage
      of cells of ectodermal origin. The above content has been supported by the
      capability of MSC to differentiate into neuron-like cells as well as by a
      competence to generate a 'neuroprotective' environment. In turn, several
      preclinical studies have put forward the concept that MSC therapy may represent
      an option for the treatment of several neurological disorders and injuries,
      including amyotrophic lateral sclerosis. We expect that the above foundations,
      which have inspired this review, may result in the founding of an effective
      and/or palliative therapy for amyotrophic lateral sclerosis. 

PMID- 25372080
TI  - Cell-based therapy approaches: the hope for incurable diseases.
AB  - Cell therapies aim to repair the mechanisms underlying disease initiation and
      progression, achieved through trophic effect or by cell replacement. Multiple
      cell types can be utilized in such therapies, including stem, progenitor or
      primary cells. This review covers the current state of cell therapies designed
      for the prominent disorders, including cardiovascular, neurological (Parkinson's
      disease, amyotrophic lateral sclerosis, stroke, spinal cord injury), autoimmune
      (Type 1 diabetes, multiple sclerosis, Crohn's disease), ophthalmologic, renal,
      liver and skeletal (osteoarthritis) diseases. Various cell therapies have reached
      advanced clinical trial phases with potential marketing approvals in the near
      future, many of which are based on mesenchymal stem cells. Advances in
      pluripotent stem cell research hold great promise for regenerative medicine. The
      information presented in this review is based on the analysis of the cell therapy
      collection detailed in LifeMap Discovery((r)) (LifeMap Sciences Inc., USA) the
      database of embryonic development, stem cell research and regenerative medicine. 

PMID- 25372081
TI  - The current 'state of play' of regenerative medicine in horses: what the horse
      can tell the human.
AB  - The horse is an attractive model for many human age-related degenerative diseases
      of the musculoskeletal system because it is a large animal species that both ages
      and exercises, and develops naturally occurring injuries with many similarities
      to the human counterpart. It therefore represents an ideal species to use as a
      'proving ground' for new therapies, most notably regenerative medicine.
      Regenerative techniques using cell-based therapies for the treatment of equine
      musculoskeletal disease have been in use for over a decade. This review article
      provides a summary overview of the sources, current challenges and problems
      surrounding the use of stem cell and non-cell-based therapy in regenerative
      medicine in horses and is based on presentations from a recent Havemeyer
      symposium on equine regenerative medicine where speakers are selected from
      leading authorities in both equine and human regenerative medicine fields from 10
      different countries. 

PMID- 25372082
TI  - Protein-based materials in load-bearing tissue-engineering applications.
AB  - Proteins such as collagen and elastin are robust molecules that constitute
      nanocomponents in the hierarchically organized ultrastructures of bone and tendon
      as well as in some of the soft tissues that have load-bearing functions. In the
      present paper, the macromolecular structure and function of the proteins are
      reviewed and the potential of mammalian and non-mammalian proteins in the
      engineering of load-bearing tissue substitutes are discussed. Chimeric proteins
      have become an important structural biomaterial source and their potential in
      tissue engineering is highlighted. Processing of proteins challenge investigators
      and in this review rapid prototyping and microfabrication are proposed as methods
      for obtaining precisely defined custom-built tissue engineered structures with
      intrinsic microarchitecture. 

PMID- 25372083
TI  - Financing Health Care: Businesses, Households, and Governments, 1987-2003.
AB  - This article provides estimates of health care expenditures by businesses,
      households, and governments for 1987-2003. Sponsors that finance public and
      private health insurance programs and other payers face increasing challenges as
      health care cost rise. Their capacity to support rising costs was particularly
      strained during the recent economic recession, with the Federal Government's
      burden measured against revenue available for this purpose growing faster than
      for other sponsors.

PMID- 25372084
TI  - Korea's thyroid-cancer "epidemic"--screening and overdiagnosis.

PMID- 25372086
TI  - Sustained remission with etanercept tapering in early rheumatoid arthritis.
AB  - BACKGROUND: We assessed the effects of reduction and withdrawal of treatment in
      patients with rheumatoid arthritis who had a remission while receiving etanercept
      plus-methotrexate therapy. METHODS: Patients with early active disease who had
      not previously received methotrexate or biologic therapy received 50 mg of
      etanercept plus methotrexate weekly for 52 weeks (open-label phase). We then
      randomly assigned patients who had qualifying responses at weeks 39 and 52 to
      receive 25 mg of etanercept plus methotrexate (combination-therapy group),
      methotrexate alone, or placebo for 39 weeks (double-blind phase). Patients who
      had qualifying responses at week 39 of the double-blind phase had all treatment
      withdrawn at that time and were followed to week 65 (treatment-withdrawal phase).
      The primary end point was the proportion of patients with sustained remission in
      the double-blind phase. RESULTS: Of 306 patients enrolled, 193 underwent
      randomization in the double-blind phase; 131 qualified for the treatment
      withdrawal phase. More patients in the combination-therapy group than in the
      methotrexate-alone group or the placebo group met the criterion for the primary
      end point (40 of 63 [63%] vs. 26 of 65 [40%] and 15 of 65 [23%], respectively;
      P=0.009 for combination therapy vs. methotrexate alone; P<0.001 for combination
      therapy vs. placebo). At 65 weeks, 28 patients (44%) who had received combination
      therapy, 19 (29%) who had received methotrexate alone, and 15 (23%) who had
      received placebo were in remission (P=0.10 for combination therapy vs.
      methotrexate alone; P=0.02 for combination therapy vs. placebo; P=0.55 for
      methotrexate alone vs. placebo). No significant between-group differences were
      observed in radiographic progression of disease. Serious adverse events were
      reported in 3 patients (5%) in the combination-therapy group, 2 (3%) in the
      methotrexate-alone group, and 2 (3%) in the placebo group. CONCLUSIONS: In
      patients with early rheumatoid arthritis who had a remission while receiving full
      dose etanercept-plus-methotrexate therapy, continuing combination therapy at a
      reduced dose resulted in better disease control than switching to methotrexate
      alone or placebo, but no significant difference was observed in radiographic
      progression. (Funded by Pfizer; ClinicalTrials.gov number, NCT00913458.).

PMID- 25372085
TI  - Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis.
AB  - BACKGROUND: The combination of cyclophosphamide and glucocorticoids leads to
      remission in most patients with antineutrophil cytoplasm antibody (ANCA)
      associated vasculitides. However, even when patients receive maintenance
      treatment with azathioprine or methotrexate, the relapse rate remains high.
      Rituximab may help to maintain remission. METHODS: Patients with newly diagnosed
      or relapsing granulomatosis with polyangiitis, microscopic polyangiitis, or renal
      limited ANCA-associated vasculitis in complete remission after a cyclophosphamide
      glucocorticoid regimen were randomly assigned to receive either 500 mg of
      rituximab on days 0 and 14 and at months 6, 12, and 18 after study entry or daily
      azathioprine until month 22. The primary end point at month 28 was the rate of
      major relapse (the reappearance of disease activity or worsening, with a
      Birmingham Vasculitis Activity Score >0, and involvement of one or more major
      organs, disease-related life-threatening events, or both). RESULTS: The 115
      enrolled patients (87 with granulomatosis with polyangiitis, 23 with microscopic
      polyangiitis, and 5 with renal-limited ANCA-associated vasculitis) received
      azathioprine (58 patients) or rituximab (57 patients). At month 28, major relapse
      had occurred in 17 patients in the azathioprine group (29%) and in 3 patients in
      the rituximab group (5%) (hazard ratio for relapse, 6.61; 95% confidence
      interval, 1.56 to 27.96; P=0.002). The frequencies of severe adverse events were
      similar in the two groups. Twenty-five patients in each group (P=0.92) had severe
      adverse events; there were 44 events in the azathioprine group and 45 in the
      rituximab group. Eight patients in the azathioprine group and 11 in the rituximab
      group had severe infections, and cancer developed in 2 patients in the
      azathioprine group and 1 in the rituximab group. Two patients in the azathioprine
      group died (1 from sepsis and 1 from pancreatic cancer). CONCLUSIONS: More
      patients with ANCA-associated vasculitides had sustained remission at month 28
      with rituximab than with azathioprine. (Funded by the French Ministry of Health;
      MAINRITSAN ClinicalTrials.gov number, NCT00748644; EudraCT number, 2008-002846
      51.).

PMID- 25372087
TI  - Cost-effectiveness of CT screening in the National Lung Screening Trial.
AB  - BACKGROUND: The National Lung Screening Trial (NLST) showed that screening with
      low-dose computed tomography (CT) as compared with chest radiography reduced lung
      cancer mortality. We examined the cost-effectiveness of screening with low-dose
      CT in the NLST. METHODS: We estimated mean life-years, quality-adjusted life
      years (QALYs), costs per person, and incremental cost-effectiveness ratios
      (ICERs) for three alternative strategies: screening with low-dose CT, screening
      with radiography, and no screening. Estimations of life-years were based on the
      number of observed deaths that occurred during the trial and the projected
      survival of persons who were alive at the end of the trial. Quality adjustments
      were derived from a subgroup of participants who were selected to complete
      quality-of-life surveys. Costs were based on utilization rates and Medicare
      reimbursements. We also performed analyses of subgroups defined according to age,
      sex, smoking history, and risk of lung cancer and performed sensitivity analyses
      based on several assumptions. RESULTS: As compared with no screening, screening
      with low-dose CT cost an additional $1,631 per person (95% confidence interval
      [CI], 1,557 to 1,709) and provided an additional 0.0316 life-years per person
      (95% CI, 0.0154 to 0.0478) and 0.0201 QALYs per person (95% CI, 0.0088 to
      0.0314). The corresponding ICERs were $52,000 per life-year gained (95% CI,
      34,000 to 106,000) and $81,000 per QALY gained (95% CI, 52,000 to 186,000).
      However, the ICERs varied widely in subgroup and sensitivity analyses.
      CONCLUSIONS: We estimated that screening for lung cancer with low-dose CT would
      cost $81,000 per QALY gained, but we also determined that modest changes in our
      assumptions would greatly alter this figure. The determination of whether
      screening outside the trial will be cost-effective will depend on how screening
      is implemented. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov
      number, NCT00047385.).

PMID- 25372089
TI  - Clinical practice. Lung-cancer screening with low-dose computed tomography.

PMID- 25372091
TI  - Images in clinical medicine. Carotid cavernous fistula.

PMID- 25372090
TI  - Integration of acid-base and electrolyte disorders.

PMID- 25372088
TI  - Changes in medical errors after implementation of a handoff program.
AB  - BACKGROUND: Miscommunications are a leading cause of serious medical errors. Data
      from multicenter studies assessing programs designed to improve handoff of
      information about patient care are lacking. METHODS: We conducted a prospective
      intervention study of a resident handoff-improvement program in nine hospitals,
      measuring rates of medical errors, preventable adverse events, and
      miscommunications, as well as resident workflow. The intervention included a
      mnemonic to standardize oral and written handoffs, handoff and communication
      training, a faculty development and observation program, and a sustainability
      campaign. Error rates were measured through active surveillance. Handoffs were
      assessed by means of evaluation of printed handoff documents and audio
      recordings. Workflow was assessed through time-motion observations. The primary
      outcome had two components: medical errors and preventable adverse events.
      RESULTS: In 10,740 patient admissions, the medical-error rate decreased by 23%
      from the preintervention period to the postintervention period (24.5 vs. 18.8 per
      100 admissions, P<0.001), and the rate of preventable adverse events decreased by
      30% (4.7 vs. 3.3 events per 100 admissions, P<0.001). The rate of nonpreventable
      adverse events did not change significantly (3.0 and 2.8 events per 100
      admissions, P=0.79). Site-level analyses showed significant error reductions at
      six of nine sites. Across sites, significant increases were observed in the
      inclusion of all prespecified key elements in written documents and oral
      communication during handoff (nine written and five oral elements; P<0.001 for
      all 14 comparisons). There were no significant changes from the preintervention
      period to the postintervention period in the duration of oral handoffs (2.4 and
      2.5 minutes per patient, respectively; P=0.55) or in resident workflow, including
      patient-family contact and computer time. CONCLUSIONS: Implementation of the
      handoff program was associated with reductions in medical errors and in
      preventable adverse events and with improvements in communication, without a
      negative effect on workflow. (Funded by the Office of the Assistant Secretary for
      Planning and Evaluation, U.S. Department of Health and Human Services, and
      others.).

PMID- 25372092
TI  - Clinical problem-solving. A chilly fever.

PMID- 25372093
TI  - Extending the indications for rituximab in ANCA-associated vasculitis.

PMID- 25372094
TI  - Transfusions for silent cerebral infarcts in sickle cell anemia.

PMID- 25372095
TI  - Transfusions for silent cerebral infarcts in sickle cell anemia.

PMID- 25372096
TI  - A test for Creutzfeldt-Jakob disease using nasal brushings.

PMID- 25372097
TI  - A test for Creutzfeldt-Jakob disease using nasal brushings.

PMID- 25372098
TI  - Effect of hospital pay for performance on mortality in England.

PMID- 25372099
TI  - Single-pill regimens for HIV-1 infection.

PMID- 25372100
TI  - Single-pill regimens for HIV-1 infection.

PMID- 25372101
TI  - Single-pill regimens for HIV-1 infection.

PMID- 25372102
TI  - Single-pill regimens for HIV-1 infection.

PMID- 25372103
TI  - Syndromes of thrombotic microangiopathy.

PMID- 25372104
TI  - Syndromes of thrombotic microangiopathy.

PMID- 25372105
TI  - Syndromes of thrombotic microangiopathy.

PMID- 25372106
TI  - Syndromes of thrombotic microangiopathy.

PMID- 25372107
TI  - Case 25-2014: A man with ulcerative colitis and bloody diarrhea.

PMID- 25372108
TI  - Case 25-2014: A man with ulcerative colitis and bloody diarrhea.

PMID- 25372109
TI  - Catheterization of the urethra in girls.

PMID- 25372110
TI  - Catheterization of the urethra in girls.

PMID- 25372111
TI  - A new multidrug-resistant strain of Neisseria gonorrhoeae in Australia.

PMID- 25372113
TI  - Images in clinical medicine. Ectopia lentis in Marfan's syndrome.

PMID- 25372114
TI  - MCBS Highlights: Home Health, Facility, and Community Populations.

PMID- 25372115
TI  - Convenient preparation of high-quality specimens for annealing experiments in the
      transmission electron microscope.
AB  - A procedure based on focused ion beam milling and in situ lift-out is introduced
      for the preparation of high-quality specimens for in situ annealing experiments
      in the transmission electron microscope. The procedure allows an electron
      transparent lamella to be cleaned directly on a heating chip using a low ion
      energy and back-side milling in order to minimize redeposition and damage. The
      approach is illustrated through the preparation of an Al-Mn-Fe complex metallic
      alloy specimen. 

PMID- 25372116
TI  - The Effect of Culture on Two Information-Processing Speed Tests.
AB  - The Symbol Digit Modalities Test (SDMT) has been proposed to replace the Paced
      Auditory Serial Addition Test-3 (PASAT-3) in the Multiple Sclerosis Functional
      Composite because it has the same validity but easy and shorter administration.
      However, among the two tests, the one that is most affected by culture is still
      unknown. The purpose of this study was to compare the performance of Argentinian
      and North American populations on the SDMT and PASAT-3. The SDMT and PASAT-3 were
      administered to 137 healthy volunteers from Buffalo, NY, and 137 healthy
      participants from Buenos Aires, Argentina. Participants were matched by gender,
      age (+/-2), and education (+/-1). Significant differences were found on the SDMT
      but not on the PASAT-3. Significant and low correlations were found between the
      tests and years of education. The SDMT is more affected by culture than is the
      PASAT-3. Possible interpretations of this result are presented. 

PMID- 25372118
TI  - Functional Analyses of the Diels-Alderase Gene sol5 of Ascochyta rabiei and
      Alternaria solani Indicate that the Solanapyrone Phytotoxins Are Not Required for
      Pathogenicity.
AB  - Ascochyta rabiei and Alternaria solani, the causal agents of Ascochyta blight of
      chickpea (Cicer arietinum) and early blight of potato (Solanum tuberosum),
      respectively, produce a set of phytotoxic compounds including solanapyrones A, B,
      and C. Although both the phytotoxicity of solanapyrones and their universal
      production among field isolates have been documented, the role of solanapyrones
      in pathogenicity is not well understood. Here, we report the functional
      characterization of the sol5 gene, which encodes a Diels-Alderase that catalyzes
      the final step of solanapyrone biosynthesis. Deletion of sol5 in both Ascochyta
      rabiei and Alternaria solani completely prevented production of solanapyrones and
      led to accumulation of the immediate precursor compound, prosolanapyrone II-diol,
      which is not toxic to plants. Deletion of sol5 did not negatively affect growth
      rate or spore production in vitro, and led to overexpression of the other
      solanapyrone biosynthesis genes, suggesting a possible feedback regulation
      mechanism. Phytotoxicity tests showed that solanapyrone A is highly toxic to
      several legume species and Arabidopsis thaliana. Despite the apparent
      phytotoxicity of solanapyrone A, pathogenicity tests showed that solanapyrone
      minus mutants of Ascochyta rabiei and Alternaria solani were equally virulent as
      their corresponding wild-type progenitors, suggesting that solanapyrones are not
      required for pathogenicity. 

PMID- 25372119
TI  - Identification of a 12-gene Fusaric Acid Biosynthetic Gene Cluster in Fusarium
      Species Through Comparative and Functional Genomics.
AB  - In fungi, genes involved in biosynthesis of a secondary metabolite (SM) are often
      located adjacent to one another in the genome and are coordinately regulated.
      These SM biosynthetic gene clusters typically encode enzymes, one or more
      transcription factors, and a transport protein. Fusaric acid is a polyketide
      derived SM produced by multiple species of the fungal genus Fusarium. This SM is
      of concern because it is toxic to animals and, therefore, is considered a
      mycotoxin and may contribute to plant pathogenesis. Preliminary descriptions of
      the fusaric acid (FA) biosynthetic gene (FUB) cluster have been reported in two
      Fusarium species, the maize pathogen F. verticillioides and the rice pathogen F.
      fujikuroi. The cluster consisted of five genes and did not include a
      transcription factor or transporter gene. Here, analysis of the FUB region in F.
      verticillioides, F. fujikuroi, and F. oxysporum, a plant pathogen with multiple
      hosts, indicates the FUB cluster consists of at least 12 genes (FUB1 to FUB12).
      Deletion analysis confirmed that nine FUB genes, including two Zn(II)2Cys6
      transcription factor genes, are required for production of wild-type levels of
      FA. Comparisons of FUB cluster homologs across multiple Fusarium isolates and
      species revealed insertion of non-FUB genes at one or two locations in some
      homologs. Although the ability to produce FA contributed to the phytotoxicity of
      F. oxysporum culture extracts, lack of production did not affect virulence of F.
      oxysporum on cactus or F. verticillioides on maize seedlings. These findings
      provide new insights into the genetic and biochemical processes required for FA
      production. 

PMID- 25372120
TI  - ALD1 Regulates Basal Immune Components and Early Inducible Defense Responses in
      Arabidopsis.
AB  - Robust immunity requires basal defense machinery to mediate timely responses and
      feedback cycles to amplify defenses against potentially spreading infections.
      AGD2-LIKE DEFENSE RESPONSE PROTEIN 1 (ALD1) is needed for the accumulation of the
      plant defense signal salicylic acid (SA) during the first hours after infection
      with the pathogen Pseudomonas syringae and is also upregulated by infection and
      SA. ALD1 is an aminotransferase with multiple substrates and products in vitro.
      Pipecolic acid (Pip) is an ALD1-dependent bioactive product induced by P.
      syringae. Here, we addressed roles of ALD1 in mediating defense amplification as
      well as the levels and responses of basal defense machinery. ALD1 needs immune
      components PAD4 and ICS1 (an SA synthesis enzyme) to confer disease resistance,
      possibly through a transcriptional amplification loop between them. Furthermore,
      ALD1 affects basal defense by controlling microbial-associated molecular pattern
      (MAMP) receptor levels and responsiveness. Vascular exudates from uninfected ALD1
      overexpressing plants confer local immunity to the wild type and ald1 mutants yet
      are not enriched for Pip. We infer that, in addition to affecting Pip
      accumulation, ALD1 produces non-Pip metabolites that play roles in immunity.
      Thus, distinct metabolite signals controlled by the same enzyme affect basal and
      early defenses versus later defense responses, respectively. 

PMID- 25372121
TI  - Melon necrotic spot virus Replication Occurs in Association with Altered
      Mitochondria.
AB  - Melon necrotic spot virus (MNSV) (genus Carmovirus, family Tombusviridae) is a
      single-stranded, positive-sense RNA virus that has become an experimental model
      for the analysis of cell-to-cell virus movement and translation of uncapped viral
      RNAs, whereas little is known about its replication. Analysis of the
      cytopathology after MNSV infection showed the specific presence of modified
      organelles that resemble mitochondria. Immunolocalization of the glycine
      decarboxylase complex (GDC) P protein in these organelles confirmed their
      mitochondrial origin. In situ hybridization and immunolocalization experiments
      showed the specific localization of positive-sense viral RNA, capsid protein
      (CP), and double-stranded (ds)RNA in these organelles meaning that replication of
      the virus takes place in association with them. The three-dimensional
      reconstructions of the altered mitochondria showed the presence of large,
      interconnected, internal dilations which appeared to be linked to the outside
      cytoplasmic environment through pores and/or complex structures, and with lipid
      bodies. Transient expression of MNSV p29 revealed that its specific target is
      mitochondria. Our data document the extensive reorganization of host mitochondria
      induced by MNSV, which provides a protected environment to viral replication, and
      show that the MNSV p29 protein is the primary determinant of this effect in the
      host. 

PMID- 25372122
TI  - Alternative Splicing in the Obligate Biotrophic Oomycete Pathogen
      Pseudoperonospora cubensis.
AB  - Pseudoperonospora cubensis is an obligate pathogen and causative agent of
      cucurbit downy mildew. To help advance our understanding of the pathogenicity of
      P. cubensis, we used RNA-Seq to improve the quality of its reference genome
      sequence. We also characterized the RNA-Seq dataset to inventory transcript
      isoforms and infer alternative splicing during different stages of its
      development. Almost half of the original gene annotations were improved and
      nearly 4,000 previously unannotated genes were identified. We also demonstrated
      that approximately 24% of the expressed genome and nearly 55% of the intron
      containing genes from P. cubensis had evidence for alternative splicing. Our
      analyses revealed that intron retention is the predominant alternative splicing
      type in P. cubensis, with alternative 5'- and alternative 3'-splice sites
      occurring at lower frequencies. Representatives of the newly identified genes and
      predicted alternatively spliced transcripts were experimentally validated. The
      results presented herein highlight the utility of RNA-Seq for improving draft
      genome annotations and, through this approach, we demonstrate that alternative
      splicing occurs more frequently than previously predicted. In total, the current
      study provides evidence that alternative splicing plays a key role in
      transcriptome regulation and proteome diversification in plant-pathogenic
      oomycetes. 

PMID- 25372123
TI  - The value of molecular diagnostics for indeterminate thyroid nodules.

PMID- 25372133
TI  - Linked Data Analysis of Dually Eligible Beneficiaries in New England.
AB  - Analysis of linked Medicare/Medicaid data files from four New England States
      (Connecticut, Maine, Massachusetts, and New Hampshire) confirm that dually
      eligible beneficiaries used a disproportionate amount of both Medicare and
      Medicaid resources in 1995, driven largely by the significant subset of the
      population that used institutional long-term care (LTC). If States and the
      Federal Government are successful in developing approaches to dually eligible
      beneficiaries that reduce the use of institutional LTC, overall public costs per
      person could decline while Federal costs remained constant, and beneficiaries
      could have a greater selection of community-based options and experience greater
      satisfaction.

PMID- 25372124
TI  - Perchlorate exposure in pregnancy and cognitive outcomes in children: it's not
      your mother's thyroid.

PMID- 25372135
TI  - Effective antibiotics against 'Candidatus Liberibacter asiaticus' in HLB-affected
      citrus plants identified via the graft-based evaluation.
AB  - Citrus huanglongbing (HLB), caused by three species of fastidious, phloem-limited
      'Candidatus Liberibacter', is one of the most destructive diseases of citrus
      worldwide. To date, there is no established cure for this century-old and yet,
      newly emerging disease. As a potential control strategy for citrus HLB, 31
      antibiotics were screened for effectiveness and phytotoxicity using the optimized
      graft-based screening system with 'Candidatus Liberibacter asiaticus' (Las)
      infected citrus scions. Actidione and Oxytetracycline were the most phytotoxic to
      citrus with less than 10% of scions surviving and growing; therefore, this data
      was not used in additional analyses. Results of principal component (PCA) and
      hierarchical clustering analyses (HCA) demonstrated that 29 antibiotics were
      clustered into 3 groups: highly effective, partly effective, and not effective.
      In spite of different modes of actions, a number of antibiotics such as,
      Ampicillin, Carbenicillin, Penicillin, Cefalexin, Rifampicin and Sulfadimethoxine
      were all highly effective in eliminating or suppressing Candidatus Liberibacter
      asiaticus indicated by both the lowest Las infection rate and titers of the
      treated scions and inoculated rootstock. The non-effective group, including 11
      antibiotics alone with three controls, such as Amikacin, Cinoxacin, Gentamicin,
      Kasugamycin, Lincomycin, Neomycin, Polymixin B and Tobramycin, did not eliminate
      or suppress Las in the tested concentrations, resulting in plants with increased
      titers of Las. The other 12 antibiotics partly eliminated or suppressed Las in
      the treated and graft-inoculated plants. The effective and non-phytotoxic
      antibiotics could be potential candidates for control of citrus HLB, either for
      the rescue of infected citrus germplasm or for restricted field application. 

PMID- 25372136
TI  - Multidimensional measures of impulsivity in obsessive-compulsive disorder: cannot
      wait and stop.
AB  - OBJECTIVE: Although the relationship between obsessive compulsive disorder (OCD)
      and impulsivity has long been debated, impulsivity has not been systematically
      examined in clinical samples of OCD. Meanwhile, recent findings suggest that
      impulsivity is multi-dimensional construct that can be examined through several
      constructs. Therefore, this study is aimed to evaluate multiple facets of
      impulsivity in OCD. METHOD: The recruitment includes 80 OCD and 76 healthy
      control participants. Participants completed a test battery comprising three
      behavioral tasks of stop signal task (SST), delay discounting task (DDT) and
      balloon analog risk test (BART), and one self-report measure of the Barratt
      Impulsiveness scale (BIS-11). RESULTS: OCD subjects showed significantly lower
      stop signal reaction time of SST reflecting higher action impulsivity and higher
      delay discounting parameter of DDT suggesting increased choice impulsivity but
      significantly lower adjusted mean pump of BART implying lower risk taking
      propensity of BART than healthy control. CONCLUSION: Increased Action and choice
      impulsivity, and decreased risk taking propensities were found in OCD. These
      findings seem to be consistent with clinical characteristics of OCD such as
      greater preference for or avoid risky situations (avoidance), inability to wait
      tension relief may provoke safety behaviors (compulsion) and inability to stop
      already started behaviors (repetition).

PMID- 25372137
TI  - Vegetable exudates as food for Callithrix spp. (Callitrichidae): exploratory
      patterns.
AB  - Marmosets of the genus Callithrix are specialized in the consumption of tree
      exudates to obtain essential nutritional resource by boring holes into bark with
      teeth. However, marmoset preferences for particular tree species, location, type,
      and other suitable factors that aid in exudate acquisition need further research.
      In the current study, the intensity of exudate use from Anadenanthera peregrina
      var. peregrina trees by hybrid marmosets Callithrix spp. groups was studied in
      five forest fragments in Vicosa, in the state of Minas, Brazil. Thirty-nine A.
      peregrina var. peregrina trees were examined and 8,765 active and non-active
      holes were analyzed. The trunk of A. peregrina var. peregrina had a lower number
      of holes than the canopy: 11% were found on the trunk and 89% were found on the
      canopy. The upper canopy was the preferred area by Callithrix spp. for obtaining
      exudates. The intensity of tree exploitation by marmosets showed a moderate-to
      weak correlation with diameter at breast height (DBH) and total tree height. The
      overall results indicate that Anadenanthera peregrina var. peregrina provides
      food resources for hybrid marmosets (Callithrix spp.) and these animals prefer to
      explore this resource on the apical parts of the plant, where the thickness,
      location, and age of the branches are the main features involved in the
      acquisition of exudates. 

PMID- 25372138
TI  - Computational state space models for activity and intention recognition. A
      feasibility study.
AB  - BACKGROUND: Computational state space models (CSSMs) enable the knowledge-based
      construction of Bayesian filters for recognizing intentions and reconstructing
      activities of human protagonists in application domains such as smart
      environments, assisted living, or security. Computational, i. e., algorithmic,
      representations allow the construction of increasingly complex human behaviour
      models. However, the symbolic models used in CSSMs potentially suffer from
      combinatorial explosion, rendering inference intractable outside of the limited
      experimental settings investigated in present research. The objective of this
      study was to obtain data on the feasibility of CSSM-based inference in domains of
      realistic complexity. METHODS: A typical instrumental activity of daily living
      was used as a trial scenario. As primary sensor modality, wearable inertial
      measurement units were employed. The results achievable by CSSM methods were
      evaluated by comparison with those obtained from established training-based
      methods (hidden Markov models, HMMs) using Wilcoxon signed rank tests. The
      influence of modeling factors on CSSM performance was analyzed via repeated
      measures analysis of variance. RESULTS: The symbolic domain model was found to
      have more than 10(8) states, exceeding the complexity of models considered in
      previous research by at least three orders of magnitude. Nevertheless, if factors
      and procedures governing the inference process were suitably chosen, CSSMs
      outperformed HMMs. Specifically, inference methods used in previous studies
      (particle filters) were found to perform substantially inferior in comparison to
      a marginal filtering procedure. CONCLUSIONS: Our results suggest that the
      combinatorial explosion caused by rich CSSM models does not inevitably lead to
      intractable inference or inferior performance. This means that the potential
      benefits of CSSM models (knowledge-based model construction, model reusability,
      reduced need for training data) are available without performance penalty.
      However, our results also show that research on CSSMs needs to consider
      sufficiently complex domains in order to understand the effects of design
      decisions such as choice of heuristics or inference procedure on performance.

PMID- 25372139
TI  - 17beta-estradiol modulates gene expression in the female mouse cerebral cortex.
AB  - 17beta-estradiol (E2) plays critical roles in a number of target tissues
      including the mammary gland, reproductive tract, bone, and brain. Although it is
      clear that E2 reduces inflammation and ischemia-induced damage in the cerebral
      cortex, the molecular mechanisms mediating the effects of E2 in this brain region
      are lacking. Thus, we examined the cortical transcriptome using a mouse model
      system. Female adult mice were ovariectomized and implanted with silastic tubing
      containing oil or E2. After 7 days, the cerebral cortices were dissected and RNA
      was isolated and analyzed using RNA-sequencing. Analysis of the transcriptomes of
      control and E2-treated animals revealed that E2 treatment significantly altered
      the transcript levels of 88 genes. These genes were associated with long term
      synaptic potentiation, myelination, phosphoprotein phosphatase activity, mitogen
      activated protein kinase, and phosphatidylinositol 3-kinase signaling. E2 also
      altered the expression of genes linked to lipid synthesis and metabolism,
      vasoconstriction and vasodilation, cell-cell communication, and histone
      modification. These results demonstrate the far-reaching and diverse effects of
      E2 in the cerebral cortex and provide valuable insight to begin to understand
      cortical processes that may fluctuate in a dynamic hormonal environment. 

PMID- 25372140
TI  - PDE5 inhibition improves object memory in standard housed rats but not in rats
      housed in an enriched environment: implications for memory models?
AB  - Drug effects are usually evaluated in animals housed under maximally standardized
      conditions. However, it is assumed that an enriched environment (EE) more closely
      resembles human conditions as compared to maximally standardized laboratory
      conditions. In the present study, we examined the acute cognition enhancing
      effects of vardenafil, a PDE5 inhibitor, which stimulates protein kinase G/CREB
      signaling in cells, in three different groups of male Wistar rats tested in an
      object recognition task (ORT). Rats were either housed solitarily (SOL) or
      socially (SOC) under standard conditions, or socially in an EE. Although EE
      animals remembered object information longer in the vehicle condition, vardenafil
      only improved object memory in SOL and SOC animals. While EE animals had a
      heavier dorsal hippocampus, we found no differences between experimental groups
      in total cell numbers in the dentate gyrus, CA2-3 or CA1. Neither were there any
      differences in markers for pre- and postsynaptic density. No changes in PDE5 mRNA
      and protein expression levels were observed. Basal pCREB levels were increased
      in EE rats only, whereas beta-catenin was not affected, suggesting specific
      activation of the MAP kinase signaling pathway and not the AKT pathway. A
      possible explanation for the inefficacy of vardenafil could be that CREB
      signaling is already optimally stimulated in the hippocampus of EE rats. Since
      previous data has shown that acute PDE5 inhibition does not improve memory
      performance in humans, the use of EE animals could be considered as a more valid
      model for testing cognition enhancing drugs. 

PMID- 25372141
TI  - Evaluation of cotton leaf curl virus resistance in BC1, BC2, and BC3 progenies
      from an interspecific cross between Gossypium arboreum and Gossypium hirsutum.
AB  - Cotton leaf curl virus disease (CLCuD) is an important constraint to cotton
      production. The resistance of G. arboreum to this devastating disease is well
      documented. In the present investigation, we explored the possibility of
      transferring genes for resistance to CLCuD from G. arboreum (2n = 26) cv 15
      Mollisoni into G. hirsutum (2n = 52) cv CRSM-38 through conventional breeding. We
      investigated the cytology of the BC1 to BC3 progenies of direct and reciprocal
      crosses of G. arboreum and G. hirsutum and evaluated their resistance to CLCuD.
      The F1 progenies were completely resistant to this disease, while a decrease in
      resistance was observed in all backcross generations. As backcrossing progressed,
      the disease incidence increased in BC1 (1.7-2.0%), BC2 (1.8-4.0%), and BC3 (4.2
      7.0%). However, the disease incidence was much lower than that of the check
      variety CIM-496, with a CLCuD incidence of 96%. Additionally, the disease
      incidence percentage was lower in the direct cross 2(G. arboreum)*G. hirsutum
      than in that of G. hirsutum*G. arboreum. Phenotypic resemblance of BC1 ~BC3
      progenies to G. arboreum confirmed the success of cross between the two species.
      Cytological studies of CLCuD-resistant plants revealed that the frequency of
      univalents and multivalents was high in BC1, with sterile or partially fertile
      plants, but low in BC2 (in both combinations), with shy bearing plants. In BC3,
      most of the plants exhibited normal bearing ability due to the high frequency of
      chromosome associations (bivalents). The assessment of CLCuD through grafting
      showed that the BC1 to BC3 progenies were highly resistant to this disease. Thus,
      this study successfully demonstrates the possibility of introgressing CLCuD
      resistance genes from G. arboreum to G. hirsutum. 

PMID- 25372142
TI  - Structure evolution of graphene oxide during thermally driven phase
      transformation: is the oxygen content really preserved?
AB  - A mild annealing procedure was recently proposed for the scalable enhancement of
      graphene oxide (GO) properties with the oxygen content preserved, which was
      demonstrated to be attributed to the thermally driven phase separation. In this
      work, the structure evolution of GO with mild annealing is closely investigated.
      It reveals that in addition to phase separation, the transformation of oxygen
      functionalities also occurs, which leads to the slight reduction of GO membranes
      and furthers the enhancement of GO properties. These results are further
      supported by the density functional theory based calculations. The results also
      show that the amount of chemically bonded oxygen atoms on graphene decreases
      gradually and we propose that the strongly physisorbed oxygen species constrained
      in the holes and vacancies on GO lattice might be responsible for the preserved
      oxygen content during the mild annealing procedure. The present experimental
      results and calculations indicate that both the diffusion and transformation of
      oxygen functional groups might play important roles in the scalable enhancement
      of GO properties. 

PMID- 25372143
TI  - Personality, relationship conflict, and teamwork-related mental models.
AB  - This study seeks to explore whether neuroticism, agreeableness, and
      conscientiousness moderate the influence of relationship conflict experienced in
      groups on changes in group members' evaluative cognitions related to teamwork
      quality (teamwork-related mental models). Data from 216 students, nested in 48
      groups were analyzed using a multilevel modeling approach. Our results show that
      the experience of relationship conflict leads to a negative shift from the pre
      task to the post-task teamwork-related mental models. Moreover, the results
      indicate that conscientiousness buffered the negative association between
      relationship conflict and the change in teamwork-related mental models. Our
      results did not support the hypothesized moderating effect of agreeableness and
      show that the detrimental effect of relationship conflict on the shift in
      teamwork-related mental models is accentuated for group members scoring low
      rather than high on neuroticism. These findings open new research venues for
      exploring the association between personality, coping styles and change in
      teamwork-related mental models. 

PMID- 25372145
TI  - Monocyte-derived dendritic cells from patients with dermatophytosis restrict the
      growth of Trichophyton rubrum and induce CD4-T cell activation.
AB  - Dermatophytes are the most common agents of superficial mycoses that are caused
      by mold fungi. Trichophyton rubrum is the most common pathogen causing
      dermatophytosis. The immunology of dermatophytosis is currently poorly
      understood. Recently, our group investigated the interaction of T. rubrum conidia
      with peritoneal mouse macrophages. We found that macrophages phagocytose T.
      rubrum conidia resulted in a down-modulation of class II major histocompatibility
      complex (MHC) antigens and in the expression of co-stimulatory molecules.
      Furthermore, it induced the production of IL-10, and T. rubrum conidia
      differentiated into hyphae that grew and killed the macrophages after 8 hrs of
      culture. This work demonstrated that dendritic cells (DCs) and macrophages, from
      patients or normal individuals, avidly interact with pathogenic fungus T. rubrum.
      The dermatophyte has two major receptors on human monocyte-derived DC: DC-SIGN
      and mannose receptor. In contrast macrophage has only mannose receptor that
      participates in the phagocytosis or bound process. Another striking aspect of
      this study is that unlike macrophages that permit rapid growth of T. rubrum,
      human DC inhibited the growth and induces Th activation. The ability of DC from
      patients to interact and kill T. rubrum and to present Ags to T cells suggests
      that DC may play an important role in the host response to T. rubrum infection by
      coordinating the development of cellular immune response. 

PMID- 25372144
TI  - Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large
      scale calcium imaging study with miniaturized fluorescence microscope.
AB  - Therapeutic drugs for cognitive and psychiatric disorders are often characterized
      by their molecular mechanism of action. Here we demonstrate a new approach to
      elucidate drug action on large-scale neuronal activity by tracking somatic
      calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically
      manipulated behaving mice. We used an adeno-associated viral vector to express
      the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII
      promoter and a miniaturized microscope to observe cellular dynamics. We
      visualized these dynamics with and without a systemic administration of Zolpidem,
      a GABAA agonist that is the most commonly prescribed drug for the treatment of
      insomnia in the United States. Despite growing concerns about the potential
      adverse effects of Zolpidem on memory and cognition, it remained unclear whether
      Zolpidem alters neuronal activity in the hippocampus, a brain area critical for
      cognition and memory. Zolpidem, when delivered at a dose known to induce and
      prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium
      transients after Zolpidem administration was significantly lower compared to
      vehicle treatment. To factor out the contribution of changes in locomotor or
      physiological conditions following Zolpidem treatment, we compared the cellular
      activity across comparable epochs matched by locomotor and physiological
      assessments. This analysis revealed significantly depressive effects of Zolpidem
      regardless of the animal's state. Individual hippocampal CA1 pyramidal cells
      differed in their responses to Zolpidem with the majority (~ 65%) significantly
      decreasing the rate of calcium transients, and a small subset (3%) showing an
      unexpected and significant increase. By linking molecular mechanisms with the
      dynamics of neural circuitry and behavioral states, this approach has the
      potential to contribute substantially to the development of new therapeutics for
      the treatment of CNS disorders.

PMID- 25372146
TI  - Effect of a one-off educational session about enterobiasis on knowledge,
      preventative practices, and infection rates among schoolchildren in South Korea.
AB  - Although health education has proven to be cost-effective in slowing the spread
      of enterobiasis, assessments of the effectiveness of health education to reduce
      infectious diseases specifically in children are rare. To evaluate the effect of
      health education on knowledge, preventative practices, and the prevalence of
      enterobiasis, 319 children from 16 classes were divided into experimental and
      control groups. Data were collected from May 2012 to March 2013. A 40-minute in
      class talk was given once in the experimental group. There were significant
      differences over the time in the mean scores for children's knowledge of
      Enterobius vermicularis infection in the intervention group compared to the
      control group (p<0.001). After the educational session, the score for knowledge
      about E. vermicularis infection increased from 60.2 +/- 2.32 to 92.7 +/- 1.19 in
      the experimental group; this gain was partially lost 3 months later, decreasing
      to 83.6 +/- 1.77 (p<0.001). Children's enterobiasis infection prevention practice
      scores also increased, from 3.23 +/- 0.27 to 3.73 +/- 0.25, 1 week after the
      educational session, a gain that was partially lost at 3 months, decreasing to
      3.46 +/- 0.36 (p<0.001). The overall E. vermicularis egg detection rate was 4.4%;
      the rates for each school ranged from 0% to 12.9% at screening. The infection
      rate at 3 months after the treatment sharply decreased from 12.3% to 0.8% in the
      experimental group, compared to a decrease from 8.5% to 3.7% in the control group
      during the same period. We recommend that health education on enterobiasis be
      provided to children to increase their knowledge about enterobiasis and improve
      prevention practices.

PMID- 25372147
TI  - Metrical presentation boosts implicit learning of artificial grammar.
AB  - The present study investigated whether a temporal hierarchical structure favors
      implicit learning. An artificial pitch grammar implemented with a set of tones
      was presented in two different temporal contexts, notably with either a strongly
      metrical structure or an isochronous structure. According to the Dynamic
      Attending Theory, external temporal regularities can entrain internal oscillators
      that guide attention over time, allowing for temporal expectations that influence
      perception of future events. Based on this framework, it was hypothesized that
      the metrical structure provides a benefit for artificial grammar learning in
      comparison to an isochronous presentation. Our study combined behavioral and
      event-related potential measurements. Behavioral results demonstrated similar
      learning in both participant groups. By contrast, analyses of event-related
      potentials showed a larger P300 component and an earlier N2 component for the
      strongly metrical group during the exposure phase and the test phase,
      respectively. These findings suggests that the temporal expectations in the
      strongly metrical condition helped listeners to better process the pitch
      dimension, leading to improved learning of the artificial grammar. 

PMID- 25372150
TI  - A high-resolution chronology of rapid forest transitions following polynesian
      arrival in New Zealand.
AB  - Human-caused forest transitions are documented worldwide, especially during
      periods when land use by dense agriculturally-based populations intensified.
      However, the rate at which prehistoric human activities led to permanent
      deforestation is poorly resolved. In the South Island, New Zealand, the arrival
      of Polynesians c. 750 years ago resulted in dramatic forest loss and conversion
      of nearly half of native forests to open vegetation. This transformation, termed
      the Initial Burning Period, is documented in pollen and charcoal records, but its
      speed has been poorly constrained. High-resolution chronologies developed with a
      series of AMS radiocarbon dates from two lake sediment cores suggest the shift
      from forest to shrubland occurred within decades rather than centuries at drier
      sites. We examine two sites representing extreme examples of the magnitude of
      human impacts: a drier site that was inherently more vulnerable to human-set
      fires and a wetter, less burnable site. The astonishing rate of deforestation at
      the hands of small transient populations resulted from the intrinsic
      vulnerability of the native flora to fire and from positive feedbacks in post
      fire vegetation recovery that increased landscape flammability. Spatially
      targeting burning in highly-flammable seral vegetation in forests rarely
      experiencing fire was sufficient to create an alternate fire-prone stable state.
      The New Zealand example illustrates how seemingly stable forest ecosystems can
      experience rapid and permanent conversions. Forest loss in New Zealand is among
      the fastest ecological transitions documented in the Holocene; yet equally rapid
      transitions can be expected in present-day regions wherever positive feedbacks
      support alternate fire-inhibiting, fire-prone stable states. 

PMID- 25372149
TI  - Efficacy of a group-based multimedia HIV prevention intervention for drug
      involved women under community supervision: project WORTH.
AB  - IMPORTANCE: This study is designed to address the need for evidence-based HIV/STI
      prevention approaches for drug-involved women under criminal justice community
      supervision. OBJECTIVE: We tested the efficacy of a group-based traditional and
      multimedia HIV/STI prevention intervention (Project WORTH: Women on the Road to
      Health) among drug-involved women under community supervision. DESIGN, SETTING,
      PARTICIPANTS, AND INTERVENTION: We randomized 306 women recruited from community
      supervision settings to receive either: (1) a four-session traditional group
      based HIV/STI prevention intervention (traditional WORTH); (2) a four-session
      multimedia group-based HIV/STI prevention intervention that covered the same
      content as traditional WORTH but was delivered in a computerized format; or (3) a
      four-session group-based Wellness Promotion intervention that served as an
      attention control condition. The study examined whether the traditional or
      multimedia WORTH intervention was more efficacious in reducing risks when
      compared to Wellness Promotion; and whether multimedia WORTH was more efficacious
      in reducing risks when compared to traditional WORTH. MAIN OUTCOMES AND MEASURES:
      Primary outcomes were assessed over the 12-month post-intervention period and
      included the number of unprotected sex acts, the proportion of protected sex
      acts, and consistent condom use. At baseline, 77% of participants reported
      unprotected vaginal or anal sex (n = 237) and 63% (n = 194) had multiple sex
      partners. RESULTS: Women assigned to traditional or multimedia WORTH were
      significantly more likely than women assigned to the control condition to report
      an increase in the proportion of protected sex acts (beta = 0.10; 95% CI = 0.02
      0.18) and a decrease in the number of unprotected sex acts (IRR = 0.72; 95% CI =
      0.57-0.90). CONCLUSION AND RELEVANCE: The promising effects of traditional and
      multimedia WORTH on increasing condom use and high participation rates suggest
      that WORTH may be scaled up to redress the concentrated epidemics of HIV/STIs
      among drug-involved women in the criminal justice system. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01784809.

PMID- 25372151
TI  - Etching of glass microchips with supercritical water.
AB  - A novel method of etching channels in glass microchips with the most tunable
      solvent, water, was tested as an alternative to common hydrogen fluoride
      containing etchants. The etching properties of water strongly depend on
      temperature and pressure, especially in the vicinity of the water critical point.
      The chips were etched at the subcritical, supercritical and critical temperature
      of water, and the resulting channel shape, width, depth and surface morphology
      were studied by scanning electron microscopy and 3D laser profilometry. Channels
      etched with the hot water were compared with the chips etched with standard
      hydrogen fluoride-containing solution. Depending on the water pressure and
      temperature, the silicate dissolved from the glass could be re-deposited on the
      channel surface. This interesting phenomenon is described together with the
      conditions necessary for its utilization. The results illustrate the versatility
      of pure water as a glass etching and surface morphing agent. 

PMID- 25372152
TI  - Guest-driven inflation of self-assembled nanofibers through hollow channel
      formation.
AB  - The highlight of self-assembly is the reversibility of various types of
      noncovalent interactions which leads to construct smart nanostructures with
      switchable pores. Here, we report the spontaneous formation of inflatable
      nanofibers through the formation of hollow internal channels triggered by guest
      encapsulation. The molecules that form this unique nanofibers consist of a bent
      shaped aromatic segment connected by a m-pyridine unit and a hydrophilic dendron
      at its apex. The aromatic segments self-assemble into paired dimers which stack
      on top of one another to form thin nanofibers with pyridine-functionalized
      aromatic cores. Notably, the nanofibers reversibly inflate into helical tubules
      through the formation of hollow cavities triggered by p-phenylphenol, a hydrogen
      bonding guest. The reversible inflation of the nanofibers arises from the packing
      rearrangements in the aromatic cores from transoid dimers to cisoid macrocycles
      driven by the reversible hydrogen-bonding interactions between the pyridine units
      of the aromatic cores and the p-phenylphenol guest molecules. 

PMID- 25372153
TI  - Synthetic access to the chemical diversity of DNA and RNA 5'-aldehyde lesions.
AB  - Hydrogen atom abstraction from the C5'-position of nucleotides in DNA results in
      direct strand scission by generating alkali-labile fragments from the oxidized
      nucleotide. The major damage consists in a terminus containing a 5'-aldehyde as
      part of an otherwise undamaged nucleotide. Moreover it is considered as a
      polymorphic DNA strand break lesion since it can be borne by any of the four
      nucleosides encountered in DNA. Here we propose an expeditious synthesis of
      oligonucleotides (ON) ending with this 5'-aldehyde group (5'-AODN). This
      straightforward and cheap strategy relies on Pfitzner-Moffatt oxidation performed
      on solid support followed by a transient protection of the resulting aldehyde
      function. This method is irrespective of the 5'-terminal nucleobase and most
      interestingly can be directly extended to RNA to produce the corresponding 5'
      AORN. We also report preliminary results on recognition of 5'-AODN by base
      excision repair (BER) enzymes.

PMID- 25372154
TI  - Crown ethers attenuate aggregation of amyloid beta of Alzheimer's disease.
AB  - In this report, we reasoned that non-covalent modification of amyloid beta
      (Abeta) by crown ethers could inhibit its aggregation. We demonstrated that PiB
      C, a conjugate PiB and crown ether, could significantly reduce the aggregation in
      vitro. Additionally, two-photon imaging showed that PiB-C could efficiently label
      Abeta plaques and CAAs in AD mice. 

PMID- 25372155
TI  - The synthesis of 3-hydroxy-2,4,8-trimethyldec-8-enolides and an approach to 3,4
      dihydroxy-2,4,6,8-tetramethyldec-8-enolide.
AB  - The synthesis of several derivatives of 3-hydroxy-2,4,8-trimethyldec-8-enolide
      and attempts at the synthesis of 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide
      (1), a structure which has been assigned to a metabolite of the phytopathogenic
      fungus, Botrytis cinerea, gave products whose spectroscopic data had significant
      differences from those reported for the natural product 1. The rare 11-membered
      lactone rings were constructed by ring-closing metathesis reactions. The increase
      in conformational restrictions imposed by the substituents has a high influence
      on the stereochemistry of the ring-closing metathesis reaction and gives rise to
      a decrease in the yield for the synthesis of 11-membered lactones. The
      predominant alkene which was obtained was the (Z)-isomer. The observed
      spectroscopic differences between the synthesized lactones and the natural
      product and the spectroscopic data of its acetylated derivative 26a allowed us to
      revise the structure 1 to that of the gamma-butyrolactone 26. 

PMID- 25372156
TI  - Supramolecular hybrid hydrogel based on host-guest interaction and its
      application in drug delivery.
AB  - In this work, we developed a simple, novel method for constructing gold
      nanocomposite supramolecular hybrid hydrogels for drug delivery, in which gold
      nanocrystals were utilized as building blocks. First, methoxypoly(ethylene
      glycol) thiol (mPEG-SH, molecular weight (MW)=5 K) capped gold nanocrystals
      (nanospheres and nanorods) were prepared via a facile one-step ligand-exchange
      procedure. Then, the homogeneous supramolecular hybrid hydrogels were formed,
      after adding alpha-cyclodextrin (alpha-CD) into PEG-modified gold nanocrystal
      solutions, due to the host-guest inclusion. Both gold nanoparticles and inclusion
      complexes formed between alpha-CD and PEG chain provided the supra-cross-links,
      which are beneficial to the gelation formation. The resulting hybrid hydrogels
      were fully characterized by a combination of techniques including X-ray
      diffraction, rheology studies, and scanning electron microscopy. Meanwhile, the
      hybrid hydrogel systems demonstrated unique reversible gel-sol transition
      properties at a certain temperature caused by the temperature-responsive
      reversible supramolecular assembly. The drug delivery applications of such hybrid
      hydrogels were further investigated in which doxorubicin was selected as a model
      drug for in vitro release, cytotoxicity, and intracellular release studies. We
      believe that the development of such hybrid hydrogels will provide new and
      therapeutically useful means for medical applications.

PMID- 25372157
TI  - Prospective payment for Medicare hospital capital: Implications of the research.
AB  - The special characteristics of capital have an important effect on the cross
      section variation in hospitals' capital costs. Variables reflecting capital age
      and financing differences perform as expected and add substantial explanatory
      power to capital cost models. However, even with the inclusion of these
      variables, the capital-cost models perform poorly compared with total-cost
      models. The empirical findings of this article support using the total-cost
      models to develop a common set of adjustment factors for capital and operating
      payment amounts in the Medicare prospective payment system.

PMID- 25372158
TI  - The subpetrous carotid wall hematoma: a sign of spontaneous dissection of the
      internal carotid artery on non-enhanced computed tomography - a retrospective
      study.
AB  - PURPOSE: Spontaneous dissection of the internal carotid artery (CAD) is an
      increasingly recognized cause for stroke especially in young and middle-aged
      patients. We hypothesized that non-enhanced cranial computed tomography (NECCT)
      can visualize the subpetrous carotid wall hematoma and thus enable identification
      of patients with CAD. MATERIALS AND METHODS: We retrospectively reviewed patients
      with confirmed CAD (n = 21) and a control group with ischemic symptoms but
      without CAD (n = 42) who received NECCT at admission. Two independent
      neuroradiologists rated the presence and shape of SPH, density and diameter of
      the subpetrous internal carotid artery. Additionally, we correlated the shape of
      the subpetrous carotid wall hematoma with the grade of stenosis on subsequent
      angiographic imaging. RESULTS: The subpetrous carotid wall hematoma was present
      in 14 of 21 patients (Cohen's kappa = 0.67). Mean diameter was 6.95 +/- 1.05 mm
      in dissected vessels and 5.71 +/- 1.52 mm in the contralateral vessel (p < 0.05).
      Mean difference in vessel density was 15.05 +/- 8.01 HU (p < 0.01). Median grade
      of stenosis was significantly higher in patients with a full moon- shaped (n =
      11) than crescent-shaped (n = 3) subpetrous carotid wall hematoma (21 % vs. 80 %,
      p < 0.05). CONCLUSION: Two-thirds of patients with CAD  were correctly identified
      on NECCT. The extracranial carotid artery should be evaluated in patients with
      symptoms of cerebral ischemia.

PMID- 25372159
TI  - Radiologic management of haemoptysis: diagnostic and interventional bronchial
      arterial embolisation.
AB  - Hemoptysis can be a life-threatening pulmonary emergency with high mortality, is
      symptomatic of an underlying severe pulmonary disease and requires immediate
      diagnosis and treatment. Diagnostically, bronchoscopy, conventional chest x-ray
      and contrast-enhanced multislice computed tomography (MSCT) with CT angiography
      (CTA) provide information regarding the underlying pulmonary disease, bleeding
      site, the vascular anatomy of the bronchial arteries (BA) and extrabronchial
      branches, as well a basis for planning of endovascular intervention.
      Therapeutically, bronchial artery embolization (BAE) is a safe and effective
      technique in the hands of an experienced interventionist with profound knowledge
      of the BA anatomy and possible pitfalls as well as experience with first-line
      therapy of recurrent and massive hemoptysis or as an intervention prior to
      elective surgery. Recurrent episodes of hemoptysis are not uncommon and require a
      prompt repeat BAE after exclusion of extrabronchial systemic and pulmonary artery
      bleeding sources. This review article should give an overview of the history,
      anatomical and pathophysiological basics and the clinical context of hemoptysis
      and diagnosis, as well as a survey of management, treatment and results of BAE.
      KEY POINTS: Hemoptyses are life threatening and require urgent diagnostic and
      therapy. Chest x-ray, bronchoscopy, and contrast-enhanced MSCT with CTA should be
      carried out before therapeutic bronchial artery embolization (BAE). BAE for the
      treatment of massive and recurrent hemoptysis is safe and effective. False
      embolization in spinal branches of BA are the most serious complication of a BAE.
      Repeatedly BAE refractory cases should undergo elective surgery.

PMID- 25372160
TI  - [Long segment intussusception in solitary Peutz-Jeghers polyp in a pediatric
      patient].

PMID- 25372161
TI  - Dimensions of self-rated health in older adults.
AB  - OBJECTIVE: To analyze the association between negative self-rated health and
      indicators of health, wellbeing and sociodemographic variables in older adults.
      METHODS: Cross-sectional study that used data from a population-based health
      survey with a probability cluster sample that was carried out in Campinas, SP,
      Southeastern Brazil,, in 2008 and 2009. The participants were older adults (>= 60
      years) and the dependent variable was self-rated health, categorized as:
      excellent, very good, good, bad and very bad. The adjusted prevalence ratios were
      estimated by means of Poisson multiple regression. RESULTS: The highest
      prevalences of bad/very bad self-rated health were observed in the individuals
      who never attended school, in those with lower level of schooling, with monthly
      per capita family income lower than one minimum salary. Individuals who scored
      five or more in the physical health indicator also had bad self-rated health, as
      well as those who scored five or more in the Self-Reporting Questionnaire 20 and
      those who did not refer feeling happiness all the time. CONCLUSIONS: The
      independent effects of material life conditions, physical and mental health and
      subjective wellbeing, observed in self-rated health, suggest that older adults
      can benefit by health policies supported by a global and integrative view of old
      age.

PMID- 25372163
TI  - Formal caregivers of older adults: reflection about their practice.
AB  - OBJECTIVE: To understand the job function of caregivers of older adults and
      contribute to the debate on the consolidation of this professional practice.
      METHODOLOGICAL PROCEDURES: This is a descriptive, qualitative, and exploratory
      study. Four focal group sessions were performed in 2011 with 11 elderly
      companions, formal caregivers of older adults in the Programa Acompanhante de
      Idosos (Program for Caregivers of Older Adults), Sao Paulo, SP, Southeastern
      Brazil. These sessions, guided by a semi-structured script, were audio-recorded
      and fully transcribed. Data were analyzed using the Content Analysis technique,
      Thematic Modality. RESULTS: In view of considering the caregivers of older adults
      as a new category of workers, it was difficult to define their duties. The
      elderly companions themselves as well as the care receivers, their families, and
      the professionals that comprised the team were unclear about their duties. The
      professional practice of these formal caregivers has been built on the basis of
      constant discussions and negotiations among them and other team members in
      Programa Acompanhante de Idosos during daily work. This was achieved via a
      recognition process of their job functions and by setting apart other workers'
      exclusive responsibilities. CONCLUSIONS: The delimitation of specific job
      functions for elderly companions is currently one of the greatest challenges
      faced by these workers to develop and consolidate their professional role as well
      as improve Programa Acompanhante de Idosos.

PMID- 25372162
TI  - Prevalence of anemia and associated factors in older adults: evidence from the
      SABE Study.
AB  - OBJECTIVE: To assess the prevalence of anemia and associated factors in older
      adults. METHODS: The prevalence and factors associated with anemia in older
      adults were studied on the basis of the results of the Saude, Bem-Estar e
      Envelhecimento (SABE--Health, Welfare and Aging) study. A group of 1,256
      individuals were interviewed during the third wave of the SABE study performed in
      Sao Paulo, SP, in 2010. The study included 60.4% females; the mean age of the
      participants was 70.4 years, and their average education was 5.3 years. The
      dependent variable was the presence of anemia (hemoglobin levels: 12 g/dL in
      women and 13 g/dL in men). Descriptive analysis and hierarchical logistic
      regression were performed. The independent variables were as follows: (a)
      demographics: gender, age, and education and (b) clinical characteristics: self
      reported chronic diseases, presence of cognitive decline and depression symptoms,
      and body mass index. RESULTS: The prevalence of anemia was 7.7% and was found to
      be higher in oldest adults. There was no difference between genders, although the
      hemoglobin distribution curve in women showed a displacement toward lower values
      in comparison with the distribution curve in men. Advanced age (OR = 1.07; 95% CI
      0.57; 1.64; p < 0.001), presence of diabetes (OR = 2.30; 95% CI 1.33; 4.00; p =
      0.003), cancer (OR = 2.72; 95% CI 1.2; 6.11; p = 0.016), and presence of
      depression symptoms (OR = 1.75; 95% CI 1.06; 2.88; p = 0.028) remained
      significant even after multiple analyses. CONCLUSIONS: The prevalence of anemia
      in older adults was 7.7% and was mainly associated with advanced age and presence
      of chronic diseases. Thus, anemia can be an important marker in the investigation
      of health in older adults because it can be easily diagnosed and markedly affects
      the quality of life of older adults.

PMID- 25372164
TI  - Social capital, social participation and life satisfaction among Chilean older
      adults.
AB  - OBJECTIVE: To examine factors associated with social participation and their
      relationship with self-perceived well-being in older adults. METHODS: This study
      was based on data obtained from the National Socioeconomic Characterization
      (CASEN) Survey conducted in Chile, in 2011, on a probability sample of
      households. We examined information of 31,428 older adults living in these
      households. Descriptive and explanatory analyses were performed using linear and
      multivariate logistic regression models. We assessed the respondents'
      participation in different types of associations: egotropic, sociotropic, and
      religious. RESULTS: Social participation increased with advancing age and then
      declined after the age of 80. The main finding of this study was that family
      social capital is a major determinant of social participation of older adults.
      Their involvement was associated with high levels of self-perceived subjective
      well-being. We identified four settings as sources of social participation: home
      based; rural community-based; social policy programs; and religious. Older adults
      were significantly more likely to participate when other members of the household
      were also involved in social activities evidencing an intergenerational
      transmission of social participation. Rural communities, especially territorial
      associations, were the most favorable setting for participation. There has been a
      steady increase in the rates of involvement of older adults in social groups in
      Chile, especially after retirement. Religiosity remains a major determinant of
      associativism. The proportion of participation was higher among older women than
      men but these proportions equaled after the age of 80. CONCLUSIONS: Self
      perceived subjective well-being is not only dependent upon objective factors such
      as health and income, but is also dependent upon active participation in social
      life, measured as participation in associations, though its effects are moderate.

PMID- 25372165
TI  - Back pain in adults living in quilombola territories of Bahia, Northeastern
      Brazil.
AB  - OBJECTIVE: To analyze the factors associated with back pain in adults who live in
      quilombola territories. METHODS: A population-based survey was performed on
      quilombola communities of Vitoria da Conquista, state of Bahia, Northeastern
      Brazil. The sample (n = 750) was established via a raffle of residences. Semi
      structured interviews were conducted to investigate sociodemographics and
      employment characteristics, lifestyle, and health conditions. The outcome was
      analyzed as a dichotomous variable (Poisson regression). RESULTS: The prevalence
      of back pain was of 39.3%. Age >= 30 years and being a smoker were associated
      with the outcome. The employment status was not related to back pain.
      CONCLUSIONS: The survey identified a high prevalence of back pain in adults. It
      is suggested to support the restructuring of the local public service in order to
      outline programs and access to healthy practices, assistance, diagnosis, and
      treatment of spine problems.

PMID- 25372166
TI  - Women with HIV: gender violence and suicidal ideation.
AB  - OBJECTIVE: To analyze the relationship between gender violence and suicidal
      ideation in women with HIV. METHODS: A cross-sectional study with 161 users of
      specialized HIV/AIDS care services. The study investigated the presence of gender
      violence through the Brazilian version of the World Health Organization Violence
      against Women instrument, and suicidal ideation through the Suicidal Ideation
      Questionnaire. Statistical analyses were performed with the SPSS software, using
      the Chi-square test and Poisson multiple regression model. RESULTS: Eighty-two
      women with HIV reported suicidal ideation (50.0%), 78 (95.0%) of who had suffered
      gender violence. Age at first sexual intercourse < 15 years old, high number of
      children, poverty, living with HIV for long, and presence of violence were
      statistically associated with suicidal ideation. Women who suffered gender
      violence showed 5.7 times more risk of manifesting suicidal ideation.
      CONCLUSIONS: Women with HIV showed a high prevalence to gender violence and
      suicidal ideation. Understanding the relationship between these two grievances
      may contribute to the comprehensive care of these women and implementation of
      actions to prevent violence and suicide.

PMID- 25372167
TI  - Prevalence of syphilis in pregnancy and prenatal syphilis testing in Brazil:
      birth in Brazil study.
AB  - OBJECTIVE: Determine the coverage rate of syphilis testing during prenatal care
      and the prevalence of syphilis in pregnant women in Brazil. METHODS: This is a
      national hospital-based cohort study conducted in Brazil with 23,894 postpartum
      women between 2011 and 2012. Data were obtained using interviews with postpartum
      women, hospital records, and prenatal care cards. All postpartum women with a
      reactive serological test result recorded in the prenatal care card or syphilis
      diagnosis during hospitalization for childbirth were considered cases of syphilis
      in pregnancy. The Chi-square test was used for determining the disease prevalence
      and testing coverage rate by region of residence, self-reported skin color,
      maternal age, and type of prenatal and child delivery care units. RESULTS:
      Prenatal care covered 98.7% postpartum women. Syphilis testing coverage rate was
      89.1% (one test) and 41.2% (two tests), and syphilis prevalence in pregnancy was
      1.02% (95% CI 0.84; 1.25). A lower prenatal coverage rate was observed among
      women in the North region, indigenous women, those with less education, and those
      who received prenatal care in public health care units. A lower testing coverage
      rate was observed among residents in the North, Northeast, and Midwest regions,
      among younger and non-white skin-color women, among those with lower education,
      and those who received prenatal care in public health care units. An increased
      prevalence of syphilis was observed among women with < 8 years of education
      (1.74%), who self-reported as black (1.8%) or mixed (1.2%), those who did not
      receive prenatal care (2.5%), and those attending public (1.37%) or mixed (0.93%)
      health care units. CONCLUSIONS: The estimated prevalence of syphilis in pregnancy
      was similar to that reported in the last sentinel surveillance study conducted in
      2006. There was an improvement in prenatal care and testing coverage rate, and
      the goals suggested by the World Health Organization were achieved in two
      regions. Regional and social inequalities in access to health care units, coupled
      with other gaps in health assistance, have led to the persistence of congenital
      syphilis as a major public health problem in Brazil.

PMID- 25372168
TI  - Resistance of Aedes aegypti to temephos and adaptive disadvantages.
AB  - OBJECTIVE: To evaluate the resistance of Aedes aegypti to temephos Fersol 1G
      (temephos 1% w/w) associated with the adaptive disadvantage of insect populations
      in the absence of selection pressure. METHODS: A diagnostic dose of 0.28 mg
      a.i./L and doses between 0.28 mg a.i./L and 1.40 mg a.i./L were used. Vector
      populations collected between 2007 and 2008 in the city of Campina Grande, state
      of Paraiba, were evaluated. To evaluate competition in the absence of selection
      pressure, insect populations with initial frequencies of 20.0%, 40.0%, 60.0%, and
      80.0% resistant individuals were produced and subjected to the diagnostic dose
      for two months. Evaluation of the development of aquatic and adult stages allowed
      comparison of the life cycles in susceptible and resistant populations and
      construction of fertility life tables. RESULTS: No mortality was observed in Ae.
      aegypti populations subjected to the diagnostic dose of 0.28 mg a.i./L. The
      decreased mortality observed in populations containing 20.0%, 40.0%, 60.0%, and
      80.0% resistant insects indicates that temephos resistance is unstable in the
      absence of selection pressure. A comparison of the life cycles indicated
      differences in the duration and viability of the larval phase, but no differences
      were observed in embryo development, sex ratio, adult longevity, and number of
      eggs per female. CONCLUSIONS: The fertility life table results indicated that
      some populations had reproductive disadvantages compared with the susceptible
      population in the absence of selection pressure, indicating the presence of a
      fitness cost in populations resistant to temephos.

PMID- 25372169
TI  - Proposal of a short-form version of the Brazilian food insecurity scale.
AB  - OBJECTIVE: To propose a short version of the Brazilian Food Insecurity Scale.
      METHODS: Two samples were used to test the results obtained in the analyses in
      two distinct scenarios. One of the studies was composed of 230 low income
      families from Pelotas, RS, Southern Brazil, and the other was composed of 15,575
      women, whose data were obtained from the 2006 National Survey on Demography and
      Health. Two models were tested, the first containing seven questions, and the
      second, the five questions that were considered the most relevant ones in the
      concordance analysis. The models were compared to the Brazilian Food Insecurity
      Scale, and the sensitivity, specificity and accuracy parameters were calculated,
      as well as the kappa agreement test. RESULTS: Comparing the prevalence of food
      insecurity between the Brazilian Food Insecurity Scale and the two models, the
      differences were around 2 percentage points. In the sensitivity analysis, the
      short version of seven questions obtained 97.8% and 99.5% in the Pelotas sample
      and in the National Survey on Demography and Health sample, respectively, while
      specificity was 100% in both studies. The five-question model showed similar
      results (sensitivity of 95.7% and 99.5% in the Pelotas sample and in the National
      Survey on Demography and Health sample, respectively). In the Pelotas sample, the
      kappa test of the seven-question version totaled 97.0% and that of the five
      question version, 95.0%. In the National Survey on Demography and Health sample,
      the two models presented a 99.0% kappa. CONCLUSIONS: We suggest that the model
      with five questions should be used as the short version of the Brazilian Food
      Insecurity Scale, as its results were similar to the original scale with a lower
      number of questions. This version needs to be administered to other populations
      in Brazil in order to allow for the adequate assessment of the validity
      parameters.

PMID- 25372170
TI  - Audiometric profile of civilian pilots according to noise exposure.
AB  - OBJECTIVE: To evaluate the audiometric profile of civilian pilots according to
      the noise exposure level. METHODS: This observational cross-sectional study
      evaluated 3,130 male civilian pilots aged between 17 and 59 years. These pilots
      were subjected to audiometric examinations for obtaining or revalidating the
      functional capacity certificate in 2011. The degree of hearing loss was
      classified as normal, suspected noise-induced hearing loss, and no suspected
      hearing loss with other associated complications. Pure-tone air-conduction
      audiometry was performed using supra-aural headphones and acoustic stimulus of
      the pure-tone type, containing tone thresholds of frequencies between 250 Hz and
      6,000 Hz. The independent variables were professional categories, length of
      service, hours of flight, and right or left ear. The dependent variable was
      pilots with suspected noise-induced hearing loss. The noise exposure level was
      considered low/medium or high, and the latter involved periods > 5,000 flight
      hours and > 10 years of flight service. RESULTS: A total of 29.3% pilots had
      suspected noise-induced hearing loss, which was bilateral in 12.8% and
      predominant in the left ear (23.7%). The number of pilots with suspected hearing
      loss increased as the noise exposure level increased. CONCLUSIONS: Hearing loss
      in civilian pilots may be associated with noise exposure during the period of
      service and hours of flight.

PMID- 25372171
TI  - The influence of health expenditures on household impoverishment in Brazil.
AB  - OBJECTIVE: To analyze the variation in the proportion of households living below
      the poverty line in Brazil and the factors associated with their impoverishment.
      METHODS: Income and expenditure data from the Household Budget Survey, which was
      conducted in Brazil between 2002-2003 (n = 48,470 households) and 2008-2009 (n =
      55,970 households) with a national sample, were analyzed. Two cutoff points were
      used to define poverty. The first cutoff is a per capita monthly income below
      R$100.00 in 2002-2003 and R$140.00 in 2008-2009, as recommended by the Bolsa
      Familia Program. The second, which is proposed by the World Bank and is adjusted
      for purchasing power parity, defines poverty as per capita income below US$2.34
      and US$3.54 per day in 2002-2003 and 2008-2009, respectively. Logistic regression
      was used to identify the sociodemographic factors associated with the
      impoverishment of households. RESULTS: After subtracting health expenditures,
      there was an increase in households living below the poverty line in Brazil.
      Using the World Bank poverty line, the increase in 2002-2003 and 2008-2009 was
      2.6 percentage points (6.8%) and 2.3 percentage points (11.6%), respectively.
      Using the Bolsa Familia Program poverty line, the increase was 1.6 (11.9%) and
      1.3 (17.3%) percentage points, respectively. Expenditure on prescription drugs
      primarily contributed to the increase in poor households. According to the World
      Bank poverty line, the factors associated with impoverishment include a worse-off
      financial situation, a household headed by an individual with low education, the
      presence of children, and the absence of older adults. Using the Bolsa Familia
      Program poverty line, the factors associated with impoverishment include a worse
      off financial situation and the presence of children. CONCLUSIONS: Health
      expenditures play an important role in the impoverishment of segments of the
      Brazilian population, especially among the most disadvantaged.

PMID- 25372172
TI  - Legal and health variations in drug litigation injunctions granted in Minas
      Gerais.
AB  - OBJECTIVE: To investigate the factors related to the granting of preliminary
      court orders [injunctions] in drug litigations. METHODS: A retrospective
      descriptive study of drug lawsuits in the State of Minas Gerais, Southeastern
      Brazil, was conducted from October 1999 to 2009. The database consists of 6,112
      lawsuits, out of which 6,044 had motions for injunctions and 5,167 included the
      requisition of drugs. Those with more than one beneficiary were excluded, which
      totaled 5,072 examined suits. The variables for complete, partial, and suppressed
      motions were treated as dependent and assessed in relation to those that were
      independent--lawsuits (year, type, legal representation, defendant, court in
      which it was filed, adjudication time), drugs (level five of the anatomical
      therapeutic chemical classification), and diseases (chapter of the International
      Classification of Diseases). Statistical analyses were performed using the Chi
      square test. RESULTS: Out of the 5,072 lawsuits with injunctions, 4,184 (82.5%)
      had the injunctions granted. Granting varied from 95.8% of the total lawsuits in
      2004 to 76.9% in 2008. Where there was legal representation, granting exceeded
      80.0% and in lawsuits without representation, it did not exceed 66.9%. In public
      civil actions (89.1%), granting was higher relative to ordinary lawsuits (82.8%)
      and injunctions (80.1%). Federal courts granted only 68.6% of the injunctions,
      while the state courts granted 84.8%. Diseases of the digestive system and
      neoplasms received up to 87.0% in granting, while diseases of the nervous system,
      mental and behavioral disorders, and diseases of the skin and subcutaneous tissue
      received granting below 78.6% and showed a high proportion of suspended
      injunctions (10.9%). Injunctions involving paroxetine, somatropin, and ferrous
      sulfate drugs were all granted, while less than 54.0% of those involving
      escitalopram, sodium diclofenac, and nortriptyline were granted. CONCLUSIONS:
      There are significant differences in the granting of injunctions, depending on
      the procedural and clinical variances. Important trends in the pattern of
      judicial action were observed, particularly, in the reduced granting [of
      injunctions] over the period.

PMID- 25372173
TI  - Hospitalization of older adults due to ambulatory care sensitive conditions.
AB  - OBJECTIVE: To analyze the temporal evolution of the hospitalization of older
      adults due to ambulatory care sensitive conditions according to their structure,
      magnitude and causes. METHODS: Cross-sectional study based on data from the
      Hospital Information System of the Brazilian Unified Health System and from the
      Primary Care Information System, referring to people aged 60 to 74 years living
      in the state of Rio de Janeiro, Souhteastern Brazil. The proportion and rate of
      hospitalizations due to ambulatory care sensitive conditions were calculated,
      both the global rate and, according to diagnoses, the most prevalent ones. The
      coverage of the Family Health Strategy and the number of medical consultations
      attended by older adults in primary care were estimated. To analyze the
      indicators' impact on hospitalizations, a linear correlation test was used.
      RESULTS: We found an intense reduction in hospitalizations due to ambulatory care
      sensitive conditions for all causes and age groups. Heart failure,
      cerebrovascular diseases and chronic obstructive pulmonary diseases concentrated
      50.0% of the hospitalizations. Adults older than 69 years had a higher risk of
      hospitalization due to one of these causes. We observed a higher risk of
      hospitalization among men. A negative correlation was found between the
      hospitalizations and the indicators of access to primary care. CONCLUSIONS:
      Primary healthcare in the state of Rio de Janeiro has been significantly
      impacting the hospital morbidity of the older population. Studies of
      hospitalizations due to ambulatory care sensitive conditions can aid the
      identification of the main causes that are sensitive to the intervention of the
      health services, in order to indicate which actions are more effective to reduce
      hospitalizations and to increase the population's quality of life.

PMID- 25372174
TI  - Model for the evaluation of drug-dispensing services in primary health care.
AB  - OBJECTIVE: To develop a model for evaluating the efficacy of drug-dispensing
      service in primary health care. METHODS: An efficacy criterion was adopted to
      determine the level of achievement of the service objectives. The evaluation
      model was developed on the basis of a literature search and discussions with
      experts. The applicability test of the model was conducted in 15 primary health
      care units in the city of Florianopolis, state of Santa Catarina, in 2010, and
      data were recorded in structured and pretested questionnaires. RESULTS: The model
      developed was evaluated using five dimensions of analysis for analysis. The model
      was suitable for evaluating service efficacy and helped to identify the critical
      points of each service dimension. CONCLUSIONS: Adaptations to the data collection
      technique may be required to adjust for the reality and needs of each situation.
      The evaluation of the drug-dispensing service should promote adequate access to
      medications supplied through the public health system.

PMID- 25372175
TI  - Prevalence of health promotion programs in primary health care units in Brazil.
AB  - OBJECTIVE: Assessment of prevalence of health promotion programs in primary
      health care units within Brazil's health system. METHODS: We conducted a cross
      sectional descriptive study based on telephone interviews with managers of
      primary care units. Of a total 42,486 primary health care units listed in the
      Brazilian Unified Health System directory, 1,600 were randomly selected. Care
      units from all five Brazilian macroregions were selected proportionally to the
      number of units in each region. We examined whether any of the following five
      different types of health promotion programs was available: physical activity;
      smoking cessation; cessation of alcohol and illicit drug use; healthy eating; and
      healthy environment. Information was collected on the kinds of activities offered
      and the status of implementation of the Family Health Strategy at the units.
      RESULTS: Most units (62.0%) reported having in place three health promotion
      programs or more and only 3.0% reported having none. Healthy environment (77.0%)
      and healthy eating (72.0%) programs were the most widely available; smoking and
      alcohol use cessation were reported in 54.0% and 42.0% of the units. Physical
      activity programs were offered in less than 40.0% of the units and their
      availability varied greatly nationwide, from 51.0% in the Southeast to as low as
      21.0% in the North. The Family Health Strategy was implemented in most units
      (61.0%); however, they did not offer more health promotion programs than others
      did. CONCLUSIONS: Our study showed that most primary care units have in place
      health promotion programs. Public policies are needed to strengthen primary care
      services and improve training of health providers to meet the goals of the agenda
      for health promotion in Brazil.

PMID- 25372176
TI  - Handling random errors and biases in methods used for short-term dietary
      assessment.
AB  - Epidemiological studies have shown the effect of diet on the incidence of chronic
      diseases; however, proper planning, designing, and statistical modeling are
      necessary to obtain precise and accurate food consumption data. Evaluation
      methods used for short-term assessment of food consumption of a population, such
      as tracking of food intake over 24h or food diaries, can be affected by random
      errors or biases inherent to the method. Statistical modeling is used to handle
      random errors, whereas proper designing and sampling are essential for
      controlling biases. The present study aimed to analyze potential biases and
      random errors and determine how they affect the results. We also aimed to
      identify ways to prevent them and/or to use statistical approaches in
      epidemiological studies involving dietary assessments. 

PMID- 25372178
TI  - Photoluminescent and magnetic properties of lanthanide containing apatites:
      NaxLn10-x(SiO4)6O2-yFy, CaxLn10-x(SiO4)6O2-yFy (Ln = Eu, Gd, and Sm),
      Gd9.34(SiO4)6O2, and K1.32Pr8.68(SiO4)6O1.36F0.64.
AB  - Single crystals of NaEu(9)(SiO(4))(6)O(2), Na(1.5)Eu(8.5)(SiO(4))(6)OF,
      Na(1.64)Gd(8.36)(SiO(4))(6)O(0.72)F(1.28), Gd(9.34)(SiO(4))(6)O(2),
      Ca(2.6)Eu(7.4)(SiO(4))(6)O(1.4)F(0.6), Ca(4.02)Sm(5.98)(SiO(4))(6)F(2), and
      K(1.32)Pr(8.68)(SiO(4))(6)O(1.36)F(0.64) and powders of NaEu(9)(SiO(4))(6)O(2),
      Na(1.5)Eu(8.5)(SiO(4))(6)OF, Eu(9.34)(SiO(4))(6)O(2), and Gd(9.34)(SiO(4))(6)O(2)
      were synthesized via flux growth in selected alkali-fluoride melts. All of the
      compounds adopt the apatite structure with space group P6(3)/m. Luminescence and
      magnetic data were collected on NaEu(9)(SiO(4))(6)O(2),
      Na(1.5)Eu(8.5)(SiO(4))(6)OF, Eu(9.34)(SiO(4))(6)O(2), and
      Gd(9.34)(SiO(4))(6)O(2). Luminescent data indicate that changing the cations and
      anions that surround the lanthanide site does not change the luminescent
      properties, making apatites versatile structures for optical materials.

PMID- 25372177
TI  - Visceral leishmaniasis in Brazil: rationale and concerns related to reservoir
      control.
AB  - The control of zoonotic visceral leishmaniasis is a challenge, particularly in
      Brazil, where the disease has been gradually spreading across the country over
      the past 30 years. Strategies employed for decreasing the transmission risk are
      based on the control of vector populations and reservoirs; since humans are
      considered unnecessary for the maintenance of transmission. Among the adopted
      strategies in Brazil, the sacrifice of infected dogs is commonly performed and
      has been the most controversial measure. In the present study, we provide the
      rationale for the implementation of different control strategies targeted at
      reservoir populations and highlight the limitations and concerns associated with
      each of these strategies. 

PMID- 25372179
TI  - Assessment of density-functionals for describing the X(-) + CH3ONO2 gas-phase
      reactions with X = F, OH, CH2CN.
AB  - The energetics of the ECO2, SN2@C and SN2@N channels of X(-) + CH3ONO2 (X = F,
      OH, CH2CN) gas-phase reactions were computed using the CCSD(T)/CBS method. This
      benchmark extends a previous study with X = OH [M. A. F. de Souza et al., J. Am.
      Chem. Soc., 2012, 134, 19004] and was used to ascertain the accuracy and
      robustness of nineteen density-functionals for describing these potential energy
      profiles (PEP) as well as the kinetic product distributions obtained from RRKM
      calculations. Assessments were based on the mean unsigned error (MUE), the mean
      signed error (MSE), the #best : #worst (BW) criterion and the statistical
      confidence interval (CI) for the MSE. In general, double-hybrid (DH) functionals
      perform better than the range-separated ones, and both are better than the global
      hybrid functionals. Based on the MUE and CI criteria the B2GPPLYP, B2PLYP, M08
      SO, BMK, omegaB97X-D, CAM-B3LYP, M06, M08-HX, omegaB97X and B97-K functionals
      show the best performance in the description of these PEPs. Within this set, the
      B2GPPLYP functional is the most accurate and robust. The RRKM results indicate
      that the DHs are the best for describing the selectivities of these reactions.
      Compared to CCSD(T), the B2PLYP method has a relative error of only ca. 1% for
      the selectivity and the accuracy to provide the correct conclusion concerning the
      nonstatistical behavior of these reactions. 

PMID- 25372182
TI  - Ruthenium catalyzed hydrogenation of aldehyde with synthesis gas.
AB  - The hydrogenation of aldehyde utilizing synthesis gas as a dihydrogen source was
      examined with various ruthenium catalysts, among which Ru-cyclopentadienone
      complexes (Shvo-type catalysts) exhibited higher activity than others. DFT
      calculations proved that the exchange of coordinated carbon monoxide by
      dihydrogen is relatively preferable in Shvo-type catalysts compared to others,
      which is a pre-equilibrium for the generation of the hydrogenation-active
      species. 

PMID- 25372181
TI  - Patients' experience of identifying and managing exacerbations in COPD: a
      qualitative study.
AB  - BACKGROUND: Effective self-management in chronic obstructive pulmonary disease
      (COPD) is crucial to reduce hospital admissions and improve outcomes for
      patients. This includes early detection and treatment of exacerbations by
      patients themselves. AIMS: To explore patients' current understanding and
      experience of managing and identifying COPD exacerbations at home. METHODS: A
      qualitative, interview-based study was carried out in patients' homes. Interviews
      were audio-recorded, transcribed and analysed using a grounded theory approach.
      Forty-four patients (17 women, 27 men; age range 55-85 years), with moderate-to
      very-severe COPD, were recruited to the interview study from primary and
      secondary care settings in Oxford, UK, during 2012-2013. RESULTS: Patients
      identified exacerbations on the basis of measurable, 'visible' symptoms, such as
      cough and sputum and 'invisible' symptoms, such as chest sensations and bodily
      knowledge. Most patients seemed to use a combination of these approaches when
      identifying exacerbations, according to the symptoms that had the most impact on
      their well-being. Patients used additional self-management strategies during an
      exacerbation, such as self-medication (antibiotics and steroids) and monitored
      their recovery. Contact with health-care professionals usually occurred when
      patients felt no longer able to manage themselves. CONCLUSIONS: Patients use both
      assessment of objective biomarkers, which are aligned with medical knowledge, and
      subjective symptoms based on their experience, to identify and manage
      exacerbations of COPD. Health-care professionals and clinicians should
      acknowledge this 'expert patient' knowledge and integrate this into patients'
      care plans to facilitate early recognition and treatment of exacerbations.

PMID- 25372184
TI  - Limitations of and Barriers to Using Performance Measurement: Purchasers'
      Perspectives.
AB  - Although health plan performance data are becoming increasingly more available,
      many purchasers are still not using these data to make their purchasing
      decisions. In this article, we review barriers that private purchasers face to
      using performance data. In addition, we consider the effects of the larger health
      care purchasing environment and employers' quality improvement activities on
      their use of the data. We conclude that a variety of factors, including trends,
      the health care purchasing environment, characteristics of firms, and problems
      with performance data and their presentation to users create barriers to
      incorporating this information into health care decisionmaking.

PMID- 25372187
TI  - Anorexia nervosa and anorexia mirabilis: Miss K. R--and St Catherine Of Siena.

PMID- 25372183
TI  - Identification of ubiquinol binding motifs at the Qo-site of the cytochrome bc1
      complex.
AB  - Enzymes of the bc1 complex family power the biosphere through their central role
      in respiration and photosynthesis. These enzymes couple the oxidation of quinol
      molecules by cytochrome c to the transfer of protons across the membrane, to
      generate a proton-motive force that drives ATP synthesis. Key for the function of
      the bc1 complex is the initial redox process that involves a bifurcated electron
      transfer in which the two electrons from a quinol substrate are passed to
      different electron acceptors in the bc1 complex. The electron transfer is coupled
      to proton transfer. The overall mechanism of quinol oxidation by the bc1 complex
      is well enough characterized to allow exploration at the atomistic level, but
      details are still highly controversial. The controversy stems from the uncertain
      binding motifs of quinol at the so-called Qo active site of the bc1 complex. Here
      we employ a combination of classical all atom molecular dynamics and quantum
      chemical calculations to reveal the binding modes of quinol at the Qo-site of the
      bc1 complex from Rhodobacter capsulatus. The calculations suggest a novel
      configuration of amino acid residues responsible for quinol binding and support a
      mechanism for proton-coupled electron transfer from quinol to iron-sulfur cluster
      through a bridging hydrogen bond from histidine that stabilizes the reaction
      complex. 

PMID- 25372188
TI  - Junior psychiatrists and independent research.

PMID- 25372189
TI  - Impact of dietary benzoic acid on treatment response in schizophrenia.

PMID- 25372190
TI  - Attention network hypoconnectivity in adults diagnosed as having attention
      deficit/hyperactivity disorder in childhood.

PMID- 25372191
TI  - Impact of dietary benzoic acid on treatment response in schizophrenia--reply.

PMID- 25372192
TI  - Parahippocampal hypoactivation and vulnerability to schizophrenia.

PMID- 25372194
TI  - A purpuric patch on the flank.

PMID- 25372195
TI  - Multimodal retinal imaging in achromatopsia.
AB  - PURPOSE: To investigate comprehensive image findings in a patient with incomplete
      achromatopsia. METHODS: Observational case report. RESULTS: A 12-year-old girl
      was referred to our clinic with nystagmus, photophobia, poor best-corrected
      visual acuity, and impaired color vision since she was 5 years old. Her best
      corrected visual acuity was 20/200 for both eyes. The fundus photography showed
      macula mottling, and fundus autofluorescence imaging showed a bull's eye-like
      maculopathy. The spectral domain optical coherence tomography revealed decreased
      outer nuclear layer thickness and inner and outer segment loss beneath the
      subfoveal area. The electroretinogram showed extinguished cone responses with
      relatively well-preserved rod responses. CONCLUSION: Fundus autofluorescence and
      spectral domain optical coherence tomography may serve as screening tools for
      achromatopsia candidates, but the electroretinogram study remains the most
      reliable test for diagnosis.

PMID- 25372196
TI  - Combined hamartoma of retina and retinal pigment epithelium associated with
      ipsilateral congenital blepharoptosis: a rare association.
AB  - PURPOSE: To report a patient who had concomitant congenital hamartoma of the
      retinal pigment epithelium and retina and ipsilateral congenital blepharoptosis.
      METHODS: Case report. RESULTS: An 11-year-old male presented with left-sided
      congenital blepharoptosis and combined hamartoma of the retina and retinal
      pigment epithelium in the ipsilateral eye. The systemic examination was within
      normal limits. The diagnosis of combined hamartoma was established by typical
      ophthalmoscopic and optical coherence tomography findings. CONCLUSION: Congenital
      blepharoptosis may be associated with ipsilateral combined hamartoma of the
      retina and retinal pigment epithelium.

PMID- 25372197
TI  - Endogenous Serratia marcescens endophthalmitis.
AB  - PURPOSE: The purpose of this study was to describe a rare case of endogenous
      endophthalmitis associated with dental disease secondary to Serratia marcescens
      in an HIV-negative individual. METHODS: Retrospective case report. RESULTS: A 50
      year-old white man with a history of intravenous drug use presented with pain and
      decreased vision in his right eye. Slit-lamp examination showed a hazy cornea,
      hypopyon with fibrin in the anterior chamber, and elevated intraocular pressure.
      B-scan ultrasound showed vitritis and choroidal thickening. Computed tomography
      showed gingival inflammation and lucencies of several teeth. Blood and urine
      cultures were negative, and HIV testing was negative. Echocardiography was
      negative for vegetations. Intravitreal culture revealed S. marcescens. Despite
      intravitreal and systemic antibiotics, the patient's clinical situation rapidly
      deteriorated, and the eye was eviscerated. The patient underwent dental
      extraction and was subsequently discharged in stable condition. CONCLUSION: The
      first case of endogenous endophthalmitis secondary to S. marcescens in an
      otherwise healthy, HIV-negative, intravenous drug user in association with severe
      dental disease is reported. Serratia may be found in oral biofilm, and this
      mechanism should be considered in cases where other etiologies have been ruled
      out.

PMID- 25372198
TI  - Fiberglass intraocular foreign body with no initial ocular symptoms.
AB  - PURPOSE: To report a case of an occult intraocular foreign body missed on initial
      presentation. To our knowledge, this is the first reported case of fiberglass as
      an intraocular foreign body. METHODS: A case report in which the clinical
      presentation of the patient was documented by color anterior segment and fundus
      photographs, optical coherence tomography (OCT), and computed topography (CT) of
      the orbit. RESULTS: A 34-year-old male was referred for the evaluation of an
      acute unilateral preretinal hemorrhage of undetermined origin. Three months
      before his presentation, he had a foreign body sensation while cutting
      fiberglass, which lasted for several hours. He denied having any visual
      complaints until his presentation 3 months later. On anterior examination, a
      small paracentral corneal scar was noticed. There was no cell or flare. A small
      iris defect inferior nasal with an adjacent area of broad based peripheral
      anterior synechia on gonioscopy was noted. On funduscopy, a large subretinal
      elevation with an underlying hemorrhage adjacent to the disk with a white foreign
      body partially imbedded in the retina was seen. A vitreous hemorrhage was
      overlying the macula. Because there were no signs of infection or inflammation,
      surgical intervention was avoided. Barrier laser was performed around the
      subretinal elevation. CONCLUSION: Occurrence of intraocular foreign bodies,
      although not uncommon, has a varying presentation. Most often devastating and
      dramatic, clinical signs may not be obvious or appreciated on thorough
      examination, especially when the offending object is very small. Intraocular
      foreign bodies composed of inert material (i.e., glass/fiberglass) can leave the
      eye without inflammation, further making the diagnosis difficult.

PMID- 25372199
TI  - Management of refractory Leber miliary aneurysms with macular edema: a case
      report.
AB  - PURPOSE: To report a case study of a patient with Leber miliary aneurysms with
      macular edema refractory to various treatment modalities. METHODS: This is a
      retrospective study of a 35-year-old man who had multiple Leber miliary aneurysms
      with exudation and edema involving the macula. The patient's data were collected
      from case notes over a 3-year period of management of the condition. RESULTS: The
      patient's Leber miliary aneurysm with exudation and macular edema was refractory
      to various treatment modalities, including laser photocoagulation, anti-vascular
      endothelial growth factor injections, photodynamic therapy, and cryotherapy.
      However, recently, the patient showed a good response to treatment with
      intravitreal dexamethasone implants. His macular edema and vision have improved
      with these injections. CONCLUSION: Intravitreal dexamethasone implants should be
      considered along with other treatment options when planning treatment of Leber
      miliary aneurysms. However, the long-term stability of the disease with these
      injections is not known.

PMID- 25372200
TI  - Retinal involvement in uveitis associated with Hodgkin disease.
AB  - PURPOSE: To describe a patient with Hodgkin disease with posterior uveitis who
      also had a thinning of the retina and an antiretinal autoantibody in his serum.
      METHODS: Our patient was a 58-year-old man who had been diagnosed with Hodgkin
      disease. He had a complete ophthalmologic examination including fluorescein
      angiography, electroretinography, perimetry, and spectral-domain optical
      coherence tomography. A search for antiretinal antibodies in the serum was made
      by Western blot analysis, and the retinal sites reactive to the antibodies were
      determined by immunohistochemistry. RESULTS: The ocular signs were mild cellular
      infiltration in the anterior chamber and vitreous, and small, round chorioretinal
      lesions in the peripheral retina. The electroretinograms were slightly reduced.
      Small ring-like scotomas were detected in the Goldmann visual fields. An
      antiretina-specific 116-kDa antibody was detected in the serum by Western blot
      analysis, and the antibody reacted with the ganglion cell and inner nuclear
      layers of mice retinas. Although the visual acuities were maintained for over
      eight years, the macular thickness measured in the spectral-domain optical
      coherence tomography images was reduced. CONCLUSION: The presence of an
      antiretinal autoantibody, granulomatous uveitis, and retinal thinning in a
      patient with Hodgkin disease suggests that the patient had a granulomatous
      uveitis associated with Hodgkin disease or lymphoma-associated uveitis with
      retinal involvement.

PMID- 25372201
TI  - An ischemic diabetic eye treated with intravenous prostaglandin E1.
AB  - PURPOSE: To present the use of intravenous prostaglandin E1 (PGE1), a powerful
      vasodilator of the microcirculation, in the treatment of an ischemic diabetic
      eye. METHODS: A 27-year-old diabetic man with ischemic diabetic retinopathy and
      glaucoma had a decreased visual acuity of no light perception in his right eye
      and hand motions in his left eye. He was started on intravenous PGE1 and has been
      treated for over 4.5 years. RESULTS: The visual acuity in his right eye remained
      unchanged and in his left eye improved gradually to 1.5/30. He has been stable
      for 4.5 years. CONCLUSION: Intravenous PGE1 may be useful in ischemic diabetic
      eyes to improve the ocular blood flow and visual acuity. It is safe and tolerated
      well.

PMID- 25372202
TI  - Intravitreal anti-vascular endothelial growth factor for choroidal
      neovascularization in ocular histoplasmosis.
AB  - PURPOSE: To report eight cases of long-term successful treatment of choroidal
      neovascularization because of ocular histoplasmosis syndrome with intravitreal
      anti-vascular endothelial growth factor agents. METHODS: Retrospective case
      series. This article reviewed the course of eight eyes in seven patients who
      underwent intravitreal injection of bevacizumab and/or ranibizumab for treatment
      of choroidal neovascularization secondary to ocular histoplasmosis syndrome.
      Outcomes were assessed using pre- and post-anti-vascular endothelial growth
      factor visual acuities. RESULTS: Eight eyes in seven patients were found to have
      new ocular histoplasmosis syndrome-associated subfoveal choroidal
      neovascularization lesions, as evidenced on clinical examination, fluorescein
      angiography, and optical coherence tomography. Intravitreal anti-vascular
      endothelial growth factor injections were used as initial or early treatment with
      successful resolution of the choroidal neovascularization lesions in most cases.
      Mean visual acuity improved from 20/60 to 20/47 over an average of 121.4 weeks.
      Either bevacizumab or ranibizumab was administered with an average of 2.6
      injections per year of follow-up. Three eyes (37.5%) experienced a gain in visual
      acuity with a mean increase of 7.7 lines, 1 eye (12.5%) experienced no change,
      and 2 eyes (25%) experienced a loss of visual acuity of 2 or more lines. Six eyes
      (75%) were able to avoid mild visual loss (2 lines or less). CONCLUSIONS:
      Intravitreal anti-vascular endothelial growth factor agents may successfully
      treat or at least stabilize neovascular complications of ocular histoplasmosis
      syndrome when used as a first-line treatment.

PMID- 25372203
TI  - Late reopening of an initially successfully closed macular hole after 12 years.
AB  - PURPOSE: An uncommon late complication after successful initial surgical closure
      of a full-thickness macular hole is reopening. METHODS: A retrospective
      interventional case report. RESULTS: A 58-year-old pseudophakic woman presented
      with 6 weeks of decreased vision in her right eye. She was found to have a full
      thickness macular hole, which was successfully repaired through pars plana
      vitrectomy, epiretinal membrane peeling, gas-fluid exchange with 25% SF6, and 7
      days of face-down positioning. Twelve years later, she presented with new
      metamorphopsia and visual acuity of 20/50 in the right eye. Examination revealed
      reopening of the macular hole. CONCLUSION: Despite high rates of surgical
      success, the reopening of initially closed macular holes can occur at any time
      postoperatively but has been reported more frequently in the first few months,
      though late reopenings have been observed. This is the latest reopening of a
      macular hole reported in the literature, occurring 12 years after initial
      successful surgical closure. This case highlights the importance of long-term
      follow-up and raises questions about why macular holes can reopen so late after
      initial successful closure.

PMID- 25372204
TI  - External subretinal drainage, bevacizumab, and scleral buckling for complete
      exudative retinal detachment after photocoagulation in retinopathy of
      prematurity.
AB  - BACKGROUND: Total serous retinal detachment after laser photocoagulation for
      retinopathy of prematurity is an infrequent type of retinal detachment in preterm
      babies. PURPOSE: To describe the successful outcome for treatment by scleral
      drainage, bevacizumab, and scleral buckling for complete serous exudative retinal
      detachment in a patient with retinopathy of prematurity. METHODS: A preterm baby
      with primary pulmonary hypertension under treatment with sildenafil developed a
      total (retrolental) serous retinal detachment after photocoagulation for
      threshold retinopathy. The dense subretinal fluid was externally drained using a
      bent needle with an infusion placed in the anterior chamber. Additional
      bevacizumab and scleral buckling helped to control the plus disease and
      subretinal leakage. RESULTS: Retinal apposition was obtained with the described
      approach. CONCLUSION: Total serous retinal detachment is a rare but severe visual
      complication in retinopathy of prematurity. The described technique may restore
      the retinae immediately in a visually critical period.

PMID- 25372205
TI  - Successful treatment of choroidal neovascularization secondary to persistent
      placoid maculopathy with intravitreal bevacizumab.
AB  - PURPOSE: To report a case of posterior placoid maculopathy with secondary
      choroidal neovascularization that responded favorably to repeat intravitreal
      injections of bevacizumab with long-term follow-up. METHODS: Patient data from
      all clinic visits were reviewed. These include visual acuity measurements and
      clinical examination findings, optical coherence tomography, color fundus
      photography, and fluorescein angiography images from the initial visit and follow
      up encounters. RESULTS: This patient showed clear evidence of active leakage from
      choroidal neovascularization on presentation that promptly resolved with
      treatment. After his initial course of injections, all evidence of active
      exudation disappeared from his optical coherence tomography scans. However, when
      treatment was extended beyond 8 weeks, choroidal neovascularization leakage
      returned. In addition, the patient developed subretinal fibrosis in one eye
      despite regular treatments. Nevertheless, visual acuity has remained excellent
      through his most recent encounter. CONCLUSION: Persistent placoid maculopathy is
      an exceedingly rare clinical entity. In their original descriptive series,
      Golchet et al revealed that 9 of the 12 eyes went on to develop poor vision from
      complications of choroidal neovascularization. There is currently only one case
      in the literature that describes the use of anti-vascular endothelial growth
      factor medications in the treatment of persistent placoid maculopathy with
      promising results. This case adds supporting evidence for this treatment modality
      and highlights the need for continued follow-up and treatment till 18 months from
      presentation.

PMID- 25372206
TI  - Staphylococcus lugdunensis endophthalmitis after intravitreal injection: a case
      series.
AB  - PURPOSE: To report the clinical features and visual and anatomical outcomes in
      three patients with Staphylococcus lugdunensis endophthalmitis after intravitreal
      injection. METHODS: This study was a retrospective, interventional case series
      conducted at a single, tertiary care retina referral practice under the approval
      of Western Institutional Review Board. Records of three eyes with culture
      positive S. lugdunensis endophthalmitis after intravitreal injection with
      Lucentis or Avastin were reviewed. All patients were treated between November
      2011 and March 2012. RESULTS: All three patients developed symptoms of
      endophthalmitis 2 to 3 days after intravitreal injection and were culture
      positive for S. lugdunensis. Initial visual acuity ranged from 20/200 to light
      perception. Final visual acuity ranged from 20/100 to hand motion. Duration of
      follow-up ranged from 4 months to 10 months. One patient was treated with
      vitreous tap and injection of ceftazidime and vancomycin. Two patients underwent
      immediate vitrectomy and injection of intravitreal ceftazidime and vancomycin.
      One patient developed a retinal detachment requiring pars plana vitrectomy and
      silicone oil. All three patients demonstrated an early and aggressive course.
      CONCLUSION: This case series demonstrates that S. lugdunensis endophthalmitis can
      follow an aggressive course atypical for coagulase-negative organisms. Accurate
      identification of S. lugdunensis is important for management and prognosis.
      However, identification of S. lugdunensis is confounded by potential false
      positive coagulase tests and the lack of routine speciation by microbiology
      laboratories.

PMID- 25372207
TI  - Dark adaptation abnormalities and recovery in acute thioridazine toxicity.
AB  - PUPOSE: To document acute thioridazine toxicity from the symptoms only, through
      the development of ophthalmoscopic signs and recovery of dark adaptation and
      electroretinogram responses. These findings support the thesis that visual loss
      is metabolic and reversible if diagnosed early. METHODS: Case Report. RESULTS: A
      case is presented of acute thioridazine toxicity with documentation of the
      development of symptoms before any ophthalmoscopic evidence of toxicity. This
      case uniquely shows the time course of dark adaptation, showing both delay in
      adaptation and elevated final threshold, it includes full electrophysiologic
      studies from within the first weeks of symptoms and regular follow-up
      demonstrating marked recovery of dark adaptation in terms of both delay and final
      threshold, a nearly normal electroretinography and normal color vision within 10
      months. CONCLUSION: Our findings give support to the thesis that functional
      visual disturbance is primarily metabolic and reversible if detected early in the
      course of toxicity.

PMID- 25372208
TI  - Cytomegalovirus retinitis: an unusual presentation as vitreous hemorrhage.
AB  - PURPOSE: The purpose of this report is to describe an unusual presentation of
      vitreous hemorrhage (VH) in a patient with an immunosuppressive condition.
      METHODS: Retrospective case report. RESULTS: A 72-year-old woman with known T
      cell prolymphocytic leukemia treated with a course of alemtuzumab presented to
      our department with a VH in her left eye after a fall. An initial diagnosis of
      hemorrhagic posterior vitreous detachment was made. However, as the VH was
      resolving, she was found to have underlying vitritis, occlusive vasculitis, and a
      pale optic nerve head. Vitreous biopsy confirmed cytomegalovirus retinitis.
      Despite treatment with intravenous foscarnet and oral valganciclovir, her vision
      continued to remain poor because of the severe damage from the retinal vasculitis
      and residual VH. CONCLUSION: As indications for immunosuppression increase, the
      incidence of cytomegalovirus retinitis in non-HIV-immunosuppressed patients is
      expected to rise. Therefore, in this subgroup of patients, we should be aware of
      any underlying retinitis especially in cases with an unusual presentation of VH.

PMID- 25372209
TI  - Choroidal thinning and "stair-case" foveal sign in a patient with Alport
      syndrome.
AB  - PURPOSE: To quantitatively describe choroidal thickness in a patient with Alport
      syndrome and to qualitatively describe an unusual "stair-case" foveal sign.
      METHODS: Retrospective case report. RESULTS: This is the first case, to our
      knowledge, of the stair-case foveal sign. This is also the first case where
      choroidal thickness in a patient with Alport rsyndrome has been quantitatively
      described using enhanced depth imaging optical coherence tomography. CONCLUSION:
      Stair-case foveal sign and choroidal thinning are two new signs that clinicians
      can expect to encounter on optical coherence tomography imaging of patients with
      Alport syndrome.

PMID- 25372210
TI  - Infantile Refsum disease in a young adult: case presentation and brief review.
AB  - PURPOSE: To review and describe findings, pathophysiology, and management of
      infantile Refsum disease in a young adult, and to compare with those of classic
      Refsum Disease. METHODS: Retrospective chart and digital photography review.
      RESULTS: A 25-year-old woman with a diagnosis of infantile Refsum disease
      presented with progressively decreasing vision. Findings included a
      noncorpuscular pigmentary degeneration of both fundi, optic nerve head drusen,
      attenuated retinal vasculature, cataract, myopia, and esotropia. She was treated
      with a low phytanic acid diet, resulting in improved metabolic values on
      laboratory testing. CONCLUSION: Infantile Refsum disease has clinical features
      and a pathophysiology distinct from classic Refsum disease, despite occasionally
      presenting for examination later in life. Ophthalmic and systemic distinctions
      between the two are important to consider for the ophthalmologist, who may be
      involved in the initial diagnosis of the patient.

PMID- 25372211
TI  - Retinal blood flow levels measured by laser speckle flowgraphy in patients who
      received intravitreal bevacizumab injection for macular edema secondary to
      central retinal vein occlusion.
AB  - PURPOSE: To report retinal blood flow levels measured by Laser speckle flowgraphy
      in three patients after they received an intravitreal bevacizumab injection (IVB)
      for macular edema secondary to central retinal vein occlusion (CRVO). METHODS:
      Three patients (3 eyes) being treated with IVB (1.25 mg/0.05 mL) for secondary
      macular edema of CRVO were examined. Laser speckle flowgraphy analyses of the
      blood flow were based on the examinations of mean blur rate (MBR) at the major
      vessels of the optic disk. Central retinal thickness (CRT) was measured by
      optical coherence tomography using Macular Cube 512 * 128 scanning protocol.
      RESULTS: After the first IVB, Case 1 exhibited an increase in MBR and decrease in
      CRT. After 4 months, an additional injection was required because of a subsequent
      MBR decrease and CRT increase, which led to an increase in MBR and decrease in
      CRT similar to that observed after the first treatment. Subsequently, blood flow
      has continued to improve without additional IVB. Macular edema recurrence in Case
      2 led to 3 further IVBs over a 6-month period. Although increases in MBR and
      decreases in CRT were noted, MBR values tended to decline after each IVB. In Case
      3, macular edema recurrence led to 5 additional IVBs being carried out within a 1
      year period. Continuous MBR increases and CRT decreases were observed in the
      patient after each IVB. By measuring MBR using laser speckle flowgraphy, we may
      predict the prognosis of CRVO. CONCLUSION: Mean blur rate increases after IVB
      were confirmed by laser speckle flowgraphy in three patients. Even though CRVO
      pathology backgrounds can vary, laser speckle flowgraphy may be useful in both
      determining the CRVO prognosis and in evaluating treatment efficacy.

PMID- 25372212
TI  - Hydroxychloroquine retinopathy after short-term therapy.
AB  - PURPOSE: To report an unusual case of hydroxychloroquine toxicity after short
      term therapy. METHODS: Observational case report. RESULTS: A 56-year-old woman
      presented to the Ophthalmology Clinic at Walter Reed Army Medical Center (WRAMC)
      with a 6-month history of gradually decreasing vision in both eyes. The patient
      had been taking hydroxychloroquine for the preceding 48 months for the treatment
      of rheumatoid arthritis. Examination of the posterior segment revealed bilateral
      "bull's eye" macular lesions. Fundus autofluorescence revealed hyperfluorescence
      of well-defined bull's eye lesions in both eyes. Optical coherence tomography
      revealed corresponding parafoveal atrophy with a loss of the retinal inner
      segment/outer segment junction. Humphrey visual field 10-2 white showed
      significant central and paracentral defects with a generalized depression. The
      patient was on a standard dose of 400 mg daily, which was above her ideal dose.
      The patient had no history of kidney or liver dysfunction. There were no known
      risk factors but there were several possible confounding factors. The patient was
      started on high-dose nabumetone, a nonsteroidal antiinflammatory drug, at the
      same time she was started on hydroxychloroquine. She also reported taking
      occasional ibuprofen. CONCLUSION: Retinal toxicity from chloroquine has been
      recognized for decades with later reports showing retinopathy from long-term
      hydroxychloroquine (Plaquenil) use for the treatment of antiinflammatory
      diseases. Hydroxychloroquine is now widely used and retinal toxicity is
      relatively uncommon. However, it can cause serious vision loss and is usually
      irreversible. The risk of hydroxychloroquine toxicity rises to nearly 1% with a
      total cumulative dose of 1,000 g, which is ~5 years to 7 years of normal use.
      Toxicity is rare under this dose. For this reason, the American Academy of
      Ophthalmology has revised its recommendations such that annual screenings begin 5
      years after therapy with hydroxychloroquine has begun unless there are known risk
      factors. This case report confirms the need for a baseline examination and annual
      ophthalmologic screening for patients taking hydroxychloroquine at a dose higher
      than the recommended dosage. It is also reasonable to consider annual
      examinations in patients taking high-dose nonsteroidal antiinflammatory drugs
      from the initiation of the medication.

PMID- 25372213
TI  - Rifampin induced hepatotoxicity during treatment for chronic central serous
      chorioretinopathy.
AB  - PURPOSE: The purpose of this report is to present a case of hepatotoxicity
      secondary to off-label rifampin therapy for the treatment of chronic central
      serous choroidopathy. METHODS: Case report. RESULTS: A patient with chronic
      central serous chorioretinopathy was treated with oral rifampin. Three weeks
      after the initiation of therapy, fatigue, nausea, and malaise associated with
      elevated liver enzyme elevations were noted. Symptoms resolved and liver enzymes
      normalized after discontinuing rifampin. CONCLUSION: Rifampin-induced hepatic
      injury can occur during therapy for chronic central serous chorioretinopathy.
      Potential hepatotoxicity must be considered and followed closely during off-label
      rifampin treatment.

PMID- 25372214
TI  - Optic neuropathy associated with copper deficiency after gastric bypass surgery.
AB  - PURPOSE: Patients undergoing gastric bypass procedures are predisposed to many
      vitamin and mineral deficiencies including copper, which can lead to optic
      neuropathy. METHODS: A 35-year-old woman complained of progressive vision loss
      bilaterally 3 years after gastric bypass surgery (GBS). RESULTS: Ophthalmic
      examination revealed the presence of subnormal visual acuity and pale optic
      nerves bilaterally. Laboratory testing showed copper deficiency. Complete
      improvement in vision was noted after copper was replenished. CONCLUSION:
      Nutritional deficiencies occurring after gastric bypass procedures are well
      reported. They happen and occur due to reduced gastric and enteral absorption and
      cause many systemic and neurologic manifestations. Optic neuropathy occurring
      after GBS is often due to vitamin B12 and folic acid deficiency. Copper
      deficiency causing systemic symptoms is very rare and usually takes decades to
      manifest. Our case is unique in that copper deficiency was noted as early as 3
      years after GBS. Moreover rapid copper replenishment led to a dramatic recovery
      of vision. Our case underscores the need for maintaining high suspicion when
      evaluating patients with suspected optic neuropathy occurring after GBS since
      prompt diagnosis and treatment may lead to reversal of visual loss.

PMID- 25372215
TI  - Retinal vasculature remodeling in a case of systemic lupus erythematosus vaso
      occlusive retinopathy.
AB  - PURPOSE: To report a case of systemic lupus erythematosus vaso-occlusive
      retinopathy illustrating vascular remodeling over 4 years of follow-up. METHODS:
      Observational case report of one patient. RESULTS: A 12-year-old previously
      healthy girl presented with profound vision loss to 20/800 in both eyes. Her
      medical workup, neuro-imaging, and ophthalmic examination were consistent with
      coexistent central nervous system systemic lupus erythematosus and vaso-occlusive
      systemic lupus erythematosus retinopathy. At 15 months after presentation,
      retinal vasculature remodeling was evident along with severe macular atrophy. By
      4 years after presentation, retinal neovascularization developed that was
      successfully treated with photocoagulation. CONCLUSION: We describe a case of
      systemic lupus erythematosus vaso-occlusive retinopathy illustrating vascular
      remodeling over 4 years of follow-up.

PMID- 25372216
TI  - Subretinal peripapillary neovascularization associated with persistent fetal
      vasculature.
AB  - PURPOSE: The purpose of this study was to report a unique case of persistent
      fetal vasculature presenting as peripapillary choroidal neovascularization.
      METHODS: Ophthalmologic examination, examination under anesthesia, fluorescein
      angiogram, chart review, review of relevant literature. A 2-year 4-month-old
      white girl was referred for decreased vision and suspicious retinal findings.
      RESULTS: Fundus examination of the right eye demonstrated a peripapillary macular
      scar with old subretinal hemorrhage, subretinal fluid consistent with
      peripapillary neovascular net, a persistent fetal vascular stalk, and a central
      posterior lenticular opacity. Fluorescein angiogram of the right eye showed
      normal arterial filling in the early phase, normal arteriovenous transit, and
      late staining with mild leakage. CONCLUSION: This is a unique case of persistent
      fetal vasculature presenting with the findings of subretinal exudates and
      choroidal neovascularization that has not been described before. Although the
      etiology of the choroidal neovascularization is unclear, we postulate it may be a
      result of the traction from the persistent fetal vasculature stalk in the
      peripapillary region. These findings may also be secondary to an optic disk
      anomaly that was not detected on examination.

PMID- 25372218
TI  - Rotating crystals of magnetic Janus colloids.
AB  - Monodisperse magnetic colloids are found to self-assemble into unusual crystals
      in the presence of rotating magnetic fields. First, we confirm a predicted phase
      transition (S. Jager and S. H. L. Klapp, Soft Matter, 2011, 7, 6606-6616),
      directly coupled to the dynamic transition of single particle motion, from a
      disordered state to a hexagonal crystal. Next, going beyond what had been
      predicted, we report how hydrodynamic coupling produces shear melting,
      dislocations, and periodically mobile domain boundaries. These uniform magnetic
      colloids, whose structures are modulated in situ using the protocols described
      here, demonstrate a strategy of stimulus-response in the colloid domain with
      potential applications. 

PMID- 25372219
TI  - Low intensity laser for reducing pain from anesthetic palatal injection.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of pain
      reduction techniques for palatal injection, namely, low intensity laser therapy
      (LILT), topical anesthesia, pressure, and light touch. BACKGROUND DATA: Previous
      evidence indicates that LILT may prevent pain from palatal injection. However, no
      clinical trials evaluating this clinical question have been performed. METHODS: A
      double-blind clinical trial was conducted using 80 healthy volunteers, 18-25
      years of age. The subjects were randomly allocated into four groups with 10
      females and 10 males each group. Pain reduction techniques were administered at
      an injection point that was 10 mm from the margin of the palatal gingiva of the
      upper left first molar according to the following groups: (1) a 790 nm 30 mW
      continuous wave with a 0.13 cm2 focal spot at an applied energy of 3.6 J and
      fluence of 27.69 J/cm2, (2) 20% benzocaine, (3) pressure, and (4) light touch as
      the control. Then, 2% lidocaine with 1:100,000 epinephrine was injected using a
      27-gauge needle with a pressure and volume control intraligamentary syringe. All
      subjects recorded pain on a 10 cm visual analog scale (VAS). RESULTS: The pain
      score in the LILT group was <50 mm. The median of pain scores of the LILT, 20%
      benzocaine, pressure, and light touch groups were 11, 23, 27, and 31 mm,
      respectively. There was no statistically significant difference in VAS among the
      groups, using Kruskal-Wallis test (p=0.385). CONCLUSIONS: No statistically
      significant differences in pain scores were noted among low intensity laser, 20%
      benzocaine, pressure, and light touch.

PMID- 25372221
TI  - Overview.
AB  - This overview discusses articles published in this special 30th Anniversary of
      Medicare issue of the Health Care Financing Review. The authors whose work
      appears in this special commemorative issue all participated in a policy
      symposium held on May 6, 1996, at the Lyndon B. Johnson Library in Austin, Texas.
      The symposium, Medicare: Advancing Towards the 21st Century, was held in honor of
      the 30th anniversary of the implementation of the Medicare program. Co-sponsors
      of the symposium included the Health Care Financing Administration, the Lyndon B.
      Johnson Library, the Lyndon B. Johnson School of Public Affairs at the University
      of Texas at Austin, the Commonwealth Fund, the Robert Wood Johnson Foundation,
      and the Henry J. Kaiser Family Foundation.

PMID- 25372220
TI  - Statistical assessment of biosimilarity based on the relative distance between
      follow-on biologics for binary endpoints.
AB  - A new three-arm parallel design was recently proposed to investigate the
      biosimilarity between a biological product and a reference product by using the
      relative distance. The purpose of this article is to extend their results to
      binary endpoints for three popular metrics: the risk difference, the log relative
      risk, and the log odds ratio. The relative distances based on the three metrics
      are defined, and corresponding test procedures are developed. The type I error
      rates and powers are investigated theoretically and empirically. 

PMID- 25372223
TI  - Trends in Medicare Expenditures and Financial Status, 1966-2000.
AB  - In this article, the author reviews expenditure growth trends over Medicare's 35
      year history and comments on how the program's long-range financial outlook has
      changed over time. The author focuses on the various legislative, economic, and
      demographic factors that have affected expenditure growth and financial status.
      In addition, Medicare's share of total U.S. health costs is briefly reviewed. In
      an appended comment, the author considers whether the impact of the Balanced
      Budget Act of 1997 (BBA) was greater than intended by Congress and the
      Administration. The author concludes with a plea for greater attention to
      correcting the projected long-range deficits for the Hospital Insurance (HI)
      Trust Fund.

PMID- 25372224
TI  - Health Care Indicators.
AB  - THIS REGULAR FEATURE OF THE JOURNAL INCLUDES A DISCUSSION OF EACH OF THE
      FOLLOWING FOUR TOPICS: community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25372225
TI  - Secular trends in invasive meningococcal disease, Massachusetts, 1988-2011: what
      happened to invasive disease?
AB  - Invasive meningococcal disease (IMD) reported to the Massachusetts Department of
      Public Health from 1988 to 2011 was reviewed. The average annual incidence of
      IMD/100 000 decreased from 1.57 [95% confidence interval (CI) 1.42-1.73] for 1988
      1991 to 0.22 (95% CI 0.17-0.29) for 2008-2011. The pattern of decreasing
      incidence over time differed by age group. There was a decrease in IMD/100 000 in
      the 0-4 years age group after 1991 from 10.92 (95% CI 8.08-14.70) in 1991 to 5.76
      (95% CI 3.78-8.72) in 1992. Incidence in the 0-4 years age group remained below
      5/100 000 per year on average thereafter. A substantial reduction in incidence in
      all age groups was observed between 2000 and 2009, which began before the
      introduction of conjugate meningococcal vaccine in 2005. Marked reductions in
      incidence of IMD in Massachusetts, and elsewhere, deserve further investigation
      with respect to potential factors that go beyond the introduction and deployment
      of improved meningococcal vaccines.

PMID- 25372226
TI  - Potential effect of virus interference on influenza vaccine effectiveness
      estimates in test-negative designs.
AB  - A hypothetical influenza infection-induced non-specific immunity may reduce the
      risk of subsequent non-influenza respiratory virus (NIRV) infection and bias the
      influenza vaccine effectiveness (VE) estimates in test-negative designs (TNDs).
      We conducted a simulation study using a simple TND model and explored the degree
      of bias in the VE estimates. The bias was marginal during the usual seasons and
      most of the time during pandemics; the bias only became large when the influenza
      infection attack rate increased to pandemic levels (>50%), the true VE was low to
      moderate, and the non-specific immunity almost completely protected from NIRV
      infections and lasted at least half the influenza season.

PMID- 25372227
TI  - Retrospective epidemiological analysis of sparganosis in mainland China from 1959
      to 2012.
AB  - In this study, epidemiological factors of sparganosis cases reported in mainland
      China from 1959 to December 2012 were analysed. A total of 1061 valid cases were
      distributed throughout most of the provinces of mainland China, with most cases
      occurring in Southern and Eastern China. The average age of patients was 29 years
      (range 0-80 years). Modes of transmission to humans were via contact (54.6%),
      mainly by application of frog meat as a poultice, foodborne (33.8%), mainly
      through ingesting frogs or snakes, and waterborne (11.5%) through drinking raw
      water. The tissue/organs involved were subcutaneous/muscle (43.1%), eyes (31.0%),
      central nervous system (CNS) (17.9%), urogenital system (3.9%) and visceral
      organs (3.2%). Obvious differences existed in main risk factors for different
      areas. Close correlation was found between tissue/organs and risk factors. Main
      modes of transmission changed during the past decades, from contact (83.8% pre
      1979) to foodborne (63.9% post-2000). The tissue/organs involved also changed at
      the same time. Cases involving eyes fell from 50.0% pre-1979 to 8.3% post-2000,
      and cases involving CNS increased from 0% pre-1979 to 47.8% post-2000. These
      results illustrate that China is one of the main epidemic countries of
      sparganosis in the world. Consumption of frog/snake meat was the main risk
      factor, although application of frog flesh as a poultice was the main risk factor
      before 2000. Sparganosis has become one of the neglected but important
      foodborne/waterborne parasitic diseases in mainland China.

PMID- 25372228
TI  - Impact of vanB vancomycin-resistant enterococcal bacteraemia analysed as a time
      varying covariate on length of hospital stay.
AB  - The impact of vanB vancomycin-resistant enterococci (VRE) bacteraemia on length
      of stay (LOS) in hospital, after adjusting for the time-varying nature of
      enterococcal bacteraemia (variable onset of bacteraemia post-admission), is
      unknown. Survival analyses (time-varying Cox and competing risks regression) were
      performed on vanB VRE bacteraemia patients, matched 1:1 with vancomycin
      susceptible enterococci bacteraemia patients to determine the factors associated
      with LOS in these patients. In Cox regression analysis, vanB VRE bacteraemia,
      intensive-care-unit admission, Charlson co-morbidity index score ?4, and an
      increase in the time to receive appropriate antibiotics were associated with
      prolonged LOS. Competing risks regression which accounts for the influence of in
      patient mortality on the ability to observe the event discharge alive from
      hospital suggests that, vanB VRE bacteraemia was not significantly associated
      with prolonged LOS. For the first time, the rate of discharge from hospital in
      patients with vanB VRE bacteraemia has been quantified.

PMID- 25372229
TI  - Medicaid and the HIV/AIDS Epidemic in the United States.
AB  - This article explores the impact on Medicaid costs of new AIDS treatments and
      other technology advances. Available data on total projected Medicaid
      expenditures and actual expenditures for antiretroviral drugs are presented. The
      article further addresses Medicaid State agencies' efforts to assure that
      Medicaid-eligible persons with AIDS receive quality care, and reviews recent
      studies on utilization of services among persons with HIV disease.

PMID- 25372230
TI  - Associations Between Extracurricular Activity and Self-Regulation: A Longitudinal
      Study From 5 to 10 Years of Age.
AB  - PURPOSE: Health promotion in youth is likely to benefit from enhancing academic
      achievement and physical activity. The present study examines how kindergarten
      childhood self-regulation skills and behaviors predict involvement in both
      structured and unstructured physical and nonphysical extracurricular activities
      in the fourth grade. As a second objective this study also investigated how
      kindergarten childhood participation in extracurricular activities predicts
      classroom engagement, reflective of self-regulation, by the fourth grade. DESIGN:
      Secondary analyses were conducted using prospective-longitudinal data. SETTING:
      The Quebec Longitudinal Study of Child Development, Quebec, Canada. SUBJECTS:
      Participants were randomly selected at birth from a stratified sample of 2694
      born in Quebec, Canada, between 1997 and 1998. Participants were included if they
      had complete data on teacher ratings of child self-regulation as measured by
      classroom engagement and parent ratings of sports participation (n = 935).
      MEASURES: Teachers reported self-regulation skills in children through a measure
      of classroom engagement. Parents provided reports of child participation
      extracurricular activities. ANALYSIS: Ordinary least-squares regressions were
      conducted. RESULTS: A higher-frequency kindergarten involvement with structured
      physical activities was associated with fourth-grade classroom engagement (beta =
      .061, 95% confidence interval [CI]: .017, .104). Better kindergarten classroom
      engagement predicted more frequent participation in fourth-grade structured
      physical activities (beta = .799, 95% CI: .405, 1.192) and team sports (beta =
      .408, 95% CI: .207, .608). CONCLUSION: Results suggest mutual relations between
      physical activity and self-regulation from kindergarten to grade four. This
      suggests strong learning skills indicative of self-regulation and opportunities
      to participate in supervised physical activities or sports teams may help
      children develop healthy dispositions and behaviors in emerging adolescence.

PMID- 25372231
TI  - Predictors for Persistent Overweight, Deteriorated Weight Status, and Improved
      Weight Status During 18 Months in a School-Based Longitudinal Cohort.
AB  - PURPOSE: To examine predictors for persistent overweight/obesity, deteriorated
      weight status, and improved weight status among students who participated in a
      school-based obesity prevention intervention from fall 2009 to spring 2011.
      DESIGN: Longitudinal assessment of a school-based cohort was conducted to
      determine the characteristics of students who remained overweight/obese, improved
      their weight status, or showed deteriorated weight status during an 18-month
      period. SETTING: Eleven schools in southern Indiana, northwestern Kentucky, and
      southeastern Illinois. SUBJECTS: N = 5309 students in 4th through 12th grade.
      MEASURES: Weight, height, and self-reported physical activity and nutrition
      behaviors of students were measured at baseline and 6, 12, and 18 months.
      ANALYSIS: SAS 9.3 was employed to examine predictors for the three different
      weight categories using logistic regression. RESULTS: Low socioeconomic status
      (SES) (adjusted odds ratio [AOR] = 1.56 and p < .001, AOR = 1.35 and p = .0069,
      respectively) and higher soda intake (AOR = 1.07 and p = .0016, AOR = 1.08 and p
      = .0278, respectively) increased the odds of belonging to persistent
      overweight/obesity (30.6%) and deteriorated weight status (6.9%), compared to the
      persistent nonoverweight status group. CONCLUSION: While SES is an important
      determinant of weight category change, students' screen time and soda consumption
      may be important factors. Schools and families may be able to successfully focus
      on these modifiable risk factors, decreasing the burden of childhood obesity.

PMID- 25372232
TI  - Association of Concurrent Healthy Eating and Regular Physical Activity With
      Cardiovascular Disease Risk Factors in U.S. Youth.
AB  - PURPOSE: Examine whether concurrently consuming a healthy diet and regularly
      being physically active among U.S. youth is more favorably associated with
      cardiovascular disease (CVD) biomarkers than other physical activity and dietary
      patterns. DESIGN: Cross-sectional. SETTING: United States (National Health and
      Nutrition Examination Survey) 2003-2006. SUBJECTS: Two thousand six hundred
      twenty-nine youth (6-17 years). MEASURES: Healthy Eating Index (HEI),
      accelerometer-determined physical activity, biomarkers, and anthropometry. Four
      categories were created: consuming a healthy diet (top 40% of HEI) and active
      (sufficient to meet guidelines); unhealthy diet and active; healthy diet and
      inactive; and unhealthy diet and inactive. ANALYSIS: Multivariable regression.
      RESULTS: Children consuming a healthy diet and who were active had significantly
      lower waist circumference (beta = -5.5, p < .006), C-reactive protein (CRP) (beta
      = -.2, p < .006), and triglycerides (beta = -27.9, p < .006) than children
      consuming an unhealthy diet and who were inactive. Children engaging in both
      healthy behaviors had significantly lower CRP (beta = -.11, p < .001) and total
      cholesterol levels (beta = -7.8, p = .004) than those only engaging in sufficient
      activity; there were no significant differences in biomarker levels among
      children engaging in both healthy behaviors and those only consuming a healthy
      diet. No associations were significant for adolescents. CONCLUSION: Concurrent
      healthy eating and regular physical activity among children is favorably
      associated with CVD biomarkers when compared with unhealthy diet and inactivity.

PMID- 25372233
TI  - Receipt and timing of pregnancy-related preventive health messages vary by
      message type and maternal characteristics.
AB  - PURPOSE: To determine when women receive pregnancy-related preventive health
      messages and to examine differences in receipt timing by maternal
      characteristics. DESIGN: The cross-sectional secondary analyses used data from
      the Pregnancy Risk Assessment Monitoring System (PRAMS). SETTING: The study used
      PRAMS responses from Maryland, Michigan, New Jersey, Ohio. SUBJECTS: Study
      participants were women with a recent live birth. MEASURES: Health messages
      included mental health, safe medications, smoking, alcohol, and illegal drugs.
      The timing of message receipt was categorized as early (preconceptionally and
      prenatally) or late (prenatally only/never). ANALYSIS: Weighted chi (2) tests and
      multivariable logistic regression were used for analysis. RESULTS: Among n =
      3446, women with unintended pregnancies received all messages, except safe
      medications, significantly more early vs. late compared with women intending
      pregnancies (all p < .01). In multivariable analyses, there were no significant
      associations between timing of receipt and pregnancy intention, parity,
      preconception insurance status, or adequacy of prenatal care for any of the
      health messages. Hispanic women had increased odds of receiving the messages
      early compared with non-Hispanic white women, as did high school graduates vs.
      women with more education and women with lower household incomes vs. women with
      higher incomes. CONCLUSIONS: Women who may be perceived to be at higher risk of
      adverse pregnancy outcomes and/or engaging in high-risk behavior (minorities,
      lower education, lower income) appear to be getting messages early more often
      than do other women; messages are not reaching all women equally.

PMID- 25372234
TI  - Municipal Officials' Participation in Built Environment Policy Development in the
      United States.
AB  - PURPOSE: This study examined municipal officials' participation in built
      environment policy initiatives focused on land use design, transportation, and
      parks and recreation. DESIGN: Web-based cross-sectional survey. SETTING: Eighty
      three municipalities with 50,000 or more residents in eight states. SUBJECTS:
      Four hundred fifty-three elected and appointed municipal officials. MEASURES:
      Outcomes included self-reported participation in land use design, transportation,
      and parks and recreation policy to increase physical activity. Independent
      variables included respondent position; perceptions of importance, barriers, and
      beliefs regarding physical activity and community design and layout; and physical
      activity partnership participation. ANALYSIS: Multivariable logistic regression
      models. RESULTS: Compared to other positions, public health officials had lower
      participation in land use design (78.3% vs. 29.0%), transportation (78.1% vs.
      42.1%), and parks and recreation (67.1% vs. 26.3%) policy. Perceived limited
      staff was negatively associated with participation in each policy initiative.
      Perceptions of the extent to which physical activity was considered in community
      design and physical activity partnership participation were positively associated
      with participation in each. Perceived lack of collaboration was associated with
      less land use design and transportation policy participation, and awareness that
      community design affects physical activity was associated with more
      participation. Perceived lack of political will was associated with less parks
      and recreation policy participation. CONCLUSION: Public health officials are
      underrepresented in built environment policy initiatives. Improving
      collaborations may improve municipal officials' policy participation.

PMID- 25372235
TI  - Relationship between intervention dose and outcomes in living well with diabetes-
      a randomized trial of a telephone-delivered lifestyle-based weight loss
      intervention.
AB  - PURPOSE: To examine associations of intervention dose with weight, physical
      activity, glycemic control, and diet outcomes in a randomized trial of a
      telephone counseling intervention. DESIGN: Study design was a secondary analysis
      of intervention group. SETTING: Study setting was primary care practices in a
      disadvantaged community in Australia. SUBJECTS: Participants were adult patients
      with type 2 diabetes (n = 151). INTERVENTION: Up to 27 telephone counseling calls
      were made during 18 months. MEASURES: Intervention dose was assessed as the
      number of calls completed (in tertile categories). Primary outcomes were weight
      and HbA1c, and moderate to vigorous intensity physical activity via
      accelerometer. Secondary outcomes were dietary energy intake and diet quality via
      a validated questionnaire. ANALYSIS: Analyses employed were bivariate
      associations of call completion with sociodemographics, and confounder-adjusted
      linear mixed models for associations of call completion with outcomes (multiple
      imputation of missing data). RESULTS: Only previous diagnosis of
      depression/anxiety had a statistically significant (p = .008) association with
      call completion. Call completion was significantly associated with weight loss (p
      < .001) but not the other outcomes (p > .05). Relative to low call completion,
      mean weight loss (as a percentage of baseline weight) was greater in the high
      call completion group by -3.3% (95% confidence interval, -5.0% to -1.5%).
      CONCLUSION: Increased dose of intervention was associated with greater weight
      loss. More needs to be done to retain patients for the duration of weight loss
      and behavior change interventions, particularly those with diabetes and comorbid
      depression, who were the most difficult to engage.

PMID- 25372236
TI  - Using mass media campaigns to reduce youth tobacco use: a review.
AB  - OBJECTIVE: This review synthesizes the published literature on using mass media
      campaigns to reduce youth tobacco use, with particular focus on effects within
      population subgroups and the relative effectiveness of campaign characteristics.
      DATA SOURCE: A search of PubMed and PsycINFO conducted in March of 2014 yielded
      397 studies with 34 suitable for inclusion. STUDY INCLUSION AND EXCLUSION
      CRITERIA: Included were quantitative studies that evaluate an antitobacco media
      campaign intended to influence youth cognitions or behavior or explore the
      relative effectiveness of campaign characteristics among youth. DATA EXTRACTION:
      An automated search and assessment of suitability for inclusion was done. DATA
      SYNTHESIS: Study outcomes were compared and synthesized. RESULTS: Antitobacco
      media campaigns can be effective across racial/ethnic populations, although the
      size of the campaign effect may differ by race/ethnicity. Evidence is
      insufficient to determine whether campaign outcomes differ by socioeconomic
      status (SES) and population density. Youth are more likely to recall and think
      about advertising that includes personal testimonials; a surprising narrative;
      and intense images, sound, and editing. Evidence in support of using a health
      consequences message theme is mixed; an industry manipulation theme may be
      effective in combination with a health consequences message. Research is
      insufficient to determine whether advertising with a secondhand smoke or social
      norms theme influences youth tobacco use. CONCLUSION: Our recommendation is to
      develop antitobacco campaigns designed to reach all at-risk youth, which can be
      effective across racial/ethnic populations. Research priorities include assessing
      campaign influence among lower SES and rural youth, disentangling the effects of
      message characteristics, and assessing the degree to which this body of evidence
      may have changed as a result of changes in youth culture and communication
      technology.

PMID- 25372237
TI  - Screening and Counseling for Tobacco Use in Student Health Clinics: Reports of
      Health Care Providers.
AB  - PURPOSE: To assess tobacco screening and counseling in student health clinics,
      including facilitators, barriers, and associations with campus- and state-level
      variables. DESIGN: We conducted a mixed-methods study with an online survey and
      qualitative interviews. SETTING: Study setting was student health clinics on
      college campuses. SUBJECTS: Subjects included 71 clinic directors or designees
      from 10 Southeastern states (quantitative survey) and 8 directors or designees
      from 4 Southeastern states (qualitative interviews). MEASURES: Quantitative
      measures included demographics, screening and counseling practices, clinic-level
      supports for such practices, perceptions of tobacco on campus, institution size,
      public/private status, state tobacco farming revenue, and state tobacco control
      funding. Qualitative measures included barriers and facilitators of tobacco
      screening and counseling practices. ANALYSIS: Logistic and linear regression
      models assessed correlates of screening and counseling. Qualitative data were
      analyzed using multistage interpretive thematic analysis. RESULTS: A total of 55%
      of online survey respondents reported that their clinics screen for tobacco at
      every visit, whereas 80% reported their clinics offer counseling and
      pharmacotherapy. Barriers included lack of the following: time with patients,
      relevance to chief complaint, student self-identification as a tobacco user,
      access to pharmacotherapy, and interest in quitting among smokers. In
      multivariable models, more efforts to reduce tobacco use, student enrollment, and
      state-level cash receipts for tobacco were positively associated with clinic
      level supports. CONCLUSION: This study highlights missed opportunities for
      screening. Although reports of counseling were higher, providers identified many
      barriers.

PMID- 25372238
TI  - Factors influencing physical activity behaviors in colorectal cancer survivors.
AB  - PURPOSE: To elucidate factors that impact intention (INT) to be active as well as
      actual physical activity (PA) behavior in colorectal cancer survivors (CRC-S)
      using the theory of planned behavior (TpB). Planning for PA was explored as a
      mediator of the INT-behavior relationship. Chemotherapy-induced neuropathy and
      fatigue were also explored. DESIGN: A cross-sectional quantitative mailed survey
      was used. SETTING: The study was conducted among community-dwelling adults living
      in Pennsylvania when diagnosed with colorectal cancer (CRC). SUBJECTS: Subjects
      comprised 843 CRC-S diagnosed with CRC in Pennsylvania in 2009. MEASURES: The
      survey included questions about planning for PA, TpB constructs, medical and
      social variables, and PA as measured by a modified Godin Leisure Time
      Questionnaire. ANALYSIS: Descriptive statistics were used to characterize the
      sample. A mediation analysis was used to determine if planning mediated the
      relationship between INT and actual PA behavior. A stepwise regression was used
      to determine predictors of INT and PA. RESULTS: Ninety-six CRC-S responded, with
      25% meeting PA recommendations for health promotion, suggesting that CRC-S are
      insufficiently active. Perceived behavioral control (PBC) and social norm (SN)
      accounted for 43% of the variance in INT, whereas 30% of the variance in PA was
      explained by PBC and age. Neuropathy negatively impacted PA behavior (p = .008).
      Both action and coping planning partially mediated the INT-behavior relationship
      (beta = 20.08, p = .007; beta = 22.85, p = .001, respectively). CONCLUSION:
      Survivors at risk for inactivity are those with low PBC, low SN, and neuropathy,
      and those who are older.

PMID- 25372239
TI  - The Association of Meal Practices and Other Dietary Correlates With Dietary
      Intake Among High School Students in the United States, 2010.
AB  - PURPOSE: To examine behavioral and environmental factors that may be related to
      dietary behaviors among U.S. high school students. DESIGN: Data were obtained
      from the 2010 National Youth Physical Activity and Nutrition Study, a cross
      sectional study. SETTING: The study was school-based. SUBJECTS: Study subjects
      were a nationally representative sample of students in grades 9 to 12 (n =
      11,458). MEASURES: Variables of interest included meal practices, in-home snack
      availability, and intakes of healthful foods/beverages (fruits, vegetables,
      water, and milk) and less healthful foods/beverages (fried potatoes, pizza, and
      sugar-sweetened beverages). ANALYSIS: Sex-stratified logistic regression models
      were used to examine associations of meal practices and snack availability with
      dietary intake. Odds ratios (ORs) were adjusted for race/ethnicity and grade.
      RESULTS: Eating breakfast daily, frequent family dinners, and bringing lunch from
      home were associated with higher odds of consuming at least three healthful foods
      or beverages. High fast-food intake was associated with lower odds of healthful
      dietary intake and higher odds of sugar-sweetened beverage intake (female OR =
      3.73, male OR = 4.60). Students who mostly/always had fruits and vegetables
      available at home had increased odds of fruits (female OR = 3.04, male OR =
      2.24), vegetables (female OR = 2.12, male OR = 1.65), water (female OR = 1.82,
      male OR = 1.85), and milk intake (female OR = 1.45, male OR = 1.64). CONCLUSION:
      Encouraging daily breakfast consumption, frequent family dinners, and fruit and
      vegetable availability at home may lead to higher intakes of healthful foods
      among high school students.

PMID- 25372240
TI  - Knowledge of sugar content of sports drinks is not associated with sports drink
      consumption.
AB  - PURPOSE: To examine U.S. adult knowledge of the sugar content of sports drinks
      and whether this knowledge and other characteristics are associated with their
      sports drink consumption. DESIGN: Nonexperimental. SETTING: Nationally
      representative 2011 Summer ConsumerStyles survey data. SUBJECTS: 3929 U.S.
      adults. MEASURES: The outcome variable was sports drink consumption in the past 7
      days. The main exposure variable was knowledge about sports drinks containing
      sugar. The covariates were sociodemographic characteristics, physical activity,
      and weight status. ANALYSIS: Multivariable logistic regression analysis was used
      to estimate adjusted odds ratios (ORs) for adults consuming sports drinks >=1
      times/wk after controlling for other characteristics. RESULTS: Approximately 22%
      of adults reported consuming sports drinks >=1 times/wk. Most adults (71%) agreed
      that sports drinks contain sugar; however, this agreement was not significantly
      associated with adults' sports drink consumption. The odds of drinking sports
      drinks >=1 times/wk were significantly higher among younger adults aged 18 to 64
      years (OR range: 5.46-2.71), males (OR = 2.09), high-school graduates (OR =
      1.52), and highly active adults (OR = 2.09). CONCLUSION: There were disparities
      in sports drink consumption by sociodemographic characteristics and physical
      activity level; however, knowledge of sports drinks' sugar content was not
      associated with consumption. Understanding why some population groups are higher
      consumers may assist in the development of education, providing those groups with
      a better understanding of sports drinks' nutritional value and health
      consequences of excessive sugar consumption in any form.

PMID- 25372241
TI  - Comparison of plasma and tissue disposition of enrofloxacin in rainbow trout
      (Oncorhynchus mykiss) and common carp (Cyprinus carpio) after a single oral
      administration.
AB  - The aim of the study was to investigate the serum and tissue disposition of
      enrofloxacin and its active metabolite ciprofloxacin in rainbow trout
      (Oncorhynchus mykiss) and common carp (Cyprinus carpio) after a single oral
      administration at a dose of 10 mg kg(-1). Concentrations of enrofloxacin in the
      serum of rainbow trout showed high variability with two peaks at the third and
      24th hour after administration. The highest concentrations were found in the
      liver. The curves of liver levels showed similar changes to the respective serum
      samples. In the muscles, enrofloxacin concentrations were also higher compared
      with the respective serum samples. Ciprofloxacin concentrations were lower and
      showed smaller variations in all investigated tissues. The serum and tissue
      concentrations of enrofloxacin and ciprofloxacin in common carp showed two peaks,
      with the first Cmax at the third hour after drug administration as in rainbow
      trout. Concentrations of both investigated substances were higher in the liver
      than in the serum. The differences in common carp were less pronounced in
      comparison with rainbow trout. Relatively high levels of both substances were
      found in the muscles. Seven days after treatment enrofloxacin concentrations in
      the serum and tissues were within the therapeutic levels for most of the
      sensitive microorganisms in trout. Lower concentrations of its metabolite
      ciprofloxacin were found in the investigated tissues at the last sampling point.
      Lower levels of both substances were found in carp. 

PMID- 25372243
TI  - CMS Frailty Adjustment Model.
AB  - The authors document the development of the CMS frailty adjustment model, a
      Medicare payment approach that adjusts payments to a Medicare managed care
      organization (MCO) according to the functional impairment of its community
      residing enrollees. Beginning in 2004, this approach is being applied to certain
      organizations, such as Program of All-Inclusive Care for the Elderly (PACE), that
      specialize in providing care to the community-residing frail elderly. In the
      future, frailty adjustment could be extended to more Medicare managed care
      organizations.

PMID- 25372244
TI  - Evolution of Medicaid Coverage of Medicare Cost Sharing.
AB  - State Medicaid agencies are required to assist low-income Medicare beneficiaries
      to pay Medicare cost sharing, defined as premiums, deductibles, and coinsurance,
      as follows: all cost sharing for those below the Federal poverty level (FPL) and
      otherwise qualifying; Part B premiums for persons with incomes 100-120 percent of
      FPL; all or a portion Part B premiums for persons 120-175 percent of FPL, limited
      by funding availability; Part A premiums for persons with disabilities who have
      worked their way off Social Security and whose incomes are below 200 percent of
      FPL. States also have the option to extend additional protections or to cover
      additional Medicare beneficiaries beyond what is mandated by Federal law.
      Obviously, Federal changes in Medicare may have profound, if not always
      anticipated, implications for Medicaid. Understanding how current policy on
      dually eligible beneficiaries came into being may help shape what it will become.

PMID- 25372242
TI  - Does the Cultural Formulation Interview for the fifth revision of the diagnostic
      and statistical manual of mental disorders (DSM-5) affect medical communication?
      A qualitative exploratory study from the New York site.
AB  - OBJECTIVES: Cross-cultural mental health researchers often analyze patient
      explanatory models of illness to optimize service provision. The Cultural
      Formulation Interview (CFI) is a cross-cultural assessment tool released in May
      2013 with DSM-5 to revise shortcomings from the DSM-IV Outline for Cultural
      Formulation (OCF). The CFI field trial took place in 6 countries, 14 sites, and
      with 321 patients to explore its feasibility, acceptability, and clinical utility
      with patients and clinicians. We sought to analyze if and how CFI feasibility,
      acceptability, and clinical utility were related to patient-clinician
      communication. DESIGN: We report data from the New York site which enrolled 7
      clinicians and 32 patients in 32 patient-clinician dyads. We undertook a data
      analysis independent of the parent field trial by conducting content analyses of
      debriefing interviews with all participants (n = 64) based on codebooks derived
      from frameworks for medical communication and implementation outcomes. Three
      coders created codebooks, coded independently, established inter-rater coding
      reliability, and analyzed if the CFI affects medical communication with respect
      to feasibility, acceptability, and clinical utility. RESULTS: Despite racial,
      ethnical, cultural, and professional differences within our group of patients and
      clinicians, we found that promoting satisfaction through the interview, eliciting
      data, eliciting the patient's perspective, and perceiving data at multiple levels
      were common codes that explained how the CFI affected medical communication. We
      also found that all but two codes fell under the implementation outcome of
      clinical utility, two fell under acceptability, and none fell under feasibility.
      CONCLUSION: Our study offers new directions for research on how a cultural
      interview affects patient-clinician communication. Future research can analyze
      how the CFI and other cultural interviews impact medical communication in
      clinical settings with subsequent effects on outcomes such as medication
      adherence, appointment retention, and health condition.

PMID- 25372245
TI  - Transfer of silica-coated magnetic (Fe3O4) nanoparticles through food: a
      molecular and morphological study in zebrafish.
AB  - The increasing use of magnetic iron oxide nanoparticles (NPs) in biomedical
      applications has prompted extensive investigation of their interactions with
      biological systems also through animal models. A variety of toxic effects have
      been detected in NP-exposed fish and fish embryos, including oxidative stress and
      associated changes, such as lipid oxidation, apoptosis, and gene expression
      alterations. The main exposure route for fish is through food and the food web.
      This study was devised to investigate the effects of silica-coated NP
      administration through food in zebrafish (ZF, Danio rerio). Silica-coated
      magnetic NPs were administered to ZF through feed (zooplankton) from day 1 to 15
      posthatching (ph). Larvae were examined 6 and 15 days ph and adults 3 and 6
      months ph. A multidisciplinary approach, including morphometric examination;
      light, transmission electron, and confocal microscopy; inductively coupled plasma
      emission spectrometry; and real-time polymerase chain reaction, was applied to
      detect NP accumulation, structural and ultrastructural damage, and activation of
      detoxification processes in larvae and adults. Our findings document that the
      silica-coated NPs: (1) do not induce toxicity in ZF, (2) are excreted through
      feces, and (3) do not activate detoxification processes or promote tissue/cell
      injury.

PMID- 25372246
TI  - Health Care Indicators.
AB  - THIS REGULAR FEATURE OF THE JOURNAL INCLUDES A DISCUSSION OF EACH OF THE
      FOLLOWING FOUR TOPICS: community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25372247
TI  - Key Milestones in Medicare and Medicaid History, Selected Years: 1965-2003.

PMID- 25372248
TI  - Racial and Ethnic Differences in Hospitalization Rates Among Aged Medicare
      Beneficiaries, 1998.
AB  - Efforts to study racial variations in access to health care for minorities other
      than black persons have been hampered by a paucity of data. The Health Care
      Financing Administration (HCFA) has made efforts in the past few years to enhance
      the racial codes on the Medicare enrollment files to include Hispanic, Asian
      American, and Native American designations. This study examines hospitalization
      rates by these more detailed racial/ethnic groupings. The results show black,
      Hispanic, and Native American aged beneficiaries compared with white
      beneficiaries have higher hospitalization rates. Asian American beneficiaries
      have lower hospitalization rates. Rates of revascularization-coronary artery
      bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA)-are
      lower for black, Hispanic, and Native American beneficiaries compared with white
      beneficiaries, while rates for Asian Americans are similar to rates for white
      beneficiaries.

PMID- 25372249
TI  - Challenges facing our specialty.

PMID- 25372250
TI  - ICD-10 codes: more specificity with more characters.

PMID- 25372251
TI  - Private practice will survive but patient billing will not.

PMID- 25372252
TI  - Topical therapy for acne in women: is there a role for clindamycin phosphate
      benzoyl peroxide gel?
AB  - Acne vulgaris (AV) in adult women is commonly encountered in clinical dermatology
      practice. This patient subset often experiences psychosocial effects that differ
      in some ways from those experienced by adolescent females with AV, as they were
      not expecting to have to deal with this disorder beyond their adolescent years.
      Most of the emphasis on therapy for adult women with AV has focused on use of
      oral contraceptives (OCs) and/or oral spironolactone, with little to no
      evaluation or discussion of topical agents in this patient group. This article
      provides an overview of AV in adult women and presents the results of a
      subanalysis of data from female patients who were treated in phase 3 studies with
      clindamycin phosphate (CP) 1.2%-benzoyl peroxide (BP) 2.5% gel once daily for
      facial AV. The subanalysis compared outcomes in females younger than 25 years and
      in those 25 years and older. Overall, the data showed that therapeutic outcomes
      were comparable between the 2 groups.

PMID- 25372254
TI  - US dermatology residency program rankings.
AB  - Unlike many other adult specialties, US News & World Report does not rank
      dermatology residency programs annually. We conducted a study to rank individual
      US dermatology residency programs based on set criteria. For each residency
      program, data from 2008 related to a number of factors were collected, including
      annual amount of National Institutes of Health (NIH) and Dermatology Foundation
      (DF) funding received; number of publications from full-time faculty members;
      number of faculty lectures given at 5 annual society meetings; and number of full
      time faculty members who were on the editorial boards of 6 dermatology journals
      with the highest impact factors. Most of the data were obtained through extensive
      Internet searches, and missing data were obtained by contacting individual
      residency programs. The programs were ranked based on the prior factors according
      to a weighted ranking algorithm. A list of overall rankings also was created.

PMID- 25372253
TI  - Allergic contact dermatitis to 2-octyl cyanoacrylate.
AB  - Cyanoacrylates are widely used as topical skin adhesives in emergency
      departments, clinics, and operating rooms. We report 4 patients who developed
      allergic contact dermatitis (ACD) following postsurgical closure with 2-octyl
      cyanoacrylate. These patients were challenged with a novel method of use testing
      to confirm sensitivity to 2-octyl cyanoacrylate. The popularity of skin adhesives
      makes this emerging allergen worthy of examination. It is possible that
      cyanoacrylate allergy currently is underrecognized.

PMID- 25372255
TI  - Granulomatous changes associated with pigmented purpuric dermatosis.
AB  - Granulomatous pigmented purpuric dermatosis (GPPD) is a rare entity with few
      cases reported in the literature. We report 3 cases of pigmented purpuric
      dermatosis (PPD) with granulomatous features in a 9-year-old boy, a 49-year-old
      woman, and a 75-year-old woman. We also review the literature on PPDs with
      granulomatous features, including histopathologic features and disease
      associations. Most of the cases we reviewed described granulomas superimposed on
      classic changes of PPD. We also identify a new variant of GPPD in 2 of our
      patients who presented with granulomatous infiltrates in the mid to deep dermis.
      Granulomatous PPD does not appear to have a consistent association with
      underlying disease; notably, hyperlipidemia was seen in 7 cases we reviewed. 

PMID- 25372256
TI  - Unilateral generalized keratosis pilaris following pregnancy.
AB  - Keratosis pilaris (KP) is a common inherited disorder characterized by small
      folliculocentric keratotic papules that may have surrounding erythema, which
      gives the skin a stippled appearance resembling gooseflesh. The extensor surfaces
      of the upper arms, thighs, and buttocks commonly are affected, but a generalized
      presentation may occur. We report the case of a 29-year-old woman with unilateral
      generalized KP in the second month of her second pregnancy. Both a genetic
      mutation and pregnancy-induced hormonal changes played possible roles in the
      development and progress of unilateral generalized KP in this patient. 

PMID- 25372257
TI  - Pemphigus vulgaris in pregnancy.
AB  - We report the case of a 34-year-old woman who was diagnosed with pemphigus
      vulgaris (PV) during pregnancy. The patient presented with widespread blistering
      dermatitis and associated burning and pruritus. At 6 weeks' gestation the patient
      was admitted to the hospital to expedite her diagnosis and initiate treatment. A
      skin biopsy revealed suprabasal acantholysis, and direct immunofluorescence
      demonstrated diffuse intercellular IgG in the epidermis and basal intercellular
      C3, which confirmed the diagnosis of PV. Treatment with corticosteroids was
      instituted after discussions with the patient about possible adverse effects to
      the fetus. Pemphigus vulgaris is rare in pregnancy and active PV presents
      potential threats of fetal spread and transient lesion production, which is
      associated with increased mortality and morbidity in the fetus. Our patient had
      active PV and required treatment throughout her pregnancy. The pregnancy
      progressed to premature delivery of the neonate without skin lesions or apparent
      complications. 

PMID- 25372259
TI  - Lipidized dermatofibroma.

PMID- 25372258
TI  - What is your diagnosis? Rhino-orbital-cerebral mucormycosis.

PMID- 25372260
TI  - Asymptomatic annular plaques on the neck.

PMID- 25372261
TI  - Flurbiprofen-induced unilateral eyelid angioedema.

PMID- 25372262
TI  - Shave removal plus electrodesiccation for the treatment of cutaneous
      neurofibromas.

PMID- 25372263
TI  - An unusual presentation of congenital dermal melanocytosis fitting the rare
      diagnosis of dermal melanocyte hamartoma.

PMID- 25372264
TI  - HATS syndrome: hemimaxillary enlargement, asymmetry of the face, tooth
      abnormalities, and skin findings.
AB  - Hemimaxillary enlargement, asymmetry of the face, tooth abnormalities, and skin
      findings (HATS syndrome) is a rare developmental disorder involving the first and
      second branchial arches. Physical manifestations may present at birth or during
      early childhood. Characteristic findings include unilateral abnormalities of the
      face involving the bones, teeth, gums, and skin. Among the characteristic
      cutaneous manifestations of HATS syndrome, Becker nevus is the most common. A
      variety of modalities have been utilized in the treatment of HATS syndrome, but
      no standardized therapy has been established. We report a case of this rare
      condition in a 14-year-old adolescent boy.

PMID- 25372265
TI  - Learning dermatopathology in the digital age.
AB  - In recent years, advances in technology have allowed the study of pathology to
      transition into the digital realm. Histologic sections can now be viewed on
      mobile devices and computer screens easily and in many cases for free to increase
      exposure to representative learning cases. Many of these images have labels and
      markings to facilitate identification of key histologic findings. This article
      highlights some of the programs and Web sites that host these digital slides and
      rank them in the order of their utility to students of dermatopathology. 

PMID- 25372266
TI  - Erythematous seropurulent ulcerations.

PMID- 25372267
TI  - Atrophic plaques on the back.

PMID- 25372268
TI  - Spontaneously regressing primary nodular melanoma of the glans penis.

PMID- 25372272
TI  - Overview.

PMID- 25372271
TI  - Lower leptin/adiponectin ratio and risk of rapid lung function decline in chronic
      obstructive pulmonary disease.
AB  - RATIONALE: The rate of annual change in FEV1 is highly variable among patients
      with chronic obstructive pulmonary disease (COPD). Reliable blood biomarkers are
      needed to predict prognosis. OBJECTIVES: To explore plasma biomarkers associated
      with an annual change in FEV1 in patients with COPD. METHODS: Plasma samples of
      261 subjects, all Japanese, with COPD from the 5-year Hokkaido COPD cohort study
      were analyzed as a hypothesis-generating cohort, and the results were validated
      using data of 226 subjects with and 268 subjects without airflow limitation,
      mainly white, from the 4-year COPD Quantification by Computed Tomography,
      Biomarkers, and Quality of Life (CBQ) study conducted in Denmark. The plasma
      samples were measured using Human CardiovascularMAP (Myriad RBM, Austin, TX),
      which could analyze 50 biomarkers potentially linked with inflammatory,
      metabolic, and tissue remodeling pathways, and single ELISAs were used to confirm
      the results. MEASUREMENTS AND MAIN RESULTS: Higher plasma adiponectin levels and
      a lower leptin/adiponectin ratio at enrollment were significantly associated with
      an annual decline in FEV1 even after controlling for age, sex, height, and body
      mass index in the Hokkaido COPD cohort study (P = 0.003, P = 0.004,
      respectively). A lower plasma leptin/adiponectin ratio was also significantly
      associated with an annual decline in FEV1 in subjects with airflow limitation in
      the CBQ study (P = 0.014), the patients of which had largely different clinical
      characteristics compared with the Hokkaido COPD cohort study. There were no
      significant associations between lung function decline and adipokine levels in
      subjects without airflow limitation. CONCLUSIONS: A lower leptin/adiponectin
      ratio was associated with lung function decline in patients with COPD in two
      independent Japanese and Western cohort studies of populations of different
      ethnicity. Measure of systemic adipokines may provide utility in predicting
      patients with COPD at higher risk of lung function decline.

PMID- 25372273
TI  - Standing surface acoustic wave (SSAW)-based cell washing.
AB  - Cell/bead washing is an indispensable sample preparation procedure used in
      various cell studies and analytical processes. In this article, we report a
      standing surface acoustic wave (SSAW)-based microfluidic device for cell and bead
      washing in a continuous flow. In our approach, the acoustic radiation force
      generated in a SSAW field is utilized to actively extract cells or beads from
      their original medium. A unique configuration of tilted-angle standing surface
      acoustic wave (taSSAW) is employed in our device, enabling us to wash beads with
      >98% recovery rate and >97% washing efficiency. We also demonstrate the
      functionality of our device by preparing high-purity (>97%) white blood cells
      from lysed blood samples through cell washing. Our SSAW-based cell/bead washing
      device has the advantages of label-free manipulation, simplicity, high
      biocompatibility, high recovery rate, and high washing efficiency. It can be
      useful for many lab-on-a-chip applications. 

PMID- 25372275
TI  - Reduction in Central Line-Associated Bloodstream Infection Rates After
      Implementations of Infection Control Measures at a Level 3 Neonatal Intensive
      Care Unit.
AB  - Advances in neonatology led to survival of micro-preemies, who need central
      lines. Central line-associated bloodstream infection (CLABSI) causes prolonged
      hospitalization, morbidities, and mortality. Health care team education decreases
      CLABSIs. The objective was to decrease CLABSIs using evidence-based measures. The
      retrospective review compared CLABSI incidence during and after changes in
      catheter care. In April 2011, intravenous (IV) tubing changed from Interlink to
      Clearlink; IV tubing changing interval increased from 24 to 72 hours. CLABSIs
      increased. The following measures were implemented: July 2011, reeducation of
      neonatal intensive care staff on Clearlink; August 2011, IV tubing changing
      interval returned to 24 hours; September 2011, changed from Clearlink back to
      Interlink; November 2011, review of entire IV process and in-service on hand
      hygiene; December 2011, competencies on IV access for all nurses. CLABSIs were
      compared during and after interventions. Means were compared using the t test and
      ratios using the chi(2) test; P <.05. CLABSIs decreased from 4.4/1000 to 0/1000
      catheter-days; P < .05. Evidence-based interventions reduced CLABSIs.

PMID- 25372276
TI  - Imidazopyridine- and purine-thioacetamide derivatives: potent inhibitors of
      nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1).
AB  - Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) belongs to the family of
      ecto-nucleotidases, which control extracellular nucleotide, nucleoside, and
      (di)phosphate levels. To study the (patho)physiological roles of NPP1 potent and
      selective inhibitors with drug-like properties are required. Therefore, a
      compound library was screened for NPP1 inhibitors using a colorimetric assay with
      p-nitrophenyl 5'-thymidine monophosphate (p-Nph-5'-TMP) as an artificial
      substrate. This led to the discovery of 2-(3H-imidazo[4,5-b]pyridin-2-ylthio)-N
      (3,4-dimethoxyphenyl)acetamide (5a) as a hit compound with a Ki value of 217 nM.
      Subsequent structure-activity relationship studies led to the development of
      purine and imidazo[4,5-b]pyridine analogues with high inhibitory potency (Ki
      values of 5.00 nM and 29.6 nM, respectively) when assayed with p-Nph-5'-TMP as a
      substrate. Surprisingly, the compounds were significantly less potent when tested
      versus ATP as a substrate, with Ki values in the low micromolar range. A
      prototypic inhibitor was investigated for its mechanism of inhibition and found
      to be competitive versus both substrates. 

PMID- 25372274
TI  - Clinically important features of porphyrin and heme metabolism and the
      porphyrias.
AB  - Heme, like chlorophyll, is a primordial molecule and is one of the fundamental
      pigments of life. Disorders of normal heme synthesis may cause human diseases,
      including certain anemias (X-linked sideroblastic anemias) and porphyrias.
      Porphyrias are classified as hepatic and erythropoietic porphyrias based on the
      organ system in which heme precursors (5-aminolevulinic acid (ALA),
      porphobilinogen and porphyrins) are chiefly overproduced. The hepatic porphyrias
      are further subdivided into acute porphyrias and chronic hepatic porphyrias. The
      acute porphyrias include acute intermittent, hereditary copro-, variegate and ALA
      dehydratase deficiency porphyria. Chronic hepatic porphyrias include porphyria
      cutanea tarda and hepatoerythropoietic porphyria. The erythropoietic porphyrias
      include congenital erythropoietic porphyria (Gunther's disease) and
      erythropoietic protoporphyria. In this review, we summarize the key features of
      normal heme synthesis and its differing regulation in liver versus bone marrow.
      In both organs, principal regulation is exerted at the level of the first and
      rate-controlling enzyme, but by different molecules (heme in the liver and iron
      in the bone marrow). We also describe salient clinical, laboratory and genetic
      features of the eight types of porphyria. 

PMID- 25372277
TI  - Dynamics of cultural transmission in Native Americans of the high Great Plains.
AB  - Culture is a phenomenon shared by all humans. Attempts to understand how dynamic
      factors affect the origin and distribution of cultural elements are, therefore,
      of interest to all humanity. As case studies go, understanding the distribution
      of cultural elements in Native American communities during the historical period
      of the Great Plains would seem a most challenging one. Famously, there is a
      mixture of powerful internal and external factors, creating-for a relatively
      brief period in time-a seemingly distinctive set of shared elements from a
      linguistically diverse set of peoples. This is known across the world as the
      "Great Plains culture." Here, quantitative analyses show how different processes
      operated on two sets of cultural traits among nine High Plains groups. Moccasin
      decorations exhibit a pattern consistent with geographically-mediated between
      group interaction. However, group variations in the religious ceremony of the Sun
      Dance also reveal evidence of purifying cultural selection associated with
      historical biases, dividing down ancient linguistic lines. The latter shows that
      while the conglomeration of "Plains culture" may have been a product of merging
      new ideas with old, combined with cultural interchange between groups, the
      details of what was accepted, rejected or elaborated in each case reflected
      preexisting ideological biases. Although culture may sometimes be a "melting
      pot," the analyses show that even in highly fluid situations, cultural mosaics
      may be indirectly shaped by historical factors that are not always obvious. 

PMID- 25372278
TI  - Carbon nanodots: toward a comprehensive understanding of their photoluminescence.
AB  - We report the characterization of carbon nanodots (CNDs) synthesized under mild
      and controlled conditions, that is, in a microwave reactor. The CNDs thus
      synthesized exhibit homogeneous and narrowly dispersed optical properties. They
      are thus well suited as a testbed for studies of the photophysics of carbon-based
      nanoscopic emitters. In addition to steady-state investigations, time-correlated
      single-photon counting, fluorescence up-conversion, and transient pump probe
      absorption spectroscopy were used to elucidate the excited-state dynamics.
      Moreover, quenching the CND-based emission with electron donors or acceptors
      helped shed light on the nature of individual states. Density functional theory
      and semiempirical configuration-interaction calculations on model systems helped
      understand the fundamental structure-property relationships for this novel type
      of material. 

PMID- 25372279
TI  - The effect of the cation alkyl chain length on density and diffusion in
      dialkylpyrrolidinium bis(mandelato)borate ionic liquids.
AB  - The physicochemical properties of ionic liquids are strongly affected by the
      selective combination of the cations and anions comprising the ionic liquid. In
      particular, the length of the alkyl chains of ions has a clear influence on the
      ionic liquid's performance. In this paper, we study the self-diffusion of ions in
      a series of halogen-free boron-based ionic liquids (hf-BILs) containing
      bis(mandelato)borate anions and dialkylpyrrolidinium cations with long alkyl
      chains CnH2n+1 with n from 4 to 14 within a temperature range of 293-373 K. It
      was found that the hf-BILs with n = 4-7 have very similar diffusion coefficients,
      while hf-BILs with n = 10-14 exhibit two liquid sub-phases in almost the entire
      temperature range studied (293-353 K). Both liquid sub-phases differ in their
      diffusion coefficients, while values of the slower diffusion coefficients are
      close to those of hf-BILs with shorter alkyl chains. To explain the particular
      dependence of diffusion on the alkyl chain length, we examined the densities of
      the hf-BILs studied here. It was shown that the dependence of the density on the
      number of CH2 groups in long alkyl chains of cations can be accurately described
      using a "mosaic type" model, where regions of long alkyl chains of cations (named
      'aliphatic' regions) and the residual chemical moieties in both cations and
      anions (named 'ionic' regions) give additive contributions. Changes in density
      due to an increase in temperature and the number of CH2 groups in the long alkyl
      chains of cations are determined predominantly by changes in the free volume of
      the 'ionic' regions, while 'aliphatic' regions are already highly compressed by
      van der Waals forces, which results in only infinitesimal changes in their free
      volumes with temperature. 

PMID- 25372280
TI  - A long-term experimental study demonstrates the costs of begging that were not
      found over the short term.
AB  - Parent-offspring conflict theory predicts that begging behaviour could escalate
      continuously over evolutionary time if it is not prevented by costliness of
      begging displays. Three main potential physiological costs have been proposed:
      growth, immunological and metabolic costs. However, empirical evidence on this
      subject remains elusive because published results are often contradictory. In
      this study, we test for the existence of these three potential physiological
      costs of begging in house sparrow (Passer domesticus) nestlings by stimulating a
      group of nestlings to beg for longer and another group for shorter periods than
      in natural conditions. All nestlings were fed with the same quantity of food. Our
      study involves a long-term experimental treatment for begging studies (five
      consecutive days). Long-term studies frequently provide clearer results than
      short-term studies and, sometimes, relevant information not reported by the
      latter ones. Our long-term experiment shows (i) a clear effect on the immune
      response even since the first measurement (6 hours), but it was higher during the
      second (long-term) than during the first (short-term) test; (ii) evidence of a
      growth cost of begging in house sparrow nestlings not previously found by other
      studies; (iii) body condition was affected by our experimental manipulation only
      after 48 hour; (iv) a metabolic cost of begging never previously shown in any
      species, and (v) for the first time, it has shown a simultaneous effect of the
      three potential physiological costs of begging: immunocompetence, growth, and
      metabolism. This implies first, that a multilevel trade-off can occur between
      begging and all physiological costs and, second, that a lack of support in a
      short-term experiment for the existence of a tested cost of begging does not mean
      absence of that cost, because it can be found in a long-term experiment. 

PMID- 25372281
TI  - Foreign body response to subcutaneous implants in diabetic rats.
AB  - Implantation of synthetic matrices and biomedical devices in diabetic individuals
      has become a common procedure to repair and/or replace biological tissues.
      However, an adverse foreign body reaction that invariably occurs adjacent to
      implant devices impairing their function is poorly characterized in the diabetic
      environment. We investigated the influence of this condition on the abnormal
      tissue healing response in implants placed subcutaneously in normoglycemic and
      streptozotocin-induced diabetes in rats. In polyether-polyurethane sponge discs
      removed 10 days after implantation, the components of the fibrovascular tissue
      (angiogenesis, inflammation, fibrogenesis, and apoptosis) were assessed. Intra
      implant levels of hemoglobin and vascular endothelial growth factor were not
      different after diabetes when compared with normoglycemic counterparts. However,
      there were a lower number of vessels in the fibrovascular tissue from diabetic
      rats when compared with vessel numbers in implants from non-diabetic animals.
      Overall, the inflammatory parameters (neutrophil accumulation--myeloperoxidase
      activity, tumor necrosis factor alpha, and monocyte chemotactic protein-1 levels
      and mast cell counting) increased in subcutaneous implants after diabetes
      induction. However, macrophage activation (N-acetyl-beta-D-glucosaminidase
      activity) was lower in implants from diabetic rats when compared with those from
      normoglycemic animals. All fibrogenic markers (transforming growth factor beta 1
      levels, collagen deposition, fibrous capsule thickness, and foreign body giant
      cells) decreased after diabetes, whereas apoptosis (TUNEL) increased. Our results
      showing that hyperglycemia down regulates the main features of the foreign body
      reaction induced by subcutaneous implants in rats may be relevant in
      understanding biomaterial integration and performance in diabetes.

PMID- 25372282
TI  - Metabolomic profiling in cattle experimentally infected with Mycobacterium avium
      subsp. paratuberculosis.
AB  - The sensitivity of current diagnostics for Johne's disease, a slow, progressing
      enteritis in ruminants caused by Mycobacterium avium subsp. paratuberculosis
      (MAP), is too low to reliably detect all infected animals in the subclinical
      stage. The objective was to identify individual metabolites or metabolite
      profiles that could be used as biomarkers of early MAP infection in ruminants. In
      a monthly follow-up for 17 months, calves infected at 2 weeks of age were
      compared with aged-matched controls. Sera from all animals were analyzed by 1H
      nuclear magnetic resonance spectrometry. Spectra were acquired, processed, and
      quantified for analysis. The concentration of many metabolites changed over time
      in all calves, but some metabolites only changed over time in either infected or
      non-infected groups and the change in others was impacted by the infection.
      Hierarchical multivariate statistical analysis achieved best separation between
      groups between 300 and 400 days after infection. Therefore, a cross-sectional
      comparison between 1-year-old calves experimentally infected at various ages with
      either a high- or a low-dose and age-matched non-infected controls was performed.
      Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS DA)
      yielded distinct separation of non-infected from infected cattle, regardless of
      dose and time (3, 6, 9 or 12 months) after infection. Receiver Operating Curves
      demonstrated that constructed models were high quality. Increased isobutyrate in
      the infected cattle was the most important agreement between the longitudinal and
      cross-sectional analysis. In general, high- and low-dose cattle responded
      similarly to infection. Differences in acetone, citrate, glycerol and iso
      butyrate concentrations indicated energy shortages and increased fat metabolism
      in infected cattle, whereas changes in urea and several amino acids (AA),
      including the branched chain AA, indicated increased protein turnover. In
      conclusion, metabolomics was a sensitive method for detecting MAP infection much
      sooner than with current diagnostic methods, with individual metabolites
      significantly distinguishing infected from non-infected cattle. 

PMID- 25372284
TI  - Invasibility of Mediterranean-climate rivers by non-native fish: the importance
      of environmental drivers and human pressures.
AB  - Invasive species are regarded as a biological pressure to natural aquatic
      communities. Understanding the factors promoting successful invasions is of great
      conceptual and practical importance. From a practical point of view, it should
      help to prevent future invasions and to mitigate the effects of recent invaders
      through early detection and prioritization of management measures. This study
      aims to identify the environmental determinants of fish invasions in
      Mediterranean-climate rivers and evaluate the relative importance of natural and
      human drivers. Fish communities were sampled in 182 undisturbed and 198 disturbed
      sites by human activities, belonging to 12 river types defined for continental
      Portugal within the implementation of the European Union's Water Framework
      Directive. Pumpkinseed sunfish, Lepomis gibbosus (L.), and mosquitofish, Gambusia
      holbrooki (Girard), were the most abundant non-native species (NNS) in the
      southern river types whereas the Iberian gudgeon, Gobio lozanoi Doadrio and
      Madeira, was the dominant NNS in the north/centre. Small northern mountain
      streams showed null or low frequency of occurrence and abundance of NNS, while
      southern lowland river types with medium and large drainage areas presented the
      highest values. The occurrence of NNS was significantly lower in undisturbed
      sites and the highest density of NNS was associated with high human pressure.
      Results from variance partitioning showed that natural environmental factors
      determine the distribution of the most abundant NNS while the increase in their
      abundance and success is explained mainly by human-induced disturbance factors.
      This study stresses the high vulnerability of the warm water lowland river types
      to non-native fish invasions, which is amplified by human-induced degradation. 

PMID- 25372283
TI  - A blueberry-enriched diet improves renal function and reduces oxidative stress in
      metabolic syndrome animals: potential mechanism of TLR4-MAPK signaling pathway.
AB  - BACKGROUND: Metabolic syndrome (MetS) is characterized by a cluster of health
      factors that indicate a higher risk for cardio-renal diseases. Recent evidence
      indicates that antioxidants from berries are alternative to attenuate oxidative
      stress and inflammation. We tested the hypothesis that inflammation-induced renal
      damage is triggered by the activation of TLR4, and subsequent modulation of redox
      sensitive molecules and mitogen-activated protein kinase (MAPK) pathway. METHODS:
      Five-week old lean and obese Zucker rats (LZR and OZR) were fed a blueberry
      enriched diet or an isocaloric control diet for 15 weeks. A glucose tolerance
      test and acute renal clearance experiments were performed. Gene and protein
      expression levels for TLR4, cytokines and phosphorylation of ERK and p38MAPK were
      measured. Kidney redox status and urinary albumin levels were quantified. Renal
      pathology was evaluated histologically. RESULTS: Control OZR exhibited lower
      glucose tolerance; exacerbated renal function parameters; increased oxidative
      stress. Gene and protein expression levels of TLR4 were higher and this was
      accompanied by increased renal pathology with extensive albuminuria and
      deterioration in antioxidant levels in OZR. In addition, OZR had increased
      phosphorylation of ERK and p38MAPK. Blueberry-fed OZR exhibited significant
      improvements in all these parameters compared to OZR. CONCLUSION: TLR4-MAPK
      signaling pathway is a key to the renal structural injury and dysfunction in MetS
      and blueberry (BB) protect against this damage by inhibiting TLR4. SIGNIFICANCE:
      This is the first study to put forth a potential mechanism of TLR4-induced kidney
      damage in a model of MetS and to elucidate a downstream mechanism by which
      blueberry exert their reno-protective effects.

PMID- 25372285
TI  - A direct brain-to-brain interface in humans.
AB  - We describe the first direct brain-to-brain interface in humans and present
      results from experiments involving six different subjects. Our non-invasive
      interface, demonstrated originally in August 2013, combines
      electroencephalography (EEG) for recording brain signals with transcranial
      magnetic stimulation (TMS) for delivering information to the brain. We illustrate
      our method using a visuomotor task in which two humans must cooperate through
      direct brain-to-brain communication to achieve a desired goal in a computer game.
      The brain-to-brain interface detects motor imagery in EEG signals recorded from
      one subject (the "sender") and transmits this information over the internet to
      the motor cortex region of a second subject (the "receiver"). This allows the
      sender to cause a desired motor response in the receiver (a press on a touchpad)
      via TMS. We quantify the performance of the brain-to-brain interface in terms of
      the amount of information transmitted as well as the accuracies attained in (1)
      decoding the sender's signals, (2) generating a motor response from the receiver
      upon stimulation, and (3) achieving the overall goal in the cooperative
      visuomotor task. Our results provide evidence for a rudimentary form of direct
      information transmission from one human brain to another using non-invasive
      means. 

PMID- 25372286
TI  - Social determinants and the classification of disease: descriptive epidemiology
      of selected socially mediated disease constellations.
AB  - BACKGROUND: Most major diseases have important social determinants. In this
      context, classification of disease based on etiologic or anatomic criteria may be
      neither mutually exclusive nor optimal. METHODS AND FINDINGS: Units of analysis
      comprised large metropolitan central and fringe metropolitan counties with
      reliable mortality rates--(n = 416). Participants included infants and adults
      ages 25 to 64 years with selected causes of death (1999 to 2006). Exposures
      included that residential segregation and race-specific social deprivation
      variables. Main outcome measures were obtained via principal components analyses
      with an orthogonal rotation to identify a common factor. To discern whether the
      common factor was socially mediated, negative binomial multiple regression models
      were developed for which the dependent variable was the common factor. Results
      showed that infant deaths, mortality from assault, and malignant neoplasm of the
      trachea, bronchus and lung formed a common factor for race-gender groups
      (black/white and men/women). Regression analyses showed statistically
      significant, positive associations between low socio-economic status for all race
      gender groups and this common factor. CONCLUSIONS: Between 1999 and 2006, deaths
      classified as "assault" and "lung cancer", as well as "infant mortality" formed a
      socially mediated factor detectable in population but not individual data.
      Despite limitations related to death certificate data, the results contribute
      important information to the formulation of several hypotheses: (a) disease
      classifications based on anatomic or etiologic criteria fail to account for
      social determinants; (b) social forces produce demographically and possibly
      geographically distinct population-based disease constellations; and (c) the
      individual components of population-based disease constellations (e.g., lung
      cancer) are phenotypically comparable from one population to another but
      genotypically different, in part, because of socially mediated epigenetic
      variations. Additional research may produce new taxonomies that unify social
      determinants with anatomic and/or etiologic determinants. This may lead to
      improved medical management of individuals and populations.

PMID- 25372287
TI  - High-throughput sequencing and copy number variation detection using formalin
      fixed embedded tissue in metastatic gastric cancer.
AB  - In the era of targeted therapy, mutation profiling of cancer is a crucial aspect
      of making therapeutic decisions. To characterize cancer at a molecular level, the
      use of formalin-fixed paraffin-embedded tissue is important. We tested the Ion
      AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay in 89
      formalin-fixed paraffin-embedded gastric cancer samples to determine whether they
      are applicable in archival clinical samples for personalized targeted therapies.
      We validated the results with Sanger sequencing, real-time quantitative PCR,
      fluorescence in situ hybridization and immunohistochemistry. Frequently detected
      somatic mutations included TP53 (28.17%), APC (10.1%), PIK3CA (5.6%), KRAS
      (4.5%), SMO (3.4%), STK11 (3.4%), CDKN2A (3.4%) and SMAD4 (3.4%). Amplifications
      of HER2, CCNE1, MYC, KRAS and EGFR genes were observed in 8 (8.9%), 4 (4.5%), 2
      (2.2%), 1 (1.1%) and 1 (1.1%) cases, respectively. In the cases with
      amplification, fluorescence in situ hybridization for HER2 verified gene
      amplification and immunohistochemistry for HER2, EGFR and CCNE1 verified the
      overexpression of proteins in tumor cells. In conclusion, we successfully
      performed semiconductor-based sequencing and nCounter copy number variation
      analyses in formalin-fixed paraffin-embedded gastric cancer samples. High
      throughput screening in archival clinical samples enables faster, more accurate
      and cost-effective detection of hotspot mutations or amplification in genes. 

PMID- 25372290
TI  - Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship
      between valproic acid exposure and elevation of gamma-glutamyltransferase in
      patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.
AB  - BACKGROUND: There has been accumulating evidence that there are associations
      among gamma-glutamyltransferase (gamma-GT) elevation and all-cause mortality,
      cardiovascular diseases and metabolic diseases, including nonalcoholic fatty
      liver disease. The primary objective of this study was to evaluate the impact of
      the most common and potentially functional polymorphisms of antioxidant enzyme
      genes, i.e. superoxide dismutase 2 (SOD2), glutathione S-transferase M1 and
      glutathione S-transferase T1, on the gamma-GT elevation during valproic acid
      (VPA) therapy. METHODS AND FINDINGS: This retrospective study included 237 and
      169 VPA-treated Japanese patients with epilepsy for population pharmacokinetic
      and pharmacokinetic-pharmacodynamic analyses, respectively. A nonlinear mixed
      effect model represented the pharmacokinetics of VPA and the relationships
      between VPA exposure and gamma-GT elevation. A one-compartment model of the
      pharmacokinetic parameters of VPA adequately described the data; while the model
      for the probability of the gamma-GT elevation was fitted using a logistic
      regression model, in which the logit function of the probability was a linear
      function of VPA exposure. The SOD2 Val16Ala polymorphism and complication with
      intellectual disability were found to be significant covariates influencing the
      intercept of the logit function for the probability of an elevated gamma-GT
      level. The predicted mean percentages of the subjects with gamma-GT elevation
      were about 2- to 3-fold, 3- to 4-fold and 4- to 8-fold greater in patients with
      the SOD2 Val/Val genotype but without any intellectual disability, those with the
      SOD2 Val/Ala or Ala/Ala genotype and intellectual disability and those with the
      SOD2 Val/Val genotype and intellectual disability, respectively, compared to
      those with the SOD2 Val/Ala or Ala/Ala genotype without intellectual disability.
      CONCLUSION: Our results showed that the SOD2 Val16Ala polymorphism has an impact
      on the relationship between VPA exposure and gamma-GT elevation in patients with
      epilepsy. These results suggest that determining the SOD2 genotype could be
      helpful for preventing the VPA-induced gamma-GT elevation.

PMID- 25372289
TI  - Live imaging and gene expression analysis in zebrafish identifies a link between
      neutrophils and epithelial to mesenchymal transition.
AB  - Chronic inflammation is associated with epithelial to mesenchymal transition
      (EMT) and cancer progression however the relationship between inflammation and
      EMT remains unclear. Here, we have exploited zebrafish to visualize and quantify
      the earliest events during epithelial cell transformation induced by oncogenic
      HRas(V12). Live imaging revealed that expression of HRas(V12) in the epidermis
      results in EMT and chronic neutrophil and macrophage infiltration. We have
      developed an in vivo system to probe and quantify gene expression changes
      specifically in transformed cells from chimeric zebrafish expressing oncogenic
      HRas(V12) using translating ribosomal affinity purification (TRAP). We found that
      the expression of genes associated with EMT, including slug, vimentin and mmp9,
      are enriched in HRas(V12) transformed epithelial cells and that this enrichment
      requires the presence of neutrophils. An early signal induced by HRas(V12) in
      epithelial cells is the expression of il-8 (cxcl8) and we found that the
      chemokine receptor, Cxcr2, mediates neutrophil but not macrophage recruitment to
      the transformed cells. Surprisingly, we also found a cell autonomous role for
      Cxcr2 signaling in transformed cells for both neutrophil recruitment and EMT
      related gene expression associated with Ras transformation. Taken together, these
      findings implicate both autocrine and paracrine signaling through Cxcr2 in the
      regulation of inflammation and gene expression in transformed epithelial cells.

PMID- 25372291
TI  - Bi-epitope SPR surfaces: a solution to develop robust immunoassays.
AB  - Surface plasmon resonance (SPR)-based immunoassays have numerous applications and
      require high affinity reagents for sensitive and reliable measurements. We
      describe a quick approach to turn low affinity antibodies into appropriate
      capture reagents. We used antibodies recognizing human ephrin type A receptor 2
      (EphA2) and a ProteOn XPR36 as a model system. We generated so-called 'bi
      epitope' sensor surfaces by immobilizing various pairs of anti-EphA2 antibodies
      using standard amine coupling. The apparent binding affinities to EphA2 and EphA2
      detection sensitivities of the bi-epitope and 'single-epitope' surfaces were then
      compared. For all antibody pairs tested, bi-epitope surfaces exhibited an ~ 10
      100-fold improvement in apparent binding affinities when compared with single
      epitope ones. When pairing 2 antibodies of low intrinsic binding affinities (~
      10(-8) M) and fast dissociation rates (~ 10(-2) s(-1)), the apparent binding
      affinity and dissociation rate of the bi-epitope surface was improved up to ~ 10(
      10) M and 10(-4) s(-1), respectively. This led to an ~ 100-200-fold enhancement
      in EphA2 limit of detection in crude cell supernatants. Our results show that the
      use of antibody mixtures in SPR applications constitutes a powerful approach to
      develop sensitive immunoassays, as previously shown for non-SPR formats. As SPR
      based assays have significantly expanded their reach in the last decade, such an
      approach promises to further accelerate their development.

PMID- 25372292
TI  - Spinal fMRI reveals decreased descending inhibition during secondary mechanical
      hyperalgesia.
AB  - Mechanical hyperalgesia is one distressing symptom of neuropathic pain which is
      explained by central sensitization of the nociceptive system. This sensitization
      can be induced experimentally with the heat/capsaicin sensitization model. The
      aim was to investigate and compare spinal and supraspinal activation patterns of
      identical mechanical stimulation before and after sensitization using functional
      spinal magnetic resonance imaging (spinal fMRI). Sixteen healthy subjects (6
      female, 10 male, mean age 27.2 +/- 4.0 years) were investigated with mechanical
      stimulation of the C6 dermatome of the right forearm during spinal fMRI. Testing
      was always performed in the area outside of capsaicin application (i.e. area of
      secondary mechanical hyperalgesia). During slightly noxious mechanical
      stimulation before sensitization, activity was observed in ipsilateral
      dorsolateral pontine tegmentum (DLPT) which correlated with activity in
      ipsilateral spinal cord dorsal gray matter (dGM) suggesting activation of
      descending nociceptive inhibition. During secondary mechanical hyperalgesia,
      decreased activity was observed in bilateral DLPT, ipsilateral/midline rostral
      ventromedial medulla (RVM), and contralateral subnucleus reticularis dorsalis,
      which correlated with activity in ipsilateral dGM. Comparison of voxel-based
      activation patterns during mechanical stimulation before/after sensitization
      showed deactivations in RVM and activations in superficial ipsilateral dGM. This
      study revealed increased spinal activity and decreased activity in supraspinal
      centers involved in pain modulation (SRD, RVM, DLPT) during secondary mechanical
      hyperalgesia suggesting facilitation of nociception via decreased endogenous
      inhibition. Results should help prioritize approaches for further in vivo studies
      on pain processing and modulation in humans.

PMID- 25372294
TI  - Male-biased predation and its effect on paternity skew and life history in a
      population of common brushtail possums (Trichosurus vulpecula).
AB  - Differences in predation risk may exert strong selective pressures on life
      history strategies of populations. We investigated the potential for predation to
      shape male mating strategies in an arboreal folivore, the common brushtail possum
      (Trichosurus vulpecula Kerr). We predicted that possums in a tropical population
      exposed to high natural levels of predation would grow faster and reproduce
      earlier compared to those in temperate populations with lower predation. We
      trapped a population of possums in eucalypt woodland in northern Australia each
      month to measure life history traits and used microsatellites to genotype all
      individuals and assign paternity to all offspring. We observed very high levels
      of male-biased predation, with almost 60% of marked male possums being eaten by
      pythons, presumably as a result of their greater mobility due to mate-searching.
      Male reproductive success was also highly skewed, with younger, larger males
      fathering significantly more offspring. This result contrasts with previous
      studies of temperate populations experiencing low levels of predation, where
      older males were larger and the most reproductively successful. Our results
      suggest that in populations exposed to high levels of predation, male possums
      invest in increased growth earlier in life, in order to maximise their mating
      potential. This strategy is feasible because predation limits competition from
      older males and means that delaying reproduction carries a risk of failing to
      reproduce at all. Our results show that life histories are variable traits that
      can match regional predation environments in mammal species with widespread
      distributions. 

PMID- 25372293
TI  - Caspase-1/ASC inflammasome-mediated activation of IL-1beta-ROS-NF-kappaB pathway
      for control of Trypanosoma cruzi replication and survival is dispensable in NLRP3
      /- macrophages.
AB  - In this study, we have utilized wild-type (WT), ASC-/-, and NLRP3-/- macrophages
      and inhibition approaches to investigate the mechanisms of inflammasome
      activation and their role in Trypanosoma cruzi infection. We also probed human
      macrophages and analyzed published microarray datasets from human fibroblasts,
      and endothelial and smooth muscle cells for T. cruzi-induced changes in the
      expression genes included in the RT Profiler Human Inflammasome arrays. T. cruzi
      infection elicited a subdued and delayed activation of inflammasome-related gene
      expression and IL-1beta production in mphis in comparison to LPS-treated
      controls. When WT and ASC-/- macrophages were treated with inhibitors of caspase
      1, IL-1beta, or NADPH oxidase, we found that IL-1beta production by caspase-1/ASC
      inflammasome required reactive oxygen species (ROS) as a secondary signal.
      Moreover, IL-1beta regulated NF-kappaB signaling of inflammatory cytokine gene
      expression and, subsequently, intracellular parasite replication in macrophages.
      NLRP3-/- macrophages, despite an inability to elicit IL-1beta activation and
      inflammatory cytokine gene expression, exhibited a 4-fold decline in
      intracellular parasites in comparison to that noted in matched WT controls. NLRP3
      /- macrophages were not refractory to T. cruzi, and instead exhibited a very high
      basal level of ROS (>100-fold higher than WT controls) that was maintained after
      infection in an IL-1beta-independent manner and contributed to efficient parasite
      killing. We conclude that caspase-1/ASC inflammasomes play a significant role in
      the activation of IL-1beta/ROS and NF-kappaB signaling of cytokine gene
      expression for T. cruzi control in human and mouse macrophages. However, NLRP3
      mediated IL-1beta/NFkappaB activation is dispensable and compensated for by ROS
      mediated control of T. cruzi replication and survival in macrophages. 

PMID- 25372295
TI  - KCNJ10 may not be a contributor to nonsyndromic enlargement of vestibular
      aqueduct (NSEVA) in Chinese subjects.
AB  - BACKGROUND: Nonsyndromic enlargement of vestibular aqueduct (NSEVA) is an
      autosomal recessive hearing loss disorder that is associated with mutations in
      SLC26A4. However, not all patients with NSEVA carry biallelic mutations in
      SLC26A4. A recent study proposed that single mutations in both SLC26A4 and KCNJ10
      lead to digenic NSEVA. We examined whether KCNJ10 excert a role in the
      pathogenesis of NSEVA in Chinese patients. METHODS: SLC26A4 was sequenced in 1056
      Chinese patients with NSEVA. KCNJ10 was screened in 131 patients who lacked
      mutations in either one or both alleles of SLC26A4. Additionally, KCNJ10 was
      screened in 840 controls, including 563 patients diagnosed with NSEVA who carried
      biallelic SLC26A4 mutations, 48 patients with nonsyndromic hearing loss due to
      inner ear malformations that did not involve enlargement of the vestibular
      aqueduct (EVA), 96 patients with conductive hearing loss due to various causes,
      and 133 normal-hearing individuals with no family history of hereditary hearing
      loss. RESULTS: 925 NSEVA patients were found carrying two-allele pathogenic
      SLC26A4 mutations. The most frequently detected KCNJ10 mutation was c.812G>A
      (p.R271H). Compared with the normal-hearing control subjects, the occurrence rate
      of c.812G>A in NSEVA patients with lacking mutations in one or both alleles of
      SLC26A4 had no significant difference(1.53% vs. 5.30%, chi(2) = 2.798, p =
      0.172), which suggested that it is probably a nonpathogenic benign variant.
      KCNJ10 c.1042C>T (p.R348C), the reported EVA-related mutation, was not found in
      patients with NSEVA who lacked mutations in either one or both alleles of
      SLC26A4. Furthermore, the normal-hearing parents of patients with NSEVA having
      two SLC26A4 mutations carried the KCNJ10 c.1042C>T or c.812G>A mutation and a
      SLC26A4 pathogenic mutation. CONCLUSION: SLC26A4 is the major genetic cause in
      Chinese NSEVA patients, accounting for 87.59%. KCNJ10 may not be a contributor to
      NSEVA in Chinese population. Other genetic or environmental factors are possibly
      play a role in the etiology of Chinese EVA patients with zero or monoallelic
      SLC26A4 mutation.

PMID- 25372296
TI  - The asymmetric total synthesis of cinbotolide: a revision of the original
      structure.
AB  - The structure 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide (1) was assigned to
      a metabolite of Botrytis cinerea, but the spectra of several synthetic analogues
      had significant differences from that of 1. Examination of the constituents of a
      B. cinerea mutant that overproduces polyketides gave sufficient quantities of 1,
      now named cinbotolide, for chemical transformations. These led to a revised gamma
      butyrolactone structure for the metabolite. This structure has been confirmed by
      an asymmetric total synthesis, which also established its absolute configuration.

PMID- 25372297
TI  - The room temperature electrochemical synthesis of N-doped graphene and its
      electrocatalytic activity for oxygen reduction.
AB  - We report a facile and green electrochemical method using graphene oxide as the
      precursor to synthesize nitrogen doped graphene at room temperature in ammonia
      containing aqueous solution. The nitrogen doping content reaches 3.3 at%, and the
      resultant NG shows excellent activity toward the oxygen reduction reaction. 

PMID- 25372298
TI  - How morphology and surface crystal texture affect thermal stability of a metallic
      nanoparticle: the case of silver nanobelts and pentagonal silver nanowires.
AB  - Thermal instability of metallic nanoparticles is typically attributed to chemical
      attack by contaminants. However, thermodynamic stability is independent of other
      affecting parameters. The importance of this will be clarified when the
      structural change toward a more stable thermodynamic condition may be followed by
      a chemical reaction with the surroundings, which may cause a wrong diagnosis. In
      this research, molecular dynamics simulations and experimental observations were
      performed to investigate the effect of crystallography and surface texture on
      stability at high temperature using two closely related model nanoparticles:
      silver nanobelts and pentagonal nanowires. Previously, the instability of silver
      nanowires was associated with sulfidation of the wire at high temperature.
      However, we found that the silver nanowires are inherently unstable at high
      temperature, degrading due to the high-energy nature of the nanowire's
      predominately (100) crystallographic surface and pentagonal geometry. In
      contrast, the silver nanobelts resist thermal degradation up to 500  degrees C
      because of their predominately low-energy (111) crystallographic surfaces. In
      this case study, we successfully demonstrate that inherent thermodynamic
      stability driven by morphology is significant in metallic nanoparticles, and
      should be investigated when selecting a nanoparticle for high temperature
      applications. Moreover, we identify a new one-dimensional nanoparticle, the
      silver nanobelt, with inherent high-temperature stability. 

PMID- 25372300
TI  - Nanostructure of [Li(G4)] TFSI and [Li(G4)] NO3 solvate ionic liquids at HOPG and
      Au(111) electrode interfaces as a function of potential.
AB  - Atomic force microscopy (AFM) force measurements have been used to study the
      solvate ionic liquid (IL) double layer nanostructure at highly ordered pyrolytic
      graphite (HOPG) and Au(111) electrode surfaces as a function of potential. Two
      solvate ILs are investigated, [Li(G4)] TFSI and [Li(G4)] NO3. Normal force versus
      apparent separation data indicates that both solvate ILs adopt a multilayered
      morphology at the electrode interface, similar to conventional ILs. Calculations
      of adsorption free energies indicate that at 0 V the ion layer in contact with
      the electrode surface is enriched in the more surface active cations. When a
      positive or negative surface bias is applied, the concentration of counterions in
      the innermost layer increases, and higher push-through forces are required to
      displace near surface layers, indicating a stronger interfacial structure.
      Generally, [Li(G4)] TFSI has a better defined structure than [Li(G4)] NO3 on both
      electrode surfaces due to stronger cohesive interactions within layers.
      Interfacial structure is also better defined for both solvate ILs on HOPG than
      Au(111) due to the greater surface roughness of Au(111). Further, at all negative
      potentials on both surfaces, a small final step is observed, consistent with
      either compression of the complex cation adsorbed structure or desolvation of the
      glyme from the Li(+). 

PMID- 25372299
TI  - Liver fibrosis progression despite HCV cure with antiviral therapy in HIV-HCV
      coinfected patients.
AB  - BACKGROUND: Accelerated liver fibrosis and more frequent hepatic decompensation
      events and liver-related deaths are characteristically seen in chronic hepatitis
      C patients coinfected with HIV compared with HCV-monoinfected individuals.
      Quantitative estimates of long-term clinical benefits derived from curing HCV
      with antiviral therapy in coinfected patients are scarce, despite being needed
      for accurate cost-effectiveness decisions using expensive direct-acting
      antivirals in this population. METHODS: We retrospectively examined all HIV-HCV
      coinfected patients followed at one reference clinic in Madrid since 2004. Liver
      fibrosis was measured longitudinally using elastometry; changes above 30% in
      kilopascal units were considered as significant. RESULTS: A total of 568 HIV-HCV
      coinfected patients were examined. Pegylated interferon/ribavirin therapy had
      been given to 396 (69.7%) of whom 138 (34.8%) had achieved sustained virological
      response (SVR). Mean follow-up was of 6.8 (+/-1.5) years for hepatic events and
      4.4 (+/-0.8) years for liver fibrosis. Hepatic decompensation events, liver
      related deaths and significant liver fibrosis progression occurred less
      frequently in SVR than in non-treated/treatment failures. Although regression of
      liver fibrosis occurred in most SVR patients, fibrosis significantly progressed
      in 7.2% of them, in association with higher plasma HIV RNA (P=0.005) and longer
      exposure to HIV protease inhibitors (P=0.009). CONCLUSIONS: Achievement of SVR
      dramatically reduces the risk of hepatic decompensation events and liver-related
      deaths in HIV-HCV-coinfected patients. Although liver fibrosis generally improves
      following HCV cure, worsening may occur in association with uncontrolled HIV
      replication and prolonged exposure to protease inhibitors. Thus, periodic
      assessment of liver fibrosis is warranted after SVR and screening for liver
      cancer should continue in coinfected patients with advanced liver fibrosis.

PMID- 25372301
TI  - [Colorectal Carcinoma with Suspected Lynch Syndrome: A Multidisciplinary
      Algorithm].
AB  - Lynch syndrome is the most frequent hereditary cancer syndrome, accounting for
      approximately 3-5 % of all colorectal cancers. In addition, it is the most
      frequent predisposing hereditary cause of endometrial cancer and is also
      associated with gastric cancer, ovarian cancer, cancer of the urinary tract as
      well as several other cancers. In clinical practise Lynch syndrome is frequently
      not detected and many clinicians admit uncertainties regarding diagnostic
      procedures. Also, counselling of patients is considered difficult regarding
      therapeutic - especially prophylactic surgical and chemopreventive options and
      recommendations. Based on a review of available literature we discuss optimized
      strategies for improved detection of suspected Lynch syndrome patients. The aim
      of this review is to establish a clinical algorithm of how to proceed on a
      diagnostic level and to discuss surgical options at the time of a colorectal
      cancer. In order to identify patients with Lynch syndrome, family history should
      be ascertained and evaluated in regards to fulfilment of the Amsterdam-II- and/or
      the revised Bethesda criteria. Subsequently immunohistochemical staining for the
      mismatch-repair-genes, BRAF testing for MLH1 loss of expression, as well as
      testing for microsatellite instability in some, followed by genetic counselling
      and mutation analysis when indicated, is recommended. Pathological identification
      of suspected Lynch syndrome is readily feasible and straightforward. However, the
      need of performing these analyses in the tumor biopsy at the time of
      (gastroenterological) diagnosis of CRC neoplasia is essential, in order to offer
      patients the option of a prophylactically extended surgery and - as recommended
      in the German S3 guidelines - to discuss the option of a merely prophylactical
      hysterectomy and oophorectomy (if postmenopausal) in women. Close cooperation
      between gastroenterologists, pathologists and surgeons is warranted, so that
      patients may benefit from options of extended or prophylactically extended
      surgery at the time of diagnosis of a colorectal primary. Patients nowadays must
      be involved in informed decision-making regarding prophylactic or extended
      prophylactic surgery at the time of a colorectal primary. To date, however,
      limitations in daily clinical practise, the failure to assess family history and
      the lack of awareness of this important hereditary syndrome is the major asset
      leading to severe underdiagnosis and putting to risk the indexpatients themselves
      and their families to (metachronous) CRC and the associated extracolonic cancers.
      If at all tumors of patients fulfilling Bethesda criteria will be analysed for
      MSI in the surgical specimen and therefore Lynch syndrome patients are not given
      the opportunity to opt for extended surgery. In clinical experience the
      postoperative MSI-analysis is inconsistently performed - even if the Bethesda
      criteria are fulfilled - and in case of suspected Lynch syndrome genetically
      counselling is not consistently recommended. Therefore affected cancer patients
      are left unaware of their increased genetic risk and in average 3 high-risk gene
      carriers per family miss the opportunity to actively engage in the recommended
      screening program. 

PMID- 25372302
TI  - Cytochrome P450-mediated bioactivation of mefenamic acid to quinoneimine
      intermediates and inactivation by human glutathione S-transferases.
AB  - Mefenamic acid (MFA) has been associated with rare but severe cases of
      hepatotoxicity, nephrotoxicity, gastrointestinal toxicity, and hypersensitivity
      reactions that are believed to result from the formation of reactive metabolites.
      Although formation of protein-reactive acylating metabolites by phase II
      metabolism has been well-studied and proposed to be the cause of these toxic side
      effects, the oxidative bioactivation of MFA has not yet been competely
      characterized. In the present study, the oxidative bioactivation of MFA was
      studied using human liver microsomes (HLM) and recombinant human P450 enzymes. In
      addition to the major metabolite 3'-OH-methyl-MFA, resulting from the benzylic
      hydroxylation by CYP2C9, 4'-hydroxy-MFA and 5-hydroxy-MFA were identified as
      metabolites resulting from oxidative metabolism of both aromatic rings of MFA. In
      the presence of GSH, three GSH conjugates were formed that appeared to result
      from GSH conjugation of the two quinoneimines formed by further oxidation of 4'
      hydroxy-MFA and 5-hydroxy-MFA. The major GSH conjugate was identified as 4'-OH-5'
      glutathionyl-MFA and was formed at the highest activity by CYP1A2 and to a lesser
      extent by CYP2C9 and CYP3A4. Two minor GSH conjugates resulted from secondary
      oxidation of 5-hydroxy-MFA and were formed at the highest activity by CYP1A2 and
      to a lesser extent by CYP3A4. Additionally, the ability of seven human
      glutathione S-transferases (hGSTs) to catalyze the GSH conjugation of the
      quinoneimines formed by P450s was also investigated. The highest increase of
      total GSH conjugation was observed with hGSTP1-1, followed by hepatic hGSTs
      hGSTA2-2 and hGSTM1-1. The results of this study show that, next to phase II
      metabolites, reactive quinoneimines formed by oxidative bioactivation might also
      contribute to the idiosyncratic toxicity of MFA.

PMID- 25372303
TI  - Electrochemical properties of metal-oxide-coated carbon electrodes prepared by
      atomic layer deposition.
AB  - Here we report on the electrochemical properties of carbon electrodes coated with
      thin layers of Al2O3 and SnO2. These oxide films were deposited using atomic
      layer deposition (ALD) and range in thickness from 1 to 6 nm. Electrochemical
      experiments show that the thinnest oxide layers contain defects that penetrate to
      the underlying carbon electrode. However, oxygenation of the carbon surface prior
      to ALD increases the surface concentration of nucleation sites for oxide growth
      and suppresses the defect density. Films of Al2O3 just ~3-4 nm in thickness are
      free of pinholes. Slightly thicker coatings of SnO2 are required for equivalent
      passivation. Both Al2O3 and SnO2 films are stable in both neutral and acidic
      electrolytes even after repeated voltammetric scanning. The results reported here
      open up the possibility of studying the effect of oxide supports on
      electrocatalytic reactions. 

PMID- 25372304
TI  - Fabrication of nanocapsule carriers from multilayer-coated vaterite calcium
      carbonate nanoparticles.
AB  - Nanosized luminescent sensors were prepared as reagents for optical sensing and
      imaging of oxygen using ratiometric emission properties of a two-dye system.
      Polymeric capsules were fabricated utilizing poly(vinylsulfonic acid) (PVSA)
      stabilized vaterite CaCO3 nanoparticles (CCNPs) as sacrificial templates. The
      buffer and polymeric surfactant requirements of the layer-by-layer (LbL) process
      were evaluated toward deposition of multilayer coatings and, ultimately,
      formation of hollow capsules using these interesting materials. CCNPs were found
      to be more stable in alkaline NaHCO3 buffer after repeated cycles of washing
      under sonication and resuspension. An intermediate PVSA concentration was
      required to maximize the loading of oxygen-sensitive porphyrin and oxygen
      insensitive fluorescent nanoparticles in the CCNPs while maintaining minimal
      nanoparticle size. The CCNPs were then coated with polyelectrolyte multilayers
      and subsequent removal of the CaCO3 core yielded nanocapsules containing dye and
      fluorescent nanoparticles. The resulting nanocapsules with encapsulated
      luminophores functioned effectively as oxygen sensors with a quenching response
      of 89.28 +/- 2.59%, and O2 (S = 1/2) = 20.91 MUM of dissolved oxygen.

PMID- 25372305
TI  - Screening young adults for nonhereditary colorectal cancer.

PMID- 25372306
TI  - Medicare's prospective payment system: A critical appraisal.
AB  - Implementation of the Medicare prospective payment system (PPS) for hospital
      payment has produced major changes in the hospital industry and in the way
      hospital services are used by physicians and their patients. The substantial
      published literature that examines these changes is reviewed in this article.
      This literature suggests that most of the intended effects of PPS on costs and
      intensity of care have been realized. But the literature fails to answer
      fundamental questions about the effectiveness and equity of administered pricing
      as a policy tool for cost containment. The literature offers some hope that the
      worst fears about the effects of PPS on quality of care and the health of the
      hospital industry have not materialized. But because of data lags, the studies
      done to date seem to tell us more about the effects of the early, more generous
      period of PPS than about the opportunity costs of reducing hospital cost
      inflation.

PMID- 25372308
TI  - An expanding universe of mRNA modifications.

PMID- 25372309
TI  - PARP1 and CBP lose their footing in cancer.

PMID- 25372311
TI  - Resorcylic acid lactone biosynthesis relies on a stereotolerant macrocyclizing
      thioesterase.
AB  - Zearalenone and radicicol are highly related resorcylic acid lactones with the
      rare property of having opposite stereochemical configurations of the secondary
      alcohol involved in lactone formation. The ability of the thioesterases from the
      zearalenone and radicicol biosynthetic pathways to macrocyclize both D and L
      configured synthetic substrate analogs was biochemically characterized and showed
      that both enzymes were highly stereotolerant, macrocyclizing both substrates with
      similar kinetic parameters. This observed stereotolerance is consistent with a
      proposed evolution of both natural products from a common ancestral resorcylic
      acid lactone.

PMID- 25372312
TI  - Implementation of the forward-reverse method for calculating the potential of
      mean force using a dynamic restraining protocol.
AB  - We present a new sampling and analysis scheme for calculating the potential of
      mean force (PMF) of systems studied by steered molecular dynamics simulations.
      This scheme, which we call the bin-passing method, is based on the forward
      reverse (FR) method (due to I. Kosztin and co-workers, Kosztin et al. J. Chem.
      Phys. 2006, 124(6), 064106) and arguments based on the second law of
      thermodynamics. Applying the bin-passing method results in enhanced sampling,
      better separation of the reversible and irreversible work distributions, and
      faster convergence to the underlying PMF of the system under study. Post
      simulation analysis is performed using a purpose-built software that we have made
      publicly available at https://github.com/1particle/bin-passing_analyzer under the
      terms of the GNU General Public License (version 3). Three examples are provided,
      for systems of varying sizes and complexities, to demonstrate the efficiency of
      this method and the quality of the results: for the dissociation PMF of NaCl in
      water, the bin-passing method obtains PMFs in excellent agreement with that
      obtained for the same system and using the same force-field through static
      (equilibrium) methods. The bin-passing method gives a very symmetric PMF for
      passage of a single water molecule through a DPPC bilayer, and the resultant PMF
      leads to permeability values in better agreement with experiments than those
      obtained through previous simulation studies. Finally, we consider the
      interaction of the antimicrobial peptide HHC-36 with two model membranes and
      employ the bin-passing method to obtain the PMFs for peptide adsorption to the
      membranes. The characteristics of these PMFs are consistent with the qualities
      established for the HHC-36 peptide through in vivo and in vitro experiments, as a
      non-toxic strong antimicrobial agent. 

PMID- 25372310
TI  - DNA methylation: old dog, new tricks?
AB  - DNA methylation is an epigenetic modification that is generally associated with
      repression of transcription initiation at CpG-island promoters. Here we argue
      that, on the basis of recent high-throughput genomic and proteomic screenings,
      DNA methylation can also have different outcomes, including activation of
      transcription. This is evidenced by the fact that transcription factors can
      interact with methylated DNA sequences. Furthermore, in certain cellular
      contexts, genes containing methylated promoters are highly transcribed.
      Interestingly, this uncoupling between methylated DNA and repression of
      transcription seems to be particularly evident in germ cells and pluripotent
      cells. Thus, contrary to previous assumptions, DNA methylation is not exclusively
      associated with repression of transcription initiation. 

PMID- 25372313
TI  - Treatment of keratosis pilaris with 810-nm diode laser: a randomized clinical
      trial.
AB  - IMPORTANCE: Keratosis pilaris (KP) is a common skin disorder of follicular
      prominence and erythema that typically affects the proximal extremities, can be
      disfiguring, and is often resistant to treatment. Shorter-wavelength vascular
      lasers have been used to reduce the associated erythema but not the textural
      irregularity. OBJECTIVE: To determine whether the longer-wavelength 810-nm diode
      laser may be effective for treatment of KP, particularly the associated skin
      roughness/bumpiness and textural irregularity. DESIGN, SETTING, AND PARTICIPANTS:
      We performed a split-body, rater-blinded, parallel-group, balanced (1:1), placebo
      controlled randomized clinical trial at a dermatology outpatient practice of an
      urban academic medical center from March 1 to October 1, 2011. We included all
      patients diagnosed as having KP on both arms and Fitzpatrick skin types I through
      III. Of the 26 patients who underwent screening, 23 met our enrollment criteria.
      Of these, 18 patients completed the study, 3 were lost to or unavailable for
      follow-up, and 2 withdrew owing to inflammatory hyperpigmentation after the laser
      treatment. INTERVENTIONS: Patients were randomized to receive laser treatment on
      the right or left arm. Each patient received treatment with the 810-nm pulsed
      diode laser to the arm randomized to be the treatment site. Treatments were
      repeated twice, for a total of 3 treatment visits spaced 4 to 5 weeks apart. MAIN
      OUTCOMES AND MEASURES: The primary outcome measure was the difference in disease
      severity score, including redness and roughness/bumpiness, with each graded on a
      scale of 0 (least severe) to 3 (most severe), between the treated and control
      sites. Two blinded dermatologists rated the sites at 12 weeks after the initial
      visit. RESULTS: At follow-up, the median redness score reported by the 2 blinded
      raters for the treatment and control sides was 2.0 (interquartile range [IQR], 1
      2; P = .11). The median roughness/bumpiness score was 1.0 (IQR, 1-2) for the
      treatment sides and 2.0 (IQR, 1-2) for the control sides, a difference of 1 (P =
      .004). The median overall score combining erythema and roughness/bumpiness was
      3.0 (IQR, 2-4) for the treatment sides and 4.0 (IQR, 3-5) for the control sides,
      a difference of 1 (P = .005). CONCLUSIONS AND RELEVANCE: Three treatments with
      the 810-nm diode laser may induce significant improvements in skin texture and
      roughness/bumpiness in KP patients with Fitzpatrick skin types I through III, but
      baseline erythema is not improved. Complete treatment of erythema and texture in
      KP may require diode laser treatment combined with other laser or medical
      modalities that address redness. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01281644.

PMID- 25372314
TI  - Relationships Among Performance Measures for Medicare Managed Care Plans.
AB  - The Health Care Financing Administration (HCFA) has relied primarily on the
      Health Employer Data Information Set (HEDIS(r)), the Consumer Assessment of
      Health Plans Study (CAHPS(r)), and the Medicare Health Outcomes Survey (HOS) to
      track health plan performance. However, many relationships among these measures
      are unknown. We found significant relationships between four HEDIS(r) measures
      and many items in the CAHPS(r) measure as well as items in HOS concerning
      beneficiary general health ratings. Our study suggests that interpretation of
      performance data is improved by integrating access, effectiveness of care,
      beneficiary experience, health status, and risk measures into an analytic
      framework.

PMID- 25372315
TI  - The SEURAT-1 approach towards animal free human safety assessment.
AB  - SEURAT-1 is a European public-private research consortium that is working towards
      animal-free testing of chemical compounds and the highest level of consumer
      protection. A research strategy was formulated based on the guiding principle to
      adopt a toxicological mode-of-action framework to describe how any substance may
      adversely affect human health.The proof of the initiative will be in
      demonstrating the applicability of the concepts on which SEURAT-1 is built on
      three levels:(i) Theoretical prototypes for adverse outcome pathways are
      formulated based on knowledge already available in the scientific literature on
      investigating the toxicological mode-of-actions leading to adverse outcomes
      (addressing mainly liver toxicity);(ii)adverse outcome pathway descriptions are
      used as a guide for the formulation of case studies to further elucidate the
      theoretical model and to develop integrated testing strategies for the prediction
      of certain toxicological effects (i.e., those related to the adverse outcome
      pathway descriptions);(iii) further case studies target the application of
      knowledge gained within SEURAT-1 in the context of safety assessment. The
      ultimate goal would be to perform ab initio predictions based on a complete
      understanding of toxicological mechanisms. In the near-term, it is more realistic
      that data from innovative testing methods will support read-across arguments.
      Both scenarios are addressed with case studies for improved safety assessment. A
      conceptual framework for a rational integrated assessment strategy emerged from
      designing the case studies and is discussed in the context of international
      developments focusing on alternative approaches for evaluating chemicals using
      the new 21st century tools for toxicity testing.

PMID- 25372316
TI  - Circumpapillary choroidal hemorrhage masquerading as melanoma--enhanced depth
      imaging optical coherence tomography features.
AB  - PURPOSE: To illustrate the distinguishing findings of choroidal hemorrhage on
      enhanced depth imaging optical coherence tomography. METHODS: Case report.
      RESULTS: An 81-year-old man on a daily aspirin with well-controlled hypertension
      noted blurred visual acuity and was diagnosed with presumed choroidal melanoma
      based on the clinical appearance and generalized hyperfluorescence on
      angiography. Upon referral, visual acuity was 20/100 in the right eye and 20/30
      in the otherwise unremarkable left eye. Clinical examination revealed a choroidal
      mass of velvety-brown color with ill-defined margins, suggestive of hemorrhage.
      Ultrasonography disclosed a thin echogenic mass of 2.1 mm in thickness.
      Fluorescein angiography showed a hyperfluorescent mass with overlying
      hypofluorescent choroidal folds. Enhanced depth imaging optical coherence
      tomography revealed an irregular anterior contour of the choroid with small
      folds. Within the deep choroid was a featureless, optically empty region with a
      scalloped anterior margin pushing the choroid anteriorly and with shallow,
      scalloped lateral wings. These features were consistent with choroidal
      hemorrhage. On follow-up at 2 months, complete resolution of hemorrhage was
      noted. CONCLUSION: Choroidal hemorrhage can resemble choroidal melanoma.
      Differentiation depends on clinical features and diagnostic testing. Enhanced
      depth imaging optical coherence tomography shows a scalloped anterior border of
      the blood in the outer choroid that probably reflects clot contraction.

PMID- 25372317
TI  - Bilateral retinal detachment in Werner syndrome.
AB  - PURPOSE: To report the development of bilateral retinal detachment in a patient
      with Werner syndrome. METHODS: Retrospective chart review. A 44-year-old woman
      diagnosed with Werner syndrome developed bilateral retinal detachment. The fundus
      in both eyes showed patchy chorioretinal atrophy similar to that seen in high
      myopia, with the retinal detachment limited to the posterior pole. Two weeks
      after performing vitrectomy in the right eye, vitrectomy was performed in the
      left eye. RESULTS: After the surgeries, both retinas were reattached. During the
      surgeries, we observed an excessively liquefied vitreous and a posterior hyaloid
      membrane that was tightly attached to the retina. The retinal break was located
      along the superotemporal arcade and over an area of the patchy chorioretinal
      atrophy in both eyes. The chorioretinal atrophy and vitreous liquefaction
      appeared to be excessive for the patient's age and axial lengths (right: 26.66
      mm, left: 27.04 mm). CONCLUSION: Vitreoretinal changes found in this case might
      have been partially because of the premature aging associated with Werner
      syndrome.

PMID- 25372318
TI  - Choroidal metastases of choriocarcinoma.
AB  - PURPOSE: We present here a patient with choroidal metastases of choriocarcinoma;
      her clinical and pathologic findings are described. METHODS: Retrospective case
      study with fundus photographs. A 23-year-old woman presented with a dense
      vitritis, retinal detachment, and underlying chorioretinal lesions. Systemic
      workup revealed choriocarcinoma with disseminated metastases. RESULTS: This
      patient's underlying malignancy was unrecognized at initial presentation to
      ophthalmology. This case reaffirms the importance of thorough systemic
      investigation for atypical intraocular lesions. CONCLUSION: Adult intraocular
      neoplasms are most commonly metastases from distal primary malignancies. The same
      holds true for uveal malignancies. In many uveal malignancies, the intraocular
      lesion is a harbinger for an, as yet, undiscovered underlying systemic
      malignancy.

PMID- 25372319
TI  - Spectral domain optical coherence tomography findings in early deferoxamine
      maculopathy: report of two cases.
AB  - PURPOSE: To describe spectral domain optical coherence tomography features in two
      cases of early deferoxamine induced retinal toxicity. METHODS: Two patients
      complained of sudden bilateral visual loss and dyschromatopsia. Both suffered
      from acute myelocytic leukemia with severe aplastic anemia and were treated with
      intravenous deferoxamine for 1 month. First ophthalmologic exploration and follow
      up included fundoscopic examination, fluorescence angiography, fundus
      autofluorescence, and spectral domain optical coherence tomography. RESULTS:
      Initially, both patients presented with a decreased visual acuity, inferior to
      20/100. Fundus examination revealed a loss of transparency of the outer retina in
      the two cases. Autofluorescence pictures displayed hypoautofluorescence in the
      macular area, whereas fluorescein angiography unveiled an annular
      hyperfluorescence staining in the macular zone. Spectral domain optical coherence
      tomography showed a serous detachment of the neuroepithelium associated with
      photoreceptor outer segment elongation. Deferoxamine toxicity was immediately
      suspected and therapy promptly interrupted. One week later, both patients
      recovered visual acuity of 20/20 but retinal pigment epithelium (RPE) mottling
      was noticed in the macular areas. Spectral domain optical coherence tomography
      monitoring showed a progressive resolution of serous retinal detachment.
      Elongation of the photoreceptor outer segment disappeared but the RPE remained
      thickened, interrupted, and fragmented at different macular loci. CONCLUSION:
      Serous detachment of the neuroepithelium associated with photoreceptor outer
      segment elongation in the early stage of deferoxamine maculopathy is described
      for the first time. Early drug discontinuation allowed a fast resolution of the
      serous detachment but the typical RPE pigment mottling observed at the resolution
      phase was noticed 1 week later.

PMID- 25372320
TI  - Macular detachment associated with peripapillary detachment in pathologic myopia.
AB  - PURPOSE: To report a new spectral domain optical coherence tomography finding of
      retinal herniation in a patient with macular detachment accompanying
      peripapillary detachment in pathologic myopia. METHODS: Retrospective case
      report. A 47-year-old male patient with pathologic myopia and peripapillary
      detachment, pitlike defect, and associated macular detachment. RESULTS: Spectral
      domain optical coherence tomography scan showed intrachoroidal cavitation,
      discontinuity of retinal layers over the pitlike defect with herniation of
      retinal tissue through which communication between the choroidal cavity and
      subretinal space was seen. CONCLUSION: We report for the first time retinal
      herniation through pitlike dehiscence in pathologic myopia with intrachoroidal
      cavitation, and describe its association with macular detachment.

PMID- 25372321
TI  - Gemcitabine associated retinopathy and nephropathy.
AB  - PURPOSE: To report a case of presumed gemcitabine-induced retinopathy and
      nephropathy. METHODS: Case Report. Retrospective chart review. RESULTS: A 64-year
      old woman with a recent diagnosis of metastatic cholangiocarcinoma presented with
      progressive visual loss and renal failure shortly after the initiation of a
      chemotherapy regimen which included gemcitabine. Clinical examination and
      fluorescein angiography showed findings of severe retinal ischemia. CONCLUSION:
      Although gemcitabine chemotherapy has been reported to cause a Purtscher-like
      retinopathy, we propose in our patient a gemcitabine-induced vasculopathy that
      lead to significant retinal and renal ischemia.

PMID- 25372322
TI  - Temporal inferior vein submerging into intrachoroidal cavitation and gamma zone.
AB  - PURPOSE: To describe the appearance of the temporal inferior vein submerging into
      the parapapillary region with characteristics of parapapillary gamma zone and
      parapapillary beta zone. METHODS: Ophthalmoscopy in a 28-year-old man showed a
      sagittally rotated optic nerve head with marked temporal inferior parapapillary
      atrophy, in which the temporal inferior vein appeared to partially disappear.
      RESULTS: Serial optical coherence tomography images showed from inferior to
      superior, an intrachoroidal cavitation covered by intact Bruch membrane with
      retinal pigment epithelium (fulfilling the criteria of parapapillary beta zone).
      The intrachoroidal cavitation continued into an area with opened Bruch membrane
      (fulfilling the definition of parapapillary gamma zone) and a lamellar defect of
      the deep scleral layer. The lamellar defect became perforated leading to an
      apparent herniation of the retinal tissue into the almost extraocular space. From
      this herniation site, the inferior temporal vessel trunk submerged into an
      intrascleral or extrascleral pathway in the direction to the optic disk while the
      defect in the deep scleral layer was closed. Finally, more superior, the
      intrachoroidal cavitation decreased in volume and extent while Bruch membrane was
      absent (gamma zone). CONCLUSION: This report describes an unusual course of the
      inferior temporal vessel trunk and an associated unusual anatomy of the
      parapapillary region with beta zone and gamma zone, and an additional defect in
      the deep scleral layer allowing the exit of the temporal inferior vessel trunk
      into the extrascleral space. The illustration may also show the usefulness of the
      differentiation between beta zone and gamma zone in the parapapillary region.

PMID- 25372323
TI  - Nocardia asteroides subretinal abscess in patient with acute myelogenous leukemia
      after allogeneic stem cell transplant.
AB  - PURPOSE: Nocardia asteroides is the most common bacterial cause of subretinal
      abscesses; however, the diagnosis is often delayed because of the lack of
      suspicion leading to poor visual prognosis and possible enucleation. METHODS: A
      40-year-old man with a history of allogeneic stem cell transplant presents with
      decreased vision and a macular subretinal abscess. RESULTS: Examination revealed
      decreased vision at 20/100 with a peripapillary creamy subretinal lesion
      extending to the nasal margin of the fovea associated with intraretinal and
      subretinal hemorrhages without vitritis. Workup revealed disseminated N.
      asteroides, confirmed with a skin biopsy with the involvement of skin, eyes,
      lungs, and brain. Intravitreal amikacin and vancomycin were promptly given along
      with systemic vancomycin, sulfamethoxazole/trimethoprim, and meropenem. Vision
      improved rapidly to 20/40 with stabilization and eventual scarring of the lesion.
      CONCLUSION: This case illustrates that rapid diagnosis and treatment of
      subretinal N. asteroides can possibly have a good visual outcome and
      stabilization of the ocular manifestations.

PMID- 25372324
TI  - Unusual ocular injury by an acupuncture needle.
AB  - PURPOSE: To educate ophthalmologists on the potential dangers of periocular
      acupuncture and to describe an unusual mechanism of retinal injury. METHODS: A 42
      year-old woman who presented with blurred central vision and loss of peripheral
      vision. Her medical history was significant for hemifacial spasms related to a
      facial nerve injury, for which she had sought treatment. Clinical examination
      showed vertically oriented subretinal track measuring 12 mm in length, contiguous
      to the macula, with normal optic nerve appearance and foveal reflexes. Spectral
      domain optical coherence tomography showed a full-thickness perforation of the
      neurosensory retina at the inferior retinal arcade. Visual field testing 3 weeks
      after her injury showed 90% loss of her nasal hemifield. Electroretinography
      performed 8 weeks postinjury showed a 50% decrease in the right B-wave.
      Multifocal electroretinography showed a mild decrease in the recording of the
      right eye versus that of the left eye. CONCLUSION: Based on the history and
      clinical findings, the acupuncture needle penetrated the inferior globe and
      created a subretinal track. The particular location of the needle entry into the
      eye and the extreme malleability of the acupuncture needle created a long
      subretinal track. Ophthalmologists should be familiar with the ocular injuries
      caused by periocular acupuncture therapies.

PMID- 25372325
TI  - Subretinal migration of drusenoid material after a spontaneous retinal pigment
      epithelial tear.
AB  - PURPOSE: To describe the migration of drusen material through a retinal pigment
      epithelial (RPE) tear into the subretinal space. METHODS: Retrospective case
      report. CASE REPORT: A 71-year-old Asian male was diagnosed with an acquired
      vitelliform lesion overlying a drusenoid pigment epithelial detachment. A
      spontaneous RPE tear occurred. After the tear, optical coherence tomography
      showed the migration of drusenoid material through the RPE defect into the
      subretinal space. CONCLUSION: SubRPE drusenoid material may migrate into the
      subretinal space after a spontaneous RPE tear.

PMID- 25372326
TI  - Branch retinal artery occlusion secondary to prepapillary arterial loop.
AB  - PURPOSE: To report a case of branch retinal artery occlusion and prepapillary
      loop in a 10-year-old girl. METHODS: Case report with funduscopic and fluorescein
      angiography imaging. RESULTS: A 10-year-old girl presented with a history of the
      sudden onset of a superior visual field defect in her right eye. Fundus findings
      were consistent with thrombosis in a prepapillary arterial loop causing an
      inferior branch retinal artery occlusion. CONCLUSION: Bilateral congenital
      prepapillary vascular loops are rare, and are usually asymptomatic. However, they
      can be complicated by vitreous hemorrhage and thrombosis. Such thrombotic events
      may be precipitated by hemodynamic or intravascular changes associated with
      exercise.

PMID- 25372327
TI  - Fatal air embolism during endoresection of choroidal melanoma.
AB  - PURPOSE: To describe a case of intraoperative mortality because of air embolism
      during resection of a choroidal melanoma by pars plana vitrectomy. METHODS:
      Retrospective interventional case report. RESULTS: A 69-year-old man died
      unexpectedly at the time of pars plana vitrectomy. The operative technique
      involved the use of high-pressure air (60 mmHg) in the presence of traumatically
      exposed choroidal vasculature. Autopsy revealed a large air embolus in the right
      ventricle, which resulted in sudden cardiovascular collapse. CONCLUSION: Air
      embolism is a rare complication of ophthalmic surgery. Infusion of air in the
      presence of traumatically exposed choroidal vasculature exposes the patient to
      the risk of air embolism. Ophthalmic surgeons and anesthetists should be aware of
      the possibility of air embolism during certain ophthalmic procedures, and
      appropriate intraoperative monitoring should be considered.

PMID- 25372328
TI  - Choroidal findings in Bietti's crystalline dystrophy.
AB  - PURPOSE: To describe the choroidal findings in a patient with Bietti's
      crystalline dystrophy. METHODS: A 43-year-old woman with Bietti's crystalline
      dystrophy underwent a complete ophthalmologic examination including enhanced
      depth imaging spectral domain optical coherence tomography and en face optical
      coherence tomography. RESULTS: We observed a severe thinning of the choroid, 123
      MUm in the right eye and 110 MUm in the left eye. Crystal deposits were found not
      only in the retina but also in the choroid. En face optical coherence tomography
      clearly showed the intraretinal crystals as small hyperreflective dots in the
      different retinal layers and in the choroid. CONCLUSION: Our study gives new
      information on the aspect and the location of crystal deposits in the choroid and
      the abnormalities of the outer retina associated with the disease.

PMID- 25372329
TI  - Silicone oil microbubble found in failed full-thickness macular hole closure.
AB  - PURPOSE: To describe a case of failed macular hole closure after vitrectomy with
      silicone oil tamponade because of a silicone oil microbubble. METHODS: This is a
      retrospective case review of a single patient's clinical course. RESULTS: Because
      of the inability of the patient to assume a prone position after vitrectomy for
      full-thickness macular hole, 1000-centistoke silicone oil tamponade was used at
      the initial repair. Optical coherence tomography showed persistent full-thickness
      macular hole with evidence of a silicone oil microbubble within the macular hole.
      Subsequent vitrectomy with the removal of silicone oil and exchange for 25%
      sulfur hexafluoride (SF6) gas with attempted prone positioning failed to provide
      hole closure. Successful hole closure was accomplished after tamponade with 5000
      centistoke silicone oil, without prone positioning. No recurrence of the full
      thickness defect was seen after the eventual removal of 5000-centistoke silicone
      oil. CONCLUSION: It is possible that the silicone oil microbubble formation and
      migration within a full-thickness macular hole defect may contribute to surgical
      failure.

PMID- 25372330
TI  - Leaking choroidal nevus treated with focal laser photocoagulation.
AB  - PURPOSE: To present a case of leaky choroidal nevus that responded favorably to
      treatment with focal laser photocoagulation, shown by spectral domain optical
      coherence tomography, fundus autofluorescence, and fundus photography. METHODS:
      Descriptive case report of a 40-year-old male patient with decreased visual
      acuity because of subretinal fluid associated with a choroidal nevus, which was
      treated with focal laser photocoagulation. RESULTS: Treatment with focal laser
      photocoagulation to the surface of the choroidal nevus resulted in the resolution
      of subretinal fluid by 6 weeks. The therapeutic effect remained after 1 year of
      follow-up with continued improvement in vision and with no growth of the lesion.
      CONCLUSION: Laser photocoagulation can be an effective treatment for symptomatic
      subretinal fluid associated with a choroidal nevus. Spectral domain optical
      coherence tomography, fundus autofluorescence, and fundus photography can be
      helpful in monitoring the treatment response.

PMID- 25372331
TI  - Good visual outcome after repair of a very large macular hole with neurosensory
      retinal operculum.
AB  - PURPOSE: To describe a favorable outcome after the surgical repair of a very
      large macular hole with a neurosensory operculum. METHODS: Case report. A 42-year
      old man with a history of decreased vision for 3 months was found to have vision
      of 20/400, a very large macular hole (1159 MUm in diameter), and an operculum
      suspended on the posterior hyaloid above the hole. RESULTS: Vitrectomy and
      internal limiting membrane peel were performed. The operculum was processed for
      histology and found to contain neurons and glial cells. Fourteen months later,
      the patient's vision improved to 20/60. CONCLUSION: Very large macular holes have
      traditionally been considered to have a poor prognosis. Here, we demonstrate that
      such large holes can be repaired with good visual outcome, even in the setting of
      an operculum consisting of avulsed neural retina.

PMID- 25372332
TI  - Idiopathic multifocal choroiditis with peripapillary zonal inflammation: a
      multimodal imaging analysis.
AB  - PURPOSE: To report a case of idiopathic multifocal choroiditis with transient
      peripapillary zonal inflammation that was followed with multimodal imaging and
      explain the mechanism by which chorioretinal atrophy may occur. METHODS:
      Observational case report. Review of the clinical examination, ocular imaging,
      and progression of idiopathic multifocal choroiditis. RESULTS: A 30-year-old
      white myopic man presented with complaints of worsening vision and a loss of
      visual field for 1 month in his left eye. Using multimodal imaging, including
      wide-field imaging with fluorescein angiography, fundus autofluorescence, and
      high-definition spectral-domain optical coherence tomography, he was found to
      have a macula involving peripapillary zonal inflammation consistent with acute
      idiopathic multifocal choroiditis involving the outer photoreceptor layer,
      ellipsoid layer, retinal pigment epithelium, and choroid. This area of
      inflammation was monitored with multimodal imaging over 7 months and slowly
      improved along with the patient's vision. Imaging allowed us to view the
      development of chorioretinal scars from several, but not all, acute inflammatory
      white spots. CONCLUSION: Multifocal choroiditis is an inflammatory disorder
      affecting the outer photoreceptors, ellipsoid layer, retinal pigment epithelium,
      and choroid; and areas of acute inflammation may improve over time but can also
      leave permanent chorioretinal atrophy including focal lesions or peripapillary
      zonal atrophy.

PMID- 25372333
TI  - Combined CRVO with CRAO in a patient with protein C deficiency.
AB  - PURPOSE: To study the underlying factors in a young patient having central
      retinal venous obstruction with central retinal arterial obstruction and its
      effects on visual outcome. METHODS: A 33-year-old man presented with a complaint
      of sudden loss of vision in his right eye. A complete ophthalmic evaluation with
      fundus angiography showed combined central retinal venous obstruction with
      central retinal arterial obstruction. Detailed investigations revealed reduced
      (20%) functional assay of protein C suggestive of the diagnosis of severe Type II
      protein C deficiency with Factor V Leiden mutation. This ocular event was the
      first sign of the underlying disorder. RESULTS: The ophthalmic event rapidly
      progressed to no perception of light. Anticoagulant therapy was started to
      prevent life-threatening systemic complications. Despite antiglaucoma
      medications, intraocular pressure was high and cyclocryotherapy was advised.
      CONCLUSION: Retinal vascular disorders in the younger population have different
      underlying risk factors than in the older age group. Clinical presentation,
      severity, and management also depend on causative factors. Combined retinal
      artery and vein occlusion is very uncommon. Combined cases have mostly been
      attributed to rheological causes like thrombophilia, vessel wall inflammation,
      and mechanical compression. Protein C deficiency has mainly been linked to vein
      occlusions and there is no reference to protein C deficiency as a cause of
      combined central retinal venous obstruction and central retinal arterial
      obstruction. Combined cases usually present with severe visual loss and have
      rapid progression. Young patients having such presentation should be thoroughly
      evaluated to diagnose underlying factors and initiate appropriate management at
      the earliest.

PMID- 25372334
TI  - Retinal hemorrhages and intermediate uveitis in a patient with drug reaction with
      eosinophilia and systemic symptoms syndrome: a case report.
AB  - PURPOSE: To report a case of drug reaction (or rash) with eosinophilia and
      systemic symptoms syndrome in association with intraretinal hemorrhages and
      intermediate uveitis. METHODS: Single case report. RESULTS: A 22-year-old
      Hispanic woman developed a facial rash and blurry vision after the use of oral
      trimethoprim-sulfamethoxazole for a urinary tract infection. Fundus examination
      revealed bilateral +2 vitritis and intraretinal hemorrhages in all four
      quadrants. An oral mucosal biopsy revealed V-shaped coagulative necrosis,
      intraepithelial and superficial acute and lymphoplasmacytic inflammation,
      consistent with drug hypersensitivity reaction. CONCLUSION: Drug reaction (or
      rash) with eosinophilia and systemic symptoms syndrome can present as cutaneous
      rash, mucosal lesions, eosinophilia, intermediate uveitis, and intraretinal
      hemorrhages. In such cases, vitreoretinal manifestations may be considered as
      diagnostic criteria instead visceral involvement.

PMID- 25372335
TI  - Central serous chorioretinopathy after trabeculectomy in a patient with
      microphthalmos and congenital rubella syndrome.
AB  - PURPOSE: To describe a case of central serous chorioretinopathy after
      trabeculectomy surgery in an eye with microphthalmos in the setting of congenital
      rubella syndrome. METHODS: A Case report with color fundus photographs,
      fluorescein angiography, and spectral domain optical coherence tomography.
      RESULTS: A 46-year-old African American man, with a history of congenital heart
      disease and bilateral hearing loss, developed persistent vision loss in the left
      eye after trabeculectomy surgery. Ocular examination revealed bilateral salt-and
      pepper retinopathy and a serous detachment in the macula of the left eye.
      Fluorescein angiography showed an early "smoke-stack" pattern of
      hyperfluorescence with progressive filling of the subretinal space consistent
      with central serous chorioretinopathy. Spectral domain optical coherence
      tomography documented both size and extent of the serous retinal detachment and
      showed several pigment epithelial detachments. B-scan ultrasonography confirmed
      the serous retinal detachment on the left but showed no evidence of posterior eye
      wall thickening or of retrobulbar fluid. An A-scan revealed an axial length of
      21.8 mm on the right and 19.7 mm on left eye, confirming microphthalmos and
      supporting the suspected diagnosis of congenital rubella syndrome. CONCLUSION:
      Although uncommon, central serous chorioretinopathy can occur in anatomically
      small eyes after trabeculectomy surgery.

PMID- 25372336
TI  - Solvent vapour mediated spontaneous healing of self-organized defects of liquid
      crystal films.
AB  - Ultrathin liquid crystal films showed a nematic to isotropic transition when
      exposed to solvent vapour for a short duration while a reverse isotropic to
      nematic transition was observed when the film was isolated from the solvent
      exposure. The phase transitions were associated with the appearance and fading of
      surface patterns as the solvent molecules diffused into and out of the film
      matrix, resulting in the destruction or restoration of the orientational order. A
      long-time solvent vapour exposure caused the dewetting of the film on the
      surface, which was demonstrated by the formation of holes and their growth in
      size with the progress of time. Even at this stage, withdrawal of the solvent
      exposure produced an array of nematic fingers, which nearly self-healed the
      dewetted holes. The change in contact angle due to the phase transition coupled
      with the imbalance of osmotic pressure across the contact line due to the
      differential rate of solvent evaporation from the film and the hole helped the
      fingers to grow towards the centre of the hole. The appearance of the fingers
      upon withdrawal of the solvent exposure and their disappearance upon exposure to
      solvent were also found to be a nearly reversible process. These findings could
      significantly contribute to the development of vapour sensors and self-healing
      surfaces using liquid crystal thin films. 

PMID- 25372338
TI  - Overview.
AB  - This overview discusses articles published in this issue of the Health Care
      Financing Review, entitled "Measuring and Improving the Health Status of the
      Elderly, Poor, and Disabled." These articles focus on the following topics:
      Medicare beneficiaries with end stage renal disease (ESRD), children with
      disabilities, and persons with acquired immunodeficiency syndrome (AIDS).

PMID- 25372337
TI  - Statistical Validation of Surrogate Endpoints: Another Look at the Prentice
      Criterion and Other Criteria.
AB  - For the statistical validation of surrogate endpoints, an alternative formulation
      is proposed for testing Prentice's fourth criterion, under a bivariate normal
      model. In such a setup, the criterion involves inference concerning an
      appropriate regression parameter, and the criterion holds if the regression
      parameter is zero. Testing such a null hypothesis has been criticized in the
      literature since it can only be used to reject a poor surrogate, and not to
      validate a good surrogate. In order to circumvent this, an equivalence hypothesis
      is formulated for the regression parameter, namely the hypothesis that the
      parameter is equivalent to zero. Such an equivalence hypothesis is formulated as
      an alternative hypothesis, so that the surrogate endpoint is statistically
      validated when the null hypothesis is rejected. Confidence intervals for the
      regression parameter and tests for the equivalence hypothesis are proposed using
      bootstrap methods and small sample asymptotics, and their performances are
      numerically evaluated and recommendations are made. The choice of the equivalence
      margin is a regulatory issue that needs to be addressed. The proposed equivalence
      testing formulation is also adopted for other parameters that have been proposed
      in the literature on surrogate endpoint validation, namely, the relative effect
      and proportion explained. 

PMID- 25372340
TI  - Medicaid and the Health of Children.
AB  - The Medicaid program has evolved and expanded since its inception in 1965,
      providing health insurance coverage for ever-increasing numbers of children
      living in poverty. During the first 35 years of Medicaid, the program has
      expanded coverage to include preventive services for children, expanded
      eligibility criteria to include uninsured children not receiving welfare. The
      Medicaid program has encouraged innovation in the form of managed care and
      primary care case management. Most recently, the State Children's Health
      Insurance Program (SCHIP) has given States freedom in providing more children
      with coverage. Medicaid has had a powerful influence on the health of the
      Nation's children. Because of Medicaid coverage, fewer children die, and children
      have less severe illnesses, fewer hospitalizations, fewer emergency department
      visits, more preventive care, and more immunizations than they would have had
      they not been insured.

PMID- 25372341
TI  - Recent Innovations in Home Health Care Policy Research.
AB  - This overview discusses articles published in this issue of the Health Care
      Financing Review, entitled "Issues in Reforming Home Health Care." Articles focus
      on basic policy issues in the financing and delivery of home care services,
      illustrate how research provides insights into these issues, and report on some
      recent research and demonstration initiatives that are designed to further our
      understanding of how to improve the effectiveness and efficiency of home care
      services under Medicare and Medicaid.

PMID- 25372342
TI  - Overview.

PMID- 25372343
TI  - Home and Community-Based Services Waivers.
AB  - The history and current status of the Medicaid Home and Community-Based Services
      Waiver Program are presented. The article discusses the States' role in
      developing and implementing creative alternatives to institutional care for
      individuals who are Medicaid eligible. Also described are services that may be
      provided under the waiver program and populations served.

PMID- 25372345
TI  - MCBS Highlights: Barriers to Physician Care for Medicare Beneficiaries.

PMID- 25372344
TI  - Transplantation of purified autologous leukapheresis-derived CD34+ and CD133+
      stem cells for patients with chronic spinal cord injuries: long-term evaluation
      of safety and efficacy.
AB  - This study is aimed at describing a novel method for treating patients with
      chronic complete spinal cord injuries (SCIs) by utilizing autologous, purified
      CD34(+) and CD133(+) stem cells (SCs). The study focuses on the safety and
      efficacy of transplanting unmanipulated, autologous, purified stem cells in
      treated patients during a 5-year follow-up period. In this report, 19 patients
      were included (16 males and 3 females) who presented with a complete SCI (ASIA-A)
      in the thoracic region. The patients' endogenous cells were mobilized with
      subcutaneous granulocyte-colony-stimulating factor (G-CSF) for 5 days. We
      utilized the CliniMACS magnetic separation system to purify leukapheresis-derived
      CD34(+) and CD133(+) SCs. Purified SCs were directly transplanted into the SCI
      site. Patients were then monitored and followed for up to 5 years. On average, 76
      * 10(6) purified SCs were obtained from each patient, with 95.2% purity and >98%
      viability. SC transplantation into the cyst cavity or the subarachnoid space was
      successful and well tolerated in all 19 patients and did not cause any allergic
      or inflammatory reactions within the CNS in the early or late periods after
      transplantation. Ten patients (53%) showed no improvement after 42-60 months
      (ASIA-A), while seven patients (37%) demonstrated segmental sensory improvement
      (ASIA-B), and the remaining two patients (10%) had motor improvement (ASIA-C).
      This study presents a safe method for transplanting specific populations of
      purified autologous SCs that can be used to treat SCIs in a clinical setting. The
      results may be utilized as a stepping-stone for future investigations in the
      field of regenerative medicine for treatment of SCIs and other neurological
      diseases. This manuscript is published as part of the International Association
      of Neurorestoratology (IANR) special issue of Cell Transplantation. 

PMID- 25372346
TI  - How could haloalkaliphilic microorganisms contribute to biotechnology?
AB  - Haloalkaliphiles are microorganisms requiring Na(+) concentrations of at least
      0.5 mol.L(-1) and an alkaline pH of 9 for optimal growth. Their unique features
      enable them to make significant contributions to a wide array of biotechnological
      applications. Organic compatible solutes produced by haloalkaliphiles, such as
      ectoine and glycine betaine, are correlated with osmoadaptation and may serve as
      stabilizers of intracellular proteins, salt antagonists, osmoprotectants, and
      dermatological moisturizers. Haloalkaliphiles are an important source of
      secondary metabolites like rhodopsin, polyhydroxyalkanoates, and
      exopolysaccharides that play essential roles in biogeocycling organic compounds.
      These microorganisms also can secrete unique exoenzymes, including proteases,
      amylases, and cellulases, that are highly active and stable in extreme
      haloalkaline conditions and can be used for the production of laundry detergent.
      Furthermore, the unique metabolic pathways of haloalkaliphiles can be applied in
      the biodegradation and (or) biotransformation of a broad range of toxic
      industrial pollutants and heavy metals, in wastewater treatment, and in the
      biofuel industry.

PMID- 25372347
TI  - The actin cytoskeleton organization and disorganization properties of the
      photosynthetic dinoflagellate Symbiodinium kawagutii in culture.
AB  - The actin cytoskeleton organization in symbiotic marine dinoflagellates is
      largely undescribed; most likely, due to their intense pigment autofluorescence
      and cell walls that block fluorescent probe access. Using a freeze-fracture and
      fixation procedure, we observed the actin cytoskeleton of Symbiodinium kawagutii
      cultured in vitro with fluorescently labeled phalloidin and by indirect
      immunofluorescence with monoclonal antibodies specific for actin. The
      cytoskeleton appeared as an organized network with interconnected cortical and
      cytoplasmic thick filaments, along with some intertwined fine filaments. It
      showed a grid-type, reticular pattern organized in a lattice-like structure
      within the cell and throughout the cytoplasm. This organization was similar when
      the observations were done with either fluorescein isothiocyanate (FITC)
      phalloidin or anti-actin, although the latter showed a more evenly distributed
      fluorescence characteristic of nonpolymerized actin. The network organization
      collapsed upon treatment with latrunculin, resulting in bright foci and diffuse
      fluorescence. A similar effect was obtained upon butanedione monoxime treatment,
      except that no bright foci were observed. We have been able to successfully
      visualize the actin cytoskeleton of S. kawagutii cells using fluorescence-based
      procedures. This is the first report on the visualization of the organization of
      the actin cytoskeleton under various conditions in these walled, highly
      autofluorescent cells.

PMID- 25372348
TI  - Why Health Care Needs Design Research: Broadening the Perspective on
      Communication in Pediatric Care Through Play.
AB  - Today's pediatric health care lacks methods to tap into the emotional state of
      hospitalized pediatric patients (age 4-6 years). The most frequently used
      approaches were developed for adults and fail to acknowledge the importance of
      imaginary experiences and the notion of play that may appeal to children. The
      scope of this article is to introduce a new design-oriented method of gathering
      information about the emotional state of pediatric patients using an experimental
      computer game called the Child Patient game (CPgame). The CPgame was developed at
      a Danish hospital, and the results of the preliminary tests show that games could
      serve as a system in which children are willing to express their emotions through
      play. The results are based on two comparative analyses of the CPgame through
      which it is possible to identify three different types of players among the
      patients playing the game. Furthermore, the data reveal that pediatric patients
      display a radically different play pattern than children who are not in hospital.
      The inquiry takes an interdisciplinary approach; it has obvious health care
      related objectives and seeks to meet the urgent need for new methods within
      health care to optimize communication with young children. At the same time,
      design research (i.e., the development of new knowledge through the development
      of a new design) heavily impacts the method. 

PMID- 25372349
TI  - Effect of Low-Income Elderly Insurance Copayment Subsidies.
AB  - The authors use a two-part model of demand to model the impact of qualified
      Medicare beneficiary (QMB) enrollment on medical care use. Assuming QMB
      enrollment to be exogenous, they find Medicare Part B utilization to be 12
      percent higher and Part B expenditures 44 percent greater among QMBs than among
      eligible non-enrollees. There is no difference between these two groups in
      overall Part A expenditures. Modeling the possibility that QMB enrollment is
      endogenous, the authors find qualitatively similar results, but the estimates are
      not precisely estimated.

PMID- 25372350
TI  - MCBS Highlights: Racial and Ethnic Differences Among Medicare Beneficiaries.

PMID- 25372355
TI  - Determination of the persistence of dimetridazole, metronidazole and ronidazole
      residues in black tiger shrimp (Penaeus monodon) tissue and their stability
      during cooking.
AB  - The depletion of three banned nitroimidazole drugs - dimetridazole (DMZ),
      metronidazole (MNZ) and ronidazole (RNZ) - was investigated in black tiger shrimp
      (Penaeus monodon) following in-water medication. The highest concentrations of
      residues were measured immediately after the 24-h immersion (d0). At this time,
      MNZ and MNZ-OH residues were measured in shrimp tissue samples at concentrations
      ranging from 361 to 4189 and from 0.28 to 6.6 MUg kg(-1), respectively. DMZ and
      its metabolites HMMNI ranged in concentration between 31,509 and 37,780 and
      between 15.0 and 31.9 MUg kg(-1), respectively. RNZ and HMMNI concentrations
      ranged from 14,530 to 24,206 and from 25.0 to 55 MUg kg(-1), respectively. MNZ,
      DMZ and RNZ were the more persistent marker residues and can be detected for at
      least 8 days post-treatment. MNZ-OH was only detectable on d0 following treatment
      with MNZ. HMMNI residues were only detectable up to d1 (0.97-3.2 MUg kg(-1)) or
      d2 (1.2-4.5 MUg kg(-1)) following DMZ and RNZ treatment, respectively. The parent
      drugs MNZ, DMZ and RNZ were still measureable on d8 at 0.12-1.0, 40.5-55 and 8.8
      18.7 MUg kg(-1), respectively. The study also investigated the stability of
      nitroimidazole residues under various cooking procedures (frying, grilling,
      boiling, and boiling followed by microwaving). The experiments were carried out
      in shrimp muscle tissue containing both high and low concentrations of these
      residues. Different cooking procedures showed the impact on nitroimidazole
      residue concentration in shrimp tissue. Residue concentration depleted
      significantly, but partially, by boiling and/or microwaving, but the compounds
      were largely resistant to conventional grilling or frying. Cooking cannot
      therefore be considered as a safeguard against harmful nitroimidazole residues in
      shrimp.

PMID- 25372356
TI  - Health-Based Capitation Risk Adjustment in Minnesota Public Health Care Programs.
AB  - This article documents the history and implementation of health-based capitation
      risk adjustment in Minnesota public health care programs, and identifies key
      implementation issues. Capitation payments in these programs are risk adjusted
      using an historical, health plan risk score, based on concurrent risk assessment.
      Phased implementation of capitation risk adjustment for these programs began
      January 1, 2000. Minnesota's experience with capitation risk adjustment suggests
      that: (1) implementation can accelerate encounter data submission, (2)
      administrative decisions made during implementation can create issues that impact
      payment model performance, and (3) changes in diagnosis data management during
      implementation may require changes to the payment model.

PMID- 25372357
TI  - Hospital-based inpatient resource utilization associated with autosomal dominant
      polycystic kidney disease in the US.
AB  - OBJECTIVE: Polycystic kidney disease (PKD) is a clinically and genetically
      heterogeneous class of genetic disorders characterized by development of renal
      cysts leading to renal failure and end stage renal disease (ESRD). Autosomal
      dominant polycystic kidney disease (ADPKD) accounts for the majority of PKD cases
      and is the predominant monogenic cause of ESRD. Limited information on patient
      characteristics and healthcare resource utilization is available in this
      population. This study assessed hospital-based inpatient utilization of patients
      with ADPKD in the US to help further understand the disease, which may lead to
      treatments that delay progression and reduce healthcare resource utilization.
      METHODS: A cross-sectional analysis was conducted using MedAssets Health System
      Data to investigate inpatient resource utilization for a total of 1876 patients
      hospitalized with ADPKD or chronic kidney disease (CKD). Patient characteristics
      and inpatient resource utilization were compared between hospitalized patients
      with ADPKD and CKD, including demographic and clinical characteristics, overall
      health, rates of complications and surgical interventions, and average length of
      hospital and intensive care unit stay. RESULTS: Compared with patients with CKD,
      patients with ADPKD were more likely to have commercial insurance as their
      primary payer (36.1 vs 17.8%) and were significantly younger (mean age 57.9 vs
      69.5 years) and generally healthier (Charlson Comorbidity Score of 2.0 vs 3.3).
      Patients with ADPKD also had a substantially shorter average length of hospital
      stay (6.3 vs 10.3 days). However, patients with ADPKD experienced more kidney
      related complications and a higher surgical procedure rate (mainly for transplant
      and complete nephrectomy). CONCLUSIONS: Although patients with ADPKD were
      generally healthier than patients with CKD, specific kidney function
      complications were more frequent. Patients with ADPKD had a higher rate of major
      kidney procedures, which may contribute to the high burden of ADPKD-related
      hospital-based inpatient resource utilization.

PMID- 25372358
TI  - A new transgenic line reporting pStat3 signaling in glia.

PMID- 25372359
TI  - Overview: 40th Anniversary of Medicare and Medicaid.

PMID- 25372360
TI  - A peptide topological template for the dispersion of [60]fullerene in water.
AB  - Solubilization of [60]fullerene in water is a major challenge for biological and
      medical applications. To this purpose in this communication we describe for the
      first time a new dispersing system based on a peptide topological template. The
      presence of two carbobenzyloxy groups on the peptide side chains allows pi-pi
      interactions with [60]fullerene leading to the formation of stable supramolecular
      nanocomposites by means of mechanochemical methods. In particular, by high speed
      vibration milling colloidal dispersions (mean particle diameter 63 nm) containing
      up to 1.3 mg mL(-1) of [60]fullerene were obtained. Its presence in water was
      verified through UV-Vis and MALDI-TOF measurements, while its concentration was
      determined by thermogravimetric analysis. 

PMID- 25372362
TI  - Progression-free survival, patient-reported outcomes and the Holy Grail.
AB  - In oncology clinical trials, overall survival (OS) remains the gold standard for
      clinical beneft. However, because there are so many available treatment options
      for most types of cancer, survival analysis in clinical trials is often
      confounded by subsequent therapies. Progression-free survival (PFS) is an
      endpoint not so confounded, and one that requires fewer patients and less time to
      arrive at a conclusion about a new therapy. As a result, an ever-increasing
      number of oncology clinical trials are launched in which PFS is used as the
      primary endpoint. Several years ago, Pazdur emphasized that the time-to
      progression endpoint must use the same evaluation techniques and schedules for
      all treatment arms and he recommended blinding of trials or at minimum, the use
      of an external blinded radiographic review committee. He also noted that
      improvement in disease-related symptoms qualifes as clinical beneft and may
      therefore be an appropriate endpoint for drug approval. 

PMID- 25372361
TI  - Etched colloidal LiFePO4 nanoplatelets toward high-rate capable Li-ion battery
      electrodes.
AB  - LiFePO4 has been intensively investigated as a cathode material in Li-ion
      batteries, as it can in principle enable the development of high power
      electrodes. LiFePO4, on the other hand, is inherently "plagued" by poor
      electronic and ionic conductivity. While the problems with low electron
      conductivity are partially solved by carbon coating and further by doping or by
      downsizing the active particles to nanoscale dimensions, poor ionic conductivity
      is still an issue. To develop colloidally synthesized LiFePO4 nanocrystals (NCs)
      optimized for high rate applications, we propose here a surface treatment of the
      NCs. The particles as delivered from the synthesis have a surface passivated with
      long chain organic surfactants, and therefore can be dispersed only in aprotic
      solvents such as chloroform or toluene. Glucose that is commonly used as carbon
      source for carbon-coating procedure is not soluble in these solvents, but it can
      be dissolved in water. In order to make the NCs hydrophilic, we treated them with
      lithium hexafluorophosphate (LiPF6), which removes the surfactant ligand shell
      while preserving the structural and morphological properties of the NCs. Only a
      roughening of the edges of NCs was observed due to a partial etching of their
      surface. Electrodes prepared from these platelet NCs (after carbon coating)
      delivered a capacity of ~ 155 mAh/g, ~ 135 mAh/g, and ~ 125 mAh/g, at 1 C, 5 C,
      and 10 C, respectively, with significant capacity retention and remarkable rate
      capability. For example, at 61 C (10.3 A/g), a capacity of ~ 70 mAh/g was
      obtained, and at 122 C (20.7 A/g), the capacity was ~ 30 mAh/g. The rate
      capability and the ease of scalability in the preparation of these surface
      treated nanoplatelets make them highly suitable as electrodes in Li-ion
      batteries.

PMID- 25372363
TI  - Expanding the NCCN guidelines for distress management: a model of barriers to the
      use of coping resources.
AB  - Cancer-related distress impacts quality of care, resource use, and patient
      outcomes. Patients are increasingly screened for distress, yet many do not
      receive coping resources and psychosocial support services that may help to
      reduce their distress. Distress screening must be paired with attention to the
      different phases of the distress and coping process, with emphasis on barriers
      and facilitators of cancer patients' use of coping resources. This paper offers a
      conceptual model illustrating key pathways and modifying factors of distress and
      use of coping resources among cancer patients, and potential roles for cancer
      care providers and institutions in facilitating effective coping and distress
      reduction. Building on a review of relevant empirical and theoretical literature,
      we developed a conceptual model that integrates concepts from Stress and Coping
      Theory into the National Comprehensive Cancer Network's guidelines for Distress
      Management. We found that barriers and facilitating factors that may inhibit
      receipt of coping resources and services to reduce cancer-related distress
      include health and cancer beliefs, accessibility and acceptability, the role of
      caregivers in cancer treatment, coordination of care, and the quality of patient
      provider relationships. Herein, we highlight largely modifable factors that can
      infuence the successful uptake of coping resources and services to reduce
      distress among cancer patients. We conclude with recommendations for how cancer
      care providers and systems can better identify and address barriers to the use of
      distress reduction resources and support services. 

PMID- 25372364
TI  - Effects of exercise on disablement process model outcomes in prostate cancer
      patients undergoing androgen deprivation therapy.
AB  - BACKGROUND: Androgen-deprivation therapy (ADT) results in adverse physiologic,
      metabolic, and functional side effects that may accelerate functional limitations
      in patients with prostate cancer (PC). Although exercise improves muscular
      strength and functional performance, the extent to which exercise yields similar
      improvements in other disablement process outcomes in men on ADT has yet to be
      systematically evaluated. OBJECTIVE: To explore whether exercise results in
      comparable improvements in physiologic and structural body system impairment,
      functional limitation (relating to basic physical or mental actions), and
      physical disability domain outcomes identifed in the Disablement Process Model
      (DPM) in PC patients who are receiving ADT. METHODS: Data from studies of
      exercise interventions in men on ADT were extracted on impairment, functional
      limitation, and physical disability domain outcomes. The average of weighted,
      bias-corrected effect sizes were calculated for each outcome and compared across
      domains. A total of 9 studies (6 randomized controlled trials, 3 uncontrolled
      trials) conducted with 684 PC patients met the inclusion criteria. RESULTS:
      Exercise yielded heterogeneous effect-size improvements in physical impairments,
      ranging from large improvements in muscular strength (d = .74; 95% CI, .14-1.47)
      and endurance (d = 2.64; 95% CI, 1.08-2.84), to small improvements in body
      composition measures (d = .12; 95% CI, -.52-.68). CONCLUSIONS: Whereas exercise
      resulted in meaningful effect-size improvements in functional limitation domain
      outcomes (d = .39; 95% CI, -.42-1.01), fndings from the 4 studies that assessed a
      physical disability, domain outcomes revealed only small improvements (d = .10;
      95% CI, -.44-.43) in these outcomes. Collectively, exercise consistently results
      in meaningful improvements in physical impairments and functional limitations in
      basic physical tasks. However, to date, few studies have evaluated the effects of
      exercise on physical disability domain outcomes, and the results suggest that the
      effects of exercise on physical disability measures are of a smaller magnitude
      relative to those observed for impairment and functional limitation domain
      outcomes.

PMID- 25372365
TI  - Breast cancer in male veteran population: an analysis from VA cancer registry.
AB  - BACKGROUND: Male breast cancer is rare and makes up < 1% of all cases of breast
      cancers. Treatment and survival stage per stage is mainly based on what is known
      from female breast cancer. OBJECTIVES: We determined the pathological features,
      stage, treatment of breast cancer in male veterans and their survival outcome.
      METHODS: Medical records of male patients diagnosed with breast cancer at the
      Veterans Affairs Medical Centers of Washington DC, Baltimore, Maryland, and
      Martinsburg, West Virginia, from 1992-2012 were reviewed after iInstitutional
      review board approval. RESULTS: From 1995-2012, 51 male patients with breast
      cancer were identifed from cancer registry. Of those, 57% were African American,
      41% white, and 2% other race. Median age was 68 years (range, 44-86 years).
      Palpable mass was presenting symptoms in 80%, and gynecomastia or bloody nipple
      discharge in 16%. Family history of breast cancer in immediate family was
      positive in 11 patients without mention of BRCA genes except in one who was BRCA2
      positve. ER/PR (estrogen-/progesterone-receptor) was positive in 71%, ER
      positive/PR-negative in 2%, ER-positive/PR-positive /HER2-positive in 4%, ER
      negative/PR-negative /HER2-triple negative in 4%. In all, 41% and 57% had right
      and left breast cancer, respectively; 80% had mastectomy, 36% had lymph node
      involvement (1-13 LN), 90% had invasive ductal carcinoma, 8% DCIS, and 2%
      sarcoma. Cancer in 26% was stage I, 38% stage II, 18% stage III and 8% stage IV.
      Twenty four percent of the patients had combination chemotherapy, and 66% were
      given tamoxifen. Eight percent had relapsed or recurrent disease within 1-5 years
      of their diagnosis and died within 2-12 years after the relapse. At median follow
      up of 174 months (range, 4 months-19 years), 56% had died, 42% were alive, and 6%
      had been lost to follow-up. LIMITATIONS: This is a very small retrospective chart
      review. Further large prospective studies are desired. CONCLUSIONS: Median age at
      diagnosis of breast cancer seems to be higher in men (70 years) than it is in
      women (60 years). Invasive ductal carcinoma is the main pathology, and 73% of the
      tumors were ER-positive. The survival rate at more than 10 years of follow-up was
      about 40%. Stage versus survival revealed no difference in mortality.

PMID- 25372366
TI  - Acute small bowel obstruction owing to undiagnosed lung cancer.
AB  - Lung cancer is the leading cause of cancer related deaths in the United States.
      Most patients with lung cancer present with advanced disease at the time of
      diagnosis owing to multiple metastases. However, metastases to the duodenum are
      extremely rare. We present a case of acute small bowel obstruction in a patient
      owing to metastatic disease to the duodenum from previously undiagnosed lung
      adenocarcinoma. 

PMID- 25372367
TI  - Moving beyond the one-size-fits-all formula for breast cancer treatments.
AB  - Major advances in the understanding of breast cancer biology have led to new
      treatment options that have dramatically improved the prognosis for breast cancer
      patients in the past few decades. Yet, breast cancer remains a signifcant health
      problem; in 2011 it was estimated that about 2.9 million women were living with
      breast cancer in the United States and median survival in the metastatic setting
      is only 2 years. Thus, the development of new and efective treatment options
      remains a priority. Here, we discuss the most signifcant advances in recent years
      that are changing oncology practice today and for the future. 

PMID- 25372368
TI  - Fast identification of novel lymphoid tyrosine phosphatase inhibitors using
      target-ligand interaction-based virtual screening.
AB  - Lymphoid-specific tyrosine phosphatase (Lyp), a critical signaling regulator of
      immune cells, is associated with various autoimmune diseases, including type 1
      diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Recent research
      suggests that Lyp is a potential drug target for autoimmune diseases. Herein, we
      applied a target-ligand interaction-based virtual screening method to identify
      novel Lyp inhibitors. Nine Lyp inhibitors with novel scaffolds were identified
      with eight reversible inhibitors (Ki values ranged from 2.87 to 28.03 MUM) and
      one covalent inhibitor (Ki = 40.98 +/- 13.19 MUM). The top four compounds (A2,
      A15, A19, and A26) displayed selectivity over other phosphatases in preliminary
      experiments, and kinetic analysis indicated that these compounds are competitive
      inhibitors of Lyp. Compounds A15 and A19 up-regulated TCR (T cell receptor)
      mediated signaling and transcriptional activation through inhibition of Lyp
      activity in T cells. The new chemotypes of Lyp selective inhibitors identified
      through the target-ligand interaction-based virtual screening may provide new
      leads for Lyp targeted therapeutic development. 

PMID- 25372369
TI  - Real-time dual-loop electric current measurement for label-free nanofluidic
      preconcentration chip.
AB  - An electrokinetic trapping (EKT)-based nanofluidic preconcentration device with
      the capability of label-free monitoring trapped biomolecules through real-time
      dual-loop electric current measurement was demonstrated. Universal current
      voltage (I-V) curves of EKT-based preconcentration devices, consisting of two
      microchannels connected by ion-selective channels, are presented for functional
      validation and optimal operation; universal onset current curves indicating the
      appearance of the EKT mechanism serve as a confirmation of the concentrating
      action. The EKT mechanism and the dissimilarity in the current curves related to
      the volume flow rate (Q), diffusion coefficient (D), and diffusion layer (DL)
      thickness were explained by a control volume model with a five-stage
      preconcentration process. Different behaviors of the trapped molecular plug were
      categorized based on four modes associated with different degrees of
      electroosmotic instability (EOI). A label-free approach to preconcentrating
      (bio)molecules and monitoring the multibehavior molecular plug was demonstrated
      through real-time electric current monitoring, rather than through the use of
      microscope images. 

PMID- 25372370
TI  - Single-molecule study on histone-like nucleoid-structuring protein (H-NS)
      paralogue in Pseudomonas aeruginosa: MvaU bears DNA organization mode
      similarities to MvaT.
AB  - Pseudomonas aeruginosa contains two distinct members of H-NS family of nucleoid
      structuring proteins: MvaT and MvaU. Together, these proteins bind to the same
      regions of the chromosome and function coordinately in the regulation of hundreds
      of genes. Due to their structural similarity, they can associate to form
      heteromeric complexes. These findings left us wondering whether they bear similar
      DNA binding properties that underlie their gene-silencing functions. Using single
      molecule stretching and imaging experiments, we found striking similarities in
      the DNA organization modes of MvaU compared to the previously studied MvaT. MvaU
      can form protective nucleoprotein filaments that are insensitive to environmental
      factors, consistent with its role as a repressor of gene expression. Similar to
      MvaT, MvaU filament can mediate DNA bridging while excessive MvaU can cause DNA
      aggregation. The almost identical DNA organization modes of MvaU and MvaT explain
      their functional redundancy, and raise an interesting question regarding the
      evolutionary benefits of having multiple H-NS paralogues in the Pseudomonas
      genus. 

PMID- 25372371
TI  - Endocrinology and pediatric exercise science.

PMID- 25372372
TI  - Exercise in pediatric type 1 diabetes.
AB  - The beneficial effects of exercise, including reduction of cardiovascular risk,
      are especially important in children with type 1 diabetes (T1DM), in whom
      incidence of lifetime cardiovascular complications remains elevated despite good
      glycemic control. Being able to exercise safely is therefore a paramount concern.
      Dysregulated metabolism in T1DM however, causes frequent occurrence of both hypo-
      and hyperglycemia, the former typically associated with prolonged, moderate
      exercise, the latter with higher intensity, if shorter, challenges. While very
      few absolute contraindications to exercising exist in these children, exercise
      should not be started with glycemia outside the 80-250 mg/dl range. Within this
      glycemic range, careful adjustments in insulin administration (reduction or
      infusion rate via insulin pumps, or overall reduction of dosage of multiple
      injections) should be combined with carbohydrate ingestion before/during
      exercise, based on prior, individual experience with specific exercise formats.
      Unfamiliar exercise should always be tackled with exceeding caution, based on
      known responses to other exercise formats. Finally, gaining a deep understanding
      of other complex exercise responses, such as the modulation of inflammatory
      status, which is a major determinant of the cardio-protective effects of
      exercise, can help determine which exercise formats and which individual
      metabolic conditions can lead to maximally beneficial health effects. 

PMID- 25372374
TI  - Adipocytokine and ghrelin responses to acute exercise and sport training in
      children during growth and maturation.
AB  - Physical exercise is known to regulate energy balance. Important to this
      regulatory system is the existence of several peptides that communicate the
      status of body energy stores to the brain and are related to the body fatness
      including leptin, adiponectin and ghrelin. These hormones assist in regulating
      energy balance as well as somatic and pubertal growth in children. It appears
      that rather few studies have investigated the responses of leptin, adiponectin
      and ghrelin to acute exercise and these studies have demonstrated no changes in
      these peptides as a result of exercise. Leptin levels are decreased and may
      remain unchanged advancing from prepuberty to pubertal maturation in young male
      and female athletes. A limited number of studies indicate that adiponectin levels
      are not different between prepubertal and pubertal athletes and untrained
      controls. However, in certain circumstances circulating adiponectin could be
      increased in young athletes after onset of puberty as a result of heavily
      increased energy expenditure. Ghrelin levels are elevated in young sportsmen.
      However, pubertal onset decreases ghrelin levels in boys and girls even in the
      presence of chronically elevated energy expenditure as seen in young athletes.
      Ghrelin may also be used as an indicator of energy imbalance across the menstrual
      cycle in adolescent athletes. There are no studies with high-molecular-weight
      adiponectin and only very few studies with acylated ghrelin responses to acute
      exercise and chronic training have been performed in young athletes. Since these
      forms of adiponectin and ghrelin have been thought to be bioactive forms, further
      studies with these specific forms of adiponectin and ghrelin are needed. In
      conclusion, further studies should be conducted to investigate the response of
      these hormones to acute and chronic negative energy balance to better understand
      their role in regulating energy balance during growth and maturation in young
      athletes. 

PMID- 25372375
TI  - Endocrine response to resistance training in children.

PMID- 25372376
TI  - Can anabolic steroids or human growth hormone affect the growth and maturation of
      adolescent athletes?

PMID- 25372373
TI  - Exercise, hormones and skeletal adaptations during childhood and adolescence.
AB  - Although primarily considered a disorder of the elderly, emerging evidence
      suggests the antecedents of osteoporosis are established during childhood and
      adolescence. A complex interplay of genetic, environmental, hormonal and
      behavioral factors determines skeletal development, and a greater effort is
      needed to identify the most critical factors that establish peak bone strength.
      Indeed, knowledge of modifiable factors that determine skeletal development may
      permit optimization of skeletal health during growth and could potentially offset
      reductions in bone strength with aging. The peripubertal years represent a unique
      period when the skeleton is particularly responsive to loading exercises, and
      there is now overwhelming evidence that exercise can optimize skeletal
      development. While this is not controversial, the most effective exercise
      prescription and how much investment in this prescription is needed to
      significantly impact bone health continues to be debated. Despite considerable
      progress, these issues are not easy to address, and important questions remain
      unresolved. This review focuses on the key determinants of skeletal development,
      whether exercise during childhood and adolescence should be advocated as a safe
      and effective strategy for optimizing peak bone strength, and whether investment
      in exercise early in life protects against the development of osteoporosis and
      fractures later in life. 

PMID- 25372377
TI  - The GH-IGF-I response to typical field sports practices in adolescent athletes: a
      summary.
AB  - The present study compares previous reports on the effect of "real-life" typical
      field individual (i.e., cross-country running and wrestling--representing combat
      versus noncombat sports) and team sports (i.e., volleyball and water polo
      representing water and land team sports) training on GH and IGF-1, the main
      growth factors of the GH->IGF axis, in male and female late pubertal athletes.
      Cross-country running practice and volleyball practice in both males and females
      were associated with significant increases of circulating GH levels, while none
      of the practices led to a significant increase in IGF-I levels. The magnitude
      (percent change) of the GH response to the different practices was determined
      mainly by preexercise GH levels. There was no difference in the training
      associated GH response between individual and team sports practices. The GH
      response to the different typical practices was not influenced by the practice
      associated lactate change. Further studies are needed to better understand the
      effect of real-life typical training in prepubertal and adolescent athletes and
      their role in exercise adaptations.

PMID- 25372379
TI  - Hormonal and metabolic responses to a resistance exercise protocol in lean
      children, obese children and lean adults.
AB  - During childhood, varying exercise modalities are recommended to stimulate normal
      growth, development, and health. This project investigated hormonal and metabolic
      responses triggered by a resistance exercise protocol in lean children (age: 9.3
      +/- 1.4 y, body fat: 18.3 +/- 4.9%), obese children (age: 9.6 +/- 1.3 y, body
      fat: 40.3 +/- 5.2%) and lean adults (age: 23.3 +/- 2.4 y, body fat: 12.7 +/-
      2.9%). The protocol consisted of stepping onto a raised platform (height = 20% of
      stature) while wearing a weighted vest (resistance = 50% of lean body mass).
      Participants completed 6 sets of 10 repetitions per leg with a 1-min rest period
      between sets. Blood samples were obtained at rest preexercise, immediately
      postexercise and 2 times throughout the 1-hr recovery to analyze possible changes
      in hormones and metabolites. Children-adult differences included a larger
      exercise-induced norepinephrine increase in adults vs. children and a decrease in
      glucagon in children but not adults. Similarities between adults and children
      were observed for GH-IGF-1 axis responses. Metabolically, children presented with
      lower glycolytic and increased fat metabolism after exercise than adults did.
      Obesity in childhood negatively influenced GH, insulin, and glucose
      concentrations. While adults occasionally differed from children, amount of
      activated lean mass, not maturation, likely drove these dissimilarities. 

PMID- 25372380
TI  - Initial screening of children treated with second-generation antipsychotics
      points to an association between physical activity and insulin resistance.
AB  - Second-generation antipsychotic (SGA) medications, used to treat youth for a wide
      range of mental health conditions, are associated with excessive weight gain and
      other comorbidities, placing these individuals at high risk for cardiovascular
      disease. Little is known about the effect of physical activity (PA) on
      cardiovascular risk in these children. Anthropometrics, fasting blood sample and
      self-report PA were obtained in 386 children diagnosed with mental health
      conditions (6-18 y). PA was classified as below (<60 min/day) or meets (>=60
      min/day) current recommended guidelines for daily PA in children. SGA-treated (n
      = 166) and SGA-naive (n = 220) were compared in the analysis. The SGA-treated
      children had higher (p < .05) BMI z-score, waist-to-height ratio, fasting
      glucose, and LDL-cholesterol than SGA-naive children. Waist circumference, waist
      to-height ratio, HDL cholesterol, fasting insulin, and HOMA-IR were significantly
      different by PA status. After adjusting for SGA-treatment duration, sex, age, and
      ethnicity, higher PA was associated with lower insulin resistance (HOMA-IR) in
      SGA-treated (mean, 95% CI; below vs. meets: 2.10 [1.84, 2.37] vs. 1.59 [1.37,
      1.81], p = .046) but not in SGA-naive (1.70 [1.47, 1.94] vs. 1.55 [1.35, 1.75], p
      = .707) children. Upon initial screening, SGA-treated children that reported
      meeting the minimal recommendations for daily PA displayed lower measures of
      adiposity and improved insulin resistance.

PMID- 25372381
TI  - Effect of aerobic exercise on hunger feelings and satiety regulating hormones in
      obese teenage girls.
AB  - Exercise is implicated in modifying subsequent energy intake (EI) through
      alterations in hunger and/or satiety hormones. Our aim was to examine the effects
      of aerobic exercise on hunger, satiety regulatory peptides, and EI in obese
      adolescents. Nine obese girls (age: 13-18 years old, BMI: 33.74 +/- 4.04 kg/m2)
      participated in this randomized controlled crossover study. Each participant
      randomly underwent 2 experimental protocols: control (seated for 150 min) and
      exercise (exercised for 30 min on a treadmill performed at ventilatory threshold
      [VT] intensity and then remained seated for 120 min). Leptin, peptide YY(3-36)
      (PYY(3-36)), and subjective hunger were measured at baseline as well as 30 min
      and 150 min, followed by 24-hr EI measurement. Exercise session resulted in an
      acute increase in PYY(3-36) (p < .01) without changes in leptin and/or hunger
      scores. The control session increased hunger scores (p < .01) and decreased
      circulating leptin levels (p = .03). There was a strong effect size for
      carbohydrate intake (d = 2.14) and a modest effect size for protein intake (d =
      0.61) after the exercise compared with the control session. Exercise performed at
      VT intensity in this study appears to provoke a state of transient anorexia in
      obese girls. These changes may be linked to an increase in circulating PYY3-36
      and maintenance of leptin levels.

PMID- 25372382
TI  - IGF-I and IGF-I receptor polymorphisms among elite swimmers.
AB  - In recent years several genetic polymorphisms related to the GH-IGF-I axis were
      suggested to promote athletic excellence in endurance and power sports. We
      studied the presence of the C-1245T SNP (rs35767), a nucleotide substitution in
      the promoter region of the IGF-I gene, and the presence of the 275124A > C SNP
      (rs1464430), a common nucleotide substitution in the intron region of the IGF-I
      receptor (IGF-IR) gene in elite long and short-distance swimmers compared with
      nonphysically active controls. The rare T/T IGF-I polymorphism was found only in
      5.3% of the long-distance swimmers, and was not found at all in the short
      distance swimmers or among the control group participants. The prevalence of the
      IGF-I receptor AA genotype was significantly lower in the swimming group as a
      whole (35%) compared with the control group (46%), in particularly due to reduced
      frequency of the AA genotype among short-distance swimmers (26%). In contrast to
      previous reports in elite endurance and power track and field athletes, single
      nucleotide polymorphisms of the IGF-I and the IGF-IR were not frequent among
      elite Israeli short- and long-distance swimmers emphasizing the importance of
      other factors for excellence in swimming. The results also suggest that despite
      seemingly similar metabolic characteristics different sports disciplines may have
      different genetic polymorphisms. Thus, combining different disciplines for sports
      genetic research purposes should be done with extreme caution. 

PMID- 25372383
TI  - Adipocytokine and ghrelin levels in relation to body composition in rhythmic
      gymnasts entering into puberty: a 3-year follow-up study.
AB  - The aim of this study was to describe longitudinal changes in body composition,
      leptin, adiponectin, and ghrelin over a 36-month period in prepubertal rhythmic
      gymnasts (RG) and their age-matched untrained controls (UC) entering into
      puberty. Thirty-five RG (8.0 +/- 0.6 yrs) and 33 UC (8.2 +/- 0.6 yrs) were
      followed at 12-month intervals for the next 3 years. Height, weight, pubertal
      stage, body composition, leptin, adiponectin, and ghrelin were measured at each
      time points. The pubertal development over the next 36 months was slower in the
      RG compared with UC. Leptin was increased in UC and remained unchanged in RG over
      3-year study period (3.7 +/- 3.6 vs. 0.2 +/- 1.1 ng/ml; p < .05). In RG, baseline
      leptin was negatively correlated with the change in body fat percentage over a 36
      month period (r = -0.34; p < .05). The change in adiponectin over the study
      period was negatively correlated with the change in BMI (r = -0.43; p < .05). RG
      had relative leptin deficiency per body fat mass. In conclusion, relatively high
      leptin concentration at the beginning of puberty may predict those girls who do
      not increase their body fat percentage through coming years and therefore may
      have increased risk for delayed puberty. 

PMID- 25372384
TI  - The MluI cell cycle box (MCB) motifs, but not damage-responsive elements (DREs),
      are responsible for the transcriptional induction of the rhp51+ gene in response
      to DNA replication stress.
AB  - DNA replication stress induces the transcriptional activation of rhp51+, a
      fission yeast recA homolog required for repair of DNA double strand breaks.
      However, the mechanism by which DNA replication stress activates rhp51+
      transcription is not understood. The promoter region of rhp51+ contains two
      damage-responsive elements (DREs) and two MluI cell cycle box (MCB) motifs. Using
      luciferase reporter assays, we examined the role of these elements in rhp51+
      transcription. The full-length rhp51+ promoter and a promoter fragment containing
      MCB motifs only, but not a fragment containing DREs, mediated transcriptional
      activation upon DNA replication stress. Removal of the MCB motifs from the rhp51+
      promoter abolished the induction of rhp51+ transcription by DNA replication
      stress. Consistent with a role for MCB motifs in rhp51+ transcription activation,
      deletion of the MBF (MCB-binding factor) co-repressors Nrm1 and Yox1 precluded
      rhp51+ transcriptional induction in response to DNA replication stress. Using
      cells deficient in checkpoint signaling molecules, we found that the Rad3
      Cds1/Chk1 pathway partially mediated rhp51+ transcription in response to DNA
      replication stress, suggesting the involvement of unidentified checkpoint
      signaling pathways. Because MBF is critical for G1/S transcription, we examined
      how the cell cycle affected rhp51+ transcription. The transcription of rhp51+ and
      cdc18+, an MBF-dependent G1/S gene, peaked simultaneously in synchronized cdc25
      22 cells. Furthermore, DNA replication stress maintained transcription of rhp51+
      similarly to cdc18+. Collectively, these results suggest that MBF and its
      regulators mediate rhp51+ transcription in response to DNA replication stress,
      and underlie rhp51+ transcription at the G1/S transition. 

PMID- 25372385
TI  - A modified recombineering protocol for the genetic manipulation of gene clusters
      in Aspergillus fumigatus.
AB  - Genomic analyses of fungal genome structure have revealed the presence of
      physically-linked groups of genes, termed gene clusters, where collective
      functionality of encoded gene products serves a common biosynthetic purpose. In
      multiple fungal pathogens of humans and plants gene clusters have been shown to
      encode pathways for biosynthesis of secondary metabolites including metabolites
      required for pathogenicity. In the major mould pathogen of humans Aspergillus
      fumigatus, multiple clusters of co-ordinately upregulated genes were identified
      as having heightened transcript abundances, relative to laboratory cultured
      equivalents, during the early stages of murine infection. The aim of this study
      was to develop and optimise a methodology for manipulation of gene cluster
      architecture, thereby providing the means to assess their relevance to fungal
      pathogenicity. To this end we adapted a recombineering methodology which exploits
      lambda phage-mediated recombination of DNA in bacteria, for the generation of
      gene cluster deletion cassettes. By exploiting a pre-existing bacterial
      artificial chromosome (BAC) library of A. fumigatus genomic clones we were able
      to implement single or multiple intra-cluster gene replacement events at both
      subtelomeric and telomere distal chromosomal locations, in both wild type and
      highly recombinogenic A. fumigatus isolates. We then applied the methodology to
      address the boundaries of a gene cluster producing a nematocidal secondary
      metabolite, pseurotin A, and to address the role of this secondary metabolite in
      insect and mammalian responses to A. fumigatus challenge. 

PMID- 25372386
TI  - A comparison of responses to raised extracellular potassium and endothelium
      derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries.
AB  - The present study examined the hypothesis that potassium ions act as an
      endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in
      small mesenteric arteries displaying myogenic tone. Small mesenteric arteries
      isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg.
      After developing myogenic tone, responses to raising extracellular potassium were
      compared to those obtained with ACh (in the presence of nitric oxide synthase and
      cyclo-oxygenase inhibitors). The effects of barium and oubain, or capsaicin, on
      responses to raised extracellular potassium or ACh were also determined. The
      effects of raised extracellular potassium levels and ACh on membrane potential,
      were measured using sharp microelectrodes in pressurised arteries. Rat small
      mesenteric arteries developed myogenic tone when pressurised. On the background
      of vascular tone set by a physiological stimulus (i.e pressure), ACh fully
      dilated the small arteries in a concentration-dependent manner. This response was
      relatively insensitive to the combination of barium and ouabain, and insensitive
      to capsaicin. Raising extracellular potassium produced a more inconsistent and
      modest vasodilator response in pressurised small mesenteric arteries. Responses
      to raising extracellular potassium were sensitive to capsaicin, and the
      combination of barium and ouabain. ACh caused a substantial hyperpolarisation in
      pressurized arteries, while raising extracellular potassium did not. These data
      indicate that K+ is not the EDHF released in response to ACh in myogenically
      active rat mesenteric small arteries. Since the hyperpolarization produced by ACh
      was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH
      responses under physiological conditions. 

PMID- 25372387
TI  - Elevational distribution and ecology of small mammals on Africa's highest
      mountain.
AB  - Mt Kilimanjaro is Africa's highest mountain, and an icon for a country famous for
      its mammalian fauna. The distribution and abundance of small mammals on the
      mountain are poorly known. Here we document the distribution of shrews and
      rodents along an elevational gradient on the southeastern versant of Kilimanjaro.
      Five sites were sampled with elevational center points of 2000, 2500, 3000, 3500
      and 4000 m, using a systematic methodology of standard traps and pitfall lines,
      to inventory the shrews and rodents of the slope. Sixteen species of mammal were
      recorded, including 6 shrew and 10 rodent species, and the greatest diversity of
      both was found at 3000 m, the elevational midpoint of the transect. No species
      previously unrecorded on Kilimanjaro were observed. Two genera of rodents that
      occur in nearby mountains (Hylomyscus and Beamys) were not recorded. Myosorex
      zinki, the only mammal endemic to Mt. Kilimanjaro, which previously was known by
      only a few specimens collected in the ericaceous or moorland habitat, was found
      in all but one (the lowest) of the sites sampled, and was one of the most
      widespread species of small mammal along the gradient. Two shrews (Crocidura
      allex and Sylvisorex granti) and one rodent (Dendromus insignis) were found
      throughout the entire transect, with Dendromus being observed at our highest trap
      point (4240 m). As in similar faunal surveys on other mountains of Tanzania,
      rainfall influenced the sample success of shrews, but not rodents. Trap success
      for rodents at 3500 m was notably low. This study contributes further
      justification for the conservation of the forest habitat of Mt. Kilimanjaro. 

PMID- 25372389
TI  - SlideToolkit: an assistive toolset for the histological quantification of whole
      slide images.
AB  - The demand for accurate and reproducible phenotyping of a disease trait increases
      with the rising number of biobanks and genome wide association studies. Detailed
      analysis of histology is a powerful way of phenotyping human tissues.
      Nonetheless, purely visual assessment of histological slides is time-consuming
      and liable to sampling variation and optical illusions and thereby observer
      variation, and external validation may be cumbersome. Therefore, within our own
      biobank, computerized quantification of digitized histological slides is often
      preferred as a more precise and reproducible, and sometimes more sensitive
      approach. Relatively few free toolkits are, however, available for fully
      digitized microscopic slides, usually known as whole slides images. In order to
      comply with this need, we developed the slideToolkit as a fast method to handle
      large quantities of low contrast whole slides images using advanced cell
      detecting algorithms. The slideToolkit has been developed for modern personal
      computers and high-performance clusters (HPCs) and is available as an open-source
      project on github.com. We here illustrate the power of slideToolkit by a repeated
      measurement of 303 digital slides containing CD3 stained (DAB) abdominal aortic
      aneurysm tissue from a tissue biobank. Our workflow consists of four consecutive
      steps. In the first step (acquisition), whole slide images are collected and
      converted to TIFF files. In the second step (preparation), files are organized.
      The third step (tiles), creates multiple manageable tiles to count. In the fourth
      step (analysis), tissue is analyzed and results are stored in a data set. Using
      this method, two consecutive measurements of 303 slides showed an intraclass
      correlation of 0.99. In conclusion, slideToolkit provides a free, powerful and
      versatile collection of tools for automated feature analysis of whole slide
      images to create reproducible and meaningful phenotypic data sets. 

PMID- 25372388
TI  - Caspase-3 mediates the pathogenic effect of Yersinia pestis YopM in liver of
      C57BL/6 mice and contributes to YopM's function in spleen.
AB  - The virulence protein YopM of the plague bacterium Yersinia pestis has different
      dominant effects in liver and spleen. Previous studies focused on spleen, where
      YopM inhibits accumulation of inflammatory dendritic cells. In the present study
      we focused on liver, where PMN function may be directly undermined by YopM
      without changes in inflammatory cell numbers in the initial days of infection,
      and foci of inflammation are easily identified. Mice were infected with parent
      and DeltayopM-1 Y. pestis KIM5, and effects of YopM were assessed by
      immunohistochemistry and determinations of bacterial viable numbers in organs.
      The bacteria were found associated with myeloid cells in foci of inflammation and
      in liver sinusoids. A new in-vivo phenotype of YopM was revealed: death of
      inflammatory cells, evidenced by TUNEL staining beginning at d 1 of infection.
      Based on distributions of Ly6G(+), F4/80(+), and iNOS(+) cells within foci, the
      cells that were killed could have included both PMNs and macrophages. By 2 d post
      infection, YopM had no effect on distribution of these cells, but by 3 d cellular
      decomposition had outstripped acute inflammation in foci due to parent Y. pestis,
      while foci due to the DeltayopM-1 strain still contained many inflammatory cells.
      The destruction depended on the presence of both PMNs in the mice and YopM in the
      bacteria. In mice that lacked the apoptosis mediator caspase-3 the infection
      dynamics were novel: the parent Y. pestis was limited in growth comparably to the
      DeltayopM-1 strain in liver, and in spleen a partial growth limitation for parent
      Y. pestis was seen. This result identified caspase-3 as a co-factor or effector
      in YopM's action and supports the hypothesis that in liver YopM's main pathogenic
      effect is mediated by caspase-3 to cause apoptosis of PMNs.

PMID- 25372390
TI  - Intestinal microbiota is different in women with preterm birth: results from
      terminal restriction fragment length polymorphism analysis.
AB  - Preterm birth is a leading cause of perinatal morbidity and mortality. Studies
      using a cultivation method or molecular identification have shown that bacterial
      vaginosis is one of the risk factors for preterm birth. However, an association
      between preterm birth and intestinal microbiota has not been reported using
      molecular techniques, although the vaginal microbiota changes during pregnancy.
      Our aim here was to clarify the difference in intestinal and vaginal microbiota
      between women with preterm birth and women without preterm labor. 16S ribosomal
      ribonucleic acid genes were amplified from fecal and vaginal DNA by polymerase
      chain reaction. Using terminal restriction fragment length polymorphism (T-RFLP),
      we compared the levels of operational taxonomic units of both intestinal and
      vaginal flora among three groups: pregnant women who delivered term babies
      without preterm labor (non-PTL group) (n = 20), those who had preterm labor but
      delivered term babies (PTL group) (n = 11), and those who had preterm birth (PTB
      group) (n = 10). Significantly low levels of Clostridium subcluster XVIII,
      Clostridium cluster IV, Clostridium subcluster XIVa, and Bacteroides, and a
      significantly high level of Lactobacillales were observed in the intestinal
      microbiota in the PTB group compared with those in the non-PTL group. The levels
      of Clostridium subcluster XVIII and Clostridium subcluster XIVa in the PTB group
      were significantly lower than those in the PTL group, and these levels in the PTL
      group were significantly lower than those in non-PTL group. However, there were
      no significant differences in vaginal microbiota among the three groups.
      Intestinal microbiota in the PTB group was found to differ from that in the non
      PTL group using the T-RFLP method.

PMID- 25372391
TI  - HIV treatment adherence measurement and reporting concordance in youth with
      perinatally acquired HIV infection and their caregivers.
AB  - We examined youth-caregiver adherence report concordance and association of
      different adherence self-report items with HIV RNA viral load (VL) in perinatally
      HIV-infected adolescents assessed in 2003-2008. Youth (n=194; 9-19 years) and
      their caregivers completed a multi-step 2-day recall, one item on last time
      medications were missed, and one item on responsibility for managing youths'
      medications. Across early (9-12 years), middle (13-15 years), and late (16+years)
      adolescence, both youth and caregivers reported having primary responsibility for
      youths' medication regimens and demonstrated poor to moderate youth-caregiver
      concordance on adherence items. Responses to the last-time-missed item had
      greater association with VL than did the 2-day recall, particularly for longer
      times (e.g., past month). By age group, significant associations with VL were
      found for caregiver reports in early adolescence, caregiver and youth reports in
      middle adolescence, and youth reports in late adolescence, suggesting that
      caregivers offer better reports of youth adherence during early adolescence, but
      by later adolescence, youth are better informants. Although design limitations
      preclude definitive conclusions about the reliability and validity of specific
      adherence items, this study suggests important issues related to age group,
      caregiver vs. youth informants of adherence, and recall periods for child
      adherence assessment that warrant further research.

PMID- 25372394
TI  - Antibacterial and antioxidant activity of essential oil terpenes against
      pathogenic and spoilage-forming bacteria and cell structure-activity
      relationships evaluated by SEM microscopy.
AB  - The antibacterial activity and antioxidant effect of the compounds alpha
      terpineol, linalool, eucalyptol and alpha-pinene obtained from essential oils
      (EOs), against pathogenic and spoilage forming bacteria were determined. The
      antibacterial activities of these compounds were observed in vitro on four Gram
      negative and three Gram-positive strains. S. putrefaciens was the most resistant
      bacteria to all tested components, with MIC values of 2% or higher, whereas E.
      coli O157:H7 was the most sensitive strain among the tested bacteria. Eucalyptol
      extended the lag phase of S. Typhimurium, E. coli O157:H7 and S. aureus at the
      concentrations of 0.7%, 0.6% and 1%, respectively. In vitro cell growth
      experiments showed the tested compounds had toxic effects on all bacterial
      species with different level of potency. Synergistic and additive effects were
      observed at least one dose pair of combination against S. Typhimurium, E. coli
      O157:H7 and S. aureus, however antagonistic effects were not found in these
      combinations. The results of this first study are encouraging for further
      investigations on mechanisms of antimicrobial activity of these EO components. 

PMID- 25372392
TI  - Potentially functional SNPs (pfSNPs) as novel genomic predictors of 5-FU response
      in metastatic colorectal cancer patients.
AB  - 5-Fluorouracil (5-FU) and its pro-drug Capecitabine have been widely used in
      treating colorectal cancer. However, not all patients will respond to the drug,
      hence there is a need to develop reliable early predictive biomarkers for 5-FU
      response. Here, we report a novel potentially functional Single Nucleotide
      Polymorphism (pfSNP) approach to identify SNPs that may serve as predictive
      biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC)
      patients. 1547 pfSNPs and one variable number tandem repeat (VNTR) in 139 genes
      in 5-FU drug (both PK and PD pathway) and colorectal cancer disease pathways were
      examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by
      RECIST criteria was used as the clinical end point. Four non-responder-specific
      pfSNPs were found to account for 37.5% of all non-responders (P<0.0003). Five
      additional pfSNPs were identified from a multivariate model (AUC under ROC =
      0.875) that was applied for all other pfSNPs, excluding the non-responder
      specific pfSNPs. These pfSNPs, which can differentiate the other non-responders
      from responders, mainly reside in tumor suppressor genes or genes implicated in
      colorectal cancer risk. Hence, a total of 9 novel SNPs with potential functional
      significance may be able to distinguish non-responders from responders to 5-FU.
      These pfSNPs may be useful biomarkers for predicting response to 5-FU. 

PMID- 25372395
TI  - Identification of a new peritrophic membrane protein from larval Holotrichia
      parallela (Coleoptera: Motschulsky).
AB  - Peritrophic membranes (PMs) are composed of proteins, proteoglycans and chitin
      that play important roles in the structural formation and function of the PM.
      This study identified and characterized a new chitin binding protein named
      HpCBP45 by immunoscreening of the Holotrichia parallela larvae midgut expression
      library. The predicted amino acid sequence indicates that it contains eight
      tandem chitin binding domains belonging to the peritrophin-A family. The HpCBP45
      protein was expressed as a recombinant protein in the yeast Pichia pastoris and
      chitin binding assay demonstrated that recombinant HpCBP45 protein could strongly
      bind to chitin. qRT-PCR analysis showed that HpCBP45 was mainly localized in the
      midgut, further confirming the H. parallela PM belongs to Type I PM. The
      discovery and characterization of the peritrophic membrane protein HpCBP45
      provides a basis for the further investigation of its biochemical and
      physiological functions in H. parallela. 

PMID- 25372396
TI  - Support for a photoprotective function of winter leaf reddening in nitrogen
      deficient individuals of Lonicera japonica.
AB  - Plants growing in high-light environments during winter often exhibit leaf
      reddening due to synthesis of anthocyanin pigments, which are thought to
      alleviate photooxidative stress associated with low-temperature photoinhibition
      through light attenuation and/or antioxidant activity. Seasonal high-light stress
      can be further exacerbated by a limited photosynthetic capacity, such as nitrogen
      deficiency. In the present study, we test the following hypotheses using three
      populations of the semi-evergreen vine Lonicera japonica: (1) nitrogen deficiency
      corresponds with reduced photosynthetic capacity; (2) individuals with reduced
      photosynthetic capacity synthesize anthocyanin pigments in leaves during winter;
      and (3) anthocyanin pigments help alleviate high-light stress by attenuating
      green light. All populations featured co-occurring winter-green and winter-red
      leafed individuals on fully-exposed (high-light), south-facing slopes in the
      Piedmont of North Carolina, USA. Consistent with our hypotheses, red leaves
      consistently exhibited significantly lower foliar nitrogen than green leaves, as
      well as lower total chlorophyll, quantum yield efficiency, carboxylation
      efficiency, and photosynthesis at saturating irradiance (Asat). Light-response
      curves measured using ambient sunlight versus red-blue LED (i.e., lacking green
      wavelengths) demonstrated significantly reduced quantum yield efficiency and a
      higher light compensation point under sunlight relative to red-blue LED in red
      leaves, but not in green leaves, consistent with a (green) light-attenuating
      function of anthocyanin pigments. These results are consistent with the
      hypothesis that intraspecific anthocyanin synthesis corresponds with nitrogen
      deficiency and reduced photosynthetic capacity within populations, and support a
      light-attenuating function of anthocyanin pigments. 

PMID- 25372397
TI  - Antioxidant and anticancer aporphine alkaloids from the leaves of Nelumbo
      nucifera Gaertn. cv. Rosa-plena.
AB  - Fifteen compounds were extracted and purified from the leaves of Nelumbo nucifera
      Gaertn. cv. Rosa-plena. These compounds include liriodenine (1), lysicamine (2),
      (-)-anonaine (3), (-)-asimilobine (4), (-)-caaverine (5), (-)-N-methylasimilobine
      (6), (-)-nuciferine (7), (-)-nornuciferine (8), (-)-roemerine (9), 7
      hydroxydehydronuciferine (10) cepharadione B (11), beta-sitostenone (12),
      stigmasta-4,22-dien-3-one (13) and two chlorophylls: pheophytin-a (14) and
      aristophyll-C (15). The anti-oxidation activity of the compounds was examined by
      antiradical scavenging, metal chelating and ferric reducing power assays. The
      results have shown that these compounds have antioxidative activity. The study
      has also examined the antiproliferation activity of the isolated compounds
      against human melanoma, prostate and gastric cancer cells. The results shown that
      7-hydroxydehydronuciferine (10) significantly inhibited the proliferation of
      melanoma, prostate and gastric cancer cells. Together, these findings suggest
      that leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena are a good resource for
      obtaining the biologically active substances with antioxidant properties. 

PMID- 25372398
TI  - A new prenylated indole diketopiperazine alkaloid from Eurotium cristatum.
AB  - A new prenylated indole diketopiperazine alkaloid, cristatumin F (1), and four
      known metabolites, echinulin (2), dehydroechinulin (3), neoechinulin A (4) and
      variecolorin O (5), were isolated from the crude extract of the fungus Eurotium
      cristatum. The structure of 1 was elucidated primarily by NMR and MS methods. The
      absolute configuration of 1 was assigned using Marfey's method applied to its
      acid hydrolyzate. Cristatumin F (1) showed modest radical scavenging activity
      against DPPH radicals, and exhibited marginal attenuation of 3T3L1 pre
      adipocytes. 

PMID- 25372399
TI  - Associations between multiple accelerometry-assessed physical activity parameters
      and selected health outcomes in elderly people--results from the KORA-age study.
AB  - INTRODUCTION: Accelerometry is an important method for extending our knowledge
      about intensity, duration, frequency and patterns of physical activity needed to
      promote health. This study has used accelerometry to detect associations between
      intensity levels and related activity patterns with multimorbidity and
      disability. Moreover, the proportion of people meeting the physical activity
      recommendations for older people was assessed. METHODS: Physical activity was
      measured in 168 subjects (78 males; 65-89 years of age), using triaxial GT3X
      accelerometers for ten consecutive days. The associations between physical
      activity parameters and multimorbidity or disability was examined using multiple
      logistic regression models, which were adjusted for gender, age, education,
      smoking, alcohol consumption, lung function, nutrition and multimorbidity or
      disability. RESULTS: 35.7% of the participants met the physical activity
      recommendations of at least 150 minutes of moderate to vigorous activity per
      week. Only 11.9% reached these 150 minutes, when only bouts of at least 10
      minutes were counted. Differences in moderate to vigorous activity between people
      with and without multimorbidity or disability were more obvious when shorter
      bouts instead of only longer bouts were included. Univariate analyses showed an
      inverse relationship between physical activity and multimorbidity or disability
      for light and moderate to vigorous physical activity. A higher proportion of long
      activity bouts spent sedentarily was associated with higher risk for
      multimorbidity, whereas a high proportion of long bouts in light activity seemed
      to prevent disability. After adjustment for covariates, there were no significant
      associations, anymore. CONCLUSIONS: The accumulated time in moderate to vigorous
      physical activity seems to have a stronger relationship with health and
      functioning when shorter activity bouts and not only longer bouts were counted.
      We could not detect an association of the intensity levels or activity patterns
      with multimorbidity or disability in elderly people after adjustment for
      covariates.

PMID- 25372400
TI  - High-yield harvest of nanofibers/mesoporous carbon composite by pyrolysis of
      waste biomass and its application for high durability electrochemical energy
      storage.
AB  - Disposal and recycling of the large scale biomass waste is of great concern.
      Themochemically converting the waste biomass to functional carbon nanomaterials
      and bio-oil is an environmentally friendly apporach by reducing greenhouse gas
      emissions and air pollution caused by open burning. In this work, we reported a
      scalable, "green" method for the synthesis of the nanofibers/mesoporous carbon
      composites through pyrolysis of the Fe(III)-preloaded biomass, which is
      controllable by adjustment of temperature and additive of catalyst. It is found
      that the coupled catalytic action of both Fe and Cl species is able to
      effectively catalyze the growth of the carbon nanofibers on the mesoporous carbon
      and form magnetic nanofibers/mesoporous carbon composites (M-NMCCs). The
      mechanism for the growth of the nanofibers is proposed as an in situ vapor
      deposition process, and confirmed by the XRD and SEM results. M-NMCCs can be
      directly used as electrode materials for electrochemical energy storage without
      further separation, and exhibit favorable energy storage performance with high
      EDLC capacitance, good retention capability, and excellent stability and
      durability (more than 98% capacitance retention after 10,000 cycles). Considering
      that biomass is a naturally abundant and renewable resource (over billions tons
      biomass produced every year globally) and pyrolysis is a proven technique, M
      NMCCs can be easily produced at large scale and become a sustainable and reliable
      resource for clean energy storage.

PMID- 25372401
TI  - Pharmacological inhibition of the chemokine CXCL16 diminishes liver macrophage
      infiltration and steatohepatitis in chronic hepatic injury.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a major cause of morbidity and
      mortality in developed countries, resulting in steatohepatitis (NASH), fibrosis
      and eventually cirrhosis. Modulating inflammatory mediators such as chemokines
      may represent a novel therapeutic strategy for NAFLD. We recently demonstrated
      that the chemokine receptor CXCR6 promotes hepatic NKT cell accumulation, thereby
      controlling inflammation in experimental NAFLD. In this study, we first
      investigated human biopsies (n = 20), confirming that accumulation of
      inflammatory cells such as macrophages is a hallmark of progressive NAFLD.
      Moreover, CXCR6 gene expression correlated with the inflammatory activity (ALT
      levels) in human NAFLD. We then tested the hypothesis that pharmacological
      inhibition of CXCL16 might hold therapeutic potential in NAFLD, using mouse
      models of acute carbon tetrachloride (CCl4)- and chronic methionine-choline
      deficient (MCD) diet-induced hepatic injury. Neutralizing CXCL16 by i.p.
      injection of anti-CXCL16 antibody inhibited the early intrahepatic NKT cell
      accumulation upon acute toxic injury in vivo. Weekly therapeutic anti-CXCL16
      administrations during the last 3 weeks of 6 weeks MCD diet significantly
      decreased the infiltration of inflammatory macrophages into the liver and
      intrahepatic levels of inflammatory cytokines like TNF or MCP-1. Importantly,
      anti-CXCL16 treatment significantly reduced fatty liver degeneration upon MCD
      diet, as assessed by hepatic triglyceride levels, histological steatosis scoring
      and quantification of lipid droplets. Moreover, injured hepatocytes up-regulated
      CXCL16 expression, indicating that scavenging functions of CXCL16 might be
      additionally involved in the pathogenesis of NAFLD. Targeting CXCL16 might
      therefore represent a promising novel therapeutic approach for liver inflammation
      and steatohepatitis.

PMID- 25372402
TI  - Antimicrobial GL13K peptide coatings killed and ruptured the wall of
      Streptococcus gordonii and prevented formation and growth of biofilms.
AB  - Infection is one of the most prevalent causes for dental implant failure. We have
      developed a novel antimicrobial peptide coating on titanium by immobilizing the
      antimicrobial peptide GL13K. GL13K was developed from the human salivary protein
      BPIFA2. The peptide exhibited MIC of 8 ug/ml against planktonic Pseudonomas
      aeruginosa and their biofilms were reduced by three orders of magnitude with 100
      ug/ml GL13K. This peptide concentration also killed 100% of Streptococcus
      gordonii. At 1 mg/ml, GL13K caused less than 10% lysis of human red blood cells,
      suggesting low toxicity to mammalian cells. Our GL13K coating has also previously
      showed bactericidal effect and inhibition of biofilm growth against peri
      implantitis related pathogens, such as Porphyromonas gingivalis. The GL13K
      coating was cytocompatible with human fibroblasts and osteoblasts. However, the
      bioactivity of antimicrobial coatings has been commonly tested under
      (quasi)static culture conditions that are far from simulating conditions for
      biofilm formation and growth in the oral cavity. Oral salivary flow over a
      coating is persistent, applies continuous shear forces, and supplies sustained
      nutrition to bacteria. This accelerates bacteria metabolism and biofilm growth.
      In this work, the antimicrobial effect of the coating was tested against
      Streptococcus gordonii, a primary colonizer that provides attachment for the
      biofilm accretion by P. gingivalis, using a drip-flow biofilm bioreactor with
      media flow rates simulating salivary flow. The GL13K peptide coatings killed
      bacteria and prevented formation and growth of S. gordonii biofilms in the drip
      flow bioreactor and under regular mild-agitation conditions. Surprisingly the
      interaction of the bacteria with the GL13K peptide coatings ruptured the cell
      wall at their septum or polar areas leaving empty shell-like structures or
      exposed protoplasts. The cell wall rupture was not detected under regular culture
      conditions, suggesting that cell wall rupture induced by GL13K peptides also
      requires media flow and possible attendant biological sequelae of the conditions
      in the bioreactor. 

PMID- 25372403
TI  - Comparison of clinical manifestations and outcomes between hepatitis B virus- and
      hepatitis C virus-related hepatocellular carcinoma: analysis of a nationwide
      cohort.
AB  - BACKGROUND: We analyzed whether difference exist in the clinical manifestations
      and outcomes of hepatocellular carcinoma (HCC) according to the two major
      etiologies of HCC from a nationwide, population-based, random HCC registry.
      METHODS: Of the 31,521 new HCC cases registered at the Korea Central Cancer
      Registry between 2003 and 2005, 4,630 (14.7%) were randomly abstracted, and
      followed up until December 2011. Of those, 2,785 hepatitis B virus (HBV)-related
      and 447 hepatitis C virus (HCV)-related HCC patients were compared. RESULTS: The
      mean annual incidence rates of HBV- and HCV-related HCC incidence per 100,000
      persons were 20.8 and 4.9, respectively. The annual incidence rate of HBV-related
      HCC peaked at 50-59 age group (46.5 per 100,000 persons), while the annual
      incidence rate of HCV-related HCC increased gradually to the >= 70 year age group
      (13.2 per 100,000 persons). Large tumors (>= 5 cm) and portal vein invasion at
      initial diagnosis were more frequent in HBV-related HCC, while multiple tumors
      were more frequent in HCV-related HCC. In outcome analysis, HBV-related HCC
      showed poorer survival than HCV-related HCC [median survival: 1.34 vs. 2.17
      years, adjusted hazard ratio (95% confidence interval): 0.88 (0.78-0.98), P =
      0.03, adjusted for age, gender, Child-Pugh class, AJCC/mUICC stage, and initial
      treatment modality]. However, when divided according to the AJCC/mUICC stage,
      survival difference was observed only for those with AJCC/mUICC stage IV tumor,
      but not for AJCC/mUICC stage I, II or III tumors. The treatment outcome of each
      modality (resection, ablation, and transartherial chemoeombolization) was
      comparable between the two etiologies. CONCLUSION: HBV-related and HCV-related
      HCC have clear differences in clinical manifestation, requiring different
      screening strategy according to etiology to optimize HCC surveillance in HBV
      endemic area. However, etiology did not affect treatment outcomes and long-term
      survival within the same stage except for far advanced tumors.

PMID- 25372404
TI  - Physiological comparison of concentric and eccentric arm cycling in males and
      females.
AB  - Lower body eccentric exercise is well known to elicit high levels of muscular
      force with relatively low cardiovascular and metabolic strain. As a result,
      eccentric exercise has been successfully utilised as an adaptive stressor to
      improve lower body muscle function in populations ranging from the frail and
      debilitated, to highly-trained individuals. Here we investigate the metabolic,
      cardiorespiratory, and energy costs of upper body eccentric exercise in a healthy
      population. Seven men and seven women performed 4-min efforts of eccentric (ECC)
      or concentric (CON) arm cycling on a novel arm ergometer at workloads
      corresponding to 40, 60, and 80% of their peak workload as assessed in an
      incremental concentric trial. The heart rate, ventilation, cardiac output,
      respiratory exchange ratio, and blood lactate concentrations were all clearly
      greater in CON condition at all of the relative workloads (all p<0.003). Effect
      size calculations demonstrated that the magnitude of the differences in VO2 and
      work economy between the ECC and CON exercise ranged from very large to extremely
      large; however, in no case did mechanical efficiency (eta(MECH)) differ between
      the conditions (all p>0.05). In contrast, delta efficiency (etaDelta), as
      previously defined by Coyle and colleagues in 1992, demonstrated a sex difference
      (men>women; p<0.05). Sex differences were also apparent in arteriovenous oxygen
      difference and heart rate during CON. Here, we reinforce the high-force, low cost
      attributes of eccentric exercise which can be generalised to the muscles of the
      upper body. Upper body eccentric exercise is likely to form a useful adjunct in
      debilitative, rehabilitative, and adaptive clinical exercise programs; however,
      reports of a shift towards an oxidative phenotype should be taken into
      consideration by power athletes. We suggest delta efficiency as a sensitive
      measure of efficiency that allowed the identification of sex differences.

PMID- 25372405
TI  - The neural code for auditory space depends on sound frequency and head size in an
      optimal manner.
AB  - A major cue to the location of a sound source is the interaural time difference
      (ITD)-the difference in sound arrival time at the two ears. The neural
      representation of this auditory cue is unresolved. The classic model of ITD
      coding, dominant for a half-century, posits that the distribution of best ITDs
      (the ITD evoking a neuron's maximal response) is unimodal and largely within the
      range of ITDs permitted by head-size. This is often interpreted as a place code
      for source location. An alternative model, based on neurophysiology in small
      mammals, posits a bimodal distribution of best ITDs with exquisite sensitivity to
      ITDs generated by means of relative firing rates between the distributions.
      Recently, an optimal-coding model was proposed, unifying the disparate features
      of these two models under the framework of efficient coding by neural
      populations. The optimal-coding model predicts that distributions of best ITDs
      depend on head size and sound frequency: for high frequencies and large heads it
      resembles the classic model, for low frequencies and small head sizes it
      resembles the bimodal model. The optimal-coding model makes key, yet unobserved,
      predictions: for many species, including humans, both forms of neural
      representation are employed, depending on sound frequency. Furthermore, novel
      representations are predicted for intermediate frequencies. Here, we examine
      these predictions in neurophysiological data from five mammalian species:
      macaque, guinea pig, cat, gerbil and kangaroo rat. We present the first evidence
      supporting these untested predictions, and demonstrate that different
      representations appear to be employed at different sound frequencies in the same
      species. 

PMID- 25372406
TI  - Cropping systems and cultural practices determine the Rhizoctonia anastomosis
      groups associated with Brassica spp. in Vietnam.
AB  - Ninety seven Rhizoctonia isolates were collected from different Brassica species
      with typical Rhizoctonia symptoms in different provinces of Vietnam. The isolates
      were identified using staining of nuclei and sequencing of the rDNA-ITS barcoding
      gene. The majority of the isolates were multinucleate R. solani and four isolates
      were binucleate Rhizoctonia belonging to anastomosis groups (AGs) AG-A and a new
      subgroup of A-F that we introduce here as AG-Fc on the basis of differences in
      rDNA-ITS sequence. The most prevalent multinucleate AG was AG 1-IA (45.4% of
      isolates), followed by AG 1-ID (17.5%), AG 1-IB (13.4%), AG 4-HGI (12.4%), AG 2-2
      (5.2%), AG 7 (1.0%) and an unknown AG related to AG 1-IA and AG 1-IE that we
      introduce here as AG 1-IG (1.0%) on the basis of differences in rDNA-ITS
      sequence. AG 1-IA and AG 1-ID have not been reported before on Brassica spp.
      Pathogenicity tests revealed that isolates from all AGs, except AG-A, induced
      symptoms on detached leaves of several cabbage species. In in vitro tests on
      white cabbage and Chinese cabbage, both hosts were severely infected by AG 1-IB,
      AG 2-2, AG 4-HGI, AG 1-IG and AG-Fc isolates, while under greenhouse conditions,
      only AG 4-HGI, AG 2-2 and AG-Fc isolates could cause severe disease symptoms. The
      occurrence of the different AGs seems to be correlated with the cropping systems
      and cultural practices in different sampling areas suggesting that agricultural
      practices determine the AGs associated with Brassica plants in Vietnam. 

PMID- 25372408
TI  - Soluble non-cross-linked poly(norbornene) supports for peptide synthesis with
      minimal reagents.
AB  - Solid-phase peptide synthesis has been an attractive method for synthesizing
      peptides because it is quick and can be automated. The heterogeneous reaction
      medium in solid-phase peptide synthesis necessitates the use of large equivalents
      of reagents to drive the reactions to completion. Peptide synthesis using
      soluble, yet isolable, supports is an attractive alternative to solid-phase
      peptide synthesis. Reported herein is a soluble poly(norbornene)-derived support
      containing multiple attachment sites for high loading capacities and solubilizing
      oligoether/alkyl groups. The Ala-attached support has been used to synthesize tri
      to octapeptides in 28 to 97% yields using only 1.2 equiv of amino acids and
      coupling reagents. The acyclic hexapeptide precursor to natural product segatalin
      A was synthesized in 41% yield on the support using one-eighth of the equivalents
      of coupling reagents compared to that in reported procedures. The support could
      be recovered in up to 98% yield after peptide synthesis, and the recovered
      support was utilized to synthesize tri- and tetrapeptides that contain amino
      acids other than Ala at the C-terminus in ca. 80% yields. 

PMID- 25372407
TI  - Artificial corneas versus donor corneas for repeat corneal transplants.
AB  - BACKGROUND: Individuals who have failed one or more full thickness penetrating
      keratoplasties (PKs) may be offered repeat corneal surgery using an artificial or
      donor cornea. An artificial or prosthetic cornea is known as a keratoprosthesis.
      Both donor and artificial corneal transplantations involve removal of the
      diseased and opaque recipient cornea (or the previously failed cornea) and
      replacement with another donor or prosthetic cornea. OBJECTIVES: To assess the
      effectiveness of artificial versus donor corneas in individuals who have had one
      or more failed donor corneal transplantations. SEARCH METHODS: We searched
      CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register)
      (2013, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed
      Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013),
      EMBASE (January 1980 to November 2013), Latin American and Caribbean Health
      Sciences Literature Database (LILACS) (January 1982 to November 2013), 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 27 November 2013. SELECTION CRITERIA: Two review authors independently
      assessed reports from the electronic searches to identify randomized controlled
      trials (RCTs) or controlled clinical trials (CCTs). We resolved discrepancies by
      discussion or consultation with a third review author. DATA COLLECTION AND
      ANALYSIS: For discussion purposes, we assessed findings from observational cohort
      studies and non-comparative case series. No data synthesis was performed. MAIN
      RESULTS: We did not identify any RCTs or CCTs comparing artificial corneas with
      donor corneas for repeat corneal transplantations. AUTHORS' CONCLUSIONS: The
      optimal management for those individuals who have failed a conventional corneal
      transplantation is not known. Currently, in some centers, artificial corneal
      devices routinely are recommended after just one graft failure, and in others,
      not until after multiple graft failures, or not at all. To date, there have been
      no controlled trials comparing the visual outcomes and complications of
      artificial corneal devices (particularly the Boston type 1 keratoprosthesis which
      is the most commonly implanted artificial corneal device) with repeat donor
      corneal transplantation, in order to guide surgeons and their patients. It is
      apparent that such a trial is needed and would offer significant benefit to an
      ever-increasing pool of people with visual disability due to corneal
      opacification, most of whom are still in productive stages of their lives.

PMID- 25372409
TI  - Electrophilicity of pyridazine-3-carbonitrile, pyrimidine-2-carbonitrile, and
      pyridine-carbonitrile derivatives: a chemical model to describe the formation of
      thiazoline derivatives in human liver microsomes.
AB  - Certain aromatic nitriles are well-known inhibitors of cysteine proteases. The
      mode of action of these compounds involves the formation of a reversible or
      irreversible covalent bond between the nitrile and a thiol group in the active
      site of the enzyme. However, the reactivity of these aromatic nitrile-substituted
      heterocycles may lead inadvertently to nonspecific interactions with DNA,
      protein, glutathione, and other endogenous components, resulting in toxicity and
      complicating the use of these compounds as therapeutic agents. In the present
      study, the intrinsic reactivity and associated structure-property relationships
      of cathepsin K inhibitors featuring substituted pyridazines [6-phenylpyridazine-3
      carbonitrile, 6-(4-fluorophenyl)pyridazine-3-carbonitrile, 6-(4
      methoxyphenyl)pyridazine-3-carbonitrile, 6-p-tolylpyridazine-3-carbonitrile],
      pyrimidines [5-p-tolylpyrimidine-2-carbonitrile, 5-(4-fluorophenyl)pyrimidine-2
      carbonitrile], and pyridines [5-p-tolylpicolinonitrile and 5-(4
      fluorophenyl)picolinonitrile] were evaluated using a combination of computational
      and analytical approaches to establish correlations between electrophilicity and
      levels of metabolites that were formed in glutathione- and N-acetylcysteine
      supplemented human liver microsomes. Metabolites that were characterized in this
      study featured substituted thiazolines that were formed following rearrangements
      of transient glutathione and N-acetylcysteine conjugates. Peptidases including
      gamma-glutamyltranspeptidase were shown to catalyze the formation of these
      products, which were formed to lesser extents in the presence of the selective
      gamma-glutamyltranspeptidase inhibitor acivicin and the nonspecific peptidase
      inhibitors phenylmethylsulfonyl fluoride and aprotinin. Of the chemical series
      mentioned above, the pyrimidine series was the most susceptible to metabolism to
      thiazoline-containing products, followed, in order, by the pyridazine and
      pyridine series. This trend was in keeping with the diminishing electrophilicity
      across these series, as demonstrated by in silico modeling. Hence, mechanistic
      insights gained from this study could be used to assist a medicinal chemistry
      campaign to design cysteine protease inhibitors that were less prone to the
      formation of covalent adducts.

PMID- 25372410
TI  - A near ambient pressure XPS study of subnanometer silver clusters on Al2O3 and
      TiO2 ultrathin film supports.
AB  - We have investigated model systems of silver clusters with different sizes (3 and
      15 atoms) deposited on alumina and titania supports using ambient pressure X-ray
      photoelectron spectroscopy. The electronic structures of silver clusters and
      support materials are studied upon exposure to various atmospheres (ultrahigh
      vacuum, O2 and CO) at different temperatures. Compared to bulk silver, the
      binding energies of silver clusters are about 0.55 eV higher on TiO2 and 0.95 eV
      higher on Al2O3 due to the final state effect and the interaction with supports.
      No clear size effect of the silver XPS peak is observed on different silver
      clusters among these samples. Silver clusters on titania show better stability
      against sintering. Al 2p and Ti 2p core level peak positions of the alumina and
      titania support surfaces change upon exposure to oxygen while the Ag 3d core
      level position remains unchanged. We discuss the origin of these core level
      shifts and their implications for catalytic properties of Ag clusters. 

PMID- 25372411
TI  - Origin of Fermi-level pinning at GaAs surfaces and interfaces.
AB  - Through first-principles simulation methods, we assign the origin of Fermi-level
      pinning at GaAs surfaces and interfaces to the bistability between the As-As
      dimer and two As dangling bonds, which transform into each other upon charge
      trapping. This defect is shown to be naturally formed both at GaAs surfaces upon
      oxygen deposition and in the near-interface substoichiometric oxide. Using
      electron-counting arguments, we infer that the identified defect occurs in
      opposite charge states. The Fermi-level pinning then results from the amphoteric
      nature of this defect which drives the Fermi level to its defect level. These
      results account for the experimental characterization at both GaAs surfaces and
      interfaces within a unified picture, wherein the role of As antisites is
      elucidated. 

PMID- 25372412
TI  - Broad scope hydrofunctionalization of styrene derivatives using iron-catalyzed
      hydromagnesiation.
AB  - The highly regioselective iron-catalyzed formal hydrofunctionalization of styrene
      derivatives with a diverse range of electrophiles has been developed using a
      single, operationally simple hydromagnesiation procedure and only commercially
      available, bench-stable reagents. Using just 0.5 mol % FeCl2.4H2O and N,N,N',N'
      tetramethylethylenediamine, hydromagnesiation and electrophilic trapping have
      been used to form new carbon-carbon bonds (13 examples) and carbon-heteroatom
      bonds (5 examples) including the products of formal cross-coupling reactions,
      hydroboration, hydroamination, hydrosilylation, and hydrofluorination. 

PMID- 25372413
TI  - Significance of selected antioxidant enzymes in cancer cell progression.
AB  - Antioxidant enzymes (AOEs), including superoxide dismutase isoenzymes (SOD),
      catalase (CAT), glutathione peroxidase (GSH-Px) along with glutathione reductase
      (GR), reduced glutathione (GSH) and glutathione transferase (GST), are thought to
      be necessary for life process in all oxygen-metabolizing cells by removing
      reactive oxygen species (ROS). The biological significance of AOEs in transformed
      cells is still unclear, but their capacity to survive may be affected by changes
      in cellular process such as proliferation, invasiveness, migration, apoptosis and
      drug resistance. This review summaries the significance of antioxidant enzymes in
      cancer cell progression mainly in an in vitro context.

PMID- 25372414
TI  - Pathologic diagnosis of antibody-mediated rejection in endomyocardial biopsy
      after heart transplantation based on renewed International Society for Heart and
      Lung Transplantation criteria.
AB  - Heart transplantation is a well-established life-saving treatment for patients
      presenting with end-stage cardiac failure. Despite improved efficacy of the
      procedure, allograft rejection continues to be a major cause of mortality and
      morbidity in cardiact allograft patients. Although acute cellular rejection (ACR)
      is quite unusual nowadays, acute antibody-mediated rejection (AMR) remains a
      significant problem. The role of pathologists in detection of AMR is very
      important, especially in sub-clinical cases. In 1990, histologic hallmarks of AMR
      were first stated by International Society for Heart and Lung Transplantation
      (ISHLT) and detailed histopathologic features and immunopathologic criteria were
      established in 2005. Recently (2013) ISHLT revised nomenclature and
      classification of AMR. Aim of this paper was to present practical changes coming
      from new criteria as well as to highlight difficulties concerning AMR assessment
      in endomyocardial biopsies (EMB). 

PMID- 25372415
TI  - Limited usefulness of histopathological features in identification of a
      clinically aggressive solid-pseudopapillary neoplasm of the pancreas.
AB  - Solid-pseudopapillary neoplasms (SPN) are rare tumours of the pancreas. Distant
      metastases and/or local recurrence following surgical resection occur in 10% to
      15% of patients with SPN. In the present study, we aimed to systematically
      examine the usefulness of virtually all histopathological features of SPN which
      were previously considered potential risk factors of clinically aggressive
      behaviour of SPN following surgical resection. Seventeen SPN were included. None
      of the cases had an undifferentiated component. Follow-up data were available for
      14 patients (median 52 months). One patient developed liver metastasis 17 months
      after resection of the primary tumour and fulfilled the criteria of a clinically
      aggressive disease. None of the histopathological features allowed identification
      of that case with an adequate diagnostic yield. At present, histopathological
      examination cannot identify patients who may develop tumour recurrence following
      resection of the primary lesion. A close follow-up should be offered to all
      patients treated for SPN. 

PMID- 25372416
TI  - Inverse correlation of phospho-KDR/Flk-1 expression and stage of colorectal
      cancer: implication of the significance of neoangiogenesis in activated VEGFR-2
      expressing early stage colorectal adenocarcinomas.
AB  - The activation of vascular endothelial cell growth factor receptors (VEGFRs)
      plays an essential role in cancer progression. In this study, we investigated the
      expression of phosphorylated VEGFR-2 (or phospho-KDR/Flk-1), the activated form
      of VEGFR-2, in human colorectal adenomas and colorectal adenocarcinomas. Phospho
      KDR/Flk-1 showed weak expression in the normal colorectal tissue. Phospho-KDR/Flk
      1 was mainly stained in the cytoplasm of colorectal adenomas, and was stained in
      both the cytoplasm and nuclei colorectal adenocarcinomas. There was no indication
      of increased phospho-KDR/Flk-1 expression in the colorectal adenocarcinomas, as
      compared to that of colorectal adenomas. Furthermore, there was an inverse
      relationship of phospho-KDR/Flk-1 expression with cancer stage (p < 0.0001),
      lymph node metastasis (p = 0.011), and distant metastasis (p = 0.021) of the
      colorectal adenocarcinomas. Our results indicate that early stage colorectal
      adenocarcinomas with highly activated (phosphorylated) VEGFR-2 expression may
      indicate the significance of neoangiogenesis of the tumors. 

PMID- 25372417
TI  - The value of tumor markers in the diagnosis of papillary thyroid carcinoma alone
      and in combination.
AB  - Aim of the study is to evaluate the expression of CK19, galectin-3, HBME-1, CD56,
      claudin-1 and neutrophil gelatinase-associated lipocalin (NGAL) in papillary
      thyroid carcinoma (PTC), including classic, follicular variant and micro
      carcinoma. Peritumoral benign thyroid tissues were used as a control (C).
      Immunohistochemical staining with the EnVision detection system was performed on
      59 formalin-fixed, paraffin-embedded thyroid tissues, including 43 PTC and 16 C.
      CK19, galectin-3, HBME-1, claudin-1 and NGAL were positive in most PTC, but were
      negative or showed focal weak staining in C. CD56 was positive in C, but absent
      in PTC. For a single analyzed tumor marker, the sensitivity of the above six
      thyroid tumor markers was 100%, 95.3%, 86%, 79.1%, 90.7%, 93%, respectively. The
      specificity was 56.25%, 100%, 100%, 100%, 100%, 100%, respectively. For the
      combination of the six tumor markers, the sensitivity, specificity, positive
      predictive value, negative predictive value and the diagnostic accuracy were all
      100%, with co-expression of at least four indices. In the diagnosis of PTC,
      combined application of the above tumor markers is recommended. It can be
      diagnosed as PTC clearly when thyroid lesions are positive for at least four of
      the above tumor markers [CD56-], and can be excluded as PTC definitely when at
      least four tumor markers are negative [CD56+].

PMID- 25372418
TI  - Degeneration and calcification of the cervical endplate is connected with
      decreased expression of ANK, ENPP-1, OPN and TGF-beta1 in the intervertebral
      disc.
AB  - The aim of this study was to clarify the relationship between the expression of
      ALP, ANK, ENPP-1, OPN and TGF-beta1 in the intervertebral disc (IVD), and
      cervical vertebral endplate calcification and degeneration. Sixty cervical IVDs
      were excised from 30 human cadavers. Each cadaver was assessed macroscopically
      for degeneration (Thompson's classification), and then underwent histological
      processing, regular staining (hematoxylin and eosin, Masson-Goldner trichrome and
      alcian blue-PAS), immunohistochemistry (ALP, ANK, ENPP-1, OPN and TGF-beta1),
      microscopic degeneration grading (Boos classification), and assessment of
      endplate calcification. The mean age +/- SD of the cadavers was 51.4 +/-19.5. The
      percentage of endplate calcification significantly correlated with the degree of
      endplate and IVD degeneration graded using Boos's score (both r = 0.91; p <
      0.0001). The intensity and number of stained cells per FOV markedly decreased,
      for ANK, ENPP-1, and TGF-beta1, with the grade of IVD degeneration, regardless of
      the analyzed IVD region. This was not true only for ALP, which demonstrated an
      increasing trend corresponding to the degree of IVD degeneration. The expression
      of OPN was low throughout all analyzed regions, regardless of the degree of
      degeneration. Modulating the expression of the abovementioned proteins,
      especially ANK and TGF-beta1, may be a new way to prevent degeneration and
      calcification of the IVD. 

PMID- 25372419
TI  - Renal tumors in unselected forensic post-mortem material.
AB  - The frequency of clinically evident renal tumors is increasing, due to an actual
      increase in incidence, but also due to an improvement in detection methods. The
      aim of the present study was to analyze the incidence of renal tumors in an
      unselected autopsy series. A search for renal tumors was conducted based on the
      autopsy reports from the Department of Forensic Medicine. The slides were
      reviewed and reclassified according to current criteria. Among 14,904 autopsies,
      80 renal tumors were found. The most frequent tumor types were clear cell
      carcinomas (41%), papillary carcinomas (18%) and cortical adenomas (19%). There
      were 66 males and 14 females. The average age was 57.83 for males and 62.86 for
      females. The characteristics of the study group were not exactly identical but
      similar to other autopsy series, and significantly different from surgical
      series. 

PMID- 25372420
TI  - Clinicopathological characteristics of segmental (IV-S) and global (IV-G) active
      subclasses of class IV lupus nephritis: a comparative study.
AB  - Class IV is the most common form of lupus nephritis (LN). This class is divided
      into diffuse segmental active subclass (IV-S/A) and diffuse global active
      subclass (IV-G/A). The purpose of the study was to compare the clinical data, and
      the incidence of glomerular active features in IV-S/A, and IV-G/A of LN. Of 34
      patients with class IV LN, 25 were classified as subclass IV-G/A, and 9 patients
      were included in subclass IV-S/A. Nephrotic syndrome and hypertension were
      significantly more frequent in patients in the IV-G/A subclass, whereas hematuria
      and low grade proteinuria were significantly more frequent in patients in the IV
      S/A subclass. Immunofluorescence findings revealed in group IV-S/A the presence
      of mesangial deposits and sparse deposits along the capillary wall. In contrast,
      an immunofluorescence study in subclass IV-G/A showed a preponderance of great
      subepithelial deposits. Fibrinoid necrosis of glomerular tufts was significantly
      more evident in subclass IV-S/A, whereas endocapillary hypercellularity, hyaline
      thrombi and wire loops were more frequent in subclass IV-G/A. The significant
      differences in clinical manifestation and in the incidence of histopathological
      active glomerular features between subclasses IV-S/A and IV-G/A of LN observed in
      our study may confirm the suggestion that these lesions have a different
      pathogenesis. 

PMID- 25372421
TI  - Value of perfusion CT parameters, microvessl density and VEGF expression in
      differentiation of benign and malignant prostate tumours.
AB  - The purpose of this study was to assess the correlation between parameters
      evaluated using computed tomography perfusion (CTP) and microvessel density
      (MVD), the vascular endothelial growth factor labelling index (VEGFLI), as well
      as known clinicopathological indicators of tumour malignancy, in non-advanced
      prostatic cancer. We included 110 patients with early stage prostate cancer who
      were subjected to CT examinations followed by radical prostatectomy between 2007
      and 2011 (in this analysis we included only patients diagnosed with CT). Both in
      affected and in healthy tissue the following perfusion parameters were assessed:
      blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability
      surface area product (PS). After surgery in the resected prostate tumour tissue
      the MVD and VEGFLI were assessed. The mean BF and PS values were significantly
      higher in carcinomas with high histological grade (p = 0.02). The sensitivity,
      specificity and accuracy of the threshold BF value, for the distinction between
      malignant and healthy prostate tissue, were: 67%, 54% and 59% respectively. For
      BV sensitivity was 71%, specificity was 52%, and accuracy was 48%. Microvessel
      density significantly correlated with BV, MTT and PS (p < 0.05), while VEGFLI did
      not correlate with any of the perfusion parameters. Our results suggest that BF
      and PS might be helpful in discrimination between benign and malignant prostate
      tissue, while the positive correlation between BV, MTT, PS and MVD might suggest
      their potential utility in assessment of cancer angiogenesis. 

PMID- 25372422
TI  - High-grade urothelial carcinoma, plasmacytoid variant, of the renal pelvis with
      osteoclast-like giant cells and focal rhabdoid features.
AB  - In this article, we present a rare case of renal pelvic carcinoma. The imaging
      examination of a 75-year-old Japanese man disclosed the left renal pelvic tumor.
      The histological examination showed the finding of predominant undifferentiated
      discohesive mononuclear cells with abundant osteoclast-like giant cells and a
      minor component of papillary urothelial carcinoma. Rhabdoid morphology was
      focally seen. Immunohistochemically, mononuclear cells were focally positive for
      thrombomodulin and showed a high MIB-1 index, whereas osteoclast-like giant cells
      were positive for CD68. Urologists should bear in mind that a rare association of
      high-grade urothelial carcinoma, plasmacytoid variant, with osteoclast-like giant
      cells and focal rhabdoid features may occur in the renal pelvis. 

PMID- 25372423
TI  - Malignant glomus tumor of the foot with obvious neuroendocrine differentiation: a
      case report with immunohistochemical studies.
AB  - Obvious neuroendocrine differentiation has not been reported in glomus tumor. The
      author herein reports a malignant glomus tumor of the foot showing obvious
      neuroendocrine differentiation. A 63-year-old woman presented with tumor of the
      left foot. The tumor was superficially seated, and located in the dermis. It was
      completely resected with wide margins. It measured 0.7 * 0.7 * 0.6 cm.
      Microscopically, the tumor was composed of atypical epithelioid cells located
      around blood vessel-like structures. The epithelioid cells showed relatively
      clear cytoplasm and severe cellular atypia, and resembled basal cell carcinoma.
      Focal areas of squamoid differentiation, carcinoid patterns, and neural
      differentiations were seen. There was no necrosis or atypical mitosis. However,
      mitotic figures were seen in 16 per 50 high-power-fields (HPF). The hematoxylin
      and eosin (HE) diagnosis was basosquamous carcinoma. Immunohistochemically, the
      tumor cells were strongly positive for vimentin, ?-smooth muscle actin, and
      neuron-specific enolase. The tumor was focally positive for NCAM, synaptophysin
      and chromogranin. The blood vessel-like structures had a layer of CD31- and CD34
      positive endothelial cells. Tp53 was positive and the Ki-67 labeling index was
      23%. The tumor cells were negative for cytokeratin (CK) AE1/3, CK CAM5.2, CK5,
      CK6, CK7, CK8, CK14, CK18, CK19, CK20, p63, EMA, CEA, CA19-9, desmin, myoglobin,
      HMB-45, Melan-A, S100 protein, MUC1, MUC2, MUC5AC, and MUC6. Taken together with
      HE histology, the tumor was labeled as malignant glomus tumor with neuronal
      differentiation, based on the classification system of Folpe et al. The post
      pathological diagnosis whole body examination using CT, MRI, PET, and endoscopies
      identified no tumors. The patient is now free from tumor and healthy 18 months
      after the resection. 

PMID- 25372424
TI  - Re: Co-existence of intramuscular spindle cell lipoma with an intramuscular
      ordinary lipoma: Report of a case Ivan Chernev, Shane Mctighe, Dirk P. Stanley.

PMID- 25372425
TI  - Sebaceous trichofolliculoma of the cheek in a 65-year-old man.
AB  - Sebaceous trichofolliculoma is considered as hamartomatous lesion with follicular
      differentiation. In this study, we demonstrated a classic histopathologic picture
      of sebaceous trichofolliculoma in a 65-year-old male presented with large sized
      right cheek swelling. 

PMID- 25372426
TI  - Probing the nanostructure, interfacial interaction, and dynamics of chitosan
      based nanoparticles by multiscale solid-state NMR.
AB  - Chitosan-based nanoparticles (NPs) are widely used in drug and gene delivery,
      therapy, and medical imaging, but a molecular-level understanding of the internal
      morphology and nanostructure size, interface, and dynamics, which is critical for
      building fundamental knowledge for the precise design and efficient biological
      application of the NPs, remains a great challenge. Therefore, the availability of
      a multiscale (0.1-100 nm) and nondestructive analytical technique for examining
      such NPs is of great importance for nanotechnology. Herein, we present a new
      multiscale solid-state NMR approach to achieve this goal for the investigation of
      chitosan-poly(N-3-acrylamidophenylboronic acid) NPs. First, a recently developed
      (13)C multiple cross-polarization magic-angle spinning (MAS) method enabled fast
      quantitative determination of the NPs' composition and detection of
      conformational changes in chitosan. Then, using an improved (1)H spin-diffusion
      method with (13)C detection and theoretical simulations, the internal morphology
      and nanostructure size were quantitatively determined. The interfacial
      coordinated interaction between chitosan and phenylboronic acid was revealed by
      one-dimensional MAS and two-dimensional (2D) triple-quantum MAS (11)B NMR.
      Finally, dynamic-editing (13)C MAS and 2D (13)C-(1)H wide-line separation
      experiments provided details regarding the componential dynamics of the NPs in
      the solid and swollen states. On the basis of these NMR results, a model of the
      unique nanostructure, interfacial interaction, and componential dynamics of the
      NPs was proposed. 

PMID- 25372427
TI  - Spontaneous closure of an idiopathic macular hole 9 months after unsuccessful
      vitreoretinal surgery.
AB  - PURPOSE: To report spontaneous closure of a persistent idiopathic macular hole
      (MH) 9 months after cataract and vitreoretinal surgery, and subsequent gas
      reinjection. METHODS: Baseline and follow-up examinations after surgery included
      slit-lamp biomicroscopy, best-corrected distance visual acuity and near visual
      acuity, spectral domain optical coherence tomography, and microperimetry.
      RESULTS: Spectral domain optical coherence tomography scans showed a persistent
      MH after surgery until 5 months of follow-up, with an increasing base diameter of
      the MH and decreasing best-corrected visual acuity. Nine months after surgery,
      spontaneous closure of the MH with an improvement in best-corrected visual acuity
      was observed. These findings remained stable at 15 months of follow-up, with an
      additional increase in retinal sensitivity. CONCLUSION: Spontaneous closure of a
      persistent Stage 3 full-thickness MH after primary surgery is possible. We
      recommend follow-up examinations including spectral domain optical coherence
      tomography for several months before scheduling a reoperation.

PMID- 25372428
TI  - Spontaneous resolution of a postvitrectomy macular hole retinal detachment.
AB  - PURPOSE: The purpose of this report was to describe a case of spontaneous
      resolution of a large postvitrectomy macular hole retinal detachment. METHODS:
      Case report and optical coherence tomography imaging. RESULTS: A 64-year-old man
      with history of macula-off retinal detachment and 4 previous vitrectomies in the
      left eye developed a macular hole and associated retinal detachment 3 months
      after his last vitreoretinal surgery. Two months later, examination revealed that
      the macular hole had spontaneously closed, and the retinal detachment had
      resolved. CONCLUSION: Spontaneous resolution of macular hole-associated retinal
      detachment in a previously vitrectomized eye has not been reported previously.
      Changes in tangential traction by the associated epiretinal membrane, improvement
      of the cystoid changes noted at the edge of the macular hole, and/or
      proliferation of glial tissue to bridge the hole, along with the absorption of
      the subretinal fluid by the retinal pigment epithelium pump contributed to this
      rare event have been hyphothesized.

PMID- 25372429
TI  - Vitamin A deficiency and xerophthalmic fundus in autoimmune hepatitis and
      cirrhosis.
AB  - PURPOSE: To report a patient with autoimmune hepatitis and cirrhosis who was
      diagnosed with severe vitamin A deficiency based on the findings of xerophthalmic
      fundus. METHODS: Retrospective chart review. PATIENT: A 36-year-old African
      American woman who had a history of autoimmune hepatitis and cirrhosis presents
      with peripheral retinal white spots, which led to the diagnosis of vitamin A
      deficiency. RESULTS: The patient presented to the eye clinic for intermittent
      blurry vision 3 months after the diagnosis of liver cirrhosis secondary to
      autoimmune hepatitis since age 15. She also underwent partial large and small
      intestine resection as an infant for Hirschsprung disease. Anterior segment
      examination was significant for severe punctate epithelial erosions and posterior
      segment examination was significant for extensive white spots in the peripheral
      retina in both eyes. Workup showed near nondetectable levels of vitamin A (<0.06
      mg/L, normal 0.3-1.2 mg/L) and retinyl palmitate (<0.02 mg/L, normal > 0.2 mg/L).
      After treatment with 200,000 IU of vitamin A orally, the white spots slowly
      resolved in ~6 months. She never developed nyctalopia and her dry eye symptoms
      completely resolved. CONCLUSION: Although rare, vitamin A deficiency should be
      considered in patients with liver cirrhosis especially in those with a history of
      intestinal surgeries. Early diagnosis and treatment with vitamin A
      supplementation can reverse the signs and symptoms of xerophthalmia.

PMID- 25372430
TI  - Treatment of recalcitrant radiation maculopathy using intravitreal dexamethasone
      (Ozurdex) implant.
AB  - PURPOSE: Radiation maculopathy is the most common cause of severe vision loss
      after radiotherapy of uveal melanoma. To date, no effective therapy exists. The
      authors report a novel approach to the treatment of radiation maculopathy using
      dexamethasone (Ozurdex, Allergan Inc) intravitreal implant. METHODS: This is a
      retrospective case series of two patients who developed radiation maculopathy
      after radiotherapy for uveal melanoma and was treated with Ozurdex. Clinical
      outcomes included visual acuity, central foveal thickness by optical coherence
      tomography, intraocular pressure, and cataract formation. RESULTS: Both patients
      were of Caucasian descent. Patient 1 received charged-particle radiation, whereas
      Patient 2 received iodine-125 brachytherapy for medium-sized uveal melanoma
      located in the midperipheral retina. Radiation maculopathy developed 47 months
      and 18 months after radiation exposure in Patient 1 and 2, respectively. Both
      patients initially received bevacizumab monotherapy followed by alternating
      therapy with bevacizumab and intravitreal triamcinolone. Secondary to a limited
      response, the patients were treated with Ozurdex implants. One patient had visual
      improvement, and both patients experienced a prolonged time frame of anatomical
      stability. Adverse effects included a rise in the intraocular pressure, which was
      controlled by topical hypotensive agents and posterior subcapsular cataract
      formation in Patient 1. CONCLUSION: Ozurdex intravitreal implant provides a
      prolonged period of anatomical stabilization in recalcitrant cases of radiation
      maculopathy in patients who have failed multiple intravitreal bevacizumab
      injections and had only a partial response to intravitreal triamcinolone. Larger
      prospective studies are required to determine the extent of visual benefit.

PMID- 25372431
TI  - Subarachnoid hemorrhage-negative Terson syndrome after balloon-assisted coil
      embolization in a patient with underlying antiphospholipid antibody syndrome.
AB  - PURPOSE: To report subarachnoid hemorrhage-negative Terson syndrome after coil
      embolization of an unruptured intracranial aneurysm in a patient with underlying
      antiphospholipid syndrome. METHODS: Retrospective case report. A 48-year-old
      woman with underlying antiphospholipid syndrome. RESULTS: Our patient underwent
      balloon-assisted coil embolization of an unruptured right internal carotid artery
      aneurysm. There was herniation of the second coil requiring coil retrieval with
      subsequent nonflow limiting herniation of the first coil left in situ on
      anticoagulation. In the immediate postprocedure period, she developed preretinal,
      intraretinal, and vitreous hemorrhages requiring temporary withholding of
      anticoagulation therapy with careful resumption. Visual acuity was counting
      fingers and there was an afferent pupillary defect. Two week after discharge, the
      patient underwent a pars plana vitrectomy for dense breakthrough vitreous
      hemorrhage. Four weeks after pars plana vitrectomy, her visual acuity was 20/400.
      CONCLUSION: Terson syndrome should be considered in a patient with visual
      symptoms after not only aneurysmal subarachnoid hemorrhage but also non
      subarachnoid hemorrhage elective aneurysm coiling as demonstrated by our case.

PMID- 25372432
TI  - Spontaneous choroidal hemorrhage in a patient on dabigatran etexilate (Pradaxa).
AB  - PURPOSE: To report the first known case of spontaneous choroidals in association
      with a patient on dabigatran etexilate. METHODS: Observational case report.
      RESULTS: An 82-year-old man on 150 mg dabigatran etexilate by mouth twice a day
      for atrial fibrillation developed spontaneous choroidal hemorrhage in his left
      eye. No other causes were found after careful history and examination.
      CONCLUSION: Dabigatran is a popular new alternative to warfarin that has no blood
      monitoring or reversal agent. Physicians should be aware of this new medication
      and its possible hemorrhagic complications.

PMID- 25372433
TI  - Salvaging recurrent scleral buckle exposure with autologous periosteal patch
      graft.
AB  - PURPOSE: To describe a surgical technique for salvaging recurrent exposure of
      scleral buckle. METHODS: A patient, treated for rhegmatogenous retinal detachment
      with scleral buckle, presented with exposed uninfected buckle 3 weeks after the
      initial surgery. We tried to cover the exposure twice with conjunctivoplasty and
      once with scleral patch graft with amniotic membrane transplantation, but each
      one of them failed. After these failed attempts, we harvested autologous
      periosteal patch graft from the retroauricular area, which was sutured over the
      exposed buckle along with conjunctivoplasty. RESULTS: Autologous periosteal patch
      graft was successful in our case and reepithelialization was completed within 4
      weeks. A small granuloma was formed at the suture site at the fifth week, which
      resolved completely with topical steroids. The conjunctiva and periosteal patch
      have remained stable over a follow-up period of 1 year. The autologous periosteal
      patch graft permanently covered the defect with complete reepithelialization by 4
      weeks after the surgical procedure. CONCLUSION: Autologous periosteal patch graft
      can be offered as a viable alternative option to the patients with scleral buckle
      exposure.

PMID- 25372434
TI  - Long-term hypotony because of accidental break of a 23 g microcannula after
      transconjunctival sutureless vitrectomy.
AB  - PURPOSE: To report a case of long-lasting hypotony because of accidental break,
      with scleral tunnel entrapment, of a 23-gauge microcannula during
      transconjunctival sutureless vitrectomy. METHODS: Interventional case report. An
      80-year-old Spanish woman who underwent 23-gauge transconjunctival sutureless
      vitrectomy presented at the postoperative ocular examination with irreversible,
      refractory low intraocular pressure of unknown cause. Two weeks after surgery, a
      piece of the microcannula was found at the inferotemporal sclerotomy site during
      a scheduled medical appointment. Surgical intervention was indicated to explore
      and remove the foreign body. RESULTS: The day after foreign body extraction, the
      patient's pressure rose to normal levels. However, her visual acuity did not
      improve until 3 weeks later. CONCLUSION: Transient postoperative hypotony is
      unsurprising after 23-gauge vitrectomy because of leakage of small-diameter open
      sclerotomies. However, when long-term low intraocular pressure fails to return to
      normal levels because of an unidentified condition, breaking of the microcannula
      piece with scleral tunnel entrapment may be contemplated.

PMID- 25372435
TI  - Central retinal artery occlusion and Susac syndrome: a case report.
AB  - BACKGROUND: Susac syndrome is a rare disease attributed to microangiopathy
      involving the arterioles of the brain, retina, and cochlea. Understanding the
      pathogenesis is incomplete, but an immune-mediated process remains the leading
      hypothesis. METHODS: Report of a single case of a previously healthy 22-year-old
      female patient showing the complete clinical triad. RESULTS: Diagnosis of Susac
      syndrome in this patient was first questioned due to the atypical initial
      ophthalmologic presentation with central retinal artery occlusion. Multiple
      relapses occurred in the fellow eye during follow-up, showing the typical branch
      retinal artery occlusions, allowing definite diagnosis. CONCLUSION: Susac
      syndrome should be considered in the differential diagnosis when facing (young)
      patients with central retinal artery occlusion, especially in the presence of
      unexplained encephalopathy and/or sensorineural hearing loss.

PMID- 25372436
TI  - Endoscopic cyclophotocoagulation in refractory glaucoma after osteo-odonto
      keratoprosthesis in Stevens-Johnson syndrome: a case report.
AB  - PURPOSE: To report successful treatment of refractive glaucoma in a patient
      submitted to osteo-odonto-keratoprosthesis surgery for Stevens-Johnson syndrome.
      METHODS: An interventional case report. RESULTS: The patient is a 62-year-old
      Indian man with known Stevens-Johnson syndrome since 1972 secondary to
      tetracycline therapy, with bilateral dry eye and corneal blindness. He underwent
      symblepharon release surgery with mucous membrane graft in both eyes. Osteo
      odonto-keratoprosthesis surgery was later performed on the left eye. He was
      submitted to 2 Ahmed valve implants to control secondary glaucoma but visual
      fields continued to worsen; hence, he underwent endoscopic 140 degrees 
      cyclophotocoagulation with a good control of IOP. CONCLUSION: Endoscopic
      cyclophotocoagulation as alternative treatment provides good results in
      refractory glaucoma after osteo-odonto-keratoprosthesis surgery.

PMID- 25372437
TI  - Chronic endophthalmitis due to Pyrenocheta romeroi in an immunocompetent host--a
      case report from southern India.
AB  - PURPOSE: Endophthalmitis due to Pyrenochaeta romeroi has not been reported in
      literature (PubMed, Medline). We report an interesting case of P. romeroi causing
      chronic endophthalmitis in an immunocompetent lady. METHODS: Retrospective
      interventional case report. A 25-year-old immunocompetent lady presented with
      pain and redness in the left eye of 1-month duration. Her best-corrected visual
      acuity was 6/6 and 6/18 in the right and the left eyes, respectively. Slit-lamp
      examination of the left eye showed a corneal stromal scar, fibrinlike material in
      the anterior chamber, few retrolental cells, and normal fundus examination.
      RESULTS: Aqueous taps on two occasions were negative for bacteria and fungi on
      routine smear, culture, and nested polymerase chain reaction. As inflammation
      recurred despite intravitreal voriconazole and amikacin injections, a lensectomy
      with vitrectomy was done. During vitrectomy, dense flocculent material was seen
      in the pars plana with only scleral indentation. The flocculent material grew a
      rare filamentous fungus called P. romeroi. The left eye underwent retinal
      detachment surgery with silicone oil insertion for a giant retinal tear at 2
      months of follow-up. At 6 months of follow-up, her vision in the left eye was
      stable at 6/24 (Snellen) with no ocular inflammation. CONCLUSION: P. romeroi may
      need to be added in the list of rare fungi, which cause chronic endophthalmitis.

PMID- 25372438
TI  - Acute exudative polymorphous vitelliform maculopathy in a young man: a case
      report.
AB  - PURPOSE: To describe ocular findings consistent with acute exudative polymorphous
      vitelliform maculopathy in a healthy 34-year-old man. METHODS: Observational case
      report of a patient presenting with blurred vision in the left eye greater than
      the right eye. RESULTS: Funduscopic examination and fluorescein angiography were
      consistent with acute exudative vitelliform maculopathy, a rare exudative macular
      disorder. Five months after presentation, the patient was diagnosed with
      metastatic melanoma. CONCLUSION: A case is reported in a young man with no
      diagnosis of primary neoplasm at the time of presentation, and no other symptoms
      overall, who was later diagnosed with a metastatic malignancy.

PMID- 25372439
TI  - Nonsupine positioning is preferred by patients over face-down positioning and
      provides an equivalent closure rate in 25- and 23-gauge macular hole surgery.
AB  - PURPOSE: Strict face-down positioning after macular hole surgery is very
      difficult for most patients. Our study seeks to determine if alleviated
      positioning (avoidance of supine positioning) has equivalent successful closure
      rates when compared with face-down positioning. A patient survey was also
      performed to determine patient preference. METHODS: A single-center retrospective
      review of patients undergoing macular hole repair with a questionnaire completed
      by each patient after air bubble clearance summarizing the two postoperative
      scenarios. Patients were asked which positioning strategy they would choose if
      they were having repeat surgery. Eighty-two patients undergoing pars plana
      vitrectomy with primary full-thickness macular hole repair were identified.
      Repair was performed with either 3 days of strict face-down positioning (57 of 82
      patients) or with the avoidance of supine positioning (25 of 82 patients) but no
      required face-down positioning. RESULTS: The anatomical success rates were
      similar between the 2 groups with 96% of final hole closure (55/57) in the face
      down group versus 100% (25/25) in the nonsupine group. Macular hole size appeared
      to be similar between the 2 groups (a mean of 408 MUm in face-down group vs. that
      of 483 MUm in nonsupine group, with a median of 400 in both groups). Patient
      preference was in favor of less stringent nonsupine postoperative requirements.
      Although 100% (25/25) of the nonsupine group would opt for the same strategy with
      repeat surgery, only 51% (29/57) of the face-down group would opt for face-down
      positioning with repeat surgery (P < 0.001). CONCLUSION: This study demonstrates
      equivalent closure rates among the patients who were assigned nonsupine versus
      face-down positioning postoperatively for macular hole repair, and that most
      patients would prefer to avoid strict face-down positioning if reoperated.

PMID- 25372440
TI  - Posterior segment involvement in Castleman disease.
AB  - PURPOSE: We present here a patient with Castleman disease, a rare
      lymphoproliferative disorder, involving the vitreous. Her clinical findings are
      described. METHODS: Retrospective case study with slit-lamp photographs. A 28
      year-old woman with known Castleman disease presented with visual complaints. Her
      ophthalmic findings are described. RESULTS AND CONCLUSION: Based on literature
      searches, this is the first reported patient with Castleman disease having
      putative involvement of the vitreous body.

PMID- 25372441
TI  - Bilateral perifoveal macular ischemia in sarcoidosis.
AB  - PURPOSE: To represent and evaluate the findings of bilateral perifoveal macular
      ischemia in a patient with biopsy-proven, multiorgan involved sarcoidosis.
      METHODS: Case report. A 55-year-old man, with a medical history of pulmonary
      disease, experienced reduced vision bilaterally. General ocular examination,
      fundus color photographs, fluorescence angiography, and high-resolution spectral
      domain optical coherence tomography were performed in both eyes. RESULTS: The
      patient's visual acuity was 20/200 in the right eye and 20/30 in the left eye
      with normal intraocular pressure and anterior segment. Fundus examination showed
      symmetric changes with the loss of transparency in macular and small intraretinal
      hemorrhages in both eyes. Fluorescence angiography demonstrated markedly enlarged
      avascular zone while optical coherence tomography revealed marked cystic change
      in the macula bilaterally. A series of blood test was conducted without a
      specific diagnosis. A lung biopsy confirmed the diagnosis of pulmonary
      sarcoidosis, and a magnetic resonance imaging of his brain revealed
      neurosarcoidosis. CONCLUSION: Bilateral perifoveal ischemia, formerly one of the
      three idiopathic macular telangiectasia diseases, is rare and usually suggests a
      systemic etiology. It is not unexpected that sarcoidosis, a multisystem, chronic
      inflammatory disorder, may affect retinal vessels and be associated with this
      peculiar form of ischemia and edema.

PMID- 25372442
TI  - Sequential spectral domain optical coherence tomography imaging of an eye after
      successful removal of subfoveal perfluorcarbon liquid collection.
AB  - PURPOSE: To evaluate retinal restoration after subfoveal perfluorcarbon liquid
      (PFCL) bubble removal by means of autofluorescence, infrared, and spectral domain
      optical coherence tomography over 2 years of follow-up. METHODS: A 62-year-old
      patient underwent two 23-gauge vitrectomies in attempt to remove subretinal PFCL
      retained under the fovea secondary to retinal detachment surgery in the left eye.
      We assessed best-corrected visual acuity, fundus biomicroscopy, retinal imaging
      by autofluorescence, infrared, and spectral domain optical coherence tomography
      at the first observation of retained PFCL, 1 day after the first attempt of PFCL
      removal, and 1, 30, 90, and 180 days, and 2 years after the second successful
      removal surgery. RESULTS: The best-corrected visual acuity improved from 5 to 45
      Early Treatment of Diabetic Retinopathy Study letters (1.0 to 0.2 logMAR units)
      at the end of follow-up. Spectral domain optical coherence tomography scans
      showed progressive reorganization of the outer limiting membrane and significant
      restoration of the inner/outer segment photoreceptors junction 2 years after
      surgery. CONCLUSION: Subfoveal PFCL is believed to cause photoreceptor damage in
      some eyes, probably because of mechanical compression. Innovative methods of
      imaging such as spectral domain optical coherence tomography and confocal
      scanning laser ophthalmoscope with infrared and autofluorescence, allow early and
      clear detection of subfoveal retained PFCL, as well as careful follow-up and easy
      differential diagnosis. Surgical removal leads to prompt retinal morphologic
      restoration and functional improvement enduring over time.

PMID- 25372443
TI  - Proliferative ischemic retinopathy after arteriovenous malformation embolization
      in a child with hereditary hemorrhagic telangiectasia.
AB  - PURPOSE: To describe a case of hereditary hemorrhagic telangiectasia, presenting
      with multiple branch retinal artery occlusions, retinal ischemia,
      neovascularization, and vitreous hemorrhage after cerebral arteriovenous
      malformation embolization. METHODS: The authors report a 7-year-old patient with
      decreased vision in his left eye after embolization of a pineal arteriovenous
      malformation secondary to hereditary hemorrhagic telangiectasia. Ophthalmic
      evaluation, fundus photography, fluorescein angiography, spectral domain optical
      coherence tomography, electroretinogram, examination under anesthesia, and pars
      plana vitrectomy (PPV) were performed. RESULTS: Fundus examination of the left
      eye revealed extensive posterior segment ischemia, vascular tortuosity, and
      vitreous hemorrhage. Fluorescein angiography was remarkable for partial
      obstruction of retinal arteries, midperipheral nonperfusion, and associated
      leakage from multiple areas of neovascularization. Spectral domain optical
      coherence tomography was normal. Electroretinogram demonstrated decreased b-wave
      amplitude. The patient was subsequently treated with 25-gauge pars plana
      vitrectomy, panretinal endophotocoagulation, and intravitreal bevacizumab. Five
      weeks after surgery, best-corrected visual acuity had improved to 20/40, and
      examination showed resolution of vitreous hemorrhage and neovascularization.
      CONCLUSION: Retinal vascular abnormalities, posterior segment ischemia, and
      vitreous hemorrhage suggested a combination of retinal involvement of hereditary
      hemorrhagic telangiectasia complicated by nontarget embolization.

PMID- 25372444
TI  - Three cases of rhegmatogenous retinal detachment associated with regressed
      retinoblastoma after conservative tumor therapy.
AB  - PURPOSE: To report three cases of rhegmatogenous retinal detachment associated
      with regressed retinoblastoma after conservative therapy. METHODS: Three eyes of
      three patients with rhegmatogenous retinal detachment, in which retinal breaks
      were present at the edge of the tumor scar, were treated with vitrectomy and
      scleral buckling. RESULTS: In two eyes, in which cryopexy and silicone oil
      injection were performed, a preretinal membrane was formed that was comprised
      primarily of glial cells. Additional vitrectomy and membrane peeling reattached
      the retina. In one eye, in which photocoagulation and gas injection were
      performed, an initial vitrectomy and scleral buckling reattached the retina
      without postoperative membrane formation. CONCLUSION: Vitrectomy and scleral
      buckling contributed to closure of the irregularly shaped retinal tear at the
      edge of the tumor scar. Photocoagulation and gas injection instead of cryopexy
      and silicone oil injection may avoid postoperative glial proliferation from the
      tumor scar.

PMID- 25372445
TI  - Intraocular intrusion of suture material that was used as scleral buckling
      material.
AB  - PURPOSE: To report intrusion of encircling suture used for scleral buckling 20
      years ago. METHODS: Observational case report of a patient who admitted with the
      complaint of floaters. The patient had surgery for retinal detachment 20 years
      ago. Fundus examination revealed an encircling suture material. In some
      locations, the encircling suture had eroded all the way through the sclera to the
      vitreous cavity. In these locations, it was passing through the vitreous cavity.
      There was no retinal detachment, inflammation, or hemorrhage. RESULTS:
      Prophylactic argon laser photocoagulation was performed. No complication occurred
      during 1-year follow-up. CONCLUSION: A conservative approach with close follow-up
      may be suitable in case of an intrusion of suture material if there are no
      accompanying complications.

PMID- 25372446
TI  - Late retinal neovascularization after central retinal vein occlusion: a case
      report and literature review.
AB  - PURPOSE: To present the case of a 59-year-old man with central retinal vein
      occlusion with limited retinal ischemia who developed retinal neovascularization
      over a year after initial presentation. METHODS: Retrospective case report.
      RESULTS: On initial presentation, the patient had counting fingers vision in the
      affected eye and significant macular edema. After 4 intravitreal ranibizumab
      injections, his vision improved to 20/30. An intravenous fluorescein angiography
      performed at presentation and at a 4-month follow-up revealed limited retinal
      ischemia and no neovascularization. Over a year after his initial presentation,
      the patient returned with visual symptoms and was found to have subhyaloid
      hemorrhage and areas of retinal neovascularization. CONCLUSION: Anterior and
      posterior segment neovascularization after central retinal vein occlusion has
      traditionally been thought to occur within a few months of the inciting event.
      However, the use of antivascular endothelial growth factor agents may alter the
      angiogenic processes within an eye after central retinal vein occlusion,
      potentially delaying the onset of neovascularization. This suggests the need for
      enhanced monitoring in this patient population.

PMID- 25372447
TI  - Oxidation of ascorbic acid by a (salen)ruthenium(VI) nitrido complex in aqueous
      solution.
AB  - The oxidation of ascorbic acid (H2A) by [Ru(VI)(N)(L)(MeOH)](+) in aqueous acidic
      solutions has the following stoichiometry: 2[Ru(VI)(N)] + 3H2A -> 2[Ru(III)(NH2
      HA)](+) + A. Mechanisms involving HAT/N-rebound at low pH (<=2) and nucleophilic
      attack at the nitride at high pH (>=5) are proposed. 

PMID- 25372448
TI  - Twist and turn: effect of stereoconfiguration on the interfacial assembly of
      polyelectrolytes.
AB  - Understanding the conditions that promote the adsorption, assembly, and
      accumulation of charged macromolecules at the interface between aqueous and
      hydrophobic liquids is important to a multitude of biological, environmental, and
      industrial processes. Here, the oil-water interfacial behavior of stereoisomers
      of polymethacrylic acid (PMA), a model system for both naturally occurring and
      synthetic polyelectrolytes, is investigated with a combination of vibrational sum
      frequency (VSF) spectroscopy, surface tension, and computations. Syndiotactic and
      isotactic isomers both show rapid adsorption to the oil-water interface with a
      net orientation indicative of a high degree of ordering. The stereoconfiguration
      is found to affect whether only a single layer or multiple layers assemble at the
      interface. Surface tension measurements show additional adsorption for
      syndiotactic PMA over time. The additional layers do not contribute to the VSF
      spectrum indicating disorder in all but the initial layer. The isotactic isomer
      shows no evidence of accumulation at the interface beyond the single ordered
      layer. Molecular dynamics calculations show marked differences between the two
      isomers in the orientation of their substituent groups at the interface. The
      hydrophilic and hydrophobic moieties in the isotactic isomer are easily
      partitioned to the water and oil phases, respectively, whereas a fair portion of
      hydrophobic groups remain in the water phase for the syndiotactic PMA. The
      available hydrophobic contacts in the water phase at the interface are credited
      with allowing further adsorption. 

PMID- 25372450
TI  - Purse-string suture vs second intention healing: results of a randomized, blind
      clinical trial.
AB  - IMPORTANCE: Purse-string suture is a closure method that purportedly reduces the
      scar area compared with second intention healing. Randomized clinical trials
      comparing these 2 methods appear to be limited or absent. OBJECTIVE: To determine
      if purse-string suture improves cosmetic outcome, healing time, and scar to
      defect area compared with second intention healing for circular defects on the
      trunk and extremities. DESIGN, SETTING, AND PARTICIPANTS: Prospective, 2-arm,
      randomized, evaluator-blinded clinical trial in a single-center outpatient
      academic dermatology center. Patients were eligible if they were older than 18
      years, able to give informed consent, and had circular or oval postoperative
      defects larger than 8 mm on the trunk or extremities. INTERVENTIONS: For the
      purse-string treatment arm, wounds were sewn in circumferential fashion using
      polydiaxanone suture. Patients in the other treatment arm were allowed to heal by
      second intent. MAIN OUTCOMES AND MEASURES: The primary outcome measures were the
      mean total Patient and Observer Scar Assessment Scale (POSAS) scores ascertained
      from the patient and 2 blinded observers. Secondary outcomes included the ratio
      of scar to initial defect size, healing time, pain scores, and complication
      rates. RESULTS: Fifty-two patients were screened, and a total of 44 patients with
      50 surgical sites were enrolled. Forty-two patients with 48 surgical sites
      completed the study. The mean total observer POSAS score was 18.38 for the purse
      string group vs 19.91 for the secondary intention group, a nonsignificant
      difference (P = .41). Similarly, there were no significant differences for any of
      the following secondary outcome measures: mean total patient POSAS score (P =
      .96), mean scar-to-defect area (P = .61), and mean pain level at week 1 (P =
      .19). Statistical trends toward significance were seen in the mean healing time
      in favor of purse-string suture (P = .10) and scar relief, which favored second
      intention healing (P = .07). CONCLUSIONS AND RELEVANCE: The purse-string suture
      results in similar cosmetic outcomes, scar sizes, and pain levels compared with
      second intention healing for circular or oval wounds on the trunk and
      extremities. A larger study might better define the potential differences in our
      secondary outcome measures of healing time and scar relief. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT02062866.

PMID- 25372451
TI  - Using electronic health records for surgical quality improvement in the era of
      big data.
AB  - IMPORTANCE: Risk adjustment is an important component of quality assessment in
      surgical health care. However, data collection places an additional burden on
      physicians. There is also concern that outcomes can be gamed depending on the
      information recorded for each patient. OBJECTIVE: To determine whether a number
      of machine-collected data elements could perform as well as a traditional full
      risk adjustment model that includes other physician-assessed and physician
      recorded data elements. DESIGN, SETTINGS, AND PARTICIPANTS: All general surgery
      patients from the National Surgical Quality Improvement Program database from
      January 1, 2005, to December 31, 2010, were included. Separate multivariate
      logistic regressions were performed using either all 66 preoperative risk
      variables or only 25 objective variables. The area under the receiver operating
      characteristic curve (AUC) of each regression using objective preoperative risk
      variables was compared with its corresponding regression with all preoperative
      variables. Subset analyses were performed among patients who received certain
      operations. MAIN OUTCOMES AND MEASURES: Mortality or any surgical complication
      captured by the National Surgical Quality Improvement Program, both inpatient and
      within 30 days postoperatively. RESULTS: Data from a total of 745 053 patients
      were included. More than 15.8% of patients had at least 1 complication and the
      mortality rate was 2.8%. When examining inpatient mortality, the AUC was 0.9104
      with all 66 variables vs 0.8918 with all 25 objective variables. The difference
      in AUC comparing models with all variables with objective variables ranged from 
      0.0073 to 0.1944 for mortality and 0.0198 to 0.0687 for complications. In models
      predicting mortality, the difference in AUC was less than 0.05 among all patients
      and subsets of patients with abdominal aortic aneurysm repair, pancreatic
      resection, colectomy, and appendectomy. In models predicting complications, the
      difference in AUC was less than 0.05 among all patients and subsets of patients
      with pancreatic resection, laparoscopic cholecystectomy, colectomy, and
      appendectomy. CONCLUSIONS AND RELEVANCE: Rigorous risk-adjusted surgical quality
      assessment can be performed solely with objective variables. By leveraging data
      already routinely collected for patient care, this approach allows for wider
      adoption of quality assessment systems in health care. Identifying data elements
      that can be automatically collected can make future improvements to surgical
      outcomes and quality analyses.

PMID- 25372452
TI  - Surgical site infection in surgery for benign prostatic hyperplasia: comparison
      of two skin antiseptics and risk factors.
AB  - BACKGROUND: Surgical site infection (SSI) is the second most common type of
      nosocomial infections in the United States. In Uruguay, the incidence after
      prostatectomies is 2.6%. The aim of our study was to compare the efficacy of two
      skin antiseptics and to determine possible risk factors for SSI in patients
      undergoing surgery for benign prostatic hyperplasia (BPH). METHODS: A randomized
      trial included 70 patients operated on for BPH, of whom 56 (80%) underwent open
      surgery. Patients were treated by the same surgical team in a tertiary general
      hospital that is a referral center for patients with urologic diseases. Skin
      antisepsis was performed randomly using either 0.5% povidone-iodine or
      chlorhexidine in an alcohol base (Chemisol((r))). Possible risk factors
      investigated were age, renal dysfunction, bladder stones, preoperative urinary
      catheter, positive preoperative urine culture, operative time and technique, and
      vesicocutaneous fistula. RESULTS: Of all patients, 41 (59%) had a urinary
      catheter preoperatively. Urine cultures were positive in 31 patients, of whom 29
      (94%) had a urinary catheter. Surgical site infection occurred in 10 patients
      (18%), and 100% of the causative microorganisms were gram-negative bacteria
      characteristic of the urinary flora. The type of antiseptic did not affect the
      risk of SSI (p=1.00). The most important risk factor for infection was the
      presence of a urinary catheter preoperatively (p=0.003); also significant were
      the formation of a vesicocutaneous fistula (p=0.008), increasing age (p=0.02),
      and the presence of a positive preoperative urine culture (p=0.03). CONCLUSIONS:
      In a cohort of patients submitted to open prostatectomy, SSI was not related to
      the type of antiseptic. The main risk factor was the presence of a urinary
      catheter preoperatively. All microorganisms isolated from the SSIs were
      characteristic of urinary tract infections.

PMID- 25372453
TI  - Evaporation of sessile droplets affected by graphite nanoparticles and binary
      base fluids.
AB  - The effects of ethanol component and nanoparticle concentration on evaporation
      dynamics of graphite-water nanofluid droplets have been studied experimentally.
      The results show that the formed deposition patterns vary greatly with an
      increase in ethanol concentration from 0 to 50 vol %. Nanoparticles have been
      observed to be carried to the droplet surface and form a large piece of
      aggregate. The volume evaporation rate on average increases as the ethanol
      concentration increases from 0 to 50 vol % in the binary mixture nanofluid
      droplets. The evaporation rate at the initial stage is more rapid than that at
      the late stage to dry, revealing a deviation from a linear fitting line, standing
      for a constant evaporation rate. The deviation is more intense with a higher
      ethanol concentration. The ethanol-induced smaller liquid-vapor surface tension
      leads to higher wettability of the nanofluid droplets. The graphite nanoparticles
      in ethanol-water droplets reinforce the pinning effect in the drying process, and
      the droplets with more ethanol demonstrate the depinning behavior only at the
      late stage. The addition of graphite nanoparticles in water enhances a droplet
      baseline spreading at the beginning of evaporation, a pinning effect during
      evaporation, and the evaporation rate. However, with a relatively high
      nanoparticle concentration, the enhancement is attenuated. 

PMID- 25372454
TI  - Low-level laser therapy on bone repair of rat tibiae exposed to ionizing
      radiation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of low-level
      laser therapy (LLLT) on the repair of rat tibiae exposed to ionizing radiation
      (IR). BACKGROUND DATA: IR causes structural changes that delay bone tissue
      repair. Properly dosed, LLLT improves the bone repair process. METHODS: Seventy
      two healthy Wistar rats were distributed into the following groups: Group I, sham
      control; Group II, LLLT; Group III, IR; and Group IV, IR and LLLT. Groups III and
      IV received a single dose (30 Gy) of gamma radiation and underwent surgery 28
      days later. A noncritical sized bone defect (diameter 2.5 mm) was surgically
      created in all groups. Groups II and IV received three applications of
      postsurgical LLLT (GaAlAs, 808 nm, 100 mW, 0.028 cm(2), 3.57 W/cm(2), 20 sec, 2
      J,?71.4 J/cm(2)) on alternate days. Histomorphometry was assessed following
      digital image analysis. RESULTS: The samples were evaluated on days 7, 14, and 21
      after surgery; the IR protocol resulted in a significant reduction (p<0.018) in
      bone formation in Group III compared with Group I. Significant increases
      (p<0.006) in newly formed bone were noted in Group IV compared with Group III. No
      significant differences were observed between Group I and Group IV. CONCLUSIONS:
      LLLT increased the newly formed bone area during the initial phase of the tibiae
      repair process in rats exposed to IR.

PMID- 25372455
TI  - Laser lipolysis without suction: reality or myth?
AB  - BACKGROUND AND OBJECTIVE: Liposuction is one of the most frequently performed
      aesthetic surgical procedures. Laser- and ultrasound-based systems have become
      especially popular in recent years, including laser lipolysis, which has a number
      of advantages over classic liposuction. Some researchers contend that the
      aspiration step is not necessary. Herein, we report a case that highlights the
      negative consequences when the basic surgical rule of not leaving any necrotic
      tissue is not followed. MATERIALS AND METHODS: We report the case of a 50-year
      old man who presented with a 15 cm mass in the right lower quadrant, located
      immediately subcutaneously, passing the midline infraumbilically, tender to
      touch, and with beginnings of abscess formation, who underwent laser lipolysis.
      The subcutaneous necrotic fat was removed with a skin island en bloc. No
      postoperative complications occurred and the patient was problem free 6 months
      post-surgery. RESULTS: In the surgical literature, most studies on fat necrosis
      have focused on fat necrosis in the breast. Fat necrosis is usually a gradual
      process that is noticed by the patient or physician as a mass. Radiologically, it
      can imitate cancer, especially in breast tissue. Complications from fat necrosis
      are primarily linked to the amount of necrosis. Any amount of necrosis above the
      body's resorption capacity will lead the body into attempting self-limitation,
      with consequences to both the physical and psychological health of the patient.
      CONCLUSIONS: We believe that claiming that no aspiration is required after laser
      lipolysis, without the necessary studies, has no scientific basis.

PMID- 25372456
TI  - Disturbed spatial cognitive processing of body-related stimuli in a case of a
      lesion to the right fusiform gyrus.
AB  - The fusiform gyrus (FG) is well known as one of the main neural sites of human
      face and body processing. We report the case of a young male patient with
      epilepsy and a circumscribed lesion in the right FG who presented with isolated
      impairments in spatial cognitive processing of body-related stimuli. However, he
      did not show any clinical signs of prosopagnosia. In particular,
      handling/processing of body and face stimuli was impaired, when stimuli were
      presented in unconventional views and orientations, thus requiring additional
      spatial cognitive operations. In this case study, we discuss the patient's
      selective impairment from the view of current empirical and theoretical work on
      the segregation of functions in the FG. 

PMID- 25372457
TI  - Cyclen-based cationic lipids containing a pH-sensitive moiety as gene delivery
      vectors.
AB  - A series of novel cationic lipids based on 1,4,7,10-tetrazacyclododecane (cyclen)
      with the imidazole group as the pH-sensitive moiety and various aliphatic long
      chains were designed and synthesized. Cationic liposomes were prepared by mixing
      the lipids and the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
      (DOPE) in an appropriate molar ratio. The liposomes showed good stability and
      could condense plasmid DNA into nanosized particles (~100 to ~250 nm) with a
      positive zeta-potential (+10-25 mV). CCK-8-based cell viability assays showed a
      relatively lower cytotoxicity of the lipoplexes compared to commercially
      available lipofectamine 2000. Both enhanced green fluorescent protein and
      luciferase assays were carried out to investigate the in vitro transfection
      efficiency (TE) of the lipoplexes. Results showed that both the structures of the
      hydrophobic chain and the linking bond significantly affected the TE, and the
      linoleyl-containing lipoplex gave the best TE, which is comparable to
      lipofectamine 2000. The imidazole group was demonstrated to play an important
      role in the transfection, and the imidazole-absent analog gave dramatically lower
      TE. Furthermore, it was also found that Ca(2+) could largely enhance the TE of
      these lipids, and the optimized TE was about 5 times higher than lipofectamine
      2000. Flow cytometry demonstrates that the enhancement of TE by Ca(2+) was caused
      by the improvement of cellular uptake. These results suggest that the cyclen
      imidazole containing lipids might be promising non-viral gene delivery vectors. 

PMID- 25372458
TI  - Origin and expansion of the Yunnan Shoot Borer, Tomicus yunnanensis (coleoptera:
      scolytinae): a mixture of historical natural expansion and contemporary human
      mediated relocation.
AB  - The Yunnan shoot borer, Tomicus yunnanensis, is a recently-discovered, aggressive
      pest of the Yunnan pine stands in southwestern China. Despite many bionomics
      studies and massive controlling efforts, research on its population genetics is
      extremely limited. The present study, aimed at investigating the origin and
      dispersal of this important forestry pest, analyzed the population genetic
      structure and demographic history using a mitochondrial cox1 gene fragment. Our
      results showed that T. yunnanensis most likely originated from the Central-Yunnan
      Altiplano, and the divergence time analysis placed the origin approximately 0.72
      million-years ago. Host separation and specialization might have caused the
      speciation of T. yunnanensis. Genetic structure analyses identified two
      population groups, with six populations near the origin area forming one group
      and the remaining six populations from western and eastern Yunnan and
      southwestern Sichuan comprising the other. Divergence time analysis placed the
      split of the two groups at approximately 0.60 million-years ago, and haplotype
      phylogenetic tree, network, as well as migration rate suggested that populations
      of the latter group were established via a small number of individuals from the
      former one. Migration analysis also showed a certain degree of recent expansion
      from southwestern Sichuan to eastern Yunnan. Our findings implied that T.
      yunnanensis underwent both historical expansion and recent dispersal. The
      historical expansion may relate to the oscillation of regional climate due to
      glacial and interglacial periods in the Pleistocene, while human-mediated
      transportation of pine-wood material might have assisted the relocation and
      establishment of this pest in novel habitats. 

PMID- 25372460
TI  - Medicare Managed Care CAHPS(r): A Tool for Performance Improvement.
AB  - The Medicare+Choice (M+C) program, created by the 1997 Balanced Budget Act (BBA),
      expands Medicare's health insurance options to include a wider range of health
      plan options. In this article, we describe the Consumer Assessment of Health
      Plans Study (CAHPS(r)) survey and its use with beneficiaries receiving care
      through Medicare managed care (MMC) plans. We also discuss the implications of
      these efforts for future quality improvement efforts.

PMID- 25372461
TI  - Seasonal dynamics of Atlantic herring (Clupea harengus L.) populations spawning
      in the vicinity of marginal habitats.
AB  - Gillnet sampling and analyses of otolith shape, vertebral count and growth
      indicated the presence of three putative Atlantic herring (Clupea harengus L.)
      populations mixing together over the spawning season February-June inside and
      outside an inland brackish water lake (Landvikvannet) in southern Norway. Peak
      spawning of oceanic Norwegian spring spawners and coastal Skagerrak spring
      spawners occurred in March-April with small proportions of spawners entering the
      lake. In comparison, spawning of Landvik herring peaked in May-June with high
      proportions found inside the lake, which could be explained by local adaptations
      to the environmental conditions and seasonal changes of this marginal habitat.
      The 1.85 km(2) lake was characterized by oxygen depletion occurring between 2.5
      and 5 m depth between March and June. This was followed by changes in salinity
      from 1-70/00 in the 0-1 m surface layer to levels of 20-250/00 deeper than 10 m.
      In comparison, outside the 3 km long narrow channel connecting the lake with the
      neighboring fjord, no anoxic conditions were found. Here salinity in the surface
      layer increased over the season from 10 to 250/00, whereas deeper than 5 m it was
      stable at around 350/00. Temperature at 0-5 m depth increased significantly over
      the season in both habitats, from 7 to 14  degrees C outside and 5 to 17  degrees
      C inside the lake. Despite differences in peak spawning and utilization of the
      lake habitat between the three putative populations, there was an apparent
      temporal and spatial overlap in spawning stages suggesting potential
      interbreeding in accordance with the metapopulation concept.

PMID- 25372462
TI  - Overview.
AB  - This overview discusses articles published in this issue of the Health Care
      Financing Review, entitled "Access to Health Services for Vulnerable
      Populations." These articles focus on the following topics: access to Medicaid
      for pregnant women, access measures by health status, racial access questions,
      end stage renal disease (ESRD) patients, other special populations, and the
      effects of physician payment reform.

PMID- 25372459
TI  - Regulation of the orphan nuclear receptor Nr2f2 by the DFNA15 deafness gene
      Pou4f3.
AB  - Hair cells are the mechanotransducing cells of the inner ear that are essential
      for hearing and balance. POU4F3--a POU-domain transcription factor selectively
      expressed by these cells--has been shown to be essential for hair cell
      differentiation and survival in mice and its mutation in humans underlies late
      onset progressive hearing loss (DFNA15). The downstream targets of POU4F3 are
      required for hair cell differentiation and survival. We aimed to identify such
      targets in order to elucidate the molecular pathways involved in hair cell
      production and maintenance. The orphan thyroid nuclear receptor Nr2f2 was
      identified as a POU4F3 target using a subtractive hybridization strategy and EMSA
      analysis showed that POU4F3 binds to two sites in the Nr2f2 5' flanking region.
      These sites were shown to be required for POU4F3 activation as their mutation
      leads to a reduction in the response of an Nr2f2 5' flanking region reporter
      construct to POU4F3. Immunocytochemistry was carried out in the developing and
      adult inner ear in order to investigate the relevance of this interaction in
      hearing. NR2F2 expression in the postnatal mouse organ of Corti was shown to be
      detectable in all sensory epithelia examined and characterised. These data
      demonstrate that Nr2f2 is a direct target of POU4F3 in vitro and that this
      regulatory relationship may be relevant to hair cell development and survival.

PMID- 25372463
TI  - Accelerating the design of solar thermal fuel materials through high throughput
      simulations.
AB  - Solar thermal fuels (STF) store the energy of sunlight, which can then be
      released later in the form of heat, offering an emission-free and renewable
      solution for both solar energy conversion and storage. However, this approach is
      currently limited by the lack of low-cost materials with high energy density and
      high stability. In this Letter, we present an ab initio high-throughput
      computational approach to accelerate the design process and allow for searches
      over a broad class of materials. The high-throughput screening platform we have
      developed can run through large numbers of molecules composed of earth-abundant
      elements and identifies possible metastable structures of a given material.
      Corresponding isomerization enthalpies associated with the metastable structures
      are then computed. Using this high-throughput simulation approach, we have
      discovered molecular structures with high isomerization enthalpies that have the
      potential to be new candidates for high-energy density STF. We have also
      discovered physical principles to guide further STF materials design through
      structural analysis. More broadly, our results illustrate the potential of using
      high-throughput ab initio simulations to design materials that undergo targeted
      structural transitions. 

PMID- 25372464
TI  - Consequences of missed opportunities for HIV testing during pregnancy and delayed
      diagnosis for Mexican women, children and male partners.
AB  - INTRODUCTION: HIV testing during pregnancy permits prevention of vertical (mother
      to-child) transmission and provides an opportunity for women living with HIV to
      access treatment for their own health. In 2001, Mexico's National HIV Action Plan
      committed to universal offer of HIV testing to pregnant women, but in 2011, only
      45.6% of women who attended antenatal care (ANC) were tested for HIV. The study
      objective was to document the consequences of missed opportunities for HIV
      testing and counseling during pregnancy and late HIV diagnosis for Mexican women
      living with HIV and their families. METHODS: Semi-structured-interviews with 55
      women living with HIV who had had a pregnancy since 2001 were completed between
      2009 and 2011. Interviews were analyzed thematically using a priori and inductive
      codes. RESULTS: Consistent with national statistics, less than half of the women
      living with HIV (42%) were offered HIV testing and counseling during ANC. When
      not diagnosed during ANC, women had multiple contacts with the health-care system
      due to their own and other family members' AIDS-related complications before
      being diagnosed. Missed opportunities for HIV testing and counseling during
      antenatal care and health-care providers failure to recognize AIDS-related
      complications resulted in pediatric HIV infections, AIDS-related deaths of
      children and male partners, and HIV disease progression among women and other
      family members. In contrast, HIV diagnosis permitted timely access to
      interventions to prevent vertical HIV transmission and long-term care and
      treatment for women living with HIV. CONCLUSIONS: Omissions of the offer of HIV
      testing and counseling in ANC and health-care providers' failure to recognize
      AIDS-related complications had negative health, economic and emotional
      consequences. Scaling-up provider-initiated HIV testing and counseling within and
      beyond antenatal care and pre-service and in-service trainings on HIV and AIDS
      for health-care providers can hasten timely HIV diagnosis and contribute to
      improved individual and public health in Mexico.

PMID- 25372465
TI  - The trophoblast model of cancer.
AB  - John Beard, the British embryologist and histologist, first proposed his
      trophoblast model of cancer in 1902. The model has subsequently been expanded by
      Kelley, and in current times, Gonzalez and Isaacs. The trophoblast model of
      cancer can be stated as a specified, scientifically testable model, including its
      core predictions that 1) adult stem cells are ectopic trophoblasts that have
      migrated to other tissues early in embryogenesis; 2) pancreatic enzymes are the
      key signal that converts the trophoblast into the stable placenta; 3) cancer
      arises from trophoblasts that have escaped regulatory control; and 4) pancreatic
      enzymes can be used to treat cancer. The author reviewed the literature on the
      trophoblast model of cancer and the use of pancreatic enzymes for the treatment
      of cancer and organized its key tenets into a set of specified scientific
      hypotheses. The trophoblast model of cancer can be stated as a set of 11 core
      predictions and 3 adjunctive or nonessential components. The trophoblast model of
      cancer is a detailed, testable model that should be investigated within an
      overlapping set of fields including oncology, histology, physiology, molecular
      biology, and embryology. 

PMID- 25372466
TI  - Hospitalizations for Injury Among Medicaid Children: California, 1992.
AB  - Little is known about the incidence and cost of injuries for Medicaid children.
      This article provides data on hospital utilization and payments for injuries
      among Medicaid children, using the Health Care Financing Administration's (HCFA)
      State Medicaid Research Files. During 1992, there were nearly 17,000 injury
      hospitalizations for California's Medicaid children (758 per 100,000 enrollees),
      representing over $93 million in program payments. The most frequent injury
      hospitalizations were fractures and dislocations. Disabled children and 18- to 20
      year-old males experienced the highest hospital utilization rates. These findings
      will assist Medicaid policymakers in targeting prevention efforts to reduce
      incidence and program payments for children's injuries.

PMID- 25372467
TI  - Health Care Indicators.
AB  - This regular feature of the journal includes a discussion of each of the
      following four topics community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25372468
TI  - An elevated peripheral blood lymphocyte-to-monocyte ratio predicts favorable
      response and prognosis in locally advanced breast cancer following neoadjuvant
      chemotherapy.
AB  - PURPOSE: Neoadjuvant chemotherapy (NCT) is a standard treatment option for
      locally advanced breast cancer. However, the lack of an efficient method to
      predict treatment response and patient prognosis hampers the clinical evaluation
      of patient eligibility for NCT. An elevated lymphocyte-to-monocyte ratio (LMR)
      has been reported to be associated with a favorable prognosis for certain
      hematologic malignancies and for nasopharyngeal carcinoma; however, this
      association has not been investigated in breast cancer. The purpose of this study
      was to evaluate whether pre-NCT LMR analysis could predict the prognosis of
      patients with locally advanced breast cancer. METHODS: A retrospective cohort of
      542 locally advanced breast cancer patients (T3/T4 and/or N2/N3 disease)
      receiving NCT followed by radical surgery was recruited between May 2002 and
      August 2011 at the Fudan University Shanghai Cancer Center. Counts for pre-NCT
      peripheral absolute lymphocytes and monocytes were obtained and used to calculate
      the LMR. RESULTS: Univariate and multivariate analysis revealed that higher LMR
      levels (>=4.25) were significantly associated with favorable DFS (P = 0.009 and P
      = 0.011, respectively). Additionally, univariate analysis revealed that a higher
      lymphocyte count (>=1.5*109/L) showed borderline significance for improved DFS (P
      = 0.054), while a lower monocyte count (<0.4*109/L) was associated with a
      significantly better DFS (P = 0.010). CONCLUSIONS: An elevated pre-NCT peripheral
      LMR level was a significantly favorable factor for locally advanced breast cancer
      patient prognosis. This easily obtained variable may serve as a valuable marker
      to predict the outcomes of locally advanced breast cancer.

PMID- 25372469
TI  - The expansion of the pulmonary rib cage during breath stacking is influenced by
      age in obese women.
AB  - OBJECTIVE: To analyze in obese women the acute effects of the breath stacking
      technique on thoraco-abdominal expansion. DESIGN AND METHODS: Nineteen obese
      women (BMI >= 30 kg/m(2)) were evaluated by anthropometry, spirometry and maximal
      respiratory muscle pressures and successively analyzed by Opto-Electronic
      Plethysmography and a Wright respirometer during quiet breathing and breath
      stacking maneuvers and compared with a group of 15 normal-weighted healthy women.
      The acute effects of the maneuvers were assessed in terms of total and
      compartmental chest wall volumes at baseline, end of the breath stacking maneuver
      and after the maneuver. Obese subjects were successively classified into two
      groups, accordingly to the response during the maneuver, group 1 = prevalent rib
      cage or group 2 = abdominal expansion. RESULTS: Age was significantly lower in
      group 1 than group 2. When considering the two obese groups, FEV1 was lower and
      minute ventilation was higher only in group 2 compared to controls group. During
      breath stacking, inspiratory capacity was significant differences in obese
      subjects with a smaller expansion of the pulmonary rib cage and a greater
      expansion of the abdomen compared to controls and also between groups 1 and 2. A
      significant inverse linear relationship was found between age and inspiratory
      capacity of the pulmonary rib cage but not of the abdomen. CONCLUSIONS: In obese
      women the maximal expansion of the rib cage and abdomen is influenced by age and
      breath stacking maneuver could be a possible therapy for preventing respiratory
      complications.

PMID- 25372470
TI  - A tyrosine-rich cell surface protein in the diatom Amphora coffeaeformis
      identified through transcriptome analysis and genetic transformation.
AB  - Diatoms are single-celled eukaryotic microalgae that are ubiquitously found in
      almost all aquatic ecosystems, and are characterized by their intricately
      structured SiO2 (silica)-based cell walls. Diatoms with a benthic life style are
      capable of attaching to any natural or man-made submerged surface, thus
      contributing substantially to both microbial biofilm communities and economic
      losses through biofouling. Surface attachment of diatoms is mediated by a
      carbohydrate- and protein- based glue, yet no protein involved in diatom
      underwater adhesion has been identified so far. In the present work, we have
      generated a normalized transcriptome database from the model adhesion diatom
      Amphora coffeaeformis. Using an unconventional bioinformatics analysis we have
      identified five proteins that exhibit unique amino acid sequences resembling the
      amino acid composition of the tyrosine-rich adhesion proteins from mussel
      footpads. Establishing the first method for the molecular genetic transformation
      of A. coffeaeformis has enabled investigations into the function of one of these
      proteins, AC3362, through expression as YFP fusion protein. Biochemical analysis
      and imaging by fluorescence microscopy revealed that AC3362 is not involved in
      adhesion, but rather plays a role in biosynthesis and/or structural stability of
      the cell wall. The methods established in the present study have paved the way
      for further molecular studies on the mechanisms of underwater adhesion and
      biological silica formation in the diatom A. coffeaeformis. 

PMID- 25372471
TI  - Antiplatelet effects of Rhus verniciflua stokes heartwood and its active
      constituents--fisetin, butein, and sulfuretin--in rats.
AB  - Rhus verniciflua stokes (RVS) is known to promote blood circulation by preventing
      blood stasis, although the active ingredients and the underlying mechanism are
      unclear. Platelets are the primary cells that regulate circulation and contribute
      to the development of diverse cardiovascular diseases by aggregation and
      thrombosis. The study assessed the antiplatelet activity of RVS and sought to
      identify the active constituents. Pretreatment of washed platelets with RVS
      heartwood extract blunted the aggregatory response of platelets to collagen. In
      the subfractions, fisetin, butein, and sulfuretin were identified as effective
      inhibitors of platelet aggregation by collagen, thrombin, and adenosine-5'
      diphosphate. Antiplatelet activities of all three compounds were concentration
      dependent, and fisetin had longer in vitro duration of action compared with
      butein or sulfuretin. Extracellular signal-regulated kinase (ERK) mitogen
      activated protein kinase activation by collagen was prevented by fisetin, whereas
      butein and sulfuretin failed to inhibit ERK and p38 activation was not affected
      by any of the compounds. Rats orally administered 100 mg/(kg.day(-1)) fisetin for
      7 days were resistant to arterial thrombosis, although total extract of RVS
      heartwood exhibited little effect at a dose of 1000 mg/(kg.day(-1)). RVS
      heartwood may have cardiovascular protective activity by inhibiting platelet
      aggregation. The active constituents are fisetin, butein, and sulfuretin, and
      fisetin is orally effective against thrombosis.

PMID- 25372472
TI  - Electrophysiological studies and radiofrequency ablations in children and
      adolescents with arrhythmia.
AB  - BACKGROUND: Radiofrequency ablation is the standard non-pharmacological treatment
      for arrhythmias in pediatric patients. However, arrhythmias and their associated
      causes have particular features in this population. OBJECTIVE: To analyze the
      epidemiological characteristics and findings of electrophysiological diagnostic
      studies and radiofrequency ablations in pediatric patients referred to the
      Electrophysiology Unit at Instituto de Cardiologia do Rio Grande do Sul, in order
      to characterize the particularities of this population. METHODS: Cross-sectional
      study with 330 electrophysiological procedures performed in patients aged less
      than 20 years between June 1997 and August 2013. RESULTS: In total, 330
      procedures (9.6% of the overall procedures) were performed in patients aged less
      than 20 years (14.33 +/- 3.25 years, age range 3 months to 19 years), 201 of
      which were males (60.9%). A total of 108 (32.7%) electrophysiological diagnostic
      studies were performed and of these, 48.1% showed abnormal findings. Overall, 219
      radiofrequency ablations were performed (66.3%) with a success rate of 84.8%. The
      presence of an accessory pathway was the most prevalent finding, occurring in 158
      cases (72.1%), followed by atrioventricular nodal reentrant tachycardia (16.8%),
      typical atrial flutter (3.1%) and extrasystoles originating from the right
      ventricular outflow tract (2.7%). Three patients developed complications during
      ablation (1.4%). Among congenital heart diseases, which occurred in 51 (15.4%)
      patients, atrial sept defect was the most frequent (27.4%), followed by
      ventricular sept defect (25.4%) and Ebstein's anomaly (17.6%). CONCLUSION:
      Electrophysiological study and radiofrequency ablation are effective tools for
      diagnosis and treatment of arrhythmias in the pediatric population.

PMID- 25372475
TI  - Efficient merging of copper and photoredox catalysis for the asymmetric cross
      dehydrogenative-coupling of alkynes and tetrahydroisoquinolines.
AB  - A highly efficient catalytic asymmetric alkynylation of prochiral CH2 groups in
      tetrahydroisoquinoline was developed using copper catalyzed cross-dehydrogenative
      coupling of sp(3) and sp C-H bonds with the assistance of a photocatalyst and
      visible light. 

PMID- 25372474
TI  - Use of short-term circulatory support as a bridge in pediatric heart
      transplantation.
AB  - BACKGROUND: Heart transplantation is considered the gold standard therapy for the
      advanced heart failure, but donor shortage, especially in pediatric patients, is
      the main limitation for this procedure, so most sick patients die while waiting
      for the procedure. OBJECTIVE: To evaluate the use of short-term circulatory
      support as a bridge to transplantation in end-stage cardiomyopathy. METHODS:
      Retrospective clinical study. Between January 2011 and December 2013, 40 patients
      with cardiomyopathy were admitted in our Pediatric Intensive Care Unit, with a
      mean age of 4.5 years. Twenty patients evolved during hospitalization with
      clinical deterioration and were classified as Intermacs 1 and 2. One patient died
      within 24 hours and 19 could be stabilized and were listed. They were divided
      into 2 groups: A, clinical support alone and B, implantation of short-term
      circulatory support as bridge to transplantation additionally to clinical
      therapy. RESULTS: We used short-term mechanical circulatory support as a bridge
      to transplantation in 9. In group A (n=10), eight died waiting and 2 patients
      (20%) were transplanted, but none was discharged. In group B (n=9), 6 patients
      (66.7%) were transplanted and three were discharged.The mean support time was
      21,8 days (6 to 984 h). The mean transplant waiting list time was 33,8 days.
      Renal failure and sepsis were the main complication and cause of death in group A
      while neurologic complications were more prevalent en group B. CONCLUSION:
      Mechanical circulatory support increases survival on the pediatric heart
      transplantation waiting list in patients classified as Intermacs 1 and 2.

PMID- 25372478
TI  - Containing health costs in a consumer-based model.
AB  - The assumption that consumer choice cannot be used to achieve cost control in
      health care is invalid. It does not do so today because the tax treatment of
      health care leads to perverse consumer incentives that encourage cost escalation.
      By reforming the tax treatment of insurance and out-of-pocket medical costs, it
      is possible to design an efficient and universal system in which consumer choice
      is a powerful restraint on cost.

PMID- 25372480
TI  - Synthetic analogues of the marine bisindole deoxytopsentin: potent selective
      inhibitors of MRSA pyruvate kinase.
AB  - As part of an ongoing study to elucidate the SAR of bisindole alkaloid inhibitors
      against the evolutionary conserved MRSA pyruvate kinase (PK), we present here the
      synthesis and biological activity of six dihalogenated analogues of the naturally
      occurring sponge metabolite deoxytopsentin, including the naturally occurring
      dibromodeoxytopsentin. The most active compounds displayed potent low nanomolar
      inhibitory activity against MRSA PK with concomitant significant selectivity for
      MRSA PK over human PK orthologues. Computational studies suggest that these
      potent MRSA PK inhibitors occupy a region of the small interface of the enzyme
      tetramer where amino acid sequence divergence from common human PK orthologues
      may contribute to the observed selectivity. 

PMID- 25372479
TI  - A systematic review of individual and contextual factors affecting ART
      initiation, adherence, and retention for HIV-infected pregnant and postpartum
      women.
AB  - BACKGROUND: Despite progress reducing maternal mortality, HIV-related maternal
      deaths remain high, accounting, for example, for up to 24 percent of all
      pregnancy-related deaths in sub-Saharan Africa. Antiretroviral therapy (ART) is
      effective in improving outcomes among HIV-infected pregnant and postpartum women,
      yet rates of initiation, adherence, and retention remain low. This systematic
      literature review synthesized evidence about individual and contextual factors
      affecting ART use among HIV-infected pregnant and postpartum women. METHODS:
      Searches were conducted for studies addressing the population (HIV-infected
      pregnant and postpartum women), intervention (ART), and outcomes of interest
      (initiation, adherence, and retention). Quantitative and qualitative studies
      published in English since January 2008 were included. Individual and contextual
      enablers and barriers to ART use were extracted and organized thematically within
      a framework of individual, interpersonal, community, and structural categories.
      RESULTS: Thirty-four studies were included in the review. Individual-level
      factors included both those within and outside a woman's awareness and control
      (e.g., commitment to child's health or age). Individual-level barriers included
      poor understanding of HIV, ART, and prevention of mother-to-child transmission,
      and difficulty managing practical demands of ART. At an interpersonal level,
      disclosure to a spouse and spousal involvement in treatment were associated with
      improved initiation, adherence, and retention. Fear of negative consequences was
      a barrier to disclosure. At a community level, stigma was a major barrier. Key
      structural barriers and enablers were related to health system use and
      engagement, including access to services and health worker attitudes.
      CONCLUSIONS: To be successful, programs seeking to expand access to and continued
      use of ART by integrating maternal health and HIV services must identify and
      address the relevant barriers and enablers in their own context that are
      described in this review. Further research on this population, including those
      who drop out of or never access health services, is needed to inform effective
      implementation.

PMID- 25372482
TI  - Risk Adjustment for Dually Eligible Beneficiaries Using Long-Term Care.
AB  - This study explores use of the principal inpatient diagnostic cost groups
      (PIPDCG) and hierarchical coexisting conditions (HCC) risk-adjustment
      methodologies for a population of dually eligible beneficiaries receiving chronic
      long-term care (LTC). Measures of individual predictive accuracy for this
      population compared with the total Medicare population were similar for the
      PIPDCG models but somewhat smaller for the HCC models. Incorporating measures of
      functional status increased the R2 values by only a small amount for Medicare
      expenditures but by a somewhat larger amount for total expenditures. Addition of
      other variables, especially placement, further improved the predictive power.

PMID- 25372484
TI  - Conventional health insurance: A decade later.
AB  - In this article, the 1987 conventional health plans are examined and 1987 group
      health insurance is compared with that of 1977. The source of information for
      1987 is the national survey of 771 private and public employers conducted by the
      Health Insurance Association of America. Data for 1977 are from the National
      Medical Care Expenditures Survey. Findings show that conventional health plans'
      share of the group market declined from 95 to 73 percent during the decade; the
      majority of Americans covered by conventional group insurance are now enrolled in
      a plan that self-insures; prospective utilization review grew dramatically after
      1984; and patient cost sharing increased, but not as significantly as
      conventional wisdom holds.

PMID- 25372483
TI  - Efficacy of standard and intensive statin treatment for the secondary prevention
      of cardiovascular and cerebrovascular events in diabetes patients: a meta
      analysis.
AB  - AIMS: To estimate the efficacy of standard and intensive statin treatment in the
      secondary prevention of major cardiovascular and cerebrovascular events in
      diabetes patients. METHODS: A systematic search was conducted in Medline over the
      years 1990 to September 2013. Randomized, double-blind, clinical trials comparing
      a standard-dose statin with placebo or a standard-dose statin with an intensive
      dose statin for the secondary prevention of cardiovascular and cerebrovascular
      events in diabetes patients were selected. Trial and patient characteristics were
      extracted independently by two researchers. The combined effect on the composite
      primary endpoint was measured with a fixed-effect model. Potential publication
      bias was examined with a funnel plot. RESULTS: Five trials were included in the
      analysis comparing standard-dose statins with placebo with a total of 4 351
      participants. Four trials were included for comparing standard-dose with
      intensive-dose statins, including 4 805 participants. Compared with placebo,
      standard-dose statin treatment resulted in a significant relative risk (RR)
      reduction of 15% in the occurrence of any major cardiovascular or cerebrovascular
      event (RR 0.85, 95% CI 0.79-0.91). Compared with standard-dose statin treatment,
      intensive-dose statin treatment resulted in an additional 9% relative risk
      reduction (RR 0.91, 95% CI 0.84-0.98). CONCLUSION: Treatment with standard-dose
      statins to prevent cardiovascular or cerebrovascular events in diabetes patients
      with manifest cardiovascular disease results in an estimated 15% relative risk
      reduction and intensive-dose statin treatment adds 9%. If proven cost-effective,
      more intensive statin treatment should be recommended for diabetes patients at
      high cardiovascular risk.

PMID- 25372485
TI  - Consequences of the trans-Atlantic slave trade on medicinal plant selection:
      plant use for cultural bound syndromes affecting children in Suriname and Western
      Africa.
AB  - Folk perceptions of health and illness include cultural bound syndromes (CBS),
      ailments generally confined to certain cultural groups or geographic regions and
      often treated with medicinal plants. Our aim was to compare definitions and plant
      use for CBS regarding child health in the context of the largest migration in
      recent human history: the trans-Atlantic slave trade. We compared definitions of
      four CBS (walk early, evil eye, atita and fontanels) and associated plant use
      among three Afro-Surinamese populations and their African ancestor groups in
      Ghana, Benin and Gabon. We expected plant use to be similar on species level, and
      assumed the majority to be weedy or domesticated species, as these occur on both
      continents and were probably recognized by enslaved Africans. Data were obtained
      by identifying plants mentioned during interviews with local women from the six
      different populations. To analyse differences and similarities in plant use we
      used Detrended Component Analysis (DCA) and a Wald Chi-square test. Definitions
      of the four cultural bound syndromes were roughly the same on both continents. In
      total, 324 plant species were used. There was little overlap between Suriname and
      Africa: 15 species were used on two continents, of which seven species were used
      for the same CBS. Correspondence on family level was much higher. Surinamese
      populations used significantly more weedy species than Africans, but equal
      percentages of domesticated plants. Our data indicate that Afro-Surinamers have
      searched for similar plants to treat their CBS as they remembered from Africa. In
      some cases, they have found the same species, but they had to reinvent the
      largest part of their herbal pharmacopeia to treat their CBS using known plant
      families or trying out new species. Ideas on health and illness appear to be more
      resilient than the use of plants to treat them. 

PMID- 25372486
TI  - Modulation of K(Ca)3.1 channels by eicosanoids, omega-3 fatty acids, and
      molecular determinants.
AB  - BACKGROUND: Cytochrome P450- and omega-hydrolase products (epoxyeicosatrienoic
      acids (EETs), hydroxyeicosatetraeonic acid (20-HETE)), natural omega-3 fatty
      acids (omega3), and pentacyclic triterpenes have been proposed to contribute to a
      wide range of vaso-protective and anti-fibrotic/anti-cancer signaling pathways
      including the modulation of membrane ion channels. Here we studied the modulation
      of intermediate-conductance Ca(2+)/calmodulin-regulated K(+) channels (K(Ca)3.1)
      by EETs, 20-HETE, omega3, and pentacyclic triterpenes and the structural
      requirements of these fatty acids to exert channel blockade.
      METHODOLOGY/PRINCIPAL FINDINGS: We studied modulation of cloned human hK(Ca)3.1
      and the mutant hK(Ca)3.1(V275A) in HEK-293 cells, of rK(Ca)3.1 in aortic
      endothelial cells, and of mK(Ca)3.1 in 3T3-fibroblasts by inside-out and whole
      cell patch-clamp experiments, respectively. In inside-out patches, Ca(2+)
      activated hK(Ca)3.1 were inhibited by the omega3, DHA and alpha-LA, and the
      omega6, AA, in the lower umolar range and with similar potencies. 5,6-EET, 8,9
      EET, 5,6-DiHETE, and saturated arachidic acid, had no appreciable effects. In
      contrast, 14,15-EET, its stable derivative, 14,15-EEZE, and 20-HETE produced
      channel inhibition. 11,12-EET displayed less inhibitory activity. The
      K(Ca)3.1(V275A) mutant channel was insensitive to any of the blocking EETs. Non
      blocking 5,6-EET antagonized the inhibition caused by AA and augmented cloned
      hK(Ca)3.1 and rK(Ca)3.1 whole-cell currents. Pentacyclic triterpenes did not
      modulate K(Ca)3.1 currents. CONCLUSIONS/SIGNIFICANCE: Inhibition of K(Ca)3.1 by
      EETs (14,15-EET), 20-HETE, and omega3 critically depended on the presence of
      electron double bonds and hydrophobicity within the 10 carbons preceding the
      carboxyl-head of the molecules. From the physiological perspective, metabolism of
      AA to non-blocking 5,6,- and 8,9-EET may cause AA-de-blockade and contribute to
      cellular signal transduction processes influenced by these fatty acids.

PMID- 25372487
TI  - [Pt(O,O'-acac)(gamma-acac)(DMS)] alters SH-SY5Y cell migration and invasion by
      the inhibition of Na+/H+ exchanger isoform 1 occurring through a PKC
      epsilon/ERK/mTOR Pathway.
AB  - We previously showed that [Pt(O,O'-acac)(gamma-acac)(DMS)] ([Pt(acac)2(DMS)])
      exerted substantial cytotoxic effects in SH-SY5Y neuroblastoma cells, and
      decreased metalloproteases (MMPs) production and cells migration in MCF-7 breast
      cancer cells. The ubiquitously distributed sodium-hydrogen antiporter 1 (NHE1) is
      involved in motility and invasion of many solid tumours. The present study
      focuses on the effects of [Pt(acac)2(DMS)] in SH-SY5Y cell migration and also on
      the possibility that NHE1 may be involved in such effect. After sublethal
      [Pt(acac)2(DMS)] treatment cell migration was examined by wounding assay and cell
      invasion by transwell assay. NHE1 activity was measured in BCECF-loaded SH-SY5Y
      as the rate of Na+-dependent intracellular pH recovery in response to an acute
      acid pulse. Gelatin zymography for MMP-2/9 activities, Western blottings of MMPs,
      MAPKs, mTOR, S6 and PKCs and small interfering RNAs to PKC-epsilon/-delta mRNA
      were performed. Sublethal concentrations of [Pt(acac)2(DMS)] decreases NHE1
      activity, inhibits cell migration and invasion and decreases expression and
      activity of MMP-2 and -9. [Pt(acac)2(DMS)] administered to SH-SY5Y cells provokes
      the increment of ROS, generated by NADPH oxidase, responsible for the PKC-epsilon
      and PKC-delta activation. Whilst PKC-delta activates p38/MAPK, responsible for
      the inhibition of MMP-2 and -9 secretion, PKC-epsilon activates a pathway made of
      ERK1/2, mTOR and S6K responsible for the inhibition of NHE1 activity and cell
      migration. In conclusion, we have shown a drastic impairment in tumour cell
      metastatization in response to inhibition of NHE1 and MMPs activities by
      [Pt(acac)2(DMS)] occurring through a novel mechanism mediated by PKC-delta/
      epsilon activation.

PMID- 25372488
TI  - Functional aspects of the EGF-induced MAP kinase cascade: a complex self
      organizing system approach.
AB  - The EGF-induced MAP kinase cascade is one of the most important and best
      characterized networks in intracellular signalling. It has a vital role in the
      development and maturation of living organisms. However, when deregulated, it is
      involved in the onset of a number of diseases. Based on a computational model
      describing a "surface" and an "internalized" parallel route, we use systems
      biology techniques to characterize aspects of the network's functional
      organization. We examine the re-organization of protein groups from low to high
      external stimulation, define functional groups of proteins within the network,
      determine the parameter best encoding for input intensity and predict the effect
      of protein removal to the system's output response. Extensive functional re
      organization of proteins is observed in the lower end of stimulus concentrations.
      As we move to higher concentrations the variability is less pronounced. 6
      functional groups have emerged from a consensus clustering approach, reflecting
      different dynamical aspects of the network. Mutual information investigation
      revealed that the maximum activation rate of the two output proteins best encodes
      for stimulus intensity. Removal of each protein of the network resulted in a
      range of graded effects, from complete silencing to intense activation. Our
      results provide a new "vista" of the EGF-induced MAP kinase cascade, from the
      perspective of complex self-organizing systems. Functional grouping of the
      proteins reveals an organizational scheme contrasting the current understanding
      of modular topology. The six identified groups may provide the means to
      experimentally follow the dynamics of this complex network. Also, the
      vulnerability analysis approach may be used for the development of novel
      therapeutic targets in the context of personalized medicine. 

PMID- 25372489
TI  - Survival of skin graft between transgenic cloned dogs and non-transgenic cloned
      dogs.
AB  - Whereas it has been assumed that genetically modified tissues or cells derived
      from somatic cell nuclear transfer (SCNT) should be accepted by a host of the
      same species, their immune compatibility has not been extensively explored. To
      identify acceptance of SCNT-derived cells or tissues, skin grafts were performed
      between cloned dogs that were identical except for their mitochondrial DNA
      (mtDNA) haplotypes and foreign gene. We showed here that differences in mtDNA
      haplotypes and genetic modification did not elicit immune responses in these
      dogs: 1) skin tissues from genetically-modified cloned dogs were successfully
      transplanted into genetically-modified cloned dogs with different mtDNA haplotype
      under three successive grafts over 63 days; and 2) non-transgenic cloned tissues
      were accepted into transgenic cloned syngeneic recipients with different mtDNA
      haplotypes and vice versa under two successive grafts over 63 days. In addition,
      expression of the inserted gene was maintained, being functional without
      eliciting graft rejection. In conclusion, these results show that transplanting
      genetically-modified tissues into normal, syngeneic or genetically-modified
      recipient dogs with different mtDNA haplotypes do not elicit skin graft rejection
      or affect expression of the inserted gene. Therefore, therapeutically valuable
      tissue derived from SCNT with genetic modification might be used safely in
      clinical applications for patients with diseased tissues. 

PMID- 25372491
TI  - Stability of Disability Among PACE Enrollees: Financial and Programmatic
      Implications.
AB  - This article examines the experience of the first 11 Program of All-inclusive
      Care for the Elderly (PACE) programs. It investigates changes in functional
      status of participants in relation to length of enrollment in the program and
      individual risk characteristics. Our findings indicate that mature programs
      experience stable disability mix over time, supporting the rationale for the
      current PACE payment method. However, significant differences exist between
      programs, suggesting that payment rates could be more program specific. Analysis
      of the effect of patient characteristics at admission on the likelihood of
      improvement in functional status identified areas for quality improvement. The
      implications of this study have increasing importance in light of the expected
      expansion of PACE to approximately 100 sites by the year 2000.

PMID- 25372490
TI  - Energy balance related behaviour: personal, home- and friend-related factors
      among schoolchildren in Europe studied in the ENERGY-project.
AB  - OBJECTIVE: To design interventions that target energy balance-related behaviours,
      knowledge of primary schoolchildren's perceptions regarding soft drink intake,
      fruit juice intake, breakfast consumption, TV viewing and physical activity (PA)
      is essential. The current study describes personal beliefs and attitudes, home-
      and friend-related variables regarding these behaviours across Europe. DESIGN:
      Cross-sectional study in which personal, family and friend -related variables
      were assessed by validated questionnaires, and dichotomized as favourable versus
      unfavourable answers. Logistic regression analyses were conducted to estimate
      proportions of children giving unfavourable answers and test between-country
      differences. SETTING: A survey in eight European countries. SUBJECTS: A total of
      7903 10-12 year old primary schoolchildren. RESULTS: A majority of the children
      reported unfavourable attitudes, preferences and subjective norms regarding soft
      drink, fruit juice intake and TV viewing accompanied with high availability and
      accessibility at home. Few children reported unfavourable attitudes and
      preferences regarding breakfast consumption and PA. Many children reported
      unfavourable health beliefs regarding breakfast consumption and TV viewing.
      Substantial differences between countries were observed, especially for variables
      regarding soft drink intake, breakfast consumption and TV viewing. CONCLUSION:
      The surveyed children demonstrated favourable attitudes to some healthy
      behaviours (PA, breakfast intake) as well as to some unhealthy behaviours (soft
      drink consumption, TV viewing). Additionally, many children across Europe have
      personal beliefs and are exposed to social environments that are not supportive
      to engagement in healthy behaviours. Moreover, the large differences in personal,
      family and friend-related variables across Europe argue for implementing
      different strategies in the different European countries.

PMID- 25372493
TI  - Health Care Quality Reporting: Changes and Challenges.

PMID- 25372492
TI  - Influence of Trichobilharzia regenti (Digenea: Schistosomatidae) on the defence
      activity of Radix lagotis (Lymnaeidae) Haemocytes.
AB  - Radix lagotis is an intermediate snail host of the nasal bird schistosome
      Trichobilharzia regenti. Changes in defence responses in infected snails that
      might be related to host-parasite compatibility are not known. This study
      therefore aimed to characterize R. lagotis haemocyte defence mechanisms and
      determine the extent to which they are modulated by T. regenti. Histological
      observations of R. lagotis infected with T. regenti revealed that early phases of
      infection were accompanied by haemocyte accumulation around the developing larvae
      2-36 h post exposure (p.e.) to the parasite. At later time points, 44-92 h p.e.,
      no haemocytes were observed around T. regenti. Additionally, microtubular
      aggregates likely corresponding to phagocytosed ciliary plates of T. regenti
      miracidia were observed within haemocytes by use of transmission electron
      microscopy. When the infection was in the patent phase, haemocyte phagocytic
      activity and hydrogen peroxide production were significantly reduced in infected
      R. lagotis when compared to uninfected counterparts, whereas haemocyte abundance
      increased in infected snails. At a molecular level, protein kinase C (PKC) and
      extracellular-signal regulated kinase (ERK) were found to play an important role
      in regulating these defence reactions in R. lagotis. Moreover, haemocytes from
      snails with patent infection displayed lower PKC and ERK activity in cell
      adhesion assays when compared to those from uninfected snails, which may
      therefore be related to the reduced defence activities of these cells. These data
      provide the first integrated insight into the immunobiology of R. lagotis and
      demonstrate modulation of haemocyte-mediated responses in patent T. regenti
      infected snails. Given that immunomodulation occurs during patency, interference
      of snail-host defence by T. regenti might be important for the sustained
      production and/or release of infective cercariae. 

PMID- 25372494
TI  - Computational studies on the binding mechanism between triazolone inhibitors and
      Chk1 by molecular docking and molecular dynamics.
AB  - Chk1, a serine/threonine protein kinase that participates in transducing DNA
      damage signals, is an attractive target due to its involvement in tumor
      initiation and progression. As a novel Chk1 inhibitor, the triazolone's
      bioactivity mechanism is not clear. In this study, we carried out an integrated
      computational study that combines molecular docking, molecular dynamics (MD)
      simulations, and binding free energy calculations to identify the key factors
      necessary for the bioactivities. With the aim of discerning the structural
      features that affect the inhibitory activity of triazolones, MK-8776, a Chk1
      inhibitor that reached the clinical stage, was also used as a reference for
      simulations. A comparative analysis of the triazolone inhibitors at the molecular
      level offers valuable insight into the structural and energetic properties. A
      general feature is that all the studied inhibitors bind in the pocket
      characterized by residues Leu14, Val22, Ala35, Glu84, Tyr85, Cys86, and Leu136 of
      Chk1. Moreover, introducing hydrophobic groups into triazolone inhibitors is
      favorable for binding to Chk1, which is corroborated by residue Leu136 with a
      relatively large difference in the contribution between MK-8776 and five
      triazolones to the total binding free energies. A hydrogen bond between the polar
      hydrogen atoms at R1 and Cys86 can facilitate proper placement of the inhibitor
      in the binding pocket of Chk1 that favors binding. However, the introduction of
      hydrophilic groups into the R2 position diminishes binding affinity. The
      information provided by this research is of benefit for further rational design
      of novel promising inhibitors of Chk1. 

PMID- 25372496
TI  - Provider Opt-Out Under Medicare Private Contracting.
AB  - The 1997 Balanced Budget Act (BBA) permits private contracting for care between
      Medicare beneficiaries and providers who have opted out of Medicare. This article
      examines the number and characteristics of providers who have opted-out, their
      role in the provision of Part B services, and their impact on beneficiary access
      from 1998 to 2002. Opt-out providers differ from providers remaining in Medicare
      with respect to specialty, practice characteristics, and Medicare Program
      activity. Very few providers found opting-out attractive and the departure of
      this small group of providers appears not to have created access problems for
      beneficiaries.

PMID- 25372497
TI  - Zebrafish Invade Valparaiso: Third Meeting and Symposium of the Latin American
      Zebrafish Network.
AB  - Abstract Zebrafish are an excellent model system for research and teaching.
      Because of their relatively low maintenance costs, beautiful and bountiful
      embryos, and tool box of molecular genetic technique, zebrafish are ideal for
      countries with smaller research budgets and less well-developed science
      infrastructure. For these reasons, zebrafish are growing in popularity as a model
      system for research in Latin America. In response to this growing need, we held
      the Third Latin American Zebrafish Network (LAZEN) Course and Symposium in
      Valparaiso, Chile, in April 4-13, 2014. The course covered a wide variety of
      topics from fish husbandry to outreach and ended with a symposium hosting
      excellent scientists from Latin America and beyond.

PMID- 25372498
TI  - Medicaid: 35 Years of Service.
AB  - On this 35th anniversary of the enactment of Medicaid, it is important to reflect
      on the program's role in the U.S. health care system. The Medicaid program is the
      third largest source of health insurance in the United States-after employer
      based coverage and Medicare. The significance of Medicaid's role in providing
      health insurance cannot be overstated. As the largest in the Federal safety net
      of public assistance programs, Medicaid provides essential medical and medically
      related services to the most vulnerable populations in society. In 1998, the
      Medicaid program covered 41.4 million low-income children, their families,
      elderly people, and individuals with disabilities-approximately 12 percent of the
      total U.S. population. Since its inception in 1965, Medicaid enrollment and
      expenditures have grown substantially. In addition, the program has evolved as
      Federal and State governments balance social, economic, and political factors
      affecting this and other public assistance programs. This article presents an
      overview of the Medicaid program and highlights trends in enrollment and
      expenditures.

PMID- 25372495
TI  - The specialized Hsp70 (HscA) interdomain linker binds to its nucleotide-binding
      domain and stimulates ATP hydrolysis in both cis and trans configurations.
AB  - Proteins from the isc operon of Escherichia coli constitute the machinery used to
      synthesize iron-sulfur (Fe-S) clusters for delivery to recipient apoproteins.
      Efficient and rapid [2Fe-2S] cluster transfer from the holo-scaffold protein IscU
      depends on ATP hydrolysis in the nucleotide-binding domain (NBD) of HscA, a
      specialized Hsp70-type molecular chaperone with low intrinsic ATPase activity
      (0.02 min(-1) at 25  degrees C, henceforth reported in units of min(-1)). HscB,
      an Hsp40-type cochaperone, binds to HscA and stimulates ATP hydrolysis to promote
      cluster transfer, yet while the interactions between HscA and HscB have been
      investigated, the role of HscA's interdomain linker in modulating ATPase activity
      has not been explored. To address this issue, we created three variants of the 40
      kDa NBD of HscA: NBD alone (HscA386), NBD with a partial linker (HscA389), and
      NBD with the full linker (HscA395). We found that the rate of ATP hydrolysis of
      HscA395 (0.45 min(-1)) is nearly 15-fold higher than that of HscA386 (0.035 min(
      1)), although their apparent affinities for ATP are equivalent. HscA395, which
      contains the full covalently linked linker peptide, exhibited intrinsic
      tryptophan fluorescence emission and basal thermostability that were higher than
      those of HscA386. Furthermore, HscA395 displayed narrower (1)H(N) line widths in
      its two-dimensional (1)H-(15)N TROSY-HSQC spectrum in comparison to HscA386,
      indicating that the peptide in the cis configuration binds to and stabilizes the
      structure of the NBD. The addition to HscA386 of a synthetic peptide with a
      sequence identical to that of the interdomain linker (L(387)LLDVIPLS(395))
      stimulated its ATPase activity and induced widespread NMR chemical shift
      perturbations indicative of a binding interaction in the trans configuration. 

PMID- 25372499
TI  - Assessing the fate of nutrients and carbon in the bioenergy chain through the
      modeling of biomass growth and conversion.
AB  - A forest growth model was coupled to a model of combined heat and power (CHP)
      production in a gasification plant developed in Aspen Plus. For a given
      production, this integrated forest-to-energy model made it possible to predict
      the annual flows in wood biomass, carbon, and nutrients, including N, S, P, and
      K, from the forest to the air emissions (NOx, SOx, PAH, etc.) and ash flows. We
      simulated the bioenergy potential of pure even-aged high-forest stands of
      European beech, an abundant forest type in Northeastern France. Two forest
      management practices were studied, a standard-rotation and a shorter-rotation
      scenario, along with two wood utilizations: with or without fine woody debris
      (FWD) harvesting. FWD harvesting tended to reduce the forested area required to
      supply the CHP by 15-22% since larger amounts of energy wood were available for
      the CHP process, especially in the short-rotation scenario. Because less biomass
      was harvested, the short-rotation scenario with FWD decreased the nutrient
      exports per hectare and year by 4-21% compared to standard practices but
      increased the amount of N, S, and P in the CHP process by 2-9%. This increase in
      the input nutrient flows had direct consequences on the inorganic air emissions,
      thus leading to additional NOx and SO2 emissions. This model is a valuable tool
      for assessing the life cycle inventories of the entire bioenergy chain.

PMID- 25372500
TI  - Medicaid Spending: A Brief History.
AB  - Medicaid spending growth has varied greatly over time. This article uses
      financial and statistical data to trace the history of Medicaid spending in
      relation to some of the major factors that have influenced its growth over the
      years. Periods of varying growth are divided into eight "eras," ranging from
      program startup in 1966 through the post-welfare reform period. Average
      expenditure and enrollee growth for each era are presented and briefly discussed.
      Finally, some factors are mentioned that are likely to affect future growth in
      the Medicaid program.

PMID- 25372501
TI  - The anti-proliferative effects of enterolactone in prostate cancer cells:
      evidence for the role of DNA licencing genes, mi-R106b cluster expression, and
      PTEN dosage.
AB  - The mammalian lignan, enterolactone, has been shown to reduce the proliferation
      of the earlier stages of prostate cancer at physiological concentrations in
      vitro. However, efficacy in the later stages of the disease occurs at
      concentrations difficult to achieve through dietary modification. We have
      therefore investigated what concentration(s) of enterolactone can restrict
      proliferation in multiple stages of prostate cancer using an in vitro model
      system of prostate disease. We determined that enterolactone at 20 MUM
      significantly restricted the proliferation of mid and late stage models of
      prostate disease. These effects were strongly associated with changes in the
      expression of the DNA licencing genes (GMNN, CDT1, MCM2 and 7), in reduced
      expression of the miR-106b cluster (miR-106b, miR-93, and miR-25), and in
      increased expression of the PTEN tumour suppressor gene. We have shown anti
      proliferative effects of enterolactone in earlier stages of prostate disease than
      previously reported and that these effects are mediated, in part, by microRNA
      mediated regulation. 

PMID- 25372502
TI  - Association of alkanes with the aqueous liquid-vapor interface: a reference
      system for interpreting hydrophobicity generally through interfacial
      fluctuations.
AB  - We report free energy calculations and fluctuation profiles of single alkanes
      (from methane to pentane) along the direction normal to the air-water interface.
      The induced fluctuations and the interfacial stabilities of alkanes are found to
      be correlated and similar to the results of inorganic monovalent ions (Ou et al.,
      J. Phys. Chem. B, 2013, 117, 11732). This suggests that hydrophobic solvation of
      solutes and ions is important in determining the adsorption behavior. 

PMID- 25372503
TI  - Chronic myeloid leukemia drug evaluation using a multisignal amplified
      photoelectrochemical sensing platform.
AB  - Chronic myeloid leukemia (CML) is a malignant clone disease of hematopoietic stem
      cells. At present, the most effective therapy for CML is bone marrow
      transplantation, but this procedure is expensive, and it is often difficult to
      find appropriately matched bone marrow donors. As an alternative to marrow
      transplantation, a more effective anticancer drug should be developed to cure the
      disease; in addition, an effective system to evaluate the activity of the drug
      needs to be developed. Herein, we present a novel antileukemia drug evaluation
      method based on a multisignal amplified photoelectrochemical sensing platform
      that monitors the activity of caspase-3, a known marker of cell apoptosis.
      Manganese-doped CdS@ZnS core-shell nanoparticles (Mn:CdS@ZnS) were synthesized
      via a simple wet chemical method, which provided a stable photocurrent signal. A
      DEVD-biotin peptide and streptavidin-labeled alkaline phosphatise (SA-ALP) were
      immobilized successively at these nanoparticles through amide bonding and through
      specific interaction between biotin and streptavidin, respectively. The
      photocurrent of this sensing platform improved as the ALP hydrolyzed the
      substrate 2-phospho-l-ascorbic acid (AAP) to ascorbic acid (AA), a more efficient
      electron donor. The activity of caspase-3 was detected using this sensing
      platform, and thus, the efficacy of nilotinib for targeting K562 CML cells could
      be evaluated. The results indicate that nilotinib can effectively induce
      apoptosis of the K562 cells. This sensing platform exhibited sensitive,
      reproductive, and stable performance in studying the nilotinib-induced apoptosis
      of K562 CML cells, and the platform could be utilized to evaluate other
      anticancer drugs. 

PMID- 25372504
TI  - Antireflective coatings with adjustable refractive index and porosity synthesized
      by micelle-templated deposition of MgF2 sol particles.
AB  - Minimizing efficiency losses caused by unwanted light reflection at the interface
      between lenses, optical instruments and solar cells with the surrounding medium
      requires antireflective coatings with adequate refractive index and coating
      thickness. We describe a new type of antireflective coating material with easily
      and independently tailorable refractive index and coating thickness based on the
      deposition of colloidal MgF2 nanoparticles. The material synthesis employs
      micelles of amphiphilic block copolymers as structure directing agent to
      introduce controlled mesoporosity into MgF2 film. The coatings thickness can be
      easily adjusted by the applied coating conditions. The coatings refractive index
      is determined by the materials porosity, which is controlled by the amount of
      employed pore template. The refractive index can be precisely tuned between 1.23
      and 1.11, i.e., in a range that is not accessible to nonporous inorganic
      materials. Hence, zero reflectance conditions can be established for a wide range
      of substrate materials. 

PMID- 25372505
TI  - Minority Health Status in Adulthood: The Middle Years.
AB  - The objective of this article is to describe the racial and ethnic differences in
      health status during the "middle years" of life. We use data from National Vital
      Statistics Reports (Hoyert, Kochanek, and Murphy, 1999) to estimate excess
      mortality among racial and ethnic minority groups for the leading causes of death
      among adults. Also discussed are the current state of scholarship in minority
      health and suggestions for future directions for research on racial and ethnic
      differences in health status.

PMID- 25372506
TI  - Unusual reactivity of nitronates with an aryl alkyl carbonate: synthesis of alpha
      amino esters.
AB  - The monoanions of nitroalkanes are ambident nucleophiles that react with
      carbonate electrophiles through the oxygen atom. Products arising from reactivity
      at the carbon atom will yield alpha-nitro esters, which are precursors for alpha
      amino esters. We demonstrate this in the reactions of nitroalkanes with benzyl
      phenyl carbonate and DABCO where alpha-nitro esters are obtained instead of
      nitrile oxides. The products are readily reduced to alpha-amino esters. This
      pathway could be a safe alternative to the Strecker reaction. 

PMID- 25372507
TI  - Intra-arterial delivery of human bone marrow mesenchymal stem cells is a safe and
      effective way to treat cerebral ischemia in rats.
AB  - Cerebral ischemic stroke is a very common condition that can cause death and
      disability. Studies have confirmed that stem cells have therapeutic effects if
      administered after a stroke. There is still a great deal of debate regarding the
      best route for cell transplantation. Intravascular delivery is the most commonly
      used one. In this study, the therapeutic effects of bone marrow stem cells
      (BMSCs) delivered by intra-arterial (IA) and intravenous (IV) injection in a rat
      transient middle cerebral artery occlusion model (MCAO) are compared.
      Histological analysis demonstrated that the IA route bypasses the pulmonary
      system and directs the cells to the ischemic parts of the brain more efficiently.
      The BMSCs delivered via the IA route promoted angiogenesis and improved
      functional recovery. The cerebral blood flow (CBF) of the rats was monitored
      during the IA injection process. No reduction in CBF or microstrokes was
      detected. Brain perfusion and metabolism, as evaluated by SPECT and PET, were
      better in rats treated with cells delivered via IA. Results showed that the IA
      route is a safe and effective way to transplant hBMSCs. This manuscript is
      published as part of the International Association of Neurorestoratology (IANR)
      special issue of Cell Transplantation. 

PMID- 25372508
TI  - Multilayer transfer printing of electroactive thin film composites.
AB  - We demonstrate the high fidelity transfer printing of an electroactive polymer
      nanocomposite thin film onto a conductive electrode. Polyelectrolyte multilayer
      thin films of thickness ~200 nm containing 68 vol % Prussian Blue nanoparticles
      are assembled on a UV-curable photopolymer stamp and transferred in their
      entirety onto ITO-coated glass creating ~2.5 MUm-wide line patterns with ~1.25
      MUm spacing. AFM and SEM are used to investigate pattern fidelity and morphology,
      while cyclic voltammetry confirms the electroactive nature of the film and
      electrical connectivity with the electrode. The patterning strategy presented
      here could be used to pattern electroactive thin films containing a high density
      of nanoparticles onto individually addressable microelectrodes for a variety of
      applications ranging from biosensor arrays to flexible electronics. 

PMID- 25372509
TI  - A twist on facial selectivity of hydride reductions of cyclic ketones: twist-boat
      conformers in cyclohexanone, piperidone, and tropinone reactions.
AB  - The role of twist-boat conformers of cyclohexanones in hydride reductions was
      explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an
      N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a
      bulky borohydride reagent were investigated computationally and compared to
      experiment. Our results indicate that in certain cases, factors such as substrate
      conformation, nucleophile bulkiness, and remote steric features can affect
      stereoselectivity in ways that are difficult to predict by the general Felkin-Anh
      model. In particular, we have calculated that a twist-boat conformation is
      relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6
      disubstituted N-acylpiperidones with a small hydride reagent (LiAlH4) but not
      with a bulky hydride (lithium triisopropylborohydride). 

PMID- 25372510
TI  - Population pharmacokinetics of intravenous artesunate: a pooled analysis of
      individual data from patients with severe malaria.
AB  - There are ~660,000 deaths from severe malaria each year. Intravenous artesunate
      (i.v. ARS) is the first-line treatment in adults and children. To optimize the
      dosing regimen of i.v. ARS, the largest pooled population pharmacokinetic study
      to date of the active metabolite dihydroartemisinin (DHA) was performed. The
      pooled dataset consisted of 71 adults and 195 children with severe malaria, with
      a mixture of sparse and rich sampling within the first 12 h after drug
      administration. A one-compartment model described the population pharmacokinetics
      of DHA adequately. Body weight had the greatest impact on DHA pharmacokinetics,
      resulting in lower DHA exposure for smaller children (6-10 kg) than adults. Post
      hoc estimates of DHA exposure were not significantly associated with
      parasitological outcomes. Comparable DHA exposure in smaller children and adults
      after i.v. ARS was achieved under a dose modification for intramuscular ARS
      proposed in a separate analysis of children. 

PMID- 25372512
TI  - Osteoblast proliferation is enhanced upon the insulin receptor substrate 1
      overexpression via PI3K signaling leading to down-regulation of NFkappaB and BAX
      pathway.
AB  - The insulin receptor substrate 1 (IRS1) promotes bone formation via osteoblast
      proliferation mediated by PI3K/Akt signaling. A reduction in NFkappaB activity in
      osteoblasts results in an increase in bone formation. The NFkappaB signaling
      pathway leads to increased expression of BAX, which contributes to osteoblast
      apoptosis. The purpose of this study was to investigate the expression of
      recombinant plasmid enhanced green fluorescent protein-N1 (pEGFP-N1) that
      transferred IRS1 gene into osteoblasts in vitro and evaluate the effects of IRS1
      overexpression on NFkappaBp65 and on BAX. Osteoblasts were transfected with pEGFP
      N1 or pEGFP-N1 encoding wild-type IRS1 (pEGFP-N1-IRS1). Cell cycle analysis was
      performed using flow cytometry. The expression levels of NFkappaBp65 and BAX were
      measured by Western blotting. Our results revealed that overexpression of IRS1
      stimulated osteoblast proliferation, as evidenced by an increase in the number of
      cells in the S phase compared to controls. IRS1 overexpression in osteoblasts
      activated the PI3K/Akt pathway, and inhibited expression of NFkappaBp65 and BAX.
      When osteoblasts transfected with pEGFP-N1-IRS1 were exposed to a PI3K inhibitor
      (LY294002), the effects of IRS1 overexpression were reversed. On the basis of our
      study, it seems that osteoblasts proliferated upon IRS1 overexpression due to
      inhibition of the NFkappaB pathway and downregulation of BAX through PI3K/Akt
      signaling. 

PMID- 25372511
TI  - Multicenter prospective cohort study of the incidence of adverse events
      associated with cosmetic dermatologic procedures: lasers, energy devices, and
      injectable neurotoxins and fillers.
AB  - IMPORTANCE: Common noninvasive to minimally invasive cosmetic dermatologic
      procedures are widely believed to be safe given the low incidence of reported
      adverse events, but reliable incidence data regarding adverse event rates are
      unavailable to date. OBJECTIVE: To assess the incidence of adverse events
      associated with noninvasive to minimally invasive cosmetic dermatologic
      procedures, including those involving laser and energy devices, as well as
      injectable neurotoxins and fillers. DESIGN, SETTING, AND PARTICIPANTS: A
      multicenter prospective cohort study (March 28, 2011, to December 30, 2011) of
      procedures performed using laser and energy devices, as well as injectable
      neurotoxins and soft-tissue augmentation materials, among 8 geographically
      dispersed US private and institutional dermatology outpatient clinical practices
      focused on cosmetic dermatology, with a total of 23 dermatologists. Participants
      represented a consecutive sample of 20 399 cosmetic procedures. Data acquisition
      was for 3 months (13 weeks) per center, with staggered start dates to account for
      seasonal variation. EXPOSURES: Web-based data collection daily at each center to
      record relevant procedures, by category type and subtype. Adverse events were
      detected by (1) initial observation by participating physicians or staff; (2)
      active ascertainment from patients, who were encouraged to self-report after
      their procedure; and (3) follow-up postprocedural phone calls to patients by
      staff, if appropriate. When adverse events were not observed by physicians but
      were suspected, follow-up visits were scheduled within 24 hours to characterize
      these events. Detailed information regarding each adverse event was entered into
      an online form. MAIN OUTCOMES AND MEASURES: The main outcome was the total
      incidence of procedure-related adverse events (total adverse events divided by
      total procedures performed), as verified by clinical examination. RESULTS: Forty
      eight adverse events were reported, for a rate of 0.24% (95% CI, 0.18%-0.31%).
      Overall, 36 procedures resulted in at least 1 adverse event, for a rate of 0.18%
      (95% CI, 0.13%-0.25%). No serious adverse events were reported. Adverse events
      were infrequently associated with known risk factors. CONCLUSIONS AND RELEVANCE:
      Noninvasive to minimally invasive cosmetic dermatologic procedures, including
      energy, neurotoxin, and filler procedures, are safe when performed by experienced
      board-certified dermatologists. Adverse events occur in less than 1% of patients,
      and most of these are minor and transient.

PMID- 25372513
TI  - Ultrasmooth gold surfaces prepared by chemical mechanical polishing for
      applications in nanoscience.
AB  - For over 20 years, template stripping has been the best method for preparing
      ultrasmooth metal surfaces for studies of nanostructures. However, the organic
      adhesives used in the template stripping method are incompatible with many
      solvents, limiting the conditions that may subsequently be used to prepare
      samples; in addition, the film areas that can be reliably prepared are typically
      limited to ~1 cm(2). In this article, we present chemical-mechanical polishing
      (CMP) as an adhesive-free, scalable method of preparing ultrasmooth gold
      surfaces. In this process, a gold film is first deposited by e-beam evaporation
      onto a 76-mm-diameter silicon wafer. The CMP process removes ~4 nm of gold from
      the tops of the grains comprising the gold film to produce an ultrasmooth gold
      surface supported on the silicon wafer. We measured root-mean-square (RMS)
      roughness values using atomic force microscopy of 12 randomly sampled 1 MUm * 1
      MUm areas on the surface of the wafer and repeated the process on 5 different CMP
      wafers. The average RMS roughness was 3.8 +/- 0.5 A, which is comparable to
      measured values for template-stripped gold (3.7 +/- 0.5 A). We also compared the
      use of CMP and template-stripped gold as bottom electrical contacts in molecular
      electronic junctions formed from n-alkanethiolate self-assembled monolayers as a
      sensitive test bed to detect differences in the topography of the gold surfaces.
      We demonstrate that these substrates produce statistically indistinguishable
      values for the tunneling decay coefficient beta, which is highly sensitive to the
      gold surface topography. 

PMID- 25372514
TI  - A luminescent cadmium metal-organic framework for sensing of nitroaromatic
      explosives.
AB  - A novel metal-organic framework [Cd3(TPT)2(DMF)2].(H2O)0.5 (1) has been
      solvothermally synthesized using a new rigid unsymmetrical tricarboxylate ligand
      p-terphenyl-3,4'',5-tricarboxylic acid (H3TPT). Single-crystal X-ray diffraction
      analysis reveals that 1 possesses a three-dimensional (3D) framework with an alb
      4,8-C2/c topology constructed by the combination of Cd-carboxylate chains and TPT
      linkers. The pi-electron rich ligand H3TPT enables 1 to have an excellent
      luminescent property. The micrometer-sized compound 1' dispersed in ethanol
      exhibits high efficiency detection for picric acid (PA). The high efficiency,
      stability and recyclability of 1' make it a potential chemosensor for
      nitroaromatic explosives.

PMID- 25372515
TI  - Retinal Cases & Brief Reports. Editorial.

PMID- 25372516
TI  - Seronegative granulomatous polyangiitis with central retinal artery occlusion as
      the initial manifestation.
AB  - PURPOSE: To report a case of central retinal artery occlusion in a patient with
      autopsy-verified granulomatous polyangiitis (GP) with negative cytoplasmic
      antineutrophil cytoplasmic antibody. METHODS: Case report. RESULTS: A 61-year-old
      Hispanic man with history of tuberculosis was admitted to the hospital with
      worsening dyspnea. Two weeks later, he experienced sudden vision loss due to
      central retinal artery occlusion in his right eye. A CT of the lung revealed
      multiple opacities. He developed renal failure during his hospital stay. A serum
      cytoplasmic antineutrophil cytoplasmic antibody test was negative. Pulmonary
      biopsy disclosed chronic inflammation with no evidence of granuloma formation or
      vasculitis. He died of acute respiratory distress due to bilateral deep vein
      thrombosis of his lower extremities. Autopsy revealed GP. CONCLUSION:
      Granulomatous polyangiitis is a multisystem vasculitic disorder. Central retinal
      artery occlusion as the presenting manifestation of GP is very uncommon. This
      report demonstrates the difficulty of diagnosing GP, particularly when initial
      diagnostic assays (including both serology and biopsy) were negative for GP.

PMID- 25372517
TI  - Bilateral macular detachments, venous stasis retinopathy, and retinal hemorrhages
      as initial presentation of multiple myeloma: a case report.
AB  - PURPOSE: To present the case of a patient with bilateral macular detachments,
      venous stasis retinopathy, and retinal hemorrhages as the initial manifestation
      of multiple myeloma. METHODS: Case report. RESULTS: A 59-year-old woman presented
      with complaints of photopsias and decreased vision and was found to have
      bilateral macular detachments, venous stasis retinopathy, and retinal
      hemorrhages. Fluorescein angiography revealed an angiographically silent fundus
      in both eyes, indicating no fluorescein leakage was found in the macula. Workup
      revealed multiple myeloma as the cause of the retinal findings. CONCLUSION:
      Macular detachment or subretinal fluid, retinal venous dilation or congestion,
      and retinal hemorrhages may be presenting signs of multiple myeloma.

PMID- 25372518
TI  - Purtscher-like retinopathy after prostate surgery.
AB  - PURPOSE: To describe a case of Purtscher-like retinopathy after uncomplicated
      radical prostatectomy. METHODS: Observational case report. RESULTS: Purtscher
      retinopathy is named after the Austrian ophthalmologist Othmar Purtscher (1852
      1927) who first fully described the syndrome of "traumatic retinal angiopathy" in
      1912 as patches of retinal whitening, retinal hemorrhages, and disk edema after
      compression injury to the head. Since that time, similar findings, often called
      Purtscher-like retinopathy, have been described in association with a number of
      conditions, including, among others, acute pancreatitis, chest compression
      injury, childbirth, and fat embolism syndrome, after long-bone fracture or
      surgery. CONCLUSION: The occurrence of Purtscher-like changes after nonorthopedic
      surgery seems, however, to be rare. The authors describe a single case of
      Purtscher-like retinopathy after uncomplicated radical prostatectomy.

PMID- 25372519
TI  - Best disease presenting as a giant serous pigment epithelial detachment.
AB  - PURPOSE: To report a case of Best disease presenting as a giant serous pigment
      epithelial detachment and misdiagnosed as central serous chorioretinopathy.
      METHODS: Clinical examination and multimodal imaging, including color fundus
      photography, fluorescein angiography, fundus autofluorescence, and spectral
      domain optical coherence tomography are presented, as well as the results of
      electrooculography. RESULTS: A 54-year-old Asian man underwent photodynamic
      therapy for a large serous pigment epithelial detachment presumed to be due to
      central serous chorioretinopathy. When the lesion was recalcitrant to therapy,
      further investigation revealed severely decreased Arden ratios consistent with
      Best disease. CONCLUSION: There is a wide spectrum in the clinical presentation
      of Best disease. Diagnostic uncertainty can be elucidated with fundus
      autofluorescence, spectral domain optical coherence tomography imaging,
      electrooculography, and genetic testing.

PMID- 25372520
TI  - Multiple bilateral branch retinal artery occlusions in a patient with sickle cell
      disease with vancomycin red man syndrome.
AB  - PURPOSE: To report a case of multiple bilateral branch retinal artery occlusions
      associated with vancomycin infusion in an African American patient in acute
      sickle crisis. METHODS: Single case report. RESULTS: A 30-year-old man with
      complicated sickle cell disease presented with pain, fever, and hypoxia. During
      infusion of vancomycin, he became diaphoretic, hypotensive, and unresponsive, and
      exhibited respiratory distress and a disseminated red skin rash consistent with a
      severe allergic reaction referred to as the red man syndrome. When the patient
      regained consciousness within an hour, he complained of severe vision loss and
      demonstrated multiple bilateral branch retinal artery occlusions. Within 4 days,
      visual acuity recovered to 20/20 in the right eye but remained hand motions in
      the left eye. CONCLUSION: Retinal artery occlusion is a rare but potentially
      devastating complication of sickle cell disease. The potential for complications
      from vancomycin infusion during acute sickle crisis should be considered,
      although further study is warranted.

PMID- 25372521
TI  - Combined retinoschisis-detachment involving the fovea managed with observation.
AB  - PURPOSE: To report a case of a combined retinoschisis-detachment progressing to
      foveal involvement managed by observation. METHODS: This is a case report with a
      19-month follow-up period. Clinical examination, fundus photography, and optical
      coherence tomography were used to follow the retinal findings over time. RESULTS:
      A 61-year-old man presented with 20/20 vision with a retinoschisis-detachment.
      The detachment progressed to involve the fovea, and the vision declined to 20/40.
      The patient was observed for 14 months, and his vision remained 20/40. Optical
      coherence tomography demonstrated a stable detachment. CONCLUSION: Retinal
      detachment may occur within retinoschisis. Despite foveal detachment, patients
      may maintain good vision without surgical intervention.

PMID- 25372522
TI  - Clinical presentation of chorioretinitis sclopetaria.
AB  - PURPOSE: To report the clinical manifestations of a case of chorioretinitis
      sclopetaria. METHODS: Observational case report. RESULTS: A 30-year-old prison
      inmate sustained a traumatic injury to his left eye. Fundus examination showed a
      large chorioretinal detachment revealing bare sclera, vitreous hemorrhage, and
      commotio retinae. CONCLUSION: The patient was diagnosed with chorioretinitis
      sclopetaria. Given the mechanism of injury, retinal detachment is rare.
      Observation is appropriate as initial management.

PMID- 25372523
TI  - Acute retinal necrosis secondary to multidrug-resistant herpes simplex virus 2 in
      an immunocompetent adolescent.
AB  - PURPOSE: To report the clinical course of a patient with acute retinal necrosis
      resulting from a multidrug-resistant strain of herpes simplex virus 2. METHODS:
      Observational case report. RESULTS: A 17-year-old man with no identifiable immune
      deficiency presented with pain and decreased vision in his left eye. He had dense
      anterior and posterior segment inflammation with retinal whitening suggestive of
      acute retinal necrosis, which progressed despite treatment with intravenous
      acyclovir, methylprednisolone, and ganciclovir. A transition to intravitreal and
      intravenous foscarnet led to clinical improvement. Genetic analysis revealed the
      etiology to be a multidrug-resistant strain of herpes simplex virus 2.
      CONCLUSION: Antiviral resistance is an uncommon finding among viruses causing
      acute retinal necrosis in immunocompetent patients. Patients with these
      infections may be adequately treated with prompt recognition and a change in
      therapy to alternative antiviral agents such as foscarnet.

PMID- 25372524
TI  - Chronic exogenous exophiala dermatitidis endophthalmitis.
AB  - PURPOSE: To describe a case of chronic exogenous Exophiala dermatitidis
      endophthalmitis. METHODS: Retrospective chart review and case report. RESULTS: A
      60-year-old man with history of chronic herpes zoster keratitis complicated by
      secondary fungal keratitis treated with penetrating keratoplasty presented with a
      white cataract, chronic anterior uveitis, and counting fingers vision in the left
      eye. Combined cataract extraction and diagnostic vitrectomy revealed positive
      cultures and polymerase chain reaction-based testing for E. dermatitidis-the same
      organism responsible for the keratitis. The patient was treated with multiple
      oral, intravenous, and intravitreal antifungal agents. Ultimately, the corneal
      infection recurred and the patient elected to undergo enucleation. Filamentous
      fungi consistent with E. dermatitidis infection were identified in the cornea of
      the enucleation specimen. CONCLUSION: Although rare, Exophiala species can cause
      exogenous endophthalmitis. Chronic endophthalmitis should be suspected in
      patients who develop persistent intraocular inflammation after infectious
      keratitis.

PMID- 25372525
TI  - Paraneoplastic vitelliform retinopathy in a patient with treated choroidal
      melanoma.
AB  - PURPOSE: To describe a peculiar case of paraneoplastic vitelliform
      maculopathy/retinopathy in a patient with treated choroidal melanoma. METHODS: A
      case report of a 58-year-old woman with a history of treated choroidal melanoma
      16 years before developing visual changes in the setting of metastatic choroidal
      melanoma. RESULTS: We demonstrate bilateral, multifocal vitelliform subretinal
      lesions and focal, neurosensory retinal detachment associated with metastatic
      melanoma. CONCLUSION: Paraneoplastic vitelliform maculopathy/retinopathy should
      be considered in patients with or without a history of melanoma, who have
      unexplained serous, vitelliform retinal detachments, especially with atypical or
      absence of leakage on fluorescein angiography.

PMID- 25372526
TI  - Headache and whiteout vision as the presenting symptoms in a case of Takayasu
      retinopathy.
AB  - PURPOSE: To report a case of Takayasu retinopathy presenting as chronic headache
      and whiteout of vision. METHODS: A case report of a 28-year-old woman with no
      medical history diagnosed with Takayasu retinopathy after a complete
      ophthalmologic examination, including widefield fluorescein angiography. RESULTS:
      Dilated fundus examination revealed sharp margins in both eyes and mildly
      attenuated arterioles and distended veins. The peripheral examination was
      significant for several white-centered intraretinal hemorrhages. A widefield
      fluorescein angiogram showed numerous small microaneurysms in the periphery. A
      computer tomography angiogram of the chest showed central wall thickening of the
      aortic arch, proximal branch vessels of the aortic arch, including left common
      carotid and right common carotid, and middle lower lobe of the right pulmonary
      artery, all of which were consistent with the diagnosis of Takayasu disease. The
      patient underwent cardiovascular bypass surgery and her ocular symptoms resolved.
      CONCLUSION: Up to one third of patients with Takayasu disease experience visual
      disturbances, and as a result, ophthalmologists may be the first physicians to
      encounter and diagnose this condition. The various stages of Takayasu retinopathy
      are characterized by dilation of small vessels, capillary microaneurysm
      formation, and development of arterial-venous anastomoses. The initial clinical
      presentation of Takayasu disease can be varied and nonspecific, therefore a high
      index of clinical suspicion is essential for diagnosis.

PMID- 25372527
TI  - Bilateral subinternal limiting membrane hemorrhage in benzene toxicity.
AB  - PURPOSE: To report the clinical and spectral domain optical coherence tomography
      findings in a patient with bilateral central vision loss and a history of
      exposure to polyamides. METHODS: The clinical presentation of the patient was
      documented with color fundus photographs and spectral domain optical coherence
      tomography. The patient was a 20-year-old male factory worker with no medical
      history who was initially admitted for workup of hematologic malignancy due to
      petechiae and fevers. RESULTS: Optical coherence tomography revealed bilateral
      hemorrhages in the subinternal limiting membrane space resembling Valsalva
      retinopathy. Complete blood count revealed pancytopenia and marked
      thrombocytopenia. CONCLUSION: Heavy exposure to benzene, a byproduct of the
      polyamide-curing process, is known to cause aplastic anemia. Accompanying
      thrombocytopenia may increase the risk of spontaneous subinternal limiting
      membrane hemorrhage.

PMID- 25372528
TI  - Leukemia presenting as serous retinal detachment.
AB  - BACKGROUND: To describe a patient who presented with bilateral serous retinal
      detachments without the other retinal vascular or ocular inflammatory signs, and
      who was ultimately diagnosed with acute leukemia. METHODS: Case report and review
      of the literature. RESULTS: This patient presented with isolated bilateral serous
      retinal detachments as the initial manifestation of hematologic malignancy.
      CONCLUSION: Acute leukemia may present with serous retinal detachments without
      the signs of other retinopathy or ocular inflammation. Incorrect diagnosis may
      delay detection and proper management of the malignancy. Leukemia should be
      considered in the differential diagnosis of isolated serous retinal detachments.

PMID- 25372529
TI  - Spectral domain optical coherence tomography imaging of Purtscher-like
      retinopathy.
AB  - PURPOSE: To report spectral domain optical coherence tomography findings in a
      patient with Purtscher-like retinopathy. METHODS: Case report, image analysis,
      and literature review. RESULTS: A 71-year-old woman presented with decreased
      vision, cotton-wool spots, and a deep whitish polygonal lesion in her left eye,
      which was hyperreflective on spectral domain optical coherence tomography. She
      was diagnosed with Purtscher-like retinopathy and later was found to have
      metastatic pancreatic cancer. CONCLUSION: Purtscher-like retinopathy can occur
      secondary to malignant pancreatic cancer. Purtscher-flecken can be characterized
      by cross-sectional and en face spectral domain optical coherence tomography and
      represent deep capillary ischemia.

PMID- 25372530
TI  - Congenital optic nerve anomaly and migration of subretinal oil: case report and
      observations in one family.
AB  - PURPOSE: To describe a case of optic nerve (ON) anomaly and retinal detachment
      with extensive subretinal silicone oil after repair of retinal detachment. A
      three-generation family history of ON anomaly, two generations with detachment,
      is presented. METHODS: Retrospective chart review. A multigenerational family
      with ON anomalies and macular detachment. RESULTS: Final repair of retinal
      detachment was achieved using retinotomy for removal of subretinal 5,000
      centistoke silicone oil, gas-fluid exchange, and peripapillary photocoagulation.
      Silicone oil had been previously used successfully in this eye, yet on subsequent
      use resulted in subretinal migration. A four patient-three-generation family
      history of ON anomalies was elicited, and three members were photographed for
      documentation. CONCLUSION: Optic nerve anomalies and macular detachment present a
      treatment dilemma because they are associated with poor vision and often a
      suboptimal visual outcome after surgery. This case demonstrates a large amount of
      subretinal silicone oil, which migrated over a 2-month period. This case series
      is a report of a three-generational family demonstrating variable expressivity of
      ON anomalies complicated by macular detachment in two generations.

PMID- 25372531
TI  - A new choroidal mass in a patient with known metastatic leiomyosarcoma:
      importance of fine-needle aspirate biopsy in diagnostic certainty and treatment
      planning.
AB  - PURPOSE: To report a patient with known metastatic leiomyosarcoma and a new
      choroidal mass wherein a fine-needle aspirate biopsy was performed to achieve
      diagnostic and treatment certainty. METHODS: A retrospective case report of one
      patient. RESULTS: A 63-year-old woman with known metastatic leiomyosarcoma
      presented with a new choroidal mass. Metastatic leiomyosarcoma to the choroid has
      been previously reported. An ab externo fine-needle aspirate biopsy was performed
      to achieve diagnostic and therapeutic certainty (metastatic leiomyosarcoma is
      considered radiation insensitive and requires local excision, and choroidal
      melanoma is treated with I135 plaque brachytherapy). The results were positive
      for choroidal melanoma as read by two different pathologists at two different
      sites, and the patient was treated in the conventional manner. The response to
      treatment at 30 months has been excellent. CONCLUSION: When there is diagnostic
      uncertainty and treatment regimens vary, a fine-needle aspirate biopsy can be
      diagnostic and can provide direction for care. De novo tumors can be confounded
      with a metastatic disease in patients with complex histories.

PMID- 25372532
TI  - Multifocal serous detachments as the presenting sign of thrombotic
      thrombocytopenic purpura.
AB  - PURPOSE: To report a case of bilateral multifocal serous detachments as the
      presenting sign of thrombotic thrombocytopenic purpura. METHODS: Observational
      case report. RESULTS: A 59-year-old woman presented with decreased vision and was
      found to have bilateral multifocal serous detachments. Her review of symptoms
      prompted further investigations that revealed evidence of acute intravascular
      hemolysis, renal failure, and cerebral ischemia. This led to the diagnosis of
      thrombotic thrombocytopenic purpura. CONCLUSION: Thrombotic thrombocytopenic
      purpura is a life-threatening condition that may present to an ophthalmologist.
      Recognizing its ophthalmic manifestations can be life saving for the patient.

PMID- 25372533
TI  - Significant macular edema in a patient with cone dystrophy and improvement with
      acetazolamide treatment.
AB  - PURPOSE: To describe a unique presentation and treatment course of a patient with
      an established diagnosis of cone dystrophy. METHODS: Clinical examination,
      spectral domain optical coherence tomography, autofluorescence, fluorescein
      angiography, and electrophysiology testing were evaluated. RESULTS: A patient
      with cone dystrophy diagnosed by clinical examination and electrophysiology
      testing displayed a large amount of macular intraretinal and subretinal fluid on
      spectral domain optical coherence tomography in both eyes, without obvious
      angiographic leakage. Intraretinal fluid resolved after 7 weeks treatment on oral
      acetazolamide therapy. The patient had subjective improvement in peripheral
      vision, though the visual acuity remained the same. CONCLUSION: Patients with
      cone dystrophy can accumulate intraretinal edema in the macula, which may respond
      to carbonic anhydrase therapy.

PMID- 25372534
TI  - Multimodal imaging in a case of deferoxamine-induced maculopathy.
AB  - PURPOSE: To report a case of deferoxamine-induced maculopathy and present the use
      of multimodal retinal imaging to study this disease entity. METHODS: This is an
      observational case report of one patient. Multimodal imaging with fundus
      autofluorescence, infrared imaging, and spectral domain optical coherence
      tomography was used to investigate the macular changes induced by deferoxamine
      toxicity. RESULTS: A 53-year-old man with history of beta-thalassemia presented
      with decreased vision in both eyes 1 month after initiating deferoxamine therapy.
      Infrared imaging showed areas of increased stippled infrared intensity through
      the macula. Fundus autofluorescence revealed diffuse areas of stippled
      hyperautofluorescence and hypoautofluorescence. Spectral domain optical coherence
      tomography changes included disruption of the ellipsoid zone, attenuation of the
      photoreceptors, and deposits within the retinal pigment epithelium. CONCLUSION: A
      case of deferoxamine-induced maculopathy was described and the use of multimodal
      retinal imaging to study this disease entity was presented.

PMID- 25372535
TI  - Subclinical hypercortisolism in central serous chorioretinopathy.
AB  - PURPOSE: To describe a case of a patient with chronic central serous
      chorioretinopathy who was found to have an adrenocorticotropin-secreting
      pituitary microadenoma despite the absence of many clinical signs of Cushing
      syndrome. METHODS: A retrospective chart review was performed. This study
      included a 42-year-old white woman with a history of chronic central serous
      chorioretinopathy. RESULTS: The patient was found to have severe osteoporosis;
      although many of the classic signs of Cushing syndrome were absent, laboratory
      studies and neuroimaging suggested the presence of a pituitary microadenoma.
      Ophthalmic evaluation revealed the presence of bilateral submacular fluid because
      of chronic multifocal central serous chorioretinopathy. The patient underwent
      bilateral photodynamic therapy and surgical excision of the pituitary lesion.
      Pathologic evaluation confirmed that the pituitary lesion was a pituitary
      microadenoma. CONCLUSION: Careful attention to the signs of hypercortisolism in
      patients with central serous chorioretinopathy may aid in detecting underlying
      systemic pathology. Endocrinology evaluations in patients presenting with any
      manifestations of Cushing syndrome may be warranted, even if many classic
      physical findings are absent.

PMID- 25372536
TI  - Sequential multimodal imaging findings in a case of primary vitreoretinal
      lymphoma.
AB  - PURPOSE: To report the utility of multimodal imaging including color photography,
      fundus autofluorescence (FAF), and spectral domain optical coherence tomography
      in a case of primary vitreoretinal lymphoma. METHODS: Color photographs, FAF, and
      the spectral domain optical coherence tomography images were performed at
      baseline and through 12 months of follow-up. RESULTS: At baseline and follow-up
      visits, spectral domain optical coherence tomography and FAF were more sensitive
      than color photography in showing the extent of disease. With treatment, spectral
      domain optical coherence tomography showed resolution of subretinal
      hyperreflective material while FAF imaging showed a reduction in hyperreflective
      dots, which were present at baseline. CONCLUSION: Spectral domain optical
      coherence tomography and FAF were more sensitive than color photographs in
      showing the disease extent and response to treatment. These imaging techniques
      may supplement other metrics used to monitor the patients with primary
      vitreoretinal lymphoma.

PMID- 25372537
TI  - Localized retinal manifestations of paraneoplastic autoimmune retinopathy.
AB  - PURPOSE: Systemic neoplastic processes can affect the retina through autoimmune
      retinopathy. This process may present in a variety of patterns. A novel pattern
      of paraneoplastic autoimmune retinopathy has been described. METHODS: Two
      patients presented with paraneoplastic vision changes. Optical coherence
      tomography and multifocal electroretinography were performed, which showed a
      unique focal retinal change in both patients. Case 1 is a 20-year-old woman with
      history of cutaneous melanoma. Case 2 is 67-year-old woman with history of breast
      cancer. RESULTS: Both patients showed a localized area of foveal thinning that
      corresponded with areas of depression on multifocal electroretinography. Each
      tested positive for antiretinal antibodies. CONCLUSION: This is a novel
      manifestation of paraneoplastic autoimmune retinopathy. Previously described
      cases have all affected the retina diffusely. These cases highlight the need to
      consider distant neoplastic processes when evaluating patient with similar
      presentations to those depicted here.

PMID- 25372538
TI  - Severe visual loss secondary to retinal toxicity after intravenous use of
      bisphosphonate in an eye with known chloroquine maculopathy.
AB  - PURPOSE: To describe a case of retinal toxicity after intravenous administration
      of the bisphosphonate medication zoledronic acid. METHODS: A 61-year-old woman
      with known bull's eye chloroquine maculopathy presented with sudden decrease in
      vision within 1 week of receiving intravenous zoledronic acid (Aclasta). Complete
      ophthalmic examination including fundus photography, autofluorescence, optical
      coherence tomography, and visual field testing were performed over 11/2 years of
      follow-up. RESULTS: Decreased visual acuity, central visual field depression, and
      loss of the outer retinal layers on optical coherence tomography were seen in the
      symptomatic eye. The patient's last dose of chloroquine was over 15 years ago,
      with stable visual acuity and visual fields over this period, making chloroquine
      maculopathy an unlikely cause for the acute visual decline. The temporal
      association with the administration of intravenous zoledronic acid suggests a
      causative role for this mediation. CONCLUSION: Exposure to zoledronic acid seems
      to have precipitated acute visual loss in an eye with known chloroquine toxicity
      after 15 years of quiescence. Retinal toxicity may represent a rare adverse
      reaction to zoledronic acid, but this case suggests that caution should be used
      when administering this medication to patients with compromised retinal
      integrity.

PMID- 25372539
TI  - Choroidal neovascularization secondary to cuticular drusen treated with
      intravitreal bevacizumab.
AB  - PURPOSE: To report our experience with intravitreal injection of bevacizumab in
      the treatment of cuticular drusen-associated choroidal neovascularization.
      METHODS: An interventional case report. A 38-year-old woman presented with
      decreased visual acuity in her right eye and cuticular drusen-associated
      choroidal neovascularization. RESULTS: Prolonged (12 months) remission of
      choroidal neovascularization after 3 monthly bevacizumab injections with
      improvement in visual acuity from 20/120 to 20/20. CONCLUSION: The use of
      antivascular endothelial growth factor in the management of cuticular drusen
      associated choroidal neovascularization seems to be an effective method of
      treatment showing both resolution of optical coherence tomography changes and
      improvement in visual acuity in this case. However, further studies with bigger
      sample size and longer follow-up are required to confirm the findings.

PMID- 25372540
TI  - Reversible vision loss and outer retinal abnormalities after intravitreal
      ocriplasmin injection.
AB  - PURPOSE: Ocriplasmin is a truncated form of the human serine protease plasmin,
      which was recently approved for the nonsurgical treatment of symptomatic
      vitreomacular adhesions. According to its FDA label, approximately 8% of subjects
      experienced acute transient vision loss during the first week after injection
      with no alternative explanation for the change. This report focuses on a recent
      case of recovered vision loss over a 3-month period after the injection. METHODS:
      A comprehensive ophthalmic examination was performed before the injection, during
      the day of the injection, and at 2 days, 2 weeks, 1 month, and 4 months after the
      injection. This examination included a full ophthalmic workup and imaging with
      spectral domain optical coherence tomography. A case of a 55-year-old woman who
      experienced acute severe vision loss 2 days after the treatment with ocriplasmin
      was reported. RESULTS: Distinct alterations, as seen with spectral domain optical
      coherence tomography, were observed in the ellipsoid zone of photoreceptors.
      These changes together with patient's visual acuity gradually recovered over a 3
      month period after the injection. CONCLUSION: Further investigation may be
      warranted to fully elucidate the precise molecular mechanisms involved in
      patients with unexplained vision loss after ocriplasmin injection.

PMID- 25372541
TI  - Retinal infiltrates secondary to metastatic squamous cell carcinoma masquerading
      as infectious retinitis.
AB  - PURPOSE: This report presents a case of metastatic carcinoma to the retina.
      METHODS: Retrospective chart review and systematic literature review. The patient
      was a 78-year-old man with history of small-cell lung cancer and with the
      development of metastatic carcinoma to the retina. RESULTS: The review of this
      case and previous literature reveals that the presentation of retinal metastases
      can occasionally be misinterpreted as infectious retinitis, which can delay the
      diagnosis of the disease. CONCLUSION: Metastatic carcinoma to the retina is a
      rare condition, which should be considered in patients who are suspected of
      having infectious retinopathy and who fail to respond to traditional
      antimicrobial therapies.

PMID- 25372542
TI  - Intraretinal fibrosis in exudative diabetic macular edema after ranibizumab
      treatments.
AB  - PURPOSE: To describe the clinical and optical coherence tomography findings of an
      eye with diabetic macular edema that developed intraretinal fibrosis in an area
      previously occupied by lipid accumulating after the intravitreous ranibizumab
      treatment. METHODS: Interventional case report. RESULTS: An 85-year-old man
      presented with diabetic macular edema involving the center of the macula with a
      half disk area of lipid inferotemporal to the macula. He received ranibizumab
      treatments after the principles of the Diabetic Retinopathy Clinical Research
      Network retreatment guidelines. After 12 doses of intravitreous ranibizumab
      injections over 20 months, macular edema resolved, visual acuity improved from
      20/63 to 20/40, and the central subfield thickness decreased from 404 MUm to 234
      MUm. As the edema resolved, the area of lipid did not expand toward the fovea but
      was replaced by fibrosis occupying the area of lipid, only smaller in extent.
      Optical coherence tomography scans showed an intraretinal, dome-shaped
      hyperreflective area corresponding to the fibrosis. CONCLUSION: This case report,
      to our knowledge, provides the first documentation of intraretinal fibrosis
      replacing an area of lipid associated with diabetic macular edema after anti
      vascular endothelial growth factor therapy, as had been described previously
      following laser photocoagulation for diabetic macular edema. Unlike some previous
      reports of lipid accumulating within the fovea with subsequent fibrosis
      corresponding to the metaplastic retinal pigment epithelium on histopathology,
      with or without laser treatment, the lipid in this case did not expand into the
      fovea before the development of fibrosis, and optical coherence tomography
      confirmed that the fibrosis was located in the intraretinal rather than the
      subretinal pigment epithelium space.

PMID- 25372543
TI  - Exudative retinal detachment as a presenting sign in Philadelphia chromosome
      positive acute lymphoblastic leukemia.
AB  - PURPOSE: We present here a case of bilateral exudative retinal detachments in a
      patient with Philadelphia chromosome-positive acute lymphoblastic leukemia and
      describe the patient's response to induction chemotherapy and clinical course.
      METHODS: A retrospective case study with fundus photographs and optical coherence
      tomography. A 46-year-old woman presented with bilateral exudative retinal
      detachments. A systemic evaluation revealed acute lymphoblastic leukemia. RESULTS
      AND CONCLUSION: This is an exceptional case in that the exudative retinal change
      so closely parallels systemic response to remission and relapse in a hematologic
      malignancy, and suggests that the clinical course of exudative retinal change may
      be a legitimate proxy for efficacy-or failure-of systemic therapy.

PMID- 25372544
TI  - Anti-vascular endothelial growth factor injection technique for recurrent
      exudative macular degeneration in a telescope-implanted eye.
AB  - PURPOSE: To describe the management of a patient with neovascular age-related
      macular degeneration and an implantable miniature telescope. METHODS: Clinical
      case report. RESULTS: The patient developed recurrent choroidal
      neovascularization after telescope implantation and was successfully managed with
      a series of anti-vascular endothelial growth factor injections and serial ocular
      coherence tomography through the telescope. CONCLUSION: Intravitreal injections
      can be safely performed in an eye with a telescope using standard ocular
      coherence tomography imaging and taking into consideration the unique geometric
      dimensions of the telescope.

PMID- 25372545
TI  - Central retinal artery occlusion occurring intraoperatively during angiography
      for subarachnoid hemorrhage: a case report.
AB  - PURPOSE: To report a case of central retinal artery occlusion that occurred
      during cerebral angiography for the treatment of vasospasm secondary to
      subarachnoid hemorrhage. RESULTS: Examination was notable for 20/Hand Motion
      vision and an afferent pupillary defect. Fundus examination at the time of the
      event revealed a cherry red spot typical of central retinal artery occlusion with
      surrounding edema of the retina and severe attenuation of the arterioles. There
      were no emboli noted. Review of the angiography confirmed flow to the ophthalmic
      artery and retina at the start of the procedure, with severely decreased flow
      noted at the end of the procedure. Five days after presentation, there were
      notable areas of potential choroidal infarction, indicating that the ophthalmic
      artery was also involved to some extent. The patient refused fluorescein
      angiography, which could have provided more insight to the extent of ischemia.
      Optical coherence tomography also showed diffuse retinal edema. She was monitored
      for complications resulting from this event with visual acuity remaining largely
      unchanged. CONCLUSION: Ophthalmic and central retinal artery occlusions are
      devastating events that result in severe vision loss. Most patients have some
      underlying risk factors precluding the initial event. Undergoing angiography, or
      other invasive vascular procedure, may put the patient at risk for distal
      vascular occlusions. Our case is unique in that it shows intraoperative imaging
      of the acute event occurrence.

PMID- 25372546
TI  - Resolution of bilateral cystoid macular edema and subfoveal serous retinal
      detachments after treatment with bortezomib in a patient with "smoldering"
      multiple myeloma.
AB  - PURPOSE: To describe a case of a patient with multiple myeloma without
      extraocular end-organ damage but with cystoid macular edema and macular
      detachments who was treated with bortezomib and dexamethasone. There was a
      complete resolution of retinal and subretinal fluid and significant improvement
      of vision. METHODS: The patient's ocular disease was monitored with visual
      acuity, dilated fundus examinations, and optical coherence tomography before,
      during, and after treatment. The patient in this case report was a 43-year-old
      African American man with a medical history of untreated, "smoldering" multiple
      myeloma, hypertension, hyperlipidemia who presented to our clinic with
      progressive painless loss of vision in both eyes over 6 weeks. RESULTS: Before
      treatment with bortezomib and dexamethasone, the patient had complaints of
      confusion, muscle stiffness, joint pain, and 20-lb unintentional weight loss;
      however, he did not have hypercalcemia, renal insufficiency, anemia, or bone
      lesions typical of active multiple myeloma. The bilateral cystoid macular edema
      and subfoveal neurosensory retinal detachments, noted on presentation and
      confirmed by optical coherence tomography, completely resolved over the course of
      treatment with bortezomib and dexamethasone. CONCLUSION: This case of bilateral
      cystoid macular edema and subfoveal neurosensory retinal detachments is
      remarkable for both its presentation and response to therapy. The macular edema
      and macular detachments along with nonspecific complaints of confusion, muscle
      stiffness, joint pain, and weight loss were the presenting signs and symptoms;
      signs typically used as guides to initiate treatment for multiple myeloma were
      not present. Macular edema in the context of paraproteinemia is usually
      associated with Waldenstrom's macroglobulinemia and has classically been reported
      as "silent" with respect to fluorescein angiography. Our patient has multiple
      myeloma and demonstrated leakage on fluorescein angiography. The case is also
      notable in that there was improvement in visual acuity and restoration of normal
      macular anatomy after receiving eight cycles of bortezomib and dexamethasone.
      Bortezomib, a chemotherapeutic agent used to treat refractory or rapidly
      advancing multiple myeloma, had been used previously to treat similar maculopathy
      in Waldenstrom disease along with plasmapheresis with resolution of macular edema
      and improvement in visual acuity. Our patient with multiple myeloma did not
      require plasmapheresis for significant clinical improvement. Treatment with
      bortezomib and dexamethasone alone was sufficient to clear the bilateral cystoid
      macular edema and subretinal fluid.

PMID- 25372547
TI  - Nanoscale surface potential variation correlates with local S/Se ratio in
      solution-processed CZTSSe solar cells.
AB  - Thin film solar cells made from Cu, Zn, Sn, and S/Se can be processed from
      solution to yield high-performing kesterite (CZTS or CZTSSe) photovoltaics. We
      present a microstructural study of solution-deposited CZTSSe films prepared by
      nanocrystal-based ink approaches using scanning probe microscopy (SPM) and
      scanning electron microscopy (SEM) coupled with energy dispersive X-ray
      spectroscopy (EDS). We correlate scanning Kelvin probe microscopy (SKPM) maps of
      local surface potential with SEM/EDS images of the exact same regions of the
      film, allowing us to relate observed variations in surface potential to local
      variations in stoichiometry. Specifically, we find a correlation between surface
      potential and the S/(S + Se) composition ratio. In particular, we find that
      regions with high S/(S + Se) ratios are often associated with regions of more
      negative surface potential and thus higher work function. The change in work
      function is larger than the expected change in the valence band position with
      these small changes in sulfur, and thus the data suggest an increase in acceptor
      like defects with increasing sulfur. These findings provide new experimental
      insight into the microscopic relationships between composition, structure, and
      electronic properties in these promising photovoltaic materials. 

PMID- 25372549
TI  - A liquid azobenzene derivative as a solvent-free solar thermal fuel.
AB  - A liquid solar thermal fuel is developed; a low-molecular weight liquid trans
      azobenzene derivative shows facile photoisomerization to the higher-energy cis
      isomer in neat condition so that a high volumetric energy density is achieved.
      Shear viscosity measurements for each isomer liquid unveiled transitions from non
      Newtonian to Newtonian fluids. 

PMID- 25372548
TI  - A novel missense mutation in ADAMTS10 in Norwegian Elkhound primary glaucoma.
AB  - Primary glaucoma is one of the most common causes of irreversible blindness both
      in humans and in dogs. Glaucoma is an optic neuropathy affecting the retinal
      ganglion cells and optic nerve, and elevated intraocular pressure is commonly
      associated with the disease. Glaucoma is broadly classified into primary open
      angle (POAG), primary closed angle (PCAG) and primary congenital glaucoma (PCG).
      Human glaucomas are genetically heterogeneous and multiple loci have been
      identified. Glaucoma affects several dog breeds but only three loci and one gene
      have been implicated so far. We have investigated the genetics of primary
      glaucoma in the Norwegian Elkhound (NE). We established a small pedigree around
      the affected NEs collected from Finland, US and UK and performed a genome-wide
      association study with 9 cases and 8 controls to map the glaucoma gene to 750 kb
      region on canine chromosome 20 (praw = 4.93*10-6, pgenome = 0.025). The
      associated region contains a previously identified glaucoma gene, ADAMTS10, which
      was subjected to mutation screening in the coding regions. A fully segregating
      missense mutation (p.A387T) in exon 9 was found in 14 cases and 572 unaffected
      NEs (pFisher = 3.5*10-27) with a high carrier frequency (25.3%). The mutation
      interrupts a highly conserved residue in the metalloprotease domain of ADAMTS10,
      likely affecting its functional capacity. Our study identifies the genetic cause
      of primary glaucoma in NEs and enables the development of a genetic test for
      breeding purposes. This study establishes also a new spontaneous canine model for
      glaucoma research to study the ADAMTS10 biology in optical neuropathy. 

PMID- 25372550
TI  - "It Doesn't All Just Stop at 18": Psychological Adjustment and Support Needs of
      Adults Born With Cleft Lip and/or Palate.
AB  - BACKGROUND: Cleft in the lip and/or the palate (CL/P) is considered to be a
      lifelong condition, yet relatively little is known about the long-term outcomes
      for patients. Existing literature is largely outdated and conflicted, with an
      almost exclusive focus on medical aspects and deficits. OBJECTIVE: To explore the
      psychological adjustment and possible support needs of a large number of adults
      born with CL/P from their own perspective. DESIGN: Fifty-two individual telephone
      interviews eliciting qualitative data. RESULTS: Qualitative analysis identified
      five themes. Participants reported a range of challenges in relation to discharge
      from the service, additional surgery as an adult, social and romantic
      relationships, higher education, vocational achievement, and access to
      psychological support. The findings imply that most adults with a cleft adjust
      well to these challenges and report many positive outcomes. For a minority of
      patients, issues attributed to the cleft may continue to cause distress in
      adulthood. CONCLUSIONS: Adults with CL/P may require psychological support,
      information about the heritability of cleft, signposting and referrals from
      nonspecialists, support regarding further treatment, and opportunities to take
      part in research and activities. New issues arising in adulthood, such as
      entering the workplace, forming long-term relationships, and starting a family,
      may warrant both further investigation and additional support. Further work is
      needed to identify the factors that contribute to psychological distress and
      resilience, as well as the timing of particular points of risk and opportunity
      for personal growth.

PMID- 25372551
TI  - Bovine Cartilage: A Near Perfect Training Tool for Carving Ear Cartilage
      Framework.
AB  - OBJECTIVE: To develop a training module for carving ear cartilage. SETTING:
      Designing the ear framework is one of the most challenging surgical steps during
      ear reconstruction in microtia and acquired deformities of the ear. Trainees do
      not get an opportunity to carve ear cartilage during their training period.
      MATERIAL: Ox scapular cartilage was retrieved from a manual slaughterhouse. It
      was transported in a 4 degrees C ice chamber. This was used as a training
      material for carving the ear framework. Each scapular cartilage was adequate for
      two to three ear frameworks. RESULTS: Twenty-two trainees used the bovine
      cartilage in a wet lab. All had positive feedback on their ear framework carving
      experience. In their opinion, the consistency, flexibility, and cutting
      experience almost matched that of human costal cartilage. CONCLUSION: The ox
      scapular cartilage has been found to be a near perfect material for training and
      practicing carving of the ear cartilage.

PMID- 25372552
TI  - Bridging the Gap: Sella Turcica in Unilateral Cleft Lip and Palate Patients.
AB  - Objectives :  The aims of this study were to analyze the prevalence of sella
      turcica bridging and to measure the size of the sella turcica on profile
      cephalograms in a homogenous group of surgically repaired unilateral cleft lip
      and palate (UCLP) patients. Setting :  Tertiary care center. Design : 
      Retrospective cross-sectional study. Patients :  Preorthodontic lateral
      cephalometric radiographs of 64 UCLP individuals between the ages of 16 and 29
      years along with an equal number of age- and sex-matched skeletal Class I
      controls. Main Outcome Measures :  The extent of calcification of the
      interclinoid ligament was quantified (completely calcified, partially calcified,
      no calcification) and mean values compared. Length, depth, and diameter of the
      sella turcica were also measured. The results were statistically analyzed using
      paired t test and Wilcoxon signed ranks test. Results :  Complete sella bridging
      of both type A (4.6%) and type B (21.7%) was significantly higher in UCLP
      patients. This has not been reported previously. Partial sella bridging was also
      higher in cleft patients as evaluated by two methods (42.18%, 39.06%). This study
      demonstrated a statistically significant decrease in all dimensions of sella
      turcica in UCLP patients. Conclusions :  The UCLP patients apparently had higher
      predilection for sella turcica bridging. The dimensions of sella turcica were
      also seen to be significantly smaller than the control group. Defective
      proliferation and deviated pathways of neural crest cell migration as well as
      premature rupture of contact between neuroepithelium and oral ectoderm as
      postulated causes are discussed.

PMID- 25372553
TI  - Screening of Transforming Growth Factor Beta 3 and Jagged2 Genes in the Malay
      Population With Nonsyndromic Cleft Lip With or Without Cleft Palate.
AB  - OBJECTIVE:   To determine the prevalence of mutations in transforming growth
      factor beta 3 (TGFbeta3) and Jagged2 genes and their association with
      nonsyndromic cleft lip with or without cleft palate (CL+/-P) patients. DESIGN:  
      Cross-sectional study on nonsyndromic CL+/-P and noncleft patients. SETTING:  
      Reconstructive clinic and outpatient dental clinic, Hospital Universiti Sains,
      Malaysia. PATIENTS:   Blood samples of 96 nonsyndromic CL+/-P and 96 noncleft
      subjects. MAIN OUTCOME MEASURE:   Prevalence and association of mutations in
      TGFbeta3 and Jagged2 genes with nonsyndromic CL+/-P. RESULTS:   Most of the
      nonsyndromic CL+/-P patients (53.1%) had left unilateral CLP. There were slightly
      more females (56.6%) compared with males. The prevalence of the mutations in the
      TGFbeta3 gene was 17.7 (95% confidence interval [CI]: 9.5, 24.5) and in the
      Jagged2 gene was 12.5% (95% CI: 5.5, 18.5), which was higher compared with the
      noncleft group. For the TGFbeta3 gene, there was no mutation in the coding region
      in either of the groups. All variants were single nucleotide polymorphisms
      located within the intronic flanking region. Two variants were identified
      (g.15812T>G and g.15966A>G) in both nonsyndromic CL+/-P and noncleft patients.
      However, the association was not significant (P > .05). Three variants
      (g.19779C>T, g.19547G>A, and g.19712C>T) were identified in the Jagged2 gene
      among nonsyndromic CL+/-P and noncleft patients. Only g.19712C>T showed a
      significant association with nonsyndromic CL+/-P patients (P = .039). CONCLUSION:
      g.19712C>T might play a crucial role in the development of cleft lip and
      palate. To the best of our knowledge, this is the first report of the mutation
      found within intron 13 of the Jagged2 gene among nonsyndromic CL+/-P Malay
      patients.

PMID- 25372555
TI  - Insights from ERPs into attention during recovery after cerebellar stroke: a case
      report.
AB  - The role of the cerebellum in cognitive performance and attentional processes is
      a focus of research in recent years. We investigated the P300 component in a
      patient with a left posterior cerebellar ischemic stroke during both the acute
      phase and over 4 weeks of follow-up. After stroke, auditory event-related
      potentials showed a reduction in P3 amplitude, which appears to improve instead
      after 4 weeks of follow-up. These event-related potential findings could suggest
      a specific neural pattern of disruption in selective attention during the
      discrimination processes of the stimulus following a posterior cerebellar lesion.
      A recovery is observed in the long term. 

PMID- 25372558
TI  - Antidepressant use in pregnancy: an evaluation of adverse outcomes excluding
      malformation.
AB  - BACKGROUND: To date, many studies have been published regarding the safety of
      antidepressant use in pregnancy. However, most have been regarding a possible
      association with major malformations and there have been relatively few studies
      that have examined other infant outcomes specifically. OBJECTIVE: To evaluate
      possible adverse effects of antidepressant use in pregnancy. METHODS: We searched
      the literature, using Medline, PUBMED, Embase, and Reprotox , and retrieved key
      articles and reviews of the topic.We examined all outcomes with the exception of
      major/minor malformations. RESULTS: We did not find an overall increased risk
      associated with lower mean birthweight, small for gestational age or long-term
      neurodevelopmental adverse outcomes. However, there does appear to be a
      significantly increased risk for spontaneous abortion, preterm birth and low
      birthweight less than 2,500 gm. In addition, a possible increased risk for
      Persistent Pulmonary Hypertension of the Newborn (PPHN) and evidence of Poor
      Neonatal Adaptation Syndrome (PNAS) following use in late pregnancy. All of the
      observed risks were of a very low magnitude and the clinical significance of
      these results is unknown. CONCLUSIONS: This information should not preclude a
      pregnant women from being treated for depression if required, as untreated
      depression is also associated with adverse effects on the infant.However, further
      research needs to be conducted where it is possible to control for maternal
      depression, in order to evaluate whether these adverse events are due to the
      underlying maternal illness, the antidepressant, or possibly a combination of
      both.

PMID- 25372557
TI  - Gender differences in the psychopathology of emerging psychosis.
AB  - BACKGROUND: Gender differences have often been found in psychopathological
      symptoms among chronic schizophrenia and first-episode psychosis (FEP) patients.
      However, many of these studies suffer from methodological problems and show
      inconsistent results. Furthermore, very few studies have investigated gender
      differences in individuals with an at-risk mental state (ARMS) for psychosis.
      METHODS: Psychopathological symptoms were assessed in 117 ARMS and 87 FEP
      patients by two observer-rated scales, namely, the expanded version of the Brief
      Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative
      Symptoms (SANS), and by one self-report scale, the Frankfurt Complaint
      Questionnaire (FCQ). Gender differences were investigated by applying Analyses of
      Variance using the BPRS, SANS and FCQ subscales as dependent variables, and group
      and sex as between-subject factors - in a second step by including age,
      antipsychotic, antidepressant and cannabis use as covariates. RESULTS: There were
      no significant gender * patient group interactions, suggesting that gender
      effects did not differ between patient groups. Women had higher scores in
      positive psychotic symptoms (BPRS Psychosis/ Thought Disturbance) while men had
      higher scores in negative symptoms (BPRS negative symptoms, SANS total score, as
      well as subscales Affective Flattening, Avolition-Apathy and Asociality
      Anhedonia). However, the differences did not withstand correction for multiple
      testing. The results did not change when corrected for potential confounders.
      CONCLUSIONS: There do not seem to be any gender differences in psychopathology,
      neither in ARMS nor in FEP patients, as regards self-reported or observerrated
      symptoms, when corrected for multiple testing and potential confounders.

PMID- 25372556
TI  - Effects of vitamin E from supplements and diet on colonic alpha- and gamma
      tocopherol concentrations in persons at increased colon cancer risk.
AB  - The available evidence indicates that gamma-tocopherol has more potential for
      colon cancer prevention than alpha-tocopherol, but little is known about the
      effects of foods and supplements on tocopherol levels in human colon. This study
      randomized 120 subjects at increased colon cancer risk to either a Mediterranean
      or a Healthy Eating diet for 6 mo. Supplement use was reported by 39% of the
      subjects, and vitamin E intake from supplements was twofold higher than that from
      foods. Serum alpha-tocopherol at baseline was positively predicted by dietary
      intakes of synthetic vitamin E in foods and supplements but not by natural alpha
      tocopherol from foods. For serum gamma-tocopherol, dietary gamma-tocopherol was
      not a predictor, but dietary alpha-tocopherol was a negative predictor. Unlike
      with serum, the data supported a role for metabolic factors, and not a direct
      effect of diet, in governing concentrations of both alpha- and gamma-tocopherol
      in colon. The Mediterranean intervention increased intakes of natural alpha
      tocopherol, which is high in nuts, and decreased intakes of gamma-tocopherol,
      which is low in olive oil. These dietary changes had no significant effects on
      colon tocopherols. The impact of diet on colon tocopherols therefore appears to
      be limited. 

PMID- 25372559
TI  - Maternal depression and perception of teratogenic risk.
AB  - Depression in pregnancy is characterized by unrealistically heightened perception
      of teratogenic risk. Appropriate counseling regarding the exposure at hand can
      assist in reducing maternal concerns. Addressing depression during pregnancy and,
      in parallel, providing evidence based counseling and reassurance regarding
      different antidepressants in pregnancy may avert major health risks.

PMID- 25372560
TI  - The impact of maternal positive and negative affect on fetal physiology and
      diurnal patterns.
AB  - BACKGROUND: While research has shown that maternal mood (depression and/or
      anxiety) can have effects on the fetus, little is known about whether maternal
      positive and negative affect influences the fetus. METHOD: We examined fetal
      vascular and heart rate changes at 36 weeks gestation in 53 euthymic mothers
      according to their Positive and Negative Affect Scale (PANAS) scores. RESULTS:
      Mothers who reported high levels of negative affect showed reduced uterine artery
      flow, decreased fetal heart rate (fHR) variability, an altered diurnal pattern,
      and decreased uterine artery cross-sectional area compared to mothers who
      reported low levels of negative affect. Mothers with low positive affect had a
      steeper diurnal pattern in fHR accelerations and decreased uterine artery mean
      velocity flow than mothers with high positive affect. LIMITATIONS: Our
      observational study suffers from a small sample size. CONCLUSION: Even in the
      absence of an Axis I Major Depressive Disorder (MDD), variations in maternal
      affect appear to be associated with variations in fetal and uterine physiology.

PMID- 25372561
TI  - Gender differences in the prevalence and correlates of psychotropic medication
      use among older adults in Israel.
AB  - BACKGROUND: This study evaluates gender differences in the prevalence of
      psychotropic medications use among elderly Israelis and the socio-demographic,
      physical and mental health correlates of their use. METHOD: Data were taken from
      a national survey that sampled the community-dwelling Jewish population aged 65
      94 in Israel. Psychotropic medications were assessed from the list of all
      medications recorded during a faceto- face interview. The current analysis
      focused on three medication groups: anxiolytics, sedatives/hypnotics and
      antidepressants. RESULTS: A significantly higher use of anxiolytics was observed
      among women compared to men after taking into account their worse physical and
      mental health. Age, not being married, sleeping problems and depressive symptoms
      were significant correlates among men while number of non-psychotropic
      medications, any life trauma and being married correlated with use of anxiolytics
      and sedatives/hypnotics among women. The use of antidepressants was low in men
      and women and was related mainly to disability in ADL. CONCLUSIONS: This study
      points to possibly overprescribing of anxiolytics among women and low detection
      and treatment of depression among the elderly in general.

PMID- 25372562
TI  - Postpartum anxiety in a cohort of women from the general population: risk factors
      and association with depression during last week of pregnancy, postpartum
      depression and postpartum PTSD.
AB  - BACKGROUND: In contrast to postpartum depression, postpartum anxiety receives
      less attention, especially in the general population. Acknowledging the
      phenomenon is important, as it may lead to significant distress and impair
      maternal functioning. OBJECTIVES: To explore the phenomenon in a cohort of women
      in the general population and to investigate possible associated factors.
      METHODS: Within the first days after childbirth, women at Chaim Sheba Medical
      Center maternity ward were interviewed. Questionnaires included psychosocial
      variables, feelings and fears during pregnancy and childbirth, and the Edinburgh
      Postnatal Depression Scale (EPDS) (referring to the last week before delivery). A
      month later, subjects completed the EPDS, a modified Spielberger Anxiety Scale
      and the Posttraumatic Stress Diagnostic Scale via telephone. RESULTS: 40.4% had
      high anxiety scores. A significant association was noted between postpartum
      anxiety and depression during the last week of pregnancy, postpartum depression,
      as well as postpartum PTSD. Anxiety scores were almost 50% higher in those who
      suffered from postpartum PTSD compared to those who experienced postpartum
      depression. Associations were also found with fear of the birth, fear of death
      during delivery (mother and fetus), feeling lack of control during labor and less
      confidence in self and medical staff. Of women who developed postpartum anxiety,
      75% reported feeling anger, fear or emotional detachment during childbirth. No
      association was found with birth complications. CONCLUSIONS: Anxiety
      symptomatology appears to be a common manifestation after childbirth. It is
      therefore important to inquire about depression and fears during pregnancy and
      childbirth and subjective experience in order to anticipate postpartum anxiety
      symptoms, even by means of a brief screening test. The finding that postpartum
      PTSD was associated with the severity of postpartum anxiety may be used in the
      future as a potential identifier of PTSD symptoms in women with high anxiety
      scores.

PMID- 25372563
TI  - Aripiprazole combined with other psychotropic drugs in pregnancy: two case
      reports.
AB  - Maternal exposure to second generation antipsychotics during pregnancy has been
      associated with some negative effects for both mothers and infants. Aripiprazole
      is becoming more readily used, although data regarding its use in pregnancy are
      limited. Additionally there are limited data with regards to the impact of
      polypharmacy on pregnancy outcomes. Given the relative paucity of information
      related to aripiprazole use in pregnancy it is difficult to counsel women on
      potential risks or side effects. We present two cases that illustrate the use of
      aripiprazole as a part of a polypharmacy regimen in pregnancy and describe the
      pregnancy outcomes in an effort to help clinicians facing complex treatment
      decisions in pregnancy. 

PMID- 25372564
TI  - Gender and disordered eating of adolescents in Israel.
AB  - BACKGROUND: Studies from recent decades indicate that the ideal of thinness can
      be discerned in a growing dissatisfaction with weight and an increase of the
      prevalence of disordered eating at an earlier age of onset. OBJECTIVE: The
      purpose of this study is to evaluate the prevalence of disordered eating (above
      the cutoff point of 30 on the EAT-40) among a normal population of school
      students in Israel. METHODS: The study sample was composed of Israeli (Jewish)
      adolescents in grades 7 to 12 from four schools. Of 326 students approached (181
      females and 142 males), 323 completed the self-report EAT-40 and a structured
      questionnaire that provided socio-demographic and other information. RESULTS:
      41.5% of adolescents were not satisfied with their weight and 45.3% want to lose
      weight. A third of the sample engages in dieting behavior frequently; 6.1% of the
      adolescents have pathologic EAT-40 scores, with about three times as many girls
      as boys exhibiting disordered eating; 8.2% of the girls and 2.8% of the males
      show disordered eating (O=0.115, p <0.05). Among adolescents who are dissatisfied
      with their weight there are 7.6 times more with pathologic EAT scores than those
      who are satisfied with their weight (O=0.220; p <0.01). There are 10.8 times more
      pathologic EAT scores among adolescents who wish to lose weight than among those
      who do not wish to reduce their weight (O=0.237; p <0.01). No significant
      differences in pathologic EAT scores were found among adolescents from different
      ethnic backgrounds or levels of religious observance. CONCLUSION: The prevalence
      of disordered eating among adolescents in Israel is higher than other countries
      in general, and among males in particular. There is a need for increased efforts
      to detect adolescents at risk for developing eating disorders, with the
      assistance of clinical tools. In addition an educational policy for disordered
      eating prevention should be instituted.

PMID- 25372565
TI  - Disordered eating and cultural distinctions: exploring prevalence and predictors
      among women in Israel.
AB  - BACKGROUND: Cultural differences in serious eating problems among adult women
      have important treatment and prevention implications yet remain relatively
      unexplored. This is the first study to examine these issues among Israel's multi
      cultural adult population. METHOD: Disordered eating behaviors (DEB) are assessed
      with 14 DSM-related symptoms (including binge eating) in a multi-cultural sample
      of 485 women. Prevalence rates and clinical predictors of DEB severity are
      examined for three culturally distinct groups of Jews. RESULTS: Second generation
      Israeli-born and first generation Israelis of Sephardic and Ashkenazi origins
      differ significantly in DEB prevalence (19.4%, 11.4%, 13.9%, p<.05). Regarding
      clinical predictors, self-criticism is strongest predictor for second generation
      while weight is strongest predictor for both first generation groups.
      CONCLUSIONS: Prevailing wisdom largely attributes eating disturbances to cultural
      thinness norms. However, substantial differences between culturally distinct
      groups of Israeli Jews, similarly exposed to westernized norms, challenge the
      prevailing wisdom. Culturally sensitive interventions warrant additional research
      and more illuminating explanatory models than "one size fits all."

PMID- 25372566
TI  - Using molecular tools to decipher the complex world of plant resistance inducers:
      an apple case study.
AB  - Exogenous application of plant resistance inducers (PRIs) able to activate plant
      defenses is an interesting approach for new integrated pest management practices.
      The full integration of PRIs into agricultural practices requires methods for the
      fast and objective upstream screening of efficient PRIs and optimization of their
      application. To select active PRIs, we used a molecular tool as an alternative to
      methods involving plant protection assays. The expressions of 28 genes involved
      in complementary plant defense mechanisms were simultaneously determined by
      quantitative real-time PCR in PRI-treated tissues. Using a set of 10 commercial
      preparations and considering the pathosystem apple/Erwinia amylovora, this study
      shows a strong correlation between defense activation and protection efficiency
      in controlled conditions, thus enabling the easy identification of promising PRIs
      in fire blight protection. Hence this work clearly highlights the benefits of
      using a molecular tool to discriminate nonactive PRI preparations and provides
      useful molecular markers for the optimization of their use in orchard. 

PMID- 25372567
TI  - HemI: a toolkit for illustrating heatmaps.
AB  - Recent high-throughput techniques have generated a flood of biological data in
      all aspects. The transformation and visualization of multi-dimensional and
      numerical gene or protein expression data in a single heatmap can provide a
      concise but comprehensive presentation of molecular dynamics under different
      conditions. In this work, we developed an easy-to-use tool named HemI (Heat map
      Illustrator), which can visualize either gene or protein expression data in
      heatmaps. Additionally, the heatmaps can be recolored, rescaled or rotated in a
      customized manner. In addition, HemI provides multiple clustering strategies for
      analyzing the data. Publication-quality figures can be exported directly. We
      propose that HemI can be a useful toolkit for conveniently visualizing and
      manipulating heatmaps. The stand-alone packages of HemI were implemented in Java
      and can be accessed at http://hemi.biocuckoo.org/down.php. 

PMID- 25372568
TI  - Breast cancer following ovarian cancer in BRCA mutation carriers.
AB  - IMPORTANCE: BRCA mutation carriers are at increased risk of developing breast
      cancer. However, the incidence of breast cancer after a diagnosis of epithelial
      ovarian cancer (EOC), one of the tubal/peritoneal cancers collectively referred
      to as pelvic serous carcinomas, is not well known. Optimal breast cancer
      surveillance and detection for these patients have also not been well
      characterized. OBJECTIVES: To determine the incidence of breast cancer after a
      diagnosis of EOC and to evaluate the need for breast cancer surveillance for
      these patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective database
      review of 364 patients who underwent BRCA mutation testing for EOC (stages I-IV)
      between 1998 and 2012 at an academic medical center with gynecologic and breast
      cancer centers. MAIN OUTCOMES AND MEASURES: Incidence of breast cancer and
      methods of surveillance. RESULTS: Of 364 patients, 135 (37.1%) were found to
      carry a germline BRCA1 or BRCA2 mutation. The mean age of patients at diagnosis
      of EOC was 49.5 years (range, 28-89 years). Of the 135 patients, 12 (8.9%)
      developed breast cancer. The median time from diagnosis of EOC to diagnosis of
      breast cancer was 50.5 months. Annual mammography was performed for 80 patients
      (59.3%), with annual magnetic resonance imaging of the breasts performed for 60
      patients (44.4%). Thirteen patients (9.6%) underwent a bilateral prophylactic
      mastectomy at a median of 23 months following EOC diagnosis. Breast cancer was
      most commonly diagnosed by mammography for 7 of the 12 patients (58.3%), 3
      (25.0%) of whom had a palpable mass and 2 (16.7%) of whom had incidental breast
      cancer detected during a prophylactic mastectomy. Seven patients with breast
      cancer (58.3%) underwent a bilateral mastectomy. All patients had early-stage
      breast cancer (stages 0-II). Four patients (33.3%) received adjuvant
      chemotherapy. At a median follow-up of 6.3 years, 4 of the 12 patients (33.3%)
      died of recurrent EOC after a diagnosis of breast cancer. The overall 10-year
      survival rate for the entire cohort of 135 patients was 17.0%. CONCLUSIONS AND
      RELEVANCE: The risk of metachronous breast cancer is low in patients with known
      BRCA mutations and EOC. A majority of these cases of breast cancer at an early
      stage are detected by use of mammography. Despite the small number of patients in
      our study, these results suggest that optimal breast cancer surveillance for
      patients with BRCA-associated EOC needs to be reevaluated given the low incidence
      of breast cancer among these high-risk patients. Confirmation of our findings
      from larger studies seems to be indicated.

PMID- 25372569
TI  - The very high premature mortality rate among active professional wrestlers is
      primarily due to cardiovascular disease.
AB  - PURPOSE: Recently, much media attention has been given to the premature deaths in
      professional wrestlers. Since no formal studies exist that have statistically
      examined the probability of premature mortality in professional wrestlers, we
      determined survival estimates for active wresters over the past quarter century
      to establish the factors contributing to the premature mortality of these
      individuals. METHODS: Data including cause of death was obtained from public
      records and wrestling publications in wrestlers who were active between January
      1, 1985 and December 31, 2011. 557 males were considered consistently active
      wrestlers during this time period. 2007 published mortality rates from the Center
      for Disease Control were used to compare the general population to the wrestlers
      by age, BMI, time period, and cause of death. Survival estimates and Cox hazard
      regression models were fit to determine incident premature deaths and factors
      associated with lower survival. Cumulative incidence function (CIF) estimates
      given years wrestled was obtained using a competing risks model for cause of
      death. RESULTS: The mortality for all wrestlers over the 26-year study period
      was.007 deaths/total person-years or 708 per 100,000 per year, and 16% of deaths
      occurred below age 50 years. Among wrestlers, the leading cause of deaths based
      on CIF was cardiovascular-related (38%). For cardiovascular-related deaths, drug
      overdose-related deaths and cancer deaths, wrestler mortality rates were
      respectively 15.1, 122.7 and 6.4 times greater than those of males in the general
      population. Survival estimates from hazard models indicated that BMI is
      significantly associated with the hazard of death from total time wrestling
      (p<0.0001). CONCLUSION: Professional wrestlers are more likely to die prematurely
      from cardiovascular disease compared to the general population and morbidly obese
      wrestlers are especially at risk. Results from this study may be useful for
      professional wrestlers, as well as wellness policy and medical care
      implementation.

PMID- 25372570
TI  - Health Care Indicators.
AB  - This regular feature of the journal includes a discussion of recent trends in
      health care delivery, employment, and prices. The statistics presented in this
      article are valuable in their own right for understanding the relationship
      between the health care sector and the overall economy. In addition, they allow
      us to anticipate the direction and magnitude of health care cost changes prior to
      the availability of more comprehensive data. Beginning with this issue, the
      article will include statistics not presented before on hospital operations and
      on the change in health care prices, with particular attention to the Medicare
      population.

PMID- 25372571
TI  - The relative impacts of climate and land-use change on conterminous United States
      bird species from 2001 to 2075.
AB  - Species distribution models often use climate data to assess contemporary and/or
      future ranges for animal or plant species. Land use and land cover (LULC) data
      are important predictor variables for determining species range, yet are rarely
      used when modeling future distributions. In this study, maximum entropy modeling
      was used to construct species distribution maps for 50 North American bird
      species to determine relative contributions of climate and LULC for contemporary
      (2001) and future (2075) time periods. Species presence data were used as a
      dependent variable, while climate, LULC, and topographic data were used as
      predictor variables. Results varied by species, but in general, measures of model
      fit for 2001 indicated significantly poorer fit when either climate or LULC data
      were excluded from model simulations. Climate covariates provided a higher
      contribution to 2001 model results than did LULC variables, although both
      categories of variables strongly contributed. The area deemed to be "suitable"
      for 2001 species presence was strongly affected by the choice of model
      covariates, with significantly larger ranges predicted when LULC was excluded as
      a covariate. Changes in species ranges for 2075 indicate much larger overall
      range changes due to projected climate change than due to projected LULC change.
      However, the choice of study area impacted results for both current and projected
      model applications, with truncation of actual species ranges resulting in lower
      model fit scores and increased difficulty in interpreting covariate impacts on
      species range. Results indicate species-specific response to climate and LULC
      variables; however, both climate and LULC variables clearly are important for
      modeling both contemporary and potential future species ranges. 

PMID- 25372572
TI  - Adjusting Performance Measures to Ensure Equitable Plan Comparisons.
AB  - When comparing health plans on scores from the Medicare Managed Care Consumer
      Assessment of Health Plans (MMC-CAHPS(r)) survey, the results should be adjusted
      for patient characteristics, not under the control of health plans, that might
      affect survey results. We developed an adjustment model that uses self-reported
      measures of health status, age, education, and whether someone helped the
      respondent with the questionnaire. The associations of health and education with
      survey responses differed by HCFA administrative region. Consequently, we
      recommend that the case-mix model include regional interactions. Analyses of the
      impact of adjustment show that the adjustments were usually small but not
      negligible.

PMID- 25372573
TI  - An electrically-stabilized liquid-crystalline phase: origin and application.
AB  - An azobenzene liquid-crystalline compound possessing two chiral centres at both
      peripheral ends of the molecular structure exhibits electric-field-induced
      birefringence in the isotropic liquid phase, which was found to be attributable
      to the stabilization of the liquid-crystalline organization by the emergence of
      the polar ferroelectric molecular ordering. The optically isotropic texture
      changes into the homogeneous birefringent texture by the application of the in
      plane electric field, which is a new type of switching mode applicable for the
      liquid crystal displays. The resulting birefringence can be erased by the
      irradiation of UV light, due to the photoinduced isomerization of the azobenzene
      compound, thus a dual controlled birefringent structure, by the irradiation of
      light and/or by the application of the electric field, is reported for the first
      time. 

PMID- 25372574
TI  - Health Care Indicators.
AB  - THIS REGULAR FEATURE OF THE JOURNAL INCLUDES A DISCUSSION OF EACH OF THE
      FOLLOWING FOUR TOPICS: community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25372575
TI  - "Just like talking to someone about like shit in your life and stuff, and they
      help you": Hopes and expectations for therapy among depressed adolescents.
AB  - OBJECTIVE: To explore hopes and expectations for therapy among a clinical
      population of depressed adolescents. METHOD: As part of a randomized clinical
      trial, 77 adolescents aged 11-17, with moderate to severe depression, were
      interviewed using a semi-structured interview schedule. The interviews were
      analysed qualitatively using framework analysis. RESULTS: The findings are
      reported around five themes: "the difficulty of imagining what will happen in
      therapy," "the 'talking cure,'" "the therapist as doctor," "therapy as a
      relationship," and "regaining the old self or developing new capacities."
      CONCLUSIONS: Differing expectations are likely to have implications for the way
      young people engage with treatment, and failure to identify these expectations
      may lead to a risk of treatment breakdown.

PMID- 25372576
TI  - Children's Use of Primary and Preventive Care Under Medicaid Managed Care.
AB  - The authors found that two mandatory Medicaid primary care case management (PCCM)
      programs were somewhat successful in improving access to primary care among
      children in the early 1990s. However, the Florida program, in which the PCCM
      benefit package included Early and Periodic Screening, Diagnostic, and Treatment
      (EPSDT) services, did not meaningfully increase EPSDT screening visits among
      preschoolers. Further, the increase seen in New Mexico, where EPSDT was carved
      out of the PCCM benefit package, was evident for both program participants and
      non-participants and therefore could not be attributed to the PCCM program.

PMID- 25372577
TI  - Diagnosis, treatment, and follow-up of medullary thyroid carcinoma:
      recommendations by the Thyroid Department of the Brazilian Society of
      Endocrinology and Metabolism.
AB  - INTRODUCTION: Medullary thyroid carcinoma (MTC) originates in the thyroid
      parafollicular cells and represents 3-4% of the malignant neoplasms that affect
      this gland. Approximately 25% of these cases are hereditary due to activating
      mutations in the REarranged during Transfection (RET) proto-oncogene. The course
      of MTC is indolent, and survival rates depend on the tumor stage at diagnosis.
      The present article describes clinical evidence-based guidelines for the
      diagnosis, treatment, and follow-up of MTC. OBJECTIVE: The aim of the consensus
      described herein, which was elaborated by Brazilian experts and sponsored by the
      Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was
      to discuss the diagnosis, treatment, and follow-up of individuals with MTC in
      accordance with the latest evidence reported in the literature. MATERIALS AND
      METHODS: After clinical questions were elaborated, the available literature was
      initially surveyed for evidence in the MedLine-PubMed database, followed by the
      Embase and Scientific Electronic Library Online/Latin American and Caribbean
      Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was
      assessed according to the Oxford classification of evidence levels, which is
      based on study design, and the best evidence available for each question was
      selected. RESULTS: Eleven questions corresponded to MTC diagnosis, 8 corresponded
      to its surgical treatment, and 13 corresponded to follow-up, for a total of 32
      recommendations. The present article discusses the clinical and molecular
      diagnosis, initial surgical treatment, and postoperative management of MTC, as
      well as the therapeutic options for metastatic disease. CONCLUSIONS: MTC should
      be suspected in individuals who present with thyroid nodules and family histories
      of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or
      typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid
      habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and
      anatomical-pathological examinations are useful for diagnostic confirmation.
      Surgery represents the only curative therapeutic strategy. The therapeutic
      options for metastatic disease remain limited and are restricted to disease
      control. Judicious postoperative assessments that focus on the identification of
      residual or recurrent disease are of paramount importance when defining the
      follow-up and later therapeutic management strategies.

PMID- 25372578
TI  - The role of imaging in congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is an autossomic recessive disorder caused
      by impaired steroidogenesis. Patients with CAH may present adrenal insufficiency
      with or without salt-wasting, as well as various degrees of virilization and
      fertility impairment, carrying a high incidence of testicular adrenal rest tumors
      and increased incidence of adrenal tumors. The diagnosis of CAH is made based on
      the adrenocortical profile hormonal evaluation and genotyping, in selected cases.
      Follow-up is mainly based on hormonal and clinical evaluation. Utility of imaging
      in this clinical setting may be helpful for the diagnosis, management, and follow
      up of the patients, although recommendations according to most guidelines are
      weak when present. Thus, the authors aimed to conduct a narrative synthesis of
      how imaging can help in the management of patients with CAH, especially focused
      on genitography, ultrasonography, computed tomography, and magnetic resonance
      imaging.

PMID- 25372579
TI  - Serum levels of retinol binding protein 4 in women with different levels of
      adiposity and glucose tolerance.
AB  - OBJECTIVE: Retinol-binding protein 4 (RBP4) is an adipokine responsible for
      vitamin A (retinol) transportation. Studies associated RBP4 increased levels with
      severity of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). The
      study aimed to quantify RBP4 serum standards in women with a wide range of body
      mass index (BMI) and glucose tolerance level. SUBJECTS AND METHODS: Cross
      sectional study was performed with 139 women divided into three groups: Group 1
      (lean-control, n = 45) and Group 2 (obese, n = 53) with normal glucose tolerance
      and group 3 (obese with T2DM, n = 41), called G1, G2 and G3. Were assessed
      clinical, biochemical, anthropometric and body composition parameters. RESULTS:
      According to data analysis, we obtained in G1 higher RBP4 levels (104.8 +/- 76.8
      ng/mL) when compared to G2 (87.9 +/- 38 ng/mL) and G3 (72.2 +/- 15.6 ng/mL)
      levels. Also, were found: in G1 positive correlations of RBP4 with BMI (r =
      0.253), glycated hemoglobin (r = 0.378) and fasting insulin (r = 0.336); in G2
      with glycated hemoglobin (r = 0.489); in G3 with glycated hemoglobin (r = 0.330),
      fasting glucose (r = 0.463), HOMA-IR (r = 0.481). CONCLUSIONS: Although RBP4 have
      shown lower levels in diabetic and obese, a strong correlation with HOMA-IR index
      highlights that, in our study, there is growing IR when there is an increasing in
      RBP4 levels.

PMID- 25372580
TI  - The prevalence of glucose metabolism disturbances in Chinese Muslims and possible
      risk factors: a study from northwest China.
AB  - OBJECTIVE: To survey the prevalence of diabetes mellitus (DM) and pre-diabetes
      mellitus (PDM) in the Muslim population in northwest China, and discuss the risk
      factor. MATERIALS AND METHODS: According to the income and the population, we
      randomly selected 3 villages with stratified and cluster sampling. The subjects
      were residents >= 20 years of age, and were from families which have been local
      for > 3 generations. The questionnaire and oral glucose tolerance test (OGTT)
      were completed and analyzed for 660 subjects. RESULTS: The prevalence of DM and
      PDM between the Han and Muslim populations were different (P = 0.041). And the
      prevalence were also different with respect to age in the Han (P < 0.001) and
      Muslim population (P < 0.001) respectively. Except for the 20-year-old age group
      the prevalence of DM and PDM within the Muslim population was higher than the Han
      (P = 0.013), we did not find any significant difference for other age groups (P >
      0.05). The intake of salt (P < 0.001) and edible oil (P < 0.001) in the Muslim
      population was higher than the Han, while cigarette smoking (P < 0.001) and
      alcohol consumption (P < 0.001) was lower. BMI (P < 0.001), age (P = 0.025), and
      smoking cigarettes (P = 0.011) were risk factors for DM and PDM, but alcohol
      consumption (P < 0.001) was a protective factor. CONCLUSIONS: In northwest China,
      the prevalence of DM was higher in the Muslim population, and it was special
      higher on the 20-year-old age compared to the Han. This might be explained by the
      potential genetic differences and poor dietary habits.

PMID- 25372581
TI  - [Evaluation of fructosamine as a parameter of blood glucose control in diabetic
      pregnant women].
AB  - OBJECTIVE: To evaluate the alternative parameters to monitor glycemia in pregnant
      women with diabetes studying the relationship between fructosamine testing and
      self monitoring of blood glucose in pregnant women with diabetes. MATERIALS AND
      METHODS: Serum fructosamine levels and the self monitoring of blood glucose over
      14 days before the collection of fructosamine were evaluated in 47 diabetic
      pregnant women. RESULTS: Seventy-one fructosamine levels and 2,238 glucose
      measurements (CGs) were analysed. Levels of fructosamine correlated with high
      blood glucose index (HBGI) and the standard deviation of glycemias (r = 0.28; p =
      0.021 and r = 0.26; p = 0.03, respectively). The comparison between the mothers
      of the newborns with appropriated or large birthweight and those who gave birth
      to small newborns for their gestational age (SGA) showed that the latter had a
      lower glycemic mean (105 vs. 114 and 119 mg/dL), a higher low blood glucose index
      (5.8 vs. 1.3 and 0.7) and a higher percentage of hyperglycemias (11 vs. 0 and 0%)
      even when the fructosamine falls within the reference values (242 vs. 218 and 213
      MUmol/l). CONCLUSION: The levels of fructosamine can be used as further parameter
      to aid self monitoring of blood glucose to evaluate hyperglycemias and glycemic
      variability, however, this can underestimate hypoglycemias in pregnant women
      carrying small-for-gestational age fetuses.

PMID- 25372582
TI  - Is it necessary to increase the dose of levothyroxine in patients with
      hypothyroidism who use omeprazole?
AB  - OBJECTIVE: It is believed that gastric pH interferes in levothyroxine absorption.
      Omeprazole, which acts by blocking the secretion of gastric acid, might interfere
      in hypothyroidism control in patients using levothyroxine and this effect could
      be dose dependent. The present study aimed to investigate this possibility.
      SUBJECTS AND METHODS: Twenty-one patients with primary hypothyroidism who had
      been using a stabilized levothyroxine dosage for at least one year were selected
      and randomly assigned to take omeprazole at the dosage of 40 mg or 20 mg per day.
      The mean levels of thyroid-stimulating hormone (TSH) before and 3 months after
      omeprazole usage were compared in the entire sample and in each group. RESULTS:
      Ten patients concluded the entire treatment protocol in the 20 mg group and nine
      patients in the 40 mg group. There was no significant difference in TSH levels
      before and 3 months after omeprazole treatment in the entire patient sample
      (median levels: 2.28 vs. 2.30 mU/L, respectively: p = 0.56). Analysis of each
      subgroup (20 and 40 mg) showed no significant variation in TSH levels before and
      3 months after omeprazole treatment (median levels: 2.24 vs. 2.42 mU/L, p = 0.62,
      and 2.28 vs. 2.30 mU/L, p = 0.82, respectively). No significant difference in the
      absolute (p = 0.93) or relative (p = 0.87) delta were observed between the two
      subgroups. CONCLUSION: Omeprazole in the dosage of 20 or 40 mg/day does not
      interfere in a clinically relevant manner in the treatment of patients with
      hypothyroidism that was previously under control.

PMID- 25372583
TI  - Zinc transporter 8 autoantibodies in patients with type 1 diabetes from a
      multiethnic population and their first degree relatives.
AB  - OBJECTIVE: Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in
      non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8
      autoantibodies in patients with T1D and their first degree relatives (FDR) from a
      multiethnic population, as well as its relation with the insulin (INS) or the
      protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms.
      SUBJECTS AND METHODS: ZnT8A were analyzed in sera from T1D patients (n = 72, mean
      age of 30.3 +/- 11.4 years) of variable duration (15.7 +/- 11.8 years) and their
      FDR (n = 78, mean age of 18.3 +/- 9.1 years) by a triple mix Radioligand Binding
      Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide
      polymorphism) for INS and PTPN22 were genotyped. RESULTS: The prevalence of ZnT8A
      was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001),
      ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with
      ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22
      was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p =
      0.038). CONCLUSIONS: ZnT8A is observed in non-Caucasian patients with T1D, even
      years after the disease onset, as well as in their FDR. In those, there was an
      overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22
      polymorphisms. Further longitudinal studies are necessary to elucidate the
      importance of these findings in the natural history of T1D patients with
      multiethnic background.

PMID- 25372584
TI  - The effect of weight reduction on antioxidant enzymes and their association with
      dietary intake of vitamins A, C and E.
AB  - OBJECTIVE: Our goal was to assess the effects of weight loss on antioxidant
      enzymes of red blood cells and it's relation with vitamins A, E and C intake in
      30 obese women. SUBJECTS AND METHODS: General information, anthropometric
      measurements, 3-day food recall, and fasting blood samples were collected from 30
      obese women at the beginning of the study and after 3 months intervention. Weight
      loss was set at about 10% of their weight before the intervention. RESULTS:
      Glutathione reductase and catalase activities showed a significant increase (P <
      0.01) after weight reduction, but no significant changes were seen in the
      superoxide dismutase and glutathione peroxidase activities. There was a positive
      linear correlation between daily vitamin C intake with superoxide dismutase
      enzyme after intervention (P = 0.004, r = 0.507). There was a negative linear
      correlation between vitamin E intake and glutathione peroxidase activity before
      intervention (P = 0.005, r = -0.5). A negative correlation was found between
      daily vitamin A intake and glutathione reductase enzyme before and after
      intervention (r = -0.385, r = -0.397, P < 0.05) respectively. No significant
      correlation was observed between vitamins A, C, E amounts and catalase activity.
      CONCLUSIONS: Ten percent weight reduction can have a significant role in
      increasing antioxidant enzymes activities, especially glutathione reductase, and
      catalase enzymes in obese women. However, it is important to take into
      consideration a balanced amount of certain nutrients while administering a diet
      with limited energy.

PMID- 25372585
TI  - [Impairment of muscle vasodilation during mental stress in women with subclinical
      hypothyroidism].
AB  - OBJECTIVE: To test the hypothesis that women with subclinical hypothyroidism (SH)
      have forearm vascular conductance (FVC) impaired during mental stress. SUBJECTS
      AND METHODS: We evaluated 20 women with SH and 21 euthyroid (Control group),
      matched for age (p = 0.699) and body mass index (p = 0.462). Muscle blood flow
      (MBF) was assessed by venous occlusion plethysmography and blood pressure by
      Dixtal2023. Both variables were recorded simultaneously for 3 minutes of baseline
      followed by 3 minutes of mental stress. The FVC was calculated by dividing MBF by
      mean arterial pressure. Significant differences were assumed at p < 0.05.
      RESULTS: The SH group had higher concentrations of thyroid stimulating hormone
      (7.57 +/- 3.17 vs. 2.10 +/- 0,88 mU/L, p < 0.001). At baseline, the SH and
      control groups were similar for MBF (2.50 +/- 0.79 vs. 2.55 +/- 0,71 mL/ min/100
      mL, p = 0.905, respectively) and FVC (2.80 +/- 0.90 vs. 2.92 +/- 0.88 units, p =
      0.952, respectively). Throughout the mental stress test the SH and Control groups
      increased the MBF (time effect, p < 0.001) and FVC (time effect, p < 0.001)
      compared to baseline protocol. However, these variables were lower in SH group
      during the first (MBF: 3.66 +/- 0.96 vs. 4.66 +/- 1,61 mL/min/100 mL, p = 0.018,
      FVC: 3.95 +/- 1.08 vs. 5.19 +/- 1,96 units, p = 0.010) and second (MBF: 3.55 +/-
      1.01 vs. 4.62 +/- 2,27 mL/min/100 ml, p = 0.018; FVC: 3.75 +/- 1.07 vs. 4.92 +/-
      2,37 units, p = 0.020) minutes of mental stress test. CONCLUSION: Women with SH
      have reduced muscle vasodilatatory response during mental stress.

PMID- 25372586
TI  - [Technical and functional aspects of catheterization of inferior petrosal sinuses
      in ACTH dependent Cushing's syndrome].
AB  - OBJECTIVE: To describe and analyze technique for bilateral catheterization of
      inferior petrosal sinus in our service, discussing the difficulties and success
      rates found. SUBJECTS AND METHODS: Fourteen patients with suspected Cushing's
      syndrome underwent bilateral inferior petrosal sinuses (IPS) catheterization
      between 2009 and 2012. The technique for catheterization and for hormone analysis
      were described. RESULTS: The procedure was well tolerated by all patients, and
      adequate catheterization was achieved in 92.85% of cases. The diagnosis of
      Cushing's disease was confirmed in 10 cases. The result of IPS catheterization
      after CRH infusion was coherent in all cases, without false negatives.
      CONCLUSION: The catheterization of IPS, despite being an invasive technique, is a
      safe procedure. The objectives can be done properly in most cases. When well
      indicated, this procedure remains the gold standard in distinguishing the ectopic
      form to pituitary source in Cushing's syndrome.

PMID- 25372587
TI  - Ten-year evaluation of a Neonatal Screening Program for congenital adrenal
      hyperplasia.
AB  - OBJECTIVE: Evaluate the Neonatal Screening Program (NSP) for congenital adrenal
      hyperplasia (CAH) of the Department of Health of the State of Santa Catarina
      (Secretaria de Estado da Saude de Santa Catarina, SES/SC), and provide
      information to improve the program. SUBJECTS AND METHODS: Descriptive,
      retrospective study of 748,395 children screened between January 2001 and
      December 2010. We analyzed the coverage of the NSP-SES/SC prevalence of CAH,
      child's age when the first sample for 17-hydroxyprogesterone (17OHP) measurement
      was collected, levels of 17OHP, mean age at treatment onset and main clinical
      manifestations. RESULTS: The NSP-SES/SC covered 89% of the live newborns in the
      State. It diagnosed 50 cases of CAH, yielding an incidence of 1:14,967. Mean age
      at collection of the first sample was 7.3 days and mean level of 17OHP was 152.9
      ng/mL. The most frequent manifestations were virilized genitalia with nonpalpable
      gonads, clitoromegaly and genital hyperpigmentation. In three girls, the genre
      established at birth was incorrect. The salt-wasting form was present in 74% of
      the cases. There was no occurrence of shock or death. Mean age at treatment onset
      in the salt-wasting form was 17.4 days compared with 54.9 days in those without
      the salt-wasting form of the disease. All children were treated with
      hydrocortisone, and those with salt-wasting CAH were also treated with
      fludrocortisone. CONCLUSIONS: The incidence of CAH was 1 case to 14,967 live
      newborns. Collection of the first sample occurred outside the recommended time,
      resulting in delays in treatment onset.

PMID- 25372588
TI  - Maturity onset diabetes of young type 2 due to a novel de novo GKC mutation.
AB  - Maturity Onset Diabetes of Young (MODY) is a heterogeneous group of monogenic
      disorders that result in beta-cell dysfunction, with an estimated prevalence of
      1%-2% in industrialized countries. MODY generally occurs in non-obese patients
      with negative autoantibodies presenting with mild to moderate hyperglycemia. The
      clinical features of the patients are heterogeneous, depending on the different
      genetic subtypes. We pretend to report a case of MODY type 2 caused by a novel de
      novo CGK mutation, highlighting the importance of the differential diagnosis in
      pediatric diabetes. A 13-year-old, healthy and non-obese girl was admitted for
      investigation of recurrent hyperglycemia episodes. She presented with persistent
      high levels of fasting blood glycemia (> 11.1 mmol/L) and had no familial history
      of diabetes. The blood glucose profile revealed an impaired fasting glucose of
      124 mg/dL (6,9 mmol/L) with a normal oral glucose tolerance test. Fasting
      insulinemia was 15 mg/dL (90.1 pmol/L), HOMA-IR was 3.9 and hemoglobin A1c was
      7.1%. Pancreatic autoantibodies were negative. Genetic testing identified a novel
      missense heterozygous mutation in exon 5 of GCK gene c.509G > T (p.Gly170Val),
      not present on the parents. This result established the diagnosis of MODY type 2.
      Clinical identification of patients with MODY remains a diagnostic challenge,
      especially when familial history is absent. Molecular diagnosis is very important
      for establishing an individualized treatment and providing a long term prognosis
      for each type of MODY.

PMID- 25372589
TI  - A rare case of a parathyroid adenoma inside a parathyroid cyst.
AB  - Parathyroid cysts (PCs) are rare lesions, located in the neck and anterior
      mediastinal region. The vast majority are non-functioning, presented as nodular
      cervical lesions. Large, non-functioning PCs can manifest with compressive
      symptoms of the surrounding tissues. Rarely, PCs produce excessive amounts of
      parathyroid hormone (PTH), resulting in primary hyperparathyroidism. We report a
      case of functional PC, describing its diagnostic and therapeutic approach.

PMID- 25372590
TI  - [Thyrotoxic hypokalemic periodic paralysis in patients of African descent].
AB  - Thyrotoxic hypokalemic periodic paralysis (THPP) is an endocrine emergency marked
      by recurrent attacks of muscle weakness associated with hypokalemia and
      thyrotoxicosis. Asiatic male patients are most often affected. On the other hand,
      African descents rarely present this disease. The case described shows an
      afrodescendant patient with hypokalemia and tetraparesis, whose diagnosis of
      hyperthyroidism was considered during this crisis. The THPP, although rare, is
      potentially lethal. Therefore, in cases of flaccid paresis crisis this diagnosis
      should always be considered, especially if associated with hypokalemia. In this
      situation, if no previous diagnosis of hyperthyroidism, this should also be
      regarded.

PMID- 25372591
TI  - Systematic methodology for the development of biocatalytic hydrogen-borrowing
      cascades: application to the synthesis of chiral alpha-substituted carboxylic
      acids from alpha-substituted alpha,beta-unsaturated aldehydes.
AB  - Ene-reductases (ERs) are flavin dependent enzymes that catalyze the asymmetric
      reduction of activated carbon-carbon double bonds. In particular, alpha,beta
      unsaturated carbonyl compounds (e.g. enals and enones) as well as nitroalkenes
      are rapidly reduced. Conversely, alpha,beta-unsaturated esters are poorly
      accepted substrates whereas free carboxylic acids are not converted at all. The
      only exceptions are alpha,beta-unsaturated diacids, diesters as well as esters
      bearing an electron-withdrawing group in alpha- or beta-position. Here, we
      present an alternative approach that has a general applicability for directly
      obtaining diverse chiral alpha-substituted carboxylic acids. This approach
      combines two enzyme classes, namely ERs and aldehyde dehydrogenases (Ald-DHs), in
      a concurrent reductive-oxidative biocatalytic cascade. This strategy has several
      advantages as the starting material is an alpha-substituted alpha,beta
      unsaturated aldehyde, a class of compounds extremely reactive for the reduction
      of the alkene moiety. Furthermore no external hydride source from a sacrificial
      substrate (e.g. glucose, formate) is required since the hydride for the first
      reductive step is liberated in the second oxidative step. Such a process is
      defined as a hydrogen-borrowing cascade. This methodology has wide applicability
      as it was successfully applied to the synthesis of chiral substituted
      hydrocinnamic acids, aliphatic acids, heterocycles and even acetylated amino
      acids with elevated yield, chemo- and stereo-selectivity. A systematic
      methodology for optimizing the hydrogen-borrowing two-enzyme synthesis of alpha
      chiral substituted carboxylic acids was developed. This systematic methodology
      has general applicability for the development of diverse hydrogen-borrowing
      processes that possess the highest atom efficiency and the lowest environmental
      impact. 

PMID- 25372594
TI  - Changes in refractive errors related to spectacle correction of hyperopia.
AB  - BACKGROUND: Hyperopic undercorrection is a common clinical practice. However,
      less is known of its effect on the change in refractive errors and
      emmetropization throughout the later years of childhood. OBJECTIVES: To evaluate
      the effect of spectacle correction on the change in refractive errors in
      hyperopic children less than 12 years of age with or without strabismus. DATA
      EXTRACTION: A retrospective cohort study was performed by a computer based search
      of the hospital database of patients with hyperopia, accommodative esotropia or
      exotropia. A total of 150 hyperopic children under 12 years of age were included.
      Patients were classified into four groups: 1) accommodative esotropia with full
      correction of hyperopia, 2) exotropia with undercorrection of hyperopia, 3)
      orthotropia with full correction of hyperopia, 4) orthotropia with
      undercorrection of hyperopia. The 4 groups were matched by initial age on
      examination and spherical equivalent refractive errors (SER). The main outcome
      measure was the change in SER (Diopter/year) in both eyes after two years of
      follow-up. RESULTS: An overall negative shift in SER was noted during the follow
      up period in all groups, except for the group with esotropia and full correction.
      The mean negative shift of hyperopia was more rapid in groups receiving
      undercorrection of hyperopia with or without strabismus. The amount of
      undercorrection of hyperopia was positively correlated to the magnitude of
      decrease in hyperopia in all patients (r = 0.289, P<0.001) and in the subgroup of
      patients with orthotropia (r = 0.304, P = 0.011). The amount of undercorrection
      of hyperopia was the only factor associated with a more negative shift in SER
      (OR, 2.414; 95% CI, 1.202-4.849; P = 0.013). CONCLUSIONS: The amount of
      undercorrection is significantly correlated to the change in hyperopic refractive
      errors. Full correction of hyperopia may inhibit emmetropization during early and
      late childhood.

PMID- 25372592
TI  - Exonic variants associated with development of aspirin exacerbated respiratory
      diseases.
AB  - Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often
      occurring in the form of a severe and sudden attack. Due to the time-consuming
      nature and difficulty of oral aspirin challenge (OAC) for AERD diagnosis, non
      invasive biomarkers have been sought. The aim of this study was to identify AERD
      associated exonic SNPs and examine the diagnostic potential of a combination of
      these candidate SNPs to predict AERD. DNA from 165 AERD patients, 397 subjects
      with aspirin-tolerant asthma (ATA), and 398 normal controls were subjected to an
      Exome BeadChip assay containing 240K SNPs. 1,023 models (210-1) were generated
      from combinations of the top 10 SNPs, selected by the p-values in association
      with AERD. The area under the curve (AUC) of the receiver operating
      characteristic (ROC) curves was calculated for each model. SNP Function Portal
      and PolyPhen-2 were used to validate the functional significance of candidate
      SNPs. An exonic SNP, exm537513 in HLA-DPB1, showed the lowest p-value (p =
      3.40*10-8) in its association with AERD risk. From the top 10 SNPs, a combination
      model of 7 SNPs (exm537513, exm83523, exm1884673, exm538564, exm2264237,
      exm396794, and exm791954) showed the best AUC of 0.75 (asymptotic p-value of
      7.94*10-21), with 34% sensitivity and 93% specificity to discriminate AERD from
      ATA. Amino acid changes due to exm83523 in CHIA were predicted to be "probably
      damaging" to the structure and function of the protein, with a high score of '1'.
      A combination model of seven SNPs may provide a useful, non-invasive genetic
      marker combination for predicting AERD. 

PMID- 25372595
TI  - Clinical significance of intensive endoscopic screening for synchronous
      esophageal neoplasm in patients with head and neck squamous cell carcinoma.
AB  - OBJECTIVES: Patients with head and neck squamous cell carcinoma (HNSCC) often
      develop second primary tumors in the upper aerodigestive tract. Early detection
      of synchronous esophageal squamous cell neoplasm (ESCN) is important because the
      prognosis of HNSCC can be affected by the statuses of second primary tumors.
      METHODS: In a prospective study, 308 patients with HNSCC were screened for
      synchronous ESCN between May 2010 and April 2012. All patients underwent
      conventional white-light endoscopic examination with Lugol chromoendoscopy and
      narrow band image. RESULTS: The median age was 61 years (range, 26-87 years), and
      the male-to-female ratio was 4.2:1. Two hundred and thirty-four patients (76.0%)
      were current or ex-smokers, 207 patients (67.2%) had a history of alcohol
      consumption and 56 patients (18.2%) had previous history of cancer. Synchronous
      ESCN was detected in 22 patients (7.1%), and most patients were at an early
      stage. The locations of index HNSCC in these patients were as follows:
      hypopharynx (n = 12), larynx (n = 6), oropharynx (n = 2) and oral cavity (n = 2).
      Synchronous ESCN was detected in 25.5% (12/47) of hypopharyngeal cancer and in
      27.8% (15/54) of HNSCC involving the pyriform sinus. Multivariate analysis showed
      that smoking (current smoker vs. never smoker, Odds Ratio [OR] 8.3, p = 0.028), a
      history of cancer (OR 5.0, p = 0.002) and pyriform sinus involvement (OR 9.2, p <
      0.0001) increased the risk of developing synchronous ESCN. CONCLUSIONS: Patients
      with HNSCC, especially those who are current smokers, have a history of cancer
      and have pyriform sinus involvement, should undergo intensive endoscopic
      screening to detect synchronous ESCN.

PMID- 25372597
TI  - Lights, camera...citizen science: assessing the effectiveness of smartphone-based
      video training in invasive plant identification.
AB  - The rapid growth and increasing popularity of smartphone technology is putting
      sophisticated data-collection tools in the hands of more and more citizens. This
      has exciting implications for the expanding field of citizen science. With
      smartphone-based applications (apps), it is now increasingly practical to
      remotely acquire high quality citizen-submitted data at a fraction of the cost of
      a traditional study. Yet, one impediment to citizen science projects is the
      question of how to train participants. The traditional "in-person" training
      model, while effective, can be cost prohibitive as the spatial scale of a project
      increases. To explore possible solutions, we analyze three training models: 1) in
      person, 2) app-based video, and 3) app-based text/images in the context of
      invasive plant identification in Massachusetts. Encouragingly, we find that
      participants who received video training were as successful at invasive plant
      identification as those trained in-person, while those receiving just text/images
      were less successful. This finding has implications for a variety of citizen
      science projects that need alternative methods to effectively train participants
      when in-person training is impractical. 

PMID- 25372596
TI  - Households across all income quintiles, especially the poorest, increased animal
      source food expenditures substantially during recent Peruvian economic growth.
AB  - BACKGROUND: Relative to plant-based foods, animal source foods (ASFs) are richer
      in accessible protein, iron, zinc, calcium, vitamin B-12 and other nutrients.
      Because of their nutritional value, particularly for childhood growth and
      nutrition, it is important to identify factors influencing ASF consumption,
      especially for poorer households that generally consume less ASFs. OBJECTIVE: To
      estimate differential responsiveness of ASF consumption to changes in total
      household expenditures for households with different expenditures in a middle
      income country with substantial recent income increases. METHODS: The Peruvian
      Young Lives household panel (n = 1750) from 2002, 2006 and 2009 was used to
      characterize patterns of ASF expenditures. Multivariate models with controls for
      unobserved household fixed effects and common secular trends were used to examine
      nonlinear relationships between changes in household expenditures and in ASF
      expenditures. RESULTS: Households with lower total expenditures dedicated greater
      percentages of expenditures to food (58.4% vs.17.9% in 2002 and 24.2% vs. 21.5%
      in 2009 for lowest and highest quintiles respectively) and lower percentages of
      food expenditures to ASF (22.8% vs. 33.9% in 2002 and 30.3% vs. 37.6% in 2009 for
      lowest and highest quintiles respectively). Average percentages of overall
      expenditures spent on food dropped from 47% to 23.2% between 2002 and 2009.
      Households in the lowest quintiles of expenditures showed greater increases in
      ASF expenditures relative to total consumption than households in the highest
      quintiles. Among ASF components, meat and poultry expenditures increased more
      than proportionately for households in the lowest quintiles, and eggs and fish
      expenditures increased less than proportionately for all households. CONCLUSIONS:
      Increases in household expenditures were associated with substantial increases in
      consumption of ASFs for households, particularly households with lower total
      expenditures. Increases in ASF expenditures for all but the top quintile of
      households were proportionately greater than increases in total food
      expenditures, and proportionately less than overall expenditures.

PMID- 25372598
TI  - Impact of the Changes in the End Stage Renal Disease Composite Rate.
AB  - The following summary is of a report from the Secretary of Health and Human
      Services released to Congress on December 30, 1988.

PMID- 25372599
TI  - Respondent.

PMID- 25372600
TI  - The transient receptor potential cation channel subfamily V member 6 (TRPV6):
      genetics, biochemical properties, and functions of exceptional calcium channel
      proteins.
AB  - The transient receptor potential cation channel subfamily V member 6 (TRPV6) gene
      and cDNA were identified 15 years ago and exceptional observations on TrpV6
      proteins and their function as a Ca(2+)-selective cation channel have been made
      since then. In this review we will summarize recent studies regarding the
      genetics, biochemical properties, and physiological functions of murine and human
      TrpV6 channel proteins. We will focus on TRPV6 gene polymorphisms, the start of
      TRPV6 translation at a non-AUG codon and the functions of TRPV6 in intestinal
      Ca(2+) uptake, sperm maturation, and male fertility. 

PMID- 25372601
TI  - Tetrahydroxanthene-1,3(2H)-dione derivatives from Uvaria valderramensis.
AB  - Two tetrahydroxanthene-1,3(2H)-dione metabolites, valderramenols A (1) and B (2),
      were isolated from the Philippine endemic Annonaceous species Uvaria
      valderramensis. Planar structures of the rac-xanthene-1,3-(2H)-diones 1 and 2
      were established by MS and NMR measurements. Their enantiomers were separated by
      chiral HPLC, and the absolute configurations of the separated enantiomers were
      determined by comparison of the HPLC-ECD spectra with computed TDDFT-generated
      spectra. A TDDFT-ECD study of the known grandiuvarone (3) allowed the revision of
      its absolute configuration as S. Compound 1 showed antitubercular activity (MIC
      10 MUg/mL), while 3 and 4 had weaker activities (MIC 32 MUg/mL). Oxepinone 3
      exhibited cytotoxic activity against KB-562, a chronic myeloid leukemia cell
      line. 

PMID- 25372602
TI  - Does Health Status Explain Higher Medicare Costs of Medicaid Enrollees?
AB  - In this article, the authors present findings on differences in Medicare costs
      between elderly beneficiaries who are dually eligible for Medicare and Medicaid
      and other Medicare beneficiaries. Data from the Medicare Current Beneficiary
      Survey (MCBS) were used in the analysis. After controlling for health and
      functional-status differences, the higher Medicare costs of dually eligible
      persons, relative to other enrollees, was reduced from 282 percent to 45 percent.

PMID- 25372603
TI  - A novel gain-of-function mutation of the proneural IRX1 and IRX2 genes disrupts
      axis elongation in the Araucana rumpless chicken.
AB  - Axis elongation of the vertebrate embryo involves the generation of cell lineages
      from posterior progenitor populations. We investigated the molecular mechanism
      governing axis elongation in vertebrates using the Araucana rumpless chicken.
      Araucana embryos exhibit a defect in axis elongation, failing to form the
      terminal somites and concomitant free caudal vertebrae, pygostyle, and associated
      tissues of the tail. Through whole genome sequencing of six Araucana we have
      identified a critical 130 kb region, containing two candidate causative SNPs.
      Both SNPs are proximal to the IRX1 and IRX2 genes, which are required for neural
      specification. We show that IRX1 and IRX2 are both misexpressed within the
      bipotential chordoneural hinge progenitor population of Araucana embryos.
      Expression analysis of BRA and TBX6, required for specification of mesoderm,
      shows that both are downregulated, whereas SOX2, required for neural patterning,
      is expressed in ectopic epithelial tissue. Finally, we show downregulation of
      genes required for the protection and maintenance of the tailbud progenitor
      population from the effects of retinoic acid. Our results support a model where
      the disruption in balance of mesoderm and neural fate results in early depletion
      of the progenitor population as excess neural tissue forms at the expense of
      mesoderm, leading to too few mesoderm cells to form the terminal somites.
      Together this cascade of events leads to axis truncation. 

PMID- 25372604
TI  - Folded monomers and hexamers of the ectodomain of the HIV gp41 membrane fusion
      protein: potential roles in fusion and synergy between the fusion peptide,
      hairpin, and membrane-proximal external region.
AB  - HIV is an enveloped virus and fusion between the HIV and host cell membranes is
      catalyzed by the ectodomain of the HIV gp41 membrane protein. Both the N-terminal
      fusion peptide (FP) and C-terminal membrane-proximal external region (MPER) are
      critical for fusion and are postulated to bind to the host cell and HIV
      membranes, respectively. Prior to fusion, the gp41 on the virion is a trimer in
      noncovalent complex with larger gp120 subunits. The gp120 bind host cell
      receptors and move away or dissociate from gp41 which subsequently catalyzes
      fusion. In the present work, large gp41 ectodomain constructs were produced and
      biophysically and structurally characterized. One significant finding is
      observation of synergy between the FP, hairpin, and MPER in vesicle fusion. The
      ectodomain-induced fusion can be very efficient with only ~15 gp41 per vesicle,
      which is comparable to the number of gp41 on a virion. Conditions are found with
      predominant monomer or hexamer but not trimer and these may be oligomeric states
      during fusion. Monomer gp41 ectodomain is hyperthermostable and has helical
      hairpin structure. A new HIV fusion model is presented where (1) hemifusion is
      catalyzed by folding of gp41 ectodomain monomers into hairpins and (2) subsequent
      fusion steps are catalyzed by assembly into a hexamer with FPs in an antiparallel
      beta sheet. There is also significant interest in the gp41 MPER because it is the
      epitope of several broadly neutralizing antibodies. Two of these antibodies bind
      our gp41 ectodomain constructs and support investigation of the gp41 ectodomain
      as an immunogen in HIV vaccine development. 

PMID- 25372605
TI  - A novel cytosolic NADH:quinone oxidoreductase from Methanothermobacter
      marburgensis.
AB  - Methanothermobacter marburgensis is a strictly anaerobic, thermophilic
      methanogenic archaeon that uses methanogenesis to convert H2 and CO2 to energy.
      M. marburgensis is one of the best-studied methanogens, and all genes required
      for methanogenic metabolism have been identified. Nonetheless, the present study
      describes a gene (Gene ID 9704440) coding for a putative NAD(P)H: quinone
      oxidoreductase that has not yet been identified as part of the metabolic
      machinery. The gene product, MmNQO, was successfully expressed, purified and
      characterized biochemically, as well as structurally. MmNQO was identified as a
      flavin-dependent NADH:quinone oxidoreductase with the capacity to oxidize NADH in
      the presence of a wide range of electron acceptors, whereas NADPH was oxidized
      with only three acceptors. The 1.50 A crystal structure of MmNQO features a
      homodimeric enzyme where each monomer comprises 196 residues folding into
      flavodoxin-like alpha/beta domains with non-covalently bound FMN (flavin
      mononucleotide). The closest structural homologue is the modulator of drug
      activity B from Streptococcus mutans with 1.6 A root-mean-square deviation on 161
      Calpha atoms and 28% amino-acid sequence identity. The low similarity at sequence
      and structural level suggests that MmNQO is unique among NADH:quinone
      oxidoreductases characterized to date. Based on preliminary bioreactor
      experiments, MmNQO could provide a useful tool to prevent overflow metabolism in
      applications that require cells with high energy demand.

PMID- 25372606
TI  - Global systematic review of the cost-effectiveness of indigenous health
      interventions.
AB  - BACKGROUND: Indigenous populations around the world have consistently been shown
      to bear a greater burden of disease, death and disability than their non
      Indigenous counterparts. Despite this, little is known about what constitutes
      cost-effective interventions in these groups. The objective of this paper was to
      assess the global cost-effectiveness literature in Indigenous health to identify
      characteristics of successful and unsuccessful interventions and highlight areas
      for further research. METHODS AND FINDINGS: A systematic review of the published
      literature was carried out. MEDLINE, PSYCINFO, ECONLIT, EMBASE and CINAHL were
      searched with terms to identify cost-effectiveness evaluations of interventions
      in Indigenous populations around the world. The WHO definition was followed in
      identifying Indigenous populations. 19 studies reporting on 27 interventions were
      included in the review. The majority of studies came from high-income nations
      with only two studies of interventions in low and middle-income nations. 22 of
      the 27 interventions included in the analysis were found to be cost-effective or
      cost-saving by the respective studies. There were only two studies that focused
      on Indigenous communities in urban areas, neither of which was found to be cost
      effective. There was little attention paid to Indigenous conceptions of health in
      included studies. Of the 27 included studies, 23 were interventions that
      specifically targeted Indigenous populations. Outreach programs were shown to be
      consistently cost-effective. CONCLUSION: The comprehensive review found only a
      small number of studies examining the cost-effectiveness of interventions into
      Indigenous communities around the world. Given the persistent disparities in
      health outcomes faced by these populations and commitments from governments
      around the world to improving these outcomes, it is an area where the health
      economics and public health fields can play an important role in improving the
      health of millions of people.

PMID- 25372607
TI  - Multilayered polyelectrolyte microcapsules: interaction with the enzyme
      cytochrome C oxidase.
AB  - Cell-sized polyelectrolyte capsules functionalized with a redox-driven proton
      pump protein were assembled for the first time. The interaction of
      polyelectrolyte microcapsules, fabricated by electrostatic layer-by-layer
      assembly, with cytochrome c oxidase molecules was investigated. We found that the
      cytochrome c oxidase retained its functionality, that the functionalized
      microcapsules interacting with cytochrome c oxidase were permeable and that the
      permeability characteristics of the microcapsule shell depend on the shell
      components. This work provides a significant input towards the fabrication of an
      integrated device made of biological components and based on specific
      biomolecular functions and properties. 

PMID- 25372608
TI  - Isolation of specific neurons from C. elegans larvae for gene expression
      profiling.
AB  - BACKGROUND: The simple and well-described structure of the C. elegans nervous
      system offers an unprecedented opportunity to identify the genetic programs that
      define the connectivity and function of individual neurons and their circuits. A
      correspondingly precise gene expression map of C. elegans neurons would
      facilitate the application of genetic methods toward this goal. Here we describe
      a powerful new approach, SeqCeL (RNA-Seq of C. elegans cells) for producing gene
      expression profiles of specific larval C. elegans neurons. METHODS AND RESULTS:
      We have exploited available GFP reporter lines for FACS isolation of specific
      larval C. elegans neurons for RNA-Seq analysis. Our analysis showed that diverse
      classes of neurons are accessible to this approach. To demonstrate the
      applicability of this strategy to rare neuron types, we generated RNA-Seq
      profiles of the NSM serotonergic neurons that occur as a single bilateral pair of
      cells in the C. elegans pharynx. These data detected >1,000 NSM enriched
      transcripts, including the majority of previously known NSM-expressed genes.
      SIGNIFICANCE: This work offers a simple and robust protocol for expression
      profiling studies of post-embryonic C. elegans neurons and thus provides an
      important new method for identifying candidate genes for key roles in neuron
      specific development and function.

PMID- 25372609
TI  - Sleep is associated with offline improvement of motor sequence skill in children.
AB  - In adults, sleep is necessary for the offline improvement of certain skills, such
      as sequential finger tapping, but whether children show a similar effect is still
      debatable. Here, we tested whether sleep is associated with offline performance
      improvement in children. Nine- and 11-year-old children trained on an explicit
      sequential finger tapping task. On the night following training, their parents
      observed and recorded the duration of each child's sleep. The following day, all
      children performed a surprise retest session on the previously trained sequence.
      In both 9- and 11-year-old children, skill performance was significantly improved
      during the first retest session relative to the end of training on the previous
      day, confirming the offline improvement in performance. There was a significant
      correlation between the degree of improvement and sleep duration the night after
      training, suggesting that in children, as in adults, sleep is associated with
      offline skill enhancement. 

PMID- 25372611
TI  - Editorial Policy.

PMID- 25372612
TI  - Profile of Medicare Beneficiaries With AIDS: Application of an AIDS Casefinding
      Algorithm.
AB  - This profile of Medicare beneficiaries with acquired immunodeficiency syndrome
      (AIDS) was developed by applying a casefinding algorithm to virtually all
      Medicare claims from 1991-93. The algorithm identified more than 37,000
      beneficiaries with AIDS, approximately 21,000 of whom were living at the end of
      1993. These estimates suggest that as many as 12 percent of people living with
      AIDS at the end of 1993 were covered by Medicare. Medicare expenditures for these
      beneficiaries averaged more than $2,400 per month and totaled more than $500
      million in 1993. These expenditures are likely to rise as more people with AIDS
      live long enough to qualify for Medicare coverage.

PMID- 25372610
TI  - Positive selection of deleterious alleles through interaction with a sex-ratio
      suppressor gene in African Buffalo: a plausible new mechanism for a high
      frequency anomaly.
AB  - Although generally rare, deleterious alleles can become common through genetic
      drift, hitchhiking or reductions in selective constraints. Here we present a
      possible new mechanism that explains the attainment of high frequencies of
      deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger
      National Park, through positive selection of these alleles that is ultimately
      driven by a sex-ratio suppressor. We have previously shown that one in four
      Kruger buffalo has a Y-chromosome profile that, despite being associated with low
      body condition, appears to impart a relative reproductive advantage, and which is
      stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio
      suppressor prevents fertility reduction that generally accompanies sex-ratio
      distortion. We hypothesize that this body-condition-associated reproductive
      advantage increases the fitness of alleles that negatively affect male body
      condition, causing genome-wide positive selection of these alleles. To
      investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By
      correlating heterozygosity with body condition (heterozygosity-fitness
      correlations), we found that most microsatellites were associated with one of two
      gene types: one with elevated frequencies of deleterious alleles that have a
      negative effect on body condition, irrespective of sex; the other with elevated
      frequencies of sexually antagonistic alleles that are negative for male body
      condition but positive for female body condition. Positive selection and a direct
      association with a Y-chromosomal sex-ratio suppressor are indicated,
      respectively, by allele clines and by relatively high numbers of homozygous
      deleterious alleles among sex-ratio suppressor carriers. This study, which
      employs novel statistical techniques to analyse heterozygosity-fitness
      correlations, is the first to demonstrate the abundance of sexually-antagonistic
      genes in a natural mammal population. It also has important implications for our
      understanding not only of the evolutionary and ecological dynamics of sex-ratio
      distorters and suppressors, but also of the functioning of deleterious and
      sexually-antagonistic alleles, and their impact on population viability. 

PMID- 25372614
TI  - Projected carbon dioxide to increase grass pollen and allergen exposure despite
      higher ozone levels.
AB  - One expected effect of climate change on human health is increasing allergic and
      asthmatic symptoms through changes in pollen biology. Allergic diseases have a
      large impact on human health globally, with 10-30% of the population affected by
      allergic rhinitis and more than 300 million affected by asthma. Pollen from grass
      species, which are highly allergenic and occur worldwide, elicits allergic
      responses in 20% of the general population and 40% of atopic individuals. Here we
      examine the effects of elevated levels of two greenhouse gases, carbon dioxide
      (CO2), a growth and reproductive stimulator of plants, and ozone (O3), a
      repressor, on pollen and allergen production in Timothy grass (Phleum pratense
      L.). We conducted a fully factorial experiment in which plants were grown at
      ambient and/or elevated levels of O3 and CO2, to simulate present and projected
      levels of both gases and their potential interactive effects. We captured and
      counted pollen from flowers in each treatment and assayed for concentrations of
      the allergen protein, Phl p 5. We found that elevated levels of CO2 increased the
      amount of grass pollen produced by ~50% per flower, regardless of O3 levels.
      Elevated O3 significantly reduced the Phl p 5 content of the pollen but the net
      effect of rising pollen numbers with elevated CO2 indicate increased allergen
      exposure under elevated levels of both greenhouse gases. Using quantitative
      estimates of increased pollen production and number of flowering plants per
      treatment, we estimated that airborne grass pollen concentrations will increase
      in the future up to ~200%. Due to the widespread existence of grasses and the
      particular importance of P. pratense in eliciting allergic responses, our
      findings provide evidence for significant impacts on human health worldwide as a
      result of future climate change. 

PMID- 25372613
TI  - Chronic exposure to combined carcinogens enhances breast cell carcinogenesis with
      mesenchymal and stem-like cell properties.
AB  - Breast cancer is the most common type of cancer affecting women in North America
      and Europe. More than 85% of breast cancers are sporadic and attributable to long
      term exposure to small quantities of multiple carcinogens. To understand how
      multiple carcinogens act together to induce cellular carcinogenesis, we studied
      the activity of environmental carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) and benzo[a]pyrene (B[a]P), and dietary carcinogen 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using our breast cell carcinogenesis
      model. Our study revealed, for the first time, that combined NNK and B[a]P
      enhanced breast cell carcinogenesis chronically induced by PhIP in both non
      cancerous and cancerous breast cells. Co-exposure was more potent than sequential
      exposure to combined NNK and B[a]P followed by PhIP in inducing carcinogenesis.
      Initiation of carcinogenesis was measured by transient endpoints induced in a
      single exposure, while progression of carcinogenesis was measured by acquisition
      of constitutive endpoints in cumulative exposures. Transient endpoints included
      DNA damage, Ras-Erk-Nox pathway activation, reactive oxygen species elevation,
      and increased cellular proliferation. Constitutive endpoints included various
      cancer-associated properties and signaling modulators, as well as enrichment of
      cancer stem-like cell population and activation of the epithelial-to-mesenchymal
      transition program. Using transient and constitutive endpoints as targets, we
      detected that a combination of the green tea catechins ECG and EGCG, at non
      cytotoxic levels, was more effective than individual agents in intervention of
      cellular carcinogenesis induced by combined NNK, B[a]P, and PhIP. Thus, use of
      combined ECG and EGCG should be seriously considered for early intervention of
      breast cell carcinogenesis associated with long-term exposure to environmental
      and dietary carcinogens. 

PMID- 25372615
TI  - Direct observation of key photoinduced dynamics in a potential nano-delivery
      vehicle of cancer drugs.
AB  - In recent times, significant achievements in the use of zinc oxide (ZnO)
      nanoparticles (NPs) as delivery vehicles of cancer drugs have been made. The
      present study is an attempt to explore the key photoinduced dynamics in ZnO NPs
      upon complexation with a model cancer drug protoporphyrin IX (PP). The nanohybrid
      has been characterized by FTIR, Raman scattering and UV-Vis absorption
      spectroscopy. Picosecond-resolved Forster resonance energy transfer (FRET) from
      the defect mediated emission of ZnO NPs to PP has been used to study the
      formation of the nanohybrid at the molecular level. Picosecond-resolved
      fluorescence studies of PP-ZnO nanohybrids reveal efficient electron migration
      from photoexcited PP to ZnO, eventually enhancing the ROS activity. The
      dichlorofluorescin (DCFH) oxidation and no oxidation of luminol in PP/PP-ZnO
      nanohybrids upon green light illumination unravel that the nature of ROS is
      essentially singlet oxygen rather than superoxide anions. Surface mediated
      photocatalysis of methylene blue (MB) in an aqueous solution of the nanohybrid
      has also been investigated. Direct evidence of the role of electron transfer as a
      key player in enhanced ROS generation from the nanohybrid is also clear from the
      photocurrent measurement studies. We have also used the nanohybrid in a model
      photodynamic therapy application in a light sensitized bacteriological culture
      experiment. 

PMID- 25372617
TI  - A novel wireless and temperature-compensated SAW vibration sensor.
AB  - A novel wireless and passive surface acoustic wave (SAW) based temperature
      compensated vibration sensor utilizing a flexible Y-cut quartz cantilever beam
      with a relatively substantial proof mass and two one-port resonators is
      developed. One resonator acts as the sensing device adjacent to the clamped end
      for maximum strain sensitivity, and the other one is used as the reference
      located on clamped end for temperature compensation for vibration sensor through
      the differential approach. Vibration directed to the proof mass flex the
      cantilever, inducing relative changes in the acoustic propagation characteristics
      of the SAW travelling along the sensing device, and generated output signal
      varies in frequency as a function of vibration.  A theoretical mode using the
      Rayleigh method was established to determine the optimal dimensions of the
      cantilever beam. Coupling of Modes (COM) model was used to extract the optimal
      design parameters of the SAW devices prior to fabrication. The performance of the
      developed SAW sensor attached to an antenna towards applied vibration was
      evaluated wirelessly by using the precise vibration table, programmable incubator
      chamber, and reader unit.  High vibration sensitivity of ~10.4 kHz/g, good
      temperature stability, and excellent linearity were observed in the wireless
      measurements. 

PMID- 25372616
TI  - Simulation of the recharging method of implantable biosensors based on a wearable
      incoherent light source.
AB  - Recharging implantable electronics from the outside of the human body is very
      important for applications such as implantable biosensors and other implantable
      electronics. In this paper, a recharging method for implantable biosensors based
      on a wearable incoherent light source has been proposed and simulated. Firstly,
      we develop a model of the incoherent light source and a multi-layer model of skin
      tissue. Secondly, the recharging processes of the proposed method have been
      simulated and tested experimentally, whereby some important conclusions have been
      reached. Our results indicate that the proposed method will offer a convenient,
      safe and low-cost recharging method for implantable biosensors, which should
      promote the application of implantable electronics. 

PMID- 25372618
TI  - An SVM-based classifier for estimating the state of various rotating components
      in agro-industrial machinery with a vibration signal acquired from a single point
      on the machine chassis.
AB  - The goal of this article is to assess the feasibility of estimating the state of
      various rotating components in agro-industrial machinery by employing just one
      vibration signal acquired from a single point on the machine chassis. To do so, a
      Support Vector Machine (SVM)-based system is employed. Experimental tests
      evaluated this system by acquiring vibration data from a single point of an
      agricultural harvester, while varying several of its working conditions. The
      whole process included two major steps. Initially, the vibration data were
      preprocessed through twelve feature extraction algorithms, after which the
      Exhaustive Search method selected the most suitable features. Secondly, the SVM
      based system accuracy was evaluated by using Leave-One-Out cross-validation, with
      the selected features as the input data. The results of this study provide
      evidence that (i) accurate estimation of the status of various rotating
      components in agro-industrial machinery is possible by processing the vibration
      signal acquired from a single point on the machine structure; (ii) the vibration
      signal can be acquired with a uniaxial accelerometer, the orientation of which
      does not significantly affect the classification accuracy; and, (iii) when using
      an SVM classifier, an 85% mean cross-validation accuracy can be reached, which
      only requires a maximum of seven features as its input, and no significant
      improvements are noted between the use of either nonlinear or linear kernels. 

PMID- 25372619
TI  - A target model construction algorithm for robust real-time mean-shift tracking.
AB  - Mean-shift tracking has gained more interests, nowadays, aided by its feasibility
      of real-time and reliable tracker implementation. In order to reduce background
      clutter interference to mean-shift object tracking, this paper proposes a novel
      indicator function generation method. The proposed method takes advantage of two
      'a priori' knowledge elements, which are inherent to a kernel support for
      initializing a target model. Based on the assured background labels, a gradient
      based label propagation is performed, resulting in a number of objects
      differentiated from the background. Then the proposed region growing scheme picks
      up one largest target object near the center of the kernel support. The grown
      object region constitutes the proposed indicator function and this allows an
      exact target model construction for robust mean-shift tracking. Simulation
      results demonstrate the proposed exact target model could significantly enhance
      the robustness as well as the accuracy of mean-shift object tracking. 

PMID- 25372620
TI  - Adaptive activity and environment recognition for mobile phones.
AB  - In this paper, an adaptive activity and environment recognition algorithm running
      on a mobile phone is presented. The algorithm makes inferences based on sensor
      and radio receiver data provided by the phone. A wide set of features that can be
      extracted from these data sources were investigated, and a Bayesian maximum a
      posteriori classifier was used for classifying between several user activities
      and environments. The accuracy of the method was evaluated on a dataset collected
      in a real-life trial. In addition, comparison to other state-of-the-art
      classifiers, namely support vector machines and decision trees, was performed. To
      make the system adaptive for individual user characteristics, an adaptation
      algorithm for context model parameters was designed. Moreover, a confidence
      measure for the classification correctness was designed. The proposed adaptation
      algorithm and confidence measure were evaluated on a second dataset obtained from
      another real-life trial, where the users were requested to provide binary
      feedback on the classification correctness. The results show that the proposed
      adaptation algorithm is effective at improving the classification accuracy. 

PMID- 25372622
TI  - Data View: Estimates of Dual and Full Medicaid Benefit Dual Enrollees, 1999.

PMID- 25372621
TI  - PCDD/PCDF ratio in the precursor formation model over CuO surface.
AB  - The discrepancies between polychlorinated dibenzo-p-dioxin to polychlorinated
      dibenzofuran (PCDD to PCDF) ratios in laboratory and field studies in the exhaust
      of combustion sources are not fully explained by available formation models. In
      this paper we present the results of experimental studies of the surface mediated
      formation of PCDD/F at the conditions mimicking the combustion cool zone from a
      mixture of 1,2-dichlorobenzene (1,2-DCBz) and 2-monochlorophenol (2-MCP) over a
      model surface consisting of 5% CuO/Silica. The PCDD to PCDF ratio was found to be
      strongly dependent on the ratio of chlorinated benzenes to chlorinated phenols
      and oxygen content. The higher the 1,2-DCBz to 2-MCP ratio, the lower the PCDD to
      PCDF ratio. PCDFs are formed predominantly from chlorinated benzenes, while
      chlorinated phenols are responsible for majority of PCDDs. These laboratory
      results are in general agreement with full-scale measurement and can be used to
      improve predictive models of PCDD/F formation.

PMID- 25372623
TI  - Association between ADH1C and ALDH2 polymorphisms and alcoholism in a Turkish
      sample.
AB  - BACKGROUND: Polymorphisms in the genes encoding alcohol metabolizing enzymes are
      associated with alcohol dependence. AIM: To evaluate the association between the
      alcohol dehydrogenase 1C (ADH1C) Ile350Val and aldehyde dehydrogenase 2 (ALDH2)
      Glu504Lys polymorphisms and alcohol dependence in a Turkish sample. METHODS: 235
      individuals (115 alcohol-dependent patients and 120 controls) were genotyped for
      ADH1C and ALDH2 with PCR-RFLP (polymerase chain reaction-restriction fragment
      length polymorphism). Association between the polymorphisms and family history,
      daily and maximum amount of alcohol consumed was investigated. The associations
      between alcohol dependence, severity of consumption and family history and the
      polymorphisms were analyzed by chi-square or Fisher's exact test where necessary.
      Relationship between genotypes and dependence related features was evaluated
      using analysis of variance (ANOVA). RESULTS: The -350Val allele for ADH1C
      (ADH1C*2) was increased in alcohol-dependent patients (P = 0.05). In individuals
      with a positive family history, the genotype distribution differed significantly
      (P = 0.031) and more patients carried the Val allele compared with controls (P =
      0.025). Genotyping of 162 participants did not reveal the -504Lys allele in
      ALDH2. CONCLUSIONS: These findings suggest that ADH1C*2 is associated with
      alcohol dependence in the Turkish population displaying a dominant inheritance
      model. ADH1C*2 allele may contribute to the variance in heritability of alcohol
      dependence. The ALDH2 -504Lys/Lys or Glu/Lys genotypes were not present in
      alcohol-dependent patients, similar to that seen in European populations and in
      contrast to the findings in the Asian populations.

PMID- 25372625
TI  - Covering Uninsured Adults Through Medicaid: Lessons from the Oregon Health Plan.
AB  - The Oregon Health Plan (OHP), Oregon's section 1115 Medicaid waiver program,
      expanded eligibility to all residents living below poverty. We use survey data,
      as well as OHP administrative data, to profile the expansion population and to
      provide lessons for other States considering such programs. OHP's eligibility
      expansion has proved a successful vehicle for covering large numbers of uninsured
      adults, although most beneficiaries enroll for only a brief period of time. The
      expansion population, particularly childless adults, is relatively sick and has
      high service use rates. Beneficiaries are also likely to enroll when they are in
      need of care.

PMID- 25372624
TI  - Polymer-based synthetic dendritic cells for tailoring robust and multifunctional
      T cell responses.
AB  - Dendritic cells (DCs) are antigen-presenting cells that play an essential role in
      T cell activation. Recent efforts in cancer immunotherapy have been directed at
      the development of artificial antigen presenting cells (aAPCs) loaded with tumor
      antigens. These aAPCs are designed to mimic DCs with the goal of triggering an
      efficient and specific T cell response directed against the tumor. We have
      designed a novel synthetic dendritic cell (sDC) that possesses the essential
      features of natural DCs. Our sDC is based on a semiflexible poly(isocyano
      peptide) polymer and carries anti-CD3 antibodies (alphaCD3) for triggering the T
      cell receptor/CD3 complex as well as anti-CD28 antibodies (alphaCD28) as a co
      stimulatory signal. Multiple copies of both antibodies facilitate multivalent
      binding similar to natural DCs. The high mobility of these polymer-bound
      antibodies, reminiscent of protein motility in a natural plasma membrane, enables
      receptor rearrangements to occur during T cell activation. We show that our
      bifunctional alphaCD3/alphaCD28-sDC triggers T cell activation at significantly
      lower antibody concentrations than freely soluble antibodies. This superior
      performance is further demonstrated in comparison to a mixture of monofunctional
      alphaCD3-sDC and alphaCD28-sDC. The presence of both antibodies on the same
      polymer not only reduces the threshold for T cell activation but, more
      importantly, critically shapes the specificity of the T cell response.
      alphaCD3/alphaCD28-sDC is a far more efficient activator of multifunctional
      killer cells. These findings demonstrate the potential of multifunctional
      polymers for mimicking natural DCs, paving the way for their exploitation in
      immunotherapeutic strategies.

PMID- 25372626
TI  - Medicare: 35 Years of Service.

PMID- 25372627
TI  - Celebrating 35 Years of Medicare and Medicaid.

PMID- 25372629
TI  - Label-free surface-enhanced Raman scattering imaging to monitor the metabolism of
      antitumor drug 6-mercaptopurine in living cells.
AB  - The molecular processes of drugs from cellular uptake to intracellular
      distribution as well as the intracellular interaction with the target molecule
      are critically important for the development of new antitumor drugs. In this
      work, we have successfully developed a label-free surface-enhanced Raman
      scattering (SERS) technique to monitor and visualize the metabolism of antitumor
      drug 6-mercaptopurine in living cells. It has been clearly demonstrated that
      Au@Ag NPs exhibit an excellent Raman enhancement effect to both 6-mercaptopurine
      and its metabolic product 6-mercaptopurine-ribose. Their different ways to absorb
      at the surface of Au@Ag NPs lead to the obvious spectral difference for
      distinguishing the antitumor drug and its metabolite by SERS spectra. The Au@Ag
      NPs can easily pass through cell membranes in a large amount and sensitively
      respond to the biological conversion of 6-mercaptopurine in tumor cells. The
      Raman imaging can visualize the real-time distribution of 6-mercaptopurine and
      its biotransformation with the concentrations in tumor cells. The SERS-based
      method reported here is simple and efficient for the assessments of drug efficacy
      and the understanding of the molecular therapeutic mechanism of antitumor drugs
      at the cellular level. 

PMID- 25372628
TI  - De novo synthesis and biological evaluation of C6"-substituted C4"-amide
      analogues of SL0101.
AB  - In an effort to improve upon the in vivo half-life of the known ribosomal s6
      kinase (RSK) inhibitor SL0101, C4"-amide/C6"-alkyl substituted analogues of
      SL0101 were synthesized and evaluated in cell-based assays. The analogues were
      prepared using a de novo asymmetric synthetic approach, which featured Pd-pi
      allylic catalyzed glycosylation for the introduction of a C4"-azido group.
      Surprisingly replacement of the C4"-acetate with a C4"-amide resulted in
      analogues that were no longer specific for RSK in cell-based assays. 

PMID- 25372630
TI  - Light-controlled macrocyclization of tetrathiafulvalene with azobenzene:
      designing an optoelectronic molecular switch.
AB  - Macrocyclization between tetrathiafulvalene (TTF) dithiolates and bis
      bromomethylazobenzenes/bis-bromomethylstilbenes is investigated under high
      dilution conditions. We show that macrocycles of different size can be formed
      depending on whether the (Z)- or (E)-isomers of azobenzene (AB) or stilbene are
      used. This represents the first example of a light-controllable cyclization
      reaction. The oxidation potential of the small, structurally rigid TTF-AB
      macrocycle is found to depend on the conformation of the AB moiety, opening the
      way for the modulation of redox properties by an optical stimulus. DFT
      calculations show that the out-of-plane distortion of the TTF moiety in this
      macrocycle is responsible for the variation of its oxidation potential upon
      photoisomerization of the neighboring AB bridge. 

PMID- 25372631
TI  - Embryonic origin and compartmental organization of the external genitalia.
AB  - Genital malformations occur at a high frequency in humans, affecting ~1:250 live
      births. The molecular mechanisms of external genital development are beginning to
      be identified; however, the origin of cells that give rise to external genitalia
      is unknown. Here we use cell lineage analysis to show that the genital tubercle,
      the precursor of the penis and clitoris, arises from two populations of
      progenitor cells that originate at the lateral edges of the embryo, at the level
      of the posterior hindlimb buds and anterior tail. During body wall closure, the
      left and right external genital progenitor pools are brought together at the
      ventral midline, where they form the paired genital swellings that give rise to
      the genital tubercle. Unexpectedly, the left and right external genital
      progenitor pools form two lineage-restricted compartments in the phallus.
      Together with previous lineage studies of limb buds, our results indicate that,
      at the pelvic level, the early lateral mesoderm is regionalized from medial to
      lateral into dorsal limb, ventral limb, and external genital progenitor fields.
      These findings have implications for the evolutionary diversification of external
      genitalia and for the association between external genital defects and disruption
      of body wall closure, as seen in the epispadias-extrophy complex. 

PMID- 25372632
TI  - Structural characterization of environmentally relevant ternary uranyl citrate
      complexes present in aqueous solutions and solid state materials.
AB  - Organic acids are important metal chelators in environmental systems and tend to
      form soluble complexes in aqueous solutions, ultimately influencing the transport
      and bioavailability of contaminants in surface and subsurface waters. This is
      particularly true for the formation of uranyl citrate complexes, which have been
      utilized in advanced photo- and bioremediation strategies for soils contaminated
      with nuclear materials. Given the complexity of environmental systems, the
      formation of ternary or heterometallic uranyl species in aqueous solutions are
      also expected, particularly with Al(iii) and Fe(iii) cations. These ternary forms
      are reported to be more stable in aqueous solutions, potentially enhancing
      contaminant mobility and uptake by organisms, but the exact coordination
      geometries of these soluble molecular complexes have not been elucidated. To
      provide insight into the nature of these species, we have developed a series of
      geochemical model compounds ([(UO(2))(2)Al(2)(C(6)H(4)O(7))(4)](6-) (U(2)Al(2)),
      [(UO(2))(2)Fe(2)(C(6)H(4)O(7))(4)](6-) (U(2)Fe(2)-1) and
      [(UO(2))(2)Fe(2)(C(6)H(4)O(7))(4)(H(2)O)(2)](6-) (U(2)Fe(2)-2) and
      [(UO(2))(2)Fe(4)(OH)(4)(C(6)H(4)O(7))(4)](8-) (U(2)Fe(4))) that were
      characterized by single-crystal X-ray diffraction and vibrational spectroscopy.
      Mass spectroscopy was then employed to compare the model compounds to species
      present in aqueous solutions to provide an enhanced understanding of the ternary
      uranyl citrate complexes that could be relevant in natural systems.

PMID- 25372633
TI  - [Out-of-hospital cardiopulmonary resuscitation needs the ventilation].
AB  - Cardiopulmonary resuscitation (CPR) is series of rescue measures for saving
      cardiac arrest patients. Early initiation and good quality of CPR is crucial for
      increasing chance of survival from out-of-hospital cardiac arrest. In recent
      years, the CPR guidelines have changed a lot, especially in basic life support.
      The guideline now pays more attention on chest compression and less to
      ventilation. CPR with chest compression only and without mouth-to-mouth
      ventilation is more popular. In this article, we outline the development and
      recent researches of CPR. As depriving oxygen from a collapsed patient for 6 min
      may result in poor outcome, the average time for ambulance transport is longer
      (about 10 to 16 min) in China, which makes rescuers easy to feel fatigue, chest
      compression only CPR is not suitable in China. Though non-professional rescuers
      have difficulty to perform mouth-to-mouth ventilation, they generally show a
      willingness to do so. To strengthen public standard CPR training including mouth
      to-mouth ventilation and chest compression, is most important to promote CPR in
      China.

PMID- 25372634
TI  - [Effects of feeding mode on biological clock and circadian expression of lipid
      metabolism-related genes in mice].
AB  - OBJECTIVE: To explore the effects of feeding mode on biological clock and
      circadian expression of lipids metabolism-related genes in mice. METHODS: Ninety
      healthy male ICR mice were divided into 3 groups with 30 in each: ad libitum
      feeding, daytime-feeding and nighttime-feeding groups, in a 12 h to 12 h light
      dark cycle. After two weeks of feeding the animals was sacrificed in batches (5
      in each batch) at 4, 8, 12, 16, 20 and 24 h, the circadian expression of lipids
      metabolism-related genes in the liver and brain was detected by real time
      quantitative RT PCR at 6 time points. RESULTS: The circadian oscillator in the
      brain was more sensitive to alteration of feeding mode than that in the liver,
      nighttime feeding decreased peak mRNA levels of Cry2, Per1, and Per2 (5.5, 4.3
      and 7.1 folds, respectively) in the brain. However, there was no difference in
      the expression rhythm of hepatic clock genes between nighttime-feeding and ad
      libitum group. In addition, changed feeding mode significantly decreased the peak
      value of Rev erbalpha (2 folds for daytime feeding, 3.4 folds for nighttime
      feeding) and Dbp (10.6 folds for daytime feeding, 2.8 folds for nighttime
      feeding), which two had opposite expression mode in different feeding modes.
      Different expression rhythm of lipid metabolism related genes SREBP1-c,
      PPARalpha, FAS, and CPT was shown with decreased mRNA expression levels of SREBP1
      c and PPARalpha in daytime feeding (5.5 folds, 4 folds) and nighttime feeding
      (4.4 folds, 4.8 folds). CONCLUSION: Changing the feeding mode could entrain
      circadian oscillators both in the brain and liver. What is more, hepatic
      circadian oscillators couple with the feeding time.

PMID- 25372635
TI  - [Inhibitory effect of inositol hexaphosphate on proliferation of LNCaP cells and
      its relation to IGFBP 3 expression].
AB  - OBJECTIVE: To investigate the effect of inositol hexaphosphate (IP6) on
      proliferation of human prostate carcinoma LNCaP cells and its relation to insulin
      like growth factors binding protein-3 (IGFBP-3) expression. METHODS: The siRNA
      technology was used to silence the IGFBP-3 gene in LNCaP cells. LNCaP cells and
      IGFBP-3 gene silenced LNCaP cells were exposed to IP6 for 24 h. Cell viability
      was measured by MTT assay; cell cycle arrest and cell apoptosis were detected by
      flow cytometry. The expression levels of IGFBP-3 and Bcl-2 mRNA and protein were
      analyzed by real-time quantitative RT-PCR and Western blotting, respectively.
      RESULTS: The proliferation of LNCaP cells was be inhibited by IP6 in a dose
      dependent manner. After exposure to IP6 for 24 h, the cell viability in LNCaP
      cells and siRNA-treated LNCaP cells was 53.2%+/-11.6% and 82.3%+/-10.9%,
      respectively (P<0.05). After treatment of 1.5 mmol IP6,the apoptosis rate of
      LNCAP cells and siRNA-treated LNCAP cells was 40.48%+/-13.21% and 30.43%+/
      10.65%, respectively (P<0.05). The proportion of G1 and G2 phase in LNCAP cells
      was 70.58%+/-8.25% and 5.64%+/-1.23%,after IP6 treatment the percentage of G1
      phase cells decreased to 48.66%+/-11.23% and G2 phase cells increased to 31.11%+/
      9.68%. However, for siRNA treated LNCAP cells, the proportion of G1 phase cells
      was 58.25%+/-12.36% and G2 phase cells was 23.85%+/-12.45%. Higher expression of
      IGFBP-3 and lower expression of Bcl-2 in LNCaP cells treated with IP6 were found
      at both mRNA and protein levels. IP6 treatment enhanced IGFBP-3 mRNA expression
      by 2.21+/-0.15 folds. In the contrast, expression of Bcl-2 mRNA decreased by
      0.69+/-0.03 folds. Meanwhile, after IGFBP- gene silence Bcl-2 expression was not
      decreased. CONCLUSION: IP6 can inhibit the proliferation of LNCaP cells, which
      may be associated with the changes of IGFBP-3 level through Bcl-2 expression.

PMID- 25372636
TI  - [STC-1 is involved in anti-hypoxia proliferative balance of renal cancer cells by
      down-regulation of intracellular Ca2+ and HIF-1alpha levels].
AB  - OBJECTIVE: To investigate effects of stanniocalcin-1 (STC-1) on proliferation
      balance under hypoxic condition in renal cancer cells and its mechanism. METHODS:
      Hypoxic model was induced on renal cancer GRC-1 cells (Group H), the cells were
      treated with STC-1 protein at concentrations of 0.1 nmol/L (H1), 0.5 nmol/L (H2),
      1.0 nmol/L (H3), or normal saline (H0) for 48 h, respectively. Cells
      proliferation was measured by MTT assay; mRNA and protein expressions of hypoxia
      inducible factor 1alpha (HIF-1alpha) and STC-1 in GRC-1 cells were detected by RT
      PCR and ELISA, respectively; the intracellular levels of Ca2+ and adenosine
      triphosphate (ATP) were determined by fluorescence spectrophotometry and
      spectrophotometry, respectively. RESULTS: The expression of HIF-1alpha, STC-1 and
      Ca2+ levels were increased in GRC-1 cells under hypoxia condition; STC-1 reversed
      these changes in a dose-effect manner. Hypoxia significantly inhibited cell
      proliferation and the generation of ATP in GRC-1 cells and exogenous STC-1
      reversed the effects of hypoxia; ATP generation increased gradually with
      increasing STC-1 concentration, but the cell proliferation was reduced.
      CONCLUSION: Exogenous STC-1 can promote the proliferation of renal cancer cells
      in hypoxia condition by reducing HIF-1alpha expression and Ca2+ content and
      increased ATP production, but the progressive inhibition of HIF-1 alpha hindered
      the renal carcinoma cell proliferation further, which indicates that STC-1 may be
      involved in anti-hypoxia proliferative balance of renal cancer cells.

PMID- 25372637
TI  - [Effect of cerebral X-ray irradiation on learning and memory function in young SD
      rats].
AB  - OBJECTIVE: To investigate the effect of cerebral X-ray irradiation on learning
      and memory function in young rats. METHODS: Fifty-four SD rats aged 35 d were
      randomly divided into 3 groups with 18 in each group: rats in 3-d group and 7-d
      group received X-ray irradiation with a dose of 28.5 mGy/d for 3 d and 7 d,
      respectively; rats in control group received sham X-ray irradiation. Morris water
      maze (MWM) was tested when animals at age of 60 d; then the animals were
      sacrificed and brain samples were taken. The neurodegeneration was observed by
      Fluro-Jade B staining; the expression of N-methyl-aspartate (NMDA) receptors
      subunit 2B (NR2B) and postsynaptic density protein-95 (PSD-95) in the hippocampus
      were analyzed by immunofluorescence and Western blot methods, respectively, and
      ultrastructure of CA1 region was observed with electron microscopy. RESULTS: No
      significant difference in 1-4 d escape latency as shown in MWM test was noted
      between 3d group and control group (P>0.05); while the escape latency in 7d group
      was significantly longer than that in control group (P<0.01). No significant
      differences in lingering in the quadrant and the frequency of passing through the
      original platform between 3-d group and control group (P>0.05), while those in 7
      d group were significantly lower than those in control group (P<0.01). Compared
      to control group, the number of FJB positive cells in 7-d group was increased
      (P<0.01); the expressions of NR2B and PSD-95 in hippocampus CA1 region were also
      increased (P<0.05). The ultrastructure observation in 7-d group showed that the
      synapse structure of some neurons was impaired. CONCLUSION: X-ray irradiation may
      affect learning and memory function of young rats, which is associated with
      overexpression of NR2B and PSD-95 in hippocampal regions.

PMID- 25372638
TI  - [Gelsolin level for prognostic evaluation in patients with critically illness].
AB  - OBJECTIVE: To investigate the changes of plasma gelsolin level in patients with
      critical illness and its application in prognostic evaluation. METHODS: Ninety
      six critically ill patients admitted in ICU of Sichuan Provincial People's
      Hospital from February 2012 to December 2013 were enrolled in the prospective
      cohort study. Plasma gelsolin levels were detected with enzyme linked
      immunosorbent assay (ELISA) at admission (d1), d2, d4 and d8 after admission, and
      also detected in blood samples of 186 healthy subjects as controls. Logistic
      regression model was used to analyze the relationship between the level of plasma
      gelsolin and prognosis of patients. RESULTS: The average levels of plasma
      gelsolin were significantly lower in critically ill patients than those in
      control subjects (F=1986.37, P<0.01). There was significant difference in overall
      level of gelsolin between survival patients and fatal patients (F=16.691,
      P<0.01). APACHE II score was associated with survival outcomes (r=0.489,
      P=0.009); the APACHE II score was significantly higher in fatal patients than
      that in survival patients (29.5+/-7.7 vs 22.1+/-5.7, t=5.375, P<0.01). There was
      a negative correlation between plasma gelsolin levels and fatal outcomes (r=
      0.512, P<0.01). Logistic regression analysis showed that the overall plasma
      gelsolin levels and the last measured level was a prognostic factor for
      critically ill patients (P<0.05). CONCLUSION: Plasma gelsolin levels are
      correlated with the severity of critically ill patients, and plasma gelsolin can
      be used as indicator of prognosis.

PMID- 25372639
TI  - [The association between body mass index and non-alcoholic fatty liver disease].
AB  - OBJECTIVE: To investigate the association of body mass index (BMI) with alcoholic
      fatty liver disease (NAFLD). METHODS: A cohort of 725 adult subjects underwent
      general health check-up at our hospital in July 2008, then were followed up in
      2011. The clinical data including body mass index(BMI), blood pressure, lab
      testing results and liver ultrasonic findings were retrospectively analyzed. The
      NAFLD was diagnosed according to the guidelines for management of nonalcoholic
      fatty liver disease: an updated and revised edition in 2010 based on liver
      ultrasound results. The risk factors for NAFLD were analyzed with multivariate
      logistic regression. RESULTS: One hundred and sixty two NAFLD cases and 563 non
      NAFLD cases were found in 2008 check-up. Among 563 non-NAFLD subjects, NAFLD was
      developed in 132 (23.4%) at follow-up in 2011. The incidence of NAFLD was
      correlated with the baseline BMI (chi2=82.861,P<0.01). Multivariate logistic
      regression analysis showed that baseline BMI,systolic blood pressure, alanine
      aminotransferase and the increase of BMI were the independent risk factors, while
      high density lipoprotein-cholesterol (HDL-C) was the protective factor for the
      development of NAFLD. Among 162 NAFLD cases, 71 (43.8%) had no evidence of NAFLD
      at the second check-up in 2011. The remission of NAFLD was negatively correlated
      with baseline BMI (chi2=22.425,P<0.01). Multivariate logistic regression analysis
      showed that male sex, baseline BMI and the increase of BMI were negatively
      associated with remission of NAFLD, while the age was positively associated with
      the remission of NAFLD. CONCLUSION: The development and remission of NAFLD are
      frequently encountered in health check-up subjects, which are closely related to
      baseline BMI and changes of BMI during the follow-up.

PMID- 25372640
TI  - [Construction of three HLA-A*0201-peptide tetramers and their preliminary
      application in detection of vitiligo-specific cytotoxic T lymphocytes].
AB  - OBJECTIVE: To construct vitiligo-specific HLA-A*0201-peptide tetramers and to
      apply the constructed tetramers in detection of vitiligo-specific cytotoxic T
      lymphocytes (CTL). METHODS: Proteins HLA-A0201*-BSP and beta2M were obtained by
      effective prokaryotic expression. The purified proteins were refolded with
      vitiligo antigen peptides MelanA 26-35, gp100 209-217, and tyrosinase 1-9,
      respectively to form HLA-A*0201-peptide complex. The complex was biotinylated by
      BirA enzyme and purified by gel-filtration chromatography. The tetramers were
      generated by mixing the complex with phycoerythrin (PE)-streptavidin at a ratio
      of 4?1 and identified by Dot-blot assay. The capacity of tetramer to detect
      vitiligo-specific CTL was analyzed by flow cytometry. RESULTS: The biotinylation
      of vitiligo-specific HLA-A*0201-peptide tetramers were successfully performed by
      Dot-blot. Flow cytometry analysis indicated that the tetramer effectively bound
      to specific CTL from peripheral blood of patients with vitiligo. CONCLUSION:
      Three kinds of biotinylated vitiligo-specific HLA-A*0201-peptide tetramers have
      been constructed successfully. The tetramer can detect antigen specific CTL from
      patients with vitiligo.

PMID- 25372641
TI  - [Roles of PIK3R1 gene in development of hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the roles of phosphatidylinositol 3 kinase regulatory
      subunit alpha (PIK3R1)gene in the development of hepatocellular carcinoma (HCC).
      METHODS: Surgical specimens of liver cancer and corresponding pericancerous liver
      tissue were collected from 20 patients with hepatocellular carcinoma. Expression
      of p85alpha, encoded by PIK3R1, in HCC tissue specimens was detected by Western
      blotting and immunohistochemistry. HCC HepG2 cells were transfected with PIK3R1
      siRNA or PIK3R1-cDNA. The expression of PIK3R1 in transfected HepG2 cells or
      control cells were detected by real-time PCR. Cell proliferation was evaluated by
      MTT, colony formation assays and flow cytometry respectively. The expression of
      PI3K/AKT pathway-related proteins were detected by Western blotting. RESULTS: The
      expression of p85alpha in liver tissue was higher than that in pericancerous
      tissues (1.27+/-0.58 vs 0.99+/-0.47,t=-3.25,P<0.05). The expression of PIK3R1 was
      decreased by 0.19+/-0.03 fold in PIK3R1siRNA-transfected HepG2
      cells(t=46.77,P<0.05),and increased by 32.36+/-3.33 fold in PIK3R1 cDNA 
      transfected cells(t=-16.31, P<0.05). MTT result showed that PIK3R1 siRNA
      inhibited growth of HepG2 cells (0.611+/-0.072 vs 0.807+/
      0.059,t=3.65,P<0.05),while PIK3R1 cDNA increased the cell growth(0.937+/-0.060 vs
      0.693+/-0.065,t=-4.78,P<0.05). PIK3R1 siRNA transfected cells presented lower
      colony-forming efficiency than control group(3.8%+/-0.84% vs 15.0%+/
      2.3%,t=7.92,P<0.05),while PIK3R1 cDNA transfected cells had higher colony-forming
      efficiency than control group (23.6%+/-3.4% vs 12.0%+/-1.5%,t=-5.40,P<0.05).
      PIK3R1 siRNA reduced the ratio of S phase cells(13.9%+/-0.015% vs 32.9%+/
      0.07%,t=45.97,P<0.01, while PIK3R1 cDNA increased S phase cells(56.33%+/-0.024%
      vs 31.94%+/-0.042%,t=-8.73,P<0.01). PIK3R1 increased the level of p-AKT and
      decreased p53 level. CONCLUSION:p85alpha is highly expressed in HCC,and PIK3R1
      gene may promote proliferation of HepG2 cells by activating PI3K/AKT pathway.

PMID- 25372642
TI  - [Assessment of left ventricular twist in type 2 diabetes mellitus by using two
      dimensional ultrasound speckle tracking imaging].
AB  - OBJECTIVE: To evaluate the left ventricular twist characteristics in patients
      with type 2 diabetes by using two-dimensional speckle tracking imaging (STI).
      METHODS: Ninety-three patients with type 2 diabetes admitted in Zhejiang Hospital
      from May 2012 to September 2013 were enrolled. According to left ventricular
      ejection fraction (LVEF), patients were divided into two groups: normal left
      ventricular systolic function group (group A, LVEF>=0.50, n=46) and abnormal left
      ventricular systolic function group (group B, LVEF <0.50, n=47). Forty-six
      healthy subjects were selected as normal controls. STI was applied to
      quantitatively analyze the left ventricular twist. Correlation of the peak of
      left ventricular twist angle (Peaktw), aortic valve closure time twist angle
      (AVCtw), and mitral valve opening time twist angle (MVOtw) with LVEF, Tei index,
      E/A, and E/e was evaluated. Consistency check for STI was conducted to assess its
      stability and reliability. RESULTS: The Peaktw, AVCtw, and MVOtw in group A were
      significantly elevated than those in normal controls (P<0.05). The Peaktw, AVCtw,
      and MVOtw in group B was lower than those in normal controls and group A
      (P<0.05). In diabetic patients, the Peaktw, AVCtw, MVOtw were positively
      correlated with LVEF (r=0.968, 0.966, 0.938;P<0.05) and E/A (r=0.798, 0.790,
      0.788; P<0.05), and were negatively correlated with Tei index (r=-0.834, -0.811, 
      0.797; P<0.05) and E/e (r=-0.823, -0.805, -0.771; P<0.05). The agreement between
      measurers and within measurers of Peaktw was satisfactory (between measurers:
      R=0.957, bias=-0.1, 95% consistency limit=-2.8-2.7; within measurer: R=0.964,
      bias=-0.2, 95% consistency limits=-2.7-2.2). CONCLUSION: STI can be used for
      early recognition of abnormal changes of cardiac function in type 2 diabetic
      mellitus patients, with high stability and reliability.

PMID- 25372643
TI  - [Application of three dimensional model in treatment of superolateral dislocation
      of mandibular condyle].
AB  - OBJECTIVE: To assess the application of three-dimensional jaw model in treatment
      of superolateral dislocation of condyle. METHODS: Nine patients with
      superolateral dislocation of condyle and symphyseal fractures were admitted in
      hospital from June 2008 to June 2013. Spiral CT scan on maxilla and mandible was
      performed,and three-dimensional jaw model was constructed with rapid prototyping
      technology. According to conditions of condylar superolateral dislocation
      model,the operation scheme was designed. The symphyseal fracture line was made
      and fracture was reduced on three-dimensional jaw model. Individualized
      prefabricated reconstructive titanium plate was made on symphyseal fracture
      model. Symphyseal fracture was replaced with individualized prefabricated
      mandibular reconstruction titanium plate according to occlusal relationship. At
      the same time,reduction of condylar superolateral dislocation was accomplished.
      RESULTS: Operations were successfully completed in 9 cases under guidance of
      three dimensional jaw model surgery. Operative incision was primarily healed,and
      occlusal relationship was restored. Postoperative CT scan showed that the
      locations of condyle in 9 cases were completely restored. Patients were followed
      up for 6-28 months with a median of 18 months. The maximum of mouth opening was
      3.1- 4.2 cm with a medians of 3.3 cm,and the occlusal relationship of all
      patients was normal after surgery. CONCLUSION: Three-dimensional jaw model can
      show complete status of condylar superolateral dislocation and symphyseal
      fracture. The model can accurately shape symphyseal reconstructive titanium plate
      and restore condylar superolateral dislocation during reductive surgery.

PMID- 25372644
TI  - [Treatment of distal clavicle type II fracture: suture anchor versus clavicular
      hook plate].
AB  - OBJECTIVE: To compare the efficacy of suture anchor with clavicular hook plate in
      treatment of type II fractures of the distal clavicle. METHODS: Forty patients
      with Neer type II fractures of distal clavicle were treated in our hospital from
      May 2009 to May 2010, including 21 cases treated with suture anchors and 19 cases
      treated with clavicular hook plate. The time of fracture union and Constant
      Murley scores were compared between two groups. RESULTS: All incisions reached
      primary healing, and there was no infection or hematoma formation. Postoperative
      follow-up time was 12-24 months, mean 14.5 months. The mean time of fracture
      reunion in suture anchors group was 13.2+/-2.0 weeks (9-17 weeks) and that in
      clavicular hook plate group was 13.3+/-2.0 weeks (10-16 weeks, P>0.05). The mean
      postoperative Constant Murley scores in suture anchors and hook plate groups were
      (91.1+/-6.5)% and (89.2+/-7.6)%, respectively (P>0.05). But the pain score in
      suture anchor group was higher than that in hook plate group (12.6+/-1.9 vs
      11.3+/-2.3, P<0.05). CONCLUSION: Compared with claviculer hook plate, the suture
      anchor has good clinical results and less complications in treatment of type II
      fractures of distal clavicle.

PMID- 25372645
TI  - [Bilateral middle cerebellar peduncle infarcts caused by bilateral vertebral
      artery occlusion: a case report].
AB  - Patients with bilateral vertebral artery occlusion have a high incidence of
      cerebral infarction with poor prognosis. Infarction of bilateral middle
      cerebellar peduncle (MCP) is extremely rare and only a few cases have been
      reported in literature. A 74-year-old male patient was admitted to our hospital
      with a chief complaint of dizziness and walking instability for 13 d. Brain
      magnetic resonance image showed acute bilateral middle cerebellar peduncle
      infarction. Digital subtraction angiography showed occlusion of the initiation
      part of left vertebral artery and whole right vertebral artery, while a large
      amount of collateral circulations and recanalization were observed. After volume
      expansion, anti-platelet aggregation and lipid-lowering therapy, the symptoms
      disappeared. The patient was followed up for 10 months and he recovered well. 

PMID- 25372646
TI  - [Adult Sturge-Weber syndrome without facial hemangioma: report of one case].
AB  - Sturge-Weber syndrome (SWS) is characterized by angiomas affecting the ophthalmic
      division of the trigeminal nerve, epilepsy, intellectual impairment, hemiplegia
      and glaucoma. We report a patient who developed SWS without facial hemangioma
      (SWS type III) in his adulthood. The patient presented with repeated episodes of
      headache since age 37 year. He manifested first attack of seizure at the age 47
      year followed by aphasia and right upper limb palsy. Brain CT scan revealed right
      parietal-occipital calcification, brain CT angiography showed right temporal lobe
      and occipital lobe vascular malformation, and MRI showed leptomeningeal
      enhancement in the riht cerebral piamater. The seizure was controlled with
      antiepileptic drugs and reviewed in routine follow up.

PMID- 25372647
TI  - [Totally laparoscopic versus laparoscopic assisted distal gastrectomy for gastric
      cancer: a meta-analysis].
AB  - OBJECTIVE: To compare the safety and efficacy of totally laparoscopic distal
      gastrectomy (TLDG) with laparoscopic assisted distal gastrectomy (LADG) for
      gastric cancer by meta-analysis. METHODS: The literature on comparative studies
      of TLDG and LADG up to June 2014 were extensively retrieved from database PubMed,
      Cochrane library, Web of Science, and Biosis Previews. The operation time, blood
      loss, time to flatus, time to first oral intake, postoperative hospital stay,
      postoperative morbidity, times of analgestic requirement, pain score, and the
      level of C-reactive protein (CRP) on postoperative day 1 and 7 were analyzed. The
      statistical analysis was performed with RevMan 5.1 software. RESULTS: Seven
      studies met the inclusion criteria for meta-analysis. A total of 1783 Patients
      were included for meta-analysis, among whom 727 cases underwent TLDG and 1056
      underwent LADG. Comparing with LADG, TLDG experienced less blood loss [weighted
      mean difference (WMD)=22.86 ml,95% confidence interval (CI): 12.0-33.72,
      P<0.01)], less times of analgesic requirement (WMD=0.58, 95% CI: 0.35-0.81, P<
      0.01),less pain score on postoperative day 1 and day 3 (day1: WMD=0.60, 95% CI:
      0.20-0.99, P < 0.01; day3: WMD=0.36, 95% CI: 0.24-0.48, P < 0.01), earlier
      beginning to take diet (WMD=0.66, 95% CI: 0.13-1.19, P=0.01). The operation time,
      postoperative hospital stay, overall morbidity and anastomosis-related morbidity,
      and the level of CRP on postoperative day 1 and 7 were similar between two groups
      (Ps>0.05). CONCLUSION: TLDG is a safe and feasible procedure with less blood
      loss, less pain, and quicker recovery than those of LADG.

PMID- 25372648
TI  - [Association between androgenetic alopecia and metabolic syndrome: a meta
      analysis].
AB  - OBJECTIVE: To investigate the association between androgenetic alopecia (AGA) and
      metabolic syndrome (MS). METHODS: Literature on association between AGA and MS up
      to December 26, 2013 was searched from PubMed, Web of Knowledge, Scopus,
      Cochrance library, SinoMed, CNKI, Wanfang and VIP databases, and the studies met
      the eligibility criteria were selected. Meta-analysis was performed by using
      StataSE 12.0 software to determine the association between AGA and MS. RESULTS:
      Four case-control studies and 2 cross-sectional studies met the eligibility
      criteria, including 950 AGA subjects and 3056 control subjects were entered the
      analysis. Meta-analysis showed that AGA was significantly correlated with MS
      (OR=2.70, 95%CI: 1.67-4.37, P<0.01). Stratification analysis showed that AGA was
      significantly correlated with MS in male (OR=2.30, 95%CI: 1.33-3.98, P<0.01) and
      female subjects (OR=4.61, 95%CI: 1.26-16.94, P<0.05); and AGA was significantly
      correlated with MS in European (OR=5.29, 95%CI: 2.86-9.80, P<0.01) and Asian
      subjects (OR=1.92, 95%CI: 1.18-3.10, P<0.01). CONCLUSION: Based on the available
      data, AGA may be a risk factor for MS, indicating that AGA patients would be a
      targeting population for screening of metabolic syndrome.

PMID- 25372649
TI  - [Progress in the effects of BRAP gene on cardiovascular diseases].
AB  - BRAP (BRCA1 associated protein) is one of BRCA1 (Breast cancer suppressor
      protein) associated cytoplasmic proteins. BRAP gene has been found to be
      associated with the risk of some cancers, and the associations between BRAP and
      cardiovascular diseases and metabolic syndrome is gradually attracting much
      attention. However, the explicit mechanisms involved remain to be fully
      elucidated. We reviewed the association between BRAP gene and cardiovascular
      diseases and metabolic syndromes and the biologic mechanisms in the regulation of
      metabolism, hoping to provide clues on our future researches. 

PMID- 25372650
TI  - [Roles of long noncoding RNA in lung cancer].
AB  - Long noncoding RNAs are a group of noncoding RNAs with a length more than 200
      nucleotides. Recent studies have revealed that long noncoding RNAs play an
      important role in the development and progression of cancer. Lung cancer is the
      leading cause of cancer-related death all over the world. In this article, we
      review the roles of long noncoding RNAs in lung cancer to provide new insights
      into the diagnosis and treatment of the disease.

PMID- 25372651
TI  - [Progress on genetic basis of primary aldosteronism].
AB  - It has been proven that familial aldosteronism type I is related to 11-beta
      hydroxylase (CYP11B1)/aldosterone synthase (CYP11B2) chimeric genes. In recent
      years, accumulated evidences indicate that the genetic basis of primary
      aldosteronism may involve chromosome 7p22 candidate genes, polymorphisms of
      CYP11B1 and CYP11B2 genes, mutations of ion channel- related KCNJ5, ATP1A1,
      CACNA1D genes. The article reviews the progress on genetic basis of primary
      aldosteronism. 

PMID- 25372652
TI  - Effects of anions on the electrodeposition of cobalt on pt(111) electrode.
AB  - Voltammetry and in-situ scanning tunneling microscopy (STM) were used to examine
      electrodeposition of cobalt (Co) on a stationary Pt(111) electrode in 0.1 M K2SO4
      + 1 mM H2SO4 + 10 mM CoSO4 (or the sulfate solution) without and with 10 mM
      chloride (the chloride solution). Under- and overpotential deposition (UPD and
      OPD) of Co resulted in reduction peaks at -0.52 and -0.74 V (vs Ag/AgCl),
      respectively. Hydrogen evolution was the major obstruction to Co(2+) reduction,
      which limited the efficiency of Co deposition at ~63% in both solutions. UPD of
      Co resulted in a highly ordered honeycomb structure in the sulfate solution,
      whereas that formed in the chloride solution was clearly disordered. Multilayer
      Co deposit formed by OPD at -0.74 V in the sulfate medium was crystalline,
      forming moire structures for the first eight layers, followed by pyramids made of
      stacked triangles. These results suggested face-centered cubic stacking of the Co
      deposit. Co film produced in the chloride solution was also layered, except
      perimeters of Co layers were mostly rugged. Distinct screw dislocations and
      spiral defects were seen in the Co thin films produced in both solutions. 

PMID- 25372653
TI  - [Contract Conditions for GPs in Training while Working in Ambulatory Care].
AB  - BACKGROUND: In Germany, the situation of GPs in training has received growing
      attention. Central funding of GPs in training who are working in ambulatory care
      has been increased up to 3 500 Euros/month. However, the contract conditions of
      GPs in training who are working in ambulatory care have been unknown as yet.
      METHODS: An online survey was undertaken. We recruited GPs in training by
      snowball sampling making use of national and local organisations of GPs and GPs
      in training. Our questionnaire consisted of questions concerning sociodemographic
      variables, gross wage, working hours, holidays and free days for educational
      purposes. Data were analysed by descriptive statistical methods. RESULTS: 152
      participants fulfilled the inclusion criteria. 127 were full time GPs in
      training. The median of gross wage was 3 500 Euros/month, the mean gross wage was
      3 878 Euros/month. The gross wage per hour was lower than that for GPs in
      training who are working in hospitals. Especially part time GPs in training had a
      lower gross wage per hour. One third of the GPs in training had no free days for
      educational purposes. More than half of the GPs in training had a weekly meeting
      with their supervisor, however, more than one third of GPs in training had no or
      only irregular meetings with their supervisor. CONCLUSIONS: In Germany, GPs in
      training earn in ambulatory care less than in hospital care. They do not have
      sufficient free days for educational purposes and often there is a lack of
      supervision. This seems to indicate that GPs in training are mainly considered as
      cheap coworkers instead of trainees.

PMID- 25372654
TI  - [Characteristics of Health-Care Provision for Patients in Out-of-Hours Care and
      Regular Care].
AB  - BACKGROUND: Little is known of the primary care characteristics in out of hours
      care centres (OOHC) as compared to regular care in Germany. Obviously the
      provision of patients in OOHC exhibits special characteristics concerning supply
      requirements, occupation and physician services, that require a first
      approximation. METHODS: The data retrieval is managed within the CONTENT
      (CONTinous morbidity registration Epidemiologic NeTwork) research network. The
      used software allows for classifying reasons for encounter (RFE), health-problems
      (diagnoses) and processes of care (prescriptions, referrals, hospitalisations)
      with the International Classification of Primary Care (ICPC). Furthermore the
      software allows for pseudonymised data export. One OOHC Centre in South Hessen is
      part of the network. Therefore, this allows the comparison of this OOHC centre
      with the regular care of the included 5 physicians in 4 practices of the same
      region. RESULTS: A 3-year period (01 April 2010-31 March 2013) with 192,827
      patient contacts of 13,394 patients (58.1% female) in regular care and 14,354
      patient contacts with 9,208 patients (64.1% female) in OOHC was described. Medium
      age of the patients of the regular provision was 59.6 vs. 45.7 years in the OOHC
      centre based on the contacts (p<0.0001). The most frequent RFE in the OOHC centre
      were fever and pain predominantly caused by acute infections, injuries or acute
      pain of the musculoskeletal system. In regular care there could be documented
      predominantly chronic health issues and vaccinations. The prevalent prescriptions
      in OOHC were therefore antibiotics and analgesics in regular care blood pressure
      medication and antidiabetic drugs. The rate of referrals was obviously lower than
      in regular care (7.1 vs. 22.7; p<0.0001), whereas the rate of hospitalisations
      was obviously higher in OOHC than in regular care (5.6 vs. 1.1; p<0.0001).
      CONCLUSION: With the help of the data, requirements, occupation, resulting
      diagnoses and care processes in regular and out of hours care can be compared and
      described in detail. We could document major differences between the provision in
      OOHC and regular care. The results encourage initiating further studies to ensure
      the supply of primary care in OOHC.

PMID- 25372655
TI  - [On the economic burden of MRSA in Germany].
AB  - INTRODUCTION: Methicillin-resistant S. aureus (MRSA) usually exhibits resistance
      not only against beta-lactam antibiotics but also against other classes of
      antibiotics with the result that infections caused by this bacterium are
      difficult to treat. Due to additional morbidity and mortality a high economic
      burden can be expected. AIM: The aim of this study was to outline the cost
      effects caused by MRSA colonisation and infections and to quantify the annual
      economic burden in Germany by using published data in order to assess the costs
      due to MRSA in Germany. METHODS: Based on the available literature we estimated
      tangible and intangible costs per patient associated with MRSA. Total costs were
      calculated using data of the MRSA-KISS and the Federal Bureau of Statistics as
      well as other prevalence data. These costs are shown in prices of the year 2011.
      RESULTS: Direct costs occurring in German hospitals are estimated to be between
      354.29 million ? and 1.55 billion ?. Productivity losses due to an extended
      duration of disease are evaluated to be at least 92.77 million ? while lost
      quality adjusted life years due to MRSA infections are estimated at 0.292 * t per
      infected patient (where t denotes the time of the associated health impairment).
      CONCLUSION: It is not possible to quantify the total cost of illness caused by
      MRSA in Germany due to a lack of data on some of the direct costs (e. g., in
      rehabilitation facilities) as well as on the indirect and intangible costs.
      Nevertheless it can be shown that colonisation and infections caused by MRSA
      impose high costs on the health-care system and the whole economy as well.

PMID- 25372656
TI  - Formation of carbon nanosheets via simultaneous activation and catalytic
      carbonization of macroporous anion-exchange resin for supercapacitors
      application.
AB  - Two-dimensional mesoporous carbon nanosheets (CNSs) have been prepared via
      simultaneous activation and catalytic carbonization route using macroporous anion
      exchange resin (AER) as carbon precursor and ZnCl2 and FeCl3 as activating agent
      and catalyst, respectively. The iron catalyst in the skeleton of the AER may lead
      to carburization to form a sheetlike structure during the carbonization process.
      The obtained CNSs have a large number of mesopores, a maximum specific surface
      area of 1764.9 m(2) g(-1), and large pore volume of 1.38 cm(3) g(-1). As an
      electrode material for supercapacitors application, the CNSs electrode possesses
      a large specific capacitance of 283 F g(-1) at 0.5 A g(-1) and excellent rate
      capability (64% retention ratio even at 50 A g(-1)) in 6 mol L(-1) KOH.
      Furthermore, CNSs symmetric supercapacitor exhibits specific energies of 17.2 W h
      kg(-1) at a power density of 224 W kg(-1) operated in the voltage range of 0-1.8
      V in 0.5 mol L(-1) Na2SO4 aqueous electrolyte, and outstanding cyclability
      (retains about 96% initial capacitance after 5000 cycles).

PMID- 25372657
TI  - Problem adaptation therapy for older adults with major depression and cognitive
      impairment: a randomized clinical trial.
AB  - IMPORTANCE: Problem adaptation therapy (PATH) is a treatment for older adults
      with major depression, cognitive impairment (from mild cognitive deficits to
      moderate dementia), and disability. Antidepressants have limited efficacy in this
      population and psychosocial interventions are inadequately investigated.
      OBJECTIVE: To test the efficacy of 12-week PATH vs supportive therapy for
      cognitively impaired patients (ST-CI) in reducing depression and disability in 74
      older adults with major depression, cognitive impairment, and disability. DESIGN,
      SETTING, AND PARTICIPANTS: A randomized clinical trial at the Weill Cornell
      Institute of Geriatric Psychiatry from April 1, 2006, to September 31, 2011.
      Interventions were administered at the participants' homes. Participants included
      74 older individuals (age >= 65 years) with major depression and cognitive
      impairment to the level of moderate dementia. They were recruited through
      collaborating community agencies of Weill Cornell Institute of Geriatric
      Psychiatry and were randomly assigned to 12 weekly sessions of PATH or ST-CI
      (14.8% attrition rate). INTERVENTIONS: Home-delivered PATH vs home-delivered ST
      CI. Problem adaptation therapy integrates a problem-solving approach with
      compensatory strategies, environmental adaptations, and caregiver participation
      to improve patients' emotion regulation. Supportive therapy for cognitively
      impaired patients focuses on expression of affect, understanding, and empathy.
      MAIN OUTCOMES AND MEASURES: Mixed-effects models for longitudinal data compared
      the efficacy of PATH with that of ST-CI in reducing depression (Montgomery-Asberg
      Depression Rating Scale) and disability (World Health Organization Disability
      Assessment Schedule II) during 12 weeks of treatment. RESULTS: Participants in
      PATH had significantly greater reduction in depression (Cohen d, 0.60; 95% CI,
      0.13-1.06; treatment * time, F(1,179) = 8.03; P = .005) and disability (Cohen d,
      0.67; 95% CI, 0.20-1.14; treatment * time, F(1,169) = 14.86; P = .001) than ST-CI
      participants during the 12-week period (primary outcomes). Furthermore, PATH
      participants had significantly greater depression remission rates than ST-CI
      participants (37.84% vs 13.51%; chi(2) = 5.74; P = .02; number needed to treat =
      4.11) (secondary outcome). CONCLUSIONS AND RELEVANCE: Problem adaptation therapy
      was more efficacious than ST-CI in reducing depression and disability. Problem
      adaptation therapy may provide relief to a large group of depressed and
      cognitively impaired older adults who have few treatment options. TRIALS
      REGISTRATION: Clinicaltrials.gov Identifier: NCT00368940.

PMID- 25372659
TI  - Self-assembled graphene oxide microcapsules with adjustable permeability and yolk
      shell superstructures derived from atomized droplets.
AB  - GO microcapsules were assembled on the surface of atomized droplets prepared by a
      spray-drying strategy. The nanochannels in the microcapsule wall can be adjusted
      by water-soluble polymers and make the microcapsule exhibit sustained release.
      The strategy can further be employed to encapsulate metal organic frameworks to
      obtain MOF-GO yolk-shell superstructures. 

PMID- 25372658
TI  - Clinical presentation of patients with Ebola virus disease in Conakry, Guinea.
AB  - BACKGROUND: In March 2014, the World Health Organization was notified of an
      outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread
      to the capital, Conakry, and to neighboring countries and has subsequently become
      the largest epidemic of Ebola virus disease (EVD) to date. METHODS: From March 25
      to April 26, 2014, we performed a study of all patients with laboratory-confirmed
      EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included
      patient characteristics, complications, treatments, and comparisons between
      survivors and nonsurvivors. RESULTS: Of 80 patients who presented with symptoms,
      37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38
      years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%)
      were health care workers; among the health care workers, nosocomial transmission
      was implicated in 12 patients (32%). Patients with confirmed EVD presented to the
      hospital a median of 5 days (interquartile range, 3 to 7) after the onset of
      symptoms, most commonly with fever (in 84% of the patients; mean temperature,
      38.6 degrees C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart
      rate, >93 beats per minute). Of these patients, 28 (76%) were treated with
      intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died,
      with a median time from symptom onset to death of 8 days (interquartile range, 7
      to 11). Patients who were 40 years of age or older, as compared with those under
      the age of 40 years, had a relative risk of death of 3.49 (95% confidence
      interval, 1.42 to 8.59; P=0.007). CONCLUSIONS: Patients with EVD presented with
      evidence of dehydration associated with vomiting and severe diarrhea. Despite
      attempts at volume repletion, antimicrobial therapy, and limited laboratory
      services, the rate of death was 43%.

PMID- 25372660
TI  - Scalable fracture-free SiOC glass coating for robust silicon nanoparticle anodes
      in lithium secondary batteries.
AB  - A variety of silicon (Si) nanostructures and their complex composites have been
      lately introduced in the lithium ion battery community to address the large
      volume changes of Si anodes during their repeated charge-discharge cycles.
      Nevertheless, for large-scale manufacturing it is more desirable to use
      commercial Si nanoparticles with simple surface coating. Most conductive coating
      materials, however, do not accommodate the volume expansion of the inner Si
      active phases and resultantly fracture during cycling. To overcome this chronic
      limitation, herein, we report silicon oxycarbide (SiOC) glass as a new coating
      material for Si nanoparticle anodes. The SiOC glass phase can expand to some
      extent due to its active nature in reacting with Li ions and can therefore
      accommodate the volume changes of the inner Si nanoparticles without
      disintegration or fracture. The SiOC glass also grows in the form of nanocluster
      to bridge Si nanoparticles, thereby contributing to the structural integrity of
      secondary particles during cycling. On the basis of these combined effects, the
      SiOC-coated Si nanoparticles reach a high reversible capacity of 2093 mAh g(-1)
      with 92% capacity retention after 200 cycles. Furthermore, the coating and
      subsequent secondary particle formation were produced by high-speed spray
      pyrolysis based on a single precursor solution. 

PMID- 25372661
TI  - Involvement of TRPV1 and AQP2 in hypertonic stress by xylitol in odontoblast
      cells.
AB  - AIM: To examine the responses of mouse odontoblast-lineage cell line (OLC)
      cultures to xylitol-induced hypertonic stress. METHODOLOGY: OLCs were treated
      with xylitol, sucrose, sorbitol, mannitol, arabinose and lyxose. Cell viability
      was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      assay. The expression of transient receptor potential vanilloids (TRPV) 1, 3 and
      4 was detected using a reverse transcriptase-polymerase chain reaction (RT-PCR)
      assay. The expression of aquaporin (AQP) 2 was detected using immunofluorescence
      and Western blotting analysis. The expression of interleukin-6 (IL-6) under
      xylitol-induced hypertonic stress was assessed using an enzyme-linked
      immunosorbent assay (ELISA). Small interfering ribonucleic acid (siRNA) for AQP-2
      was used to inhibition assay. RESULTS: Xylitol-induced hypertonic stress did not
      decrease OLC viability, unlike the other sugars tested. OLCs expressed TRPV1, 3
      and 4 as well as AQP2. Xylitol inhibited lipopolysaccharide (LPS)-induced IL-6
      expression after 3 h of hypertonic stress. TRPV1 mRNA expression was upregulated
      by xylitol. Costimulation with HgCl2 (AQP inhibitor) and Ruthenium red (TRPV1
      inhibitor) decreased cell viability with xylitol stimulation. OLCs treated with
      siRNA against TRPV1 exhibited decreased cell viability with xylitol stimulation.
      CONCLUSION: OLCs have high-cell viability under xylitol-induced hypertonic
      stress, which may be associated with TRPV1 and AQP2 expressions.

PMID- 25372662
TI  - Identification of novel single nucleotide polymorphisms associated with acute
      respiratory distress syndrome by exome-seq.
AB  - Acute respiratory distress syndrome (ARDS) is a lung condition characterized by
      impaired gas exchange with systemic release of inflammatory mediators, causing
      pulmonary inflammation, vascular leak and hypoxemia. Existing biomarkers have
      limited effectiveness as diagnostic and therapeutic targets. To identify disease
      associating variants in ARDS patients, whole-exome sequencing was performed on 96
      ARDS patients, detecting 1,382,399 SNPs. By comparing these exome data to those
      of the 1000 Genomes Project, we identified a number of single nucleotide
      polymorphisms (SNP) which are potentially associated with ARDS. 50,190SNPs were
      found in all case subgroups and controls, of which89 SNPs were associated with
      susceptibility. We validated three SNPs (rs78142040, rs9605146 and rs3848719) in
      additional ARDS patients to substantiate their associations with susceptibility,
      severity and outcome of ARDS. rs78142040 (C>T) occurs within a histone mark
      (intron 6) of the Arylsulfatase D gene. rs9605146 (G>A) causes a deleterious
      coding change (proline to leucine) in the XK, Kell blood group complex subunit
      related family, member 3 gene. rs3848719 (G>A) is a synonymous SNP in the Zinc
      Finger/Leucine-Zipper Co-Transducer NIF1 gene. rs78142040, rs9605146, and
      rs3848719 are associated significantly with susceptibility to ARDS. rs3848719 is
      associated with APACHE II score quartile. rs78142040 is associated with 60-day
      mortality in the overall ARDS patient population. Exome-seq is a powerful tool to
      identify potential new biomarkers for ARDS. We selectively validated three SNPs
      which have not been previously associated with ARDS and represent potential new
      genetic biomarkers for ARDS. Additional validation in larger patient populations
      and further exploration of underlying molecular mechanisms are warranted. 

PMID- 25372663
TI  - Electrophoretic separation of alginic sodium diester and sodium hexametaphosphate
      in chondroitin sulfate that interfere with the cetylpyridinium chloride titration
      assay.
AB  - The most commonly used chondroitin sulfate (CS) assay method is cetylpyridinium
      chloride (CPC) titration. Cellulose acetate membrane electrophoresis (CAME) is
      the technique used for detection of impurities in the U.S. Pharmacopeia's CS
      monograph. Because CPC titration is a relatively nonspecific quantitative
      technique, the apparent amount of CS as determined by CPC titration alone may not
      reflect the true amount of CS due to possible interference with the CPC assay by
      impurities that contain CPC titratable functional groups. When CAME is used in
      conjunction with CPC titration, certain non-CS and adulterants can be visualized
      and estimated, and a true value for CS can be assigned once the presence of these
      non-CS impurities has been ruled out. This study examines conjunct application of
      CPC and CAME in ascertaining CS assay and purity in the presence of certain
      adulterants. These include propylene glycol alginate sulfate sodium, known in
      commerce as alginic sodium diester (ASD), and Zero One (Z1), a water-soluble
      agent newly reported in the CS marketplace and subsequently identified as sodium
      hexametaphosphate. ASD, Z1, and CS are similar in physical appearance and
      solubility in water and ethanol. They are also titratable anions and form ionic
      pairs with CPC, therefore interfering with the CPC titration assay for CS CAME
      separates these adulterants from each other and from CS by differences in their
      electrophoretic mobility. CAME is able to detect these impurities in CS at levels
      as low as 0.66% by weight. Although it is recommended that a method for detecting
      impurities (e.g., CAME) be used in cormbination with relatively nonspecific assay
      methods such as CPC titration, this is seldom done in practice. Assay results for
      CS derived fromn CPC titration may, therefore, be misleading, leaving the CS
      supply chain vulnerable to adulteration. In this study, the authors investigated
      ASD and Z1 adulteration of CS and developed an electrophoretic separation of
      these adulterants in CS and procedures to isolate ASD from CS matrixes containing
      these adulterants. The authors describe in this paper utilization of an
      orthogonal approach to establish the identity of Z1 as sodium hexametaphosphate
      and to confirm the identity of ASD, including ethanol fractionation, FTIR
      spectroscopy, differential scanning calorimetry, and NMR spectroscopy. The
      authors suggest that CAME is a cost-effective and easy to use methodfor detecting
      certain impurities in CS raw ingredients and recommend that CPC and CAME be used
      in combination by QC laboratories as a means of effectively deterring the
      practice of adulterating CS raw materials with the known adulterants ASD and Z1
      and/or other non-chondroitin substances that can be separated from CSby CAME and
      that exhibit CPC titration behavior similar to CS.

PMID- 25372664
TI  - Role of the Wada test and functional magnetic resonance imaging in preoperative
      mapping of language and memory: two atypical cases.
AB  - The Wada test is an invasive procedure used to determine cerebral memory and
      language dominance as well as risk of cognitive deficits following neurosurgery.
      However, the potential risks of Wada testing have led some to consider foregoing
      Wada testing in candidates for resective epilepsy surgery with right hemispheric
      seizure onset. We present two atypical cases in which the Wada test showed
      unexpected memory and language lateralization. These cases underscore the
      importance of functional magnetic resonance in which imaging and Wada examination
      in right-handed individuals even when the lesion would not suggest atypical
      language representation. 

PMID- 25372665
TI  - A non-invasive laboratory panel as a diagnostic and prognostic biomarker for
      thrombotic microangiopathy: development and application in a Chinese cohort
      study.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) in the kidney is a histopathologic
      lesion that occurs in a number of clinical settings and is often associated with
      poor renal prognosis. The standard test for the diagnosis of TMA is the renal
      biopsy; noninvasive parameters such as potential biomarkers have not been
      developed. METHODS: We analyzed routine parameters in a cohort of 220 patients
      with suspected TMA and developed a diagnostic laboratory panel by logistic
      regression. The levels of candidate markers were validated using an independent
      cohort (n = 46), a cohort of systemic lupus erythematosus (SLE) (n = 157) and an
      expanded cohort (n = 113), as well as 9 patients with repeat biopsies. RESULTS:
      Of the 220 patients in the derivation cohort, 51 patients with biopsy-proven TMA
      presented with a worse renal prognosis than those with no TMA (P = 0.002).
      Platelet and L-lactate dehydrogenase (LDH) levels showed an acceptable diagnostic
      value of TMA (AUC = 0.739 and 0.756, respectively). A panel of 4 variables -
      creatinine, platelets, ADAMTS13 (a disintegrin and metalloprotease with
      thrombospondin type 1 repeats 13) activity and LDH - can effectively discriminate
      patients with TMA (AUC = 0.800). In the validation cohort, the platelet and LDH
      levels and the 4-variable panel signature robustly distinguished patients with
      TMA. The discrimination effects of these three markers were confirmed in patients
      with SLE. Moreover, LDH levels and the 4-variable panel signature also showed
      discrimination values in an expanded set. Among patients undergoing repeat
      biopsy, increased LDH levels and panel signatures were associated with TMA status
      when paired evaluations were performed. Importantly, only the 4-variable panel
      was an independent prognostic marker for renal outcome (hazard ratio = 3.549;
      P<0.001). CONCLUSIONS: The noninvasive laboratory diagnostic panel is better for
      the early detection and prognosis of TMA compared with a single parameter, and
      may provide a promising biomarker for clinical application.

PMID- 25372666
TI  - Life without oxygen: gene regulatory responses of the crucian carp (Carassius
      carassius) heart subjected to chronic anoxia.
AB  - Crucian carp are unusual among vertebrates in surviving extended periods in the
      complete absence of molecular oxygen. During this time cardiac output is
      maintained though these mechanisms are not well understood. Using a high-density
      cDNA microarray, we have defined the genome-wide gene expression responses of
      cardiac tissue after exposing the fish at two temperatures (8 and 13  degrees C)
      to one and seven days of anoxia, followed by seven days after restoration to
      normoxia. At 8  degrees C, using a false discovery rate of 5%, neither anoxia nor
      re-oxygenation elicited appreciable changes in gene expression. By contrast, at
      13  degrees C, 777 unique genes responded strongly. Up-regulated genes included
      those involved in protein turnover, the pentose phosphate pathway and cell
      morphogenesis while down-regulated gene categories included RNA splicing and
      transcription. Most genes were affected between one and seven days of anoxia,
      indicating gene regulation over the medium term but with few early response
      genes. Re-oxygenation for 7 days was sufficient to completely reverse these
      responses. Glycolysis displayed more complex responses with anoxia up-regulated
      transcripts for the key regulatory enzymes, hexokinase and phosphofructokinase,
      but with down-regulation of most of the non-regulatory genes. This complex
      pattern of responses in genomic transcription patterns indicates divergent
      cardiac responses to anoxia, with the transcriptionally driven reprogramming of
      cardiac function seen at 13  degrees C being largely completed at 8  degrees C.

PMID- 25372667
TI  - Mechanism of inhibition of CYP1A1 and glutathione S-transferase activities in
      fish liver by quercetin, resveratrol, naringenin, hesperidin, and rutin.
AB  - Quercetin, resveratrol, naringenin, hesperidin, and rutin are phenolic
      compounds/flavonoids that may have roles in the reduction of cancer
      susceptibility. In this study, in vitro modulatory effects of them were studied
      on liver CYP1A1 associated 7-ethoxyresorufin-O-deethylase (EROD) activity and
      glutathione S-transferase (GST) activity of leaping mullet (Liza saliens). All of
      the phenolic compounds/flavonoids used exerted an inhibitory effect on both EROD
      and GST activities of fish. Quercetin, resveratrol, hesperidin, and rutin were
      found to inhibit EROD activity in a competitive manner; on the other hand,
      naringenin was found to inhibit EROD activity in a noncompetitive manner. Ki
      values of quercetin, resveratrol, naringenin, hesperidin, and rutin were
      calculated from Dixon plots as 0.12 MUM, 0.67 MUM, 2.63 MUM, 18 MUM and 0.1 mM,
      respectively. Resveratrol, quercetin, and hesperidin were found to inhibit GST
      activity in a competitive manner; on the other hand, rutin and naringenin were
      found to inhibit GST activity in a mixed-type manner. Ki values of resveratrol,
      quercetin, hesperidin, naringenin, and rutin were calculated from Dixon plots as
      3.2 MUM, 12.5 MUM, 45 MUM, 128 MUM, and 150 MUM, respectively. The results
      suggest that quercetin and resveratrol containing foods are effective in the
      prevention and treatment of cancer.

PMID- 25372668
TI  - Possible influence of B chromosomes on genes included in immune response and
      parasite burden in Apodemus flavicollis.
AB  - Genetic background underlying wild populations immune response to different
      parasites is still not well understood. We studied immune response to multiple
      infections and to competition between different parasite species at different
      developmental stages in population of yellow-necked mouse, Apodemus flavicollis.
      Quantitative real-time PCR was used to investigate associations of MHC II-DRB, IL
      10 and Tgf-beta genes expressions with presence of intestinal parasites at
      different developmental stages. Furthermore, we were interested whether the host
      related characteristics (sex, age, body condition, presence of B chromosomes or
      expression of other genes) or characteristics of present parasites (number of
      adult parasites of each identified species, egg count of each parasite genus,
      total number of nematode individuals) affect differential expression of the
      studied genes. A significant invert association between the expression of MHC II
      DRB and Tgf-beta gene was found, which together with absence of IL-10 association
      confirmed modified Th2 as the main type of immune response to nematode
      infections. Effect of recorded parasites and parasite life-cycle stage on
      expression levels of MHC II-DRB gene was detected only through interactions with
      host-related characteristics such as sex, age, and the presence of B chromosomes.
      The presence of B chromosomes is associated with lower expression level of Tgf
      beta gene. Although the influence of host genetic background on parasite
      infection has already been well documented, this is the first study in mammals
      that gave presence of B chromosomes on immune response full consideration. 

PMID- 25372669
TI  - Interfacial adsorption of peptides in oil-in-water emulsions costabilized by
      Tween 20 and antioxidative potato peptides.
AB  - Previous studies have shown that soybean oil-in-water (O/W) emulsions prepared
      with potato protein hydrolysate (PPH) are remarkably stable against oxidative
      changes. It was hypothesized that partitioning of peptides at the emulsion
      interface plays an important role in this phenomenon. The present study was
      conducted to examine the structural characteristics of the interfacial membrane.
      As revealed by atomic force microscopy, oil droplets costabilized with PPH and
      Tween 20 were more uniform than those stabilized with Tween 20 only (control).
      Confocal laser scanning microscopy images indicated the existence of peptides
      directly anchored into the interfacial membrane. The adsorbed peptides were
      mostly short oligopeptides composed of two to seven amino acids, of which Ser-Phe
      Asp-Leu(Ile)-Lys matched the sequence of patatin. The adsorption of these
      peptides appeared to both improve the integrity of the interface and contribute
      to the oxidative stability of the emulsions. Furthermore, cryogenic transmission
      electron microscopy illustrated the morphology of the interfacial membrane as a
      noncontinuous short fibril structure. Partitioning of antioxidative peptides in
      the interfacial membrane provided steric hindrances and electrostatic effects to
      inhibit oxidation. 

PMID- 25372671
TI  - Anchoring protein crystals to mounting loops with hydrogel using inkjet
      technology.
AB  - X-ray crystallography is an important technique for structure-based drug
      discovery, mainly because it is the only technique that can reveal whether a
      ligand binds to the target protein as well as where and how it binds. However,
      ligand screening by X-ray crystallography involves a crystal-soaking experiment,
      which is usually performed manually. Thus, the throughput is not satisfactory for
      screening large numbers of candidate ligands. In this study, a technique to
      anchor protein crystals to mounting loops by using gel and inkjet technology has
      been developed; the method allows soaking of the mounted crystals in ligand
      containing solution. This new technique may assist in the design of a fully
      automated drug-screening pipeline. 

PMID- 25372670
TI  - Covering complete proteomes with X-ray structures: a current snapshot.
AB  - Structural genomics programs have developed and applied structure-determination
      pipelines to a wide range of protein targets, facilitating the visualization of
      macromolecular interactions and the understanding of their molecular and
      biochemical functions. The fundamental question of whether three-dimensional
      structures of all proteins and all functional annotations can be determined using
      X-ray crystallography is investigated. A first-of-its-kind large-scale analysis
      of crystallization propensity for all proteins encoded in 1953 fully sequenced
      genomes was performed. It is shown that current X-ray crystallographic knowhow
      combined with homology modeling can provide structures for 25% of modeling
      families (protein clusters for which structural models can be obtained through
      homology modeling), with at least one structural model produced for each Gene
      Ontology functional annotation. The coverage varies between superkingdoms, with
      19% for eukaryotes, 35% for bacteria and 49% for archaea, and with those of
      viruses following the coverage values of their hosts. It is shown that the
      crystallization propensities of proteomes from the taxonomic superkingdoms are
      distinct. The use of knowledge-based target selection is shown to substantially
      increase the ability to produce X-ray structures. It is demonstrated that the
      human proteome has one of the highest attainable coverage values among
      eukaryotes, and GPCR membrane proteins suitable for X-ray structure determination
      were determined. 

PMID- 25372672
TI  - Structural basis for the recognition of muramyltripeptide by Helicobacter pylori
      Csd4, a D,L-carboxypeptidase controlling the helical cell shape.
AB  - Helicobacter pylori infection causes a variety of gastrointestinal diseases,
      including peptic ulcers and gastric cancer. Its colonization of the gastric
      mucosa of the human stomach is a prerequisite for survival in the stomach.
      Colonization depends on its motility, which is facilitated by the helical shape
      of the bacterium. In H. pylori, cross-linking relaxation or trimming of
      peptidoglycan muropeptides affects the helical cell shape. Csd4 has been
      identified as one of the cell shape-determining peptidoglycan hydrolases in H.
      pylori. It is a Zn(2+)-dependent D,L-carboxypeptidase that cleaves the bond
      between the gamma-D-Glu and the mDAP of the non-cross-linked muramyltripeptide
      (muramyl-L-Ala-gamma-D-Glu-mDAP) of the peptidoglycan to produce the
      muramyldipeptide (muramyl-L-Ala-gamma-D-Glu) and mDAP. Here, the crystal
      structure of H. pylori Csd4 (HP1075 in strain 26695) is reported in three
      different states: the ligand-unbound form, the substrate-bound form and the
      product-bound form. H. pylori Csd4 consists of three domains: an N-terminal D,L
      carboxypeptidase domain with a typical carboxypeptidase fold, a central beta
      barrel domain with a novel fold and a C-terminal immunoglobulin-like domain. The
      D,L-carboxypeptidase domain recognizes the substrate by interacting primarily
      with the terminal mDAP moiety of the muramyltripeptide. It undergoes a
      significant structural change upon binding either mDAP or the mDAP-containing
      muramyltripeptide. It it also shown that Csd5, another cell-shape determinant in
      H. pylori, is capable of interacting not only with H. pylori Csd4 but also with
      the dipeptide product of the reaction catalyzed by Csd4. 

PMID- 25372674
TI  - Insights into the relationship between the haem-binding pocket and the redox
      potential of c6 cytochromes: four atomic resolution structures of c6 and c6-like
      proteins from Synechococcus sp. PCC 7002.
AB  - The structure of cytochrome c6C from the mesophilic cyanobacterium Synechococcus
      sp. PCC 7002 has been determined at 1.03 A resolution. This is the first
      structural report on the recently discovered cyanobacterial cytochrome c6-like
      proteins found in marine and nitrogen-fixing cyanobacteria. Despite high
      similarity in the overall three-dimensional fold between cytochromes c6 and c6C,
      the latter shows saliently different electrostatic properties in terms of surface
      charge distribution and dipole moments. Its midpoint redox potential is less than
      half of the value for typical c6 cytochromes and results mainly from the
      substitution of one residue in the haem pocket. Here, high-resolution crystal
      structures of mutants of both cytochromes c6 and c6C are presented, and the
      impact of the mutation of specific residues in the haem-binding pocket on the
      redox potential is discussed. These findings contribute to the elucidation of the
      structure-function relationship of c6-like cytochromes. 

PMID- 25372673
TI  - Anthrax toxin lethal factor domain 3 is highly mobile and responsive to ligand
      binding.
AB  - The secreted anthrax toxin consists of three components: the protective antigen
      (PA), edema factor (EF) and lethal factor (LF). LF, a zinc metalloproteinase,
      compromises the host immune system primarily by targeting mitogen-activated
      protein kinase kinases in macrophages. Peptide substrates and small-molecule
      inhibitors bind LF in the space between domains 3 and 4 of the hydrolase. Domain
      3 is attached on a hinge to domain 2 via residues Ile300 and Pro385, and can move
      through an angular arc of greater than 35 degrees  in response to the binding of
      different ligands. Here, multiple LF structures including five new complexes with
      co-crystallized inhibitors are compared and three frequently populated LF
      conformational states termed 'bioactive', 'open' and 'tight' are identified. The
      bioactive position is observed with large substrate peptides and leaves all
      peptide-recognition subsites open and accessible. The tight state is seen in
      unliganded and small-molecule complex structures. In this state, domain 3 is
      clamped over certain substrate subsites, blocking access. The open position
      appears to be an intermediate state between these extremes and is observed owing
      to steric constraints imposed by specific bound ligands. The tight conformation
      may be the lowest-energy conformation among the reported structures, as it is the
      position observed with no bound ligand, while the open and bioactive
      conformations are likely to be ligand-induced. 

PMID- 25372675
TI  - Structures of K42N and K42Y sperm whale myoglobins point to an inhibitory role of
      distal water in peroxidase activity.
AB  - Sperm whale myoglobin (Mb) functions as an oxygen-storage protein, but in the
      ferric state it possesses a weak peroxidase activity which enables it to carry
      out H2O2-dependent dehalogenation reactions. Hemoglobin/dehaloperoxidase from
      Amphitrite ornata (DHP) is a dual-function protein represented by two isoproteins
      DHP A and DHP B; its peroxidase activity is at least ten times stronger than that
      of Mb and plays a physiological role. The 'DHP A-like' K42Y Mb mutant (K42Y) and
      the 'DHP B-like' K42N mutant (K42N) were engineered in sperm whale Mb to mimic
      the extended heme environments of DHP A and DHP B, respectively. The peroxidase
      reaction rates increased ~3.5-fold and ~5.5-fold in K42Y and K42N versus Mb,
      respectively. The crystal structures of the K42Y and K42N mutants revealed that
      the substitutions at position 42 slightly elongate not only the distances between
      the distal His55 and the heme iron but also the hydrogen-bonding distances
      between His55 and the Fe-coordinated water. The enhanced peroxidase activity of
      K42Y and K42N thus might be attributed in part to the weaker binding of the axial
      water molecule that competes with hydrogen peroxide for the binding site at the
      heme in the ferric state. This is likely to be the mechanism by which the
      relationship 'longer distal histidine to Fe distance - better peroxidase
      activity', which was previously proposed for heme proteins by Matsui et al.
      (1999) (J. Biol. Chem. 274, 2838-2844), works. Furthermore, positive
      cooperativity in K42N was observed when its dehaloperoxidase activity was
      measured as a function of the concentration of the substrate trichlorophenol.
      This serendipitously engineered cooperativity was rationalized by K42N
      dimerization through the formation of a dityrosine bond induced by excess H2O2. 

PMID- 25372676
TI  - The structural basis of urea-induced protein unfolding in beta-catenin.
AB  - Although urea and guanidine hydrochloride are commonly used to denature proteins,
      the molecular underpinnings of this process have remained unclear for a century.
      To address this question, crystal structures of beta-catenin were determined at
      various urea concentrations. These structures contained at least 105 unique
      positions that were occupied by urea molecules, each of which interacted with the
      protein primarily via hydrogen bonds. Hydrogen-bond competition experiments
      showed that the denaturing effects of urea were neutralized when polyethylene
      glycol was added to the solution. These data suggest that urea primarily causes
      proteins to unfold by competing and disrupting hydrogen bonds in proteins.
      Moreover, circular-dichroism spectra and nuclear magnetic resonance (NMR)
      analysis revealed that a similar mechanism caused protein denaturation in the
      absence of urea at pH levels greater than 12. Taken together, the results led to
      the conclusion that the disruption of hydrogen bonds is a general mechanism of
      unfolding induced by urea, high pH and potentially other denaturing agents such
      as guanidine hydrochloride. Traditionally, the disruption of hydrophobic
      interactions instead of hydrogen bonds has been thought to be the most important
      cause of protein denaturation. 

PMID- 25372677
TI  - Structure, mechanism and ensemble formation of the alkylhydroperoxide reductase
      subunits AhpC and AhpF from Escherichia coli.
AB  - Hydroperoxides are reactive oxygen species (ROS) that are toxic to all cells and
      must be converted into the corresponding alcohols to alleviate oxidative stress.
      In Escherichia coli, the enzyme primarily responsible for this reaction is
      alkylhydroperoxide reductase (AhpR). Here, the crystal structures of both of the
      subunits of EcAhpR, EcAhpF (57 kDa) and EcAhpC (21 kDa), have been solved. The
      EcAhpF structures (2.0 and 2.65 A resolution) reveal an open and elongated
      conformation, while that of EcAhpC (3.3 A resolution) forms a decameric ring.
      Solution X-ray scattering analysis of EcAhpF unravels the flexibility of its N
      terminal domain, and its binding to EcAhpC was demonstrated by isothermal
      titration calorimetry. These studies suggest a novel overall mechanistic model of
      AhpR as a hydroperoxide scavenger, in which the dimeric, extended AhpF prefers
      complex formation with the AhpC ring to accelerate the catalytic activity and
      thus to increase the chance of rescuing the cell from ROS. 

PMID- 25372678
TI  - Structure of mouse muskelin discoidin domain and biochemical characterization of
      its self-association.
AB  - Muskelin is an intracellular kelch-repeat protein comprised of discoidin, LisH,
      CTLH and kelch-repeat domains. It is involved in cell adhesion and the regulation
      of cytoskeleton dynamics as well as being a component of a putative E3 ligase
      complex. Here, the first crystal structure of mouse muskelin discoidin domain (MK
      DD) is reported at 1.55 A resolution, which reveals a distorted eight-stranded
      beta-barrel with two short alpha-helices at one end of the barrel. Interestingly,
      the N- and C-termini are not linked by the disulfide bonds found in other
      eukaryotic discoidin structures. A highly conserved MIND motif appears to be the
      determinant for MK-DD specific interaction together with the spike loops.
      Analysis of interdomain interaction shows that MK-DD binds the kelch-repeat
      domain directly and that this interaction depends on the presence of the LisH
      domain. 

PMID- 25372679
TI  - Enzyme-substrate complex structures of CYP154C5 shed light on its mode of highly
      selective steroid hydroxylation.
AB  - CYP154C5 from Nocardia farcinica is a bacterial cytochrome P450 monooxygenase
      active on steroid molecules. The enzyme has recently been shown to exhibit
      exclusive regioselectivity and stereoselectivity in the conversion of various
      pregnans and androstans, yielding 16alpha-hydroxylated steroid products. This
      makes the enzyme an attractive candidate for industrial application in steroid
      hormone synthesis. Here, crystal structures of CYP154C5 in complex with four
      different steroid molecules were solved at resolutions of up to 1.9 A. These are
      the first reported P450 structures from the CYP154 family in complex with a
      substrate. The active site of CYP154C5 forms a flattened hydrophobic channel with
      two opposing polar regions, perfectly resembling the size and polarity
      distribution of the steroids and thus resulting in highly specific steroid
      binding with Kd values in the range 10-100 nM. Key enzyme-substrate interactions
      were identified that accounted for the exclusive regioselectivity and
      stereoselectivity of the enzyme. Additionally, comparison of the four CYP154C5
      steroid structures revealed distinct structural differences, explaining the
      observed variations in kinetic data obtained for this P450 with the steroids
      pregnenolone, dehydroepiandrosterone, progesterone, androstenedione, testosterone
      and nandrolone. This will facilitate the generation of variants with improved
      activity or altered selectivity in the future by means of protein engineering. 

PMID- 25372680
TI  - Temperature-dependent radiation sensitivity and order of 70S ribosome crystals.
AB  - All evidence to date indicates that at T = 100 K all protein crystals exhibit
      comparable sensitivity to X-ray damage when quantified using global metrics such
      as change in scaling B factor or integrated intensity versus dose. This is
      consistent with observations in cryo-electron microscopy, and results because
      nearly all diffusive motions of protein and solvent, including motions induced by
      radiation damage, are frozen out. But how do the sensitivities of different
      proteins compare at room temperature, where radiation-induced radicals are free
      to diffuse and protein and lattice structures are free to relax in response to
      local damage? It might be expected that a large complex with extensive
      conformational degrees of freedom would be more radiation sensitive than a small,
      compact globular protein. As a test case, the radiation sensitivity of 70S
      ribosome crystals has been examined. At T = 100 and 300 K, the half doses are 64
      MGy (at 3 A resolution) and 150 kGy (at 5 A resolution), respectively. The
      maximum tolerable dose in a crystallography experiment depends upon the initial
      or desired resolution. When differences in initial data-set resolution are
      accounted for, the former half dose is roughly consistent with that for model
      proteins, and the 100/300 K half-dose ratio is roughly a factor of ten larger.
      70S ribosome crystals exhibit substantially increased resolution at 100 K
      relative to 300 K owing to cooling-induced ordering and not to reduced radiation
      sensitivity and slower radiation damage. 

PMID- 25372682
TI  - Effect of the L499M mutation of the ascomycetous Botrytis aclada laccase on redox
      potential and catalytic properties.
AB  - Laccases are members of a large family of multicopper oxidases that catalyze the
      oxidation of a wide range of organic and inorganic substrates accompanied by the
      reduction of dioxygen to water. These enzymes contain four Cu atoms per molecule
      organized into three sites: T1, T2 and T3. In all laccases, the T1 copper ion is
      coordinated by two histidines and one cysteine in the equatorial plane and is
      covered by the side chains of hydrophobic residues in the axial positions. The
      redox potential of the T1 copper ion influences the enzymatic reaction and is
      determined by the nature of the axial ligands and the structure of the second
      coordination sphere. In this work, the laccase from the ascomycete Botrytis
      aclada was studied, which contains conserved Ile491 and nonconserved Leu499
      residues in the axial positions. The three-dimensional structures of the wild
      type enzyme and the L499M mutant were determined by X-ray crystallography at 1.7
      A resolution. Crystals suitable for X-ray analysis could only be grown after
      deglycosylation. Both structures did not contain the T2 copper ion. The catalytic
      properties of the enzyme were characterized and the redox potentials of both
      enzyme forms were determined: E0 = 720 and 580 mV for the wild-type enzyme and
      the mutant, respectively. Since the structures of the wild-type and mutant forms
      are very similar, the change in the redox potential can be related to the L499M
      mutation in the T1 site of the enzyme. 

PMID- 25372683
TI  - Structure of ADC-68, a novel carbapenem-hydrolyzing class C extended-spectrum
      beta-lactamase isolated from Acinetobacter baumannii.
AB  - Outbreaks of multidrug-resistant bacterial infections have become more frequent
      worldwide owing to the emergence of several different classes of beta-lactamases.
      In this study, the molecular, biochemical and structural characteristics of an
      Acinetobacter-derived cephalosporinase (ADC)-type class C beta-lactamase, ADC-68,
      isolated from the carbapenem-resistant A. baumannii D015 were investigated. The
      blaADC-68 gene which encodes ADC-68 was confirmed to exist on the chromosome via
      Southern blot analysis and draft genome sequencing. The catalytic kinetics of
      beta-lactams and their MICs (minimum inhibitory concentrations) for A. baumannii
      D015 and purified ADC-68 (a carbapenemase obtained from this strain) were
      assessed: the strain was resistant to penicillins, narrow-spectrum and extended
      spectrum cephalosporins, and carbapenems, which were hydrolyzed by ADC-68. The
      crystal structure of ADC-68 was determined at a resolution of 1.8 A. The
      structure of ADC-68 was compared with that of ADC-1 (a non-carbapenemase);
      differences were found in the central part of the Omega-loop and the C-loop
      constituting the edge of the R1 and R2 subsites and are close to the catalytic
      serine residue Ser66. The ADC-68 C-loop was stabilized in the open conformation
      of the upper R2 subsite and could better accommodate carbapenems with larger R2
      side chains. Furthermore, a wide-open conformation of the R2-loop allowed ADC-68
      to bind to and hydrolyze extended-spectrum cephalosporins. Therefore, ADC-68 had
      enhanced catalytic efficiency against these clinically important beta-lactams
      (extended-spectrum cephalosporins and carbapenems). ADC-68 is the first reported
      enzyme among the chromosomal class C beta-lactamases to possess class C extended
      spectrum beta-lactamase and carbapenemase activities. 

PMID- 25372681
TI  - Structural insights into the human RyR2 N-terminal region involved in cardiac
      arrhythmias.
AB  - Human ryanodine receptor 2 (hRyR2) mediates calcium release from the sarcoplasmic
      reticulum, enabling cardiomyocyte contraction. The N-terminal region of hRyR2
      (amino acids 1-606) is the target of >30 arrhythmogenic mutations and contains a
      binding site for phosphoprotein phosphatase 1. Here, the solution and crystal
      structures determined under near-physiological conditions, as well as a homology
      model of the hRyR2 N-terminal region, are presented. The N-terminus is held
      together by a unique network of interactions among its three domains, A, B and C,
      in which the central helix (amino acids 410-437) plays a prominent stabilizing
      role. Importantly, the anion-binding site reported for the mouse RyR2 N-terminal
      region is notably absent from the human RyR2. The structure concurs with the
      differential stability of arrhythmogenic mutations in the central helix (R420W,
      I419F and I419F/R420W) which are owing to disparities in the propensity of
      mutated residues to form energetically favourable or unfavourable contacts. In
      solution, the N-terminus adopts a globular shape with a prominent tail that is
      likely to involve residues 545-606, which are unresolved in the crystal
      structure. Docking the N-terminal domains into cryo-electron microscopy maps of
      the closed and open RyR1 conformations reveals C(alpha) atom movements of up to 8
      A upon channel gating, and predicts the location of the leucine-isoleucine zipper
      segment and the interaction site for spinophilin and phosphoprotein phosphatase 1
      on the RyR surface. 

PMID- 25372684
TI  - Structural characterization of the virulence factor nuclease A from Streptococcus
      agalactiae.
AB  - The group B pathogen Streptococcus agalactiae commonly populates the human gut
      and urogenital tract, and is a major cause of infection-based mortality in
      neonatal infants and in elderly or immunocompromised adults. Nuclease A
      (GBS_NucA), a secreted DNA/RNA nuclease, serves as a virulence factor for S.
      agalactiae, facilitating bacterial evasion of the human innate immune response.
      GBS_NucA efficiently degrades the DNA matrix component of neutrophil
      extracellular traps (NETs), which attempt to kill and clear invading bacteria
      during the early stages of infection. In order to better understand the
      mechanisms of DNA substrate binding and catalysis of GBS_NucA, the high
      resolution structure of a catalytically inactive mutant (H148G) was solved by X
      ray crystallography. Several mutants on the surface of GBS_NucA which might
      influence DNA substrate binding and catalysis were generated and evaluated using
      an imidazole chemical rescue technique. While several of these mutants severely
      inhibited nuclease activity, two mutants (K146R and Q183A) exhibited
      significantly increased activity. These structural and biochemical studies have
      greatly increased our understanding of the mechanism of action of GBS_NucA in
      bacterial virulence and may serve as a foundation for the structure-based drug
      design of antibacterial compounds targeted to S. agalactiae. 

PMID- 25372686
TI  - Ligand-dependent active-site closure revealed in the crystal structure of
      Mycobacterium tuberculosis MenB complexed with product analogues.
AB  - 1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase catalyzes an essential
      intramolecular Claisen condensation in menaquinone biosynthesis and is an
      important target for the development of new antibiotics. This enzyme in
      Mycobacterium tuberculosis is cofactor-free and is classified as a type II DHNA
      CoA synthase, differing from type I enzymes, which rely on exogenous bicarbonate
      for catalysis. Its crystal structures in complex with product analogues have been
      determined at high resolution to reveal ligand-dependent structural changes,
      which include the ordering of a 27-residue active-site loop (amino acids 107-133)
      and the reorientation of the carboxy-terminal helix (amino acids 289-301) that
      forms part of the active site from the opposing subunit across the trimer-trimer
      interface. These structural changes result in closure of the active site to the
      bulk solution, which is likely to take place through an induced-fit mechanism,
      similar to that observed for type I DHNA-CoA synthases. These findings
      demonstrate that the ligand-dependent conformational changes are a conserved
      feature of all DHNA-CoA synthases, providing new insights into the catalytic
      mechanism of this essential tubercular enzyme. 

PMID- 25372685
TI  - A novel member of glycoside hydrolase family 30 subfamily 8 with altered
      substrate specificity.
AB  - Endoxylanases classified into glycoside hydrolase family 30 subfamily 8 (GH30-8)
      are known to hydrolyze the hemicellulosic polysaccharide glucuronoxylan (GX) but
      not arabinoxylan or neutral xylooligosaccharides. This is owing to the
      specificity of these enzymes for the alpha-1,2-linked glucuronate (GA) appendage
      of GX. Limit hydrolysis of this substrate produces a series of aldouronates each
      containing a single GA substituted on the xylose penultimate to the reducing
      terminus. In this work, the structural and biochemical characterization of
      xylanase 30A from Clostridium papyrosolvens (CpXyn30A) is presented. This
      xylanase possesses a high degree of amino-acid identity to the canonical GH30-8
      enzymes, but lacks the hallmark beta8-alpha8 loop region which in part defines
      the function of this GH30 subfamily and its role in GA recognition. CpXyn30A is
      shown to have a similarly low activity on all xylan substrates, while hydrolysis
      of xylohexaose revealed a competing transglycosylation reaction. These findings
      are directly compared with the model GH30-8 enzyme from Bacillus subtilis, XynC.
      Despite its high sequence identity to the GH30-8 enzymes, CpXyn30A does not have
      any apparent specificity for the GA appendage. These findings confirm that the
      typically conserved beta8-alpha8 loop region of these enzymes influences xylan
      substrate specificity but not necessarily beta-1,4-xylanase function. 

PMID- 25372687
TI  - Structural insights into the substrate specificity and transglycosylation
      activity of a fungal glycoside hydrolase family 5 beta-mannosidase.
AB  - beta-Mannosidases are exo-acting glycoside hydrolases (GHs) that catalyse the
      removal of the nonreducing end beta-D-mannose from manno-oligosaccharides or
      mannoside-substituted molecules. They play important roles in fundamental
      biological processes and also have potential applications in various industries.
      In this study, the first fungal GH family 5 beta-mannosidase (RmMan5B) from
      Rhizomucor miehei was functionally and structurally characterized. RmMan5B
      exhibited a much higher activity against manno-oligosaccharides than against p
      nitrophenyl beta-D-mannopyranoside (pNPM) and had a transglycosylation activity
      which transferred mannosyl residues to sugars such as fructose. To investigate
      its substrate specificity and transglycosylation activity, crystal structures of
      RmMan5B and of its inactive E202A mutant in complex with mannobiose, mannotriose
      and mannosyl-fructose were determined at resolutions of 1.3, 2.6, 2.0 and 2.4 A,
      respectively. In addition, the crystal structure of R. miehei beta-mannanase
      (RmMan5A) was determined at a resolution of 2.3 A. Both RmMan5A and RmMan5B adopt
      the (beta/alpha)8-barrel architecture, which is globally similar to the other
      members of GH family 5. However, RmMan5B shows several differences in the loop
      around the active site. The extended loop between strand beta8 and helix alpha8
      (residues 354-392) forms a 'double' steric barrier to 'block' the substrate
      binding cleft at the end of the -1 subsite. Trp119, Asn260 and Glu380 in the beta
      mannosidase, which are involved in hydrogen-bond contacts with the -1 mannose,
      might be essential for exo catalytic activity. Moreover, the structure of RmMan5B
      in complex with mannosyl-fructose has provided evidence for the interactions
      between the beta-mannosidase and D-fructofuranose. Overall, the present study not
      only helps in understanding the catalytic mechanism of GH family 5 beta
      mannosidases, but also provides a basis for further enzymatic engineering of beta
      mannosidases and beta-mannanases. 

PMID- 25372688
TI  - Small-angle neutron scattering reveals the assembly mode and oligomeric
      architecture of TET, a large, dodecameric aminopeptidase.
AB  - The specific self-association of proteins into oligomeric complexes is a common
      phenomenon in biological systems to optimize and regulate their function.
      However, de novo structure determination of these important complexes is often
      very challenging for atomic-resolution techniques. Furthermore, in the case of
      homo-oligomeric complexes, or complexes with very similar building blocks, the
      respective positions of subunits and their assembly pathways are difficult to
      determine using many structural biology techniques. Here, an elegant and powerful
      approach based on small-angle neutron scattering is applied, in combination with
      deuterium labelling and contrast variation, to elucidate the oligomeric
      organization of the quaternary structure and the assembly pathways of 468 kDa,
      hetero-oligomeric and symmetric Pyrococcus horikoshii TET2-TET3 aminopeptidase
      complexes. The results reveal that the topology of the PhTET2 and PhTET3 dimeric
      building blocks within the complexes is not casual but rather suggests that their
      quaternary arrangement optimizes the catalytic efficiency towards peptide
      substrates. This approach bears important potential for the determination of
      quaternary structures and assembly pathways of large oligomeric and symmetric
      complexes in biological systems. 

PMID- 25372689
TI  - Structure-specificity relationships in Abp, a GH27 beta-L-arabinopyranosidase
      from Geobacillus stearothermophilus T6.
AB  - L-Arabinose sugar residues are relatively abundant in plants and are found mainly
      in arabinan polysaccharides and in other arabinose-containing polysaccharides
      such as arabinoxylans and pectic arabinogalactans. The majority of the arabinose
      units in plants are present in the furanose form and only a small fraction of
      them are present in the pyranose form. The L-arabinan-utilization system in
      Geobacillus stearothermophilus T6, a Gram-positive thermophilic soil bacterium,
      has recently been characterized, and one of the key enzymes was found to be an
      intracellular beta-L-arabinopyranosidase (Abp). Abp, a GH27 enzyme, was shown to
      remove beta-L-arabinopyranose residues from synthetic substrates and from the
      native substrates sugar beet arabinan and larch arabinogalactan. The Abp monomer
      is made up of 448 amino acids, and based on sequence homology it was suggested
      that Asp197 is the catalytic nucleophile and Asp255 is the catalytic acid/base.
      In the current study, the detailed three-dimensional structure of wild-type Abp
      (at 2.28 A resolution) and its catalytic mutant Abp-D197A with (at 2.20 A
      resolution) and without (at 2.30 A resolution) a bound L-arabinose product are
      reported as determined by X-ray crystallography. These structures demonstrate
      that the three-dimensional structure of the Abp monomer correlates with the
      general fold observed for GH27 proteins, consisting of two main domains: an N
      terminal TIM-barrel domain and a C-terminal all-beta domain. The two catalytic
      residues are located in the TIM-barrel domain, such that their carboxylic
      functional groups are about 5.9 A from each other, consistent with a retaining
      mechanism. An isoleucine residue (Ile67) located at a key position in the active
      site is shown to play a critical role in the substrate specificity of Abp,
      providing a structural basis for the high preference of the enzyme towards
      arabinopyranoside over galactopyranoside substrates. The crystal structure
      demonstrates that Abp is a tetramer made up of two 'open-pincers' dimers, which
      clamp around each other to form a central cavity. The four active sites of the
      Abp tetramer are situated on the inner surface of this cavity, all opening into
      the central space of the cavity. The biological relevance of this tetrameric
      structure is supported by independent results obtained from size-exclusion
      chromatography (SEC), dynamic light-scattering (DLS) and small-angle X-ray
      scattering (SAXS) experiments. These data and their comparison to the structural
      data of related GH27 enzymes are used for a more general discussion concerning
      structure-selectivity aspects in this glycoside hydrolase (GH) family. 

PMID- 25372690
TI  - Structure of the gas vesicle protein GvpF from the cyanobacterium Microcystis
      aeruginosa.
AB  - Gas vesicles are gas-filled proteinaceous organelles that provide buoyancy for
      bacteria and archaea. A gene cluster that is highly conserved in various species
      encodes about 8-14 proteins (Gvp proteins) that are involved in the formation of
      gas vesicles. Here, the first crystal structure of the gas vesicle protein GvpF
      from Microcystis aeruginosa PCC 7806 is reported at 2.7 A resolution. GvpF is
      composed of two structurally distinct domains (the N-domain and C-domain), both
      of which display an alpha+beta class overall structure. The N-domain adopts a
      novel fold, whereas the C-domain has a modified ferredoxin fold with an apparent
      variation owing to an extension region consisting of three sequential helices.
      The two domains pack against each other via interactions with a C-terminal tail
      that is conserved among cyanobacteria. Taken together, it is concluded that the
      overall architecture of GvpF presents a novel fold. Moreover, it is shown that
      GvpF is most likely to be a structural protein that is localized at the gas
      facing surface of the gas vesicle by immunoblotting and immunogold labelling
      based tomography. 

PMID- 25372691
TI  - Structure-based identification of inositol polyphosphate 1-phosphatase from
      Entamoeba histolytica.
AB  - Inositol polyphosphate 1-phosphatase from Entamoeba histolytica (EhIPPase) is an
      Mg(2+)-dependent and Li(+)-sensitive enzyme that catalyzes the hydrolysis of
      inositol 1,4-bisphosphate [Ins(1,4)P2] into myo-inositol 1-monophosphate and
      PO4(3-). In the present work, EhIPPase has been biochemically identified and its
      crystal structure has been determined in the presence of Mg(2+) and PO4(3-) at
      2.5 A resolution. This enzyme was previously classified as a 3'(2'),5'
      bisphosphate nucleotidase in the NCBI, but its biochemical activity and
      structural analysis suggest that this enzyme behaves more like an inositol
      polyphosphate 1-phosphatase. The ability of EhIPPase to hydrolyze the smaller
      Ins(1,4)P2 better than the bulkier 3'-phosphoadenosine 5'-phosphate (PAP) is
      explained on the basis of the orientations of amino-acid residues in the binding
      site. This structure is the first of its class to be determined from any
      protozoan parasite, and is the third to determined among all organisms, following
      its rat and bovine homologues. The three-dimensional fold of EhIPPase is similar
      to those of other members of the inositol monophosphatase superfamily, which also
      includes inositol monophosphatase, 3'(2'),5'-bisphosphate nucleotidase and
      fructose-1,6-bisphosphate 1-phosphatase. They all share conserved residues
      essential for metal binding and substrate hydrolysis, with the motif D-Xn-EE-Xn
      DP(I/L)DG(S/T)-Xn-WD-Xn-GG. The structure is divided into two domains, namely
      alpha+beta and alpha/beta, and the substrate and metal ions bind between them.
      However, the ability of each enzyme class to act specifically on its cognate
      substrate is governed by the class-specific amino-acid residues at the active
      site. 

PMID- 25372692
TI  - Alliin is a suicide substrate of Citrobacter freundii methionine gamma-lyase:
      structural bases of inactivation of the enzyme.
AB  - The interaction of Citrobacter freundii methionine gamma-lyase (MGL) and the
      mutant form in which Cys115 is replaced by Ala (MGL C115A) with the nonprotein
      amino acid (2R)-2-amino-3-[(S)-prop-2-enylsulfinyl]propanoic acid (alliin) was
      investigated. It was found that MGL catalyzes the beta-elimination reaction of
      alliin to form 2-propenethiosulfinate (allicin), pyruvate and ammonia. The beta
      elimination reaction of alliin is followed by the inactivation and modification
      of SH groups of the wild-type and mutant enzymes. Three-dimensional structures of
      inactivated wild-type MGL (iMGL wild type) and a C115A mutant form (iMGL C115A)
      were determined at 1.85 and 1.45 A resolution and allowed the identification of
      the SH groups that were oxidized by allicin. On this basis, the mechanism of the
      inactivation of MGL by alliin, a new suicide substrate of MGL, is proposed. 

PMID- 25372693
TI  - Enzyme-adenylate structure of a bacterial ATP-dependent DNA ligase with a
      minimized DNA-binding surface.
AB  - DNA ligases are a structurally diverse class of enzymes which share a common
      catalytic core and seal breaks in the phosphodiester backbone of double-stranded
      DNA via an adenylated intermediate. Here, the structure and activity of a
      recombinantly produced ATP-dependent DNA ligase from the bacterium Psychromonas
      sp. strain SP041 is described. This minimal-type ligase, like its close
      homologues, is able to ligate singly nicked double-stranded DNA with high
      efficiency and to join cohesive-ended and blunt-ended substrates to a more
      limited extent. The 1.65 A resolution crystal structure of the enzyme-adenylate
      complex reveals no unstructured loops or segments, and suggests that this enzyme
      binds the DNA without requiring full encirclement of the DNA duplex. This is in
      contrast to previously characterized minimal DNA ligases from viruses, which use
      flexible loop regions for DNA interaction. The Psychromonas sp. enzyme is the
      first structure available for the minimal type of bacterial DNA ligases and is
      the smallest DNA ligase to be crystallized to date. 

PMID- 25372694
TI  - Elucidation of the bicarbonate binding site and insights into the carboxylation
      mechanism of (N(5))-carboxyaminoimidazole ribonucleotide synthase (PurK) from
      Bacillus anthracis.
AB  - Structures of (N(5))-carboxyaminoimidazole ribonucleotide synthase (PurK) from
      Bacillus anthracis with various combinations of ATP, ADP, Mg(2+), bicarbonate and
      aminoimidazole ribonucleotide (AIR) in the active site are presented. The binding
      site of bicarbonate has only been speculated upon previously, but is shown here
      for the first time. The binding involves interactions with the conserved residues
      Arg272, His274 and Lys348. These structures provide insights into each ligand in
      the active site and allow a possible mechanism to be proposed for the reaction
      that converts bicarbonate and AIR, in the presence of ATP, to produce (N(5))
      carboxyaminoimidazole ribonucleotide. The formation of a carboxyphosphate
      intermediate through ATP phosphoryl transfer is proposed, followed by
      carboxylation of AIR to give the product, facilitated by a cluster of conserved
      residues and an active-site water network. 

PMID- 25372695
TI  - Structural and functional characterization of an arylamine N-acetyltransferase
      from the pathogen Mycobacterium abscessus: differences from other mycobacterial
      isoforms and implications for selective inhibition.
AB  - Mycobacterium abscessus is the most pathogenic rapid-growing mycobacterium and is
      one of the most resistant organisms to chemotherapeutic agents. However,
      structural and functional studies of M. abscessus proteins that could
      modify/inactivate antibiotics remain nonexistent. Here, the structural and
      functional characterization of an arylamine N-acetyltransferase (NAT) from M.
      abscessus [(MYCAB)NAT1] are reported. This novel prokaryotic NAT displays
      significant N-acetyltransferase activity towards aromatic substrates, including
      antibiotics such as isoniazid and p-aminosalicylate. The enzyme is endogenously
      expressed and functional in both the rough and smooth M. abscessus morphotypes.
      The crystal structure of (MYCAB)NAT1 at 1.8 A resolution reveals that it is more
      closely related to Nocardia farcinica NAT than to mycobacterial isoforms. In
      particular, structural and physicochemical differences from other mycobacterial
      NATs were found in the active site. Peculiarities of (MYCAB)NAT1 were further
      supported by kinetic and docking studies showing that the enzyme was poorly
      inhibited by the piperidinol inhibitor of mycobacterial NATs. This study
      describes the first structure of an antibiotic-modifying enzyme from M. abscessus
      and provides bases to better understand the substrate/inhibitor-binding
      specificities among mycobacterial NATs and to identify/optimize specific
      inhibitors. These data should also contribute to the understanding of the
      mechanisms that are responsible for the pathogenicity and extensive
      chemotherapeutic resistance of M. abscessus. 

PMID- 25372698
TI  - New Directions and Developments in Managed Care Financing.
AB  - This overview discusses articles published in this issue of the Health Care
      Financing Review, entitled "Managed Care: Advances in Financing." Articles cover
      the cutting-edge developments in payment methods for managed care organizations
      and their providers; new approaches to financing managed health care services for
      Medicare and Medicaid beneficiaries and special sub-populations; and the
      financing challenges presented by new managed care delivery models and industry
      consolidation.

PMID- 25372696
TI  - Structure of the OsSERK2 leucine-rich repeat extracellular domain.
AB  - Somatic embryogenesis receptor kinases (SERKs) are leucine-rich repeat (LRR)
      containing integral membrane receptors that are involved in the regulation of
      development and immune responses in plants. It has recently been shown that rice
      SERK2 (OsSERK2) is essential for XA21-mediated resistance to the pathogen
      Xanthomonas oryzae pv. oryzae. OsSERK2 is also required for the BRI1-mediated,
      FLS2-mediated and EFR-mediated responses to brassinosteroids, flagellin and
      elongation factor Tu (EF-Tu), respectively. Here, crystal structures of the LRR
      domains of OsSERK2 and a D128N OsSERK2 mutant, expressed as hagfish variable
      lymphocyte receptor (VLR) fusions, are reported. These structures suggest that
      the aspartate mutation does not generate any significant conformational change in
      the protein, but instead leads to an altered interaction with partner receptors. 

PMID- 25372699
TI  - In vivo characterization of neutrophil extracellular traps in various organs of a
      murine sepsis model.
AB  - Neutrophil extracellular traps (NETs) represent extracellular microbial trapping
      and killing. Recently, it has been implicated in thrombogenesis, autoimmune
      disease, and cancer progression. The aim of this study was to characterize NETs
      in various organs of a murine sepsis model in vivo and to investigate their
      associations with platelets, leukocytes, or vascular endothelium. NETs were
      classified as two distinct forms; cell-free NETs that were released away from
      neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell
      free NETs were characterized as fragmented or cotton-like structures, while
      anchored NETs were characterized as linear, reticular, membranous, or spot-like
      structures. In septic mice, both anchored and cell-free NETs were significantly
      increased in postcapillary venules of the cecum and hepatic sinusoids with
      increased leukocyte-endothelial interactions. NETs were also observed in both
      alveolar space and pulmonary capillaries of the lung. The interactions of NETs
      with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium
      of arterioles and venules were observed in the microcirculation of septic mice.
      Microvessel occlusions which may be caused by platelet aggregates or leukocyte
      platelet aggregates and heterogeneously decreased blood flow were also observed
      in septic mice. NETs appeared to be associated with the formation of platelet
      aggregates or leukocyte-platelet aggregates. These observational findings may
      suggest the adverse effect of intravascular NETs on the host during a sepsis. 

PMID- 25372700
TI  - Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth: a
      systematic review.
AB  - BACKGROUND: Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is
      ubiquitous in most regions of the world. The most commonly studied PFASs are
      perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies
      indicate that maternal PFAS exposure is associated with reduced fetal growth.
      However, the results of human studies are inconsistent. OBJECTIVES: To summarize
      the evidence of an association between exposure to PFASs, particularly PFOS and
      PFOA, and human fetal growth. METHODS: Systematic literature searches were
      performed in MEDLINE and EMBASE. We included original studies on pregnant women
      with measurements of PFOA or PFOS in maternal blood during pregnancy or the
      umbilical cord and associations with birth weight or related outcomes according
      to the PFAS level. Citations and references from the included articles were
      investigated to locate more relevant articles. Study characteristics and results
      were extracted to structured tables. The completeness of reporting as well as the
      risk of bias and confounding were assessed. RESULTS: Fourteen studies were
      eligible. In utero PFOA exposure was associated with decreased measures of
      continuous birth weight in all studies, even though the magnitude of the
      association differed and many results were statistically insignificant. PFOS
      exposure and birth weight were associated in some studies, while others found no
      association. CONCLUSIONS: Higher PFOS and PFOA concentrations were associated
      with decreased average birth weight in most studies, but only some results were
      statistically significant. The impact on public health is unclear, but the global
      exposure to PFASs warrants further investigation.

PMID- 25372701
TI  - Developmental immunotoxicity of chemicals in rodents and its possible regulatory
      impact.
AB  - Around 25% of the children in developed countries are affected with immune-based
      diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune
      diseases have shown increasing prevalences in the last decades. The role of
      chemical exposures in these phenomena is unclear. It is thought that the
      developmental immune system is more susceptible to toxicants than the mature
      situation. Developmental immunotoxicity (DIT) testing is nowadays not or
      minimally included in regulatory toxicology requirements. We reviewed whether
      developmental immune parameters in rodents would provide relatively sensitive
      endpoints of toxicity, whose inclusion in regulatory toxicity testing might
      improve hazard identification and risk assessment of chemicals. For each of the
      nine reviewed toxicants, the developing immune system was found to be at least as
      sensitive or more sensitive than the general (developmental) toxicity parameters.
      Functional immune (antigen-challenged) parameters appear more affected than
      structural (non-challenged) immune parameters. Especially, antibody responses to
      immune challenges with keyhole limpet hemocyanine or sheep red blood cells and
      delayed-type hypersensitivity responses appear to provide sensitive parameters of
      developmental immune toxicity. Comparison with current tolerable daily intakes
      (TDI) and their underlying overall no observed adverse effect levels showed that
      for some of the compounds reviewed, the TDI may need reconsideration based on
      developmental immune parameters. From these data, it can be concluded that the
      developing immune system is very sensitive to the disruption of toxicants
      independent of study design. Consideration of including functional DIT parameters
      in current hazard identification guidelines and wider application of relevant
      study protocols is warranted.

PMID- 25372702
TI  - What can comparative effectiveness research contribute to integrative health in
      international perspective?
AB  - The interest in Comparative Effectiveness Research (CER) in the international
      community is growing. A panel titled "What Can Comparative Effectiveness Research
      Contribute to Integrative Health in International Perspective?" took place at the
      3rd International Research Congress on Integrative Medicine and Health in
      Portland, Oregon, in 2012. The presentations at this panel highlighted different
      perspectives on CER, including the funders' and the stakeholders' perspectives
      from the United States, as well as experiences with economic evaluations from
      Australia and pragmatic trials in Europe. The funders' perspective emphasized the
      need for innovation and controlling costs in large-scale studies. The
      stakeholder's perspective stressed the need to gather the input of stakeholders
      in shaping the framework for more informative, more decision-maker-driven
      research. Several examples of cost-effectiveness analyses were offered from
      Australia. The importance of balancing rigor and pragmatism was also discussed in
      a presentation of the efficacy-effectiveness continuum. A wide-ranging discussion
      explored additional questions concerning the translation of evidence into
      practice; the effect of pragmatic trials on funding or policy; evidentiary
      distinctions between and among pragmatic trials and traditional randomized
      clinical trials; and the multiple roles of stakeholders, particularly in
      generating new information and knowledge. The presentations and discussions
      showed that more development of methods is needed. This includes developments on
      study design and statistical approaches, as well as methods for stakeholder
      involvement and mechanisms to bring these results into practice.

PMID- 25372703
TI  - Increasing disparities in the age-related incidences of colon and rectal cancers
      in the United States, 1975-2010.
AB  - IMPORTANCE: The overall incidence of colorectal cancer (CRC) has been decreasing
      since 1998 but there has been an apparent increase in the incidence of CRC in
      young adults. OBJECTIVE: To evaluate age-related disparities in secular trends in
      CRC incidence in the United States. DESIGN, SETTING, AND PATIENTS: A
      retrospective cohort study using the Surveillance, Epidemiology, and End Results
      (SEER) CRC registry. Age at diagnosis was analyzed in 15-year intervals starting
      at the age of 20 years. SEER*Stat was used to obtain the annual cancer incidence
      rates, annual percentage change, and corresponding P values for the secular
      trends. Data were obtained from the National Cancer Institute's SEER registry for
      all patients diagnosed as having colon or rectal cancer from January 1, 1975,
      through December 31, 2010 (N = 393 241). MAIN OUTCOME AND MEASURE: Difference in
      CRC incidence by age. RESULTS: The overall age-adjusted CRC incidence rate
      decreased by 0.92% (95% CI, -1.14 to -0.70) between 1975 and 2010. There has been
      a steady decline in the incidence of CRC in patients age 50 years or older, but
      the opposite trend has been observed for young adults. For patients 20 to 34
      years, the incidence rates of localized, regional, and distant colon and rectal
      cancers have increased. An increasing incidence rate was also observed for
      patients with rectal cancer aged 35 to 49 years. Based on current trends, in
      2030, the incidence rates for colon and rectal cancers will increase by 90.0% and
      124.2%, respectively, for patients 20 to 34 years and by 27.7% and 46.0%,
      respectively, for patients 35 to 49 years. CONCLUSIONS AND RELEVANCE: There has
      been a significant increase in the incidence of CRC diagnosed in young adults,
      with a decline in older patients. Further studies are needed to determine the
      cause for these trends and identify potential preventive and early detection
      strategies.

PMID- 25372704
TI  - Genome wide association study of fetal hemoglobin in sickle cell anemia in
      Tanzania.
AB  - BACKGROUND: Fetal hemoglobin (HbF) is an important modulator of sickle cell
      disease (SCD). HbF has previously been shown to be affected by variants at three
      loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to
      be discovered. METHODS AND FINDINGS: We conducted a genome-wide association study
      (GWAS) in 1,213 SCA (HbSS/HbSbeta0) patients in Tanzania. Genotyping was done
      with Illumina Omni2.5 array and imputation using 1000 Genomes Phase I release
      data. Association with HbF was analysed using a linear mixed model to control for
      complex population structure within our study. We successfully replicated known
      associations for HbF near BCL11A and the HBS1L-MYB intergenic polymorphisms
      (HMIP), including multiple independent effects near BCL11A, consistent with
      previous reports. We observed eight additional associations with P<10(-6). These
      associations could not be replicated in a SCA population in the UK. CONCLUSIONS:
      This is the largest GWAS study in SCA in Africa. We have confirmed known
      associations and identified new genetic associations with HbF that require
      further replication in SCA populations in Africa.

PMID- 25372705
TI  - Integrating sustainable hunting in biodiversity protection in Central Africa: hot
      spots, weak spots, and strong spots.
AB  - Wild animals are a primary source of protein (bushmeat) for people living in or
      near tropical forests. Ideally, the effect of bushmeat harvests should be
      monitored closely by making regular estimates of offtake rate and size of stock
      available for exploitation. However, in practice, this is possible in very few
      situations because it requires both of these aspects to be readily measurable,
      and even in the best case, entails very considerable time and effort. As
      alternative, in this study, we use high-resolution, environmental favorability
      models for terrestrial mammals (N = 165) in Central Africa to map areas of high
      species richness (hot spots) and hunting susceptibility. Favorability models
      distinguish localities with environmental conditions that favor the species'
      existence from those with detrimental characteristics for its presence. We
      develop an index for assessing Potential Hunting Sustainability (PHS) of each
      species based on their ecological characteristics (population density, habitat
      breadth, rarity and vulnerability), weighted according to restrictive and
      permissive assumptions of how species' characteristics are combined. Species are
      classified into five main hunting sustainability classes using fuzzy logic. Using
      the accumulated favorability values of all species, and their PHS values, we
      finally identify weak spots, defined as high diversity regions of especial
      hunting vulnerability for wildlife, as well as strong spots, defined as high
      diversity areas of high hunting sustainability potential. Our study uses
      relatively simple models that employ easily obtainable data of a species'
      ecological characteristics to assess the impacts of hunting in tropical regions.
      It provides information for management by charting the geography of where species
      are more or less likely to be at risk of extinction from hunting.

PMID- 25372706
TI  - Antibacterial activity and kinetics of Litsea cubeba oil on Escherichia coli.
AB  - Litsea cubeba oil is extracted from the fresh fruits of Litsea cubeba by
      distillation. In this study, its chemical constituents, antibacterial activity,
      kinetics and effects against Escherichia coli were studied. Its minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were
      both 0.125% (v/v) by toxic food method. Moreover, the antibacterial kinetic
      curves indicated 0.0625% (v/v) of litsea cubeba oil was able to prolong the
      growth lag phase of E. coli cells to approximate 12 hours while 0.125% (v/v) of
      litsea cubeba oil was able to kill the cells completely. Furthermore,
      transmission electron microscope (TEM) observation showed most E. coli cells
      treated with 0.125% (v/v) of litsea cubeba oil were killed or destroyed severely
      within 2 hours. The litsea cubeba oil might penetrate and destroy the outer and
      inner membrane of E. coli cells. Thus many holes and gaps were observed on the
      damaged cells, which led to their death eventually. The antibacterial effects of
      litsea cubeba oil mainly attributed to the presence of aldehydes, which accounted
      for approximately 70% in its whole components analyzed by GC/MS. Based on the
      antimicrobial properties, litsea cubeba oil would have a broad application in the
      antimicrobial industry. 

PMID- 25372707
TI  - Factors influencing superimposition error of 3D cephalometric landmarks by plane
      orientation method using 4 reference points: 4 point superimposition error
      regression model.
AB  - Superimposition has been used as a method to evaluate the changes of orthodontic
      or orthopedic treatment in the dental field. With the introduction of cone beam
      CT (CBCT), evaluating 3 dimensional changes after treatment became possible by
      superimposition. 4 point plane orientation is one of the simplest ways to achieve
      superimposition of 3 dimensional images. To find factors influencing
      superimposition error of cephalometric landmarks by 4 point plane orientation
      method and to evaluate the reproducibility of cephalometric landmarks for
      analyzing superimposition error, 20 patients were analyzed who had normal
      skeletal and occlusal relationship and took CBCT for diagnosis of
      temporomandibular disorder. The nasion, sella turcica, basion and midpoint
      between the left and the right most posterior point of the lesser wing of
      sphenoidal bone were used to define a three-dimensional (3D) anatomical reference
      co-ordinate system. Another 15 reference cephalometric points were also
      determined three times in the same image. Reorientation error of each landmark
      could be explained substantially (23%) by linear regression model, which consists
      of 3 factors describing position of each landmark towards reference axes and
      locating error. 4 point plane orientation system may produce an amount of
      reorientation error that may vary according to the perpendicular distance between
      the landmark and the x-axis; the reorientation error also increases as the
      locating error and shift of reference axes viewed from each landmark increases.
      Therefore, in order to reduce the reorientation error, accuracy of all landmarks
      including the reference points is important. Construction of the regression model
      using reference points of greater precision is required for the clinical
      application of this model. 

PMID- 25372708
TI  - Health Care Indicators.
AB  - This regular feature of the journal includes a discussion of each of the
      following four topics community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25372709
TI  - The importance of body weight for the dose response relationship of oral vitamin
      D supplementation and serum 25-hydroxyvitamin D in healthy volunteers.
AB  - Unlike vitamin D recommendations by the Institute of Medicine, the Clinical
      Practice Guidelines by the Endocrine Society acknowledge body weight
      differentials and recommend obese subjects be given two to three times more
      vitamin D to satisfy their body's vitamin D requirement. However, the Endocrine
      Society also acknowledges that there are no good studies that clearly justify
      this. In this study we examined the combined effect of vitamin D supplementation
      and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy
      volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum
      25(OH)D from 17,614 healthy adult volunteers participating in a preventive health
      program. This program encourages the use of vitamin D supplementation and
      monitors its use and serum 25(OH)D and serum calcium levels. Participants
      reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had
      serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response
      relationship between vitamin D supplementation and serum 25(OH)D followed an
      exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000
      IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per
      1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI,
      relative to absolute body weight, was found to be the better determinant of
      25(OH)D. Relative to normal weight subjects, obese and overweight participants
      had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower,
      respectively (P<0.001). We did not observe any increase in the risk for
      hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D
      supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher
      for overweight subjects relative to normal weight subjects. This observational
      study provides body weight specific recommendations to achieve 25(OH)D targets. 

PMID- 25372710
TI  - Primary ovarian carcinomas and abdominal metastasis contain 4,6-disulfated
      chondroitin sulfate rich regions, which provide adhesive properties to tumour
      cells.
AB  - High mortality in ovarian cancer patients is primarily caused through rapid
      metastasis of the tumour, but the underlying mechanisms are poorly understood.
      Glycosaminoglycans, are abundantly present in tumours and chondroitin sulfate-E
      (CSE), a highly 4,6-sulfated glycosaminoglycan, has been indicated to play a role
      in carcinogenesis. In this study we investigated the presence of CSE in ovarian
      cancer metastasis and studied its role in tumour cell adhesiveness and migration.
      CSE was studied immunohistochemically in primary ovarian carcinomas and abdominal
      metastases using the single chain antibody GD3G7. The role of CSE was studied in
      2D (scratch assays) and 3D (collagen matrices, spheroids) systems using SKOV3
      cells applying 1: overexpression of CSE by stable transfection with DNA encoding
      GalNAc4S-6 sulfotransferase, 2: enzymatic removal of CS, and 3: addition of CSE.
      In ovarian cancer tissue, CSE expression was predominantly seen in the stromal
      compartment of both primary ovarian carcinomas and metastases, with a comparable
      degree of intensity and extent. Overexpression of CSE disaccharide units by
      tumour cells increased their adhesive properties which was especially seen in
      tumour spheroid formation. Increased expression of CSE reduced cell migration.
      Addition of free CSE had similar effects. The data presented here indicate that
      CSE is associated with metastatic lesions and that it provides tumours with
      adhesive properties. CSE rich motifs are put forward as a potential target for
      ovarian cancer therapy. 

PMID- 25372711
TI  - Identification of under-detected periodicity in time-series microarray data by
      using empirical mode decomposition.
AB  - Detecting periodicity signals from time-series microarray data is commonly used
      to facilitate the understanding of the critical roles and underlying mechanisms
      of regulatory transcriptomes. However, time-series microarray data are noisy. How
      the temporal data structure affects the performance of periodicity detection has
      remained elusive. We present a novel method based on empirical mode decomposition
      (EMD) to examine this effect. We applied EMD to a yeast microarray dataset and
      extracted a series of intrinsic mode function (IMF) oscillations from the time
      series data. Our analysis indicated that many periodically expressed genes might
      have been under-detected in the original analysis because of interference between
      decomposed IMF oscillations. By validating a protein complex coexpression
      analysis, we revealed that 56 genes were newly determined as periodic. We
      demonstrated that EMD can be used incorporating with existing periodicity
      detection methods to improve their performance. This approach can be applied to
      other time-series microarray studies. 

PMID- 25372712
TI  - Minerals in the foods eaten by mountain gorillas (Gorilla beringei).
AB  - Minerals are critical to an individual's health and fitness, and yet little is
      known about mineral nutrition and requirements in free-ranging primates. We
      estimated the mineral content of foods consumed by mountain gorillas (Gorilla
      beringei beringei) in the Bwindi Impenetrable National Park, Uganda. Mountain
      gorillas acquire the majority of their minerals from herbaceous leaves, which
      constitute the bulk of their diet. However, less commonly eaten foods were
      sometimes found to be higher in specific minerals, suggesting their potential
      importance. A principal component analysis demonstrated little correlation among
      minerals in food items, which further suggests that mountain gorillas might
      increase dietary diversity to obtain a full complement of minerals in their diet.
      Future work is needed to examine the bioavailability of minerals to mountain
      gorillas in order to better understand their intake in relation to estimated
      needs and the consequences of suboptimal mineral balance in gorilla foods. 

PMID- 25372713
TI  - Mechanistic investigation of ion migration in Na3V2(PO4)2F3 hybrid-ion batteries.
AB  - The ion-migration mechanism of Na3V2(PO4)2F3 is investigated in Na3V2(PO4)2F3-Li
      hybrid-ion batteries for the first time through a combined computational and
      experimental study. There are two Na sites namely Na(1) and Na(2) in
      Na3V2(PO4)2F3, and the Na ions at Na(2) sites with 0.5 occupation likely extract
      earlier to form Na2V2(PO4)2F3. The structural reorganisation is suggested to make
      a stable configuration of the remaining ions at the centre of Na(1) sites. After
      the extraction of the second Na ion, the last ion prefers to change occupation
      from 1 to 0.5 to occupy two Na(2) sites. The insertion of predominant Li ions
      also should undergo structural reorganization when the first Li ion inserts into
      the centre of Na(1) site theoretically forming NaLiV2(PO4)2F3, and the second ion
      inserts into two Na(2) sites to form NaLi2V2(PO4)2F3. More than a 0.3 Li ion
      insertion would take place in the applied voltage range by increasing the number
      of sites occupied rather than occupy the vacancy in triangular prismatic sites.
      An improved solution-based carbothermal reduction methodology makes Na3V2(PO4)2F3
      exhibit excellent C-rate and cycling performances, of which the Li-inserted
      voltage is evaluated by first principles calculations. 

PMID- 25372719
TI  - Patterns and variability of projected bioclimatic habitat for Pinus albicaulis in
      the Greater Yellowstone Area.
AB  - Projected climate change at a regional level is expected to shift vegetation
      habitat distributions over the next century. For the sub-alpine species whitebark
      pine (Pinus albicaulis), warming temperatures may indirectly result in loss of
      suitable bioclimatic habitat, reducing its distribution within its historic
      range. This research focuses on understanding the patterns of spatiotemporal
      variability for future projected P.albicaulis suitable habitat in the Greater
      Yellowstone Area (GYA) through a bioclimatic envelope approach. Since intermodel
      variability from General Circulation Models (GCMs) lead to differing predictions
      regarding the magnitude and direction of modeled suitable habitat area, nine bias
      corrected statistically down-scaled GCMs were utilized to understand the
      uncertainty associated with modeled projections. P.albicaulis was modeled using a
      Random Forests algorithm for the 1980-2010 climate period and showed strong
      presence/absence separations by summer maximum temperatures and springtime
      snowpack. Patterns of projected habitat change by the end of the century
      suggested a constant decrease in suitable climate area from the 2010 baseline for
      both Representative Concentration Pathways (RCPs) 8.5 and 4.5 climate forcing
      scenarios. Percent suitable climate area estimates ranged from 2-29% and 0.04-10%
      by 2099 for RCP 8.5 and 4.5 respectively. Habitat projections between GCMs
      displayed a decrease of variability over the 2010-2099 time period related to
      consistent warming above the 1910-2010 temperature normal after 2070 for all
      GCMs. A decreasing pattern of projected P.albicaulis suitable habitat area change
      was consistent across GCMs, despite strong differences in magnitude. Future
      ecological research in species distribution modeling should consider a full suite
      of GCM projections in the analysis to reduce extreme range
      contractions/expansions predictions. The results suggest that restoration
      strageties such as planting of seedlings and controlling competing vegetation may
      be necessary to maintain P.albicaulis in the GYA under the more extreme future
      climate scenarios. 

PMID- 25372714
TI  - NPRL-Z-1, as a new topoisomerase II poison, induces cell apoptosis and ROS
      generation in human renal carcinoma cells.
AB  - NPRL-Z-1 is a 4beta-[(4"-benzamido)-amino]-4'-O-demethyl-epipodophyllotoxin
      derivative. Previous reports have shown that NPRL-Z-1 possesses anticancer
      activity. Here NPRL-Z-1 displayed cytotoxic effects against four human cancer
      cell lines (HCT 116, A549, ACHN, and A498) and exhibited potent activity in A498
      human renal carcinoma cells, with an IC50 value of 2.38 uM via the MTT assay. We
      also found that NPRL-Z-1 induced cell cycle arrest in G1-phase and detected DNA
      double-strand breaks in A498 cells. NPRL-Z-1 induced ataxia telangiectasia
      mutated (ATM) protein kinase phosphorylation at serine 1981, leading to the
      activation of DNA damage signaling pathways, including Chk2, histone H2AX, and
      p53/p21. By ICE assay, the data suggested that NPRL-Z-1 acted on and stabilized
      the topoisomerase II (TOP2)-DNA complex, leading to TOP2cc formation. NPRL-Z-1
      induced DNA damage signaling and apoptotic death was also reversed by TOP2alpha
      or TOP2beta knockdown. In addition, NPRL-Z-1 inhibited the Akt signaling pathway
      and induced reactive oxygen species (ROS) generation. These results demonstrated
      that NPRL-Z-1 appeared to be a novel TOP2 poison and ROS generator. Thus, NPRL-Z
      1 may present a significant potential anticancer candidate against renal
      carcinoma.

PMID- 25372720
TI  - Malaria mosquitoes host-locate and feed upon caterpillars.
AB  - Adult female mosquitoes need blood to develop their eggs and both sexes use
      nectar and honeydew as carbohydrate resources for flight, survival and to enhance
      reproduction. However, there are also a few reports in the literature of
      mosquitoes feeding on haemolymph of soft-bodied insects such as caterpillars. The
      frequency and significance of this entomophagous behavior is not well understood,
      but is thought to be a vestige of ancestral feeding behavior or an opportunistic
      behavior that has evolved over time. In our current paper we investigated the
      extent to which the malaria mosquito, Anopheles stephensi, is attracted to, and
      can successfully feed on, larvae of two common moth species, Manduca sexta and
      Heliothis subflexa. Using y-tube olfactometer assays we found that female An.
      stephensi readily flew upwind to and landed on the caterpillars of both moth
      species. The nature of the volatile cues used in host location remains unclear
      but respirometer studies suggest a possible role of CO2. Laboratory cage assays
      further showed that the female mosquitoes were able to actively feed on moth
      larvae and gain sufficient nutritional benefit to influence survival. The extent
      to which such an opportunistic behavior occurs in the field has yet to be
      explored but our results suggest that this haemolymph feeding behavior could play
      a role in malaria mosquito life history and could provide a novel mechanism for
      horizontal transmission of pathogens and other micro-organisms between hosts. 

PMID- 25372721
TI  - Assessment of the effectiveness of supply-side cost-containment measures.
AB  - This article assesses the arguments and evidence concerning the likely
      effectiveness of four supply-side cost-containment measures. The health planning
      efforts of the 1970s, particularly certificate-of-need regulations, had very
      limited success in containing costs. The new and related tools of technology
      assessment and practice guidelines hold some promise for refining benefit
      packages, but they are inadequate for micromanaging complex medical practices.
      Payment policies, such as hospital ratesetting, have enjoyed some success in
      limiting hospital cost growth but are less effective at controlling total costs.
      None of these measures alone is likely to address fully the fundamental issues of
      equity and efficiency in health care resource allocation that underlie the
      problem of rising costs.

PMID- 25372724
TI  - Comparison between BNP values measured in capillary blood samples with a POCT
      method and those measured in plasma venous samples with an automated platform.

PMID- 25372725
TI  - Pathophysiology of adipose tissue: effects of steroid hormones. Part C.

PMID- 25372723
TI  - A transcervical amniotic fluid collector: a new medical device for the assessment
      of amniotic fluid in patients with ruptured membranes.
AB  - AIM: To describe a new device for the transcervical collection of amniotic fluid
      (AF) in patients with ruptured membranes, and to compare the concentration of
      proteins in fluid retrieved by transabdominal amniocentesis and the transcervical
      AF collector. STUDY DESIGN: Paired AF samples were collected in patients with
      preterm prelabor rupture of membranes (PROM) (n=11) by transabdominal
      amniocentesis and with the transcervical AF collector (Yoon's AF CollectorTM).
      Three proteins known to have high concentrations in AF [alpha-fetoprotein (AFP),
      beta-human chorionic gonadotrophin (beta-hCG), and prolactin] were measured.
      RESULTS: (1) There was a significant correlation between the concentrations of
      analytes in AF obtained by transabdominal amniocentesis and by the transcervical
      AF collector (r=0.94, P<0.001 for AFP; r=0.96, P<0.001 for beta-hCG; r=0.72,
      P<0.05 for prolactin); (2) Bland-Altman plots showed no evidence of
      heteroscedasticity between transabdominal or transcervical AF concentrations of
      these markers. CONCLUSIONS: There was a strong correlation between the
      concentrations of proteins in AF collected by amniocentesis or with the
      transcervical device.

PMID- 25372726
TI  - Adipose tissue inflammation and cancer cachexia: the role of steroid hormones.
AB  - Adipose tissue inflammation plays a role in the etiology of many chronic
      diseases, and has been the focus of much attention in the context of obesity and
      metabolic syndrome. Similarly, during cancer cachexia, a syndrome that markedly
      increases cancer-associated morbidity and mortality, local adipose inflammation
      is reported in animal models and in patients, potentially contributing to the
      chronic systemic inflammation that constitutes the hallmark of this condition. We
      discuss, on the basis of information generated by obesity-related studies, the
      possible relation between adipose tissue inflammation and compromised steroid
      hormone secretion and action in cachexia.

PMID- 25372727
TI  - Detrimental and protective fat: body fat distribution and its relation to
      metabolic disease.
AB  - Obesity is linked to numerous comorbidities that include, but are not limited to,
      glucose intolerance, insulin resistance, dyslipidemia, and cardiovascular
      disease. Current evidence suggests, however, obesity itself is not an exclusive
      predictor of metabolic dysregulation but rather adipose tissue distribution.
      Obesity-related adverse health consequences occur predominately in individuals
      with upper body fat accumulation, the detrimental distribution, commonly
      associated with visceral obesity. Increased lower body subcutaneous adipose
      tissue, however, is associated with a reduced risk of obesity-induced metabolic
      dysregulation and even enhanced insulin sensitivity, thus, storage in this region
      is considered protective. The proposed mechanisms that causally relate the
      differential outcomes of adipose tissue distribution are often attributed to
      location and/or adipocyte regulation. Visceral adipose tissue effluent to the
      portal vein drains into the liver where hepatocytes are directly exposed to its
      metabolites and secretory products, whereas the subcutaneous adipose tissue
      drains systemically. Adipose depots are also inherently different in numerous
      ways such as adipokine release, immunity response and regulation, lipid turnover,
      rate of cell growth and death, and response to stress and sex hormones. Proximal
      extrinsic factors also play a role in the differential drive between adipose
      tissue depots. This review focuses on the deleterious mechanisms postulated to
      drive the differential metabolic response between central and lower body adipose
      tissue distribution.

PMID- 25372728
TI  - Sleep disturbances, body fat distribution, food intake and/or energy expenditure:
      pathophysiological aspects.
AB  - Data from cross-sectional and longitudinal studies have illustrated a
      relationship between short sleep duration (SSD) and weight gain. Individuals with
      SSD are heavier and gain more weight over time than normal-duration sleepers.
      This sleep-obesity relationship may have consequences for obesity treatments, as
      it appears that short sleepers have reduced ability to lose weight. Laboratory
      based clinical studies found that experimental sleep restriction affects energy
      expenditure and intake, possibly providing a mechanistic explanation for the
      weight gain observed in chronic short sleepers. Specifically, compared to normal
      sleep duration, sleep restriction increases food intake beyond the energetic
      costs of increased time spent awake. Reasons for this increased energy intake
      after sleep restriction are unclear but may include disrupted appetite-regulating
      hormones, altered brain mechanisms involved in the hedonic aspects of appetite,
      and/or changes in sleep quality and architecture. Obstructive sleep apnea (OSA)
      is a disorder at the intersection of sleep and obesity, and the characteristics
      of the disorder illustrate many of the effects of sleep disturbances on body
      weight and vice versa. Specifically, while obesity is among the main risk factors
      for OSA, the disorder itself and its associated disturbances in sleep quality and
      architecture seem to alter energy balance parameters and may induce further
      weight gain. Several intervention trials have shown that weight loss is
      associated with reduced OSA severity. Thus, weight loss may improve sleep, and
      these improvements may promote further weight loss. Future studies should
      establish whether increasing sleep duration/improving sleep quality can induce
      weight loss.

PMID- 25372729
TI  - Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal
      regulation for osteoporosis and obesity development.
AB  - The belief that obesity is protective against osteoporosis has recently been
      revised. In fact, the latest epidemiologic and clinical studies show that a high
      level of fat mass, but also reduced muscle mass, might be a risk factor for
      osteoporosis and fragility fractures. Furthermore, increasing evidence seems to
      indicate that different components such as myokines, adipokines and growth
      factors, released by both fat and muscle tissues, could play a key role in the
      regulation of skeletal health and in low bone mineral density and, thus, in
      osteoporosis development. This review considers old and recent data in the
      literature to further evaluate the relationship between fat, bone and muscle
      tissue.

PMID- 25372730
TI  - Obesity and the gut microbiome: pathophysiological aspects.
AB  - While there is a large volume of literature describing a role for obesity as a
      risk factor for breast cancer and many other cancers, in the main a causal
      relationship has not been established. If the study is limited to breast cancer
      risk, it has been suggested that the increase in sex steroid formation that
      occurs in postmenopausal women plays a role. Obesity is known to be associated
      with chronic low grade inflammation, but no reason for this association has been
      offered in the past. The gut microbiome, while known to be enormous, has not in
      the past been considered as a metabolic role player in the body. This is now
      recognized to be the case. Recent studies have found the obesity is correlated
      with an alteration in the gut microbiome. In obese individual there is a change
      in the relative proportions of the two major classes of bacteria - bacteroides
      and firmacutes - with the latter dominant in obesity and resulting in the
      formation of increased amounts of metabolic endotoxins like deoxycholic acid and
      lipopolysaccharides (LPS). Obese individuals show a decrease in the concentration
      of Akkermansia muciniphila in the mucus that lines the intestinal wall, resulting
      in thinner mucus and a weakened intestinal lining and permitting metabolic
      endotoxins formed by other bacterial flora like LPS to enter the blood steam and
      cause the chronic inflammation associated with obesity. The change in the
      microbiome profile results in increases in bacterial strains that are more
      efficient at generating energy, leading to increased obesity. In mice, it has
      been shown that introducing gut bacterial flora from the cecum of obese mice into
      germ-free mice results in increased obesity with lesser food consumption while
      the reverse, introducing bacterial flora from lean mice results in a loss in
      weight. This raises the attractive possibility that manipulating the gut
      microbiome could facilitate weight loss or prevent obesity in humans.

PMID- 25372731
TI  - Cross-talk between adipose tissue and the HPA axis in obesity and overt
      hypercortisolemic states.
AB  - In addition to its roles in providing insulation and mechanical support, adipose
      tissue (AT) has been recognised as the major site for storage of surplus fuel.
      Since leptin was discovered, white AT (WAT) has been recognised as an endocrine
      organ and an important source of biologically active substances with local and/or
      systemic action called adipokines. The metabolic and endocrine activities of AT
      are under the control of several hormones: a particular role has been played by
      glucocorticoids (GC), which able to participate, along with other hormones, both
      in recruitment of progenitor cells and in differentiation and secretive
      activities. AT is also able to generate cortisol from cortisone through 11beta
      hydroxysteroid-dehydrogenase (11beta-HSD). There are controversial reports in the
      literature, showing a hyperactivity of 11beta-HSD in obesity. It has been
      postulated that obesity, particularly the visceral body fat distribution (V-BFD),
      may be considered a maladaptation to stress exposure, thus leading to
      hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, and higher-than
      normal cortisol levels. In this review, we will examine the cross-talk between
      the HPA axis and AT, their relationship under stressful events, depending on
      steroid hormones and different adipokine secretions.

PMID- 25372732
TI  - Circulating and adipose tissue matrix metalloproteinases in cardiometabolic risk
      environments: pathophysiological aspects.
AB  - Matrix metalloproteinases (MMPs) play an important role during physiological
      tissue remodeling in embryonic development and angiogenesis, as well as in
      pathophysiological conditions such as obesity and development and vulnerability
      of atherosclerotic plaque. Moreover, MMP circulating levels have emerged as
      potential biomarkers of cardiovascular disease. MMP expression and activity are
      regulated by different factors such as insulin resistance and obesity. Expanded
      fat tissue has been demonstrated to be an active organ, where MMPs also exert a
      role in adipogenesis, angiogenesis, and proliferation of extracellular matrix
      (ECM). However, the lack of association between adipose tissue and plasma levels
      of some MMPs, specifically MMP-2 and MMP-9, suggests that this tissue is not a
      major contributor to circulating gelatinases. MMPs are also co-expressed or co
      repressed in response to inflammatory adipocytokines, like adiponectin and
      leptin. Adiponectin may also play a protective role in plaque rupture through
      selectively increasing the tissue inhibitor of metalloproteinase (TIMP)
      expression. Leptin induces the expression of MMP-2 activators as well as the
      expression of MMP-2, MMP-9, and TIMP-1 in different human cells. Furthermore, sex
      hormones also participate in MMP regulation. In postmenopausal women, hormone
      replacement therapy produces an increase in MMP activity, leading to a breakdown
      in ECM homeostasis and accelerated progression of vascular pathologies. Besides,
      in men, an inverse relationship between testosterone levels and MMP-2 activity
      has been described. It is still necessary to go forward in the study of MMPs in
      different metabolic situations to corroborate their role as vulnerable plaque
      biomarkers.

PMID- 25372733
TI  - Sex hormone imbalances and adipose tissue dysfunction impacting on metabolic
      syndrome; a paradigm for the discovery of novel adipokines.
AB  - Sex hormone imbalance is causally related with visceral adipose tissue (AT)
      dysfunction and visceral obesity - an etiological component of metabolic syndrome
      (MetS), associated with high risk of both cardiovascular disease (CVD) and type 2
      diabetes. In general, premenopausal women appear to be protected from CVD and the
      dramatic decline in sex steroid hormone occurring during menopausal transitions
      or other sex-related disorders influence the regional distribution, function, and
      metabolism of AT and increase the risk of CVD. Visceral AT dysfunction,
      manifesting as abnormality of fatty acid metabolism, increased oxidative stress,
      endothelial dysfunction, and excessive production of adipokines have been
      proposed in the pathogenesis of MetS. However, direct evidence of molecular
      mechanisms of depot-specific AT alterations, and dysfunction causally related to
      MetS is limited in studies on postmenopausal women due to difficulty in
      collecting discrete AT specimens at different ages and repeated sampling from
      different fat depots. This can be overcome using animal models that can mimic the
      cluster of pathology leading to MetS and help establish the molecular basis of
      links between loss of gonadal function on various AT depots and their
      contribution to MetS. Our group used sex hormone imbalance FSH receptor knock out
      (FORKO) female mice to recapitulate different aspects of the MetS and addressed
      the mechanism of visceral obesity related to MetS and discover two novel sex
      steroid hormone-regulated deep mesenteric estrogen-dependent adipose (MEDAs)
      genes. Taken together, such recent studies raise hopes for pharmacologic
      intervention strategies targeting sex steroid hormone signaling in AT to provide
      protection against AT dysfunction.

PMID- 25372734
TI  - Estradiol regulates insulin signaling and inflammation in adipose tissue.
AB  - BACKGROUND: Obesity-associated low-grade inflammation at white adipose tissue
      (WAT) leads to metabolic defects. Sex steroid hormone estrogen may be protective
      against high-fat diet (HFD)-induced obesity and insulin resistance. This has been
      tested by many previous studies utilizing rodent models of ovariectomy (OVX)
      and/or treatment of estradiol (E2), the major biologically active form of
      estrogen. Body weight and adiposity are increased by OVX and reduced following E2
      treatment, however. Thus, the protective roles of E2 may be secondary effects to
      the changes in body weight and adiposity. We hypothesize that E2 directly
      prevents inflammation and maintains insulin sensitivity in WAT independent of
      energy status using mice with similar body weights and adiposity. MATERIALS AND
      METHODS: Four groups of female C57BL/6 mice were used, including sham-operated
      mice treated with vehicle for E2 and fed with either a low-fat diet (LFD; Sham
      Veh-LFD) or a HFD (Sham-Veh-HFD), and HFD-fed OVX mice treated with either
      vehicle (OVX-Veh-HFD) or E2 (OVX-E2-HFD). Body weight and abdominal parametrial
      WAT mass, insulin signaling, and expression levels of genes related to low-grade
      inflammation in WAT were compared between these groups pair-fed with equal
      amounts of calories for a period of 4 days. RESULTS: Body weights and WAT mass
      were similar in all four groups. OVX-Veh-HFD mice had impaired insulin signaling
      associated with rapid activation of inflammation, whereas OVX-E2-HFD group
      maintained insulin sensitivity without showing inflammation in WAT. CONCLUSIONS:
      E2 directly contributed to the maintenance of insulin sensitivity during the
      early phase of development of metabolic dysfunction, possibly via preventing low
      grade inflammation in WAT.

PMID- 25372736
TI  - Energy metabolism and hindbrain AMPK: regulation by estradiol.
AB  - Nerve cell energy status is screened within multiple classically defined
      hypothalamic and hindbrain components of the energy balance control network,
      including the hindbrain dorsal vagal complex (DVC). Signals of caudal DVC origin
      have a physiological role in glucostasis, e.g., maintenance of optimal supply of
      the critical substrate fuel, glucose, through control of motor functions such as
      fuel consumption and gluco-counterregulatory hormone secretion. A2 noradrenergic
      neurons are a likely source of these signals as combinatory laser
      microdissection/high-sensitivity Western blotting reveals expression of multiple
      biomarkers for metabolic sensing, including adenosine 5'-monophosphate-activated
      protein kinase (AMPK). Hypoglycemia elicits estradiol-dependent sex differences
      in A2 AMPK activation as phospho-AMPK (pAMPK) expression is augmented in male and
      ovariectomized (OVX) female, but not estrogen-replaced, OVX rats. This dichotomy
      may reflect, in part, estradiol-mediated up-regulation of glycolytic and
      tricarboxylic acid cycle enzyme expression during hypoglycemia. Our new model for
      short-term feeding abstinence has physiological relevance to planned (dieting) or
      unplanned (meal delay) interruption of consumption in modern life, which is
      negatively correlated with appetite control and obesity, and is useful for
      investigating how estrogen may mitigate the effects of disrupted fuel acquisition
      on energy balance via actions within the DVC. Estradiol reduces DVC AMPK activity
      after local delivery of the AMP mimic, 5-aminoimidazole-4-carboxamide-riboside,
      or cessation of feeding for 12 h but elevates pAMPK expression when these
      treatments are combined. These data suggest that estrogen maintains cellular
      energy stability over periods of suspended fuel acquisition and yet optimizes, by
      DVC AMPK-dependent mechanisms, counter-regulatory responses to metabolic
      challenges that occur during short-span feeding abstinence.

PMID- 25372737
TI  - Endocrine disruptors and polycystic ovary syndrome: a focus on Bisphenol A and
      its potential pathophysiological aspects.
AB  - Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of unknown etiology
      that may arise from a combination of a number of underlying genetic interactions
      and predispositions with environmental factors. Endocrine disruptors and, in
      particular, Bisphenol A may represent one of the many underlying causes of the
      syndrome as they are experimentally linked to metabolic and reproductive
      derangements resembling PCOS-related disorders. Exposure to endocrine-disrupting
      chemicals may act as an environmental modifier to worsen symptoms of PCOS in
      affected females or to contribute to the final phenotype of the syndrome in
      genetically predisposed individuals.

PMID- 25372738
TI  - The convergence of autophagy, small RNA and the stress response - implications
      for transgenerational epigenetic inheritance in plants.
AB  - Recent discoveries in eukaryotes have shown that autophagy-mediated degradation
      of DICER and ARGONAUTE (AGO), the proteins involved in post-transcriptional gene
      silencing (PTGS), can occur in response to viral infection and starvation. In
      plants, a virally encoded protein P0 specifically interacts with AGO1 and
      enhances degradation through autophagy, resulting in suppression of gene
      silencing. In HeLa cells, DICER and AGO2 protein levels decreased after nutrient
      starvation or after treatment to increase autophagy. Environmental exposures to
      viral infection and starvation have also recently been shown to sometimes not
      only induce a stress response in the exposed plant but also in their unexposed
      progeny. These, and other cases of inherited stress response in plants are
      thought to be facilitated through transgenerational epigenetic inheritance, and
      the mechanism involves the PTGS and transcriptional gene silencing (TGS)
      pathways. These recent discoveries suggest that the environmentally-induced
      autophagic degradation of the PTGS and TGS components may have significant
      effects on inherited stress responses.

PMID- 25372735
TI  - Cross-talk between reproduction and energy homeostasis: central impact of
      estrogens, leptin and kisspeptin signaling.
AB  - The central nervous system receives hormonal cues (e.g., estrogens and leptin,
      among others) that influence reproduction and energy homeostasis. 17beta
      estradiol (E2) is known to regulate gonadotropin-releasing hormone (GnRH)
      secretion via classical steroid signaling and rapid non-classical membrane
      initiated signaling. Because GnRH neurons are void of leptin receptors, the
      actions of leptin on these neurons must be indirect. Although it is clear that
      the arcuate nucleus of the hypothalamus is the primary site of overlap between
      these two systems, it is still unclear which neural network(s) participate in the
      cross-talk of E2 and leptin, two hormones essential for reproductive function and
      metabolism. Herein we review the progress made in understanding the interactions
      between reproduction and energy homeostasis by focusing on the advances made to
      understand the cellular signaling of E2 and leptin on three neural networks:
      kisspeptin, pro-opiomelanocortin (POMC) and neuropeptide Y (NPY). Although
      critical in mediating the actions of E2 and leptin, considerable work still
      remains to uncover how these neural networks interact in vivo.

PMID- 25372740
TI  - Dynamical perspective of protein-DNA interaction.
AB  - The interactions between protein-DNA are essential for various biological
      activities. In this review, we provide an overview of protein-DNA interactions
      that emphasizes the importance of dynamical aspects. We divide protein-DNA
      interactions into two categories: nonspecific and specific and both the
      categories would be discussed highlighting some of our relevant work. In the case
      of nonspecific protein-DNA interaction, solvation studies (picosecond and
      femtosecond-resolved) explore the role environmental dynamics and change in the
      micropolarity around DNA molecules upon complexation with histone protein (H1).
      While exploring the specific protein-DNA interaction at lambda-repressor-operator
      sites interaction, particularly OR1 and OR2, it was observed that the interfacial
      water dynamics is minimally perturbed upon interaction with DNA, suggesting the
      labile interface in the protein-DNA complex. Forster resonance energy transfer
      (FRET) study revealed that the structure of the protein is more compact in
      repressor-OR2 complex than in the repressor-OR1 complex. Fluorescence anisotropy
      studies indicated enhanced flexibility of the C-terminal domain of the repressor
      at fast timescales after complex formation with OR1. The enhanced flexibility and
      different conformation of the C-terminal domain of the repressor upon
      complexation with OR1 DNA compared to OR2 DNA were found to have pronounced
      effect on the rate of photoinduced electron transfer.

PMID- 25372739
TI  - The MDM2 gene family.
AB  - MDM2 is an oncoprotein that blocks p53 tumor suppressor-mediated transcriptional
      transactivation, escorts p53 from the cell nucleus to the cytoplasm, and
      polyubiquitylates p53. Polyubiquitylated p53 is rapidly degraded in the cytoplasm
      by the 26S proteasome. MDM2 is abnormally upregulated in several types of
      cancers, especially those of mesenchymal origin. MDM4 is a homolog of MDM2 that
      also inhibits p53 by blocking p53-mediated transactivation. MDM4 is required for
      MDM2-mediated polyubiquitylated of p53 and is abnormally upregulated in several
      cancer types. MDM2 and MDM4 genes have been detected in all vertebrates to date
      and only a single gene homolog, named MDM, has been detected in some
      invertebrates. MDM2, MDM4, and MDM have similar gene structures, suggesting that
      MDM2 and MDM4 arose through a duplication event more than 440 million years ago.
      All members of this small MDM2 gene family contain a single really interesting
      new gene (RING) domain (with the possible exception of lancelet MDM) which places
      them in the RING-domain superfamily. Similar to MDM2, the vast majority of
      proteins with RING domains are E3 ubiquitin ligases. Other RING domain E3
      ubiquitin ligases that target p53 are COP1, Pirh2, and MSL2. In this report, we
      present evidence that COP1, Pirh2, and MSL2 evolved independently of MDM2 and
      MDM4. We also show, through structure homology models of invertebrate MDM RING
      domains, that MDM2 is more evolutionarily conserved than MDM4.

PMID- 25372741
TI  - Transthyretin: a multifaceted protein.
AB  - Transthyretin is a highly conserved homotetrameric protein, mainly synthetized by
      the liver and the choroid plexus of brain. The carrier role of TTR is well-known;
      however, many other functions have emerged, namely in the nervous system.
      Behavior, cognition, neuropeptide amidation, neurogenesis, nerve regeneration,
      axonal growth and 14-3-3zeta metabolism are some of the processes where TTR has
      an important role. TTR aggregates are responsible for many amyloidosis such as
      familial amyloidotic polyneuropathy and cardiomyopathy. Normal TTR can also
      aggregate and deposit in the heart of old people and in preeclampsia placental
      tissue. Differences in TTR levels have been found in several neuropathologies,
      but its neuroprotective role, until now, was described in ischemia and
      Alzheimer's disease. The aim of this review is to stress the relevance of TTR,
      besides its well-known role on transport of thyroxine and retinol-binding
      protein.

PMID- 25372742
TI  - The importance of iron in the biosynthesis and assembly of [NiFe]-hydrogenases.
AB  - [NiFe]-hydrogenases (Hyd) are redox-active metalloenzymes that catalyze the
      reversible oxidation of molecular hydrogen to protons and electrons. These
      enzymes are frequently heterodimeric and have a unique bimetallic active site in
      their catalytic large subunit and possess a complement of iron sulfur (Fe-S)
      clusters for electron transfer in the small subunit. Depending on environmental
      and metabolic requirements, the Fe-S cluster relay shows considerable variation
      among the Hyd, even employing high potential [4Fe-3S] clusters for improved
      oxygen tolerance. The general iron sulfur cluster (Isc) machinery is required for
      small subunit maturation, possibly providing standard [4Fe-4S], which are then
      modified as required in situ. The [NiFe] cofactor in the active site also has an
      iron ion to which one CO and two CN- diatomic ligands are attached. Specific
      accessory proteins synthesize these ligands and insert the cofactor into the apo
      hydrogenase large subunit. Carbamoyl phosphate is the precursor of the CN-
      ligands, and recent experimental evidence suggests that endogenously generated
      CO2 might be one precursor of CO. Recent advances also indicate how the
      machineries responsible for cofactor generation obtain iron. Several transport
      systems for iron into bacterial cells exist; however, in Escherichia coli, it is
      mainly the ferrous iron transporter Feo and the ferric-citrate siderphore system
      Fec that are involved in delivering the metal for Hyd biosynthesis. Genetic
      analyses have provided evidence for the existence of key checkpoints during
      cofactor biosynthesis and enzyme assembly that ensure correct spatiotemporal
      maturation of these modular oxidoreductases.

PMID- 25372743
TI  - Seed evolution: parental conflicts in a multi-generational household.
AB  - Seeds are multi-generational structures containing a small embryonic plant
      enclosed in layers of diverse parental origins. The evolution of seeds was a
      pinnacle in an evolutionary trend towards a progressive retention of embryos and
      gametes within parental tissue. This strategy, which dates back to the first land
      plants, allowed an increased protection and nourishing of the developing embryo.
      Flowering plants took parental control one step further with the evolution of a
      biparental endosperm that derives from a second parallel fertilization event. The
      endosperm directly nourishes the developing embryo and allows not only the
      maternal genes, but also paternal genes, to play an active role during seed
      development. The appearance of an endosperm set the conditions for the
      manifestation of conflicts of interest between maternal and paternal genomes over
      the allocation of resources to the developing embryos. As a consequence, a
      dynamic balance was established between maternal and paternal gene dosage in the
      endosperm, and maintaining a correct balance became essential to ensure a correct
      seed development. This balance was achieved in part by changes in the genetic
      constitution of the endosperm and through epigenetic mechanisms that allow a
      differential expression of alleles depending on their parental origin. This
      review discusses the evolutionary steps that resulted in the appearance of seeds
      and endosperm, and the epigenetic and genetic mechanisms that allow a harmonious
      coinhabitance of multiple generations within a single seed.

PMID- 25372744
TI  - GM1 and GM2 gangliosides: recent developments.
AB  - GM1 and GM2 gangliosides are important components of the cell membrane and play
      an integral role in cell signaling and metabolism. In this conceptual overview,
      we discuss recent developments in our understanding of the basic biological
      functions of GM1 and GM2 and their involvement in several diseases. In addition
      to a well-established spectrum of disorders known as gangliosidoses, such as Tay
      Sachs disease, more and more evidence points at an involvement of GM1 in
      Alzheimer's and Parkinson's diseases. New emerging methodologies spanning from
      single-molecule imaging in vivo to simulations in silico have complemented
      standard studies based on ganglioside extraction.

PMID- 25372746
TI  - The structure, molecular interactions and bioactivities of proinsulin C-peptide
      correlate with a tripartite molecule.
AB  - Many biological roles have been assigned to proinsulin C-peptide over the years.
      Some appear surprisingly disparate and sometimes even contradictory, like
      chaperone-like actions and depository tendencies. This review summarizes recently
      reported biomolecular interactions of the peptide and presents how they correlate
      with structural and functional aspects into a partitioned molecular architecture.
      At the structural level, the C-peptide sequence and fold can be subdivided into
      three distinct parts ('tripartite'). At the functional level, its chaperone-like
      abilities, self-assembly, and membrane interactions, as well as interactions with
      relevant proteins can be separately ascribed to these three segments. At the
      biological level, the assignments are compatible with the suggested roles of C
      peptide in granular insulin storage, chaperone-like activities on insulin
      oligomers, possible depository tendencies, and proposed receptor interactions.
      Finally, the assignments give interesting parallels to further bioactive
      peptides, including glucagon and neurotensin. Provided pharmaceutical and
      clinical trials are successfully completed, the present interpretations should
      supply mechanistic explanations on C-peptide as a bioactive compound of
      importance in health and diabetes.

PMID- 25372747
TI  - The role of protein-derived free radicals as intermediaries of oxidative
      processes.
AB  - The fact that proteins are the main target of reactive species formed in the
      cells and extracellular fluids has led to the realization of a great deal of
      research devoted to revealing the molecular and biological consequences
      associated with the presence of intermediary protein radicals. This review
      article describes and comments upon the main chemical pathways involving primary
      proteic radicals.

PMID- 25372745
TI  - Epigenetic regulations through DNA methylation and hydroxymethylation: clues for
      early pregnancy in decidualization.
AB  - DNA methylation at cytosines is an important epigenetic modification that
      participates in gene expression regulation without changing the original DNA
      sequence. With the rapid progress of high-throughput sequencing techniques, whole
      genome distribution of methylated cytosines and their regulatory mechanism have
      been revealed gradually. This has allowed the uncovering of the critical roles
      played by DNA methylation in the maintenance of cell pluripotency, determination
      of cell fate during development, and in diverse diseases. Recently, rediscovery
      of 5-hydroxymethylcytosine, and other types of modification on DNA, have
      uncovered more dynamic aspects of cell methylome regulation. The interaction of
      DNA methylation and other epigenetic changes remodel the chromatin structure and
      determine the state of gene transcription, not only permanently, but also
      transiently under certain stimuli. The uterus is a reproductive organ that
      experiences dramatic hormone stimulated changes during the estrous cycle and
      pregnancy, and thus provides us with a unique model for studying the dynamic
      regulation of epigenetic modifications. In this article, we review the current
      findings on the roles of genomic DNA methylation and hydroxymethylation in the
      regulation of gene expression, and discuss the progress of studies for these
      epigenetic changes in the uterus during implantation and decidualization.

PMID- 25372748
TI  - Fliposomes: stimuli-triggered conformational flip of novel amphiphiles causes an
      instant cargo release from liposomes.
AB  - This review presents a new strategy for the design of stimuli-responsive
      liposomes for targeted delivery - the construction of a liposome membrane (lipid
      bilayer) using amphiphiles able to perform a stimuli-triggered conformational
      flip ('flipids'). When done simultaneously by a major or significant part of the
      bilayer molecules, this massive flip disrupts the liposome membrane and induces a
      rapid release of the liposome load specifically in response to the initial
      stimulus. The conformational switches incorporated into the amphiphilic molecules
      could potentially be controlled by various internal or external factors (pH,
      metal complexation, light, electric field, etc.). Using this concept, we designed
      a series of pH-triggerable flipids, and prepared and tested 'fliposomes' with
      extraordinary characteristics: high stability in storage and in serum combined
      with an instant release of their cargo in response to a weakly acidic medium.

PMID- 25372750
TI  - CXCL14 antagonizes the CXCL12-CXCR4 signaling axis.
AB  - CXCL12 and CXCL14 are evolutionarily conserved members of the CXC-type chemokine
      family. CXCL12 binds specifically to the G-protein-coupled receptor CXCR4 to
      induce the migration of primordial germ cells, hematopoietic stem cells, and
      inflammation-associated immune cells. In addition, CXCL12-CXCR4 signaling is
      often enhanced in malignant tumor cells and facilitates increased proliferation
      as well as metastasis. Although macrophage migration inhibitory factor and
      extracellular ubiquitin interact with CXCR4 as agonistic factors, CXCL12 was
      believed to be the sole chemokine ligand for CXCR4. However, a very recent report
      revealed that CXCL14 binds to CXCR4 with high affinity and efficiently inhibits
      CXCL12-mediated chemotaxis of hematopoietic progenitor and leukemia-derived
      cells. CXCL14 does not directly cross-compete with CXCL12 for the CXCR4 binding
      but instead inactivates CXCR4 via receptor internalization. Because both CXCL12
      and CXCL14 are expressed during embryogenesis and brain development in mice,
      these two chemokines could function in an interactive fashion. We propose that
      the CXCL14 gene has been conserved from fish to man due to its role in fine
      tuning the strength of CXCL12-mediated signal transduction. In addition to its
      biological implications, the above finding will be important for designing anti
      cancer compounds targeting the CXCL12-CXCR4 signaling axis. In fact, a stabilized
      dimeric peptide containing the C-terminal 51-77 amino acid residues of CXCL14 has
      been shown to have stronger CXCL12 antagonistic activity than full-length CXCL14.

PMID- 25372749
TI  - Endocytosis and the Src family of non-receptor tyrosine kinases.
AB  - The regulated intracellular transport of nutrient, adhesion, and growth factor
      receptors is crucial for maintaining cell and tissue homeostasis. Endocytosis, or
      endocytic membrane trafficking, involves the steps of intracellular transport
      that include, but are not limited to, internalization from the plasma membrane,
      sorting in early endosomes, transport to late endosomes/lysosomes followed by
      degradation, and/or recycling back to the plasma membrane through tubular
      recycling endosomes. In addition to regulating the localization of transmembrane
      receptor proteins, the endocytic pathway also controls the localization of non
      receptor molecules. The non-receptor tyrosine kinase c-Src (Src) and its closely
      related family members Yes and Fyn represent three proteins whose localization
      and signaling activities are tightly regulated by endocytic trafficking. Here, we
      provide a brief overview of endocytosis, Src function and its biochemical
      regulation. We will then concentrate on recent advances in understanding how Src
      intracellular localization is regulated and how its subcellular localization
      ultimately dictates downstream functioning. As Src kinases are hyperactive in
      many cancers, it is essential to decipher the spatiotemporal regulation of this
      important family of tyrosine kinases.

PMID- 25372751
TI  - Novel clathrin activity: developments in health and disease.
AB  - Clathrin self-assembles into a coat around vesicles filled with cargo such as
      nutrients, hormones, and proteins destined for degradation. Recent developments
      indicate clathrin is not a specialist, but is involved in different processes
      relevant to health and disease. Clathrin is used to strengthen centrosomes and
      mitotic spindles essential for chromosome segregation in cell division. In Wnt
      signaling, clathrin is a component of signalosomes on the plasma membrane needed
      to produce functional Wnt receptors. In glucose metabolism, a muscle-specific
      isoform, CHC22 clathrin, is key to the formation of storage compartments for
      GLUT4 receptor, and CHC22 dysfunction has been tied to type 2 diabetes. The
      activity of clathrin to self-assemble and to work with huntingtin-interacting
      proteins to organize actin is exploited by Listeria and enteropathic Escherichia
      coli in their infection pathways. Finally, there is an important connection
      between clathrin and human malignancies. Clathrin is argued to help transactivate
      tumor suppressor p53 that controls specific genes in DNA repair and apoptosis.
      However, this is debatable because trimeric clathrin must be made monomeric. To
      get insight on how the clathrin structure could be converted, the crystal
      structure of the trimerization domain is used in the development of the
      detrimerization switch hypothesis. This novel hypothesis will be relevant if
      connections continue to be found between CHC17 and p53 anti-cancer activity in
      the nucleus.

PMID- 25372752
TI  - Mammalian genome evolution as a result of epigenetic regulation of transposable
      elements.
AB  - Transposable elements (TEs) make up a large proportion of mammalian genomes and
      are a strong evolutionary force capable of rewiring regulatory networks and
      causing genome rearrangements. Additionally, there are many eukaryotic epigenetic
      defense mechanisms able to transcriptionally silence TEs. Furthermore, small RNA
      molecules that target TE DNA sequences often mediate these epigenetic defense
      mechanisms. As a result, epigenetic marks associated with TE silencing can be
      reestablished after epigenetic reprogramming - an event during the mammalian life
      cycle that results in widespread loss of parental epigenetic marks. Furthermore,
      targeted epigenetic marks associated with TE silencing may have an impact on
      nearby gene expression. Therefore, TEs may have driven species evolution via
      their ability to heritably alter the epigenetic regulation of gene expression in
      mammals.

PMID- 25372753
TI  - Neuroglobin - recent developments.
AB  - Neuroglobin (Ngb), a monomeric hexacoordinated heme protein of 17 kDa, was
      identified in 2000 in the nervous system. Accumulative evidence has proved that
      Ngb is an endogenous neuroprotective molecule against ischemic/hypoxic insults
      and oxidative stresses, and in most ischemic conditions, Ngb is up-regulated. The
      underlying mechanisms, however, are not fully clarified. Here we review the
      recent experimental findings, mainly focusing on the mechanisms of Ngb's
      protection and induction during ischemic/hypoxic conditions, the roles of Ngb in
      astrocytes and tumors, as well as Ngb's function in neurite outgrowth.

PMID- 25372754
TI  - The Jumonji family: past, present and future of histone demethylases in cancer.
AB  - The first Jumonji gene was cloned in 1995 by Takeuchi et al. [Takeuchi T,
      Yamazaki Y, Katoh-Fukui Y, Tsuchiya R, Kondo S, Motoyama J, Higashinakagawa T.
      Gene trap capture of a novel mouse gene, jumonji, required for neural tube
      formation. Genes Dev 1995; 9: 1211-22.]. Several genes sharing similar biological
      features have since been discovered, and are currently grouped into the JMJ
      family. Interestingly, their deregulation has been associated with cardiac
      disease, obesity, neurological disorders and cancer. One of the mechanisms
      underlying their function is gene expression modulation via histone post
      translational modifications (PTMs). Increasing evidence of Jumonji deregulation
      in tumours such as colon, prostate, haematological and breast cancer is
      continually emerging, hence the need to acquire a better understanding. The
      Genesapiens.org database of patient arrays allows target expression levels to be
      investigated in a wide range of cancers, corroborating and extending the role of
      the JMJ family. Here, we provide an overview of the expression profile and
      regulation of JMJ family members in cancer, examining the most recent literature
      in the light of analyses drawn from this database.

PMID- 25372755
TI  - Tachykinin: recent developments and novel roles in health and disease.
AB  - Over 80 years has passed since the discovery of substance P (SP), and a variety
      of peptides of the tachykinin (TK) family have been found and investigated. SP,
      neurokinin A (NKA), and neurokinin B (NKB) are representative peptides in
      mammalian species. SP and NKA are major excitatory neurotransmitters in the
      peripheral nervous system, while NKB is primarily involved in the central nervous
      system (CNS). Moreover, TK peptides play roles not only as neurotransmitters but
      also as local factors and are involved in almost all aspects of the regulation of
      physiological functions and pathophysiological processes. The role of SP as a
      mediator of pain processing and inflammation in peripheral tissues in
      coordination with transient receptor potential channels is well established,
      while novel aspects of TKs in relation to hematopoiesis, venous thromboembolism,
      tendinopathy, and taste perception have been clarified. In the CNS, the NKB
      signaling system in the hypothalamus has been shown to play a crucial role in the
      regulation of gonadotropin hormone secretion and the onset of puberty, and
      molecular biological studies have elucidated novel prophylaxic activities of TKs
      against neurogenic movement disorders based on their molecular structure. This
      review provides an overview of the novel aspects of TKs reported around the world
      in the last 5 years, with particular focus on nociception, inflammation,
      hemopoiesis, gonadotropin secretion, and CNS diseases.

PMID- 25372756
TI  - Circadian angiogenesis.
AB  - Daily rhythms of light/darkness, activity/rest and feeding/fasting are important
      in human physiology and their disruption (for example by frequent changes between
      day and night shifts) increases the risk of disease. Many of the diseases found
      to be associated with such disrupted circadian lifestyles, including cancer,
      cardiovascular diseases, metabolic disorders and neurological diseases, depend on
      pathological de-regulation of angiogenesis, suggesting that disrupting the
      circadian clock will impair the physiological regulation of angiogenesis leading
      to development and progression of these diseases. Today there is little known
      regarding circadian regulation of pathological angiogenesis but there is some
      evidence that supports both direct and indirect regulation of angiogenic factors
      by the cellular circadian clock machinery, as well as by circulating circadian
      factors, important for coordinating circadian rhythms in the organism. Through
      highlighting recent advances both in pre-clinical and clinical research on
      various diseases including cancer, cardiovascular disorders and obesity, we will
      here present an overview of the available knowledge on the importance of
      circadian regulation of angiogenesis and discuss how the circadian clock may
      provide alternative targets for pro- or anti-angiogenic therapy in the future.

PMID- 25372757
TI  - Transthyretin microheterogeneity and molecular interactions: implications for
      amyloid formation.
AB  - Aggregation of transthyretin (TTR), a plasma-binding protein for thyroxine and
      retinol-binding protein, is the cause of several amyloid diseases. Disease
      associated mutations are well known, but wild-type TTR is, to a lesser extent,
      also amyloidogenic. Monomerization, not oligomer formation as in several other
      depository diseases, is the rate-limiting step in TTR aggregation, and
      stabilization of the natively tetrameric form can inhibit amyloid formation.
      Modifications on Cys10, as well as interactions with native ligands in plasma,
      were early found to influence the equilibrium between tetrameric and monomeric
      TTR by dissociating or stabilizing the tetramer. Following these discoveries,
      synthetic ligands for pharmacological prevention of TTR aggregation could be
      developed. In this article, we outline how the different types of TTR
      interactions and its microheterogeneity in plasma are related to its propensity
      to form amyloid fibrils. We conclude that plasma constituents and dietary
      components may act as natural TTR stabilizers whose mechanisms of action provide
      cues for the amelioration of TTR amyloid disease.

PMID- 25372758
TI  - Epigenetic regulation of CC-chemokine ligand 2 in nonresolving inflammation.
AB  - Inflammation mediated by the crosstalk between leukocytes and resident tissue
      cells is crucial for the maintenance of homeostasis. Because chemokine ligands
      and receptors, which recruit a variety of leukocytes, are widely distributed
      among tissues, it is important to understand the mechanisms regulating
      inflammatory disease. Chemokines such as CC-chemokine ligand 2 (CCL2) amplify and
      maintain inflammation through chemokine-cytokine networks after the recruitment
      of circulating leukocytes. Chemokine-dependent nonresolving inflammation occurs
      in the peripheral and central nervous systems, and underlies several intractable
      diseases, including cancer and neuropathic pain. The chronic upregulation of
      chemokines is often mediated by epigenetic mechanisms consisting of DNA
      methylation, histone modification, and nucleosome positioning. In particular,
      histone acetylation and methylation have been shown to play important roles in
      the upregulation of chemokine expression. In addition to CCL2, several other
      chemokines strongly contribute to neuropathic pain through epigenetic induction.
      Consequently, targeting epigenetic changes may have therapeutic potential for
      nonresolving inflammatory diseases such as neuropathic pain. Further research
      into the epigenetics of inflammatory diseases should promote the development of
      novel and effective treatment strategies for intractable inflammatory diseases.

PMID- 25372760
TI  - Mechanisms of remyelination: recent insight from experimental models.
AB  - Oligodendrocytes and myelin play essential roles in the vertebrate central
      nervous system. Demyelination disrupts saltatory nerve conduction, leading to
      axonal degeneration and neurological disabilities. Remyelination is a
      regenerative process that replaces lost myelin. However, remyelination is
      disrupted in demyelinating diseases such as multiple sclerosis, at least
      partially, due to the failure of oligodendrocyte precursor cells to differentiate
      into myelinating oligodendrocytes. Understanding the molecular and cellular
      mechanisms that impact the differentiation of oligodendrocytes and myelination
      may help in the development of novel therapeutic strategies for demyelinating
      diseases. In this review, we focus on the molecular mechanisms controlling the
      differentiation of oligodendrocytes during remyelination, and we discuss the
      function of astrocytes and microglia in animal models of demyelinating diseases.

PMID- 25372761
TI  - Alcohol oxidation by flavoenzymes.
AB  - This review article describes the occurrence, general properties, and substrate
      specificity of the flavoenzymes belonging to the glucose-methanol-choline
      oxidoreductase superfamily and the l-alpha-hydroxyacid dehydrogenase family. Most
      of these enzymes catalyze the oxidations of hydroxyl groups, yielding carbonyl
      moieties. Over the years, carbanion, hydride transfer, and radical mechanisms
      have been discussed for these enzymes, and the main experimental evidences
      supporting these mechanisms are presented here. Regardless of the chemical nature
      of the organic substrate (i.e., activated and non-activated alcohols), a hydride
      transfer mechanism appears to be the most plausible for the flavoenzymes acting
      on CH-OH groups. The reaction of most of these enzymes likely starts with proton
      abstraction from the substrate hydroxyl group by a conserved active site
      histidine. Among the different approaches carried out to determine the chemical
      mechanisms with physiological substrates, primary substrate and solvent deuterium
      kinetic isotope effect studies have provided the most unambiguous evidences. It
      is expected that the numerous studies reported for these enzymes over the years
      will be instrumental in devising efficient industrial biocatalysts and drugs.

PMID- 25372759
TI  - Update on non-canonical microRNAs.
AB  - Non-canonical microRNAs are a recently-discovered subset of microRNAs. They
      structurally and functionally resemble canonical miRNAs, but were found to follow
      distinct maturation pathways, typically bypassing one or more steps of the
      classic canonical biogenesis pathway. Non-canonical miRNAs were found to have
      diverse origins, including introns, snoRNAs, endogenous shRNAs and tRNAs. Our
      knowledge about their functions remains relatively primitive; however, many
      interesting discoveries have taken place in the past few years. They have been
      found to take part in several cellular processes, such as immune response and
      stem cell proliferation. Adversely, their deregulation has pathologic effects on
      several different tissues, which strongly suggests an integral role for non
      canonical miRNAs in disease pathogenesis. In this review, we discuss the recently
      discovered functional characteristics of non-canonical miRNAs and illustrate
      their principal maturation pathways as well as debating their potential role in
      multiple cellular processes.

PMID- 25372762
TI  - Podocytes: recent biomolecular developments.
AB  - Podocytes are postmitotic renal glomerular cells with multiple ramifications that
      extend from the cell body. Processes departing from a podocyte interdigitate with
      corresponding projections from neighboring cells and form an intricate web that
      enwraps the glomerular capillary completely. Podocyte processes are
      interconnected by the slit diaphragm, an adhesion junction mostly formed by Ig
      like molecules, cadherins/protocadherins, ephrin/eph, and neurexin molecules
      organized in an assembly that resembles synaptic junctions. Podocyte failure is
      primarily or secondarily implicated in all forms of proteinuric glomerular
      diseases, as confirmed by the morphological changes of their elaborate cell
      architecture detectable by electron microscopy. Importantly, mutations of
      podocyte proteins are responsible for the most severe forms of congenital
      nephrotic syndrome. In the last 15 years, progressive technological advances have
      aided the study of podocyte biology and pathology, confirming the relevance of
      podocyte molecules and signaling pathways for the function of the glomerular
      filter. This review will examine the most important and newest discoveries in the
      field, which is rapidly evolving, hopefully leading to a detailed knowledge of
      this fascinating cell and to the development of specific therapeutic options for
      proteinuric diseases.

PMID- 25372763
TI  - Regulation of meiotic entry and gonadal sex differentiation in the human: normal
      and disrupted signaling.
AB  - Meiosis is a unique type of cell division that is performed only by germ cells to
      form haploid gametes. The switch from mitosis to meiosis exhibits a distinct sex
      specific difference in timing, with female germ cells entering meiosis during
      fetal development and male germ cells at puberty when spermatogenesis is
      initiated. During early fetal development, bipotential primordial germ cells
      migrate to the forming gonad where they remain sexually indifferent until the sex
      specific differentiation of germ cells is initiated by cues from the somatic
      cells. This irreversible step in gonadal sex differentiation involves the
      initiation of meiosis in fetal ovaries and prevention of meiosis in the germ
      cells of fetal testes. During the last decade, major advances in the
      understanding of meiosis regulation have been accomplished, with the discovery of
      retinoic acid as an inducer of meiosis being the most prominent finding.
      Knowledge about the molecular mechanisms regulating meiosis signaling has mainly
      been established by studies in rodents, while this has not yet been extensively
      investigated in humans. In this review, the current knowledge about the
      regulation of meiosis signaling is summarized and placed in the context of fetal
      gonad development and germ cell differentiation, with emphasis on results
      obtained in humans. Furthermore, the consequences of dysregulated meiosis
      signaling in humans are briefly discussed in the context of selected pathologies,
      including testicular germ cell cancer and some forms of male infertility.

PMID- 25372764
TI  - Developmental evolution and the origins of phenotypic variation.
AB  - Because of the variability of relevant developmental resources across different
      environments, and because only a portion of the genome is expressed in any
      individual organism as a result of its specific developmental context and
      experience, what is actually realized during the course of individual development
      represents only one of many possibilities. One conclusion to be drawn from this
      insight is that the origin of phenotypic traits and their variation can be traced
      to the process of development. In this conceptual overview, I briefly explore how
      recent efforts to integrate genetic, epigenetic, and environmental levels of
      analysis through a developmental lens is advancing our understanding of the
      generation of the stability and variability of phenotypic outcomes observed
      within and across generations. A growing body of evidence indicates that
      phenotypes are the outcomes of the whole developmental system, comprised of the
      organism, with its particular genetic and cellular make-up in its specific
      physical, biological, and social environments. I conclude that the emergent
      products of development are epigenetic, not just genetic, and evolutionary
      explanation cannot be complete without a developmental mode of analysis.

PMID- 25372765
TI  - Symposium.

PMID- 25372766
TI  - Influence of gold additives on the stability and phase transformation of titanate
      nanostructures.
AB  - Gold nanoparticles were prepared and characterized on protonated (H-form)
      titanate nanotubes (TiONTs) and nanowires (TiONWs). The chemical nature and
      morphology of gold particles were monitored by X-ray photoelectron spectroscopy
      (XPS), Raman spectroscopy, X-ray diffraction (XRD) and high resolution electron
      microscopy (HRTEM). The optical properties of Au-containing titanate nanowires
      were explored by means of ultraviolet-visible diffuse reflectance spectroscopy.
      The size distribution and homogeneity of gold particles depend on the reduction
      mode from the corresponding gold salt to metal particles. Smaller clusters (3-8
      nm) were obtained with the NaBH4 reactant at 293 K than with molecular hydrogen
      reduction. An unexpectedly high binding energy gold state was found by XPS in
      gold-loaded titanate nanostructures. This state was absent from the spectra of
      gold-loaded TiO2(110). A likely explanation for this phenomenon, supported also
      by the characteristic decrease of band gap energy from 3.10 eV to 2.74 eV with
      increasing Au content, is that depending on the metal loading and titanate
      structure, Au is stabilized on titanate nanowires partially in positively charged
      gold form by ion exchange and also as Au clusters. Our important new finding is
      that the thermal annealing behavior of Au-loaded titanate nanotubes and nanowires
      is different. The former lose their tubular morphology and are readily
      transformed into anatase even at a very low temperature of 473 K. On the other
      hand, gold stabilizes the layered structure of titanate nanowires up to 873 K. 

PMID- 25372767
TI  - Measuring the Quality of Care in Different Settings.
AB  - As HCFA initiates the next generation of health plan performance measures, the
      agency must address challenges associated with measuring the quality of care in
      all of the settings in which Medicare and Medicaid beneficiaries obtain care. One
      such challenge will be to integrate health plan performance measurement and
      health care quality measurement initiatives, which have been proceeding
      separately. Of equal importance is the challenge to improve coordination across
      the diverse, setting-specific quality measurement initiatives now in various
      stages of development or implementation by HCFA. Finally, HCFA must address the
      challenge of improving the collection, reporting, and analysis of data needed for
      health care quality measurement. This article describes these challenges and
      suggests steps HCFA might take in addressing them.

PMID- 25372768
TI  - Medicare's End Stage Renal Disease Program.
AB  - Perhaps no other Federal Government program can lay claim to have saved as many
      lives as the Medicare end stage renal disease (ESRD) program. Since its inception
      in 1973, as a result of the Social Security Amendments of 1972 (Public Law 92
      603, section 299I), over 1 million persons have received life-saving renal
      replacement therapy under this program. Prior to the enactment of this
      legislation, treatment was limited to a very few patients due to its extremely
      high cost and the limited number of dialysis machines. In the 1960s, it was not
      uncommon for hospitals that had dialysis machines to appoint special committees
      to review applicants for dialysis and decide who should receive treatment, the
      others were left to die of renal failure. Public Law 92-603 removed this odious
      task from the nephrology community. A person with ESRD is entitled to Medicare if
      he/she is fully or currently insured for benefits under Social Security, or is a
      spouse or dependent of an insured person. Consequently, entitlement is less than
      universal, with 92 percent of all persons with ESRD qualifying for Medicare
      coverage.

PMID- 25372769
TI  - Citric acid-based hydroxyapatite composite scaffolds enhance calvarial
      regeneration.
AB  - Citric acid-based polymer/hydroxyapatite composites (CABP-HAs) are a novel class
      of biomimetic composites that have recently attracted significant attention in
      tissue engineering. The objective of this study was to compare the efficacy of
      using two different CABP-HAs, poly (1,8-octanediol citrate)-click-HA (POC-Click
      HA) and crosslinked urethane-doped polyester-HA (CUPE-HA) as an alternative to
      autologous tissue grafts in the repair of skeletal defects. CABP-HA disc-shaped
      scaffolds (65 wt.-% HA with 70% porosity) were used as bare implants without the
      addition of growth factors or cells to renovate 4 mm diameter rat calvarial
      defects (n = 72, n = 18 per group). Defects were either left empty (negative
      control group), or treated with CUPE-HA scaffolds, POC-Click-HA scaffolds, or
      autologous bone grafts (AB group). Radiological and histological data showed a
      significant enhancement of osteogenesis in defects treated with CUPE-HA scaffolds
      when compared to POC-Click-HA scaffolds. Both, POC-Click-HA and CUPE-HA
      scaffolds, resulted in enhanced bone mineral density, trabecular thickness, and
      angiogenesis when compared to the control groups at 1, 3, and 6 months post
      trauma. These results show the potential of CABP-HA bare implants as
      biocompatible, osteogenic, and off-shelf-available options in the repair of
      orthopedic defects.

PMID- 25372770
TI  - How can we get close to zero? The potential contribution of biomedical prevention
      and the investment framework towards an effective response to HIV.
AB  - BACKGROUND: In 2011 an Investment Framework was proposed that described how the
      scale-up of key HIV interventions could dramatically reduce new HIV infections
      and deaths in low and middle income countries by 2015. This framework included
      ambitious coverage goals for prevention and treatment services resulting in a
      reduction of new HIV infections by more than half. However, it also estimated a
      leveling in the number of new infections at about 1 million annually after 2015.
      METHODS: We modeled how the response to AIDS can be further expanded by scaling
      up antiretroviral treatment (ART) within the framework provided by the 2013 WHO
      treatment guidelines. We further explored the potential contributions of new
      prevention technologies: 'Test and Treat', pre-exposure prophylaxis and an HIV
      vaccine. FINDINGS: Immediate aggressive scale up of existing approaches including
      the 2013 WHO guidelines could reduce new infections by 80%. A 'Test and Treat'
      approach could further reduce new infections. This could be further enhanced by a
      future highly effective pre-exposure prophylaxis and an HIV vaccine, so that a
      combination of all four approaches could reduce new infections to as low as
      80,000 per year by 2050 and annual AIDS deaths to 260,000. INTERPRETATION: In a
      set of ambitious scenarios, we find that immediate implementation of the 2013 WHO
      antiretroviral therapy guidelines could reduce new HIV infections by 80%. Further
      reductions may be achieved by moving to a 'Test and Treat' approach, and
      eventually by adding a highly effective pre-exposure prophylaxis and an HIV
      vaccine, if they become available.

PMID- 25372772
TI  - State Implementation of the AIDS Drug Assistance Programs.
AB  - Acquired immunodeficiency syndrome (AIDS) drug assistance programs (ADAPs)
      provide access to medications for people who lack other health coverage. In this
      article, the authors present the results of a 1997 survey identifying how 48
      States implemented ADAPs, focusing on the number of beneficiaries, medical and
      financial eligibility criteria, the administration of waiting lists, and the
      coverage of drugs including protease inhibitors. Increased funding for ADAPs is
      necessary to maintain this important part of the public sector safety net for
      human immunodeficiency virus (HIV) care.

PMID- 25372771
TI  - Acid-base transport in pancreatic cancer: molecular mechanisms and clinical
      potential.
AB  - Solid tumors are characterized by a microenvironment that is highly acidic, while
      intracellular pH (pHi) is normal or even elevated. This is the result of elevated
      metabolic rates in the highly proliferative cancer cells, in conjunction with
      often greatly increased rates of net cellular acid extrusion. Studies in various
      cancers have suggested that while the acid extrusion mechanisms employed are
      generally the same as those in healthy cells, the specific transporters
      upregulated vary with the cancer type. The main such transporters include
      Na(+)/H(+) exchangers, various HCO3(-) transporters, H(+) pumps, and lactate-H(+)
      cotransporters. The mechanisms leading to their dysregulation in cancer are
      incompletely understood but include changes in transporter expression levels,
      trafficking and membrane localization, and posttranslational modifications. In
      turn, accumulating evidence has revealed that in addition to supporting their
      elevated metabolic rate, their increased acid efflux capacity endows the cancer
      cells with increased capacity for invasiveness, proliferation, and chemotherapy
      resistance. The pancreatic duct exhibits an enormous capacity for acid-base
      transport, rendering pHi dysregulation a potentially very important topic in
      pancreatic ductal adenocarcinoma (PDAC). PDAC - accounting for about 90% of all
      pancreatic cancers - has one of the highest cancer mortality rates known, and new
      diagnostic and treatment options are highly needed. However, very little is known
      about whether pH regulation is altered in PDAC and, if so, the possible role of
      this in cancer development. Here, we review current models for pancreatic acid
      base transport and pH homeostasis and summarize current views on acid-base
      dysregulation in cancer, focusing where possible on the few studies to date in
      PDAC. Finally, we present new data-mining analyses of acid-base transporter
      expression changes in PDAC and discuss essential directions for future work. 

PMID- 25372773
TI  - Assessing Medicare Health Plan Performance in Serving Beneficiary Subpopulations.
AB  - In this analysis, the authors examined differences in managed care health plan
      performance ratings between selected subgroups of the Medicare population who may
      have exceptional health care needs (EHCNs) or may require special plan efforts to
      facilitate effective service use compared with the residual enrolled population.
      Findings indicated that disabled enrollees have lower plan ratings across all
      dimensions of performance than do other enrollees. Aged enrollees in self
      reported fair/poor health and those with limited independence have lower ratings
      for most dimensions of performance. Finally, although Hispanic persons and
      persons other than white were more satisfied with their health plans, overall,
      they had lower ratings for dimensions of the process of care and access to
      services.

PMID- 25372774
TI  - Favorable effects of vitamin D supplementation on pregnancy outcomes in
      gestational diabetes: a double blind randomized controlled clinical trial.
AB  - Gestational diabetes mellitus (GDM) has been recognized as a significant risk
      factor for unfavorable pregnancy outcomes. Prevalence of vitamin D deficiency is
      highly prevalent among women with GDM. This study was designed to assess the
      effect of vitamin D supplementation on pregnancy outcomes of pregnant women with
      GDM who were not on oral hypoglycemic agents. This randomized controlled clinical
      trial was performed among 45 pregnant women diagnosed with GDM at 24-28 weeks'
      gestation. Subjects were randomly assigned to consume either vitamin D
      supplements (cholecalciferol) or placebo. Individuals in the vitamin D group
      (n=22) received 50 000 IU vitamin D3 pearl 2 times during the study: at study
      baseline and day 21 of intervention and those in placebo group (n=23) received 2
      placebos at the mentioned times. Fasting blood samples were taken at baseline to
      measure fasting plasma glucose. Participants underwent a 3-h oral glucose
      tolerance tests (OGTT) and the blood samples were collected at time 60, 120, and
      180 min to measure plasma glucose levels. Newborn's weight, height, head
      circumference, Apgar score, and hyperbilirubinemia were determined. Taking
      vitamin D supplements, compared with placebo, resulted in improved pregnancy
      outcomes; such that those in the vitamin D group had no case of polyhydramnios,
      while 17.4% of subjects in placebo group had this condition (p=0.04). In
      addition, newborn's hyperbilirubinemia was significantly lower in vitamin D group
      than that in placebo group (27.3% vs. 60.9%, p=0.02). In conclusion, vitamin D
      supplementation for 6 weeks among pregnant women with GDM resulted in decreased
      maternal polyhydramnios and infant hyperbilirubinemia compared with placebo.
      Clinical trial registration number www.irct.ir:IRCT201305115623N7. 

PMID- 25372775
TI  - High thyroid-stimulating hormone level is associated with the risk of developing
      atherosclerosis in subclinical hypothyroidism.
AB  - The aim of our study was to assess the potential role of thyroid-stimulating
      hormone (TSH) in the risk of developing atherosclerosis in subclinical
      hypothyroidism (SCH). A cohort of 240 SCH patients and 150 euthyroid volunteers
      were recruited for the study. SCH patients were stratified into 2 groups
      according to TSH levels (group A: TSH<10 mIU/l; group B: TSH>10 mIU/l). All
      subjects were examined for clinical and biochemical parameters. Visfatin, omentin
      1, and circulating endothelial biomarkers were measured. Patients in group B
      received l-thyroxine replacement to achieve euthyroidism; after 6 months of
      euthyroidism all measurements were repeated. Patients with SCH had higher total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and C-reactive
      protein (CRP) levels and lower nitric oxide (NO) and omentin-1 levels compared to
      euthyroid subjects (all p<0.05). TC, LDL-C, and CRP decreased significantly,
      while NO and omentin-1 levels increased significantly after l-thyroxine
      replacement. Based on multivariate liner stepwise regression analysis, omentin-1
      was independently correlated with BMI and TSH; NO was independently correlated
      with age, TSH, LDL-C, and omentin-1. High TSH level contributes to endothelial
      dysfunction in SCH, while TSH-induced decrease of omentin-1 provides a new link
      between SCH and atherogenic risk.

PMID- 25372776
TI  - The relative merits of cord blood as a cell source for autologous T regulatory
      cell therapy in type 1 diabetes.
AB  - Cord blood has been used as a cell source for therapeutic purposes in children
      with type 1 diabetes and other disorders. Here, we explore the benefits of cord
      blood as an autologous source of T regulatory cells for immune cell therapy in
      patients. CD4(+)CD25(+) T regulatory cells were isolated from cord blood and
      adult peripheral blood of healthy donors and compared during and after expansion
      in a 14-day protocol incorporating anti-CD3/anti-CD28 beads, and IL-2 with or
      without rapamycin. Cord blood T regulatory cells were largely naive (89+/-7 vs.
      31+/-10% in young adults, p<0.0001), and had higher expansion yields (median
      5,968-fold) than adult T regulatory cells (median 516-fold, p=0.001) and adult
      naive T regulatory cells (median 820-fold, p=0.003). Rapamycin reduced expansion
      yields, but was not necessary to obtain pure expanded cord blood T regulatory
      cells as judged by FOXP3 staining (94+/-3%), methylation status of FOXP3 (97%),
      and intracellular effector cytokine staining (< 6%). Expanded adult T regulatory
      cells were much less pure in the absence of rapamycin (72+/-19% FOXP3; 76% by
      methylation status, <13% INF-gamma, <16% IL-4, <5% IL-17 positive), but purity
      was achieved by inclusion of rapamycin during expansion. Despite differences in
      purity, all preparations of expanded T regulatory from all sources were able to
      strongly suppress proliferation of T effector cells in vitro. Our findings
      suggest that cord blood is an excellent source of T regulatory cells for
      expansion and autologous cell therapy that may be considered as a strategy to
      prevent immune-mediated destruction of beta cells in type 1 diabetes.

PMID- 25372777
TI  - Expression of the cAMP binding protein EPAC1 in thyroid tumors and growth
      regulation of thyroid cells and thyroid carcinoma cells by EPAC proteins.
AB  - The thyrotropin receptor-cAMP pathway is central in growth regulation of thyroid
      cells and thyroid tumorigenesis, and it regulates expression of thyroid specific
      genes. Recently, 2 new protein kinase A-independent cAMP effectors named EPAC1
      and 2 were described that activate additional intracellular pathways. The aim of
      our study was to investigate the role of EPAC proteins in growth regulation of
      thyroid cells and thyroid carcinomas. EPAC1 expression was investigated
      immunohistochemically in tissues of various thyroid tumors. Utilizing MTT assay,
      the effect of EPAC stimulation on proliferation in thyroid carcinoma cells and in
      non-transformed rat FRTL5 cells was investigated. The activation of intracellular
      signaling pathways was examined by RAP pull-down assay and Western blots. EPAC1
      expression was strong in non-oxyphilic follicular thyroid adenomas and carcinomas
      and in follicular papillary thyroid carcinomas. It was moderate in oxyphilic
      follicular tumors and classical and tall cell papillary carcinomas. In contrast,
      EPAC1 expression was low in poorly differentiated carcinomas and very low in
      anaplastic carcinomas. Thyroid carcinoma cell lines showed no or very weak EPAC1
      expression and exhibited no growth-promoting effect after EPAC stimulation. Non
      transformed rat FRTL5 cells were growth-stimulated by an EPAC-specific cAMP
      analogue and showed EPAC-dependent activation of RAP, ERK, and p70S6 kinase.
      EPAC1 expression and cellular response to EPAC activation in rat FRTL5 cells
      reflect cellular responses to cAMP and TSH stimulation in non-transformed thyroid
      cells. In undifferentiated thyroid carcinomas, loss of EPAC1 expression may be in
      accordance with the loss of thyroid-specific functions and the loss of
      responsiveness of the TSHR-cAMP pathway. 

PMID- 25372778
TI  - Maternal prolactin inhibition causes changes in leptin at 22- and 30-day-old
      pups.
AB  - Breastfeeding is associated with obesity prevention. We showed previously that
      prolactin inhibition at the end of lactation causes hyperleptinemia at weaning
      (PN21) and programs for obesity, insulin resistance, dyslipidemia, and leptin
      resistance (PN180). Here, we evaluate the source of neonatal hyperleptinemia and
      how it develops during the nutritional transition from milk through solid food.
      Lactating rats were treated with bromocriptine (BRO), a prolactin inhibitor, 0.5
      mg twice a day, or saline (CON) for the last 3 days of lactation. All parameters
      were studied at PN22 and PN30. At PN22, BRO-treated rats showed lower food
      intake, body mass, and body length. At PN30, only body length and mesenteric fat
      mass were lower. Despite normal plasma leptin levels at PN22, the adipose tissue
      leptin mRNA expression was lower, while plasma leptin was higher in PN30,
      possibly due to a higher adipose mesenteric tissue production. At PN22, the
      hypothalamus seems to be more sensitive to leptin, since OBR and STAT3 are
      higher. Conversely, at PN30 leptin signaling pathway is suggestive of leptin
      resistance with lower STAT3 and higher SOCS3 in hypothalamus and consequently
      higher NPY. Glycemia was lower at PN22 and higher at PN30, without changes in
      plasma insulin levels. At PN30, BRO-treated rats had other metabolic changes such
      as higher plasma cholesterol, lower HDL-c, higher hepatic cholesterol and AST,
      suggesting a liver dysfunction. Our data show that milk supply can exert a
      crucial role in the imprinting of a second leptin peak, which is important for
      survival adaptation to adverse nutritional conditions. 

PMID- 25372779
TI  - 3-Iodothyronamine-mediated metabolic suppression increases the phosphorylation of
      AMPK and induces fuel choice toward lipid mobilization.
AB  - Despite broad medical application, induction of artificial hypometabolism in
      vitro and its biochemical consequence have been rarely addressed. This study
      aimed to elucidate whether 3-iodothyronamine (T1AM) induces hypometabolism in an
      in vitro model with activation of AMP-activated protein kinase (AMPK) and whether
      it leads to a switch in primary fuel from carbohydrates to lipids as observed in
      in vivo models. Mouse C2C12 myotube and T1AM, a natural derivative of thyroid
      hormone, were used in this study. The oxygen consumption rate (OCR) decreased in
      a dose-dependent manner in response to 0-100 MUM T1AM for up to 10 h. Upon 6-h of
      exposure to 75 MUM T1AM, the OCR was reduced to 60 vs. ~ 95% for the control. The
      intracellular [AMP]/[ATP] was 1.35-fold higher in T1AM-treated cells. RT-PCR and
      immunoblotting analyses revealed that treated cells had upregulated p-AMPK/AMPK
      (1.8-fold), carnitine palmitoyl transferase 1 mRNA, and pyruvate dehydrogenase
      kinase, and downregulated acetyl CoA carboxylase (0.4-fold) and pyruvate
      dehydrogenase phosphatase. The treated cells had darker periodic acid-Schiff
      staining with 1.2-fold greater glycogen content than controls. Taken together,
      the hypometabolic response of myotubes to T1AM was dramatic and accompanied by
      increases in both the relative abundance of AMP and AMPK activation, and fuel
      choice favoring lipids over carbohydrates. These results are consistent with the
      general trends observed for rodent models and true hibernators. 

PMID- 25372780
TI  - Modification of human islet preparation: an effective approach to improve graft
      outcome after islet transplantation?
AB  - Revascularisation of transplanted islets is an essential prerequisite for graft
      survival and function. However, current islet isolation procedures deprive the
      islets of endothelial tubulets. This may have a detrimental effect on the
      revascularisation process of islets following transplantation. We hypothesise
      that modification of the isolation procedure that preserves islet endothelial
      vessels may improve the islet revascularisation process following
      transplantation. Here, we present a modified islet isolation method by which a
      substantial amount of endothelial cells still attached to the islets could be
      preserved. The islets with preserved endothelial cells isolated by this method
      were revascularised within 3 days, not observed in islets isolated by standard
      methods. Further, we observed that grafts of islets isolated by standard methods
      had more patches of dead tissue than islet grafts obtained by the modified
      method, indicating that attached endothelial cells may play an important role in
      the islet revascularisation process and potentially help to improve the
      transplantation outcome. 

PMID- 25372781
TI  - Preventive Services for Children Under Medicaid, 1989 and 1992.
AB  - Receipt of key preventive services among Medicaid children in four States is
      examined. Between 1989 and 1992, small-to-moderate improvements in well-child
      visit and immunization rates were observed. Age, eligibility group, and statewide
      factors affected these rates. Uniformly low use of preventive dental care was
      found. These rates were generally higher among children with well-child visits.
      To understand the full extent of preventive care for children, all Medicaid
      financed well-child services should be considered, not just those provided under
      the Early and Periodic Screening, Diagnostic, and Treatment (EPSDT) services
      program. Nonetheless, EPSDT is a critical vehicle for outreach and case
      management.

PMID- 25372782
TI  - N-capping motifs promote interaction of amphipathic helical peptides with
      hydrophobic surfaces and drastically alter hydrophobicity values of individual
      amino acids.
AB  - Capping rules, which govern interactions of helical peptides with hydrophobic
      surfaces, were never established before due to lack of methods for the direct
      measurement of polypeptide structure on the interphase boundary. We employed
      proteomic techniques and peptide retention modeling in reversed-phase
      chromatography to generate a data set sufficient for amino acid population
      analysis at helix ends. We found that interactions of amphipathic helical
      peptides with a hydrophobic C18 phase are induced by a unique motif featuring
      hydrophobic residues in the N1 and N2 positions adjacent to the N-cap (Asn, Asp,
      Ser, Thr, Gly), followed by Glu, Gln, or Asp in position N3 to complete a capping
      box. A favorable N-capping arrangement prior to amphipathic helix may result in
      the highest hydrophobicity (retention on C18 columns) of Asp/Asn (or Glu/Gln)
      peptide analogues among all naturally occurring amino acids when placed in N-cap
      or N3 position, respectively. These results contradict all previously reported
      hydrophobicity scales and provide new insights into our understanding of the
      phenomenon of hydrophobic interactions. 

PMID- 25372783
TI  - Overview of the Medicare and Medicaid Programs.

PMID- 25372784
TI  - Automated detection framework of the calcified plaque with acoustic shadowing in
      IVUS images.
AB  - Intravascular Ultrasound (IVUS) is one ultrasonic imaging technology to acquire
      vascular cross-sectional images for the visualization of the inner vessel
      structure. This technique has been widely used for the diagnosis and treatment of
      coronary artery diseases. The detection of the calcified plaque with acoustic
      shadowing in IVUS images plays a vital role in the quantitative analysis of
      atheromatous plaques. The conventional method of the calcium detection is manual
      drawing by the doctors. However, it is very time-consuming, and with high inter
      observer and intra-observer variability between different doctors. Therefore, the
      computer-aided detection of the calcified plaque is highly desired. In this
      paper, an automated method is proposed to detect the calcified plaque with
      acoustic shadowing in IVUS images by the Rayleigh mixture model, the Markov
      random field, the graph searching method and the prior knowledge about the
      calcified plaque. The performance of our method was evaluated over 996 in-vivo
      IVUS images acquired from eight patients, and the detected calcified plaques are
      compared with manually detected calcified plaques by one cardiology doctor. The
      experimental results are quantitatively analyzed separately by three evaluation
      methods, the test of the sensitivity and specificity, the linear regression and
      the Bland-Altman analysis. The first method is used to evaluate the ability to
      distinguish between IVUS images with and without the calcified plaque, and the
      latter two methods can respectively measure the correlation and the agreement
      between our results and manual drawing results for locating the calcified plaque
      in the IVUS image. High sensitivity (94.68%) and specificity (95.82%), good
      correlation and agreement (>96.82% results fall within the 95% confidence
      interval in the Student t-test) demonstrate the effectiveness of the proposed
      method in the detection of the calcified plaque with acoustic shadowing in IVUS
      images. 

PMID- 25372785
TI  - Multimodal retinal vessel analysis in CADASIL patients.
AB  - PURPOSE: To further elucidate retinal findings and retinal vessel changes in
      Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) patients by means of high resolution retinal
      imaging. METHODS: 28 eyes of fourteen CADASIL patients and an equal number of
      control subjects underwent confocal scanning laser ophthalmoscopy (cSLO),
      spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer
      (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel
      measurement techniques were applied: RNFL thickness, a semiautomatic software
      tool based on cSLO images and manual vessel outlining based on SD-OCT. RESULTS:
      Mean age of patients was 56.2 +/- 11.6 years. Arteriovenous nicking was present
      in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and
      choroidal volume were 8.77 +/- 0.46 mm(3) and 8.83 +/- 2.24 mm(3). RNFL
      measurements showed a global increase of 105.2 um ( CONTROL GROUP: 98.4 um; p =
      0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries
      and veins were 102.5 um (106.0 um; p = 0.21) and 128.6 um (124.4 um; p = 0.27)
      respectively. Manual SD-OCT measurements revealed significantly increased mean
      arterial 138.7 um (125.4 um; p<0.001) and venous 160.0 um (146.9; p = 0.003)
      outer diameters as well as mean arterial 27.4 um (19.2 um; p<0.001) and venous
      18.3 um (15.7 um; p<0.001) wall thicknesses in CADASIL patients. CONCLUSIONS: The
      findings reflect current knowledge on pathophysiologic changes in vessel
      morphology in CADASIL patients. SD-OCT may serve as a complementary tool to
      diagnose and follow-up patients suffering from cerebral small-vessel diseases.

PMID- 25372786
TI  - Smoking Among Medicaid Insured Mothers: What are the Neonatal Expenses?
AB  - Approximately 13 percent of all pregnant women smoke during pregnancy despite
      known adverse health effects. Medicaid Programs pay for an estimated 27-53
      percent of all births, yet little is known about smoking prevalence nor resulting
      expenses in this population. Findings indicate that pregnant women with
      deliveries paid by Medicaid are more than twice as likely to smoke as privately
      insured women; two-thirds of the estimated $366 million in 1996 neonatal expenses
      attributable to maternal smoking accrues to Medicaid Programs and these estimates
      vary widely across States. In light of these estimates, States should carefully
      consider targeted interventions and appropriate policies.

PMID- 25372787
TI  - Patterns and potential drivers of dramatic changes in Tibetan lakes, 1972-2010.
AB  - Most glaciers in the Himalayas and the Tibetan Plateau are retreating, and
      glacier melt has been emphasized as the dominant driver for recent lake
      expansions on the Tibetan Plateau. By investigating detailed changes in lake
      extents and levels across the Tibetan Plateau from Landsat/ICESat data, we found
      a pattern of dramatic lake changes from 1970 to 2010 (especially after 2000) with
      a southwest-northeast transition from shrinking, to stable, to rapidly expanding.
      This pattern is in distinct contrast to the spatial characteristics of glacier
      retreat, suggesting limited influence of glacier melt on lake dynamics. The
      plateau-wide pattern of lake change is related to precipitation variation and
      consistent with the pattern of permafrost degradation induced by rising
      temperature. More than 79% of lakes we observed on the central-northern plateau
      (with continuous permafrost) are rapidly expanding, even without glacial
      contributions, while lakes fed by retreating glaciers in southern regions (with
      isolated permafrost) are relatively stable or shrinking. Our study shows the
      limited role of glacier melt and highlights the potentially important
      contribution of permafrost degradation in predicting future water availability in
      this region, where understanding these processes is of critical importance to
      drinking water, agriculture, and hydropower supply of densely populated areas in
      South and East Asia. 

PMID- 25372788
TI  - Haplotype-based analysis of selective sweeps in sheep.
AB  - Domestic animals represent an extremely useful model for linking genotypic and
      phenotypic variation. One approach involves identifying allele frequency
      differences between populations, using F(ST), to detect selective sweeps. While
      simple to calculate, FST may generate false positives due to aspects of
      population history. This prompted the development of hapFLK, a metric that
      measures haplotype differentiation while accounting for the genetic relationship
      between populations. The focus of this paper was to apply hapFLK in sheep with
      available SNP50 genotypes. The hapFLK approach identified a known selective sweep
      on chromosome 10 with high precision. Further, five regions were identified
      centered on genes with strong evidence for positive selection (COL1A2, NCAPG,
      LCORL, and RXFP2). Estimation of global F(ST) revealed many more genomic regions,
      providing empirical data in support of published simulation-based results
      concerning elevated type I error associated with F(ST) when it is being used to
      characterize sweep regions. The findings, while conducted using sheep SNP data,
      are likely to be applicable across those domestic animal species that have
      undergone artificial selection for desirable phenotypic traits.

PMID- 25372789
TI  - Fueling plankton production by a meandering frontal jet: a case study for the
      Alboran Sea (Western Mediterranean).
AB  - A three dimensional biophysical model was employed to illustrate the biological
      impacts of a meandering frontal jet, in terms of efficiency and persistency of
      the autotrophic frontal production, in marginal and semi-enclosed seas. We used
      the Alboran Sea of the Western Mediterranean as a case study. Here, a frontal jet
      with a width of 15-20 km, characterized by the relatively low density Atlantic
      water mass, flows eastward within the upper 100 m as a marked meandering current
      around the western and the eastern anticyclonic gyres prior to its attachment to
      the North African shelf/slope topography of the Algerian basin. Its inherent
      nonlinearity leads to the development of a strong ageostrophic cross-frontal
      circulation that supplies nutrients into the nutrient-starved euphotic layer and
      stimulates phytoplankton growth along the jet. Biological production is larger in
      the western part of the basin and decreases eastwards with the gradual weakening
      of the jet. The higher production at the subsurface levels suggests that the
      Alboran Sea is likely more productive than predicted by the satellite chlorophyll
      data. The Mediterranean water mass away from the jet and the interiors of the
      western and eastern anticyclonic gyres remain unproductive. 

PMID- 25372790
TI  - Clinical and experimental scleroderma 2014.

PMID- 25372791
TI  - Prognostic value of N-terminal natriuretic peptides in systemic sclerosis: a
      single centre study.
AB  - OBJECTIVES: Cardiac involvement is an important determinant of prognosis in
      systemic sclerosis (SSc). The identification of patients with high risk is of
      great importance. Our aim was to investigate the diagnostic and prognostic value
      of circulating concentrations of N-terminal fragments of A- and B-type
      natriuretic peptides (NT-proANP and NT-proBNP) in patients with SSc. METHODS: We
      prospectively studied 144 patients with SSc and followed them up for five years.
      Blood was collected for natriuretic peptide measurement at the time of the yearly
      scheduled cardiological check-up. The occurrence of clinically significant
      cardiac disease was measured as the composite of pulmonary arterial hypertension,
      cardiac revascularisation, development of left ventricular dysfunction or death.
      RESULTS: Patients diagnosed with heart involvement during the study had
      significantly higher levels of NT-proANP and NT-proBNP (791.4 +/- 379.9 pmol/l
      vs. 608.0 +/- 375.8 pmol/l, p<0.05 and 183.1 +/- 162.6 vs. 125.7 +/- 117.5
      pmol/l, p<0.05, respectively). Receiver-operator-characteristic analysis
      identified <822.5 pmol/l as the best NT-proANP and <154.5 pmol/l as the best NT
      proBNP threshold (sensitivity 56.3%, specificity 79.5%, negative predictive
      value: 86.4% and sensitivity 50.0%, specificity 76.8%, negative predictive value:
      83.7%, respectively). During the follow-up, lower NT-proANP levels were
      significantly associated with a longer event-free survival (p<0.05), similar but
      a non-significant trend regarding NT-proBNP levels was also shown (p=0.052).
      CONCLUSIONS: In our cohort, NT-proANP had a supplementary prognostic value for
      cardiac involvement in systemic sclerosis. In addition, the high negative
      predictive value of natriuretic peptides supports the more extensive use in
      identifying SSc patients with high risk of future cardiac involvement.

PMID- 25372792
TI  - Prevalence and predictors of small intestinal bacterial overgrowth in systemic
      sclerosis patients with gastrointestinal symptoms.
AB  - OBJECTIVES: There is a paucity of data available on small intestinal bacterial
      overgrowth (SIBO) in systemic sclerosis (SSc). The objectives of the study were
      to estimate the prevalence of SIBO in SSc patients exhibiting intestinal symptoms
      and identify patients at risk of SIBO regarding clinical and biological
      presentations and gastrointestinal symptoms captured by standardized
      questionnaires. METHODS: Between 2011 and 2012, patients exhibiting intestinal
      complaints underwent glucose H2/CH4 breath tests (BT) and blood assays. They were
      interviewed using the University of California Los Angeles Scleroderma Clinical
      Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GTI) and the
      Short Form-36 (SF-36). For patients diagnosed with SIBO, BT was repeated 1 to 4
      months after the end of antibiotics. RESULTS: Among 120 consecutive patients, 37
      patients (29 women) exhibiting intestinal complaints were included (median age:
      60 years). Fourteen patients (38%) were diagnosed with SIBO; patients from this
      subset had a longer disease duration (p=0.02), a significant weight loss within
      the past 6 months (p=0.03) and a higher total UCLA SCTC GTI score (p=0.03). The
      SF-36 assessment was not discriminant. Among the 14 patients treated for SIBO, 6
      had a negative control BT, 4 remained positive, 2 failed to repeat the test and 2
      patients died due to severe chronic malabsorption. CONCLUSIONS: SIBO is a not
      uncommon, late onset, severe and not easy to treat complication of SSc. Higher
      UCLA SCTC GTI score and weight loss appeared to be strongly associated with SIBO.

PMID- 25372793
TI  - Frequency and impact of disease symptoms experienced by patients with systemic
      sclerosis from five European countries.
AB  - OBJECTIVES: Knowledge about the nature and impact of symptoms faced by patients
      with systemic sclerosis (SSc) is needed to identify targets for research and
      treatment. The aim of this study was to assess and compare the frequency and
      impact on everyday activities of SSc symptoms among patients from five European
      countries. METHODS: European patients with SSc were invited through announcements
      by patient associations to complete an online survey. The survey included items
      assessing the frequency of 40 SSc symptoms and the impact on daily activities, if
      present. Chi-square tests were utilised to assess the differences in frequency
      and impact of symptoms across countries. RESULTS: In total, 537 patients were
      included from France (n=111), the Netherlands (n=229), Spain (n=61), Switzerland
      (n=50), and the United Kingdom (n=86). Symptoms experienced by >= 70% of patients
      in all countries were fatigue, Raynaud's phenomenon, joint pain, and muscle pain.
      Twenty symptoms were experienced by >= 50% of patients in all countries. Thirty
      symptoms had an impact on daily activities in >= 50% of patients who reported
      that the symptom was present in all countries. There were significant differences
      among countries in the prevalence of 17 out of 40 symptoms. Furthermore, in 24
      out of 40 symptoms significant differences in the proportion of patients
      reporting impact of a specific symptom on everyday activities were observed.
      CONCLUSIONS: European patients with SSc experience a broad range of symptoms that
      have an impact on everyday activities. International research initiatives should
      target common SSc symptoms cooperatively. Further research is needed to better
      understand the differences in SSc symptoms among countries.

PMID- 25372794
TI  - GERD questionnaire for diagnosis of gastroesophageal reflux disease in systemic
      sclerosis.
AB  - OBJECTIVES: Gastroesophageal reflux disease (GERD) is clinically-identified in
      patients with systemic sclerosis (SSc). The GERD-questionnaire (GERD-Q) score is
      a sensitive, non-invasive, diagnostic screening tool for diagnosis of GERD in
      general patients, but it has been not investigated for use in SSc. Our aim was to
      evaluate the proper cut-off GERD-Q score, sensitivity and specificity for a
      diagnosis of GERD in SSc patients. METHODS: A cross-sectional study using the
      GERD-Q was performed during May 2012-January 2013 on patients over 18 with the
      diffuse SSc subset. Both esophago-gastro-duodenoscopy (EGD) and 24-hr pH
      monitoring (24hr-pH) were performed as the gold standard tests for both
      symptomatic and asymptomatic GERD. RESULTS: A total of 75 SSc patients completed
      the GERD-Q, EGD and 24hr-pH. We identified 22 males (29.3%), 53 females (70.7%)
      with a mean age of 54.2 years. The respective number of symptomatic and
      asymptomatic GERD was 69 and 6 cases. For a GERD diagnosis, a cut-off GERD-Q
      score of 4 provided the best balance between sensitivity and specificity (96.9%
      and 50%, respectively). Of 48 participants (69.6%) with symptomatic GERD (i.e.
      positive for both EGD and 24hr-pH), 65 (94.2%) were positive for either EGD or
      24hr-pH, and 4 (5.8%) were negative for both EGD and 24hr-pH. A respective
      majority (83%) vs. one-third of the asymptomatic group had reflux as detected by
      24hr-pH vs. EGD CONCLUSIONS: A GERD-Q score of 4 or higher indicates a high
      sensitivity for a diagnosis of GERD in SSc. It can thus be used as a non-invasive
      screening tool for diagnosing GERD in cases where EGD and 24hr-pH are
      unavailable.

PMID- 25372795
TI  - Exercise tolerance in systemic sclerosis patients without pulmonary impairment:
      correlation with clinical variables.
AB  - OBJECTIVES: In systemic sclerosis (SSc) patients pulmonary vasculopathy (PV) is
      present in the early stage of disease and impairs dilation of affected pulmonary
      blood vessels, impeding pulmonary blood flow during exercise. Abnormal gas
      exchange findings were early investigated by cardiopulmonary exercise test
      (CPET). METHODS: A total of 34 female and 6 male [median age 49 (20-63) years]
      SSc patients with normal chest imaging and pulmonary function tests were
      enrolled. Twenty healthy controls age and sex matched [16 female and 4 male;
      median age 51 (35-73) years] were also recruited. All subjects underwent a full
      clinical examination, including a nailfold video capillaros copy (NVC). An
      incremental symptom-limited CPET was performed with estimation of minute
      ventilation (VE), workload (WR), peak oxygen uptake (pVO22), and ventilatory
      efficiency (VE/VCO2 slope). RESULTS: A reduced exercise tolerance (pVO2<80% of
      predicted) was documented in 18 out of 40 subjects (45%). Six out of 18 patients
      with a reduced exercise tolerance showed indirect signs of ventilation perfusion
      mismatch (VE/ VCO2 slope >34). Patients with digital ulcers (DUs) history showed
      VE/VCO2slope values significantly higher [31.4 (18-39.6)] than in patients
      without DUs history [26.9 (22-29.4)] (p<0.0001). VE/VCO2slope values also
      significantly differed between the three capillaroscopic groups: early [26.3 (18
      29.4)], active [28 (26.8-39.6)], and late [32.9 (22.4-39)] (p<0.0001). A positive
      correlation was found between the VE/ VCO2slope and both Disease Activity Index
      (p<0.0001, r=0.59) and Disease Severity Scale (p<0.0001, r=0.73). CONCLUSIONS: In
      SSc patients without evidence of pulmonary and cardiac involvement, CPET might be
      useful in disclosing an early PV.

PMID- 25372796
TI  - Pulmonary hypertension and interstitial lung disease within PHAROS: impact of
      extent of fibrosis and pulmonary physiology on cardiac haemodynamic parameters.
AB  - OBJECTIVES: We sought to examine the relationship between measures of ILD
      severity and PH in patients with SSc. METHODS: We identified 55 subjects from 12
      PHAROS sites with RHC-proven PH and HRCT evidence of ILD. Subjects with PH due to
      left heart disease were excluded. Baseline HRCT scans were scored by a
      standardised system that graded severity of ILD. Summary statistics were
      generated for baseline characteristics. Spearman correlation and linear
      regression were used to examine relationships between ILD and PH severity
      variables. RESULTS: The majority of subjects were white women; nearly half had
      limited cutaneous SSc. Most subjects were New York Heart Association functional
      class II or III. Pulmonary function testing revealed moderate restriction (mean
      FVC 64.3 +/- 17.2% predicted) with severe reduction in diffusing capacity (mean
      DLco 34.2 +/- 13.3% predicted). RHC demonstrated mild to moderate PH (mean PAP 35
      +/- 9 mmHg, mean PVR 5.1 +/- 3.7 WU). There was no correlation between severity
      of ILD (by either HRCT or PFT) and cardiac haemodynamic parameters of PH.
      CONCLUSIONS: No association between severity of ILD and cardiac haemodynamic
      profiles were identified in this cohort. We believe this underscores the complex
      nature of PH and ILD in individuals with SSc. We do suspect that some individuals
      with SSc-ILD will also have concomitant pulmonary vascular disease but simple
      assessments to grade severity of ILD - by PFT or HRCT estimates of ILD extent -
      are likely not enough to reliably distinguish between PAH versus PH-ILD. Further
      research into how to distinguish and manage these subsets is warranted.

PMID- 25372797
TI  - Clinical and laboratory characteristics of systemic sclerosis patients with
      pulmonary arterial hypertension in China.
AB  - OBJECTIVES: Pulmonary arterial hypertension (PAH) is associated with significant
      morbidity and mortality, especially in systemic sclerosis (SSc). Since there was
      no published study regarding PAH in the Chinese SSc population, we aimed to
      describe a cohort to provide some data for early diagnosis. METHODS: We evaluated
      236 systemic sclerosis patients prospectively registered in the EUSTAR (European
      League Against Rheumatism Scleroderma Trial and Research Group) database from the
      Peking Union Medical College Hospital from 2009 to 2012. Among them, 33
      individuals received right heart catheterisations (RHC) while the remaining
      patients were grouped by echocardiographic data. These patients were classified
      into two groups, PAH and non-PAH group. Their clinical and laboratory features
      were statistically analysed to identify possible risk factors for PAH in Chinese
      SSc population. RESULTS: The possible prevalence of PAH in SSc patients was
      approximately 11% in our study. Digital ulcers (52.0% vs. 31.2%), telangiectasias
      (64.0% vs. 37.6%) and gastroesophageal reflux disease (GERD) (60.0% vs. 36.2%)
      were more common in SSc patients with PAH. Some laboratory results were also
      proved to be significantly correlated with it. Logistic regression analysis
      showed that telangiectasias (OR=2.888, 95% CI=1.176-7.093), presence of GERD
      (OR=2.592, 95% CI=1.067-6.296), anti-RNP positivity (OR=24.384, 95% CI=1.978
      36.651), IgA level elevation (OR=8.745, 95% CI 4.838-122.896) and FVC/TLCO ratio
      (OR=97.067, 95% CI 12.475-755.271) were associated with an increased odds for PAH
      in SSc patients. CONCLUSIONS: This study described possible predictors of PAH in
      Chinese SSc population, which have been supported by similar studies in other
      ethnic groups.

PMID- 25372798
TI  - A cautionary tale: dealing with missing data in clinical trials for rheumatic
      diseases.
AB  - OBJECTIVES: Missing data are found in nearly all clinical trials and it is
      important to use appropriate statistical techniques to analyse clinical trials
      with missing data. We discuss common statistical methods for tackling missing
      data and how to handle results when the analyses give different results. METHODS:
      Using data from a placebo-controlled, randomised bovine Type I collagen (CI)
      study in diffuse cutaneous systemic sclerosis (dcSSc), we apply different
      statistical approaches to handling missing data. We also describe simple ways to
      ascertain the type of missing data in the data set, to the extent possible.
      RESULTS: We examine eleven different methods to impute missing data. An analysis
      based on completers alone (complete case analysis and available case analysis)
      and the last observation carried forward (LOCF) methods require underlying
      assumptions which are rarely met in practice. Multiple imputation, mixed effects,
      and repeated measures try to account for the differences among patients and
      account for patient's specific response patterns, although the assumption that
      the missing data is directly related to the observed characteristics may well not
      be true. The joint likelihood based model combines the mixed effect model and
      logistic regression model to explicitly handle data not missing at random and so
      it is more realistic and potentially takes an additional step toward decreasing
      bias. CONCLUSIONS: We discussed various ways of handling missing data and provide
      recommendations on how to arrive at a conclusion when different statistical
      approaches to analyse missing data analysis in clinical trials give conflicting
      answers.

PMID- 25372799
TI  - Endothelial dysfunction is present only in the microvasculature and
      microcirculation of early diffuse systemic sclerosis patients.
AB  - OBJECTIVES: To evaluate endothelial function and vascular stiffness in large,
      medium, small and microcirculatory blood vessels in very early diffuse systemic
      sclerosis (SSc). METHODS: We studied consecutive early diffuse SSc patients,
      defined as <2 years from first SSc symptom who did not have a prior
      cardiovascular event. Age, gender and race-matched controls were recruited. All
      underwent assessment of aortic pulse wave velocity (PWV), carotid intima-media
      thickness (IMT) brachial flow-mediated dilation (FMD), digital peripheral artery
      tonometer (EndoPAT) assessment and laser speckle contrast imaging (LSCI).
      RESULTS: Fifteen early diffuse SSc and controls were evaluated. The average age
      was 49 years, 63% were female and 93% were Caucasian. There were no differences
      in body mass index, hypertension, diabetes or hyperlipidaemia between controls
      and SSc patients. Mean SSc disease duration was 1.3 years. In the large central
      vessels, there was no difference in aortic PWV (p=0.71) or carotid IMT (p=0.92)
      between SSc patients and controls. Similarly, there was no difference in
      endothelial dysfunction with brachial artery FMD after ischaemia (p=0.55) and
      nitroglycerin administration (p=0.74). There were significantly lower values for
      digital EndoPAT measures (p=0.0001) in SSc patients. LSCI revealed a distinct
      pattern of microcirculatory abnormalities in response to ischaemia in SSc
      patients compared to controls. Imaging demonstrated a blunted microcirculatory
      hyperaemia of the hand with greater subsequent response to nitroglycerin.
      CONCLUSIONS: These findings suggest that the earliest endothelial changes occur
      in smaller arterioles and microvascular beds, but not in medium or macrovascular
      beds, in early diffuse SSc.

PMID- 25372800
TI  - Measurement of interatrial dyssynchrony using tissue Doppler imaging predicts
      functional capacity and cardiac involvement in systemic sclerosis.
AB  - OBJECTIVES: We aimed to assess the prevalence of interatrial electromechanical
      dyssynchrony in systemic sclerosis (SSc) patients, and to study the correlation
      between interatrial delay and standard follow-up parameters. METHODS: Forty
      consecutive patients with SSc were studied. Classical echocardiographic
      measurements were obtained, including indices of left ventricular (LV) systolic
      and diastolic function, right ventricular function, and pulmonary artery pressure
      (PAP). Left atrial (LA) function was studied using volume measurements. The
      interatrial mechanical (IAMD) delay was obtained by measuring the time delay
      between the peak atrial velocities at the lateral tricuspid and mitral annuli
      using tissue Doppler imaging. A cut-off value of 35 ms was chosen to define the
      presence of a significant interatrial delay. The IAMD was compared to NYHA class,
      six-minute walking test (6MWT), NT proBNP levels, and the carbon monoxide
      diffusion capacity over alveolar volume ratio (DLCO/VA), as well as to classical
      echocardiographic parameters. RESULTS: Forty percent of patients were found to
      have significant interatrial dyssynchrony with an IAMD of 35 ms or more. Patients
      with interatrial dyssynchrony were more symptomatic, had a shorter 6MWT, higher
      NT proBNP levels, and a lower DLCO/VA compared with those without dyssynchrony.
      Regarding conventional echocardiographic parameters, increased IAMD was
      associated with more pronounced LV diastolic dysfunction, LA enlargement and
      dysfunction, altered RV function, and higher PAP. CONCLUSIONS: IAMD correlated
      with all of the standard follow-up parameters in SSc, and is probably a sensitive
      marker of LA involvement. This easy to measure parameter should be added to the
      routine echocardiographic assessment of these patients.

PMID- 25372802
TI  - Systemic sclerosis: a critical digest of the recent literature.
AB  - Systemic sclerosis is a complex disease characterised by chronic multisystem
      involvement of internal organs; every year many studies are published on the
      diagnosis, pathogenesis and treatment of the disease. In this article, we provide
      a critical analysis of the recent literature on systemic sclerosis, with
      particular focus on the most relevant studies published over the last two years. 

PMID- 25372801
TI  - Anti-SSA/Ro52 autoantibodies in scleroderma: results of an observational, cross
      sectional study.
AB  - OBJECTIVES: To date, the diagnostic utility of anti-SSA/Ro52 autoantibodies in
      scleroderma and the association of them with certain clinical manifestations,
      particularly inflammatory myositis, are still controversial. This paper aims to
      assess the correlation between the presence of anti-SSA/Ro52 antibodies and the
      demographic, clinical and prognosis characteristics of patients with systemic
      sclerosis (SSc). METHODS: This is a retrospective, cross-sectional and
      observational study in patients with SSc. Baseline demographic and clinical
      characteristics were recorded. Presence of anti-SSA/Ro52, anti-SSA/Ro, anti
      SSB/La, snRNP/Sm, anti-centromere, anti-Scl-70 and anti-PM-Scl were analysed by
      immunoblot, and antinuclear antibodies (ANA) by indirect immunofluorescence.
      Statistical analysis was performed with PASW Statics 18 software. RESULTS: A
      total of 132 consecutive patients with analysis of anti-SSA/Ro52 antibodies were
      selected from a Spanish cohort of 408 patients with SSc, 87.1% of them being
      women. About half of patients had the limited form (51.5%), followed by diffused
      form (18.9%), sclerosis sine scleroderma (22.7%), and pre-scleroderma (6.8%).
      Prevalence of anti-SSA/Ro52 was 35.6%. No association between anti-SSA/Ro52 and
      clinical manifestations was found, while detection of anti-SSA/Ro52 was
      significantly associated with the presence of anti-Ro. CONCLUSIONS: The results
      of our study show that anti-SSA/Ro52 antibodies are often found in SSc patients.
      No clinical manifestations, including inflammatory myopathy, were related with
      anti-SSA/Ro antibodies.

PMID- 25372803
TI  - Work participation in patients with systemic sclerosis: a systematic review.
AB  - OBJECTIVES: With this systematic review an overview is given of what is known
      about work participation in patients with systemic sclerosis (SSc). METHODS: The
      databases Pubmed, Cinahl, Nursing and Allied Health and PsychARTICLES have been
      checked from 1980 onwards. The search string consisted of all combinations of key
      words for work participation and SSc. Two investigators evaluated the eligibility
      for the articles. Reference lists were searched for other studies. RESULTS: Eight
      quantitative and one qualitative study were scrutinised in depth. The percentage
      of patients not working ranges from 18% to 61%. A meta-analysis of the percentage
      patients not working was performed and a weight mean of 37% was found. The
      following parameters are associated with the work variable in multivariate
      analysis (number of studies in which the variable was independently associated
      with the work variable/number of studies in which the variable was multivariately
      assessed): global disability (4/5), health (3/5), educational level (2/4),
      disease duration (3/3), skin/lung involvement (1/3), age/fatigue/muscle
      involvement/hand function (1/2) and having a decreased income/race/social
      support/physically demanding job (1/1). In the qualitative study, management of
      the work situation, disclosure of limitations at the work force and adaptation of
      resources in daily life are discussed. CONCLUSIONS: Most studies concerning work
      participation are at this very moment quantitative and cross-sectionally
      designed. Longitudinal studies are needed to assess causality and qualitative
      research may be opportune to have a more comprehensive view on the topic of work
      participation in patients with SSc.

PMID- 25372804
TI  - Consensus best practice pathway of the UK scleroderma study group:
      gastrointestinal manifestations of systemic sclerosis.
AB  - Systemic sclerosis is an autoimmune connective tissue disorder, which can be
      progressive with multisystem involvement. Guidance on the management of
      complications is based on a limited data set and practice amongst clinicians can
      vary. The UK Scleroderma study group set up several working groups to agree some
      consensus pathways for the management of specific complications. Approximately
      nine out of ten patients with systemic sclerosis will have involvement of the
      gastrointestinal system and in this review article we explore the management of
      these complications in a symptom-based approach. The algorithms are a useful tool
      for clinicians, which we hope, will be a point of reference and highlight the
      need for further research in these areas. 

PMID- 25372805
TI  - The impact of magnetic resonance imaging in early diagnosis of hand osteomyelitis
      in patients with systemic sclerosis.

PMID- 25372806
TI  - Kidney biopsy is mandatory in cases of 'silent' arterial hypertension in
      scleroderma renal crisis: a case report.

PMID- 25372807
TI  - Scleromyxedema complicated by dermato-neuro syndrome during pregnancy.

PMID- 25372808
TI  - Social hierarchies and emotions: cortical prefrontal activity, facial feedback
      (EMG), and cognitive performance in a dynamic interaction.
AB  - In the present research, we manipulated the perceived superior/inferior status
      during a competitive cognitive task. In two experiments, we created an explicit
      and strongly reinforced social hierarchy based on incidental rating on an
      attentional task. Based on our hypotheses, social rank may influence nonverbal
      cues (such as facial mimic related to emotional response), cortical lateralized
      activity in frontal areas (brain oscillations), and cognitive outcomes in
      response to rank modulation. Thus, the facial mimic (corrugators vs. zygomatic
      muscle activity), frequency bands (delta, theta, alpha, beta), and real cognitive
      performance [(error rate (ER); response times (RTs)] were considered.
      Specifically, a peer-group comparison was enrolled and an improved (experiment 1,
      N = 29) or decreased (experiment 2, N = 31) performance was artificially
      manipulated by the experimenter. Results showed a significant improved cognitive
      performance (decreased ER and RTs), an increased zygomatic activity (positive
      emotions), and a more prefrontal left-lateralized cortical response in the case
      of a perceived increased social ranking. On the contrary, a significant decreased
      cognitive performance (increased ER and RTs), an increased corrugators activity
      (negative emotions), and a less left-lateralized cortical response were observed
      as a consequence of a perceived decreased social ranking. Moreover, the
      correlational values revealed a consistent trend between behavioral (RTs) and EMG
      and EEG measures for both experiments. The present results suggest that social
      status not only guides social behavior, but it also influences cognitive
      processes and subjects' performance. 

PMID- 25372809
TI  - The relationship between event-based prospective memory and ongoing task
      performance in chimpanzees (Pan troglodytes).
AB  - Prospective memory is remembering to do something at a future time. A growing
      body of research supports that prospective memory may exist in nonhuman animals,
      but the methods used to test nonhuman prospective memory differ from those used
      with humans. The current work tests prospective memory in chimpanzees using a
      method that closely approximates a typical human paradigm. In these experiments,
      the prospective memory cue was embedded within an ongoing task. Tokens
      representing food items could be used in one of two ways: in a matching task with
      pictures of items (the ongoing task) or to request a food item hidden in a
      different location at the beginning of the trial. Chimpanzees had to disengage
      from the ongoing task in order to use the appropriate token to obtain a higher
      preference food item. In Experiment 1, chimpanzees effectively matched tokens to
      pictures, when appropriate, and disengaged from the ongoing task when the token
      matched the hidden item. In Experiment 2, performance did not differ when the
      target item was either hidden or visible. This suggested no effect of cognitive
      load on either the prospective memory task or the ongoing task, but performance
      was near ceiling, which may have contributed to this outcome. In Experiment 3, we
      created a more challenging version of the task. More errors on the matching task
      occurred before the prospective memory had been carried out, and this difference
      seemed to be limited to the hidden condition. This finding parallels results from
      human studies and suggests that working memory load and prospective memory may
      have a similar relationship in nonhuman primates. 

PMID- 25372811
TI  - New crystal structures of adenylate kinase from Streptococcus pneumoniae D39 in
      two conformations.
AB  - Adenylate kinases (AdKs; EC 2.7.3.4) play a critical role in intercellular
      homeostasis by the interconversion of ATP and AMP to two ADP molecules. Crystal
      structures of adenylate kinase from Streptococcus pneumoniae D39 (SpAdK) have
      recently been determined using ligand-free and inhibitor-bound crystals belonging
      to space groups P21 and P1, respectively. Here, new crystal structures of SpAdK
      in ligand-free and inhibitor-bound states determined at 1.96 and 1.65 A
      resolution, respectively, are reported. The new ligand-free crystal belonged to
      space group C2, with unit-cell parameters a=73.5, b=54.3, c=62.7 A, beta=118.8
      degrees . The new ligand-free structure revealed an open conformation that
      differed from the previously determined conformation, with an r.m.s.d on Calpha
      atoms of 1.4 A. The new crystal of the complex with the two-substrate-mimicking
      inhibitor P1,P5-bis(adenosine-5'-)pentaphosphate (Ap5A) belonged to space group
      P1, with unit-cell parameters a=53.9, b=62.3, c=63.0 A, alpha=101.9, beta=112.6,
      gamma=89.9 degrees . Despite belonging to the same space group as the previously
      reported crystal, the new Ap5A-bound crystal contains four molecules in the
      asymmetric unit, compared with two in the previous crystal, and shows slightly
      different lattice contacts. These results demonstrate that SpAdK can crystallize
      promiscuously in different forms and that the open structure is flexible in
      conformation.

PMID- 25372810
TI  - Optimization of crystallization conditions for biological macromolecules.
AB  - For the successful X-ray structure determination of macromolecules, it is first
      necessary to identify, usually by matrix screening, conditions that yield some
      sort of crystals. Initial crystals are frequently microcrystals or clusters, and
      often have unfavorable morphologies or yield poor diffraction intensities. It is
      therefore generally necessary to improve upon these initial conditions in order
      to obtain better crystals of sufficient quality for X-ray data collection. Even
      when the initial samples are suitable, often marginally, refinement of conditions
      is recommended in order to obtain the highest quality crystals that can be grown.
      The quality of an X-ray structure determination is directly correlated with the
      size and the perfection of the crystalline samples; thus, refinement of
      conditions should always be a primary component of crystal growth. The
      improvement process is referred to as optimization, and it entails sequential,
      incremental changes in the chemical parameters that influence crystallization,
      such as pH, ionic strength and precipitant concentration, as well as physical
      parameters such as temperature, sample volume and overall methodology. It also
      includes the application of some unique procedures and approaches, and the
      addition of novel components such as detergents, ligands or other small molecules
      that may enhance nucleation or crystal development. Here, an attempt is made to
      provide guidance on how optimization might best be applied to crystal-growth
      problems, and what parameters and factors might most profitably be explored to
      accelerate and achieve success. 

PMID- 25372812
TI  - Structure of the methanofuran/methanopterin-biosynthetic enzyme MJ1099 from
      Methanocaldococcus jannaschii.
AB  - Prior studies have indicated that MJ1099 from Methanocaldococcus jannaschii has
      roles in the biosynthesis of tetrahydromethanopterin and methanofuran, two key
      cofactors of one-carbon (C1) metabolism in diverse organisms including the
      methanogenic archaea. Here, the structure of MJ1099 has been solved to 1.7 A
      resolution using anomalous scattering methods. The results indicate that MJ1099
      is a member of the TIM-barrel superfamily and that it is a homohexamer.
      Bioinformatic analyses identified a potential active site that is highly
      conserved among MJ1099 homologs and the key amino acids involved were identified.
      The results presented here should guide further studies of MJ1099 including
      mechanistic studies and possibly the development of inhibitors that target the
      methanogenic archaea in the digestive tracts of humans and that are a source of
      the greenhouse gas methane. 

PMID- 25372813
TI  - The structure of rice weevil pectin methylesterase.
AB  - Rice weevils (Sitophilus oryzae) use a pectin methylesterase (EC 3.1.1.11), along
      with other enzymes, to digest cell walls in cereal grains. The enzyme is a right
      handed beta-helix protein, but is circularly permuted relative to plant and
      bacterial pectin methylesterases, as shown by the crystal structure determination
      reported here. This is the first structure of an animal pectin methylesterase.
      Diffraction data were collected to 1.8 A resolution some time ago for this
      crystal form, but structure solution required the use of molecular-replacement
      techniques that have been developed and similar structures that have been
      deposited in the last 15 years. Comparison of the structure of the rice weevil
      pectin methylesterase with that from Dickeya dandantii (formerly Erwinia
      chrysanthemi) indicates that the reaction mechanisms are the same for the insect,
      plant and bacterial pectin methylesterases. The similarity of the structure of
      the rice weevil enzyme to the Escherichia coli lipoprotein YbhC suggests that the
      evolutionary origin of the rice weevil enzyme was a bacterial lipoprotein, the
      gene for which was transferred to a primitive ancestor of modern weevils and
      other Curculionidae. Structural comparison of the rice weevil pectin
      methylesterase with plant and bacterial enzymes demonstrates that the rice weevil
      protein is circularly permuted relative to the plant and bacterial molecules. 

PMID- 25372814
TI  - Structure of type II dehydroquinase from Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa causes opportunistic infections and is resistant to most
      antibiotics. Ongoing efforts to generate much-needed new antibiotics include
      targeting enzymes that are vital for P. aeruginosa but are absent in mammals. One
      such enzyme, type II dehydroquinase (DHQase), catalyzes the interconversion of 3
      dehydroquinate and 3-dehydroshikimate, a necessary step in the shikimate pathway.
      This step is vital for the proper synthesis of phenylalanine, tryptophan,
      tyrosine and other aromatic metabolites. The recombinant expression, purification
      and crystal structure of catalytically active DHQase from P. aeruginosa
      (PaDHQase) are presented. Cubic crystals belonging to space group F23, with unit
      cell parameters a=b=c=125.39 A, were obtained by vapor diffusion in sitting drops
      and the structure was refined to an R factor of 16% at 1.74 A resolution.
      PaDHQase is a prototypical type II DHQase with the classical flavodoxin-like
      alpha/beta topology.

PMID- 25372815
TI  - Structure of an Escherichia coli Hfq:RNA complex at 0.97 A resolution.
AB  - In bacteria, small RNAs (sRNAs) silence or activate target genes through base
      pairing with the mRNA, thereby modulating its translation. A central player in
      this process is the RNA chaperone Hfq, which facilitates the annealing of sRNAs
      with their target mRNAs. Hfq has two RNA-binding surfaces that recognize A-rich
      and U-rich sequences, and is believed to bind an sRNA-mRNA pair simultaneously.
      However, how Hfq promotes annealing remains unclear. Here, the crystal structure
      of Escherichia coli Hfq is presented in complex with U6-RNA bound to its proximal
      binding site at 0.97 A resolution, revealing the Hfq-RNA interaction in
      exceptional detail. 

PMID- 25372816
TI  - Ovine beta-lactoglobulin at atomic resolution.
AB  - The crystal structure of the triclinic form of the milk protein beta
      lactoglobulin from sheep (Ovis aries) at 1.1 A resolution is described together
      with a comparison of the triclinic structures of the low-pH bovine and high-pH
      ovine proteins. All three structures are remarkably similar, despite the well
      known pH-dependent conformational transition described for the bovine and porcine
      proteins that occurs in solution. The high resolution of the present structure
      determination has allowed a more accurate description of the protein than has
      hitherto been possible, but it is still not clear whether flexibility changes in
      the external loops can compensate for the presence of a significant void in the
      unliganded interior of the structure. 

PMID- 25372817
TI  - Production, crystallization and preliminary X-ray diffraction of the Galphas
      alpha-helical domain in complex with a nanobody.
AB  - GPCR-G-protein complexes are one of the most important components of cell
      signalling cascades. Extracellular signals are sensed by membrane-associated G
      protein-coupled receptors (GPCRs) and transduced via G proteins towards
      intracellular effector molecules. Structural studies of these transient complexes
      are crucial to understand the molecular details of these interactions. Although a
      nucleotide-free GPCR-G-protein complex is stable, it is not an ideal sample for
      crystallization owing to the intrinsic mobility of the Galphas alpha-helical
      domain (AHD). To stabilize GPCR-G-protein complexes in a nucleotide-free form,
      nanobodies were selected that target the flexible GalphasAHD. One of these
      nanobodies, CA9177, was co-crystallized with the GalphasAHD. Initial crystals
      were obtained using the sitting-drop method in a sparse-matrix screen and further
      optimized. The crystals diffracted to 1.59 A resolution and belonged to the
      monoclinic space group P21, with unit-cell parameters a=44.07, b=52.55, c=52.66
      A, alpha=90.00, beta=107.89, gamma=90.00 degrees . The structure of this specific
      nanobody reveals its binding epitope on GalphasAHD and will help to determine
      whether this nanobody could be used as crystallization chaperone for GPCR-G
      protein complexes.

PMID- 25372818
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of NADP
      dependent glutamate dehydrogenase from Aspergillus niger.
AB  - Glutamate dehydrogenase (GDH) catalyzes the NAD-dependent or NADP-dependent
      oxidative deamination of L-glutamate to 2-oxoglutarate and ammonia. This
      important reversible reaction establishes the link between carbon and nitrogen
      metabolism. In this study, Aspergillus niger NADP-GDH (AnGDH) has been
      overexpressed and purified. Purified AnGDH, with a high specific activity of
      631.1 units per milligram of protein, was crystallized and the crystal diffracted
      to 2.9 A resolution using a home X-ray source. Preliminary analysis of the X-ray
      diffraction data showed that the crystal belonged to space group R32, with unit
      cell parameters a=b=173.8, c=241.5 A, alpha=beta=90, gamma=120 degrees . The
      crystals exhibited an unusually high solvent content (83.0%) and had only one
      molecule in the asymmetric unit. Initial phases were obtained by molecular
      replacement, and model building and structure refinement of AnGDH are in
      progress.

PMID- 25372819
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      characterization of allantoinase from Bacillus licheniformis ATCC 14580.
AB  - Allantoinase, a member of the amidohydrolase superfamily, exists in a wide
      variety of organisms, including bacteria, fungi, plants and a few animals, such
      as fishes and amphibians. Allantoinase catalyzes the reversible hydrolysis of
      allantoin into allantoate by hydrolytic cleavage of the N1-C2 amide bond of the
      five-membered hydantoin ring. Allantoinase from Bacillus licheniformis (AllBali)
      presents an inverted enantioselectivity towards allantoin (R-enantioselective),
      which is a distinguishable feature that is not observed for other allantoinases.
      In this work, B. licheniformis ATCC 14580 allantoinase (AllBali) containing a C
      terminal His6 tag was overproduced in Escherichia coli and purified to
      homogeneity. Crystals of AllBali were obtained by the vapour-diffusion method
      using 0.1 M potassium thiocyanate, 20%(w/v) polyethylene glycol 3350 as a
      crystallization solution. X-ray diffraction data were collected to a resolution
      of 3.5 A with an Rmerge of 29.2% from a crystal belonging to space group P1211,
      with unit-cell parameters a=54.93, b=164.74, c=106.89 A, beta=98.49 degrees .
      There are four molecules in the asymmetric unit with a solvent content of 47% as
      estimated from the Matthews coefficient (VM=2.34 A3 Da(-1)).

PMID- 25372820
TI  - Overproduction, crystallization and preliminary X-ray crystallographic analysis
      of Escherichia coli tRNA N6-threonylcarbamoyladenosine dehydratase.
AB  - Escherichia coli tRNA N6-threonylcarbamoyladenosine dehydratase (TcdA),
      previously called CsdL or YgdL, was overproduced and purified from E. coli and
      crystallized using polyethylene glycol 3350 as a crystallizing agent. X-ray
      diffraction data were collected to 2.70 A resolution under cryoconditions using
      synchrotron X-rays. The crystals belonged to space group P21, with unit-cell
      parameters a=65.4, b=96.8, c=83.3 A, beta=111.7 degrees . According to the
      Matthews coefficient, the asymmetric unit may contain up to four subunits of the
      monomeric protein, with a crystal volume per protein mass (VM) of 2.12 A3 Da(-1)
      and 42.1% solvent content.

PMID- 25372821
TI  - Crystallization and preliminary X-ray crystallographic analysis of an artificial
      molten-globular-like triosephosphate isomerase protein of mixed phylogenetic
      origin.
AB  - A bioinformatics-based protein-engineering approach called consensus design led
      to the construction of a chimeric triosephosphate isomerase (TIM) protein called
      ccTIM (curated consensus TIM) which is as active as Saccharomyces cerevisiae TIM
      despite sharing only 58% sequence identity with it. The amino-acid sequence of
      this novel protein is as identical to native sequences from eukaryotes as to
      those from prokaryotes and shares some biophysical traits with a molten globular
      protein. Solving its crystal structure would help in understanding the physical
      implications of its bioinformatics-based sequence. In this report, the ccTIM
      protein was successfully crystallized using the microbatch-under-oil method and a
      full X-ray diffraction data set was collected to 2.2 A resolution using a
      synchrotron-radiation source. The crystals belonged to space group C2221, with
      unit-cell parameters a=107.97, b=187.21, c=288.22 A. Matthews coefficient
      calculations indicated the presence of six dimers in the asymmetric unit, with an
      approximate solvent content of 46.2%.

PMID- 25372822
TI  - Purification, crystallization, preliminary X-ray diffraction and molecular
      replacement studies of great cormorant (Phalacrocorax carbo) haemoglobin.
AB  - Haemoglobin is the iron-containing oxygen-transport metalloprotein that is
      present in the red blood cells of all vertebrates. In recent decades, there has
      been substantial interest in attempting to understand the structural basis and
      functional diversity of avian haemoglobins. Towards this end, purification,
      crystallization, preliminary X-ray diffraction and molecular-replacement studies
      have been carried out on cormorant (Phalacrocorax carbo) haemoglobin. Crystals
      were grown by the hanging-drop vapour-diffusion method using PEG 3350, NaCl and
      glycerol as precipitants. The crystals belonged to the trigonal system P3121,
      with unit-cell parameters a=b=55.64, c=153.38 A, beta=120.00 degrees ; a complete
      data set was collected to a resolution of 3.5 A. Matthews coefficient analysis
      indicated that the crystals contained a half-tetramer in the asymmetric unit.

PMID- 25372823
TI  - Crystallization and preliminary X-ray diffraction data of beta-galactosidase from
      Aspergillus niger.
AB  - beta-Galactosidase from Aspergillus niger (An-beta-Gal), belonging to the family
      35 glycoside hydrolases, hydrolyzes the beta-galactosidase linkages in lactose
      and other galactosides. It is extensively used in industry owing to its high
      hydrolytic activity and safety. The enzyme has been expressed in yeasts and
      purified by immobilized metal-ion affinity chromatography for crystallization
      experiments. The recombinant An-beta-Gal, deglycosylated to avoid heterogeneity
      of the sample, has a molecular mass of 109 kDa. Rod-shaped crystals grew using
      PEG 3350 as the main precipitant agent. A diffraction data set was collected to
      1.8 A resolution. 

PMID- 25372824
TI  - In situ proteolysis, crystallization and preliminary X-ray diffraction analysis
      of a VHH that binds listeria internalin B.
AB  - The variable region of camelid heavy-chain antibodies produces the smallest known
      antibody fragment with antigen-binding capability (a VHH). The VHH R303 binds
      internalin B (InlB), a virulence factor expressed by the pathogen Listeria
      monocytogenes. InlB is critical for initiation of Listeria infection, as it binds
      a receptor (c-Met) on epithelial cells, triggering the entry of bacteria into
      host cells. InlB is surface-exposed and is required for virulence, hence a VHH
      targeting InlB has potential applications for pathogen detection or therapeutic
      intervention. Here, the expression, purification, crystallization and X-ray
      diffraction of R303 are reported. Crystals of R303 were obtained following in
      situ proteolysis with trypsin. Gel filtration and SDS-PAGE revealed that trypsin
      removed the C-terminal tag region of R303, facilitating crystal formation.
      Crystals of R303 diffracted to 1.3 A resolution and belonged to the monoclinic
      space group P21, with unit-cell parameters a=46.4, b=31.2, c=74.8 A, beta=93.8
      degrees . The crystals exhibited a Matthews coefficient of 1.95 A3 Da(-1) with
      two molecules in the asymmetric unit.

PMID- 25372825
TI  - Expression, purification, crystallization and preliminary X-ray crystallographic
      analysis of the extracellular olfactomedin domain of gliomedin.
AB  - Gliomedin (GLDN) is one of the essential proteins in the development of the nodes
      of Ranvier in the vertebrate peripheral nervous system. An olfactomedin (OLF)
      domain is located at the GLDN extracellular C-terminus and is involved in the
      accumulation of neuronal plasma membrane voltage-gated sodium channels in the
      nodes by interacting with neurofascin and NrCAM. No structures of OLF domains
      have previously been reported. Here, the crystallization of the rat GLDN OLF
      domain, which was expressed in an insect-cell system, is reported. The crystal
      diffracted to 1.55 A resolution and belonged to space group P21, with unit-cell
      parameters a=37.5, b=141.7, c=46.0 A, beta=110.6 degrees , and had two molecules
      in the asymmetric unit.

PMID- 25372826
TI  - Purification, crystallization and preliminary crystallographic investigation of
      FrnE, a disulfide oxidoreductase from Deinococcus radiodurans.
AB  - In prokaryotes, Dsb proteins catalyze the formation of native disulfide bonds
      through an oxidative folding pathway and are part of the cell machinery that
      protects proteins from oxidative stress. Deinococcus radiodurans is an
      extremophile which shows unparalleled resistance to ionizing radiation and
      oxidative stress. It has a strong mechanism to protect its proteome from
      oxidative damage. The genome of Deinococcus shows the presence of FrnE, a Dsb
      protein homologue that potentially provides the bacterium with oxidative stress
      tolerance. Here, crystallization and preliminary X-ray crystallographic analysis
      of FrnE from D. radiodurans are reported. Diffraction-quality single crystals
      were obtained using the hanging-drop vapour-diffusion method with reservoir
      solution consisting of 100 mM sodium acetate pH 5.0, 10% PEG 8000, 15-20%
      glycerol. Diffraction data were collected on an Agilent SuperNova system using a
      microfocus sealed-tube X-ray source. The crystal diffracted to 1.8 A resolution
      at 100 K. The space group of the crystal was found to be P21221, with unit-cell
      parameters a=47.91, b=62.94, c=86.75 A, alpha=beta=gamma=90 degrees . Based on
      Matthews coefficient analysis, one monomer per asymmetric unit is present in the
      crystal, with a solvent content of approximately 45%.

PMID- 25372827
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      the flagellar accessory protein FlaH from the methanogenic archaeon
      Methanocaldococcus jannaschii.
AB  - The flagellar accessory protein FlaH is thought to be one of the essential
      components of an archaeal motility system. However, to date biochemical and
      structural information about this protein has been limited. Here, the
      crystallization of FlaH from the hyperthermophilic archaeon Methanocaldococcus
      jannaschii is reported. Protein crystals were obtained by the vapour-diffusion
      method. These crystals belonged to space group P3121, with unit-cell parameters
      a=b=131.42, c=89.35 A. The initial solution of the FlaH structure has been
      determined by multiple-wavelength anomalous dispersion phasing using a
      selenomethionine-derivatized crystal.

PMID- 25372828
TI  - Use of a novel microtitration protocol to obtain diffraction-quality crystals of
      4-hydroxy-2-oxoglutarate aldolase from Bos taurus.
AB  - The enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA) catalyses the retro-aldol
      degradation of 4-hydroxy-2-oxoglutarate to pyruvate and glyoxylate as part of the
      hydroxyproline catabolic pathway in mammals. Mutations in the coding region of
      the human HOGA gene are associated with primary hyperoxaluria type 3, a disease
      characterized by excessive oxalate production and ultimately stone deposition.
      Native HOGA was purified from bovine kidney using an improved and streamlined
      purification protocol from which two crystal forms were obtained using two
      different approaches. Vapour diffusion using PEG 3350 as a precipitant produced
      monoclinic crystals that belonged to space group C2 and diffracted to 3.5 A
      resolution. By comparison, orthorhombic crystals belonging to space group I222 or
      I212121 and diffracting to beyond 2.25 A resolution were obtained using a novel
      microtitration protocol with ammonium sulfate. The latter crystal form displayed
      superior diffraction quality and was suitable for structural determination by X
      ray crystallography.

PMID- 25372829
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of
      pyridoxal kinase from Plasmodium falciparum (PfPdxK).
AB  - Pyridoxal kinases (PdxK) catalyze the phosphorylation of vitamin B6 precursors.
      Thus, these enzymes are an essential part of many metabolic processes in all
      organisms. The protozoan parasite Plasmodium falciparum (the main causative agent
      of Malaria tropica) possesses a unique de novo B6-biosynthesis pathway in
      addition to a interconversion pathway based on the activity of plasmodial PdxK
      (PfPdxK). The role of PdxK in B6 salvage has prompted previous authors to suggest
      PdxK as a promising target for structure-based antimalarial drug design. Here,
      the expression, purification, crystallization and preliminary X-ray diffraction
      analysis of PfPdxK are reported. PfPdxK crystals have been grown in space group
      P21, with unit-cell parameters a=52.7, b=62.0, c=93.7 A, beta=95 degrees . A data
      set has been collected to 2 A resolution and an initial molecular-replacement
      solution is described.

PMID- 25372831
TI  - Crystallization and preliminary X-ray analysis of the hypothetical deaminase
      RPB_0146 from Rhodopseudomonas palustris HaA2.
AB  - RPB_0146, a putative deaminase from Rhodopseudomonas palustris HaA2, was
      expressed in Escherichia coli BL21 (DE3) cells and purified using a His6 tag by
      Ni2+-chelating affinity chromatography for X-ray crystallographic analysis.
      Diffraction-quality crystals were grown by the hanging-drop vapour-diffusion
      method at 289 K and diffracted to a resolution of 2.44 A using a wavelength of
      1.000 A at the Photon Factory (KEK), Japan. The crystals belonged to the
      orthorhombic space group P212121, with unit-cell parameters a=66.26, b=123.94,
      c=155.95 A.

PMID- 25372830
TI  - Crystallization and preliminary X-ray diffraction studies of an L-amino-acid
      oxidase from Lachesis muta venom.
AB  - Snake-venom proteins form multi-component defence systems by the recruitment and
      rapid evolution of nonvenomous proteins and hence serve as model systems to
      understand the structural modifications that result in toxicity. L-Amino-acid
      oxidases (LAAOs) are encountered in a number of snake venoms and have been
      implicated in the inhibition of platelet aggregation, cytotoxicity, haemolysis,
      apoptosis and haemorrhage. An L-amino-acid oxidase from Lachesis muta venom has
      been purified and crystallized. The crystals belonged to space group P21, with
      unit-cell parameters a=66.05, b=79.41, c=100.52 A, beta=96.55 degrees . The
      asymmetric unit contained two molecules and the structure has been determined and
      partially refined at 3.0 A resolution.

PMID- 25372832
TI  - Crystallization and preliminary X-ray diffraction analysis of the S
      adenosylhomocysteine hydrolase (SAHH) from Thermotoga maritima.
AB  - S-Adenosylhomocysteine hydrolase (SAHH) catalyzes the reversible conversion of S
      adenosylhomocysteine into adenosine and homocysteine. The SAHH from Thermotoga
      maritima (TmSAHH) was expressed in Escherichia coli and the recombinant protein
      was purified and crystallized. TmSAHH crystals belonging to space group C2, with
      unit-cell parameters a=106.3, b=112.0, c=164.9 A, beta=103.5 degrees , were
      obtained by the sitting-drop vapour-diffusion method and diffracted to 2.85 A
      resolution. Initial phase determination by molecular replacement clearly
      indicated that the crystal contains one homotetramer per asymmetric unit. Further
      refinement of the crystal structure is in progress.

PMID- 25372833
TI  - Cloning, expression, purification, crystallization and X-ray crystallographic
      analysis of PhaA from Ralstonia eutropha.
AB  - Polyhydroxybutyrate (PHB) is a biopolymer that is in the spotlight because of its
      broad applications in bioplastics, fine chemicals, implant biomaterials and
      biofuels. PhaA from Ralstonia eutropha (RePhaA) is the first enzyme in the PHB
      biosynthetic pathway and catalyzes the condensation reaction of two acetyl-CoA
      molecules to give acetoacetyl-CoA. RePhaA was crystallized using the hanging-drop
      vapour-diffusion method in the presence of 20% polyethylene glycol monomethyl
      ether 2K, 0.1 M Tris-HCl pH 8.5 and 0.2 M trimethylamine N-oxide dihydrate at 295
      K. X-ray diffraction data were collected to a maximum resolution of 1.96 A on a
      synchrotron beamline. The crystal belonged to space group P21, with unit-cell
      parameters a=68.38, b=105.47, c=106.91 A, alpha=gamma=90, beta=106.18 degrees .
      With four subunits per asymmetric unit, the crystal volume per unit protein
      weight (VM) is 2.3 A3 Da(-1), which corresponds to a solvent content of
      approximately 46.2%. The structure was solved by the molecular-replacement method
      and refinement of the structure is in progress.

PMID- 25372834
TI  - Crystallization, room-temperature X-ray diffraction and preliminary analysis of
      Kaposi's sarcoma herpesvirus LANA bound to DNA.
AB  - The latency-associated nuclear antigen (LANA) is the latent origin-binding
      protein and chromatin anchor of the Kaposi's sarcoma herpesvirus (KSHV/HHV-8)
      genome. Its C-terminal domain (CTD) binds sequence-specifically to the viral
      origin of replication, whereas the N-terminal domain links it to nucleosomes of
      cellular chromatin for long-term persistence in dividing host cells. Here, the
      crystallization and X-ray data acquisition of a mutant LANA CTD in complex with
      its wild-type target DNA LBS1 is described. This report describes the rational
      protein engineering for successful co-crystallization with DNA and X-ray
      diffraction data collection at room temperature on the high-brilliance third
      generation synchrotron PETRA III at DESY, Germany. 

PMID- 25372835
TI  - Genetic susceptibility, colony size, and water temperature drive white-pox
      disease on the coral Acropora palmata.
AB  - Outbreaks of coral diseases are one of the greatest threats to reef corals in the
      Caribbean, yet the mechanisms that lead to coral diseases are still largely
      unknown. Here we examined the spatial-temporal dynamics of white-pox disease on
      Acropora palmata coral colonies of known genotypes. We took a Bayesian approach,
      using Integrated Nested Laplace Approximation algorithms, to examine which
      covariates influenced the presence of white-pox disease over seven years. We
      showed that colony size, genetic susceptibility of the coral host, and high-water
      temperatures were the primary tested variables that were positively associated
      with the presence of white-pox disease on A. palmata colonies. Our study also
      showed that neither distance from previously diseased individuals, nor colony
      location, influenced the dynamics of white-pox disease. These results suggest
      that white-pox disease was most likely a consequence of anomalously high water
      temperatures that selectively compromised the oldest colonies and the most
      susceptible coral genotypes. 

PMID- 25372836
TI  - The application of Gaussian mixture models for signal quantification in MALDI-TOF
      mass spectrometry of peptides.
AB  - Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) coupled
      with stable isotope standards (SIS) has been used to quantify native peptides.
      This peptide quantification by MALDI-TOF approach has difficulties quantifying
      samples containing peptides with ion currents in overlapping spectra. In these
      overlapping spectra the currents sum together, which modify the peak heights and
      make normal SIS estimation problematic. An approach using Gaussian mixtures based
      on known physical constants to model the isotopic cluster of a known compound is
      proposed here. The characteristics of this approach are examined for single and
      overlapping compounds. The approach is compared to two commonly used SIS
      quantification methods for single compound, namely Peak Intensity method and
      Riemann sum area under the curve (AUC) method. For studying the characteristics
      of the Gaussian mixture method, Angiotensin II, Angiotensin-2-10, and Angiotenisn
      1-9 and their associated SIS peptides were used. The findings suggest, Gaussian
      mixture method has similar characteristics as the two methods compared for
      estimating the quantity of isolated isotopic clusters for single compounds. All
      three methods were tested using MALDI-TOF mass spectra collected for peptides of
      the renin-angiotensin system. The Gaussian mixture method accurately estimated
      the native to labeled ratio of several isolated angiotensin peptides (5.2% error
      in ratio estimation) with similar estimation errors to those calculated using
      peak intensity and Riemann sum AUC methods (5.9% and 7.7%, respectively). For
      overlapping angiotensin peptides, (where the other two methods are not
      applicable) the estimation error of the Gaussian mixture was 6.8%, which is
      within the acceptable range. In summary, for single compounds the Gaussian
      mixture method is equivalent or marginally superior compared to the existing
      methods of peptide quantification and is capable of quantifying overlapping
      (convolved) peptides within the acceptable margin of error. 

PMID- 25372837
TI  - Socioeconomic disparity in survival after breast cancer in ireland: observational
      study.
AB  - We evaluated the relationship between breast cancer survival and deprivation
      using data from the Irish National Cancer Registry. Cause-specific survival was
      compared between five area-based socioeconomic deprivation strata using Cox
      regression. Patient and tumour characteristics and treatment were compared using
      modified Poisson regression with robust variance estimation. Based on 21356
      patients diagnosed 1999-2008, age-standardized five-year survival averaged 80% in
      the least deprived and 75% in the most deprived stratum. Age-adjusted mortality
      risk was 33% higher in the most deprived group (hazard ratio 1.33, 95% CI 1.21
      1.45, P<0.001). The most deprived groups were more likely to present with
      advanced stage, high grade or hormone receptor-negative cancer, symptomatically,
      or with significant comorbidity, and to be smokers or unmarried, and less likely
      to have breast-conserving surgery. Cox modelling suggested that the available
      data on patient, tumour and treatment factors could account for only about half
      of the survival disparity (adjusted hazard ratio 1.18, 95% CI 0.97-1.43, P =
      0.093). Survival disparity did not diminish over time, compared with the period
      1994-1998. Persistent survival disparities among Irish breast cancer patients
      suggest unequal use of or access to services and highlight the need for further
      research to understand and remove the behavioural or other barriers involved. 

PMID- 25372838
TI  - Array-based comparative genomic hybridization analysis reveals chromosomal copy
      number aberrations associated with clinical outcome in canine diffuse large B
      cell lymphoma.
AB  - Canine Diffuse Large B-cell Lymphoma (cDLBCL) is an aggressive cancer with
      variable clinical response. Despite recent attempts by gene expression profiling
      to identify the dog as a potential animal model for human DLBCL, this tumor
      remains biologically heterogeneous with no prognostic biomarkers to predict
      prognosis. The aim of this work was to identify copy number aberrations (CNAs) by
      high-resolution array comparative genomic hybridization (aCGH) in 12 dogs with
      newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end
      of therapy and at relapse were also assessed. In primary DLBCLs, 90 different
      genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains
      in chr13 were significantly correlated with clinical stage. In addition, specific
      regions of gains and losses were significantly associated to duration of
      remission. In primary DLBCLs, individual variability was found, however 14
      recurrent CNAs (>30%) were identified. Losses involving IGK, IGL and IGH were
      always found, and gains along the length of chr13 and chr31 were often observed
      (>41%). In these segments, MYC, LDHB, HSF1, KIT and PDGFRalpha are annotated. At
      the end of therapy, dogs in remission showed four new CNAs, whereas three new
      CNAs were observed in dogs at relapse compared with the previous profiles. One ex
      novo CNA, involving TCR, was present in dogs in remission after therapy, possibly
      induced by the autologous vaccine. Overall, aCGH identified small CNAs associated
      with outcome, which, along with future expression studies, may reveal target
      genes relevant to cDLBCL. 

PMID- 25372839
TI  - Isolation and characterization of marine Brevibacillus sp. S-1 collected from
      South China Sea and a novel antitumor peptide produced by the strain.
AB  - A Gram-positive, rod-shaped bacterium, designated as S-1, was isolated from a
      marine sediment sample collected from South China Sea. Phylogenetic analysis
      based on 16S rRNA gene sequence showed that S-1 belongs to the genus
      Brevibacillus. A novel cytotoxic peptide was isolated from the fermentation broth
      of the marine-derived bacterium Brevibacillus sp. S-1, using ion-exchange
      chromatography and reverse-phase HPLC chromatography. The molecular weight of
      this peptide was determined as 1570 Da by MALDI-TOF mass spectrometry, and its
      structure was proposed as a cyclic peptide elucidated by MALDI-TOF/TOF mass
      spectrometry and de novo sequencing. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H
      tetrazolium bromide (MTT) assay showed that this peptide exhibited cytotoxicity
      against BEL-7402 human hepatocellular carcinoma cells, RKO human colon carcinoma
      cells, A549 human lung carcinoma cells, U251 human glioma cells and MCF-7 human
      breast carcinoma cells. Additionally, SBP exhibited low cytotoxicity against HFL1
      human normal fibroblast lung cells. The result suggested that the cytotoxic
      effect of the peptide is specific to tumor cells. 

PMID- 25372841
TI  - Multiple-fingerprint analysis for investigating quality control of Flammulina
      velutipes fruiting body polysaccharides.
AB  - Quality control issues overshadow potential health benefits of the edible
      mushroom Flammulina velutipes, with the detection and isolation of
      polysaccharides posing particular problems. In this study, multiple-fingerprint
      analysis was performed using chemometrics to assess polysaccharide quality and
      antioxidant activity of F. velutipes fruiting bodies from different sources. The
      authentic source exhibited differences in both oxygen radical absorbance capacity
      and ferric reducing antioxidant power from foreign sources. IR spectroscopic/HPLC
      fingerprints of polysaccharide extracts from the authentic source were
      established and applied to assess the polysaccharide quality of foreign sources.
      Analysis of IR fingerprints using Pearson correlation coefficient gave
      correlation coefficient r values of 0.788 and 0.828 for two foreign sources,
      respectively, indicating distinctness from the authentic source. Analysis of HPLC
      fingerprints using the supervised method by Traditional Chinese Medicine could
      not discriminate between sources (r > 0.9), but principal component analysis of
      IR and HPLC fingerprints distinguished the foreign sources. 

PMID- 25372840
TI  - The reversal effects of 3-bromopyruvate on multidrug resistance in vitro and in
      vivo derived from human breast MCF-7/ADR cells.
AB  - PURPOSE: P-glycoprotein mediated efflux is one of the main mechanisms for
      multidrug resistance in cancers, and 3-Bromopyruvate acts as a promising
      multidrug resistance reversal compound in our study. To test the ability of 3
      Bromopyruvate to overcome P-glycoprotein-mediated multidrug resistance and to
      explore its mechanisms of multidrug resistance reversal in MCF-7/ADR cells, we
      evaluate the in vitro and in vivo modulatory activity of this compound. METHODS:
      The in vitro and in vivo activity was determined using the MTT assay and human
      breast cancer xenograft models. The gene and protein expression of P-glycoprotein
      were determined using real-time polymerase chain reaction and the Western
      blotting technique, respectively. ABCB-1 bioactivity was tested by fluorescence
      microscopy, multi-mode microplate reader, and flow cytometry. The intracellular
      levels of ATP, HK-II, and ATPase activity were based on an assay kit according to
      the manufacturer's instructions. RESULTS: 3-Bromopyruvate treatment led to marked
      decreases in the IC50 values of selected chemotherapeutic drugs [e.g.,
      doxorubicin (283 folds), paclitaxel (85 folds), daunorubicin (201 folds), and
      epirubicin (171 folds)] in MCF-7/ADR cells. 3-Bromopyruvate was found also to
      potentiate significantly the antitumor activity of epirubicin against MCF-7/ADR
      xenografts. The intracellular level of ATP decreased 44%, 46% in the presence of
      12.5.25 uM 3-Bromopyruvate, whereas the accumulation of rhodamine 123 and
      epirubicin (two typical P-glycoprotein substrates) in cells was significantly
      increased. Furthermore, we found that the mRNA and the total protein level of P
      glycoprotein were slightly altered by 3-Bromopyruvate. Moreover, the ATPase
      activity was significantly inhibited when 3-Bromopyruvate was applied.
      CONCLUSION: We demonstrated that 3-Bromopyruvate can reverse P-glycoprotein
      mediated efflux in MCF-7/ADR cells. Multidrug resistance reversal by 3
      Bromopyruvate occurred through at least three approaches, namely, a decrease in
      the intracellular level of ATP and HK-II bioactivity, the inhibition of ATPase
      activity, and the slight decrease in P-glycoprotein expression in MCF-7/ADR
      cells.

PMID- 25372842
TI  - Self-assembling array of magnetoelectrostatic jets from the surface of a
      superparamagnetic ionic liquid.
AB  - Electrospray is a versatile technology used, for example, to ionize biomolecules
      for mass spectrometry, create nanofibers and nanowires, and propel spacecraft in
      orbit. Traditionally, electrospray is achieved via microfabricated capillary
      needle electrodes that are used to create the fluid jets. Here we report on
      multiple parallel jetting instabilities realized through the application of
      simultaneous electric and magnetic fields to the surface of a superparamagnetic
      electrically conducting ionic liquid with no needle electrodes. The ionic liquid
      ferrofluid is synthesized by suspending magnetic nanoparticles in a room
      temperature molten salt carrier liquid. Two ILFFs are reported: one based on
      ethylammonium nitrate (EAN) and the other based on EMIM-NTf2. The ILFFs display
      an electrical conductivity of 0.63 S/m and a relative magnetic permeability as
      high as 10. When coincident electric and magnetic fields are applied to these
      liquids, the result is a self-assembling array of emitters that are composed
      entirely of the colloidal fluid. An analysis of the magnetic surface stress
      induced on the ILFF shows that the electric field required for transition to
      spray can be reduced by as much as 4.5 * 10(7) V/m compared to purely
      electrostatic spray. Ferrofluid mode studies in nonuniform magnetic fields show
      that it is feasible to realize arrays with up to 16 emitters/mm(2). 

PMID- 25372843
TI  - The application of predictive modelling for determining bio-environmental factors
      affecting the distribution of blackflies (Diptera: Simuliidae) in the Gilgel Gibe
      watershed in Southwest Ethiopia.
AB  - Blackflies are important macroinvertebrate groups from a public health as well as
      ecological point of view. Determining the biological and environmental factors
      favouring or inhibiting the existence of blackflies could facilitate
      biomonitoring of rivers as well as control of disease vectors. The combined use
      of different predictive modelling techniques is known to improve identification
      of presence/absence and abundance of taxa in a given habitat. This approach
      enables better identification of the suitable habitat conditions or environmental
      constraints of a given taxon. Simuliidae larvae are important biological
      indicators as they are abundant in tropical aquatic ecosystems. Some of the
      blackfly groups are also important disease vectors in poor tropical countries.
      Our investigations aim to establish a combination of models able to identify the
      environmental factors and macroinvertebrate organisms that are favourable or
      inhibiting blackfly larvae existence in aquatic ecosystems. The models developed
      using macroinvertebrate predictors showed better performance than those based on
      environmental predictors. The identified environmental and macroinvertebrate
      parameters can be used to determine the distribution of blackflies, which in turn
      can help control river blindness in endemic tropical places. Through a
      combination of modelling techniques, a reliable method has been developed that
      explains environmental and biological relationships with the target organism,
      and, thus, can serve as a decision support tool for ecological management
      strategies. 

PMID- 25372845
TI  - Predicting gaseous reaction rates of short chain chlorinated paraffins with .OH:
      overcoming the difficulty in experimental determination.
AB  - Short chain chlorinated paraffins (SCCPs) are under evaluation for inclusion in
      the Stockholm Convention on persistent organic pollutants. However, information
      on their reaction rate constants with gaseous .OH (kOH) is unavailable, limiting
      the evaluation of their persistence in the atmosphere. Experimental determination
      of kOH is confined by the unavailability of authentic chemical standards for some
      SCCP congeners. In this study, we evaluated and selected density functional
      theory (DFT) methods to predict kOH of SCCPs, by comparing the experimental kOH
      values of six polychlorinated alkanes (PCAs) with those calculated by the
      different theoretical methods. We found that the M06-2X/6-311+G(3df,2pd)//B3LYP/6
      311 +G(d,p) method is time-effective and can be used to predict kOH of PCAs.
      Moreover, based on the calculated kOH of nine SCCPs and available experimental
      kOH values of 22 PCAs with low carbon chain, a quantitative structure-activity
      relationship (QSAR) model was developed. The molecular structural characteristics
      determining the .OH reaction rate were discussed. logkOH was found to negatively
      correlate with the percentage of chlorine substitutions (Cl%). The DFT
      calculation method and the QSAR model are important alternatives to the
      conventional experimental determination of kOH for SCCPs, and are prospective in
      predicting their persistence in the atmosphere. 

PMID- 25372844
TI  - Lymphocyte Activation Gene 3 (LAG-3) modulates the ability of CD4 T-cells to be
      suppressed in vivo.
AB  - Lymphocyte Activation Gene - 3 (LAG-3) is an immune checkpoint molecule that
      regulates both T-cell activation and homeostasis. However, the molecular
      mechanisms underlying LAG-3's function are generally unknown. Using a model in
      which LAG-3 blockade or absence reliably augmented homeostatic proliferation in
      vivo, we found that IL-2 and STAT5 are critical for LAG-3 function. Similarly,
      LAG-3 blockade was ineffective in the absence of regulatory T-cells (Treg),
      suggesting an important role for LAG-3 in either the responsiveness of
      conventional T-cells (Tconv) to regulation, or a relative defect in the ability
      of LAG-3 KO regulatory T-cells (Treg) to suppress the proliferation of Tconv. In
      this model, LAG-3 KO Treg suppressed proliferation in a manner fairly similar to
      wild-type (WT) Treg, but LAG-3 KO Tconv were relatively resistant to suppression.
      Further studies also identified a role for LAG-3 in the induction/expansion of
      Treg. Finally, we found that LAG-3 blockade (or knockout) led to a relative
      skewing of naive CD4 T-cells toward a TH1 phenotype both in vitro and in in vivo.
      Together, these data suggest that LAG-3 expression on Tconv cells makes them more
      susceptible to Treg based suppression, and also regulates the development of a
      TH1 T-cell response. 

PMID- 25372847
TI  - Two new GLP-1 receptor agonists for diabetes.

PMID- 25372846
TI  - Antipsychotic treatment and functional connectivity of the striatum in first
      episode schizophrenia.
AB  - IMPORTANCE: Previous evidence has implicated corticostriatal abnormalities in the
      pathophysiology of psychosis. Although the striatum is the primary target of all
      efficacious antipsychotics, the relationship between its functional connectivity
      and symptomatic reduction remains unknown. OBJECTIVE: To explore the longitudinal
      effect of treatment with second-generation antipsychotics on functional
      connectivity of the striatum during the resting state in patients experiencing a
      first episode of psychosis. DESIGN, SETTING, AND PARTICIPANTS: This prospective
      controlled study took place at a clinical research center and included 24
      patients with first-episode psychosis and 24 healthy participants matched for
      age, sex, education, and handedness. Medications were administered in a double
      blind randomized manner. INTERVENTIONS: Patients were scanned at baseline and
      after 12 weeks of treatment with either risperidone or aripiprazole. Their
      symptoms were evaluated with the Brief Psychiatric Rating Scale at baseline and
      follow-up. Healthy participants were scanned twice within a 12-week interval.
      MAIN OUTCOMES AND MEASURES: Functional connectivity of striatal regions was
      examined via functional magnetic resonance imaging using a seed-based approach.
      Changes in functional connectivity of these seeds were compared with reductions
      in ratings of psychotic symptoms. RESULTS: Patients had a median exposure of 1
      day to antipsychotic medication prior to being scanned (mean [SD] = 4.5 [6.1]).
      Eleven patients were treated with aripiprazole and 13 patients were treated with
      risperidone. As psychosis improved, we observed an increase in functional
      connectivity between striatal seed regions and the anterior cingulate,
      dorsolateral prefrontal cortex, and limbic regions such as the hippocampus and
      anterior insula (P < .05, corrected for multiple comparisons). Conversely, a
      negative relationship was observed between reduction in psychosis and functional
      connectivity of striatal regions with structures within the parietal lobe (P <
      .05, corrected for multiple comparisons). CONCLUSIONS AND RELEVANCE: Our results
      indicated that corticostriatal functional dysconnectivity in psychosis is a state
      dependent phenomenon. Increased functional connectivity of the striatum with
      prefrontal and limbic regions may be a biomarker for improvement in symptoms
      associated with antipsychotic treatment.

PMID- 25372848
TI  - A combination of ledipasvir and sofosbuvir (Harvoni) for hepatitis C.

PMID- 25372849
TI  - Contrave--a combination of bupropion and naltrexone for weight loss.

PMID- 25372854
TI  - Ebola virus disease in West Africa--clinical manifestations and management.

PMID- 25372855
TI  - Evaluating Alternative Risk Adjusters for Medicare.
AB  - In this study the authors use 3 years of the Medicare Current Beneficiary Survey
      (MCBS) to evaluate alternative demographic, survey, and claims-based risk
      adjusters for Medicare capitation payment. The survey health-status models have
      three to four times the predictive power of the demographic models. The risk
      adjustment model derived from claims diagnoses has 75-percent greater predictive
      power than a comprehensive survey model. No single model predicts average
      expenditures well for all beneficiary subgroups of interest, suggesting a
      combined model may be appropriate. More data are needed to obtain stable
      estimates of model parameters. Advantages and disadvantages of alternative risk
      adjusters are discussed.

PMID- 25372853
TI  - The same microbiota and a potentially discriminant metabolome in the saliva of
      omnivore, ovo-lacto-vegetarian and Vegan individuals.
AB  - The salivary microbiota has been linked to both oral and non-oral diseases. Scant
      knowledge is available on the effect of environmental factors such as long-term
      dietary choices on the salivary microbiota and metabolome. This study analyzed
      the microbial diversity and metabolomic profiles of the saliva of 161 healthy
      individuals who followed an omnivore or ovo-lacto-vegetarian or vegan diet. A
      large core microbiota was identified, including 12 bacterial genera, found in
      >98% of the individuals. The subjects could be stratified into three "salivary
      types" that differed on the basis of the relative abundance of the core genera
      Prevotella, Streptococcus/Gemella and Fusobacterium/Neisseria. Statistical
      analysis indicated no effect of dietary habit on the salivary microbiota.
      Phylogenetic beta-diversity analysis consistently showed no differences between
      omnivore, ovo-lacto-vegetarian and vegan individuals. Metabolomic profiling of
      saliva using (1)H-NMR and GC-MS/SPME identified diet-related biomarkers that
      enabled a significant discrimination between the 3 groups of individuals on the
      basis of their diet. Formate, urea, uridine and 5-methyl-3-hexanone could
      discriminate samples from omnivores, whereas 1-propanol, hexanoic acid and
      proline were characteristic of non-omnivore diets. Although the salivary
      metabolome can be discriminating for diet, the microbiota has a remarkable inter
      individual stability and did not vary with dietary habits. Microbial homeostasis
      might be perturbed with sub-standard oral hygiene or other environmental factors,
      but there is no current indication that a choice of an omnivore, ovo-lacto
      vegetarian or vegan diet can lead to a specific composition of the oral
      microbiota with consequences on the oral homeostasis.

PMID- 25372856
TI  - Ant colonies prefer infected over uninfected nest sites.
AB  - During colony relocation, the selection of a new nest involves exploration and
      assessment of potential sites followed by colony movement on the basis of a
      collective decision making process. Hygiene and pathogen load of the potential
      nest sites are factors worker scouts might evaluate, given the high risk of
      epidemics in group-living animals. Choosing nest sites free of pathogens is
      hypothesized to be highly efficient in invasive ants as each of their introduced
      populations is often an open network of nests exchanging individuals
      (unicolonial) with frequent relocation into new nest sites and low genetic
      diversity, likely making these species particularly vulnerable to parasites and
      diseases. We investigated the nest site preference of the invasive pharaoh ant,
      Monomorium pharaonis, through binary choice tests between three nest types: nests
      containing dead nestmates overgrown with sporulating mycelium of the
      entomopathogenic fungus Metarhizium brunneum (infected nests), nests containing
      nestmates killed by freezing (uninfected nests), and empty nests. In contrast to
      the expectation pharaoh ant colonies preferentially (84%) moved into the infected
      nest when presented with the choice of an infected and an uninfected nest. The
      ants had an intermediate preference for empty nests. Pharaoh ants display an
      overall preference for infected nests during colony relocation. While we cannot
      rule out that the ants are actually manipulated by the pathogen, we propose that
      this preference might be an adaptive strategy by the host to "immunize" the
      colony against future exposure to the same pathogenic fungus. 

PMID- 25372858
TI  - Contact angles of surfactant solutions on heterogeneous surfaces.
AB  - Using Gibbs' adsorption equation and a literature isotherm, a new general model
      to predict the contact angle of surfactant solutions on (smooth or rough)
      chemically heterogeneous surfaces is constructed based on the Cassie equation.
      The model allows for adsorption at the liquid-vapor, solid-liquid, and solid
      vapor interfaces. Solid-vapor adsorption is allowed in order to model the
      autophobic effect on hydrophilic surfaces. Using representative values for the
      coefficients which describe adsorption at each interface, model predictions for
      contact angles as a function of f parameters (area fractions) and surfactant
      concentration are made for heterogeneous surfaces made up of different materials.
      On smooth surfaces, the f parameters serve as weighting factors determining how
      to combine the effects of surfactant adsorption on each material to predict the
      behavior on the heterogeneous surface. Due to the non-linear nature of the model,
      the inclusion of a small amount of hydrophobic material has a greater effect on a
      predominantly hydrophilic material than vice versa, explaining the result seen in
      literature that a small amount of hydrophobic contamination (such as oil)
      significantly increases contact angle on a hydrophilic surface. The fact that
      even a small amount of heterogeneity can greatly change experimental results
      could lead to incorrect experimental conclusions about surfactant adsorption if a
      surface were wrongly assumed to be homogeneous. Model predictions rapidly become
      more complex as the number of differently wettable materials present on the
      surface increases. Also, an approximately equal weighting of different materials
      generally leads to more complex behaviors compared to heterogeneous surfaces
      composed largely of a single material. Rough heterogeneous surfaces follow
      previous results for surfactant wetting of rough homogeneous surfaces, leading to
      an amplification/attenuation of surfactant effects for penetrated/unpenetrated
      wetting, and further increasing the complexity of predictions. These potential
      complexities point to the importance of characterizing the heterogeneities of any
      surface under consideration. With proper characterization, the model described in
      this paper will allow for prediction of contact angles on all types of
      heterogeneous surfaces, and design of surfaces for specific interactions with
      surfactant solutions. 

PMID- 25372857
TI  - Ionic electroactive polymer artificial muscles in space applications.
AB  - A large-scale effort was carried out to test the performance of seven types of
      ionic electroactive polymer (IEAP) actuators in space-hazardous environmental
      factors in laboratory conditions. The results substantiate that the IEAP
      materials are tolerant to long-term freezing and vacuum environments as well as
      ionizing Gamma-, X-ray, and UV radiation at the levels corresponding to low Earth
      orbit (LEO) conditions. The main aim of this material behaviour investigation is
      to understand and predict device service time for prolonged exposure to space
      environment. 

PMID- 25372861
TI  - Politics of Health Policy: Yesterday and Today.
AB  - This executive summary of Judith Miller Jones' remarks was prepared by Julie
      Snyder of the University of Texas LBJ School of Public Affairs. The remarks were
      given in the context of a panel presentation moderated by Jones, entitled
      "Politics of Health Policy: Yesterday and Today."

PMID- 25372863
TI  - Treatment results in the different surgery of intradural extramedullary tumor of
      122 cases.
AB  - STUDY DESIGN: A retrospective study of intradural extramedullary tumor.
      OBJECTIVE: To compare the treatment results in the different surgeries of spinal
      intradural extramedullary tumor. METHODS: The study retrospectively reviewed 122
      patients. The minimally invasive surgery (MIS) group was divided into Group A
      (hemilaminectomy + tumor microscopic excision) and Group B (laminectomy + tumor
      microscopic excision + pedicle screw fixation). Meanwhile, the non-MIS group was
      divided into Group C (hemilaminectomy + tumor excision), Group D (laminectomy +
      tumor excision), and Group E (laminectomy + tumor excision + pedicle screw
      fixation). In order to study postoperative spinal stability, we simultaneously
      divided all of the subjects into three categories, namely Group HE:
      hemilaminectomy + tumor excision; Group LE: laminectomy + tumor excision; and
      Group LEPSF: laminectomy + tumor excision + pedicle screw fixation. RESULTS: The
      MIS group exhibited fewer postoperative complications (p<0.05), better short-term
      clinical efficacy (p<0.05) and less non-surgical cost (p<0.05) than in non-MIS
      group. The rate of postoperative spinal instability in hemilaminectomy was lower
      than in laminectomy in a single spinal segment (p<0.05). The rate of
      postoperative spinal instability in laminectomy + pedicle screw fixation was
      lower than in hemilaminectomy and laminectomy in two or more spinal segments
      (p<0.05). CONCLUSION: In the case of appropriate surgical indications, minimally
      invasive surgery for intradural extramedullary tumor is a useful method that can
      successfully produce good clinical results and reduce non-surgical cost. In
      addition, pedicle screw fixation helps avoid spinal postoperative instability.

PMID- 25372862
TI  - Early-life exposure to polycyclic aromatic hydrocarbons and ADHD behavior
      problems.
AB  - IMPORTANCE: Polycyclic aromatic hydrocarbons are widespread urban air pollutants
      from combustion of fossil fuel and other organic material shown previously to be
      neurotoxic. OBJECTIVE: In a prospective cohort study, we evaluated the
      relationship between Attention Deficit Hyperactivity Disorder behavior problems
      and prenatal polycyclic aromatic hydrocarbon exposure, adjusting for postnatal
      exposure. MATERIALS AND METHODS: Children of nonsmoking African-American and
      Dominican women in New York City were followed from in utero to 9 years. Prenatal
      polycyclic aromatic hydrocarbon exposure was estimated by levels of polycyclic
      aromatic hydrocarbon- DNA adducts in maternal and cord blood collected at
      delivery. Postnatal exposure was estimated by the concentration of urinary
      polycyclic aromatic hydrocarbon metabolites at ages 3 or 5. Attention Deficit
      Hyperactivity Disorder behavior problems were assessed using the Child Behavior
      Checklist and the Conners Parent Rating Scale- Revised. RESULTS: High prenatal
      adduct exposure, measured by elevated maternal adducts was significantly
      associated with all Conners Parent Rating Scale-Revised subscales when the raw
      scores were analyzed continuously (N = 233). After dichotomizing at the threshold
      for moderately to markedly atypical symptoms, high maternal adducts were
      significantly associated with the Conners Parent Rating Scale-Revised DSM-IV
      Inattentive (OR = 5.06, 95% CI [1.43, 17.93]) and DSM-IV Total (OR = 3.37, 95% CI
      [1.10, 10.34]) subscales. High maternal adducts were positivity associated with
      the DSM-oriented Attention Deficit/Hyperactivity Problems scale on the Child
      Behavior Checklist, albeit not significant. In the smaller sample with cord
      adducts, the associations between outcomes and high cord adduct exposure were not
      statistically significant (N = 162). CONCLUSION: The results suggest that
      exposure to polycyclic aromatic hydrocarbons encountered in New York City air may
      play a role in childhood Attention Deficit Hyperactivity Disorder behavior
      problems.

PMID- 25372864
TI  - Gun possession among American youth: a discovery-based approach to understand gun
      violence.
AB  - OBJECTIVE: To apply discovery-based computational methods to nationally
      representative data from the Centers for Disease Control and Preventions' Youth
      Risk Behavior Surveillance System to better understand and visualize the
      behavioral factors associated with gun possession among adolescent youth.
      RESULTS: Our study uncovered the multidimensional nature of gun possession across
      nearly five million unique data points over a ten year period (2001-2011).
      Specifically, we automated odds ratio calculations for 55 risk behaviors to
      assemble a comprehensive table of associations for every behavior combination.
      Downstream analyses included the hierarchical clustering of risk behaviors based
      on their association "fingerprint" to 1) visualize and assess which behaviors
      frequently co-occur and 2) evaluate which risk behaviors are consistently found
      to be associated with gun possession. From these analyses, we identified more
      than 40 behavioral factors, including heroin use, using snuff on school property,
      having been injured in a fight, and having been a victim of sexual violence, that
      have and continue to be strongly associated with gun possession. Additionally, we
      identified six behavioral clusters based on association similarities: 1) physical
      activity and nutrition; 2) disordered eating, suicide and sexual violence; 3)
      weapon carrying and physical safety; 4) alcohol, marijuana and cigarette use; 5)
      drug use on school property and 6) overall drug use. CONCLUSIONS: Use of
      computational methodologies identified multiple risk behaviors, beyond more
      commonly discussed indicators of poor mental health, that are associated with gun
      possession among youth. Implications for prevention efforts and future
      interdisciplinary work applying computational methods to behavioral science data
      are described.

PMID- 25372865
TI  - Engineering charge injection interfaces in hybrid light-emitting electrochemical
      cells.
AB  - Light-emitting electrochemical cells (LECs) consists of a thin film of an ionic
      organic semiconductor sandwiched between two electrodes. Because of the large
      density of ions, LECs are often reported to perform independently on the
      electrodes work function. Here we use metal oxides as charge injection layers and
      demonstrate that, although electroluminescence is observed independently of the
      electrodes used, the device performances are strongly dependent on the choice of
      the interface materials. Relying on metal oxide charge injection layers, such
      hybrid devices are of interest for real lighting applications and could pave the
      way for new efficient, stable, low-cost lighting sources. 

PMID- 25372866
TI  - Demonstrations and Designs of Alternative Reimbursement Methods for Home Health
      Services.
AB  - The following summary is of a report from the Secretary of Health and Human
      Services released to Congress on January 19, 1989.

PMID- 25372868
TI  - Nursing Home Initiative.
AB  - Currently, 1.6 million elderly and disabled people receive care in about 17,000
      nursing homes across the United States. In 1987, Congress passed major nursing
      home reforms that defined the role of the State survey and certification process
      in determining the compliance of nursing homes with Federal standards. In 1998,
      the President announced new steps to increase Federal oversight of nursing homes'
      performance, including enhanced monitoring of poorly performing homes, collection
      of new fines from non-compliant homes, and an increased focus on special care
      areas such as nutrition, pressure sores, and abuse. HCFA responded with the
      Nursing Home Initiative (NHI), which was intended to improve the quality of care
      for nursing home residents. Many of the new activities from the NHI have already
      been implemented, but it will take more time before we have all of them fully in
      operation.

PMID- 25372869
TI  - Genome-wide association mapping for kernel and malting quality traits using
      historical European barley records.
AB  - Malting quality is an important trait in breeding barley (Hordeum vulgare L.). It
      requires elaborate, expensive phenotyping, which involves micro-malting
      experiments. Although there is abundant historical information available for
      different cultivars in different years and trials, that historical information is
      not often used in genetic analyses. This study aimed to exploit historical
      records to assist in identifying genomic regions that affect malting and kernel
      quality traits in barley. This genome-wide association study utilized information
      on grain yield and 18 quality traits accumulated over 25 years on 174 European
      spring and winter barley cultivars combined with diversity array technology
      markers. Marker-trait associations were tested with a mixed linear model. This
      model took into account the genetic relatedness between cultivars based on
      principal components scores obtained from marker information. We detected 140
      marker-trait associations. Some of these associations confirmed previously known
      quantitative trait loci for malting quality (on chromosomes 1H, 2H, and 5H).
      Other associations were reported for the first time in this study. The genetic
      correlations between traits are discussed in relation to the chromosomal regions
      associated with the different traits. This approach is expected to be
      particularly useful when designing strategies for multiple trait improvements. 

PMID- 25372870
TI  - Molecular profiling of the Phytophthora plurivora secretome: a step towards
      understanding the cross-talk between plant pathogenic oomycetes and their hosts.
AB  - The understanding of molecular mechanisms underlying host-pathogen interactions
      in plant diseases is of crucial importance to gain insights on different
      virulence strategies of pathogens and unravel their role in plant immunity. Among
      plant pathogens, Phytophthora species are eliciting a growing interest for their
      considerable economical and environmental impact. Plant infection by Phytophthora
      phytopathogens is a complex process coordinated by a plethora of extracellular
      signals secreted by both host plants and pathogens. The characterization of the
      repertoire of effectors secreted by oomycetes has become an active area of
      research for deciphering molecular mechanisms responsible for host plants
      colonization and infection. Putative secreted proteins by Phytophthora species
      have been catalogued by applying high-throughput genome-based strategies and
      bioinformatic approaches. However, a comprehensive analysis of the effective
      secretome profile of Phytophthora is still lacking. Here, we report the first
      large-scale profiling of P. plurivora secretome using a shotgun LC-MS/MS
      strategy. To gain insight on the molecular signals underlying the cross-talk
      between plant pathogenic oomycetes and their host plants, we also investigate the
      quantitative changes of secreted protein following interaction of P. plurivora
      with the root exudate of Fagus sylvatica which is highly susceptible to the root
      pathogen. We show that besides known effectors, the expression and/or secretion
      levels of cell-wall-degrading enzymes were altered following the interaction with
      the host plant root exudate. In addition, a characterization of the F. sylvatica
      root exudate was performed by NMR and amino acid analysis, allowing the
      identification of the main released low-molecular weight components, including
      organic acids and free amino acids. This study provides important insights for
      deciphering the extracellular network involved in the highly susceptible P.
      plurivora-F. sylvatica interaction. 

PMID- 25372871
TI  - Characterization and expression analysis of microRNAs in the tube foot of sea
      cucumber Apostichopus japonicus.
AB  - MicroRNAs (miRNAs) are a class of endogenous non-coding small RNA with average
      length of 22 nucleotides, participating in the post-transcriptional regulation of
      gene expression. In this study, we report the identification and characterization
      of miRNAs in the tube foot of sea cucumber (Apostichopus japonicus) by next
      generation sequencing with Illumina HiSeq 2000 platform. Through the
      bioinformatic analysis, we identified 260 conserved miRNAs and six novel miRNAs
      from the tube foot small RNA transcriptome. Quantitative realtime PCR (qRT-PCR)
      was performed to characterize the specific expression in the tube foot. The
      results indicated that four miRNAs, including miR-29a, miR-29b, miR-2005 and miR
      278-3p, were significantly up-regulated in the tube foot. The target genes of the
      four specifically expressed miRNAs were predicted in silico and validated by
      performing qRT-PCR. Gene ontology (GO) and KEGG pathway analyses with the target
      genes of these four miRNAs were conducted to further understand the regulatory
      function in the tube foot. This is the first study to profile the miRNA
      transcriptome of the tube foot in sea cucumber. This work will provide valuable
      genomic resources to understand the mechanisms of gene regulation in the tube
      foot, and will be useful to assist the molecular breeding in sea cucumber. 

PMID- 25372874
TI  - Acceptance of brain-computer interfaces in amyotrophic lateral sclerosis.
AB  - Brain-computer interfaces (BCI) have the potential to permit patients with
      amyotrophic lateral sclerosis (ALS) to communicate even when locked in. Although
      as many as half of patients with ALS develop cognitive or behavioral dysfunction,
      the impact of these factors on acceptance of and ability to use a BCI has not
      been studied. We surveyed patients with ALS and their caregivers about BCIs used
      as assistive communication tools. The survey focused on the features of a BCI
      system, the desired end-use functions, and requirements. Functional, cognitive,
      and behavioral data were collected from patients and analyzed for their influence
      over decisions about BCI device use. Results showed that behavioral impairment
      was associated with decreased receptivity to the use of BCI technology. In
      addition, the operation of a BCI system during a pilot study altered patients'
      opinions of the utility of the system, generally in line with their perceived
      performance at controlling the device. In conclusion, these two findings have
      implications for the engineering design and clinical care phases of assistive
      device deployment. 

PMID- 25372873
TI  - Prevalence of veterinary antibiotics and antibiotic-resistant Escherichia coli in
      the surface water of a livestock production region in northern China.
AB  - This study investigated the occurrence of 12 veterinary antibiotics (VAs) and the
      susceptibility of Escherichia coli (E. coli) in a rural water system that was
      affected by livestock production in northern China. Each of the surveyed sites
      was determined with at least eight antibiotics with maximum concentration of up
      to 450 ng L(-1). The use of VAs in livestock farming probably was a primary
      source of antibiotics in the rivers. Increasing total antibiotics were measured
      from up- to mid- and downstream in the two tributaries. Eighty-eight percent of
      the 218 E. coli isolates that were derived from the study area exhibited, in
      total, 48 resistance profiles against the eight examined drugs. Significant
      correlations were found among the resistance rates of sulfamethoxazole
      trimethoprim, chloromycetin and ampicillin as well as between tetracycline and
      chlortetracycline, suggesting a possible cross-selection for resistance among
      these drugs. The E. coli resistance frequency also increased from up- to
      midstream in the three rivers. E. coli isolates from different water systems
      showed varying drug numbers of resistance. No clear relationship was observed in
      the antibiotic resistance frequency with corresponding antibiotic concentration,
      indicating that the antibiotic resistance for E. coli in the aquatic environment
      might be affected by factors besides antibiotics. High numbers of resistant E.
      coli were also isolated from the conserved reservoir. These results suggest that
      rural surface water may become a large pool of VAs and resistant bacteria. This
      study contributes to current information on VAs and resistant bacteria
      contamination in aquatic environments particularly in areas under intensive
      agriculture. Moreover, this study indicates an urgent need to monitor the use of
      VAs in animal production, and to control the release of animal-originated
      antibiotics into the environment.

PMID- 25372872
TI  - Sexual dimorphism in the human olfactory bulb: females have more neurons and
      glial cells than males.
AB  - Sex differences in the human olfactory function reportedly exist for olfactory
      sensitivity, odorant identification and memory, and tasks in which odors are
      rated based on psychological features such as familiarity, intensity,
      pleasantness, and others. Which might be the neural bases for these behavioral
      differences? The number of cells in olfactory regions, and especially the number
      of neurons, may represent a more accurate indicator of the neural machinery than
      volume or weight, but besides gross volume measures of the human olfactory bulb,
      no systematic study of sex differences in the absolute number of cells has yet
      been undertaken. In this work, we investigate a possible sexual dimorphism in the
      olfactory bulb, by quantifying postmortem material from 7 men and 11 women (ages
      55-94 years) with the isotropic fractionator, an unbiased and accurate method to
      estimate absolute cell numbers in brain regions. Female bulbs weighed 0.132 g in
      average, while male bulbs weighed 0.137 g, a non-significant difference; however,
      the total number of cells was 16.2 million in females, and 9.2 million in males,
      a significant difference of 43.2%. The number of neurons in females reached 6.9
      million, being no more than 3.5 million in males, a difference of 49.3%. The
      number of non-neuronal cells also proved higher in women than in men: 9.3 million
      and 5.7 million, respectively, a significant difference of 38.7%. The same
      differences remained when corrected for mass. Results demonstrate a sex-related
      difference in the absolute number of total, neuronal and non-neuronal cells,
      favoring women by 40-50%. It is conceivable that these differences in
      quantitative cellularity may have functional impact, albeit difficult to infer
      how exactly this would be, without knowing the specific circuits cells make.
      However, the reported advantage of women as compared to men may stimulate future
      work on sex dimorphism of synaptic microcircuitry in the olfactory bulb. 

PMID- 25372875
TI  - The ratio of circulating regulatory T cells (Tregs)/Th17 cells is associated with
      acute allograft rejection in liver transplantation.
AB  - CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) and Th17 cells are known to be
      involved in the alloreactive responses in organ transplantation, but little is
      known about the relationship between Tregs and Th17 cells in the context of liver
      alloresponse. Here, we investigated whether the circulating Tregs/Th17 ratio is
      associated with acute allograft rejection in liver transplantation. In present
      study, thirty-eight patients who received liver transplant were enrolled. The
      patients were divided into two groups: acute allograft rejection group (Gr-AR) (n
      = 16) and stable allograft liver function group (Gr-SF) (n = 22). The frequencies
      of circulating Tregs and circulating Th17 cells, as well as Tregs/Th17 ratio were
      determined using flow cytometry. The association between Tregs/Th17 ratio and
      acute allograft rejection was then analyzed. Our results showed that the
      frequency of circulating Tregs was significantly decreased, whereas the frequency
      of circulating Th17 cells was significantly increased in liver allograft
      recipients who developed acute rejection. Tregs/Th17 ratio had a negative
      correlation with liver damage indices and the score of rejection activity index
      (RAI) after liver transplantation. In addition, the percentages of CTLA-4(+), HLA
      DR(+), Ki67(+), and IL-10(+) Tregs were higher in Gr-SF group than in Gr-AR
      group. Our results suggested that the ratio of circulating Tregs/Th17 cells is
      associated with acute allograft rejection, thus the ratio may serve as an
      alternative marker for the diagnosis of acute rejection.

PMID- 25372877
TI  - Rates of Hospitalization for Ambulatory Care Sensitive Conditions in the
      Medicare+Choice Population.
AB  - This article evaluates the feasibility of developing hospitalization rates for
      ambulatory care sensitive conditions (ACSCs) for the Medicare+Choice (M+C)
      population. M+C inpatient encounter data were used to calculate 15 ACSC rates. We
      found the initial reporting year of M+C inpatient encounter data had no apparent
      volume or diagnosis-based biases and over 90 percent of M+C organizations had
      sufficient enrollment to produce statistically reliable rates. Further, our study
      results support the premise that ACSCs could be used as sentinel events for
      potentially vulnerable populations; the oldest old and the disabled experienced
      statistically significant higher rates of ACSC admissions than younger Medicare
      beneficiaries.

PMID- 25372876
TI  - Development and evaluation of 'briefing notes' as a novel knowledge translation
      tool to aid the implementation of sex/gender analysis in systematic reviews: a
      pilot study.
AB  - BACKGROUND: There is increasing recognition of sex/gender differences in health
      and the importance of identifying differential effects of interventions for men
      and women. Yet, to whom the research evidence does or does not apply, with regard
      to sex/gender, is often insufficiently answered. This is also true for systematic
      reviews which synthesize results of primary studies. A lack of analysis and
      reporting of evidence on sex/gender raises concerns about the applicability of
      systematic reviews. To bridge this gap, this pilot study aimed to translate
      knowledge about sex/gender analysis (SGA) into a user-friendly 'briefing note'
      format and evaluate its potential in aiding the implementation of SGA in
      systematic reviews. METHODS: Our Sex/Gender Methods Group used an interactive
      process to translate knowledge about sex/gender into briefing notes, a concise
      communication tool used by policy and decision makers. The briefing notes were
      developed in collaboration with three Cochrane Collaboration review groups
      (HIV/AIDS, Hypertension, and Musculoskeletal) who were also the target knowledge
      users of the briefing notes. Briefing note development was informed by existing
      systematic review checklists, literature on sex/gender, in-person and virtual
      meetings, and consultation with topic experts. Finally, we held a workshop for
      potential users to evaluate the notes. RESULTS: Each briefing note provides
      tailored guidance on considering sex/gender to reviewers who are planning or
      conducting systematic reviews and includes the rationale for considering
      sex/gender, with examples specific to each review group's focus. Review authors
      found that the briefing notes provided welcome guidance on implementing SGA that
      was clear and concise, but also identified conceptual and implementation
      challenges. CONCLUSIONS: Sex/gender briefing notes are a promising knowledge
      translation tool. By encouraging sex/gender analysis and equity considerations in
      systematic reviews, the briefing notes can assist systematic reviewers in
      ensuring the applicability of research evidence, with the goal of improved health
      outcomes for diverse populations.

PMID- 25372878
TI  - Snout shape in extant ruminants.
AB  - Snout shape is a prominent aspect of herbivore feeding ecology, interacting with
      both forage selectivity and intake rate. Previous investigations have suggested
      ruminant feeding styles can be discriminated via snout shape, with grazing and
      browsing species characterised by 'blunt' and 'pointed' snouts respectively,
      often with specification of an 'intermediate' sub-grouping to represent ambiguous
      feeding styles and/or morphologies. Snout shape morphology is analysed here using
      a geometric morphometric approach to compare the two-dimensional profiles of the
      premaxilla in ventral aspect for a large sample of modern ruminant species, for
      which feeding modes are known from secondary criteria. Results suggest that, when
      browsing and grazing ruminants are classified ecologically based on a range of
      feeding style indicators, they cannot be discriminated unambiguously on the basis
      of snout profile shape alone. Profile shapes in our sample form a continuum with
      substantial overlap between groupings and a diverse range of morphologies.
      Nevertheless, we obtained an 83.8 percent ratio of correct post hoc feeding style
      categorisations based on the proximity of projected profile shapes to group
      centroids in the discriminant space. Accordingly, this procedure for identifying
      species whose feeding strategy is 'unknown' can be used with a reasonable degree
      of confidence, especially if backed-up by additional information. Based on these
      results we also refine the definitions of snout shape varieties, taking advantage
      of the descriptive power that geometric morphometrics offers to characterize the
      morphological disparities observed. The shape variance exhibited by both browsing
      and grazing ruminants corresponds strongly to body mass, providing further
      evidence for an interaction between snout shape, feeding style, and body size
      evolution. Finally, by exploring the role of phylogenetic similarity in snout
      shape, we find a slight increase in successful categorisation when repeating the
      analysis with phylogenetic control on the geometric profiles. 

PMID- 25372879
TI  - Stone anvil damage by wild bearded capuchins (Sapajus libidinosus) during
      pounding tool use: a field experiment.
AB  - We recorded the damage that wild bearded capuchin monkeys (Sapajus libidinosus)
      caused to a sandstone anvil during pounding stone tool use, in an experimental
      setting. The anvil was undamaged when set up at the Fazenda Boa Vista (FBV) field
      laboratory in Piaui, Brazil, and subsequently the monkeys indirectly created a
      series of pits and destroyed the anvil surface by cracking palm nuts on it. We
      measured the size and rate of pit formation, and recorded when adult and immature
      monkeys removed loose material from the anvil surface. We found that new pits
      were formed with approximately every 10 nuts cracked, (corresponding to an
      average of 38 strikes with a stone tool), and that adult males were the primary
      initiators of new pit positions on the anvil. Whole nuts were preferentially
      placed within pits for cracking, and partially-broken nuts outside the
      established pits. Visible anvil damage was rapid, occurring within a day of the
      anvil's introduction to the field laboratory. Destruction of the anvil through
      use has continued for three years since the experiment, resulting in both a
      pitted surface and a surrounding archaeological debris field that replicate
      features seen at natural FBV anvils. 

PMID- 25372880
TI  - Cellular responses associated with ROS production and cell fate decision in early
      stress response to iron limitation in the diatom Thalassiosira pseudonana.
AB  - Investigation of how diatoms cope with the rapid fluctuations in iron
      bioavailability in marine environments may facilitate a better understanding of
      the mechanisms underlying their ecological success, in particular their ability
      to proliferate rapidly during favorable conditions. In this study, using in vivo
      biochemical markers and whole-cell iTRAQ-based proteomics analysis, we explored
      the cellular responses associated with reactive oxygen species (ROS) production
      and cell fate decision during the early response to Fe limitation in the centric
      diatom Thalassiosira pseudonana. Fe limitation caused a significant decrease in
      Photosystem (PS) II photosynthetic efficiency, damage to the photosynthetic
      electron transport chain in PS I, and blockage of the respiratory chain in
      complexes III and IV, which could all result in excess ROS accumulation. The
      increase in ROS likely triggered programmed cell death (PCD) in some of the Fe
      limited cells through synthesis of a series of proteins involved in the delicate
      balance between pro-survival and pro-PCD factors. The results provide molecular
      level insights into the major strategies that may be employed by T. pseudonana in
      response to Fe-limitation: the reduction of cell population density through PCD
      to reduce competition for available Fe, the reallocation of intracellular
      nitrogen and Fe to ensure survival, and an increase in expression of antioxidant
      and anti-PCD proteins to cope with stress. 

PMID- 25372883
TI  - Controlled assembly and single electron charging of monolayer protected Au144
      clusters: an electrochemistry and scanning tunneling spectroscopy study.
AB  - Single gold particles may serve as room temperature single electron memory units
      because of their size dependent electronic level spacing. Here, we present a
      proof-of-concept study by electrochemically controlled scanning probe experiments
      performed on tailor-made Au particles of narrow dispersity. In particular, the
      charge transport characteristics through chemically synthesized hexane-1-thiol
      and 4-pyridylbenzene-1-thiol mixed monolayer protected Au(144) clusters (MPCs) by
      differential pulse voltammetry (DPV) and electrochemical scanning tunneling
      spectroscopy (EC-STS) are reported. The pyridyl groups exposed by the Au-MPCs
      enable their immobilization on Pt(111) substrates. By varying the humidity during
      their deposition, samples coated by stacks of compact monolayers of Au-MPCs or
      decorated with individual, laterally separated Au-MPCs are obtained. DPV
      experiments with stacked monolayers of Au(144)-MPCs and EC-STS experiments with
      laterally separated individual Au(144)-MPCs are performed both in aqueous and
      ionic liquid electrolytes. Lower capacitance values were observed for individual
      clusters compared to ensemble clusters. This trend remains the same irrespective
      of the composition of the electrolyte surrounding the Au(144)-MPC. However, the
      resolution of the energy level spacing of the single clusters is strongly
      affected by the proximity of neighboring particles.

PMID- 25372882
TI  - Altered resting-state amygdala functional connectivity after 36 hours of total
      sleep deprivation.
AB  - OBJECTIVES: Recent neuroimaging studies have identified a potentially critical
      role of the amygdala in disrupted emotion neurocircuitry in individuals after
      total sleep deprivation (TSD). However, connectivity between the amygdala and
      cerebral cortex due to TSD remains to be elucidated. In this study, we used
      resting-state functional MRI (fMRI) to investigate the functional connectivity
      changes of the basolateral amygdala (BLA) and centromedial amygdala (CMA) in the
      brain after 36 h of TSD. MATERIALS AND METHODS: Fourteen healthy adult men aged
      25.9 +/- 2.3 years (range, 18-28 years) were enrolled in a within-subject
      crossover study. Using the BLA and CMA as separate seed regions, we examined
      resting-state functional connectivity with fMRI during rested wakefulness (RW)
      and after 36 h of TSD. RESULTS: TSD resulted in a significant decrease in the
      functional connectivity between the BLA and several executive control regions
      (left dorsolateral prefrontal cortex [DLPFC], right dorsal anterior cingulate
      cortex [ACC], right inferior frontal gyrus [IFG]). Increased functional
      connectivity was found between the BLA and areas including the left posterior
      cingulate cortex/precuneus (PCC/PrCu) and right parahippocampal gyrus. With
      regard to CMA, increased functional connectivity was observed with the rostral
      anterior cingulate cortex (rACC) and right precentral gyrus. CONCLUSION: These
      findings demonstrate that disturbance in amygdala related circuits may contribute
      to TSD psychophysiology and suggest that functional connectivity studies of the
      amygdala during the resting state may be used to discern aberrant patterns of
      coupling within these circuits after TSD.

PMID- 25372886
TI  - An Overview: The Future of Plan Performance Measurement.
AB  - The papers featured in this issue of the Health Care Financing Review were
      presented at the "Conference on the Future of Plan Performance Measurement." This
      conference was held on May 2-3, 2000, in Towson, Maryland and was sponsored by
      the Health Care Financing Administration under a contract with the Barents Group
      of KPMG Consulting, Inc. in affiliation with Harvard Medical School, the MEDSTAT
      Group, and Westat. The conference was intended to inform stakeholders involved in
      Medicare health plans on future trends in the development and use of performance
      measures.

PMID- 25372884
TI  - Overweight and obesity in Portuguese children: prevalence and correlates.
AB  - There are widespread differences in overweight/obesity prevalence in children,
      and understanding the reasons for this is very important. The present study aims:
      (I) to conduct a meta-analysis on overweight/obesity prevalence in Portuguese
      children; (II) to identify differences in biological and behavioural
      characteristics between normal-weight and overweight/obese children; and (III) to
      investigate the importance of individual- and school-level correlates of
      variation in children's BMI using multilevel modelling. A search was done for all
      published papers including Portuguese children during the last decade; further,
      686 Portuguese children (9-11 years old) were sampled and their BMI, family
      income, maturity offset, nutritional habits, physical activity, sedentariness,
      sleep time, and school environment information were collected. Results showed a
      stabilization of overweight/obesity during the last decade, 30.6% (95%CI: 0.287
      0.34) for boys, 28.4% (95%CI: 0.23-0.35) for girls, and 30.3% (95%CI: 0.27-0.34)
      for boys and girls together. Differences between weight groups were only found in
      individual-level biological traits. The multilevel analysis did not identify
      significant contributions of school-level variables to children's BMI variation.
      In conclusion, no increase was found in the prevalence of overweight/obesity
      among Portuguese children since 2000. Normal-weight and overweight/obese children
      only differ in individual-level characteristics, and school context variables
      were not related to variation in BMI.

PMID- 25372887
TI  - Medicare Matters: Building on a Record of Accomplishments.
AB  - Medicare's successes over the past 35 years include doubling the number of
      persons age 65 or over with health insurance, increasing access to mainstream
      health care services, and substantially reducing the financial burdens faced by
      older Americans. Medicare reform remains high on the list of priorities of many
      policymakers because of rapid past and expected future growth in Medicare. If the
      original goals of the program-including providing mainstream care, pooling of
      risks, and offering help to those most in need-are to be protected, however, a go
      slow approach for greater reliance on the private sector is in order.

PMID- 25372889
TI  - Overview.

PMID- 25372888
TI  - Methyl/phenyl attraction by CH/pi interaction in 1,2-substitution patterns.
AB  - In 1,2-Me,Ph substitution patterns of organic compounds the methyl group attracts
      one of the phenyl sides to establish a CH/pi bond with one of the ortho carbon
      atoms (the C(o) side), leading to a characteristic tilting of the phenyl ring
      around its C(i)-C(p) axis. This phenyl rotation shortens the C(Me)-C(o) distances
      to bonding contacts between the methyl hydrogen atoms and the ortho carbon atom
      C(o) well below the van der Waals distance of 3.70 A. On the other hand, it
      elongates the C(Me)-C(o') distances outside of the reach of any CH/pi interaction
      (>3.70 A). Our study is based on a search in the Cambridge Structural Database
      for substructures Me-C?C-Ph, Me-C-C-Ph, and Me-C-N-Ph with 1,2-Me,Ph substitution
      patterns. In the 1,2-Me,Ph substitution motif the torsion angle C(Me)-C-C-C(i)
      determines the length of the C(Me)-C(i) and C(Me)-C(o) distances. For aromatic
      compounds these torsion angles are close to 0 degrees , but in five- and six
      membered ring compounds and in open-chain compounds the torsion angles vary
      considerably. Universally, for torsion angles up to 80 degrees  CH/pi bonds were
      found, whereas the long C(Me)-C(i) and C(Me)-C(o) distances for torsion angles
      >80 degrees  do not allow a CH/pi interaction. The results of the present CSD
      analysis are supported by calculations.

PMID- 25372891
TI  - Previous Medicaid Status of Children Newly Enrolled in Supplemental Security
      Income.
AB  - The Supplemental Security Income (SSI) program for children and adolescents has
      experienced a fourfold enrollment growth since 1989. Most SSI recipients also
      receive Medicaid, and SSI growth could therefore lead to major new Medicaid
      expenditures if new SSI recipients were not previous Medicaid enrollees. Using
      Medicaid claims for 1989-92, we determined whether SSI expansions included many
      children new to Medicaid as well as whether children with certain disabilities
      were more likely to have had Medicaid prior to SSI enrollment. Rates of new SSI
      enrollees without previous Medicaid coverage decreased from 53 percent in 1989 to
      39 percent by 1992.

PMID- 25372890
TI  - Influence of concomitant medications on the total clearance and the risk for
      supra-therapeutic plasma concentrations of Citalopram. A population-based cohort
      study.
AB  - INTRODUCTION: The main objective of this study was to investigate the influence
      of the use of multiple medications and other risk factors on citalopram plasma
      concentrations. METHODS: A retrospective cohort study with a naturalistic
      population of 957 patients for whom routine therapeutic drug monitoring (TDM) of
      citalopram had been requested between 2006 and 2013 was conducted. RESULTS:
      Concomitant drugs inhibiting at least 2 different CYP subtypes involved in the
      metabolism of citalopram decreased statistically significantly the total
      clearance (Clt). Compared to younger patients over 64-year-old patients had on
      average a 4.5 times higher risk rate of supra-therapeutic plasma concentrations.
      However, binary logistic regression showed that age, sex and co-medication
      accounted only for 26% of the inter-individual variability of citalopram plasma
      concentrations. DISCUSSION: Due to pharmacokinetic interactions, citalopram
      plasma concentrations are often higher than expected with a given dose.
      Especially in geriatric and often multimorbid patients who are usually prescribed
      high numbers of concomitant drugs and are at higher risk for adverse drug
      reactions (ADR), restriction of the maximal dose of citalopram is not sufficient
      to prevent supra-therapeutic plasma concentrations.

PMID- 25372892
TI  - Clinical uncertainty at the intersection of advancing technology, evidence-based
      medicine, and health care policy.

PMID- 25372893
TI  - Synthesis of liquid core-shell particles and solid patchy multicomponent
      particles by shearing liquids into complex particles (SLICE).
AB  - We report a simple method that uses (i) emulsion shearing with oxidation to make
      core-shell particles, and (ii) emulsion shearing with surface-tension driven
      phase segregation to synthesize particles with complex surface compositions and
      morphologies. Subjecting eutectic gallium-indium, a liquid metal, to shear in an
      acidic carrier fluid we synthesized smooth liquid core-shell particles 6.4 nm to
      over 10 MUm in diameter. Aggregates of these liquid particles can be reconfigured
      into larger structures using a focused ion beam. Using Field's metal melts we
      synthesized homogeneous nanoparticles and solid microparticles with different
      surface roughness and/or composition through shearing and phase separation. This
      extension of droplet emulsion technique, SLICE, applies fluidic shear to create
      micro- and nanoparticles in a tunable, green, and low-cost approach. 

PMID- 25372895
TI  - Inpatient Psychiatric Care of Medicare Beneficiaries With State Buy-In Coverage.
AB  - Administrative data were used to compare lengths of stay, Medicare payment, total
      and average daily costs, discharge destinations, rehospitalizations, and
      emergency room (ER) use of dually eligible and non-dually eligible Medicare
      inpatients admitted for a psychiatric diagnosis. Regressions controlled for State
      buy-in coverage as a proxy for dual eligibility, hospital type, and beneficiary
      sociodemographic and clinical characteristics. Measures of severity within
      diagnostic category were limited to comorbidities. Among disabled beneficiaries,
      dually eligible beneficiaries had lower costs and shorter stays. Among elderly
      and disabled persons, dually eligible beneficiaries had higher rates of
      rehospitalization, post-discharge ER use without admission, and discharge to
      destinations other than self-care.

PMID- 25372894
TI  - Great apes and biodiversity offset projects in Africa: the case for national
      offset strategies.
AB  - The development and private sectors are increasingly considering "biodiversity
      offsets" as a strategy to compensate for their negative impacts on biodiversity,
      including impacts on great apes and their habitats in Africa. In the absence of
      national offset policies in sub-Saharan Africa, offset design and implementation
      are guided by company internal standards, lending bank standards or international
      best practice principles. We examine four projects in Africa that are seeking to
      compensate for their negative impacts on great ape populations. Our assessment of
      these projects reveals that not all apply or implement best practices, and that
      there is little standardization in the methods used to measure losses and gains
      in species numbers. Even if they were to follow currently accepted best-practice
      principles, we find that these actions may still fail to contribute to
      conservation objectives over the long term. We advocate for an alternative
      approach in which biodiversity offset and compensation projects are designed and
      implemented as part of a National Offset Strategy that (1) takes into account the
      cumulative impacts of development in individual countries, (2) identifies
      priority offset sites, (3) promotes aggregated offsets, and (4) integrates
      biodiversity offset and compensation projects with national biodiversity
      conservation objectives. We also propose supplementary principles necessary for
      biodiversity offsets to contribute to great ape conservation in Africa. Caution
      should still be exercised, however, with regard to offsets until further field
      based evidence of their effectiveness is available. 

PMID- 25372896
TI  - Stereotactic radiosurgery for facial nerve schwannomas: A preliminary assessment
      and review of the literature.
AB  - OBJECTIVE: Facial nerve schwannomas (FNS) are rare tumors, and their appropriate
      management remains the subject of considerable debate. This report details the
      results of a series of patients with FNS treated with stereotactic radiosurgery
      (SRS) at the University of Virginia. METHODS: We performed a retrospective review
      of the clinical and imaging outcomes of 5 patients who underwent Gamma Knife RS
      (GKRS) for small-to-medium-sized (<5 mL) FNS at our institution. The study
      population consisted of 3 males and 2 females with a median age of 35 years. All
      patients presented with varying degrees of facial palsy and/or hearing
      dysfunction. Tumor volumes at GKRS ranged from 0.1 to 5 (median=0.8) mL. The
      median maximum radiosurgical dose and tumor margin dose were 24 Gy and 12 Gy,
      respectively. RESULTS: After a median follow-up period of 12 (range, 6-36)
      months, three tumors were radiographically smaller and two remained stable.
      Facial function improved in three patients, remained stable in one patient, and
      slightly declined from House-Brackmann grade I to II in one patient. Hearing
      function was preserved in three patients and deteriorated in two patients, one
      from Gardner-Robertson grade I to II and the other from serviceable hearing grade
      II to III. CONCLUSION: SRS appears to offer a reasonable rate of facial nerve
      preservation and tumor control for patients with small-to-medium-sized FNS.
      Considering the published outcomes achieved with resection, RS may be the
      preferred first-line treatment for these tumors.

PMID- 25372897
TI  - Cost and Financing of Care for Persons With HIV Disease: An Overview.
AB  - This article explores the impact of new combination drug therapies on the cost
      and financing of human immunodeficiency virus (HIV) disease. Evidence indicates
      that the proportion of costs attributable to drugs has increased significantly
      since the diffusion of new combination drug therapies, and that the proportion of
      costs attributable to hospital inpatient care has decreased. The absence of
      timely data is the major difficulty in analyzing the impact of recent changes.
      Only two studies have examined costs since the diffusion of new combination drug
      therapies, and there are no recent studies of the insurance status of persons
      with HIV disease.

PMID- 25372898
TI  - Insight into the time-resolved extraction of aroma compounds during espresso
      coffee preparation: online monitoring by PTR-ToF-MS.
AB  - Using proton-transfer-reaction time-of-flight mass-spectrometry (PTR-ToF-MS), we
      investigated the extraction dynamic of 95 ion traces in real time (time
      resolution = 1 s) during espresso coffee preparation. Fifty-two of these ions
      were tentatively identified. This was achieved by online sampling of the volatile
      organic compounds (VOCs) in close vicinity to the coffee flow, at the exit of the
      extraction hose of the espresso machine (single serve capsules). Ten replicates
      of six different single serve coffee types were extracted to a final weight
      between 20-120 g, according to the recommended cup size of the respective coffee
      capsule (Ristretto, Espresso, and Lungo), and analyzed. The results revealed
      considerable differences in the extraction kinetics between compounds, which led
      to a fast evolution of the volatile profiles in the extract flow and consequently
      to an evolution of the final aroma balance in the cup. Besides exploring the time
      resolved extraction dynamics of VOCs, the dynamic data also allowed the coffees
      types (capsules) to be distinguished from one another. Both hierarchical cluster
      analysis (HCA) and principal component analysis (PCA) showed full separation
      between the coffees types. The methodology developed provides a fast and simple
      means of studying the extraction dynamics of VOCs and differentiating between
      different coffee types. 

PMID- 25372899
TI  - UV absorption probing of the conformer-dependent reactivity of a Criegee
      intermediate CH3CHOO.
AB  - We measure the UV absorption spectrum of a Criegee intermediate acetaldehyde
      oxide, CH3CHOO, using time-resolved broadband cavity-enhanced spectrometry. We
      separate the spectra of the two possible structural isomers, syn- and anti
      CH3CHOO, based on their different reactivity towards H2O and SO2. Despite
      significant overlap, the spectra of the two conformers are sufficiently separated
      to allow direct conformer-specific probing of the reactions of CH3CHOO with other
      important tropospheric species. 

PMID- 25372900
TI  - BJCVS in PubMed Central.

PMID- 25372901
TI  - Acute kidney injury based on KDIGO (Kidney Disease Improving Global Outcomes)
      criteria in patients with elevated baseline serum creatinine undergoing cardiac
      surgery.
AB  - INTRODUCTION: Preoperatively elevated serum creatinine (SCr) is considered an
      independent risk factor for morbidity and mortality after cardiac surgery. The
      aim of this study was to apply the Kidney Disease Improving Global Outcomes
      classification for acute kidney injury in a population of patients with
      preoperatively elevated serum creatinine who underwent cardiac surgery (coronary
      artery bypass grafting or cardiac valve surgery) and to evaluate the acute
      worsening of renal function as a predictor of 30-day mortality. METHODS: This was
      a single-center retrospective study that included patients from the Postoperative
      Cardiac Surgery Intensive Care Unit of the Hospital de Base, Sao Jose do Rio
      Preto Medical School. Demographics, type of surgery, laboratory data and pre,
      peri and postoperative data were obtained from a prospectively collected
      database. From January 2003 to June 2013, 2,878 patients underwent cardiac
      surgery, either coronary artery bypass grafting or cardiac valve surgery, at the
      Hospital de Base of Sao Jose do Rio Preto Medical School. Out of those, 918
      showed elevated preoperative serum creatinine, with SCr > 1.30 mg/dL for men and
      > 1.00 mg/dL for women. Five hundred and forty nine patients (60%) undergoing
      coronary artery bypass grafting and 369 patients (40%) undergoing cardiac valve
      surgery. A Multivariate Cox Proportional Hazard Model (stepwise) was used to
      assess the relationship between AKI and mortality at 30 days. RESULTS: Out of the
      918 patients studied, 391 (43%) had postoperative AKI: 318 (35%) had Kidney
      Disease Improving Global Outcomes stage 1, 27 (2.9%) had Kidney Disease Improving
      Global Outcomes stage 2, and 46 (5.0%) had Kidney Disease Improving Global
      Outcomes stage 3. Patients in every stage of acute kidney injury showed
      progressive increase in EuroSCORE values, 30-day mortality rates, cardiopulmonary
      bypass duration, and intensive care length of stay. Among patients classified as
      Kidney Disease Improving Global Outcomes stage 3, 76% required dialysis with a 30
      day mortality of 66%. The Cox proportional hazards model showed that the hazard
      ratio for 30-day mortality was 4.8 for Kidney Disease Improving Global Outcomes
      stage 1 patients, 13.5 for Kidney Disease Improving Global Outcomes stage 2
      patients, and 20.8 for Kidney Disease Improving Global Outcomes stage 3 patients
      (P<0.001 for all). Subgroup analyses (coronary artery bypass grafting and cardiac
      valve surgery) had similar results. CONCLUSION: In this population, acute kidney
      injury based on the Kidney Disease Improving Global Outcomes criteria was a
      powerful predictor of 30-day mortality in patients with elevated preoperative
      serum creatinine who underwent cardiac surgery (coronary artery bypass grafting
      or cardiac valve surgery).

PMID- 25372902
TI  - Chronic stress and coping among cardiac surgeons: a single center study.
AB  - INTRODUCTION: Cardiac surgeons stress may impair their quality of life and
      professional practice. OBJECTIVE: To assess perceived chronic stress and coping
      strategies among cardiac surgeons. METHODS: Twenty-two cardiac surgeons answered
      two self-assessment questionnaires, the Trier Inventory for Chronic Stress and
      the German SGV for coping strategies. RESULTS: Participants mean age was 40+/
      14.1 years and 13 were male; eight were senior physicians and 14 were residents.
      Mean values for the Trier Inventory for Chronic Stress were within the normal
      range. Unexperienced physicians had significantly higher levels of
      dissatisfaction at work, lack of social recognition, and isolation (P<0.05).
      Coping strategies such as play down, distraction from situation, and
      substitutional satisfaction were also significantly more frequent among
      unexperienced surgeons. "Negative" stress-coping strategies occur more often in
      experienced than in younger colleagues (P=0.029). Female surgeons felt more
      exposed to overwork (P=0.04) and social stress (P=0.03). CONCLUSION: Cardiac
      surgeons show a tendency to high perception of chronic stress phenomena and
      vulnerability for negative coping strategies.

PMID- 25372903
TI  - Late outcome analysis of the Braile Biomedica(r) pericardial valve in the aortic
      position.
AB  - OBJECTIVE: Aortic valve replacement with Braile bovine pericardial prosthesis has
      been routinely done at the Heart Institute of the Universidade de Sao Paulo
      Medical School since 2006. The objective of this study is to analyze the results
      of Braile Biomedica(r) aortic bioprosthesis in patients with aortic valve
      disease. METHODS: We retrospectively evaluated 196 patients with aortic valve
      disease submitted to aortic valve replacement with Braile Biomedica(r) bovine
      pericardial prosthesis, between 2006 and 2010. Mean age was 59.41+/-16.34 years
      and 67.3% were male. Before surgery, 73.4% of patients were in NYHA functional
      class III or IV. RESULTS: Hospital mortality was 8.16% (16 patients). Linearized
      rates of mortality, endocarditis, reintervention, and structural dysfunction were
      1.065%, 0.91%, 0.68% and 0.075% patients/year, respectively. Actuarial survival
      was 90.59+/-2.56% in 88 months. Freedom from reintervention, endocarditis and
      structural dysfunction was respectively 91.38+/-2.79%, 89.84+/-2.92% and 98.57+/
      0.72% in 88 months. CONCLUSION: The Braile Biomedica(r) pericardial aortic valve
      prosthesis demonstrated actuarial survival and durability similar to that
      described in the literature, but further follow up is required to assess the
      incidence of prosthetic valve endocarditis and structural dysfunction in the
      future.

PMID- 25372904
TI  - Pediatric and congenital heart transplant: twenty-year experience in a tertiary
      Brazilian hospital.
AB  - INTRODUCTION: Cardiac transplantation remains the gold standard for end-stage
      cardiomyopathies and congenital heart defects in pediatric patients. OBJECTIVE:
      This study aims to report on 20 years of experience since the first case and
      evaluate our results. METHODS: We conducted a retrospective analysis of the
      database and outpatient follow-up. Between October 1992 and April 2012, 109
      patients underwent 114 transplants. 51.8% of them being female. The age of
      patients ranged from 12 days to 21 years with a mean of 8.8+/-5.7 years and a
      median of 5.2 years. The underlying diagnosis was dilated cardiomyopathy in
      61.5%, congenital heart disease in 26.6% and restrictive cardiomyopathy in 11.9%.
      All patients above 17 years old had congenital heart disease. RESULTS: Survival
      rate at 30 days, 1, 5, 10, 15, and 20 years were 90.4%, 81.3%, 70.9%, 60.5%,
      44.4% and 26.7%, respectively. Mean cold ischemic time was 187.9 minutes and it
      did not correlate with mortality (P>0.05). Infectious complications and rejection
      episodes were the most common complications (P<0.0001), occurring, respectively,
      in 66% and 57.4% of the survivors after 10 years. There was no incidence of graft
      vascular disease and lymphoproliferative disease at year one, but they affected,
      respectively, 7.4% and 11% of patients within 10 years. CONCLUSION: Twenty-year
      pediatric heart transplant results at our institution were quite satisfactory and
      complication rates were acceptable.

PMID- 25372905
TI  - Clinical evaluation of the Spiral Pump(r) after improvements to the original
      project in patients submitted to cardiac surgeries with cardiopulmonary bypass.
AB  - OBJECTIVE: The objective of this paper is to present the results from Spiral Pump
      clinical trial after design modifications performed at its previous project. This
      pump applies axial end centrifugal hydraulic effects for blood pumping during
      cardiopulmonary bypass for patients under cardiac surgery. METHODS: This study
      was performed in 52 patients (51% males), between 20 to 80 (67+/-14.4) years old
      weighing 53 to 102 (71.7+/-12.6) kg, mostly under myocardial revascularization
      surgery (34.6%) and valvular surgery (32.8%). Besides the routine evaluation of
      the data observed in these cases, we monitored pump rotational speed, blood flow,
      cardiopulmonary bypass duration, urine free hemoglobin for blood cell trauma
      analysis (+ to 4+), lactate desidrogenase (UI/L), fibrinogen level (mg/dL) and
      platelet count (no/mm3). RESULTS: Besides maintaining appropriate blood pressure
      and metabolic parameters it was also observed that the Free Hemoglobin levels
      remained normal, with a slight increase after 90 minutes of cardiopulmonary
      bypass. The Lactate Dehydrogenase showed an increase, with medians varying
      between 550-770 IU/L, whereas the decrease in Fibrinogen showed medians of 130
      100 mg/dl. The number of platelets showed a slight decrease with the medians
      ranging from 240,000 to 200,000/mm3. No difficulty was observed during perfusion
      terminations, nor were there any immediate deaths, and all patients except one,
      were discharged in good condition. CONCLUSION: The Spiral Pump, as blood
      propeller during cardiopulmonary bypass, demonstrated to be reliable and safe,
      comprising in a good option as original and national product for this kind of
      application.

PMID- 25372906
TI  - Idiopathic dilated cardiomyopathy: computerized anatomic study of relashionship
      between septal and free left ventricle wall.
AB  - INTRODUCTION: A feature of dilated cardiomyopathy is the deformation of
      ventricular cavity, which contributes to systolic dysfunction. Few studies have
      evaluated this deformation bearing in mind ventricular regions and segments of
      the ventricle, which could reveal important details of the remodeling process,
      supporting a better understanding of its role in functional impairment and the
      development of new therapeutic strategies. OBJECTIVE: To evaluate if, in basal,
      equatorial and apical regions, increased internal transverse perimeter of left
      ventricle in idiopathic dilated cardiomyopathy occurs proportionally between the
      septal and non-septal segment. METHODS: We performed an anatomical study with 28
      adult hearts from human cadavers. One group consisted of 18 hearts with
      idiopathic dilated cardiomyopathy and another group with 10 normal hearts. After
      lamination and left ventricle digital image capture, in three different regions
      (base, equator and apex), the transversal internal perimeter of left ventricle
      was divided into two segments: septal and not septal. These segments were
      measured by proper software. It was established an index of proportionality
      between these segments, called septal and non-septal segment index. Then we
      determined whether this index was the same in both groups. RESULTS: Among
      patients with normal hearts and idiopathic dilated cardiomyopathy, the index of
      proportionality between the two segments (septal and non-septal) showed no
      significant difference in the three regions analyzed. The comparison results of
      the indices NSS/SS among normal and enlarged hearts were respectively: in base
      1.99 versus 1.86 (P=0.46), in equator 2.22 versus 2.18 (P=0.79) and in apex 2.96
      versus 3.56 (P=0.11). CONCLUSION: In the idiopathic dilated cardiomyopathy, the
      transversal dilatation of left ventricular internal perimeter occurs
      proportionally between the segments corresponding to the septum and free wall at
      the basal, equatorial and apical regions of this chamber.

PMID- 25372907
TI  - Addition of long-distance heart procurement promotes changes in heart transplant
      waiting list status.
AB  - OBJECTIVE: Evaluate the addition of long-distance heart procurement on a heart
      transplant program and the status of heart transplant recipients waiting list.
      METHODS: Between September 2006 and October 2012, 72 patients were listed as
      heart transplant recipients. Heart transplant was performed in 41 (57%), death on
      the waiting list occurred in 26 (36%) and heart recovery occurred in 5 (7%).
      Initially, all transplants were performed with local donors. Long-distance,
      interstate heart procurement initiated in February 2011. Thirty (73%) transplants
      were performed with local donors and 11 (27%) with long-distance donors (mean
      distance=792 km+/-397). RESULTS: Patients submitted to interstate heart
      procurement had greater ischemic times (212 min +/- 32 versus 90 min+/-18;
      P<0.0001). Primary graft dysfunction (distance 9.1% versus local 26.7%; P=0.23)
      and 1 month and 12 months actuarial survival (distance 90.1% and 90.1% versus
      local 90% and 86.2%; P=0.65 log rank) were similar among groups. There were
      marked incremental transplant center volume (64.4% versus 40.7%, P=0.05) with a
      tendency on less waiting list times (median 1.5 month versus 2.4 months, P=0.18).
      There was a tendency on reduced waiting list mortality (28.9% versus 48.2%,
      P=0.09). CONCLUSION: Incorporation of long-distance heart procurement, despite
      being associated with longer ischemic times, does not increase morbidity and
      mortality rates after heart transplant. It enhances viable donor pool, and it may
      reduce waiting list recipient mortality as well as waiting time.

PMID- 25372908
TI  - Psychological assessment of patients undergoing cardiac transplant in a teaching
      hospital (2004 to 2012).
AB  - OBJECTIVE: To analyze the psychological evaluations of patients with heart
      failure waiting for heart transplantation. METHODS: The data were obtained from
      patient records containing pre-surgery psychological evaluations performed by
      psychologists from the multidisciplinary cardiology team. The evaluation protocol
      included the Quality of Life Questionnaire (SF-36), Beck Depression Inventory,
      and an interview script. RESULTS: The results of psychological evaluations
      performed between 2004 and 2012 for 60 candidates for heart transplantation were
      analyzed: 43 men and 17 women aged between 16 and 66 years (Mean=45.18;
      SD=11.91), predominantly from the Sao Jose do Rio Preto area (Sao Paulo state,
      Brazil) (83%), with incomplete elementary education (68%), and who were in stable
      relationships (73%). Although women presented higher mean scores for depression
      (21.41) than men (14.61), there was no significant difference between genders.
      Women's quality of life was impaired in all domains compared to men (below 50%)
      and was significantly poorer in the physical functioning (P=0.01), vitality
      (P=0.00), emotional role functioning (P=0.04), and mental health (P=0.02)
      domains. CONCLUSION: Patients with psychosocial vulnerability (e.g., depression)
      identified before transplantation should receive psychological treatment.

PMID- 25372909
TI  - Evaluation of peripheral muscle strength of patients undergoing elective cardiac
      surgery: a longitudinal study.
AB  - INTRODUCTION: Peripheral muscle strength has been little explored in the
      literature in the context of cardiac rehabilitation. OBJECTIVE: To evaluate the
      peripheral muscle strength of patients undergoing elective cardiac surgery.
      METHODS: This was a longitudinal observational study. The peripheral muscle
      strength was measured using isometric dynamometry lower limb (knee extensors and
      flexors) at three different times: preoperatively (M1), the day of discharge (M2)
      and hospital discharge (M3). Participants received physiotherapy pre and
      postoperatively during the days of hospitalization during the morning and
      afternoon. RESULTS: Twenty-two patients were evaluated. The values of peripheral
      muscle strength of knee extensors preoperative found were about 50% lower than
      those predicted for the healthy population. When comparing muscle strength prior
      (M1), with the remaining evaluation, found himself in a fall of 29% for the
      movement of knee extension and 25% for knee flexion in M2 and a decrease of 10%
      movement for knee extension and 13% for knee flexion in M3 when comparing with
      M1. CONCLUSION: The values of peripheral muscle strength prior of the study
      patients were lower than predicted for the healthy population of the same age.
      After the surgical event this reduction is even more remarkable, being
      reestablished until the time of discharge, to values close to baseline.

PMID- 25372910
TI  - Does homeostasis model assessment of insulin resistance have a predictive value
      for post-coronary artery bypass grafting surgery outcomes?
AB  - OBJECTIVE: This study aims to investigate whether pre-operative Homeostasis Model
      Assessment Insulin Resistance (HOMA-IR) value is a predictor in non-diabetic
      coronary artery bypass grafting patients in combination with hemoglobin A1c,
      fasting blood glucose and insulin levels. METHODS: Eighty one patients who were
      admitted to Cardiovascular Surgery Clinic at our hospital between August 2012 and
      January 2013 with a coronary artery bypass grafting indication were included.
      Patients were non-diabetic with <6.3% hemoglobin A1c and were divided into two
      groups including treatment and control groups according to normal insulin
      resistance (HOMA-IR<2.5, Group A; n=41) and high insulin resistance (HOMA-IR>2.5,
      Group B; n=40), respectively. Pre-operative fasting blood glucose and insulin
      were measured and serum chemistry tests were performed. The Homeostasis Model
      Assessment Insulin Resistance values were calculated. Statistical analysis was
      performed. RESULTS: There was a statistically significant difference in fasting
      blood glucose and HOMA-IR values between the groups. Cross-clamping time, and
      cardiopulmonary bypass time were longer in Group B, compared to Group A (P=0.043
      and P=0.031, respectively). Logistic regression analysis revealed that hemoglobin
      A1c was not a reliable determinant factor alone for pre-operative glucometabolic
      evaluation of non-diabetic patients. The risk factors of fasting blood glucose
      and cardiopulmonary bypass time were more associated with high Homeostasis Model
      Assessment Insulin Resistance levels. CONCLUSION: Our study results suggest that
      preoperative screening of non-diabetic patients with Homeostasis Model Assessment
      Insulin Resistance may improve both follow-up visit schedule and short-term
      outcomes, and may be useful in risk stratification of the high-risk population
      for impending health problems.

PMID- 25372911
TI  - Comparison of superior septal approach with left atriotomy in mitral valve
      surgery.
AB  - OBJECTIVE: In this study, we aimed to compare clinical outcomes of superior
      transseptal approach with the conventional left atriotomy in patients undergoing
      mitral valve surgery. METHODS: Between January 2010 and November 2012, a total of
      91 consecutive adult patients (39 males, 52 females; mean age: 54.0+/-15.4 years;
      range, 16 to 82 years) who underwent mitral valve surgery in the Division of
      Cardiovascular Surgery at Kosuyolu Training Hospital were included. The patients
      were randomized to either superior transseptal approach (n=47) or conventional
      left atriotomy (n=44). Demographic characteristics of the patients,
      comorbidities, additional interventions, intraoperational data, pre- and
      postoperative electrophysiological study findings, and postoperative
      complications were recorded. RESULTS: Of all patients, 86.7% (n=79) were in New
      York Heart Association Class III, while 12 were in New York Heart Association
      Class IV. All patients underwent annuloplasty (42.9%) or valve replacement
      surgery (57.1%). There was no significant difference in pre- and postoperative
      electrocardiogram findings between the groups. Change from baseline in the
      cardiac rhythm was statistically significant in superior transseptal approach
      group alone (P<0.001). There was no statistically significant difference in
      mortality rate between the groups. Permanent pacemaker implantation was performed
      in 10.6% of the patients in superior transseptal approach group and 4.5% in the
      conventional left atriotomy group. No statistically significant difference in
      bleeding, total length of hospital and intensive care unit stay, the presence of
      low cardiac output syndrome was observed between the groups. CONCLUSION: Our
      study results suggest that superior transseptal approach does not lead to serious
      or fatal adverse effects on sinus node function or atrial vulnerability, compared
      to conventional approach.

PMID- 25372912
TI  - Benefit from using recycling red blood cells in cardiovascular surgery.
AB  - OBJECTIVE: To show if blood salvage is indicated in all patients submitted to
      cardiovascular surgery with cardiopulmonary bypass. METHODS: We studied 77
      consecutive patients submitted to cardiac surgery with use of blood salvage and
      cardiopulmonary bypass from November 2010 to June 2012. The sample was divided in
      three groups, depending on the time of cardiopulmonary bypass. In group A, the
      time of cardiopulmonary bypass was smaller than 45, in group B from 45 to 90 and
      in group C greater than 90 minutes. We analyzed the volume of red cells recovered
      and infused, the pre, intra and post-operative hemoglobin, the number of packed
      red cells units which were transfused and hematocrit and hemoglobin blood
      infused. RESULTS: The average group age was 60.44+/-12.09 years old, of whom
      71.43% were males. The group A was formed by 5.19% of the patients, B by 81.82%
      and C by 12.99%. The volume of erythrocytes recovered and infused was
      respectively 1,360.50+/-511.37 ml and 339.75+/-87.71 ml in group A, 1,436.63+/
      516.06 ml and 518.83+/-183.0 ml in B and 2,137.00+/-925.04 ml and 526.20+/-227.15
      ml in C. About packed red cells transfusions, in group A 1,00+/-2,00 packed red
      cells were transfused, in B 1.27+/-1.85 packed red cells and in C 2.56+/-2.01
      packed red cells. The infused blood had a hematocrit of 50.97+/-12.06% and
      hemoglobin of 19.57+/-8.35 g/dl. CONCLUSION: That blood salvage can be used in
      patients submitted to cardiovascular surgery with cardiopulmonary bypass.
      However, it is only cost-effective in surgeries in which the time of
      cardiopulmonary bypass is greater than 45 minutes.

PMID- 25372913
TI  - Results of heart transplantation in the urgent recipient--who should be
      transplanted?
AB  - OBJECTIVE: To evaluate immediate and long-term results of cardiac transplantation
      at two different levels of urgency. METHODS: From November 2003 to December 2012,
      228 patients underwent cardiac transplantation. Children and patients in
      cardiogenic shock were excluded from the study. From the final group (n=212), 58
      patients (27%) were hospitalized under inotropic support (Group A), while 154
      (73%) were awaiting transplantation at home (Group B). Patients in Group A were
      younger (52.0+/-11.3 vs. 55.2+/-10.4 years, P=0.050) and had shorter waiting
      times (29.4+/-43.8 vs. 48.8+/-45.2 days; P=0.006). No difference was found for
      sex or other comorbidities. Haemoglobin was lower and creatinine higher in Group
      A. The characteristics of the donors were similar. Follow-up was 4.5+/-2.7 years.
      RESULTS: No differences were found in time of ischemia (89.1+/-37.0 vs. 91.5+/
      34.5 min, P=0.660) or inotropic support (13.8% vs. 11.0%, P=0.579), neither in
      the incidence of cellular or humoral rejection and of cardiac allograft
      vasculopathy. De novo diabetes de novo in the first year was slightly higher in
      Group A (15.5% vs. 11.7%, P=0.456), and these patients were at increased risk of
      serious infection (22.4% vs. 12.3%, P=0.068). Hospital mortality was similar
      (3.4% vs. 4.5%, P=0.724), as well as long-term survival (7.8+/-0.5 vs. 7.4+/-0.3
      years). CONCLUSIONS: The results obtained in patients hospitalized under
      inotropic support were similar to those of patients awaiting transplantation at
      home. Allocation of donors to the first group does not seem to compromise the
      benefit of transplantation. These results may not be extensible to more critical
      patients.

PMID- 25372914
TI  - Fetal cardiac interventions: an update of therapeutic options.
AB  - OBJECTIVE: This article aims to present updated therapeutic options for fetal
      congenital heart diseases. METHODS: Data source for the present study was based
      on comprehensive literature retrieval on fetal cardiac interventions in terms of
      indications, technical approaches and clinical outcomes. RESULTS: About 5% of
      fetal congenital heart diseases are critical and timely intrauterine intervention
      may alleviate heart function. Candidates for fetal cardiac interventions are
      limited. These candidates may include critical aortic valve stenosis with
      evolving hypoplastic left heart syndrome, pulmonary atresia with an intact
      ventricular septum and evolving hypoplastic right heart syndrome, and hypoplastic
      left heart syndrome with an intact or highly restrictive atrial septum as well as
      fetal heart block. The advocated option are prenatal aortic valvuloplasty,
      pulmonary valvuloplasty, creation of atrial communication and fetal cardiac
      pacing. CONCLUSION: Fetal cardiac interventions are feasible at midgestation with
      gradually improved technical success and fetal/postnatal survival due mainly to a
      well-trained multidisciplinary team, sophisticated equipment and better postnatal
      care.

PMID- 25372915
TI  - Indication of endovascular treatment of type B aortic dissection--literature
      review.
AB  - Aortic dissection is a cardiovascular event of high mortality if not early
      diagnosed and properly treated. In Stanford type A aortic dissection, there is
      the involvement of the ascending aorta, whereas in type B the ascending aorta is
      not affected. The treatment of type A aortic dissection is mainly surgical. The
      hospital mortality of type B aortic dissection surgical treatment is
      approximately 20%, while medical therapy is 10%. However, half the patients who
      are discharged from hospital after medical treatment, progress to aortic
      complications in the following years, and the mortality in three to five years
      may reach 25-50%. In addition, the surgical treatment of aortic complications
      after medical treatment, has also a significant mortality. This way, the
      endovascular treatment comes up as an interesting alternative of a less invasive
      treatment for this disease. They presented a mortality rate lower than 10% with
      more than 80% success rate of occlusion and thrombosis of the false lumen. The
      INSTEAD TRIAL, which randomized patients with uncomplicated type B aortic
      dissection for optimal medical therapy and endovascular treatment in addition to
      optimal medical therapy, showed that after three years of follow up, patients who
      underwent endovascular treatment had lower mortality and aorta-related
      complications. Therefore, there is a current tendency to recommend the
      endovascular treatment as a standard for the treatment of type B aortic
      dissection. 

PMID- 25372916
TI  - Cardiomyopathy induced by artificial cardiac pacing: myth or reality sustained by
      evidence?
AB  - Implantable cardiac pacing systems are a safe and effective treatment for
      symptomatic irreversible bradycardia. Under the proper indications, cardiac
      pacing might bring significant clinical benefit. Evidences from literature state
      that the action of the artificial pacing system, mainly when the ventricular lead
      is located at the apex of the right ventricle, produces negative effects to
      cardiac structure (remodeling, dilatation) and function (dissinchrony). Patients
      with previously compromised left ventricular function would benefit the least
      with conventional right ventricle apical pacing, and are exposed to the risk of
      developing higher incidence of morbidity and mortality for heart failure.
      However, after almost 6 decades of cardiac pacing, just a reduced portion of
      patients in general would develop these alterations. In this context, there are
      not completely clear some issues related to cardiac pacing and the development of
      this cardiomyopathy. Causality relationships among QRS widening with a left
      bundle branch block morphology, contractility alterations within the left
      ventricle, and certain substrates or clinical (previous systolic dysfunction,
      structural heart disease, time from implant) or electrical conditions (QRS
      duration, percentage of ventricular stimulation) are still subjects of debate.
      This review analyses contemporary data regarding this new entity, and discusses
      alternatives of how to use cardiac pacing in this context, emphasizing cardiac
      resynchronization therapy.

PMID- 25372917
TI  - Postperfusion lung syndrome: physiopathology and therapeutic options.
AB  - Postperfusion lung syndrome is rare but can be lethal. The underlying mechanism
      remains uncertain but triggering inflammatory cascades have become an accepted
      etiology. A better understanding of the pathophysiology and the roles of
      inflammatory mediators in the development of the syndrome is imperative in the
      determination of therapeutic options and promotion of patients' prognosis and
      survival. Postperfusion lung syndrome is similar to adult respiratory distress
      syndrome in clinical features, diagnostic approaches and management strategies.
      However, the etiologies and predisposing risk factors may differ between each
      other. The prognosis of the postperfusion lung syndrome can be poorer in
      comparison to acute respiratory distress syndrome due to the secondary multiple
      organ failure and triple acid-base imbalance. Current management strategies are
      focusing on attenuating inflammatory responses and preventing from pulmonary
      ischemia-reperfusion injury. Choices of cardiopulmonary bypass circuit and
      apparatus, innovative cardiopulmonary bypass techniques, modified surgical
      maneuvers and several pharmaceutical agents can be potential preventive
      strategies for acute lung injury during cardiopulmonary bypass. 

PMID- 25372918
TI  - Sonocubic fine: new three-dimensional ultrasound software to the screening of
      congenital heart diseases.
AB  - Congenital heart disease is the most common fetal congenital malformations;
      however, the prenatal rate detection still is low. The two-dimensional
      echocardiography is the "gold standard" exam to screening and diagnosis of
      congenital heart disease during the prenatal; however, this exam is operator
      depending and it is realized only in high risk pregnancies. Spatio-temporal image
      correlation is a three-dimensional ultrasound software that analyses the fetal
      heart and your connections in the multiplanar and rendering modes; however,
      spatio-temporal image correlation too is operator-depending and time-consuming.
      We presenting a new three-dimensional software named Sonocubic fine to the
      screening of congenital heart disease. This software applies intelligent
      navigation technology to spatio-temporal image correlation volume datasets to
      automatically generate nine fetal echocardiography standard views. Thus, this new
      software tends to be less operator-depending and time-consuming. 

PMID- 25372919
TI  - Modes of induced cardiac arrest: hyperkalemia and hypocalcemia--literature
      review.
AB  - The entry of sodium and calcium play a key effect on myocyte subjected to cardiac
      arrest by hyperkalemia. They cause cell swelling, acidosis, consumption of
      adenosine triphosphate and trigger programmed cell death. Cardiac arrest caused
      by hypocalcemia maintains intracellular adenosine triphosphate levels, improves
      diastolic performance and reduces oxygen consumption, which can be translated
      into better protection to myocyte injury induced by cardiac arrest. 

PMID- 25372920
TI  - Direct intramyocardial transthoracic transplantation of bone marrow mononuclear
      cells for non-ischemic dilated cardiomyopathy: INTRACELL, a prospective
      randomized controlled trial.
AB  - OBJECTIVE: We tested the hypothesis that direct intramyocardial injection of bone
      marrow mononuclear cells in patients with non-ischemic dilated cardiomyopathy can
      improve left ventricular function and physical capacity. METHODS: Thirty non
      ischemic dilated cardiomyopathy patients with left ventricular ejection fraction
      <35% were randomized at a 1:2 ratio into two groups, control and treated. The
      bone marrow mononuclear cells group received 1.06+/-108 bone marrow mononuclear
      cells through mini-thoracotomy. There was no intervention in the control group.
      Assessment was carried out through clinical evaluations as well as a 6-min walk
      test, nuclear magnectic resonance imaging and echocardiogram. RESULTS: The bone
      marrow mononuclear cells group showed a trend toward left ventricular ejection
      fraction improvement, with magnectic resonance imaging - at 3 months, showing an
      increase from 27.80+/-6.86% to 30.13+/-9.06% (P=0.08) and returning to baseline
      at 9 months (28.78%, P=0.77). Magnectic resonance imaging showed no changes in
      left ventricular ejection fraction during follow-up of the control group (28.00+/
      4.32%, 27.42+/-7.41%, and 29.57+/-4.50%). Echocardiogram showed left ventricular
      ejection fraction improved in the bone marrow mononuclear cells group at 3
      months, 25.09+/-3.98 to 30.94+/-9.16 (P=0.01), and one year, 30.07+/-7.25%
      (P=0.001). The control group showed no change (26.1+/-4.4 vs 26.5+/-4.7 and
      30.2+/-7.39%, P=0.25 and 0.10, respectively). Bone marrow mononuclear cells group
      showed improvement in New York Heart Association functional class, from 3.40+/
      0.50 to 2.41+/-0.79 (P=0.002); patients in the control group showed no change
      (3.37+/-0.51 to 2.71+/-0.95; P=0.17). Six-minute walk test improved in the bone
      marrow mononuclear cells group (348.00+/-93.51m at baseline to 370.41+/-91.56m at
      12 months, P=0.66) and there was a non-significant decline in the control group
      (361.25+/-90.78m to 330.00+/-123.42m after 12 months, P=0.66). Group comparisons
      were non-significant. CONCLUSION: The trend of intragroup functional and
      subjective improvement was not confirmed when compared to the control group.
      Direct intramyocardial application of bone marrow mononuclear cells in non
      ischemic dilated cardiomyopathy was not associated with significant changes in
      left ventricular function. Differences observed within the bone marrow
      mononuclear cells group could be due to placebo effect or low statistical power.

PMID- 25372921
TI  - Congenital cardiac disease in childhood x socioeconomic conditions: a
      relationship to be considered in public health?
AB  - INTRODUCTION: Congenital heart defects, cardiac malformations that occur in the
      embryonic period, constitute a serious health problem. They cover a proportion of
      8-10 per 1000 live births and contribute to infant mortality. OBJECTIVE: To
      identify the socioeconomic status of children undergoing cardiac surgery at the
      Hospital Universitario da Universidade Federal do Maranhao, in Sao Luis, the
      existence of material elements that contribute to worsening conditions. METHODS:
      We conducted a retrospective study with a quantitative approach, descriptive and
      reflective, from the interviews conducted by the Social Service Social with
      families of children with heart disease from January 2011 to July 2012. RESULTS:
      A total of 95 interviews, the results reveal that (75.79%) of children have
      elements that suggest poor socioeconomic conditions. It also shows that only
      66.33% lived in brick house, while (31.73%) in mud, adobe and straw houses. With
      regard to income, it showed that only 4.08% received 1-2 minimum wages, while the
      remaining (95.9%) with benchmarks oscillating half the minimum wage (27.55%), 1/4
      of the minimum wage and (24.48%) and income below 70 dollars per person,
      featuring extreme poverty. On the social security situation prevailing at
      children with no ties to 61.22%. With respect to benefits, we found that only
      (12.24%) of children were in the enjoyment of the Continuous Cash Benefit - CCB.
      CONCLUSION: Poor socioeconomic conditions listed as major obstacles in meeting
      the needs, resulting in the maintenance of health conditions and even allowing
      the aggravation of an existing pathology.

PMID- 25372922
TI  - Avoiding pitfalls of intraoperative peripheral endovascular surgery with the aid
      of OsiriX: expanding the use of virtual fluoroscopy.
AB  - We have shown how the analysis of the angiotomography reconstruction through
      OsiriX program has assisted in endovascular perioperative programming. We
      presented its application in situations when an unexpected existence of metallic
      overlapping artifact (orthopedic osteosynthesis) compromised the adequate
      visualization of the arterial lesion during the procedure. Through manipulation
      upon OsiriX software, with assistance of preview under virtual fluoroscopy, it
      was possible to obtain the angles that would avoid this juxtaposition. These
      angles were reproduced in the C-arm, allowing visualization of the occluded
      segment, reducing the need for repeated image acquisitions and contrast overload,
      allowing the continuation of the procedure. 

PMID- 25372924
TI  - Psychological assessment before heart transplantation: more hope to candidates in
      Brazil?

PMID- 25372923
TI  - New technique "Right Anterior Small Thoracotomy (RAST operation)" for beating
      heart grafting of the right internal thoracic artery to the posterior descending
      artery to the posterior descending artery in a third redo CABG patient. A novel
      coronary technique.
AB  - Third REDO-CABG is a challenge for the surgical team. Usually a patent mammary is
      the only graft working and the sternotomy becomes a risky procedure. Injury to a
      patent graft has been associated to a high mortality rate. Many different
      approaches have been proposed. We describe a novel technique to approach the
      right coronary artery through a right anterior small thoracotomy using the right
      mammary prolonged with saphenous vein for grafting the posterior descending
      artery on the beating heart. The technique is very simple and feasible because
      anatomically the right coronary artery and the right mammary are very close and
      the mobilization of the heart is minimal. 

PMID- 25372925
TI  - Police culture influences the brain function underlying compassion: a gender
      study.
AB  - Compassion is a prototypical moral emotion supporting cooperation and involves
      empathic decision-making and motor processes representing the interplay of
      biologically evolved and cultural mechanisms. We propose a social neuroscience
      approach to identify gender differences and to assess biological and cultural
      factors shaping compassion. We consider the police force as a cultural model to
      study this emotion, because it comprises a mixed-gender group using specific
      codes for collective safety that influence empathy and cooperativeness. From a
      sample of Mexican police officers working in a violent environment we integrated
      ethnographic data categorizing compassionate elements in the officers'
      activities, psychometric measures evaluating empathic attitudes, and fMRI scans
      identifying the brain activity related to compassionate experiences and
      decisions. The results suggest that the police culture influences genders equally
      with respect to empathic behavioral expressions. Nevertheless, women showed
      insular and prefrontal cortical activation, suggesting a more empathic experience
      of compassion. Officers manifested activity in the caudate nucleus, amygdala, and
      cerebellum, suggesting a more a highly accurate process to infer another's
      suffering and a reward system motivated by the notion of service and cooperation,
      both of which are cultural traits represented in the police force. 

PMID- 25372926
TI  - Long-lived charge separation in a rigid pentiptycene bis(crown ether)-Li(+)@C60
      host-guest complex.
AB  - We report long-lived charge separation in a highly rigid host-guest complex of
      pentiptycene bis(crown ether) and Li(+)@C60, in which the pentiptycene framework
      is actively involved as an electron donor in a photoinduced electron-transfer
      process to the excited states of Li(+)@C60 through a rigid distance in the
      complex. 

PMID- 25372928
TI  - Containing U.S. health care costs: What bullet to bite?
AB  - In this article, the authors provide an overview of the problem of health care
      cost containment. Both the growth of health care spending and its underlying
      causes are discussed. Further, the authors define cost containment, provide a
      framework for describing cost-containment strategies, and describe the major cost
      containment strategies. Finally, the role of research in choosing such a strategy
      for the United States is examined.

PMID- 25372927
TI  - Molecular evolution of the porcine type I interferon family: subtype-specific
      expression and antiviral activity.
AB  - Type I interferons (IFNs), key antiviral cytokines, evolve to adapt with ever
      changing viral threats during vertebrate speciation. Due to novel pathogenic
      pressure associated with Suidae speciation and domestication, porcine IFNs
      evolutionarily engender both molecular and functional diversification, which have
      not been well addressed in pigs, an important livestock species and animal model
      for biomedical sciences. Annotation of current swine genome assembly Sscrofa10.2
      reveals 57 functional genes and 16 pseudogenes of type I IFNs. Subfamilies of
      multiple IFNA, IFNW and porcine-specific IFND genes are separated into four
      clusters with ~ 60 kb intervals within the IFNB/IFNE bordered region in SSC1, and
      each cluster contains mingled subtypes of IFNA, IFNW and IFND. Further curation
      of the 57 functional IFN genes indicates that they include 18 potential
      artifactual duplicates. We performed phylogenetic construction as well as
      analyses of gene duplication/conversion and natural selection and showed that
      porcine type I IFN genes have been undergoing active diversification through both
      gene duplication and conversion. Extensive analyses of the non-coding sequences
      proximal to all IFN coding regions identified several genomic repetitive elements
      significantly associated with different IFN subtypes. Family-wide studies further
      revealed their molecular diversity with respect to differential expression and
      restrictive activity on the resurgence of a porcine endogenous retrovirus. Based
      on predicted 3-D structures of representative animal IFNs and inferred activity,
      we categorized the general functional propensity underlying the structure
      activity relationship. Evidence indicates gene expansion of porcine type I IFNs.
      Genomic repetitive elements that associated with IFN subtypes may serve as
      molecular signatures of respective IFN subtypes and genomic mechanisms to mediate
      IFN gene evolution and expression. In summary, the porcine type I IFN profile has
      been phylogenetically defined family-wide and linked to diverse expression and
      antiviral activity, which is important information for further biological studies
      across the porcine type I IFN family.

PMID- 25372929
TI  - Discrete nanoparticle-BSA conjugates manipulated by hydrophobic interaction.
AB  - Nanoparticle-protein conjugates are promising probes for biological diagnostics
      as well as versatile building blocks for nanotechnology. Here we demonstrate a
      facile method to prepare nanoparticles bearing discrete numbers of BSA simply by
      physical adsorption and electrophoretic isolation, in which the specific
      amphiphilic properties of BSA play important roles and the number of adsorbed BSA
      molecules can also be manipulated by tuning the coating extent of nanoparticles
      by amphiphilic polymer. 

PMID- 25372930
TI  - Semiconducting polymers with nanocrystallites interconnected via boron-doped
      carbon nanotubes.
AB  - Organic semiconductors are key building blocks for future electronic devices that
      require unprecedented properties of low-weight, flexibility, and portability.
      However, the low charge-carrier mobility and undesirable processing conditions
      limit their compatibility with low-cost, flexible, and printable electronics.
      Here, we present significantly enhanced field-effect mobility (MU(FET)) in
      semiconducting polymers mixed with boron-doped carbon nanotubes (B-CNTs). In
      contrast to undoped CNTs, which tend to form undesired aggregates, the B-CNTs
      exhibit an excellent dispersion in conjugated polymer matrices and improve the
      charge transport between polymer chains. Consequently, the B-CNT-mixed
      semiconducting polymers enable the fabrication of high-performance FETs on
      plastic substrates via a solution process; the MUFET of the resulting FETs
      reaches 7.2 cm(2) V(-1) s(-1), which is the highest value reported for a flexible
      FET based on a semiconducting polymer. Our approach is applicable to various
      semiconducting polymers without any additional undesirable processing treatments,
      indicating its versatility, universality, and potential for high-performance
      printable electronics.

PMID- 25372931
TI  - Access to Care for Disabled Children Under Medicaid.
AB  - This article examines differences in access and use of care among children on
      Medicaid with physical disabilities, mental illness, and mental
      retardation/development disabilities (MR/DD) in New York City (NYC). We use 1999
      and 2000 survey data obtained from the parents of a random sample of disabled
      children on Medicaid to conduct both descriptive and multivariate analyses. We
      find that the Medicaid Program has been successful at linking disabled children
      to health care providers. However, there is evidence of greater access problems
      for some subgroups of disabled children. Improving access for disabled children
      under the Medicaid Program will require targeted help to specific groups of
      children.

PMID- 25372932
TI  - Genetic polymorphism of matrix metalloproteinase-1 and coronary artery disease
      susceptibility: a case-control study in a Han Chinese population.
AB  - Coronary artery disease (CAD) receives intensive research due to its high
      incidence and severe impact on the quality of life. One member of the matrix
      metalloproteinases (MMPs), MMP-1, has been reported to be associated with CAD. To
      identify the markers contributing to the genetic susceptibility to CAD, nine
      single-nucleotide polymorphisms (rs1799750, rs498186, rs475007, rs514921,
      rs494379, rs996999, rs2071232, rs1938901, and rs2239008) throughout the MMP-1
      gene were genotyped using MALDI-TOF within the MassARRAY system, and the allele
      and genotype distributions were compared between 438 healthy controls and 411
      patients with CAD from a Chinese Han population. The analysis revealed a weak
      association between the rs1799750 (in the promoter region) genotype distribution
      and CAD (p=0.022). An increased risk of CAD was significantly associated with the
      2G allele of rs1799750 (p=0.005, odds ratio=1.329, 95% confidence interval=1.090
      1.620, after Bonferroni corrections). Strong linkage disequilibrium was observed
      in three blocks (D'>0.9). Significantly more C-2G (rs498186-rs1799750) haplotypes
      (p=0.001 after Bonferroni corrections) were found in CAD subjects. These findings
      point to a role for the polymorphism in the MMP-1 promoter in CAD among a Han
      Chinese population and may be informative for future genetic or biological
      studies on CAD. 

PMID- 25372933
TI  - The photochemistry of inverse dithienylethene switches understood.
AB  - The photophysical properties of a series of dithienylethenes, free or blocked in
      an ideal photoactive conformation by an alkyl bridge, have been investigated by
      stationary, ultrafast spectroscopy and state-of-the-art time-dependent density
      functional theory calculations. Thanks to the clear ultrafast transient
      signatures corroborating NMR results, we bring strong evidence that the
      unreactive parallel open form conformer has been efficiently removed by the
      chain. For the first time, the photophysics of this species, namely an internal
      conversion of 120 ps is highlighted. In contradiction to the main ideas in the
      literature, the photocyclization mechanism is rationalized by a direct
      photocyclization mechanism from the Franck-Condon region passing directly through
      a conical intersection within ~100 fs (not few picoseconds) while a competitive
      mechanism occurs through the relaxed S1 state. Relaxation processes (fluorescence
      and internal conversion) originating from this relaxed state are sensitive to the
      length of the blocking chain. Both concomitant pathways are necessary to
      rationalize: (i) the inverse relationship between emission and cyclization
      quantum yields and (ii) the non-unity value of the latter for bridged compounds. 

PMID- 25372934
TI  - Case-mix measurement and assessing quality of hospital care.

PMID- 25372936
TI  - Health Care Indicators.
AB  - THIS REGULAR FEATURE OF THE JOURNAL INCLUDES A DISCUSSION OF EACH OF THE
      FOLLOWING FOUR TOPICS: community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25372935
TI  - Initial severity of schizophrenia and efficacy of antipsychotics: participant
      level meta-analysis of 6 placebo-controlled studies.
AB  - IMPORTANCE: Antipsychotic drugs constitute the mainstay in the treatment of
      schizophrenia, and their efficacy is well established in hundreds of randomized
      clinical trials. However, it is not known whether they are effective or how
      effective they are across the wide range of baseline symptom severity. OBJECTIVE:
      To examine the influence of baseline severity of schizophrenia on the efficacy of
      antipsychotic drugs. DESIGN, SETTING, AND PARTICIPANTS: Meta-analysis of
      participant-level data from 3 pivotal randomized trials of acute schizophrenia (n
      = 611) and 3 pivotal trials in patients with predominantly negative symptoms of
      schizophrenia (n = 475). INTERVENTIONS: Olanzapine or risperidone vs placebo, and
      amisulpride vs placebo. MAIN OUTCOMES AND MEASURES: Change scores on the Positive
      and Negative Syndrome Scale (PANSS; score range, 30-210) and the Scale for the
      Assessment of Negative Symptoms (SANS; score range, 0-125) up to 6 weeks after
      baseline. The relationship between baseline and change scores for the drug and
      placebo groups was examined with 8 competing mixed-effects models for repeated
      measures. RESULTS: The best-fitting models showed that, for both types of
      patients, the interactions between baseline symptom severity and treatment were
      statistically significant (P < .01). The greater the baseline severity was, the
      greater the magnitude of the differences was between active treatment and
      placebo. In acute treatment, the mean differences in PANSS change scores were 9.5
      points for patients who were mildly ill at baseline (baseline PANSS score of 58),
      13.7 for moderately ill patients (baseline PANSS score of 75), 18.8 for markedly
      ill patients (baseline PANSS score of 95), and 24.0 for severely ill patients
      (baseline PANSS score of 116). In treatment of predominantly negative symptoms,
      the mean differences in SANS change scores were 1.7 for those who were moderately
      ill (baseline SANS score of 55), 5.7 for markedly ill patients (baseline SANS
      score of 70), and 9.7 for severely ill patients (baseline SANS score of 85).
      CONCLUSIONS AND RELEVANCE: We can expect benefits of antipsychotic drugs for the
      full spectrum of patients likely to be treated for acute schizophrenia and for
      highly symptomatic patients with predominantly negative symptoms. Toward the
      mildest end of the spectrum, clinicians need to be aware that patients benefit
      less in terms of symptom improvement but may experience full adverse effects of
      antipsychotics. Clinicians also need to be aware that in addition to the
      treatment of active symptoms, which was the focus of this study, antipsychotics
      have another important action, namely to prevent relapses among patients in
      remission.

PMID- 25372937
TI  - Local and nonlocal optically induced transparency effects in graphene-silicon
      hybrid nanophotonic integrated circuits.
AB  - Graphene is well-known as a two-dimensional sheet of carbon atoms arrayed in a
      honeycomb structure. It has some unique and fascinating properties, which are
      useful for realizing many optoelectronic devices and applications, including
      transistors, photodetectors, solar cells, and modulators. To enhance light
      graphene interactions and take advantage of its properties, a promising approach
      is to combine a graphene sheet with optical waveguides, such as silicon
      nanophotonic wires considered in this paper. Here we report local and nonlocal
      optically induced transparency (OIT) effects in graphene-silicon hybrid
      nanophotonic integrated circuits. A low-power, continuous-wave laser is used as
      the pump light, and the power required for producing the OIT effect is as low as
      ~0.1 mW. The corresponding power density is several orders lower than that needed
      for the previously reported saturated absorption effect in graphene, which
      implies a mechanism involving light absorption by the silicon and photocarrier
      transport through the silicon-graphene junction. The present OIT effect enables
      low power, all-optical, broadband control and sensing, modulation and switching
      locally and nonlocally. 

PMID- 25372938
TI  - Genetics of superionic conductivity in lithium lanthanum titanates.
AB  - The self-diffusion of ions is a fundamental mass transport process in solids and
      has a profound impact on the performance of electrochemical devices such as the
      solid oxide fuel cell, batteries and electrolysers. The perovskite system lithium
      lanthanum titanate, La2/3-xLi3xTiO3 (LLTO) has been the subject of much academic
      interest as it displays very high lattice conductivity for a solid state Li
      conductor; making it a material of great technological interest for deployment in
      safe durable mobile power applications. However, so far, a clear picture of the
      structural features that lead to efficient ion diffusion pathways in LLTO, has
      not been fully developed. In this work we show that a genetic algorithm in
      conjunction with molecular dynamics can be employed to elucidate diffusion
      mechanisms in systems such as LLTO. Based on our simulations we provide evidence
      that there is a three-dimensional percolated network of Li diffusion pathways.
      The present approach not only reproduces experimental ionic conductivity results
      but the method also promises straightforward investigation and optimisation of
      the properties relating to superionic conductivity in materials such as LLTO.
      Furthermore, this method could be used to provide insights into related materials
      with structural disorder. 

PMID- 25372939
TI  - Beneficiary Perspective.
AB  - This executive summary of Karen Davis' remarks was prepared by Julie Snyder of
      the University of Texas LBJ School of Public Affairs. The remarks were given in
      the context of a panel presentation moderated by Davis, entitled "Beneficiary
      Perspective."

PMID- 25372940
TI  - 2D perovskite nanosheets with thermally-stable high-kappa response: a new
      platform for high-temperature capacitors.
AB  - We investigated high-temperature dielectric responses of high-kappa perovskite
      nanosheet (Ca2Nb3O10), an important material platform for postgraphene technology
      and ultrascale electronic devices. Through in situ characterizations using
      conducting atomic force microscopy, we found a robust high-temperature property
      of Ca2Nb3O10 nanosheet even in a monolayer form (~2 nm). Furthermore, layer-by
      layer assembled nanocapacitors retained both size-free high-epsilonr
      characteristic (~200) and high insulation resistance (~1*10(-7) A/cm2) at high
      temperatures up to 250  degrees C. The simultaneous improvement of epsilonr and
      thermal stability in high-kappa nanodielectrics is of critical technological
      importance, and perovskite nanosheet has great potential for a rational design
      and construction of high-temperature capacitors.

PMID- 25372942
TI  - Predictive value of decoy receptor 3 in postoperative nosocomial bacterial
      meningitis.
AB  - Nosocomial bacterial meningitis requires timely treatment, but what is difficult
      is the prompt and accurate diagnosis of this disease. The aim of this study was
      to assess the potential role of decoy receptor 3 (DcR3) levels in the
      differentiation of bacterial meningitis from non-bacterial meningitis. A total of
      123 patients were recruited in this study, among them 80 patients being with
      bacterial meningitis and 43 patients with non-bacterial meningitis. Bacterial
      meningitis was confirmed by bacterial culture of cerebrospinal fluid (CSF)
      culture and enzyme-linked immunosorbent assay (ELISA) was used to detect the
      level of DcR3 in CSF. CSF levels of DcR3 were statistically significant between
      patients with bacterial meningitis and those with non-bacterial meningitis
      (p<0.001). A total of 48.75% of patients with bacterial meningitis received
      antibiotic>24 h before CSF sampling, which was much higher than that of non
      bacterial meningitis. CSF leucocyte count yielded the highest diagnostic value,
      with an area under the receiver operating characteristic curve (ROC) of 0.928,
      followed by DcR3. At a critical value of 0.201 ng/mL for DcR3, the sensitivity
      and specificity were 78.75% and 81.40% respectively. DcR3 in CSF may be a
      valuable predictor for differentiating patients with bacterial meningitis from
      those with non-bacterial meningitis. Further studies are needed for the
      validation of this study.

PMID- 25372941
TI  - Identification of protein markers in patients infected with Plasmodium knowlesi,
      Plasmodium falciparum and Plasmodium vivax.
AB  - Malaria is caused by parasitic protozoans of the genus Plasmodium and is one of
      the most prevalent infectious diseases in tropical and subtropical regions. For
      this reason, effective and practical diagnostic methods are urgently needed to
      control the spread of malaria. The aim of the current study was to identify a
      panel of new malarial markers, which could be used to diagnose patients infected
      with various Plasmodium species, including P. knowlesi, P. vivax and P.
      falciparum. Sera from malaria-infected patients were pooled and compared to
      control sera obtained from healthy individuals using the isobaric tags for
      relative and absolute quantitation (iTRAQ) technique. Mass spectrometry was used
      to identify serum proteins and quantify their relative abundance. We found that
      the levels of several proteins were increased in pooled serum from infected
      patients, including cell adhesion molecule-4 and C-reactive protein. In contrast,
      the serum concentration of haptoglobin was reduced in malaria-infected
      individuals, which we verified by western blot assay. Therefore, these proteins
      might represent infectious markers of malaria, which could be used to develop
      novel diagnostic tools for detecting P. knowlesi, P. vivax and P. falciparum.
      However, these potential malarial markers will need to be validated in a larger
      population of infected individuals. 

PMID- 25372943
TI  - Ultrasensitive imaging of Ca2+ dynamics in pancreatic acinar cells of yellow
      cameleon-nano transgenic mice.
AB  - Yellow Cameleons are genetically encoded Ca2+ indicators in which cyan and yellow
      fluorescent proteins and calmodulin work together as a fluorescence (Forster)
      resonance energy transfer Ca2+-sensor probe. To achieve ultrasensitive Ca2+
      imaging for low resting Ca2+ or small Ca2+ transients in various organs, we
      generated a transgenic mouse line expressing the highest-sensitive genetically
      encoded Ca2+ indicator (Yellow Cameleon-Nano 15) in the whole body. We then
      focused on the mechanism of exocytotic events mediated by intracellular Ca2+
      signaling in acinar cells of the mice with an agonist and observed them by two
      photon excitation microscopy. In the results, two-photon excitation imaging of
      Yellow Cameleon-Nano 15 successfully visualized intracellular Ca2+ concentration
      under stimulation with the agonist at nanomolar levels. This is the first
      demonstration for application of genetically encoded Ca2+ indicators to
      pancreatic acinar cells. We also simultaneously observed exocytotic events and an
      intracellular Ca2+ concentration under in vivo condition. Yellow Cameleon-Nano 15
      mice are healthy and no significant deteriorative effect was observed on
      physiological response regarding the pancreatic acinar cells. The dynamic range
      of 165% was calculated from Rmax and Rmin values under in vivo condition. The
      mice will be useful for ultrasensitive Ca2+ imaging in vivo. 

PMID- 25372944
TI  - ZmSOC1, a MADS-box transcription factor from Zea mays, promotes flowering in
      Arabidopsis.
AB  - Zea mays is an economically important crop, but its molecular mechanism of
      flowering remains largely uncharacterized. The gene, SUPPRESSOR OF OVEREXPRESSION
      OF CONSTANS 1 (SOC1), integrates multiple flowering signals to regulate floral
      transition in Arabidopsis. In this study, ZmSOC1 was isolated from Zea mays.
      Sequence alignment and phylogenetic analysis demonstrated that the ZmSOC1 protein
      contained a highly conserved MADS domain and a typical SOC1 motif. ZmSOC1 protein
      was localized in the nucleus in protoplasts and showed no transcriptional
      activation activity in yeast cells. ZmSOC1 was highly expressed in maize
      reproductive organs, including filaments, ear and endosperm, but expression was
      very low in embryos; on the other hand, the abiotic stresses could repress ZmSOC1
      expression. Overexpression of ZmSOC1 resulted in early flowering in Arabidopsis
      through increasing the expression of AtLFY and AtAP1. Overall, these results
      suggest that ZmSOC1 is a flowering promoter in Arabidopsis. 

PMID- 25372946
TI  - A facilitator of leisure activities for stress-related growth experience among
      middle-aged Korean women with depression.
AB  - Leisure may serve as a coping resource following negative life events that
      facilitate positive changes. Previous studies on leisure have mainly focused on
      stress-related growth among individuals living in Western cultures. This study
      aimed to capture the role of leisure involvement as a facilitator of stress
      related growth among middle-aged Korean women with depression. Three main themes
      were identified as an outcome of participation in leisure activities: (a)
      strengthening meaningful relationships, (b) improving positive emotions, and (c)
      facilitating personal strength. By participating in leisure activities,
      individuals with depression may develop the ability to cope with stress and
      experience positive changes. 

PMID- 25372945
TI  - Validation of Bmi1 as a therapeutic target of hepatocellular carcinoma in mice.
AB  - Bmi1 is a member of the polycomb group family of proteins, and it drives the
      carcinogenesis of various cancers and governs the self-renewal of multiple types
      of stem cells. Our previous studies have revealed that Bmi1 acts as an oncogene
      in hepatic carcinogenesis in an INK4a/ARF locus independent manner. However,
      whether Bmi1 can be used as a potential target for hepatocellular carcinoma
      treatment has not been fully confirmed yet. Here, we show that perturbation of
      Bmi1 expression by using short hairpin RNA can inhibit the tumorigenicity and
      tumor growth of hepatocellular carcinoma cells both in vitro and in vivo.
      Importantly, Bmi1 knockdown can block the tumor growth, both in the initiating
      stages and the fast growing stages. Cellular biology analysis revealed that Bmi1
      knockdown induces cell cycle arrest and apoptosis. Our findings verify Bmi1 as a
      qualified treatment target for hepatocellular carcinoma (HCC) and support Bmi1
      targeting treatment with chemotherapeutic agents. 

PMID- 25372947
TI  - Panic, paranoia, and public health--the AIDS epidemic's lessons for Ebola.

PMID- 25372948
TI  - Ligand-centered redox in nickel(II) complexes of 2-(arylazo)pyridine and
      isolation of 2-pyridyl-substituted triaryl hydrazines via catalytic N-arylation
      of azo-function.
AB  - A series of nickel complexes of 2-(arylazo)pyridine have been synthesized, and
      the precise structure and stoichiometry of the complexes are controlled by the
      use of different metal precursors. Molecular and electronic structures of the
      isolated complexes are scrutinized thoroughly by various spectroscopic
      techniques, single crystal X-ray crystallography, and density functional theory
      (DFT). Two different classes of Ni(II) complexes are identified where the ligands
      bind as neutral or anion radicals in the respective metal complexes. These are
      shown to be chemically interconvertible, and their characterization confirmed
      that the redox series is entirely ligand-centered without affecting the bivalent
      oxidation state of the metal ion. An efficient method of Ni(II) catalyzed N
      arylation of 2-(arylazo)pyridine substrates has been elaborated. The chemical
      reactions have led to isolation of strongly fluorescent 2-pyridyl-substituted
      hydrazine derivatives, which have been characterized thoroughly. Three
      dimensional X-ray structure of a hydrazine molecule, 2-(2-(naphthalen-1-yl)-2
      phenylhydrazinyl)pyridine, is reported. Isolated hydrazines satisfy all the
      prerequisites of an ideal dye with moderate absorptive property, large Stokes
      shift, high quantum yields, and high photostability. 

PMID- 25372949
TI  - Static magnetic field inhibits 5' nucleotidase activity in cancerous and non
      cancerous human gastric tissues.
AB  - The aim of the present study is to investigate possible effects of static
      magnetic field (SMF) on 5' nucleotidase (5'NT-CD73) and xanthine oxidase (XO)
      activities in cancerous and non-cancerous human gastric tissues in order to
      contribute to the elucidation of the anticancer activity of SMF. Cancerous and
      non-cancerous human gastric tissues removed from patients by surgical operations
      were used in the studies. SMF was created using two static magnets. Before and
      after treatment with SMF, 5'NT and XO activities in the tissue samples were
      measured. 5'NT activity was found to be lowered, but no significant change was
      observed in XO activity in the gastric tissues treated with the SMF. Our results
      suggest that SMF inhibits 5'NT enzyme in gastric tissues significantly. It is
      supposed that in addition to other proposed mechanisms, inhibition of purine
      catabolic activity due to inhibition of some key enzymes in the DNA turn-over
      like 5'NT might also play part in the anticancer activity of SMF. 

PMID- 25372950
TI  - Sequentially updating the likelihood of success of a Phase 3 pivotal time-to
      event trial based on interim analyses or external information.
AB  - When performing a pivotal clinical trial, it may be of interest to assess the
      probability of success (PoS) of that trial. Initially evaluated when the trial is
      designed, PoS can be updated as the trial progresses and new information about
      the drug effect becomes available. Such information can be external to the trial,
      such as results from trials conducted in parallel, or internal, such as
      continuing after an interim analysis. We develop a framework to update PoS based
      on such internal and external information for a time-to-event endpoint and
      illustrate it using a realistic development program for a new molecule. 

PMID- 25372954
TI  - Enhancing the stability of lipid nanoparticle systems by sonication during the
      cooling step and controlling the liquid oil content.
AB  - Aggregation of unstable particles in water limits the application of lipid
      nanoparticle (LNP) systems to foods despite the capability to encapsulate
      lipophilic bioactive components. This study exploits a preparation process that
      can reduce the aggregation of LNPs. Sonication during the cooling step
      (postsonication) for 4, 5, or 6 min was applied to increase the covering effect
      of Tween 20 on the particle. Additionally, LNPs were prepared using fully
      hydrogenated canola oil (FHCO) blended with 0-30 wt % liquid canola oil (LCO) of
      the lipid phase. Surfactant surface load data indicate that the postsonication
      might make nonemulsifying Tween 20 diffuse from the aqueous phase to droplet
      surfaces, which could decrease the crystallinity index (CI) of LNPs due to the
      inhibition of lipid crystallization. Moreover, the LCO content in lipid matrix
      could decrease the CI, which could reduce the formation of hydrophobic patches on
      the particle surface. Therefore, the postsonication and the LCO addition in the
      matrix could effectively prevent aggregation among hydrophobic patches. This
      improved colloidal stability of LNPs was verified by the particle shape in
      transmission electron microscopy and the gelation test. Consequently, LNPs
      fabricated using 6 min postsonication and 30 wt % LCO in the lipid exhibited the
      greatest stability (size, 202.3 nm; CI, 57.5%; Tween 20 surface load, 10.29 mg m(
      2)). This study may serve as a basis for further research that aims to develop
      delivery systems for functional foods. 

PMID- 25372955
TI  - Distance-dependent fluorescence of tris(bipyridine)ruthenium(II) on supported
      plasmonic gold nanoparticle ensembles.
AB  - Metal surfaces and nanostructures interact with fluorescent materials, enhancing
      or quenching the fluorescence intensity, modifying the fluorescent lifetime, and
      changing the emission frequency and linewidth. These interactions occur via
      several mechanisms, including radiationless energy transfer, electric field
      enhancement, and photonic mode density modification. The interactions display a
      strong dependence on the distance between the fluorophore and the metal
      structures. Here we study the distance-dependent effects of two types of
      plasmonic gold nano-island films on the emission intensity, wavelength, linewidth
      and lifetime of a fluorophore layer, separated from the film by a dielectric
      spacer 2-348 nm thick. The distance dependence is found to be unrelated to the
      plasmonic field decay lengths. In some cases fluorescence intensity enhancement
      is seen even at 200 nm metal-fluorophore separation, indicating far-field
      effects. We report, for the first time, a distance-dependent oscillation in the
      emission peak wavelength and linewidth, attributed to interference-based
      oscillations in the intensity of the electric field. We find that the studied
      nanoparticle (NP) films do not display the previously reported distance profile
      of single NPs, but rather behave in a collective fashion similar to continuous
      metal surfaces. 

PMID- 25372957
TI  - Health Care for the Poor: Medicaid at 35.
AB  - Over its 35-year history, Medicaid has grown from a program to provide health
      insurance to the welfare population to one that provides health and long-term
      care (LTC) services to 40 million low-income families and elderly and disabled
      individuals. Despite its accomplishments in improving access to health care for
      low-income populations, Medicaid continues to face many challenges. The future of
      Medicaid as our Nation's health care safety net will be determined by Medicaid's
      ability to broaden health coverage for the low-income uninsured, secure access to
      quality care for its growing beneficiary population, and manage costs between the
      Federal and State governments.

PMID- 25372959
TI  - Errata.
AB  - [This corrects the article on p. 111 in vol. 10, PMID: 10313274.].

PMID- 25372958
TI  - Medicaid Managed Care and Racial Disparities in AIDS Treatment.
AB  - The study compares racial differences in access to highly active antiretroviral
      therapy (HAART) for human immunodeficiency virus (HIV) patients under Medicaid
      managed care and Medicaid fee-for-service (FFS). This study uses the HIV Cost and
      Services Utilization Study (HCSUS) data set. The analysis includes Black and
      White Medicaid enrollees with HIV/AIDS in 1996. Logistic regression is used to
      estimate the models with exposure to HAART as the dependent variable. This study
      suggests that Black enrollees still face barriers in access to care, even after
      Medicaid has assured financial access. Disparities in access to HIV/AIDS
      treatment exist under both Medicaid FFS and Medicaid managed care.

PMID- 25372960
TI  - Developing Performance Measures for Prescription Drug Management.
AB  - Prescription drug management plans are outpatient drug benefit programs that
      strive to manage the cost effective and clinically appropriate delivery of
      prescription drugs to beneficiaries. The demand for accountability and a means to
      evaluate performance of drug benefit management programs is growing;
      nevertheless, a set of valid, standardized indicators for evaluating performance
      does not exist. We review drug management program activities and identify
      available measures for assessing performance. Additionally, we note recent
      efforts to develop performance indicators for prescription drug management. We
      conclude by raising key questions that should be addressed before a comprehensive
      set of performance measures can be implemented.

PMID- 25372961
TI  - Further consideration of Advanced Clinical Solutions Word Choice: comparison to
      the Recognition Memory Test-words and classification accuracy in a clinical
      sample.
AB  - Word Choice (WC), a test in the Advanced Clinical Solutions package for Wechsler
      measures, was examined in two studies. The first study compared WC to the
      Recognition Memory Test-Words (RMT-W) in a clinical sample (N = 46). WC scores
      were significantly higher than RMT-W scores overall and in sample subsets grouped
      by separate validity indicators. In item-level analyses, WC items demonstrated
      lower frequency, greater imageability, and higher concreteness than RMT-W items.
      The second study explored WC classification accuracy in a different clinical
      sample grouped by separate validity indicators into Pass (n = 54), Fail-1 (n =
      17), and Fail-2 (n = 8) groups. WC scores were significantly higher in the Pass
      group (M = 49.1, SD = 1.9) than in the Fail-1 (M = 46.0, SD = 5.3) and Fail-2 (M
      = 44.1, SD = 4.8) groups. WC demonstrated area under the curve of .81 in
      classifying Pass and Fail-2 participants. Using the test manual cutoff associated
      with a 10% false positive rate, sensitivity was 38% and specificity was 96% in
      Pass and Fail-2 groups with 24% of Fail-1 participants scoring below cutoff. WC
      may be optimally used in combination with other measures given observed
      sensitivity. 

PMID- 25372962
TI  - Children's Preventive Care Use Under Two Mature Medicaid Managed Care Plans in
      California.
AB  - We investigated the extent to which children continuously enrolled in two mature
      county-organized Medicaid managed care plans for 6, 12, and 24 months received
      recommended well-child visits and immunizations. We also investigated whether any
      improvements in compliance were evident during the period 1989-92. Compliance was
      low for well-child visits and immunizations at the recommended ages regardless of
      eligibility group. Although slight improvements in immunizations were made over
      time, little progress was made in compliance with well-child visits. Continued
      vigilance is required to achieve the government's goal of 90 percent immunization
      compliance among 2-year-olds.

PMID- 25372963
TI  - Posaconazole treatment of extensive skin and nail dermatophytosis due to
      autosomal recessive deficiency of CARD9.
AB  - IMPORTANCE: Deep dermatophytosis is a disease that involves dermatophytic
      infection of the dermis and/or lymph nodes and sometimes the central nervous
      system. Autosomal recessive deficiency of the CARD9 (caspase recruitment domain
      9) protein has been described in 17 patients with deep dermatophytosis from
      Algeria, Tunisia, and Morocco. OBSERVATIONS: We report a case of extensive
      dermatophytosis due to autosomal recessive CARD9 deficiency in a patient of
      Egyptian origin. This patient had extensive superficial Trichophyton rubrum
      infection of the skin and nails without significant visceral involvement.
      Treatment with posaconazole was well tolerated and induced a complete clinical
      remission within 3 months that continued for 8 months of follow-up. CONCLUSIONS
      AND RELEVANCE: This case report underlines the phenotypic variability of
      dermatophytic infection in patients with CARD9 deficiency and the potential
      efficacy of posaconazole for this indication.

PMID- 25372964
TI  - Studying BME in the United Kingdom.
AB  - In the United Kingdom, the field of engineering in biology and medicine is so new
      that universities cannot agree on what to call it or even where to teach it.
      Undergraduate students in the United Kingdom can register for degrees in
      bioengineering, biomedical engineering, medical engineering, clinical
      engineering, medical physics, or even rehabilitation engineering; and these could
      be taught in specialist institutions, mechanical and electronic engineering
      departments, medical schools and hospitals, or even by distance learning. 

PMID- 25372965
TI  - A view from the outside in.
AB  - This paper discusses the use of imaging modalities such as CT, MRI and ultrasound
      imaging in intervention therapy, surgery and drug delivery. The paper points how
      these image-guided therapies are quickly becoming a foundation of medical care. 

PMID- 25372966
TI  - Image-guided therapies.
AB  - This paper presents image-guided therapies development and advantages using real
      time imaging modalities such as computed tomography, ultrasound imaging, and
      magnetic resonance imaging. The following are also highlighted: image-guided
      cancer interventions and image-guided cardiovascular interventions. 

PMID- 25372967
TI  - Thermal tumor ablation in clinical use.
AB  - Although a surgical procedure is performed by visual inspection with
      histopathological assessment of the excised tumor and margins, percutaneous and
      noninvasive thermal ablation is performed strictly with the aid of imaging.
      Applicator guidance into the target zone, treatment monitoring and verification,
      and clinical follow-up rely on effective imaging. Detailed discussion of imaging
      is beyond the scope of this article, but the influence of imaging on the choice
      of thermal ablation or procedural approach will be discussed as needed. More
      information on imaging for interventional therapies can be found in other
      articles in this issue of IEEE Pulse. 

PMID- 25372968
TI  - MRI-controlled ultrasound thermal therapy.
AB  - Advances in medical imaging have enabled the development of new minimally and
      completely noninvasive therapies that produce a desired biological effect in a
      target, such as a tumor, with minimal damage to the surrounding tissue. One means
      of noninvasively achieving bioeffects in tissue is the use of ultrasound to
      generate heat. Specialized ultrasound transducers can be used to generate focal
      regions of heating non invasively, without inserting anything into the body or
      affecting the tissue outside the target region. Ultrasound thermal therapy can be
      used with magnetic resonance (MR) imaging (MRI) guidance and MRI temperature
      feedback to automatically control temperature distributions during heating,
      producing accurate thermal lesions, or maintaining optimal conditions to enhance
      drug delivery. 

PMID- 25372969
TI  - Planning of image-guided interventions in the liver.
AB  - In the following, we demonstrate the use of computational modeling for treatment
      planning of interventional procedures on the example of two clinically used
      therapies for liver cancer, which are used for both primary tumors (i.e., cancer
      originating in the liver) as well as metastatic tumors. 

PMID- 25372970
TI  - Contrast echocardiography for cardiac radio-frequency ablation.
AB  - The authors presented a first application of 2-D contrast-enhanced ICE in
      localizing RF ablation lesions and, more importantly, accurately and reproducibly
      quantifying their extent and depth within the myocardium in the intact beating
      heart. Furthermore, the study extended this application and presented, for the
      first time, a novel method based on contrast-enhanced 3-D ICE to describe details
      of contiguous linear lesions. 

PMID- 25372971
TI  - Oxygen tension variation in ischemic gastrocnemius muscle, marrow, and different
      hypoxic conditions in vitro.
AB  - BACKGROUND: Bone marrow stromal cells (BMSCs) play an important role in ischemic
      limb angiogenesis. BMSCs cultured in vitro can be exposed to oxygen tension much
      higher than that experienced in vivo. This study assessed oxygen tension in bone
      marrow and ischemic muscle in vivo, and then identified an appropriate oxygen
      concentration for culturing BMSCs. MATERIAL/METHODS: Unilateral hind limb
      ischemia was surgically induced in 30 mice, and tissue oxygen tension in
      bilateral gastrocnemius muscles and femoral bone marrow was monitored in vivo
      using a micro-electrode at 24 hours, 1 week, 2 weeks, and 3 weeks after modeling.
      Media used for culturing normal marrow, muscle, and artery tissue were incubated
      with various oxygen concentrations, and O2 tension was continuously monitored.
      Oxygen tension in aortic arterial blood was monitored using a micro-electrode and
      blood gas analyzer, and the results were compared. RESULTS: Oxygen tension in
      ischemic gastrocnemius muscle reached a nadir at 1 week after ischemic modeling,
      when histological changes were most noticeable. Culture media incubated with 3%,
      6%, and 14% oxygen (the normal oxygen levels of bone marrow, muscle, and arterial
      blood, respectively) required 9, 6, and 2 hours, respectively, to reach an
      equilibrated oxygen tension, and oxygen tension was elevated by 1.6-, 1.2-, and
      0.4-fold, respectively, upon re-exposure of the media to air. CONCLUSIONS:
      Physiological oxygen tension differs in different tissues. A 3% O2 concentration
      mimics the physiological O2 exposure experienced by BMSCs and represents the
      hypoxic concentration. Culture medium incubated under hypoxic conditions requires
      a prolonged period of time to regain equilibrated oxygen tension.

PMID- 25372972
TI  - Irreversible catalyst activation enables hyperpolarization and water solubility
      for NMR signal amplification by reversible exchange.
AB  - Activation of a catalyst [IrCl(COD)(IMes)] (IMes = 1,3-bis(2,4,6
      trimethylphenyl)imidazol-2-ylidene; COD = cyclooctadiene)] for signal
      amplification by reversible exchange (SABRE) was monitored by in situ
      hyperpolarized proton NMR at 9.4 T. During the catalyst-activation process, the
      COD moiety undergoes hydrogenation that leads to its complete removal from the Ir
      complex. A transient hydride intermediate of the catalyst is observed via its
      hyperpolarized signatures, which could not be detected using conventional
      nonhyperpolarized solution NMR. SABRE enhancement of the pyridine substrate can
      be fully rendered only after removal of the COD moiety; failure to properly
      activate the catalyst in the presence of sufficient substrate can lead to
      irreversible deactivation consistent with oligomerization of the catalyst
      molecules. Following catalyst activation, results from selective RF-saturation
      studies support the hypothesis that substrate polarization at high field arises
      from nuclear cross-relaxation with hyperpolarized (1)H spins of the
      hydride/orthohydrogen spin bath. Importantly, the chemical changes that
      accompanied the catalyst's full activation were also found to endow the catalyst
      with water solubility, here used to demonstrate SABRE hyperpolarization of
      nicotinamide in water without the need for any organic cosolvent--paving the way
      to various biomedical applications of SABRE hyperpolarization methods.

PMID- 25372973
TI  - Osmotically-driven transport in carbon nanotube porins.
AB  - We report the measurements of transport of ions and uncharged species through
      carbon nanotube (CNT) porins--short segments of CNTs inserted into a lipid
      bilayer membrane. Rejection characteristics of the CNT porins are governed by
      size exclusion for the uncharged species. In contrast, rejection of ionic species
      is governed by the electrostatic repulsion and Donnan membrane equilibrium.
      Permeability of monovalent cations follows the general trend in the hydrated ion
      size, except in the case of Cs(+) ions.

PMID- 25372977
TI  - Research Issues: Dually Eligible Medicare and Medicaid Beneficiaries, Challenges
      and Opportunities.
AB  - This overview describes the Medicare and Medicaid dually eligible beneficiaries,
      and it summarizes challenges in obtaining information and designing health care
      and supportive systems across the continuum of their needs. Some of the
      challenges include: the complexities of Medicaid eligibility, key structural
      differences between Medicare and Medicaid, long-standing data limitations, and
      determining appropriate payment mechanisms and amounts. The overview discusses
      and highlights changes that are expected to improve the potential for research on
      dual eligible issues.

PMID- 25372978
TI  - Overview.
AB  - This issue of the Health Care Financing Review features four articles on payment
      and service delivery for care of individuals with human immunodeficiency virus
      (HIV) or acquired immunodeficiency syndrome (AIDS). These articles focus on the
      following topics: the cost and financing of care for persons with HIV disease,
      Medicare utilization of beneficiaries with AIDS, HIV/AIDS drug assistance
      programs funded under Title II of the Ryan White Care Act, and health-based
      payment systems for HIV/AIDS.

PMID- 25372979
TI  - Untargeted profiling of tracer-derived metabolites using stable isotopic labeling
      and fast polarity-switching LC-ESI-HRMS.
AB  - An untargeted metabolomics workflow for the detection of metabolites derived from
      endogenous or exogenous tracer substances is presented. To this end, a recently
      developed stable isotope-assisted LC-HRMS-based metabolomics workflow for the
      global annotation of biological samples has been further developed and extended.
      For untargeted detection of metabolites arising from labeled tracer substances,
      isotope pattern recognition has been adjusted to account for nonlabeled moieties
      conjugated to the native and labeled tracer molecules. Furthermore, the workflow
      has been extended by (i) an optional ion intensity ratio check, (ii) the
      automated combination of positive and negative ionization mode mass spectra
      derived from fast polarity switching, and (iii) metabolic feature annotation.
      These extensions enable the automated, unbiased, and global detection of tracer
      derived metabolites in complex biological samples. The workflow is demonstrated
      with the metabolism of (13)C9-phenylalanine in wheat cell suspension cultures in
      the presence of the mycotoxin deoxynivalenol (DON). In total, 341 metabolic
      features (150 in positive and 191 in negative ionization mode) corresponding to
      139 metabolites were detected. The benefit of fast polarity switching was
      evident, with 32 and 58 of these metabolites having exclusively been detected in
      the positive and negative modes, respectively. Moreover, for 19 of the remaining
      49 phenylalanine-derived metabolites, the assignment of ion species and, thus,
      molecular weight was possible only by the use of complementary features of the
      two ion polarity modes. Statistical evaluation showed that treatment with DON
      increased or decreased the abundances of many detected metabolites. 

PMID- 25372980
TI  - Blood flow vortices along the main pulmonary artery measured with MR imaging for
      diagnosis of pulmonary hypertension.
AB  - PURPOSE: To approximate the functional relationship between invasively measured
      mean pulmonary arterial pressure (mPAP) and the phase-contrast magnetic resonance
      (MR) imaging-derived duration of vortical blood flow along the main pulmonary
      artery and to analyze its applicability for noninvasive diagnosis of pulmonary
      hypertension (PH) and borderline mPAP. MATERIALS AND METHODS: The local ethics
      review board approved this prospective study of 145 patients suspected of having
      PH (69 patients with PH, 19 patients with borderline mPAP, and 57 patients with
      normal mPAP) who underwent right heart catheterization (RHC) and three
      directional phase-contrast MR imaging of the main pulmonary artery. Velocity
      fields were viewed with dedicated software and evaluated for the duration of
      vortical blood flow in the main pulmonary artery (tvortex, the percentage of
      cardiac phases with vortex present). The relationship between mPAP at RHC and
      tvortex was assessed by means of a segmented linear regression model, and by
      Bland-Altman and receiver operating characteristic curve analyses. RESULTS: The
      relationship between mPAP and tvortex was described adequately (R(2) = 0.95) as
      linearly increasing, from tvortex of 0% (mPAP <= 16.0 mm Hg) with a slope of
      1.59% per millimeter of mercury. The standard deviation between mPAP values
      derived from RHC and those estimated by using tvortex was 3.9 mm Hg. The area
      under the curve for tvortex-based diagnosis of PH was 0.994 (95% confidence
      interval [CI]: 0.982, 0.998), and the calculated PH cut-off value (tvortex >=
      14.3%) resulted in sensitivity of 0.97 (95% CI: 0.90, 0.99) and specificity of
      0.96 (95% CI: 0.89, 0.99). Vortical blood flow with tvortex less than 14.3% was
      specific for borderline mPAP. CONCLUSION: Duration of vortical blood flow in the
      main pulmonary artery that is determined by using phase-contrast MR imaging
      allows accurate estimation of elevated mPAP and diagnosis of PH. Clinical trial
      registration no. NCT00575692.

PMID- 25372984
TI  - A twisted-intramolecular-charge-transfer (TICT) based ratiometric fluorescent
      thermometer with a mega-Stokes shift and a positive temperature coefficient.
AB  - The fluorescence intensity of N,N-dimethyl-4-((2-methylquinolin-6
      yl)ethynyl)aniline exhibits an unusual intensification with increasing
      temperature, by activating more vibrational bands and leading to stronger TICT
      emissions upon heating in dimethyl sulfoxide. Based on the different temperature
      dependence at various wavelengths, as shown in the TICT fluorescence spectrum,
      this dye can be employed to ratiometrically detect temperature. 

PMID- 25372985
TI  - High electrochemical selectivity of edge versus terrace sites in two-dimensional
      layered MoS2 materials.
AB  - Exploring the chemical reactivity of different atomic sites on crystal surface
      and controlling their exposures are important for catalysis and renewable energy
      storage. Here, we use two-dimensional layered molybdenum disulfide (MoS2) to
      demonstrate the electrochemical selectivity of edge versus terrace sites for Li-S
      batteries and hydrogen evolution reaction (HER). Lithium sulfide (Li2S)
      nanoparticles decorates along the edges of the MoS2 nanosheet versus terrace,
      confirming the strong binding energies between Li2S and the edge sites and
      guiding the improved electrode design for Li-S batteries. We also provided clear
      comparison of HER activity between edge and terrace sites of MoS2 beyond the
      previous theoretical prediction and experimental proof. 

PMID- 25372986
TI  - Multiresponsive hydrogel coassembled from phenylalanine and azobenzene
      derivatives as 3D scaffolds for photoguiding cell adhesion and release.
AB  - A multiresponsive hydrogel system coassembled from phenylalanine derivative
      gelator (LPF2) and azobenzene (Azo) derivative (PPI) is constructed, which can
      respond to temperature, pH, host-guest interaction, and photoirradiation. A set
      of techniques including circular dichroism, Fourier transform infrared
      spectroscopy, (1)H NMR, and X-ray powder diffraction confirm that the hydrogel is
      formed through hydrogen bonds between amide moieties/pyridine and carbonyl
      groups, enduing the coassembled hydrogel with multiresponsive properties that
      make it possible to control cell encapsulation and release in three-dimensional
      environments under multistimulus, for example, UV irradiation. This study brings
      a novel approach to develop multistimuli-responsive hydrogels by coassembly of
      various responsive components for biomedical interest, for example, the
      controlled delivery of various therapeutic biological agents. 

PMID- 25372987
TI  - An insight to the conserved water mediated dynamics of catalytic His88 and its
      recognition to thyroxin and RBP binding residues in human transthyretin.
AB  - Human transthyretin (hTTR) is a multifunctional protein involved in several
      amyloidogenic diseases. Besides transportation of thyroxin and vitamin-A, its
      role towards the catalysis of apolipoprotein-A1 and Abeta-peptide are also
      drawing interest. The role of water molecules in the catalytic mechanism is still
      unknown. Extensive analyses of 14 high-resolution X-ray structures of human
      transthyretin and MD simulation studies have revealed the presence of eight
      conserved hydrophilic centres near its catalytic zone which may be indispensable
      for the function, dynamics and stability of the protein. Three water molecules
      (W1, W2 and W3) form a cluster and play an important role in the recognition of
      the catalytic and RBP-binding residues. They also induce the reorganisation of
      the His88 for coupling with other catalytic residues (His90, Glu92). Another
      water molecule (W5) participate in inter-monomer recognition between the
      catalytic and thyroxin binding sites. The rest four water molecules (W6, W*, W(#)
      and W(?)) form a distorted tetrahedral cluster and impart stability to the
      catalytic core of hTTR. The conserved water mediated recognition dynamics of the
      different functional sites may provide some rational clues towards the
      understanding of the activity and mechanism of hTTR. 

PMID- 25372988
TI  - Relationship of Sensory Modality to Retention of Episodic Memory.
AB  - This study investigated the difference between episodic memory for verbal
      information presented in an oral format versus equivalent material presented in a
      written format. The study utilized the Logical Memory subtest of the Wechsler
      Memory Scales-Fourth Edition and the recently validated Morris Revision-IV
      Paragraphs. In a sample of 97 normal participants, auditory and visual memory
      performances were found to be significantly correlated (r = .651, p < .001). Post
      hoc analysis revealed a slight though not clinically significant preference for
      retention in the visual modality. The results demonstrate a high-degree
      correlation for retention of episodic memory for these two sensory modalities in
      normal participants.

PMID- 25372989
TI  - Managed care: Practice, pitfalls, and potential.
AB  - The results of coordinating and changing patterns of health care using managed
      care activities and organizations are reviewed in this article. Although
      utilization review and high-cost case management programs reduce the use of
      expensive services, incentives for providers of care, placing them at risk, are
      important for managing the intensity of health care. Managed care appears capable
      of reducing health care costs substantially. However, this increased efficiency
      has not translated to lower insurance premiums or modulated total health care
      expenditures because either purchasers are not aware or are not concerned about
      securing care at the least cost. To correct these deficiencies and deliver the
      potential of managed care, the author suggests the need to separate insurance
      into its three components parts (financing, risk spreading, and program
      management) and developed policies for each.

PMID- 25372990
TI  - Age Estimates in the National Health Accounts.
AB  - This article presents historical trends of health spending by age. Personal
      health care is broken out into seven age groups for 1987, 1996, and 1999.
      Analysis of trends in health care spending is provided separately for children
      (age 0-18), working-age adults (age 19-64), and the elderly (age 65 or over).
      Future impacts of aging are also discussed, including using the historical
      estimates in a simulation to show only the effect of changing the age mix of the
      population over the next 50 years.

PMID- 25372991
TI  - Synthesis and antiviral evaluation of novel 4'-trifluoromethylated 5'
      deoxyapiosyl nucleoside phosphonic acids.
AB  - On the basis of the discovery that the threosyl nucleoside phosphonate PMDTA is a
      potent anti-HIV compound, we synthesized several 4'-trifluoromethyl-5'
      deoxyapiosyl nucleoside phosphonic acids and evaluated their anti-HIV activity.
      An efficient synthetic route was optimized, starting from an alpha
      trifluoromethyl-alpha,beta-unsaturated ester. Glycosylation of the purine
      nucleosidic bases with a glycosyl donor yielded modified nucleoside
      intermediates, which were then phosphonated and hydrolyzed to provide the
      targeted nucleoside analogs. Once synthesized, the anti-HIV and cytotoxic
      activities of each analog were evaluated. None of the analogs showed significant
      anti-HIV activity at concentrations up to 100 MUM. 

PMID- 25372992
TI  - Short and straightforward synthesis of triphosphates of artificial nucleobase
      pairs displaying unconventional pairing scheme.
AB  - Concise, facile and efficient synthesis of 5'-O-triphosphates of 6-amino-5-nitro
      3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone (dZ) and its Watson-Crick
      complement 2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2a]-1,3,5
      triazin-4(8H)-one (dP) is reported using a one-pot synthetic procedure. 

PMID- 25372993
TI  - Design and synthesis of new acid cleavable linkers for DNA sequencing by
      synthesis.
AB  - A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and
      then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)
      TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2'
      deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator
      for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by 1H
      NMR, 31P-NMR, and HRMS with purity of up to 99%. The synthesized dye-labeled
      terminator incorporated into DNA strand successfully, and the fluorophore was
      cleaved completely under acidic conditions. The preliminary results encourage us
      to explore more acid-sensitive linkers for DNA SBS to increase the cleavage
      efficiency under weakly acidic conditions.

PMID- 25372995
TI  - Achieving cost control in the hospital outpatient department.
AB  - The rapid growth in outpatient expenditures and the congressional mandate for
      development of a prospective payment system (PPS) for these expenditures are
      discussed. Extension of diagnosis-related groups to outpatient care is shown to
      be infeasible. Alternative patient classification schemes and options for
      defining the unit of payment and establishing weights and rates are discussed. A
      PPS primarily controls price and can only address volume by defining a broad unit
      of payment, such as an episode of care. Therefore, adoption of a volume
      performance standard approach could be effective. Outpatient payment policies
      must be integrated with those of other ambulatory care providers.

PMID- 25372994
TI  - Iodine monochloride facilitated deglycosylation, anomerization, and isomerization
      of 3-substituted thymidine analogues.
AB  - The reaction of thymidine, 3-mono-, and 3,3',5'-trialkylsubstitued thymidine
      analogues with iodine monochloride (ICl) was investigated. Treatment with ICl
      resulted in rapid deglycosylation, anomerization, and isomerization of thymidine
      and 3-substituted thymidine analogues under various reaction conditions leading
      to the formation of the nucleobases as the major products accompanied by minor
      formation of alpha-furanosidic-, alpha-pyranosidic-, and beta-pyranosidic
      nucleosides. On the other hand, 3,3',5'-trisubstitued thymidine analogues were
      only deglycosylated and anomerized. These results are similar to those observed
      for the acidic hydrolysis of the glycoside bond in nucleosides, but were
      presumably caused by the Lewis acid character of an iodine electrophile. 

PMID- 25372996
TI  - Generating electric current based on the solvent-dependent charging effects of
      defective boron nitride nanosheets.
AB  - This work presents a method of generating electric current based on the defects
      of few-layer boron nitride nanosheets (BNNSs). The density functional theory
      calculations showed that the atomic charge of the B atom in acetone was more
      positive than in water. The electrostatic force microscopy measurements
      illustrated that the local electrical potential was 0.35 mV in acetone, while the
      potential signal was very difficult to capture when using water as the
      dispersant. This effect was further demonstrated by the performance of the
      acoustic energy-harvesting nanogenerator: the BNNSs were assembled into a film
      after being dispersed in acetone and then integrated into the generator device,
      generating average output current of ~0.98 nA, which was much better than 0.2 nA,
      the average output current of another device with water as the dispersant. These
      results demonstrated that solvent effects made the as-prepared BNNSs carry net
      charges, which could be utilized to harvest acoustic energy and generate current.

PMID- 25372997
TI  - Combinatorial high-throughput optical screening of high performance Pd alloy
      cathode for hybrid Li-air battery.
AB  - Combinatorial high-throughput optical screening method was developed to find the
      optimum composition of highly active Pd-based catalysts at the cathode of the
      hybrid Li-air battery. Pd alone, which is one-third the cost of Pt, has
      difficulty in replacing Pt; therefore, the integration of other metals was
      investigated to improve its performance toward oxygen reduction reaction (ORR).
      Among the binary Pd-based catalysts, the composition of Pd-Ir derived catalysts
      had higher performance toward ORR compared to other Pd-based binary combinations.
      The composition at 88:12 at. % (Pd: Ir) showed the highest activity toward ORR at
      the cathode of the hybrid Li-air battery. The prepared Pd(88)Ir(12)/C catalyst
      showed a current density of -2.58 mA cm(-2) at 0.8 V (vs RHE), which was around
      30% higher compared to that of Pd/C (-1.97 mA cm(-2)). When the prepared
      Pd(88)Ir(12)/C catalyst was applied to the hybrid Li-air battery, the
      polarization of the cell was reduced and the energy efficiency of the cell was
      about 30% higher than that of the cell with Pd/C.

PMID- 25372998
TI  - Dissociation of diglycolamide complexes of Ln3+ (Ln = La-Lu) and An3+ (An = Pu,
      Am, Cm): redox chemistry of 4f and 5f elements in the gas phase parallels
      solution behavior.
AB  - Tripositive lanthanide and actinide ions, Ln(3+) (Ln = La-Lu) and An(3+) (An =
      Pu, Am, Cm), were transferred from solution to gas by electrospray ionization as
      Ln(L)3(3+) and An(L)3(3+) complexes, where L = tetramethyl-3-oxa-glutaramide
      (TMOGA). The fragmentation chemistry of the complexes was examined by collision
      induced and electron transfer dissociation (CID and ETD). Protonated TMOGA,
      HL(+), and Ln(L)(L-H)(2+) are the major products upon CID of La(L)3(3+),
      Ce(L)3(3+), and Pr(L)3(3+), while Ln(L)2(3+) is increasingly pronounced beyond
      Pr. A C-Oether bond cleavage product appears upon CID of all Ln(L)3(3+); only for
      Eu(L)3(3+) is the divalent complex, Eu(L)2(2+), dominant. The CID patterns of
      Pu(L)3(3+), Am(L)3(3+), and Cm(L)3(3+) are similar to those of the Ln(L)3(3+) for
      the late Ln. A striking exception is the appearance of Pu(IV) products upon CID
      of Pu(L)3(3+), in accord with the relatively low Pu(IV)/Pu(III) reduction
      potential in solution. Minor divalent Ln(L)2(2+) and An(L)2(2+) were produced for
      all Ln and An; with the exception of Eu(L)2(2+) these complexes form adducts with
      O2, presumably producing superoxides in which the trivalent oxidation state is
      recovered. ETD of Ln(L)3(3+) and An(L)3(3+) reveals behavior which parallels that
      of the Ln(3+) and An(3+) ions in solution. A C-Oether bond cleavage product, in
      which the trivalent oxidation state is preserved, appeared for all complexes;
      charge reduction products, Ln(L)2(2+) and Ln(L)3(2+), appear only for Sm, Eu, and
      Yb, which have stable divalent oxidation states. Both CID and ETD reveal
      chemistry that reflects the condensed-phase redox behavior of the 4f and 5f
      elements. 

PMID- 25372999
TI  - Confidence Interval Estimation for Sensitivity to the Early Diseased Stage Based
      on Empirical Likelihood.
AB  - Many disease processes can be divided into three stages: the non-diseased stage:
      the early diseased stage, and the fully diseased stage. To assess the accuracy of
      diagnostic tests for such diseases, various summary indexes have been proposed,
      such as volume under the surface (VUS), partial volume under the surface (PVUS),
      and the sensitivity to the early diseased stage given specificity and the
      sensitivity to the fully diseased stage (P2). This paper focuses on confidence
      interval estimation for P2 based on empirical likelihood. Simulation studies are
      carried out to assess the performance of the new methods compared to the existing
      parametric and nonparametric ones. A real dataset from Alzheimer's Disease
      Neuroimaging Initiative (ADNI) is analyzed. 

PMID- 25373000
TI  - Improving brush polymer infrared one-dimensional photonic crystals via linear
      polymer additives.
AB  - Brush block copolymers (BBCPs) enable the rapid fabrication of self-assembled one
      dimensional photonic crystals with photonic band gaps that are tunable in the UV
      vis-IR, where the peak wavelength of reflection scales with the molecular weight
      of the BBCPs. Due to the difficulty in synthesizing very large BBCPs, the
      fidelity of the assembled lamellar nanostructures drastically erodes as the
      domains become large enough to reflect IR light, severely limiting their
      performance as optical filters. To overcome this challenge, short linear
      homopolymers are used to swell the arrays to ~180% of the initial domain spacing,
      allowing for photonic band gaps up to ~1410 nm without significant opacity in the
      visible, demonstrating improved ordering of the arrays. Additionally, blending
      BBCPs with random copolymers enables functional groups to be incorporated into
      the BBCP array without attaching them directly to the BBCPs. The addition of
      short linear polymers to the BBCP arrays thus offers a facile means of improving
      the self-assembly and optical properties of these materials, as well as adding a
      route to achieving films with greater functionality and tailorability, without
      the need to develop or optimize the processing conditions for each new brush
      polymer synthesized. 

PMID- 25373003
TI  - Nursing leadership in skilled nursing: a journey to clinical excellence.

PMID- 25373006
TI  - Updated and expanded: AGS' geriatric nursing review syllabus.

PMID- 25373008
TI  - A pressure-driven capillary electrophoretic system with injection valve sampling.
AB  - To improve repeatability and efficiency and to simplify the operation procedure
      of capillary electrophoresis (CE), a pressurized CE system (p-CE) with injection
      valve sampling was developed. It consisted of one high-pressure pump, a six-port
      injection valve, a PEEK cross, a separation and back pressure capillary, an
      ultraviolet-visible detector and a high voltage power supply. The pressure-driven
      flow ranging from 4.5 nL min(-1) to 0.81 MUL min(-1) in the separation capillary
      was produced by splitting to the flow from the high-pressure pumps (0.005-0.4 mL
      min(-1)). Nano-volume sample injection (<10 nL) was conducted by a micro-volume
      rotary injector (0.5-5 MUL) with flow splitting. In the p-CE system, the new
      commercial capillary could be directly used without any wash, and the capillary
      flush process between runs was also eliminated. In this case, the analytes were
      driven toward the outlet of the separation capillary by the pressurized flow, the
      electric field force and minute electroosmotic flow, and they were separated
      owing to the electrophoretic mobility. The p-CE system allows for the independent
      variation of the pressurized flow rate and electrical field and electrophoretic
      separation of good repeatability (below 3%) under high electrical fields (500
      1000 V cm(-1)) and flow rate gradient modes. The feasibility of the p-CE system
      in real analysis was demonstrated by iodate quantification in iodized table
      salts. The separation of iodide and iodate was realized within 0.3 min, proving
      its high analytical speed. 

PMID- 25373009
TI  - Fermi resonance effects in the vibrational spectroscopy of methyl and methoxy
      groups.
AB  - A theoretical model Hamiltonian [J. Chem. Phys. 2013, 138, 064308] for describing
      vibrational spectra associated with the CH stretch of CH2 groups is extended to
      molecules containing methyl and methoxy groups. Results are compared to the
      infrared (IR) spectroscopy of four molecules studied under supersonic expansion
      cooling in gas phase conditions. The molecules include 1,1-diphenylethane (DPE),
      1,1-diphenylpropane (DPP), 2-methoxyphenol (guaiacol), and 1,3-dimethoxy-2
      hydroxybenzene (syringol). Transforming the bending normal mode vibrations of CH3
      groups to local scissor vibrations leads to model Hamiltonians which share many
      features present in our model Hamiltonian for the stretching vibrations of CH2
      Fermi coupled to scissor modes. The central difference arises from the greater
      scissor-scissor coupling present in the CH3 case. Comparing anharmonic couplings
      between these modes and the stretch-bend Fermi coupling for a variety of systems,
      it is observed that the anharmonic couplings are robust; their values are similar
      for the four molecules studied as well as for ethane and methanol. Similar
      results are obtained with both density functional theory and coupled-cluster
      calculations. This robustness suggests a new parametrization of the model
      Hamiltonian that reduces the number of fitting parameters. In contrast, the
      harmonic contributions to the Hamiltonian vary substantially between the
      molecules leading to important changes in the spectra. The resulting Hamiltonian
      predicts most of the major spectral features considered in this study and
      provides insights into mode mixing and the consequences of the mixing on
      dynamical processes that follow ultrafast CH stretch excitation. 

PMID- 25373010
TI  - Master and slave relationship between two types of self-propagating insulin
      amyloid fibrils.
AB  - Cross-seeding of fibrils of bovine insulin (BI) and Lys(B31)-Arg(B32) human
      insulin analog (KR) induces self-propagating amyloid variants with infrared
      features inherited from mother seeds. Here we report that when native insulin (BI
      or KR) is simultaneously seeded with mixture of equal amounts of both templates
      (i.e., of separately grown fibrils of BI and KR), the phenotype of resulting
      daughter fibrils is as in the case of the purely homologous seeding: heterologous
      cotemplates accelerate the fibrillation but do not determine infrared traits of
      the daughter amyloid. This implies that fibrillation-promoting and structure
      imprinting properties of heterologous seeds become uncoupled in the presence of
      homologous seeds. We argue that explanation of such behavior requires that
      insulin molecules partly transformed through interactions with heterologous
      fibrils are subsequently recruited by homologous seeds. The selection bias toward
      homologous daughter amyloid is exceptional: more than 200-fold excess of
      heterologous seed is required to imprint its structural phenotype upon mixed
      seeding. Our study captures a snapshot of elusive docking interactions in statu
      nascendi of elongation of amyloid fibril and suggests that different types of
      seeds may collaborate in sequential processing of soluble protein into fibrils. 

PMID- 25373011
TI  - Use of contraception by women with induced abortion in Italy.
AB  - AIM: Aim of the present study was to investigate type of contraception, if any,
      used by women with induced abortion. METHODS: Retrospective analysis on the
      medical records of 1782 women with induced abortion performed at the University
      Hospital of Modena (Italy) between 2009 and 2011. RESULTS: Some kind of
      contraception was used by 81.1% of women with induced abortion. At time of
      conception most of these women (39%) had used withdrawal, 19% natural methods,
      15.2% condom, 7% hormonal contraception (95% estrogen plus progestin for any
      route) and 0.4% copper-IUD. None was using implants or levonorgestrel-IUD.
      Figures of past use of hormonal contraception were much higher than those present
      at the time of the unwanted pregnancy (50.3% vs. 7%; P<0.0001). A higher
      prevalence of condom use (19.7% vs. 10.9%; P<0.0001), and a lower prevalence of
      natural methods (14.5% vs. 21.6%; P<0.001) were found in single vs. married
      women. Use of no contraception was more prevalent among low vs. highly educated
      women with induced abortion (22.2% vs. 14.2%; P<0.02), but was not related to
      marital status. Prevalence of use of the different contraceptives is different
      from the one described in the general population, suggesting differences in
      contraceptive efficacy among the different methods. CONCLUSION: Women with
      induced abortion infrequently use long term or hormonal contraception. In half of
      the cases the latter has been used at least once in life, but then it has been
      abandoned. Appropriate education and contraceptive counselling, personalization
      and follow-up may reduce induced abortion.

PMID- 25373012
TI  - [Combination inositol and glucomannan in PCOS patients].
AB  - AIM: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies
      of the reproductive age in women. PCOS is an endocrine-metabolic disorder
      characterized by insulin resistance. Aim of the study was to evaluate the
      efficacy of natural substances such as inositol and glucomannan, and their
      combination in reducing glucose levels and improving insulin sensitivity in PCOS
      patients. METHODS: Forty women with clinical and endocrinological signs of PCOS
      were enrolled in the study and divided into three groups, including ten women
      each. The three groups were respectively treated with the combination inositol
      and glucomannan (A group), inositol (B group), glucomannan (C group) for a period
      of 3 months. Plasma levels of glucose and insulin were evaluated before and after
      treatment in our laboratory. RESULTS: There was a reduction in blood glucose and
      insulin levels, with particular significance in the group treated with the
      combination of inositol-glucomannan. CONCLUSION: Present results show that the
      association-inositol glucomannan may represent a good therapeutic strategy in the
      treatment of PCOS women with insulin resistance.

PMID- 25373013
TI  - Higher levels of circulating chemerin in both lean and obese patients with
      polycystic ovary syndrome.
AB  - AIM: The aim of this paper was to compare serum chemerin levels in nonobese and
      overweight/obese patients with polycystic ovary syndrome (PCOS) with lean
      controls. METHODS: Seventy women with newly diagnosed or untreated PCOS and 38
      age-matched nonobese healthy controls were enrolled in the present study.
      Participants with PCOS were categorized as nonobese (Body Mass Index [BMI] <25
      kg/m2, N.=36) or overweight/obese (BMI 25-29.9 kg/m2 and >=30 kg/m2,
      respectively, N.=34). Anthropometric, metabolic and hormonal patterns, and serum
      chemerin were measured. RESULTS: Serum chemerin tended to be higher in obese PCOS
      group than in nonobese PCOS women but did not reach statistical significance.
      Nonobese healthy controls had significantly lower chemerin levels than two PCOS
      groups (P<0.001). Fasting insulin (P<0.05) and homeostasis model assessment index
      (P<0.05) were significantly higher in obese women with PCOS than in other two
      groups. Also, these two parameters were higher in lean patients with PCOS than in
      healthy controls (P<0.05). In multiple linear regression analyses, chemerin was
      significantly associated with BMI (beta-coefficient =0.336, P<0.01), and
      triglyceride (beta-coefficient =0.298, P<0.05). CONCLUSION: Chemerin levels were
      significantly increased not only in obese PCOS women but also in nonobese PCOS
      women. The physiological significance of elevated serum chemerin in PCOS remains
      unclear.

PMID- 25373014
TI  - A pharmacogenetic-driven approach for controlled ovarian hyperstimulation by FSH
      treatment.
AB  - AIM: The aim of this study was to develop a pharmacogenetic- (PGx) driven
      approach for a controlled ovarian hyperstimulation (COH) treatment protocol used
      for in vitro fertilization procedures. The enrolled patients were genotyped for a
      single nucleotide polymorphism (SNP) N680S, within the FSHR. METHODS: Seventy
      eight women, who had previously received at least two COH cycles without positive
      fertilization with FSH and AMH values <10 mUI/mL and >0.3 ng/mL respectively were
      enrolled. They were genotyped for N680S and then categorized in high (HR),
      intermediate (IR), and poor responders (PR). Each subgroup received a tailored
      FSH treatment of 100, 225, and 400 UI/mL, respectively. The response was
      evaluated considering differences with previous COH cycle in terms of number of
      follicles (FR), oocytes (OR), and embryos produced (EMB). RESULTS: With regards
      to the endpoint considered comparing the non-PGx with the PGx approach, for what
      regards the FR a statistically significant increase of their numbers was observed
      with the PGx-tailored approach (HR P<0.0001; IR P=0.00892; PR P=0.0032). Similar
      statistical significant results were also achieved for OR but only for HR
      (P<0.0001) and IR (P=0.00169). Last but not least for the EMB (HR P<0.001; IR
      P=0.00670 and PR P<0.0001) all the different genotype considered achieved a
      statistical significance. CONCLUSION: This study, although with a limited number
      of enrolled patients, showed that a FSH treatment with a PGx-driven approach
      might have the potential to improve COH clinical outcome.

PMID- 25373015
TI  - Fertility before and after surgery for deep infiltrating endometriosis with and
      without bowel involvement: a literature review.
AB  - AIM: Endometriosis affects from 10% to 15% of women of childbearing age and 20%
      of these women have deep infiltrating endometriosis (DIE). The goal of this
      review was to assess the impact of various locations of DIE on spontaneous
      fertility and the benefit of surgery and Medically Assisted Reproduction (MAR)
      (in vitro fertilization and intrauterine insemination) on fertility outcomes.
      METHODS: MEDLINE search for articles on fertility in women with DIE published
      between 1990 and April 2013 using the following terms: "deep infiltrative
      endometriosis", "colorectal", "bowel", "rectovaginal", "uterosacral", "vaginal",
      "bladder" and "fertility" or "infertility". Twenty-nine articles reporting
      fertility outcomes in 2730 women with DIE were analysed. RESULTS: Among the women
      with DIE and no bowel involvement (N.=1295), no preoperative data on spontaneous
      pregnancy rate (PR) were available. The postoperative spontaneous PR rate in
      these women was 50.5% (95% Confidence Interval [CI] =46.8-54.1) and overall PR
      (spontaneous pregnancies and after MAR) was 68.3% (95% CI=64.9-71.7). No
      evaluation of fertility outcome according to locations of DIE was feasible. For
      women with DIE with bowel involvement without surgical management (N.=115), PR
      after MAR was 29%; 95% CI=20.7-37.4). For those with bowel involvement who were
      surgically managed (N.=1320), postoperative spontaneous PR was 28.6% (95% CI=25
      32.3) and overall postoperative PR was 46.9% (95% CI=42.9-50.9). CONCLUSION: For
      women with DIE without bowel involvement, surgery alone offers a high spontaneous
      PR. For those with bowel involvement, the low spontaneous and relatively high
      overall PR suggests the potential benefit of combining surgery and MAR.

PMID- 25373016
TI  - Cellular and biochemical mechanisms, risk factors and management of preterm
      birth: state of the art.
AB  - Preterm birth (PTB) is usually defined as a delivery before 37 completed weeks or
      259 days of gestation. World Health Organization estimates a worldwide incidence
      of PTB of 9.6%. Infants born preterm are at higher risks than infants born at
      term for mortality, and acute and chronic morbidity. Major causes of PTB are the
      following: spontaneous preterm labor with intact membranes (50%), labor induction
      or caesarean delivery for maternal or fetal indications (30%), and preterm
      premature rupture of membranes or PPROM (20%). The aim of this review is to
      analyze this medical condition, focusing on cellular and biochemical mechanisms,
      maternal risk factors and role of inflammation and infections in preterm
      premature rupture of membranes (PPROM) and PTB. Moreover we will discuss about
      the proper therapeutic strategies for its management. Although different methods
      have been introduced to predict the advent of preterm labour in asymptomatic
      women, possibilities for real primary prevention are rare. An early estimation of
      potential risk factors is pivotal in the secondary prevention of PTB. Finally
      most efforts so far have been tertiary interventions. These measures have reduced
      perinatal morbidity and mortality. Advances in primary and secondary care will be
      needed to prevent prematurity-related illness in infants and children. 

PMID- 25373017
TI  - Health Care Indicators.
AB  - THIS REGULAR FEATURE OF THE JOURNAL INCLUDES A DISCUSSION OF EACH OF THE
      FOLLOWING FOUR TOPICS: community hospital statistics; employment, hours, and
      earnings in the private health sector; health care prices; and national economic
      indicators. These statistics are valuable in their own right for understanding
      the relationship between the health care sector and the overall economy. In
      addition, they allow us to anticipate the direction and magnitude of health care
      cost changes prior to the availability of more comprehensive data.

PMID- 25373018
TI  - Electrode materials, thermal annealing sequences, and lateral/vertical phase
      separation of polymer solar cells from multiscale molecular simulations.
AB  - The nanomorphologies of the bulk heterojunction (BHJ) layer of polymer solar
      cells are extremely sensitive to the electrode materials and thermal annealing
      conditions. In this work, the correlations of electrode materials, thermal
      annealing sequences, and resultant BHJ nanomorphological details of P3HT:PCBM BHJ
      polymer solar cell are studied by a series of large-scale, coarse-grained (CG)
      molecular simulations of system comprised of PEDOT:PSS/P3HT:PCBM/Al layers.
      Simulations are performed for various configurations of electrode materials as
      well as processing temperature. The complex CG molecular data are characterized
      using a novel extension of our graph-based framework to quantify morphology and
      establish a link between morphology and processing conditions. Our analysis
      indicates that vertical phase segregation of P3HT:PCBM blend strongly depends on
      the electrode material and thermal annealing schedule. A thin P3HT-rich film is
      formed on the top, regardless of bottom electrode material, when the BHJ layer is
      exposed to the free surface during thermal annealing. In addition, preferential
      segregation of P3HT chains and PCBM molecules toward PEDOT:PSS and Al electrodes,
      respectively, is observed. Detailed morphology analysis indicated that,
      surprisingly, vertical phase segregation does not affect the connectivity of
      donor/acceptor domains with respective electrodes. However, the formation of
      P3HT/PCBM depletion zones next to the P3HT/PCBM-rich zones can be a potential
      bottleneck for electron/hole transport due to increase in transport pathway
      length. Analysis in terms of fraction of intra- and interchain charge transports
      revealed that processing schedule affects the average vertical orientation of
      polymer chains, which may be crucial for enhanced charge transport, nongeminate
      recombination, and charge collection. The present study establishes a more
      detailed link between processing and morphology by combining multiscale molecular
      simulation framework with an extensive morphology feature analysis, providing a
      quantitative means for process optimization.

PMID- 25373019
TI  - Pyelonephritis (acute) in non-pregnant women.
AB  - INTRODUCTION: Pyelonephritis is usually caused by ascent of bacteria (most often
      Escherichia coli) from the bladder, and is more likely in people with structural
      or functional urinary tract abnormalities. The prognosis is good if
      pyelonephritis is treated appropriately, but complications include renal abscess,
      renal impairment, and septic shock. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical question: What are
      the effects of antibiotic treatments for acute pyelonephritis in non-pregnant
      women with uncomplicated infection? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to November 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
      four studies that met our inclusion criteria. CONCLUSIONS: In this systematic
      review we present information relating to the effectiveness and safety of the
      following interventions: antibiotics (intravenous), antibiotics (oral), and
      antibiotics (switch therapy).

PMID- 25373021
TI  - What is biocompatibility?: a new definition based on the latest technology.
AB  - Biomaterials have been evolving for a number of decades, and it is about time
      that better categorizations of biocompatibility were devised to describe them. At
      least that is the view of Buddy Ratner, professor of bioengineering and chemical
      engineering, and Michael L. and Myrna Darland Endowed Chair in Technology
      Commercialization at the University of Washington, as well as director of
      University of Washington Engineered Biomaterials (UWEB), the university's
      engineered biomaterials program. 

PMID- 25373022
TI  - Biocompatible medical devices: raise the bar for health care.
AB  - From pacemakers to hip replacements, sophisticated sensors to catheters, medical
      devices are helping millions of patients live far better and even much longer
      lives. The possibilities are nearly endless, provided the new devices are
      biocompatible. In other words, they must not have harmful consequences for the
      patient, but they must also play some role and function well within the immensely
      complicated and not completely understood human body. 

PMID- 25373023
TI  - Multifaceted biomaterials extend to multiple uses: new developments in
      biocompatibility.
AB  - In research laboratories around the world, scientists and engineers are taking
      newly reported insights about how the human body works, contributing new insights
      themselves, and then combining that new knowledge with innovative approaches to
      materials development. The result is a collection of biomaterials that promise to
      make a vast range of medical devices biocompatible and to increase the level of
      biocompatibility of those devices that are already considered biocompatible. 

PMID- 25373024
TI  - The cortical mouse: a piece of forgotten history in noninvasive
      brain&#8211;computer interfaces.
AB  - Early research on brain-computer interfaces (BCIs) was fueled by the study of
      event-related potentials (ERPs) by Farwell and Donchin, who are rightly credited
      for laying important groundwork for the BCI field. However, many other
      researchers have made substantial contributions that have escaped the radar
      screen of the current BCI community. For example, in the late 1980s, I worked
      with a brilliant multidisciplinary research group in electrical engineering at
      the University of Florida, Gainesville, headed by Dr. Donald Childers. Childers
      should be well known to long-time members of the IEEE Engineering in Medicine and
      Biology Society since he was the editor-in-chief of IEEE Transactions on
      Biomedical Engineering in the 1970s and the recipient of one of the most
      prestigious society awards, the William J. Morlock Award, in 1973. 

PMID- 25373025
TI  - Considering endoscopic design: a snakebot prototype.
AB  - Endoscope design is at the intersection of many disciplines, including robot
      design, computer science, material science, and medical devices. When considering
      design features, it is important to ensure that the device safely navigates the
      patient's body and, once in position, performs the task required by the surgeon.
      Whether surgical access is achieved through existing orifices or by small
      incisions, the goal is to provide the surgeon with a stable platform within the
      patient from which to cut, suture, and grasp, while transmitting a clear image.
      The device described in this article can generate force at the tip of the
      snakebot in any direction without pressing against interstitial tissue to
      redirect the applied force. 

PMID- 25373026
TI  - Cardiac risk assessment: when and who? [Retrospectroscope].
AB  - Think about the above lines taken from the Old Testament: At 130 years of age,
      Adam begat a son and at 800 he kept going, quitting this earthly life at 930.
      These numbers surpass by far the limits our current experience teaches us,
      however, perhaps a life span into the hundreds of years is ? What if, in the
      future, science were to do away with disease? What then would cause people to
      die: accidents, killings, wars? How old would old age be? Aging has always been a
      hot topic for research (with considerable quackery, too). For example, animals
      with a slow metabolism tend to live longer than those with a fast metabolism.
      Compare the average life span of a mouse with that of a turtle. Apparently,
      meditators are able to slow their metabolism down [1]. 

PMID- 25373027
TI  - Diabetes screening in the workplace.
AB  - The prevalence of diabetes has increased worldwide and the pathophysiological
      problems associated with diabetes increase the potential for employees' physical
      disabilities. These complications, including neuropathy, nephropathy, and visual
      impairment, negatively impact the job performance of employees and compromise
      workplace safety. Occupational health nurses can provide diabetes screening
      programs to employees and identify chronic disease risk factors early. This
      article describes an occupational diabetes screening program at a major
      corporation in Belize, Central America, defines diabetes, outlines the diabetes
      teaching plan, and presents the demographics of the participants and results of
      the screening. Cultural considerations and recommendations for future
      occupational diabetes screenings are proposed.

PMID- 25373029
TI  - Ebola virus disease epidemic.
AB  - The Ebola virus disease epidemic now constitutes an international public health
      emergency. Occupational and environmental health nurses can collaborate with
      international colleagues to halt Ebola virus transmission within Africa, protect
      workers from exposures, and prevent another pandemic.

PMID- 25373030
TI  - Dermatology procedures: foreword.

PMID- 25373031
TI  - Dermatology procedures: dermatoscopy.
AB  - A dermatoscope is a handheld device with 10-fold magnification that uses
      polarized and nonpolarized light in visualizing the detailed structure of skin
      lesions. Dermatoscopy is used clinically to aid in diagnosis of skin lesions that
      cannot be identified definitively during a visual examination or to confirm
      suspected visual diagnoses. Used in this manner, dermatoscopy improves diagnostic
      accuracy and decreases the rate of unnecessary biopsies. In the widely used two
      step dermatoscopy method, the first step in evaluating a lesion is to determine
      if it is melanotic (ie, contains pigment) or nonmelanotic. If it is nonmelanotic,
      dermatoscopic examination is used to identify structural features typical of
      common nonpigmented lesions. If these features are identified, a diagnosis is
      confirmed. If they cannot be identified, a biopsy of the lesion should be
      considered. If the lesion is melanotic, the evaluation moves to Step 2. In this
      step, pattern analysis and/or other approaches are used to determine if the
      pigment in the lesion has features typical of a benign pigmented lesion or if it
      is typical of or suspicious for melanoma. In the latter instance, the lesion
      should be excised or biopsied. 

PMID- 25373032
TI  - Dermatology procedures: microdermabrasion and chemical peels.
AB  - Microdermabrasion and chemical peels are exfoliation procedures used to treat
      various cosmetic and medical skin conditions. Microdermabrasion involves
      mechanical abrasion of the skin with a handheld motorized device. Chemical peels
      involve applying acids directly to the skin. After partial destruction of the
      skin, these modalities rejuvenate the skin by stimulating production of new skin
      as well as inducing changes such as increasing production of collagen. Patients
      planning to undergo one of these procedures should be screened for absolute or
      relative contraindications, including recent use of retinoids, active skin
      infection, and immunosuppression. In addition, patients with histories of herpes
      simplex virus infection in or near the area to be treated should receive
      antiviral prophylaxis. Microdermabrasion is performed by passing a handheld
      abrasion device over the skin. Chemical peels are performed by applying liquid
      acid to the skin. After a chemical peel, patients treated with strong acids may
      require acid neutralization to protect the skin from sun exposure and reduce
      pain. Patients should receive aftercare instructions about application of topical
      agents to reduce pain, erythema, and itching. Patients undergoing chemical peels
      should be instructed specifically not to remove peeling skin but to let it shed
      spontaneously. 

PMID- 25373033
TI  - Dermatology procedures: skin biopsy.
AB  - The procedures used most often for office-based skin biopsies are two types of
      shave biopsies, punch biopsy, and elliptical biopsy performed with a scalpel.
      Tangential shave biopsy is superficial and best suited to small, raised, benign
      lesions. Saucerization shave biopsy is deeper and is used for excisional biopsy
      of atypical nevi, for squamous and basal cell carcinomas, and as initial biopsy
      for suspected melanoma. Punch biopsy also removes deeper tissue and can be used
      to excise or sample a variety of lesions, including pigmented nevi. Elliptical
      biopsy using a scalpel is reserved for larger lesions not amenable to shave or
      punch biopsies. It is not necessary to discontinue anticoagulants before office
      based skin biopsy is performed or to administer topical or systemic antibiotics.
      When sutures are used for wound closure, it is important for the sutures to have
      appropriate tensile strength. Multifilament sutures should be avoided in areas
      prone to infection, such as the feet. An important complication of skin biopsy is
      the development of hypertrophic and keloid scars, which are more common among
      patients with dark skin. Injection of triamcinolone or verapamil into a maturing
      scar can minimize the possibility of hypertrophic and keloid scars. 

PMID- 25373034
TI  - Dermatology procedures: laser management and related therapies.
AB  - Laser therapy is a new approach to treating cosmetic and medical skin conditions.
      Different laser units emit light at different wavelengths, and each wavelength
      acts on a different chromophore in tissue that is sensitive to the wavelength.
      Commonly targeted chromophores are hemoglobin (when vascular lesions are being
      treated), melanin (in pigmented lesions), and water (targeted to cause skin
      peeling that results in collagen remodeling). Ink is an exogenous chromophore
      targeted during laser treatments to remove tattoos. Lasers can be used to treat a
      variety of medical skin conditions, including psoriasis and onychomycosis. Care
      must be taken with lasers to avoid burns and inadvertent destruction of melanin
      containing tissue in darker-skinned patients. Precautions also must be taken to
      prevent exposure of the eyes to the laser. Intense-pulsed light therapy differs
      from laser therapy in that it uses multiwavelength light, making it useful for
      managing many skin conditions with a single unit. However, this same
      characteristic can result in inadvertent damage to tissue adjacent to the treated
      site. Other approaches include radiofrequency, which uses radiofrequency energy
      to heat and destroy subcutaneous tissue, and photodynamic therapy, which uses a
      light source in combination with a photosensitizing agent. 

PMID- 25373035
TI  - Preventing psychological disorders in service members and their families: an
      assessment of programs.

PMID- 25373036
TI  - Luther Terry Award.

PMID- 25373038
TI  - Melanized fungi and military medical operations in the nuclear environment.

PMID- 25373037
TI  - The next 50 years.

PMID- 25373039
TI  - Screening for sickle-cell trait at accession to the United States military.

PMID- 25373040
TI  - Returning to duty from temporary disability in the U.S. Army: observational data
      and commentary for commanders, providers, and soldiers.
AB  - Before 2011, Army commanders were unable to achieve complete visibility of
      soldiers possessing temporary medical limitations. The creation of time-limited
      definitions and technical categorization of this group, now known as the
      medically not ready (MNR) population, eventually allowed its quantification. With
      heightened visibility of the group, leaders in the Fort Stewart community
      facilitated its management through soldier medical readiness councils. In this
      commentary, we introduce a project that identified and tracked a cohort of 2,490
      MNR soldiers for a 1-year period until they either recovered or entered the
      medical separation process. We identified that musculoskeletal injuries accounted
      for a heretofore unrecognized 87.4% majority of the MNR population. Prognosis of
      the MNR population was generally good. Fifty percent of the population returned
      to duty within 90 days of illness/injury. Seventy-seven percent returned to duty
      during the follow-up period. Although low back and knee/leg injuries were the
      largest contributors to the MNR population, low back issues were more likely to
      result in medical separation. Traumatic brain injury and post-traumatic stress
      disorder did not contribute significantly to the MNR population. This article
      seeks to describe the natural history of the MNR category of temporary disability
      for commanders, providers, and soldiers alike. 

PMID- 25373041
TI  - Clinical course of alcohol use in veterans following an AUDIT-C Positive Screen.
AB  - There is little known regarding the typical trajectory of alcohol use following a
      positive screen for hazardous alcohol use. This information would help primary
      care providers as they attempt to determine the best use of patient visits that
      might include brief alcohol interventions versus other competing medical demands.
      This longitudinal observational study included 98 Veterans who screened positive
      on the Alcohol Use Disorders Identification Test-Consumption (>3) and were asked
      to report on their alcohol use every 3 months for 1 year. Using latent class
      growth modeling, we identified the best fitting latent class structure for each
      outcome of high-risk and heavy drinking, respectively. There was a class of
      participants with increased probability of having a high-risk week or episode of
      heavy drinking as well as a group of participants who appeared to maintain their
      current drinking pattern. Although the latent class growth modeling suggested
      that none of the groups of participants reduced the likelihood of occurrence of
      heavy drinking days, two groups did significantly reduce the probability of
      having a hazardous alcohol use week. These results suggest that there are
      specific classes of patients who are less likely to change their alcohol use
      following a positive screen, especially those patients who report engaging in
      heavy drinking. 

PMID- 25373042
TI  - Leveraging arthropod-borne disease surveillance assays for clinical diagnostic
      use.
AB  - Researchers at the Walter Reed Army Institute of Research have taken a joint
      service approach to filling an identified diagnostic capability gap by leveraging
      a vector surveillance assay. Specifically, the Army took a field-stable real-time
      polymerase chain reaction assay, developed by the Air Force, for dengue virus
      surveillance in arthropod vectors and collaborated with Navy researchers for
      utility in human diagnostics. As current Department of Defense diagnostic PCR
      assays employ the Joint Biological Agent Identification and Diagnostic System,
      the dengue assay was tested for use on this platform. The low rates of false
      negative and false positive dengue samples in clinical matrices demonstrate
      excellent utility as a human diagnostic assay. Overall, converting an arboviral
      vector surveillance assay to human diagnostic assay and potentially vice versa is
      both cost effective and labor reducing. Codevelopment with harmonization of
      vector surveillance and diagnostics offers monetary and resource advantages to
      the Department of Defense and should be considered as a path forward in times
      when downsizing threatens assay development and pathogen discovery. 

PMID- 25373043
TI  - Proposed objective visual system biomarkers for mild traumatic brain injury.
AB  - The challenge and search for objectively based biomarkers to assess for the
      presence of concussion/mild traumatic brain injury is a high priority for the
      military establishment. We present a documented overview of specific test areas
      and related targeted, high-yield, objectively based parameters that may be
      potential "vision biomarkers" for the detection of concussion/mild traumatic
      brain injury based on results from our laboratory and others, with emphasis on
      oculomotor aspects. These findings have military relevance with respect to the
      initial diagnosis in the battlefield and in the far-forward medical facilities,
      pre-/postdeployment issues, pre-/postvisual rehabilitation evaluation, fitness
      for-duty assessment, and establishment of a return-to-duty timeline. 

PMID- 25373044
TI  - Access, utilization, and interest in mHealth applications among veterans
      receiving outpatient care for PTSD.
AB  - Mobile health (mHealth) refers to the use of mobile technology (e.g.,
      smartphones) and software (i.e., applications) to facilitate or enhance health
      care. Several mHealth programs act as either stand-alone aids for Veterans with
      post-traumatic stress disorder (PTSD) or adjuncts to conventional psychotherapy
      approaches. Veterans enrolled in a Veterans Affairs outpatient treatment program
      for PTSD (N = 188) completed anonymous questionnaires that assessed Veterans'
      access to mHealth-capable devices and their utilization of and interest in
      mHealth programs for PTSD. The majority of respondents (n = 142, 76%) reported
      having access to a cell phone or tablet capable of running applications, but only
      a small group (n = 18) reported use of existing mHealth programs for PTSD. Age
      significantly predicted ownership of mHealth devices, but not utilization or
      interest in mHealth applications among device owners. Around 56% to 76% of
      respondents with access indicated that they were interested in trying mHealth
      programs for such issues as anger management, sleep hygiene, and management of
      anxiety symptoms. Findings from this sample suggest that Veterans have adequate
      access to, and interest in, using mHealth applications to warrant continued
      development and evaluation of mobile applications for the treatment of PTSD and
      other mental health conditions. 

PMID- 25373045
TI  - Hybrid simulation improves medical student procedural confidence during EM
      clerkship.
AB  - BACKGROUND: Medical students have limited opportunities to perform and learn
      procedures on live patients. This is particularly concerning at the Uniformed
      Services University of the Health Sciences (USUHS), where graduates may be
      assigned to an operational military unit immediately following completion of
      internship. The authors implemented a new hybrid simulation lab for fourth-year
      medical students at the Uniformed Services University of the Health Sciences
      consisting of procedural skills training for seven core emergency medicine skills
      combined with complex patient cases using high fidelity simulators and
      standardized patients. OBJECTIVES: Measure changes in student procedural skills
      confidence due to the new hybrid simulation curriculum. METHODS: This
      observational study used anonymous 5-point Likert-anchored questionnaires to
      measure student confidence at three different times: immediately before hybrid
      simulation training, immediately after training, and 3 weeks post-training.
      RESULTS: Pretraining student confidence was 3.0 (out of 5) when averaged for all
      seven procedures. This improved to 4.2 immediately after training, and remained
      high (4.1) 3 weeks later at the end of the clerkship. Students retained this
      improved confidence despite performing few procedures on real patients during
      their clerkships. The training demonstrated statistically significant confidence
      improvement for all procedures, except bag-valve mask ventilation. CONCLUSIONS:
      Hybrid simulation training improves student confidence with procedural skills
      during an emergency medicine clerkship.

PMID- 25373046
TI  - High seas to high explosives: the evolution of calcaneus fracture management in
      the military.
AB  - Calcaneus fractures typically occur as a consequence of axial load. In the
      civilian population, this is most often because of motor vehicle accidents or
      falls from height. Early management of these injuries in the military population
      largely mirrored that of civilian surgeons. However, calcaneus fractures
      secondary to underfoot blasts became a significant source of morbidity and
      mortality in World War II. First described in the aftermath of large-scale naval
      battles between metal-deck ships, this "deck-slap" phenomenon is associated with
      high rates of concomitant injuries, infection, and amputation. We review the
      historical and contemporary management of calcaneus fractures by military
      orthopedic surgeons, as well as detailing the unique challenges faced in managing
      the soft-tissue component and associated injuries commonly observed in this
      population. Combat-related calcaneus fractures are associated with very high
      rates of concomitant injuries and extensive soft-tissue wounds. Despite
      significant research and technological advances, functional outcomes following
      these devastating injuries have remained unsatisfying. 

PMID- 25373047
TI  - Non-VA primary care providers' perspectives on comanagement for rural veterans.
AB  - BACKGROUND: Many veterans utilize health care services within and outside of the
      Department of Veterans Affairs (VA). There are limited VA care coordination
      resources for non-VA primary care providers (PCPs), and the non-VA provider
      perspective on caring for veterans is underrepresented. The VA requires Patient
      Aligned Care Teams to coordinate care for veterans across health systems.
      OBJECTIVE: To elicit perspectives of PCPs on caring for veterans who use both VA
      and non-VA health care. METHODS: Qualitative data from semistructured telephone
      interviews were interpreted in the context of quantitative survey results.
      Participants were PCPs in a practice-based research network in 2011. 67 non-VA
      PCPs completed surveys, and descriptive statistics were performed. 21
      semistructured telephone interviews were transcribed and underwent thematic
      analysis. RESULTS: Current communication with VA was viewed as poor, and many
      believed this led to poor patient outcomes. The veteran was identified as the
      main vehicle for information transfer between providers, which was viewed as
      undesirable. Non-VA providers felt they were interacting with VA as a system
      rather than with individual providers. CONCLUSIONS: VA system barriers hinder
      communication between providers, possibly resulting in fragmented care.
      Addressing these barriers will potentially improve patient safety and
      satisfaction.

PMID- 25373048
TI  - Characteristics associated with incidents of family maltreatment among United
      States Air Force families.
AB  - From 2002 until 2007, the United States Air Force (USAF) revised the process of
      determining whether incidents of suspected family maltreatment met the criteria
      for maltreatment. In this study, all reported child maltreatment and partner
      abuse incidents in the USAF from January 2008 to July 2011 were examined to
      determine the extent to which characteristics of victims, offenders, and
      incidents affected whether incidents were determined to have met criteria for
      maltreatment. For both child maltreatment and partner abuse, alleged incidents in
      which offenders used substances and more severe incidents were more likely to
      have met maltreatment criteria than alleged incidents that did not involve
      offender substance use and less severe incidents. However, characteristics of the
      persons involved (e.g., age, gender, military status) were generally unassociated
      with an incident meeting criteria. Consistent with the goals of the criteria
      revisions, these results suggest that the current USAF criteria are associated
      with incident characteristics and not with demographic characteristics of the
      persons involved in the incident. 

PMID- 25373049
TI  - CT positive brain injury in mild TBI patients presenting with normal SAC scores.
AB  - INTRODUCTION: Traumatic brain injury accounts for over 1 million U.S. emergency
      department visits annually. A significant percentage of patients undergo CT scans
      to exclude intracranial bleeds. The Standardized Assessment of Concussion (SAC)
      is designed to rapidly determine whether a concussion has occurred, (0-30 scale,
      where >=25 is considered normal). Although not intended to be used in isolation,
      results in the normal range are considered an indication of low suspicion of
      brain injury. This study evaluated the relationship between CT findings of
      structural injury (CT+) and performance on the SAC. METHODS: We performed a
      prospective observational study on mild head-injured patients presenting to the
      emergency department who underwent CT scans and had SAC evaluations. RESULTS: We
      enrolled 368 patients, of which 66 were read by a neuroradiologist as positive
      (CT+), with an average age of 46.7, and an average Glasgow Coma Scale of 14.85.
      38.2% of these CT+ patients had a SAC score >=25. There were no significant
      differences between time of injury and CT scan or SAC for those with high or low
      SAC scores. Both high and low SAC groups contained similar CT+ abnormalities
      (e.g., hematomas). CONCLUSIONS: These results indicate that a normal SAC score
      alone does not exclude intracranial injury.

PMID- 25373050
TI  - The Israeli Defense Force experience with intraosseous access.
AB  - INTRODUCTION: Obtaining vascular access is of paramount importance in trauma
      care. When peripheral venous access is indicated but cannot be obtained, the
      intraosseous route represents an alternative. The Bone Injection Gun (BIG) is the
      device used for intraosseous access by the Israeli Defense Force (IDF). The
      purpose of this study is to assess the success rate of intraosseous access using
      this device. METHOD: The IDF Trauma Registry from 1999 to 2012 was searched for
      patients for whom at least 1 attempt at intraosseous access was made. RESULTS: 37
      attempts at intraosseous access were identified in 30 patients. Overall success
      rate was 50%. No differences in success rates were identified between different
      care givers. Overall mortality was 87%. CONCLUSION: The use of BIG in the IDF was
      associated with a low success rate at obtaining intraosseous access. Although
      inability to achieve peripheral venous access can be considered an indicator for
      poor prognosis, the high mortality rate for patients treated with BIG can also
      stand for the provider's low confidence in using this tool, making its use a last
      resort. This study serves as an example to ongoing learning process that includes
      data collection, analysis, and improvement, constantly taking place in the IDF.

PMID- 25373051
TI  - Trauma care at a multinational United Kingdom-led Role 3 combat hospital:
      resuscitation outcomes from a multidisciplinary approach.
AB  - Recent conflicts have led significant advancements in casualty care. Facilities
      serving combat wounded operate in challenging environments. Our purpose is to
      describe the multidisciplinary resuscitation algorithm utilized at a United
      Kingdom-led, Role 3 multinational treatment facility in Afghanistan focusing on
      injury severity and in-hospital mortality. METHODS: Data were extracted from our
      prospectively collected trauma registry on military members wounded in action.
      RESULTS: From November 1, 2009 to September 30, 2011, there were 3483 military
      trauma admissions. Common mechanisms of injury were improvised explosive devices
      (48%), followed by gunshot wounds (29%). Most patients (83.1%) had an Injury
      Severity Score (ISS) <15. For patients with complete ISS data, 8.4% had massive
      transfusion and 6.1% had an initial base deficit >5. Patients admitted with signs
      of life had a died of wounds rate of 1.8% with an average 1.2 day hospital stay.
      The mortality rate for patients undergoing massive transfusion was 4.8%, and for
      patients with a base deficit >5, mortality was 12.3%. Severely injured patients
      (ISS > 24) had a mortality rate of 16.5%. CONCLUSION: A systematic,
      multidisciplinary approach to trauma is associated with low in-hospital
      mortality. The outcomes in this study serve as a measure for future care in Role
      3 facilities.

PMID- 25373052
TI  - Do all women with indeterminate pregnancies need a formal ultrasound before
      discharge from the emergency department?
AB  - OBJECTIVE: The identification of ectopic pregnancy is the primary concern for
      pregnant patients with an indeterminate ultrasound (an empty uterus or
      gestational sac). The absence of free fluid and adnexal masses by ultrasound
      combined with the absence of ectopic risk factors are used to place women in a
      "low-risk" category. We believe that women in a "low-risk" category with a beta
      human chorionic gonadotropin (beta-hCG) below 3,000 mIU/mL can be discharged with
      only an emergency department (ED) ultrasound, provided there is 48 to 72 hours
      obstetric follow-up. METHODS: Follow-up encounters from August 2010 to March 2011
      were reviewed. The inclusion criteria were women who only received an ED
      performed indeterminate ultrasound and an acute follow-up appointment with
      concern for ectopic pregnancy. RESULTS: Forty-nine women met inclusion criteria.
      Twenty-nine women (59.2%, 95% CI: 45.4%-73%) had a spontaneous abortion; 18 women
      (36.7%, 95% CI: 23.2%-50.2%) had a normal pregnancy, and 2 women (4.1%, 95% CI:
      1.5%-9.7%) had an ectopic pregnancy. Both ectopic pregnancies had no risk factors
      with beta-hCG values of 96 and 197 mIU/mL. CONCLUSION: This study suggests that
      low-risk indeterminate pregnancies by an ED ultrasound and beta-hCG level <3,000
      mIU/mL can be safely discharged without formal ultrasonography provided a 48 to
      72 hours follow-up with an obstetrician.

PMID- 25373053
TI  - Comparative resuscitation measures for the treatment of desipramine overdose.
AB  - A toxic dose of desipramine (tricyclic antidepressant) causes cardiac arrhythmias
      and ultimately asystole. Resuscitation is difficult and almost always
      unsuccessful. Anecdotal evidence suggests that an infusion of lipid emulsion may
      be an effective treatment. The purpose of this study was to determine the optimal
      combination of lipid rescue and traditional Advanced Cardiac Life Support therapy
      for the treatment of desipramine overdose. We use a prospective, experimental,
      between subjects design with a swine model investigating the effectiveness of the
      drugs and drug combinations administered with cardiopulmonary resuscitation.
      Subjects were randomly assigned to 1 of 8 cardiopulmonary resuscitation/drug
      combination interventions, and the results from each group were compared using an
      analysis of variance and post hoc Tukey where appropriate. The groups that
      received vasopressin were more likely to survive than those that did not receive
      vasopressin, and the groups that received lipid emulsion were more likely to
      survive than those that did not receive lipid emulsion. Vasopressin alone was
      shown to be the most effective treatment in the management of desipramine
      overdose. The results of this study may warrant changes in treatment protocols
      for desipramine overdose. 

PMID- 25373054
TI  - The impact of deployment on COPD in active duty military personnel.
AB  - PURPOSE: To identify trends in chronic obstructive pulmonary disease (COPD)
      diagnoses among active duty U.S. military personnel based on deployment history
      and whether International Classification of Disease, 9th edition (ICD-9) coding
      meet criteria for the diagnosis of COPD. METHODS: A retrospective chart review
      using the electronic medical system was conducted for military personnel
      diagnosed with COPD based on ICD-9 codes for emphysema or chronic obstructive
      lung disease with at least three qualifying outpatient COPD-coded encounters.
      Clinical symptoms, smoking history, pulmonary function testing, and radiographs
      obtained during the diagnostic workup were reviewed. The established diagnosis of
      COPD was analyzed in relation to deployment. RESULTS: A total of 371 patients
      were identified during the study period (2005-2009). Of these patients, 194
      (52.3%) deployed, whereas 177 (47.7%) did not deploy to Southwest Asia since
      2003. Thirty-four percent had no documented smoking history despite the diagnosis
      of COPD. Airway obstruction was identified by spirometry in only 67% of
      individuals diagnosed with COPD. No statistically significant differences in
      pulmonary function testing values were identified between those deployed and
      nondeployed individuals. CONCLUSION: Despite evidence of increased respiratory
      symptoms in deployed military personnel, the impact of deployment on increased
      diagnosis of COPD or severity of disease appears minimal.

PMID- 25373055
TI  - Adolescent mental health and academic functioning: empirical support for
      contrasting models of risk and vulnerability.
AB  - Adolescents in military families contend with normative stressors that are
      universal and exist across social contexts (minority status, family disruptions,
      and social isolation) as well as stressors reflective of their military life
      context (e.g., parental deployment, school transitions, and living outside the
      United States). This study utilizes a social ecological perspective and a stress
      process lens to examine the relationship between multiple risk factors and
      relevant indicators of youth well-being, namely depressive symptoms and academic
      performance, as well as the mediating role of self-efficacy (N = 1,036). Three
      risk models were tested: an additive effects model (each risk factor uniquely
      influences outcomes), a full cumulative effects model (the collection of risk
      factors influences outcomes), a comparative model (a cumulative effects model
      exploring the differential effects of normative and military-related risks). This
      design allowed for the simultaneous examination of multiple risk factors and a
      comparison of alternative perspectives on measuring risk. Each model was
      predictive of depressive symptoms and academic performance through persistence;
      however, each model provides unique findings about the relationship between risk
      factors and youth outcomes. Discussion is provided pertinent to service providers
      and researchers on how risk is conceptualized and suggestions for identifying at
      risk youth. 

PMID- 25373056
TI  - Experience of the Veterans Health Administration in Massachusetts after state
      health care reform.
AB  - Starting in 2006, Massachusetts enacted a series of health insurance reforms that
      successfully led to 96.6% of its population being covered by 2011. As the rest of
      the nation undertakes similar reforms, it is unknown how the Veterans Health
      Administration (VHA), one of many important Federal health care programs, will be
      affected. Our state-level study approach assessed the effects of health reform on
      utilization of VHA services in Massachusetts from 2005 to 2011. Models were
      adjusted for state-level demographic and economic characteristics, including
      health insurance rates, unemployment rates, median household income, poverty
      rates, and percent of population 65 years and older. No statistically significant
      associative change was observed in Massachusetts relative to other states over
      this time period. The findings raise important questions about the continuing
      role of VHA in American health care as health insurance coverage is one of many
      factors that influence decisions on where to seek health care. 

PMID- 25373057
TI  - Considering a relational model for depression in Navy recruits.
AB  - OBJECTIVE: Key variables that have influenced depression in previous research
      were examined in this study including adult attachment, perceived social support,
      sense of belonging, conflict in relationships, and loneliness for their
      relationships in a relational model for depression with U.S. Navy recruits in
      basic training. METHODS: This theory-testing analysis study was part of a larger
      cross-sectional cohort study that examined the factors associated with depression
      in Navy recruits. The sample for this study included 443 recruits. Structural
      equation modeling was used to test the fit of the theoretical model. RESULTS: The
      proposed model explained 49% of the variance in depressive symptoms with
      loneliness and sense of belonging as the strongest indicators of depression.
      CONCLUSIONS: The Navy should consider interventions that increase sense of
      belonging in high risk for depression recruits to decrease loneliness and
      depression and circumvent recruits not completing basic training. The assumption
      that recruits are in close quarters and contact with other people and therefore
      are not lonely and receive adequate social support is not supported. This article
      contributes to advancing the science of mental health in relation to depression
      by considering predictors that are amenable to intervention.

PMID- 25373058
TI  - The incidence of early and recurrent urinary tract infections after midurethral
      sling operations.
AB  - OBJECTIVE: To define the incidence of early and recurrent urinary tract
      infections (RUTIs) in the 12-month postoperative period following midurethral
      sling (MUS) operations and evaluate for risk factors. METHODS: This retrospective
      chart review compiled all urine analyses and urine culture results within 12
      months of MUS surgery on all patients in the years 2006-2012 for which data were
      available. All coincident risk factors were tabulated. Statistical analysis was
      performed using SAS v 9.2 (SAS Institute, Cary, North Carolina). RESULTS: 141 MUS
      procedures were performed in the 6-year time frame utilizing standard antibiotic
      prophylaxis regimens. 133 had adequate data for analysis. 10 patients (7.5%
      confidence intervals [CI] [3.7-12.4]) developed an acute UTI in the first 8 weeks
      postoperatively. 3 of 121 patients (2.3% CI [0.5-5.9]) developed RUTIs in the
      first year following surgery. Bivariate and multiple logistic regression analyses
      of the data did not reveal any risk factors for either isolated postoperative
      UTIs or RUTIs. CONCLUSIONS: This study documents a low incidence of both acute
      and RUTIs in the female population undergoing MUS operations. These results
      support the current recommendations for perioperative prophylactic antibiotics
      for anti-incontinence procedures.

PMID- 25373059
TI  - Standard of care of erectile dysfunction in U.S. Air Force aircrew and active
      duty not on flying status.
AB  - In 2011, over 3,000 active duty U.S. Air Force (USAF) members were prescribed a
      phosphodiesterase inhibitor (PDEI). PDEIs are first-line therapy for treating
      erectile dysfunction and can have significant side effects that could impact
      aircrew performance. In total, 200 eligible subject records were randomly sampled
      from the active duty USAF population of those males filling a prescription for a
      PDEI in June 2011; 100 of those records were from aviators. The electronic
      records were reviewed and scored to determine if USAF aeromedical standards for
      prescribing PDEIs were followed, with a minimum score of 0 for no standards met
      and a maximum of 3 for all standards met. The average score for both groups was
      1, with no significant difference between the group scores. A proper aeromedical
      disposition was documented in 67% of the aviator records. Although there was no
      significant difference in standard of care for aviators and nonaviators, the
      overall documented standard of care was poor. Lack of documentation was the
      primary reason for the low scores and the low percentage of properly rendered
      aeromedical dispositions. Proper medical record documentation is important for
      evaluating quality of care and ensuring compliance with regulations in an Air
      Force aviator population. 

PMID- 25373060
TI  - Effects of personal and occupational stress on injuries in a young, physically
      active population: a survey of military personnel.
AB  - The aim of this study was to document risk factors for any injury and sports- and
      exercise-related injuries, including personal and occupational stress among
      active duty service members (SMs) in the Air Force, Army, Marine Corps, and Navy.
      A total of 10,692 SMs completed the April 2008 Status of Forces Survey of Active
      Duty Members. The survey asked about demographics, personal stress and
      occupational stress, injuries from any cause, and participation in sports- and
      exercise- related activities in the past year. The survey used a complex sampling
      procedure to create a representative sample of SMs. Logistic regression was used
      to examine the associations of injury outcomes with potential risk factors. 49%
      of SMs sought medical care for an injury in the past year and 25% sustained a
      sports- and exercise-related activities injury. Odds of injury were higher for
      the Army and Marine Corps than for the Air Force or Navy. This survey showed that
      higher personal and occupational stress was associated with higher risks of
      injury. SMs who experienced higher levels of personal or occupational stress
      reported higher risks of injuries. The effects of stress reduction programs on
      injury risks should be evaluated in military and other young physically active
      populations. 

PMID- 25373061
TI  - Utility of a sports medicine model in military combat concussion and
      musculoskeletal restoration care.
AB  - Combat-related concussions are significant sources of injury and morbidity among
      deployed military service members. Musculoskeletal injury also is one of the most
      prevalent battle and nonbattle-related deployed injury types. Both injuries
      threaten the service member's physical condition as well as unit and mission
      readiness due to reduced duty status or evacuation from military theater of
      operations. In August 2010, the Concussion Restoration Care Center (CRCC) was
      established at Camp Leatherneck, Afghanistan, to address the need for consistent
      and specialized evaluation and care of concussion and musculoskeletal injury.
      This performance improvement effort examined evaluation and treatment of
      concussion and musculoskeletal injury at the CRCC. Among 4,947 military personnel
      evaluated at the CRCC between August 2010 and May 2013, 97.9% were returned to
      duty and retained in theater. Members averaged 10 to 12 days of limited duty
      status to achieve complete recovery. Concussion injury was secondary to blast
      injury in 90% of cases. Sport/recreation, occupational, and other accidental
      injuries each represented 30% of the musculoskeletal injuries with only 10%
      reported as result of combat. The utilization patterns and outcome measures
      demonstrate the success and utility of a multidisciplinary clinical model of care
      for these two types of injuries in the far-forward deployed setting. 

PMID- 25373062
TI  - Cardiovascular and cerebrovascular responses to progressive central hypovolemia
      in young smokers: a preliminary study.
AB  - The purpose of this study was to describe cardiovascular and cerebrovascular
      responses of smokers and nonsmokers to progressive central hypovolemia. Twenty
      subjects participated (equal male and female). We recorded the electrocardiogram,
      beat-to-beat arterial pressure (Finometer), cerebral blood velocity of the middle
      cerebral artery (transcranial Doppler), and end-tidal CO2. Lower body negative
      pressure (LBNP) was applied at 3 mm Hg . min(-1) for 20 minutes to an ending
      pressure of -60 mm Hg, and data were averaged in 2-minute bins. Arterial
      pressures were similar between groups at baseline, but heart rates tended to be
      higher, and stroke volumes and cerebral velocities tended to be lower in smokers
      at baseline and during LBNP (all p >= 0.17). Heart rates increased, and arterial
      pressures, stroke volumes, and cerebral velocities decreased during LBNP (all p
      <= 0.05), but responses were not different between smokers and nonsmokers. During
      the final stage of LBNP, systolic pressures and mean middle cerebral artery
      velocities were substantially lower in smokers than nonsmokers: these preliminary
      data may suggest clinical relevance of smoking status, but the magnitude of
      differences between groups were not distinguishable statistically. We therefore
      conclude that smokers and nonsmokers respond similarly to progressive central
      hypovolemia. 

PMID- 25373063
TI  - Priorities of legislatively active veteran services organizations: a content
      analysis and review for health promotion initiatives.
AB  - Military and Veterans Service Organizations (MVSOs) have a unique opportunity to
      influence legislation and advocate for the interests of their members. However,
      little is known about what legislative priorities MVSOs see as important.
      Understanding the legislative priorities of MVSOs can inform efforts by health
      scientists to promote policy and laws designed to improve the health of our
      nation's veterans. Using a mixed methods approach, we conducted a thematic
      analysis of legislative priorities MVSOs promote with their legislative agendas.
      Most commonly, MVSOs addressed issues related to disability evaluations and
      ratings with the Veterans Administration and access to Veterans Administration
      services. Other common themes identified as priorities include benefits such as
      retirement, education, housing assistance for veterans, and TRICARE benefits.
      Findings highlight the broad range of topics MVSOs identify as legislative
      priorities as well as some health issues that receive relatively limited
      attention. 

PMID- 25373064
TI  - Heat tolerance testing: association between heat intolerance and anthropometric
      and fitness measurements.
AB  - This study investigated associations between heat intolerance, as determined by
      performance on a heat tolerance test (HTT), and anthropometric measurements (body
      surface-to-mass ratio, percent body fat, body mass index, and waist
      circumference) and cardiorespiratory fitness (maximal oxygen uptake [VO2max]).
      Relationships between predictive variables and specific physiological
      measurements recorded during the HTT were examined. A total of 34 male and 12
      female participants, recruited from the military community, underwent
      anthropometric measurements, a maximal aerobic exercise test, and a standardized
      HTT, which consisted of walking on a treadmill at 5 km/h at 2% grade for 120
      minutes at 40 degrees C and 40% relative humidity. VO2max negatively correlated
      with maximum core temperature (r = -0.30, p < 0.05) and heart rate (HR) (r = 
      0.48, p < 0.01) although percent body fat showed a positive correlation with
      maximum HR (r = 0.36, p < 0.05). VO2max was the only independent attribute that
      significantly influenced both the maximum HR and core temperature attained during
      HTT. Logistic regression analyses indicated that VO2max was the only independent
      parameter (OR = 0.89, p = 0.026) that significantly contributed to overall HTT
      performance. Low cardiorespiratory fitness was associated with heat intolerance,
      as defined by HTT performance, and can be addressed as a preventative measure for
      exertional heat illness. This study provides further evidence that the HTT can be
      an effective tool for assessment of thermoregulatory patterns. 

PMID- 25373065
TI  - Utilization of telemedicine in the U.S. military in a deployed setting.
AB  - BACKGROUND: A retrospective evaluation of the Department of Defense
      teledermatology consultation program from 2004 to 2012 was performed, focusing on
      clinical application and outcome measures such as consult volume, response time,
      and medical evacuation status. METHODS: A retrospective review of the
      teledermatology program between 2004 and 2012 was evaluated based on defined
      outcome measures. In addition, 658 teledermatology cases were reviewed to assess
      how the program was utilized by health care providers from 2011 to 2012. RESULTS:
      As high as 98% of the teledermatology consults were answered within 24 hours, and
      23% of consults within 1 hour. The most common final diagnoses included
      eczematous dermatitis, contact dermatitis, and evaluation for nonmelanoma skin
      cancer. The most common medications recommended included topical corticosteroids,
      oral antibiotics, antihistamines, and emollients. Biopsy was most commonly
      recommended for further evaluation. Following teleconsultation, 46 dermatologic
      evacuations were "avoided" as the patient was not evacuated based on the
      consultants' recommendation. Consultants' recommendations to the referring
      provider "facilitated" 41 evacuations. CONCLUSION: Telemedicine in the U.S.
      military has provided valuable dermatology support to providers in remote
      locations by delivering appropriate and timely consultation for military service
      members and coalition partners. In addition to avoiding unnecessary medical
      evacuations, the program facilitated appropriate evacuations that may otherwise
      have been delayed.

PMID- 25373066
TI  - Stigma and barriers to accessing mental health services perceived by Air Force
      nursing personnel.
AB  - We investigated perceptions of stigma and barriers associated with accessing
      mental health services among active component U.S. Air Force officer and enlisted
      nursing personnel (N = 211). The Britt and Hoge et al Stigma scale and Hoge et al
      Barriers to Care scale were administered via an anonymous, online survey. Stigma
      items pertained to concerns that might affect decisions to seek mental health
      treatment. Most of the sample agreed with the items "Members of my unit might
      have less confidence in me" and "My unit leadership might treat me differently."
      Approximately 20% to 46% agreed with the other four stigma items. Officer nursing
      personnel were significantly more likely than enlisted to agree that accessing
      mental health services would be embarrassing, harm their career, or cause leaders
      to blame them for the problem (p <= 0.03 for each comparison). Getting time off
      from work for treatment and scheduling appointments were perceived as barriers by
      41% and 21% of respondents, respectively. We conclude that proportions of Air
      Force nursing personnel reporting concerns about potential stigmatizing
      consequences of seeking mental health care are substantial and similar to ranges
      previously reported by military service members screening positive for mental
      health problems after deployment. 

PMID- 25373068
TI  - Veterans' service utilization and associated costs following participation in
      dialectical behavior therapy: a preliminary investigation.
AB  - CONTEXT: Dialectical Behavior Therapy (DBT) is an evidence-based therapy
      developed for the treatment of suicidal behaviors and disorders characterized by
      emotional and behavioral dyscontrol that is effective in veteran populations. The
      impact of DBT on veterans' Veterans Affairs (VA) service utilization and cost is
      unknown. EVIDENCE ACQUISITION: This study evaluated the impact of DBT in a VA
      outpatient mental health setting on VA service utilization and cost of services.
      Veterans treated for symptoms of Borderline Personality Disorder, who had
      completed at least 6 months of the DBT program were sampled (N = 41). Use of
      physical and mental health services during the years prior and following DBT was
      assessed using medical record information. RESULTS: There was a significant
      decrease in mental health service utilization. Psychiatric hospitalization
      dropped in half, and for those with a hospitalization, length of stay decreased
      significantly. Direct costs associated with all health care were significantly
      reduced. CONCLUSION: Changes in service utilization resulted in a significant
      reduction in direct costs of providing care to veterans with symptoms of
      Borderline Personality Disorder. Additional research is needed to compare the
      reduction in overall costs to the cost of implementing DBT and to compare these
      changes to a control group.

PMID- 25373067
TI  - Measuring intravenous cannulation skills of practical nursing students using
      rubber mannequin intravenous training arms.
AB  - This study examined the effectiveness of two training methods for peripheral
      intravenous (IV) cannulation; one using rubber mannequin IV training arms, and
      the other consisting of students performing the procedure on each other. Two
      hundred-sixty Phase II Army Practical Nursing students were randomized into two
      groups and trained to perform an IV cannulation procedure. All students watched a
      12-minute training video covering standard IV placement procedures. Afterward,
      both groups practiced the procedure for an hour according to their assigned
      group. Students were then tested on IV placement in a live human arm using a 14
      item testing instrument in three trials that were scored pass/fail. There was no
      difference in the groups' performance of the IV procedure on the first attempt:
      51.7% (n = 92) of the human arm group passed the test, and 48.3% (n = 86) of the
      rubber mannequin group passed the test (p = 0.074). These data suggest that using
      rubber mannequin IV arms for IV skills training may be just as effective as
      training students using traditional methods. In addition, using simulation
      provides an extra benefit of reducing risks associated with learning the
      procedure on a fellow student. 

PMID- 25373069
TI  - Investigation of an outbreak of anemia cases at an Army trinitrotoluene munitions
      production plant from 2004 to 2005 and subsequent surveillance 2005-2013.
AB  - OBJECTIVE: Investigate an outbreak of anemia that occurred at an Army
      trinitrotoluene (TNT) munitions production facility in 2004-2005 and describe
      subsequent medical surveillance efforts between 2005 and 2013. METHODS: A
      retrospective, cross-sectional investigation of anemia cases and exposure levels
      was conducted to target corrective engineering and administrative changes needed
      to reduce TNT levels and anemia cases. RESULTS: Mean TNT exposure levels
      decreased from 1.2 to 0.08 mg/m(3) between 2004 and 2012, but the trend was not
      statistically significant. Anemia cases rose from 17 to 38 between 2004 and 2011
      and cases declined from 4 to 0 between 2012 and 2013. The overall trend in cases
      was not statistically significant. CONCLUSIONS: TNT levels rose at a munitions
      plant until ventilation changes reduced exposures. Despite this, anemia cases
      continued to rise until the commander held workers accountable for failing to
      wear PPE and motivated them to wear respirators to avoid a loss in pay. The case
      definition of anemia was revised to be consistent with the case definition used
      by private physicians who practiced in the community. Better coveralls are
      needed, which are easy to wear, reduce static discharge, and prevent TNT skin
      absorption.

PMID- 25373070
TI  - Assessment of revised recruitment standards for asthma in the Australian Defence
      Force.
AB  - OBJECTIVE: To assess the impact of relaxed asthma recruitment standards adopted
      by the Australian Defence Force in 2007. METHODS: A retrospective audit was
      conducted on clinical and administrative data for recruits, with and without mild
      asthma, in their first year of service. RESULTS: There was no evidence that mild
      asthmatics experienced worse outcomes than nonasthmatic recruits. Mild asthmatics
      had fewer illnesses and restricted duty days and were less costly compared to
      other recruits. There was no difference in the rate of discharge (attrition)
      between those with and without mild asthma. CONCLUSIONS: The revised recruitment
      standards for asthma in the Australian Defence Force have not resulted in
      unanticipated medical or administrative costs to the organization. Health and
      administrative outcomes differed little between mild asthmatics and nonasthmatic
      recruits in their first 12 months of service.

PMID- 25373071
TI  - Assessment of a postdeployment Yellow Ribbon Reintegration Program for National
      Guard members and supporters.
AB  - The Yellow Ribbon Reintegration Program (YRRP) was created to meet the needs of
      National Guard members and their families throughout the deployment cycle. This
      study examined the perceived utility of the YRRP's delivery of information and
      assistance during the postdeployment reintegration period by National Guard
      members and accompanying supporters who were mostly spouses. Over 22 months, from
      10 YRRP events, 683 service members and 411 supporters completed questionnaires
      immediately after the YRRP. We analyzed questions on information and avenues for
      help, timeliness and concerns related to education, employment, legal, family,
      and health. Service members and supporters most often endorsed information
      delivery on education being met (76.8% and 78.2%, respectively) and were least
      likely to endorse legal information delivery (63.5% and 60%, respectively).
      Significantly more supporters than service members (p < 0.0001) reported that the
      YRRP was the first time they learned of available services across all domains.
      Service members were significantly more likely than supporters to report concerns
      about education, employment, and health, while supporters were significantly more
      likely to report concerns about family. Results suggest the YRRP fills gaps in
      supporter knowledge and provides needed information and resources to most
      National Guard families 2 to 4 months after a deployment. 

PMID- 25373072
TI  - "American angels of mercy" and the Russo-Japanese War.

PMID- 25373073
TI  - Surgical dental treatment for military personnel: where and when?--a case report.
AB  - INTRODUCTION: Oral health is essential for combat readiness. The classification
      for combat readiness includes the Dental Fitness Categories, which are used to
      estimate a soldier's need for emergency dental care while deployed overseas. When
      the issue at hand is in regard to unerupted or additional teeth, the treating
      dentist faces a difficult decision since there is no evidence-based practice
      guidelines. CASE REPORT: An otherwise healthy 20 year-old soldier initially
      presented to his general physician (Role I) with toothache in the lower jaw. The
      initial referral to a general dentist (Role II) led to a diagnosis of an
      additional tooth 45; therefore, he was transferred to the oral surgeon (Role
      III). A computed tomography scan revealed fully retained besides the additional
      45, wisdom teeth, and additional wisdom teeth, as well as retained tooth 23.
      After careful consideration, osteotomies of all retained teeth were performed
      under general anesthesia. A titanium miniplate was placed for stabilization.
      DISCUSSION: Despite variability among dentists in assigning a particular Dental
      Fitness Class, the clinical and radiologic examination must take into account
      treatment options that may become necessary for unerupted and retained teeth.

PMID- 25373074
TI  - How to reconstruct an upper full-thickness abdomen wall defect in austere
      environment? Interests of the pedicled myofascial latissimis dorsi flap.
AB  - Upper abdominal wall defects secondary to trauma are not amenable to immediate
      closure in most cases. After a primary coverage, the definitive reconstruction
      can be done at a later date, using prosthetic mesh or flap. The majority of these
      complex procedures is, however, not available in the austere environment. The
      authors report a clinical case of upper full-thickness defects of the abdominal
      wall secondary to an explosion in Afghanistan. The patient was managed by a
      French Forward Surgical Team. The defect was immediately reconstructed in a one
      stage surgery using a pedicled myofascial latissimus dorsi flap with good
      functional results. The pedicled latissimus dorsi flap is commonly used for
      coverage of both extrathoracic and intrathoracic defects. It is, therefore,
      possible to extend the harvesting of the muscle to the thoracolumbar fascia and
      the posterior third of the iliac crest. It provides a very large flap to cover an
      upper full-thickness abdomen wall defect. The harvest technique is simple, short,
      and largely accessible to a general surgeon. It provides immediate and definitive
      closure with a short hospital stay, what is clearly adapted in austere
      environment. 

PMID- 25373075
TI  - Painful ophthalmoplegia: a case of Tolosa-Hunt syndrome.
AB  - Unilateral painful opthalmoplegia involving the third, fourth, or sixth cranial
      nerve in association with a retro-orbital mass should be evaluated for
      rheumatologic conditions and malignancy. The assessment may require a biopsy of
      the mass. Once cancer and autoimmune conditions such as sarcoidosis have been
      ruled out, Tolosa-Hunt should be considered. Tolosa-Hunt is a rare condition that
      presents as an acute unilateral eye pain with motor dysfunction and responds to
      prolonged treatment with corticosteroids. Presented is a case of Tolosa-Hunt
      syndrome. 

PMID- 25373076
TI  - Monitoring cerebral hemodynamics following optogenetic stimulation via optical
      coherence tomography.
AB  - In this article, spectral domain optical coherence tomography is used to measure
      the hemodynamic response induced by optogenetic stimulation in the somatosensory
      cortex of transgenic mice. By analyzing the 3-D angiograms and Doppler
      measurements produced by coherence tomography, we observed significant increase
      in blood flow as a result of increased vessel diameter and blood velocity
      following optical stimulation of cortical neurons. Such distinct responses were
      not observed in control experiments where the brain of wild-type mice were
      exposed to the same light pulses. 

PMID- 25373077
TI  - Advanced model-based control studies for the induction and maintenance of
      intravenous anaesthesia.
AB  - This paper describes strategies toward model-based automation of intravenous
      anaesthesia employing advanced control techniques. In particular, based on a
      detailed compartmental mathematical model featuring pharmacokinetic and
      pharmacodynamics information, two alternative model predictive control strategies
      are presented: a model predictive control strategy, based on online optimization,
      the extended predictive self-adaptive control and a multiparametric control
      strategy based on offline optimization, the multiparametric model predictive
      control. The multiparametric features to account for the effect of nonlinearity
      and the impact of estimation are also described. The control strategies are
      tested on a set of 12 virtually generated patient models for the regulation of
      the depth of anaesthesia by means of the bispectral index (BIS) using Propofol as
      the administrated anaesthetic. The simulations show fast response, suitability of
      dose, and robustness to induce and maintain the desired BIS setpoint. 

PMID- 25373078
TI  - Real-time task recognition in cataract surgery videos using adaptive
      spatiotemporal polynomials.
AB  - This paper introduces a new algorithm for recognizing surgical tasks in real-time
      in a video stream. The goal is to communicate information to the surgeon in due
      time during a video-monitored surgery. The proposed algorithm is applied to
      cataract surgery, which is the most common eye surgery. To compensate for eye
      motion and zoom level variations, cataract surgery videos are first normalized.
      Then, the motion content of short video subsequences is characterized with
      spatiotemporal polynomials: a multiscale motion characterization based on
      adaptive spatiotemporal polynomials is presented. The proposed solution is
      particularly suited to characterize deformable moving objects with fuzzy borders,
      which are typically found in surgical videos. Given a target surgical task, the
      system is trained to identify which spatiotemporal polynomials are usually
      extracted from videos when and only when this task is being performed. These key
      spatiotemporal polynomials are then searched in new videos to recognize the
      target surgical task. For improved performances, the system jointly adapts the
      spatiotemporal polynomial basis and identifies the key spatiotemporal polynomials
      using the multiple-instance learning paradigm. The proposed system runs in real
      time and outperforms the previous solution from our group, both for surgical task
      recognition ( Az = 0.851 on average, as opposed to Az = 0.794 previously) and for
      the joint segmentation and recognition of surgical tasks ( Az = 0.856 on average,
      as opposed to Az = 0.832 previously). 

PMID- 25373079
TI  - Tree-based Morse regions: a topological approach to local feature detection.
AB  - This paper introduces a topological approach to local invariant feature detection
      motivated by Morse theory. We use the critical points of the graph of the
      intensity image, revealing directly the topology information as initial interest
      points. Critical points are selected from what we call a tree-based shape-space.
      In particular, they are selected from both the connected components of the upper
      level sets of the image (the Max-tree) and those of the lower level sets (the Min
      tree). They correspond to specific nodes on those two trees: 1) to the leaves
      (extrema) and 2) to the nodes having bifurcation (saddle points). We then
      associate to each critical point the largest region that contains it and is
      topologically equivalent in its tree. We call such largest regions the tree-based
      Morse regions (TBMRs). The TBMR can be seen as a variant of maximally stable
      extremal region (MSER), which are contrasted regions. Contrarily to MSER, TBMR
      relies only on topological information and thus fully inherit the invariance
      properties of the space of shapes (e.g., invariance to affine contrast changes
      and covariance to continuous transformations). In particular, TBMR extracts the
      regions independently of the contrast, which makes it truly contrast invariant.
      Furthermore, it is quasi-parameter free. TBMR extraction is fast, having the same
      complexity as MSER. Experimentally, TBMR achieves a repeatability on par with
      state-of-the-art methods, but obtains a significantly higher number of features.
      Both the accuracy and robustness of TBMR are demonstrated by applications to
      image registration and 3D reconstruction.

PMID- 25373080
TI  - Local symmetry detection in natural images using a particle filtering approach.
AB  - In this paper, we propose an algorithm to detect smooth local symmetries and
      contours of ribbon-like objects in natural images. The detection is formulated as
      a spatial tracking task using a particle filtering approach, extracting one part
      of a structure at a time. Using an adaptive local geometric model, the method can
      detect straight reflection symmetries in perfectly symmetrical objects as well as
      smooth local symmetries in curved elongated objects. In addition, the proposed
      approach jointly estimates spine and contours, making it possible to generate
      back ribbon objects. Experiments for local symmetry detection have been conducted
      on a recent extension of the Berkeley segmentation data sets. We also show that
      it is possible to retrieve specific geometrical objects using intuitive prior
      structural information.

PMID- 25373081
TI  - Learning multiple relative attributes with humans in the loop.
AB  - Semantic attributes have been recognized as a more spontaneous manner to describe
      and annotate image content. It is widely accepted that image annotation using
      semantic attributes is a significant improvement to the traditional binary or
      multiclass annotation due to its naturally continuous and relative properties.
      Though useful, existing approaches rely on an abundant supervision and high
      quality training data, which limit their applicability. Two standard methods to
      overcome small amounts of guidance and low-quality training data are transfer and
      active learning. In the context of relative attributes, this would entail
      learning multiple relative attributes simultaneously and actively querying a
      human for additional information. This paper addresses the two main limitations
      in existing work: 1) it actively adds humans to the learning loop so that minimal
      additional guidance can be given and 2) it learns multiple relative attributes
      simultaneously and thereby leverages dependence amongst them. In this paper, we
      formulate a joint active learning to rank framework with pairwise supervision to
      achieve these two aims, which also has other benefits such as the ability to be
      kernelized. The proposed framework optimizes over a set of ranking functions
      (measuring the strength of the presence of attributes) simultaneously and
      dependently on each other. The proposed pairwise queries take the form of which
      one of these two pictures is more natural? These queries can be easily answered
      by humans. Extensive empirical study on real image data sets shows that our
      proposed method, compared with several state-of-the-art methods, achieves
      superior retrieval performance while requires significantly less human inputs.

PMID- 25373082
TI  - Robustifying descriptor instability using Fisher vectors.
AB  - Many computer vision applications, including image classification, matching, and
      retrieval use global image representations, such as the Fisher vector, to encode
      a set of local image patches. To describe these patches, many local descriptors
      have been designed to be robust against lighting changes and noise. However,
      local image descriptors are unstable when the underlying image signal is low.
      Such low-signal patches are sensitive to small image perturbations, which might
      come e.g., from camera noise or lighting effects. In this paper, we first
      quantify the relation between the signal strength of a patch and the instability
      of that patch, and second, we extend the standard Fisher vector framework to
      explicitly take the descriptor instabilities into account. In comparison to
      common approaches to dealing with descriptor instabilities, our results show that
      modeling local descriptor instability is beneficial for object matching, image
      retrieval, and classification.

PMID- 25373083
TI  - Inverse rendering of Lambertian surfaces using subspace methods.
AB  - We propose a vector space approach for inverse rendering of a Lambertian convex
      object with distant light sources. In this problem, the texture of the object and
      arbitrary lightings are both to be recovered from multiple images of the object
      and its 3D model. Our work is motivated by the observation that all possible
      images of a Lambertian object lie around a low-dimensional linear subspace
      spanned by the first few spherical harmonics. The inverse rendering can therefore
      be formulated as a matrix factorization, in which the basis of the subspace is
      encoded in a spherical harmonic matrix S associated with the object's geometry. A
      necessary and sufficient condition on S for unique factorization is derived with
      an introduction to a new notion of matrix rank called nonseparable full rank. A
      singular value decomposition-based algorithm for exact factorization in the
      noiseless case is introduced. In the presence of noise, two algorithms, namely,
      alternating and optimization based are proposed to deal with two different types
      of noise. A random sample consensus-based algorithm is introduced to reduce the
      size of the optimization problem, which is equal to the number of pixels in each
      image. Implementations of the proposed algorithms are done on a real data set.

PMID- 25373084
TI  - Implicit B-spline surface reconstruction.
AB  - This paper presents a fast and flexible curve, and surface reconstruction
      technique based on implicit B-spline. This representation does not require any
      parameterization and it is locally supported. This fact has been exploited in
      this paper to propose a reconstruction technique through solving a sparse system
      of equations. This method is further accelerated to reduce the dimension to the
      active control lattice. Moreover, the surface smoothness and user interaction are
      allowed for controlling the surface. Finally, a novel weighting technique has
      been introduced in order to blend small patches and smooth them in the
      overlapping regions. The whole framework is very fast and efficient and can
      handle large cloud of points with very low computational cost. The experimental
      results show the flexibility and accuracy of the proposed algorithm to describe
      objects with complex topologies. Comparisons with other fitting methods highlight
      the superiority of the proposed approach in the presence of noise and missing
      data. 

PMID- 25373085
TI  - Fast global image smoothing based on weighted least squares.
AB  - This paper presents an efficient technique for performing a spatially
      inhomogeneous edge-preserving image smoothing, called fast global smoother.
      Focusing on sparse Laplacian matrices consisting of a data term and a prior term
      (typically defined using four or eight neighbors for 2D image), our approach
      efficiently solves such global objective functions. In particular, we approximate
      the solution of the memory-and computation-intensive large linear system, defined
      over a d-dimensional spatial domain, by solving a sequence of 1D subsystems. Our
      separable implementation enables applying a linear-time tridiagonal matrix
      algorithm to solve d three-point Laplacian matrices iteratively. Our approach
      combines the best of two paradigms, i.e., efficient edge-preserving filters and
      optimization-based smoothing. Our method has a comparable runtime to the fast
      edge-preserving filters, but its global optimization formulation overcomes many
      limitations of the local filtering approaches. Our method also achieves high
      quality results as the state-of-the-art optimization-based techniques, but runs
      ~10-30 times faster. Besides, considering the flexibility in defining an
      objective function, we further propose generalized fast algorithms that perform
      Lgamma norm smoothing (0 < gamma < 2) and support an aggregated (robust) data
      term for handling imprecise data constraints. We demonstrate the effectiveness
      and efficiency of our techniques in a range of image processing and computer
      graphics applications.

PMID- 25373086
TI  - Nutritional armor: omega-3 for the warfighter.

PMID- 25373087
TI  - The effect of omega-3 fatty acids on biomarkers of inflammation: a rapid evidence
      assessment of the literature.
AB  - INTRODUCTION: Previous studies of omega-3 fatty acids report improved outcomes
      where inflammation is a key factor. The objective of this systematic review is to
      evaluate effects of omega-3s on inflammatory biomarkers. METHODS: Randomized
      clinical studies that measured the influence of omega-3 fatty acids on
      inflammatory biomarkers were identified using a comprehensive search. Eligible
      studies were rated with the American Dietetic Association Evidence Analysis
      Manual and Grading of Recommendations, Assessment, Development and Evaluation
      (GRADE) process to examine study quality and risk/benefit. RESULTS: 112 studies
      were included. Over 65% reported statistically significant effects. The majority
      were scored as low risk of bias (high quality) and scored strong (cardiac
      populations and critically ill) to weak (Alzheimer's Disease,
      hypertriglyceridemia/diabetes, and obesity) on the risk/benefit ratio evidence
      for modulation of inflammatory biomarkers. There was inadequate data to determine
      a GRADE for inflammatory biomarker studies for some conditions (healthy
      individuals, rheumatoid arthritis, metabolic syndrome, renal disease, pregnancy,
      or children). CONCLUSION: Clinical literature on the effects of omega-3 fatty
      acids on inflammatory biomarkers contains mostly small sample sizes, is neutral
      to high quality, and report mixed effects. Larger studies examining dose and
      delivery are needed.

PMID- 25373088
TI  - Nutritional armor in evolution: docosahexaenoic acid as a determinant of neural,
      evolution and hominid brain development.
AB  - The aim of this article is to draw attention to the special significance of
      docosahexaenoic acid (DHA) in the brain, the potential relevance of its abundance
      to the evolution of the brain in past history, and now the relevance of paucity
      in the food supply to the rise in mental ill-health. Membrane lipids of
      photoreceptors, synapses, and neurons over the last 600 million years contained
      consistent and similarly high levels of DHA despite wide genomic change. The
      consistency is despite the DHA precursor differing only by 2 protons. This
      striking conservation is an example of Darwin's "Conditions of Existence," which
      he described as the higher force in evolution. A purpose of this article is to
      suggest that the present paradigm of food production currently based on protein
      requirements, should change to serve the specific lipid needs of the brain to
      address the rise in mental ill-health.(1.) 

PMID- 25373089
TI  - Dietary omega-3 and omega-6 fatty acids compete in producing tissue compositions
      and tissue responses.
AB  - Serious food-related health disorders may be prevented by recognizing the
      molecular processes that connect the dietary intake of vitamin-like fatty acids
      to tissue accumulation of precursors of potent hormone-like compounds that cause
      harmful tissue responses. Conversion of dietary 18-carbon omega-3 and omega-6
      polyunsaturated fatty acids to tissue 20- and 22-carbon highly unsaturated fatty
      acids (HUFAs) is catalyzed by promiscuous enzymes that allow different types of
      fatty acid to compete among each other for accumulation in tissue HUFA. As a
      result, food choices strongly influence the types of accumulated tissue HUFA.
      However, the conversion of tissue HUFA to active hormones and their receptor
      mediated actions occurs with discriminating enzymes and receptors that give more
      intense responses for the omega-6 and omega-3 hormones. Undesired chronic health
      disorders, which are made worse by excessive omega-6 hormone actions, can be
      prevented by eating more omega-3 fats, less omega-6 fats, and fewer calories per
      meal. 

PMID- 25373090
TI  - Omega-3 fatty acid biochemistry: perspectives from human nutrition.
AB  - The possibility that western diets poor in omega-3 and rich in omega-6 fatty
      acids contribute to the increasing burden of chronic diseases including
      neurological problems is becoming recognized. Modern, westernized diets provide
      80 to 90% of polyunsaturated fatty acids as omega-6 linoleic acid (LA) and are
      depleted in omega-3 fatty acids, giving a distorted balance of LA to alpha
      linoleic acid, and to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
      LA intakes exceed Delta-6 desaturase needs for maximal activity. LA accumulates
      in blood and tissue lipids with increasing intake, and this exacerbates
      competition between LA and limited omega-3 fatty acids for metabolism and
      acylation into tissue lipids. Increasing EPA and DHA intake decreases tissue
      omega-6 fatty acids while also providing EPA and DHA. However, strategies for EPA
      and DHA supplementation do not address potential underlying problems of omega-6
      and omega-3 fatty acid imbalance in the food supply. 

PMID- 25373091
TI  - Nutritional armor for the injured warfighter: omega-3 fatty acids in surgery,
      trauma, and intensive care.
AB  - Nutrients have traditionally been viewed as a means to provide basic energy for
      cellular homeostasis and amino acids for protein synthesis in all humans. Young,
      healthy men and women in the military today are presumed to be well nourished and
      mentally and physically fit to perform their duties in austere environments.
      Exposure to high-intensity projectiles, blast injuries, and other wounds of war,
      however, is an everyday occurrence during deployment that potentially challenges
      all homeostatic mechanisms. After sustaining such devastating injuries,
      critically ill, surgical, and trauma patients are in a constant dynamic state
      between the systemic inflammatory response syndrome (and compensatory anti
      inflammatory response syndrome. Compelling evidence supports both immune and
      metabolic response modulation by specific nutrients, including omega-3 fatty
      acids, primarily eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The
      concept of providing nutrients as therapeutic rather than supportive agents to
      meet the basic cellular caloric and metabolic demands requires a major paradigm
      shift. Although the exact route and dose of these metabolically active lipids has
      yet to be determined, data from large clinical studies of cellular ex-vivo
      experiments in patients support the liberal use of eicosapentaenoic acid and
      docosahexaenoic acid in the setting of trauma, surgery, and intensive care. 

PMID- 25373093
TI  - Neuroprotection by docosahexaenoic acid in brain injury.
AB  - Docosahexaenoic acid (DHA, 22:6 n-3) is an omega-3 polyunsaturated fatty acid
      highly enriched in the brain and is recognized as an essential nutrient for
      proper development of brain function. Common brain injuries often cause lifelong
      neurological and cognitive impairments, especially in learning and memory.
      Optimizing the nutritional DHA status in neural tissues may allow significantly
      improved resilience for the central nervous system to injury and optimized
      recovery. This article discusses neuroprotective effects of DHA, which are
      potentially important for improving injury outcome, thus reducing the risk of
      lifelong neurological impairment associated with brain injury. 

PMID- 25373094
TI  - The potential for DHA to mitigate mild traumatic brain injury.
AB  - Scientific knowledge of omega-3 fatty acids (FAs) has grown in the last decade to
      a greater understanding of their mechanisms of action and their potential
      therapeutic effects. Omega-3 FAs have shown therapeutic potential with respect to
      hyperlipidemia, depression, attention-deficit hyperactivity disorder, and mild
      cognitive impairment. Laboratory evidence and clinical interest have grown such
      that omega-3 FAs have now assumed a role in concussion management. This has
      coincided with recent research that has also helped to increase the scientific
      understanding of cerebral concussion; although concussion or mild traumatic brain
      injury was assumed to be a malfunctioning brain without anatomical damage, we now
      know that there is the potential for damage and dysfunction at the cellular and
      microstructural levels. Specifically, with concussion abnormal metabolism of
      glucose may occur and intracellular mitochondrial dysfunction can persist for
      several days. In this article, we discuss the role of omega-3 FAs, particularly
      docosahexaenoic acid, in concussion management. 

PMID- 25373092
TI  - Long-chain omega-3 fatty acids and optimization of cognitive performance.
AB  - Low consumption of the omega-3 fatty acids, eicosapentaenoic and docosahexaenonic
      acids, is linked to delayed brain development and, in late life, increased risk
      for Alzheimer's disease. The current review focuses on cognitive functioning
      during midlife and summarizes available scientific evidence relevant to the
      hypothesis that adequate dietary consumption of the long-chain omega-3 fatty
      acids is necessary for optimal cognitive performance. Taken together, the
      findings suggest that raising the currently low consumption among healthy adults
      may improve some aspects of cognitive performance. Nonetheless, evidence from
      randomized clinical trials is comparatively sparse and leaves unclear: (a)
      whether such effects are clinically significant, (b) whether effects of
      eicosapentaenoic acid and DHA differ, (c) which dimensions of cognitive function
      are affected, (d) the dose-response relationships, or (e) the time course of the
      response. Clarification of these issues through both laboratory and clinical
      investigations is a priority given the broad implications for public health, as
      well as for military personnel and other positions of high performance demand and
      responsibility. 

PMID- 25373095
TI  - The potential for military diets to reduce depression, suicide, and impulsive
      aggression: a review of current evidence for omega-3 and omega-6 fatty acids.
AB  - The current burden of psychological distress and illness poses as a significant
      barrier to optimal force efficacy. Here we assess nutrients in military diets,
      specifically highly unsaturated essential fatty acids, in the reduction of risk
      or treatment of psychiatric distress. Moderate to strong evidence from several
      meta-analyses of prospective cohort trials indicate that Mediterranean diet
      patterns reduce risk of clinical depressions. Specific nutrients and foods of
      biological interest in relation to mental health outcomes are then discussed and
      evaluated. Moderate evidence indicates that when fish consumption decreases and
      simultaneously omega-6 increases, the risk of clinical depressive symptoms are
      elevated. One meta-analysis examining tissue compositions provides moderate to
      strong evidence that higher levels of omega-3 highly unsaturated fatty acids
      (HUFAs) (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid)
      are associated with decreased risk of clinical depressions. Other meta-analytic
      reviews of randomized placebo-controlled trials provide moderate to strong
      evidence of significantly improving clinically depressive symptoms when the
      formulation given was >50% in eicosapentaenoic acid. Finally, a meta-analysis of
      omega-3 HUFAs provides modest evidence of clinical efficacy for attention-deficit
      hyperactivity disorder. This article recommends that a rebalancing of the
      essential fatty acid composition of U.S. military diets, achieve tissue
      compositions of HUFAs consistent with traditional Mediterranean diets, may help
      reduce military psychiatric distress and simultaneously increase force efficacy
      substantially. 

PMID- 25373097
TI  - The safety of fish oils for those whose risk of injury is high.
AB  - A diet rich in omega-3 polyunsaturated fatty acids (PUFAs) may decrease risk of
      cardiovascular disease by improving the blood lipid profile. The purpose of this
      review was to (1) determine if fish oil (omega-3) consumption increased the risk
      of hemorrhaging after a military injury and (2) whether an improvement in the
      omega-3 PUFA profile had an impact on survivability from military wounds. The
      authors found no evidence to contradict the existing U.S. Food and Drug
      Administration safety ruling that 3 g of omega-3 PUFA per day is generally
      regarded as safe. However, there is insufficient data with regard to the safety
      of consuming more than 3 g of omega-3 PUFA per day. More research is needed to
      safely recommend use of higher doses omega-3 PUFA. 

PMID- 25373096
TI  - Omega-3 fatty acids and stress-induced immune dysregulation: implications for
      wound healing.
AB  - Stress-related immune alterations can be consequential for health; they can
      enhance susceptibility to infectious agents and influence the severity of
      infectious disease, diminish the strength of immune responses to vaccines,
      reactivate latent viruses, and slow wound healing. Furthermore, stressful events
      and negative emotions promote systemic proinflammatory cytokine production while
      reducing beneficial local production of proinflammatory cytokines at the wound
      site that are important for wound healing. Dietary omega-3 and omega-6
      polyunsaturated fatty acids (PUFAs) also influence systemic inflammation; high
      proportions of omega-6 to omega-3 boost inflammation, while omega-3 has anti
      inflammatory properties. Additionally, the limited evidence thus far suggests
      that omega-3 PUFA may enhance local inflammatory responses at wound sites.
      Moreover, an individual's dietary proportion of omega-3 to omega-6 may influence
      the magnitude of inflammatory responses to stressful events. Thus, wound healing
      and surgery provide exemplars of how stress and depression can interact with the
      diet to influence important clinical outcomes. 

PMID- 25373098
TI  - Metabolic health benefits of long-chain omega-3 polyunsaturated fatty acids.
AB  - Restricting energy intake and increasing physical activity are advocated for
      reducing obesity, but many individuals have difficulty complying with these
      recommendations. Consumption of long-chain omega-3 polyunsaturated fatty acids (n
      3 LCPUFA) offers multiple mechanisms to counteract obesity, including appetite
      suppression; circulatory improvements, which promote nutrient delivery to
      skeletal muscle and changes in gene expression, which shift metabolism toward
      increased fat oxidation; increased energy expenditure; and reduced fat
      deposition. n-3 LCPUFA may also alter gene expression in skeletal muscle to
      suppress catabolic pathways and upregulate anabolic pathways, resulting in
      greater lean tissue mass, metabolic rate, and maintenance of physical function. n
      3 LCPUFA supplementation has been shown to counteract obesity in rodents, but
      evidence in humans is limited. Epidemiological associations between n-3 LCPUFA
      intakes and obesity are inconclusive. Several studies, on the other hand,
      indicate inverse relationships between biomarkers of n-3 LCPUFA status and
      obesity, although causality is uncertain. There have been few human intervention
      trials of omega-3 supplementation for obesity; some have indicated potential
      benefits, especially when combined with energy-restricted diets or exercise. More
      trials are needed to confirm these effects and identify mechanisms of action. 

PMID- 25373099
TI  - Omega-3 polyunsaturated fatty acids in the optimization of physical performance.
AB  - Increased oxidative stress and inflammatory responses among individuals
      performing strenuous exercise, elite athletes, or military personnel have been
      consistently reported. In addition, it is known that exhaustive and/or
      unaccustomed exercise can lead to muscle fatigue, delayed onset muscle soreness,
      and a decrement in performance. Omega-3 polyunsaturated fatty acids (omega3PUFAs)
      have been shown to decrease the production of inflammatory eicosanoids,
      cytokines, and reactive oxygen species, to possess immunomodulatory effects, and
      to attenuate inflammatory diseases. Although, a number of studies have assessed
      the efficacy of omega3PUFA supplementation on red blood cell deformability,
      muscle damage, inflammation, and metabolism during exercise, only a few studies
      have evaluated the impact of omega3PUFA supplementation on exercise performance.
      This review demonstrates that, at present, we cannot conclude the hypothesis that
      omega3PUFA supplementation is effective and ergogenic, and that the data is
      inconclusive whether omega3PUFA supplementation effectively attenuates the
      inflammatory and immunomodulatory response to exercise. Future human studies
      should assess the effectiveness of omega3PUFA supplementation on delayed onset
      muscle soreness, and subsequent exercise performance, in multisport athletes and
      military personnel who typically engage in more than one bout of exercise per day
      using a more robust research design than those that have been used in previous
      studies. 

PMID- 25373100
TI  - Considerations for incorporating eicosapentaenoic and docosahexaenoic omega-3
      fatty acids into the military food supply chain.
AB  - The U.S. military may consider exploring the inclusion of the long-chain omega-3
      fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the
      diets of active duty military personnel. To be successful, certain challenges
      must be overcome including determining appropriate dosage, ensuring cost
      efficiency, and optimizing stability. To increase EPA and DHA intake, the
      military should consider using one of three strategies, including mandates or
      recommendations on omega-3 supplement usage, contracts to purchase commercially
      available foods for distribution in the food supply chain, or direct addition of
      EPA and DHA into currently consumed foods. This review presents the challenges
      and strategies and provides potential suggestions to the military to increase the
      likelihood of success. 

PMID- 25373101
TI  - The challenges of incorporation of omega-3 fatty acids into ration components and
      their prevalence in garrison feeding.
AB  - Increasingly, private and military consumers are becoming aware of the positive
      benefits of a diet rich in omega-3 fatty acids (FAs) as health claims range from
      reducing inflammation to improving mood. The number of positive scientific
      articles supporting these claims is rapidly increasing, leading the military to
      examine the possibility of omega-3 supplementation for personnel. A variety of
      menus used either in shipboard or garrison feeding include fatty fishes that are
      rich in omega-3 FAs. However, omega-3 FAs have shelf-stability issues because of
      their susceptibility to oxidize; therefore, they create a challenge in terms of
      incorporation into ration components in nutritionally significant amounts. As a
      result, the Department of Defense Combat Feeding Directorate is investigating
      methods, technologies, and emerging products for incorporation of omega-3s into
      ration components. Based on existing research, fortification of foods with omega
      3 FAs would improve nutritional quality as well as provide added benefit to the
      Warfighters. 

PMID- 25373103
TI  - Omega-3 fatty acids: nutritional armor for the warfighter and historical trends
      behind optimal warrior performance.

PMID- 25373102
TI  - Understanding diet and modeling changes in the omega-3 and omega-6 fatty acid
      composition of U.S. garrison foods for active duty personnel.
AB  - Research indicates that dietary omega-3 and omega-6 polyunsaturated fatty acids
      (PUFAs) are important in reducing the risk of mental illness. We used the DoD
      Survey of Health Related Behaviors among Active Duty Military Personnel (HRBS) to
      assess current military dietary patterns and meal locations. We used the Lands
      Equation to model PUFAs in a sample Garrison diet and the nutritional impact of
      substitution of foods higher in omega-3 PUFAs and lower in omega-6 PUFAs on
      tissue composition. The military diet was very poor quality compared to 2010
      Healthy People Guidelines. A representative Garrison diet does not meet our
      estimated healthy n-3 HUFA intake at 3.5 g/d, corresponding with a tissue
      composition of 60% n-3 in HUFA (i.e., 40% n-6 in HUFA). Substitution of n-3 rich
      eggs, poultry, pork and other food commodities, combined with use on low linoleic
      acid oils, may contribute significantly to attaining healthier n-6/n-3
      proportions in the tissue. 

PMID- 25373104
TI  - Summary comments from workshop day 1: nutritional armor for the warfighter--can
      omega-3 fatty acids enhance stress resilience, wellness, and military
      performance?
AB  - The first day of this conference reviewed the literature on the intake of omega-3
      fatty acids, in all forms, around the world. Clinical trials using omega-3 fatty
      acids for a variety of pathological conditions, and studies examining omega-3
      supplementation in nonclinical populations, were examined. Finally, the basic
      science describing possible mechanisms for observed clinical effects was
      reviewed. Despite wide recognition that the minute levels needed to prevent
      clinical deficiency are probably not optimal for health, there is a dearth of
      information on intake needed to optimize performance among healthy populations.
      Randomized placebo-controlled trials in humans specially evaluating health
      outcomes relevant to military populations are needed. Widespread consensus must
      be built on solid evidence of appropriate intake, both in absolute terms and as a
      percentage of total fat, before a recommendation to change the intake of omega-3
      fatty acids in the Department of Defense is made. 

PMID- 25373105
TI  - Nutritional armor for the warfighter: can omega-3 fatty acids enhance stress
      resilience, wellness, and military performance?
AB  - This panel discussion, moderated by Dr. Deuster, illustrates the thinking of
      selected military leaders on the approach that must be taken to ensure the
      relationship between nutrition and performance. Insights and challenges these
      leaders face are provided, with consideration of the complex issues relating to
      sufficient scientific evidence, timing for Department of Defense policy, and the
      unique needs of service members. The discussion resulted in several
      recommendations. First, more nutritionists in uniform should be placed in/on the
      battlefield on every base and camp in Afghanistan and Iraq. Second,
      nutritionists/dietitians need to be working in the preventive arena, using the
      health promotion model and marketing to help shift behavior. Third, contract
      dietitians should be hired to work primarily in tertiary care. Dietitians must
      forward-deploy to implement preventive medicine and human performance
      optimization as it relates to nutrition and dietary supplementation.
      Unfortunately, almost all military dietitians are constrained within the medical
      model and we think of them just as "hospital providers." Finally, line units need
      to decide that dietitians are a requisite part of their force structure. Putting
      many dieticians in line units will allow our active duty members to believe diet
      and nutrition are important for performance. 

PMID- 25373106
TI  - The response of an expert panel to Nutritional armor for the warfighter: can
      omega-3 fatty acids enhance stress resilience, wellness, and military
      performance?
AB  - BACKGROUND: Recommendations of an Expert Panel on 5 central questions addressed
      during the workshop. METHODS: The Panel reviewed available scientific literature,
      workshop presentations, and comments from workshop guests. RESULTS: The Panel
      unanimously agreed that a military Daily Recommended Intake for long-chain omega
      3 fatty acids (FAs) should be established within the context of lowering current
      intakes of omega-6 FAs. The Panelists also felt that there was sufficient
      evidence to support increasing omega-3 intake to receive cardiovascular,
      immunological, and surgical benefits. In addition, research indicates that
      preloading with omega-3 FAs before combat exposure may be beneficial. Evidence
      for reduction of depressive symptoms and suicide prevention was felt to be
      strong. Insufficient data were available to evaluate post-traumatic stress
      disorder and impulsive aggression. Benefits for traumatic brain injury were
      promising. Adverse side effects were deemed negligible. CONCLUSION: The Panel
      concluded that based on studies analyzing omega-3 and omega-6 FA balance, it
      would be unethical to not attempt elevating the omega-3 status among U.S.
      military personnel.

PMID- 25373107
TI  - Control of robotic assistance using poststroke residual voluntary effort.
AB  - Poststroke hemiparesis limits the ability to reach, in part due to involuntary
      muscle co-activation (synergies). Robotic approaches are being developed for both
      therapeutic benefit and continuous assistance during activities of daily living.
      Robotic assistance may enable participants to exert less effort, thereby reducing
      expression of the abnormal co-activation patterns, which could allow participants
      to reach further. This study evaluated how well participants could perform a
      reaching task with robotic assistance that was either provided independent of
      effort in the vertical direction or in the sagittal plane in proportion to
      voluntary effort estimated from electromyograms (EMG) on the affected side.
      Participants who could not reach targets without assistance were enabled to reach
      further with assistance. Constant anti-gravity force assistance that was
      independent of voluntary effort did not reduce the quality of reach and enabled
      participants to exert less effort while maintaining different target locations.
      Force assistance that was proportional to voluntary effort on the affected side
      enabled participants to exert less effort and could be controlled to successfully
      reach targets, but participants had increased difficulty maintaining a stable
      position. These results suggest that residual effort on the affected side can
      produce an effective command signal for poststroke assistive devices. 

PMID- 25373108
TI  - Providing time-discrete gait information by wearable feedback apparatus for lower
      limb amputees: usability and functional validation.
AB  - Here we describe a novel wearable feedback apparatus for lower-limb amputees. The
      system is based on three modules: a pressure-sensitive insole for the measurement
      of the plantar pressure distribution under the prosthetic foot during gait, a
      computing unit for data processing and gait segmentation, and a set of vibrating
      elements placed on the thigh skin. The feedback strategy relies on the detection
      of specific gait-phase transitions of the amputated leg. Vibrating elements are
      activated in a time-discrete manner, simultaneously with the occurrence of the
      detected gait-phase transitions. Usability and effectiveness of the apparatus
      were successfully assessed through an experimental validation involving ten
      healthy volunteers. 

PMID- 25373109
TI  - Design and control of the MINDWALKER exoskeleton.
AB  - Powered exoskeletons can empower paraplegics to stand and walk. Actively
      controlled hip ab/adduction (HAA) is needed for weight shift and for lateral foot
      placement to support dynamic balance control and to counteract disturbances in
      the frontal plane. Here, we describe the design, control, and preliminary
      evaluation of a novel exoskeleton, MINDWALKER. Besides powered hip
      flexion/extension and knee flexion/extension, it also has powered HAA. Each of
      the powered joints has a series elastic actuator, which can deliver 100 Nm torque
      and 1 kW power. A finite-state machine based controller provides gait assistance
      in both the sagittal and frontal planes. State transitions, such as stepping, can
      be triggered by the displacement of the Center of Mass (CoM). A novel step-width
      adaptation algorithm was proposed to stabilize lateral balance. We tested this
      exoskeleton on both healthy subjects and paraplegics. Experimental results showed
      that all users could successfully trigger steps by CoM displacement. The step
      width adaptation algorithm could actively counteract disturbances, such as
      pushes. With the current implementations, stable walking without crutches has
      been achieved for healthy subjects but not yet for SCI paraplegics. More research
      and development is needed to improve the gait stability. 

PMID- 25373110
TI  - Influence of Heat Source, Thermal Radiation, and Inclined Magnetic Field on
      Peristaltic Flow of a Hyperbolic Tangent Nanofluid in a Tapered Asymmetric
      Channel.
AB  - In the present analytic thinking, we have modeled the governing equations of a
      two dimensional peristaltic transport of a Hyperbolic tangent nanofluid in the
      presence of a heat source/sink with the combined effects of thermal radiation and
      inclined magnetic field in a tapered asymmetric channel. The propagation of waves
      on the non-uniform walls to have different amplitudes and phase but the same wave
      speed is produced the tapered asymmetric channel. The equations of dimensionless
      temperature and nanoparticle concentration are solved analytically under
      assumptions of long wavelength and low Reynolds number. The governing equations
      of momentum of a hyperbolic tangent nanofluid for the tapered asymmetric channel
      have also been solved analytically using the regular perturbation method. The
      expression for average rise in pressure has been figured using numerical
      integrations. The effects of various physical parameters entering into the
      problem are discussed numerically and graphically. The phenomenon of trapping is
      also investigated. Furthermore, the received results show that the maximum
      pressure rise gets increased in case of non-Newtonian fluid when equated with
      Newtonian fluid.

PMID- 25373111
TI  - Modelling the Bioelectronic Interface in Engineered Tethered Membranes: From
      Biosensing to Electroporation.
AB  - This paper studies the construction and predictive models of three novel
      measurement platforms: (i) a Pore Formation Measurement Platform (PFMP) for
      detecting the presence of pore forming proteins and peptides, (ii) the Ion
      Channel Switch (ICS) biosensor for detecting the presence of analyte molecules in
      a fluid chamber, and (iii) an Electroporation Measurement Platform (EMP) that
      provides reliable measurements of the electroporation phenomenon. Common to all
      three measurement platforms is that they are comprised of an engineered tethered
      membrane that is formed via a rapid solvent exchange technique allowing the
      platform to have a lifetime of several months. The membrane is tethered to a gold
      electrode bioelectronic interface that includes an ionic reservoir separating the
      membrane and gold surface, allowing the membrane to mimic the physiological
      response of natural cell membranes. The electrical response of the PFMP, ICS, and
      EMP are predicted using continuum theories for electrodiffusive flow coupled with
      boundary conditions for modelling chemical reactions and electrical double layers
      present at the bioelectronic interface. Experimental measurements are used to
      validate the predictive accuracy of the dynamic models. These include using the
      PFMP for measuring the pore formation dynamics of the antimicrobial peptide PGLa
      and the protein toxin Staphylococcal alpha-Hemolysin; the ICS biosensor for
      measuring nano-molar concentrations of streptavidin, ferritin, thyroid
      stimulating hormone (TSH), and human chorionic gonadotropin (pregnancy hormone
      hCG); and the EMP for measuring electroporation of membranes with different
      tethering densities, and membrane compositions. 

PMID- 25373112
TI  - A Low-Power, Dual-Wavelength Photoplethysmogram (PPG) SoC With Static and Time
      Varying Interferer Removal.
AB  - This paper presents a low-power, reflectance-mode photoplethysmogram (PPG) front
      end with up to 100 MUA of static interferer current removal and 87 dB attenuation
      of time-varying interferers. The chip nominally consumes 425 MUW including signal
      chain circuits, red and IR LED drive power, clocks, digitization and I/O.
      Measured data shows the noise of the PPG signal to be dominated by the photodiode
      sensor photon shot noise. 

PMID- 25373113
TI  - Hyperparameter Selection for Gaussian Process One-Class Classification.
AB  - Gaussian processes (GPs) provide predicted outputs with a full conditional
      statistical description, which can be used to establish confidence intervals and
      to set hyperparameters. This characteristic provides GPs with competitive or
      better performance in various applications. However, the specificity of one-class
      classification (OCC) makes GPs unable to select suitable hyperparameters in their
      traditional way. This brief proposes to select hyperparameters for GP OCC using
      the prediction difference between edge and interior positive training samples.
      Experiments on 2-D artificial and University of California benchmark data sets
      verify the effectiveness of this method. 

PMID- 25373114
TI  - Suicide after release from prison: a population-based cohort study from Sweden.
AB  - OBJECTIVE: Released prisoners have high suicide rates compared with the general
      population, but little is known about risk factors and possible causal pathways.
      We conducted a population-based cohort study to investigate rates and risk
      factors for suicide in people previously imprisoned. METHOD: We identified
      individuals released from prison in Sweden between January 1, 2005, and December
      31, 2009, through linkage of national population-based registers. Released
      prisoners were followed from the day of release until death, emigration, new
      incarceration, or December 31, 2009. Survival analyses were conducted to compare
      incidence rates and psychiatric morbidity with nonconvicted population controls
      matched on gender and year of birth. RESULTS: We identified 38,995 releases among
      26,985 prisoners (7.6% female) during 2005-2009. Overall, 127 suicides occurred,
      accounting for 14% of all deaths after release (n = 920). The mean suicide rate
      was 204 per 100,000 person-years, yielding an incidence rate ratio of 18.2 (95%
      CI, 13.9-23.8) compared with general population controls. Previous substance use
      disorder (hazard ratio [HR] = 2.1; 95% CI, 1.4-3.2), suicide attempt (HR = 2.5;
      95% CI, 1.7-3.7), and being born in Sweden versus abroad (HR = 2.1; 95% CI, 1.2
      3.6) were independent risk factors for suicide after release. CONCLUSIONS:
      Released prisoners are at high suicide risk and have a slightly different pattern
      of psychiatric risk factors for suicide compared with the general population.
      Results suggest appropriate allocation of resources to facilitate transition to
      life outside prison and increased attention to prisoners with both a previous
      suicide attempt and substance use disorder.

PMID- 25373116
TI  - Perinatal psychiatry: an emerging specialty.

PMID- 25373115
TI  - Metabolic syndrome in a French cohort of patients with bipolar disorder: results
      from the FACE-BD cohort.
AB  - OBJECTIVE: The aim of this study was to estimate the prevalence of metabolic
      syndrome (MetS) and its components in a cohort of French patients with bipolar
      disorder; determine correlations with sociodemographic, clinical, and treatment
      related factors; and investigate the gap between optimal care and effective care
      of the treated patients. METHOD: 654 bipolar disorder patients from the FACE-BD
      cohort were included from 2009 to 2012. Sociodemographic and clinical
      characteristics, lifestyle information, and data on antipsychotic treatment and
      comorbidities were collected, and a blood sample was drawn. The Structured
      Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis
      of bipolar disorder. Metabolic syndrome was defined according to the National
      Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: 18.5%
      of individuals with bipolar disorder met criteria for MetS. Two-thirds of bipolar
      disorder patients did not receive adequate treatment for MetS components.
      Multivariate analysis showed that risk of MetS in men was nearly twice that in
      women (OR = 1.9; 95% CI, 1.0-3.8), and older patients had a 3.5 times higher risk
      (95% CI, 1.5-7.8) of developing MetS than patients under the age of 35 years.
      Moreover, patients receiving antipsychotic treatment had a 2.3 times increased
      risk (95% CI, 1.2-3.5) of having MetS, independent of other potential
      confounders. CONCLUSIONS: The prevalence of MetS is high in bipolar disorder
      patients, and there was considerable undertreatment of the components of MetS in
      this population. The prevention and treatment of cardiovascular diseases in these
      patients should be assessed systematically. The findings highlight the need for
      integrated care, with more interaction and coordination between psychiatrists and
      primary care providers.

PMID- 25373117
TI  - Impact of prenatal exposure to serotonin reuptake inhibitors or maternal major
      depressive disorder on infant developmental outcomes.
AB  - OBJECTIVE: To examine the impact of prenatal exposure to both serotonin reuptake
      inhibitors (SRIs; during any trimester) and maternal major depressive disorder
      (MDD; by DSM-IV criteria) on infant functioning. We hypothesized that infants
      with prenatal exposure to SRIs or MDD would have lower psychomotor, mental, and
      behavioral scores compared with nonexposed infants. METHOD: This longitudinal
      study included 166 mother-infant dyads: 68 with prenatal MDD/SRI (n = 41) or
      MDD/no SRI exposure (n = 27) and 98 nonexposed controls. Maternal depression and
      SRI exposure assessments were completed at or as near to 20, 30, and 36 prenatal
      weeks and 12, 26, 52, and 78 weeks postpartum as feasible. Infants were evaluated
      with the Bayley Scales of Infant Development, Second Edition, including the
      psychomotor (Psychomotor Development Index; PDI), cognitive (Mental Development
      Index; MDI), and behavioral (Behavioral Rating Scale; BRS) components. Study
      assessments occurred between 2003 and 2009. RESULTS: Neither prenatal exposure to
      MDD/SRI nor MDD/no SRI significantly impacted overall PDI, MDI, or BRS scores.
      However, we observed a significant SRI exposure by time interaction for the PDI
      (P = .038). MDD/SRI exposure was associated with lower PDI scores at 26 (mean =
      97.0) and 52 weeks (mean = 92.9) compared with nonexposed infants (mean = 101.4
      and 100.5). This difference was no longer significant at the 78-week assessment.
      CONCLUSIONS: Consistent with previous studies, we found no impact of prenatal
      MDD/SRI exposure on MDI scores. Less favorable PDI scores were observed in the
      first year; notably, these scores remained well within the normative range. The
      effects of prenatal MDD/SRI exposure on motor functioning may be transitory. A
      longitudinal pattern of poor developmental outcomes has not been established.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00279370.

PMID- 25373118
TI  - Clinical course of illness in women with early onset puerperal psychosis: a 12
      year follow-up study.
AB  - OBJECTIVE: To complete a follow-up analysis at a mean of 12 years after patients
      had presented with an early onset puerperal psychotic index episode. METHOD: A
      retrospective design was used. Patients with puerperal psychosis and onset within
      4 weeks after childbirth who had been referred to the Psychiatric Department of
      the Ludwig Maximilian University of Munich, Munich, Germany, between 1975 and
      1995 (maximum: 24 years, minimum: 7 years) were followed up after a mean of 12
      years post index episode. Ninety patients were included in the study. Before the
      index episode, 35 of the patients had previous nonpuerperal psychoses, while 55
      patients presented their index episode as the first manifestation of a psychotic
      illness. Diagnostic evaluation at follow-up was performed by the Structured
      Clinical Interview for DSM-IV Axis I Disorders according to DSM-IV-TR.
      Differential rates of risk of psychotic relapse were calculated. Data on some
      gynecologic variables (postpartum blues, premenstrual tension, psychiatric
      symptoms triggered perimenstrually, mood symptoms while taking oral
      contraceptives) were collected. Clinical and psychosocial outcomes were measured
      by the Global Assessment Scale and Disability Assessment Scale. RESULTS: Patients
      who presented with major depression and bipolar affective disorder with psychotic
      features at the initial index episode showed overall diagnostic stability. Many
      patients with initial brief psychosis (cycloid psychosis) shifted to a clear
      bipolar affective disorder. The general risk of a psychotic relapse was high
      (previous psychosis = 0.77 vs first psychotic manifestation = 0.56; not
      significant). The risk after further pregnancies was 0.57 versus 0.48,
      respectively (not significant), and the risk regarding at least 1 other psychotic
      nonindex episode was 0.71 versus 0.44, respectively (P = .015). Gynecologic
      variables did not significantly discriminate between the groups. In some
      patients, a possible link to a hormonal susceptibility was discussed. Patients
      who remained without any further psychotic relapse (n = 24) had a favorable
      outcome. CONCLUSIONS: Puerperal psychosis of an early onset seemed to be of a
      prevailing affective nature. Brief psychosis (cycloid psychosis) during a
      puerperal index episode showed a strong link to bipolar affective disorder in the
      further course of illness. Outcome was excellent in patients without a further
      psychotic relapse.

PMID- 25373119
TI  - A critical examination of studies on curcumin for depression.
AB  - Curcumin, an ingredient of turmeric, is widely available as a nutritional
      supplement. Curcumin has biological properties that suggest its use for a large
      number of health-related conditions, including depression. Curcumin is effective
      in animal models of depression. However, controlled clinical trials provide no
      convincing evidence that patients with major depressive illness fare better with
      different extracts of curcumin (dosed at 500-1,000 mg/d) than with placebo (or no
      treatment) after 5-8 weeks of monotherapy or antidepressant-augmentation therapy.
      At present, therefore, there is insufficient evidence to encourage depressed
      patients to consider curcumin as a possible alternative to standard
      antidepressant therapy. 

PMID- 25373120
TI  - Prophylactic antidepressant treatment of interferon-induced depression in chronic
      hepatitis C: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the utility of prophylactic administration of
      antidepressants in preventing a major depressive episode during antiviral
      treatment for chronic hepatitis C. DATA SOURCES: A computerized literature search
      was conducted in MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and
      ClinicalTrials.gov to locate articles published in any language from the earliest
      available online year until October 2012, using the following phrase and Boolean
      logic algorithm: "hepatitis and c and (interferon-alpha OR peginterferon OR
      (pegylated and interferon)) and (depression OR mood) and (prevention OR
      prophylactic OR prophylaxis OR antidepressant)." STUDY SELECTION: Double-blind,
      randomized, placebo-controlled trials using antidepressants prophylactically
      before starting antiviral therapy for chronic hepatitis C were included. At
      baseline, none of the patients in the trials presented depression (DSM-IV-TR
      criteria). Using keywords and cross-referenced bibliographies, 144 studies were
      identified and examined in depth. 137 articles were rejected because inclusion
      criteria were not met. Finally, 7 studies were included. DATA EXTRACTION: Data
      were extracted independently by 2 investigators. The primary outcome measure was
      the onset of a major depressive episode during the antiviral treatment.
      Depressive symptoms, other side effects, and sustained virologic response were
      also examined. A full review and meta-analysis were performed. Odds ratios (ORs),
      mean differences, and estimated numbers needed to treat (NNTs) with 95%
      confidence intervals (CIs) were calculated. RESULTS: 591 patients were randomly
      assigned to antiviral treatment and another intervention: escitalopram (n = 197),
      paroxetine (n = 42), citalopram (n = 53), or placebo (n = 299). Selective
      serotonin reuptake inhibitors (SSRIs), as a group, reduced the incidence of a
      major depressive episode during antiviral treatment (OR = 0.53; 95% CI, 0.33 to
      0.84). The NNT was 12 (95% CI, 7.0 to 37.9). SSRIs reduced depressive symptoms at
      24 weeks of treatment (mean difference -2.18; 95% CI, -4.25 to -0.10). With
      regard to side effects, only dizziness was associated with administration of
      antidepressants (OR = 2.65; 95% CI, 1.46 to 4.80). There were no differences in
      sustained virologic response (OR = 1.22; 95% CI, 0.58 to 2.57). CONCLUSIONS:
      Administration of SSRIs before starting antiviral treatment reduces the incidence
      of interferon-induced depression, with a relatively moderate prophylactic impact
      and good tolerability.

PMID- 25373121
TI  - Are selective serotonin reuptake inhibitors associated with hepatocellular
      carcinoma in patients with hepatitis C?
AB  - BACKGROUND AND AIMS: Selective serotonin reuptake inhibitors (SSRIs) are commonly
      prescribed for patients with chronic hepatitis C virus (HCV) infection. Research
      suggests that serotonin promotes the development and growth of hepatocellular
      carcinoma (HCC). We tested the hypothesis whether exposure to SSRIs is associated
      with an increased risk of HCC in HCV patients. METHOD: Patients who entered the
      United States Veterans Affairs (VA) Hepatitis C Clinical Case Registry in 2000 to
      2009 were analyzed. During the 8 years of follow-up, 36,192 patients filled at
      least 1 SSRI prescription. Cases of HCC were identified by diagnosis codes (ICD-9
      155.0). Multivariable Cox regression analyses estimated adjusted HCC hazard
      ratios (HRs) for SSRI-exposed versus SSRI-unexposed subjects and categories of
      average SSRI doses. RESULTS: The annual incidence of HCC in the VA registry
      cohort of 109,736 patients was 0.5% and significantly greater in the 8% with
      cirrhosis at baseline (HR = 5.2; 95% CI, 4.7-5.7). There was no evidence for
      significant interactions between the effect of SSRI-exposure and cirrhosis.
      Baseline characteristics of the exposed (n = 36,192) and unexposed (n = 73,544)
      subjects were similar. The median (interquartile range [IQR]) follow-up period
      after SSRI-exposure began was 44 (20-74) months with 18 (3-49) months between the
      first and last prescription. The median average SSRI dose during follow-up
      expressed as a fraction of initial recommended doses for depression was 0.94
      (IQR, 0.5 to 1.3). The risk of HCC was not significantly increased after SSRI
      exposure (HR = 0.96; 95% CI, 0.87-1.05) or with increasing SSRI doses.
      CONCLUSIONS: Analysis of a large cohort of HCV patients did not support the
      hypothesis that SSRIs increase the risk of developing HCC.

PMID- 25373122
TI  - Association of zolpidem use and subsequent increased risk of epilepsy: a
      population-based, case-control study.
AB  - OBJECTIVE: To evaluate the impact of long-term zolpidem use on the subsequent
      risk of epilepsy. METHOD: We used data from the National Health Insurance system
      of Taiwan to conduct a population-based case-control study. We identified 4,972
      newly diagnosed epilepsy patients (ICD-9-CM code 345) for the period of 2005-2010
      as cases. For each epilepsy case, 4 controls without a history of epilepsy were
      randomly selected from the rest of the population. Zolpidem was used as a
      predictor of epilepsy. RESULTS: Patients with epilepsy exhibited an adjusted odds
      ratio (OR) of 1.86 (95% CI, 1.70-2.03) and were, therefore, more strongly
      associated with zolpidem exposure than control patients were. The adjusted OR of
      epilepsy increased with the increase of mean zolpidem exposure (g/y). Compared
      with the OR of nonusers, the adjusted OR was 1.64 (95% CI, 1.44-1.86) for those
      who had taken < 1.0 g/y of zolpidem and 2.38 (95% CI, 2.06-2.74) for those who
      had taken >= 20.0 g/y of zolpidem. An adjusted OR of 3.55 (95% CI, 2.94-4.28) was
      noted to be associated with epilepsy when users had stopped taking the drug less
      than 7 days earlier. The estimated risk declined to an OR of 1.62 (95% CI, 1.47
      1.78) when users had stopped taking the drug more than 90 days earlier.
      CONCLUSIONS: This population-based, retrospective case-control study revealed a
      possible increase in epilepsy risk with zolpidem use, at either typical or
      supratherapeutic doses. These findings might stimulate public interest in safety
      issues regarding zolpidem use.

PMID- 25373123
TI  - Military sexual trauma in US veterans: results from the National Health and
      Resilience in Veterans Study.
AB  - OBJECTIVE: To evaluate the prevalence of military sexual trauma (MST) among US
      veterans, identify sociodemographic and military characteristics of MST, and
      examine the relationships between MST and psychiatric comorbidities,
      functioning/quality of life, and mental health treatment utilization. METHOD:
      Data were analyzed from the National Health and Resilience in Veterans Study, a
      contemporary, nationally representative survey of 1,484 US veterans conducted
      September-October 2013. Poststratification weights were applied to analyses to
      permit generalizability of results to the US veteran population. Outcomes
      measured include history of MST, trauma histories, lifetime and current DSM-IV
      mental disorders, functioning and quality of life, and utilization of mental
      health treatment. RESULTS: The overall prevalence of MST was 7.6% and was higher
      among female than male veterans (32.4% vs 4.8%) and younger than older veterans
      (22.8% among veterans aged 18-29 years vs 4.5% among veterans aged 60+ years).
      After adjustment for sociodemographic and military characteristics, MST was
      associated with elevated rates of current major depressive disorder,
      posttraumatic stress disorder, and generalized anxiety disorder (adjusted odds
      ratio [aOR] range, 2.19-3.12); past history of suicide attempt (aOR = 2.78) and
      current suicidal ideation (aOR = 2.19); and decreased mental and cognitive
      functioning and quality of life (Cohen d, 0.23-0.38). MST was also associated
      with increased current utilization of psychotropic medication (aOR = 3.70) and
      psychotherapy or counseling (aOR = 2.41), independent of psychiatric morbidities.
      CONCLUSIONS: 7.6% of US veterans screen positive for MST, with substantially
      higher rates among female and younger veterans. MST is associated with elevated
      rates of several psychiatric morbidities and suicidality, reduced functioning and
      quality of life, and increased mental health treatment utilization, independent
      of other sociodemographic, military, and mental health factors. These results
      suggest that MST is prevalent among US veterans and associated with elevated
      health burden. Findings can help inform efforts to identify at-risk veterans and
      characterize the concomitant health burden and needs associated with MST in this
      population.

PMID- 25373124
TI  - Metformin for weight loss and control in patients with mood disorder.

PMID- 25373125
TI  - Acute and long-term behavioral outcome of infants and children exposed in utero
      to either maternal depression or antidepressants: a review of the literature.
AB  - OBJECTIVE: The authors reviewed the published literature on the acute and long
      term neurobehavioral effects on infants and children of either in utero exposure
      to maternal depression or in utero exposure to antidepressants. DATA SOURCES: The
      PubMed electronic database was searched to locate 292 English-language studies
      from the first available year to October 2013 using the keywords pregnancy,
      antidepressants, depression, perinatal, and neurobehavioral. STUDY SELECTION: The
      authors reviewed only prospective studies that assessed the impact of maternal
      depression during pregnancy or maternal antidepressant treatment during pregnancy
      on (1) clearly defined short-term behavioral outcomes in infants (perinatal
      outcome) or (2) longer-term behavioral outcomes in infants and children
      (neurodevelopmental outcome). DATA EXTRACTION: Studies were included if they were
      prospective and assessed the impact of maternal depression or maternal
      antidepressant treatment during pregnancy on clearly measurable, objective short
      term and longer-term behavioral outcomes in infants and children. RESULTS:
      Untreated depression during pregnancy is associated with short-term neonatal
      effects, including increased distress after delivery, less than optimal
      orientation and motor activity, and disrupted sleep. Longer-term effects on
      neurobehavioral outcome have also been reported, including disruptive social
      behavior, depression, and changes in the period of sensitivity for language
      discrimination. Antidepressant exposure during pregnancy is associated with
      adverse short-term perinatal symptomatology, including effects on autonomic and
      motor activity, habituation, and sleep. Longer-term studies of neurobehavioral
      outcomes of in utero antidepressant exposure suggest potential effects on gross
      motor function and language development but not cognition. CONCLUSIONS: In utero
      exposure to either maternal depression or antidepressants carries risks to the
      developing fetus. Treatment decisions regarding whether and how to treat
      depression during pregnancy must be made on an individual basis, with careful
      consideration of the impact of these decisions on both mother and infant.

PMID- 25373126
TI  - Anxiety disorders during pregnancy: a systematic review.
AB  - OBJECTIVE: To systematically evaluate the literature on anxiety disorders during
      pregnancy. DATA SOURCES: MEDLINE, PsycINFO, and CINAHL were searched through
      October 2013 for original research studies published in English using
      combinations of the terms pregnancy, prenatal, or pregnancy outcomes; anxiety
      disorder; and generalized anxiety. Reference lists of included studies were hand
      searched and a PubMed search for in-process reports was conducted. STUDY
      SELECTION: Relevant studies of anxiety disorders during pregnancy as determined
      by diagnostic interview were included if they reported on prevalence; course,
      onset, and/or risk factors; maternal, obstetric, or fetal/child outcomes; and/or
      treatment trial results. DATA EXTRACTION: Two reviewers independently extracted
      relevant data and assessed methodological quality of each study. RESULTS: Fifty
      seven reports were included. Reports provided information on panic disorder (25
      reports), generalized anxiety disorder (17 reports), obsessive-compulsive
      disorder (OCD) (23 reports), agoraphobia (6 reports), specific phobia (10
      reports), social phobia (14 reports), posttraumatic stress disorder (14 reports),
      and any anxiety disorder (18 reports). Twenty reports provided information on
      prevalence, 16 on course, 10 on risk factors, and 22 on outcomes. Only 1
      treatment study was identified. High anxiety disorder prevalence in pregnancy was
      found; however, estimates vary considerably, and evidence is inconclusive as to
      whether prevalence among pregnant women differs from that of nonpregnant
      populations. Considerable variation in prenatal course of OCD and panic disorder
      was found. Substantial heterogeneity limits conclusions regarding risk factors or
      outcomes. CONCLUSIONS: Additional research of higher methodological quality is
      required to more accurately determine prevalence, understand course, identify
      risk factors and outcomes, and determine effective treatments for anxiety
      disorders in pregnancy.

PMID- 25373127
TI  - Innovation in the treatment of bipolar depression.

PMID- 25373128
TI  - When positive isn't positive: the hopes and disappointments of clinical trials.

PMID- 25373129
TI  - Revealing the importance of military sexual trauma and its consequences.

PMID- 25373130
TI  - A proposal to refine the definition of military sexual trauma for purposes of
      treatment and research.

PMID- 25373131
TI  - Pros and cons of approved therapies for bipolar depression and ongoing unmet
      needs.
AB  - Patients with bipolar disorder spend more time depressed than manic, but fewer
      clinical trials have been conducted investigating treatments for bipolar
      depression than for bipolar mania. Olanzapine-fluoxetine combination, quetiapine,
      and lurasidone are the only FDA-approved treatments for bipolar depression.
      Clinical trials of these drugs show similar efficacy but different side effect
      profiles. Clinicians, therefore, should consider possible adverse events and
      individual patient characteristics when selecting treatments. 

PMID- 25373132
TI  - Assessing disability in schizophrenia: tools and contributors.
AB  - Patients with schizophrenia experience disability in areas of everyday life, such
      as employment, relationships, and independence, even after they achieve symptom
      remission. Clinicians can assess patients' functional disability by using
      information from multiple sources (patient, family member, case worker),
      collecting objective information, and evaluating real-life skills and cognitive
      abilities with performance-based assessment tools, such as the MATRICS Consensus
      Cognitive Battery or the University of California, San Diego, Performance-Based
      Skills Assessment (UPSA). Factors that contribute to functional disability
      include cognitive impairments and negative symptoms, which appear to have
      different effects on domains of functioning and likely require separate treatment
      interventions. 

PMID- 25373133
TI  - Recognizing and overcoming potential barriers to oral medications for MS.
AB  - Three FDA-approved oral medications are available for the treatment of relapsing
      forms of multiple sclerosis: fingolimod, teriflunomide, and dimethyl fumarate.
      While injection and IV treatments have proven to be beneficial, these newer oral
      agents also offer positive outcomes for patients. Numerous barriers exist,
      though, for these oral agents, including the unknown long-term efficacy and
      safety and potential side effects. Despite possible side effects, oral agents
      provide convenience, ease of use, and the elimination of injection/IV
      administration-site pain. To ensure MS patients receive the most appropriate
      individualized care, clinicians should present all of the available treatment
      options to both newly diagnosed and established patients. 

PMID- 25373134
TI  - Securing While Sampling in Wireless Body Area Networks With Application to
      Electrocardiography.
AB  - Stringent resource constraints and broadcast transmission in wireless body area
      network raise serious security concerns when employed in biomedical applications.
      Protecting data transmission where any minor alteration is potentially harmful is
      of significant importance in healthcare. Traditional security methods based on
      public or private key infrastructure require considerable memory and
      computational resources, and present an implementation obstacle in compact sensor
      nodes. This paper proposes a lightweight encryption framework augmenting
      compressed sensing with wireless physical layer security. Augmenting compressed
      sensing to secure information is based on the use of the measurement matrix as an
      encryption key, and allows for incorporating security in addition to compression
      at the time of sampling an analog signal. The proposed approach eliminates the
      need for a separate encryption algorithm, as well as the predeployment of a key
      thereby conserving sensor node's limited resources. The proposed framework is
      evaluated using analysis, simulation, and experimentation applied to a wireless
      electrocardiogram setup consisting of a sensor node, an access point, and an
      eavesdropper performing a proximity attack. Results show that legitimate
      communication is reliable and secure given that the eavesdropper is located at a
      reasonable distance from the sensor node and the access point. 

PMID- 25373135
TI  - Cascade Chaotic System With Applications.
AB  - Chaotic maps are widely used in different applications. Motivated by the cascade
      structure in electronic circuits, this paper introduces a general chaotic
      framework called the cascade chaotic system (CCS). Using two 1-D chaotic maps as
      seed maps, CCS is able to generate a huge number of new chaotic maps. Examples
      and evaluations show the CCS's robustness. Compared with corresponding seed maps,
      newly generated chaotic maps are more unpredictable and have better chaotic
      performance, more parameters, and complex chaotic properties. To investigate
      applications of CCS, we introduce a pseudo-random number generator (PRNG) and a
      data encryption system using a chaotic map generated by CCS. Simulation and
      analysis demonstrate that the proposed PRNG has high quality of randomness and
      that the data encryption system is able to protect different types of data with a
      high-security level. 

PMID- 25373136
TI  - An Integrated Framework for Human-Robot Collaborative Manipulation.
AB  - This paper presents an integrated learning framework that enables humanoid robots
      to perform human-robot collaborative manipulation tasks. Specifically, a table
      lifting task performed jointly by a human and a humanoid robot is chosen for
      validation purpose. The proposed framework is split into two phases: 1) phase I
      learning to grasp the table and 2) phase II-learning to perform the manipulation
      task. An imitation learning approach is proposed for phase I. In phase II, the
      behavior of the robot is controlled by a combination of two types of controllers:
      1) reactive and 2) proactive. The reactive controller lets the robot take a
      reactive control action to make the table horizontal. The proactive controller
      lets the robot take proactive actions based on human motion prediction. A measure
      of confidence of the prediction is also generated by the motion predictor. This
      confidence measure determines the leader/follower behavior of the robot. Hence,
      the robot can autonomously switch between the behaviors during the task. Finally,
      the performance of the human-robot team carrying out the collaborative
      manipulation task is experimentally evaluated on a platform consisting of a Nao
      humanoid robot and a Vicon motion capture system. Results show that the proposed
      framework can enable the robot to carry out the collaborative manipulation task
      successfully. 

PMID- 25373137
TI  - An Efficient Chemical Reaction Optimization Algorithm for Multiobjective
      Optimization.
AB  - Recently, a new metaheuristic called chemical reaction optimization was proposed.
      This search algorithm, inspired by chemical reactions launched during collisions,
      inherits several features from other metaheuristics such as simulated annealing
      and particle swarm optimization. This fact has made it, nowadays, one of the most
      powerful search algorithms in solving mono-objective optimization problems. In
      this paper, we propose a multiobjective variant of chemical reaction
      optimization, called nondominated sorting chemical reaction optimization, in an
      attempt to exploit chemical reaction optimization features in tackling problems
      involving multiple conflicting criteria. Since our approach is based on
      nondominated sorting, one of the main contributions of this paper is the proposal
      of a new quasi-linear average time complexity quick nondominated sorting
      algorithm; thereby making our multiobjective algorithm efficient from a
      computational cost viewpoint. The experimental comparisons against several other
      multiobjective algorithms on a variety of benchmark problems involving various
      difficulties show the effectiveness and the efficiency of this multiobjective
      version in providing a well-converged and well-diversified approximation of the
      Pareto front. 

PMID- 25373138
TI  - Recurrence of monoclonal IgA lambda glomerulonephritis in kidney allograft
      associated with multiple myeloma.
AB  - Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)
      has been described as a new entity resembling immune-complex glomerulonephritis
      (GN). The recurrence of proliferative GN with monoclonal IgG in the renal
      allograft has been reported. However, recurrence of proliferative GN with
      monoclonal IgA after renal allograft is undefined. We previously reported a case
      of a 35-year-old woman with proliferative glomerulonephritis with monoclonal
      lambda (lambda) with mesangial and subendothelial paracrystalline deposits in the
      native kidney and initially undetectable circulating monoclonal protein or clone
      by bone marrow biopsy or flow cytometry. Despite immunosuppressive therapy, her
      renal disease progressed to end-stage of renal disease (ESRD) and the patient
      ultimately received a renal allograft. Transplantation was followed by recurrence
      of IgA-lambda PGNMID 4 months after renal transplantation and was associated the
      diagnosis of multiple myeloma. To the best of our knowledge recurrence of IgA
      PGNMID with paracrystalline deposits has not been previously reported. 

PMID- 25373140
TI  - Lansoprazole-induced acute lung and liver injury: a case report.
AB  - A 61-year old woman was admitted with increasing dyspnea and deranged liver
      function tests. A chest X-ray revealed small volume lungs with reticulo-nodular
      shadowing. High resolution computed tomography of the chest revealed interlobular
      septal thickening. The patient subsequently underwent an open lung biopsy and
      ultrasound-guided liver biopsy, which were consistent with a hypersensitivity
      pneumonitis and drug-induced liver injury respectively. The patient had
      previously been commenced on lansoprazole 10 days before the onset of symptoms;
      this had been stopped at diagnosis. High dose prednisolone was commenced, and the
      patient went on to make a full recovery. Hypersensitivity pneumonitis is a form
      of interstitial lung disease that is rarely associated with lansoprazole; this is
      the first report of it causing an idiosyncratic reaction affecting the lung and
      liver simultaneously. This case demonstrates the importance of obtaining a full
      drug history, as early identification of the offending agent will improve
      outcomes. 

PMID- 25373139
TI  - alpha1-A680T variant in GUCY1A3 as a candidate conferring protection from
      pulmonary hypertension among Kyrgyz highlanders.
AB  - BACKGROUND: Human variation in susceptibility to hypoxia-induced pulmonary
      hypertension is well recognized. High-altitude residents who do not develop
      pulmonary hypertension may host protective gene mutations. METHODS AND RESULTS:
      Exome sequencing was conducted on 24 unrelated Kyrgyz highlanders living 2400 to
      3800 m above sea level, 12 (10 men; mean age, 54 years) with an elevated mean
      pulmonary artery pressure (mean+/-SD, 38.7+/-2.7 mm Hg) and 12 (11 men; mean age,
      52 years) with a normal mean pulmonary artery pressure (19.2+/-0.6 mm Hg) to
      identify candidate genes that may influence the pulmonary vascular response to
      hypoxia. A total of 140 789 exomic variants were identified and 26 116 (18.5%)
      were classified as novel or rare. Thirty-three novel or rare potential pathogenic
      variants (frameshift, essential splice-site, and nonsynonymous) were found
      exclusively in either >=3 subjects with high-altitude pulmonary hypertension or
      >=3 highlanders with a normal mean pulmonary artery pressure. A novel missense
      mutation in GUCY1A3 in 3 subjects with a normal mean pulmonary artery pressure
      encodes an alpha1-A680T soluble guanylate cyclase (sGC) variant. Expression of
      the alpha1-A680T sGC variant in reporter cells resulted in higher cyclic
      guanosine monophosphate production compared with the wild-type enzyme and the
      purified alpha1-A680T sGC exhibited enhanced sensitivity to nitric oxide in
      vitro. CONCLUSIONS: The alpha1-A680T sGC variant may contribute to protection
      against high-altitude pulmonary hypertension and supports sGC as a
      pharmacological target for reducing pulmonary artery pressure in humans at
      altitude.

PMID- 25373141
TI  - Rosette-forming glioneuronal tumor with dissemination throughout the ventricular
      system: a case report.
AB  - A 33-year-old female was found to have a rosette-forming glioneuronal tumor
      (RGNT) occurring within the fourth ventricle with multifocal extension to the
      third and lateral ventricles. She presented with headaches, blurred vision,
      nausea, and intermittent dizziness. A brain magnetic resonance imaging (MRI) scan
      showed hydrocephalus and multifocal nodules throughout the ventricular system
      with the largest mass occupying the fourth ventricle. An endoscopic third
      ventriculostomy and biopsy were performed. Histological examination demonstrated
      a glioneuronal neoplasm with the characteristic features of RGNT. While the
      histopathological features of our case are well in accord with those reported in
      the literature, the multifocal intraventricular growth pattern has only been
      described twice before. Moreover, RGNT of the fourth ventricle with dissemination
      throughout the supratentorial ventricles has only been described once before.
      Long-term studies are required to assess the best treatment modalities and
      clinical behavior of this extremely rare disseminated RGNT entity. 

PMID- 25373142
TI  - Large transcription units unify copy number variants and common fragile sites
      arising under replication stress.
AB  - Copy number variants (CNVs) resulting from genomic deletions and duplications and
      common fragile sites (CFSs) seen as breaks on metaphase chromosomes are distinct
      forms of structural chromosome instability precipitated by replication
      inhibition. Although they share a common induction mechanism, it is not known how
      CNVs and CFSs are related or why some genomic loci are much more prone to their
      occurrence. Here we compare large sets of de novo CNVs and CFSs in several
      experimental cell systems to each other and to overlapping genomic features. We
      first show that CNV hotpots and CFSs occurred at the same human loci within a
      given cultured cell line. Bru-seq nascent RNA sequencing further demonstrated
      that although genomic regions with low CNV frequencies were enriched in
      transcribed genes, the CNV hotpots that matched CFSs specifically corresponded to
      the largest active transcription units in both human and mouse cells.
      Consistently, active transcription units >1 Mb were robust cell-type-specific
      predictors of induced CNV hotspots and CFS loci. Unlike most transcribed genes,
      these very large transcription units replicated late and organized deletion and
      duplication CNVs into their transcribed and flanking regions, respectively,
      supporting a role for transcription in replication-dependent lesion formation.
      These results indicate that active large transcription units drive extreme locus-
      and cell-type-specific genomic instability under replication stress, resulting in
      both CNVs and CFSs as different manifestations of perturbed replication dynamics.

PMID- 25373143
TI  - Profiling the RNA editomes of wild-type C. elegans and ADAR mutants.
AB  - RNA editing increases transcriptome diversity through post-transcriptional
      modifications of RNA. Adenosine deaminases that act on RNA (ADARs) catalyze the
      adenosine-to-inosine (A-to-I) conversion, the most common type of RNA editing in
      higher eukaryotes. Caenorhabditis elegans has two ADARs, ADR-1 and ADR-2, but
      their functions remain unclear. Here, we profiled the RNA editomes of C. elegans
      at different developmental stages of wild-type and ADAR mutants. We developed a
      new computational pipeline with a "bisulfite-seq-mapping-like" step and achieved
      a threefold increase in identification sensitivity. A total of 99.5% of the
      47,660 A-to-I editing sites were found in clusters. Of the 3080 editing clusters,
      65.7% overlapped with DNA transposons in noncoding regions and 73.7% could form
      hairpin structures. The numbers of editing sites and clusters were highest at the
      L1 and embryonic stages. The editing frequency of a cluster positively correlated
      with the number of editing sites within it. Intriguingly, for 80% of the clusters
      with 10 or more editing sites, almost all expressed transcripts were edited.
      Deletion of adr-1 reduced the editing frequency but not the number of editing
      clusters, whereas deletion of adr-2 nearly abolished RNA editing, indicating a
      modulating role of ADR-1 and an essential role of ADR-2 in A-to-I editing.
      Quantitative proteomics analysis showed that adr-2 mutant worms altered the
      abundance of proteins involved in aging and lifespan regulation. Consistent with
      this finding, we observed that worms lacking RNA editing were short-lived. Taken
      together, our results reveal a sophisticated landscape of RNA editing and
      distinct modes of action of different ADARs. 

PMID- 25373144
TI  - Single haplotype assembly of the human genome from a hydatidiform mole.
AB  - A complete reference assembly is essential for accurately interpreting individual
      genomes and associating variation with phenotypes. While the current human
      reference genome sequence is of very high quality, gaps and misassemblies remain
      due to biological and technical complexities. Large repetitive sequences and
      complex allelic diversity are the two main drivers of assembly error. Although
      increasing the length of sequence reads and library fragments can improve
      assembly, even the longest available reads do not resolve all regions. In order
      to overcome the issue of allelic diversity, we used genomic DNA from an
      essentially haploid hydatidiform mole, CHM1. We utilized several resources from
      this DNA including a set of end-sequenced and indexed BAC clones and 100*
      Illumina whole-genome shotgun (WGS) sequence coverage. We used the WGS sequence
      and the GRCh37 reference assembly to create an assembly of the CHM1 genome. We
      subsequently incorporated 382 finished BAC clone sequences to generate a draft
      assembly, CHM1_1.1 (NCBI AssemblyDB GCA_000306695.2). Analysis of gene,
      repetitive element, and segmental duplication content show this assembly to be of
      excellent quality and contiguity. However, comparison to assembly-independent
      resources, such as BAC clone end sequences and PacBio long reads, indicate
      misassembled regions. Most of these regions are enriched for structural variation
      and segmental duplication, and can be resolved in the future. This publicly
      available assembly will be integrated into the Genome Reference Consortium
      curation framework for further improvement, with the ultimate goal being a
      completely finished gap-free assembly.

PMID- 25373145
TI  - Megabase-scale deletion using CRISPR/Cas9 to generate a fully haploid human cell
      line.
AB  - Near-haploid human cell lines are instrumental for genetic screens and genome
      engineering as gene inactivation is greatly facilitated by the absence of a
      second gene copy. However, no completely haploid human cell line has been
      described, hampering the genetic accessibility of a subset of genes. The near
      haploid human cell line HAP1 contains a single copy of all chromosomes except for
      a heterozygous 30-megabase fragment of Chromosome 15. This large fragment
      encompasses 330 genes and is integrated on the long arm of Chromosome 19. Here,
      we employ a CRISPR/Cas9-based genome engineering strategy to excise this sizeable
      chromosomal fragment and to efficiently and reproducibly derive clones that
      retain their haploid state. Importantly, spectral karyotyping and single
      nucleotide polymorphism (SNP) genotyping revealed that engineered-HAPloid (eHAP)
      cells are fully haploid with no gross chromosomal aberrations induced by Cas9.
      Furthermore, whole-genome sequence and transcriptome analysis of the parental
      HAP1 and an eHAP cell line showed that transcriptional changes are limited to the
      excised Chromosome 15 fragment. Together, we demonstrate the feasibility of
      efficiently engineering megabase deletions with the CRISPR/Cas9 technology and
      report the first fully haploid human cell line. 

PMID- 25373146
TI  - Genome accessibility is widely preserved and locally modulated during mitosis.
AB  - Mitosis entails global alterations to chromosome structure and nuclear
      architecture, concomitant with transient silencing of transcription. How cells
      transmit transcriptional states through mitosis remains incompletely understood.
      While many nuclear factors dissociate from mitotic chromosomes, the observation
      that certain nuclear factors and chromatin features remain associated with
      individual loci during mitosis originated the hypothesis that such mitotically
      retained molecular signatures could provide transcriptional memory through
      mitosis. To understand the role of chromatin structure in mitotic memory, we
      performed the first genome-wide comparison of DNase I sensitivity of chromatin in
      mitosis and interphase, using a murine erythroblast model. Despite chromosome
      condensation during mitosis visible by microscopy, the landscape of chromatin
      accessibility at the macromolecular level is largely unaltered. However, mitotic
      chromatin accessibility is locally dynamic, with individual loci maintaining
      none, some, or all of their interphase accessibility. Mitotic reduction in
      accessibility occurs primarily within narrow, highly DNase hypersensitive sites
      that frequently coincide with transcription factor binding sites, whereas broader
      domains of moderate accessibility tend to be more stable. In mitosis, proximal
      promoters generally maintain their accessibility more strongly, whereas distal
      regulatory elements tend to lose accessibility. Large domains of DNA
      hypomethylation mark a subset of promoters that retain accessibility during
      mitosis and across many cell types in interphase. Erythroid transcription factor
      GATA1 exerts site-specific changes in interphase accessibility that are most
      pronounced at distal regulatory elements, but has little influence on mitotic
      accessibility. We conclude that features of open chromatin are remarkably stable
      through mitosis, but are modulated at the level of individual genes and
      regulatory elements. 

PMID- 25373148
TI  - Effect of honey solution and water acquisition on survival of starved solenopsis
      mealybug, Phenacoccus solenopsis.
AB  - The current study examined the effects of honey solution and water access on
      feeding behavior and survival of starving solenopsis mealybugs, Phenacoccus
      solenopsis Tinsley (Hemiptera: Pseudococcidae). The electrical penetration graph
      technique and an artificial membrane system were used to check whether P.
      solenopsis could imbibe free water or other liquid, such as the honey solution
      used here, in its natural environment. The recorded electrical penetration graph
      waveforms revealed that P. solenopsis could continuously imbibe water-honey
      solution for several hours, which indicated that honey solution and water
      acquisition could possibly occur when P. solenopsis had access to such liquids in
      its natural environment. Waveforms of water-honey solution feeding alternated
      between two distinct feeding phases in a regular pattern, which was assumed to
      reflect inherent habits of feeding attempts. The effects of honey solution and
      water acquisition on survival of P. solenopsis was also examined. Comparison
      between P. solenopsis in different treatments (starved, water feeding, honey
      solution feeding, and cotton plant feeding) suggested that 1) P. solenopsis could
      accept but did not favor feeding on water or the honey solution, and 2) this
      feeding could prolong its survival, but had no effect on body size. 

PMID- 25373147
TI  - Large-scale genomic sequencing of extraintestinal pathogenic Escherichia coli
      strains.
AB  - Large-scale bacterial genome sequencing efforts to date have provided limited
      information on the most prevalent category of disease: sporadically acquired
      infections caused by common pathogenic bacteria. Here, we performed whole-genome
      sequencing and de novo assembly of 312 blood- or urine-derived isolates of
      extraintestinal pathogenic (ExPEC) Escherichia coli, a common agent of sepsis and
      community-acquired urinary tract infections, obtained during the course of
      routine clinical care at a single institution. We find that ExPEC E. coli are
      highly genomically heterogeneous, consistent with pan-genome analyses
      encompassing the larger species. Investigation of differential virulence factor
      content and antibiotic resistance phenotypes reveals markedly different profiles
      among lineages and among strains infecting different body sites. We use high
      resolution molecular epidemiology to explore the dynamics of infections at the
      level of individual patients, including identification of possible person-to
      person transmission. Notably, a limited number of discrete lineages caused the
      majority of bloodstream infections, including one subclone (ST131-H30)
      responsible for 28% of bacteremic E. coli infections over a 3-yr period. We
      additionally use a microbial genome-wide-association study (GWAS) approach to
      identify individual genes responsible for antibiotic resistance, successfully
      recovering known genes but notably not identifying any novel factors. We
      anticipate that in the near future, whole-genome sequencing of microorganisms
      associated with clinical disease will become routine. Our study reveals what kind
      of information can be obtained from sequencing clinical isolates on a large
      scale, even well-characterized organisms such as E. coli, and provides insight
      into how this information might be utilized in a healthcare setting. 

PMID- 25373149
TI  - Selection and validation of reference genes for functional studies in the
      Calliphoridae family.
AB  - The genera Cochliomyia and Chrysomya contain both obligate and saprophagous
      flies, which allows the comparison of different feeding habits between closely
      related species. Among the different strategies for comparing these habits is the
      use of qPCR to investigate the expression levels of candidate genes involved in
      feeding behavior. To ensure an accurate measure of the levels of gene expression,
      it is necessary to normalize the amount of the target gene with the amount of a
      reference gene having a stable expression across the compared species. Since
      there is no universal gene that can be used as a reference in functional studies,
      candidate genes for qPCR data normalization were selected and validated in three
      Calliphoridae (Diptera) species, Cochliomyia hominivorax Coquerel, Cochliomyia
      macellaria Fabricius, and Chrysomya albiceps Wiedemann . The expression stability
      of six genes ( Actin, Gapdh, Rp49, Rps17, alpha -tubulin, and GstD1) was
      evaluated among species within the same life stage and between life stages within
      each species. The expression levels of Actin, Gapdh, and Rp49 were the most
      stable among the selected genes. These genes can be used as reliable reference
      genes for functional studies in Calliphoridae using similar experimental
      settings. 

PMID- 25373150
TI  - Evaluation of the influence of the antibiotic ciprofloxacin in the development of
      an Old World screwworm fly, Chrysomya putoria.
AB  - Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae), an Old World screwworm
      fly, is a species with potential for maggot therapy practice and has been
      described in myiasis and forensic entomology studies. The objective of the
      present study was to assess the action of different ciprofloxacin concentrations
      on the growth and development of C. putoria. First instar maggots of the third
      generation were raised on 60 g of chicken gizzard homogenate in 65% agar diet and
      received ciprofloxacin chloridrate. Each concentration of the antibiotic tested
      (3.33 ug/mL, 6.66 ug/mL, and 13.33 ug/mL) and the control (no antibiotic) were
      replicated four times (40 maggots/replication). The control received distilled
      water instead of the antibiotic. Maggots were kept in an acclimatized chamber at
      30 degrees  C during the day and 28 degrees  C at night, with 70 + 10% RH and a
      14:10 L:D photoperiod. They were weighed in batches of five and stored in test
      tubes sealed with nylon fabric and elastic. Microsoft Excel and STAT were used
      for the analysis. The variation among the maggot weight means and the duration of
      the maggot stage, pupal stage, and time to total development (neolarvae to adult)
      were analyzed by Student's t-test (alpha= 5%). The viabilities and the normality
      rates were compared using ANOVA, and the expected sex ratio frequency was tested
      by the chisquared test (chi(2)). There was no significant difference among the
      four treatments regarding mean individual maggot weight, mean duration of the
      maggot inoculation until abandonment, the duration of the maggot and pupal
      stages, and the total duration of all stages. The sex ratios found in the four
      treatments did not differ from the expected. Only treatment 2 (6.66 ug/mL
      concentration of ciprofloxacin) differed significantly from the control in maggot
      and total viability. The antibiotic did not seem to alter C. putoria development
      in the postembryonic period. 

PMID- 25373151
TI  - Evaluating buprestid preference and sampling efficiency of the digger wasp,
      Cerceris fumipennis, using morphometric predictors.
AB  - In-ground colonies of the native digger wasp, Cerceris fumipennis Say
      (Hymenoptera: Crabronidae), were sampled over two years in four New York State
      counties to characterize prey range, primarily their preying on beetles in the
      metallic wood-boring family, Buprestidae. These records were also used to
      evaluate beetle sampling efficiency by comparing collected beetles to historic
      county records and to identify limitations of wasp-mediated sampling in study
      areas. Overall, 1,530 beetles representing three families and 44 beetle species
      were collected from C. fumipennis. Five of these species (Agrilus cuprescens
      (Menetries) (Coleoptera: Buprestidae), A. pensus Horn, Buprestis nutalli Kirby,
      Chrysobothris scabripennis Gory and Laporte, Dicerca pugionata (Germar)) were new
      prey records for C. fumipennis. The wasps exhibited a strong preference for
      larger beetle genera (e.g., Dicerca, Buprestis), which accounted for 68% of
      beetles caught. Agrilus and Chrysobothris were the next dominant genera,
      accounting for 16% and 11%, respectively. A 4-19 mm prey size range is proposed,
      as all beetles collected were within this range despite the availability of prey
      outside of this range. Cerceris fumipennis caught 43% of the 42 buprestids
      species present in museum records from the four census counties as well as an
      additional 23 buprestid species that were not represented in museum records. Of
      the 22 buprestid species identified in museum collections that were not caught by
      C. fumipennis in the census counties, only one was within the proposed size range
      and active during the C. fumipennis flight season (late June through August).
      Overall, sampling C. fumipennis colonies over two summers at five sites resulted
      in 32% of the recorded buprestid species in New York State being caught,
      indicating that monitoring colonies is an efficient and viable means of
      quantifying buprestid assemblages.

PMID- 25373152
TI  - Impact of temperature on postdiapause and diapause of the Asian gypsy moth,
      Lymantria dispar asiatica.
AB  - Lymantria dispar asiatica (Vnukovskij) (Lepidoptera: Lymantridae) is one of three
      gypsy moth subspecies found in East Asia. Understanding the diapause and
      postdiapause phases of its eggs is important in characterizing its life cycle.
      The effects of different constant temperatures for different lengths of times on
      field-collected, postdiapause eggs were tested during the first year. In the
      second year, the effects of the same treatments on laboratory-raised eggs in
      diapause were investigated. The effects of temperature on percent egg hatching,
      time to hatching, and hatching duration were determined. When field-collected
      eggs were held at 0 and 5 degrees C, they terminated postdiapause within 11 days.
      The percent hatching tended to decline with an increased duration of exposure at
      temperatures greater than 5 degrees C. Diapause terminated slowly (> 37 days) and
      with a high percentage of hatching for postdiapause eggs held at 10 degrees C.
      There was a positive correlation between temperature and the speed of
      postdiapause development for field-collected eggs held at constant temperatures
      between 10 and 25 degrees C. However, the number of days to the first hatch was
      significantly longer than for eggs treated with lower temperatures before being
      transferred to 25 degrees C. Freshly oviposited eggs treated at a constant 0 or 5
      degrees C for 200 days were unable to develop into pharate larva. However, eggs
      treated at a constant 20 or 25 degrees C for 200 days developed into pharate
      larva but did not hatch even after a subsequent chill. This result suggests why
      L. dispar asiatica is not found in tropical areas and helps us to predict the
      distribution of the gypsy moth in China. 

PMID- 25373153
TI  - Wolbachia infection and Lepidoptera of conservation concern.
AB  - Conservation of at-risk species requires multi-faceted and carefully-considered
      management approaches to be successful. For arthropods, the presence of
      endosymbiotic bacteria, such as Wolbachia (Rickettsiales: Rickettsiaceae), may
      complicate management plans and exacerbate the challenges faced by conservation
      managers. Wolbachia poses a substantial and underappreciated threat to the
      conservation of arthropods because infection may induce a number of phenotypic
      effects, most of which are considered deleterious to the host population. In this
      study, the prevalence of Wolbachia infection in lepidopteran species of
      conservation concern was examined. Using standard molecular techniques, 22
      species of Lepidoptera were screened, of which 19 were infected with Wolbachia.
      This rate is comparable to that observed in insects as a whole. However, this is
      likely an underestimate because geographic sampling was not extensive and may not
      have included infected segments of the species' ranges. Wolbachia infections may
      be particularly problematic for conservation management plans that incorporate
      captive propagation or translocation. Inadvertent introduction of Wolbachia into
      uninfected populations or introduction of a new strain may put these populations
      at greater risk for extinction. Further sampling to investigate the geographic
      extent of Wolbachia infections within species of conservation concern and
      experiments designed to determine the nature of the infection phenotype(s) are
      necessary to manage the potential threat of infection. 

PMID- 25373154
TI  - Multiplex PCR in determination of Opiinae parasitoids of fruit flies, Bactrocera
      sp., infesting star fruit and guava.
AB  - Malaysia is a tropical country that produces commercial fruits, including star
      fruits, Averrhoa carambola L. (Oxalidales: Oxalidaceae), and guavas, Psidium
      guajava L. (Myrtales: Myrtaceae). There is a high demand for these fruits, and
      they are planted for both local consumption and export purposes. Unfortunately,
      there has been a gradual reduction of these fruits, which has been shown to be
      related to fruit fly infestation, especially from the Bactrocera species. Most
      parasitic wasps (Hymenoptera: Braconidae: Opiinae) are known as parasitoids of
      fruit fly larvae. In this study, star fruits and guavas infested by fruit fry
      larvae were collected from the Malaysian Agricultural Research and Development
      Institute. The parasitized larvae were reared under laboratory conditions until
      the emergence of adult parasitoids. Multiplex PCR was performed to determine the
      braconid species using two mitochondrial DNA markers, namely cytochrome oxidase
      subunit I and cytochrome b. Two benefits of using multiplex PCR are the targeted
      bands can be amplified simultaneously using the same reaction and the
      identification process of the braconid species can be done accurately and
      rapidly. The species of fruit flies were confirmed using the COI marker. The
      results obtained from our study show that Diachasmimorpha longicaudata (Ashmead)
      (Hymenoptera: Braconidae), Fopius arisanus (Sonan), and Pysttalia incisi
      (Silvestri) were parasitoids associated with Bactrocera carambolae (Drew and
      Hancock) (Diptera: Tephritidae) infested star fruits. Fopius arisanus was also
      the parasitoid associated with Bactrocera papayae (Drew and Hancock) infested
      guavas. Maximum parsimony was been constructed in Opiinae species to compare tree
      resolution between these two genes in differentiating among closely related
      species. The confirmation of the relationship between braconids and fruit fly
      species is very important, recognized as preliminary data, and highly necessary
      in biological control programs. 

PMID- 25373155
TI  - Sterile insect technique and F1 sterility in the European grapevine moth, Lobesia
      botrana.
AB  - Newly emerged adults of the European grapevine moth, Lobesia botrana (Denis and
      Schiffermuller) (Lepidoptera: Tortricidae), were irradiated with various doses of
      gamma radiation and crossed to unirradiated counterparts of the opposite sex.
      Fecundity was decreased when unirradiated females were mated with either 300-or
      350-Gy-irradiated males. Adult males that were irradiated with 400 Gy and mated
      with unirradiated females retained a residual fertility of 2.7%. The radiation
      dose at which irradiated females were found to be 100% sterile when mated with
      unirradiated males was 150 Gy. The inherited effects in the F1 progeny of
      irradiated male parents were examined at 100, 150, and 200 Gy. Fecundity and
      fertility of the F1 progeny of males irradiated with 150 Gy and inbred or crossed
      with irradiated and unirradiated moths were also recorded. A significant
      reduction in fertility was observed when F1 males mated with either F1 or
      unirradiated females. According to sterility index, F1 females who mated with F1
      males had greater sterility than when F1 females were crossed to 150-Gy
      irradiated males. Based upon the results of this study, 150 Gy of gamma radiation
      would be the optimal dose to use in a sterile insect technique and F1 sterility
      program against L. botrana. 

PMID- 25373156
TI  - The Dufour's gland and the cuticle in the social wasp Ropalidia marginata contain
      the same hydrocarbons in similar proportions.
AB  - Queens in many social insects are known to maintain their status through
      chemicals (pheromones) and cuticular hydrocarbons and have been the focus of many
      investigations that have looked at the chemicals involved in queen signaling. In
      the primitively eusocial wasp Ropalidia marginata Lepeletier (Hymenoptera:
      Vespidae), the Dufour's gland has been shown to be involved in queen signaling,
      and Dufour's gland hydrocarbons have been found to be correlated with fertility.
      Hence, this study analyzed the cuticle of R. marginata along with the Dufour's
      gland in order to compare their hydrocarbon profiles. The results show that the
      Dufour's gland and cuticle contained the same set of hydrocarbons in similar
      proportions (for the majority of compounds). Patterns pertaining to fertility
      signaling present in cuticular hydrocarbons were also similar to those present in
      the Dufour's gland hydrocarbons. Furthermore, the haemolymph contained the same
      hydrocarbons as found in the Dufour's gland and cuticle in similar proportions,
      thereby providing an explanation as to why the hydrocarbon profiles of the
      Dufour's gland and cuticle are correlated. 

PMID- 25373157
TI  - Spermatozoon ultrastructure of hangingflies, Bittacus strigosus and Bittacus
      stigmaterus.
AB  - In the present study, spermatozoon ultrastructure was documented in two species
      of hangingflies, Bittacus strigosus Hagen (Mecoptera: Bittacidae) and B.
      stigmaterus Say. Structures considered important to phylogenetic assessment that
      were observed in B. strigosus and B. stigmaterus included a short bilayered
      acrosome, elongated nucleus, tube-like glycocalyx, centriole adjunct material,
      accessory bodies, two mitochondrial derivatives, extra axonemal rods, globular
      units, and 9+2 arrangement of microtubules in the axoneme. Comparisons were made
      to Bittacus planus Cheng, which was previously examined by electron microscopy
      (Xie and Hua 2010). Similarities among the ultrastructural characteristics of the
      three Bittacus species support the monophyly of this genus. Displacement of a
      mitochondrial derivative by an accessory body was documented for the first time.
      This paper includes clarifications on differences between accessory bodies and
      extra axonemal rods, which are issues important to phylogenetic placement. 

PMID- 25373158
TI  - Morphological variation on isolated populations of Praocis (Praocis) spinolai.
AB  - In this study, the morphological variations of four geographically isolated
      populations of Praocis (Praocis) spinolai Gay & Solier (Coleoptera:
      Tenebrionidae) in the transitional coastal desert, Chile, were studied. The study
      was conducted in the coastal area of Punta de Choros and Los Choros-Archipelago,
      which includes three islands: Choros, Damas, and Gaviota. 113 specimens of the
      species P. (P.) spinolai belonging to the four locations sampled were collected
      analyzed with geometric morphometrics techniques to explore the pattern of shape
      variation on the different isolated environments. The principal component
      analysis revealed a well-defined pattern of variation between the populations
      analyzed. Moreover, differences between populations emerged also from the
      canonical variation analysis and were confirmed by the Procrustes ANOVA. All
      analyses performed confirmed the existence of a pattern of variation, due to the
      isolation of the populations and to environmental effects. The islands are
      subject to more arid pressures than the continent, where there is a more stable
      environment and the presence of coastal wetlands and the coastal range of
      mountains act together and enable fog condensation. This study indicates the
      existence of a clear pattern of variation, which indicates an evolutionary trend
      among the population examined. 

PMID- 25373159
TI  - The reproductive performance of the Mupli beetle, Luprops tristis, in relation to
      leaf age of the para rubber tree, Hevea brasiliensis.
AB  - An analysis of host plant leaf age preferences and phenology studies led to the
      predictions that tender rubber plant leaves are essential for the completion of
      the life cycle of the Mupli beetle, Luprops tristis Fabricius (Coleoptera:
      Tenebrionidae) and that low tender leaf availability during the post-dormancy
      stage will limit the beetle population. Analyses of the effects of feeding the
      beetles leaves of various ages, nitrogen (N) content, and moisture content on
      fecundity and the duration of post-dormancy survival were carried out. The
      results showed that tender leaf availability during the post-dormancy phase of L.
      tristis is a critical factor that determines the survival of L. tristis adults
      and the subsequent generation. The control of powdery mildew ( Odium hevea)
      disease-mediated premature leaf fall in rubber plantations may regulate the
      beetle population. A peak in fecundity during the early phase of post-dormancy is
      proposed as an adaptive mechanism of L. tristis to synchronize egg production and
      feeding with tender leaf availability in rubber plantations. Variations in
      nutrient levels and moisture content between deciduous rubber tree leaves of
      different ages are attributed to the leaf nutrient resorption mechanism of
      senescing leaves. These results established that tender leaves with high N and
      moisture levels are essential for post-dormancy survival and that N influences
      fecundity. The results of the experiments could aid decision making regarding the
      population management and control of L. tristis in rubber plantations. 

PMID- 25373160
TI  - The influence of natural and anthropic environmental variables on the structure
      and spatial distribution along longitudinal gradient of macroinvertebrate
      communities in southern Brazilian streams.
AB  - Southern Brazilian rivers and streams have been intensively affected by human
      activities, especially agriculture and the release of untreated domestic sewage.
      However, data about the aquatic macroinvertebrates in these streams are scarce
      and limited to only certain groups. In addition, studies focusing on the
      structure and spatial distribution of these communities are lacking. This study
      analyzed the effects of natural and anthropic variables on the community
      structure of macroinvertebrates along a longitudinal gradient in three
      microbasins located in a region of landscape transition in the state of Rio
      Grande do Sul, Brazil. Sampling was conducted in the Vacacai-Mirim River (August
      2008) and in the Ibicui-Mirim and Tororaipi rivers (August 2009) following an
      environmental gradient including 1(st), 2(nd), 3(rd), and 4(th) order segments.
      Local natural factors that were analyzed include water temperature, pH,
      electrical conductivity, dissolved oxygen, substrate granulometry, and the
      presence of aquatic vegetation. Anthropic variables that were analyzed include
      including bank erosion, land use, urbanization, riparian deforestation, and fine
      sediments input. A total of 42 families and 129 taxa were found, with
      predominance of environmentally tolerant taxa. Geological context (landscape
      transition and large hydrographic basins) tended to influence natural
      environmental factors along the rivers' longitudinal gradients. However, changes
      in anthropic variables were not affected by these geological differences and
      therefore did not correlate with patterns of spatial distribution in
      macroinvertebrate communities. Only 1(st) order stream segments showed a
      community composition with high richness of taxa intolerant to anthropic
      disturbance. Richness as a whole tended to be higher in 3(rd) to 4(th) order set
      of segments, but this trend was a result of local anthropic environmental
      disturbances. Future inventories conducted in similar landscape transition
      regions of Brazil, for conservation purposes, must consider stream segments of
      different orders, microbasins, and major basins in order to obtain data that
      faithfully reflect the regional diversity. Additionally, it is necessary to
      consider environmental gradients of land use and anthropic impacts in order to
      suggest appropriate strategies for conserving the environmental integrity of
      streams. 

PMID- 25373161
TI  - Nutritional and antinutritional composition of the five species of aquatic edible
      insects consumed in Manipur, India.
AB  - The people living in Manipur have a distinct identity, culture, and food habits.
      They have a prototype culture of eating insects. In our study, the nutritive
      contents of five potentially-edible aquatic insects, Lethocerus indicus
      (Lepeletier and Serville) (Hemiptera: Belostomatidae), Laccotrephes maculatus
      (F.) (Nepidae), Hydrophilus olivaceous (F.) (Coleoptera: Dytiscidae), Cybister
      tripunctatus (Olivier), and Crocothemis servilia (Drury) (Odonata: Libellulidae),
      were analyzed to inform consumers about the nutritional quality of the insects
      and the suggested quantity of their intake. A good amount of protein content and
      high gross energy was recorded among the insects. The results showed high levels
      of sodium, calcium, and magnesium present in the insects, indicating that they
      are a good source of minerals. Antinutritional properties of these insects were
      below 0.52%, which is a non-toxic level. Aquatic insects, such as C.
      tripunctatus, also possesses strong antioxidant activity (110 ug/mL). Therefore,
      these insects can play a major role in food security, health, and environment
      management. It is essential to cultivate edible insects to maintain their
      population sustainability. 

PMID- 25373162
TI  - Survey of Mymarommatidae and their occurrence in agricultural systems in Brazil.
AB  - Mymarommatidae surveys were carried out through the use of yellow pan traps in
      crops of green dwarf coconut, Cocos nucifera L. (Arecales: Arecaceae), papaya,
      Carica papaya L. (Brassicales: Caricaceae), citrus, Citrus spp. L. (Sapindales:
      Rutaceae), and guava, Psidium guajava L. (Myrtales: Myrtaceae), in the northern
      Espirito Santo State, Brazil. 146 specimens of mymarommatids were collected, of
      which 71, 55, 16, and 4 exemplars were obtained in the area cultivated with
      guava, papaya, citrus, and coconut, respectively. The mean numbers of
      mymarommatids collected in the period from April to June 2011 were significantly
      higher than those obtained in the other nine months. Two genera, Mymaromma and
      Mymaromella, were identified The most abundant genus was Mymaromma, comprising
      93.8% of the total collection; however, the genus Mymaromella was encountered in
      all crops. This is the first record of the presence of mymarommatids in these
      agricultural systems. 

PMID- 25373163
TI  - P element activity and molecular structure in Drosophila melanogaster populations
      from Firtina Valley, Turkey.
AB  - In order to study P element dynamics in natural populations of Drosophila
      melanogaster, 88 isofemale lines were examined from the Firtina Valley, Turkey.
      The P-M gonadal dysgenesis characteristics and the molecular patterns of P and KP
      elements were analyzed. Gonadal dysgenesis tests showed a slight variation both
      for P activity and P susceptibility, however the results showed a predominant M'
      phenotype for this region. The P and KP element were also characterized by
      polymerase chain reaction. The molecular analyses showed that all the populations
      examined had the entire 1.15 kb KP element. The molecular patterns of KP elements
      were the same for the populations studied. No clear relationship was found
      between phenotype and genomic P element composition. The correlations between the
      level of gonadal dysgenesis percentage (as an index for P activity and P
      susceptibility) and several geoclimatic factors were tested, and no general
      effects of altitude, temperature, rainfall, or humidity were found. The
      theoretical P' strain, which is very rare in natural populations, was also
      recorded for this region. 

PMID- 25373164
TI  - Effects of roads on Castanopsis carlesii seedlings and their leaf herbivory in a
      subtropical forest in China.
AB  - The effects of a forest road on Castanopsis carlesii (Hemsley) Hayata (Fagales:
      Fagaceae) seedlings and their leaf herbivory were investigated in a subtropical
      forest at Jiulianshan National Nature Reserve, Jiangxi, China. A total of 1124
      seedlings, 33949 leaves, 468 leaf mines, and 205 leaf galls were found.
      Generally, individual numbers, tree heights, and leaf numbers of C. carlesii
      seedlings became lower with increasing distances from the road. These results
      might indicate that old seedlings were fewer and survival rate of seedlings was
      lower in forest interiors. Leaf miners preferred the seedlings close to the
      forest road, while leaf gallers preferred the seedlings about 2 m from the road.
      Species diversity of leaf miners was higher in the forest interior area, while
      species diversity of leaf gallers was higher near the road. However, both leaf
      miners and leaf gallers decreased in general from the road to the interior
      forest. There were interspecific differences in the effects of roads on leaf
      miner species and leaf galler species. The effects of the road on seedlings and
      insects could be explained by varying microhabitat conditions and different
      ecological strategies. 

PMID- 25373165
TI  - Toxicological and biochemical characterizations of AChE in phosalone-susceptible
      and resistant populations of the common pistachio psyllid, Agonoscena pistaciae.
AB  - The toxicological and biochemical characteristics of acetylcholinesterases (AChE)
      in nine populations of the common pistachio psyllid, Agonoscena pistaciae
      Burckhardt and Lauterer (Hemiptera: Psyllidae), were investigated in Kerman
      Province, Iran. Nine A. pistaciae populations were collected from pistachio
      orchards, Pistacia vera L. (Sapindales: Anacardiaceae), located in Rafsanjan,
      Anar, Bam, Kerman, Shahrbabak, Herat, Sirjan, Pariz, and Paghaleh regions of
      Kerman province. The previous bioassay results showed these populations were
      susceptible or resistant to phosalone, and the Rafsanjan population was most
      resistant, with a resistance ratio of 11.3. The specific activity of AChE in the
      Rafsanjan population was significantly higher than in the susceptible population
      (Bam). The affinity (K(M)) and hydrolyzing efficiency (Vmax) of AChE on
      acetylthiocholine iodide, butyrylthiocholine iodide, and propionylthiocholine
      odide as artificial substrates were clearly lower in the Bam population than that
      in the Rafsanjan population. These results indicated that the AChE of the
      Rafsanjan population had lower affinity to these substrates than that of the
      susceptible population. The higher Vmax value in the Rafsanjan population
      compared to the susceptible population suggests a possible over expression of
      AChE in the Rafsanjan population. The in vitro inhibitory effect of several
      organophosphates and carbamates on AChE of the Rafsanjan and Bam populations was
      determined. Based on I50, the results showed that the ratios of AChE
      insensitivity of the resistant to susceptible populations were 23 and 21.7-fold
      to monocrotophos and phosphamidon, respectively. Whereas, the insensitivity
      ratios for Rafsanjan population were 0.86, 0.8, 0.78, 0.46, and 0.43 for
      carbaryl, eserine, propoxur, m-tolyl methyl carbamate, and carbofuran,
      respectively, suggesting negatively correlated sensitivity to organophosphate
      insensitive AChE. Therefore, AChE from the Rafsanjan population showed negatively
      correlated sensitivity, being insensitive to phosphamidon and monocrotophos and
      sensitive to N-methyl carbamates.

PMID- 25373166
TI  - A comparison of the life-history traits between diapause and direct development
      individuals in the cotton bollworm, Helicoverpa armigera.
AB  - In order to understand the differences of life-history traits between diapause
      and direct development individuals in the cotton bollworm, Helicoverpa armigera
      (Hubner) (Lepidoptera: Noctuidae), the development time, body size, growth rate,
      and adult longevity were investigated between the two populations, which were
      induced under 12:12 L:D and 16:8 L:D photoperiods, respectively, at 20, 22, and
      25 degrees C. The results indicated that the larval development time, pupal
      weight, adult weight, and growth rate were significantly different between
      diapause and direct developing individuals. The diapause developing individuals
      had a significantly higher pupal and adult weight and a longer larval time
      compared with direct developing individuals. However, the growth rate in diapause
      developing individuals was lower than that in the direct developing individuals.
      Analysis by GLM showed that larval time, pupal and adult weight, and growth rate
      were significantly influenced by both temperature and developmental pathway. The
      pupal and adult weights were greater in males than females in both developmental
      pathways, exhibiting sexual size dimorphism. The dimorphism in adult weight was
      more pronounced than in pupal weight because female pupae lost more weight at
      metamorphosis compared to male pupae. Protogyny was observed in both
      developmental pathways. However, the protogyny phenomenon was more pronounced at
      lower temperatures in direct developing individuals, whereas it was more
      pronounced in diapause developing individuals when they experienced higher
      temperatures in their larval stage and partial pupal period. The adult longevity
      of diapause developing individuals was significantly longer than that of direct
      developing individuals. The results reveal that the life-history strategy was
      different between diapause and direct developing individuals. 

PMID- 25373167
TI  - Comparative isoenzyme electrophoreses between the brown-spotted locust,
      Cyrtacanthacris tatarica, and the desert locust, Schistocerca gregaria.
AB  - The desert locust, Schistocerca gregaria (Forskal) (Orthoptera: Acrididae), and
      the brown-spotted locust, Cyrtacanthacris tatarica (Linne) (Orthoptera:
      Acrididae), were collected from Saudi Arabia to investigate their relationships.
      Native polyacrylamide gel electrophoreses of five arbitrarily chosen metabolic
      enzymes extracted from the leg muscles of the two locust taxa were conducted.
      These enzymes were acid phosphatase (Acph), alcohol dehydrogenase (Adh),
      betaester-ase (beta est), malic enzyme (Mal) and malate dehydrogenase (Mdh).
      Twenty presumptive gene loci and 26 polymorphic alleles were recorded. Acph did
      not discriminate between the two locust species, while the other four isoenzymes
      discriminated between them. Most of the alleles were monomeric, but Mal and Mdh
      exhibited dimeric alleles in the samples of C. tatarica. beta est fractions were
      more expressed in C. tatarica, and the three enzymes beta est, Mal, and Mdh
      discriminated clearly between the two species. The similarity coefficient that
      was calculated according to the number of sharing alleles between the two locusts
      was found to be 0.69. The isoenzyme variation presented herein seemed to reflect
      either their physiological adaptation or the taxonomic consequences between the
      two taxa. Collecting more isoenzymes for more samples could have taxonomic value.

PMID- 25373168
TI  - Polydomy in the ant Ectatomma opaciventre.
AB  - Tropical ants commonly exhibit a hyper-dispersed pattern of spatial distribution
      of nests. In polydomous species, nests may be satellites, that is, secondary
      structures of the main nest, where the queen is found. In order to evaluate
      whether the ant Ectatomma opaciventre Roger (Formicidae: Ectatomminae) uses the
      strategy of building polydomous nests, the spatial distribution pattern of 33
      nests in a 1,800 m(2) degraded area located in Rio Claro, SP, Brazil, were
      investigated using the nearest neighbor method. To complement the results of this
      investigation, the cuticular chemical profile of eight colonies was analyzed
      using Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS). The nests
      of E. opaciventre presented a hyper-dispersed or regular distribution, which is
      the most common in ants. The analysis of the cuticular hydrocarbons apparently
      con-firmed the hypothesis that this species is polydomous, since the chemical
      profiles of all studied colonies with nests at different sites were very similar
      to the chemical signature of the single found queen and were also different from
      those of colonies used as control.

PMID- 25373169
TI  - Keys to the species of Mydaeinae (Diptera: Muscidae) from China, with the
      description of four new species.
AB  - Four new species of Mydaeinae, Mydaea franzosternita n sp., Myospila
      apicaliciliola n sp., Myospila maoershanensis n sp., and Myospila subflavipennis
      n sp., are described and illustrated here for the first time. A key to the genus
      of Mydaeinae from China and keys to species of genera from Mydaeinae are
      provided.

PMID- 25373170
TI  - The fern-feeder aphids (Hemiptera: Aphididae) from China: a generic account,
      descriptions of one new genus, one new species, one new subspecies, and keys.
AB  - Fern-feeder aphids (Hemiptera: Aphididae) in China are represented by 13 species
      in 10 genera, including a new genus, Vietaphis gen nov., a new species, Vietaphis
      aliquantus sp nov., from Guizhou and Tibet on Plagiogyria japonicum, and a new
      subspecies, Amphorophora scabripes galba ssp nov., from Guizhou on Pentarhizidium
      intermedium. Two genera, Amphorophora Buckton and Idiopterus Davis, and four
      species or subspecies, Amphorophora ampullate ben-galensis Hille Ris Lambers and
      Basu, Idiopterus nephrelepidis Davis, Micromyzodium polypodii Takahashi, and
      Myzus filicis Basu, are reported for the first time in China. Apterae and alatae
      of Myzus filicis are redescribed herein, and with host plant notes. The fern
      feeder aphid genus Ne-omacromyzus Lee is considered a junior synonym of
      Idiopterus. Furthermore, Neomacromyzus cyrtomicola Lee is transferred to the
      genus Idiopterus, as Idiopterus cyrtomicola (Lee), comb nov., which is herein
      considered a junior synonym of Idiopterus nephrelepidis Davis. Keys to Chinese
      fern-feeder species are provided. Morphological figures and biometrical data of
      Vietaphis aliquantus sp nov., Amphorophora scabripes galba ssp nov., and Myzus
      filicis are presented.

PMID- 25373171
TI  - Serumfree culture of the suspension cell line QB-Tn9-4s of the cabbage looper,
      Trichoplusia ni, is highly productive for virus replication and recombinant
      protein expression.
AB  - Serumfree cultures of insect cells play an important role in the fields of
      protein engineering, medicine, and biology. In this paper, the suspension cell
      line QB-Tn9-4s of Trichoplusia ni (Hubner) (Lepidoptera: Noctuidae) was
      successfully adapted to serumfree Sf-900 III medium and passaged for 52
      generations. The adapted QB-Tn9-4s cells grew faster. Their population doubling
      time shortened from 27.4 hr in serum-containing medium to 24.1 hr, and their
      maximal density increased by 1.83-fold, reaching 3.50 *10(6) cells/mL in
      serumfree culture in T-flasks. The cells readily adapted to spinner culture, with
      maximum cell density of 4.40 * 10(6) cells/mL in a spinner flask. Although the
      infection rate of Autographa californica multiple nucleopolyhedrovirus and
      production of occlusion bodies (OBs) of the adapted QB-Tn9-4s cells were 91.0%
      and 85.4 OBs/cell, respectively, similar to those of QB-Tn9-4s cells cultured in
      serum-containing medium and control BTI-Tn5B1-4 cells, their budded virus titer
      was 4.97 *10(7) TCID50/mL, significantly higher than those of the latter two. In
      addition, the expression levels of beta-galactosidase at six days postinfection
      and secreted alkaline phosphatase at seven days postinfection in the adapted QB
      Tn9-4s cells reached 2.98 +/- 0.15*10(4) IU/mL and 3.34 +/- 0.13 IU/mL,
      respectively, significantly higher than those of QB-Tn9-4s and control BTI-Tn5B1
      4 cultured in serum-containing media. The above findings establish a foundation
      for industrial production of virus and recombinant proteins in QB-Tn9-4s
      serumfree culture.

PMID- 25373172
TI  - Quantification of supercolonial traits in the yellow crazy ant, Anoplolepis
      gracilipes.
AB  - Supercoloniality is a social structure displayed by many invasive ant species,
      but there has been surprisingly little research quantifying the extent to which
      individual species display traits underlying such social organisation. This study
      quantifies three traits for the yellow crazy ant, Anoplolepis gracilipes Smith
      (Hymenoptera: Formicidae): little or no aggression between workers from different
      nests; the exchange of workers among nests; and resource exchange among nests, as
      well as supercolony structure arising from patterns of distribution and density
      of detections. Supercolonies displayed a structural continuum from being small (
      < 10 ha) and "aggregated" with great continuity among detections through to being
      large (>10,000 ha) and "diffuse" with little continuity among detections. Smaller
      supercolonies had greater ant densities than larger supercolonies. In laboratory
      trials, no aggression was observed between workers from different nests sourced
      from different supercolonies, and paired nests merged within 24 hours. Workers
      lacked nest fidelity by rapidly populating artificial nests containing alien
      queens. The daily worker turnover rate per nest was estimated to be below 20%.
      Resources were readily moved among nests, with a resource being detected up to 13
      m away from a source within 24 hours, and as far as 32 m after four days. The
      rate and distance of resource movement increased with increasing worker and nest
      density. This research has demonstrated that A. gracilipes displays
      supercoloniality equivalent to that of the well-studied Argentine ant Linepithema
      humile. Quantification of these traits is required for other supercolonial
      species to improve our understanding of this social strategy, especially for
      invasive ants to aid in understanding factors that promote invasion success and
      to improve management. 

PMID- 25373173
TI  - Influence of host origin on host choice of the parasitoid Dinarmus basalis: does
      upbringing influence choices later in life?
AB  - The aim of this study was to investigate the influence of volatile compounds from
      four secondary host plants on the ability of Dinarmus basalis Rond. (Hymenoptera:
      Pteromalidae) to locate, recognize, and parasitize its host, 4(th)instar larvae
      or pupae of Callosobruchus maculatus F. (Coleoptera: Chrysomelidae). To examine
      this, strains of D. basalis were transferred from cow-pea seeds (Vigna
      unguiculata (L.) Walp. (Fabales: Fabaceae)) to pigeon pea (Cajanus cajan (L.)
      Millsp.) and two varieties of Bambara groundnut (Vigna subterranea (L.) Verdc.)
      seeds. The ability of D. basalis females to recognize the volatile compounds
      emanating from their complex host plant was tested by using a Y-tube olfactometer
      and a three-dimensional device. The results suggest that when females have a
      choice between pure air and the air emanating from their complex host of origin,
      they are attracted to the air tainted by the volatile compounds they have become
      accustomed to. They spent significantly more time (p < 0.0001) in the branch of
      the tube leading to the odorous air than in the tube leading to the pure air.
      When females from pigeon pea seed hosts were offered a choice between cowpea and
      pigeon pea seeds, all containing 4(th)instar larvae, the familiar odor of pigeon
      pea seeds were most attractive. When females from Bambara groundnut (white and
      striped) seed hosts were offered a choice between cowpea and pigeon pea seeds,
      all containing 4(th)instar larvae, they were significantly attracted to the odour
      of cowpea seeds. In the three-dimensional system, the females from the four
      strains did not appear to have any preference for a given type of seed containing
      4(th)instar larvae or pupae. The parasitism rate remained high on all four types
      of seeds used. These results show that the use of D. basalis as a biological
      control agent is possible in host changing situations where C. maculatus starts
      to attack other legumes. The results of this study also provide information
      supporting the behavioral plasticity of D. basalis. Understanding the mechanisms
      involved in the adaptive phenomena of biological control agents is discussed in
      the context of the development of adequate methods of pest control.

PMID- 25373174
TI  - Entomocidal effects of beech apricot, Labramia bojeri, seed extract on a soybean
      pest, the velvetbean moth, Anticarsia gemmatalis, and its enzymatic activity.
AB  - The effects of the beech apricot, Labramia bojeri A. de Candolle (Sapotales:
      Sapotaceae), seed aqueous extract on the larval development of the velvetbean
      moth, Anticarsia gemmatalis Hubner (Lepidoptera: Noctuidae), was evaluated. The
      extract inhibited larval development, pupal weight, and survival and emergence of
      adults. Digestive proteolytic activity in larval midgut and feces extracts was
      determined. Larvae fed 10 g/L of the aqueous extract showed a significant
      reduction in trypsin activity (~64%), when compared with control larvae. Trypsin
      and chymotrypsin activities were also detected in fecal material in aqueous
      extract-fed larvae, with about ~4.5 times more trypsin activity than the
      controls. The results from dietary utilization experiments with A. gemmatalis
      larvae showed a reduction in the efficiency of conversion of ingested food and
      digested food and an increase in approximate digestibility and metabolic cost.
      The effect of the extract suggests the potential use of L. bojeri seeds to
      inhibit the development of A. gemmatalis via oral exposure. The L. bojeri extract
      can be an alternative to other methods of control. 

PMID- 25373175
TI  - Molecular cloning and sequence analysis of novel cytochrome P450 cDNA fragments
      from Dastarcus helophoroides.
AB  - The predatory beetle Dastarcus helophoroides (Fairmaire) (Coleoptera:
      Bothrideridae) is a natural enemy of many longhorned beetles and is mainly
      distributed in both China and Japan. To date, no research on D. helophoroides
      P450 enzymes has been reported. In our study, for the better understanding of
      P450 enzymes in D. helophoroides, 100 novel cDNA fragments encoding cytochrome
      P450 were amplified from the total RNA of adult D. helophoroides abdomens using
      five pairs of degenerate primers designed according to the conserved amino acid
      sequences of the CYP6 family genes in insects through RT-PCR. The obtained
      nucleotide sequences were 250 bp, 270 bp, and 420 bp in length depending on
      different primers. Ninety-six fragments were determined to represent CYP6 genes,
      mainly from CYP6BK, CYP6BQ, and CYP6BR subfamilies, and four fragments were
      determined to represent CYP9 genes. Twenty-two fragments, submitted to GenBank,
      were selected for further homologous analysis, which revealed that some fragments
      of different sizes might be parts of the same P450 gene. 

PMID- 25373176
TI  - Insecticidal and antifeedant activities of clerodane diterpenoids isolated from
      the Indian bhant tree, Clerodendron infortunatum, against the cotton bollworm,
      Helicoverpa armigera.
AB  - The Indian bhant tree, Clerodendron infortunatum L. (Lamialus: Lamiaceae), is a
      well-known medicinal plant, but little information about its bioefficacy against
      agricultural pests exists. This scarcity was addressed in the present study, in
      which dried leaves of C. infortunatum were subjected to extraction with hexane
      and methanol and then partitioned using different solvents of varying polarity.
      In a preliminary bioassay, the antifeedant effects of the crude extracts and
      fractions were tested on a highly polyphagous pest, the cotton bollworm,
      Helicoverpa armigera Hubner (Lepidoptera: Noctuidae), using the no-choice test
      method with cabbage leaf discs. The methanol fraction resulted in maximum
      antifeedant activity. This fraction was further subjected to crystallization and
      column chromatography in order to isolate the compounds responsible for the
      activity. Three pure compounds were isolated and identified as clerodin (CL), 15
      methoxy-14, 15-dihydroclerodin (MD), and 15-hydroxy-14, 15-dihyroclerodin (HD).
      The antifeedant activity of these compounds was studied using a choice as well as
      a no-choice test method with 24 and 48 hr observation periods. Insecticidal
      activity was measured using the topical application method at 0.5, 1, 1.5, 2,
      2.5, and 3% concentrations, and data were recorded 24, 48, and 72 hr after
      treatment. In the no-choice test conditions, compounds CL and MD showed
      significantly higher antifeedant activity compared to the key ingredient in many
      commercial pesticides, azadirachtin, at its highest concentration. Compound HD
      also showed very good antifeedant activity, which did not differ significantly
      from that of azadirachtin. In the choice test conditions, all three compounds and
      azadirachtin showed 100% antifeedant activity at the highest concentration.
      Antifeedant Index (AI50) values of CL, MD, and HD were 6, 6, and 8 ppm in choice
      tests, and increased to 8, 9, and 11 ppm in the no-choice tests, respectively.
      Insecticidal activity of the isolated compounds was not significant compared to
      the control condition, even at the highest con-concentrations of the compounds.
      These results suggest that extracts of C. infortunatum have very good antifeedant
      effects against H. armigera due to the presence of specific compounds. These
      compounds could be utilized in the development of new biopesticides. 

PMID- 25373177
TI  - Acute, sublethal, and combination effects of azadirachtin and Bacillus
      thuringiensis on the cotton bollworm, Helicoverpa armigera.
AB  - The cotton bollworm, Helicoverpa armigera Hubner (Lepidoptera: Noctuidae) is a
      polyphagous and cosmopolitan insect pest that causes damage to various plants. In
      this study, the lethal and sublethal effects of azadirachtin and Bacillus
      thuringiensis Berliner sub sp . kurstaki (Bacillales: Bacillaceae) were evaluated
      on third instar H. armigera under laboratory conditions. The LC50 values of
      azadirachtin and Bt were 12.95 and 96.8 ug a.i./mL, respectively. A total
      mortality of 56.7% was caused on third instar larvae when LC20 values of the
      insecticides were applied in combination with each other. The LT50 values of
      azadirachtin and Bt were 4.8 and 3.6 days, respectively. The results of the
      sublethal study showed that the application of LC30 value of azadirachtin and Bt
      reduced the larval and pupal weight and increased larval and pupal duration of H.
      armigera. The longevity and fecundity of female adults were affected
      significantly by the insecticides. Female fecundity was reduced by the
      treatments, respectively. The lowest adult emergence ratio and pupation ratio
      were observed in the azadirachtin treatment. The results indicated that both
      insecticides have high potential for controlling of the pest. 

PMID- 25373178
TI  - Identification and analysis of the pigment composition and sources in the colored
      cocoon of the silkworm, Bombyx mori, by HPLC-DAD.
AB  - This study used the larval tissues and colored cocoons of silkworms, Bombyx mori
      L. (Lepidoptera: Bombycidae), that were fed leaves of cultivated mulberry, Husang
      32, as experimental material. The pigment composition and content in colored
      cocoons and tissues of the 5th instar larvae and the mulberry leaves were rapidly
      detected using organic solvent extraction and reverse phase high-performance
      liquid chromatography with diode array detection. It was found that the mulberry
      leaf mainly contained four types of pigment: lutein (30.86%), beta-carotene
      (26.3%), chlorophyll a (24.62%), and chlorophyll b (18.21%). The silk glands,
      blood, and cocoon shells of six yellow-red cocoons were used as the experimental
      materials. The results showed that there were generally two kinds of carotenoids
      (lutein and beta-carotene) in the silk gland and cocoon shell, a little
      violaxanthin was detected in silk gland, and the pigment found in the blood was
      mainly lutein in all varieties of silkworm tested. Chlorophyll a and b had not
      been digested and utilized in the yellow-red series of silkworm. The method used
      to detect visible pigments reported here could be used to breed new colors of
      cocoons and to develop and utilize the pigments found in mulberry. 

PMID- 25373179
TI  - Selection of Beauveria isolates pathogenic to adults of Nilaparvata lugens.
AB  - The brown planthopper, Nilaparvata lugens Stal (Hemiptera: Delphacidae), is a
      destructive invasive pest and has become one of the most economically-important
      rice pests in China. Effective control measures are desperately needed.
      Entomopathogenic fungi, such as Beauveria bassiana (Balsamo-Crivelli) Vuillemin
      (Hypocreales: Clavicipitaceae) and B. brongniartii (Saccardo), have shown great
      potential for the management of some sucking pest species. In this study, to
      explore alternative strategies for sustainable control of the sucking pest
      population, nine isolates of Beauveria from different pests were bioassayed under
      the concentrated standard spray of 1000 conidia/mm(2) in laboratory. The
      cumulative mortalities of adults ranged from 17.2 to 79.1% 10 days after
      inoculation. The virulence among all tested isolates exhibited significant
      differences (at p = 0.05). The highest virulent isolate was Bb09, which killed
      79.1% of the treated insects and had a median lethal time of 5.5 days. Its median
      lethal concentration values were estimated as 134 conidia/mm(2) on day 10. The
      chitinase activities of nine isolates were also assayed. The results showed that
      the chitinase activity (18.7 U/mg) of isolate Bbr09 was the highest among all
      tested isolates. The biological characteristics of these strains, including
      growth rate, sporulation, and germination rate, were further investigated. The
      results showed that strain Bbr09 exhibited the best biological characteristics
      with relatively higher hyphal growth rate, the highest spore production, and the
      fastest spore germination. The isolate of Bbr09 had strong pathogenicity and
      exhibited great potential for sustainable control of N. lugens.

PMID- 25373180
TI  - Molecular phylogenetic analysis of the Amiota taurusata species group within the
      Chinese species, with descriptions of two new species.
AB  - The relationships among six species of the Amiota taurusata Takada, Beppu, & Toda
      (Diptera: Drosophilidae) species group were investigated based on DNA sequence
      data of the mitochondrial NADH dehydrogenase subunit 2 ( ND2) gene, using three
      species of the genus Amiota as outgroups. A mitochondrial gene, cytochrome c
      oxidase I ( COI), can be used to discriminate between species of the taurusata
      group. Two new species are described from South China: A. protuberantis Shao et
      Chen, sp. nov. and A. shennongi Shao et Chen, sp. nov. A key to all the species
      of the taurusata group based on morphological characters is provided.

PMID- 25373181
TI  - Life table and consumption capacity of corn earworm, Helicoverpa armigera, fed
      asparagus, Asparagus officinalis.
AB  - The life table and consumption rate of Helicoverpa armigera (Hubner)
      (Lepidoptera: Noctuidae) reared on asparagus, Asparagus officinalis L.
      (Asparagales: Asparagaceae) were studied under laboratory conditions to assess
      their interaction. Development, survival, fecundity, and consumption data were
      analyzed by the age-stage, twosex life table. This study indicated that asparagus
      is a natural host of H. armigera. However, the poor nutritional content in
      asparagus foliage and the poor fitness of H. armigera that fed on asparagus
      indicated that asparagus is a suboptimal host in comparison to hybrid sweet corn.
      The uncertainty associated with life table parameters was estimated by using
      jackknife and bootstrap techniques, and the results were compared for statistical
      inference. The intrinsic rate of increase (r), finite rate of increase (lambda),
      net reproductive rate (R0), and mean generation time (T) were estimated by the
      jackknife technique to be 0.0780 day(-1), 1.0811 day(-1), 67.4 offspring, and
      54.8 days, respectively, while those estimated by the bootstrap technique were
      0.0752 day(-1), 1.0781 day(-1), 68.0 offspring, and 55.3 days, respectively. The
      net consumption rate of H. armigera, as estimated by the jackknife and bootstrap
      technique, was 1183.02 and 1132.9 mg per individual, respectively. The frequency
      distribution of sample means obtained by the jackknife technique failed the
      normality test, while the bootstrap results fit the normal distribution well. By
      contrast, the relationship between the mean fecundity and the net reproductive
      rate, as estimated by the bootstrap technique, was slightly inconsistent with the
      relationship found by mathematical proof. The application of the jackknife and
      bootstrap techniques in estimating population parameters requires further
      examination.

PMID- 25373182
TI  - Evaluation of three neonicotinoid insecticides against the common pistachio
      psylla, Agonoscena pistaciae, and its natural enemies.
AB  - The common pistachio psylla, Agonoscena pistaciae Burckhardt and Lauterer
      (Hemiptera: Psyllidae), is a key pest in pistachio orchards in Iran. Chemical
      control is a common method to manage this pest. Compatibility between natural
      enemies and pesticides is a primary concern in programs of integrated pest
      management of the psyllid pest. In this research, susceptibility of fifth instar
      nymphs of Ag. pistaciae and fourth instar larvae of the two most common predators
      of this pest, Adalia bipunctata L. (Coleoptera: Coccinellidae) and Coccinella
      undecimpunctata aegyptiaca Reiche, to acetamiprid, thiamethoxam, and imidacloprid
      was investigated. Probit analysis of concentration-mortality data was conducted
      to estimate the LC50 value. The results showed that thiamethoxam with an LC50
      value of 56.35 mg a.i./L was more toxic to fifth instar nymphs of Ag. pistaciae
      in comparison to acetamiprid (60.75 mg a.i/L) and imidacloprid (138.21 mg a.i/L)
      . Imidacloprid with an LC50 value of 218.89 mg a.i/L compared to acetamiprid
      (222.65 mg a.i/L) and thiamethoxam (232.37 mg a.i/L) had more lethal effects on
      fourth instar larvae of Ad. bipunctata. However, on the fourth instar larvae of
      C. undecimpunctata aegyptica, acetamiprid with an LC50 value of 263.44 mg a.i/L
      was more toxic than thiamethoxam (296.62 mg a.i/L) and imidacloprid (447.82 mg
      a.i/L). The laboratory findings showed that the three tested insecticides were
      more toxic to the common pistachio psylla than to its natural predators.
      Thiamethoxam was the most toxic against Ag. pistaciae. However, its toxicity to
      the predators was lower than imidacloprid and acetamiprid. This result suggests
      that thiamethoxam is the best insecticide for control of Ag. pistaciae in
      combination with predatory lady beetles. 

PMID- 25373183
TI  - Structure and properties of silk from the African wild silkmoth Gonometa postica
      reared indoors.
AB  - African wild silkmoth, Gonometa postica Walker (Lepidoptera: Lasiocampidae), were
      reared indoors in order to examine the influence of rearing conditions on the
      structure and properties of silk cocoon shells and degummed fibers by using a
      scanning electron microscope, an Instron tensile tester, and a thermogravimetric
      analyzer. The cocoons reared indoors showed inferior quality in weight, length,
      width, and cocoon shell ratio compared to cocoons reared outdoors. There were no
      differences in cocoon shell and fiber surfaces and cross sectional structures.
      Cocoon shells were covered with calcium oxalate crystals with few visible fibers
      on their surface. Degummed fibers were smooth with minimum unfractured surfaces
      and globular to triangular cross sections. Indoor-reared cocoon shells had a
      significantly higher breaking strain, while the breaking stress was higher for
      cocoons reared outdoors. Fibers from indoor cocoons had a significantly higher
      breaking stress while outdoor fibers had higher breaking strain.
      Thermogravimetric analysis curves showed two main thermal reactions revealing the
      dehydration of water molecules and ir-reversible decomposition of the
      crystallites in both cocoons and fibers reared indoors and outdoors. Cocoon
      shells underwent additional peaks of decomposition with increased temperature.
      The total weight loss was higher for cocoon shells and degummed fibers from
      indoors. Rearing conditions (temperature and relative humidity), feeding method
      used, changes in total life span, days to molting, and spinning might have
      influenced the variation in the properties observed.The ecological and commercial
      significances of indoor rearing of G. posticaare discussed. 

PMID- 25373184
TI  - The shoot-feeding ecology of three Tomicus species in Yunnan Province,
      southwestern China.
AB  - Three Tomicus pine shoot beetles, T. yunnanensis (Kirkendall and Faccoli)
      (Coleoptera: Scolytidae), T. minor (Hartig), and T. brevipilosus (Wood and
      Bright), have been causing serious damage to Yunnan pine ( Pinus yunnanensis
      (Franchet) (Pinales: Pinaceae)) stands in Yunnan, southwestern China. However,
      their ability to coexist in the crowns of the same trees during the shoot-feeding
      phase has not been elucidated. In our study, we investigated and compared the
      shoot-feeding ecology of the three species of pine shoot beetle in P. yunnanensis
      in Anning County, Yunnan Province. Shoot-feeding by T. yunnanensis, T. minor, and
      T. brevipilosus initiated in April, May, and June, and ended in February, April,
      and May, respectively. Individual T. yunnanensis and T. minor adults fed in
      shoots for about seven months, and T. brevipilosus for nine months, before
      initiating reproduction. All three Tomicus species fed in the current-year shoots
      close to the apical bud. No specific overwintering behavior was observed prior to
      reproduction. The entrance hole of T. yunnanensis was furthest away from the
      apical bud, and T. minor was the closest to the apical bud. Differences in the
      spatial distribution of these shoot-feeding sites might reduce competition among
      the three beetle species. The long-lasting and overlapping shoot-feeding by the
      three Tomicus species may reduce the resistance of P. yunnanensis and facilitate
      the reproduction of these beetles in the trunks of living trees, and thus help
      explain the severe damage by Tomicus in P. yunnanensis. 

PMID- 25373185
TI  - Natural history and morphology of the hoverfly Pseudomicrodon biluminiferus and
      its parasitic relationship with ants nesting in bromeliads.
AB  - The syrphid subfamily Microdontinae is characterized by myrmecophily of their
      immature stages, i.e., they develop in ant nests. Data on natural history of
      microdontines are scarce, especially in the Neotropics. Based on fieldwork in
      southern Brazil, this study provided new data on development and ecology of the
      hoverfly Pseudomicrodon biluminiferus (Hull) (Diptera: Syrphidae) as well as the
      first morphological descriptions of male genitalia, larvae, and pupa. Immature
      specimens were specifically found in colonies of the ant species Crematogaster
      limata Smith (Hymenoptera: Formicidae) found in rosettes of the bromeliad species
      Aechmea lindenii (E. Morren) Baker (Poales: Bromeliaceae) and A. nudicaulis (L.)
      Grisebach. Third instar larvae were observed preying on ant larvae, revealing the
      parasitic nature of P. biluminiferus. In this and several other aspects, the
      natural history of P. biluminiferus is similar to that of Holarctic microdontine
      species. Exceptions include: (i) indications that adults of P. biluminiferus
      outlast the winter months (in contrast to 3(rd)instar larvae in Holarctic
      species) and (ii) P. biluminiferus' relationship with bromeliads. The importance
      of bromeliads for this host-parasite system is evaluated in this paper. The
      single occurrence of another, unidentified microdontine species' pupae in a nest
      of the ant species Camponotus melanoticus Emery (Hymenoptera: Formicidae) is
      reported. 

PMID- 25373186
TI  - Shelter-building behavior and natural history of two pyralid caterpillars feeding
      on Piper stipulaceum.
AB  - Shelter-building behavior by caterpillars provides a mechanism of defense against
      predators, microenvironment enhancement, and in some cases nutritional benefits.
      This study provides a detailed description of the life cycle and shelter-building
      process of caterpillars, and identifies constraints and factors influencing this
      adaptive behavior in Lepidomys n. sp. near proclea Druce (Pyralidae:
      Chrysauginae), a tropical dry forest pyralid. Five macroscopic larval instars
      were detected during the life cycle, and activities performed during shelter
      building were categorized and timed. Caterpillar predators were identified, and
      20% of all collected larvae died due to attack by parasitoid wasps. Shelter
      building behavior was found to be constrained by the ontogenetic stage of
      caterpillars and influenced by leaf size of the host plant, Piper stipulaceum
      Opiz (Piperales: Piperaceae) . A similar pattern of shelter-building behavior
      exhibited by Tosale n. sp. near cuprealis larvae that coexisted in the same host
      plant is also described. Larvae of the second species were significantly less
      abundant than those of Lepidomys and hatched one month later in the rainy season,
      which could indicate some competitive interactions between these two pyralid
      species. 

PMID- 25373187
TI  - Variation between Ethiopian and North American barley varieties (Hordeum vulgare)
      in response to Russian wheat aphid (Diuraphis noxia) populations.
AB  - The Russian wheat aphid, Diuraphis noxia (Mordvilko) (Hemiptera: Aphididae),
      causes severe damage to barley, Hordeum vulgare L. (Poales: Poaceae), in the
      highlands of Ethiopia. Little information is available on the control of this
      pest in Ethiopia. An experiment aimed at evaluating the resistance of barley
      varieties from the USA to D. noxia populations and determining biotypic variation
      between Ethiopian and North American D. noxia populations was conducted. The D.
      noxia-resistant barley varieties Burton and RWA-1758 from the USA, the resistant
      barley line 3296-15 from Ethiopia, and a local Ethiopian susceptible variety were
      included in a randomized design in a greenhouse under natural light conditions.
      There were highly significant differences (P < 0.001) in the mean D. noxia
      population, leaf chlorosis, leaf rolling, plant stunting, number of tillers per
      plant, and the percentage of infested tillers per plant between the resistant and
      susceptible varieties. The aphid population per tiller was lower on the resistant
      barley plants than on the susceptible plants. Severe plant damage was observed on
      the local barley variety, while the least damage was observed on Burton, followed
      by RWA-1758. Burton and RWA-1758 were therefore highly resistant and moderately
      resistant, respectively, to the northern Ethiopian D. noxia populations,
      indicating similarities in biotypes between the United States and northern
      Ethiopian D. noxia populations. The damage to variety 3296-15 was greater than to
      Burton and RWA-1758. Leaf chlorosis scores and leaf rolling scores for variety
      3296-15 upon treatment with the north Ethiopian D. noxia population indicate
      likely biotypic variation between D. noxia populations of northern and central
      Ethiopia.

PMID- 25373188
TI  - Alternating temperatures affect the performance of Trichogramma species.
AB  - The environmental compatibility of a biological control agent is an important
      aspect of successful reduction of agricultural pests. Temperature fluctuations
      during the day have a strong influence on the performance of laboratory-reared
      parasitoids. In field conditions, Trichogramma (Hymenoptera: Trichogrammatidae)
      wasps are exposed to variable temperatures during their development, which has a
      significant impact on their ability to control pest species. A simulation-based
      study was undertaken to evaluate the impact of variations in daily temperature on
      the pest-control abilities of female Trichogramma and their immature progenies.
      Considering the temperature variability of different agricultural zones of India,
      five temperature levels ranging from 20oC to 40oC were selected for daily short
      term heat shocks to the immature progenies and egg-laying females of two major
      Trichogramma species. Intensity and frequency of thermal shocks showed inverse
      relationships with adult emergence, fecundity, and longevity of T. chilonis and
      T. poliae. Parasitoid pupae were found to be more tolerant to temperature
      variations than eggs and larvae. Fecundity and longevity of parasitoids were
      significantly reduced under high temperature shocks to egg-laying females. Sex
      ratio was significantly affected by high temperature shocks to the immature and
      adult stages. However, the effect was more severe in eggs. A female-biased sex
      ratio was apparent in both parasitoids throughout the experiment. Overall, daily
      short-term temperature shocks to different developmental stages of parasitoids
      showed radical effects on emergence, fecundity, longevity, and sex ratio of the
      progeny. Therefore, releases of parasitoids should be conducted when they are in
      their pupal stages during the morning and evening in order to achieve their
      highest effectiveness for pest management. 

PMID- 25373189
TI  - Comparative life tables of the potato tuberworm, Phthorimaea operculella, on
      leaves and tubers of different potato cultivars.
AB  - The potato tuberworm, Phthorimaea operculella Zeller (Lepidoptera: Gelechiidae),
      is a serious pest of the potato, Solanum tuberosum L. (Solanales: Solanaceae), in
      both fields and stores in tropical and subtropical regions. In the present study,
      the susceptibility of different potato cultivars to P. operculella was evaluated
      by measuring life table parameters. Tests were undertaken with leaves and tubers
      of 10 potato cultivars in the laboratory: Agria, Agata, Almera, Arinda, Baneba,
      Fiana, Marfona, Ramus, Satina, and Volvox. All parameters showed significant
      differences among tested cultivars. The longest mean generation times were
      observed on Marfona and Satina cultivars in the experiments on potato leaves and
      tubers, respectively. The lowest reproductive rate was observed on leaves and
      tubers of Marfona cultivar. Correspondingly, the lowest values of intrinsic rate
      of increase and the lowest finite rate of increase were also obtained on Marfona
      cultivar in tests on potato leaves and tubers. The highest intrinsic rate of
      incrase values were observed on Arinda and Baneba in the tests on leaves and
      tubers, respectively. The intrinsic rates of increase were significantly higher
      on potato leaves than on potato tubers. The lower performance of P. operculella
      on Marfona cultivar indicated that this cultivar is relatively less susceptible
      this pest and could be used in integrated pest management programs of P.
      operculella. 

PMID- 25373190
TI  - Development of microsatellite markers and detection of genetic variation between
      Goniozus wasp populations.
AB  - Molecular genetic markers reveal differences between genotypes according to the
      presence of alleles (the same or different) at target loci. Microsatellite
      markers are especially useful co-dominant markers that have been used in a wide
      range of studies to elucidate the population structure and dynamics of a range of
      organisms, including agriculturally beneficial insects such as parasitic wasps
      (parasitoids). In the present study, twelve primer pairs were designed for the
      south Asian , Goniozus nephantidis (Muesebeck) (Hymenoptera: Bethylidae), and 24
      for its New World congener, Goniozus legneri Gordh, parasitoids of the larvae of
      the lepidopteran coconut pest Opisina arenosella Walker (Lepidoptera:
      Crytophasidae) and other lepidopteran pests, respectively, in order to
      investigate polymorphism within and between populations. The wasps fingerprinted
      were a total of 85 G. nephantidis and G. legneri, including individuals belonging
      to three putatively different strains of G. legneri. Annealing gradient tests (50
      65 degrees C) were conducted to study the quality of the PCR amplification across
      an annealing temperature gradient using a mixed genotype DNA template from each
      species separately. Seven primer pairs, which amplified clear products of
      approximately the expected size of G. nephantidis and 18 of G. legneri, were then
      selected for capillary analysis for fragment size determination on a Beckmann CEQ
      8000. Neither G. nephantidis nor G. legneri were polymorphic within populations.
      However, there were six primer pairs that did show polymorphism between G.
      legneri populations that originated from different geographical areas within
      South America (Uruguay and Chile). Furthermore, one primer pair revealed
      diversity between the two strains collected within Chile. One of the markers was
      subsequently used to provide unbiased assessment of primary sex ratio in G.
      legneri. 

PMID- 25373191
TI  - Biology of the coconut bug, Pseudotheraptus wayi, on French beans.
AB  - The coconut bug, Pseudotheraptus wayi Brown (Heteroptera: Coreidae), is a major
      pest of a wide range of economically important crops in Eastern and Southern
      Africa. The suitability of French beans, Phaseolus vulgaris L. (Fabales:
      Fabaceae) as an alternative food for mass rearing of P. wayi was determined by
      elucidating its development, survival, and reproduction on French bean pods in
      the laboratory. Development and survival of immatures on French beans was
      comparable to what is reported with two hosts previously used for rearing this
      species, namely coconut and cashew. Adults survived thrice longer and laid almost
      twice more eggs on the French beans than was reported for the two hosts above.
      These findings suggest that French beans are more suitable for mass rearing of
      this species than coconut and cashew, which have been used previously but can be
      scarce and too costly. 

PMID- 25373192
TI  - Ultrastructure of the antennal sensillae of male and female peach fruit fly,
      Bactrocera zonata.
AB  - Antennal morphology and funicular sensillae of male and female peach fruit flies,
      Bactrocera zonata (Saunders) (Diptera: Tephritidae), were studied with scanning
      electron microscopy (SEM). This study focused on the sensillae found on the
      antennal segments (scape, pedicel, and flagellum or funiculus that bears the
      arista) of B. zonata. Antennal segments of females tended to be larger than those
      of the males. The first two antennal segments, scape and pedicel, were heavily
      covered with microtrichia and bear bristles. Numerous microtrichia as well as
      trichoid (I, II), basiconic, clavate, and coeloconic sensillae were observed on
      the funiculus. SEM studies showed some differences in size and also in position
      of some sensillae on the antennae of the females of B. zonata. The sensillae
      found on the funiculus, such as trichoid and basiconic sensillae, were
      significantly larger in females. 

PMID- 25373193
TI  - Pseudohampsonella: a new genus of Limacodidae (Lepidoptera: Zygaenoidea) from
      China, and three new species.
AB  - A new genus, Pseudohampsonella gen. n. (typespecies: Pseudohampsonella erlanga
      Solovyev & Saldaitis), and three new species, Pseudohampsonella erlanga sp. n.
      Solovyev & Saldaitis (from Sichuan Province, China), Pseudohampsonella hoenei sp.
      n. Solovyev & Saldaitis (Yunnan Province, China), and Pseudohampsonella argenta
      sp. n. Solovyev & Saldaitis (Yunnan Province, China) are described. The taxonomic
      position of the genus is discussed. 

PMID- 25373194
TI  - Viability of Cabralea canjerana extracts to control the South American fruit fly,
      Anastrepha fraterculus.
AB  - Several representatives of Meliaceae contain biologically active compounds that
      are toxic to insects with few negative effects on the environment and humans. Our
      study evaluated the activity of ethyl acetate and ethanol extracts from the fruit
      and seeds of Cabralea canjerana (Vellozo) Mart (Sapindales: Meliaceae) on
      Anastrepha fraterculus (Wiedemann) (Diptera: Tephritidae). Limonoids and
      triterpenes were detected in fruit and seed extracts. Each extract was added to
      an artificial diet at three concentrations and tested after 24, 48, and 72 hr of
      extract application. Ethyl acetate extracts were the most active ones and showed
      the effect of both dose and time elapses after application on the insects. The
      highest toxic effect on A. fraterculus adults was from ethyl acetate extracts
      from fruit, followed by extracts from seeds. These extracts showed antifeedant
      activities. Extract solutions sprinkled on fruits of Carica papaya (L.)
      (Brassicales: Caricaceae) caused oviposition repellency and negatively affected
      the biological development of A. fraterculus. Ethyl acetate extracts highly
      hampered oviposition, but seed extracts showed lesser oviposition deterrence. The
      fruit and seed extracts diminished pupal viability. Particularly, the ethyl
      acetate fruit extract caused malformed adults. The sex ratio was also affected,
      resulting in female predominance for the fruit extract, while the seed extract
      showed a dose-dependent effect. Low doses caused male abundance, but at higher
      concentrations the effect was reversed. These encouraging results showed that the
      C. canjerana extracts have great potential as new tools to be used in integrated
      pest management programs to protect fruits against A. fraterculus. 

PMID- 25373195
TI  - Food preference and foraging activity of ants: recommendations for field
      applications of low-toxicity baits.
AB  - Control of ants using baits of low toxicity cannot be effective without knowledge
      of bait distribution patterns and bait station densities, which are determined by
      ants' foraging activities. Furthermore, the success of toxic baits also depends
      upon attractiveness of bait carriers. Here, we assessed ground and vine foraging
      activity and food preferences for the three ant species ( Linepithema humile
      (Mayr) (Hymenoptera: Formicidae), Anoplolepis custodiens (F. Smith) and
      Crematogaster peringueyi Emery) under field conditions. We found that L. humile's
      vineyard foraging activity was high and that movement of ant bait by C.
      peringueyi and A. custodiens in the vineyard was relatively low. Consequently,
      more bait stations need to be dispensed for more effective control of C.
      peringueyi and A. custodiens than for L. humile. Different bait densities are
      discussed for the various ant species. Food preference trials indicated that
      vineyard foraging ants preferred wet bait attractants over dry ones, making
      liquids the most ideal carriers for baiting these ants. Linepithema humile was
      attracted to 25% sugar water, while C. peringueyi was attracted to both 25% sugar
      water and honey. Anoplolepis custodiens was attracted to tuna but was also
      attracted to 25% sugar water. Thus, future bait formulations should be tailor
      made to suit these specific food requirements if baits are to be successful in
      ant pest management. 

PMID- 25373196
TI  - Identification, rearing, and distribution of stick insects of Madeira Island: an
      example of raising biodiversity awareness.
AB  - Two species of stick insects are currently known to be present in the
      Macaronesian archipelagos: Clonopsis gallica (Charpentier) (Phasmatodea:
      Bacillidae) on the Canary Islands and in the Azores and Carausius morosus
      (Sinety) (Phasmatidae) in the Azores. Here, we provide the first reliable records
      of the presence and distribution of C. gallica and C. morosus on Madeira Island.
      Egg and adult stages are briefly described along with some notes on the life
      history of these species in captivity. Data on islandwide distribution are based
      on specimens donated by the public in response to an article published in a daily
      newspaper. This method of data collection raised great popular interest in stick
      insects. The role of newspapers as a means of communicating awareness in
      biodiversity issues is discussed. 

PMID- 25373197
TI  - Molecular characterization of fire ants, Solenopsis spp., from Brazil based on
      analysis of mtDNA gene cytochrome oxidase I.
AB  - Species from the Solenopsis saevissima (Smith) (Hymenoptera: Formicidae) species
      group are native to South America and have a cosmopolitan distribution because
      they have been accidentally introduced in many countries around the world. In
      Brazil, they have a wide distribution, including urban areas. The present study
      was conducted to investigate the characterization of Solenopsis genus populations
      associated with urban/human interference sites in Brazil by analyzing the
      mitochondrial gene cytochrome oxidase I and estimating the degree of relatedness
      of these populations to make inferences about their phylogeny and also observe
      the patterns of mitochondrial haplotype (mitotype) distribution across their
      range. The results revealed complete geographical coherence and polyphyly for the
      Solenopsis invicta Buren and Solenopsis saevissima species groups, which confirms
      the diversity of the genera. It also suggests the possibility that reproductively
      isolated populations occur, resulting in the evolutionary process of speciation.
      No predominant haplotype was found in the populations analyzed, but some were
      more prevalent. 

PMID- 25373198
TI  - Comparison of trends in habitat and resource selection by the Spanish Festoon,
      Zerynthia rumina, and the whole butterfly community in a semiarid Mediterranean
      ecosystem.
AB  - Butterfly community and single species based approaches were taken to establish
      conservation priorities within a nature reserve in Central Spain. In this study,
      patch type (sclerophyllous, halophilous, or disturbed), potential herbaceous
      nectar availability, potential woody plant nectar availability, total nectar
      availability, and two approximations to plant diversity (herbaceous and woody
      plant diversity) were evaluated as variables that account for adult butterfly
      density. Butterfly communities in the reserve, which consist mostly of generalist
      species, were denser in relatively wet areas dominated by halophilous vegetation.
      Diversity did not significantly vary between ecologically different transects.
      Total nectar availability correlated with higher butterfly densities within both
      undisturbed and disturbed areas, which could be primarily explained by the lack
      of water typical of semiarid Mediterranean climates, where fresh, nectariferous
      vegetation is scarce. Woody plants were also found to be important sources of
      nectar and shelter. In the dryer sclerophyllous sites, adult butterfly density
      was best explained by herbaceous plant diversity, suggesting better quality of
      available resources. The endangered specialist Zerynthia rumina (L.)
      (Lepidoptera: Papilionidae) was only present at the sclerophyllous sites. Its
      density was very low in all sampled transects, excluding one relatively isolated
      transect with high larval hostplant density. In contrast to the community-based
      approach, density of Z. rumina adults is better explained by the density of its
      larval hostplant than by nectar availability, a trend previously described for
      other sedentary species. Management strategies for protecting insect-rich areas
      should consider the specific ecological requirements of endangered species. 

PMID- 25373199
TI  - Courtship behavior of the castniid palm borer, Paysandisia archon: potential
      roles of male scents and visual cues in a day-flying moth.
AB  - The castniid palm borer, Paysandisia archon (Burmeister) (Lepidoptera:
      Castniidae), is a South American moth that in the last ten years has become a
      major pest of palm trees in the Mediterranean region. Current knowledge on the
      reproductive behavior of this diurnal moth suggests the importance of both visual
      and chemical cues, in particular the production of a male pheromone emitted
      during a specific scratching behavior. Male-produced scents have diverse
      functions in lepidopteran sexual communication but generally act during courtship
      behavior, leading to complex, stereotyped courtship sequences. As a first step to
      understand the cues involved in mating behavior and the role of male scents in
      male mating success, we quantified sequences of P. archon courtship behavior
      using video filming. To distinguish behaviors leading to an approach of both
      partners from those involved in short-range courtship, sequences were divided
      into "approach" and "interaction" phases. Quantifications and analyses were first
      made by NPMANOVA analysis of behavioral event frequencies, followed by flowchart
      construction using transition matrix probabilities. In 90% of the observations,
      courting activities led to copulation, but successful sequences were highly
      variable and could be divided into two categories, "rapid" and "prolonged"
      courtship sequences. In both categories, approaches were performed by males but
      depended strongly on female movements, especially on female flights. The
      significant behavioral differences were observed after the first contact (i.e.,
      interaction phase) where, in rapid sequences, males generally acceded to
      copulation without displaying scratching behavior. Conversely, in prolonged
      sequences, the female expressed evading behavior and male scratching frequency
      increased. The possible roles of male scent emission in female mate choice and
      the importance of visual cues in the mating behavior of P. archon are discussed. 

PMID- 25373200
TI  - Olfactory detection of prey by the termite-raiding antPachycondyla analis.
AB  - The African termiteraiding ant Pachycondyla analis Latreille (Hymenoptera:
      Formicidae) organizes group raids on termites of the subfamily Macrotermitinae.
      Termites and ants occupy and share similar habitats, resulting in a co
      evolutionary arms race between termites as prey and ants as predators. The
      present study explored whether P. analis uses semio- chemical signaling cues to
      detect potential termite prey prior to and during raids. Ants' responses to odors
      emitted from termites alone, termite gallery soil, and termites inside their
      galleries were tested using Y-tube olfactometer assays. The results showed that
      P. analis detected odors of termites and those of their galleries, and odors from
      termites inside their galleries were more attractive to both minor and major ant
      workers than odors from termites alone. The composition of these odor sources was
      identified using gas chromatography-mass spectrometry analysis. While the odors
      from termite gallery soils were compositionally richer (containing 13 compounds
      rather than nine from termites alone), those from the termites alone were
      quantitatively richer, releasing about six times more odors than gallery soil.
      Most of the compounds in the odor profiles were identified as hydrocarbons.
      Naphthalene, previously identified as an insect repellent, was also identified as
      a component of the odors from the gallery soil. These results demonstrate that
      odors play an important role in prey detection by P. analis. 

PMID- 25373201
TI  - Community structure of aquatic insects in the karstic Jadro River in Croatia.
AB  - This study focused on the aquatic insect community in the longitudinal gradient
      and temporal scales of the Jadro River. The river was sampled for a period of ten
      years (2000- 2010), four times per year through the various seasons, along the
      river course. Sampling stations were selected in the upper, middle, and
      downstream parts of the river. A total of 21,852 specimens of aquatic insects
      belonging to six orders were obtained. The species determination confirmed 27
      different species in the river. The data were analyzed by the multivariate
      methodologies of correspondence analysis and cluster analysis (unweighted pair
      group method with arithmetic mean) using the similarity index of Morosita for all
      ten years. Canonical correspondence analysis was applied to the data to check
      which of the mesured physicochemical variables significantly explained community
      variation. According to those data, significant variables for the upper station
      were water temperature and dissolved oxygen, and chlorides was the significant
      variable for the lower stations. 

PMID- 25373202
TI  - Carnivorous diving beetles of the genus Desmopachria (Coleoptera: Dytiscidae)
      from Brazil: new species, new records, and a checklist.
AB  - Eight new species of Desmopachria Babington, 1841 are described and illustrated
      from Brazil: D. dicrophallica sp nov., D. disticta sp nov., D. grammosticta sp
      nov., D. grandinigra sp nov., D. itamontensis sp nov., D. leptophallica sp nov.,
      D. stethothrix sp nov., and D. ukuki sp nov. The species D. amyae Miller, 2001,
      D. chei Miller, 1999, D. margarita Young, 1990, and D. volatidisca Miller, 2001
      are recorded for the first time from Brazil. From species of the Desmopachria
      reported in Brazil, D. aldessa Young, 1980 has a new record from Para state and
      D. fossulata Zimmermann, 1928, D. granoides Young, 1986, and D. laevis Sharp,
      1882 have new records from Rio de Janeiro State. A checklist of all Desmopachria
      recorded from Brazil is presented with notes about some of the localities.

PMID- 25373203
TI  - Expression of the nos gene and firefly flashing: a test of the nitric-oxide
      mediated flash control model.
AB  - Fireflies (Coleoptera: Lampyridae) emit various types of light that differ among
      species and populations of the same species. Their lights are assumed to be
      biological properties that play important ecological and evolutionary roles. Some
      species in the Lampyridae emit periodic luminescence, the patterns of which are
      characterized by species-specific intervals. In previous work, it was predicted
      that the nitric oxide (NO) regulates the oxygen supply required for the
      bioluminescence reaction of fireflies. Here, the expression of the NO synthase
      (NOS) mRNA in some fireflies was examined to verify the predictive model of
      nitric-oxide-mediated flash control in these insects. The expression of the nos
      gene in the lantern organ was observed not only in nocturnal flashing species but
      also in diurnal non-flashing species. It was shown that the expression levels of
      nos were higher in the lantern of Luciola cruciata (Motschulsky) larvae, which
      that emits continuous light, than in other body parts, although expression in the
      lantern of the adults, who flash periodically, was not high. Furthermore, there
      was no significant difference in expression levels among adults of Luciola
      cruciata characterized by different flashing intervals. The data do not support
      the model of an NO-mediated flash control mechanism, during which oxygen becomes
      available for the luciferin-luciferase reaction through NO-mediated inhibition of
      mitochondrial respiration. It is also indicated that flash patterns do not co
      vary with NOS production. However, high nos expression in the larval lantern
      suggests that NO may play a role in producing continuous light by functioning as
      a neurotransmitter signal for bioluminescence.

PMID- 25373204
TI  - Construction and analysis of cDNA libraries from the antennae of Batocera
      horsfieldi and expression pattern of putative odorant binding proteins.
AB  - A high-quality cDNA library was constructed from female and male antenna of the
      longhorned beetle, Batocera horsfieldi (Hope) (Coleoptera: Cerambycidae), a
      serious pest of Populus (Salicales: Salicaceae). The titer was approximately 2.37
      * 106 pfu/mL, and this complies with the test requirement. From the libraries,
      692 clones were selected randomly, sequenced, and further analyzed, and the
      recombinational efficiency reached 93.85%. By alignment and cluster analysis, we
      identified four odorant binding proteins, two pheromone-binding proteins (have
      the characteristic six conserved cysteine residues), four Minus-C odorant binding
      proteins (lost two conserved cysteines), and three chemosensory proteins. In this
      study, we describe the identification and characterization of four new cDNAs that
      encode Minus-C odorant binding proteins (Minus-C OBPs) from B. horsfieldi
      antennal cDNA libraries. Our investigation focused on the expression pattern of
      the Minus-C OBP genes in various tissues in both sexes at different developmental
      stages, using reverse transcription PCR (RT-PCR) and realtime PCR (qPCR)
      strategies. Minus-C OBP1, 2, and 3 were expressed in all tested tissues, with the
      exception of the head (without antenna, labial palps, and maxillary palps). Minus
      C OBP4 was expressed in the antenna, legs, and abdomen, but not in the labial
      palps, maxillary palps, or head. The qPCR results revealed MinusC OBPs were
      expressed in the antenna throughout the adult life, and that the transcript
      levels of these genes depended on the sex, age, and mating status of adults. 

PMID- 25373205
TI  - Depth and type of substrate influence the ability of Nasonia vitripennis to
      locate a host.
AB  - The foraging behaviour of a parasitoid insect species includes the host's habitat
      and subsequent location of the host. Habitats substrate, substrate moisture, and
      light levels can affect the host searching of different species of parasitoids.
      However, the depth at which parasitoids concentrate their search effort is
      another important ecological characteristic and plays an important role in
      locating a host. Here, we investigated the ability of a pupal parasitoid, Nasonia
      vitripennis Walker (Hymenoptera: Pteromalidae), to penetrate and kill fly pupae
      located at different depths of the substrate. Three different types of substrate
      were tested: loam soil, compost, and vermiculite substrate. In both loam soil and
      compost, all of the parasitism activity was restricted to pupae placed directly
      on the surface. Parasitism activity in vermiculite showed that the average number
      of pupae parasitized decreased with depth of substrate. These results suggest
      that fly pupae situated deeper in the substrate are less subjected to parasitism
      by N. vitripennis. 

PMID- 25373206
TI  - Stochastic modeling of economic injury levels with respect to yearly trends in
      price commodity.
AB  - The economic injury level (EIL) concept integrates economics and biology and uses
      chemical applications in crop protection only when economic loss by pests is
      anticipated. The EIL is defined by five primary variables: the cost of management
      tactic per production unit, the price of commodity, the injury units per pest,
      the damage per unit injury, and the proportionate reduction of injury averted by
      the application of a tactic. The above variables are related according to the
      formula EIL = C/VIDK. The observable dynamic alteration of the EIL due to its
      different parameters is a major characteristic of its concept. In this study, the
      yearly effect of the economic variables is assessed, and in particular the
      influence of the parameter commodity value on the shape of the EIL function. In
      addition, to predict the effects of the economic variables on the EIL level,
      yearly commodity values were incorporated in the EIL formula and the generated
      outcomes were further modelled with stochastic linear autoregressive models
      having different orders. According to the AR(1) model, forecasts for the five
      year period of 2010-2015 ranged from 2.33 to 2.41 specimens per sampling unit.
      These values represent a threshold that is in reasonable limits to justify future
      control actions. Management actions as related to productivity and price
      commodity significantly affect costs of crop production and thus define the
      adoption of IPM and sustainable crop production systems at local and
      international levels. 

PMID- 25373207
TI  - Interaction of Omega, Sigma, and Theta glutathione transferases with p38b mitogen
      activated protein kinase from the fruit fly, Drosophila melanogaster.
AB  - Glutathione S-transferases (GSTs) are a diverse family of phase II detoxification
      enzymes found in almost all organisms. Besides playing a major role in the
      detoxification of xenobiotic and toxic compounds, GSTs are also involved in the
      regulation of mitogen activated protein (MAP) kinase signal transduction by
      interaction with proteins in the pathway. An in vitro study was performed for
      Theta, Omega, Sigma GSTs and their interaction with MAP kinase p38b protein from
      the fruit fly Drosophila melanogaster Meigen (Diptera: Drosophilidae). The study
      included the effects of all five Omega class GSTs (DmGSTO1, DmGSTO2a, DmGSTO2b,
      DmGSTO3, DmGSTO4), all five Theta class GSTs (DmGSTT1, DmGSTT2, DmGSTT3a,
      DmGSTT3b, DmGSTT4), and one Sigma class glutathione transferase on the activity
      of Drosophila p38b, including the reciprocal effect of this kinase protein on
      glutathione transferase activity. It was found that DmGSTT2, DmGSTT3b, DmGSTO1,
      and DmGSTO3 activated p38b significantly. Substrate specificities of GSTs were
      also altered after co-incubation with p38b. Although p38b activated DmGSTO1,
      DmGSTO2a, and DmGSTT2, it inhibited DmGSTT3b and DmGSTO3 activity toward
      xenobiotic and physiological substrates tested. These results suggest a novel
      link between Omega and Theta GSTs with the p38b MAP kinase pathway. 

PMID- 25373208
TI  - Biology, temperature thresholds, and degree-day requirements for development of
      the cucumber moth, Diaphania indica, under laboratory conditions.
AB  - The cucumber moth, Diaphania indica (Saunders) (Lepidoptera: Pyralidae), is a
      tropical and sub-tropical cucurbits pest and a key greenhouse pest in the Jiroft
      region of Iran. In this study, the effect of different temperatures on the
      development of this pest was investigated on cucumber, Cucumis sativus L.
      (Cucurbitales: Cucurbitaceae), leaves in a growth chamber at various constant
      temperatures (20, 25, 30, and 35oC). The results indicated that the development
      period from egg to adult death at the decreased with increasing temperature.
      Mortality was greatest at 35oC. Based on a linear model, the highest and lowest
      temperature thresholds were recorded for male insects and pupal stage as 16oC and
      9.04oC with thermal constants of 100 and 144.92 degree days, respectively. 

PMID- 25373209
TI  - Population structure, genetic variability, and gene flow of the bean leaf beetle,
      Cerotoma trifurcata, in the Midwestern United States.
AB  - Bean leaf beetle, Cerotoma trifurcata (Forster) (Coleoptera: Chrysomelidae), is a
      common pest of soybean in the Midwest United States. However, there are currently
      no reports on the genetic variability of C. trifurcata. This study examined 15-30
      individuals from 25 sample locations to estimate genetic variability and gene
      flow within and among C. trifurcata from across the Mid- west. Amplified fragment
      length polymorphism generated 175 markers for analyses. Results from analysis of
      molecular variance (AMOVA) indicated that the majority of genetic variation was
      from within samples; only a small amount of the total variation was attributed to
      the variation among the samples. The GST for the entire C. trifurcata population
      indicated that the majority of genetic variation was found within the samples,
      further supporting the AMOVA results. The estimated average gene flow among the
      C. trifurcata samples was 1.83. The Mantel test revealed no indication of
      correlation between geographical and genetic distance for all the C. trifurcata
      samples. These findings show that C. trifurcata in the Midwest are genetically
      heterogeneous and part of a large, interbreeding population. 

PMID- 25373210
TI  - Identification and evaluation of suitable reference genes for gene expression
      studies in the whitefly Bemisia tabaci (Asia I) by reverse transcription
      quantitative realtime PCR.
AB  - This study presents a reliable method for performing reverse transcription
      quantitative realtime PCR (RT-qPCR) to measure gene expression in the whitefly
      Bemisia tabaci (Asia I) (Gennadius) (Hemiptera: Aleyrodidae), utilising suitable
      reference genes for data normalisation. We identified orthologs of commonly used
      reference genes (actin (ACT), cyclophilin 1 (CYP1), elongation factor 1alpha
      (EF1A), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), ribosomal protein L13a
      (RPL13A), and alpha-tubulin (TUB1A)), measured the levels of their transcripts by
      RT-qPCR during development and in response to thermal stress, and evaluated their
      suitability as endogenous controls using geNorm, BestKeeper, and NormFinder
      programs. Overall, TUB1A, RPL13A, and CYP1 were the most stable reference genes
      during B. tabaci development, and TUB1A, GAPDH, and RPL13A were the most stable
      reference genes in the context of thermal stress. An analysis of the effects of
      reference gene choice on the transcript profile of a developmentally-regulated
      gene encoding vitellogenin demonstrated the importance of selecting the correct
      endogenous controls for RT-qPCR studies. We propose the use of TUB1A, RPL13A, and
      CYP1 as endogenous controls for transcript profiling studies of B. tabaci
      development, whereas the combination of TUB1A, GAPDH, and RPL13A should be
      employed for studies into thermal stress. The data pre- sented here will assist
      future transcript profiling studies in whiteflies. 

PMID- 25373211
TI  - Trail marking by larvae of the cactus moth, Cactoblastis cactorum.
AB  - The cactus moth, Cactoblastis cactorum (Berg) (Lepidoptera: Pyralidae), spends
      most of its larval life feeding within the cladodes of Opuntia cactuses, but the
      gregarious caterpillars begin their life outside the plant, and in the later
      instars make intermittent excursions over plant surfaces to access new cladodes
      and to thermoregulate. The study reported here showed that when the caterpillars
      move en masse, they mark and follow trails that serve to keep the cohort
      together. Artificial trails prepared from hexane extracts of the caterpillar's
      paired mandibular glands were readily followed by the caterpillars. The glands
      are remarkably large, and their fluid contents, which constitute approximately 1%
      of the total wet mass of a caterpillar, are secreted onto the substrate as they
      move. Although the caterpillars also lay down copious quantities of silk, the
      material in itself neither elicits trail following nor is it a requisite
      component of pathways that elicit trail following. Previous analyses of the
      mandibular glands of other species of pyralid caterpillars showed that they
      contain a series of structurally distinct 2-acyl-1,3 cyclohexane diones. Chemical
      analysis indicates that the glands of C. cactorum contain structurally similar
      compounds, and bio- assays indicate that trail following occurs in response to
      these chemicals. While the mandibular glands' fluids have been shown to act as
      semiochemicals, effecting both interspecific and intra- specific behavior in
      other species of pyralids, the present study is the first to report their use as
      a trail pheromone.

PMID- 25373212
TI  - Purification and characterization of midgut alpha-amylase in a predatory bug,
      Andralus spinidens.
AB  - alpha-Amylases are widespread enzymes that catalyze endohydrolysis of long alpha
      1,4-glucan chains such as starch and glycogen. The highest amylolytic activity
      was found in 5th instar nymphs and midgut of the predatory bug, Andrallus
      spinidens F. (Hemiptera: Pentatomidae). The alpha-amylase was purified following
      a three-step procedure. The purified alpha-amylase had a specific activity of
      13.46 U/mg protein, recovery of 4.21, purification fold of 13.87, and molecular
      weight of 21.3 kDa. The enzyme had optimal pH and temperature of 7 and 45 degrees
      C, respectively. Na+, Mn+, Mg2+, and Zn2+ significantly decreased activity of the
      purified alpha-amylase, but some concentrations of K+, Ca2+, and Cu2+ had the
      opposite effect. EDTA, EGTA, and DTC significantly decreased enzymatic activity,
      showing the presence of metal ions in the catalytic site of the enzyme. Kinetic
      parameters of the purified alpha-amylase showed a Km of 3.71% in starch and 4.96%
      for glycogen, suggesting that the enzyme had a higher affinity for starch. 

PMID- 25373213
TI  - The genus Polystenus (Hymenoptera: Braconidae: Doryctinae) in China, with
      descriptions of two new species.
AB  - The species of Polystenus Foerster, 1862 (Hymenoptera: Braconidae: Doryctinae)
      from China are revised, and four species are recognized. Two new species, P.
      brevitergum sp nov. and P. taiwanus sp nov., are described and illustrated. A key
      to all species of the genus Polystenus is provided.

PMID- 25373215
TI  - Low temperature induces embryonic diapause in the spider mite, Eotetranychus
      smithi.
AB  - The spider mite, Eotetranychus smithi Pritchard & Baker (Acari: Tetranychidae),
      exhibits a facultative diapause that occurs at the egg stage. Diapause was
      induced by low temperatures alone (<= 17.5 degrees C) and averted by high
      temperatures (>= 20 degrees C). Photoperiod had little effect on diapause
      induction. This is the first example of temperature-induced diapause in spider
      mites. The diapause eggs became larger and darker (orange) than non- diapause
      eggs (white to pale yellow), suggesting that egg size and egg color are
      associated with diapause. When mites that were reared from eggs at 25 degrees C
      and 16:8 L:D were transferred to 15 degrees C and 16:8 L:D just after the start
      of the teleiochrysalis stage (the final molting stage before adulthood), all
      females laid non-diapause eggs during the first 30 days and then switched over to
      laying diapause eggs. The switch to diapause may be caused by the aging of
      mothers. 

PMID- 25373214
TI  - Effects of zinc on CarE activities and its gene transcript level in the English
      grain aphid, Sitobion avenae.
AB  - As a selective stress, heavy metals play an important role in inducing the
      adaptive adjustments of insects to changing environments. Carboxylesterase (CarE)
      is one kind of biomarker that could help us to explore the adaptation mechanism
      of aphids to heavy metal stress. In this study, CarE activity and gene expression
      level were investigated in English grain aphids, Sitobion avenae (F.) (Hemiptera:
      Aphididae), exposed to Zn2+ at concentrations of 0, 400, and 1600 mg/kg for 5,
      15, 25, and 30 generations. The results showed that the CarE activity was
      significantly different between different Zn2+ concentrations and different
      generations. The CarE activity significantly decreased with increasing
      generations. In the higher generations, the CarE activity was strongly inhibited
      by the 1600 mg/kg of Zn2+. Realtime quantitative PCR revealed that the CarE gene
      expression pattern in S. avenae was up-regulated under the condition of 400 mg/kg
      and 1600 mg/kg of Zn2+, but a significant difference was not found after long
      term exposure to high concentrations of Zn2+. It was concluded that CarE could be
      the sensitive biomarker for S. avenae response to the presence of Zn2+. In order
      to adapt to heavy metal Zn2+ stress, S. avenae had particular patterns of gene
      expression under long-term stress. 

PMID- 25373216
TI  - Aedes mosquito species in western Saudi Arabia.
AB  - The Aedes Meigen (Diptera: Culicidae) mosquito species populations in the western
      region of Saudi Arabia, especially in and around Jeddah, are increasing,
      therefore increasing susceptibility of humans to the dengue virus. An extensive
      survey was carried out for one year, and four species were identified with the
      help of different pictorial keys available. The identification was based on
      morphological characteristics of adult female Aedes mosquitoes. 

PMID- 25373217
TI  - Electrophysiological responses of the rice leaffolder, Cnaphalocrocis medinalis,
      to rice plant volatiles.
AB  - The rice leaffolder, Cnaphalocrocis medinalis Guenee (Lepidoptera: Pyralidae), is
      one of the most destructive pests of rice. Electrophysiological responses of this
      species to 38 synthetic volatiles known to be released from rice plants (Poaceae:
      Oryza spp.) were studied using the electroantennogram (EAG) method. Compounds
      that elicited the strongest EAG responses for each physiological condition were
      selected for EAG dose-response tests at five concentrations. These compounds
      included: methyl salicylate, heptanol, linalool, cyclohexanol, and 2-heptanone
      for one-day-old male moths; heptanol, hexanal, (Z)-2-hexen-1-ol, and nonadecane
      for one-day- old females; methyl salicylate, heptanol, (E)-2-hexen-1-ol, and (Z)
      2-hexen-1-ol for three-day- old males; linalool, heptanol, (E)-2-hexen-1-ol, 2
      heptanone, and hexanal for three-day-old females; 2-heptanone, cyclohexanol,
      linalool, heptanol, and methyl salicylate for five-day-old virgin females; and
      methyl benzoate, (Z)-2-hexen-1-ol, heptanol, linalool, and hexanal for five- day
      old mated females. Female and male C. medinalis exhibited broad overlap in their
      EAG responses, and there was no clear difference between male and female EAG
      responses to different compounds. Statistical analyses revealed that both
      volatile compound chemical structure and C. medinalis physiological condition
      (age, sex, and mating condition) had an effect on EAG response. 

PMID- 25373218
TI  - Revision of the genus Endochilus Weise (Coleoptera: Coccinellidae: Chilocorini).
AB  - The members of the endemic African genus Endochilus Weise, 1898 (Coleoptera:
      Coccinellidae: Chilocorini) are redescribed, diagnosed, and illustrated.
      Lectotypes are designated for Endochilus compater Weise, Endochilus minor Weise,
      Endochilus plagiatus Sicard, Endochilus rubicundus Weise, and Endochilus styx
      Sicard. One new species is described: Endochilus abdominalis sp nov. Notes on the
      genus and nomenclatural history for each species are provided. A key for
      identification of all species is presented. Adult characters concerning
      similarities of Endochilus to other genera of African Chilocorini are discussed.

PMID- 25373219
TI  - Qualitative and quantitative prey requirements of two aphidophagous coccinellids,
      Adalia tetraspilota and Hippodamia variegata.
AB  - The suitability of two prey species, Aphis pomi De Geer (Hemiptera: Aphididae)
      and Brevicoryne brassicae (L.), for two generalist aphidophagous coccinellids,
      Adalia tetraspilota (Hope) (Coleoptera: Coccinellidae) and Hippodamia variegata
      (Goeze), at various abundance levels was investigated under laboratory
      conditions. While both A. pomi and B. brassicae were found to be suitable, the
      predators performed better when feeding upon B. brassicae. The prey densities
      affected the developmental parameters of the two predators appreciably. Optimal
      growth and development was noted in the prey density range of 40-80 aphids per
      day per predator. Both species and abundance levels of prey significantly
      affected the larval period of the two predators. Appreciable variation in
      survivorship of larvae, prepupal and pupal period, and adult weight was noted by
      varying the prey species and prey abundance. Longer reproductive period
      (oviposition period) and shorter non-reproductive periods (preoviposition and
      postoviposition periods) were noted for females that fed on B. brassicae as
      compared to those that fed on A. pomi. Reproductive output was appreciably higher
      for females that fed on B. brassicae, and the fecundity decreased drastically
      under food shortage.

PMID- 25373220
TI  - Diversity and abundance of leafhoppers in Canadian vineyards.
AB  - Leafhoppers (Hemiptera: Cicadellidae) are pests of many temperate crops,
      including grapevines (Vitis species). Uncontrolled populations can induce direct
      and indirect damage to crops due to feeding that results in significant yield
      losses and increased mortality in infected vineyards due to virus, bacteria, or
      phytoplasmas vectored by leafhoppers. The main objective of this work was to
      determine the diversity of leafhoppers found in vineyards of the three main
      Canadian production provinces, i.e., in British Columbia, Ontario, and Quebec.
      Approximately 18,000 specimens were collected in 80 commercial vineyards from
      2006 to 2008. We identified 54 genera and at least 110 different species
      associated with vineyards, among which 22 were predominant and represented more
      than 91% of all the leafhoppers. Species richness and diversity were estimated by
      both Shannon's and Pielou's indices. For each province, results indicated a
      temporal variation in species composition. Color photographs provide a tool to
      quickly identify 72 leafhoppers commonly associated with vineyards. 

PMID- 25373221
TI  - Revision of Palearctic species of the genus Dimorphaphorura (Collembola:
      Onychiuridae: Onychiurinae: Oligaphorurini) with description of new species.
AB  - In this paper, the Palearctic genus Dimorphaphorura Bagnall, 1949 (Collembola:
      Onychiuridae), is revised. The diagnosis of the genus is defined within the tribe
      Oligaphorurini based on the development of the furcal area, shape of furcal
      rudiment, and furcal chaetotaxy. Six new species are described: D. olenae sp n.
      from Ukraine, D. inya sp n., D. pseudoinya sp n., D. sibirica sp n., D. caucasica
      sp n., and D. sophyae sp n. from Russia. The type species of the genus, D.
      differens Bagnall, 1949 is redescribed, and the lectotype and paralectotypes are
      designated. All previously known species are redescribed or with additional
      characters complemented: D. alnus (Fjellberg, 1987) comb n., D. chatyrdagi
      (Kaprus', Weiner & Pomorski, 2002) comb n., D. daii (Pomorski, Skarzynski &
      Kaprus', 1998) comb n., Dimorphaphorura eremia (Kaprus',Weiner & Pomorski, 2002)
      comb n., D. hackeri (Christian, 1986) comb n., D. irinae (Thibaud & Taraschuk,
      1997) comb n., D. melittae (Christian, 1993) comb n., D. pseudoraxensis (Nosek &
      Christian, 1983) comb n., D. raxensis (Gisin, 1961) comb n., D. steposa (Kaprus',
      Weiner & Pomorski, 2002). An identification key to all Dimorphaphorura species is
      provided.

PMID- 25373222
TI  - Fumigant, contact, and repellent activities of essential oils against the
      darkling beetle, Alphitobius diaperinus.
AB  - The fumigant, contact, and repellent activities of four essential oils extracted
      from Citrus limonum (Sapindales: Rutaceae), Litsea cubeba (Laurales: Lauraceae),
      Cinnamomum cassia, and Allium sativum L. (Asparagales: Alliaceae) against 6th
      instars and adults of the darkling beetle, Alphitobius diaperinus (Panzer)
      (Coleoptera: Tenebrionidae), one of the main pests of materials and products of
      Juncus effuses L. (Poales: Juncaceae) during the storage period, were assayed,
      and chemical ingredients were analyzed with gas chromatography-mass spectrometry
      in this study. While the major ingredients found in C. limonum and C. cassia were
      limonene and (E)-cinnamaldehyde, the main constituents of L. cubea were D
      limonene, (E)-3,7-dimethyl-,2,6-octadienal, (Z)-3,7-dimethyl,2 ,6-octadienal, and
      diallyl disulphide (18.20%), while the main constituents of and A. sativum were
      di-2-propenyl trisulfide and di-2-propenyl tetrasulfide. The fumigation
      activities of A. sativum and C. limonum on A. diaperinus adults were better than
      those of the other two essential oilss. The toxicities of A. sativum and C.
      limonum were almost equitoxic at 96 hr after treatment. Essential oils from
      Allium sativum and L. cubeba also showed good contact activities from 24 hr to 48
      hr, and toxicities were almost equitoxic 48 hr posttreatment. The repellent
      activities of A. sativum and L. cubeba oils on 6th instars were also observed,
      showing repellence indexes of 90.4% and 88.9% at 12 hr after treatment,
      respectively. The effects of A. sativum on AChE activity of 6th instars of A.
      diaperinus were strongest compared to the other essential oils, followed by C.
      limonum, L. cubeba, and C. cassia. These results suggest that the essential oils
      of C. limonum and A. sativum could serve as effective control agents of A.
      diaperinus.

PMID- 25373223
TI  - Expression analysis of several antiviral related genes to BmNPV in different
      resistant strains of silkworm, Bombyx mori.
AB  - Bombyx mori L. (Lepidoptera: Bombycidae) nucleopolyhedrovirus (BmNPV) is a highly
      pathogenic virus in the sericultural industry, often causing severe damage
      leading to large economic losses. The immune mechanisms of B. mori against this
      virus remain obscure. Previous studies had demonstrated Bmlipase-1, BmNox and
      Bmserine protease-2 showing antiviral activity in vitro, but data on the
      transcription levels of these proteins in different resistant strains were not
      reported. In order to determine the resistance level of the four different
      strains (P50, A35, A40, A53) and gain a better understanding of the mechanism of
      resistance to BmNPV in B. mori, the relative expression level of the genes coding
      the three antiviral proteins in larval haemolymph and midgut of different B. mori
      strains resistant to BmNPV was determined. The results showed that these genes
      expressed significantly higher in the resistant strains compared to the
      susceptible strain, and the differential expression levels were consistent with
      the LC50 values in different strains. The transcription level of the target genes
      almost all up-regulated in the larvae midgut and down-regulated in the
      haemolymph. The results indicate the correlation of these genes to BmNPV
      resistance in B. mori. 

PMID- 25373224
TI  - Small bait traps as accurate predictors of dipteran early colonizers in forensic
      studies.
AB  - Insect carrion communities vary among habitats and over time. Concerning the
      dipteran early colonizers of carrion, the use of small bait traps should be
      accurate because the odors emitted from meat baits should contain many of the
      volatile organic compounds emitted from the freshly dead mammals. In addition,
      this kind of trap is easy to replicate and set in position in a given habitat. In
      the present study, small bait preferences of early Diptera carrion colonizers
      were examined in an urban biotope. Specifically, three baits were compared (pork
      muscle, pork liver, and fish flavored cat food) in respect to the number of
      specimens and species captured and the presence or absence of oviposition at high
      and low environmental temperatures. A total of 2371 specimens were trapped,
      primarily belonging to three insect orders, Diptera, Coleoptera, and Hymenoptera.
      Diptera was the predominant order, with blowflies (Calliphoridae) being the most
      representative family, followed by filth flies (Muscidae). The pork muscle bait
      was responsible for the highest number of captures and the highest diversity. The
      community of Diptera collected with the most efficient bait, pork muscle, was
      compared with the carrion communities reported in the literature from the Iberian
      Peninsula. Similar taxonomic species composition was found regarding
      Calliphoridae species. A specimen from all species morphologically identified
      were also identified at a molecular level using the cytochrome c oxidase I (COI)
      barcode region, and the sequences were submitted to online databases. 

PMID- 25373225
TI  - Effects of temperature on the development and population growth of the melon
      thrips, Thrips palmi, on eggplant, Solanum melongena.
AB  - The effects of temperature on the melon thrips, Thrips palmi Karny (Thysanoptera:
      Thripidae), preimaginal development, survival, fecundity, longevity of females
      and males, and population growth were investigated at 16, 19, 22, 25, 28, and 31
      degrees  C, 70-80% RH, and a photoperiod of 12:12 L:D. The results indicated that
      the duration of egg, larval, and pupal stages was significantly influenced by
      increased temperature. The egg-to-adult developmental period of T. palmi declined
      from 35.7 to 9.6 days as the temperature increased from 16 to 31 degrees  C. The
      developmental threshold temperature estimated for egg-to-adult was 11.25 degrees 
      C, with a thermal constant of 196.1 degree-days. The developmental threshold
      temperature was 13.91, 11.82, 9.36, and 10.45 degrees  C for adult preoviposition
      period, total preoviposition period, female longevity, and male longevity,
      respectively. The thermal constants for completing the adult preoviposition
      period, total preoviposition period, female longevity, and male longevity were
      29.3, 227.3, 454.6, and 344.8 degree-days, respectively. Female longevity was
      found to be shortest at 31 degrees  C (18.7 days) and longest at 16 degrees  C
      (56.7 days), and male longevity was shortest at 31 degrees  C (15.5 days) and
      longest at 16 degrees  C (50.7 days). Fecundity was highest at 25 degrees  C
      (64.2 eggs/female) and lowest at 16 degrees  C (23.4 eggs/female). The population
      trend index of T. palmi was highest at 25 degrees  C (31.3) and lowest at 16
      degrees  C (7.6). The optimal developmental temperature for T. palmi in eggplant,
      Solanum melongena L. (Solanales: Solanaceae), was determined to be 25 degrees  C.

PMID- 25373237
TI  - [Current topics of diagnostic method-bronchoscopy-].

PMID- 25373226
TI  - Testing the potential of proposed DNA barcoding markers in Nezara virudula and
      Nezara antennata when geographic variation and closely related species were
      considered.
AB  - The COI gene as the core of the DNA barcoding system for animals has received
      significant attention. The observed wide overlap between intraand interspecific
      sequence variability has led researchers to envisage the primary COI-based
      method. The sequences of 16S rDNA, COI, and Cyt b genes of Nezara virudula (L.)
      (Hemiptera: Pentatomidae) from 13 countries and the same sequences of N.
      antennata Scott were chosen as molecular markers to analyze the intraand
      interspecific relationships between the closely related species in this study.
      The results support that Cyt b gene may be a good candidate alongside COI, when
      the combined factors of geographic variation and closely related species are
      taken into account. 

PMID- 25373238
TI  - [Current topics and future prospect for human papillomavirus infection-sinonasal
      cancer and HPV-].

PMID- 25373239
TI  - [Current progress for computer navigation surgery-current topics and future
      prospect for navigation surgery on sinus-].

PMID- 25373240
TI  - [Dysphasia for otolaryngologists role-swallowing training by otolaryngologist-].

PMID- 25373241
TI  - [Current topics for diagnosis method-gastrointestinal endoscopy-].

PMID- 25373242
TI  - [Robotics surgery for head and neck disease-TORS-].

PMID- 25373243
TI  - [Dysphasia for otolaryngologists role-effectiveness of surgical treatment].

PMID- 25373244
TI  - [Communication and presentation].

PMID- 25373245
TI  - 5-Hydroxytryptamine immunoreactivity  in the epidermal sacciform gland cells  of
      the clingfish Lepadogaster candollei Risso.
AB  - Summary. Serotonin has been demonstrated in the epidermal sacciform glandular
      cells of the clingfish Lepadogaster candollei by use of immunocytochemistry.
      Serotonin immunoreactivity is found both in the peripheral cytoplasm of the
      glandular cells and their luminal secretion.The presence of serotonin in the
      sacciform glandular cells parallels that located by both biochemical and
      immunocytochemicalproced procedures in the cutaneous glands of many amphibian
      species.

PMID- 25373246
TI  - The nutritional importance of liposoluble compounds, such as vitamin A. Foreword.

PMID- 25373247
TI  - Understanding differences and disorders of sex development. Foreword.

PMID- 25373248
TI  - Understanding differences and disorders of sex development. Preface.

PMID- 25373249
TI  - Catheter-related bloodstream infections: cost-effective strategies for
      prevention. Foreword.

PMID- 25373250
TI  - Effective strategies for reducing the incidence of catheter-related bloodstream
      infections.
AB  - Various prevalence surveys have revealed high rates of catheter-related
      bloodstream infection, which can cause patients so much harm and are expensive to
      treat. Yet most of these infections can be prevented with good practice. To this
      end, national guidelines and initiatives have been introduced outlining the
      procedures that will reduce infection rates. However, it is easy to be
      overwhelmed by the sheer number of recommendations. Care bundles were therefore
      created to identify the core group of procedures that must be adhered to in order
      to reduce infection rates. As a result, they have made it easier for health
      professionals to implement evidence-based practice. This article describes the
      care-bundle approach and how it has reduced infection rates. It also describes
      the latest recommendations on best practice, recently published in epic3, and
      outlines the issues staff and NHS organisations are likely to face when
      implementing them.

PMID- 25373251
TI  - The role of dressings in the prevention of vascular access device infections.
AB  - The risk of a catheter-related bloodstream infection (CRBSI) is an ever-present
      spectre for a patient with a vascular access device (VAD) in situ. The morbidity
      associated with these infections is high and incurs substantial costs. Worse
      still, thousands of patients with a VAD die of a CRBSI each year. Healthcare
      providers are championing the implementation of strategies that minimise or even
      eliminate the risk of CRBSIs, as these will improve patient outcomes and reduce
      healthcare costs. However, it is not only the financial implications of CRBSIs
      that must be considered. The impact of a CRBSI on the physical, emotional and
      mental wellbeing of a patient cannot be underestimated. This article will
      consider how the use of dressings can reduce the risk of CRBSI.

PMID- 25373252
TI  - Evaluating the cost-effectiveness of strategies to prevent vascular access device
      infections.
AB  - The evidence clearly indicates that a care-bundle approach is needed to prevent
      catheter-related bloodstream infections (CRBSIs). Such an approach includes the
      need for education, training and adequate staffing, sterile barrier precautions,
      skin preparation, use of intravenous dressings and antimicrobial prophylaxis.
      Care bundles advise which aspects must be given priority and what procedures will
      produce optimum outcomes. All of these activities come at a cost, yet very few
      studies have investigated the extent to which they are cost-effective. As a
      result, it is difficult to make evidence-based decisions on the potential cost
      savings that may be achieved with a care-bundle approach. This article describes
      the existing health-economic evidence on strategies to prevent CRBSIs and
      outlines the criteria for future research.

PMID- 25373253
TI  - Clinical experiences of using Biopatch: a chlorhexidine gluconate-impregnated
      sponge dressing. Case study 1: renal setting.

PMID- 25373254
TI  - Clinical experiences of using Biopatch: a chlorhexidine gluconate-impregnated
      sponge dressing. Case study 2: paediatric intensive care.

PMID- 25373256
TI  - [To exist].

PMID- 25373255
TI  - Clinical experiences of using Biopatch: a chlorhexidine gluconate-impregnated
      sponge dressing. Case study 3: paediatric care.

PMID- 25373257
TI  - [The dependence of the aging population - budget reform].

PMID- 25373258
TI  - [Medications crushed in food: increased risk of malnutrition].

PMID- 25373259
TI  - [Diminishing the fear of the loss of autonomy among the elderly].

PMID- 25373260
TI  - [Demotivation of the elderly].
AB  - Demotivation results from a pathological process that is not a part of normal
      ageing. It differs from a mood disorder, but it can often be associated with one.
      Linked to physical autonomy and/or mental losses, it can be a gateway to
      regression, increasing or establishing dependency.

PMID- 25373261
TI  - [Administration of drugs to the elderly and the nursing role].
AB  - Administration of medication in accommodation facilities for the elderly is not a
      trivial activity. This common action, effective but with a high risk of error,
      requires systematic precautions to be taken by each participant, including the
      nurses who are the ultimate link in the safety circuit. Collaboration of the
      professionals in the drug chain is a safety measure.

PMID- 25373262
TI  - [Sexuality and Alzheimer's in care facilities].
AB  - Sexuality of people with Alzheimer's disease is often prohibited in care
      facilities because its manitestations are considered harmful for the residents
      and the facility. Ethics of welfare implemented in care facilities require
      respect for the emotional and sexual lives of residents. Restoring sexual desire
      in care facilities can be achieved by adopting a humanistic approach that focuses
      on the development and personal fulfilment of individuals in every sphere of
      their lives, including sexuality.

PMID- 25373263
TI  - [Genito-urinary problems are not inevitable].

PMID- 25373264
TI  - [Urinary tract infections in the elderly].
AB  - In the elderly, urinary tract infections are frequent. Diagnosis is not always
      evident because symptoms are often absent. In doubt, a urinary strip evaluation
      must be performed. Prevention begins with simple lifestyle and dietary rules,
      such as good voiding and adequate fluid intake. Asymptomatic bacteriuria is
      treated only in certain cases. Other urinary tract infections require
      antibiotics, which must be adapted to renal function.

PMID- 25373265
TI  - [Urinary incontinence in the elderly].
AB  - Urinary incontinence affects approximately three million women in France. Its
      frequency increases with age. It impacts quality of life. Interrogation and
      clinical examination usually allow understanding its mechanism, but some
      additional explorations may be necessary. When a curative treatment is not
      possible, absorbent pads or a penile sheath in males improve patient comfort.

PMID- 25373266
TI  - [Benign prostatic hypertrophy and prostate cancer].
AB  - Prostatic diseases are extremely common, especially in older men. Amongst them,
      benign prostatic hypertrophy may affect significantly the quality of life of
      patients by the symptoms it causes. It requires appropriate care. Prostate cancer
      is the second most common cancer in men after lung cancer and the fifth leading
      cause of cancer deaths in the world. It affects preferentially older men. An
      oncogeriatric approach is required for personalised care.

PMID- 25373267
TI  - [Gynecological cancers in elderly women].
AB  - Pelvic gynaecological cancers are common in elderly women. Diagnosis and the
      decision to treat require multidisciplinary expertise. An oncologic, surgical and
      geriatric evaluation contributes to a split decision and personalised care. The
      care team is involved in the geriatric evaluation, information, education and
      patient monitoring throughout the treatment plan.

PMID- 25373268
TI  - [Kidney and bladder cancers in the elderly].
AB  - Kidney and bladder cancers are common in the elderly. Treatments used in younger
      patients may be considered for the latter, subject to an individual estimation of
      the/risk-benefit ratio that takes into consideration the geriatric evaluation
      parameters. Surgery is the only curative treatment for both cancers. Supportive
      care should be integrated early in comprehensive care to preserve the quality of
      life of elderly patients with these cancers.

PMID- 25373269
TI  - [Bibliography. Urogenital diseases in the elderly].

PMID- 25373270
TI  - [An episode of language difficulties].

PMID- 25373271
TI  - [Confusional syndrome].

PMID- 25373272
TI  - Back to basics: communication 101.

PMID- 25373273
TI  - Invasive aspergillosis in an allogeneic hematopoietic cell transplant patient.

PMID- 25373274
TI  - Acupuncture in cancer care.

PMID- 25373275
TI  - Metastatic colorectal cancer: management challenges and opportunities.
AB  - Median survival of patients with metastatic colorectal cancer (mCRC) has
      increased significantly, owing to individualized treatment plans developed from
      the available multidisciplinary options for disease management. These plans
      include early evaluation for possible resection of hepatic metastases, and
      metastasectomy, as well as coordinated chemobiotherapy for unresectable patients.
      This article focuses on current management of mCRC, including resection of liver
      metastases, which offers the possibility of cure to selected patients; sequential
      chemobiotherapy, which has been used effectively to increase median survival of
      patients with unresectable mCRC; the roles of neoadjuvant, conversion, and
      adjuvant chemobiotherapy in patients who undergo hepatic resection; and the
      emerging use of biomarkers to guide therapy. Implications for nurses are
      summarized, underscoring the important role that the nurse plays in the
      increasingly complex treatment of mCRC.

PMID- 25373276
TI  - The evolving care of metastatic colorectal cancer.

PMID- 25373277
TI  - Ipilimumab, a human monoclonal antibody for treatment of unresectable or
      metastatic melanoma.

PMID- 25373278
TI  - Evolution and opportunity.

PMID- 25373279
TI  - Fall risk assessment and prevention.
AB  - Patient falls are a common cause of morbidity and are the leading cause of injury
      deaths in adults age 65 years and older. Injuries sustained as result of falls in
      a cancer hospital are often severe, regardless of patient age, due to the nature
      of the underlying cancer. Falls are a nursing-sensitive indicator and nurses are
      in a unique position to assess, design, implement, and evaluate programs for fall
      risk reduction. We analyzed our nursing processes related to falls and fall
      prevention in conjunction with an evidence-based review, a research study to
      improve our fall risk-assessment process, and development of a comprehensive fall
      reduction program. This article outlines how our institution developed a fall
      risk assessment for the oncology patient population, and utilized this assessment
      in a comprehensive nursing approach to fall prevention in both inpatient and
      outpatient settings.

PMID- 25373280
TI  - Falls are key in patient assessment and planning.

PMID- 25373281
TI  - Counseling high-risk women about breast cancer.
AB  - Due to the rapidly evolving body of research in hereditary breast cancer, APNs
      are challenged to maintain their knowledge base and recognize which patients
      should be referred to a genetics specialist. Patients look to their APNs for
      answers and guidance. APNs are in a position to advocate for their patients and
      refer them for genetic counseling. Genetic counseling offers women at high risk
      for breast cancer the opportunity to make informed decisions about their choices
      for genetic testing and how they and their family members will utilize the
      potentially life-saving information.

PMID- 25373282
TI  - Care of the older adult with cancer: the geriatric oncology nursing imperative.

PMID- 25373283
TI  - Yoga.

PMID- 25373284
TI  - Eribulin, a microtubule inhibitor for metastatic breast cancer.

PMID- 25373285
TI  - [In Process Citation].

PMID- 25373287
TI  - [Intrahepatic cholestasis of pregnancy--ICP].

PMID- 25373286
TI  - [In Process Citation].

PMID- 25373288
TI  - [In Process Citation].

PMID- 25373289
TI  - [The seasonality of population contacts with medical organizations because of
      diseases of blood circulation system].
AB  - The comprehension of significance of health impacting of such unchangeable
      factors as climate and atmospheric phenomenons allows carrying out measures to
      decrease their negative effect on human health. The data of study implemented in
      Orel in 2009-2012 made it possible to distribute the annual totality of diagnoses
      registered in medical organizations on the groups of diseases of blood
      circulation system according ICD-10. The analysis established lower level of
      visits to physician because of these conditions both in ambulatory polyclinic
      institutions and hospital during summer period. The corresponding percentage came
      to 21.9% out of all diagnoses in polyclinic and 22% in hospital at highest levels
      of 27% in summer period. Therefore, in development of population contacts with
      medical organizations an expressed seasonality is detected. This occurrence is
      possibly related to characteristics of development of pathological conditions in
      different seasons.

PMID- 25373290
TI  - [The evaluation of health condition of first year students].
AB  - The study was organized to evaluate initial health condition and to detect risk
      factors of chronic diseases in first year students of University. The sampling
      consisted of 649 students aged from 15 to 30 years (mean age is 18.8 +/- 1.5
      years). The analysis of total morbidity demonstrated that 46.1% of first year
      students suffered from chronic diseases. It is noted that diseases of musculo
      skeletal system have especially high prevalence in students. The analysis of data
      of anonymous survey concerning behavioral risk factors established prevalence of
      tobacco smoking, alcohol consumption and sedentary life-style. Among students,
      23.5% of males and 9.3% of females smoked and correspondingly 28.5% and 12.5%
      took alcoholic drinks. The physical activity of students was insufficient and
      only one third of respondents follows healthy life-style. The group of healthy
      students consisted only 18.2% and 81.8% had different deviations i.e. risk
      factors of development of chronic diseases.

PMID- 25373291
TI  - [The development of obstetrics service in the Republic of Sakha (Yakutia)].
AB  - In the beginning of XX century health care of the Yakutskaya ASSR characterized
      by low level of development due to lacking and shortage of medical manpower,
      illiteracy of population in issues of prevention of various diseases. In those
      times, by virtue of timely applied new normative documents, health personnel
      training, organization of medical educational institution for Yakutia and
      preventive activities the first results in further development of obstetrics
      service were achieved. In the beginning of XX century in Yakutia high birth rate,
      high infant and maternal mortality were marked. The present study was carried out
      to analyze development of obstetrics service in Yakutskaya ASSR (at present the
      Republic of Sakha (Yakutia)). The study established that to the end of XX century
      birth rate decreased and extra genital morbidity increased. The indicators of
      perinatal and maternal mortality, quality indicators of dispensarization of
      pregnant women, prevention and diagnostic of diseases ameliorated. According
      implemented analysis no grounds are tracked to expect any increasing of birth
      rate. However, possibility is not inconceivable that in perspective percentage of
      women having two and more deliveries up to the end of reproductive cycle will
      decrease. The effectiveness of actual "stimlulating" measures of public policy
      will be under the threat in future because of "Russian cross" of 1996. In the
      Republic, aggregate birth rate level of 1.7 deliveries counting upon one woman
      has no perspective. The other mechanisms and public policy are needed to be
      worked out.

PMID- 25373292
TI  - [The social portrait of substitute families and modes of development of medical
      pedagogical monitoring].
AB  - The study demonstrated that in Russia the major cause of orphanage is a social
      life-style of biological parents of orphan children. The substitute families are
      more often large with number of children from 3 to 8 and quarter of them are
      incomplete. The mean age of substitute parent consists 47.8 +/- 1.4 years. The
      leading motivation to take orphan child/or education in family is the
      availability of kindred relationship regarding child or "deserted nest syndrome".
      At the initial phase of establishing of substitute family the most of substitute
      parents/tutors face with problems of health status and behavioral deviations of
      foster children. The substitute parents are unsatisfied with quality of medical
      monitoring of foster children. They also suffer fromdeficiency of information
      concerning characteristics of development, health conditions and modes of
      rehabilitation of children. In the judgment of substitute parents/tutors placing
      child into family conditions effects positively on one's development and health,
      behavior and emotional background. In substitute families, conditions organized
      for children can be named as approximated to conditions of residing in biological
      (home) families. The system of medical psychological and pedagogical monitoring
      of children of this category is needed in further development.

PMID- 25373293
TI  - [The approaches to investigation of factors impacting satisfaction of patients
      with medical care (according international publications' data].
AB  - The publications review analyzes factors impacting satisfaction with medical
      care. The principles of development of questionnaire are substantiated. The
      sociological instrument is targeted to detect such factors impacting satisfaction
      with medical care as flexibility in selection of patients, carrying out of focus
      groups of in-depth interviews with patients and literature analysis, possibility
      to combine qualitative and ordinal attributes as well as open questions,
      comfortability of respondent at the choice of ordinal scale and analysis of inner
      validity of questionnaire.

PMID- 25373294
TI  - [The waiting periods of ambulatory polyclinic care as indicator of its
      accessibility].
AB  - The article presents the results of analysis of waiting period of consultation of
      specialists in Moscow polyclinics exemplified by the ambulatory center of
      polyclinic No 201 of Moscow health department. The data of comparative analysis
      of indicators of polyclinics of different administrative okrugs of Moscow was
      also involved. The material was collected using the unified medical informative
      analytical system of polyclinic No 201 and included data concerning waiting
      periods of consultation of specialists with permitted self-appointment--surgeon,
      urologist, therapist, obstetrician-gynecologist and otorinolaringologist. The
      results of study demonstrated that the indicators of waiting period of
      consultation of specialists are highest in the Southern administrative okrug as
      compared with other okrugs. However, in one of amnulatory associations of this
      okrug (polyclinic Na 201) waiting period of consultation of obstetrician
      gynecologist, ophthalmologist, urologist and surgeon was reliably lower in
      comparison with corresponding okrug mean indicators. This occurrence is related
      to high support of association with these categories of specialists. The longest
      waiting period both in okrug and association was established for
      otorinolaringologisit (4.4 and 6.3 days correspondingly). This is related to low
      support of population with these specialists. The presented analysis of waiting
      period of consultation of specialists of polyclinic section is a foundation for
      adequate decisior making in health management targeted to increasing of
      accessibility of medical care to population.

PMID- 25373295
TI  - [The main directions of implementation of program of health care modernization in
      Moscow].
AB  - The article considers main-directions of development of Moscow health care
      including implementation of program of modernization of metropolitan health care
      and three-level system of medical care support of population.

PMID- 25373296
TI  - [The role of motivation of medical personnel in system of medical care quality
      support].
AB  - The article considers causes of insufficient quality of medical care. The low
      motivation of paramedical personnel during medical services rendering is
      examined. The sociological survey data made it possible to analyze opinion of
      students of medical college as future paramedical personnel concerning
      attractiveness of this profession. Their social and material status was
      established. The notions concerning possibility of carrier and professional
      progress were established too. The factors hampering involvement of this category
      of professionals into public health system and negatively impacting medical care
      quality were analyzed.

PMID- 25373297
TI  - [The organization of system of information support of regional health care].
AB  - The comparative analysis was implemented concerning versions of architecture of
      segment of unified public information system of health care within the framework
      of the regional program of modernization of Nizhniy Novgorod health care system.
      The author proposed means of increasing effectiveness of public investments on
      the basis of analysis of aggregate value of ownership of information system. The
      evaluation is given concerning running up to target program indicators and
      dynamics of basic indicators of informatization of institutions of oblast health
      care system.

PMID- 25373298
TI  - [The modern approaches to organization of delivery system in Nizhniy Novgorod].
AB  - The article presents data concerning reproductive demographic processes in
      Nizhniy Novgorod. The numbers of women of fertility age and indicator of
      maternity mortality were selected as objects for analysis. The structure of
      causes of maternal mortality is presented and on its basis the corresponding
      classification was developed. To prevent maternal losses the development of
      specialized centers was proposed and implementation of high-tech blood-preserving
      techniques as well. The routing and accompaniment of women being in critical
      ("closer to death") conditions are considered.

PMID- 25373299
TI  - [The accessibility of high-tech medical care of newborns with surgical pathology
      in conditions of Far North].
AB  - The actual stage of development of public health rendering of specialized medical
      care is based on principles of generality, accessibility, addressness,
      qualitativeness, and effectiveness. However, the problem of rendering specialized
      medical care to population is one of most critical targets in district centers
      and requires immediate solution. The main mean of resolving this problem is re
      hospitalization of patient in more large-scale medical institutions. The
      rendering of high-tech medical care, surgery care included, to newborns in the
      Republic of Sakha (Yakutia) is possible only in conditions of metropolitan health
      institutions i.e. medical institutions of third level. Annually, almost half of
      newborns with surgical pathology is transported from central district hospital.
      The organization of reanimation counseling center, maintenance of remote
      monitoring of newborns and development of telemedicine and means of sanitary
      aviation play main role in supporting accessibility of high-tech medical care in
      conditions of this region.

PMID- 25373300
TI  - [The problems of formation of competence of personnel of psychiatric service].
AB  - The article considers the category of competence of medical personnel of
      psychiatric service. The characteristics of focusing on professional activities
      in-psychiatry are analyzed. The problems of formation of professional competence
      of psychiatrists are considered.

PMID- 25373301
TI  - [The prevalence of intestinal parasites in children population of Baku].
AB  - The results of carried out studies demonstrated that children with intestinal
      parasitoses are more affected by different diseases than children without this
      pathology. In particular during last two years in the first group 78.2 +/- 1.5%
      of cases of diseases were registered while total children morbidity comes to 36.4
      +/- 2.0% of cases in average (t = 16.72, p < 0.001). Summarily, on each child
      with intestinal parasitoses accounts for 0.78 +/- 0.11% of cases of disease in
      average which resulted in 2.82 +/- 0.07 cases of missing school lessons. The rate
      of intestinal parasitoses is largely impacted by level of material well-fare and
      living conditions of families. The elimination of established social
      epidemiological prerequisites opens wide perspectives for organization and
      implementation of rational measures of prevention of intestinal parasitoses in
      urban children.

PMID- 25373302
TI  - [V.P. Kravkov as a sanitary physician of the Russian Imperial Army (to centenary
      of beginning of the First World War)].
AB  - The article presents for the first time the description of life story and service
      of V.P. Kravkov (1859-1920)--participant of Russian-Japanese war and the First
      World War, doctor of medicine, sanitary physician of the Russian Imperial Army
      and author of number of books and articles on preventive medicine. During these
      two wars, V.P. Kravkov organized sanitary epidemiological service in fronts. He
      kept diary regularly reflecting conditions of sanitary epidemiological service
      during this period, describing one's own observations and assessing survived
      events. The manuscripts of diaries are stored in the Russian state library. The
      diaries made great input into summarizing of experience of the Russian military
      sanitary service and became valuable monument of military memoirs' literature.

PMID- 25373303
TI  - [The sanitary education and propaganda in struggle with drunkenness and
      alcoholism in the USSR in 1920s].
AB  - The article considers the issue of sanitary education and anti-alcoholic
      propaganda in the USSR in 1920s and also forms and content of these activities.

PMID- 25373304
TI  - [The modeling of physiological systems of organism in 1970-1980s: to history of
      issue].
AB  - The article analyzes models, conditions, types and technologies of imitation
      modeling under investigations of physiological systems of organism
      (cardiovascular and respiratory systems) in 1970-1980s. The results of study are
      presented concerning history of application of imitation model during elaboration
      of algorithms and programs in clinic for treatment, objective need and advantages
      of this technique under implementation as an additional tool of physician for
      proper decision making.

PMID- 25373305
TI  - The importance of spectral separation: an assessment of dual-energy spectral
      separation for quantitative ability and dose efficiency.
AB  - INTRODUCTION: One method to acquire dual-energy (DE) computed tomography (CT)
      data is to perform CT scans at 2 different x-ray tube voltages, typically 80 and
      140 kV, either as 2 separate scans, by means of rapid kV switching, or with the
      use of 2 x-ray sources as in dual-source CT (DSCT) systems. In DSCT, it is
      possible to improve spectral separation with tin prefiltration (Sn) of the high
      kV beam. Recently, x-ray tube voltages beyond the established range of 80 to 140
      kV were commercially introduced, which enable additional voltage combinations for
      DE acquisitions, such as 80/150 Sn or 90/150 Sn kV. Here, we investigate the DE
      performance of several x-ray tube voltages and prefilter combinations on 2 DSCT
      scanners and the impact of the spectra on quantitative analysis and dose
      efficiency. MATERIALS AND METHODS: Circular phantoms of different sizes (10-40 cm
      in diameter) equipped with cylindrical inserts containing water and diluted
      iodine contrast agent (14.5 mg/cm) were scanned using 2 different DSCT systems
      (SOMATOM Definition Flash and SOMATOM Force; Siemens AG, Forchheim, Germany).
      Five x-ray tube voltage combinations (80/140 Sn, 100/140 Sn, 80/150 Sn, 90/150
      Sn, and 100/150 Sn kV) were investigated, and the results were compared with the
      previous standard acquisition technique (80/140 kV). As an example, 80/140 Sn kV
      means that 1 x-ray tube of the DSCT system was operated at 80 kV, whereas the
      other was operated at 140 kV with additional tin prefiltration (Sn). Dose values
      in terms of computed tomography dose index (CTDIvol) were kept constant between
      the different voltage combinations but adjusted with regard to object size
      according to automatic exposure control recommendations. Reconstructed images
      were processed using linear blending of the low- and high-kV CT images to
      combined images, as well as 3-material decomposition techniques to generate
      virtual noncontrast (VNC) images and iodine images. Contrast and pixel noise were
      evaluated, as well as DE ratios, which are defined as the CT value at low kV
      divided by the CT value at high kV. RESULTS: For the 10-, 20-, 30-, and 40-cm
      phantom, dose values in terms of CTDIvol were 1.2, 2.6, 7.3, and 21.6 mGy,
      respectively. In the combined images, those obtained with tin filtration showed
      lower noise values at similar iodine enhancement levels than did images obtained
      without tin filtration. The largest differences in noise were observed for the
      larger phantoms, in particular the 40-cm phantom. Dual-energy ratios for iodine
      increased with decreasing voltages of the low-kV beam and with increasing
      voltages of the high-kV beam, and they increased when tin prefiltration was
      added. In case of the 20-cm phantom, DE ratios ranged from 2.0 at 80/140 kV to
      3.4 at 80/150 Sn kV. The noise level of the VNC images was strongly correlated
      with the inverse of the DE ratio. Irrespective of the phantom size, the lowest
      noise values were measured for 80/150 Sn kV. DISCUSSION: Dual-source CT systems
      enable DE data to be acquired using a variety of voltage combinations. Combined
      (or mixed) DE images provide an image impression similar to standard 120 kV
      images, yet the noise level depends on the DE voltage combination that is
      selected. Noise in decomposed VNC images is strongly influenced by the DE ratio,
      and it improves substantially with tin filtration of the high-voltage beam.

PMID- 25373306
TI  - N-Myc downstream-regulated gene 2 suppresses proliferation and induces oncosis of
      OS-RC-2 human renal cancer cells.
AB  - V-myc avian myelocytomatosis viral oncogene homolog (Myc) regulates cell
      proliferation, differentiation and apoptosis in several types of cancer. N-myc
      downstream-regulated gene 2 (NDRG2) is known to exhibit reduced expression in
      renal cell carcinoma (RCC) tissues compared with adjacent non-neoplastic tissues
      and is an independent poor prognostic factor predicting survival in RCC. In the
      present study, green fluorescent protein (GFP)-NDRG2 and control GFP recombinant
      adenovirus plasmids were constructed and used to infect human renal cancer (OS-RC
      2) cells. NDRG2 expression was measured using western blot analysis and the
      subcellular localization of NDRG2 was detected using confocal microscopy. The
      rate of proliferation of the cells was measured using colony formation and MTT
      assays, and the cell cycle was analyzed using flow cytometry. The results showed
      that the OS-RC-2 cells expressed little NDRG2 prior to infection with GFP-NDRG2
      recombinant adenovirus; however, following infection, NDRG2 was found to be
      overexpressed, primarily in the mitochondria. The proliferation rate of the OS-RC
      2 cells was reduced by NDRG2. Approximately 84.8% of the NDRG2-expressing cells
      were in S phase compared with 58.7% in the control virus-infected cells (P<0.05).
      In addition, the upregulation of NDRG2 induced a higher proportion of OS-RC-2
      cells to undergo oncosis instead of apoptosis. In conclusion, the results from
      this study suggest that NDRG2 expressed in mitochondria may arrest renal cancer
      cells in S phase, decrease cell proliferation and induce oncosis. This indicates
      that NDRG2 is not only a biomarker, but may also be a therapeutic target for the
      treatment of RCC.

PMID- 25373307
TI  - Multicolor (Vis-NIR) mesoporous silica nanospheres linked with lanthanide
      complexes using 2-(5-bromothiophen)imidazo[4,5-f][1,10]phenanthroline for in
      vitro bioimaging.
AB  - A novel mesoporous nanosphere functionalized with 3-(aminopropyl)triethoxysilane
      (APTES) and 2-(5-bromothiophen)imidazo[4,5-f][1,10]phenanthroline (5-Br-Tip) was
      synthesized (denoted as Tip-MSS). With the coordinating function of the 5-Br-Tip
      to lanthanide (Ln) ions, for the first time, LnL3(5-Br-Tip) complexes were linked
      to the mesoporous nanospheres. The derived materials, named Ln-Tip-MSS (Ln = Eu,
      Tb, Sm, Nd, Yb), were characterized by Fourier-transform infrared (FT-IR)
      spectroscopy, TEM, XRD (wide-angle and small-angle), N2 adsorption/desorption
      analysis, and fluorescence spectroscopy. Upon excitation in the ligand
      absorption, the Ln-Tip-MSS nanomaterials show characteristic visible (Eu, Tb, Sm)
      and NIR (Sm, Nd, Yb) luminescence (multicolor emission covered from 450 nm to
      1400 nm spectral region). Of importance is that, with low cytotoxicity and good
      biocompatibility given by the methyl thiazolyl tetrazolium (MTT) assay, the Eu
      Tip-MSS was successfully applied to cell imaging in vitro based on the Eu(3+)
      luminescence (under 405 nm excitation). 

PMID- 25373308
TI  - Hepatic uptake of epirubicin by isolated rat hepatocytes and its biliary
      excretion after intravenous infusion in rats.
AB  - Anthracycline anticancer agents are widely used in the cancer chemotherapy for
      hepatocelluar carcinoma. However, accurate kinetic analyses of the hepatocellular
      uptake and efflux of the drugs have not been reported. We, therefore,
      investigated the hepatobiliary transport of epirubicin, an anthracycline derived
      antibiotic, after intravenous (i.v.) infusion in rats. The hepatic uptake
      mechanisms of epirubicin were also investigated in isolated rat hepatocytes. To
      analyze epirubicin levels in the biological samples, we used an HPLC-based method
      which has been validated for a kinetic study by suitable criteria. The uptake
      process of epirubicin by the hepatocytes revealed one saturable component, with a
      Km of 99.1 MUg/mL and Vmax of 3.70 MUg/min/10(6) cells. The initial uptake
      velocity of epirubicin was significantly inhibited in a temperature-dependent
      manner. The velocity was also reduced in the presence of metabolic inhibitors
      such as rotenone or carbonylcyanide-p-(trifluoromethoxy)-phenylhydrazone.
      Substrates for organic anion transporters such as bromosulfophthalein and
      taurocholate significantly inhibited the initial uptake velocity of epirubicin.
      We also attempted to determine the hepatobiliary transport of epirubicin after
      i.v. infusion in vivo. At steady-state after i.v. infusion of epirubicin (10-160
      MUg/min/kg), the drug was extensively accumulated in the liver, followed by
      excretion into bile. Furthermore, the CLbile,plasma and CLbile,liver decreased
      with a corresponding increase in the Css,plasma and Css,liver. In conclusion,
      present studies using isolated rat hepatocytes and in vivo i.v. infusion
      demonstrate that epirubicin is likely to be taken up into liver cells via organic
      anion transporting polypeptides, and that its biliary excretion might be mediated
      via specific transporters.

PMID- 25373309
TI  - Enantioseparation and chiral recognition of alpha-amino acids and their
      derivatives on (-)-18-crown-6-tetracarboxylic acid bonded silica by capillary
      electrochromatography.
AB  - Capillary electrochromatography was employed for enantioseparation of alpha-amino
      acids and their derivatives. (-)-18-Crown-6-2,3,11,12-tetracarboxylic acid bonded
      on the silica was used as the chiral stationary phase and methanol/Tris-citric
      acid (20 mM, pH 3.0-4.5) (20:80, v/v) was used as mobile phase. The
      enantioseparation performance was discussed and structure-chiral separation
      relationship were tried to be explained. The enantiomeric resolution was
      increased when the pH of the mobile phase decreased or hydrogen of amino acid was
      substituted with halogen. The resolution of 4-bromophenylalanine was 2.37 at pH
      4.5, however, this value was increased to 3.35 at pH 3.0. Bromo- or chloro
      substituted phenylalanine tended to show higher resolution than fluoro
      substituted one. For fluoro-substituted phenylalanine the resolution was
      increased in order of 4-, 3- and 2-substituted one. alpha-Methyltryptamine did
      not show reasonable separation. As the thermodynamic study is a useful tool to
      understand the chiral recognition, the temperature effect on the
      enantioseparation was studied and the thermodynamic parameters were calculated.
      The most important mechanism of chiral recognition for the analytes tested could
      be barrier effects based on the thermodynamic calculations. The coefficient of
      determination between hydrophobicity and separation factor was found to be 0.87,
      indicating favorable separation with higher hydrophobicity of amino acids.

PMID- 25373311
TI  - The failing Ebola policy.

PMID- 25373310
TI  - Perforin-dependent direct cytotoxicity in natural killer cells induces
      considerable knockdown of spontaneous lung metastases and computer modelling
      proven tumor cell dormancy in a HT29 human colon cancer xenograft mouse model.
AB  - BACKGROUND: For long, natural killer (NK) cells have been suspected to play a
      critical role in suppressing the development of spontaneous metastases in cancer
      patients. Despite a wide range of studies it remains unclear so far to what
      extent primary tumor growth together with formation of distant metastases and NK
      cell activity influence each other. METHODS: To precisely investigate the role of
      NK cells with a perforin-deficiency in cancer growth and metastasis formation,
      human HT29 colon cancer cells were subcutaneously grafted into pore forming
      protein and recombination activating gene 2 double knock out (pfp/rag2) mice and
      in recombination activating gene 2 only knock out (rag2) mice both with black six
      background. Both mice lack B and T cell functions due to the absence of rag2.
      RESULTS: Primary tumors developed in 16/16 in pfp/rag2 and 20/20 rag2 mice. At
      sacrifice primary tumor weight did not differ significantly. However, tumors grew
      faster in pfp/rag2 mice (50 days) than in pfp/rag2 mice (70 days). Circulating
      tumor cells (CTC) in murine blood were nearly three times higher in pfp/rag2 (68
      cells/ml) than in rag2 mice (24 cells/ml). Lung metastases occurred frequently in
      pfp/rag2 mice (13/16) and infrequently in rag2 mice (5/20). The mean number of
      metastases was 789 in pfp/rag2 mice compared to 210 in rag2 mice. Lung metastases
      in pfp/rag2 mice consisted of 10-100 tumor cells while those in rag2 mice were
      generally disseminated tumor cells (DTCs).Computer modelling showed that perforin
      dependent killing of NK cells decelerates the growth of the primary tumour and
      kills 80% of CTCs. Furthermore, perforin-mediated cytotoxicity hampers the
      proliferation of the malignant cells in host tissue forcing them to stay dormant
      for at least 30 days. CONCLUSION: The results exactly quantified the effect of
      perforin-dependent direct cytotoxicity of NK cells on HT29 on primary tumor
      growth, number of CTCs in the blood and the number of metastases. The largest
      effects were seen in the number of mice developing spontaneous lung metastases
      and the mean number of lung metastases. Hence, perforin-mediated cytotoxicity
      used for direct killing by NK cells is more important than indirect killing by
      secretion of death-inducing ligands by NK cells.

PMID- 25373312
TI  - Peptide-MHC multimer-based monitoring of CD8 T-cells in HIV-1 infection and AIDS
      vaccine development.
AB  - The use of MHC multimers allows precise and direct detecting and analyzing of
      antigen-specific T-cell populations and provides new opportunities to
      characterize T-cell responses in humans and animals. MHC-multimers enable us to
      enumerate specific T-cells targeting to viral, tumor and vaccine antigens with
      exceptional sensitivity and specificity. In the field of HIV/SIV immunology, this
      technique provides valuable information about the frequencies of HIV- and SIV
      specific CD8(+) cytotoxic T lymphocytes (CTLs) in different tissues and sites of
      infection, AIDS progression, and pathogenesis. Peptide-MHC multimer technology
      remains a very sensitive tool in detecting virus-specific T -cells for evaluation
      of the immunogenicity of vaccines against HIV-1 in preclinical trials. Moreover,
      it helps to understand how immune responses are formed following vaccination in
      the dynamics from priming point until T-cell memory is matured. Here we review a
      diversity of peptide-MHC class I multimer applications for fundamental
      immunological studies in different aspects of HIV/SIV infection and vaccine
      development. 

PMID- 25373313
TI  - Establishing a food list for a Total Diet Study: how does food consumption of
      specific subpopulations need to be considered?
AB  - A Total Diet Study (TDS) consists of selecting, collecting and analysing commonly
      consumed foods to obtain concentration data of different chemical compounds in
      foods as eaten. A TDS food list summarises the most consumed foods and represents
      the dietary habits of the general population of the country under study. The work
      reported here investigated whether TDS food lists that were initially designed
      for the whole population of the country under study also sufficiently cover the
      dietary pattern of specific subpopulations that are extra vulnerable for certain
      contaminants. The work was performed using data of three European countries: the
      Czech Republic, France and the UK. Each national food consumption database was
      combined with the corresponding national TDS food list (containing 336, 212 and
      119 food items for the Czech Republic, France and the UK, respectively). The data
      were aggregated on the highest level of hierarchy of FoodEx-1, a pan-European
      food classification system, including 20 main FoodEx-1 groups. For the group
      'milk and dairy products', the coverage of the consumption by the food list was
      investigated for more refined subgroups. For each food group or subgroup and
      country, the average percentage of coverage of the diet by the national TDS food
      list was calculated for different subpopulations, including children versus
      adults, women versus men, vegetarians versus non-vegetarians, and women of child
      bearing age versus older women. The average diet of the different subpopulations
      was sufficiently covered by the food list of the Czech Republic and France. For
      the UK the average coverage was low due to a different food-coding approach and
      because food lists were not derived directly from national food consumption data.
      At the level of the 20 main food groups, differences between the subpopulations
      with respect to the average coverage of consumption by the TDS food list were
      minimal. The differences were more pronounced when looking in detail at the
      coverage of the dairy consumption. TDS food lists based on the mean consumption
      of the general population are also applicable to study the chemical exposure of
      different subpopulations, e.g. children, women of child-bearing age and
      vegetarians. This lowers the effort when performing a TDS. 

PMID- 25373314
TI  - Exploring the efficacy of replacing linear paper-based patient cases in problem
      based learning with dynamic Web-based virtual patients: randomized controlled
      trial.
AB  - BACKGROUND: Problem-based learning (PBL) is well established in medical education
      and beyond, and continues to be developed and explored. Challenges include how to
      connect the somewhat abstract nature of classroom-based PBL with clinical
      practice and how to maintain learner engagement in the process of PBL over time.
      OBJECTIVE: A study was conducted to investigate the efficacy of decision-PBL (D
      PBL), a variant form of PBL that replaces linear PBL cases with virtual patients.
      These Web-based interactive cases provided learners with a series of patient
      management pathways. Learners were encouraged to consider and discuss courses of
      action, take their chosen management pathway, and experience the consequences of
      their decisions. A Web-based application was essential to allow scenarios to
      respond dynamically to learners' decisions, to deliver the scenarios to multiple
      PBL classrooms in the same timeframe, and to record centrally the paths taken by
      the PBL groups. METHODS: A randomized controlled trial in crossover design was
      run involving all learners (N=81) in the second year of the graduate entry stream
      for the undergraduate medicine program at St George's University of London.
      Learners were randomized to study groups; half engaged in a D-PBL activity
      whereas the other half had a traditional linear PBL activity on the same subject
      material. Groups alternated D-PBL and linear PBL over the semester. The measure
      was mean cohort performance on specific face-to-face exam questions at the end of
      the semester. RESULTS: D-PBL groups performed better than linear PBL groups on
      questions related to D-PBL with the difference being statistically significant
      for all questions. Differences between the exam performances of the 2 groups were
      not statistically significant for the questions not related to D-PBL. The effect
      sizes for D-PBL-related questions were large and positive (>0.6) except for 1
      question that showed a medium positive effect size. The effect sizes for
      questions not related to D-PBL were all small (<=0.3) with a mix of positive and
      negative values. CONCLUSIONS: The efficacy of D-PBL was indicated by improved
      exam performance for learners who had D-PBL compared to those who had linear PBL.
      This suggests that the use of D-PBL leads to better midterm learning outcomes
      than linear PBL, at least for learners with prior experience with linear PBL. On
      the basis of tutor and student feedback, St George's University of London and the
      University of Nicosia, Cyprus have replaced paper PBL cases for midstage
      undergraduate teaching with D-PBL virtual patients, and 6 more institutions in
      the ePBLnet partnership will be implementing D-PBL in Autumn 2015.

PMID- 25373315
TI  - Efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung
      cancer: a systematic review and meta-analysis.
AB  - PURPOSE: Vascular endothelial growth factor signaling pathway plays a crucial
      role in angiogenesis and has become a promising target for cancer drug
      development. We aimed to quantify the overall efficacy and safety of angiogenesis
      inhibitors in advanced non-small cell lung cancer (NSCLC). METHODS: Electronic
      databases were searched for randomized controlled trials (RCTs) comparing
      angiogenesis inhibitors with non-angiogenesis inhibitors for NSCLC patients. The
      extracted data on objective response rates (ORRs), disease control rates (DCRs),
      progression-free survival (PFS) and overall survival (OS) were pooled. Common
      adverse events (AEs) were also studied. RESULTS: A total of 33 RCTs involving
      17,396 patients were included. Compared with non-angiogenesis inhibitors,
      angiogenesis inhibitors resulted in significant improvement in PFS (HR, 0.81; 95
      % CI 0.76-0.85; p < 0.001), OS (HR, 0.95; 95 % CI 0.92-0.98; p = 0.004), ORR (RR,
      1.54; 95 % CI 1.37-1.73; p < 0.001) and DCR (RR, 1.18; 95 % CI 1.10-1.27; p <
      0.001). The AEs associated with angiogenesis inhibitors were generally
      predictable and manageable. CONCLUSION: Angiogenesis inhibitors were superior to
      non-angiogenesis inhibitors in terms of ORR, DCR, PFS and OS in advanced NSCLC
      patients. Further studies are warranted to explore the predictive biomarkers to
      pick up those who may gain utmost benefit from anti-angiogenic therapy.

PMID- 25373316
TI  - Proteinase-activated receptor 1- and 4-promoted migration of Hep3B hepatocellular
      carcinoma cells depends on ROS formation and RTK transactivation.
AB  - PURPOSE: There is growing evidence for a role of proteinase-activated receptors
      (PARs), a subfamily of G protein-coupled receptors, in cancer. We have previously
      shown that PAR1 and PAR4 are able to promote the migration of hepatocellular
      carcinoma (HCC) cells suggesting a function in HCC progression. In this study, we
      assessed the underlying signalling mechanisms. METHODS: Using Hep3B liver
      carcinoma cells, RTK activation was assessed by Western blot employing phospho
      RTK specific antibodies, ROS level were estimated by H2DCF-DA using confocal
      laser scanning microscopy, and measurement of PTP activity was performed in cell
      lysates using 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP) as a
      substrate. RESULTS: Thrombin, the PAR1 selective agonist peptide TFLLRN-NH2 (PAR1
      AP), and the PAR4 selective agonist peptide, AYPGKF-NH2 (PAR4-AP), induced a
      significant increase in Hep3B cell migration that could be blocked by inhibitors
      targeting formation of reactive oxygen species (ROS), or activation of hepatocyte
      growth factor receptor (Met), or platelet-derived growth factor receptor (PDGFR),
      respectively. The involvement of these intracellular effectors in PAR1/4
      initiated migratory signalling was further supported by the findings that
      individual stimulation of Hep3B cells with the PAR1-AP and the PAR4-AP induced an
      increase in ROS production and the transactivation of Met and PDGFR. In addition,
      PAR1- and PAR4-mediated inhibition of total PTP activity and specifically PTP1B.
      ROS inhibition by N-acetyl-L-cysteine prevented the inhibition of PTP1B
      phosphatase activity induced by PAR1-AP and the PAR4-AP, but had no effect on
      PAR1/4-mediated activation of Met and PDGFR in Hep3B cells. CONCLUSIONS:
      Collectively, our data indicate that PAR1 and PAR4 activate common promigratory
      signalling pathways in Hep3B liver carcinoma cells including activation of the
      receptor tyrosine kinases Met and PDGFR, the formation of ROS and the
      inactivation of PTP1B. However, PAR1/4-triggered Met and PDGFR transactivation
      seem to be mediated independently from the ROS-PTP1B signalling module.

PMID- 25373317
TI  - Effect of galectin-3 on the behavior of Eca-109 human esophageal cancer cells.
AB  - Galectin-3, a beta-galactoside-binding lectin, is a cell adhesion molecule
      involved in the regulation of tumor progression. However, the importance of
      galectin-3 in Eca-109 human esophageal cancer cells has not yet been elucidated.
      In the present study, a lentiviral vector was designed for overexpression of
      galectin-3 in Eca-109 cells following plasmid-mediated transfection (Eca-109/Gal
      3 cells). A negative lentiviral vector was introduced into Eca-109 cells as a
      control (Eca-109/Neo cells). Western blot and reverse transcription-polymerase
      chain reaction analyses were used to measure the expression levels of galectin-3
      protein and mRNA. The proliferation of Eca-109 cells was measured by a cell
      counting kit-8 assay. Eca-109 cell apoptosis was determined by Annexin V/7-amino
      actinomycin double-staining. The migration and invasion capacity of Eca-109 cells
      was determined by a Transwell assay. A total of >98% Eca-109 cells were
      transfected with the lentiviral vector harboring galectin-3, and galectin-3
      expression was detected in Eca-109 cells, Eca-109/Gal-3 cells and Eca-109/Neo
      cells. Compared with non-transfected and negative control Eca-109 cells,
      proliferation was increased significantly in the Eca-109/Gal-3 cells (P<0.05).
      Galectin-3 also significantly reduced Eca-109 cell apoptosis, compared with the
      two control groups (P=0.007 and P=0.04, respectively). Transwell migration and
      invasion assays revealed that significantly greater numbers of Eca-109/Gal-3
      cells crossed the artificial basement membrane (55.4+/-3.9) compared with either
      the non-transfected or negative control Eca-109 cells (30.6+/-1.5 and 29+/-2.6
      respectively, P<0.05). In conclusion, galectin-3 expression was significantly
      increased in transfected Eca-109 esophageal cancer cells, resulting in enhanced
      proliferation, migration and invasion, as well as reduced apoptosis. These data
      indicate that galectin-3 may be a potential molecular target in the treatment of
      esophageal cancer. 

PMID- 25373318
TI  - Mesenchymal stem cell technology in the treatment of degenerative disc disease.
AB  - AIM: Low back pain is the leading cause of disability and a major health problem
      around the world. As of today, symptomatic relief is the best option offered to
      patients, with mixed results. This study will review the use of mesenchymal stem
      cell (MSC) technology in the conservative and surgical treatments of degenerative
      disc disease (DDD). METHODS: A series of PubMed-National Library of Medicine
      searches were performed. Only articles in English journals or with published with
      English language translations were included. Level of evidence of the selected
      articles was assessed. RESULTS: There are multiple in-vitro and animal studies
      describing successful intervertebral disc (IVD) repair/regeneration with the use
      of live MSC therapy. Only 3 human studies (22 patients) with inconsistent results
      have been performed using bone marrow MSCs injected into diseased IVDs in
      patients with DDD. There exist multiple in-vitro and animal studies describing
      successful bony fusion with the use of MSC-containing bone graft substitutes.
      Only 3 retrospective human studies (115 patients) using CBM in spinal fusion have
      been performed with successful fusion rates ranging from 90.2%-92.3%. However,
      these studies lacked power and had significant conflicts of interest. There are
      multiple challenges with the use of MSC technology in humans. CONCLUSION: MSCs
      may be a promising therapy in the treatment of DDD. However, their lack of
      success in human models leaves room for further research and focus in this field.
      Currently, there is no clinical evidence to support the use of this technology in
      the conservative or surgical management of patients with DDD.

PMID- 25373319
TI  - Effects of insulin on human pancreatic cancer progression modeled in vitro.
AB  - BACKGROUND: Pancreatic adenocarcinoma is one of the most lethal cancers, yet it
      remains understudied and poorly understood. Hyperinsulinemia has been reported to
      be a risk factor of pancreatic cancer, and the rapid rise of hyperinsulinemia
      associated with obesity and type 2 diabetes foreshadows a rise in cancer
      incidence. However, the actions of insulin at the various stages of pancreatic
      cancer progression remain poorly defined. METHODS: Here, we examined the effects
      of a range of insulin doses on signalling, proliferation and survival in three
      human cell models meant to represent three stages in pancreatic cancer
      progression: primary pancreatic duct cells, the HPDE immortalized pancreatic
      ductal cell line, and the PANC1 metastatic pancreatic cancer cell line. Cells
      were treated with a range of insulin doses, and their proliferation/viability
      were tracked via live cell imaging and XTT assays. Signal transduction was
      assessed through the AKT and ERK signalling pathways via immunoblotting.
      Inhibitors of AKT and ERK signalling were used to determine the relative
      contribution of these pathways to the survival of each cell model. RESULTS: While
      all three cell types responded to insulin, as indicated by phosphorylation of AKT
      and ERK, we found that there were stark differences in insulin-dependent
      proliferation, cell viability and cell survival among the cell types. High
      concentrations of insulin increased PANC1 and HPDE cell number, but did not alter
      primary duct cell proliferation in vitro. Cell survival was enhanced by insulin
      in both primary duct cells and HPDE cells. Moreover, we found that primary cells
      were more dependent on AKT signalling, while HPDE cells and PANC1 cells were more
      dependent on RAF/ERK signalling. CONCLUSIONS: Our data suggest that excessive
      insulin signalling may contribute to proliferation and survival in human
      immortalized pancreatic ductal cells and metastatic pancreatic cancer cells, but
      not in normal adult human pancreatic ductal cells. These data suggest that
      signalling pathways involved in cell survival may be rewired during pancreatic
      cancer progression.

PMID- 25373320
TI  - Intravenous iron alone resolves anemia in patients with functional iron
      deficiency and lymphoid malignancies undergoing chemotherapy.
AB  - This randomized trial evaluated ferric carboxymaltose without erythropoiesis
      stimulating agents (ESA) for correction of anemia in cancer patients with
      functional iron deficiency. Patients on treatment for indolent lymphoid
      malignancies, who had anemia [hemoglobin (Hb) 8.5-10.5 g/dL] and functional iron
      deficiency [transferrin saturation (TSAT) <= 20%, ferritin >30 ng/mL (women) or
      >40 ng/mL (men)], were randomized to ferric carboxymaltose (1,000 mg iron) or
      control. Primary end point was the mean change in Hb from baseline to weeks 4, 6
      and 8 without transfusions or ESA. Difficulties with patient recruitment led to
      premature termination of the study. Seventeen patients (8 ferric carboxymaltose
      and 9 control) were included in the analysis. In the ferric carboxymaltose arm,
      mean Hb increase was significantly higher versus control at week 8 (p = 0.021).
      All ferric carboxymaltose-treated patients achieved an Hb increase >1 g/dL
      (control 6/9; p = 0.087), and mean TSAT was >20% from week 2 onwards. No
      treatment-related adverse events were reported. In conclusion, ferric
      carboxymaltose without ESA effectively increased Hb and iron status in this small
      patient population.

PMID- 25373321
TI  - Autologous hematopoietic stem cell transplantation for relapsed follicular
      lymphoma: safety profile and clinical outcome in a single-center experience.
AB  - Autologous hematopoietic stem cell transplantation (AHSCT) is a treatment option
      for relapsed and recurrent follicular lymphoma (R/R FL); however, its value in
      the rituximab era remains to be elucidated. To evaluate the safety and clinical
      outcome of AHSCT for relapsed FL, we present a retrospective series of AHSCT for
      30 FL patients (17 male and 13 female) at median age of 49 years. Patients were
      transplanted in second or subsequent complete or partial response after at least
      one therapeutic line including chemotherapy and rituximab. Overall, seven
      patients achieved second or higher complete response (CR) at AHSCT, whereas 23
      were transplanted in partial response. Median overall survival (OS) was not
      reached, whereas progression-free survival (PFS) was 4.8 years. The estimated 10
      year OS and PFS were found to be 60 and 33%, respectively. There was no
      significant difference in OS and PFS in terms of FLIPI score and disease status
      at transplant. Median follow-ups from diagnosis and from AHSCT were 4.9 years
      (range 1.5-18.4 years) and 1.7 years (range 0.03-16.5 years), respectively.
      Fifteen patients relapsed, and 11 out of them (73%) died of disease recurrence
      and chemoresistance. At the last contact, 19 patients are alive: 12 are in CR,
      whereas seven patients receive salvage regimens due to active lymphoma. AHSCT for
      relapsed FL patients who were pretreated with rituximab remains a safe procedure
      with low transplant-related mortality and long-term progression-free survival in
      about one-third of transplanted patients.

PMID- 25373323
TI  - Gene expression profiling of histologically normal breast tissue in females with
      human epidermal growth factor receptor 2-positive breast cancer.
AB  - Gene expression profile-based taxonomy of breast cancer (BC) has been described
      as a significant breakthrough in comprehending the differences in the origin and
      behavior of cancer to allow individually tailored therapeutic approaches. In line
      with this, we hypothesized that the gene expression profile of histologically
      normal epithelium (HNEpi) could harbor certain genetic abnormalities predisposing
      breast tissue cells to develop human epidermal growth factor receptor 2 (HER2)
      positive BC. Thus, the aim of the present study was to assess gene expression in
      normal and BC tissue (BCTis) from patients with BC in order to establish its
      value as a potential diagnostic marker for cancer development. An array study
      evaluating a panel of 84 pathway- and disease-specific genes in HER2-positive BC
      and tumor-adjacent HNEpi was performed using quantitative polymerase chain
      reaction in 12 patients using microdissected samples from frozen tissue. Common
      prognostic and predictive parameters of BC were assessed by immunohistochemistry
      and in situ hybridization. In the BCTis and HNEpi samples of 12 HER2-positive
      subjects with BC, the expression of 2,016 genes was assessed. A total of 39.3% of
      genes were deregulated at a minimal two-fold deregulation rate and 10.7% at a
      five-fold deregulation rate in samples of HNEpi or BCTis. Significant differences
      in gene expression between BCTis and HNEpi samples were revealed for BCL2L2,
      CD44, CTSD, EGFR, ERBB2, ITGA6, NGFB, RPL27, SCBG2A1 and SCGB1D2 genes (P<0.05),
      as well as GSN, KIT, KLK5, SERPINB5 and STC2 genes (P<0.01). Insignificant
      differences (P<0.07) were observed for CCNA1, CLU, DLC1, GABRP and IL6 genes. The
      ontological gene analyses revealed that the majority of the deregulated genes in
      the HNEpi samples were part of the functional gene group directly associated with
      BC origin and prognosis. Functional analysis showed that the most frequent gene
      deregulations occurred in genes associated with apoptosis and cell cycle
      regulation in BCTis samples, and with angiogenesis, regulation of the cell cycle
      and transcriptional activity in HNEpi samples. The molecular profiling of HNEpi
      breast tissue revealed gene expression abnormalities that may represent potential
      markers of increased risk for HER2-positive malignant transformation of breast
      tissue, and may be able to be employed as predictors of prognosis.

PMID- 25373322
TI  - Clinical value of serum HMGB1 in diagnosis and prognosis of laryngeal squamous
      cell carcinoma.
AB  - Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancies
      in the head and neck region. Recently, aberrantly expressed high-mobility group
      box 1 (HMGB1) has received a great deal of attention as a potential biomarker for
      cancer diagnosis and prognosis. Therefore, the aim of this study was to estimate
      HMGB1 levels in serum in LSCC patients and healthy controls and evaluated the
      potential of serum HMGB1 as a noninvasive biomarker for diagnosis and prognosis
      in LSCC. Serum HMGB1 levels were analyzed in 71 LSCC patients and 50 healthy
      controls. The serum HMGB1 level was significantly higher in LSCC patients
      compared with the healthy controls (4.81 +/- 2.33 vs. 3.21 +/- 1.08 ng/mL, P <
      0.001). High serum HMGB1 was significantly associated with T classification (P =
      0.005), N classification (P = 0.002), and clinical stage (P = 0.001). The area
      under ROC curve was 0.716, and the sensitivity and specificity were 42.3 and
      92.0%, respectively. The Kaplan-Meier plots showed that patients with high serum
      HMGB1 had a poorer overall survival than those with low serum HMGB1 (P = 0.036).
      Serum HMGB1 levels are significantly associated with the progression of LSCC. In
      this population, HMGB1 has a poor sensitivity, but a high specificity for the
      diagnosis of LSCC. Serum HMGB1 level has potential as a biomarker for the
      prognosis in LSCC patients.

PMID- 25373324
TI  - High temperature thermoelectric properties of the type-I clathrate Ba8NixGe46-x
      y?y.
AB  - Polycrystalline samples of the type-I clathrate Ba(8)Ni(x)Ge(46-x-y)?(y) were
      synthesized for 0.2 ? x ? 3.5 by melt quenching and for 3.5<x ? 6.0 by melting
      with subsequent annealing at 700  degrees C. The maximum Ni content in the
      clathrate framework at this temperature was found to be x ~ 4.2 atoms per unit
      cell. Thermoelectric and thermodynamic properties of the type-I clathrate were
      investigated from 300 to 700 K by means of electrical resistivity, thermopower,
      thermal conductivity and specific heat measurements. As the Ni content increases,
      the electronic properties gradually evolve from a metallic character (x < 3.5)
      towards a highly doped semiconducting state (x ? 3.5). Below x ~ 4.0 transport is
      dominated by electrons, while further addition of Ni (x ~ 4.2) switches the
      electrical conduction to p-type. Maximum value of the dimensionless
      thermoelectric figure of merit ZT ~ 0.2 was achieved at 500 K and 650 K for x ~
      2.0 and x ~ 3.8, respectively.

PMID- 25373325
TI  - Enhanced helical folding of ortho-phenylenes through the control of aromatic
      stacking interactions.
AB  - The ortho-phenylenes are a simple class of foldamers, with the formation of
      helices driven by offset aromatic stacking interactions parallel to the helical
      axis. For the majority of reported o-phenylene oligomers, the perfectly folded
      conformer comprises perhaps 50-75% of the total population. Given the hundreds or
      thousands of possible conformers for even short oligomers, this distribution
      represents a substantial bias toward the folded state. However, "next-generation"
      o-phenylenes with better folding properties are needed if these structures are to
      be exploited as functional units within more complex architectures. Here, we
      report several new series of o-phenylene oligomers, varying both the nature and
      orientation of the substituents on every repeat unit. The conformational behavior
      was probed using a combination of NMR spectroscopy, DFT calculations, and X-ray
      crystallography. We find that increasing the electron-withdrawing character of
      the substituents gives oligomers with substantially improved folding properties.
      With moderately electron-withdrawing groups (acetoxy), we observe >90% of the
      perfectly folded conformer, and stronger electron withdrawing groups (triflate,
      cyano) give oligomers for which misfolded states are undetectable by NMR. The
      folding of these oligomers is only weakly solvent-dependent. General guidelines
      for the assessment of o-phenylene folding by NMR and UV-vis spectroscopy are also
      discussed. 

PMID- 25373326
TI  - Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes
      in the tapeworm Moniezia expansa.
AB  - The sheep tapeworm Moniezia expansa is very common parasite, which affects
      ruminants such as sheep, goats as well as other species. The benzimidazole
      anthelmintics albendazole (ABZ), flubendazole (FLU) and mebendazole (MBZ) are
      often used to treat the infection. The drug-metabolizing enzymes of helminths may
      alter the potency of anthelmintic treatment. The aim of our study was to assess
      the activity of the main drug-metabolizing enzymes and evaluate the metabolism of
      selected anthelmintics (ABZ, MBZ and FLU) in M. expansa. Activities of
      biotransformation enzymes were determined in subcellular fractions. Metabolites
      of the anthelmintics were detected and identified using high performance liquid
      chromatography/ultra-violet/VIS/fluorescence or ultra-high performance liquid
      chromatography/mass spectrometry. Reduction of MBZ, FLU and oxidation of ABZ were
      proved as well as activities of various metabolizing enzymes. Despite the fact
      that the conjugation enzymes glutathione S-transferase, UDP-glucuronosyl
      transferase and UDP-glucosyl transferase were active in vitro, no conjugated
      metabolites of anthelmintics were identified either ex vivo or in vitro. The
      obtained results indicate that sheep tapeworm is able to deactivate the
      administered anthelmintics, and thus protects itself against their action. 

PMID- 25373328
TI  - Inverse probability weighting and doubly robust methods in correcting the effects
      of non-response in the reimbursed medication and self-reported turnout estimates
      in the ATH survey.
AB  - BACKGROUND: To assess the nonresponse rates in a questionnaire survey with
      respect to administrative register data, and to correct the bias statistically.
      METHODS: The Finnish Regional Health and Well-being Study (ATH) in 2010 was based
      on a national sample and several regional samples. Missing data analysis was
      based on socio-demographic register data covering the whole sample. Inverse
      probability weighting (IPW) and doubly robust (DR) methods were estimated using
      the logistic regression model, which was selected using the Bayesian information
      criteria. The crude, weighted and true self-reported turnout in the 2008
      municipal election and prevalences of entitlements to specially reimbursed
      medication, and the crude and weighted body mass index (BMI) means were compared.
      RESULTS: The IPW method appeared to remove a relatively large proportion of the
      bias compared to the crude prevalence estimates of the turnout and the
      entitlements to specially reimbursed medication. Several demographic factors were
      shown to be associated with missing data, but few interactions were found.
      CONCLUSIONS: Our results suggest that the IPW method can improve the accuracy of
      results of a population survey, and the model selection provides insight into the
      structure of missing data. However, health-related missing data mechanisms are
      beyond the scope of statistical methods, which mainly rely on socio-demographic
      information to correct the results.

PMID- 25373329
TI  - Sialidase production and genetic diversity in Clostridium perfringens type A
      isolated from chicken with necrotic enteritis in Brazil.
AB  - The sialidase activity and genetic diversity of 22 Clostridium perfringens
      strains isolated from chickens with necrotic enteritis were determined. Sialidase
      activity was detected in 86.4 % of the strains. All C. perfringens showed a high
      value of similarity (>96 %), and they were grouped into seven clusters clearly
      separated from the other reference bacterial strains. From these clusters four
      patterns were defined in accordance with their phenotypic (sialidase production
      and antibiotic resistance profile) and genotypic (presence of nanI and nanJ
      genes) characteristics. Our results showed heterogeneity among strains, but they
      were genotypically similar, and it is suggested further studies are needed to
      better understand the pathogenesis of necrotic enteritis.

PMID- 25373330
TI  - Vulnerability of motorcycle riders and co-riders to injuries in multi-occupant
      crashes.
AB  - In developing countries, most motorcycles are ridden with more than one occupant.
      The objective of this study was to establish the relative vulnerability of riders
      and co-riders to injury and determine the injury risk factors in multi-occupant
      motorcycle crashes. Between January and December 2010, we collected crash and
      injury data from victims of multi-occupant motorcycle. It is a hospital-based
      study. The probability of sustaining injuries was similar for co-riders and
      riders, but co-riders were more likely to sustain severe injuries. Occupants of
      >2-occupant motorcycles were also more likely to be involved in risky behaviours
      like not wearing helmet and speeding than those on 2-occupant motorcycles.
      Occupants of motorcycles on which there were more than two occupants were at an
      increased risk of sustaining injuries compared with occupants of motorcycles with
      only two occupants (OR: 2.1, 95% CI: 1.1-4.3). Motorcycle co-riders were more
      vulnerable to severe injuries than riders. The significance of the study finding
      to prevention was discussed. 

PMID- 25373331
TI  - Success in publication by graduate students in psychiatry in Brazil: an empirical
      evaluation of the relative influence of English proficiency and advisor
      expertise.
AB  - BACKGROUND: This study evaluates the success of graduate students in psychiatry
      in an emerging country, in terms of the quantity and quality of their publication
      productivity (given by the number of papers and impact factors of the journals in
      which they publish). We investigated to what extent student proficiency in
      English and the scientific capabilities of academic advisors predict that
      success. METHODS: Our sample comprised 43 master's and doctoral students in
      psychiatry (n = 28 and n = 15, respectively) at the University of Sao Paulo
      School of Medicine, in Sao Paulo, Brazil. We collected information about their
      knowledge of English and the ways in which they wrote their articles to be
      submitted to periodicals published in English. Multiple regression analyses were
      carried out in order to investigate the influence English proficiency, h-index of
      supervisors and use of language editing assistance had on the number and impact
      of student publications. RESULTS: Although 60% of students scored >=80 (out of
      100) on English tests given at admission to the graduate program, 93.09% of the
      sample used some form of external editing assistance to produce their papers in
      English. The variables "number of publications" and "impact factor of journals"
      were significantly related to each other (r = 0.550, p < 0.001). Multiple
      regression analysis revealed that the impact factor of periodicals where students
      published their articles as first authors correlated significantly not only with
      student proficiency in English at admission (p = 0.035), but also with the degree
      of language editing assistance (p = 0.050) and the h-index of the academic
      advisor (p = 0.050). CONCLUSIONS: Albeit relevant, knowledge of English was not
      the key factor for the publication success of the graduate students evaluated.
      Other variables (h-index of the advisor and third-party language editing
      assistance) appear to be also important predictors of success in publication.

PMID- 25373332
TI  - Community composition of known and uncultured archaeal lineages in anaerobic or
      anoxic wastewater treatment sludge.
AB  - Microbial systems are widely used to treat different types of wastewater from
      domestic, agricultural, and industrial sources. Community composition is an
      important factor in determining the successful performance of microbial treatment
      systems; however, a variety of uncultured and unknown lineages exist in sludge
      that requires identification and characterization. The present study examined the
      archaeal community composition in methanogenic, denitrifying, and nitrogen
      /phosphate-removing wastewater treatment sludge by Archaea-specific 16S rRNA gene
      sequencing analysis using Illumina sequencing technology. Phylotypes belonging to
      Euryarchaeota, including methanogens, were most abundant in all samples except
      for nitrogen-/phosphate-removing wastewater treatment sludge. High levels of Deep
      Sea Hydrothermal Vent Group 6 (DHVEG-6), WSA2, Terrestrial Miscellaneous
      Euryarchaeotal Group, and Miscellaneous Crenarchaeotic Group were also detected.
      Interestingly, DHVEG-6 was dominant in nitrogen-/phosphate-removing wastewater
      treatment sludge, indicating that unclear lineages of Archaea still exist in the
      anaerobic wastewater treatment sludges. These results reveal a previously unknown
      diversity of Archaea in sludge that can potentially be exploited for the
      development of more efficient wastewater treatment strategies. 

PMID- 25373333
TI  - Long-term outcomes of adjuvant radiotherapy after surgical resection of central
      neurocytoma.
AB  - BACKGROUND AND PURPOSE: The role of adjuvant radiotherapy for central
      neurocytomas (CNs) is not clear. Therefore, we aimed to examine the clinical
      outcomes of treating histologically confirmed CNs with adjuvant RT after surgical
      resection. MATERIAL AND METHODS: Sixty-three CN patients were retrospectively
      evaluated: 24 patients underwent gross total resection (GTR); 28, subtotal
      resection (STR); 9, partial resection (PR), and 2, biopsy (Bx). They underwent
      adjuvant RT after surgery (median dose, 54 Gy). RESULTS: The median follow-up was
      69 months (15-129 months). The 5-year overall survival (OS) and 5-year
      progression-free survival (PFS) were 94.4% and 95% after GTR + RT, 96.4% and 100%
      after STR + RT, and 100% and 90.9% after PR + RT. Only three patients had tumor
      recurrence: at the primary site at 30 and 24 months in two GTR + PR patients, and
      dissemination to the spinal cord at 75 months in one STR + RT patient. Thirty
      eight (63.3%) patients experienced late neurotoxicity (28, grade 1; 7, grade 2;
      3, grade 3). Short-term memory impairment was the most common toxicity.
      CONCLUSIONS: RT after incomplete resection (IR) led to OS and PFS comparable to
      those for GTR. Considering the excellent outcomes and limited late toxicity,
      adjuvant RT maybe a good option for CN patients who undergo IR.

PMID- 25373334
TI  - An improved 2b-RAD approach (I2b-RAD) offering genotyping tested by a rice (Oryza
      sativa L.) F2 population.
AB  - BACKGROUND: 2b-RAD (type IIB endonucleases restriction-site associated DNA)
      approach was invented by Wang in 2012 and proven as a simple and flexible method
      for genome-wide genotyping. However, there is still plenty of room for
      improvement for the existent 2b-RAD approach. Firstly, it doesn't include the
      samples pooling in library preparation as other reduced representation libraries.
      Secondly, the information of 2b-RAD tags, such as tags numbers and distributions,
      in most of species are unknown. The purposes of the research are to improve a new
      2b-RAD approach which possesses samples pooling, moreover to figure out the
      characteristic and application potentiality of 2b-RAD tags by bioinformatics
      analysis. RESULTS: Twelve adapter1 and an adapter2 were designed. A library
      approach comprising digestion, ligation, pooling, PCR and size selection were
      established. For saving costs, we used non-phosphorylated adapters and indexed
      PCR primers. A F2 population of rice (Oryza sativa .L) was genotyped to validate
      the new approach. On average, 2000332 high quality reads of each sample were
      obtained with high evenness. Totally 3598 markers containing 3804 SNPs were
      discovered and the missing rate was 18.9%. A genetic linkage map of 1385 markers
      was constructed and 92% of the markers' orders in the genetic map were in
      accordance with the orders in chromosomes. Meanwhile, the bioinformatics
      simulation in 20 species showed that the BsaXI had the most widespread
      recognition sites, indicating that 2b-RAD tags had a powerful application
      potentiality for high density genetic map. Using modified adapters with a fix
      base in 3'end, 2b-RAD was also fit for QTL studies with low costs. CONCLUSIONS:
      An improved 2b-RAD genotyping approach was established in this research and named
      as I2b-RAD. The method was a simple, fast, cost-effective and multiplex
      sequencing library approach. It could be adjusted by selecting different enzymes
      and adapters to fit for alternative uses including chromosomes assembly, QTL fine
      mapping and even natural population analysis.

PMID- 25373336
TI  - Effects of mouse utricle stromal tissues on hair cell induction from induced
      pluripotent stem cells.
AB  - BACKGROUND: Hair cells are important for maintaining our sense of hearing and
      balance. However, they are difficult to regenerate in mammals once they are lost.
      Clarification of the molecular mechanisms underlying inner ear disorders is also
      impeded by the anatomical limitation of experimental access to the human inner
      ear. Therefore, the generation of hair cells, possibly from induced pluripotent
      stem (iPS) cells, is important for regenerative therapy and studies of inner ear
      diseases. RESULTS: We generated hair cells from mouse iPS cells using an
      established stepwise induction protocol. First, iPS cells were differentiated
      into the ectodermal lineage by floating culture. Next, they were treated with
      basic fibroblast growth factor to induce otic progenitor cells. Finally, the
      cells were co-cultured with three kinds of mouse utricle tissues: stromal tissue,
      stromal tissue + sensory epithelium, and the extracellular matrix of stromal
      tissue. Hair cell-like cells were successfully generated from iPS cells using
      mouse utricle stromal tissues. However, no hair cell-like cells with hair bundle
      like structures were formed using other tissues. CONCLUSIONS: Hair cell-like
      cells were induced from mouse iPS cells using mouse utricle stromal tissues.
      Certain soluble factors from mouse utricle stromal cells might be important for
      induction of hair cells from iPS cells.

PMID- 25373337
TI  - Characteristics of hematopoietic stem cells of umbilical cord blood.
AB  - Umbilical cord blood collected from the postpartum placenta and cord is a rich
      source of hematopoietic stem cells (HSCs) and is an alternative to bone marrow
      transplantation. In this review we wanted to describe the differences (in
      phenotype, cytokine production, quantity and quality of cells) between stem cells
      from umbilical cord blood, bone marrow and peripheral blood. HSCs present in cord
      blood are more primitive than their counterparts in bone marrow or peripheral
      blood, and have several advantages including high proliferation. With using
      proper cytokine combination, HSCs can be effectively developed into different
      cell lines. This process is used in medicine, especially in hematology. 

PMID- 25373335
TI  - Genetic characterization of Greek population isolates reveals strong genetic
      drift at missense and trait-associated variants.
AB  - Isolated populations are emerging as a powerful study design in the search for
      low-frequency and rare variant associations with complex phenotypes. Here we
      genotype 2,296 samples from two isolated Greek populations, the Pomak villages
      (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS)
      in Crete. We compare their genomic characteristics to the general Greek
      population and establish them as genetic isolates. In the MANOLIS cohort, we
      observe an enrichment of missense variants among the variants that have drifted
      up in frequency by more than fivefold. In the Pomak cohort, we find novel
      associations at variants on chr11p15.4 showing large allele frequency increases
      (from 0.2% in the general Greek population to 4.6% in the isolate) with
      haematological traits, for example, with mean corpuscular volume (rs7116019,
      P=2.3 * 10(-26)). We replicate this association in a second set of Pomak samples
      (combined P=2.0 * 10(-36)). We demonstrate significant power gains in detecting
      medical trait associations. 

PMID- 25373339
TI  - Male-directed infanticide in spider monkeys (Ateles spp.).
AB  - Infanticide is considered a conspicuous expression of sexual conflict amongst
      mammals, including at least 35 primate species. Here we describe two suspected
      and one attempted case of intragroup infanticide in spider monkeys that augment
      five prior cases of observed or suspected infanticide in this genus. Contrary to
      the typical pattern of infanticide seen in most primate societies, where infants
      are killed by conspecifics independent of their sex, all eight cases of observed
      or suspected infanticide in spider monkeys have been directed toward male infants
      within their first weeks of life. Moreover, although data are still scant,
      infanticides seem to be perpetrated exclusively by adult males against infants
      from their own social groups and are not associated with male takeovers or a
      sudden rise in male dominance rank. Although the slow reproductive cycles of
      spider monkeys might favor the presence of infanticide because of the potential
      to shorten females' interbirth intervals, infanticide is nonetheless uncommon
      among spider monkeys, and patterns of male-directed infanticide are not yet
      understood. We suggest that given the potentially close genetic relationships
      among adult males within spider monkey groups, and the need for males to
      cooperate with one another in territorial interactions with other groups of
      related males, infanticide may be expected to occur primarily where the level of
      intragroup competition among males outweighs that of competition between social
      groups. Finally, we suggest that infanticide in spider monkeys may be more
      prevalent than previously thought, given that it may be difficult for observers
      to witness cases of infanticide or suspected infanticide that occur soon after
      birth in taxa that are characterized by high levels of fission-fusion dynamics.
      Early, undetected, male-biased infanticide could influence the composition of
      spider monkey groups and contribute to the female-biased adult sex ratios often
      reported for this genus. 

PMID- 25373338
TI  - Assessment of sperm damages during different stages of cryopreservation in water
      buffalo by fluorescent probes.
AB  - The present study was designed to investigate the sperm damages occurring in
      acrosome, plasma membrane, mitochondrial activity, and DNA of fresh, equilibrated
      and frozen-thawed buffalo semen by fluorescent probes. The stability of sperm
      acrosome and plasma membrane stability, mitochondrial activity and DNA status
      were assessed by fluorescein conjugated lectin Pisum sativum agglutinin, Annexin
      V/propidium iodide, JC-1 and TUNEL assay, respectively, under the fluorescent
      microscope. The damages percentage of acrosome integrity was significantly
      increased during equilibration and freezing-thawing process. The stability of
      sperm plasma membrane is dependent on stability of phosphatidylserine (PS) on the
      inner leaflet of plasma membrane. The frozen-thawed sperm showed externalization
      of PS leading to significant increase in apoptotic, early necrotic and necrotic
      changes and lowered high mitochondrial membrane potential as compared with the
      fresh sperm but all these parameters were not affected during equilibration.
      However, the DNA integrity was not affected during equilibration and freezing
      thawing procedure. In conclusion, the present study revealed that plasma membrane
      and mitochondria of buffalo sperm are more susceptible to damage during
      cryopreservation. Furthermore, the use of fluorescent probes to evaluate
      integrity of plasma and acrosome membranes, as well as mitochondrial membrane
      potential and DNA status increased the accuracy of semen analyses. 

PMID- 25373340
TI  - HTS for SMFS, organohalide respiration, new epigenetic mark, and a decoy
      receptor.
AB  - Each month, Chemistry & Biology Select highlights a selection of research reports
      from the recent literature. These highlights are a snapshot of interesting
      research done across the field of chemical biology. This month's Select
      highlights an on-chip platform for high-throughput force microscopy, a structural
      view of organohalide respiration, evidence that 5-hydroxymethylcytosine is an
      epigenetic mark, and use of a decoy receptor to thwart oncogene signaling. 

PMID- 25373341
TI  - ACP-AasS you like it.
AB  - Acyl carrier proteins (ACPs) are promiscuous small proteins that play essential
      roles in the biosynthesis of many natural products, but our understanding of how
      they interact with various enzymes within larger protein complexes is lacking. In
      this issue of Chemistry and Biology, Beld and coworkers describe an enzymatic
      labeling method that will allow tracking of ACPs as they interact with their
      partners both in vitro and vivo.

PMID- 25373342
TI  - Enzyme dynamics and engineering: one step at a time.
AB  - Although protein dynamics are accepted as being essential for enzyme function,
      their effects are not fully understood. In this issue of Chemistry and Biology,
      Gobeil and coworkers describe how engineered changes in the millisecond motions
      of a mutant TEM-1 beta-lactamase do not significantly affect substrate turnover.
      This mutational robustness has implications for protein engineering and design
      strategies. 

PMID- 25373343
TI  - Molecular insights into how ligands activate or inactivate LasR.
AB  - The article by Gerdt and colleagues in this issue of Chemistry & Biology provides
      molecular insights into how nonlactone quorum sensing modulators either activate
      or deactivate LasR. Interestingly, an antagonist could flip into an agaonist upon
      mutation of a single residue in the autoinducer binding site. 

PMID- 25373347
TI  - Erratum to: Maternal exposure to fine particulate matter (PM2.5) and pregnancy
      outcomes: a meta-analysis.

PMID- 25373346
TI  - Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway.
AB  - Mammalian sterile 20-like 1 (Mst1), an upstream serine/threonine-specific protein
      kinase of the Hippo pathway, is reported to play important roles in tumor
      suppression and organ size regulation in mammals via regulating cell
      proliferation and survival. However, whether it is involved in the pathogenesis
      of malignant gliomas remains poorly understood. Therefore, in the present work,
      we examined the effect and mechanism of Mst1 on the proliferation and apoptosis
      of malignant glioma cells. The cell proliferation and growth of glioma cells were
      examined by EdU incorporation and CCK-8 assay. In addition, the cell apoptosis
      was assessed by flow cytometry. We found that down-regulation of Mst1 promoted
      glioma cell proliferation and growth, but inhibited the cell apoptosis.
      Consistent with this, over-expression of Mst1 inhibited glioma cell proliferation
      and growth. Interestingly, Mst1 did not affect the phosphorylation of YAP1, the
      key downstream molecule of Hippo pathway. However, Mst1 was found to bind to AKT
      in glioma cell and negatively regulated AKT and mTOR activity. Finally, the
      increased cell proliferation rate induced by Mst1 down-regulation was partially
      abolished by down-regulation of AKT1. Meanwhile, glioma cell growth inhibition
      induced by Mst1 over-expression was partially rescued by over-expression of AKT1.
      Taken together, these findings suggest that Mst1 regulates proliferation of
      glioma cells via AKT/mTOR signaling pathway. 

PMID- 25373349
TI  - Ingenol derivates promising for HIV eradication.
AB  - The eradication of HIV is at this moment one of the greatest challenges in the
      fight against HIV/AIDS. Despite the prolonged effectiveness of current anti-HIV
      therapies, capable of keeping patients with undetectable viremia for long periods
      of time, HIV-infected patients cannot be cured due to the establishment of HIV
      latent reservoirs. Therefore, several therapeutic strategies are being evaluated
      to eliminate these viral reservoirs. One of these strategies, termed "shock and
      kill", aims to attack the latent reservoir by simultaneous treatment with HIV
      activating agents to stimulate viral replication in latently infected cells and
      antiretroviral therapy to block new infections. A number of compounds have been
      suggested for the shock and kill strategy including histone deacetylase
      inhibitors (HDACI), histone methyltransferases (HMT), DNA methyltransferase
      inhibitors (DNMTI), and protein kinase C (PKC) activators.

PMID- 25373348
TI  - Characterisation of patients with Glanzmann thrombasthenia and identification of
      17 novel mutations.
AB  - Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder
      characterised by quantitative and/or qualitative defects of the platelet
      glycoprotein (GP) IIb/IIIa complex, also called integrin alphaIIbbeta3.
      alphaIIbbeta3 is well known as a platelet fibrinogen receptor and mediates
      platelet aggregation, firm adhesion, and spreading. This study describes the
      molecular genetic analyses of 19 patients with GT who were diagnosed on the basis
      of clinical parameters and platelet analyses. The patients' bleeding signs
      include epistaxis, mucocutaneous bleeding, haematomas, petechiae,
      gastrointestinal bleeding, and menorrhagia. Homozygous or compound heterozygous
      mutations in ITGA2B or ITGB3 were identified as causing GT by sequencing of
      genomic DNA. All exons including exon/intron boundaries of both genes were
      analysed. In a patient with an intronic mutation, splicing of mRNA was analysed
      using reverse transcriptase (RT)-PCR of platelet-derived RNA. In short, 16 of 19
      patients revealed 27 different mutations (ITGA2B: n=17, ITGB3: n=10). Seventeen
      of these mutations have not been published to date. Mutations in ITGA2B or ITGB3
      were identified as causing GT in 16 patients. We detected a total of 27 mutations
      in ITGA2B and ITGB3 including 17 novel missense, nonsense, frameshift and splice
      site mutations. In addition, three patients revealed no molecular genetic
      anomalies in ITGA2B or ITGB3 that could explain the suspected diagnosis of GT. We
      assume that these patients may harbour defects in a regulatory element affecting
      the transcription of these genes, or other proteins may exist that are important
      for activating the alphaIIbbeta3 complex that may be affected. 

PMID- 25373350
TI  - RNA viruses at the forefront of human infections - HIV, hepatitis C, and now
      Ebola.
AB  - AIDS emerged in 1981, breaking a period of proud medical progresses in
      controlling infectious diseases with antimicrobials and vaccines. In an
      unprecedented way, HIV has attracted much attention for three decades, driving
      the discovery of new extraordinary molecular diagnostic tools and antiviral
      drugs. As a result, advances in antiretroviral therapy have made it possible to
      change HIV infection into a chronic illness. However, the prospects for HIV
      eradication in the short term are not envisioned for the more than 35 million
      people worldwide estimated to be living with HIV. 

PMID- 25373351
TI  - Hemorrhagic Transformation of Scrub Typhus Encephalitis: A Rare Entity.
AB  - Central nervous system (CNS) involvement of scrub typhus infection is well known.
      Most CNS involvement of scrub typhus infection present as meningitis or
      encephalitis. We report on a patient suffering from hemorrhagic transformation of
      intracranial lesions caused by Orientia tsutsugamushi. A 53-year-old female
      farmer who was infected by scrub typhus was treated with doxycycline and
      recovered from the systemic illness. However, headache persisted. Brain
      radiologic studies revealed acute intracranial hemorrhage and enhancing lesion,
      which implied a CNS involvement. Hemorrhagic transformation of encephalitis by
      scrub typhus is very rare complication and to our best knowledge, this is the
      first report of hemorrhagic transformation of scrub typhus encephalitis.
      Clinician should consider the possibility of hemorrhagic transformation of
      encephalitis in cases of scrub typhus infection. 

PMID- 25373357
TI  - Relationships between the antidotal efficacy and structure, PK/PD parameters and
      bio-relevant molecular descriptors of AChE reactivating oximes: inclusion and
      integration to biopharmaceutical classification systems.
AB  - INTRODUCTION: The therapeutic outcome of oximes used as reactivators of
      phosphorylated human acetylcholinesterase (AChE) is influenced, among other
      factors, by their biological distribution, their in vivo ability to achieve the
      nucleophilic attack and their affinity for the anionic center of the
      intact/inhibited AChE. AREAS COVERED: An in silico evaluation of the molecular
      descriptors and biopharmaceutical properties of 454 set of oximes has been
      achieved. The available pharmacokinetic (PK) data was analyzed, in an attempt to
      illustrate their common characteristics and particularities. Based on the
      observed high water solubility and low permeability across biological barriers,
      we applied the officially adopted classification systems based on
      biopharmaceutical properties to identify the existing biopharmaceutical
      differences between the various oxime entities and to predict their in vivo fate.
      EXPERT OPINION: The structural differences of the organophosphorus compounds (OP)
      and the available oximes reactivators of OP-inhibited AChE generate distinct
      toxicokinetic or PK profiles. The tissue compartment specific distribution is one
      of the key elements for assessment of reactivating efficiency. The distribution
      through highly specialized barriers, such as blood-brain barrier remains a
      considerable challenge. The high solubility - low permeability biopharmaceutical
      profile of oximes can be used to suggest the possible involvement of active
      transport systems.

PMID- 25373358
TI  - Characteristics of clinical trial websites: information distribution between
      ClinicalTrials.gov and 13 primary registries in the WHO registry network.
AB  - BACKGROUND: It is well known that information about clinical trials is not easily
      accessible by the public. In Japan, clinical trial information can be accessed by
      the general public through online registries; however, many people find these
      registries difficult to use. To improve current clinical trial registries, we
      propose that combining them with clinical information phrased in lay terms would
      be beneficial to other interested professionals such as journalists and
      clinicians, as well as the general public. Therefore, this study aimed to examine
      the current pattern of distribution of clinical trial information from the
      primary World Health Organization (WHO) registries. Based on the results of this
      assessment, we then aimed to build and evaluate a prototype of the Japan Primary
      Registries Network (JPRN) portal that would be easily accessible to patients and
      the public, while still remaining useful for professionals. METHODS: We assessed
      a total of 14 primary clinical trial registries listed on the WHO International
      Clinical Trials Registry Platform between January and February 2013. Website
      content was accessed and checked against a series of items that looked at
      usability, communication, design and accessibility of the sites. We excluded
      registries that were not active or were not on the approved WHO registry list at
      the time of our assessment. We also examined only the English versions of the
      websites as native-language registries may offer more functionality or different
      content than the English version of the same website. RESULTS: All registries
      examined had a function allowing users to search the registry data and that
      displayed the related information from the search, including the clinical trial
      registration data. However, few websites were found to be user-friendly, and
      there was little integration with social media. CONCLUSIONS: We confirmed that
      there are few websites providing useful clinical trial information to patients
      and their families. However, information gleaned from some of the more advanced
      online registries could be used to improve the content and functionality of the
      JPRN portal.

PMID- 25373359
TI  - Renal sympathetic denervation for resistant hypertension: a transiently sustained
      placebo effect?

PMID- 25373361
TI  - Evaluation of the optimum time for direct application of fibroblast growth factor
      to human traumatic tympanic membrane perforations.
AB  - OBJECTIVE: The aim of this study was to determine the optimum time for direct
      application of basic fibroblast growth factor (bFGF) on large traumatic tympanic
      membrane perforations (TMPs). STUDY DESIGN: Prospective clinical study. SETTING:
      Tertiary University Hospital. METHODS: Ninety-three patients, with traumatic TMPs
      greater in extent than 25% of the entire tympanic membrane, were randomized into
      observation and bFGF-treated groups (~0.2-0.25 mL of bFGF solution was applied
      directly onto the TM once daily and continued until the perforation closed).
      Initial visit times were subcategorized into perforation durations of <=3 and >3
      days, thereby rendering two subgroups, as follows: A and B in the observation
      group; and C and D in the bFGF-treated group. The closure rate and mean closure
      time were evaluated after 6 months. RESULTS: Eighty-six patients were finally
      analyzed. After 6 months, the bFGF-treated group exhibited a significantly higher
      total closure rate (97.8 versus 82.5%, p < 0.05) and a shorter mean closure time
      (12.5 +/- 3.4 versus 34.0 +/- 5.9 days, p < 0.05) compared with the spontaneous
      healing group. In addition, in the observation group, visiting time was not
      associated with differences in closure rate (p > 0.05) and mean closure time (p >
      0.05), between the A and B subgroups. Similarly, in the bFGF-treated group,
      visiting time was not associated with differences in closure rate (p > 0.05)
      between the C and D subgroups. However, the D subgroup was characterized by
      significantly shortened mean closure time compared with the C subgroup (p <
      0.05). CONCLUSIONS: This study shows the beneficial effect of bFGF on human
      traumatic large TMPs when applied after the 3rd day post-injury had passed (i.e.
      during the proliferative stage of wound healing). The procedure can not only
      significantly shorten closure time but can also reduce both the clinical
      administration duration and occurrence of side-effects associated with bFGF.

PMID- 25373360
TI  - Antihypertensive treatment and control according to gender, education, country of
      birth and psychiatric disorder: the Swedish Primary Care Cardiovascular Database
      (SPCCD).
AB  - The reasons why women and men are treated with different antihypertensive drugs
      are not clear. Whether socioeconomic factors influence prescription patterns and
      blood pressure control differently in women and men has not been investigated.
      This cross-sectional study performed in a cohort of hypertensive patients from
      the Swedish Primary Care Cardiovascular Database (SPCCD) examined the influence
      of educational level, country of birth, gender and concomitant psychiatric
      disorder on prescription pattern and blood pressure control in 40,825
      hypertensive patients. Men were more often than women treated with calcium
      channel blocker and angiotensin-converting enzyme inhibitor (ACEI), irrespective
      of education, country of birth and psychiatric disorder. Educational level
      influenced the prescription pattern to some extent, where the gender differences
      were reduced in patients with a higher educational level. In women, but not in
      men, high educational level and concomitant psychiatric disorder were associated
      with a higher proportion reaching target blood pressure. The predominant use of
      ACEI and calcium channel blockers in men is not influenced by educational level,
      country of birth or psychiatric disorder. Thus other explanations must be
      considered such as gender differences in side effects. Educational level seems to
      have a greater impact on reaching target blood pressure in women compared with
      men.

PMID- 25373362
TI  - Incidence and prognostic significance of positive peritoneal lavage in colorectal
      cancer.
AB  - PURPOSE: The significance of peritoneal lavage cytology as a prognostic marker
      has been examined in various types of cancer. However, the meaning of positive
      peritoneal lavage cytology in colorectal cancer is still controversial. The aim
      of this review is to evaluate the prognostic significance of positive peritoneal
      lavage cytology in colorectal cancer. METHODS: An English literature search was
      performed on all studies published between 1998 and 2014 that compared the
      detection of peritoneal free cancer cells with survival or recurrence. RESULTS:
      Eighteen articles met the inclusion criteria. All studies employed one (or more)
      of the three techniques used to detect free cancer cells in the peritoneal
      cavity: (1) conventional cytology, (2) immunocytochemistry or (3) polymerase
      chain reaction. The incidence of positive peritoneal lavage cytology ranged from
      2.2 to 47.2% across the studies. The factors correlated with positive peritoneal
      lavage cytology were tumor penetration and metastases (lymph node, liver and
      peritoneum). In nine studies, positive lavage findings were associated with a
      worse survival, and it was associated with increased recurrence in 13 studies.
      CONCLUSION: Positive peritoneal lavage cytology seems to be an indicator of a
      poor prognosis in colorectal cancer patients. Further studies are needed to
      clarify the prognostic impact of peritoneal lavage cytology, by comparing the
      different methods used for the collection of the peritoneal lavage.

PMID- 25373363
TI  - Acute graft-versus-host disease following simultaneous pancreas-kidney
      transplantation: report of a case.
AB  - Acute graft-versus-host-disease (aGVHD) is a rare complication in the setting of
      pancreas-kidney transplantation (PKT). We herein describe the case of a 37-year
      old male with severe type 1 diabetes with chronic renal failure who received
      simultaneous PKT from a female donor. Diarrhea developed on postoperative day
      (POD) 10. Subsequently, fever and liver dysfunction occurred on POD 32. Skin
      rashes appeared with pain and itching on his trunk and extremities on POD 40. As
      pancytopenia occurred on POD 63, bone marrow biopsies demonstrated profound
      hypoplastic marrow. On POD 69, we eventually made a definitive diagnosis of aGVHD
      because skin biopsies revealed the XX chromosome signal in a fluorescence in situ
      hybridization analysis. Thereafter, 100 mg of prednisolone was administered for 5
      days. Although every symptom was temporarily improved, on POD 156, the patient
      expired from the septic pneumonia without any effects of antibiotics. Clinician
      should be aware that PKT has the potential to induce aGVHD. 

PMID- 25373365
TI  - Breast-feeding and hospitalization for asthma in early childhood: a nationwide
      longitudinal survey in Japan.
AB  - OBJECTIVE: Whether or not breast-feeding is protective against asthma among
      children is still controversial. Therefore, we examined the effects of breast
      feeding on hospitalization for asthma in early childhood. DESIGN: Secondary data
      analyses of a nationwide longitudinal survey of children in Japan ongoing since
      2001, with results collected from 2001 to 2004. We used logistic regression
      models to evaluate the associations of breast-feeding with hospitalization for
      asthma in children between the ages of 6 and 42 months, adjusting for children's
      factors (sex, day-care attendance and presence of older siblings) and maternal
      factors (educational attainment and smoking habit). Setting All over Japan.
      SUBJECTS: Term singleton children with information on feeding practices during
      infancy (n 43367). RESULTS: After adjusting for maternal factors and children's
      factors, exclusive breast-feeding at 6-7 months of age was associated with
      decreased risk of hospitalization for asthma in children. The adjusted odds ratio
      was 0.77 (95% CI 0.56, 1.06). One-month longer duration of breast-feeding was
      associated with a 4% decreased risk of hospitalization for asthma (OR = 0.96; 95%
      CI 0.92, 0.99). CONCLUSIONS: The protective effects of breast-feeding on
      hospitalization for asthma were observed in children between the ages of 6 and 42
      months.

PMID- 25373364
TI  - Non-secreting benign glucagonoma diagnosed incidentally in a patient with
      refractory thrombocytopenic thrombotic purpura: report of a case.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder, which
      may be idiopathic or secondary to a variety of diseases. However, there are very
      few reports of TTP in the context of pancreatic neoplasms. We report a case of
      relapsing TTP after initial treatment with plasmapheresis, corticosteroids, and
      rituximab, in a 59-year-old woman. During diagnostic work-up, a pancreatic lesion
      35 * 25 mm in size was discovered incidentally and splenopancreatectomy was
      performed. The pathological diagnosis was benign glucagonoma. The hematological
      symptoms resolved completely after the procedure and 3 years later, the patient
      is well with no sign of recurrence of TTP or glucagonoma. To our knowledge, this
      represents the first documented case of a non-secreting benign pancreatic
      neuroendocrine tumor (glucagonoma) associated with TTP that is refractory to
      standard treatment.

PMID- 25373366
TI  - Interventions for women in subsequent pregnancies following obstetric anal
      sphincter injury to reduce the risk of recurrent injury and associated harms.
AB  - BACKGROUND: Perineal damage occurs frequently during childbirth, with severe
      damage involving injury to the anal sphincter reported in up to 18% of vaginal
      births. Women who have sustained anal sphincter damage are more likely to suffer
      perineal pain, dyspareunia (painful sexual intercourse), defaecatory dysfunction,
      and urinary and faecal incontinence compared to those without damage.
      Interventions in a subsequent pregnancy may be beneficial in reducing the risk of
      further severe trauma and may reduce the risk of associated morbidities.
      OBJECTIVES: To examine the effects of Interventions for women in subsequent
      pregnancies following obstetric anal sphincter injury for improving health.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 September 2014). SELECTION CRITERIA: Randomised controlled trials,
      cluster-randomised trials and multi-arm trials assessing the effects of any
      intervention in subsequent pregnancies following obstetric anal sphincter injury
      to improve health. Quasi-randomised controlled trials and cross-over trials were
      not eligible for inclusion. DATA COLLECTION AND ANALYSIS: No trials were
      included. In future updates of this review, at least two review authors will
      extract data and assess the risk of bias of included studies. MAIN RESULTS: No
      eligible completed trials were identified. One ongoing trial was identified.
      AUTHORS' CONCLUSIONS: No relevant trials were included. The effectiveness of
      interventions for women in subsequent pregnancies following obstetric anal
      sphincter injury for improving health is therefore unknown. Randomised trials to
      assess the relative effects of interventions are required before clear practice
      recommendations can be made.

PMID- 25373367
TI  - Usefulness of a real-time bowel sound analysis system in patients with severe
      sepsis (pilot study).
AB  - Healthy bowel function is an important factor when judging the advisability of
      early enteral nutrition in critically ill patients, but long-term observation and
      objective evaluation of gastrointestinal motility are difficult. In the study,
      real-time continuous measurement of gastrointestinal motility was performed in
      patients with severe sepsis using a developed bowel sound analysis system, and
      the correlation between bowel sounds and changes over time in blood
      concentrations of interleukin (IL)-6, which is associated with sepsis severity,
      was evaluated. The subjects were five adult patients in the acute phase of severe
      sepsis on a mechanical ventilator, with IL-6 blood concentrations >=100 pg/mL,
      who had consented to participate in the study. Gastrointestinal motility was
      measured for a total of 62,399 min: 31,544 min in 3 subjects in the no-steroids
      group and 30,855 min in 2 subjects in the steroid treatment group. In the no
      steroids group, the bowel sound counts were negatively correlated with IL-6 blood
      concentration, suggesting that gastrointestinal motility was suppressed as IL-6
      blood concentration increased. However, in the steroid treatment group,
      gastrointestinal motility showed no correlation with IL-6 blood concentration (r
      = -0.25, p = 0.27). The IL-6 blood concentration appears to have decreased with
      steroid treatment irrespective of changes in the state of sepsis, whereas bowel
      sound counts with the monitoring system reflected the changes in the state of
      sepsis, resulting in no correlation. This monitoring system provides a useful
      method of continuously, quantitatively, and non-invasively evaluating
      gastrointestinal motility in patients with severe sepsis. Gastrointestinal
      motility might be useful as a parameter reflecting disease severity, particularly
      in patients treated with steroids. 

PMID- 25373369
TI  - [What is the optimal treatment for rectal cancer?].

PMID- 25373368
TI  - A novel small animal extracorporeal circulation model for studying
      pathophysiology of cardiopulmonary bypass.
AB  - Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Despite
      the fact that ECCcauses damage to blood components and is non-physiologic, its
      pathophysiology has not been fully elucidated. This is because difficulty in
      clinical research and animal experiments keeps the knowledge insufficient.
      Therefore, it is desirable to have a miniature ECC model for small animals, which
      enables repetitive experiments, to study the mechanism of pathophysiological
      changes during ECC. We developed a miniature ECC system and applied it to the
      rat. We measured changes in hemodynamics, blood gases and hemoglobin (Hb)
      concentration, serum cytokines (TNF-alpha, IL-6, IL-10), biochemical markers
      (LDH, AST, ALT), and the wet-to-dry weight (W/D) ratio of the lung for assessing
      whether the rat ECC model is comparable to the human ECC. The ECC system
      consisted of a membranous oxygenator (polypropylene, 0.03 m(2)), tubing line
      (polyvinyl chloride), and roller pump. Priming volume of this system is only 8
      ml. Rats (400-450 g) were divided into the SHAM group (n = 7) and the ECC group
      (n = 7). Blood samples were collected before, 60 and 120 min after initiation of
      ECC. During ECC, blood pressure and Hb were maintained around 80 mmHg and 10
      g/dL, respectively. The levels of the inflammatory and biochemical markers and
      the W/D ratio were significantly elevated in the ECC group, indicating some organ
      damages and systemic inflammatory responses during ECC. We successfully
      established the ECC for the rat. This miniature ECC model could be a useful
      approach for studying the mechanism of pathophysiology during ECC and basic
      assessment of the ECC devices.

PMID- 25373370
TI  - [Endoscopic treatment for rectal cancer].

PMID- 25373371
TI  - [Minimally invasive surgery for rectal cancer].

PMID- 25373372
TI  - [Treatment for locally recurrent rectal cancer].

PMID- 25373373
TI  - [Relationship between visceral fat and development of colorectal neoplasms using
      computed tomographic colonography and adipocytokine levels].
AB  - We evaluated the relationship between colorectal neoplasms and visceral obesity
      using computed tomographic colonography and adipocytokine levels. We included 123
      patients and classified them into four groups as per computed tomographic
      colonography: no lesion (NL; n=40), adenomatous polyp (polyp; n=41), early
      colorectal cancer (eCRC; n=21), and advanced CRC (aCRC; n=21). We also measured
      the patients' serum metabolic markers and adipocytokine levels. The visceral
      adiposity index in the polyp and eCRC groups was significantly higher than that
      in the NL group. Visceral obesity is an important risk factor for the development
      of colonic polyps. Computed tomographic colonography could be a useful
      examination technique not only for diagnosis of colorectal neoplasms but also for
      simultaneous evaluation of visceral obesity. 

PMID- 25373374
TI  - [A case of advanced gastric cancer with tumor embolus in the portal vein and
      liver metastasis responding to S-1 plus cisplatin chemotherapy].
AB  - A 67-year-old woman presented with anemia. Computed tomography and upper
      gastrointestinal endoscopy revealed a primary gastric cancer with tumor embolus
      in the portal vein, liver metastasis, lymph node metastasis, and pancreatic
      involvement. Because curative surgery was deemed impossible, we started
      chemotherapy using S-1 (120 mg/m(2)/day for 3 weeks, followed by discontinuation
      for 2 weeks) plus cisplatin (80 mg/m(2)/day on days 1 and 8). After 4 courses of
      chemotherapy, the tumor embolus in the portal vein, liver metastasis, lymph node
      metastasis, and pancreatic involvement had resolved. Therefore, we performed
      distal gastrectomy. Histological examination revealed ypT1a, ly0, v0, ypN0
      (0/49), ypCY0, ypStage IA, with a two-grade histological change in the main tumor
      after chemotherapy. Postoperatively, she underwent adjuvant chemotherapy with S-1
      for 1 year (120 mg/m(2)/day for 4 weeks, followed by discontinuation for 2
      weeks). At the 30-month follow-up after the adjuvant chemotherapy, she had no
      recurrence. 

PMID- 25373375
TI  - [A case of Lynch syndrome with advanced jejunal cancer].
AB  - A woman in her 80s had two episodes of ileus, which led to the diagnosis of
      advanced jejunal cancer. She was diagnosed with Lynch syndrome when she was in
      her 60s, for which she underwent annual follow-up with computed tomography for 8
      years. Unfortunately, she died from the recurrence of jejunal cancer and liver
      metastases. Jejunal cancer is relatively rare in Lynch syndrome, and no
      surveillance strategy has been established for small bowel cancer. In patients
      with unexplained abdominal complaints, small bowel cancer should be considered. 

PMID- 25373376
TI  - [A case of invasive micropapillary carcinoma of the pancreas concomitant with
      intraductal papillary mucinous neoplasm].
AB  - Invasive micropapillary carcinoma (IMPC), a rare subtype of adenocarcinoma, has a
      high incidence of lymph node metastasis and is associated with a poor prognosis.
      A 77-year-old woman was admitted to our hospital for the assessment of
      intraductal papillary mucinous neoplasm (IPMN). We diagnosed her with pancreatic
      cancer concomitant with IPMN and performed pancreaticoduodenectomy. The lesion
      was predominantly composed of ductal adenocarcinoma with a micropapillary
      component. On immunohistochemical analysis, a characteristic " inside-out
      pattern" was observed in the micropapillary component. This confirmed the
      diagnosis of pancreatic cancer with a micropapillary component. In the present
      report, we describe a very rare case of IMPC of the pancreas. 

PMID- 25373377
TI  - [FOLFIRINOX-induced hyperammonemic encephalopathy in a patient with pancreatic
      cancer].
AB  - Hyperammonemic encephalopathy is a rare adverse event of chemotherapies based on
      high-dose 5-fluorouracil. We present a woman in her 70s with metastatic
      pancreatic adenocarcinoma who underwent FOLFIRINOX therapy. She developed acute
      onset disturbance of consciousness after completing the first 5-fluorouracil
      infusion cycle (2400 mg/m(2)/46h). We suspected hyperammonemic encephalopathy
      induced by 5-fluorouracil and administered branched-chain amino acids solutions
      and she recovered within a few hours of treatment. Brain computed tomography and
      magnetic resonance imaging revealed no abnormal findings. She subsequently
      received chemotherapy with gemcitabine and developed no further hyperammonemia.
      To the best of our knowledge, this is the first report of FOLFIRINOX-induced
      hyperammonemic encephalopathy in a patient with pancreatic cancer. 

PMID- 25373378
TI  - [A case of hypercalcemia associated with parathyroid hormone-related protein
      produced by the recurrence of B-cell lymphoma of the pancreas].
AB  - An 87-year-old woman was diagnosed with primary diffuse large B-cell lymphoma of
      the pancreas by endoscopic ultrasonography-guided fine needle aspiration.
      Complete remission was achieved after treatment with six courses of R-CHOP
      chemotherapy. However, two and a half years later, she was readmitted because of
      weakness during walking. At this time, laboratory tests revealed hypercalcemia
      associated with high plasma levels of parathyroid hormone-related protein
      (PTHrP), but bone lesions were not detected. Although computed tomography only
      revealed splenomegaly, we suspected a recurrence of her malignant lymphoma
      because she also had marked elevation of soluble interleukin-2 receptor and
      lactate dehydrogenase levels. Bone marrow examination revealed the involvement of
      Burkitt's lymphoma cells with malignant transformation. Immunohistochemical
      analysis confirmed that hypercalcemia was caused by a paraneoplastic syndrome
      related to PTHrP-producing B-cell lymphoma cells. Unfortunately, the patient's
      general condition rapidly deteriorated, and she died soon after admission. Our
      case is unusual because of the presentation of bone marrow relapse of malignant
      lymphoma. 

PMID- 25373379
TI  - [A case of arteriovenous malformation of the pancreas treated with n-butyl-2
      cyanoacrylate transcatheter arterial embolization].
AB  - A 49-year-old man was admitted to our hospital complaining of severe epigastric
      pain. Contrast-enhanced abdominal computed tomography revealed an arteriovenous
      malformation of the pancreatic uncus. Because of unbearable epigastric pain,
      transcatheter arterial embolization was performed with n-butyl-2-cyanoacrylate.
      Subsequently, his symptoms fully resolved; no recurrence of the arteriovenous
      malformation was seen more than 1 year after the embolization. 

PMID- 25373380
TI  - [A case of definitive type 2 autoimmune pancreatitis diagnosed using endoscopic
      ultrasound-guided fine needle aspiration biopsy].
AB  - A 29-year-old man with ulcerative colitis presented to the hospital complaining
      of persistent back pain. Pancreatic enzymes and tumor markers were elevated;
      imaging showed diffuse narrowing of the main pancreatic duct associated with
      diffuse pancreatic enlargement. We therefore performed an endoscopic ultrasound
      guided fine needle aspiration (EUS-FNA) biopsy of the pancreas using a 19-gauge
      needle. Histopathology revealed interlobular fibrosis, neutrophil infiltration in
      the intralobular ducts and acini, and very few immunoglobulin G4-positive cells.
      The patient was diagnosed with type 2 autoimmune pancreatitis and started on oral
      steroids; subsequently, we observed an improvement in the pancreatic enlargement
      and duct narrowing. Histologically proven type 2 autoimmune pancreatitis is rare
      in Japan. 

PMID- 25373381
TI  - Assessing parental empathy: a role for empathy in child attachment.
AB  - Although empathy has been associated with helping behavior and relationship
      quality, little research has evaluated the role of parental empathy in the
      development of parent-child relationships. The current study (1) establishes
      preliminary validity of the Parental Affective and Cognitive Empathy Scale
      (PACES), a method for coding empathy from parents' narrative responses to the
      Parent Development Interview - Revised for School-Aged Children (PDI-R-SC), and
      (2) tests a theoretical model of empathy and attachment. Sixty caregivers and
      their children completed a battery of questionnaire and interview measures,
      including the PDI-R-SC and the Child Attachment Interview (CAI). Caregivers'
      interview narratives were scored for empathy using PACES. PACES showed good
      interrater reliability and good convergent validity with a self-report empathy
      measure. Parent empathy was positively related to child attachment security
      (using a continuous score for narrative coherence) and emotional openness on the
      CAI, as well as to child perceptions of parental warmth. Moreover, parent empathy
      mediated the relation between parents' self-reported attachment style and their
      children's attachment security. Implications for attachment theory and future
      directions for establishing scale validity are discussed. 

PMID- 25373382
TI  - Analyses of drugs stored at home by elderly patients with chronic heart failure.
AB  - BACKGROUND: Evidence-based pharmacotherapy improves morbidity and mortality in
      patients with chronic heart failure (CHF). Medication adherence management is
      important for the effectiveness and safety of treatment. This study investigated
      drugs stored at home by elderly CHF patients. METHODS AND RESULTS: One hundred
      and one patients with stable CHF age >=65 years were visited at home where a
      standardized interview and a thorough assessment of medication were performed.
      Mean age of the patients was 77.7 +/- 6.1 years, 53 % male, mean NYHA functional
      class of 2.8 +/- 0.7 and a Minnesota-Living-with-Heart-Failure score of 59.4 +/-
      28.6 points indicating reduced quality of life. The mean number of different drug
      packs per patient was 13.1 +/- 5.5, corresponding to a mean indexed value per
      patient of <euro>403 +/- 48. Cardiovascular drugs accounted for 32 % of the
      packs. On average, 2.4 +/- 3.2 packs contained medication that was not taken by
      the patient (18 % of the medication, mean indexed value <euro>61 +/- 8). Fifty
      six percent of the unused drugs were prescribed by general practitioners, 23 % in
      the hospital, and 7 % by medical specialists and 14 % were over-the-counter
      drugs. Sixty-three packages (5 %) of the drugs at home were expired (mean indexed
      value per patient <euro>12 +/- 3). CONCLUSION: On average, elderly patients with
      CHF have to manage 13 different drug packs per day at home of which a significant
      portion is not taken as prescribed. New strategies are needed to support
      medicines management at home.

PMID- 25373383
TI  - Cheyne-Stokes respiration in heart failure: friend or foe? Hemodynamic effects of
      hyperventilation in heart failure patients and healthy volunteers.
AB  - OBJECTIVE: In patients with heart failure (HF), Cheyne-Stokes respiration (CSR)
      is characterized by chronic hyperventilation (HV) with low arterial partial
      pressure of carbon dioxide (pCO2). It is still unclear whether this HV represents
      a compensatory response to HF or an independent comorbidity. This study
      investigated the hemodynamic effects of HV in HF patients and volunteers.
      METHODS: A total of 15 volunteers [13 male, 25 +/- 4 years, brain natriuretic
      peptide (BNP) <49 pg/mL, left ventricular rejection fraction (LVEF) >55 %) and 20
      HF patients with reduced LVEF (15 male, 67.7 +/- 12 years, NYHA class 2.6 +/-
      0.6, BNP 790 +/- 818 pg/mL, LVEF 32.4 +/- 7.3 %) were enrolled. Hemodynamics was
      monitored noninvasively in volunteers (TaskForce Monitor, CNSystems) and
      invasively in HF patients. RESULTS: During HV, the transcutaneous CO2 pressure in
      volunteers decreased from 38.7 +/- 2.5 to 28.6 +/- 3.3 mmHg (p < 0.001) and pCO2
      in HF patients decreased from 33.6 +/- 3.7 to 22.2 +/- 3.2 mmHg (p < 0.001).
      There was a significant increase in cardiac output (CO) in both volunteers (6.2
      +/- 1.3-7.5 +/- 1.3 L/min, p < 0.001) and HF patients (4.4 +/- 1.3-5.0 +/- 1.3
      L/min), mainly as a result of an increase in heart rate (67.4 +/- 7.6-82.8 +/-
      10.9/min, p < 0.001; and 77.2 +/- 17.7-86.2 +/- 22.4/min, p < 0.001,
      respectively); stroke volume (SV) was unchanged in volunteers (93.7 +/- 19.6-93.8
      +/- 21.4 mL) and only slightly increased in HF patients (64.4 +/- 28.7-68.5 +/-
      23.2 mL). CONCLUSIONS: CSR with associated HV may be a compensatory mechanism in
      patients with a failing heart. This compensatory mechanism includes an increase
      in heart rate, which might be deleterious in the long run.

PMID- 25373384
TI  - Gender aspects in clinical presentation and prognostication of chronic heart
      failure according to NT-proBNP and the Heart Failure Survival Score.
AB  - AIMS: We performed a prospective multi-center study to assess gender-specific
      differences in the predictive value of the measured level of NT-proBNP and the
      calculated Heart Failure Survival Score (HFSS). METHODS: Baseline characteristics
      and follow-up data up to 5 years from 2,019 men and 530 women diagnosed with
      chronic heart failure (CHF) due to ischemic heart disease or dilated
      cardiomyopathy were prospectively compared. Death from any cause constituted the
      endpoint of the study. NT-proBNP was measured and HFSS calculated according to
      standard methods. Survival of men and women according to level of NT-proBNP and
      HFSS was analyzed in logistic regression models. RESULTS: Median NT-proBNP level
      in men was 1,394 ng/l (IQR 516-3,406 ng/l) and 1,168 ng/l (IQR 444-2,830 ng/l) in
      women (p = n.s.). Median HFSS value was 8.4 (IQR 7.7-9.1) and 8.5 (8.0-9.1) in
      men and women, respectively. NT-proBNP levels and HFSS score correlated well with
      survival rates in both genders (p for interaction = 0.22 for NT-proBNP and 0.93
      for HFSS). The all-cause death rates were similar in men and women. CONCLUSION:
      Despite a number of gender-specific differences in CHF and the general
      predominance of men measured levels of NT-proBNP and HFSS score can be utilized
      for risk stratification with similar informative value in men and women.

PMID- 25373386
TI  - Involvement of trace elements in the pathogenesis of prion diseases.
AB  - Prion diseases are progressive neurodegenerative diseases that are associated
      with conformational changes that convert normal cellular prion protein (PrP(C))
      into an abnormal pathogenic prion protein (PrP(Sc)). It is widely recognized that
      prion diseases are forms of transmissible amyloidosis and are considered to be
      protein-misfolding diseases (conformational diseases), a category that also
      includes Alzheimer's disease. Trace elements play crucial roles in the
      conformational change affecting PrP(C), and increasing evidence suggests that
      PrP(C) is a metal-binding protein that is involved in the homeostasis of Cu, Zn,
      and Fe. In this article, we review the current understanding of links between
      trace elements and the conformational change to PrP(Sc), based on our studies
      using synthetic prion peptides, as well as other new findings. We also focus on
      PrP(Sc)-induced disruption of Ca homeostasis as a molecular mechanism for
      neurodegeneration in prion diseases. Possible roles of carnosine (beta-alanyl
      histidine) as a candidate neuroprotective substance use in prion diseases are
      also discussed. 

PMID- 25373387
TI  - A survey and a molecular dynamics study on the (central) hydrophobic region of
      prion proteins.
AB  - Prion diseases which are serious neurodegenerative diseases that affect humans
      and animals occur in various of species. Unlike many other neurodegenerative
      diseases affected by amyloid, prion diseases can be highly infectious. Prion
      diseases occur in many species. In humans, prion diseases include the fatal human
      neurodegenerative diseases such as Creutzfeldt-Jakob Disease (CJD), Fatal
      Familial Insomnia (FFI), Gerstmann-Strussler-Scheinker syndrome (GSS) and Kuru
      etc. In animals, prion diseases are related to the bovine spongiform
      encephalopathy (BSE or 'mad-cow' disease) in cattle, the chronic wasting disease
      (CWD) found in deer and elk, and scrapie seen in sheep and goats, etc. More
      seriously, the fact that transmission of the prion diseases across the species
      barrier to other species such as humans has caused a major public health concern
      worldwide. For example, the BSE in Europe, the CWD in North America, and variant
      CJDs (vCJDs) in young people of UK. Fortunately, it is discovered that the
      hydrophobic region of prion proteins (PrP) controls the formation of diseased
      prions (PrP(Sc)), which provide some clues in control of such diseases. This
      article provides a detailed survey of recent studies with respect to the PrP
      hydrophobic region of human PrP(110-136) using molecular dynamics studies. 

PMID- 25373385
TI  - Yeast prions help identify and define chaperone interaction networks.
AB  - Proteins in the cell experience various stressful conditions that can affect
      their ability to attain and maintain the structural conformations they need to
      perform effectively. Protein chaperones are an important part of a cellular
      protein quality control system that protects the integrity of the proteome in the
      face of such challenges. Chaperones from different conserved families have
      multiple members that cooperate to regulate each other's activity and produce
      machines that perform a variety of tasks. The large numbers of related chaperones
      with both functionally overlapping and distinct activities allows fine-tuning of
      the machinery for specific tasks, but presents a daunting degree of complexity.
      Yeast prions are misfolded forms of cellular proteins whose propagation depends
      on the action of protein chaperones. Studying how propagation of yeast prions is
      affected by alterations in functions of various chaperones provides an approach
      to understanding this complexity. 

PMID- 25373388
TI  - MCRS1 overexpression, which is specifically inhibited by miR-129*, promotes the
      epithelial-mesenchymal transition and metastasis in non-small cell lung cancer.
AB  - BACKGROUND: Although tumor invasion and metastasis are both classical hallmarks
      of cancer malignancy and the major causes of poor clinical outcomes among cancer
      patients, the underlying master regulators of invasion and metastasis remain
      largely unknown. In this study, we observed that an overexpression of
      microspherule protein 1 (MCRS1) promotes the invasion and metastasis of non-small
      cell lung cancer (NSCLC) cells. Furthermore, we sought to systematically
      investigate the pathophysiological functions and related mechanisms of MCRS1.
      METHODS: Retrovirus-mediated RNA interference was employed to knockdown MCRS1
      expression in NSCLC cell lines. Quantitative real-time polymerase chain reaction
      (qRT-PCR) and western blot respectively were used to measure levels of mRNA and
      protein. Further cell permeability assessment, invasion and proliferation assays
      were conducted to evaluate MCRS1 functions in vitro while nude mice experiments
      were performed to examine metastatic capability in vivo. Microarray analysis and
      microRNA (miRNA) sequencing were respectively carried out for mRNA and miRNA
      expression profiling, while chromatin immunoprecipitation (ChIP), luciferase
      reporter assay, and miRNA transfection were used to investigate the interaction
      between MCRS1 and miRNAs. RESULTS: MCRS1 knockdown induced morphological
      alterations, increased monolayer integrity, decreased cellular invasion and
      metastasis, and attenuated stemness and drug resistance among tested NSCLC cells.
      The levels of MCRS1 expression were likewise correlated with tumor metastasis
      among NSCLC patients. We identified differentially expressed genes after MCRS1
      silencing, which included cell junction molecules, such as ZO-1, Occludin, E
      cadherin, and DSG2. However, these differentially expressed genes were not
      directly recognized by a transcriptional complex containing MCRS1. Furthermore,
      we found that MCRS1 binds to the miR-155 promoter and regulates its expression,
      as well as MCRS1 promotes epithelial-mesenchymal transition (EMT), invasion, and
      metastasis through the up-regulation of miR-155. Systematic investigations
      ultimately showed that MCRS1 was directly and negatively regulated by the binding
      of miR-129* to its 3'-UTR, with miR-129* overexpression suppressing the growth
      and invasion of NSCLC cells. CONCLUSIONS: MiR-129* down-regulation induced MCRS1
      overexpression, which promotes EMT and invasion/metastasis of NSCLC cells through
      both the up-regulation of miR-155 and down-regulation of cell junction molecules.
      This miR-129*/MCRS1/miR-155 axis provides a new angle in understanding the basis
      for the invasion and metastasis of lung cancer.

PMID- 25373389
TI  - Synergetic effects of hBMSCs and hPCs in osteogenic differentiation and their
      capacity in the repair of critical-sized femoral condyle defects.
AB  - Tissue-engineered bone grafts require an osteoblastic cellular source to be
      utilized in bone transplantation therapy. Human bone marrow stem cells (hBMSCs)
      and periosteal-derived stem cells (hPCs) are the commonly used cellular sources
      for bone tissue engineering and are essential in fracture healing. In the present
      study, hBMSCs and hPCs were co-cultured from the same donors, as the cellular
      source. In monolayer cultivation, co-culturing hBMSCs and hPCs demonstrated more
      robust mineralized nodule formation and stronger alkaline phosphatase (ALP)
      positive staining than hBMSCs or hPCs. Three-dimensional (3-D) culturing on
      porous beta-tricalcium phosphate (TCP) scaffolds and co-culturing of hBMSCs and
      hPCs significantly promoted the osteogenic specific mRNA expression of
      COL1alpha1, BMP-2, osteopontin (OPN) and osteocalcin (OC). For in vivo bone
      formation and neovascularization assessment, the cellular-beta-TCP scaffolds were
      transplanted into critical-sized femoral condyle defects in rabbits. The results
      confirmed that co-culturing hBMSCs and hPCs accelerated bone regeneration and
      enhanced mature bone formation, but also facilitated central vascularization in
      scaffold pores. Based on these data, we recommend co-culturing hBMSCs and hPCs as
      a promising cellular source for bone tissue engineering applications. 

PMID- 25373390
TI  - Qualitative feedback from a text messaging intervention for depression: benefits,
      drawbacks, and cultural differences.
AB  - BACKGROUND: Mobile health interventions are often standardized and assumed to
      work the same for all users; however, we may be missing cultural differences in
      the experiences of interventions that may impact how and if an intervention is
      effective. OBJECTIVE: The objective of the study was to assess qualitative
      feedback from participants to determine if there were differences between Spanish
      speakers and English speakers. Daily text messages were sent to patients as an
      adjunct to group Cognitive Behavioral Therapy (CBT) for depression. METHODS:
      Messages inquired about mood and about specific themes (thoughts, activities,
      social interactions) of a manualized group CBT intervention. There were thirty
      nine patients who participated in the text messaging pilot study. The average age
      of the participants was 53 years (SD 10.4; range of 23-72). RESULTS: Qualitative
      feedback from Spanish speakers highlighted feelings of social support, whereas
      English speakers noted increased introspection and self-awareness of their mood
      state. CONCLUSIONS: These cultural differences should be explored further, as
      they may impact the effect of supportive mobile health interventions. TRIAL
      REGISTRATION:  TRIAL REGISTRATION: Clinicaltrials.gov NCT01083628;
      http://clinicaltrials.gov/ct2/show/study/NCT01083628 (Archived by WebCite at
      http://www.webcitation.org/6StpbdHuq).

PMID- 25373391
TI  - Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo
      controlled, double-blind clinical trial with amitriptyline as a comparator.
AB  - BACKGROUND: Less than 50% of patients experience sufficient pain relief with
      current drug therapy for neuropathic pain. Minocycline shows promising results in
      rodent models of neuropathic pain but was not studied in humans with regard to
      the treatment of neuropathic pain. METHODS: In this randomized, double-blind,
      placebo-controlled clinical trial, patients with subacute lumbar radicular pain
      received placebo, amitriptyline 25 mg, or minocycline 100 mg once a day (n = 20
      per group) for 14 days. Primary outcome measure was the pain intensity in the leg
      as measured by a numeric rating scale ranging from 0 to 10 on days 7 and 14.
      Secondary outcome measures were the reduction of neuropathic pain symptoms in the
      leg as determined with a neuropathic pain questionnaire, consumption of rescue
      medication, and adverse events on days 7 and 14. RESULTS: Sixty patients were
      randomized and included in an intention-to-treat analysis. After 14 days,
      patients in the minocycline and amitriptyline groups reported a reduction of 1.47
      (95% confidence interval, 0.16-2.83; P = 0.035) and 1.41 (95% confidence
      interval, 0.05-2.78; P = 0.043), respectively, in the numeric rating scale
      compared to the placebo group. No differences were seen in the neuropathic pain
      questionnaire values at any time point during treatment between the three groups.
      The rate of adverse events in the amitriptyline group was 10% versus none in the
      minocycline and placebo groups. No differences were noted in the consumption of
      rescue medication. CONCLUSIONS: Although both groups differed from placebo, their
      effect size was small and therefore not likely to be clinically meaningful.

PMID- 25373392
TI  - Ethanol extract of Forsythia suspensa root induces apoptosis of esophageal
      carcinoma cells via the mitochondrial apoptotic pathway.
AB  - Forsythia suspensa root is used in the treatment of fever and jaundice in
      Traditional Chinese Medicine. In the present study, the anti-tumor activity of
      the ethanolic extract of Forsythia suspensa root (FSREE) against esophageal
      carcinoma cells was investigated in vitro and in vivo and its anti-cancer
      mechanism was examined. The results revealed that FSREE, rather than Forsythia
      suspensa ethanolic extracts from the leaf (FSLEE) and fruit (FSFEE) exhibited
      marked anti-tumor activity towards human esophageal cancer cells. FSREE induced
      cancer cell apoptosis and growth arrest by downregulating B-cell lymphoma (Bcl)
      2, Bcl-extra large and myeloid cell leukemia 1, while upregulating Bcl-2
      associated X protein, Bcl-2 antagonist of cell death and phorbol-12-myristate-13
      acetate-induced protein 1. This led to the activation of poly(ADP ribose)
      polymerase, caspase-3 and caspase-9, but not caspase-8. Furthermore, the anti
      cancer activity of FSREE was associated with a decreased level of phosphorylated
      Janus kinase/signal transducer and activator of transcription 3 and extracellular
      signal-regulated kinase signaling activity. It was also observed that the levels
      of cytochrome c were elevated in the cytoplasm, accounting for the loss of
      mitochondrial membrane potential in the TE-13 cells upon treatment with FSEER. In
      addition, FSEER inhibited the growth of esophageal cancer cells in xenograft
      models and no detectable toxicity was present in the lung or liver tissues. These
      observations provided further evidence of the anti-tumor effect of FSEER and may
      be of importance to further examine the potential role of Forsythia suspensa root
      as a therapeutic agent in esophageal carcinoma therapy.

PMID- 25373394
TI  - Physician assistants in Israel.

PMID- 25373393
TI  - Hemolytic uremic syndrome with simultaneous Shiga toxin producing Escherichia
      coli and complement abnormalities.
AB  - BACKGROUND: Hemolytic uremic syndrome is a common cause of acute kidney injury in
      children. In children, hemolytic uremic syndrome is most commonly associated with
      gastrointestinal infections caused by Shiga toxin-producing Escherichia coli or
      other enteric organisms. Although less common, atypical hemolytic uremic syndrome
      is triggered by multiple factors and portends a significantly worse prognosis
      with a high rate of recurrence. CASE PRESENTATION: Here we discuss the case of a
      10 year old Caucasian male presenting with thrombocytopenia, anemia, and acute
      kidney injury. CONCLUSIONS: This case highlights the clinical challenges in
      diagnosing and managing patients with hemolytic uremic syndrome. Because of
      similarity in symptoms, differentiating Shiga toxin-producing Escherichia coli
      associated hemolytic uremic syndrome and atypical hemolytic uremic syndrome can
      be challenging. However, because of the increased morbidity and mortality of
      atypical hemolytic uremic syndrome, early detection and initiation of therapy are
      critical. Providers must have a heightened suspicion in order to initiate
      supportive care or disease directed therapy in the case of atypical hemolytic
      uremic syndrome.

PMID- 25373395
TI  - Missing the mark: why is some research on PAs just wrong?

PMID- 25373396
TI  - Gel electrophoretic separation of proteins from cultured neuroendocrine tumor
      cell lines.
AB  - Neuroendocrine tumors (NET) often develop asymptomatically and are detected at a
      late stage. Currently, there exist certain markers of NET that occur only in the
      advanced stages of the disease. Still, there is need to develop markers specific
      of the early stage of cancer development. Nevertheless, biomarkers are mostly low
      abundant proteins and require separation from complex protein mixtures, which
      remains a major challenge. The goal of the present study was to optimize one
      dimensional-polyacrylamide gel electrophoresis (1D-PAGE) for separation and
      comparison of protein composition from neuroendocrine tumor samples. 1D-PAGE was
      optimized by modification of the gel concentration and by comparison of different
      gel staining protocols. In addition, several steps prior to electrophoresis were
      carried out to purify and preliminarily reduce the complexity of the sample. The
      results of these optimization steps indicated that use of an albumin removal kit
      can considerably decrease the amount of albumin in the samples, thereby allowing
      to detect proteins of low abundance. Optimal separation of the sample was
      obtained using a 12% polyacrylamide gel. Furthermore, the use of silver staining
      allowed detection of proteins at nanogram levels, whereas for Coomassie Brilliant
      Blue staining, the detection limit was 10 times higher. Optimization of the
      sample preparation workflow and parameters of the electrophoretic separation
      allowed to reduce the complexity of the studied material and facilitated further
      identification of proteins of low abundance in the sample. This study
      demonstrated that analysis of the secreted proteome of NET cells by 1D-PAGE is a
      simple and suitable tool for the identification of potential NET protein
      biomarkers. 

PMID- 25373397
TI  - Bioresorbable scaffolds: focus on vascular response and long-term safety.
AB  - Bioresorbable vascular scaffolds (BVS) are considered the fourth revolution in
      Interventional Cardiology, thus promising to address some of the pending issues
      with current-generation drug eluting stents (DES). Notably, most of the potential
      advantages of BVS over other current devices are due to a peculiar vascular
      response, called "vascular restoration therapy". The emerging data from real
      world expanded use registries suggest that BVS use is feasible in a wide variety
      of patients (from low- to high- risk), and lesions (from simplex to complex).
      However, few safety concerns with currently available BVS have arised from
      initial experiences all over the word. Data from ongoing large-scale randomized
      controlled trials will be able to demonstrate whether BVS improve patient early
      and long-term outcomes compared to best-in-class DES. 

PMID- 25373398
TI  - Targeting transradial approach.
AB  - Radial access for percutaneous coronary interventions (PCI) emerged as a valid
      alternative to the standard femoral access with the aim of reduce the incidence
      of access-site bleeding and consequently improve clinical outcomes. Access-site
      bleeding is still one of the most common complications after PCI and is
      associated with increased short- and long-term morbidity and mortality. Benefits
      in access-site bleeding have been consistently observed in high-risk patients
      undergoing PCI and in particular in STEMI patients where the antithrombotic
      regimen is more aggressive. Moreover, other advantages with TR access have been
      reported including better cost-effectiveness, patient preference, reduced in
      hospital length-of-stay, earlier patient ambulation, increased safety in patients
      on oral anticoagulant and the potential for same-day hospital discharge. The
      benefits of transradial access in PCI led the interventional community to expand
      its use to endovascular interventions and more recently, to cardiac structural
      interventions such as transcatheter aortic valve implantation. The aim of this
      review is to try to give to the reader a wide view of the state-of-the-art of
      transradial access in PCI and its current use in endovascular and structural
      interventions. 

PMID- 25373399
TI  - The Application of an Etiological Model of Personality Disorders to Problem
      Gambling.
AB  - Problem gambling is a significant mental health problem that creates a multitude
      of intrapersonal, interpersonal, and social difficulties. Recent empirical
      evidence suggests that personality disorders, and in particular borderline
      personality disorder (BPD), are commonly co-morbid with problem gambling. Despite
      this finding there has been very little research examining overlapping factors
      between these two disorders. The aim of this review is to summarise the
      literature exploring the relationship between problem gambling and personality
      disorders. The co-morbidity of personality disorders, particularly BPD, is
      reviewed and the characteristics of problem gamblers with co-morbid personality
      disorders are explored. An etiological model from the more advanced BPD
      literature-the biosocial developmental model of BPD-is used to review the
      similarities between problem gambling and BPD across four domains: early parent
      child interactions, emotion regulation, co-morbid psychopathology and negative
      outcomes. It was concluded that personality disorders, in particular BPD are
      commonly co-morbid among problem gamblers and the presence of a personality
      disorder complicates the clinical picture. Furthermore BPD and problem gambling
      share similarities across the biosocial developmental model of BPD. Therefore
      clinicians working with problem gamblers should incorporate routine screening for
      personality disorders and pay careful attention to the therapeutic alliance,
      client motivations and therapeutic boundaries. Furthermore adjustments to therapy
      structure, goals and outcomes may be required. Directions for future research
      include further research into the applicability of the biosocial developmental
      model of BPD to problem gambling. 

PMID- 25373400
TI  - Reconstruction of lactate utilization system in Pseudomonas putida KT2440: a
      novel biocatalyst for l-2-hydroxy-carboxylate production.
AB  - As an important method for building blocks synthesis, whole cell biocatalysis is
      hindered by some shortcomings such as unpredictability of reactions, utilization
      of opportunistic pathogen, and side reactions. Due to its biological and
      extensively studied genetic background, Pseudomonas putida KT2440 is viewed as a
      promising host for construction of efficient biocatalysts. After analysis and
      reconstruction of the lactate utilization system in the P. putida strain, a novel
      biocatalyst that only exhibited NAD-independent D-lactate dehydrogenase activity
      was prepared and used in L-2-hydroxy-carboxylates production. Since the side
      reaction catalyzed by the NAD-independent L-lactate dehydrogenase was eliminated
      in whole cells of recombinant P. putida KT2440, two important L-2-hydroxy
      carboxylates (L-lactate and L-2-hydroxybutyrate) were produced in high yield and
      high optical purity by kinetic resolution of racemic 2-hydroxy carboxylic acids.
      The results highlight the promise in biocatalysis by the biotechnologically
      important organism P. putida KT2440 through genomic analysis and recombination.

PMID- 25373404
TI  - Organization of Hospital Nursing and 30-Day Readmissions in Medicare Patients
      Undergoing Surgery.
AB  - BACKGROUND: Growing scrutiny of readmissions has placed hospitals at the center
      of readmission prevention. Little is known, however, about hospital nursing-a
      critical organizational component of hospital service system-in relation to
      readmissions. OBJECTIVES: To determine the relationships between hospital nursing
      factors-nurse work environment, nurse staffing, and nurse education-and 30-day
      readmissions among Medicare patients undergoing general, orthopedic, and vascular
      surgery. METHOD AND DESIGN: We linked Medicare patient discharge data, multistate
      nurse survey data, and American Hospital Association Annual Survey data. Our
      sample included 220,914 Medicare surgical patients and 25,082 nurses from 528
      hospitals in 4 states (California, Florida, New Jersey, and Pennsylvania). Risk
      adjusted robust logistic regressions were used for analyses. RESULTS: The average
      30-day readmission rate was 10% in our sample (general surgery: 11%; orthopedic
      surgery: 8%; vascular surgery: 12%). Readmission rates varied widely across
      surgical procedures and could be as high as 26% (upper limb and toe amputation
      for circulatory system disorders). Each additional patient per nurse increased
      the odds of readmission by 3% (OR=1.03; 95% CI, 1.00-1.05). Patients cared in
      hospitals with better nurse work environments had lower odds of readmission
      (OR=0.97; 95% CI, 0.95-0.99). Administrative support to nursing practice
      (OR=0.96; 95% CI, 0.94-0.99) and nurse-physician relations (OR=0.97; 95% CI, 0.95
      0.99) were 2 main attributes of the work environment that were associated with
      readmissions. CONCLUSIONS: Better nurse staffing and work environment were
      significantly associated with 30-day readmission, and can be considered as system
      level interventions to reduce readmissions and associated financial penalties.

PMID- 25373403
TI  - Eliminating Health Care Disparities With Mandatory Clinical Decision Support: The
      Venous Thromboembolism (VTE) Example.
AB  - BACKGROUND: All hospitalized patients should be assessed for venous
      thromboembolism (VTE) risk factors and prescribed appropriate prophylaxis. To
      improve best-practice VTE prophylaxis prescription for all hospitalized patients,
      we implemented a mandatory computerized clinical decision support (CCDS) tool.
      The tool requires completion of checklists to evaluate VTE risk factors and
      contraindications to pharmacological prophylaxis, and then recommends the risk
      appropriate VTE prophylaxis regimen. OBJECTIVES: The objective of the study was
      to examine the effect of a quality improvement intervention on race-based and sex
      based health care disparities across 2 distinct clinical services. RESEARCH
      DESIGN: This was a retrospective cohort study of a quality improvement
      intervention. SUBJECTS: The study included 1942 hospitalized medical patients and
      1599 hospitalized adult trauma patients. MEASURES: In this study, the proportion
      of patients prescribed risk-appropriate, best-practice VTE prophylaxis was
      evaluated. RESULTS: Racial disparities existed in prescription of best-practice
      VTE prophylaxis in the preimplementation period between black and white patients
      on both the trauma (70.1% vs. 56.6%, P=0.025) and medicine (69.5% vs. 61.7%,
      P=0.015) services. After implementation of the CCDS tool, compliance improved for
      all patients, and disparities in best-practice prophylaxis prescription between
      black and white patients were eliminated on both services: trauma (84.5% vs.
      85.5%, P=0.99) and medicine (91.8% vs. 88.0%, P=0.082). Similar findings were
      noted for sex disparities in the trauma cohort. CONCLUSIONS: Despite the fact
      that risk-appropriate prophylaxis should be prescribed equally to all
      hospitalized patients regardless of race and sex, practice varied widely before
      our quality improvement intervention. Our CCDS tool eliminated racial disparities
      in VTE prophylaxis prescription across 2 distinct clinical services. Health
      information technology approaches to care standardization are effective to
      eliminate health care disparities.

PMID- 25373405
TI  - Revisiting Disparities in Quality of Care Among US Adults With Diabetes in the
      Era of Individualized Care, NHANES 2007-2010.
AB  - BACKGROUND: Diabetes quality of care standards promote uniform goals and are used
      routinely for performance measurement and reimbursement. Diabetes health
      disparities have been characterized using these universal goals. However,
      guidelines emphasize individualized goals. OBJECTIVES: To assess diabetes care
      disparities using individualized goals to (1) determine their racial/ethnic
      distribution and (2) compare disparities using individualized versus uniform
      goals. RESEARCH DESIGN, SUBJECTS, AND MEASURES: A nationally representative
      sample of non-Hispanic white, non-Hispanic black, and Hispanic adults with self
      reported diabetes aged 20 years or more in the National Health and Nutrition
      Examination Survey, 2007-2010. Individualized glycemic goals (A1C<6.5%, <7.0%, or
      <8.0%) assigned based on age, duration, complications, and comorbidity, and
      cholesterol goals [low-density lipoprotein cholesterol (LDL) <70 or <100 mg/dL]
      assigned based on cardiovascular history. RESULTS: More Hispanics were
      recommended an individualized A1C<7.0% compared with whites (54% vs. 42%,
      P=0.008). Fewer blacks and Hispanics were recommended an individualized LDL<70
      mg/dL than whites (21% and 19% vs. 28%, P=0.02 and 0.001). Fewer Hispanics had
      adequate individualized A1C control (56% vs. 68%, P<0.001), and fewer blacks and
      Hispanics had adequate individualized LDL control (31% and 36% vs. 51%, P<=0.001
      and P=0.004). A uniform A1C<7% goal did not reveal disparities in glycemic
      control; individualized A1C and LDL, blood pressure <140/90 mm Hg, and nonsmoking
      was achieved by few adults (18%), and fewer blacks and Hispanics than whites (6%
      and 11% vs. 22%, P<0.001 and P=0.005). CONCLUSIONS: Individualized goals for
      diabetes care may unearth greater racial/ethnic disparities in clinical
      performance compared with uniform goals. Diabetes performance measures should
      include individualized goals to prevent worsening disparities in diabetes
      outcomes.

PMID- 25373406
TI  - Has Hospice Use Changed? 2000-2010 Utilization Patterns.
AB  - BACKGROUND: Hospice use has increased substantially during the past decade by an
      increasingly diverse patient population; however, little is known about patterns
      of hospice use and how these patterns have changed during the past decade.
      OBJECTIVE: To characterize Medicare hospice users in 2000 and 2010 and estimate
      the prevalence of (1) very short (<=1 wk) hospice enrollment; (2) very long (>6
      mo) hospice enrollment; and (3) hospice disenrollment and how these utilization
      patterns have varied over time and by patient and hospice characteristics.
      RESEARCH DESIGN: Cross-sectional analysis of Medicare hospice claims data from
      2000 and 2010. SUBJECTS: All US Medicare Hospice Benefit enrollees in 2000
      (N=529,573) and 2010 (N=1,150,194). RESULTS: As of 2010, more than half (53.4%)
      of all Medicare decedents who used hospice had either very short (<=1 wk, 32.4%)
      or very long (>6 mo, 13.9%) hospice enrollment or disenrolled from hospice before
      death (10.6%). This represents an increase of 4.9 percentage points from 2000. In
      multivariable analysis, patients with noncancer diagnoses, the fastest growing
      group of hospice users, were approximately twice as likely as those with cancer
      to have very short or long enrollment periods and to disenroll from hospice.
      CONCLUSION: The substantial proportion of hospice users with very short or long
      enrollment, or enrollments that end before death, underscores the potential for
      interventions to improve the timing and appropriateness of hospice referral so
      that the full benefits of hospice are received by patients and families.

PMID- 25373407
TI  - Developing and Evaluating Composite Measures of Cancer Care Quality.
AB  - BACKGROUND: Composite measures are useful for distilling quality data into
      summary scores; yet, there has been limited use of composite measures for cancer
      care. OBJECTIVE: Compare multiple approaches for generating cancer care composite
      measures and evaluate how well composite measures summarize dimensions of cancer
      care and predict survival. STUDY DESIGN: We computed hospital-level rates for 13
      colorectal, lung, and prostate cancer process measures in 59 Veterans Affairs
      hospitals. We computed 4 empirical-factor (based on an exploratory factor
      analysis), 3 cancer-specific (colorectal, lung, prostate care), and 3 care
      modality-specific (diagnosis/evaluation, surgical, nonsurgical treatments)
      composite measures. We assessed correlations among all composite measures and
      estimated all-cause survival for colon, rectal, non-small cell lung, and small
      cell lung cancers as a function of composite scores, adjusting for patient
      characteristics. RESULTS: Four factors emerged from the factor analysis:
      nonsurgical treatment, surgical treatment, colorectal early diagnosis, and
      prostate treatment. We observed strong correlations (r) among composite measures
      comprised of similar process measures (r=0.58-1.00, P<0.0001), but not among
      composite measures reflecting different care dimensions. Composite measures were
      rarely associated with survival. CONCLUSIONS: The empirical-factor domains
      grouped measures variously by cancer type and care modality. The evidence did not
      support any single approach for generating cancer care composite measures. Weak
      associations across different care domains suggest that low-quality and high
      quality cancer care delivery may coexist within Veterans Affairs hospitals.

PMID- 25373408
TI  - Serbian version of the Women's Health Questionnaire: psychometric properties.
AB  - OBJECTIVE: The aim of this study was to translate the Women's Health
      Questionnaire (WHQ) into the Serbian language and assess its validity and
      reliability in a population of Serbian menopausal women. METHODS: The study
      included peri- and postmenopausal women from two Community Health Centers in
      Belgrade. Women filled out the WHQ, the Short Form-36 questionnaire (SF-36) and
      Beck's Depression Inventory (BDI). The WHQ was translated according to
      recommended methodology for cultural adaptation of questionnaires and its
      psychometric characteristics (internal consistency, inter-rater reliability,
      factor analysis, sensitivity, discriminant, construct and criterion validity)
      were tested. RESULTS: In the Serbian population, the mean values of the WHQ
      domains were mostly comparable with reference Mediterranean countries. Whole
      scale Cronbach's alpha was 0.838. Moreover, five WHQ domains had a value of
      Cronbach's alpha above the acceptable limit. There were no significant
      differences in WHQ scores between our two investigators. On exploratory factor
      analysis, we obtained ten factors (two items formed a new factor - 'Menstrual
      pathology'). Almost all SF-36 domains were significantly associated with WHQ
      domains, while the BDI was associated with domains: depressive mood, anxiety and
      sleep problems. Based on ROC analysis, WHQ is slightly more reliable for
      perimenopausal than postmenopausal Serbian women. CONCLUSION: The Serbian version
      of the WHQ showed very good reliability and validity in assessment of quality of
      life among menopausal women. The WHQ is applicable for both peri- and
      postmenopausal women.

PMID- 25373409
TI  - Developing a targeting system for bacterial membranes: measuring receptor
      phosphatidylglycerol interactions with (1)H NMR, ITC and fluorescence correlation
      spectroscopy.
AB  - An ammonium picket porphyrin that targets bacterial membranes has been prepared
      and shown to bind to phosphatidylglycerol (PG), a bacterial lipid, when the lipid
      was in solution, contained within synthetic membrane vesicles, or when in Gram
      negative and Gram-positive bacterial membranes. The multifunctional receptor was
      designed to interact with both the phosphate anion portion and neutral glycerol
      portion of the lipid headgroup. The receptor's affinity and selectivity for
      binding to surfactant vesicles or lipid vesicles that contain PG within their
      membranes was directly measured using fluorescence correlation spectroscopy
      (FCS). FCS demonstrated that the picket porphyrin's binding pocket was
      complementary for the lipid headgroup, since simple Coulombic interactions alone
      did not induce binding. (1)H NMR and isothermal titration calorimetry (ITC) were
      used to determine the receptor's binding stoichiometry, receptor-lipid complex
      structure, binding constant, and associated thermodynamic properties of
      complexation in solution. The lipid-receptor binding motif in solution was shown
      to mirror the binding motif of membrane-bound PG and receptor. Cell lysis assays
      with E. coli (Gram-negative) and Bacillus thuringiensis (Gram-positive) probed
      with UV/Visible spectrophotometry indicated that the receptor was able to
      penetrate either bacterial cell wall and to bind to the bacterial inner membrane.

PMID- 25373410
TI  - Prognostic impact of alternative splicing-derived hMENA isoforms in resected,
      node-negative, non-small-cell lung cancer.
AB  - Risk assessment and treatment choice remain a challenge in early non-small-cell
      lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic,
      prognostic and therapeutic tools. Here, we investigated the prognostic value of
      the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and
      hMENADeltav6, in early NSCLC. The epithelial hMENA11a isoform was expressed in
      NSCLC lines expressing E-CADHERIN and was alternatively expressed with
      hMENADeltav6. Enforced expression of hMENADeltav6 or hMENA11a increased or
      decreased the invasive ability of A549 cells, respectively. hMENA isoform
      expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low
      hMENA11a were the only independent predictors of shorter disease-free and cancer
      specific survival, and low hMENA11a was an independent predictor of shorter
      overall survival, at multivariate analysis. Patients with low pan-hMENA/high
      hMENA11a expression fared significantly better (P<=0.0015) than any other
      subgroup. Such hybrid variable was incorporated with T-size and number of
      resected lymph nodes into a 3-class-risk stratification model, which strikingly
      discriminated between different risks of relapse, cancer-related death, and
      death. The model was externally validated in an independent dataset of 133
      patients. Relative expression of hMENA splice isoforms is a powerful prognostic
      factor in early NSCLC, complementing clinical parameters to accurately predict
      individual patient risk. 

PMID- 25373411
TI  - Important issues concerning use of term 'copers' in chronic ankle instability
      research.

PMID- 25373412
TI  - Author's Reply to Liu et al.: "important issues concerning use of the term
      'copers' in chronic ankle instability research".

PMID- 25373413
TI  - Occupational heat stress and associated productivity loss estimation using the
      PHS model (ISO 7933): a case study from workplaces in Chennai, India.
AB  - BACKGROUND: Heat stress is a major occupational problem in India that can cause
      adverse health effects and reduce work productivity. This paper explores this
      problem and its impacts in selected workplaces, including industrial, service,
      and agricultural sectors in Chennai, India. DESIGN: Quantitative measurements of
      heat stress, workload estimations, and clothing testing, and qualitative
      information on health impacts, productivity loss, etc., were collected. Heat
      strain and associated impacts on labour productivity between the seasons were
      assessed using the International Standard ISO 7933:2004, which applies the
      Predicted Heat Strain (PHS) model. RESULTS AND CONCLUSIONS: All workplaces
      surveyed had very high heat exposure in the hot season (Wet Bulb Globe
      Temperature =29.7), often reaching the international standard safe work values
      (ISO 7243:1989). Most workers had moderate to high workloads (170-220 W/m2), with
      some exposed to direct sun. Clothing was found to be problematic, with high
      insulation values in relation to the heat exposure. Females were found to be more
      vulnerable because of the extra insulation added from wearing a protective shirt
      on top of traditional clothing (0.96 clo) while working. When analysing heat
      strain--in terms of core temperature and dehydration--and associated productivity
      loss in the PHS model, the parameters showed significant impacts that affected
      productivity in all workplaces, apart from the laundry facility, especially
      during the hot season. For example, in the canteen, the core temperature limit of
      38 degrees C predicted by the model was reached in only 64 min for women. With
      the expected increases in temperature due to climate change, additional
      preventive actions have to be implemented to prevent further productivity losses
      and adverse health impacts. Overall, this study presented insight into using a
      thermo-physiological model to estimate productivity loss due to heat exposure in
      workplaces. This is the first time the PHS model has been used for this purpose.
      An exploratory approach was taken for further development of the model.

PMID- 25373414
TI  - Disease burden due to biomass cooking-fuel-related household air pollution among
      women in India.
AB  - BACKGROUND: Household air pollution (HAP) due to biomass cooking fuel use is an
      important risk factor for a range of diseases, especially among adult women who
      are primary cooks, in India. About 80% of rural households in India use biomass
      fuel for cooking. The aim of this study is to estimate the attributable cases
      (AC) for four major diseases/conditions associated with biomass cooking fuel use
      among adult Indian women. METHODS: We used the population attributable fraction
      (PAF) method to calculate the AC of chronic bronchitis, tuberculosis (TB),
      cataract, and stillbirths due to exposure to biomass cooking fuel. A number of
      data sources were accessed to obtain population totals and disease prevalence
      rates. A meta-analysis was conducted to obtain adjusted pooled odds ratios (ORs)
      for strength of association. Using this, PAF and AC were calculated using a
      standard formula. Results were presented as number of AC and 95% confidence
      intervals (CI). RESULTS: The fixed effects pooled OR obtained from the meta
      analysis were 2.37 (95% CI: 1.59, 3.54) for chronic bronchitis, 2.33 (1.65, 3.28)
      for TB, 2.16 (1.42, 3.26) for cataract, and 1.26 (1.12, 1.43) for stillbirths.
      PAF varied across conditions being maximum (53%) for chronic bronchitis in rural
      areas and least (1%) for cataract in older age and urban areas. About 2.4 (95%
      CI: 1.4, 3.1) of 5.6 m cases of chronic bronchitis, 0.3 (0.2, 0.4) of 0.76 m
      cases of TB, 5.0 (2.8, 6.7) of 51.4 m cases of cataract among adult Indian women
      and 0.02 (0.01, 0.03) of 0.15 m stillbirths across India are attributable to HAP
      due to biomass cooking fuel. These estimates should be cautiously interpreted in
      the light of limitations discussed which relate to exposure assessment, exposure
      characterization, and age-specific prevalence of disease. CONCLUSIONS: HAP due to
      biomass fuel has diverse and major impacts on women's health in India. Although
      challenging, incorporating the agenda of universal clean fuel access or cleaner
      technology within the broader framework of rural development will go a long way
      in reducing disease burden.

PMID- 25373415
TI  - Vulnerability of Bangladeshi street-children to HIV/AIDS: a qualitative study.
AB  - BACKGROUND: Children living on the streets are an underprivileged population of
      Bangladesh and are likely to be more vulnerable to STIs/HIV for their day-to-day
      risky behaviours and lifestyles. This study assessed the vulnerability of
      Bangladeshi street-children to HIV/AIDS using qualitative participatory methods.
      METHODS: This ethnographic participatory, qualitative study was conducted during
      February 2010- December 2011 among children aged 5-12 years, who live and/or work
      on the streets in Dhaka, the capital city of Bangladesh. Data were collected in
      three phases: (a) social mapping (n = 493), (b) participatory group discussions
      (n = 119), and (c) individual interviews (n = 36). RESULTS: Results showed that
      street-children were engaged in behaviour that entails risk of exposure to
      HIV/AIDS. They possessed poor knowledge of the transmission of disease and of the
      benefits of using condoms; most of them reported never using a condom. The
      experience of selling sex for money and a variety of sexual activities, like
      anal, vaginal and oral sex, were commonly reported. The children also reported
      that they were regular users of one or more types of drugs, including those taken
      by injection. CONCLUSIONS: The deplorable living conditions of street children,
      with no obvious rights or way out, make them highly vulnerable to HIV/AIDS.
      Urgent attention of the policy- makers to implement services addressing issues
      relating to social conditions, sexual health, and drug-use is warranted to
      prevent the possible epidemic of HIV/AIDS among this group of population.

PMID- 25373416
TI  - Attribution of the United States "warming hole": aerosol indirect effect and
      precipitable water vapor.
AB  - Aerosols can influence the climate indirectly by acting as cloud condensation
      nuclei and/or ice nuclei, thereby modifying cloud optical properties. In contrast
      to the widespread global warming, the central and south central United States
      display a noteworthy overall cooling trend during the 20(th) century, with an
      especially striking cooling trend in summertime daily maximum temperature (Tmax)
      (termed the U.S. "warming hole"). Here we used observations of temperature,
      shortwave cloud forcing (SWCF), longwave cloud forcing (LWCF), aerosol optical
      depth and precipitable water vapor as well as global coupled climate models to
      explore the attribution of the "warming hole". We find that the observed cooling
      trend in summer Tmax can be attributed mainly to SWCF due to aerosols with offset
      from the greenhouse effect of precipitable water vapor. A global coupled climate
      model reveals that the observed "warming hole" can be produced only when the
      aerosol fields are simulated with a reasonable degree of accuracy as this is
      necessary for accurate simulation of SWCF over the region. These results provide
      compelling evidence of the role of the aerosol indirect effect in cooling
      regional climate on the Earth. Our results reaffirm that LWCF can warm both
      winter Tmax and Tmin. 

PMID- 25373417
TI  - Rationally designed multifunctional plasmonic nanostructures for surface-enhanced
      Raman spectroscopy: a review.
AB  - Rationally designed multifunctional plasmonic nanostructures efficiently
      integrate two or more functionalities into a single entity, for example, with
      both plasmonic and catalytic activity. This review article is focused on their
      synthesis and use in surface-enhanced Raman scattering (SERS) as a molecular
      spectroscopic technique with high sensitivity, fingerprint specificity, and
      surface selectivity. After a short tutorial on the fundamentals of Raman
      scattering and SERS in particular, applications ranging from chemistry
      (heterogeneous catalysis) to biology and medicine (diagnostics/imaging, therapy)
      are summarized. 

PMID- 25373418
TI  - An agent-based model of the population dynamics of Anopheles gambiae.
AB  - BACKGROUND: Agent-based models (ABMs) have been used to model the behaviour of
      individual mosquitoes and other aspects of malaria. In this paper, a conceptual
      entomological model of the population dynamics of Anopheles gambiae and the agent
      based implementations derived from it are described. Hypothetical vector control
      interventions (HVCIs) are implemented to target specific activities in the
      mosquito life cycle, and their impacts are evaluated. METHODS: The core model is
      described in terms of the complete An. gambiae mosquito life cycle. Primary
      features include the development and mortality rates in different aquatic and
      adult stages, the aquatic habitats and oviposition. The density- and age
      dependent larval and adult mortality rates (vector senescence) allow the model to
      capture the age-dependent aspects of the mosquito biology. Details of
      hypothetical interventions are also described. RESULTS: Results show that with
      varying coverage and temperature ranges, the hypothetical interventions targeting
      the gonotrophic cycle stages produce higher impacts than the rest in reducing the
      potentially infectious female (PIF) mosquito populations, due to their multi-hour
      mortality impacts and their applicability at multiple gonotrophic cycles. Thus,
      these stages may be the most effective points of target for newly developed and
      novel interventions. A combined HVCI with low coverage can produce additive
      synergistic impacts and can be more effective than isolated HVCIs with
      comparatively higher coverages. It is emphasized that although the model
      described in this paper is designed specifically around the mosquito An. gambiae,
      it could effectively apply to many other major malaria vectors in the world
      (including the three most efficient nominal anopheline species An. gambiae,
      Anopheles coluzzii and Anopheles arabiensis) by incorporating a variety of
      factors (seasonality cycles, rainfall, humidity, etc.). Thus, the model can
      essentially be treated as a generic Anopheles model, offering an excellent
      framework for such extensions. The utility of the core model has also been
      demonstrated by several other applications, each of which investigates well
      defined biological research questions across a variety of dimensions (including
      spatial models, insecticide resistance, and sterile insect techniques).

PMID- 25373419
TI  - Immunity to polio, measles and rubella in women of child-bearing age and
      estimated congenital rubella syndrome incidence, Cambodia, 2012.
AB  - Significant gaps in immunity to polio, measles, and rubella may exist in adults
      in Cambodia and threaten vaccine-preventable disease (VPD) elimination and
      control goals, despite high childhood vaccination coverage. We conducted a
      nationwide serological survey during November-December 2012 of 2154 women aged 15
      39 years to assess immunity to polio, measles, and rubella and to estimate
      congenital rubella syndrome (CRS) incidence. Measles and rubella antibodies were
      detected by IgG ELISA and polio antibodies by microneutralization testing. Age
      structured catalytic models were fitted to rubella serological data to predict
      CRS cases. Overall, 29.8% of women lacked immunity to at least one poliovirus
      (PV); seroprevalence to PV1, PV2 and PV3 was 85.9%, 93.4% and 83.3%,
      respectively. Rubella and measles antibody seroprevalence was 73.3% and 95.9%,
      respectively. In the 15-19 years age group, 48.2% [95% confidence interval (CI)
      42.4-54.1] were susceptible to either PV1 or PV3, and 40.3% (95% CI 33.0-47.5) to
      rubella virus. Based on rubella antibody seroprevalence, we estimate that >600
      infants are born with CRS in Cambodia annually. Significant numbers of Cambodian
      women are still susceptible to polio and rubella, especially those aged 15-19
      years, emphasizing the need to include adults in VPD surveillance and a potential
      role for vaccination strategies targeted at adults.

PMID- 25373420
TI  - Exploration of molecular genetic etiology for Korean cochlear implantees with
      severe to profound hearing loss and its implication.
AB  - BACKGROUND: Severe to profound sensorineural hearing loss (SNHL) requires
      cochlear implantation (CI) for auditory rehabilitation. Etiologic diagnoses can
      contribute to candidacy selection and decision-making regarding the timing of
      successful CI. However, few studies have been performed to address the etiologic
      spectrum of severe SNHL in the population where there is no consanguineous
      marriage and the majority of SNHL cases are sporadic in small sized families. The
      authors sought to comprehensively understand the etiologies of Korean cochlear
      implantees by incorporating the targeted resequencing of 204 candidate deafness
      genes (TRS-204) and a phenotype-driven candidate gene approach. METHODS: Ninety
      three that consented to molecular genetic testing and underwent at least one
      molecular genetic test were included. Patients with a characteristic Phenotypic
      marker were subject to Sanger sequencing to detect variants in corresponding
      candidate genes. The rest of patients without any prominent phenotype were tested
      on GJB2. Next, TRS-204 was applied in GJB2-negative cases without any phenotypic
      marker. In addition, the sibling recurrence-risk of SNHL among families with non
      diagnostic genotypes after TRS-204 was performed to gain insight of etiologies in
      non-diagnostic cases. RESULTS: Overall, we could find causative variants in 51
      (54.8%) of the 93 cochlear implantees. Thirty (32.3%) probands could be diagnosed
      by direct Sanger sequencing of candidate genes selected by their phenotypes. GJB2
      sequencing added 10 subjects to the group with a diagnostic genotype. TRS-204
      could detect a causative variant from additional 11 cases (11.8%). We could not
      detect any pathogenic deletion or duplication on 204 target genes. The sibling
      recurrence-risk of SNHL among 42 genetically undiagnosed families with 0.03
      (1/38) was significantly lower than among genetically diagnosed recessive
      families with 0.19 (7/37). CONCLUSION: Despite that the majority of severe or
      more degree of SNHL occurs sporadically in Koreans, at least 54.8% of such cases
      that were willing to join the genetic study in the Korean population are
      monogenic Mendelian disorders with convincing causative variants. This study also
      indicates that a substantial portion of unsolved cases after applying our current
      protocol are predicted to have non-genetic or complex etiology rather than a
      Mendelian genetic disorder involving new genes beyond the 204 target genes.

PMID- 25373422
TI  - Multiprotocol-induced plasticity in artificial synapses.
AB  - We suggest a 'universal' electrical circuit for the realization of an artificial
      synapse that exhibits long-term plasticity induced by different protocols. The
      long-term plasticity of the artificial synapse is basically attributed to the
      nonvolatile resistance change of the bipolar resistive switch in the circuit. The
      synaptic behaviour realized by the circuit is termed 'universal' inasmuch as (i)
      the shape of the action potential is not required to vary so as to implement
      different plasticity-induction behaviours, activity-dependent plasticity (ADP)
      and spike-timing-dependent plasticity (STDP), (ii) the behaviours satisfy several
      essential features of a biological chemical synapse including firing-rate and
      spike-timing encoding and unidirectional synaptic transmission, and (iii) both
      excitatory and inhibitory synapses can be realized using the same circuit but
      different diode polarity in the circuit. The feasibility of the suggested circuit
      as an artificial synapse is demonstrated by conducting circuit calculations and
      the calculation results are introduced in comparison with biological chemical
      synapses. 

PMID- 25373423
TI  - Synthesis, structure and photophysical properties of a highly luminescent
      terpyridine-diphenylacetylene hybrid fluorophore and its metal complexes.
AB  - A new fluorescent terpyridyl-diphenylacetylene hybrid fluorophore 4'-[4-{(4
      methoxyphenyl)ethynyl}phenyl]-2,2':6',2''-terpyridine, L, was synthesized via
      Sonogashira cross-coupling of 4'-(4-bromophenyl)-2,2':6',2''-terpyridine and 4
      ethynylanisole in the presence of Pd(PPh3)4/CuI as a catalyst. The solid state
      structure of L shows a trans arrangement of pyridine nitrogen atoms along the
      interannular bond in the terpyridine domain. Five transition metal complexes of
      L, {[FeL2](CF3SO3)2 (1), [ZnL2](ClO4)2 (2), [CdL2](ClO4)2 (3), [RuL2](PF6)2 (4),
      and PtMe3IL (5)}, have also been synthesized and characterized by spectroscopic
      methods and single crystal X-ray analysis. The X-ray crystal structures of
      complexes 1-3 show a distorted octahedral MN6 arrangement with tridentate
      coordination of the two terpyridine ligands, whereas in complex 5 the ligand L
      binds in a bidentate fashion. The ligand L displays bright blue emission in the
      solid state and in both non-polar and polar organic media. The fluorescence
      quantum yield of L is exceptionally high for a monoterpyridine ligand of its
      kind, which can be rationalized with density functional theory calculations. The
      electronic structure of L shows that the fluorescence involves intramolecular
      charge transfer from the diphenylacetylene moiety to the terpyridine group, and
      it is not affected by the usual non-radiative relaxation processes such as
      pyridine rotation. The Fe(II), Ru(II) and Pt(IV) complexes of L were found to be
      non-emissive, whereas both Zn(II) and Cd(II) complexes displayed significant
      green emission attributed to intra-ligand charge transfer states. These results
      were supported by the observed red-shift of the emission maxima of complexes 2
      and 3 with increasing the solvent polarity.

PMID- 25373421
TI  - De-novo assembly of mango fruit peel transcriptome reveals mechanisms of mango
      response to hot water treatment.
AB  - BACKGROUND: The mango belongs to the genus Mangifera, consisting of numerous
      tropical fruiting trees in the flowering plant family, Anacardiaceae. Postharvest
      treatment by hot water brushing (HWB) for 15-20 s was introduced commercially to
      improve fruit quality and reduce postharvest disease. This treatment enabled
      successful storage for 3-4 weeks at 12 degrees C, with improved color and reduced
      disease development, but it enhanced lenticel discoloration on the fruit peel. We
      investigated global gene expression induced in fruit peel by HWB treatment, and
      identified key genes involved in mechanisms potentially associated with fruit
      resistance to pathogens, peel color improvement, and development of lenticel
      discoloration; this might explain the fruit's phenotypic responses. RESULTS: The
      mango transcriptome assembly was created and characterized by application of RNA
      seq to fruit-peel samples. RNA-seq-based gene-expression profiling identified
      three main groups of genes associated with HWB treatment: 1) genes involved with
      biotic and abiotic stress responses and pathogen-defense mechanisms, which were
      highly expressed; 2) genes associated with chlorophyll degradation and
      photosynthesis, which showed transient and low expression; and 3) genes involved
      with sugar and flavonoid metabolism, which were highly expressed. CONCLUSIONS: We
      describe a new transcriptome of mango fruit peel of cultivar Shelly. The
      existence of three main groups of genes that were differentially expressed
      following HWB treatment suggests a molecular basis for the biochemical and
      physiological consequences of the postharvest HWB treatment, including resistance
      to pathogens, improved color development, and occurrence of lenticel
      discoloration.

PMID- 25373425
TI  - Durability of antiretroviral therapy and predictors of virologic failure among
      perinatally HIV-infected children in Tanzania: a four-year follow-up.
AB  - BACKGROUND: In Tanzania, HIV-1 RNA testing is rarely available and not standard
      of care. Determining virologic failure is challenging and resistance mutations
      accumulate, thereby compromising second-line therapy. We evaluated durability of
      antiretroviral therapy (ART) and predictors of virologic failure among a
      pediatric cohort at four-year follow-up. METHODS: This was a prospective cross
      sectional study with retrospective chart review evaluating a perinatally HIV
      infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13.
      Demographic, clinical, and laboratory data were extracted from charts, resistance
      mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained.
      RESULTS: 161 (78%) participants of the original cohort consented to repeat HIV
      RNA. The average age was 12.2 years (55% adolescents >=12 years). Average time on
      ART was 6.4 years with 41% receiving second-line (protease inhibitor based)
      therapy. Among those originally suppressed on a first-line (non-nucleoside
      reverse transcriptase based regimen) 76% remained suppressed. Of those originally
      failing first-line, 88% were switched to second-line and 72% have suppressed
      virus. Increased level of viremia and duration of ART trended with an increased
      number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds
      of virologic failure (p = 0.18), as did adolescent age (p < 0.01). CONCLUSIONS:
      After viral load testing in 2008-09 many participants switched to second-line
      therapy. The majority achieved virologic suppression despite multiple resistance
      mutations. Though virologic testing would likely hasten the switch to second-line
      among those failing, methods to improve adherence is critical to maximize
      durability of ART and improve virologic outcomes among youth in resource-limited
      settings.

PMID- 25373426
TI  - Physicochemical characteristics and gastrointestinal absorption behaviors of S
      propargyl-cysteine, a potential new drug candidate for cardiovascular protection
      and antitumor treatment.
AB  - 1. As a potential new drug candidate for cardiovascular protection and antitumor
      treatment, the physicochemical properties, gastrointestinal (GI) absorption
      behaviors and mechanisms of S-propargyl-cysteine (SPRC) were investigated in this
      study. 2. SPRC exhibited favorable solubility in aqueous media. The log P and log
      D values were low (<=1.93 +/- 0.08). The pKa in the acidic and basic regions was
      2.08 +/- 0.02 and 8.72 +/- 0.03, respectively. The isoelectric point was 5.40 +/-
      0.02. SPRC was stable in the rat GI fluids, and showed no obvious adsorption and
      metabolism in the rat GI tract. 3. SPRC displayed poor gastric absorption and
      favorable intestinal absorption in the rat in situ GI perfusion model. Absorption
      rate constants (ka), hourly absorption percentage (P) and apparent permeability
      coefficient (Papp) of SPRC in the small intestine were >=0.77 +/- 0.06 h(-1),
      59.25 +/- 4.02% and (7.99 +/- 0.88) * 10(-5 )cm/s, respectively. Absorption of
      SPRC exhibited a certain dependence on physiological pH and absorption region.
      Absorption of SPRC was not inhibited by l-methionine and 2-aminobicyclo-(2,2,1)
      heptane-2-carboxylic acid. 4. SPRC showed favorable oral absorption. It can be
      categorized as a BCS class I drug. The membrane pore transport appeared to be one
      of the predominant absorption modes for SPRC. 

PMID- 25373427
TI  - Endorsement for improving the quality of reports on randomized controlled trials
      of traditional medicine journals in Korea: a systematic review.
AB  - The aim of this study was to assess the endorsement of reporting guidelines in
      Korean traditional medicine (TM) journals by reviewing their instructions to
      authors. We examined the instructions to authors in all of the TM journals
      published in Korea to assess the appropriate use of reporting guidelines for
      research studies. The randomized controlled trials (RCTs) published after 2010 in
      journals that endorsed reporting guidelines were obtained. The reporting quality
      was assessed using the following guidelines: the 38-item Consolidated Standards
      of Reporting Trials (CONSORT) statement for non-pharmacological trials (NPT); the
      17-item Standards for Reporting Interventions in Clinical Trials of Acupuncture
      (STRICTA) statement, instead of the 5-item CONSORT for acupuncture trials; and
      the 22-item CONSORT extensions for herbal medicine trials. The overall item score
      was calculated and expressed as a proportion.One journal that endorsed reporting
      guidelines was identified. Twenty-nine RCTs published in this journal after 2010
      met the selection criteria. General editorial policies such as those of the
      International Committee of Medical Journal Editors (ICMJE) were endorsed by 15
      journals. In each of the CONSORT-NPT articles, 21.6 to 56.8% of the items were
      reported, with an average of 11.3 items (29.7%) being reported. In the 24 RCTs
      (24/29, 82.8%) appraised using the STRICTA items, an average of 10.6 items
      (62.5%) were addressed, with a range of 41.2 to 100%. For the herbal intervention
      reporting, 17 items (77.27%) were reported. In the RCT studies before and after
      the endorsement of CONSORT and STRICTA guidelines by each journal, all of the
      STRICTA items had significant improvement, whereas the CONSORT-NPT items improved
      without statistical significance.The endorsement of reporting guidelines is
      limited in the TM journals in Korea. Authors should adhere to the reporting
      guidelines, and editorial departments should refer authors to the various
      reporting guidelines to improve the quality of their articles. 

PMID- 25373428
TI  - The debate on animal ADME studies in drug development: an update.
AB  - The preparation and release of the International Conference on Harmonisation
      guideline on safety evaluation of human metabolites and the technical progresses
      in bioanalysis have triggered an intense debate on the value of absorption,
      distribution, metabolism and excretion radiolabelled studies in animals. Some
      authors have radically challenged the traditional approach whereas others, while
      accepting the need of significant changes, argue that these studies remain an
      irreplaceable component of the preclinical registration dossier. This paper
      reviews some of the representative positions and describes the potential
      evolution. 

PMID- 25373429
TI  - Vitamin D status and thyroid autoimmunity in Korean pregnant women.
AB  - OBJECTIVE: There is increasing interest in the role of vitamin D (vitD) during
      pregnancy. We prospectively evaluated the vitD status in Korean pregnant women
      and evaluated the levels of vitD according to thyroid-specific autoimmunity
      during pregnancy. METHODS: We included pregnant 531 women who visited for
      prenatal care and 238 age-matched, non-pregnant women as a control population.
      The levels of thyrotropin, FT4, thyroid peroxidase (TPO), thyroglobulin (Tg)
      antibody (Ab) and 25-hydroxy vitamin D [25(OH)D] were measured by
      electrochemiluminescence immunoassays. RESULTS: The mean levels of 25(OH)D at
      trimester 1, 2 and 3 were 13.6, 15.6 and 19.3 ng/mL, respectively; and the
      prevalence of vitD insufficiency was 83.6%, 75.1% and 55.9%, respectively. The
      mean 25(OH)D levels were not significantly different between Tg and TPO Ab
      positive and negative pregnant women (14.9 versus 16.1, and 14.9 versus 16.1
      ng/mL, respectively). CONCLUSIONS: vitD insufficiency was exceptionally high,
      especially in the first trimester, in Korean pregnant women. The mean 25(OH)D
      levels were not significantly different according to autoimmunity. Further
      studies on this relationship could provide important information to assess the
      vitD status in patients with thyroid autoimmunity during pregnancy.

PMID- 25373430
TI  - The role of early inhaled budesonide therapy in meconium aspiration in term
      newborns: a randomized control study.
AB  - OBJECTIVE: To study the clinical spectrum of Meconium aspiration syndrome babies
      and to find out the efficacy of early nebulized steroids (Budesonide) in the
      clinical course and outcome (morbidity and mortality) of neonates with meconium
      aspiration: randomized controlled trial. METHOD AND MATERIAL: A total of 78
      neonates were included in the study. After randomization, intervention group
      received nebulization with Budesonide (0.5 mg dissolved in 2.5-ml sterile normal
      saline within 2 h of birth and second dose was given at 12 h of birth) whereas
      controls were nebulized with normal saline. All neonates were accessed for serial
      respiratory distress score (Downe's score), requirement (dependence) of oxygen
      (in days), duration of neonatal intensive-care unit (NICU) stay, any complication
      and their final outcome. RESULTS: The mean days of oxygen requirement for the
      cases and controls were 1.79 and 3.46, respectively (p < 0.001). The mean
      respiratory rate in intervention group up to the age of 5 d was significantly
      less (p value < 0.01). There was significant difference in mean Downe's score and
      mean duration of NICU stay in intervention group. CONCLUSION: Budesonide
      nebulization in meconium aspiration results in significant early improvement in
      general condition (early improvement in respiratory distress and early
      normalization of Downe's score) of the newborn with lesser oxygen requirement,
      thus early discharge from NICU but has no impact on final outcome.

PMID- 25373431
TI  - The use of magnesium sulfate for women with severe preeclampsia or eclampsia
      diagnosed during the postpartum period.
AB  - This was a systematic review of randomized controlled trials comparing
      anticonvulsants with placebo or no anticonvulsant for prevention (a) of eclampsia
      in women with severe preeclampsia diagnosed during the postpartum period or
      diagnosed before delivery but without previous treatment and (b) prevention of
      seizures recurrence in women with eclampsia postpartum. We did not find study
      with full inclusion criteria. However, a total of two randomised controlled
      trials meet inclusion criteria as subgroup analysis; one for severe preeclampsia
      diagnosed during the postpartum period and one for eclampsia postpartum. For
      severe preeclampsia diagnosed during postpartum, there was no clear difference
      between the groups reporting eclampsia (relative risk: 0.54, 95% confidence
      interval: 0.16-1.80). For seizure recurrence, magnesium sulfate was superior to
      diazepam, but there was no significant difference compared with phenytoin. No
      conclusion can be drawn on the role of magnesium sulfate post partum as
      established in antepartum pre-eclampsia/eclampsia management because of lack of
      powered randomised controlled trials. 

PMID- 25373432
TI  - The influence of placental perfusion on birthweight in women with gestational
      diabetes.
AB  - OBJECTIVE: To evaluate the influence of both uterine and umbilical arteries
      Doppler pulsatility indexes (PI) and metabolic control on birthweight in pregnant
      women with gestational diabetes mellitus. METHODS: One hundred sixty-nine women
      with gestational diabetes were evaluated. Doppler measurements of umbilical
      artery and mean uterine arteries PI were recorded and the corresponding Z-score
      values by gestational age calculated. Maternal pregestational body mass index
      (BMI) and the levels of glycosylated hemoglobin were also recorded. The
      relationships between these studied variables and customised birthweight centiles
      according to sex and gestational age were analyzed using Spearman's correlation
      coefficient and linear regression. RESULTS: There was a significant correlation
      between birthweight centiles and Z-score values of the umbilical artery PI (r = 
      0.25, p = 0.001), but not with the Z-score values of the uterine artery PI (r = 
      0.12, p = 0.43). Third trimester maternal glycosylated hemoglobin was also
      positively correlated to birthweight (r = 0.29, p = 0.01). When using stepwise
      linear regression both maternal glycosylated hemoglobin and the Z-score of
      umbilical artery PI were included as independent variables in the predictive
      model of birthweight centile (p = 0.0002, p = 0.001 respectively, R(2)( )= 0.27).
      CONCLUSIONS: Umbilical artery PI predicts birthweight in women with gestational
      diabetes. However, metabolic control is the only important determinant of fetal
      macrosomia in these mothers.

PMID- 25373435
TI  - Vaccine hesitancy, vaccine refusal and the anti-vaccine movement: influence,
      impact and implications.
AB  - Despite being recognized as one of the most successful public health measures,
      vaccination is perceived as unsafe and unnecessary by a growing number of
      parents. Anti-vaccination movements have been implicated in lowered vaccine
      acceptance rates and in the increase in vaccine-preventable disease outbreaks and
      epidemics. In this review, we will look at determinants of parental decision
      making about vaccination and provide an overview of the history of anti
      vaccination movements and its clinical impact. 

PMID- 25373436
TI  - How does semi-automated computer-derived CT measure of breast density compare
      with subjective assessments to assess mean glandular breast density, in patients
      with breast cancer?
AB  - OBJECTIVES: (a) To compare radiologists' breast mammographic density readings
      with CT subjective measures. (b) To correlate computer-derived measurement of CT
      density with subjective assessments. (c) To evaluate density distributions in
      this cohort of patients with breast cancer. METHODS: A retrospective review of
      mammograms and CT scans in 77 patients with breast cancer obtained within 1 year
      of each other was performed. Two radiologists independently reviewed both CT and
      mammograms and classified each case into four categories as defined by the breast
      imaging-reporting and data system of the American College of Radiology. Inter
      reader agreements were obtained for both mammographic and CT density subjective
      evaluations by using the Cohen-weighted kappa statistic and Spearman correlation.
      The semi-automated computer-derived measurement of breast density was correlated
      with visual measurements. RESULTS: Inter-reader agreements were lower for
      subjective CT density grades than those for mammographic readings 0.428
      [confidence interval (CI), 0.24-0.89] vs 0.571 (CI, 0.35-0.76). There was
      moderately good correlation between subjective CT density grades and the
      mammographic density grades for both readers (0.760 for Reader 1 and 0.913 for
      Reader 2). The semi-automated CT density measurement correlated well with the
      subjective assessments, with complete agreement of the density grades in 84.9% of
      patients and only one level difference in the rest. CONCLUSIONS: Semi-automated
      CT density measurements in the evaluation of breast density correlated well with
      subjective mammographic density measurement. ADVANCES IN KNOWLEDGE: There is good
      correlation between CT and mammographic density, but further studies are needed
      on how to incorporate semi-automated CT breast density measurement in the risk
      stratification of patients.

PMID- 25373437
TI  - Predicting commuter flows in spatial networks using a radiation model based on
      temporal ranges.
AB  - Understanding network flows such as commuter traffic in large transportation
      networks is an ongoing challenge due to the complex nature of the transportation
      infrastructure and human mobility. Here we show a first-principles based method
      for traffic prediction using a cost-based generalization of the radiation model
      for human mobility, coupled with a cost-minimizing algorithm for efficient
      distribution of the mobility fluxes through the network. Using US census and
      highway traffic data, we show that traffic can efficiently and accurately be
      computed from a range-limited, network betweenness type calculation. The model
      based on travel time costs captures the log-normal distribution of the traffic
      and attains a high Pearson correlation coefficient (0.75) when compared with real
      traffic. Because of its principled nature, this method can inform many
      applications related to human mobility driven flows in spatial networks, ranging
      from transportation, through urban planning to mitigation of the effects of
      catastrophic events. 

PMID- 25373438
TI  - Low-molecular-weight heparin to prevent postpartum venous thromboembolism. A
      pilot randomised placebo-controlled trial.
AB  - The risk of venous thromboembolism (VTE) is elevated in the postpartum period.
      Low-molecular-weight heparin (LMWH) reduces the risk of VTE in many settings but
      is costly, inconvenient and increases bleeding. Randomised controlled trials
      (RCT) are required to determine if LMWH prophylaxis provides a clinical benefit
      in high-risk postpartum women. We sought to determine if a placebo-controlled RCT
      was feasible. We conducted a multi-national, double-blind pilot RCT in "high
      risk" postpartum women comparing 21 days of prophylactic dose LMWH to identical
      saline placebo injections. The primary pilot outcome was mean number of recruited
      women per centre per month. The planned primary outcome for the full trial was
      symptomatic objectively confirmed VTE or asymptomatic proximal deep-vein
      thrombosis diagnosed by a screening bilateral leg vein ultrasound at day 21. In
      six centres, a total of 1,346 potentially eligible women were approached to
      participate; 968 were ineligible, leaving 378 (31.5%) eligible patients. Of
      these, only 25 (6.6%) were randomised at a rate of 0.7 per centre per month. The
      primary reasons for declining participation were to avoid study injections and
      being too overwhelmed to participate in research. None of the participants had a
      VTE during follow-up. In conclusion, despite an adequate number of eligible
      participants, our double-blind RCT design was not feasible due to a very low
      consent rate. Other experimental approaches may be necessary to generate evidence
      in this important area of research. 

PMID- 25373440
TI  - A potential novel treatment strategy: inhibition of angiogenesis and inflammation
      by resveratrol for regression of endometriosis in an experimental rat model.
AB  - The aim of our study was to evaluate the effectiveness of resveratrol in
      experimentally induced endometrial implants in rats through inhibiting
      angiogenesis and inflammation. Endometrial implants were surgically induced in 24
      female Wistar-Albino rats in the first surgery. After confirmation of
      endometriotic foci in the second surgery, the rats were divided into resveratrol
      (seven rats), leuprolide acetate (eight rats), and control (seven rats) groups
      and medicated for 21 d. In the third surgery, the measurements of mean areas and
      histopathological analysis of endometriotic lesions, VEGF, and MCP-1 measurements
      in blood and peritoneal fluid samples, and immunohistochemical staining were
      evaluated. After treatment, significant reductions in mean areas of implants (p <
      0.01) and decreased mean histopathological scores of the implants (p < 0.05),
      mean VEGF-staining scores of endometriotic implants (p = 0.01), and peritoneal
      fluid levels of VEGF and MCP-1 (p < 0.01, for VEGF and p < 0.01, for MCP-1) were
      found in the resveratrol and leuprolide acetate groups. Serum VEGF (p = 0.05) and
      MCP-1 (p = 0.01) levels after treatment were also significantly lower in the
      resveratrol and leuprolide acetate groups. Resveratrol appears to be a potential
      novel therapeutic agent in the treatment of endometriosis through inhibiting
      angiogenesis and inflammation. Further studies are needed to determine the
      optimum effective dose in humans and to evaluate other effects on reproductive
      physiology. 

PMID- 25373439
TI  - The scientific legacy of Stephen Rothman.
AB  - The year 2014 marks the centennial of events that led to the First World War
      ("the war to end all wars") following the assassination of Archduke Ferdinand of
      the crumbling Austro-Hungarian Empire. It also marks the 120th anniversary of the
      birth of Stephen Rothman and the 60th anniversary of the publication of his epic
      textbook The Physiology and Biochemistry of the Skin. In this review, we document
      our belief that Rothman had a seismic impact on moving investigative dermatology
      from a medical backwater to a scientific discipline that can hold its own with
      any other specialty.

PMID- 25373441
TI  - The role of attentional abilities in lexically guided perceptual learning by
      older listeners.
AB  - This study investigates two variables that may modify lexically guided perceptual
      learning: individual hearing sensitivity and attentional abilities. Older Dutch
      listeners (aged 60+ years, varying from good hearing to mild-to-moderate high
      frequency hearing loss) were tested on a lexically guided perceptual learning
      task using the contrast [f]-[s]. This contrast mainly differentiates between the
      two consonants in the higher frequencies, and thus is supposedly challenging for
      listeners with hearing loss. The analyses showed that older listeners generally
      engage in lexically guided perceptual learning. Hearing loss and selective
      attention did not modify perceptual learning in our participant sample, while
      attention-switching control did: listeners with poorer attention-switching
      control showed a stronger perceptual learning effect. We postulate that listeners
      with better attention-switching control may, in general, rely more strongly on
      bottom-up acoustic information compared to listeners with poorer attention
      switching control, making them in turn less susceptible to lexically guided
      perceptual learning. Our results, moreover, clearly show that lexically guided
      perceptual learning is not lost when acoustic processing is less accurate. 

PMID- 25373442
TI  - Targeted sonography using an image fusion technique for evaluation of
      incidentally detected breast lesions on chest CT: a pilot study.
AB  - BACKGROUND: With increasing use of computed tomography (CT), incidentally
      detected breast lesions are being encountered more frequently. The aim of our
      study was to verify the utility of targeted sonography using an image fusion
      technique, real-time virtual sonography (RVS) that coordinates real-time
      sonography images with previously obtained CT images using a magnetic position
      tracking system, for evaluation of incidentally detected breast lesions on chest
      CT. METHODS: Eleven lesions in 11 women with no history of breast cancer who were
      referred to our unit for assessment of breast lesions incidentally detected on CT
      were enrolled in this study. To assess the efficacy of targeted sonography using
      RVS, we analyzed the frequency of sonographic detection of incidentally detected
      breast lesions and the difference between sonography- and CT-determined
      diameters. RESULTS: Using RVS guidance, all 11 lesions were sonographically
      detected. Ten (91 %) of 11 lesions underwent sonography-guided biopsy, yielding a
      success rate of 90 % (9/10). The remaining sonography-guided biopsy failure
      lesion required surgical biopsy for definitive diagnosis; this was performed
      after RVS was used to mark CT imaging information onto the breast surface. Four
      (36 %) lesions subsequently proved to be malignant. The mean diameters provided
      by RVS were 14.9 +/- 6.7 mm for sonography and 16.8 +/- 7.5 mm for CT (p =
      0.538). CONCLUSION: Using RVS, a sonographic probe was precisely guided to the
      lesions. Our results suggest that targeted sonography using RVS is a useful
      technique for identifying incidentally detected breast lesions on chest CT.

PMID- 25373443
TI  - Efficient Conversion of Spermatogonial Stem Cells to Phenotypic and Functional
      Dopaminergic Neurons via the PI3K/Akt and P21/Smurf2/Nolz1 Pathway.
AB  - Parkinson's disease (PD) is a common neurodegenerative syndrome characterized by
      loss of midbrain dopaminergic (DA) neurons. Generation of functional dopaminergic
      (DA) neurons is of unusual significance for treating Parkinson's disease (PD).
      However, direct conversion of spermatogonial stem cells (SSCs) to functional DA
      neurons without being reprogrammed to a pluripotent status has not been achieved.
      Here, we report an efficient approach to obtain morphological, phenotypic, and
      functional DA neurons from SSCs using a specific combination of olfactory
      ensheathing cell-conditioned medium (OECCM) and several defined growth factors
      (DGF). By following the current protocol, direct conversion of SSCs (both SSC
      line and primary SSCs) to neural cells and DA neurons was demonstrated by
      expression of numerous phenotypic genes and proteins for neural cells, as well as
      cell morphological features. More significantly, SSCs-derived DA neurons acquired
      neuronal functional properties such as synapse formation, electrophysiology
      activity, and dopamine secretion. Furthermore, PI3K/Akt pathway and p21/Nolz1
      cascades were activated whereas Smurf2 was inactivated, leading to cell cycle
      exit during the conversion of SSCs into DA neurons. Collectively, this study
      could provide sufficient neural cells from SSCs for applications in the treatment
      of PD and offers novel insights into mechanisms underlying neural system
      development from the line of germ cells. 

PMID- 25373444
TI  - Structural states of the flexible catalytic loop of M. tuberculosis tyrosyl-tRNA
      synthetase in different enzyme-substrate complexes.
AB  - Tyrosyl-tRNA synthetase from Mycobacterium tuberculosis (MtTyrRS) is an enzyme
      that belongs to class I of aminoacyl-tRNA synthetases, which catalyze the
      attachment of L-tyrosine to its cognate tRNATyr in the preribosomal step of
      protein synthesis. MtTyrRS is incapable of cross-recognition and aminoacylation
      of human cytoplasmic tRNATyr, so this enzyme may be a promising target for
      development of novel selective inhibitors as putative antituberculosis drugs. As
      a class I aminoacyl-tRNA synthetase, MtTyrRS contains the HIGH-like and KFGKS
      catalytic motifs that catalyze amino acid activation with ATP. In this study, the
      conformational mobility of MtTyrRS catalytic KFGKS loop was analyzed by 100-ns
      all-atoms molecular dynamics simulations of the free enzyme and its complexes
      with different substrates: tyrosine, ATP, and the tyrosyl-adenylate intermediate.
      It was shown that in the closed state of the active site, the KFGKS loop, readily
      adopts different stable conformations depending on the type of bound substrate.
      Molecular dynamics simulations revealed that the closed state of the loop is
      stabilized by dynamic formation of two antiparallel beta-sheets at flanking ends
      which hold the KFGKS fragment inside the active center. Prevention of beta-sheet
      formation by introducing point mutations in the loop sequence results in a rapid
      (<20 ns) transition of the loop from its functional "closed" M-like structure to
      an inactive "open" O-like structure, i.e. rapid diffusion of the catalytic loop
      outside the active site. The flexibility and rapid dynamics of the wild-type aaRS
      catalytic loop structure are crucial for formation of protein-substrate
      interactions and subsequently for overall enzyme functional activity.

PMID- 25373445
TI  - Risk of malnutrition and zinc deficiency in community-living elderly men and
      women: the Tromso Study.
AB  - OBJECTIVE: Elderly people may be at particular risk of Zn deficiency due to an
      increased prevalence of malnutrition. The aim of the present study was to
      evaluate the Zn status in community-living elderly people at risk of
      malnutrition. DESIGN: Cross-sectional population-based survey. Individuals at
      risk of malnutrition were identified by the Malnutrition Universal Screening
      Tool. Zn status was assessed by measuring serum Zn. Logistic regression was
      performed to evaluate the association between the risk of malnutrition and Zn
      deficiency. SETTING: Municipality of Tromso, Norway. SUBJECTS: Random sample of
      743 men and 778 women aged 65-87 years. RESULTS: Zn deficiency was found in 10.1%
      of the participants, including 13.1% of the men and 7.3% of the women. Among the
      men and women at risk of malnutrition, 31.0% and 12.7%, respectively, had Zn
      deficiency. In a model adjusted for age, gender, serum albumin and smoking
      status, Zn deficiency was positively associated with the risk of malnutrition
      (OR=2.2; 95% CI 1.3, 3.6). CONCLUSIONS: Overall, Zn deficiency was found in one
      out of ten community-living elderly people and was associated with the risk of
      malnutrition. Our results encourage the assessment of Zn status in elderly people
      at risk of malnutrition, with a special emphasis on elderly men.

PMID- 25373446
TI  - Hyaluronan tetrasaccharide exerts neuroprotective effect and promotes functional
      recovery after acute spinal cord injury in rats.
AB  - The objective of this study was to explore the therapeutic efficiency of
      hyaluronan tetrasaccharide (HA4) treatment after spinal cord injury (SCI) in rats
      and to investigate the underlying mechanism. Locomotor functional and
      electrophysiological evaluations revealed that the behavioral function of rats in
      the HA4-treated group was significantly improved compared with the vehicle
      treated group. The expression of brain-derived neurotrophic factor (BDNF),
      vascular endothelial growth factor (VEGF), cluster determinant (CD44) and Toll
      like receptor-4 (TLR-4) was obviously upregulated in the HA4-treated group than
      that in the sham and vehicle-treated group. Furthermore, HA4 could induce BDNF
      and VEGF expression in the astrocytes in vitro. In addition, the high expression
      of BDNF and VEGF could be inhibited by blocking CD44 and TLR-4. These findings
      indicate that HA4 could be useful as a promising therapeutic agent for SCI and
      might exert the effect by interaction with the CD44 and TLR-4.

PMID- 25373447
TI  - Deformable registration of preoperative MR, pre-resection ultrasound, and post
      resection ultrasound images of neurosurgery.
AB  - PURPOSE: Sites that use ultrasound (US) in image-guided neurosurgery (IGNS) of
      brain tumors generally have three sets of imaging data: preoperative magnetic
      resonance (MR) image, pre-resection US, and post-resection US. The MR image is
      usually acquired days before the surgery, the pre-resection US is obtained after
      the craniotomy but before the resection, and finally, the post-resection US scan
      is performed after the resection of the tumor. The craniotomy and tumor resection
      both cause brain deformation, which significantly reduces the accuracy of the MR
      US alignment. METHOD: Three unknown transformations exist between the three sets
      of imaging data: MR to pre-resection US, pre- to post-resection US, and MR to
      post-resection US. We use two algorithms that we have recently developed to
      perform the first two registrations (i.e., MR to pre-resection US and pre- to
      post-resection US). Regarding the third registration (MR to post-resection US),
      we evaluate three strategies. The first method performs a registration between
      the MR and pre-resection US, and another registration between the pre- and post
      resection US. It then composes the two transformations to register MR and post
      resection US; we call this method compositional registration. The second method
      ignores the pre-resection US and directly registers the MR and post-resection US;
      we refer to this method as direct registration. The third method is a combination
      of the first and second: it uses the solution of the compositional registration
      as an initial solution for the direct registration method. We call this method
      group-wise registration. RESULTS: We use data from 13 patients provided in the
      MNI BITE database for all of our analysis. Registration of MR and pre-resection
      US reduces the average of the mean target registration error (mTRE) from 4.1 to
      2.4 mm. Registration of pre- and post-resection US reduces the average mTRE from
      3.7 to 1.5 mm. Regarding the registration of MR and post-resection US, all three
      strategies reduce the mTRE. The initial average mTRE is 5.9 mm, which reduces to
      3.3 mm with the compositional method, 2.9 mm with the direct technique, and 2.8
      mm with the group-wise method. CONCLUSION: Deformable registration of MR and pre-
      and post-resection US images significantly improves their alignment. Among the
      three methods proposed for registering the MR to post-resection US, the group
      wise method gives the lowest TRE values. Since the running time of all
      registration algorithms is less than 2 min on one core of a CPU, they can be
      integrated into IGNS systems for interactive use during surgery.

PMID- 25373448
TI  - Persistent hypertension in lupus nephritis and the associated risk factors.
AB  - Arterial hypertension (HPT) burden up to two third of systemic lupus
      erythematosus (SLE) patients and contributes to accelerated atherosclerosis and
      cardiovascular (CV) risk. We aim to determine the prevalence of HPT among lupus
      nephritis (LN) patients who were in complete remission (CR) for a minimum of 6
      months, with estimated glomerular filtration rate (eGFR) of >60 mL/min/1.73 m(2).
      This is a cross-sectional study of 64 LN patients who attended Nephrology/SLE
      Clinic at The National University of Malaysia Medical Centre (UKMMC). Persistent
      hypertension (blood pressure (BP) >=140/90 mmHg for at least two occasions), CR
      for a minimum of 6 months and eGFR of >60 mL/min/1.73 m(2) were identified.
      Univariate and multivariate analyses were performed to determine the demographic
      and disease characteristics associated with HPT. Thirty-four of them (53.1 %)
      were hypertensive. Persistent HPT was associated with disease duration, acute
      kidney injury and high BP at the onset of LN, longer duration interval to achieve
      CR, number of relapses and cyclosporine A (CyA) use. There were no associations
      between histological classes, nephrotic range proteinuria, body mass index and
      waist circumference with HPT. Factors independently associated with HPT were
      disease duration OR 1.06 [95 %CI (0.91-1.24)], longer duration interval to
      achieve CR OR 1.104 [95 %CI (1.02-1.19)], number of relapses OR 2.53 [95 % CI
      (1.01-6.3)] and CyA use OR 5.3 [95 % CI (1.14-23.9)]. The prevalence of HPT among
      LN is high despite in remission. Aggressive treatment is important to achieve
      early CR and to prevent relapses. 

PMID- 25373449
TI  - Influence of urate-lowering therapies on renal handling of uric acid.
AB  - The purpose of this study is to investigate the effect of urate-lowering
      therapies (ULTs) on renal uric acid excretion in gout patients. This prospective
      observational study involved 106 primary gout patients and 51 healthy controls.
      Gout patients received ULT with either xanthine oxidase inhibitors or the
      uricosuric agent benzbromarone. Parameters such as 24-h urinary uric acid,
      creatinine clearance, uric acid clearance, glomerular filtration load of uric
      acid, fractional excretion of uric acid, excretion of uric acid per volume of
      glomerular filtration, and urinary uric acid to urinary creatinine ratio were
      used to evaluate the pre- and post-treatment renal capacity for uric acid
      clearance in gout patients and were compared with the values in the healthy
      controls. Compared to healthy controls, gout patients had higher glomerular
      filtration load of uric acid and lower uric acid clearance, creatinine clearance,
      and fractional uric acid excretion. After ULT, both the xanthine oxidase
      inhibitor group and benzbromarone group patients showed reduction in glomerular
      filtration load of uric acid. Creatinine clearance was significantly improved in
      the xanthine oxidase inhibitor group. Excretion function was remarkably enhanced
      in patients who reached the treatment target (serum uric acid <6 mg/dl). Changes
      in glomerular uric acid filtration load were significantly correlated with
      changes in serum urate levels. Gout patients have impaired renal uric acid
      excretion. ULTs reduce renal urate load and enhance the renal capacity of uric
      acid clearance. Xanthine oxidase inhibitors showed superiority over benzbromarone
      in improving renal function. 

PMID- 25373450
TI  - Factors associated with polyp regression after intravitreal ranibizumab
      injections for polypoidal choroidal vasculopathy.
AB  - PURPOSE: To investigate the predictive factors of polyp regression after
      intravitreal ranibizumab injections for polypoidal choroidal vasculopathy (PCV).
      METHODS: Sixty-nine eyes (69 patients) with treatment-naive PCV received an
      initial series of 3-monthly intravitreal ranibizumab injections, followed by as
      needed injections. Polyp regression was determined after 6 months from baseline
      by means of indocyanine angiography and correlated with clinical characteristics
      at baseline. RESULTS: After treatment, 26.1% (18 out of 69 eyes) achieved
      complete polyp regression and 73.9% (51 out of 69 eyes) showed persistent polyps.
      The mean logarithm of the minimum angle of resolution (logMAR) of best-corrected
      visual acuity (BCVA) was significantly improved in both groups (P = 0.02). No
      statistically significant difference in BCVA improvement was observed between the
      groups. However, the proportion of subjects with BCVA improvement by more than
      three lines was significantly higher in the polyp regression group (P = 0.02).
      Univariate analysis of the baseline characteristics identified the number of
      polyps (P = 0.02), the total polyp area (P = 0.009) and the polyp pattern (P =
      0.01) as predictive factors for polyp regression. Multivariate logistic
      regression identified the total polyp area (P = 0.01) as an independent predictor
      for polyp regression after intravitreal ranibizumab injections. CONCLUSIONS: The
      regression of polypoidal lesions in PCV patients after intravitreal ranibizumab
      injections was associated with a smaller total polyp area. This result could be
      helpful in predicting polypoidal changes after ranibizumab treatment and in
      deciding the best treatment strategy for PCV patients.

PMID- 25373451
TI  - Ocular adnexal IgG4-related disease: clinical features, outcome, and factors
      associated with response to systemic steroids.
AB  - PURPOSE: The aim of this study was to investigate clinical characteristics,
      outcome, and factors associated with response to systemic administration of
      steroids in patients with ocular adnexal immunoglobulin G4 (IgG4)-related
      disease. METHODS: This was a retrospective evaluation of 11 patients with
      histopathologically verified ocular adnexal IgG4-related diseases at a medical
      center in Taiwan between January 2006 and December 2012. Clinical features and
      outcome, including serial change of serum IgG4 and clinical factors related to
      response to steroids systemically were evaluated. RESULTS: Seven men and four
      women, mean age 54.5 years and mean follow-up of 33.5 months, were evaluated.
      Elevated serum IgG4 levels (>135 mg/dl) were observed in ten patients (91%).
      Lacrimal gland involvement was noted in eight (72.7%), followed by orbit,
      extraocular muscles, and eyelids. Seven patients (63.6%) had bilateral ocular
      lesions and eight (72.7%) had extraorbital involvement. Eight of ten patients who
      underwent systemic steroid treatment responded well in the early phase.
      Recurrence developed in five patients (45%), requiring repeat steroid therapy and
      adjunctive treatment. Median serum levels of IgG4 reduced from 540 to 101 mg/dl
      in ten patients after systemic corticosteroid administration. Patients with lower
      serum IgG4 and IgG4:IgG ratio at diagnosis were associated with poor response (p
      = 0.037). CONCLUSIONS: Ocular adnexal IgG4-related disease predominantly involved
      the lacrimal glands bilaterally and was usually associated with high serum IgG4
      levels and multiple organ involvement. Most patients responded well to steroid
      therapy, which was accompanied by a marked decrease in serum IgG4.

PMID- 25373452
TI  - Synthesis of eco-friendly silver nanoparticles from Morinda tinctoria leaf
      extract and its larvicidal activity against Culex quinquefasciatus.
AB  - Mosquitoes are the major vector for the transmission of malaria, dengue fever,
      yellow fever, filariasis, chikungunya and Japanese encephalitis, and they
      accounted for global mortality and morbidity with increased resistance to common
      insecticides. The aim of this study was to investigate the larvicidal potential
      of the acetone leaf extracts of Morinda tinctoria and synthesized silver
      nanoparticles against third instar larvae of Culex quinquefasciatus Say (Diptera:
      Culicidae). Nanoparticles are being used in many commercial applications. It was
      found that aqueous silver ions can be reduced by aqueous extract of plant parts
      to generate extremely stable silver nanoparticles in water. Synthesized AgNPs
      were characterized by ultraviolet-visible (UV-vis) spectroscopy, Atomic force
      microscopy (AFM) and Fourier transform infrared spectroscopy (FT-IR) analysis.
      The synthesized silver nanoparticles have also been tested against the third
      instar larvae of C. quinquefasciatus. The leaf extract and the AgNPs high
      mortality values were 50 % lethal concentration (LC50) = 8.088 and 1.442 ppm
      against C. quinquefasciatus, respectively. The results recorded from ultraviolet
      visible spectroscopy, atomic force microscopy and Fourier transform infrared
      spectroscopy support the biosynthesis and characterization of silver
      nanoparticles. These results suggest that the leaf extract of M. tinctoria and
      synthesis of AgNPs have the potential to be used as an ideal eco-friendly
      approach for the control of C. quinquefasciatus. By this approach, it is
      suggestive that this rapid synthesis of nanoparticles would be proper for
      developing a biological process for mosquito control.

PMID- 25373454
TI  - The Alzheimer conundrum: Entanglements of dementia and aging.

PMID- 25373453
TI  - Hepatic decompensation likely attributable to simeprevir in patients with
      advanced cirrhosis.
AB  - BACKGROUND: Hyperbilirubinemia is a common side effect of protease inhibitors
      used to treat chronic hepatitis C (HCV), and most patients do not experience
      without clinically overt hepatotoxicity. The safety of second-wave protease
      inhibitors, including simeprevir, has not been well studied in patients with
      advanced cirrhosis. MATERIALS & METHODS: We report two cases of suspected drug
      induced liver injury leading to hepatic decompensation in patients with advanced
      HCV cirrhosis treated with the combination of simeprevir and sofosbuvir on a
      compassionate basis. Both patients developed marked hyperbilirubinemia out of
      proportion to their aminotransferases, despite clearance of hepatitis C RNA.
      RUCAM scoring was probable and possible, respectively. While other factors may
      have contributed to the liver injury, including infection and concurrent
      administration of other medications, we believe that the potentially deleterious
      hepatic effects of simeprevir on transporters or other key functional components
      were the main reason for their decompensation. CONCLUSIONS: Protease inhibitors
      should be used with caution, if at all, in patients with cirrhosis, especially in
      those with the most advanced disease. We await newer, safer, direct-acting
      antiviral therapies for such patients, especially those on our transplant list.

PMID- 25373455
TI  - Cell Processing Engineering for Regenerative Medicine : Noninvasive Cell Quality
      Estimation and Automatic Cell Processing.
AB  - The cell processing engineering including automatic cell processing and
      noninvasive cell quality estimation of adherent mammalian cells for regenerative
      medicine was reviewed. Automatic cell processing necessary for the
      industrialization of regenerative medicine was introduced. The cell quality such
      as cell heterogeneity should be noninvasively estimated before transplantation to
      patient, because cultured cells are usually not homogeneous but heterogeneous and
      most protocols of regenerative medicine are autologous system. The
      differentiation level could be estimated by two-dimensional cell morphology
      analysis using a conventional phase-contrast microscope. The phase-shifting laser
      microscope (PLM) could determine laser phase shift at all pixel in a view, which
      is caused by the transmitted laser through cell, and might be more noninvasive
      and more useful than the atomic force microscope and digital holographic
      microscope. The noninvasive determination of the laser phase shift of a cell
      using a PLM was carried out to determine the three-dimensional cell morphology
      and estimate the cell cycle phase of each adhesive cell and the mean
      proliferation activity of a cell population. The noninvasive discrimination of
      cancer cells from normal cells by measuring the phase shift was performed based
      on the difference in cytoskeleton density. Chemical analysis of the culture
      supernatant was also useful to estimate the differentiation level of a cell
      population. A probe beam, an infrared beam, and Raman spectroscopy are useful for
      diagnosing the viability, apoptosis, and differentiation of each adhesive cell.

PMID- 25373457
TI  - [Identity and cooperation].

PMID- 25373456
TI  - Copy-neutral loss of heterozygosity and chromosome gains and losses are frequent
      in gastrointestinal stromal tumors.
AB  - BACKGROUND: A KIT gain of function mutation is present in 70% of gastrointestinal
      stromal tumors (GISTs) and the wild-type (WT) allele is deleted in 5 to 15% of
      these cases. The WT KIT is probably deleted during GIST progression. We aimed to
      identify the mechanism of WT KIT loss and to determine whether other genes are
      involved or affected. METHODS: Whole-genome SNP array analyses were performed in
      22 GISTs with KIT exon 11 mutations, including 11 with WT loss, to investigate
      the mechanisms of WT allele deletion. CGH arrays and FISH were performed in some
      cases. Common genetic events were identified by SNP data analysis. The 9p21.3
      locus was studied by multiplex quantification of genomic DNA. RESULTS: Chromosome
      instability involving the whole chromosome/chromosome arm (whole C/CA) was
      detected in 21/22 cases. The GISTs segregated in two groups based on their
      chromosome number: polyGISTs had numerous whole C/CA gains (mean 23, range [9 to
      43]/3.11 [1 to 5]), whereas biGISTs had fewer aberrations. Whole C/CA losses were
      also frequent and found in both groups. There were numerous copy-neutral losses
      of heterozygosity (cnLOH) of whole C/CA in both polyGIST (7/9) and biGIST (9/13)
      groups. cnLOH were frequent on 4q, 11p, 11q, 1p, 2q, 3p and 10, and never
      involved 12p, 12q, 20p, 20q or 19q. Other genetic alterations included segmental
      chromosome abnormalities, complete bi-allelic deletions (homozygous deletions)
      and, more rarely, amplifications. Nine of 11 GISTs with homozygous KIT exon 11
      mutations had cnLOH of chromosome 4. CONCLUSION: The cnLOH of whole C/CA is a
      frequent genetic alteration in GISTs and is closely associated with homozygous
      mutations of KIT and WT allele deletion.

PMID- 25373458
TI  - Heat shock protein 27 phosphorylation in the proliferation and apoptosis of human
      umbilical vein endothelial cells induced by high glucose through the
      phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase 1/2
      pathways.
AB  - In the present study, the effect of the heat shock protein 27 (HSP27) signaling
      pathway on the proliferation and apoptosis of human umbilical vein endothelial
      cells (HUVECs) induced by high glucose (HG) was investigated. HUVEC proliferation
      in the indicated conditions was measured by the alamarBlue(r) assay. Apoptosis in
      HUVECs cultured with HG was analyzed by an Annexin V-fluorescein
      isothiocyanate/propidium iodide apoptosis detection kit. HSP27 activity was
      evaluated by western blotting with specific phospho-HSP27 antibody. HUVEC
      proliferation induced by HG was observed to be reduced by the HSP27 inhibitor
      quercetin in a concentration-dependent manner, with a concomitant increase in
      apoptosis. The phosphorylation of HSP27 induced by HG was blocked by the specific
      phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and the specific
      extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 in a
      concentration-dependent manner, with peak inhibition rates of 62.6 and 56.1%,
      respectively. LY294002 and U0126 also reduced HUVEC proliferation with a
      concomitant increase in apoptotic rate. In conclusion, HSP27 phosphorylation is
      important in mediating the proliferation and apoptosis of HUVECs induced by high
      glucose, and PI3K/Akt and ERK1/2 are important signaling pathways that contribute
      to HSP27 phosphorylation.

PMID- 25373459
TI  - Autologous platelet-rich plasma promotes proliferation and chondrogenic
      differentiation of adipose-derived stem cells.
AB  - Cartilage regeneration is a promising potential therapy for articular cartilage
      defects and adult stem cells serve a key role in regenerative medicine. Adipose
      derived stem cells (ADSCs) have been identified as an alternative source of adult
      stem cells in recent years and can be differentiated into numerous types of cell,
      including chondrocytes, adipocytes and osteoblasts. However, their clinical use
      is restricted by the proliferation of cells, and their tendency to
      dedifferentiate. Platelet-rich plasma (PRP) has recently emerged as a potential
      bioactive material to promote cell proliferation and differentiation, based on
      the release of growth factors. In the current study, the effect of autologous PRP
      on the proliferation and chondrogenic differentiation of ADSCs was examined. The
      results indicated that PRP promotes ADSC proliferation and suggested that PRP
      leads to chondrogenic differentiation of ADSCs in vitro. When co-cultured with
      chondrocytes, the ADSCs on three-dimensional PRP scaffolds were able to form
      neocartilage, with positive staining of safranine O, which indicated the
      production of glycosaminoglycan, and type II collagen.

PMID- 25373460
TI  - miR-107 promotes the erythroid differentiation of leukemia cells via the
      downregulation of Cacna2d1.
AB  - microRNAs (miRNAs) have been reported to be involved in various human diseases.
      They may have uses in diagnosis and as therapeutic targets, thus the discovery of
      novel miRNAs has the potential to provide clinical tools or shed light on novel
      mechanisms. In the current study, miR-107 was revealed to be downregulated in
      chronic myeloid leukemia cells. Overexpression of miR-107 in K562 and KCL-22
      chronic myeloid leukemia cells promotes erythroid differentiation, while having
      no effect on cell proliferation. Further bioinformatics predicted that one target
      of miR-107 may be Cacna2d1, a calcium channel protein. A luciferase reporter
      assay and quantitative polymerase chain reaction were utilized to confirm that
      Cacna2d1 is a target molecule of miR-107. The effect of miR-107 on K562 and KCL
      22 cells was mediated through the downregulation of Cacna2d1, as rescued
      expression of Cacna2d1 reversed the effects of miR-107. In summary, the current
      study identified a novel miRNA that is involved in chronic myeloid leukemia cell
      erythroid differentiation and the associated mechanisms, making it a potential
      therapeutic target in the treatment of chronic myeloid leukemia. 

PMID- 25373461
TI  - Prevalence and incidence of amyotrophic lateral sclerosis in Japan.
AB  - BACKGROUND: Previous studies have reported a high incidence of amyotrophic
      lateral sclerosis (ALS) in endemic foci in the Kii Peninsula, Japan. However,
      little is known about the ALS frequency in the whole country. Furthermore, the
      presence of ethnic variation in the incidence of ALS remains unknown. METHODS: We
      conducted a nationwide survey of ALS frequency in 2013 to estimate its annual
      prevalence and incidence. ALS was diagnosed based on the El Escorial Criteria.
      The study period was the 2009 fiscal year, from April 2009 to March 2010. To
      compare the incidence of ALS among prefectures, standardized incidence ratios
      (SIRs) and 95% confidence intervals (CIs) were calculated under the assumption of
      Poisson distribution. RESULTS: The annual crude prevalence and incidence rates
      per 100 000 people per year were 9.9 (95% CI 9.7-10.1) and 2.2 (95% CI 2.1-2.3),
      respectively. The age group with the highest prevalence as well as incidence was
      70-79 years, and the male-female ratio was approximately 1.5. The annual
      incidence rate adjusted for age and sex using the 2000 U.S. standard population
      was 2.3 (95% CI 2.2-2.4) per 100 000 people. Some prefectures had significantly
      high SIRs: Okinawa, Nara and Wakayama in the Kii Peninsula, and Niigata for
      males; Kumamoto for females. CONCLUSIONS: This is the first report on the annual
      prevalence and incidence of ALS in the representative population of Japan. We
      identified some prefectures with a high incidence of ALS. However, the incidence
      of ALS in the Japanese population was much lower than in the Caucasian
      populations of Europe and North America.

PMID- 25373462
TI  - Reliability of the strengths and difficulties questionnaire in Japanese preschool
      children aged 4-6 years.
AB  - BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) has been widely
      used as a brief behavioral screening. The aim of this study was to examine the
      internal consistency and test-retest reliability of the 3- to 4-year-old version
      of the SDQ (SDQ 3-4) in Japanese preschool children. METHODS: The SDQ 3-4 was
      administered to 754 parents who had 4- to 6-year-old children attending
      kindergartens or childcare centers in Wako City, Japan, at 2 different times
      (Time 1 and Time 2) over a 2-week interval between June and July 2012. Cronbach's
      alpha and correlation coefficients were used to examine internal consistency and
      test-retest reliability, respectively. RESULTS: Of 393 parents who returned their
      responses at Time 1 (response rate 52.1%), 383 were used for analysis after
      excluding 10 responses with missing data. Their children's mean age was 4.7
      (standard deviation 0.7) years. The internal consistency (Cronbach's alpha) was
      good for the total difficulties score (0.74) and the prosocial behavior scale
      (0.70). However, it was slightly worse for the emotional symptoms, conduct
      problems, and hyperactivity scales (0.61-0.66) and poor for the peer problems
      scale (0.45). Of the 383 included respondents at Time 1, 211 parents returned
      their responses at Time 2 (response rate: 55.1%). Test-retest reliability
      (correlation coefficients) was good (0.73-0.82), except for the peer problems
      scale (0.58). CONCLUSIONS: The results support the reliability of the SDQ 3-4
      being satisfactory for the total difficulties score and prosocial behavior scale
      and being acceptable for the emotional symptoms, conduct problems, and
      hyperactivity scales in Japanese preschool children aged 4-6 years.

PMID- 25373464
TI  - Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic
      Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend
      Analysis.
AB  - OBJECTIVE: To assess whether palliative primary tumor resection in colorectal
      cancer patients with incurable stage IV disease is associated with improved
      survival. BACKGROUND: There is a heated debate regarding whether or not an
      asymptomatic primary tumor should be removed in patients with incurable stage IV
      colorectal disease. METHODS: Stage IV colorectal cancer patients were identified
      in the Surveillance, Epidemiology, and End Results database between 1998 and
      2009. Patients undergoing surgery to metastatic sites were excluded. Overall
      survival and cancer-specific survival were compared between patients with and
      without palliative primary tumor resection using risk-adjusted Cox proportional
      hazard regression models and stratified propensity score methods. RESULTS:
      Overall, 37,793 stage IV colorectal cancer patients were identified. Of those,
      23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients
      undergoing palliative primary cancer resection decreased from 68.4% in 1998 to
      50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score
      matching primary cancer resection was associated with a significantly improved
      overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI)
      = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI
      = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection
      persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47
      for both overall and cancer-specific survival. CONCLUSIONS: On the basis of this
      population-based cohort of stage IV colorectal cancer patients, palliative
      primary tumor resection was associated with improved overall and cancer-specific
      survival. Therefore, the dogma that an asymptomatic primary tumor never should be
      resected in patients with unresectable colorectal cancer metastases must be
      questioned.

PMID- 25373465
TI  - Assessing Awareness and Implementation of a Recommendation for Surgical
      Innovation Committees: A Survey of Academic Institutions.
AB  - OBJECTIVE: In 2008, a Position Statement of the Society of University Surgeons
      (SUS) recommended the creation of institutional surgical innovation committees
      (SICs) to ensure appropriate oversight of surgical innovations. The purpose of
      this study was to determine the level of awareness of the position statement, and
      how innovations are handled in academic departments of surgery. METHODS: An
      electronic survey was designed to determine the level of awareness of the SUS
      recommendations among members of the Society of Surgical Chairs; the existence
      and characteristics of SICs; and alternative means of oversight of surgical
      innovations. RESULTS: The survey was distributed to 150 persons, and 65 (43%)
      surveys were returned; 84% reported their institution promoted innovative surgery
      as a strength, but 55% were unaware of the SUS recommendations; 23% reported that
      their institution has an SIC, and 20% said their institution has discussed or
      plans an SIC. Existing SICs have a median of 7 members; 57% reviewed 3 or fewer
      procedures in the prior year; and only 7% reviewed 10 or more. The majority of
      respondents reported alternative mechanisms of oversight, including
      morbidity/mortality conferences (88%), peer review (77%), and outcomes registries
      (51%). CONCLUSIONS: A minority of Surgery Department Chairs is aware of the SUS
      Position Statement. Although most reported surgical innovation was an
      institutional strength, only 23% had an SIC and most rely on other mechanisms of
      oversight. It is unclear whether academic surgical departments are committed to
      providing education and awareness of the appropriate development and
      implementation of surgical innovations.

PMID- 25373467
TI  - Pretest variables that improve the predictive value of exercise testing in women.
AB  - AIM: Graded exercise testing (GXT) is used in coronary artery disease (CAD)
      prevention and rehabilitation programs. In women, this test has a decreased
      accuracy and predictive value but there are few studies that examine the
      predictors of a verified positive test. The aim of this study was to determine
      those pretest variables that might enhance the predictive value of the GXT in
      women clients. METHODS: Medical records of 1761 patients referred for GXT's over
      a 5 yr period of time were screened. Demographic, medical, and exercise test
      variables were analyzed. The GXT's of 403 women were available for inclusion and
      they were stratified into 3 groups: positive responders that were subsequently
      shown to have CAD (N.=28 verified positive [VP]), positive responders that were
      not shown to have CAD (N.=84 non-verified positive [NVP]) and negative GXT
      responders (N.=291). Both univariate and a multivariate step-wise regression
      statistics were performed on this data. RESULTS: Pretest variables that
      differentiated between VP and NVP groups are: (an older age=65.8 vs. 60.2 yrs.
      P<0.05; a greater BMI=30.8 vs. 28.8 kg/m2; diabetes status or an elevated fasting
      glucose =107.4 vs. 95.2 mg/dL P<0.05; and the use of some cardiovascular
      medications. Our subsequent linear regression analysis emphasized that HDL
      cholesterol and beta blocker usage were the most predictive of a positive
      exercise test in this cohort. CONCLUSION: The American Heart Association
      recommends GXT's in women with an intermediate pretest probability of CAD. But
      there are only two clinical variables available prior to testing to make this
      probability decision: age and quality of chest pain. This study outlined that
      other pre-exercise test variables such as: BMI, blood chemistry (glucose and
      lipoprotein levels) and the use of cardiovascular medications are useful in
      clinical decision making. These pre-exercise test variables improved the
      predictive value of the GXT's in our sample.

PMID- 25373466
TI  - Identifying predictors of blood pressure control in the Lebanese population - a
      national, multicentric survey -- I-PREDICT.
AB  - BACKGROUND: Blood Pressure (BP) is not well controlled and factors that predict
      BP control are not well identified in Lebanon. Improvement of hypertension
      management requires an understanding of patients' characteristics and factors
      associated with uncontrolled BP. This national, multicentric, observational
      prospective study was designed to determine the predictors of BP control in
      patients followed up to 6 months. METHODS: I-PREDICT study was conducted on 988
      patients with newly diagnosed or uncontrolled hypertension. Socio-demographic and
      clinical characteristics were analyzed. The level of agreement between doctors'
      perceptions on BP control status and JNC VII guidelines was analyzed. RESULTS:
      The predictor associated with poor BP control was diabetes (OR = 0.17, CI = 0.10
      0.28 at month-1; OR = 0.15, CI = 0.10-0.24 at month-6). The predictors associated
      with better BP control at month-6 were the early control of BP at month-1 (OR =
      10.39, CI = 6.18-17.47) and combination therapy prescribed at baseline and month
      1 (OR = 15.14, CI = 1.09-208.46, P = 0.04). In the sub-group of diabetes, the
      predictors that were associated with better BP control at 6 months were following
      diet at V1 (OR = 2.27, CI = 1.01 to 5.12) and BP control at V2 (OR = 7.34, CT =
      3.83 to 14.07). The predictors that were associated with poor BP control at 6
      months were middle economic class (OR = 0.036, CI = 0.16-0.94) and upper economic
      class (OR = 0.036; CI = 0.13-0.93).The rate of BP control was significantly
      higher at month 6 versus month 1 (67.52% vs 44.08%, P = 0.001). Additional
      analysis showed poor agreement between the doctors' perceptions on BP control
      status and the guidelines. CONCLUSIONS: Reaching an early BP control and
      combination therapy were significant predictors of better BP control, whereas
      diabetes was a significant predictor of poor BP control. A poor agreement between
      JNC VII guidelines and clinical practice was observed. I-PREDICT study identified
      factors that can be targeted for improving BP control.

PMID- 25373468
TI  - Assessment of isokinetic knee strength in elite young female basketball players:
      correlation with vertical jump.
AB  - AIM: To explore the isokinetic concentric strength of the knee muscle groups, and
      the relationship between the isokinetic knee extensors strength and the vertical
      jump performance in young elite female basketball players. METHODS: Eighteen
      elite female basketball players performed a countermovement jump, and an
      isokinetic knee test using a Biodex dynamometer. The maximal isokinetic peak
      torque of the knee extensor and flexor muscles was recorded at four angular
      velocities (90 degrees /s, 180 degrees /s, 240 degrees /s and 300 degrees /s) for
      the dominant and non-dominant legs. The conventional hamstring/quadriceps ratio
      (H/Q) was assessed at each angular velocity for both legs. RESULTS: There was no
      significant difference between dominant and non-dominant leg whatever the angular
      velocity (all P>0.05). However, the H/Q ratio enhanced as the velocity increased
      from 180 degrees /s to 300 degrees /s (P<0.05). Furthermore, low to high
      significant positive correlations were detected between the isokinetic measures
      of the knee extensors and the vertical jump height. The highest one was found for
      the knee extensors peak torque at a velocity of 240 degrees /s (r=0.88, P<0.001).
      CONCLUSION: The results accounted for an optimal velocity at which a strong
      relationship could be obtained between isokinetic knee extensors strength and
      vertical jump height. Interestingly, the H/Q ratio of the young elite female
      basketball players in the present study was unusual as it was close to that
      generally observed in regular sportsmen.

PMID- 25373469
TI  - Reproducibility of Running Anaerobic Sprint Test for soccer players.
AB  - BACKGROUND: Although the Running Anaerobic Sprint Test (RAST) presents
      reliability when performed on firmer surfaces (i.e. athletic track), its
      application on less rigid surfaces can compromise the measure determinations.
      Thus, the aim of the present study was to evaluate the RAST reliability for
      soccer players performing on grass, and wearing soccer cleats. METHODS: Fourteen
      soccer players (16+/-1 years, 72.3+/-10.3 kg, 177.2+/-8.4 cm, 14.5+/-5.3% of fat
      mass, and VO2MAX of 52.0+/-5.1 mL?kg-1?min-1) performed six maximal 35-meter
      effort interspersed by 10s of passive rest (RAST). After 48h the RAST was
      repeated to test the reliability. The main variables analyzed were the peak power
      (PP), mean power (MP), fatigue indexes (FI), and impulse (ImP). The
      reproducibility of test and re-test was tested through the Student's t Test to
      paired samples, intraclass correlation (ICC), typical error (TE), and coefficient
      of variation (CV%). RESULTS: The PP (test=701.4+/-169.5 W; re-test 712.4+/-142.3
      W), MP (test=538.6+/-111.4 W; re-test=551.9+/-101.1 W), and the ImP
      (test=2841.2+/-461.8 N?s; re-test=2797.2+/-575.9 N?s) were not different,
      presented significant correlation between the situations (ICC=0.88; 0.96 e 0.93;
      respectively), and low values of TE (71.9 W; 30.6 W e 191.1 N?s, respectively)
      and CV% (10.2%; 5.9% e 6.8%, respectively). The FI (test=40.1+/-5.8; re
      test=38.7+/-7.7%) were not significantly related between the test and re-test,
      and presented high TE (5.7%) and CV% (14.4%). CONCLUSIONS: We can conclude that
      RAST presents high reliability when performed on grass with soccer cleats, just
      as rigid surfaces. Besides, the ImP is more robust than the.

PMID- 25373470
TI  - Acute and delayed effects of high intensity interval resistance training
      organization on cortisol and testosterone production.
AB  - BACKGROUND: The use of high-intensity interval training (HIIT) is widely diffused
      as strategy to enhance aerobic fitness and body composition. In order to offer a
      more complete training, resistance exercises have been added to HIIT (HIIRT).
      Aims of our study were to characterize both heart rate and hormonal responses
      elicited by three different protocols of HIIRT having the same exercises, the
      same load and number of repetitions for each exercise. METHODS: Eight healthy
      trained men (28.61+/-3.51 years) performed three different workouts: exercise
      order, recovery and speed of execution were differently organized according to
      workout. Salivary samples were collected before and after each workout, at 11:00
      p.m. and at 7:00 a.m. of the following day. Salive was also collected during a
      non-training day. Before and after the workout, plasma lactate was measured while
      a beat-to-beat heart rate recording was executed during each workout. Cortisol
      (C) and testosterone (T) were measured in salivary samples. RESULTS: Workouts
      elicited the same heart rate response while random organization seems to elicit
      the highest lactate, C and T increases. Also when we studied the effects of
      workouts on prolonged hormones production we observed that workout organization
      influenced post-exercise hormonal production until the following morning
      modifying their physiological trend. CONCLUSIONS: Even if exercises, load and
      number of repetitions were maintained fixed, exercise order, structured recovery
      and speed of execution determined different acute and prolonged effects. The
      knowledge of these responses is very important because may positively or
      negatively influence performance and health.

PMID- 25373471
TI  - Female athlete triad screening in Canadian Interuniversity Sport universities:
      analysis of the pre-participation evaluation form.
AB  - BACKGROUND: Our aim was to examine inclusion of screening questions related to
      female athlete triad in the Canadian Interuniversity Sport (CIS) pre
      participation evaluation (PPE) forms. We hypothesized that the current CIS PPE
      forms are not comprehensive screening tools for identifying athletes at risk for
      the female athlete triad. METHODS: All 48 English-speaking CIS universities were
      invited to participate in the study. Via e-mail, a copy of the PPE form was
      requested from team physicians and certified athletic trainers. Two reviewers
      evaluated the PPE forms for inclusion of the 12 items recommended by the Female
      Athlete Triad Coalition for primary screening for the triad. RESULTS: Thirty-nine
      of 48 CIS universities responded (81%). The majority of the universities (97%),
      required a PPE for incoming athletes. Only 9 universities (24%) had 6 or more of
      the 12 recommended screening items included in their forms, whereas 26
      universities (70%) included 4 or less items. Three universities (8%) did not
      address any of the recommended questions. Questions related to disordered eating
      were often absent in the collected PPEs. In 10 universities (27%), PPE forms were
      completed by the athlete alone. The remaining 27 (73%) universities required the
      form to be completed by the athlete in conjunction with a therapist, physician,
      or both. CONCLUSIONS: PPE forms used by CIS universities have limited ability to
      identify athletes at risk of the triad-based on the recommendations of the
      Coalition. Furthermore, there is a lack of uniformity of the PPE forms within the
      CIS.

PMID- 25373472
TI  - Image quality and dose assessment in inner ear computed tomography imaging with a
      flat panel-based system.
AB  - PURPOSE: The temporal bone includes several important structures of the human
      body, some of which are smaller than 1 mm. The aim of this study is to
      demonstrate the feasibility of a computed tomography system capable of providing
      3-dimensional images of the inner ear with low doses and a spatial resolution
      adequate for providing the surgeon with good guidance. METHODS: A laboratory
      prototype, based on a CMOS Hamamatsu model C10900D detector, was set up, and
      several tomographic tests were carried out on 2 dedicated phantoms. RESULTS: The
      proposed system is able to achieve a 150-MUm spatial resolution (5% of modulation
      transfer function) with a voxel size of 88 MUm, with an acceptable contrast and
      an estimated effective dose ranging from 1/20 up to 1/100 of the mean effective
      dose reported in literature for head computed tomography. CONCLUSION: The new
      tomographic system has shown excellent characteristics and proves suitable for
      the imaging of the inner ear. In particular, this prototype requires very low
      radiation doses.

PMID- 25373473
TI  - Primary fallopian tube carcinoma: correlation between magnetic resonance and
      diffuse weighted imaging characteristics and histopathologic findings.
AB  - OBJECTIVE: The aim of this study was to investigate the magnetic resonance (MR)
      and diffusion-weighted (DW) imaging characteristics of primary fallopian tube
      carcinoma (PFTC). METHODS: The clinical, MR, and DW imaging characteristics and
      pathologic findings of 23 patients with 27 tumors were studied retrospectively.
      The MR and DW imaging appearance of tumors including laterality, size and shape,
      architecture, signal intensity, apparent diffusion coefficient (ADC) value,
      enhancement pattern, hydrosalpinx, and intrauterine fluid collection were
      evaluated and correlated with pathologic findings. RESULTS: Histopathologically,
      all 27 tumors were serous carcinoma with a unilateral tumor in 19 patients and
      bilateral tumors in 4 patients. Thirteen patients (57%) with PFTC were
      misdiagnosed preoperatively, 10 of which as epithelial ovarian carcinoma. The
      mean (SD) largest diameter was 61 (7) mm. The tumor shape was fusiform,
      sausagelike, or serpentine in 19 patients (70%) and nodular or irregular in 8
      patients (30%). Twenty (74%) of the 27 tumors were solid, and 7 (26%) were cystic
      solid. The solid components showed hypointensity to isointensity on T1-weighted
      imaging, and isointensity to slight hyperintensity on T2-weighted imaging. There
      were obvious hyperintensity on DW imaging; obvious hypointensity on ADC maps with
      a mean (SD) ADC value of 0.79 (0.22) * 10 mm; and mild (8/27, 30%), moderate
      (13/27, 48%), and marked (6/27, 22%) enhancement on contrast-enhanced imaging.
      Ipsilateral hydrosalpinx, intrauterine fluid collection, and ascites were found
      in 14 tumors (52%) and 7 (30%) and 5 (22%) patients, respectively. CONCLUSIONS:
      The PFTC has some characteristic MR imaging features. The DW imaging, ADC maps,
      and ADC values are helpful for the detection and differentiation of PFTC from
      other pelvic masses.

PMID- 25373474
TI  - Modeling and simulation of the exposure-response and dropout pattern of
      guanfacine extended-release in pediatric patients with ADHD.
AB  - Guanfacine extended-release (GXR) is a selective alpha2A-adrenergic receptor
      agonist approved in the United States for once-daily administration for the
      treatment of attention-deficit hyperactivity disorder (ADHD) in children and
      adolescents ages 6-17 years old either as monotherapy or adjunctive to stimulant
      medications. This analysis integrates exposure-response, placebo, and dropout
      data from 10 clinical trials that used GXR in adolescents and children with ADHD.
      In these trials, the ADHD Rating Scale-IV (ADHD RS-IV) score was collected
      longitudinally within patients over the course of 6-13 weeks. Non-linear mixed
      effects models were developed and used to describe the exposure-response of the
      GXR and placebo time course. The OpenBUGS program was utilized to describe the
      dropout time course across the trials. Placebo time course was best described by
      an inverse Bateman function with a 3-group mixture model that allowed for the
      onset and offset of the placebo response. Dropout time modeling indicated a
      missing at random mechanism for dropouts which was best described by a Weibull
      distribution with an estimated percentage of non-dropout patients. A linear
      exposure-response model with an adolescent effect on maximum slope (SLPmax), and
      a time delay for reaching SLPmax, provided the best description of the GXR
      exposure-response time course. The GXR exposure-response model indicated that the
      typical (95 % confidence interval) decrease in ADHD RS-IV score from the placebo
      response trajectory would be 37.1 % (32.2, 42.0 %) per 0.1 mg/kg of GXR exposure.
      There was little noticeable difference between the exposure-response in
      adolescents and children or across ADHD subtypes.

PMID- 25373475
TI  - Vangl2 regulates E-cadherin in epithelial cells.
AB  - E-cadherin belongs to the classic cadherin subfamily of calcium-dependent cell
      adhesion molecules and is crucial for the formation and function of epithelial
      adherens junctions. In this study, we demonstrate that Vangl2, a vertebrate
      regulator of planar cell polarity (PCP), controls E-cadherin in epithelial cells.
      E-cadherin co-immunoprecipitates with Vangl2 from embryonic kidney extracts, and
      this association is also observed in transfected fibroblasts. Vangl2 enhances the
      internalization of E-cadherin when overexpressed. Conversely, the quantitative
      ratio of E-cadherin exposed to the cell surface is increased in cultured renal
      epithelial cells derived from Vangl2(Lpt/+) mutant mice. Interestingly, Vangl2 is
      also internalized through protein traffic involving Rab5- and Dynamin-dependent
      endocytosis. Taken together with recent reports regarding the transport of
      Frizzled3, MMP14 and nephrin, these results suggest that one of the molecular
      functions of Vangl2 is to enhance the internalization of specific plasma membrane
      proteins with broad selectivity. This function may be involved in the control of
      intercellular PCP signalling or in the PCP-related rearrangement of cell
      adhesions. 

PMID- 25373476
TI  - An energy transfer kinetic probe for OH-quenchers in the Nd(3+):YPO4 nanocrystals
      suitable for imaging in the biological tissue transparency window.
AB  - Tetragonal xenotime-type yttrium orthophosphate (YPO4) Nd(3+) doped nanoparticles
      suitable for biomedical applications were prepared by microwave-hydrothermal
      treatment. We applied the energy transfer probing based on the analysis of
      kinetics of impurity quenching to determine the presence and spatial position of 
      OH fluorescence quenching acceptors in the impurity-containing nanoparticles. We
      show that the impurity quenching kinetics of the 0.1 at% Nd(3+) doped YPO4
      nanoparticles is a two stage (ordered and disordered) static kinetics, determined
      by a direct energy transfer to the -OH acceptors. Analyzing the ordered stage, we
      assume that the origin of the -OH groups is the protonation of the phosphate
      groups, while analyzing the disordered stage, we assume the presence of water
      molecules in the mesopores. We determine the dimension of the space of the -OH
      acceptors as d = 3 and quantify their absolute concentration using the disordered
      Forster stage of kinetics. We use the late stage of kinetics of fluorescence
      hopping (CDD ? CDA) quenching (the fluctuation asymptotics) at 1 at% Nd(3+)
      concentration as an energy transfer probe to quantify the relative concentration
      of -OH molecular groups compared to an optically active rare-earth dopant in the
      volume of NPs, when energy migration over Nd(3+) donors to the -OH acceptors
      accelerates fluorescence quenching. In doing so we use just one parameter alpha =
      gamma(A)/gamma(D) = n(A)?[C(DA)]/n(D)?[C(DD)], defined by the relation of
      concentration of the -OH acceptors to the concentration of an optically active
      dopant. The higher is the alpha, the higher is the relative concentration of -OH
      acceptors in the volume of nanoparticles. We find alpha = 2.95 for the 1 at%
      Nd(3+):YPO4 NPs that, according to the equation for alpha, and the results
      obtained for the values of the microparameters CDD(Nd-Nd) = 24.6 nm(6) ms(-1) and
      CDA(Nd-OH) = 0.6 nm(6) ms(-1), suggests twenty times higher concentration for
      acceptors other than donors. As the main result we have established that the
      majority of -OH acceptors is located not on the surface of the Nd(3+):YPO4
      nanoparticles, as many researchers assumed, but in their volume, and can be
      either associated with crystal structure defects or located in the mesopores.

PMID- 25373477
TI  - Efficient solution-processed small-molecule solar cells by insertion of graphene
      quantum dots.
AB  - In this work, we have demonstrated the results of several positive effects that
      arise from the addition of graphene quantum dots (GQDs) to solution-processed
      small molecule bulk-heterojunction (SM-BHJ) solar cells fabricated from a p
      DTS(FBTTh(2))(2)/[6,6]-phenyl C(71) butyric acid methyl-ester (PC(71)BM). The
      device with an optimized ratio of GQDs exhibits increased current density and
      fill factor owing to 10% improved external quantum efficiency (EQE) and induction
      of a favorable SM-BHJ morphology. Additionally, the multiple scattering of the
      GQDs in the SM-BHJ leads to longer optical pathlengths according to the analysis
      of diffuse reflectance spectra and UV/Vis absorption spectra. The GQD inserted SM
      BHJ film at the optimized concentration exhibits decreased charge transport
      resistance significantly by impedance measurements with effective charge
      extraction in the device which contributes to 15% enhancement of power conversion
      efficiency (PCE).

PMID- 25373478
TI  - Statistical analysis, optimization, and prioritization of virtual screening
      parameters for zinc enzymes including the anthrax toxin lethal factor.
AB  - The anthrax toxin lethal factor (LF) and matrix metalloproteinase-3 (MMP-3,
      stromelysin-1) are popular zinc metalloenzyme drug targets, with LF primarily
      responsible for anthrax-related toxicity and host death, while MMP-3 is involved
      in cancer- and rheumatic disease-related tissue remodeling. A number of in silico
      screening techniques, most notably docking and scoring, have proven useful for
      identifying new potential drug scaffolds targeting LF and MMP-3, as well as for
      optimizing lead compounds and investigating mechanisms of action. However,
      virtual screening outcomes can vary significantly depending on the specific
      docking parameters chosen, and systematic statistical significance analyses are
      needed to prioritize key parameters for screening small molecules against these
      zinc systems. In the current work, we present a series of chi-square statistical
      analyses of virtual screening outcomes for cocrystallized LF and MMP-3 inhibitors
      docked into their respective targets, evaluated by predicted enzyme-inhibitor
      dissociation constant and root-mean-square deviation (RMSD) between predicted and
      experimental bound configurations, and we present a series of preferred
      parameters for use with these systems in the industry-standard Surflex-Dock
      screening program, for use by researchers utilizing in silico techniques to
      discover and optimize new scaffolds.

PMID- 25373479
TI  - Immunopotentiation for bacterial biodefense.
AB  - Activation of the innate immune system can enhance resistance to a variety of
      bacterial and viral infections. In situations where the etiological agent of
      disease is unknown, such as a bioterror attack, stimulation of innate immunity
      may be particularly useful as induced immune responses are often capable of
      providing protection against a broad range of pathogens. In particular, the
      threat of an intentional release of a highly virulent bacterial pathogen that is
      either intrinsically resistant to antibiotics, or has been weaponized via the
      introduction of antibiotic resistance, makes immunopotentiation an attractive
      complementary or alternative strategy to enhance resistance to bacterial
      biothreat agents. Francisella tularensis, Yersinia pestis, Bacillus anthracis,
      and Burkholderia mallei or pseudomallei can all be easily disseminated via the
      respiratory route and infections can result in high mortality rates. Therefore,
      there has been a marked increase in research on immunotherapeutics against these
      Tier 1 select agents over the last 10 years that will be covered in this review.
      In addition, immunopotentiation against non-Tier 1 select agents such as Brucella
      spp., and Coxiella burnetii has also been studied and will be reviewed here. In
      particular, we will focus on cellular targets, such as toll-like receptors
      (TLRs), carbohydrate receptors and cytokine receptors, which have been exploited
      by immunomodulatory regimens that confer broad-spectrum protection against
      virulent bacterial pathogens.

PMID- 25373480
TI  - Histone Methyltransferase hSETD1A Is a Novel Regulator of Metastasis in Breast
      Cancer.
AB  - Epigenetic alteration is a hallmark of all cancers. Such alterations lead to
      modulation of fundamental cancer-related functions, such as proliferation,
      migration, and invasion. In particular, methylation of Histone H3 Lysine 4
      (H3K4), a histone mark generally associated with transcriptional activation, is
      altered during progression of several human cancers. While the depletion of H3K4
      demethylases promotes breast cancer metastasis, the effect of H3K4
      methyltransferases on metastasis is not clear. Nevertheless, gene duplications in
      the human SETD1A (hSETD1A) H3K4 methyltransferase are present in almost half of
      breast cancers. Herein, expression analysis determined that hSETD1A is
      upregulated in multiple metastatic human breast cancer cell lines and clinical
      tumor specimens. Ablation of hSETD1A in breast cancer cells led to a decrease in
      migration and invasion in vitro and to a decrease in metastasis in nude mice.
      Furthermore, a group of matrix metalloproteinases (including MMP2, MMP9, MMP12,
      MMP13, and MMP17) were identified which were downregulated upon depletion of
      hSETD1A and demonstrated a decrease in H3K4me3 at their proximal promoters based
      on chromatin immunoprecipitation analysis. These results provide evidence for a
      functional and mechanistic link among hSETD1A, MMPs, and metastasis in breast
      cancer, thereby supporting an oncogenic role for hSETD1A in cancer. IMPLICATIONS:
      This study reveals that hSETD1A controls tumor metastasis by activating MMP
      expression and provides an epigenetic link among hSETD1A, MMPs, and metastasis of
      breast cancer.

PMID- 25373481
TI  - Strength Asymmetry and Landing Mechanics at Return to Sport after Anterior
      Cruciate Ligament Reconstruction.
AB  - PURPOSE: Evidence-based quadriceps femoris muscle (QF) strength guidelines for
      return to sport after anterior cruciate ligament (ACL) reconstruction are
      lacking. This study investigated the effect of QF strength asymmetry on knee
      landing biomechanics at the time of return to sport after ACL reconstruction.
      METHODS: Seventy-seven individuals (17.4 yr) at the time of return to sport after
      primary ACL reconstruction (ACLR group) and 47 uninjured control individuals
      (17.0 yr; CTRL group) participated. QF strength was assessed and quadriceps index
      was calculated (QI = [involved strength / uninvolved strength] * 100%). The ACLR
      group was subdivided based on QI: high quadriceps (HQ, QI >= 90%) and low
      quadriceps (LQ, QI < 85%). Knee kinematic and kinetic variables were collected
      during a drop vertical jump maneuver. Limb symmetry during landing and discrete
      variables were compared among the groups using multivariate analysis of variance
      and linear regression analyses. RESULTS: The LQ group demonstrated worse
      asymmetry in all kinetic and ground reaction force variables compared to the HQ
      and CTRL groups, including reduced involved limb peak knee external flexion
      moments (P < 0.001), reduced involved limb (P = 0.003) and increased uninvolved
      limb (P = 0.005) peak vertical ground reaction forces and higher uninvolved limb
      peak loading rates (P < 0.004). There were no differences in the landing patterns
      between the HQ and CTRL groups on any variable (P > 0.05). In the ACLR group, QF
      strength estimated limb symmetry during landing after controlling for graft type,
      meniscus injury, knee pain, and symptoms. CONCLUSIONS: At the time of return to
      sport, individuals after ACL reconstruction with weaker QF demonstrate altered
      landing patterns. Conversely, those with nearly symmetrical QF strength
      demonstrate landing patterns similar to uninjured individuals. Consideration of
      an objective QF strength measure may aid clinical decision making to optimize
      sports participation after ACL reconstruction.

PMID- 25373482
TI  - Response of Bone Turnover Markers and Cytokines to High-Intensity Low-Impact
      Exercise.
AB  - INTRODUCTION: Low-impact, high-intensity interval exercise (HIE) was used to
      investigate the postexercise response in bone turnover markers and cytokines.
      METHODS: Twenty-three recreationally active males (21.8 +/- 2.4 yr) performed one
      HIE bout on a cycle ergometer at 90% maximum workload. The total duration of the
      exercise was 12 min and included six 1-min high-intensity exercise intervals
      separated by 1-min rest intervals. Blood samples were collected before exercise,
      5 min, 1 h, and 24 h after exercise and were analyzed for serum levels of anti-
      and pro-inflammatory cytokines (interleukin 10 [IL-10], interleukin 6 [IL-6],
      interleukin 1-alpha [IL-1alpha], interleukin 1-beta [IL-1beta], and tumor
      necrosis factor alpha [TNF-alpha]) and markers of bone formation (bone alkaline
      phosphatase [BAP], osteoprotegerin [OPG]) and resorption (amino-terminal cross
      linking propeptide [NTX], receptor activator of NF-kappaB ligand [RANKL]).
      RESULTS: There was a significant (P < 0.05) time effect for all bone turnover
      markers. Post hoc analysis showed that BAP, OPG, and RANKL significantly
      increased from baseline to 5 min after exercise (10.9%, 13.5%, and 34.2%, P <
      0.05). At 1 h after exercise, only BAP was significantly higher than baseline
      (9.5%, P = 0.010) and remained higher than baseline at 24 h (10.9%, P = 0.001).
      NTX was significantly lower than baseline 24 h after exercise (-14.6%, P =
      0.046). Significant (P < 0.05) time effects were also observed for IL-1alpha, IL
      1beta, IL-6, and TNF-alpha, with all four significantly increasing 5 min after
      exercise and returning to baseline levels 1 h after exercise. The postexercise
      changes in bone formation markers correlated positively with the anti
      inflammatory cytokine (IL-10) and negatively with the pro-inflammatory cytokines
      while NTX correlated positively with a pro-inflammatory cytokine, TNF-alpha (P <
      0.05). CONCLUSIONS: These results suggest that HIE stimulates a response in bone
      turnover markers and cytokines and that a correlation exists between immune and
      skeletal responses to this form of exercise. This type of exercise may benefit
      individuals for whom high-impact exercise might be contraindicated.

PMID- 25373483
TI  - Intramuscular Fat Infiltration Contributes to Impaired Muscle Function in COPD.
AB  - Muscle weakness is a prevalent complication in chronic obstructive pulmonary
      disease (COPD). Atrophy does not fully explain muscle weakness in this
      population. The recent focus on fat infiltration and its clinical implications in
      age and diseased muscles are important because it may further explain the extent
      of declining muscle strength and mobility seen in COPD. PURPOSE: The objectives
      of this study are to quantify fat infiltration (muscle quality) of lower-limb
      muscles in people with COPD and healthy older adults using magnetic resonance
      imaging and proton magnetic resonance spectroscopy, and to explore its
      relationship with muscle strength and walking capacity in COPD. METHODS: T1
      weighted magnetic resonance imaging and proton magnetic resonance spectroscopy
      were performed in people with COPD (n = 10) and control subjects (n = 10) matched
      for age, gender, and body mass index. Maximal cross-sectional area (muscle size),
      isokinetic and isometric muscle peak torques, and 6-min walk distance were also
      assessed. RESULTS: In addition to muscle atrophy (mean between-group differences
      of 20% to 25%, P < 0.05), COPD group presented with fatty infiltration in thigh
      and calf muscles that were significantly greater than what was observed in their
      healthy counterparts (mean between-group differences of 74% to 89%, P = 0.001).
      There was a strong inverse correlation between intramuscular fat infiltration,
      muscle peak torque, and walking distance (r = -0.6 to -0.8, P < 0.001) in this
      group as opposed to fair-to-moderate correlations between muscle size and the
      same outcomes (r = 0.4-0.6, P < 0.01). CONCLUSION: Poor muscle quality
      accompanies atrophy in people with COPD. Intramuscular fat infiltration not only
      appears to have a strong correlation with impaired function but also is more
      profound than muscle atrophy in this group. Monitoring both muscle size and
      quality may enable a more comprehensive assessment of exercise programs in COPD.

PMID- 25373484
TI  - Sources of Variability in Performance Times at the World Orienteering
      Championships.
AB  - PURPOSE: An improvement equal to 0.3 of the typical variation in an elite
      athlete's race-to-race performance estimates the smallest worthwhile enhancement,
      which has not yet been determined for orienteers. Moreover, much of the research
      in high-performance orienteering has focused on physical and cognitive aspects,
      although course characteristics might influence race performance. Analysis of
      race data provides insights into environmental effects and other aspects of
      competitive performance. Our aim was to examine such factors in relation to World
      Orienteering Championships performances. METHODS: We used mixed linear modelling
      to analyze finishing times from the three qualification rounds and final round of
      the sprint, middle-distance, and long-distance disciplines of World Orienteering
      Championships from 2006 to 2013. Models accounted for race length, distance
      climbed, number of controls, home advantage, venue identity, round (qualification
      final), athlete identity, and athlete age. RESULTS: Within-athlete variability
      (coefficient of variation, mean +/- SD) was lower in the final (4.9% +/- 1.4%)
      than in the qualification (7.3% +/- 2.4%) rounds and provided estimates of
      smallest worthwhile enhancements of 1.0%-3.5%. The home advantage was clear in
      most disciplines, with distance climbed particularly impacting sprint
      performances. Small to very large between-venue differences were apparent.
      Performance predictability expressed as intraclass correlation coefficients was
      extremely high within years and was high to very high between years. Age of peak
      performance ranged from 27 to 31 yr. CONCLUSIONS: Our results suggest that elite
      orienteers should focus on training and strategies that enhance performance by at
      least 1.0%-3.5% for smallest worthwhile enhancement. Moreover, as greater
      familiarity with the terrain likely mediated the home advantage, foreign athletes
      would benefit from training in nations hosting the World Orienteering
      Championships for familiarization.

PMID- 25373485
TI  - The relationship between erythrocyte zinc levels and isotretinoin use in acne
      vulgaris patients.
AB  - BACKGROUND: Prior studies have demonstrated lower serum zinc levels in acne
      vulgaris (AV) patients compared with controls. However, no study has investigated
      the relationship between AV and erythrocyte zinc levels, which is a superior
      indicator of body zinc levels. Additionally, the potential influence of
      isotretinoin use on body zinc status remains to be evaluated. In this study, we
      aimed to determine erythrocyte zinc levels and their relationship with
      isotretinoin use in AV patients. METHODS: The enrolled study participants
      included 106 (68% female) isotretinoin-treated AV patients, 89 (65% female)
      untreated AV patients and 100 (59% female) healthy volunteers between 18 and 30
      years of age. The acne severity of the AV patients who did not receive treatment
      was assessed using the classification system of the International Consensus
      Conference on Acne. Erythrocyte zinc levels were analysed by atomic absorption
      spectroscopy. RESULTS: No significant differences were observed among the three
      groups with respect to erythrocyte zinc levels. In addition, erythrocyte zinc
      levels did not vary according to the severity of AV, nor according to the
      duration of isotretinoin use. CONCLUSION: This study suggests that no
      relationships exist among zinc status, AV and isotretinoin use. However, given
      the relationship between vitamin A and zinc, and the fact that previous studies
      have indicated low serum zinc levels in AV patients, prospective studies are
      required to corroborate our data.

PMID- 25373486
TI  - Intravitreal administration of known phototoxicants in the rabbit fails to
      produce phototoxicity: implications for phototoxicity testing of intravitreally
      administered small molecule therapeutics.
AB  - CONTEXT: Intravitreal (ITV) dosing has become a clinically important route of
      administration for the treatment of uveitis, endophthalmitis, retinal vein
      occlusion, diabetic macular edema and age-related macular degeneration. Despite
      this, there are no validated non-clinical models of phototoxicity for ITV
      products. OBJECTIVE: The objective of this study was to develop an ITV rabbit
      model of phototoxicity for use in assessing the photosafety of small molecules
      therapeutics. MATERIALS AND METHODS: Dutch Belted rabbits were intravitreally
      injected bilaterally with four known phototoxicants: 8-methoxypsoralen,
      lomefloxacin, doxycycline and stannsoporfrin. Triescence((r)), a non-phototoxic
      triamcinolone acetonide steroid formulation designed for ITV administration, was
      used as a negative control. One eye was then irradiated with solar-simulated
      ultraviolet radiation for 30 min, 1 h after dosing, while the other eye was
      occluded, serving as a non-irradiated control. RESULTS: Despite the direct
      administration of known phototoxicants into the vitreous, no evidence of ocular
      phototoxicity was observed in any dose group. Direct (non-phototoxic) retinal
      toxicity was observed in the doxycycline dose group only. CONCLUSION: These data
      suggest that the posterior segment of the rabbit eye is protected against
      phototoxicity by anatomical and/or physiological mechanisms, and is not a useful
      model for the assessment of phototoxicity of intravitreally administered
      molecules.

PMID- 25373487
TI  - Construction of N-containing heterocycles via oxidative intramolecular N-H/X-H
      coupling.
AB  - The preparation of N-containing heterocycles is always the core of synthetic
      chemistry. Recently, oxidative coupling between two R-H nucleophiles is gaining
      more attention due to its atom-economy and step-economy, thus there are numerous
      reports focusing on the N-heterocycle construction via oxidative coupling. This
      feature article is going to cover the methodology related to the construction of
      N-heterocycles through oxidative intramolecular N-H/X-H coupling. 

PMID- 25373488
TI  - Chiral recognition with a benzofuran receptor that mimics an oxyanion hole.
AB  - A new chiral benzofuran receptor has been synthesized and its properties in the
      association of amino acid derivatives have been studied. X-ray structures were
      obtained and these corroborate the presence of an oxyanion-hole motif in these
      structures. 

PMID- 25373489
TI  - Targeted delivery of adipocytokines into the heart by induced adipocyte cell
      sheet transplantation yields immune tolerance and functional recovery in
      autoimmune-associated myocarditis in rats.
AB  - BACKGROUND: Clinical prognosis is critically poor in fulminant myocarditis, while
      it's initiation or progression is fated, in part, by T cell-mediated
      autoimmunity. Adiponectin (APN) and associated adipokines were shown to be immune
      tolerance inducers, although the clinically relevant delivery method into target
      pathologies is under debate. Whether the cell sheet-based delivery system of
      adipokines might induce immune tolerance and functional recovery in experimental
      autoimmune myocarditis (EAM) was tested. METHODS AND RESULTS: Scaffold-free
      induced adipocyte cell-sheet (iACS) was generated by differentiating adipose
      tissue-derived syngeneic stromal vascular-fraction cells into adipocytes on
      temperature-responsive dishes. Rats with EAM underwent iACS implantation or sham
      operation. Supernatants of iACS contained a high level of APN and hepatocyte
      growth factor (HGF), and reduced proliferation of CD4-positive T cells in vitro.
      Immunohistolabelling showed that the iACS implantation elevated the levels of APN
      and HGF in the myocardium compared to the sham operation, which attenuated the
      immunological response by inhibiting CD68-positive macropharges and CD4-positive
      T-cells and activating Foxp3-positive regulatory T cells. Consequently, left
      ventricular ejection fraction was significantly greater after the iACS
      implantation than after the sham operation, in association with less collagen
      accumulation. CONCLUSIONS: The targeted delivery of adipokines using tissue
      engineered iACS ameliorated cardiac performance of the EAM rat model via effector
      T cell suppression and induction of immune tolerance. These findings might
      suggest a potential of this tissue-engineered drug delivery system in treating
      fulminant myocarditis in the clinical setting.

PMID- 25373490
TI  - Maspin expression in prostate tumor elicits host anti-tumor immunity.
AB  - The goal of the current study is to examine the biological effects of epithelial
      specific tumor suppressor maspin on tumor host immune response. Accumulated
      evidence demonstrates an anti-tumor effect of maspin on tumor growth, invasion
      and metastasis. The molecular mechanism underlying these biological functions of
      maspin is thought to be through histone deacetylase inhibition, key to the
      maintenance of differentiated epithelial phenotype. Since tumor-driven stromal
      reactivities co-evolve in tumor progression and metastasis, it is not surprising
      that maspin expression in tumor cells inhibits extracellular matrix degradation,
      increases fibrosis and blocks hypoxia-induced angiogenesis. Using the athymic
      nude mouse model capable of supporting the growth and progression of xenogeneic
      human prostate cancer cells, we further demonstrate that maspin expression in
      tumor cells elicits neutrophil- and B cells-dependent host tumor immunogenicity.
      Specifically, mice bearing maspin-expressing tumors exhibited increased systemic
      and intratumoral neutrophil maturation, activation and antibody-dependent
      cytotoxicity, and decreased peritumoral lymphangiogenesis. These results reveal a
      novel biological function of maspin in directing host immunity towards tumor
      elimination that helps explain the significant reduction of xenograft tumor
      incidence in vivo and the clinical correlation of maspin with better prognosis of
      several types of cancer. Taken together, our data raised the possibility for
      novel maspin-based cancer immunotherapies. 

PMID- 25373491
TI  - Effects of PI3Kgamma overexpression in the hippocampus on synaptic plasticity and
      spatial learning.
AB  - Previous studies have shown that a family of phosphoinositide 3-kinases (PI3Ks)
      plays pivotal roles in the brain; in particular, we previously reported that
      knockout of the gamma isoform of PI3K (PI3Kgamma) in mice impaired synaptic
      plasticity and reduced behavioral flexibility. To further examine the role of
      PI3Kgamma in synaptic plasticity and hippocampus-dependent behavioral tasks we
      overexpressed p110gamma, the catalytic subunit of PI3Kgamma, in the hippocampal
      CA1 region. We found that the overexpression of p110gamma impairs NMDA receptor
      dependent long-term depression (LTD) and hippocampus-dependent spatial learning
      in the Morris water maze (MWM) task. In contrast, long-term potentiation (LTP)
      and contextual fear memory were not affected by p110gamma overexpression. These
      results, together with the previous knockout study, suggest that a critical level
      of PI3Kgamma in the hippocampus is required for successful induction of LTD and
      normal learning. 

PMID- 25373492
TI  - Postoperative shoulder imbalance in Lenke Type 1A adolescent idiopathic scoliosis
      and related factors.
AB  - BACKGROUNDS: The purpose of this study was to investigate the occurrence and
      factors associated with postoperative shoulder imbalance (PSI) in Lenke type 1A
      curve. METHODS: This study included 106 patients with Lenke Type 1A curve who
      were followed up more than two years after posterior correction surgery. Pedicle
      screw (PS) constructs were used in 84 patients, and hybrid constructs in 22. The
      upper instrumented vertebra was rostral to the upper-end vertebra (UEV) in 70
      patients, at UEV in 26, and below UEV in 10. The clavicle angle and T1 tilt angle
      were measured as PSI indicators, and correlations between radiographic parameters
      of shoulder balance and other radiographic parameters and associations between
      PSI and clinical parameters were investigated. For statistical analyses, paired
      and unpaired t-tests were used. RESULTS: The mean Cobb angles of the main and
      proximal thoracic curves were 54.6 +/- 9.5 and 26.7 +/- 7.9 degrees before
      surgery, 14.5 +/- 7.5, and 14.9 +/- 7.1 at follow-up. Clavicle angle and T1 tilt
      angle were -2.9 +/- 2.8 and -2.6 +/- 6.3 before surgery, 2.4 +/- 2.8 and 4.4 +/-
      4.3 immediately after surgery, and 1.8 +/- 2.1 and 3.4 +/- 5.5 at follow-up.
      Twenty patients developed distal adding-on. Clavicle angle at follow-up
      correlated weakly but significantly with preoperative clavicle angle (r = 0.34, p
      = 0.001) and with the correction rates of the main thoracic curve (r = 0.34, p =
      0.001); it correlated negatively with the proximal curve spontaneous correction
      rate (r=-0.21, p = 0.034). The clavicle angle at follow-up was significantly
      larger in patients with PS-only constructs (PS 2.1 degrees vs. hybrid 0.9, p =
      0.02), and tended to be smaller in patients with distal adding-on (adding-on 1.1
      vs. non adding-on 2.0, p = 0.09). CONCLUSIONS: PSI was more common with better
      correction of the main curve (using PS constructs), in patients with a larger
      preoperative clavicle angle, and with a larger and more rigid proximal curve.
      Distal adding-on may compensate for PSI.

PMID- 25373494
TI  - A review of finite size effects in quasi-zero dimensional superconductors.
AB  - Quantum confinement and surface effects (SEs) dramatically modify most solid
      state phenomena as one approaches the nanometer scale, and superconductivity is
      no exception. Though we may expect significant modifications from bulk
      superconducting properties when the system dimensions become smaller than the
      characteristic length scales for bulk superconductors-such as the coherence
      length or the penetration depth-it is now established that there is a third
      length scale which ultimately determines the critical size at which Cooper
      pairing is destroyed. In quasi-zero-dimensional (0D) superconductors (e.g.
      nanocrystalline materials, isolated or embedded nanoparticles), one may define a
      critical particle diameter below which the mean energy level spacing arising from
      quantum confinement becomes equal to the bulk superconducting energy gap. The so
      called Anderson criterion provides a remarkably accurate estimate of the limiting
      size for the destabilization of superconductivity in nanosystems. This review of
      size effects in quasi-0D superconductors is organized as follows. A general
      summary of size effects in nanostructured superconductors (section 1) is followed
      by a brief overview of their synthesis (section 2) and characterization using a
      variety of techniques (section 3). Section 4 reviews the size-evolution of
      important superconducting parameters-the transition temperature, critical fields
      and critical current-as the Anderson limit is approached from above. We then
      discuss the effect of thermodynamic fluctuations (section 5), which become
      significant in confined systems. Improvements in fabrication methods and the
      increasing feasibility of addressing individual nanoparticles using scanning
      probe techniques have lately opened up new directions in the study of nanoscale
      superconductivity. Section 6 reviews both experimental and theoretical aspects of
      the recently discovered phenomena of 'parity effect' and 'shell effect' that lead
      to a strong, non-monotonic size dependence of the superconducting energy gap and
      associated properties. Finally, we discuss in section 7 the properties of ordered
      heterostructures (bilayers and multilayers of alternating superconducting and
      normal phases) and disordered heterostructures (nanocomposites consisting of
      superconducting and normal phases), which are primarily controlled by the
      proximity effect.

PMID- 25373493
TI  - Profiling status epilepticus-induced changes in hippocampal RNA expression using
      high-throughput RNA sequencing.
AB  - Status epilepticus (SE) is a life-threatening condition that can give rise to a
      number of neurological disorders, including learning deficits, depression, and
      epilepsy. Many of the effects of SE appear to be mediated by alterations in gene
      expression. To gain deeper insight into how SE affects the transcriptome, we
      employed the pilocarpine SE model in mice and Illumina-based high-throughput
      sequencing to characterize alterations in gene expression from the induction of
      SE, to the development of spontaneous seizure activity. While some genes were
      upregulated over the entire course of the pathological progression, each of the
      three sequenced time points (12-hour, 10-days and 6-weeks post-SE) had a largely
      unique transcriptional profile. Hence, genes that regulate synaptic physiology
      and transcription were most prominently altered at 12-hours post-SE; at 10-days
      post-SE, marked changes in metabolic and homeostatic gene expression were
      detected; at 6-weeks, substantial changes in the expression of cell excitability
      and morphogenesis genes were detected. At the level of cell signaling, KEGG
      analysis revealed dynamic changes within the MAPK pathways, as well as in CREB
      associated gene expression. Notably, the inducible expression of several
      noncoding transcripts was also detected. These findings offer potential new
      insights into the cellular events that shape SE-evoked pathology. 

PMID- 25373495
TI  - Platinum(II) clovers targeting G-quadruplexes and their anticancer activities.
AB  - Two porphyrin-bridged tetranuclear platinum(II) complexes are found to
      effectively stabilize various kinds of G-quadruplexes. Their clover-like shape
      endows them with the capability of targeting G-quadruplexes rather than the
      double-stranded structure. Their excellent anticancer activity is the result of a
      dual effect, inhibition of the telomerase activity and repression of oncogene
      expression.

PMID- 25373496
TI  - Effect of intermaxillary tooth-size discrepancy on accuracy of prediction
      equations for mixed dentition space analysis.
AB  - AIM: Correlation-statistical methods are widely used for prediction of size of
      unerupted permanent canines and premolars in mixed dentition space analysis. The
      present study was planned to evaluate the effect of selecting dental study casts
      with no intermaxillary tooth-size discrepancy on the accuracy of predicting
      mesiodistal widths (MDWS) of permanent canines and premolars. STUDY DESIGN:
      Bolton ratios were calculated for all the screened study dental casts fulfilling
      the inclusion criteria. Subjects were divided into two groups. Group A: all
      subjects with no intermaxillary tooth-size discrepancy within +/-2 SD (Standard
      deviation) of the mean values. Group B: increased percentage of subjects with
      intermaxillary tooth-size discrepancy beyond +/-2 SD (Standard deviation) of the
      mean values. STATISTICS: Linear regression equations were established for both
      maxilla and mandible in both the groups, with different tooth combinations as
      independent variables. Validation of best possible regression equations was done
      on an independent set of 40 subjects. The actual and predicted values of MDWS of
      permanent canines and premolars were compared by paired samples t test in both
      groups, for both arches. RESULTS: The accuracy of equations derived from group A
      was higher than those derived from group B. The difference between actual and
      predicted values was statistically insignificant in group A and statistically
      significant in group B. CONCLUSION: The results confirm the accuracy of simple
      linear regression equations derived from a sample of children with no
      intermaxillary tooth-size discrepancy.

PMID- 25373498
TI  - Effects of prodigiosin family compounds from Pseudoalteromonas sp. 1020R on the
      activities of protein phosphatases and protein kinases.
AB  - Pseudoalteromonas sp. strain 1020R produces prodigiosin and its closely related
      congeners, which differ in the length of their alkyl side chains. These red
      pigmented compounds were found to exhibit cytotoxicity against human leukemia
      cell lines. The compounds also showed dose-dependent inhibitory effects on
      protein phosphatase 2A and protein tyrosine phosphatase 1B (PTP1B), while
      remaining relatively inactive against protein kinases, including protein tyrosine
      kinase, Ca(2+)/calmodulin-dependent protein kinase and protein kinases A and C.
      Comparative studies of the individual pigmented compounds on PTP1B inhibition
      showed that as the chain length of the alkyl group at the C-3 position of the
      compound increased, the inhibitory effect on PTP1B decreased. These results
      suggest that protein phosphatases but not protein kinases might be involved in
      the cytotoxicity of the prodigiosin family of compounds against malignant cells. 

PMID- 25373499
TI  - Purification and characterization of a phenoloxidase in the hemocytes of Ephestia
      kuehniella Zeller (Lepidoptera: Pyralidae): effects of insect growth regulators
      and endogenous inhibitors.
AB  - A phenoloxidase was extracted and purified from hemocytes of Ephestia kuehniella
      by using ammonium sulfate, Sepharyl G-100 and DEAE-Cellulose fast flow
      chromatographies. At the final stage of purification, a protein was purified by
      molecular mass of 78.5 kDa, specific activity of 1.17 U/mg protein, recovery of
      20.48% and purification fold of 16.71. The purified PO showed the highest
      activity at pH 4-5 and temperatures of 35-40  degrees C. Na(+), K(+), Mn(+),
      Zn(2+) and Mg(2+) decreased activity of the purified PO but Ca(2+) and Cu(2+)
      increased the enzymatic activity. EDTA (General chelating agent), DTC (Copper
      chelating agent) and EGTA (Calcium chelating agent) significantly decreased PO
      activity but TTHA (Magnesium chelating agent) showed no statistically significant
      effects. Kinetic parameters of the purified enzyme showed the highest Vmax when L
      DOPA was used as substrate but no significant differences were observed in case
      of Km for used L-DOPA, pyrocatechol and hydroquinone. In vitro inhibition of the
      purified PO by using two insect growth regulators, Hexaflumuron and Pyriproxyfen,
      revealed IC50 of 96.41 and 38.59 ug/ml for these compounds, respectively. Kinetic
      studies using different concentrations of L-DOPA and IC50 concentrations of the
      two IGRs revealed the increase of Km value versus control and competitive
      inhibition. Finally, column chromatography of hemolymph revealed peak III showing
      endogenous inhibitors of phenoloxidase by molecular weight of 27.3 that showed
      competitive inhibition on the PO.

PMID- 25373497
TI  - Toxoplasma gondii seroprevalence in wild boars (Sus scrofa) in Sweden and
      evaluation of ELISA test performance.
AB  - Toxoplasma gondii is a zoonotic protozoan parasite, infecting a wide range of
      warm-blooded animals. The Swedish wild boar population is expanding and increased
      hunting provides its meat to a growing group of consumers. We performed a spatio
      temporal investigation of T. gondii seroprevalence in Swedish wild boars. An
      ELISA was set up and evaluated against a commercial direct agglutination test,
      using Bayesian latent class analysis. The ELISA sensitivity and specificity were
      estimated to 79% and 85%, respectively. Of 1327 serum samples, 50% were positive.
      Thirty-four per cent of young wild boars and 55% of adults were positive (P <
      0.001). The total seroprevalence ranged from 72% in 2005 to 38% in 2011 (P <
      0.001), suggesting a declining trend. The highest seroprevalence, 65%, was
      recorded in South Sweden. In other regions it varied from 29% in Stockholm to 46%
      in East Middle Sweden.

PMID- 25373500
TI  - Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively
      inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII).
AB  - Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates
      including humans. A series of phenolic compounds, including guaiacol, 4
      methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde,
      catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were
      investigated for their inhibition of all the catalytically active mammalian
      isozymes of the Zn(2+)-containing CA (EC 4.2.1.1). All the phenolic compounds
      effectively inhibited human carbonic anhydrase isoenzymes (hCA I, II, IX and
      XII), with Kis in the range of 2.20-515.98 MUM. The various isozymes showed
      diverse inhibition profiles. Among the tested phenolic derivatives, compounds 4
      methyl catechol and 3-methoxy catechol showed potent activity as inhibitors of
      the tumour-associated transmembrane isoforms (hCA IX and XII) in the
      submicromolar range, with high selectivity. The results obtained from this
      research may lead to the design of more effective carbonic anhydrase isoenzyme
      inhibitors (CAIs) based on such phenolic compound scaffolds.

PMID- 25373501
TI  - A new affinity method for purification of bovine testicular hyaluronidase enzyme
      and an investigation of the effects of some compounds on this enzyme.
AB  - In this study, a new affinity gel for the purification of bovine testicular
      hyaluronidase (BTH) was synthesized. L-Tyrosine was added as the extension arm to
      the Sepharose-4B activated with cyanogen bromide. m-Anisidine is a specific
      inhibitor of BTH enzyme. m-Anisidine was clamped to the newly formed Sepharose-4B
      L-tyrosine as a ligand. As a result, an affinity gel having the chemical
      structure of Sepharose-4B-L-tyrosine-m-anisidine was obtained. BTH purified by
      ammonium sulfate precipitation and affinity chromatography was obtained with a
      16.95% yield and 881.78 degree of purity. The kinetic constants K(M) and V(Max)
      for BTH were determined by using hyaluronic acid as a substrate. K(M) and V(Max)
      values obtained from the Lineweaver-Burk graph were found to be 2.23 mM and 19.85
      U/mL, respectively. In vitro effects of some chemicals were determined on
      purified BTH enzyme. Some chemically active ingredients were 1,1-dimethyl
      piperidinium chloride, beta-naphthoxyacetic acid and gibberellic acid.
      Gibberellic acid showed the best inhibition effect on BTH.

PMID- 25373502
TI  - Stability and binding effects of silver(I) complexes at lipoxygenase-1.
AB  - An anti-inflammatory complex of Ag(I), namely [Ag(tpp)3(asp)](dmf) [tpp =
      triphenylphosphine, aspH = aspirin, dmf = N,N-dimethylformamide], was synthesized
      in an attempt to develop novel metallotherapeutic molecules. STD (1)H NMR
      experiments were used to examine if this complex binds to LOX-1. The (1)H NMR
      spectra in buffer Tris/D2O betrayed the existence of two complexes: the complex
      of aspirin and the complex of salicylic acid produced after deacetylation of
      aspirin. Nevertheless, the STD spectra showed that only the complex of salicylic
      acid is bound to the enzyme. Molecular docking and dynamics were used to
      complement our study. The complexes were stabilized inside a large LOX-1 cavity
      by establishing a network of hydrogen bonds and steric interactions. The complex
      formation with salicylic acid was more favorable. The in silico results provide a
      plausible explanation of the experimental results, which showed that only the
      complex with salicylic acid enters the binding cavity.

PMID- 25373503
TI  - A new class of quinazoline-sulfonamides acting as efficient inhibitors against
      the alpha-carbonic anhydrase from Trypanosoma cruzi.
AB  - The protozoan parasite Trypanosoma cruzi is the agent responsible for
      trypanosomiasis (Chagas disease) in humans and other animals. It has been
      recently reported that this pathogen encodes for an alpha-class carbonic
      anhydrase (CA, EC 4.2.1.1), denominated TcCA, which was shown to be crucial for
      its life cycle. Inhibition studies of a class of 4-oxoquinazoline containing a
      benzensulfonamide moiety and their 4-thioxo bioisosteres against the protozoan
      enzyme TcCA are described here. Most of 4-oxoquinazoline sulfonamides showed
      nanomolar TcCA inhibition activity with K(I)s in the same order of magnitude of
      acetazolamide (AAZ), whereas their thioxo bioisosters showed moderate anti
      Trypanosoma CA potency with K(I)s in the micromolar range. The discovery of
      compounds incorporating a 4-oxoquinazoline ring as a low-nanomolar TcCA inhibitor
      is quite promising and it may be useful for developing anti-Trypanosoma agents
      with a novel mechanism of action compared to the clinically used drugs (such as
      benznidazole, nifurtimox) for which significant resistance and serious adverse
      effects due to their high-toxicity appeared.

PMID- 25373504
TI  - Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent
      SLC2A10 missense mutations in three families with severe cardiopulmonary
      complications in infancy and a literature review.
AB  - BACKGROUND: Arterial Tortuosity Syndrome (ATS) is a very rare autosomal recessive
      connective tissue disorder (CTD) characterized by tortuosity and elongation of
      the large- and medium-sized arteries and a propensity for aneurysm formation and
      vascular dissection. During infancy, children frequently present the involvement
      of the pulmonary arteries (elongation, tortuosity, stenosis) with dyspnea and
      cyanosis. Other CTD signs of ATS are dysmorphisms, abdominal hernias, joint
      hypermobility, skeletal abnormalities, and keratoconus. ATS is typically
      described as a severe disease with high rate of mortality due to major
      cardiovascular malformations. ATS is caused by mutations in the SLC2A10 gene,
      which encodes the facilitative glucose transporter 10 (GLUT10). Approximately 100
      ATS patients have been described, and 21 causal mutations have been identified in
      the SLC2A10 gene. CASE PRESENTATION: We describe the clinical findings and
      molecular characterization of three new ATS families, which provide insight into
      the clinical phenotype of the disorder; furthermore, we expand the allelic
      repertoire of SLC2A10 by identifying two novel mutations. We also review the ATS
      patients characterized by our group and compare their clinical findings with
      previous data. CONCLUSIONS: Our data confirm that the cardiovascular prognosis in
      ATS is less severe than previously reported and that the first years of life are
      the most critical for possible life-threatening events. Molecular diagnosis is
      mandatory to distinguish ATS from other CTDs and to define targeted clinical
      follow-up and timely cardiovascular surgical or interventional treatment, when
      needed.

PMID- 25373506
TI  - Green synthesis of phosphoryl-2-oxo-2H-pyran via three component reaction of
      trialkyl phosphites.
AB  - An effective one-pot synthesis of dialkoxyphosphoryl-2-oxo-2H-pyran derivatives
      by three-component reaction of alky bromides and dialkyl acetylenedicarboxylates
      in the presence of trialkyl phosphite is described. The reactions were performed
      under solvent-free conditions at 50 degrees C and neutral conditions and provided
      good yields of products. 

PMID- 25373505
TI  - From microbial gene essentiality to novel antimicrobial drug targets.
AB  - BACKGROUND: Bacterial respiratory tract infections, mainly caused by
      Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are
      among the leading causes of global mortality and morbidity. Increased resistance
      of these pathogens to existing antibiotics necessitates the search for novel
      targets to develop potent antimicrobials. RESULT: Here, we report a proof of
      concept study for the reliable identification of potential drug targets in these
      human respiratory pathogens by combining high-density transposon mutagenesis,
      high-throughput sequencing, and integrative genomics. Approximately 20% of all
      genes in these three species were essential for growth and viability, including
      128 essential and conserved genes, part of 47 metabolic pathways. By comparing
      these essential genes to the human genome, and a database of genes from commensal
      human gut microbiota, we identified and excluded potential drug targets in
      respiratory tract pathogens that will have off-target effects in the host, or
      disrupt the natural host microbiota. We propose 249 potential drug targets, 67 of
      which are targets for 75 FDA-approved antimicrobials and 35 other researched
      small molecule inhibitors. Two out of four selected novel targets were
      experimentally validated, proofing the concept. CONCLUSION: Here we have
      pioneered an attempt in systematically combining the power of high-density
      transposon mutagenesis, high-throughput sequencing, and integrative genomics to
      discover potential drug targets at genome-scale. By circumventing the time
      consuming and expensive laboratory screens traditionally used to select potential
      drug targets, our approach provides an attractive alternative that could
      accelerate the much needed discovery of novel antimicrobials.

PMID- 25373507
TI  - Discovery of forgotten variola specimens at the National Institutes of Health in
      the USA.
AB  - In early July 2014, the National Institutes of Health in the USA discovered a few
      vials containing smallpox virus in their Bethesda, Maryland facility. The
      subsequent investigation, performed by US CDC, documented viable virus in two of
      the discovered vials that were subjected to tissue culture testing. 

PMID- 25373508
TI  - ABT-199, a BH3 mimetic that specifically targets Bcl-2, enhances the antitumor
      activity of chemotherapy, bortezomib and JQ1 in "double hit" lymphoma cells.
AB  - Double hit lymphoma (DHL) is a recently recognized lymphoma with a survival of
      less than 2 years. Both ABT-737, a Bcl-2/Bcl-XL inhibitor, and ABT-199, which
      selectively targets Bcl-2, were potently cytotoxic against DHL cell lines Sc-1
      and OcI-LY18, the RL cell line and primary human DHL cells, but not Ramos cells,
      which lack Bcl-2 expression. ABT-199 was more potent than ABT-737, and is the
      most promising of the BH3 mimetics to date. The DHL cell lines were also
      sensitive (< 200 nM) to doxorubicin, methotrexate, cytarabine and the proteosome
      inhibitor, bortezomib. The combination of chemotherapy with ABT-199 and
      doxorubicin or cytarabine, bortezomib, YM-155 and JQ1 produced synergistic cell
      kill against the DHL cell lines. Cells from a patient with DHL were also
      sensitive to JQ1 and bortezomib, providing a rationale for a clinical trial of
      these combinations in patients with relapsed DHL. 

PMID- 25373509
TI  - ETV6/ARG oncoprotein confers autonomous cell growth by enhancing c-Myc expression
      via signal transducer and activator of transcription 5 activation in the acute
      promyelocytic leukemia cell line HT93A.
AB  - We investigated the role of ETV6/ARG fusion gene by exposing the HT93A cell line
      to nilotinib. HT93A cells were cultured with or without nilotinib+/-50 ng/mL of
      granulocyte colony-stimulating factor (G-CSF). Nilotinib treatment inhibited cell
      growth by increasing the percentage of cells in G0/G1 phase through the decrease
      of phosphorylated signal transducer and activator of transcription 3 (STAT3)
      (Y705), STAT5 (Y694) and c-Myc expression. After stimulation with G-CSF, STAT5
      but not STAT3 was significantly phosphorylated in both nilotinib-treated and
      untreated cells. Moreover, combination therapy with nilotinib and G-CSF returned
      the expression level of c-Myc, cell growth and cell cycle distribution to the
      control level. These findings suggest that the ETV6/ARG oncoprotein contributes
      to autonomous cell growth by compensating for the requirement of growth factor
      through activating STAT5 signaling, which leads to the up-regulation of c-Myc.
      Our data suggest that ETV6/ARG oncoprotein is a potential target in the treatment
      of leukemia.

PMID- 25373510
TI  - Calreticulin gene mutations in the myeloproliferative neoplasms: Dameshek's other
      "myelostimulatory" factor.

PMID- 25373512
TI  - Performance of a diagnostic algorithm based on a prediction rule, D-dimer and CT
      scan for pulmonary embolism in patients with previous venous thromboembolism. A
      systematic review and meta-analysis.
AB  - Diagnostic management of suspected pulmonary embolism (PE) in patients with a
      history of venous thromboembolism (VTE) is complicated due to persistent abnormal
      D-dimer levels, residual embolic obstruction and higher clinical prediction rule
      (CPR) scores. We aimed to evaluate the safety and efficiency of the standard
      diagnostic algorithm consisting of a CPR, D-dimer test and computed tomography
      pulmonary angiography (CTPA) in this specific patient category. We performed a
      systematic literature search for prospective studies evaluating a diagnostic
      algorithm in consecutive patients with clinically suspected PE and a history of
      VTE. The VTE incidence rates during three-month follow-up and the number of
      indicated CTPAs were pooled using random effect models. Four studies concerning
      1,286 patients were included with a pooled baseline PE prevalence of 36 % (95 %
      confidence interval [CI] 30-42). In only 217 patients (15 %; 95 %CI 11-20) PE
      could be excluded without CTPA. The three-month VTE incidence rate was 0.8 % (95
      %CI 0.06-2.4) in patients managed without CTPA, 1.6 % (95 %CI 0.3-4.0) in
      patients in whom PE was excluded by CTPA and 1.4 % (95 %CI 0.6-2.7) overall. In
      the pooled studies, PE was safely excluded in patients with a history of VTE
      based on a CPR followed by a D-dimer test and/or CTPA, although the efficiency of
      the algorithm is relatively low compared to patients without a history of VTE. 

PMID- 25373513
TI  - Titania single crystals with a curved surface.
AB  - Owing to its scientific and technological importance, crystallization as a
      ubiquitous phenomenon has been widely studied over centuries. Well-developed
      single crystals are generally enclosed by regular flat facets spontaneously to
      form polyhedral morphologies because of the well-known self-confinement principle
      for crystal growth. However, in nature, complex single crystalline calcitic
      skeleton of biological organisms generally has a curved external surface formed
      by specific interactions between organic moieties and biocompatible minerals.
      Here we show a new class of crystal surface of TiO2, which is enclosed by quasi
      continuous high-index microfacets and thus has a unique truncated biconic
      morphology. Such single crystals may open a new direction for crystal growth
      study since, in principle, crystal growth rates of all facets between two normal
      {101} and {011} crystal surfaces are almost identical. In other words, the facet
      with continuous Miller index can exist because of the continuous curvature on the
      crystal surface.

PMID- 25373511
TI  - Subclass responses and their half-lives for antibodies against EBA175 and PfRh2
      in naturally acquired immunity against Plasmodium falciparum malaria.
AB  - BACKGROUND: Plasmodium falciparum EBA175 and PfRh2 belong to two main families
      involved in parasite invasion, and both are potential vaccine candidates. Current
      knowledge is limited regarding which target antigens and subclasses of antibodies
      are actually important for protection, and how naturally acquired immunity is
      achieved. METHODS: Repeated blood samples were collected from individuals in
      Nigeria over a period of almost one year. ELISA was used to analyse subclasses of
      IgG responses. RESULTS: For both EBA175 (region III-V) and (a fragment of) PfRh2,
      the dominant antibody responses consisted of IgG1 and IgG3 followed by IgG2,
      while for PfRh2 there was also a relatively prominent response for IgG4. High
      levels of IgG1, IgG2 and IgG3 for EBA175 and total IgG for PfRh2 correlated
      significantly with a lower parasitaemia during the study period. Children with
      HbAS had higher levels of some subclasses compared to children with HbAA, while
      in adults the pattern was the opposite. The half-lives of IgG2 and IgG4 against
      EBA175 were clearly shorter than those for IgG1 and IgG3. CONCLUSION: EBA175 and
      PfRh2 are potential targets for protective antibodies since both correlated with
      lower parasitaemia. The shorter half-lives for IgG2 and IgG4 might explain why
      these subclasses are often considered less important in protection against
      malaria. Triggering the right subclass responses could be of critical importance
      in a successful vaccine. Further studies are needed to evaluate the role of
      haemoglobin polymorphisms and their malaria protective effects in this process.

PMID- 25373514
TI  - Effects of caffeic acid phenethyl ester on wound healing in calvarial defects.
AB  - OBJECTIVE: The aim of this study is to analyze histologically the effect of CAPE
      on bone healing of Critical Size Defect (CSD) in rat calvaria. STUDY DESIGN:
      Thirty-two 3-month-old male rats were used. The animals were randomly divided
      into four groups. Group A received isotonic saline solution, Group B received
      CAPE (50 mmol/kg) locally, Group C received CAPE (100 mmol/kg) locally and Group
      D received CAPE (10 mmol/kg/day i.p. for 28 days) systematically. A 5-mm diameter
      calvarial defect was created in the right side of the parietal bone without
      damaging the underlying dura mater. Twenty-eight days after the surgery, all the
      animals were sacrificed. The original defect area was removed from the animal's
      calvarium bone en bloc. Beginning at the center of the surgical defect, serial
      sections of 6 um thick were cut longitudinally. The sections were stained with
      hematoxylin and eosin for analysis under a light microscope. The sections were
      analyzed for the presence of inflammatory infiltrate, connective tissue formation
      and new bone formation. Computer-assisted histomorphometic measurements were
      carried out with an automated image analysis system. RESULTS: The total new bone
      areas were significantly greater in group D than in all groups and group C was
      statistically insignificant from the other groups (p < 0.05). Group B had a
      greater, but not statistically significant (p > 0.05), amount of total
      regenerated bone area than the control group. CONCLUSION: The results indicate
      that 100 mmol/kg topical and 10 mmol/kg/day systemic application of CAPE
      increases bone healing, especially with systemic application.

PMID- 25373515
TI  - Periodontal disease as a risk factor of recurrence of venous thromboembolic
      disease: a prospective study.
AB  - BACKGROUND: In recent years, periodontal disease has been related to a large
      number of systemic disorders. OBJECTIVE: To study the possible relationship
      between periodontal disease and high levels of D-dimer in a group of patients
      with venous thromboembolic disease. MATERIALS AND METHODS: A study was made of
      142 patients diagnosed with unprovoked venous thromboembolic disease. All
      patients underwent oral examination consecutively and randomly. Finally, two
      groups were obtained: (a) patients with periodontal disease (n = 71); and (b)
      patients without periodontal disease (n = 71). All patients were subjected to
      periodontal study, with evaluation of the number of teeth, bleeding index,
      gingival index, simplified oral hygiene index, community periodontal index of
      treatment needs, clinical attachment level, probe depth, number of pockets >=4
      mm, number of pockets >=6 mm. The D-dimer values were evaluated in both groups.
      RESULTS: D-dimer values were higher in the study group than the control group,
      with statistically significant differences (p = 0.010). CONCLUSIONS: A
      relationship is observed between the presence of periodontal disease and high D
      dimer levels. Patients with venous thromboembolic disease and periodontal disease
      could have more risk of a new thromboembolism episode.

PMID- 25373516
TI  - Efficacy of ceramic repair material on the bond strength of composite resin to
      zirconia ceramic.
AB  - OBJECTIVE: The aim of this study was to evaluate the shear bond strength of
      composite resin in five different repair systems. MATERIALS AND METHODS: Sixty
      specimens (7 mm in diameter and 3 mm in height) of zirconia ceramic were
      fabricated. All specimen surfaces were prepared with a 30 um fine diamond rotary
      cutting instrument with water irrigation for 10 s and dried with oil-free air.
      Specimens were then randomly divided into six groups for the following different
      intra-oral repair systems (n = 10): Group 1, control group; Group 2, Cojet system
      (3M ESPE, Seefeld, Germany); Group 3, Cimara(r) System (Voco, Cuxhaven, Germany);
      Group 4, Z-Prime Plus System (Bisco Inc., Schaumburg, IL); Group 5, ClearfilTM
      System (Kuraray, Osaka, Japan); and Group 6, Z-Bond System (Danville, CA). After
      surface conditioning, a composite resin Grandio (Voco, Cuxhaven, Germany) was
      applied to the zirconia surface using a cylindrical mold (5 mm in diameter and 3
      mm in length) and incrementally filled up, according to the manufacturer's
      instructions of each intra-oral system. Each specimen was subjected to a shear
      load at a crosshead speed of 1 mm/min until fracture. One-way analysis of
      variance (ANOVA) and Tukey post-hoc tests were used to analyze the bond strength
      values. RESULTS: There were significant differences between Groups 2-6 and Group
      1. The highest bond strength values were obtained with Group 2 (17.26 +/- 3.22)
      and Group 3 (17.31 +/- 3.62), while the lowest values were observed with Group 1
      (8.96 +/- 1.62) and Group 6 (12.85 +/- 3.95). CONCLUSION: All repair systems
      tested increased the bond strength values between zirconia and composite resin
      that used surface grinding with a diamond bur.

PMID- 25373517
TI  - Oral health-related quality-of-life and mental health in individuals with chronic
      obstructive pulmonary disease (COPD).
AB  - OBJECTIVES: To investigate the association between oral health, oral health
      related quality-of-life (OHRQoL) and mental health-related quality-of-life (QoL)
      in persons with chronic obstructive pulmonary disease (COPD) with respect to
      demographic, social and clinical oral health variables. MATERIALS AND METHODS:
      One hundred participants were included in a cross-sectional study at a hospital
      in Norway. Data were collected via the Oral Health Impact Profile (OHIP-14), the
      SF-36v2 Health Survey Mental Component (MCS), other self-reported factors, an
      interview and a clinical examination. Multiple regression analyses were
      performed. The Regional Committee for Medical and Health Research Ethics approved
      the study. RESULTS. Higher education (p < 0.01), being a smoker (p < 0.05) and
      experience of oral health problems (p < 0.001) were significantly associated with
      oral health-related quality-of-life (OHRQoL). Furthermore, those with feelings of
      dry mouth (p < 0.05) and impaired OHRQoL (p < 0.001) experienced more mental
      health problems. CONCLUSIONS: This study demonstrated that oral health and
      personal factors are related to mental health-related QoL and OHRQoL in
      individuals with COPD. This finding shows the need to focus on oral care.

PMID- 25373518
TI  - Polysialic acid: biosynthesis, novel functions and applications.
AB  - As an anti-adhesive, a reservoir for key biological molecules, and a modulator of
      signaling, polysialic acid (polySia) is critical for nervous system development
      and maintenance, promotes cancer metastasis, tissue regeneration and repair, and
      is implicated in psychiatric diseases. In this review, we focus on the
      biosynthesis and functions of mammalian polySia, and the use of polySia in
      therapeutic applications. PolySia modifies a small subset of mammalian
      glycoproteins, with the neural cell adhesion molecule, NCAM, serving as its major
      carrier. Studies show that mammalian polysialyltransferases employ a unique
      recognition mechanism to limit the addition of polySia to a select group of
      proteins. PolySia has long been considered an anti-adhesive molecule, and its
      impact on cell adhesion and signaling attributed directly to this property.
      However, recent studies have shown that polySia specifically binds neurotrophins,
      growth factors, and neurotransmitters and that this binding depends on chain
      length. This work highlights the importance of considering polySia quality and
      quantity, and not simply its presence or absence, as its various roles are
      explored. The capsular polySia of neuroinvasive bacteria allows these organisms
      to evade the host immune response. While this "stealth" characteristic has made
      meningitis vaccine development difficult, it has also made polySia a worthy
      replacement for polyetheylene glycol in the generation of therapeutic proteins
      with low immunogenicity and improved circulating half-lives. Bacterial
      polysialyltransferases are more promiscuous than the protein-specific mammalian
      enzymes, and new studies suggest that these enzymes have tremendous therapeutic
      potential, especially for strategies aimed at neural regeneration and tissue
      repair.

PMID- 25373519
TI  - The cost and cost-effectiveness of gender-responsive interventions for HIV: a
      systematic review.
AB  - INTRODUCTION: Harmful gender norms and inequalities, including gender-based
      violence, are important structural barriers to effective HIV programming. We
      assess current evidence on what forms of gender-responsive intervention may
      enhance the effectiveness of basic HIV programmes and be cost-effective. METHODS:
      Effective intervention models were identified from an existing evidence review
      ("what works for women"). Based on this, we conducted a systematic review of
      published and grey literature on the costs and cost-effectiveness of each
      intervention identified. Where possible, we compared incremental costs and
      effects. RESULTS: Our effectiveness search identified 36 publications, reporting
      on the effectiveness of 22 HIV interventions with a gender focus. Of these, 11
      types of interventions had a corresponding/comparable costing or cost
      effectiveness study. The findings suggest that couple counselling for the
      prevention of vertical transmission; gender empowerment, community mobilization,
      and female condom promotion for female sex workers; expanded female condom
      distribution for the general population; and post-exposure HIV prophylaxis for
      rape survivors are cost-effective HIV interventions. Cash transfers for
      schoolgirls and school support for orphan girls may also be cost-effective in
      generalized epidemic settings. CONCLUSIONS: There has been limited research to
      assess the cost-effectiveness of interventions that seek to address women's needs
      and transform harmful gender norms. Our review identified several promising, cost
      effective interventions that merit consideration as critical enablers in HIV
      investment approaches, as well as highlight that broader gender and development
      interventions can have positive HIV impacts. By no means an exhaustive package,
      these represent a first set of interventions to be included in the investment
      framework.

PMID- 25373520
TI  - Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2
      specific chimeric antigen receptor.
AB  - Natural killer (NK) cells are an important effector cell type for adoptive cancer
      immunotherapy. Similar to T cells, NK cells can be modified to express chimeric
      antigen receptors (CARs) to enhance antitumor activity, but experience with CAR
      engineered NK cells and their clinical development is still limited. Here, we
      redirected continuously expanding and clinically usable established human NK-92
      cells to the tumor-associated ErbB2 (HER2) antigen. Following GMP-compliant
      procedures, we generated a stable clonal cell line expressing a humanized CAR
      based on ErbB2-specific antibody FRP5 harboring CD28 and CD3zeta signaling
      domains (CAR 5.28.z). These NK-92/5.28.z cells efficiently lysed ErbB2-expressing
      tumor cells in vitro and exhibited serial target cell killing. Specific
      recognition of tumor cells and antitumor activity were retained in vivo,
      resulting in selective enrichment of NK-92/5.28.z cells in orthotopic breast
      carcinoma xenografts, and reduction of pulmonary metastasis in a renal cell
      carcinoma model, respectively. gamma-irradiation as a potential safety measure
      for clinical application prevented NK cell replication, while antitumor activity
      was preserved. Our data demonstrate that it is feasible to engineer CAR
      expressing NK cells as a clonal, molecularly and functionally well-defined and
      continuously expandable cell therapeutic agent, and suggest NK-92/5.28.z cells as
      a promising candidate for use in adoptive cancer immunotherapy. 

PMID- 25373521
TI  - Mesenchymal stem cells correct inappropriate epithelial-mesenchyme relation in
      pulmonary fibrosis using stanniocalcin-1.
AB  - Current hypotheses suggest that aberrant wound healing has a critical role in the
      pathogenesis of idiopathic pulmonary fibrosis (IPF). In these hypotheses,
      continuous TGF-beta1 secretion by alveolar epithelial cells (AECs) in abnormal
      wound healing has a critical role in promoting fibroblast differentiation into
      myofibroblasts. Mesenchymal stem cells (MSCs) home to the injury site and reduce
      fibrosis by secreting multifunctional antifibrotic humoral factors in IPF. In
      this study, we show that MSCs can correct the inadequate-communication between
      epithelial and mesenchymal cells through STC1 (Stanniocalcin-1) secretion in a
      bleomycin-induced IPF model. Inhalation of recombinant STC1 shows the same
      effects as the injection of MSCs. Using STC1 plasmid, it was possible to enhance
      the ability of MSCs to ameliorate the fibrosis. MSCs secrete large amounts of
      STC1 in response to TGF-beta1 in comparison to AECs and fibroblasts. The
      antifibrotic effects of STC1 include reducing oxidative stress, endoplasmic
      reticulum (ER) stress, and TGF-beta1 production in AECs. The STC1 effects can be
      controlled by blocking uncoupling protein 2 (UCP2) and the secretion is affected
      by the PI3/AKT/mTORC1 inhibitors. Our findings suggest that STC1 tends to correct
      the inappropriate epithelial-mesenchymal relationships and that STC1 plasmid
      transfected to MSCs or STC1 inhalation could become promising treatments for IPF.

PMID- 25373523
TI  - Feasibility of SPECT myocardial perfusion imaging in the super-obese using a
      multi-head semiconductor camera with attenuation correction.
AB  - BACKGROUND: Obesity is not only associated with an increased risk of coronary
      artery disease, but also decreases the accuracy of many diagnostic modalities
      pertinent to this disease. Advances in myocardial perfusion imaging (MPI) have
      mitigated somewhat the effects of obesity, although the feasibility of MPI in the
      super-obese (defined as a BMI > 50) is currently untested. We undertook this
      study to assess the practicality of MPI in the super-obese using a multi-headed
      solid-state gamma camera with attenuation correction. METHODS: We retrospectively
      identified consecutive super-obese patients referred for MPI at our institution.
      The images were interpreted by 3 blinded, experienced readers and graded for
      quality and diagnosis, and subjectively evaluated the contribution of attenuation
      correction. Clinical follow-up was obtained from review of medical records.
      RESULTS: 72 consecutive super-obese patients were included. Their BMI ranged from
      50 to 67 (55.7 +/- 5.1). Stress image quality was considered good or excellent in
      45 (63%), satisfactory in 24 (33%), poor in 3 (4%), and uninterpretable in 0
      patients. Rest images were considered good or excellent in 34 (49%), satisfactory
      in 23 (33%), poor in 13 (19%), and uninterpretable in 0 patients. Attenuation
      correction changed the interpretation in 34 (47%) of studies. CONCLUSIONS: MPI is
      feasible and provides acceptable image quality for super-obese patients, although
      it may be camera and protocol dependent.

PMID- 25373522
TI  - Use of biologic agents in combination with other therapies for the treatment of
      psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disorder, which is associated with a
      significant negative impact on a patient's quality of life. Traditional therapies
      for psoriasis are often not able to meet desired treatment goals, and high-dose
      and/or long-term use is associated with toxicities that can result in end-organ
      damage. An improved understanding of the involvement of cytokines in the etiology
      of psoriasis has led to the development of biologic agents targeting tumor
      necrosis factor (TNF)-alpha and interleukins (ILs)-12/23. While biologic agents
      have improved treatment outcomes, they are not effective in all individuals with
      psoriasis. The combination of biologic agents with traditional therapies may
      provide improved therapeutic options for patients who inadequately respond to a
      single drug or when efficacy may be increased with supplementation of another
      treatment. In addition, combination therapy may reduce safety concerns and
      cumulative toxicity, as lower doses of individual agents may be efficacious when
      used together. This article reviews the current evidence available on the
      efficacy and safety of combining biologic agents with systemic therapies
      (methotrexate, cyclosporine, or retinoids) or with phototherapy, and the
      combination of biologic agents themselves. Guidance is provided to help
      physicians identify situations and the characteristics of patients who would
      benefit from combination therapy with a biologic agent. Finally, the potential
      clinical impact of biologic therapies in development (e.g., those targeting IL
      17A, IL-17RA, or IL-23 alone) is analyzed. 

PMID- 25373525
TI  - The onion ring sign.

PMID- 25373526
TI  - Andrew Benson honored on birthday No 97.
AB  - We present a brief account of the 97th birthday celebration of Andrew A. Benson,
      a scientific legend who is known, among other contributions, for his pioneering
      work on the path of carbon in photosynthesis (the Calvin-Benson cycle). 

PMID- 25373528
TI  - Low dietary intake of magnesium is associated with increased externalising
      behaviours in adolescents.
AB  - OBJECTIVE: Adequate Zn and Mg intakes may be beneficial for the prevention and
      treatment of mental health problems, such as depression, anxiety and attention
      deficit hyperactivity disorder. We aimed to investigate the prospective
      association between dietary intakes of Zn and Mg and internalising and
      externalising behaviour problems in a population-based cohort of adolescents.
      DESIGN: Prospective analysis (general linear mixed models) of dietary intakes of
      Zn and Mg assessed using a validated FFQ and mental health symptoms assessed
      using the Youth Self-Report (YSR), adjusting for sex, physical activity, family
      income, supplement status, dietary misreporting, BMI, family functioning and
      energy intake. SETTING: Western Australian Pregnancy Cohort (Raine) Study.
      SUBJECTS: Adolescents (n 684) at the 14- and 17-year follow-ups. RESULTS: Higher
      dietary intake of Mg (per SD increase) was significantly associated with reduced
      externalising behaviours (beta = -1.45; 95% CI -2.40, -0.50; P = 0.003). There
      was a trend towards reduced externalising behaviours with higher Zn intake (per
      SD increase; beta = -0.73; 95% CI -1.57, 0.10; P = 0.085). CONCLUSIONS: The study
      shows an association between higher dietary Mg intake and reduced externalising
      behaviour problems in adolescents. We observed a similar trend, although not
      statistically significant, for Zn intake. Randomised controlled trials are
      necessary to determine any benefit of micronutrient supplementation in the
      prevention and treatment of mental health problems in adolescents.

PMID- 25373527
TI  - "Doctor, what would you do?": physicians' responses to patient inquiries about
      periviable delivery.
AB  - OBJECTIVE: To qualitatively assess obstetricians' and neonatologists' responses
      to standardized patients (SPs) asking "What would you do?" during periviable
      counseling encounters. METHODS: An exploratory single-center simulation study.
      SPs, portraying a pregnant woman presenting with ruptured membranes at 23 weeks,
      were instructed to ask, "What would you do?" if presented options regarding
      delivery management or resuscitation. Responses were independently reviewed and
      classified. RESULTS: We identified five response patterns: 'Disclose' (9/28),
      'Don't Know' (11/28), 'Deflect' (23/28), 'Decline' (2/28), and 'Ignore' (2/28).
      Most physicians utilized more than one response pattern (22/28). Physicians
      'deflected' the question by: restating or offering additional medical
      information; answering with a question; evoking a hypothetical patient; or
      redirecting the SP to other sources of support. When compared with
      neonatologists, obstetricians (40% vs. 15%) made personal or professional
      disclosures more often. Though both specialties readily acknowledged the
      importance of values in making a decision, only one physician attempted to elicit
      the patient's values. CONCLUSION: "What would you do?" represented a missed
      opportunity for values elicitation. Interventions are needed to facilitate values
      elicitation and shared decision-making in periviable care. PRACTICE IMPLICATIONS:
      If physicians fail to address patients' values and goals, they lack the
      information needed to develop patient-centered plans of care.

PMID- 25373529
TI  - The impact of body mass on inflammatory markers and insulin resistance in
      polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate inflammatory markers and insulin resistance (IR) in women
      with and without polycystic ovary syndrome (PCOS), with different body mass index
      (BMI). METHODS: Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and
      C-reactive protein (CRP) were assessed in serum samples from 40 women in
      reproductive age. Patients were divided into four groups: I (non-eutrophic with
      PCOS, n = 12), II (non-eutrophic without PCOS, n = 10), III (eutrophic with PCOS,
      n = 8) and IV (eutrophic without PCOS, n = 10) being non-eutrophic, the
      overweight and obese women with BMI > 25 kg/m2 and eutrophic women with BMI <
      24.9 kg/m2. Homeostatic model assessment (HOMA-IR) was calculated for evaluation
      of IR. RESULTS: PCOS patients showed increased levels of CRP (p < 0.01) and HOMA
      IR (p < 0.01). When divided by BMI, both non-eutrophicad eutrophic PCOS showed
      increased CRP levels (p < 0.01) and HOMA-IR (p < 0.01). There were no differences
      in TNF-alpha and IL-6 levels between groups. CONCLUSION: In the PCOS group, the
      levels of CRP and IR were elevated, compared to their counterparts, regardless of
      body mass.

PMID- 25373530
TI  - Prior statin use and 90-day mortality in Gram-negative and Gram-positive
      bloodstream infection: a prospective observational study.
AB  - In several studies on patients with bloodstream infection (BSI), prior use of
      statins has been associated with improved survival. Gram-positive and Gram
      negative bacteria alert the innate immune system in different ways. We,
      therefore, studied whether the relation between prior statin use and 90-day total
      mortality differed between Gram-positive and Gram-negative BSI. We conducted a
      prospective observational cohort study of 1,408 adults with BSI admitted to
      Levanger Hospital between January 1, 2002, and December 31, 2011. Data on the use
      of statins and other medications at admission, comorbidities, functional status,
      treatment, and outcome were obtained from the patients' hospital records. The
      relation of statin use with 90-day mortality differed between Gram-negative and
      Gram-positive BSI (p-value for interaction 0.01). Among patients with Gram
      negative BSI, statin users had significantly lower 90-day total mortality [odds
      ratio (OR) 0.42, 95 % confidence interval (CI) 0.23-0.75, p = 0.003]. The
      association remained essentially unchanged after adjusting for the effect of sex,
      age, functional status before the infection, and underlying diseases that were
      considered confounders (adjusted OR 0.38, 95 % CI 0.20-0.72, p = 0.003). A
      similar analysis of patients with Gram-positive BSI showed no association of
      statin use with mortality (adjusted OR 1.22, 95 % CI 0.69-2.17, p = 0.49). The
      present study suggests that prior statin use is associated with a lower 90-day
      total mortality in Gram-negative BSI, but not in Gram-positive BSI. 

PMID- 25373532
TI  - Interleukin-8 promotes human ovarian cancer cell migration by epithelial
      mesenchymal transition induction in vitro.
AB  - PURPOSE: It has been well established that high serum levels of interleukin-8 (IL
      8) in ovarian cancer result in a poor clinical outcome. Thus, the aim of this
      study was investigating the role of IL-8 in ovarian cancer development. METHODS:
      Two human ovarian cancer cell lines (SKOV3 and OVCAR3) were cocultured with IL-8
      (100 ng/L) for 24 h, then cell migration was determined by transwell assay.
      Epithelial-mesenchymal transition (EMT)-associated proteins including E-cadherin
      and beta-catenin, and phosphorylation status of beta-catenin were investigated by
      Western blot analysis. RESULTS: After treatment with IL-8 (100 ng/L) for 24 h,
      transwell assay result showed that the number of migrated ovarian cells increased
      significantly. Western blot analysis revealed that protein levels of E-cadherin
      were decreased, while that of beta-catenin were elevated both in IL-8 pretreated
      SKOV3 and OVCAR3 cells. We further found that phosphorylation status of beta
      catenin were elevated either in cytoplasm or in nucleus of these two ovarian
      cancer cell lines after treatment with IL-8 for 24 h. CONCLUSIONS: Our data
      suggest that IL-8 induces EMT in ovarian cancer cells and implicates its
      potential role in enhancing ovarian cancer cell metastasis.

PMID- 25373531
TI  - Recommendations for radiological diagnosis and assessment of treatment response
      in lung cancer: a national consensus statement by the Spanish Society of Medical
      Radiology and the Spanish Society of Medical Oncology.
AB  - The last decade has seen substantial progress in the diagnostic and therapeutic
      approach to lung cancer, thus meaning that its prognosis has improved. The
      Spanish Society of Medical Radiology and the Spanish Society of Medical Oncology
      have therefore produced a national consensus statement to make recommendations
      for radiological diagnosis and assessment of treatment response in patients with
      lung cancer. This expert group recommends multi-detector computed tomography as
      the technique of choice for investigating this disease. The radiology report
      should include a full assessment by the TNM staging system. Lastly, when the
      patient is on immunotherapy, response evaluation should employ not only response
      evaluation criteria in solid tumours, but also immune-related response criteria. 

PMID- 25373533
TI  - Updated guidelines for biomarker testing in colorectal carcinoma: a national
      consensus of the Spanish Society of Pathology and the Spanish Society of Medical
      Oncology.
AB  - Publication of this consensus statement is a joint initiative of the Spanish
      Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM),
      intended to revise and update the diagnostic and treatment recommendations
      published 2 years ago on biomarker use and the management of patients with
      colorectal carcinoma (CRC), thereby providing an opportunity to improve
      healthcare efficiency and resource use in these patients. This expert group
      recommends testing for KRAS and NRAS status in all patients with metastatic CRC
      being considered for anti-epidermal growth factor receptor (anti-EGFR) therapy,
      as this type of treatment should only be used in patients not harbouring
      mutations in these genes. In contrast, testing for BRAF, EGFR, PI3K and PTEN
      mutation status is not necessary for therapeutic decision making, so does not
      need to be done routinely.

PMID- 25373534
TI  - Repetitive DNA chromosomal organization in the cricket Cycloptiloides americanus:
      a case of the unusual X1X 20 sex chromosome system in Orthoptera.
AB  - A common placement for most sex chromosomes that is involved in their
      evolutionary histories is the accumulation of distinct classes of repetitive
      DNAs. Here, with the aim of understanding the poorly studied repetitive DNA
      organization in crickets and its possible role in sex chromosome differentiation,
      we characterized the chromosomes of the cricket species Cycloptiloides
      americanus, a species with the remarkable presence of the unusual sex chromosome
      system X1X20?/X1X1X2X2?. For these proposes, we used C-banding and mapping
      through the fluorescence in situ hybridization of some repetitive DNAs. The C
      banding and distribution of highly and moderately repetitive DNAs (C 0t-1 DNA)
      varied depending of the chromosome. The greater accumulation of repetitive DNAs
      in the X2 chromosome was evidenced. The microsatellites were spread along entire
      chromosomes, but (AG)10 and (TAA)10 were less enriched, mainly in the centromeric
      areas. Among the multigene families, the 18S rDNA was spread throughout almost
      all of the chromosomes, except for pair 5 and X2, while the U2 snDNA was placed
      exclusively in the largest chromosome. Finally, the 5S rDNA was exclusively
      located in the short arms of the sex chromosomes. The obtained data reinforce the
      importance of chromosomal dissociation and inversion as a primary evolutionary
      mechanism to generate neo-sex chromosomes in the species studied, followed by the
      repetitive DNAs accumulation. Moreover the exclusive placement of 5S rDNA in the
      sex chromosomes suggests the involvement of this sequence in sex chromosome
      recognition throughout meiosis and, consequently, their maintenance, in addition
      to their avoiding degeneration. 

PMID- 25373535
TI  - Is complete liver resection without resection of synchronous lung metastases
      justified?
AB  - BACKGROUND: Advances in multidisciplinary care are changing the prognostic impact
      of colorectal lung metastases. Resection of colorectal liver metastases (CLM) may
      benefit patients with synchronous lung metastases even when lung metastases are
      not resected. The aim of this study was to investigate the survival of patients
      undergoing complete resection of CLM in the setting of unresected lung
      metastases. PATIENTS AND METHODS: We compared survival among 98 patients who
      underwent resection of CLM with unresected lung metastases, 64 who received only
      chemotherapy for limited colorectal liver and lung metastases, and 41 who
      underwent resection of both liver and lung metastases. Prognostic factors were
      investigated in the patients who underwent resection of CLM only. RESULTS: The 3
      year/5-year overall survival (OS) rates of patients with CLM resection only (42.9
      %/13.1 %) were better than those of patients treated with chemotherapy only (14.1
      %/1.6 %; p < 0.01) but worse than those of patients with resection of liver and
      lung metastases (68.9 %/56.9 %; p < 0.01). Multivariate analysis of patients with
      CLM resection only revealed that KRAS mutation [hazard ratio (HR) 2.10; 95 %
      confidence interval (CI) 1.21-3.64; p < 0.01] and rectal primary tumor (HR 1.72;
      95 % CI 1.02-2.88; p = 0.04) were independent predictors of worse OS. Survival of
      patients without these risk factors was similar to that of patients with curative
      metastasectomy. CONCLUSIONS: Complete resection of metastases remains the primary
      goal of treatment for stage IV colorectal cancer. Resection of CLM without
      resection of lung metastases is associated with an intermediate survival between
      that of patients treated with palliative and curative intent and should be
      considered in selected patients.

PMID- 25373536
TI  - Analysis of Recurrence Patterns After Anatomical or Non-anatomical Resection for
      Hepatocellular Carcinoma.
AB  - BACKGROUND: Recurrence patterns after hepatic resection has been poorly
      understood in view of tumor blood flow drainage (TBFD) area. Our goal was to
      clarify the recurrence patterns after anatomical versus nonanatomical hepatic
      resection for hepatocellular carcinoma (HCC). METHODS: A total of 424 consecutive
      patients with HCC, who were treated by curative resection (R0) at our hospital
      from 2001 to 2012, were evaluated. Among these, we compared the outcomes of the
      anatomical resection group (AR group, n = 243) and the nonanatomical resection
      group (NR group, n = 181). We performed an analysis of the recurrence patterns of
      HCC based on the preoperative CT during hepatic arteriography in these 424
      patients. RESULTS: Preoperative liver function was better in the AR group than
      the NR group (P < 0.001), and tumor size was larger in the AR group than the NR
      group (P < 0.001). HCC recurrence was recorded in 145 patients (59.7 %) of the AR
      group and 102 patients (56.4 %) of the NR group with no significant differences
      between the two groups (P = 0.590). The incidences of extrahepatic and
      intrahepatic recurrence (solitary/multiple) were similar between the two groups.
      In addition, the rate of recurrences by local dissemination, either recurrences
      in the same subsegment in the NR group or recurrences in the TBFD area in the AR
      group, was sufficiently low (1.4 %) as to be considered negligible. CONCLUSIONS:
      The incidence and patterns of HCC recurrence were similar between the anatomical
      and nonanatomical resection. Recurrence by local dissemination may be considered
      to be negligible in both surgical methods.

PMID- 25373537
TI  - Clinical Significance of Detecting Somatic Gene Mutations in Surgically Resected
      Adenosquamous Cell Carcinoma of the Lung in Japanese Patients.
AB  - BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR
      TKIs) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma
      kinase (EML4-ALK) inhibitors are effective and useful agents for treating
      patients who harbor EGFR-TKI-sensitive mutations or EML4-ALK rearrangement.
      Therefore, the importance of determining the presence of these somatic mutations
      when treating lung adenocarcinomas is widely accepted. However, genetic mutations
      are rarely evaluated in patients with adenosquamous cell carcinoma of the lung, a
      relatively infrequent histologic type of lung cancer, because of limited
      knowledge and the unclear value of assessing these oncogenic mutations in these
      patients. Therefore, we investigated the clinical implications of somatic
      mutations in surgically resected adenosquamous cell carcinoma of the lung in
      Japanese patients. METHODS: We retrospectively analyzed 32 patients with
      adenosquamous cell carcinoma of the lung who underwent surgical resection at two
      institutes in Japan. EGFR mutations and EML4-ALK rearrangement were assessed in
      all of the patients. RESULTS: Overall, 7 (21.9 %) of 32 patients had EGFR
      mutations: three patients had an exon 19 deletion and 4 had an exon 21, L858R
      mutation. There were no T790 M mutations. The median relapse-free survival was
      766 days and the median overall survival was 1,152 days in the total cohort.
      Relapse-free survival and overall survival were not significantly different
      between patients with or without EGFR mutations. CONCLUSIONS: Detecting EGFR
      mutations in patients with adenosquamous cell carcinoma is clinically important,
      especially in patients with disease recurrence because EGFR-TKIs may be effective
      in this histologic type of lung cancer.

PMID- 25373538
TI  - Re-place your BETs: the dynamics of super enhancers.

PMID- 25373539
TI  - Ubiquitin chain elongation: an intriguing strategy.

PMID- 25373540
TI  - Guide RNA functional modules direct Cas9 activity and orthogonality.
AB  - The RNA-guided Cas9 endonuclease specifically targets and cleaves DNA in a
      sequence-dependent manner and has been widely used for programmable genome
      editing. Cas9 activity is dependent on interactions with guide RNAs, and
      evolutionarily divergent Cas9 nucleases have been shown to work orthogonally.
      However, the molecular basis of selective Cas9:guide-RNA interactions is poorly
      understood. Here, we identify and characterize six conserved modules within
      native crRNA:tracrRNA duplexes and single guide RNAs (sgRNAs) that direct Cas9
      endonuclease activity. We show the bulge and nexus are necessary for DNA cleavage
      and demonstrate that the nexus and hairpins are instrumental in defining
      orthogonality between systems. In contrast, the crRNA:tracrRNA complementary
      region can be modified or partially removed. Collectively, our results establish
      guide RNA features that drive DNA targeting by Cas9 and open new design and
      engineering avenues for CRISPR technologies.

PMID- 25373541
TI  - Safety and feasibility of maximal physical testing in rheumatic diseases: a cross
      sectional study with 5,910 assessments.
AB  - The purpose of the study was to report on the safety and feasibility of the
      application of maximal physical tests in a heterogeneous cohort of rheumatic
      patients. This is a 5-year retrospective descriptive report on the incidence of
      events associated with maximal physical testing from 536 patients, totalizing
      5,910 tests. Tests were classified as cardiopulmonary, muscle strength, and
      physical functioning tests. Any adverse events during the tests and limiting
      factors incurring in tests cancellation were reported. Eighteen out of 641
      cardiopulmonary exercise tests had an adverse occurrence, with cardiac
      disturbance (1.4% of total tests) being the most prevalent. Moreover, 14 out of
      641 tests were not feasible. Out of 3,478 tests comprising leg press, bench
      press, knee extension, and handgrip tests, 15 tests had an adverse event. The
      most common occurrence was joint pain (0.4% of total tests), which was also the
      most frequent factor precluding testing (0.5% of total tests). Forty-five out of
      3,478 (1.3%) of the tests were not feasible. There was a very low incidence of
      events (0.2%) during the physical functioning tests. Joint pain was the only
      adverse event during the tests, whereas physical limitations were the most
      important barriers for the execution of the tests (1.1% of total tests). The
      incidence of limiting events in this test was 1.6% (n = 29). This report brings
      new data on the safety and feasibility of maximal physical testing in rheumatic
      patients. The physical tests described in this study may be applied for testing
      rheumatic patients both in research and clinical setting.

PMID- 25373543
TI  - Sequence variation of Epstein-Barr virus (EBV) BCRF1 in lymphomas in non-endemic
      areas of nasopharyngeal carcinoma.
AB  - To characterize the sequence variation and the potential implication of the
      Epstein-Barr virus (EBV) oncogene in lymphoma, BamHI-C fragment rightward reading
      frame 1 (BCRF1) was sequenced in different types of EBV-positive lymphoma in
      northern China, and polymorphisms were compared with previous variation data from
      other malignancies. The dominate subtype of BCRF1 in EBV-positive lymphoma was
      the B95-8 prototype, and a mutation in the signal peptide was more strongly
      associated with Hodgkin's lymphoma. The high conservation of BCRF1 in EBV
      positive lymphoma suggests its important role in maintaining the basic biological
      activity and immunosuppressive functions of the virus. 

PMID- 25373542
TI  - Associations of rs4810485 and rs1883832 polymorphisms of CD40 gene with
      susceptibility and clinical findings of Behcet's disease.
AB  - There are evidences that besides geographic tendency, interactions between
      genetic and environmental factors play an essential role in the pathogenesis of
      Behcet's disease (BD). In this study, we have evaluated the associations between
      rs4810485 and rs1883832 single nucleotide polymorphism (SNP)s of CD40 gene with
      the susceptibility and clinical findings of BD. Two hundred and eighty-five
      patients with BD and 225 age-matched healthy controls were enrolled in this
      study. The clinical findings of patients were noted. The distributions of
      genotypes, alleles, combined genotypes and haplotypes of these two SNPs in BD
      patients were compared with those in healthy controls. In further evaluation, we
      evaluated the patients with and without any of clinical findings with regarding
      to distribution of genotypes and alleles of these two SNPs. There was no
      significant difference concerning frequencies of genotypes, alleles, combined
      genotypes and haplotypes of rs4810485 and rs1883832 between patients and controls
      (p > 0.05 for all). Frequency of GT genotype of CD40 rs4810485 polymorphism was
      found to be significantly higher in patients with skin lesions (p < 0.05, OR
      1.65, 95 % CI 1.02-2.64). Also, we have found significantly higher frequencies of
      CC genotype and C allele of CD40 rs1883832 polymorphism in patients with genital
      ulcers (p < 0.05 for both, OR 2.30, 95 % CI 1.07-4.94 and OR 1.78, 95 % CI 1.06
      2.97, respectively). However, these significances were disappeared after
      Bonferroni correction. We suggest that differences in the expression levels of
      CD40 because of different genotypes of these two SNPs may take part in the
      development of skin lesions or genital ulcers in patients with BD.

PMID- 25373544
TI  - Bioaccumulation of BDE-47 and effects on molecular biomarkers
      acetylcholinesterase, glutathione-S-transferase and glutathione peroxidase in
      Mytilus galloprovincialis mussels.
AB  - Mussels, Mytilus galloprovincialis, showed a high bioaccumulation ability when
      exposed to waterborne tetrabromodiphenyl ether (BDE-47), with a bioconcentration
      factor of 10,900 L Kg(-1) wet weight, and slow depuration rates in clean
      seawater. Kinetic and concentration-response experiments were performed measuring
      in the exposed mussel the activities of three molecular biomarkers: glutathione S
      transferase (GST), glutathione peroxidase (GPx) and acetylcholinesterase (AChE).
      The long term (30 days) exposure of mussels to all concentrations (2-15 ug L(-1))
      of BDE-47 significantly inhibited the AChE and GST activities, a result that
      supports the suitability of these biomarkers in marine pollution monitoring
      programs. However, GPx activity showed a less consistent pattern of response
      depending on the concentration and the duration of exposure. 

PMID- 25373547
TI  - Global population: History, geopolitics, and life on earth.

PMID- 25373545
TI  - EPR detection of hydroxyl radical generation and oxidative perturbations in lead
      exposed earthworms (Eisenia fetida) in the presence of decabromodiphenyl ether.
AB  - Lead (Pb) and decabromodiphenyl ether (BDE209) are the main contaminants at e
      waste recycling sites, and their potential toxicological effects on terrestrial
      organisms have received extensive attention. However, the impacts on the
      oxidative perturbations and hydroxyl radical (.OH) generation in earthworms of
      exposure to the two chemicals remain almost unknown. Therefore, indoor incubation
      tests were performed on control and contaminated soil samples to determine the
      effects of Pb in earthworms Eisenia fetida in the presence of BDE209 through the
      use of several biomarkers in microcosms. The results have demonstrated that the
      addition of BDE209 (1 or 10 mg kg(-1)) decreased the enzymatic activities
      [superoxide dismutase, catalase (CAT), peroxidase] and total antioxidant capacity
      (T-AOC) compared with exposure to BDE209 alone (50, 250 or 500 mg kg(-1)).
      Electron paramagnetic resonance spectra indicated that .OH radicals in earthworms
      were significantly induced by Pb in the presence of BDE209. The changing pattern
      of malondialdehyde (MDA) contents was accordant with that of .OH intensity
      suggested that reactive oxygen species might lead to cellular lipid peroxidation.
      Furthermore, CAT exhibited more sensitive response to single Pb exposure than the
      other biomarkers, while T-AOC, .OH and MDA might be three most sensitive
      biomarkers in earthworms after simultaneous exposure to Pb and BDE209. The
      results of these observations suggested that oxidative stress appeared in E.
      fetida, and it may play an important role in inducing the Pb and BDE209 toxicity
      to earthworms. 

PMID- 25373548
TI  - [Implementation and use of biosimilars in the therapy of inflammatory rheumatic
      diseases: Statement of the German Society of Rheumatology].

PMID- 25373546
TI  - Ultrasonographic findings of Kimura's disease presenting in the upper
      extremities.
AB  - OBJECTIVE: To describe ultrasound findings of Kimura's disease arising in the
      upper extremities. MATERIALS AND METHODS: Five patients with Kimura's disease
      confirmed by surgical resection were retrospectively reviewed by two
      musculoskeletal radiologists and a pathologist. RESULTS: All six lesions involved
      the epitrochlear area and appeared as partially (n = 5) or poorly (n = 1)
      marginated subcutaneous masses with the presence of curvilinear hyperechoic bands
      intermingled within the hypoechoic components by US. Moderate (n = 4) to severe
      (n = 2) vascular signals were observed in some proportion of the hyperechoic
      bands by color Doppler US. The associated findings were the increased
      echogenicity of surrounding subcutaneous fat (n = 6) and adjacent lymphadenopathy
      (n = 4). Microscopic examination showed proliferation of lymphoid follicles with
      prominent germinal centers and intervening fibrosis. CONCLUSIONS: In this study,
      Kimura's disease arising in the upper extremities showed a partially defined
      hypoechoic subcutaneous mass with internal hyperechoic bands and moderate-to
      severe vascularities, increased echogenicity of the surrounding subcutaneous fat
      and adjacent lymphadenopathy on US. Thus, when these US features are observed in
      the typical epitrochlear region of an Asian individual, especially if accompanied
      by peripheral eosinophilia, Kimura's disease should be considered as a possible
      diagnosis.

PMID- 25373549
TI  - [Arthrodesis for patients with rheumatic arthritis of the ankle and hindfoot. A
      reasonable option?].
AB  - BACKGROUND: Ankle and hindfoot deformities as well as degenerative changes are
      often found in patients with rheumatological diseases. They often suffer from
      severe pain and complain of increasing immobility. Corrective procedures with
      ankle or hindfoot arthrodesis are promising options. OBJECTIVES: This article
      presents epidemiological data and describes the clinical aspects, diagnostics and
      treatment options for patients with ankle and hindfoot osteoarthritis. MATERIALS
      AND METHODS: The retrospective results of 56 patients after ankle or hindfoot
      arthrodesis are presented. RESULTS: After an average follow-up of 52 months the
      majority of results were good or excellent with relief of pain and reconstruction
      of the function of the foot. CONCLUSION: Ankle or hindfoot arthrodesis represents
      a promising option for patients with severe osteoarthritis and can safeguard
      patients from increasing immobility.

PMID- 25373550
TI  - [Rheumatic tendon pathologies].
AB  - BACKGROUND: Rheumatoid arthritis is found in approximately 2 % of the total
      population in Europe and the peak incidence of the disease is during the fourth
      and fifth decades of life. In approximately 15 % the first symptoms of the
      disease occur at the level of the foot and ankle. If the early stage-dependent
      therapy with pharmaceuticals fails isolated surgery of the tendons (e.g.
      tenosynovectomy) and reconstructive surgery including the tendons (e.g. tendon
      transfer and tendon readaptation) are performed to keep the patient mobile.
      OBJECTIVES: The aim of this article is to give an overview of the most commonly
      used interventions in the reconstruction of tendons in rheumatism patients and
      the corresponding indications. The conservative therapy options for rheumatic
      foot and ankle alterations with a special emphasis on tendon pathologies have a
      well-established importance and are also presented. METHODS: A selective
      literature search was carried out for therapeutic options of rheumatic tendon
      pathologies. DISCUSSION: If possible attempts should be made to preserve
      functional qualities using tenosynovectomy, tendon sutures or tendon transfer
      operations. If joints are already destroyed or dislocated, tendon operations
      should be carried out only as combined interventions with arthrodesis,
      endoprostheses or resection arthroplasty. The time window in which these
      interventions are possible should not be missed. Orthotic devices, bandages or
      even orthopedic shoes provide external support and splinting but do not represent
      a causal therapy.

PMID- 25373551
TI  - Different structures of heterogeneous starch granules from high-amylose rice.
AB  - High-amylose cereal starches usually have heterogeneous starch granules in
      morphological structure. In the present study, the polygonal, aggregate,
      elongated, and hollow starch granules were separated from different regions of
      the kernels of high-amylose rice, and their structures were investigated. The
      results showed that the polygonal starch granules had low amylose content and
      high short branch-chain and branching degree of amylopectin, and exhibited A-type
      crystallinity. The aggregate starch granules had high long branch-chain of
      amylopectin, relative crystallinity, and double helix content, and exhibited C
      type crystallinity. The elongated starch granules had high amylose content and
      low branching degree of amylopectin and relative crystallinity, and exhibited C
      type crystallinity. The hollow starch granules had very high amylose content,
      proportion of amorphous conformation, and amylose-lipid complex, and very low
      branch-chain of amylopectin, branching degree of amylopectin, and double helix
      content, and exhibited no crystallinity. The different structures of
      heterogeneous starch granules from high-amylose rice resulted in significantly
      different thermal properties. 

PMID- 25373552
TI  - Laparoscopic versus open distal pancreatectomy: a single-institution comparative
      study.
AB  - BACKGROUND: This study was designed to compare clinical outcomes for laparoscopic
      distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) performed at a
      single institution. METHODS: This retrospective study included 43 patients who
      underwent distal pancreatectomy between 2009 and 2013. The patients were divided
      into two groups based on the surgical approach: the laparoscopic surgery group
      (n=20) and the open surgery group (n=23). All clinical data were analyzed
      retrospectively. RESULTS: There were no significant differences in operation
      time, rate of intraoperative transfusions, complications, or mortality between
      the two groups. The intraoperative blood loss (210+/-84.4 mL vs. 420+/-91.1 mL),
      first flatus time (1.5+/-1 d vs. 4+/-2.5 d), diet start time (2+/-0.7 d vs. 6+/
      1.8 d), and postoperative hospital stay (8+/-3.5 d vs. 14+/-5.5 d) were
      significantly less in the LDP group than in the ODP group. All patients had
      negative surgical margins at final pathology. There were no significant
      differences in the number of lymph nodes harvested (10+/-2.1 vs. 11+/-3.2)
      between the two groups. CONCLUSIONS: LDP is a feasible and safe surgical approach
      as well as ODP, but has the advantages of an earlier return to normal bowel
      movements, normal diet, and shorter hospital stays than ODP.

PMID- 25373553
TI  - [Focus Notified Bodies. New requirements for designation and monitoring].
AB  - For medical devices with a higher risk, Notified Bodies assess whether the
      manufacturers and their products fulfill the requirements laid down in the
      European directives on medical devices. Notified Bodies are designated through a
      designation procedure by the designating authority, in Germany by ZLG. The
      requirements for the designation arise from the respective annexes of the
      directives on medical devices. Since these are only minimal criteria, different
      documents have been compiled on a European and national level to concretize these
      minimal criteria regarding the organization, quality management system,
      resources, and certification procedure. The rules of the ZLG are thereby the
      essential documents for designation in Germany. Moreover, according to
      Implementing Regulation (EU) no. 912/2013, the European commission and the other
      European designating authorities also have to be involved in the designation
      process. The aim of continuous monitoring of the Notified Bodies with assessments
      on the bodies' premises as well as with observed audits is to ensure the
      permanent fulfillment of the requirements. If nonconformities are found in a
      body's quality management system or in its implementation of the conformity
      assessment procedures, the body is obliged to provide ZLG with a corrective
      actions plan. In the case that the nonconformities are not resolved in time or
      critical nonconformities are found, ZLG may take actions, e.g., restrict the
      scope of designation, suspend, or - as last resort - withdraw the designation. 

PMID- 25373554
TI  - Baicalein induces apoptosis of human cervical cancer HeLa cells in vitro.
AB  - A number of studies have shown that baicalein shows high antitumor activity in
      vitro and in vivo. In this study, the inhibitory effect of baicalein on human
      cervical cancer HeLa cells was studied in vitro. HeLa cells were treated with
      high (100 ug/ml) and low (50 ug/ml) doses of baicalein, and cell growth
      inhibition rates were examined by the MTT assay. The morphological changes of
      apoptotic cells were observed under the light and electron microscope, while the
      rate of cell apoptosis was examined by flow cytometry. The expression of
      apoptosis-related proteins was analyzed by western blot, and caspase-3 activation
      was examined by a caspase-3 activity assay and spectrophotometry. The results
      demonstrated that baicalein inhibits the proliferation of HeLa cells and induces
      apoptosis in a caspase-3-dependent pathway, through downregulation of the B-cell
      lymphoma 2 (Bcl-2) protein and upregulation of the Bcl-2-associated X protein
      (Bax), Fas, Fas ligand (FasL) and caspase-8. Thus, we conclude that baicalein
      induces apoptosis of HeLa cells via the mitochondrial and the death receptor
      pathways. Cell apoptosis in HeLa cells was most likely promoted by the activation
      of the proteolytic enzyme caspase-3 in both pathways.

PMID- 25373555
TI  - Polysemy Advantage with Abstract But Not Concrete Words.
AB  - It is a robust finding that ambiguous words are recognized faster than
      unambiguous words. More recent studies (e.g., Rodd et al. in J Mem Lang 46:245
      266, 2002) now indicate that this ambiguity advantage may in reality be a
      polysemy advantage: caused by related senses (polysemy) rather than unrelated
      meanings (homonymy). We report two lexical decision studies that investigated the
      effects of polysemy with new word sets. In both studies, polysemy was factorially
      manipulated while homonymy was controlled for. In Experiment 1, where the
      stimulus set consisted solely of concrete nouns, there was no effect of polysemy.
      However, in Experiment 2, where the stimulus set consisted of a mix of abstract
      nouns, verbs, and adjectives, there was a significant polysemy advantage.
      Together, these two studies strongly suggest that polysemy affects abstract but
      not concrete nouns. In addition, they rule out several alternative explanations
      for these polysemy effects, e.g., sense dominance, age-of-acquisition,
      familiarity, and semantic diversity. 

PMID- 25373556
TI  - Self-assembled monolayers of alkanethiolates on surface chemistry groups in
      osteosarcoma cells.
AB  - Cell biomedical behavior is influenced by a number of factors, and the
      extracellular matrix (ECM) of the cellular microenvironment affects certain
      cancer cells. In the current study, U-2OS cells were cultured on gold surfaces
      modified with different terminal chemical groups [methyl (-CH3), amino (-NH2),
      hydroxyl (-OH) and carboxyl (-COOH)]. The results revealed that different
      chemical surfaces convey different behaviors. The density of the different
      functional surfaces was confirmed by atomic force microscopy. Cell morphology,
      proliferation rate and cell cycle were investigated using scanning electron
      microscopy, cell counting and flow cytometry. In conclusion, the type of chemical
      group on a biomaterial is an important property for the growth of osteosarcoma
      cells; -NH2 and -COOH surfaces sustained visible cell adhesion and promoted cell
      growth. 

PMID- 25373557
TI  - Overexpression of the chimeric plasmin-resistant VEGF165/VEGF183 (132-158)
      protein in murine breast cancer induces distinct vascular patterning adjacent to
      tumors and retarded tumor growth.
AB  - A chimeric plasmin-resistant vascular endothelial growth factor (VEGF)165/VEGF183
      (132-158) protein, named as VEGF183 (according to the nomenclature of VEGF),
      designed by a previous study, was demonstrated to have an enhanced affinity for
      the extracellular matrix (ECM) amongst other bioactivities. However, it is now
      accepted that mutant VEGFs frequently demonstrate different angiogenic activities
      and produce different vascular patterning from the parental molecule. The present
      study hypothesized that VEGF183, due to its enhanced binding affinity to the ECM,
      would exhibit a different angiogenic activity and produce a different vascular
      patterning compared to those of VEGF165. Murine breast cancer EMT-6 cells were
      manipulated to stably overexpress VEGF165 or VEGF183. These cells were then
      inoculated intradermally into BALB/c mice in order to monitor the formation of
      vascular patterning in skin proximal to tumors. In vivo angiogenesis experiments
      revealed that overexpression of VEGF183 in murine breast cancer cells resulted in
      irregular, disorganized and dense vascular patterning as well as induced a
      significant inhibition of tumor growth compared with that of VEGF165. In
      addition, allograft tumor immunochemical assays of VEGF183-overexpressing tumors
      demonstrated significantly lower vascular densities than those of VEGF165
      overexpressing tumors; however, VEGF183 tumors had a significantly enlarged
      vascular caliber. Conversely, cell wound healing experiments revealed that
      VEGF183-overexpressing EMT-6 cells had significantly decreased migration rates
      compared with those of VEGF165-overexpressing EMT-6 cells. In conclusion, the
      results of the present study supported the hypothesis that the altered ECM
      affinity of VEGF induced structural alterations to vasculature. In addition,
      these results provided a novel insight into VEGF design and indirect evidence for
      the function of exon 8 in VEGF. [Corrected]

PMID- 25373558
TI  - Associations of physical activity with sleep satisfaction, perceived stress, and
      problematic Internet use in Korean adolescents.
AB  - BACKGROUND: The association of physical activity (PA) with sleep quality,
      perceived stress, and problematic Internet use was examined in a nationwide
      sample of Korean adolescents. METHODS: Data from the 2010 Korean Youth Risk
      Behavior Web-based Survey collected from 73,238 Korean adolescents aged 12-18
      years (mean age 15.06 +/- 1.75 years) were analyzed. Participants were asked to
      rate the frequency with which they engaged in moderate and vigorous PA per week.
      The risk of problematic Internet use was assessed with the Korean Internet
      Addiction Proneness Scale for Youth-Short Form. Self-report questionnaires were
      used to assess levels of sleep satisfaction and perceived stress. The
      associations of PA with sleep satisfaction, perceived stress, and problematic
      Internet use were assessed with multiple logistic regression analysis. Then, the
      Sobel test was used to explore the mediation of the relationship between PA and
      problematic Internet use by sleep satisfaction and stress. RESULTS: Physically
      active subjects were more likely to express satisfaction with their sleep (AOR =
      1.13; 95% CI = 1.08, 1.18), less likely to feel stress in their lives (AOR =
      0.89, 95% CI = 0.86, 0.93), and less likely to be a problematic Internet user
      (AOR = 0.78; 95% CI = 0.73, 0.82) compared to physically inactive subjects. The
      Sobel test revealed that the inverse association between PA and problematic
      Internet use was partially mediated by increased sleep satisfaction or decreased
      perceived stress (Z = -4.315, p = 0.001). CONCLUSIONS: The results of the present
      study indicate a negative association between level of physical activity and risk
      of problematic Internet use via the mediation of sleep satisfaction and stress in
      Korean adolescents. Physical activity may be helpful to improve adolescent mental
      health.

PMID- 25373559
TI  - The study on hemodynamic effect of varied support models of BJUT-II VAD on
      coronary artery: a primary CFD study.
AB  - BJUT-II VAD (Beijing University of Technology ventricular assist device II) is a
      novel left ventricular assist device. Because of the special connection between
      the pump and native heart, the hemodynamic effects of BJUT-II VAD on coronary
      artery are still unclear. Hence, numerical simulations have been conducted to
      clarify changes in hemodynamic effects of different support modes. A patient
      specific left coronary arterial geometric model is reconstructed based on the
      computed tomography (CT) data. Three support modes, "constant speed mode," "co
      pulse mode," and "counter pulse mode," are used in this study. The wall shear
      stress (WSS), wall shear stress gradient (WSSG), cycle-averaged wall shear stress
      (avWSS), oscillatory shear index (OSI), and the flow pattern are calculated to
      evaluate the hemodynamic states of coronary artery. The computational results
      demonstrate that the hemodynamic states of coronary artery are directly affected
      by the support modes. The co-pulse modes could achieve the highest blood
      perfusion (constant speed: 153 ml/min vs. co-pulse: 775 ml/min vs. counter pulse:
      140 ml/min) and the highest avWSS (constant speed: 18.1 Pa vs. co-pulse: 42.6 Pa
      vs. counter pulse: 22.6 Pa). In addition, both the WSS and WSSG at the time of
      peak blood velocity under the constant speed mode are lower than those under
      other two support modes. In contrast, the counter pulse mode generates the
      highest OSI value (constant speed: 0.365 vs. co-pulse: 0.379 vs. counter pulse:
      0.426). BJUT-II VAD under co-pulse mode may have benefits for improving coronary
      perfusion and preventing the development of atherosclerosis; however, the
      constant speed mode may have benefit for preventing the development of plaque
      vulnerability. 

PMID- 25373560
TI  - The Behavioral Physiology and Antidepressant Mechanisms of Electroconvulsive
      Shock.
AB  - OBJECTIVE: This study aimed to determine whether the association between
      antidepressant (AD) and anticonvulsant effects of electroconvulsive therapy
      constitutes a necessary, causal relationship. METHODS: The rats received corneal
      kindling to induce an epileptic focus, whereas electroconvulsive shock (ECS) was
      given antagonistically. The forced swim test (FST; a model of AD efficacy),
      cumulative kindling scores (indexing epileptogenesis), and clonus duration
      (measuring anticonvulsant effects) were used to assess the effects of ECS.
      Intensity and route of administration (corneal vs pinnate) of ECS were varied
      within or across 2 experiments. RESULTS: Under various conditions, an increase in
      mobility in the FST (an index of AD properties) was observed in the absence of
      any retardation of kindling; under other conditions, an antiepileptogenic effect
      occurred in the absence of any change in immobility in the FST. In addition, 2
      forms of ECS treatment had equal AD properties, whereas only 1 of the 2
      treatments reduced clonus time (suggesting an elevated seizure threshold).
      CONCLUSIONS: In a rat model, putative AD effects of ECS are dissociable from its
      antiepileptogenic and anticonvulsant effects, suggesting different stimulus
      thresholds for the various effects of corneal ECS: the antiepileptogenic effect
      required a lower current dose than the behavioral effect in the FST, whereas the
      anticonvulsant effect required the highest stimulation level. With transpinnate
      ECS, the threshold for the behavioral effect in the FST and the antiepileptogenic
      threshold were reversed.

PMID- 25373561
TI  - Acute electroconvulsive therapy followed by maintenance electroconvulsive therapy
      decreases hospital re-admission rates of older patients with severe mental
      illness.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is a highly effective treatment for
      patients with severe mental illness (SMI). Maintenance ECT (M-ECT) is required
      for many elderly patients experiencing severe recurrent forms of mood disorders,
      whereas M-ECT for schizophrenia patients is a poorly studied treatment. We report
      on the outcomes in aged patients with SMI: schizophrenia and severe affective
      disorders treated by M-ECT of varying duration to prevent relapse after a
      successful course of acute ECT. The study measured the effectiveness of M-ECT in
      preventing hospital readmissions and reducing admission days. METHOD: A
      retrospective chart review of 42 consecutive patients comparing the number and
      length of psychiatric admissions before and after the start of M-ECT was used. We
      analyzed diagnoses, previous ECT treatments, number of ECT treatments, and number
      and length of psychiatric admissions before and after M-ECT. RESULTS: Mean age in
      our sample was 71.5 (6.9) years. Twenty-two (52%) patients experienced severe
      affective disorders and 20 (48%) experienced schizophrenia. Patients were
      administered 92.8 (85.9) M-ECT treatments. Average duration of the M-ECT course
      was 34 (29.8) months. There were on average 1.88 admissions before M-ECT and only
      0.38 admissions in the M-ECT period (P < 0.001). Duration of mean hospitalization
      stay decreased from 215.9 to 12.4 days during the M-ECT (P < 0.01). CONCLUSIONS:
      Our findings suggest that acute ECT followed by M-ECT is highly effective in
      selected elderly patients with SMIs.

PMID- 25373562
TI  - Electroconvulsive Therapy Malpractice: Verdict for the Defense.
AB  - OBJECTIVES: Malpractice cases involving electroconvulsive therapy (ECT) are rare.
      Even rarer are those malpractice cases alleging ECT-related brain damage. The few
      cases of ECT malpractice lawsuits are not described in the medical literature in
      detail. METHODS: We provide a detailed account of a case of a patient and
      subsequent alleged ECT-related malpractice. The details of the case were collated
      using the handwritten notes of one of the authors who was present at the trial
      and the pretrial documents of discovery that were entered into evidence. RESULTS:
      The plaintiff alleged complete autobiographical amnesia after ECT, supposedly as
      a result of ECT-related brain damage. The defense was aided by the presence of
      extensive neurological examination and brain imaging both before and after ECT.
      The defense team also offered to the jury the concept of "dissociative amnesia"
      as an alternative explanation for the plaintiff's memory complaints. The case
      went to trial and was successfully defended. DISCUSSION: Electroconvulsive
      therapy malpractice cases alleging brain damage can be successfully defended, and
      the successful defense is aided by adequate documentation before, during, and
      after ECT. CONCLUSIONS: Malpractice cases, especially if they are baseless, can
      occur unpredictably, but they can be defended if the medical documentation is
      thorough.

PMID- 25373563
TI  - A new approach to determination of hydration equilibria constants for the case of
      [Er(EDTA)(H2O)(n)](-) complexes.
AB  - Two anionic complexes [Er(EDTA)(H2O)2](-) and [Er(EDTA)(H2O)3](-) were obtained
      in the form of the following compounds: [C(NH2)3]2[Er(EDTA)(H2O)2]ClO4.6H2O ()
      and Na[Er(EDTA)(H2O)3].5H2O (), respectively. The UV-vis-NIR absorption spectra
      of both monocrystals were measured at room temperature and at 4.2 K. The
      influence of the coordination number changes on intensities of the f-f
      transitions and the crystal field splitting of (2S+1)LJ multiplets are discussed.
      The weighted sum of molar absorption coefficients of f-f transitions in the
      spectra of and was used to reproduce the absorption bands of the Er(3+)-EDTA
      complex in aqueous solution. This approach allowed us to estimate that the
      complex in solution exists in 95% as the 8-coordinate [Er(EDTA)(H2O)2](-) species
      and in 5% as the 9-coordinate [Er(EDTA)(H2O)3](-) ones as well as to calculate
      the conditional hydration equilibrium constant (Kaqua) of the reaction:
      [Er(EDTA)(H2O)3](-) <-> [Er(EDTA)(H2O)2](-) + H2O which is rather difficult to
      determine by using other methods. The Kaqua value was found to be 19 +/- 1. 

PMID- 25373564
TI  - Wear performance of bovine tooth enamel against translucent tetragonal zirconia
      polycrystals after different surface treatments.
AB  - The wear performances of bovine tooth enamel (BTE) against translucent tetragonal
      zirconia polycrystals (TZP) compared to that of feldspar porcelain and the
      influence of surface treatments of translucent TZP were investigated by the two
      body wear test. Translucent TZP and feldspar porcelain were used as hemisphere
      abrader specimens with a radius of curvature of 5 mm; flat BTE surfaces were used
      as substrate specimens. The cross-sectional area of the worn surfaces of the
      substrates and the wear volume of the antagonist abraders were measured. Surface
      roughness, hardness and coefficient of friction as well as SEM observations and
      EPMA analyses were also performed to investigate the underlying mechanism of
      wear. The results suggested that BTE is less susceptible to wear when translucent
      TZP is used as the antagonist in contrast to the use of feldspar porcelain, and
      that surface treatment of the TZP abraders significantly influenced the wear of
      BTE substrates. 

PMID- 25373565
TI  - Evaluating motivational interviewing to promote breastfeeding by rural Mexican
      American mothers: the challenge of attrition.
AB  - Although most Hispanic/Latino-American mothers initiate breastfeeding, duration
      and exclusivity of breastfeeding remain low. We explored whether a motivational
      interviewing (MI) intervention could help rural Mexican-American mothers continue
      breastfeeding. We used a two-group (MI intervention n = 26, attention control
      [AC] n = 27) repeated measures experimental design. Assessments and interventions
      occurred at 3 days, 2 weeks, and 6 weeks postpartum (time points when mothers are
      particularly vulnerable to discontinuing breastfeeding), with a final phone
      assessment at 6 months postpartum. We collected demographic data and measured
      intent to breastfeed for 6 months (intent question), self-efficacy (Breastfeeding
      Self-Efficacy Scale-Short Form), and collected breastfeeding information
      (breastfeeding assessment questionnaire). Independent t-tests and Mann Whitney U
      non-parametric tests were used to evaluate group differences (alpha = 0.05). High
      levels of attrition by week 6 impaired our ability to evaluate the potential of
      our MI intervention. No significant differences were found between groups for any
      of the outcome variables (intent to breastfeed for 6 months, breastfeeding self
      efficacy, and duration of breastfeeding). Though the mothers intended to
      breastfeed for 6 months and were confident in their ability to do so, most did
      not breastfeed for 6 months. At 6 months, mothers receiving the MI intervention
      had breastfed an average of 90 days compared to 82 days for those receiving the
      AC sessions and 22% of the mothers in each group were still breastfeeding at some
      level. Because of the impact of attrition during this study, we discuss factors
      that contributed to attrition and approaches to lessen this problem in future
      studies. Such efforts may require a greater investment of time and resources and
      should be budgeted accordingly. Culturally appropriate interventions are needed
      to help rural Mexican-American mothers meet their breastfeeding goals, thus
      providing an opportunity to reduce their children's risk of multiple diseases and
      obesity. Only when we address these considerations will we have an opportunity to
      decrease health disparities, promote healthy behaviors, and be trusted health
      care partners. 

PMID- 25373566
TI  - Chest pain and anxiety in an adolescent: an unusual etiology.
AB  - Chest pain in children is commonly caused by benign etiologies but may be caused
      by conditions that carry significant morbidity if not treated. Emergency medicine
      physicians must identify the patients that require further evaluation and
      treatment. We describe a case of a 13-year-old boy with 10 months of progressive
      chest pain that had been attributed to anxiety and was ultimately diagnosed as an
      esophageal duplication cyst requiring surgical repair. 

PMID- 25373567
TI  - Hemodialysis for near-fatal sodium phosphate toxicity in a child receiving sodium
      phosphate enemas.
AB  - OBJECTIVE: This study aimed to demonstrate the importance of considering
      hemodialysis as a treatment option in the management of sodium phosphate
      toxicity. METHODS: This is a case report of a 4-year-old who presented to the
      emergency department with shock, decreased mental status, seizures, and tetany
      due to sodium phosphate toxicity from sodium phosphate enemas. RESULTS:
      Traditional management of hyperphosphatemia with aggressive hydration and
      diuretics was insufficient to reverse the hemodynamic and neurological
      abnormalities in this child. This is the first report of the use of hemodialysis
      in a child without preexisting renal failure for the successful management of
      near-fatal sodium phosphate toxicity. CONCLUSIONS: Hemodialysis can safely be
      used as an adjunctive therapy in sodium phosphate toxicity to rapidly reduce
      serum phosphate levels and increase serum calcium levels in children not
      responding to conventional management.

PMID- 25373568
TI  - Extra-adrenal paraganglioma presenting as acute chest pain mimicking acute
      myocardial infarction in a 10-year-old boy.
AB  - Extraadrenal paragangliomas are rare pediatric tumors with variable symptoms that
      cause difficultly in diagnosis and delayed treatment. We report the case of a 10
      year-old boy who presented to the pediatric emergency department with acute chest
      pain and dyspnea mimicking a non-ST-segment elevation acute myocardial
      infarction. He was subsequently found to have an extraadrenal paraganglioma after
      a series of imaging and laboratory examinations. The mass was subsequently
      removed, and the diagnosis of extraadrenal paraganglioma was confirmed
      histologically. Acute coronary syndrome as the presenting feature of extraadrenal
      paragangliomas in pediatric population is an even rarer clinical entity. 

PMID- 25373569
TI  - Rapid response to treatment of heart failure resulting from hypocalcemic
      cardiomyopathy.
AB  - Hypocalcemia is a rare condition that causes dilated cardiomyopathy and can
      result in heart failure. Patients with hypocalcemia have been reported to recover
      in 3 to 12 months after calcium and vitamin D replacement therapy as well as
      treatment of heart failure. A 6-month-old male patient who presented with dyspnea
      was admitted to the intensive care unit with severe heart failure and dilated
      cardiomyopathy. Blood biochemistry revealed hypocalcemia and vitamin D
      deficiency. After administration of anticongestive treatment, positive inotropic
      support, as well as vitamin D and calcium supplementation, cardiac function
      returned to normal in a week. Our case is the first report of such a rapid
      improvement in cardiac morphology and function in a patient with hypocalcemic
      dilated cardiomyopathy and heart failure. 

PMID- 25373570
TI  - The case of the missing testicle: blunt scrotal trauma in the pediatric emergency
      department.
AB  - Serious blunt scrotal trauma in the pediatric population is rare and can pose
      significant danger to the viability of the testes. The following case describes
      an adolescent boy who presented with a single testis in his scrotum after low
      impact perineal trauma, consistent with testicular dislocation. The literature
      regarding scrotal trauma includes few cases of testicular dislocation from low
      impact perineal trauma. Included is a brief review of the most recent data
      including epidemiology, differential diagnosis, acute management, and
      complications pertinent to the pediatric emergency clinician. 

PMID- 25373571
TI  - Untethering an unusual cause of kidney injury in a teenager with Down syndrome.
AB  - Acute kidney injury (AKI) is characterized by the acute nature and the inability
      of kidneys to maintain fluid homeostasis as well as adequate electrolyte and acid
      base balance, resulting in an accumulation of nitrogenous waste and elevation of
      serum blood urea nitrogen and creatinine values. Acute kidney injury may be a
      single isolated event, yet oftentimes, it results from an acute chronic kidney
      disease. It is critical to seek out the etiology of AKI and to promptly manage
      the underlying chronic kidney disease to prevent comorbidities and mortality that
      may ensue. We described a case of a 16-year-old adolescent girl with Down
      syndrome who presented with AKI and electrolyte aberrance.Abdominal and renal
      ultrasounds demonstrated a significantly dilated bladder as well as frank
      hydronephrosis and hydroureter bilaterally. Foley catheter was successful in
      relieving the obstruction and improving her renal function. However, a magnetic
      resonance imaging was pursued in light of her chronic constipation and back pain,
      and it revealed a structural defect (tethered cord) that underlies a chronic
      process that was highly likely contributory to her AKI. She was managed
      accordingly with a guarded result and required long-term and close monitoring. 

PMID- 25373572
TI  - Myocarditis.
AB  - Myocarditis is an inflammatory disease of the heart that can cause devastating
      disease in otherwise healthy children. Inciting agents such as viral infection
      cause direct damage to the myocardial cells, which triggers an inflammatory
      response that enhances myocardial toxicity and associated morbidity. Severe cases
      typically present with respiratory distress and cardiovascular collapse, whereas
      subclinical cases are unnoticed by the medical community. The initial workup in
      suspected cases should include an electrocardiogram, chest radiograph, and
      cardiac troponin T. Treatment is concentrated on hemodynamic stabilization with
      optimization of heart failure management, dysrhythmia protocol, and supportive
      therapy. The purpose of this review was to provide the emergency medicine
      practitioner a concise and current review of the basic pathophysiology as well as
      a functional and evidence-based approach to the diagnosis and treatment of
      myocarditis in the pediatric population. 

PMID- 25373574
TI  - Pulmonary embolism in the pediatric emergency department: a case demonstrating
      the application of point-of-care cardiac ultrasound in a pediatric patient with
      pulmonary embolism.
AB  - Although pulmonary embolism in children is rare, it is important for the
      pediatric emergency medicine provider to be aware of its presentation and
      emergent management. We present a case of bilateral pulmonary embolisms in an
      adolescent patient to illustrate the benefits from the timely diagnosis of right
      ventricular dysfunction by point-of-care echocardiography performed by emergency
      medicine physicians. Ultrasonographic techniques and the emergent management of
      pulmonary embolism are reviewed. 

PMID- 25373575
TI  - Neurogenic pulmonary edema.

PMID- 25373576
TI  - ECGs in the ED.

PMID- 25373577
TI  - Acute meningitis in the pediatric emergency department: diagnostic yield of
      procalcitonin and C-reactive protein.

PMID- 25373579
TI  - Image of the month: Gallbladder volvulus diagnosed with preoperative volume
      rendering three-dimensional drip-infusion CT cholangiography.

PMID- 25373582
TI  - Editorial: Bowel preparation: is fair good enough?
AB  - The effectiveness of colonoscopy in reducing colorectal cancer incidence and
      mortality has been shown to be associated with an endoscopist's adenoma detection
      rate, although the ability to detect adenomas depends, in part, on the quality of
      bowel preparation. Many endoscopists routinely recommend shorter examination
      intervals for colonoscopies with a fair or intermediate-quality bowel
      preparation, assuming that the preparation is insufficient for the purpose of
      colorectal cancer screening. In this issue, Clark et al. performed a systematic
      review and meta-analysis to assess the adequacy of a fair-quality bowel
      preparation, finding no difference in the adenoma detection rate of colonoscopies
      with an intermediate-quality bowel preparation relative to those with a high
      quality preparation. Although this finding has potentially significant
      implications for patient care and healthcare costs, the limitations of the
      adenoma detection rate as a performance measure and variability in the
      application of bowel preparation ratings are important issues that must be
      considered.

PMID- 25373585
TI  - Is fecal microbiota transplantation the answer for irritable bowel syndrome? A
      single-center experience.

PMID- 25373586
TI  - Esophageal symptoms are not related to abnormal motor function.

PMID- 25373587
TI  - Response to Meyer.

PMID- 25373588
TI  - Therapeutic modulation and reestablishment of the intestinal microbiota with
      fecal microbiota transplantation resolves sepsis and diarrhea in a patient.

PMID- 25373589
TI  - Evaluation of TNM status changes between the first two CT scans in patients with
      pancreatic cancer.

PMID- 25373590
TI  - At 64 years, Peutz-Jeghers syndrome is still in the differential!

PMID- 25373591
TI  - Therapy without diagnosis.

PMID- 25373592
TI  - The safety of probiotics in IBS and CIC is worthy of further discussion.

PMID- 25373594
TI  - Phenylalanine sensitive K562-D cells for the analysis of the biochemical impact
      of excess amino acid.
AB  - Although it is recognized that the abnormal accumulation of amino acid is a cause
      of the symptoms in metabolic disease such as phenylketonuria (PKU), the
      relationship between disease severity and serum amino acid levels is not well
      understood due to the lack of experimental model. Here, we present a novel in
      vitro cellular model using K562-D cells that proliferate slowly in the presence
      of excessive amount of phenylalanine within the clinically observed range, but
      not phenylpyruvate. The increased expression of the L-type amino acid transporter
      (LAT2) and its adapter protein 4F2 heavy chain appeared to be responsible for the
      higher sensitivity to phenylalanine in K562-D cells. Supplementation with valine
      over phenylalanine effectively restored cell proliferation, although other amino
      acids did not improve K562-D cell proliferation over phenylalanine. Biochemical
      analysis revealed mammalian target of rapamycin complex (mTORC) as a terminal
      target of phenylalanine in K562-D cell proliferation, and supplementation of
      valine restored mTORC1 activity. Our results show that K562-D cell can be a
      potent tool for the investigation of PKU at the molecular level and to explore
      new therapeutic approaches to the disease. 

PMID- 25373596
TI  - Trienamine-mediated asymmetric [4+2]-cycloaddition of alpha,beta-unsaturated
      ester surrogates applying 4-nitro-5-styrylisoxazoles.
AB  - Highly enantioselective organocatalytic [4+2]-cycloaddition of in situ generated
      trienamines with 4-nitro-5-styrylisoxazoles as alpha,beta-unsaturated ester
      surrogates is presented. The synthetic utility of this strategy is demonstrated
      by transforming the formed cycloadducts into optically active carboxylates. 

PMID- 25373595
TI  - Dyssynchronous pacing triggers endothelial-mesenchymal transition through
      heterogeneity of mechanical stretch in a canine model.
AB  - BACKGROUND: Endothelial-mesenchymal transition (EndMT) plays a pivotal role in
      cardiac fibrosis. However, it is unclear whether EndMT is involved in
      dyssynchronous heart failure (DHF). METHODS AND RESULTS: Twelve dogs received 3
      week rapid right ventricular pacing (RVP) to develop DHF and then were randomly
      divided into a RVP group (n=6; RVP for another 3 weeks) and a biventricular
      pacing (BiVP) group (n=6; BiVP for 3 weeks), and another 6 dogs were in the
      control group. Contractile function in BiVP group was a little better than that
      in RVP group (P<0.05), but significant heart failure remained in 2 groups. RVP
      induced more significant cardiac fibrosis and higher collagen 1A2 expression in
      the left ventricular lateral wall (late-contracting and high-stress) than that in
      the anterior wall, and for those in the BiVP group, it was much lower. CD31,
      S100A4, alpha-smooth muscle actin and collagen 1A2 were used to evaluate EndMT.
      EndMT levels, transforming growth factor-beta (TGF-beta)/snail signaling,
      collagen 1A2 and integrin beta1 expression were much higher in the endothelial
      cells from the RVP lateral wall than that from BiVP. In this in vitro study,
      cyclic stretch could independently induce EndMT and enhance the pro-EndMT effect
      of TGF-beta in HUVECs, which could be partly blocked by integrin beta1 siRNA.
      CONCLUSIONS: RVP-induced DHF could aggravate fibrosis due to regional
      heterogeneity of mechanical stress, and it was better in the BiVP group where
      mechanical stress-induced EndMT might play a pivotal role through the integrin
      beta1 pathway.

PMID- 25373597
TI  - Epithelial junctions, cytoskeleton, and polarity.
AB  - A distinctive feature of polarized epithelial cells is their specialized
      junctions, which contribute to cell integrity and provide platforms to
      orchestrate cell shape changes. This chapter discusses the composition, assembly
      and remodeling of C. elegans cell-cell (CeAJ) and hemidesmosome-like cell
      extracellular matrix junctions (CeHD), proteins that anchor the cytoskeleton, and
      mechanisms involved in establishing epithelial polarity. Major recent progress in
      this area has come from the analysis of mechanisms that maintain cell polarity,
      which involve lipids and trafficking, and on the impact of mechanical forces on
      junction remodeling. This chapter focuses on cellular, rather than developmental,
      aspects of epithelial cells. 

PMID- 25373598
TI  - 6-Substituted 1,2-benzoxathiine-2,2-dioxides are isoform-selective inhibitors of
      human carbonic anhydrases IX, XII and VA.
AB  - A series of 6-substituted 2-benzoxathiine-2,2-dioxides were synthesized starting
      from 2,5-dihydroxybenzaldehyde, and then screened in vitro for their inhibition
      properties against five human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. All
      the compounds showed excellent selectivity against the mitochondrial (hCA VA) and
      the tumor associated (hCA IX and XII) enzymes. 

PMID- 25373599
TI  - Safety limits for elements in toys: a comparison between the old and the new
      European toys safety directive.

PMID- 25373600
TI  - Mapracorat, a novel non-steroidal selective glucocorticoid receptor agonist for
      the treatment of allergic conjunctivitis.
AB  - Glucocorticoids are used to treat chronic and severe forms of allergic
      conjunctivitis. Although they exert a rapid and powerful therapeutic activity,
      relevant side effects may limit their ocular use: increase of intraocular
      pressure, cataract formation and reduced resistance to infections. New
      glucocorticoids displaying the same potency of classical glucocorticoids but with
      fewer adverse effects are needed for the treatment of ocular disorders.
      Mapracorat (also known as ZK245186 or BOL-303242-X) is a novel non-steroidal
      selective glucocorticoid receptor agonist that is in the first phases of clinical
      evaluation (Phase II Clinical trials) for topical treatment of inflammatory skin
      and ocular disorders. Mapracorat binds selectively to human glucocorticoid
      receptor and displays powerful anti-inflammatory effects. In experimental models
      of ocular diseases, mapracorat reduces clinical symptoms, eosinophil recruitment,
      chemokines and pro-inflammatory cytokines production at ocular level, confirming
      that it acts preventing both the early and late phase of allergic response.
      Interestingly, mapracorat induces a lower increase of intraocular pressure in
      comparison to the classical glucocorticoid dexamethasone. Several clinical trials
      are ongoing to investigate the efficacy and safety of mapracorat for the
      treatment of several ocular diseases. Transrepressive mechanisms are thought to
      account for the majority of mapracorat's antiinflammatory effects; however, the
      induction of anti-inflammatory proteins likely involved in transactivation events
      may contribute to mapracorat-mediated anti-inflammatory properties and deserve to
      be further investigated in suitable in vivo and in vitro models. These
      observations may influence how novel "differential" ligands are discovered,
      identified and evaluated. 

PMID- 25373601
TI  - Efficacy, quality of life, and acceptability outcomes of atypical antipsychotic
      augmentation treatment for treatment-resistant depression: protocol for a
      systematic review and network meta-analysis.
AB  - BACKGROUND: Major depressive disorder (MDD) is a debilitating and costly mental
      disorder. Although commercially available antidepressants have proliferated over
      the last 20 years, a substantial number of patients either do not respond
      adequately to these drugs or are unable to tolerate their adverse effects. One
      common approach has been to augment conventional antidepressants with an
      adjunctive agent, but the optimal selection of atypical antipsychotic agents for
      adjunctive treatment of treatment-resistant depression (TRD) remains
      controversial. METHODS/DESIGN: An electronic literature search of PubMed, the
      Cochrane Library, Embase, Web of Science, LiLACS, CINAHL, and PsycINFO for
      studies will be conducted with no restrictions on language, publication year, or
      publication type. Several clinical trial registry agencies, pharmaceutical
      company websites, and FDA reports will also be reviewed. Randomized clinical
      trials (RCTs) with atypical antipsychotic augmentation treatment for treatment
      resistant depression will be considered. Data will be independently extracted by
      two reviewers. Traditional pairwise meta-analyses will be performed for RCTs that
      directly compare different treatment arms. Then, Bayesian network meta-analyses
      will be performed to compare the relative efficacy and acceptability of different
      atypical antipsychotic agents (and doses). A sensitivity analysis will be
      performed by excluding studies classified as a small sample size, having a high
      placebo effect. DISCUSSION: This systematic review and network meta-analysis will
      comparatively analyze the efficacy, quality of life, and acceptability profiles
      of atypical antipsychotic medications used for the adjunctive treatment of TRD.
      The findings should provide clinically relevant implications for comprehensively
      understanding the risk-benefit profiles of these adjunctive treatments.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD 42014009666.

PMID- 25373602
TI  - The novel IkappaB kinase beta inhibitor IMD-0560 prevents bone invasion by oral
      squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) cells display significantly augmented nuclear
      factor-kappaB (NF-kappaB) activity, and inhibiting this activity suppresses
      malignant tumor characteristics. Thus, we evaluated the effect of IMD-0560, a
      novel inhibitor of IkappaB kinase (IKK) beta that is under assessment in a
      clinical trial of rheumatoid arthritis, on bone invasion by the mouse OSCC cell
      line SCCVII. We examined the inhibitory effects of IMD-0560 on NF-kappaB activity
      and tumor invasion using human OSCC cell lines and SCCVII cells in vitro. Using a
      mouse model of jaw bone invasion by SCCVII cells, we assessed the inhibitory
      effect of IMD-0560 on jaw bone invasion, tumor growth, and matrix degradation in
      vivo. IMD-0560 suppressed the nuclear translocation of NF-kappaB and the
      degradation of IkappaBalpha in OSCC cells. IMD-0560 also inhibited invasion by
      suppressing matrix metalloproteinase-9 (MMP-9) production in OSCC cells. IMD-0560
      protected against zygoma and mandible destruction by SCCVII cells, reduced the
      number of osteoclasts by inhibiting receptor activator of NF-kappaB ligand
      (RANKL) expression in osteoblastic cells and SCCVII cells, increased SCCVII cell
      death and suppressed cell proliferation and MMP-9 production in SCCVII cells.
      Based on these results, IMD-0560 may represent a new therapeutic agent for bone
      invasion by OSCC cells. 

PMID- 25373603
TI  - An ER-associated miRNA signature predicts prognosis in ER-positive breast cancer.
AB  - BACKGROUND: Breast cancer patients with positive estrogen receptor (ER) have a
      better prognosis. However, no prognostic miRNA signature was reported in the ER
      positive breast cancer. The aim of the study was to identify and assess the
      prognostic significance of a miRNA signature in ER-positive breast cancer.
      METHODS: Two cohorts from The Cancer Genome Atlas (TCGA) dataset were used as
      training (n =596) and testing set (n =319). Differential expression profiling was
      identified in the training set. And the prognostic value of the miRNA signature
      was then assessed in the two cohorts. RESULTS: A total of 14 miRNAs were observed
      to be associated with the status of ER by significance analysis of microarrays
      (SAM) in the training set. Patients were characterized as high score or low score
      group according to the calculated risk scores from each miRNA. And patients in
      high score group had worse overall survival compared with those in low score
      group both in the training and testing set. CONCLUSIONS: Our study revealed a
      miRNA signature including 14 miRNAs associated with ER status which could act as
      a prognostic marker in ER-positive breast cancer.

PMID- 25373604
TI  - Quantification of neurotoxin BMAA (beta-N-methylamino-L-alanine) in seafood from
      Swedish markets.
AB  - The neurotoxin beta-N-methylamino-L-alanine (BMAA) produced naturally by
      cyanobacteria, diatoms and dinoflagellates can be transferred and accumulated up
      the food chain, and may be a risk factor for neurodegenerative diseases. This
      study provides the first systematic screening of BMAA exposure of a large
      population through the consumption of seafood sold in metropolitan markets. BMAA
      was distinguished from known isomers by liquid chromatography tandem mass
      spectrometry after acidic hydrolysis and derivatization. Using deuterium-labeled
      internal standard, BMAA was quantified as 0.01-0.90 MUg/g wet weight of tissues
      in blue mussel, oyster, shrimp, plaice, char and herring, but was undetectable
      (<0.01 MUg/g) in other samples (salmon, cod, perch and crayfish). Provided that
      the content of BMAA detected is relevant for intake calculations, the data
      presented may be used for a first estimation of BMAA exposure through seafood
      from Swedish markets, and to refine the design of future toxicological
      experiments and assessments.

PMID- 25373605
TI  - A comparison of posterior lumbar interbody fusion and transforaminal lumbar
      interbody fusion: a literature review and meta-analysis.
AB  - BACKGROUND: We compared the perioperative results and complications associated
      with PLIF and TLIF, and collected evidence for choosing the better fusion method.
      METHODS: A literature survey of the MEDLINE and EMBASE databases identified 7
      comparative observational studies that met our inclusion criteria. Checklists by
      Cowley were used to evaluate the risk of bias of the included studies. A database
      including patient demographic information, perioperative results, and
      complications was established. The summary odds ratio and weighed mean difference
      with 95% confidence interval were calculated with a random-effects model.
      RESULTS: We found that PLIF had a higher complication rate (P <0.00001), and TLIF
      reduced the rate of durotomy (P = 0.01). No statistical difference was found
      between the two groups with regard to clinical satisfaction (P = 0.54), blood
      loss (P = 0.14), vertebral root injury (P = 0.08), graft malposition (P = 0.06),
      infection (P = 0.36), or rate of radiographic fusion (P = 0.27). The evidence
      indicated that PLIF required longer operative time (P = 0.03). CONCLUSIONS: The
      evidence indicated that TLIF could reduce the complication rate and durotomy.
      Neither TLIP nor PLIF was found superior in terms of clinical satisfaction or
      radiographic fusion rate. PLIF might result in longer time in surgery.

PMID- 25373607
TI  - Exploring the decomposition pathways of iron asymmetric transfer hydrogenation
      catalysts.
AB  - Our group has developed a series of iron-based asymmetric transfer hydrogenation
      (ATH) catalysts for the reduction of polar double bonds. The activation of the
      precatalysts as well as the catalytic mechanism have been thoroughly
      investigated, but the decomposition pathways of these systems are poorly
      understood. Herein, we report a study of the deactivation pathways for an iron
      ATH catalyst under catalytically relevant conditions. The decomposition pathways
      were examined using experimental techniques and density functional theory (DFT)
      calculations. The major decomposition products that formed,
      Fe(CO)((Et)2PCH2CH2CHCHNCH2CH2P(Et)2) (3a) and
      Fe(CO)((Et)2PCH2CH2C(Ph)C(Ph)NCH2CH2P(Et)2) (3b), had two amido donors as well as
      a C=C bond on the diamine backbone of the tetradentate ligand. These species were
      identified by NMR studies and one was isolated as a bimetallic complex with
      Ru(II)Cp*. Two minor iron hydride species also formed concurrently with 3a, as
      determined by NMR studies, one of which was isolated and contained a fully
      saturated ligand as well as a hydride ligand. None of the compounds that were
      isolated were found to be active ATH catalysts.

PMID- 25373606
TI  - Influence of mycosporine-like amino acids and gadusol on the rheology and Raman
      spectroscopy of polymer gels.
AB  - BACKGROUND: The amphiphilic nature of polymers allows them to be widely
      incorporated as carriers in different pharmaceutical applications since they are
      able to work as vehicles for hydro- or lipo-soluble actives. OBJECTIVE: The aim
      of this study was to determine the rheological behavior and vibrational spectral
      variations of two hydrophilic gels prepared with Poloxamer 407 (PO) or Pluronic F
      127 (PL) with the addition of the actives mycosporine-like amino acids and
      gadusol. METHODS: The structures of these polymers in two different
      concentrations (20% w/w and 27% w/w) were characterized by rheological studies
      and Raman spectroscopy. RESULTS: Gels prepared with higher polymer concentration
      showed larger G' (storage modulus) values. The C-C stretch and the CH2 rocking
      predominated in the gels containing PL (20% w/w) and this correlated with a less
      viscous behavior. The mixture of the actives induced higher contributions of
      Raman peaks related to trans conformation of the C-C bonds located in hydrophilic
      polymer blocks, whereas the same peaks decreased in the sample containing only
      gadusol. CONCLUSIONS: Larger tensile strength and elastic component were observed
      upon increasing polymer concentration, thus evidencing polymer-polymer and/or
      polymer-polymer-actives interactions. The presence of the actives affected the
      mechanical properties of the polymer gels. Gadusol particularly seems to alter
      the conformation of the polymer chains by favoring gauche orientations, in
      parallel with rising viscoelastic parameters. More stretched arrangements of the
      polymer are probably induced in the presence of larger concentration of actives,
      due to specific interactions with their hydrophilic groups.

PMID- 25373608
TI  - What is the evidence for the use of corticosteroids in migraine?
AB  - Corticosteroids are widely prescribed for the management of migraine attacks. The
      earliest clinical studies examining the efficacy of corticosteroid monotherapy
      for managing migraine attacks date back to 1952. Since then, 26 heterogeneous
      clinical studies and four meta-analyses have been conducted to assess the
      efficacy of corticosteroids in either aborting acute migraine attacks, prolonged
      migraine attacks or recurrent headaches. Most of these (86 %) studies employed
      different comparator arms with corticosteroids monotherapy administration while
      some studies (14 %) evaluated adjunctive corticosteroid therapy. The majority of
      these clinical studies revealed the superior efficacy of corticosteroids as mono-
      or adjunctive-therapy both for recurrent and acute migraine attacks, while the
      remaining showed non-inferior efficacy. Different forms of oral and parenteral
      corticosteroids in either single-dose or short-tapering schedules are prescribed;
      there are clinical studies supporting the efficacy of both methods.
      Corticosteroids can be administered safely up to six times annually.
      Corticosteroids are also useful in managing patients who frequent emergency
      departments with "medication-seeking behavior." Migraine patients with refractory
      headaches, history of recurrent headaches, severe baseline disability, and status
      migrainosus were found to have the most beneficial response from corticosteroid
      therapy. 

PMID- 25373609
TI  - What can pharmacists' do about the Medicare Part D Donut hole and reimbursement?
      A six-state survey.
AB  - BACKGROUND: While Medicare Part D was signed into law in 2003 and initiated in
      2006, there is a scarcity of information related to the implications of Part D on
      community pharmacies and subsequent effects. OBJECTIVE: To determine the
      financial implications of Part D on community pharmacy, to identify pharmacists'
      and beneficiaries concerns from the pharmacists' perspective and to determine the
      pharmacists' responses to these impactions and concerns. METHODS: A cross
      sectional survey of pharmacists practicing in six states (Maine, New Jersey, New
      York, Maryland, Massachusetts and Pennsylvania) was conducted online between June
      and December 2011. The 37-question online survey collected demographic data, data
      about implications of Part D on community pharmacy and patients, and pharmacists'
      beliefs about ideal pharmacy practice and Part D plans. RESULTS: Of the 4,888
      online surveys, only 1,108 were assumed to have reached the intended recipients
      (response rate 25 %). Fifty-six percent reported that reimbursement was the most
      significant concern, and 34.5 % of the owners or part-owners were planning to
      close their pharmacy due to financial pressures exerted by Part D. A significant
      relationship was observed between dispensing of 90 days' supply of medications
      and better financial performance (chi (2) = 6.95, p = 0.0084). The most
      significant patient concerns were formulary and copayment (52.8 %) and Donut hole
      (52.4 %). Fifty-four percent respondents stated that his/her pharmacy helped
      patients obtain financial assistance while patients were in the Donut hole.
      CONCLUSION: Respondents were most concerned about the poor reimbursement rates,
      but pharmacists who dispensed 90 day supply of medications reported acceptable
      financial performance. Pharmacists also reported helping patients obtain
      financial assistance while in the Donut hole.

PMID- 25373610
TI  - Performance on fast- and usual-paced 400-m walk tests in older adults: are they
      comparable?
AB  - BACKGROUND AND AIMS: Fast- and usual-paced 400-m walking tests are often used to
      assess physical fitness or function, respectively, though it is not known how
      performance converges on these tests. This study aims to determine whether
      performance on the fast- and usual-paced 400-m walks varies based upon age and
      physical function. METHODS: Participants (26 men, 38 women aged 70-92) completed
      a fast- and usual-paced 400-m walk. The Short Physical Performance Battery was
      used to assess function (score range 0-12). Body mass index and health history
      were also assessed. RESULTS: Finish times for the fast- and usual-paced 400-m
      walks were 333.3 and 380.3 s, respectively (P < 0.0001), and highly correlated (r
      = 0.88, P < 0.001). Higher functioning participants (SPPB > 10) had greater
      differences between tests compared to lower functioning participants (SPPB <= 10)
      (52.9 vs. 26.2 s, P = 0.005), as did younger participants (age < 80) compared to
      those age 80 and older (56.8 vs. 32.8 s, P = 0.003). DISCUSSION: Older and lower
      functioning participants had greater convergence on the fast- and usual-paced 400
      m walks. Potentially some of these lower functioning and older adults may have
      already performed at their maximal capacity during the usual-paced walk, while
      the younger and higher functioning participants were able to walk substantially
      faster when asked. CONCLUSIONS: Choice of walking test should consider the age
      and functional capacity of the population as well as whether function or fitness
      is of interest.

PMID- 25373611
TI  - Infection risk factors associated with seropositivity for Toxoplasma gondii in a
      population-based study in the Central Region, Ghana.
AB  - About 20-90% of the world's population has had contact with Toxoplasma gondii
      parasites. The aim of this study was to determine the seroprevalence and risk
      factors associated with T. gondii infection in the Central Region, Ghana. A
      community-based cross-sectional study was conducted in three selected
      communities. Serum samples were tested for the presence of anti-T. gondii IgG and
      IgM antibodies by ELISA. A serological criterion for seropositivity was a
      positive test result for any of the two anti-Toxoplasma IgG or IgM antibodies or
      a combination of both. In all, 390 participants of mean age 47.0 years consisting
      of 118 (30.%) males and 272 (69.7%) females were tested. The overall
      seroprevalence of T. gondii was 85% (333/390) where fishermen, farmers and
      fishmongers, respectively, had the highest seropositivity. IgG and IgM antibodies
      were detected in 329 (84%) and 25 (6%), respectively, while both IgG and IgM
      antibodies were detected in 21 (5%) of the participants. Respectively, 1% (4/390)
      and 79% (308/390) of participants tested positive for IgM-only and IgG-only
      antibodies. There was a significant relationship between Toxoplasma
      seropositivity and contact with soil, presence of a cat in the surrounding area,
      age, sources of drinking water, level of formal education, and socioeconomic
      status. The results suggest that the seashore may serve as a good ground for
      sporulation and survival of Toxoplasma oocysts.

PMID- 25373612
TI  - Pre-operative cellularity mapping and intra-MRI surgery: potential for improving
      neurosurgical biopsies.
AB  - Stereotactic biopsies are frequently performed to secure definitive diagnosis for
      brain tumor patients. Fundamentally, there are two major difficulties in these
      endeavors. First, because of intra-tumoral heterogeneity inherent in many forms
      of brain cancer, biopsies taken from one region may yield a different diagnosis
      than if another area is biopsied. Second, stereotactic needle biopsies inherently
      rely on mathematical algorithms for targeting, without real-time visualization of
      the actual biopsy site. This article describes the novel MRI-based technologies
      that can potentially afford neurosurgeons the opportunity to address these
      challenges. 

PMID- 25373613
TI  - Longevity of Daphnia and the attenuation of stress responses by melatonin.
AB  - BACKGROUND: The widespread occurrence of melatonin in prokaryotes as well as
      eukaryotes indicates that this indoleamine is considerably old. This high
      evolutionary age has led to the development of diverse functions of melatonin in
      different organisms, such as the detoxification of reactive oxygen species and
      anti-stress effects. In insects, i.e. Drosophila, the addition of melatonin has
      also been shown to increase the life span of this arthropod, probably by reducing
      age-related increasing oxidative stress. Although the presence of melatonin was
      recently found to exist in the ecological and toxicological model organism
      Daphnia, its function in this cladoceran has thus far not been addressed.
      Therefore, we challenged Daphnia with three different stressors in order to
      investigate potential stress-response attenuating effects of melatonin. i) Female
      and male daphnids were exposed to melatonin in a longevity experiment, ii)
      Daphnia were confronted with stress signals from the invertebrate predator
      Chaoborus sp., and iii) Daphnia were grown in high densities, i.e. under crowding
      stress conditions. RESULTS: In our experiments we were able to show that
      longevity of daphnids was not affected by melatonin. Therefore, age-related
      increasing oxidative stress was probably not compensated by added melatonin.
      However, melatonin significantly attenuated Daphnia's response to acute predator
      stress, i.e. the formation of neckteeth which decrease the ability of the gape
      limited predator Chaoborus sp. to handle their prey. In addition, melatonin
      decreased the extent of crowding-related production of resting eggs of Daphnia.
      CONCLUSIONS: Our results confirm the effect of melatonin on inhibition of stress
      signal responses of Daphnia. Until now, only a single study demonstrated
      melatonin effects on behavioral responses due to vertebrate kairomones, whereas
      we clearly show a more general effect of melatonin: i) on morphological predator
      defense induced by an invertebrate kairomone and ii) on life history
      characteristics transmitted by chemical cues from conspecifics. Therefore, we
      could generally confirm that melatonin plays a role in the attenuation of
      responses to different stressors in Daphnia.

PMID- 25373616
TI  - Hepatitis C virus infection treatment: An era of game changer direct acting
      antivirals and novel treatment strategies.
AB  - Chronic hepatitis C virus infection and associated liver diseases represent a
      major health care burden all over the world. The current standard of care, i.e.
      peginterferon-alfa (PEG-IFNalpha) plus ribavirin (RBV) are associated with
      frequent and sometimes serious adverse effects and contraindications, which
      further limit their therapeutic efficacy. The approval of first and second
      generation HCV protease inhibitors represents a major breakthrough in the
      development of novel direct acting antivirals (DAAs) against different HCV
      genotypes and establishes a new standard of care for chronically infected HCV
      genotypes 1 patients. Similarly, next generation protease inhibitors and HCV RNA
      polymerase inhibitors have shown better pharmacokinetics and pharmacodynamics in
      terms of broader HCV genotypes coverage, better safety profile, fewer drug
      interactions and possible once daily administration than first generation direct
      acting antivirals. The testing of adenovirus-based vector vaccines, which
      escalates the innate and acquired immune responses against the most conserved
      regions of the HCV genome in chimpanzees and humans, may be a promising
      therapeutic approach against HCV infection in coming future. This review article
      presents up-to-date knowledge and recent developments in HCV therapeutics,
      insights the shortcomings of current HCV therapies and key lessons from the
      therapeutic potential of improved anti-HCV treatment strategies. 

PMID- 25373614
TI  - Genome-wide analysis in Plasmodium falciparum reveals early and late phases of
      RNA polymerase II occupancy during the infectious cycle.
AB  - BACKGROUND: Over the course of its intraerythrocytic developmental cycle (IDC),
      the malaria parasite Plasmodium falciparum tightly orchestrates the rise and fall
      of transcript levels for hundreds of genes. Considerable debate has focused on
      the relative importance of transcriptional versus post-transcriptional processes
      in the regulation of transcript levels. Enzymatically active forms of RNAPII in
      other organisms have been associated with phosphorylation on the serines at
      positions 2 and 5 of the heptad repeats within the C-terminal domain (CTD) of
      RNAPII. We reasoned that insight into the contribution of transcriptional
      mechanisms to gene expression in P. falciparum could be obtained by comparing the
      presence of enzymatically active forms of RNAPII at multiple genes with the
      abundance of their associated transcripts. RESULTS: We exploited the
      phosphorylation state of the CTD to detect enzymatically active forms of RNAPII
      at most P. falciparum genes across the IDC. We raised highly specific monoclonal
      antibodies against three forms of the parasite CTD, namely unphosphorylated, Ser5
      P and Ser2/5-P, and used these in ChIP-on-chip type experiments to map the genome
      wide occupancy of RNAPII. Our data reveal that the IDC is divided into early and
      late phases of RNAPII occupancy evident from simple bi-phasic RNAPII binding
      profiles. By comparison to mRNA abundance, we identified sub-sets of genes with
      high occupancy by enzymatically active forms of RNAPII and relatively low
      transcript levels and vice versa. We further show that the presence of active and
      repressive histone modifications correlates with RNAPII occupancy over the IDC.
      CONCLUSIONS: The simple early/late occupancy by RNAPII cannot account for the
      complex dynamics of mRNA accumulation over the IDC, suggesting a major role for
      mechanisms acting downstream of RNAPII occupancy in the control of gene
      expression in this parasite.

PMID- 25373617
TI  - Plasmodium berghei circumsporozoite protein encapsulated in oligomannose-coated
      liposomes confers protection against sporozoite infection in mice.
AB  - BACKGROUND: The design and development of an effective malaria vaccine against
      the pre-erythrocytic and erythrocytic-stages of infection present a great
      challenge. METHODS: In the present study, protective efficacy of oligomannose
      coated liposome (OML)-entrapped merozoite and sporozoite antigens against
      Plasmodium berghei challenge infection in BALB/c mice was evaluated. RESULTS:
      Subcutaneous immunization with truncated merozoite surface protein 1 entrapped
      with OML (OML-PbMSP1) prolonged survival, but failed to protect the mice from
      erythrocytic-stage infection, despite the antigen-specific antibody responses
      induced by the immunization regimen. In contrast, immunization with
      circumsporozoite protein entrapped with OML (OML-PbCSP) elicited antigen-specific
      humoral and cellular responses, which correlated with substantial protection
      against sporozoite challenge infections. CONCLUSIONS: The current results
      represent the use of an oligomannose-coated liposome-based vaccine against pre
      erythrocytic and erythrocytic stages malaria infection. This approach may offer a
      new vaccination strategy against malaria infection.

PMID- 25373618
TI  - Analysis of COQ2 gene in multiple system atrophy.
AB  - BACKGROUND: Loss of function COQ2 mutations results in primary CoQ10 deficiency.
      Recently, recessive mutations of the COQ2 gene have been identified in two
      unrelated Japanese families with multiple system atrophy (MSA). It has also been
      proposed that specific heterozygous variants in the COQ2 gene may confer
      susceptibility to sporadic MSA. To assess the frequency of COQ2 variants in
      patients with MSA, we sequenced the entire coding region and investigated all
      exonic copy number variants of the COQ2 gene in 97 pathologically-confirmed and
      58 clinically-diagnosed MSA patients from the United States. RESULTS: We did not
      find any homozygous or compound heterozygous pathogenic COQ2 mutations including
      deletion or multiplication within our series of MSA patients. In two patients, we
      identified two heterozygous COQ2 variants (p.S54W and c.403 + 10G > T) of unknown
      significance, which were not observed in 360 control subjects. We also identified
      one heterozygous carrier of a known loss of function p.S146N substitution in a
      severe MSA-C pathologically-confirmed patient. CONCLUSIONS: The COQ2 p.S146N
      substitution has been previously reported as a pathogenic mutation in primary
      CoQ10 deficiency (including infantile multisystem disorder) in a recessive
      manner. This variant is the third primary CoQ10 deficiency mutation observed in
      an MSA case (p.R387X and p.R197H). Therefore it is possible that in the
      heterozygous state it may increase susceptibility to MSA. Further studies,
      including reassessing family history in patients of primary CoQ10 deficiency for
      the possible occurrence of MSA, are now warranted to resolve the role of COQ2
      variation in MSA.

PMID- 25373619
TI  - Interleukin-10 protects against atherosclerosis by modulating multiple
      atherogenic macrophage function.
AB  - Atherosclerosis is primarily a disorder of lipid metabolism, but there is also a
      prominent chronic inflammatory component that drives the atherosclerotic lesion
      progression in the artery wall. During hyperlipidaemic conditions, there is a
      rapid influx of circulating monocytes into the atherosclerosis-prone areas of the
      arterial intima. These infiltrated monocytes differentiate into macrophages and
      take up the atherogenic lipoproteins in the intima of the vessel wall that have
      been modified within the lesion environment. Interleukin (IL)-10 is a prototypic
      anti-inflammatory cytokine made primarily by the macrophages and Th2 subtype T
      lymphocytes. In terms of atherosclerosis its major roles include inhibition of
      macrophage activation as well as inhibition of matrix metalloproteinase, pro
      inflammatory cytokines and cyclooxygenase-2 expression in lipid-loaded and
      activated macrophage foam cells. Recent discoveries suggest another important
      role of IL-10 in atherosclerosis: its ability to alter lipid metabolism in
      macrophages. The current review will highlight the present knowledge on multiple
      ways in which IL-10 mediates atherosclerosis. As macrophages play a critical role
      in all stages of atherosclerosis, the review will concentrate on how IL-10
      regulates the activities of macrophages that are especially important in the
      development of atherosclerosis. 

PMID- 25373621
TI  - The statistical reporting quality of articles published in 2010 in five dental
      journals.
AB  - OBJECTIVES: Statistical methods play an important role in medical and dental
      research. In earlier studies it has been observed that current use of methods and
      reporting of statistics are responsible for some of the errors in the
      interpretation of results. The aim of this study was to investigate the quality
      of statistical reporting in dental research articles. METHODS: A total of 200
      articles published in 2010 were analysed covering five dental journals: Journal
      of Dental Research, Caries Research, Community Dentistry and Oral Epidemiology,
      Journal of Dentistry and Acta Odontologica Scandinavica. Each paper underwent
      careful scrutiny for the use of statistical methods and reporting. A paper with
      at least one poor reporting item has been classified as 'problems with reporting
      statistics' and a paper without any poor reporting item as 'acceptable'. RESULTS:
      The investigation showed that 18 (9%) papers were acceptable and 182 (91%) papers
      contained at least one poor reporting item. CONCLUSIONS: The proportion of at
      least one poor reporting item in this survey was high (91%). The authors of
      dental journals should be encouraged to improve the statistical section of their
      research articles and to present the results in such a way that it is in line
      with the policy and presentation of the leading dental journals.

PMID- 25373620
TI  - Rectified directional sensing in long-range cell migration.
AB  - How spatial and temporal information are integrated to determine the direction of
      cell migration remains poorly understood. Here, by precise microfluidics
      emulation of dynamic chemoattractant waves, we demonstrate that, in
      Dictyostelium, directional movement as well as activation of small guanosine
      triphosphatase Ras at the leading edge is suppressed when the chemoattractant
      concentration is decreasing over time. This 'rectification' of directional
      sensing occurs only at an intermediate range of wave speed and does not require
      phosphoinositide-3-kinase or F-actin. From modelling analysis, we show that
      rectification arises naturally in a single-layered incoherent feedforward circuit
      with zero-order ultrasensitivity. The required stimulus time-window predicts ~5 s
      transient for directional sensing response close to Ras activation and inhibitor
      diffusion typical for protein in the cytosol. We suggest that the ability of
      Dictyostelium cells to move only in the wavefront is closely associated with
      rectification of adaptive response combined with local activation and global
      inhibition. 

PMID- 25373622
TI  - Relationship between cotinine and trans-3'-hydroxycotinine glucuronidation and
      the nicotine metabolite ratio in Caucasian smokers.
AB  - CONTEXT: Nicotine metabolite ratio (NMR) is linked with smoking behaviour and
      quitting, but little is known about the importance of UDP-glucuronosyltransferase
      metabolism phenotype on NMR. OBJECTIVE: To investigate the relationship between
      NMR and UDP-glucuronosyltransferase phenotype in a Caucasian population. METHODS:
      Urine samples from 260 smokers were measured by UPLC-MS/MS for cotinine (COT), 3'
      hydroxycotinine, COT-glucuronide and 3'-hydroxycotinine-glucuronide. UDP
      glucuronosyltransferase phenotype was assessed using the proportion of
      metabolites present as the glucuronide. RESULTS: A correlation was found between
      NMR and UDP-glucuronosyltransferase phenotype for COT (males and females) and 3'
      HC in females (p < 0.0001). CONCLUSION: NMR is clearly influenced by UDP
      glucuronosyltransferase phenotype for COT in Caucasians.

PMID- 25373624
TI  - Double-layered ZnO nanostructures for efficient perovskite solar cells.
AB  - To date, a single layer of TiO2 or ZnO has been the most successful
      implementations of any electron transport layer (ETL) in solution-processed
      perovskite solar cells. In a quest to improve the ETL, we explore a new
      nanostructured double-layer ZnO film for mesoscopic perovskite-based thin film
      photovoltaics. This approach yields a maximum power conversion efficiency of
      10.35%, which we attribute to the morphology of oxide layer and to faster
      electron transport. The successful implementation of the low-temperature
      hydrothermally processed double-layer ZnO film as ETL in perovskite solar cells
      highlights the opportunities to further improve the efficiencies by focusing on
      the ETL in this rapidly developing field. 

PMID- 25373625
TI  - Efficacy of ultraviolet sterilization of liquid nitrogen.

PMID- 25373623
TI  - Beclin 1 biology and its role in heart disease.
AB  - Macroautophagy (hereafter termed autophagy) is a highly evolutionarily conserved
      pathway that degrades intracellular components such as damaged organelles in
      lysosome. Autophagy occurs at low basal levels in virtually all types of cells,
      which is required for the maintenance of cellular homeostasis. Beclin 1 protein,
      encoded by the beclin 1 gene, plays a central role in the regulation of
      autophagy. Beclin 1 primarily functions as a scaffolding protein assembling
      Beclin 1 interactome to regulate Class III PI3K/VPS34 activity, which in turn,
      tightly controls autophagy at multiple stages. In addition to autophagy, Beclin 1
      participates in the regulation of other biological processes such as endocytosis,
      apoptosis and phagocytosis. Fine-tuning of Beclin 1 protein levels, intracellular
      localization and the assembly of its interactome is pivotal for the proper
      execution of these biological functions. Deregulation of Beclin 1 contributes to
      the pathogenesis of a variety of human diseases. In this review, we summarize
      biology of Beclin 1 and its role in human pathology, with an emphasis on heart
      disease. 

PMID- 25373626
TI  - Response: Efficacy of ultraviolet sterilization of liquid nitrogen.

PMID- 25373627
TI  - Methamphetamine psychosis: epidemiology and management.
AB  - Psychotic symptoms and syndromes are frequently experienced among individuals who
      use methamphetamine, with recent estimates of up to approximately 40 % of users
      affected. Although transient in a large proportion of users, acute symptoms can
      include agitation, violence, and delusions, and may require management in an
      inpatient psychiatric or other crisis intervention setting. In a subset of
      individuals, psychosis can recur and persist and may be difficult to distinguish
      from a primary psychotic disorder such as schizophrenia. Differential diagnosis
      of primary vs. substance-induced psychotic disorders among methamphetamine users
      is challenging; nevertheless, with careful assessment of the temporal
      relationship of symptoms to methamphetamine use, aided by state-of-the art
      psychodiagnostic assessment instruments and use of objective indicators of recent
      substance use (i.e., urine toxicology assays), coupled with collateral clinical
      data gathered from the family or others close to the individual, diagnostic
      accuracy can be optimized and the individual can be appropriately matched to a
      plan of treatment. The pharmacological treatment of acute methamphetamine-induced
      psychosis may include the use of antipsychotic medications as well as
      benzodiazepines, although symptoms may resolve without pharmacological treatment
      if the user is able to achieve a period of abstinence from methamphetamine.
      Importantly, psychosocial treatment for methamphetamine dependence has a strong
      evidence base and is the optimal first-line treatment approach to reducing rates
      of psychosis among individuals who use methamphetamines. Prevention of
      methamphetamine relapse is the most direct means of preventing recurrence of
      psychotic symptoms and syndromes. Long-term management of individuals presenting
      with recurrent and persistent psychosis, even in the absence of methamphetamine
      use, may include both behavioral treatment to prevent resumption of
      methamphetamine use and pharmacological treatment targeting psychotic symptoms.
      In addition, treatment of co-occurring psychiatric disorders including depression
      and anxiety is important as a means of preventing relapse to methamphetamine use,
      which is often triggered by associated symptoms.

PMID- 25373628
TI  - Comment on: "Perispinal Etanercept for Post-Stroke Neurological and Cognitive
      Dysfunction: Scientific Rationale and Current Evidence".

PMID- 25373631
TI  - Virtual screening of potential inhibitor against FtsZ protein from Staphylococcus
      aureus.
AB  - The gram-positive bacterium Staphylococcus aureus, responsible for a wide variety
      of diseases in human involve all organ systems ranging from localized skin
      infections to life-threatening systemic infections. FtsZ, the key protein of
      bacterial cell division was selected as a potent anti bacterial target. In order
      to identify the new compounds structure based screening process was carried out.
      An enrichment study was performed to select a suitable scoring function and to
      retrieve potential candidates against FtsZ from a large chemical database. The
      docking score and docking energy values were compared and their atomic
      interaction was also evaluated. Furthermore molecular dynamics simulation were
      also been performed to check the stability and the amino acids interacted towards
      the FtsZ. Finally we selected C ID 16284, 25916, 15894, 13403 as better lead
      compounds. From these results, we conclude that our insilico results will provide
      a framework for the detailed in vitro and in vivo studies about the FtsZ protein
      activity in drug development process.

PMID- 25373630
TI  - A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein E4
      carriers with mild-moderate Alzheimer's disease.
AB  - INTRODUCTION: Intranasal (IN) insulin acutely improves verbal memory in mild
      cognitive impairment (MCI)/Alzheimer's disease (AD), but its therapeutic effects
      may be attenuated in apolipoprotein E4 (ApoE4) carriers. Furthermore, rapid
      acting (RA) insulins may have superior therapeutic effects compared with regular
      insulin types. OBJECTIVES: To measure the safety and efficacy of intranasally
      delivered RA glulisine in ApoE4 carriers with mild-moderate AD. METHODS: We
      performed a double-blinded, randomized, cross-over study of RA insulin glulisine
      in nine mild-moderate AD subjects to better understand the relationship between
      RA insulin, ApoE4 carrier status and memory performance. RESULTS: IN glulisine
      was well tolerated but failed to have an acute impact on cognition in ApoE4
      carriers with AD. Serum insulin levels acutely dropped following treatment, but
      peripheral glucose levels remained unchanged. CONCLUSION: Larger clinical trials
      of longer duration are necessary to better understand the relationships between
      RA insulin, ApoE4 carrier status and cognitive performance in AD.

PMID- 25373632
TI  - Molecular dynamics simulation studies of the wild type and E92Q/N155H mutant of
      Elvitegravir-resistance HIV-1 integrase.
AB  - Although Elvitegravir (EVG) is a newly developed antiretrovirals drug to treat
      the acquired immunodeficiency syndrome (AIDS), drug resistance has already been
      found in clinic, such as E92Q/N155H and Q148H/G140S. Several structural
      investigations have already been reported to reveal the molecular mechanism of
      the drug resistance. As full length crystal structure for HIV-1 integrase is
      still unsolved, we herein use the crystal structure of the full length prototype
      foamy virus (PFV) in complex with virus DNA and inhibitor Elvitegravir as a
      template to construct the wild type and E92Q/N155H mutant system of HIV-1
      integrase. Molecular dynamic simulations was used to revel the binding mode and
      the drug resistance of the EVG ligand in E92Q/N155H. Several important
      interactions were discovered between the mutated residues and the residues in the
      active site of the E92Q/N155H double mutant pattern, and cross correlation and
      clustering methods were used for detailed analysis. The results from the MD
      simulation studies will be used to guide the experimental efforts of developing
      novel inhibitors against drug-resistant HIV integrase mutants.

PMID- 25373629
TI  - Authors' reply to Whitlock: Perispinal etanercept for post-stroke neurological
      and cognitive dysfunction: scientific rationale and current evidence.

PMID- 25373633
TI  - Design of potential RNAi (miRNA and siRNA) molecules for Middle East respiratory
      syndrome coronavirus (MERS-CoV) gene silencing by computational method.
AB  - The Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that
      manifests itself in viral infection with fever, cough, shortness of breath, renal
      failure and severe acute pneumonia, which often result in a fatal outcome. MERS
      CoV has been shown to spread between people who are in close contact.
      Transmission from infected patients to healthcare personnel has also been
      observed and is irredeemable with present technology. Genetic studies on MERS-CoV
      have shown that ORF 1ab encodes replicase polyproteins and play a foremost role
      in viral infection. Therefore, ORF 1ab replicase polyprotein may be used as
      suitable target for disease control. Viral activity can be controlled by RNA
      interference (RNAi) technology, a leading method for post transcriptional gene
      silencing in a sequence specific manner. However, there is a genetic
      inconsistency in different viral isolates; it is a great challenge to design
      potential RNAi (miRNA and siRNA) molecules which can silence the respective
      target genes rather than any other viral gene simultaneously. In current study
      four effective miRNA and five siRNA molecules for silencing of nine different
      strains of MERS-CoV were rationally designed and corroborated using computational
      methods, which might lead to knockdown the activity of virus. siRNA and miRNA
      molecules were predicted against ORF1ab gene of different strains of MERS-CoV as
      effective candidate using computational methods. Thus, this method may provide an
      insight for the chemical synthesis of antiviral RNA molecule for the treatment of
      MERS-CoV, at genomic level.

PMID- 25373634
TI  - In silico elucidation and inhibition studies of selected phytoligands against
      Mitogen activated protein kinases of protozoan parasites.
AB  - Parasitic MAPKs exhibiting significant divergence with humans and playing an
      imperative role in parasitic metabolic activities have been exploited from
      several years as important targets for development of novel therapeutics. In
      addition, the emergence of the drug resistant variants of parasitic diseases in
      the recent years has aroused a great need for the development of potent
      inhibitors against them. In the present study we selected the metabolically
      active MAPKs LmxMPK4, PfMAP2 and TbMAPK5 of the three parasitic protozoans
      Leishmania mexicana, Plasmodium falciparum and Trypanosoma brucei respectively.
      The homology modeling technique was used to develop the 3D structures of these
      proteins and the same was validated by PROCHECK, ERRAT, ProQ and ProSA web
      servers to check the reliability. Ten phytoligands were employed for molecular
      docking studies with these proteins to search for potent phytoligand as a broad
      spectrum inhibitor. In this regard two phytoligands (Aspidocarpine for LmxMPK4 &
      TbMAPK5 and Cubebin for PfMAP2) were found to be more effective inhibitors, in
      term of robust binding energy, strong inhibition constant and better interactions
      between protein-ligand complexes. Furthermore predicted ADME & Toxicity
      properties suggested that these identified phytoligands exhibited comparable
      results to control drugs potentiating them as persuasive therapeutic agents for
      Leishmania, Trypanosoma and Plasmodium sp.

PMID- 25373635
TI  - Magnetic nanoparticles-loaded Physarum polycephalum: Directed growth and
      particles distribution.
AB  - Slime mold Physarum polycephalum is a single cell visible by an unaided eye. The
      slime mold optimizes its network of protoplasmic tubes to minimize expose to
      repellents and maximize expose to attractants and to make efficient
      transportation of nutrients. These properties of P. polycephalum, together with
      simplicity of its handling and culturing, make it a priceless substrate for
      designing novel sensing, computing and actuating architectures in living
      amorphous biological substrate. We demonstrate that, by loading Physarum with
      magnetic particles and positioning it in a magnetic field, we can, in principle,
      impose analog control procedures to precisely route active growing zones of slime
      mold and shape topology of its protoplasmic networks.

PMID- 25373636
TI  - Journals unite for reproducibility.

PMID- 25373637
TI  - On the mend.

PMID- 25373638
TI  - Protect the parks.

PMID- 25373639
TI  - Metascience could rescue the 'replication crisis'.

PMID- 25373651
TI  - Fledgling space industry resolute after fatal crash.

PMID- 25373652
TI  - Future of Great Barrier Reef divides scientists.

PMID- 25373653
TI  - Ministers promise basket of gifts for German science.

PMID- 25373654
TI  - Models overestimate Ebola cases.

PMID- 25373655
TI  - Lobbying sways NIH grants.

PMID- 25373657
TI  - University sued after firing creationist fossil hunter.

PMID- 25373658
TI  - After the Berlin Wall: Central Europe up close.

PMID- 25373659
TI  - Working together: A call for inclusive conservation.

PMID- 25373660
TI  - Conservation: A to-do list for the world's parks.

PMID- 25373661
TI  - Economics: Account for depreciation of natural capital.

PMID- 25373665
TI  - Navigation Nobel: Soviet pioneer.

PMID- 25373666
TI  - Biodiversity: Reap the benefits of the Nagoya Protocol.

PMID- 25373667
TI  - India: Endangered species damned by dams.

PMID- 25373668
TI  - Navigation Nobel: Ways to help the lost.

PMID- 25373669
TI  - Accelerator physics: Surf's up at SLAC.

PMID- 25373670
TI  - Astrophysics: Monster star found hiding in plain sight.

PMID- 25373672
TI  - Organic chemistry: Shape control in reactions with light.

PMID- 25373673
TI  - Sustainable ecosystems and society.

PMID- 25373674
TI  - Implications of agricultural transitions and urbanization for ecosystem services.
AB  - Historically, farmers and hunter-gatherers relied directly on ecosystem services,
      which they both exploited and enjoyed. Urban populations still rely on
      ecosystems, but prioritize non-ecosystem services (socioeconomic). Population
      growth and densification increase the scale and change the nature of both
      ecosystem- and non-ecosystem-service supply and demand, weakening direct
      feedbacks between ecosystems and societies and potentially pushing social
      ecological systems into traps that can lead to collapse. The interacting and
      mutually reinforcing processes of technological change, population growth and
      urbanization contribute to over-exploitation of ecosystems through complex
      feedbacks that have important implications for sustainable resource use. 

PMID- 25373675
TI  - Learning to coexist with wildfire.
AB  - The impacts of escalating wildfire in many regions - the lives and homes lost,
      the expense of suppression and the damage to ecosystem services - necessitate a
      more sustainable coexistence with wildfire. Climate change and continued
      development on fire-prone landscapes will only compound current problems.
      Emerging strategies for managing ecosystems and mitigating risks to human
      communities provide some hope, although greater recognition of their inherent
      variation and links is crucial. Without a more integrated framework, fire will
      never operate as a natural ecosystem process, and the impact on society will
      continue to grow. A more coordinated approach to risk management and land-use
      planning in these coupled systems is needed. 

PMID- 25373676
TI  - The performance and potential of protected areas.
AB  - Originally conceived to conserve iconic landscapes and wildlife, protected areas
      are now expected to achieve an increasingly diverse set of conservation, social
      and economic objectives. The amount of land and sea designated as formally
      protected has markedly increased over the past century, but there is still a
      major shortfall in political commitments to enhance the coverage and
      effectiveness of protected areas. Financial support for protected areas is
      dwarfed by the benefits that they provide, but these returns depend on effective
      management. A step change involving increased recognition, funding, planning and
      enforcement is urgently needed if protected areas are going to fulfil their
      potential. 

PMID- 25373677
TI  - Life cycles, fitness decoupling and the evolution of multicellularity.
AB  - Cooperation is central to the emergence of multicellular life; however, the means
      by which the earliest collectives (groups of cells) maintained integrity in the
      face of destructive cheating types is unclear. One idea posits cheats as a
      primitive germ line in a life cycle that facilitates collective reproduction.
      Here we describe an experiment in which simple cooperating lineages of bacteria
      were propagated under a selective regime that rewarded collective-level
      persistence. Collectives reproduced via life cycles that either embraced, or
      purged, cheating types. When embraced, the life cycle alternated between
      phenotypic states. Selection fostered inception of a developmental switch that
      underpinned the emergence of collectives whose fitness, during the course of
      evolution, became decoupled from the fitness of constituent cells. Such
      development and decoupling did not occur when groups reproduced via a cheat
      purging regime. Our findings capture key events in the evolution of Darwinian
      individuality during the transition from single cells to multicellularity. 

PMID- 25373678
TI  - High-efficiency acceleration of an electron beam in a plasma wakefield
      accelerator.
AB  - High-efficiency acceleration of charged particle beams at high gradients of
      energy gain per unit length is necessary to achieve an affordable and compact
      high-energy collider. The plasma wakefield accelerator is one concept being
      developed for this purpose. In plasma wakefield acceleration, a charge-density
      wake with high accelerating fields is driven by the passage of an ultra
      relativistic bunch of charged particles (the drive bunch) through a plasma. If a
      second bunch of relativistic electrons (the trailing bunch) with sufficient
      charge follows in the wake of the drive bunch at an appropriate distance, it can
      be efficiently accelerated to high energy. Previous experiments using just a
      single 42-gigaelectronvolt drive bunch have accelerated electrons with a
      continuous energy spectrum and a maximum energy of up to 85 gigaelectronvolts
      from the tail of the same bunch in less than a metre of plasma. However, the
      total charge of these accelerated electrons was insufficient to extract a
      substantial amount of energy from the wake. Here we report high-efficiency
      acceleration of a discrete trailing bunch of electrons that contains sufficient
      charge to extract a substantial amount of energy from the high-gradient,
      nonlinear plasma wakefield accelerator. Specifically, we show the acceleration of
      about 74 picocoulombs of charge contained in the core of the trailing bunch in an
      accelerating gradient of about 4.4 gigavolts per metre. These core particles gain
      about 1.6 gigaelectronvolts of energy per particle, with a final energy spread as
      low as 0.7 per cent (2.0 per cent on average), and an energy-transfer efficiency
      from the wake to the bunch that can exceed 30 per cent (17.7 per cent on
      average). This acceleration of a distinct bunch of electrons containing a
      substantial charge and having a small energy spread with both a high accelerating
      gradient and a high energy-transfer efficiency represents a milestone in the
      development of plasma wakefield acceleration into a compact and affordable
      accelerator technology. 

PMID- 25373679
TI  - Asymmetric photoredox transition-metal catalysis activated by visible light.
AB  - Asymmetric catalysis is seen as one of the most economical strategies to satisfy
      the growing demand for enantiomerically pure small molecules in the fine chemical
      and pharmaceutical industries. And visible light has been recognized as an
      environmentally friendly and sustainable form of energy for triggering chemical
      transformations and catalytic chemical processes. For these reasons, visible
      light-driven catalytic asymmetric chemistry is a subject of enormous current
      interest. Photoredox catalysis provides the opportunity to generate highly
      reactive radical ion intermediates with often unusual or unconventional
      reactivities under surprisingly mild reaction conditions. In such systems,
      photoactivated sensitizers initiate a single electron transfer from (or to) a
      closed-shell organic molecule to produce radical cations or radical anions whose
      reactivities are then exploited for interesting or unusual chemical
      transformations. However, the high reactivity of photoexcited substrates,
      intermediate radical ions or radicals, and the low activation barriers for follow
      up reactions provide significant hurdles for the development of efficient
      catalytic photochemical processes that work under stereochemical control and
      provide chiral molecules in an asymmetric fashion. Here we report a highly
      efficient asymmetric catalyst that uses visible light for the necessary molecular
      activation, thereby combining asymmetric catalysis and photocatalysis. We show
      that a chiral iridium complex can serve as a sensitizer for photoredox catalysis
      and at the same time provide very effective asymmetric induction for the
      enantioselective alkylation of 2-acyl imidazoles. This new asymmetric photoredox
      catalyst, in which the metal centre simultaneously serves as the exclusive source
      of chirality, the catalytically active Lewis acid centre, and the photoredox
      centre, offers new opportunities for the 'green' synthesis of non-racemic chiral
      molecules. 

PMID- 25373681
TI  - Interactive notebooks: Sharing the code.

PMID- 25373680
TI  - Recent Northern Hemisphere stratospheric HCl increase due to atmospheric
      circulation changes.
AB  - The abundance of chlorine in the Earth's atmosphere increased considerably during
      the 1970s to 1990s, following large emissions of anthropogenic long-lived
      chlorine-containing source gases, notably the chlorofluorocarbons. The chemical
      inertness of chlorofluorocarbons allows their transport and mixing throughout the
      troposphere on a global scale, before they reach the stratosphere where they
      release chlorine atoms that cause ozone depletion. The large ozone loss over
      Antarctica was the key observation that stimulated the definition and signing in
      1987 of the Montreal Protocol, an international treaty establishing a schedule to
      reduce the production of the major chlorine- and bromine-containing halocarbons.
      Owing to its implementation, the near-surface total chlorine concentration showed
      a maximum in 1993, followed by a decrease of half a per cent to one per cent per
      year, in line with expectations. Remote-sensing data have revealed a peak in
      stratospheric chlorine after 1996, then a decrease of close to one per cent per
      year, in agreement with the surface observations of the chlorine source gases and
      model calculations. Here we present ground-based and satellite data that show a
      recent and significant increase, at the 2sigma level, in hydrogen chloride (HCl),
      the main stratospheric chlorine reservoir, starting around 2007 in the lower
      stratosphere of the Northern Hemisphere, in contrast with the ongoing monotonic
      decrease of near-surface source gases. Using model simulations, we attribute this
      trend anomaly to a slowdown in the Northern Hemisphere atmospheric circulation,
      occurring over several consecutive years, transporting more aged air to the lower
      stratosphere, and characterized by a larger relative conversion of source gases
      to HCl. This short-term dynamical variability will also affect other
      stratospheric tracers and needs to be accounted for when studying the evolution
      of the stratospheric ozone layer. 

PMID- 25373684
TI  - Parent and adolescent effects of a universal group program for the parenting of
      adolescents.
AB  - There is growing support for the large-scale implementation of parenting programs
      for the prevention of child behavior disorders and child maltreatment in younger
      children. However, there is only limited evidence on the efficacy of parenting
      programs in modifying risk and protective factors relating to adolescent behavior
      problems. This study examined the efficacy of Group Teen Triple P (GTTP), an
      eight-session parenting program specifically designed for parents of young
      adolescents. Seventy-two families with adolescents aged between 12 and 15 years
      were randomly assigned to either GTTP (n = 35) or a care as usual (CAU) control
      condition (n = 37). Compared to CAU parents, parents who received GTTP reported
      significant improvements in parenting practices, parenting confidence, the
      quality of family relationships, and fewer adolescent problem behaviors at post
      intervention. Several of the parent-reported effects were corroborated by reports
      from adolescents, including decreases in parent-adolescent conflict and increases
      in parental monitoring. Adolescents whose parents participated in GTTP also
      reported significantly fewer behavioral problems than adolescents in the CAU
      condition. Many of these improvements were maintained at 6-month follow-up.

PMID- 25373685
TI  - Pedestrian injuries-related deaths: a global evaluation.
AB  - OBJECTIVE: Pedestrians are vulnerable road users who are at risk of injuries and
      death on the roads. We aimed to define factors affecting pedestrian injuries
      related deaths worldwide and to give recommendations regarding their prevention
      priorities. METHODS: Data on pedestrian injuries-related deaths for years 2007
      and 2010 were retrieved from the WHO global status reports on road safety. These
      included the country population, gross national income (GNI), number of
      registered vehicles, estimated pedestrian deaths rate, effectiveness of
      enforcement of law, and the presence of policies to promote walking or cycling.
      Correlations between studied variables were done using Spearman rank correlation.
      General linear models were used to define factors affecting pedestrian injuries
      related deaths. RESULTS: The median (range) pedestrian death rates of different
      countries per 100,000 population significantly decreased in year 2010 compared
      with year 2007 [3.9 (0-13.5) compared with 4.2 (0-23.6), (p = 0.004, Wilcoxon
      signed rank test)]. There was a reduction of 8.1% of the global pedestrian death
      rate between 2007 and 2010. The estimated pedestrian lives saved annually
      worldwide of a population of 6.8 billion were 23,120 persons. A general linear
      model has shown that GNI (p = 0.001) and population density (p = 0.01) were the
      best predictors of pedestrian death rates in 2007, while national legislation (p
      = 0.03) was the best predictor of pedestrian death rates in 2010. CONCLUSIONS:
      There is a change in the factors affecting pedestrian mortality worldwide over
      time. GNI and population density became less significant than national
      legislation enforcement. Legislation and its enforcement are important to achieve
      the UN mission of reducing road traffic deaths by 5 million over the next decade.

PMID- 25373686
TI  - Time trends in method-specific suicide rates in Japan, 1990-2011.
AB  - BACKGROUND: Little is known about whether particular suicide methods have
      contributed differently to the recent unfavourable suicide mortality trends in
      Japan. Analysing such trends may shed light on the effect of potentially
      preventable factors, such as the impact of restricting access to certain popular
      suicide methods, on overall rates. Therefore, we assessed recent trends in method
      specific suicide by gender and age in Japan. METHOD: Suicide mortality and
      population data between 1990 and 2011 were obtained from the Vital Statistics of
      Japan and used to calculate method-specific mortality rates. Suicide methods were
      divided into seven groups: overdose, gases, hanging, drowning, cutting, jumping
      and other means. Age was divided into four groups: 15-24, 25-44, 45-64 and 65+
      years. We applied joinpoint regression to the data and quantified the observed
      changes. RESULTS: The results of the joinpoint regression analyses showed a sharp
      increase in overall suicide rates for males and females of all ages until the
      late 1990s. Suicide from hanging and jumping, in particular, contributed to this
      increase. After 2000, an increasing trend in overall suicide rates in both males
      and females aged 15-24 and 25-44 years was observed, with overdose, gases and
      hanging contributing to this increasing trend. CONCLUSIONS: Our findings revealed
      that different suicide methods varied in their contribution to the recent overall
      suicide transition in Japan. Regarding factors associated with the recent
      increase in suicides by overdose, gases, hanging and jumping, further research is
      needed in order to promote and implement effective means restriction strategies.

PMID- 25373687
TI  - Advances in MR image-guided high-intensity focused ultrasound therapy.
AB  - The clinical role of magnetic resonance image-guided high-intensity focused
      ultrasound (MR-HIFU) is rapidly expanding due to its merit of non-invasiveness.
      MR thermometry based on a proton resonance frequency shift technique is able to
      accurately measure HIFU-induced temperature changes, which provides considerable
      advantages over ultrasonography-guided HIFU in terms of safety and therapeutic
      efficacy. Recent studies and the resulting technological advances in MR-HIFU such
      as MR thermometry for moving organs, MR-acoustic radiation force imaging, and a
      volumetric mild hyperthermia technique further will expand its clinical roles
      from mere ablation therapy to targeted drug delivery and chemo- or radio
      sensitisation for cancer treatment. In this article, MR-HIFU therapy is
      comprehensively reviewed with an emphasis on the roles of MR imaging in HIFU
      therapy, techniques of MR monitoring, recent advances in clinical MR-HIFU
      systems, and potential future applications of MR-HIFU therapy. In addition, the
      pros and cons of MR-HIFU when compared with ultrasonography-guided HIFU are
      discussed. 

PMID- 25373688
TI  - Effect of GaAIAs low-level laser therapy on the healing of human palate mucosa
      after connective tissue graft harvesting: randomized clinical trial.
AB  - Among the available techniques to treat gingival recession, connective tissue
      graft (CTG) presents more foreseeability and better results in the long term.
      However, this technique causes morbidity and discomfort in the palatine region
      due to graft removal at that site. The aim of this clinical trial was to evaluate
      the influence of low-level laser therapy (LLLT) on the healing of the donor
      palatine area after CTG. Thirty-two patients presenting buccal gingival recession
      were selected and randomly assigned to receive LLLT irradiation (test group) or
      LLLT sham (control group) in the palatine area after connective graft removal. A
      diode laser (AsGaAl, 660 nm) was applied to test the sites immediately after
      surgery and every other day for 7 days. The evaluated parameters were wound
      remaining area (WRA), scar and tissue colorimetry (TC), tissue thickness (TT),
      and postoperative discomfort (D). These parameters were evaluated at baseline and
      7, 14, 45, 60, and 90 days after surgery. Two-way repeated measures ANOVA was
      used for analysis. The test group presented statistically significant smaller
      wounds at days 14 and 45. None of the patients presented a scar at the operated
      area, and colorimetry analysis revealed that there was no statistically
      significant difference between groups (p > 0.05). Patients reported mild to
      moderate discomfort, with low consumption of analgesic pills. We concluded that
      LLLT irradiation can accelerate wound healing on palatine mucosa after connective
      tissue removal for root coverage techniques (ClinicalTrial.org NCT02239042). 

PMID- 25373689
TI  - Involvement of Toll-like receptors in cervical cancer susceptibility among
      Tunisian women.
AB  - Previous studies underscored the importance of genetic factors in the
      pathogenesis of certain cancers, including cervical cancer. Epidemiological
      evidence supports an association between specific polymorphisms of Toll-like
      receptors (TLR) with several human pathological states, including cervical
      cancer. The aim of this study was to investigate the link between specific gene
      variants in TLR2 (-196 to -174 del), TLR3 (c.1377 C>T), TLR4 (Asp299Gly), and
      TLR9 (2848 G>A) and susceptibility to cervical cancer in Tunisian women. Study
      subjects comprised 122 women with histopathologically-confirmed cervical cancer,
      and 260 unrelated age- and ethnically-matched healthy females, who served as
      controls. TLR genotyping was done using PCR-restriction fragment length
      polymorphism. The C/C genotype of TLR3 (c.1377 C>T) is associated with cervical
      cancer susceptibility (OR: 1.71, CI: 1.08-2.70). For TLR4 (Asp299Gly), the
      Asp/Asp genotype and the Asp allele were associated with higher risk of
      developing cervical cancer (OR: 4.95, CI: 1.97-13.22) and (OR: 5.17, CI: 2.11
      13.50) respectively. We demonstrated no association between the TLR2 (-196 to 
      174 del) and the TLR 9 (2848 G>A) polymorphisms and the susceptibility of
      cervical cancer among Tunisian women. However, the C/C genotype for the TLR3
      (c.1377 C>T) polymorphism and the Asp/Asp genotype and the Asp allele for
      (Asp299Gly) TLR4 polymorphism were found to be associated with a higher risk of
      cervical cancer.

PMID- 25373690
TI  - [Experimental program personalized care in patients with head and neck cancer].
AB  - OBJECTIVE: Describe the implementation and preliminary results of the
      "Experimental Program Personalized care" in patients with Head and Neck cancer.
      MATERIALS AND METHODS: After being selected a graduate nurse status, called
      coordination, participated in the development of forms of detection needs and
      concerns of patients, in collaboration with various health professionals.
      RESULTS: Between January 2011 and December 2012, 200 new patients with head and
      neck cancer were included: 62% with advanced cancer and 38% of early stage. No
      patient refused to participate in this experiment. At least one consultation with
      a psychiatrist was necessary for 82% of patients with advanced cancer. Social
      problems were the second axis of the needs of patients. CONCLUSION: By
      identifying the needs of patients and organizing their support, this evaluation
      optimizes not only the therapeutic care for the patient but also the management
      of human resources within the team.

PMID- 25373691
TI  - [Use of guidelines and heterogeneity of decision making for adjuvant chemotherapy
      in hormone-receptor positive, HER2-negative, early breast cancer: results of a
      French national survey].
AB  - Adjuvant chemotherapy for localised breast cancer aims at reducing the risk of
      relapse and at increasing overall survival. Decision criteria include tumour
      burden and biological profile. It appears currently difficult to evaluate the
      benefit/risk ratio in certain borderline cases, which are more and more frequent.
      We have evaluated through an anonymous web survey conducted as part of the 2013
      Annual Saint-Paul-de-Vence breast conference, the chemotherapy decisions, use of
      guidelines and level of certainty with decisions in this type of situation
      through four clinical cases. The survey was proposed to 1,190 French physicians
      who are directly in charge of breast cancer care, whatever their specialty. Three
      hundred and fifty-three of them replied, of whom 67 % were oncologists and 15 %
      surgeons. A significantly heterogeneous decision was observed for two out of four
      cases, in which 52 and 69 % of the physicians opted for adjuvant chemotherapy,
      versus 48 and 21 % for abstention respectively. Eighty seven percent of
      responding physicians used guidelines to guide their decision. These guidelines
      were regional for 63 %, national for 36 %, local in 21 % and international in 16
      % of the cases. The level of certainty varied with clinical cases but not with
      the physician's specialty, nor type of decision.

PMID- 25373692
TI  - [Modalities of management of cancer patients with febrile neutropenia in the
      oncology emergency unit of Gustave-Roussy and their related costs].
AB  - BACKGROUND: Febrile neutropenia (FN) is a severe chemotherapy side effect.
      Hospitalization is recommended for FN episode of high-risk (HR) of complications.
      Management of FN at lower risk of complications remains unclear. METHODS: This is
      a prospective observation study in patients with solid tumors admitted to the
      emergency department FN. Collected data included demographics, clinical,
      biological, therapeutic costs, MASCC score and complications. RESULTS: Hundred
      and thirty-seven consecutive FN were recorded in 128 patients. Twenty-six FN
      (19%) were managed at home (all of them had a MASCC score >= 21); 111 (81%) were
      treated at hospital of which 37 NF were at HR of complications based on clinical
      and biological parameters (all of them had a MASCC score < 21) and for 74 of them
      the admission could be discussed (MASCC < 20 or >= 20). This group of patients
      was considerate with intermediate risk (IR). All IR patients were treated with
      the same antibiotics than outpatients, i.e. ceftriaxone in 36 cases (49%) or
      amoxicillin/clavulanic acid and ciprofloxacin in 38 cases (51%). For these 74
      cases, any severe complication was recorded. Antibiotics were adapted for only
      12% of these patients according to bacteriology results. CONCLUSION: This study
      showed the limits of the MASCC score. We did not observe any severe complications
      in patients admitted to the hospital according to clinical and biological
      parameters and with the high risk score MASCC. This study had some methodological
      bias but it allowed us to estimate the cost of the different ways of management
      and the difficulties to decide the hospitalization in FN.

PMID- 25373693
TI  - [Young medical oncologists: what training? For what professional identity?].
AB  - Medical oncology, which post-graduate diploma was established in France in 1984,
      was built on the practice of anticancer chemotherapy and interdisciplinarity. The
      political impetus of the Cancer Plan 2009-2013 had helped develop and generalize
      its learning since 2011. These recent changes explain the lack of information we
      have on the socialization of young medical oncologists in their discipline. To
      fill this gap, a qualitative exploratory study was conducted by comprehensive
      interviews with ten young medical oncologists. It revealed the importance of the
      physician patient relationship and clinical research in choosing this specialty.
      It also updated the large part of empowerment in the learning process.
      Furthermore, although the overall management often appears in the discourse of
      young oncologists, representation they have boils down to successive intervention
      of health professionals. The lack of specific training on this main concept in
      oncology appears to be missing in their vision of health coordination. Finally,
      the lack of training of consultation activities seems to be an important factor
      in the difficulty of projecting a private practice.

PMID- 25373694
TI  - [Reconstruction following shoulder resection for bone tumor].
AB  - Scapula and proximal humerus are the most frequent site of primary bone tumors of
      upper limb. Surgical reconstruction after resection, aimed to obtain a stable
      painful limb and active motion of the shoulder. Three major key-points can affect
      functional results: intra- or extra-articular resection, ability to offer a
      strength fixation of rotator cuff tendons, and remaining function of the deltoid
      muscle after resection. When most of the deltoid muscle is active associated with
      an intra-articular resection, recent results of reversed prosthesis are very
      promising in terms of active motion. For other cases, conventional or tumor
      prosthesis can be proposed, but inefficience of rotator cuff tendons fixation on
      a prosthesis leads to very poor restoration of active motion. Arthrodesis is an
      attractive option in this situation for young patients. In all cases, impairment
      of the shoulder function is the rule after resection, complication rate is high,
      and long-term deterioration of the reconstruction is frequent. Moreover, cosmetic
      results are always poor. 

PMID- 25373695
TI  - [Immunohistochemistry and personalised medicine in lung oncology: advantages and
      limitations].
AB  - The concept of personalized or stratified medicine in thoracic oncology have led
      to the development of companion diagnostic testing in the laboratories in order
      to detect genomic alterations which can be targeted by therapeutic molecules. The
      use of these companion tests has to be associated with an optimized quality
      control with the aim of getting solid results before treatment administration to
      the patients. The great majority of these tests is based on molecular biology
      approach. However, since the commercial availability of different antibodies
      targeting genomic alterations which can be used in formalin fixed paraffin
      sections, an alternative method to the molecular approach is the
      immunohistochemistry (IHC). Some of these antibodies are or will be probably soon
      used in a daily routine practice (such as anti-ALK or anti-MET antibodies). Other
      antibodies have currently a more restricted use in thoracic oncology (such as
      anti-BRAF V600E, anti-ROS1 and mutation-specific anti-EGFR antibodies). In this
      review, we aim to detail the advantages and the limits of IHC method in thoracic
      oncology field for personalized medicine, in particular comparatively to the
      molecular biology technology. Moreover, we discuss the opportunity to provide
      accredited IHC tests in the context of stratified medicine for lung cancer
      patients. 

PMID- 25373696
TI  - [Pediatric pheochromocytoma and paraganglioma: an update].
AB  - Pheochromocytomas and paragangliomas (PHEO/PGL) are neuroendocrine tumors that
      arise from sympathetic and parasympathetic paraganglia. Although well described
      in the adult population, diagnosis and treatment of these exceptionally rare
      neoplasms remains poorly characterized in children. This article reviews recent
      advances in clinical presentation, genetics, biochemistry, imaging and treatment
      of children with benign or malignant PHEO/PGL. Compared to adults, pediatric
      PHEO/PGL are more frequently familial, bilateral, multifocal and malignant.
      Approximately 50% of pediatric PHEO/PGL are associated with a mutation of one of
      the 12 known susceptibility genes. Von Hippel-Lindau disease, type 1
      neurofibromatosis, type 2 multiple endocrine neoplasia and familial PGL syndrome
      are hereditary tumor syndromes associated with an increased risk of developing
      such diseases. Clinical presentation includes symptoms related to catecholamine
      hypersecretion and/or tumor mass effect. Plasma and/or urine metanephrine dosages
      are recommended as first-line diagnostic biochemical tests. Magnetic resonance
      imaging is useful as initial radiological approach. Most pediatric PHEO/PGLs are
      benign. Surgical resection, with appropriate perioperative management of
      catecholamine-related symptoms, remains the treatment of choice. In case of
      metastatic disease, surgical removal of metastases when possible and I-131-MIBG
      radiotherapy provide limited results whereas chemotherapy is reserved for more
      advanced stages.

PMID- 25373697
TI  - [Axitinib in metastatic renal carcinomas: update of knowledge about side
      effects].
AB  - PURPOSE: The objective of this article is to summarize the knowledge as for the
      side effects related to axitinib in terms of incidence, etiology and symptoms for
      the effects requiring a specific management. METHODS: This article follows upon
      the recommendations for the clinical practice, published in 2011, which detailed
      the management of secondary specific toxicities related to targeted therapies
      prescribed for the treatment of metastatic renal cell carcinoma with a focus on
      axitinib. SYNTHESIS: Overall, the toxicity profile of axitinib is better the
      other tyrosine kinase inhibitors. The ENT side effects and polycythemia, which
      had not been initially described with other molecules, seem more frequent.
      Regarding management and follow-up of side effects with axitinib, as for the
      other targeted therapies used in metastatic renal carcinoma, there are no crucial
      changes since the recommendations of 2011. CONCLUSION: The management of side
      effects remains similar to the recommendations published in 2011. Only preventive
      measures and management of ENT side effects and polycythemia must be integrated
      in new thesaurus.

PMID- 25373699
TI  - Effects of enamel matrix genes on dental caries are moderated by fluoride
      exposures.
AB  - Dental caries (tooth decay) is the most common chronic disease, worldwide,
      affecting most children and adults. Though dental caries is highly heritable, few
      caries-related genes have been discovered. We investigated whether 18 genetic
      variants in the group of non-amelogenin enamel matrix genes (AMBN, ENAM, TUFT1,
      and TFIP11) were associated with dental caries experience in 13 age- and race
      stratified samples from six parent studies (N = 3,600). Linear regression was
      used to model genetic associations and test gene-by-fluoride interaction effects
      for two sources of fluoride: daily tooth brushing and home water fluoride
      concentration. Meta-analysis was used to combine results across five child and
      eight adult samples. We observed the statistically significant association of
      rs2337359 upstream of TUFT1 with dental caries experience via meta-analysis
      across adult samples (p < 0.002) and the suggestive association for multiple
      variants in TFIP11 across child samples (p < 0.05). Moreover, we discovered two
      genetic variants (rs2337359 upstream of TUFT1 and missense rs7439186 in AMBN)
      involved in gene-by-fluoride interactions. For each interaction, participants
      with the risk allele/genotype exhibited greater dental caries experience only if
      they were not exposed to the source of fluoride. Altogether, these results
      confirm that variation in enamel matrix genes contributes to individual
      differences in dental caries liability, and demonstrate that the effects of these
      genes may be moderated by protective fluoride exposures. In short, genes may
      exert greater influence on dental caries in unprotected environments, or
      equivalently, the protective effects of fluoride may obviate the effects of
      genetic risk alleles. 

PMID- 25373698
TI  - Loss-of-function mutation in the X-linked TBX22 promoter disrupts an ETS-1
      binding site and leads to cleft palate.
AB  - The cleft palate only (CPO) is a common congenital defect with complex etiology
      in humans. The molecular etiology of the CPO remains unknown. Here, we report a
      loss-of-function mutation in X-linked TBX22 gene (T-box 22) in a six-generation
      family of the CPO with obvious phenotypes of both cleft palate and hyper-nasal
      speech. We identify a functional -73G>A mutation in the promoter of TBX22, which
      is located at the core-binding site of transcription factor ETS-1 (v-ets avian
      erythroblastosis virus E26 oncogene homolog 1). Phylogenetic analysis showed that
      the sequence around the -73G>A mutation site is specific in primates. The
      mutation was detected in all five affected male members cosegregating with the
      affected phenotype and heterozygote occurred only in some unaffected females of
      the family, suggesting an X-linked transmission of the mutation in the family.
      The -73G>A variant is a novel single nucleotide mutation. Cell co-transfections
      indicated that ETS-1 could activate the TBX22 promoter. Moreover, EMSA and ChIP
      assays demonstrated that the allele A disrupts the binding site of ETS-1, thus
      markedly decreases the activity of the TBX22 promoter, which is likely to lead to
      the birth defect of the CPO without ankyloglossia. These results suggest that a
      loss-of-function mutation in the X-linked TBX22 promoter may cause the cleft
      palate through disruption of TBX22-ETS-1 pathway. 

PMID- 25373700
TI  - Native, living tissues as cell seeded scaffolds.
AB  - Much effort is expended in developing biomimetic scaffolds that provide the micro
      architecture of native tissue with appropriate cellular niches. Such scaffolds
      are often seeded with progenitor cells to generate engineered replacements for
      diseased or damaged tissues. An alternative approach relies on biology, rather
      than technology, to provide scaffolds containing progenitor cells in authentic
      niches. This article describes the use of accessible living tissues containing
      endogenous progenitor cells in their native, physiological environments. Such
      tissues also possess scaffolding properties, and can be readily harvested,
      manipulated and returned to the patient intra-operatively to facilitate repair
      and regeneration. Our group has explored the in situ genetic manipulation of
      cells within these tissues before they are reimplanted, although other means of
      modulation are certainly possible. Examples of suitable donor tissues include
      marrow, skeletal muscle and fat. In the case of marrow, clotting produces a
      moldable, autologous fibrin matrix containing endogenous cells; if necessary,
      exogenous cells can be added prior to clotting. These approaches have been
      studied experimentally in orthopaedic contexts, particularly for the healing and
      regeneration of bone and cartilage.

PMID- 25373701
TI  - Effective selenium detoxification in the seed proteins of a hyperaccumulator
      plant: the analysis of selenium-containing proteins of monkeypot nut (Lecythis
      minor) seeds.
AB  - A shotgun proteomic approach was applied to characterize the selenium (Se)
      containing proteins of the selenium hyperaccumulator monkeypot nut (Lecythis
      minor) seeds. The exceptionally high Se content (>4,000 mg kg(-1)) of the sample
      enabled a straightforward procedure without the need for multiple
      preconcentration and fractionation steps. The proteins identified were sulfur
      rich seed proteins, namely, 11S globulin (Q84ND2), 2S albumin (B6EU54), 2S sulfur
      rich seed storage proteins (P04403 and P0C8Y8) and a 11S globulin-like protein
      (A0EM48). Database directed search for theoretically selenium-containing peptides
      was assisted by manual spectra evaluation to achieve around 25% coverage on
      sulfur analogues. Remarkable detoxification mechanisms on the proteome level were
      revealed in the form of multiple selenomethionine-methionine substitution and the
      lack of selenocysteine residues. The degree of selenomethionine substitution
      could be characterized by an exponential function that implies the inhibition of
      protein elongation by selenomethionine. Our results contribute to the deeper
      understanding of selenium detoxification procedures in hyperaccumulator plants.

PMID- 25373702
TI  - Estimate of the penetrance of BRCA mutation and the COS software for the
      assessment of BRCA mutation probability.
AB  - We have designed the user-friendly COS software with the intent to improve
      estimation of the probability of a family carrying a deleterious BRCA gene
      mutation. The COS software is similar to the widely-used Bayesian-based BRCAPRO
      software, but it incorporates improved assumptions on cancer incidence in women
      with and without a deleterious mutation, takes into account relatives up to the
      fourth degree and allows researchers to consider an hypothetical third gene or a
      polygenic model of inheritance. Since breast cancer incidence and penetrance
      increase over generations, we estimated birth-cohort-specific incidence and
      penetrance curves. We estimated breast and ovarian cancer penetrance in 384 BRCA1
      and 229 BRCA2 mutated families. We tested the COS performance in 436 Italian
      breast/ovarian cancer families including 79 with BRCA1 and 27 with BRCA2
      mutations. The area under receiver operator curve (AUROC) was 84.4 %. The best
      probability threshold for offering the test was 22.9 %, with sensitivity 80.2 %
      and specificity 80.3 %. Notwithstanding very different assumptions, COS results
      were similar to BRCAPRO v6.0. 

PMID- 25373703
TI  - Selection of the surgical approach for reoperation of adult choledochal cysts.
AB  - BACKGROUND/PURPOSE: Our purpose was to evaluate the reasons for reoperations and
      outcomes in patients with choledochal cysts (CCs). METHODS: The records of
      patients with CCs who underwent reoperations from 1995 to 2012 were
      retrospectively reviewed. RESULTS: Of 165 patients with a mean age of 42.54 +/-
      14.05 years, 62 had Todani type I (37.6 %), 84 type IV-A (50.9 %), and 19 had
      unknown type CCs (11.5 %). Previous surgery was internal or external drainage
      alone in 66.1 % of patients with type I and 23.8 % of patients with type IV-A
      CCs. Partial cyst excision and Roux-en-Y cyst-jejunostomy or cyst excision and
      choledochoplasty by jejunal interposition were performed in 16.1 and 11.3 % of
      patients with type I and IV-A CCs, respectively. Reoperations at our hospital
      were maximal cyst excision and Roux-en-Y hepaticojejunostomy. Radical cyst
      excision was achieved in 93.5 % of patients with type I and 44.0 % of patients
      with type IV-A CCs. With an average follow-up of 48.23 +/- 12.30 months,
      recurrent cholangitis and biliary-enteric anastomotic stenosis occurred in 18
      (13.2 %) and 9 patients (6.6 %), respectively. Long-term biliary function was
      excellent or good in 83.8 % of patients. CONCLUSIONS: Radical cyst excision and
      Roux-en-Y hepaticojejunostomy provide good outcomes in patients with CCs.

PMID- 25373704
TI  - Can the risk of non-home discharge after resection of gastric adenocarcinoma be
      predicted: a seven-institution study of the US Gastric Cancer Collaborative.
AB  - BACKGROUND: There are no validated methods to preoperatively identify patients
      with increased risk of discharge to skilled nursing facilities following
      resection of gastric cancer. We sought to identify preoperative predictors of non
      home discharge to optimize transition of care to skilled nursing facility.
      METHODS: Patients who underwent resection of gastric cancer from 2000 to 2012
      from seven participating institutions of the US Gastric Cancer Collaborative were
      analyzed. Fisher's exact tests, Student t tests, and logistic regression analyses
      identified preoperative variables associated with non-home discharge. A
      prediction tool was created and validated through c-indices. Survival analysis
      was conducted according to the methods of Kaplan and Meier. RESULTS: Out of the
      918 patients identified, 93 (10 %) were discharged to nonhome location.
      Univariate analysis identified advancing age, American Society of Anesthesiology
      (ASA) score, hypertension, decreasing preoperative albumin, and lack of
      neoadjuvant chemotherapy as risk factors for non-home discharge (NHD).
      Multivariable analysis identified advanced age (odds ratio (OR) = 1.07, 95 %
      confidence interval (CI) = 1.04-1.10, p < 0.0001), depressed preoperative albumin
      (OR = 2.17, 95 % CI = 1.47-3.19, p = 0.0001), and total gastrectomy (OR = 2.56,
      95 % CI = 1.53-4.3, p = 0.0003) as risk factors for NHD. The c-index of the model
      and the validation population were 0.76 and 0.8, respectively. Additionally,
      there was an association of decreased overall survival in patients discharged to
      nonhome location (35.5 months, home discharge, vs 12 months, NHD, p < 0.0001).
      CONCLUSIONS: Older patients with compromised nutritional status have greater risk
      of NHD following resection of gastric cancer. The prediction tool can augment
      preoperative planning to optimize transition of care to skilled nursing facility.

PMID- 25373705
TI  - Effect of reoperation on long-term outcome of pT1b/T2 gallbladder carcinoma after
      initial laparoscopic cholecystectomy.
AB  - BACKGROUND: A small proportion of gallbladder carcinomas (GBC) are incidentally
      detected after laparoscopic cholecystectomy (LC). This study intended to analyze
      the effect of extended reoperation on the long-term outcome of patients with
      pT1b/T2 GBC who had initially undergone LC. METHODS: A cohort of 203 patients who
      underwent R0 resection and whose pathology was pT1b or pT2 GBC was divided into 3
      groups: open surgery (group I, n = 150), LC only (group II, n = 25), and initial
      LC and subsequent reoperation (group III, n = 28). RESULTS: Mean ages were 62.3
      +/- 9.6 years, 65.9 +/- 11.8 years, and 57.1 +/- 7.7 years in groups I, II, and
      III, respectively (p = 0.001). The numbers of pT1b and pT2 patients were 75 and
      75 in group I, 15 and 10 in group II, and 6 and 22 in group III, respectively.
      Residual tumors after LC were found in none of 6 pT1b patients and 5 of 22 pT2
      patients. Overall 5-year patient survival rate was 70.1 % for all-cause death and
      73.5 % for tumor recurrence-associated death (76.0 % in group I, 64.0 % in group
      II, and 63.0 % in group III [p = 0.607]; 84.4 % in pT1b group I, 68.8 % in pT1b
      group II, and 83.3 % in pT1b group III [p = 0.649]; 67.6 % in pT2 group I, 50 %
      in pT2 group II, and 61.9 % in pT2 group III [p = 0.895]). Concurrent bile duct
      resection in pT2 patients did not affect survival outcomes (p = 0.601).
      CONCLUSIONS: No definite survival benefit from reoperation was observed in
      patients with pT1b lesions. Residual tumor was found in 23 % of pT2 patients
      after reoperation, and the survival outcomes of these patients were comparable to
      those of the open surgery group. Therefore, reoperation for pT1b GBC following LC
      can be individually indicated because its indication remains unclear, but it
      should be highly recommended for pT2 GBC.

PMID- 25373707
TI  - Sexual partner mixing and differentials in consistent condom use among men who
      have sex with men in Maharashtra, India.
AB  - Sexual partner mixing among men who have sex with men (MSM), based on both gender
      and partnership status, is an understudied theme in India. Using data from Round
      2 of the Integrated Bio-behavioral Survey, this paper reports on gender and
      partnership status-based sexual mixing and levels of consistent condom use (CCU)
      among MSM in Maharashtra. A total of 689 MSM were sampled using probability-based
      sampling. Bivariate and regression analyses were carried out on condom use and
      partnership mixing. Over half (52%) of all MSM reported having only male partners
      while about one-third (34.5%) reported having partners of both gender. Over 70%
      of MSM engaged in sex with a mix of casual, regular, commercial and non
      commercial partners. MSM with only male partners reported lower CCU as compared
      to MSM with partners of both genders (47.3% and 62%, respectively, p = 0.11). CCU
      levels differed significantly by status of sex partner. Overall, MSM having 'men
      only' as partners and those with partners of mixed status have greater risk
      behaviour in terms of low CCU. HIV prevention interventions need to focus
      attention on men in 'exclusively male' sex partnerships as well as MSM with a mix
      of casual, regular and commercial partners.

PMID- 25373706
TI  - Current recommendations for surveillance and surgery of intraductal papillary
      mucinous neoplasms may overlook some patients with cancer.
AB  - BACKGROUND: The 2012 Sendai Criteria recommend that patients with 3 cm or larger
      branch duct intraductal papillary mucinous neoplasms (BD-IPMN) without any
      additional "worrisome features" or "high-risk stigmata" may undergo close
      observation. Furthermore, endoscopic ultrasound (EUS) is not recommended for BD
      IPMN <2 cm. These changes have generated concern among physicians treating
      patients with pancreatic diseases. The purposes of this study were to (i) apply
      the new Sendai guidelines to our institution's surgically resected BD-IPMN and
      (ii) reevaluate cyst size cutoffs in identifying patients with lesions harboring
      high-grade dysplasia or invasive cancer. METHODS: We retrospectively reviewed 150
      patients at a university medical center with preoperatively diagnosed and
      pathologically confirmed IPMNs. Sixty-six patients had BD-IPMN. Pathologic grade
      was dichotomized into low-grade (low or intermediate grade dysplasia) or high
      grade/invasive (high-grade dysplasia or invasive cancers). Fisher's exact test,
      chi-square test, student's t test, linear regression, and receiver operating
      characteristic (ROC) analyses were performed. RESULTS: The median BD-IPMN size on
      imaging was 2.4 cm (interquartile range 1.5-3.0). Fifty-one (77 %) low-grade and
      15 (23 %) high-grade/invasive BD-IPMN were identified. ROC analysis demonstrated
      that cyst size on preoperative imaging is a reasonable predictor of grade with an
      area under the curve of 0.691. Two-thirds of high-grade/invasive BD-IPMN were <3
      cm (n = 10). Compared to a cutoff of 3, 2 cm was associated with higher
      sensitivity (73.3 vs. 33.3 %) and negative predictive value (83.3 vs. 80 %, NPV)
      for high-grade/invasive BD-IPMN. Mural nodules on endoscopic ultrasound (EUS) or
      atypical cells on endoscopic ultrasound-fine needle aspiration (EUS-FNA) were
      identified in all cysts <2 and only 50 % of those <3 cm. Forty percent of cysts
      >3 cm were removed based on size alone. DISCUSSION/CONCLUSIONS: Our results
      suggest that "larger" size on noninvasive imaging can indicate high
      grade/invasive cysts, and EUS-FNA may help identify "smaller" cysts with high
      grade/invasive pathology.

PMID- 25373708
TI  - Laparoscopic metroplasty in bicornuate and didelphic uteri: feasibility and
      outcome.
AB  - PURPOSE: To report the outcomes of laparoscopic metroplasty in bicornuate and
      didelphic uteri. METHODS: This observational study includes 26 women with double
      uterine cavities (22 bicornuate and 4 didelphic uteri) with history of recurrent
      pregnancy loss undergoing laparoscopic metroplasty, second-look laparoscopy and
      hysteroscopy between 2008 and 2013 in University and Private hospital (Shiraz,
      Iran). The feasibility of laparoscopic metroplasty, appropriateness of the
      uterine cavity upon second-look laparoscopy, pregnancy outcome and live birth
      rate (within at least 12 month follow-up) were evaluated. RESULT(S): All patients
      had a unified and acceptable uterine cavity in second-look operation. Minimal
      pelvic adhesions in eight cases and subseptum of uterus in seven patients were
      detected which were removed by laparoscopy and resectoscopy, respectively. Out of
      14 patients who could be followed for one year for pregnancy occurrence 12
      patients had conception. Out of them nine term pregnancies with normal pregnancy
      and delivery outcomes were reported. These women delivered nine live neonates
      through the cesarean section. Three patients had pregnancy loss (2 early
      pregnancy losses and one with preterm delivery). Two patients decided to postpone
      conception due to personal reasons. CONCLUSION(S): Laparoscopic metroplasty by
      developing single uterine cavity with a suitable volume and minimal adhesion
      formation can be a substitute for laparotomy technique. However, more long-term
      studies should be done on larger sample size to confirm its positive effects on
      the pregnancy outcomes.

PMID- 25373709
TI  - High p-Smad2 expression in stromal fibroblasts predicts poor survival in patients
      with clinical stage I to IIIA non-small cell lung cancer.
AB  - BACKGROUND: Increasing evidence indicates that the TGFbeta/Smad signaling pathway
      plays a prominent role in tumor initiation, progression, and metastasis.
      Therefore, we investigate the expression of p-Smad2 in surgical resection
      specimens from non-small cell lung cancer, and evaluate the prognostic
      significance of p-Smad2 expression in stromal fibroblasts and cancer cells for
      patients with clinical stage I to IIIA non-small cell lung cancer. METHODS: The
      immunohistochemical expression of p-Smad2 was evaluated in 78 formalin-fixed
      paraffin-embedded surgical resection specimens from clinical stage I to IIIA non
      small cell lung cancer. Correlations between p-Smad2 expression and
      clinicopathologic characteristics were determined by Chi-square test. The
      prognostic significance of p-Smad2 expression in stromal fibroblasts and cancer
      cells with regard to overall survival was determined by Kaplan-Meier. RESULTS:
      There were 38.5% (30/78) and 92.3% (72/78) patients with high p-Smad2 expression
      in stromal fibroblasts and cancer cells, respectively. There was a positive
      correlation between the p-Smad2 expression level in stromal fibroblasts and the p
      Smad2 expression level in cancer cells (chi2=4.176, P=0.045). No significant
      correlation of p-Smad2 expression in stromal fibroblasts or cancer cells with any
      of clinicopathologic characteristics was found. The 3-year overall survival rates
      with low and high p-Smad2 expression in stromal fibroblasts were 53.7% and 37.7%,
      respectively (chi2=3.86, P=0.049). No significant association was found between
      low and high p-Smad2 expression in cancer cells with respect to overall survival,
      respectively (chi2=0.34, P=0.562). CONCLUSIONS: The results suggested that high p
      Smad2 expression in stromal fibroblasts predicted poor survival in patients with
      clinical stage I to IIIA non-small cell lung cancer.

PMID- 25373710
TI  - [Therapy of aortic valve stenosis].
AB  - Calcific aortic stenosis is the most frequent valve disorder in the western
      world. It is a degenerative and chronic progressive disease in the elderly with
      increasing prevalence due to the demographic development in the population. As
      there is no medical therapy, the only option in severe aortic stenosis is valve
      replacement. Echocardiography is the diagnostic tool to assess aortic stenosis
      severity and morphology of the valve. Aortic stenosis is severe if the valve area
      is <1.0 cm(2), valve index <0.6 cm(2)/m(2) body surface, mean gradient >40 mmHg,
      and peak velocity >4.0 m/s. The entity of low flow, low gradient aortic stenosis
      is complex, and diagnosis and therapy are still challenging. Asymptomatic
      patients have a good prognosis, but must be reevaluated on a regular basis for
      the onset of symptoms or signs of progression. If one of the classical symptoms
      dyspnea and fatigue, angina pectoris or syncope occurs prognosis worsens
      dramatically and valve replacement is indicated. Gold standard therapy for aortic
      stenosis is surgical valve replacement. For high-risk patients (older age and
      severe comorbidities), transcatheter aortic valve implantation (TAVI) is
      established as standard therapy.

PMID- 25373711
TI  - [Surgical treatment of obesity: status quo].
AB  - Obesity surgery has a proven beneficial effect on mortality for patients with a
      body mass index (BMI) >40 kg/m(2). For patients with type 2 diabetes and a BMI
      >35 kg/m(2), obesity surgery has also shown to improve metabolic control compared
      to conservative therapy. Treatment should be embedded in an interdisciplinary and
      experienced setting. Lifelong follow-up is mandatory. Due to the complexity of
      the patient collective, future treatment should focus on centers with a true
      interdisciplinary infrastructure.

PMID- 25373712
TI  - [New antibiotics prior to approval: is this the end of the innovative
      stagnation?].
AB  - BACKGROUND: Therapeutic efficacy and safety in infections due to multiresistant
      bacteria can be improved by the clinical development of new compounds and
      devising new derivatives of already useful antibiotics. Due to a striking global
      increase of multiresistant gram-negative and gram-positive organisms, new
      antibiotics are urgently needed. This paper provides a review of new
      pharmaceuticals which are already in clinical development, mainly in phase III
      trials. CONCLUSION: Each of these new trials increases the possibility of new
      antibiotics receiving approval.

PMID- 25373713
TI  - In situ modulation of cell behavior via smart dual-ligand surfaces.
AB  - Due to the highly complex nature of the extracellular matrix (ECM), the design
      and implementation of dynamic, stimuli-responsive surfaces that present well
      defined ligands and serve as model ECM substrates have been of tremendous
      interest to biomaterials, biosensor, and cell biology communities. Such tools
      provide strategies for identifying specific ligand-receptor interactions that
      induce vital biological consequences. Herein, we report a novel dual-ligand
      presenting surface methodology that modulates dynamic ECM properties to
      investigate various cell behaviors. Peptides PHSRN, cRGD, and KKKTTK, which mimic
      the cell- and heparan sulfate-binding domains of fibronectin, and carbohydrates
      Gal and Man were combined with cell adhesive RGD to survey possible synergistic
      or antagonist ligand effects on cell adhesion, spreading, growth, and migration.
      Soluble molecule and enzymatic inhibition assays were also performed, and the
      levels of focal adhesion kinase in cells subjected to different ligand
      combinations were quantified. A redox-responsive trigger was incorporated into
      this surface strategy to spontaneously release ligands in the presence of adhered
      cells, and cell spreading, growth, and migration responses were measured and
      compared. The identity and nature of the dual-ligand combination directly
      influenced cell behavior. 

PMID- 25373714
TI  - Living in hope and desperate for a miracle: NICU nurses perceptions of parental
      anguish.
AB  - The birth of an extremely premature baby is a tragedy, and it is only natural
      that the parents will rely on the spiritual and religious beliefs that guide the
      rest of their lives. At this difficult time, parents with strong religious
      beliefs will hope for divine intervention and pray for a miracle. This paper
      outlines the difficulties experienced by neonatal nurses when caring for an
      extremely premature baby whose parents hold on to hope and their belief in divine
      intervention and a miracle. Data were collected via a questionnaire to Australian
      neonatal nurses and semi-structured interviews with 24 neonatal nurses in NSW,
      Australia. A qualitative approach was used to analyse the data. The theme of
      "hoping for a miracle" was captured by two sub-themes "praying for a miracle" and
      "oscillating between hope and despair". For some families, the hope of divine
      intervention seemed all consuming, and the nurses were witness to the desperation
      and disappointment of families when a miracle was not forthcoming. 

PMID- 25373715
TI  - Differential microRNA expression profile comparison between epidermal stem cells
      and differentiated keratinocytes.
AB  - The aim of the current study was to analyze the differential microRNA (miRNA)
      expression profiles of human epidermal stem cells (ESCs) and differentiated
      keratinocytes. Enzyme digestion was used in combination with rapid adhesion to
      collagen IV to isolate primary human ESCs and differentiated keratinocytes, from
      which total RNA was extracted. Fluorescence labeling, microarray hybridization
      and differential expression analyses were performed. Reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) was performed to validate the
      reliability of the microarray results and predict the target genes of the
      differentially expressed miRNAs. A total of 25 miRNAs, including hsa-miR-197-5p,
      hsa-miR-125b-5p and hsa-miR-376a-3p, were upregulated, whereas 166 miRNAs,
      including hsa-miR-29b-3p, hsa-miR-203 and hsa-miR-34a-3p, were downregulated in
      the human ESCs compared with the expression in differentiated keratinocytes. RT
      qPCR results confirmed the upregulation of hsa-miR-197-5p and the downregulation
      of hsa-miR-29b-3p, which were consistent with the microarray results. miRNA
      target prediction indicated that the miRNA expression levels correlated with cell
      proliferation, differentiation, apoptosis and senescence. Expression levels of
      miRNAs significantly differed between human ESCs and differentiated
      keratinocytes. This finding may be attributed to their biological
      characteristics, such as proliferative behavior and differentiation abilities.

PMID- 25373716
TI  - Association between the mitochondrial DNA 4977 common deletion in the hair shaft
      and hearing loss in presbycusis.
AB  - The aim of the present study was to examine the role of the mitochondrial (mt)
      DNA common deletion (CD) 4977 (mtDNACD4977) in the hair shaft in patients with
      presbycusis. A total of 87 individuals with presbycusis and 95 normal-hearing
      controls were selected based on strict audiometric criteria. Nested polymerase
      chain reaction (PCR), sequencing and quantitative (q)PCR were used to examine the
      expression levels of mtDNACD4977 in the hair shaft in presbycusis. Nested PCR of
      the hair shaft demonstrated that 8/95 cases with normal hearing were found to be
      positive for mtDNACD4977, as compared with 59/87 cases in the presbycusis group.
      The mtDNACD4977 was positive in 22/43 cases with mild-to-moderate hearing loss,
      25/31 cases with moderate-to-severe, severe hearing loss, and 12/13 cases with
      profound deafness. Statistically significant differences in mtDNACD4977
      expression were identified among all of the groups (P<0.001). The sequencing and
      qPCR assays demonstrated a trend towards an increase in the mean CD level of
      mtDNACD4977 with a more severe hearing loss at 8 kHz (r=0.778, P<0.001) and all
      ranges of frequency (r=0.858, P<0.001). In conclusion, the present study
      demonstrates a correlation between mtDNACD4977 in the human hair shaft and the
      severity of hearing loss in presbycusis.

PMID- 25373717
TI  - Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced
      brain edema.
AB  - Connexin 43 (Cx43) and aquaporin-4 (AQP4) have important roles in the formation
      of glioma-induced brain edema; however, the association between these two factors
      in the development of edema has remained to be elucidated. In the present study,
      immunofluorescence and western blot analysis revealed that in a rat model of
      intracranial C6 glioma, Cx43 expression levels were low to undetectable and AQP4
      expression levels were low in glioma cells. Significantly higher Cx43 and AQP4
      levels were detected in the tissue surrounding the glioma. To further investigate
      the potential interaction between Cx43 and AQP4, normal glial cells and C6 glioma
      cells were cultured in hypotonic medium. Reverse transcription quantitative
      polymerase chain reaction indicated that AQP4 and Cx43 mRNA expression levels
      increased as a function of time in normal glial cells and C6 glioma cells in a
      hypotonic environment. However, the increase observed in normal glial cells was
      significantly lower than that observed in C6 glioma cells. Furthermore, AQP4
      expression levels changed prior to alterations in Cx43 expression. Following AQP4
      silencing in C6 cells, the increase in Cx43 expression was significantly
      attenuated (P<0.05). In normal cells, Cx43 silencing did not influence AQP4
      expression (P>0.05). Therefore, it was hypothesized that AQP4 and Cx43 had two
      distinct mechanisms underlying brain edema formation within and surrounding the
      glioma. Cx43 may be a downstream effector of AQP4. The elucidation of this
      pathway may aid in the development of drugs targeting the interaction between
      AQP4 and Cx43, providing novel therapeutic possibilities for glioma-induced brain
      edema. 

PMID- 25373718
TI  - Isolation of viable type I and II methanotrophs using cell-imprinted polyurethane
      thin films.
AB  - Studies on methanotrophs utilizing methane as sole source of carbon and energy
      are meaningful for governing global warming; although, the isolation of
      methanotrophs from nature is challenging. Here, surface imprinted polyurethane
      films were fabricated to selectively capture living methanotrophs from paddy
      soil. Two tracks of molecularly imprinted film based on polyurethane (PU-MIF1 and
      PU-MIF2) were imprinted using type I or II methanotrophs as template,
      respectively, and then reacted with polyethylene glycol, castor oil, and
      hexamethylene diisocyanate. Results demonstrated these PU-MIFs hold low water
      absorption rate and superior biocompatibility, which was highly demanded for
      maintaining cell viability. Superior selectivity and affinity of PU-MIFs toward
      their cognate methanotroph cells was observed by fluorescent microscopy. Atomic
      force microscopy revealed the adhesion force of PU-MIFs with its cognate cells
      was much stronger in comparison with noncognate ones. Using the as-prepared PU
      MIFs, within 30 min, methanotroph cells could be separated from rice paddy
      efficiently. Therefore, the PU-MIFs might be used as an efficient approach for
      cell sorting from environmental samples. 

PMID- 25373720
TI  - Selective Right Lower Lobe Isolation to Control CO2 in a Patient With Raised ICP
      Undergoing Craniotomy.

PMID- 25373719
TI  - Health effects of single motherhood on children in sub-Saharan Africa: a cross
      sectional study.
AB  - BACKGROUND: Although progress has been made toward reducing child morbidity and
      mortality globally, a large proportion of children in sub-Saharan Africa still
      die before age five and many suffer chronic malnutrition. This study investigated
      the influence of single motherhood on stunting and under-5 mortality in Cameroon,
      Nigeria and Democratic Republic of the Congo (DRC). Particular attention was paid
      to the influence of mother's economic resources, parental care and health
      behaviour on the difference in children's health in single and two-parent
      families. METHODS: Data were obtained from most recent Demographic and Health
      Surveys in Cameroon (2011), Nigeria (2008) and DRC (2007). The sample included
      women aged 15-49 years old and their under-5 children 11,748 in Cameroon, 28,100
      in Nigeria, and 8,999 in DRC. Logistic regression and Cox proportional hazard
      analysis were used to estimate stunting and under-5 mortality, respectively.
      RESULTS: The result showed that compared with children whose mothers were in
      union, children of single mothers who were not widows were more likely to be
      stunted (OR 1.79 p < 0.01 in Cameroon and 1.69 p < .01 in DRC). Economic
      resources and parental care significantly influenced the higher odds of stunting
      in single mother households in Cameroon and DRC. Relative to children of mothers
      in union, the risk of under-5 mortality in single mother families was higher in
      the three countries (HR 1.40 p < .05 in Cameroon, 1.27 p < 0.10 in DRC, 1.55 p <
      .01 in Nigeria). Economic resources, parental care and health behaviour accounted
      for the difference in Nigeria and Cameroon; in DRC, only economic resources had
      marginal influence. CONCLUSIONS: Single motherhood is a risk factor for
      children's nutritional status and chances of survival before age 5 years in sub
      Saharan Africa. To achieve improved reduction in children's exposure to stunting
      and under-5 mortality, there is the need for public health interventions targeted
      at single mother households in sub-Saharan Africa.

PMID- 25373723
TI  - Pre-procedure desmopressin acetate to reduce bleeding in renal failure: does it
      really work?
AB  - BACKGROUND: Desmopressin (DDAVP) is often used prior to procedures to minimize
      bleeding in patients with renal failure; however, there is little evidence to
      support this practice. The objectives of this study were to evaluate the practice
      of administration of DDAVP prior to procedures within our division and to
      determine the number of bleeding episodes for patients who received DDAVP
      compared to those who did not. METHODS: Hospital records of patients who
      underwent renal biopsy or central line placement between April 2006 and March
      2008 were reviewed. Patients with glomerular filtration rate (GFR) <60
      ml/min/1.73 m(2) were identified and subcategorized into three groups: group A
      GFR <15 ml/min/1.73 m(2), group B GFR 15-29 ml/min/1.73 m(2), and group C GFR 30
      60 ml/min/1.73 m(2). The number of bleeding events was noted in each group.
      RESULTS: No significant difference was found in the number of bleeding events
      between those who received and did not receive DDAVP overall and in each GFR
      group. A possible trend towards the benefit with treatment in group A was
      observed. CONCLUSION: There was no significant reduction in bleeding for those
      who received DDAVP which questions the validity of this practice. Patients with
      GFR <15 ml/min/1.73 m(2) may possibly derive benefit.

PMID- 25373725
TI  - Effective AC needleless and collectorless electrospinning for yarn production.
AB  - Nanofibrous materials are essential components for a wide range of applications,
      particularly in the fields of medicine and material engineering. These include
      protective materials, sensors, cosmetics, hygiene, filtration and energy storage.
      The most widely used and researched technology in these fields is
      electrospinning. This method for producing fibers yields highly promising results
      thanks to its versatility and simplicity. Electrospinning is employed in multiple
      forms, among which needle and needleless direct current (DC) variants are the
      most distinctive. The former is based on the generation of just one single jet
      from a nozzle; hence this fabrication process is not very productive. The latter
      uses the destabilization of free liquid surfaces by means of an electric field,
      which enhances the throughput since it produces numerous jets, emitted from the
      surfaces of rollers, spheres, strings and spirals. However, although some
      progress in total producibility has been achieved, the efficiency of the DC
      method still remains relatively low. A further drawback of DC electrospinning is
      that both variants need a collector, which makes it difficult to combine DC
      electrospinning easily with other technologies due to the presence of the high
      field strength within the entire spinning zone. This paper describes our
      experiments with AC electrospinning. We show that alternating current (AC)
      electrospinning based on a needleless spinning-electrode provides a highly
      productive smoke-like aerogel composed of nanofibers. This aerogel rises rapidly
      from the electrode like a thin plume of smoke, without any need for a collector.
      Our work shows that AC needleless electrospinning gains its efficiency and
      collector-less feature thanks to the creation of a perpetually charge-changing
      virtual counter-electrode composed of the nanofibers emitted. High-speed camera
      recordings demonstrate the formation mechanism of the nanofibrous plume, which is
      wafted by an electric wind. This wind's velocity field is experimentally
      investigated. One potential use of AC needleless electrospinning is demonstrated
      here by spinning it into a yarn. 

PMID- 25373724
TI  - Pain reduction in myofascial pain syndrome by anodal transcranial direct current
      stimulation combined with standard treatment: a randomized controlled study.
AB  - BACKGROUND: Myofascial pain syndrome (MPS) in the shoulder is among the most
      prevalent pain problems in the middle-aged population worldwide. Evidence
      suggests that peripheral and central sensitization may play an important role in
      the development and maintenance of shoulder MPS. Given previous research
      supporting the potential efficacy of anodal transcranial direct current
      stimulation (tDCS) for modulating pain-related brain activity in individuals with
      refractory central pain, we hypothesized that anodal tDCS when applied over the
      primary motor cortex (M1) combined with standard treatment will be more effective
      for reducing pain in patients with MPS than standard treatment alone. METHODS AND
      MATERIALS: Study participants were randomized to receive either (1) standard
      treatment with 5 consecutive days of 1 mA anodal tDCS over M1 for 20 minutes; or
      (2) standard treatment plus sham tDCS. Measures of pain intensity, shoulder
      passive range of motion (PROM), analgesic medication use, and self-reported
      physical functioning were administered before treatment and again at
      posttreatment and 1-, 2-, 3-, and 4-week follow-up. RESULTS: Thirty-one patients
      with MPS were enrolled. Participants assigned to the active tDCS condition
      reported significantly more pretreatment to posttreatment reductions in pain
      intensity that were maintained at 1-week posttreatment, and significant
      improvement in shoulder adduction PROM at 1-week follow-up than participants
      assigned to the sham tDCS condition. CONCLUSIONS: Five consecutive days of anodal
      tDCS over M1 combined with standard treatment appears to reduce pain intensity
      and may improve PROM, faster than standard treatment alone. Further tests on the
      efficacy and duration of effects of tDCS in the treatment of MPS are warranted.

PMID- 25373726
TI  - Cervical cancer-associated promoter polymorphism affects akna expression levels.
AB  - Cervical cancer (CC) is responsible for >260,000 deaths worldwide each year.
      Efforts are being focused on identifying genetic susceptibility factors,
      especially in genes related to the immune response. Akna has been proposed to be
      one of them, but data regarding its functional role in the disease is scarce.
      Supporting the notion of akna as a CC susceptibility gene, we found two
      polymorphisms associated with squamous intraepithelial lesion (SIL) and CC;
      moreover, we identified an association between high akna expression levels and CC
      and SIL, but its direction differs in each disease stage. To show the potential
      existence of a cis-acting polymorphism, we assessed akna allelic expression
      imbalance for the alleles of the -1372C>A polymorphism. We found that, regardless
      of the study group, the number of transcripts derived from the A allele was
      significantly higher than those from the C allele. Our results support the
      hypothesis that akna is a CC susceptibility genetic factor and suggest that akna
      transcriptional regulation has a role in the disease. We anticipate our study to
      be a starting point for in vitro evaluation of akna transcriptional regulation
      and for the identification of transcription factors and cis-elements regulating
      AKNA function that are involved in carcinogenesis.

PMID- 25373727
TI  - Associations of HLA class I alleles in Japanese patients with Crohn's disease.
AB  - Previous studies have suggested that the human leukocyte antigen (HLA) is
      involved in the etiology of Crohn's disease (CD); however, few reports are
      available on the association between HLA class I antigens and CD in Japan. In
      this study, we performed association analysis of HLA class I antigens in CD using
      208 Japanese patients and 384 healthy controls. We identified novel positive
      associations between CD and HLA-A*02:01 (odds ratio (OR)=1.64, P=0.016) and HLA
      A*02:07 (OR=2.31, P=0.0067) and confirmed previously reported positive
      associations between CD and HLA-Cw*14:02 (OR=2.18, P=0.0021) and HLA-B*51:01
      (OR=1.70, P=0.033). We also identified novel negative associations between CD and
      HLA-A*24:02 (OR=0.60, P=0.0047) and HLA-B*07:02 (OR=0.38, P=0.0041). Although the
      associations were not significant after full Bonferroni correction, we suggested
      that HLA class I genes have dual functions, susceptibility and resistance in
      controlling the development of CD. 

PMID- 25373728
TI  - Evidence of histidine and aspartic acid phosphorylation in human prostate cancer
      cells.
AB  - We have developed a method to identify previously undetected histidine and
      aspartic acid phosphorylations in a human prostate cancer progression model. A
      phosphoproteome of our cell line model is presented, with correlation of modified
      protein expression between the three states of cancer: non-tumorigenic,
      tumorigenic, and metastatic cells. With the described interaction proteins
      potentially phosphorylated by NM23-H1, cellular responses to motility and
      conformational change stimuli would be achievable. We detect 20 novel histidine
      phosphorylated (pHis) and 80 novel aspartic acid-phosphorylated (pAsp) proteins
      with diverse functions, such as metabolism, protein folding, and motility. Our
      data indicate that pHis and pAsp are much more prevalent than previously
      appreciated and may provide insight into the role of NM23-H1 and signaling events
      that are critical for metastasis. Using the described method for detecting
      histidine and aspartic acid phosphorylations and our prostate cancer progression
      cell system, the potential function of NM23-H1 in suppressing metastasis with a
      two-component regulation system is discussed. 

PMID- 25373729
TI  - Effect of sevoflurane concentration on visual evoked potentials with pattern
      stimulation in dogs.
AB  - The purpose of this study was to investigate the effects of sevoflurane
      concentration on canine visual evoked potentials with pattern stimulation (P
      VEPs). Six clinically normal laboratory-beagle dogs were used. The minimum
      alveolar concentration (MAC) of sevoflurane was detected from all subjects by
      tail clamp method. The refractive power of the right eyes of all subjects was
      corrected to -2 diopters after skiascopy. For P-VEP recording, the recording and
      reference electrode were positioned at inion and nasion, respectively, and the
      earth electrode was positioned on the inner surface. To grasp the state of CNS
      suppression objectively, the bispectral index (BIS) value was used. The stimulus
      pattern size and distance for VEP recording were constant, 50.3 arc-min and 50
      cm, respectively. P-VEPs and BIS values were recorded under sevoflurane in oxygen
      inhalational anesthesia at 0.5, 1.0, 1.5, 2.0, 2.5 and 2.75 sevoflurane MAC. For
      analysis of P-VEP, the P100 implicit time and N75-P100 amplitude were estimated.
      P-VEPs were detected at 0.5 to 1.5 MAC in all dogs, and disappeared at 2.0 MAC in
      four dogs and at 2.5 and 2.75 MAC in one dog each. The BIS value decreased with
      increasing sevoflurane MAC, and burst suppression began to appear from 1.5 MAC.
      There was no significant change in P100 implicit time and N75-P100 amplitude with
      any concentration of sevoflurane. At concentrations around 1.5 MAC, which are
      used routinely to immobilize dogs, sevoflurane showed no effect on P-VEP. 

PMID- 25373731
TI  - Silver(I) and thallium(I) cations as unsupported bridges between two metal bases.
AB  - Stirring Lewis-basic transition metal complexes with the salts M[BAr(Cl)4] (M =
      Ag, Tl; Ar(Cl) = 3,5-C6H3Cl2) resulted in the formation of diplatinum complexes
      [{(Cy3P)2Pt}2(MU-Ag)][BAr(Cl)4] (3) and [{(Cy3P)2Pt}2(MU-Tl)][BAr(Cl)4] (4) and
      the diiron compound [{(OC)3(Me3P)2Fe}2(MU-Ag)] (5) featuring bridging,
      unsupported metal cations. Their properties were investigated by multinuclear NMR
      spectroscopy, as well as X-ray diffraction and infrared measurements.

PMID- 25373730
TI  - Reduced-toxicity myeloablative conditioning consisting of 8-Gy total body
      irradiation, cyclophosphamide and fludarabine for pediatric hematological
      malignancies.
AB  - Conventional myeloablative conditioning (MAC) regimens often cause severe regimen
      related toxicity (RRT). Furthermore, many patients suffer from poor quality of
      life in accordance with the increase in long-term survivors. We therefore devised
      a reduced-toxicity myeloablative conditioning (RTMAC) regimen consisting of 8-Gy
      total body irradiation (TBI), fludarabine (FLU) and cyclophosphamide (CY) for
      pediatric hematological malignancies. A retrospective single-center analysis was
      performed on patients with leukemia or myelodysplastic syndrome (MDS), aged <=20
      years, who had received an 8-Gy TBI/FLU/CY RTMAC regimen followed by allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). Thirty-one patients
      underwent first allo-HSCT after an RTMAC regimen. The diagnoses were acute
      lymphoblastic leukemia (n = 11), acute myeloid leukemia (n = 13), MDS (n = 4),
      juvenile myelomonocytic leukemia (n = 1) and acute leukemias of ambiguous lineage
      (n = 2). While 3 patients showed early hematological relapse, the remaining 28
      patients achieved engraftments. None of the patients developed grade 4 or 5
      toxicities during the study period. The 5-year overall survival and relapse-free
      survival were 80% [95% confidence interval: CI, 61-91%] and 71% [95% CI, 52-84%],
      respectively. Our RTMAC regimen would be less toxic and offers a high probability
      of survival for children with hematological malignancies. 

PMID- 25373732
TI  - Lophine derivatives as activators in peroxyoxalate chemiluminescence.
AB  - Lophine and four of its derivatives were used as activators (ACTs) of the
      chemiluminescent peroxyoxalate (PO) reaction of bis(2,4,6-trichlorophenyl)oxalate
      with H2O2, catalysed by imidazole. Kinetic emission assays have shown that with
      the tested compounds the reaction mechanism, regarding the formation of the high
      energy intermediate (HEI) of the PO reaction, occurs as previously seen for
      commonly used ACTs. A bimolecular interaction of the compounds with the HEI leads
      to chemiexcitation through the chemically initiated electron exchange
      luminescence (CIEEL) mechanism, as confirmed by a linear free-energy correlation
      between the relative catalytic rate constants and the oxidation potentials of the
      compounds. The yields of excited state formation and light emission, in the range
      of 10(-2)-10(-3) E mol(-1), are comparable to the ones seen with commonly used
      ACTs. A Hammett plot with rho = -0.90 indicates the buildup of a partial positive
      charge on the transition step of the catalytic process, consistent with the
      formation of a radical cation of the ACT, being an additional validation of the
      CIEEL mechanism in this system. 

PMID- 25373733
TI  - Targeting hypoxia-inducible factor-1alpha (HIF-1alpha) in combination with
      antiangiogenic therapy: a phase I trial of bortezomib plus bevacizumab.
AB  - PURPOSE: We hypothesized that bortezomib, an agent that suppresses HIF-1alpha
      transcriptional activity, when combined with bevacizumab, would obviate the HIF
      1alpha resistance pathway. The objectives of this phase I trial were to assess
      safety and biological activity of this combination. EXPERIMENTAL DESIGN: Patients
      with advanced, refractory malignancies were eligible. Patients received
      bevacizumab and bortezomib (3-week cycle) with dose expansions permitted if
      responses were seen and for assessing correlates. Pharmacodynamic assessment
      included plasma VEGF, VEGFR2, 20S proteasome inhibition, dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI), and HIF-1alpha tumor expression.
      RESULTS: Ninety-one patients were treated (median=6 prior treatments). The FDA
      approved doses of both drugs were safely reached, and the recommended phase 2
      dose (RP2D) is bevacizumab 15 mg/kg with bortezomib 1.3 mg/m(2). Four patients
      attained partial response (PR) and seven patients achieved stable disease (SD) >=
      6 months (Total SD >= 6 months/PR=11 (12%)). The most common drug-related
      toxicities included thrombocytopenia (23%) and fatigue (19%). DCE-MRI analysis
      demonstrated no dose-dependent decreases in K(trans) although analysis was
      limited by small sample size (N=12). CONCLUSION: Combination bevacizumab and
      bortezomib is well-tolerated and has demonstrated clinical activity in patients
      with previously treated advanced malignancy. Pharmacodynamic assessment suggests
      that inhibition of angiogenic activity was achieved.

PMID- 25373734
TI  - Angiostatic, tumor inflammatory and anti-tumor effects of CXCL4(47-70) and
      CXCL4L1(47-70) in an EGF-dependent breast cancer model.
AB  - CXCL4 and CXCL4L1, platelet-derived CXC chemokines, and their carboxy-terminal
      peptides CXCL4(47-70) and CXCL4L1(47-70) previously displayed angiostatic and
      anti-tumoral activity in a melanoma model. Here, we found CXCL4(47-70) and
      CXCL4L1(47-70) to inhibit lymphatic endothelial cell proliferation in vitro.
      Furthermore, the angiostatic potential of CXCL4(47-70) and CXCL4L1(47-70) was
      tested against different angiogenic stimuli (FGF1, FGF2, FGF8, EGF and VEGF).
      Besides reducing FGF2-induced vascular endothelial cell growth, CXCL4(47-70) and
      CXCL4L1(47-70) efficiently counteracted EGF. Consequently, we considered their
      anti-tumoral potential in EGF-dependent MDA-MB-231 breast tumors. In tumor
      bearing mice, CXCL4(47-70) reduced tumor growth better than CXCL4L1(47-70). In
      CXCL4(47-70)-treated tumors significantly more intratumoral monocytes/macrophages
      and dendritic cells were present and higher expression levels of CCL5 and IFN-
      gamma were detected by qPCR on tumor lysates. Because neither peptide was able to
      specifically bind CXCR3A or CXCR3B, differential glycosaminoglycan binding and
      direct interaction with cytokines (EGF and CCL5) might explain any differences in
      anti-tumoral effects. Notably, CCL5-induced monocyte chemotaxis in vitro was
      increased by addition of CXCL4(47-70) or CXCL4L1(47-70). Finally, CXCL4(47-70)
      and CXCL4L1(47-70) inhibited proliferation of MDA-MB-231 cells. Our results
      suggest a tumor type-dependent responsiveness to either CXCL4(47-70) or
      CXCL4L1(47-70) treatment, defined by anti-proliferative, angiostatic and
      inflammatory actions, and substantiate their therapeutic potential.

PMID- 25373735
TI  - The role of systemic chemotherapy and multidisciplinary management in improving
      the overall survival of patients with metastatic squamous cell carcinoma of the
      anal canal.
AB  - Metastatic squamous cell carcinoma (SCCA) of the anal canal is a rare malignancy
      for which no standard treatment algorithm exists. To determine the best approach,
      all patients diagnosed with metastatic SCCA of the anal canal treated at a single
      institution were evaluated for choice of chemotherapy and treatment outcome. A
      retrospective study from January 2000 to May 2012 was conducted. Electronic
      medical records were reviewed for diagnosis of metastatic SCCA of the anal canal.
      All patients were treatment naive for metastatic disease and completed all
      radiographic imaging at our institution. The purpose of this study was to
      evaluate outcomes among patients who received systemic chemotherapy and if
      appropriate were referred for multidisciplinary intervention (e.g., surgery,
      radiofrequency ablation, etc.). Seventy-seven patients fulfilled eligibility
      criteria. Forty-two patients (55%) received 5-fluorouracil (5-FU) + cisplatin
      (PF); 24 patients (31%) received carboplatin + paclitaxel (CP); 11 patients (14%)
      received an alternative regimen. After a median follow-up of 42 months, the
      median progression-free survival (PFS) for all patients was 7 months; the median
      overall survival (OS) was 22 months. Thirty-three patients (43%) underwent
      multidisciplinary management for metastatic disease resulting in a median PFS of
      16 months (95% CI: 9.2 -22.8) and median OS of 53 months (95% CI: 28.3 - 77.6).
      Systemic chemotherapy provides durable survival for patients with surgically
      unresectable metastatic SCCA of the anal canal. Multidisciplinary management for
      select patients with metastatic disease effectively improves survival and should
      be considered whenever possible.

PMID- 25373736
TI  - Mastl kinase, a promising therapeutic target, promotes cancer recurrence.
AB  - Mastl kinase promotes mitotic progression and cell cycle reentry after DNA
      damage. We report here that Mastl is frequently upregulated in various types of
      cancer. This upregulation was correlated with cancer progression in breast and
      oral cancer, poor patient survival in breast cancer, and tumor recurrence in head
      and neck squamous cell carcinoma. We further investigated the role of Mastl in
      tumor resistance using cell lines derived from the initial and recurrent tumors
      of the same head and neck squamous cell carcinoma patients. Ectopic expression of
      Mastl in the initial tumor cells strongly promoted cell proliferation in the
      presence of cisplatin by attenuating DNA damage signaling and cell death. Mastl
      knockdown in recurrent tumor cells re-sensitized their response to cancer therapy
      in vitro and in vivo. Finally, Mastl targeting specifically potentiated cancer
      cells to cell death in chemotherapy while sparing normal cells. Thus, this study
      revealed that Mastl upregulation is involved in cancer progression and tumor
      recurrence after initial cancer therapy, and validated Mastl as a promising
      target to increase the therapeutic window. 

PMID- 25373737
TI  - Suppressor of fused (Sufu) represses Gli1 transcription and nuclear accumulation,
      inhibits glioma cell proliferation, invasion and vasculogenic mimicry, improving
      glioma chemo-sensitivity and prognosis.
AB  - Glioblastoma are highly aggressive brain tumors with poor prognosis. While
      various dysregulation of signaling pathways in gliomas have been described, the
      identification of biomarkers and therapy targets remains an important task for
      novel diagnostic and therapeutic approaches. Here we described that the
      Suppressor of fused (also known as Sufu) is significantly down-regulated in high
      grade gliomas, correlating with a poor prognosis. We demonstrated that ectopic
      expression of Sufu inhibited cell proliferation, invasion and vasculogenic
      mimicry. In addition, overexpression of Sufu reduced Gli reporter gene
      transcription activity and prevented Gli1 nuclear accumulation, whereas knockdown
      of Sufu reversed these effects. Furthermore, overexpressed Sufu sensitized
      glioblastoma to Temozolomide and Cyclopamine. Thus, Sufu is potential tumor
      suppressor and therapeutic target in glioblastoma. 

PMID- 25373738
TI  - ZNF282 (Zinc finger protein 282), a novel E2F1 co-activator, promotes esophageal
      squamous cell carcinoma.
AB  - Zinc finger protein 282 (ZNF282) is a newly identified transcription factor and
      little is known about its expression and function. Originally, ZNF282 is known to
      bind U5RE (U5 repressive element) of HLTV-1 (human T cell leukemia virus type 1)
      with a repressive effect. Recently we reported that ZNF282 functions as an
      estrogen receptor co-activator and plays an essential role in breast
      tumorigenesis. Although these results suggest the possible role of ZNF282 in
      cancers, clinical significance and function of ZNF282 are completely unknown in
      most of cancers. Here we found that ZNF282 was frequently overexpressed in
      esophageal squamous cell carcinoma (ESCC) (n=165) compared with normal esophageal
      epithelium and its overexpression was correlated with adverse clinical outcome.
      Multivariate survival analysis indicated that ZNF282 expression was an
      independent prognostic predictor for poor survival in ESCC (HR: 2.56 (95% CI 1.54
      4.26), p<0.001). In addition, depletion of ZNF282 inhibited the cell cycle
      progression, migration, and invasion of ESCC cells and reduced the tumorigenicity
      of ESCC xenograft in nude mouse. We further showed that ZNF282 is required for
      E2F1-mediated gene expression in ESCC cells. Thus, ZNF282 is E2F1 co-activator
      involved in ESCC and elevated expression of ZNF282 is an independent adverse
      prognostic factor in ESCC. 

PMID- 25373739
TI  - Leaf nitrogen and phosphorus of temperate desert plants in response to climate
      and soil nutrient availability.
AB  - In desert ecosystems, plant growth and nutrient uptake are restricted by
      availability of soil nitrogen (N) and phosphorus (P). The effects of both climate
      and soil nutrient conditions on N and P concentrations among desert plant life
      forms (annual, perennial and shrub) remain unclear. We assessed leaf N and P
      levels of 54 desert plants and measured the corresponding soil N and P in shallow
      (0-10 cm), middle (10-40 cm) and deep soil layers (40-100 cm), at 52 sites in a
      temperate desert of northwest China. Leaf P and N:P ratios varied markedly among
      life forms. Leaf P was higher in annuals and perennials than in shrubs. Leaf N
      and P showed a negative relationship with mean annual temperature (MAT) and no
      relationship with mean annual precipitation (MAP), but a positive relationship
      with soil P. Leaf P of shrubs was positively related to soil P in the deep soil.
      Our study indicated that leaf N and P across the three life forms were influenced
      by soil P. Deep-rooted plants may enhance the availability of P in the surface
      soil facilitating growth of shallow-rooted life forms in this N and P limited
      system, but further research is warranted on this aspect.

PMID- 25373741
TI  - Effective chronic low back pain and knee pain treatment with acupuncture in
      geriatric patients.
AB  - BACKGROUND: The most common disease of the older age group in Turkey is
      degenerative articular disease and pain associated with the disease. Analgesics
      and physical therapy are preferred treatment for geriatric chronic pain but
      suffering from multiple medical and nutritional problems in old ages can limit
      treatment options with analgesics due to an increased risk of adverse effects and
      drug interactions. OBJECTIVES: We aim to show the effect of acupuncture on back
      pain and knee-pain treatment of elderly people. METHODS: The study includes 34
      patients, 24 female and 8 male. The mean age was 69.0417 +/- 8.95 years for
      females and 73.12 +/- 8.95.24 years for males. Every two days for a total of 10
      sessions acupuncture treatment to Yintang, Ht 7 (Shenmen), LI 4 (Hegu), Ki 3
      (Taixi) and Ki 6 were found to significantly reduce pain scores of patients.
      RESULTS: Mean back pain scores (8.8696 +/- 1.546) and mean knee pain scores
      (9.1304 +/- 1.4239) of patients were reduced significantly to 2.1739 +/- 1.466
      and 1.455 +/- 0.7; p< 0.001 respectively after the acupuncture treatment.
      CONCLUSION: These are important results as they give rationale to use acupuncture
      treatment widely in chronic low back pain and knee pain in the geriatric group of
      patients to reduce the side effects of polypharmacy in elderly.

PMID- 25373740
TI  - How age and sex affect the erythrocyte sedimentation rate and C-reactive protein
      in early rheumatoid arthritis.
AB  - BACKGROUND: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
      are two commonly used measures of inflammation in rheumatoid arthritis (RA). As
      current RA treatment guidelines strongly emphasize early and aggressive treatment
      aiming at fast remission, optimal measurement of inflammation becomes
      increasingly important. Dependencies with age, sex, and body mass index have been
      shown for both inflammatory markers, yet it remains unclear which inflammatory
      marker is affected least by these effects in patients with early RA. METHODS:
      Baseline data from 589 patients from the DREAM registry were used for analyses.
      Associations between the inflammatory markers and age, sex, and BMI were
      evaluated first using univariate linear regression analyses. Next, it was tested
      whether these associations were independent of a patient's current disease
      activity as well as of each other using multiple linear regression analyses with
      backward elimination. The strengths of the associations were compared using
      standardized beta (beta) coefficients. The multivariate analyses were repeated
      after 1 year. RESULTS: At baseline, both the ESR and CRP were univariately
      associated with age, sex, and BMI, although the association with BMI disappeared
      in multivariate analyses. ESR and CRP levels significantly increased with age
      (beta-ESR=0.017, p<0.001 and beta-CRP=0.009, p=0.006), independent of the number
      of tender and swollen joints, general health, and sex. For each decade of aging,
      ESR and CRP levels became 1.19 and 1.09 times higher, respectively. Furthermore,
      women demonstrated average ESR levels that were 1.22 times higher than that of
      men (beta=0.198, p=0.007), whereas men had 1.20 times higher CRP levels (beta=
      0.182, p=0.048). Effects were strongest on the ESR. BMI became significantly
      associated with both inflammatory markers after 1 year, showing higher levels
      with increasing weight. Age continued to be significantly associated, whereas sex
      remained only associated with the ESR level. CONCLUSIONS: Age and sex are
      independently associated with the levels of both acute phase reactants in early
      RA, emphasizing the need to take these external factors into account when
      interpreting disease activity measures. BMI appears to become more relevant at
      later stages of the disease.

PMID- 25373742
TI  - Effect of trunk muscles training using a star excursion balance test grid on
      strength, endurance and disability in persons with chronic low back pain.
AB  - BACKGROUND AND OBJECTIVES: Though core muscles strengthening using upper limbs in
      various positions and lower limbs in lying have been studied previously in
      patients with chronic low back pain (CLBP), no study has specifically looked in
      to the effects of a training program that requires prior motor planning in
      standing (functional position). The objective of this study was to evaluate the
      effectiveness of star excursion balance test (SEBT) grid training in improving
      the outcomes in patients with CLBP. MATERIALS AND METHOD: Sixty patients with
      mechanical CLBP who fulfilled our criteria were randomized in to two groups;
      experimental group received physical diagnostic specific interventions, core
      muscles strengthening and muscles training using the SEBT grid. The participants
      in control group received stationary cycling instead of SEBT grid training and
      the other interventions were uniform. The duration of study was 4 weeks. The
      dependent variables were analyzed using repeated measures 2 * 3 ANOVA. RESULTS:
      At the end of study, both the groups showed a significant reduction in disability
      and improvement in strength and endurance (p< 0.05). Post-hoc analysis showed
      that SEBT grid training was better than conventional exercises. Follow-up at 16
      weeks revealed a statistically insignificant loss in strength and endurance in
      control group patients. This reduction was not associated with an increase in
      disability score. The experimental group patients continued showing improvement.
      CONCLUSION: The results of our study show that core muscles strengthening using a
      SEBT grid are more effective than conventional programs. We hypothesize SEBT
      training to have a significant role in skill learning. We recommend SEBT grid
      training to be incorporated in the treatment planning of persons with CLBP.

PMID- 25373743
TI  - Emerging pollutants in the Esmeraldas watershed in Ecuador: discharge and
      attenuation of emerging organic pollutants along the San Pedro-Guayllabamba
      Esmeraldas rivers.
AB  - Water quality characteristics and emerging organic pollutants were sampled along
      the San Pedro-Guayllabamba-Esmeraldas River and its main water pollution streams
      in the summer of 2013. The annual flow rate of the stream is 22 000 Mm(3) y(-1)
      and it collects the wastewater of Quito-Ecuador in the Andes and supplies
      drinking water to the city of Esmeraldas near the Pacific Ocean. The most
      persistent emerging pollutants were carbamazepine and acesulfame, which were
      found to be stable along the San Pedro-Guayllabamba-Esmeraldas River, whereas the
      concentration of most other organic emerging pollutants, such as caffeine,
      sulfamethoxazole, venlafaxine, O-desmethylvenlafaxine, and steroidal estrogens,
      was degraded to a large extent along the 300 km flow. The mass rate of the sum of
      cocaine and benzoylecgonine, its metabolite, was increased along the stream,
      which may be attributed to coca plantations and wild coca trees. This raises the
      possibility of using river monitoring as an indirect way to learn about changes
      in coca plantations in their watersheds. Several organic emerging pollutants,
      such as venlafaxine, carbamazepine, sulphamethoxazole, and benzoylecgonine,
      survived even the filtration treatment at the Esmeraldas drinking water system,
      though all except for benzoylecgonine are found below 20 ng L(-1), and are
      therefore not likely to cause adverse health effects. The research provides a way
      to compare drug consumption in a major Latin American city (Quito) and shows that
      the consumption of most sampled drugs (carbamazepine, venlafaxine, O
      desmethylvenlafaxine, sulphamethoxazole, ethinylestradiol) was below their
      average consumption level in Europe, Israel, and North America. 

PMID- 25373744
TI  - The surgical management of male epispadias in the new millennium.
AB  - Male epispadias is a rare and challenging urologic condition. As part of the
      epispadias-exstrophy complex of genitourinary anomalies, it covers a broad
      spectrum with the mildest forms being the rarest. The anatomic classification
      into glanular, penile, and penopubic is based on the location of the urethral
      meatus. However, this classification fails to include some of the suprapubic
      malformations that may be present such as pubic diastasis, bladder neck
      abnormalities, and vesicoureteral reflux. Careful preoperative evaluation should
      allow the identification of these anomalies and will help achieve the goals of
      surgical reconstruction. These goals include cosmetic and functional
      reconstruction of the penis and urethra as well as, when needed, creation of a
      continence mechanism that will allow for normal bladder function, storage, and
      evacuation of urine. This review will focus on: 1) the preoperative evaluation
      and management of male patients with epispadias and 2) surgical management based
      on the anatomic classification. 

PMID- 25373745
TI  - Advances in plant genotyping: where the future will take us.
AB  - Genetic diversity between individuals can be tracked and monitored using a range
      of molecular markers. These markers can detect variation ranging in scale from a
      single base pair up to duplications and translocations of entire chromosomal
      regions. The genotyping of individuals allows the detection of this variation and
      it has been successfully applied in plant science for many years. The increasing
      amounts of sequence data able to be generated using next-generation sequencing
      (NGS) technologies have produced a vast expansion in the rate of discovery of
      polymorphisms, with single nucleotide polymorphisms (SNPs) predominating as the
      marker of choice. This increase in polymorphic marker resources through efficient
      discovery, coupled with the utility of SNPs, has enabled the shift to high
      throughput genotyping assays and these methods are reviewed and discussed here,
      alongside the recent innovations allowing increased throughput. 

PMID- 25373746
TI  - Molecular marker applications in plants.
AB  - Individuals within a population of a sexually reproducing species will have some
      degree of heritable genomic variation caused by mutations, insertion/deletions
      (INDELS), inversions, duplications, and translocations. Such variation can be
      detected and screened using molecular, or genetic, markers. By definition,
      molecular markers are genetic loci that can be easily tracked and quantified in a
      population and may be associated with a particular gene or trait of interest.
      This chapter will review the current major applications of molecular markers in
      plants. 

PMID- 25373747
TI  - Bioinformatics: identification of markers from next-generation sequence data.
AB  - With the advent of sequencing technology, next-generation sequencing (NGS)
      technology has dramatically revolutionized plant genomics. NGS technology
      combined with new software tools enables the discovery, validation, and
      assessment of genetic markers on a large scale. Among different markers systems,
      simple sequence repeats (SSRs) and Single nucleotide polymorphisms (SNPs) are the
      markers of choice for genetics and plant breeding. SSR markers have been a choice
      for large-scale characterization of germplasm collections, construction of
      genetic maps, and QTL identification. Similarly, SNPs are the most abundant
      genetic variations with higher frequencies throughout the genome of plant
      species. This chapter discusses various tools available for genome assembly and
      widely focuses on SSR and SNP marker discovery. 

PMID- 25373748
TI  - Molecular marker databases.
AB  - The detection and analysis of genetic variation plays an important role in plant
      breeding and this role is increasing with the continued development of genome
      sequencing technologies. Molecular genetic markers are important tools to
      characterize genetic variation and assist with genomic breeding. Processing and
      storing the growing abundance of molecular marker data being produced requires
      the development of specific bioinformatics tools and advanced databases.
      Molecular marker databases range from species specific through to organism wide
      and often host a variety of additional related genetic, genomic, or phenotypic
      information. In this chapter, we will present some of the features of plant
      molecular genetic marker databases, highlight the various types of marker
      resources, and predict the potential future direction of crop marker databases. 

PMID- 25373749
TI  - Plant genotyping using fluorescently tagged inter-simple sequence repeats
      (ISSRs): basic principles and methodology.
AB  - Inter-simple sequence repeat PCR (ISSR-PCR) is a fast, inexpensive genotyping
      technique based on length variation in the regions between microsatellites. The
      method requires no species-specific prior knowledge of microsatellite location or
      composition. Very small amounts of DNA are required, making this method ideal for
      organisms of conservation concern, or where the quantity of DNA is extremely
      limited due to organism size. ISSR-PCR can be highly reproducible but requires
      careful attention to detail. Optimization of DNA extraction, fragment
      amplification, and normalization of fragment peak heights during fluorescent
      detection are critical steps to minimizing the downstream time spent verifying
      and scoring the data. 

PMID- 25373750
TI  - SSR genotyping.
AB  - SSR genotyping involves the use of simple sequence repeats (SSRs) as DNA markers.
      SSRs, also called microsatellites, are a type of repetitive DNA sequence
      ubiquitous in most plant genomes. SSRs contain repeats of a motif sequence 1-6 bp
      in length. Due to this structure SSRs frequently undergo mutations, mainly due to
      DNA polymerase errors, which involve the addition or subtraction of a repeat
      unit. Hence, SSR sequences are highly polymorphic and may be readily used for
      detection of allelic variation within populations. SSRs are present within both
      genic and nongenic regions and are occasionally transcribed, and hence may be
      identified in expressed sequence tags (ESTs) as well as more commonly in nongenic
      DNA sequences. SSR genotyping involves the design of DNA-based primers to amplify
      SSR sequences from extracted genomic DNA, followed by amplification of the SSR
      repeat region using polymerase chain reaction, and subsequent visualization of
      the resulting DNA products, usually using gel electrophoresis. These procedures
      are described in this chapter. SSRs have been one of the most favored molecular
      markers for plant genotyping in the last 20 years due to their high levels of
      polymorphism, wide distribution across most plant genomes, and ease of use and
      will continue to be a useful tool in many species for years to come. 

PMID- 25373751
TI  - Genotyping analysis using an RFLP assay.
AB  - RFLP (Restriction Fragment Length Polymorphism) is a commonly used technique that
      can be used for genotyping for nearly all organisms, including plants, animals,
      and humans. RFLP is widely used in genetic and genomic research, such as genome
      mapping and gene identification. The technique involves DNA digestion, gel
      electrophoresis, capillary transfer of DNA, and southern hybridization. In this
      chapter, we aim to give a detailed introduction of how to perform RFLPs for
      identifying genotypes. 

PMID- 25373752
TI  - DNA barcoding for plants.
AB  - DNA barcoding uses specific regions of DNA in order to identify species.
      Initiatives are taking place around the world to generate DNA barcodes for all
      groups of living organisms and to make these data publically available in order
      to help understand, conserve, and utilize the world's biodiversity. For land
      plants the core DNA barcode markers are two sections of coding regions within the
      chloroplast, part of the genes, rbcL and matK. In order to create high quality
      databases, each plant that is DNA barcoded needs to have a herbarium voucher that
      accompanies the rbcL and matK DNA sequences. The quality of the DNA sequences,
      the primers used, and trace files should also be accessible to users of the data.
      Multiple individuals should be DNA barcoded for each species in order to check
      for errors and allow for intraspecific variation. The world's herbaria provide a
      rich resource of already preserved and identified material and these can be used
      for DNA barcoding as well as by collecting fresh samples from the wild. These
      protocols describe the whole DNA barcoding process, from the collection of plant
      material from the wild or from the herbarium, how to extract and amplify the DNA,
      and how to check the quality of the data after sequencing. 

PMID- 25373753
TI  - Multiplexed digital gene expression analysis for genetical genomics in large
      plant populations.
AB  - Digital gene expression (DGE) analysis is a cost-effective method for large-scale
      quantitative transcriptome analysis using second generation sequencing. Here we
      describe how adaptation of DGE with barcode indexing in large segregating plant
      populations of over 100 genotypes can be applied for successful expression QTL
      (eQTL) and gene expression network analysis to develop transcript-based markers
      for breeding. 

PMID- 25373754
TI  - SNP genotyping by heteroduplex analysis.
AB  - Heteroduplex-based genotyping methods have proven to be technologically effective
      and economically efficient for low- to medium-range throughput single-nucleotide
      polymorphism (SNP) determination. In this chapter we describe two protocols that
      were successfully applied for SNP detection and haplotype analysis of candidate
      genes in association studies. The protocols involve (1) enzymatic mismatch
      cleavage with endonuclease CEL1 from celery, associated with fragment separation
      using capillary electrophoresis (CEL1 cleavage), and (2) differential retention
      of the homo/heteroduplex DNA molecules under partial denaturing conditions on ion
      pair reversed-phase liquid chromatography (dHPLC). Both methods are complementary
      since dHPLC is more versatile than CEL1 cleavage for identifying multiple SNP per
      target region, and the latter is easily optimized for sequences with fewer SNPs
      or small insertion/deletion polymorphisms. Besides, CEL1 cleavage is a powerful
      method to localize the position of the mutation when fragment resolution is done
      using capillary electrophoresis. 

PMID- 25373755
TI  - Application of the high-resolution melting technique for gene mapping and SNP
      detection in plants.
AB  - Identifying DNA variations associated with important agronomic traits is a major
      focus for plant biologists today. Modern crop breeders use molecular markers
      widely as tools for selecting new varieties more rapidly and efficiently. High
      Resolution Melting (HRM) is frequently selected as the method of choice to
      rapidly and cost effectively detect and genotype SNPs. These SNPs can be used for
      gene mapping studies and routinely by breeders. 

PMID- 25373756
TI  - Challenges of genotyping polyploid species.
AB  - Most plant species are known to be either ancient or recent polyploids,
      containing more than one genome as a result of past interspecific hybridization
      events (allopolyploidy) and/or genome doubling (autopolyploidy). Genotyping in
      polyploid species offers a set of unique challenges. Most molecular marker
      methodologies are made more complex by polyploidy, as multilocus alleles are
      generally produced when a single locus is targeted. Genotyping by sequencing is
      also more challenging in polyploids, with problematic assemblies of duplicated
      regions and difficulties in distinguishing between inter- and intragenomic
      polymorphisms. Strategies for identifying and overcoming the challenges of
      polyploidy in plant genotyping are proposed. 

PMID- 25373757
TI  - Genomic reduction assisted single nucleotide polymorphism discovery using 454
      pyrosequencing.
AB  - We report the development of a simple genomic reduction protocol based on 454
      pyrosequencing technology that discovers large numbers of single nucleotide
      polymorphisms (SNP) from pooled DNA samples. The method is based on the
      conservation of restriction endonuclease sites across samples and biotin
      separation for genomic reduction and the addition of multiplex identifier (MID)
      barcodes to each of the pooled samples to allow for postsequencing deconvolution
      of the pooled DNA fragments and SNP discovery. 

PMID- 25373758
TI  - Inter-SINE Amplified Polymorphism (ISAP) for rapid and robust plant genotyping.
AB  - The unambiguous differentiation of crop genotypes is often laborious or
      expensive. A rapid, robust, and cost-efficient marker system is required for
      routine genotyping in plant breeding and marker-assisted selection. We describe
      the Inter-SINE Amplified Polymorphism (ISAP) system that is based on standard
      molecular methods resulting in genotype-specific fingerprints at high resolution.
      These markers are derived from Short Interspersed Nuclear Elements (SINEs) which
      are dispersed repetitive sequences present in most if not all plant genomes and
      can be efficiently extracted from plant genome sequences. The ISAP method was
      developed on potato as model plant but is also transferable to other plant
      species. 

PMID- 25373760
TI  - Gene analysis using mass spectrometric cleaved amplified polymorphic sequence (MS
      CAPS) with matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF).
AB  - Mass spectrometric cleaved amplified polymorphic sequence (MS-CAPS) is a method
      for detecting genes using a combination of short PCR and matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). MS-CAPS
      can identify a single nucleotide polymorphism (SNP) in less than one hour and is
      suitable for plants, animals, bacteria, and food. 

PMID- 25373759
TI  - Screening of mutations by TILLING in plants.
AB  - TILLING (Targeting Induced Local Lesions IN Genomes) is a well-known reverse
      genetics technique designed to detect unknown SNPs (single nucleotide
      polymorphisms) in genes of interest using an enzymatic digestion and is widely
      employed in plant and animal genomics. The main advantage of this technique is
      that it allows for the high-throughput identification of an allelic series of
      mutants with a range of modified functions for a particular gene. In this
      chapter, we aim to give a detailed introduction of how to establish a TILLING
      platform for identifying mutants in plants, including generation of a large
      mutant population, DNA and seed library preparation, mutation identification
      based on a LI-COR4300 DNA analyzer, and confirmation of functions of the mutated
      genes. 

PMID- 25373761
TI  - Quantitative SNP genotyping of polyploids with MassARRAY and other platforms.
AB  - Accurate genotyping is essential for building genetic maps and performing genome
      assembly of polyploid species. Recent high-throughput techniques, such as
      Illumina GoldenGateTM and Sequenom iPLEX MassARRAY(r), have made it possible to
      accurately estimate the relative abundances of different alleles even when the
      ploidy of the population is unknown. Here we describe the experimental methods
      for collecting these relative allele intensities and then demonstrate the
      practical concerns for inferring genotypes using Bayesian inference via the
      software package SuperMASSA. 

PMID- 25373762
TI  - SNP genotyping using KASPar assays.
AB  - In a separate chapter we describe a simple method for single nucleotide
      polymorphism (SNP) discovery using genomic reduction. Here we describe a scalable
      and cost-effective SNP genotyping method based on KBioscience's competitive
      allele-specific PCR amplification of target sequences and endpoint fluorescence
      genotyping (KASParTM) using a FRET capable plate reader or Fluidigm's dynamic
      array high-throughput platform. 

PMID- 25373763
TI  - Skim-based genotyping by sequencing.
AB  - Genotyping by sequencing (GBS) is a relatively new method used to determine the
      differences in the genetic makeup of individuals. Its novelty stems from a
      combination of two already available methods: genotyping and next-generation
      sequencing. Depending on the individual study design GBS protocols can take
      multiple forms, however most share a sequence of core steps that have to be
      undertaken. These include: sequencing of the DNA from the individuals of interest
      (usually two parents of a mapping population and their progeny), mapping of the
      sequencing reads to the reference sequence, SNP calling and filtering, SNP
      genotyping and imputation, followed by haplotype identification and downstream
      analysis. GBS has a range of applications from general marker discovery,
      haplotype identification, and recombination characterization to quantitative
      trait locus (QTL) analysis, genome-wide association studies (GWAS), and genomic
      selection (GS). It has already been applied to a range of plant species
      including: rice, maize, artichoke, and Arabidopsis thaliana. It is a promising
      approach which is likely to provide new and important insights into plant
      biology. 

PMID- 25373764
TI  - The restriction enzyme target approach to genotyping by sequencing (GBS).
AB  - The modified genotyping by sequencing method described here emphasizes verifying
      the success of each library ligation by performing individual PCRs, before
      preparing the pool of barcoded amplicons to be sequenced. Although this extra
      step might seem excessive, it will give peace of mind to the researcher knowing
      each individual is represented in the data set and avoid additional data
      imputation at the analysis stage. 

PMID- 25373765
TI  - Methods for the design, implementation, and analysis of illumina infiniumTM SNP
      assays in plants.
AB  - The advent of Next-Generation sequencing-by-synthesis technologies has fuelled
      SNP discovery, genotyping, and screening of populations in myriad ways for many
      species, including various plant species. One technique widely applied to
      screening a large number of SNP markers over a large number of samples is the
      Illumina InfiniumTM assay. 

PMID- 25373766
TI  - Use of the Illumina GoldenGate assay for single nucleotide polymorphism (SNP)
      genotyping in cereal crops.
AB  - Highly parallel genotyping assays, such as the GoldenGate assay developed by
      Illumina, capable of interrogating up to 3,072 single nucleotide polymorphisms
      (SNPs) simultaneously, have greatly facilitated genome-wide studies, particularly
      for crops with large and complex genome structures. In this report, we provide
      detailed information and guidelines regarding genomic DNA preparation, SNP assay
      design, SNP assay protocols, and genotype calling using Illumina's GenomeStudio
      software. 

PMID- 25373767
TI  - Facial and bodily emotion recognition in multiple sclerosis: the role of
      alexithymia and other characteristics of the disease.
AB  - Multiple sclerosis (MS) may be associated with impaired perception of facial
      emotions. However, emotion recognition mediated by bodily postures has never been
      examined in these patients. Moreover, several studies have suggested a relation
      between emotion recognition impairments and alexithymia. This is in line with the
      idea that the ability to recognize emotions requires the individuals to be able
      to understand their own emotions. Despite a deficit in emotion recognition has
      been observed in MS patients, the association between impaired emotion
      recognition and alexithymia has received little attention. The aim of this study
      was, first, to investigate MS patient's abilities to recognize emotions mediated
      by both facial and bodily expressions and, second, to examine whether any
      observed deficits in emotions recognition could be explained by the presence of
      alexithymia. Thirty patients with MS and 30 healthy matched controls performed
      experimental tasks assessing emotion discrimination and recognition of facial
      expressions and bodily postures. Moreover, they completed questionnaires
      evaluating alexithymia, depression, and fatigue. First, facial emotion
      recognition and, to a lesser extent, bodily emotion recognition can be impaired
      in MS patients. In particular, patients with higher disability showed an
      impairment in emotion recognition compared with patients with lower disability
      and controls. Second, their deficit in emotion recognition was not predicted by
      alexithymia. Instead, the disease's characteristics and the performance on some
      cognitive tasks significantly correlated with emotion recognition. Impaired
      facial emotion recognition is a cognitive signature of MS that is not dependent
      on alexithymia.

PMID- 25373768
TI  - Biomarkers for early diagnosis of pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma is an aggressive malignancy with a 5-year
      survival rate of approximately 5%. The lack of established strategies for early
      detection contributes to this poor prognosis. Although several novel candidate
      biomarkers have been proposed for earlier diagnosis, none have been adopted into
      routine clinical use. In this review, the authors examine the challenges
      associated with finding new pancreatic cancer diagnostic biomarkers and explore
      why translation of biomarker research for patient benefit has thus far failed.
      The authors also review recent progress and highlight advances in the
      understanding of the biology of pancreatic cancer that may lead to improvements
      in biomarker detection and implementation. 

PMID- 25373769
TI  - Providing emergency care and assessing a patient triage system in a referral
      hospital in Somaliland: a cross-sectional study.
AB  - BACKGROUND: In resource-poor settings, where health systems are frequently
      stretched to their capacity, access to emergency care is often limited. Triage
      systems have been proposed as a tool to ensure efficiency and optimal use of
      emergency resources in such contexts. However, evidence on the practice of
      emergency care and the implementation of triage systems in such settings, is
      scarce. This study aimed to assess emergency care provision in the Burao district
      hospital in Somaliland, including the application of the South African Triage
      Scale (SATS) tool. METHODS: A cross-sectional descriptive study was undertaken.
      Routine programme data of all patients presenting at the Emergency Department
      (ED) of Burao Hospital during its first year of service (January to December
      2012) were analysed. The American College of Surgeons Committee on Trauma
      (ACSCOT) indicators were used as SATS targets for high priority emergency cases
      ("high acuity" proportion), overtriage and undertriage (with thresholds of >25%,
      <50% and <10%, respectively). RESULTS: In 2012, among 7212 patients presented to
      the ED, 41% were female, and 18% were aged less than five. Only 21% of these
      patients sought care at the ED within 24 hours of developing symptoms. The high
      acuity proportion was 22.3%, while the overtriage (40%) and undertriage (9%)
      rates were below the pre-set thresholds. The overall mortality rate was 1.3% and
      the abandon rate 2.0%. The outcomes of patients corresponds well with the color
      code assigned using SATS. CONCLUSION: This is the first study assessing the
      implementation of SATS in a post-conflict and resource-limited African setting
      showing that most indicators met the expected standards. In particular, specific
      attention is needed to improve the relatively low rate of true emergency cases,
      delays in patient presentation and in timely provision of care within the ED.
      This study also highlights the need for development of emergency care thresholds
      that are more adapted to resource-poor contexts. These issues are discussed.

PMID- 25373770
TI  - Cell tracking using (19)F magnetic resonance imaging: technical aspects and
      challenges towards clinical applications.
AB  - (19)F MRI is emerging as a new imaging technique for cell tracking. It is
      particularly attractive because of its potential for direct and precise cell
      quantification. The most important challenge towards in vivo applications is the
      sensitivity of the technique, i.e. the detection limit in a reasonable imaging
      time. Optimal sensitivity can be achieved with dedicated (19)F compounds together
      with specifically adapted hardware and acquisition methods. In this paper we
      introduce the (19)F MRI technique focusing on these key sensitivity issues and
      review the state-of-the-art of (19)F MRI and developments towards its clinical
      use. We calculate (19)F detection limits reported in preclinical cell and
      clinical (19)F drug studies in terms of tissue concentration in a 1 cm(3) voxel,
      as an alternate way to compare detection limits. We estimate that a tissue
      concentration of a few millimoles per litre (mM) of (19)F is required for a human
      study at a resolution of 1 cm(3).

PMID- 25373771
TI  - Calluses flex their muscles to align bone fragments during fracture repair.
AB  - Neonatal animals spontaneously reduce fractures, yet the mechanical forces
      influencing this process are poorly understood. In this issue of Developmental
      Cell, Rot et al. (2014) show that muscle and the fracture callus actively
      position fractured neonatal bone fragments to restore their alignment,
      highlighting the multifaceted roles of mechanical cues in skeletal regeneration. 

PMID- 25373772
TI  - Desmosomal hotspots, microtubule delivery, and cardiac arrhythmogenesis.
AB  - Microtubules can target proteins such as Connexin43 to plasma membrane
      subdomains. Patel et al. (2014) now show that the structural desmosome complex
      participates in targeted trafficking of membrane components through interactions
      between the microtubule network and the N terminus of desmoplakin, a region that
      is a pathogenic mutation hotspot. 

PMID- 25373773
TI  - Outside in: inversion of cell polarity controls epithelial lumen formation.
AB  - Establishment of cell polarity is important for epithelial lumen formation, and
      the molecular mechanisms directing this process are only partially understood. In
      this issue of Developmental Cell, Bryant et al. (2014) show that disassembly,
      membrane translocation, and reassembly of podocalyxin complexes controls
      epithelial cell polarization and lumen formation in 3D matrices. 

PMID- 25373774
TI  - Multigenerational chromatin marks: no enzymes need apply.
AB  - Epigenetic memory stably maintains and transmits information during genome
      replication. Recently in Science, Gaydos et al. (2014) show that repressive
      chromatin marks exhibit transgenerational stability in the absence of chromatin
      modifying enzymes in Caenorhabditis elegans, in contrast to work in flies
      suggesting that such proteins mediate stable inheritance of epigenetic
      modifications. 

PMID- 25373775
TI  - The C. elegans SNAPc component SNPC-4 coats piRNA domains and is globally
      required for piRNA abundance.
AB  - The Piwi/Piwi-interacting RNA (piRNA) pathway protects the germline from the
      activity of foreign sequences such as transposons. Remarkably, tens of thousands
      of piRNAs arise from a minimal number of discrete genomic regions. The extent to
      which clustering of these small RNA genes contributes to their coordinated
      expression remains unclear. We show that C. elegans SNPC-4, the Myb-like DNA
      binding subunit of the small nuclear RNA activating protein complex, binds piRNA
      clusters in a germline-specific manner and is required for global piRNA
      expression. SNPC-4 localization is mutually dependent with localization of piRNA
      biogenesis factor PRDE-1. SNPC-4 exhibits an atypical widely distributed binding
      pattern that "coats" piRNA domains. Discrete peaks within the domains occur
      frequently at RNA-polymerase-III-occupied transfer RNA (tRNA) genes, which have
      been implicated in chromatin organization. We suggest that SNPC-4 binding
      establishes a positive expression environment across piRNA domains, providing an
      explanation for the conserved clustering of individually transcribed piRNA genes.

PMID- 25373776
TI  - A mechanical Jack-like Mechanism drives spontaneous fracture healing in neonatal
      mice.
AB  - Treatment of fractured bones involves correction of displacement or angulation,
      known as reduction. However, angulated long-bone fractures in infants often heal
      and regain proper morphology spontaneously, without reduction. To study the
      mechanism underlying spontaneous regeneration of fractured bones, we left humeral
      fractures induced in newborn mice unstabilized, and rapid realignment of
      initially angulated bones was seen. This realignment was surprisingly not
      mediated by bone remodeling, but instead involved substantial movement of the two
      fragments prior to callus ossification. Analysis of gene expression profiles,
      cell proliferation, and bone growth revealed the formation of a functional,
      bidirectional growth plate at the concave side of the fracture. This growth plate
      acts like a mechanical jack, generating opposing forces that straighten the two
      fragments. Finally, we show that muscle force is important in this process, as
      blocking muscle contraction disrupts growth plate formation, leading to premature
      callus ossification and failed reduction. 

PMID- 25373778
TI  - Antioxidant signaling involving the microtubule motor KIF12 is an intracellular
      target of nutrition excess in beta cells.
AB  - Beta cell injury due to oxidative stress is a typical etiology of diabetes caused
      by nutritional excess, but its precise mechanism remains largely elusive. Here,
      we demonstrate that the microtubule motor KIF12 mediates an antioxidant cascade
      in beta cells as an intracellular target of excess fat intake or "lipotoxicity."
      KIF12 knockout mice suffer from hypoinsulinemic glucose intolerance due to
      increased beta cell oxidative stress. Using this model, we identified an
      antioxidant signaling cascade involving KIF12 as a scaffold for the transcription
      factor Sp1. The stabilization of nascent Sp1 appeared to be essential for proper
      peroxisomal function by enhancing Hsc70 expression, and the pharmacological
      induction of Hsc70 expression with teprenone counteracted the oxidative stress.
      Because KIF12 is transcriptionally downregulated by chronic exposure to fatty
      acids, this antioxidant cascade involving KIF12 and Hsc70 is proposed to be a
      critical target of nutritional excess in beta cells in diabetes. 

PMID- 25373777
TI  - Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C.
      elegans.
AB  - Members of the Wnt family of secreted signaling proteins are key regulators of
      cell migration and axon guidance. In the nematode C. elegans, the migration of
      the QR neuroblast descendants requires multiple Wnt ligands and receptors. We
      found that the migration of the QR descendants is divided into three sequential
      phases that are each mediated by a distinct Wnt signaling mechanism. Importantly,
      the transition from the first to the second phase, which is the main determinant
      of the final position of the QR descendants along the anteroposterior body axis,
      is mediated through a cell-autonomous process in which the time-dependent
      expression of a Wnt receptor turns on the canonical Wnt/beta-catenin signaling
      response that is required to terminate long-range anterior migration. Our results
      show that, in addition to direct guidance of cell migration by Wnt morphogenic
      gradients, cell migration can also be controlled indirectly through cell
      intrinsic modulation of Wnt signaling responses. 

PMID- 25373779
TI  - Cofilin-2 controls actin filament length in muscle sarcomeres.
AB  - ADF/cofilins drive cytoskeletal dynamics by promoting the disassembly of "aged"
      ADP-actin filaments. Mammals express several ADF/cofilin isoforms, but their
      specific biochemical activities and cellular functions have not been studied in
      detail. Here, we demonstrate that the muscle-specific isoform cofilin-2 promotes
      actin filament disassembly in sarcomeres to control the precise length of thin
      filaments in the contractile apparatus. In contrast to other isoforms, cofilin-2
      efficiently binds and disassembles both ADP- and ATP/ADP-Pi-actin filaments. We
      mapped surface-exposed cofilin-2-specific residues required for ATP-actin binding
      and propose that these residues function as an "actin nucleotide-state sensor"
      among ADF/cofilins. The results suggest that cofilin-2 evolved specific
      biochemical and cellular properties that allow it to control actin dynamics in
      sarcomeres, where filament pointed ends may contain a mixture of ADP- and ATP/ADP
      Pi-actin subunits. Our findings also offer a rationale for why cofilin-2
      mutations in humans lead to myopathies. 

PMID- 25373780
TI  - A genomic Multiprocess survey of machineries that control and link cell shape,
      microtubule organization, and cell-cycle progression.
AB  - Understanding cells as integrated systems requires that we systematically
      decipher how single genes affect multiple biological processes and how processes
      are functionally linked. Here, we used multiprocess phenotypic profiling,
      combining high-resolution 3D confocal microscopy and multiparametric image
      analysis, to simultaneously survey the fission yeast genome with respect to three
      key cellular processes: cell shape, microtubule organization, and cell-cycle
      progression. We identify, validate, and functionally annotate 262 genes
      controlling specific aspects of those processes. Of these, 62% had not been
      linked to these processes before and 35% are implicated in multiple processes.
      Importantly, we identify a conserved role for DNA-damage responses in controlling
      microtubule stability. In addition, we investigate how the processes are
      functionally linked. We show unexpectedly that disruption of cell-cycle
      progression does not necessarily affect cell size control and that distinct
      aspects of cell shape regulate microtubules and vice versa, identifying important
      systems-level links across these processes. 

PMID- 25373782
TI  - Whole mitochondrial genome sequence of a rat rheumatoid arthritis E3 strain.
AB  - We sequenced a complete mitochondrial genome sequence of a rat rheumatoid
      arthritis disease E3 strain for the first time. The total length of the
      mitogenome was 16,305 bp and coding 13 protein-coding genes, 2 ribosomal RNA
      genes, 22 transfer RNA genes. This mitochondrial genome sequence will provide new
      genetic resource into rheumatoid arthritis disease.

PMID- 25373781
TI  - Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting
      ligand-specific canonical wnt signaling.
AB  - Canonical Wnt signaling in endothelial cells (ECs) is required for
      vascularization of the central nervous system (CNS) and for formation and
      maintenance of barrier properties unique to CNS vasculature. Gpr124 is an orphan
      member of the adhesion G protein-coupled receptor family that is expressed in ECs
      and is essential for CNS angiogenesis and barrier formation via an unknown
      mechanism. Using canonical Wnt signaling assays in cell culture and genetic loss-
      and gain-of-function experiments in mice, we show that Gpr124 functions as a
      coactivator of Wnt7a- and Wnt7b-stimulated canonical Wnt signaling via a Frizzled
      receptor and Lrp coreceptor and that Gpr124-stimulated signaling functions in
      concert with Norrin/Frizzled4 signaling to control CNS vascular development.
      These experiments identify Gpr124 as a ligand-specific coactivator of canonical
      Wnt signaling. 

PMID- 25373783
TI  - Impact of SIN-1-derived peroxynitrite flux on endothelial cell redox homeostasis
      and bioenergetics: protective role of diphenyl diselenide via induction of
      peroxiredoxins.
AB  - Increased production of reactive nitrogen (RNS) and oxygen (ROS) species and its
      detrimental effect to mitochondria are associated with endothelial dysfunction.
      This study was designed to determine the effect of a peroxynitrite flux, promoted
      by 1,3-morpholinosydnonimine (SIN-1), in mitochondrial function and some redox
      homeostasis parameters in bovine aortic endothelial cells (BAEC). Moreover, the
      effect of diphenyl diselenide (PhSe)2, a simple organic selenium compound, in
      preventing peroxynitrite-mediated cytotoxicity was also investigated. Our results
      showed that overnight exposure to SIN-1 (250 MUM) caused a profound impairment of
      oxygen consumption, energy generation and reserve capacity in mitochondria of
      BAEC. Mitochondrial dysfunction resulted in an additional intracellular
      production of peroxynitrite, amplifying the phenomenon and leading to changes in
      redox homeostasis. Moreover, we observed an extensive decline in mitochondrial
      membrane potential (DeltaPsim) induced by peroxynitrite and this event was
      associated with apoptotic-type cell death. Alternatively, the pretreatment of
      BAEC with (PhSe)2, hindered peroxynitrite-mediated cell damage by preserving
      mitochondrial and endothelial function and consequently preventing apoptosis. The
      protective effect of (PhSe)2 was related to its ability to improve the
      intracellular redox state by increasing the expression of different isoforms of
      peroxiredoxins (Prx-1-3), efficient enzymes in peroxynitrite detoxification.

PMID- 25373784
TI  - Evaluation of a universal coverage bed net distribution campaign in four
      districts in Sofala Province, Mozambique.
AB  - BACKGROUND: Malaria is the leading cause of death in Mozambique in children under
      five years old. In 2009, Mozambique developed a novel bed net distribution model
      to increase coverage, based on assumptions about sleeping patterns. The coverage
      and impact of a bed net distribution campaign using this model in four districts
      in Sofala Province, Mozambique was evaluated. METHODS: Paired household, cross
      sectional surveys were conducted one month after the 2010 distribution of 140,000
      bed nets and again 14 months after the campaign in 2011. During household visits,
      malaria blood smears were performed and haemoglobin levels were assessed on
      children under five and data on bed net ownership, access and use were collected;
      these indicators were analysed at individual, household and community levels.
      Logistic regression was used to evaluate predictors of malaria infection and
      anaemia. RESULTS: The campaign reached 98% (95% CI: 97-99%) of households
      registered during the precampaign listing, with 81% (95% CI: 77-85%) of sleeping
      spaces covered by campaign bed nets and 85% (95% CI: 81-88%) of the population
      sleeping in a sleeping space with a campaign bed net designated for the sleeping
      space. One year after the campaign, 65% (95% CI: 57-72%) of sleeping spaces were
      observed to have hanging bed nets. The proportion of sleeping spaces for which
      bed nets were reported used four or more times per week was 65% (95% CI: 56-74%)
      in the wet season and 60% (95% CI: 52-68%) in the dry season. Malaria
      parasitaemia prevalence in children under five years old was 47% (95% CI: 40-54%)
      in 2010 and 36% (95% CI: 27-45%) in 2011. Individual-level malaria infection and
      anaemia were significantly associated with community-level use of bed nets.
      CONCLUSIONS: The campaign using the novel distribution model achieved high
      coverage, although usage was not uniformly high. A significant decrease in
      malaria parasitaemia prevalence a year after the campaign was not observed, but
      community-level use of bed nets was significantly associated with a reduced risk
      for malaria infection and anaemia in children under five.

PMID- 25373785
TI  - Down-regulation of miR-203 induced by Helicobacter pylori infection promotes the
      proliferation and invasion of gastric cancer by targeting CASK.
AB  - Several microRNAs (miRNA) have been implicated in H. pylori related gastric
      cancer (GC). However, the molecular mechanism of miRNAs in GC has not been fully
      understood. In this study, we reported that miR-203 is significantly down
      regulated in H. pylori positive tissues and cells and in tumor tissues with
      important functional consequences. Ectopic expression of miR-203 dramatically
      suppressed cell proliferation and invasion. We found that miR-203 strongly
      reduced the expression of CASK oncogene in GC cells. Similar to the restoring miR
      203 expression, CASK down-regulation inhibited cell growth and invasion, whereas
      CASK over-expression rescued the suppressive effect of miR-203. These results can
      also be found in nude mice. In clinical specimens, CASK was over-expressed in
      tumors and H. pylori positive tissues and its mRNA levels were inversely
      correlated with miR-203 expression. Taken together, our results indicated that
      miR-203 functions as a growth-suppressive miRNA in H. pylori related GC, and that
      its suppressive effects are mediated mainly by repressing CASK expression. 

PMID- 25373786
TI  - Nasopharyngeal carcinoma presenting with rapidly progressive severe visual
      disturbance: a case report.
AB  - INTRODUCTION: Nasopharyngeal carcinoma is one of the most difficult tumors to
      diagnose correctly at the initial phase because of the occasional lack of nasal
      symptoms. The perineural spread of the trigeminal nerve is one of the most common
      and important routes in the intracranial paracavernous extension of
      nasopharyngeal carcinoma, but visual loss is very rare. CASE PRESENTATION: We
      report the case of a 54-year-old Japanese man with nasopharyngeal carcinoma, who
      presented with rapid and severe disturbance of left monocular visual acuity and
      eye movement with a 10-month history of ipsilateral otitis media and facial pain.
      Magnetic resonance imaging revealed a lesion in the left fossa of Rosenmuller,
      pterygopalatine fossa, sphenoid and ethmoid sinus, and the left cavernous sinus
      extending to the orbital apex through the superior orbital fissure. The
      histopathological diagnosis was nonkeratinizing undifferentiated nasopharyngeal
      carcinoma. Epstein-Barr virus was detected by in situ hybridization. Although
      focal radiotherapy induced remarkable tumor shrinkage and relieved ocular motor
      disturbance and facial pain, his visual acuity did not improve. CONCLUSION: The
      awareness of cranial nerves in addition to intracranial and orbital apex
      involvement, as in this case, is important for appropriate diagnosis and
      treatment planning of nasopharyngeal carcinoma.

PMID- 25373787
TI  - Circulating tumour cells are linked to plasma D-dimer levels in patients with
      metastatic breast cancer.
AB  - Cancer is a risk factor for venous thromboembolism (VTE). Elevated plasma D-dimer
      and fibrinogen levels are also risk factors for VTE. Furthermore, in patients
      with metastatic breast cancer (MBC), the presence of circulating tumour cells
      (CTCs) is a risk factor for VTE. The relationship between CTCs and D-dimer is
      unknown. The aim of this study was to determine whether CTCs correlate with
      plasma D-dimer level, fibrinogen level, and risk of VTE in MBC. This prospective
      study included 47 MBC patients treated from July 2009 through December 2010 at
      the MD Anderson Cancer Center. CTCs in peripheral blood were detected and
      enumerated using the CellSearch system. D-dimer and fibrinogen were measured in
      plasma at the time of CTC detection. Thirty-three patients (70 %) had >= 1 CTC,
      and 22 patients (47 %) had >= 5 CTCs. Patients with >= 1 CTC or >= 5 CTCs had
      significantly higher mean plasma D-dimer levels (ug/mL) than patients with no
      CTCs and < 5 CTCs (2.48 and 3.31 vs 0.80 and 0.84, respectively; p=0.006 for cut
      off >= 1 CTC and p=0.003 for cut-off >= 5 CTCs). In multivariate analysis,
      presence of CTCs and number of metastases were positively associated with plasma
      D-dimer level. CTCs were not associated with plasma fibrinogen level. At median
      follow-up of 13.5 months, three of 33 patients (9 %) with >= 1 CTC had VTE, vs no
      patients with undetectable CTCs. In conclusion, the presence of CTCs was
      associated with higher levels of plasma D-dimer in MBC patients. This study
      further confirms an association between CTCs and risk of VTE.

PMID- 25373788
TI  - High impact biowastes from South European agro-industries as feedstock for second
      generation biorefineries.
AB  - Availability of bio-based chemicals, materials and energy at reasonable cost will
      be one of the forthcoming issues for the EU economy. In particular, the
      development of technologies making use of alternative resources to fossil fuels
      is encouraged by the current European research and innovation strategy to face
      the societal challenge of natural resource scarcity, fossil resource dependence
      and sustainable economic growth. In this respect, second- generation
      biorefineries, i.e. biorefineries fed with biowastes, appear to be good
      candidates to substitute and replace the present downstream processing scheme.
      Contrary to first-generation biorefineries, which make use of dedicated crops or
      primary cultivations to achieve such a goal, the former employ agricultural,
      industrial, zootechnical, fishery and forestry biowastes as the main feedstock.
      This leaves aside any ethical and social issue generated by first-generation
      approaches, and concomitantly prevents environmental and economical issues
      associated with the disposal of the aforementioned leftovers. Unfortunately, to
      date, a comprehensive and updated mapping of the availability and potential use
      of bioresources for second-generation biorefineries in Europe is missing. This is
      a lack that severely limits R&D and industrial applications in the sector. On the
      other hand, attempts at valorizing the most diverse biowastes dates back to the
      nineteenth century and plenty of information in the literature on their
      sustainable exploitation is available. However, the large majority of these
      investigations have been focused on single fractions of biowastes or single steps
      of biowaste processing, preventing considerations on an integrated and modular
      (cascade) approach for the whole valorization of organic leftovers. This review
      aims at addressing these issues by gathering recent data on (a) some of the main
      high-impact biowastes located in Europe and in particular in its Southern part,
      and (b) the bio-based chemicals, materials and fuels that can be produced from
      such residues. In particular, we focused on those key compounds referred to as
      "chemical platforms", which have been indicated as fundamental to generate the
      large majority of the industrially relevant goods to date. 

PMID- 25373789
TI  - Biocatalysts: application and engineering for industrial purposes.
AB  - Enzymes are widely applied in various industrial applications and processes,
      including the food and beverage, animal feed, textile, detergent and medical
      industries. Enzymes screened from natural origins are often engineered before
      entering the market place because their native forms do not meet the requirements
      for industrial application. Protein engineering is concerned with the design and
      construction of novel enzymes with tailored functional properties, including
      stability, catalytic activity, reaction product inhibition and substrate
      specificity. Two broad approaches have been used for enzyme engineering, namely,
      rational design and directed evolution. The powerful and revolutionary techniques
      so far developed for protein engineering provide excellent opportunities for the
      design of industrial enzymes with specific properties and production of high
      value products at lower production costs. The present review seeks to highlight
      the major fields of enzyme application and to provide an updated overview on
      previous protein engineering studies wherein natural enzymes were modified to
      meet the operational conditions required for industrial application. 

PMID- 25373790
TI  - Experimental design methods for bioengineering applications.
AB  - Experimental design is a form of process analysis in which certain factors are
      selected to obtain the desired responses of interest. It may also be used for the
      determination of the effects of various independent factors on a dependent
      factor. The bioengineering discipline includes many different areas of scientific
      interest, and each study area is affected and governed by many different factors.
      Briefly analyzing the important factors and selecting an experimental design for
      optimization are very effective tools for the design of any bioprocess under
      question. This review summarizes experimental design methods that can be used to
      investigate various factors relating to bioengineering processes. The
      experimental methods generally used in bioengineering are as follows: full
      factorial design, fractional factorial design, Plackett-Burman design, Taguchi
      design, Box-Behnken design and central composite design. These design methods are
      briefly introduced, and then the application of these design methods to study
      different bioengineering processes is analyzed. 

PMID- 25373791
TI  - Development of a novel malarial vaccine design: a hypothetical approach.
AB  - P. falciparum is highly virulent in nature because of its ability to modify the
      infected host red blood cells, adherence to the vascular endothelium and changes
      in antigenicity at different stages. Also slow migration time in the dermal and
      endothelial cells leads to decreased immune response. To overcome the problems,
      there is a need to design a vaccine which increases the migration time of the
      parasite, enhances the immune response, enables recognition of surface antigens
      and causes minimal clinical infection as a side-effect. An ITI-based (Infection
      Treatment Immunization) vaccine development strategy is to be adopted to develop
      this novel vaccine. This will include administration of a liquid solution of
      purified, non-attenuated sporozoites from an infected female Anopheles mosquito,
      AS02A adjuvant and chlorate (a metabolic inhibitor of sulfation that decreases
      the extent of GAG sulfation). To control infection, a drug-cover of artemisinin
      will be administered as a part of the vaccination strategy along with a specific
      protease inhibitor MRT12113 which prevents RBC rupture and reinvasion by the
      parasite. This vaccine will intend to increase the overall migration time of the
      parasite in blood which is otherwise approximately 30 minutes, resulting in an
      overall enhanced immune response. It also intends to reduce parasite invasion in
      cells and their consequent rupture thus preventing the clinical condition
      malaria. 

PMID- 25373793
TI  - Real space probe of short-range interaction between Cr in a ferromagnetic
      semiconductor ZnCrTe.
AB  - The short-range interaction between Cr atoms was directly examined by scanning
      tunneling microscopy measurements on a Zn(0.95)Cr(0.05)Te film. Our measurements
      revealed that a Cr atom formed a localized state within the bandgap of ZnTe and
      this state was broadened for a pair of Cr atoms within a distance of ~ 1 nm.

PMID- 25373792
TI  - Independent origin of c.57 C > T mutation in MIR184 associated with inherited
      corneal and lens abnormalities.

PMID- 25373794
TI  - Orbital Asian summer monsoon dynamics revealed using an isotope-enabled global
      climate model.
AB  - The Asian summer monsoon dynamics at the orbital scale are a subject of
      considerable debate. The validity of Asian speleothem delta(18)O records as a
      proxy for summer monsoon intensity is questioned together with the ultimate
      forcing and timing of the monsoon. Here, using the results of a 150,000-year
      transient simulation including water isotopes, we demonstrate that Asian
      speleothem delta(18)O records are not a valid proxy for summer monsoon intensity
      only at the orbital timescale. Rather, our results show that these records
      reflect annual variations in hydrologic processes and circulation regime over a
      large part of the Indo-Asian region. Our results support the role of internal
      forcing, such as sea surface temperature in the equatorial Pacific, to modulate
      the timing of monsoon precipitation recorded in paleo-proxies inside the Asian
      region. 

PMID- 25373795
TI  - Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma
      and Transjugular Intrahepatic Portosystemic Shunts.
AB  - PURPOSE: Locoregional therapy for hepatocellular carcinoma (HCC) can be
      challenging in patients with a transjugular intrahepatic portosystemic shunt
      (TIPS). This study compares safety and imaging response of ablation,
      chemoembolization, radioembolization, and supportive care in patients with both
      TIPS and HCC. METHODS: This retrospective study included 48 patients who had both
      a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60%) underwent treatment for
      HCC, and 19/48 (40%) received best supportive care (i.e., symptomatic management
      only). While etiology of cirrhosis and indication for TIPS were similar between
      the two groups, treated patients had better baseline liver function (34 vs. 67%
      Child-Pugh class C). Tumor characteristics were similar between the two groups. A
      total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90
      radioembolizations were performed on 29 patients. RESULTS: Ablation procedures
      resulted in low rates of hepatotoxicity and clinical toxicity. Post
      embolization/ablation syndrome occurred more frequently in patients undergoing
      chemoembolization than ablation (47 vs. 15%). Significant hepatic dysfunction
      occurred more frequently in the chemoembolization group than the ablation group.
      Follow-up imaging response showed objective response in 100% of ablation
      procedures, 67% of radioembolization procedures, and 50% of chemoembolization
      procedures (p = 0.001). When censored for OLT, patients undergoing treatment
      survived longer than patients receiving supportive care (2273 v. 439 days, p =
      0.001). CONCLUSIONS: Ablation appears to be safe and efficacious for HCC in
      patients with TIPS. Catheter-based approaches are associated with potential
      increased toxicity in this patient population. Chemoembolization appears to be
      associated with increased toxicity compared to radioembolization.

PMID- 25373796
TI  - Randomized comparison of selective internal radiotherapy (SIRT) versus drug
      eluting bead transarterial chemoembolization (DEB-TACE) for the treatment of
      hepatocellular carcinoma.
AB  - PURPOSE: To prospectively compare SIRT and DEB-TACE for treating hepatocellular
      carcinoma (HCC). METHODS: From 04/2010-07/2012, 24 patients with histologically
      proven unresectable N0, M0 HCCs were randomized 1:1 to receive SIRT or DEB-TACE.
      SIRT could be repeated once in case of recurrence; while, TACE was repeated every
      6 weeks until no viable tumor tissue was detected by MRI or contraindications
      prohibited further treatment. Patients were followed-up by MRI every 3 months;
      the final evaluation was 05/2013. RESULTS: Both groups were comparable in
      demographics (SIRT: 8males/4females, mean age 72 +/- 7 years; TACE:
      10males/2females, mean age 71 +/- 9 years), initial tumor load (1 patient >=25 %
      in each group), and BCLC (Barcelona Clinic Liver Cancer) stage (SIRT: 12*B; TACE
      1*A, 11*B). Median progression-free survival (PFS) was 180 days for SIRT versus
      216 days for TACE patients (p = 0.6193) with a median TTP of 371 days versus 336
      days, respectively (p = 0.5764). Median OS was 592 days for SIRT versus 788 days
      for TACE patients (p = 0.9271). Seven patients died in each group. Causes of
      death were liver failure (n = 4 SIRT group), tumor progression (n = 4 TACE
      group), cardiovascular events, and inconclusive (n = 1 in each group).
      CONCLUSIONS: No significant differences were found in median PFS, OS, and TTP.
      The lower rate of tumor progression in the SIRT group was nullified by a greater
      incidence of liver failure. This pilot study is the first prospective randomized
      trial comparing SIRT and TACE for treating HCC, and results can be used for
      sample size calculations of future studies.

PMID- 25373797
TI  - Regional Radiation Pneumonitis After SIRT of a Subcapsular Liver Metastasis: What
      is the Effect of Direct Beta Irradiation?
AB  - We herein present a patient undergoing selective internal radiation therapy with
      an almost normal lung shunt fraction of 11.5%, developing histologically proven
      radiation pneumonitis. Due to a predominance of pulmonary consolidations in the
      right lower lung and its proximity to a large liver metastases located in the
      dome of the right liver lobe a Monte Carlo simulation was performed to estimate
      the effect of direct irradiation of the lung parenchyma. According to our
      calculations direct irradiation seems negligible and RP is almost exclusively due
      to ectopic draining of radioactive spheres.

PMID- 25373798
TI  - Outcomes of AV Fistulas and AV Grafts after Interventional Stent-Graft Deployment
      in Haemodialysis Patients.
AB  - PURPOSE: The study was designed to assess outcomes of arteriovenous (AV) accesses
      after interventional stent-graft deployment in haemodialysis patients. MATERIALS
      AND METHODS: 63 haemodialysis patients with 66 AV fistulas and AV grafts were
      treated by interventional stent-graft deployment from 2006 to 2012 at our
      hospital. Data of these patients were retrospectively analysed for location of
      deployed stent-grafts, occurrence and location of (re-)stenosis and (re
      )thrombosis. Complex stenosis was the most frequent indication for stent-graft
      deployment (45.5%), followed by complications of angioplasty with vessel rupture
      or dissection (31.8%). RESULTS: A high rate of procedural success was achieved
      (98.5%). The most frequent location of the deployed stent-graft was the draining
      vein (66.7%). Stent-graft deployment was more frequent in AV grafts than in AV
      fistulas. Primary patency was 45.5% at 6 month, 31.3% at 12 month and 19.2% at 24
      month. Primary patency was significantly better for AV fistulas than for AV
      grafts with deployed stent-grafts. Patency of the deployed stent-graft was much
      better than overall AV access primary patency with deployed stent-graft. Re
      stenosis with thrombosis was the most frequent indication for re-intervention.
      Most frequent location of re-stenosis was the draining vein (37.1%), followed by
      stenosis at the AV access (29.5%) and the deployed stent-graft (23.5%).
      CONCLUSION: Re-stenosis and re-thrombosis remain frequent in AV fistulas and AV
      grafts in haemodialysis patients despite stent-graft deployment. Re-stenosis of
      the deployed stent-graft is, only in the minority of the cases, responsible for
      AV access dysfunction.

PMID- 25373799
TI  - Flat-panel cone-beam CT-guided radiofrequency ablation of very small (<= 1.5 cm)
      liver tumors: technical note on a preliminary experience.
AB  - PURPOSE: The aim of the present study was to investigate the technical
      feasibility of flat-panel cone-beam CT (CBCT)-guided radiofrequency ablation
      (RFA) of very small (<1.5 cm) liver tumors. MATERIALS AND METHODS: Patients
      included were candidates for hepatic percutaneous RFA as they had single biopsy
      proven hepatic tumors sized <= 1.5 cm and poorly defined on ultrasonography.
      Following apnea induction, unenhanced CBCT scans were acquired and used to deploy
      the RF electrode with the aid of a virtual navigation system. If the tumor was
      not clearly identified on the unenhanced CBCT scan, a right retrograde arterial
      femoral access was established to carry out hepatic angiography and localize the
      tumor. Patients' lesions and procedural variables were recorded and analyzed.
      RESULTS: Three patients (2 male and 1 female), aged 68, 76, and 87 years were
      included; 3 lesions (2 hepato-cellular carcinoma and 1 metastasis from colorectal
      cancer) were treated. One patient required hepatic angiography. Cycles of apnea
      used to acquire CBCT images and to deploy the electrode lasted <120 s. Mean
      fluoroscopic time needed to deploy the electrode was 36.6 +/- 5.7 min. Mean
      overall procedural time was 66.0 +/- 22.9 min. No peri- or post-procedural
      complications were noted. No cases of incomplete ablation were noted at 1-month
      follow-up. CONCLUSION: Percutaneous CBCT-guided liver RFA with or without
      arterial hepatic angiography is technically feasible.

PMID- 25373800
TI  - Ebola and the Journal's response to "the most severe acute health emergency seen
      in modern times".

PMID- 25373801
TI  - Ebola virus disease: an update for anesthesiologists and intensivists.
AB  - PURPOSE: Ebola virus disease (EVD) is a viral hemorrhagic fever that is highly
      transmissible and all too often rapidly fatal. Recent outbreaks in West Africa
      reveal that this infection has the potential to be transmitted worldwide.
      Anesthesiologists and intensivists, due to their training in the management of
      the critically ill, may be called upon to assist in the management of these
      patients. The focus of this brief review is on the epidemiology, pathogenesis,
      and management of patients with EVD. SOURCE: Review of the current literature.
      PRINCIPAL FINDINGS: Ebola virus disease causes severe diarrhea, electrolyte
      disturbances and other major end-organ dysfunction. Early aggressive
      resuscitation may reduce the mortality of this disease. There is presently no
      available vaccine nor cure, with experimental therapies having yielded limited
      success. Personal protective equipment (PPE) is necessary for all patient
      contact, and enhanced PPE is required for all aerosol-generating medical
      procedures. CONCLUSION: Anesthesiologists and intensivists may be called upon to
      manage patients with EVD. It is important that these clinicians have an
      appreciation for the epidemiology and pathogenesis of this disease and for the
      proper utilization of PPE when treating these patients.

PMID- 25373803
TI  - Safety of early pharmacological thromboprophylaxis after subarachnoid hemorrhage.
AB  - OBJECTIVE: The recent guidelines on management of aneurysmal subarachnoid
      hemorrhage (aSAH) advise pharmacological thromboprophylaxis (PTP) after aneurysm
      obliteration. However, no study has addressed the safety of PTP in the aSAH
      population. Therefore, the aim of this study was to assess the safety of early
      PTP after aSAH. METHODS: Retrospective cohort of aSAH patients admitted between
      January 2012 and June 2013 in a single high-volume aSAH center. Traumatic SAH and
      perimesencephalic hemorrhage patients were excluded. Patients were grouped
      according to PTP timing: early PTP group (PTP within 24 hours of aneurysm
      treatment), and delayed PTP group (PTP started > 24 hours). RESULTS: A total of
      174 SAH patients (mean age 56.3+/-12.5 years) were admitted during the study
      period. Thirty-nine patients (22%) did not receive PTP, whereas 135 patients
      (78%) received PTP after aneurysm treatment or negative angiography. Among the
      patients who received PTP, 65 (48%) had an external ventricular drain. Twenty
      eight patients (21%) received early PTP, and 107 (79%) received delayed PTP. No
      patient in the early treatment group and three patients in the delayed PTP group
      developed an intracerebral hemorrhagic complication. Two required neurosurgical
      intervention and one died. These three patients were on concomitant PTP and dual
      antiplatelet therapy. CONCLUSIONS: The initiation of PTP within 24 hours may be
      safe after the treatment of a ruptured aneurysm or in angiogram-negative SAH
      patients with diffuse aneurysmal hemorrhage pattern. We suggest caution with
      concomitant use of PTP and dual antiplatelet agents, because it possibly
      increases the risk for intracerebral hemorrhage.

PMID- 25373804
TI  - Adherence to guidelines: experience of a canadian stroke prevention clinic.
AB  - BACKGROUND: Few studies have assessed the performance of stroke prevention
      clinics. In particular, limited information exists on patient compliance,
      achievement of therapeutic targets, and related occurrence of vascular events.
      METHODS: We compared our clinical practice to recommendations from published
      guidelines in newly referred patients for transient ischemic attack (TIA) or
      ischemic stroke between 2008 and 2010. We monitored our cohort for at least 1
      year and assessed for adequacy of vascular risk factor management, drug
      adherence, and occurrence of nonlethal vascular outcomes. RESULTS: Of 408
      patients, 57.8% had a stroke and 42.2% a TIA. The mean age was 68+/-13 years, and
      52% male. Average follow-up was 15.8 months. During follow-up, 253 patients
      (70.3%) completely achieved their blood pressure target, 151 (45.5%) achieved
      their low-density lipoprotein (LDL) cholesterol target, and 407 (99.8%) were on
      antithrombotics. Eighty-nine patients (21.8%) attained optimal therapy status,
      defined as reaching targets for LDL cholesterol, blood pressure, and
      antithrombotic use. Adherence to drug therapy was associated with attainment of
      optimal therapy status (p=0.01). Diabetes was associated with lower probability
      of attaining optimal therapy status (odds ratio [OR], 0.36; 95% confidence
      interval [CI], 0.20-0.66) and blood pressure targets (OR, 0.09; 95% CI, 0.05
      0.17). During follow-up, 52 (12.7%) patients had a nonlethal vascular event.
      CONCLUSION: Our study shows good attainment of therapeutic goals associated with
      adherence to drug therapy. However, optimal therapy status and blood pressure
      targets were more difficult to attain in patients with diabetes; therefore, more
      intensive preventive efforts may be required for these individuals.

PMID- 25373805
TI  - Misdiagnosis of cerebellar infarctions.
AB  - BACKGROUND: This retrospective study addresses for the first time the differences
      in clinical features and outcomes between those individuals with a cerebellar
      infarct who were correctly diagnosed on initial presentation compared to those
      who experienced delayed diagnosis. METHODS: A retrospective review was conducted
      of our stroke registry from 09/2003 to 02/2011. Forty seven patients had an
      isolated cerebellar infarction confirmed by MRI. Misdiagnosis was defined as the
      diagnosis given by the first physician. RESULTS: Among 47 patients identified,
      59.6% had delayed diagnosis. Five patients in the correct diagnosis group
      received intravenous tissue plasminogen activator, compared to none in the
      delayed diagnosis group. Complaints of weakness were protective from delayed
      diagnosis (OR 0.087, 95% CI 0.019-0.393, p=0.001). Conclusion : Patients with an
      isolated cerebellar infarction need to be considered when patients present with
      acute non-specific symptoms. Critical components of the neurological examination
      are omitted which are imperative to diagnose cerebellar infarcts. A thorough
      neurological examination may increase clinical suspicion of an ischemic stroke.

PMID- 25373806
TI  - Incidence, morbidity, and mortality of Terson syndrome in Hamilton, Ontario.
AB  - OBJECTIVE: Evaluate the incidence, neurologic morbidity, and mortality of
      patients with Terson syndrome. METHODS: Consecutive patients admitted to the
      Hamilton General Hospital from May 2012 to May 2013 with a diagnosis of
      spontaneous subarachnoid hemorrhage (SAH) were recruited. Funduscopic
      examinations were performed under pharmacological mydriasis. Outcome measures
      included: (1) the presence or absence of Terson syndrome; (2) The Glasgow Coma
      Scale (GCS), Hunt and Hess scale (H&H), and SAH Fisher score upon admission to
      the hospital; (3) the modified Rankin score upon discharge; and (4) and all-cause
      mortality. RESULTS: Forty-six patients were included and 10 had Terson syndrome
      (21%). The median H&H, GCS, and Fisher scores were 4, 6.5, and 4.0 for patients
      with Terson syndrome vs. 2, 14, and 3 for patients without Terson syndrome
      (p=0.0032, 0.0052, and 0.031), respectively. The median Rankin score was 6 for
      patients with Terson syndrome vs. 3.5 for patients without Terson syndrome
      (p=0.0019). The odds of all-cause mortality with Terson syndrome vs. no Terson
      syndrome was 12: 1 (95% confidence interval 2.33-61.7), p =0.003. Only four of
      the 10 patients with Terson syndrome survived. CONCLUSIONS: Based on this study,
      approximately one-fifth of patients admitted to the hospital with a spontaneous
      SAH could have Terson syndrome. Patients with Terson syndrome have significantly
      worse GCS and H&H scores upon admission to the hospital, lower modified Rankin
      scores upon discharge, and greater mortality. Thus, Terson syndrome is not rare
      among patients with SAH and carries a worse prognosis.

PMID- 25373807
TI  - Cerebral microbleeds and functional outcomes after ischemic stroke.
AB  - BACKGROUND: Whether an association exists between cerebral microbleeds (CMBs) and
      functional recovery after ischemic stroke is unclear. We aimed to evaluate the
      association between CMBs and functional outcome after acute ischemic stroke.
      METHODS: Consecutive patients with acute stroke were enrolled, and all patients
      were stratified into good and poor functional outcome groups at discharge and 6
      months after ischemic stroke by using a modified Rankin Scale score.
      Cardiovascular risk factors, CMBs, and white matter hyperintensities were
      compared between these two outcome groups. Logistic regression analysis was used
      to estimate the risk of poor functional outcomes. RESULTS: A total of 225
      patients were enrolled, 121 of whom were classified as having a good functional
      outcome at discharge and 142 as having a good 6-month functional outcome. The
      presence of CMBs was associated with a poor functional outcome at discharge [CMBs
      (+) patients in poor vs. good functional group; 48.1% vs. 30.6%; p=0.007] and 6
      months [53.0% vs. 30.3%; p=0.001]. After adjustment for confounding factors, only
      the presence of infratentorial CMBs was associated with a poor functional outcome
      at discharge and 6 months. The poor functional outcome group had more CMBs than
      the good outcome group at 6 months. CONCLUSIONS: Infratentorial cerebral
      microbleeds were significantly associated with worse functional outcomes not only
      in the early phase of ischemic stroke but also in the chronic phase. These
      findings suggest that the presence of infratentorial CMBs can predict poor
      functional outcome after acute ischemic stroke.

PMID- 25373808
TI  - Blood conservation in neurosurgery: erythropoietin and autologous donation.
AB  - BACKGROUND: Neurosurgery may involve significant blood loss and frequently
      requires allogeneic red blood cell (RBC) transfusion. Preoperative recombinant
      erythropoietin (EPO) may be used to improve erythroid status and recovery, and
      used either alone or in combination with preoperative autologous donation (PAD)
      it may reduce exposure to allogeneic RBC. We wished to study the use of EPO with
      and without PAD and the risk of RBC transfusion in neurosurgery. METHODS: Using a
      retrospective case-control design, 57 patients who received EPO preoperatively
      were matched 2:1 for age, sex, year of surgery, and International Classification
      of Diseases code most responsible for surgery (three were excluded because of
      stringent matching criteria, leaving 54 cases and 108 comparison subjects).
      Thirty-two cases participated in PAD. Medical and anesthetic records as well as
      laboratory investigations were reviewed and extracted. RESULTS: Allogeneic RBC
      exposure was identical for EPO cases and comparison subjects (18.5%). Concomitant
      PAD and EPO did not reduce allogeneic RBC exposure (21.9%), and resulted in a
      greater number of RBC units transfused. Last recorded hemoglobin levels suggested
      that autologous RBCs were not more liberally used. Patients who engaged in PAD
      and EPO suffered from iatrogenic anemia. A significant proportion (58.6%) of the
      autologous RBCs was ultimately not used and discarded. CONCLUSION: Further
      research is needed to determine the efficacy of EPO in neurological surgery. PAD
      does not appear to reduce the risk of allogeneic RBC transfusion, despite
      concomitant EPO. Indeed, PAD resulted in iatrogenic anemia and increased
      transfusion requirements. The cost-effectiveness of blood conservation efforts in
      neurosurgery deserves additional research.

PMID- 25373810
TI  - Nonmotor Symptoms and Cognitive Decline in de novo Parkinson's Disease.
AB  - BACKGROUND: Cognitive impairments are common in Parkinson's disease (PD). Despite
      its clinical importance, the development of dementia is still difficult to
      predict. In this study, we investigated the possible associations between non
      motor symptoms and the risk of developing dementia within a 2-year observation
      period in PD. METHODS: A total of 80 patients with PD participated in this study.
      Nonmotor symptoms (the Nonmotor Symptoms Questionnaire), PD status (Unified
      Parkinson's Disease Rating Scale), depression (Geriatric d Depression Scale or
      Montgomery-Asberg Depression Scale), stereopsis and severity of nonmotor symptoms
      (Non-motor symptoms scale) were assessed. Global cognitive function (Mini-Mental
      State Examination) were evaluated at baseline and 2 years later. RESULTS:
      Presence of depression, vivid dreaming, REM sleep behavior disorders, hyposmia,
      abnormal stereopsis, non-smoking and postural instability/ gait disturbance
      phenotype were associated with a significantly more rapid decline of Mini-Mental
      State Examination. Logistic regression analyses demonstrated that depression
      (odds ratio=13.895), abnormal stereopsis (odds ratio=10.729), vivid dreaming
      (odds ratio=4.16), REM sleep behavior disorders (odds ratio=5.353) and hyposmia
      (odds ratio=4.911) were significant independent predictors of dementia risk
      within 2 years. Postural instability/ gait disturbance phenotype and age >62
      years were also independent predictors of dementia risk (odd ratio=38.333, odds
      ratio=10.625). CONCLUSIONS: We suggest that depression, vivid dreaming, REM sleep
      behavior disorders, hyposmia and abnormal stereopsis are closely associated with
      cognitive decline, and that presence of these nonmotor symptoms predict the
      subsequent development of Parkinson's disease dementia.

PMID- 25373811
TI  - Pregabalin for the management of cervicogenic headache: a double blind study.
AB  - OBJECTIVES: The primary objective was to evaluate the effects of pregabalin
      relative to placebo in patients with chronic unilateral cervicogenic headache.
      Primary and secondary end points: To assess the change from baseline in the
      frequency of cervicogenic headache days per 28-day period between placebo and
      treatment group. To assess the change from baseline in the intensity of headache,
      and health outcome measures. STUDY DESIGN: This was a double-blind, randomized,
      placebo-controlled, parallel-group study, evaluating the efficacy and safety of
      pregabalin in patients with cervicogenic headache. PROCEDURES: The study
      consisted of two phases. A baseline of -28 days and a double-blind placebo
      controlled phase: with an escalation and maintenance phase, during which patients
      remained at their highest dose until the end of the study, at Day 86. RESULTS:
      Forty one patients were randomized, predominantly females, with a mean age of 52
      years old. At screening, both groups had, on average, 26 headache-days per month.
      By the final phase of the study, the number of headache days dropped to 16 per
      month for the pregabalin group while remaining stable for the placebo group
      (p=0.037). No serious adverse events were reported during the study. CONCLUSION:
      In this study, primary objectives were achieved with a statistically significant
      change of ten days in frequency of headache days; with minor side effects that
      were well tolerated.

PMID- 25373812
TI  - Algorithm for Quantifying Frontal EMG Responsiveness for Sedation Monitoring.
AB  - INTRODUCTION: To study stimulation-related facial electromyographic (FEMG)
      activity in intensive care unit (ICU) patients, develop an algorithm for
      quantifying the FEMG activity, and to optimize the algorithm for monitoring the
      sedation state of ICU patients. METHODS: First, the characteristics of FEMG
      response patterns related to vocal stimulation of 17 ICU patients were studied.
      Second, we collected continuous FEMG data from 30 ICU patients. Based on these
      data, we developed the Responsiveness Index (RI) algorithm that quantifies FEMG
      responses. Third, we compared the RI values with clinical sedation level
      assessments and adjusted algorithm parameters for best performance. RESULTS: In
      patients who produced a clinically observed response to the vocal stimulus, the
      poststimulus FEMG power was 0.33 uV higher than the prestimulus power. In
      nonresponding patients, there was no difference. The sensitivity and specificity
      of the developed RI for detecting deep sedation in the subgroup with low
      probability of encephalopathy were 0.90 and 0.79, respectively. CONCLUSION:
      Consistent FEMG patterns were found related to standard stimulation of ICU
      patients. A simple and robust algorithm was developed and good correlation with
      clinical sedation scores achieved in the development data.

PMID- 25373813
TI  - Iterative Reconstruction for Head CT: Effects on Radiation Dose and Image
      Quality.
AB  - BACKGROUND: Iterative reconstruction has been reported to reduce radiation dose
      in CT, while preserving and even improving image quality. The purpose of this
      study was to evaluate the effects of sinogram-affirmed iterative reconstruction
      (SAFIRE) on radiation dose reduction and image quality for noncontrast adult head
      CT and to compare SAFIRE with conventional filtered back-projection (FBP)
      reconstruction. METHODS: Institutional review board approval was obtained for
      this retrospective analysis of head CT scans reconstructed with SAFIRE and/or FBP
      for 107 patients. Radiation dose parameters were recorded from scanner-generated
      CT dose reports. Signal-to-noise and contrast-to-noise ratios (SNR, CNR) were
      calculated from gray and white matter (GM, WM) attenuation measurements. Image
      noise, artifacts, GM-WM differentiation, small structure visibility, and
      sharpness were graded by two readers. Statistical analysis included the
      independent-samples t test for quantitative data, the related samples Wilcoxon
      signed-rank test for qualitative data, the coefficient of repeatability for
      intraobserver variation, and kappa statistics for interobserver agreement.
      RESULTS: Mean effective dose was significantly reduced with SAFIRE from 2.0 to
      1.7 mSv (p<0.0001). SAFIRE also significantly improved GM SNR, WM SNR, and GM-WM
      CNR (p<0.0001). Significant reductions in image noise and posterior fossa
      artifact as well as improvements in GM-WM differentiation, small structure
      visibility, and sharpness were noted with SAFIRE (P<0.005). CONCLUSIONS: SAFIRE
      for noncontrast adult head CT reduces patient radiation dose by 15% for the
      settings employed at our institution, while significantly improving multiple
      quantitative and qualitative measures of image quality.

PMID- 25373814
TI  - Case of multiple sulfatase deficiency and ocular albinism: a diagnostic odyssey.
AB  - BACKGROUND: Multiple sulfatase deficiency (MSD) is a rare autosomal recessive
      inborn error of lysosomal metabolism. The clinical phenotypic spectrum
      encompasses overlapping features of variable severity and is suggestive of
      individual single sulfatase deficiencies (i.e., metachromatic leukodystrophy,
      mucopolysaccharidosis, and X-linked ichthyosis). CASE REPORT: We describe a 3
      year-old male with severe hypotonia, developmental regression and progressive
      neurodegeneration, coarse facial features, nystagmus (from ocular albinism), and
      dysmyelinating motor sensory neuropathy. Ethics approval was obtained from the
      Western University Ontario. RESULTS: Extensive investigative work-up identified
      deficiencies of multiple sulfatases: heparan sulfate sulfamidase: 6.5
      nmoles/mg/protein/17 hour (reference 25.0-75.0), iduronate-2-sulfate sulfatase: 9
      nmol/mg/protein/4 hour (reference 31-110), and arylsulfatase A: 3.8 nmoles/hr/mg
      protein (reference 22-50). The identification of compound heterozygous pathogenic
      mutations in the SUMF1 gene c.836 C>T (p.A279V) and c.1045C>T (p.R349W) confirmed
      the diagnosis of MSD. CONCLUSION: The complex clinical manifestations of MSD and
      the unrelated coexistence of ocular albinism as in our case can delay diagnosis.
      Genetic counselling should be provided to all affected families.

PMID- 25373815
TI  - Eosinophil infiltrates in pilocytic astrocytomas of children and young adults.
AB  - OBJECTIVE: Eosinophils may affect each stage of tumour development. Many studies
      have suggested that tumour-associated tissue eosinophilia (TATE) is associated
      with favourable prognosis in some malignant tumours. However, only a few studies
      exist on TATE in central nervous system (CNS) tumours. Our recent study exhibited
      eosinophils in atypical teratoid/rhabdoid tumours (AT/RTs), pediatric malignant
      CNS tumours with divergent differentiation. This study examines eosinophils in
      pilocytic astrocytomas (PAs). METHODS: The study included 44 consecutive cases of
      patients with PAs and no concurrent CNS inflammatory disease. RESULTS: We found
      eosinophils in 19 (43%) of 44 PAs (patient age range, 0.5-72 years). Eosinophils
      were intratumoural and clearly distinguishable. The density of eosinophils was
      rare to focally scattered. PAs containing eosinophils were located throughout the
      CNS. Furthermore, eosinophilic infiltration was identified in 18 (62%) of 29
      pediatric (age range, 0.5-18 years) PAs but only 1 (7%) of 15 (p<0.001,
      significantly less) adult (age range, 20-72 years) PAs. Eosinophilic infiltration
      showed no significant differences between PAs with and without MRI cystic
      formation, surgical procedures, or PAs with and without leptomeningeal
      infiltration. In comparison, eosinophils were absent in 10 pediatric (age range,
      0.5-15 years) ependymomas (or anaplastic ependymomas). CONCLUSIONS: These results
      suggest that eosinophils are common in pediatric PAs but rare in adult PAs. This
      difference is probably related to the developing immune system and different
      tumour-specific antigens in children. TATE may play a functional role in the
      development of pediatric PAs, as well as some other pediatric CNS tumours such as
      AT/RTs.

PMID- 25373816
TI  - Statin-associated Autoimmune Myopathies: A Pathophysiologic Spectrum.
AB  - BACKGROUND: Statins have recently been reported to cause a rare autoimmune
      inflammatory and/or necrotic myopathy that begins or persists after drug
      cessation. METHODS: We report on 26 patients seen at a neuromuscular centre
      between 2005 and 2011 who demonstrated muscle weakness/myalgias and creatine
      kinase elevations during or after statin treatment with continuation of signs and
      symptoms despite statin withdrawal. RESULTS: All patients were treated with
      immunosuppressive therapy with good response; all improved biochemically and 86%
      improved clinically. Sixty-five percent of patients who attempted to taper off
      immunosuppressive therapy relapsed. We report on a novel finding whereby five of
      the seven patients who underwent multiple biopsies throughout their disease
      demonstrated a transformation of their histological diagnosis, with four
      progressing from having myofibre necrosis with minimal or no inflammation to a
      diagnosis of polymyositis. CONCLUSIONS: This study offers preliminary evidence
      that statin-associated necrotizing myopathy and statin-associated polymyositis
      may not be separate entities but are part of the same pathophysiological
      spectrum. Both entities respond well to immunosuppression.

PMID- 25373817
TI  - Alzheimer's disease: initial clinical implementation of automated volumetry.

PMID- 25373818
TI  - Upside-down Drawing in Posterior Cortical Atrophy.

PMID- 25373819
TI  - 4D Flow Preliminary Investigation for Anterior Fossa Dural Arteriovenous Fistula.

PMID- 25373820
TI  - Recanalization of intracranial carotid artery occlusion associated with jugular
      vein cannulation.

PMID- 25373821
TI  - Cerebral Microbleed Causing an Acute Stroke-like Episode in a CADASIL Patient.

PMID- 25373822
TI  - Striatum inhibition: clues for cocaine addiction therapy.

PMID- 25373823
TI  - Friedreich's Ataxia Presenting as Isolated Spastic Paraparesis.

PMID- 25373824
TI  - Development of LGI1 antibody encephalitis after treatment of lung cancer.

PMID- 25373825
TI  - Nitrous Oxide (N2O)-Induced Acute Psychosis.

PMID- 25373826
TI  - Gold-promoted structurally ordered intermetallic palladium cobalt nanoparticles
      for the oxygen reduction reaction.
AB  - Considerable efforts to make palladium and palladium alloys active catalysts and
      a possible replacement for platinum have had a marginal success. Here we report
      on a structurally ordered Au10Pd40Co50 catalyst that exhibits comparable activity
      to conventional platinum catalysts in both acid and alkaline media. Electron
      microscopic techniques demonstrate that, at elevated temperatures, palladium
      cobalt nanoparticles undergo an atomic structural transition from core-shell to a
      rare intermetallic ordered structure with twin boundaries forming stable {111},
      {110} and {100} facets via addition of gold atoms. The superior stability of this
      catalyst compared with platinum after 10,000 potential cycles in alkaline media
      is attributed to the atomic structural order of PdCo nanoparticles along with
      protective effect of clusters of gold atoms on the surface. This strategy of
      making ordered palladium intermetallic alloy nanoparticles can be used in diverse
      heterogeneous catalysis where particle size and structural stability matter.

PMID- 25373827
TI  - Food web efficiency differs between humic and clear water lake communities in
      response to nutrients and light.
AB  - This study demonstrates that clear and humic freshwater pelagic communities
      respond differently to the same environmental stressors, i.e. nutrient and light
      availability. Thus, effects on humic communities cannot be generalized from
      existing knowledge about these environmental stressors on clear water
      communities. Small humic lakes are the most numerous type of lake in the boreal
      zone, but little is known about how these lakes will respond to increased inflows
      of nutrients and terrestrial dissolved organic C (t-DOC) due to climate change
      and increased human impacts. Therefore, we compared the effects of nutrient
      addition and light availability on pelagic humic and clear water lake communities
      in a mesocosm experiment. When nutrients were added, phytoplankton production
      (PPr) increased in both communities, but pelagic energy mobilization (PEM) and
      bacterial production (BP) only increased in the humic community. At low light
      conditions, the addition of nutrients led to increased PPr only in the humic
      community, suggesting that, in contrast to the clear water community, humic
      phytoplankton were already adapted to lower ambient light levels. Low light
      significantly reduced PPr and PEM in the clear water community, but without
      reducing total zooplankton production, which resulted in a doubling of food web
      efficiency (FWE = total zooplankton production/PEM). However, total zooplankton
      production was not correlated with PEM, PPr, BP, PPr:BP or C:nutrient
      stoichiometry for either community type. Therefore, other factors such as food
      chain length, food quality, ultra-violet radiation or duration of the experiment,
      must have determined total zooplankton production and ultimately FWE.

PMID- 25373828
TI  - Neoadjuvant bevacizumab and chemoradiotherapy in locally advanced rectal cancer:
      early outcome and technical impact on toxicity.
AB  - BACKGROUND: We aimed to evaluate early clinical and pathological results for
      treating locally advanced rectal cancer with bevacizumab and neoadjuvant
      concurrent chemoradiotherapy using the technique of prone-position volumetric
      modulated arc therapy and to compare the toxicity of volumetric modulated arc
      therapy with that of supine-position four-field box radiotherapy. METHODS: Twelve
      patients with stage IIA to IVA rectal adenocarcinoma, treated with neoadjuvant
      concurrent chemoradiotherapy (45 Gy in 25 fractions to the rectal tumor and
      pelvic lymphatics) and bevacizumab, were prospectively enrolled. Chemotherapy
      included FOLFOX (leucovorin, fluorouracil, and oxaliplatin) (n=11) and 5
      fluorouracil (n=1). All patients received prone-position volumetric modulated arc
      therapy. A historical cohort treated with supine-position box radiotherapy,
      including six other patients treated with bevacizumab-based concurrent
      chemoradiotherapy in our hospital, was used for comparison. Setup errors,
      toxicities, and potential biomarkers were evaluated. RESULTS: All patients
      completed neoadjuvant concurrent chemoradiotherapy and underwent total mesorectal
      excision. Four (33.3%) patients had pathological complete response. Significantly
      more grade 2 or 3 diarrhea was associated with the supine-box technique (5/6
      versus 2/12, P=0.01). The magnitude of setup errors was similar between the
      supine-box and prone volumetric modulated arc therapy techniques. The estimated 2
      year survival and 2-year failure-free survival rates were 100% and 72.9% in the
      prone volumetric modulated arc therapy group and 66.7% and 66.7% in the supine
      box group, respectively. CONCLUSIONS: The early clinical outcome has been
      encouraging. Volumetric modulated arc therapy in prone-positioned patients was
      technically advantageous and reduced bowel toxicity.

PMID- 25373829
TI  - Computational modeling of nanoscale and microscale particle deposition, retention
      and dosimetry in the mouse respiratory tract.
AB  - Comparing effects of inhaled particles across rodent test systems and between
      rodent test systems and humans is a key obstacle to the interpretation of common
      toxicological test systems for human risk assessment. These comparisons,
      correlation with effects and prediction of effects, are best conducted using
      measures of tissue dose in the respiratory tract. Differences in lung geometry,
      physiology and the characteristics of ventilation can give rise to differences in
      the regional deposition of particles in the lung in these species. Differences in
      regional lung tissue doses cannot currently be measured experimentally. Regional
      lung tissue dosimetry can however be predicted using models developed for rats,
      monkeys, and humans. A computational model of particle respiratory tract
      deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a
      cross-species suite of available models for particle dosimetry in the lung.
      Airflow and particle transport equations were solved throughout the respiratory
      tract of these mice strains to obtain temporal and spatial concentration of
      inhaled particles from which deposition fractions were determined. Particle
      inhalability (Inhalable fraction, IF) and upper respiratory tract (URT)
      deposition were directly related to particle diffusive and inertial properties.
      Measurements of the retained mass at several post-exposure times following
      exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and
      nanoscale silver particles were used to calibrate and verify model predictions of
      total lung dose. Interstrain (mice) and interspecies (mouse, rat and human)
      differences in particle inhalability, fractional deposition and tissue dosimetry
      are described for ultrafine, fine and coarse particles.

PMID- 25373830
TI  - Health effects after firing small arms comparing leaded and unleaded ammunition.
AB  - A number of Norwegian soldiers have reported health problems after live-fire
      training using the HK416 rifle. The objective of this study was to characterize
      gaseous and particulate emissions from three different types of ammunition, and
      record the health effects after exposure to emissions from live-firing. Fifty
      five healthy, non-smoking men (mean age 40 years) were recruited and divided
      randomly into three groups, one for each type of ammunition. All subjects fired
      the HK416 rifle in a semi-airtight tent for 60 min using leaded ammunition,
      unleaded ammunition and modified unleaded ammunition. Gaseous and particulate
      emissions were monitored within the tent. The symptoms experienced by the
      subjects were recorded immediately after and the day after firing using a
      standardized questionnaire. The concentrations of particulate matter and copper
      exceeded their respective occupational exposure limits (eight hours per day, five
      days a week) by a factor of 3 and 27, respectively. Of the 55 subjects, 54
      reported general and respiratory symptoms. The total number of symptoms reported
      was significantly higher among shooters using unleaded ammunition as compared
      with the use of leaded and modified unleaded ammunition. Copper was the substance
      that had the highest concentration relative to its toxicity. Although the general
      symptoms were found to be consistent with the development of metal fume fever,
      the respiratory symptoms indicated an irritant effect of the airways different
      from that seen in metal fume fever. More symptoms were reported when unleaded
      ammunition was used compared with leaded and modified unleaded ammunition.

PMID- 25373831
TI  - Documented lifestyle education among young adults with incident hypertension.
AB  - BACKGROUND: Only 38% of young adults with hypertension have controlled blood
      pressure. Lifestyle education is a critical initial step for hypertension
      control. Previous studies have not assessed the type and frequency of lifestyle
      education in young adults with incident hypertension. OBJECTIVE: The purpose of
      this study was to determine patient, provider, and visit predictors of documented
      lifestyle education among young adults with incident hypertension. DESIGN: We
      conducted a retrospective analysis of manually abstracted electronic health
      record data. PARTICIPANTS: A random selection of adults 18-39 years old (n =
      500), managed by a large academic practice from 2008 to 2011 and who met JNC 7
      clinical criteria for incident hypertension, participated in the study. MAIN
      MEASURES: The primary outcome was the presence of any documented lifestyle
      education during one year after meeting criteria for incident hypertension.
      Abstracted topics included documented patient education for exercise, tobacco
      cessation, alcohol use, stress management/stress reduction, Dietary Approaches to
      Stop Hypertension (DASH) diet, and weight loss. Clinic visits were categorized
      based upon a modified established taxonomy to characterize patients' patterns of
      outpatient service. We excluded patients with previous hypertension diagnoses,
      previous antihypertensive medications, or pregnancy. Logistic regression was used
      to identify predictors of documented education. KEY RESULTS: Overall, 55% (n =
      275) of patients had documented lifestyle education within one year of incident
      hypertension. Exercise was the most frequent topic (64%). Young adult males had
      significantly decreased odds of receiving documented education. Patients with a
      previous diagnosis of hyperlipidemia or a family history of hypertension or
      coronary artery disease had increased odds of documented education. Among visit
      types, chronic disease visits predicted documented lifestyle education, but not
      acute or other/preventive visits. CONCLUSIONS: Among young adults with incident
      hypertension, only 55% had documented lifestyle education within one year.
      Knowledge of patient, provider, and visit predictors of education can help better
      target the development of interventions to improve young adult health education
      and hypertension control.

PMID- 25373832
TI  - Choosing wisely: prevalence and correlates of low-value health care services in
      the United States.
AB  - BACKGROUND: Specialty societies in the United States identified low-value tests
      and procedures that contribute to waste and poor health care quality via
      implementation of the American Board of Internal Medicine Foundation's Choosing
      Wisely initiative. OBJECTIVE: To develop claims-based algorithms, to use them to
      estimate the prevalence of select Choosing Wisely services and to examine the
      demographic, health and health care system correlates of low-value care at a
      regional level. DESIGN: Using Medicare data from 2006 to 2011, we created claims
      based algorithms to measure the prevalence of 11 Choosing Wisely-identified low
      value services and examined geographic variation across hospital referral regions
      (HRRs). We created a composite low-value care score for each HRR and used linear
      regression to identify regional characteristics associated with more intense use
      of low-value services. PATIENTS: Fee-for-service Medicare beneficiaries over age
      65. MAIN MEASURES: Prevalence of selected Choosing Wisely low-value services. KEY
      RESULTS: The national average annual prevalence of the selected Choosing Wisely
      low-value services ranged from 1.2% (upper urinary tract imaging in men with
      benign prostatic hyperplasia) to 46.5% (preoperative cardiac testing for low
      risk, non-cardiac procedures). Prevalence across HRRs varied significantly.
      Regional characteristics associated with higher use of low-value services
      included greater overall per capita spending, a higher specialist to primary care
      ratio and higher proportion of minority beneficiaries. CONCLUSIONS: Identifying
      and measuring low-value health services is a prerequisite for improving quality
      and eliminating waste. Our findings suggest that the delivery of wasteful and
      potentially harmful services may be a fruitful area for further research and
      policy intervention for HRRs with higher per-capita spending. These findings
      should inform action by physicians, health systems, policymakers, payers and
      consumer educators to improve the value of health care by targeting services and
      areas with greater use of potentially inappropriate care.

PMID- 25373833
TI  - Hormone therapy use in women veterans accessing veterans health administration
      care: a national cross-sectional study.
AB  - The majority of women Veterans using VA (Veterans Administration) care fall in
      the 45-65 year-old age range. Understanding how menopause is managed in this
      group is of importance to optimizing their health. OBJECTIVE: National population
      estimates showed a prevalence of hormone therapy (HT) use by women over 45 years
      of 4.7 % (2009-2010). Our study described the frequency of HT use among women
      Veterans in VA, and examined whether mental health (MH) was predictive of HT use.
      DESIGN: This was a cross-sectional analysis of national VA administrative data
      for fiscal year 2009. PARTICIPANTS: Women Veterans over the age of 45 (N =
      157,195) accessing VA outpatient care were included in the analysis. MAIN
      MEASURES: Logistic regression analyses using HT use as the dependent variable.
      KEY RESULTS: Mean age was 59.4 years (SD =12.2, range =46-110), and 16,227 (10.3
      %) of all women used HT. Hysterectomy (OR 3.99 [3.53, 4.49]) and osteoporosis
      (1.34 [1.27, 1.42]) were the strongest medical indicators of HT use. A total of
      49,557 (31.5 %) women in the sample received at least one primary diagnosis of a
      MH disorder and were more likely to use HT than women with no MH diagnoses
      (unadjusted OR 1.56, 95 % CI [1.50, 1.61]). Women Veterans with a mood disorder
      (depression/bipolar) or anxiety disorder [post-traumatic stress disorder (PTSD),
      other anxiety diagnoses] were more likely to use HT after controlling for
      demographics and medical comorbidity. CONCLUSION: The prevalence of HT use among
      women Veterans using VA is more than twice that of the general population. Prior
      work suggested that women Veterans were discontinuing HT at comparable rates, but
      these data demonstrate that decline in VA HT use has not kept pace with that of
      civilian medical care. The association of MH diagnosis with HT use suggests that
      MH plays an important role in VA rates. Further study is needed to understand
      contributing patient and provider factors.

PMID- 25373834
TI  - Clinicians' views and experiences of interventions to enhance the quality of
      antibiotic prescribing for acute respiratory tract infections.
AB  - BACKGROUND: Evidence shows a high rate of unnecessary antibiotic prescriptions in
      primary care in Europe and the United States. Given the costs of widespread use
      and associated antibiotic resistance, reducing inappropriate use is a public
      health priority. OBJECTIVE: We aimed to explore clinicians' experiences of
      training in communication skills and use of a patient booklet and/or a C-reactive
      protein (CRP) point-of-care test to reduce antibiotic prescribing for acute
      respiratory tract infections (RTIs). DESIGN: We used a qualitative research
      approach, interviewing clinicians who participated in a randomised controlled
      trial (RCT) testing two contrasting interventions. PARTICIPANTS: General practice
      clinicians in Belgium, England, The Netherlands, Poland, Spain and Wales
      participated in the study. APPROACH: Sixty-six semi-structured interviews were
      transcribed verbatim, translated into English where necessary, and analysed using
      thematic and framework analysis. KEY RESULTS: Clinicians from all countries
      attributed benefits for themselves and their patients to using both
      interventions. Clinicians reported that the communication skills training and use
      of the patient booklet gave them greater confidence in addressing patient
      expectations for an antibiotic by providing answers to common questions and
      supporting the clinician's own explanations. Clinicians felt the booklet could be
      used for a variety of patients and for different types of infections. The CRP
      test was viewed as a tool to decrease diagnostic uncertainty, to support non
      prescription decisions, and to reassure patients, but was only necessary when
      clinicians were uncertain about the need for antibiotics. CONCLUSION: Providing
      clinicians with training and support tools for use in practice was received
      positively and was valued by clinicians across countries. Interventions seemed to
      have influenced behaviour by increasing clinician knowledge about illness
      severity and prescribing, increasing confidence in making non-prescribing
      decisions when antibiotics were unnecessary, and enabling clinicians to
      anticipate positive outcomes when making such decisions. Addressing such
      determinants of behaviour change enabled interventions to be relevant for
      clinicians working across different contexts.

PMID- 25373835
TI  - Hospice use among nursing home and non-nursing home patients.
AB  - BACKGROUND: For nursing home patients, hospice use and associated costs have
      grown dramatically. A better understanding of hospice in all care settings,
      especially how patients move across settings, is needed to inform debates about
      appropriateness of use and potential policy reform. OBJECTIVE: Our aim was to
      describe characteristics and utilization of hospice among nursing home and non
      nursing home patients. DESIGN AND PARTICIPANTS: Medicare, Medicaid and Minimum
      Data Set data, 1999-2008, were merged for 3,771 hospice patients aged 65 years
      and above from a safety net health system. Patients were classified into four
      groups who received hospice: 1) only in nursing homes; 2) outside of nursing
      homes; 3) crossover patients utilizing hospice in both settings; and 4) "near
      transition" patients who received hospice within 30 days of a nursing home stay.
      MAIN MEASURES: Differences in demographics, hospice diagnoses and length of stay,
      utilization and costs are presented with descriptive statistics. KEY RESULTS:
      Nursing home hospice patients were older, and more likely to be women and to have
      dementia (p < 0.0001). Nearly one-third (32.3 %) of crossover patients had
      hospice stays > 6 months, compared with the other groups (16 % of nursing home
      hospice only, 10.7 % of non-nursing home hospice and 7.6 % of those with near
      transitions) (p < 0.0001). Overall, 27.7 % of patients had a hospice stay <1
      week, but there were marked differences between groups-48 % of near-transition
      patients vs. 7.4 % of crossover patients had these short hospice stays (p <
      0.0001). Crossover and near-transition hospice patients had higher costs to
      Medicare compared to other groups (p < 0.05). CONCLUSIONS: Dichotomizing hospice
      users only into nursing home vs. non-nursing home patients is difficult, due to
      transitions across settings. Hospice patients with transitions accrue higher
      costs. The impact of changes to the hospice benefit on patients who live or move
      through nursing homes near the end of life should be carefully considered.

PMID- 25373836
TI  - Impact of patient requests on provider-perceived visit difficulty in primary
      care.
AB  - BACKGROUND: "Difficult visits" are common in primary care and may contribute to
      primary care provider (PCP) career dissatisfaction and burnout. Patient requests
      occur in approximately half of primary care visits and may be a source of
      clinician-patient miscommunication or conflict, contributing to perceived visit
      difficulty. OBJECTIVE: We aimed to determine associations between types of
      patient requests and PCP-perceived visit difficulty. DESIGN: This was an
      observational study, nested in a multicenter randomized trial of depression
      engagement interventions. SUBJECTS: We included 824 patient visits within 135 PCP
      practices in Northern California occurring from June 2010 to March 2012. MAIN
      MEASURES: PCP-perceived visit difficulty was quantified using a three-item scale
      (relative visit difficulty, amount of effort required, and amount of time
      required; Cronbach's alpha = 0.81). Using linear regression, the difficulty scale
      (score range 0-2 from least to most difficult) was modeled as a function of:
      patient requests for diagnostics tests, pain medications, and specialist
      referrals; PCP perception of likely depression or likely substance abuse; patient
      sociodemographics, comorbidity, depression; PCP characteristics and practice
      setting. RESULTS: Patients requested diagnostic tests, pain medications, and
      specialist referrals in 37.2, 20.0 and 30.0 % of visits, respectively. After
      adjustment for patient medical and psychiatric complexity, perceived difficulty
      was significantly higher when patients requested diagnostic tests [parameter
      estimate (PE) 0.11, (95 % CI: 0.03, 0.20)] but not when patients requested pain
      medications [PE -0.04 (95 % CI: -0.15, 0.08)] or referrals [PE 0.04 (95 % CI: 
      0.07, 0.25)]. CONCLUSIONS: PCP-perceived visit difficulty is associated with
      patient requests for diagnostic tests, but not requests for pain medications or
      specialist referrals. In this era of "choosing wisely," PCPs may be challenged to
      respond to diagnostic test requests in an evidence-based manner, while
      maintaining the provider-patient relationship and PCP career satisfaction.

PMID- 25373837
TI  - Quality of life in bimodal hearing users (unilateral cochlear implants and
      contralateral hearing aids).
AB  - The main objective was to evaluate the bimodal self-rated benefits on auditory
      performance under real conditions and the quality of life in two groups of
      cochlear-implanted adults, with or without a contralateral hearing aid. The
      secondary objective was to investigate correlations between the use of a hearing
      aid and residual hearing on the non-implanted ear. This retrospective study was
      realized between 2000 and 2010 in two referral centers. A population of 183
      postlingually deaf adults, implanted with a cochlear experience superior to 6
      months, was selected. The Speech, Spatial, and other Qualities of Hearing Scale
      were administered to evaluate the auditory performances, and the Nijmegen
      Cochlear Implant Questionnaire to evaluate the quality of life. The population
      was divided into two groups: a group with unilateral cochlear implants (Cochlear
      Implant-alone, n = 54), and a bimodal group with a cochlear implant and a
      contralateral hearing aid (n = 62). Both groups were similar in terms of auditory
      deprivation duration, duration of cochlear implant use, and pure-tone average on
      the implanted ear. There was a significant difference in terms of pure-tone
      average on low and low-to-mid frequencies on the non-implanted ear. The scores on
      both questionnaires showed an improvement in the basic sound perception and
      quality of social activities for the bimodal group. The results suggest that the
      bimodal stimulation (cochlear implant and contralateral hearing aid) improved
      auditory perception in quiet and the quality of life domain of social activities.

PMID- 25373838
TI  - Automated and objective action coding of facial expressions in patients with
      acute facial palsy.
AB  - Aim of the present observational single center study was to objectively assess
      facial function in patients with idiopathic facial palsy with a new computer
      based system that automatically recognizes action units (AUs) defined by the
      Facial Action Coding System (FACS). Still photographs using posed facial
      expressions of 28 healthy subjects and of 299 patients with acute facial palsy
      were automatically analyzed for bilateral AU expression profiles. All palsies
      were graded with the House-Brackmann (HB) grading system and with the Stennert
      Index (SI). Changes of the AU profiles during follow-up were analyzed for 77
      patients. The initial HB grading of all patients was 3.3 +/- 1.2. SI at rest was
      1.86 +/- 1.3 and during motion 3.79 +/- 4.3. Healthy subjects showed a
      significant AU asymmetry score of 21 +/- 11 % and there was no significant
      difference to patients (p = 0.128). At initial examination of patients, the
      number of activated AUs was significantly lower on the paralyzed side than on the
      healthy side (p < 0.0001). The final examination for patients took place 4 +/- 6
      months post baseline. The number of activated AUs and the ratio between affected
      and healthy side increased significantly between baseline and final examination
      (both p < 0.0001). The asymmetry score decreased between baseline and final
      examination (p < 0.0001). The number of activated AUs on the healthy side did not
      change significantly (p = 0.779). Radical rethinking in facial grading is
      worthwhile: automated FACS delivers fast and objective global and regional data
      on facial motor function for use in clinical routine and clinical trials.

PMID- 25373840
TI  - Use of a tourniquet in total knee arthroplasty: a systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: A tourniquet is commonly used in total knee arthroplasty (TKA).
      However, the effectiveness and safety of tourniquets are debated. We performed
      this study to investigate whether patients benefit from the use of tourniquets in
      TKA. METHODS: The literature search was conducted using PubMed, Cochrane Library,
      MEDLINE, Embase, and other medical databases. After a literature search, 26
      randomized controlled trials involving 1,450 knees were analyzed. RESULTS:
      Tourniquet use significantly decreased intraoperative blood loss, transfusion
      rate, and operation time but not postoperative blood loss, measurable total blood
      loss, calculated total blood loss, transfusion volume, incidence of pulmonary
      embolism, or duration of hospital stay. It also slowed down joint functional
      recovery in the short term and increased the incidence of deep vein thrombosis
      and other minor wound complications. CONCLUSIONS: Data from this meta-analysis
      indicate that patients may benefit from the use of a tourniquet in TKA; however,
      it use is accompanied by disadvantages and complications. Because of the very low
      evidence quality and lower grading of recommendations, assessment, development,
      and evaluation recommendation strength, no guidelines can be developed based on
      current evidence.

PMID- 25373839
TI  - Response evaluation after chemoradiotherapy for advanced staged oropharyngeal
      squamous cell carcinoma: a nationwide survey in the Netherlands.
AB  - Following failure of chemoradiotherapy (CRT) for advanced staged oropharyngeal
      squamous cell carcinomas (OPSCC), residual tumor can often be treated
      successfully with salvage surgery, if detected early. Current clinical practice
      in the VU University Medical Center is to perform routine response evaluation,
      i.e., examination under general anesthesia (EUA), 12 weeks after treatment.
      However, in the Netherlands there is no consensus on response evaluation in
      patients with advanced oropharyngeal cancer. Questionnaire on current clinical
      practice concerning response evaluation after CRT for advanced OPSCC in all eight
      head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative
      Group. The response rate was 100%. Response evaluation was routinely performed
      with various methods in five institutions (62.5%) and in one institute (12.5%)
      only if clinical evaluation was difficult. Two centers (25%) did not perform
      response evaluation. In case of suspicion of residual disease during follow-up,
      six centers (75%) performed imaging prior to EUA and two centers (25%) only if
      clinical evaluation was difficult. Diagnostic techniques used prior to EUA were
      MRI (87.5%), diffusion-weighted MRI (37.5%), 18F-FDG-PET-CT (75-87.5%) and CT
      (37.5%). This survey shows a substantial variation in the diagnostic policy
      concerning response evaluation after CRT for advanced OPSCC in the Netherlands.
      There is a need for guidelines for response evaluation in patients with advanced
      oropharyngeal cancer.

PMID- 25373841
TI  - Streptomyces klenkii sp. nov., isolated from deep marine sediment.
AB  - A novel actinomycete strain, designated S2704(T), was isolated from a deep
      sediment sample, collected from the southern Black Sea coast, Turkey and
      characterized using a polyphasic approach. Comparison of 16S rRNA gene sequences
      showed that strain S2704(T) is a member of the genus Streptomyces, exhibiting
      highest similarity with Streptomyces specialis GW 41-1564(T) (97.1 %). Strain
      S2704(T) could be distinguished from all other Streptomyces species with validly
      published names by sequence similarity values less than 97.0 %. The isolate was
      found to contain LL-diaminopimelic acid as the diagnostic diamino acid. Whole
      cell hydrolysates were found to contain glucose, mannose and ribose. The polar
      lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylmethylethanolamine, phosphatidylinositol, glycophospholipid, a
      phospholipid and two unknown glycolipids. The predominant menaquinones were
      identified as MK-9(H8) and MK-10(H6). The major fatty acids were found to be
      anteiso-C17:0, iso-C16:0 and anteiso-C15:0. The G+C content of the DNA was
      determined to be 72.2 mol%. On the basis of its phenotypic and molecular
      properties, strain S2704(T) is considered to be a novel species of the genus
      Streptomyces, for which the name Streptomyces klenkii sp. nov. is proposed. The
      type strain is S2704(T) (=DSM 42104(T) = KCTC 29202(T)). 

PMID- 25373842
TI  - Filtered molasses concentrate from sugar cane: natural functional ingredient
      effective in lowering the glycaemic index and insulin response of high
      carbohydrate foods.
AB  - An aqueous filtered molasses concentrate (FMC) sourced from sugar cane was used
      as a functional ingredient in a range of carbohydrate-containing foods to reduce
      glycaemic response. When compared to untreated controls, postprandial glucose
      responses in the test products were reduced 5-20%, assessed by accredited
      glycaemic index (GI) testing. The reduction in glucose response in the test foods
      was dose-dependent and directly proportional to the ratio of FMC added to the
      amount of available carbohydrate in the test products. The insulin response to
      the foods was also reduced with FMC addition as compared to untreated controls.
      Inclusion of FMC in test foods did not replace any formulation ingredients; it
      was incorporated as an additional ingredient to existing formulations. Filtered
      molasses concentrate, made by a proprietary and patented process, contains many
      naturally occurring compounds. Some of the identified compounds are known to
      influence carbohydrate metabolism, and include phenolic compounds, minerals and
      organic acids. FMC, sourced from a by-product of sugar cane processing, shows
      potential as a natural functional ingredient capable of modifying carbohydrate
      metabolism and contributing to GI reduction of processed foods and beverages.

PMID- 25373843
TI  - Influence of culinary processing time on saffron's bioactive compounds (Crocus
      sativus L.).
AB  - Saffron, the dried stigmas of Crocus sativus L., is used as a condiment spice.
      The major bioactive compounds are crocins, picrocrocin and safranal, which are
      responsible for the sensory profile of saffron (color, flavor and aroma,
      respectively), and also health-promoting properties. In this paper, the effect on
      the bioactive compounds of different cooking times in boiling water at 100 
      degrees C in samples of Saffron from La Mancha (safranal, picrocrocin, trans
      crocin 4, cis-crocin 4 and trans-crocin 3) was investigated. Performance
      characteristics of High Performance Liquid Chromatography with Variable
      Wavelength Detector method, parameters of linearity, limits of detection and
      quantification are reported. High Performance Liquid Chromatography-Photo Diode
      Array-Mass Spectrometry was used as a confirmatory technique in crocins
      identification. When the samples are subjected to different cooking times, they
      present different behaviors, depending on the bioactive compound. In this way, no
      changes were observed in the concentration of picrocrocin, while heat culinary
      treatment adversely affects the concentrations of crocins and safranal.

PMID- 25373845
TI  - Size selected clusters and particles: from physical chemistry and chemical
      physics to catalysis.

PMID- 25373844
TI  - Effects of engineered conserved dopamine neurotrophic factor-expressing bone
      marrow stromal cells on dopaminergic neurons following 6-OHDA administrations.
AB  - Numerous lines of evidence previously indicated that conserved dopamine
      neurotrophic factor (CDNF) has potential therapeutic value for Parkinson's
      disease (PD); however, this hypothesis remains controversial. In the present
      study, the therapeutic effects of engineered CDNF-expressing bone marrow stromal
      cells (CDNF-BMSCs) on dopaminergic (DA) neurons were evaluated in vivo. CDNF
      BMSCs and control BMSCs were transplanted into the rat striatum and one week
      later, 6-hydroxydopamine (6-OHDA) was administered to induce neurotoxicity. It
      was discovered that intrastriatal transplantation of CDNF-BMSCs significantly
      reduced 6-OHDA-induced neurotoxicity in DA neurons with regard to behavioral
      recovery and tyrosine hydroxylase levels in the substantia nigra and striatum.
      These data therefore indicated that transplantation of engineered CDNF-BMSCs into
      the striatum may present a beneficial strategy for the treatment of PD. 

PMID- 25373846
TI  - Investigation of (11)C-PiB equivocal PET findings.
AB  - OBJECTIVE: We have encountered occasional equivocal findings when assessing
      cerebral cortical amyloid retention with (11)C-Pittsburgh compound B (PiB) PET.
      We investigated the diagnostic significance of equivocal PiB PET findings.
      METHODS: This retrospective study included 101 consecutive patients complaining
      of cognitive disorders (30 Alzheimer's disease, 25 mild cognitive impairment, 8
      Lewy body disease, 7 frontotemporal lobar degeneration, 31 others) who underwent
      both (11)C-PiB PET and (18)F-fluorodeoxy-D-glucose (FDG) PET. We visually
      classified PiB-positive, PiB-equivocal or PiB-negative ratings according to
      cortical uptake. For quantitative assessments of PiB PET, standard uptake values
      referred to cerebellar cortex (SUVR) were calculated in regional template volume
      of interests (frontal, temporoparietal, precuneus/posterior cingulate cortex,
      cerebral white matter and cerebellar cortex). The results of visual assessment
      were compared with the regional and mean cortical SUVRs and cortical-to-white
      matter ratio of PiB uptake, as well as clinical and FDG PET findings. RESULTS:
      Among the 101 scans, 41 were PiB negative, 11 were PiB equivocal, and 49 were
      rated PiB positive in the visual assessments. The mean cortical SUVR and cortical
      to-white matter ratio were 0.97 +/- 0.07 and 0.57 +/- 0.21 in PiB-negative, 1.51
      +/- 0.17 and 0.75 +/- 0.06 in PiB equivocal and 2.10 +/- 0.33 and 0.97 +/- 0.11
      in PiB-positive group, respectively. Nine of 11 subjects with PiB-equivocal
      findings had cognitive impairments and FDG distribution compatible with
      Alzheimer's disease or dementia with Lewy bodies. CONCLUSIONS: We considered
      equivocal visual findings on PiB PET equivalent to PiB-positive with slight
      cortical uptake. In addition, slight cortical amyloid deposits were considered to
      cause cerebral metabolic abnormality and cognitive impairment. Although mean
      cortical SUVR was more sensitive than visual assessment because of low cortical
      to-white matter contrast due to non-specific accumulation in white matter, it is
      important not to overlook small amounts of cortical uptake of PiB in visual
      inspection for exact diagnosis.

PMID- 25373847
TI  - Isothiocyanate synthetic analogs: biological activities, structure-activity
      relationships and synthetic strategies.
AB  - Sulforaphane is a natural product that is constantly under biological
      investigation for its unique biological properties. This naturally occurring
      isothiocyanate (ITC) and its analogs are the main components of cruciferous
      vegetables, such as cauliflower, watercress, broccoli, cabbage, Brussels sprouts,
      widely used as chemopreventive agents. Due to their interesting biological
      profiles, natural ITCs have been exploited as starting point to develop new
      synthetic analogs. The present mini-review briefly highlights the most important
      biological actions of selected new synthetic ITCs focusing on their structure
      activity relationships and related synthetic strategies. 

PMID- 25373848
TI  - Synthesis and biological activity of substituted-4,5,6,7-tetrahydrothieno
      pyridines: a review.
AB  - 4,5,6,7-Tetrahydrothieno pyridine is an important class of heterocyclic nucleus.
      Various 4,5,6,7-tetrahydrothieno pyridine derivatives have been synthesized and
      evaluated for various biological activities in different models with desired
      findings. Some analogs have shown potent biological activities and may be
      considered as lead molecule for the development of future drugs. Number of drug
      molecules are available in the market and many molecules are in clinical
      development containing 4,5,6,7-tetrahydrothieno pyridine nucleus as an important
      core. This review is an attempt to organize the chemical and biological aspects
      of 4,5,6,7-tetrahydrothieno pyridine analogs reported in last 20 year to till
      date. Review mainly focuses on the important role of the core in synthesis of
      drug or drug intermediates giving emphasis on synthetic schemes and biological
      activities of the different 4,5,6,7-tetrahydrothieno pyridine analogs. 

PMID- 25373849
TI  - Chemical and medicinal versatility of dithiocarbamates: an overview.
AB  - Dithiocarbamates are considered as the simplest occurring organosulfur compounds
      exhibiting diverse chemical and medicinal versatility. Dithiocarbamates have been
      used as pesticide in the 20(th) century but thereafter they have attracted the
      interest of medicinal chemists due to their metal binding capacity. Recently a
      variety of chemical and medicinal properties of dithiocarbamates have been
      explored other than metal binding capacity. This review collectively describes
      the most significant chemical and medicinal properties of dithiocarbamate
      derivatives reported over the last decade. 

PMID- 25373850
TI  - Role of metalloproteinases in tendon pathophysiology.
AB  - Tendons play a crucial role in musculoskeletal functioning because they
      physically connect bones and muscles making the movement of articular joints
      possible. The molecular composition of tendons mostly include collagen I fibrils,
      which aggregate together to form fibers to form a fascicle. A complex network
      composed of resident cells (i.e., tenocytes) and extracellular matrix
      macromolecules (glycosaminoglycans, proteoglycans, glycoproteins and other non
      collagenous proteins) interact and define the structure of tendons and their
      properties. Development, renewal and remodeling of tendons composition occur at
      all ages of living organisms so the homeostasis of proteolytic systems is a
      critical issue. A major role is played by Metalloproteinases, a family of Zn(2+)
      dependent endopeptidases involved in the catabolism of several components of the
      extracellular matrix, such as collagens, proteoglycans, fibronectin and many
      others. Among these, two main classes are mostly involved in tendon
      pathophysiology, namely the Matrix Metalloproteinases (MMPs) and a Disintegrin
      like and Metalloproteinase domain with Thrombospondin motifs (ADAMTSs). This
      study analyses the various aspects of the roles played by Metalloproteinases in
      the physiological and pathological processes of tendons. 

PMID- 25373851
TI  - Pentraxin-3 concentrations in stable coronary artery disease depend on the
      clinical presentation.
AB  - INTRODUCTION: Pentraxin-3 (PTX3) is an acute-phase reactant that shares
      structural and functional homology with C-reactive protein (CRP). However, unlike
      CRP, which is synthesized mainly in the liver, PTX3 is produced at the site of
      inflammation. It has been suggested that PTX3 plays the same role in the
      periphery that CRP does in circulation. PTX3 may represent a rapid marker of
      local inflammation. METHODS: Fifty-one patients with stable coronary artery
      disease (CAD) were enrolled. Blood samples were collected on admission. Plasma
      concentration of PTX3 and high-sensitivity CRP (hsCRP) were determined. RESULTS:
      Median PTX3 concentration was 0.92 MUmol/L (0.58-1.40). Median hsCRP
      concentration was 0.90 mg/L (0.75-1.10). There was a positive correlation between
      PTX3 and total cholesterol (R=0.34; P=0.01), PTX3 and LDL cholesterol (R=0.35;
      P=0.01), and PTX3 and hsCRP (R=0.46; P = 0.0005). We found no correlation between
      hsCRP and all laboratory parameters. We found higher PTX3 concentrations in
      patients with Canadian Cardiovascular Society (CCS) functional class 3 (compared
      to CCS functional class 2) and in patients taking nitrates. Lower PTX3
      concentrations were reported in patients taking calcium channel blockers
      (amlodipine). hsCRP concentrations remained similar among these subgroups of
      patients. CONCLUSIONS: PTX3 is a marker of clinically more advanced CAD (CCS2 vs
      CCS3; nitrates vs no nitrates). PTX3 is also associated with other cardiovascular
      risk factors (total cholesterol, LDL cholesterol, and hsCRP). PTX3 may be a
      potential early marker of cardiovascular risk before the increase of systemic
      markers like hsCRP.

PMID- 25373852
TI  - Increased circulating RANTES in type 2 diabetes.
AB  - AIM: The pro-atherogenic role of RANTES, a chemokine expressing pleiotropic
      activities, in the course of type 2 diabetes-related atherosclerosis has been
      well documented. However, it is not known which of the diabetes-related factors
      primarily influence serum RANTES levels in patients with type 2 diabetes. Our aim
      was to investigate relationships between several factors known to be related to
      an increased risk of atherosclerosis and serum RANTES levels in type 2 diabetic
      patients. METHODS: A total of 168 subjects were examined, which included 138
      patients with type 2 diabetes and 30 non-diabetic controls. Measurements of
      venous, fasting, plasma glucose, HbA1c, lipid profile, 1,5-anhydro-D-glucitol
      (1,5-AG) plasma levels, homocysteine and the fasting, serum C-peptide levels were
      performed. Serum concentrations of RANTES were assayed using BD(TM) Cytometric
      Bead Array tests. Peripheral insulin resistance was expressed according to a new
      index defined by Ohkura et al. RESULTS: RANTES levels in type 2 diabetic patients
      correlated with 1,5-AG, fasting glycaemia, HbA1c and the Ohkura index.
      Multivariate regression analysis was performed taking into consideration several
      factors related to the inflammatory process and atherosclerosis, namely the
      patient's age, diabetes duration, waist circumference, 1,5-AG, HbA1c, lipid
      profile parameters, serum homocysteine levels and Ohkura index, as independent
      variables potentially influencing serum RANTES levels in type 2 diabetic
      patients. It is shown that RANTES concentrations in the serum is primarily
      dependent upon 1,5-AG plasma levels. CONCLUSION: Our results suggest that
      increased serum levels of RANTES in type 2 diabetic patients are closely related
      to postprandial (acute) hyperglycaemia.

PMID- 25373853
TI  - Effect of acute sleep deprivation and recovery on Insulin-like Growth Factor-I
      responses and inflammatory gene expression in healthy men.
AB  - Acute sleep deprivation in humans has been found to increase inflammatory markers
      and signaling pathways in the periphery through a possible Toll-like receptor 4
      (TLR-4). In addition, short duration sleep has been associated with low
      circulating total Insulin-like Growth Factor-I (IGF-I) concentrations. We aimed
      to determine whether a total sleep deprivation (TSD) protocol with recovery
      altered whole-blood gene expression of the proinflammatory cytokines TNF-alpha
      and IL-6, as well as TLR-4 expression, and to examine the relationship with
      circulating concentrations of the IGF-I system. Twelve healthy men participated
      in a five-day TSD (two control nights followed by one night of sleep deprivation
      and one night of recovery). Blood was sampled at 0800, before and after sleep
      deprivation (D2 and D4), and after recovery (D5). It is shown that 25 h of sleep
      deprivation (D4) induced significant increases in mRNA levels of TNF-alpha and
      its soluble receptor R1 (P<0.01 respectively), as well as TLR-4 (P<0.05), while
      IL-6 mRNA levels remained unchanged. Circulating concentrations of free IGF-I
      were decreased at D4 (P<0.001). One night of recovery was sufficient to restore
      basal expression levels for TNF-alpha, sTNF-R1, TLR-4 and circulating IGF-I.
      Changes in TLR-4 mRNA levels during the protocol correlated positively with those
      of TNF-alpha and sTNF-R1 (r=0.393 and r=0.490 respectively), and negatively with
      circulating free IGF-I (r=-0.494). In conclusion, 25 h of sleep deprivation in
      healthy subjects is sufficient to induce transient and reversible genomic
      expression of the pro-inflammatory cytokine TNF-alpha and its R1 receptor, and
      its mediator TLR-4, with a possible link to IGF-I axis inhibition.

PMID- 25373854
TI  - Timing and characteristics of radiation pneumonitis after stereotactic body
      radiotherapy for peripherally located stage I lung cancer.
AB  - BACKGROUND: This study was conducted to determine the timing and characteristics
      of radiation pneumonitis (RP) associated with stereotactic body radiotherapy
      (SBRT) for stage I lung cancer. METHODS: Two hundred thirty-one patients treated
      with SBRT using 52 Gy in 4 fractions were identified. Control rate, RP incidence
      rate, and predictive factors and timing of RP were evaluated retrospectively.
      RESULTS: The 3-year overall survival and local control rates were 80.7 and 92.0
      %, respectively. The grade >=2 RP rate was 13.0 %; no grade 4-5 RP occurred. The
      most statistically significant predictive factor of grade >=2 RP was V10. The
      median intervals to first graphical appearance were 4.2 and 2.5 months for grade
      1 and grade 2-3 RP, respectively. Median intervals to maximum radiological
      density change were 6.0 and 4.6 months for grade 1 and grade 2-3 RP,
      respectively. A significantly different interval to first graphical appearance
      between grade 1 and grade 2-3 RP was observed; no significantly different
      interval to maximum radiological density change was noted. CONCLUSIONS: The first
      graphical appearance of grade >=2 RP was earlier than that of grade 1 RP,
      although the timing of maximum radiological density change was not significantly
      different.

PMID- 25373855
TI  - Hand transplants and the mandate for tolerance.
AB  - PURPOSE OF REVIEW: The field of vascularized composite allograft (VCA) to achieve
      its full potential will require induction of tolerance. This review will
      introduce a new method of potential inducing tolerance in hand transplantation.
      RECENT FINDINGS: Hand transplantation is never a life-extending transplant. This
      fact resulted in considerable debate both for and against the use of
      immunosuppression for nonlife-extending transplants. There is considerable debate
      about the ethics of hand transplantation. There is now consensus that nonlife
      extending transplants are acceptable in properly selected patients. However,
      ideally, hand transplants should not receive life-long immunosuppression.
      Therefore, attempts to achieve drug-free tolerance through nonlife-endangering
      therapies are warranted. To this end, we propose implementation of tolerizing
      therapy long after periinflammation has subsided and drug minimization has proven
      successful. Evidence that short-term treatment with low doses of IL-2 or a long
      lived IL-2 immunoglobulin (Ig) can tilt the balance of immunity from tissue
      destructive to tolerance come from preclinical demonstrations in mouse and
      nonhuman primate models of autoimmunity and/or transplantation and even more
      recent clinical trials. SUMMARY: We believe that with the proper use of low-dose
      IL-2 given at an opportune time in the inflammatory process of transplant that
      reduce immunosuppression and even tolerance can be induced in hand
      transplantation. We propose that tolerance can be inducted after a long period of
      conventional treatment to avoid 'tolerance-hindering' adverse inflammation that
      occurs in the posttransplant period. With abatement of posttransplant
      inflammation and with time, we will institute low-dose IL-2-based therapy to
      support the proliferation, viability and functional phenotype of regulatory T
      cells.

PMID- 25373857
TI  - Gastrointestinal manifestations in diploid/triploid mixoploidy.
AB  - A girl infant was delivered by cesarean section at 32 weeks of gestation because
      of growth arrest and poor movement patterns. The infant had feeding problems,
      which were based on gastroesophageal reflux, laryngomalacia, and decreased gut
      motility. Hypotonia was notable from the outset, and the patient eventually
      displayed significant delays in both motor and cognitive milestones. Meanwhile,
      lymphocytes had yielded a normal karyotype (46,XX), but at 2 years of age the
      patient underwent a skin biopsy and mosaicism because a 68,XX cell line was
      discovered in fibroblasts. At the age 6.4 years, the patient is short of stature
      below the 3rd percentile but has a weight at the 42nd percentile and head
      circumference above the 97th percentile. Other phenotypic features include low
      set ears, piebald irides and scalp hair, eyelid ptosis, strabismus, broad nasal
      bridge, anteverted nares, upswept eyebrows, hypoplastic teeth, pectus excavatum,
      hypoplastic labia, scoliosis, 3-4 finger syndactyly, and 2-3 toe syndactyly. We
      present this case with a review of the literature for mixoploidy (the rare event
      of mosaicism for diploid and triploid cell lines). We add to the existing data on
      the clinical features of diploid/triploid mixoploidy. The complexities of the
      gastrointestinal problems make this case unusual. 

PMID- 25373858
TI  - On the origin of pediatric nonalcoholic Fatty liver disease.

PMID- 25373859
TI  - Taking full measure of the pediatric ulcerative colitis activity index.

PMID- 25373860
TI  - Clinical features of interleukin 10 receptor gene mutations in children with very
      early-onset inflammatory bowel disease.
AB  - OBJECTIVES: In the present study, we studied a cohort of patients with very early
      onset inflammatory bowel disease (IBD) to determine the frequency of mutations in
      the interleukin 10 (IL10) receptor genes as a cause of early-onset IBD. METHODS:
      Sanger sequencing was performed to determine the presence of IL10 and/or IL10
      receptor mutations in 17 patients with a diagnosis of very early onset IBD
      (disease onset <2 years of age in 15 patients, between 3 and 4 years in the other
      2). Mutation screening was performed including all of the coding regions of the
      IL10, IL10RA, and IL10RB genes. We then compared the follow-up findings of the
      patients with IL10 receptor mutations in terms of demographic, clinical,
      laboratory, and treatment response properties with those of patients diagnosed as
      having very early onset IBD with no mutation. RESULTS: We identified 3 patients
      bearing mutations in the IL10 or IL10 receptor genes, including 1 mutation in
      IL10RB that has been described recently (c.G477A, p.Trp159*) and 2 novel
      mutations affecting the IL10RA gene (c.T192G, p.Tyr64 and c.T133G, p.Trp45Gly).
      Collectively, these mutations thus provided genetic etiology for 17.6% of the
      cohort under investigation. The presence of a family history of IBD and the
      clinical course of Crohn disease differed between patients with mutations in the
      IL-10 pathway and those without such mutations. Although perianal fistulas were
      found in all of the patients with IL10 receptor mutations, they were found in
      only 14.3% of those without such mutations. The lower values of weight-for-age
      and height-for-age z scores, necessity for more intensive therapy, achievement of
      longer periods until remission, and frequent relapses in the patients bearing
      mutations in the IL10 receptor genes all underlined the severity of the disease
      and its relatively poor response to treatment. CONCLUSIONS: In spite of the small
      number of patients with mutations affecting the IL-10 signaling pathway in our
      study, in all of the patients with IL10 receptor mutations, the disease onset
      occurs at an early age, the prognosis is poor, and the response to treatment is
      insufficient.

PMID- 25373861
TI  - Too early to determine whether fecal microbiota transplant has therapeutic
      promise for Ulcerative Colitis?

PMID- 25373862
TI  - Can lipidomics conceal the key for understanding celiac disease?

PMID- 25373863
TI  - Surgery and postoperative recurrence in children with Crohn disease.
AB  - OBJECTIVES: The aim of this study was to describe surgery rates, complications,
      and risk of disease recurrence after surgery in paediatric Crohn disease (CD).
      METHODS: Children <18 years with a diagnosis of CD and a least 1 intestinal
      resection from the period January 1, 1978 to December 31, 2007 were identified
      using the Danish National Patient Registry. Patient charts were used to extract
      data. RESULTS: A total of 115 of 422 children with CD, who had surgery in 2
      referral centres, were further studied. Disease extension according to the
      Montreal classification at the time of operation was available in 106/115
      patients: B1, 39/106 (37%); B2, 59/106 (56%); and B3, 8/106 (7%). Before/after
      surgery 89%/36% of the patients received corticosteroids, 26%/61% azathioprine,
      and 15%/34% infliximab. Ileocoecal resection was performed in 54 (47%); 17 (15%)
      underwent ileal resection, 21 (18%) colectomy, 13 (11%) hemicolectomy, and 10
      (9%) a combined colonic and ileal resection. Median time from diagnosis to
      surgery was 23 months (range 0-147). The median follow-up time after surgery was
      121 months (16-226), and median time to disease recurrence was 12 months (3-160).
      The cumulative clinical recurrence rates at 1, 5, and 10 years were 50%, 73%, and
      77%, respectively. More than 1 bowel resection was needed in 39%. Postoperative
      azathioprine treatment did not affect rate of recurrence after surgery.
      CONCLUSIONS: In this large cohort of children with CD studied for >10 years
      postoperatively, we found a high postoperative recurrence rate of disease and a
      frequent need for >1 intestinal resection.

PMID- 25373864
TI  - Faecal calprotectin in suspected paediatric inflammatory bowel disease.
AB  - OBJECTIVES: The diagnostic accuracy of faecal calprotectin (FC) concentration for
      paediatric inflammatory bowel disease (IBD) is well described at the population
      level, but not at the individual level. We reassessed the diagnostic accuracy of
      FC in children with suspected IBD and developed an individual risk prediction
      rule using individual patient data. METHODS: MEDLINE, EMBASE, DARE, and MEDION
      databases were searched to identify cohort studies evaluating the diagnostic
      performance of FC in paediatric patients suspected of having IBD. A standard
      study-level meta-analysis was performed. In an individual patient data meta
      analysis, we reanalysed the diagnostic accuracy on a merged patient dataset.
      Using logistic regression analysis we investigated whether and how the FC value
      and patient characteristics influence the diagnostic precision. A prediction rule
      was derived for use in clinical practice and implemented in a spreadsheet
      calculator. RESULTS: According to the study-level meta-analysis (9 studies,
      describing 853 patients), FC has a high overall sensitivity of 0.97 (95%
      confidence interval [CI] 0.92-0.99) and a specificity of 0.70 (0.59-0.79) for
      diagnosing IBD. In the patient-level pooled analysis of 742 patients from 8
      diagnostic accuracy studies, we calculated that at an FC cutoff level of 50 MUg/g
      there would be 17% (95% CI 15-20) false-positive and 2% (1-3) false-negative
      results. The final logistic regression model was based on individual data of 545
      patients and included both FC level and age. The area under the receiver
      operating characteristic curve of this derived prediction model was 0.92 (95% CI
      0.89-0.94). CONCLUSIONS: In high-prevalence circumstances, FC can be used as a
      noninvasive biomarker of paediatric IBD with only a small risk of missing cases.
      To quantify the individual patients' risk, we developed a simple prediction model
      based on FC concentration and age. Although the derived prediction rule cannot
      substitute the clinical diagnostic process, it can help in selecting patients for
      endoscopic evaluation.

PMID- 25373865
TI  - Gastroesophageal reflux in young children and adolescents: Is there a relation
      between symptom severity and esophageal histological grade?
AB  - BACKGROUND: The pediatric literature about the correlation between symptoms and
      histological lesions in patients investigated for gastroesophageal reflux disease
      is scarce and inconclusive. The primary aim of the present study was to assess
      the relation between the complained symptom severity and the esophageal
      histological grade, through the use of validated and reliable scores. METHODS:
      All children ages between 2 and 17 years referred to perform upper
      gastrointestinal endoscopy because of gastroesophageal reflux disease symptoms
      were asked to complete the Pediatric Gastroesophageal Symptom and Quality of Life
      validated questionnaire, investigating the main symptoms complained and their
      impact on daily life and school activities. Esophageal mucosal samples taken
      during the procedure were analyzed and scored according to the Yerian-Fiocca
      classification. RESULTS: A total of 164 children were included in the study. No
      significant association was found between symptomatic score and histological
      score (r(s): 0.05, P: 0.49). Even when focusing only on adolescents with
      heartburn or chest pain, no correlation between symptom severity and esophageal
      lesions was found (r(s): -0.18, P: 0.264). Intercellular space diameter values
      did not mirror symptom severity. CONCLUSIONS: The main finding of this study on
      children with reflux symptoms is the lack of correlation between symptom severity
      and esophageal histological grade. The magnitude of intercellular spaces was
      found not to be related with the clinical score as well.

PMID- 25373866
TI  - Upgrading a microplate reader for photobiology and all-optical experiments.
AB  - Automation can vastly reduce the cost of experimental labor and thus facilitate
      high experimental throughput, but little off-the-shelf hardware for the
      automation of illumination experiments is commercially available. Here, we use
      inexpensive open-source electronics to add programmable illumination capabilities
      to a multimode microplate reader. We deploy this setup to characterize light
      triggered phenomena in three different sensory photoreceptors. First, we study
      the photoactivation of Arabidopsis thaliana phytochrome B by light of different
      wavelengths. Second, we investigate the dark-state recovery kinetics of the
      Synechocystis sp. blue-light sensor Slr1694 at multiple temperatures and
      imidazole concentrations; while the kinetics of the W91F mutant of Slr1694 are
      strongly accelerated by imidazole, the wild-type protein is hardly affected.
      Third, we determine the light response of the Beggiatoa sp. photoactivatable
      adenylate cyclase bPAC in Chinese hamster ovary cells. bPAC is activated by blue
      light in dose-dependent manner with a half-maximal intensity of 0.58 mW cm(-2);
      intracellular cAMP spikes generated upon bPAC activation decay with a half time
      of about 5 minutes after light switch-off. Taken together, we present a setup
      which is easily assembled and which thus offers a facile approach to conducting
      illumination experiments at high throughput, reproducibility and fidelity. 

PMID- 25373867
TI  - Modulation of cellular stress response via the erythropoietin/CD131
      heteroreceptor complex in mouse mesenchymal-derived cells.
AB  - Tissue-protective properties of erythropoietin (EPO) have let to the discovery of
      an alternative EPO signaling via an EPO-R/CD131 receptor complex which can now be
      specifically targeted through pharmaceutically designed short sequence peptides
      such as ARA290. However, little is still known about specific functions of
      alternative EPO signaling in defined cell populations. In this study, we
      investigated effects of signaling through EPO-R/CD131 complex on cellular stress
      responses and pro-inflammatory activation in different mesenchymal-derived
      phenotypes. We show that anti-apoptotic, anti-inflammatory effects of ARA290 and
      EPO coincide with the externalization of CD131 receptor component as an immediate
      response to cellular stress. In addition, alternative EPO signaling strongly
      modulated transcriptional, translational, or metabolic responses after stressor
      removal. Specifically, we saw that ARA290 was able to overcome a TNFalpha
      mediated inhibition of transcription factor activation related to cell stress
      responses, most notably of serum response factor (SRF), heat shock transcription
      factor protein 1 (HSF1), and activator protein 1 (AP1). We conclude that
      alternative EPO signaling acts as a modulator of pro-inflammatory signaling
      pathways and likely plays a role in restoring tissue homeostasis. Key message:
      Erythropoietin (EPO) triggers an alternative pathway via heteroreceptor
      EPO/CD131. ARA290 peptide specifically binds EPO/CD131 but not the canonical
      EPO/EPO receptor. Oxidative stress and inflammation promote cell surface
      expression of CD131. ARA290 prevents tumor necrosis factor-mediated inhibition of
      stress-related genes. Alternative EPO signaling modulates inflammation and
      promotes tissue homeostasis.

PMID- 25373868
TI  - Involvement of nitric oxide in improving stress-induced behavioural alteration by
      glatiramer acetate treatment in female BALB/c mice.
AB  - RATIONALE: Oxidative stress and neurotrophins are among the most important
      factors involved in several pathophysiological brain processes. In addition, long
      term exposure to stressful situations has deleterious effects on behaviour. We
      have previously shown that stressed female BALB/c mice show poor learning
      performance and that this behaviour is reversed by glatiramer acetate (GA)
      treatment. OBJECTIVES: We investigated the involvement of the hippocampal
      oxidative status and neurotrophin levels in cognitive deficit and the improvement
      of this deficit by GA treatment in chronic stressed BALB/c mice. METHODS: Female
      BALB/c mice were exposed to a chronic mild stress (CMS) model for 9 weeks. During
      the last 3 weeks of the stress exposure, one group of mice was subcutaneously
      injected four times with 100 MUg GA/mouse. Following this period, behavioural
      studies were performed. The mice were then sacrificed, and biochemical studies
      were performed on the hippocampus. RESULTS: The stressed mice exhibited a
      significant decline in their performance in the open-field and in object-in-place
      tasks. This decline was accompanied by an increase in reactive oxygen species
      (ROS) and a decrease in nitric oxide (NO) production by neuronal nitric oxide
      synthase (nNOS). Neither antioxidant defences nor neurotrophin protein levels
      were involved in this process. Interestingly, the administration of GA re
      established the normal levels of ROS, restored nNOS activity and improved
      learning performance. CONCLUSIONS: The GA treatment improved learning and memory
      in female BALB/c mice under chronic stress through a mechanism that involves the
      regulation of NO production, which in turn modulates the ROS levels.

PMID- 25373869
TI  - Effects of anticholinergic challenge on psychopathology and cognition in drug
      free patients with schizophrenia and healthy volunteers.
AB  - RATIONALE: Many aspects of the neurobiology of schizophrenia, especially the
      physiological basis of the negative symptoms and associated cognitive deficits,
      remain inadequately understood. Tandon and Greden (1989) postulated a central
      role of dopaminergic/cholinergic imbalance in schizophrenia. OBJECTIVE/METHODS:
      In light of this hypothesis, we elected to investigate the effects of
      anticholinergic challenge on psychopathology, cognition and attention in 12
      unmedicated patients with schizophrenia and 12 healthy controls. The first
      examination occurred before any pharmacological intervention; the second
      examination was carried out immediately following an intravenous infusion of 5 mg
      biperiden, a centrally acting antimuscarinergic agent. RESULTS: The biperiden
      challenge provoked a considerable increase in PANSS scores in both groups which
      was significantly more pronounced in patients (repeated measures analysis of
      variance (ANOVA) (rmANOVA): F(df) = 6.4(1,22); p = 0.019). The increase in the
      PANSS scores showed a significant negative correlation with age in patients.
      Biperiden caused considerable cognitive impairments in both groups. A significant
      group difference (rmANOVA) could be observed for TMT-B (F(df) = 11.29(1,22); p =
      0.003). CONCLUSIONS: The anticholinergic intervention caused more pronounced
      psychopathological and cognitive deteriorating effects in patients suffering from
      schizophrenia than in healthy volunteers. This could be related to the disrupted
      cholinergic transmission in schizophrenia. Our findings speak on behalf of the
      need of a more restrictive use of anticholinergics in psychiatric patients. The
      age-related attenuation of PANSS score increases in patients could be related to
      the age-dependent changes in dopamine dynamics and also to the age-associated
      decline of the availability of muscarinic receptors. Our results emphasise the
      need for further investigation of cholinergic disturbances in schizophrenia.

PMID- 25373870
TI  - Social defeat stress-induced sensitization and escalated cocaine self
      administration: the role of ERK signaling in the rat ventral tegmental area.
AB  - RATIONALE: Intermittent social defeat stress can induce neuroadaptations that
      promote compulsive drug taking. Within the mesocorticolimbic circuit, repeated
      cocaine administration activates extracellular signal-regulated kinase (ERK).
      OBJECTIVE: The present experiments examine whether changes in ERK phosphorylation
      are necessary for the behavioral and neural adaptations that occur as a
      consequence of intermittent defeat stress. MATERIALS AND METHODS: Rats were
      exposed to four brief intermittent defeats over the course of 10 days. Ten days
      after the last defeat, rats were challenged with cocaine (10 mg/kg, i.p.) or
      saline, and ERK activity was examined in mesocorticolimbic regions. To determine
      the role of ERK in defeat stress-induced behavioral sensitization, we bilaterally
      microinjected the MAPK/ERK kinase inhibitor U0126 (1 MUg/side) or vehicle (20 %
      DMSO) into the ventral tegmental area (VTA) prior to each of four defeats. Ten
      days following the last defeat, locomotor activity was assessed for the
      expression of behavioral cross-sensitization to cocaine (10 mg/kg, i.p.).
      Thereafter, rats self-administered cocaine under fixed and progressive ratio
      schedules of reinforcement, including a 24-h continuous access "binge" (0.3
      mg/kg/infusion). RESULTS: We found that repeated defeat stress increased ERK
      phosphorylation in the VTA. Inhibition of VTA ERK prior to each social defeat
      attenuated the development of stress-induced sensitization and prevented stress
      induced enhancement of cocaine self-administration during a continuous access
      binge. CONCLUSIONS: These results suggest that enhanced activation of ERK in the
      VTA due to brief defeats is critical in the induction of sensitization and
      escalated cocaine taking.

PMID- 25373871
TI  - Multimedia model for polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs in
      Lake Michigan.
AB  - Polycyclic aromatic hydrocarbon (PAH) contamination in the U.S. Great Lakes has
      long been of concern, but information regarding the current sources,
      distribution, and fate of PAH contamination is lacking, and very little
      information exists for the potentially more toxic nitro-derivatives of PAHs
      (NPAHs). This study uses fugacity, food web, and Monte Carlo models to examine 16
      PAHs and five NPAHs in Lake Michigan, and to derive PAH and NPAH emission
      estimates. Good agreement was found between predicted and measured PAH
      concentrations in air, but concentrations in water and sediment were generally
      under-predicted, possibly due to incorrect parameter estimates for degradation
      rates, discharges to water, or inputs from tributaries. The food web model
      matched measurements of heavier PAHs (>=5 rings) in lake trout, but lighter PAHs
      (<=4 rings) were overpredicted, possibly due to overestimates of metabolic half
      lives or gut/gill absorption efficiencies. Derived PAH emission rates peaked in
      the 1950s, and rates now approach those in the mid-19th century. The derived
      emission rates far exceed those in the source inventories, suggesting the need to
      reconcile differences and reduce uncertainties. Although additional measurements
      and physiochemical data are needed to reduce uncertainties and for validation
      purposes, the models illustrate the behavior of PAHs and NPAHs in Lake Michigan,
      and they provide useful and potentially diagnostic estimates of emission rates. 

PMID- 25373872
TI  - Mono- versus polyaxial locking plates in distal femur fractures - a biomechanical
      comparison of the Non-Contact-Bridging- (NCB) and the PERILOC-plate.
AB  - BACKGROUND: The aim of this cadaveric study was to compare a polyaxial (NCB(r),
      Zimmer) to a fixed-angle monoaxial locking plate (PERILOC(r), Smith & Nephew) in
      comminuted fractures of the distal femur regarding stability of the construct. Up
      to date there is no published biomechanical data concerning polyaxial plating in
      cadaveric distal femurs. METHODS: Fourteen formalin fixed femora were scanned by
      dual-energy x-ray absorptiometry. As fracture model an unstable supracondylar
      comminuted fracture was simulated. Fractures were pairwise randomly fixed either
      with a mono- (group A) or a polyaxial (group B) distal femur plate. The samples
      were tested in a servohydraulic mechanical testing system starting with an axial
      loading of 200 N following an increase of 200 N in every step with 500 cycles in
      every sequence up to a maximum of 2 000 N. The end points were implant failure or
      relevant loss of reduction. Data records included for each specimen time, number
      of cycles, axial load and axial displacement. Statistical analysis was performed
      using the exact Wilcoxon signed rank test. RESULTS: The mean donor age at the
      time of death was 75 years. The bone mass density (BMD) of the femurs in both
      groups was comparable and showed no statistically significant differences. Five
      bones failed before reaching the maximum applied force of 2000 N. Distribution
      curves of all samples in both groups, showing the plastic deformation in relation
      to the axial force, showed no statistically significant differences. CONCLUSIONS:
      Operative stabilization of distal femur fractures can be successfully and equally
      well achieved using either a monoaxial or a polyaxial locking plate. Polyaxial
      screw fixation may have advantages if intramedullary implants are present.

PMID- 25373873
TI  - Seasonal variation of child under nutrition in Malawi: is seasonal food
      availability an important factor? Findings from a national level cross-sectional
      study.
AB  - BACKGROUND: Child under nutrition is an underlying factor in millions of under
      five child deaths and poor cognitive development worldwide. Whilst many studies
      have examined the levels and factors associated with child under nutrition in
      different settings, very little has been written on the variation of child under
      nutrition across seasons. This study explored seasonal food availability and
      child morbidity as influences of child nutritional status in Malawi. METHODS: The
      study used the 2004 Malawi Integrated Household Survey data. Graphical analysis
      of the variation of child under nutrition, child morbidity and food availability
      across the 12 months of the year was undertaken to display seasonal patterns over
      the year. Multivariate analysis was used to explore the importance of season
      after controlling for well-established factors that are known to influence a
      child's nutritional status. RESULTS: A surprising finding is that children were
      less likely to be stunted and less likely to be underweight in the lean cropping
      season (September to February) compared to the post-harvest season (March to
      August). The odds ratio for stunting were 0.80 (0.72, 0.90) and the odds ratio
      for underweight were 0.77 (0.66, 0.90). The season when child under nutrition
      levels were high coincided with the period of high child morbidity in line with
      previous studies. Children that were ill in the two weeks prior to survey were
      more likely to be underweight compared to children that were not ill 1.18 (1.01,
      1.38). CONCLUSION: In Malawi child nutritional status varies across seasons and
      follows a seasonal pattern of childhood illness but not that of household food
      availability.

PMID- 25373875
TI  - Effect of telemedicine follow-up care of leg and foot ulcers: a systematic
      review.
AB  - BACKGROUND: Leg ulcers and diabetes-related foot ulcers are frequent and costly
      complications of their underlying diseases and thus represent a critical issue
      for public health. Since the population is aging, the prevalence of these
      conditions will probably increase considerably and require more resources.
      Treatment of leg and foot ulcers often demands frequent contact with the health
      care system, may pose great burden on the patient, and involves follow-up in both
      primary and specialist care. Telemedicine provides potential for more effective
      care management of leg and foot ulcers. The objective of this systematic review
      of the literature was to assess the effect of telemedicine follow-up care on
      clinical, behavioral or organizational outcomes among patients with leg and foot
      ulcers. METHODS: We searched Ovid MEDLINE (1980-), Ovid EMBASE (1980-), Clinical
      Trials in the Cochrane Library (via Wiley), Ebsco CINAHL with Fulltext (1981-)
      and SveMed + (1977-) up to May 2014 for relevant articles. We considered
      randomized controlled trials, non-randomized trials, controlled before-after
      studies and prospective cohort studies for inclusion and selected studies
      according to predefined criteria. Three reviewers independently assessed the
      included studies using the Cochrane Collaboration risk-of-bias tool. We performed
      a narrative synthesis of results and assessed the strength of evidence for each
      outcome using GRADE (grading of recommendations, assessment, development and
      evaluation). RESULTS: Only one non-randomized study was included. The study (n =
      140) measured the effect of real-time interactive video consultation compared
      with face-to-face follow-up on healing time, adjusted healing ratio and the
      number of ulcers at 12 weeks among patients with neuropathic forefoot
      ulcerations. There were no statistically significant differences in results of
      the different outcomes between patients receiving telemedicine and traditional
      follow-up. We assessed the study to have a high risk of bias. CONCLUSIONS: There
      is insufficient evidence available to unambiguously determine whether
      telemedicine consultation of leg and foot ulcers is as effective as traditional
      follow-up.

PMID- 25373877
TI  - International Summit 2014: Organisation of clinical ultrasound in the world.
AB  - Ultrasound (US) is a widely used imaging modality throughout the world, yet
      differences in usage remain among countries or regions, according to the results
      of the International Summit, organised by the ESR during the European Congress of
      Radiology last March in Vienna. The International Summit is held each year by the
      ESR and its partner national and international societies of radiology from
      outside Europe with the primary goal of gathering information about a particular
      topic in radiology from a worldwide perspective. In 2014, some aspects of the
      practice of US imaging within and outside radiology were discussed, following a
      list of items prepared by the ESR Working Group on Ultrasound. Results showed
      that radiological US has similar problems throughout the world. At the same time,
      however, there are profound differences in how US is practised and the results of
      this meeting should be considered with caution. The results of the International
      Summit offer an overview of the major trends and differences in the use of US
      worldwide, but as a whole suggest that this imaging technique still plays a major
      role in radiology and health care.Main messages* US is a widely used modality and
      constitutes a great part of radiological workload.* The use of ultrasound is
      split between radiological and non-radiological services.* Training differs among
      countries and the presence of local subspecialty societies improves training
      quality.* The shortage of local radiologists and lack of interest among young
      radiologists are worrying.* US use should not be limited to radiologists alone,
      especially in sparsely populated areas. 

PMID- 25373876
TI  - Evaluation of the Cepheid Xpert MTB/RIF assay.
AB  - The lack of capacity to provide laboratory confirmation of a diagnosis of
      tuberculosis disease (TB) is contributing to enormous gaps in the ability to
      find, treat and follow TB patients. WHO estimates that globally only about 57% of
      the notified new cases of pulmonary TB in 2012 and about 19% of rifampicin
      resistant TB cases were laboratory confirmed. The Cepheid Xpert((r)) MTB/RIF
      assay has been credited with revolutionizing laboratory testing to aid in the
      diagnosis of TB and rifampicin-resistant TB. This semi-automated test can detect
      both the causative agent of TB and mutations that confer rifampicin resistance
      from clinical specimens within 2 h after starting the test. In this article, we
      review the performance of the test, its pathway to regulatory approval and
      endorsement, guidelines for its use and lessons learned from the implementation
      of the test in low-burden, high-resource countries and in high-burden, low
      resource countries. 

PMID- 25373879
TI  - Pharmacokinetics of metoclopramide in calves with renal dysfunction.
AB  - To clarify the effect of renal dysfunction on pharmacokinetics of the prokinetic
      agent metoclopramide (MCP), we administered intravenously 0.4 mg/kg MCP to
      healthy calves and calves subjected to right kidney vessel ligation (ligation)
      without or with a subsequent left nephrectomy (ligation plus removal). Plasma MCP
      concentration, glomerular filtration rate (GFR) and plasma prolactin level were
      measured by liquid chromatography-tandem mass spectrometry, simplified equation
      using iodixanol and enzyme-linked immunosorbent assay, respectively. Only in
      calves with ligation plus removal, plasma MCP concentrations were increased
      significantly 6, 8 and 12 hr after injection, showing that a negative correlation
      was observed between the plasma MCP concentrations and GFR value. A tendency to
      increase in plasma PRL concentration was noted also in these calves. In
      conclusions, plasma MCP concentrations depend on the GFR mode in calves, and its
      critical GFR value was estimated. 

PMID- 25373878
TI  - Emerging importance of oxidative stress in regulating striated muscle elasticity.
AB  - The contractile function of striated muscle cells is altered by
      oxidative/nitrosative stress, which can be observed under physiological
      conditions but also in diseases like heart failure or muscular dystrophy.
      Oxidative stress causes oxidative modifications of myofilament proteins and can
      impair myocyte contractility. Recent evidence also suggests an important effect
      of oxidative stress on muscle elasticity and passive stiffness via modifications
      of the giant protein titin. In this review we provide a short overview of known
      oxidative modifications in thin and thick filament proteins and then discuss in
      more detail those oxidative stress-related modifications altering titin stiffness
      directly or indirectly. Direct modifications of titin include reversible
      disulfide bonding within the cardiac-specific N2-Bus domain, which increases
      titin stiffness, and reversible S-glutathionylation of cryptic cysteines in
      immunoglobulin-like domains, which only takes place after the domains have
      unfolded and which reduces titin stiffness in cardiac and skeletal muscle.
      Indirect effects of oxidative stress on titin can occur via reversible
      modifications of protein kinase signalling pathways (especially the NO-cGMP-PKG
      axis), which alter the phosphorylation level of certain disordered titin domains
      and thereby modulate titin stiffness. Oxidative stress also activates proteases
      such as matrix-metalloproteinase-2 and (indirectly via increasing the
      intracellular calcium level) calpain-1, both of which cleave titin to
      irreversibly reduce titin-based stiffness. Although some of these mechanisms
      require confirmation in the in vivo setting, there is evidence that oxidative
      stress-related modifications of titin are relevant in the context of biomarker
      design and represent potential targets for therapeutic intervention in some forms
      of muscle and heart disease. 

PMID- 25373880
TI  - Expression of cell adhesion molecules in canine choroid plexus tumors.
AB  - Choroid plexus tumor (CPT) is a primary intracranial neoplasm of the choroid
      plexus epithelium in the central nervous system. In the current World Health
      Organization classification, CPT is classified into two categories; choroid
      plexus papilloma (CPP) and carcinoma (CPC). In the present study, we investigated
      immunohistochemical expressions of N-cadherin, E-cadherin and beta-catenin in 5
      canine CPT cases (1 disseminated CPC, 2 CPCs and 2 CPPs). One CPP case was
      positive for N-cadherin and beta-catenin, but negative for E-cadherin. The
      disseminated CPC case was positive for E-cadherin and beta-catenin, but negative
      for N-cadherin. The other cases were positive for the three molecules examined.
      These results suggest that loss of the N-cadherin expression might associate with
      the spreading of CPC cells. 

PMID- 25373882
TI  - Further characterization of diabetes mellitus and body weight loss in males of
      the congenic mouse strain DDD.Cg-A(y.).
AB  - The A(y) allele at the agouti locus causes obesity and promotes linear growth in
      mice. However, body weight gain stops between 16 and 17 weeks after birth, and
      then, body weight decreases gradually in DDD.Cg-A(y) male mice. Body weight loss
      is a consequence of diabetes mellitus, which is genetically controlled mainly by
      a quantitative trait locus (QTL) on chromosome 4. This study aimed to further
      characterize diabetes mellitus and body weight loss in DDD.Cg-A(y) males. The
      number of beta-cells was markedly reduced, and plasma insulin levels were very
      low in the DDD.Cg-A(y) males. Using a backcross progeny of DDD * (B6 * DDD.Cg
      A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on
      distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower
      body weight. The DDD allele was associated with decreased plasma insulin levels.
      When the DDD.Cg-A(y) males were housed under three different housing conditions
      [group housing (4 or 5 DDD.Cg-A(y) and DDD males), individual housing (single
      DDD.Cg-A(y) male) and single male housing with females (single DDD.Cg-A(y) male
      with DDD.Cg-A(y) or DDD females)], diabetes mellitus and body weight loss were
      most severely expressed in individually housed mice. Thus, the severity of
      diabetes and body weight loss in the DDD.Cg-A(y) males was strongly influenced by
      the housing conditions. These results demonstrate that both genetic and
      nongenetic environmental factors are involved in the development of diabetes
      mellitus and body weight loss in the DDD.Cg-A(y) males. 

PMID- 25373884
TI  - Measurement of anti-TNF agents and anti-drug antibodies serum levels in patients
      with inflammatory bowel disease.
AB  - Despite its undoubted benefit in patients with inflammatory bowel disease, anti
      TNF therapy has some limitations including the lack of primary response and the
      loss of response to treatment in some patients. An empirical approach to these
      problems is frequently used based on clinical outcome. The measurement of anti
      TNF drug serum levels and anti-drug antibodies (ADAb) levels has been proposed
      for improving the management of anti-TNF drugs. Although their role in routine
      clinical practice has not been clearly defined, current data support their
      relationship with clinical outcomes and suggest their clinical utility primarily
      in patients with loss of response to anti-TNF agents. The presence of pre
      existing ADAb before starting the anti-TNF therapy has recently been described.
      Transient ADAb, non-neutralizing ADAb and some cut-offs points have been
      proposed, extending the knowledge about this topic. A standardized and widely
      available test with cut-off points for each anti-TNF agent and the definition of
      the most appropriate actions to be taken given the serum concentration of the
      drugs and ADAb are needed before recommending their routine use. 

PMID- 25373881
TI  - Feasibility of radial and circumferential strain analysis using 2D speckle
      tracking echocardiography in cats.
AB  - The purpose of the present study is to investigate the feasibility of strain
      analysis using speckle tracking echocardiography (STE) in cats and to evaluate
      STE variables in cats with hypertrophic cardiomyopathy (HCM). Sixteen clinically
      healthy cats and 17 cats with HCM were used. Radial and circumferential strain
      and strain rate variables in healthy cats were measured using STE to assess the
      feasibility. Comparisons of global strain and strain variables between healthy
      cats and cats with HCM were performed. Segmental assessments of left ventricle
      (LV) wall for strain and strain rate variables in cats with HCM were also
      performed. As a result, technically adequate images were obtained in 97.6% of the
      segments for STE analysis. Sedation using buprenorphine and acepromazine did not
      affect any global strain nor strain rate variable. In LV segments of cats with
      HCM, reduced segmental radial strain and strain rate variables had significantly
      related with segmental LV hypertrophy. It is concluded that STE analysis using
      short axis images of LV appeared to be clinically feasible in cats, having the
      possibility to be useful for detecting myocardial dysfunctions in cats with
      diseased heart. 

PMID- 25373885
TI  - Twelve tips for teaching social determinants of health in medicine.
AB  - BACKGROUND: There has been a recent movement towards social accountability in
      medical schools, which includes integrating the social, economic, and cultural
      determinants of health into the curriculum. Medical schools and their guiding
      bodies have met this challenge of educating future physicians to provide
      effective care to diverse populations with varying response and successes.
      Because these topics have not been systematically taught in most medical school
      curricula, strategies are needed to teach them alongside clinical sciences. AIM
      AND METHOD: We provide 12 tips on how to teach social determinants of health and
      cultural competency to undergraduate medical students. These recommendations are
      based on a review of the literature and our experience in developing and
      delivering a longitudinal course over the last five years. CONCLUSION: Medical
      students must be taught to think critically about the social and cultural issues
      impacting health, and the intersection with the basic biology and clinical
      skills. Teaching social determinants of health in medicine requires keeping the
      material concrete and applicable. Educators must engage students in active
      learning strategies, reflection, and focus on how to make the material relevant
      to the clinical care of patients.

PMID- 25373883
TI  - Astragalus and Paeoniae radix rubra extract inhibits liver fibrosis by modulating
      the transforming growth factor-beta/Smad pathway in rats.
AB  - It has been previously demonstrated that Astragalus and Paeoniae radix rubra
      extract (APE) had a protective effect against liver fibrosis in mice. The present
      study aimed to investigate the hepatoprotective effect of APE on CCl4-induced
      hepatic fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats
      by intraperitoneal injection of 50% CCl4 twice a week for eight weeks. Organ
      coefficients, serum aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), hexadecenoic acid (HA), laminin (LN), procollagen type III (PCIII),
      hydroxyproline (Hyp), glutathione (GSH-Px), malondialdehyde (MDA), superoxide
      dismutase (SOD) and transforming growth factor beta1 (TGF-beta1) levels were
      measured in rats with hepatic fibrosis. Histopathological changes in affected
      livers were studied using hematoxylin-eosin and Masson's trichrome staining. The
      expression of transforming growth factor-beta/Smad pathway proteins, alpha-smooth
      muscle actin (alpha-SMA), collagen I and collagen III was observed in fibrotic
      livers using western blot analysis. The present study observed significant
      reductions in serum levels of AST, ALT, HA, LN, PCIII and Hyp in APE-treated (2.6
      and 5.2 g/kg) rats, indicating the significant hepatoprotective effects of APE.
      Furthermore, the depletion of GSH-Px and SOD, in addition to the accumulation of
      MDA in liver tissue was suppressed by APE (2.6 and 5.2 g/kg). Pathological
      assessment of CCl4-induced fibrotic livers revealed a significant reduction of
      liver injury and development of hepatic fibrosis in rats treated with APE (2.6
      and 5.2 g/kg). Moreover, APE (2.6 and 5.2 g/kg) decreased the elevation of TGF
      beta1, alpha-SMA, collagen I and collagen III expression, inhibited Smad2/3
      phosphorylation as well as elevated the expression of the TGF-beta1 inhibitor
      Smad7. These results suggested that APE may protect against liver damage and
      inhibit the progression of CCl4-induced hepatic fibrosis. The mechanism of action
      of APE is hypothesized to proceed via scavenging free radicals, decreasing TGF
      beta1 levels and blocking of the TGF-beta/Smad signaling pathway.

PMID- 25373886
TI  - Impact of institute and person variables on teachers' conceptions of learning and
      teaching.
AB  - BACKGROUND: Teachers' conceptions of learning and teaching are important for
      faculty development to result in enduring changes in teaching practices. Until
      now, studies on these conceptions have mostly focused on traditional, lecture
      based curricula rather than on small-group student-centred educational formats,
      which are gaining ground worldwide. AIM: To explore which factors predict
      teachers' conceptions in student-centred curricula. METHODS: In two Dutch medical
      schools with 10 and 40 years of student-centred education, teachers were asked to
      fill out the Conceptions of Learning and Teaching (COLT) Questionnaire to assess
      their 'teacher-centredness', 'appreciation of active learning' and 'orientation
      to professional practice'. Next, we quantitatively assessed the relations of
      teachers' conceptions with their personal and occupational characteristics and
      institute. RESULTS: Overall response was 49.4% (N = 319/646). Institute was the
      main predictor for variance in all three scales, and discipline, gender and
      teaching experience significantly explained variance in two of the scales. More
      than 80% of the variance was not explained by these factors. CONCLUSION: Longer
      exposure to a student-centred curriculum was associated with fewer teacher
      centred conceptions, greater 'appreciation of active learning' and stronger
      'orientation towards professional practice'. In line with studies on lecture
      based curricula, discipline, gender and teaching experience also appeared
      important for teachers' conceptions in student-centred curricula. More research
      is necessary to better understand the influence of institute on the three
      teachers' conceptions scales.

PMID- 25373887
TI  - Electrically controlled one-way photon flow in plasmonic nanostructures.
AB  - Photonics is frequently regarded as a potential pathway for substituting current
      solid-state electronics and as a promise for higher-speed all-optical computing.
      The fundamental challenges facing nanophotonics and electronics of the future are
      nanoscale on-chip integration of electronics and photonics with an efficient
      electric field tuning of light propagation, dynamic access to the light sources
      and material parameters of the system, as well as isolation of optical signals
      analogous to that in electronics. Here we suggest a paradigm for a monolithically
      integrated electronic control over the light propagation in nanoscale plasmonic
      waveguides. We theoretically demonstrate that magnetic field induced by the
      direct electric current flowing in metallic constituents of plasmonic
      nanostructures alters the material parameters and thus the optical signal flow.
      We use this principle for the design of an electrically controlled subwavelength
      optical isolator. 

PMID- 25373888
TI  - Utility of auditory steady-state and brainstem responses in age-related hearing
      loss in rats.
AB  - CONCLUSIONS: The results support the idea that auditory steady-state response
      (ASSR) is a more accurate test for studying age-related hearing loss (ARHL) in
      Sprague-Dawley rats. Differences in the rat middle ear may explain the variations
      of the click properties, with a displacement of the energy toward the 8 and 10
      kHz frequencies compared with humans. OBJECTIVES: The purpose of this study was
      to evaluate ARHL in older and younger Sprague-Dawley rats using auditory clicks
      and tone burst with auditory brainstem response (ABR), in addition to ASSR.
      METHODS: This was a prospective cohort study with 50 animals divided into 5
      groups based on their age in months. A total of 100 registers were elicited from
      each one of the 3 auditory measurements systems in an electrically shielded,
      double-walled, sound-treated cabin. Nine frequencies, from 0.5 to 16 kHz were
      analyzed with the auditory steady-state response and compared with the results
      elicited by the clicks and tone-burst ABR. RESULTS: Comparisons between the
      different frequencies showed lower thresholds in those frequencies below 2 kHz,
      independently of their age in months. The ARHL was detected by each one of the
      three auditory measurement systems, but with lower thresholds with the ASSR test.
      Finally, auditory clicks showed better correlations with 8 and 10 kHz elicited by
      ASSR, which was different to what was expected, based on human studies.

PMID- 25373890
TI  - Longitudinal study of the impact of psychological distress symptoms on new-onset
      upper gastrointestinal symptoms in World Trade Center responders.
AB  - OBJECTIVES: Research on the health of workers involved in the cleanup after the
      attack on the World Trade Center (WTC) on September 11, 2001, has documented high
      rates of psychological distress and upper gastrointestinal (GI) symptoms. The
      current article examines the concurrent and longitudinal associations of
      psychological distress with development of new-onset upper GI symptoms in a large
      sample of WTC responders. METHODS: A cohort of 10,953 WTC responders monitored by
      the WTC Health Program participated in the study. Two occupational groups were
      examined, police and nontraditional responders. The cohort was free of upper GI
      symptoms or diagnoses at their first visit (3 years after September 11, 2001).
      Logistic regression was used to analyze the relationships between concurrent and
      preceding psychological distress symptoms of depression, generalized anxiety,
      panic, and probable posttraumatic stress disorder with the development of new
      onset upper GI symptoms at 3-year follow-up (6 years after September 11, 2001).
      RESULTS: Across both occupation groups, psychological distress symptoms at Visit
      1 were significantly related to the development of GI symptoms by Visit 2 (odd
      ratios ranging from 1.9 to 5.4). The results for the concurrent relationships
      were similar. In addition, there were significant dose-response relationships
      between the number of co-occurring psychological distress symptoms at Visits 1
      and 2, and increased new-onset upper GI symptoms at Visit 2. CONCLUSIONS: In this
      large sample of WTC responders, psychological distress symptoms assessed at 3
      years after 9/11 are related to reporting upper GI symptoms 6 years after 9/11.

PMID- 25373889
TI  - Leukocyte beta-adrenergic receptor sensitivity and depression severity in
      patients with heart failure.
AB  - OBJECTIVES: Clinical outcomes are worse for patients with heart failure (HF) and
      elevated depression symptoms. Depression-related sympathoimmune dysregulation may
      be one mechanism leading to poorer HF prognosis. Sympathetically mediated
      adrenergic activity is known to regulate immune activity via beta-adrenergic
      receptors (beta-ARs). However, studies show conflicting relationships between
      leukocyte beta-AR sensitivity and depression symptoms. The aim of this study was
      to determine in patients with HF the relationship of leukocyte beta-AR
      sensitivity with two diverse measures of depression, self-report questionnaire
      versus clinical diagnostic interview. METHODS: Patients with HF (N = 73, mean
      [standard deviation] age = 56.3 [13.0]) completed the Beck Depression Inventory
      1A and a modified Structured Clinical Interview for the DSM-IV. Leukocyte beta-AR
      sensitivity was determined from isoproterenol-stimulated cyclic adenosine
      monophosphate levels; plasma norepinephrine and epinephrine were also assessed.
      RESULTS: Patients with major depression determined by Structured Clinical
      Interview for the DSM-IV had significantly higher beta-AR sensitivity than did
      nondepressed patients (F(6,72) = 9.27, p = .003, eta = 0.12). The Beck Depression
      Inventory-1A revealed a more complex relationship. Minimal, mild, and moderate-to
      severe depression symptom groups had significant differences in beta-AR
      sensitivity (F(7,72) = 7.03, p = .002, eta = 0.18); mild symptoms were associated
      with reduced beta-AR sensitivity and moderate-to-severe symptoms with higher beta
      AR sensitivity compared with patients with minimal depressive symptoms.
      CONCLUSIONS: Clinical depression was associated with elevated beta-AR sensitivity
      in patients with HF. By deconstructing depression measurements, a greater depth
      of information may be garnered to potentially reveal subtypes of depression
      symptoms and their relation to beta-AR sensitivity.

PMID- 25373891
TI  - Ecological momentary assessment of eating episodes in obese adults.
AB  - OBJECTIVE: The context of eating episodes in obesity is poorly understood. This
      study examined emotional, physiological, and environmental correlates of
      pathological and nonpathological eating episodes in a heterogeneous sample of
      obese adults. METHODS: Community-based participants (n = 50; 84% female [n = 42];
      mean [standard deviation] body mass index = 40.3 [8.5]; mean [standard deviation]
      age = 43.0 [11.9]) recorded all eating episodes and their emotional,
      physiological, and environmental correlates via ecological momentary assessment
      for 2 weeks. Generalized estimating equations examined relations between these
      variables and eating episodes characterized by both self-identified loss of
      control (LOC) while eating and overeating (binge eating; BE), LOC only,
      overeating only (OE), and neither LOC nor OE (nonpathological eating). RESULTS:
      Episodes involving loss of control (BE and LOC) were associated with heightened
      preepisode and postepisode negative effects (Wald chi range, 15.67-24.39; p
      values < .001), whereas those involving overeating (BE and OE) were associated
      with the lowest preepisode and postepisode hunger (Wald chi range, 18.14-39.75; p
      values <.001). LOC episodes were followed by heightened postepisode cravings
      (Wald chi = 25.87; p < .001) and were most likely to occur when participants were
      alone (Wald chi = 13.20; p = .004). CONCLUSION: BE and LOC eating were more
      consistently associated with emotional and physiological cues than OE and
      nonpathological eating, whereas most environmental variables did not differ among
      eating episode types. Results support distinctions among the different constructs
      characterizing aberrant eating and may be used to inform interventions for
      obesity and related eating pathology.

PMID- 25373893
TI  - Life satisfaction and bone mineral density among postmenopausal women: cross
      sectional and longitudinal associations.
AB  - OBJECTIVE: The purpose of this study was to determine whether and how global life
      satisfaction is associated with bone mineral density (BMD) and bone loss.
      METHODS: A total of 2167 women from a cohort of Finnish women born in 1932 to
      1941 were included in the cross-sectional and 1147 women in the 10-year
      longitudinal part of the present study. Participants responded to a postal
      enquiry and underwent femoral BMD densitometry in 1999 (baseline) and 2009
      (follow-up). During the follow-up, their life satisfaction was repeatedly
      measured using a four-item scale. Self-reported data on health, life-style, and
      medication were used to adjust the multivariate linear regression models.
      RESULTS: Mean (standard deviation) femoral BMD decreased over the 10-year follow
      up from 880 (125) to 846 (122) mg/cm. In the multivariate model, life
      satisfaction (p = .028) and its improvement (p = .001) predicted reduced bone
      loss, whereas hospitalization due to depression predicted increased bone loss (B
      = -0.523 annual % change, standard error = 0.212, p = .014). These effects were
      independent of each other. CONCLUSIONS: Easily assessed global life satisfaction
      should be taken into account when effects of aging and prevention of osteoporosis
      as well as health promotion in postmenopausal women are considered.

PMID- 25373892
TI  - Associations between depression and anxiety symptoms and retinal vessel caliber
      in adolescents and young adults.
AB  - OBJECTIVE: Previous longitudinal studies suggest that depression and anxiety are
      associated with risk for cardiovascular disease. The aim of the present study was
      to test whether an association between depression and anxiety symptoms and
      retinal vessel caliber, an indicator of subclinical cardiovascular risk, is
      apparent as early as adolescence and young adulthood. METHODS: Participants were
      865 adolescents and young adults who participated in the Brisbane Longitudinal
      Twin Study and the Twin Eye Study in Tasmania. Participants completed an
      assessment of depression/anxiety symptoms (the Somatic and Psychological Health
      Report) when they were 16.5 years old (mean age), and they underwent retinal
      imaging, on average, 2.5 years later (range, 2 years before to 7 years after the
      depression/anxiety assessment). Retinal vessel caliber was assessed using
      computer software. RESULTS: Depression and anxiety symptoms were associated with
      wider retinal arteriolar caliber in this sample of adolescents and young adults
      (beta = 0.09, p = .016), even after adjusting for other cardiovascular risk
      factors (beta = 0.08, p = .025). Multiple regression analyses revealed that
      affective symptoms of depression/anxiety were associated with retinal vessel
      caliber independently of somatic symptoms. CONCLUSIONS: Depression and anxiety
      symptoms are associated with measurable signs in the retinal microvasculature in
      early life, suggesting that pathological microvascular mechanisms linking
      depression/anxiety and cardiovascular disease may be operative from a young age.

PMID- 25373894
TI  - Post-myocardial infarction anxiety or depressive symptoms and risk of new
      cardiovascular events or death: a population-based longitudinal study.
AB  - OBJECTIVE: To examine the association between anxiety symptoms 3 months after
      myocardial infarction (MI) and/or new cardiovascular events and death, taking
      into account established risk factors, and to compare the results with those of
      the impact of depressive symptoms. Post-MI anxiety symptoms have been associated
      with a composite outcome of new cardiovascular events or death, but previous
      studies have not fully adjusted for potential confounders. It remains unclear
      whether anxiety symptoms are independently associated with both new
      cardiovascular events and death. METHODS: A population-based cohort study of 896
      persons (70% of eligible) with first-time MI between 1 January 2009 and 31
      December 2009, completing the Hospital Anxiety and Depression Scale, were
      followed up until 31 July 2012. RESULTS: A total of 239 new cardiovascular events
      and 94 deaths occurred during 1975 person-years of follow-up. Cox proportional
      hazards models showed that anxiety symptoms were associated with both new
      cardiovascular events and death in analysis adjusted for age only. The estimates
      decreased when adjusted for dyspnea score, physical activity, and depressive
      symptoms, and anxiety symptoms were no longer associated with new cardiovascular
      events (hazard ratio [HR] = 1.02, 95% confidence interval [CI] = 0.98-1.07) or
      with death (HR = 0.94, 95% CI = 0.88-1.01). In fully adjusted models, depressive
      symptoms remained associated with death (HR = 1.13, 95% CI = 1.05-1.21), but not
      with new cardiovascular events (HR = 1.02, 95% CI = 0.99-1.06). CONCLUSIONS: Post
      MI anxiety symptoms were not an independent prognostic risk factor for new
      cardiovascular events or for death, whereas depressive symptoms were associated
      with an increased risk of mortality.

PMID- 25373895
TI  - Uptake of liquid from wet surfaces by the brush-tipped proboscis of a butterfly.
AB  - This study investigated the effect of the brush-tipped proboscis of the Asian
      comma (Polygonia c-aureum) on wet-surface feeding. The tip region of this
      proboscis was observed, especially two microstructures; the intake slits through
      which liquid passes into the proboscis and the brush-like sensilla styloconica.
      The sensilla styloconica were connected laterally to the intake slits in the tip
      region. The liquid-feeding flow between the proboscis and the wet surface was
      measured by micro-particle image velocimetry. During liquid feeding, the sensilla
      styloconica region accumulates liquid by pinning the air-liquid interface to the
      tips of the sensilla styloconica, thus the intake slit region remains immersed.
      The film flow that passes through the sensilla styloconica region shows a
      parabolic velocity profile, and the corresponding flow rate is proportional to
      the cubed length of the sensilla styloconica. Based on these observations, we
      demonstrated that the sensilla styloconica promotes the uptake of liquid from wet
      surfaces. This study may inspire the development of a microfluidic device to
      collect liquid from moist substrates. 

PMID- 25373896
TI  - Antivirulence properties of an antifreeze protein.
AB  - As microbial drug-resistance increases, there is a critical need for new classes
      of compounds to combat infectious diseases. The Ixodes scapularis tick antifreeze
      glycoprotein, IAFGP, functions as an antivirulence agent against diverse
      bacteria, including methicillin-resistant Staphylococcus aureus. Recombinant
      IAFGP and a peptide, P1, derived from this protein bind to microbes and alter
      biofilm formation. Transgenic iafgp-expressing flies and mice challenged with
      bacteria, as well as wild-type animals administered P1, were resistant to
      infection, septic shock, or biofilm development on implanted catheter tubing.
      These data show that an antifreeze protein facilitates host control of bacterial
      infections and suggest therapeutic strategies for countering pathogens. 

PMID- 25373898
TI  - Cdh5/VE-cadherin promotes endothelial cell interface elongation via cortical
      actin polymerization during angiogenic sprouting.
AB  - Organ morphogenesis requires the coordination of cell behaviors. Here, we have
      analyzed dynamic endothelial cell behaviors underlying sprouting angiogenesis in
      vivo. Two different mechanisms contribute to sprout outgrowth: tip cells show
      strong migratory behavior, whereas extension of the stalk is dependent upon cell
      elongation. To investigate the function of Cdh5 in sprout outgrowth, we generated
      null mutations in the zebrafish cdh5 gene, and we found that junctional
      remodeling and cell elongation are impaired in mutant embryos. The defects are
      associated with a disorganization of the actin cytoskeleton and cannot be rescued
      by expression of a truncated version of Cdh5. Finally, the defects in junctional
      remodeling can be phenocopied by pharmacological inhibition of actin
      polymerization, but not by inhibiting actin-myosin contractility. Taken together,
      our results support a model in which Cdh5 organizes junctional and cortical actin
      cytoskeletons, as well as provides structural support for polymerizing F-actin
      cables during endothelial cell elongation. 

PMID- 25373897
TI  - Energy stress regulates hippo-YAP signaling involving AMPK-mediated regulation of
      angiomotin-like 1 protein.
AB  - Hippo signaling is a tumor-suppressor pathway involved in organ size control and
      tumorigenesis through the inhibition of YAP and TAZ. Here, we show that energy
      stress induces YAP cytoplasmic retention and S127 phosphorylation and inhibits
      YAP transcriptional activity and YAP-dependent transformation. These effects
      require the central metabolic sensor AMP-activated protein kinase (AMPK) and the
      upstream Hippo pathway components Lats1/Lats2 and angiomotin-like 1 (AMOTL1).
      Furthermore, we show that AMPK directly phosphorylates S793 of AMOTL1. AMPK
      activation stabilizes and increases AMOTL1 steady-state protein levels,
      contributing to YAP inhibition. The phosphorylation-deficient S793Ala mutant of
      AMOTL1 showed a shorter half-life and conferred resistance to energy-stress
      induced YAP inhibition. Our findings link energy sensing to the Hippo-YAP pathway
      and suggest that YAP may integrate spatial (contact inhibition), mechanical, and
      metabolic signals to control cellular proliferation and survival. 

PMID- 25373899
TI  - In vivo tissue-wide synchronization of mitochondrial metabolic oscillations.
AB  - Little is known about the spatiotemporal coordination of mitochondrial metabolism
      in multicellular organisms in situ. Using intravital microscopy in live animals,
      we report that mitochondrial metabolism undergoes rapid and periodic oscillations
      under basal conditions. Notably, mitochondria in vivo behave as a network of
      functionally coupled oscillators, which maintain a high level of coordination
      throughout the tissue via the activity of gap junctions. These findings reveal a
      unique aspect of the relationship between tissue architecture and self
      organization of mitochondrial metabolism in vivo. 

PMID- 25373901
TI  - Tight coordination of growth and differentiation between germline and soma
      provides robustness for drosophila egg development.
AB  - Organs often need to coordinate the growth of distinct tissues during their
      development. Here, we analyzed the coordination between germline cysts and the
      surrounding follicular epithelium during Drosophila oogenesis. Genetic
      manipulations of the growth rate of both germline and somatic cells influence the
      growth of the other tissue accordingly. Growth coordination is therefore ensured
      by a precise, two-way, intrinsic communication. This coordination tends to
      maintain constant epithelial cell shape, ensuring tissue homeostasis. Moreover,
      this intrinsic growth coordination mechanism also provides cell differentiation
      synchronization. Among growth regulators, PI3-kinase and TORC1 also influence
      differentiation timing cell-autonomously. However, these two pathways are not
      regulated by the growth of the adjacent tissue, indicating that their function
      reflects an extrinsic and systemic influence. Altogether, our results reveal an
      integrated and particularly robust mechanism ensuring the spatial and temporal
      coordination of tissue size, cell size, and cell differentiation for the proper
      development of two adjacent tissues. 

PMID- 25373900
TI  - Mechanosensitive neurons on the internal reproductive tract contribute to egg
      laying-induced acetic acid attraction in Drosophila.
AB  - Selecting a suitable site to deposit their eggs is an important reproductive need
      of Drosophila females. Although their choosiness toward egg-laying sites is well
      documented, the specific neural mechanism that activates females' search for
      attractive egg-laying sites is not known. Here, we show that distention and
      contraction of females' internal reproductive tract triggered by egg delivery
      through the tract plays a critical role in activating such search. We found that
      females start to exhibit acetic acid (AA) attraction prior to depositing each egg
      but no attraction when they are not laying eggs. Artificially distending the
      reproductive tract triggers AA attraction in non-egg-laying females, whereas
      silencing the mechanosensitive neurons we identified that can sense the
      contractile status of the tract eliminates such attraction. Our work uncovers the
      circuit basis of an important reproductive need of Drosophila females and
      provides a simple model for dissecting the neural mechanism that underlies a
      reproductive need-induced behavioral modification. 

PMID- 25373902
TI  - Nonclassical Ly6C(-) monocytes drive the development of inflammatory arthritis in
      mice.
AB  - Different subsets and/or polarized phenotypes of monocytes and macrophages may
      play distinct roles during the development and resolution of inflammation. Here,
      we demonstrate in a murine model of rheumatoid arthritis that nonclassical Ly6C(
      ) monocytes are required for the initiation and progression of sterile joint
      inflammation. Moreover, nonclassical Ly6C(-) monocytes differentiate into
      inflammatory macrophages (M1), which drive disease pathogenesis and display
      plasticity during the resolution phase. During the development of arthritis,
      these cells polarize toward an alternatively activated phenotype (M2), promoting
      the resolution of joint inflammation. The influx of Ly6C(-) monocytes and their
      subsequent classical and then alternative activation occurs without changes in
      synovial tissue-resident macrophages, which express markers of M2 polarization
      throughout the course of the arthritis and attenuate joint inflammation during
      the initiation phase. These data suggest that circulating Ly6C(-) monocytes
      recruited to the joint upon injury orchestrate the development and resolution of
      autoimmune joint inflammation. 

PMID- 25373903
TI  - Hypothalamic PGC-1alpha protects against high-fat diet exposure by regulating
      ERalpha.
AB  - High-fat diets (HFDs) lead to obesity and inflammation in the central nervous
      system (CNS). Estrogens and estrogen receptor alpha (ERalpha) protect
      premenopausal females from the metabolic complications of inflammation and
      obesity-related disease. Here, we demonstrate that hypothalamic PGC-1alpha
      regulates ERalpha and inflammation in vivo. HFD significantly increased palmitic
      acid (PA) and sphingolipids in the CNS of male mice when compared to female mice.
      PA, in vitro, and HFD, in vivo, reduced PGC-1alpha and ERalpha in hypothalamic
      neurons and astrocytes of male mice and promoted inflammation. PGC-1alpha
      depletion with ERalpha overexpression significantly inhibited PA-induced
      inflammation, confirming that ERalpha is a critical determinant of the anti
      inflammatory response. Physiologic relevance of ERalpha-regulated inflammation
      was demonstrated by reduced myocardial function in male, but not female, mice
      following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1alpha
      and ERalpha, promoting inflammation and decrements in myocardial function in a
      sex-specific way. 

PMID- 25373904
TI  - Glutamate acts as a key signal linking glucose metabolism to incretin/cAMP action
      to amplify insulin secretion.
AB  - Incretins, hormones released by the gut after meal ingestion, are essential for
      maintaining systemic glucose homeostasis by stimulating insulin secretion. The
      effect of incretins on insulin secretion occurs only at elevated glucose
      concentrations and is mediated by cAMP signaling, but the mechanism linking
      glucose metabolism and cAMP action in insulin secretion is unknown. We show here,
      using a metabolomics-based approach, that cytosolic glutamate derived from the
      malate-aspartate shuttle upon glucose stimulation underlies the stimulatory
      effect of incretins and that glutamate uptake into insulin granules mediated by
      cAMP/PKA signaling amplifies insulin release. Glutamate production is diminished
      in an incretin-unresponsive, insulin-secreting beta cell line and pancreatic
      islets of animal models of human diabetes and obesity. Conversely, a membrane
      permeable glutamate precursor restores amplification of insulin secretion in
      these models. Thus, cytosolic glutamate represents the elusive link between
      glucose metabolism and cAMP action in incretin-induced insulin secretion. 

PMID- 25373906
TI  - The tumor suppressor Smad4/DPC4 is regulated by phosphorylations that integrate
      FGF, Wnt, and TGF-beta signaling.
AB  - Smad4 is a major tumor suppressor currently thought to function constitutively in
      the transforming growth factor beta (TGF-beta)-signaling pathway. Here, we report
      that Smad4 activity is directly regulated by the Wnt and fibroblast growth factor
      (FGF) pathways through GSK3 and mitogen-activated protein kinase (MAPK)
      phosphorylation sites. FGF activates MAPK, which primes three sequential GSK3
      phosphorylations that generate a Wnt-regulated phosphodegron bound by the
      ubiquitin E3 ligase beta-TrCP. In the presence of FGF, Wnt potentiates TGF-beta
      signaling by preventing Smad4 GSK3 phosphorylations that inhibit a
      transcriptional activation domain located in the linker region. When MAPK is not
      activated, the Wnt and TGF-beta signaling pathways remain insulated from each
      other. In Xenopus embryos, these Smad4 phosphorylations regulate germ-layer
      specification and Spemann organizer formation. The results show that three major
      signaling pathways critical in development and cancer are integrated at the level
      of Smad4. 

PMID- 25373905
TI  - ESCRT-II/Vps25 constrains digit number by endosome-mediated selective modulation
      of FGF-SHH signaling.
AB  - Sorting and degradation of receptors and associated signaling molecules maintain
      homeostasis of conserved signaling pathways during cell specification and tissue
      development. Yet, whether machineries that sort signaling proteins act
      preferentially on different receptors and ligands in different contexts remains
      mysterious. Here, we show that Vacuolar protein sorting 25, Vps25, a component of
      ESCRT-II (Endosomal Sorting Complex Required for Transport II), directs
      preferential endosome-mediated modulation of FGF signaling in limbs. By ENU
      induced mutagenesis, we isolated a polydactylous mouse line carrying a
      hypomorphic mutation of Vps25 (Vps25(ENU)). Unlike Vps25-null embryos we
      generated, Vps25(ENU/ENU) mutants survive until late gestation. Their limbs
      display FGF signaling enhancement and consequent hyperactivation of the FGF-SHH
      feedback loop causing polydactyly, whereas WNT and BMP signaling remain
      unperturbed. Notably, Vps25(ENU/ENU) Mouse Embryonic Fibroblasts exhibit aberrant
      FGFR trafficking and degradation; however, SHH signaling is unperturbed. These
      studies establish that the ESCRT-II machinery selectively limits FGF signaling in
      vertebrate skeletal patterning. 

PMID- 25373907
TI  - Cellular heterogeneity in the mouse esophagus implicates the presence of a
      nonquiescent epithelial stem cell population.
AB  - Because the esophageal epithelium lacks a defined stem cell niche, it is unclear
      whether all basal epithelial cells in the adult esophagus are functionally
      equivalent. In this study, we showed that basal cells in the mouse esophagus
      contained a heterogeneous population of epithelial cells, similar to other
      rapidly cycling tissues such as the intestine or skin. Using a combination of
      cell-surface markers, we separated primary esophageal tissue into distinct cell
      populations that harbored differences in stem cell potential. We also used an in
      vitro 3D organoid assay to demonstrate that Sox2, Wnt, and bone morphogenetic
      protein signaling regulate esophageal self-renewal. Finally, we labeled
      proliferating basal epithelial cells in vivo to show differing cell-cycle
      profiles and proliferation kinetics. Based on our results, we propose that a
      nonquiescent stem cell population resides in the basal epithelium of the mouse
      esophagus. 

PMID- 25373909
TI  - Rhythmic degradation explains and unifies circadian transcriptome and proteome
      data.
AB  - The rich mammalian cellular circadian output affects thousands of genes in many
      cell types and has been the subject of genome-wide transcriptome and proteome
      studies. The results have been enigmatic because transcript peak abundances do
      not always follow the peaks of gene-expression activity in time. We posited that
      circadian degradation of mRNAs and proteins plays a pivotal role in setting their
      peak times. To establish guiding principles, we derived a theoretical framework
      that fully describes the amplitudes and phases of biomolecules with circadian
      half-lives. We were able to explain the circadian transcriptome and proteome
      studies with the same unifying theory, including cases in which transcripts or
      proteins appeared before the onset of increased production rates. Furthermore, we
      estimate that 30% of the circadian transcripts in mouse liver and Drosophila
      heads are affected by rhythmic posttranscriptional regulation. 

PMID- 25373910
TI  - Comprehensive identification of host modulators of HIV-1 replication using
      multiple orthologous RNAi reagents.
AB  - RNAi screens have implicated hundreds of host proteins as HIV-1 dependency
      factors (HDFs). While informative, these early studies overlap poorly due to
      false positives and false negatives. To ameliorate these issues, we combined
      information from the existing HDF screens together with new screens performed
      with multiple orthologous RNAi reagents (MORR). In addition to being
      traditionally validated, the MORR screens and the historical HDF screens were
      quantitatively integrated by the adaptation of an established analysis program,
      RIGER, for the collective interpretation of each gene's phenotypic significance.
      False positives were addressed by the removal of poorly expressed candidates
      through gene expression filtering, as well as with GESS, which identifies off
      target effects. This workflow produced a quantitatively integrated network of
      genes that modulate HIV-1 replication. We further investigated the roles of
      GOLGI49, SEC13, and COG in HIV-1 replication. Collectively, the MORR-RIGER method
      minimized the caveats of RNAi screening and improved our understanding of HIV-1
      host cell interactions. 

PMID- 25373908
TI  - Mapping the interaction sites between AMPA receptors and TARPs reveals a role for
      the receptor N-terminal domain in channel gating.
AB  - AMPA-type glutamate receptors (AMPARs) mediate fast neurotransmission at
      excitatory synapses. The extent and fidelity of postsynaptic depolarization
      triggered by AMPAR activation are shaped by AMPAR auxiliary subunits, including
      the transmembrane AMPAR regulatory proteins (TARPs). TARPs profoundly influence
      gating, an effect thought to be mediated by an interaction with the AMPAR ion
      channel and ligand binding domain (LBD). Here, we show that the distal N-terminal
      domain (NTD) contributes to TARP modulation. Alterations in the NTD-LBD linker
      result in TARP-dependent and TARP-selective changes in AMPAR gating. Using
      peptide arrays, we identify a TARP interaction region on the NTD and define the
      path of TARP contacts along the LBD surface. Moreover, we map key binding sites
      on the TARP itself and show that mutation of these residues mediates gating
      modulation. Our data reveal a TARP-dependent allosteric role for the AMPAR NTD
      and suggest that TARP binding triggers a drastic reorganization of the AMPAR
      complex. 

PMID- 25373911
TI  - Large-scale identification of coregulated enhancer networks in the adult human
      brain.
AB  - Understanding the complexity of the human brain and its functional diversity
      remain a major challenge. Distinct anatomical regions are involved in an array of
      processes, including organismal homeostasis, cognitive functions, and
      susceptibility to neurological pathologies, many of which define our species.
      Distal enhancers have emerged as key regulatory elements that acquire histone
      modifications in a cell- and species-specific manner, thus enforcing specific
      gene expression programs. Here, we survey the epigenomic landscape of promoters
      and cis-regulatory elements in 136 regions of the adult human brain. We identify
      a total of 83,553 promoter-distal H3K27ac-enriched regions showing global
      characteristics of brain enhancers. We use coregulation of enhancer elements
      across many distinct regions of the brain to uncover functionally distinct
      networks at high resolution and link these networks to specific neuroglial
      functions. Furthermore, we use these data to understand the relevance of
      noncoding genomic variations previously linked to Parkinson's disease incidence. 

PMID- 25373912
TI  - Sox17-mediated XEN cell conversion identifies dynamic networks controlling cell
      fate decisions in embryo-derived stem cells.
AB  - Little is known about the gene regulatory networks (GRNs) distinguishing
      extraembryonic endoderm (ExEn) stem (XEN) cells from those that maintain the
      extensively characterized embryonic stem cell (ESC). An intriguing network
      candidate is Sox17, an essential transcription factor for XEN derivation and self
      renewal. Here, we show that forced Sox17 expression drives ESCs toward ExEn,
      generating XEN cells that contribute to ExEn when placed back into early mouse
      embryos. Transient Sox17 expression is sufficient to drive this fate change
      during which time cells transit through distinct intermediate states prior to the
      generation of functional XEN-like cells. To orchestrate this conversion process,
      Sox17 acts in autoregulatory and feedforward network motifs, regulating dynamic
      GRNs directing cell fate. Sox17-mediated XEN conversion helps to explain the
      regulation of cell-fate changes and reveals GRNs regulating lineage decisions in
      the mouse embryo. 

PMID- 25373914
TI  - Non-viral immune electrogene therapy induces potent antitumour responses and has
      a curative effect in murine colon adenocarcinoma and melanoma cancer models.
AB  - Antitumour efficacy of electroporated pEEV, coding for granulocyte-macrophage
      colony-stimulating factor and the B7-1 costimulatory immune molecule (pEEVGmCSF
      b7.1) in growing solid tumours, was investigated and compared with a standard
      plasmid. Application of pEEVGmCSF-b7.1 led to complete tumour regression in 66%
      of CT26-treated tumours and 100% in the B16F10-treated tumours at day 150 post
      treatment. pEEVGmCSF-b7.1 treatment was found to significantly enhance levels of
      both innate and adaptive immune populations in tumour and systemic sites, which
      corresponded to significantly increased tissue levels of proinflammatory
      cytokines including interferon-gamma (IFN-gamma) and interleukin-12 (IL-12). In
      contrast, pEEVGmCSF-b7.1 treatment significantly reduced the T-regulatory
      populations and also the anti-inflammatory cytokine IL-10. Upon further
      characterisation of functional immune responses, we observed a significant
      increase in cytotoxic (CD107a+) and IFN-gamma-producing natural killer cells and
      also significantly more in IL-12-producing B cells. Importantly, splenocytes
      isolated from pEEVGmCSF-b7.1-treated 'cured' mice were tumour-specific and
      afforded significant protection in a tumour rechallenge model (Winn assay). Our
      data indicate that electroimmunogene therapy with the non-viral pEEVGmCSF-b7.1 is
      able to induce potent and durable antitumour immune responses that significantly
      reduce primary and also secondary tumour growth, and thus represents a solid
      therapeutic platform for pursuing future clinical trials. 

PMID- 25373915
TI  - Acanthoic acid inhibits LPS-induced inflammatory response in human gingival
      fibroblasts.
AB  - Periodontitis is a chronic disease that affects the gums and destroys connective
      tissue. Acanthoic acid (AA), a diterpene in Acanthopanax koreanum, has been
      reported to have anti-inflammatory activities. The aim of this study was to
      investigate the anti-inflammatory effects of AA on lipopolysaccharide (LPS)
      induced inflammatory response in human gingival fibroblasts (HGFs). HGFs were
      treated with Porphyromonas gingivalis LPS in the presence or absence of AA. The
      production of inflammatory cytokines IL-8 and IL-6 were measured by ELISA. The
      expression of NF-kappaB and TLR4 were detected by Western blotting. The results
      showed that AA inhibited LPS-induced IL-8 and IL-6 production in a dose-dependent
      manner. In addition, AA inhibited LPS-induced TLR4 expression and NF-kappaB
      activation. In conclusion, AA inhibits LPS-induced inflammatory response in HGFs
      through inhibition TLR4-mediated NF-kappaB signaling pathway. 

PMID- 25373916
TI  - Anti-inflammatory effects of cavidine in vitro and in vivo, a selective COX-2
      inhibitor in LPS-induced peritoneal macrophages of mouse.
AB  - Cavidine is an isoquinoline alkaloid which is isolated from Corydalis impatiens.
      In traditional Tibetan herb, C. impatiens has been widely used for treatment of
      skin injuries, hepatitis, cholecystitis, and scabies. The present study aimed to
      evaluate its anti-inflammatory effect and investigate the mechanisms underlying
      this anti-inflammatory action. We used different inflammation model animals and
      lipopolysaccharide (LPS)-induced murine peritoneal macrophages to examine the
      anti-inflammatory function of cavidine. Results indicated pretreatment with
      cavidine (i.p.) decreased xylene-induced ear edema, formaldehyde-induced paw
      edema, leukocyte number, and the level of nitric oxide (NO), prostaglandin E2
      (PGE2), and tumor necrosis factor-alpha (TNF-alpha) in acetic acid-induced
      peritonitis in mice. The data also demonstrated that cavidine significantly
      inhibited LPS-induced TNF-alpha, interleukin-6 (IL-6), and NO production in
      peritoneal macrophages. Moreover, cavidine regulated the expression of
      cyclooxygenase-2 (COX-2) instead of cyclooxygenase-1 (COX-1) at protein levels.
      These results suggested that cavidine is a selective COX-2 inhibitor which
      possesses an anti-inflammatory activity. 

PMID- 25373917
TI  - Ultra-rapid prototyping of flexible, multi-layered microfluidic devices via razor
      writing.
AB  - The fabrication of microfluidic devices is often still a time-consuming and
      costly process. Here we introduce a very simple and cheap microfabrication
      process based on "razor writing", also termed xurography, for the ultra-rapid
      prototyping of microfluidic devices. Thin poly(dimethylsiloxane) (PDMS) membranes
      are spin-coated on flexible plastic foil and cut into user-defined shapes with a
      bench-top cutter plotter. The PDMS membranes can then be assembled into desirable
      microdevices via plasma bonding. The plastic foil allows manipulation of
      exceptionally thin (30-300 MUm) PDMS layers and can be readily peeled after
      fabrication. This versatile technique can be used to produce a wide variety of
      microfluidic device prototypes within just a few hours. 

PMID- 25373919
TI  - Synthesizing AND gate genetic circuits based on CRISPR-Cas9 for identification of
      bladder cancer cells.
AB  - The conventional strategy for cancer gene therapy offers limited control of
      specificity and efficacy. A possible way to overcome these limitations is to
      construct logic circuits. Here we present modular AND gate circuits based on
      CRISPR-Cas9 system. The circuits integrate cellular information from two
      promoters as inputs and activate the output gene only when both inputs are active
      in the tested cell lines. Using the luciferase reporter as the output gene, we
      show that the circuit specifically detects bladder cancer cells and significantly
      enhances luciferase expression in comparison to the human telomerase reverse
      transcriptase-renilla luciferase construct. We also test the modularity of the
      design by replacing the output with other cellular functional genes including
      hBAX, p21 and E-cadherin. The circuits effectively inhibit bladder cancer cell
      growth, induce apoptosis and decrease cell motility by regulating the
      corresponding gene. This approach provides a synthetic biology platform for
      targeting and controlling bladder cancer cells in vitro. 

PMID- 25373918
TI  - Reduction of endoplasmic reticulum stress inhibits neointima formation after
      vascular injury.
AB  - Endoplasmic reticulum (ER) stress and inappropriate adaptation through the
      unfolded protein response (UPR) are predominant features of pathological
      processes. However, little is known about the link between ER stress and
      endovascular injury. We investigated the involvement of ER stress in neointima
      hyperplasia after vascular injury. The femoral arteries of 7-8-week-old male mice
      were subjected to wire-induced vascular injury. After 4 weeks, immunohistological
      analysis showed that ER stress markers were upregulated in the hyperplastic
      neointima. Neointima formation was increased by 54.8% in X-box binding protein-1
      (XBP1) heterozygous mice, a model of compromised UPR. Knockdown of Xbp1 in human
      coronary artery smooth muscle cells (CASMC) in vitro promoted cell proliferation
      and migration. Furthermore, treatment with ER stress reducers, 4-phenylbutyrate
      (4-PBA) and tauroursodeoxycholic acid (TUDCA), decreased the intima-to-media
      ratio after wire injury by 50.0% and 72.8%, respectively. Chronic stimulation of
      CASMC with PDGF-BB activated the UPR, and treatment with 4-PBA and TUDCA
      significantly suppressed the PDGF-BB-induced ER stress markers in CASMC and the
      proliferation and migration of CASMC. In conclusion, increased ER stress
      contributes to neointima formation after vascular injury, while UPR signaling
      downstream of XBP1 plays a suppressive role. Suppression of ER stress would be a
      novel strategy against post-angioplasty vascular restenosis. 

PMID- 25373920
TI  - Topical analgesics for neuropathic pain in the elderly: current and future
      prospects.
AB  - Neuropathic pain (NeP) is a significant medical and socioeconomic burden with
      limited therapeutic options. Elderly patients exhibit a higher incidence of
      several NeP conditions and pose a particular challenge due to age-related
      pharmacokinetic and pharmacodynamic issues, comorbid conditions, and
      polypharmacy, as well as frailty and cognitive decline. Topical analgesics are of
      interest because of their comparable efficacy to oral agents, good tolerability
      and safety, and potential to be add-on therapies to oral treatments. In recent
      years, two topical formulations for NeP have been approved (5% lidocaine
      medicated plaster, 8% capsaicin patch) but are not available in all countries.
      There are controlled trials and a growing body of open-label reports on their use
      in clinical care. Some studies provide a post hoc analysis of data in relation to
      older age (>=65 years), which is useful. The body of evidence relating to topical
      investigational agents is growing and involves controlled trials as well as
      individual cases. The largest single body of information is for topical ketamine,
      administered either alone or combined with other agents (particularly
      amitriptyline), and some large randomized controlled trials report efficacy.
      Other large trials involve topical clonidine and further ketamine combinations.
      Compounding analgesics involves challenges, including uncertain composition (two
      to five ingredients are used) and concentrations (range 0.5-5%), as well as the
      heterogeneity of data that support choices. Nevertheless, case reports and
      acceptable response rates in larger cohorts are intriguing, and this area merits
      further investigation in controlled settings as well as continued documentation
      of clinical experiences.

PMID- 25373921
TI  - Effective pain management in patients with dementia: benefits beyond pain?
AB  - This current opinion aims to provide a literature overview of the associations
      between pain and neuropsychiatric symptoms and the efficacy of pain management
      for both pain and neuropsychiatric symptoms in patients with dementia. In
      addition, international guidelines and recommendations for pain management have
      been collated, and important developing research areas are highlighted. Pain is,
      in general, under-recognized and undertreated in people with dementia and may
      therefore trigger or exacerbate neuropsychiatric symptoms. While there is an
      abundance of pain assessment instruments intended for people with dementia, few
      have been adequately tested for their feasibility, reliability and validity. In
      patients with dementia, vocalizations, facial expressions and body movements may
      be the only valid expressions of pain. Further, pain has been related to the
      neuropsychiatric symptoms of agitation, aggression, mood syndrome and sleep
      problems. Unfortunately, health personnel may misinterpret these symptoms as
      neuropsychiatric symptoms of dementia. A differential assessment of dementia, its
      presenting neuropsychiatric symptoms and the potential presence of pain is
      crucial to provide the correct treatment. To achieve this, use of pain assessment
      tools that are responsive to change and are validated for use in patients with
      dementia is a prerequisite. To date, there have been few studies, with
      inconsistent findings on the association between pain and neuropsychiatric
      symptoms. To ensure a better differential assessment of pain and neuropsychiatric
      symptoms, and consequently more accurate treatment for patients with dementia,
      studies with adequate statistical power and high-quality study designs, including
      randomized controlled trials, are needed. 

PMID- 25373922
TI  - High prevalence of overweight, obesity, and hypertension with increased risk to
      cardiovascular disorders among adults in northwest Ethiopia: a cross sectional
      study.
AB  - BACKGROUND: Overweight and obesity are components of a defined cluster of risk
      factors for non-communicable diseases, once problems for only the high-income
      countries, in recent days became rampant in developing countries. Despite the
      lack of extensive data on metabolic and cardio vascular disorders in Ethiopia,
      the prevalence of obesity among young adults (15-24 years), in a cross sectional
      study conducted in 1997, was 0.7% for men and 6% for women. The prevalence of
      hypertension (HTN) was found to be 7.1% of the population. The objective of this
      study was to see the prevalence and association of overweight, obesity and HTN
      and to check if there was any agreement among the various anthropometric
      measurements in detecting overweight and obesity. METHODS: This cross-sectional
      study was conducted in Gondar city, Northwest Ethiopia. A total of 68
      participants with age >18 year were randomly selected and included. Data were
      collected using questionnaires and through physical measurements of weight,
      height and blood pressure, using the WHO recommendations. RESULT: The prevalence
      of hypertension was 13.3% (9/68). The prevalence of overweight based on
      calculated body mass index (BMI) was 32.4% (22/68) while the prevalence of
      obesity was 16.2% (11/68). Body fat percentage (BFP) effectively classified all
      of the 'overweight' and 'obese' values according to the BMI as 'overweight/obese'
      (P = 0.016). Risk level classification with waist circumference enabled to
      correctly classify most (90.9%) and all of the 'overweight' and 'obese' BMI
      values as 'increased risk/substantially increased risk' (P < 0.001). Similarly,
      waist-to-height ratio (WHtR) was able to classify all 'overweight' and 'obese'
      BMI values as 'increased risk/substantially increased risk' (P < 0.001).
      CONCLUSION: In conclusion, the current study was able to detect a high prevalence
      of overweight, obesity, and HTN among adult population in Gondar town. There is a
      prevalent high level of general adiposity and central obesity. WHtR and BFP were
      the most efficient measurements to identify all 'high risk' groups of individuals
      as 'high risk' irrespective of their gender. Further study is recommended to
      elucidate the risk factors and complications of obesity and overweight in the
      study area and beyond.

PMID- 25373924
TI  - Involvement of dietary Fatty acids in multiple biological and psychological
      functions, in morbidly obese subjects.
AB  - BACKGROUND: Fatty acid (FA) profile is often altered, in morbidly obese subjects,
      both before and after bariatric surgery. We measured FA plasma levels before and
      6 months after Roux-en-Y gastric bypass (RYGB), in order to evaluate their
      relationship with different biological and psychological parameters and the
      impact of RYGB on the FA plasma levels. METHODS: Thirty eight morbidly obese
      patients were investigated before RYGB, and 28 of them were reexamined 6 months
      postoperatively. Anxiety, depression, and quality of life were evaluated by
      validated questionnaires. Plasma FA (saturated, monounsaturated, polyunsaturated
      omega-6 and omega-3), vitamins A and E, fasting insulinemia, and high-sensitive C
      reactive protein (hs-CRP) were measured. RESULTS: Before surgery, omega-3
      polyunsaturated FA and vit A showed significant negative relationship with
      fasting insulinemia (gamma-linolenic p = 0.03, eicosapentaenoic, vit A p = 0.01)
      and hs-CRP (eicosapentaenoic p = 0.03, vit A p = 0.02) and a positive link with
      HDL cholesterol (gamma-linolenic p = 0.03, vit A p = 0.02). Depression score was
      significantly and negatively linked with palmitoleic (p = 0.03), gamma-linolenic
      (p = 0.006), dihomo-gamma-linolenic (p = 0.02), and alpha-linolenic (p = 0.03)
      acids. After surgery, FA and both vit A and E were significantly reduced. Vit A
      levels were below 2.4 MUmol/l in 63 % of the patients, preoperatively, and in 79
      % after surgery. Preoperative levels of linoleic acid were significantly related
      with the postoperative weight reduction (p = 0.0006). CONCLUSIONS: FA are
      involved in several biological and psychological functions. The RYGB-induced
      reduction of FA could have deleterious consequences on vitamin absorption,
      metabolism, and depression. Thus, the surveillance of FA levels is of primary
      importance both before and after RYGB.

PMID- 25373923
TI  - Advanced age as an independent predictor of perioperative risk after laparoscopic
      sleeve gastrectomy (LSG).
AB  - BACKGROUND: While the safety of many bariatric procedures has been previously
      studied in older patients, we examine the effect of advancing age on
      medical/surgical complications in laparoscopic sleeve gastrectomy, a relatively
      unstudied procedure but that is trending upwards in use. METHODS: Patients
      undergoing laparoscopic sleeve gastrectomy (LSG) and laparoscopic gastric bypass
      (RYGB) were extracted from the National Surgical Quality Improvement Program 2005
      2012 database. Pre- and postoperative variables were analyzed using chi-square
      and student t test as appropriate to determine the comparative safety of LSG to
      RYGB in the elderly. Multivariate regression modeling was used to evaluate
      whether age is associated with adverse 30-day events following LSG. RESULTS: Of
      the patients that met the inclusion criteria, 56,664 (84 %) patients underwent
      RYGB and 10,835 (16 %) underwent LSG. In the LSG cohort, incidence of overall
      complications, medical complications, and death significantly increased with
      increasing age (p < 0.05). No statistically significant differences in rates of
      30-day complications, return to the OR, and mortality exist between RYGB and LSG
      cohorts in patients older than 65 years. The age group of over 65 years
      independently predicted increased risk for overall and medical complications (OR,
      1.748; OR, 2.027). Notably, age was not significantly associated with surgical
      complications in LSG. CONCLUSION: In this large, multi-institutional study,
      advanced age was significantly associated with overall and medical complications
      but not surgical complications in LSG. Our findings suggest that the risk
      conferred by advancing age in LSG is predominantly for medical morbidity and
      advocate for improved perioperative management of medical complications. LSG may
      be the preferable option to RYGB for elderly patients as neither procedure is
      riskier with regards to 30-day morbidity while LSG has been shown to be safer
      with regards to long-term reoperation and readmission risk.

PMID- 25373925
TI  - The effect of insurance status on pre- and post-operative bariatric surgery
      outcomes.
AB  - BACKGROUND: This study compared pre- and post-surgical data and outcomes among
      gastric bypass patients based on the type of insurance (Medicaid, Medicare, or
      private). METHODS: Data were examined from 2553 consecutive RYGB patients at a
      rural ASMBS Center of Excellence. RESULTS: Participants were primarily female
      (80.5 %), Caucasian (97.1 %), and middle-aged (45.9 years). Medicaid patients'
      BMI at consultation was significantly higher than the other two groups (p <
      0.001). Time to surgery was significantly longer for Medicaid (13.2 %) and
      Medicare (7.1 %) patients compared with privately insured patients (p < 0.001).
      Pre-surgical weight loss and post-surgical percent of excess weight loss nadir
      did not differ among the groups. Type 2 diabetes remission rates were comparable
      across insurance groups. CONCLUSIONS: Medicaid patients, although demographically
      different from their privately insured and Medicare counterparts, will benefit
      from surgery with comparable weight loss results and overall diabetes remission
      rates.

PMID- 25373927
TI  - Engaging patients to recover life projectuality: an Italian cross-disease
      framework.
AB  - PURPOSE: Chronic disease is recognized as having a large impact on patient
      quality of life (QoL), which can be defined as an individual's satisfaction or
      happiness with life in domains he or she considers important. Policy makers and
      clinicians recognize increasingly that patients can safeguard their QoL by making
      healthy lifestyle choices and being actively engaged in their health care.
      However, in the emphasis on promoting patient engagement to enhance patients'
      QoL, there is no consensus regarding the relationship between QOL and patient
      engagement, resulting in a lack of shared guidelines among clinicians on
      interventions. Furthermore, no studies have provided an in-depth exploration of
      the perspective of patients with chronic conditions who are engaged in their
      health care and their requirements to achieve an improved QoL. Given this
      theoretical gap, the present study attempted to explore the patient engagement
      experience and its relationship with patient QoL in the context of the Italian
      healthcare system and in relation to different chronic diseases. METHODS: In
      depth qualitative interviews on a sample of 99 patients with a wide variety of
      chronic conditions (heart failure, chronic obstructive pulmonary disease, stroke,
      diabetes, and cancer). RESULTS: Patient engagement in health care can be defined
      as a context-based and cross-disease process that appears to enable patients to
      recover their life projectuality, which had been impaired by the onset of chronic
      disease. Successful patient engagement may also be related to a positive shift in
      the ways in which patients perceive self and life and experience empowerment to
      realize their life potential, thus improving quality of life. Patient engagement
      is a powerful concept capable of reflecting significant psychosocial changes that
      promote patient QoL along the care process. There appears to be theoretical and
      empirical justification for a broad definition of QoL. CONCLUSIONS: QoL deeply
      depends on the patient ability to engage in their care and on the health
      expectations they have. We propose a model of the relation between patient
      engagement and patients' trajectories in critical event responses and use it to
      illustrate a new perspective on QoL. This research showed the heuristic value
      patient engagement as a is a key concept in the promotion of a patients'
      experience-sensitive QoL interventions and assessment measures.

PMID- 25373926
TI  - Intermediate neoadjuvant radiotherapy for T3 low/middle rectal cancer:
      postoperative outcomes of a non-controlled clinical trial.
AB  - BACKGROUND: The benefits of adjuvant radiotherapy in rectal carcinoma are well
      known. However, there is still considerable uncertainty about the optimal
      radiation treatment. There is an ongoing debate about the choice between very
      short treatments immediately followed by surgical resection and prolonged
      treatments with delayed surgery. In this paper, we describe an interim analysis
      of a non-controlled clinical trial in which radiotherapy delivered with
      intermediate dose/duration was followed by surgery after about 2 weeks to improve
      local control and survival after curative radiosurgery for cT3 low/middle rectal
      cancer. METHODS: Preoperative radiotherapy (36 Gy in 3 weeks) was delivered in
      248 consecutive patients with cT3NxM0 rectal adenocarcinoma within 10 cm from the
      anal verge, followed by surgery within the third week after treatment completion.
      RESULTS: 166 patients (66.94%) underwent anterior resection, 80 patients (32.26%)
      the Miles' procedure and 2 patients (0.8%) the Hartmann's procedure. Local
      resectability rate was 99.6%, with 226 curative-intent resections. The overall
      rate of complications was 27.4%. 5-year oncologic outcomes were evaluated on 223
      patients. The median follow-up time was 8.9 years (range 5-17.4 years); local
      recurrence (LR) rate and distal recurrence (DR) rate after 5 years were 6.28% and
      21.97%, respectively. Overall survival was 74.2%; disease free survival was
      73.5%; local control was 93.4 % and metastasis-free survival was 82.1%.
      CONCLUSIONS: preoperative radiotherapy with intermediate dose/duration and
      interval between radiotherapy and surgery achieves high local control in patients
      with cT3NxM0 rectal cancer, and high DR rate seems to be the major limitation to
      improved survival.

PMID- 25373928
TI  - Cultural adaptation and psychometric assessment of Pain Catastrophizing Scale
      among young healthy Malay-speaking adults in military settings.
AB  - PURPOSE: The Pain Catastrophizing Scale (PCS) is designed to assess negative
      thoughts in response to pain. It is composed of three domains: helplessness,
      rumination, and magnification. We report on the translation, adaptation, and
      validation of scores on a Malay-speaking version of the PCS, the PCS-MY. METHOD:
      Guidelines for the process of cross-cultural adaptations of assessment measures
      were implemented. A sample of 303 young military recruits participated in the
      study. Factor structure, reliability, and validity of scores on the PCS-MY were
      examined. Convergent validity was investigated with the Positive and Negative
      Affect Scale, Short-form 12 version 2, and Ryff's Psychological Well-being Scale.
      RESULTS: Most participants were men, ranging in age from 19 to 26. The
      reliability of the PCS-MY scores was adequate (alpha = 0.90; mean inter-item
      correlation = 0.43). Confirmatory factor analysis showed that a modified version
      of the PCS-MY provided best fit estimates to the sample data. The PCS-MY total
      score was negatively correlated with mental well-being and positively correlated
      with negative affect (all ps < 0.001). CONCLUSION: The PCS-MY was demonstrated to
      have adequate reliability and validity estimates in the study sample.

PMID- 25373929
TI  - Hyperthyroidism induced by Graves' disease reversibly affects skin microvascular
      reactivity.
AB  - BACKGROUND: The impact of hyperthyroidism induced by Graves' disease (GD) on skin
      microcirculation has not been established. We aimed to assess vascular reactivity
      in hyperthyroid GD patients before and during treatment. METHODS: Laser Doppler
      flux (LDF) was measured in 31 newly diagnosed hyperthyroid GD patients with an
      increased TSH receptor stimulating antibody (TSAb) levels before the methimazole
      treatment; and again 5.8 +/- 0.8 months later when euthyroidism had been
      established; and in 30 healthy age- and gender-matched controls. Postocclusive
      reactive hyperaemia (PRH) was assessed by a 3-min occlusion of the brachial
      artery. RESULTS: Baseline LDF on the finger pulp and on the volar forearm were
      significantly higher in untreated GD patients compared to treated GD patients and
      controls (p <  0.05 for both). On the finger pulp, the time to maximal LDF during
      PRH was significantly shorter in untreated GD patients compared to controls (p < 
      0.05). On the forearm, the duration of PRH was significantly longer in untreated
      GD patients compared to controls (p <  0.05). Positive correlations of
      triiodothyronine and TSAb with some indices of PRH were established in treated GD
      patients. CONCLUSIONS: Hyperthyroidism induced by GD reversibly affects skin
      microcirculation, presumably by increasing the vasodilator capacity. Potential
      involvement of TSAb might be implicated.

PMID- 25373930
TI  - Characterization and quantification of gamma-oryzanol in grains of 16 Korean rice
      varieties.
AB  - gamma-Oryzanol, a mixture of ferulic acid esters of triterpene alcohols and
      sterols, is a nutritionally important group of rice secondary metabolites. A
      library of 27 gamma-oryzanol was assembled from existing data and used to assist
      identification and quantification of gamma-oryzanol isolated from 16 Korean rice
      varieties (11 white and 5 pigmented). gamma-Oryzanol was analyzed with liquid
      chromatography with diode array detection and electrospray ionization mass
      spectrometry. Nineteen different gamma-oryzanol were observed and identified as
      stigmasterol, campesterol and sitosterol or common and hydroxylated triterpene
      alcohols. In the 16 varieties, the total gamma-oryzanol content averaged 43.8
      mg/100 g (range, 26.7-61.6 mg/100 g), which Josaengheugchal exhibited the highest
      level (61.6 mg/100 g). The Korean rice varieties were classified based on
      qualitative and quantitative gamma-oryzanol data by multivariate statistical
      analysis. Clusters of specialty rice varieties exhibited higher gamma-oryzanol
      levels than those of common rice varieties.

PMID- 25373931
TI  - Treatment with Lingqi capsules suppresses colorectal cancer by inhibiting the
      hepatocyte growth factor/c-Met signal transduction pathway.
AB  - Lingqi capsules (LQCs) are commonly used in Chinese herbal medicine to support
      the immune system and inhibit tumor growth. The capsules are considered to have a
      direct effect on tumor cell proliferation and support tumor cell apoptosis. In
      the present study, the effects of LQC serum on the colorectal cancer cell line,
      LoVo, and on tumors induced by the cell line were investigated in nude mice. LQC
      serum was generated by feeding Wistar rats LQC and isolating the serum from blood
      samples obtained from the rats. The serum was then used to treat LoVo cells for
      24, 48 and 72 h, after which the cell morphology and proliferation were assessed.
      In addition, nude mice were injected with 0.2 ml LoVo cells subcutaneously to
      produce tumors. After 24 h, xenografted nude mice were treated with 5.0, 2.5 or
      1.25 g/kg/day LQC serum by gavage for 21 days and the tumor growth, morphology,
      apoptosis of tumor cells and expression profiles of hepatocyte growth factor
      (HGF) and its receptor, c-Met, were investigated. Compared with the negative
      controls, inhibition of cell growth was clearly visible in the LoVo cells treated
      for 24, 48 and 72 h and this inhibition was enhanced as the exposure time and
      drug concentration increased. The growth of solid tumors induced by the
      transplantation of LoVo cells into nude mice was inhibited to differing degrees.
      Following LQC treatment, the apoptotic rates of the cells were increased, the
      protein and mRNA expression levels of HGF were downregulated and those of c-Met
      were upregulated. These findings suggest that LQC treatment inhibits colorectal
      cancer by downregulating the HGF/c-Met signal transduction pathway.

PMID- 25373932
TI  - Neuromechanical control of the forearm muscles during gripping with sudden
      flexion and extension wrist perturbations.
AB  - The purpose of this study was to investigate how gripping modulates forearm
      muscle co-contraction prior to and during sudden wrist perturbations. Ten males
      performed a sub-maximal gripping task (no grip, 5% and 10% of maximum) while a
      perturbation forced wrist flexion or extension. Wrist joint angles and activity
      from 11 muscles were used to determine forearm co-contraction and muscle
      contributions to wrist joint stiffness. Co-contraction increased in all pairs as
      grip force increased (from no grip to 10% grip), corresponding to a 36% increase
      in overall wrist joint stiffness. Inclusion of individual muscle contributions to
      wrist joint stiffness enhanced the understanding of forearm co-contraction. The
      extensor carpi radialis longus (ECRL) and brevis had the largest stiffness
      contributions (34.5 +/- 1.3% and 20.5 +/- 2.3%, respectively), yet muscle pairs
      including ECRL produced the lowest co-contraction. The muscles contributing most
      to wrist stiffness were consistent across conditions (ECRL for extensors; Flexor
      Digitorum Superficialis for flexors), suggesting enhanced contributions rather
      than muscular redistribution. This work provides investigation of the
      neuromuscular response to wrist perturbations and gripping demands by considering
      both co-contraction and muscle contributions to joint stiffness. Individual
      muscle stiffness contributions can be used to enhance the understanding of
      forearm muscle control during complex tasks.

PMID- 25373934
TI  - Magnetic control of valley and spin degrees of freedom via magnetotransport in n
      type monolayer MoS2.
AB  - We study the quantum magnetotransport properties at low temperature for n-type
      monolayer MoS2 under a perpendicular magnetic field within the linear response
      theory. By using Kubo formula, it is predicted that the valley- and spin-resolved
      Hall conductance obeys the same rule as that for conventional fermions. However,
      the first Hall plateau and the longitudinal charge conductance in low energies
      are fully valley/spin-polarized, which may produce a pure valley/spin current. In
      the low magnetic field limit, importantly, the resistance as a function of field
      is in good agreement with the available experiment data. These interesting
      findings can be tested experimentally and may be useful for valleytronic and
      spintronic applications. 

PMID- 25373933
TI  - The accuracy of renal tumor biopsy: analysis from a national prospective study.
AB  - OBJECTIVE: To assess preoperative renal tumor biopsy (RTB) accuracy. MATERIALS
      AND METHODS: As part of the prospective NEPHRON study, data from 1,237 renal
      tumors were collected, including the use and results of RTB and final histology
      following nephrectomy. During the 6 months period of inclusion, 130 preoperative
      biopsies were performed. We used the kappa coefficient of the McNemar test to
      determine the concordance between the biopsy and the nephrectomy specimen (NS)
      regarding four parameters: malignant/benign status, histological subtype, Fuhrman
      grade and microscopic necrosis. RESULTS: Preoperative biopsies were performed in
      9.7 and 11.4 % of the 667 radical and 570 partial nephrectomies, respectively.
      Tumor biopsy was inconclusive in 7.7 % of the cases. In 117 cases, a comparison
      between RTB and NS was available. Benign tumors accounted for three (2.6 %) and
      five (4.3 %) of the RTB and NS, respectively (kappa = 0.769, good). With seven (6
      %) discordant results in terms of histological subtype characterization between
      RTB and final pathology, RTB accuracy was considered excellent (kappa = 0.882).
      In 33 cases (31.7 %), Fuhrman grade was underestimated at biopsy resulting in an
      intermediate concordance level (kappa = 0.498). Tumor microscopic necrosis was
      identified in 12 RTB (10.4 %) versus 33 NS (28.4 %) (kappa = 0.357, poor).
      CONCLUSIONS: RTB provides good to excellent diagnostic performance for
      discriminating malignancy and tumor histological subtype. However, its
      performance is intermediate or even poor when considering prognostic criteria
      like Fuhrman grade or microscopic necrosis. Thus, this possible inaccuracy should
      be taken into consideration when using RTB for accurate guidance of treatment
      strategy.

PMID- 25373935
TI  - Stool fatty acid soaps, stool consistency and gastrointestinal tolerance in term
      infants fed infant formulas containing high sn-2 palmitate with or without
      oligofructose: a double-blind, randomized clinical trial.
AB  - BACKGROUND: Formula-fed (FF) infants often have harder stools and higher stool
      concentrations of fatty acid soaps compared to breastfed infants. Feeding high sn
      2 palmitate or the prebiotic oligofructose (OF) may soften stools, reduce stool
      soaps, and decrease fecal calcium loss. METHODS: We investigated the effect of
      high sn-2 palmitate alone and in combination with OF on stool palmitate soap,
      total soap and calcium concentrations, stool consistency, gastrointestinal (GI)
      tolerance, anthropometrics, and hydration in FF infants. This double-blind trial
      randomized 165 healthy term infants 25-45 days old to receive Control formula (n
      = 54), formula containing high sn-2 palmitate (sn-2; n = 56), or formula
      containing high sn-2 palmitate plus 3 g/L OF (sn-2+OF; n = 55). A non-randomized
      human milk (HM)-fed group was also included (n = 55). The primary endpoint, stool
      composition, was determined after 28 days of feeding, and was assessed using
      ANOVA accompanied by pairwise comparisons. Stool consistency, GI tolerance and
      hydration were assessed at baseline, day 14 (GI tolerance only) and day 28.
      RESULTS: Infants fed sn-2 had lower stool palmitate soaps compared to Control (P
      = 0.0028); while those fed sn-2+OF had reduced stool palmitate soaps compared to
      both Control and sn-2 (both P < 0.0001). Stool total soaps and calcium were lower
      in the sn-2+OF group than either Control (P < 0.0001) or sn-2 (P < 0.0001). The
      HM-fed group had lower stool palmitate soaps, total soaps and calcium (P < 0.0001
      for each comparison) than all FF groups. The stool consistency score of the sn
      2+OF group was lower than Control and sn-2 (P < 0.0001), but higher than the HM
      fed group (P < 0.0001). GI tolerance was similar and anthropometric z-scores were
      <0.2 SD from the WHO growth standards in all groups, while urinary hydration
      markers were within normal range for all FF infants. CONCLUSIONS: Increasing sn-2
      palmitate in infant formula reduces stool palmitate soaps. A combination of high
      sn-2 palmitate and OF reduces stool palmitate soaps, total soaps and calcium,
      while promoting softer stools. TRIAL REGISTRATION: This study was registered on
      http://www.clinicaltrials.gov: number NCT02031003.

PMID- 25373936
TI  - Relative femoral neck lengthening improves pain and hip function in proximal
      femoral deformities with a high-riding trochanter.
AB  - BACKGROUND: Complex proximal femoral deformities, including an elevated greater
      trochanter, short femoral neck, and aspherical head-neck junction, often result
      in pain and impaired hip function resulting from intra-/extraarticular
      impingement. Relative femoral neck lengthening may address these deformities, but
      mid-term results of this approach have not been widely reported.
      QUESTIONS/PURPOSES: Do patients who have undergone relative femoral neck
      lengthening show (1) less hip pain and greater function; (2) improved
      radiographic parameters; (3) significant complications requiring subsequent
      surgery; and (4) progression of osteoarthrosis (OA) or conversion to total hip
      arthroplasty (THA) at mid-term followup? METHODS: We retrospectively reviewed 40
      patients (41 hips) with isolated relative femoral neck lengthening between 1998
      and 2006 with sequelae of Legg-Calve-Perthes disease (38 hips [93%]), slipped
      capital femoral epiphysis (two hips [5%]), and postseptic arthritis (one hip
      [2%]). During this time, the general indications for this procedure included a
      high-riding greater trochanter with a short femoral neck with abductor weakness
      and symptomatic intra-/extraarticular impingement. Mean patient followup was 8
      years (range, 5-13 years), and complete followup was available in 38 patients (39
      hips [95%]). We evaluated pain and function with the impingement test, limp,
      abductor force, Merle d'Aubigne-Postel score, and range of motion. Radiographic
      parameters included trochanteric height, alpha angle, and progression of OA.
      Subsequent surgeries, complications, and conversion to THA were summarized.
      RESULTS: The proportion of positive anterior impingement tests decreased from 93%
      (38 of 41 hips) preoperatively to 49% (17 of 35 hips) at latest followup (p =
      0.002); the proportion of limp decreased from 76% (31 of 41 hips) to 9% (three of
      35 hips; p < 0.001); the proportion of normal abductor strength increased from
      17% (seven of 41 hips) to 91% (32 of 35 hips; p < 0.001); mean Merle d'Aubigne
      Postel score increased from 14 +/- 1.7 (range, 9-17) to 17 +/- 1.5 (range, 13-18;
      p < 0.001); mean internal rotation increased to 25 degrees  +/- 15 degrees 
      (range, 0 degrees -60 degrees ; p = 0.045), external rotation to 32 degrees  +/-
      14 degrees  (range, 5 degrees -70 degrees ; p = 0.013), and abduction to 37
      degrees  +/- 13 degrees  (range, 10 degrees -50 degrees ; p = 0.004). Eighty
      percent of hips (33 of 41 hips) showed normal trochanteric height; alpha angle
      improved to 42 degrees  +/- 10 degrees  (range, 27 degrees -90 degrees ). Two
      hips (5%) had subsequent surgeries as a result of lack of containment; four of 41
      hips (10%) had complications resulting in reoperation. Fourteen of 35 hips (40%)
      showed progression of OA; four of 40 hips (10%) converted to THA. CONCLUSIONS:
      Relative femoral neck lengthening in hips with combined intra- and extraarticular
      impingement results in reduced pain, improved function, and improved radiographic
      parameters of the proximal femur. Although lack of long-term complications is
      gratifying, progression of OA was not prevented and remains an area for future
      research.

PMID- 25373937
TI  - Letter to the editor: how does ulnar shortening osteotomy influence morphologic
      changes in the triangular fibrocartilage complex?

PMID- 25373939
TI  - Interaural-phase discrimination in notched noise.
AB  - Discrimination thresholds for the interaural-phase difference (IPD) of a 500-Hz
      sinusoid were measured in the presence of a diotic notched-noise masker as a
      function of notch width. The reference sinusoid had zero IPD. The level was set
      to 3 dB above the individual masked threshold for the diotic sinusoid at the
      respective notch width. Just-noticeable IPDs increased from about 20 degrees  for
      notch widths up to 100 Hz to 100 degrees  at the largest notch width of 800 Hz.
      Model simulations show that the data are consistent with the equalization
      cancellation theory, if effectively wider binaural filters are assumed. 

PMID- 25373938
TI  - Prevalence of thyroid dysfunction with adequate and excessive iodine intake in
      Hebei Province, People's Republic of China.
AB  - OBJECTIVE: To explore (i) the prevalence of thyroid dysfunction in populations
      with adequate and excessive iodine intakes and (ii) the effect of iodine exposure
      on the prevalence of thyroid dysfunction. DESIGN: Cross-sectional study was
      conducted in Hebei in 2010. The population was classified as having adequate or
      excessive iodine intake according to the iodine concentration in drinking water.
      Demographic information was collected by questionnaire. Levels of serum thyroid
      hormones, thyroid autoantibodies and iodine in drinking water and urine were
      measured. SETTING: Villages with adequate or excessive drinking water iodine in
      Hebei Province, People's Republic of China. SUBJECTS: A total of 854 men and
      women aged 20-50 years who had lived in the surveyed areas for over 5 years,
      including 348 from the adequate iodine area (AIA) and 506 from the excessive
      iodine area (EIA). RESULTS: Median urinary iodine concentration was 185 MUg/l in
      AIA and 1152 MUg/l in EIA. The prevalence of thyroid dysfunction in AIA was
      10.3%, which included 1.1% with hypothyroidism and 8.1% with subclinical
      hypothyroidism; and 20.6% in EIA, which included 3.6% with hypothyroidism and
      13.6% with subclinical hypothyroidism. The positive rates of thyroglobulin
      antibody were 16.1% in AIA and 11.9% in EIA; the positive rates of
      thyroperoxidase antibody were 20.7% in AIA and 16.4% in EIA. CONCLUSIONS:
      Excessive iodine intake may lead to increased prevalence of biochemical thyroid
      dysfunction, especially biochemical hypothyroidism. This is not related to an
      increase in prevalence of thyroid antibodies. Women are more susceptible to
      iodine excess.

PMID- 25373940
TI  - Scattering by an array of perforated cylinders with a porous core.
AB  - In this work multiple scattering by an array of perforated cylindrical shells
      with a porous core has been investigated. A semi-analytical model to predict
      scattering from such cylindrical units is presented in the context of the
      multiple scattering theory (MST), and validated against laboratory experiments.
      The suggested semi-analytical multiple scattering model uses an impedance
      expression to include the perforated shell in the scattering coefficients, which
      is a compact way to describe a composite scatterer in MST. Calculation results of
      a small array are shown to be in excellent agreement with measured data.
      Predictions and data show that perforated cylinders with empty cavities exhibit a
      strong and narrow insertion loss peak at resonance, though simultaneously suffer
      from amplification below resonance. By adding porous material in the core of the
      scatterer adverse effects below the resonance peak were suppressed. In addition,
      it was found that the reduction peak broadens, though at a cost of a reduced peak
      amplitude. Finally, it has been shown that adding porous material in a perforated
      shell will introduce partial absorption of the incoming field, which can be
      optimized by adjusting the perforation ratio of the shell. 

PMID- 25373941
TI  - One-dimensional single-sided acoustic focusing in a Goupillaud layered model.
AB  - Using the single-sided reflection response of an unknown layered medium, one
      dimensional single-sided acoustic focusing is a process that constructs a
      normally incident plane waveform such that the sound field collapses to a point
      inside this medium at a specified time. A recursive method for finding the
      incident waveform of the discrete single-sided focusing in the Goupillaud layered
      model is presented. The method is formulated using the standard Z-transform and
      provides an intuitive way to understand how single-sided focusing works in an
      unknown medium. Two numerical scattering experiments, with different layered
      structures, are simulated to verify the proposed method. In addition, the
      responses to virtual sources in the examples are reconstructed. 

PMID- 25373942
TI  - Mixing of collinear plane wave pulses in elastic solids with quadratic
      nonlinearity.
AB  - This paper derives a set of necessary and sufficient conditions for generating
      resonant waves by two propagating time-harmonic plane waves. It is shown that in
      collinear mixing, a resonant wave can be generated either by a pair of
      longitudinal waves, in which case the resonant mixing wave is also a longitudinal
      wave, or by a pair of longitudinal and transverse waves, in which case the
      resonant wave is a transverse wave. In addition, the paper obtains closed-form
      analytical solutions to the resonant waves generated by two collinearly
      propagating sinusoidal pulses. The results show that amplitude of the resonant
      pulse is proportional to the mixing zone size, which is determined by the spatial
      lengths of the input pulses. Finally, numerical simulations based on the finite
      element method and experimental measurements using one-way mixing are conducted.
      It is shown that both numerical and experimental results agree well with the
      analytical solutions. 

PMID- 25373943
TI  - Acoustic radiation force and torque on an absorbing compressible particle in an
      inviscid fluid.
AB  - Exact formulas of the acoustic radiation force and torque exerted by an arbitrary
      time-harmonic wave on an absorbing compressible particle that is suspended in an
      inviscid fluid are presented. It is considered that the particle diameter is much
      smaller than the incident wavelength, i.e., the so-called Rayleigh scattering
      limit. Moreover, the particle absorption assumed here is due to the attenuation
      of compressional waves only. Shear waves inside and outside the particle are
      neglected, since the inner and outer viscous boundary layer of the particle are
      supposed to be much smaller than the particle radius. The obtained radiation
      force formulas are used to establish the trapping conditions of a particle by a
      single-beam acoustical tweezer based on a spherically focused ultrasound
      transducer. In this case, it is shown that the particle absorption has a pivotal
      role in single-beam trapping at the transducer focal region. Furthermore, it is
      found that only the first-order Bessel vortex beam can generate the radiation
      torque on a small particle. In addition, numerical evaluation of the radiation
      force and torque exerted on a benzene and an olive oil droplet suspended in water
      are presented and discussed. 

PMID- 25373944
TI  - Spatial-temporal coherence of acoustic signals propagating in a refractive,
      turbulent atmosphere.
AB  - Propagation of acoustic signals above an impedance ground in a refractive,
      turbulent atmosphere with spatial-temporal fluctuations in temperature and wind
      velocity is considered. Starting from a parabolic equation, and using the Markov
      approximation and a locally frozen turbulence hypothesis, closed-form equations
      for the spatial-temporal statistical moments of arbitrary order of the sound
      pressure field are derived. The general theory provides a basis for analysis of
      many statistical characteristics of broadband and narrowband acoustic signals for
      different geometries of propagation: line-of-sight propagation, multipath
      propagation in a refractive atmosphere above an impedance ground, and sound
      scattering into a refractive shadow zone. As an example of application of this
      theory, the spatial-temporal coherence of narrowband acoustic signals for line-of
      sight propagation is calculated and analyzed. The coherence time of acoustic
      signals is studied numerically for meteorological conditions ranging from cloudy
      to sunny conditions, and with light, moderate, and strong wind. The results
      obtained are compared with available experimental data. 

PMID- 25373945
TI  - Optimizing thermoacoustic regenerators for maximum amplification of acoustic
      power.
AB  - Identifying optimum design parameters and operating conditions of thermoacoustic
      engines or refrigerators is crucial for the further development of such devices.
      This publication proposes an optimization criterion for the stack of a
      thermoacoustic device with the objective of maximizing the amplification of
      acoustic energy by the stack. For this purpose, the stack is described as an
      acoustic multi-port, represented mathematically by its scattering matrix. It is
      shown how the scattering matrix may be deduced from the standard thermo-acoustic
      governing equations. Then an acoustic power balance is deduced from the
      scattering matrix. The spectral norm and the eigenvectors of the scattering
      matrix identify optimal acoustic states. Stack design operating parameters and
      frequencies with maximum amplification of acoustic power are identified for
      various stack configurations. The corresponding acoustic states are interpreted
      physically. 

PMID- 25373946
TI  - Stability analysis and design of time-domain acoustic impedance boundary
      conditions for lined duct with mean flow.
AB  - This work develops the so-called compensated impedance boundary conditions that
      enable stable time domain simulations of sound propagation in a lined duct with
      uniform mean flow, which has important practical interest for noise emission by
      aero-engines. The proposed method is developed analytically from an unusual
      perspective of control that shows impedance boundary conditions act as closed
      loop feedbacks to an overall duct acoustic system. It turns out that those
      numerical instabilities of time domain simulations are caused by deficient phase
      margins of the corresponding control-oriented model. A particular instability of
      very low frequencies in the presence of steady uniform background mean flow, in
      addition to the well known high frequency numerical instabilities at the grid
      size, can be identified using this analysis approach. Stable time domain
      impedance boundary conditions can be formulated by including appropriate
      phaselead compensators to achieve desired phase margins. The compensated
      impedance boundary conditions can be simply designed with no empirical parameter,
      straightforwardly integrated with ordinary linear acoustic models, and
      efficiently calculated with no need of resolving sheared boundary layers. The
      proposed boundary conditions are validated by comparing against asymptotic
      solutions of spinning modal sound propagation in a duct with a hard-soft
      interface and reasonable agreement is achieved. 

PMID- 25373947
TI  - Evidence of three-dimensional acoustic propagation in the Catoche Tongue.
AB  - This paper presents observations of two classes of acoustic arrivals recorded on
      a sparsely populated vertical line array (VLA) moored in the center of the
      Catoche Tongue, a major reentrant in the Campeche Bank in the southeastern Gulf
      of Mexico. The acoustic signals were generated by signals underwater sound (SUS)
      located 50-80 km from the VLA. The first class of arrivals was identified as
      resulting from a direct (non-horizontally refracted) path. Then following a
      quiescent period, a second, more diffuse class of arrivals is observed and is
      believed to be the result of horizontal refraction from the margin of the Tongue.
      A spectral analysis of the measured data revealed that both classes of arrivals
      were characterized by the source spectrum associated with SUS. Additionally, the
      difference in time between the onset of the first and second class of arrivals
      observed as a function of range from the VLA is consistent with the relative
      difference in the length of the direct and refracted paths. The observations are
      further supported by a three-dimensional (3D) acoustic propagation computation
      that reproduces many of the features of the measured data and provides additional
      insight into the details of the 3D propagation. 

PMID- 25373948
TI  - The significance of parameter uncertainties for the prediction of offshore pile
      driving noise.
AB  - Due to the construction of offshore wind farms and its potential effect on marine
      wildlife, the numerical prediction of pile driving noise over long ranges has
      recently gained importance. In this contribution, a coupled finite
      element/wavenumber integration model for noise prediction is presented and
      validated by measurements. The ocean environment, especially the sea bottom, can
      only be characterized with limited accuracy in terms of input parameters for the
      numerical model at hand. Therefore the effect of these parameter uncertainties on
      the prediction of sound pressure levels (SPLs) in the water column is
      investigated by a probabilistic approach. In fact, a variation of the bottom
      material parameters by means of Monte-Carlo simulations shows significant effects
      on the predicted SPLs. A sensitivity analysis of the model with respect to the
      single quantities is performed, as well as a global variation. Based on the
      latter, the probability distribution of the SPLs at an exemplary receiver
      position is evaluated and compared to measurements. The aim of this procedure is
      to develop a model to reliably predict an interval for the SPLs, by quantifying
      the degree of uncertainty of the SPLs with the MC simulations. 

PMID- 25373949
TI  - Dipole transducer enhancement from a passive resonator.
AB  - A passive resonator model for enhancing the low frequency performance of dipole
      transducers is presented using a spherical wave function model. It is shown that
      because the near field response of a dipole has the same on-axis low frequency
      dependence as an equivalent monopole, it can effectively excite a nearby monopole
      passive resonator and do this with enough strength to significantly modify the
      response of the system. Sample results are presented to demonstrate the
      performance enhancement and to illustrate the conversion of the dipole beam
      pattern to a nearly omni-directional beam pattern. 

PMID- 25373950
TI  - Analysis of shear-wave attenuation in unconsolidated sands and glass beads.
AB  - Chotiros and Isakson [J. Acoust. Soc. Am. 135, 3264-3279 (2014)] contend that the
      physics-based grain-shearing (GS) theories of wave propagation in granular
      materials are not consistent with one particular shear-attenuation data set for
      water-saturated angular sand that has appeared in the literature. This provides
      them with the rationale for developing their own model, an extension of the
      empirical Biot-Stoll model, which they designate the Extended Biot (EB) model. In
      this article, the EB model and the grain-shearing theories are briefly reviewed,
      and it is demonstrated that, in fact, the original GS theory accurately matches
      the frequency-dependent trends of all the shear attenuation data sets that are
      currently available, including those for saturated angular sands after random
      fluctuations are suppressed by averaging over several realizations of the medium.
      It is also pointed out that Chotiros and Isakson's treatment of the available
      shear-attenuation data is highly selective, and that the format in which they
      present the selected data makes their comparisons with theoretical models
      difficult to interpret. Thus, their attempts at validating the EB model and their
      conclusions concerning alternative theories should be treated with caution. 

PMID- 25373951
TI  - Energy balance during underwater implosion of ductile metallic cylinders.
AB  - Energy-based metrics are developed and applied to a numerical test case of
      implosion of an underwater pressure vessel. The energy metrics provide estimates
      of the initial energy in the system (potential energy), the energy released into
      the fluid as a pressure pulse, the energy absorbed by the imploding structure,
      and the energy absorbed by air trapped within the imploding structure. The
      primary test case considered is the implosion of an aluminum cylinder [diameter:
      2.54 cm (1 in.), length: 27.46 cm (10.81 in.)] that collapses flat in a mode-2
      shape with minimal fracture. The test case indicates that the structure absorbs
      the majority (92%) of the initial energy in the system. Consequently, the energy
      emitted as a pressure pulse into the fluid is a small fraction, approximately 5%,
      of the initial energy. The energy absorbed by the structure and the energy
      emitted into the fluid are calculated for additional simulations of underwater
      pressure vessel implosions. For all cases investigated, there is minimal fracture
      in the collapse, the structure absorbs more than 80% of the initial energy of the
      system, and the released pressure pulse carries away less than 6% of the initial
      energy. 

PMID- 25373952
TI  - On the spatial properties of ambient noise in the Tonga Trench, including effects
      of bathymetric shadowing.
AB  - In September 2012, the free-falling, deep-diving instrument platform Deep Sound
      III descended to the bottom of the Tonga Trench, where it resided at a depth of
      8515 m for almost 3 h, recording ambient noise data on four hydrophones arranged
      in a vertical L-shaped configuration. The time series from each of the
      hydrophones yielded the power spectrum of the noise over the frequency band 3 Hz
      to 30 kHz. The spatial coherence functions, along with the corresponding cross
      correlation functions, were recovered from all available hydrophone pairs in the
      vertical and the horizontal. The vertical coherence and cross-correlation data
      closely follow the predictions of a simple theory of sea-surface noise in a semi
      infinite ocean, suggesting that the seabed in the Tonga Trench is a very poor
      acoustic reflector, which is consistent with the fact that the sediment at the
      bottom of the trench consists of very-fine-grained material having an acoustic
      impedance similar to that of seawater. The horizontal coherence and cross
      correlation data are a little more complicated, showing evidence of (a)
      bathymetric shadowing of the noise by the walls of the trench and (b) highly
      directional acoustic arrivals from the research vessel supporting the experiment.

PMID- 25373953
TI  - Signal processing and tracking of arrivals in ocean acoustic tomography.
AB  - The signal processing for ocean acoustic tomography experiments has been improved
      to account for the scattering of the individual arrivals. The scattering reduces
      signal coherence over time, bandwidth, and space. In the typical experiment,
      scattering is caused by the random internal-wave field and results in pulse
      spreading (over arrival-time and arrival-angle) and wander. The estimator
      correlator is an effective procedure that improves the signal-to-noise ratio of
      travel-time estimates and also provides an estimate of signal coherence. The
      estimator-correlator smoothes the arrival pulse at the expense of resolution.
      After an arrival pulse has been measured, it must be associated with a model
      arrival, typically a ray arrival. For experiments with thousands of
      transmissions, this is a tedious task that is error-prone when done manually. An
      error metric that accounts for peak amplitude as well as travel-time and arrival
      angle can be defined. The Viterbi algorithm can then be adapted to the task of
      automated peak tracking. Repeatable, consistent results are produced that are
      superior to a manual tracking procedure. The tracking can be adjusted by tuning
      the error metric in logical, quantifiable manner. 

PMID- 25373954
TI  - A theoretical model of linearly filtered reverberation for pulsed active sonar in
      shallow water.
AB  - This paper presents a statistical model useful for characterizing pulsed active
      sonar reverberation in shallow water. The model is based on the fundamental
      assumption that reverberation consists of echoes from point scatterers having
      random positions, strengths, and Doppler dilations. Receive array beam patterns,
      simple propagation losses, and planar bistatic geometry are included. The
      probability distribution of uniformly dense scatterers as a function of echo
      delay and bearing is explicitly related to the change in the area from which
      scatterer echoes contribute to the reverberation, and is presented in closed
      form. The cross Q-function of the transmitted waveform and the linear filter
      applied to the received signal arises naturally from the development. This
      function, along with environmental spreading, determines the shape of the
      reverberation along the Doppler axis. The assumptions and simplifications under
      which the reverberation decouples into independent spatial (delay and bearing)
      and Doppler terms are presented. 

PMID- 25373955
TI  - Investigating the thermally induced acoustoelastic effect in isotropic media with
      Lamb waves.
AB  - Elastic wave velocities in metallic structures are affected by variations in
      environmental conditions such as changing temperature. This paper extends the
      theory of acoustoelasticity by allowing thermally induced strains in
      unconstrained isotropic media, and it experimentally examines the velocity
      variation of Lamb waves in aluminum plates (AL-6061) due to isothermal
      temperature deviations. This paper presents both thermally induced acoustoelastic
      constants and thermally varying effective Young's modulus and Poisson's ratio
      which include the third order elastic material constants. The experimental
      thermal sensitivity of the phase velocity (?v(P)/?theta) for both the symmetric
      and antisymmetric modes are bounded by two theories, the acoustoelastic Lamb wave
      theory with thermo-acoustoelastic tensors and the thermoelastic Lamb wave theory
      using an effective thermo-acoustoelastic moduli. This paper shows the theoretical
      thermally induced acoustoelastic Lamb wave thermal sensitivity (?v(P)/?theta) is
      an upper bound approximation of the experimental thermal changes, but the
      acoustoelastic Lamb wave theory is not valid for predicting the antisymmetric
      (A0) phase velocity at low frequency-thickness values, <1.55 MHz mm for various
      temperatures.

PMID- 25373956
TI  - A transmission-line model of back-cavity dynamics for in-plane pressure
      differential microphones.
AB  - Pressure-differential microphones inspired by the hearing mechanism of a special
      parasitoid fly have been described previously. The designs employ a beam
      structure that rotates about two pivots over an enclosed back volume. The back
      volume is only partially enclosed due to open slits around the perimeter of the
      beam. The open slits enable incoming sound waves to affect the pressure profile
      in the microphone's back volume. The goal of this work is to study the net moment
      applied to pressure-differential microphones by an incoming sound wave, which in
      turn requires modeling the acoustic pressure distribution within the back volume.
      A lumped-element distributed transmission-line model of the back volume is
      introduced for this purpose. It is discovered that the net applied moment follows
      a low-pass filter behavior such that, at frequencies below a corner frequency
      depending on geometrical parameters of the design, the applied moment is
      unaffected by the open slits. This is in contrast to the high-pass filter
      behavior introduced by barometric pressure vents in conventional omnidirectional
      microphones. The model accurately predicts observed curvature in the frequency
      response of a prototype pressure-differential microphone 2 mm * 1 mm * 0.5 mm in
      size and employing piezoelectric readout. 

PMID- 25373957
TI  - Electroacoustic analysis, design, and implementation of a small balanced armature
      speaker.
AB  - This paper presents a new design and implementation of a balanced armature
      speaker (BAS), which is composed of permanent magnetic circuits, a moving
      armature, and a coil. The armature rocks about a pivot with the coil at one end
      and the permanent magnet on another. A magnetic circuit analysis is conducted for
      the designed BAS to formulate the force factor, which is required for modeling
      the coupling between the electrical and mechanical systems. In addition, an
      electromechanoacoustical analogous circuit is established for the BAS, which
      bears the same structure as the moving coil loudspeaker, except that the force
      factor is different. A hybrid model, which combines the lumped parameter model in
      the electrical and acoustical domains with a finite element model in the
      mechanical domain, is developed to model the high-frequency response because of
      the high-order modes of the membrane, the drive rod, and the armature. The
      electroacoustic analysis is experimentally verified. The results indicate that
      the sound pressure response that is simulated using the hybrid model is in
      superior agreement with the measured response to that simulated using the lumped
      parameter model. 

PMID- 25373958
TI  - Nondestructive measurement of neutral temperature in continuous welded rails by
      nonlinear ultrasonic guided waves.
AB  - Modern rail construction uses continuous-welded rail (CWR). The presence of very
      few joints leads to an increasing concern due to the large longitudinal loads
      caused by restrained thermal expansion and contraction, following seasonal
      temperature variations. The knowledge of the current state of thermal stress in
      the rail or, equivalently, the rail neutral temperature (corresponding to zero
      net longitudinal force) is a key need within the railroad transportation
      community in order to properly schedule slow-order mandates and prevent
      derailments. This paper presents a nondestructive diagnostic system for
      measurement of the neutral temperature in CWR based on nonlinear ultrasonic
      guided waves. The theoretical part of the study involved the development of a
      constitutive model in order to explain the origin of nonlinear effects arising in
      complex waveguides under constrained thermal expansion. A numerical framework has
      been implemented to predict internal resonance conditions of nonlinear waves in
      complex waveguides. This theoretical/numerical phase has led to the development
      of an experimental prototype (Rail-NT) that was tested both in the laboratory and
      in the field. The results of these experimental tests are also summarized. 

PMID- 25373959
TI  - Minimizing the acoustic power radiated by a fluid-loaded curved panel excited by
      turbulent boundary layer flow.
AB  - In order to address noise control problems in the design stage, structural
      acoustic optimization procedures can be used to find the optimal design for
      reduced noise or vibration. However, most structural-acoustic optimization
      procedures are not general enough to include both heavy fluid loading and complex
      forcing functions. Additionally, it can be difficult to determine and assess
      trade-offs between weight and sound radiation. A structural-acoustic optimization
      approach is presented for minimizing the radiated power of structures with heavy
      fluid loading excited by complex forcing functions. The procedure is demonstrated
      on a curved underwater panel excited by a point drive and by turbulent boundary
      layer flow. To facilitate more efficient analysis, an uncorrelated pressure
      assumption is made for the turbulent boundary layer forcing function. The
      thicknesses of groups of elements were used as the design variables with an
      adaptive covariance matrix evolutionary strategy as the search algorithm. The
      objective function was a weighted sum of total sound power and panel mass and the
      Pareto front was computed to show the optimum trade-off between the two
      objectives. The optimal designs are presented which illustrate the best methods
      for reducing radiated sound and mass simultaneously. 

PMID- 25373960
TI  - Structural-change localization and monitoring through a perturbation-based
      inverse problem.
AB  - Structural-change detection and characterization, or structural-health
      monitoring, is generally based on modal analysis, for detection, localization,
      and quantification of changes in structure. Classical methods combine both
      variations in frequencies and mode shapes, which require accurate and spatially
      distributed measurements. In this study, the detection and localization of a
      local perturbation are assessed by analysis of frequency changes (in the
      fundamental mode and overtones) that are combined with a perturbation-based
      linear inverse method and a deconvolution process. This perturbation method is
      applied first to a bending beam with the change considered as a local
      perturbation of the Young's modulus, using a one-dimensional finite-element model
      for modal analysis. Localization is successful, even for extended and multiple
      changes. In a second step, the method is numerically tested under ambient-noise
      vibration from the beam support with local changes that are shifted step by step
      along the beam. The frequency values are revealed using the random decrement
      technique that is applied to the time-evolving vibrations recorded by one sensor
      at the free extremity of the beam. Finally, the inversion method is
      experimentally demonstrated at the laboratory scale with data recorded at the
      free end of a Plexiglas beam attached to a metallic support. 

PMID- 25373961
TI  - Experimental active structural acoustic control of simply supported plates using
      a weighted sum of spatial gradients.
AB  - A limitation currently facing active structural acoustic control (ASAC)
      researchers is that an ideal minimization quantity for use in the control
      algorithms has not been developed. A novel parameter termed the "weighted sum of
      spatial gradients" (WSSG) was recently developed for use in ASAC and shown to
      effectively attenuate acoustic radiation from a vibrating flat simply supported
      plate in computer simulations. This paper extends this research from computer
      simulations and provides experimental test results. The results presented show
      that WSSG is a viable control quantity and provides better results than the
      volume velocity approach. The paper also investigates several of the challenges
      presented by the use of WSSG. These include determining a method to measure WSSG
      experimentally, an analysis of the influence of noise on WSSG control results and
      complications presented when degenerate modes exist. Results are shown and
      discussed for several experimental configurations. 

PMID- 25373962
TI  - Audio-visual interaction and perceptual assessment of water features used over
      road traffic noise.
AB  - This paper examines the audio-visual interaction and perception of water features
      used over road traffic noise, including their semantic aural properties, as well
      as their categorization and evocation properties. The research focused on a wide
      range of small to medium sized water features that can be used in gardens and
      parks to promote peacefulness and relaxation. Paired comparisons highlighted the
      inter-dependence between uni-modal (audio-only or visual-only) and bi-modal
      (audio-visual) perception, indicating that equal attention should be given to the
      design of both stimuli. In general, natural looking features tended to increase
      preference scores (compared to audio-only paired comparison scores), while
      manmade looking features decreased them. Semantic descriptors showed significant
      correlations with preferences and were found to be more reliable design criteria
      than physical parameters. A principal component analysis identified three
      components within the nine semantic attributes tested: "emotional assessment,"
      "sound quality," and "envelopment and temporal variation." The first two showed
      significant correlations with audio-only preferences, "emotional assessment"
      being the most important predictor of preferences, and its attributes
      naturalness, relaxation, and freshness also being significantly correlated with
      preferences. Categorization results indicated that natural stream sounds are
      easily identifiable (unlike waterfalls and fountains), while evocation results
      showed no unique relationship with preferences. 

PMID- 25373963
TI  - Relative variance of the mean-squared pressure in multimode media: rehabilitating
      former approaches.
AB  - The commonly accepted model for the relative variance of transmission functions
      in room acoustics, derived by Weaver, aims at including the effects of
      correlation between eigenfrequencies. This model is based on an analytical
      expression of the relative variance derived by means of an approximated
      correlation function. The relevance of the approximation used for modeling such
      correlation is questioned here. Weaver's model was motivated by the fact that
      earlier models derived by Davy and Lyon assumed independent eigenfrequencies and
      led to an overestimation with respect to relative variances found in practice. It
      is shown here that this overestimation is due to an inadequate truncation of the
      modal expansion, and to an improper choice of the frequency range over which
      ensemble averages of the eigenfrequencies is defined. An alternative definition
      is proposed, settling the inconsistency; predicted relative variances are found
      to be in good agreement with experimental data. These results rehabilitate former
      approaches that were based on independence assumptions between eigenfrequencies.
      Some former studies showed that simpler correlation models could be used to
      predict the statistics of some field-related physical quantity at low modal
      overlap. The present work confirms that this is also the case when dealing with
      transmission functions. 

PMID- 25373964
TI  - Elicitation of attributes for the evaluation of audio-on-audio interference.
AB  - An experiment to determine the perceptual attributes of the experience of
      listening to a target audio program in the presence of an audio interferer was
      performed. The first stage was a free elicitation task in which a total of 572
      phrases were produced. In the second stage, a consensus vocabulary procedure was
      used to reduce these phrases into a comprehensive set of attributes. Groups of
      experienced and inexperienced listeners determined nine and eight attributes,
      respectively. These attribute sets were combined by the listeners to produce a
      final set of 12 attributes: masking, calming, distraction, separation, confusion,
      annoyance, environment, chaotic, balance and blend, imagery, response to stimuli
      over time, and short-term response to stimuli. In the third stage, a simplified
      ranking procedure was used to select only the most useful and relevant
      attributes. Four attributes were selected: distraction, annoyance, balance and
      blend, and confusion. Ratings using these attributes were collected in the fourth
      stage, and a principal component analysis performed. This suggested two
      dimensions underlying the perception of an audio-on-audio interference situation:
      The first dimension was labeled "distraction" and accounted for 89% of the
      variance; the second dimension, accounting for 10% of the variance, was labeled
      "balance and blend." 

PMID- 25373965
TI  - Listening effort and speech intelligibility in listening situations affected by
      noise and reverberation.
AB  - This study compared the combined effect of noise and reverberation on listening
      effort and speech intelligibility to predictions of the speech transmission index
      (STI). Listening effort was measured in normal-hearing subjects using a scaling
      procedure. Speech intelligibility scores were measured in the same subjects and
      conditions: (a) Speech-shaped noise as the only interfering factor, (b) + (c)
      fixed signal-to-noise ratios (SNRs) of 0 or 7 dB and reverberation as detrimental
      factors, and (d) reverberation as the only detrimental factor. In each condition,
      SNR and reverberation were combined to produce STI values of 0.17, 0.30, 0.43,
      0.57, and 0.70, respectively. Listening effort always decreased with increasing
      STI, thus enabling a rough prediction, but a significant bias was observed
      indicating that listening effort was lower in reverberation only than in noise
      only at the same STI for one type of impulse responses. Accordingly, speech
      intelligibility increased with increasing STI and was significantly better in
      reverberation only than in noise only at the same STI. Further analyses showed
      that the broadband reverberation time is not always a good estimate of speech
      degradation in reverberation and that different speech materials may differ in
      their robustness toward detrimental effects of reverberation. 

PMID- 25373966
TI  - The focal index as a singular metric for beamforming effectiveness.
AB  - Hearing-impaired individuals frequently cite intelligibility problems in multi
      talker environments. Microphone arrays performing time-delay beamforming address
      conditions of poor signal-to-noise ratio by spatially filtering incoming sound.
      Existing beam pattern metrics including peak side lobe level, integrated side
      lobe level, beamwidth, and planar directivity index fail to quantitatively
      capture all elements essential for improving speech intelligibility in multi
      talker situations. The focal index (FI) was developed to address these
      deficiencies. Simulations were performed to exemplify the robust nature of the FI
      and to demonstrate the utility of this metric for driving array parameter
      selection. Beam patterns were generated and the metrics were calculated and
      evaluated against the strict unidirectional requirements for the array. Array
      performance was assessed by human subjects in a speech recognition task that
      incorporated competing speech from multiple locations. Simulations of array
      output were presented under conditions differing in array sparsity. The resulting
      human subject data were used to demonstrate the linear relationship (R(2) >
      0.975) between speech-intelligibility-weighted FI (SII-FI) and the signal-to
      noise ratio thresholds for 20% and 80% correct responses. Data indicate that the
      FI and SII-FI are robust singular metrics for determining the effectiveness of
      the array.

PMID- 25373967
TI  - Sequential filtering for dispersion tracking and sediment sound speed inversion.
AB  - Dispersion curves in ocean environments are accurately estimated from received
      signals through the extraction of instantaneous modal frequencies and
      corresponding arrival times for long-range propagation. The ultimate goal is to
      estimate sediment sound speed using the extracted dispersion pattern. The
      approach extends work previously conducted in dispersion tracking with sequential
      filtering, improving on the latter technique. The sequential state-space method
      that is developed for the extraction of time-frequency information from specific
      time instances relies on a representation of those as a sum of elemental pulses,
      resulting from analysis of the received field. The method is tested on synthetic
      noisy data with different noise levels. After dispersion probability density
      functions are estimated via a particle filter, they are subsequently employed for
      sound speed inversion. Correct mode identification is a challenge impacting
      inversion; this is demonstrated through two examples and a way to remedy the
      problem is discussed. 

PMID- 25373968
TI  - Time-domain delay-and-sum beamforming for time-reversal detection of intermittent
      acoustic sources in flows.
AB  - This study focuses on the identification of intermittent aeroacoustic sources in
      flows by using the time-domain beamforming technique. It is first shown that this
      technique can be seen as a time-reversal (TR) technique, working with approximate
      Green functions in the case of a shear flow. Some numerical experiments
      investigate the case of an array measurement of a generic acoustic pulse emitted
      in a wind-tunnel flow, with a realistic multi-arm spiral array. The results of
      the time-domain beamforming successfully match those given by a numerical TR
      technique over a wide range of flow speeds (reaching the transonic regime). It is
      shown how the results should be analyzed in a focusing plane parallel to the
      microphone array in order to estimate the location and emission time of the pulse
      source. An experimental application dealing with the aeroacoustic radiation of a
      bluff body in a wind-tunnel flow is also considered, and shows that some
      intermittent events can be clearly identified in the noise radiation. Time-domain
      beamforming is then an efficient tool for analyzing intermittent acoustic sources
      in flows, and is a computationally cheaper alternative to the numerical TR
      technique, which should be used for complex configurations where the Green
      function is not available. 

PMID- 25373969
TI  - Scaling of plane-wave functions in statistically optimized near-field acoustic
      holography.
AB  - Statistically Optimized Near-field Acoustic Holography (SONAH) is a Patch
      Holography method, meaning that it can be applied in cases where the measurement
      area covers only part of the source surface. The method performs projections
      directly in the spatial domain, avoiding the use of spatial discrete Fourier
      transforms and the associated errors. First, an inverse problem is solved using
      regularization. For each calculation point a multiplication must then be
      performed with two transfer vectors--one to get the sound pressure and the other
      to get the particle velocity. Considering SONAH based on sound pressure
      measurements, existing derivations consider only pressure reconstruction when
      setting up the inverse problem, so the evanescent wave amplification associated
      with the calculation of particle velocity is not taken into account in the
      regularized solution of the inverse problem. The present paper introduces a
      scaling of the applied plane wave functions that takes the amplification into
      account, and it is shown that the previously published virtual source-plane
      retraction has almost the same effect. The effectiveness of the different
      solutions is verified through a set of simulated measurements.

PMID- 25373970
TI  - Otoacoustic-emission-based medial-olivocochlear reflex assays for humans.
AB  - Otoacoustic emission (OAE) tests of the medial-olivocochlear reflex (MOCR) in
      humans were assessed for viability as clinical assays. Two reflection-source OAEs
      [TEOAEs: transient-evoked otoacoustic emissions evoked by a 47 dB sound pressure
      level (SPL) chirp; and discrete-tone SFOAEs: stimulus-frequency otoacoustic
      emissions evoked by 40 dB SPL tones, and assessed with a 60 dB SPL suppressor]
      were compared in 27 normal-hearing adults. The MOCR elicitor was a 60 dB SPL
      contralateral broadband noise. An estimate of MOCR strength, MOCR%, was defined
      as the vector difference between OAEs measured with and without the elicitor,
      normalized by OAE magnitude (without elicitor). An MOCR was reliably detected in
      most ears. Within subjects, MOCR strength was correlated across frequency bands
      and across OAE type. The ratio of across-subject variability to within-subject
      variability ranged from 2 to 15, with wideband TEOAEs and averaged SFOAEs giving
      the highest ratios. MOCR strength in individual ears was reliably classified into
      low, normal, and high groups. SFOAEs using 1.5 to 2 kHz tones and TEOAEs in the
      0.5 to 2.5 kHz band gave the best statistical results. TEOAEs had more clinical
      advantages. Both assays could be made faster for clinical applications, such as
      screening for individual susceptibility to acoustic trauma in a hearing
      conservation program. 

PMID- 25373971
TI  - Relationship among the physiologic channel interactions, spectral-ripple
      discrimination, and vowel identification in cochlear implant users.
AB  - The hypothesis of this study was that broader patterns of physiological channel
      interactions in the local region of the cochlea are associated with poorer
      spectral resolution in the same region. Electrically evoked compound action
      potentials (ECAPs) were measured for three to six probe electrodes per subject to
      examine the channel interactions in different regions across the electrode array.
      To evaluate spectral resolution at a confined location within the cochlea,
      spectral-ripple discrimination (SRD) was measured using narrowband ripple stimuli
      with the bandwidth spanning five electrodes: Two electrodes apical and basal to
      the ECAP probe electrode. The relationship between the physiological channel
      interactions, spectral resolution in the local cochlear region, and vowel
      identification was evaluated. Results showed that (1) there was within- and
      across-subject variability in the widths of ECAP channel interaction functions
      and in narrowband SRD performance, (2) significant correlations were found
      between the widths of the ECAP functions and narrowband SRD thresholds, and
      between mean bandwidths of ECAP functions averaged across multiple probe
      electrodes and broadband SRD performance across subjects, and (3) the global
      spectral resolution reflecting the entire electrode array, not the local region,
      predicts vowel identification. 

PMID- 25373973
TI  - Sound source localization identification accuracy: bandwidth dependencies.
AB  - Sound source localization accuracy using a sound source identification task was
      measured in the front, right quarter of the azimuth plane as rms (root-mean
      square) error (degrees) for stimulus conditions in which the bandwidth (1/20 to 2
      octaves wide) and center frequency (250, 2000, 4000 Hz) of 200-ms noise bursts
      were varied. Tones of different frequencies (250, 2000, 4000 Hz) were also used.
      As stimulus bandwidth increases, there is an increase in sound source
      localization identification accuracy (i.e., rms error decreases). Wideband
      stimuli (>1 octave wide) produce best sound source localization accuracy (~6
      degrees -7 degrees  rms error), and localization accuracy for these wideband
      noise stimuli does not depend on center frequency. For narrow bandwidths (<1
      octave) and tonal stimuli, accuracy does depend on center frequency such that
      highest accuracy is obtained for low-frequency stimuli (centered on 250 Hz),
      worse accuracy for mid-frequency stimuli (centered on 2000 Hz), and intermediate
      accuracy for high-frequency stimuli (centered on 4000 Hz).

PMID- 25373972
TI  - Phase effects in masking by harmonic complexes: detection of bands of speech
      shaped noise.
AB  - When phase relationships between partials of a complex masker produce highly
      modulated temporal envelopes on the basilar membrane, listeners may detect speech
      information from temporal dips in the within-channel masker envelopes. This
      source of masking release (MR) is however located in regions of unresolved masker
      partials and it is unclear how much of the speech information in these regions is
      really needed for intelligibility. Also, other sources of MR such as glimpsing in
      between resolved masker partials may provide sufficient information from regions
      that disregard phase relationships. This study simplified the problem of speech
      recognition to a masked detection task. Target bands of speech-shaped noise were
      restricted to frequency regions containing either only resolved or only
      unresolved masker partials, as a function of masker phase relationships (sine or
      random), masker fundamental frequency (F0) (50, 100, or 200 Hz), and masker
      spectral profile (flat-spectrum or speech-shaped). Although masker phase effects
      could be observed in unresolved regions at F0s of 50 and 100 Hz, it was only at
      50-Hz F0 that detection thresholds were ever lower in unresolved than in resolved
      regions, suggesting little role of envelope modulations for harmonic complexes
      with F0s in the human voice range and at moderate level. 

PMID- 25373974
TI  - The effects of measurement error and vowel selection on the locus equation
      measure of coarticulation.
AB  - Effects on the slope of introducing error in the F2 Hz values in locus equations
      (LEs) and of using fewer than ten vowels were investigated. For each of the
      initial consonants /b, d, g/, 2000 simulated sets were generated using Monte
      Carlo techniques. The sets were altered with 50, 100, or 200 Hz error being
      randomly applied to each F2 value within a set. Selected vowels were then removed
      from the sets and the effects on the slopes were measured. Results suggest that
      the LE slopes are generally resistant to error and reduced number of vowels.
      Effects of adding 50 Hz of random error to the F2 values in sets using eight or
      ten vowels were minimal, yielding a mean absolute change in slope less than 0.07.

PMID- 25373975
TI  - A cross-dialectal acoustic comparison of vowels in Northern and Southern British
      English.
AB  - This study compares the duration and first two formants (F1 and F2) of 11 nominal
      monophthongs and five nominal diphthongs in Standard Southern British English
      (SSBE) and a Northern English dialect. F1 and F2 trajectories were fitted with
      parametric curves using the discrete cosine transform (DCT) and the zeroth DCT
      coefficient represented formant trajectory means and the first DCT coefficient
      represented the magnitude and direction of formant trajectory change to
      characterize vowel inherent spectral change (VISC). Cross-dialectal comparisons
      involving these measures revealed significant differences for the phonologically
      back monophthongs /alpha, o?, upsilon, u?/ and also /ze?/ and the diphthongs /ei,
      eupsilon, ai, oi/. Most cross-dialectal differences are in zeroth DCT
      coefficients, suggesting formant trajectory means tend to characterize such
      differences, while first DCT coefficient differences were more numerous for
      diphthongs. With respect to VISC, the most striking differences are that /u?/ is
      considerably more diphthongized in the Northern dialect and that the F2
      trajectory of /eupsilon/ proceeds in opposite directions in the two dialects.
      Cross-dialectal differences were found to be largely unaffected by the
      consonantal context in which the vowels were produced. The implications of the
      results are discussed in relation to VISC, consonantal context effects and speech
      perception. 

PMID- 25373976
TI  - Burst spectrum as a cue for the stop voicing contrast in American English.
AB  - Voicing contrasts in stop consonants are expressed by a constellation of acoustic
      cues. This study focused on a spectral cue present at burst onset in American
      English labial and coronal stops. Spectral shape was examined for word-initial,
      prevocalic stops of all three places of articulation in a laboratory production
      study and a large corpus of continuous read speech. Voiceless labial and coronal
      stops were found to have greater energy at higher frequencies in comparison to
      homorganic voiced stops, a difference that could not be attributed to aspiration
      in the voiceless stops or modal phonation in the voiced, while no consistent
      effect was found for dorsal stops. This pattern was found with various methods of
      spectral estimation (time-averaged and multitaper spectra) and measures of
      spectral energy concentration (center of gravity and spectral peak) for both
      linear and auditorily based frequency scales. Perceptual relevance of the
      spectral cue was tested in laboratory and online experiments with continua
      created by crossing burst shape and voice onset time. A trading relation was
      observed such that voiceless identifications were more likely for tokens with
      higher frequency bursts. Goodness ratings indicated that burst spectrum
      influences category typicality for voiceless stops even when voice onset time is
      unambiguous. 

PMID- 25373977
TI  - Analysis of vibratory states in phonation using spectral features of the
      electroglottographic signal.
AB  - The vocal folds can oscillate in several different ways, manifest to
      practitioners and clinicians as "registers" or "mechanisms," of which the two
      most often considered are modal voice and falsetto voice. Here these will be
      taken as instances of different "vibratory states," i.e., distinct quasi
      stationary patterns of vibration of the vocal folds. State transitions are common
      in biomechanical nonlinear oscillators, and they are often abrupt and impossible
      to predict exactly. Therefore, vibratory states are a source of confounding
      variation, for instance when acquiring a voice range profile (VRP). In the quest
      for a state-based, non-invasive VRP, a semi-automatic method based on the short
      term spectrum of the electroglottographic (EGG) signal was developed. The method
      identifies rapid vibratory state transitions, such as the modal-falsetto switch,
      and clusters the EGG data based on their similarities in the relative levels and
      phases of the lower frequency components. Productions of known modal and falsetto
      voice were accurately clustered by a Gaussian mixture model. When mapped into the
      VRP, this EGG-based clustering revealed connected regions of different vibratory
      sub-regimes in both modal and falsetto. 

PMID- 25373978
TI  - Vocal fold vibratory patterns in tense versus lax phonation contrasts.
AB  - This study explores the vocal fold contact patterns of one type of phonation
      contrast--the tense vs lax phonation contrasts of three Yi (Loloish) languages.
      These contrasts are interesting because neither phonation category is very
      different from modal voice, and because both phonations are largely independent
      of the languages' tonal contrasts. Electroglottographic (EGG) recordings were
      made in the field, and traditional EGG measures were derived. These showed many
      small but significant differences between the phonations, with tense phonation
      having greater contact quotients and briefer but slower changes in contact.
      Functional data analysis was then applied to entire EGG pulse shapes. The
      resulting first principal component was found to be mostly strongly related to
      the phonation contrasts, and correlated with almost all the traditional EGG
      measures. Unlike the traditional measures, however, this component also seems to
      capture differences in abruptness of contact. Furthermore, previously collected
      perceptual responses from native speakers of one of the languages correlated
      better with this component than with any other EGG measure or any acoustic
      measure. The differences between these tense and lax phonations are not large,
      but apparently they are consistent enough, and perceptually robust enough, to
      support this linguistic contrast.

PMID- 25373979
TI  - Perceptual consequences of changes in epilaryngeal area and shape.
AB  - The influence of epilaryngeal area on glottal flow and the acoustic signal has
      been described [Titze, J. Acoust. Soc. Am. 123, 2733-2749 (2008)], but it is not
      known how (or whether) changes in epilaryngeal area influence perceived voice
      quality. This study examined these relationships in a kinematic vocal tract
      model. Epilaryngeal constrictions and expansions were simulated at the levels of
      the aryepiglottic folds and the ventricular folds in the context of four glottal
      configurations representing normal vibration to severe vocal fold paralysis, for
      the three corner vowels /a/, /i/, and /u/. Minimum and maximum glottal flow,
      maximum flow declination rate, spectral slope, cepstral peak prominence, and the
      harmonics-to-noise ratio were measured, and listeners completed a perceptual sort
      and-rate task for all samples. Epilaryngeal constriction and expansion caused
      salient differences in voice quality. The location of constriction was also
      perceivable. Vowels simulated with aryepiglottic constriction demonstrated lower
      maximum airflow and less noise than the other epilaryngeal shapes, and listeners
      consistently perceived them as distinct from other stimuli. Acoustic differences
      decreased with increasing severity of simulated paralysis. Results of
      epilaryngeal constriction and expansion were similar for /a/ and /i/, and
      produced slightly different patterns for /u/. 

PMID- 25373980
TI  - Toddlers' ability to map the meaning of new words in multi-talker environments.
AB  - Whether in a noisy daycare center, home, or classroom, many of the environments
      children are exposed to are, undoubtedly, not acoustically ideal for speech
      processing. Yet, somehow, these toddlers are still able to acquire vocabularies
      consisting of hundreds of words. The current study explores the effect of
      background speech noise on children's early word learning (specifically, their
      ability to map a label onto an object). Three groups of children aged 32-36
      months were taught two new words either in quiet, or in the presence of multi
      talker babble at a +5 or 0 dB signal-to-noise ratio (SNR). They were then tested
      on their learning of these new word-to-object mappings. Children showed similar
      accuracy in all three conditions, suggesting that even at a 0 dB SNR, children
      were successfully able to learn new words. 

PMID- 25373981
TI  - Age mitigates the correlation between cognitive processing speed and audio-visual
      asynchrony detection in speech.
AB  - Cognitive processing speed, hearing acuity, and audio-visual (AV) experience have
      been suggested to influence AV asynchrony detection. Whereas the influence of
      hearing acuity and AV experience have been explored to some extent, the influence
      of cognitive processing speed on perceived AV asynchrony has not been directly
      tested. Therefore, the current study investigates the relationship between
      cognitive processing speed and AV asynchrony detection in speech and, with
      hearing acuity controlled, assesses whether age-related AV experience mitigates
      the strength of this relationship. The cognitive processing speed and AV
      asynchrony detection by 20 young adults (20-30 years) and 20 middle-aged adults
      (50-60 years) were measured using auditory, visual and AV recognition reaction
      time tasks, and an AV synchrony judgment task. Strong correlations between audio,
      visual, and AV reaction times and AV synchrony window size were found for young
      adults, but not for middle-aged adults. These findings suggest that although
      cognitive processing speed influences AV asynchrony detection in speech, the
      strength of the relationship is seemingly reduced by AV experience. 

PMID- 25373982
TI  - Effects of language experience and expectations on attention to consonants and
      tones in English and Mandarin Chinese.
AB  - Both long-term native language experience and immediate linguistic expectations
      can affect listeners' use of acoustic information when making a phonetic
      decision. In this study, a Garner selective attention task was used to
      investigate differences in attention to consonants and tones by American English
      speaking listeners (N = 20) and Mandarin Chinese-speaking listeners hearing
      speech in either American English (N = 17) or Mandarin Chinese (N = 20). To
      minimize the effects of lexical differences and differences in the linguistic
      status of pitch across the two languages, stimuli and response conditions were
      selected such that all tokens constitute legitimate words in both languages and
      all responses required listeners to make decisions that were linguistically
      meaningful in their native language. Results showed that regardless of ambient
      language, Chinese listeners processed consonant and tone in a combined manner,
      consistent with previous research. In contrast, English listeners treated tones
      and consonants as perceptually separable. Results are discussed in terms of the
      role of sub-phonemic differences in acoustic cues across language, and the
      linguistic status of consonants and pitch contours in the two languages. 

PMID- 25373983
TI  - Perception of touch quality in piano tones.
AB  - Both timbre and dynamics of isolated piano tones are determined exclusively by
      the speed with which the hammer hits the strings. This physical view has been
      challenged by pianists who emphasize the importance of the way the keyboard is
      touched. This article presents empirical evidence from two perception experiments
      showing that touch-dependent sound components make sounds with identical hammer
      velocities but produced with different touch forms clearly distinguishable. The
      first experiment focused on finger-key sounds: musicians could identify pressed
      and struck touches. When the finger-key sounds were removed from the sounds, the
      effect vanished, suggesting that these sounds were the primary identification
      cue. The second experiment looked at key-keyframe sounds that occur when the key
      reaches key-bottom. Key-bottom impact was identified from key motion measured by
      a computer-controlled piano. Musicians were able to discriminate between piano
      tones that contain a key-bottom sound from those that do not. However, this
      effect might be attributable to sounds associated with the mechanical components
      of the piano action. In addition to the demonstrated acoustical effects of
      different touch forms, visual and tactile modalities may play important roles
      during piano performance that influence the production and perception of musical
      expression on the piano. 

PMID- 25373984
TI  - Statistical analysis of North Atlantic right whale (Eubalaena glacialis) signal
      trains in Cape Cod Bay, spring 2012.
AB  - Statistical characteristics of signal trains produced by North Atlantic right
      whales (NARW) during the winter and early spring in Cape Cod Bay, MA are
      described. Data analysis was based on four days of acoustic recordings that were
      obtained with synchronized hydrophones. Based on temporal and geographical
      clustering of detected signals, 7264 NARW sounds were identified and associated
      with 559 signal trains. The detected signals were assigned to four classes of
      narrowband tonal calls--upcalls, downcalls, complex, and high frequency, and two
      classes of wideband sounds--gunshots and complex. Empirical distributions of the
      number of signals in trains, total duration of trains, the positions of NARW, and
      signal classes are presented. Results indicate that 68.9% of all signal trains
      consisted of 10 or fewer signals. Low and high frequency tonals that lacked
      wideband sounds formed 69.1% of trains; 5.0% of trains lacked tonals. Trains
      consisting of only upcalls comprised 44.2% of all detected trains. Because 18.3%
      of trains contained no upcalls, using detectors that identify all signal classes
      would improve right whale detection.

PMID- 25373985
TI  - Vocal repertoire of the social giant otter.
AB  - According to the "social intelligence hypothesis," species with complex social
      interactions have more sophisticated communication systems. Giant otters
      (Pteronura brasiliensis) live in groups with complex social interactions. It is
      likely that the vocal communication of giant otters is more sophisticated than
      previous studies suggest. The objectives of the current study were to describe
      the airborne vocal repertoire of giant otters in the Pantanal area of Brazil, to
      analyze call types within different behavioral contexts, and to correlate vocal
      complexity with level of sociability of mustelids to verify whether or not the
      result supports the social intelligence hypothesis. The behavior of nine giant
      otters groups was observed. Vocalizations recorded were acoustically and
      statistically analyzed to describe the species' repertoire. The repertoire was
      comprised by 15 sound types emitted in different behavioral contexts. The main
      behavioral contexts of each sound type were significantly associated with the
      acoustic variable ordination of different sound types. A strong correlation
      between vocal complexity and sociability was found for different species,
      suggesting that the communication systems observed in the family mustelidae
      support the social intelligence hypothesis. 

PMID- 25373986
TI  - Multi-echo processing by a bottlenose dolphin operating in "packet" transmission
      mode at long range.
AB  - Bottlenose dolphins performing echolocation tasks at long ranges may utilize a
      transmission mode where bursts, or "packets," of echolocation clicks are emitted
      rather than single clicks. The clicks within each packet are separated by time
      intervals well below the two-way travel time, while the packets themselves are
      emitted at intervals greater than the two-way travel time. Packet use has been
      shown to increase with range; however, the exact function of packets and the
      advantages gained by their utilization remain unknown. In this study, the
      capability for dolphins to utilize multi-echo processing within packets of echoes
      was investigated by manipulating the number of available echoes within each
      packet as a dolphin performed a long-range echolocation task. The results showed
      an improvement in detectability with an increase in the number of echoes in each
      packet and suggest that packet use is an adaptation to allow multi-echo
      processing at long ranges without introducing range ambiguity. 

PMID- 25373991
TI  - Auditory motivated front-end for noisy speech using spectro-temporal modulation
      filtering.
AB  - The robustness of the human auditory system to noise is partly due to the peak
      preserving capability of the periphery and the cortical filtering of spectro
      temporal modulations. In this letter, a robust speech feature extraction scheme
      is developed that emulates this processing by deriving a spectrographic
      representation that emphasizes the high energy regions. This is followed by a
      modulation filtering step to preserve only the important spectro-temporal
      modulations. The features derived from this representation provide significant
      improvements for speech recognition in noise and language identification in radio
      channel speech. Further, the experimental analysis shows congruence with human
      psychophysical studies. 

PMID- 25373992
TI  - Directionality of the ambient noise field in an Arctic, glacial bay.
AB  - The directionality of ambient noise in an Arctic tidewater glacier bay was
      measured using two horizontally spaced, broadband hydrophones. Segments of noise
      were divided into two frequency bands and analyzed for arrival angle. These data
      show that different classes of source radiate noise in distinct spectral bands
      and are spatially diverse. A previously unidentified source, the interaction of
      surface gravity waves with underside of ice ledges at the periphery of icebergs,
      is described. The generation of noise by ice-wave interaction suggests that
      surface waves should be measured if ambient noise is to be used to monitor ice
      dynamics in glacial fjords. 

PMID- 25373993
TI  - The effects of wood variability on the free vibration of an acoustic guitar top
      plate.
AB  - A finite element model of a bare top plate with braces and a bridge plate was
      created using orthotropic material properties. The natural variation of the wood
      properties including dependence on moisture content was also determined. The
      simulated modes were then compared to experimentally obtained modes from top
      plate prototypes. Uncertainty analysis was also performed to determine the
      statistical bound of natural variability between wood samples. The natural
      frequencies of the model fall within the computed error bound. These results
      reinforce the importance of obtaining accurate material properties for acoustic
      guitar modeling. 

PMID- 25373994
TI  - Geoacoustic inversion of ship radiated noise in shallow water using data from a
      single hydrophone.
AB  - The Centre for Maritime Research and Experimentation conducted a geoacoustic
      inverse experiment in the Mediterranean Sea in the summer of 2012. Among the
      objectives was to employ an autonomous underwater vehicle to collect acoustic
      data to invert for properties of the seafloor. Inversion results for the
      compression wave speed in the bottom and the source spectrum of the R/V Alliance
      during a close approach to the bottom moored vehicle are presented. The estimated
      wave speed was 1529 m/s (sigma=10). The source spectrum of the Alliance was
      estimated across more than six octaves of frequency.

PMID- 25373995
TI  - A computational study of the effect of intraglottal vortex-induced negative
      pressure on vocal fold vibration.
AB  - Recent studies reported the formation of intraglottal vortices for medium and
      high subglottal pressures in excised-larynx experiments, and hypothesized that
      the suction force created by these vortices might affect vocal fold vibration.
      However, high subglottal pressures often lead to large vocal fold elastic recoil
      forces, and it is unclear if the vortex-induced suction force is large enough
      compared with the elastic recoil force to have noticeable effects on vocal fold
      vibration. In this study, the validity of this hypothesis was examined using a
      computational model. The results suggest that intraglottal vortices might only
      have small effects on vocal fold vibration. 

PMID- 25373996
TI  - Normal incidence measurement in a subaqueous sand dune field in the South China
      Sea.
AB  - Regions with subaqueous sand dunes have been discovered on the upper continental
      slope of the northern South China Sea. These large subaqueous sand dunes are
      expected to cause errors in the measurement of normal incidence reflection. This
      letter presents experiment results of two normal incidence survey tracks
      conducted in 2013, and the errors in reflection coefficient estimation and the
      resulting sediment properties induced by sand dune bedforms. The results
      demonstrate that the reflected energy is focused and scattered by different parts
      of sand dune bedforms and that they produce significant variation in the
      estimated reflection coefficients and the inverted geoacoustic properties. 

PMID- 25373997
TI  - Modest, reliable spectral peaks in preceding sounds influence vowel perception.
AB  - When a spectral property is reliable across an acoustic context and subsequent
      vowel target, perception deemphasizes this cue and shifts toward less
      predictable, more informative cues. This phenomenon (auditory perceptual
      calibration) has been demonstrated for reliable spectral peaks +20 dB or larger,
      but psychoacoustic findings predict sensitivity to more modest spectral peaks.
      Listeners identified vowel targets following a sentence with a reliable +2 to +15
      dB spectral peak centered at F2 of the vowel. Vowel identifications weighted F2
      significantly less when reliable peaks were at least +5 dB. Results demonstrate
      high sensitivity to reliable acoustic properties in the sensory environment.

PMID- 25373999
TI  - Retraction. Adseverin knockdown inhibits osteoclastogenesis in RAW264.7 cells.

PMID- 25373998
TI  - Food activities and identity maintenance in old age: a systematic review and meta
      synthesis.
AB  - OBJECTIVES: Services provided to older people should be developed based on active
      ageing policies. Nutrition is one aspect of active ageing, but little is known
      about how food activities contribute to psychological well-being in later life.
      This is a systematic review of qualitative and quantitative research that answers
      the question 'What is known about the relationship between food activities and
      the maintenance of identities in old age?'. METHODS: We followed the preferred
      reporting items for systematic reviews and meta-analyses guidelines and used
      quality assessment parameters to complete a systematic review and narrative
      synthesis. Academic Search Premier, MEDLINE, CINAHL Plus, and PsycINFO databases
      were searched. RESULTS: We initially identified 8016 articles, of which 167 full
      text articles were screened for inclusion. Twenty-two articles were included in
      the review. There was moderate evidence from nine qualitative and two
      quantitative studies, of variable quality, that food activities contribute to the
      maintenance of women's gendered identities, the ethnic identities of men and
      women, and community identities. There was moderate evidence from 10 qualitative
      studies, of variable quality, that a change in food choice and deteriorating
      health changed food activity participation. These changes threatened identities.
      Most studies included both younger adults and older adults. CONCLUSION: In later
      life, there are many life experiences leading to change. Further research is
      needed to develop understanding of how identity and mental well-being are
      maintained, despite changes in everyday activities like cooking and eating. This
      may enable health care professionals to meet psychological needs alongside
      biological needs during nutritional interventions.

PMID- 25374001
TI  - Triple negative breast cancer - BCL2 in prognosis and prediction. Review.
AB  - BACKGROUND: Breast cancer (BC), the most frequent malignancy in women worldwide,
      is currently diagnosed in about 1.4 million female patients annually.
      Approximately 10-20% of BC is represented by triple negative breast cancer (TNBC)
      which is aggressive, the prognosis is poor and patients cannot benefit from
      targeted treatment based on hormonal or HER2 receptors. For this reason, search
      for markers that can predict the efficacy of chemotherapy in TNBC is a priority.
      METHODS AND RESULTS: This review focuses on BCL2 protein as a prognostic marker
      in TNBC and its potential as a predictor of sensitivity to chemotherapy.
      CONCLUSION: BCL2 protein expression is a positive prognostic factor in BC. Better
      survival of patients with BCL2 positivity (BCL2+) has been explained by the
      correlation with estrogen receptor positive (ER+) status. BCL2+ is however not
      simply a surrogate marker for ER+. Moreover, BCL2 protein expression is also a
      positive prognostic marker in the TNBC subgroup. We and others show, that low
      BCL2 expression was associated with good outcome of TNBC patients treated with
      both adjuvant and neoadjuvant anthracycline-based chemotherapy. On the other
      hand, recent studies have shown that a subset of TNBC patients may benefit from
      the classical adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil)
      regimen. Given the heterogeneity of TNBC there is an urgent need to find and
      validate the sensitivity predictors to these regimens making them usable in
      clinical practice. BCL2 enrichment has been described in the mesenchymal stem
      like (MSL) TNBC subgroup.

PMID- 25374000
TI  - Determinants and effects of positive surgical margins after prostatectomy on
      prostate cancer mortality: a population-based study.
AB  - BACKGROUND: The objective of this population-based study was to assess patient,
      physician and tumour determinants associated with positive surgical margins after
      prostatectomy, and to assess the effects of positive surgical margins on prostate
      cancer-specific survival. METHODS: We included 1'254 prostate cancer patients
      recorded at the Geneva Cancer Registry who had radical prostatectomy during 1990
      2008. To assess factors associated with positive margins, we used logistic
      regression. We assessed the effects of positive margins on prostate cancer
      specific survival by Cox proportional hazard models accounting for numerous other
      prognostics factors including prostate and tumour volume, the total percentage of
      tumour, radiotherapy, surgical approach and surgeon's caseload. RESULTS: Among
      men undergoing prostatectomy, 479 (38%) had positive margins. In the multivariate
      logistic regression analysis, period, clinical- and pathological T stage,
      Prostate Specific Antigen (PSA) level, Gleason score and percentage of tumour in
      the prostate were significantly associated to positive margins. Ten-year prostate
      cancer-specific survival was 96.6% for the negative margins group and 92.0% for
      the positive margins group (log rank p = 0.008). In the Cox survival analysis
      adjusted for tumour characteristics, surgical margin status per se was not an
      independent prognostic factor while age, pathological T, PSA level and Gleason
      score remained associated with prostate cancer-specific survival. CONCLUSIONS:
      More aggressive tumour characteristics were strong determinants for positive
      margins. Furthermore, surgical margin status per se was not an independent
      prognostic factor for prostate cancer-specific survival after adjusting by the
      gravity of the disease in the multivariate analysis.

PMID- 25374002
TI  - Cholesterol-lowering effect of rice bran protein containing bile acid-binding
      proteins.
AB  - Dietary plant protein is well known to reduce serum cholesterol levels. Rice bran
      is a by-product of rice milling and is a good source of protein. The present
      study examined whether feeding rats a high-cholesterol diet containing 10% rice
      bran protein (RBP) for 10 d affected cholesterol metabolism. Rats fed dietary RBP
      had lower serum total cholesterol levels and increased excretion of fecal
      steroids, such as cholesterol and bile acids, than those fed dietary casein. In
      vitro assays showed that RBP strongly bound to taurocholate, and inhibited the
      micellar solubility of cholesterol, compared with casein. Moreover, the bile acid
      binding proteins of the RBP were eluted by a chromatographic column conjugated
      with cholic acid, and one of them was identified as hypothetical protein
      OsJ_13801 (NCBI accession No. EAZ29742) using MALDI-TOF mass spectrometry
      analysis. These results suggest that the hypocholesterolemic action of the RBP
      may be caused by the bile acid-binding proteins. 

PMID- 25374004
TI  - Understanding the mechanisms, identifying and treating prolonged epileptic
      seizures.

PMID- 25374003
TI  - Clinical efficacy of radical nephrectomy versus nephron-sparing surgery on
      localized renal cell carcinoma.
AB  - BACKGROUND: The aim of the present study was to compare the clinical efficacy of
      radical nephrectomy (RN) with nephron-sparing surgery (NSS) in treating patients
      with localized renal cell carcinoma (RCC). METHODS: The literature search was
      performed in PubMed, MEDLINE Springer, Elsevier Science Direct, Cochrane Library,
      and Google Scholar up to December 2012. The software Review Manager 5.1 and the
      STATA software package v.11.0 were used for analyses. The odds ratios (ORs) and
      its 95% confidence interval (95% CI) were calculated for comparison. Subgroup
      analyses were performed based on the tumor size of RCC. RESULTS: In total, 10
      studies with 10,174 RCC patients (7,050 treated with RN and 3,124 treated with
      NSS) were selected. The pooled estimate (OR = 1.58, 95% CI = 1.15-2.15, P =
      0.004) showed a significantly lower rate of cancer-specific deaths in the
      patients treated with NSS compared to RN. However, no statistically significant
      differences were found in the rate of tumor recurrence (OR = 0.84, 95% CI = 0.67
      1.06, P = 0.14) and complications (OR = 0.91, 95% CI = 0.51-1.63, P = 0.74)
      between the patients treated with NSS and RN. In addition, all the subgroup
      analyses presented consistent results with the overall analyses. CONCLUSIONS: NSS
      had no significantly different from RN in tumor recurrence and complications for
      localized RCC. However, the significantly lower rate of cancer-specific deaths
      supported the use of NSS not only for RCC with tumor size >4.0 cm but also for
      tumor sizes <=4.0 cm compared with RN.

PMID- 25374005
TI  - Genomic prediction based on data from three layer lines using non-linear
      regression models.
AB  - BACKGROUND: Most studies on genomic prediction with reference populations that
      include multiple lines or breeds have used linear models. Data heterogeneity due
      to using multiple populations may conflict with model assumptions used in linear
      regression methods. METHODS: In an attempt to alleviate potential discrepancies
      between assumptions of linear models and multi-population data, two types of
      alternative models were used: (1) a multi-trait genomic best linear unbiased
      prediction (GBLUP) model that modelled trait by line combinations as separate but
      correlated traits and (2) non-linear models based on kernel learning. These
      models were compared to conventional linear models for genomic prediction for two
      lines of brown layer hens (B1 and B2) and one line of white hens (W1). The three
      lines each had 1004 to 1023 training and 238 to 240 validation animals.
      Prediction accuracy was evaluated by estimating the correlation between observed
      phenotypes and predicted breeding values. RESULTS: When the training dataset
      included only data from the evaluated line, non-linear models yielded at best a
      similar accuracy as linear models. In some cases, when adding a distantly related
      line, the linear models showed a slight decrease in performance, while non-linear
      models generally showed no change in accuracy. When only information from a
      closely related line was used for training, linear models and non-linear radial
      basis function (RBF) kernel models performed similarly. The multi-trait GBLUP
      model took advantage of the estimated genetic correlations between the lines.
      Combining linear and non-linear models improved the accuracy of multi-line
      genomic prediction. CONCLUSIONS: Linear models and non-linear RBF models
      performed very similarly for genomic prediction, despite the expectation that non
      linear models could deal better with the heterogeneous multi-population data.
      This heterogeneity of the data can be overcome by modelling trait by line
      combinations as separate but correlated traits, which avoids the occasional
      occurrence of large negative accuracies when the evaluated line was not included
      in the training dataset. Furthermore, when using a multi-line training dataset,
      non-linear models provided information on the genotype data that was
      complementary to the linear models, which indicates that the underlying data
      distributions of the three studied lines were indeed heterogeneous.

PMID- 25374006
TI  - Integrative self-sorting: a versatile strategy for the construction of complex
      supramolecular architecture.
AB  - Large protein-sized synthetic supramolecular architecture is rare and certainly
      has not yet achieved the structural and functional complexity of biomolecules. As
      multiple, identical copies of a few building blocks are repetitively used, a
      highly symmetrical architecture results with limitations in function. In marked
      contrast, functional structures in nature are often assembled with high geometric
      precision from many different building blocks. They cooperate in a complex way
      realizing energy conversion, mechanical motion or transport phenomena. Beyond
      self-assembly, the structurally and functionally complex biomolecular machines
      rely on self-sorting to correctly position all subunits through orthogonal
      recognition sites. Mimicking such self-sorting processes is a promising strategy
      for supramolecular synthesis - resulting in higher structural complexity and
      promising access to a more sophisticated function. The term "integrative self
      sorting" was coined to describe the strategy to form well-defined assemblies with
      well-controlled subunit positions. The key process is the incorporation of two or
      more orthogonal binding motifs into at least some of the subunits. Modularity and
      programmability based on orthogonal yet similar binding motifs generate diversity
      and complexity. Integrative self-sorting is thus inherently related to systems
      chemistry. Depending on the individual binding motifs, (multi-)stimuli
      responsiveness can be achieved. When different recognition events en route to the
      final assembly occur on significantly different time scales, kinetic pathway
      selection is observed. In this account, we review the modularity,
      programmability, and emergent properties of integrative self-sorting, emphasizing
      its utility and perspective for complex supramolecular architectures. 

PMID- 25374007
TI  - In vitro selection of a peptide aptamer that changes fluorescence in response to
      verotoxin.
AB  - A peptide aptamer that changes fluorescence upon binding to verotoxin was
      selected in vitro using ribosome display with a tRNA carrying an environment
      sensitive fluorescent probe. The aptamer specifically bound to verotoxin with a
      dissociation constant (K d) of 3.94 +/- 1.6 uM, and the fluorescence decreased by
      78% as the verotoxin concentration was increased. The selected peptide can be
      used for detection of verotoxin.

PMID- 25374008
TI  - Oral vaccination of mice with Tremella fuciformis yeast-like conidium cells
      expressing HBsAg.
AB  - Tremella fuciformis yeast-like conidium (YLC) cells were transformed by co
      cultivation with Agrobacterium cells harboring the hepatitis B surface antigen
      (HBsAg) gene construct under the control of the CaMV35S promoter. Integration of
      HBsAg DNA into the YLC genome was confirmed by PCR and dot-blot hybridization.
      Immunoblotting verified expression of the recombinant protein. Oral
      administration of YLC cells expressing HBsAg in mice significantly increased anti
      HBsAg antibody titer levels using a double prime-boost strategy that combined
      parenteral and oral HBsAg boosters. 

PMID- 25374009
TI  - Distribution of serum erythropoietin levels in Japanese patients with
      myelodysplastic syndromes.
AB  - Erythropoiesis-stimulating agents (ESAs) are used to ameliorate anemia in lower
      risk myelodysplastic syndromes (MDS). Serum erythropoietin (EPO) level <500 IU/L
      is widely accepted as a major predictive factor for response to ESAs. However,
      few data about EPO levels in the Japanese population are available. We therefore
      evaluated distribution of serum EPO levels in Japanese patients with MDS. Forty
      three cases were analyzed; 30 were classified as lower-risk MDS (low or
      intermediate-1 by the international prognostic scoring system). Twenty-two cases
      were transfusion dependent. The overall median hemoglobin level was 7.7 g/dL. The
      median value of serum EPO was 254 IU/L (range: 16.4-23,000). Serum EPO levels had
      a strong inverse correlation with hemoglobin levels, and a significantly larger
      proportion of patients showed high EPO levels (>500 IU/L) in the transfusion
      dependent group. In the higher-risk group, no significant correlation between EPO
      and hemoglobin was observed. Regression analyses showed that serum EPO of 500
      IU/L corresponds to 8.29 g/dL of hemoglobin in lower-risk MDS. The results
      indicate that patients with hemoglobin levels of 8.0 g/dL or more, who are still
      transfusion independent, may be good candidates for ESA treatment.

PMID- 25374011
TI  - Evaluation on clot buster activity of staphylokinase from Staphylococcus sp.
AB  - Thrombolytic agents play a major role in the treatment of cardiovascular
      diseases. Streptokinase is the prominently commercialized thrombolytic drug used
      for the treatment of cardiovascular diseases. The later studies on staphylokinase
      (SaK) showed promising results as an alternative fibrinolytic drug. The present
      study explores the isolation, production and purification of SaK producing
      Staphylococcus sp. from milk samples. The potent isolate MSA4 of Staphylococcus
      sp. was selected for production and purification of SaK. The total activity and
      specific activity of purified staphylokinase was found to be 1266 IU mL(-1) and
      815.5 IU mg(-1), respectively. The partially purified enzyme was lysed the
      euglobulin clot completely within 18 h of incubation and the purified enzyme
      showed 79% of blood clot lysis activity. 

PMID- 25374010
TI  - Self in vivo production of a synthetic biological drug CTLA4Ig using a minicircle
      vector.
AB  - Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein
      (CTLA4Ig, abatacept) is a B7/CD28 costimulation inhibitor that can ward off the
      immune response by preventing the activation of naive T cells. This therapeutic
      agent is administered to patients with autoimmune diseases such as rheumatoid
      arthritis. Its antiarthritic efficacy is satisfactory, but the limitations are
      the necessity for frequent injection and high cost. Minicircles can robustly
      express the target molecule and excrete it outside the cell as an indirect method
      to produce the protein of interest in vivo. We inserted the sequence of abatacept
      into the minicircle vector, and by successful in vivo injection the host was able
      to produce the synthetic protein drug. Intravenous infusion of the minicircle
      induced spontaneous production of CTLA4Ig in mice with collagen-induced
      arthritis. Self-produced CTLA4Ig significantly decreased the symptoms of
      arthritis. Injection of minicircle CTLA4Ig regulated Foxp3(+) T cells and Th17
      cells. Parental and mock vectors did not ameliorate arthritis or modify the T
      cell population. We have developed a new concept of spontaneous protein drug
      delivery using a minicircle vector. Self in vivo production of a synthetic
      protein drug may be useful when biological drugs cannot be injected because of
      manufacturing or practical problems. 

PMID- 25374012
TI  - Emerging therapy options in heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening thrombotic
      complication of heparin, which is the result of platelet activation by anti
      PF4/heparin antibodies. With lepirudin and danaparoid no longer available in the
      US, treatment options are limited to argatroban, fondaparinux (off-label use) and
      bivalirudin (for patients undergoing percutaneous coronary intervention). Both
      argatroban and bivalirudin are parenteral drugs and require close monitoring and
      hospitalization. Fondaparinux is contraindicated in patients with significant
      renal impairment and is associated with a small risk of HIT. Anticoagulants
      approved for thromboprophylaxis and management of thromboembolic conditions such
      as rivaroxaban, dabigatran, and apixaban have fixed oral dose, rapid onset of
      action and does not require monitoring. These novel agents do not interact with
      anti-PF4/heparin antibody and offer attractive therapy options for HIT. Their
      utility in HIT has been supported by a few clinical reports, however, larger
      studies are needed before they can be utilized in clinical practice. Therapeutic
      plasma exchange has been utilized with some success in patients with HIT, who
      need heparin reexposure for cardiac surgery but their safety and efficacy needs
      further exploration. 2-O, 3-O desulfated heparin, which lacks any anticoagulant
      effect, has been shown to reduce the development of HIT in murine models.
      Finally, novel targets based on the molecular pathogenesis of HIT are being
      studied for therapeutic drug development. We hope that the availability of novel
      therapies in the future will expand the options available for the management of
      HIT. 

PMID- 25374013
TI  - Serpin regulation of fibrinolytic system: implications for therapeutic
      applications in cardiovascular diseases.
AB  - Fibrinolysis is the ultimate outcome of a cascade of enzymatic reactions in which
      serine proteases such as plasmin, tissue plasminogen activator (tPA), and
      urokinase plasminogen activator (uPA) are the key players. Plasmin degrades
      fibrin into soluble fibrin degradation products. The tPA-mediated plasminogen
      activation is mainly involved in the dissolution of fibrin in the circulating
      blood whereas the uPA binds to a specific cellular receptor, resulting in an
      enhanced activation of cell membrane bound plasminogen. These proteases are
      regulated by serine protease inhibitors (serpins). Serpin-mediated regulation may
      occur either at the level of plasmin, mainly by alpha2-antiplasmin (alpha2-AP) or
      at the level of the PAs, mainly by plasminogen activator inhibitor -1 (PAI-1).
      Other serpins may also be involved including plasminogen activator inhibitor -2
      and -3 (PAI-2 and PAI-3), protease nexin-1 (PN-1), C1-inhibitor (C1-INH),
      placental thrombin inhibitor (PTI), neuroserpin, and yukopin. The serpin-protease
      reactions serve as potential platforms to develop therapeutics for the treatment
      and prevention of cardiovascular diseases such as thrombosis and hemorrhage. This
      review will describe key serpins involved in the regulation of fibrinolytic
      system, particularly alpha2-AP and PAI-1, with the focus on their biochemical and
      biophysical aspects, the pathologies related to their dysfunction or deficiency,
      their therapeutic roles, and their reported cofactors or modulators. 

PMID- 25374014
TI  - Reduced beta-2-glycoprotein I inhibits hypoxia-induced retinal angiogenesis in
      neonatal mice through the vascular endothelial growth factor pathway.
AB  - beta-2-glycoprotein I (beta2GPI), also known as apolipoprotein H, is a
      phospholipid-binding plasma protein consisting of five homologous repeated units.
      beta2GPI downregulates vascular endothelial growth factor (VEGF) signaling
      pathways and inhibits angiogenesis in vitro. However, the in vivo roles and
      effectors of reduced beta2GPI and beta2GPI in retinal angiogenesis are still not
      fully understood. In this study, an oxygen-induced retinopathy model was used to
      investigate the effects of reduced beta2GPI and beta2GPI, and to monitor the
      expression of VEGF, VEGF receptor (VEGFR) 1, VEGFR-2 and hypoxia-inducible factor
      1 (HIF-1) mRNA and the phosphorylation of extracellular signal-regulated kinase
      (ERK) and Akt. The data showed that both beta2GPI and reduced beta2GPI inhibited
      retinal angiogenesis and suppressed the expression of VEGF, VEGFR-1, VEGFR-2, HIF
      1, phosphorylated- (p-) ERK and p-Akt. The effects of reduced beta2GPI were
      significantly stronger than those of beta2GPI. In conclusion, this study showed
      that beta2GPI and reduced beta2GPI could inhibit retinal angiogenesis by
      downregulating the expression of VEGF and its downstream targets. This suggests
      that beta2GPI and reduced beta2GPI may have potential anti-angiogenic activity in
      vivo.

PMID- 25374015
TI  - Downregulation of nitric oxide by electroacupuncture against hypoxic-ischemic
      brain damage in rats via nuclear factor-kappaB/neuronal nitric oxide synthase.
AB  - The present study aimed to investigate the role of nitric oxide (NO) against
      perinatal hypoxic-ischemic brain damage (HIBD) in rats by electroacupuncture (EA)
      and to examine its potential neuroprotective mechanism. NO content, the number of
      positive cells, neuronal nitric oxide synthase (nNOS) and nuclear factor-kappaB
      (NF-kappaB) in rat cortex cells were determined. The results demonstrated that
      treatment with EA significantly downregulated the NO content in the cortex cells
      (*P<0.05, **P<0.01, compared with the control groups) and alleviated cell damage
      in the cortex of rats with HIBD. The activator, S-adenosyl-L-methionine and the
      inhibitor, hydroxylamine of cystathionine-beta-synthase (CBS), aggravated and
      remitted the hypoxic damage in the cortex cells, respectively. In addition,
      treatment with EA significantly downregulated the expression of nNOS and NF
      kappaB in the rat cortex cells (*P<0.05, **P<0.01, compared with the control
      groups). The results also indicated that treatment with EA downregulated the NO
      content of cortical cells against HIBD via the NF-kappaB/nNOS pathway and further
      implied that the hydrogen sulfide/CBS system may be involved in the process. The
      present study provided a significant reference for the prevention and treatment
      of HIBD using the EA technique and also described a novel protective mechanism. 

PMID- 25374016
TI  - Association between Ambient Air Pollution and Outpatient Visits for Acute
      Bronchitis in a Chinese City.
AB  - OBJECTIVE: To investigate the short-term association between outdoor air
      pollution and outpatient visits for acute bronchitis, which is a rare subject of
      research in the mainland of China. METHODS: A time-series analysis was conducted
      to examine the association of outdoor air pollutants with hospital outpatient
      visits in Shanghai by using two-year daily data (2010-2011). RESULTS: Outdoor air
      pollution was found to be associated with an increased risk of outpatient visits
      for acute bronchitis in Shanghai. The effect estimates of air pollutants varied
      with the lag structures of the concentrations of the pollutants. For lag06, a 10
      MUg/m(3) increase in the concentrations of PM10, SO(2), and NO(2) corresponded to
      0.94% (95% CI: 0.83%, 1.05%), 11.12% (95% CI: 10.76%, 11.48%), and 4.84% (95% CI:
      4.49%, 5.18%) increases in hospital visits for acute bronchitis, respectively.
      These associations appeared to be stronger in females (P<0.05). Between-age
      differences were significant for SO(2) (P<0.05), and between-season differences
      were also significant for SO(2) (P<0.05). CONCLUSION: Our analyses have provided
      the first evidence that the current air pollution level in China has an effect on
      acute bronchitis and that the rationale for further limiting air pollution levels
      in Shanghai should be strengthened.

PMID- 25374017
TI  - Detection of human bocavirus in children with acute respiratory tract infections
      in Lanzhou and Nanjing, China.
AB  - OBJECTIVE: The aim of this study was to explore the prevalent characteristics of
      HBoV1 and its co-infection. METHODS: PCR was used to detect HBoV1-DNA (HBoV1) and
      other viruses. A multivariate logistic regression model was used to explore
      possibility of co-detected for related viruses. RESULTS: The positivity rates in
      Nanjing and Lanzhou were 9.38% (74/789) and 11.62% (161/1386), respectively
      (P>0.05). The HBoV1 positive group was younger than negative group (P<0.05).
      Seasonal differences were noted, with a higher frequency of infection in December
      and July. HBoV1-positive children [72.34% (169/235)] were co-infected with other
      respiratory viruses. Multifactorial analysis showed no correlations between HBoV1
      and the clinical classification, region, gender, age, or treatment as an
      outpatient or in a hospital. Correlations were identified between HBoV1
      infections with ADV (OR=1.53, 95% CI 1.03-2.28), RSV (OR=0.71, 95% CI 0.52-0.98),
      and IFVA (OR=1.77, 95% CI 1.00-3.13). CONCLUSION: Presence of HBoV1 in
      nasopharyngeal aspirates did not correlate with region or gender, although the
      prevalence of HBoV1 was higher in younger children. There were no correlations
      between HBoV1 and other variables, except for the season and ADV, RSV, or IFVA
      infections.

PMID- 25374018
TI  - Diversity and distribution of host animal species of hantavirus and risk to human
      health in Jiuhua mountain area, China.
AB  - OBJECTIVE: To investigate the diversity and the distribution of host animal
      species of hantavirus and the effect on human health in Jiuhua Mountain area,
      China. METHODS: The host animal species of hantavirus was surveyed by using the
      trap method and the species diversity was evaluated by using the Simpson, Shannon
      Weaner, and Pielou indices. Hantavirus antigens or antibodies in lung and blood
      samples of all the captured host animals were detected by direct or indirect
      immunofluorescence. RESULTS: Nine animal species of hantavirus were distributed
      in the forest ecosystem of Jiuhua Mountain. Of these, Niviventer confucianus and
      Apodemus agrarius were predominant, and N. confucianus, Rattus norvegicus, and
      Mus musculus had relatively large niche breadth index values. The host animals in
      the eastern and western mountain regions shared similar biodiversity index
      characteristics, predominant species, and species structures. Hantavirus was
      detected in 5 host animal species in Jiuhua Mountain area, the carriage rate of
      hantavirus was 6.03%. The average density of host animals in forest areas of the
      mountainous area was only 2.20%, and the virus infection rate in the healthy
      population was 2.33%. CONCLUSION: The circulation of hantavirus was low in the
      forest areas of Jiuhua Mountain and did not pose a threat to human health.

PMID- 25374019
TI  - The Prevalence of HIV Drug Resistance among Treatment-failure Individuals and
      Treatment-naive Individuals in China: A Meta-analysis.
AB  - OBJECTIVE: To understand drug resistance prevalence among treatment-failure and
      treatment-naive HIV-positive individuals in China. METHODS: We searched five
      electronic databases (Wanfang, CNKI, CQVIP, SinoMed, and Pubmed) for studies of
      HIV drug resistance. Random-effects models were carried out to estimate the
      prevalence of drug resistance among treatment-failure and treatment-naive
      individuals, respectively. RESULTS: The estimated nationwide rates of HIV drug
      resistance to any-class drugs among treatment-failure and treatment-naive
      individuals were 57% (95% CI: 49%-65%) and 3.23% (95% CI: 2.47%-4.07%),
      respectively. Among the drug classes, the prevalence of resistance to PIs was low
      (1.45%; 95% CI: 0.73%-2.33%) in treatment-failure individuals, although high
      rates of resistance to NNRTIs (54%; 95% CI: 45%-63%) and NRTIs (40%; 95% CI: 32%
      49%) were found. Resistance to any-class drugs, NNRTIs and NRTIs manifested
      regional differences, but resistance to PIs did not. Positive correlations were
      observed between resistance to NNRTIs and NRTIs among treatment-failure and
      treatment-naive individuals, respectively. CONCLUSION: The prevalence of HIV drug
      resistance to NNRTIs and NRTIs among treatment-failure individuals was high. In
      contrast, the prevalence of drug resistance among treatment-naive individuals was
      low. The epidemics of drug resistance matched current treatment strategies and
      interventions in China. Surveillance for HIV drug resistance is necessary to
      assess the sustainability and durability of current treatment regimens.

PMID- 25374020
TI  - Assessment of Exposure to Polybrominated Dipheny Ethers via Inhalation and Diet
      in China.
AB  - OBJECTIVE: This paper is to assess the current status of polybrominated diphenyl
      ethers (PBDEs) contamination in the environment in China and estimate the
      exposure to PBDEs in non-occupational populations. METHODS: A total of 80
      research papers published from January 2001 to October 2013 were selected.
      Geographic information system (GIS) was used in mapping PBDE concentrations and
      distributions in environmental media. Ni's model was applied to calculate ?PBDE
      intake via the intakes of contaminated food, water and air in the Pearl River
      Delta and Yangtze River Delta. RESULTS: BDE-209 was found to be the major PBDE
      congener in the environmental media and food in China. PBDE concentrations varied
      among different areas, among which the contamination in Guangdong Province was
      most serious. Daily intake of ?PBDEs was 225.1-446.0 ng/d for adults in the Pearl
      River Delta, which was higher than the intake for those living in the Yangtze
      River Delta (148.9-369.8 ng/d). CONCLUSION: Atorvastatin can attenuate LPS
      induced TNF-alpha expression and production by activating HO-1 via the ERK and
      p38 MAPK pathways, suggesting that atorvastatin can be used in treatment of
      inflammatory diseases such as sepsis, especially in those with atherosclerotic
      diseases.

PMID- 25374021
TI  - Protein Phosphatase 2C of Toxoplasma Gondii Interacts with Human SSRP1 and
      Negatively Regulates Cell Apoptosis.
AB  - OBJECTIVE: The protozoan Toxoplasma gondii expresses large amounts of a 37 kDa
      Type 2C serine-threonine phosphatase, the so-called TgPP2C which has been
      suggested to contribute to parasite growth regulation. Ectopic expression in
      mammalian cells also indicated that the enzyme could regulate growth and
      survival. In this study, we aimed to investigate the interaction of TgPP2C with
      human SSRP1 (structure-specific recognition protein 1) and the effects of TgPP2C
      on cell viability. METHODS: The yeast two hybrid system, His-tag pull-down and co
      immunoprecipitation assays were used to confirm the interaction of TgPP2C with
      SSRP1 and determine the binding domain on SSRP1. The evaluation of cell apoptosis
      was performed using cleaved caspase-3 antibody and Annexin-V/PI kit combined with
      flow cytometry. RESULTS: We identified human SSRP1 as an interacting partner of
      TgPP2C. The C-terminal region of SSRP1 including the amino acids 471 to 538 was
      specifically mapped as the region responsible for interaction with TgPP2C. The
      overexpression of TgPP2C down-regulated cell apoptosis and negatively regulated
      apoptosis induced by DRB, casein kinase II (CKII) inhibitor, through enhanced
      interaction with SSRP1. CONCLUSION: TgPP2C may be a parasitic factor capable of
      promoting cell survival through interaction with the host protein SSRP1, thereby
      creating a favorable environment for parasite growth.

PMID- 25374022
TI  - Outbreak of dengue Fever in central China, 2013.
AB  - In 2013, the first dengue fever (DF) outbreak in central China was reported in
      the central of Henan province, northern temperate regions, although they have
      been sequentially recorded in Southern China. 106 suspected DF cases were
      reported and 73 patients were confirmed dengue virus type 3 (DEN-3) infections.
      62/392 (15.8%) local health persons showed DEN antibodies positive. To this day
      Henan is the northernmost province in China which has been reported about
      outbreak of DF and what is important is that it warns us the endemic range of DF
      has been expanded geographically in China. 

PMID- 25374023
TI  - Rapid Identification of Bacterial Species Associated with Bronchiectasis via
      Metagenomic Approach.
AB  - Bronchiectasis is a chronic lung disorder and a number of bacterial pathogens are
      involved. However, 30%-40% of sputum and purulent samples in good quality failed
      to grow any pathogenic bacteria, making it difficult to confirm the pathogen. In
      this study, we collected bronchoalveolar lavage fluid from a bronchiectasis
      patient undergoing acute exacerbation, and sent for 16S rDNA pyrosequencing by a
      454 GS Junior machine. Metagenomic analysis showed the composition of bacterial
      community in sample was complex. More than a half of reads (51.3%) were from
      Pseudomonas aeruginosa. This result was corresponding with the culture result but
      came out 2 d earlier, which is meaningful for early diagnosis and treatment. The
      detection with 16S rDNA pyrosequencing technology is more sensitive and rapid
      than routine culture, and can detect the co-infection or symbiosis in airway,
      giving us a novel and convenient approach to perform rapid diagnosis. 

PMID- 25374024
TI  - Curcuminoids Target Decreasing Serum Adipocyte-fatty Acid Binding Protein Levels
      in Their Glucose-lowering Effect in Patients with Type 2 Diabetes.
AB  - Whether supplementation of curcuminoids decreases serum adipocyte-fatty acid
      binding protein (A-FABP) level and whether this decrease benefits glucose control
      is unclear. One-hundred participants (n=50 administered curcuminoids, n=50
      administered placebo) from our previous report on the effect of curcuminoids on
      type 2 diabetes in a 3-month intervention were assessed for levels of serum A
      FABP, oxidative stress, and inflammatory biomarkers. Curcuminoids supplementation
      led to significant decreases in serum A-FABP, C-reactive protein (CRP), tumor
      necrosis factor-alpha, and interleukin-6 levels. Curcuminoids supplementation
      also significantly increased serum superoxide dismutase (SOD) activity. The
      change in serum A-FABP levels showed positive correlations with changes in levels
      of glucose, free fatty acids (FFAs), and CRP in subjects supplemented with
      curcuminoids. Further stepwise regression analysis showed that A-FABP was an
      independent predictor for levels of FFAs, SOD, and CRP. These results suggest
      that curcuminoids may exert anti-diabetic effects, at least in part, by
      reductions in serum A-FABP level. A-FABP reduction is associated with improved
      metabolic parameters in human type 2 diabetes. 

PMID- 25374025
TI  - 90d Exposure to Nonylphenol has Adverse Effects on the Spermatogenesis and Sperm
      Maturation of Adult Male Rats.
AB  - This study was conducted to elucidate the reproductive effect of NP on testis,
      epididymis and epididymal sperm in vivo. Adult male Sprague-Dawley rats were
      gavaged with NP at 0, 40, 100, or 250 mg/kg body weight (bw) on alternate days
      for 90 d. The results showed that oral administration of NP may damage the
      structure and function of testis, induce apoptosis and oxidative stress in
      epididymis or even have cytotoxic effects on epididymal sperm. 

PMID- 25374026
TI  - Methodology and application for health risk classification of chemicals in foods
      based on risk matrix.
AB  - The method has been developed to accurately identify the magnitude of health
      risks and provide scientific evidence for implementation of risk management in
      food safety. It combines two parameters including consequence and likelihood of
      adverse effects based on risk matrix. Score definitions and classification for
      the consequence and the likelihood of adverse effects are proposed. The risk
      score identifies the intersection of consequence and likelihood in risk matrix
      represents its health risk level with different colors: 'low', 'medium', 'high'.
      Its use in an actual case is shown. 

PMID- 25374027
TI  - Respiratory syncytial virus receptor expression in the mouse and viral tropism.
AB  - Human respiratory syncytial virus (RSV) infects airway epithelium and can cause
      serious illnesses such as bronchiolitis and pneumonia. With the discovery of cell
      surface nucleolin as a fusion receptor for RSV, the question arose as to whether
      nucleolin could explain RSV tropism in vivo. Here, we report the distribution of
      cell-surface nucleolin expression in tissues of normal mice and how this
      distribution of expression relates to what is known about RSV tropism and its
      clinical manifestations. Our results show evidence of cell-surface nucleolin
      expression in the respiratory tract. In addition, cell-surface nucleolin is
      expressed in tissues outside of the respiratory tract, many of which correspond
      to previous reports of tissue-specific RSV infection, and others that may allude
      to additional potential sites for RSV infection in vivo. Furthermore, our work
      provides a foundation for the investigation of nucleolin's physiological function
      in various healthy mammalian tissues.

PMID- 25374028
TI  - A review on response of immune system in spinal cord injury and therapeutic
      agents useful in treatment.
AB  - Every year more than 12,000 people in US alone suffer from spinal cord injury.
      However, complete recovery of physical function is difficult due to multiple
      factors involved in disease progression. Currently available therapeutic regimens
      do not address all the factors concerned with the disease progression. The
      present review focuses mainly on the role of immune cells in progression of
      spinal cord injury and the drugs that target these immune cells. Literature
      search shows that inflammatory reactions and subsequent reactions that follow
      direct injury to spinal cord are sometimes responsible for the severity of the
      disease. Therefore, for design of proper treatment regimen a deep understanding
      in this area is required. Understanding the pathophysiology will help in creating
      delivery system that can target multiple factors involved in progression of
      spinal cord injury. A combination of various treatment strategies is required to
      reduce the disability in patients with spinal cord injury. 

PMID- 25374029
TI  - Progress in studies of structure, mechanism and antagonists interaction of GPCR
      co-receptors for HIV.
AB  - Chemokine receptors are G protein-coupled receptors that contain seven trans
      membrane domains. CXCR4 and CCR5 as major co-receptors for HIV-1 entry into host
      cells are implicated in cancer and inflammation. They have been attractive
      targets for the pharmaceutical industry basing on their roles in HIV disease.
      Homology modeling, molecular docking, molecular dynamics, Molecular
      Mechanics/Generalized Born Surface Area and many other computational methods are
      applied to illustrate the structure, function and binding site of GPCR. Moreover,
      the high resolution crystal structures of CXCR4 and CCR5 have provided extremely
      valuable structural information and receptor activation mechanisms, enable
      structure-based drug discovery for the treatment of HIV-1 infection. We also
      describe the recent progress about the small molecule antagonists of CXCR4 and
      CCR5 and the interaction between GPCR and their ligands predicted by molecular
      docking and molecular dynamics methods. Future research questions and further
      investigations are outlined to highlight some researches that may be relevant to
      the advancement of therapies targeting the important receptor related with HIV. 

PMID- 25374030
TI  - An oligodeoxynucleotide with CCT repeats restrains CpG ODN-induced TLR9
      trafficking.
AB  - Toll-like receptor 9 (TLR9) can sense pathogen DNA and CpG ODN or even self-DNA
      by trafficking assisted by Unc93B1, an endoplasmic reticulum (ER) transmembrane
      protein, from ER to endolysosomes or cell surface. In previous study, we found
      that an oligodeoxynucleotide with CCT repeats (SAT05f) could selectively inhibit
      TLR7/9 activation. However, the mechanism for the inhibitory activity of SAT05f
      is still unknown. In present research, it was found that SAT05f could inhibit CpG
      ODN-induced the intracellular trafficking of TLR9 and Unc93B1 with feedback the
      responses of decreased surface TLR9 and enhanced TLR9 mRNA expression but not
      influence TLR9 protein level by using human plasmacytoid dendritic cell line CAL
      1 cells, suggesting that SAT05f inhibits TLR9 activation by restraining TLR9
      trafficking. Since the mitochondrial DNA released from injured tissue can cause
      systemic inflammatory response syndrome (SIRS), this study may provide valuable
      data for prevention and treatment of SIRS and rescue severe trauma patients. 

PMID- 25374031
TI  - Enhancing nucleic acid delivery, insights from the cationic phospholipid
      carriers.
AB  - The development of nucleic acid-based drugs has attracted considerable interest
      in the past two decades as a new category of biologics. A key challenge in
      successfully achieving the full potential of nucleotide therapeutics is their
      efficient delivery. Synthetic cationic lipids are currently the most extensively
      used non-viral nucleotide carriers because of their ability to form complexes
      with the nucleic acids. Here we examine the properties of oligonucleotide
      lipoplexes with a particularly noteworthy cationic lipid class, the cationic
      phosphatidylcholines (PCs) which exhibit low toxicity and good nucleotide
      delivery efficacy. Studies on a set of cationic PCs reveal the existence of a
      strong, systematic dependence of their carrier efficiency on the lipid
      hydrocarbon chain structure. Their activity rises with the increase in chain
      unsaturation and declines with the increase in chain length. Maximum transfection
      is detected for ethyl-PC (ePC) with monounsaturated 14:1 chains. The same lipid
      exhibits maximum activity also in intracellular delivery of siRNA. As the lipid
      phase behavior is known to depend substantially on the hydrocarbon chain
      structure, the above relationships validate a view that cationic PC phase
      properties are an important factor for their activity. Indeed, time-resolved X
      ray diffraction studies showed that the rate of the nucleotide release from the
      lipoplexes, as well as their transfection activity, correlate with the non
      lamellar phase progressions detected in mixtures of cationic PCs with biomembrane
      lipids. These findings emphasize the role of the non-lamellar lipid mesophases in
      the nucleic acid transport across the cellular membranes and their intracellular
      release. 

PMID- 25374032
TI  - G protein-coupled receptor signaling to Kir channels in Xenopus oocytes.
AB  - Kir3 (or GIRK) channels have been known for nearly three decades to be activated
      by direct interactions with the betagamma subunits of heterotrimeric G
      (Galphabetagamma) proteins in a membrane-delimited manner. Galpha also interacts
      with GIRK channels and since PTX-sensitive Galpha subunits show higher affinity
      of interaction they confer signaling specificity to G Protein- Coupled Receptors
      (GPCRs) that normally couple to these G protein subunits. In heterologous
      systems, overexpression of non PTX-sensitive Galpha subunits scavenges the
      available Gbetagamma and biases GIRK activation through GPCRs that couple to
      these Galpha subunits. Moreover, all Kir channels rely on their direct
      interactions with the phospholipid PIP2 to maintain their activity. Thus, signals
      that activate phospholipase C (e.g. through Gq signaling) to hydrolyze PIP2
      result in inhibition of Kir channel activity. In this review, we illustrate with
      experiments performed in Xenopus oocytes that Kir channels can be used
      efficiently as reporters of GPCR function through Gi, Gs or Gq signaling. The
      membrane-delimited nature of this expression system makes it highly efficient for
      constructing dose-response curves yielding highly reproducible apparent
      affinities of different ligands for each GPCR tested. 

PMID- 25374033
TI  - Targeted delivery of tumor suppressor microRNA-1 by transferrin-conjugated
      lipopolyplex nanoparticles to patient-derived glioblastoma stem cells.
AB  - OBJECTIVE: Among heterogeneous glioblastoma multiforme (GBM) cells, glioblastoma
      stem cells (GSCs) is a subpopulation having a critical role in tumor initiation
      and therapy resistance. Thus targeting GSCs would be an essential step to
      completely eradicate this lethal disease. MicroRNA-1 (miR-1) expression is
      deregulated in GBM patients and restoration of miR-1 by viral-vector in GBM cells
      has been demonstrated to inhibit tumor initiation and attenuate cell migration.
      Here, we show that a transferrin-targeting non-invasive nanoparticle delivery
      system (Tf-NP) can efficiently deliver miR-1 to GBM patient-derived GSC-enriched
      sphere cultures (GBM spheres). METHODS: Delivery efficiency of the transferrin-
      targeting non-invasive nanoparticle was investigated by flow cytometry and
      further confirmed by confocal microscopy. The levels of miR-1 and its target
      molecules in GBM spheres were measured by qRT-PCR and immunoblotting. Migration
      capacity of Tf-NP-miR-1 treated GBM spheres were evaluated by transwell migration
      assay. RESULTS: Tf-NPmiR- 1 treatment resulted in an over 200-fold increase of
      mature miR-1 compared to free miR-1 and Tf-NP-miR negative control (Tf-NP-miR
      NC). Transferrin-mediated NP delivery resulted in a 3-fold higher delivery
      efficiency compared to NP without transferrin modification. Tf-NP-miR-1 treatment
      on GBM spheres significantly inhibited migration of GBM spheres by 30-50% with
      associated decline of MET and EGFR expression. Our data supported that Tf-NP
      could be used as an efficient and effective delivery system which has high
      potential to benefit the development of miR-based therapeutics for GBM treatment.

PMID- 25374035
TI  - Large sample size in child and adolescent psychiatric research: the way of
      salvation?

PMID- 25374034
TI  - EEG theta and beta power spectra in adolescents with ADHD versus adolescents with
      ASD + ADHD.
AB  - Attention problems are common in youngsters with attention deficit hyperactivity
      disorder (ADHD) as well as in adolescents with combined autism spectrum disorder
      (ASD) and ADHD. However, it is unknown whether there is psychophysiological
      overlap and/or a difference in electroencephalogram (EEG) power spectra between
      ADHD and comorbid ASD and ADHD (ASD + ADHD), on and off stimulant medication. To
      explore potential differences and overlap, measures of theta and beta power in
      adolescents diagnosed with ADHD (n = 33) versus adolescents with combined ASD +
      ADHD (n = 20), categorized by stimulant medication use (57 % of the total
      sample), were compared. EEG measures were acquired in three conditions: (1)
      resting state, eyes closed (2) resting state, eyes open and (3) during an oddball
      task. In addition, performance on the d2 attention test was analyzed. Adolescents
      with ADHD displayed more absolute theta activity than adolescents with ASD + ADHD
      during the eyes open and task conditions, independent of stimulant medication
      use. In addition, only the adolescents with ADHD showed an association between
      diminished attention test performance and increased theta in the eyes open
      condition. Results of the current study suggest that although there is behavioral
      overlap between ADHD characteristics in adolescents with ADHD and adolescents
      with combined ASD + ADHD, the underlying psychophysiological mechanisms may be
      different. Adolescents with ASD + ADHD exhibited fewer of the EEG physiological
      signs usually associated with ADHD, although there was an overlap in attentional
      problems between the groups. This may indicate that treatments developed for ADHD
      work differently in some adolescents with ASD + ADHD and adolescents with ADHD
      only.

PMID- 25374036
TI  - Perceptions of division directors in general internal medicine about the
      importance of and support for scholarly work done by clinician-educators.
AB  - PURPOSE: To determine perceptions of general internal medicine (GIM) division
      directors of the importance of and support for clinician-educators' (CEs')
      scholarship. METHOD: In 2010, the authors identified 127 accredited U.S. MD
      granting medical schools with a GIM division, identified 144 GIM directors, and
      were able to survey 129 of them. Directors were asked to rate the importance of
      specific CE scholarly accomplishments for promotion from assistant to associate
      professor, to describe current research support for CEs, and to state how they
      would support the scholarly work of CEs if they had funding. RESULTS: Fifty-five
      directors (42.6%) from 52 institutions responded; there were no significant
      differences between responding and nonresponding schools. Curriculum development,
      presentations at national meetings and other institutions, review articles, and
      book chapters were rated as "most/very important" or "important/somewhat
      important" by over 90%. Approximately half rated published original peer-reviewed
      articles as "most/very important"; slightly less than half rated these "not
      important," a difference associated with having a specific CE track. If $100,000
      per year were available to enhance the scholarly productivity of CEs, directors
      suggested spending it on faculty development, project coordination, protected
      time for CEs, and methodological and statistical support. CONCLUSIONS: This
      nationwide survey of GIM division directors confirms that academic CEs in GIM are
      judged on a wide variety of scholarly activities, many of which are consistent
      across institutions. However, academic GIM CEs need to understand their
      institutions' specific criteria, especially regarding the value placed on
      original, peer-reviewed publications.

PMID- 25374037
TI  - A comprehensive information technology system to support physician learning at
      the point of care.
AB  - MayoExpert is a multifaceted information system integrated with the electronic
      medical record (EMR) across Mayo Clinic's multisite health system. It was
      developed as a technology-based solution to manage information, standardize
      clinical practice, and promote and document learning in clinical contexts.
      Features include urgent test result notifications; models illustrating expert
      approved care processes; concise, expert-approved answers to frequently asked
      questions (FAQs); a directory of topic-specific experts; and a portfolio for
      provider licensure and credentialing. The authors evaluate MayoExpert's reach,
      effectiveness, adoption, implementation, and maintenance. Evaluation data sources
      included usage statistics, user surveys, and pilot studies.As of October 2013,
      MayoExpert was available at 94 clinical sites in 12 states and contained 1,368
      clinical topics, answers to 7,640 FAQs, and 92 care process models. In 2012,
      MayoExpert was accessed at least once by 2,578/3,643 (71%) staff physicians,
      900/1,374 (66%) midlevel providers, and 1,728/2,291 (75%) residents and fellows.
      In a 2013 survey of MayoExpert users with 536 respondents, all features were
      highly rated (>=67% favorable). More providers reported using MayoExpert to
      answer questions before/after than during patient visits (68% versus 36%). During
      November 2012 to April 2013, MayoExpert sent 1,660 notifications of new-onset
      atrial fibrillation and 1,590 notifications of prolonged QT. MayoExpert has
      become part of routine clinical and educational operations, and its care process
      models now define Mayo Clinic best practices. MayoExpert's infrastructure and
      content will continue to expand with improved templates and content organization,
      new care process models, additional notifications, better EMR integration, and
      improved support for credentialing activities.

PMID- 25374038
TI  - Seasonal variation in family member perceptions of physician competence in the
      intensive care unit: findings from one academic medical center.
AB  - PURPOSE: Researchers have found mixed results about the risk to patient safety in
      July, when newly minted physicians enter U.S. hospitals to begin their clinical
      training, the so-called "July effect." However, patient and family satisfaction
      and perception of physician competence during summer months remain unknown.
      METHOD: The authors conducted a retrospective observational cohort study of 815
      family members of adult intensive care unit (ICU) patients who completed the
      Family Satisfaction with Care in the Intensive Care Unit instrument from eight
      ICUs at Beth Israel Deaconess Medical Center, Boston, Massachusetts, between
      April 2008 and June 2011. The association of ICU care in the summer months (July
      September) versus other seasons and family perception of physician competence was
      examined in univariable and multivariable analyses. RESULTS: A greater proportion
      of family members described physicians as competent in summer months as compared
      with winter months (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.2-3.0; P
      = .003). After adjustment for patient and proxy demographics, severity of
      illness, comorbidities, and features of the admission in a multivariable model,
      seasonal variation of family perception of physician competence persisted (summer
      versus winter, OR of judging physicians competent 2.4; 95% CI 1.3-4.4; P = .004).
      CONCLUSIONS: Seasonal variation exists in family perception of physician
      competence in the ICU, but opposite to the "July effect." The reasons for this
      variation are not well understood. Further research is necessary to explore the
      role of senior provider involvement, trainee factors, system factors such as
      handoffs, or other possible contributors.

PMID- 25374039
TI  - The effect of an intervention to break the gender bias habit for faculty at one
      institution: a cluster randomized, controlled trial.
AB  - PURPOSE: Despite sincere commitment to egalitarian, meritocratic principles,
      subtle gender bias persists, constraining women's opportunities for academic
      advancement. The authors implemented a pair-matched, single-blind, cluster
      randomized, controlled study of a gender-bias-habit-changing intervention at a
      large public university. METHOD: Participants were faculty in 92 departments or
      divisions at the University of Wisconsin-Madison. Between September 2010 and
      March 2012, experimental departments were offered a gender-bias-habit-changing
      intervention as a 2.5-hour workshop. Surveys measured gender bias awareness;
      motivation, self-efficacy, and outcome expectations to reduce bias; and gender
      equity action. A timed word categorization task measured implicit
      gender/leadership bias. Faculty completed a work-life survey before and after all
      experimental departments received the intervention. Control departments were
      offered workshops after data were collected. RESULTS: Linear mixed-effects models
      showed significantly greater changes post intervention for faculty in
      experimental versus control departments on several outcome measures, including
      self-efficacy to engage in gender-equity-promoting behaviors (P = .013). When >=
      25% of a department's faculty attended the workshop (26 of 46 departments),
      significant increases in self-reported action to promote gender equity occurred
      at three months (P = .007). Post intervention, faculty in experimental
      departments expressed greater perceptions of fit (P = .024), valuing of their
      research (P = .019), and comfort in raising personal and professional conflicts
      (P = .025). CONCLUSIONS: An intervention that facilitates intentional behavioral
      change can help faculty break the gender bias habit and change department climate
      in ways that should support the career advancement of women in academic medicine,
      science, and engineering.

PMID- 25374040
TI  - Blink or think: can further reflection improve initial diagnostic impressions?
AB  - PURPOSE: Experienced clinicians derive many diagnoses intuitively, because most
      new problems they see closely resemble problems they've seen before. The majority
      of these diagnoses, but not all, will be correct. This study determined whether
      further reflection regarding initial diagnoses improves diagnostic accuracy
      during a high-stakes board exam, a model for studying clinical decision making.
      METHOD: Keystroke response data were used from 500 residents who took the 2010
      American Board of Internal Medicine (ABIM) Internal Medicine Certification
      Examination. Data included time to initial response on each question, whether the
      answer was correct, and whether or not the resident changed her or his initial
      response. The focus was on 80 diagnosis questions that comprised realistic
      clinical vignettes with multiple-choice single-best answers. Cognitive skill
      (ability) was measured using overall exam scores. Case complexity was determined
      using item difficulty (proportion of examinees that correctly answered the
      question). A hierarchical generalized linear model was used to assess the
      relationship between time spent on initial responses and the probability of
      correctly answering the questions. RESULTS: On average, residents changed their
      responses on 12% of all diagnosis questions (or 9.6 questions out of 80).
      Changing an answer from incorrect to correct was almost twice as likely as
      changing an answer from correct to incorrect. The relationship between response
      time and accuracy was complex. CONCLUSIONS: Further reflection appears to be
      beneficial to diagnostic accuracy, especially for more complex cases.

PMID- 25374041
TI  - Linking simulation-based educational assessments and patient-related outcomes: a
      systematic review and meta-analysis.
AB  - PURPOSE: To examine the evidence supporting the use of simulation-based
      assessments as surrogates for patient-related outcomes assessed in the workplace.
      METHOD: The authors systematically searched MEDLINE, EMBASE, Scopus, and key
      journals through February 26, 2013. They included original studies that assessed
      health professionals and trainees using simulation and then linked those scores
      with patient-related outcomes assessed in the workplace. Two reviewers
      independently extracted information on participants, tasks, validity evidence,
      study quality, patient-related and simulation-based outcomes, and magnitude of
      correlation. All correlations were pooled using random-effects meta-analysis.
      RESULTS: Of 11,628 potentially relevant articles, the 33 included studies
      enrolled 1,203 participants, including postgraduate physicians (n = 24 studies),
      practicing physicians (n = 8), medical students (n = 6), dentists (n = 2), and
      nurses (n = 1). The pooled correlation for provider behaviors was 0.51 (95%
      confidence interval [CI], 0.38 to 0.62; n = 27 studies); for time behaviors, 0.44
      (95% CI, 0.15 to 0.66; n = 7); and for patient outcomes, 0.24 (95% CI, -0.02 to
      0.47; n = 5). Most reported validity evidence was favorable, though studies often
      included only correlational evidence. Validity evidence of internal structure (n
      = 13 studies), content (n = 12), response process (n = 2), and consequences (n =
      1) were reported less often. Three tools showed large pooled correlations and
      favorable (albeit incomplete) validity evidence. CONCLUSIONS: Simulation-based
      assessments often correlate positively with patient-related outcomes. Although
      these surrogates are imperfect, tools with established validity evidence may
      replace workplace-based assessments for evaluating select procedural skills.

PMID- 25374042
TI  - Evaluation of the pharmacokinetics and safety of a single oral dose of fasiglifam
      in subjects with normal or varying degrees of impaired renal function.
AB  - INTRODUCTION: Approximately one-third of patients with type 2 diabetes mellitus
      (T2DM) have concurrent renal impairment. There are limited therapeutic options
      for these patients. Fasiglifam is a G protein-coupled receptor 40 agonist that
      was under investigation for the treatment of T2DM. The objective of this study
      was to evaluate the potential effect of renal impairment on the pharmacokinetics
      and safety of a single dose of fasiglifam and its metabolite M-1. METHODS: This
      was a phase I, open-label, parallel-group study. Subjects with varying degrees of
      renal function received a single oral dose of fasiglifam 50 mg. Blood and urine
      samples were collected through 168 h postdose. Study endpoints were
      pharmacokinetic and safety variables. RESULTS: Fifty-three subjects were
      enrolled. Mean fasiglifam plasma concentrations were higher in subjects with mild
      renal impairment compared with other groups, but within each renal function
      cohort, plasma concentrations tended to decrease with decreasing renal function.
      Regression analyses indicated that fasiglifam exposure decreased and M-1 exposure
      increased with decreasing renal function. Predicted exposure values at about the
      midpoint of creatinine clearance for each renal impairment group differed by up
      to 21% (fasiglifam) and 87% (M-1) from that of the normal renal function group.
      Hemodialysis had no effect on fasiglifam or M-1 exposure. Fasiglifam renal
      clearance (CLR) was not affected, but M-1 CLR decreased with increasing
      impairment. No incidences of hypoglycemia were reported during the study.
      CONCLUSION: Varying renal function status did not have a significant impact on
      the clearance of fasiglifam in this study.

PMID- 25374043
TI  - The importance, measurement and practical implications of worker's expectations
      for return to work.
AB  - PURPOSE: Workers' own expectations for return to work consistently predict work
      status. To advance the understanding of the relationship between RTW expectations
      and outcomes, we reviewed existing measures to determine those which we felt were
      the most likely to capture the construct. METHOD: A comprehensive search of the
      work-disability rehabilitation literature was undertaken. The review of the
      measures was conducted in three steps: first, a review of terminology; second, an
      examination of whether a time reference was included; third, an evaluation of
      ease of comprehension, and applicability across contexts. RESULTS: A total of 42
      different measures were identified. One of the most striking findings was the
      inconsistency in terminology. Measures were also limited by not including a time
      reference. Problems were also identified with regards to ease of understanding,
      utility of response options, and applicability in a wide variety of research and
      applied settings. CONCLUSIONS: Most previously used measures contain elements
      that potentially limit utility. However, it would seem that further development
      can overcome these, resulting in a tool that provides risk prediction
      information, and an opportunity to start a conversation to help identify problems
      that might negatively impact a worker's movement through the RTW process and the
      outcomes achieved. Implications for Rehabilitation Return to work is an integral
      part of workplace injury management. The capture of RTW expectations affords a
      way to identify the potential for less than optimal RTW processes and outcomes. A
      mismatch between an injured worker's expectations and what other stakeholders
      might expect suggests that efforts could be made to determine what is causing the
      injured worker's concerns. Once underling issues are identified, work can be put
      into resolving these so that the worker's return to the workplace is not impeded.

PMID- 25374044
TI  - How is physical activity monitored in people following stroke?
AB  - PURPOSE: To describe how physical activity is monitored following stroke; to
      summarise methods and devices used across the stroke pathway and document their
      psychometric properties. METHODS: Searches of five databases identified studies
      that included stroke survivors whose physical activity was quantitatively
      measured. Two reviewers independently determined inclusion. A descriptive
      synthesis was undertaken and reliability data for specific methods of monitoring
      physical activity were pooled where possible. RESULTS: Ninety-one papers (60
      using devices and 31 using observational methods) met inclusion criteria, with
      3479 participants aged 21-96 years. Twenty-nine devices (72% accelerometers) were
      identified. Devices were typically used to measure ambulant participants more
      than 6 months following stroke. Direct observation of physical activity was
      commonly used for inpatients. No outcome measurements were common to all
      methods/devices. Test-retest reliability was not reported for 23 devices; for the
      remaining six it ranged from r = 0.44 to r = 0.99. Inter-rater reliability of
      observational methods ranged from 0.51 to 1.0. Validity was infrequently
      reported. CONCLUSIONS: Physical activity outcomes were variable. Devices allow
      for unobtrusive, sustained monitoring in free-living environments. Observational
      methods suit inpatient settings but are time and labour intensive. No single
      approach appears superior but standardisation of outcomes would improve the
      field. IMPLICATIONS FOR REHABILITATION: Physical activity measurement is highly
      variable following stroke and better definition of physical activity outcomes
      would enhance the field. Accelerometry and behavioural mapping are most commonly
      used to measure physical activity following stroke, each have advantages and
      disadvantages depending on the setting and the outcome of interest. There is no
      single device ideal for clinical application for people following stroke.

PMID- 25374045
TI  - Executive dysfunction post-stroke: an insight into the perspectives of
      physiotherapists.
AB  - PURPOSE: To gain an understanding of physiotherapy practice in relation to
      executive dysfunction (ED) post-stroke. METHOD: Three focus groups were conducted
      using semi-structured interview schedules to highlight how ED post-stroke was
      understood by 12 physiotherapists with greater than 1 year of experience working
      in the area of stroke care. The focus group data were analysed using qualitative
      data analysis. RESULTS: The themes extracted from the data on physiotherapists'
      self-reported knowledge of ED post-stroke were: physiotherapists' lack of
      knowledge of ED post-stroke; current physiotherapy practice regarding ED post
      stroke; the negative impact of ED on physiotherapy rehabilitation post-stroke and
      the future learning needs of physiotherapists regarding ED post-stroke.
      CONCLUSIONS: Current results demonstrate that ED has negative implications for
      physiotherapy rehabilitation post-stroke. Although further interdisciplinary
      research is warranted, the present results suggest that physiotherapists should
      be aware of the presence of ED in people post-stroke and develop strategies to
      minimise the impact of ED on physiotherapy rehabilitation. Implications for
      Rehabilitation Physiotherapists report a lack of knowledge of ED post-stroke and
      a requirement for future learning and training regarding the optimal management
      of people with ED undergoing physiotherapy rehabilitation post-stroke. ED has
      negative implications for physiotherapy rehabilitation post-stroke and
      physiotherapists should be aware of the presence of ED in people post-stroke and
      develop strategies to minimise the impact of ED on physiotherapy rehabilitation.

PMID- 25374046
TI  - High renal resistive index in hypertensive patients is also associated with serum
      homocysteine level.
AB  - BACKGROUND: Hypertension, homocysteine and renal resistive index are associated
      with atherosclerosis and lead to cardiovascular diseases. In this study, we aimed
      to investigate the association between homocysteine and renal resistive index in
      patients with newly diagnosed hypertension. METHODS: A total of 221 subjects were
      included in this case-control study. The study group consisted of 116
      hypertensive patients and the control group consisted of 105 healthy subjects.
      Renal resistive index, homocysteine levels, insulin concentrations and blood
      pressures were measured. RESULTS: Renal resistive index, serum homocysteine
      levels and insulin concentrations were higher in hypertensive patients (p =
      0.006, p < 0.001, respectively). Serum homocysteine levels were associated with
      hypertension (OR 9.5, Cl 95 % 4.86-18.7, p < 0.001). Homocysteine and insulin
      levels were positively correlated with renal resistive index (r = 0.372, p =
      0.001; r = 0.392, p < 0.001, respectively). CONCLUSION: High renal resistive
      index in hypertensive patients is associated with homocysteine.

PMID- 25374047
TI  - The effects of HIV testing advocacy messages on test acceptance: a randomized
      clinical trial.
AB  - BACKGROUND: Nearly 1 in 5 people living with HIV in the United States are unaware
      they are infected. Therefore, it is important to develop and evaluate health
      communication messages that clinicians can use to encourage HIV testing. METHODS:
      The objective was to evaluate health communication messages designed to increase
      HIV testing rates among women and evaluate possible moderators of message effect.
      We used a randomized four-arm clinical trial conducted at urban community
      outpatient health clinics involving 1,919 female patients, 18 to 64 years old.
      The four health message intervention groups were: i) information-only control;
      ii) one-sided message describing the advantages of HIV testing; iii) two-sided
      message acknowledging a superficial objection to testing (i.e., a 20 minute wait
      for results) followed by a description of the advantages of testing; and iv) two
      sided message acknowledging a serious objection (i.e., fear of testing positive
      for HIV) followed by a description of the advantages of testing. The main outcome
      was acceptance of an oral rapid HIV test. RESULTS: Participants were randomized
      to receive the control message (n = 483), one-sided message (n = 480), two-sided
      message with a superficial objection (n = 481), or two-sided message with a
      serious objection (n = 475). The overall rate of HIV test acceptance was 83%. The
      two-sided message groups were not significantly different from the controls. The
      one-sided message group, however, had a lower rate of testing (80%) than the
      controls (86%) (OR, 0.66; 95% CI, 0.47-0.93; P = 0.018). "Perceived obstacles to
      HIV testing" moderated this effect, indicating that the decrease in HIV test
      acceptance for the one-sided message group was only statistically significant for
      those who had reported high levels of obstacles to HIV testing (OR, 0.36; 95% CI,
      0.19-0.67; P = 0.001). CONCLUSIONS: None of the messages increased test
      acceptance. The one-sided message decreased acceptance and this effect was
      particularly true for women with greater perceived obstacles to testing, the very
      group one would most want to persuade. This finding suggests that efforts to
      persuade those who are reluctant to get tested, in some circumstances, may have
      unanticipated negative effects. Other approaches to messaging around HIV testing
      should be investigated, particularly with diverse, behaviorally high-risk
      populations. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00771537.
      Registration date: October 10. 2008.

PMID- 25374048
TI  - Long-term outcome of liver transplantation in HCV/HIV coinfected haemophilia
      patients. A single centre study of 10 patients.
AB  - The outcome and clinical features during long term follow-up of 10 haemophilia
      patients (haemophilia A n = 9, haemophilia B n = 1), who underwent successful
      orthotopic liver transplantation (OLT) due to hepatitis associated liver disease,
      are summarised. PATIENTS: Eight patients were HIV/HCV co-infected. Despite severe
      postoperative complications, which were not bleeding-associated, all patients
      survived OLT. RESULTS: Long-term survival was 70% after in mean 8 years follow
      up. Twelve years after OLT one patient developed a cyclosporine-induced
      nephropathy requiring haemodialysis. HIV-HAART was initiated in all patients
      after OLT, and allowed a successful HCV treatment in 6 patients. Factor VIII
      production was sufficient in mean 72 h after OLT and remained stable at subnormal
      to normal FVIII levels of in median 30% (range 14-96%) also during long-term
      follow-up. Post-OLT spontaneous bleeding events were rare compared to pre-OLT,
      therefore, the performance status improved in all patients. DISCUSSION: OLT
      substitutes the hepatic FVIII but has no effect on the extra-hepatic endothelial
      FVIII production, suggesting that in case of severe tissue injury enhanced
      bleeding might occur. Additionally, after OLT there is no acute phase reaction of
      the FVIII protein. Therefore, our OLT patients received in case of a reduced
      FVIII activity a peri-interventional prophylactic short-term FVIII substitution
      in surgical and diagnostic interventions with high bleeding risk. CONCLUSION:
      Bleeding and wound healing disturbances were not seen.

PMID- 25374049
TI  - Synthetic DAF-12 modulators with potential use in controlling the nematode life
      cycle.
AB  - Dafachronic acids (DAs) are 3-keto cholestenoic acids bearing a carboxylic acid
      moiety at the end of the steroid side chain. These compounds interact with the
      DAF-12 receptor, a ligand-dependent transcription factor that acts as a molecular
      switch mediating the choice between arrest at diapause or progression to
      reproductive development and adult lifespan in different nematodes. Recently, we
      reported that the 27-nor-Delta4-DA was able to directly activate DAF-12 in a
      transactivation cell-based luciferase assay and rescued the Mig phenotype of daf
      9(rh50) Caenorhabditis elegans mutants. In the present paper, to investigate
      further the relationship between the structure of the steroid side chain and DAF
      12 activity, we evaluated the in vitro and in vivo activity of Delta4-DA
      analogues with modified side chains using transactivation cell-based assays and
      daf-9(dh6) C. elegans mutants. Our results revealed that introduction of a 24,25
      double bond on the cholestenoic acid side chain did not affect DAF-12 activity,
      whereas shortening the side chain lowered the activity. Most interestingly, the
      C24 alcohol 24-hydroxy-4-cholen-3-one (6) was an antagonist of the DAF-12
      receptor both in vitro and in vivo.

PMID- 25374050
TI  - High lithium anodic performance of highly nitrogen-doped porous carbon prepared
      from a metal-organic framework.
AB  - Theoretical and experimental results have revealed that the lithium-ion storage
      capacity for nitrogen-doped graphene largely depends on the nitrogen-doping
      level. However, most nitrogen-doped carbon materials used for lithium-ion
      batteries are reported to have a nitrogen content of approximately 10 wt% because
      a higher number of nitrogen atoms in the two-dimensional honeycomb lattice can
      result in structural instability. Here we report nitrogen-doped graphene particle
      analogues with a nitrogen content of up to 17.72 wt% that are prepared by the
      pyrolysis of a nitrogen-containing zeolitic imidazolate framework at 800  degrees
      C under a nitrogen atmosphere. As an anode material for lithium-ion batteries,
      these particles retain a capacity of 2,132 mA h g(-1) after 50 cycles at a
      current density of 100 mA g(-1), and 785 mAh g(-1) after 1,000 cycles at 5 A g(
      1). The remarkable performance results from the graphene analogous particles
      doped with nitrogen within the hexagonal lattice and edges. 

PMID- 25374051
TI  - A recurrent deletion mutation in OPA1 causes autosomal dominant optic atrophy in
      a Chinese family.
AB  - Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary
      optic neuropathy and occurs due to the degeneration of the retinal ganglion
      cells. To identify the genetic defect in a family with putative ADOA, we
      performed capture next generation sequencing (CNGS) to screen known retinal
      disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy
      1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation
      (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1
      from the patient skin fibroblasts and found there is six-nucleotide deletion
      (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1
      mRNA and its protein expression have no obvious difference between patient skin
      fibroblast and control. The analysis of protein structure by molecular modeling
      suggests that the mutation may change the structure of OPA1 by formation of an
      alpha helix protruding into an existing pocket. Taken together, we identified an
      OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also
      showed that this mutation affects the structural intactness of OPA1. It provides
      molecular insights for clinical genetic diagnosis and treatment of optic atrophy.

PMID- 25374052
TI  - Comparison of efficacy of three surgical methods of conjunctival autograft
      fixation in the treatment of pterygium.
AB  - Our aim primarily was to compare the recurrence rate with three techniques of
      conjunctival fixation (suture versus fibrin glue versus autologous in situ blood
      coagulum) over bare sclera following pterygium excision. Ninety eyes of 90
      patients with primary pterygium were randomly divided into three groups: group I
      (30 eyes) underwent autografting and fixation with 8-0 vicryl sutures, group II
      (30 eyes) with fibrin glue and group III (30 eyes) with autologous in situ blood
      coagulum. The patients were reviewed on 2nd day, weeks 1 and 4, and at every 3
      months till 12 months after surgery. Rate of recurrence was similar (p = 0.585)
      across the three groups. Time taken for surgery for Group 1 was more as compared
      to group 2 (p < 0.001) and group 3 (p < 0.001). Also, group 2 cases took
      significantly more time as compared to group 3 (p < 0.001). Postoperative patient
      discomfort (foreign body sensation, epiphora, pain and irritation) was more in
      suture-assisted autografting as compared to the other two groups. However, at
      some points along the time line, patient discomfort was significantly more in
      group III as compared to group II. Complications like graft retraction, graft
      displacement and cyst formation were seen in a few patients but were not
      statistically significant across the three groups. All three techniques were
      found to be useful methods and were associated with similar rate of recurrence.

PMID- 25374053
TI  - Synthesis and antifungal activity of 1,2,3-triazole phenylhydrazone derivatives.
AB  - A series of 1,2,3-triazole phenylhydrazone derivatives were designed and
      synthesized as antifungal agents. Their structures were determined based on (1)H
      NMR spectroscopy, MS, elemental analysis and X-ray single-crystal diffraction.
      The antifungal activities were evaluated against four phytopathogenic fungi
      including Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and
      Phytophthora capsici, by the mycelium growth inhibition method in vitro. Compound
      5p exhibited significant anti-phytopathogenic activity, with the EC50 values of
      0.18, 2.28, 1.01, and 1.85 MUg mL(-1), respectively. In vivo testing demonstrated
      that 5p was effective in the control of rice sheath blight, rape sclerotinia rot
      and fusarium head blight. A 3D-QSAR model was built for a systematic SAR profile
      to explore more potent 1,2,3-triazole phenylhydrazone analogs as novel
      fungicides. 

PMID- 25374054
TI  - A visual sensor array for pattern recognition analysis of proteins using novel
      blue-emitting fluorescent gold nanoclusters.
AB  - This paper describes a visual sensor array for pattern recognition analysis of
      proteins based on two different optical signal changes: colorimetric and
      fluorometric, by using two types of novel blue-emitting collagen protected gold
      nanoclusters and macerozyme R-10 protected gold nanoclusters with lower synthetic
      demands. Eight proteins have been well-discriminated by this visual sensor array,
      and protein mixtures after one-dimensional polyacrylamide gel electrophoresis
      also could be well-discriminated. The possible mechanism of this sensor array was
      illustrated and validated by fluorescence spectra, X-ray photoelectron
      spectroscopy (XPS), fluorescence lifetime, isothermal titration calorimetry
      (ITC), and matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry (MALDI-TOF MS) experiments. It was attributed to that the adsorption
      of proteins onto the surface of gold nanoclusters (Au NCs), forming the protein
      Au NCs complex. Furthermore, serums from normal and hepatoma patients were also
      effectively discriminated by this visual sensor array, showing feasible potential
      for diagnostic applications. 

PMID- 25374057
TI  - Is nonoperative treatment of pediatric type I open fractures safe and effective?
AB  - PURPOSE: There is limited literature on nonoperative treatment of open type I
      pediatric fractures. Our purpose was to evaluate the rate of infection in
      pediatric patients with type I open fractures treated nonoperatively at our
      institution without admission from the emergency department (ED). METHODS: We
      performed a retrospective chart review of all patients who sustained a type I
      open fracture of the forearm or tibia from 2000 through 2013. Forty patients fit
      the inclusion criteria: <18 years old with type I open fracture treated
      nonoperatively with irrigation and debridement, followed by closed reduction and
      casting of the fracture under conscious sedation in the ED. All patients were
      discharged home. The primary outcome was presence of infection. Secondary
      outcomes included occurrence of a delayed union, time to union, complications,
      and residual angulation. RESULTS: There were no reported or documented
      infections. There was one case of a retained foreign body (<1 cm) in a mid
      diaphyseal forearm fracture, which was removed in clinic at 4 weeks after the
      patient developed a granuloma with no infectious sequela. There was one case of a
      delayed union; all patients eventually had complete bony union. There was minimal
      residual angulation in both upper and lower extremities at last follow-up.
      CONCLUSIONS: Nonoperative treatment of type I open fractures in pediatric
      patients can be performed safely with little risk of infection. This preliminary
      evidence may serve as a foundation for future prospective studies.

PMID- 25374055
TI  - Design of the INHIBIT trial: preventing inhibitors by avoiding 'danger',
      prolonging half-life and promoting tolerance.
AB  - Inhibitor formation is among the most serious complications of hemophilia
      treatment. With the US FDA licensure of the novel long-lasting recombinant factor
      VIII (FVIII) Fc fusion protein, Eloctate, which prolongs FVIII half-life, we
      propose an innovative approach to prevent inhibitor formation. In this paper, we
      describe a multicenter, Phase II, single-arm, 48-week trial, the INHIBIT trial,
      to determine if Eloctate, begun before a bleed and continued as once weekly
      prophylaxis, will reduce inhibitor formation in children with hemophilia A. We
      hypothesize that avoiding 'danger,' that is, immune activation by a bleed at
      first factor exposure and prolonging FVIII half-life will prevent inhibitors and
      promote FVIII-specific T-cell tolerance. If successful, this approach will
      suggest a new paradigm in clinical practice. 

PMID- 25374058
TI  - Selective ultrasound screening is inadequate to identify patients who present
      with symptomatic adult acetabular dysplasia.
AB  - PURPOSE: One goal of neonatal screening for developmental dysplasia of the hip
      (DDH) is the prevention of late surgery. However, the majority of patients with
      acetabular dysplasia at skeletal maturity are not diagnosed with DDH during
      infancy. Selective ultrasound screening may identify patients with neonatal hip
      instability, but may be ineffective for the prevention of dysplasia presenting in
      adulthood. The purpose of this study is to identify the prevalence of risk
      factors for DDH that would have warranted selective ultrasound screening in
      patients with symptomatic acetabular dysplasia after skeletal maturity. METHODS:
      A prospective hip specialty center registry was used to identify 68 consecutive
      skeletally mature patients undergoing corrective osteotomy for symptomatic
      acetabular dysplasia. Risk factors for DDH evaluated in all patients included
      sex, family history of hip osteoarthritis or DDH, breech, method of delivery,
      previous hip treatments, and birth order. Radiographs [lateral center edge angle
      (CEA), anterior CEA, Tonnis grade, and Tonnis angle] were measured
      preoperatively. RESULTS: Sixty-seven females and one male were identified. No
      patients were previously diagnosed with DDH or received treatment for their hips.
      The majority of patients (85.3 %) did not meet selective ultrasound screening
      guidelines following a stable neonatal hip exam and, therefore, would not have
      been screened in a selective screening program. Of the findings outside of
      screening guidelines, 98.5 % were females, 52.9 % were first born, and 36.8 % had
      a family history of hip osteoarthritis. CONCLUSIONS: The majority (85.3 %) of
      patients with symptomatic acetabular dysplasia at skeletal maturity would not
      have met current recommendations for selective ultrasound screening in the USA
      had they been born today.

PMID- 25374059
TI  - Association between endothelial nitric oxide synthase 894G>T polymorphism and
      prostate cancer risk: a meta-analysis of literature studies.
AB  - To date, several studies have been conducted to assess the association between
      endothelial nitric oxide synthase (eNOS) gene 894G > T polymorphism and prostate
      cancer (PCa) risk, but the results are conflicting. To derive a more precise
      estimation of the relationship between 894G > T polymorphism and PCa risk, the
      present meta-analysis was performed. A total of eight case-control studies were
      included in this meta-analysis. The pooled odds ratio (OR) with 95 % confidence
      interval (CI) was calculated to evaluate the associations. Our results suggested
      that 894G > T polymorphism is associated with PCa risk under codominant (GT vs.
      GG) (OR = 1.11, 95 % CI = 1.01-1.22, P = 0.04) and overdominant (GT vs. GG + TT)
      (OR = 1.12, 95 % CI = 1.02-1.23, P = 0.02) models in the overall population,
      while there are no associations observed under dominant (GT + TT vs. GG),
      recessive (TT vs. GG + GT), and allelic (T vs. G) models. Moreover, when the
      eligible studies were stratified according to sources of control, significant
      association between 894G > T polymorphism and susceptibility of PCa was also
      identified under codominant (OR = 1.12, 95 % CI = 1.01-1.24, P = 0.03) and
      overdominant (OR = 1.13, 95 % CI = 1.02-1.25, P = 0.02) models when using healthy
      individuals as control. However, there are no significant associations found
      under any genetic models when using BPH patients as control group. In conclusion,
      the present meta-analysis suggested that the eNOS gene 894G > T polymorphism
      might be a risk factor in the onset of PCa. 

PMID- 25374060
TI  - Downregulation of CPE regulates cell proliferation and chemosensitivity in
      pancreatic cancer.
AB  - Pancreatic cancer (PC) is one of the most common cancers worldwide and a leading
      cause of cancer-related death. Discovering novel targets is a key for its
      therapy. Carboxypeptidase E (CPE), a subtype of the pro-protein convertases, has
      been shown to be upregulated in many types of cancer, yet its function in PC
      remains elusive. The expressions of CPE in PC cell lines and cancer patients were
      investigated by Western blot and qRT-PCR. In PC cell line BX-pc-3, CPE was
      downregulated and its effect on cancer cell proliferation, migration, cisplatin
      chemosensitivity, and in vivo tumor growth was analyzed by Western blot,
      proliferation assay, invasion assay, and in vivo transplantation, respectively.
      The expression of nuclear factor-kappaB (NF-kappaB), a possible downstream target
      of CPE was examined by Western blot upon CPE regulation in PC cells, and the
      effects of inhibiting NF-kappaB on PC cell invasion and proliferation were
      examined. CPE was significantly upregulated in PC cell lines and tumor tissues.
      Proliferation and invasion assays indicated that downregulation of CPE inhibited
      cancer cell growth and migration and increased chemosensitivity to cisplatin.
      Inoculation of small interfering RNA (siRNA) transfected BX-pc-3 cells into null
      mice demonstrated that downregulation of CPE prevented tumor growth in vivo. NF
      kappaB was directly regulated by CPE in pancreatic cancer, and siRNA-mediated
      inhibition of NF-kappaB exerted similar anti-tumor effect as downregulating CPE.
      Taken together, our results demonstrate that CPE plays an important role in
      pancreatic cancer. Inhibition of CPE may serve as a potential target for PC
      therapeutics. 

PMID- 25374061
TI  - Overexpression of miR-218 inhibits hepatocellular carcinoma cell growth through
      RET.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with
      poor prognosis. Here, we investigated the role of microRNA 218 (miR-218) in
      regulating human HCC development. Quantitative PCR (qPCR) was used to compare the
      expression levels of miR-218 between eight HCC and a normal liver cell lines, as
      well as nine primary HCC tissues and adjacent non-carcinoma tissues. HCC cell
      lines MHCC97L and Huh7 were transfected with lentiviral vector of miR-218 mimics.
      The effect of miR-218 overexpression on cancer cell growth, both in vitro and in
      vivo, as well as cancer cell invasion was examined. A bioinformatic method was
      used to predict the binding of miR-218 to RET proto-oncogene (RET). Small
      interfering RNA (SiRNA)-mediated genetic knock-down of RET was performed in
      MHCC97L and Huh7 cells, and its modulatory effect on miR-218-mediated HCC
      development was examined. miR-218 was found to be downregulated in HCC cell lines
      and primary HCC tissues. Overexpression of miR-218 in MHCC97L or Huh7 cells
      resulted in significant decrease in cell proliferation and invasion capability.
      Overexpression of miR-218 also reduced the tumor growth of xenografted Huh7 cells
      in vivo. The expression of endogenous RET was found to be upregulated by miR-218,
      and siRNA-induced RET downregulation resulted in phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN) upregulation and reversal of the inhibitory
      effect of miR-218 upregulation on HCC proliferation. Our results indicate that
      miR-218 modulates HCC development, and this effect may be through RET and PTEN. 

PMID- 25374062
TI  - The prognostic role of baseline CEA and CA 19-9 values and their time-dependent
      variations in advanced colorectal cancer patients submitted to first-line
      therapy.
AB  - Serum marker evaluation is an easily available prognostic indicator that may help
      clinicians to discriminate patients with an aggressive disease; there are few and
      small-sized studies exploring the prognostic role of baseline carcinoembryonic
      antigen (CEA) values and their variations during first-line therapy, and even
      fewer data are available for carbohydrate antigen 19-9 (CA 19-9). Our aim was to
      analyze the role of those prognostic markers to exploit them in daily clinical
      practice. Data of 892 patients with marker determination before and 3 and/or 6
      months during therapy were extracted from two institutional databases. Patients
      were grouped according to single marker variation as always negative (G0),
      decreasing (G1), stable (G2), or increasing (G3). We evaluated the progression
      free survival (PFS) and the overall survival (OS) of all the patents and
      correlated them with CEA and CA 19-9 values. A concordance between response to
      therapy and marker decrease was evident in 50.2% and in 34.4% of the patients for
      CEA and CA 19-9. Patients with low CEA or CA 19-9 baseline values had a longer
      PFS (15.1 vs. 10.5; 13.6 vs. 10.2 months) and OS (32.0 vs. 22.3; 30.5 vs. 20.1
      months). The same results of PFS and OS were obtained by analyzing the data of
      the four different groups. Multivariate analyses confirmed the independent
      prognostic role of CEA and CA 19-9. Baseline CEA and CA 19-9 levels and their
      kinetics demonstrated to be independent prognostic factors. CA 19-9 dosage is not
      recommended; a possible role of CA 19-9 in patients with negative CEA could be
      worth further evaluation.

PMID- 25374063
TI  - DNA repair gene polymorphisms and clinical outcome of patients with primary small
      cell carcinoma of the esophagus.
AB  - Polymorphisms in DNA repair genes impact on the synthesis of DNA repair proteins
      that are crucial to the repair of DNA damages induced by chemotherapy and
      radiotherapy. We retrospectively examined whether there was an association
      between the selected six single nucleotide polymorphisms (SNPs) of five DNA
      repair genes (PARP1-Val762Ala, XRCC1-Arg194Trp, XRCC1-Arg399Gln, XPC-Lys939Gln,
      BRCA1-Lys1183Arg, and BRCA2-Asn372His) and the clinical outcome of patients with
      primary small cell carcinoma of esophagus (SCCE), and it showed that the median
      progression-free survival (PFS) and the overall survival (OS) were 11.8 versus
      9.7 months (P = 0.041) and 17.4 versus 14.8 months (P = 0.032) for patients
      carrying the variant allele (T/C + C/C) and the wild-type allele (T/T) of PARP1
      Val762Ala polymorphism, respectively. However, no statistical significance was
      observed in the other five polymorphic loci (P > 0.05). When these six SNPs were
      combined, however, patients with at least three variant genotypes had
      significantly longer PFS and OS compared with those carrying less than three
      variant genotypes (P = 0.009 and P = 0.007, respectively). The presence of at
      least three polymorphic variants in certain DNA repair genes may impact on
      patient survival and could be a potential genomic predictor of clinical response
      to DNA-damaging treatment in SCCE patients.

PMID- 25374064
TI  - A Huaier polysaccharide inhibits hepatocellular carcinoma growth and metastasis.
AB  - This study was carried out to evaluate the effects of a Huaier polysaccharide (TP
      1) on the tumor growth and immune function in hepatocellular carcinoma (HCC) H22
      based mouse in vivo. Results showed that TP-1 was capable of repressing
      transplanted H22 solid hepatic tumor cell growth in vivo, prolonging the live
      time of mice bearing ascetic H22 tumors, and repressing the pulmonary metastasis
      of H22-bearing mice. Moreover, the relative weight of immune organ (spleen and
      thymus) and lymphocyte proliferation were improved after TP-1 treatment.
      Furthermore, the treatment with TP-1 could promote immune-stimulating serum
      cytokines, such as IL-2 and IFN-gamma, but inhibit immune-suppressing serum
      cytokines IL-10 secretion in H22-bearing mice. Besides, the percentage of CD4+ T
      cells and NK cells was increased, whereas the number of CD8+ T cells decreased in
      tumor-bearing mice following TP-1 administration. In addition, this compound
      displayed little toxic effects to major organ of tumor-bearing mice at the
      therapeutic dose, such as the liver and kidney. This experimental finding
      suggested that TP-1 exhibited prominent antitumor activities in vivo via
      enhancement of host immune system function in H22 tumor-bearing mice. This
      product could be developed individually as a safe and potent biological response
      modifier for HCC therapy. 

PMID- 25374065
TI  - A novel Alu-based real-time PCR method for the quantitative detection of plasma
      circulating cell-free DNA: sensitivity and specificity for the diagnosis of
      myocardial infarction.
AB  - In the present study, we aimed to develop and validate a rapid and sensitive, Alu
      based real-time PCR method for the detection of circulating cell-free DNA
      (cfDNA). This method targeted repetitive elements of the Alu reduplicative
      elements in the human genome, followed by signal amplification using fluorescence
      quantification. Standard Alu-puc57 vectors were constructed and 5 pairs of
      specific primers were designed. Valuation was conducted concerning linearity,
      variation and recovery. We found 5 linear responses (R1-5=0.998-0.999). The
      average intra- and inter-assay coefficients of variance were 12.98 and 10.75%,
      respectively. The recovery was 82.33-114.01%, with a mean recovery index of
      101.26%. This Alu-based assay was reliable, accurate and sensitive for the
      quantitative detection of cfDNA. Plasma from normal controls and patients with
      myocardial infarction (MI) were analyzed, and the baseline levels of cfDNA were
      higher in the MI group. The area under the receiver operating characteristic
      (ROC) curve for Alu1, Alu2, Alu3, Alu4, Alu5 and Alu (Alu1 + Alu2 + Alu3 + Alu4 +
      Alu5) was 0.887, 0.758, 0.857, 0.940, 0.968 and 0.933, respectively. The optimal
      cut-off value for Alu1, Alu2, Alu3, Alu4, Alu5 and Alu to predict MI was 3.71,
      1.93, 0.22, 3.73, 6.13 and 6.40 log copies/ml. We demonstrate that this new
      method is a reliable, accurate and sensitive method for the quantitative
      detection of cfDNA and that it is useful for studying the regulation of cfDNA in
      certain pathological conditions. Alu4, Alu5 and Alu showed better sensitivity and
      specificity for the diagnosis of MI compared with cardiac troponin I (cTnI),
      creatine kinase MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH). Alu5 had
      the best prognostic ability.

PMID- 25374066
TI  - Sexually dimorphic genetic architecture of complex traits in a large-scale F2
      cross in pigs.
AB  - BACKGROUND: It is common for humans and model organisms to exhibit sexual
      dimorphism in a variety of complex traits. However, this phenomenon has rarely
      been explored in pigs. RESULTS: To investigate the genetic contribution to sexual
      dimorphism in complex traits in pigs, we conducted a sex-stratified analysis on
      213 traits measured in 921 individuals produced by a White Duroc * Erhualian F2
      cross. Of the 213 traits examined, 102 differed significantly between the two
      sexes (q value <0.05), which indicates that sex is an important factor that
      influences a broad range of traits in pigs. We compared the estimated
      heritability of these 213 traits between males and females. In particular, we
      found that traits related to meat quality and fatty acid composition were
      significantly different between the two sexes, which shows that genetic factors
      contribute to variation in sexual dimorphic traits. Next, we performed a genome
      wide association study (GWAS) in males and females separately; this approach
      allowed us to identify 13.6% more significant trait-SNP (single nucleotide
      polymorphism) associations compared to the number of associations identified in a
      GWAS that included both males and females. By comparing the allelic effects of
      SNPs in the two sexes, we identified 43 significant sexually dimorphic SNPs that
      were associated with 22 traits; 41 of these 43 loci were autosomal. The most
      significant sexually dimorphic loci were found to be associated with muscle hue
      angle and Minolta a* values (which are parameters that reflect the redness of
      meat) and were located between 9.3 and 10.7 Mb on chromosome 6. A nearby gene
      i.e. NUDT7 that plays an important role in heme synthesis is a strong candidate
      gene. CONCLUSIONS: This study illustrates that sex is an important factor that
      influences phenotypic values and modifies the effects of the genetic variants
      that underlie complex traits in pigs; it also emphasizes the importance of
      stratifying by sex when performing GWAS.

PMID- 25374067
TI  - microRNA-338-3p functions as a tumor suppressor in human non-small-cell lung
      carcinoma and targets Ras-related protein 14.
AB  - microRNAs (miRNAs) have been demonstrated to be important gene regulators with
      critical roles in diverse biological processes, including tumorigenesis.
      Accumulating evidence suggests that miR-338-3p exerts a tumor suppressor role and
      is downregulated in tumors, including gastric cancer and colorectal carcinoma.
      However, the role of miR-338-3p in lung cancer, particularly non-small-cell lung
      carcinoma (NSCLC), has remained elusive. In the present study, the expression
      levels of miR-338-3p in NSCLC tissues were compared with those of matched normal
      tissues by use of polymerase chain reaction analysis. miR-338-3p was shown to be
      downregulated in NSCLC tissues, and the expression levels of miR-338-3p were
      significantly correlated with NSCLC cancer differentiation, pathological stage
      and lymph-node metastasis. Ectopic miR-338-3p expression significantly suppressed
      the in vitro proliferation and colony formation of NSCLC cells and enhanced
      apoptosis. Of note, ectopic miR-338-3p expression significantly inhibited Ras
      related protein 14 (RAB14) mRNA and protein expression, and reduced luciferase
      reporter activity containing the RAB14 3'-untranslated region through the first
      binding site. These findings suggested that miR-338-3p regulated the survival of
      NSCLC cells partially through the downregulation of RAB14. Therefore, targeting
      the miR-338-3p/RAB14 interaction may serve as a novel therapeutic application to
      treat NSCLC patients.

PMID- 25374068
TI  - Hot pressing to enhance the transport Jc of Sr0.6K0.4Fe2As2 superconducting
      tapes.
AB  - High-performance Sr0.6K0.4Fe2As2 (Sr-122) tapes have been successfully fabricated
      using hot pressing (HP) process. The effect of HP temperatures (850-925 degrees
      C) on the c-axis texture, resistivity, Vickers micro-hardness, microstructure and
      critical current properties has been systematically studied. Taking advantage of
      high degree of c-axis texture, well grain connectivity and large concentration of
      strong-pinning defects, we are able to obtain an excellent Jc of 1.2 * 10(5)
      A/cm(2) at 4.2 K and 10 T for Sr-122 tapes. More importantly, the field
      dependence of Jc turns out to be very weak, such that in 14 T the Jc still
      remains ~ 1.0 * 10(5) A/cm(2). These Jc values are the highest ever reported so
      far for iron-pnictide wires and tapes, achieving the level desired for practical
      applications. Our results clearly strengthen the position of iron-pnictide
      conductors as a competitor to the conventional and MgB2 superconductors for high
      field applications.

PMID- 25374069
TI  - Correction: Synthetic chemistry fuels interdisciplinary approaches to the
      production of artemisinin.

PMID- 25374070
TI  - Molecular and bacteriological investigation of subclinical mastitis caused by
      Staphylococcus aureus and Streptococcus agalactiae in domestic bovids from
      Ismailia, Egypt.
AB  - A study was carried out to establish the prevalence of subclinical mastitis (SCM)
      in smallholder dairy farms in Ismailia, Egypt. A total of 340 milking cows and
      buffaloes were sampled from 60 farms, and 50 nasal swabs were collected from
      consenting farm workers. Milk samples were subjected to California mastitis test
      (CMT) and the positive samples were examined by bacterial culture and PCR to
      identify etiological agents. Based on CMT, the prevalence of SCM was 71.6 % in
      cattle and 43.5 % in buffaloes while the prevalence was 25.2 % at cow-quarter
      level and 21.7 % at buffaloes-quarter level. Bacteriological analysis showed that
      the most frequently identified bacteria were Staphylococcus (S.) aureus (38.3 %)
      and Streptococcus (Str.) agalactiae (20 %). The diagnostic sensitivity of PCR
      compared to bacterial culture was superior with S. aureus and Str. agalactiae
      detection being 41 and 22.6 %, respectively. Furthermore, methicillin-resistant
      S. aureus (MRSA) strains occurred in 52.2 and 45 % of isolates of animals and
      workers, respectively. Subclinical mastitis due to S. aureus and Str. agalactiae
      is endemic in smallholder dairy herds in Ismailia. The occurrence of MRSA in
      animals and workers highlights a need for wide epidemiological studies of MRSA
      and adopting control strategies. 

PMID- 25374071
TI  - [Inhibition of PI3K/AKT signaling pathway promotes the nuclear translocation of
      B7-H4].
AB  - OBJECTIVE: To investigate the regulatory effect of phosphatidylinositol-3
      kinase/protein kinase B (PI3K/AKT) signaling pathway on the subcellular
      distribution of negative co-stimulatory molecule B7-H4. METHODS: The HEK293 cells
      transfected stably with B7-H4, named B7-H4/HEK293, were treated with the PI3K/AKT
      specific inhibitor LY294002 and/or the nuclear export inhibitor leptomycin B
      (LMB). The subcellular localization of B7-H4 in B7-H4/HEK293 was observed by
      immunofluorescence and confocal laser scanning microscopy (CLSM), and the
      expression levels of B7-H4 in membrane, cytoplasm and nuclear were detected by
      Western blotting. RESULTS: CLSM showed that LY294002 effectively induced the
      nuclear translocation of B7-H4 when compared with vehicle group. When the B7
      H4/HEK293 cells were treated with LY294002 and LMB, more B7-H4 was translocated
      into nuclear. Western blotting demonstrated that after the PI3K/AKT signal
      pathway was inhibited by LY294002 for 24 hours, the levels of B7-H4 in cell
      membrane and cytoplasm decreased significantly (P<0.05), while the expression in
      nuclear increased significantly (P<0.05). CONCLUSION: The PI3K/AKT signal pathway
      might inhibit the nuclear translocation of B7-H4.

PMID- 25374072
TI  - [Adrenomedullin inhibits TGF-beta1-induced procollagen expression in cultured
      human fetal lung fibroblasts via Smad2/3 pathway].
AB  - OBJECTIVE: To observe the effects of adrenomedullin (AM) on transforming growth
      factor- beta1 (TGF-beta1) induced the expression of procollagen type 1 alpha 1
      (Col1alpha1) and procollagen type 3 alpha 1 (Col3alpha1) as well as Smad2/3
      phosphorylation in human fetal lung fibroblasts (HFLFs). METHODS: Primary HFLFs
      were cultured in vitro. After treated with TGF-beta1 and/or AM, the expression
      levels of Col1alpha1 and Col3alpha1 mRNA were determined by reverse transcription
      PCR (RT-PCR), and phospho-Smad2/3 (p-Smad2/3) protein levels in HFLFs were
      measured by Western blotting. RESULTS: TGF-beta1 increased the gene expression
      levels of Col1alpha1 and Col3alpha1, and promoted the phosphorylation levels of
      Smad2/3 protein in HFLFs. AM significantly reversed the expression level of
      Col3alpha1 mRNA, and inhibited p-Smad2/3 expression in HFLFs induced by TGF
      beta1. CONCLUSION: AM could inhibit TGF-beta1-induced the procollagen expression
      in cultured HFLFs possibly through the Smad2/3 signaling pathway.

PMID- 25374073
TI  - [Enhancement of mouse immune response by recombinant adenovirus co-expressing VP1
      2A of foot-and-mouth disease virus and porcine IFN-alpha].
AB  - OBJECTIVE: To construct the recombinant adenovirus co-expressing foot-and-mouth
      disease virus (FMDV) viral structural protein1-2A (VP1-2A) and porcine interferon
      alpha (poIFN-alpha), and study its impact on mouse adaptive immune responses.
      METHODS: FMDV VP1-2A genes and porcine IFN-alpha (poIFN-alpha) genes were
      successively cloned into pAdeno Vator-CMV5-IRES-GFP, and then both pAdeno Vator
      CMV5-IRES-GFP with VP1-2A-poIFN-alpha and pAdeno Vator DeltaE1/E3 were co
      transfected into E.coli BJ5183 competent cells. The homologous recombinant
      plasmid rAd5VP1-2A-poIFN-alpha was screened and linearized by Pac I to expose the
      encapsidation signal and then transfected into HEK293A cells by
      Lipofectamine(TM)2000. The positive recombinant viruses were named rAd5VP1-2A
      poIFN-alpha. The BALB/c mice were immunized by the recombinant adenovirus rAd5VP1
      2A-poIFN-alpha or rAd5VP1 (adenoviral vectors solely expressing FMDV VP1) or
      blank adenovirus as control (Ad virus). The FMDV VP1-specific IgG, IgG1, IgG2a
      and cytokines IL-4, IFN-gamma were determined by the ELISA, and the index of
      peripheral blood lymphocyte proliferation was detected by MTT assay. RESULTS: The
      recombinant adenovirus co-expressing FMDV VP1-2A and porcine IFN-alpha (rAd5VP1
      2A-poIFN-alpha) was successfully constructed. ELISA and MTT assay showed that
      compared with rAd5VP1 group, rAd5VP1-2A-poIFN-alpha could enhance the secretion
      of FMDV VP1-specific IgG, IgG1 and IgG2a, promote the secretion of IL-4 and IFN
      gamma, and increase the index of peripheral blood lymphocyte proliferation.
      CONCLUSION: The rAd5VP1-2A-poIFN-alpha could significantly improve the mouse
      adaptive immune responses.

PMID- 25374074
TI  - [Immunoprotective effect of a plasmid DNA vaccine pCMV-LC3-Ag85B against
      Mycobaterium tuberculosis].
AB  - OBJECTIVE: To construct an autophagy-targeted vaccine harboring the genes
      encoding Ag85B and microtubule-associated protein light chain-3 (LC3) and to
      explore its immunoprotection against Mycobacterium tuberculosis (MTB). METHODS:
      The pCMV-LC3-Ag85B plasmid was constructed and used to transfect RAW264.7 cells.
      The level of LC3-Ag85B was detected using Western blotting. Then, BALB/c mice
      were immunized with pCMV, pCMV-Ag85B and pCMV-LC3-Ag85B plasmid, respectively. In
      vitro, two weeks after the last immunization, the secretion of IL-2, IFN-gamma,
      IL-4 and IL-10 from Ag85B-stimulated lymphocytes was measured by ELISA. Three
      months after the last immunization, all mice were challenged with MTB H37Rv via
      the tail vein and the bacterial loads in their spleens and lungs were determined
      by colony formation assay. RESULTS: The LC3-Ag85B fusion protein was expressed in
      RAW264.7 cells that had been transfected with pCMV-LC3-Ag85B and the expression
      level was in a dose-dependent manner. Compared with the pCMV-Ag85B treatment
      group, pCMV-LC3-Ag85B-immunized mice showed a significant increase of IL-2 and
      IFN-gamma levels and the lower loads of MTB in the spleens and lungs. CONCLUSION:
      pCMV-LC3-Ag85B can enhance a specific Th1-predominant immunity and a superior
      immunoprotection against MTB, which may provide a new practical strategy for the
      development of improved vaccines against MTB.

PMID- 25374075
TI  - [Establishment and identification of human hepatocellular carcinoma line stably
      expressing hepatitis C virus core protein].
AB  - OBJECTIVE: To establish SMMC-7721 human hepatocellular carcinoma cell line stably
      expressing hepatitis C virus (HCV) core protein. METHODS: A lentiviral vector
      containing HCV core gene was constructed and transfected into HEK293T cells to
      package recombinant lentivirus (rLV-core) containing ZsGreen and HCV core genes.
      The SMMC-7721 cells were infected with the rLV-core. The expression of HCV core
      mRNA was examined by real-time fluorescent quantitative PCR and the HCV core
      protein was detected by immunofluorescence cytochemistry and Western blotting.
      The stably transfected cell line was screened. RESULTS: The lentiviral vector was
      confirmed by enzyme digestion and sequencing. The green fluorescence was seen
      under fluorescence microscope 48 hours after virus packaging. The SMMC-7721 cell
      line stably expressing HCV core protein was obtained after infected with the rLV
      core. Real-time PCR showed the expression of HCV core mRNA, and both
      immunofluorescence cytochemistry and Western blotting verified the expression of
      HCV core protein. CONCLUSION: The SMMC-7721 human hepatocellular carcinoma cell
      line stably expressing HCV core protein has been established successfully.

PMID- 25374076
TI  - [The humoral immune response in mice induced by recombinant Lactococcus lactis
      expressing HIV-1 gag].
AB  - OBJECTIVE: To analyze the humoral immune response induced by recombinant
      Lactococcus lactis expressing HIV-1 gag in mice immunized orally, intranasally,
      subcutaneously or in the combined way of above three. METHODS: Fifty BALB/c mice
      were randomly divided into 5 groups, 10 mice per group. The mice were immunized
      consecutively three times at two week intervals with 10(9) CFU of recombinant
      Lactococcus lactis expressing gag through oral, intranasal, subcutaneous
      administration or the mix of them. The mice that were immunized orally with
      Lactococcus lactis containing PMG36e served as a control group. The sera of mice
      were collected before primary immunization and 2 weeks after each immunization to
      detect the gag specific IgG by ELISA. RESULTS: Compared with the control group,
      the higher titer of serum gag specific IgG was detected in the four groups
      immunized with recombinant Lactococcus lactis expressing gag, and it was the
      highest in the mixed immunization group (P<0.01). The titer of serum gag specific
      IgG from the oral and subcutaneous immunization groups was significantly higher
      than that from the intranasal immunization group (P<0.01) 6 weeks after primary
      immunization . The serum antibody positive rates of the oral immunization group
      after the first, the second, the third immunization were 40%, 40%, 90%,
      respectively; the positive rates of the intranasal immunization group were 10%,
      20%, 20%; the positive rates of the subcutaneous immunization group were 10%,
      60%, 90%; the positive rate of the combined immunization group reached 100% 2
      weeks after primary immunization. CONCLUSION: Recombinant Lactococcus lactis
      expressing gag can induce humoral immune response in mice by oral, intranasal,
      subcutaneous injection or the mix of them, and the mixed immunization can enhance
      the immune effects of Lactococcus lactis vector vaccine.

PMID- 25374077
TI  - [Enolase of Streptococcus suis serotype 2 is involved in the antiphagocytosis of
      Streptococcus suis].
AB  - OBJECTIVE: To prepare the recombinant enolase of Streptococcus suis (SsEno),
      analyze the effect of SsEno on the antiphagocytosis by antibody-blocking assay in
      the human blood bactericidal model, and identify the human fibrinogen (hFg)
      binding activity of SsEno protein. METHODS: SsEno gene was amplified using the
      primers designed according to 05ZYH33 genome sequences and cloned into the
      expression vector pET28a to construct recombinant plasmids. The plasmids were
      transformed into E.coli BL21(DE3) and induced to express by IPTG. The expression
      level was analyzed by SDS-PAGE. The recombinant proteins were purified by nickel
      affinity chromatography and identified by Western blotting. High-titer specific
      antiserum against SsEno was prepared by immunizing rabbits with the purified
      recombinant proteins. The impact of SsEno on antiphagocytosis was analyzed by
      antibody-blocking assay in the human blood bactericidal model. In addition, the
      specific binding activity with hFg was identified by Far-Western blotting and
      ELISA. RESULTS: The prokaryotic expression vector of hisSsEno (SsEno with His
      tag) was constructed and high-purity recombinant expressed protein was purified.
      In specific antibody blocking assay, antiserum against the SsEno significantly
      decreased the percent of survival bacteria as observed in high virulent strain
      05ZYH33. Additionally, hisSsEno was proved to have the specific binding activity
      with hFg. CONCLUSION: SsEno was found to be a potential antiphagocytic factor of
      S. suis with a specific binding to hFg, suggesting that SsEno play an important
      role in antiphagocytosis of S. suis.

PMID- 25374078
TI  - [Adenovirus-mediated interleukin-24 enhances the inhibitory effect of paclitaxel
      on the growth of lung cancer A549 cells].
AB  - OBJECTIVE: To investigate the effect of adenovirus-mediated interleukin-24 (Ad-IL
      24) combined with paclitaxel on the growth of human lung cancer A549 cells in
      vitro. METHODS: A549 cells were treated with Ad-IL-24 alone, paclitaxel alone and
      Ad-IL-24 combined with paclitaxel, respectively. Their proliferation was detected
      by CCK-8 assay, and the changes of apoptosis and cell cycle were tested by flow
      cytometry. RESULTS: The treatment of Ad-IL-24 significantly inhibited the A549
      cell growth and induced cell apoptosis. Compared with paclitaxel alone and Ad-IL
      24 alone, the Ad-IL-24 plus paclitaxel treatment more evidently inhibited lung
      cancer cell growth and increased cell apoptosis rate, and induced G2/M phase
      arrest. CONCLUSION: Ad-IL-24 infection can enhance the inhibitory effect of
      paclitaxel on lung cancer cell growth.

PMID- 25374079
TI  - [Establishment of breast cancer MDA-MB-231 cell line stably over-expressing human
      TOX high mobility group box family member 3].
AB  - OBJECTIVE: To construct the lentiviral expression vector of human TOX high
      mobility group box family member 3 (TOX3) gene and the MDA-MB-231 cell line which
      stably over-expresses TOX3 gene. METHODS: TOX3 gene was synthesized by the gene
      synthesis method and amplified by PCR, and then cloned into pLVEF-1a/GFP-Puro
      vector to construct pLVEF-1a/GFP-Puro-TOX3 lentiviral vector. After restriction
      enzyme analysis and sequence identification, the lentiviral vector was packaged
      and the titer was detected. The human breast cancer MDA-MB-231 cells were
      transfected with the recombinant lentiviral vector and cultured selectively by
      puromycin to acquire stably transfected cells. MDA-MB-231 cells which expressed
      GFP were observed by fluorescence microcopy. And the expression levels of TOX3
      mRNA and protein in transfected MDA-MB-231 cells were detected by real-time
      quantitative PCR(qRT-PCR) and Western blotting, respectively. RESULTS:
      Restriction enzyme digestion and sequence analysis demonstrated that the
      lentiviral expression vectors of pLVEF-1a/GFP-Puro and pLVEF-1a/GFP-Puro-TOX3
      were successfully constructed, and the viral titers were respectively 2*10(8)
      TU/mL and 1*10(8) TU/mL after lentiviral packaging. And after being transfected,
      more than 95% cells expressed GFP under a fluorescence microscope. The results of
      qRT-PCR and Western blotting showed that, when compared with the MDA-MB-231-NC
      negative control group, the expression of TOX3 mRNA and protein significantly
      increased in the MDA-MB-231-TOX3 group. CONCLUSION: The study successfully
      constructed lentiviral expression vector of TOX3 gene and obtained MDA-MB-231
      cell line stably over-expressing TOX3 gene by transfection with the recombinant
      vector.

PMID- 25374080
TI  - [Expression of IkappaBalpha in bladder cancer cell lines is negatively correlated
      with epithelial-mesenchymal transition and cell invasion in vitro].
AB  - OBJECTIVE: To investigate the expression of inhibitor of nuclear factor
      kappaBalpha (IkappaBalpha) in bladder cancer cell lines and its correlation with
      epithelial-mesenchymal transition (EMT) and invasive potential in vitro. METHODS:
      The expressions of IkappaBalpha, epithelia cadherin (E-cadherin), neuronal
      cadherin (N-cadherin) and vimentin in human bladder cancer RT4, 5637, 235J, J82
      and T24 cell lines were detected by Western blotting. Invasive potential of these
      cell lines was evaluated by Transwell(TM) assay. In addition, morphological
      characteristics of those cells were carefully observed under a microscope.
      RESULTS: RT4 and 5637 cells exhibited epithelial cell morphological features, but
      253J, J82 and T24 cells had mesenchymal cell morphological features. E-cadherin
      was over-expressed in RT4 and 5637 cell lines, but the expressions of vimentin
      and N-cadherin could not been detected in the two cells. E-cadherin could be
      detected in 253J cells with a lower expression level; J82 and T24 cells had no
      expression of E-cadherin; vimentin and N-cadherin were highly expressed in 253J,
      J82 and T24 cells. Transwell(TM) assay showed higher invasive potential of 253J,
      J82 and T24 cells than RT4 and 5637 cells in vitro. In addition, RT4 and 5637
      cells expressed higher levels of IkappaBalpha than 253J, J82 and T24 cells.
      CONCLUSION: Expression of IkappaBalpha in human bladder cancer cells is
      negatively correlated with EMT and tumor invasion in vitro.

PMID- 25374081
TI  - [The expression and antibody preparation of S100A10 protein].
AB  - OBJECTIVE: To prepare S100A10 protein and its specific polyclonal antibody.
      METHODS: The full-length gene fragment of S100A10 was amplified by PCR, and then
      cloned into pET28a(+) prokaryotic expression vector. After transformation, the
      vector was induced to express the recombinant (S100A10)(2) protein by IPTG in
      E.coli BL21 (DE3). The recombinant (S100A10)(2) was then purified by Ni-NTA
      resin. (S100A10)(2)-specific polyclonal antibody was prepared using the purified
      recombinant (S100A10)(2) protein as antigen to inoculate rabbit intradermally.
      The title and specificity of the polyclonal antibody were determined by ELISA and
      Western blotting. RESULTS: The study successfully constructed the prokaryotic
      recombinant expression vector pET28a(+)-(S100A10)(2), and obtained the purified
      recombinant (S100A10)(2) protein and polyclonal antibody with high titer and
      specificity. CONCLUSION: The prokaryotic expression and purification system for
      S100A10 has been established and polyclonal antibody of (S100A10)(2) been
      prepared, which provides helpful fools for further researches on S100A10.

PMID- 25374082
TI  - [Effects of pH on the properties of colloidal gold labeling monoclonal antibody].
AB  - OBJECTIVE: To investigate the influence of pH on the properties of colloidal gold
      labeling monoclonal antibody (mAb). METHODS: The pH value of colloidal gold was
      adjusted by K(2)CO(3) solution. Then colloidal gold with a range of pH 5.0-9.0
      labeled enterovirus 71 (EV71)-VP1 mAb respectively, and bovine serum albumin
      (BSA) was added to block the unreacted sites on the gold colloids for further
      experiments. The changes in the properties of colloidal gold in the progress of
      colloidal gold labeling mAb were monitored by UV/Vis spectroscopy. Finally, Mey's
      test was adopted to identify the stability of immunogold, and the sensitivity of
      the strip was evaluated by detecting gradual dilution of serum. RESULTS: EV71-VP1
      mAb could be conjugated with colloidal gold at pH7.0-8.5, and at this optimal pH,
      the test strip presented a good sensitivity. CONCLUSION: pH is an important
      factor to ensure the stability of immunogold and to determine the conjugation
      effect between colloidal gold and mAb. The study confirmed that UV/Vis
      spectroscopy can evaluate the influence of pH on the properties of colloidal gold
      labeling mAb and set up an optimal pH for colloidal gold labeling using UV/Vis
      spectroscopy.

PMID- 25374083
TI  - [Human caspase-14 expression in malignant melanoma and its significance].
AB  - OBJECTIVE: To detect the caspase-14 expression in malignant melanoma cells and
      tumor tissues and its effect on tumor resistance to drug. METHODS: The mRNA and
      protein level of caspase-14 in 4 melanoma cell lines (A375, A875, M14, and SK-Mel
      1) and the melanocytes, was detected by reverse transcription PCR (RT-PCR) and
      Western blotting. Caspase-14 expression in 34 malignant melanoma tumor tissues
      and 10 dermal nevus tissues was determined by in situ hybridization and
      immunohistochemistry. RESULTS: Caspase-14 expression was seen in melanoma cells
      and melanocytes. It was higher in melanoma-associated antigen 1 recognized by T
      cells (MART-1) positive cells than in MART-1 negative cells. The cells expressing
      the lower caspase-14 were more sensitive to the treatment with either
      chemotherapy drugs camptothecin and cisplatin or radiotherapy than the ones
      expressing the higher caspase-14 (P<0.01). Caspase-14 expression was observed in
      70% dermal nevus, as well as 97% in malignant melanoma tissues, and the
      difference between them was statistically significant (P<0.05). CONCLUSION:
      Caspase-14 is expressed in tissues and cells of malignant melanoma. Our data
      indicated that the expression level of caspase-14 affected the drug sensitivity
      of melanoma.

PMID- 25374084
TI  - [Meta analysis of the changes of regulatory T cell number in patients with active
      systemic lupus erythematosus].
AB  - OBJECTIVE: To evaluate the change of regulatory T cells (Tregs) in patients with
      active systemic lupus erythematosus (SLE) using meta-analysis. METHODS: The
      PubMed and China Biomedical Literature (CBM) databases were searched for relevant
      studies up to August 31, 2013. After quality assessment and data extraction for
      included studies, a meta-analysis was performed using the software of
      Comprehensive-Meta Analysis (CMA) v2.2. RESULTS: Finally 22 case-control studies
      were recruited, including 12 studies reporting the change of Treg number and 12
      studies for the change of Treg:CD4(+)T cell ratio. The quality of studies was
      moderate to high. It demonstrated that the Treg number in peripheral blood
      mononuclear cells (PBMCs) of active SLE patients significantly decreased than
      ones in controls (WMD=-1.23%, %CI=-1.87% to -0.59%). Then, subgroup analysis was
      performed based on the different surface markers of Tregs. It showed that the
      Treg number in PBMCs of active SLE patients decreased by 1.56% for the
      CD4(+)CD25(+) Tregs (WMD=-1.56%, 95% CI=-2.18% to -0.94%), and by 0.91% for the
      CD4(+)CD25(high) Tregs (WMD=-0.91%, 95% CI=-1.52% to -0.29%) compared with ones
      in controls. As for the ratio of Tregs to CD4(+) T cells, there was no
      significant difference between the SLE patients and the controls. Sensitivity
      analysis showed the results were robust, and the Funnel Plots showed there was no
      publication bias. CONCLUSION: Based on the current evidences, the development of
      SLE may be due to the decrease of Treg number in PBMCs, not to the abnormal ratio
      of Tregs to CD4(+) T cells.

PMID- 25374085
TI  - [Abnormal proportions of immune regulatory cells and their subsets in peripheral
      blood of patients with Graves' disease].
AB  - OBJECTIVE: To evaluate the changes of various immune regulatory cells and their
      subsets in peripheral blood mononuclear cells (PBMCs) of patients with Graves'
      disease (GD). METHODS: Peripheral blood cells were obtained from 32 GD patients
      and 30 normal subjects. The proportions of regulatory T cells (Tregs), T helper 1
      (Th1) cells, Th2 cells, regulatory B cells (Bregs), dendritic cells (DCs) and
      their subsets in PBMCs were analyzed with flow cytometry. RESULTS: Compared with
      the normal subjects, the proportions of Tregs, Bregs and total DCs significantly
      decreased in PBMCs of the GD patients. However, the proportions of Th1, Th2 cells
      in PBMCs significantly increased in the GD patients compared with the normal
      subjects. As for DC subsets, the proportion of myeloid DCs (mDCs) dropped and
      plasmacytoid DCs (pDCs) went up in PBMCs of the GD patients compared with the
      normal subjects. Moreover, the proportion of mature DCs was raised in total DCs
      in the GD patients compared with normal subjects. CONCLUSION: There are disorders
      in various immune regulatory cells in PBMCs of the GD patients, which may play
      important roles in the onset and progression of GD.

PMID- 25374086
TI  - [Semi-quantitative detection of HPV L1 capsid protein in exfoliative cytological
      examination facilitates the differential diagnosis of cervical lesions].
AB  - OBJECTIVE: To evaluate the association of human papilloma virus (HPV) L1 capsid
      protein expression levels with cervical intraepithelial neoplasia (CIN) and its
      clinical significance. METHODS: Immunohistochemistry were performed to detect the
      expression of HPV L1 capsid protein in the cervical exfoliative cytological
      examination of 153 cases. The intensity (positive unit, PU) was assessed semi
      quantitatively using ImagePro Plus image analysis software. The results were
      evaluated based on histopathologic diagnosis of cervical biopsy. RESULTS: PU of
      HPV L1 capsid protein in different cytopathological groups, including
      normal/inflammation, atypical squamous cells of unknown significance (ASCUS), low
      grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial
      lesion (HSIL), was 46.87+/-24.46, 27.23+/-24.30, 24.10+/-22.45, 9.36+/-19.82,
      respectively, and the differences were statistically significant (P<0.01). PU of
      HPV L1 capsid protein in different histopathological groups, including normal
      cervixes or chronic cervicitis, LSIL and HSIL, was 41.30+/-26.66, 24.84+/-22.18,
      8.69+/-19.20, respectively, and the differences were statistically significant
      (P<0.01). Patients with high-risk HPV16 and HPV18 had significantly lower PU of
      HPV L1 capsid protein than those with other high-risk HPV (P<0.01). PU of HPV L1
      capsid protein were correlated negatively with both cytopathological groups and
      histopathological groups of cervical diseases (r=-0.458, P<0.01 and r=-0.441,
      P<0.01, respectively). PU of HPV L1 capsid protein was not associated with
      patients' age (P>0.05). CONCLUSION: Semi-quantitative analysis of HPV L1 capsid
      protein expression can directly reflect the precancerous progression of cervical
      cancer.

PMID- 25374087
TI  - [Detection of bilirubin, CCR1, troponin I and IL-6 in patients with acute
      myocardial infarction].
AB  - OBJECTIVE: To detect the levels of plasma C-C chemokine receptor type 1 (CCR1),
      serum total bilirubin (TBIL), troponin I and interleukin-6 (IL-6) in acute
      myocardial infarction (AMI) patients. METHODS: AMI group and control group
      respectively contained 65 samples. Diazo was used to detect the levels of serum
      TBIL, direct bilirubin (DBIL) and indirect bilirubin (IBIL). ELISA was used to
      detect the level of CCR1. Troponin I and IL-6 were detected by chemiluminescence
      analysis and radioimmunoassay, respectively. RESULTS: The levels of TBIL
      [(15.07+/-2.87) MUmol/L] and IBIL [(9.32+/-4.58) MUmol/L] were significantly
      lower in AMI group than in control group [TBIL (20.15+/-3.26) MUmol/L, IBIL
      (14.48+/-3.90) MUmol/L] (P<0.05). However, the levels of CCR1, troponin I and IL
      6 [(3.76+/- 0.85) ng/mL, (15.88+/-2.43) U/mL, (207.60+/- 23.94) U/mL] in AMI
      group were significantly higher than those in control group [CCR1 (0.66+/-0.19)
      ng/mL, troponin I (0.33+/-0.07) U/mL, IL-6 (103.55+/-16.86) U/mL] (P<0.05).
      CONCLUSION: The levels of CCR1, troponin I and IL-6 were increased and the level
      of serum bilirubin was decreased in AMI patients.

PMID- 25374088
TI  - [Early diagnostic values of CD64 and CD11b indices of peripheral white blood
      cells for acute exacerbation of chronic obstructive pulmonary disease in older
      adults].
AB  - OBJECTIVE: To investigate the values of CD64 and CD11b indices of peripheral
      white blood cells in the early diagnosis of acute exacerbation of chronic
      obstructive pulmonary disease (AE-COPD) in older adults. METHODS: The study
      enrolled 86 aged AE-COPD patients, 82 stable-COPD patients admitted in the
      affiliated hospital of Jiujiang University from March 2011 to December 2013, and
      simultaneously 84 healthy aged volunteers as a control group. All the subjects
      were examined in white blood cells, hypersensitive C-reactive protein (hs-CRP),
      mean fluorescence intensity (MFI) of CD64 and CD11b from peripheral white blood
      cells within 24 hours after admission. CD64 and CD11b MFI were converted into
      CD64 and CD11b indices by conversion formula. The significant indicators for the
      diagnosis of AE-COPD were screened and the receiver operating characteristic
      (ROC) curve was drawn for calculating the area under the curve, critical value,
      sensitivity and specificity. RESULTS: Compare with stable-COPD group, the CD11b
      index decreased and CD64 index increased. There existed statistical difference in
      CD11b and CD64 indices between the AE-COPD group and the stable-COPD group
      (P<0.01), but not between the stable-COPD group and the healthy control group
      (P>0.05). Critical values of CD11b and CD64 indices were respectively less than
      0.94 and more than 1.83. Their sensitively and specificity for the diagnosis of
      AE-COPD were 62.65% and 77.11% for CD11b and 79.52% and 98.80% for CD64.
      CONCLUSION: Increased CD64 index and decreased CD11b index are the credible
      laboratory markers in the early diagnosis of AE-COPD, and the dynamic monitoring
      of them may facilitate the evaluation of therapeutic outcomes of AE-COPD.

PMID- 25374089
TI  - [Bioinformatic analysis of mouse glucocorticoid-induced tumor necrosis factor
      receptor-related protein].
AB  - OBJECTIVE: To obtain the amino acid sequence of glucocorticoid-induced tumor
      necrosis factor receptor-related protein (GITR) of mouse with an attempt to
      predict the structure and function of GITR. METHODS: The amino acid sequence of
      GITR was analyzed by bioinformatic methods using the network platforms and some
      bioinformatic softwares. RESULTS: The amino acid sequence of mouse GITR showed a
      homology of 56% with that of other species, including human. GITR protein was
      composed of signal peptide, extracellular region, transmembrane domain and
      intracellular region. The extracellular region of mouse GITR is located at the
      position of 22-153 amino acid residues. The sequence of mGITR might contain four
      N-glycosylation sites, four serine phosphorylation sites, one threonine
      phosphorylation site and one tyrosine phosphorylation site. CONCLUSION: The
      bioinformatic analysis of mouse GITR could provide a basis for the further
      expression and functional study of mouse GITR protein.

PMID- 25374090
TI  - [Comparison between annexin V-FITC/PI and Hoechst33342/PI double stainings in the
      detection of apoptosis by flow cytometry].
AB  - OBJECTIVE: To evaluate the merits and demerits of annexin V-FITC/PI and
      Hoechst33342/PI double stainings in the detection of apoptosis by flow cytometry.
      METHODS: Hoechst33342/PI and annexin V-FITC/PI double stainings were performed to
      detect the apoptosis of thymocytes induced by DEX and K562 cells induced by
      H(2)O(2). RESULTS: The anenxin V-FITC/PI double staining was able to detect the
      cell apoptosis in both DEX-induced thymocytes and H(2)O(2)-induced K562 cells as
      predicted, and the cell plotting was consistent with the principle of the method.
      Hoechest33342/PI double staining was able to detect cell apoptosis in the DEX
      induced thymocytes, but this method showed a contradictory result in the early
      stage of H(2)O(2)-induced K562 cell apoptosis, and the cell plotting was in
      conflict with the principle of the method. CONCLUSION: Compared with annexin V
      FITC/PI double staining, the method of Hoechst33342/PI double staining in the
      detection of apoptosis by flow cytometry has some limitations.

PMID- 25374091
TI  - To the dumpster.

PMID- 25374092
TI  - Provision of chlamydia testing, and training of primary health care staff about
      chlamydia testing, across four European countries.
AB  - BACKGROUND: The objectives of this study were to describe and compare chlamydia
      testing provided by general practitioners (GPs) in four selected European
      countries with well-developed primary health care systems and high reported
      chlamydia rates; we aimed to compare contrasting countries where chlamydia
      testing is provided by GPs (England, Sweden) with countries where primary care
      chlamydia testing is absent or very limited (France, Estonia). METHODS: For data
      generation a structured questionnaire was developed and secondary data sources
      were searched. The questionnaire developed by the research team allowed a
      systematic approach to analysing chlamydia care (including testing in general
      practice) and the gathering of relevant data. RESULTS: There were no significant
      differences in the burden of the disease or the type of general practice care
      provision in the study countries. In all four countries, testing for chlamydia
      (with nucleic acid amplification test, NAAT) is available in the public sector, a
      substantial proportion (>60%) of young people aged 16-25 years visit their
      general practitioner (GP) annually, and reimbursement for chlamydia testing costs
      to the relevant parties (GPs in England, Sweden and Estonia; and patients in
      France) by the national health insurance system or its equivalent.In countries
      where chlamydia testing is provided by GPs (England, Sweden) a national strategy
      or plan on STI control that specifically mentions chlamydia was in force,
      chlamydia care guidelines for GPs were in place and STI management was more
      firmly established in the GP residency training curriculum, either formally
      (England) or informally (Sweden), than in the other countries. CONCLUSION: Future
      research on the effectiveness of chlamydia screening (also in the context of
      general practice care) and program provision should reflect national needs and
      the prevention of complications.

PMID- 25374093
TI  - Nutrition labelling of pre-packaged foods in Belgrade, Serbia: current situation.
AB  - OBJECTIVE: To determine the presence of nutrition labels on pre-packaged food
      products, as well as to analyse the types of presentation. DESIGN: This was a
      descriptive study. The following characteristics were analysed: (i) presence and
      placement of the nutrition declaration (either as front-of-pack (FOP) or back-of
      pack (BOP)); (ii) content of the presented information; (iii) presence of
      nutrition and health claims; and (iv) legibility of the written information.
      Settings Three different types of retailers in Belgrade, Serbia. SUBJECTS: A
      total of 2138 pre-packaged food products from ten categories. RESULTS: A
      nutrition declaration was found on 65.9% of all tested products. It was displayed
      on the back of the packaging of 62.7% of products and on the front of the
      packaging of 19.1% of products. BOP was the most commonly observed in breakfast
      cereals, soft drinks, milk and instant soups (in total over 90%), and the least
      common in meat products (21.5%). FOP was predominantly displayed on breakfast
      cereals (65.0%) and the least frequently on milk products (2.4%). The 'Big 4'
      (energy value, protein, carbohydrate and fat contents) and the 'Big 4 with
      additional information' figured on 40.9% of products. The 'Big 8' ('Big 4' plus
      sugar, saturated fat, fibre and sodium contents) and the 'Big 8 with additional
      information' were present less frequently (20.5%). Nutrition claims and health
      claims appeared on very few products (6.6% and 6.3%, respectively). The
      proportion of products with insufficient legibility was 31.5%. CONCLUSIONS:
      Nutrition labelling in Belgrade, Serbia is not satisfactory. Mandatory
      regulations may be the best way to improve the current situation.

PMID- 25374094
TI  - Cocaine increases dopaminergic neuron and motor activity via midbrain alpha1
      adrenergic signaling.
AB  - Cocaine reinforcement is mediated by increased extracellular dopamine levels in
      the forebrain. This neurochemical effect was thought to require inhibition of
      dopamine reuptake, but cocaine is still reinforcing even in the absence of the
      dopamine transporter. Here, we demonstrate that the rapid elevation in dopamine
      levels and motor activity elicited by cocaine involves alpha1 receptor activation
      within the ventral midbrain. Activation of alpha1 receptors increases
      dopaminergic neuron burst firing by decreasing the calcium-activated potassium
      channel current (SK), as well as elevates dopaminergic neuron pacemaker firing
      through modulation of both SK and the hyperpolarization-activated cation currents
      (Ih). Furthermore, we found that cocaine increases both the pacemaker and burst
      firing frequency of rat ventral-midbrain dopaminergic neurons through an alpha1
      adrenergic receptor-dependent mechanism within the ventral tegmental area and
      substantia nigra pars compacta. These results demonstrate the mechanism
      underlying the critical role of alpha1 adrenergic receptors in the regulation of
      dopamine neurotransmission and behavior by cocaine. 

PMID- 25374095
TI  - Neurocognitive effects of ketamine and association with antidepressant response
      in individuals with treatment-resistant depression: a randomized controlled
      trial.
AB  - The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays
      rapid antidepressant effects in patients with treatment-resistant depression
      (TRD); however, the potential for adverse neurocognitive effects in this
      population has not received adequate study. The current study was designed to
      investigate the delayed neurocognitive impact of ketamine in TRD and examine
      baseline antidepressant response predictors in the context of a randomized
      controlled trial. In the current study, 62 patients (mean age = 46.2 +/- 12.2)
      with TRD free of concomitant antidepressant medication underwent neurocognitive
      assessments using components of the MATRICS Consensus Cognitive Battery (MCCB)
      before and after a single intravenous infusion of ketamine (0.5 mg/kg) or
      midazolam (0.045 mg/kg). Participants were randomized to ketamine or midazolam in
      a 2:1 fashion under double-blind conditions and underwent depression symptom
      assessments at 24, 48, 72 h, and 7 days post treatment using the Montgomery
      Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive assessment
      was conducted once at 7 days. Neurocognitive performance improved following the
      treatment regardless of treatment condition. There was no differential effect of
      treatment on neurocognitive performance and no association with antidepressant
      response. Slower processing speed at baseline uniquely predicted greater
      improvement in depression at 24 h following ketamine (t = 2.3, p = 0.027), while
      controlling for age, depression severity, and performance on other neurocognitive
      domains. In the current study, we found that ketamine was devoid of adverse
      neurocognitive effects at 7 days post treatment and that slower baseline
      processing speed was associated with greater antidepressant response. Future
      studies are required to further define the neurocognitive profile of ketamine in
      clinical samples and to identify clinically useful response moderators.

PMID- 25374096
TI  - Species differences in cannabinoid receptor 2 and receptor responses to cocaine
      self-administration in mice and rats.
AB  - The discovery of functional cannabinoid receptors 2 (CB2Rs) in brain suggests a
      potential new therapeutic target for neurological and psychiatric disorders.
      However, recent findings in experimental animals appear controversial. Here we
      report that there are significant species differences in CB2R mRNA splicing and
      expression, protein sequences, and receptor responses to CB2R ligands in mice and
      rats. Systemic administration of JWH133, a highly selective CB2R agonist,
      significantly and dose-dependently inhibited intravenous cocaine self
      administration under a fixed ratio (FR) schedule of reinforcement in mice, but
      not in rats. However, under a progressive ratio (PR) schedule of reinforcement,
      JWH133 significantly increased breakpoint for cocaine self-administration in
      rats, but decreased it in mice. To explore the possible reasons for these
      conflicting findings, we examined CB2R gene expression and receptor structure in
      the brain. We found novel rat-specific CB2C and CB2D mRNA isoforms in addition to
      CB2A and CB2B mRNA isoforms. In situ hybridization RNAscope assays found higher
      levels of CB2R mRNA in different brain regions and cell types in mice than in
      rats. By comparing CB2R-encoding regions, we observed a premature stop codon in
      the mouse CB2R gene that truncated 13 amino-acid residues including a functional
      autophosphorylation site in the intracellular C-terminus. These findings suggest
      that species differences in the splicing and expression of CB2R genes and
      receptor structures may in part explain the different effects of CB2R-selective
      ligands on cocaine self-administration in mice and rats. 

PMID- 25374097
TI  - Haemostaseome-associated SNPs: has the thrombotic phenotype a greater influence
      than ethnicity? GMT study from Aquitaine including Basque individuals.
AB  - The Genetic Markers for Thrombosis (GMT) study compared the relative influence of
      ethnicity and thrombotic phenotype regarding the distribution of SNPs implicated
      in haemostasis pathophysiology ("haemostaseome"). We assessed 384 SNPs in three
      groups, each of 480 subjects: 1) general population of Aquitaine region
      (Southwestern France) used as control; 2) patients with venous thromboembolism
      from the same area; and 3) autochthonous Basques, a genetic isolate, who
      demonstrate unusual characteristics regarding the coagulation system. This study
      sought to evaluate i) the value of looking for a large number of genes in order
      to identify new genetic markers of thrombosis, ii) the value of investigating low
      risk factors and potential preferential associations, iii) the impact of
      ethnicity on the characterisation of markers for thrombosis. We did not detect
      any previously unrecognised SNP significantly associated with thrombosis risk or
      any preferential associations of low-risk factors in patients with thrombosis.
      The sum of kappa2 values for our 110 significant SNPs demonstrated a smaller
      genetic distance between patients and controls (321 cumulated kappa2 value) than
      between Basques and controls (1,570 cumulated kappa2 value). Hence, our study
      confirms the genetic particularity of Basques especially regarding a
      significantly lower expression of the non-O blood group (p< 0.0004). This is
      mitigated by a higher prevalence of factor II Leiden (p< 0.02) while factor V
      Leiden prevalence does not differ. Numerous other differences covering a wide
      range of proteins of the haemostaseome may result in an overall different genetic
      risk for venous thromboembolism. 

PMID- 25374098
TI  - Amrubicin as second- or third-line treatment for women with metastatic HER2
      negative breast cancer: a Sarah Cannon Research Institute phase 1/2 trial.
AB  - Amrubicin is a synthetic anthracycline which has been shown in preclinical
      studies to have broad-spectrum anti-tumor activity and a lower potential for
      cardiotoxicity as compared to doxorubicin. We conducted a phase 1/2 trial of
      single-agent amrubicin as second- or third-line treatment for women with
      metastatic breast cancer. Women with metastatic HER2-negative breast cancer who
      had normal cardiac function and measurable disease, received intravenous (IV)
      amrubicin every 3 weeks. Prophylactic treatment with granulocyte colony
      stimulating factors (G-CSFs) was recommended. Escalating amrubicin doses were
      administered in a 3 + 3 design in the phase 1 portion to determine the maximum
      tolerated dose. Achievement of a median PFS >=4.5 months would warrant further
      development of amrubicin in this setting. Seventy-eight women (median age 58
      years) were treated (phase 1, 15 patients; phase 2, 63 patients). An amrubicin
      dose of 110 mg/m(2) every 3 weeks was selected as the phase 2 dose, and 66
      patients were treated. Twelve of 66 patients (18%) achieved objective response,
      and the clinical benefit rate was 42%. Median PFS was 4 months (95% CI 2.5, 5.8).
      Neutropenia was the most common grade 3/4 toxicity, observed in 29 patients
      (44%). One patient experienced an asymptomatic transient left ventricular
      ejection fraction decline (grade 3). Although the study did not meet the
      predefined PFS, amrubicin was well tolerated at 110 mg/m(2) IV when administered
      every 3 weeks with prophylactic G-CSF, and was an active second- or third-line
      treatment for metastatic HER2-negative breast cancer.

PMID- 25374099
TI  - Considerations of private sector obstetricians on participation in the state led
      "Chiranjeevi Yojana" scheme to promote institutional delivery in Gujarat, India:
      a qualitative study.
AB  - BACKGROUND: In India a lack of access to emergency obstetric care contributes to
      maternal deaths. In 2005 Gujarat state launched a public-private partnership
      (PPP) programme, Chiranjeevi Yojana (CY), under which the state pays accredited
      private obstetricians a fixed fee for providing free intrapartum care to poor and
      tribal women. A million women have delivered under CY so far. The participation
      of private obstetricians in the partnership is central to the programme's
      effectiveness. We explored with private obstetricians the reasons and experiences
      that influenced their decisions to participate in the CY programme. METHOD: In
      this qualitative study we interviewed 24 purposefully selected private
      obstetricians in Gujarat. We explored their views on the scheme, the reasons and
      experiences leading up to decisions to participate, not participate or withdraw
      from the CY, as well as their opinions about the scheme's impact. We analysed
      data using the Framework approach. RESULTS: Participants expressed a tension
      between doing public good and making a profit. Bureaucratic procedures and
      perceptions of programme misuse seemed to influence providers to withdraw from
      the programme or not participate at all. Providers feared that participating in
      CY would lower the status of their practices and some were deterred by the
      likelihood of more clinically difficult cases among eligible CY beneficiaries.
      Some providers resented taking on what they saw as a state responsibility to
      provide safe maternity services to poor women. Younger obstetricians in the
      process of establishing private practices, and those in more remote, 'less
      competitive' areas, were more willing to participate in CY. Some doctors had
      reservations over the quality of care that doctors could provide given the
      financial constraints of the scheme. CONCLUSIONS: While some private
      obstetricians willingly participate in CY and are satisfied with its functioning,
      a larger number shared concerns about participation. Operational difficulties and
      a trust deficit between the public and private health sectors affect retention of
      private providers in the scheme. Further refinement of the scheme, in
      consultation with private partners, and trust building initiatives could
      strengthen the programme. These findings offer lessons to those developing public
      private partnerships to widen access to health services for underprivileged
      groups.

PMID- 25374100
TI  - Effects of amyloid and small vessel disease on white matter network disruption.
AB  - There is growing evidence that the human brain is a large scale complex network.
      The structural network is reported to be disrupted in cognitively impaired
      patients. However, there have been few studies evaluating the effects of amyloid
      and small vessel disease (SVD) markers, the common causes of cognitive
      impairment, on structural networks. Thus, we evaluated the association between
      amyloid and SVD burdens and structural networks using diffusion tensor imaging
      (DTI). Furthermore, we determined if network parameters predict cognitive
      impairments. Graph theoretical analysis was applied to DTI data from 232
      cognitively impaired patients with varying degrees of amyloid and SVD burdens.
      All patients underwent Pittsburgh compound-B (PiB) PET to detect amyloid burden,
      MRI to detect markers of SVD, including the volume of white matter
      hyperintensities and the number of lacunes, and detailed neuropsychological
      testing. The whole-brain network was assessed by network parameters of
      integration (shortest path length, global efficiency) and segregation (clustering
      coefficient, transitivity, modularity). PiB retention ratio was not associated
      with any white matter network parameters. Greater white matter hyperintensity
      volumes or lacunae numbers were significantly associated with decreased network
      integration (increased shortest path length, decreased global efficiency) and
      increased network segregation (increased clustering coefficient, increased
      transitivity, increased modularity). Decreased network integration or increased
      network segregation were associated with poor performances in attention,
      language, visuospatial, memory, and frontal-executive functions. Our results
      suggest that SVD alters white matter network integration and segregation, which
      further predicts cognitive dysfunction. 

PMID- 25374102
TI  - Diffusion tensor imaging correlates of cognitive-motor decline in normal aging
      and increased Alzheimer's disease risk.
AB  - Alzheimer's disease (AD) is typically associated with impairments in memory and
      other aspects of cognition, while deficits in complex movements are commonly
      observed later in the course of the disease. Recent studies, however, have
      indicated that subtle deteriorations in visuomotor control under cognitively
      demanding conditions may in fact be an early identifying feature of AD. Our
      previous work has shown that the ability to perform visuomotor tasks that rely on
      visual-spatial and rule-based transformations is disrupted in prodromal and
      preclinical AD. Here, in a sample of 30 female participants (10 young: mean age =
      26.6 +/- 2.7, 10 low AD risk: mean age = 58.7 +/- 5.6, and 10 high AD risk: mean
      age = 58.5 +/- 6.9), we test the hypothesis that these cognitive-motor
      impairments are associated with early AD-related brain alterations. Using
      diffusion-weighted magnetic resonance imaging, we examined changes in white
      matter (WM) integrity associated with normal aging and increased AD risk, and
      assessed the relationship between these underlying WM alterations and cognitive
      motor performance. Our whole-brain analysis revealed significant age-related
      declines in WM integrity, which were more widespread in high relative to low AD
      risk participants. Furthermore, analysis of mean diffusivity measures within
      isolated WM clusters revealed a stepwise decline in WM integrity across young,
      low AD risk, and high AD risk groups. In support of our hypothesis, we also
      observed that lower WM integrity was associated with poorer cognitive-motor
      performance. These results are the first to demonstrate a relationship between AD
      related WM alterations and impaired cognitive-motor control. The application of
      these findings may provide a novel clinical strategy for the early detection of
      individuals at increased AD risk. 

PMID- 25374101
TI  - Long-acting intranasal insulin detemir improves cognition for adults with mild
      cognitive impairment or early-stage Alzheimer's disease dementia.
AB  - Previous trials have shown promising effects of intranasally administered insulin
      for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive
      impairment (MCI). These trials used regular insulin, which has a shorter half
      life compared to long-lasting insulin analogues such as insulin detemir. The
      current trial examined whether intranasal insulin detemir improves cognition or
      daily functioning for adults with MCI or AD. Sixty adults diagnosed with MCI or
      mild to moderate AD received placebo (n = 20), 20 IU of insulin detemir (n = 21),
      or 40 IU of insulin detemir (n = 19) for 21 days, administered with a nasal drug
      delivery device. Results revealed a treatment effect for the memory composite for
      the 40 IU group compared with placebo (p < 0.05). This effect was moderated by
      APOE status (p < 0.05), reflecting improvement for APOE-epsilon4 carriers (p <
      0.02), and worsening for non-carriers (p < 0.02). Higher insulin resistance at
      baseline predicted greater improvement with the 40 IU dose (r = 0.54, p < 0.02).
      Significant treatment effects were also apparent for verbal working memory (p <
      0.03) and visuospatial working memory (p < 0.04), reflecting improvement for
      subjects who received the high dose of intranasal insulin detemir. No significant
      differences were found for daily functioning or executive functioning. In
      conclusion, daily treatment with 40 IU insulin detemir modulated cognition for
      adults with AD or MCI, with APOE-related differences in treatment response for
      the primary memory composite. Future research is needed to examine the
      mechanistic basis of APOE-related treatment differences, and to further assess
      the efficacy and safety of intranasal insulin detemir. 

PMID- 25374103
TI  - Carboxy terminus heat shock protein 70 interacting protein reduces tau-associated
      degenerative changes.
AB  - One of the hallmarks of Alzheimer's disease is the formation of neurofibrillary
      tangles, intracellular aggregates of hyperphosphorylated, mislocalized tau
      protein, which are associated with neuronal loss. Changes in tau are known to
      impair cellular transport (including that of mitochondria) and are associated
      with cell death in cell culture and mouse models of tauopathy. Thus clearing
      pathological forms of tau from cells is a key therapeutic strategy. One critical
      modulator in the degradation and clearance of misfolded proteins is the co
      chaperone CHIP (Carboxy terminus Hsp70 interacting Protein), which is known to
      play a role in refolding and clearance of hyperphosphorylated tau. Here, we
      tested the hypothesis that CHIP could ameliorate pathological changes associated
      with tau. We find that co-expressing CHIP with full-length tau, tau truncated at
      D421 mimicking caspase cleavage, or the short tauRDDeltaK280 tau construct
      containing only the tau repeat domain with a tauopathy mutation, decreases tau
      protein levels in human H4 neuroglioma cells in a manner dependent on the Hsp70
      binding TPR domain of CHIP. The observed reduction in tau levels by CHIP is
      associated with a decrease of tau phosphorylation and reduced levels of cleaved
      Caspase 3 indicating that CHIP plays an important role in preventing tau-induced
      pathological changes. Furthermore, tau-associated mitochondrial transport
      deficits are rescued by CHIP co-expression in H4 cells. Together, these data
      suggest that the co-chaperone CHIP can rescue the pathological effects of tau,
      and indicate that other diseases of protein misfolding and accumulation may also
      benefit from CHIP upregulation. 

PMID- 25374104
TI  - Can we do better? Researchers' experiences with ethical review boards on projects
      with later life as a focus.
AB  - The goal of this study was to describe researchers' experiences in submitting
      ethical proposals focused on older adult populations, including studies with
      persons with dementia, to ethical review boards. Ethical approval was granted for
      an online survey. Researchers were recruited via listservs and snowballing
      techniques. Participants included 157 persons (73% female) from Australia and the
      United States, with a mean age of 46 (+/-13). Six main issues were encountered by
      researchers who participated in this survey. In descending order, these included
      questions regarding: informed consent and information requirements (61.1%),
      participants' vulnerability, particularly for those with cognitive impairments
      (58.6%), participant burden (44.6%), data access (29.3%), adverse effects of data
      collection/intervention (26.8%), and study methodology (25.5%). An inductive
      content analysis of responses revealed a range of encounters with ethical review
      panels spanning positive, negative, and neutral experiences. Concerns voiced
      about ethical review boards included committees being overly focused on legal
      risk, as well as not always hearing the voice of older research participants,
      both potential and actual. Respondents noted inability to move forward on
      studies, as well as loss of researchers and participant groups from
      gerontological and clinical research as a result of negative interactions with
      ethics committees. Positive interactions with the committees reinforced
      researchers' need to carefully construct their research approaches with persons
      with dementia in particular. Suggested guidelines for committees when dealing
      with ethics applications involving older adults include self-reflecting on
      potential biases and stereotypes, and seeking further clarification and
      information from gerontological researchers before arriving at decisions. 

PMID- 25374105
TI  - Shorter adult height is associated with poorer cognitive performance in elderly
      men with type II diabetes.
AB  - We studied the relationship of adult body height with five cognitive outcomes
      (executive functioning, semantic categorization, attention/working memory,
      episodic memory, and an overall cognition measure) in 897 cognitively normal
      elderly with type 2 diabetes. Regression analyses controlling for
      sociodemographic, cardiovascular, and diabetes-related risk factors and
      depression demonstrated that in males, shorter stature was associated with poorer
      executive functioning (p = 0.001), attention/working memory (p = 0.007), and
      overall cognition (p = 0.016), but not with episodic memory (p = 0.715) or
      semantic categorization (p = 0.948). No relationship between height and cognition
      was found for females. In cognitively normal type 2 diabetes male subjects,
      shorter stature, a surrogate for early-life stress and poor nutrition, was
      associated with cognitive functions. 

PMID- 25374106
TI  - Altered neurotransmission prior to cognitive decline in AbetaPP/PS1 mice, a model
      of Alzheimer's disease.
AB  - Indirect evidence supports altered glutamate signaling with Alzheimer's disease,
      however, it is not known if glutamate neurotransmission is impacted prior to
      cognitive decline. We examined cognition and glutamate neurotransmission in 2-4
      month AbetaPP/PS1, an Alzheimer's disease model, and age-matched control mice.
      There were no differences in learning and memory as assessed by Morris water
      maze. However, in vivo electrochemical measures of potassium-evoked glutamate
      release in the CA1, but not the CA3 or dentate, was significantly elevated in
      AbetaPP/PS1 mice. These data support changes in the glutamatergic system that
      precedes cognitive decline in a mouse model of Alzheimer's disease. 

PMID- 25374107
TI  - Bone marrow-derived macrophages from AbetaPP/PS1 mice are sensitized to the
      effects of inflammatory stimuli.
AB  - Macrophages are key cells in tissue defense in the periphery and, under certain
      circumstances, infiltrate the central nervous system, where they may play a
      similar role in the brain, perhaps supporting the function of microglia.
      Macrophages have been shown to adopt different activation states in response to
      various stimuli. Specifically, when exposed to inflammatory stimuli such as
      interferon (IFN)gamma, the cells adopt the M1 phenotype, whereas when exposed to
      anti-inflammatory cytokines such as interleukin (IL)-4 or IL-13, the M2 phenotype
      is adopted. While M1 macrophages are associated with tissue defense and
      destruction of invading pathogens, M2 macrophages are involved in tissue repair
      and in terminating inflammation. It is well known that an inflammatory
      microenvironment exists in the brain of aged animals and also in the brain of
      mice that overexpress amyloid-beta protein precursor (AbetaPP) and presenilin 1
      (PS1; AbetaPP/PS1 mice), a commonly-used model of Alzheimer's disease (AD).
      Recent studies have revealed that immune cells, including macrophages, infiltrate
      the brain in both circumstances raising the possibility that these cells adopt
      the M1 activation state and contribute to the already-existing neuroinflammation.
      We set out to examine the responses of bone marrow-derived macrophages prepared
      from wildtype and AbetaPP/PS1 mice and demonstrate that cells from AbetaPP/PS1
      mice, even after several days in culture, respond more profoundly to IFNgamma
      than those from wildtype mice. We suggest that this propensity to respond to M1
      polarizing stimuli, together with the described changes in the brain of
      AbetaPP/PS1 mice, contribute to the development of chronic neuroinflammation. 

PMID- 25374108
TI  - Dexmedetomidine directly increases tau phosphorylation.
AB  - Exposure to anesthetic agents has been linked to abnormal tau protein
      phosphorylation, an antecedent to the development of neurofibrillary tangles.
      This study evaluates the direct and indirect effects of dexmedetomidine. Primary
      culture of cortical neurons established from Sprague-Dawley (SD) rat embryos were
      exposed to dexmedetomidine for 1 or 6 hours, and the degree of tau
      phosphorylation at the AT8, AT180, and S396 sites was assessed by western blot
      analysis. To assess and compare their relative in vivo effects, the same agent
      was administered intravenously to 8 to 10 week old male SD rats and titrated to
      the loss of the righting reflex for 2 hours. After 1 hour of recovery, the rats
      were sacrificed and samples taken from the cortex and hippocampus were subjected
      to western blot and immunohistochemical analysis. The in vitro studies reviewed
      significant hyperphosphorylation only at the S396 site, and these changes have
      largely disappeared at 6 hours. With temperature maintenance, dexmedetomidine
      induced significant changes in hyperphosphorylation at the AT8 site in the cortex
      and hippocampus and at the AT180 in the hippocampus. The direct effect of
      anesthetic agents on fully differentiated cortical neurons is epitope-specific
      and short-lived. The in vivo effects are comparatively more complicated and
      depend not only on the phosphorylation site but the regions of the brain
      examined. These findings suggest that dexmedetomidine increases tau
      phosphorylation both in vitro and in vivo under normothermic conditions, and
      further studies are warranted to determine the long-term impact of this
      anesthetic on the tau pathology and even cognitive function. 

PMID- 25374109
TI  - Risk factors of caregiver burden among patients with Alzheimer's disease or
      related disorders: a cross-sectional study.
AB  - BACKGROUND: Caregivers play a major role in the care of patients with dementia
      and are themselves at higher risk of disease. OBJECTIVES: We investigate which
      factors are associated with caregivers burden of outpatients visiting a memory
      clinic and how functional autonomy and behavioral and psychological symptoms can
      influence caregiver burden. METHODS: The study population was chosen from
      outpatients with progressive cognitive complaint. The caregiver burden was
      measured with the short version of the Zarit Burden Interview (ZBI). The
      relationship was assessed between the ZBI and the patients characteristics,
      including Neuropsychiatric Inventory (NPI), Instrumental Activities of Daily
      Living scale (IADL), the Mini-Mental State Examination (MMSE), etiology, and
      stage of the cognitive impairment. RESULTS: In a population of 548 patients,
      IADL, NPI, antidepressant drugs, and MMSE were found to be related to ZBI, while
      diagnosed etiology and disease stage were not significant: ZBI decreased by 0.34
      point for every unit of IADL, and by 0.03 point for every unit of MMSE; ZBI
      increased by 0.03 point for every unit of NPI. From the IADL scale, the ability
      to handle finances, food preparation, responsibility to take medications, mode of
      transportation, and ability to use the telephone increased the ZBI. Five areas of
      the NPI increased the ZBI: apathy, agitation, aberrant motor behavior, appetite
      disorders (p < 0.001), and irritability (p = 0.03). CONCLUSION: Caregivers
      experience a higher burden due to disease symptoms such as impairment of
      functional autonomy and behavioral and cognitive impairment, whatever the
      etiology of the cognitive decline.

PMID- 25374110
TI  - Peripheral biomarkers of Alzheimer's disease.
AB  - Currently available diagnostic tests have moved the field closer to early
      diagnosis of Alzheimer's disease (AD); however, a definitive diagnosis is made
      only with the development of clinical dementia and the presence of amyloid
      plaques and neurofibrillary tangles at autopsy. An ideal antemortem AD biomarker
      should satisfy the following criteria: the ability to diagnose AD with high
      sensitivity and specificity as confirmed by the gold standard of autopsy
      validation; the ability to detect early-stage disease and track the progression
      of AD; and monitor therapeutic efficacy. AD biomarker technologies currently
      under development include in vivo brain imaging with PET and MRI (i.e., imaging
      of amyloid plaques, biochemical assays in cerebrospinal fluid (CSF) and
      peripheral tissues. CSF biomarkers have received increased attention in the past
      decade. However, it is unclear whether these biomarkers are capable of early
      diagnosis of AD, prior to Abeta accumulation, or whether they can differentiate
      between AD and non-AD dementias. In addition, CSF biomarkers may not lend
      themselves to diagnostic screening of elderly patients, given the invasiveness of
      lumbar puncture, inter-laboratory variability in techniques and sample handling,
      and the circadian fluctuation of CSF components. Although commonly viewed as an
      abnormality of the brain, AD is a systemic disease with associated dysfunction in
      metabolic, oxidative, inflammatory, and biochemical pathways in peripheral
      tissues, such as the skin and blood cells. This has led researchers to
      investigate and develop assays of peripheral AD biomarkers (a few with high
      sensitivity and specificity) that require minimally invasive skin or blood
      samples. 

PMID- 25374111
TI  - Comparison of new adenosine diphosphate receptor antagonists with clopidogrel in
      patients with coronary artery disease: a meta-analysis.
AB  - Recent data suggest the superiority of new adenosine diphosphate (ADP) receptor
      antagonists compared with clopidogrel in acute coronary syndrome patients. We
      aimed to assess the risks and benefits of new ADP receptor antagonists in
      patients with coronary artery disease (CAD). Relevant studies published through
      February 28, 2014 were searched and identified in the MEDLINE, EMBASE, and
      Cochrane databases. Summary estimates were obtained using a random-effects model.
      All nine published randomized controlled studies comparing new ADP receptor
      antagonists with clopidogrel in CAD were included. The database consisted of
      66,900 patients; 33,782 on novel agents, and 33,118 on clopidogrel. New ADP
      receptor antagonists reduced the composite incidence of all-cause mortality,
      myocardial infarction or stroke (odds ratio [OR] 0.89, 95 % confidence interval
      [CI] 0.81-0.97, p = 0.01) but increased the incidence of non-coronary artery
      bypass grafting-related major bleeding (OR 1.24, 95 % CI 1.08-1.42, p = 0.003).
      The composite end point of the net rate of adverse clinical events, which was the
      combination of the primary efficacy end point and the primary safety end point,
      was significantly lower in the new agent group compared to the clopidogrel group
      (9.7 versus 10.6 %, OR 0.92, 95 % CI 0.85-1.00). Use of recently introduced new
      ADP receptor antagonists results in a reduction in adverse clinical outcomes but
      a substantial increase in bleeding. New agents revealed an improved combined
      efficacy and safety outcome compared to that of clopidogrel in patients with CAD.

PMID- 25374112
TI  - Accuracy of specimen-specific nonlinear finite element analysis for evaluation of
      radial diaphysis strength in cadaver material.
AB  - The feasibility of a user-specific finite element model for predicting the in
      situ strength of the radius after implantation of bone plates for open fracture
      reduction was established. The effect of metal artifact in CT imaging was
      characterized. The results were verified against biomechanical test data.
      Fourteen cadaveric radii were divided into two groups: (1) intact radii for
      evaluating the accuracy of radial diaphysis strength predictions with finite
      element analysis and (2) radii with a locking plate affixed for evaluating metal
      artifact. All bones were imaged with CT. In the plated group, radii were first
      imaged with the plates affixed (for simulating digital plate removal). They were
      then subsequently imaged with the locking plates and screws removed (actual plate
      removal). Fracture strength of the radius diaphysis under axial compression was
      predicted with a three-dimensional, specimen-specific, nonlinear finite element
      analysis for both the intact and plated bones (bones with and without the plate
      captured in the scan). Specimens were then loaded to failure using a universal
      testing machine to verify the actual fracture load. In the intact group, the
      physical and predicted fracture loads were strongly correlated. For radii with
      plates affixed, the physical and predicted (simulated plate removal and actual
      plate removal) fracture loads were strongly correlated. This study demonstrates
      that our specimen-specific finite element analysis can accurately predict the
      strength of the radial diaphysis. The metal artifact from CT imaging was shown to
      produce an overestimate of strength. 

PMID- 25374113
TI  - Pigment cell interactions and differential xanthophore recruitment underlying
      zebrafish stripe reiteration and Danio pattern evolution.
AB  - Fishes have diverse pigment patterns, yet mechanisms of pattern evolution remain
      poorly understood. In zebrafish, Danio rerio, pigment-cell autonomous
      interactions generate dark stripes of melanophores that alternate with light
      interstripes of xanthophores and iridophores. Here, we identify mechanisms
      underlying the evolution of a uniform pattern in D. albolineatus in which all
      three pigment cell classes are intermingled. We show that in this species
      xanthophores differentiate precociously over a wider area, and that cis
      regulatory evolution has increased expression of xanthogenic Colony Stimulating
      Factor-1 (Csf1). Expressing Csf1 similarly in D. rerio has cascading effects,
      driving the intermingling of all three pigment cell classes and resulting in the
      loss of stripes, as in D. albolineatus. Our results identify novel mechanisms of
      pattern development and illustrate how pattern diversity can be generated when a
      core network of pigment-cell autonomous interactions is coupled with changes in
      pigment cell differentiation. 

PMID- 25374114
TI  - A select review reporting the quality of studies measuring endothelial
      dysfunction in randomised diet intervention trials.
AB  - A quality assessment of the primary studies reported in the literature carried
      out using select dietary ingredients (DI) purported to affect vascular
      endothelial function was conducted through a systematic PubMed search from
      January 2000 to August 2012. A total of seventy randomised controlled trials with
      defined DI (folic acid (fifteen), n-3 fatty acids (twenty), cocoa (fifteen) and
      isoflavones (twenty)) and standardised measures of vascular endothelial function
      were evaluated. Jadad scores, quality scoring parameters for DI and flow-mediated
      dilation (FMD) methodology used were ascertained. A total of 3959 randomised
      subjects, mean age 51 (se 0.21) years (range 9-79 years), were represented in the
      dataset. The mean Jadad scores did not differ statistically among the DI studies,
      with the majority of the studies being of good quality. Higher DI quality scores
      were achieved by studies using the botanical ingredients cocoa and isoflavones
      than by those using the nutrient ingredients folic acid and n-3 fatty acids. The
      mean DI quality scores were 4.13 (se 0.34), 5.20 (se 0.47), 6.13 (se 0.41) and
      6.00 (se 0.59) for the folic acid, n-3 fatty acid, cocoa and isoflavone
      intervention studies, respectively (and significantly different). The mean
      Corretti FMD scores were 7.27 (se 0.56), 7.46 (se 0.79), 6.29 (se 0.61) and 7.11
      (se 0.56) for the folic acid, n-3 fatty acid, cocoa and isoflavone intervention
      studies, respectively (NS). FMD studies failed to adequately describe the
      equipment used and more than half failed to provide an adequate description of
      the procedures used for vascular image acquisition and measurement. DI can be
      utilised for dietary intervention studies; however, the methodology should be
      clearly reported using the guidelines for assessment for both DI and FMD. 

PMID- 25374116
TI  - [Fumaric acid or dimethyl fumarate?].

PMID- 25374115
TI  - Exploring the correlation between the sequence composition of the nucleotide
      binding G5 loop of the FeoB GTPase domain (NFeoB) and intrinsic rate of GDP
      release.
AB  - GDP release from GTPases is usually extremely slow and is in general assisted by
      external factors, such as association with guanine exchange factors or membrane
      embedded GPCRs (G protein-coupled receptors), which accelerate the release of GDP
      by several orders of magnitude. Intrinsic factors can also play a significant
      role; a single amino acid substitution in one of the guanine nucleotide
      recognition motifs, G5, results in a drastically altered GDP release rate,
      indicating that the sequence composition of this motif plays an important role in
      spontaneous GDP release. In the present study, we used the GTPase domain from
      EcNFeoB (Escherichia coli FeoB) as a model and applied biochemical and structural
      approaches to evaluate the role of all the individual residues in the G5 loop.
      Our study confirms that several of the residues in the G5 motif have an important
      role in the intrinsic affinity and release of GDP. In particular, a T151A mutant
      (third residue of the G5 loop) leads to a reduced nucleotide affinity and
      provokes a drastically accelerated dissociation of GDP. 

PMID- 25374118
TI  - Growth and structure of ultrathin alumina films on the (1 1 0) surface of gamma
      Al4Cu9 complex metallic alloy.
AB  - The first stages of oxidation of the (1 1 0) surface of a gamma-Al(4)Cu(9)
      complex metallic alloy were investigated by combining x-ray photoemission
      spectroscopy, low energy electron diffraction and scanning tunnel microscopy
      studies. Oxidation at room temperature in the 2 * 10(-8) to 2 * 10(-7) mbar
      oxygen pressure range occurs in two steps: a fast regime is followed by a much
      slower one, leading to the formation of a thin aluminium oxide film showing no
      long range order. Cu-O bonds are never observed, due to fast oxygen induced
      aluminium segregation. The low value of the estimated activation energy for
      aluminium diffusion (0.65 +/- 0.12 eV at(-1)) was ascribed to the presence of two
      vacancies in the gamma-Al(4)Cu(9) structure. Annealing at 925 K the oxide film
      formed at room temperature leads to the formation of small crystallized domains
      with a sixton structure similar to structures reported in the literature
      following the oxidation of Cu-9% Al(1 1 1), NiAl (1 1 0) and FeAl(1 1 0) surfaces
      as well as ultrathin Al films deposited onto Cu(1 1 1) or Ni(1 1 1) surfaces. Two
      contributions were observed in the O1s peaks, which have been ascribed to loosely
      bound oxygen species and oxygen belonging to the sixton structure respectively.

PMID- 25374117
TI  - Synthesis and biological evaluation of QRSTUVWXYZA' domains of maitotoxin.
AB  - The synthesis of QRSTUVWXYZA' domains 7, 8, and 9 of the highly potent marine
      neurotoxin maitotoxin (1), the largest secondary metabolite isolated to date, is
      described. The devised synthetic strategy entailed a cascade Takai-Utimoto ester
      olefination/ring closing metathesis to construct ring Y, a hydroxydithioketal
      cyclization/methylation sequence to cast ring X, a Horner-Wadsworth-Emmons
      coupling of WXYZA' ketophosphonate 11 with QRSTU aldehyde 12 to form enone 10,
      and a reductive hydroxyketone ring closure to forge ring V. 2D NMR spectroscopic
      analysis and comparison of (13)C chemical shifts with those of the corresponding
      carbons of maitotoxin revealed close similarities supporting the originally
      assigned structure of this region of the natural product. Biological evaluations
      of various synthesized domains of maitotoxin in this and previous studies from
      these laboratories led to fragment structure-activity relationships regarding
      their ability to inhibit maitotoxin-elicited Ca(2+) influx in rat C6 glioma
      cells. 

PMID- 25374120
TI  - Piezoelectric coupling in a field-effect transistor with a nanohybrid channel of
      ZnO nanorods grown vertically on graphene.
AB  - Piezoelectric coupling phenomena in a graphene field-effect transistor (GFET)
      with a nano-hybrid channel of chemical-vapor-deposited Gr (CVD Gr) and vertically
      aligned ZnO nanorods (NRs) under mechanical pressurization were investigated.
      Transfer characteristics of the hybrid channel GFET clearly indicated that the
      piezoelectric effect of ZnO NRs under static or dynamic pressure modulated the
      channel conductivity (sigma) and caused a positive shift of 0.25% per kPa in the
      Dirac point. However, the GFET without ZnO NRs showed no change in either sigma
      or the Dirac point. Analysis of the Dirac point shifts indicated transfer of
      electrons from the CVD Gr to ZnO NRs due to modulation of their interfacial
      barrier height under pressure. High responsiveness of the hybrid channel device
      with fast response and recovery times was evident in the time-dependent behavior
      at a small gate bias. In addition, the hybrid channel FET could be gated by
      mechanical pressurization only. Therefore, a piezoelectric-coupled hybrid channel
      GFET can be used as a pressure-sensing device with low power consumption and a
      fast response time. Hybridization of piezoelectric 1D nanomaterials with a 2D
      semiconducting channel in FETs enables a new design for future nanodevices. 

PMID- 25374119
TI  - Simvastatin attenuates angiotensin II-induced inflammation and oxidative stress
      in human mesangial cells.
AB  - Chronic kidney disease (CKD) is an intractable disease in which inflammation and
      oxidative stress are important. In the present study, the effect of simvastatin
      on inflammation and oxidative stress induced by angiotensin II (Ang II) in human
      mesangial cells (HMCs) and its corresponding mechanism was examined. In the in
      vitro experiment, HMCs were pretreated either without additives (control group)
      or with simvastatin at different concentrations (0, 0.1, 1 or 10 uM) for 1 h and
      were then stimulated by Ang II (1 uM) for 24 h. Following stimulation, the cells
      were collected for analysis using quantitative polymerase chain reaction, western
      blotting and dihydroethidium staining. The supernatant of the cells was collected
      and analyzed using an enzyme-linked immunosorbent assay. The results demonstrated
      that simvastatin suppressed the increased mRNA expression of monocyte
      chemoattractant protein-1, tumor necrosis factor-alpha, interleukin (IL)-1beta
      and IL-6 and the content of reactive oxygen species induced by Ang II in a dose
      dependent manner. In addition, simvastatin decreased the protein expression of
      cyclooxygenase-2 (COX-2), nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase and protein kinase C (PKC) as well as the content of prostaglandin E2 and
      the phosphorylation level of nuclear factor-kappaB (NF-kappaB) p65 in a dose
      dependent manner. Furthermore, simvastatin significantly increased the protein
      expression of peroxisome proliferator-activated receptor gamma (PPARgamma).
      Therefore, simvastatin suppressed inflammation and oxidative stress in Ang II
      stimulated HMCs via COX-2, PPARgamma, NF-kappaB, NADPH oxidase and PKCs, thereby
      exerting a protective effect on CKD.

PMID- 25374122
TI  - The principle of equipoise in pediatric drug trials.
AB  - Equipoise is a fundamental ethical principle in the conduct of interventional
      trials comparing two or more treatment arms. This principle dictates that, at the
      time of planning and executing such trials, the researchers must have no
      compelling evidence that one arm is superior to the other arm(s). That means that
      it is unethical to involve patients in a study where one intervention is
      convincingly better than the other, as this would mean that a group of patients
      will receive an inferior option, which may endanger their health. While this
      principle may be straightforward at the beginning of a trial, there are numerous
      ways how it may be subsequently disrupted. Presently, most of the literature on
      equipoise deals with adult patients, with very little experience in children.
      This paper illustrates the principle of equipoise and the process of defining it.
      Because the majority of pediatric medications have not been studied adequately
      and are not labeled for pediatric use, it is often challenging to decide whether
      equipoise exists for a certain pharmacological treatment. Moreover, the equipoise
      may dynamically change during the conduct of a study, if new evidence from other
      studies becomes available. 

PMID- 25374123
TI  - In-depth analysis of site-specific N-glycosylation in vitronectin from human
      plasma by tandem mass spectrometry with immunoprecipitation.
AB  - The characterization of site-specific microheterogeneity in glycoprotein is very
      important for understanding cell biology and disease processes. Vitronectin is
      well known to be a multifunctional glycoprotein in the blood and the
      extracellular matrix, which is related to hepatocellular carcinoma (HCC). Here,
      we systematically analyzed the site-specific N-glycopeptides of vitronectin in
      human plasma by tandem mass spectrometry combined with immunoprecipitation and
      hydrophilic interaction liquid chromatography (HILIC) enrichment. Vitronectin was
      purified with immunoprecipitation by monoclonal antibody from plasma and digested
      to tryptic N-glycopeptides.Then, enrichment with HILIC materials was used and
      followed by analysis with nano-LC/MS/MS. The sequences of N-glycopeptides were
      identified from the mass spectra by high-energy C-trap dissociation (HCD) and
      collision-induced dissociation (CID). In HCD mode, oxonium ions were used for
      recognizing glycopeptides and y ions for sequencing the peptide backbone. In CID
      mode, Y ions were used for characterizing their glycoforms. As a result, a total
      of 17 site-specific N-glycopeptides were completely identified in all of the
      three N-glycosylation sites of vitronectin in human plasma, including 12 N
      glycopeptides first reported. Finally, we specifically found that three hybrid
      and four complex glycopeptides of triantennary forms with outer fucosylation
      increased in HCC human plasma. 

PMID- 25374124
TI  - A feasibility study of the use of saliva as an alternative to leukocytes as a
      source of DNA for the study of Pt-DNA adducts in cancer patients receiving
      platinum-based chemotherapy.
AB  - This note presents a comparison of the use of saliva versus leukocytes for the
      determination of Pt-DNA adducts obtained from patients undergoing platinum-based
      chemotherapy. Samples of both blood and saliva were taken pre- and post-treatment
      and were analysed via sector-field inductively coupled plasma mass spectrometry
      (SF-ICP-MS) to determine the level of Pt-DNA adducts formed. As expected,
      significant inter-patient variability was seen; however, a lack of correlation
      between the levels of adducts observed in saliva and blood samples was also
      observed (Pearson correlation coefficient r = -0.2598). A high yield of DNA was
      obtained from saliva samples, but significant difficulties were experienced in
      obtaining patient adherence to the saliva sampling procedure. In both leukocyte
      and saliva samples, not only was Pt from previous chemotherapy cycles detected,
      but the rapid appearance of Pt in the DNA was noted in both sample types 1 h
      after treatment. 

PMID- 25374125
TI  - Direct and mediated electrochemistry of peroxidase and its electrocatalysis on a
      variety of screen-printed carbon electrodes: amperometric hydrogen peroxide and
      phenols biosensor.
AB  - This study compares the behaviour of direct and mediated electrochemistry of
      horseradish peroxidase (HRP) immobilised on screen-printed carbon electrodes
      (SPCEs), screen-printed carbon electrodes modified with carboxyl-functionalised
      multi-wall carbon nanotubes (MWCNT-SPCEs) and screen-printed carbon electrodes
      modified with carboxyl-functionalised single-wall carbon nanotubes (SWCNT-SPCEs).
      The techniques of cyclic voltammetry and amperometry in the flow mode were used
      to characterise the properties of the HRP immobilised on screen-printed
      electrodes. From measurements of the mediated and mediatorless currents of
      hydrogen peroxide reduction at the HRP-modified electrodes, it was concluded that
      the fraction of enzyme molecules in direct electron transfer (DET) contact with
      the electrode varies substantially for the different electrodes. It was observed
      that the screen-printed carbon electrodes modified with carbon nanotubes (MWCNT
      SPCEs and SWCNT-SPCEs) demonstrated a substantially higher percentage (~100 %) of
      HRP molecules in DET contact than the screen-printed carbon electrodes (~60 %).
      The HRP-modified electrodes were used for determination of hydrogen peroxide in
      mediatorless mode. The SWCNT-SPCE gave the lowest detection limit (0.40 +/- 0.09
      MUM) followed by MWCNT-SPCE (0.48 +/- 0.07 MUM) and SPCE (0.98 +/- 0.2 MUM).
      These modified electrodes were additionally developed for amperometric
      determination of phenolic compounds. It was found that the SWCNT-SPCE gave a
      detection limit for catechol of 110.2 +/- 3.6 nM, dopamine of 640.2 +/- 9.2 nM,
      octopamine of 3341 +/- 15 nM, pyrogallol of 50.10 +/- 2.9 nM and 3,4-dihydroxy-L
      phenylalanine of 980.7 +/- 8.7 nM using 50 MUM H2O2 in the flow carrier. 

PMID- 25374126
TI  - Haematocrit corrected analysis of creatinine in dried blood spots through
      potassium measurement.
AB  - We developed a method for the analysis of creatinine in dried blood spot (DBS)
      samples to facilitate monitoring of renal function in combination with TDM of
      immunosuppressive drugs for transplant patients outside the hospital. An 8-mm
      disc of the DBS was punched, extracted and followed by LC-MS/MS analysis. The
      haematocrit proved to have a significant influence on the analysis of creatinine
      in DBS samples. As potassium is a suitable marker for haematocrit, we implemented
      a method for measuring potassium in DBS and correct the creatinine for
      haematocrit. For both creatinine and K(+) in DBS analytical and DBS, validation
      was performed, both components met the validation criteria and no other
      influences beside the haematocrit were detected. To assess the haematocrit
      correction, samples were compared to the 'golden' standard and plotted before and
      after correction. The correction showed a great improvement in agreement between
      the DBS assay and venous blood assay. 

PMID- 25374127
TI  - Cystic apocrine ductal carcinoma in situ with increased EGFR expression, trisomy
      7, and associated focal invasion.
AB  - A 71-year-old woman was admitted to our hospital with a lump in her right breast.
      Mammography revealed an internal high-density mass in the lower right breast,
      which was larger than it was 2 years ago. Considering the findings from
      ultrasonography, computed tomography, and cytology, an intracystic carcinoma
      could not be ruled out. The patient underwent excisional biopsy, which revealed
      an apocrine ductal carcinoma in situ (ADCIS) with focal invasive apocrine
      carcinoma (IAC). The diagnosis was based on morphology and immunohistochemistry
      (IHC), which was negative for the estrogen and progesterone receptors, and
      positive for the androgen receptor. Expression of the human epidermal growth
      factor receptor 2 and the epidermal growth factor receptor (EGFR) received an
      immunohistochemical score of 2+. Trisomy of chromosome 7, including multiple CEP
      7 and EGFR signals, was observed in ADCIS by fluorescence in situ hybridization
      (FISH). IAC exhibited similar results for IHC and FISH. This is the first
      reported case showing trisomy 7 resulting in EGFR copy number gain and increased
      EGFR expression in ADCIS. 

PMID- 25374128
TI  - Development of a novel fluorescence probe capable of assessing the cytoplasmic
      entry of siderophore-based conjugates.
AB  - A novel fluorescence probe capable of assessing the cytoplasmic entry of
      siderophore-based conjugates was synthesized and evaluated by photochemical
      characterization and cell-based assays. The specific responsiveness to the
      cytoplasmic entry of the probe was implemented by adopting a disulfide linker,
      whose cleavage under the reducing conditions of the cytoplasm induced the display
      of a distinctive fluorescence signal. 

PMID- 25374129
TI  - Piceatannol inhibits phorbol ester-induced expression of COX-2 and iNOS in HR-1
      hairless mouse skin by blocking the activation of NF-kappaB and AP-1.
AB  - OBJECTIVES: The present study was aimed at elucidating the molecular mechanisms
      of anti-inflammatory activity of piceatannol (trans-3,4,3',5'
      tetrahydroxystilbene) in mouse skin in vivo. METHODS: Female HR-1 hairless mice
      were topically treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) with or
      without piceatannol pretreatment. Epidermal protein expression was assessed by
      Western blot analysis. The cyclooxygenase-2 (COX-2) expression was detected by
      immunohistochemistry. The DNA binding of nuclear factor-kappaB (NF-kappaB) and
      activator protein-1 (AP-1) was examined by the electrophoretic mobility gel shift
      assay. The catalytic activity of IkappaBalpha kinase-beta (IKKbeta) was measured
      by in vitro kinase assay. RESULTS: Pretreatment with piceatannol attenuated TPA
      induced expression of COX-2 and inducible nitric oxide synthase (iNOS) in mouse
      skin. Piceatannol diminished nuclear translocation and the DNA binding of NF
      kappaB through the blockade of phosphorylation and subsequent degradation of
      IkappaBalpha. Piceatannol attenuated the catalytic activity of IKKbeta and
      inhibited the phosphorylation of mitogen-activated protein (MAP) kinases in TPA
      treated mouse skin. In addition, piceatannol decreased TPA-induced expression of
      c-Fos and the DNA binding of AP-1. CONCLUSION: Piceatannol inhibits TPA-induced
      COX-2 and iNOS expression by blocking the activation of NF-kappaB and AP-1 via
      suppression of the IKKbeta activity and phosphorylation of MAP kinases, which
      provides a mechanistic basis of its anti-inflammatory effects in mouse skin.

PMID- 25374130
TI  - Bone mineral density in treated at a young age for differentiated thyroid cancer
      after Chernobyl female patients on TSH-suppressive therapy receiving or not
      Calcium-D3 supplementation.
AB  - Long-term management of patients with differentiated thyroid cancer (DTC)
      commonly includes TSH-suppressive therapy with L-T4 and, in case of postsurgical
      hypoparathyroidism, Calcium-D3 supplementation, both of which may affect skeletal
      health. Experience with female patients treated for DTC at a young age and who
      were then receiving long-term therapy with L-T4 and Calcium-D3 medication is very
      limited to date. This cross-sectional study set out to investigate effects of
      Calcium-D3 supplementation and TSH-suppressive therapy on bone mineral density
      (BMD) in 124 young female patients treated for DTC at a mean age of 14 years and
      followed-up for an average of 10 years. BMD was found to be significantly higher
      in patients receiving Calcium-D3 medication than in patients not taking
      supplements. The level of ionized calcium was the strongest factor determining
      lumbar spine BMD in patients not receiving Calcium-D3 supplementation. Pregnancy
      ending in childbirth and HDL-cholesterol were associated with a weak adverse
      effect on spine and femoral BMD. No evidence of adverse effects of L-T4 and of
      radioiodine therapies on BMD was found. We conclude that Calcium-D3 medication
      has a beneficial effect on BMD, and that TSH-suppressive therapy does not affect
      BMD in women treated for DTC at young age, at least after 10 years of follow-up. 

PMID- 25374131
TI  - Impaired overt facial mimicry in response to dynamic facial expressions in high
      functioning autism spectrum disorders.
AB  - Previous electromyographic studies have reported that individuals with autism
      spectrum disorders (ASD) exhibited atypical patterns of facial muscle activity in
      response to facial expression stimuli. However, whether such activity is
      expressed in visible facial mimicry remains unknown. To investigate this issue,
      we videotaped facial responses in high-functioning individuals with ASD and
      controls to dynamic and static facial expressions of anger and happiness. Visual
      coding of facial muscle activity and the subjective impression ratings showed
      reduced congruent responses to dynamic expressions in the ASD group.
      Additionally, this decline was related to social dysfunction. These results
      suggest that impairment in overt facial mimicry in response to others' dynamic
      facial expressions may underlie difficulties in reciprocal social interaction
      among individuals with ASD. 

PMID- 25374132
TI  - Identifying the associated factors of mediation and due process in families of
      students with autism spectrum disorder.
AB  - Compared to families of students with other types of disabilities, families of
      students with autism spectrum disorder (ASD) are significantly more likely to
      enact their procedural safeguards such as mediation and due process. However, we
      do not know which school, child, and parent characteristics are associated with
      the enactment of safeguards. For this study, 507 parents of students with ASD
      responded to a national web-based survey. Parents who filed for due process or
      mediation were more likely to advocate for their child, have poor family-school
      partnerships, and have greater household incomes. Parents were also more likely
      to utilize their safeguards if their children were older, experiencing more
      internalizing behaviors, and educated in segregated placements. Implications for
      research and practice are discussed. 

PMID- 25374133
TI  - Detecting subgroups in children diagnosed with pervasive developmental disorder -
      not otherwise specified.
AB  - Hierarchical cluster analyses were used to detect three subgroups in a sample of
      children with pervasive developmental disorder--not otherwise specified (PDD-NOS)
      evaluated at ages 2 and 4. At age 2, Cluster 1 demonstrated few autism symptoms
      and high cognitive scores; 60% no longer met criteria for PDD at 4. Cluster 2
      exhibited more autism symptoms and lower cognitive scores at 2; 89.5% met
      criteria for ASD at 4. Cluster 3 had the lowest cognitive scores and most
      impaired social/communication skills at 2, but no repetitive behaviors; 60%
      diagnosed with Autistic Disorder at 4. Results shed light on outcomes for
      different PDD-NOS types and raise questions regarding the increased importance of
      repetitive behaviors in DSM-5.

PMID- 25374134
TI  - Prevalence of clinically and empirically defined talents and strengths in autism.
AB  - Outstanding skills, including special isolated skills (SIS) and perceptual peaks
      (PP) are frequent features of autism. However, their reported prevalence varies
      between studies and their co-occurrence is unknown. We determined the prevalence
      of SIS in a large group of 254 autistic individuals and searched for PP in 46 of
      these autistic individuals and 46 intelligence and age-matched typically
      developing controls. The prevalence of SIS among autistic individuals was 62.5%
      and that of PP was 58% (13% in controls). The prevalence of SIS increased with
      intelligence and age. The existence of an SIS in a particular modality was not
      associated with the presence of a PP in the same modality. This suggests that
      talents involve an experience-dependent component in addition to genetically
      defined alterations of perceptual encoding.

PMID- 25374135
TI  - Non-traumatic Dental Condition-Related Emergency Department Visits and Associated
      Costs for Children and Adults with Autism Spectrum Disorders.
AB  - We analyzed 2010 US National Emergency Department Sample data and ran regression
      models to test the hypotheses that individuals with ASD are more likely to have
      non-traumatic dental condition (NTDC)-related emergency department (ED) visits
      and to incur greater costs for these visits than those without ASD. There were
      nearly 2.3 million NTDC-related ED visits in 2010. Less than 1.0% (children) and
      2.1% (adults) of all ED visits were for NTDC. There was no significant difference
      in NTDC-related ED visits or costs for children by ASD status. Adults with ASD
      had significantly lower odds of NTDC-related ED visits (OR 0.39; 95% CI 0.29,
      0.52; p < 0.001) but incurred significantly greater mean costs for NTDC-related
      ED visits (p < 0.006) than did adults without ASD.

PMID- 25374137
TI  - A preliminary study of patients' perceptions on the implementation of the WHO
      surgical safety checklist in women who had Cesarean sections.
AB  - The surgical safety checklist (SSCL), developed by the World Health Organization,
      is widely implemented by surgical staff for the improvement of their
      communication, teamwork, and safety culture in the operating room. However, there
      is no research available addressing the question of how surgical patients
      perceive the implementation of the SSCL. In order to address this issue, a
      questionnaire-based preliminary study was conducted for patients who had
      undergone elective Cesarean section under awake regional anesthesia. Although
      most participants had not been informed about the implementation of the SSCL
      before surgery, all of the patients were aware that the SSCL had been performed
      in the operating room. Over 80% of patients answered that the implementation of
      the SSCL could help to reduce their feelings of anxiety, tension, and fear, as
      well as enhance their feeling of security. Furthermore, most patients answered
      that they were able to understand the components as well as the purpose of the
      SSCL, and considered that the SSCL should be implemented. These results suggest
      that awake patients undergoing Cesarean section perceive the implementation of
      the SSCL to be a highly positive aspect of their surgical care.

PMID- 25374136
TI  - Toward a Best-Practice Protocol for Assessment of Sensory Features in ASD.
AB  - Sensory difficulties are a commonly occurring feature of autism spectrum
      disorders and are now included as one manifestation of the 'restricted,
      repetitive patterns of behavior, interests, or activities' diagnostic criteria of
      the DSM5 necessitating guidelines for comprehensive assessment of these features.
      To facilitate the development of such guidelines, this paper provides an overview
      of the literature on sensory features in autism spectrum disorder. We summarize
      the literature pertaining to: terminology, current assessment practices, sensory
      development, and the relationship of sensory features to core symptoms of autism.
      The paper concludes with recommendations for clinical assessment of sensory
      features in Autism. 

PMID- 25374138
TI  - The effects of nicardipine or esmolol on the onset time of rocuronium and
      intubation conditions during rapid sequence induction: a randomized double-blind
      trial.
AB  - PURPOSE: The main aims of rapid sequence induction (RSI) are prompt and adequate
      muscle relaxation for tracheal intubation and hemodynamic stability during and
      after intubation. The purpose of the present study was to investigate the effects
      of nicardipine and esmolol on the action of rocuronium and intubation conditions
      during RSI. METHODS: Adult patients (n = 82) were randomly allocated to one of
      three groups. One minute prior to the induction of sevoflurane-based general
      anesthesia, patients received 20 MUg/kg of nicardipine (N group; n = 27) or 0.5
      mg/kg of esmolol (E group; n = 27), or 5 ml of saline (C group; n = 28). Patients
      were assessed according to intubation conditions, the onset time of rocuronium,
      mean arterial pressure (MAP), and heart rate (HR) during RSI. RESULTS: The
      intubation conditions and score were significantly better in the C and N groups
      than in the E group (P < 0.001). The onset time of rocuronium was shortened in
      the N group and prolonged in the E group when compared to the C group (P <
      0.001). A significant attenuation in the increase of MAP immediately after
      intubation was observed in the N group as compared with the C and E groups (P <
      0.008). HR was significantly lower in the E group than in the N and C groups (P <
      0.01). CONCLUSION: Pretreatment with nicardipine for RSI improved intubation
      conditions and shortened the onset time of rocuronium and attenuated changes in
      MAP after intubation. Esmolol may disturb intubation conditions and the onset of
      action of rocuronium, despite being effective in alleviating responses of HR
      after RSI.

PMID- 25374139
TI  - Cellulolytic enzymes production by utilizing agricultural wastes under solid
      state fermentation and its application for biohydrogen production.
AB  - Phanerochaete chrysosporium was evaluated for cellulase and hemicellulase
      production using various agricultural wastes under solid state fermentation.
      Optimization of various environmental factors, type of substrate, and medium
      composition was systematically investigated to maximize the production of enzyme
      complex. Using grass powder as a carbon substrate, maximum activities of
      endoglucanase (188.66 U/gds), exoglucanase (24.22 U/gds), cellobiase (244.60
      U/gds), filter paperase (FPU) (30.22 U/gds), glucoamylase (505.0 U/gds), and
      xylanase (427.0 U/gds) were produced under optimized conditions. The produced
      crude enzyme complex was employed for hydrolysis of untreated and mild acid
      pretreated rice husk. The maximum amount of reducing sugar released from enzyme
      treated rice husk was 485 mg/g of the substrate. Finally, the hydrolysates of
      rice husk were used for hydrogen production by Clostridium beijerinckii. The
      maximum cumulative H2 production and H2 yield were 237.97 mL and 2.93 mmoL H2/g
      of reducing sugar, (or 2.63 mmoL H2/g of cellulose), respectively. Biohydrogen
      production performance obtained from this work is better than most of the
      reported results from relevant studies. The present study revealed the cost
      effective process combining cellulolytic enzymes production under solid state
      fermentation (SSF) and the conversion of agro-industrial residues into renewable
      energy resources.

PMID- 25374140
TI  - Phenyl derivative of pyranocoumarin precludes Fusarium oxysporum f.sp.
      Lycopersici infection in Lycopersicon esculentum via induction of enzymes of the
      phenylpropanoid pathway.
AB  - Binding of phenyl derivative of pyranocoumarin (PDP) modulated activity of fungal
      endopolygalacturonase in silico. Induced fit docking study of PDP with
      endopolygalacturonase (1HG8) showed a bifurcated hydrogen bond interaction with
      the protein at Lys 244 with a docking score of -3.6 and glide energy of -37.30
      kcal/mol. Docking with endopolygalacturonase II (1CZF) resulted hydrogen bond
      formation with Lys 258 with a docking score of -2.3 and glide energy of -30.42
      kcal/mol. It was hypothesized that this modulation favors accumulation of cell
      wall fragments (oligogalacturonides) which act as elicitors of plant defense
      responses. In order to prove the same, in vivo studies were carried out using a
      formulation developed from PDP (PDP 5EC) on greenhouse grown Lycopersicon
      esculentum L. The formulation was effective at different concentrations in
      reduction of seed infection, improvement of vigor and control of Fusarium
      oxysporum f.sp. lycopersici infection in L. esculentum. At a concentration of 2
      %, PDP 5EC significant reduction in seed infection (95.83 %), improvement in seed
      vigor (64.31 %) and control of F. oxysporum f.sp. lycopersici infection (96.15 %)
      were observed. Further application of PDP 5EC to L. esculentum challenged with F.
      oxysporum f.sp. lycopersici significantly increased the activity of enzymes of
      the phenylpropanoid pathway, namely, peroxidase (PO), polyphenol oxidase (PPO),
      phenylalanine ammonia lyase (PAL), and enhanced the total phenolic content when
      compared to the control.

PMID- 25374141
TI  - Silica nanoparticles induced metabolic stress through EGR1, CCND, and E2F1 genes
      in human mesenchymal stem cells.
AB  - The SiO2 synthesized in bulk form, adopting the conventional methods for
      application in food industry applications, may also contain nano-sized particles.
      On account of the unique physico-chemical properties, the SiO2 particulates, such
      as size and shape, cause metabolic toxicity in cells. Poor understanding of the
      molecular level nanotoxicity resulting from high-volume synthetic SiO2 exposures
      in humans is a serious issue, since these particles may also contribute to
      metabolic stress-mediated chronic diseases. In the present study, we examined the
      structural characteristics of these nano-sized silica particles adopting SEM and
      dynamic light scattering (DLS) and assessed the alterations in the cell cycle
      induced by these silica particles in human mesenchymal stem cells (hMSCs)
      adopting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell
      viability assay, morphological changes in the cells adopting fluorescent
      microscopy, cell cycle analysis adopting flow cytometry, and the expression of
      genes linked to cell cycle (i.e., proliferating cell nuclear antigen (PCNA),
      early growth response protein (EGR1), E2F transcription factor (E2F1), cyclin D1,
      cyclin C, and cyclin D3) adopting qPCR. The SEM and DLS studies indicated that
      the commercial grade SiO2-NPs were in the nano-scale range. Alterations in the
      cytoplasmic organization, nuclear morphology, cell cycle progression, and
      expression of genes linked to cell cycle-dependent metabolic stress through EGR1,
      CCND, and E2F1 genes were the primary indicators of metabolic stress. Overall,
      the results of this study demonstrate that synthetic SiO2 acutely affects hMSC
      through cell cycle-dependent oxidative stress gene network. The toxicity
      mechanisms (both acute and chronic) of food grade silica should be investigated
      in greater depth with special reference to food safety.

PMID- 25374142
TI  - Autohydrolysis pretreatment of waste wheat straw for cellulosic ethanol
      production in a co-located straw pulp mill.
AB  - Waste wheat straw (WWS) is the waste product from feedstock preparation process
      in a straw pulp mill. It has a significant annual production rate and no
      commercial value has been explored on this material. In this study, waste wheat
      straw was pretreated using an autohydrolysis process followed by mechanical
      refining, and the pretreated materials were further enzymatically hydrolyzed to
      evaluate the total sugar recovery for bioethanol production. Results show that
      autohydrolysis at 170  degrees C for 40 min followed by 6000 revolution PFI
      refining provided the best result in this study, where a total sugar recovery
      (total sugars in autohydrolysis filtrate and enzymatic hydrolyzate over total
      carbohydrates on raw WWS) of 70 % at 4 filter paper unit per oven dry gram
      (FPU/OD g) substrate enzyme charge could be obtained. The economic evaluation of
      this biorefinery process indicates that cellulosic ethanol production from
      autohydrolysis of WWS is a very profitable business, with 28.4 % of internal rate
      of return can be achieved based on current ethanol wholesale price in China.

PMID- 25374143
TI  - Yttrium-90 Radioembolization as Salvage Therapy for Liver Metastases From
      Colorectal Cancer.
AB  - PURPOSE: To report safety and survival outcomes of Yttrium-90 (Y-90)
      radioembolization when used as salvage therapy for chemotherapy-resistant liver
      metastases from colorectal cancer. METHODS: In this IRB-approved retrospective
      study, 45 patients with hepatic metastases from colorectal cancer underwent Y-90
      radioembolization after failure of systemic chemotherapy. Toxicities were
      assessed as per NCI-CTCAE and response based on RECIST and PET. Kaplan-Meier
      survival analysis was performed to calculate median survival, prognostic factors
      on univariate analysis, and Cox regression analysis for independent predictors of
      survival. RESULTS: Y-90 radioembolization was technically successful in all
      (100%). Twenty-three patients (51%) had no toxicities, whereas 6 patients (13%)
      had grade 3 toxicities, and no patients had grade 4 toxicity. Two patients died
      within 30 days of treatment from renal failure unrelated to the procedure. Per
      RECIST, 1 patient (2%) had partial response, 34 (71%) had stable disease, and 6
      (13%) had progressive disease. PET response was seen in 46% of patients with 2
      patients (4%) demonstrating complete and 22 (42%) demonstrating partial metabolic
      response. The median survival was 186 days (95% CI, 149-277 d). Response on PET
      was the only independent predictor of superior overall survival. Patients who had
      response on PET following Y-90 therapy had a median overall survival of 317 days
      (10.6 mo) (95% CI, 193-564 d), whereas patients with no response on PET had a
      median overall survival of 163 days (5.4 mo) (95% CI, 64-283 d). CONCLUSIONS: Y
      90 radioembolization as a salvage therapy for chemotherapy-resistant hepatic
      metastases from colon cancer was safe and resulted in disease stability. Response
      on PET was an independent predictor of superior overall survival.

PMID- 25374144
TI  - Differences in Funding Sources of Phase III Oncology Clinical Trials by Treatment
      Modality and Cancer Type.
AB  - OBJECTIVES: Given the limited resources available to conduct clinical trials, it
      is important to understand how trial sponsorship differs among different
      therapeutic modalities and cancer types and to consider the ramifications of
      these differences. METHODS: We searched clinicaltrials.gov for a cross-sectional
      register of active, phase III, randomized controlled trials (RCTs) studying
      treatment-related endpoints such as survival and recurrence for the 24 most
      prevalent malignancies. We classified the RCTs into 7 categories of therapeutic
      modality: (1) chemotherapy/other cancer-directed drugs, (2) targeted therapy, (3)
      surgery, (4) radiation therapy (RT), (5) RT with other modalities, (6)
      multimodality therapy without RT, and (7) other. RCTs were categorized as being
      funded by one or more of the following groups: (1) government, (2)
      hospital/university, (3) industry, and (4) other. chi analysis was performed to
      detect differences in funding source distribution between modalities and cancer
      types. RESULTS: The percentage of multimodality trials (5%) and radiation RCTs
      (4%) funded by industry was less than that for chemotherapy (32%, P<0.01) or
      targeted therapy (48%, P<0.01). Trials studying targeted therapy were less likely
      to have hospital/university funding than any of the other modalities (P<0.01 in
      each comparison). Trials of chemotherapy were more likely to be funded by
      industry if they also studied targeted therapy (P<0.01). CONCLUSION: RCTs
      studying targeted therapies are more likely to be funded by industry than trials
      studying multimodality therapy or radiation. The impact of industry funding
      versus institutional or governmental sources of funding for cancer research is
      unclear and requires further study.

PMID- 25374145
TI  - Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology
      Group CONTRE Study.
AB  - PURPOSE: Following preoperative chemoradiation and surgery, many patients with
      stage II to III rectal cancer are unable to tolerate full-dose adjuvant
      chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete
      Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed
      by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic
      response at surgery. METHODS: Patients with clinical stage II to III (T3 to T4
      and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by
      capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation
      therapy. Surgery was performed 6 to 10 weeks after chemoradiation. RESULTS:
      Thirty-nine patients were enrolled between August 2010 and June 2013. Median age
      was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%)
      stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom
      35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as
      planned. No unexpected toxicities were reported. All patients had resolution of
      bleeding and improvement of obstructive symptoms, with no complications requiring
      surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in
      13 patients (33%; 95% CI, 18.24%-47.76%). CONCLUSIONS: CONTRE seems to be a well
      tolerated alternative to the current standard treatment sequence. Evaluating its
      impact on long-term outcomes would require a large randomized trial, but using
      pathologic response as an endpoint, it could serve as a platform for assessing
      the addition of novel agents to preoperative treatment in stage II to III rectal
      cancer.

PMID- 25374146
TI  - Nitrogen acquisition in Agave tequilana from degradation of endophytic bacteria.
AB  - Plants form symbiotic associations with endophytic bacteria within tissues of
      leaves, stems, and roots. It is unclear whether or how plants obtain nitrogen
      from these endophytic bacteria. Here we present evidence showing nitrogen flow
      from endophytic bacteria to plants in a process that appears to involve oxidative
      degradation of bacteria. In our experiments we employed Agave tequilana and its
      seed-transmitted endophyte Bacillus tequilensis to elucidate organic nitrogen
      transfer from (15)N-labeled bacteria to plants. Bacillus tequilensis cells grown
      in a minimal medium with (15)NH4Cl as the nitrogen source were watered onto
      plants growing in sand. We traced incorporation of (15)N into tryptophan,
      deoxynucleosides and pheophytin derived from chlorophyll a. Probes for hydrogen
      peroxide show its presence during degradation of bacteria in plant tissues,
      supporting involvement of reactive oxygen in the degradation process. In another
      experiment to assess nitrogen absorbed as a result of endophytic colonization of
      plants we demonstrated that endophytic bacteria potentially transfer more
      nitrogen to plants and stimulate greater biomass in plants than heat-killed
      bacteria that do not colonize plants but instead degrade in the soil. Findings
      presented here support the hypothesis that some plants under nutrient limitation
      may degrade and obtain nitrogen from endophytic microbes. 

PMID- 25374147
TI  - Chronic recurrent multifocal osteomyelitis manifested as painful clavicular
      swelling: a case report.
AB  - BACKGROUND: Chronic recurrent multifocal osteomyelitis is a form of non-bacterial
      osteomyelitis which occurs primarily in childhood. In some cases painful bone
      swelling occurs. After a malignancy has been ruled out, antibiotic therapy is
      often started to treat the osteomyelitis. The course of this benign disease is
      self-limiting and is not positively affected by the antibiotic therapy. CASE
      PRESENTATION: A 14-year-old German girl from South Africa came to the surgery
      with painful swelling in the right clavicle. The condition had first appeared two
      months earlier. The patient was unable to identify a trigger. In addition, the
      patient exhibited painless swelling in the area of the 5th metatarsal of the left
      foot. Chronic recurrent multifocal osteomyelitis was diagnosed based on
      characteristic clinical symptoms and imaging. Treatment with ibuprofen had caused
      the symptoms to regress rapidly. CONCLUSION: The case demonstrates to general
      practitioners and other clinicians that a prolonged administration of antibiotics
      can be prevented by means of a comprehensive diagnostic procedure for possible
      bacterial osteomyelitis.

PMID- 25374148
TI  - Differential protein expression profiling of Arabidopsis thaliana callus under
      microgravity on board the Chinese SZ-8 spacecraft.
AB  - MAIN CONCLUSION: Exposure of Arabidopsis callus to microgravity has a significant
      impact on the expression of proteins involved in stress responses, carbohydrate
      metabolism, protein synthesis, intracellular trafficking, signaling, and cell
      wall biosynthesis. Microgravity is among the main environmental stress factors
      that affect plant growth and development in space. Understanding how plants
      acclimate to space microgravity is important to develop bioregenerative life
      support systems for long-term space missions. To evaluate the spaceflight
      associated stress and identify molecular events important for acquired
      microgravity tolerance, we compared proteomic profiles of Arabidopsis thaliana
      callus grown under microgravity on board the Chinese spacecraft SZ-8 with callus
      grown under 1g centrifugation (1g control) in space. Alterations in the proteome
      induced by microgravity were analyzed by high performance liquid chromatography
      electrospray ionization-tandem mass spectrometry with isobaric tags for relative
      and absolute quantitation labeling. Forty-five proteins showed significant (p <
      0.05) and reproducible quantitative differences in expression between the
      microgravity and 1g control conditions. Of these proteins, the expression level
      of 24 proteins was significantly up-regulated and that of 21 proteins was
      significantly down-regulated. The functions of these proteins were involved in a
      wide range of cellular processes, including general stress responses,
      carbohydrate metabolism, protein synthesis/degradation, intracellular
      trafficking/transportation, signaling, and cell wall biosynthesis. Several
      proteins not previously known to be involved in the response to microgravity or
      gravitational stimuli, such as pathogenesis-related thaumatin-like protein,
      leucine-rich repeat extension-like protein, and temperature-induce lipocalin,
      were significantly up- or down-regulated by microgravity. The results imply that
      either the normal gravity-response signaling is affected by microgravity exposure
      or that microgravity might inappropriately induce altered responses to other
      environmental stresses.

PMID- 25374150
TI  - Exciton-like electromagnetic excitations in non-ideal microcavity supercrystals.
AB  - We study localized photonic excitations in a quasi-two-dimensional non-ideal
      binary microcavity lattice with use of the virtual crystal approximation. The
      effect of point defects (vacancies) on the excitation spectrum is investigated by
      numerical modelling. We obtain the dispersion and the energy gap of the
      electromagnetic excitations which may be considered as Frenkel exciton-like
      quasiparticles and analyze the dependence of their density of states on the
      defect concentrations in a microcavity supercrystal. 

PMID- 25374149
TI  - Chordopoxvirus protein F12 implicated in enveloped virion morphogenesis is an
      inactivated DNA polymerase.
AB  - Through the course of their evolution, viruses with large genomes have acquired
      numerous host genes, most of which perform function in virus reproduction in a
      manner that is related to their original activities in the cells, but some are
      exapted for new roles. Here we report the unexpected finding that protein F12,
      which is conserved among the chordopoxviruses and is implicated in the
      morphogenesis of enveloped intracellular virions, is a derived DNA polymerase,
      possibly of bacteriophage origin, in which the polymerase domain and probably the
      exonuclease domain have been inactivated. Thus, F12 appears to present a rare
      example of a drastic, exaptive functional change in virus evolution. REVIEWERS:
      This article was reviewed by Frank Eisenhaber and Juergen Brosius.

PMID- 25374151
TI  - General design of hollow porous CoFe2O4 nanocubes from metal-organic frameworks
      with extraordinary lithium storage.
AB  - Hollow porous CoFe(2)O(4) nanocubes from metal-organic frameworks were fabricated
      through a general facile strategy. The intrinsic hollow nanostructure can shorten
      the lengths for both electronic and ionic transport, enlarge the surface area of
      electrodes, and improve accommodation of the volume change during Li
      insertion/extraction cycling. The hybrid multi-elements characteristics allow the
      volume change to take place in a stepwise manner during the electrochemical
      cycle. Therefore, the as-prepared CoFe(2)O(4) electrode exhibits outstanding
      performance as anode materials for lithium ion batteries. The stable capacity
      arrives at 815 mA h g(-1) for 20 C. Subsequently, a specific capacity of ca. 1043
      mA h g(-1) is recovered when the current rate reduces back to 1 C after 200
      cycles. This general strategy may shed light on a new avenue for large-scale
      synthesis of hollow porous hybrid nanocubes via MOFs for energy storage,
      environmental remediation and other novel applications.

PMID- 25374152
TI  - Prenatal testing for hemolytic disease of the newborn and fetal neonatal
      alloimmune thrombocytopenia - current status.
AB  - Incompatibility of red cell and platelet antigens can lead to maternal
      alloimmunization causing hemolytic disease of the fetus & newborn and fetal
      neonatal alloimmune thrombocytopenia respectively. As the molecular background of
      these polymorphisms emerged, prenatal testing using initially fetal DNA obtained
      from invasively obtained amniotic fluid or chorionic villus was implemented. This
      evolved into testing using maternal plasma as source of fetal DNA, and this is in
      routine use as a safe non-invasive diagnostic that has no risk to the fetus of
      alloimmunization or spontaneous miscarriage. These tests were initially applied
      to high risk pregnancies, but has been applied on a mass scale, to screen fetuses
      in D-negative pregnant populations as national screening programs. Fetal neonatal
      alloimmune thrombocytopenia management has had comparatively small take up in non
      invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass
      scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their
      treatment with prophylactic anti-HPA-1A is being considered in at least one
      country (Norway). 

PMID- 25374153
TI  - Interaction of erythrocyte eicosapentaenoic acid and physical activity predicts
      reduced risk of mild cognitive impairment.
AB  - OBJECTIVES: To evaluate relationships between self-reported physical activity,
      proportions of long-chain omega-3 polyunsaturated fatty acids (LCn3) in
      erythrocyte content (percentage of total fatty acids) and risk of mild cognitive
      impairment (MCI) in older adults. METHOD: A cross-sectional study was conducted.
      Community-dwelling male and female (n = 84) participants over the age of 65 years
      with and without MCI were tested for erythrocyte proportions of the LCn3s
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Physical activity was
      measured using a validated questionnaire. RESULTS: The interaction between
      erythrocyte EPA, but not DHA, and increased physical activity was associated with
      increased odds of a non-MCI classification. CONCLUSION: An interaction between
      physical activity and erythrocyte EPA content (percentage of fatty acids)
      significantly predicted MCI status in older adults. Randomised control trials are
      needed to examine the potential for supplementation with EPA in combination with
      increased physical activity to mitigate the risk of MCI in ageing adults.

PMID- 25374154
TI  - Bimanual Fine Motor Function (BFMF) Classification in Children with Cerebral
      Palsy: Aspects of Construct and Content Validity.
AB  - The Bimanual Fine Motor Function (BFMF) is currently the principal classification
      of hand function recorded by the Surveillance of Cerebral Palsy in Europe (SCPE)
      register. The BFMF is used in a number of epidemiological studies, but has not
      yet been validated. AIMS: To examine aspects of construct and content validity of
      the BFMF. METHODS AND RESULTS: Construct validity of the BFMF was assessed by
      comparison with the Manual Ability Classification System (MACS) using register
      based data from 539 children born 1999-2003 (304 boys; 4-12 years). The high
      correlation with the MACS (Spearman's rho = 0.89, CI: 0.86-0.91, p<.001) supports
      construct validity of the BFMF. The content of the BFMF was appraised through
      literature review, and by using the ICF-CY as a framework to compare the BFMF and
      MACS. The items hold, grasp and manipulate were found to be relevant to describe
      increasingly advanced fine motor abilities in children with CP, but the
      description of the BFMF does not state whether it is a classification of fine
      motor capacity or performance. CONCLUSION: Our results suggest that the BFMF may
      provide complementary information to the MACS regarding fine motor function and
      actual use of the hands, particularly if used as a classification of fine motor
      capacity.

PMID- 25374155
TI  - Using Posturography to Examine the Immediate Effects of Vestibular Therapy for
      Children with Autism Spectrum Disorders: A Feasibility Study.
AB  - AIMS: The primary objective of this study was to determine the feasibility of
      using posturography to monitor acute changes in postural control induced by a
      Sensory Integration (SI) therapy intervention. A secondary objective was to
      identify which posturography outcome parameters, tests conditions and data
      analysis methods might be most useful in identifying post-intervention changes.
      METHODS: Five children with Autism Spectrum Disorder (ASD) and five children with
      typical development (TD) participated in a 10 min vestibular swing activity and
      had their postural stability evaluated pre- and post-intervention under four
      different sensory testing conditions. Sway ranges, mean sway velocity, sway root
      mean square (RMS), and sample entropy were calculated from center of pressure
      (COP) data. RESULTS: All five children with ASD demonstrated decreased mean sway
      velocity in the eyes open/flat plate condition post-intervention with an average
      decrease of 5.87 +/- 2.69 mm/s. Four of the five children with ASD demonstrated
      an increase in RMS and a decrease in anterior/posterior sample entropy post
      intervention in the eyes closed, foam pad condition and eyes open, flat plate
      condition respectively. CONCLUSION: Posturography may be useful for assessing
      acute physiologic responses to an SI therapy intervention and warrants further
      investigation.

PMID- 25374156
TI  - Inter-Rater and Test-Retest Reliability of the German Pediatric Evaluation of
      Disability Inventory (PEDI-G).
AB  - ABSTRACT Activities of daily living (ADL) of children are widely assessed with
      the Pediatric Evaluation Disability Inventory (PEDI). This study examined test
      retest and inter-rater reliability of the German PEDI (PEDI-G). During the
      adaptation of the PEDI nine items were added. In total, 117 parents of 53
      children without and 64 children with a diagnosed physical disability from
      Austria, Germany, and Switzerland participated. Reliability was examined by
      intraclass correlation coefficient (ICC), standard error of measurement (SEM) and
      smallest detectable difference (SDD) for the Functional Skill Scale with and
      without added items and the Caregiver Assistance Scale. Cohen's Kappa was used to
      calculate the reliability of the Modification Scale. All ICC's for test-retest
      and inter-rater reliability were above 0.75, indicating good to very good
      reliability. The SDD varied from 0.83-5.58 across PEDI domains and scales. For
      the Modification Scale, Cohen's weighted kappa varied from 0.25 to 1.00
      indicating sufficient reliability for some but not all items. Our findings
      indicate that the Functional Skill Scale and the Caregiver Assistance Scale of
      the PEDI-G are reliable scales that can be used to evaluate ADLs of children with
      and without physical disability.

PMID- 25374157
TI  - Microglial activation occurs in the absence of anxiety-like behavior following
      microembolic stroke in female, but not male, rats.
AB  - BACKGROUND: The incidence of depression and anxiety disorders is twice as high in
      women than men; however, females exhibit less neuronal damage following an
      equivalent ischemic event. Microembolic stroke increases anxiety- and depressive
      like behaviors in male rats but the behavioral repercussions in females are
      unknown. FINDINGS: Given the relative neuronal protection from stroke in ovary
      intact females, female rats exposed to microembolic stroke may be behaviorally
      protected as compared to males. The data presented demonstrate that anxiety-like
      behavior is increased in males despite a comparable increase in microglial
      activation following microembolic stroke in both males and females. CONCLUSIONS:
      These data suggest that males may be more behaviorally susceptible to the effects
      of microembolic stroke and further illustrate a dissociation between
      neuroinflammation and behavior in females.

PMID- 25374158
TI  - Differentiation of human amniotic epithelial cells into Schwann-like cells via
      indirect co-culture with Schwann cells in vitro.
AB  - Human amniotic epithelial cells (hAECs) exhibit multi-lineage differentiation
      ability. The present study investigated the possibility that hAECs possess the
      potential to differentiate into Schwann-like cells using an in vitro indirect co
      culture approach. hAECs were isolated via enzymatic digestion, and
      immunocytochemistry and flow cytometry were performed to identify the hAECs. The
      hAECs were co-cultured with Schwann cells (SCs) to differentiate the hAECs into
      Schwann-like cells via induced proximity. The expression of typical S-100 SC
      markers in the co-cultured hAECs was determined via immunocytochemistry. For the
      functional experiments, reverse transcription quantitative polymerase chain
      reaction (RT-qPCR) was performed to measure the expression levels of nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell-derived
      neurotrophic factor (GDNF) mRNA. In addition, neurite outgrowth was measured in
      PC12 cells following co-culture with the differentiated hAECs. Subsequent to co
      culture with SCs for 21 days, the hAECs exhibited spindle-like morphology. The
      immunocytochemistry results revealed that the co-cultured hAECs expressed S-100,
      indicating differentiation into Schwann-like cells. RT-qPCR revealed that NGF,
      BDNF and GDNF expression was upregulated upon differentiation. The average axon
      length of the PC12 cells increased from 21.32+/-5.45 to 51.32+/-8.56 um
      subsequent to co-culture with the differentiated hAECs. These results demonstrate
      that this indirect co-culture microenvironment induced the hAECs to differentiate
      into Schwann-like cells that exhibited the morphological, phenotypic and
      functional characteristics of SCs. Therefore, the use of differentiated hAECs
      that exhibit the characteristics of SCs provides a promising alternative to the
      present techniques used for peripheral nerve regeneration. 

PMID- 25374159
TI  - Chemical and mass spectrometry characterization of the red alga Pyropia yezoensis
      chemoprotective protein (PYP): protective activity of the N-terminal fragment of
      PYP1 against acetaminophen-induced cell death in Chang liver cells.
AB  - In the present study, the chemical structure and chemoprotective activity of
      Pyropia yezoensis protein (PYP) were investigated using sodium dodecyl sulfate
      (SDS)-polyacrylamide gel electrophoresis, automated protein sequencing, matrix
      assisted laser desorption/ionization-quadrupole ion trap-time-of-flight mass
      spectrometry and a chemoprotective assay using a synthetic peptide. The PYP
      fraction was demonstrated to contain two proteins: PYP1 (10 kDa, SDS-resistant
      dimer) and PYP2 (10 kDa). PYP1 is a novel protein showing sequence homology with
      the hypothetical function-unknown proteins of Chondrus crispus (Rhodophyta) and
      Emiliania huxleyi (Haptophyceae). PYP2 is a paralog of an extrinsic protein of
      photosystem II found in other Rhodophyta. The synthetic peptide PYP1 (1-20),
      corresponding to the N-terminal 20 residues of PYP1 (ALEGGKSSGGGEATRDPEPT),
      exhibits chemoprotective activity against acetaminophen-induced cell death in
      Chang liver cells, indicating that PYP1 is a chemoprotectant of the PYP fraction.
      A possible association between the structure of PYP and its chemoprotective
      activity is discussed.

PMID- 25374161
TI  - The method of isolation of the crayfish abdominal stretch receptor maintaining a
      connection of the sensory neuron to the ventral nerve cord ganglion.
AB  - The crayfish stretch receptor consisting of the single mechanoreceptor neurons
      enveloped by satellite glial cells is the simplest functioning neuroglial
      preparation. However, during isolation, its axons are usually transected that
      eliminates afferent regulation and induces complex axotomy-related signaling
      responses in neurons and satellite glia. We developed new microsurgical method of
      crayfish stretch receptor isolation, which preserves connections of sensory
      neurons to the ventral nerve cord ganglion. The stretch receptor may either
      remain on the abdominal carapace, or be completely isolated. In both cases, it
      may be either intact, or axotomized. The integrity of axons was confirmed by
      firing recording from proximal and distal axon points. Normal, necrotic and
      apoptotic cells were visualized using double fluorochroming with Hoechst 33342
      and propidium iodide. The isolated mechanoreceptor neurons maintain regular
      firing during 8-10 or more hours. Glial cells surrounding non-axotomized neurons
      demonstrate lower necrosis and apoptosis levels than the axotomized ones. Unlike
      the existing method, in which the sensory neurons were axotomized, the present
      method preserves links between the sensory neurons and the ganglion and makes
      possible to avoid consequences of axotomy in neurons and satellite glia. The
      present neuroglial preparation may be used as a simple but informative model
      object in studies of axotomy-induced degeneration and survival of peripheral
      neurons, the role of glia in neuron injury, the signaling mechanisms of
      neuroglial interactions, and the effects of diverse physical and chemical factors
      on neuronal and glial cells. 

PMID- 25374160
TI  - Distribution of metals exposure and associations with cardiometabolic risk
      factors in the "Modeling the Epidemiologic Transition Study".
AB  - BACKGROUND: Metals are known endocrine disruptors and have been linked to
      cardiometabolic diseases via multiple potential mechanisms, yet few human studies
      have both the exposure variability and biologically-relevant phenotype data
      available. We sought to examine the distribution of metals exposure and potential
      associations with cardiometabolic risk factors in the "Modeling the Epidemiologic
      Transition Study" (METS), a prospective cohort study designed to assess energy
      balance and change in body weight, diabetes and cardiovascular disease risk in
      five countries at different stages of social and economic development. METHODS:
      Young adults (25-45 years) of African descent were enrolled (N = 500 from each
      site) in: Ghana, South Africa, Seychelles, Jamaica and the U.S.A. We randomly
      selected 150 blood samples (N = 30 from each site) to determine concentrations of
      selected metals (arsenic, cadmium, lead, mercury) in a subset of participants at
      baseline and to examine associations with cardiometabolic risk factors. RESULTS:
      Median (interquartile range) metal concentrations (MUg/L) were: arsenic 8.5
      (7.7); cadmium 0.01 (0.8); lead 16.6 (16.1); and mercury 1.5 (5.0). There were
      significant differences in metals concentrations by: site location, paid
      employment status, education, marital status, smoking, alcohol use, and fish
      intake. After adjusting for these covariates plus age and sex, arsenic (OR 4.1,
      95% C.I. 1.2, 14.6) and lead (OR 4.0, 95% C.I. 1.6, 9.6) above the median values
      were significantly associated with elevated fasting glucose. These associations
      increased when models were further adjusted for percent body fat: arsenic (OR
      5.6, 95% C.I. 1.5, 21.2) and lead (OR 5.0, 95% C.I. 2.0, 12.7). Cadmium and
      mercury were also related with increased odds of elevated fasting glucose, but
      the associations were not statistically significant. Arsenic was significantly
      associated with increased odds of low HDL cholesterol both with (OR 8.0, 95% C.I.
      1.8, 35.0) and without (OR 5.9, 95% C.I. 1.5, 23.1) adjustment for percent body
      fat. CONCLUSIONS: While not consistent for all cardiometabolic disease markers,
      these results are suggestive of potentially important associations between metals
      exposure and cardiometabolic risk. Future studies will examine these associations
      in the larger cohort over time.

PMID- 25374162
TI  - Biosensing by luminogens with aggregation-induced emission characteristics.
AB  - Fluorescent biosensors are powerful analytical tools for studying biological
      events in living systems. Luminescent materials with aggregation-induced emission
      (AIE) attributes have attracted much research interest and have been identified
      as a novel class of luminogens to develop fluorescent turn-on biosensors with
      superior sensitivity. In this Tutorial Review, we present an overview of the AIE
      phenomenon and its mechanism. We summarize the structural design and working
      principle of AIE biosensors developed recently. Typical examples of AIE
      biosensors are presented. 

PMID- 25374163
TI  - Protein-protein interaction modulator drug discovery: past efforts and future
      opportunities using a rich source of low- and high-throughput screening assays.
AB  - INTRODUCTION: Historically, small-molecule drug discovery projects have largely
      focused on the G-protein-coupled receptor, ion-channel and enzyme target classes.
      More recently, there have been successes demonstrating that protein-protein
      interactions (PPIs) can be targeted by small-molecules and that this strategy has
      the potential to provide appropriate specificity and selectivity. However, a
      disadvantage is that compounds that modulate PPIs are often associated with
      relatively weak affinities as the targeted interaction surfaces are often
      relatively large. Moreover, from a small-molecule screening perspective, a large
      proportion of the initial screening Hits are often false positives and these need
      to be identified and excluded in order to focus on genuine modulators of the PPI
      being investigated. AREAS COVERED: The authors review previous efforts on PPI
      modulator drug discovery. Furthermore, they review assays that can be employed in
      small-molecule screening and/or Hit validation. The PPI assays are categorized
      as: i) low-throughput target-based biochemical assays, which are primarily
      employed for Hit validation at the post-screening stage; ii) high-throughput
      target-based biochemical assays that are suitable for screening campaigns; and
      iii) cell-based assays, which are suitable for high-throughput screening
      campaigns and/or Hit validation. EXPERT OPINION: Modulating the interaction of
      PPIs offers the potential to develop novel drugs to treat a wide range of
      diseases. New assay technologies are continually being developed and it is
      anticipated that these will be able to be directly used for small-molecule
      screening campaigns in the future.

PMID- 25374164
TI  - Research progress in applying proteomics technology to explore early diagnosis
      biomarkers of breast cancer, lung cancer and ovarian cancer.
AB  - According to the China tumor registry 2013 annual report , breast cancer, lung
      cancer, and ovarian cancer are three common cancers in China nowadays, with high
      mortality due to the absence of early diagnosis technology. However, proteomics
      has been widespreadly implanted into every field of life science and medicine as
      an important part of post-genomics era research. The development of theory and
      technology in proteomics has provided new ideas and research fields for cancer
      research. Proteomics can be used not only for elucidating the mechanisms of
      carcinogenesis focussing on whole proteins of the tissue or cell, but also
      seeking the biomarkers for diagnosis and therapy of cancer. In this review, we
      introduce proteomics principles, covering current technology used in exploring
      early diagnosis biomarkers of breast cancer, lung cancer and ovarian cancer. 

PMID- 25374165
TI  - Mitogen-activated protein kinase signal transduction in solid tumors.
AB  - Mitogen-activated protein kinase (MAPK) is an important signaling pathway in
      living beings in response to extracellular stimuli. There are 5 main subgroups
      manipulating by a set of sequential actions: ERK(ERK1/ ERK2), c-Jun N(JNK/SAPK),
      p38 MAPK(p38alpha, p38beta, p38gamma and p38delta), and ERK3/ ERK4/ ERK5. When
      stimulated, factors of upstream or downstream change, and by interacting with
      each other, these groups have long been recognized to be related to multiple
      biologic processes such as cell proliferation, differentiation, death, migration,
      invasion and inflammation. However, once abnormally activated, cancer may occur.
      Several components of the MAPK network have already been proposed as targets in
      cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them,
      alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been
      reported in human cancer as a result of abnormal activation of receptor tyrosine
      kinases or gain-of-function mutations in genes. The reported roles of MAPK
      signaling in apoptotic cell death are controversial, so that further in-depth
      investigations are needed to address these controversies. Based on an extensive
      analysis of published data, the goal of this review is to provide an overview on
      recent studies about the mechanism of MAP kinases, and how it generates certain
      tumors, as well as related treatments. 

PMID- 25374166
TI  - Cancer stem cells and stemness markers in oral squamous cell carcinomas.
AB  - Head and neck squamous cell carcinoma (HNSCC) is one of the world top ten most
      common cancers with its highest occurrence in the Indian subcontinent and
      different aggressive and etiological behavioural patterns. The scenario is only
      getting worst with the 5 year survival rates dropping to 50%, persistent
      treatment failures and frequent cases of relapse/recurrence. One of the major
      reasons for these failures is the presence of cancer stem cells (CSCs), a small
      population of cancer cells that are highly tumourigenic, capable of self-renewal
      and have the ability to differentiate into cells that constitute the bulk of
      tumours. Notably, recent evidence suggests that cancer stem cells are especially
      resistant to conventional therapy and are the "drivers" of local recurrence and
      metastatic spread. Specific markers for this population have been investigated in
      HNSCC in the hope of developing a deeper understanding of their role in oral
      cancer pathogenesis, elucidating novel biomarkers for early diagnosis and newer
      therapeutic strategies. This review covers the fundamental relevance of almost
      all the CSC biomarkers established to date with a special emphasis on their
      impact in the process of oral tumourigenesis and their potential role in
      improving the diagnosis, prognosis and treatment of OSCC patients. 

PMID- 25374167
TI  - Cancer pain prevalence and its management.
AB  - Pain is a public health problem affecting more than half of cancer patients.
      Despite the success of the protocols currently used, pain cannot still be reduced
      satisfactorily in the large majority of patients. In order to improve pain
      management, all healthcare professionals involved with pain should have
      sufficient knowledge on pain assessment and treatment, and should inform patients
      to prevent patient-related barriers. In this compilation, the prevalence values
      and the treatment methods of cancer pain, and the barriers to pain management
      have been assessed. 

PMID- 25374168
TI  - Self-collection tools for routine cervical cancer screening: a review.
AB  - Sub-optimal participation is a major problem with cervical cancer screening in
      developing countries which have no organized national screening program. There
      are various notable factors such as 'embarrassment', 'discomfort' and 'no time'
      cited by women as they are often also the bread winners for the family.
      Implementation of self-sampling methods may increase their participation. The aim
      of this article was to provide a survey of various types of self-sampling tools
      which are commonly used in collection of cervical cells. We reviewed currently
      available self-sampling devices and collated the advantages and disadvantages of
      each in terms of its acceptance and its accuracy in giving desired results. In
      general, regardless of which device is used, self-sampling for cervical scrapings
      is highly acceptable to women in most of the studies cited. 

PMID- 25374169
TI  - Health benefits of Moringa oleifera.
AB  - Phytomedicines are believed to have benefits over conventional drugs and are
      regaining interest in current research. Moringa oleifera is a multi-purpose
      herbal plant used as human food and an alternative for medicinal purposes
      worldwide. It has been identified by researchers as a plant with numerous health
      benefits including nutritional and medicinal advantages. Moringa oleifera
      contains essential amino acids, carotenoids in leaves, and components with
      nutraceutical properties, supporting the idea of using this plant as a
      nutritional supplement or constituent in food preparation. Some nutritional
      evaluation has been carried out in leaves and stem. An important factor that
      accounts for the medicinal uses of Moringa oleifera is its very wide range of
      vital antioxidants, antibiotics and nutrients including vitamins and minerals.
      Almost all parts from Moringa can be used as a source for nutrition with other
      useful values. This mini-review elaborate on details its health benefits. 

PMID- 25374170
TI  - Research progress on the livin gene and osteosarcomas.
AB  - Osteosarcoma is a common malignant tumor of bone, but mechanisms underlying its
      development are still unclear. At present, it is believed that the inhibition of
      normal apoptotic mechanisms is one of the reasons for the development of tumors,
      so specific stimulation of tumor cell apoptosis can be considered as an important
      therapeutic method. Livin, as a member of the newly discovered inhibitor of
      apoptosis proteins (IAPs) family, has specifically high expression in tumor
      tissues and can inhibit tumor cell apoptosis through multiple ways, which can
      become a new target for malignant tumor treatment (including osteosarcoma) and
      might of great significance in the clinical diagnosis of tumors and the screening
      of anti-tumor agents and carcinoma treatment. 

PMID- 25374171
TI  - hARIP2 is a putative growth-promoting factor involved in human colon
      tumorigenesis.
AB  - Activin is a multifunctional growth and differentiation factor of the growth
      factor-beta (TGF-beta) superfamily, which inhibits the proliferation of colon
      cancer cells. It induces phosphorylation of intracellular signaling molecules
      (Smads) by interacting with its type I and type II receptors. Previous studies
      showed that human activin receptor-interacting protein 2 (hARIP2) can reduce
      activin signaling by interacting with activin type II receptors; however, the
      activity of hARIP2 in colon cancer has yet to be detailed. In vitro,
      overexpression of hARIP2 reduced activin-induced transcriptional activity and
      enhanced cell proliferation and colony formation in human colon cancer HCT8 cells
      and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis, suggesting
      that a vital role in the initial stage of colon carcinogenesis. In vivo,
      immunohistochemistry revealed that hARIP2 was expressed more frequently and much
      more intensely in malignant colon tissues than in controls. These results
      indicate that hARIP2 is involved in human colon tumorigenesis and could be a
      predictive maker for colon carcinoma aggressiveness. 

PMID- 25374172
TI  - Prevalence of local recurrence of colorectal cancer at the Iranian Cancer
      Institute.
AB  - BACKGROUND: Although a great deal of progress has been made in the management of
      colorectal cancer in terms of neoadjuvant modalities, surgical techniques and
      adjuvant therapies, the recurrence of tumors remains an enigmatic complication in
      patients. A better understanding of colorectal cancer and of factors that lead to
      recurrence of disease can provide helpful information for designing more
      effective screening and surveillance methods. AIM: To investigate the factors
      that may lead to local recurrence of colorectal cancers. MATERIALS AND METHODS:
      The current retrospective case study evaluated 617 patients admitted to the
      Iranian Cancer Institute (the largest referral cancer center in the country) from
      1995 to 2009 with confirmed colorectal cancer. Patients with distant metastasis,
      or with pathology other than adenocarcinoma and no follow-up, were excluded (175
      patients). The remainder (442) included 294 (66.5%) with rectal cancer and 148
      (33.5%) with colon cancer. The median duration of follow-up was 26 months.
      RESULTS: The total rate of recurrence was 17.4%, comprising 19.6% and 16.3%
      recurrence rates in colon and rectal cancer, respectively. CONCLUSIONS:
      Recurrence of colorectal cancer was significantly correlated to tumor grade
      (p<0.008).

PMID- 25374173
TI  - Outcome of daily cisplatin with thoracic chemoradiotherapy in advanced non-small
      cell lung cancer patients with comorbid disorders: a pilot study.
AB  - BACKGROUND: Lung cancer is the most common cancer in males worldwide. The
      principal mode of treatment in the early stage of non-small cell lung cancer
      (NSCLC) is surgery. However, five-year survival is only about 15% for all stages.
      The aim is to investigate the effect of daily low dose cisplatin concurrently
      with radiation therapy in advanced NSCLC patients with poor performance status.
      MATERIALS AND METHODS: Ten patients diagnosed as inoperable Stage IIIB NSCLC with
      comorbid disease were assessed retrospectively in Bezmialem Vakif University,
      Faculty of Medicine, Department of Radiation Oncology, between 2011 to 2013. ECOG
      performance status was between 3 and 4. Cisplatin was administered at 6 mg/m2
      daily, for 5 days a week concurrently with radiotherapy using 160-200 cGy daily
      fractions, 54 Gy being the lowest and 63 Gy being the highest dose. RESULTS:
      Complete response at the primary tumour site was obtained in 20% patients. Grade
      I esophagitis was seen 70 percent of patients, and the grade II haematological
      toxicity rate was 20%. Median survival time was 7 months. CONCLUSIONS: Median
      survival time was reasonable, despite the patients ECOG performance status of 3
      4, which is similar to groups even without comorbid disorders in comparison to
      other published papers in the literature. Acceptable toxicity, high response
      rates and quality of life of patients are the other favourable features.

PMID- 25374174
TI  - miR-200a overexpression in advanced ovarian carcinomas as a prognostic indicator.
AB  - BACKGROUND: miR-200a expression is frequently altered in numerous cancers. The
      aim of the present study was to determine the role of microRNA-200a in advanced
      ovarian carcinomas. MATERIALS AND METHODS: We measured miR-200a expression in 72
      matched normal ovarian tissues and advanced ovarian carcinomas, and also two
      ovarian carcinoma cell lines (SKOV3 and SKOV3.ip1--the latter being more invasive
      and metastatic than the parental SKOV3) by stem-loop real-time RT-PCR based on
      TaqMan microRNA assay using U6 as a reference. Levels of miR-200a expression were
      compared by disease stage, tumor grade, histology, and lymph node involvement. To
      evaluate the role of microRNA-200a, cell proliferation and invasion of SKOV-3 and
      SKOV-3.ip1 were analyzed with miR-200a inhibitor/mimic transfected cells.
      RESULTS: Of 72 paired samples, 65 cancer tissues overexpressed microRNA-200a
      greater than two fold in comparison with matched normal epithelium. Specifically,
      patients with lymph node metastasis showed significant elevation. The level
      correlated with clinicopathological features, including high tumor grade, late
      disease stage, most notably with lymph node metastasis, but not with tumor
      histology. In addition, SKOV-3.ip1 cells also overexpressed miR-200a compared
      with SKOV-3, and miR-200a inhibitor transfected SKOV-3.ip1 cells showed
      significant reduction in cellular proliferation and invasion, while a miR-200a
      mimic stimulated the opposite behavior. CONCLUSIONS: We provide definitive
      evidence that miR-200a is up-regulated in a significant proportion of advanced
      ovarian carcinomas, and that elevated miR-200a expression facilitates tumor
      progression. Our findings support the notion that miR- 200a is an onco-microRNA
      for ovarian cancer, and elevation is a useful potential diagnostic indicator.
      This study also provides a solid basis for further functional analysis of miR
      200a in advanced ovarian cancer.

PMID- 25374175
TI  - Safety of Brucea javanica and cantharidin combined with chemotherapy for
      treatment of NSCLC patients.
AB  - OBJECTIVE: To assess the safety of Brucea javanica and Cantharidin combined with
      chemotherapy in treating patients with non-small-cell lung carcinoma. METHOD: A
      consecutive cohort of patients with NSCLC were divided into four groups:
      experimental group A treated with Brucea javanica injection combined with
      chemotherapy; experimental group B with Cantharidin injection combined with
      chemotherapy; experimental group C treated with Brucea javanica and Cantharidin
      injection combined with chemotherapy; and the control group receiving only
      chemotherapy. After more than two courses of treatment, safety, quality of life
      and side effects were evaluated. RESULTS: The incidences of myelosuppression in
      groups A, B and C were lower than that in Control group (p<0.05), but without
      significant differences among A, B and C. Adverse effects on the gastrointestinal
      tract also were lower than in controls (p<0.05) without variation amnog the
      combined treatment groups. CONCLUSIONS: Brucea javanica or Cantharidin combined
      with chemotherapy could in both cases improve quality of life in our cohort of
      NSCLC patients without any increase in toxicity. However, further clinical
      experiments should be conducted to evaluate the efficacy of Brucea javanica and
      Cantharidin combined with chemotherapy for patients with NSCLC.

PMID- 25374176
TI  - Association between socioeconomic status and altered appearance distress, body
      image, and quality of life among breast cancer patients.
AB  - BACKGROUND: Breast cancer patients experience a variety of altered appearance-
      such as loss or disfigurement of breasts, discolored skin, and hair loss--which
      result in psychological distress that affect their quality of life. This study
      aims to evaluate the impact of socioeconomic status on the altered appearance
      distress, body image, and quality of life among Korean breast cancer patients.
      MATERIALS AND METHODS: A cross-sectional survey was conducted at advocacy events
      held at 16 different hospitals in Korea. Subjects were eligible to participate if
      they were 18 years of age or older, had a histologically confirmed diagnosis of
      breast cancer, had no evidence of recurrence or metastasis, and had no
      psychological problems at the time of the survey. Employment status, marital
      status, education, and income were assessed for patient socioeconomic status.
      Altered appearance distress was measured using the NCI's cancer treatment side
      effects scale; body image and quality of life were measured by the EORTC QLC-C30
      and BR23. Means and standard deviations of each outcome were compared by
      socioeconomic status and multivariate linear regression models for evaluating the
      association between socioeconomic status and altered appearance distress, body
      image, and quality of life. RESULTS: A total of 126 breast cancer patients
      participated in the study; the mean age of participants was 47.7 (SD=8.4). Of the
      total, 83.2% were married, 85.6% received more than high school education, 35.2%
      were employed, and 41% had more than $3000 in monthly household income. About 46%
      had mastectomy, and over 30% were receiving either chemotherapy or radiation
      therapy at the time of the survey. With fully adjusted models, the employed
      patients had significantly higher altered appearance distress (1.80 vs 1.48;
      p<0.05) and poorer body image (36.63 vs 51.69; p<0.05) compared to the patients
      who were unemployed. Higher education (10.58, standard error (SE)=7.63) and
      family income (12.88, SE=5.08) was positively associated with better body image
      after adjusting for age, disease stage at diagnosis, current treatment status,
      and breast surgery type. Similarly, patients who were married and who had higher
      education had better quality of life were statistically significant in the
      multivariate models. CONCLUSIONS: Socioeconomic status is significantly
      associated with altered appearance distress, body image, and quality of life in
      Korean women with breast cancer. Patients who suffer from altered appearance
      distress or lower body image are much more likely to experience psychosocial,
      physical, and functional problems than women who do not, therefore health care
      providers should be aware of the changes and distresses that these breast cancer
      patients go through and provide specific information and psychosocial support to
      socioeconomically more vulnerable patients.

PMID- 25374177
TI  - Diagnostic value of ultrasound-guided fine needle aspiration biopsy in malignant
      thyroid nodules: utility for micronodules.
AB  - BACKGROUND: The diagnostic approach to thyroid nodules involves ultrasound-guided
      fine needle aspiration biopsy (US-FNAB).We especially aimed to evaluate the
      contribution and the place of US-FNAB in preoperative evaluation of the malignant
      cases and draw attention to discordant cases diagnosed with papillary thyroid
      microcarcinoma (PTMC). MATERIALS AND METHODS: A total of 276 cases were
      retrospectively reviewed who were subsequently diagnosed with a malignancy and
      who underwent US-FNAB. RESULTS: Some 45 were found to have previously undergone
      the US-FNAB procedure. Of the patients in whom the surgical specimen was
      diagnosed with a malignancy, 21 (46.7%) were diagnosed as malignant or suspicious
      for malignancy, and 24 (53.3%) were concluded as benign or insufficient for
      diagnosis. Patients with the diagnosis of PTMC outnumbering the others was a
      striking finding (11 cases, 24%). CONCLUSIONS: We suggest performing repeat
      aspiration biopsy considering sampling errors in cases where inconsistency exists
      between clinical findings and cytological results in thyroid nodules smaller than
      10 mm in diameter and with suspicious findings on ultrasonography.

PMID- 25374178
TI  - Roles of the Bcl-2/Bax ratio, caspase-8 and 9 in resistance of breast cancer
      cells to paclitaxel.
AB  - The goal of this study was to establish paclitaxel resistant MCF-7 cells, as in
      vitro model, to identify the molecular mechanisms leading to acquired
      chemoresistance in breast cancer cells. Resistant cells were developed by
      stepwise increasing exposure to paclitaxel. Gene expression levels of Bax and Bcl
      2 along with protein levels of caspase-8 and caspase-9 were evaluated in two
      resistant cell lines (MCF -7/Pac64 and MCF -7/Pac5 nM). Morphological
      modifications in paclitaxel resistance cells were examined by light microscopy
      and fluorescence activated cell sorting (FACS). As an important indicator of
      resistance to chemotheraputic agents, the Bcl-2/Bax ratio showed a significant
      increase in both MCF-7/Pac5nM and MCF-7/Pac 64nM cells (p<0.001), while caspase-9
      levels were decreased (p<0.001) and caspase-8 was increased (p<0.001). FACS
      analysis demonstrated that MCF -7/Pac64 cells were smaller than MCF-7 cells with
      no difference in their granularity. Our results support the idea that paclitaxel
      induces apoptosis in a mitochondrial-dependent manner. Identifying breast cancer
      patients with a higher Bcl-2/Bax ratio and caspase 9 level and then inhibiting
      the activity of these proteins may improve the efficacy of chemotheraputic
      agents. 

PMID- 25374179
TI  - Silencing of NUF2 inhibits tumor growth and induces apoptosis in human
      hepatocellular carcinomas.
AB  - BACKGROUND: As an important component of the NDC80 kinetochore complex, NUF2 is
      essential for kinetochore-microtubule attachment and chromosome segregation.
      Previous studies also suggested its involvement in development of various kinds
      of human cancers, however, its expression and functions in human hepatocellular
      carcinoma (HCC) are still unclear. MATERIALS AND METHODS: In the present study,
      we aimed to test the hypothesis that NUF2 is aberrant in human HCCs and
      associated with cell growth. RESULTS: Our results showed significantly elevated
      expression of NUF2 in human HCC tissues compared to adjacent normal tissues, and
      high expression of NUF2 in HCC cell lines. Using lentivirus-mediated silencing of
      NUF2 in HepG2 human HCC cells, we found that NUF2 depletion markedly suppressed
      proliferation and colony formation capacity in vitro, and dramatically hampered
      tumor growth of xenografts in vivo. Moreover, NUF2 silencing could induce cell
      cycle arrest and trigger cell apoptosis. Additionally, altered levels of cell
      cycle and apoptosis related proteins including cyclin B1, Cdc25A, Cdc2, Bad and
      Bax were also observed. CONCLUSIONS: In conclusion, these results demonstrate
      that NUF2 plays a critical role in the regulation of HCC cell proliferation and
      apoptosis, indicating that NUF2 may serve as a potential molecular target for
      therapeutic approaches.

PMID- 25374180
TI  - Expression and function of GSTA1 in lung cancer cells.
AB  - Glutathione S-transferase A1 (GSTA1) appears to be primarily involved in
      detoxification processes, but possible roles in lung cancer remain unclear. The
      objective of this study was to investigate the expression and function of GSTA1
      in lung cancer cells. Real-time PCR and Western blotting were performed to assess
      expression in cancer cell lines and the normal lung cells, then verify the A549
      cells line with stable overexpression. Localization of GSTA1 proteins was
      assessed by cytoimmunofluorescence. Three double-strand DNA oligoRNAs (SiRNAs)
      were synthesized prior to being transfected into A549 cells with Lipofectamine
      2000, and then the most efficient SiRNA was selected. Expression of the GSTA1
      gene in the transfected cells was determined by real-time PCR and Western
      blotting. The viability of the transfected cells were assessed by MTT. Results
      showed that the mRNA and protein expression of A549 cancer cells was higher than
      in MRC-5 normal cells. Cytoimmunofluorescence demonstrated GSTA1 localization in
      the cell cytoplasm and/or membranes. Transfection into A549 cells demonstrated
      that down-regulated expression could inhibit cell viability. Our data indicated
      that GSTA1 expression may be a target molecule in early diagnosis and treatment
      of lung cancer. 

PMID- 25374181
TI  - Knowledge, attitude and practice of breast self-examination among female
      university students from 24 low, middle income and emerging economy countries.
AB  - The aim of this study was to investigate the knowledge, attitude and practice of
      Breast Self-Examination (BSE) among female university students from 24 low,
      middle income and emerging economy countries. Using anonymous questionnaires,
      data were collected from 10,810 female undergraduate university students aged 16-
      30 (mean age 20.7, SD=2.9) from 25 universities in 24 countries across Asia,
      Africa and the Americas. Overall, 50.4% of the female students indicated that
      they knew how to conduct BSE. Among all women, 59.3% had never practiced BSE in
      the past 12 months, 21.3% 1-2 times, 10.3% 3-10 times, and 9.1% monthly. The
      proportion of monthly BSE was above 20% in Nigeria and Laos and below 2% in
      Bangladesh, India, Singapore, Russia, and South Africa. Logistic regression found
      that BSE importance or positive attitude was highly associated with BSE practice.
      BSE practices were found to be inadequate and efforts should be made to develop
      programmes that can increase knowledge related to breast cancer as well as the
      practice of breast self-examination. 

PMID- 25374182
TI  - Association of breast cancer with sleep pattern--a pilot case control study in a
      regional cancer centre in South Asia.
AB  - The rising trend of breast cancer both in developed and developing countries is a
      real threat challenging all efforts to screening, prevention and treatment
      aspects to reduce its impact. In spite of modern preventive strategies, the
      upward trend of breast cancer has become a matter of great concern in both
      developed and developing countries. Chittaranjan National Cancer Institute is a
      premier regional cancer institute in eastern region of India catering to a large
      number of cancer patients every year. A pilot case control study of fifty breast
      cancer patients and 100 matched controls was conducted during 2013 to evaluate
      the effects of habitual factors like working in night shift, not having adequate
      sleep, and not sleeping in total darkness on breast cancer of women. The study
      revealed that not sleeping in total darkness was associated with higher odds of
      outcome of breast cancer of women. This positive correlation can play a vital
      role in formulation of preventive strategies through life style modification. 

PMID- 25374183
TI  - Ovarian Malignancy Probability Score (OMPS) for appropriate referral of adnexal
      masses.
AB  - BACKGROUND: Ovarian cancer is the most common cancer cause of gynecologic cancer
      deaths. In order to increase the likelihood of patient survival through primary
      operation by gyneco-oncologists, an appropriate algorithm for referral is
      considered here. MATERIALS AND METHODS: Suspicious adnexal mass cases including
      ovarian malignancy probability score-1 (OMPS1) scores between 2.3-3.65 are re
      evaluated by OMPS2. Sensitivity and specificity of each score were determined.
      RESULTS: Sensitivity and specificity with a 3.82 score of OMPS2 in the studied
      subgroup (OMPS1 scores between 2.3-3.65) were 64% and 76.9% respectively.
      CONCLUSIONS: Management of OMPS1 scores of below 2.3 with sensitivity of 100% and
      above 3.65 with specificity of 72.9% is clear. In the subgroup of cases with
      OMPS1 score between 2.3-3.65, OMPS2 is helpful for triage with a cutoff score of
      3.82.

PMID- 25374184
TI  - Expression of Ang-2/Tie-2 and PI3K/AKT in colorectal cancer.
AB  - PURPOSE: To study the expression of angiogenin-2 (Ang-2) and its receptor Tie-2
      in colorectal cancer and discuss the possible mechanisms behind this process.
      MATERIALS AND METHODS: Using the streptavidin-peroxidase (SP) immunohistochemical
      method, paraffin sections from 100 colorectal cancer samples and 10 samples from
      tumor-adjacent normal tissue (>2 cm from the edge of the gross tumor) were tested
      for protein expression of Ang-2, Tie-2, PI3K, and AKT. Reverse transcription
      polymerase chain reaction and Western blots were further used to measure
      expression of the 4 genes and proteins in 20 freshly-resected colorectal cancer
      samples and tumor-adjacent normal tissues. RESULTS: In colorectal cancer tissues,
      the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins was
      significantly higher than in tumor-adjacent normal tissues. Protein expression in
      poorly-differentiated adenocarcinoma was higher than that in well and moderately
      differentiated adenocarcinoma. According to Duke's classification, the protein
      expression in Stages C and D was significantly higher than that in Stages A and
      B. In the group with lymphatic metastasis, the protein expression was higher than
      that without lymphatic metastasis. CONCLUSIONS: In colorectal cancer, the
      expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins is
      markedly higher than those in tumor-adjacent normal tissues. No correlation was
      observed between protein expression and gender, location, or histologic type.
      Correlations did exist between protein expression and differentiation level,
      stage of Duke's classification, and lymphatic metastasis; in colorectal cancer
      tissues with lower differentiation levels, higher stages of Duke's
      classification, and lymphatic metastasis, the expression of all 4 proteins was
      higher. The study of their expression patterns and relationships with aggression
      and metastasis will provide a valuable experimental foundation for assessing
      prognosis and targeted therapy of colorectal cancer.

PMID- 25374185
TI  - Association between dietary behavior and esophageal squamous cell carcinoma in
      Yanting.
AB  - BACKGROUND: Yanting is one of high risk areas for esophageal cancer and the
      screening program was therefore initiated there. This study was aimed to
      investigate the dietary behaviors on the risk of esophageal squamous cell
      carcinoma (ESCC), among the individuals with normal and abnormal esophagus
      mucosa. MATERIALS AND METHODS: A frequency matched case-controls study was
      proposed to estimate the different distribution of dietary behavior between
      individuals of control, esophagitis and cancer groups. Cancer cases were selected
      from hospitals. Esophagitis cases and controls were selected from screening
      population for ESCC. Health workers collected data for 1 year prior to interview,
      in terms of length of finishing a meal, temperature of eaten food and interval
      between water boiling and drinking. Chi-square, Kruskal-Wallis tests and
      unconditional logistic regression model were used to estimate differences and
      associations between groups. RESULTS: Compared with controls, length of finishing
      a meal>=15 mins was related to a reduced OR for cancer (OR=0.46, 95%CI, 0.22-
      0.97) and even compared with cases of esophagitis, the OR of cancer was reduced
      to 0.30 (95%CI, 0.13-0.72). The OR for often eating food at a high temperature
      was 2.48 (95%CI 1.06, 5.82) for ESCC as compared with controls. Interval between
      water boiling and drinking of >=10 mins was associated with lower risk of cancer:
      the OR was 0.18 compared with controls and 0.49 with esophagitis cases (p<0.05).
      CONCLUSIONS: Length of eating food>=15 mins and interval between water boiling
      and drinking >=10 mins are potentially related to reduced risk of esophageal SCC,
      compared with individuals with normal and abnormal esophageal mucosa.
      Recommendations to Yanting residents to change their dietary behaviors should be
      made in order to reduce cancer risk.

PMID- 25374186
TI  - Modified docetaxel and cisplatin in combination with capecitabine (DCX) as a
      first-line treatment in HER2-negative advanced gastric cancer.
AB  - BACKGROUND: Docetaxel and cisplatin in combination with fluorouracil (DCF)
      regimen is accepted to be one of the standard regimens in the treatment of
      advanced gastric cancer. However, substantial toxicity has limited its use in
      daily clinical practice. Therefore, modification of DCF regimens, including
      introduction of capecitabine has been investigated to improve the safety
      profiles. In the present study, the efficacy and toxicity of a regimen with a
      modified dose of docetaxel and cisplatin in combination with oral capecitabine
      (DCX) was evaluated in untreated patients with HER2-negative advanced gastric
      cancer. MATERIALS AND METHODS: Fifty-four patients with HER2-negative locally
      advanced or metastatic gastric cancer were included in this cohort. Patients
      received docetaxel 60 mg/m2 plus cisplatin 60 mg/m2 (day 1) combined with
      capecitabine 1650 mg/m2 (days 1-14) every 3 weeks. Treatment response, survival,
      and toxicity were retrospectively analyzed. RESULTS: The median age was 54 years
      (range: 24-76). The majority of patients (70%) had metastatic disease, while 11
      patients (21%) had recurrent disease and underwent curative gastrectomy, and 5
      patients (9%) had locally advanced disease (LAD). The median number of DCX cycles
      was 4. There were 28 partial responses and 11 complete responses, with an overall
      response rate of 72%. Curative surgery could be performed in four patients among
      five with LAD. At the median follow-up of 10 months, the median progression-free
      survival (PFS) and overall survival (OS) of the entire cohort of patients were
      7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due
      to toxicity in 8 and noncompliance in 4 patients. The most common hematological
      toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54
      patients (27.7%). Febrile neutropenia was diagnosed only in two cases.
      CONCLUSIONS: DCX regimen offers prominent anti-tumor activity and considered to
      be effective first- line treatment with manageable toxicity for patients with
      HER2-negative advanced gastric cancer.

PMID- 25374187
TI  - Neoadjuvant chemoradiotherapy in non-cardia gastric cancer patients--does it
      improve survival?
AB  - BACKGROUND: Survival rates after resection of advanced gastric cancer are
      extremely poor. An increasing number of patients with gastric carcinomas (GC) are
      therefore being treated with preoperative chemotherapy. We evaluated 36 month
      survival rate of GC patients that were treated by adding a neoadjuvant
      chemoradiotherapy before gastrostomy. MATERIALS AND METHODS: Patients with stage
      II or III gastric adenocarcinomas were enrolled. The patients divided into two
      groups: (A) Neoadjuvant group that received concurrent chemoradiation before
      surgery (4,500 cGy of radiation at 180 cGy per day plus chemotherapy with
      cisplatin and 5-fluorouracil, in the first and the end four days of
      radiotherapy). Resection was attempted 5 to 6 weeks after end of
      chemoradiotherapy. (B) Adjuvant group that received concurrent chemo-radiation
      after surgical resection. RESULTS: Two (16.7%) patients out of 12 patients
      treated with neoadjuvant chemo-radiotherapy and 5 (38.5%) out of 13 in the
      surgery group survived after 36 months. These rates were not significantly
      different with per protocol and intention-to-treat analysis. The median survival
      time of patients in group A and B were 13.4 and 21.6 months , respectively, again
      not significantly different. Survival was significantly greater in patients with
      well differentiated adenocarcinoma in group B than in group A (p<0.004).
      CONCLUSIONS: According to this study we suggest surgery then chemoradiotherapy
      for patients with well differentiated gastric adenocarcinoma rather than other
      approaches. Additional studies with greater sample size and accurate matching
      relying on cancer molecular behavior are recommended.

PMID- 25374188
TI  - Tobacco (kretek) smoking, betel quid chewing and risk of oral cancer in a
      selected Jakarta population.
AB  - PURPOSE: This study aimed to determine the association between tobacco
      consumption (kretek) and betel quid chewing with oral cancer risk. MATERIALS AND
      METHODS: A total of 81 cases of oral cancers were matched with 162 controls in
      this hospital-based study. Information on sociodemographic characteristics and
      details of risk habits (duration, frequency and type of tobacco consumption and
      betel quid chewing) were collected. Association between smoking and betel quid
      chewing with oral cancer were analysed using conditional logistic regression.
      RESULTS: Slightly more than half of the cases (55.6%) were smokers where 88.9% of
      them smoked kretek. After adjusting for confounders, smokers have two fold
      increased risk, while the risk for kretek consumers and those smoking for more
      than 10 years was increased to almost three-fold. Prevalence of betel quid
      chewing among cases and controls was low (7.4% and 1.9% respectively). Chewing of
      at least one quid per day, and quid combination of betel leaf, areca nut, lime
      and tobacco conferred a 5-6 fold increased risk. CONCLUSIONS: Smoking is
      positively associated with oral cancer risk. A similar direct association was
      also seen among betel quid chewers.

PMID- 25374189
TI  - Anti-CSC effects in human esophageal squamous cell carcinomas and Eca109/9706
      cells induced by nanoliposomal quercetin alone or combined with CD 133 antiserum.
AB  - CD133 was recently reported to be a cancer stem cell and prognostic marker.
      Quercetin is considered as a potential chemopreventive agent due to its
      involvement in suppression of oxidative stress, proliferation and metastasis. In
      this study, the expression of CD133/CD44 in esophageal carcinomas and Eca109/9706
      cells was explored. In immunoflurorescence the locations of CD133+ and multidrug
      resistance 1 (MDR 1)+ in the same E-cancer cells were coincident, mainly in
      cytomembranes. In esophageal squamous cell carcinomas detected by double/single
      immunocytochemistry, small CD133+ cells were located in the basal layer of
      stratified squamous epithelium, determined as CSLC (cancer stem like cells);
      CD44+ surrounding the cells appeared in diffuse pattern, and the larger CD44+
      (hi) cells were mainly located in the prickle cell layer of the epithelium, as
      progenitor cells. In E-cancer cells exposed to nanoliposomal quercetin (nLQ with
      cytomembrane permeability), down-regulation of NF-kappaBp65, histone deacetylase
      1 (HDAC1) and cyclin D1 and up-regulation of caspase-3 were shown by
      immunoblotting, and attenuated HDAC1 with nuclear translocation and promoted E
      cadherin expression were demonstrated by immunocytochemistry. In particular,
      enhanced E-cadherin expression reflected the reversed epithelial mesenchymal
      transition (EMT) capacity of nLQ, acting as cancer attenuator/preventive agent.
      nLQ acting as an HDAC inhibitor induced apoptotic cells detected by TUNEL assay
      mediated via HDAC-NF-kappaB signaling. Apoptotic effects of liposomal quercetin
      (LQ, with cytomembrane-philia) combined with CD133 antiserum were also detected
      by CD133 immunocytochemistry combined with TUNEL assay. The combination could
      induce greater apoptotic effects than nLQ induced alone, suggesting a novel anti
      CSC treatment strategy. 

PMID- 25374190
TI  - Preliminary research on the expression, purification and function of the
      apoptotic fusion protein, Sival.
AB  - The objective of the present study was to investigate cloning, expression, and
      functions of the recombinant protein, Siva1. Siva1 gene was synthesized by RT-PCR
      from HCT116 cells. Plasmids were cleaved with the restriction endonuclease,
      BamH1/Sal1 and products were connected to pQE30, which underwent cleavage by
      BamH1/Sal1. The recombinant plasmid, pQE30-Siva1, was identified after digestion
      with restriction endonucleases followed by transformation into E. coli M15.
      Expression of Siva1 was induced by IPTG and identified by SDS- PAGE following
      purification with affinity chromatography. The results showed that size of Siva1
      was 12 kDa, consistent with the molecular weight of the His-Siva1 fusion protein.
      Functional test demonstrated that Siva1 significantly inhibited the invasion and
      migration of HCT116 cells. It may thus find clinical application for control of
      cancers. 

PMID- 25374191
TI  - Cervical cancer trends in Mexico: incidence, mortality and research output.
AB  - PURPOSE: To evaluate the recent incidence and mortality of and scientific
      research trends in cervical cancer in Mexican females. MATERIALS AND METHODS:
      Data between 2000 and 2010 from the Department of Epidemiology of the Ministry of
      Health, and International Agency for Research on Cancer (IARC) of World Health
      Organization were analyzed, and age-standardized rates (ASRs) were calculated. In
      addition, scientific research data were retrieved from the Web of Science
      database from 2003 to 2012, using different terms related to cervical cancer.
      RESULTS: The incidence rate decreased during last five years, while mortality
      rates showed an annual decrease of 4.93%. A total of 780 articles were retrieved,
      and the institutions with the majority of publications were National Autonomous
      University of Mexico (34.87%), Social Security Mexican Institute (16.02%), and
      National Institute of Cancerology (15%). The main types of research were
      treatment, diagnosis, and prevention. CONCLUSIONS: The above results show that
      incidence of cervical cancer decreased over time in Mexico during last five
      years; similarly, the downturn observed in mortality mainly reflects improved
      survival as a result of earlier diagnosis and cancer treatment. Also, this
      article demonstrates the usefulness of bibliometrics to address key evaluation
      questions and to establish priorities, define future areas of research, and
      develop cervical cancer control strategies in Mexico.

PMID- 25374192
TI  - Comparison of inhibitory effect of 17-DMAG nanoparticles and free 17-DMAG in
      HSP90 gene expression in lung cancer.
AB  - BACKGROUND: Up-regulation of hsp90 gene expression occurs in numerous cancers
      such as lung cancer. D,L-lactic-co-glycolic acid-poly ethylene glycol-17
      dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and
      free 17-DMAG may inhibit the expression. The purpose of this study was to examine
      whether nanocapsulating 17DMAG improves the anti cancer effect over free 17DMAG
      in the A549 lung cancer cell line. MATERIALS AND METHODS: Cells were grown in
      RPMI 1640 supplemented with 10% FBS. Capsulation of 17DMAG is conducted through
      double emulsion, then the amount of loaded drug was calculated. Other properties
      of this copolymer were characterized by Fourier transform infrared spectroscopy
      and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity on
      the grown of lung cancer cell line was carried out through MTT assay. After
      treatment, RNA was extracted and cDNA was synthesized. In order to assess the
      amount of hsp90 gene expression, real-time PCR was performed. RESULTS: In regard
      to the amount of the drug load, IC50 was significant decreased in
      nanocapsulated(NC) 17DMAG in comparison with free 17DMAG. This was confirmed
      through decrease of HSP90 gene expression by real-time PCR. CONCLUSIONS: The
      results demonstrated that PLGA-PEG-17DMAG complexes can be more effective than
      free 17DMAG in down-regulating of hsp90 expression by enhancing uptake by cells.
      Therefore, PLGA-PEG could be a superior carrier for this kind of hydrophobic
      agent.

PMID- 25374193
TI  - Incidental abnormal FDG uptake in the prostate on 18-fluoro-2-deoxyglucose
      positron emission tomography-computed tomography scans.
AB  - 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F
      FDG PET/CT) scans are commonly used for the staging and restaging of various
      malignancies, such as head and neck, breast, colorectal and gynecological
      cancers. However, the value of FDG PET/CT for detecting prostate cancer is
      unknown. The aim of this study was to evaluate the clinical value of incidental
      prostate 18F-FDG uptake on PET/CT scans. We reviewed 18F-FDG PET/CT scan reports
      from September 2009 to September 2013, and selected cases that reported
      focal/diffuse FDG uptake in the prostate. We analyzed the correlation between 18F
      FDG PET/CT scan findings and data collected during evaluations such as serum
      prostate-specific antigen (PSA) levels, digital rectal examination (DRE),
      transrectal ultrasound (TRUS), and/or biopsy to confirm prostate cancer. Of a
      total of 18,393 cases, 106 (0.6%) exhibited abnormal hypermetabolism in the
      prostate. Additional evaluations were performed in 66 patients. Serum PSA levels
      were not significantly correlated with maximum standardized uptake values
      (SUVmax) in all patients (rho 0.483, p=0.132). Prostate biopsies were performed
      in 15 patients, and prostate cancer was confirmed in 11. The median serum PSA
      level was 4.8 (0.55-7.06) ng/mL and 127.4 (1.06-495) ng/mL in the benign and
      prostate cancer groups, respectively. The median SUVmax was higher in the
      prostate cancer group (mean 10.1, range 3.8-24.5) than in the benign group (mean
      4.3, range 3.1-8.8), but the difference was not statistically significant
      (p=0.078). There was no significant correlation between SUVmax and serum PSA,
      prostatic volume, or Gleason score. 18F-FDG PET/CT scans did not reliably
      differentiate malignant or benign from abnormal uptake lesions in the prostate,
      and routine prostate biopsy was not usually recommended in patients with abnormal
      FDG uptake. Nevertheless, patients with incidental prostate uptake on 18F-FDG
      PET/ CT scans should not be ignored and should be undergo further clinical
      evaluations, such as PSA and DRE. 

PMID- 25374194
TI  - Association between the TGFBR2 G-875A polymorphism and cancer risk: evidence from
      a meta-analysis.
AB  - Disrupted transforming growth factor- beta (TGF-beta) signaling is involved in
      the development of various types of cancer and the TGF-beta receptor II (TGFBR2)
      is a key mediator of TGF-beta growth inhibitory signals. It is reported that the
      G-875A polymorphism in TGFBR2 is implicated in risk of various cancers. However,
      results for the association between this polymorphism and cancer remain
      conflicting. To derive a more precise estimation, a meta-analysis of 3,808 cases
      and 4,489 controls from nine published case-control studies was performed. Our
      analysis indicated that G-875A is associated with a trend of decreased cancer
      risk for allele A versus(vs.) allele G [odds ratio (OR) =0.64, 95% confidence
      intervals (CI): 0.55-0.74], as well as for both dominant model [(A/ A+G/A) vs.
      G/G, OR=0.76, 95% CI: 0.64-0.90] and recessive model [A/A vs. (G/G+G/A), OR=0.74,
      95% CI: 0.59-0.93). However, larger scale primary studies are required to further
      evaluate the interaction of TGFBR2 G-875A polymorphism and cancer risk in
      specific cancer subtypes. 

PMID- 25374195
TI  - Meta-analysis of associations between interleukin-17 gene polymorphisms and risk
      of gastric cancer.
AB  - BACKGROUND: Previous studies have indicated that single nucleotide polymorphisms
      (SNPs) of the interleukin-17 (IL-17) gene are associated with an increased risk
      of gastric cancer. However, the findings were inconsistent. MATERIALS AND
      METHODS: To provide a more reliable estimation of the association between SNPs in
      the IL-17 gene and the susceptibility to gastric cancer, we searched PubMed,
      CNKI, and Wan Fang databases and selected finally six studies covering 2,366
      cases and 3,205 controls to perform a meta-analysis. RESULTS: Statistical
      analyses showed that an rs2275913 polymorphism within the IL-17A gene was
      significantly associated with an increased risk of gastric cancer using a
      generalized odds ratio (ORG, a model-free approach). Moreover, we also found that
      the 'A' allele carriers of IL-17A rs2275913 had a significant link with
      clinicopathological features. However, no significant positive signals were
      observed in the association analysis of the rs3748067 and rs763780 polymorphisms
      with the risk of gastric cancer in IL-17A and IL-17F, respectively. CONCLUSIONS:
      Despite some limitations, the present meta-analysis provided a more precise
      estimation of the relationship between the IL-17 gene SNPs and gastric cancer
      risk compared with individual studies.

PMID- 25374196
TI  - Efficacy and safety of first line vincristine with doxorubicin, bleomycin and
      dacarbazine (ABOD) for Hodgkin's lymphoma: a single institute experience.
AB  - BACKGROUND: ABVD (doxorubicin, bleomycin, vinblastine (Vb) and dacarbazine) is
      the standard regimen in Hodgkin's lymphoma (HL).Vincristine (O) is a mitotic
      spindle agent like Vb. We aimed to evaluate the efficacy and safety of O as a
      part of ABOD in HL. MATERIALS AND METHODS: Patients who had ABOD were enrolled.
      Stage I-II HL were evaluated for unfavorable risk factors according to NCCN.
      National Cancer Institute Common Toxicity Criteria was used for toxicity.
      RESULTS: Seventy-nine HL patients in our center between 2003 and 2007 were
      evaluated retrospectively. Median follow-up was 54 months. Most of the patients
      were male in their third decade. Median ABOD cycles were 6 (2-8). Primary
      refractory disease rate was 17.7% whereas it was 5.1% for early relapse and 5.1%
      for late relapse disease. Response rates were as 82.3% for complete response,
      11.4% for partial response, 5.1% for stable disease and 1.3% for progressive
      disease. Half of relapsed patients had autologous stem cell transplantation.
      Estimated 5-year failure-free survival was 71% and significantly longer in early
      stage patients without risk factors, bulky disease or radiotherapy (RT) (p=0.05,
      p<0.0001, p=0.02; respectively). Estimated 5-year overall survival was 74% and
      significantly longer in those who had no RT (p=0.001). Dose modification rate was
      5.1% and chemotherapy delay rate was 19%. There were no toxicity- related deaths.
      CONCLUSIONS: ABOD seems to be effective with managable toxicity in HL, even in
      those with poor prognostic factors.

PMID- 25374197
TI  - Attitudes of South Asian women to breast health and breast cancer screening:
      findings from a community based sample in the United States.
AB  - BACKGROUND: Breast cancer incidence is increasing among South Asian migrants to
      the United States (US). However, their utilization of cancer screening services
      is poor. This study characterizes attitudes of South Asians towards breast health
      and screening in a community sample. MATERIALS AND METHODS: A cross-sectional
      survey based on the Health Belief Model (HBM) was conducted among South Asians
      (n=124) in New Jersey and Chicago. The following beliefs and attitudes towards
      breast cancer screening were assessed-health motivation, breast self-examination
      confidence, breast cancer susceptibility and fear, and mammogram benefits and
      barriers. Descriptive statistics and Spearman rank correlation coefficients were
      computed for HBM subscales. FINDINGS: Mean age of participants was 36 years with
      an average 10 years stay in the US. Most women strived to care for their health
      (3.82+/-1.18) and perceived high benefits of screening mammography (3.94+/-0.95).
      However, they perceived lower susceptibility to breast cancer in the future
      (2.30+/-0.94). CONCLUSIONS: Increasing awareness of breast cancer risk for South
      Asian women may have a beneficial effect on cancer incidence because of their
      positive attitudes towards health and breast cancer screening. This is especially
      relevant because South Asians now constitute one of the largest minority
      populations in the US and their incidence of breast cancer is steadily
      increasing.

PMID- 25374198
TI  - No association of the TGF-beta1 29T/C polymorphism with breast cancer risk in
      Caucasian and Asian populations: evidence from a meta-analysis involving 55,841
      subjects.
AB  - The transforming growth factor-beta1 (TGF-beta1) gene 29 T/C polymorphism is
      thought to be associated with breast cancer risk. However, reports are largely
      conflicting and underpowered. We therefore conducted a meta- analysis of all
      available case-control studies relating the TGF-beta1 29T/C polymorphism to the
      risk of developing breast cancer by including a total of 31 articles involving
      24,021 cases and 31,820 controls. Pooled ORs were generated for the allele
      contrasts, with additive genetic, dominant genetic and recessive genetic models.
      Subgroup analysis was also performed by ethnicity for the TGF-beta1 29T/C
      polymorphism. No association was found in the overall analysis (C vs T: OR=1.028,
      95% CI=0.949-1.114, p-value 0.500; CC vs TC: OR=1.022, 95% CI=0.963- 1.085, p
      value 0.478; CC vs TT: OR=1.054, 95% CI=0.898-1.236, p-value 0.522; CC vs TT+TC:
      OR=1.031, 95% CI=0.946-1.124, p-value 0.482; TT vs CC+TC: OR=0.945, 95% CI=0.827
      1.080, p-value 0.403). Similarly, in the subgroup analysis by ethnicity, no
      association was found in Caucasian (C vs T: OR=1.041, 95% CI=0.932-1.162, p-value
      0.475; CC vs TC: OR=1.031, 95% CI=0.951-1.118, p-value 0.464; CC vs TT: OR=1.081,
      95% CI=0.865- 1.351, p-value 0.493; CC vs TT+TC: OR=1.047, 95% CI=0.929-1.180, p
      value 0.453; TT vs CC+TC: OR= 0.929, 95% CI=0.775-1.114, p-value 0.429;) and
      Asian populations (C vs T: OR=1.004, 95% CI=0.908-1.111, p-value 0.931; CC vs TC:
      OR= 0.991, 95% CI=0.896-1.097, p-value 0.865; CC vs TT: OR=1.015, 95% CI=0.848
      1.214, p-value 0.871; CC vs TT+TC: OR=1.000, 95% CI=0.909-1.101, p-value 0.994;
      TT vs CC+TC: OR= 0.967, 95% CI=0.808-1.159, p-value 0.720;). No evidence of
      publication bias was detected during the analysis. No significant association
      with breast cancer risk was demonstrated overall or on subgroup (Caucasian and
      Asian) analysis. It can be concluded that TGF-beta1 29T/C polymorphism does not
      play a role in breast cancer susceptibility in overall or ethnicity-specific
      manner.

PMID- 25374199
TI  - Status and determinants of health literacy among adolescents in Guangdong, China.
AB  - BACKGROUND: Previous studies for non-communicable disease cotrol, including
      cancer, have mostly relied on health literacy in adults. However, limited studies
      are available for adolescents. This study aimed to assess the status and
      determinants of health literacy in in-school adolescents in Guangdong, China.
      MATERIALS AND METHODS: A total of 3,821 students aged 13-25 years were selected
      by multi-stage cluster sampling. After the questionnaire of health literacy was
      answered, the total scores for health knowledge (18 questions), skills (5
      questions) and behaviors (14 questions) were determined. The total scores for
      health literacy and each subscale were recoded into adequate and inadequate
      subgroups, and logistic regression models were used to identify factors
      associated with each outcome variable. RESULTS: The prevalence of adequate health
      literacy was 14.4%, and the prevalences for adequate knowledge, skills and
      behavior were 22.4%, 64.7% and 6.6%, respectively. Students coming from
      prestigious schools and having parents with higher education had higher odds of
      having adequate knowledge, skills and behaviors. Female students had higher odds
      of having adequate knowledge and behaviors. Students in grade 7-8 had higher odds
      of having adequate knowledge and skills. The health knowledge was positive
      associated with health skills (odds ratio [OR]=2.1, 95% confidence interval [CI]
      1.7-2.5) and behaviors (OR=3.0, 95% CI 2.3-4.0), and health skills were positive
      associated with health behaviors (OR=2.6, 95% CI 1.8-3.8). CONCLUSIONS: Further
      efforts should be made to increase adolescents' health knowledge and behaviors,
      especially for low grade and male students in non-prestigious schools.

PMID- 25374200
TI  - Genetic polymorphism of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor
      antagonist (IL-1RN) and prostate cancer risk.
AB  - PURPOSE: We aimed to investigate the associations between polymorphisms of
      interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate
      cancer (PCa) risk. MATERIALS AND METHODS: A comprehensive search for articles of
      MEDLINE and EMBASE databases and bibliographies of retrieved articles published
      up to August 3, 2014 was performed. Methodological quality assessment of the
      trials was based on a standard quality scoring system. The meta-analysis was
      performed using STATA 12.0. RESULTS: We included 9 studies (1 study for IL-1A, 5
      studies for IL-1B, and 3 studies for IL-1RN), and significant association was
      found between polymorphisms of IL-1B-511 (rs16944) as well as IL-1B-31
      (rs1143627) and PCa risk. IL-1B-511 (rs16944) polymorphism was significantly
      associated with PCa risk in homozygote and recessive models, as well as allele
      contrast (TT vs CC: OR, 0.74; 95%CI, 0.58-0.94; P=0.012; TT vs TC+CC; OR, 0.79;
      95%CI, 0.63-0.98; P=0.033; T vs C: OR, 0.86; 95%CI, 0.77-0.96; P=0.008). The
      association between IL-1B-31 (rs1143627) polymorphism and PCa risk was weakly
      significant under a heterozygote model (OR, 1.35; 95%CI, 1.00-1.80; P=0.047).
      CONCLUSIONS: Sequence variants in IL-1B-511 (rs16944) and IL-1B-31 (rs1143627)
      are significantly associated with PCa risk, which provides additional novel
      evidence that proinflammatory cytokines and inflammation play an important role
      in the etiology of PCa.

PMID- 25374201
TI  - Follow-up consultations for cervical cancer patients in a Mexican cancer center.
      Comparison with NCCN guidelines.
AB  - PURPOSE: This study aimed to determine the patterns of follow-up visits for
      cervix cancer in a national cancer center in Mexico. MATERIALS AND METHODS: The
      National Cancer Institute of Mexico is cancer center with 119 beds that mostly
      cares for an underserved and socially disadvantaged population. The medical
      records of cases of cervical cancer that had at least one year of clinical follow
      up after being in complete response at the end of primary treatment were
      analyzed. We recorded the numbers of total and yearly follow-up visits and these
      were compared with the number of follow-up visits recommended by the National
      Comprehensive Cancer Network 2013, version 2 for cervical cancer. RESULTS:
      Between March and June 2007, the medical records of 96 consecutive patients were
      reviewed. Twenty (21%) of these met inclusion criteria and were selected. In the
      first year the median number of visits was 11 (4-20). In the ensuing years, 2nd,
      3rd, 4th and 5th, the number of analyzed patients remaining in follow-up
      decreased to 17, 14, 13 and 9 respectively. There were 462 follow-up visits to
      primary treating services (Gynecology Oncology, Radiation Oncology and Medical
      Oncology) as compared to 220 suggested by the NCCN guidelines (X2 test p<0.0001).
      There were 150 additional visits to other services. CONCLUSIONS: Our results
      suggest that in our institution there is an overuse of oncological services by
      cervical cancer patients once treatment is completed.

PMID- 25374202
TI  - Glioma epidemiology in the central Tunisian population: 1993-2012.
AB  - BACKGROUND: Glioma is a heterogeneous central nervous system (CNS) tumor group
      that encompasses different histological subtypes with high variability in
      prognosis. The lesions account for almost 80% of primary malignant brain tumors.
      The aim of this study is to extend our understanding of the glioma epidemiology
      in the central Tunisian region. MATERIALS AND METHODS: We analyzed 393 gliomas
      recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence
      rates (CR) and world age-standardized rates (ASR) were estimated using annual
      population data size and age structure. Statistic correlations were established
      using Chi-square and Kaplan-Meier test. RESULTS: Tunisian glioma patients were
      identified with a mean age at diagnosis of 48 years and 1.5 sex ratio
      (male/female). During the 19 years period of study the highest incidence value
      was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence
      results underline increasing high grade glioma occurring in the adulthood in the
      last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year
      survival rates of 42%, 30% and 26%, respectively. Survival was greater in
      patients with younger age, lower tumor grade, infratentrial tumor location and
      undergoing a palliative treatment. CONCLUSIONS: This central Tunisia gliomas
      registry study provides important information that could improve glioma
      management and healthcare practice.

PMID- 25374203
TI  - Distribution of Ki67 proliferative indices among WHO subtypes of non-Hodgkin's
      lymphoma: association with other clinical parameters.
AB  - BACKGROUND: Non-hodgkin lymphoma (NHL) is a diverse group of disease encompassing
      divergent tumor types with contrasting clinical behaviors. We aimed to evaluate
      the usefulness of Ki67 index in segregating indolent from aggressive NHL and its
      association with clinical parameters. MATERIALS AND METHODS: During a study
      period of 4.5 years, a total of 215 cases of lymphomas were diagnosed among of
      which 172 cases were NHL. Ki67 immunohistochemical staining was performed by the
      DAKO envision method. Average proportion of tumor cells stained was calculated to
      determine the proliferative index. RESULTS: The mean age at diagnosis was 46.2
      years +19.8 (3-81) with a male to female ratio of 1.5:1. Mean Ki67 index for
      indolent NHL included 23% for small cell, 25% for mantle cell, 28.5% for marginal
      zone and 34.6% for follicular lymphoma. On the other hand, mean Ki67 index for
      aggressive lymphomas were 66.4%, 66.9%, 80.3%, 83.3% and 94.4% for diffuse large
      B cell, T cell (NOS), anaplastic large cell, lymphoblastic and burkitts lymphoma
      respectively. No significant correlation was found between Ki67 index and other
      clinical parameters like age and extra nodal involvement. CONCLUSIONS: Ki67 index
      is a valuable IHC marker to distinguish indolent from aggressive lymphomas
      especially in small needle biopsies where exact typing may not be possible.

PMID- 25374204
TI  - Association of risk of gastric cancer and consumption of tobacco, alcohol and tea
      in the Chinese population.
AB  - This study aimed at summarizing epidemiological research findings on associations
      between tobacco, alcohol and tea consumption and risk of gastric cancer (GC) in
      the Chinese population. The review searched PubMed, Embase, China National
      Knowledge Infrastructure (CNKI) and China Biology Medicine (CBM) databases and
      reference lists of review papers for all studies published in English or Chinese
      languages. Information extracted, via two independent researchers, from retrieved
      articles included first author, year of publication, study design, sample size,
      source of controls and adjusted odds ratio (OR) or relative risk (RR) with the
      corresponding 95% confidence intervals (CIs) for each category. Statistical
      analyses used software STATA version 12.0. The systematic search found 89
      articles containing 25,821 GC cases and 135,298 non-cases. The overall random
      effects in terms of pooled OR and 95%CI for tobacco, alcohol and tea consumption
      were 1.62 (95%CI: 1.50-1.74), 1.57 (95%CI: 1.41-1.76) and 0.67 (95%CI: 0.59-0.76)
      respectively; while the heterogeneity among included studies ranged from 80.1% to
      87.5%. The majority of subgroup analyses revealed consistent results with the
      overall analyses. All three behavioral factors showed statistically significant
      dose-dependent effects on GC (P<0.05). The study revealed that tobacco smoking
      and alcohol drinking were associated with over 1/2 added risk of GC, while tea
      drinking conferred about 1/3 lower risk of GC in the Chinese population. However,
      these results should be interpreted with caution given the fact that most of the
      included studies were based on a retrospective design and heterogeneity among
      studies was relatively high. 

PMID- 25374205
TI  - Association between polymorphisms of interleukin-17A and interleukin-17F genes
      and silicosis susceptibility in Chinese Han people.
AB  - BACKGROUND: To explore the relationship between polymorphisms of interleukin17
      (IL-17) gene(A-832G 7488A/G) and the susceptibility to silicosis, a risk factor
      for lung cancer. MATERIALS AND METHODS: A total of 113 silicosis patients and 116
      workers without silicosis were enrolled in the case-control study. IL-17A A-832G
      and IL-17F 7488A/G polymorphisms were evaluated by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of
      AA,GG and AG of IL-17A A-832G locus in the case and control groups were 46.9%,
      8.0%, 45.1%, and 49.2%, 7.6%, 43.2%, respectively, with no significant
      differences (p>0.05).The GG genotype in the IL-17F (7488A/G) locus was not found.
      The frequencies of AA and GA of IL-17F 7488A/G locus in the case and control
      groups were 84.1%, 15.9% and 66.4%, 33.6%, respectively (p<0.05). Analysis of
      combined effects showed that the individuals with GG+AG genotype of IL-17A and
      GG+GA genotype of IL-17F are protected against silicosis (OR=0.469). CONCLUSIONS:
      IL-17F 7488A/G is associated with susceptibility to silicosis, and G allele may
      have a protective effect. No relationship was found between IL-17A gene
      polymorphisms at A-832G and silicosis.

PMID- 25374206
TI  - Epidemiology of female reproductive cancers in Iran: results of the Gholestan
      Population-based Cancer Registry.
AB  - BACKGROUND: Malignancies of the female reproductive tract are estimated to be the
      third most common group of cancers in women. OBJECTIVES: We here aimed to present
      their epidemiological features in Golestan province located in Northeast of Iran.
      MATERIALS AND METHODS: Data on primary female reproductive cancers diagnosed
      between 2004-2010 were obtained from Golestan Population-based Cancer Registry
      (GPCR). CanReg-4 and SPSS software were used for data entry and analysis. Age
      standardized incidence rates (ASR) (per 100,000 person-years) were calculated
      using the world standard population. Poisson regression analysis was used to
      compare incidence rates. P-values of less than 0.05 were considered as
      significant. RESULTS: A total of 6,064 cancer cases were registered in Golestan
      females in the GPCR during 2004-2010, of which 652 cases (11%) were female
      reproductive cancers. Cancers of the ovary (ASR=6.03) and cervix (ASR=4.97) were
      the most common. We found significant higher rates in females living in cities
      than in villages. Our results showed a rapid increase in age specific incidence
      rates of female reproductive cancers at the age of 30 years. CONCLUSIONS: We
      found significant higher rates of female reproductive cancers among residents of
      cities than villages. Differences in the prevalence of risk factors including
      reproductive behavior between the two populations may partly explain such
      diversity. Our results also showed a rapid increase in incidence rates of these
      cancers in young age females. Further studies are warranted to determine risk
      factors of female reproductive cancers in our population.

PMID- 25374207
TI  - Factors affecting the quality of life of Korean cancer survivors who return to
      the workplace.
AB  - BACKGROUND: Although the prevalence of cancer is increasing, it is no longer
      synonymous with death. The number of cancer survivors is estimated to be
      increasing due to development in medical treatments and social programs; cancer
      survivors are increasingly returning to work after long-term unemployment. Thus,
      we examined the quality of life (QOL) and the factors associated with return of
      cancer survivors to the workplace. MATERIALS AND METHODS: This study was
      performed using the 2008 Community Health Survey administered by the Korea
      Centers for Disease Control and Prevention (N=548). We used Chi-square tests to
      compare demographic variables based on self-perceived health status, and analysis
      of variance (ANOVA) to compare QOL scores among groups. We also performed a mixed
      model analysis of the relationship between QOL and factors at the workplaces of
      cancer survivors. RESULTS: Based on the results of our study, the overall QOL of
      cancer survivors was associated with 'mutual respect', 'free emotional
      expression', occupation, and age. Moreover, different trends of QOL according to
      self-perceived health were identified on additional analysis. In the 'bad' self
      perceived health group, QOL was significantly different according to income. The
      QOL of cancer survivors in the low-income group was lower than in the other
      groups. Conversely, the 'normal' group had a lower QOL caused by 'no mutual
      respect' and "no free emotional expression" in the workplace. The QOL in the
      'good' group based on self-perceived health was higher in the younger age group.
      CONCLUSIONS: There may be a significant relationship between QOL and workplace
      factors for cancer survivors, although further study is needed to investigate
      this relationship in detail. This may facilitate formulation of policy and
      efforts to prevent and manage the decline in the QOL of cancer survivors
      returning to work.

PMID- 25374208
TI  - Estrogen receptor alpha gene expression in breast cancer tissues from the Iranian
      population--a pilot study.
AB  - Estrogen receptor alpha (ERalpha) is one of the major sub-types of estrogen
      receptors. ERalpha plays an important role in cellular proliferation and
      differentiation, chiefly in mammary tissues. In the present study we aimed to
      quantify of ERalpha mRNA and protein expression in breast tissues from the
      Iranian population using a real-time PCR assay. Twenty nine breast tissues
      including 19 adenocarcinomas and 10 normal controls were recruited from the
      Iranian population. mRNA extraction and cDNA synthesis were performed from these
      tissues using commercial kits. ERalpha mRNA and protein expression was quantified
      using real-time PCR and immunohistochemistry respectively. The results showed
      high expression of ERalpha mRNA (68%) and protein (53%) in the majority of breast
      cancer tissues compared to normal breast tissues (p=0.035). Also, high ERalpha
      mRNA was associated with tumour size of breast carcinomas. In this study, we
      first reported the expression of ERalpha in Iranian patients with breast cancers
      and demonstrated prevalence of the expression to be similar to breast cancers
      noted in other populations.

PMID- 25374209
TI  - Influence of serum VEGF levels on therapeutic outcome and diagnosis/prognostic
      value in patients with cervical cancer.
AB  - OBJECTIVE: To explore the influence of serum vascular endothelial growth factor
      (VEGF) level on therapeutic outcome and diagnosis/prognostic value in patients
      with cervical cancer. MATERIALS AND METHODS: A total of 37 patients diagnosed
      with cervical cancer by biopsy were selected and treated with concurrent
      chemoradiotherapy. Double-antibody sandwich enzyme-linked immunosorbent assay
      (ELISA) was adopted before treatment to assess VEGF levels, and its relationships
      with clinicopathological features and short-term therapeutic effects were
      analyzed. RESULTS: The median VEGF level in 37 patients before treatment was
      647.15 (393.35~1125.16) pg/ mL. Serum VEGF levels in patients aged <50 years, in
      International Federation of Gynecology and Obstetrics (FIGO) stage IIIa~IVa, with
      lymph node metastasis and tumor size>4 cm were significantly increased (P<0.05).
      The complete remission (CR) rate was 48.7% (18/37), partial remission (PR) rate
      was 35.1% (13/37), stable disease (SD) rate was 13.5% (5/37) and progressive
      disease (PD) rate was 2.70% (1/37), so the objective remission rate (ORR) after
      treatment was 83.8% (31/37). Logistic regression analysis showed that tumor size
      and serum VEGF level before treatment were independent risk factors affecting the
      therapeutic outcome, and the higher the level of serum VEGF, the worse the
      prognosis when tumor size>4 cm. Some 56.8% of patients manifested with
      myelosuppression, 37.8% with leucopenia, 24.3% with thrombocytopenia, 5.41% with
      diarrhea, 46.0% with nausea and vomiting, 21.6% with hair loss and 8.11% with
      hepatic and renal injury during the treatment. CONCLUSIONS: Serum VEGF level may
      reflect the degree of malignancy of cervical cancer and predict therapeutic
      effect, which is of great importance to cancer diagnosis and prognosis.

PMID- 25374210
TI  - Pharmacoeconomics evaluation of morphine, MS contin and oxycodone in the
      treatment of cancer pain.
AB  - OBJECTIVE: To analyze cost-effectiveness of morphine, MS contin and oxycodone in
      the treatment of cancer pain, providing guidance for rational drug use in the
      clinic. METHODS: Confirmed by histology, a total of 171 patients with various
      cancers who required analgesic treatment were selected and divided into 3 groups,
      57 cases for each group, given morphine, MS contin and oxycodone, respectively.
      If there appeared a poor short-term effect or aggravated sudden pain during the
      treatment, a short-acting morphine injection was given and adverse reactions were
      processed by symptomatic treatment. The pain relief rate and adverse reactions of
      groups were observed and pharmacoeconomics evaluation was undertaken. RESULTS:
      The pain relief rates with morphine, MS contin and oxycodone were 89.5%(51/57),
      91.2%(52/57) and 93.0%(53/57), respectively, with no difference samong groups
      (chi2=4.4489, P=0.6162). The occurrence rates of adverse reactions were
      59.7%(34/57), 54.4%(31/57) and 43.9%(25/57), again with no significant variation
      (P>0.05). The ratios of cost-effectiveness (C/E) for the 3 groups were 14.6+/
      7.21, 15.0+/-7.44 and 16.1+/-8.10. When the price of 3 kinds of analgesics was
      reduced by 10%, the ratios of cost-effectiveness were 12.2+/-6.53, (13.4+/-6.08
      and 14.5+/-6.74 but there was no differences when compared with before the price
      adjustment (t=1.86, P=0.0651; t=1.30, P=0.1948; t=1.17, P=0.2453). CONCLUSION:
      Morphine, MS contin and oxycodone give similar pain relief and adverse reaction
      rates but of all, morphine is the preferred drug for the treatment of cancer pain
      from the perspective of pharmacoeconomics.

PMID- 25374211
TI  - Knowledge, attitudes and behaviors of women over 20 years old on cervix cancer in
      Istanbul, Turkey.
AB  - PURPOSE: The aim of the study was to evaluate knowledge, attitudes and behaviors
      of Turkish women over 20 years old on cervix cancer. MATERIALS AND METHODS: This
      descriptive study was performed at a primary care center covering 246 women using
      a questionnaire composed of 3 sections and 38 questions. The data were analyzed
      using descriptive statistics, chi-square test in univariate analysis and
      multivariate hierarchical logistic regression analysis. RESULTS: Of the 93.7%
      women who knew about cervical cancer, 68.0% of them had heard pap smear test and
      46.1% had actually undergone a Pap smear once or more throughout their lives.
      According to the results of the hierarchical logistic regression analysis about
      factors affecting the Pap smear test; in Model 1, increase in age and education
      levels, in Model 2 and Model 3 increase in age and cervical cancer information
      points were determined. The most important information source for cervical cancer
      was TV-radio/media (59.9%) and health care workers (62.8%) for pap smear test.
      CONCLUSIONS: Although most women have heard of cervical cancer, knowledge about
      cervical cancer and also Pap smear screening rate are significantly lower. Having
      Pap smear test for women was affected by age and knowledge level about cervical
      cancer. Informing women about cervical cancer would be an important intervention.

PMID- 25374212
TI  - Process evaluation of the first computer tailored program for smoking cessation
      among Romanian smokers.
AB  - The objective of this paper is to present the implementation and process
      evaluation of the first computer tailored program for smoking cessation among
      Romanian smokers. The program targeted adult smokers who declared the intention
      to quit smoking in the next six months. The intervention consisted of a letter
      tailored to several respondent characteristics: gender, cognitive variables
      (attitude, social influence, and self-efficacy), intention to quit smoking, goal
      and relapse prevention strategies (action and coping plans), and smoking
      behaviour. The first 80 participants entered into the program filled in a process
      evaluation questionnaire one month after the intervention. The results of our
      study confirmed that the participants had read and remembered the letter.
      Moreover, new for Romania, this approach was positively appreciated by the
      participant and the score received for the tailored letter was high. The opinions
      of the participants confirmed that the tailored letter provided information that
      was useful, trustworthy and relevant for the individual. At the same time, the
      participants appreciated the polite, easy to understand content of the letter.
      These data underlined the premises for continuing the program and for using the
      information and communication technologies for healthy lifestyle promotion among
      Romanian population. 

PMID- 25374213
TI  - CYP2E1 genetic polymorphism with dietary, tobacco, alcohol habits, H. pylori
      infection status and susceptibility to stomach cancer in Mizoram, India.
AB  - BACKGROUND: The incidence of stomach cancer in India is highest in the state of
      Mizoram. In this population based matched case-control study, we evaluated the
      relationship between CYP450 2E1 RsaI polymorphism and risk of stomach cancer
      taking into considering various important dietary habits along with tobacco,
      alcohol consumption and H. pylori infection status. MATERIALS AND METHODS: A
      total of 105 histologically confirmed stomach cancer cases and 210 matched
      healthy population controls were recruited. CYP2E1 RsaI genotypes were determined
      by PCR-RFLP and H. pylori infection status by ELISA. Information on various
      dietary, tobacco and alcohol habits was recorded in a standard questionnaire.
      RESULTS: Our study revealed no significant association between the CYP2E1 RsaI
      polymorphism and overall risk of stomach cancer in Mizoram. However, we observed
      a non-significant protective effect of the variant allele (A) of CYP2E1 against
      stomach cancer. Tobacco smokers carrying C/C genotype have three times more risk
      of stomach cancer, as compared to non-smokers carrying C/C genotype. Both Meiziol
      and cigarette current and past smokers who smoked for more than 10 times per day
      and carrying the (C/C) genotype are more prone to develop stomach cancer. Smoke
      dried fish and preserved meat (smoked/sun dried) consumers carrying C/C genotype
      possesses higher risk of stomach cancer. No significant association between H.
      pylori infection and CYP2E1 RsaI polymorphism in terms of stomach cancer was
      observed. CONCLUSIONS: Although no direct association between the CYP2E1 RsaI
      polymorphism and stomach cancer was observed, relations with different tobacco
      and dietary risk habits in terms of developing stomach cancer exist in this high
      risk population of north-eastern part of India. Further in-depth study recruiting
      larger population is required to shed more light on this important problem.

PMID- 25374214
TI  - Treatment efficacy and prognostic factors for huge HCC based on Barcelona Clinic
      Liver Cancer staging.
AB  - OBJECTIVE: To explore the most appropriate treatment for patients with
      hepatocellular cancer (HCC)>10 cm by using the Barcelona Clinic Liver Cancer
      (BCLC) classification. MATERIALS AND METHODS: A total of 124 HCC patients
      undergoing surgery were selected. Disease-free survival (DFS), overall survival
      (OS) and prognostic factors were respectively assessed. RESULTS: This study
      showed that the cumulative 1-, 3-, 5-year survival rates were 79.7%, 59.8% and
      41.6% in BCLC-A patients, 76.2%, 9.5% and 0% in BCLC-B patients and 44.9%, 0% and
      0% in BCLC-C patients, respectively. The 1-, 3-, 5-year DFS rates were 49%, 24.5%
      and 9.1% in BCLC-A patients, 7.5%, 0% and 0% in BCLC-B patients, respectively. No
      BCLC-C patients survived 1 year after surgery. Multivariate analysis indicated
      that hepatitis B surface antigen (HBsAg), vascular invasion, intra-hepatic
      metastasis, curative resection, tumor rupture and pathologic differentiation were
      independent prognostic factors. CONCLUSIONS: Surgery is effective and safe for
      patients with HCC>10 cm with sufficient hepatic reserve.

PMID- 25374215
TI  - Targeting of COX-2 expression by recombinant adenovirus shRNA attenuates the
      malignant biological behavior of breast cancer cells.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2), considered to have tumor-promoting
      potential, is highly expressed in a variety of tumors, including breast cancer.
      Since the functions and action mechanisms of COX-2 in breast cancer have not been
      fully elucidated, in the present study, the effects of target inhibiting COX-2
      with recombinant adenovirus Ad-COX-2-shRNA on malignant biological behavior were
      investigated in representative cell lines. MATERIALS AND METHODS: Breast cancer
      MDA-MB-231 and MCF-7 cells were transfected with Ad-COX-2-shRNA and COX-2
      expression was tested by RT-PCR and Western blotting. Changes in proliferation,
      apoptosis and invasion of breast cancer cells were detected with various assays
      including MTT, colony forming, flowcytometry and Transwell invasion tests. The
      expression of related proteins involved in the cell cycle, apoptosis, invasion
      and signaling pathways was assessed by Western blotting. RESULTS: COX-2
      expression was significantly reduced in both breast cancer cell lines infected
      with Ad-COX-2-shRNA, with obvious inhibition of proliferation, colony forming
      rate, G2/M phase passage and invasion, as well as induction of apoptosis, in MDA
      MB-231 and MCF-7 cells, respectively. At the same time, proteins related to the
      cell cycle, anti-apoptosis and invasion were significantly downregulated. In
      addition, c-myc expression and phosphorylation activation of Wnt/beta-catenin and
      p38MAPK pathways were reduced by the Ad-COX-2-shRNA. CONCLUSIONS: COX-2
      expression is associated with proliferation, apoptosis and invasion of breast
      cancer cells, and its mechanisms of action involve regulating expression of c-myc
      through the p38MAPK and Wnt/beta-catenin pathways.

PMID- 25374216
TI  - Epidemiology of hepatitis C virus genotypes in northeastern Thai blood samples.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is an important cause of liver
      cancer in Thailand. The highest prevalence of anti-HCV positive among Thai blood
      donors is found in the northeastern region. The present analysis of the genotype
      distribution among anti-HCV positive northeastern-Thai blood donors was conducted
      to provide a base for the epidemiological pattern of HCV infection in this
      region. MATERIALS AND METHODS: A total of 112 HCV seropositive healthy blood
      donors were randomly selected and tested for the presence of HCV-RNA by RT-PCR.
      HCV-RNA positive samples were genotyped by direct sequencing at core region
      genomes and confirmed by phylogenetic analysis. RESULTS: HCV viremia was found in
      94.6% (106/112) of HCV seropositive blood donors. There were 3 major genotypes
      distributed among this population. HCV genotype 3a was the most prevalent (71.7%)
      followed by genotypes 1a (7.5%), 1b (7.5%), 6i (3.8%), 6f (2.8%) and 6n (1.9%).
      CONCLUSIONS: HCV genotype 3a in asymptomatic infections in northeastern Thailand
      is significantly higher than other previous reports. Subgenotype 6 prevalence is
      less than in neighboring countries and distribution patterns differ. The findings
      are relevant as predictors for using interferon therapy in this population.

PMID- 25374217
TI  - Oral cyclophosphamide and etoposide in treatment of malignant pleural
      mesothelioma.
AB  - BACKGROUND: Malignant mesothelioma (MM) is almost always fatal and few treatment
      options are available. The aim of this study was to evaluate the efficacy of oral
      cyclophosphamide and etoposide for patients who underwent standard treatment for
      advanced MM. MATERIALS AND METHODS: This study included 22 malignant pleural
      mesothelioma patients who were treated with oral cyclophosphamide and etoposide
      (EE). RESULTS: The average follow-up period of the patients was 39.1 months.
      Under the treatment of oral EE, median progression- free survival was 7.7 months
      [95%CI HR (4.3-11.1)] and median overall survival was 28.1 months [95%CI HR (5.8
      50.3)]. The treatment response rates were as follows: 4 patients (27.3%) had a
      partial response (PR), 12 (54.5%) had stable disease (SD), and progressive
      disease (PD) was observed in 6 (35.9%). CONCLUSIONS: Oral EE can be administered
      effectively to patients with inoperable malignant mesothelioma who had previously
      received standard treatments.

PMID- 25374218
TI  - Immunohistochemical assessment of E-cadherin and beta-catenin in the histological
      differentiations of oral squamous cell carcinoma.
AB  - The aim of this study was to establish the expression and localization of E
      cadherin and beta-catenin in oral squamous cell carcinomas (OSCC) so that we
      could correlate the findings with prognostic-relevant histopathological
      variables. E-cadherin and beta-catenin expression in normal oral epithelia and in
      oral squamous cell carcinomas was examined immunohistochemically, and
      associations with histopathological differentiation and prognosis were then
      analyzed in 33 patients who had been operated on for OSCC. E-cadherin expression
      was found in (82%) of the squamous cells of well differentiated OSCC, (61%) of
      moderately differentiated and (39%) of poorly differentiated. E-cadherin
      expression was significantly associated with histological grade (p=0.000). No
      nuclear staining was detected. In (19.5%) of the cells E-cadherin localized in
      the cytoplasm, with no correlation to the histological grade (p=0.106). beta
      Catenin expression was found in 87% of the squamous cells of well differentiated
      OSCC, 67% of moderately differentiated and 43% of poorly differentiated, the
      expression was significantly associated with histological grade (p=0.000). the
      nuclear beta-Catenin expression appeared in 3.3% of the cells and it was
      correlated to the histological grade (p=0.000). In (23.5%) of the cells beta
      Catenin localized in the cytoplasm, with correlation to the histological grade
      (p=0.002). According to this study the expression of beta-catenin and E-cadherin
      were independent prognostic factors for histological grade. E-cadherin was
      closely linked to beta-catenin expression in OSCC (p=0.000) and to tumor
      differentiation. That reflects a structural association and the role of both in
      tumor progression. 

PMID- 25374219
TI  - Impact of chemotherapy-related hyperglycemia on prognosis of child acute
      lymphocytic leukemia.
AB  - PURPOSE: To investigate the impact of hyperglycemia during inductive treatment on
      the prognosis of acute lymphocytic leukemia (ALL) in children. MATERIALS AND
      METHODS: Clinical data of 159 ALL childhood cases were reviewed. The patients
      were divided into the hyperglycemia group (fasting glucose>=126 mg/dl and/or
      random blood glucose>=200 mg/dl) and the euglycemia group according to the blood
      glucose values. The ?2 test was performed to compare the complete remission rates
      of the two groups, and Kaplan-Meier and log-rank tests were performed to compare
      the 5-year overall and relapse-free survival. RESULTS: The incidence of
      hyperglycemia in the age>=10-year-old group was higher than the younger-age group
      (P=0.009). Values in the interim- and high-risk groups were higher than the
      standard-risk group (P=0.028), while there was no significant difference between
      genders (P=0.056). The complete remission rates of the 2 groups demonstrated no
      significant difference (P=0.134), while the 5-year OS of the hyperglycemia group
      was lower than in the euglycemia group (83.8+/-6.0% vs 94.9+/-2.4%, P=0.014). The
      5 -year RFS was significantly lower than the euglycemia group (62.9+/-8.7%) vs
      80.2+/-9.1%, P<0.001). CONCLUSIONS: Children with age>=10 years old, and in the
      middle- and high-risk groups appear prone to complicating hyperglycemia during
      inductive chemotherapy, associated with lower 5-year OS and RFS.

PMID- 25374220
TI  - High expression of Bcl-2 protein predicts favorable outcome in non-small cell
      lung cancer: evidence from a systematic review and meta-analysis.
AB  - BACKGROUND: The prognostic value of Bcl-2 protein expression in non-small cell
      lung cancer (NSCLC) is under debate. We therefore systematically reviewed the
      evidence for Bcl-2 protein effects on NSCLC survival to elucidate this issue.
      MATERIALS AND METHODS: An electronic search in Pubmed and Embase complemented by
      manual searches in article references were conducted to identify eligible studies
      to evaluate the association between Bcl-2 protein expression and overall survival
      (OS) as well as disease free survival (DFS) of NSCLC patients. Combined hazard
      ratios (HRs) with corresponding 95% confidence intervals (95%CIs) were pooled
      using the random-effects model. RESULTS: A total of 50 trials (including 52
      cohorts) encompassing 7,765 patients were pooled in the meta-analysis regarding
      Bcl-2 expression and OS of NSCLC patients. High expression of Bcl-2 protein had a
      favorable impact (HR=0.76, 95%CI=0.67-0.86). In the group of Bcl-2 expression and
      DFS, 11 studies including 2,634 patients were included. The synthesized result
      indicated high expression of Bcl-2 protein might predict good DFS (HR=0.85,
      95%CI=0.75-0.95). CONCLUSIONS: Our present meta-analysis demonstrated favorable
      prognostic values of Bcl-2 expression in patients with NSCLC. Further prospective
      trails are welcomed to validate the utility of assessing Bcl-2 in NSCLC patient
      management.

PMID- 25374221
TI  - Adjuvant radiotherapy for gastric carcinoma: 10 years follow-up of 244 cases from
      a single institution.
AB  - BACKGROUND: Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves
      survival among high- risk patients. This study was undertaken to analyse long
      term survival probability and the impact of certain covariates on the survival
      outcome in affected individuals. MATERIALS AND METHODS: Between January 2000 and
      December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy
      (RT) in our institution. Data were retrieved retrospectively from patient files
      and analysed with SPSS version 21.0. RESULTS: A total of 244 cases, with a male
      to female ratio of 2.2:1, were enrolled in the study. The median age of the
      patients was 52 years (range, 20-78 years). Surgical margin status was positive
      or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46
      Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2
      155 months) for surviving patients and all patients, respectively. Actuarial
      overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24%
      and 16%, respectively. Actuarial progression free survival (PFS) probability was
      69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease,
      subtotal gastrectomy and adjuvant CRT were significantly associated with improved
      OS and PFS in multivariate analyses. Surgical margin status or lymph node
      dissection type were not prognostic for survival. CONCLUSIONS: Postoperative CRT
      should be considered for all patients with high risk of recurrence after
      gastrectomy. Beside well-known prognostic factors such as stage, lymph node
      status and concurrent chemotherapy, the type of gastrectomy was an important
      prognostic factor in our series. With our findings we add to the discussion on
      the definition of required surgical margin for subtotal gastrectomy. We consider
      that our observations in gastric cancer patients in our clinic can be useful in
      the future randomised trials to point the way to improved outcomes.

PMID- 25374222
TI  - Objective and subjective socioeconomic position and current smoking among Korean
      adolescents.
AB  - BACKGROUND: Despite social gradients in adult smoking, the effects of
      socioeconomic position (SEP) on adolescent smoking is not well understood. This
      study examined effects of subjective SEP as well as the objective SEP on smoking
      among Korean adolescents. MATERIALS AND METHODS: Data were obtained from the 2012
      Korea Youth Risk Behavior Web-based Survey, a nationally representative sample of
      middle and high school students (38,221 boys; 35,965 girls). SEP was assessed by
      the Family Affluence Scale (FAS) and the self-rated household economic status.
      Relationships between SEP and smoking were analyzed by multivariate logistic
      regression. RESULTS: The low perceived SEP for either the high or low FAS grade
      was related to an elevated likelihood of smoking in both genders. A significantly
      higher risk of smoking was found in boys of low perceived SEP in middle school
      (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.28-1.77 for high FAS, OR
      1.55; 95% CI 1.21-1.98 for low FAS), and of low perceived SEP and high FAS in
      high school (OR 1.13; 95% CI 1.02-1.26). Among girls, an elevated risk of smoking
      was observed in middle school group with low perceived SEP and low FAS (OR 2.01;
      95% CI 1.44-2.79) and in the high school group of low perceived SEP, regardless
      of FAS level (OR 1.34; 95% CI 1.14-1.57 for high FAS, OR 1.31; 95% CI 1.04-1.65
      for low FAS). CONCLUSIONS: The relationship of subjectively perceived SEP with
      smoking is as important as objective SEP and more significant in Korean high
      school adolescents.

PMID- 25374223
TI  - Real-time PCR detection of 16S rRNA novel mutations associated with Helicobacter
      pylori tetracycline resistance in Iran.
AB  - BACKGROUND: Tetracycline is an antibiotic widely used for the treatment of
      Helicobacter pylori infection, but its effectiveness is decreasing due to
      increasing bacterial resistance. The aim of this study was to investigate the
      occurrence of 16S rRNA mutations associated with resistance or reduced
      susceptibility to tetracycline of Helicobacter pylori by real-time PCR (RT-PCR)
      assays from culture. MATERIALS AND METHODS: Tetracycline susceptibility and
      minimal inhibition concentration (MIC) was determined by the Epsilometer test
      (Etest) method. A LightCycler assay developed to detect these mutations was
      applied to DNA extracted from culture. The 16S rRNA of these isolates was
      sequenced and resistance-associated mutations were identified. From 104 isolates
      of H. pylori examined, 11 showed resistance to tetracycline. RESULTS: LightCycler
      assay was applied to DNA extracted from 11 tetracycline-susceptible and 11
      tetracycline resistance H. pylori isolates. In our study the sequencing of the H.
      pylori wild types in 16 s rRNA gene were AGA 926-928 with MIC (0.016 to 0.5
      MUg/ml), while the sequencing and MIC for resistant were GGA and AGC, (0.75 to
      1.5 MUg/ml), respectively. Also we found a novel mutation in 2 strains with 84
      degrees  as their melting temperatures and exhibition of an A939C mutation.
      CONCLUSIONS: We conclude that real-time PCR is an excellent method for
      determination of H. pylori tetracycline resistance related mutations that could
      be used directly on biopsy specimens.

PMID- 25374224
TI  - Survival analysis of oral squamous cell carcinoma in a subgroup of young
      patients.
AB  - Oral squamous cell carcinoma (OSCC) is predominantly a disease of middle-aged men
      with long-term exposure to tobacco and alcohol. An increasing trend has been
      reported at a younger age worldwide. Clinical records of 100 patients under the
      age of 45 years treated specifically for oral cavity SCC in our hospital during a
      10-year period were retrospectively analyzed to calculate the survival rates. An
      obvious male predominance coincided with smoking trend among Chinese young
      individuals and female patients were more likely to have no traditional risk
      factors such as smoking or drinking. The 5-year overall survival rate and disease
      free survival rate were 61.0% and 75.5%, respectively, consistent with other
      published series over the decade showing a relatively better survival among the
      young. No significant differences clearly correlated with outcome when comparing
      non-smokers non-drinkers to ever-smokers and ever drinkers (P>0.05). Overall
      survival rate and disease free survival rate was found to be significantly higher
      in patients with early-stage disease than with advanced stage disease (P=0.001,
      P=0.009 respectively). The strong influence of clinical stage on prognosis
      emphasizes the importance of early diagnosis and treatment of oral malignancies
      for this unique clinical subgroup. 

PMID- 25374225
TI  - Association of miR-193b down-regulation and miR-196a up-regulation with
      clinicopathological features and prognosis in gastric cancer.
AB  - Dysregulated expression of microRNAs (miRNAs) has been shown to be closely
      associated with tumor development, progression, and carcinogenesis. However,
      their clinical implications for gastric cancer remain elusive. To investigate the
      hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer
      tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were
      employed to examine miRNA expression profiles for the 5-pair discovery stage, and
      the quantitative real-time polymerase chain reaction (qRT- PCR) was applied to
      validate candidate miRNAs for 48-pair validation stage. Furthermore, the
      relationship between altered miRNA and clinicopathological features and prognosis
      of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs
      were found to be significantly different expressed in tissues from gastric cancer
      compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression
      of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was
      significantly correlated with Lauren type, differentiation, UICC stage, invasion,
      and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was
      significantly associated with poor differentiation (p=0.022). Moreover, binary
      logistic regression analysis demonstrated that the UICC stage was a significant
      risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91;
      p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with
      a high fold-change of down-regulated miR-193b had a significantly shorter
      survival time (n=19; median survival=29 months) compared to patients with a low
      fold-change of down-regulated miR-193b (n=29; median survival=54 months)
      (p=0.001). Overall survival time of patients with a low fold-change of up
      regulated miR- 196a (n=27; median survival=52 months) was significantly longer
      than that of patients with a high fold-change of up-regulated miR-196a (n=21;
      median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied
      as novel and promising prognostic markers in gastric cancer. 

PMID- 25374226
TI  - Genetic variation in PSCA is associated with bladder cancer susceptibility in a
      Korean population.
AB  - BACKGROUND: Genetic factors play important roles in the pathogenesis of human
      cancer. A recent genome wide association study (GWAS) identified an association
      between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene
      and bladder cancer risk in Caucasians. The aim of this study was to determine
      whether the rs2294008 polymorphism is similarly associated with bladder cancer
      susceptibility in a Korean population. MATERIALS AND METHODS: We conducted a case
      control study of 411 bladder cancer patients and 1,700 controls. RESULTS: The
      frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were
      16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in
      controls, respectively. We found that the combined CT/TT genotypes were
      associated with a significantly increased risk of bladder cancer (OR CT/TT=1.58,
      95% CI=1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and
      tumor stage did not modify the association between rs2294008 and the risk of
      bladder cancer. CONCLUSIONS: Our study showed that the rs2294008 polymorphism in
      the PSCA gene is associated with the risk of bladder cancer in a Korean
      population, providing evidence that it may contribute to bladder carcinogenesis
      regardless of ethnicity.

PMID- 25374227
TI  - Association of knowledge, attitude and demographic variables with cervical Pap
      smear practice in Nepal.
AB  - BACKGROUND: Coverage of cervical pap smear test in Nepal is below general global
      values. One of the reasons may be that cervical cancer prevention policy of Nepal
      has 'Visual Inspection of Cervix with Acetic Acid' as the only screening tool.
      The focus of present study was to find out association of demographic factors,
      knowledge and attitude regarding cervical Pap smear test with its practice by
      women in Nepal. MATERIALS AND METHODS: This cross sectional analytical
      observational study was conducted between February 1, 2013 and April 30, 2013.
      Participants were interviewed with the help of a structured questionnaire. Chi
      square and multivariate logistic regression tests were used to detect
      associations of variables with pap smear practice. RESULTS: Chi square test
      showed that practice was significantly associated with knowledge about pap smear
      test and cervical cancer, having favourable attitude towards the test, urban
      residency and 36-50 years age-group. Pap smear utilization was not associated
      with age-at-marriage, parity and age-at-first-child-birth. Multivariate logistic
      regression showed favorable attitude towards pap smear test as the only variable
      which significantly influenced pap smear practice (p=0.006, OR: 2.4).
      CONCLUSIONS: Pap smear coverage has been found to be 15.7% which is lower than
      global average and that for developing countries. Health education programs which
      are effective not only in increasing knowledge about cervical cancer and pap
      smear test but also effective in positively changing attitude towards the test
      should be organized to increase pap smear coverage.

PMID- 25374229
TI  - Effect of route of preoperative biopsy on endoscopic submucosal dissection for
      patients with early gastric cancer.
AB  - OBJECTIVE: To observe and compare the effects of multi-patch biopsy under
      conventional white light imaging endoscopy (C-WLI) and precise targeted biopsy
      under magnifying narrow-band imaging endoscopy (M-NBI) on the endoscopic
      submucosal dissection (ESD) of early gastric cancers and intraepithelial
      neoplasias. METHODS: According to the way of selecting biopsy specimens, patients
      were divided into C-WLI and M-NBI groups, 20 cases. The ESD operations of the 2
      groups were compared quantitively. RESULTS: The mean frequency of biopsy in M-NBI
      group was (1.00+/-0.00), obviously lower than in the C-WLI group (4.78+/-1.02)
      (P<0.01).The average total number of selected biopsy specimens was also fewer
      (1.45+/-0.12 and 7.82+/-2.22, respectively, P<0.01). There was no significant
      difference in the time of determining excision extension, marking time and the
      time of specimen excision of 2 groups during the ESD (P>0.05), whereas submucosal
      injection time, mucosal dissection time, stopping bleeding time, wound processing
      time in the M-NBI group were significantly shorter than in the C-WLI group
      (P<0.01). CONCLUSION: Precise targeted biopsy under M-NBI can obviously shorten
      the time of ESD operation, with small quantity of tissues but high pathological
      positive rate.

PMID- 25374228
TI  - Prognostic value of SPARC expression in unresectable NSCLC treated with
      concurrent chemoradiotherapy.
AB  - BACKGROUND: The aim of the present study was to determine the
      predictive/prognostic value of the secreted protein, acidic and rich in cysteine
      (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer.
      MATERIALS AND METHODS: The study included 84 patients with Stage IIIA-B non-small
      cell lung cancer, undergoing simultaneous chemoradiotherapy including
      radiotherapy at a dose of 66 Gy and weekly docataxel (20 mg/m2) and cisplatin (20
      mg/m2). SPARC expression was studied in biopsy material by immunohistochemical
      methods and correlations with treatment responses or survival were evaluated.
      RESULTS: Median overall survival was 16+/-2.73 (11.55-20.46) months for low
      expression vs 7+/-1.79 months (7.92-16.08) months for high expression (p=0.039),
      while median local control was 13+/-2.31 (8.48-17.5) months for low expression vs
      6+/-0.85 (4.34-7.66) months for high expression (p=0.045) and median progression
      free survival was 10+/-2.31 (5.48-14.5) months for low expression vs 6+/-1.10
      (3.85-8.15) months for high expression (p=0.022). In both univariate and
      multivariate analyses, high SPARC expression was associated with significantly
      shorter overall survival (p=0.003, p=0.007, respectively), local control
      (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared
      to low SPARC expression. No significant difference was detected between high and
      low SPARC expression groups regarding age, sex, T stage, N stage, histopathology
      and stage-related patient characteristics. CONCLUSIONS: High SPARC expression was
      identified as a poor prognostic factor in cases with locally advanced NSCLC
      treated with concurrent chemoradiotherapy.

PMID- 25374230
TI  - High monocarboxylate transporter 4 protein expression in stromal cells predicts
      adverse survival in gastric cancer.
AB  - BACKGROUND: Increasing evidence suggests that stromal monocarboxylate transporter
      4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor
      development. However, their clinical value remains largely unexplored in gastric
      cancer (GC). The present study aimed to determine clinicopathological
      significance and prognostic values of stromal MCT4 and CA IX in GC. MATERIALS AND
      METHODS: Specimens from 143 GC patients were immunohistochemically stained using
      polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with
      patient clinicopathologic characteristics and survival data. RESULTS: High
      stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in
      74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM
      stage (p=0.000; p=0.000). High CA IX expression was positively related to depth
      of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival
      analysis indicated high expression of stromal MCT4 to be an independent factor in
      predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040)
      and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC
      patients. However, high CA IX expression exhibited no significant predictive
      value. CONCLUSIONS: These findings suggest that high expression of stromal MCT4
      and CA IX proteins is significantly correlated with GC progression. High stromal
      MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic
      marker and therapeutic target.

PMID- 25374231
TI  - Comparison between effects of free curcumin and curcumin loaded NIPAAm-MAA
      nanoparticles on telomerase and PinX1 gene expression in lung cancer cells.
AB  - BACKGROUND: Herbal compounds such as curcumin which decrease telomerase and gene
      expression have been considered as beneficial tools for lung cancer treatment. In
      this article, we compared the effects of pure curcumin and curcumin-loaded NIPAAm
      MAA nanoparticles on telomerase and PinX1 gene expression in a lung cancer cell
      line. MATERIALS AND METHODS: A tetrazolium-based assay was used for determination
      of cytotoxic effects of curcumin on the Calu-6 lung cancer cell line and
      telomerase and pinX1 gene expression was measured with real-time PCR. RESULTS:
      MTT assay showed that Curcumin-loaded NIPAAm-MAA inhibited the growth of the Calu
      6 lung cancer cell line in a time and dose-dependent manner. Our q-PCR results
      showed that the expression of telomerase gene was effectively reduced as the
      concentration of curcumin-loaded NIPAAm-MAA increased while expression of the
      PinX1 gene became elevated. CONCLUSIONS: The results showed that curcumin- loaded
      NIPAAm-MAA exerted cytotoxic effects on the Calu-6 cell line through down
      regulation of telomerase and stimulation of pinX1 gene expression. NIPPAm-MAA
      could be good carrier for such kinds of hydrophobic agent.

PMID- 25374232
TI  - Prostate biopsy in the elderly: histologic findings and treatment necessity.
AB  - The aim of this study is to determine results of high prostate specific antigen
      (PSA) or abnormal digital rectal examination driven prostate biopsies performed
      in our Department in men aged 75 or more and to show the characteristics of
      pathology results. The hospital records of the patients who had high PSA or
      abnormal digital rectal examination driven prostate biopsy in two common
      university based research hospitals have been reviewed retrospectively. Patients
      aged 75 years or older at the date of biopsy whose records provided pathology
      results and full medical history were evaluated for the study. A total of 103
      patients were evaluated with a mean age of 79.4+/-3.4 years. More than half of
      the patients (55.1%) were in their seventh decade and the rest were in the eighth
      decade. Median PSA value was 15.0 (range 2.1-4500) ng/ml. In most of the biopsies
      (67%), PSA levels were lower than 20 ng/ml. In almost half of the patients (48%),
      digital rectal examination was abnormal. In 68.9% of the patients, there were at
      least one or more associated co-morbid diseases. Gleason scores were 7 or higher
      in 73%, and 8 or higher in 37% of the patients with prostate cancer. Four of the
      70 (6%) patients had bone metastases. Castrations were applied to most of the
      patients with prostate adenocarcinoma (%79). High percentage of high grade
      (Gleason 7 or more) prostate adenocarcinoma in the elderly refutes the perception
      of prostate cancer in this age group as clinically insignificant. Therefore, it
      is to be kept in mind that prostate cancer in the elderly an be clinically
      significant and prostate biopsies are to be performed when necessary.

PMID- 25374233
TI  - Breast cancer awareness among Turkish nursing students.
AB  - BACKGROUND: This study conducted to determine breast cancer awareness and
      influencing factors among nursing students in the West Black Sea Region in
      Turkey. MATERIALS AND METHODS: This cross-sectional descriptive study was
      conducted between April-May, 2014. The sample was 270 female nursing students.
      Data were collected by Personal Information Form and Champion's Health Belief
      Model Scale (CHBMS). RESULTS: The students' mean age was 21.6+/-2.09 and 81.1%
      had knowledge about breast cancer from their academic education. It is found that
      63.7% of the students performed Breast Self-Examination (BSE) and 11.1% had a
      family member diagnosed with breast cancer. The CHBMS mean score of the students
      was 117.7+/-14.5. CONCLUSIONS: Breast cancer awareness of nursing students is on
      a good level and was affected by family history of breast cancer and health
      beliefs.

PMID- 25374234
TI  - Heat-shock protein 70 as a tumor antigen for in vitro dendritic cell pulsing in
      renal cell carcinoma cases.
AB  - Immunological functions of heat shock proteins (HSPs) have long been recognized.
      In this study we aimed to efficiently purify HSP70 from renal cell carcinoma and
      test it as a tumor antigen for pulsing dendritic cells in vitro. HSP70 was
      purified from renal cell carcinoma specimens by serial column chromatography on
      Con A-sepharose, PD-10, ADP-agarose and DEAE-cellulose, and finally subjected to
      fast protein liquid chromatography (FPLC). Dendritic cells derived from the
      adherent fraction of peripheral blood mononuclear cells were cultured in the
      presence of IL-4 and GM-CSF and exposed to tumor HSP70. After 24 hours, dendritic
      cells were phenotypically characterized by flow cytometry. T cells obtained from
      the non-adherent fraction of peripheral blood mononuclear cells were then co
      cultured with HSP70-pulsed dendritic cells and after 3 days T cell cytotoxicity
      towards primary cultured renal cell carcinoma cells was examined by Cell Counting
      Kit-8 assay. Dendritic cells pulsed in vitro with tumor-derived HSP70 expressed
      higher levels of CD83, CD80, CD86 and HLA-DR maturation markers than those pulsed
      with tumor cell lysate and comparable to that of dendritic cells pulsed with
      tumor cell lysate plus TNF-alpha. Concomitantly, cytotoxic T-lymphocytes induced
      by HSP70-pulsed dendritic cells presented the highest cytotoxic activity. There
      were no significant differences when using homologous or autologous HSP70 as the
      tumor antigen. HSP70 can be efficiently purified by chromatography and induces in
      vitro dendritic cell maturation in the absence of TNF-alpha. Conspecific HSP70
      may effectively be used as a tumor antigen to pulse dendritic cells in vitro. 

PMID- 25374235
TI  - Distribution characteristics of 3,369 chinese colorectal cancer patients for
      gender, age, location and tumor size during colonoscopy.
AB  - BACKGROUND: Studies have shown the existence of gender- and age-related
      differences in the incidence and anatomic distribution of colorectal cancers. The
      purposes of this study were to analyze the distribution characteristics of
      colorectal cancer patients regarding gender, age, location and tumor size in the
      course of colonoscopy. MATERIALS AND METHODS: All colorectal cancer patients who
      underwent colonoscopy in the First Affiliated Hospital of Guangxi Medical
      University from 2003 to 2012 were included in our retrospective study.
      Demographic information (age and gender) and colonoscopy report information
      (tumor size and location) were collected and analyzed. To compare the gender
      differences in tumor location and tumor size, as well as the size differences in
      tumor location, the chi-square test was used. RESULTS: A total of 3, 369
      colorectal cancer patients (2, 007 men vs 1, 362 women) were included in our
      study. Statistical analysis showed there was no gender difference in the anatomic
      distribution of the tumors (p>0.05). However, there was a gender difference in
      tumor size (p>0.05). In addition, our study found there was a significant
      difference in tumor size between rectal and colon tumors (p>0.001). CONCLUSIONS:
      There was no gender difference in the anatomic distribution of colorectal tumors.
      In addition, tumors observed in men were larger than in women.

PMID- 25374236
TI  - Screening of differential promoter hypermethylated genes in primary oral squamous
      cell carcinoma.
AB  - BACKGROUND: Promoter hypermethylation leads to altered gene functions and may
      result in malignant cellular transformation. Thus, identification of biomarkers
      for hypermethylated genes could be useful for diagnosis, prognosis, and
      therapeutic treatment of oral squamous cell carcinoma (OSCC). OBJECTIVES: To
      screen hypermethylated genes with a microarray approach and to validate selected
      hypermethylated genes with the methylation-specific polymerase chain reaction
      (MSPCR). MATERIALS AND METHODS: Genome-wide analysis of normal oral mucosa and
      OSCC tissues was conducted using the Illumina methylation microarray. The
      specified differential genes were selected and hypermethylation status was
      further verified with an independent cohort sample of OSCC samples. Candidate
      genes were screened using microarray assay and run by MSPCR analysis. RESULTS:
      TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential
      hypermethylation status. CONCLUSIONS: Our microarray screening and MSPCR
      approaches revealed that the signature candidates of differentially
      hypermethylated genes may possibly become potential biomarkers which would be
      useful for diagnostic, prognostic and therapeutic targets of OSCC in the near
      future.

PMID- 25374237
TI  - Association between survivin gene polymorphisms and the susceptibility to colon
      cancer development in the Turkish population.
AB  - BACKGROUND: Colon cancer is one of the most common cancers worldwide. Apoptosis
      is a necessary physiological process for cell elimination which is very important
      both cellular homeostasis and cell proliferation and differantiation.
      Dysregulation can lead to uncontrolled cell growth and tumor development.
      Survivin, a member of the IAP family, plays a key role in promotion of cell
      proliferation as well as inhibition of apoptosis in cancer cells. The aim of this
      study was to investigate whether specific genetic polymorphisms of survivin could
      be associated with colon cancer development and progression in a Turkish
      population. Our study is the first to our knowledge to investigate the
      relationship between colon cancer risk and survivin gene polymorphisms. MATERIALS
      AND METHODS: The relation between colon cancer and survivin -31 G/C (rs9904341), 
      241 C/T (rs17878467) and -625 C/G (rs8073069) polymorphism in promotor site of
      survivin gene associated with apoptosis was investigated using the polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
      RESULTS: Individuals with -31C allele and CC genotype were found to have a higher
      risk of developing colon cancer (OR=13.4, p=0.01). The -241 CT genotype
      considerably increased the risk of colon cancer (OR=12.0, p=0.0001). However,
      there was no significant varaition of the survivin -625 C/G polymorphism among
      colon cancer patients and controls in our study. CONCLUSIONS: This study provides
      the first evidence that survivin -31 G/C and -241 C/T SNP significantly
      contribute to the risk of colon cancer in the Turkish population.

PMID- 25374238
TI  - Health promoting lifestyle behaviour in medical students: a multicentre study
      from Turkey.
AB  - BACKGROUND: The aim of this study was to determine the predictors of health
      promoting lifestyle behaviour among medical students attending seven of the
      medical schools in Turkey. MATERIALS AND METHODS: This cross- sectional
      descriptive study was performed during the second semester of the first and last
      (sixth) years of study from March to May 2011. A questionnaire with two sections
      was specifically designed. The first section contained questions on demographic
      characteristics; the second consisted of the Health Promoting Lifestyle Profile
      II (HPLP) Scale. From a total of 2,309 medical students, 2,118 (response rate
      91.7%) completed the questionnaire. Data were analyzed using descriptive
      statistics, t, Anova, Tukey test and binary logistic regression analysis. The
      research was approved by the Ethics Committee of Erciyes University. RESULTS: The
      mean age was 20.7+/-2.9 years and it was found that 55.1% were men, 62.3% were in
      the first year. The overall prevalence of smoking was 19.1%, and for drinking
      alcohol was 19.4%. HPLP point averages of the first year students were 129.2+/
      17.7, and for last year 125.5+/-19.0. The overall mean score for the HPLP II was
      2.5+/-0.4. They scored highest on the spiritual growth subscale (2.9+/-0.5),
      interpersonal relations (2.8+/-0.5), health responsibility subscale (2.3+/-0.5),
      nutrition subscale (2.3+/-0.5), stress management subscale (2.3+/-0.4), and the
      lowest subscale physical activity (2.0+/-0.5). It is established that student's
      grade, educational level of parents, economic status of family, marital status,
      smoking and general health perception of the students resulted in a significant
      difference in HPLP Scale total score average and the mean score of majority of
      subscales.There was no statistically significant difference between the total
      HPLP when evaluated for gender, chronic disease, alcohol drinking status and BMI.
      CONCLUSIONS: Based on these results, particularly in the curriculum of medical
      students in order to increase positive health behaviours including physical
      activity, health promotion issues, and giving more space to aim at behaviour
      change in these matters is recommended.

PMID- 25374239
TI  - Functional investigation on aromatase in endometrial hyperplasia in polycystic
      ovary syndrome cases.
AB  - OBJECTIVE: To explore the possible significance of aromatase P450 in endometrial
      hyperplasia with a background of polycystic ovary syndrome (PCOS). METHODS:
      Immunohistochemistry was used to determine the expression of aromatase P450 in
      endometrium of PCOS patients. Semiquantitative analysis of aromatase P450
      expression of mRNA and protein level wasalso carried out by real-time
      quantitative RT-PCR method. After endometrial cells were stimulated by
      testosterone and letrozole in vitro, the estradiol (E2) level was determined, and
      the expression of cell aromatase P450 mRNA was assessed. RESULTS: The aromatase
      P450 mRNA level was increased in endometria of PCOS patients. When endometrial
      cells were cultured with 10-6 M testosterone, the E2 level in the culture medium
      increased. An inhibitory effect on E2 generation and expression of aromatase P450
      mRNA was observed when the endometrial cells were treated with 10(-5) M
      letrozole. CONCLUSIONS: There is an increased expression of aromatase P450 in
      PCOS patient endometrium. Androgen stimulation could enhance the synthesis of
      aromatase P450 mRNA and the production of E2 in endometrial cells in vitro while
      letrozole could do the reverse.

PMID- 25374240
TI  - Preparation of lysine-coated magnetic Fe2O3 nanoparticles and influence on
      viability of A549 lung cancer cells.
AB  - OBJECTIVE: To explore the effect of lysine-coated oxide magnetic nanoparticles
      (Lys@MNPs) on viability and apoptosis of A549 lung cancer cells. METHODS:
      Transmission electron microscopy (TEM), vibrating sample magnetometer (VSM) and
      Zeta potentiometric analyzer were employed to characterize Lys@MNPs. Then
      Lys@MNPs and lung cancer A549 cells were co-cultured to study the effect of
      Lys@MNPs on cell viability and apoptosis. The pathway of Lys@MNPs entering A549
      cells was detected by TEM and cell imaging by 1.5 T MRI. RESULTS: Lys@MNPs were
      10.2 nm in grain diameter, characterized by small size, positive charge, and
      superparamagnetism. Under low-dose concentration of Lys@MNPs (<40 MUg/mL), the
      survival rate of A549 cells was decreased but remained higher than 95% while
      under high-dose concentration (100 MUg/mL), the survival ratewas still higher
      than 80%, which suggested Lys@MNPs had limited influence on the viability of A549
      cells, with good biocompatibility and and no induction of apoptosis. Moreover,
      high affinity for cytomembranes, was demonstrated presenting good imaging
      effects. CONCLUSION: Lys@MNPs can be regarded as a good MRI negative contrast
      agents, with promising prospects in biomedicine.

PMID- 25374241
TI  - Definitive concurrent chemoradiotherapy in cervical cancer--a University of
      Malaya Medical Centre experience.
AB  - BACKGROUND: The efficacy of concurrent chemoradiotherapy in the treatment of
      locally advanced cervical cancer is well established. We aimed to investigate the
      long-term efficacy of definitive concurrent chemoradiotherapy for cervical cancer
      in the University of Malaya Medical Centre. MATERIALS AND METHODS: A cohort of 60
      patients with FIGO stage IB2-IVA cervical cancer who were treated with definitive
      concurrent chemoradiotherapy with cisplatin followed by intracavitary
      brachytherapy or external beam radiotherapy (EBRT) boost between November 2001
      and May 2008 were analysed. Patients were initially treated with weekly
      intravenous cisplatin (40 mg/m2) concurrent with daily EBRT to pelvis of 45-50 Gy
      followed by low dose rate brachytherapy or EBRT boost to tumour. Local control
      rate, progression free survival, overall survival and treatment related
      toxicities graded by the RTOG criteria were evaluated. RESULTS: The mean age was
      56. At the median follow-up of 72 months, the estimated 5-year progression-free
      survival (PFS) (median PFS 39 months) and the 5-year overall survival (OS)
      (median OS 51 months) were 48% and 50% respectively. The 5-year local control
      rate was 67.3%. Grade 3-4 late gastrointestinal and genitourinary toxicity
      occurred in 9.3% of patients. CONCLUSIONS: The 5-year PFS and the 5-year OS in
      this cohort were lower than in other institutions. More advanced stage at
      presentation, longer overall treatment time (OTT) of more than fifty-six days and
      lower total dose to point A were the potential factors contributing to a lower
      survival.

PMID- 25374242
TI  - Economic evaluation and budget impact analysis of the surveillance program for
      hepatocellular carcinoma in Thai chronic hepatitis B patients.
AB  - BACKGROUND: The incidence rate and the treatment costs of hepatocellular
      carcinoma (HCC) are high, especially in Thailand. Previous studies indicated that
      early detection by a surveillance program could help by down-staging. This study
      aimed to compare the costs and health outcomes associated with the introduction
      of a HCC surveillance program with no program and to estimate the budget impact
      if the HCC surveillance program were implemented. MATERIALS AND METHODS: A cost
      utility analysis using a decision tree and Markov models was used to compare
      costs and outcomes during the lifetime period based on a societal perspective
      between alternative HCC surveillance strategies with no program. Costs included
      direct medical, direct non-medical, and indirect costs. Health outcomes were
      measured as life years (LYs), and quality adjusted life years (QALYs). The
      results were presented in terms of the incremental cost-effectiveness ratio
      (ICER) in Thai THB per QALY gained. One- way and probabilistic sensitivity
      analyses were applied to investigate parameter uncertainties. Budget impact
      analysis (BIA) was performed based on the governmental perspective. RESULTS: Semi
      annual ultrasonography (US) and semi-annual ultrasonography plus alpha
      fetoprotein (US plus AFP) as the first screening for HCC surveillance would be
      cost-effective options at the willingness to pay (WTP) threshold of 160,000 THB
      per QALY gained compared with no surveillance program (ICER=118,796 and
      ICER=123,451 THB/QALY), respectively. The semi-annual US plus AFP yielded more
      net monetary benefit, but caused a substantially higher budget (237 to 502
      million THB) than semi-annual US (81 to 201 million THB) during the next ten
      fiscal years. CONCLUSIONS: Our results suggested that a semi-annual US program
      should be used as the first screening for HCC surveillance and included in the
      benefit package of Thai health insurance schemes for both chronic hepatitis B
      males and females aged between 40-50 years. In addition, policy makers considered
      the program could be feasible, but additional evidence is needed to support the
      whole prevention system before the implementation of a strategic plan.

PMID- 25374243
TI  - Clinical characteristics and Helicobacter pylori status of gastric cancer in
      Thailand.
AB  - BACKGROUND: Gastric cancer is the second leading course of cancer death worldwide
      and H. pylori infection is an important risk factor for gastric cancer
      development. This study was design to evaluate the clinical, pathological
      features, survival rate and prevalence of H. pylori infection in gastric cancer
      in Thailand. MATERIALS AND METHODS: Clinical information, histological features,
      endoscopic findings and H. pylori status were collected from gastric cancer
      patients from Thammasat university hospital during June 1996-December 2011. H.
      pylori infection was assessed by histological evaluation, rapid urease test and
      serological test. Clinical information, endoscopic findings and histopathology of
      all patients were recorded and compared between patients with active or non
      active H. pylori infection. RESULTS: A total of 100 gastric cancer patients (55
      men and 45 women with mean age of 55+/-16.8 years) were enrolled in this study.
      Common presenting symptoms were dyspepsia (74%), weight loss (66%), anemia (63%)
      and anorexia (38%). Mean duration of symptoms prior to diagnosis was 98 days.
      Overall prevalence of H. pylori infection was 83% and active H. pylori infection
      was 40%. 1-year and 5-year survival rates were 43% and 0%. There was no
      significant difference between active H. pylori infection in different locations
      (proximal vs non-proximal: 47.1% vs 48.5%; P-value=0.9, OR=0.9; 95%CI=0.3-3.1)
      and histology of gastric cancer (diffuse type vs intestinal type: 47.4% vs 50%; P
      value=0.8, OR=0.9, 95%CI=0.3-2.7). However, linitis plastica was significantly
      more common in non-active than active H. pylori infection (27.9% vs 0%; P
      value<0.0001, OR=13.3, 95%CI=3.2-64.5). Moreover, gastric cancer stage 4 was
      higher in non-active than active H. pylori infection (93% vs 50%, P-value<0.001).
      CONCLUSIONS: Prevalence of H. pylori infection in Thai gastric cancer patients
      was high but active infection was low. Most gastric cancer patients presented in
      advance stage and had a grave prognosis. Screening for gastric cancer in high
      risk individuals might be an appropriate tool for early detection and improve the
      treatment outcome for this particular disease in Thailand.

PMID- 25374244
TI  - Efficacy of permanent iodine-125 seed implants and gemcitabine chemotherapy in
      patients with platinum- resistant recurrent ovarian carcinoma.
AB  - BACKGROUND: The aim of this study was to explore the efficacy and adverse
      reactions of CT-guided radioactive 125I-seed implantation treatment combined with
      chemotherapy for platinum-resistant recurrent ovarian carcinoma. MATERIALS AND
      METHODS: From September 2010 to December 2012, 23 patients with platinum
      resistant recurrent ovarian carcinoma were enrolled. All the patients refused,
      could not bear, or were not suitable for surgery. They all had no more than 3
      lesions, which were detected and could also be measured by CT. All were clarified
      as single-lesion or multiple-lesion groups. A total of 41 lesions underwent
      implantation of from 8 to 106 125I seeds (median=43). Multi-plane implanting was
      adopted and 125I-seeds of (0.4-0.7)mCi were placed at intervals of (0.5-1.0) cm.
      After implantation treatment, all patients underwent 4 cycles of chemotherapy
      with gemcitabine 800 mg/m2 (days 1, 8 and 15). RESULTS: The outcome was evaluated
      with CT 3 weeks and every 3 months after implantation treatment. After 6 months,
      the volume of 32 out of 41 lesions (78.0%) was reduced at least 30%, within which
      9 lesions completely disappeared(22.0%). Complete response was observed in 7
      cases (30.4%), with a partial response in 4 cases (17.4%),4 cases
      stable(17.4%)and 8 cases showing progression (34.8%). The total clinical
      remission rate was 47.8% (11/23). The clinical remission rate was 77.8% (7/9) in
      the single-lesion group and 28.6% (4/14) in the multiple-lesion group with a
      significant difference between the two(P=0.036). The common side effects observed
      were mild gastrointestinal reactions. CONCLUSIONS: 125I-seed implantation
      combined with chemotherapy applies an effective way in the treatment of platinum
      resistant recurrent ovarian epithelial carcinoma with the advantages of high
      local control rates, good short-term effects, little trauma and less side
      effects.

PMID- 25374245
TI  - Influence of payer source on treatment and outcomes in colorectal cancer patients
      in a university hospital in Thailand.
AB  - The study aimed to compare the 2 main types of insurance used by colorectal
      cancer (CRC) patients in a university hospital in Thailand: universal coverage
      (UC) and 'Civil Servant Medical Benefit Scheme' (CSMBS) in terms of hospital
      expenditure and survival outcomes. CRC cases in stages I-IV who were operated on
      and had completed their adjuvant therapy in Songklanagarind Hospital from 2004
      through 2013 were retrospectively reviewed regarding their hospital expenditure,
      focusing on surgical and chemotherapy costs. Of 1,013 cases analyzed, 524 (51.7%)
      were in the UC group while 489 (48.3%) belonged to the CSMBS group. Cases with
      stage IV disease were significantly more frequent in the UC group. Average total
      treatment expenditure (TTE) was 143,780 Thai Baht (THB) (1 US$=~30 THB). The TTE
      increased with tumor stage and the chemotherapy cost contributed the most to the
      TTE increment. TTE in the CSMBS group was significantly higher than in the UC
      group for stage II-III CRCs. The majority of cases in the UC group (65.5%) used
      deGramont or Mayo as their first line regimen, and the proportion of cases who
      started with a capecitabine-based regimen (XELOX or Xeloda(r)) was significantly
      higher in the CSMBS group (61.0% compared to 24.5% in the UC group, p
      value<0.01). On survival analysis, overall survival (OS) and progress free
      survival in the CSMBS group were significantly better than in the UC group. The 5
      year OS in the CSMBS and UC groups were 84.3% and 74.6%, respectively (p
      value<0.01). In conclusion, the study indicates that in Thailand, the type of
      insurance influences resource utilization, especially the choice of chemotherapy,
      in CRC cases. This disparity in treatment, in turn, results in a gap in treatment
      outcomes.

PMID- 25374246
TI  - Predictors affecting breast self-examination practice among Turkish women.
AB  - BACKGROUND: Breast cancer (BC) is the most common cancer among females in Turkey.
      Predictors affecting the breast self-examination (BSE) performance vary in
      developing countries. OBJECTIVE: To determine the frequency of BSE performance
      and predictors of self-reported BSEs among women in the capital city of Turkey.
      MATERIALS AND METHODS: This cross-sectional study was conducted on 376 Turkish
      women using a self- administered questionnaire covering socio-demographic
      variables and BSE-related features. RESULTS: Of the participants, 78.7% (N=296)
      reported practicing BSE, whereas 9.5% (N=28) were implementing BSE regularly on a
      monthly basis, and only 5.7% (N=17) were performing BSE regularly within a week
      after each menstrual cycle. Multivariate logistic regression modeling revealed
      that BSE performance was more likely in younger age groups [20-39 years]
      (p=0.018, OR=3.215) and [40-49 years] (p=0.009, OR=3.162), women having a family
      history of breast disease (p=0.038, OR=2.028), and housewives (p=0.013,
      OR=0.353). CONCLUSIONS: Although it appears that the rates of BSE performers are
      high, the number of women conducting appropriate BSE on a regular time interval
      basis is lower than expected. Younger age groups, family history of breast
      diseases and not being employed were identified as significant predictors of
      practicing BSE appropriately. Older age and employment were risk factors for not
      performing BSE in this sample.

PMID- 25374247
TI  - Virulence genes of Helicobacter pylori in gastritis, peptic ulcer and gastric
      cancer in Laos.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) infection is an established cause of
      peptic ulcers and gastric cancer. The aim of this study was to identify H. pylori
      genotypes and to examine their associations with geographical regions and
      gastritis, peptic ulcers and gastric cancer in Laos. MATERIALS AND METHODS: A
      total of 329 Lao dyspeptic patients who underwent gastroscopy at Mahosot
      Hospital, Vientiane, Laos during December 2010--March 2012 were enrolled. Two
      biopsy specimens (one each from the antrum and corpus) were obtained for CLO
      testing and only CLO test-positive gastric tissue were used to extract DNA. PCR
      and sequencing were identified for variants of the cagA and vacA genotypes.
      RESULTS: Some 119 Laos patients (36.2%) were found to be infected with H. pylori
      including 83 with gastritis, 13 with gastric ulcers (GU), 20 with duodenal ulcers
      (DU) and 3 with gastric cancer. cagA was detected in 99.2%. East-Asian-type cagA
      (62%) and vacA s1c (64.7%) were predominant genotypes in Laos. vacA s1c-m1b was
      significantly higher in GU than gastritis (53.8% vs. 24.1%; P-value=0.04) whereas
      vacA s1a-m2 was significantly higher in DU than gastritis (40.0% vs. 16.9%; P
      value=0.03). East-Asian-type cagA and vacA s1c were significantly higher in
      highland than lowland Lao (100% vs. 55.8%; P-value=0.001 and 88.2% vs. 61.5%, P
      value=0.03 respectively). CONCLUSIONS: H. pylori is a common infection in Laos,
      as in other countries in Southeast Asia. The cagA gene was demonstrated in nearly
      all Laos patients, cagA and vacA genotypes being possible important factors in
      explaining H. pylori infection and disease outcomes in Laos.

PMID- 25374248
TI  - Feasibility study of deep inspiration breath-hold based volumetric modulated arc
      therapy for locally advanced left sided breast cancer patients.
AB  - BACKGROUND: The purpose of this study was to assess the feasibility of deep
      inspiration breath-hold (DIBH) based volumetric modulated arc therapy (VMAT) for
      locally advanced left sided breast cancer patients undergoing radical mastectomy.
      DIBH immobilizes the tumor bed providing dosimetric benefits over free breathing
      (FB). MATERIALS AND METHODS: Ten left sided post mastectomy patients were
      immobilized in a supine position with both the arms lifted above the head on a
      hemi-body vaclock. Two thermoplastic masks were prepared for each patient, one
      for normal free breathing and a second made with breath-hold to maintain
      reproducibility. DIBH CT scans were performed in the prospective mode of the
      Varian real time position management (RPM) system. The planning target volume
      (PTV) included the left chest wall and supraclavicular nodes and PTV prescription
      dose was 5000cGy in 25 fractions. DIBH-3DCRT planning was performed with the
      single iso-centre technique using a 6MV photon beam and the field-in-field
      technique. VMAT plans for FB and DIBH contained two partial arcs (179o
      300oCCW/CW). Dose volume histograms of PTV and OAR's were analyzed for DIBH-VMAT,
      FB-VMAT and DIBH-3DCRT. In DIBH mode daily orthogonal (0o and 90o) KV images were
      taken to determine the setup variability and weekly twice CBCT to verify gating
      threshold level reproducibility. RESULTS: DIBH-VMAT reduced the lung and heart
      dose compared to FB-VMAT, while maintaining similar PTV coverage. The mean heart
      V30Gy was 2.3% +/-2.7, 5.1% +/-3.2 and 3.3% +/-7.2 and for left lung V20Gy was
      18.57% +/-2.9, 21.7% +/-3.9 and 23.5% +/-5.1 for DIBH-VMAT, FB-VMAT and DIBH
      3DCRT respectively. CONCLUSIONS: DIBH-VMAT significantly reduced the heart and
      lung dose for left side chest wall patients compared to FB-VMAT. PTV conformity
      index, homogeneity index, ipsilateral lung dose and heart dose were better for
      DIBH-VMAT compared to DIBH-3DCRT. However, contralateral lung and breast volumes
      exposed to low doses were increased with DIBH-VMAT.

PMID- 25374249
TI  - Immunopreventive effects against murine H22 hepatocellular carcinoma in vivo by a
      DNA vaccine targeting a gastrin- releasing peptide.
AB  - There is a continuing need for innovative alternative therapies for liver cancer.
      DNA vaccines for hormone/ growth factor immune deprivation represent a feasible
      and attractive approach for cancer treatment. We reported a preventive effect of
      a DNA vaccine based on six copies of the B cell epitope GRP18-27 with optimized
      adjuvants against H22 hepatocarcinoma. Vaccination with pCR3.1-VS-HSP65-TP-GRP6
      M2 (vaccine) elicited much higher level of anti-GRP antibodies and proved
      efficacious in preventing growth of transplanted hepatocarcinoma cells. The tumor
      size and weight were significantly lower (p<0.05) in the vaccine subgroup than in
      the control pCR3.1-VS-TP-HSP65-TP-GRP6, pCR3.1-VS-TP-HSP65-TP-M2 or saline
      subgroups. In addition, significant reduction of tumor-induced angiogenesis
      associated with intradermal tumors of H22 cells was observed. These potent
      effects may open ways towards the development of new immunotherapeutic approaches
      in the treatment of liver cancer. 

PMID- 25374250
TI  - Drugs from marine sources: modulation of TRAIL induced apoptosis in cancer cells.
AB  - There have been overwhelming advances in molecular oncology and data obtained
      through high-throughput technologies have started to shed light on wide ranging
      molecular mechanisms that underpin cancer progression. Increasingly it is being
      realized that marine micro-organisms and the biodiversity of plankton are rich
      sources of various anticancer compounds. Marine derived compounds play major
      roles in inducing apoptosis in cancer cells. More importantly, various agents
      have been noted to enhance TRAIL induced apoptosis in cancer cells by
      functionalizing intrinsic and extrinsic pathways. In this commentary, a list of
      marine derived compounds reported to induce apoptosis is discussed. 

PMID- 25374251
TI  - Ganoderma lucidum inhibits proliferation of human ovarian cancer cells by
      suppressing VEGF expression and up-regulating the expression of connexin 43.
AB  - BACKGROUND: Ganoderma lucidum (G. lucidum, Reishimax) is an herbal mushroom known
      to have inhibitory effect on tumor cell growth. However, the molecular mechanisms
      responsible for its anti-proliferative effects on the ovarian cancer have not
      been fully elucidated. METHODS: Human ovarian cancer cells HO 8910 (HOCC) and
      human primary ovarian cells (HPOC) were treated with G. lucidum. Effects of G.
      lucidum treatment on cell proliferation were studied by MTT assay. The expression
      of vascular endothelial growth factor (VEGF) and connexin 43 (Cx43) were measured
      by immunohistochemistry and real time polymerase chain reaction. To study the
      molecular mechanism of CX43 mediated anti-tumor activity, small interference RNA
      (siRNA) was used to knockdown Cx43 expression in HOCC. RESULTS: G. lucidum
      treatment resulted in reduced proliferation of HOCC. Inhibition of proliferation
      was accompanied by a decrease in VEGF expression and increase in Cx43 expression
      in the cancer cells. The extent of immune-reactivity of Cx43 or VEGF in cancer
      cells were correlated with the concentrations of G. lucidum used for treatment.
      Furthermore, knockdown of Cx43 expression in HOCC abrogated the effect of G.
      lucidum on cell proliferation without alteration of G. lucidum-induced
      attenuation of VEGF expression. CONCLUSIONS: G. lucidum inhibits ovarian cancer
      by down-regulating the expression of VEGF and up-regulating the downstream Cx43
      expression. G. lucidum may be a promising therapeutic agent for the treatment of
      ovarian cancer.

PMID- 25374252
TI  - Prostatectomy for localized prostate cancer to prepare for renal transplantation
      in end-stage renal disease patients.
AB  - BACKGROUND: Surgical difficulties of renal transplantation related to prostate
      cancer (PC) treatment and the results of renal transplantation after radical
      prostatectomy are currently poorly known, as well as oncological follow-up before
      and after renal transplantation. MATERIAL/METHODS: We performed a retrospective
      study including all patients diagnosed with PC before renal transplantation in
      our department. RESULTS: Nineteen patients were included between August 2003 and
      December 2013. The mean age at diagnosis of PC was 61.7 years (range 51.4-71.1).
      PSA mean level at diagnosis was 8.5 ng/ml (range 4.8-20). Fourteen had a retro
      pubic and 5 a laparoscopic prostatectomy. Three patients underwent radiotherapy
      for positive surgical margins or extra-capsular extension. Fourteen patients were
      transplanted. The mean time lapse between prostatectomy and kidney
      transplantation was 32.8 months (range 14-71). Seven recipients (50%) were
      transplanted less than 24 months after prostatectomy. Post-transplantation
      surgical complications were not significantly related to dissection difficulties
      (p=0.2). No recurrence of PC was observed after renal transplantation, with a
      mean follow-up of 38 months (range 6-77.9). CONCLUSIONS: Prostate cancer
      discovered before renal transplantation should be treated by radical
      prostatectomy to assess recurrence risk. If the PC is at low risk of recurrence,
      it seems possible to shorten the 2-year period of oncologic follow-up before
      transplantation called for in current recommendations.

PMID- 25374253
TI  - A case of bilateral tracheal bronchus: report of a rare association in
      multidetector computed tomography bronchoscopy.
AB  - Bilateral tracheal bronchus is a rare variation of the tracheobronchial tree. We
      present a 1-year 7-month-old male patient who presented with sepsis following
      endotracheal intubation. Upon review of multidetector computed tomography images,
      the patient was diagnosed with displaced bilateral tracheal bronchus. Imaging
      showed a right-sided anomalous bronchus arising 0.9 cm proximal to the carina.
      The left-sided anomalous bronchus arose 0.7 cm proximal to the carina, mimicking
      a tracheal trifurcation. When viewed together, the close proximity of both the
      right and left tracheal bronchi to the carina created a distinct tracheal
      quadrifurcation. This rare anatomic variation was additionally associated with an
      anorectal malformation (anal atresia). Unrecognized tracheal bronchus in patients
      undergoing endotracheal intubation can lead to serious complications. While
      bilateral tracheal bronchus is described in the literature, we are unaware of any
      case similar to this patient presentation. We present and analyze this unusual
      case of bilateral tracheal bronchus. The anatomy and clinical significance of
      this variation is then discussed.

PMID- 25374255
TI  - Dynamic vibrotactile warning signals for frontal collision avoidance: towards the
      torso versus towards the head.
AB  - Three experiments were conducted to assess the effectiveness of dynamic
      vibrotactile warning signals with different spatial patterns and to compare
      dynamic towards-torso and towards-head vibrotactile warnings in a simulated
      driving task. The results revealed that embedding additional stimuli between the
      participant's hands and waist in the towards-torso cues (Experiment 1) and
      increasing the spatial distance between adjacent stimuli in the towards-head cues
      (Experiment 2) did not result in any further benefits in braking response times
      (BRTs). The triple towards-head cues resulting from the sequential operation of
      three pairs of stimuli on the torso gave rise to a significant advantage over the
      static cues; however, it did not outperform the dynamic towards-torso cues with
      just two pairs of stimuli. Taken together, these results demonstrated the promise
      of dynamic vibrotactile warnings (especially, the towards-torso warnings) in
      terms of the future design of more effective rear-end collision warnings.
      PRACTITIONER SUMMARY: Three experiments assessed the effectiveness of dynamic
      towards-torso and towards-head vibrotactile warning signals in a simulated
      driving task. The results demonstrated the promise of dynamic vibrotactile
      warnings (especially, the towards-torso vibrotactile warnings) in terms of the
      future design of more effective frontal collision warnings.

PMID- 25374254
TI  - Phosphorylation in intrinsically disordered regions regulates the activity of
      Neurogenin2.
AB  - BACKGROUND: Neuronal differentiation is largely under the control of basic Helix
      Loop-Helix (bHLH) proneural transcription factors that play key roles during
      development of the embryonic nervous system. In addition to well-characterised
      regulation of their expression, increasing evidence is emerging for additional
      post-translational regulation of proneural protein activity. Of particular
      interest is the bHLH proneural factor Neurogenin2 (Ngn2), which orchestrates
      progression from neural progenitor to differentiated neuron in several regions of
      the central nervous system. Previous studies have demonstrated a key role for
      cell cycle-dependent multi-site phosphorylation of Ngn2 protein at Serine-Proline
      (SP) sites for regulation of its neuronal differentiation activity, although the
      potential structural and functional consequences of phosphorylation at different
      regions of the protein are unclear. RESULTS: Here we characterise the role of
      phosphorylation of specific regions of Ngn2 on the stability of Ngn2 protein and
      on its neuronal differentiation activity in vivo in the developing embryo,
      demonstrating clearly that the location of SP sites is less important than the
      number of SP sites available for control of Ngn2 activity in vivo. We also
      provide structural evidence that Ngn2 contains large, intrinsically disordered
      regions that undergo phosphorylation by cyclin-dependent kinases (cdks).
      CONCLUSIONS: Phosphorylation of Ngn2 occurs in both the N- and C-terminal
      regions, either side of the conserved basic Helix-Loop-Helix domain. While these
      phosphorylation events do not change the intrinsic stability of Ngn2,
      phosphorylation on multiple sites acts to limit its ability to drive neuronal
      differentiation in vivo. Phosphorylated regions of Ngn2 are predicted to be
      intrinsically disordered and cdk-dependent phosphorylation of these intrinsically
      disordered regions contributes to Ngn2 regulation.

PMID- 25374256
TI  - CYP3A4-based drug-drug interaction: CYP3A4 substrates' pharmacokinetic properties
      and ketoconazole dose regimen effect.
AB  - The aim of the study was to assess the magnitude of the CYP3A4 inhibitory effect
      of 2 dosing regimens of ketoconazole and the influence of the pharmacokinetic
      properties of the CYP3A4 substrate on the extent of the substrate exposure
      increase. For this purpose, a clinical study was conducted and PBPK modeling
      simulations were performed. A crossover study was conducted in healthy subjects.
      The study was designed to compare the effects of different regimens of reversible
      CYP3A4 inhibitors, i.e., ketoconazole 400 mg OD, ketoconazole 200 mg BID, on two
      CYP3A4 substrates, alprazolam and midazolam, reflecting different pharmacokinetic
      properties in terms of first-pass effect and elimination. In parallel, time-based
      simulations were performed using the Simcyp population-based Simulator to address
      the usefulness of modeling to assess interaction clinical study design with
      CYP3A4 substrates. Comparison of the OD versus BID regimens for ketoconazole
      showed an opposite trend for the 2 substrates: BID (200 mg) dosing regimen
      provided the maximal clearance inhibition for alprazolam, while it was OD (400
      mg) dosing regimen for midazolam. However, these effects are moderate despite the
      well-known pharmacokinetic differences between these substrates, suggesting that
      these differences are not enough. In the other way round, these investigations
      show how two CYP3A4 substrates can be different without leading to a major impact
      of the ketoconazole dosing regimen. The clinical findings are consistent with the
      Simcyp predictions, in particular the opposite trend observed with midazolam and
      alprazolam and the ketoconazole dosing regimen. These clinical investigations
      showed the influence of the CYP3A4 substrates' pharmacokinetic properties and the
      relevance of ketoconazole dose regimen on the magnitude of the interaction
      ratios. In addition, PBPK Simcyp simulations demonstrated how they can be used to
      help clinical study design assessment to capture the maximum effect.

PMID- 25374258
TI  - Oestrus synchronisation in postpartum dairy cows using repetitive prostaglandin
      doses: Comparison between D-cloprostenol and dinoprost.
AB  - This trial evaluated the reproductive performance in an early routine oestrus
      induction programme using two different PGF2alpha preparations in dairy cattle. D
      cloprostenol sodium (n = 192; Group A) or dinoprost (n = 187; Group B) was
      administered between days 35 and 42 post partum. Also, a group of non-treated
      cows (n = 135; Group C) was included as control. Pedometers were used to detect
      oestrus, and also secondary oestrous signs and vaginal mucus quality were
      assessed prior to artificial insemination (AI). When oestrus was not detected for
      14 days after PGF2alpha administration, the treatment was repeated, up to a
      maximum of three times. There were no differences between the study groups in
      oestrus detection (A = 73.48%, B = 73.01%, C = 79.26%; P = 0.428), good mucus
      quality (A = 96.45%, B = 91.30%, C = 93.45%; P = 0.203) and the presence of
      mounting lesions (A = 98.58, B = 94.93%, C = 98.13; P = 0.414). First-service
      pregnancy rates were 19.78%, 15.64% and 32.03% in Groups A, B and C, respectively
      (P = 0.003). There were no inter-group differences for the interval from
      parturition to first AI. However, a significantly shorter interval from
      parturition to conception (92.17 days, 99.45 days, 118.93 days; P = 0.002) and
      significantly less services per conception (2.12, 2.18, 2.66; P = 0.003) were
      observed in Groups A and B in comparison with Group C. The use of PGF2alpha
      resulted in better fertility in a repetitive, routine postpartum programme,
      although no differences between Dcloprostenol and dinoprost were detected. 

PMID- 25374257
TI  - The relative contribution of layers of the Social Ecological Model to childhood
      obesity.
AB  - OBJECTIVE: The Social Ecological Model (SEM) has been used to describe the
      aetiology of childhood obesity and to develop a framework for prevention. The
      current paper applies the SEM to data collected at multiple levels, representing
      different layers of the SEM, and examines the unique and relative contribution of
      each layer to children's weight status. DESIGN: Cross-sectional survey of
      randomly selected households with children living in low-income diverse
      communities. SETTING: A telephone survey conducted in 2009-2010 collected
      information on parental perceptions of their neighbourhoods, and household,
      parent and child demographic characteristics. Parents provided measured height
      and weight data for their children. Geocoded data were used to calculate
      proximity of a child's residence to food and physical activity outlets. SUBJECTS:
      Analysis based on 560 children whose parents participated in the survey and
      provided measured heights and weights. RESULTS: Multiple logistic regression
      models were estimated to determine the joint contribution of elements within each
      layer of the SEM as well as the relative contribution of each layer. Layers of
      the SEM representing parental perceptions of their neighbourhoods, parent
      demographics and neighbourhood characteristics made the strongest contributions
      to predicting whether a child was overweight or obese. Layers of the SEM
      representing food and physical activity environments made smaller, but still
      significant, contributions to predicting children's weight status. CONCLUSIONS:
      The approach used herein supports using the SEM for predicting child weight
      status and uncovers some of the most promising domains and strategies for
      childhood obesity prevention that can be used for designing interventions.

PMID- 25374259
TI  - Profile of toll-like receptor mRNA expression in the choroid plexus in adult
      ewes.
AB  - The blood-cerebrospinal fluid barrier (BCSFB) located in the epithelial cells of
      the choroid plexus (CP) forms the interface between the cerebrospinal fluid (CSF)
      and pathogen components circulating in the blood. The CP is also implicated in
      the passage of peripheral immune signals and circulation of immune cells into the
      central nervous system. Toll-like receptors (TLRs) are patternrecognition
      receptors that play a crucial role in the recognition of pathogens and triggering
      of the innate immune response. In sheep, ten members of the TLR family have been
      identified and cloned. We used real-time PCR analyses to examine the profiles of
      TLR mRNA expression in the CP of cerebral ventricles in healthy adult ewes. The
      transcripts for all ten TLRs except TLR8 were present; however, we observed a
      high variation in the degree of expression of the TLR5 and TLR1 genes
      (coefficient of variation: 61% and 46%, respectively) as well as a moderate
      variation in the expression of the TLR4 (34%), TLR2 (27%) and TLR6 (26%) genes.
      The TLR9, TLR7, TLR3 and TLR10 genes were the four receptors with relatively
      invariable expression levels (coefficient of variation: 7%, 8%, 16% and 17%,
      respectively) across the six adult ewes. The concentration of cortisol in blood
      collected prior to sacrificing the ewes ranged from 0.18 to 78.9 ng/ml. There was
      no correlation between cortisol concentration and mRNA expression of any of the
      examined TLRs. These data suggest that the CP has the potential to sense the
      presence of many bacterial and viral components and mediate responses for the
      elimination of invading microorganisms, thereby protecting the brain. 

PMID- 25374260
TI  - Comparison of estimated GFR and measured GFR in prospective living kidney donors.
AB  - PURPOSE: The aim of this study was to examine the usefulness of three GFR
      estimating equations (eGFR) compared with measured GFR (mGFR) in potential living
      kidney donors. METHODS: We compared the performance of the MDRD, CKD-Epi and
      Cockcroft-Gault equations with mGFR measured using (51)Cr-EDTA in 508 consecutive
      potential living kidney donors. Each equation was assessed for bias, precision
      and accuracy compared with mGFR, and the sensitivity and specificity for the
      identification of donors with mGFR<80 mL/min/1.73 m2 was evaluated. RESULTS: Two
      hundred and forty-four subjects were male, 398 Caucasian, 60 Afro-Caribbean and
      50 from other ethnic groups. Median age and mGFR were 44.1 year and 91.7
      mL/min/1.73 m2, respectively. Spearman correlation coefficients between eGFR and
      mGFR were in the range R s=0.520-0.593. Median bias (eGFR-mGFR) for the MDRD, CKD
      Epi and Cockcroft-Gault equations were -1.0 (p=0.98), +8.8 (p<0.0001) and +11.1
      (p<0.0001) mL/min/1.73 m2, respectively. Significant differences in bias between
      Afro-Caribbean and Caucasian subjects were found. The sensitivity (specificity)
      for the MDRD, CKD-Epi and Cockcroft-Gault equations for identifying subjects with
      mGFR<80 mL/min/1.73 m2 was 60 (83), 39 (95) and 44% (95%), respectively.
      CONCLUSIONS: The level of agreement between mGFR and all three eGFR values was
      poor, with the MDRD equation performing best. We conclude that reliance on
      creatinine-based eGFR values is unsatisfactory for the evaluation of potential
      living kidney donors.

PMID- 25374261
TI  - Total urinary tract exenteration including donor nephrectomy for transitional
      cell carcinoma 41 years following transplantation.

PMID- 25374262
TI  - Intermittent voiding per urethra as an indicator of cutaneous vesicostomy
      malfunction.
AB  - PURPOSE: To present a new approach for management of cutaneous vesicostomy (CV)
      prolapse, with special emphasis on normal appearing vesicostomy may be
      malfunctioning. To introduce the application of temporary stoma-free drainage as
      a diagnostic and therapeutic tool. MATERIALS AND METHODS: From December 2000 to
      September 2006, 66 children (61 males and 5 females) with CV were studied. The
      mean age at vesicostomy was 7 months (range 1-30), and the main underlying
      disease was posterior urethral valves (in 45 children, 68%). Indications for CV
      included significant hydroureteronephrosis (HUN) and recurrent urinary tract
      infection. Patients were followed up for complications and were treated based on
      our institutional approach. All patients with persistent upper tract dilatation
      and micturition per urethra underwent temporary bladder (via stoma) free
      drainage. Patients with stomal stenosis were managed either by a revision surgery
      or by simple dilatation and intermittent catheterization. Purse string suturing
      was applied in mucosal prolapses as the first choice. RESULTS: The complications
      were observed in 21 patients (31%), including twelve stomal stenosis, nine severe
      mucosal prolapses, and two recurrent urinary infections. HUN and significant
      voiding per urethra persisted following initial CV in 19 out of 66 patients
      (29%), eleven of which having normal appearing CVs. Seventeen of these patients
      were managed by temporary stoma-free drainage (accompanied by purse string
      suturing in mucosal prolapse), and two patients with severe stenosis underwent
      surgical revision. Temporary stoma-free drainage improved HUN in 94% of patients
      (16 of 17). CONCLUSIONS: Voiding per urethra is an indicator of CV malfunction,
      and temporary stoma-free drainage can be a diagnostic and therapeutic option in
      such children. A seemingly open CV may still be malfunctioning, and
      ureterovesical or intravesical obstructions should be considered if HUN does not
      improve following temporary stoma-free drainage.

PMID- 25374264
TI  - Calixarene-based extraction chromatographic separation of 135Cs and 137Cs in
      environmental and waste samples prior to sector field ICP-MS analysis.
AB  - Advances in the sensitivities achievable by sector field inductively coupled
      plasma mass spectrometry (ICP-SFMS) offer the prospect of low-level measurement
      of shorter and longer lived radionuclides, thus expanding options for
      environmental and radioactively contaminated land assessment. In ICP-SFMS, the
      critical requirement for accurate detection is the effective chemical separation
      of isobaric and polyatomic interferences prior to sample introduction. As
      instrumental detection limit capability improves, accurate radionuclide
      determination requires highly effective separation materials that combine high
      analyte selectivity with subsequent quantitative analyte recovery compatible with
      ICP-SFMS detection. Two radioactive isotopes measurable by ICP-SFMS are the high
      yield fission products (135)Cs and (137)Cs that have entered the environment as a
      result of anthropogenic nuclear activities. ICP-SFMS enables reliable measurement
      of (135)Cs/(137)Cs ratios, which can be used as a forensic tool in determining
      the source of nuclear contamination. The critical requirement for accurate
      detection is the effective removal of isobaric interferences from (135)Ba and
      (137)Ba prior to measurement. A number of exchange materials can effectively
      extract Cs; however, non-quantitative elution of Cs makes subsequent ICP-SFMS
      quantification challenging. A novel extraction chromatographic resin has been
      developed by dissolving calix[4]arene-bis(tert-octylbenzo-crown-6) (BOBCalixC6)
      in octan-1-ol and loading onto an Amberchrom CG-71 prefilter resin material.
      Preparation of the material takes less than 1 h and, at an optimal concentration
      of 3 M HNO3, shows high selectivity toward Cs, which is effectively eluted in
      0.05 M HNO3. The procedure developed shows high Cs selectivity and Ba
      decontamination from digests of complex matrixes including a saltmarsh sediment
      contaminated by aqueous discharges from a nuclear fuel reprocessing facility.
      Repeated tests show the resin can be reused up to four times. For low-level ICP
      SFMS quantification, more complex sample matrixes benefit from a cation resin
      cleanup stage prior to using BOBCalixC6 that serves to enhance Ba decontamination
      and Cs recovery. 

PMID- 25374263
TI  - A comparison between transabdominal ultrasonographic and cystourethroscopy
      findings in adult Sudanese patients presenting with haematuria.
AB  - PURPOSE: Gross and microscopic haematuria both are a common cause of referral to
      urology clinics. It has a wide spectrum of differential. In many occasions, it is
      a presentation of underlining serious urological problems. Evaluation of gross
      and significant microscopic haematuria is of paramount importance. This study was
      conducted to assess and compare the findings and diagnostic competency of
      transabdominal ultrasonography (US) versus cystourethroscopy in patients with
      haematuria of lower urinary tract origin. METHODS: Prospective hospital-based
      study done at Ibn Sina Specialized and Omdurman Military Hospitals from June 2012
      to March 2013. The study included 109 patients. Structured questionnaires were
      used to gather data from patients. All patients were evaluated by transabdominal
      US before cystourethroscopy examination. RESULTS: One hundred and nine patients
      were studied. Patients' mean (SD) age was 57.9 (18.8) years. Fifty-four patients
      (49.5 %) presented with macroscopic haematuria, while 55 patients presented with
      microscopic haematuria. The sensitivity and specificity of the US in detecting
      prostate enlargement, vesical stones, bladder wall tumour, cystitis and
      schistosomiasis were [(84, 80 %); (82.6, 97.7 %); (64.7, 92.1 %); (15.3, 96.8 %);
      and (15.3, 98.9 %)], respectively, as compared to cystoscopic finding as the gold
      standard. CONCLUSIONS: Ultrasonography is accepted only as a first-line imaging
      tool for evaluation of haematuria in poor settings, but cannot replace or became
      as good as cystoscopy, which remains the gold standard.

PMID- 25374265
TI  - Knowledge and attitude towards child marriage practice among women married as
      children-a qualitative study in urban slums of Lahore, Pakistan.
AB  - BACKGROUND: Child marriage (<18 years) is prevalent in Pakistan which is
      associated with negative health outcomes. Our aim is to describe women's
      knowledge and attitude towards child marriage practice who themselves were
      married as children. METHODS: Women of reproductive age (15-49 years) who were
      married prior to 18 years, for at least 5 years and had at least one child birth
      were recruited from most populous slum areas of Lahore, Pakistan. Themes for the
      interview were developed using published literature and everyday observations of
      the researchers. Interviews were conducted by trained interviewers in Urdu
      language and were translated into English. The interviews were tape-recorded,
      transcribed, analyzed and categorized into themes. RESULTS: Nineteen of 20
      participants who agreed to participate were married between 11-17 years. Most
      respondents were uneducated, poor and were working as housemaids. The majority
      participants were unaware of the negative health outcomes of child marriages.
      They appeared satisfied by the decision of their parents of marrying them before
      18 years, and even condemned banning child marriages in Pakistan. Strong
      influence of culture and community perceptions, varying interpretation of
      religion, and protecting family honor are some of the reasons that were narrated
      by the participants, which seems playing a role in continuation of child marriage
      practice in Pakistan. CONCLUSION: Raising awareness of the negative health
      outcomes of child marriage, implementing and enforcing strict laws against child
      marriage practice, promoting civil, sexual and reproductive health rights for
      women, can help eliminate child marriages in Pakistan.

PMID- 25374266
TI  - Clinical implications of MTA proteins in human cancer.
AB  - Metastasis-associated gene or metastasis tumor antigen 1 (MTA1) is a new member
      of cancer progression-related gene family. It was first identified in rat mammary
      adenocarcinoma and later recognized as an important constituent of nucleosomal
      remodeling complex (NuRD), displaying dual regulatory functions as a co-repressor
      and co-activator for a large number of genes. Chromatin remodelers are ATP
      dependent multi-protein chromatin modifying machines. These complexes alter the
      nucleosome positioning regulating the accessibility of genomic DNA to various
      transcription factors and thus modulate eukaryotic gene transcription. Since its
      identification two decades ago, MTA1 has been reported to be overexpressed in
      many cancers. Moreover, its overexpression has also been correlated with
      transformation and tumor progression. Furthermore, MTA1 has been shown to
      modulate the response of several tumor suppressor genes like p53 and oncogenes
      like c-myc. Taken together, current literature suggests that MTA proteins,
      especially MTA1, act as a master co-regulatory molecule involved in the
      carcinogenesis and progression of various malignant tumors. The primary focus of
      this review is to provide an overview of the MTA proteins with special emphasis
      on its role in cancer and use as a marker for cancer progression and potential
      target for therapy. 

PMID- 25374267
TI  - Signalling: uncovering new functions of PI3K mutations.

PMID- 25374268
TI  - EP217609, a neutralisable dual-action FIIa/FXa anticoagulant, with antithrombotic
      effects in arterial thrombosis.
AB  - EP217609 is a new synthetic parenteral dual-action anticoagulant combining a
      direct thrombin inhibitor (alpha-NAPAP analog), an indirect factor Xa inhibitor
      (fondaparinux analog) and a biotin moiety allowing its neutralisation. EP217609
      exhibited similar in vitro anticoagulant properties as its parent compounds. On
      the basis of dose-response curves, we identified low and moderate doses of
      EP217609 resulting in similar ex vivo prolongation of the APTT as alpha-NAPAP
      analog and comparable ex vivo anti-FXa activity as fondaparinux. The effects of
      EP217609 were compared to those of its parent compounds used alone or in
      combination in two models of experimental thrombosis induced by FeCl3 injury of
      the carotid artery or mechanical injury of atherosclerotic plaques in ApoE
      deficient mice. When administered at low doses increasing the APTT by only 1.1
      fold, EP217609 significantly reduced the thrombus area in both models as compared
      to alpha-NAPAP analog or fondaparinux alone, but not to the combination of these
      drugs. In contrast, at higher doses increasing the APTT 1.5 times, EP217609 was
      not superior to either parent compound. Low doses of EP217609 did not prolong the
      tail bleeding time or increase the volume of blood loss, although a tendency
      towards an increased blood loss was observed in five out of 12 mice. Finally, the
      effects of EP217609 could be neutralised in vivo by injection of avidin. The
      pharmacological profile of EP217609, its performance in arterial thrombosis
      models and its possible neutralisation make it an interesting molecule and a
      potential candidate as an antithrombotic drug. 

PMID- 25374269
TI  - Men's knowledge and attitudes towards dietary prevention of a prostate cancer
      diagnosis: a qualitative study.
AB  - BACKGROUND: Prostate cancer (PC) incidence and progression may be influenced by
      dietary factors, but little is known about the acceptability of dietary
      modification to men at increased risk of PC. Qualitative interviews with men
      participating in the ProDiet study were undertaken to explore the feasibility of
      implementing dietary interventions for the prevention of prostate cancer.
      METHODS: An interview study nested within the ProDiet randomised feasibility
      trial of dietary interventions to prevent a PC diagnosis. Men (n = 133) who
      previously participated in community based prostate specific antigen (PSA)
      testing without PC but who were at increased risk of the disease were randomly
      allocation to both lycopene (lycopene or placebo capsules or lycopene rich diet)
      and green tea (green tea or placebo capsules or green tea drink) for 6 months.
      Semi-structured interviews were conducted with participants shortly after
      randomisation, to investigate attitudes towards dietary modification for PC
      prevention and dietary information. Interviews were audio-recorded, transcribed
      and analysed to identify common themes. RESULTS: Interviews were conducted with
      21 participants aged 52-72 years with PSA levels between 2.5 and 2.95 ng/ml, or a
      negative prostate biopsy result. Most men identified the major causes of cancer
      in general to include diet, environment, ageing and genetic factors. This
      contrasted sharply with men's uncertainty about PC aetiology, and the function of
      the prostate. Men were confused by conflicting messages in the media about
      dietary practices to promote health overall, but were positive about the
      potential of lycopene and green tea in relation to PC prevention, valuing their
      natural components. Furthermore these men wanted tailored dietary advice for PC
      prevention from their clinicians, whom they considered a trusted source of
      information. CONCLUSION: Men at elevated risk of PC reported uncertainty about PC
      aetiology and the role of diet in PC prevention, but enthusiasm for dietary
      modifications that were perceived as 'simple' and 'natural'. The men looked to
      clinicians to provide consistent disease specific dietary advice. These factors
      should be taken into consideration by clinicians discussing elevated PSA results
      with patients and those planning to embark on future trials investigating dietary
      modification interventions for the prevention of a PC diagnosis.

PMID- 25374270
TI  - The impact of surgical resection of giant supratentorial brain tumor in pediatric
      patients: safety and neurological outcome evaluated in 23 consecutive cases.
AB  - OBJECTIVE: This study aims to evaluate the impact of gross total resection of
      giant supratentorial brain tumors (GSBT) on survival and neurological outcome in
      a consecutive single-center pediatric series. METHODS: Clinical data of 23
      patients under 18 years of age operated with GSBT (>=5 cm in diameter) were
      reviewed to determine epidemiological aspects, clinical presentation, associated
      factors, histopathological features, and outcome. Volumetric measurements were
      performed on magnetic resonance imaging or computed tomography scans obtained at
      the time of the initial surgical procedure. RESULTS: The group included 23
      patients (mean age 4.5 years). Signs and symptoms of raised intracranial pressure
      were present in 19 patients (82.6%). The most frequent tumor location was the
      parietal lobe in 19 patients (82.6%), and the mean tumor volume was 208 cm(3).
      Gross total or radical resection was achieved in all patients. Histopathological
      analysis revealed malignant brain tumors in 18 cases (78.2%). The most common
      neoplasm was choroid plexus carcinoma in seven (30.4 %). Mean intraoperative
      blood transfusion volume was 51.2 ml/kg. Chemotherapy and/or radiotherapy were
      performed as adjuvant treatment in 16 patients (69.5%). Mean length of follow-up
      was 36.7 months. Tumor malignancy grade significantly correlated with recurrence
      of the disease (P = 0.03) and death (P = 0.01), as opposed to tumor location,
      size, and extension to the ventricles. CONCLUSIONS: Our clinical experience
      suggests that tumor mass reduction by en bloc surgery seems to be an effective
      approach in pediatric patients with GSBT, relieving symptoms related to raised
      intracranial pressure and providing a better response to adjuvant treatment.

PMID- 25374271
TI  - Decline in verbal fluency after subthalamic nucleus deep brain stimulation in
      Parkinson's disease: a microlesion effect of the electrode trajectory?
AB  - BACKGROUND: Decline in verbal fluency (VF) is frequently reported after chronic
      deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson
      disease (PD). OBJECTIVE: We investigated whether the trajectory of the implanted
      electrode correlate with the VF decline 6 months after surgery. METHODS: We
      retrospectively analysed 59 PD patients (mean age, 61.9 +/- 7; mean disease
      duration, 13 +/- 4.6) who underwent bilateral STN-DBS. The percentage of VF
      decline 6 months after STN-DBS in the on-drug/on-stimulation condition was
      determined in respect of the preoperative on-drug condition. The patients were
      categorised into two groups (decline and stable) for each VF. Cortical entry
      angles, intersection with deep grey nuclei (caudate, thalamic or pallidum), and
      anatomical extent of the STN affected by the electrode pathway, were compared
      between groups. RESULTS: A significant decline of both semantic and phonemic VF
      was found after surgery, respectively 14.9% +/- 22.1 (P < 0.05) and 14.2% +/-
      30.3 (P < 0.05). Patients who declined in semantic VF (n = 44) had a left
      trajectory with a more anterior cortical entry point (56 +/- 53 versus 60 +/- 55
      degree, P = 0.01) passing less frequently trough the thalamus (P = 0.03).
      CONCLUSIONS: Microlesion of left brain regions may contribute to subtle cognitive
      impairment following STN-DBS in PD.

PMID- 25374272
TI  - Effects of endurance exercise training on the motor and non-motor features of
      Parkinson's disease: a review.
AB  - BACKGROUND: Despite the benefits of medications and surgical interventions for
      Parkinson's disease (PD), these treatments are not without complications and
      neuroprotective strategies are still lacking. Therefore, there is a need for
      effective alternative approaches to treat motor and non-motor symptoms in PD.
      During the last decade, several studies have investigated endurance exercise
      training as a potential treatment for individuals with PD. OBJECTIVE: This paper
      reviews the therapeutically beneficial effects of endurance exercise training on
      motor and non-motor symptoms in PD. METHODS: First, we performed a systematic
      review of the literature on the effects of endurance exercise training on motor
      and non-motor signs of parkinsonism, functional outcomes including gait, balance
      and mobility, depression and fatigue, quality of life and perceived patient
      improvement, cardiorespiratory function, neurophysiological measures, and motor
      control measures in PD. Second we performed a meta-analysis on the motor section
      of the UPDRS. Then, we focused on several important factors to consider when
      prescribing endurance exercise training in PD such as intensity, duration,
      frequency, specificity and type of exercise. In addition, we identified current
      knowledge gaps regarding endurance exercise training in PD and made suggestions
      for future research. RESULTS: A total of eight randomized controlled trials met
      the inclusion criteria and were reviewed. This systematic review synthesizes
      evidence that endurance exercise training at a sufficiently high level enhances
      cardiorespiratory capacity and endurance by improving VO2 max and gait in
      moderately to mildly affected individuals with PD. However, there is not yet a
      proven effect of endurance exercise training on specific features of PD such as
      motor signs of parkinsonism. CONCLUSION: Endurance exercise training improves
      physical conditioning in PD patients; however, to date, there is insufficient
      evidence to include endurance exercise training as a specific treatment for PD.
      There is a need for well-designed large-scale randomized controlled trials to
      confirm benefits and safety of endurance exercise training in PD and to explore
      potential benefits on the motor and non-motor signs of PD.

PMID- 25374273
TI  - Note on evaluating safety performance of road infrastructure to motivate safety
      competition.
AB  - Road infrastructures are usually developed and maintained by governments or
      public sectors. There is no competitor in the market of their jurisdiction. This
      monopolic feature discourages road authorities from improving the level of safety
      with proactive motivation. This study suggests how to apply a principle of
      competition for roads, in particular by means of performance evaluation. It first
      discusses why road infrastructure has been slow in safety oriented development
      and management in respect of its business model. Then it suggests some practical
      ways of how to promote road safety between road authorities, particularly by
      evaluating safety performance of road infrastructure. These are summarized as
      decision of safety performance indicators, classification of spatial boundaries,
      data collection, evaluation, and reporting. Some consideration points are also
      discussed to make safety performance evaluation on road infrastructure lead to
      better road safety management. 

PMID- 25374274
TI  - Ciliary dysfunction impairs beta-cell insulin secretion and promotes development
      of type 2 diabetes in rodents.
AB  - Type 2 diabetes mellitus is affecting more than 382 million people worldwide.
      Although much progress has been made, a comprehensive understanding of the
      underlying disease mechanism is still lacking. Here we report a role for the beta
      cell primary cilium in type 2 diabetes susceptibility. We find impaired glucose
      handling in young Bbs4(-/-) mice before the onset of obesity. Basal body/ciliary
      perturbation in murine pancreatic islets leads to impaired first phase insulin
      release ex and in vivo. Insulin receptor is recruited to the cilium of stimulated
      beta-cells and ciliary/basal body integrity is required for activation of
      downstream targets of insulin signalling. We also observe a reduction in the
      number of ciliated beta-cells along with misregulated ciliary/basal body gene
      expression in pancreatic islets in a diabetic rat model. We suggest that ciliary
      function is implicated in insulin secretion and insulin signalling in the beta
      cell and that ciliary dysfunction could contribute to type 2 diabetes
      susceptibility. 

PMID- 25374276
TI  - Erratum to: Feature ranking of type 1 diabetes susceptibility genes improves
      prediction of type 1 diabetes.

PMID- 25374275
TI  - Mechanisms underlying weight loss and metabolic improvements in rodent models of
      bariatric surgery.
AB  - Obesity is a growing health risk with few successful treatment options and fewer
      still that target both obesity and obesity-associated comorbidities. Despite
      ongoing scientific efforts, the most effective treatment option to date was not
      developed from basic research but by surgeons observing outcomes in the clinic.
      Bariatric surgery is the most successful treatment for significant weight loss,
      resolution of type 2 diabetes and the prevention of future weight gain. Recent
      work with animal models has shed considerable light on the molecular
      underpinnings of the potent effects of these 'metabolic' surgical procedures.
      Here we review data from animal models and how these studies have evolved our
      understanding of the critical signalling systems that mediate the effects of
      bariatric surgery. These insights could lead to alternative therapies able to
      accomplish effects similar to bariatric surgery in a less invasive manner. 

PMID- 25374277
TI  - Increasing gene discovery and coverage using RNA-seq of globin RNA reduced
      porcine blood samples.
AB  - BACKGROUND: Transcriptome analysis of porcine whole blood has several
      applications, which include deciphering genetic mechanisms for host responses to
      viral infection and vaccination. The abundance of alpha- and beta-globin
      transcripts in blood, however, impedes the ability to cost-effectively detect
      transcripts of low abundance. Although protocols exist for reduction of globin
      transcripts from human and mouse/rat blood, preliminary work demonstrated these
      are not useful for porcine blood Globin Reduction (GR). Our objectives were to
      develop a porcine specific GR protocol and to evaluate the GR effects on gene
      discovery and sequence read coverage in RNA-sequencing (RNA-seq) experiments.
      RESULTS: A GR protocol for porcine blood samples was developed using RNase H with
      antisense oligonucleotides specifically targeting porcine hemoglobin alpha (HBA)
      and beta (HBB) mRNAs. Whole blood samples (n = 12) collected in Tempus tubes were
      used for evaluating the efficacy and effects of GR on RNA-seq. The HBA and HBB
      mRNA transcripts comprised an average of 46.1% of the mapped reads in pre-GR
      samples, but those reads reduced to an average of 8.9% in post-GR samples.
      Differential gene expression analysis showed that the expression level of 11,046
      genes were increased, whereas 34 genes, excluding HBA and HBB, showed decreased
      expression after GR (FDR <0.05). An additional 815 genes were detected only in
      post-GR samples. CONCLUSIONS: Our porcine specific GR primers and protocol
      minimize the number of reads of globin transcripts in whole blood samples and
      provides increased coverage as well as accuracy and reproducibility of
      transcriptome analysis. Increased detection of low abundance mRNAs will ensure
      that studies relying on transcriptome analyses do not miss information that may
      be vital to the success of the study.

PMID- 25374278
TI  - Controllable perovskite crystallization at a gas-solid interface for hole
      conductor-free solar cells with steady power conversion efficiency over 10%.
AB  - Depositing a pinhole-free perovskite film is of paramount importance to achieve
      high performance perovskite solar cells, especially in a heterojunction device
      format that is free of hole transport material (HTM). Here, we report that high
      quality pinhole-free CH3NH3PbI3 perovskite film can be controllably deposited via
      a facile low-temperature (<150  degrees C) gas-solid crystallization process. The
      crystallite formation process was compared with respect to the conventional
      solution approach, in which the needle-shaped solvation intermediates
      (CH3NH3PbI3.DMF and CH3NH3PbI3.H2O) have been recognized as the main cause for
      the incomplete coverage of the resultant film. By avoiding these intermediates,
      the films crystallized at the gas-solid interface offer several beneficial
      features for device performance including high surface coverage, small surface
      roughness, as well as controllable grain size. Highly efficient HTM-free
      perovskite solar cells were constructed with these pinhole-free CH3NH3PbI3 films,
      exhibiting significant enhancement of the light harvesting in the long wavelength
      regime with respect to the conventional solution processed one. Overall, the gas
      solid method yields devices with an impressive power conversion efficiency of
      10.6% with high reproducibility displaying a negligible deviation of 0.1% for a
      total of 30 cells. 

PMID- 25374280
TI  - Conditions for electronic reconstruction at stoichiometric polar/polar
      interfaces.
AB  - Relying on first principles simulations of ZnO(0 0 0 1)/MgO(1 1 1), MgO(1 1
      1)/CaO(1 1 1) and AlN(0 0 0 1)/GaN(0 0 0 1) interfaces and examples taken from
      the literature, we discuss under which conditions stoichiometric polar/polar
      interfaces may display an electronic reconstruction. We point out the role of the
      three contributions to the interfacial polarization discontinuity--structure,
      valence and electronic terms--of interfacial strains, and of finite size effects.
      Depending upon their relative values, the interfaces may be polar (compensated by
      an electron reconstruction), non-polar, or polar uncompensated at low thickness.
      We stress that, in superlattices or heterostructures made of thin layers, the
      prediction of the interface polarity character from the bulk properties of the
      two materials may be questionable.

PMID- 25374279
TI  - Inhibition of MDA-MB-231 breast cancer cell migration and invasion activity by
      andrographolide via suppression of nuclear factor-kappaB-dependent matrix
      metalloproteinase-9 expression.
AB  - Breast cancer is one of the most common types of cancer worldwide. The majority
      of patients with cancer succumb to the disease as a result of distant metastases
      (for example, in the bones), which cause severe complications. Despite
      advancements in breast cancer treatment, chemotherapeutic outcomes remain far
      from satisfactory, prompting a search for effective natural agents with few side
      effects. Andrographolide (AP), a natural diterpenoid lactone isolated from
      Andrographis paniculata, inhibits cancer cell growth. The current study aimed to
      examine the effect of AP on breast cancer cell proliferation, survival and
      progression in vitro and also its inhibitory activity on breast cancer bone
      metastasis in vivo. To achieve this, CCK8, flow cytometry, migration, invasion,
      western blot, PCR and luciferase reporter assay analyses were performed in vitro
      as well as establishing intratibial xenograft model of breast cancer bone
      metastasis in vivo. The results demonstrated that AP inhibits the migration and
      invasion of the MBA-MD-231 aggressive breast cancer cell line at non-lethal
      concentrations, in addition to suppressing proliferation and inducing apoptosis
      at high concentrations in vitro. In vivo, AP significantly inhibited the growth
      of tumors planted in bone and attenuated cancer-induced osteolysis. Tartrate
      resistant acid phosphatase staining revealed osteoclast activation in tumor
      bearing mice and AP was observed to attenuate this activation. The anti-tumor
      activity of AP in vitro and in vivo correlates with the downregulation of the
      nuclear factor kappaB signaling pathway and the inhibition of matrix
      metalloproteinase-9 expression levels. These results indicate that AP may be an
      effective anti-tumor agent for the treatment of breast cancer bone metastasis.

PMID- 25374281
TI  - Carcinoid tumors in children and adolescents: risk for second malignancies.
AB  - BACKGROUND: Carcinoid tumors (CTs) are rare in the pediatric population and are
      generally noted as an incidental finding on histopathologic examination. Cure is
      usually achieved with wide surgical excision. Second primary malignancies (SPM)
      of the gastrointestinal tract after CTs have been reported in 13% to 33% of
      affected adults. The risk of SPM appears highest after small bowel or appendiceal
      CTs and usually presents within 7 years from diagnosis. PURPOSE: The purpose of
      this study was to investigate the natural history of CTs in pediatric patients
      treated at a major children's hospital and to determine whether children and
      adolescents with primary CTs developed SPM during routine long-term follow-up.
      METHODS: We conducted a retrospective review of the medical records of children
      and adolescents with CTs diagnosed at Nationwide Children's Hospital, Columbus,
      Ohio between 1945 and 2012. RESULTS: Thirty-two patients with CT were identified,
      representing 0.48% of all malignancies diagnosed at Nationwide Children's
      Hospital. Mean age at presentation was 13 years (range, 8 to 20 y). The majority
      were appendiceal (87.5%) followed by bronchial (9.4%). Most of the appendiceal
      tumors presented with clinical appendicitis (25/28). Three had incidental
      appendectomies at the time of a planned abdominal surgery for other reasons. Four
      patients with appendiceal CTs had invasive features. All patients with
      appendiceal and bronchial CTs were successfully treated by complete surgical
      excision and were free of disease at an average of 7 years from diagnosis. None
      of our patients developed SPM during the period of observation (median 84 mo;
      range, 12 to 156 mo). CONCLUSIONS: In this single-institution retrospective
      review, survival of children with CT was excellent. No SPMs were observed over
      the period of follow-up differing from previously reported adult CT series.

PMID- 25374282
TI  - Simultaneous Adrenocortical Carcinoma and Neuroblastoma in an Infant With a Novel
      Germline p53 Mutation.
AB  - We present an infant with 2 simultaneous, but histologically distinct tumors with
      a novel germline p53 mutation. The child was found to have a paraspinal
      neuroblastoma, a concurrent adrenal cortical carcinoma, and an I162F p53 gene
      mutation. We review the associations of germline p53 mutations (or Li-Fraumeni
      syndrome) with both tumor types and the current research in similar germline p53
      mutations. Finally, we discuss the multiple ways in which our patient is unique
      including the paucity of cases with simultaneous but histologically unrelated
      tumors and the fact that our patient is the first reported case of an I162F
      germline p53 mutation. 

PMID- 25374283
TI  - Presentation and Long-term Outcome of High-grade Osteosarcoma: A Single
      institution Experience.
AB  - PURPOSE: To evaluate clinicopathologic characteristics, prognostic factors, and
      treatment outcome of pediatric/adolescent high-grade osteosarcoma patients.
      METHODS/PATIENTS: Retrospective evaluation of patients 21 years of age or younger
      with newly diagnosed high-grade osteosarcoma treated in a single institution.
      Effects of variables on event-free survival and overall survival (OS) were
      determined by using Kaplan-Meier survival analysis. Variables found to be
      significant were evaluated with multivariable Cox regression analysis. RESULTS:
      Seventy-seven patients diagnosed between January 1985 and December 2011 were
      included. Median follow-up time was 11.0 years (range, 1.6 to 26.4 y). Event-free
      survival at 5 and 10 years was 38%+/-11% and 38%+/-11%, respectively. OS at 5 and
      10 years was 51%+/-12% and 45%+/-12%, respectively. Metastatic disease, prolonged
      time interval to resumption of chemotherapy, lower tumor necrosis rate, and lack
      of achievement of complete response at the end of first-line chemotherapy
      treatment were associated with inferior OS probabilities in univariate analysis.
      Upon multivariate analysis, only achievement of complete response at the end of
      first-line chemotherapy and tumor necrosis rate retained independent prognostic
      significance. CONCLUSIONS: Prognostic factors and long-term survival are similar
      to those previously described. Reduction of global time interval to resumption of
      chemotherapy as well as a more specific and validated definition of pulmonary
      metastases at diagnosis are needed.

PMID- 25374284
TI  - Steroid-responsive anemia in patients of Ghosal hematodiaphyseal dysplasia:
      simple to diagnose and easy to treat.
AB  - Ghosal hematodiaphyseal dysplasia (GHDD) is a recently recognized cause of
      steroid-responsive anemia. We would like to report 3 cases of GHDD who presented
      in early childhood with moderate to severe anemia, splenomegaly, and a
      hypocellular marrow with increased reticulin. They were easily diagnosed with
      long-bone x-rays showing diaphyseal and metaphyseal widening and loss of
      diaphyseal constriction. All cases dramatically responded to oral steroid and no
      longer needed blood transfusion. They required steroid at low doses for long term
      (up to 5 y). GHDD is easy to diagnose with long-bone radiography and consistently
      responds to steroid. It should therefore be considered as a differential
      diagnosis of unusual anemia in early childhood, especially in children from the
      Middle East or the Indian subcontinent. 

PMID- 25374285
TI  - Nonhematologic toxicity of imatinib mesylate in pediatric patients with chronic
      myelogenous leukemia: a predominance of musculoskeletal pain.
AB  - Therapy with the tyrosine kinase inhibitor imatinib mesylate has become standard
      initial treatment for adult and pediatric patients with chronic myelogenous
      leukemia. Long-term follow-up data are now available in the adult population, and
      the toxicity profile of imatinib mesylate among adults has been extensively
      studied and reported. Despite its increasing use in the pediatric population,
      there are limited data regarding adverse event profiles of imatinib mesylate in
      children, and few reports exist in the literature focusing on nonhematologic
      toxicity in this population. We reviewed our institutional experience with
      imatinib therapy for chronic myelogenous leukemia over an 8-year period of time.
      Nine pediatric patients began therapy with imatinib mesylate and were included in
      this review. We reviewed the occurrence of nonhematologic toxicity in this cohort
      and the impact of that toxicity on continuation of therapy. Eight patients
      experienced nonhematologic toxicity, including nausea/vomiting (44.4%) and
      musculoskeletal pain (88.9%). Three patients (33.3%) required discontinuation of
      imatinib therapy due to grade 3/4 musculoskeletal pain, a rate that is
      significantly higher than that seen in the adult population. As imatinib therapy
      becomes increasingly widespread in the treatment of pediatric malignancies, there
      may be different patterns of clinically significant nonhematologic toxicity,
      including higher grade musculoskeletal pain. 

PMID- 25374286
TI  - Successful T-cell-depleted haploidentical hematopoietic stem cell transplantation
      in a child with dyskeratosis congenita after a fludarabine-based conditioning
      regimen.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure for
      marrow failure associated with dyskeratosis congenita (DC). Data on transplants
      from alternative donors are limited. We describe a boy with DC and severe
      aplastic anemia who underwent haploidentical T-cell depleted HSCT using a reduced
      intensity conditioning regimen. He underwent engraftment without toxicity or
      GVHD. His posttransplant course was complicated by EBV reactivation, treated with
      rituximab and EBV-specific T lymphocytes. After 26 months, he is in complete
      chimerism, with normal blood count and no sign of GVHD or pulmonary dysfunction.
      To the best of our knowledge, this is the first report of DC successfully treated
      with allogeneic HSCT from a haploidentical family donor. 

PMID- 25374287
TI  - Safety and Outcomes of Extracorporeal Photopheresis With the Therakos Cellex
      System for Graft-Versus-Host Disease in Pediatric Patients.
AB  - Extracorporeal photopheresis (ECP) is a difficult procedure to perform in the
      pediatric population. This is a retrospective review of 12 pediatric patients who
      underwent photopheresis with the Therakos Cellex system for graft-versus-host
      disease (GVHD). Acute GVHD (aGVHD) occurred in 6 patients, and overlap syndrome
      and chronic GVHD (cGVHD) occurred in 4 and 2 patients, respectively. The ECP
      regimen was the same for all aGVHD and cGVHD patients: initially, every week (2
      sessions/wk) for 2 months; next, every 2 weeks for 2 months; and finally, every
      month for at least 1 year. Improvement was observed in 7 of 10 aGVHD patients
      (70%) and in 4 of 6 cGVHD patients (66%). Eleven patients had skin involvement
      before ECP; 9 of them responded to treatment (81%). Gastrointestinal involvement
      occurred in 8 patients; 5 of them experienced improvement during ECP treatment
      (62%). All 4 patients with liver involvement failed to respond. No serious
      adverse reactions occurred. In conclusion, our study demonstrates that ECP with
      the Therakos Cellex system is a safe treatment option for GVHD in children,
      allowing the tapering of immunosuppressants by at least half. 

PMID- 25374288
TI  - Maternal depressive symptoms and parenting practices 3-months postpartum.
AB  - Using data from two postpartum depression randomized trials, we examined the
      association between postpartum depressive symptoms and parenting practices among
      a diverse group of mothers. We examined the association between safety practices
      (back sleep position, car seat use, smoke alarm), feeding practices
      (breastfeeding, infant intake of cereal, juice, water), and health care practices
      (routine well child and Emergency Room (ER) visits) with 3-month postpartum
      depressive symptoms assessed using the Edinburgh Depression Scale (EPDS >=10).
      Fifty-one percent of mothers were black or Latina, 33 % had Medicaid, and 30 %
      were foreign born. Depressed mothers were less likely to have their infant use
      back sleep position (60 vs. 79 %, p < .001), always use a car seat (67 vs. 84 %,
      p < .001), more likely to feed their infants water, juice, or cereal (36 vs. 25
      %, p = .04 respectively), and to bring their babies for ER visits (26 vs. 16 %, p
      = .03) as compared with non-depressed mothers. In multivariable model, depressed
      mothers remained less likely to have their infant use the back sleep position, to
      use a car seat, and to have a working smoke alarm in the home. Findings suggest
      the need to intervene early among mothers with depressive symptoms and reinforce
      positive parenting practices.

PMID- 25374289
TI  - Managing patients with ulcerative colitis with infliximab in primary and referral
      gastroenterology centers: similarities and differences.

PMID- 25374290
TI  - Comment on an optimized patient-reported ulcerative colitis disease activity
      measure derived from the mayo score and the simple clinical colitis activity
      index.

PMID- 25374291
TI  - A robust and modular synthesis of ynamides.
AB  - A flexible, modular ynamide synthesis is reported that uses trichloroethene as an
      inexpensive two carbon synthon. A wide range of amides and electrophiles can be
      converted to the corresponding ynamides, importantly including acyclic
      carbamates, hindered amides, and aryl amides. This method thus overcomes many of
      the limitations of other approaches to this useful functionality. 

PMID- 25374292
TI  - Authors' reply to Gandjour: "Are current cost-effectiveness thresholds for low-
      and middle-income countries useful? Examples from the world of vaccines".

PMID- 25374293
TI  - Biomarkers as point-of-care tests to guide prescription of  antibiotics in
      patients with acute respiratory infections in  primary care.
AB  - Background Acute respiratory infections (ARIs) are by far the most common reason
      for prescribing an antibiotic in primary care, even though the majority of ARIs
      are of viral or non-severe bacterial aetiology. Unnecessary antibiotic use will,
      in many cases, not be beneficial to the patients' recovery and expose them to
      potential side effects. Furthermore, as a causal link exists between antibiotic
      use and antibiotic resistance, reducing unnecessary antibiotic use is a key
      factor in controlling this important problem. Antibiotic resistance puts
      increasing burdens on healthcare services and renders patients at risk of future
      ineffective treatments, in turn increasing morbidity and mortality from
      infectious diseases. One strategy aiming to reduce antibiotic use in primary care
      is the guidance of antibiotic treatment by use of a point-of-care biomarker. A
      point-of-care biomarker of infection forms part of the acute phase response to
      acute tissue injury regardless of the aetiology (infection, trauma and
      inflammation) and may in the correct clinical context be used as a surrogate
      marker of infection,possibly assisting the doctor in the clinical management of
      ARIs.Objectives To assess the benefits and harms of point-of-care biomarker tests
      of infection to guide antibiotic treatment in patients presenting with symptoms
      of acute respiratory infections in primary care settings regardless of age.Search
      methods We searched CENTRAL (2013, Issue 12), MEDLINE (1946 to January 2014),
      EMBASE (2010 to January 2014), CINAHL (1981 to January 2014), Web of Science
      (1955 to January 2014) and LILACS (1982 to January 2014).Selection criteria We
      included randomised controlled trials (RCTs) in primary care patients with ARIs
      that compared use of point-of-care biomarkers with standard of care. We included
      trials that randomised individual patients as well as trials that randomised
      clusters of patients(cluster-RCTs).Two review authors independently extracted
      data on the following outcomes: i) impact on antibiotic use; ii) duration of and
      recovery from infection; iii) complications including the number of re
      consultations, hospitalisations and mortality; iv) patient satisfaction. We
      assessed the risk of bias of all included trials and applied GRADE. We used
      random-effects meta-analyses when feasible. We further analysed results with a
      high level of heterogeneity in pre-specified subgroups of individually and
      cluster-RCTs.Main results The only point-of-care biomarker of infection currently
      available to primary care identified in this review was C-reactive protein. We
      included six trials (3284 participants; 139 children) that evaluated a C-reactive
      protein point-of-care test. The available information was from trials with a low
      to moderate risk of bias that address the main objectives of this review.Overall
      a reduction in the use of antibiotic treatments was found in the C-reactive
      protein group (631/1685) versus standard of care(785/1599). However, the high
      level of heterogeneity and the statistically significant test for subgroup
      differences between the three RCTs and three cluster-RCTs suggest that the
      results of the meta-analysis on antibiotic use should be interpreted with caution
      and the pooled effect estimate (risk ratio (RR) 0.78, 95% confidence interval
      (CI) 0.66 to 0.92; I2 statistic = 68%) may not be meaningful.The observed
      heterogeneity disappeared in our pre planned subgroup analysis based on study
      design: RR 0.90, 95% CI 0.80 to 1.02; I2 statistic = 5% for RCTs and RR 0.68, 95%
      CI 0.61 to 0.75; I2 statistic = 0% for cluster-RCTs, suggesting that this was the
      cause of the observed heterogeneity.There was no difference between using a C
      reactive protein point-of-care test and standard care in clinical recovery
      (defined as at least substantial improvement at day 7 and 28 or need for re
      consultations day 28). However, we noted an increase in hospitalisations in the C
      reactive protein group in one study, but this was based on few events and may be
      a chance finding. No deaths were reported in any of the included studies.We
      classified the quality of the evidence as moderate according to GRADE due to
      imprecision of the main effect estimate.Authors' conclusions A point-of-care
      biomarker (e.g. C-reactive protein) to guide antibiotic treatment of ARIs in
      primary care can reduce antibiotic use,although the degree of reduction remains
      uncertain. Used as an adjunct to a doctor's clinical examination this reduction
      in antibiotic use did not affect patient-reported outcomes, including recovery
      from and duration of illness.However, a possible increase in hospitalisations is
      of concern. A more precise effect estimate is needed to assess the costs of the
      intervention and compare the use of a point-of-care biomarker to other antibiotic
      saving strategies.

PMID- 25374294
TI  - The Relationship between Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1
      Ligands Containing Apolipoprotein B and the Cardio-Ankle Vascular Index in
      Healthy Community Inhabitants: The KOBE Study.
AB  - AIMS: Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 ligands
      containing apolipoprotein B (LAB) and lectin-like oxidized LDL receptor-1 (LOX-1)
      are known as LOX-1-related modified LDL indicators. These indicators play an
      important role in the early phase atherosclerosis, but the relationship between
      these indicators and subclinical atherosclerosis, as represented by the cardio
      ankle vascular index (CAVI), has not been assessed. We herein investigated the
      association of LOX-1- related modified LDL indicators and the CAVI in healthy,
      Japanese urban community inhabitants who were considered to be at low risk for
      cardiovascular disease (CVD). METHODS: The participants were 515 healthy Japanese
      (310 men and 205 women) without a history of CVD, cancer or the use of medication
      for hypertension, diabetes or dyslipidaemia. To estimate the association between
      LOX-1-related modified LDL indicators (LAB, soluble form of LOX-1 (sLOX-1)) and
      the CAVI, we performed multivariable linear regression analyses with possible
      confounders such as the serum LDL cholesterol level. RESULTS: The plasma LAB
      showed a positive association with the CAVI in men (standardized coefficient:
      0.11, p = 0.04). This relationship was not observed in women. On the other hand,
      no clear association was observed between the CAVI and the plasma sLOX-1 level in
      either sex. CONCLUSIONS: The plasma LAB levels may represent a useful marker for
      detecting potential atherosclerosis in healthy individuals considered to be at
      low risk for atherosclerosis and CVD. Further studies are needed to confirm the
      present findings.

PMID- 25374296
TI  - Mixed non-covalent assemblies of ethynyl nile red and ethynyl pyrene along
      oligonucleotide templates.
AB  - Ethynyl pyrene and ethynyl nile red as modifications at the 5-position of 2'
      deoxyuridines self-assemble non-covalently and specifically along oligo-2'
      deoxyadenosines as templates. Oligo-2'-deoxyadenosines of the lengths (dA)10
      (dA)20 are able to retain nearly exactly as many ethynyl nile red units in
      solution as binding sites are available on these templates. In contrast, in the
      presence of oligo-2'-thymidines the ethynyl nile red moieties are similarly
      insoluble to those in the absence of any oligonucleotide and yield an aggregate.
      The mixed assemblies of both chromophores are highly ordered, show left-handed
      chirality and yield dual fluorescence. The strong excitonic coupling indicates
      assemblies with a high degree of order. These results show that DNA represents an
      important supramolecular scaffold for the templated, helical and non-covalent
      arrangement not only for one type of chromophore but also for mixtures of two
      different chromophores. 

PMID- 25374298
TI  - Double ureteral access sheath (UAS) technique for complicated distal ureteral
      stone.

PMID- 25374299
TI  - Atypical teratoid rhabdoid tumour of the spine: report of a case and literature
      review.
AB  - Atypical teratoid rhabdoid tumour (ATRT) is a rare and highly aggressive
      malignant neoplasm of the central nervous system (CNS), which occurs
      predominantly in children less than 2 years of age. There are less than 50 cases
      described in adult. We report a case of primary spinal ATRT in a 65-year-old male
      who presented to us with cauda equina syndrome. To the best of our knowledge, our
      patient is the (1) second oldest patient to be diagnosed with ATRT and only the
      third case of adult spinal ATRT report in the literature; (2) first reported case
      of CNS ATRT occurring in a patient with non-rhabdoid renal cancer; (3) first
      adult patient of ATRT to present with cauda equina syndrome. 

PMID- 25374297
TI  - Bacterial chemoreceptors and chemoeffectors.
AB  - Bacteria use chemotaxis signaling pathways to sense environmental changes.
      Escherichia coli chemotaxis system represents an ideal model that illustrates
      fundamental principles of biological signaling processes. Chemoreceptors are
      crucial signaling proteins that mediate taxis toward a wide range of
      chemoeffectors. Recently, in deep study of the biochemical and structural
      features of chemoreceptors, the organization of higher-order clusters in native
      cells, and the signal transduction mechanisms related to the on-off signal output
      provides us with general insights to understand how chemotaxis performs high
      sensitivity, precise adaptation, signal amplification, and wide dynamic range.
      Along with the increasing knowledge, bacterial chemoreceptors can be engineered
      to sense novel chemoeffectors, which has extensive applications in therapeutics
      and industry. Here we mainly review recent advances in the E. coli chemotaxis
      system involving structure and organization of chemoreceptors, discovery, design,
      and characterization of chemoeffectors, and signal recognition and transduction
      mechanisms. Possible strategies for changing the specificity of bacterial
      chemoreceptors to sense novel chemoeffectors are also discussed. 

PMID- 25374300
TI  - Relationship between sagittal spinal alignment and the incidence of vertebral
      fracture in menopausal women with osteoporosis: a multicenter longitudinal follow
      up study.
AB  - PURPOSE: To investigate the relationship between sagittal spinal alignment and
      the incidence of vertebral fracture in patients with osteoporosis. METHODS: A
      cohort of 1,044 postmenopausal women with osteoporosis were prospectively
      observed for the incidence of lumbar vertebral fracture. Baseline characteristics
      of the subjects were recorded, including age, year post-menopause, body height
      and weight, lumbar spine BMD (LSBMD) and femoral neck BMD (FNBMD). Patients with
      radiologically diagnosed lumbar vertebral fractures were assigned to the fracture
      group, and 150 randomly selected participants were assigned to the non-fracture
      group. Parameters depicting sagittal spinal alignment, including sacral slope
      (SS), pelvic tilt, pelvic incidence (PI), thoracic kyphpsis, lumbar lordosis
      (LL), lumbar lordosis index (LLI) and sagittal vertical axis, were measured for
      both groups. Comparison between the two groups was carried out by Student's t
      test. Variables showing significant differences were entered into a logistic
      regression analysis to determine the independent risk factors. RESULTS: Patients
      with fracture events had significantly lower LSBMD as well as a significantly
      longer year post-menopause. Besides, patients with vertebral fracture were found
      to have significantly lower LL, LLI, SS and PI. Regression analysis showed that
      LSBMD (OR = 0.27), LL (OR = 0.3), LLI (OR = 0.43) and PI (OR = 0.67) had
      significant associations with the risk of vertebral fracture. CONCLUSIONS:
      Osteoporosis patients with low LL, LLI, and PI could be at high risk of lumbar
      vertebral fracture. In addition to BMD, the abnormal sagittal spinal profile
      should also be taken into consideration when predicting the incidence of
      vertebral fracture in such patients.

PMID- 25374301
TI  - Adolescent idiopathic scoliosis: 70% agreement in expert opinion?

PMID- 25374302
TI  - Molecular characterization of Babesia and Cytauxzoon species in wild South
      African meerkats.
AB  - Piroplasms, including Babesia, Cytauxzoon and Theileria species, frequently
      infect domestic and wild mammals. At present, there is no information on the
      occurrence and molecular identity of these tick-borne blood parasites in the
      meerkat, one of South Africa's most endearing wildlife celebrities. Meerkats live
      in territorial groups, which may occur on ranchland in close proximity to humans,
      pets and livestock. Blood collected from 46 healthy meerkats living in the South
      African Kalahari desert was screened by microscopy and molecular methods, using
      PCR and DNA sequencing of 18S rRNA and ITS1 genes. We found that meerkats were
      infected by 2 species: one species related to Babesia sp. and one species related
      to Cytauxzoon sp. Ninety one percent of the meerkats were infected by the
      Cytauxzoon and/or the Babesia species. Co-infection occurred in 46% of meerkats.
      The pathogenicity and vectors of these two piroplasm species remains to be
      determined. 

PMID- 25374303
TI  - Magnetic resonance imaging of post-ischemic blood-brain barrier damage with
      PEGylated iron oxide nanoparticles.
AB  - Blood-brain barrier (BBB) damage during ischemia may induce devastating
      consequences like cerebral edema and hemorrhagic transformation. This study
      presents a novel strategy for dynamically imaging of BBB damage with PEGylated
      supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The
      employment of SPIONs as contrast agents made it possible to dynamically image the
      BBB permeability alterations and ischemic lesions simultaneously with T2-weighted
      MRI, and the monitoring could last up to 24 h with a single administration of
      PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB
      damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd
      DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The
      immunohistochemical staining also confirmed the leakage of SPION-PEG from
      cerebral vessels into parenchyma. This study provides a novel and convenient
      route for imaging BBB alteration in the experimental ischemic stroke model. 

PMID- 25374304
TI  - ROS1 gene rearrangement and copy number gain in non-small cell lung cancer.
AB  - ROS1 has attracted much attention as a possible oncogenic driver and ROS1
      rearranged tumors show sensitivity to most ALK inhibitors. We aimed to clarify
      the prevalence of ROS1 gene rearrangement and investigate the clinical
      implications of ROS1 gene copy number gain (CNG) in non-small cell lung cancer
      (NSCLC) patients. We carried out fluorescent in situ hybridization with ROS1 and
      centromere enumeration 6 probes and immunohistochemistry for ROS1 protein
      expression. ROS1 rearrangement was detected in 3 of 375 samples (0.8 %); all of
      whom were female, never-smokers, and harbored an adenocarcinoma component. ROS1
      gene CNG was found in 18 cases (4.8 %). ROS1 gene CNG was significantly
      associated with shorter disease-free survival (DFS, 12 vs. 58 months; p = 0.003)
      and shorter overall survival (OS, 40 vs. 67 months; p <0.001) than the group
      without CNG. Multivariate analysis confirmed that ROS1 gene CNG was significantly
      associated with poorer DFS (hazard ratio [HR]=2.16, 95 % confidence interval [CI]
      = 1.22-3.81, p = 0.008), and OS ([HR] = 2.53, 95 % [CI] = 1.31-4.89, p = 0.006).
      ROS1 protein overexpression was observed in 5.0 % (18 out of 357), of which 2
      cases harbored ROS1 gene rearrangement. There was no statistically significant
      correlation between ROS1 gene CNG and protein overexpression. This study
      demonstrated ROS1 gene rearrangement was detected in 0.8 % of surgically resected
      NSCLC; and ROS1 gene CNG is an independent poor prognostic factor. This survival
      analyses may contribute to future studies on the utility of ROS1-targeted therapy
      for patients.

PMID- 25374305
TI  - STAT3 as a possible therapeutic target in human malignancies: lessons from acute
      myeloid leukemia.
AB  - STAT3 is important for transcriptional regulation in human acute myeloid leukemia
      (AML). STAT3 has thousands of potential DNA binding sites but usually shows cell
      type specific binding preferences to a limited number of these. Furthermore, AML
      is a very heterogeneous disease, and studies of the prognostic impact of STAT3 in
      human AML have also given conflicting results. A more detailed characterization
      of STAT3 functions and the expression of various isoforms in human AML will
      therefore be required before it is possible to design clinical studies of STAT3
      inhibitors in this disease, and it will be especially important to investigate
      whether the functions of STAT3 differ between patients. Several other
      malignancies also show extensive biological heterogeneity, and the present
      discussion and the suggested scientific approaches may thus be relevant for other
      cancer patients. 

PMID- 25374306
TI  - Hinge-like structure induced unusual properties of black phosphorus and new
      strategies to improve the thermoelectric performance.
AB  - We systematically investigated the geometric, electronic and thermoelectric (TE)
      properties of bulk black phosphorus (BP) under strain. The hinge-like structure
      of BP brings unusual mechanical responses such as anisotropic Young's modulus and
      negative Poisson's ratio. A sensitive electronic structure of BP makes it
      transform among metal, direct and indirect semiconductors under strain. The
      maximal figure of merit ZT of BP is found to be 0.72 at 800 K that could be
      enhanced to 0.87 by exerting an appropriate strain, revealing BP could be a
      potential medium-high temperature TE material. Such strain-induced enhancements
      of TE performance are often observed to occur at the boundary of the direct
      indirect band gap transition, which can be attributed to the increase of
      degeneracy of energy valleys at the transition point. By comparing the structure
      of BP with SnSe, a family of potential TE materials with hinge-like structure are
      suggested. This study not only exposes various novel properties of BP under
      strain, but also proposes effective strategies to seek for better TE materials. 

PMID- 25374307
TI  - Composite mantle cell and primary cutaneous anaplastic large cell lymphoma: case
      report and review of the literature.
AB  - We describe the first reported occurrence of a composite cutaneous lymphoma
      involving a mantle cell lymphoma (MCL) and primary cutaneous anaplastic large
      cell lymphoma. The lesion occurred in a 76-year-old man with longstanding MCL who
      developed nodular skin lesions on his trunk and extremities. Biopsy revealed a
      CD30-positive lymphoma with pathological features characteristic of cutaneous
      anaplastic large cell lymphoma in the superficial dermis and a subjacent deposit
      of MCL in the deep dermis and subcutaneous adipose tissue. Immunophenotyping
      demonstrated T versus B lymphoid origin, respectively, for the 2 neoplasms, and
      fluorescence in situ hybridization demonstrated an 11;14 chromosomal
      translocation exclusively in the MCL. These results argue that the lymphomas
      represented clonally distinct neoplasms. Our case illustrates the extreme
      diversity associated with the cutaneous manifestations of lymphoid neoplasia and
      in particular of composite lymphomas, which present diagnostic challenges for
      clinicians and pathologists alike.

PMID- 25374308
TI  - Effect of induced electric field on migration of a charged porous particle.
AB  - The effect of ambient fluid flow on a charged porous spherical particle suspended
      in an aqueous medium is analyzed. The porous particle is ion permeable and fluid
      penetrable. The induced electric field due to the polarization of the particle's
      electric double layer and counterion condensation leads to a hindrance effect on
      particle migration by producing an electric force. The influence of this
      retardation force on the hydrodynamics of the particle is studied through the
      Nernst-Planck equations, which are coupled with the Stokes-Brinkman equation. The
      interactions of the double-layer polarization, shielding effect, electroosmosis
      of unbalanced ions and fluid convection are analyzed. The settling velocity and
      fluid collection efficiency of the charged aggregate is determined. We have
      studied the electrokinetics for a wide range of fixed charge density and
      permeability of the particle with no assumption made on the thickness of the
      double layer relative to the dimension of the particle. 

PMID- 25374309
TI  - Static versus dynamic analysis of the influence of gravity on concentration non
      equilibrium fluctuations.
AB  - In a binary fluid mixture subject to gravity and a stabilizing concentration
      gradient, concentration non-equilibrium fluctuations are long-ranged. While the
      gradient leads to an enhancement of the respective equilibrium fluctuations, the
      effect of gravity is a damping of fluctuations larger than a "characteristic"
      size. This damping is visible both in the fluctuation power spectrum probed by
      static and the temporal correlation function probed by dynamic light scattering.
      One aspect of the "characteristic" size can be appreciated by the dynamic
      analysis; in fact at the corresponding "characteristic" wave vector q* one can
      observe a maximum of the fluctuation time constant indicating the more persistent
      fluctuation of the system. Also in the static analysis a "characteristic" size
      can be extracted from the crossover wave vector. According to common theoretical
      concepts, the result should be the same in both cases. In the present work we
      provide evidence for a systematic difference in the experimentally observed
      "characteristic" size as obtained by static and dynamic measurements. Our
      observation thus points out the need for a more refined theory of non-equilibrium
      concentration fluctuations.

PMID- 25374310
TI  - Social stressors and air pollution across New York City communities: a spatial
      approach for assessing correlations among multiple exposures.
AB  - BACKGROUND: Recent toxicological and epidemiological evidence suggests that
      chronic psychosocial stress may modify pollution effects on health. Thus, there
      is increasing interest in refined methods for assessing and incorporating non
      chemical exposures, including social stressors, into environmental health
      research, towards identifying whether and how psychosocial stress interacts with
      chemical exposures to influence health and health disparities. We present a
      flexible, GIS-based approach for examining spatial patterns within and among a
      range of social stressors, and their spatial relationships with air pollution,
      across New York City, towards understanding their combined effects on health.
      METHODS: We identified a wide suite of administrative indicators of community
      level social stressors (2008-2010), and applied simultaneous autoregressive
      models and factor analysis to characterize spatial correlations among social
      stressors, and between social stressors and air pollutants, using New York City
      Community Air Survey (NYCCAS) data (2008-2009). Finally, we provide an
      exploratory ecologic analysis evaluating possible modification of the
      relationship between nitrogen dioxide (NO2) and childhood asthma Emergency
      Department (ED) visit rates by social stressors, to demonstrate how the methods
      used to assess stressor exposure (and/or consequent psychosocial stress) may
      alter model results. RESULTS: Administrative indicators of a range of social
      stressors (e.g., high crime rate, residential crowding rate) were not
      consistently correlated (rho = - 0.44 to 0.89), nor were they consistently
      correlated with indicators of socioeconomic position (rho = - 0.54 to 0.89).
      Factor analysis using 26 stressor indicators suggested geographically distinct
      patterns of social stressors, characterized by three factors: violent crime and
      physical disorder, crowding and poor access to resources, and noise disruption
      and property crimes. In an exploratory ecologic analysis, these factors were
      differentially associated with area-average NO2 and childhood asthma ED visits.
      For example, only the 'violent crime and disorder' factor was significantly
      associated with asthma ED visits, and only the 'crowding and resource access'
      factor modified the association between area-level NO2 and asthma ED visits.
      CONCLUSIONS: This spatial approach enabled quantification of complex spatial
      patterning and confounding between chemical and non-chemical exposures, and can
      inform study design for epidemiological studies of separate and combined effects
      of multiple urban exposures.

PMID- 25374311
TI  - Associations between serum uric acid levels and the incidence of hypertension and
      metabolic syndrome: a 4-year follow-up study of a large screened cohort in
      Okinawa, Japan.
AB  - The purpose of this study was to examine the associations between serum uric acid
      (SUA) levels and the incidences of hypertension and metabolic syndrome (MetS) in
      a large screened cohort of Japanese men and women. We evaluated 4812 subjects
      (males, 2528; females, 2284; mean age, 47.5 years) who underwent health checkups
      between 2006 and 2010 and were free of hypertension and MetS in 2006. After 4
      years, 618 (13%), 764 (16%) and 158 (3%) subjects developed hypertension, MetS
      and hypertension with MetS, respectively. Increased SUA levels were significantly
      and positively associated with the incidences of hypertension, MetS and
      hypertension with MetS. Compared with the first quartile of SUA levels, the odds
      ratios (95% confidence intervals) for the third and fourth quartiles,
      respectively, were as follows: 1.5 (1.1-2.1; P = 0.0128) and 1.8 (1.2-2.5; P =
      0.0022) for hypertension, 1.3 (0.9-1.9; P = 0.1910) and 1.8 (1.2-2.7; P = 0.0039)
      for MetS and 2.7 (1.1-6.6; P = 0.0276) and 3.2 (1.3-8.0; P = 0.0115) for
      hypertension with MetS. In conclusion, increased SUA levels were significantly
      and independently associated with the incidences of hypertension and MetS in
      subjects without hypertension or MetS at baseline. Increased SUA levels might
      also be correlated with the incidence of hypertension with MetS.

PMID- 25374312
TI  - Right ventricular free wall dyskinesis in the setting of left ventricular non
      compaction: a case report.
AB  - BACKGROUND: Left ventricular non compaction is a relatively rare congenital
      disorder characterized by prominent trabeculations and intertrabecular recesses
      with the potential for thromboembolism, arrhythmias, and sudden cardiac death as
      adverse effects. Echocardiography has traditionally been employed as the primary
      mode of imaging; however, with the advent of cardiac magnetic resonance as a more
      precise imaging technique, the disorder known as left ventricle non compaction is
      becoming more broadly defined with increasing recognition of right ventricle (RV)
      involvement. CASE PRESENTATION: This report describes a 52-year-old Caucasian
      female with new onset atrial fibrillation with an unusual finding of left
      ventricular non compaction and right ventricular dysfunction on transthoracic
      echocardiogram with preserved left ventricular ejection fraction. Cardiac
      magnetic resonance imaging demonstrated a disproportionately affected right
      ventricle, with apical free wall dyskinesis. CONCLUSIONS: This case illustrates
      the unique occurrence of left ventricular non compaction with preserved ejection
      fraction alongside RV free wall dyskinesis and RV systolic dysfunction. The
      significance of this is yet unknown given the paucity of existing literature.
      This report serves to highlight the vast heterogeneity within left ventricular
      non compaction as we are better able to delineate this disorder using
      increasingly sophisticated imaging techniques.

PMID- 25374314
TI  - Preparing effective experimental data for pharmaceutical patent applications from
      US and Japanese perspectives.

PMID- 25374313
TI  - Community health worker interventions for Latinos with type 2 diabetes: a
      systematic review of randomized controlled trials.
AB  - This systematic review aimed to synthesize glucose (HbA1c) outcomes of community
      health worker (CHW)-delivered interventions for Latinos with type 2 diabetes that
      were tested in randomized controlled trials and to summarize characteristics of
      the targeted populations and interventions, including the background, training,
      and supervision of the CHWs. Searches of PubMed and Google Scholar databases and
      references from selected articles identified 12 studies that met the inclusion
      criteria. Of these, seven reported statistically significant improvements in
      HbA1c. Study participants were largely low-income, female, and Spanish-speaking
      and had uncontrolled diabetes. The CHWs led the interventions alone, in pairs, or
      as part of a team. Interventions varied considerably in session time, duration,
      and number. Most met standards for tailored, high-intensity interventions and
      half were theory-based. Overall, methodological quality was good but there were
      inconsistencies in the reporting of key information. Future research should
      report in greater detail CHW background, training, and supervision; examine
      factors associated with intervention effectiveness; and provide data on cost and
      cost-effectiveness.

PMID- 25374315
TI  - Intellectual property strategy for regenerative medicine: is it time to
      'regenerate'?

PMID- 25374316
TI  - What are the risks of second medical use and dosing regimens in pharmaceutical
      patenting?

PMID- 25374318
TI  - The extraterritoriality of US patents on the pharmaceutical industry.
AB  - As pharmaceutical industries have rapidly modernized and globalized, borders have
      been blurred and multiple entities in different countries are now involved with
      the manufacture, supply, distribution, dispensing and administration of even a
      single drug in the pharmaceutical industry. The cross jurisdictional nature of
      the modern pharmaceutical industry presents new challenges to limitations on the
      extraterritorial reach of US patents. The enforcement of US patents outside the
      jurisdictional boundaries of the USA has judicially evolved through cases such as
      Deep South, Microsoft, Bayer AG, Union Carbide, AT&T, Cardiac Pacemakers and
      others. This article explores the effects of recent cases on the extraterritorial
      enforcement of US pharmaceutical patents, particularly when different types of
      claims are involved. 

PMID- 25374319
TI  - Patent owner options for correcting errors in US patents after grant.
AB  - With the implementation of the America Invents Act, there has been considerable
      focus on options for third parties to attack the validity of US patents. However,
      there have also been a number of important court cases in the USA that have
      considered the question of what may be patented in the USA. These decisions have
      radically changed what may be patented in the USA, particularly in the field of
      biopharmaceuticals. Equally important to understanding what options are available
      to a third party to attack a patent, are the options and procedures available to
      patent owners to correct errors in patents and strengthen the validity of a
      patent prior to enforcement. 

PMID- 25374320
TI  - Inhibitors of voltage-gated sodium channel Nav1.7: patent applications since
      2010.
AB  - There has been intense interest in developing inhibitors of the sodium channel
      Nav1.7 because genetic studies have established very strong validation for the
      efficacy to alleviate both inflammatory and neuropathic pain. This review
      summarizes patent applications targeting Nav1.7 since 2010 until May, 2014. We
      have classified the patents into three categories as follows: small molecules
      with well-defined molecular selectivity among sodium channel isoforms;
      biologicals with well-defined molecular selectivity; and, small molecules that
      inhibit Nav1.7 with unknown molecular selectivity. Most of the review is
      dedicated to small molecule selective compounds. 

PMID- 25374321
TI  - New spleen tyrosine kinase inhibitors: patent applications published during 2011
      2013.
AB  - Spleen tyrosine kinase (SYK) is one of the more advanced small-molecule targets
      with regard to clinical development for treatment of inflammatory diseases. In
      this review we continue our analysis of the patent literature covering the time
      period 2011-2013. The analysis relates to any organization that has filed
      applications that explicitly discloses SYK as the intended target. In the last 2
      years there has been a surge of application with a few new entries in a crowded
      field with the structural theme of compounds in these applications being a
      traditional type I ATP competitive inhibitor [ 1 ]. This overview of the SYK
      patent literature and the learning's of the inhibitors substitution patterns
      would be an important reading for anyone working in the area of SYK inhibitors. 

PMID- 25374322
TI  - Fluorescent probes for biomedical applications (2009-2014).
AB  - The discovery and subsequent development of fluorescent probes was one of the
      most exciting innovations in life sciences, which marked the beginning of
      interpretation of numerous biological phenomena. Today, fluorescent probes are
      used for a wide range of biomedical applications, such as pharmaceutical
      research, clinical diagnostics and high-throughput screening, to name a few.
      Despite the availability of a large number of these probes, efforts to invent
      newer versions utilizing novel chemistry to address limitations of the current
      approaches continue. This review article gives a rundown on 'small-molecule
      fluorescent probes' patents/patent applications from January 2009 to March 2014.
      The patent literature was classified based on 'preparation' and 'biomedical
      applications' of these 'fluorescing wonders'. 

PMID- 25374323
TI  - Inhibitory activities of selected Kampo formulations on human aldose reductase.
AB  - BACKGROUND: Diabetes complications include various symptoms such as diabetic
      neuropathy and cognitive disorders. Aldose reductase (AR) is the rate-limiting
      enzyme of the polyol pathway and is one of the causal factors of diabetes
      complications. In this study, the bioactivities of eight selected Kampo
      formulations that are currently in clinical use for diabetes complications were
      assessed using human AR (hAR) inhibitory activity as the primary parameter to
      explore the possibilities of novel clinical applications of these formulations in
      the treatment of diabetes complications. METHODS: The hAR inhibitory activities
      of four Kampo formulations that are clinically used for diabetic neuropathy, four
      Kampo formulations that are used for cognitive disorders, and a total of 21
      component crude drugs were measured. Furthermore, the hAR inhibitory activity of
      Glycyrrhizae Radix preparata was measured to determine the effect of frying,
      which is one of the specific processing of Glycyrrhizae Radix. hAR inhibitory
      activity was determined by measuring the rate of decline in the absorbance of
      NAPH at 340 nm using 0.5 mM NADPH, 10 mM D,L-glyceraldehyde, and 3.6 mU/mL hAR in
      phosphate buffer solution (0.2 M, pH 6.2). RESULTS: All of the Kampo formulations
      exhibited significant hAR inhibitory activity; Chotosan exhibited particularly
      strong activity. Among the 21 crude drugs tested, adequate inhibitory activities
      were found for the following, in descending order of activity: Glycyrrhizae Radix
      > Paeoniae Radix > Chrysanthemi Flos > Cinnamomi Cortex > Phellodendri Cortex >
      Uncariae Uncis cum Ramulus > Bupleuri Radix. Glycyrrhizae Radix preparata
      exhibited an inhibitory activity that was nearly identical to that of
      Glycyrrhizae Radix. CONCLUSIONS: Despite their seemingly different treatment
      objectives, all of the Kampo formulations that are clinically used for diabetes
      complications demonstrated significant hAR inhibitory activity. This activity
      might underlie the characteristic multi-target effects of Kampo formulations.
      Although the overall effect of a Kampo formulation is certainly difficult to
      evaluate based on specific herbal medications or components, the approach as
      taken in this study might nonetheless contribute to further advancement in the
      development of new drugs via the review of proper usage and re-examination of the
      chemical compounds from a new perspective.

PMID- 25374325
TI  - The role of disposable inhalers in pulmonary drug delivery.
AB  - INTRODUCTION: There is increasing interest in the pulmonary route for both local
      and systemically acting drugs, vaccines and diagnostics and new applications may
      require new inhaler technology to obtain the most therapeutically and/or cost
      effective administration. Some of these new applications can benefit from the use
      of disposable inhalers. AREAS COVERED: Current trends in pulmonary drug delivery
      are presented in this review as well as the possible contribution of disposable
      inhalers to the improvement of pulmonary administration therein. Arguments in
      favour of disposable inhalers and the starting points for development of devices
      and their formulations are discussed. Also, a brief review of the state of the
      art regarding current disposable inhaler development is given. EXPERT OPINION:
      Prerequisites for the use of disposable inhalers, particularly dry powder
      inhalers, in applications such as childhood vaccination and for preventing or
      stopping pandemic outbreaks of highly infectious diseases (like influenza, bird
      flu, SARS) are that they are simple, cheap and effective. Not only do the devices
      have to be simple in design, but the drug formulations should also be cheap. This
      may require a different approach as the formulation may not need to be adapted to
      improve the inhaler must be designed to enhance formulation dispersion.

PMID- 25374326
TI  - Small supernumerary marker chromosomes and the nuclear architecture of sperm - a
      study in a fertile and an infertile brother.
AB  - Small supernumerary marker chromosomes (sSMC) are found about four times more
      frequently in subfertile compared to the general population. The reason for this
      finding is still unclear. However, a connection of interphase architecture and
      genome function is suggested. And as we found in a previous study the presence of
      sSMC influences the nuclear architecture of peripheral blood cells and
      fibroblasts, we hypothesized that sSMC could have similar effects in sperm cells
      possibly leading to infertility. Here we applied for the first time 3-dimensional
      interphase fluorescence in situ hybridization (3D-FISH) to characterize the
      position of an extra-chromosome with respect to its sister- and selected other
      chromosomes (6, 15, 18, 19, 21, X, and Y) in sperm. Two sSMC carrier brothers
      with the identical sSMC derived from chromosome 15 were studied. One of the
      brothers was fertile and the other brother was infertile. Deviations from the
      normal positioning of chromosomes 21 and Y were seen in both brothers and for
      chromosomes 19 and X only in the infertile brother. Most striking were high rates
      of nullisomy and/or disomy for chromosomes 15, including sSMC (15), and 18
      exclusively seen in the infertile brother. Overall, further evidence is provided
      that sSMC influence the nuclear architecture of a cell, including sperm. Further
      studies are necessary in sperm of fertile and infertile sSMC carriers to
      elaborate if the detected aneuploidy like that seen in the infertile brother is
      due to sSMC presence and disturbance of nuclear architecture.

PMID- 25374324
TI  - Metabolic consequences of interleukin-6 challenge in developing neurons and
      astroglia.
AB  - BACKGROUND: Maternal immune activation and subsequent interleukin-6 (IL-6)
      induction disrupt normal brain development and predispose the offspring to
      developing autism and schizophrenia. While several proteins have been identified
      as having some link to these developmental disorders, their prevalence is still
      small and their causative role, if any, is not well understood. However,
      understanding the metabolic consequences of environmental predisposing factors
      could shed light on disorders such as autism and schizophrenia. METHODS: To gain
      a better understanding of the metabolic consequences of IL-6 exposure on
      developing central nervous system (CNS) cells, we separately exposed developing
      neuron and astroglia cultures to IL-6 for 2 hours while collecting effluent from
      our gravity-fed microfluidic chambers. By coupling microfluidic technologies to
      ultra-performance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM
      MS), we were able to characterize the metabolic response of these CNS cells to a
      narrow window of IL-6 exposure. RESULTS: Our results revealed that 1) the use of
      this technology, due to its superb media volume:cell volume ratio, is ideally
      suited for analysis of cell-type-specific exometabolome signatures; 2) developing
      neurons have low secretory activity at baseline, while astroglia show strong
      metabolic activity; 3) both neurons and astroglia respond to IL-6 exposure in a
      cell type-specific fashion; 4) the astroglial response to IL-6 stimulation is
      predominantly characterized by increased levels of metabolites, while neurons
      mostly depress their metabolic activity; and 5) disturbances in
      glycerophospholipid metabolism and tryptophan/kynurenine metabolite secretion are
      two putative mechanisms by which IL-6 affects the developing nervous system.
      CONCLUSIONS: Our findings are potentially critical for understanding the
      mechanism by which IL-6 disrupts brain function, and they provide information
      about the molecular cascade that links maternal immune activation to
      developmental brain disorders.

PMID- 25374327
TI  - Genetic association study of RNF8 and BRDT variants with non-obstructive
      azoospermia in the Chinese Han population.
AB  - Increasing evidence indicates that polymorphisms in genes relevant to
      spermatogenesis might modulate the efficiency of reproduction in men. Ring finger
      protein 8 (RNF8) and bromodomain testis-specific (BRDT) are two candidate genes
      associated with spermatogenesis. Here, we considered potential associations of 14
      single nucleotide polymorphisms (SNPs) in RNF8 and BRDT genes in Chinese patients
      with non-obstructive azoospermia (NOA). We analyzed 361 men with NOA and 368
      fertile controls by using Sequenom iplex technology. Our data did not reveal any
      variants associated with NOA susceptibility. However, we observed that rs104669
      and rs195432 of RNF8 were in strong linkage disequilibrium. Haplotype analysis of
      the two SNPs indicated that the haplotype AC reduced the risk of NOA and the
      haplotype TC significantly evaluated the risk of NOA. Moreover, the RNF8 variants
      rs195432 (C/A p = 0.030), rs195434 (T/C p = 0.025), and rs2284922 (T/C p = 0.034)
      were correlated with the smaller testis volume.

PMID- 25374328
TI  - Displacement assay detection by a dimeric lanthanide luminescent ternary Tb(III)
      cyclen complex: high selectivity for phosphate and nitrate anions.
AB  - The luminescent dimeric ternary lanthanide-cyclen complexes (2-(Ln.1)2; Ln =
      Tb/Eu) were designed and both their self-assembly formation and their ability to
      detect anions via displacement assays were investigated using spectrophotometric
      titrations in MeOH solution. The formation of 2-(Tb.1)2 and 2-(Eu.1)2 was
      investigated in solution, and determination of the binding constants and
      stoichiometry showed that the former was formed almost exclusively over the 1:1
      complex 2-(Tb.1) after the addition of two equivalents of 2; while for 2-(Eu.1)2
      a mixture of both stoichiometries existed even after the addition of four
      equivalents of 2. Of these two systems, 2-(Tb.1)2 was studied in details as a
      probe for anions, where significant changes where observed in the photophysical
      properties of the complex; with the characteristic Tb(III)-centred emission being
      fully switched off upon the sensing of phosphates and nitrate, giving rise to the
      formation of a H2PO4(-):Tb.1 complex in a 1:2 stoichiometry upon sensing of
      H2PO4(-) by 2-(Tb.1)2, while NO3(-) gave 1:1 complex formation and two
      equivalents of NO3(-).Tb.1.

PMID- 25374329
TI  - Analysis of Thr12Met and Ala1144Thr mutations of the ATP13A2 gene in Parkinson's
      disease patients in Xinjiang Uygur and Han ethnic groups.
AB  - BACKGROUND: It has been reported that the ATP13A2 gene is one of the most
      susceptible pathogenic genes of Parkinson's disease (PD). PARK9 mutations are
      found in early-onset PD and familial PD patients. Uygur and Han PD patients in
      the Xinjiang area were recruited as research subjects to study the differences in
      the Thr12Met and Ala1144Thr loci mutations of the ATP13A2 gene in these PD
      populations. This study explored the mutations at the Thr12Met and Ala1144Thr
      gene loci of the ATP13A2 gene in Parkinson's disease patients in the Uygur and
      Han populations in the Xinjiang province. MATERIAL/METHODS: The polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to
      analyze the Thr12Met and Ala1144Thr mutations of the ATP13A2 gene in a case
      control study of 200 age- and sex- matched Uygur and Han PD patients. RESULTS: Of
      the 200 PD patients were studied, 2 from the Han group had a Thr12Met mutation,
      but Ala1144Thr mutations were not found. Among the Uygur PD patients, no Thr12Met
      or Ala1144Thr mutations were found. CONCLUSIONS: Thr12Met and Ala1144Thr
      mutations of the ATP13A2 gene are rare in the Uygur PD patients in Xinjiang.
      Overall, the mutation rates of Thr12Met and Ala1144Thr in the Uygur and Han PD
      patients in the Xinjiang region are low.

PMID- 25374330
TI  - Are forward bending of the trunk and low back pain associated among Danish blue
      collar workers? A cross-sectional field study based on objective measures.
AB  - The aim of this cross-sectional study was to investigate the association between
      the duration of objectively measured forward bending of the trunk and low back
      pain (LBP) intensity among 198 Danish blue-collar workers (male = 115; female =
      83). The duration of forward bending of >= 30 degrees , >= 60 degrees  and >= 90
      degrees  was divided into high (the highest tertile) and low-moderate (the
      remaining tertiles) categories. High (>5) and low ( <= 5) pain intensities were
      categorised from a self-reported 0-9 scale. Results of multi-adjusted logistic
      regressions indicated no significant positive associations between forward
      bending and LBP intensity. On the contrary, higher duration of forward bending of
      >= 30 degrees  was associated with lower LBP intensity during all day (OR = 0.40;
      95% CI, 0.15-1.02; p = 0.05) and work (OR = 0.44; 95% CI, 0.17-1.15; p = 0.09).
      This indication of a negative association may be explained by fear-avoidance
      behaviour of the blue-collar worker, job crafting or healthy worker effect. 

PMID- 25374331
TI  - Hydrothermal synthesis of ordered mesoporous carbons from a biomass-derived
      precursor for electrochemical capacitors.
AB  - Here, we report the reproducible synthesis of highly ordered mesoporous carbons
      (OMCs) with a 2D hexagonal mesostructure via a facile hydrothermal method
      employing beta-cyclodextrin as a renewable and environmentally-friendly carbon
      precursor, which gives the OMCs a high surface area and micropore surface areas,
      as well as an oxygenated surface. As a supercapacitor electrode, these OMCs
      exhibit a high specific capacitance and a high electrochemical stability. 

PMID- 25374332
TI  - The environmental cost of protein food choices.
AB  - OBJECTIVE: To investigate the resource efficiency and environmental impacts of
      producing one kilogram of edible protein from two plant- and three animal-protein
      sources. DESIGN: Primary source data were collected and applied to commodity
      production statistics to calculate the indices required to compare the
      environmental impact of producing 1 kg of edible protein from kidney beans,
      almonds, eggs, chicken and beef. Inputs included land and water for raising
      animals and growing animal feed, total fuel, and total fertilizer and pesticide
      for growing the plant commodities and animal feed. Animal waste generated was
      computed for the animal commodities. SETTING: Desk-based study at the Department
      of Nutrition and Department of Occupational and Environmental Health, Loma Linda
      University. SUBJECTS: None. RESULTS: To produce 1 kg of protein from kidney beans
      required approximately eighteen times less land, ten times less water, nine times
      less fuel, twelve times less fertilizer and ten times less pesticide in
      comparison to producing 1 kg of protein from beef. Compared with producing 1 kg
      of protein from chicken and eggs, beef generated five to six times more waste
      (manure) to produce 1 kg of protein. CONCLUSIONS: The substitution of beef with
      beans in meal patterns will significantly reduce the environmental footprint
      worldwide and should also be encouraged to reduce the prevalence of non
      communicable chronic diseases. Societies must work together to change the
      perception that red meat (e.g. beef) is the mainstay of an affluent and healthy
      diet.

PMID- 25374333
TI  - Characteristic tandem mass spectral features under various collision chemistries
      for site-specific identification of protein S-glutathionylation.
AB  - Protein S-glutathionylation is a reversible post-translational modification
      widely implicated in redox regulated biological functions. Conventional
      biochemical methods, however, often do not allow such a mixed disulfide
      modification to be reliably identified on specific cysteine residues or be
      distinguished from other related oxidized forms. To develop more efficient mass
      spectrometry (MS)-based analytical strategies for this purpose, we first
      investigated the MS/MS fragmentation pattern of S-glutathionylated peptides under
      various dissociation modes, including collision-induced dissociation (CID),
      higher-energy C-trap dissociation (HCD), and electron transfer dissociation
      (ETD), using synthetic peptides derived from protein tyrosine phosphatase as
      models. Our results indicate that a MALDI-based high energy CID MS/MS on a
      TOF/TOF affords the most distinctive spectral features that would facilitate
      rapid and unambiguous identification of site-specific S-glutathionylation. For
      more complex proteomic samples best tackled by LC-MS/MS approach, we demonstrate
      that HCD performed on an LTQ-Orbitrap hybrid instrument fairs better than trap
      based CID and ETD in allowing more protein site-specific S-glutathionylation to
      be confidently identified by direct database searching of the generated MS/MS
      dataset using Mascot. Overall, HCD afforded more peptide sequence-informative
      fragment ions retaining the glutathionyl modification with less neutral losses of
      side chains to compromise scoring. In conjunction with our recently developed
      chemo-enzymatic tagging strategy, our nanoLC-HCD-MS/MS approach is sufficiently
      sensitive to identify endogenous S-glutathionylated peptides prepared from non
      stressed cells. It is anticipated that future applications to global scale
      analysis of protein S-glutathionylation will benefit further from current
      advances in both speed and mass accuracy afforded by HCD MS/MS mode on the
      Orbitrap series. 

PMID- 25374334
TI  - Immobilized pepsin microreactor for rapid peptide mapping with nanoelectrospray
      ionization mass spectrometry.
AB  - Most enzymatic microreactors for protein digestion are based on trypsin, but
      proteins with hydrophobic segments may be difficult to digest because of the
      paucity of Arg and Lys residues. Microreactors based on pepsin, which is less
      specific than trypsin, can overcome this challenge. Here, an integrated
      immobilized pepsin microreactor (IPMR)/nanoelectrospray emitter is examined for
      its potential for peptide mapping. For myoglobin, equivalent sequence coverage is
      obtained in a thousandth the time of solution digestion with better sequence
      coverage. While sequence coverage of cytochrome c is lesser than solution in this
      short duration, more highly-charged peptic peptides are produced and a number of
      peaks are unidentified at low-resolution, suggesting that high-resolution mass
      spectrometry is needed to take full advantage of integrated IPMR/nanoelectrospray
      devices. 

PMID- 25374335
TI  - Spatial segmentation of MALDI FT-ICR MSI data: a powerful tool to explore the
      head and neck tumor in situ lipidome.
AB  - Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI
      MSI) is a well-established analytical technique for determining spatial
      localization of lipids in biological samples. The use of Fourier-transform ion
      cyclotron resonance (FT-ICR) mass spectrometers for the molecular imaging of
      endogenous compounds is gaining popularity, since the high mass accuracy and high
      mass resolving power enables accurate determination of exact masses and,
      consequently, a more confident identification of these molecules. The high mass
      resolution FT-ICR imaging datasets are typically large in size. In order to
      analyze them in an appropriate timeframe, the following approach has been
      employed: the FT-ICR imaging datasets were spatially segmented by clustering all
      spectra by their similarity. The resulted spatial segmentation maps were compared
      with the histologic annotation. This approach facilitates interpretation of the
      full datasets by providing spatial regions of interest. The application of this
      approach, which has originally been developed for MALDI-TOF MSI datasets, to the
      lipidomic analysis of head and neck tumor tissue revealed new insights into the
      metabolic organization of the carcinoma tissue. 

PMID- 25374336
TI  - Acromegaly: assessing the disorder and navigating therapeutic options for
      treatment.

PMID- 25374337
TI  - Source identification of bacterial and viral pathogens and their survival/fading
      in the process of wastewater treatment, reclamation, and environmental reuse.
AB  - Pathogenic safety is drawing wide concern in water reclamation and reuse. In
      order to elucidate survive/fade of pathogens during the processes of wastewater
      treatment and reclamation, general indicators (fecal coliform and Escherichia
      coli), pathogenic bacteria (Salmonella and Shigella) and viruses (enterovirus,
      rotavirus and norovirus) were investigated in an A(2)O-MBR system. Attention was
      paid to their strengths from different sources, at various stages of the
      treatment, and in the product water. According to findings, black water was the
      main source for pathogens-at least 1-2-log higher in concentration than those
      from other sources. The preliminary treatment of wastewater by fine screens could
      bring about 0.2-0.4-log removal for almost all pathogens. The biological
      treatment units achieved almost identical removal (1.3-1.7-log) for bacteria and
      viruses. However, subsequent treatment in the membrane bioreactor showed varied
      removal for fecal coliform (4.7-log), E. coli (2.6-log) and the other pathogens
      (0.7-1.0-log), indicating that a high reduction of indicator bacteria may not
      imply equivalent removal of bacterial and viral pathogens. Chlorination was
      proved to be effective for eliminating all pathogens. In the artificial lake
      where the product water was stored, fecal coliform was not detected during the
      study period, but E. coli and pathogens were frequently detected, indicating that
      these bacterial and viral pathogens may be originating from non-fecal sources. On
      sunny summer days, the lake water could be bacteria-free due to sunlight
      radiation, but viruses were still detectable. Therefore, secondary disinfection
      may have to be adopted when the reclaimed water stored in such an open reservoir
      is supplied for strict reuse purposes. 

PMID- 25374338
TI  - Child maltreatment and hypertension in young adulthood.
AB  - BACKGROUND: Maltreatment during childhood and adolescence has been associated
      with chronic conditions in adulthood including cardiovascular disease. However,
      less is known about the effects of childhood maltreatment on cardiovascular risk
      factors prior to development of cardiovascular disease, or whether these effects
      are evident in young adulthood. Furthermore, few studies have examined sex
      differences and most studies have relied on self-reported outcome measures that
      are subject to misclassification. METHODS: We examined the relationship between
      child maltreatment and hypertension in young adulthood in the National
      Longitudinal Study of Adolescent Health, a nationally representative school-based
      sample of US adolescents. Participants retrospectively (mean age 29.9, n = 11384)
      reported on their experiences of child maltreatment prior to the 6th grade (prior
      to age 11) during follow-up. Child neglect, physical and sexual violence as well
      as a measure of social services visits to the home were examined. Blood pressure
      was measured during an in-home visit. Hypertension was defined as measured SBP of
      at least 140 mmHg or DBP of at least 90 mmHG measured in adulthood, or self
      reported use of antihypertensive medications. RESULTS: In adjusted models, women
      who experienced sexual abuse in early childhood had a higher prevalence of
      hypertension (Prevalence Ratio (PR) 1.43 95% CI 1.00, 2.05) compared to women who
      did not experience sexual abuse. Among men, experiencing sexual abuse was not
      statistically significantly associated with hypertension. Experiencing neglect,
      physical abuse or having visitations by social services at home during childhood
      was not associated with hypertension among either women or men. CONCLUSION:
      Sexual abuse in early childhood is associated with hypertension in young women.

PMID- 25374339
TI  - An integrated genomic-transcriptomic approach supports a role for the proto
      oncogene BCL3 in atherosclerosis.
AB  - Data with border-line statistical significance, copiously generated in genome
      wide association studies of coronary artery disease (CAD), could include
      functionally relevant associations. We propose an integrated genomic and
      transcriptomic approach for unravelling new potential genetic signatures of
      atherosclerosis. Fifteen among 91 single nucleotide polymorphisms (SNPs) were
      first selected for association in a sex- and age-adjusted model by examining 510
      patients with CAD and myocardial infarction and 388 subjects with normal coronary
      arteries (CAD-free) in the replication stages of a genome-wide association study.
      We investigated the expression of 71 genes proximal to the 15 tag-SNPs by two
      subsequent steps of microarray-based mRNA profiling, the former in vascular
      smooth muscle cell populations, isolated from non-atherosclerotic and
      atherosclerotic human carotid portions, and the latter in whole carotid
      specimens. BCL3 and PVRL2, contiguously located on chromosome 19, and ABCA1,
      extensively investigated before, were found to be differentially expressed. BCL3
      and PVRL2 SNPs were genotyped within a second population of CAD patients (n=442)
      and compared with CAD-free subjects (n=393). The carriership of the BCL3
      rs2965169 G allele was more represented among CAD patients and remained
      independently associated with CAD after adjustment for all the traditional
      cardiovascular risk factors (odds ratio=1.70 with 95% confidence interval 1.07
      2.71), while the BCL3 rs8100239 A allele correlated with metabolic abnormalities.
      The up-regulation of BCL3 mRNA levels in atherosclerotic tissue samples was
      consistent with BCL3 protein expression, which was detected by immunostaining in
      the intima-media of atherosclerotic specimens, but not within non-atherosclerotic
      ones. Our integrated approach suggests a role for BCL3 in cardiovascular
      diseases. 

PMID- 25374341
TI  - Phase II study of olaparib in patients with refractory Ewing sarcoma following
      failure of standard chemotherapy.
AB  - BACKGROUND: Preclinical studies have documented antitumor activity of PARP
      inhibition both in vitro and in vivo, against Ewing sarcoma cells. This study
      aimed to translate that observation into a clinical trial to assess the efficacy
      and tolerability of olaparib, a PARP inhibitor, in patients with advanced Ewing
      sarcoma (EWS) progressing after prior chemotherapy. METHODS: In this
      nonrandomized phase II trial, adult participants with radiographically
      measureable metastatic EWS received olaparib tablets, 400 mg orally twice daily,
      until disease progression or drug intolerance. Tumor measurements were determined
      by CT or MRI at 6 and 12 weeks after starting olaparib administration, and then
      every 8 weeks thereafter. Tumor response determinations were made according to
      RECIST 1.1, and adverse event determinations were made according to CTCAE,
      version 4.0. A total of 22 participants were planned to be enrolled using a
      conventional 2-step phase II study design. If no objective responses were
      observed after 12 participants had been followed for at least 3 months, further
      accrual would be stopped. RESULTS: 12 participants were enrolled, and all were
      evaluable. There were no objective responses (PR/CR), 4 SD (duration 10.9, 11.4,
      11.9, and 17.9 wks), and 8 PD as best response. Of the SD, 2 had minor responses
      (-9% and -11.7% by RECIST 1.1). The median time to disease progression was 5.7
      weeks. Further enrollment was therefore discontinued. No significant or
      unexpected toxicities were observed with olaparib, with only a single case each
      of grade 3 anemia and grade 3 thrombocytopenia observed. CONCLUSIONS: This study
      is the first report of a prospective phase II trial to evaluate the safety and
      efficacy of a PARP inhibitor in patients with advanced Ewing sarcoma after
      failure of standard chemotherapy. Olaparib administration was safe and well
      tolerated when administered to this small heavily pre-treated cohort at the 400
      mg BID dose, although the median duration of dosing was for only 5.7 weeks. No
      significant responses or durable disease control was seen, and the short average
      interval to disease progression underscores the aggressiveness of this disease.
      Other studies to combine cytotoxic chemotherapy with PARP inhibition in EWS are
      actively ongoing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01583543.

PMID- 25374342
TI  - Anti-hepatoma activity of a novel compound glaucocalyxin H in vivo and in vitro.
AB  - Glaucocalyxin H (GLH) is a new compound isolated from a traditional Chinese
      medical herb Isodon japonica var. glaucocalyx which has been used for folk
      medicine. This study was carried out for the first time to investigate the
      potential role of GLH in anti-hepatoma activity and underlying mechanisms in it.
      GLH could inhibit the growth of tumor in mice and induce HepG2 cells to death as
      assessed by the tumor reduction assay, toxic assay, morphological change, and
      survival rate assay. Many antitumor drugs originated from plants could inhibit
      the growth of tumor by inducing cells to apoptosis. The morphological changes of
      HepG2 cells treated with different concentrations of GLH under fluorescence and
      electron microscope and apoptotic rates were detected to verify its effect on
      apoptosis. As shown in the study, GLH could induce HepG2 cells to apoptosis in a
      dose-dependent manner. Bcl2 and Bax proteins played important roles in apoptosis
      and the disequilibrium between Bcl2 and Bax might result in apoptosis. The
      expression of Bax protein was upregulated and Bcl2 protein was downregulated in
      HepG2 cells treated with GLH assessed by Western blotting, and they were in a
      dose-dependent manner. Taken together, GLH can inhibit the growth of hepatoma
      cells in vivo and in vitro by inducing cell apoptosis due to the decreased Bcl2
      and increased Bax proteins suggesting that GLH could be a potential candidate as
      an anti-hepatoma agent for the therapeutic treatment of hepatoma. 

PMID- 25374343
TI  - Simultaneous Determination of Acetaminophen and Synthetic Color(s) by Derivative
      Spectroscopy in Syrup Formulations and Validation by HPLC: Exposure Risk of
      Colors to Children.
AB  - Color additives are used in pediatric syrup formulations as an excipient; though
      not pre-requisite, but pediatric syrup formulations are normally colored. An
      attempt has been made to measure simultaneously the single drug, acetaminophen
      (AT), along with the colors, carmoisine (CA), erythrosine (ET), and sunset yellow
      FCF (SSY) added in it by three derivative spectroscopy methods namely, 1st order,
      ratio, and differential derivative methods. Moreover, evaluation has been made
      for the exposure assessment of the colors added as excipient because some colors
      have been reported to cause allergic reactions and hypersensitivity in children.
      The present methods provide simple, accurate, and reproducible quantitative
      determination of the drug, AT, along with the color in synthetic mixtures and
      commercial drug formulations without any interference. The limit of detection
      varied from 0.0001-0.31 MUg/ml while limit of quantification ranged from 0.002
      1.04 MUg/ml in all the three methods. The calibration curve of all the three
      derivative methods exhibited good linear relationship with excellent regression
      coefficients (0.9986-1.000). Both intra-day and inter-day precisions showed %RSD
      value less than 2% while the percentage recovery was found between 96.8-103.8%.
      The sensitivity of the proposed methods is almost comparable to HPLC and thus,
      can be used for determination of drug AT, and color simultaneously in
      pharmaceutical formulation on routine basis. The present methods also showed that
      colors like SSY and ET are saturating more than 50% of acceptable daily intake
      (ADI) value which is alarming and needs to be considered for modification by
      regulatory authorities to safeguard the health of children.

PMID- 25374344
TI  - Anti-Obesity Effects of Melastoma malabathricum var Alba Linn in Rats Fed with a
      High-Fat Diet.
AB  - Obesity is one of the major public health problems worldwide and it is generally
      associated with many diseases. Although synthetic drugs are available for the
      treatment of obesity, herbal remedies may provide safe, natural, and cost
      effective alternative to synthetic drugs. One example of such drugs is Melastoma
      malabathricum var Alba Linn (MM). Although several studies have been reported for
      the pharmacological activities of MM, there is no report on the anti-obesity
      effect of MM. The aim of the present study is to evaluate the anti-obesity
      potential of methanolic extract of MM. The anti-obesity effect of MM on rats fed
      with a high-fat diet was investigated through determination of the changes in
      body weight, fat weight, organ weights, and blood biochemicals. The animals in
      this study were divided into three groups: a normal group with a standard diet
      (N), a control group fed with high-fat diet (C), and a MM treatment group fed
      with high-fat (HFD + MM) diet for 8 weeks. There was no significant difference in
      the amount of food intake between control and HFD + MM treatments. These results
      also suggest that MM does not induce a dislike for the diet due to its smell or
      taste. The study shows that MM significantly prevented increases in body weight,
      cholesterol, LDL, HDL, and total lipids that resulted from the high-fat diet. MM
      also decreased the epididymal fat (E-fat) and retroperitoneal fat (R-fat) weights
      and phospholipid concentrations induced by the high-fat diet. On the basis of
      these findings, it was concluded that MM had anti-obesity effects by suppressing
      body weight gain and abdominal fat formation. 

PMID- 25374345
TI  - Comments on "a variant pattern of Calretinin immunohistochemistry on rectal
      suction-biopsies is fully specific of short-segment Hirschsprung's disease".

PMID- 25374346
TI  - Evaluation of differences in brain neurophysiology and morphometry associated
      with hand function in individuals with chronic stroke.
AB  - PURPOSE: Rehabilitation interventions need to be optimized to maximize
      therapeutic effects and minimize stroke-related disability. However, a
      comprehensive understanding of the neural substrates underlying recovery is
      lacking. The purpose of this study was to investigate relationships between brain
      anatomy, physiology and hand motor function in individuals with chronic stroke.
      METHODS: Transcranial magnetic stimulation (TMS) and magnetic resonance imaging
      (MRI) approaches were used to evaluate cortical excitability and brain structural
      morphometry in individuals with chronic stroke. Hemispheric differences and
      relationships between these measures and hand dexterity were evaluated. RESULTS:
      Hemispheric differences were observed for TMS and MRI measures. Bilateral hand
      dexterity correlated with TMS resting motor threshold and precentral gyral
      thickness. Transcallosal inhibition across hemispheres was positively associated
      with midcallosal white matter volume. Regression modeling results demonstrated
      that combining TMS and MRI measures predicted unique amounts of variance in hand
      dexterity. CONCLUSIONS: RESULTS confirm and extend findings showing differences
      in brain structure and function after stroke. RESULTS suggested a structure
      function relationship underlying interhemispheric connectivity in chronic stroke.
      The utility of combined TMS and MRI measures to predict motor function can be
      used in future investigations to aid identifying optimal biomarkers of stroke
      recovery to predict response to rehabilitation to maximize treatment outcomes.

PMID- 25374347
TI  - Neural plasticity of voice processing: Evidence from event-related potentials in
      late-onset blind and sighted individuals.
AB  - PURPOSE: Intra- and crossmodal neuroplasticity have been reported to underlie
      superior voice processing skills in congenitally blind individuals. The present
      study used event-related potentials (ERPs) in order to test if such compensatory
      plasticity is limited to the developing brain. METHODS: Late blind individuals
      were compared to sighted controls in their ability to identify human voices. A
      priming paradigm was employed in which two successive voices (S1, S2) of the same
      (person-congruent) or different speakers (person-incongruent) were presented.
      Participants made an old-young decision on the S2. RESULTS: In both groups ERPs
      to the auditory S2 were more negative in person-incongruent than in person
      congruent trials between 200-300 ms. A topographic analysis suggested a more
      posteriorly shifted distribution of the Person Match effect (person-incongruent
      minus person-congruent trials) in late blind individuals compared to sighted
      controls. CONCLUSION: In contrast to congenitally blind individuals, late blind
      individuals did not show an early Person Match effect in the time range of the
      N1, suggesting that crossmodal compensation is mediated by later processing steps
      rather than by changes at early perceptual levels.

PMID- 25374348
TI  - Excess of rare damaging TUBA4A variants suggests cytoskeletal defects in ALS.
AB  - Identifying disease genes implicated in late-onset neurodegenerative disorders
      can be challenging due to the lack of DNA samples from multiple affected family
      members. To overcome this limitation, Smith et al. (2014) report in this issue of
      Neuron the first exome-wide rare variant analysis in unrelated familial
      amyotrophic lateral sclerosis (ALS) patients associating TUBA4A with ALS.

PMID- 25374349
TI  - Chasing the trace.
AB  - Event memories are stored in hippocampal-cortical networks. In this issue of
      Neuron, two studies, Cowansage et al. (2014) and Tanaka et al. (2014), tag active
      cells during memory encoding and optogenetically manipulate the activity of these
      "engram" cells during subsequent recall to reveal how hippocampal and cortical
      cell ensembles interact during retrieval.

PMID- 25374350
TI  - Keeping an eye on cortical states.
AB  - Membrane potential recordings in awake mice have correlated cortical state with
      locomotion and whisker movements. In this issue of Neuron, Reimer et al. (2014)
      now reveal that pupil dilation in stationary mice equally signals a change in
      cortical state and an enhancement of visual processing.

PMID- 25374351
TI  - Concept cells through associative learning of high-level representations.
AB  - In this issue of Neuron, Quian Quiroga et al. (2014) show that neurons in the
      human medial temporal lobe (MTL) follow subjects' perceptual states rather than
      the features of the visual input. Patients with MTL damage however have intact
      perceptual abilities but suffer instead from extreme forgetfulness. Thus, the
      reported MTL neurons could create new memories of the current perceptual state.

PMID- 25374352
TI  - The hippocampal cacophony: multiple layers of communication.
AB  - Locally generated gamma oscillations synchronize spikes, but the nature of
      coupling between regions remains unclear. In this issue of Neuron, Schomburg et
      al. (2014) show that afferent gamma input fails to entrain hippocampal output,
      suggesting limited propagation of gamma waves.

PMID- 25374353
TI  - To simulate or not to simulate: what are the questions?
AB  - Simulation is a powerful method in science and engineering. However, simulation
      is an umbrella term, and its meaning and goals differ among disciplines. Rapid
      advances in neuroscience and computing draw increasing attention to large-scale
      brain simulations. What is the meaning of simulation, and what should the method
      expect to achieve? We discuss the concept of simulation from an integrated
      scientific and philosophical vantage point and pinpoint selected issues that are
      specific to brain simulation. 

PMID- 25374354
TI  - The chronnectome: time-varying connectivity networks as the next frontier in fMRI
      data discovery.
AB  - Recent years have witnessed a rapid growth of interest in moving functional
      magnetic resonance imaging (fMRI) beyond simple scan-length averages and into
      approaches that capture time-varying properties of connectivity. In this
      Perspective we use the term "chronnectome" to describe metrics that allow a
      dynamic view of coupling. In the chronnectome, coupling refers to possibly time
      varying levels of correlated or mutually informed activity between brain regions
      whose spatial properties may also be temporally evolving. We primarily focus on
      multivariate approaches developed in our group and review a number of approaches
      with an emphasis on matrix decompositions such as principle component analysis
      and independent component analysis. We also discuss the potential these
      approaches offer to improve characterization and understanding of brain function.
      There are a number of methodological directions that need to be developed
      further, but chronnectome approaches already show great promise for the study of
      both the healthy and the diseased brain. 

PMID- 25374357
TI  - Generation of human striatal neurons by microRNA-dependent direct conversion of
      fibroblasts.
AB  - The promise of using reprogrammed human neurons for disease modeling and
      regenerative medicine relies on the ability to induce patient-derived neurons
      with high efficiency and subtype specificity. We have previously shown that
      ectopic expression of brain-enriched microRNAs (miRNAs), miR-9/9* and miR-124
      (miR-9/9*-124), promoted direct conversion of human fibroblasts into neurons.
      Here we show that coexpression of miR-9/9*-124 with transcription factors
      enriched in the developing striatum, BCL11B (also known as CTIP2), DLX1, DLX2,
      and MYT1L, can guide the conversion of human postnatal and adult fibroblasts into
      an enriched population of neurons analogous to striatal medium spiny neurons
      (MSNs). When transplanted in the mouse brain, the reprogrammed human cells
      persisted in situ for over 6 months, exhibited membrane properties equivalent to
      native MSNs, and extended projections to the anatomical targets of MSNs. These
      findings highlight the potential of exploiting the synergism between miR-9/9*-124
      and transcription factors to generate specific neuronal subtypes.

PMID- 25374355
TI  - The neurology of mTOR.
AB  - The mechanistic target of rapamycin (mTOR) signaling pathway is a crucial
      cellular signaling hub that, like the nervous system itself, integrates internal
      and external cues to elicit critical outputs including growth control, protein
      synthesis, gene expression, and metabolic balance. The importance of mTOR
      signaling to brain function is underscored by the myriad disorders in which mTOR
      pathway dysfunction is implicated, such as autism, epilepsy, and
      neurodegenerative disorders. Pharmacological manipulation of mTOR signaling holds
      therapeutic promise and has entered clinical trials for several disorders. Here,
      we review the functions of mTOR signaling in the normal and pathological brain,
      highlighting ongoing efforts to translate our understanding of cellular
      physiology into direct medical benefit for neurological disorders. 

PMID- 25374359
TI  - Pupil fluctuations track fast switching of cortical states during quiet
      wakefulness.
AB  - Neural responses are modulated by brain state, which varies with arousal,
      attention, and behavior. In mice, running and whisking desynchronize the cortex
      and enhance sensory responses, but the quiescent periods between bouts of
      exploratory behaviors have not been well studied. We found that these periods of
      "quiet wakefulness" were characterized by state fluctuations on a timescale of 1
      2 s. Small fluctuations in pupil diameter tracked these state transitions in
      multiple cortical areas. During dilation, the intracellular membrane potential
      was desynchronized, sensory responses were enhanced, and population activity was
      less correlated. In contrast, constriction was characterized by increased low
      frequency oscillations and higher ensemble correlations. Specific subtypes of
      cortical interneurons were differentially activated during dilation and
      constriction, consistent with their participation in the observed state changes.
      Pupillometry has been used to index attention and mental effort in humans, but
      the intracellular dynamics and differences in population activity underlying this
      phenomenon were previously unknown. 

PMID- 25374356
TI  - Axonal transport: cargo-specific mechanisms of motility and regulation.
AB  - Axonal transport is essential for neuronal function, and many neurodevelopmental
      and neurodegenerative diseases result from mutations in the axonal transport
      machinery. Anterograde transport supplies distal axons with newly synthesized
      proteins and lipids, including synaptic components required to maintain
      presynaptic activity. Retrograde transport is required to maintain homeostasis by
      removing aging proteins and organelles from the distal axon for degradation and
      recycling of components. Retrograde axonal transport also plays a major role in
      neurotrophic and injury response signaling. This review provides an overview of
      axonal transport pathways and discusses their role in neuronal function. 

PMID- 25374360
TI  - FLRT structure: balancing repulsion and cell adhesion in cortical and vascular
      development.
AB  - FLRTs are broadly expressed proteins with the unique property of acting as
      homophilic cell adhesion molecules and as heterophilic repulsive ligands of
      Unc5/Netrin receptors. How these functions direct cell behavior and the molecular
      mechanisms involved remain largely unclear. Here we use X-ray crystallography to
      reveal the distinct structural bases for FLRT-mediated cell adhesion and
      repulsion in neurons. We apply this knowledge to elucidate FLRT functions during
      cortical development. We show that FLRTs regulate both the radial migration of
      pyramidal neurons, as well as their tangential spread. Mechanistically, radial
      migration is controlled by repulsive FLRT2-Unc5D interactions, while spatial
      organization in the tangential axis involves adhesive FLRT-FLRT interactions.
      Further, we show that the fundamental mechanisms of FLRT adhesion and repulsion
      are conserved between neurons and vascular endothelial cells. Our results reveal
      FLRTs as powerful guidance factors with structurally encoded repulsive and
      adhesive surfaces. 

PMID- 25374358
TI  - Exome-wide rare variant analysis identifies TUBA4A mutations associated with
      familial ALS.
AB  - Exome sequencing is an effective strategy for identifying human disease genes.
      However, this methodology is difficult in late-onset diseases where limited
      availability of DNA from informative family members prohibits comprehensive
      segregation analysis. To overcome this limitation, we performed an exome-wide
      rare variant burden analysis of 363 index cases with familial ALS (FALS). The
      results revealed an excess of patient variants within TUBA4A, the gene encoding
      the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510
      internal controls confirmed the overrepresentation as statistically significant
      and replicable. Functional analyses revealed that TUBA4A mutants destabilize the
      microtubule network, diminishing its repolymerization capability. These results
      further emphasize the role of cytoskeletal defects in ALS and demonstrate the
      power of gene-based rare variant analyses in situations where causal genes cannot
      be identified through traditional segregation analysis.

PMID- 25374362
TI  - The morphological and molecular nature of synaptic vesicle priming at presynaptic
      active zones.
AB  - Synaptic vesicle docking, priming, and fusion at active zones are orchestrated by
      a complex molecular machinery. We employed hippocampal organotypic slice cultures
      from mice lacking key presynaptic proteins, cryofixation, and three-dimensional
      electron tomography to study the mechanism of synaptic vesicle docking in the
      same experimental setting, with high precision, and in a near-native state. We
      dissected previously indistinguishable, sequential steps in synaptic vesicle
      active zone recruitment (tethering) and membrane attachment (docking) and found
      that vesicle docking requires Munc13/CAPS family priming proteins and all three
      neuronal SNAREs, but not Synaptotagmin-1 or Complexins. Our data indicate that
      membrane-attached vesicles comprise the readily releasable pool of fusion
      competent vesicles and that synaptic vesicle docking, priming, and trans-SNARE
      complex assembly are the respective morphological, functional, and molecular
      manifestations of the same process, which operates downstream of vesicle
      tethering by active zone components. 

PMID- 25374361
TI  - Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and
      function of glutamatergic synapses.
AB  - Recent evidence implicates glutamatergic synapses as key pathogenic sites in
      psychiatric disorders. Common and rare variants in the ANK3 gene, encoding
      ankyrin-G, have been associated with bipolar disorder, schizophrenia, and autism.
      Here we demonstrate that ankyrin-G is integral to AMPAR-mediated synaptic
      transmission and maintenance of spine morphology. Using superresolution
      microscopy we find that ankyrin-G forms distinct nanodomain structures within the
      spine head and neck. At these sites, it modulates mushroom spine structure and
      function, probably as a perisynaptic scaffold and barrier within the spine neck.
      Neuronal activity promotes ankyrin-G accumulation in distinct spine subdomains,
      where it differentially regulates NMDA receptor-dependent plasticity. These data
      implicate subsynaptic nanodomains containing a major psychiatric risk molecule,
      ankyrin-G, as having location-specific functions and open directions for basic
      and translational investigation of psychiatric risk molecules. 

PMID- 25374363
TI  - Engagement of neural circuits underlying 2D spatial navigation in a rodent
      virtual reality system.
AB  - Virtual reality (VR) enables precise control of an animal's environment and
      otherwise impossible experimental manipulations. Neural activity in rodents has
      been studied on virtual 1D tracks. However, 2D navigation imposes additional
      requirements, such as the processing of head direction and environment
      boundaries, and it is unknown whether the neural circuits underlying 2D
      representations can be sufficiently engaged in VR. We implemented a VR setup for
      rats, including software and large-scale electrophysiology, that supports 2D
      navigation by allowing rotation and walking in any direction. The entorhinal
      hippocampal circuit, including place, head direction, and grid cells, showed 2D
      activity patterns similar to those in the real world. Furthermore, border cells
      were observed, and hippocampal remapping was driven by environment shape,
      suggesting functional processing of virtual boundaries. These results illustrate
      that 2D spatial representations can be engaged by visual and rotational
      vestibular stimuli alone and suggest a novel VR tool for studying rat navigation.

PMID- 25374364
TI  - Modeling the dynamic interaction of Hebbian and homeostatic plasticity.
AB  - Hebbian and homeostatic plasticity together refine neural circuitry, but their
      interactions are unclear. In most existing models, each form of plasticity
      directly modifies synaptic strength. Equilibrium is reached when the two are
      inducing equal and opposite changes. We show that such models cannot reproduce
      ocular dominance plasticity (ODP) because negative feedback from the slow
      homeostatic plasticity observed in ODP cannot stabilize the positive feedback of
      fast Hebbian plasticity. We propose a model in which synaptic strength is the
      product of a synapse-specific Hebbian factor and a postsynaptic-cell-specific
      homeostatic factor, with each factor separately arriving at a stable inactive
      state. This model captures ODP dynamics and has plausible biophysical substrates.
      We confirm model predictions experimentally that plasticity is inactive at stable
      states and that synaptic strength overshoots during recovery from visual
      deprivation. These results highlight the importance of multiple regulatory
      pathways for interactions of plasticity mechanisms operating over separate
      timescales. 

PMID- 25374367
TI  - Metabolic transformation of indeno[1,2,3-cd]pyrene and toxicities of its
      metabolites.
AB  - A porphyrin/peroxynitrite biomimetic system was used to study the metabolism of
      indeno[1,2,3-cd]pyrene (IND) induced by peroxynitrite. The metabolites were
      identified using high-performance liquid chromatography coupled with electro
      spray ionization tandem mass spectrometry as OH-IND, IND-quinone and 2NO2-IND. By
      stopping the reaction at different stages, we discovered that IND was first
      transformed to IND-quinone and 2NO2-IND, which were then transformed to OH-IND.
      Mutation assays including Ames tests and cell transformation experiments showed
      enhancement of the mutagenicity after the activation by the
      peroxynitrite/Fe(III)porphyrin system. The results also showed that 2NO2-IND and
      IND-quinone played key roles in the mutagenicity of PAHs after metabolic
      activation. 

PMID- 25374368
TI  - Lifetime response of contemporary versus resurrected Daphnia galeata Sars
      (Crustacea, Cladocera) to Cu(II) chronic exposure.
AB  - Resurrecting legacy lineages of organisms from sediment cores of known geological
      age allows us to understand how environmental change can cause selection
      pressures that constrain the variation of populations over time. We quantified
      the lifetime tolerance and effects of Cu(II) exposure on Daphnia galeata in a
      polluted subalpine lake by comparing extant individuals with those resurrected
      from ephippia extracted from ca. 30-years-old sediments. Laboratory experiments
      were conducted using two Cu(II) concentrations, 40 and 10 ug L(-1), corresponding
      to the levels recorded in the lake, during chemical recovery, when Daphnia first
      re-appeared and succeeded. Contemporary Daphnia were unable to survive after the
      10th day at either of the Cu(II) concentrations, and were unable to successfully
      reproduce. Daphnia cohorts from the past performed better in low Cu(II)
      concentrations than in copper-free, control conditions. The copper-adapted,
      tolerant Daphnia strains grew faster under non-toxic conditions, but were unable
      to survive new pollution events.

PMID- 25374366
TI  - Comparative transcriptomics reveals striking similarities between the bovine and
      feline isolates of Tritrichomonas foetus: consequences for in silico drug-target
      identification.
AB  - BACKGROUND: Few, if any, protozoan parasites are reported to exhibit extreme
      organ tropism like the flagellate Tritrichomonas foetus. In cattle, T. foetus
      infects the reproductive system causing abortion, whereas the infection in cats
      results in chronic large bowel diarrhoea. In the absence of a T. foetus genome,
      we utilized a de novo approach to assemble the transcriptome of the bovine and
      feline genotype to identify host-specific adaptations and virulence factors
      specific to each genotype. Furthermore, a subset of orthologs was used to
      characterize putative druggable targets and expose complications of in silico
      drug target mining in species with indefinite host-ranges. RESULTS: Illumina RNA
      seq reads were assembled into two representative bovine and feline transcriptomes
      containing 42,363 and 36,559 contigs, respectively. Coding and non-coding regions
      of the genome libraries revealed striking similarities, with 24,620 shared
      homolog pairs reduced down to 7,547 coding orthologs between the two genotypes.
      The transcriptomes were near identical in functional category distribution; with
      no indication of selective pressure acting on orthologs despite differences in
      parasite origins/host. Orthologs formed a large proportion of highly expressed
      transcripts in both genotypes (bovine genotype: 76%, feline genotype: 56%).
      Mining the libraries for protease virulence factors revealed the cysteine
      proteases (CP) to be the most common. In total, 483 and 445 bovine and feline T.
      foetus transcripts were identified as putative proteases based on MEROPS
      database, with 9 hits to putative protease inhibitors. In bovine T. foetus, CP8
      is the preferentially transcribed CP while in the feline genotype, transcription
      of CP7 showed higher abundance. In silico druggability analysis of the two
      genotypes revealed that when host sequences are taken into account, drug targets
      are genotype-specific. CONCLUSION: Gene discovery analysis based on RNA-seq data
      analysis revealed prominent similarities between the bovine and feline T. foetus,
      suggesting recent adaptation to their respective host/niche. T. foetus represents
      a unique case of a mammalian protozoan expanding its parasitic grasp across
      distantly related host lineages. Consequences of the host-range for in silico
      drug targeting are exposed here, demonstrating that targets of the parasite in
      one host are not necessarily ideal for the same parasite in another host.

PMID- 25374369
TI  - Antibiotics for meconium-stained amniotic fluid in labour for preventing maternal
      and neonatal infections.
AB  - BACKGROUND: Chorioamnionitis is more likely to occur when meconium-stained
      amniotic fluid (MSAF) is present. Meconium may enhance the growth of bacteria in
      amniotic fluid by serving as a growth factor, inhibiting bacteriostatic
      properties of amniotic fluid. Many adverse neonatal outcomes related to MSAF
      result from meconium aspiration syndrome (MAS). MSAF is associated with both
      maternal and newborn infections. Antibiotics may be an effective option to reduce
      such morbidity. OBJECTIVES: The objective of this review is to assess the
      efficacy and side effects of prophylactic antibiotics for MSAF during labour in
      preventing maternal and neonatal infections. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2014). 
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing prophylactic
      antibiotics with placebo or no treatment during labour for women with MSAF. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials for
      inclusion and risk of bias, extracted data and checked them for accuracy. MAIN
      RESULTS: We included two studies with 362 pregnant women. Both studies compared
      ampicillin-sulbactam (N = 183) versus normal saline (N = 179) in pregnant women
      with MSAF. Prophylactic antibiotics appeared to have no statistically significant
      reduction in the incidence of neonatal sepsis (risk ratio (RR) 1.00, 95% CI 0.21
      to 4.76), neonatal intensive care unit (NICU) admission (RR 0.83, 95% CI 0.39 to
      1.78) and postpartum endometritis (RR 0.50, 95% CI 0.18 to 1.38). However, there
      was a significant decrease in the risk of chorioamnionitis (RR 0.36, 95% CI 0.21
      to 0.62). No serious adverse effects were reported. Drug resistance, duration of
      mechanical ventilation and duration of admission to NICU/hospital were not
      reported. Most of the domains for risk of bias were at low risk of bias for one
      study and at unclear risk of bias for the other study. The quality of the
      evidence using GRADE was low for neonatal sepsis, postpartum endometritis, and
      neonatal mortality and morbidity prior to discharge (Neonatal intensive care
      admissions) and of moderate quality for chorioamnionitis. AUTHORS' CONCLUSIONS:
      Current evidence indicates that compared to placebo, antibiotics for MSAF in
      labour may reduce chorioamnionitis. There was no evidence that antibiotics could
      reduce postpartum endometritis, neonatal sepsis and NICU admission. This
      systematic review identifies the need for more well-designed, adequately powered
      RCTs to assess the effect of prophylactic antibiotics in the incidence of
      maternal and neonatal complications.

PMID- 25374370
TI  - Thwarting the Diseased Will: Ulysses Contracts, the Self and Addiction.
AB  - Ulysses contracts are a particular type of advance directive that has been
      advocated for use in mental health settings and addictions treatment. Taking
      their name from the legend of Ulysses, such contracts are distinctive insofar as
      they are designed to thwart certain anticipated future wishes rather than realize
      them. In this paper, I consider what Ulysses contracts reveal about contemporary
      conceptions of addiction and the self. Drawing on discussions of Ulysses
      contracts in the psychiatric and addictions literature, as well as historical and
      contemporary examples of such, I show that Ulysses contracts are premised on a
      split between the present 'rational' self and the future 'irrational' self,
      thereby reproducing a very particular notion of addiction--one that serves to
      naturalize certain ways of thinking about freedom, choice, coercion, and the
      self.

PMID- 25374371
TI  - Role of dual nuclear baths on spin blockade leakage current bistabilities.
AB  - Spin-blockaded electronic transport across a double quantum dot (DQD) system
      represents an important advancement in the area of spin-based quantum
      information. The basic mechanism underlying the blockade is the formation of a
      blocking triplet state. The bistability of the leakage current as a function of
      the applied magnetic field in this regime is believed to arise from the effect of
      nuclear Overhauser fields on spin-flip transitions between the blocking triplet
      and the conducting singlet states. The objective of this paper is to present the
      nuances of considering a two bath model on the experimentally observed current
      bistability by employing a self consistent simulation of the nuclear spin
      dynamics coupled with the electronic transport of the DQD set up. In doing so, we
      first discuss the important subtleties involved in the microscopic derivation of
      the hyperfine mediated spin flip rates. We then give insights as to how the
      differences between the two nuclear baths and the resulting difference Overhauser
      field affect the two-electron states of the DQD and their connection with the
      experimentally observed current hysteresis curve. 

PMID- 25374372
TI  - Inhibitory effect of synthetic cannabinoids on CYP1A activity in mouse liver
      microsomes.
AB  - Synthetic cannabinoids developed by chemical modification are believed to bind to
      cannabinoid receptors and cause neurological effects similar to cannabis;
      however, their effects on drug metabolizing enzymes are unknown. This study aimed
      to elucidate the effect of synthetic cannabinoids on cytochrome P450 1A activity.
      Naphthoylindole, a basic structure of the major synthetic cannabinoids, strongly
      inhibited CYP1A activity in a competitive manner; the apparent Ki value was 0.40
      MUM. The N-Alkylated derivatives of naphthoylindole, MAM-2201 and JWH-019, also
      inhibited CYP1A activity in a concentration-dependent manner; however, their
      inhibitory effects were weaker than naphthoylindole. An adamantylamidoindole
      derivative, STS-135, showed inhibition of CYP1A activity in a
      concentrationdependent manner, but the adamantoylindole derivatives, AB-001 and
      AM-1248, did not. A tetramethylcyclopropanoylindole derivative, UR-144, showed a
      weak inhibition of CYP1A activity at high concentrations. These results suggest
      that synthetic cannabinoids and their basic molecules are capable of inhibiting
      CYP1A enzymatic activity. 

PMID- 25374373
TI  - Effect of talaporfin sodium-mediated photodynamic therapy on cell death
      modalities in human glioblastoma T98G cells.
AB  - While photodynamic therapy (PDT) is an effective treatment for glioma, induction
      of apoptotic cell death of glioma cells is important for ensuring efficacy and
      safety of PDT treatment in glioma patients, as necrotic cell death can induce
      late appearance of obstacles in treatment. Here, we investigated the relationship
      between type of cell death and PDT treatment conditions involved in laser and
      photosensitizer dosage in human glioblastoma T98G cells. Photosensitizer
      talaporfin sodium-mediated PDT (NPe6-PDT) treatment induced laser and NPe6 dose
      dependent cell death in T98G cells, whereas almost all cells pretreated with NPe6
      at >= 30 ug/mL were killed by laser irradiation, regardless of laser dose.
      Morphological analysis showed that combination of high doses of NPe6 and laser
      irradiation changes the dominant cell death process from apoptosis to necrosis.
      Biochemical analysis (detection of caspase-3 activity and staining of cell
      surface-exposed phosphatidylserine) also showed that increasing laser dose
      changes the type of cell death from apoptotic to necrotic cell death after high
      dose treatment with NPe6. Lactate dehydrogenase leakage assay demonstrated that a
      laser dose of 5 J/cm(2) induced less leakage than 30 J/cm(2). Our results
      suggested that type of glioma cell death in NPe6-PDT changed with fluctuations in
      laser and NPe6 dose, and that combination of 30 ug/mL NPe6 with 5 J/cm(2) laser
      is the best treatment condition for inducing an increase in apoptotic cells while
      keeping rate of necrotic cell death low in this in vitro study. 

PMID- 25374374
TI  - Cypermethrin induced behavioral and biochemical changes in mahseer, Tor putitora.
AB  - The purpose of this study was to evaluate behavioral responses and biochemical
      changes induced by the extensively used pesticide cypermethrin (CYP) in liver,
      gills, brain and muscle tissues of mahseer (Tor putitora) fry. Behavioral changes
      in fish after exposure to an acute concentration of CYP involved jumping, abrupt
      swimming, loss of balance and equilibrium, increased surface activity and air
      gulping. These changes were more prominent with the passage of time. After a
      longer period of exposure, the fish became sluggish and before dying occasionally
      became motionless and sometimes showed a vertical position. Internal hemorrhage
      was also obvious. CYP exposure resulted in a significant decrease in total
      protein content in different tissues while antioxidant enzymes, catalase (CAT),
      peroxidase (POD) and glutathione reductase (GR) showed a time-dependent
      increasing trend in their activities in liver, brain, gills and muscle tissues.
      Similarly, lipid peroxidation (LPO) level also increased with time in different
      tissues of CYP-exposed fish. The results of the present study revealed that CYP
      is toxic to the mahseer Tor putitora. Therefore, its indiscriminate use can
      contribute in decreasing the population of mahseer in natural water bodies. 

PMID- 25374375
TI  - Comprehensive analysis of DNA methylation and gene expression of rat liver in a 2
      stage hepatocarcinogenesis model.
AB  - Recent studies have shown that epigenetic alterations correlate with
      carcinogenesis in various tissues. Identification of these alterations might help
      characterize the early stages of carcinogenesis. We comprehensively analyzed DNA
      methylation and gene expression in livers obtained from rats exposed to
      nitrosodiethylamine (DEN) followed by a promoter of hepatic carcinogenesis,
      phenobarbital (PB). The combination of DEN and PB induced marked increases in
      number and area of glutathione S-transferase-placental form (GST-P)-positive foci
      in the liver. In the liver of rats that received 30 mg/kg of DEN, pathway
      analysis revealed alterations of common genes in terms of gene expression and DNA
      methylation, and that these alterations were related to immune responses.
      Hierarchical clustering analysis of the expression of common genes from public
      data obtained through the Toxicogenomics Project-Genomics Assisted Toxicity
      Evaluation system (TG-GATEs) showed that carcinogenic compounds clustered
      together. MBD-seq and GeneChip analysis indicated that major histocompatibility
      complex class Ib gene RT1-CE5, which has an important role in antigen
      presentation, was hypomethylated around the promoter region and specifically
      induced in the livers of DEN-treated rats. Further, immunohistochemical analysis
      indicated that the co-localization of GST-P and protein homologous to RT1-CE5 was
      present at the foci of some regions. These results suggest that common genes were
      altered in terms of both DNA methylation and expression in livers, with
      preneoplastic foci indicating carcinogenic potential, and that immune responses
      are involved in early carcinogenesis. In conclusion, the present study identified
      a specific profile of DNA methylation and gene expression in livers with
      preneoplastic foci. Early epigenetic perturbations of immune responses might
      correlate with the early stages of hepatocarcinogenesis. 

PMID- 25374376
TI  - Antigenotoxic capacity of beta-caryophyllene in mouse, and evaluation of its
      antioxidant and GST induction activities.
AB  - The present report was designed to determine the antigenotoxic capacity of beta
      caryophyllene (BC) on the damage induced by benzo(a)pyrene (BaP) in mouse. We
      found no genotoxic potential of BC, and a significant inhibitory effect on the
      number of sister-chromatid exchanges (SCE) and chromosomal aberrations induced by
      BaP. The three tested doses of the agent (20, 200, and 2,000 mg/kg) produced a
      dose-dependent decrease of the two evaluated cytogenetic parameters. In
      comparison with the effect induced by BaP, the best inhibitory effect (about 80%)
      was obtained with the high tested dose of BC considering the two evaluated
      parameters. Other aim of the study was to explore whether in this effect
      participated the BC antioxidant capacity and/or its effect as inducer of GST
      activity. We found a dose-dependent decrease induced by BC in regard to both the
      oxidation of lipids and proteins produced by BaP.In the case of GST, when BC was
      administered alone we found a mean increase of 64% of the enzyme activity,
      respect to the control level, and when BC was administered in mice treated with
      BaP the increase obtained with the high dose of BC reached 27%. Therefore, our
      data established no in vivo genotoxicity by BC, and a significant antigenotoxic
      potential of the compound, which may be related with its capacity to block the
      molecular oxidation and to stimulate the GST activity. 

PMID- 25374377
TI  - FBXO6 attenuates cadmium toxicity in HEK293 cells by inhibiting ER stress and JNK
      activation.
AB  - Cadmium-induced cell death is associated with endoplasmic reticulum (ER) stress.
      We previously found that inhibition of FBXO6 expression, which is a ubiquitin
      ligase involved in ER-associated protein degradation (ERAD), induces high
      sensitivity to cadmium in HEK293 cells. However, the precise role of FBXO6 in ER
      stress remains unexplored. In this study, we investigated the role of FBXO6 in
      cadmium-induced ER stress in HEK293 cells. Our results showed that the cadmium
      induced increase in expression of the ER stress marker proteins, BiP and CHOP,
      was further enhanced by inhibiting FBXO6 expression. Cadmium-induced c-Jun
      phosphorylation was also markedly increased by inhibition of FBXO6 expression.
      However, this c-Jun phosphorylation was almost entirely abolished by inhibition
      of c-Jun N-terminal kinase 1 (JNK1) expression. The level of high cadmium
      sensitivity induced by inhibition of FBXO6 expression was markedly lower in the
      JNK1-ablated cells than in the control cells. In addition, cadmium elevated the
      cellular level of ERAD substrate proteins, and this elevation was further
      enhanced by inhibiting FBXO6 expression. These results suggest that FBXO6 might
      inhibit cadmium-induced ER stress by functioning as a ubiquitin ligase in the
      ERAD system, thereby attenuating the cell death induced by subsequent JNK1
      activation. 

PMID- 25374378
TI  - Student perspectives of an online module for teaching physical assessment skills
      for dentistry, dental hygiene, and pharmacy students.
AB  - The integration of web-based learning into the curriculum of healthcare education
      has significantly increased over the past decade. This article aims to describe
      the student perspectives of an online module to teach physical assessment skills
      for pharmacy, dentistry, and dental hygiene students. A total of 103 students
      completed the online module: 48 third-year pharmacy students, 29 first-year
      dentistry students, and 26 first-year dental hygiene students. Students were
      asked to rate a list of 10 statements on a 5-point Likert scale on the relevance,
      impact, and overall satisfaction of the online module. Eighty-four of the 103
      students (81.6% response rate) completed the questionnaire. While most students
      responded positively to the online content, pharmacy students responded more
      favorably compared with students from Dentistry and Dental Hygiene. These
      findings provide useful information to identify areas in which the web-based
      module can be improved for teaching skills in physical assessment across multiple
      healthcare programs. 

PMID- 25374379
TI  - Sediment toxicity and bioaccumulation assessment in abandoned copper and mercury
      mining areas of the Nalon River basin (Spain).
AB  - Sediment toxicity and metal bioaccumulation were assessed at sites affected by
      historical copper (Cu) and mercury (Hg) mining activities in the Nalon River
      basin, Asturias, Spain. Toxicity assessment of stream sediments was based on a 28
      day oligochaete Tubifex tubifex sediment bioassay, which allowed the
      classification of sites into three levels of toxicity: 11 sites were classified
      as nontoxic (including Cu mine sites), three sites as potentially toxic, and
      seven sites as toxic (all located in Hg mine districts). The greatest levels of
      arsenic (As), chromium, Hg, lead (Pb), and zinc (Zn) in T. tubifex were measured
      at sites affected by Hg mining and the highest Cu levels in tissues at Cu mining
      sites. Chronic toxicity responses were best explained by As and Hg sediment
      concentrations and by As, Pb, and Zn tissue residues. Residue levels of As, Hg,
      Zn, and Pb were successfully used to predict sediment chronic toxicity and
      estimate effective tissue residues. 

PMID- 25374380
TI  - A porcine early-onset scoliosis model created using a posterior mini-invasive
      method: a pilot study.
AB  - STUDY DESIGN: An animal study. OBJECTIVE: To create a reliable porcine scoliosis
      model representative of early-onset scoliosis (EOS) without violation of the
      vertebral elements along the curve. SUMMARY OF THE BACKGROUND DATA: To develop
      new nonfusion techniques for the treatment of EOS, a reliable large animal model
      with remarkable growth potential is required. However, a long tethering period
      which consumed the majority of the rapid growth phase or violation of the
      vertebral elements was thought to be essential in most of the previous models.
      Therefore, these models may be suboptimal for mimics of human EOS which was
      usually idiopathic type without vertebral anomalies. MATERIALS AND METHODS: This
      study included 12 female Yorkshire pigs (aged, 5-6 wk; weight, 5-7 kg) in which
      scoliosis was created by posterior asymmetric tethering from T5 to L3. At the
      index surgery, 3 separate incisions were preformed, and ipsilateral rib tethering
      from the 10th to the 13th rib was performed while maintaining the vertebral
      elements along the maximal curve in a pristine state. Progressive deformity was
      documented with monthly radiographs. Frontal and sagittal profiles were assessed
      using the Cobb method. After an 8-week tethering period, the whole
      instrumentations were removed, and the pigs were observed for an additional 8
      week period with serial radiographs to document the progression of the deformity.
      RESULTS: Of the 12 pigs enrolled in this study, 2 encountered substantial
      complications (1 developed a postoperative infection, and the other experienced
      prolonged postoperative weakness). Of the 10 available for analysis, all pigs
      developed rapidly progressive, structurally 3-dimensional, idiopathic-type curves
      with convex to the right in the lower thoracic spine. The mean coronal Cobb angle
      was 29 degrees immediately postoperatively and progressed to 65 degrees after the
      8-week tethering period. Eight weeks after removal of the tether, the scoliosis
      continued to progress and averaged 68 degrees (range, 58-78 degrees). On the
      sagittal plane, a mean lordosis of 32 degrees at the thoracic spine and a
      thoracolumbar kyphosis of 63 degrees were observed at study completion.
      CONCLUSIONS: A 3-dimensional rapidly progressive scoliosis model, that is closely
      approximate to human EOS, can be successfully created in pigs by unilaterally
      tethering the thoracolumbar spine and the ribcage. This model provides an
      equivalent EOS-like deformity and leaves adequate skeletal growth potential for
      biomechanical research as well as validation of fusionless scoliosis correction
      systems.

PMID- 25374381
TI  - Posterior Cervicothoracic Instrumentation: Testing the Clinical Efficacy of
      Tapered Rods (Dual-Diameter Rods).
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To study the clinical efficacy of
      tapered rods in posterior cervicothoracic instrumentation. SUMMARY OF BACKGROUND
      DATA: The cervicothoracic spine is a junctional area with complex biomechanics. A
      variety of disorders affect this region, rendering it unstable. Numerous
      posterior constructs have been evaluated by in vitro biomechanical studies. There
      are no data available on the clinical efficacy of a screw-rod system utilizing
      tapered (dual-diameter) rods. This is the first study analyzing the efficacy of
      this system in clinical scenarios in the short term. MATERIALS AND METHODS: All
      consecutive patients with cervicothoracic junctional pathologies undergoing
      surgical treatment by posterior instrumentation utilizing tapered rods, between
      April 2007 and April 2012 were included in the study. The tapered rod tapers from
      a diameter of 5.5-3.5 mm to accommodate thoracic pedicle screws and lateral mass
      screws/pedicle screws of cervical spine, respectively. The cases were
      periodically followed up. Postoperative radiographs and computed tomography scans
      were analyzed. RESULTS: There were 14 cases, 11 males and 3 females. The etiology
      was tuberculosis in 7 cases, neoplasm in 5, and 1 each of trauma and deformity.
      Three patients required combined anterior and posterior surgeries and remaining
      10 were managed by posterior-only procedures. The average follow-up was 28
      months. Three patients died (surgically unrelated reasons) and 1 was lost to
      follow-up. Excluding 2 patients with neoplastic and traumatic etiologies,
      patients with neurological deficit had significant improvement. One patient had
      postoperative cerebrospinal fluid leak which was recognized and corrected
      subsequently. No biomechanical failure occurred in any of the patients. No
      intraoperative complications were noted. CONCLUSIONS: This study demonstrates
      that tapered rods are an excellent and a viable option to connect screws to
      stabilize cervicothoracic junction in the short term. This study complements the
      biomechanical studies previously reported.

PMID- 25374382
TI  - How well do Radiologic Assessments of Truncal and Shoulder Balance Correlate With
      Cosmetic Assessment Indices in Lenke 1C Adolescent Idiopathic Scoliosis?
AB  - STUDY DESIGN: A correlation study. OBJECTIVE: The primary objective was to
      determine the correlation between radiologic and cosmetic indices of trunk and
      shoulder balance before and after scoliosis surgery in Lenke 1C adolescent
      idiopathic scoliosis and to determine whether postoperative trunk shift is
      affiliated with worsening of the patients' cosmesis. SUMMARY OF BACKGROUND DATA:
      Achieving a symmetrical appearance with truncal and shoulder balance is of prime
      importance to adolescent idiopathic scoliosis patients and their surgeons.
      However, surgeons prefer radiographic indices rather than measures of patients'
      clinical appearance. If radiographic indices are to be considered accurate
      depictions of the patient's cosmesis, radiologic and cosmetic indices must
      necessarily exhibit high association. METHODS: Radiographic and cosmetic indices
      of trunk and shoulder balance, along with posterior trunk symmetry index, were
      measured preoperatively and 3 months postoperatively in 33 Lenke 1C scoliosis
      patients. Pearson correlation analysis was performed. Paired t test was used to
      determine significant changes in radiographic and cosmetic indices after surgery.
      Independent-sample t test was used for all intergroup analyses in trunk shift and
      no-trunk-shift groups. RESULTS: Correlation coefficients between radiologic and
      cosmetic indices ranged between -0.63 and 0.70 with thoracic apical vertebra
      central sacral vertical line (AV-CSVL) distance and first rib angle showing
      consistent correlations with cosmetic trunk and cosmetic shoulder balance
      indices. Trunk shift, a postoperative iatrogenic phenomenon, was seen in 19 (58%)
      patients. These patients had higher preoperative thoracic AV-CSVL translation,
      thoracic apical vertebra-first thoracic vertebra (AV-T1) translation, thoracic
      deformity correction rate, AV-T1 correction rates, and shorter fusions compared
      with the no-trunk-shift group. Posterior trunk symmetry index worsened in trunk
      shift group and improved significantly (-7.94 vs. 16.53) in no-trunk-shift group.
      Significant association (P=0.004) was seen between radiographic and cosmetic
      trunk shift. CONCLUSIONS: Radiographic indices can only minisculely (r<=0.7)
      reflect cosmetic deformity in Lenke 1C scoliosis, which emphasizes not only the
      vulnerability of overreliance on radiographic indices but also the vital
      importance of clinical cosmetic evaluations. In particular, cosmetic shoulder
      height and angle are not represented by radiographic indices. However, radiograph
      trunk shift was significantly associated with cosmetic trunk shift in cosmetic
      pictures.

PMID- 25374383
TI  - Extracellular vesicles derived from mesenchymal stem cells induce features of
      diabetic retinopathy in vitro.
AB  - AIMS: Loss of pericytes in the early phases of diabetic retinopathy (DR) may
      disrupt their stable association with endothelial cells (EC), leading to EC
      proliferation and, eventually, angiogenesis. Extracellular vesicles (EV) are
      small membrane particles derived from different cells which contain biologically
      active proteins and RNA and are known to promote phenotypic changes in target
      cells. In diabetic-like conditions, EV derived from MSC may play a role in vessel
      destabilization by interfering with the strict interactions between EC/pericytes
      and pericyte/extracellular matrix. METHODS: We examined the behaviour of retinal
      pericytes exposed to EV derived from MSC cultured in physiological and diabetic
      like conditions (high glucose and/or hypoxia). RESULTS: MSC-derived EV are able
      to enter the pericytes, cause their detachment and migration from the substrate,
      and increase blood-barrier permeability. Moreover, EV added to EC/pericytes co
      cultures in Matrigel promote in vitro angiogenesis. These effects may be mediated
      by matrix metalloproteinase-2, expressed by both EV and EV-stimulated pericytes,
      and are exacerbated if MSC are previously cultured in conditions (high glucose
      and/or hypoxia) mimicking the diabetic microvascular milieu. CONCLUSIONS: We
      confirm that MSC-derived EV contribute to angiogenesis, showing that they may not
      only exert a direct stimulus to EC proliferation, but also induce pericyte
      detachment, thus leaving EC free to proliferate. In addition, we demonstrate a
      possible link between EV and the early stages of the pathogenesis of DR. Diabetic
      like conditions may influence vessel remodelling during angiogenesis through EV
      paracrine signalling.

PMID- 25374384
TI  - Xenin-25[Lys13PAL]: a novel long-acting acylated analogue of xenin-25 with
      promising antidiabetic potential.
AB  - AIMS: Xenin-25 is co-secreted with glucose-dependent insulinotropic polypeptide
      (GIP) from intestinal K-cells following a meal. Xenin-25 is believed to play a
      key role in glucose homoeostasis and potentiate the insulinotropic effect of GIP.
      METHODS: This study investigated the effects of sub-chronic administration of the
      stable and longer-acting xenin-25 analogue, xenin-25[Lys(13)PAL] (25 nmol/kg), in
      diabetic mice fed with a high-fat diet. RESULTS: Initial studies confirmed the
      significant persistent glucose-lowering (p < 0.05) and insulin-releasing (p <
      0.05) actions of xenin-25[Lys(13)PAL] compared with native xenin-25.
      Interestingly, xenin-25 retained significant glucose-lowering activity in GIP
      receptor knockout mice. Twice-daily intraperitoneal (i.p.) injection of xenin
      25[Lys(13)PAL] for 14 days had no significant effect on food intake or body
      weight in high-fat-fed mice. Non-fasting glucose and insulin levels were also
      unchanged, but overall glucose levels during an i.p. glucose tolerance and oral
      nutrient challenge were significantly (p < 0.05) lowered by xenin-25[Lys(13)PAL]
      treatment. These changes were accompanied by significant improvements in i.p. (p
      < 0.05) and oral (p < 0.001) nutrient-stimulated insulin concentrations. No
      appreciable changes in insulin sensitivity were observed between xenin
      25[Lys(13)PAL] and saline-treated high-fat mice. However, xenin-25[Lys(13)PAL]
      treatment restored notable sensitivity to the biological actions of exogenous GIP
      injection. Consumption of O2, production of CO2, respiratory exchange ratio and
      energy expenditure were not altered by 14-day twice-daily treatment with xenin
      25[Lys(13)PAL]. In contrast, ambulatory activity was significantly (p < 0.05 to p
      < 0.001) increased during the dark phase in xenin-25[Lys(13)PAL] mice compared
      with high-fat controls. CONCLUSIONS: These data indicate that sustained
      administration of a stable analogue of xenin-25 exerts a spectrum of beneficial
      metabolic effects in high-fat-fed mice.

PMID- 25374385
TI  - Apolipoprotein B/apolipoprotein A1 ratio and non-high-density lipoprotein
      cholesterol. Predictive value for CHD severity and prognostic utility in CHD
      patients.
AB  - BACKGROUND AND AIMS: To explore the clinical value of the combination of
      apolipoprotein B/apolipoprotein A1 (apoB/A1) and non-high-density lipoprotein
      cholesterol (HDL-C) in evaluating the severity of coronary heart disease (CHD)
      and in predicting in-hospital CHD events and the long-term prognosis of CHD
      patients. METHODS: According to the results of coronary angiography, 826 patients
      were enrolled and classified into a CHD group (532 cases, including single-branch
      stenosis group, n = 165; double-branch stenosis group, n = 175;and multi-branch
      stenosis group, n = 192) and a normal group (294 cases). The serum apoB/apoA1
      ratio and non-HDL-C were calculated at baseline. The Gensini score and logistic
      regression were applied to analyze the association between the apoB/apoA1 ratio,
      non-HDL-C, and the severity of CHD. Major in-hospital adverse incidents were
      recorded and follow-up telephone interviews were conducted 3 years after
      discharge. RESULTS: Both the apoB/apoA1 ratio and non-HDL-C rose with the number
      of stenotic coronary branches. Only apoB and apoB/apoA1 remained significantly
      associated with the risk of multi-branches lesions and the Gensini score after
      adjustment. Patients with combined high levels of apoB/apoA1 and non-HDL-C (N =
      50, 43.10 %) suffered from the highest risk of multi-branches lesions. Similarly,
      patients with combined high levels of apoB/apoA1 and non-HDL-C not only suffered
      from the highest risk of in-hospital new-onset heart failure and cardiac death
      (16.38 % vs. 10.35 %), but also had the highest risk of adverse events, angina,
      myocardial infarction, new-onset heart failure, stroke, and cardiac death after
      an average 3-year follow-up. CONCLUSION: The combination of apoB/apoA1 and non
      HDL-C is predictive of the severity of CHD, and it could provide more prognostic
      information than its individual components or other routine lipid profiles.

PMID- 25374386
TI  - Guideline-adherent therapy in patients with acute coronary syndromes. The EPICOR
      registry in Germany.
AB  - BACKGROUND: Representative data on the current management of patients with acute
      coronary syndromes (ACS) are of high interest. The EPICOR registry aimed to
      prospectively collect such real-life data with particular focus on antithrombotic
      drug utilization and outcomes. METHODS: As part of the international prospective
      EPICOR registry, 29 hospitals in Germany documented 296 patients with ST
      elevation myocardial infarction (STEMI)-ACS and 333 with unstable angina or non
      STEMI (NSTEMI)-ACS surviving the hospital phase. The statistical analysis was
      performed in a descriptive manner. The ClinicalTrials.gov identifier is
      NCT01171404. RESULTS: The mean age of patients was 62 +/- 13 years, and 77.4 %
      were men. Treatment with antithrombotic agents was initiated in the prehospital
      phase in 50.7 % of STEMI and 33.3 % of NSTEMI patients. During the hospital stay
      (median 7.0 days), cardiac catheterization was performed in 97.6 %, percutaneous
      coronary intervention in 85.6 %, thrombolysis in 4.6 %, and coronary bypass
      surgery in 2.7 % patients. The use of acetylic salicylic acid (ASA) was reported
      in 95.6 % vs. 96.1 %, clopidogrel in 60.8 % vs. 73.0 %, prasugrel in 45.6 % vs.
      22.5 %, any GP IIb/IIIa inhibitor in 52.4 % vs. 18.9 % [any dual combination of
      ASA+(clopidogrel/prasugrel)in 94.0 vs. 91.0 %], statins in 94.6 % vs. 92.2 %,
      beta blockers in 96.3 % vs. 94.6 %, and ACE-I/ARB in 91.6 % vs. 87.7 % of STEMI
      vs. NSTEMI patients, respectively. Combined use of the five drug classes
      recommended in the guidelines-ASA, P2Y12 antagonists, statin, beta blocker, and
      ACE-I/ARB-was reported in 81.1 % vs. 69.4 % of STEMI vs. NSTEMI patients,
      respectively. CONCLUSION: In Germany a high proportion of patients with ACS are
      treated according to current guidelines, receiving primary revascularization as
      well as antithrombotic drugs and other agents for prevention of secondary events;
      associated bleeding complications were less frequent as compared with published
      registries.

PMID- 25374387
TI  - Vertical segregation in the self-assembly of nanoparticles at the liquid/air
      interface.
AB  - Vertical segregation was induced by the size-dependent charge neutralization
      during the one-step interfacial self-assembly of colloidal gold nanoparticles
      with bimodal size distribution. This self-assembly approach also can assemble
      particles with tunable compositions into layered films. 

PMID- 25374388
TI  - Attenuation of cystitis and pain sensation in mice lacking fatty acid amide
      hydrolase.
AB  - Endocannabinoids, such as N-arachidonoylethanolamine (AEA, also called
      anandamide), exert potent analgesic and anti-inflammatory effects. Fatty acid
      amide hydrolase (FAAH) is primarily responsible for degradation of AEA, and
      deletion of FAAH increases AEA content in various tissues. Since FAAH has been
      shown to be present in the bladder of various species, we compared bladder
      function, severity of experimental cystitis, and cystitis-associated referred
      hyperalgesia in male wild-type (WT) and FAAH knock-out (KO) mice. Basal
      concentrations of AEA were greater, and the severity of cyclophosphamide (CYP)
      induced cystitis was reduced in bladders from FAAH KO compared to WT mice.
      Cystitis-associated increased peripheral sensitivity to mechanical stimuli and
      enhanced bladder activity (as reflected by increased voiding frequency) were
      attenuated in FAAH KO compared to WT mice. Further, abundances of mRNA for
      several pro-inflammatory compounds were increased in the bladder mucosa after CYP
      treatment of WT mice, and this increase was inhibited in FAAH KO mice. These data
      indicate that endogenous substrates of FAAH, including the cannabinoid AEA, play
      an inhibitory role in bladder inflammation and subsequent changes in pain
      perception. Therefore, FAAH could be a therapeutic target to treat clinical
      symptoms of painful inflammatory bladder diseases. 

PMID- 25374389
TI  - Conformation and dynamics of 8-Arg-vasopressin in solution.
AB  - Arginine-vasopressin was subjected to a long (11 MUs) molecular dynamics
      simulation in aqueous solution. Analysis of the results by DASH and principal
      components analyses revealed four main ring conformations that move essentially
      independently of the faster-moving tail region. Two of these conformations
      (labeled "saddle") feature well-defined beta-turns in the ring and conserved
      transannular hydrogen bonds, whereas the other two ("open") feature neither. The
      conformations have been identified and defined and are all of sufficient
      stability to be considered candidates for biological conformations in their
      cognate receptors. 

PMID- 25374390
TI  - Characteristics of protein residue-residue contacts and their application in
      contact prediction.
AB  - Contact sites between amino acids characterize important structural features of a
      protein. We investigated characteristics of contact sites in a representative set
      of proteins and their relations between protein class or topology. For this
      purpose, we used a non-redundant set of 5872 protein domains, identically
      categorized by CATH and SCOP databases. The proteins represented alpha, beta, and
      alpha+beta classes. Contact maps of protein structures were obtained for a
      selected set of physical distances in the main backbone and separations in
      protein sequences. For each set a dependency between contact degree and distance
      parameters was quantified. We indicated residues forming contact sites most
      frequently and unique amino acid pairs which created contact sites most often
      within each structural class. Contact characteristics of specific topologies were
      compared to the characteristics of their protein classes showing protein groups
      with a distinguished contact characteristic. We showed that our results could be
      used to improve the performance of recent top contact predictor - direct coupling
      analysis. Our work provides values of contact site propensities that can be
      involved in bioinformatic databases. 

PMID- 25374391
TI  - Three model shapes of Doxorubicin for liposome encapsulation.
AB  - Targeted drug delivery provides a possible method for the transfer of drug
      molecules into cancer cells. Liposomes together with a drug, such as Doxorubicin
      (DOX) inside the liposomes, can be formed as a nano-capsule. In this study, we
      are interested in finding a favorable size of liposome and an appropriate shape
      of DOX cluster: sphere, cylinder or ellipsoid. Using mathematical modeling, the
      interaction energy of the system is obtained from the Lennard-Jones potential and
      the continuum assumption which assumes that discrete atomic structure can be
      replaced by an average atomic density spread over a surface. The numerical
      results show that the spherical shape gives the lowest energy at the equilibrium
      configuration amongst the three shapes. In the case of equivalent surface areas,
      the spherical shape gives the energy lower than -4,000 kJ/mol at the equilibrium
      while the energies for the other cases do not come close to this level. Further
      in the case of a liposome of 50 nm in radius, the sphere of radius 49.726 nm,
      equivalent to 31,072 nm(2) surface area, gives the minimum energy at -6,642
      kJ/mol. However, an equivalent cylindrical shape is not possible due to geometric
      constraints. The lowest minimum energy for the ellipsoid occurs for equal major
      and minor axes, namely for the spherical case. The results presented here are a
      first step in the design and implementation of a drug molecule for a targeted
      drug delivery system. 

PMID- 25374392
TI  - Association of single nucleotide polymorphisms in the USF1, GTF2A1L and OR2W3
      genes with non-obstructive azoospermia in the Chinese population.
AB  - PURPOSE: To research the association between the single nucleotide polymorphisms
      (SNPs) of three spermatogenesis-related genes (USF1, GTF2A1L and OR2W3) and non
      obstruction azoospermia (NOA). METHODS: We investigated 361 NOA cases and 368
      controls from the Chinese Han population, and we used Sequenom iplex technology
      to analyze the candidate 9 SNPs from the USF1, GTF2A1L and OR2W3 genes. RESULTS:
      In this study, we found that the variant rs2516838 of USF1 was associated with
      NOA susceptibility (P = 0.020, OR = 1.436), and the haplotype TCG of the variants
      rs1556259, rs2516838, and rs2774276 of USF1 conferred an increased risk of NOA (P
      = 0.019, OR = 1.436). Furthermore, we found that the rs11204546 genotype of OR2W3
      and the rs11677854 genotype of GTF2A1L were correlated with the FSH level in the
      patients (P = 0.004 and P = 0.018, respectively). CONCLUSIONS: Our results
      provided a new insight into susceptibility of USF1 variant with male infertility.
      Clinically, the SNPs (rs11204546 of OR2W3 and rs11677854 of GTF2A1L ) might be
      additional valuable molecular predictive markers for assessing the treatment of
      NOA patients.

PMID- 25374393
TI  - DNA fragmentation in human sperm after magnetic-activated cell sorting.
AB  - PURPOSE: As fertilization with unselected apoptotic spermatozoa may contribute to
      failures in assisted reproductive techniques, it has become essential to remove
      this type of sperm in order to increase the success rates. Magnetic-activated
      cell sorting (MACS) is a sperm preparation technique that isolates non-apoptotic
      spermatozoa based on the expression of phosphatidylserine in the membrane of
      apoptotic sperm. Therefore, we aimed to evaluate whether there was a significant
      decrease in sperm DNA fragmentation (sDNAfrag) and verify which protocol was the
      most efficient. METHODS: Hundred semen samples were allocated into five distinct
      groups and processed according to a combination of MACS with density gradient
      centrifugation (DGC) and swim-up (SU) techniques. Sperm DNA fragmentation was
      evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)
      assay. RESULTS: Groups DGC-SU (73.4 %), DGC-MACS-SU (78.9 %), DGC-SU-MACS (53.8
      %) and MACS-SU (73.5 %) presented a significant decrease in sDNAfrag but the
      highest reduction rate was obtained with MACS-DGC-SU (83.3 %). The later was also
      negatively correlated with sperm vitality, membrane integrity and progressive
      motility. Additionally, teratozoospermic patients presented a tendency to have
      lower sDNAfrag reduction rates than asthenozoospermic and asthenoteratozoospermic
      patients. CONCLUSIONS: Based on the results, MACS showed potential to optimize
      the sDNAfrag reduction rate, when applied to raw semen, before DGC and SU,
      especially in samples with low values of progressive motility, vitality and
      hypoosmotic swelling test.

PMID- 25374395
TI  - An infertile 45,X male with a SRY-bearing chromosome 13: a clinical case report
      and literature review.
AB  - PURPOSE: Patients with a karyotype of 45,X (monosomy X) normally display a female
      phenotype. However, in some rare cases, monosomy X is associated with maleness.
      Here we describe a case of a male with a 45,X karyotype and primary infertility,
      which prompted molecular investigation of the sex-determination gene SRY.
      METHODS: Karyotyping was performed by GTG-banded chromosome analysis. The
      presence and location of SRY was investigated using PCR and FISH, respectively.
      RESULTS: PCR confirmed the presence of the SRY gene while FISH analysis
      demonstrated its location on the p arm of chromosome 13. These findings
      demonstrate that autosomal retention of SRY can be sub-microscopic and emphasize
      the importance of PCR and FISH in the genetic workup of the monosomic X male.

PMID- 25374394
TI  - Follicular fluid lipid fingerprinting from women with PCOS and hyper response
      during IVF treatment.
AB  - PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that
      leads to lower natural reproductive potential and presents a challenge for
      assisted reproductive medicine because patients may exhibit immature oocyte
      retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro
      fertilization (IVF) treatment. This study aimed to identify potential lipid
      biomarkers for women with PCOS and a hyper response to controlled ovarian
      stimulation. METHODS: Follicular fluid samples were collected from patients who
      underwent IVF, including normal responder women who became pregnant (control
      group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS
      group, n = 7) and women with only hyper response to gonadotropins (HR group, n =
      7). A lipidomic analysis was performed by electrospray ionization mass
      spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry
      experiment. RESULTS: The lipid profiles indicated particularities related to
      differences in phosphatidylcholine (PCOS and HR), phosphatidylserine,
      phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and
      phosphatidylethanolamine (control and HR). CONCLUSIONS: These findings contribute
      to the understanding of the molecular mechanisms associated with lipid metabolism
      in the PCOS-related hyper response, and strongly suggest that these lipids may be
      useful as biomarkers, leading to the development of more individualized treatment
      for pregnancy outcome.

PMID- 25374396
TI  - Effect of single embryo transfer on the risk of preterm birth associated with in
      vitro fertilization.
AB  - PURPOSE: To determine whether elective single embryo transfer (eSET) reduces the
      risk of preterm delivery associated with in vitro fertilization (IVF). METHODS:
      This is an observational study of 3125 eSET cycles performed from 2008 to 2009
      and reported to the Society for Assisted Reproductive Technology (SART) database.
      Preterm delivery rates were compared to the overall preterm delivery rate among
      all patients undergoing IVF over the same time period. RESULTS: The 3125 eSET
      cycles resulted in 1507 live births (live birth rate 48.2 %) Among these
      deliveries were 27 twins (1.8 %) and one set of triplets (0.07 %). The overall
      preterm delivery rate (20-37 weeks gestation) following eSET was 17.6 %
      (269/1527). This is significantly greater than the preterm birth rate for all
      patients undergoing IVF over the same time period (12 %, P < 0.001). CONCLUSIONS:
      Elective single embryo transfer does not reduce the risk of preterm delivery
      associated with in vitro fertilization (IVF).

PMID- 25374398
TI  - Skin, soft tissue and systemic bacterial infections following aquatic injuries
      and exposures.
AB  - : Bacterial infections following aquatic injuries occur commonly in fishermen and
      vacationers after freshwater and saltwater exposures. Internet search engines
      were queried with the key words to describe the epidemiology, clinical
      manifestations, diagnostic and treatment strategies and outcomes of both the
      superficial and the deeper invasive infections caused by more common, newly
      emerging and unusual aquatic bacterial pathogens. Main findings included the
      following: (1) aquatic injuries often result in gram-negative polymicrobial
      infections with marine bacteria; (2) most marine bacteria are resistant to 1st-
      and 2nd-generation penicillins and cephalosporins; (3) nontuberculous,
      mycobacterial infections should be considered in late-onset, culture-negative and
      antibiotic-resistant marine infections; (4) superficial marine infections and pre
      existing wounds exposed to seawater may result in deeply invasive infections and
      sepsis in immunocompromised patients. With the exception of minor marine wounds
      demonstrating localized cellulitis, most other marine infections and all gram
      negative and mycobacterial marine infections will require therapy with antibiotic
      combinations. 

PMID- 25374397
TI  - Construction of a high-performance magnetic enzyme nanosystem for rapid tryptic
      digestion.
AB  - A magnetic enzyme nanosystem have been designed and constructed by a polydopamine
      (PDA)-modification strategy. The magnetic enzyme nanosystem has well defined core
      shell structure and a relatively high saturation magnetization (Ms) value of 48.3
      emu g(-1). The magnetic enzyme system can realize rapid, efficient and reusable
      tryptic digestion of proteins by taking advantage of its magnetic core and
      biofunctional shell. Various standard proteins (e.g. cytochrome C (Cyt-C),
      myoglobin (MYO) and bovine serum albumin (BSA)) have been used to evaluate the
      effectiveness of the magnetic enzyme nanosystem. The results show that the
      magnetic enzyme nanosystem can digest the proteins in 30 minutes, and the results
      are comparable to conventional 12 hours in-solution digestion. Furthermore, the
      magnetic enzyme nanosystem is also effective in the digestion of low
      concentration proteins, even at as low as 5 ng MUL(-1) substrate concentration.
      Importantly, the system can be reused several times, and has excellent stability
      for storage. Therefore, this work will be highly beneficial for the rapid
      digestion and identification of proteins in future proteomics. 

PMID- 25374400
TI  - The effect of exposure to biomass smoke on respiratory symptoms in adult rural
      and urban Nepalese populations.
AB  - BACKGROUND: Half of the world's population is exposed to household air pollution
      from biomass burning. This study aimed to assess the relationship between
      respiratory symptoms and biomass smoke exposure in rural and urban Nepal.
      METHODS: A cross-sectional study of adults (16+ years) in a rural population (n =
      846) exposed to biomass smoke and a non-exposed urban population (n = 802) in
      Nepal. A validated questionnaire was used along with measures of indoor air
      quality (PM2.5 and CO) and outdoor PM2.5. RESULTS: Both men and women exposed to
      biomass smoke reported more respiratory symptoms compared to those exposed to
      clean fuel. Women exposed to biomass were more likely to complain of ever wheeze
      (32.0 % vs. 23.5%; p = 0.004) and breathlessness (17.8% vs. 12.0%, p = 0.017)
      compared to males with tobacco smoking being a major risk factor. Chronic cough
      was similar in both the biomass and non-biomass smoke exposed groups whereas
      chronic phlegm was reported less frequently by participants exposed to biomass
      smoke. Higher PM2.5 levels (>=2 SDs of the 24-hour mean) were associated with
      breathlessness (OR = 2.10, 95% CI 1.47, 2.99) and wheeze (1.76, 1.37, 2.26).
      CONCLUSIONS: The study suggests that while those exposed to biomass smoke had
      higher prevalence of respiratory symptoms, urban dwellers (who were exposed to
      higher ambient air pollution) were more at risk of having productive cough.

PMID- 25374401
TI  - Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation
      in vaginal atrophy?
AB  - OBJECTIVES: The primary objective of this study was to evaluate the correlation
      among symptoms, signs, and the number of lactobacilli in postmenopausal vaginal
      atrophy. The secondary objective was to develop a new parameter to improve the
      correlation. STUDY DESIGN: A cross-sectional descriptive study. METHODS:
      Naturally postmenopausal women aged 45-70 years with at least one clinical
      symptom of vaginal atrophy of moderate to severe intensity were included in this
      study. All of the objective parameters (vaginal atrophy score, vaginal pH, the
      number of lactobacilli, vaginal maturation index, and vaginal maturation value)
      were evaluated and correlated with vaginal atrophy symptoms. A new parameter of
      vaginal atrophy, vaginal atrophy symptoms II, was developed and consists of the
      two most bothersome symptoms (vaginal dryness and dyspareunia). Vaginal atrophy
      symptoms II was analyzed for correlation with the objective parameters. RESULTS:
      A total of 132 naturally postmenopausal women were recruited for analysis.
      Vaginal pH was the only objective parameter found to have a weak correlation with
      vaginal atrophy symptoms (r = 0.273, p = 0.002). The newly developed vaginal
      atrophy symptoms II parameter showed moderate correlation with vaginal pH (r =
      0.356, p < 0.001) and a weak correlation with the vaginal atrophy score (r =
      0.230, p < 0.001). History of sexual intercourse within 3 months was associated
      with a better correlation between vaginal atrophy symptoms and the objective
      parameters. CONCLUSION: Vaginal pH was significantly correlated with vaginal
      atrophy symptoms. The newly developed vaginal atrophy symptoms II was associated
      with a better correlation. The vaginal atrophy symptoms II and vaginal pH may be
      better tools for clinical evaluation and future study of the vaginal ecosystem.

PMID- 25374402
TI  - The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge
      Weber syndrome.
AB  - Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by
      capillary malformation (port-wine stains), and choroidal and leptomeningeal
      vascular malformations. Previously, the recurrent somatic mutation c.548G>A
      (p.R183Q) in the G-alpha q gene (GNAQ) was identified as causative in SWS and non
      syndromic port-wine stain patients using whole-genome sequencing. In this study,
      we investigated somatic mutations in GNAQ by next-generation sequencing. We first
      performed targeted amplicon sequencing of 15 blood-brain-paired samples in
      sporadic SWS and identified the recurrent somatic c.548G>A mutation in 80% of
      patients (12 of 15). The percentage of mutant alleles in brain tissues of these
      12 patients ranged from 3.6 to 8.9%. We found no other somatic mutations in any
      of the seven GNAQ exons in the remaining three patients without c.548G>A. These
      findings suggest that the recurrent somatic GNAQ mutation c.548G>A is the major
      determinant genetic factor for SWS and imply that other mutated candidate gene(s)
      may exist in SWS. 

PMID- 25374403
TI  - A case of pharyngeal injury in a patient with swallowed toothbrush: a case
      report.
AB  - BACKGROUND: Otolaryngologists encounter cases of various foreign bodies in the
      oral and pharyngeal regions. One commonly found foreign body is a fish bone,
      ingested in most cases by carelessness or an accident. These foreign materials
      are removed by endoscopy or through a simple procedure. However, hypopharyngeal
      damage is rarely caused by a foreign body in the pharynx following the swallowing
      of a toothbrush. CASE PRESENTATION: A 44-year-old Asian male visited the
      emergency room with chief complaints of intraoral pain and dysphagia that had
      started on the same day. The patient had paranoid-type schizophrenia that began
      10 years ago; he had been hospitalized and was being treated at another clinic,
      and was transferred to the emergency room by the medical staff after swallowing a
      toothbrush. We successfully removed a toothbrush located within the pharynx of a
      patient with a history of a psychologic disorder via surgery and conservative
      treatment. CONCLUSION: The case with this patient, and a rapid diagnosis as well
      as treatment is imperative. The presence and state of a foreign body must be
      determined through a careful physical examination and imaging, followed by the
      immediate removal of the foreign body, all while keeping in mind the possibility
      of accompanying damage to nearby tissues.

PMID- 25374404
TI  - Abuse-deterrent formulations: part 1 - development of a formulation-based
      classification system.
AB  - INTRODUCTION: Strategies have been implemented to decrease the large proportion
      of individuals misusing abusable prescription medications. Abuse-deterrent
      formulations (ADFs) have been grown to incorporate many different technologies
      that still lack a systematic naming and organizational nomenclature. Without a
      proper classification system, it has been challenging to properly identify ADFs,
      study and determine common traits or characteristics and simplify communication
      within the field. AREAS COVERED: This article introduces a classification system
      for all ADF approaches and examines the physical, chemical and pharmacological
      characteristics of a formulation by placing them into primary, secondary and
      tertiary categories. Primary approaches block tampering done directly to the
      product. Secondary approaches work in vivo after the product is administered.
      Tertiary approaches use materials that discourage abuse but do not stop
      tampering. Part 2 of this article discusses proprietary technologies, patents and
      products utilizing primary approaches. EXPERT OPINION: Drug products using opioid
      antagonists and aversive agents have been seen over the past few decades to
      discourage primarily overuse and injection. However, innovation in formulation
      development has introduced products capable of deterring multiple forms of
      tampering and abuse. Often, this is accomplished using known excipients and
      manufacturing methods that are repurposed to prevent crushing, extraction and
      syringeability.

PMID- 25374405
TI  - The place of Slovakian paternal diversity in the clinal European landscape.
AB  - BACKGROUND: Several demographic events have been postulated to explain the
      contemporaneous structure of European genetic diversity. First, an initial
      settlement of the continent by anatomically modern humans; second, the re
      settlement of northern latitudes after the Last Glacial Maximum; third, the demic
      diffusion of Neolithic farmers from the Near East; and, fourth, several
      historical events such as the Slavic migration. AIM: The aim of this study was to
      provide a more integrated picture of male-specific genetic relationships of
      Slovakia within the broader pan-European genetic landscape. SUBJECTS AND METHODS:
      This study analysed a new Y-chromosome data-set (156 individuals) for both SNP
      and STR polymorphisms in population samples from five different Slovakian
      localities. RESULTS: It was found that the male diversity of Slovakia is embedded
      in the clinal pattern of the major R1a and R1b clades extending over the
      continent and a similar pattern of population structure is found with Y-specific
      SNP or STR variation. CONCLUSION: The highly significant correlation between the
      results based on fast evolving STRs on one hand and slow evolving SNPs on the
      other hand suggests a recent timeframe for the settlement of the area.

PMID- 25374406
TI  - A cheap and facile route to synthesize monodisperse magnetic nanocrystals and
      their application as MRI agents.
AB  - A facile solution-based thermal decomposition strategy, using very cheap
      polyisobutylene succimide (PIBSI) and paraffin oil as a surfactant and solvent,
      respectively, has been developed for the controllable synthesis of magnetic
      MnFe2O4 and CoFe2O4 nanocrystals (NCs) with high dispersibility, uniform shape,
      and high yield. By fine-tuning the reaction temperature and growth time, the
      morphology and size of MnFe2O4 and CoFe2O4 NCs can be simply regulated. It is
      found that the surfactant PIBSI plays a key role in the final shape of the
      products due to its long chain with non-polar groups, which can markedly hinder
      the aggregation of the NCs and thus greatly improve the stability and
      dispersibility of the products. The results reveal that MnFe2O4 and CoFe2O4 NCs
      have good biocompatibility and obvious T2 contrast enhancement effects have been
      achieved with the increase of iron concentration. MnFe2O4 and CoFe2O4 NCs show
      high longitudinal relaxivity of 165.6 and 65.143 mM(-1) S(-1) in aqueous
      solutions due to the positive signal enhancement ability of Fe(3+) ions,
      indicating the highly potential to be used as effective T2 contrast agents for
      magnetic resonance imaging (MRI). 

PMID- 25374407
TI  - Phase I clinical trial of temsirolimus and vinorelbine in advanced solid tumors.
AB  - PURPOSE: To determine the maximal tolerated dose (MTD) of the combination of
      weekly temsirolimus and every other week vinorelbine in patients with advanced or
      refractory solid tumors. METHODS: Patients were treated with intravenous
      temsirolimus on days 1, 8, 15, and 22 and intravenous vinorelbine on days 1 and
      15. Cycles were repeated every 28 days. RESULTS: Nineteen patients were enrolled
      in the study. Tumor types included lung (5), prostate (2), neuroendocrine of
      pancreas (1), bladder (2), uterus (3), cervix (4), and vagina (2). All patients
      had received prior chemotherapy. Four patients were enrolled to dose level I,
      nine to dose level II, and six to dose level III. Six patients were inevaluable
      and replaced. Fifty-seven total cycles were administered. There was 1 dose
      limiting toxicity at level II (grade 3 anorexia/dehydration) and 2 at level III
      (grade 3 hypokalemia; grade 4 neutropenia). Two patients died at dose level III;
      one was study-related with grade 4 neutropenia. Grade 3/4 toxicities observed
      during the first cycle included neutropenia (2), anemia (1), anorexia (1),
      dehydration (1), hyperglycemia (1), hypertriglyceridemia (1), and hypokalemia
      (1). Best response included two patients (prostate and non-small cell lung
      cancer) with partial response and eight patients with stable disease with median
      duration of best response of 3.2 months. CONCLUSIONS: Temsirolimus 25 mg given
      days 1, 8, 15, and 22 in combination with vinorelbine 20 mg/m(2) given days 1 and
      15 every 4 weeks was found to be the MTD. This dose combination is considered
      feasible in phase II trials.

PMID- 25374409
TI  - Predictive factors for survival in stage IIIA N2 NSCLC patients treated with
      neoadjuvant CCRT followed by surgery.
AB  - PURPOSE: To assess the impact of imaging, surgical, histopathologic and patient
      related factors on the risks of recurrence and overall survival (OS) in stage
      IIIA-N2 non-small cell lung cancer (NSCLC) patients undergoing definitive
      resection after neoadjuvant concurrent chemoradiotherapy (CCRT). METHODS: We
      retrospectively examined 104 consecutive patients with stage IIIA-N2 NSCLC who
      received neoadjuvant CCRT followed by surgery between 2008 and 2011. While
      reviewing the clinical and surgical data, we also assessed histopathologic and
      imaging (CT and PET/CT) factors. Disease-free survival (DFS) and OS were
      estimated with predictors for recurrence and survival. RESULTS: The 3-year OS for
      patients with and without recurrence was 37.1 and 63.3 %, respectively (p <
      0.001). Size decrease of target lesion(s) >=36 % on post-neoadjuvant CCRT CT (p =
      0.048) and viable tumor size on surgical specimen <9.4 mm (p = 0.035) were
      related to longer OS. Regarding shorter DFS, tumor size on post-neoadjuvant CCRT
      CT (p = 0.046), SUV(max) of the primary tumor (p = 0.011), male gender (p =
      0.023), total tumor size on surgical specimen (p = 0.041) and viable tumor size
      on surgical specimen (p = 0.043) were the significant predictors. CONCLUSIONS: OS
      is prolonged with greater extent of size decrease of target lesion(s) on post
      neoadjuvant CCRT CT and smaller viable tumor size on surgical specimen. Larger
      tumor size on post-neoadjuvant CCRT CT, higher SUV(max), male gender, larger
      total tumor size and larger viable tumor size on surgical specimen may herald the
      higher probability of recurrence and the necessity of more attention.

PMID- 25374408
TI  - Population pharmacokinetic/dynamic model of lymphosuppression after fludarabine
      administration.
AB  - PURPOSE: Quantitative relationships between 9-beta-D-arabinofuranosyl-2
      fluoroadenine (F-ara-A) concentrations and lymphosuppression have not been
      reported, but would be useful for regimen design. A population
      pharmacokinetic/pharmacodynamic model was constructed in this study using data
      from 41 hematopoietic cell transplant (HCT) recipients conditioned with busulfan
      in combination with fludarabine (total dose 120 mg/m2, Protocol 1519) or with
      fludarabine (total dose 250 mg/m2) with rabbit antithymocyte globulin (rATG,
      Protocol 2041). METHODS: Individual pharmacokinetic parameters were fixed to post
      hoc Bayesian estimates, and circulating absolute lymphocyte counts (ALC) were
      obtained during the 3 weeks prior to graft infusion. A semi-physiological cell
      kill model with three lymphocyte transit compartments was applied and aptly
      characterized the time course of suppression of circulating ALC by fludarabine
      administration. Drug- and system-specific parameters were estimated using a
      maximum likelihood expectation maximization algorithm, and the final model was
      qualified using an internal visual predictive check. RESULTS: The final model
      successfully characterized the time course and variability in ALC.
      Pharmacodynamic parameters exhibited considerable between subject variability
      (38.9-211 %). The HCT protocol was the only covariate associated with the
      pharmacodynamic parameters, specifically the lymphocyte kill rate, the transit
      rate between lymphocyte compartments, and the baseline ALC. CONCLUSIONS: This
      model can be used to simulate the degree of lymphosuppression for design of
      future fludarabine-based conditioning regimens.

PMID- 25374410
TI  - Safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with
      chronic myeloid leukemia treated with dasatinib: a case report.
AB  - PURPOSE: The safety of S-1 in recurrent colorectal cancer patients with chronic
      myeloid leukemia (CML) treated with dasatinib has not been established. We
      evaluated the safety and pharmacokinetics of S-1 in a recurrent colon cancer
      patient with CML treated with dasatinib. PATIENT: A 70-year-old man had undergone
      surgery three times for sigmoid colon cancer and recurrence. Systemic
      chemotherapy with S-1 plus oxaliplatin plus bevacizumab as a clinical trial had
      already been administered because of metastatic colon cancer. The patient's
      medical history was CML, and he had been receiving dasatinib treatment (100 mg
      once daily). Based on the diagnosis of unresectable and multiple metastases, S-1
      monotherapy was started. S-1 (120 mg/day) was taken for 28 consecutive days,
      followed by a 14-day rest. Blood samples were obtained before and after the first
      administration of S-1. The plasma pharmacokinetics of S-1 were comparable to a
      pharmacokinetics study of S-1. RESULTS: The area under the plasma concentration
      time curve (AUC0-8) of tegafur (FT), 5-chloro-2, 4-dihydroxypyridine (CDHP),
      oxonate (Oxo), and 5-fluorouracil (5-FU) was 4,309.2, 716.3, 86.8, and 492.75 ng
      h/mL, respectively, after S-1 administration. The pharmacokinetics of FT, CDHP,
      Oxo, and 5-FU after treatment with S-1 were not significantly different from a
      phase I pharmacokinetics study of S-1. During treatment with S-1 and dasatinib,
      CML relapse and serious myelosuppression were not observed. CONCLUSIONS: Our
      report suggests that S-1 is an important treatment option for recurrent
      colorectal cancer in patients with CML treated with dasatinib.

PMID- 25374411
TI  - Experiences with ascending aortic endografts using FDA IDE approved devices. What
      has been done, what lesions can be treated and what challenges remain.
AB  - Thoracic endovascular aortic repair (TEVAR) has become an attractive treatment
      option for thoracic aortic disease. New devices and advanced image-guided
      procedures are continuously expanding the indications. With improving device
      technology, diverse stent-graft availability, and imaging modalities, TEVAR has
      become safer and holds promising potential to expand treatment options,
      especially for ascending aorta and aortic arch pathology. This article focuses on
      current evolving endovascular solutions for thoracic ascending aortic diseases
      and starts with an overview of historical TEVAR landmarks, followed by
      indications for TEVAR, and concludes with present day challenges. 

PMID- 25374412
TI  - Association of Romo1 gene genetic polymorphisms with risk of gastric cancer in
      northwestern Chinese population.
AB  - Increased expression of reactive oxygen species modulator 1 protein-triggered
      reactive oxygen species production was reported in the mitochondria of various
      cancer cell lines. To date there is no report on association between Romo1 gene
      polymorphisms and gastric cancer risk. To investigate the relationship between
      Romo1 gene polymorphisms and GC risk, we conducted a case-control study in a
      population from northwest China (358 GC patients and 412 healthy controls). The
      genotypes of two SNPs were determined with PCR-denaturing high-performance liquid
      chromatography and direct DNA sequencing. We found that the genotype and allele
      distributions of two polymorphisms were significantly different in GC patients
      compared with controls, When the wild type of two loci were served as the
      reference group, respectively, significantly increased risk for gastric cancer
      were associated with rs6060566 TC genotype (Adjusted OR = 1.525, 95 % CI =1.126
      2.138), rs6060567 GC genotype (Adjusted OR = 1.641, 95 % CI =1.238-2.291) and CC
      genotype (Adjusted OR = 1.594, 95 % CI =1.102-2.973). This effect was more
      pronounced in patients with smoking, alcohol consumption, H.pylori infection,and
      male patients subgroups. Haplotypes analysis of two genetic variants showed that
      the most common haplotype TG displayed the strongest evidence of association with
      GC (corrected P = 9.30 * 10(-5)), and was associated with protection against GC
      (OR = 0.584). Whereas the CC haplotypes had significant correlation with GC risk
      (OR = 1.732). These findings suggested genetic polymorphisms of Romo1 gene were
      associated with significant risk of GC in Northwestern Chinese population, which
      is strengthened by alcohol use, smoking, H.pylori infection or male patients.

PMID- 25374414
TI  - Hypoglycemia and clinical outcomes in patients with diabetes mellitus admitted to
      the general ward in a hospital in singapore.

PMID- 25374415
TI  - Laparoscopic surgery, a better approach for elderly patients with colorectal
      cancer.

PMID- 25374416
TI  - Tuberculosis: a perennial pain in the posterior?

PMID- 25374417
TI  - Intestinal lymphoma--a review of the management of emergency presentations to the
      general surgeon.
AB  - INTRODUCTION: Intestinal non-Hodgkin's lymphoma (NHL) is uncommon but not rare.
      This paper aims to review the recent evidence for the management of perforated
      NHL of the intestine, consider when chemotherapy should be commenced and examine
      the likely outcomes and prognosis for patients presenting as surgical emergencies
      with this condition. METHODS: MEDLINE and Cochrane databases were searched using
      intestinal lymphoma, clinical presentation, perforation, management and
      prognosis. The full text of relevant articles was retrieved and reference lists
      checked for additional articles. FINDINGS: Emergency surgery was required at
      disease presentation for between 11 and 64% of intestinal NHL cases. Perforation
      occurs in 1-25% of cases, and also occurs whilst on chemotherapy for NHL.
      Intestinal bleeding occurs in 2-22% of cases. Obstruction occurs more commonly in
      small bowel (5-39%) than large bowel NHL and intussusceptions occur in up to 46%.
      Prognosis is generally poor, especially for T cell lymphomas. CONCLUSIONS: There
      is a lack of quality evidence for the elective and emergency treatment of NHL
      involving the small and large intestine. There is a lack of information regarding
      the impact an emergency presentation has on the timing of postoperative
      chemotherapy and overall prognosis. It is proposed that in order to develop
      evidence-based treatment protocols, there should be an intestinal NHL registry.

PMID- 25374418
TI  - Maintenance of the rate of stair use over a long-term period using a stair
      climbing campaign.
AB  - OBJECTIVE: This study was a long-term survey of a stair climbing campaign that
      made use of point-of-choice prompts aimed at achieving exemplary behavior in
      citizens. METHODS: The campaign began in September 2007 at the Kochi Prefectural
      Office. We monitored office workers who climbed the stairs or used the elevator
      in the prefectural office building, excluding weekends, from August 2007 through
      February 2009. Prompts were placed on the stair risers. A total of 59 days were
      monitored during the observation period. A questionnaire was distributed to 250
      workers to examine the influence of the prompts following completion of the
      observation period. RESULTS: A total of 16,583 observations of the choice of
      workers to use the elevators or stairs were made during the observation period.
      The mean number of stair users was 281.0 +/- 66.0 per day. Stair use increased
      significantly from 31.5 to 58.1% among women and from 26.3 to 62.4% among men
      during months 1-3 of the campaign. Stair use was maintained in more than 51% of
      women and 60% of men during the entire campaign period. The following response
      (valid records: 81) was given by 10% of the respondents regarding the use of
      stairs: "my use of stairs increased due to the message banners". CONCLUSIONS: The
      stair climbing campaign was effective for increasing stair use and was maintained
      over a long-term period. However, most office workers thought that their
      increased stair use was not due to prompts placed on risers; therefore, the
      reason for the increased stair use remains unclear.

PMID- 25374419
TI  - Metabolic rate prediction in young and old men by heart rate, ambient
      temperature, weight and body fat percentage.
AB  - OBJECTIVES: An estimation of metabolic rate (MR) is needed to determine wet-bulb
      globe temperature (WBGT) reference values in order to reduce heat strain in
      physical workers. The aim of this study was to develop MR prediction equation for
      younger and older men in hot working environments. METHODS: We measured the MR
      and heart rate (HR) of both younger and older men at ambient temperatures (Ta) of
      25, 30 and 35 degrees C while they cycled on a bicycle ergometer at a workload of
      30, 45 and 60% of maximal oxygen uptake (VO2max). Seven younger male university
      students aged 22.9 +/- 0.7 (mean +/- SD) years and seven older male workers aged
      61.7 +/- 2.2 (mean +/- SD) years participated in this study. MR, HR and rectal
      temperature (Tre) were measured during the study. HR, ambient temperature (Ta),
      body weight (BW) and body fat percentage (BF) served as predictors of MR using
      multivariate analysis. To increase the MR prediction accuracy, the following
      three alternative predictors of HR were used: HRres, calculated as 100 * [(HR -
      resting HR) / (maximal HR - resting HR)]; HRnet, calculated as (HR - resting HR);
      and HRi, calculated as (HR / resting HR). RESULTS: The R(2) value indicated that
      the models with HRres or HRnet were more accurate than those with HRi or HR. Ta
      had a significantly positive correlation with MR in older men. BW had a
      significantly positive correlation with MR in both younger and older men, and BF
      had a significantly negative correlation with MR in both younger and older men.
      CONCLUSIONS: HRres or HRnet enabled more accurate MR prediction than HR. BW and
      BF would increase the accuracy of MR prediction.

PMID- 25374420
TI  - Biological monitoring method for urinary neonicotinoid insecticides using LC
      MS/MS and its application to Japanese adults.
AB  - OBJECTIVES: Agricultural use of neonicotinoid (NEO) insecticides has been
      increasing in recent years, but their biological monitoring methods have been
      scarcely reported. In this study, we developed and validated a rapid and
      sensitive method for quantifying urinary NEO concentrations using high
      performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS:
      After phosphate-induced acidification of a urine sample, urinary NEOs were
      trapped by a solid-phase extraction column and eluted with methanol for
      acetamiprid, imidacloprid, thiacloprid, thiamethoxam, clothianidin and
      dinotefuran and with an acetonitrile and methanol solution (1:1, v/v) containing
      5% NH3 for nitenpyram. A separation analysis was performed by LC-MS/MS within 10
      minutes for the sample. This method was applied to first morning urine obtained
      from 52 Japanese (40.9 +/- 10.5 years old, mean +/- standard deviation) without
      occupational NEO exposure. RESULTS: The linear dynamic ranges and their limit of
      quantification (LOQ, signal to noise ratio=10) levels were 0.3-20 or 50 ug/l
      (r=0.998-0.999) and 0.05-0.36 ug/l, respectively. The absolute recovery was 64
      95%, and the intra- and inter-day precisions were less than 16.4% (relative
      standard deviation, %RSD). This method was successfully applied for analysis of
      NEOs in human urine samples obtained from 52 adults. The frequencies of
      individuals who showed more than LOD levels was above 90% for imidacloprid,
      thiamethoxam, clothianidin and dinotefuran, more than 50% for acetamiprid and
      thiacloprid and 29% for nitenpyram. CONCLUSIONS: These results indicated that our
      new method could be applied to biological monitoring of NEO exposure even at
      environmental exposure levels in Japanese adults without occupational spraying
      histories.

PMID- 25374421
TI  - Visual recognition memory test performance was improved in older adults by
      extending encoding time and repeating test trials.
AB  - OBJECTIVES: The aim of this study was to investigate whether the combination of
      extension of the encoding time and repetition of a test trial would improve the
      visual recognition memory performance in older adults. METHODS: We evaluated
      visual memory performance in young and older adults on a Yes-No recognition
      memory test under four different conditions. The conditions consisted of
      combinations of encoding times of two and four seconds (E2 and E4) and first and
      second retrieval practice test trials (T1 and T2): E2T1, E2T2, E4T1 and E4T2.
      Performance was evaluated by measuring hit rates, false alarm rates,
      discrimination ability and response bias. RESULTS: Older adults showed better
      improvement of hit rate and discrimination ability under the E4T2 conditions
      whereas young adults showed better memory performance under the E2T2 conditions.
      CONCLUSIONS: A longer encoding time and repetition of the test was effective in
      improving the visual memory performance in terms of the hit rates and
      discrimination ability of older adults. The results suggest that this strategy
      should be useful in providing a suitable work environment for older workers.

PMID- 25374422
TI  - Sex differences in factors contributing to family-to-work and work-to-family
      conflict in Japanese civil servants.
AB  - OBJECTIVES: As the number of dual-earner couples in Japan has increased, work
      life balance has become important. This study aimed to examine the factors that
      contribute to work-family conflict. METHODS: The participants included 3,594
      (2,332 men and 1,262 women) civil servants aged 20-59 working for local
      government on the west coast of Japan. Logistic regression analysis was used to
      evaluate whether work, family, or lifestyle characteristics were associated with
      work-family conflict. RESULTS: For men, family-to-work conflict was associated
      with being elderly, having low-grade employment, working long hours, raising
      children, and sleeping shorter hours. For women, being married and raising
      children were strong determinants of family-to-work conflict, and being middle
      aged, working long hours, and sleeping shorter hours were also associated with
      this type of conflict. Regarding work-to-family conflict, working long hours was
      the strongest determinant of conflict in both sexes. In men, being elderly,
      living with family, eating dinner late, and sleeping shorter hours were also
      associated with work-to-family conflict. In women, having high-grade employment,
      being married, raising children, and eating dinner late were associated with work
      to-family conflict. CONCLUSIONS: This study showed that working long hours was
      the primary determinant of work-to-family conflict in both sexes and that being
      married and raising children were strong factors of family-to-work conflict in
      women only. Sex differences may reflect divergence of the social and domestic
      roles of men and women in Japanese society. To improve the work-life balance,
      general and sex-specific health policies may be required.

PMID- 25374423
TI  - Medicalization and epistemic injustice.
AB  - Many critics of medicalization (the process by which phenomena become candidates
      for medical definition, explanation and treatment) express concern that the
      process privileges individualised, biologically grounded interpretations of
      medicalized phenomena, inhibiting understanding and communication of aspects of
      those phenomena that are less relevant to their biomedical modelling. I suggest
      that this line of critique views medicalization as a hermeneutical injustice--a
      form of epistemic injustice that prevents people having the hermeneutical
      resources available to interpret and communicate significant areas of their
      experience. Interpreting the critiques in this fashion shows they frequently fail
      because they: neglect the ways in which medicalization may not obscure, but
      rather illuminate, individuals' experiences; and neglect the testimony of those
      experiencing first-hand medicalized problems, thus may be guilty of perpetrating
      testimonial injustice. However, I suggest that such arguments are valuable
      insofar as they highlight the unwarranted epistemic privilege frequently afforded
      to medical institutions and medicalized models of phenomena, and a consequent
      need for greater epistemic humility on the part of health workers and
      researchers.

PMID- 25374424
TI  - Lattice dynamics in intermetallic Mg2Ge and Mg2Si.
AB  - The lattice dynamics of polycrystalline Mg(2)Ge and Mg(2)Si are compared using
      both microscopic and macroscopic measurements as well as theoretical
      calculations. The volume thermal expansion coefficient between 200 and 300 K was
      found to be 4.37(5) . 10(-5) K(-1) in Mg(2)Ge, compared to 3.69(5) . 10(-5) K(-1)
      in Mg(2)Si. Inelastic neutron scattering measurements yield densities of phonon
      states which are in line with theoretical calculations. The microscopic data were
      corroborated with macroscopic calorimetry measurements and provide quantified
      values for anharmonicity. The estimated macroscopic Gruneisen parameter is,
      gamma(Mg(2)Si) = 1.17(5) and gamma(Mg(2)Ge) = 1.46(5) at 295 K, in excellent
      agreement with Raman scattering data. Although the element specific mean force
      constants are practically the same, in Mg(2)Ge and Mg(2)Si, a mass homology
      relation alone cannot reproduce the difference in the partial densities of
      vibrational states in these compounds and differences in elemental bonding should
      be taken into account.

PMID- 25374426
TI  - An infectious molecular clone in early infection with HIV-1 subtype CRF01_AE
      strains: construction and biological properties.
AB  - Our aim was to construct infectious molecular clones of the CRF01_AE subtype in
      the primary infection phase of an acute HIV-1 infections in people screened from
      MSM populations, as well as continue preliminary research on this virus and its
      biological properties pertaining to deriving viruses. Walking sequencing was
      performed on a half-molecular clone with target fragment inserted. Western Blot
      was used to detect protein expression in HIV-1 infected 293T cells. Sequence
      analysis of HIV-1 genomic clones showed full-length HIV-1 genomic clones without
      frame shift mutation or termination codon. HIV-1 p24 antigens generated from 08
      IMC were slightly greater than those from infectious molecular clones pNL4-3 3
      and 93JP-NH1, but without statistical difference (all P > 0.05). The relative
      light units of 08-ISO was higher than those of 08-IMC, but no significant
      difference was observed (all P > 0.05). 08-IMC-driven virus was linked to lower
      replication kinetics. The replication levels of pNL4-3 and 08-ISO were
      significantly higher than the 08-IMC replication level but close to NH1
      replication level (all P < 0.05). 08-IMC could infect the cells expressing CCR5
      and be replicated in the CCR5-expressing cells with a positive percentage of 24.3
      %, 08-ISO may use CCR5-using macrophage-tropic isolates as coreceptor, while pNL4
      3 viruses with T cell tropisms utilize the CXCR4 co-receptor. Our study showed
      that the infectious molecular clones of viruses in the primary infection phase
      have a close relationship with the major prevalent CRF01_AE strains and have high
      homology with the viral RNA in plasma.

PMID- 25374427
TI  - Knockdown of filaggrin influences the epidermal terminal differentiation via MAPK
      pathway in normal human epidermal keratinocytes.
AB  - We aimed to gain further insight into the role of the MAPK signaling pathway in
      terminal differentiation of normal human epidermal keratinocytes (NHEKs) with
      filaggrin knockdown. Filaggrin expression was knocked down by shRNA technology
      and the MAPK pathways were inhibited by three different inhibitors in NHEKs. The
      associated mRNAs and proteins were investigated by RT-PCR and western blot.
      Filaggrin absence inhibited the expression of differentiation-associated
      proteins, and blocked the protein expression of p38 MAPK, ERK1/2, JNK, Akt and NF
      kappaB. Moreover, inhibited p38 MAPK, instead of ERK1/2 or JNK, lead to decreases
      in the expressions of Akt, NF-kappaB, and differentiation- associated proteins.
      In conclusion, Filaggrin might affect the epidermal terminal differentiation
      mainly through the p38-MAPK, NF-kappaB and Akt pathways. ERK1/2 and JNK might
      also be involved in the process.

PMID- 25374425
TI  - Implication of matrix metalloproteinases in regulating neuronal disorder.
AB  - Neurological disorder is an abnormal condition of the nervous system that occurs
      due to the structural and biochemical abnormalities of nerves in brain and spinal
      cord. The nervous system, once exposed, has a limited capacity of self-repair.
      Neurodegeneration refers to the phenomenon of the structural and functional loss
      of neurons and the rate of which is accelerated by aging. Recent studies
      identified the blood brain barrier as hotspot of damage due to neurodegeneration.
      Depending on the location and severity of damage, the neurons succumb to death
      through the apoptotic, autophagic and necrotic pathways. The neurological system
      reorients the structure of neuronal circuits in order to maintain the neuronal
      plasticity during neurological disorders like Alzheimer's disease, Parkinson's
      disease, Huntington's disease, multiple sclerosis etc. Matrix metalloproteinases
      (MMPs), a family of Zn(2+) dependent endopeptidases play an important role in
      those neurodegenerative disorders. Recent studies implicated the role of MMPs in
      acute neuroinflammatory damage as well as in chronic neurodegeneration. The
      critical function of individual MMPs in tissue repair is also very important.
      MMPs serve important functions in the central nervous system (CNS) during growth
      and development. Besides, MMPs are important in neuronal damage in acute and
      chronic conditions as well as repair processes. Studies reveal that MMPs and the
      tissue inhibitors of metalloproteinases (TIMPs) play pivotal roles in
      pathogenesis and recovery of neurons. The expression and activities of MMPs are
      regulated by signaling molecules, TIMPs, cell surface receptors and transcription
      factors. In this review, we attempt to elucidate the role of MMPs in
      neurodegeneration and their functional mechanism in repairing the CNS. We also
      provide information for the therapeutics in neuronal disorder in the perspective
      of MMP regulation.

PMID- 25374428
TI  - Interleukin-18 gene promoter polymorphisms and celiac disease in Italian
      patients.
AB  - Celiac disease (CD) is the most common food-sensitive enteropathy in genetically
      susceptible individuals. The major genetic risk factors known are specific human
      leukocyte antigen (HLA)-DQ haplotypes, but other genetic factors are supposed to
      be involved. Interleukin-18 (IL-18) is a pro-inflammatory cytokine that has an
      important role in the immune defense and it has the potential to influence
      inflammatory disorders. IL-18 is able to promote Th1 cell development and it is
      expressed in the mucosa of the small intestine in celiac patients. Given the IL
      18 biological role, and since a few studies have previously suggested its
      involvement in CD, in order to investigate the role of IL18 gene in the
      susceptibility to CD we have performed a case-control study, analyzing two IL18
      gene promoter polymorphisms, previously reported to impair the transcriptional
      activity of the gene, (-137G > C and -607C > A, rs187238 and rs1946518
      respectively). A total of 556 CD Italian patients and 582 controls, further
      stratified for HLA class II (DQ) CD risk haplotypes were enrolled. The -607A > C
      A allele and A/A genotype, as well as the combination of this allele with the 
      137G allele in the AG haplotype, were associated with an increased risk towards
      CD development, in particular in HLA-DQ2.2 patients. Although the association was
      very moderate, our results indicate the possible involvement of IL18 gene in the
      susceptibility to CD, and for this reason we do think it should deserve further
      investigation.

PMID- 25374429
TI  - Serotonin transporter polymorphism (5-HTTLPR) in Croatian population.
AB  - Serotonin transporter polymorphism (5-HTTLPR) is a well-studied polymorphism in
      psychiatric research. The function of serotonin transporter is to control neural
      stimulation and maintain homeostasis of serotonin in other cells like platelets
      and enterochromaffin cells. Considering serotonin function in human behavior, and
      the role of serotonin transporter, 5-HTTLPR has been associated with depression
      related disorders, anxiety related personality traits, and adverse response to
      psychotherapy. However, many studies failed to replicate the association of 5
      HTTLPR polymorphism with mentioned disorders. The aim of our study was to assess
      genotype frequencies in Croatian physically and psychologically healthy
      population and compare our results with previously published data. Genotype
      distribution in our research was similar to previous studies on Caucasian
      population regardless of inclusion criteria. Genotype distribution was as
      follows: LL 38 %; LS 45 %; SS 17 % and allele frequencies for L and S allele were
      61 and 39 %, respectively. Obtained results were in an agreement with the Hardy
      Weinberg equilibrium. Comparing inclusion criteria from different studies, we
      noticed a difference in population selection from one study to another. Increased
      possibility for selection bias, population stratification and complexity of
      psychiatric disorders might present a source of possible errors in genetic
      association studies.

PMID- 25374431
TI  - Importance of HPV Genotyping for the Screening, Therapy and Management of
      Cervical Neoplasias.
AB  - In the last decade, the detection of human papillomaviruses (HPV) has become
      increasingly important in cervical cancer screening and the treatment of cancer
      precursors. HPV screening is recommended for the further evaluation of abnormal
      Pap tests or during follow-up after treating precancerous lesions. Several
      randomised controlled studies have shown that screening for cervical cancer using
      HPV detection can be more effective than cytology alone. Genotyping of different
      high-risk HPV (hrHPV) types obtained from smear tests has not yet gained
      widespread acceptance in clinical practice. However, significant differences have
      been noted in the oncogenicity of hrHPV genotypes. HPV 16 is by far the most
      common and oncogenic genotype. Genotyping of hrHPV could be helpful for the risk
      stratification of HPV-positive women.

PMID- 25374430
TI  - Oncolytic Viruses to Treat Ovarian Cancer Patients - a Review of Results From
      Clinical Trials.
AB  - Oncolytic viruses are replication competent "live" viruses. They infect tumor
      cells, replicate highly selective inside and thereby destroy them. Because of the
      enormous advances in the field of genetic engineering and biotechnology during
      the last decade, virotherapy is increasingly used within clinical trials and
      proved to be safe and effective. In particular, treatment of ovarian cancer
      patients is one main focus of research. On the one hand, this is due to the poor
      prognosis of this dismal entity, resulting in the urgent need for novel
      therapeutics. On the other hand, as ovarian cancer typically spreads within the
      peritoneal cavity, intraperitoneal administration of oncolytic viruses is
      feasible. This paper provides an overview of promising results from clinical
      trials to treat ovarian cancer patients with oncolytic viruses.

PMID- 25374432
TI  - Reprogrammed Astrocytes as a Potential Therapy for Neurodegenerative Disorders.

PMID- 25374433
TI  - Importance of follow-up cerebrospinal fluid analysis in cryptococcal
      meningoencephalitis.
AB  - Cryptococcal meningoencephalitis represents a serious infection of the central
      nervous system, where reliable prognostic factors during the disease course are
      needed. Twenty-one patients diagnosed with cryptococcal meningoencephalitis in a
      German university hospital from 1999 to 2013 were analysed retrospectively. CSF
      parameters were analysed prior to therapy and during antifungal treatment and
      were compared between patients who survived or deceased. Fifteen patients
      clinically improved after antifungal therapy, while six patients died. No
      differences were observed between the outcome groups for the CSF parameters cell
      count, lactate, total protein, and CSF-serum albumin quotients (QAlb). Follow-up
      examinations of serum cryptococcal antigen titer and CSF cell count have shown
      that these parameters cannot be used to monitor the efficacy of antifungal
      therapy as well. In contrast, the course of QAlb during therapy was indicative
      for the outcome as a possible prognostic marker. In patients with clinical
      improvement QAlb values were falling under therapy, while rising QAlb values were
      found in patients with fatal outcome indicating a continuing dysfunction of the
      blood-CSF barrier. In conclusion, our results indicate that, among the various
      CSF parameters, the course of QAlb presents a promising marker that might be used
      to monitor the efficacy of antifungal therapy. 

PMID- 25374434
TI  - System accuracy evaluation of the GlucoRx nexus voice TD-4280 blood glucose
      monitoring system.
AB  - Use of blood glucose (BG) meters in the self-monitoring of blood glucose (SMBG)
      significantly lowers the risk of diabetic complications. With several BG meters
      now commercially available, the International Organization for Standardization
      (ISO) ensures that each BG meter conforms to a set degree of accuracy. Although
      adherence to ISO guidelines is a prerequisite for commercialization in Europe,
      several BG meters claim to meet the ISO guidelines yet fail to do so on internal
      validation. We conducted a study to determine whether the accuracy of the GlucoRx
      Nexus TD-4280 meter, utilized by our department for its cost-effectiveness,
      complied with ISO guidelines. 105 patients requiring laboratory blood glucose
      analysis were randomly selected and reference measurements were determined by the
      UniCel DxC 800 clinical system. Overall the BG meter failed to adhere to the
      >=95% accuracy criterion required by both the 15197:2003 (overall accuracy 92.4%)
      and 15197:2013 protocol (overall accuracy 86.7%). Inaccurate meters have an
      inherent risk of over- and/or underestimating the true BG concentration, thereby
      risking patients to incorrect therapeutic interventions. Our study demonstrates
      the importance of internally validating the accuracy of BG meters to ensure that
      its accuracy is accepted by standardized guidelines. 

PMID- 25374435
TI  - Engineering biodegradable nanoparticles for drug and gene delivery.

PMID- 25374436
TI  - Who Owns the Intellectual Property Rights to Chinese Genetically Modified Rice?
      Evidence from Patent Portfolio Analysis.

PMID- 25374437
TI  - Comparison of Anxiolytic Effects of Acute Exercise in Older Versus Younger
      Adults.
AB  - Although the anxiolytic effect of acute exercise is well established, there is
      little understanding regarding whether this effect differs across age. The
      purpose of this investigation was to compare anxiolytic effects of acute exercise
      in older versus younger volunteers. Older (n = 32, aged 59-75 years) and younger
      (n = 45, aged 18-30 years), aerobically fit volunteers were assessed. On 3
      consecutive days, participants ran/walked for 60 min at 65% to 75% of heart-rate
      reserve. The Spielberger State-Trait Anxiety Inventory (Form Y1) was administered
      5 min before and 20 min after each exercise bout. Mean state anxiety before and
      after exercise was analyzed by repeated measures age-by-gender-by-time ANOVA. A
      significantly greater anxiolytic effect of exercise in the older versus younger
      participants was found for the mean data (p < .001), as well as each of the 3
      individual days. The results suggest greater anxiolytic effects of vigorous acute
      exercise in older compared to younger adults.

PMID- 25374438
TI  - Female College Drinking and the Social Learning Theory: An Examination of the
      Developmental Transition Period from High School to College.
AB  - Problematic drinking among college students remains a national issue with large
      percentages of college students reporting heavy episodic or binge drinking
      (Wechsler, Dowdall, Davenport, & Castillo, 1995) and experiencing severe alcohol
      related consequences ranging from poor academic performance, to sexual assault,
      vandalism, and even death (Hingson, Heeren, Winter, & Wechsler, 2005; Wechsler et
      al., 2002). According to the National Institute on Alcohol Abuse and Alcoholism
      (NIAAA, 2002), the first 6 weeks on a college campus are critical to first-year
      student success. However, during these first weeks many students initiate heavy
      drinking that may interfere with their ability to adapt to campus life, and
      patterns of drinking established during these first weeks persist throughout
      college (Schulenberg et al., 2001). Approximately one third of first-year
      students fail to enroll for their second year due to difficulties with the
      transition to college (Upcraft, 1995). Drinking may compromise successful
      negotiation of the transition into college and therefore jeopardize overall
      collegiate success. Therefore, the ability to identify specific students as they
      enter college who may develop problematic drinking patterns and related negative
      consequences would allow student affairs personnel to more effectively design and
      target risk-reduction programs and interventions.

PMID- 25374439
TI  - Type 1 diabetes and autoimmunity.
AB  - Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the
      autoimmune response against pancreatic beta cells. T1D is often complicated with
      other autoimmune diseases, and anti-islet autoantibodies precede the clinical
      onset of disease. The most common coexisting organ-specific autoimmune disease in
      patients with T1D is autoimmune thyroid disease, and its frequency is estimated
      at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti
      thyroid antibodies in children with T1D at disease onset is about 20% and is
      particularly common in girls. Furthermore, patients with anti-thyroid antibodies
      are 18 times more likely to develop thyroid disease than patients without anti
      thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease
      in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset
      and in yearly intervals after the age of 12 yr is recommended. Anti-islet
      autoantibodies are predictive and diagnostic markers for T1D. The most frequently
      detected autoantibodies in Japanese patients are GAD autoantibodies (~80%)
      followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8
      autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D
      can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8
      and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it
      is important to develop a diagnostic strategy for patients with type 1A diabetes
      in consideration of the age or mode of disease onset. 

PMID- 25374440
TI  - Increased Secretion of Endogenous GH after Treatment with an Intranasal GH
      releasing Peptide-2 Spray Does Not Promote Growth in Short Children with GH
      Deficiency.
AB  - We investigated whether treatment with an intranasal GH-releasing peptide (GHRP)
      2 spray, which acts as a potent GH secretagogue that stimulates endogenous GH
      secretion, promotes growth in patients with GH deficiency (GHD). This study
      involved 126 prepubertal short children (81 males, 45 females) with a height SD
      score of -2 SD or less, who had been diagnosed as having GHD based on GH
      stimulation tests, and in whom the serum GH concentrations increased up to 9
      ng/ml after preliminary administration of an intranasal GHRP-2 spray. The
      subjects included in this study were divided into 3 groups by use of a double
      blind method; that is 44 were placed into the placebo group (P group: 30 males,
      14 females), 41 were placed into the GHRP-2 low dose group (L group: 25 males, 16
      females), and 41 were placed into the GHRP-2 high dose group (H group: 26 males,
      15 females). Those with a body wt of less than 20 kg were administered a placebo
      (P group), 50 MUg of GHRP-2 (L group) or 100 MUg of GHRP-2 (H group), and those
      with a body wt of 20 kg or more were administered a placebo (P group), 100 ug of
      GHRP-2 (L group) or 200 ug of GHRP-2 (H group) twice daily (morning and evening)
      for 48 continuous wk. Age and height SD scores at baseline were not significantly
      different among the three groups: 7.5 yr old and -2.26 SD in the P group, 7.3 yr
      old and -2.38 SD in the L group, and 7.5 yr old and -2.27 SD in the H group. Of
      the 126 subjects, 44, 40 and 40 subjects in the P, L and H groups, respectively,
      completed the 48 continuous wk of treatment. The changes in the mean height SD
      scores (mean growth rate) after 48 wk of treatment in the P, L and H groups were
      0.07 SD, 0.03 SD, and 0.02 SD, respectively, and thus no significant differences
      was observed among the 3 groups. Also no significant changes in blood IGF-I
      levels at baseline or after 48 wk of treatment were observed among the 3 groups.
      This study revealed that in patients with GHD, an increase in endogenous GH
      secretion as a result of treatment with GHRP-2 does not promote growth. It is
      speculated that the area under the curve of serum GH concentration by GHRP-2
      spray is too small to produce biological effects. In conclusion, it was
      demonstrated that growth cannot be promoted by a transient increase in endogenous
      GH secretion. 

PMID- 25374441
TI  - A novel deletion mutation of the arginine vasopressin receptor 2 gene in a
      Japanese infant with nephrogenic diabetes insipidus.

PMID- 25374442
TI  - Immune activation, immunosenescence, and osteoprotegerin as markers of
      endothelial dysfunction in subclinical HIV-associated atherosclerosis.
AB  - HIV-infected patients have a significantly greater risk of cardiovascular
      disease. Several markers including osteoprotegerin have been shown to be involved
      in the development and progression of atherosclerosis. We investigated the
      relationship between T-cell phenotype, osteoprotegerin, and atherosclerosis
      evaluated by carotid intima-media thickness (c-IMT) in 94 HIV+ patients on
      suppressive antiretroviral therapy with Framingham score <10%. As for the control
      group, 24 HIV-negative subjects were enrolled. c-IMT was assessed by ultrasound.
      CD4+/CD8+ T-cell activation (CD38+ HLADR+) and senescence (CD57+ CD28-) were
      measured by flow cytometry. IL-6 and OPG levels were measured by ELISA kit. c-IMT
      was higher in HIV+ than in controls. Among HIV+ patients, 44.7% had pathological
      c-IMT (>=0.9 mm). CD8+ T-cell activation and senescence and OPG plasma levels
      were higher in HIV+ patients than in controls. Subjects with pathological c-IMT
      exhibited higher CD8+ immune activation and immunosenescence and OPG levels than
      subjects with normal c-IMT. Multivariate analysis showed that age, CD8+ CD38+
      HLADR+, and CD8+ CD28- CD57+ were independently associated with pathological c
      IMT. Several factors have been implicated in the pathogenesis of atherosclerosis
      in HIV patients. Immune activation and immunosenescence of CD8+ T cell together
      with OPG plasma levels might be associated with the development and progression
      of early atherosclerosis, even in the case of viral suppression.

PMID- 25374443
TI  - A natural flavonoid glucoside, icariin, regulates Th17 and alleviates rheumatoid
      arthritis in a murine model.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that
      causes deformity of the joints and physical disability. Icariin, a natural
      flavonoid glucoside isolated from plants in the Epimedium family, has been proven
      to have various pharmacological activities. A recent study showed that icariin
      suppressed cartilage and bone degradation in mice of collagen-induced arthritis.
      However, the mechanism needs to be further investigated. In our current study, we
      found that icariin reduced the arthritis score and the incidence of arthritis
      compared with that in mice treated with water. Icariin inhibits the expression of
      various osteoclastogenic markers, such as beta3 integrin, cathepsin K, and MMP9
      in vitro. Icariin treatment in mice with CIA also resulted in less number of Th17
      cells and decreased ratio of CD4(+)IL-17(+) cells. The alleviated arthritis score
      and incidence of arthritis and reduced serum levels of IgG2a induced by icariin
      were abolished with additional IL-17 administration. Furthermore, icariin
      inhibited STAT3 activation in T cells and STAT3 inhibitor resulted in decreased
      IL-17 production and alleviated RA. In conclusion, icariin decreases Th17 cells
      and suppresses the production of IL-17, which contributes to the alleviated
      rheumatoid arthritis, through the inhibition of STAT3 activation. 

PMID- 25374444
TI  - Cardiac fibroblasts aggravate viral myocarditis: cell specific coxsackievirus B3
      replication.
AB  - Myocarditis is an inflammatory disease caused by viral infection. Different
      subpopulations of leukocytes enter the cardiac tissue and lead to severe cardiac
      inflammation associated with myocyte loss and remodeling. Here, we study possible
      cell sources for viral replication using three compartments of the heart:
      fibroblasts, cardiomyocytes, and macrophages. We infected C57BL/6j mice with
      Coxsackievirus B3 (CVB3) and detected increased gene expression of anti
      inflammatory and antiviral cytokines in the heart. Subsequently, we infected
      cardiac fibroblasts, cardiomyocytes, and macrophages with CVB3. Due to viral
      infection, the expression of TNF-alpha, IL-6, MCP-1, and IFN-beta was
      significantly increased in cardiac fibroblasts compared to cardiomyocytes or
      macrophages. We found that in addition to cardiomyocytes cardiac fibroblasts were
      infected by CVB3 and displayed a higher virus replication (132-fold increase)
      compared to cardiomyocytes (14-fold increase) between 6 and 24 hours after
      infection. At higher virus concentrations, macrophages are able to reduce the
      viral copy number. At low virus concentration a persistent virus infection was
      determined. Therefore, we suggest that cardiac fibroblasts play an important role
      in the pathology of CVB3-induced myocarditis and are another important
      contributor of virus replication aggravating myocarditis. 

PMID- 25374446
TI  - A3 adenosine receptor allosteric modulator induces an anti-inflammatory effect:
      in vivo studies and molecular mechanism of action.
AB  - The A3 adenosine receptor (A3AR) is overexpressed in inflammatory cells and in
      the peripheral blood mononuclear cells of individuals with inflammatory
      conditions. Agonists to the A3AR are known to induce specific anti-inflammatory
      effects upon chronic treatment. LUF6000 is an allosteric compound known to
      modulate the A3AR and render the endogenous ligand adenosine to bind to the
      receptor with higher affinity. The advantage of allosteric modulators is their
      capability to target specifically areas where adenosine levels are increased such
      as inflammatory and tumor sites, whereas normal body cells and tissues are
      refractory to the allosteric modulators due to low adenosine levels. LUF6000
      administration induced anti-inflammatory effect in 3 experimental animal models
      of rat adjuvant induced arthritis, monoiodoacetate induced osteoarthritis, and
      concanavalin A induced liver inflammation in mice. The molecular mechanism of
      action points to deregulation of signaling proteins including PI3K, IKK, IkappaB,
      Jak-2, and STAT-1, resulting in decreased levels of NF-kappaB, known to mediate
      inflammatory effects. Moreover, LUF6000 induced a slight stimulatory effect on
      the number of normal white blood cells and neutrophils. The anti-inflammatory
      effect of LUF6000, mechanism of action, and the differential effects on
      inflammatory and normal cells position this allosteric modulator as an attractive
      and unique drug candidate. 

PMID- 25374445
TI  - Diethylcarbamazine reduces chronic inflammation and fibrosis in carbon
      tetrachloride- (CCl4-) induced liver injury in mice.
AB  - This study investigated the anti-inflammatory effects of DEC on the CCl4-induced
      hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p.
      administration of CCl4 0.5 MUL/g of body weight through two injections a week for
      6 weeks. DEC (50 mg/kg) was administered by gavage for 12 days before finishing
      the CCl4 induction. Histological analyses of the DEC-treated group exhibited
      reduced inflammatory process and prevented liver necrosis and fibrosis.
      Immunohistochemical and immunofluorescence analyses of the DEC-treated group
      showed reduced COX-2, IL1beta, MDA, TGF-beta, and alphaSMA immunopositivity,
      besides exhibiting decreased IL1beta, COX-2, NFkappaB, IFNgamma, and TGFbeta
      expressions in the western blot analysis. The DEC group enhanced significantly
      the IL-10 expression. The reduction of hepatic injury in the DEC-treated group
      was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results
      of the present study, DEC can be used as a potential anti-inflammatory drug for
      chronic hepatic inflammation.

PMID- 25374448
TI  - TRIFUNCTIONAL LIGANDS: A RADIOIODINATED HIGH AFFINITY ACYLATING ANTAGONIST FOR
      THE A1 ADENOSINE RECEPTOR.
AB  - A new xanthine (adenosine antagonist) radioligand that binds covalently to A1
      adenosine receptors was prepared and used as a receptor probe. BH-DITC-XAC was
      synthesized via a trifunctional aryl diisothiocyanate crosslinker. containing the
      p-hydroxyphenylpropionyl group for radioiodination. The xanthine competed against
      agonist or antagonist A1 receptor radioligands in bovine brain membranes with an
      IC50, of 40nM. 125I-BH-DITC-XAC, prepared directly by the chloramine T method and
      purified by HPLC. bound specifically to A1 receptors. This binding was inhibited
      in the presence of the adenosine agonists R-PIA, S-PIA. and NECA in a dose
      dependent manner and with the order of potency characteristic of bovine A1
      receptors. Incubation of affinity purified bovine A1-receptors with 125I-BH-DITC
      XAC (0.8 nM) for 2 hours resulted in the specific and clean labelling of a
      polypeptide band corresponding to MW 36,000, identical to that previously found
      for the A1 receptor.

PMID- 25374447
TI  - LPS from P. gingivalis and hypoxia increases oxidative stress in periodontal
      ligament fibroblasts and contributes to periodontitis.
AB  - Oxidative stress is characterized by an accumulation of reactive oxygen species
      (ROS) and plays a key role in the progression of inflammatory diseases. We
      hypothesize that hypoxic and inflammatory events induce oxidative stress in the
      periodontal ligament (PDL) by activating NOX4. Human primary PDL fibroblasts were
      stimulated with lipopolysaccharide from Porphyromonas gingivalis (LPS-PG), a
      periodontal pathogen bacterium under normoxic and hypoxic conditions. By
      quantitative PCR, immunoblot, immunostaining, and a specific ROS assay we
      determined the amount of NOX4, ROS, and several redox systems. Healthy and
      inflamed periodontal tissues were collected to evaluate NOX4 and redox systems by
      immunohistochemistry. We found significantly increased NOX4 levels after hypoxic
      or inflammatory stimulation in PDL cells (P < 0.001) which was even more
      pronounced after combination of the stimuli. This was accompanied by a
      significant upregulation of ROS and catalase (P < 0.001). However, prolonged
      incubation with both stimuli induced a reduction of catalase indicating a
      collapse of the protective machinery favoring ROS increase and the progression of
      inflammatory oral diseases. Analysis of inflamed tissues confirmed our
      hypothesis. In conclusion, we demonstrated that the interplay of NOX4 and redox
      systems is crucial for ROS formation which plays a pivotal role during oral
      diseases. 

PMID- 25374449
TI  - Predictors of Positive Outcomes in Offspring of Depressed Parents and Non
      depressed Parents Across 20 Years.
AB  - Understanding differences in factors leading to positive outcomes in high-risk
      and low-risk offspring has important implications for preventive interventions.
      We identified variables predicting positive outcomes in a cohort of 235 offspring
      from 76 families in which one, both, or neither parent had major depressive
      disorder. Positive outcomes were termed resilient in offspring of depressed
      parents, and competent in offspring of non-depressed parents, and defined by two
      separate criteria: absence of psychiatric diagnosis and consistently high
      functioning at 2, 10, and 20 years follow-up. In offspring of depressed parents,
      easier temperament and higher self-esteem were associated with greater odds of
      resilient outcome defined by absence of diagnosis. Lower maternal overprotection,
      greater offspring self-esteem, and higher IQ were associated with greater odds of
      resilient outcome defined by consistently high functioning. Multivariate analysis
      indicated that resilient outcome defined by absence of diagnosis was best
      predicted by offspring self-esteem; resilient outcome defined by functioning was
      best predicted by maternal overprotection and self-esteem. Among offspring of non
      depressed parents, greater family cohesion, easier temperament and higher self
      esteem were associated with greater odds of offspring competent outcome defined
      by absence of diagnosis. Higher maternal affection and greater offspring self
      esteem were associated with greater odds of competent outcome, defined by
      consistently high functioning. Multivariate analysis for each criterion indicated
      that competent outcome was best predicted by offspring self-esteem. As the most
      robust predictor of positive outcomes in offspring of depressed and non-depressed
      parents, self-esteem is an important target for youth preventive interventions.

PMID- 25374450
TI  - Comparative Study on Sequence-Structure-Function Relationship of the Human Short
      chain Dehydrogenases/Reductases Protein Family.
AB  - Human short-chain dehydrogenases/reductases (SDRs) protein family has been the
      subject of recent studies for its critical role in human metabolism. Studies also
      found that single nucleotide polymorphisms of the SDR protein family were
      responsible for a variety of genetic diseases, including type II diabetes. This
      study reports the effect of sequence variation on the structural and functional
      integrities of human SDR protein family using phylogenetics and correlated
      mutation analysis tools. Our results indicated that (i) tyrosine, serine, and
      lysine are signature protein residues that have direct contribution to the
      structural and functional stabilities of the SDR protein family, (ii) subgroups
      of SDR protein family have their own signature protein combination that represent
      their unique functionality, and (iii) mutations of the human SDR protein family
      showed high correlation in terms of evolutionary history. In combination, the
      results inferred that over evolutionary history, the SDR protein family was able
      to diverge itself in order to adapt with the changes in human nutritional
      demands. Our study reveals understanding of structural and functional scaffolds
      of specific SDR subgroups that may facilitate the design of specific inhibitor. 

PMID- 25374451
TI  - Cloning and Expression Profiling of the Polycomb Gene, Retinoblastoma-related
      Protein from Tomato Solanum lycopersicum L.
AB  - Cell cycle regulation mechanisms appear to be conserved throughout eukaryotic
      evolution. One of the important proteins involved in the regulation of cell cycle
      processes is retinoblastoma-related protein (RBR), which is a negative regulator
      of cell cycle progression, controlling the G1/S transition in plants and animals.
      In this study, we present the cloning and genomic structure of a putative SlRBR
      gene in the tomato Solanum lycopersicum L. by isolating cDNA clones that
      correspond to the SlRBR gene from tomato using primers that were designed from
      available Solanaceae ESTs based on conserved sequences between the PcG genes in
      Arabidopsis thaliana and tomato. The SlRBR cDNAs were cloned into the pBS plasmid
      and sequenced. Both 5'- and 3'-RACE were generated and sequenced. FlcDNA of the
      SlRBR gene of 3,554 bp was composed of a 5'-UTR of 140 bp, an ORF of 3,054 bp,
      and a 3'-UTR of 360 bp. The translated ORF encodes a polypeptide of 1,018 amino
      acids. An alignment of the deduced amino acids indicates that there are highly
      conserved regions between the tomato SlRBR predicted protein and plant
      hypothetical RBR gene family members. Both of the unrooted phylogenetic trees,
      which were constructed using maximum parsimony and maximum likelihood methods,
      indicate a close relationship between the SlRBR predicted protein and the RBR
      protein of Nicotiana benthamiana. QRT-PCR indicates that SlRBR gene is expressed
      in closed floral bud tissues 1.7 times higher than in flower tissues, whereas the
      expression level in unripe fruit tissue is lower by about three times than in
      flower tissues. 

PMID- 25374452
TI  - CSNK1A1 and Gli2 as Novel Targets Identified Through an Integrative Analysis of
      Gene Expression Data, Protein-Protein Interaction and Pathways Networks in
      Glioblastoma Tumors: Can These Two Be Antagonistic Proteins?
AB  - Glioblastoma (GBM) is the malignant form of glioma, and the interplay of
      different pathways working in concert in GBM development and progression needs to
      be fully understood. Wnt signaling and sonic hedgehog (SHH) signaling pathways,
      having basic similarities, are among the major pathways aberrantly activated in
      GBM, and hence, need to be targeted. It becomes imperative, therefore, to explore
      the functioning of these pathways in context of each other in GBM. An integrative
      approach may help provide new biological insights, as well as solve the problem
      of identifying common drug targets for simultaneous targeting of these pathways.
      The beauty of this approach is that it can recapitulate several known facts, as
      well as decipher new emerging patterns, identifying those targets that could be
      missed when relying on one type of data at a time. This approach can be easily
      extended to other systems to discover key patterns in the functioning of
      signaling molecules. Studies were designed to assess the relationship between
      significant differential expression of genes of the Wnt (Wnt/beta-catenin
      canonical and Wnt non-canonical) and SHH signaling pathways and their
      connectivity patterns in interaction and signaling networks. Further, the aim was
      to decipher underlying mechanistic patterns that may be involved in a more
      specific way and to generate a ranked list of genes that can be used as markers
      or drug targets. These studies predict that Wnt pathway plays a relatively more
      pro-active role than the SHH pathway in GBM. Further, CTNNB1, CSNK1A1, and Gli2
      proteins may act as key drug targets common to these pathways. While CTNNB1 is a
      widely studied molecule in the context of GBM, the likely roles of CSNK1A1 and
      Gli2 are found to be relatively novel. It is surmised that Gli2 may be
      antagonistic to CSNK1A1, preventing the phosphorylation of CTNNB1 and SMO
      proteins in Wnt and SHH signaling pathway, respectively, by CSNK1A1, and thereby,
      aberrant activation. New insights into the possible behavior of these pathway
      molecules relative to each other in GBM reveal some key interesting patterns. 

PMID- 25374453
TI  - A comprehensive comparison of normalization methods for loading control and
      variance stabilization of reverse-phase protein array data.
AB  - Loading control (LC) and variance stabilization of reverse-phase protein array
      (RPPA) data have been challenging mainly due to the small number of proteins in
      an experiment and the lack of reliable inherent control markers. In this study,
      we compare eight different normalization methods for LC and variance
      stabilization. The invariant marker set concept was first applied to the
      normalization of high-throughput gene expression data. A set of "invariant"
      markers are selected to create a virtual reference sample. Then all the samples
      are normalized to the virtual reference. We propose a variant of this method in
      the context of RPPA data normalization and compare it with seven other
      normalization methods previously reported in the literature. The invariant marker
      set method performs well with respect to LC, variance stabilization and
      association with the immunohistochemistry/florescence in situ hybridization data
      for three key markers in breast tumor samples, while the other methods have
      inferior performance. The proposed method is a promising approach for improving
      the quality of RPPA data. 

PMID- 25374454
TI  - Classification of images acquired with colposcopy using artificial neural
      networks.
AB  - OBJECTIVE: To explore the advantages of using artificial neural networks (ANNs)
      to recognize patterns in colposcopy to classify images in colposcopy. PURPOSE:
      Transversal, descriptive, and analytical study of a quantitative approach with an
      emphasis on diagnosis. The training test e validation set was composed of images
      collected from patients who underwent colposcopy. These images were provided by a
      gynecology clinic located in the city of Criciuma (Brazil). The image database (n
      = 170) was divided; 48 images were used for the training process, 58 images were
      used for the tests, and 64 images were used for the validation. A hybrid neural
      network based on Kohonen self-organizing maps and multilayer perceptron (MLP)
      networks was used. RESULTS: After 126 cycles, the validation was performed. The
      best results reached an accuracy of 72.15%, a sensibility of 69.78%, and a
      specificity of 68%. CONCLUSION: Although the preliminary results still exhibit an
      average efficiency, the present approach is an innovative and promising technique
      that should be deeply explored in the context of the present study.

PMID- 25374455
TI  - eMBI: Boosting Gene Expression-based Clustering for Cancer Subtypes.
AB  - Identifying clinically relevant subtypes of a cancer using gene expression data
      is a challenging and important problem in medicine, and is a necessary premise to
      provide specific and efficient treatments for patients of different subtypes.
      Matrix factorization provides a solution by finding checker-board patterns in the
      matrices of gene expression data. In the context of gene expression profiles of
      cancer patients, these checkerboard patterns correspond to genes that are up- or
      down-regulated in patients with particular cancer subtypes. Recently, a new
      matrix factorization framework for biclustering called Maximum Block Improvement
      (MBI) is proposed; however, it still suffers several problems when applied to
      cancer gene expression data analysis. In this study, we developed many effective
      strategies to improve MBI and designed a new program called enhanced MBI (eMBI),
      which is more effective and efficient to identify cancer subtypes. Our tests on
      several gene expression profiling datasets of cancer patients consistently
      indicate that eMBI achieves significant improvements in comparison with MBI, in
      terms of cancer subtype prediction accuracy, robustness, and running time. In
      addition, the performance of eMBI is much better than another widely used matrix
      factorization method called nonnegative matrix factorization (NMF) and the method
      of hierarchical clustering, which is often the first choice of clinical analysts
      in practice. 

PMID- 25374457
TI  - RNAseqPS: A Web Tool for Estimating Sample Size and Power for RNAseq Experiment.
AB  - Sample size and power determination is the first step in the experimental design
      of a successful study. Sample size and power calculation is required for
      applications for National Institutes of Health (NIH) funding. Sample size and
      power calculation is well established for traditional biological studies such as
      mouse model, genome wide association study (GWAS), and microarray studies. Recent
      developments in high-throughput sequencing technology have allowed RNAseq to
      replace microarray as the technology of choice for high-throughput gene
      expression profiling. However, the sample size and power analysis of RNAseq
      technology is an underdeveloped area. Here, we present RNAseqPS, an advanced
      online RNAseq power and sample size calculation tool based on the Poisson and
      negative binomial distributions. RNAseqPS was built using the Shiny package in R.
      It provides an interactive graphical user interface that allows the users to
      easily conduct sample size and power analysis for RNAseq experimental design.
      RNAseqPS can be accessed directly at
      http://cqs.mc.vanderbilt.edu/shiny/RNAseqPS/. 

PMID- 25374456
TI  - A pan-cancer modular regulatory network analysis to identify common and cancer
      specific network components.
AB  - Many human diseases including cancer are the result of perturbations to
      transcriptional regulatory networks that control context-specific expression of
      genes. A comparative approach across multiple cancer types is a powerful approach
      to illuminate the common and specific network features of this family of
      diseases. Recent efforts from The Cancer Genome Atlas (TCGA) have generated large
      collections of functional genomic data sets for multiple types of cancers. An
      emerging challenge is to devise computational approaches that systematically
      compare these genomic data sets across different cancer types that identify
      common and cancer-specific network components. We present a module- and network
      based characterization of transcriptional patterns in six different cancers being
      studied in TCGA: breast, colon, rectal, kidney, ovarian, and endometrial. Our
      approach uses a recently developed regulatory network reconstruction algorithm,
      modular regulatory network learning with per gene information (MERLIN), within a
      stability selection framework to predict regulators for individual genes and gene
      modules. Our module-based analysis identifies a common theme of immune system
      processes in each cancer study, with modules statistically enriched for immune
      response processes as well as targets of key immune response regulators from the
      interferon regulatory factor (IRF) and signal transducer and activator of
      transcription (STAT) families. Comparison of the inferred regulatory networks
      from each cancer type identified a core regulatory network that included genes
      involved in chromatin remodeling, cell cycle, and immune response. Regulatory
      network hubs included genes with known roles in specific cancer types as well as
      genes with potentially novel roles in different cancer types. Overall, our
      integrated module and network analysis recapitulated known themes in cancer
      biology and additionally revealed novel regulatory hubs that suggest a complex
      interplay of immune response, cell cycle, and chromatin remodeling across
      multiple cancers. 

PMID- 25374458
TI  - The axis of progression of disease.
AB  - Starting with genetic or environmental perturbations, disease progression can
      involve a linear sequence of changes within individual cells. More often,
      however, a labyrinth of branching consequences emanates from the initial events.
      How can one repair an entity so fine and so complex that its organization and
      functions are only partially known? How, given the many redundancies of metabolic
      pathways, can interventions be effective before the last redundant element has
      been irreversibly damaged? Since progression ultimately proceeds beyond a point
      of no return, therapeutic goals must target earlier events. A key goal is
      therefore to identify early changes of functional importance. Moreover, when
      several distinct genetic or environmental causes converge on a terminal
      phenotype, therapeutic strategies that focus on the shared features seem unlikely
      to be useful - precisely because the shared events lie relatively downstream
      along the axis of progression. We therefore describe experimental strategies that
      could lead to identification of early events, both for cancer and for other
      diseases. 

PMID- 25374460
TI  - Predictors of willingness to participate in health insurance services among the
      community of jimma town, southwest ethiopia.
AB  - Health insurance schemes are increasingly recognized as tools to finance health
      care provision in low-income countries. The main objective of this study was to
      find out the awareness of and demand for health insurance and to identify those
      reasons that influence the demand in Jimma town, southwest Ethiopia. We conducted
      a community-based cross-sectional quantitative study on 741 households from
      December 1 to December 31, 2012. Data were analyzed using Statistical Package for
      Social Sciences (SPSS) version 16. Presence of chronic illness in the family was
      the predictor of the willingness to take part in health insurance. Most of the
      participants have awareness about insurance, but they did little and/or gave
      unrelated explanation about health insurance. Only half of the participants
      (51.5%) wanted to have health insurance. Major reasons for not being willing to
      participate in health insurance were religious values and beliefs, ability to pay
      for their health-care cost, and feeling of being unable to pay the premium
      because of low income. 

PMID- 25374459
TI  - Antimicrobial peptides and their analogs: searching for new potential
      therapeutics.
AB  - Antimicrobial peptides (AMPs) are an essential part of innate immunity. These
      compounds have been considered as potential therapeutics because of their broad
      spectrum activities and proven ability to avoid antimicrobial resistance, but
      their clinical and commercial developments have some limitations, such as
      susceptibility to proteases and a high cost of peptide production. To overcome
      these problems, many researchers have tried to develop short active peptides,
      their modifications and mimics with better properties while retaining their basic
      features of natural AMPs such as cationic charge and the amphipathic structure. 

PMID- 25374461
TI  - Optogenetic Control of Apoptosis in Targeted Tissues of Xenopus laevis Embryos.
AB  - KillerRed (KR) is a recently discovered fluorescent protein that, when activated
      with green light, releases reactive oxygen species (ROS) into the cytoplasm,
      triggering apoptosis in a KR-expressing cell. This property allows for the use of
      KR as a means of killing cells in an organism with great temporal and spatial
      specificity, while minimizing the nonspecific effects that can result from
      mechanical or chemical exposure damage techniques. Such optogenetic control of
      cell death, and the resulting ability to induce the targeted death of specific
      tissues, is invaluable for regeneration/repair studies-particularly in Xenopus
      laevis, where apoptosis plays a key role in regeneration and repair. We here
      describe a method by which membrane-bound KR, introduced to Xenopus embryos by
      mRNA microinjection, can be activated with green light to induce apoptosis in
      specific organs and tissues, with a focus on the developing eye and pronephric
      kidney. 

PMID- 25374462
TI  - Perceptions of received information, social support, and coping in patients with
      pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.
AB  - Patients with a life-limiting diagnosis of pulmonary arterial hypertension (PAH)
      or chronic thromboembolic pulmonary hypertension (CTEPH) need disease-specific
      information, ability to cope, and functioning social networks. This cohort study
      investigated the experiences of PAH and CTEPH patients who received information
      about their diagnosis, treatment, and management, in addition to coping and
      social support. Sixty-eight adult patients (mean +/- SD, age 67 +/- 14; 66%
      women) were included. A total of 54% of the patients wanted more information.
      Patients received information mostly in areas concerning medical test procedures,
      the diagnosis, disease severity, possible disease causes, and how to manage their
      disease. Coping ability was significantly better in patients who were satisfied
      with the received information (P = 0.0045). The information given to PAH or CTEPH
      patients and their communication with healthcare professionals can be greatly
      improved. Gaps in information and misunderstandings can be avoided by working in
      cooperation with the patients, their relatives, and within the PAH team. 

PMID- 25374463
TI  - Bupivacaine Lozenge Compared with Lidocaine Spray as Topical Pharyngeal
      Anesthetic before Unsedated Upper Gastrointestinal Endoscopy: A Randomized,
      Controlled Trial.
AB  - Unsedated upper gastrointestinal endoscopy (UGE) can induce patient discomfort,
      mainly due to a strong gag reflex. The aim was to assess the effect of a
      bupivacaine lozenge as topical pharyngeal anesthetic compared with standard
      treatment with a lidocaine spray before UGE. Ninety-nine adult outpatients
      undergoing unsedated diagnostic UGE were randomized to receive either a
      bupivacaine lozenge (L-group, n = 51) or lidocaine spray (S-group, n = 42).
      Primary objective was assessment of patient discomfort including acceptance of
      the gag reflex during UGE. The L-group assessed the discomfort significantly
      lower on a visual analog scale compared with the S-group (P = 0.02). There was
      also a significant difference in the four-point scale assessment of the gag
      reflex (P = 0.03). It was evaluated as acceptable by 49% in the L-group compared
      with 31% in the S-group. A bupivacaine lozenge compared with a lidocaine spray
      proved to be a superior option as topical pharyngeal anesthetic before an UGE. 

PMID- 25374464
TI  - The prevalence of smoking and its associated factors among military personnel in
      Kingdom of Saudi Arabia: A national study.
AB  - AIM: The aim was to measure the prevalence of smoking and identify its potential
      predictors among military personnel in Kingdom of Saudi Arabia (KSA). MATERIALS
      AND METHODS: This cross-sectional study was carried out among military personnel
      in the five military regions of KSA between January 2009 and January 2011. The
      sample of 10,500 military personnel in the Saudi Armed Forces was equally divided
      among the five regions with a ratio 3:7 for officers and soldiers. A multistage
      stratified random sampling was used to recruit participants in the four services
      of the armed forces in the five regions. Information on sociodemographic
      characteristics with a detailed history of smoking was collected by means of a
      self-administered questionnaire. Bivariate analysis was used to identify the
      factors associated with smoking, and multiple logistic regression analysis to
      discover its potential predictors. RESULTS: About 35% of the sample was current
      smokers, with higher rates among soldiers. The eastern region had the highest
      rate (43.0%), and the southern region the lowest (27.5%). Navy personnel had a
      higher risk of being current smokers (40.6%), and the air defense the lowest risk
      (31.0%). Multivariate analysis identified working in the navy, and low income as
      positive predictors of current smoking, while residing in the southern region,
      older age, years of education, being married, and having an officer rank were
      negative (protective) factors. CONCLUSION: Smoking is prevalent among military
      personnel in KSA, with higher rates in the Navy and Air Force, among privates,
      younger age group, lower education and income, and divorced/widowed status.
      Measures should be taken to initiate programs on smoking cessation that involve
      changes in the environment that is likely to promote this habit.

PMID- 25374465
TI  - The impact of Vitamin D deficiency on asthma, allergic rhinitis and wheezing in
      children: An emerging public health problem.
AB  - BACKGROUND: Vitamin D deficiency has been declared a public health problem for
      both adults and children worldwide. Asthma and related allergic diseases are the
      leading causes of morbidity in children. The objective of this study was to
      investigate the potential role of Vitamin D deficiency in childhood asthma and
      other allergic diseases such as allergic rhinitis and wheezing. MATERIALS AND
      METHODS: This cross-sectional study was conducted in Primary Health Care Centers
      (PHCs), from March 2012 to October 2013. A total of 2350 Qatari children below
      the age of 16 were selected from PHCs, and 1833 agreed to participate in this
      study giving a response rate of (78%). Face-to-face interviews with parents of
      all the children were based on a questionnaire that included variables such as
      socio-demographic information, assessment of nondietary covariates, Vitamin D
      intake, type of feeding, and laboratory investigations. Their health status was
      assessed by serum Vitamin D (25-hydoxyvitamin D), family history and body mass
      index. RESULTS: Most of the children who had asthma (38.5%), allergic rhinitis
      (34.8%) and wheezing (35.7%) were below 5 years. Consanguinity was significantly
      higher in parents of children with allergic rhinitis (48.6%), followed by those
      with asthma (46.4%) and wheezing (40.8%) than in healthy children (35.9%) (P <
      0.001). The proportion of severe Vitamin D deficiency was significantly higher in
      children with wheezing (23.4%), allergic rhinitis (18.5%), and asthma (17%) than
      in healthy children (10.5%). Exposure to the sun was significantly less in
      Vitamin D deficient children with asthma (60.3%), allergic rhinitis (62.5%) and
      wheezing (64.4%) than in controls (47.1%) (P = 0.008). It was found that Vitamin
      D deficiency was a significant correlate for asthma (odds ratio [OR] =2.31; P <
      0.001), allergic rhinitis (OR = 1.59; P < 0.001) and wheezing (relative risk =
      1.29; P = 0.05). CONCLUSION: The study findings revealed a high prevalence of
      Vitamin D deficiency in children with asthma and allergic diseases. Vitamin D
      deficiency was a strong correlate for asthma, allergic rhinitis and wheezing.

PMID- 25374466
TI  - Respiratory health of a population of welders.
AB  - OBJECTIVE: The aim was to identify respiratory symptoms and respiratory function
      of welders in comparison to a "nonexposed group." MATERIALS AND METHODS:
      Information was collected by means of a questionnaire completed during an
      interview, and spirometry of all subjects. RESULTS: This study involved 41
      welders and 41 comparable nonexposed group. Sixteen (39%) welders reported
      bringing up phlegm from the chest first thing in the morning, compared with seven
      individuals (17.1%) in the nonexposed group. The difference is significant (Chi
      square = 3.87 odds ratio (OR) 3.11 [1.0-9.9], P = 0.0182). Eleven welders had
      chronic bronchitis, which they had experienced most days for as long as 3 months,
      compared with one person in the nonexposed group. The difference was
      statistically significant, and OR was 1.7 (95% confidence interval 1.19-2.53). On
      the other hand, the difference in cough, shortness of breath and lung function
      was statistically insignificant when the welders were compared with the
      nonexposed group. CONCLUSION: This study showed more respiratory complaints,
      particularly chronic bronchitis, among welders compared with the nonexposed
      group, which is believed to be the result of welding emissions. Spirometry showed
      no impairment in lung function in both the welders and the nonexposed group.

PMID- 25374467
TI  - Prevalence and pattern of lipid disorders in Saudi patients with angiographically
      documented coronary artery disease.
AB  - OBJECTIVE: The aim of the study was to assess the prevalence and patterns of
      dyslipidemia in Saudi patients with angiographically documented coronary artery
      disease (CAD). MATERIALS AND METHODS: This is a cross-sectional, hospital-based
      study, which was conducted on all Saudi patients who underwent coronary
      angiography under the author's personal care and were found to have > 50%
      coronary stenosis. Fasting lipid profile was measured in all patients during the
      admission for the coronary angiography. RESULTS: Two hundred and ninety-five
      patients were included in the study. The mean age (+/-Standard deviation) was
      55.1 +/- 11, ranging from 17 to 86 years. The majority of patients were males:
      229 (77.6%). Mean total cholesterol was 175.6 +/- 47.6 mg/dl, mean low-density
      lipoprotein cholesterol (LDL-C) was 111.3 +/- 40.3 mg/dl, mean high density
      lipoprotein cholesterol (HDL-C) was 38.27 +/- 9.5 mg/dl and mean triglyceride
      level was 141.8 +/- 74.8 mg/dl. 21 (7.1%) patients had normal coronary arteries,
      107 (36.3%) had one vessel disease, 78 (26.4%) had two vessel disease and 89
      (30.2%) had three vessel disease. There was a significant correlation between the
      extent of CAD and age (P = 0.003), sex (P = 0.0002), total cholesterol (P = 0.02)
      and low HDL-C (P < 0.001. 21 (7.1%) patients were asymptomatic, 110 (37.3%) had
      stable angina, 127 (43.1%) had none ST elevation acute coronary syndrome, 20
      (6.8%) had ST elevation myocardial infarction and 17 (5.7%) had heart failure.
      There was also a significant correlation between age (P = 0.03), sex (P < 0.001),
      LDL-C (P = 0.005) and low HDL-C (P < 0.001) and the severity of CAD. CONCLUSION:
      Dyslipidemia is a very prevalent risk factor in Saudi patients with CAD. Low HDL
      C was the most frequent lipid abnormality, which significantly impacts on the
      extent of the CAD.

PMID- 25374468
TI  - Metabolic syndrome: Risk factors among adults in Kingdom of Saudi Arabia.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a cluster of established cardiovascular
      risk factors that collectively increase predisposition to major chronic diseases,
      including heart diseases and diabetes mellitus. Citizens of developing countries
      such as Saudi Arabia are at risk for MetS as a result of industrialization and
      accessibility to fast foods. In this epidemiologic study, the kingdom-wide
      prevalence of MetS is determined. MATERIALS AND METHODS: A total of 4578 Saudis
      aged 15-64 was randomly selected from 20 regions in Saudi Arabia. Anthropometrics
      were collected, and fasting blood samples collected to ascertain fasting blood
      glucose and lipid profile. Components of full MetS as defined by the
      International Diabetes Federation were used for screening. RESULTS: The overall
      prevalence of MetS is 28.3%. Prevalence was significantly higher in males than in
      females (31.4 vs. 25.2%; P = 0.001). Prevalence of MetS was the highest in the
      northern and central region, and showed a parallel increase with age, and
      inversely with educational status. Region was also a significant contributor to
      MetS. CONCLUSION: Despite accumulating evidence of an epidemic, MetS remains
      largely unresolved in the kingdom. Aggressive public campaign should be launched,
      and policies implemented to control any future damage of MetS in the kingdom.

PMID- 25374469
TI  - The impact of adding weight-bearing exercise versus nonweight bearing programs to
      the medical treatment of elderly patients with osteoporosis.
AB  - BACKGROUND: Osteoporosis is a major public health problem affecting the elderly
      population, particularly women. The objective of the study was to evaluate the
      effects of adding weight-bearing exercise as opposed to nonweight-bearing
      programs to the medical treatment of bone mineral density (BMD) and health
      related quality of life (HRQoL) of elderly patients with osteoporosis. MATERIALS
      AND METHODS: Participating in the study were 40 elderly osteoporotic patients (27
      females and 13 males), with ages ranging from 60 to 67 years, who were receiving
      medical treatment for osteoporosis. They were assigned randomly into two groups:
      Group-I: Twenty patients practiced weight-bearing exercises. Group-II: Twenty
      patients did nonweight-bearing exercises. All patients trained for 45-60
      min/session, two sessions/week for 6 months. BMD of the lumbar spine, right neck
      of femur, and right distal radial head of all patients were measured by dual
      energy X-ray absorptiometry before and after both treatment programs. In
      addition, the QoL was measured by means of the HRQoL "ECOS-16" questionnaire.
      RESULTS: T-tests proved that mean values of BMD of the lumbar spine, right neck
      of femur and right distal radial head were significantly increased in both groups
      with greater improvement in the weight-bearing group. The QoL was significantly
      improved in both groups, but the difference between them was not significant.
      CONCLUSION: Addition of weight-bearing exercise program to medical treatment
      increases BMD more than nonweight-bearing exercise in elderly subjects with
      osteoporosis. Furthermore, both weight-bearing and nonweight-bearing exercise
      programs significantly improved the QoL of patients with osteoporosis.

PMID- 25374470
TI  - Prevalence of suspected tuberculosis in the Kingdom of Saudi Arabia according to
      conventional and molecular methods.
AB  - BACKGROUND: Although the prevalence of suspected tuberculosis (TB) in the Kingdom
      of Saudi Arabia remains high, there has been a modest decrease in recent years.
      In this multi-center cross-sectional study, the prevalence of TB was determined
      by various techniques with the aim of identifying differences and indicating
      where there is uniformity in findings. MATERIALS AND METHODS: A total of 3404
      samples were collected from Saudi TB patients from different regions in Saudi
      Arabia: Riyadh, Dammam, Jeddah, Madinah, Hail, Qassim, Jazan, and Taif. Different
      techniques including Ziehl-Neelsen (ZN), Mycobacteria growth indicator tube
      (MGiT), Lowenstein-Jensen (LJ), and polymerase chain reaction (PCR) were used to
      screen for the presence of Mycobacterium tuberculosis (MTB). RESULTS: ZN stain
      showed that Riyadh and Dammam had the highest prevalence of MTB with 22% and 21%,
      respectively, while prevalence was lowest in Jazan and Hail with an incidence of
      2% and 3%, respectively. MGiT culture showed that Riyadh, Dammam, and Jeddah had
      the highest prevalence with a rate of 26%, 22%, and 22%, respectively. LJ culture
      showed the highest prevalence in Riyadh and Dammam with 22% and 21%,
      respectively. Of all the techniques, the highest detection rate was by PCR which
      was 10.46% while ZN stain technique was 6.64%, for MGiT culture it was 8.34%, and
      for LJ culture it was 7.7%. CONCLUSION: This study is the first in which
      different methods have been used for detection in the various regions of Saudi
      Arabia. Collected data are important not only for patients and physicians but for
      future epidemiological studies to monitor the spread of MTB infection in Saudi
      Arabia.

PMID- 25374471
TI  - Suitability assessment of health education brochures in Qassim province, Kingdom
      of Saudi Arabia.
AB  - BACKGROUND: Health education is the cornerstone of primary health care. Health
      education materials distributed to the community should, therefore, be suitable
      and effective. The purpose of this study was to evaluate the health education
      brochures, designed and disseminated by Ministry of Health institutions in the
      Qassim province. MATERIALS AND METHODS: The study was a cross-sectional review of
      health education brochures. We used a structured evaluation form, comprising
      general information on the brochures and a modified Suitability Assessment of
      Materials (SAM) score sheet. The SAM consisting of 22 criteria in six groups,
      includes content, literacy demands, graphics, layout/typography, learning
      stimulation/motivation, and cultural appropriateness. SAM criteria categorize
      written material into "superior," "adequate" and "not suitable." Two qualified
      consultant family physicians evaluated the brochures. Data were analyzed using
      Epi Info version 3.4 statistical package. RESULTS: We evaluated 110 brochures,
      the majority of which addressed chronic health conditions such as mental health,
      diabetes mellitus and hypertension. Seventy-four (67.3%) brochures were evaluated
      as "adequate," 34 (30.9%) as "not suitable" and 2 (1.8%) as "superior." "Cultural
      appropriateness" was the highest scoring factor, with 92 (83.6%) brochures
      falling into either the "superior" or "adequate" category. With regard to
      "content," 88 (80.0%) brochures fell into either the "superior" or "adequate"
      category. This was the second highest scoring factor. Graphics was the factor
      that scored the least. Seventy-five (68.2%) brochures were rated in this factor
      as "not suitable." CONCLUSIONS: Although two-thirds of our brochures were
      considered "adequate," the majority needed improvement to their graphics and
      learning stimulation factors. We recommend that guidelines for designing health
      education brochures should be formulated to improve the quality of health
      education brochures.

PMID- 25374472
TI  - An unusual case of chronic prostatitis caused by Haemophilus influenzae in an
      elderly Saudi patient: A case report and literature review.
AB  - Haemophilus influenzae has been reported on rare occasions as the cause of
      prostatitis and urinary tract infections. Here, we report a rare case of chronic
      prostatitis in a 52-year-old male with benign prostatic hypertrophy and discuss
      the possible underestimation of the true incidence of H. influenzae in
      genitourinary infections. This organism was identified only by its growth on
      chocolate agar, a medium that is not commonly used for urine cultures. 

PMID- 25374473
TI  - Obesity and gastric balloon.
AB  - BACKGROUND: The obesity epidemic, which is among the most common nutritional
      disorders, is rising rapidly worldwide. It leads to several health problems such
      as metabolic disorders, stroke, and even cancer. Efforts to control obesity with
      exercise and diet have a limited value in obese patients and different approaches
      to do this have been tried. In this paper, we share our experience with
      bioenteric intragastric balloon (BIB) in treating obesity: Its safety,
      tolerability, and its efficacy in weight reduction. MATERIALS AND METHODS: From
      January 2009 to September 2012, a total of 190 gastric balloons was inserted on
      patients at the endoscopy unit in King Fahd Hospital of the University, Al
      Khobar. This is an evaluation of the first 100 patients. All the patients had a
      body mass index of over 30 kg/m(2) and were within the age range of 17-55 with a
      mean age of 32 years. After consent, preballoon investigation tests and
      anesthesia evaluation, BIB was inserted under monitored anesthesia care sedation
      in the endoscopy suite. The balloon was filled with 500-700 mls of stained
      saline. All patients' were given an analgesic and antiemetic for a week and
      antisecretory proton pump inhibitor's for 6 months. Diet and the importance of
      the exercise were part of the preballoon insertion phase and protocol. The
      balloon was removed after 6-12 months. RESULTS: The weight loss response to BIB
      in the 100 patients are classified into four groups: In the uncooperative,
      noncompliant patients - the maximum weight loss was 7 kg, while in the most
      compliant patients the weight loss reached up to 39 kg. In addition, there was
      significant improvement into diabetes mellitus, hypertension, dyslipidemia, and
      fatty liveras. Its safety and tolerability were extremely acceptable. CONCLUSION:
      Our data indicates that in well-selected patients, BIB is an effective device,
      which with minimum complications helps to achieve body weight loss and resolve
      many obesity related morbidities in cooperative and dedicated obese patients.

PMID- 25374474
TI  - Cleanness of the public restroom in a rural municipality, Thailand.

PMID- 25374475
TI  - Association of morning illumination and window covering with mood and sleep among
      post-menopausal women.
AB  - The antidepressant and sleep-promoting effects of light exposure might be useful
      for treating age-related mood and sleep disorders. In view of recent evidence
      suggesting beneficial effects of morning light, this study examined the
      associations of mood and sleep with morning light exposure, 24 h environmental
      illumination, and the degree to which the volunteers' bedroom windows were
      covered in the morning. We examined 459 postmenopausal women participating an
      ancillary study of the Women's Health Initiative conducted at the University of
      California, San Diego Clinical Center, San Diego, CA, USA. At baseline,
      volunteers completed a 4-week sleep-recall questionnaire. Volunteers were then
      assessed for 5-7 days in their home environments with actigraphic wrist monitors.
      During home recording, self-reported mood was assessed. Morning illumination
      during the first 4 h after arising, 24-h illumination mesor (cosine-fitted mean),
      and illumination acrophase (cosine-fitted peak time) were calculated. Sleep was
      scored each night using validated wrist actigraphic methods. A sleep diary was
      completed each morning. During two 24-h periods, urine was collected
      approximately every 2 h during wakefulness and following any voidings during the
      sleep period. Cosine-fitting established the acrophase of urinary 6
      sulfatoxymelatonin (aMT6s) excretion. Morning illumination and 24-h illumination
      were modestly associated with better mood and sleep. Associations of light with
      mood and sleep were consistently greater for subjects whose body clocks were
      delayed relative to the group median. Less morning window covering in the
      subjects' bedrooms was associated with more morning light and less depressed
      mood. The results suggest that both morning and 24-h light exposure may be
      beneficial for older adults.

PMID- 25374476
TI  - Epidemiology of exercise and sleep.
AB  - Although exercise is widely believed to improve sleep, experimental evidence has
      found acute and chronic exercise to exert only modest effects on subsequent
      sleep. However, these studies are limited in that they have primarily used good
      sleepers (floor/ceiling effects). In contrast to experimental studies,
      epidemiologic studies have consistently reported significant positive
      associations between self-reported exercise habits and better self-reported
      sleep. This association has been confirmed across a wide range of demographics.
      Nonetheless, epidemiologic studies on this topic have also had limitations. They
      have often assessed exercise and sleep using instruments of dubious validity.
      Moreover, the studies have generally not included clinical diagnoses of sleep
      disorders. Thus, the clinical relevance of these findings is unclear. In
      addition, possible alternative explanations for the association of exercise and
      improved sleep have often not been controlled (e.g. bright light, other healthy
      behaviors). This review will focus on these epidemiologic studies. We will review
      and critique representative survey and epidemiologic studies of exercise and
      sleep and discuss directions for future research in this area.

PMID- 25374477
TI  - Children living near a sanitary landfill have increased breath methane and
      Methanobrevibacter smithii in their intestinal microbiota.
AB  - This study evaluated the breath CH4 excretion and concentration of M. smithii in
      intestinal microbiota of schoolchildren from 2 slums. One hundred and eleven
      children from a slum near a sanitary landfill, 35 children of a slum located away
      from the sanitary landfill, and 32 children from a high socioeconomic level
      school were included in the study. Real-time PCR was performed to quantify the M.
      smithii nifH gene and it was present in the microbiota of all the participating
      children, with higher (P < 0.05) concentrations in those who lived in the slum
      near the landfill (3.16 * 10(7) CFU/g of feces), comparing with the children from
      the slum away from the landfill (2.05 * 10(6) CFU/g of feces) and those from the
      high socioeconomic level group (3.93 * 10(5) CFU/g of feces). The prevalence of
      children who present breath methane was 53% in the slum near the landfill, 31% in
      the slum further away from the landfill and, 22% in the high socioeconomic level
      group. To live near a landfill is associated with higher concentrations of M.
      smithii in intestinal microbiota, comparing with those who live away from the
      landfill, regardless of their socioeconomics conditions. 

PMID- 25374478
TI  - A Two-Pass Exact Algorithm for Selection on Parallel Disk Systems.
AB  - Numerous OLAP queries process selection operations of "top N", median, "top 5%",
      in data warehousing applications. Selection is a well-studied problem that has
      numerous applications in the management of data and databases since, typically,
      any complex data query can be reduced to a series of basic operations such as
      sorting and selection. The parallel selection has also become an important
      fundamental operation, especially after parallel databases were introduced. In
      this paper, we present a deterministic algorithm Recursive Sampling Selection
      (RSS) to solve the exact out-of-core selection problem, which we show needs no
      more than (2 + epsilon) passes (epsilon being a very small fraction). We have
      compared our RSS algorithm with two other algorithms in the literature, namely,
      the Deterministic Sampling Selection and QuickSelect on the Parallel Disks
      Systems. Our analysis shows that DSS is a (2 + epsilon)-pass algorithm when the
      total number of input elements N is a polynomial in the memory size M (i.e., N =
      Mc for some constant c). While, our proposed algorithm RSS runs in (2 + epsilon)
      passes without any assumptions. Experimental results indicate that both RSS and
      DSS outperform QuickSelect on the Parallel Disks Systems. Especially, the
      proposed algorithm RSS is more scalable and robust to handle big data when the
      input size is far greater than the core memory size, including the case of N ? Mc
      .

PMID- 25374479
TI  - Jails as Public Health Partners: Incarceration and Disparities Among Medically
      Underserved Men.
AB  - There were nearly 12 million admissions to U.S. jails in 2011, the majority of
      them Black or Hispanic. We analyzed data on men's health screenings from the last
      Bureau of Justice Statistics Survey of Inmates in Local Jails. Black and Hispanic
      men had the same or higher odds of reporting nearly all types of screenings
      compared to White male inmates. Because many prisoners are medically underserved,
      jails can be crucial public health partners in reducing disparities by
      identifying men in need of health care. The anticipated expansion of Medicaid
      eligibility in 2014 constitutes an important opportunity for correctional and
      public health authorities to work together to ensure linkage to care following
      release from incarceration.

PMID- 25374480
TI  - Prevalence of Mental Health Issues in the Borderlands: A Comparative Perspective.
AB  - The purpose of this paper is to (a) examine the results of a binational study of
      two colonias near El Paso, Texas, and Ciudad Juarez, Mexico, focusing on mental
      health and (b) analyze those results in relation to the existing literature on
      Hispanic mental health to determine how border regions compare with Hispanic
      enclaves in nonborder regions. We focus on gender, birthplace, length of
      residency, and level of acculturation correlated with self-reported diagnoses of
      depression in our analysis. Our survey instrument incorporates portions of the
      Behavioral Risk Factor and Surveillance Survey; the SF36, version 2; and the CAGE
      scale for alcohol use and abuse. We found that birthplace, acculturation, and
      length of residency at the border did not correlate in the same ways to mental
      health issues as in nonborder regions.

PMID- 25374481
TI  - Corner Store Inventories, Purchases, and Strategies for Intervention: A Review of
      the Literature.
AB  - INTRODUCTION: An increasingly popular strategy to improving the food retail
      environment and promoting healthy eating in low-income and minority communities
      is the corner store conversion. This approach involves partnering with small
      'corner' food stores to expand access to high-quality fruits, vegetables, and
      other healthy foods. METHODS: We conducted a structured review of the literature
      to assess inventories and sales in corner stores, as well as to identify
      intervention strategies employed by corner store conversions. RESULTS: Our review
      returned eight descriptive studies that discussed corner store inventories and
      sales, as well as ten intervention studies discussing six unique corner store
      conversion interventions in the United States, the Marshall Islands, and Canada.
      Common intervention strategies included: 1) partnering with an existing store, 2)
      stocking healthy foods, and 3) social marketing and nutrition education. We
      summarize each strategy and review the effectiveness of overall corner store
      conversions at changing peoples' food purchasing, preparation, and consumption
      behaviors. CONCLUSIONS: Consumption of fresh, healthy, affordable foods could be
      improved by supporting existing retailers to expand their selection of healthy
      foods and promoting healthy eating at the neighborhood level. Additional corner
      store conversions should be conducted to determine the effectiveness and
      importance of specific intervention strategies.

PMID- 25374482
TI  - Lactose-free milk prolonged endurance capacity in lactose intolerant Asian males.
AB  - BACKGROUND: Several studies on Caucasian volunteers have proven that milk is an
      effective recovery drink for athletes. Such benefit, however, cannot be directly
      applied to the lactose-intolerant Asian population. This study investigated the
      effects of ingesting water (WT), sports drink (SPD) and lactose-free milk (LFM)
      on cycling capacity. METHODS: Ten healthy young men completed 3 randomized
      experimental trials. Each trial consisted of an intermittent glycogen depleting
      session, a 2 h recovery period during which they ingested the test drink,
      followed by cycling at 70% of their maximum oxygen consumption (VO2max) to
      volitional exhaustion. Each trial was separated by at least one week. RESULTS:
      There were no complaints or symptoms of lactose intolerance during any of the
      trials. The cycling periods were different (p < 0.05) amongst the 3 trials,
      namely, lactose-free milk (LFM; 69.6 +/- 14.0 min), sports drink (SPD; 52.1 +/-
      11.6 min), and water (WT; 36.0 +/- 11.1 min), respectively. The VO2 and VCO2 of
      LFM (30 +/- 4 and 29 +/- 4 ml/kg/min) were lower (p < 0.05) than that of SPD (34
      +/- 4 and 34 +/- 4 ml/kg/min) and WT (35 +/- 4 and 33 +/- 5 ml/kg/min). There
      were no differences (p = 0.45) in VO2 and VCO2 between SPD and WT. Mean rating of
      perceived exertion was lowest in LFM (14 +/- 5; p < 0.05), while no difference
      was found between the other two trials (SPD: 16 +/- 4 and WT: 16 +/- 4; p =
      0.18). CONCLUSION: Lactose-free milk is likely to be an effective recovery drink
      for enhancing subsequent cycling capacity in lactose intolerant Asian males.

PMID- 25374483
TI  - Sense of Community Among Individuals in Substance Abuse Recovery.
AB  - This study assessed the psychometric properties of the Psychological Sense of
      Community Scale (PSCS). Psychological sense of community is a construct that has
      been developed primarily in the field of community psychology and deals with the
      feelings of connectedness, group membership, and need fulfillment that members of
      small groups or larger communities may have toward other members. The current
      research explores this concept in the evaluation of Oxford Houses, residential
      homes designed to provide mutual support to individuals recovering from substance
      abuse dependence, through the use of the PSCS. Overall, the PSCS was a
      multidimensional scale exhibiting a cluster of negatively phrased items with a
      large number of highly loading items. With a three factor structure, two factors
      were nearly perfectly correlated and neither sex nor race bias affected the
      initial formulation. However, sex and race were significant (but of small
      magnitude) covariates in a later sample, and highly reliable subscales were
      formulated with five items. Taken together, the PSCS was capable of performing as
      an acceptable measurement model in latent analysis.

PMID- 25374484
TI  - Green approach for fabrication and applications of zinc oxide nanoparticles.
AB  - Zinc oxide nanoparticles (ZnO-NPs) are known to be one of the multifunctional
      inorganic compounds which are widely used in everyday applications. This study
      aims to fabricate ZnO-NPs using grapefruit (Citrus paradisi) peel extract with
      particle size ranging from 12 to 72 nm. Structural, morphological, and optical
      properties of the synthesized nanoparticles have been characterized by using UV
      Vis spectrophotometer, TEM, DLS, and FTIR analysis. They show the significant
      photocatalytic degradation efficiency (>56%, 10 mg/L, 6 h) against methylene blue
      and antioxidant efficacy (>=80% for 1.2 mM) against 1,1-diphenyl-2
      picrylhydrazyl. From the results obtained it is suggested that green ZnO-NPs
      could be used effectively in environmental safety applications and also can
      address future medical concerns. 

PMID- 25374485
TI  - Distinguishing between the metabolome and xenobiotic exposome in environmental
      field samples analysed by direct-infusion mass spectrometry based metabolomics
      and lipidomics.
AB  - Environmental metabolomics is increasingly used to investigate organismal
      responses to complex chemical mixtures, including waste water effluent (WWE). In
      parallel, increasingly sensitive analytical methods are being used in
      metabolomics studies, particularly mass spectrometry. This introduces a
      considerable, yet overlooked, challenge that high analytical sensitivity will not
      only improve the detection of endogenous metabolites in biological specimens but
      also exogenous chemicals. If these often unknown xenobiotic features are not
      removed from the "biological" dataset, they will bias the interpretation and
      could lead to incorrect conclusions about the biotic response. Here we illustrate
      and validate a novel workflow classifying the origin of peaks detected in
      biological samples as: endogenous, xenobiotics, or metabolised xenobiotics. The
      workflow is demonstrated using direct infusion mass spectrometry-based
      metabolomic analysis of testes from roach exposed to different concentrations of
      a complex WWE. We show that xenobiotics and their metabolic products can be
      detected in roach testes (including triclosan, chloroxylenol and chlorophene),
      and that these compounds have a disproportionately high level of statistical
      significance within the total (bio)chemical changes induced by the WWE. Overall
      we have demonstrated that this workflow extracts more information from an
      environmental metabolomics study of complex mixture exposures than was possible
      previously.

PMID- 25374486
TI  - Metabolomic profiling of the purple sulfur bacterium Allochromatium vinosum
      during growth on different reduced sulfur compounds and malate.
AB  - Environmental fluctuations require rapid adjustment of the physiology of
      bacteria. Anoxygenic phototrophic purple sulfur bacteria, like Allochromatium
      vinosum, thrive in environments that are characterized by steep gradients of
      important nutrients for these organisms, i.e., reduced sulfur compounds, light,
      oxygen and carbon sources. Changing conditions necessitate changes on every level
      of the underlying cellular and molecular network. Thus far, two global analyses
      of A. vinosum responses to changes of nutritional conditions have been performed
      and these focused on gene expression and protein levels. Here, we provide a study
      on metabolite composition and relate it with transcriptional and proteomic
      profiling data to provide a more comprehensive insight on the systems level
      adjustment to available nutrients. We identified 131 individual metabolites and
      compared availability and concentration under four different growth conditions
      (sulfide, thiosulfate, elemental sulfur, and malate) and on sulfide for a
      DeltadsrJ mutant strain. During growth on malate, cysteine was identified to be
      the least abundant amino acid. Concentrations of the metabolite classes "amino
      acids" and "organic acids" (i.e., pyruvate and its derivatives) were higher on
      malate than on reduced sulfur compounds by at least 20 and 50 %, respectively.
      Similar observations were made for metabolites assigned to anabolism of glucose.
      Growth on sulfur compounds led to enhanced concentrations of sulfur containing
      metabolites, while other cell constituents remained unaffected or decreased.
      Incapability of sulfur globule oxidation of the mutant strain was reflected by a
      low energy level of the cell and consequently reduced levels of amino acids (40
      %) and sugars (65 %).

PMID- 25374487
TI  - De novo synthesize of bile acids in pulmonary arterial hypertension lung.
AB  - Although multiple, complex molecular studies have been done for understanding the
      development and progression of pulmonary hypertension (PAH), little is known
      about the metabolic heterogeneity of PAH. Using a combination of high-throughput
      liquid-and-gas-chromatography-based mass spectrometry, we found bile acid
      metabolites, which are normally product derivatives of the liver and gallbladder,
      were highly increased in the PAH lung. Microarray showed that the gene encoding
      cytochrome P450 7B1 (CYP7B1), an isozyme for bile acid synthesis, was highly
      expressed in the PAH lung compared with the control. CYP7B1 protein was found to
      be primarily localized on pulmonary vascular endothelial cells suggesting de novo
      bile acid synthesis may be involved in the development of PAH. Here, by profiling
      the metabolomic heterogeneity of the PAH lung, we reveal a newly discovered
      pathogenesis mechanism of PAH.

PMID- 25374489
TI  - Could early anti-tumor necrosis factor therapy change the prognosis of Crohn's
      disease?

PMID- 25374488
TI  - Novel metabolic features in Acinetobacter baylyi ADP1 revealed by a multiomics
      approach.
AB  - Expansive knowledge of bacterial metabolism has been gained from genome
      sequencing output, but the high proportion of genes lacking a proper functional
      annotation in a given genome still impedes the accurate prediction of the
      metabolism of a cell. To access to a more global view of the functioning of the
      soil bacterium Acinetobacter baylyi ADP1, we adopted a multi 'omics' approach.
      Application of RNA-seq transcriptomics and LC/MS-based metabolomics, along with
      the systematic phenotyping of the complete collection of single-gene deletion
      mutants of A. baylyi ADP1 made possible to interrogate on the metabolic
      perturbations encountered by the bacterium upon a biotic change. Shifting the
      sole carbon source from succinate to quinate elicited in the cell not only a
      specific transcriptional response, necessary to catabolize the new carbon source,
      but also a major reorganization of the transcription pattern. Here, the
      expression of more than 12 % of the total number of genes was affected, most of
      them being of unknown function. These perturbations were ultimately reflected in
      the metabolome, in which the concentration of about 50 % of the LC/MS-detected
      metabolites was impacted. And the differential regulation of many genes of
      unknown function is probably related to the synthesis of the numerous
      unidentified compounds that were present exclusively in quinate-grown cells.
      Together, these data suggest that A. baylyi ADP1 metabolism involves unsuspected
      enzymatic reactions that await discovery.

PMID- 25374490
TI  - Risk Factors for Delayed Recurrence of Clostridium difficile Infection.

PMID- 25374491
TI  - Impact of sigmoidoscopy and colonoscopy on colorectal cancer incidence and
      mortality: an evidence-based review of published prospective and retrospective
      studies.
AB  - Screening for colorectal cancer (CRC) using sigmoidoscopy or colonoscopy is now
      common in many developed countries. This concise, evidence-based review looks at
      the impact of sigmoidoscopy or colonoscopy screening on CRC incidence, CRC
      mortality and overall mortality. Data from controlled retrospective and
      prospective (observational or randomized) studies have generally shown that
      sigmoidoscopy and colonoscopy, whether for diagnostic, screening or surveillance
      purposes, are associated with a significant reduction in CRC incidence and CRC
      mortality. The data on their impact on overall mortality is much more limited,
      with most studies unable to report a reduction in overall mortality. The results
      of three meta-analyses have confirmed these conclusions. As expected,
      sigmoidoscopy has a predominant effect on left-sided CRC, although some studies
      have shown modest effects on right-sided colon cancer as well. Most studies on
      colonoscopy have demonstrated that the protective effect applies to both right
      and left-sided cancer, although the protection seemed better on the left side.
      Despite the introduction of other screening and diagnostic modalities for the
      colon, such as computed tomography colonography and colonic capsule endoscopy,
      lower endoscopy will continue to be an important mode of screening for CRC and
      evaluating the colon. 

PMID- 25374492
TI  - Would you recommend screening colonoscopy for the very elderly?
AB  - Life expectancy in Korea has increased, and the number of screening colonoscopies
      in the elderly has also dramatically increased. The net benefit of colonoscopy in
      the very elderly (>=80 years of age as defined by the World Health Organization)
      may be reduced because of the competing risk of mortality due to other diseases.
      Therefore, the decision to perform screening colonoscopy may be more complex in
      this age group. As the potential increase in life expectancy due to screening
      colonoscopy is significantly reduced in the very elderly, this procedure should
      be limited to those among the very elderly who have substantial life
      expectancies. Furthermore, considering the common major complications associated
      with colonoscopy, poor bowel preparation, and the possibility of incomplete
      colonoscopies in the very elderly, the performance of screening colonoscopy in
      the very elderly may not be an ideal recommendation. In terms of providing the
      greatest benefit to the most number of people, patients with the highest
      potential gain in terms of life expectancy, relative to the diagnostic yield,
      should be targeted for colonoscopy screening. This review addresses the unique
      considerations regarding screening colonoscopy in the very elderly and the
      individualized approach, which involves the weighing of the risks and benefits
      for each individual with consideration of their overall health status. 

PMID- 25374493
TI  - Long-term clinical outcomes of korean patient with Crohn's disease following
      early use of infliximab.
AB  - BACKGROUND/AIMS: Several recent studies have reported that the early use of
      infliximab (IFX) improves the prognosis of Crohn's disease (CD). However, no data
      are available from Asian populations, as the forementioned studies have all been
      conducted in Western countries. The aim of the current study was to evaluate the
      impact of early use of IFX on the prognosis of Korean patients with CD. METHODS:
      Patients with a diagnosis of CD established between July 1987 and January 2012
      were investigated in 12 university hospitals in Korea. Because insurance coverage
      for IFX treatment began in August 2005, patients were assigned to either of 2
      groups based on diagnosis date. The first group included patients diagnosed from
      July 1987 to December 2005, and the second from January 2006 to January 2012. We
      compared the cumulative probabilities of operation and reoperation between the
      two groups using the Kaplan-Meier method and a log-rank test. RESULTS: Of the 721
      patients investigated, 443 (61.4%) comprized the second group. Although the
      cumulative probabilities of immunosuppressant (P<0.001) and IFX use (P<0.001)
      after diagnosis were significantly higher in the second group, there were no
      significant differences in cumulative probabilities of operation (P=0.905) or
      reoperation (P=0.418) between two groups. CONCLUSIONS: The early use of IFX did
      not reduce CD-related surgery requirements in Korean patients with CD. These
      study results suggest that the early use of IFX may have little impact on the
      clinical outcome of CD in Korean patients in the setting of a conventional step
      up algorithm.

PMID- 25374494
TI  - Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's
      Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study.
AB  - BACKGROUND/AIMS: Only moderate to severe Crohn's Disease (CD) patients without a
      satisfactory conventional therapy effect are eligible to get reimbursement from
      the National Health Insurance of Taiwan for using adalimumab. These are more
      stringent criteria than in many Western countries and Japan and Korea. We aim to
      explore the efficacy of using adalimumab in CD patients under such stringent
      criteria. METHODS: A retrospective analysis was conducted in nine medical centers
      in Taiwan and we collected the results of CD patients receiving adalimumab from
      Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI
      (Crohn's Disease Activity Index), adverse events and survival status were
      recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI
      decrease of 70, 100 or 150 points compared with baseline. RESULTS: A total of 103
      CD patient records were used in this study. Sixty percent of these patients
      received combination therapy of adalimumab together with immunomodulators. CR-70
      was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The
      steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of
      patients, respectively. In considering the mucosal healing, only 25% patients
      achieve mucosal healing after treatment for 6 to 12 months. Surgery was still
      needed in 16.5% of patients. Combination treatment of adalimumab with
      immunomodulators further decreased the level of CDAI at week 8 when compared with
      the monotherapy. CONCLUSIONS: Even under the stringent criteria for using
      adalimumab, the response rate was comparable to those without stringent criteria.

PMID- 25374495
TI  - Does carotid intima-media thickness increase in patients with inflammatory bowel
      disease?
AB  - BACKGROUND/AIMS: Mesenteric microvascular thrombosis has been implicated as a
      contributing factor to the pathogenesis of inflammatory bowel disease (IBD). The
      aim of the current study was to assess the possibility of subclinical
      atherosclerosis in patients with IBD by measuring their carotid intima-media
      thickness (c-IMT). METHODS: Thirty-eight patients with IBD who were followed-up
      for at least 3 years participated. Patients with a history of cardiovascular
      disease and known risk factors for atherosclerosis were excluded. As a control
      group, 38 healthy patients matched for age and gender without atherosclerosis
      risk factors were included. Carotid ultrasonography was performed in all patients
      and controls. Patient baseline characteristics and laboratory parameters were
      recorded to evaluate atherosclerosis risk factors. RESULTS: The mean age of
      patients with IBD was 38.5+/-6.62 years. Twenty-three patients with IBD were
      diagnosed with ulcerative colitis and the other 15 cases were diagnosed with
      Crohn's disease. The median duration of disease was 52.0 months. Serologic
      markers such as erythrocyte sedimentation rate, C-reactive protein (CRP), and
      cholesterol levels differed significantly, however, there was no significant
      difference in c-IMT between patients with IBD and those in the control group
      (0.53+/-0.10 mm vs. 0.53+/-0.07; P=0.85). Multivariate analysis revealed that
      body mass index, CRP, disease duration, and age were significantly correlated
      with c-IMT in patients with IBD. CONCLUSIONS: The results of the current study
      did not show an increase in c-IMT in patients with IBD. Further studies that
      include more subjects and a longer follow-up period will be necessary in order to
      evaluate the risk of atherosclerosis in Korean patients with IBD.

PMID- 25374496
TI  - Long-Term Clinical Outcome of Clostridium difficile Infection in Hospitalized
      Patients: A Single Center Study.
AB  - BACKGROUND/AIMS: Antibiotic usage and increasingly aging populations have led to
      increased incidence of Clostridium difficile infection (CDI) in worldwide. Recent
      studies in Korea have also reported increasing CDI incidence; however, there have
      been no reports on the long-term outcomes of CDI. We therefore investigated the
      long-term clinical outcomes of patients with CDI, including delayed recurrence,
      associated risk factors and mortality. METHODS: Hospitalized patients diagnosed
      with CDI at Seoul Paik Hospital between January 2007 and December 2008 were
      included. Their medical records were retrospectively investigated. 'Delayed
      recurrence' was defined as a relapse 8 weeks after a successful initial
      treatment. Multivariate logistic regression analysis was performed to identify
      risk factors for the delayed recurrence. Kaplan-Meier curves were used to analyze
      mortality rates. RESULTS: A total of 120 patients were enrolled; among them, 87
      were followed-up for at least 1 year, with a mean follow-up period of 34.1+/-25.1
      months. Delayed recurrence was observed in 17 patients (19.5%), and significant
      risk factors were age (over 70 years, P=0.049), nasogastric tube insertion
      (P=0.008), and proton pump inhibitor or H2-blocker treatments (P=0.028). The 12-
      and 24-month mortality rates were 24.6% and 32.5%, respectively. No deaths were
      directly attributed to CDI. CONCLUSIONS: Delayed recurrence of CDI was not rare,
      occurring in 19.5% of the study population. Although CDI-related mortality was
      not reported, 2-year (32.5%) mortality rate of CDI patients implies that a CDI
      diagnosis may predict severe morbidity and poor prognosis of the underlying
      disease.

PMID- 25374497
TI  - Is the environment of the endoscopy unit a reservoir of pathogens?
AB  - BACKGROUND/AIMS: Given the characteristic procedures involved in the endoscopy
      unit, the spread of pathogens is much more frequent in this unit than in other
      environments. However, there is a lack of data elucidating the existence of
      pathogens in the endoscopy unit. The aim of this study was to detect the presence
      of possible pathogens in the endoscopy unit. METHODS: We performed environmental
      culture using samples from the endoscopy rooms of 2 tertiary hospitals. We used
      sterile cotton-tipped swabs moistened with sterile saline to swab the surfaces of
      197 samples. Then, we cultured the swab in blood agar plate. Samples from the
      colonoscopy room were placed in thioglycollate broth to detect the presence of
      anaerobes. After 2 weeks of culture period, we counted the colony numbers.
      RESULTS: The most commonly contaminated spots were the doctor's keyboard, nurse's
      cart, and nurse's mouse. The common organisms found were non-pathogenic bacterial
      microorganisms Staphylococcus, Micrococcus, and Streptococcus spp.. No definite
      anaerobe organism was detected in the colonoscopy room. CONCLUSIONS: Although the
      organisms detected in the endoscopy unit were mainly non-pathogenic organisms,
      they might cause opportunistic infections in immunocompromised patients.
      Therefore, the environment of the endoscopy room should be managed appropriately;
      moreover, individual hand hygiene is important for preventing possible hospital
      acquired infections.

PMID- 25374498
TI  - Double-balloon enteroscopy in elderly patients: is it safe and useful?
AB  - BACKGROUND/AIMS: Providers may be hesitant to perform double-balloon enteroscopy
      (DBE) in the elderly because the increased number of co-morbidities in this
      population poses a greater risk of complications resulting from sedation. There
      are limited data on the use of DBE in the elderly. Here, we assessed the safety
      and efficacy of DBE in the elderly compared to those in younger patients.
      METHODS: We retrospectively analyzed the medical records of 158 patients who
      underwent 218 DBEs. Patients were divided into an elderly group (age >=65 years;
      mean 71.4+/-5.4; n=34; 41 DBEs) and a younger group (age <65 years; mean 39.5+/
      13.5; n=124; 177 DBEs). RESULTS: In both groups, the most common indication for
      DBE was obscure gastrointestinal bleeding. Mucosal lesions (33.3% vs. 60.9%;
      P=0.002) were the most common finding in both groups, followed by tumors (30.8%
      vs. 14.1%; P=0.036). The elderly were more likely to receive interventional
      therapy (51.3% vs. 23.5%; P=0.001). The diagnostic yield of DBE was slightly
      higher in the elderly group (92.3% vs. 86.5%; P=0.422), but was not statistically
      significant. The therapeutic success rate of DBE was 100% in the elderly group
      compared to 87.5% in the younger group (P=0.536). The overall DBE complication
      rate was 1.8% overall, and this rate did not differ significantly between the
      groups (2.6% vs. 1.7%; P=0.548). CONCLUSIONS: DBE is safe and effective in the
      elderly, and has a high diagnostic yield and high therapeutic success rate.

PMID- 25374499
TI  - Polyp Clearance via Operative and Endoscopic Polypectomy in Patients With Peutz
      Jeghers Syndrome After Multiple Small Bowel Resections.
AB  - Peutz-Jeghers syndrome is an autosomal dominant inherited disease that manifests
      as a combination of mucocutaneous pigmentation and gastrointestinal hamartomatous
      polyps that usually cause intussusception and intestinal hemorrhage. We report
      the case of a 40-year-old male patient who was diagnosed 20 years ago and had
      previously undergone 3 intestinal resection surgeries. This time, with the use of
      combined operative and endoscopic polypectomy, more than 100 polyps were removed.
      This technique is useful for providing a "clean" small intestine that allows the
      patient a long interval between laparotomies and reduces the complications
      associated with multiple laparotomies and resections. 

PMID- 25374501
TI  - Can Fecaloma be Dissolved by Cola Injection in a Similar Way to Bezoars?

PMID- 25374500
TI  - Adenocarcinoma originating from a completely isolated duplication cyst of the
      mesentery in an adult.
AB  - Alimentary tract duplications are uncommon congenital abnormalities that usually
      have an anatomical connection with some part of the gastrointestinal tract and
      have a common blood supply with the adjacent segment of intestine. A completely
      isolated duplication cyst (CIDC) is a very rare type of gastrointestinal
      duplication that does not communicate with the normal bowel segment and possesses
      its own exclusive blood supply. Only 5 CIDC cases in adults have been reported in
      the English medical literature. Additionally, only 1 case of mucinous cystadenoma
      from an infected CIDC of the ileum has been reported. This report describes a 52
      year-old male patient with a peritoneal CIDC, which upon curative excision was
      found to have given rise to an adenocarcinoma. The latter was lined internally
      with malignant glandular cells and contained a smooth muscular outer layer as
      determined by microscopic examination of the tissue. We believe that this is the
      first reported case of an adenocarcinoma originating from a CIDC in an adult. 

PMID- 25374502
TI  - Radiation exposure and functional gastrointestinal disease.

PMID- 25374503
TI  - Neural dynamics implement a flexible decision bound with a fixed firing rate for
      choice: a model-based hypothesis.
AB  - Decisions are faster and less accurate when conditions favor speed, and are
      slower and more accurate when they favor accuracy. This speed-accuracy trade-off
      (SAT) can be explained by the principles of bounded integration, where noisy
      evidence is integrated until it reaches a bound. Higher bounds reduce the impact
      of noise by increasing integration times, supporting higher accuracy (vice versa
      for speed). These computations are hypothesized to be implemented by feedback
      inhibition between neural populations selective for the decision alternatives,
      each of which corresponds to an attractor in the space of network states. Since
      decision-correlated neural activity typically reaches a fixed rate at the time of
      commitment to a choice, it has been hypothesized that the neural implementation
      of the bound is fixed, and that the SAT is supported by a common input to the
      populations integrating evidence. According to this hypothesis, a stronger common
      input reduces the difference between a baseline firing rate and a threshold rate
      for enacting a choice. In simulations of a two-choice decision task, we use a
      reduced version of a biophysically-based network model (Wong and Wang, 2006) to
      show that a common input can control the SAT, but that changes to the threshold
      baseline difference are epiphenomenal. Rather, the SAT is controlled by changes
      to network dynamics. A stronger common input decreases the model's effective time
      constant of integration and changes the shape of the attractor landscape, so the
      initial state is in a more error-prone position. Thus, a stronger common input
      reduces decision time and lowers accuracy. The change in dynamics also renders
      firing rates higher under speed conditions at the time that an ideal observer can
      make a decision from network activity. The difference between this rate and the
      baseline rate is actually greater under speed conditions than accuracy
      conditions, suggesting that the bound is not implemented by firing rates per se. 

PMID- 25374505
TI  - The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap
      junctional communication in astrocytes.
AB  - In the brain, astrocytes represent the cellular population that expresses the
      highest amount of connexins (Cxs). This family of membrane proteins is the
      molecular constituent of gap junction channels and hemichannels that provide
      pathways for direct cytoplasm-to-cytoplasm and inside-out exchange, respectively.
      Both types of Cx channels are permeable to ions and small signaling molecules
      allowing astrocytes to establish dynamic interactions with neurons. So far, most
      pharmacological approaches currently available do not distinguish between these
      two channel functions, stressing the need to develop new specific molecular
      tools. In astrocytes two major Cxs are expressed, Cx43 and Cx30, and there is now
      evidence indicating that at least Cx43 operates as a gap junction channel as well
      as a hemichannel in these cells. Based on studies in primary cultures as well as
      in acute hippocampal slices, we report here that Gap19, a nonapeptide derived
      from the cytoplasmic loop of Cx43, inhibits astroglial Cx43 hemichannels in a
      dose-dependent manner, without affecting gap junction channels. This peptide,
      which not only selectively inhibits hemichannels but is also specific for Cx43,
      can be delivered in vivo in mice as TAT-Gap19, and displays penetration into the
      brain parenchyma. As a result, Gap19 combined with other tools opens up new
      avenues to decipher the role of Cx43 hemichannels in interactions between
      astrocytes and neurons in physiological as well as pathological situations. 

PMID- 25374504
TI  - Axon growth inhibition by RhoA/ROCK in the central nervous system.
AB  - Rho kinase (ROCK) is a serine/threonine kinase and a downstream target of the
      small GTPase Rho. The RhoA/ROCK pathway is associated with various neuronal
      functions such as migration, dendrite development, and axonal extension. Evidence
      from animal studies reveals that RhoA/ROCK signaling is involved in various
      central nervous system (CNS) diseases, including optic nerve and spinal cord
      injuries, stroke, and neurodegenerative diseases. Given that RhoA/ROCK plays a
      critical role in the pathophysiology of CNS diseases, the development of
      therapeutic agents targeting this pathway is expected to contribute to the
      treatment of CNS diseases. The RhoA/ROCK pathway mediates the effects of myelin
      associated axon growth inhibitors-Nogo, myelin-associated glycoprotein (MAG),
      oligodendrocyte-myelin glycoprotein (OMgp), and repulsive guidance molecule
      (RGM). Blocking RhoA/ROCK signaling can reverse the inhibitory effects of these
      molecules on axon outgrowth, and promotes axonal sprouting and functional
      recovery in animal models of CNS injury. To date, several RhoA/ROCK inhibitors
      have been under development or in clinical trials as therapeutic agents for
      neurological disorders. In this review, we focus on the RhoA/ROCK signaling
      pathway in neurological disorders. We also discuss the potential therapeutic
      approaches of RhoA/ROCK inhibitors for various neurological disorders. 

PMID- 25374506
TI  - Fate of graft cells: what should be clarified for development of mesenchymal stem
      cell therapy for ischemic stroke?
AB  - Mesenchymal stem cells (MSCs) are believed to be promising for cell
      administration therapy after ischemic stroke. Because of their advantageous
      characteristics, such as ability of differentiation into neurovascular lineages,
      avoidance of immunological problems, and abundance of graft cells in mesodermal
      tissues, studies regarding MSC therapy have increased recently. However, several
      controversies are yet to be resolved before a worldwide consensus regarding a
      standard protocol is obtained. In particular, the neuroprotective effects, the
      rate of cell migration to the lesion, and differentiation direction differ
      depending on preclinical observations. Analyses of these differences and
      application of recent developments in stem cell biology or engineering in imaging
      modality may contribute to identification of criteria for optimal stem cell
      therapy in which reliable protocols, which control cell quality and include safe
      administration procedures, are defined for each recovery phase after cerebral
      ischemia. In this mini review, we examine controversies regarding the fate of
      grafts and the prospects for advanced therapy that could be obtained through
      recent developments in stem cell research as direct conversion to neural cells. 

PMID- 25374507
TI  - Increases in intracellular calcium via activation of potentially multiple
      phospholipase C isozymes in mouse olfactory neurons.
AB  - Phospholipase C (PLC) and internal Ca(2+) stores are involved in a variety of
      cellular functions. However, our understanding of PLC in mammalian olfactory
      sensory neurons (OSNs) is generally limited to its controversial role in odor
      transduction. Here we employed single-cell Ca(2+) imaging and molecular
      approaches to investigate PLC-mediated Ca(2+) responses and its isozyme gene
      transcript expression. We found that the pan-PLC activator m-3M3FBS (25 MUM)
      induces intracellular Ca(2+) increases in vast majority of isolated mouse OSNs
      tested. Both the response amplitude and percent responding cells depend on m
      3M3FBS concentrations. In contrast, the inactive analog o-3M3FBS fails to induce
      Ca(2+) responses. The m-3M3FBS-induced Ca(2+) increase is blocked by the PLC
      inhibitor U73122, while its inactive analog U73433 has no effect. Removal of
      extracellular Ca(2+) does not change significantly the m-3M3FBS-induced Ca(2+)
      response amplitude. Additionally, in the absence of external Ca(2+), we found
      that a subset of OSNs respond to an odorant mixture with small Ca(2+) increases,
      which are significantly suppressed by U73122. Furthermore, using reverse
      transcription polymerase chain reaction and real-time quantitative polymerase
      chain reaction, we found that multiple PLC isozyme gene transcripts are expressed
      in olfactory turbinate tissue in various levels. Using RNA in situ hybridization
      analysis, we further show expression of beta4, gamma1, gamma2 gene transcripts in
      OSNs. Taken together, our results establish that PLC isozymes are potent enzymes
      for mobilizing intracellular Ca(2+) in mouse OSNs and provide molecular insight
      for PLC isozymes-mediated complex cell signaling and regulation in the peripheral
      olfactory epithelium. 

PMID- 25374508
TI  - Valproic acid potentiates curcumin-mediated neuroprotection in lipopolysaccharide
      induced rats.
AB  - The etiology of neuroinflammation is complex and comprises multifactorial,
      involving both genetic and environmental factors during which diverse genetic and
      epigenetic modulations are implicated. Curcumin (Cur) and valproic acid (VPA),
      histone deacetylase 1 inhibitor, have neuroprotective effects. The present study
      was designed with an aim to investigate the ability of co-treatment of both
      compounds (Cur or VPA, 200 mg/kg) for 4 weeks to augment neuroprotection and
      enhance brain recovery from intra-peritoneal injection of (250 MUg/kg)
      lipopolysaccharide-stimulated neuroinflammatory condition on rat brain cortex.
      Cortex activation and the effects of combined treatment and production of
      proinflammatory mediators, cyclooxygenase-2 (COX-2), APE1, and nitric
      oxide/inducible nitric oxide synthase (iNOS) were investigated. Neuroinflammation
      development was assessed by histological analyses and by investigating associated
      indices [beta-secretase (BACE1), amyloid protein precursor (APP), presenilin
      (PSEN-1), and PSEN-2)]. Furthermore we measured the expression profile of lethal
      7 (let-7) miRNAs members a, b, c, e, and f in all groups, a highly abundant
      regulator of gene expression in the CNS. Protein and mRNA levels of
      neuroinflammation markers COX-2, BACE1, APP, and iNOS were also attenuated by
      combined therapy. On the other hand, assessment of the indicated five let-7
      members, showed distinct expression profile pattern in the different groups. Let
      7 a, b, and c disappeared in the induced group, an effect that was partially
      suppressed by co-addition of either Cur or VPA. These data suggest that the
      combined treatment induced significantly the expression of the five members when
      compared to rats treated with Cur or VPA only as well as to self-recovery group,
      which indicates a possible benefit from the synergistic effect of Cur-VPA
      combination as therapeutic agents for neuroinflammation and its associated
      disorders. The mechanism elucidated here highlights the particular drug-induced
      expression profile of let-7 family as new targets for future pharmacological
      development. 

PMID- 25374509
TI  - Effects of neural progenitor cells on post-stroke neurological impairment-a
      detailed and comprehensive analysis of behavioral tests.
AB  - Systemic transplantation of neural progenitor cells (NPCs) in rodents reduces
      functional impairment after cerebral ischemia. In light of upcoming stroke trials
      regarding safety and feasibility of NPC transplantation, experimental studies
      have to successfully analyze the extent of NPC-induced neurorestoration on the
      functional level. However, appropriate behavioral tests for analysis of post
      stroke motor coordination deficits and cognitive impairment after NPC grafting
      are not fully established. We therefore exposed male C57BL6 mice to either 45 min
      (mild) or 90 min (severe) of cerebral ischemia, using the thread occlusion model
      followed by intravenous injection of PBS or NPCs 6 h post-stroke with an
      observation period of three months. Post-stroke motor coordination was assessed
      by means of the rota rod, tight rope, corner turn, inclined plane, grip strength,
      foot fault, adhesive removal, pole test and balance beam test, whereas cognitive
      impairment was analyzed using the water maze, the open field and the passive
      avoidance test. Significant motor coordination differences after both mild and
      severe cerebral ischemia in favor of NPC-treated mice were observed for each
      motor coordination test except for the inclined plane and the grip strength test,
      which only showed significant differences after severe cerebral ischemia.
      Cognitive impairment after mild cerebral ischemia was successfully assessed using
      the water maze test, the open field and the passive avoidance test. On the
      contrary, the water maze test was not suitable in the severe cerebral ischemia
      paradigm, as it too much depends on motor coordination capabilities of test mice.
      In terms of both reliability and cost-effectiveness considerations, we thus
      recommend the corner turn, foot fault, balance beam, and open field test, which
      do not depend on durations of cerebral ischemia. 

PMID- 25374510
TI  - Nanobodies as modulators of inflammation: potential applications for acute brain
      injury.
AB  - Nanobodies are single domain antibodies derived from llama heavy-chain only
      antibodies (HCAbs). They represent a new generation of biologicals with unique
      properties: nanobodies show excellent tissue distribution, high temperature and
      pH stability, are easy to produce recombinantly and can readily be converted into
      different formats such as Fc-fusion proteins or hetero-dimers. Moreover,
      nanobodies have the unique ability to bind molecular clefts, such as the active
      site of enzymes, thereby interfering with the function of the target protein.
      Over the last decade, numerous nanobodies have been developed against proteins
      involved in inflammation with the aim to modulate their immune functions. Here,
      we give an overview about recently developed nanobodies that target immunological
      pathways linked to neuroinflammation. Furthermore, we highlight strategies to
      modify nanobodies so that they can overcome the blood brain barrier and serve as
      highly specific therapeutics for acute inflammatory brain injury. 

PMID- 25374511
TI  - Compensatory Motor Neuron Response to Chromatolysis in the Murine hSOD1(G93A)
      Model of Amyotrophic Lateral Sclerosis.
AB  - We investigated neuronal self-defense mechanisms in a murine model of amyotrophic
      lateral sclerosis (ALS), the transgenic hSOD1(G93A), during both the asymptomatic
      and symptomatic stages. This is an experimental model of endoplasmic reticulum
      (ER) stress with severe chromatolysis. As a compensatory response to translation
      inhibition, chromatolytic neurons tended to reorganize the protein synthesis
      machinery at the perinuclear region, preferentially at nuclear infolding domains
      enriched in nuclear pores. This organization could facilitate nucleo-cytoplasmic
      traffic of RNAs and proteins at translation sites. By electron microscopy
      analysis, we observed that the active euchromatin pattern and the reticulated
      nucleolar configuration of control motor neurons were preserved in ALS
      chromatolytic neurons. Moreover the 5'-fluorouridine (5'-FU) transcription assay,
      at the ultrastructural level, revealed high incorporation of the RNA precursor 5'
      FU into nascent RNA. Immunogold particles of 5'-FU incorporation were distributed
      throughout the euchromatin and on the dense fibrillar component of the nucleolus
      in both control and ALS motor neurons. The high rate of rRNA transcription in ALS
      motor neurons could maintain ribosome biogenesis under conditions of severe
      dysfunction of proteostasis. Collectively, the perinuclear reorganization of
      protein synthesis machinery, the predominant euchromatin architecture, and the
      active nucleolar transcription could represent compensatory mechanisms in ALS
      motor neurons in response to the disturbance of ER proteostasis. In this
      scenario, epigenetic activation of chromatin and nucleolar transcription could
      have important therapeutic implications for neuroprotection in ALS and other
      neurodegenerative diseases. Although histone deacetylase inhibitors are currently
      used as therapeutic agents, we raise the untapped potential of the nucleolar
      transcription of ribosomal genes as an exciting new target for the therapy of
      some neurodegenerative diseases. 

PMID- 25374512
TI  - The patterning of retinal horizontal cells: normalizing the regularity index
      enhances the detection of genomic linkage.
AB  - Retinal neurons are often arranged as non-random distributions called "mosaics,"
      as their somata minimize proximity to neighboring cells of the same type. The
      horizontal cells serve as an example of such a mosaic, but little is known about
      the developmental mechanisms that underlie their patterning. To identify genes
      involved in this process, we have used three different spatial statistics to
      assess the patterning of the horizontal cell mosaic across a panel of genetically
      distinct recombinant inbred strains. To avoid the confounding effect of cell
      density, which varies twofold across these different strains, we computed the
      "real/random regularity ratio," expressing the regularity of a mosaic relative to
      a randomly distributed simulation of similarly sized cells. To test whether this
      latter statistic better reflects the variation in biological processes that
      contribute to horizontal cell spacing, we subsequently compared the genomic
      linkage for each of these two traits, the regularity index, and the real/random
      regularity ratio, each computed from the distribution of nearest neighbor (NN)
      distances and from the Voronoi domain (VD) areas. Finally, we compared each of
      these analyses with another index of patterning, the packing factor. Variation in
      the regularity indexes, as well as their real/random regularity ratios, and the
      packing factor, mapped quantitative trait loci to the distal ends of Chromosomes
      1 and 14. For the NN and VD analyses, we found that the degree of linkage was
      greater when using the real/random regularity ratio rather than the respective
      regularity index. Using informatic resources, we narrowed the list of prospective
      genes positioned at these two intervals to a small collection of six genes that
      warrant further investigation to determine their potential role in shaping the
      patterning of the horizontal cell mosaic. 

PMID- 25374513
TI  - The effects of postnatal exposure to low-dose bisphenol-A on activity-dependent
      plasticity in the mouse sensory cortex.
AB  - Bisphenol-A (BPA) is a monomer used in the production of polycarbonate plastics,
      epoxies and resins and is present in many common household objects ranging from
      water bottles, can linings, baby bottles, and dental resins. BPA exposure has
      been linked to numerous negative health effects throughout the body, although the
      mechanisms of BPA action on the developing brain are still poorly understood. In
      this study, we sought to investigate whether low dose BPA exposure during a
      developmental phase when brain connectivity is being organized can cause long
      term deleterious effects on brain function and plasticity that outlast the BPA
      exposure. Lactating dams were orally exposed to 25 MUg/kg/day of BPA (one half
      the U.S. Environmental Protection Agency's 50 MUg/kg/day rodent dose reference)
      or vehicle alone from postnatal day (P)5 to P21. Pups exposed to BPA in their
      mother's milk exhibited deficits in activity-dependent plasticity in the visual
      cortex during the visual critical period (P28). To determine the possible
      mechanisms underlying BPA action, we used immunohistochemistry to examine
      histological markers known to impact cortical maturity and developmental
      plasticity and quantified cortical dendritic spine density, morphology, and
      dynamics. While we saw no changes in parvalbumin neuron density, myelin basic
      protein expression or microglial density in BPA-exposed animals, we observed
      increases in spine density on apical dendrites in cortical layer five neurons but
      no significant alterations in other morphological parameters. Taken together our
      results suggest that exposure to very low levels of BPA during a critical period
      of brain development can have profound consequences for the normal wiring of
      sensory circuits and their plasticity later in life. 

PMID- 25374514
TI  - The contribution of hypothalamic macroglia to the regulation of energy
      homeostasis.
AB  - The hypothalamus is critical for the regulation of energy homeostasis. Genetic
      and pharmacologic studies have identified a number of key hypothalamic neuronal
      circuits that integrate signals controlling food intake and energy expenditure.
      Recently, studies have begun to emerge demonstrating a role for non-neuronal cell
      types in the regulation of energy homeostasis. In particular the potential
      importance of different glial cell types is increasingly being recognized. A
      number of studies have described changes in the activity of hypothalamic
      macroglia (principally astrocytes and tanycytes) in response to states of
      positive and negative energy balance, such as obesity and fasting. This article
      will review these studies and discuss how these findings are changing our
      understanding of the cellular mechanisms by which energy homeostasis is
      regulated. 

PMID- 25374515
TI  - Rehabilitation of homonymous hemianopia: insight into blindsight.
AB  - Strong evidence of considerable plasticity in primary sensory areas in the adult
      cortex, and of dramatic cross-modal reorganization in visual areas, after short-
      or long-term visual deprivation has recently been reported. In the context of
      patient rehabilitation, this scientifically challenging topic takes on urgent
      clinical relevance, especially given the lack of information about the role of
      such reorganization on spared or newly emerged visual performance. Amongst the
      most common visual field defects found upon unilateral occipital damage of the
      primary visual cortex is homonymous hemianopia (HH), a perfectly symmetric loss
      of vision in both eyes. Traditionally, geniculostriate lesions were considered to
      result in complete and permanent visual loss in the topographically related area
      of the visual field (Huber, 1992). However, numerous studies in monkeys, and
      later, in humans, have demonstrated that despite destruction of the striate
      cortex, or even following a hemispherectomy, some patients retain a certain
      degree of unconscious visual function, known as blindsight. Accordingly, there
      have recently been attempts to restore visual function in patients by stimulating
      unconscious preserved blindsight capacities. Herein we review different visual
      rehabilitation techniques designed for brain-damaged patients with visual field
      loss. We discuss the hypothesis that explicit (conscious) visual detection can be
      restored in the blind visual field by harnessing implicit (unconscious) visual
      capacities. The results that we summarize here underline the need for early
      diagnosis of cortical visual impairment (CVI), and the urgency in rehabilitating
      such deficits, in these patients. Based on the research precedent, we explore the
      link between implicit (unconscious) vision and conscious perception and discuss
      possible mechanisms of adaptation and plasticity in the visual cortex. 

PMID- 25374516
TI  - Unique genetic loci identified for emotional behavior in control and chronic
      stress conditions.
AB  - An individual's genetic background affects their emotional behavior and response
      to stress. Although studies have been conducted to identify genetic predictors
      for emotional behavior or stress response, it remains unknown how prior stress
      history alters the interaction between an individual's genome and their emotional
      behavior. Therefore, the purpose of this study is to identify chromosomal regions
      that affect emotional behavior and are sensitive to stress exposure. We utilized
      the BXD behavioral genetics mouse model to identify chromosomal regions that
      predict fear learning and emotional behavior following exposure to a control or
      chronic stress environment. 62 BXD recombinant inbred strains and C57BL/6 and
      DBA/2 parental strains underwent behavioral testing including a classical fear
      conditioning paradigm and the elevated plus maze. Distinct quantitative trait
      loci (QTLs) were identified for emotional learning, anxiety and locomotion in
      control and chronic stress populations. Candidate genes, including those with
      already known functions in learning and stress were found to reside within the
      identified QTLs. Our data suggest that chronic stress history reveals novel
      genetic predictors of emotional behavior. 

PMID- 25374518
TI  - Assessing complex executive functions with computerized tests: is that toast
      burning?

PMID- 25374517
TI  - In vitro extinction learning in Hermissenda: involvement of conditioned
      inhibition molecules.
AB  - Extinction of a conditioned association is typically viewed as the establishment
      of new learning rather than the erasure of the original memory. However, recent
      research in the nudibranch, Hermissenda crassicornis (H.c.) demonstrated that
      extinction training (using repeated light-alone presentations) given 15 min, but
      not 23 h, after memory acquisition reversed both the cellular correlates of
      learning (enhanced Type B cell excitability) and the behavioral changes (reduced
      phototaxis) produced by associative conditioning (pairings of light, CS, and
      rotation, US). Here, we investigated the putative molecular signaling pathways
      that underlie this extinction in H.c. by using a novel in vitro protocol combined
      with pharmacological manipulations. After intact H.c. received either light
      rotation pairings (Paired), random presentations of light and rotation (Random),
      or no stimulation (Untrained), B cells from isolated CNSs were recorded from
      during exposure to extinction training consisting of two series of 15 consecutive
      light-steps (LSs). When in vitro extinction was administered shortly (2 h, but
      not 24 h) after paired training, B cells from Paired animals showed progressive
      and robust declines in spike frequency by the 30th LS, while control cells
      (Random and Untrained) did not. We found that several molecules implicated in
      H.c. conditioned inhibitory (CI) learning, protein phosphatase 1 (PP1) and
      arachidonic acid (AA)/12-lipoxygenase (12-LOX) metabolites, also contributed to
      the spike frequency decreases produced by in vitro extinction. Protein
      phosphatase 2B (PP2B) also appeared to play a role. Calyculin A (PP1 inhibitor),
      cyclosporin A (PP2B inhibitor), and baicalein (a 12-LOX inhibitor) all blocked
      the spike frequency declines in Paired B cells produced by 30 LSs. Conversely,
      injection of catalytically-active PP1 (caPP1) or PP2B (caPP2B) into Untrained B
      cells partially mimicked the spike frequency declines observed in Paired cells,
      as did bath-applied AA, and occluded additional LS-produced reductions in spiking
      in Paired cells. 

PMID- 25374519
TI  - Cardiac autonomic functions and the emergence of violence in a highly realistic
      model of social conflict in humans.
AB  - Among the multitude of factors that can transform human social interactions into
      violent conflicts, biological features received much attention in recent years as
      correlates of decision making and aggressiveness especially in critical
      situations. We present here a highly realistic new model of human aggression and
      violence, where genuine acts of aggression are readily performed and which at the
      same time allows the parallel recording of biological concomitants. Particularly,
      we studied police officers trained at the International Training Centre
      (Budapest, Hungary), who are prepared to perform operations under extreme
      conditions of stress. We found that aggressive arousal can transform a basically
      peaceful social encounter into a violent conflict. Autonomic recordings show that
      this change is accompanied by increased heart rates, which was associated earlier
      with reduced cognitive complexity of perceptions ("attentional myopia") and
      promotes a bias toward hostile attributions and aggression. We also observed
      reduced heart rate variability in violent subjects, which is believed to signal a
      poor functioning of prefrontal-subcortical inhibitory circuits and reduces self
      control. Importantly, these autonomic particularities were observed already at
      the beginning of social encounters i.e., before aggressive acts were initiated,
      suggesting that individual characteristics of the stress-response define the way
      in which social pressure affects social behavior, particularly the way in which
      this develops into violence. Taken together, these findings suggest that cardiac
      autonomic functions are valuable external symptoms of internal motivational
      states and decision making processes, and raise the possibility that behavior
      under social pressure can be predicted by the individual characteristics of
      stress responsiveness. 

PMID- 25374520
TI  - Source-based neurofeedback methods using EEG recordings: training altered brain
      activity in a functional brain source derived from blind source separation.
AB  - A developing literature explores the use of neurofeedback in the treatment of a
      range of clinical conditions, particularly ADHD and epilepsy, whilst
      neurofeedback also provides an experimental tool for studying the functional
      significance of endogenous brain activity. A critical component of any
      neurofeedback method is the underlying physiological signal which forms the basis
      for the feedback. While the past decade has seen the emergence of fMRI-based
      protocols training spatially confined BOLD activity, traditional neurofeedback
      has utilized a small number of electrode sites on the scalp. As scalp EEG at a
      given electrode site reflects a linear mixture of activity from multiple brain
      sources and artifacts, efforts to successfully acquire some level of control over
      the signal may be confounded by these extraneous sources. Further, in the event
      of successful training, these traditional neurofeedback methods are likely
      influencing multiple brain regions and processes. The present work describes the
      use of source-based signal processing methods in EEG neurofeedback. The
      feasibility and potential utility of such methods were explored in an experiment
      training increased theta oscillatory activity in a source derived from Blind
      Source Separation (BSS) of EEG data obtained during completion of a complex
      cognitive task (spatial navigation). Learned increases in theta activity were
      observed in two of the four participants to complete 20 sessions of neurofeedback
      targeting this individually defined functional brain source. Source-based EEG
      neurofeedback methods using BSS may offer important advantages over traditional
      neurofeedback, by targeting the desired physiological signal in a more
      functionally and spatially specific manner. Having provided preliminary evidence
      of the feasibility of these methods, future work may study a range of clinically
      and experimentally relevant brain processes where individual brain sources may be
      targeted by source-based EEG neurofeedback. 

PMID- 25374521
TI  - Individual differences in beat perception affect gait responses to low- and high
      groove music.
AB  - Slowed gait in patients with Parkinson's disease (PD) can be improved when
      patients synchronize footsteps to isochronous metronome cues, but limited
      retention of such improvements suggest that permanent cueing regimes are needed
      for long-term improvements. If so, music might make permanent cueing regimes more
      pleasant, improving adherence; however, music cueing requires patients to
      synchronize movements to the "beat," which might be difficult for patients with
      PD who tend to show weak beat perception. One solution may be to use high-groove
      music, which has high beat salience that may facilitate synchronization, and
      affective properties, which may improve motivation to move. As a first step to
      understanding how beat perception affects gait in complex neurological disorders,
      we examined how beat perception ability affected gait in neurotypical adults.
      Synchronization performance and gait parameters were assessed as healthy young
      adults with strong or weak beat perception synchronized to low-groove music, high
      groove music, and metronome cues. High-groove music was predicted to elicit
      better synchronization than low-groove music, due to its higher beat salience.
      Two musical tempi, or rates, were used: (1) preferred tempo: beat rate matched to
      preferred step rate and (2) faster tempo: beat rate adjusted to 22.5% faster than
      preferred step rate. For both strong and weak beat-perceivers, synchronization
      performance was best with metronome cues, followed by high-groove music, and
      worst with low-groove music. In addition, high-groove music elicited longer and
      faster steps than low-groove music, both at preferred tempo and at faster tempo.
      Low-groove music was particularly detrimental to gait in weak beat-perceivers,
      who showed slower and shorter steps compared to uncued walking. The findings show
      that individual differences in beat perception affect gait when synchronizing
      footsteps to music, and have implications for using music in gait rehabilitation.

PMID- 25374522
TI  - Doing Duo - a case study of entrainment in William Forsythe's choreography "Duo".
AB  - Entrainment theory focuses on processes in which interacting (i.e., coupled)
      rhythmic systems stabilize, producing synchronization in the ideal sense, and
      forms of phase related rhythmic coordination in complex cases. In human action,
      entrainment involves spatiotemporal and social aspects, characterizing the
      meaningful activities of music, dance, and communication. How can the phenomenon
      of human entrainment be meaningfully studied in complex situations such as dance?
      We present an in-progress case study of entrainment in William Forsythe's
      choreography Duo, a duet in which coordinated rhythmic activity is achieved
      without an external musical beat and without touch-based interaction. Using
      concepts of entrainment from different disciplines as well as insight from Duo
      performer Riley Watts, we question definitions of entrainment in the context of
      dance. The functions of chorusing, turn-taking, complementary action, cues, and
      alignments are discussed and linked to supporting annotated video material. While
      Duo challenges the definition of entrainment in dance as coordinated response to
      an external musical or rhythmic signal, it supports the definition of entrainment
      as coordinated interplay of motion and sound production by active agents (i.e.,
      dancers) in the field. Agreeing that human entrainment should be studied on
      multiple levels, we suggest that entrainment between the dancers in Duo is
      elastic in time and propose how to test this hypothesis empirically. We do not
      claim that our proposed model of elasticity is applicable to all forms of human
      entrainment nor to all examples of entrainment in dance. Rather, we suggest
      studying higher order phase correction (the stabilizing tendency of entrainment)
      as a potential aspect to be incorporated into other models. 

PMID- 25374523
TI  - Neural processing of emotion in multimodal settings.

PMID- 25374524
TI  - Motor output variability, deafferentation, and putative deficits in kinesthetic
      reafference in Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder defined by motor
      impairments that include rigidity, systemic slowdown of movement (bradykinesia),
      postural problems, and tremor. While the progressive decline in motor output
      functions is well documented, less understood are impairments linked to the
      continuous kinesthetic sensation emerging from the flow of motions. There is
      growing evidence in recent years that kinesthetic problems are also part of the
      symptoms of PD, but objective methods to readily quantify continuously unfolding
      motions across different contexts have been lacking. Here we present evidence
      from a deafferented subject (IW) and a new statistical platform that enables new
      analyses of motor output variability measured as a continuous flow of kinesthetic
      reafferent input. Systematic increasing similarities between the patterns of
      motor output variability in IW and the participants with increasing degrees of PD
      severity suggest potential deficits in kinesthetic sensing in PD. We propose that
      these deficits may result from persistent, noisy, and random motor patterns as
      the disorder progresses. The stochastic signatures from the unfolding motions
      revealed levels of noise in the motor output fluctuations of these patients bound
      to decrease the kinesthetic signal's bandwidth. The results are interpreted in
      light of the concept of kinesthetic reafference ( Von Holst and Mittelstaedt,
      1950). In this context, noisy motor output variability from voluntary movements
      in PD leads to a returning stream of noisy afference caused, in turn, by those
      faulty movements themselves. Faulty efferent output re-enters the CNS as
      corrupted sensory motor input. We find here that severity level in PD leads to
      the persistence of such patterns, thus bringing the statistical signatures of the
      subjects with PD systematically closer to those of the subject without
      proprioception. 

PMID- 25374525
TI  - Is there a neuroanatomical basis of the vulnerability to suicidal behavior? A
      coordinate-based meta-analysis of structural and functional MRI studies.
AB  - OBJECTIVE: We conducted meta-analyses of functional and structural neuroimaging
      studies comparing adolescent and adult individuals with a history of suicidal
      behavior and a psychiatric disorder to psychiatric controls in order to objectify
      changes in brain structure and function in association with a vulnerability to
      suicidal behavior. METHODS: Magnetic resonance imaging studies published up to
      July 2013 investigating structural or functional brain correlates of suicidal
      behavior were identified through computerized and manual literature searches.
      Activation foci from 12 studies encompassing 475 individuals, i.e., 213 suicide
      attempters and 262 psychiatric controls were subjected to meta-analytical study
      using anatomic or activation likelihood estimation (ALE). RESULT: Activation
      likelihood estimation revealed structural deficits and functional changes in
      association with a history of suicidal behavior. Structural findings included
      reduced volumes of the rectal gyrus, superior temporal gyrus and caudate nucleus.
      Functional differences between study groups included an increased reactivity of
      the anterior and posterior cingulate cortices. DISCUSSION: A history of suicidal
      behavior appears to be associated with (probably interrelated) structural
      deficits and functional overactivation in brain areas, which contribute to a
      decision-making network. The findings suggest that a vulnerability to suicidal
      behavior can be defined in terms of a reduced motivational control over the
      intentional behavioral reaction to salient negative stimuli.

PMID- 25374526
TI  - Divergent hemispheric reasoning strategies: reducing uncertainty versus resolving
      inconsistency.
AB  - Converging lines of evidence from diverse research domains suggest that the left
      and right hemispheres play distinct, yet complementary, roles in inferential
      reasoning. Here, we review research on split-brain patients, brain-damaged
      patients, delusional patients, and healthy individuals that suggests that the
      left hemisphere tends to create explanations, make inferences, and bridge gaps in
      information, while the right hemisphere tends to detect conflict, update beliefs,
      support mental set-shifts, and monitor and inhibit behavior. Based on this
      evidence, we propose that the left hemisphere specializes in creating hypotheses
      and representing causality, while the right hemisphere specializes in evaluating
      hypotheses, and rejecting those that are implausible or inconsistent with other
      evidence. In sum, we suggest that, in the domain of inferential reasoning, the
      left hemisphere strives to reduce uncertainty while the right hemisphere strives
      to resolve inconsistency. The hemispheres' divergent inferential reasoning
      strategies may contribute to flexible, complex reasoning in the healthy brain,
      and disruption in these systems may explain reasoning deficits in the unhealthy
      brain. 

PMID- 25374527
TI  - Investigating the neural bases for intra-subject cognitive efficiency changes
      using functional magnetic resonance imaging.
AB  - Several fMRI studies have examined brain regions mediating inter-subject
      variability in cognitive efficiency, but none have examined regions mediating
      intra-subject variability in efficiency. Thus, the present study was designed to
      identify brain regions involved in intra-subject variability in cognitive
      efficiency via participant-level correlations between trial-level reaction time
      (RT) and trial-level fMRI BOLD percent signal change on a processing speed task.
      On each trial, participants indicated whether a digit-symbol probe-pair was
      present or absent in an array of nine digit-symbol probe-pairs while fMRI data
      were collected. Deconvolution analyses, using RT time-series models (derived from
      the proportional scaling of an event-related hemodynamic response function model
      by trial-level RT), were used to evaluate relationships between trial-level RTs
      and BOLD percent signal change. Although task-related patterns of activation and
      deactivation were observed in regions including bilateral occipital, bilateral
      parietal, portions of the medial wall such as the precuneus, default mode network
      regions including anterior cingulate, posterior cingulate, bilateral temporal,
      right cerebellum, and right cuneus, RT-BOLD correlations were observed in a more
      circumscribed set of regions. Positive RT-BOLD correlations, where fast RTs were
      associated with lower BOLD percent signal change, were observed in regions
      including bilateral occipital, bilateral parietal, and the precuneus. RT-BOLD
      correlations were not observed in the default mode network indicating a smaller
      set of regions associated with intra-subject variability in cognitive efficiency.
      The results are discussed in terms of a distributed area of regions that mediate
      variability in the cognitive efficiency that might underlie processing speed
      differences between individuals. 

PMID- 25374528
TI  - Neurofeedback in attention-deficit/hyperactivity disorder - different models,
      different ways of application.
AB  - In children with attention-deficit/hyperactivity disorder (ADHD), different
      neurofeedback (NF) protocols have been applied, with the most prominent
      differentiation between EEG frequency-band (e.g., theta/beta) training and
      training of slow cortical potentials (SCPs). However, beyond distinctions between
      such basic NF variables, there are also competing assumptions about mechanisms of
      action (e.g., acquisition of regulation capability, generalization to daily life
      behavior). In the present article, we provide a framework for NF models and
      suppose two hypothetical models, which we call "conditioning-and-repairing model"
      and "skill-acquisition model," reflecting extreme poles within this framework. We
      argue that the underlying model has an impact not only on how NF is applied but
      also on the selection of evaluation strategies and suggest using evaluation
      strategies beyond beaten paths of pharmacological research. Reflecting available
      studies, we address to what extent different views are supported by empirical
      data. We hypothesize that different models may hold true depending on the
      processes and behaviors to be addressed by a certain NF protocol. For example,
      the skill-acquisition model is supported by recent findings as an adequate
      explanatory framework for the mechanisms of action of SCP training in ADHD. In
      conclusion, evaluation and interpretation of NF trials in ADHD should be based on
      the underlying model and the way training is applied, which, in turn, should be
      stated explicitly in study reports. 

PMID- 25374529
TI  - Emotion recognition and cognitive empathy deficits in adolescent offenders
      revealed by context-sensitive tasks.
AB  - Emotion recognition and empathy abilities require the integration of contextual
      information in real-life scenarios. Previous reports have explored these domains
      in adolescent offenders (AOs) but have not used tasks that replicate everyday
      situations. In this study we included ecological measures with different levels
      of contextual dependence to evaluate emotion recognition and empathy in AOs
      relative to non-offenders, controlling for the effect of demographic variables.
      We also explored the influence of fluid intelligence (FI) and executive functions
      (EFs) in the prediction of relevant deficits in these domains. Our results showed
      that AOs exhibit deficits in context-sensitive measures of emotion recognition
      and cognitive empathy. Difficulties in these tasks were neither explained by
      demographic variables nor predicted by FI or EFs. However, performance on
      measures that included simpler stimuli or could be solved by explicit knowledge
      was either only partially affected by demographic variables or preserved in AOs.
      These findings indicate that AOs show contextual social-cognition impairments
      which are relatively independent of basic cognitive functioning and demographic
      variables. 

PMID- 25374530
TI  - Effects of weekly low-frequency rTMS on autonomic measures in children with
      autism spectrum disorder.
AB  - The term autism spectrum disorder (ASD) describes a range of conditions
      characterized by impairments in social interactions, communication, and by
      restricted and repetitive behaviors. Autism spectrum disorder may also present
      with symptoms suggestive of autonomic nervous system (ANS) dysfunction. The
      objective of this study was to determine the effect of 18 sessions of low
      frequency (LF) repetitive transcranial magnetic stimulation (rTMS) on autonomic
      function in children with ASD by recording electrocardiogram (ECG) and
      electrodermal activity (EDA) pre- post- and during each rTMS session. The
      autonomic measures of interest in this study were R-R cardiointervals in EKG (R
      R), time and frequency domain measures of heart rate variability (HRV) and skin
      conductance level (SCL). Heart rate variability measures such as R-R intervals,
      standard deviation of cardiac intervals, pNN50 (percentage of cardiointervals >50
      ms different from preceding interval), power of high frequency (HF) and LF
      components of HRV spectrum, LF/HF ratio, were then derived from the recorded EKG.
      We expected that the course of 18 weekly inhibitory LF rTMS applied to the
      dorsolateral prefrontal cortex (DLPFC) would enhance autonomic balance by
      facilitating frontal inhibition of limbic activity thus resulting in decreased
      overall heart rate (HR), increased HRV (in a form of increased HF power),
      decreased LF power (resulting in decreased LF/HF ratio), and decreased SCL.
      Behavioral evaluations post-18 TMS showed decreased irritability, hyperactivity,
      stereotype behavior and compulsive behavior ratings while autonomic measures
      indicated a significant increase in cardiac interval variability and a decrease
      of tonic SCL. The results suggest that 18 sessions of LF rTMS in ASD results in
      increased cardiac vagal control and reduced sympathetic arousal. 

PMID- 25374532
TI  - Epidural electrocorticography for monitoring of arousal in locked-in state.
AB  - Electroencephalography (EEG) often fails to assess both the level (i.e., arousal)
      and the content (i.e., awareness) of pathologically altered consciousness in
      patients without motor responsiveness. This might be related to a decline of
      awareness, to episodes of low arousal and disturbed sleep patterns, and/or to
      distorting and attenuating effects of the skull and intermediate tissue on the
      recorded brain signals. Novel approaches are required to overcome these
      limitations. We introduced epidural electrocorticography (ECoG) for monitoring of
      cortical physiology in a late-stage amytrophic lateral sclerosis patient in
      completely locked-in state (CLIS). Despite long-term application for a period of
      six months, no implant-related complications occurred. Recordings from the left
      frontal cortex were sufficient to identify three arousal states. Spectral
      analysis of the intrinsic oscillatory activity enabled us to extract state
      dependent dominant frequencies at <4, ~7 and ~20 Hz, representing sleep-like
      periods, and phases of low and elevated arousal, respectively. In the absence of
      other biomarkers, ECoG proved to be a reliable tool for monitoring circadian
      rhythmicity, i.e., avoiding interference with the patient when he was sleeping
      and exploiting time windows of responsiveness. Moreover, the effects of
      interventions addressing the patient's arousal, e.g., amantadine medication,
      could be evaluated objectively on the basis of physiological markers, even in the
      absence of behavioral parameters. Epidural ECoG constitutes a feasible trade-off
      between surgical risk and quality of recorded brain signals to gain information
      on the patient's present level of arousal. This approach enables us to optimize
      the timing of interactions and medical interventions, all of which should take
      place when the patient is in a phase of high arousal. Furthermore, avoiding low
      responsiveness periods will facilitate measures to implement alternative
      communication pathways involving brain-computer interfaces (BCI). 

PMID- 25374531
TI  - Fetal functional imaging portrays heterogeneous development of emerging human
      brain networks.
AB  - The functional connectivity architecture of the adult human brain enables complex
      cognitive processes, and exhibits a remarkably complex structure shared across
      individuals. We are only beginning to understand its heterogeneous structure,
      ranging from a strongly hierarchical organization in sensorimotor areas to widely
      distributed networks in areas such as the parieto-frontal cortex. Our study
      relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses
      with no detectable morphological abnormalities. After adapting functional
      magnetic resonance acquisition, motion correction, and nuisance signal reduction
      procedures of resting-state functional data analysis to fetuses, we extracted
      neural activity information for major cortical and subcortical structures.
      Resting fMRI networks were observed for increasing regional functional
      connectivity from 21st to 38th gestational weeks (GWs) with a network-based
      statistical inference approach. The overall connectivity network, short range,
      and interhemispheric connections showed sigmoid expansion curve peaking at the 26
      29 GW. In contrast, long-range connections exhibited linear increase with no
      periods of peaking development. Region-specific increase of functional signal
      synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26
      GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We
      successfully adapted functional neuroimaging and image post-processing approaches
      to correlate macroscopical scale activations in the fetal brain with gestational
      age. This in vivo study reflects the fact that the mid-fetal period hosts events
      that cause the architecture of the brain circuitry to mature, which presumably
      manifests in increasing strength of intra- and interhemispheric functional macro
      connectivity. 

PMID- 25374533
TI  - The neural correlates of belief bias: activation in inferior frontal cortex
      reflects response rate differences.

PMID- 25374534
TI  - Dynamic stability of sequential stimulus representations in adapting neuronal
      networks.
AB  - The ability to acquire and maintain appropriate representations of time-varying,
      sequential stimulus events is a fundamental feature of neocortical circuits and a
      necessary first step toward more specialized information processing. The
      dynamical properties of such representations depend on the current state of the
      circuit, which is determined primarily by the ongoing, internally generated
      activity, setting the ground state from which input-specific transformations
      emerge. Here, we begin by demonstrating that timing-dependent synaptic plasticity
      mechanisms have an important role to play in the active maintenance of an ongoing
      dynamics characterized by asynchronous and irregular firing, closely resembling
      cortical activity in vivo. Incoming stimuli, acting as perturbations of the local
      balance of excitation and inhibition, require fast adaptive responses to prevent
      the development of unstable activity regimes, such as those characterized by a
      high degree of population-wide synchrony. We establish a link between such
      pathological network activity, which is circumvented by the action of plasticity,
      and a reduced computational capacity. Additionally, we demonstrate that the
      action of plasticity shapes and stabilizes the transient network states exhibited
      in the presence of sequentially presented stimulus events, allowing the
      development of adequate and discernible stimulus representations. The main
      feature responsible for the increased discriminability of stimulus-driven
      population responses in plastic networks is shown to be the decorrelating action
      of inhibitory plasticity and the consequent maintenance of the asynchronous
      irregular dynamic regime both for ongoing activity and stimulus-driven responses,
      whereas excitatory plasticity is shown to play only a marginal role. 

PMID- 25374535
TI  - Why vision is not both hierarchical and feedforward.
AB  - In classical models of object recognition, first, basic features (e.g., edges and
      lines) are analyzed by independent filters that mimic the receptive field
      profiles of V1 neurons. In a feedforward fashion, the outputs of these filters
      are fed to filters at the next processing stage, pooling information across
      several filters from the previous level, and so forth at subsequent processing
      stages. Low-level processing determines high-level processing. Information lost
      on lower stages is irretrievably lost. Models of this type have proven to be very
      successful in many fields of vision, but have failed to explain object
      recognition in general. Here, we present experiments that, first, show that,
      similar to demonstrations from the Gestaltists, figural aspects determine low
      level processing (as much as the other way around). Second, performance on a
      single element depends on all the other elements in the visual scene. Small
      changes in the overall configuration can lead to large changes in performance.
      Third, grouping of elements is key. Only if we know how elements group across the
      entire visual field, can we determine performance on individual elements, i.e.,
      challenging the classical stereotypical filtering approach, which is at the very
      heart of most vision models. 

PMID- 25374537
TI  - Spatial memory deficits in a mouse model of late-onset Alzheimer's disease are
      caused by zinc supplementation and correlate with amyloid-beta levels.
AB  - Much of the research in Alzheimer's disease (AD) that uses mouse models focuses
      on the early-onset form of the disease, which accounts for less than 5% of cases.
      In contrast, this study used a late-onset AD model to examine the interaction
      between increased dietary zinc (Zn) and the apolipoprotein E (ApoE) gene. ApoE
      epsilon4 is overrepresented in late-onset AD and enhances Zn binding to amyloid
      beta (Abeta). This study sought to determine if elevated dietary Zn would impair
      spatial memory in CRND8 mice (CRND8), as well as mice who carry both the mutated
      human amyloid precursor protein (APP) and ApoE epsilon4 genes (CRND8/E4). Mice
      were provided with either lab tap water or water enhanced with 10 ppm Zn (ZnCO3)
      for 4 months. At 6 months of age, spatial memory was measured by the Barnes maze.
      CRND8 mice exhibited significant memory deficits compared to WT mice, as shown by
      an increased latency to reach the escape box. For the CRND8/E4, but not the CRND8
      mice, those given Zn water made significantly more errors than those on lab
      water. During the probe trial for the WT group, those on Zn water spent
      significantly less time in the target quadrant than those on lab water. These
      data suggest that increased dietary Zn can significantly impair spatial memory in
      CRND8/E4. WT mice given Zn water were also impaired on the 24-h probe trial when
      compared to lab water WTs. Within the CRND8/E4 group only, levels of soluble
      Abeta were significantly correlated with average primary latencies. Within the Zn
      treated CRND8/E4 group, there was a significant correlation between insoluble
      Abeta and average primary errors. Levels of the zinc transporter 3, ZnT3, were
      negatively correlated with soluble Abeta (p < 0.01). These findings are
      particularly relevant because increased intake of dietary supplements, such as
      Zn, are common in the elderly-a population already at risk for AD. Given the
      effects observed in the CRND8/E4 mice, ApoE status should be taken into
      consideration when evaluating the efficacy of therapies targeting metals. 

PMID- 25374538
TI  - Cognition and gait show a selective pattern of association dominated by phenotype
      in incident Parkinson's disease.
AB  - Reports outlining the association between gait and cognition in Parkinson's
      disease (PD) are limited because of methodological issues and a bias toward
      studying advanced disease. This study examines the association between gait and
      cognition in 121 early PD who were characterized according to motor phenotype,
      and 184 healthy older adults. Quantitative gait was captured using a 7 m GAITrite
      walkway while walking for 2 min under single-task conditions and described by
      five domains (pace, rhythm, variability, asymmetry, and postural control).
      Cognitive outcomes were summarized by six domains (attention, working memory,
      visual memory, executive function, visuospatial function, and global cognition).
      Partial correlations and multivariate linear regression were used to determine
      independent associations for all participants and for PD tremor-dominant (TD) and
      postural instability and gait disorder (PIGD) phenotypes, controlling for age,
      sex, and premorbid intelligence using the national adult reading test. Cognitive
      and gait outcomes were significantly worse for PD. Gait, but not cognitive
      outcomes, was selectively worse for the PIGD phenotype compared with TD.
      Significant associations emerged for two gait domains for controls (pace and
      postural control) and four gait domains for PD (pace, rhythm, variability, and
      postural control). The strongest correlation was for pace and attention for PD
      and controls. Associations were not significant for participants with the TD
      phenotype. In early PD, the cognitive correlates of gait are predominantly with
      fronto-executive functions, and are characterized by the PIGD PD phenotype. These
      associations provide a basis for understanding the complex role of cognition in
      parkinsonian gait. 

PMID- 25374539
TI  - Influence of age on postural sway during different dual-task conditions.
AB  - Dual-task performance assessments of competing parallel tasks and postural
      outcomes are growing in importance for geriatricians, as it is associated with
      predicting fall risk in older adults. This study aims to evaluate the postural
      stability during different dual-task conditions including visual (SMBT), verbal
      (CBAT) and cognitive (MAT) tasks in comparison with the standard Romberg's open
      eyes position (OE). Furthermore, these conditions were investigated in a sample
      of young adults and a group of older healthy subjects to examine a potential
      interaction between type of secondary task and age status. To compare these
      groups across the four conditions, a within-between mixed model ANOVA was
      applied. Thus, a stabilometric platform has been used to measure center of
      pressure velocity (CoPV), sway area (SA), antero-posterior (AP) and medio-lateral
      (ML) oscillations as extents of postural sway. Tests of within-subjects effects
      indicated that different four conditions influenced the static balance for CoPV
      (p < 0.001), SA (p < 0.001). Post-hoc analyses indicated that CBAT task induced
      the worst balance condition on CoPV and resulted in significantly worse scores
      than OE (-11.4%; p < 0.05), SMBT (-17.8%; p < 0.01) and MAT (-17.8%; p < 0.01)
      conditions; the largest SA was found in OE, and it was statistically larger than
      SMBT (-27.0%; p < 0.01) and MAT (-23.1%; p < 0.01). The between-subjects analysis
      indicated a general lower balance control in the group of elderly subjects (CoPV
      p < 0.001, SA p < 0.002), while, the mixed model ANOVA did not detect any
      interaction effect between types of secondary task and groups in any parameters
      (CoPV p = 0.154, SA p = 0.125). Postural sway during dual-task assessments was
      also found to decrease with advancing age, however, no interactions between aging
      and types of secondary tasks were found. Overall, these results indicated that
      the secondary task which most influenced the length of sway path, as measured by
      postural stability was a simple verbal assignment. 

PMID- 25374540
TI  - Biomarkers in neurodegenerative disorders: translating research into clinical
      practice.

PMID- 25374541
TI  - A computer-based quantitative systems pharmacology model of negative symptoms in
      schizophrenia: exploring glycine modulation of excitation-inhibition balance.
AB  - Although many antipsychotics can reasonably control positive symptoms in
      schizophrenia, patients' return to society is often hindered by negative symptoms
      and cognitive deficits. As an alternative to animal rodent models that are often
      not very predictive for the clinical situation, we developed a new computer-based
      mechanistic modeling approach. This Quantitative Systems Pharmacology approach
      combines preclinical basic neurophysiology of a biophysically realistic neuronal
      ventromedial cortical-ventral striatal network identified from human imaging
      studies that are associated with negative symptoms. Calibration of a few
      biological coupling parameters using a retrospective clinical database of 34 drug
      dose combinations resulted in correlation coefficients greater than 0.60, while a
      robust quantitative prediction of a number of independent trials was observed. We
      then simulated the effect of glycine modulation on the anticipated clinical
      outcomes. The quantitative biochemistry of glycine interaction with the different
      NMDA-NR2 subunits, neurodevelopmental trajectory of the NMDA-NR2B in the human
      schizophrenia pathology, their specific localization on excitatory vs. inhibitory
      interneurons and the electrogenic nature of the glycine transporter resulted in
      an inverse U-shape dose-response with an optimum in the low micromolar glycine
      concentration. Quantitative systems pharmacology based computer modeling of
      complex humanized brain circuits is a powerful alternative approach to explain
      the non-monotonic dose-response observed in past clinical trial outcomes with
      sarcosine, D-cycloserine, glycine, or D-serine or with glycine transporter
      inhibitors. In general it can be helpful to better understand the human
      neurophysiology of negative symptoms, especially with targets that show non
      monotonic dose-responses. 

PMID- 25374536
TI  - Striatal cholinergic interneuron regulation and circuit effects.
AB  - The striatum plays a central role in motor control and motor learning.
      Appropriate responses to environmental stimuli, including pursuit of reward or
      avoidance of aversive experience all require functional striatal circuits. These
      pathways integrate synaptic inputs from limbic and cortical regions including
      sensory, motor and motivational information to ultimately connect intention to
      action. Although many neurotransmitters participate in striatal circuitry, one
      critically important player is acetylcholine (ACh). Relative to other brain
      areas, the striatum contains exceptionally high levels of ACh, the enzymes that
      catalyze its synthesis and breakdown, as well as both nicotinic and muscarinic
      receptor types that mediate its postsynaptic effects. The principal source of
      striatal ACh is the cholinergic interneuron (ChI), which comprises only about 1
      2% of all striatal cells yet sends dense arbors of projections throughout the
      striatum. This review summarizes recent advances in our understanding of the
      factors affecting the excitability of these neurons through acute effects and
      long term changes in their synaptic inputs. In addition, we discuss the
      physiological effects of ACh in the striatum, and how changes in ACh levels may
      contribute to disease states during striatal dysfunction. 

PMID- 25374542
TI  - Virtual Systems Pharmacology (ViSP) software for simulation from mechanistic
      systems-level models.
AB  - Multiple software programs are available for designing and running large scale
      system-level pharmacology models used in the drug development process. Depending
      on the problem, scientists may be forced to use several modeling tools that could
      increase model development time, IT costs and so on. Therefore, it is desirable
      to have a single platform that allows setting up and running large-scale
      simulations for the models that have been developed with different modeling
      tools. We developed a workflow and a software platform in which a model file is
      compiled into a self-contained executable that is no longer dependent on the
      software that was used to create the model. At the same time the full model
      specifics is preserved by presenting all model parameters as input parameters for
      the executable. This platform was implemented as a model agnostic, therapeutic
      area agnostic and web-based application with a database back-end that can be used
      to configure, manage and execute large-scale simulations for multiple models by
      multiple users. The user interface is designed to be easily configurable to
      reflect the specifics of the model and the user's particular needs and the back
      end database has been implemented to store and manage all aspects of the systems,
      such as Models, Virtual Patients, User Interface Settings, and Results. The
      platform can be adapted and deployed on an existing cluster or cloud computing
      environment. Its use was demonstrated with a metabolic disease systems
      pharmacology model that simulates the effects of two antidiabetic drugs,
      metformin and fasiglifam, in type 2 diabetes mellitus patients. 

PMID- 25374543
TI  - Preserved frontal lobe oxygenation following calcium chloride for treatment of
      anesthesia-induced hypotension.
AB  - Vasopressor agents may affect cerebral oxygenation (rScO2) as determined by near
      infrared spectroscopy on the forehead. This case series evaluated the effect of
      calcium chloride vs. alpha and beta-adrenergic receptor agonists on rScO2 in
      patients (n = 47) undergoing surgery during i.v. anesthesia. Mean arterial
      pressure (MAP) and cardiac output (CO) were assessed by Model-flow((r)) and
      ephedrine (55 +/- 3 vs. 74 +/- 9 mmHg; 10 mg, n = 9), phenylephrine (51 +/- 5 vs.
      78 +/- 9 mmHg, 0.1 mg, n = 11), adrenaline (53 +/- 3 vs. 72 +/- 11 mmHg; 1-2 MUg,
      n = 6), noradrenaline (53 +/- 5 vs. 72 +/- 12 mmHg; 2-4 MUg, n = 11), and calcium
      chloride (49 +/- 7 vs. 57 +/- 16 mmHg; 5 mmol, n = 10) increased MAP (all P <
      0.05). CO increased with ephedrine (4.3 +/- 0.9 vs. 5.3 +/- 1.2, P < 0.05) and
      adrenaline (4.7 +/- 1.2 vs. 5.9 +/- 1.1 l/min; P = 0.07) but was not
      significantly affected by phenylephrine (3.9 +/- 0.7 vs. 3.6 +/- 1.0 l/min),
      noradrenaline (3.8 +/- 1.2 vs. 3.7 +/- 0.7 l/min), or calcium chloride (4.0 +/-
      1.4 vs. 4.1 +/- 1.5 l/min). Following administration of beta-adrenergic agents
      and calcium chloride rScO2 was preserved while after administration of alpha
      adrenergic drugs rScO2 was reduced by app. 2% (P < 0.05). Following alpha
      adrenergic drugs to treat anesthesia-induced hypotension tissue oxygenation is
      reduced while the use of beta-adrenergic agonists and calcium chloride preserve
      tissue oxygenation. 

PMID- 25374545
TI  - Double jeopardy in inferring cognitive processes.
AB  - Inferences we make about underlying cognitive processes can be jeopardized in two
      ways due to problematic forms of aggregation. First, averaging across individuals
      is typically considered a very useful tool for removing random variability. The
      threat is that averaging across subjects leads to averaging across different
      cognitive strategies, thus harming our inferences. The second threat comes from
      the construction of inadequate research designs possessing a low diagnostic
      accuracy of cognitive processes. For that reason we introduced the systems
      factorial technology (SFT), which has primarily been designed to make inferences
      about underlying processing order (serial, parallel, coactive), stopping rule
      (terminating, exhaustive), and process dependency. SFT proposes that the minimal
      research design complexity to learn about n number of cognitive processes should
      be equal to 2 (n) . In addition, SFT proposes that (a) each cognitive process
      should be controlled by a separate experimental factor, and (b) The saliency
      levels of all factors should be combined in a full factorial design. In the
      current study, the author cross combined the levels of jeopardies in a 2 * 2
      analysis, leading to four different analysis conditions. The results indicate a
      decline in the diagnostic accuracy of inferences made about cognitive processes
      due to the presence of each jeopardy in isolation and when combined. The results
      warrant the development of more individual subject analyses and the utilization
      of full-factorial (SFT) experimental designs. 

PMID- 25374546
TI  - The role of predictability and structure in word stress processing: an ERP study
      on Cairene Arabic and a cross-linguistic comparison.
AB  - This article presents neurolinguistic data on word stress perception in Cairene
      Arabic, in comparison to previous results on German and Turkish. The main goal is
      to investigate how central properties of stress systems such as predictability of
      stress and metrical structure are reflected in the prosodic processing of words.
      Cairene Arabic is a language with a regular foot-based word stress system,
      leading to highly predictable placement of word stress. An ERP study on Cairene
      Arabic is reported, in which a stress violation paradigm is used to investigate
      the factors predictability of stress and foot structure. The results of the
      experiment show that for Cairene Arabic the internal structure of prosodic words
      in terms of feet determines prosodic processing. This structure effect is
      complemented by a frequency effect for stress patterns. 

PMID- 25374544
TI  - Investigating developmental cardiovascular biomechanics and the origins of
      congenital heart defects.
AB  - Innovative research on the interactions between biomechanical load and
      cardiovascular (CV) morphogenesis by multiple investigators over the past 3
      decades, including the application of bioengineering approaches, has shown that
      the embryonic heart adapts both structure and function in order to maintain
      cardiac output to the rapidly growing embryo. Acute adaptive hemodynamic
      mechanisms in the embryo include the redistribution of blood flow within the
      heart, dynamic adjustments in heart rate and developed pressure, and beat to beat
      variations in blood flow and vascular resistance. These biomechanically relevant
      events occur coincident with adaptive changes in gene expression and trigger
      adaptive mechanisms that include alterations in myocardial cell growth and death,
      regional and global changes in myocardial architecture, and alterations in
      central vascular morphogenesis and remodeling. These adaptive mechanisms allow
      the embryo to survive these biomechanical stresses (environmental, maternal) and
      to compensate for developmental errors (genetic). Recent work from numerous
      laboratories shows that a subset of these adaptive mechanisms is present in every
      developing multicellular organism with a "heart" equivalent structure. This
      chapter will provide the reader with an overview of some of the approaches used
      to quantify embryonic CV functional maturation and performance, provide several
      illustrations of experimental interventions that explore the role of biomechanics
      in the regulation of CV morphogenesis including the role of computational
      modeling, and identify several critical areas for future investigation as
      available experimental models and methods expand. 

PMID- 25374547
TI  - Between-domain relations of students' academic emotions and their judgments of
      school domain similarity.
AB  - With the aim to deepen our understanding of the between-domain relations of
      academic emotions, a series of three studies was conducted. We theorized that
      between-domain relations of trait (i.e., habitual) emotions reflected students'
      judgments of domain similarities, whereas between-domain relations of state
      (i.e., momentary) emotions did not. This supposition was based on the
      accessibility model of emotional self-report, according to which individuals'
      beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1
      (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics
      of academic domains from students' perspective. In Study 2 (N = 1709; 8th and
      11th graders) the 13 characteristics identified in Study 1 were assessed along
      with academic emotions in four different domains (mathematics, physics, German,
      and English) using a questionnaire-based trait assessment. With respect to the
      same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th
      graders) by employing an experience sampling approach. In line with our initial
      assumptions, between-domain relations of trait but not state academic emotions
      reflected between-domain relations of domain characteristics. Implications for
      research and practice are discussed. 

PMID- 25374550
TI  - The great outdoors? Exploring the mental health benefits of natural environments.

PMID- 25374549
TI  - TVA-based assessment of attentional capacities-associations with age and indices
      of brain white matter microstructure.
AB  - In this study the primary aims were to characterize the effects of age on basic
      components of visual attention derived from assessments based on a theory of
      visual attention (TVA) in 325 healthy volunteers covering the adult lifespan (19
      81 years). Furthermore, we aimed to investigate how age-related differences on
      TVA parameters are associated with white matter (WM) microstructure as indexed by
      diffusion tensor imaging (DTI). Finally, we explored how TVA parameter estimates
      were associated with complex, or multicomponent indices of processing speed
      (Digit-symbol substitution, DSS) and fluid intelligence (gF). The results
      indicated that the TVA parameters for visual short-term memory capacity, K, and
      for attentional selectivity, alpha, were most strongly associated with age before
      the age of 50. However, in this age range, it was the parameter for processing
      speed, C, that was most clearly associated with DTI indices, in this case
      fractional anisotropy (FA), particularly in the genu and body of the corpus
      callosum. Furthermore, differences in the C parameter partially mediated
      differences in DSS within this age range. After the age of 50, the TVA parameter
      for the perceptual threshold, t 0, as well as K, were most strongly related to
      participant age. Both parameters, but t 0 more strongly so than K, were
      associated WM diffusivity, particularly in projection fibers such as the internal
      capsule, the sagittal stratum, and the corona radiata. Within this age range, t 0
      partially mediated age-related differences in gF. The results are consistent
      with, and provide novel empirical support for the neuroanatomical localization of
      TVA computations as outlined in the neuronal interpretation of TVA (NTVA).
      Furthermore, the results indicate that to understand the biological sources of
      age-related changes in processing speed and fluid cognition, it may be useful to
      employ methods that allow for computational fractionation of these multicomponent
      measures. 

PMID- 25374551
TI  - Bilingualism affects audiovisual phoneme identification.
AB  - We all go through a process of perceptual narrowing for phoneme identification.
      As we become experts in the languages we hear in our environment we lose the
      ability to identify phonemes that do not exist in our native phonological
      inventory. This research examined how linguistic experience-i.e., the exposure to
      a double phonological code during childhood-affects the visual processes involved
      in non-native phoneme identification in audiovisual speech perception. We
      conducted a phoneme identification experiment with bilingual and monolingual
      adult participants. It was an ABX task involving a Bengali dental-retroflex
      contrast that does not exist in any of the participants' languages. The phonemes
      were presented in audiovisual (AV) and audio-only (A) conditions. The results
      revealed that in the audio-only condition monolinguals and bilinguals had
      difficulties in discriminating the retroflex non-native phoneme. They were
      phonologically "deaf" and assimilated it to the dental phoneme that exists in
      their native languages. In the audiovisual presentation instead, both groups
      could overcome the phonological deafness for the retroflex non-native phoneme and
      identify both Bengali phonemes. However, monolinguals were more accurate and
      responded quicker than bilinguals. This suggests that bilinguals do not use the
      same processes as monolinguals to decode visual speech. 

PMID- 25374548
TI  - Probing feedforward and feedback contributions to awareness with visual masking
      and transcranial magnetic stimulation.
AB  - A number of influential theories posit that visual awareness relies not only on
      the initial, stimulus-driven (i.e., feedforward) sweep of activation but also on
      recurrent feedback activity within and between brain regions. These theories of
      awareness draw heavily on data from masking paradigms in which visibility of one
      stimulus is reduced due to the presence of another stimulus. More recently
      transcranial magnetic stimulation (TMS) has been used to study the temporal
      dynamics of visual awareness. TMS over occipital cortex affects performance on
      visual tasks at distinct time points and in a manner that is comparable to visual
      masking. We draw parallels between these two methods and examine evidence for the
      neural mechanisms by which visual masking and TMS suppress stimulus visibility.
      Specifically, both methods have been proposed to affect feedforward as well as
      feedback signals when applied at distinct time windows relative to stimulus onset
      and as a result modify visual awareness. Most recent empirical evidence,
      moreover, suggests that while visual masking and TMS impact stimulus visibility
      comparably, the processes these methods affect may not be as similar as
      previously thought. In addition to reviewing both masking and TMS studies that
      examine feedforward and feedback processes in vision, we raise questions to guide
      future studies and further probe the necessary conditions for visual awareness. 

PMID- 25374552
TI  - Photographs of manipulable objects are named more quickly than the same objects
      depicted as line-drawings: Evidence that photographs engage embodiment more than
      line-drawings.
AB  - Previous research has shown that photographs of manipulable objects (i.e., those
      that can be grasped for use with one hand) are named more quickly than non
      manipulable objects when they have been matched for object familiarity and age of
      acquisition. The current study tested the hypothesis that the amount of visual
      detail present in object depictions moderates these "manipulability" effects on
      object naming. The same objects were presented as photographs and line-drawings
      during a speeded naming task. Forty-six participants named 222 objects depicted
      in both formats. A significant object depiction (photographs versus line drawing)
      by manipulability interaction confirmed our hypothesis that manipulable objects
      are identified more quickly when shown as photographs; whereas, non-manipulable
      objects are identified equally quickly when shown as photographs versus line
      drawings. These results indicate that factors such as surface detail and texture
      moderate the role of "action" and/or "manipulability" effects during object
      identification tasks, and suggest that photographs of manipulable objects are
      associated with more embodied representations of those objects than when they are
      depicted as line-drawings. 

PMID- 25374553
TI  - Understanding Group and Leader (UGL) trainers' personality characteristics and
      affective profiles.
AB  - BACKGROUND: The Understanding Group and Leader (UGL), provided by the Swedish
      National Defense College and mentored by UGL-trainers, is one of the most popular
      management programs among civilians in Sweden. However, there is a lack of
      scientific evidence regarding the training. We used the affective profile model
      (i.e., the combination of positive, PA, and negative affect, NA) to mapp
      important markers of empowerment, self-awareness, adaptive coping skills, and
      maturity among the UGL-trainers. The aims were: (1) to compare profiles between
      UGL-trainers and managers/supervisors and (2) to investigate differences in
      personal characteristics. METHOD: UGL-trainers (N = 153) and the comparison group
      (104 Swedish Chiefs of Police) completed an online survey on optimism, self
      esteem, locus of control, and affect. The four profiles are: self-fulfilling
      (high PA, low NA), high affective (high PA, high NA), low affective (high PA, low
      NA), and self-destructive (low PA, high NA). RESULTS: The self-fulfilling profile
      was more common among UGL-trainers (25.70%) than among Chiefs of Police (19.20%).
      UGL-trainers, compared to Chiefs of Police, were more likely to express a self
      fulling than a low affective profile (OR = 2.22, p < 0.05) and a high affective
      than a low affective profile (OR = 1.43, p < 0.001). UGL-trainers with a self
      fulfilling profile, compared to those with a self-destructive profile, scored
      higher in optimism, higher in self-esteem, and lower in external locus of
      control. CONCLUSIONS: The probability of self-fulfillment rather than low
      affectivity was higher among UGL-trainers. Self-fulfillment was associated to
      markers of self-awareness and adaptive coping skills. However, the most common
      profile was the low affective, which is associated to low performance during
      stress, low degree of personal development, low degree of purpose in life, and
      low resilience. Hence, it might be important for UGL-trainers to have a
      continuous training in awareness after certification.

PMID- 25374555
TI  - Culture, neuroscience, and law.

PMID- 25374554
TI  - Visual crowding illustrates the inadequacy of local vs. global and feedforward
      vs. feedback distinctions in modeling visual perception.
AB  - Experimentalists tend to classify models of visual perception as being either
      local or global, and involving either feedforward or feedback processing. We
      argue that these distinctions are not as helpful as they might appear, and we
      illustrate these issues by analyzing models of visual crowding as an example.
      Recent studies have argued that crowding cannot be explained by purely local
      processing, but that instead, global factors such as perceptual grouping are
      crucial. Theories of perceptual grouping, in turn, often invoke feedback
      connections as a way to account for their global properties. We examined three
      types of crowding models that are representative of global processing models, and
      two of which employ feedback processing: a model based on Fourier filtering, a
      feedback neural network, and a specific feedback neural architecture that
      explicitly models perceptual grouping. Simulations demonstrate that crucial
      empirical findings are not accounted for by any of the models. We conclude that
      empirical investigations that reject a local or feedforward architecture offer
      almost no constraints for model construction, as there are an uncountable number
      of global and feedback systems. We propose that the identification of a system as
      being local or global and feedforward or feedback is less important than the
      identification of a system's computational details. Only the latter information
      can provide constraints on model development and promote quantitative
      explanations of complex phenomena. 

PMID- 25374556
TI  - Enhancing semantic congruity effects with category-contingent comparative
      judgments.
AB  - In each of two experiments the direction of a binary comparison was contingent on
      the category of the stimulus pair. In one experiment, participants had to compare
      the size of animals from memory. On congruent trials, they had to select the
      smaller animal if both were small and the larger if both were large and on
      incongruent trials they selected the larger if both were small and the smaller if
      both were large. In a second experiment, participants had to compare visual
      extents and the direction of the comparison was contingent on whether the lines
      were short or long. Response times were increased and semantic congruity effects
      (SCEs) were greatly amplified with the category-contingent instructions relative
      to the conventional non-contingent instructions, precisely as predicted by the
      class of evidence accrual models of decisional processing and contrary to the
      single-sample stage models of the SCE. 

PMID- 25374557
TI  - The perception of the French /s/-/?/ contrast in early Creole-French bilinguals.
AB  - One particularity of the Mauritian Creole language is that there is no
      contrastive distinction between the consonants /s/ and /?/, which are both
      pronounced /s/ in Creole. In this study, we examined the identification
      performance of the /s/-/?/ contrast by Mauritian Creole-French bilinguals who
      have been exposed to French before 7 years of age, and who have been raised in a
      highly Creole-French bilingual society. The results showed that most of our
      bilingual participants identify the /s/ and /?/ consonants like native French
      speakers. It also appeared that the way in which the two consonants are
      categorized can be manipulated by introducing subtle changes in the information
      these participants were given about the identity of the speaker that produced the
      stimuli. Our results are in accordance with recent studies showing native-like
      performance in bilinguals on a categorization task and, importantly, extend these
      findings to speakers of a Creole language. In addition, these results show that
      speech sound categorization can be influenced by information about the speaker's
      social identity and thus argue for models that postulate rich speech sound
      representations. 

PMID- 25374558
TI  - What "causal cognition" might mean.

PMID- 25374559
TI  - A novel mouse model of penetrating brain injury.
AB  - Penetrating traumatic brain injury (pTBI) has been difficult to model in small
      laboratory animals, such as rats or mice. Previously, we have established a non
      fatal, rat model for pTBI using a modified air-rifle that accelerates a pellet,
      which hits a small probe that then penetrates the experimental animal's brain.
      Knockout and transgenic strains of mice offer attractive tools to study
      biological reactions induced by TBI. Hence, in the present study, we adapted and
      modified our model to be used with mice. The technical characterization of the
      impact device included depth and speed of impact, as well as dimensions of the
      temporary cavity formed in a brain surrogate material after impact. Biologically,
      we have focused on three distinct levels of severity (mild, moderate, and
      severe), and characterized the acute phase response to injury in terms of tissue
      destruction, neural degeneration, and gliosis. Functional outcome was assessed by
      measuring bodyweight and motor performance on rotarod. The results showed that
      this model is capable of reproducing major morphological and neurological changes
      of pTBI; as such, we recommend its utilization in research studies aiming to
      unravel the biological events underlying injury and regeneration after pTBI. 

PMID- 25374560
TI  - Testis cancer: genes, environment, hormones.

PMID- 25374561
TI  - New insights on the Intrinsic, Pro-Apoptotic Effect of IGFB3 in Breast Cancer.

PMID- 25374562
TI  - The role of dendritic cells in immunity against primary herpes simplex virus
      infections.
AB  - Herpes simplex virus (HSV) is a DNA virus with tropism for infecting skin and
      mucosal epithelia during the lytic stages of its complex life cycle. The immune
      system has evolved a multitude of strategies to respond to primary HSV
      infections. These include rapid innate immune responses largely driven by pattern
      recognition systems and protective anti-viral immunity. Dendritic cells (DC)
      represent a versatile and heterogenic group of antigen presenting cells that are
      important for pathogen recognition at sites of infection and for priming of
      protective HSV-specific T cells. Here we will review the current knowledge on the
      role of DCs in the host immune response to primary HSV infection. We will discuss
      how DCs integrate viral cues into effective innate immune responses, will dissect
      how HSV infection of DCs interferes with their capacity to migrate from sites of
      infection to the draining lymph nodes and will outline how migratory DCs can make
      antigens available to lymph node resident DCs. The role of distinct DC subsets
      and their relevant contribution to antigen presentation on MHC class I and MHC
      class II molecules will be detailed in the context of T cell priming in the lymph
      node and the elicitation of effector function in infected tissues. An improved
      understanding of the fundamental mechanisms of how DCs recognize HSV, process and
      present its antigens to naive and effector T cells will not only assist in the
      improvement of vaccine-based preventions of this important viral disease, but
      also serves as a paradigm to resolve basic immunological principles. 

PMID- 25374563
TI  - Protein-tyrosine phosphorylation interaction network in Bacillus subtilis reveals
      new substrates, kinase activators and kinase cross-talk.
AB  - Signal transduction in eukaryotes is generally transmitted through
      phosphorylation cascades that involve a complex interplay of transmembrane
      receptors, protein kinases, phosphatases and their targets. Our previous work
      indicated that bacterial protein-tyrosine kinases and phosphatases may exhibit
      similar properties, since they act on many different substrates. To capture the
      complexity of this phosphorylation-based network, we performed a comprehensive
      interactome study focused on the protein-tyrosine kinases and phosphatases in the
      model bacterium Bacillus subtilis. The resulting network identified many
      potential new substrates of kinases and phosphatases, some of which were
      experimentally validated. Our study highlighted the role of tyrosine and
      serine/threonine kinases and phosphatases in DNA metabolism, transcriptional
      control and cell division. This interaction network reveals significant crosstalk
      among different classes of kinases. We found that tyrosine kinases can bind to
      several modulators, transmembrane or cytosolic, consistent with a branching of
      signaling pathways. Most particularly, we found that the division site regulator
      MinD can form a complex with the tyrosine kinase PtkA and modulate its activity
      in vitro. In vivo, it acts as a scaffold protein which anchors the kinase at the
      cell pole. This network highlighted a role of tyrosine phosphorylation in the
      spatial regulation of the Z-ring during cytokinesis. 

PMID- 25374565
TI  - Activity and abundance of methane-oxidizing bacteria in secondary forest and
      manioc plantations of Amazonian Dark Earth and their adjacent soils.
AB  - The oxidation of atmospheric CH4 in upland soils is mostly mediated by
      uncultivated groups of microorganisms that have been identified solely by
      molecular markers, such as the sequence of the pmoA gene encoding the beta
      subunit of the particulate methane monooxygenase enzyme. The objective of this
      work was to compare the activity and diversity of methanotrophs in Amazonian Dark
      Earth soil (ADE, Hortic Anthrosol) and their adjacent non-anthropic soil.
      Secondly, the effect of land use in the form of manioc cultivation was examined
      by comparing secondary forest and plantation soils. CH4 oxidation potentials were
      measured and the structure of the methanotroph communities assessed by
      quantitative PCR (qPCR) and amplicon pyrosequencing of pmoA genes. The oxidation
      potentials at low CH4 concentrations (10 ppm of volume) were relatively high in
      all the secondary forest sites of both ADE and adjacent soils. CH4 oxidation by
      the ADE soil only recently converted to a manioc plantation was also relatively
      high. In contrast, both the adjacent soils used for manioc cultivation and the
      ADE soil with a long history of agriculture displayed lower CH4 uptake rates.
      Amplicon pyrosequencing of pmoA genes indicated that USCalpha, Methylocystis and
      the tropical upland soil cluster (TUSC) were the dominant groups depending on the
      site. By qPCR analysis it was found that USCalpha pmoA genes, which are believed
      to belong to atmospheric CH4 oxidizers, were more abundant in ADE than adjacent
      soil. USCalpha pmoA genes were abundant in both forested and cultivated ADE soil,
      but were below the qPCR detection limit in manioc plantations of adjacent soil.
      The results indicate that ADE soils can harbor high abundances of atmospheric CH4
      oxidizers and are potential CH4 sinks, but as in other upland soils this activity
      can be inhibited by the conversion of forest to agricultural plantations. 

PMID- 25374566
TI  - Pathophysiology and epidemiology of virus-induced asthma.

PMID- 25374564
TI  - Regulatory role of tetR gene in a novel gene cluster of Acidovorax avenae subsp.
      avenae RS-1 under oxidative stress.
AB  - Acidovorax avenae subsp. avenae is the causal agent of bacterial brown stripe
      disease in rice. In this study, we characterized a novel horizontal transfer of a
      gene cluster, including tetR, on the chromosome of A. avenae subsp. avenae RS-1
      by genome-wide analysis. TetR acted as a repressor in this gene cluster and the
      oxidative stress resistance was enhanced in tetR-deletion mutant strain.
      Electrophoretic mobility shift assay demonstrated that TetR regulator bound
      directly to the promoter of this gene cluster. Consistently, the results of
      quantitative real-time PCR also showed alterations in expression of associated
      genes. Moreover, the proteins affected by TetR under oxidative stress were
      revealed by comparing proteomic profiles of wild-type and mutant strains via 1D
      SDS-PAGE and LC-MS/MS analyses. Taken together, our results demonstrated that
      tetR gene in this novel gene cluster contributed to cell survival under oxidative
      stress, and TetR protein played an important regulatory role in growth kinetics,
      biofilm-forming capability, superoxide dismutase and catalase activity, and oxide
      detoxicating ability. 

PMID- 25374567
TI  - Vascular endothelium as a target of immune response in renal transplant
      rejection.
AB  - This review of clinical and experimental studies aims at analyzing the interplay
      between graft endothelium and host immune system in renal transplantation, and
      how it affects the survival of the graft. Graft endothelium is indeed the first
      barrier between self and non-self that is encountered by host lymphocytes upon
      reperfusion of vascularized solid transplants. Endothelial cells (EC) express all
      the major sets of antigens (Ag) that elicit host immune response, and therefore
      represent a preferential target in organ rejection. Some of the Ag expressed by
      EC are target of the antibody-mediated response, such as the AB0 blood group
      system, the human leukocyte antigens (HLA), and MHC class I related chain A
      antigens (MICA) systems, and the endothelial cell-restricted Ag; for each of
      these systems, the mechanisms of interaction and damage of both preformed and de
      novo donor-specific antibodies are reviewed along with their impact on renal
      graft survival. Moreover, the rejection process can force injured EC to expose
      cryptic self-Ag, toward which an autoimmune response mounts, overlapping to the
      allo-immune response in the damaging of the graft. Not only are EC a passive
      target of the host immune response but also an active player in lymphocyte
      activation; therefore, their interaction with allogenic T-cells is analyzed on
      the basis of experimental in vitro and in vivo studies, according to the patterns
      of expression of the HLA class I and II and the co-stimulatory molecules specific
      for cytotoxic and helper T-cells. Finally, as the response that follows
      transplantation has proven to be not necessarily destructive, the factors that
      foster graft endothelium functioning in spite of rejection, and how they could be
      therapeutically harnessed to promote long-term graft acceptance, are described:
      accommodation that is resistance of EC to donor-specific antibodies, and
      endothelial cell ability to induce Foxp3+ regulatory T-cells, that are crucial
      mediators of tolerance. 

PMID- 25374568
TI  - Neutrophil-derived cytokines: facts beyond expression.
AB  - Polymorphonuclear neutrophils, besides their involvement in primary defense
      against infections - mainly through phagocytosis, generation of toxic molecules,
      release of enzymes, and formation of extracellular traps - are also becoming
      increasingly important for their contribution to the fine regulation in
      development of inflammatory and immune responses. These latter functions of
      neutrophils occur, in part, via their de novo production and release of a large
      variety of cytokines, including chemotactic cytokines (chemokines). Accordingly,
      the improvement in technologies for molecular and functional cell analysis, along
      with concomitant advances in cell purification techniques, have allowed the
      identification of a continuously growing list of neutrophil-derived cytokines, as
      well as the characterization of their biological implications in vitro and/or in
      vivo. This short review summarizes crucial concepts regarding the modalities of
      expression, release, and regulation of neutrophil-derived cytokines. It also
      highlights examples illustrating the potential implications of neutrophil-derived
      cytokines according to recent observations made in humans and/or in experimental
      animal models. 

PMID- 25374569
TI  - Potential Use of gammadelta T Cell-Based Vaccines in Cancer Immunotherapy.
AB  - IMMUNOTHERAPY IS A FAST ADVANCING METHODOLOGY INVOLVING ONE OF TWO APPROACHES:
      (1) compounds targeting immune checkpoints and (2) cellular immunomodulators. The
      latter approach is still largely experimental and features in vitro generated,
      live immune effector cells, or antigen-presenting cells. gammadelta T cells are
      known for their efficient in vitro tumor killing activities. Consequently, many
      laboratories worldwide are currently testing the tumor killing function of
      gammadelta T cells in clinical trials. Reported benefits are modest; however,
      these studies have demonstrated that large gammadelta T-cell infusions were well
      tolerated. Here, we discuss the potential of using human gammadelta T cells not
      as effector cells but as a novel cellular vaccine for treatment of cancer
      patients. Antigen-presenting gammadelta T cells do not require to home to tumor
      tissues but, instead, need to interact with endogenous, tumor-specific alphabeta
      T cells in secondary lymphoid tissues. Newly mobilized effector alphabeta T cells
      are then thought to overcome the immune blockade by creating proinflammatory
      conditions fit for effector T-cell homing to and killing of tumor cells.
      Immunotherapy may include tumor antigen-loaded gammadelta T cells alone or in
      combination with immune checkpoint inhibitors. 

PMID- 25374572
TI  - Update on controls for isolation and quantification methodology of extracellular
      vesicles derived from adipose tissue mesenchymal stem cells.
AB  - The research field on extracellular vesicles (EV) has rapidly expanded in recent
      years due to the therapeutic potential of EV. Adipose tissue human mesenchymal
      stem cells (ASC) may be a suitable source for therapeutic EV. A major limitation
      in the field is the lack of standardization of the challenging techniques to
      isolate and characterize EV. The aim of our study was to incorporate new controls
      for the detection and quantification of EV derived from ASC and to analyze the
      applicability and limitations of the available techniques. ASC were cultured in
      medium supplemented with 5% of vesicles-free fetal bovine serum. The EV were
      isolated from conditioned medium by differential centrifugation with size
      filtration (0.2 MUm). As a control, non-conditioned culture medium was used
      (control medium). To detect EV, electron microscopy, conventional flow cytometry,
      and western blot were used. The quantification of the EV was by total protein
      quantification, ExoELISA immunoassay, and Nanosight. Cytokines and growth factors
      in the EV samples were measured by multiplex bead array kit. The EV were detected
      by electron microscope. Total protein measurement was not useful to quantify EV
      as the control medium showed similar protein contents as the EV samples. The
      ExoELISA kits had technical troubles and it was not possible to quantify the
      concentration of exosomes in the samples. The use of Nanosight enabled
      quantification and size determination of the EV. It is, however, not possible to
      distinguish protein aggregates from EV with this method. The technologies for
      quantification and characterization of the EV need to be improved. In addition,
      we detected protein contaminants in the EV samples, which make it difficult to
      determine the real effect of EV in experimental models. It will be crucial in the
      future to optimize design novel methods for purification and characterization of
      EV. 

PMID- 25374571
TI  - Evidence That Erythropoietin Modulates Neuroinflammation through Differential
      Action on Neurons, Astrocytes, and Microglia.
AB  - Neuroinflammation is a normal and healthy response to neuronal damage. However,
      excessive or chronic neuroinflammation exacerbates neurodegeneration after trauma
      and in progressive diseases such as Alzheimer's, Parkinson's, age-related macular
      degeneration, and glaucoma. Therefore, molecules that modulate neuroinflammation
      are candidates as neuroprotective agents. Erythropoietin (EPO) is a known
      neuroprotective agent that indirectly attenuates neuroinflammation, in part, by
      inhibiting neuronal apoptosis. In this review, we provide evidence that EPO also
      modulates neuroinflammation upstream of apoptosis by acting directly on glia.
      Further, the signaling induced by EPO may differ depending on cell type and
      context possibly as a result of activation of different receptors. While
      significant progress has been made in our understanding of EPO signaling, this
      review also identifies areas for future study in terms of the role of EPO in
      modulating neuroinflammation. 

PMID- 25374570
TI  - Immunotherapeutic potential of extracellular vesicles.
AB  - Extracellular vesicle or EV is a term that encompasses all classes of secreted
      lipid membrane vesicles. Despite being scientific novelties, EVs are gaining
      importance as a mediator of important physiological and pathological
      intercellular activities possibly through the transfer of their cargo of protein
      and RNA between cells. In particular, exosomes, the currently best characterized
      EVs have been notable for their in vitro and in vivo immunomodulatory activities.
      Exosomes are nanometer-sized endosome-derived vesicles secreted by many cell
      types and their immunomodulatory potential is independent of their cell source.
      Besides immune cells such as dendritic cells, macrophages, and T cells, cancer
      and stem cells also secrete immunologically active exosomes that could influence
      both physiological and pathological processes. The immunological activities of
      exosomes affect both innate and adaptive immunity and include antigen
      presentation, T cell activation, T cell polarization to regulatory T cells,
      immune suppression, and anti-inflammation. As such, exosomes carry much
      immunotherapeutic potential as a therapeutic agent and a therapeutic target. 

PMID- 25374573
TI  - A chromatin modifying enzyme, SDG8, is involved in morphological, gene
      expression, and epigenetic responses to mechanical stimulation.
AB  - Thigmomorphogenesis is viewed as being a response process of acclimation to short
      repetitive bursts of mechanical stimulation or touch. The underlying molecular
      mechanisms that coordinate changes in how touch signals lead to long-term
      morphological changes are enigmatic. Touch responsive gene expression is rapid
      and transient, and no transcription factor or DNA regulatory motif has been
      reported that could confer a genome wide mechanical stimulus. We report here on a
      chromatin modifying enzyme, SDG8/ASHH2, which can regulate the expression of many
      touch responsive genes identified in Arabidopsis. SDG8 is required for the
      permissive expression of touch induced genes; and the loss of function of sdg8
      perturbs the maximum levels of induction on selected touch gene targets. SDG8 is
      required to maintain permissive H3K4 trimethylation marks surrounding the
      Arabidopsis touch-inducible gene TOUCH 3 (TCH3), which encodes a calmodulin-like
      protein (CML12). The gene neighboring was also slightly down regulated, revealing
      a new target for SDG8 mediated chromatin modification. Finally, sdg8 mutants show
      perturbed morphological response to wind-agitated mechanical stimuli, implicating
      an epigenetic memory-forming process in the acclimation response of
      thigmomorphogenesis. 

PMID- 25374574
TI  - Overexpression of patatin-related phospholipase AIIIbeta altered the content and
      composition of sphingolipids in Arabidopsis.
AB  - In plants, fatty acids are primarily synthesized in plastids and then transported
      to the endoplasmic reticulum (ER) for synthesis of most of the complex membrane
      lipids, including glycerolipids and sphingolipids. The first step of sphingolipid
      synthesis, which uses a fatty acid and a serine as substrates, is critical for
      sphingolipid homeostasis; its disruption leads to an altered plant growth.
      Phospholipase As have been implicated in the trafficking of fatty acids from
      plastids to the ER. Previously, we found that overexpression of a patatin-related
      phospholipase, pPLAIIIbeta, resulted in a smaller plant size and altered
      anisotropic cell expansion. Here, we determined the content and composition of
      sphingolipids in pPLAIIIbeta-knockout and overexpression plants (pPLAIIIbeta-KO
      and -OE). 3-keto-sphinganine, the product of the first step of sphingolipid
      synthesis, had a 26% decrease in leaves of pPLAIIIbeta-KO while a 52% increase in
      pPLAIIIbeta-OE compared to wild type (WT). The levels of free long-chain base
      species, dihydroxy-C18:0 and trihydroxy-18:0 (d18:0 and t18:0), were 38 and 97%
      higher, respectively, in pPLAIIIbeta-OE than in WT. The level of complex
      sphingolipids ceramide d18:0-16:0 and t18:1-16:0 had a twofold increase in
      pPLAIIIbeta-OE. The level of hydroxy ceramide d18:0-h16:0 was 72% higher in
      pPLAIIIbeta-OE compared to WT. The levels of several species of glucosylceramide
      and glycosylinositolphosphoceramide tended to be higher in pPLAIIIbeta-OE than in
      WT. The total content of the complex sphingolipids showed a slightly higher in
      pPLAIIIbeta-OE than in WT. These results revealed an involvement of phospholipase
      mediated lipid homeostasis in plant growth. 

PMID- 25374576
TI  - Stochastic models of cellular circadian rhythms in plants help to understand the
      impact of noise on robustness and clock structure.
AB  - Rhythmic behavior is essential for plants; for example, daily (circadian) rhythms
      control photosynthesis and seasonal rhythms regulate their life cycle. The core
      of the circadian clock is a genetic network that coordinates the expression of
      specific clock genes in a circadian rhythm reflecting the 24-h day/night cycle.
      Circadian clocks exhibit stochastic noise due to the low copy numbers of clock
      genes and the consequent cell-to-cell variation: this intrinsic noise plays a
      major role in circadian clocks by inducing more robust oscillatory behavior.
      Another source of noise is the environment, which causes variation in temperature
      and light intensity: this extrinsic noise is part of the requirement for the
      structural complexity of clock networks. Advances in experimental techniques now
      permit single-cell measurements and the development of single-cell models. Here
      we present some modeling studies showing the importance of considering both types
      of noise in understanding how plants adapt to regular and irregular light
      variations. Stochastic models have proven useful for understanding the effect of
      regular variations. By contrast, the impact of irregular variations and the
      interaction of different noise sources are less well studied. 

PMID- 25374575
TI  - Mechanosensitive channels: feeling tension in a world under pressure.
AB  - Plants, like other organisms, are facing multiple mechanical constraints
      generated both in their tissues and by the surrounding environments. They need to
      sense and adapt to these forces throughout their lifetimes. To do so, different
      mechanisms devoted to force transduction have emerged. Here we focus on
      fascinating proteins: the mechanosensitive (MS) channels. Mechanosensing in
      plants has been described for centuries but the molecular identification of MS
      channels occurred only recently. This review is aimed at plant biologists and
      plant biomechanists who want to be introduced to MS channel identity, how they
      work and what they might do in planta? In this review, electrophysiological
      properties, regulations, and functions of well-characterized MS channels
      belonging to bacteria and animals are compared with those of plants. Common and
      specific properties are discussed. We deduce which tools and concepts from animal
      and bacterial fields could be helpful for improving our understanding of plant
      mechanotransduction. MS channels embedded in their plasma membrane are sandwiched
      between the cell wall and the cytoskeleton. The consequences of this peculiar
      situation are analyzed and discussed. We also stress how important it is to probe
      mechanical forces at cellular and subcellular levels in planta in order to reveal
      the intimate relationship linking the membrane with MS channel activity. Finally
      we will propose new tracks to help to reveal their physiological functions at
      tissue and plant levels. 

PMID- 25374577
TI  - Leaf silica concentration in Serengeti grasses increases with watering but not
      clipping: insights from a common garden study and literature review.
AB  - Grasses (Poaceae) lack the complex biochemical pathways and structural defenses
      employed by other plant families; instead they deposit microscopic silica (SiO2)
      granules in their leaf blades (i.e., phytoliths) as a putative defense strategy.
      Silica accumulation in grasses has generally been considered an inducible
      defense; other research suggests silica accumulation occurs by passive diffusion
      and should therefore be closely coupled with whole plant transpiration. We tested
      the hypothesis that grasses increase leaf silica concentration in response to
      artificial defoliation in a common garden study in the Serengeti ecosystem of
      East Africa. Additionally, a watering treatment tested the alternative hypothesis
      that leaf silica was largely driven by plant water status. Leaf silica content of
      two dominant C4 Serengeti grass species, Themeda triandra and Digitaria
      macroblephara, was quantified after a 10-month clipping * water experiment in
      which defoliation occurred approximately every 2 months and supplementary water
      was added every 2 weeks. Themeda had greater silica content than Digitaria, and
      Themeda also varied in foliar silica content according to collection site.
      Clipping had no significant effect on leaf silica in either species and watering
      significantly increased silica content of the dominant tall grass species,
      Themeda, but not the lawn species, Digitaria. Our data, and those collected as
      part of a supplementary literature review, suggest that silicon induction
      responses are contingent upon a combination of plant identity (i.e., species,
      genotype, life history limitations) and environmental factors (i.e.,
      precipitation, soil nutrients, grazing intensity). Specifically, we propose that
      an interaction between plant functional type and water balance plays an
      especially important role in determining silica uptake and accumulation. 

PMID- 25374578
TI  - The role of silicon in plant tissue culture.
AB  - Growth and morphogenesis of in vitro cultures of plant cells, tissues, and organs
      are greatly influenced by the composition of the culture medium. Mineral
      nutrients are necessary for the growth and development of plants. Several morpho
      physiological disorders such as hooked leaves, hyperhydricity, fasciation, and
      shoot tip necrosis are often associated with the concentration of inorganic
      nutrient in the tissue culture medium. Silicon (Si) is the most abundant mineral
      element in the soil. The application of Si has been demonstrated to be beneficial
      for growth, development and yield of various plants and to alleviate various
      stresses including nutrient imbalance. Addition of Si to the tissue culture
      medium improves organogenesis, embryogenesis, growth traits, morphological,
      anatomical, and physiological characteristics of leaves, enhances tolerance to
      low temperature and salinity, protects cells and against metal toxicity, prevents
      oxidative phenolic browning and reduces the incidence of hyperhydricity in
      various plants. Therefore, Si possesses considerable potential for application in
      a wide range of plant tissue culture studies such as cryopreservation,
      organogenesis, micropropagation, somatic embryogenesis and secondary metabolites
      production. 

PMID- 25374579
TI  - To control and to be controlled: understanding the Arabidopsis SLIM1 function in
      sulfur deficiency through comprehensive investigation of the EIL protein family.
AB  - Sulfur limitation 1 (SLIM1), a member of the EIN3-like (EIL) family of
      transcription factors in Arabidopsis, is the regulator of many sulfur deficiency
      responsive genes. Among the five other proteins of the family, three regulate
      ethylene (ET) responses and two have unassigned functions. Contrary to the well
      defined ET signaling, the pathway leading from sensing sulfate status to the
      activation of its acquisition via SLIM1 is completely unknown. SLIM1 binds to the
      20 nt-long specific UPE-box sequence; however, it also recognizes the shorter
      TEIL sequence, unique for the whole EIL family. SLIM1 takes part in the
      upregulation and downregulation of various sulfur metabolism genes, but also it
      controls the degradation of glucosinolates under sulfur deficient conditions.
      Besides facilitating the increased flux through the sulfate assimilation pathway,
      SLIM1 induces microRNA395, specifically targeting ATP sulfurylases and a low
      affinity sulfate transporter, SULTR2;1, thus affecting sulfate translocation to
      the shoot. Here, we briefly review the identification, structural
      characteristics, and molecular function of SLIM1 from the perspective of the
      whole EIL protein family. 

PMID- 25374580
TI  - Methylated DNA is over-represented in whole-genome bisulfite sequencing data.
AB  - The development of whole-genome bisulfite sequencing (WGBS) has resulted in a
      number of exciting discoveries about the role of DNA methylation leading to a
      plethora of novel testable hypotheses. Methods for constructing sodium bisulfite
      converted and amplified libraries have recently advanced to the point that the
      bottleneck for experiments that use WGBS has shifted to data analysis and
      interpretation. Here we present empirical evidence for an over-representation of
      reads from methylated DNA in WGBS. This enrichment for methylated DNA is
      exacerbated by higher cycles of PCR and is influenced by the type of uracil
      insensitive DNA polymerase used for amplifying the sequencing library. Future
      efforts to computationally correct for this enrichment bias will be essential to
      increasing the accuracy of determining methylation levels for individual
      cytosines. It is especially critical for studies that seek to accurately quantify
      DNA methylation levels in populations that may segregate for allelic DNA
      methylation states. 

PMID- 25374581
TI  - Revisiting the vanishing refuge model of diversification.
AB  - Much of the debate around speciation and historical biogeography has focused on
      the role of stabilizing selection on the physiological (abiotic) niche,
      emphasizing how isolation and vicariance, when associated with niche
      conservatism, may drive tropical speciation. Yet, recent re-emphasis on the
      ecological dimensions of speciation points to a more prominent role of divergent
      selection in driving genetic, phenotypic, and niche divergence. The vanishing
      refuge model (VRM), first described by Vanzolini and Williams (1981), describes a
      process of diversification through climate-driven habitat fragmentation and
      exposure to new environments, integrating both vicariance and divergent
      selection. This model suggests that dynamic climates and peripheral isolates can
      lead to genetic and functional (i.e., ecological and phenotypic) diversity,
      resulting in sister taxa that occupy contrasting habitats with abutting
      distributions. Here, we provide predictions for populations undergoing divergence
      according to the VRM that encompass habitat dynamics, phylogeography, and
      phenotypic differentiation across populations. Such integrative analyses can, in
      principle, differentiate the operation of the VRM from other speciation models.
      We applied these principles to a lizard species, Coleodactylus meridionalis,
      which was used to illustrate the model in the original paper. We incorporate data
      on inferred historic habitat dynamics, phylogeography and thermal physiology to
      test for divergence between coastal and inland populations in the Atlantic Forest
      of Brazil. Environmental and genetic analyses are concordant with divergence
      through the VRM, yet physiological data are not. We emphasize the importance of
      multidisciplinary approaches to test this and alternative speciation models while
      seeking to explain the extraordinarily high genetic and phenotypic diversity of
      tropical biomes. 

PMID- 25374582
TI  - Genetic selection for temperament traits in dairy and beef cattle.
AB  - Animal temperament can be defined as a response to environmental or social
      stimuli. There are a number of temperament traits in cattle that contribute to
      their welfare, including their response to handling or milking, response to
      challenge such as human approach or intervention at calving, and response to
      conspecifics. In a number of these areas, the genetic basis of the trait has been
      studied. Heritabilities have been estimated and in some cases quantitative trait
      loci (QTL) have been identified. The variation is sometimes considerable and
      moderate heritabilities have been found for the major handling temperament
      traits, making them amenable to selection. Studies have also investigated the
      correlations between temperament and other traits, such as productivity and meat
      quality. Despite this, there are relatively few examples of temperament traits
      being used in selection programmes. Most often, animals are screened for
      aggression or excessive fear during handling or milking, with extreme animals
      being culled, or EBVs for temperament are estimated, but these traits are not
      commonly included routinely in selection indices, despite there being economic,
      welfare and human safety drivers for their. There may be a number of constraints
      and barriers. For some traits and breeds, there may be difficulties in collecting
      behavioral data on sufficiently large populations of animals to estimate genetic
      parameters. Most selection indices require estimates of economic values, and it
      is often difficult to assign an economic value to a temperament trait. The
      effects of selection primarily for productivity traits on temperament and welfare
      are discussed. Future opportunities include automated data collection methods and
      the wider use of genomic information in selection. 

PMID- 25374584
TI  - Decorin treatment of spinal cord injury.
AB  - The scarring response after a penetrant central nervous system injury results
      from the interaction between invading leptominingeal/pericyte-derived fibroblasts
      and endogenous reactive astrocytes about the wound margin. Extracellular matrix
      and scar-derived axon growth inhibitory molecules fill the lesion site providing
      both a physical and chemical barrier to regenerating axons. Decorin, a small
      leucine-rich chondroitin-dermatan sulphate proteoglycan expressed by neurons and
      astrocytes in the central nervous system, is both anti-fibrotic and anti
      inflammatory and attenuates the formation and partial dissolution of established
      and chronic scars. Here, we discuss the potential of using Decorin to antagonise
      scarring in the central nervous system. 

PMID- 25374583
TI  - Molecular and cellular functions of the FANCJ DNA helicase defective in cancer
      and in Fanconi anemia.
AB  - The FANCJ DNA helicase is mutated in hereditary breast and ovarian cancer as well
      as the progressive bone marrow failure disorder Fanconi anemia (FA). FANCJ is
      linked to cancer suppression and DNA double strand break repair through its
      direct interaction with the hereditary breast cancer associated gene product,
      BRCA1. FANCJ also operates in the FA pathway of interstrand cross-link repair and
      contributes to homologous recombination. FANCJ collaborates with a number of DNA
      metabolizing proteins implicated in DNA damage detection and repair, and plays an
      important role in cell cycle checkpoint control. In addition to its role in the
      classical FA pathway, FANCJ is believed to have other functions that are centered
      on alleviating replication stress. FANCJ resolves G-quadruplex (G4) DNA
      structures that are known to affect cellular replication and transcription, and
      potentially play a role in the preservation and functionality of chromosomal
      structures such as telomeres. Recent studies suggest that FANCJ helps to maintain
      chromatin structure and preserve epigenetic stability by facilitating smooth
      progression of the replication fork when it encounters DNA damage or an alternate
      DNA structure such as a G4. Ongoing studies suggest a prominent but still not
      well-understood role of FANCJ in transcriptional regulation, chromosomal
      structure and function, and DNA damage repair to maintain genomic stability. This
      review will synthesize our current understanding of the molecular and cellular
      functions of FANCJ that are critical for chromosomal integrity. 

PMID- 25374585
TI  - Histological assessment in peripheral nerve tissue engineering.
AB  - The histological analysis of peripheral nerve regeneration is one of the most
      used methods to demonstrate the success of the regeneration through nerve
      conduits. Nowadays, it is possible to evaluate different parameters of nerve
      regeneration by using histological, histochemical, immunohistochemical and
      ultrastructural techniques. The histochemical methods are very sensible and are
      useful tools to evaluate the extracellular matrix remodeling and the myelin
      sheath, but they are poorly specific. In contrast, the immunohistochemical
      methods are highly specific and are frequently used for the identification of the
      regenerated axons, Schwann cells and proteins associated to nerve regeneration or
      neural linage. The ultrastructural techniques offer the possibility to perform a
      high resolution morphological and quantitative analysis of the nerve
      regeneration. However, the use of a single histological method may not be enough
      to assess the degree of regeneration, and the combination of different
      histological techniques could be necessary. 

PMID- 25374586
TI  - Genetic factors for nerve susceptibility to injuries - lessons from PMP22
      deficiency.
AB  - Genetic factors may be learnt from families with gene mutations that render nerve
      injury susceptibility even to ordinary physical activities. A typical example is
      hereditary neuropathy with liability to pressure palsies (HNPP). HNPP is caused
      by a heterozygous deletion of PMP22 gene. PMP22 deficiency disrupts myelin
      junctions (such as tight junction and adherens junctions), leading to abnormally
      increased myelin permeability that explains the nerve susceptibility to injury.
      This finding should motivate investigators to identify additional genetic factors
      contributing to nerve vulnerability of injury. 

PMID- 25374587
TI  - Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury
      by promoting axonal growth and anti-autophagy.
AB  - Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes
      after transplantation in the spinal cord of rats with ischemia/reperfusion
      injury. Although bone marrow mesenchymal stem cells are known to protect against
      spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the
      precise mechanisms remain unclear. In the present study, bone marrow mesenchymal
      stem cells were cultured and proliferated, then transplanted into rats with
      ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and
      immunofluorescence with subsequent quantification revealed that the expression of
      the axonal regeneration marker, growth associated protein-43, and the neuronal
      marker, microtubule-associated protein 2, significantly increased in rats with
      bone marrow mesenchymal stem cell transplantation compared with those in rats
      with spinal cord ischemia/reperfusion injury. Furthermore, the expression of the
      autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1,
      was significantly reduced in rats with the bone marrow mesenchymal stem cell
      transplantation compared with those in rats with spinal cord ischemia/reperfusion
      injury. Western blot analysis showed that the expression of growth associated
      protein-43 and neurofilament-H increased but light chain 3B and Beclin 1
      decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our
      results therefore suggest that bone marrow mesenchymal stem cell transplantation
      promotes neurite growth and regeneration and prevents autophagy. These responses
      may likely be mechanisms underlying the protective effect of bone marrow
      mesenchymal stem cells against spinal cord ischemia/reperfusion injury. 

PMID- 25374588
TI  - Oxidative phosphorylated neurofilament protein M protects spinal cord against
      ischemia/reperfusion injury.
AB  - Previous studies have shown that neurofilament protein M expression is
      upregulated in the early stage of spinal cord ischemia/reperfusion injury,
      indicating that this protein may play a role in the injury process. In the
      present study, we compared protein expression in spinal cord tissue of rabbits
      after 25 minutes of ischemia followed by 0, 12, 24, or 48 hours of reperfusion
      with that of sham operated rabbits, using proteomic two-dimensional gel
      electrophoresis and mass spectrometry. In addition, the nerve repair-related
      neurofilament protein M with the unregulated expression was detected with
      immunohistochemistry and western blot analysis. Two-dimensional gel
      electrophoresis and mass spectrometry showed that, compared with the sham group,
      upregulation of protein expression was most significant in the spinal cords of
      rabbits that had undergone ischemia and 24 hours of reperfusion.
      Immunohistochemical analysis revealed that neurofilament protein M was located in
      the membrane and cytoplasm of neuronal soma and axons at each time point after
      injury. Western blot analysis showed that neurofilament protein M expression
      increased with reperfusion time until it peaked at 24 hours and returned to
      baseline level after 48 hours. Furthermore, neurofilament protein M is
      phosphorylated under oxidative stress, and expression changes were parallel for
      the phosphorylated and non-phosphorylated forms. Neurofilament protein M plays an
      important role in spinal cord ischemia/reperfusion injury, and its functions are
      achieved through oxidative phosphorylation. 

PMID- 25374589
TI  - Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion
      injury.
AB  - Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We
      aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord
      ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We
      established a spinal cord ischemia/reperfusion injury model in rats through the
      occlusion of the abdominal aorta below the level of the renal artery for 1 hour.
      Successfully established models were injected intraperitoneally with 6.25, 12.5,
      25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1,
      3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal
      injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved
      hindlimb motor function and the morphology of motor neurons in the anterior horn
      of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of
      ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after
      ischemia/reperfusion. Immunohistochemistry and western blot analysis showed
      ginsenoside Rd dose-dependently inhibited expression of pro-apoptotic Caspase 3
      and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the
      spinal cord of rats with spinal cord ischemia/reperfusion injury. These findings
      indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord
      ischemia/reperfusion injury and the underlying mechanisms are achieved through
      the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3
      expression. 

PMID- 25374590
TI  - Factors affecting directional migration of bone marrow mesenchymal stem cells to
      the injured spinal cord.
AB  - Microtubule-associated protein 1B plays an important role in axon guidance and
      neuronal migration. In the present study, we sought to discover the mechanisms
      underlying microtubule-associated protein 1B mediation of axon guidance and
      neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid
      or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of
      protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form
      of type I microtubule-associated protein 1B in the cells was greater after
      exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then
      injected the bone marrow mesenchymal stem cells through the ear vein into rabbit
      models of spinal cord contusion. The migration of bone marrow mesenchymal stem
      cells towards the injured spinal cord was poorer in cells exposed to okadaic acid
      and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal
      stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and
      extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow
      mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively.
      LY294002 resulted in an elevated expression of phosphorylated type I microtubule
      associated protein 1B, whereas U0126 caused a reduction in expression. The
      present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells
      modulate the phosphorylation of microtubule-associated protein 1B via a cross
      signaling network, and affect the migratory efficiency of bone marrow mesenchymal
      stem cells towards injured spinal cord. 

PMID- 25374591
TI  - Schwann cells originating from skin-derived precursors promote peripheral nerve
      regeneration in rats.
AB  - Artificial guidance channels containing Schwann cells can promote the
      regeneration of injured peripheral nerve over long distances. However, primary
      Schwann cells are not suitable for autotransplantation. Under specific
      conditions, skin-derived progenitors can be induced to differentiate into Schwann
      cells. Therefore, adult rat dorsal skin (dermis)-derived progenitors were
      isolated and induced to differentiate with DMEM/F12 containing B27, neuregulin 1,
      and forskolin. Immunofluorescence staining and reverse transcription polymerase
      chain reaction (RT-PCR) confirmed that the resultant cells were indeed Schwann
      cells. Artificial guidance channels containing skin-derived progenitors, Schwann
      cells originating from skin-derived progenitors, or primary Schwann cells were
      used to bridge 5 mm sciatic nerve defects. Schwann cells originating from skin
      derived progenitors significantly promoted sciatic nerve axonal regeneration. The
      significant recovery of injured rat sciatic nerve function after the
      transplantation of Schwann cells originating from skin-derived progenitors was
      confirmed by electromyogram. The therapeutic effect of Schwann cells originating
      from skin-derived progenitors was better than that of skin-derived progenitors.
      These findings indicate that Schwann cells originating from skin-derived
      precursors can promote peripheral nerve regeneration in rats. 

PMID- 25374593
TI  - Craniocerebral injury promotes the repair of peripheral nerve injury.
AB  - The increase in neurotrophic factors after craniocerebral injury has been shown
      to promote fracture healing. Moreover, neurotrophic factors play a key role in
      the regeneration and repair of peripheral nerve. However, whether craniocerebral
      injury alters the repair of peripheral nerve injuries remains poorly understood.
      Rat injury models were established by transecting the left sciatic nerve and
      using a free-fall device to induce craniocerebral injury. Compared with sciatic
      nerve injury alone after 6-12 weeks, rats with combined sciatic and
      craniocerebral injuries showed decreased sciatic functional index, increased
      recovery of gastrocnemius muscle wet weight, recovery of sciatic nerve ganglia
      and corresponding spinal cord segment neuron morphologies, and increased numbers
      of horseradish peroxidase-labeled cells. These results indicate that
      craniocerebral injury promotes the repair of peripheral nerve injury. 

PMID- 25374594
TI  - Edaravone promotes functional recovery after mechanical peripheral nerve injury.
AB  - Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve
      injury. However, the therapeutic effect of edaravone on peripheral nerve injury
      caused by mechanical factors is unknown. In the present study, we established a
      peripheral nerve injury model by crushing the sciatic nerve using hemostatic
      forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic
      functional index and superoxide dismutase activity of the sciatic nerve were
      increased, and the malondialdehyde level was decreased in animals in the
      edaravone group compared with those in the model group. Bcl-2 expression was
      increased, but Bax expression was decreased in anterior horn cells of the L4-6
      spinal cord segments. These results indicated that edaravone has a
      neuroprotective effect following peripheral nerve injury caused by mechanical
      factors through alleviating free radical damage to cells and inhibiting lipid
      peroxidation, as well as regulating apoptosis-related protein expression. 

PMID- 25374595
TI  - Sciatic nerve injury repair: a visualized analysis of research fronts and
      development trends.
AB  - A total of 3,446 publications regarding sciatic nerve injury repair and
      protection indexed by Web of Science during 2000-2004 were used for a detailed
      analysis of temporal-spatial distribution characteristics. Reference co-citation
      networks of the 100 top-cited publications as per the number of total citations
      were created using the Web of Science database and the information visualization
      tool, CiteSpaceIII. The key words that showed high frequency in these
      publications were included for analyzing the research fronts and development
      trends for sciatic nerve injury repair and protection. Through word frequency
      trend analysis, studies on bone marrow mesenchymal stem cells, adipose-derived
      stem cells, and skeletal muscle-derived multipotent stem cells combined with
      tissue-engineered scaffold material will become the forefronts in the field of
      sciatic nerve injury repair and protection in the near future. 

PMID- 25374596
TI  - Restoration and protection of brachial plexus injury: hot topics in the last
      decade.
AB  - Brachial plexus injury is frequently induced by injuries, accidents or birth
      trauma. Upper limb function may be partially or totally lost after injury, or
      left permanently disabled. With the development of various medical technologies,
      different types of interventions are used, but their effectiveness is wide
      ranging. Many repair methods have phasic characteristics, i.e., repairs are done
      in different phases. This study explored research progress and hot topic methods
      for protection after brachial plexus injury, by analyzing 1,797 articles
      concerning the repair of brachial plexus injuries, published between 2004 and
      2013 and indexed by the Science Citation Index database. Results revealed that
      there are many methods used to repair brachial plexus injury, and their effects
      are varied. Intervention methods include nerve transfer surgery, electrical
      stimulation, cell transplantation, neurotrophic factor therapy and drug
      treatment. Therapeutic methods in this field change according to the hot topic of
      research. 

PMID- 25374597
TI  - Pyoderma gangrenosum: a review of clinical features and outcomes of 23 cases
      requiring inpatient management.
AB  - Pyoderma gangrenosum (PG) is a rare dermatological disorder characterised by the
      rapid progression of a painful, necrolytic ulcer. This study retrospectively
      identified patients who were admitted and treated for PG during a 10-year period
      (2003-2013). Twenty-three patients were included in this study, 16 women and
      seven men. The mean age at initial admission was 62.8 years (range 30 to 89
      years). Lesions were localised to lower limb in 13 patients, peristomal region in
      four, breast in three, and upper limb in one, and two patients had PG at multiple
      sites. The variants of PG noted were ulcerative (18), bullous (2), vegetative
      (2), and pustular (1). Associated systemic diseases were observed in 11 patients
      (47.8%). Systemic therapies were initiated in 21 patients while two patients
      received topical treatments. The mean length of hospital stay was 47 days (range
      5 to 243 days) and five patients died during their admissions. Seven patients
      required readmissions for exacerbations of their PG. Our study showed that
      patients admitted for treatment of PG had high morbidity and mortality. This
      study also highlights the importance of early and aggressive treatment of
      patients admitted with PG as well as treating associated systemic diseases and
      wound infections. 

PMID- 25374598
TI  - Current iodine nutrition status and awareness of iodine deficiency in tuguegarao,
      Philippines.
AB  - The Philippines is one of the countries where adequate iodine status has been
      achieved. However, iodine deficiency still remains an important public health
      problem in this country. In this study, we evaluated iodine nutrition status and
      investigated an awareness status of iodine deficiency targeting high school
      students of Tuguegarao, Philippines. A total of 260 students provided samples for
      urinary iodine analysis, among which 146 students completed thyroid volume
      measurement by ultrasonography and answering the questionnaires. The median
      urinary iodine level was 355.3 ug/L and only 3.8% of the students were in the
      range of iodine deficiency status according to the ICCIDD criteria. Although
      62.3% of students answered that they can list problems resulting from iodine
      deficiency, a majority of students (70.5%) were unable to identify problems other
      than goiter. They did not appreciate that adequate iodine levels are important
      during pregnancy and for development of children. 33.6% of students answered that
      they did not use iodized salt and the biggest reason was that they did not find
      it necessary. Based on these results, we suggest that a future strategy should be
      focused on vulnerable groups to completely eliminate iodine deficiency, including
      women at their reproductive ages and during pregnancy. 

PMID- 25374599
TI  - Correlation of high-molecular-weight adiponectin and leptin concentrations with
      anthropometric parameters and insulin sensitivity in newborns.
AB  - Objective. High-molecular-weight adiponectin (HMW-adiponectin) and leptin are two
      important adipokines. The aim of this study was to examine the association
      between the two adipokines and anthropometric measurements of neonates at birth.
      Furthermore, we would like to explore whether HMW-adiponectin and leptin
      correlate with insulin sensitivity in neonates. Methods. Venous cord blood
      samples were obtained from 266 full-term healthy neonates consecutively born at
      Peking Union Medical College Hospital. HMW-adiponectin, leptin, blood glucose,
      and insulin concentrations were measured. Results. HMW-adiponectin and leptin
      were significantly higher in females compared with males (P = 0.031 and P =
      0.000, resp.). Univariate correlation analysis showed that leptin concentrations
      in cord blood were positively associated with gestational age, birth weight, body
      length, ponderal index, placenta weight, insulin, and insulin sensitivity (all P
      < 0.001). However, there was no correlation between cord blood HMW-adiponectin
      levels and foetal anthropometric measurements or foetal insulin sensitivity
      indicators (all P > 0.05). Multivariate linear regression analysis indicated that
      leptin (B = -0.126, P = 0.045) in cord blood was independently associated with
      insulin sensitivity. Conclusions. Leptin concentrations, but not HMW-adiponectin,
      were positively associated with foetal anthropometric measurements. Leptin
      concentrations are significantly associated with foetal insulin sensitivity, and
      there were no significant correlations between HMW-adiponectin levels and foetal
      insulin sensitivity. 

PMID- 25374600
TI  - Imaging-cytology correlation of thyroid nodules with initially benign cytology.
AB  - Objective. To determine the role of imaging-cytology correlation in reducing
      false negative results of fine-needle aspiration (FNA) at thyroid nodules.
      Methods. This retrospective study included 667 nodules 1 cm or larger in 649
      patients diagnosed as benign at initial cytologic evaluation and that underwent
      follow-up ultrasound (US) or FNA following a radiologist's opinion on concordance
      between imaging and cytologic results. We compared the risk of malignancy of
      nodules classified into subgroups according to the initial US features and
      imaging-cytology correlation. Results. Among included nodules, 11 nodules were
      proven to be malignant (1.6%) in follow-up FNA or surgery. The malignancy rate
      was higher in nodules with suspicious US features (11.4%) than in nodules without
      suspicious US features (0.5%, P < 0.001). When a thyroid nodule had discordant US
      findings on image review after having benign FNA results, malignancy rate
      increased to 23.3%, significantly higher than that of nodules with suspicious US
      features (P < 0.001). However, no significant difference was found in the risk of
      malignancy between the nodules without suspicious US features (0.5%) and imaging
      cytology concordant nodules (0.6%, P = 0.438). Conclusions. Repeat FNA can be
      effectively limited to patients with cytologically benign thyroid nodules showing
      discordance in imaging-cytology correlation after initial biopsy, which reduces
      unnecessary repeat aspirations. 

PMID- 25374601
TI  - Changes in coagulation and fibrinolytic indices in women with polycystic ovarian
      syndrome undergoing controlled ovarian hyperstimulation.
AB  - Background. Polycystic ovarian syndrome (PCOS) women undergoing in vitro
      fertilization and embryo transfer (IVF-ET) treatment always attain a low
      cumulative pregnancy rate disaccording with the satisfactory number of oocytes.
      Objective. We aim to evaluate the status of coagulation and fibrinolytic system
      in PCOS patients undergoing controlled ovarian hyperstimulation (COH) process.
      Method. Of the 97 women, 30 patients with PCOS composed the study group; 67 women
      of child-bearing age with normal endocrine function composed the control group.
      All participants underwent GnRH agonist standard long protocol, and plasma HCY,
      FVIII, FX, and D-dimer levels as well as hormone parameters were measured at day
      of full downregulation, hCG priming, and embryos transfer. Results. On day of
      full downregulation, FX levels were significantly higher in PCOS group (P <
      0.01). On hCG priming day, FX and estrogen levels in PCOS group were higher than
      in the control group and FVIII levels were significantly lower on day of embryos
      transfer whereas FX and E2 levels were significantly higher in PCOS group.
      Conclusion. Hypercoagulable state during peri-implantation phase would probably
      lead to poor microcirculation of endometrium and be one of the most important
      disadvantages of successful implantation and subsequent clinical pregnancy. 

PMID- 25374603
TI  - Photoelastic analysis of fixed partial prosthesis crown height and implant length
      on distribution of stress in two dental implant systems.
AB  - The aim of this study was to evaluate by photoelastic analysis stress
      distribution on short and long implants of two dental implant systems with 2-unit
      implant-supported fixed partial prostheses of 8 mm and 13 mm heights. Sixteen
      photoelastic models were divided into 4 groups: I: long implant (5 * 11 mm)
      (Neodent), II: long implant (5 * 11 mm) (Bicon), III: short implant (5 * 6 mm)
      (Neodent), and IV: short implants (5 * 6 mm) (Bicon). The models were positioned
      in a circular polariscope associated with a cell load and static axial (0.5 Kgf)
      and nonaxial load (15 degrees , 0.5 Kgf) were applied to each group for both
      prosthetic crown heights. Three-way ANOVA was used to compare the factors implant
      length, crown height, and implant system (alpha = 0.05). The results showed that
      implant length was a statistically significant factor for both axial and nonaxial
      loading. The 13 mm prosthetic crown did not result in statistically significant
      differences in stress distribution between the implant systems and implant
      lengths studied, regardless of load type (P > 0.05). It can be concluded that
      short implants showed higher stress levels than long implants. Implant system and
      length was not relevant factors when prosthetic crown height were increased. 

PMID- 25374604
TI  - Field dissipation and storage stability of glufosinate ammonium and its
      metabolites in soil.
AB  - A simple analytical method was developed to measure concentrations of glufosinate
      ammonium and its metabolites, 3-methylphosphinico-propionic acid (MPP) and 2
      methylphosphinico-acetic acid (MPA), in field soil samples. To determine the
      minimum quantification limit, samples were spiked at different levels (0.1, 0.5,
      and 1.0 mg/kg). Soil samples were extracted with ammonium hydroxide solution 5%
      (v/v), concentrated, and reacted with trimethyl orthoacetate (TMOA) in the
      presence of acetic acid for derivatization. The derivatives were quantified by
      gas chromatography (GC) using a flame photometric detector (FPD). The linear
      correlation coefficients of glufosinate ammonium, MPP, and MPA in soil were
      0.991, 0.999, and 0.999, respectively. The recoveries of this method for
      glufosinate ammonium, MPP, and MPA in soil were 77.2-95.5%, 98.3-100.3%, and 99.3
      99.6% with relative standard deviations (RSD) of 1.8-4.1%, 0.4-1.4%, and 1.3
      2.0%, respectively. Glufosinate ammonium dissipated rapidly in soil to MPA in
      hours and gradually degraded to MPP. The half-life of glufosinate ammonium
      degradation in soil was 2.30-2.93 days in an open field. In soil samples stored
      at -20 degrees C glufosinate ammonium was stable for two months. The results of
      this study should provide guidance for the safe application of the herbicide
      glufosinate ammonium to agricultural products and the environment. 

PMID- 25374602
TI  - Autoimmune and neoplastic thyroid diseases associated with hepatitis C chronic
      infection.
AB  - Frequently, patients with hepatitis C virus (HCV) chronic infection have high
      levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies,
      ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical
      hypothyroidism, in female gender versus healthy controls, or hepatitis B virus
      infected patients. In patients with "HCV-associated mixed cryoglobulinemia" (MC +
      HCV), a higher prevalence of thyroid autoimmune disorders was shown not only
      compared to controls, but also versus HCV patients without cryoglobulinemia.
      Patients with MC + HCV or HCV chronic infection show a higher prevalence of
      papillary thyroid cancer than controls, in particular in patients with autoimmune
      thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence
      of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C
      motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand
      2 chemokine, than patients without thyroiditis. HCV thyroid infection could act
      by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1
      lymphocytes that secrete interferon-gamma and tumor necrosis factor-alpha. These
      cytokines might induce a further CXCL10 secretion by thyrocytes, thus
      perpetuating the immune cascade, which may lead to the appearance of autoimmune
      thyroid disorders in genetically predisposed subjects. A careful monitoring of
      thyroid function, particularly where nodules occur, is recommended in HCV
      patients. 

PMID- 25374605
TI  - Effect of preoperative mastoid ventilation on tympanoplasty success.
AB  - Purpose. This study was conducted with the aim of investigating the relationship
      between mastoid air cell volumes and graft success after tympanoplasty. Material
      and Methods. This study was performed retrospectively with patients undergoing
      type I tympanoplasty and antrostomy. A total of 57 patients (20-35.09% female and
      37-64.91% male) with a mean age of 29.69 +/- SD (range 12-56 years) were included
      in the study. The patients were invited for a control at the 1st, 3rd, and 12th
      months, and otoscopic examinations and audiometric tests were performed. The
      temporal bone computed tomography images were screened with the 4800 Dpi optic
      resolution scanner and transferred to the computer environment in JPG format in
      order to calculate the mastoid air cell volume, and the volumes were calculated
      using the Autocad 2007 program. Results. Although, the graft success was
      determined to be better in the well-ventilated group, no significant difference
      could be found between the groups in terms of graft success at the 1st, 3rd, and
      12th months (P > 0.05). No statistically significant difference could be found
      between the three groups in terms of the preoperative and postoperative hearing
      gains (P > 0.05). 

PMID- 25374606
TI  - Noninvasive Recording of True-to-Form Fetal ECG during the Third Trimester of
      Pregnancy.
AB  - Objective. The aim of the study was to develop a complex electrophysiological
      measurement system (hardware and software) which uses the methods of
      electrophysiology and provides significant information about the intrauterine
      status of the fetus, intending to obtain true-to-form, morphologically evaluated
      fetal ECG from transabdominal maternal lead. Results. The present method contains
      many novel ideas that allow creating true-to-form noninvasive fetal ECG in the
      third trimester of the pregnancy in 80% of the cases. Such ideas are the
      telemetric data collection, the "cleanse" of the real time recording from the
      maternal ECG, and the use of the cardiotocograph (CTG) that allows identifying
      the fetal heart events. The advantage of this developed system is that it does
      not require any qualified staff, because both the extraction of the information
      from the abdominal recording and the processing of the data are automatic.
      Discussion. Although the idea of a noninvasive fetal electrocardiography is more
      than 100 years old still there is no simple, effective, and cheap method
      available that would enable an extensive use. This developed system can be used
      in the third trimester of the pregnancy efficiently. It can produce true-to-form
      fetal ECGs with amplitude less than 10 uV. 

PMID- 25374607
TI  - Does polycystic ovary syndrome itself have additional effect on apelin levels?
AB  - Objective. The present study was designed to compare serum levels of apelin
      between lean PCOS women and healthy women with regular menses. Study Design. A
      total of 30 lean patients with PCOS and 30 healthy subjects were included in this
      study. Serum apelin levels were compared between groups. Results. Serum apelin
      levels in lean PCOS patients were not significantly different from the control
      subjects. Conclusion. Our findings indicate that PCOS itself does not seem to
      change apelin levels. Further investigation on a large number of subjects will
      need to be conducted to prove the consistent or variable association in PCOS. 

PMID- 25374608
TI  - Prevalence of nocturnal enuresis and its associated factors in primary school and
      preschool children of khorramabad in 2013.
AB  - Background. Nocturnal enuresis refers to an inability to control urination during
      sleep. This study aimed to determine the prevalence of nocturnal enuresis and its
      associated factors in children in the city of Khorramabad. Materials and Methods.
      In this descriptive-analytic, cross-sectional study, 710 male and female children
      were divided into two groups with equal numbers. The samples were selected from
      the schools of Khorramabad using the multistage cluster and stratified random
      sampling methods based on the diagnostic criteria of DSM-IV. The data was
      analyzed using the logistic regression. Results. The results showed that 8% of
      the children had nocturnal enuresis, including 5.2% of primary nocturnal enuresis
      and 2.8% of secondary nocturnal enuresis. The prevalence of nocturnal enuresis in
      the boys (10.7%) was higher compared with that in the girls (5.4%) (P = 0.009).
      There were statistically significant relationships between nocturnal enuresis and
      history of nocturnal enuresis in siblings (P = 0.023), respiratory infections (P
      = 0.036), deep sleep (P = 0.007), corporal punishment at school (P = 0.036), anal
      itching (P = 0.043), and history of seizures (P = 0.043). Conclusion. This study
      showed that the prevalence of nocturnal enuresis in the boys was higher compared
      with that in the girls. 

PMID- 25374609
TI  - INFRASTRUCTURAL MECHANISMS LEADING TOWARD PRO-ACCOUNTABLE CARE ORGANISATION
      ORIENTATION: A SURVEY OF HOSPITAL MANAGERS.
AB  - Organisations across the country are transforming the way they deliver care, in
      ways similar to the accountable care organisation (ACO) model supported by
      Medicare. ACOs modalities are varying in size, type, and financing structure.
      Little is known about how specific infrastructural mechanisms influence hospital
      managers' pro-ACO orientation. Using an electronic-survey of hospital managers,
      this study explores how pro-ACO orientation, as a latent construct, is captured
      from the perceptions of hospital managers; and identify infrastructural
      mechanisms leading to the formation of pro-ACO orientation. Of the total hospital
      respondents, 58% are moving toward the establishment of ACOs; 56% are planning to
      join in the next two years; 48% are considering joining ACOs; while 25% had
      already participated in ACOs during 2012. Urban hospitals are more likely than
      rural hospitals to be engaged in ACO development. The health provider network
      size is one of the strongest indicators in predicting pro-ACO orientation.

PMID- 25374610
TI  - Enhancing epidemiological analysis of intercontinental dispersion of H5N1 viral
      strains by migratory waterfowl using phylogeography.
AB  - BACKGROUND: Intercontinental migratory waterfowl are the primary vectors for
      dispersion of H5N1 viruses and have been implicated in several zoonotic epidemics
      and pandemics. Recent investigations have established that with a single
      mutation, the virus gains the ability to transmit between humans. Consequently,
      there is a heightened urgency to identify innovative approaches to proactively
      mitigate emergent epidemics. Accordingly, a novel methodology combining temporo
      geospatial epidemiology and phylogeographic analysis of viral strains is proposed
      to identify critical epicenters and epidemic pathways along with high risk
      candidate regions for increased surveillance. RESULTS: Epidemiological analysis
      was used to identify 91,245 candidate global infection transmission pathways
      between 22 high risk waterfowl species. Dominant infection pathways (25,625 and
      54,500 in summering and wintering zones) were identified through annotation using
      phylogeographical data computed from the phylogram of 2417 H5N1 HA isolates (from
      GISAID EpiFlu database). Annotation of infection pathways in turn delineated 23
      influential clades out of 130 clades in the phylogram. CONCLUSIONS: The
      phylogeographic analyses provides strong cross-validation of epidemic pathways
      and identifies the dominant pathways for use in other epidemiological and
      prophylactic studies. The temporo-geospatial characteristics of infection
      transmission provides corroborating, but novel evidence for rapid genesis of H5N1
      lineages in S.E. Asia. The proposed method pinpoints several regions,
      particularly in the southern hemisphere, as candidates for increased
      surveillance.

PMID- 25374611
TI  - Classification models for clear cell renal carcinoma stage progression, based on
      tumor RNAseq expression trained supervised machine learning algorithms.
AB  - BACKGROUND: Clear-cell Renal Cell Carcinoma (ccRCC) is the most- prevalent,
      chemotherapy resistant and lethal adult kidney cancer. There is a need for novel
      diagnostic and prognostic biomarkers for ccRCC, due to its heterogeneous
      molecular profiles and asymptomatic early stage. This study aims to develop
      classification models to distinguish early stage and late stage of ccRCC based on
      gene expression profiles. We employed supervised learning algorithms- J48, Random
      Forest, SMO and Naive Bayes; with enriched model learning by fast correlation
      based feature selection to develop classification models trained on sequencing
      based gene expression data of RNAseq experiments, obtained from The Cancer Genome
      Atlas. RESULTS: Different models developed in the study were evaluated on the
      basis of 10 fold cross validations and independent dataset testing. Random Forest
      based prediction model performed best amongst the models developed in the study,
      with a sensitivity of 89%, accuracy of 77% and area under Receivers Operating
      Curve of 0.8. CONCLUSIONS: We anticipate that the prioritized subset of 62 genes
      and prediction models developed in this study will aid experimental oncologists
      to expedite understanding of the molecular mechanisms of stage progression and
      discovery of prognostic factors for ccRCC tumors.

PMID- 25374612
TI  - Characteristics of equipartition for RNA structure.
AB  - BACKGROUND: With the continuous discovery of novel RNA molecules with key
      cellular functions and of novel pathways and interaction networks, the need for
      structural information of RNA is still increasing. In order to predict structure
      of long RNA and understand its natural folding mechanism, exploring the
      characteristic of RNA structure is an important issue. METHODS: The real RNA
      secondary structures of all 480 sequences from the database of RNA strand,
      validated by nuclear magnetic resonance or x-ray are selected. For one sequence
      with multiple domains, the length ratios of these domains to the sequence are
      computed. For one sequence with one domain and multiple sub-domains, the length
      ratios of these sub-domains to the domain are computed. Then the ratios are
      compared and analyzed to seek the partition characteristic of domains and
      subdomains. RESULTS: For most RNAs, the length ratios of multiple domains to its
      sequence are close to equal, and those of sub-domains to its domain are also
      nearly identical. Most RNAs with multiple domains have two domains, so the length
      ratios of the domains to its sequence are close to 0.5. For sequence with one
      domain and no sub-domain or one sub-domain, the centre of domain and sub-domain
      is close to that of the sequence. CONCLUSIONS: A novel finding is given that RNA
      folding accords with the characteristic of equipartition based on statistical
      analysis. The characteristic reflects the folding rules of RNA from a new angle,
      which maybe more close to natural folding.

PMID- 25374613
TI  - Identifying common components across biological network graphs using a bipartite
      data model.
AB  - The GeneWeaver bipartite data model provides an efficient means to evaluate
      shared molecular components from sets derived across diverse species, disease
      states and biological processes. In order to adapt this model for examining
      related molecular components and biological networks, such as pathway or gene
      network data, we have developed a means to leverage the bipartite data structure
      to extract and analyze shared edges. Using the Pathway Commons database we
      demonstrate the ability to rapidly identify shared connected components among a
      diverse set of pathways. In addition, we illustrate how results from maximal
      bipartite discovery can be decomposed into hierarchical relationships, allowing
      shared pathway components to be mapped through various parent-child relationships
      to help visualization and discovery of emergent kernel driven relationships.
      Interrogating common relationships among biological networks and conventional
      GeneWeaver gene lists will increase functional specificity and reliability of the
      shared biological components. This approach enables self-organization of
      biological processes through shared biological networks. 

PMID- 25374614
TI  - Reconstruction of metabolic pathways by combining probabilistic graphical model
      based and knowledge-based methods.
AB  - Automatic reconstruction of metabolic pathways for an organism from genomics and
      transcriptomics data has been a challenging and important problem in
      bioinformatics. Traditionally, known reference pathways can be mapped into an
      organism-specific ones based on its genome annotation and protein homology.
      However, this simple knowledge-based mapping method might produce incomplete
      pathways and generally cannot predict unknown new relations and reactions. In
      contrast, ab initio metabolic network construction methods can predict novel
      reactions and interactions, but its accuracy tends to be low leading to a lot of
      false positives. Here we combine existing pathway knowledge and a new ab initio
      Bayesian probabilistic graphical model together in a novel fashion to improve
      automatic reconstruction of metabolic networks. Specifically, we built a
      knowledge database containing known, individual gene / protein interactions and
      metabolic reactions extracted from existing reference pathways. Known reactions
      and interactions were then used as constraints for Bayesian network learning
      methods to predict metabolic pathways. Using individual reactions and
      interactions extracted from different pathways of many organisms to guide pathway
      construction is new and improves both the coverage and accuracy of metabolic
      pathway construction. We applied this probabilistic knowledge-based approach to
      construct the metabolic networks from yeast gene expression data and compared its
      results with 62 known metabolic networks in the KEGG database. The experiment
      showed that the method improved the coverage of metabolic network construction
      over the traditional reference pathway mapping method and was more accurate than
      pure ab initio methods. 

PMID- 25374615
TI  - Innovation in e-learning: learning for all.
AB  - Online learning is not a new concept for most in the medical profession. However,
      surgical oncology is poorly represented, and in a world of ever-changing research
      evidence, relying on published texts may not be efficient learning or an accurate
      representation of current practice for many trainees. This article demonstrates
      how our educational collaborative, ePOSSOM, approaches the problem. It outlines
      the development process of the whole project between ecancer and the Severn
      School of Surgery, UK, and provides links to the pilot completed modules on
      pancreatic cancer and its treatment for the reader to experience. 

PMID- 25374616
TI  - Leptomeningeal carcinomatosis associated with papillary renal cell carcinoma.
AB  - Leptomeningeal carcinomatosis (LMC), or neoplastic meningitis, occurs in about 5
      20% of patients with metastatic cancer, depending on the type of the primary
      malignancy and kind of treatment received. The association of LMC with renal cell
      carcinoma (RCC) is a rare entity, and only two cases of papillary renal cell
      cancer with leptomeningeal metastasis have been reported. Leptomeningeal spread
      usually confers a poor prognosis despite the use of modern treatment strategies
      as compared to patients with extracranial metastases. We report a case of
      papillary RCC, a less common type of RCC presenting with LMC. 

PMID- 25374617
TI  - IMRT, RapidArc(r) and conformal radiotherapy in the treatment of tumours of the
      anal canal.
AB  - PURPOSE: To compare dosimetric results of the use of RapidArc(r) with
      simultaneous integrated boost, sliding window intensity-modulated radiotherapy
      (IMRT) with simultaneous integrated boost, and conformal radiotherapy with
      sequential boost in the management of anal canal cancer. METHODS: Two patients
      with squamous cell cancer of the anal canal with compromised inguinal nodes were
      included. The simulation was performed in the supine position with a customized
      Vac-LokTM immobilizer. Treatment volumes and organs at risk were defined in
      accordance with international recommendations. Dosimetric comparisons were made
      in the target volume by means of tumour conformity, coverage, and homogeneity
      indexes; in healthy organs, integral doses were compared. RESULTS: A similar
      planning target volume coverage was achieved with the three techniques. The two
      IMRT techniques demonstrated benefits in doses received by healthy organs
      compared to the conformal radiotherapy. RapidArc(r) showed reduction in the
      execution time and monitor units required for treatment compared with sliding
      window IMRT. CONCLUSIONS: The IMRT showed coverage and tumour conformity indexes
      similar to those of conformal radiotherapy with better dosimetric results in the
      organs at risk, which should translate into a better toxicity profile.
      RapidArc(r) demonstrated benefits over the sliding window IMRT, which makes
      treatment more comfortable for the patient with less uncertainty about
      intrafraction motion and a reduced potential for radiation-induced tumours.

PMID- 25374618
TI  - Oncoplastic breast surgery: initial experience at the Centro Clinico de
      Estereotaxia-CECLINES, Caracas, Venezuela.
AB  - BACKGROUND: Breast-conserving surgery (BCS) may sometimes lead to deformities in
      the remaining breast. Oncoplastic surgery (OPS) aims to improve our aesthetic
      results even in the case of major volume resections. The purpose of this study is
      to provide an objective evaluation of our initial experience with OPS, mainly
      based on the levels of satisfaction reported by both patients and surgeons.
      PATIENTS AND METHODS: This prospective study was performed at CECLINES in
      Caracas, Venezuela, between January 2011 and October 2012. It involved 107
      consecutive patients in two groups: 52 patients with level II OPS versus 55
      patients with 'standard' BCS (SBCS). We evaluated the level of satisfaction and
      cosmetic outcome at 6 and 12 months post-operation using a score from 1 (bad) to
      5 (excellent). The cosmetic score was recorded during the follow-up by the
      surgeon, by phone calls, and photographs were reviewed by a panel of four
      observers. RESULTS: The participation rate in the cosmetic outcome/level of
      satisfaction evaluation was 100% at 6 months and 96.2% at 12 months. The average
      tumour size was 23 mm [standard deviation (SD): 13.5] for the OPS group versus
      17.6 mm (SD: 8.3) for the SBCS group (p = 0.017). The average weight for the
      surgical specimen was 101 g (range: 30-512 g) in the OPS group versus 60.4 g
      (range: 20-135 g) in the SBCS group (p = 0.004). The OPS techniques most
      performed were round block 40.3% (21/52), inverted T mammoplasty 26.8% (14/52)
      and vertical scar mammoplasty 15.3% (8/52). Of all the patients, 51.9% (27/52)
      had symmetrisation procedures performed distributed according to the period of
      the study: 77.2% (17/22) in 2011, 56.6% (17/30) in 2012, and 18.1% (6/33) in
      2013. The rate of complications was 5.7% (3/52) in the OPS group and 0% for the
      SBCS group (p < 0.005). The average cosmetic score at 6 months by patients in the
      OPS group was 4.4; patient satisfaction scores of 4 (good) and 5 (excellent) were
      88.4%. In the SBCS group at 6 months, the mean score reported by patients was
      4.2, with scores 4-5 being 83.4% (p = 0.644). The cosmetic score by surgeons in
      the OPS group at 6 months was 4.5; the surgeon satisfaction scores of 4-5 were
      94.2%. In the SBCS group, the surgeons' mean score at 6 months was 4.1, with
      84.5% of scores being 4 or 5 (p < 0.005). The final cosmetic score by patients in
      the OPS group at 12 months was 4.5; patient satisfaction scores of 4-5 were
      90.4%. In the SBCS group, the final mean score at 12 months by patients was 4.2,
      with 77.5% of scores being 4 or 5 (p < 0.005). The final cosmetic score by
      surgeons in the OPS group at 12 months was 4.5; surgeon satisfaction scores of 4
      5 were 92.3%. In the SBCS group, the surgeons' final mean score at 12 months was
      4.1, with 84.5% of scores being 4 or 5 (p < 0.005). CONCLUSIONS: OPS provides
      good satisfaction rates. An SBCS when an OPS is not indicated mostly results in
      good satisfaction levels and cosmetic scores. Usually, the results remain stable
      after 6 months. The use of OPS allows the excision of bigger lesions and surgical
      specimens. Symmetrisation procedures are not always required. With the
      appropriate patient selection, the rate of complications is low for both OPS and
      SBCS.

PMID- 25374619
TI  - Juvenile psammomatoid ossifying fibroma with aneurysmal bone cyst in the
      posterior mandible.
AB  - Aneurysmal bone cysts (ABCs) are a rare benign lesion seen as locally
      destructive, rapidly expansile, and mostly affecting the long bones and
      vertebrae. The association of ABCs with juvenile psammomatoid ossifying fibroma
      (PsJOF) is predominantly seen in the extragnathic region, and it is extremely
      rare with only a few cases reported so far in the mandible. Here, we report one
      such case of a hybrid lesion in a seven-year-old boy, who presented with a
      solitary swelling of the left mandible showing partial obliteration of buccal
      vestibular sulcus, which shows juvenile psammomatoid ossifying fibroma as a pre
      exsiting lesion, transforming into an ABC. Such hybrid lesions are usually
      misdiagnosed and have been sparsely reported in the dental literature. 

PMID- 25374620
TI  - From precision medicine to cancer care through the immunome: highlights from the
      European Society of Medical Oncology Congress, Madrid, 26-30th September 2014.
AB  - The recognition that cancer is a 'spectrum' of diseases, and that medical
      oncologists should achieve 'convergence' from 'divergence' to treat cancer
      patients was the main theme of the 2014 European Society of Medical Oncology
      (ESMO) Congress. The meeting assembled 19,859 participants from nearly 134
      countries worldwide. The educational content was centered on precision medicine
      in cancer care, from mutational burden to the immunome, through the epigenome and
      the proteome. Precision medicine has been defined as the tailoring of medical
      treatment to the characteristics of an individual patient. Knowing an
      individual's genomics has created a remarkable and unprecedented opportunity to
      improve medical treatment and develop preventative strategies to preserve health.
      Clinical oncologists across the range of diseases recognise that for precision
      medicine to take hold, it will require intensive, rigorous validation that these
      new approaches do indeed improve patient outcomes. Not all molecular alterations
      are predictive of response to a specific targeted treatment nor are they all
      druggable, raising issues of cost-benefit, validation of specific biomarkers, and
      of managing patient expectations. Addressing all these issues will be essential
      for the medical community to embrace any given opportunities. Along with it, it
      will also require educational programmes that squarely address the knowledge
      chasm that currently exists for practicing physicians. The promise of genomic and
      precision medicine has created greater demands for both those providing the
      scientific expertise-bioinformatics, statisticians, molecular biologists-and
      those delivering clinical care-physicians, nurses, psychologists-to the patients.
      This ESMO 2014 report will highlight the major findings of this outstanding
      meeting. 

PMID- 25374621
TI  - Common genetic variants in pre-microRNAs and risk of breast cancer in the North
      Indian population.
AB  - OBJECTIVE: MicroRNAs (miRNAs) are short regulatory RNAs that can modulate gene
      expression and function as negative regulators. Common genetic variants like
      single nucleotide polymorphisms (SNPs) in miRNA genes may alter their expression
      or maturation resulting in varied functional consequences in carcinogenesis.
      Therefore, we evaluated the genetic variants in pre-miRNAs: hsa-miR-146a G/C
      (rs2910164), hsa-miR-196a2 C/T (rs11614913), and hsa-miR-499 T>C (rs3746444) for
      their role in breast cancer susceptibility. STUDY DESIGN: The study comprised 121
      breast cancer patients, 115 with benign breast disease, and 164 controls. The
      genotypic frequency of miRNA polymorphisms was determined by PCR-RFLP assay.
      Logistic regression was used for statistical analysis using SPSS Software version
      15.0. In silico analysis was done using various bioinformatics tools (F-SNP, FAST
      SNP). RESULTS: The heterozygous variant of miR-146a G/C (rs2910164) is associated
      with the reduced risk of breast cancer at the genotype level as well as at the
      allele level (p < 0.05, OR = 0.5) as compared to controls. On the contrary, no
      significant difference was observed in the distribution of miR-196a2 C/T
      (rs11614913) and miR-499 T>C (rs3746444) polymorphisms in any groups both at
      genotype and allele levels. On the other hand, in multivariate analysis, we found
      that the miR-196a2 (rs11614913) C>T was associated with an increased risk of
      breast cancer risk in postmenopausal females (p = 0.02, OR = 3.2). We also
      attempted to find out the risk of malignant breast disease in relation to each of
      the above SNPs on dividing our data on the basis of benign and malignant status,
      but no significant difference was observed. In silico analysis using F-SNP showed
      change in transcriptional regulation by miR-146a G/C (rs2910164), miR-196a2 C/T
      (rs11614913) and miR-499 T>C (rs3746444) variations; the functional score was
      0.100, 0.065 and 0.277, respectively. CONCLUSION: The results of the present
      study demonstrate that miR-146a G/C (rs2910164) polymorphism is associated with
      reduced genetic susceptibility to breast cancer. However, multivariate analysis
      showed as miR-196a2 (rs11614913) C>T to be associated with increased risk of
      breast cancer risk in postmenopausal females. Further multicentric studies
      involving a large number of cases need to be carried out to strengthen the
      present results.

PMID- 25374622
TI  - Primary cardiac lymphoma with isolated parenchymal central nervous system
      relapse: report of two cases and review of the literature.
AB  - Primary cardiac lymphoma (PCL) is a rare subset of non-Hodgkin's lymphoma
      involving the heart and/or pericardium with no or minimal evidence of
      extracardiac involvement at presentation. Distant relapses have infrequently been
      observed. We report two cases of this disorder that showed isolated central
      nervous system (CNS) relapse. Diagnosis by endomyocardial biopsy was consistent
      with diffuse large B-cell lymphoma. After immunochemotherapy they achieved
      complete remission (CR). Eight and five weeks after, isolated CNS relapses were
      observed respectively. The first patient was treated with high-dose methotrexate
      (HD-MTX) and high-dose cytarabine, resulting in a second CR. She then went onto
      receive autologous stem-cell transplantation but unfortunately died shortly after
      because of infection. The second patient received systemic CNS prophylaxis with
      HD-MTX, and later she was treated with an induction chemotherapy strategy with
      evidencing of progressive disease after two courses of treatment. She was
      subsequently initiated on a salvage therapy with cytarabine, followed by whole
      brain radiotherapy, and autologous stem-cell transplant (ASCT), finally achieving
      a complete remission. Isolated CNS relapse is a very uncommon pattern in PCL and
      a standard approach to treatment is not yet well established. Nevertheless, the
      importance of CNS evaluation, using magnetic resonance imaging (MRI) and lumbar
      puncture, in patients with PCL should be considered, and further studies are
      recommended to determine the appropriate management of this complication. 

PMID- 25374623
TI  - Human papillomavirus detection in head and neck squamous cell carcinoma.
AB  - INTRODUCTION: Human Papillomavirus (HPV) has been associated with benign and
      malignant lesions in different epitheliums. The relationship between specific
      genotypes of high-risk HPV and some human cancers is well established. The aim of
      this work was to detect the HPV genotypes present in head and neck squamous cell
      carcinoma (HNSCC). METHODS: We evaluated 71 samples of patients with
      histopathological diagnosis of HNSCC. The DNA extraction was conducted with the
      QIAGEN commercial kit. HPV detection and genotyping were performed by reverse
      hybridisation (INNO-LiPA) following the commercial specifications. RESULTS: The
      mean age of the patients evaluated was 60.7 +/- 13.11 years. The distribution of
      the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the
      oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of
      paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients,
      78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol
      consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity
      and the larynx were the highest HPV-positivity sites with 35.40% and 29.10%
      respectively. The most frequent genotype was 16 as single infection (18.70%), or
      in combination with another HPV types. In the oral cavity and larynx the
      genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%,
      respectively; and in the oropharynx the most frequent genotype was 16 in 22.50%
      of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We
      observed that tumours with most advanced size and stage presented greater HPV
      positivity. CONCLUSIONS: This study shows a high percentage of HPV positivity in
      SCC is mainly associated with high-risk HPV. It is important to highlight that
      viral infection, especially HPV-16, could be a risk factor in HNSCC progression.

PMID- 25374624
TI  - Cancer research: quo vadis-to war?
AB  - The notion that we should wage all-out war on cancer to break the back of the
      problem is considered fundamentally untenable because of the inherent nature of
      the disorder. An alternative is argued on the basis that we can only achieve a
      greater degree of control through attrition, since only a minority of tumour
      types might truly be curable in many cases. 

PMID- 25374626
TI  - Magnetic resonance imaging of rotator cuff tears in shoulder impingement
      syndrome.
AB  - BACKGROUND: Shoulder joint is a common site of musculoskeletal pain caused, among
      other things, by rotator cuff tears due to narrowing of subacromial space, acute
      trauma or chronic shoulder overload. Magnetic resonance imaging (MRI) is an
      excellent modality for imaging of soft tissues of the shoulder joint considering
      a possibility of multiplanar image acquisition and non-invasive nature of the
      study. The aim of this study was to evaluate the prevalence of partial and
      complete rotator cuff tears in magnetic resonance images of patients with
      shoulder impingement syndrome and to review the literature on the causes and
      classification of rotator cuff tears. MATERIAL/METHODS: We retrospectively
      analyzed the results of 137 shoulder MRI examinations performed in 57 women and
      72 men in Magnetic Resonance facility of the Department of Radiology and
      Diagnostic Imaging at the St. Jadwiga the Queen Regional Hospital No. 2 in
      Rzeszow between June 2010 and February 2013. Examinations were performed using
      Philips Achieva 1.5T device, including spin echo and gradient echo sequences with
      T1-, T2- and PD-weighted as well as fat saturation sequences in transverse,
      frontal and sagittal oblique planes. Patients were referred from hospital wards
      as well as from outpatient clinics of the subcarpathian province. RESULTS: The
      most frequently reported injuries included partial supraspinatus tendon tear and
      complete tearing most commonly involved the supraspinatus muscle tendon. The
      smallest group comprised patients with complete tear of subscapularis muscle
      tendon. Among 137 patients in the study population, 129 patients suffered from
      shoulder pain, including 57 patients who reported a history of trauma. There was
      44% women and 56% men in a group of patients with shoulder pain. Posttraumatic
      shoulder pain was predominantly reported by men, while women comprised a larger
      group of patients with shoulder pain not preceded by injury. CONCLUSIONS: Rotator
      cuff injury is a very common pathology in patients with shoulder impingement
      syndrome. Isolated supraspinatus tendon injury or complete tearing is most
      frequent, rather than in conjunction with injuries to other rotator cuff tendons.
      We did not observe isolated complete tears of infraspinatus and subscapular
      muscle tendons.

PMID- 25374627
TI  - [Retinal fold].

PMID- 25374625
TI  - Monogenic causes of elevated HDL cholesterol and implications for development of
      new therapeutics.
AB  - Identification of the CETP, LIPG (encoding endothelial lipase) and APOC3 genes,
      and ana lysis of rare genetic variants in them, have allowed researchers to
      increase understanding of HDL metabolism significantly. However, development of
      cardiovascular risk-reducing therapeutics targeting the proteins encoded by these
      genes has been less straightforward. The failure of two CETP inhibitors is
      complex but illustrates a possible over-reliance on HDL cholesterol as a marker
      of therapeutic efficacy. The case of endothelial lipase exemplifies the
      importance of utilizing population-wide genetic studies of rare variants in
      potential therapeutic targets to gain information on cardiovascular disease end
      points. Similar population-wide studies of cardiovascular end points make apoC
      III a potentially attractive target for lipid-related drug discovery. These three
      cases illustrate the positives and negatives of single-gene studies relating to
      HDL-related cardiovascular drug discovery; such studies should focus not only on
      HDL cholesterol and other components of the lipid profile, but also on the effect
      genetic variants have on cardiovascular end points.

PMID- 25374628
TI  - [Surgical treatment of acetabular fractures: report of 22 cases].

PMID- 25374629
TI  - [Proliferative diabetic retinopathy: dreaded stage leading to blindness].

PMID- 25374630
TI  - [Profile of diabetic in chronic hemodialysis: a multicenter study in Morocco].

PMID- 25374631
TI  - [Concordance and contributions of hysterosalpingography and laparoscopy in
      exploration of pelvic and tubal infertility].

PMID- 25374632
TI  - [Closed kidney trauma: about 55 observations].

PMID- 25374633
TI  - [Osteochondritis dissecans of the capitellum in adolescents: report of a case and
      review of the literature].

PMID- 25374634
TI  - [Massive pleural effusion after surgery of breast cancer and early
      discontinuation of tamoxifen: about an observation].

PMID- 25374635
TI  - [Papillary alterations in high myopia].

PMID- 25374636
TI  - Askin tumor mimicking a hydatid cyst of the lung in children: case report.
AB  - Askin tumor is a malignant small round cell tumor that originates from the
      thoracopulmonary region, usually observed in young subjects. We report a case of
      askin tumor in a 11 year-old men, who had in his past history a surgery for
      hydatid cyst of the liver, actually hospitalised for right pulmonary upper lobe
      mass of the lung. After resection of the mass, the pathological exam confirmed
      the diagnosis of primitive neuroectodermal tumor (PNET). An adjuvant treatment
      (radiotherapy and chemotherapy) was done; the patient died 11 months after
      surgery. Askin tumor is an exclusion diagnosis not always readily made. 

PMID- 25374637
TI  - [Coloboma of the upper eyelid].

PMID- 25374639
TI  - [Paraneoplastic cutaneous vasculitis revealing non-Hodgkin's lymphoma].

PMID- 25374638
TI  - The epidemiology of lymphatic filariasis in Ghana, explained by the possible
      existence of two strains of Wuchereria bancrofti.
AB  - INTRODUCTION: Lymphatic filariasis is a debilitating disease caused by the
      filarial worm Wuchereria bancrofti. It is earmarked for elimination by the year
      2020 through the Global Program for the Elimination of LF (GPELF). In Ghana, mass
      treatment has been on-going since the year 2000. Earlier studies have revealed
      differing epidemiology of LF in the North and South of Ghana. This study was
      therefore aimed at understanding the possible impacts of W. bancrofti diversity
      on the epidemiology and control of LF in Ghana. METHODS: The Mitochondrial,
      Cytochrome C Oxidase I gene of W. bancrofti samples was sequenced and analyzed.
      The test sequences were grouped into infrapopulations, and pairwise differences
      (pi) and mutation rates (theta) were computed. The amount of variance within and
      among populations was also computed using the AMOVA. The evolutionary history was
      inferred using the Maximum Parsimony method. RESULTS: Seven samples from the
      South and 15 samples from the North were sequenced, and submitted to GenBank with
      accession numbers GQ479497- GQ479518. The results revealed higher mutation
      frequencies in the southern population, compared to the northern population.
      Haplotype analyses revealed a total of 11 haplotypes (Hap) in all the 22 DNA
      sequences, with high genetic variation and polymorphisms within the southern
      samples. CONCLUSION: This study showed that there is considerable genetic
      variability within W. bancrofti populations in Ghana, differences that might
      explain the observed epidemiology of LF. Further studies are however required for
      an in-depth understanding of LF epidemiology and control.

PMID- 25374640
TI  - Spontaneous dislocation of a crystalline lens to the anterior chamber with
      pupillary block glaucoma in Noonan Syndrome: a case report.
AB  - We report a 13-year-old child with Noonan Syndrome who developed spontaneous
      dislocation of the crystalline lens in anterior chamber leading to pupillary
      block glaucoma in the left eye and subluxation of lens in right eye.
      Intracapsular extraction of the dislocated lens was done in the left eye. Prompt
      diagnosis and management is needed in such cases to avoid glaucoma and corneal
      endothelial cell damage. We could not find any such case after thorough Medline
      search. 

PMID- 25374641
TI  - Eales disease: no typical clinical presentation.

PMID- 25374642
TI  - [Acute intussusception on jejunostomy tube: a rare cause of intestinal
      obstruction].

PMID- 25374643
TI  - [Fractures of the radial head in children: about 66 cases].

PMID- 25374644
TI  - [When ankle sprain hides a dislocation of peroneal tendons].

PMID- 25374645
TI  - Dural ectasia of the optic nerve sheath.
AB  - Optic nerve dural ectasia is a rare cause of optic nerve sheath enlargement due
      to the accumulation of CSF around the optic nerve with no associated pathology.
      It diagnosed by MRI studies and can follow benign or sometimes an unfavorable
      course. We describe the case of a 24-day-old female referred for a visual
      blurring, which we diagnosed as a dural ectasia of the optic nerve sheath by MRI
      and confirmed in surgical intervention. We present this case report to illustrate
      the classic imaging features of the disease. 

PMID- 25374646
TI  - [Bilateral retinoblastoma: report of a case].

PMID- 25374647
TI  - Mobile "doctors" and their medical diagnosis in rural Southern Nigeria. Truth or
      deception? A public health case report.
AB  - Mobile "doctors" are traditional herbal medical practitioners who move from one
      rural community in Nigeria to another diagnosing disease using a digital
      thermometer and stethoscope before selling their herbal drugs to the patients.
      Are their diagnosis correct or just a deception? This reports looks at three
      cases of mobile doctors ' diagnosis of patients in rural southern Nigeria. 

PMID- 25374648
TI  - The prevalence of chlamydia trachomatis among patients with acute conjunctivitis
      in Kasr Alainy ophthalmology clinic.
AB  - INTRODUCTION: Trachoma is a leading cause of avoidable blindness and endemic
      conjunctivitis in 57 countries. It infects approximately 84 million people
      globally, and continues to threaten over 10% of the world's population with the
      risk of blindness. METHODS: This is a cross sectional descriptive study assessing
      patients presenting with acute conjunctivitis. A full history was taken from
      patients followed by examination of both eyes. A conjunctival swab was taken and
      a sample of tears was collected and handled at the central laboratory unit at
      Kasr AlAiny hospital for culture and sensitivity of the swab and ELISA for tears
      searching for Immunoglobulin G and Immunoglobulin M of chlamydia trachomatis.
      RESULTS: The prevalence of bacterial conjunctivitis encounted for 45.7% and non
      bacterial 54.3% of the studied group. The anti-chlamydial antibodies were
      positive in the tears of 31.1% of patients. While the other bacterial organisms
      responsible for 14.6%. CONCLUSION: The study concluded that trachoma accounts for
      one third of the cases of acute conjunctivitis while the other bacterial
      organisms responsible for about 14.6%. More than half of the cases have other
      causes as viral, allergic, mechanical or chemical induced conjunctivitis.

PMID- 25374649
TI  - [Dosage of 25-OH vitamin D: experience of central clinical biochemistry
      laboratory of Ibn Sina Hospital].

PMID- 25374650
TI  - Ghrelin therapy improves survival after whole-body ionizing irradiation or
      combined with burn or wound: amelioration of leukocytopenia, thrombocytopenia,
      splenomegaly, and bone marrow injury.
AB  - Exposure to ionizing radiation alone (RI) or combined with traumatic tissue
      injury (CI) is a crucial life-threatening factor in nuclear and radiological
      events. In our laboratory, mice exposed to (60)Co-gamma-photon radiation (9.5 Gy,
      0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W
      CI) or burns (R-B CI) experienced an increment of >=18% higher mortality over a
      30-day observation period compared to RI alone. CI was accompanied by severe
      leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after
      injury, numbers of WBC and platelets still remained very low in surviving RI and
      CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered
      towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted
      in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating
      peptide) therapy increased survival, mitigated body-weight loss, accelerated
      wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy
      increased survival and numbers of neutrophils, lymphocytes, and platelets and
      ameliorated bone-marrow cell depletion. In RI mice, this treatment increased
      survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel
      results are the first to suggest that ghrelin therapy effectively improved
      survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone
      marrow injury or the RI-induced decreased hemoglobin and hematocrit.

PMID- 25374651
TI  - A quantitative method to monitor reactive oxygen species production by electron
      paramagnetic resonance in physiological and pathological conditions.
AB  - The growing interest in the role of Reactive Oxygen Species (ROS) and in the
      assessment of oxidative stress in health and disease clashes with the lack of
      consensus on reliable quantitative noninvasive methods applicable. The study
      aimed at demonstrating that a recently developed Electron Paramagnetic Resonance
      microinvasive method provides direct evidence of the "instantaneous" presence of
      ROS returning absolute concentration levels that correlate with "a posteriori"
      assays of ROS-induced damage by means of biomarkers. The reliability of the
      choice to measure ROS production rate in human capillary blood rather than in
      plasma was tested (step I). A significant (P < 0.01) linear relationship between
      EPR data collected on capillary blood versus venous blood (R (2) = 0.95), plasma
      (R (2) = 0.82), and erythrocytes (R (2) = 0.73) was found. Then (step II) ROS
      production changes of various subjects' categories, young versus old and healthy
      versus pathological at rest condition, were found significantly different (range
      0.0001-0.05 P level). The comparison of the results with antioxidant capacity and
      oxidative damage biomarkers concentrations showed that all changes indicating
      increased oxidative stress are directly related to ROS production increase.
      Therefore, the adopted method may be an automated technique for a lot of routine
      in clinical trials.

PMID- 25374652
TI  - Fatigue, Mood, and Sleep, During Intraperitoneal Chemotherapy: A Pilot Case
      Control Study.
AB  - The goal of this pilot study was to compare longitudinal changes in fatigue,
      depressive symptoms, sleep, and activity in women (n = 10) undergoing
      intraperitoneal (IP) versus intravenous (IV) chemotherapy for ovarian cancer.
      Fatigue and depressive symptoms were assessed via self -report and sleep and
      activity via wrist actigraphy in the week before and the week after the first
      infusion. Both groups demonstrated increases in fatigue and depressive symptoms,
      declines in sleep, reduced daytime activity, and decreased rhythmicity of
      sleep/activity patterns (p<.05). Effect sizes for within-group comparisons tended
      to be higher in the IP group (ds = -.15 to -8.03) than the IV group (ds = .12 to
      1.40). Between-group comparisons revealed that IP patients demonstrated trends
      towards more severe symptoms post-chemotherapy in nearly all outcomes (p<.10).
      These results suggest that IP patients experience large increases in fatigue,
      depressive symptoms, and alterations in sleep and activity relative to IV
      patients.

PMID- 25374653
TI  - Editorial.

PMID- 25374654
TI  - 'Fertility Awareness-Based Methods' and subfertility: a systematic review.
AB  - Fertility awareness based methods (FABMs) can be used to ameliorate the
      likelihood to conceive. A literature search was performed to evaluate the
      relationship of cervical mucus monitoring (CMM) and the day-specific -pregnancy
      rate, in case of subfertility. A MEDLINE search revealed a total of 3331
      articles. After excluding articles based on their relevance, 10 studies and were
      selected. The observed studies demonstrated that the cervical mucus monitoring
      (CMM) can identify the days with the highest pregnancy rate. According to the
      literature, the quality of the vaginal discharge correlates well with the cycle
      specific probability of pregnancy in normally fertile couples but less in
      subfertile couples. The results indicate an urgent need for more prospective
      randomised trials and -prospective cohort studies on CMM in a subfertile
      population to evaluate the effectiveness of CMM in the subfertile couple. 

PMID- 25374655
TI  - Issues arising when crossing a border to give birth: an exploratory study on the
      French-Belgian border.
AB  - BACKGROUND: Anecdotal evidence suggests that many organised initiatives for cross
      border collaboration in healthcare in border regions originate from the need for
      women to give birth close to home. Despite this, there is remarkably little
      research on these practices and the specific modes of collaboration between
      providers and experiences and needs of these women. In this paper we describe the
      experiences of French women who choose to give birth in Belgium. STUDY DESIGN: We
      conducted semi-structured interviews with 14 key informants and captured the
      experiences of 14 French mothers using a 40-item questionnaire. RESULTS: The
      chief motivations for French mothers to cross the border to deliver a baby in
      Belgium were geographical proximity as well as perceived better quality of care.
      Several procedural differences between France and Belgium were highlighted as
      possibly affecting the quality of follow-up care, including the absence, in some
      cases, of a contact person in France, and communication problems between
      providers. CONCLUSION: There is a tension between the testimony of patients who
      are clearly satisfied and evidence of problems in communication and weak
      collaboration between providers on either side of this cross border
      collaboration. This paradox requires more research efforts to generate clear
      evidence of the added value of these cross-border collaborations for patients.

PMID- 25374656
TI  - Strategies to optimize the performance of Robotic-assisted laparoscopic
      hysterectomy.
AB  - A hybrid technique of robot-assisted, laparoscopic hysterectomy using the
      ENSEAL((r)) Tissue Sealing Device is described in a retrospective, consecutive,
      observational case series. Over a 45 month period, 590 robot-assisted total
      laparoscopic hysterectomies +/- oophorectomy for benign and malignant indications
      were performed by a single surgeon with a bedside assistant at a tertiary
      healthcare center. Patient demographics, indications for surgery, comorbidities,
      primary and secondary surgical procedures, total operative and surgical time,
      estimated blood loss (EBL), length of stay (LOS), complications, transfusions and
      subsequent readmissions were analyzed. The overall complication rate was 5.9%
      with 35 patients experiencing 69 complications. Mean (SD) surgery time, operating
      room (OR) time, EBL, and LOS for the entire cohort were 75.5 (39.42) minutes,
      123.8 (41.15) minutes, 83.1 (71.29) millilitres, and 1.2 (0.93) days,
      respectively. Mean surgery time in the first year (2009) was 91.6 minutes, which
      declined significantly each year by 18.0, 19.0, and 24.3 minutes, respectively.
      EBL and LOS did not vary -significantly across the entire series. Using the
      cumulative sum method, an optimization curve for surgery time was evaluated, with
      three distinct optimization phases observed. In summary, the use of an advanced
      laparoscopic tissue-sealing device by a bedside surgical assistant provided an
      improved operative efficiency and reliable vessel sealing during robotic
      hysterectomy. 

PMID- 25374657
TI  - Cumulative live birth rate and assisted reproduction: impact of female age and
      transfer day.
AB  - BACKGROUND: Many studies on assisted reproductive technology examine live birth
      rate per cycle. However, after a cycle fails, couples often want to know what
      their chances are of having a live birth if they continue treatment. From a
      patients' perspective, the cumulative probability of live birth is more
      informative. MATERIALS AND METHODS: This study includes patients who underwent
      fresh, frozen and non-donor ICSI cycles at our IVF unit between 2006-2012.
      Patients were divided into two groups; Group 1 represented those who underwent
      only Day 5 transfers, Group 2 represented only Day 3 transfers. Patients who
      underwent both were excluded. -Cycles were analyzed until the first live birth or
      the end of the 3rd cycle. Using Kaplan-Meier analysis, we estimated the
      cumulative live birth rates for each group and according to female age. RESULTS:
      The mean age for Group 1 was significantly lower than for Group 2. After 3
      cycles, Group 1's CLBR was 79% versus 66% in Group 2. When analyzing the live
      births by age and group, there was a significant difference in the CLBR after 3
      cycles with the women less than 35 years having the highest CLBR and the women 40
      years or older having the lowest CLBR. CONCLUSION: In women less than 35 years,
      excellent CLBR can be achieved irrespective of the transfer day. For women 40
      years and above, better results of CLBR are observed with Day 5 transfers. Our
      findings may impact the counseling of couples considering IVF treatment.

PMID- 25374658
TI  - The potential of letrozole use for priming in vitro maturation cycles.
AB  - OBJECTIVE: To compare the pregnancy rates with two different methods of priming
      for in vitro maturation cycles (IVM). Cycles using letrozole together with hCG
      were compared to cycles using FSH together with hCG in 75 cycles in patients
      being treated for infertility by IVM. STUDY DESIGN: Retrospective cohort non
      inferiority trial Results: Using letrozole for priming was found to not be
      inferior to using FSH for priming cycles. The live birth rate per transfer was
      31.6% in letrozole primed cycles compared to 20.8% in FSH primed cycles (not
      significant). However, FSH priming produced more oocytes that were mature on the
      day of retrieval (p = 0.004) and also resulted in more high quality embryos than
      did letrozole priming (p = 0.004). CONCLUSION: Letrozole may be used for priming
      in IVM cycles in which the clinician views the characteristics of letrozole as
      more desirable than FSH.

PMID- 25374659
TI  - A new approach for ovarian stimulation in IVF using Corifollitropin Alfa in
      combination with GnRH analogues to trigger final oocyte maturation. A pilot
      study.
AB  - A pilot study of 10 patients undergoing IVF stimulation, using the new
      combination of Corifollitropin Alfa with highly purified hMG and GnRH antagonists
      has been performed, whereas final oocyte maturation was induced by GnRH
      analogues. The hormonal profiles were analyzed, as well as the clinical outcome.
      All patients were recruited between March 1st 2013 and June 30(th) 2013. They
      were all younger than 38 years, had a normal BMI (between 18,0 and 32,0) and did
      not have more than three previous IVF stimulations. The combination of long
      acting FSH with hphMG, and under protection of GnRH antagonists against
      spontaneous LH-surge, provided a normal hormonal profile for estradiol,
      progesterone, LH, and FSH. The average oocyte quality and embryo quality were
      excellent, which resulted in four pregnancies out of ten. We conclude that the
      described combination is a safe, efficient, and patient friendly alternative for
      the classical IVF stimulation. 

PMID- 25374660
TI  - Pregnancy, postpartum and the thyroid: isn't it time to offer women optimal care?
AB  - In 2011, the American Thyroid association published guidelines concerning the
      attitude toward maternal thyroid (dys)function during pregnancy and postpartum.
      The American Association of Clinical Endocrinologists also -recommend a case
      finding approach although several studies has shown that up to 50% of women with
      thyroid dysfunction will be missed. Recently, it was shown that 0.6% of all
      pregnant women suffer from unknown overt hypothyroidism as a consequence of not
      screening: annually 1000 women in the Netherlands, 6000 in UK and over 24.000 in
      the US. Cost-effective studies have shown that screening of all pregnant women is
      beneficial. This commentary criticizes the guidelines that (incorrectly) use RCT
      principles rather than following the more modern concepts of preventive medicine.
      Assessing a risk profile for an endocrine syndrome does not necessarily mean
      intervention per se. Informing women that they are at great risk for developing
      future thyroid dysfunction might help to reduce the tremendous patient and doctor
      delay of diagnosing hypothyroidism in pregnancy. 

PMID- 25374661
TI  - GWATCH: a web platform for automated gene association discovery analysis.
AB  - BACKGROUND: As genome-wide sequence analyses for complex human disease
      determinants are expanding, it is increasingly necessary to develop strategies to
      promote discovery and validation of potential disease-gene associations.
      FINDINGS: Here we present a dynamic web-based platform - GWATCH - that automates
      and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene
      association search and discovery analysis of large genome-wide datasets; 2)
      Expanded visual display of gene associations for genome-wide variants (SNPs,
      indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region,
      and a dynamic genome browser illustrating gene association chromosomal regions;
      3) Real-time validation/replication of candidate or putative genes suggested from
      other sources, limiting Bonferroni genome-wide association study (GWAS)
      penalties; 4) Open data release and sharing by eliminating privacy constraints
      (The National Human Genome Research Institute (NHGRI) Institutional Review Board
      (IRB), informed consent, The Health Insurance Portability and Accountability Act
      (HIPAA) of 1996 etc.) on unabridged results, which allows for open access
      comparative and meta-analysis. CONCLUSIONS: GWATCH is suitable for both GWAS and
      whole genome sequence association datasets. We illustrate the utility of GWATCH
      with three large genome-wide association studies for HIV-AIDS resistance genes
      screened in large multicenter cohorts; however, association datasets from any
      study can be uploaded and analyzed by GWATCH.

PMID- 25374662
TI  - iReport: a generalised Galaxy solution for integrated experimental reporting.
AB  - BACKGROUND: Galaxy offers a number of visualisation options with components, such
      as Trackster, Circster and Galaxy Charts, but currently lacks the ability to
      easily combine outputs from different tools into a single view or report. A
      number of tools produce HTML reports as output in order to combine the various
      output files from a single tool; however, this requires programming and knowledge
      of HTML, and the reports must be custom-made for each new tool. FINDINGS: We have
      developed a generic and flexible reporting tool for Galaxy, iReport, that allows
      users to create interactive HTML reports directly from the Galaxy UI, with the
      ability to combine an arbitrary number of outputs from any number of different
      tools. Content can be organised into different tabs, and interactivity can be
      added to components. To demonstrate the capability of iReport we provide two
      publically available examples, the first is an iReport explaining about iReports,
      created for, and using content from the recent Galaxy Community Conference 2014.
      The second is a genetic report based on a trio analysis to determine candidate
      pathogenic variants which uses our previously developed Galaxy toolset for whole
      genome NGS analysis, CGtag. These reports may be adapted for outputs from any
      sequencing platform and any results, such as omics data, non-high throughput
      results and clinical variables. CONCLUSIONS: iReport provides a secure,
      collaborative, and flexible web-based reporting system that is compatible with
      Galaxy (and non-Galaxy) generated content. We demonstrate its value with a real
      life example of reporting genetic trio-analysis.

PMID- 25374663
TI  - Regulating dynamin dynamics during endocytosis.
AB  - Dynamin is a large GTPase that mediates plasma membrane fission during clathrin
      mediated endocytosis. Dynamin assembles into polymers on the necks of budding
      membranes in cells and has been shown to undergo GTP-dependent conformational
      changes that lead to membrane fission in vitro. Recent efforts have shed new
      light on the mechanisms of dynamin-mediated fission, yet exactly how dynamin
      performs this function in vivo is still not fully understood. Dynamin interacts
      with a number of proteins during the endocytic process. These interactions are
      mediated by the C-terminal proline-rich domain (PRD) of dynamin binding to SH3
      domain-containing proteins. Three of these dynamin-binding partners (intersectin,
      amphiphysin and endophilin) have been shown to play important roles in the
      clathrin-mediated endocytosis process. They promote dynamin-mediated plasma
      membrane fission by regulating three important sequential steps in the process:
      recruitment of dynamin to sites of endocytosis; assembly of dynamin into a
      functional fission complex at the necks of clathrin-coated pits (CCPs); and
      regulation of dynamin-stimulated GTPase activity, a key requirement for fission. 

PMID- 25374664
TI  - Reaching a consensus on the mechanism of dynamin?
AB  - AMONG THE PROTEINS INVOLVED IN LIPID MEMBRANE REMODELING IN INTRACELLULAR
      TRAFFIC, DYNAMIN HAS BEEN THE FOCUS OF MANY STUDIES, AS IT WAS THE FIRST PROTEIN
      SHOWN TO BE MECHANISTICALLY INVOLVED IN MEMBRANE FISSION: the reaction by which a
      vesicle neck can be severed to release a free vesicle. After almost 25 years of
      research, a wide variety of data from various techniques has been acquired on the
      mechanism by which dynamin breaks membranes. However, the literature may
      sometimes sound confusing, and the primary goal of this review will be to provide
      a stepping stone towards a potential consensus on how dynamin may work. I will
      then discuss the most recent findings in light of previous work, and the future
      possible lines of research in the field of dynamin. 

PMID- 25374665
TI  - Natural killer cell regulation - beyond the receptors.
AB  - Natural killer (NK) cells are lymphocytes that are important for early and
      effective immune responses against infections and cancer. In the last 40 years,
      many receptors, their corresponding ligands and signaling pathways that regulate
      NK cell functions have been identified. However, we now know that additional
      processes, such as NK cell education, differentiation and also the formation of
      NK cell memory, have a great impact on the reactivity of these cells. Here, we
      summarize the current knowledge about these modulatory processes. 

PMID- 25374666
TI  - Control systems and coordination protocols of the secretory pathway.
AB  - Like other cellular modules, the secretory pathway and the Golgi complex are
      likely to be supervised by control systems that support homeostasis and optimal
      functionality under all conditions, including external and internal
      perturbations. Moreover, the secretory apparatus must be functionally connected
      with other cellular modules, such as energy metabolism and protein degradation,
      via specific rules of interaction, or "coordination protocols". These regulatory
      devices are of fundamental importance for optimal function; however, they are
      generally "hidden" at steady state. The molecular components and the architecture
      of the control systems and coordination protocols of the secretory pathway are
      beginning to emerge through studies based on the use of controlled transport
      specific perturbations aimed specifically at the detection and analysis of these
      internal regulatory devices. 

PMID- 25374667
TI  - Advances in the diagnosis and treatment of sarcoidosis.
AB  - This manuscript outlines recent advances in the diagnosis and treatment of
      sarcoidosis. The diagnosis of sarcoidosis can occasionally be made on clinical
      grounds without a confirmatory biopsy when very specific clinical findings are
      present. Otherwise, the diagnosis requires histologic evidence of granulomatous
      inflammation, exclusion of alternative causes, and evidence of systemic disease.
      Because there is no available diagnostic test for sarcoidosis, the diagnosis is
      never completely secure. Instruments have been developed to establish the
      presence of sarcoidosis in a second organ and hence establish the systemic nature
      of the disease. Corticosteroids remain the drug of choice for the treatment of
      sarcoidosis. Additional sarcoidosis medications are most commonly used as
      corticosteroid-sparing agents. Recent clinical sarcoidosis drug trials have
      exposed important issues that may confound trial results, including selecting
      patients with active disease, identifying study drug effects in patients
      receiving concomitant corticosteroids, and establishing proper study endpoints. 

PMID- 25374668
TI  - Rethinking cardiac metabolism: metabolic cycles to refuel and rebuild the failing
      heart.
AB  - The heart is a self-renewing biological pump that converts chemical energy into
      mechanical energy. The entire process of energy conversion is subject to complex
      regulation at the transcriptional, translational and post-translational levels.
      Within this system, energy transfer occurs with high efficiency, facilitated by a
      series of compound-conserved cycles. At the same time, the constituent myocardial
      proteins themselves are continuously made and degraded in order to adjust to
      changes in energy demand and changes in the extracellular environment. We
      recently have identified signals arising from intermediary metabolism that
      regulate the cycle of myocardial protein turnover. Using a new conceptual
      framework, we discuss the principle of metabolic cycles and their importance for
      refueling and for rebuilding the failing heart. 

PMID- 25374669
TI  - Mechanical circulatory support in acute cardiogenic shock.
AB  - Cardiogenic shock complicates about 5% to 8% of all admissions for acute
      myocardial infarction, and despite advancement in treatment over the past 50
      years, mortality remains unacceptably high. Management with vasoactive agents
      after revascularization can have its limitations and thus mechanical circulatory
      support is often initiated. Intra-aortic balloon pumps (IABPs) are the devices
      most commonly used worldwide. IABPs appeared to improve mortality when used along
      with fibrinolytic therapy but may not when used along with percutaneous coronary
      interventions. Extracorporeal membrane oxygenation (ECMO) is utilized in the
      setting of worsening tissue perfusion despite inotropes and IABP utilization.
      Although retrospective studies show some mortality benefit, randomized
      prospective studies have not yet demonstrated ECMO to be advantageous either with
      or without IABP. Percutaneous left ventricular assist devices such as
      TandemHeart(r) and Impella are easier to institute than ECMO and are better for
      hemodynamics compared with the IABP but also have not yet shown a mortality
      benefit. More randomized studies are needed to define the most appropriate role
      of the various mechanical support devices in cardiogenic shock. 

PMID- 25374670
TI  - Transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation was developed to offer a therapeutic
      solution to patients with severe symptomatic aortic stenosis who are not
      candidates for conventional aortic valve replacement. The improvement in
      transcatheter aortic valve implantation outcomes is still of concern in the areas
      of stroke, vascular injury, heart block, paravalvular regurgitation and valve
      durability. Concomitantly, the progress, both technical and in terms of material
      advances of transcatheter valve systems, as well as in patient selection, renders
      transcatheter aortic valve implantation an increasingly viable treatment for more
      and more patients with structural heart disease. 

PMID- 25374671
TI  - Expanding use of new oral anticoagulants.
AB  - New, non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to
      overcome the limitations of warfarin. These include dabigatran, which inhibits
      thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In
      the US, rivaroxaban and apixaban are licensed for thromboprophylaxis after
      elective hip or knee arthroplasty, and rivaroxaban and dabigatran are approved
      for treatment of venous thromboembolism. Dabigatran, rivaroxaban, and apixaban
      also are licensed for stroke prevention in eligible patients with atrial
      fibrillation. Designed to be given in fixed doses without routine coagulation
      monitoring, the NOACs are more convenient to administer than warfarin. Phase III
      clinical trials have shown that the NOACs are at least as effective as warfarin
      and are associated with less intracranial bleeding. This article compares the
      pharmacological properties of the NOACs with those of warfarin, describes the
      clinical trial data with the NOACs in the approved indications, outlines the
      unmet medical needs that the NOACs address, highlights the potential limitations
      of the NOACs, and provides guidance on the optimal use of the NOACs. 

PMID- 25374672
TI  - Management of allergic rhinitis.
AB  - In this paper, we review the current management of allergic rhinitis and new
      directions for future treatment. Currently, management includes pharmacotherapy,
      allergen avoidance and possibly immunotherapy. The simple washing of nasal
      cavities using isotonic saline provides a significant improvement and is useful,
      particularly in children. The most effective medication in persistent rhinitis
      used singly is topical corticosteroid, which decreases all symptoms, including
      ocular ones. Antihistamines reduce nasal itch, sneeze and rhinorrhea and can be
      used orally or topically. When intranasal antihistamine is used together with
      topical corticosteroid, the combination is more effective and acts more rapidly
      than either drug used alone. Alternative therapies, such as homeopathy,
      acupuncture and intranasal carbon dioxide, or devices such nasal air filters or
      intranasal cellulose, have produced some positive results in small trials but are
      not recommended by Allergic Rhinitis and its Impact on Asthma (ARIA). In the
      field of allergic immunotherapy, subcutaneous and sublingual routes are currently
      used, the former being perhaps more efficient and the latter safer. Sublingual
      tablets are now available. Their efficacy compared to standard routes needs to be
      evaluated. Efforts have been made to develop more effective and simpler
      immunotherapy by modifying allergens and developing alternative routes. Standard
      allergen avoidance procedures used alone do not provide positive results. A
      comprehensive, multi-trigger, multi-component approach is needed, including
      avoidance of pollutants such as cigarette smoke. 

PMID- 25374674
TI  - Advances in treating acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) arises within the bone marrow from a malignant
      hematopoietic progenitor cell. Though AML is still often fatal, cure rates
      overall continue to improve incrementally yet steadily, primarily for two
      reasons: first, insights into the pathogenesis of AML over the last several
      decades have led to the development of a relatively sophisticated classification
      scheme that allows more nuanced risk stratification to guide treatment choices;
      second, improvements in stem cell transplantation have allowed many more patients
      to take advantage of this highly effective therapeutic technique. Improvements in
      overall survival for patients with AML are expected to continue rising because of
      the anticipated introduction of targeted therapies into this treatment platform. 

PMID- 25374676
TI  - Preconditioning serum levels of endothelial cell-derived molecules and the risk
      of posttransplant complications in patients treated with allogeneic stem cell
      transplantation.
AB  - Endothelial cells are involved in the pathogenesis of acute graft-versus-host
      disease (GVHD) after allogeneic stem cell transplantation. These cells express
      several molecules that can be detected as biologically active soluble forms;
      serum levels of these molecules may thereby reflect the functional status of
      endothelial cells. Furthermore, acute GVHD is an inflammatory reaction and
      endothelial cells function as local regulators of inflammation. We therefore
      investigated whether differences in preconditioning/pretransplant serum levels of
      endothelium-expressed molecules (i.e., endocan, vascular cell adhesion molecule 1
      (VCAM-1), and E-selectin) were associated with a risk of posttransplant GVHD. Our
      study should be regarded as a population-based study of consecutive and thereby
      unselected patients (n = 56). Analysis of this pretreatment endothelium biomarker
      profile by unsupervised hierarchical clustering identified a subset of patients
      with increased early nonrelapse mortality. Furthermore, low endocan levels were
      significantly associated with acute GVHD in the liver and gastrointestinal tract,
      whereas high VCAM-1 levels were associated with acute GVHD in the skin only. Our
      study suggests that the preconditioning/pretransplant status of endothelial cells
      (possibly through altered trafficking of immunocompetent cells) is important for
      the risk and the organ involvement of later acute GVHD. 

PMID- 25374673
TI  - Future therapy of portal hypertension in liver cirrhosis - a guess.
AB  - In patients with chronic liver disease, portal hypertension is driven by
      progressive fibrosis and intrahepatic vasoconstriction. Interruption of the
      initiating and perpetuating etiology-mostly leading to necroinflammation-is
      possible for several underlying causes, such as autoimmune hepatitis, hepatitis B
      virus (HBV) infection, and most recently hepatitis C virus (HCV) infection. Thus,
      in the long run, lifestyle-related liver damage due to chronic alcoholism or
      morbid obesity will remain the main factor leading to portal hypertension. Both
      causes are probably more easily countered by socioeconomic measures than by
      individual approaches. If chronic liver injury supporting fibrogenesis and portal
      hypertension cannot be interrupted, a wide variety of tools are available to
      modulate and reduce intrahepatic resistance and therewith portal hypertension.
      Many of these have been evaluated in animal models. Also, some well-established
      drugs, which are used in humans for other indications (for example, statins), are
      promising if applied early and concomitantly to standard therapy. In the future,
      more individually tailored strategies must also be considered in line with the
      spectrum of portal hypertensive complications and risk factors defined by high
      throughput analysis of the patient's genome, transcriptome, metabolome, or
      microbiome. 

PMID- 25374677
TI  - Association between anxiety levels and weight change in the multiethnic study of
      atherosclerosis.
AB  - OBJECTIVE: To examine the association between anxiety and weight change in a
      multiethnic cohort followed for approximately 10 years. METHODS: The study
      population consisted of participants of the multiethnic study of atherosclerosis
      who met specified inclusion criteria (n = 5,799). Weight was measured at baseline
      and four subsequent follow-up exams. Anxiety was analyzed as sex-specific anxiety
      quartiles (QANX). The relationship between anxiety level and weight change was
      examined using a mixed-effect model with weight as the dependent variable,
      anxiety and time as the independent variables, and adjusted for covariates.
      RESULTS: Average annual weight change (range) was -0.17 kg (-6.04 to 4.38 kg) for
      QANX 1 (lowest anxiety), -0.16 kg (-10.71 to 4.45 kg) for QANX 2, -0.15 kg (-8.69
      to 6.39 kg) for QANX 3, and -0.20 kg (-7.12 to 3.95 kg) for QANX 4 (highest
      anxiety). No significant association was noted between QANX and weight change.
      However, the highest QANX was associated with a -2.48 kg (95% CI = -3.65, -1.31)
      lower baseline weight compared to the lowest QANX after adjustment for all
      covariates. CONCLUSIONS: Among adults, age 45-84, higher levels of anxiety,
      defined by the STPI trait anxiety scale, are associated with lower average
      baseline weight but not with weight change.

PMID- 25374678
TI  - Venous Thromboembolism following Elective Aesthetic Plastic Surgery: A
      Longitudinal Prospective Study in 1254 Patients.
AB  - Background. Venous thromboembolism (VTE) is a disorder with short-term mortality
      and long-term morbidity. Healthy patients submitted to elective aesthetic plastic
      surgeries (EAPS) have risk factors to develop VTE not well established yet. The
      objective of this study was to examine the incidence and risk factors for VTE in
      these patients. Methods. Longitudinal, prospective (minimum follow-up of 3
      months), observational study. Comprehensive information on patient
      characteristics and surgeries performed was obtained. Preoperative,
      intraoperative, and postoperative risk factors were analyzed for their
      association with VTE. Results. A total of 1254 patients were included in the
      study. Postoperative VTE occurred in 17 (1,35%) of patients. VTE was more
      frequent in patients more than 40 years old (82.3%). Smoking, patients with 2 or
      3 pregnancies, and hormone replacement therapy, and oral contraceptives use
      presents higher levels of VTE. In this study we have not found any correlation
      between liposuction, augmentation mammoplasty, mastopexy, and rhinoplasty as an
      isolated risk factor for VTE. Conclusions. The incidence of VTE in patients
      undergoing EAPS was 1.35%. Patients with more than 40 years of age, tobacco
      users, patients with 2 or more pregnancies, and hormone replacement therapy or
      oral contraceptives use presents higher levels of VTE. 

PMID- 25374679
TI  - Photovoice: a novel approach to improving antituberculosis treatment adherence in
      pune, India.
AB  - We compared antituberculosis treatment (ATT) adherence and outcomes among
      patients exposed to Photovoice (video of previously cured TB patients sharing
      experiences about TB treatment) versus those not exposed. The odds of successful
      outcome (i.e., cured or completing treatment) for the 135 patients who watched
      Photovoice were 3 times greater (odds ratio: 2.8; 95% CI: 1.3-6.1) than for
      patients who did not watch Photovoice. The comparison group, on average, missed
      more doses (10.9 doses; 95% CI: 6.6-11.1) than the intervention group who saw
      Photovoice (5.5 doses; 95% CI: 3.7-6.1). Using Photovoice at initiation of ATT
      has the potential to improve treatment adherence and outcomes. 

PMID- 25374680
TI  - Whole prostate volume and shape changes with the use of an inflatable and
      flexible endorectal coil.
AB  - Purpose. To determine to what extent an inflatable endorectal coil (ERC) affects
      whole prostate (WP) volume and shape during prostate MRI. Materials and Methods.
      79 consecutive patients underwent T2W MRI at 3T first with a 6-channel surface
      coil and then with the combination of a 16-channel surface coil and ERC in the
      same imaging session. WP volume was assessed by manually contouring the prostate
      in each T2W axial slice. PSA density was also calculated. The maximum anterior
      posterior (AP), left-right (LR), and craniocaudal (CC) prostate dimensions were
      measured. Changes in WP prostate volume, PSA density, and prostate dimensions
      were then evaluated. Results. In 79 patients, use of an ERC yielded no
      significant change in whole prostate volume (0.6 +/- 5.7%, P = 0.270) and PSA
      density (-0.2 +/- 5.6%, P = 0.768). However, use of an ERC significantly
      decreased the AP dimension of the prostate by -8.6 +/- 7.8% (P < 0.001),
      increased LR dimension by 4.5 +/- 5.8% (P < 0.001), and increased the CC
      dimension by 8.8 +/- 6.9% (P < 0.001). Conclusion. Use of an ERC in prostate MRI
      results in the shape deformation of the prostate gland with no significant change
      in the volume of the prostate measured on T2W MRI. Therefore, WP volumes
      calculated on ERC MRI can be reliably used in clinical workflow. 

PMID- 25374681
TI  - Syntheses and biological activity of some derivatives of C-9154 antibiotic.
AB  - This research was undertaken to design several new antibiotics, by structurally
      modifying the C-9154 antibiotic, simultaneously improving its activity and
      lowering toxicity. This was achieved by synthesizing an analogue to the C-9154
      antibiotic and seven derivatives of this analogue. The approach was to
      significantly reduce the polarity of the synthesized analogue in the derivatives
      to achieve increased permeability across cell membranes by conversion of the
      highly polar carboxylic group to an ester functional group. The compounds were
      fully characterized using infrared, GC-MS, and 1D and 2D NMR experiments. The in
      vitro biological activity of the compounds showed that the derivatives were more
      active than the analogue as was anticipated and both were more active than the
      standard drugs used for comparison. Work is ongoing to establish applications for
      the compounds as antiplasmodials, antivirals, anticancers/tumours,
      antitrypanosomiasis, anthelminthic, and as general antibiotics for human,
      veterinary, and even agricultural use as they had marked effect on both Gram
      positive and Gram-negative bacteria and some fungi. 

PMID- 25374682
TI  - Comparative Analysis of the Antioxidant Activity of Cassia fistula Extracts.
AB  - Antioxidant potential of various extracts of Cassia fistula was determined by the
      DPPH, FRAP, Fe(3+) reducing power, and hydrogen peroxide scavenging assay.
      Methanolic extracts of Cassia fistula showed the highest amount of phenolic and
      flavonoid content and reducing capacity, whereas hexane extracts exhibited the
      lowest level of reducing capacity. The order of antioxidant activity in Cassia
      fistula extracts displayed from higher to lower level as methanolic extracts of
      pulp, methanolic extracts of seed, hexane extracts of pulp, and hexane extracts
      of seed. The antioxidant potential of Cassia fistula extracts significantly
      correlated (P < 0.02) with the phenolic content of the methanolic extracts.
      Ascorbic acid taken as control showed highest antioxidant power in the present
      study. 

PMID- 25374683
TI  - Aurones: a promising heterocyclic scaffold for the development of potent
      antileishmanial agents.
AB  - A series of (Z)-2-benzylidenebenzofuran-3-(2H)-ones (aurones) bearing a variety
      of substituents on rings A and B were synthesized and evaluated for their
      antiparasitic activity against the intracellular amastigote form of Leishmania
      infantum and their cytotoxicity against human THP1-differentiated macrophages. In
      general, aurones bearing no substituents on ring A (compounds 4a-4f) exhibit
      higher toxicity than aurones with 4,6-dimethoxy substitution (compounds 4g-4l).
      Among the latter, two aurones possessing a 2'-methoxy or a 2'-methyl group
      (compounds 4i and 4j) exhibit potent antileishmanial activity (IC50 = 1.3 +/- 0.1
      MUM and IC50 = 1.6 +/- 0.2 MUM, resp.), comparable to the activity of the
      reference drug Amphotericin B, whereas they present significantly lower
      cytotoxicity than Amphotericin B as deduced by the higher selectivity index. 

PMID- 25374684
TI  - Synthesis and anticonvulsant activity of various mannich and schiff bases of 1,5
      benzodiazepines.
AB  - Benzodiazepines have a various behavioral effects in addition to their anxiolytic
      action. There is every reason to believe that the BZ/GABA receptor complex is
      involved in these effects, since GABAmimetic manipulations modify the effect of
      BZ in tests of convulsive activity, motor function, and appetitive behavior. 1,5
      Benzodiazepines are biologically important molecules and are extensively used
      clinically as analgesic, hypnotic, sedative, and antidepressive agents. Hence,
      1,5-Benzodiazepines were synthesized by condensation of o-phenylenediamine and
      ketones, for example, cyclohexanone and acetone in presence of sulfated zirconia
      (catalyst). Mannich bases were synthesized with acetophenone, p
      nitroacetophenone, p-chloroacetophenone, and formaldehyde. Schiff bases were
      synthesized using Mannich base of 1,5-benzodiazepines with p-chloroaniline and p
      chlorophenylsemicarbazide in the presence of glacial acetic acid. All the
      synthesized compounds were characterized by (1)H NMR and IR spectral analyses.
      All the synthesized derivatives were evaluated at the dose of 30 mg/kg b.w for
      anticonvulsant activity by isoniazid induced convulsion model, and the compounds
      NBZD-3 and NBZD-8 were found to be the most active among all compounds. Among all
      the synthesized derivatives, compounds NBZD-13 and NBZD-17 were found to be the
      most active among all compounds using thiosemicarbazide induced model. Although
      NBZD-8, NBZD-10, and NBZD-18 are the compounds which had shown good
      anticonvulsant activity and have an advantage over that, they were not sedative. 

PMID- 25374685
TI  - In Silico Inhibition Studies of Jun-Fos-DNA Complex Formation by Curcumin
      Derivatives.
AB  - Activator protein-1 (AP1) is a transcription factor that consists of the Jun and
      Fos family proteins. It regulates gene expression in response to a variety of
      stimuli and controls cellular processes including proliferation, transformation,
      inflammation, and innate immune responses. AP1 binds specifically to 12-O
      tetradecanoylphorbol-13-acetate (TPA) responsive element 5'-TGAG/CTCA-3' (AP1
      site). It has been found constitutively active in breast, ovarian, cervical, and
      lung cancers. Numerous studies have shown that inhibition of AP1 could be a
      promising strategy for cancer therapeutic applications. The present in silico
      study provides insights into the inhibition of Jun-Fos-DNA complex formation by
      curcumin derivatives. These derivatives interact with the amino acid residues
      like Arg155 and Arg158 which play a key role in binding of Jun-Fos complex to DNA
      (AP1 site). Ala151, Ala275, Leu283, and Ile286 were the residues present at
      binding site which could contribute to hydrophobic contacts with inhibitor
      molecules. Curcumin sulphate was predicted to be the most potent inhibitor
      amongst all the natural curcumin derivatives docked. 

PMID- 25374686
TI  - Room temperature synthesis and antibacterial activity of new sulfonamides
      containing n,n-diethyl-substituted amido moieties.
AB  - Sulfonamide drugs which have brought about an antibiotic revolution in medicine
      are associated with a wide range of biological activities. We have synthesized a
      series of alpha-tolylsulfonamide, 1-11 and their substituted N,N-diethyl-2
      (phenylmethylsulfonamido) alkanamide derivatives, 12-22 in improved and excellent
      yields in aqueous medium at room temperature through highly economical synthetic
      routes. The chemical structures of the synthesized compounds 1-22 were confirmed
      by analytical and spectral data such as IR, (1)H- and (13)C-NMR, and mass
      spectra. The in vitro antibacterial activity of these compounds along with
      standard clinical reference, streptomycin, was investigated on two key targeted
      organisms. It was observed that 1-(benzylsulfonyl)pyrrolidine-2-carboxylic acid,
      2 emerged as the most active compound against Staphylococcus aureus at MIC value
      of 1.8 MUg/mL while 4-(3-(diethylamino)-3-oxo-2-(phenylmethylsulfonamido)
      propyl)phenyl phenylmethanesulfonate, 22 was the most active sulfonamide scaffold
      on Escherichia coli at MIC value of 12.5 MUg/mL. 

PMID- 25374687
TI  - Syntheses and in vitro biological activity of some derivatives of C-9154
      antibiotic.
AB  - In our continued attempts at designing new antibiotics based on the structure of
      the C-9154 antibiotic, to simultaneously improve activity and lower toxicity, an
      analogue to the C-9154 antibiotic and six derivatives of this analogue were
      synthesized. The approach was to significantly reduce the polarity of the
      synthesized analogue in the derivatives to achieve increased permeability across
      cell membranes by conversion of the highly polar carboxylic group to an ester
      functional group. The compounds were synthesized using a two-step reaction which
      involved an additional reaction between benzyl amine and maleic anhydride and
      then conversion of the terminal carboxylic acid functional group to an ester
      functional group using a thionyl chloride mediated esterification reaction. The
      compounds were fully characterized using Infrared, GC-MS, and 1D and 2D NMR
      experiments. The in vitro biological activity of the compounds showed that the
      derivatives were more active than the analogues as was anticipated with minimum
      inhibitory concentration in the range 0.625-5 MUg/mL. The analogue had minimum
      inhibitory concentration in the range 2.5-10 MUg/mL. These values are
      significantly better than that obtained for the original C-9154 antibiotic which
      had activity in the range 10->100 MUg/mL. 

PMID- 25374688
TI  - Synthesis of N-(6-(4-(Piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide
      Derivatives for the Treatment of Metabolic Syndrome.
AB  - Metabolic syndrome is a widely prevalent multifactorial disorder associated with
      an increased risk of cardiovascular disease and type 2 diabetes mellitus. High
      plasma levels of insulin and glucose due to insulin resistance are a major
      component of the metabolic disorder. Thiazolidinediones (TZDs) are potent
      PPARgamma ligand and used as insulin sensitizers in the treatment of type 2
      diabetes mellitus. They are potent insulin-sensitizing agents but due to adverse
      effects like hepatotoxicity, a safer alternative of TZDs is highly demanded. Here
      we report synthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3
      yl)benzenesulfonamide derivatives as an alternate remedy for insulin resistance. 

PMID- 25374689
TI  - Catalyst-free synthesis of highly biologically active 5-arylidene rhodanine and
      2,4-thiazolidinedione derivatives using aldonitrones in polyethylene glycol.
AB  - A green, efficient synthesis of 5-arylidene rhodanine and 2,4-thiazolidinedione
      derivatives without using any external catalyst in polyethylene glycol (PEG) at
      80 degrees C has been described. Reaction procedure is very simple, short, and
      obtained yields are very high. 

PMID- 25374690
TI  - Synthesis Characterization and Antibacterial, Antifungal Activity of N-(Benzyl
      Carbamoyl or Carbamothioyl)-2-hydroxy Substituted Benzamide and 2-Benzyl Amino
      Substituted Benzoxazines.
AB  - New N-(benzyl carbamothioyl)-2-hydroxy substituted benzamides 13, 20, and 21 were
      synthesized using sodium bicarbonate and benzyl amine with 2-thioxo-substituted
      1,3-benzoxazines 6, 10a, b, 11c, and 12a-n. The 2-thioxo-substituted-1,3-oxazines
      6, 10a-b, 11d 12a-n, and 26 were converted to the corresponding 2-methylthio
      substituted-1,3-oxazines 14a-l and 24 which were then converted to 2-benzyl amino
      substituted-benzoxazines 15a-i by refluxing with benzylamine. Products 15a, b, e,
      f, and g were also synthesized by boiling the corresponding N-(benzyl
      carbamothioyl)-2-hydroxy substituted benzamides 13a, b, f, l, and m in acetic
      acid. 2-Oxo-substituted-1,3-benzoxazines 22 and 25 were prepared by treating the
      corresponding 2-methylthio-substituted-1,3-oxazines 14 and 24 with dilute HCl.
      The N-(benzyl carbamoyl)-2-hydroxy substituted benzamide 23 was synthesized from
      the reaction of 2-oxo-substituted-1,3-benzoxazine 22 with benzylamine. The new
      products were characterized using IR, (1)H, and (13)C NMR in addition to
      microanalysis. Selected compounds were tested in vitro for antibacterial and
      antifungi activity and the most active compounds were found to be the 4
      (substituted-benzylamino)-2-hydroxy benzoic acids 9a and d (M. chlorophenolicum,
      MIC 50 and 25 ugm L(-1), resp.), N1, N3-bis (benzyl carbamothioyl)-4,6-dihydroxy
      substituted phthalamides 20a and 20c (B. subtilis MIC 12.5, 50 ugm L(-1), resp.)
      and 21 (M. chlorophenolicum, MIC 50 ugm L(-1)). 

PMID- 25374691
TI  - The Development of Models Based on Linear and Nonlinear Multivariate Methods to
      Predict ADME/PK Properties Using Physicochemical Properties of Kinase, Protease
      Inhibitors, and GPCR Antagonists.
AB  - Oral bioavailability of a drug compound is the significant property for potential
      drug candidates. Measuring this property can be costly and time-consuming.
      Quantitative structure-property relationships (QSPRs) are used to estimate the
      percentage of oral bioavailability, and they are an attractive alternative to
      experimental measurements. A data set of 217 drug and drug-like compounds with
      measured values of the percentage of oral bioavailability taken from the small
      molecule ChemBioBase database was used to develop and test a QSPR model.
      Descriptors were calculated for the compounds using Codessa 2.1 tool. Nonlinear
      general regression neural network model was generated using the DTREG predictive
      modeling program software. The calculated percentage of oral bioavailability
      model performs well, with root-mean-square (rms) errors of 4.55% oral
      bioavailability units for the training set, 14.32% oral bioavailability units for
      the test set, and 19.12% oral bioavailability units for the external prediction
      set. Given the structural diversity and bias of the data set, this is a good
      first attempt at modeling oral bioavailability using QSPR methods. The model can
      be used as a potential virtual screen or property estimator. With a larger data
      supply less biased toward the high end values of the percentage of oral
      bioavailability, a more successful model could likely be developed. 

PMID- 25374692
TI  - HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens.
AB  - The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules
      are indispensable for the studies on the functions at molecular level. We have
      developed a homology modeling system named HLA-modeler specialized in the HLA
      molecules. Segment matching algorithm is employed for modeling and the
      optimization of the model is carried out by use of the PFROSST force field
      considering the implicit solvent model. In order to efficiently construct the
      homology models, HLA-modeler uses a local database of the 3D structures of HLA
      molecules. The structure of the antigenic peptide-binding site is important for
      the function and the 3D structure is highly conserved between various alleles.
      HLA-modeler optimizes the use of this structural motif. The leave-one-out cross
      validation using the crystal structures of class I and class II HLA molecules has
      demonstrated that the rmsds of nonhydrogen atoms of the sites between homology
      models and crystal structures are less than 1.0 A in most cases. The results have
      indicated that the 3D structures of the antigenic peptide-binding sites can be
      reproduced by HLA-modeler at the level almost corresponding to the crystal
      structures. 

PMID- 25374693
TI  - Synthesis and In Vitro Antimicrobial Evaluation of New 1,3,4-Oxadiazoles Bearing
      5-Chloro-2-methoxyphenyl Moiety.
AB  - A series of new 1,3,4-oxadiazole derivatives, 4(a-h), containing 5-chloro-2
      methoxy benzohydrazide moiety were synthesized by the reaction of 5-chloro-2
      methoxybenzoate with different aromatic carboxylic acids. These newly synthesized
      compounds were characterized by FT-IR, (1)H NMR, mass spectra, and also by
      elemental analysis. All the newly synthesized compounds were screened for their
      antibacterial and antifungal activities. Antimicrobial studies revealed that
      compounds 4c, 4f, and 4g showed significant activity against tested strains. 

PMID- 25374695
TI  - Photoelastic and finite element analyses of occlusal loads in mandibular body.
AB  - This study proposed to evaluate the mandibular biomechanics in the posterior
      dentition based on experimental and computational analyses. The analyses were
      performed on a model of human mandible, which was modeled by epoxy resin for
      photoelastic analysis and by computer-aided design for finite element analysis.
      To standardize the evaluation, specific areas were determined at the lateral
      surface of mandibular body. The photoelastic analysis was configured through a
      vertical load on the first upper molar and fixed support at the ramus of
      mandible. The same configuration was used in the computer simulation. Force
      magnitudes of 50, 100, 150, and 200 N were applied to evaluate the bone stress.
      The stress results presented similar distribution in both analyses, with the more
      intense stress being at retromolar area and oblique line and alveolar process at
      molar level. This study presented the similarity of results in the experimental
      and computational analyses and, thus, showed the high importance of morphology
      biomechanical characterization at posterior dentition. 

PMID- 25374696
TI  - A Novel Cryptic Three-Way Translocation t(2;9;18)(p23.2;p21.3;q21.33) with
      Deletion of Tumor Suppressor Genes in 9p21.3 and 13q14 in a T-Cell Acute
      Lymphoblastic Leukemia.
AB  - Acute leukemia often presents with pure chromosomal resolution; thus, aberrations
      may not be detected by banding cytogenetics. Here, a case of 26-year-old male
      diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and a normal karyotype
      after standard GTG-banding was studied retrospectively in detail by molecular
      cytogenetic and molecular approaches. Besides fluorescence in situ hybridization
      (FISH), multiplex ligation-dependent probe amplification (MLPA) and high
      resolution array-comparative genomic hybridization (aCGH) were applied. Thus,
      cryptic chromosomal aberrations not observed before were detected: three
      chromosomes were involved in a cytogenetically balanced occurring translocation
      t(2;9;18)(p23.2;p21.3;q21.33). Besides a translocation t(10;14)(q24;q11) was
      identified, an aberration known to be common in T-ALL. Due to the three-way
      translocation deletion of tumor suppressor genes CDKN2A/INK4A/p16,
      CDKN2B/INK4B/p15, and MTAP/ARF/p14 in 9p21.3 took place. Additionally RB1 in
      13q14 was deleted. This patient, considered to have a normal karyotype after low
      resolution banding cytogenetics, was treated according to general protocol of
      anticancer therapy (ALL-BFM 95). 

PMID- 25374697
TI  - Total knee arthroplasty designed to accommodate the presence or absence of the
      posterior cruciate ligament.
AB  - Evidence for selecting the same total knee arthroplasty prosthesis whether the
      posterior cruciate ligament (PCL) is retained or resected is rarely documented.
      This study reports prospective midterm clinical, radiographic, and functional
      outcomes of a fixed-bearing design implanted using two different surgical
      techniques. The PCL was completely retained in 116 knees and completely resected
      in 43 knees. For the entire cohort, clinical knee (96 +/- 7) and function (92 +/-
      13) scores and radiographic outcomes were good to excellent for 84% of patients
      after 5-10 years in vivo. Range of motion averaged 124 degrees  +/- 9 degrees ,
      with 126 knees exhibiting >=120 degrees  flexion. Small differences in average
      knee flexion and function scores were noted, with the PCL-resected group
      exhibiting an average of 5 degrees  more flexion but an average function score
      that was 7 points lower compared to the PCL-retained group. Fluoroscopic analysis
      of 33 knees revealed stable tibiofemoral translations. This study demonstrates
      that a TKA articular design with progressive congruency in the lateral
      compartment can provide for femoral condyle rollback in maximal flexion
      activities and achieve good clinical and functional performance in patients with
      PCL-retained and PCL-resected TKA. This TKA design proved suitable for use with
      either surgical technique, providing surgeons with the choice of maintaining or
      sacrificing the PCL. 

PMID- 25374698
TI  - Manipulation of displaced distal radial fractures in the superelderly: prediction
      of malunion and the degree of radiographic improvement.
AB  - Superelderly patients (>=80 years old) account for 20% of all distal radial
      fractures and are at an increased risk of malunion. The primary aim of this study
      was to identify predictors of malunion and the degree of improvement in the
      fracture position offered by closed manipulation of displaced distal radial
      fractures in the superelderly. We retrospectively identified 228 displaced distal
      radial fractures in superelderly patients from a prospective database of 4024
      distal radial fractures. The inclusion criterion was a patient that underwent
      closed manipulation as their primary intervention. The majority of patients (n =
      196, 86%) were defined as having a malunion. A premanipulation dorsal angulation
      of greater than 25 degrees (P = 0.047) and an ulnar variance of 6 mm or more (P =
      0.02) significantly increased the risk of malunion. The premanipulation dorsal
      angulation was a significant independent predictor of the degree of improvement
      in the final dorsal angulation (P < 0.001) and ulnar variance (P = 0.01).
      Patients with a high risk of malunion or poor improvement in the fracture
      position can be identified before manipulation and these patients may benefit
      from primary surgical intervention. 

PMID- 25374694
TI  - The contribution of immune and glial cell types in experimental autoimmune
      encephalomyelitis and multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system characterised by widespread areas of focal demyelination. Its aetiology
      and pathogenesis remain unclear despite substantial insights gained through
      studies of animal models, most notably experimental autoimmune encephalomyelitis
      (EAE). MS is widely believed to be immune-mediated and pathologically
      attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS
      research has expanded beyond its focus on CD4+ T cells to recognise the
      contributions of multiple immune and glial cell types to the development,
      progression, and amelioration of the disease. This review summarises evidence of
      T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and
      oligodendroglial involvement in both EAE and MS and the intercommunication and
      influence of each cell subset in the inflammatory process. Despite important
      advances in the understanding of the involvement of these cell types in MS, many
      questions still remain regarding the various subsets within each cell population
      and their exact contribution to different stages of the disease. 

PMID- 25374699
TI  - Intravenous Lormetazepam during Sedation Weaning in a 26-Year-Old Critically Ill
      Woman.
AB  - Recent evidence revealed that sedation is related to adverse outcomes including a
      higher mortality. Despite this fact, patients sometimes require deep sedation for
      a limited period of time to control, for example, intracranial hypertension. In
      particular in these cases, weaning from sedation is often challenging due to
      emerging agitation, stress, and delirium. The submitted research letter reports a
      rare case of severe and persisting agitation that was unresponsive to all
      available treatments. Ultimately, lormetazepam which has recently become
      available for intravenous use in Germany resolved the problem by stress-reduction
      and anxiolysis without leading to measurable sedation. 

PMID- 25374701
TI  - Retracted: Primary small cell undifferentiated (neuroendocrine) carcinoma of the
      maxillary sinus.

PMID- 25374700
TI  - Hyperplastic dental follicle: a case report and literature review.
AB  - Hyperplastic dental follicle is an odontogenic hamartomatous lesion associated
      with delayed or tooth eruption failure in young patients. The occurrence of this
      pericoronal dental lesion may be single or multiple and it seems to be more
      frequent than literature has reported. We present a literature review focusing on
      the etiopathogenesis and clinicopathological features of this hamartomatous
      lesion in young patients. In addition, we reported a case of hyperplastic dental
      follicle causing delayed tooth eruption of 14-year-old male patient. Microscopic
      analyses based on routine staining and immunohistochemistry were used to discuss
      the cells found in pericoronal follicle. This paper reinforces the importance of
      association between clinical history and radiographic features with microscopic
      pericoronal follicle examination for diagnosis of this hamartomatous lesion. 

PMID- 25374702
TI  - Iatrogenic anetoderma of prematurity: a case report and review of the literature.
AB  - Anetoderma is a skin disorder characterized by focal loss of elastic tissue in
      the mid dermis, resulting in localized areas of macular depressions or pouchlike
      herniations of skin. An iatrogenic form of anetoderma has been rarely described
      in extremely premature infants and has been related to the placement of
      monitoring devices on the patient skin. Because of the increasing survival of
      extremely premature infants, it is easy to foresee that the prevalence of
      anetoderma of prematurity will increase in the next future. Although it is a
      benign lesion, it persists over time and can lead to significant aesthetic damage
      with need for surgical correction. Sometimes the diagnosis can be difficult,
      especially when the atrophic lesions become evident after discharge. Here, we
      report on a premature infant born at 24 weeks of gestation, who developed
      multiple anetodermic patches of skin on the trunk at the sites where
      electrocardiographic electrodes were previously applied. The knowledge of the
      disease can encourage a more careful management of the skin of extremely
      premature babies and aid the physicians to diagnose the disease when anetoderma
      patches are first encountered later in childhood. 

PMID- 25374703
TI  - Acute acalculous cholecystitis induced by acute hepatitis B virus infection.
AB  - During the course of acute viral hepatitis, some functional and anatomical
      changes to the gallbladder can occur. Acute acalculous cholecystitis (ACC) is a
      rare complication of acute hepatitis B virus infection; only few cases are
      reported as ACC associated with acute hepatitis B virus infection. ACC cases are
      self-limiting, while other limited cases can progress to a gangrenous state,
      perforation, and even death. We present a 27-year-old female case diagnosed to
      have acute acalculous cholecystitis and associated with acute hepatitis B virus
      infection, and she recovered within one week of her presentation without
      complication or surgical intervention. 

PMID- 25374704
TI  - Metronidazole-induced encephalopathy in a patient with end-stage liver disease.
AB  - Purpose. Metronidazole-induced encephalopathy (MIE) has been rarely reported. We
      report a case in a patient with end-stage liver disease (ESLD). Summary. A 63
      year-old male with ESLD secondary to hepatitis C virus presented with
      progressively worsening fatigue, slurred speech, aphasia, vomiting, and left
      sided facial droop after completing a 2-week course of metronidazole for
      recurrent Clostridium difficile-associated diarrhea. He completed a previous
      course of metronidazole 3 weeks prior to presentation. He is on the liver
      transplant waiting list and has known hepatic encephalopathy. MRI revealed
      hyperintense T2 signals involving the bilateral dentate nuclei, inferior
      colliculi and splenium of the corpus callosum, and increased diffusion
      restriction at the splenium of the corpus callosum. His neurological function
      improved over the next several days. He underwent liver transplantation 6 days
      after admission. A follow-up MRI 6 weeks after presentation revealed resolution
      of abnormalities; however, paresthesias persisted 6 months after MIE diagnosis.
      Conclusion. An ESLD patient with hepatic encephalopathy developed MIE after a
      relatively short course of metronidazole. Metronidazole has been shown to
      accumulate in patients with ESLD. Increased awareness for neurotoxicity when
      using metronidazole in ESLD patients is warranted, especially in those with
      potentially confounding hepatic encephalopathy. 

PMID- 25374705
TI  - Hepatobiliary cystadenocarcinoma.
AB  - Biliary cystadenocarcinomas are rare tumors that are poorly understood.
      Preoperative imaging is imprecise and treatment is not standardized. We describe
      the presentation and treatment of one of these rare tumors and review the limited
      published literature. 

PMID- 25374706
TI  - Rare case of adult undifferentiated (embryonal) sarcoma of the liver treated with
      liver transplantation: excellent long-term survival.
AB  - We present the case of a 54-year-old gentleman who presented with abdominal
      distension and a CT scan of his abdomen revealed a large (25 cm) left hepatic
      lobe tumor. He received chemotherapy for over 1.5 years. The CT scans at the
      completion of this therapy revealed that the tumor had actually slightly grown in
      size. He underwent orthotopic liver transplantation without any major
      complications. The explant histopathology revealed an undifferentiated embryonal
      cell sarcoma (UECS) composed of relatively bland spindled cells arranged in short
      fascicles. It is now 10 years and 3 months since his last transplant and the
      patient remains well with no tumor recurrence. 

PMID- 25374707
TI  - A case of hepatic angiomyolipoma which was misdiagnosed as hepatocellular
      carcinoma in a hepatitis B carrier.
AB  - We report a rare case of resected hepatic AML, which was misdiagnosed as
      hepatocellular carcinoma in a chronic hepatitis B carrier. A 45-year-old woman
      who was a carrier of hepatitis B virus infection presented with a hepatic tumor.
      Her serum alpha-fetoprotein level was normal. Ultrasonography revealed a round
      and well-circumscribed echogenic hepatic tumor measuring 2.5 cm in the segment
      VI. On contrast-enhanced computed tomography, a hypervascular tumor was observed
      in the arterial phase and washing-out of the contrast medium in the portal phase
      and delayed phase. On MR T1-weighted in-phase images, the mass showed low signal
      intensity, and on out-of-phase images, the mass showed signal drop and dark
      signal intensity. On MR T2-weighted images, the mass showed high signal
      intensity. The mass demonstrated high signal intensity on arterial phase after
      contrast injection, suggestive of hepatocellular carcinoma. The patient underwent
      hepatic wedge resection and histopathological diagnosis was a hepatic
      angiomyolipoma. 

PMID- 25374708
TI  - Systemic mastocytosis: a rare case of increased liver stiffness.
AB  - Assessment of liver stiffness (LS) by transient elastography (Fibroscan) has
      significantly improved the noninvasive diagnosis of liver fibrosis. We here
      report on a 55-year-old patient with drastically increased LS due to previously
      unknown systemic mastocytosis. The patient initially presented with increased
      weight loss, nocturnal pruritus, increased transaminases, bilirubinemia, and
      thrombocytopenia. Abdominal ultrasound showed ascites, hepatomegaly, and
      splenomegaly. In addition, LS was 75 kPa (IQR 0 kPa) clearly exceeding the cut
      off value for F4 cirrhosis of 12.5 kPa. However, histological analysis of the
      liver specimen indicated liver involvement by systemic mastocytosis and excluded
      liver cirrhosis. An additional CT scan detected disseminated bone lesions. After
      three months of treatment with Midostaurin, LS slightly decreased down to 31.9
      kPa (IQR 8.3 kPa). This case illustrates that diffused sinusoidal neoplastic
      infiltrates are a pitfall in the non-invasive diagnosis of liver cirrhosis. In
      conclusion, refined clinical algorithms for increased LS should also include
      mastocytosis in addition to inflammation, congestion, and biliary obstruction. 

PMID- 25374709
TI  - Hepatic myelopathy in a patient with decompensated alcoholic cirrhosis and portal
      colopathy.
AB  - Cirrhotic or hepatic myelopathy is a rare neurological complication of chronic
      liver disease usually seen in adults and presents as a progressive pure motor
      spastic paraparesis which is usually associated with overt liver failure and a
      surgical or spontaneous systemic portocaval shunt. We describe the development of
      progressive spastic paraparesis, in a patient with alcoholic cirrhosis with
      portal hypertension and portal colopathy who presented with the first episode of
      hepatic encephalopathy. The patient had not undergone any shunt procedure. 

PMID- 25374710
TI  - Biliary adenofibroma with carcinoma in situ: a rare case report.
AB  - This case report exhibits a rare biliary tumor within the liver of a 53-year-old
      Caucasian woman. This exophytic, multicystic, 6.5 * 5.0 cm mass was composed of
      complex tubulocystic structures lined by nonmucin-secreting, biliary epithelium
      embedded in fibrous stroma, consistent with biliary adenofibroma. This is the
      seventh case described in the literature. Multiple foci of high-grade
      dysplasia/carcinoma in situ were found with a microscopic focus of invasive
      carcinoma in review of the pathology, making this only the second case reporting
      malignant transformation. It is presented to illustrate the premalignant
      potential in a biliary epithelial tumor currently categorized as benign. 

PMID- 25374711
TI  - Asymptomatic Liver Abscesses Mimicking Metastases in Patients after Whipple
      Surgery: Infectious Complications following Percutaneous Biopsy-A Report of Two
      Cases.
AB  - We present two cases of hepatic abscesses that mimicked metastases in patients
      having undergone Whipple surgery. Both patients had similar imaging features on
      computed tomographic (CT) scan and ultrasound, and at the time of referral for
      biopsy neither patient was clinically suspected to have liver abscess. Both
      patients underwent biopsy of liver lesions and developed postprocedural
      infectious complications. 

PMID- 25374712
TI  - Combined hepatocellular carcinoma and fibrolamellar carcinoma presenting as two
      adjacent separate lesions in a young boy: first case report from Asia.
AB  - We report a rare case of combined hepatocellular carcinoma and fibrolamellar
      carcinoma arising in a noncirrhotic liver, in a 14-year-old boy who underwent
      right hepatectomy. We discuss the clinicopathological and immunohistochemical
      features and the clinical outcome in this unusual tumor. 

PMID- 25374713
TI  - Surviving emphysematous gastritis after hepatectomy.
AB  - Emphysematous gastritis is a rare variant of phlegmonous gastritis due to
      invasion of stomach wall by gas-forming bacteria. It is characterised by abnormal
      presence of gas in the stomach by imaging, in association with clinical sepsis.
      Patients suffering from this condition usually present with an underlying
      pathology. We are reporting a middle-aged Chinese male with hepatitis B virus
      related hepatocellular carcinoma. He underwent partial hepatectomy and was
      diagnosed with emphysematous gastritis 4 days after index operation. Emergency
      laparotomy, including upper endoscopy, was performed. He was managed with
      antibiotics and discharged 18 days after second operation. This paper shows a
      review of the literature about the disease, with particular attention to
      pathology, clinical features, and management. 

PMID- 25374714
TI  - Conservative treatment for cystic duct stenosis in a child.
AB  - Introduction. Few cases of common bile duct stenosis have been reported in the
      literature, and observations of strictures in the cystic duct are even more rare.
      Surgical cholecystectomy is the treatment needed in most cases of gallbladder
      hydrops. This paper describes the diagnosis and successful medical treatment of a
      rare pediatric case of cystic duct stenosis and gallbladder hydrops. Case Report.
      A formerly healthy one-year-old girl was admitted with colicky abdominal pain.
      Blood tests were normal, except for an increase in transaminases. Abdominal
      ultrasound excluded intestinal intussusception and identified a distended
      gallbladder with biliary sludge. MR cholangiography revealed a dilated
      gallbladder containing bile sediment and no detectable cystic duct, while the
      rest of the intra- and extrahepatic biliary tree and hepatic parenchyma were
      normal. This evidence was consistent with gallbladder hydrops associated with
      cystic duct stenosis. The baby was treated with i.v. hydration, corticosteroids,
      antibiotics, and ursodeoxycholic acid. Her general condition rapidly improved,
      with no further episodes of abdominal pain and normalization of liver enzymes.
      This allowed to avoid cholecystectomy, and the child is well 1.5 years after
      diagnosis. Conclusions. Although cholecystectomy is usually necessary in case of
      gallbladder hydrops, our experience suggests that surgical procedures can be
      avoided when the distension is caused by a cystic duct stenosis. 

PMID- 25374715
TI  - Primary pleomorphic liposarcoma of liver: a case report and review of the
      literature.
AB  - Primary liver liposarcoma is a rare disease. The knowledge of the clinical
      course, management, and prognosis of primary liver liposarcoma are all limited
      because of its rarity. Twelve cases of primary liposarcoma of the liver have been
      previously reported. We present the thirteenth case, which occurred in an adult
      male patient. A 42-year-old male patient came to our outpatient department with
      complaints of pain abdomen, mass per abdomen, and weight loss. Ultrasonography
      showed a mass arising from the the left lobe of liver. CT abdomen showed a
      heterogenous enhancing mass from left lobe of liver with multiple cystic and
      necrotic areas compressing the stomach and spleen with no evidence of metastasis.
      Differential diagnosis included adenoma and primary malignancy. Exploratory
      laparotomy and resection were done. HPE was found to be pleomorphic liposarcoma
      of liver. 

PMID- 25374716
TI  - Death from Liver Failure despite Lamivudine Prophylaxis during R-CHOP
      Chemotherapy due to Rapid Emergence M204 Mutations.
AB  - Background. Rapid and early emergence of clinically significant LAM resistance is
      thought to be unlikely during the first year of treatment, and as a result LAM is
      thought to be a reasonable choice as a first line agent for prophylaxis during
      chemotherapy. Aim. To report fatal HBV reactivation despite appropriate LAM
      prophylaxis in two previously treatment-naive individuals undergoing R-CHOP
      chemotherapy. Case Presentation. Case 1 is a 65-year-old man with chronic HBV
      infection: HBeAg-negative, HBV DNA 6.65E5 IU/mL, ALT 43 IU/L, and Fibroscan 4.4
      kPa, consistent with F0, who was diagnosed with lymphoma that was treated with R
      CHOP and LAM prophylaxis. HBV DNA fell to 2.18E1 IU/mL within 2 months of
      starting LAM. Four months after chemotherapy, despite ongoing LAM of 7-month
      duration with confirmed adherence, severe asymptomatic hepatitis was noted during
      routine monitoring with ALT 1019 IU/L, HBeAg negative, HBV DNA 1.43E7 IU/mL, and
      genotyping confirmed L80I and M204I mutations. He died 14 days after flare
      diagnosis despite a switch to tenofovir (HBV DNA had fallen to 1.94E5 IU/mL 2
      weeks after starting tenofovir). Case 2 is a 50-year-old man who was found to
      have HBeAg-negative hepatitis B, ALT 37 IU/L, and no clinical features of
      cirrhosis (platelets 283, APRI 0.19) after lymphoma diagnosis. Lymphoma was
      treated with R-CHOP and LAM prophylaxis. Pretreatment HBV DNA was not done but
      was 8.90E4 IU/mL 3 weeks after starting LAM and 3.96E3 IU/mL 3 months after
      starting LAM. Two months after chemotherapy, despite ongoing LAM of 7-month
      duration with confirmed adherence, severe symptomatic hepatitis presenting with
      jaundice, abdominal pain, and confusion was noted. ALT 902 IU/L, HBeAg negative,
      HBV DNA 1.02E8 IU/mL, and genotyping confirmed L80I, M80V, and M204V/S mutations.
      He died 3 days after flare diagnosis despite the addition of tenofovir.
      Conclusion. Lamivudine should not be used for prophylaxis of patients with
      chronic hepatitis B with detectable HBV DNA undergoing chemotherapy with
      rituximab containing cytotoxic chemotherapy even if they have never had exposure
      to lamivudine in the past. In this setting, lamivudine failure due to resistance
      can develop quickly leading to liver failure that cannot be salvaged with
      tenofovir. Whether LAM is safe for prophylaxis with rituximab-based cytotoxic
      chemotherapy for patients with undetectable HBV DNA is unknown, but agents with a
      high barrier to resistance may be preferable. 

PMID- 25374717
TI  - Hepatitis B virus reactivation induced by infliximab administration in a patient
      with Crohn's disease.
AB  - A 47-year-old man diagnosed with Crohn's disease was treated with infliximab. He
      tested negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface
      antibody (anti-HBs) but positive for anti-HB core antibody (anti-HBc). He tested
      positive for hepatitis B virus (HBV-) DNA 3 months after treatment and was
      administered entecavir. HBV-DNA test showed negative results 1 month later. ALT
      was persistently within the normal range, and HBV-DNA was persistently negative
      thereafter despite the continuation of infliximab every 8 weeks. In our hospital,
      14 patients with inflammatory bowel disease, who tested negative for HBsAg, were
      treated with infliximab; 2 of them tested positive for anti-HBs and/or anti-HBc,
      and HBV reactivation was observed in 1 patient (the present patient). The present
      case and these findings highlight that careful follow-up is needed in patients
      with inflammatory bowel disease treated with infliximab who test positive for
      anti-HBc and/or anti-HBs. 

PMID- 25374718
TI  - An unusual congenital in situ malrotation of the liver.
AB  - Congenital anomaly of the liver is an uncommon and usually incidental finding.
      This report describes a case of in situ liver malrotation that has never been
      reported in the literature. Published literature relevant to the finding are
      briefly discussed. 

PMID- 25374719
TI  - Fulminant liver failure associated with abdominal crush injury in an eleven-year
      old: a case report.
AB  - An 11-year-old obese male was involved in an all-terrain vehicle rollover
      accident. He had elevated transaminase levels along with a lactic acidosis. The
      imaging studies did not reveal any major intra-abdominal or thoracic injuries.
      The physical exam was unremarkable. The patient had an unremarkable PICU course
      and was transferred to the floor the next day. Within 24 hours of his transfer,
      he was noted to have interval worsening in liver function tests. He developed
      fulminant liver failure (FLF), renal failure, and encephalopathy. An ultrasound
      of the liver revealed increased echogenicity in the right lobe with focal
      sparing. Patient was listed for transplant. Investigations into any underlying
      medical cause of FLF were negative. Liver failure was presumed to be related to
      ischemia/reperfusion injury of the liver. The renal failure was due to
      rhabdomyolysis and was supported with renal replacement therapy. Patient received
      supportive care for FLF and was noted to have significant recovery of liver and
      renal function with time. He was discharged home after a 3-week hospitalization.
      Patients with crush abdominal injuries and elevated transaminase levels without
      evidence of parenchymal liver disruption may need to be closely monitored for
      liver failure related to ischemia reperfusion. 

PMID- 25374720
TI  - Pleuro-Pulmonary Nocardiosis as Opportunistic Infection in a Patient with Chronic
      Hepatitis C under Combination Treatment with Pegylated Interferon, Ribavirin, and
      Boceprevir.
AB  - Nocardiosis is an infrequent but serious pulmonary infection caused by Gram
      positive aerobic actinomycetes. In this paper, we report on a 48-year-old patient
      with pleuropulmonary nocardiosis and cirrhosis due to chronic hepatitis C virus
      infection treated with triple antiviral treatment complicated by prolonged
      neutropenia. 

PMID- 25374721
TI  - Acute pancreatitis complicating acute hepatitis e virus infection: a case report
      and review.
AB  - Acute pancreatitis complicating fulminant viral hepatitis has been well
      recognized; however, acute pancreatitis occurring in nonfulminant hepatitis is
      very rare. The case presented describes moderate pancreatitis in a young male,
      manifesting during the course of nonfulminant acute hepatitis E infection. The
      diagnosis of acute viral hepatitis E was confirmed by serology and reverse
      transcriptase polymerase chain reaction (RT-PCR) to demonstrate Hepatitis E virus
      (HEV) RNA in both stool and serum. Patients with acute viral hepatitis presenting
      with severe abdominal pain should have a diagnosis of acute pancreatitis
      suspected and appropriate investigations including serum amylase, lipase, biliary
      ultrasonography and/or contrast-enhanced computed tomography of the abdomen
      should be undertaken. The identification of this unusual complication of
      Hepatitis E is important; however, the prognosis for patients with Acute
      Pancreatitis Complicating Acute Hepatitis E Virus Infection is good, and
      uncomplicated recovery with conservative treatment is expected. 

PMID- 25374722
TI  - Acute abdomen secondary to incarcerated umbilical hernia after treatment of
      massive cirrhotic ascites.
AB  - Umbilical herniation is common in patients with liver cirrhosis and ascites.
      Rarely, they suffer from incarceration and strangulation of the umbilical hernia
      after treatment of ascites. We report 3 cases of umbilical hernia incarceration
      following removal of massive ascites with different treatment modalities.
      Physicians managing this group of patients should be aware of this rare and
      potentially fatal complication. 

PMID- 25374723
TI  - Tocilizumab-Induced Acute Liver Injury in Adult Onset Still's Disease.
AB  - Background. Tocilizumab, a monoclonal humanized anti-IL-6 receptor antibody, is
      used in treatment of refractory adult onset Still's disease (AOSD). Mild to
      moderate liver enzyme elevation is a well-known side effect, but severe liver
      injury has only been reported in 3 cases in the literature. Case. A young female
      suffering from corticoid and methotrexate refractory AOSD was treated by
      tocilizumab. After 19 months of consecutive treatment, she developed acute severe
      liver injury. Liver biopsy showed extensive hepatocellular necrosis with
      ballooned hepatocytes, highly suggestive of drug-induced liver injury. No other
      relevant drug exposure beside tocilizumab was recorded. She recovered totally
      after treatment discontinuation and an initial 3-day course of intravenous N
      acetylcysteine with normalization of liver function tests after 6 weeks.
      Conclusion. Acute severe hepatitis can be associated with tocilizumab as
      documented in this case. Careful monitoring of liver function tests is warranted
      during tocilizumab treatment. 

PMID- 25374724
TI  - Liver metastases of unknown primary: malignant melanoma.
AB  - According to the National Cancer Institute's (NCI) data, the increase in the
      number of patients diagnosed with malignant melanoma was found to be at a higher
      rate than the current increase in all other types of cancer (Jemal et al., 2008).
      Early diagnosis, appropriate surgical treatment, and chemotherapy have positive
      impacts on the course of the disease but despite these developments on the
      treatment, current prognosis of metastatic malignant melanoma prognosis is still
      extremely poor. Life expectancy in patients with metastatic disease is between 2
      and 8 months. The 5-year disease-free survival rate is identified in only 5% of
      the patients (Leong, 2003) (Kirkwood et al., 1996). In this study, we try to
      report a patient with metastatic malignant melanoma and give recent informations
      about the liver metastases of malignant melanoma. 

PMID- 25374725
TI  - Bleeding ectopic varices as the first manifestation of portal hypertension.
AB  - Ectopic varices are defined as dilated portosystemic collateral veins in
      locations other than the gastroesophageal region. We present a case of recurrent
      upper gastrointestinal bleeding as the first manifestation of portal
      hypertension. We diagnosed ectopic duodenal varices without gastroesophageal
      varices on upper GI endoscopy and extrahepatic portal venous obstruction (EHPVO)
      on CT angiography and managed this case. 

PMID- 25374726
TI  - The successful use of inhaled nitric oxide in the management of severe
      hepatopulmonary syndrome after orthotopic liver transplantation.
AB  - Hepatopulmonary syndrome (HPS) is characterized by pulmonary vasodilation and
      subsequent hypoxemia in the setting of hepatic dysfunction. There is currently no
      pharmacologic intervention that has been shown to significantly affect outcomes
      and liver transplantation remains the mainstay of therapy. Unfortunately,
      patients undergoing liver transplantation are at high risk of significant
      hypoxemia and mortality in the early postoperative period. In the following case
      series, we present two cases of patients with severe HPS who underwent liver
      transplantation and experienced marked hypoxemia in the early postoperative
      period. In both cases, we successfully treated the patients with inhaled nitric
      oxide for their severe refractory life-threatening hypoxemia which led to
      immediate and dramatic improvements in their oxygenation. Although the use of
      inhaled nitric oxide in patients with HPS has been sporadically reported in
      pediatric literature and in animal studies, to our knowledge, our cases are the
      first recorded in adult patients. 

PMID- 25374727
TI  - Autoimmune cholangitis: a variant syndrome of autoimmune hepatitis.
AB  - Autoimmune cholangitis (AIC) or autoimmune cholangiopathy is a chronic
      inflammation of liver and a variant syndrome of autoimmune hepatitis (AIH). We
      present a case of an adult female who had biochemical features of cholestasis and
      transaminasemia but aminotransferases were not in the hepatitis range and had
      histological evidence of bile duct injury which was subsequently diagnosed as
      autoimmune cholangitis. 

PMID- 25374728
TI  - External hemorrhage from a portacaval anastomosis in a patient with liver
      cirrhosis.
AB  - Variceal bleeding is the major complication of portal hypertension in patients
      with liver cirrhosis. Hemorrhage mainly occurs in gastrointestinal lumen.
      Extraluminal hemorrhages are quite rare, such as intraperitoneal hemorrhages. We
      aimed to present a variceal bleeding case from the anastomosis on the anterior
      abdominal wall, as an extraordinary bleeding location, in a patient with portal
      hypertension in whom there were no esophageal and gastric varices. 

PMID- 25374729
TI  - The possible efficacy of artichoke in fluconazole related hepatotoxicity.
AB  - Although fluconazole related hepatotoxicity (FRH) is rare, mortal acute hepatic
      necrosis and jaundice were reported in immunocompromised states such as acquired
      immunodeficiency syndrome (AIDS) and bone marrow transplant (BMT). We present a
      case of a patient with multiple sclerosis who developed hepatotoxicity with the
      use of a single 150 mg fluconazole tablet for fungal vaginitis, 10 days after
      methylprednisolone pulse treatment. Our patient's alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST) levels were decreased, 1200 U/L and 800 U/L,
      respectively, and bilirubin levels were consistent at 37 mg/dL. Artichoke which
      has anticholestatic and antioxidant properties was used by our patient. She
      consumed a 30 mg artichoke leaf extract tea 3 times a day. The bilirubin levels
      significantly declined at the end of the first week and all liver function tests
      were normalized within 2 months. 

PMID- 25374730
TI  - Nonalcoholic steatohepatitis in a patient with ataxia-telangiectasia.
AB  - Ataxia-telangiectasia (A-T) is a rare disease characterized by neurodegenerative
      alterations, telangiectasia, primary immunodeficiency, extreme sensitivity to
      radiation, and susceptibility to neoplasms. A-T patients have inactivation of
      ataxia-telangiectasia-mutated (ATM) protein, which controls DNA double-strand
      break repair and is involved in oxidative stress response, among other functions;
      dysfunctional control of reactive oxygen species may be responsible for many of
      the clinical manifestations of this disease. To the best of our knowledge,
      hepatic lesions of steatohepatitis have not previously been reported in A-T
      patients. The present study reports the case of a 22-year-old man diagnosed with
      A-T at the age of 6 years who was referred to our Digestive Disease Unit with a
      three-year history of hyperlipidemia and liver test alterations. Core liver
      biopsy showed similar lesions to those observed in nonalcoholic steatohepatitis.
      Immunohistochemical staining disclosed the absence of ATM protein in hepatocyte
      nuclei. We suggest that the liver injury may be mainly attributable to the
      oxidative stress associated with ATM protein deficiency, although other factors
      may have made a contribution. We propose the inclusion of A-T among the causes of
      nonalcoholic steatohepatitis, which may respond to antioxidant therapy. 

PMID- 25374731
TI  - Symptomatic Secondary Selective IgM Immunodeficiency in Adult Man with
      Undiagnosed Celiac Disease.
AB  - Selective IgM immunodeficiency (SIgMID) is a heterogeneous disorder with no known
      genetic background and may occur as a primary or a secondary condition. Celiac
      disease has been reported in association with several humeral immunodeficiencies,
      including isolated severe selective IgA deficiency, panhypogammaglobulinemia, and
      isolated combined IgA and IgM deficiency. There are only few reported cases of
      pediatric and adult patients with SIgMID and celiac disease. In this paper, we
      describe an adult patient with a symptomatic secondary SIgMID associated with
      undiagnosed celiac disease, with a resolution of clinical symptoms of
      immunodeficiency and serum IgM normalization following a gluten-free diet. 

PMID- 25374732
TI  - Acute spontaneously resolving pulmonary vasculitis: a case report.
AB  - This is the first description that we are aware of describing the spontaneous
      resolution of an acute pulmonary vasculitis, possibly secondary to microscopic
      polyangiitis. Haemoptysis is a common symptom for patients presenting to primary
      and tertiary referral centres, and pulmonary vasculitis is one of a variety of
      aetiologies that should always be considered. The pulmonary vasculitides are
      difficult diagnostic and management problems. They are encumbered by a relative
      paucity of level 1 evidence addressing their diagnosis, classification, and
      treatment. This is therefore an important paper to publish because it adds to the
      global breadth of experience with this important clinical condition. 

PMID- 25374733
TI  - A rare case of prototheca algaemia in a patient with systemic lupus erythematosus
      and recent belimumab infusion.
AB  - Novel agents for the treatment of immune-mediated diseases such as systemic lupus
      erythematosus (SLE) have been increasingly used as an alternative to or in
      combination with conventional therapies. Belimumab, a human monoclonal antibody
      that inhibits B-cell activating factor (BAFF), has demonstrated efficacy in
      moderate-to-severe SLE with similar adverse effects when compared to other
      biologic agents and conventional SLE therapies. Here, we describe a woman with
      SLE and diabetes mellitus (DM) on immunosuppressive therapy for five years who
      was admitted to the hospital for pneumonia but had a complicated hospital course
      with multiple infections and, most notably, a nosocomial algaemia due to
      Prototheca wickerhamii, which was treated successfully with amphotericin B. She
      had recently received three belimumab infusions as an outpatient prior to
      admission to the hospital. To the best of our knowledge no cases of human
      protothecosis in patients receiving belimumab have been described in the English
      literature; however, unusual infections have to be considered in all patients
      undergoing immunosuppressive therapies who persist with fever despite
      conventional antimicrobials. 

PMID- 25374734
TI  - The Efficacy of Mizoribine (Inosine Monophosphate Dehydrogenase Inhibitor) for
      ANCA-Associated Vasculitis with Hepatitis B Virus Carrier.
AB  - A 42-year-old female who was an asymptomatic carrier of hepatitis B virus (HBV)
      was diagnosed with antineutrophil cytoplasm antibody- (ANCA-) associated
      vasculitis and was induced to remission with 30 mg/day prednisolone nine years
      ago. Four years ago, she suffered recurrence of ANCA-associated vasculitis and
      with 30 mg/day prednisolone was induced to remission. This time, laboratory data
      showed 3-fold increase in myeloperoxidase antineutrophil cytoplasmic antibody
      (MPO-ANCA) levels. Administration of 30 mg/day prednisolone was started. Three
      days later, she was admitted to our hospital suffering from fatigue. After
      admission, urinalysis showed glomerular hematuria. Despite administration of 30
      mg/day prednisolone, MPO-ANCA titer had been of high level, ranging from 42 to 83
      EU for 2.5 months. Furthermore, the adverse effects of steroid were seen. We
      decided the tapering of prednisolone (25 mg/day) and the start of mizoribine (4
      carbamoyl-1-beta-D-ribofuranosyl imidazolium-5-olate) administration. After
      mizoribine treatment, MPO-ANCA titer was decreased without any mizoribine-related
      adverse effects. Six months later, MPO-ANCA titer was decreased to normal levels
      and she was induced to clinical remission without reactivation of HBV. We
      describe the effectiveness of mizoribine for the ANCA-associated vasculitis
      complicated with HBV-carrier. 

PMID- 25374735
TI  - Intrapleural bortezomib for the therapy of myelomatous pleural effusion: a case
      report.
AB  - Myelomatous pleural effusion (MPE) is an extremely rare manifestation of multiple
      myeloma (MM). We present a case of MPE in a patient with IgG-kappa MM treated
      with intrapleural bortezomib with systemic bortezomib-based therapy. Although we
      observed good local response, the patient succumbed due to systemic myeloma
      progression. 

PMID- 25374736
TI  - Scalp necrosis as a late sign of giant-cell arteritis.
AB  - Retinal infarction and scalp necrosis are described as unusual but devastating
      complications of giant-cell arteritis. We report a patient with this rare
      complication and emphasize the importance of timely diagnosis and treatment of
      giant-cell arteritis. 

PMID- 25374737
TI  - Autoimmune Lymphoproliferative Syndrome and Epstein-Barr Virus-Associated
      Lymphoma: An Adjunctive Diagnostic Role for Monitoring EBV Viremia?
AB  - Background. Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder
      of lymphocyte homeostasis due to defects in FAS-mediated apoptosis. ALPS is
      characterized by childhood onset of chronic lymphadenopathy and splenomegaly,
      autoimmunity, an expanded population of double-negative T cells (DNTCs), and an
      increased risk of lymphoma. This propensity for lymphoma in ALPS is not well
      understood. It is possible that lymphomagenesis in some of these patients may
      result from Epstein-Barr virus (EBV) infection exploiting the defective T-cell
      surveillance resulting from impaired FAS-mediated apoptosis. Case Presentation.
      We report the first case, to our knowledge, of lymphoma in a patient with ALPS
      that was clinically heralded by progressively increasing EBV viremia. We discuss
      its practical implications and the possible immune pathways involved in the
      increased risk for EBV-associated lymphoproliferative disorders in ALPS patients.
      Conclusion. In patients with ALPS, distinguishing chronic lymphadenopathy from
      emerging lymphoma is difficult, with few practical recommendations available.
      This case illustrates that, at least for some patients, monitoring for
      progressively increasing EBV viremia may be useful. 

PMID- 25374738
TI  - Differentiation between Celiac Disease, Nonceliac Gluten Sensitivity, and Their
      Overlapping with Crohn's Disease: A Case Series.
AB  - Celiac disease (CD) and nonceliac gluten sensitivity (NCGS) are two distinct
      conditions triggered by the ingestion of gliadin. Although symptoms of nonceliac
      gluten sensitivity may resemble those of celiac disease, due to the lack of
      objective diagnostic tests, NCGS is associated with overlapping symptomatologies
      of autoimmunities and Crohn's disease. Furthermore, a gluten-free diet is only
      recommended for those who meet the criteria for a diagnosis of CD. Unfortunately,
      that leaves many nonceliac gluten-sensitive people suffering unnecessarily from
      very serious symptoms that put them at risk for complications of autoimmune
      disorders that might be resolved with a gluten-free diet. Thus, a new paradigm is
      needed for aid in diagnosing and distinguishing among various gut-related
      diseases, including CD, NCGS (also known as silent celiac disease), and gut
      related autoimmunities. Herein, we report three different cases: the first, an
      elderly patient with celiac disease which was diagnosed based on signs and
      symptoms of malabsorption and by a proper lab test; second, a case of NCGS which
      was initially misdiagnosed as lupus but was detected as NCGS by a proper lab test
      with its associated autoimmunities, including gluten ataxia and neuromyelitis
      optica; third, a patient with NCGS overlapping with Crohn's disease. The
      symptomatologies of all three patients improved significantly after 12 months of
      gluten-free diet plus other modalities. 

PMID- 25374739
TI  - A precocious cerebellar ataxia and frequent Fever episodes in a 16-month-old
      infant revealing ataxia-telangiectasia syndrome.
AB  - Ataxia-telangiectasia (AT) is the most frequent progressive cerebellar ataxia in
      infancy and childhood. Immunodeficiency which includes both cellular and humoral
      arms has variable severity. Since the clinical presentation is extremely
      variable, a high clinical suspicion will allow an early diagnosis. Serum alpha
      fetoprotein is elevated in 80-85% of patients and therefore could be used as a
      screening tool. Here, we present a case of a 5-year-old female infant who was
      admitted to our department at the age of 16 months because of gait disorders and
      febrile episodes that had begun at 5 months after the cessation of breastfeeding.
      Serum alfa-fetoprotein level was elevated. Other investigations showed
      leukocytopenia with lymphopenia, reduced IgG2 and IgA levels, and low titers of
      specific postimmunization antibodies against tetanus toxoid and Haemophilus B
      polysaccharide. Peripheral lymphocytes subsets showed reduction of T cells with a
      marked predominance of T cells with a memory phenotype and a corresponding
      reduction of naive T cells; NK cells were very increased (41%) with normal
      activity. The characterization of the ATM gene mutations revealed 2 specific
      mutations (c.5692C > T/c.7630-2A > C) compatible with AT diagnosis. It was
      concluded that AT syndrome should be considered in children with precocious signs
      of cerebellar ataxia and recurrent fever episodes. 

PMID- 25374740
TI  - Variant of X-Linked Chronic Granulomatous Disease Revealed by a Severe
      Burkholderia cepacia Invasive Infection in an Infant.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized
      by increased susceptibility to bacteria and fungi since early in life, caused by
      mutations in any of the five genes coding for protein subunits in NADPH oxidase.
      X-linked variant CGD can be missed during routine evaluation or present later in
      life due to hypomorphic mutations and a residual superoxide production. The case
      of a 10-month-old boy who died of pneumonia is reported. The isolation of
      Burkholderia cepacia from his lung, together with a marginally low nitroblue
      tetrazolium reduction assay (NBT), made us suspect and pursue the molecular
      diagnosis of CGD. A postmortem genetic analysis finally demonstrated CGD caused
      by a hypomorphic missense mutation with normal gp91 (phox) expression. In a
      patient being investigated for unusually severe or recurrent infection, a high
      index of suspicion of immunodeficiency must be maintained. 

PMID- 25374741
TI  - Rare cause of seizures, renal failure, and gangrene in an 83-year-old diabetic
      male.
AB  - We report an 83-year-old diabetic male who presented with acute-onset renal
      failure, seizures, psychosis, pneumonia, and right foot gangrene. Investigations
      revealed thrombocytopenia, CSF lymphocytosis, ANA and dsDNA positivity,
      hypocomplementemia, and pneumonitis following which he was treated with pulse
      methylprednisolone. He was treated for Pseudomonas-related ventilator-associated
      pneumonia, candiduria, and E. coli-related bedsore infection prior to discharge.
      He was discharged at request and died 17 days later due to a respiratory
      infection. 

PMID- 25374742
TI  - Lipoid pneumonia in a gas station attendant.
AB  - The exogenous lipoid pneumonia, uncommon in adults, is the result of the
      inhalation and/or aspiration of lipid material into the tracheobronchial tree.
      This is often confused with bacterial pneumonia and pulmonary tuberculosis due to
      a nonspecific clinical and radiologic picture. It presents acutely or chronically
      and may result in pulmonary fibrosis. We describe here a case of lipoid pneumonia
      in a gas station attendant who siphoned gasoline to fill motorcycles; he was
      hospitalized due to presenting with a respiratory infection that was hard to
      resolve. The patient underwent bronchoscopy with bronchoalveolar lavage, which,
      on cytochemical (oil red O) evaluation, was slightly positive for lipid material
      in the foamy cytoplasm of alveolar macrophages. Due to his occupational history
      and radiographic abnormalities suggestive of lipoid pneumonia, a lung biopsy was
      performed to confirm the diagnosis. The patient was serially treated with
      segmental lung lavage and showed clinical, functional, and radiological
      improvement. 

PMID- 25374743
TI  - Disseminated alveolar hydatid disease resembling a metastatic malignancy: a
      diagnostic challenge-a report of two cases.
AB  - Alveolar hydatid disease or alveolar echinococcosis is a disease of the parasite
      Echinococcus multilocularis that is potentially fatal if left untreated. It
      primarily involves the liver but can be disseminated to other organs like the
      lungs and the brain by hematogenous route. Multiorgan involvement and the
      aggressive appearance of lesions make alveolar hydatid disease easy to confuse
      with a metastatic malignancy. For this reason, histopathological confirmation is
      essential for definite diagnosis. We present the imaging features of this disease
      in two patients in order to emphasize that these lesions can be easily
      misdiagnosed as malignancies. 

PMID- 25374744
TI  - A case of continuous negative pressure wound therapy for abdominal infected
      lymphocele after kidney transplantation.
AB  - Lymphocele is a common complication after kidney transplantation. Although
      superinfection is a rare event, it generates a difficult management problem;
      generally, open surgical drainage is the preferred method of treatment but it may
      lead to complicated postoperative course and prolonged healing time. Negative
      pressure wound therapy showed promising outcomes in various surgical disciplines
      and settings. We present a case of an abdominal infected lymphocele after kidney
      transplantation managed with open surgery and negative pressure wound therapy. 

PMID- 25374745
TI  - Role of murine asthma model in discovering asthma susceptible genes.

PMID- 25374746
TI  - The effects of environmental toxins on allergic inflammation.
AB  - The prevalence of asthma and allergic disease has increased worldwide over the
      last few decades. Many common environmental factors are associated with this
      increase. Several theories have been proposed to account for this trend,
      especially those concerning the impact of environmental toxicants. The
      development of the immune system, particularly in the prenatal period, has far
      reaching consequences for health during early childhood, and throughout adult
      life. One underlying mechanism for the increased levels of allergic responses,
      secondary to exposure, appears to be an imbalance in the T-helper function caused
      by exposure to the toxicants. Exposure to environmental endocrine-disrupting
      chemicals can result in dramatic changes in cytokine production, the activity of
      the immune system, the overall Th1 and Th2 balance, and in mediators of type 1
      hypersensitivity mediators, such as IgE. Passive exposure to tobacco smoke is a
      common risk factor for wheezing and asthma in children. People living in urban
      areas and close to roads with a high volume of traffic, and high levels of diesel
      exhaust fumes, have the highest exposure to environmental compounds, and these
      people are strongly linked with type 1 hypersensitivity disorders and enhanced
      Th2 responses. These data are consistent with epidemiological research that has
      consistently detected increased incidences of allergies and asthma in people
      living in these locations. During recent decades more than 100,000 new chemicals
      have been used in common consumer products and are released into the everyday
      environment. Therefore, in this review, we discuss the environmental effects on
      allergies of indoor and outside exposure. 

PMID- 25374747
TI  - Diagnosis and management of immediate hypersensitivity reactions to
      cephalosporins.
AB  - Cephalosporins can cause a range of hypersensitivity reactions, including IgE
      mediated, immediate reactions. Cephalosporin allergy has been reported with use
      of a specific cephalosporin, as a cross-reaction between different cephalosporins
      or as a cross-reaction to other beta-lactam antibiotics. Unlike penicillins, the
      exact allergenic determinants of cephalosporins are less well understood and
      thus, standardized diagnostic skin testing is not available. Nevertheless, skin
      testing with diluted solutions of cephalosporins can be valuable in confirming
      IgE-mediated hypersensitivity reactions. In vitro tests are in development using
      recent technological advances and can be used as complementary tests. However,
      they are not commonly used because of their reduced sensitivity and limited
      availability. In selected cases of inconclusive results in both skin tests and
      IgE assays, a graded challenge or induction of drug tolerance with the implicated
      cephalosporin should be performed. 

PMID- 25374748
TI  - Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway
      Inflammation and Human Investigations.
AB  - PURPOSE: Based on a previous gene expression study in a mouse model of asthma, we
      selected 60 candidate genes and investigated their possible roles in human
      asthma. METHODS: In these candidate genes, 90 SNPs were genotyped using MassARRAY
      technology from 311 asthmatic children and 360 healthy controls of the Hungarian
      (Caucasian) population. Moreover, gene expression levels were measured by RT PCR
      in the induced sputum of 13 asthmatics and 10 control individuals. t-tests, chi
      square tests, and logistic regression were carried out in order to assess
      associations of SNP frequency and expression level with asthma. Permutation tests
      were performed to account for multiple hypothesis testing. RESULTS: The frequency
      of 4 SNPs in 2 genes differed significantly between asthmatic and control
      subjects: SNPs rs2240572, rs2240571, rs3735222 in gene SCIN, and rs32588 in gene
      PPARGC1B. Carriers of the minor alleles had reduced risk of asthma with an odds
      ratio of 0.64 (0.51-0.80; P=7*10(-5)) in SCIN and 0.56 (0.42-0.76; P=1.2*10(-4))
      in PPARGC1B. The expression levels of SCIN, PPARGC1B and ITLN1 genes were
      significantly lower in the sputum of asthmatics. CONCLUSIONS: Three potentially
      novel asthma-associated genes were identified based on mouse experiments and
      human studies.

PMID- 25374749
TI  - Reference ranges and determinant factors for exhaled nitric oxide in a healthy
      korean elderly population.
AB  - PURPOSE: Exhaled nitric oxide (NO) is a useful non-invasive biomarker for asthma
      diagnosis; however, the literature suggests that exhaled NO levels may be
      affected by demographic factors. The present analysis investigated determinant
      factors that present exhaled NO reference levels for Korean elderly adults.
      METHODS: For reference levels, we analyzed the baseline data of healthy adult
      participants in the Ansung cohort. The fraction of exhaled NO (FeNO) was measured
      by NIOX MINO(r). The characterization of the subjects was performed through
      structured questionnaires, spirometry, and methacholine challenge tests. To
      validate the diagnostic utility of the determined reference levels, asthma
      patients were recruited from medical institutions for FeNO measurement. RESULTS:
      A total of 570 healthy subjects were analyzed (mean age, 59.9+/-12.3; male,
      37.0%) for reference levels. FeNO levels significantly correlated with weight,
      height, body mass index, atopy, or forced expiratory volume in 1 second %
      predicted by simple linear regression analysis. Multiple linear regression
      analysis identified gender as an independent determinant for FeNO levels;
      subsequently, the reference values for FeNO were 18.2+/-10.6 ppb (5th to 95th
      percentile, 6.0 to 37.4 ppb) for males and 12.1+/-6.9 ppb (5th to 95th
      percentile, 2.5 to 27.0 ppb) for females. The diagnostic utility of FeNO
      reference levels was validated by receiver operating curve analysis (area under
      curve, 0.900 for males and 0.885 for females) for diagnosing asthma. The optimal
      cutoff values for the prediction of asthma were 30.5 ppb for males and 20.5 ppb
      for females. CONCLUSIONS: The current analysis presented reference ranges and the
      diagnostic utility of FeNO levels for asthma in Korean elderly adults.

PMID- 25374750
TI  - Food hypersensitivity in mexican adults at 18 to 50 years of age: a questionnaire
      survey.
AB  - PURPOSE: There is limited epidemiological evidence of food hypersensitivity (FH)
      in the adult population. We aimed to determine the prevalence of FH in Mexican
      adults, their clinical features and to establish common food involved in its
      appearance. METHODS: We designed a cross-sectional study using a fixed quota
      sampling; 1,126 subjects answered a structured survey to gather information
      related to FH. RESULTS: The prevalence of FH in adults was 16.7% (95% CI, 14.5%
      to 18.8%), without statistical significant differences related to gender (women,
      17.5% and men, 15.9%) or residential location. The most common clinical
      manifestations in adults with FH were oral allergy syndrome (70 of 1,126) and
      urticaria (55 of 1,126). According to category, fruits and vegetables were the
      most frequent foods to trigger FH (6.12%) and were individually related to shrimp
      (4.0%), and cow milk (1.5%). Adults under age 25 had a higher frequency of FH
      (OR, 1.39; 95% CI, 1.01 to 1.91, P <0.001). Personal history of any atopic
      disease was significantly associated with FH (P <0.0001). CONCLUSIONS: The
      prevalence of FH is relatively high in Mexican adults, and FH is significantly
      associated with atopic diseases.

PMID- 25374751
TI  - Relationship between indoor air pollutant levels and residential environment in
      children with atopic dermatitis.
AB  - PURPOSE: This study was aimed to investigate the relationship between indoor air
      pollutant levels and residential environment in children with atopic dermatitis
      (AD) living in Seoul. METHODS: A total of 150 children with AD were included.
      Residential environment was assessed by questionnaires which were completed by
      their parents. To evaluate the level of exposure to the indoor air pollutants,
      concentrations of the indoor air pollutants including particulate matter with
      diameter less than 10 um (PM10), formaldehyde, carbon dioxide (CO2), carbon
      monoxide (CO), nitrogen dioxide (NO2), Total Volatile Organic Compound (TVOC),
      benzene, toluene, ethyl-benzene, xylene, styrene, bacterial aerosols, and
      airborne fungi were measured. RESULTS: A significant difference was exhibited in
      the levels of PM10 in case of visible fungus on the walls (P=0.047). There was
      relationship between the construction year of the house, moving to a newly
      constructed building within 1 year and formaldehyde level. With the use of
      artificial air freshener, the differences were found in the concentrations of
      TVOC (P=0.003), benzene (P=0.015), toluene (P=0.012) and ethyl-benzene (P=0.027).
      The concentration of xylene was significantly high when oil was used as heating
      fuel (P=0.015). Styrene exhibited differences depending on building type and its
      concentrations were significantly high in a residential and commercial complex
      building (P=0.005). The indoor concentration of bacterial aerosols was
      significantly low with the use of air cleaner (P=0.045). High NO2, benzene
      concentrations were present in case of almost no ventilation (P=0.028 and
      P=0.028, respectively). CONCLUSIONS: Individual residential environments are
      closely related with the levels of the indoor air pollutants. To alleviate AD
      symptoms, simple questions about residential environments such as visible fungus
      on the walls and the use of artificial air freshener are helpful to assess the
      possibility of increased indoor air pollutant levels when direct measurement is
      not available.

PMID- 25374752
TI  - The Importance of Allergen Avoidance in High Risk Infants and Sensitized
      Patients: A Meta-analysis Study.
AB  - PURPOSE: At this time, there is uncertainty regarding whether allergen avoidance
      is the most appropriate strategy for managing or preventing allergies. The
      purpose of this study was to evaluate the effectiveness of allergen avoidance in
      the prevention of allergic symptoms in previously sensitized patients and
      newborns that have the potential to develop allergies. METHODS: We performed
      online searches of articles published from January 1980 to December 2012 in
      PubMed and The Cochrane Central Register of Controlled Trials, and selected
      articles involving randomized controlled trials (RCTs) and allergen avoidance.
      The parameters used to determine allergenic potential in newborns included the
      risk ratio (RR) of eczema, asthma, rhinitis, wheeze, and cough. The methods
      employed to evaluate previously sensitized patients were the standardized mean
      difference (SMD) of forced expiratory volume in 1 second (FEV1) and peak
      expiratory flow rate (PEFR). Data quality was assessed using the Jadad scale.
      RESULTS: A total of 14 RCTs were identified. Meta-analysis demonstrated that
      allergen avoidance for newborns did not reduce the subsequent incidence of
      allergic diseases (eczema, P=0.21; rhinitis, P=0.3; cough, P=0.1) but
      significantly reduced the incidence of asthma and wheezing in high-risk infants
      (asthma, P=0.03; wheeze, P=0.0004). However, previously sensitized patients who
      reduced their exposure to known allergens did not show improvement in their lung
      functions (FEV1, P=0.3; PEFR morning, P=0.53; PEFR evening, P=0.2; PEFR, P=0.29).
      CONCLUSIONS: Allergen avoidance may not always be successful in preventing
      allergic symptoms. However, rigorous methodological studies are required to
      confirm this hypothesis.

PMID- 25374753
TI  - Long-term Effects of Specific Allergen Immunotherapy Against House Dust Mites in
      Polysensitized Patients With Allergic Rhinitis.
AB  - PURPOSE: Allergen-specific immunotherapy is the only currently available
      treatment to modify the natural history of allergic rhinitis (AR). If patients
      are polysensitized, it is difficult to identify the allergen causing the allergic
      symptoms. We evaluated the effectiveness of immunotherapy against house dust
      mites (HDMs) in AR patients polysensitized to both HDMs and seasonal allergens.
      METHODS: Thirty AR patients polysensitized to both HDMs and seasonal allergens
      (group A) and 30 patients sensitized to HDMs only (group B) were enrolled in this
      study. All subjects who received immunotherapy against HDMs for more than 2 years
      were evaluated by the multiple allergen simultaneous test (MAST) to determine the
      specific IgE level in luminescence units, total eosinophil counts in peripheral
      blood, serum total IgE, total nasal symptom scores, and the rhinoconjunctivitis
      quality of life questionnaire (RQLQ) before and after immunotherapy. RESULTS:
      There were no statistical differences in levels of total and specific IgE, or
      total eosinophil count between the two groups. The total nasal symptom scores,
      RQLQ and medication scores significantly decreased after immunotherapy in both
      groups, however no significant differences were noted between the two groups.
      CONCLUSIONS: We determined that the primary causative allergen of AR in Seoul,
      Korea is perennial allergens, such as HDMs, rather than seasonal allergens. This
      study provides a reference for the selection of allergens to use in immunotherapy
      for polysensitized AR patients living in an urban environment.

PMID- 25374754
TI  - Development of a questionnaire for the assessment of quality of life in korean
      children with allergic rhinitis.
AB  - PURPOSE: Korean children have their own unique lifestyle based on their living
      environment and culture. This study aimed to develop a questionnaire to evaluate
      the quality of life in Korean children with allergic rhinitis. METHODS: After a
      preliminary survey, an initial questionnaire was developed. Questions were
      modified to be easily understood by young children aged 6 to 7 years. The
      modified questionnaire was tested on children aged 6 to 12 years old. Item
      scores, defined as the proportion of children whose answer score was 1 point or
      higher was multiplied by the average answer score of each question, were used to
      identify questions that have practical application to the quality of life in
      Korean children with allergic rhinitis. Differences in answer scores between
      children with allergic rhinitis and those who were healthy were assessed by a
      Wilcoxon rank-sum test. The relationship between nasal index scores and quality
      of life scores was determined by a Spearman rank order test. RESULTS: An initial
      questionnaire was composed of 21 items. We identified 19 questions with item
      scores above 0.5 in children with allergic rhinitis, many of which were related
      to nasal symptoms and 10 questions that were different between the allergic
      rhinitis group and the control group. The final questionnaire included the 10
      questions that had both high item scores and a significant difference in the
      answer scores between the two groups. CONCLUSIONS: The developed questionnaire is
      essential and practical for assessing discomfort related to the symptoms felt by
      Korean children with allergic rhinitis.

PMID- 25374755
TI  - Oral lovastatin attenuates airway inflammation and mucus secretion in ovalbumin
      induced murine model of asthma.
AB  - PURPOSE: Lovastatin is an effective inhibitor of cholesterol synthesis. A
      previous study demonstrated that lovastatin can also suppress airway
      hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the
      effect of lovastatin on mucus secretion and inflammation-associated gene
      expression in the lungs of murine model of asthma. METHODS: Female BALB/c mice
      were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection,
      and orally administered lovastatin from days 14 to 27 post-injection. Gene
      expression in lung tissues was analyzed using real-time polymerase chain
      reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human
      bronchial epithelial cells were used to evaluate the effect of lovastatin on the
      expression of cell adhesion molecules, chemokines, and proinflammatory cytokines
      in vitro. RESULTS: We showed that lovastatin inhibits the expression of Th2
      associated genes, including eotaxins and adhesion molecules, in the lungs of
      murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet
      cell hyperplasia were significantly decreased in the lung tissue of murine model
      of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and
      expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However,
      a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA
      levels in serum, and suppress the expression of Th2-associated cytokines in
      splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL
      6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein
      expression. Consistent with this, lovastatin also suppressed the ability of HL-60
      cells to adhere to inflammatory BEAS-2B cells. CONCLUSIONS: These data suggest
      that lovastatin suppresses mucus secretion and airway inflammation by inhibiting
      the production of eotaxins and Th2 cytokines in murine model of asthma.

PMID- 25374756
TI  - The Serine Protease Inhibitor, 4-(2-aminoethyl) Benzene Sulfonyl Fluoride
      Hydrochloride, Reduces Allergic Inflammation in a House Dust Mite Allergic
      Rhinitis Mouse Model.
AB  - PURPOSE: Serine protease inhibitors are involved in immune development, anti
      inflammatory mechanisms, and tissue repair. In the present study, the serine
      protease inhibitor 4-(2-aminoethyl) benzene sulfonyl fluoride hydrochloride
      (AEBSF) was evaluated for its prophylactic and therapeutic applications in a
      mouse model of allergic rhinitis (AR). METHODS: BALB/c mice were divided into 5
      groups: contol (CON), Dermatophagoides farinae (Derf), AR mice treated with AEBSF
      before sensitization (S), AR mice treated with AEBSF after challenge (C), and
      steroid groups. Derf was used as an allergen. AEBSF was administered before S or
      after C. Allergic symptom scores, eosinophil counts, proteolytic activity,
      interferon-gamma, interleukin (IL)-10 levels and serum Derf-specific IgE levels
      were measured. T-bet, GATA-3, Foxp3, IL-13, and transforming growth factor (TGF)
      beta mRNA levels were determined using real-time polymerase chain reaction.
      CD4(+)CD25(+)Foxp3(+) T cells were assessed using flow cytometry. RESULTS:
      Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, IL-13 mRNA
      levels, and tissue eosinophil counts decreased in both the S and C groups
      (P<0.05). Additionally, the percentage of CD4(+)CD25(+)Foxp3(+) T cells, IL-10
      levels, and Foxp3 mRNA levels increased in the S and C groups compared with those
      in the Derf group (P<0.05). AEBSF treatment decreased the proteolytic activity in
      the S and C groups (P<0.05). CONCLUSIONS: Prophylactic and therapeutic treatment
      with AEBSF significantly reduces allergic airway inflammation and can induce
      regulatory T cells in a murine model of AR.

PMID- 25374757
TI  - Histamine Promotes the Release of Interleukin-6 via the H1R/p38 and NF-kappaB
      Pathways in Nasal Fibroblasts.
AB  - PURPOSE: Based on the close relationship between histamine and interleukin 6 (IL
      6), we hypothesized that histamine may regulate the production of cytokines, such
      as IL-6, during allergic inflammation. Here, we examined the role of histamine in
      IL-6 production and histamine receptor activity in nasal fibroblasts, along with
      the mechanisms underlying these effects. METHODS: Experiments were performed
      using nasal fibroblasts from 8 normal patients. RT-PCR was used to identify the
      major histamine receptors expressed in nasal fibroblasts. Fibroblasts were then
      treated with histamine with or without histamine-receptor antagonists, and
      monitored for IL-6 production using an ELISA. Four potential downstream signaling
      molecules, p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal
      kinase (JNK), and NF-kappaB, were evaluated by Western blot, and a luciferase
      reporter assay. RESULTS: Elevated expression was seen for all histamine
      receptors, with IL-6 protein levels increasing significantly following histamine
      stimulation. Among the histamine-receptor specific antagonists, only the H1R
      antagonist significantly decreased IL-6 production in histamine-stimulated nasal
      fibroblasts. Histamine increased the expression level of phosphorylated p38
      (pp38), pERK, and pJNK, as well as NF-kappaB induction. The H1R antagonist
      actively suppressed pp38 and NF-kappaB expression in histamine-induced nasal
      fibroblasts, but not pERK and pJNK. The p38 inhibitor strongly attenuated IL-6
      production in histamine-stimulated nasal fibroblasts. CONCLUSIONS: The data
      presented here suggest that antihistamines may be involved in the regulation of
      cytokines, such as IL-6, due to the role of histamine as an inflammatory mediator
      in nasal fibroblasts.

PMID- 25374758
TI  - A case of chronic cough caused by achalasia misconceived as gastroesophageal
      reflux disease.
AB  - Cough is one of the most common symptoms that causes patients to seek outpatient
      medical care. If cough persists longer than 8 weeks, common causes of chronic
      cough, such as upper airway cough syndrome, asthma, and gastroesophageal reflux
      disease (GERD), should be considered. Although not a common cause of chronic
      cough, achalasia may cause symptoms very similar to reflux that can lead to its
      misdiagnosis as GERD. In this report, a 40-year-old woman presenting with chronic
      cough was initially diagnosed with GERD; however, her symptoms were refractory to
      conventional GERD treatment. Finally, she was diagnosed with achalasia. Her cough
      improved completely after pneumatic dilatation. Achalasia is a rare disease
      accompanied by dysphagia or regurgitation. If cough presumably due to GERD does
      not respond to treatment, or if the cause of chronic cough is uncertain,
      physicians should suspect achalasia. 

PMID- 25374759
TI  - Munchausen stridor-a strong false alarm of anaphylaxis.
AB  - The diagnosis of anaphylaxis is often based on reported symptoms which may not be
      accurate and lead to major psychosocial and financial impacts. We describe two
      adult patients who were diagnosed as having recurrent anaphylaxis witnessed by
      multiple physicians based on recurrent laryngeal symptoms. The claimed cause was
      foods in one and drugs in the other. We questioned the diagnosis because of
      absent documentation of objective findings to support anaphylaxis, and the
      symptoms occurred during skin testing though the test sites were not reactive.
      Our initial skin testing with placebos reproduced the symptoms without objective
      findings. Subsequent skin tests with the suspected allergens were negative yet
      reproduced the symptoms without objective findings. Disclosing the test results
      markedly displeased one patient but reassured the other who subsequently
      tolerated the suspected allergen. In conclusion, these 2 patients' symptoms and
      evaluation were not supportive of their initial diagnosis of recurrent
      anaphylaxis. The compatible diagnosis was Munchausen stridor which requires
      psychiatric evaluation and behavior modification, but often rejected by patients.

PMID- 25374760
TI  - Evaluation of gastrointestinal bleeding: Update of current radiologic strategies.
AB  - Gastrointestinal bleeding (GIB) is a common presentation with significant
      associated morbidity and mortality, the prevalence of which continues to rise
      with the ever-increasing aging population. Initial evaluation includes an
      esophagoduodeonscopy and/or colonoscopy, which may fail to reveal a source. Such
      cases prove to be a dilemma and require collaboration between gastroenterology
      and radiology in deciding the most appropriate approach. Recently, there have
      been a number of radiologic advances in the approach to GIB. The purpose of this
      review is to provide an evidence-based update on the most current radiologic
      modalities available and an algorithmic approach to GIB. 

PMID- 25374762
TI  - Religiousness, Physical Activity and Obesity among Older Cancer Survivors:
      Results from the Health and Retirement Study 2000-2010.
AB  - The health behaviors of cancer survivors are an important research agenda in
      light of mounting evidence that aspects of health such as diet and exercise have
      salutary effects both mentally and physically for cancer survivors, a rapidly
      growing population in the United States and elsewhere. This paper analyzes data
      from the Health and Retirement Study 2000-2010 to determine if religious salience
      impacts the likelihood of obesity, changes in body mass index, and weekly
      vigorous activity. Two theories propose different hypotheses about the
      relationship. The health belief model would suggest the more religious may have
      the perception that healthy behaviors are positive and will be more likely to
      have a healthy body weight and get exercise. Conversely, high religious salience
      may signify a God locus of health control, leading to lesser likelihood of
      engagement in preventive health behaviors. Using logistic and regression analysis
      controlling for health behaviors at baseline (2000), these theories are tested,
      in addition to the explanatory power of lifestyle as a potential mechanism in the
      relationship of religiousness to body weight. Results show that high levels of
      religious salience may correspond to greater likelihood of obesity and lesser
      likelihood of getting regular exercise. Policy implications may include a greater
      emphasis on diet and physical activity in religious settings that may instead
      stress other health behaviors such as abstinence from smoking and alcohol.

PMID- 25374761
TI  - Protein kinases are potential targets to treat inflammatory bowel disease.
AB  - Protein kinases play a crucial role in the pathogenesis of inflammatory bowel
      disease (IBD), the two main forms of which are ulcerative colitis and Crohn's
      disease. In this article, we will review the mechanisms of involvement of protein
      kinases in the pathogenesis of and intervention against IBD, in terms of their
      effects on genetics, microbiota, mucous layer and tight junction, and the
      potential of protein kinases as therapeutic targets against IBD. 

PMID- 25374763
TI  - Utilization of Multiphoton Imaging For Real-Time Fate Determination of
      Mesenchymal Stem Cells in an Immunocompetent Mouse Model.
AB  - The clinical application of Mesenchymal Stem Cells (MSCs) for the treatment of a
      variety of diseases is the focus of intense research. Despite large research
      efforts many questions regarding MSC biology in vivo remain unanswered. For
      instance, we do not know for certain whether MSCs exert their therapeutic effects
      directly within the target tissue or indirectly by influencing the polarization
      of other cell types, such as macrophages, which can then home to the target
      tissue microenvironment. To help address this issue, the application of
      intravital multiphoton microscopy allows for the determination of the dynamic
      action of intact MSCs versus endogenous host cells at the target tissue site in
      real time.

PMID- 25374764
TI  - Neuroacanthocytosis in china: a review of published reports.
AB  - BACKGROUND: Neuroacanthocytosis (NA) syndromes are a group of rare diseases
      characterized by the presence of acanthocytes and neuronal multisystem pathology,
      including chorea-acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington's
      disease-like 2 (HDL-2), and pantothenate kinase-associated neurodegeneration
      (PKAN). China has the largest population in the world, which makes it a good
      location for investigating rare diseases like NA. METHODS: We searched Medline,
      ISI Proceedings, China National Knowledge Infrastructure, and Wanfang Data for
      literature published through December 31, 2013 for all the published Chinese NA
      case reports and extracted the clinical and laboratory findings. RESULTS: A total
      of 42 studies describing 66 cases were found to be eligible for inclusion. Age of
      symptom onset ranged from 5 to 74 years. The most common findings included
      hyperkinetic movements (88%), orofacial dyskinesia (80%), dystonia (67%), and
      dysarthria (68%), as well as caudate atrophy or enlarged lateral ventricles on
      neuroimaging (64%), and elevated creatine kinase (52%). Most cases were not
      confirmed by any specific molecular tests. Only two cases were genetically
      studied and diagnosed as ChAc or MLS. DISCUSSION: In view of the prevalence of NA
      syndromes in other countries, the number of patients in China appears to be
      underestimated. Chinese NA patients may benefit from the establishment of
      networks that offer specific diagnoses and care for rare diseases.

PMID- 25374766
TI  - Sudden onset of oromandibular dystonia after cerebellar stroke.
AB  - BACKGROUND: We present the case of a 65-year-old female with sudden-onset
      involuntary mouth opening, deviation of the jaw, facial grimacing, and tongue
      movements that started 6 months prior to her admission. CASE REPORT: She was
      diagnosed with oromandibular dystonia. Differential diagnosis of oromandibular
      dystonia and various etiologies were investigated. Neuroimaging studies revealed
      a left cerebellar infarction. DISCUSSION: To our knowledge, this case is the
      first oromandibular dystonia presenting with cerebellar ischemic stroke. Possible
      roles of the cerebellum for the pathophysiology of oromandibular dystonia are
      discussed.

PMID- 25374765
TI  - Evaluating Familial Essential Tremor with Novel Genetic Approaches: Is it a
      Genotyping or Phenotyping Issue?
AB  - BACKGROUND: Essential tremor is a common movement disorder with a strong
      heritable component. Large families with inherited forms of essential tremor have
      undergone genetic analyses by different approaches. However, our knowledge of
      genetic variants unequivocally linked to essential tremor is remarkably limited.
      Several explanations have been put forth to explain this challenge, including the
      possibility of mutations in non-coding areas of the genome. METHODS: We
      encountered a family with highly penetrant, autosomal dominant tremor. We
      hypothesized that, if a single coding gene mutation was responsible for the
      phenotype, novel genetic tools would allow us to identify it. We employed single
      nucleotide polymorphism (SNP) arrays in 17 members of this family followed by
      next generation whole-exome sequencing in five affected subjects. RESULTS: We did
      not identify any copy number variant or mutation that segregated with the disease
      phenotype. DISCUSSION: This study emphasizes the remarkably challenging field of
      tremor genetics and indicates that future studies should perhaps shift to
      analysis of the non-coding genome.

PMID- 25374767
TI  - Head and Arm Tremor in X-linked Spinal and Bulbar Muscular Atrophy.
AB  - BACKGROUND: X-linked spinal and bulbar muscular atrophy (SBMA) is a rare adult
      onset neuronopathy. Although tremor is known to occur in this disease, the number
      of reported cases of SBMA with tremor is rare, and the number with videotaped
      documentation is exceedingly rare. Our aim was to describe/document the
      characteristic signs of tremor in spinal and bulbar muscular atrophy. CASE
      REPORT: We report a case of a 58-year-old male with a positive family history of
      tremor. On examination, the patient had jaw and hand tremors but he also
      exhibited gynecomastia, progressive bulbar paresis, and wasting and weakness
      primarily in the proximal limb muscles. The laboratory tests revealed an elevated
      creatine phosphokinase. Genetic testing was positive for X-SBMA, with 42 CAG
      repeats. DISCUSSION: Essential tremor is one of the most common movement
      disorders, yet it is important for clinicians to be aware of the presence of
      other distinguishing features that point to alternative diagnoses. The presence
      of action tremor associated with muscle atrophy and gynecomastia should lead to a
      suspicion of SBMA.

PMID- 25374769
TI  - The "tremor diary": a useful tool in the management of patients with tremor.

PMID- 25374768
TI  - Tardive Syndromes are Rarely Reversible after Discontinuing Dopamine Receptor
      Blocking Agents: Experience from a University-based Movement Disorder Clinic.
AB  - BACKGROUND: Several studies have examined reversibility of tardive syndromes
      (TS), primarily in psychotic patients who are maintained on dopamine receptor
      blocking drugs. The results have varied widely. However, few have assessed
      remission rates after discontinuing the offending agents. This study evaluated
      reversibility of TS in patients who permanently withdrew the causative agent(s).
      We also examined for any possible clinical predictors of reversibility. METHODS:
      A retrospective cohort of 108 TS patients was studied. Most of the patients were
      not psychotic; most patients were being treated either for a mood disorder with
      atypical antipsychotics or for a gastrointestinal disturbance with
      metoclopramide. Patients were stratified on the basis of reversibility, and
      statistical tests were used for subgroup comparisons of relevant clinical
      variables. Logistic regression was undertaken to identify clinical variables
      predictive of reversibility. RESULTS: Only 13% of the cohort experienced
      reversibility of the TS, 2% without medical intervention. When stratified by
      reversibility, there were no significant differences in any study variables
      between subgroups. None of the study variables predicted reversibility in the
      logistic regression. DISCUSSION: Our study demonstrated a low remission rate for
      TS in a cohort of psychiatric and non-psychiatric patients seen in a movement
      disorder clinic after the offending agents were completely withdrawn. Such a
      finding has significant prognostic implications. It is possible that limitations
      of the retrospective design may have resulted in an underestimation. There is a
      clear need for prospective, multicenter, clinical trials in populations that can
      be safely withdrawn from dopamine receptor blocking agents so that true remission
      rates can be measured.

PMID- 25374770
TI  - The Test-Retest Reliability of the Photopic Negative Response (PhNR).
AB  - PURPOSE: The photopic negative response (PhNR) may be useful as a tool to monitor
      longitudinal change in retinal ganglion cell (RGC) function. The goal was to
      assess PhNR test-retest reliability, and to estimate the amount of change between
      tests that is likely to be statistically significant for an individual test
      subject. METHODS: Photopic electroretinograms (ERGs) were recorded from 49
      visually normal subjects (mean age, 38.9 years; range, 21-72 years). Signals were
      acquired using Dawson-Trick-Litzkow (DTL) electrodes in response to red stimulus
      at four flash energies (0.5, 1, 2.25, 3 cd.s/m2) on a blue background (10 cd/m2).
      The PhNR amplitude was recorded from prestimulus baseline to trough (BT),
      prestimulus baseline to fixed time point (BF), and b-wave peak to trough (PT).
      The ratio of baseline PhNR to b-wave amplitude (BT/b-wave) was calculated.
      Reliability was assessed using the intraclass correlation coefficient (ICC2,1)
      and coefficient of repeatability (CoR). RESULTS: Flash energy of 1.00 cd.s/m2
      produced reliable, well-defined traces. At this stimulus, the a- and b-wave
      amplitudes were reproduced with moderate reliability (ICC, 0.62; CoR%, 90.0%; and
      ICC, 0.74; CoR%, 54.3%; respectively). For PhNR, the order from most to least
      reliable measurement was: PT (ICC, 0.64; CoR%, 59.1%), BT (ICC, 0.40; CoR%,
      148.3%), and BF (ICC, 0.22; CoR%, 166.1%). The BT/b-wave did not improve
      reliability (ICC, 0.37; CoR%, 181.5). CONCLUSION: The b-wave peak-to-PhNR trough
      amplitude produced the most reliable measurement. TRANSLATIONAL RELEVANCE: A
      relatively large magnitude of change in PhNR amplitude is required to make
      clinical inferences about changes in RGC function. Refinement to the technique of
      acquisition and/or processing of the PhNR is recommended to improve reliability.

PMID- 25374771
TI  - Homonymous Visual Field Loss and Its Impact on Visual Exploration: A Supermarket
      Study.
AB  - PURPOSE: Homonymous visual field defects (HVFDs) may critically interfere with
      quality of life. The aim of this study was to assess the impact of HVFDs on a
      supermarket search task and to investigate the influence of visual search on task
      performance. METHODS: Ten patients with HVFDs (four with a right-sided [HR] and
      six with a left-sided defect [HL]), and 10 healthy-sighted, sex-, and age-matched
      control subjects were asked to collect 20 products placed on two supermarket
      shelves as quickly as possible. Task performance was rated as "passed" or
      "failed" with regard to the time per correctly collected item (TC -failed = 4.84
      seconds based on the performance of healthy subjects). Eye movements were
      analyzed regarding the horizontal gaze activity, glance frequency, and glance
      proportion for different VF areas. RESULTS: Seven of 10 HVFD patients (three HR,
      four HL) passed the supermarket search task. Patients who passed needed
      significantly less time per correctly collected item and looked more frequently
      toward the VFD area than patients who failed. HL patients who passed the test
      showed a higher percentage of glances beyond the 60 degrees  VF (P < 0.05).
      CONCLUSION: A considerable number of HVFD patients performed successfully and
      could compensate for the HVFD by shifting the gaze toward the peripheral VF and
      the VFD area. TRANSLATIONAL RELEVANCE: These findings provide new insights on
      gaze adaptations in patients with HVFDs during activities of daily living and
      will enhance the design and development of realistic examination tools for use in
      the clinical setting to improve daily functioning.
      (http://www.clinicaltrials.gov, NCT01372319, NCT01372332).

PMID- 25374772
TI  - Laser Activated Flow Regulator for Glaucoma Drainage Devices.
AB  - PURPOSE: To assess the capabilities of a new glaucoma drainage device regulator
      in controlling fluid flow as well as to demonstrate that this effect may be
      titratable by noninvasive means. METHODS: A rigid eye model with two main ports
      was used. On the first port, we placed a saline solution column. On the second,
      we placed a glaucoma shunt. We then measured the flow and flow rate through the
      system. After placing the regulator device on the tip of the tube, we measured
      again with the intact membrane and with the membrane open 50% and 100%. For the
      ex vivo testing we used a similar setting, using a cadaveric porcine eye, we
      measured again the flow and flow rate. However, this time we opened the membrane
      gradually using laser shots. A one-way analysis of variance and a Fisher's Least
      Significant Difference test were used for statistical significance. We also
      calculated the correlation between the numbers of laser shots applied and the
      main outcomes. RESULTS: The flow through the system with the glaucoma drainage
      device regulator (membrane intact and 50% open) was statistically lower than with
      the membrane open 100% and without device (P < 0.05). The flow was successfully
      controlled by the number of laser shots applied, and showed a positive
      correlation (+ 0.9). The flow rate was almost doubled every 10 shots and
      statistically lower than without device at all time (P < 0.05). CONCLUSIONS: The
      glaucoma drainage device regulator can be controlled noninvasively with laser,
      and allows titratable control of aqueous flow. TRANSLATIONAL RELEVANCE: Initial
      results and evidence from this experiment will justify the initiation of in vivo
      animal trials with the glaucoma drainage device regulator; which brings us closer
      to possible human trials and the chance to significantly improve the existing
      technology to treat glaucoma surgically.

PMID- 25374773
TI  - Relationship Between Optic Nerve Appearance and Retinal Nerve Fiber Layer
      Thickness as Explored with Spectral Domain Optical Coherence Tomography.
AB  - PURPOSE: To study the relationship between the appearance of the optic nerve and
      the retinal nerve fiber layer (RNFL) thickness determined by spectral domain
      optical coherence tomography (OCT). METHODS: Records from patients with spectral
      domain-OCT imaging in a neuro-ophthalmology practice were reviewed. Eyes with
      glaucoma/glaucoma suspicion, macular/optic nerve edema, pseudophakia, and with
      refractive errors > 6D were excluded. Optic nerve appearance by slit lamp
      biomicroscopy was related to the RNFL thickness by spectral domain-OCT and to
      visual field results. RESULTS: Ninety-one patients (176 eyes; mean age: 49 +/- 15
      years) were included. Eighty-three eyes (47%) showed optic nerve pallor; 89 eyes
      (50.6%) showed RNFL thinning (sectoral or average peripapillary). Average
      peripapillary RNFL thickness in eyes with pallor (mean +/- SD = 76 +/- 17 MUm)
      was thinner compared to eyes without pallor (91 +/- 14 MUm, P < 0.001). Optic
      nerve pallor predicted RNFL thinning with a sensitivity of 69% and a specificity
      of 75%. Optic nerve appearance predicted RNFL thinning (with a sensitivity and
      specificity of 81%) when RNFL had thinned by ~ 40%. Most patients with pallor had
      RNFL thinning with (66%) or without (25%) visual field loss; the remainder had
      normal RNFL and fields (5%) or with visual field abnormalities (4%). CONCLUSIONS:
      Optic nerve pallor as a predictor of RNFL thinning showed fair sensitivity and
      specificity, although it is optimally sensitive/specific only when substantial
      RNFL loss has occurred. TRANSLATIONAL RELEVANCE: Finding an acceptable
      relationship between the optic nerve appearance by ophthalmoscopy and spectral
      domain-OCT RNFL measures will help the clinician's interpretation of the
      information provided by this technology, which is gaining momentum in neuro
      ophthalmic research.

PMID- 25374774
TI  - Noninvasive analysis of metabolic changes following nutrient input into diverse
      fish species, as investigated by metabolic and microbial profiling approaches.
AB  - An NMR-based metabolomic approach in aquatic ecosystems is valuable for studying
      the environmental effects of pharmaceuticals and other chemicals on fish. This
      technique has also contributed to new information in numerous research areas,
      such as basic physiology and development, disease, and water pollution. We
      evaluated the microbial diversity in various fish species collected from Japan's
      coastal waters using next-generation sequencing, followed by evaluation of the
      effects of feed type on co-metabolic modulations in fish-microbial symbiotic
      ecosystems in laboratory-scale experiments. Intestinal bacteria of fish in their
      natural environment were characterized (using 16S rRNA genes) for trophic level
      using pyrosequencing and noninvasive sampling procedures developed to study the
      metabolism of intestinal symbiotic ecosystems in fish reared in their
      environment. Metabolites in feces were compared, and intestinal contents and feed
      were annotated based on HSQC and TOCSY using SpinAssign and network analysis.
      Feces were characterized by species and varied greatly depending on the feeding
      types. In addition, feces samples demonstrated a response to changes in the time
      series of feeding. The potential of this approach as a non-invasive inspection
      technique in aquaculture is suggested. 

PMID- 25374775
TI  - Network based meta-analysis prediction of microenvironmental relays involved in
      stemness of human embryonic stem cells.
AB  - Background. Human embryonic stem cells (hESCs) are pluripotent cells derived from
      the inner cell mass of in vitro fertilised blastocysts, which can either be
      maintained in an undifferentiated state or committed into lineages under
      determined culture conditions. These cells offer great potential for regenerative
      medicine, but at present, little is known about the mechanisms that regulate hESC
      stemness; in particular, the role of cell-cell and cell-extracellular matrix
      interactions remain relatively unexplored. Methods and Results. In this study we
      have performed an in silico analysis of cell-microenvironment interactions to
      identify novel proteins that may be responsible for the maintenance of hESC
      stemness. A hESC transcriptome of 8,934 mRNAs was assembled using a meta-analysis
      approach combining the analysis of microarrays and the use of databases for
      annotation. The STRING database was utilised to construct a protein-protein
      interaction network focused on extracellular and transcription factor components
      contained within the assembled transcriptome. This interactome was structurally
      studied and filtered to identify a short list of 92 candidate proteins, which may
      regulate hESC stemness. Conclusion. We hypothesise that this list of proteins,
      either connecting extracellular components with transcriptional networks, or with
      hub or bottleneck properties, may contain proteins likely to be involved in
      determining stemness. 

PMID- 25374776
TI  - X-ray Synchrotron Microtomography of a silicified Jurassic Cheirolepidiaceae
      (Conifer) cone: histology and morphology of Pararaucaria collinsonae sp. nov.
AB  - We document a new species of ovulate cone (Pararaucaria collinsonae) on the basis
      of silicified fossils from the Late Jurassic Purbeck Limestone Group of southern
      England (Tithonian Stage: ca. 145 million years). Our description principally
      relies on the anatomy of the ovuliferous scales, revealed through X-ray
      synchrotron microtomography (SRXMT) performed at the Diamond Light Source (UK).
      This study represents the first application of SRXMT to macro-scale silicified
      plant fossils, and demonstrates the significant advantages of this approach,
      which can resolve cellular structure over lab-based X-ray computed
      microtomography (XMT). The method enabled us to characterize tissues and
      precisely demarcate their boundaries, elucidating organ shape, and thus allowing
      an accurate assessment of affinities. The cones are broadly spherical (ca. 1.3 cm
      diameter), and are structured around a central axis with helically arranged
      bract/scale complexes, each of which bares a single ovule. A three-lobed
      ovuliferous scale and ovules enclosed within pocket-forming tissue, demonstrate
      an affinity with Cheirolepidiaceae. Details of vascular sclerenchyma bundles,
      integument structure, and the number and attachment of the ovules indicate
      greatest similarity to P. patagonica and P. carrii. This fossil develops our
      understanding of the dominant tree element of the Purbeck Fossil Forest,
      providing the first evidence for ovulate cheirolepidiaceous cones in Europe.
      Alongside recent discoveries in North America, this significantly extends the
      known palaeogeographic range of Pararaucaria, supporting a mid-palaeolatitudinal
      distribution in both Gondwana and Laurasia during the Late Jurassic.
      Palaeoclimatic interpretations derived from contemporaneous floras, climate
      sensitive sediments, and general circulation climate models indicate that
      Pararaucaria was a constituent of low diversity floras in semi-arid Mediterranean
      type environments. 

PMID- 25374777
TI  - Chicks change their pecking behaviour towards stationary and mobile food sources
      over the first 12 weeks of life: improvement and discontinuities.
AB  - Chicks (Gallus gallus domesticus) learn to peck soon after hatching and then peck
      in rapid bursts or bouts with intervals of non-pecking activity. The food sources
      may be static such as seeds and chick crumb, or mobile such as a mealworm. Here,
      changes with age in pecking toward chick crumb and a mealworm were measured.
      Chicks were reared in pairs and their pecking of crumb food was video recorded in
      their pair housed environment, from food presentation, every third day from day 8
      (wk 2) to day 65 (wk 10). Peck rate at crumb food reached maximum levels at day
      32 (wk 5), and then declined, fitting a quadratic model, with no sex, sex of
      cagemate, or box order effects. Within bouts the peck rate was higher and it
      increased to day 41 (wk 6) and then declined, and here males pecked faster than
      females. A change in dietary protein concentration from 22% to 18% at day 28 (wk
      4) had no effect on subsequent peck rate. Pecking at and consumption of a
      mealworm in pair housed chicks were measured weekly from wks [5 to 12]. The
      latency to first worm peck and latency to swallow decreased to wk 8 and increased
      thereafter. The peck rate to first wormpeck and number of pecks to swallow
      increased to wk 8 and then declined paralleling the changes with crumb food. The
      increase in peck rate is coupled with an increase in efficiency in worm catching.
      The results are consistent with the view that the improvement in pecking ability
      and accuracy compliments change in nutritional requirement best served by an
      invertebrate food (IF) source requiring speed to achieve feeding success,
      especially with live prey. When this food source is no longer crucial these
      associated skill levels decline. An appreciation of the role of domestic fowl in
      controlling insect populations, at farm level, that are often vectors in disease
      spread is lacking. 

PMID- 25374778
TI  - The link between immunity and life history traits in scleractinian corals.
AB  - Immunity is an important biological trait that influences the survival of
      individuals and the fitness of a species. Immune defenses are costly and likely
      compete for energy with other life-history traits, such as reproduction and
      growth, affecting the overall fitness of a species. Competition among these
      traits in scleractinian corals could influence the dynamics and structural
      integrity of coral reef communities. Due to variability in biological traits
      within populations and across species, it is likely that coral colonies within
      population/species adjust their immune system to the available resources. In
      corals, the innate immune system is composed of various pathways. The immune
      system components can be assessed in the absence (constitutive levels) and/or
      presence of stressors/pathogens (immune response). Comparisons of the
      constitutive levels of three immune pathways (melanin synthesis, antioxidant and
      antimicrobial) of closely related species of Scleractinian corals allowed to
      determine the link between immunity and reproduction and colony growth. First, we
      explored differences in constitutive immunity among closely related coral species
      of the genus Meandrina with different reproductive patterns (gonochoric vs.
      hermaphrodite). We then compared fast-growing branching vs. slow-growing massive
      Porites to test co-variation between constitutive immunity and growth rates and
      morphology in corals. Results indicate that there seems to be a relationship
      between constitutive immunity and sexual pattern with gonochoric species showing
      significantly higher levels of immunity than hermaphrodites. Therefore,
      gonochoric species maybe better suited to resist infections and overcome
      stressors. Constitutive immunity varied in relation with growth rates and colony
      morphology, but each species showed contrasting trends within the studied immune
      pathways. Fast-growing branching species appear to invest more in relatively low
      cost pathways of the immune system than slow-growing massive species. In corals,
      energetic investments in life-history traits such as reproduction and growth rate
      (higher energy investment) seem to have a significant impact on their capacity to
      respond to stressors, including infectious diseases and coral bleaching. These
      differences in energy investment are critical in the light of the recent
      environmental challenges linked to global climate change affecting these
      organisms. Understanding physiological trade-offs, especially those involving the
      immune system, will improve our understanding as to how corals could/will respond
      and survive in future adverse environmental conditions associated with climate
      change. 

PMID- 25374779
TI  - Purification and properties of glyceraldehyde-3-phosphate dehydrogenase from the
      skeletal muscle of the hibernating ground squirrel, Ictidomys tridecemlineatus.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the skeletal muscle of
      euthermic and torpid Ictidomys tridecemlineatus was purified to electrophoretic
      homogeneity using a novel method involving Blue-agarose and Phenyl-agarose
      chromatography. Kinetic analysis of the enzymes isolated from the two conditions
      suggested the existence of two structurally distinct proteins, with GAPDH V max
      being 40-60% less for the enzyme from the torpid condition (in both glycolytic
      and gluconeogenic directions) as compared to the euthermic enzyme form. Thermal
      denaturation, in part determined by differential scanning fluorimetry, revealed
      that purified GAPDH from the torpid animals was significantly more stable that
      the enzyme from the euthermic condition. Mass spectrometry combined with Western
      blot analyses of purified GAPDH indicate that the cellular GAPDH population is
      extensively modified, with posttranslational phosphorylation, acetylation and
      methylation being detected. Global reduction in GAPDH tyrosine phosphorylation
      during torpor as well as site specific alterations in methylation sites suggests
      that that the stable changes observed in kinetic and structural GAPDH properties
      may be due to posttranslational modification of this enzyme during torpor. Taken
      together, these results suggest a stable suppression of GAPDH (possibly by some
      reversible posttranslational modification) during ground squirrel torpor, which
      likely contributes to the overall reduction in carbohydrate metabolism when these
      animals switch to lipid fuels during dormancy. 

PMID- 25374780
TI  - Elaborate cellulosome architecture of Acetivibrio cellulolyticus revealed by
      selective screening of cohesin-dockerin interactions.
AB  - Cellulosic waste represents a significant and underutilized carbon source for the
      biofuel industry. Owing to the recalcitrance of crystalline cellulose to
      enzymatic degradation, it is necessary to design economical methods of liberating
      the fermentable sugars required for bioethanol production. One route towards
      unlocking the potential of cellulosic waste lies in a highly complex class of
      molecular machines, the cellulosomes. Secreted mainly by anaerobic bacteria,
      cellulosomes are structurally diverse, cell surface-bound protein assemblies that
      can contain dozens of catalytic components. The key feature of the cellulosome is
      its modularity, facilitated by the ultra-high affinity cohesin-dockerin
      interaction. Due to the enormous number of cohesin and dockerin modules found in
      a typical cellulolytic organism, a major bottleneck in understanding the biology
      of cellulosomics is the purification of each cohesin- and dockerin-containing
      component, prior to analyses of their interaction. As opposed to previous
      approaches, the present study utilized proteins contained in unpurified whole
      cell extracts. This strategy was made possible due to an experimental design that
      allowed for the relevant proteins to be "purified" via targeted affinity
      interactions as a function of the binding assay. The approach thus represents a
      new strategy, appropriate for future medium- to high-throughput screening of
      whole genomes, to determine the interactions between cohesins and dockerins. We
      have selected the cellulosome of Acetivibrio cellulolyticus for this work due to
      its exceptionally complex cellulosome systems and intriguing diversity of its
      cellulosomal modular components. Containing 41 cohesins and 143 dockerins, A.
      cellulolyticus has one of the largest number of potential cohesin-dockerin
      interactions of any organism, and contains unusual and novel cellulosomal
      features. We have surveyed a representative library of cohesin and dockerin
      modules spanning the cellulosome's total cohesin and dockerin sequence diversity,
      emphasizing the testing of unusual and previously-unknown protein modules. The
      screen revealed several novel cell-bound cellulosome architectures, thus
      expanding on those previously known, as well as soluble cellulose systems that
      are not bound to the bacterial cell surface. This study sets the stage for
      screening the entire complement of cellulosomal components from A. cellulolyticus
      and other organisms with large cellulosome systems. The knowledge gained by such
      efforts brings us closer to understanding the exceptional catalytic abilities of
      cellulosomes and will allow the use of novel cellulosomal components in
      artificial assemblies and in enzyme cocktails for sustainable energy-related
      research programs. 

PMID- 25374781
TI  - What did you choose just now? Chimpanzees' short-term retention of memories of
      their own behavior.
AB  - Many recent comparative studies have addressed "episodic" memory in nonhuman
      animals, suggesting that birds, rodents, great apes, and others can remember
      their own behavior after at least a half-day delay. By contrast, despite numerous
      studies regarding long-term memory, few comparable studies have been conducted on
      short-term retention for own behavior. In the current study, we addressed the
      following question: Do chimpanzees remember what they have just done? Four
      chimpanzees performed matching-to-sample and visual search tasks on a routine
      basis and were occasionally (every four sessions) given a "recognition" test
      immediately after their response during visual search trials. Even though these
      test trials were given very rarely, all four chimpanzees chose the stimulus they
      selected in the visual search trials immediately before the test trial
      significantly more frequently than they chose the stimulus they selected in
      another distractor trial. Subsequent experiments ruled out the possibility that
      preferences for the specific stimuli accounted for the recognition test results.
      Thus, chimpanzees remembered their own behavior even within a short-term
      interval. This type of memory may involve the transfer of episodic information
      from working memory to long-term episodic-like memory (i.e., an episodic buffer).

PMID- 25374782
TI  - Associating disease-related genetic variants in intergenic regions to the genes
      they impact.
AB  - We present a method to assist in interpretation of the functional impact of
      intergenic disease-associated SNPs that is not limited to search strategies
      proximal to the SNP. The method builds on two sources of external knowledge: the
      growing understanding of three-dimensional spatial relationships in the genome,
      and the substantial repository of information about relationships among genetic
      variants, genes, and diseases captured in the published biomedical literature. We
      integrate chromatin conformation capture data (HiC) with literature support to
      rank putative target genes of intergenic disease-associated SNPs. We demonstrate
      that this hybrid method outperforms a genomic distance baseline on a small test
      set of expression quantitative trait loci, as well as either method individually.
      In addition, we show the potential for this method to uncover relationships
      between intergenic SNPs and target genes across chromosomes. With more extensive
      chromatin conformation capture data becoming readily available, this method
      provides a way forward towards functional interpretation of SNPs in the context
      of the three dimensional structure of the genome in the nucleus. 

PMID- 25374783
TI  - No sex-biased dispersal in a primate with an uncommon social system-cooperative
      polyandry.
AB  - An influential hypothesis proposed by Greenwood (1980) suggests that different
      mating systems result in female and male-biased dispersal, respectively, in birds
      and mammals. However, other aspects of social structure and behavior can also
      shape sex-biased dispersal. Although sex-specific patterns of kin cooperation are
      expected to affect the benefits of philopatry and dispersal patterns, empirical
      evidence is scarce. Unlike many mammals, Saguinus geoffroyi (Geoffroy's tamarin)
      has a breeding system in which typically multiple males mate with a single
      breeding female. Males typically form cooperative reproductive partnerships
      between relatives, whereas females generally compete for reproductive
      opportunities. This system of cooperative polyandry is predicted to result in
      female-biased dispersal, providing an opportunity to test the current hypotheses
      of sex-biased dispersal. Here we test for evidence of sex-biased dispersal in S.
      geoffroyi using demographic and genetic data from three populations. We find no
      sex bias in natal dispersal, contrary to the prediction based on the mating
      patterns. This pattern was consistent after controlling for the effects of
      historical population structure. Limited breeding opportunities within social
      groups likely drive both males and females to disperse, suggesting that dispersal
      is intimately related to the social context. The integration of genetic and field
      data revealed that tamarins are another exception to the presumed pattern of male
      biased dispersal in mammals. A shift in focus from mating systems to social
      behavior, which plays a role in most all processes expected to influence sex-bias
      in dispersal, will be a fruitful target for research both within species and
      across taxa. 

PMID- 25374784
TI  - Characterization of the transcriptome, nucleotide sequence polymorphism, and
      natural selection in the desert adapted mouse Peromyscus eremicus.
AB  - As a direct result of intense heat and aridity, deserts are thought to be among
      the most harsh of environments, particularly for their mammalian inhabitants.
      Given that osmoregulation can be challenging for these animals, with failure
      resulting in death, strong selection should be observed on genes related to the
      maintenance of water and solute balance. One such animal, Peromyscus eremicus, is
      native to the desert regions of the southwest United States and may live its
      entire life without oral fluid intake. As a first step toward understanding the
      genetics that underlie this phenotype, we present a characterization of the P.
      eremicus transcriptome. We assay four tissues (kidney, liver, brain, testes) from
      a single individual and supplement this with population level renal transcriptome
      sequencing from 15 additional animals. We identified a set of transcripts
      undergoing both purifying and balancing selection based on estimates of Tajima's
      D. In addition, we used the branch-site test to identify a transcript-Slc2a9,
      likely related to desert osmoregulation-undergoing enhanced selection in P.
      eremicus relative to a set of related non-desert rodents. 

PMID- 25374785
TI  - Study of the effect on shelter cat intakes and euthanasia from a shelter neuter
      return project of 10,080 cats from March 2010 to June 2014.
AB  - Cat impoundments were increasing at the municipal San Jose animal shelter in
      2009, despite long-term successful low cost sterilization programs and attempts
      to lower the euthanasia rate of treatable-rehabilitatable impounds beginning in
      2008. San Jose Animal Care and Services implemented a new strategy designed to
      control overall feral cat reproduction by altering and returning feral cats
      entering the shelter system, rather than euthanizing the cats. The purpose of
      this case study was to determine how the program affected the shelter cat intakes
      over time. In just over four years, 10,080 individual healthy adult feral cats,
      out of 11,423 impounded at the shelter during this time frame, were altered and
      returned to their site of capture. Included in the 11,423 cats were 862 cats
      impounded from one to four additional times for a total of 958 (9.5%) recaptures
      of the previously altered 10,080 cats. The remaining 385 healthy feral cats were
      euthanized at the shelter from March 2010 to June 2014. Four years into the
      program, researchers observed cat and kitten impounds decreased 29.1%; euthanasia
      decreased from over 70% of intakes in 2009, to 23% in 2014. Euthanasia in the
      shelter for Upper Respiratory Disease decreased 99%; dead cat pick up off the
      streets declined 20%. Dog impounds did not similarly decline over the four years.
      No other laws or program changes were implemented since the beginning of the
      program. 

PMID- 25374786
TI  - Use of Twitter to monitor attitudes toward depression and schizophrenia: an
      exploratory study.
AB  - Introduction. The paper reports on an exploratory study of the usefulness of
      Twitter for unobtrusive assessment of stigmatizing attitudes in the community.
      Materials and Methods. Tweets with the hashtags #depression or #schizophrenia
      posted on Twitter during a 7-day period were collected. Tweets were categorised
      based on their content and user information and also on the extent to which they
      indicated a stigmatising attitude towards depression or schizophrenia
      (stigmatising, personal experience of stigma, supportive, neutral, or anti
      stigma). Tweets that indicated stigmatising attitudes or personal experiences of
      stigma were further grouped into the following subthemes: social distance,
      dangerousness, snap out of it, personal weakness, inaccurate beliefs, mocking or
      trivializing, and self-stigma. Results and Discussion. Tweets on depression
      mostly related to resources for consumers (34%), or advertised services or
      products for individuals with depression (20%). The majority of schizophrenia
      tweets aimed to increase awareness of schizophrenia (29%) or reported on research
      findings (22%). Tweets on depression were largely supportive (65%) or neutral
      (27%). A number of tweets were specifically anti-stigma (7%). Less than 1% of
      tweets reflected stigmatising attitudes (0.7%) or personal experience of stigma
      (0.1%). More than one third of the tweets which reflected stigmatising attitudes
      were mocking or trivialising towards individuals with depression (37%). The
      attitude that individuals with depression should "snap out of it" was evident in
      30% of the stigmatising tweets. The majority of tweets relating to schizophrenia
      were categorised as supportive (42%) or neutral (43%). Almost 10% of tweets were
      explicitly anti-stigma. The percentage of tweets showing stigmatising attitudes
      was 5%, while less than 1% of tweets described personal experiences of
      stigmatising attitudes towards individuals with schizophrenia. Of the tweets that
      indicated stigmatising attitudes, most reflected inaccurate beliefs about
      schizophrenia being multiple personality disorder (52%) or mocked or trivialised
      individuals with schizophrenia (33%). Conclusions. The study supports the use of
      analysis of Twitter content to unobtrusively measure attitudes towards mental
      illness, both supportive and stigmatising. The results of the study may be useful
      in assisting mental health promotion and advocacy organisations to provide
      information about resources and support, raise awareness and counter common
      stigmatising attitudes. 

PMID- 25374787
TI  - Comparison of predictor approaches for longitudinal binary outcomes: application
      to anesthesiology data.
AB  - Longitudinal data with binary repeated responses are now widespread among
      clinical studies and standard statistical analysis methods have become inadequate
      in the answering of clinical hypotheses. Instead of such conventional approaches,
      statisticians have started proposing better techniques, such as the Generalized
      Estimating Equations (GEE) approach and Generalized Linear Mixed Models (GLMM)
      technique. In this research, we undertook a comparative study of modeling binary
      repeated responses using an anesthesiology dataset which has 375 patient data
      with clinical variables. We modeled the relationship between hypotension and age,
      gender, surgical department, positions of patients during surgery, diastolic
      blood pressure, pulse, electrocardiography and doses of Marcain-heavy,
      chirocaine, fentanyl, and midazolam. Moreover, parameter estimates between the
      GEE and the GLMM were compared. The parameter estimates, except time-after,
      Marcain-Heavy, and Fentanyl from the GLMM, are larger than those from GEE. The
      standard errors from the GLMM are larger than those from GEE. GLMM appears to be
      more suitable approach than the GEE approach for the analysis hypotension during
      spinal anesthesia. 

PMID- 25374788
TI  - Are improper kinetic models hampering drug development?
AB  - Reproducibility of biological data is a significant problem in research today.
      One potential contributor to this, which has received little attention, is the
      over complication of enzyme kinetic inhibition models. The over complication of
      inhibitory models stems from the common use of the inhibitory term (1 + [I]/Ki ),
      an equilibrium binding term that does not distinguish between inhibitor binding
      and inhibitory effect. Since its initial appearance in the literature, around a
      century ago, the perceived mechanistic methods used in its production have
      spurred countless inhibitory equations. These equations are overly complex and
      are seldom compared to each other, which has destroyed their usefulness resulting
      in the proliferation and regulatory acceptance of simpler models such as IC50s
      for drug characterization. However, empirical analysis of inhibitory data
      recognizing the clear distinctions between inhibitor binding and inhibitory
      effect can produce simple logical inhibition models. In contrast to the common
      divergent practice of generating new inhibitory models for every inhibitory
      situation that presents itself. The empirical approach to inhibition modeling
      presented here is broadly applicable allowing easy comparison and rational
      analysis of drug interactions. To demonstrate this, a simple kinetic model of
      DAPT, a compound that both activates and inhibits gamma-secretase is examined
      using excel. The empirical kinetic method described here provides an improved way
      of probing disease mechanisms, expanding the investigation of possible
      therapeutic interventions. 

PMID- 25374789
TI  - Horizontal transfer generates genetic variation in an asexual pathogen.
AB  - There are major gaps in the understanding of how genetic variation is generated
      in the asexual pathogen Verticillium dahliae. On the one hand, V. dahliae is a
      haploid organism that reproduces clonally. On the other hand, single-nucleotide
      polymorphisms and chromosomal rearrangements were found between V. dahliae
      strains. Lineage-specific (LS) regions comprising about 5% of the genome are
      highly variable between V. dahliae strains. Nonetheless, it is unknown whether
      horizontal gene transfer plays a major role in generating genetic variation in V.
      dahliae. Here, we analyzed a previously sequenced V. dahliae population of nine
      strains from various geographical locations and hosts. We found highly homologous
      elements in LS regions of each strain; LS regions of V. dahliae strain JR2 are
      much richer in highly homologous elements than the core genome. In addition, we
      discovered, in LS regions of JR2, several structural forms of nonhomologous
      recombination, and two or three homologous sequence types of each form, with
      almost each sequence type present in an LS region of another strain. A large
      section of one of the forms is known to be horizontally transferred between V.
      dahliae strains. We unexpectedly found that 350 kilobases of dynamic LS regions
      were much more conserved than the core genome between V. dahliae and a closely
      related species (V. albo-atrum), suggesting that these LS regions were
      horizontally transferred recently. Our results support the view that genetic
      variation in LS regions is generated by horizontal transfer between strains, and
      by chromosomal reshuffling reported previously. 

PMID- 25374790
TI  - A large-scale field study examining effects of exposure to clothianidin seed
      treated canola on honey bee colony health, development, and overwintering
      success.
AB  - In summer 2012, we initiated a large-scale field experiment in southern Ontario,
      Canada, to determine whether exposure to clothianidin seed-treated canola (oil
      seed rape) has any adverse impacts on honey bees. Colonies were placed in
      clothianidin seed-treated or control canola fields during bloom, and thereafter
      were moved to an apiary with no surrounding crops grown from seeds treated with
      neonicotinoids. Colony weight gain, honey production, pest incidence, bee
      mortality, number of adults, and amount of sealed brood were assessed in each
      colony throughout summer and autumn. Samples of honey, beeswax, pollen, and
      nectar were regularly collected, and samples were analyzed for clothianidin
      residues. Several of these endpoints were also measured in spring 2013. Overall,
      colonies were vigorous during and after the exposure period, and we found no
      effects of exposure to clothianidin seed-treated canola on any endpoint measures.
      Bees foraged heavily on the test fields during peak bloom and residue analysis
      indicated that honey bees were exposed to low levels (0.5-2 ppb) of clothianidin
      in pollen. Low levels of clothianidin were detected in a few pollen samples
      collected toward the end of the bloom from control hives, illustrating the
      difficulty of conducting a perfectly controlled field study with free-ranging
      honey bees in agricultural landscapes. Overwintering success did not differ
      significantly between treatment and control hives, and was similar to
      overwintering colony loss rates reported for the winter of 2012-2013 for
      beekeepers in Ontario and Canada. Our results suggest that exposure to canola
      grown from seed treated with clothianidin poses low risk to honey bees. 

PMID- 25374791
TI  - A global phylogenetic analysis in order to determine the host species and
      geography dependent features present in the evolution of avian H9N2 influenza
      hemagglutinin.
AB  - A complete phylogenetic analysis of all of the H9N2 hemagglutinin sequences that
      were collected between 1966 and 2012 was carried out in order to build a picture
      of the geographical and host specific evolution of the hemagglutinin protein. To
      improve the quality and applicability of the output data the sequences were
      divided into subsets based upon location and host species. The phylogenetic
      analysis of hemagglutinin reveals that the protein has distinct lineages between
      China and the Middle East, and that wild birds in both regions retain a distinct
      form of the H9 molecule, from the same lineage as the ancestral hemagglutinin.
      The results add further evidence to the hypothesis that the current predominant
      H9N2 hemagglutinin lineage might have originated in Southern China. The study
      also shows that there are sampling problems that affect the reliability of this
      and any similar analysis. This raises questions about the surveillance of H9N2
      and the need for wider sampling of the virus in the environment. The results of
      this analysis are also consistent with a model where hemagglutinin has
      predominantly evolved by neutral drift punctuated by occasional selection events.
      These selective events have produced the current pattern of distinct lineages in
      the Middle East, Korea and China. This interpretation is in agreement with
      existing studies that have shown that there is widespread intra-country sequence
      evolution. 

PMID- 25374792
TI  - Exosomes Function in Pro- and Anti-Angiogenesis.
AB  - Exosomes, a group of small vesicles (30-100 nm), originate when the inward
      budding of the endosomal membrane forms multivesicular bodies (MVBs). Exosomes
      are released into the extracellular space when the MVBs fuse with the plasma
      membrane. Numerous studies have indicated that exosomes play critical roles in
      mediating cell-to-cell communication. Also, exosomes are believed to possess a
      powerful capacity in regulating cell survival/death, inflammation and tumor
      metastasis, depending on the particular array of molecules contained within a
      particular population of exosomes. This mini-review will summarize dual roles of
      exosomes derived from different types of cells (i.e. endothelial cells, tumor
      cells, platelets, bone-marrow stem cells, cardiomyocytes, myocardial progenitor
      cells and among others) in endothelial cell proliferation, migration and tube
      like formation. In particular, this review will focus on the therapeutic
      potential of exosomes as a natural nano-particle for delivering pro-/anti
      angiogenic factors (proteins, mRNAs and microRNAs) into endothelial cells.

PMID- 25374793
TI  - Actinomycosis of the appendix in childhood- an unusual cause of appendicitis.
AB  - Actinomycosis is a rare chronic bacterial infectious disease in childhood. A 14
      year-old boy admitted with cramping abdominal pain and vomiting. Physical
      examination revealed right lower quadrant tenderness. Appendectomy was performed.
      On the histological section, typical actinomycotic (sulfur) granules in the
      appendiceal lumen were observed. 

PMID- 25374794
TI  - Staged Closure of Giant Omphalocele using Synthetic Mesh.
AB  - Giant omphalocele is difficult to manage and is associated with a poor outcome. A
      male newborn presented to our hospital with a giant omphalocele. We performed a
      staged closure of giant omphalocele using synthetic mesh to construct a silo and
      then mesh abdominoplasty in the neonatal period that led to a successful outcome
      within a reasonable period of hospital stay. 

PMID- 25374795
TI  - Fetus in fetu: report of two cases.
AB  - Fetus-in-fetu (FIF) is a rare and interesting entity characterized
      byincorporation of a malformed, monozygotic, diamnionic parasitic twin into the
      body of other normal twin partner. FIF is differentiated from teratoma by its
      embryological origin, its unusual location in the retroperitoneal space and the
      presence of vertebral column (axis) often with appropriate arrangement of other
      organs or limbs around this axis. We report two cases of FIF. Our first case
      presented at 18 months, while second at 9 year of age. FIF derived their blood
      supply directly from aorta in both the cases.Our FIF had distinct fetoid
      features, well developed axial skeleton with a complete spinal column, trunk,
      intestinal loops, four limbs, well developed fingers and toes, male external
      genitalia and abundant scalp hairs. Their weightwas 600 grams and 800 grams,
      respectively. Postoperative period was smooth and on long-term follow up no
      evidence of recurrence was seen in both the patients. 

PMID- 25374796
TI  - Appendicular Band Syndrome simulating Appendicular Mass in a Child.
AB  - Appendicular band syndrome is an exceedingly rare surgical emergency that may
      lead to intestinal obstruction and strangulation. We report a case of 2-year-old
      boy who presented with acute intestinal obstruction with a mass in right iliac
      fossa (RIF). At exploration, an inflamed appendix had entrapped a loop of
      terminal ileum leading to its strangulation and gangrene. The appendectomy and
      resection of gangrenous gut were done with formation of an ileostomy. 

PMID- 25374797
TI  - Mesh-repaired complete sternal cleft complicated by multi-resistant bacterial
      infection.
AB  - Sternal cleft is a very rare congenital anomaly, which can occur as an isolated
      or associated with other anomalies. We report a patient with a mesh-repaired
      complete sternal cleft complicated by infection with a multi-resistant
      Pseudomonas aeruginosa. The patch was surgically removed. 

PMID- 25374798
TI  - Primary spontaneous bilateral pneumothorax in a neonate.
AB  - Pneumothorax, though rare, is a recognized cause of respiratory distress in the
      immediate newborn period. It may occur spontaneously or secondary to various
      underlying lung diseases. Here we share our experience of a neonate with
      spontaneous pneumothorax with mild to moderate respiratory distress, who
      recovered completely with conservative management with an oxygen-enriched
      atmosphere and no surgical intervention. 

PMID- 25374799
TI  - Clear cell sarcoma of the kidney: report of two cases.
AB  - Clear cell sarcoma of kidney (CCSK) is an aggressive renal neoplasm. We report
      two boys aged three and half, and three years with CCSK, one of whom had a
      disease free survival of four years and eight months. These patients were managed
      with surgery, chemotherapy and radiotherapy. One of the patients discontinued
      treatment early and lost to follow up. Aggressive multimodality therapy is the
      keystone to improved outcome. 

PMID- 25374800
TI  - Giant retroperitoneal lipoma in an infant.
AB  - Lipomas can occur almost anywhere in the body, but retroperitoneal lipomas are
      extremely rare. They are slowly growing benign tumors and can attain an enormous
      size due to silent course of the disease. Total excision of the mass is the
      treatment of choice and is curative for benign retroperitoneal lipomas. We
      treated an 11-month-old female patient with giant retroperitoneal lipomas by
      surgical excision. Histopathology confirmed it as fibrolipoma. 

PMID- 25374801
TI  - Amyand's Hernia with Perforated Appendix in a Neonate.
AB  - When vermiform appendix is found in the inguinal hernial sac, the condition is
      called Amyand's hernia (AH). Appendix in hernial sac can be normal, inflamed or
      perforated. It can present as complicated hernia or acute scrotum. We present a
      case of Amyand's hernia in a 25-day-old male who presented with an obstructed
      hernia having perforated appendix in the hernial sac. 

PMID- 25374802
TI  - Pre-Sternal Abscess associated with Deep Neck Infection.

PMID- 25374803
TI  - Intensive care performance: How should we monitor performance in the future?
AB  - Intensive care faces economic challenges. Therefore, evidence proving both
      effectiveness and efficiency, i.e., cost-effectiveness, of delivered care is
      needed. Today, the quality of care is an important issue in the health care
      debate. How do we measure quality of care and how accurate and representative is
      this measurement? In the following report, several topics which are used for the
      evaluation of intensive care unit (ICU) performance are discussed: (1) The use of
      general outcome prediction models to determine the risk of patients who are
      admitted to ICUs in an increasing variety of case mix for the different intensive
      care units, together with three major limitations; (2) As critical care outcomes
      research becomes a more established entity, mortality is now only one of many
      endpoints that are relevant. Mortality is a limited outcome when assessing
      critical care performance, while patient interest in quality of life outcomes is
      relevant; and (3) The Quality Indicators Committee of the Society of Critical
      Care Medicine recommended that short-term readmission is a major performance
      indicator of the quality of intensive care medicine. 

PMID- 25374804
TI  - Focus on peripherally inserted central catheters in critically ill patients.
AB  - Venous access devices are of pivotal importance for an increasing number of
      critically ill patients in a variety of disease states and in a variety of
      clinical settings (emergency, intensive care, surgery) and for different purposes
      (fluids or drugs infusions, parenteral nutrition, antibiotic therapy, hemodynamic
      monitoring, procedures of dialysis/apheresis). However, healthcare professionals
      are commonly worried about the possible consequences that may result using a
      central venous access device (CVAD) (mainly, bloodstream infections and
      thrombosis), both peripherally inserted central catheters (PICCs) and centrally
      inserted central catheters (CICCs). This review aims to discuss indications,
      insertion techniques, and care of PICCs in critically ill patients. PICCs have
      many advantages over standard CICCs. First of all, their insertion is easy and
      safe -due to their placement into peripheral veins of the arm- and the advantage
      of a central location of catheter tip suitable for all osmolarity and pH
      solutions. Using the ultrasound-guidance for the PICC insertion, the risk of
      hemothorax and pneumothorax can be avoided, as well as the possibility of primary
      malposition is very low. PICC placement is also appropriate to avoid post
      procedural hemorrhage in patients with an abnormal coagulative state who need a
      CVAD. Some limits previously ascribed to PICCs (i.e., low flow rates, difficult
      central venous pressure monitoring, lack of safety for radio-diagnostic
      procedures, single-lumen) have delayed their start up in the intensive care units
      as common practice. Though, the recent development of power-injectable PICCs
      overcomes these technical limitations and PICCs have started to spread in
      critical care settings. Two important take-home messages may be drawn from this
      review. First, the incidence of complications varies depending on venous accesses
      and healthcare professionals should be aware of the different clinical
      performance as well as of the different risks associated with each type of CVAD
      (CICCs or PICCs). Second, an inappropriate CVAD choice and, particularly, an
      inadequate insertion technique are relevant-and often not recognized-potential
      risk factors for complications in critically ill patients. We strongly believe
      that all healthcare professionals involved in the choice, insertion or management
      of CVADs in critically ill patients should know all potential risk factors of
      complications. This knowledge may minimize complications and guarantee longevity
      to the CVAD optimizing the risk/benefit ratio of CVAD insertion and use. Proper
      management of CVADs in critical care saves lines and lives. Much evidence from
      the medical literature and from the clinical practice supports our belief that,
      compared to CICCs, the so-called power-injectable peripherally inserted central
      catheters are a good alternative choice in critical care. 

PMID- 25374805
TI  - Impact of perioperative hyponatremia in children: A narrative review.
AB  - For more than 50 years, hypotonic fluids (crystalloids) have been the standard
      for maintenance fluid used in children. In the last decade, several studies have
      evaluated the risk of hyponatremia associated with the use of hypotonic vs
      isotonic fluids, which has lead to an intense debate. Children undergoing surgery
      have several stimuli for release of antidiuretic hormone, which controls renal
      water handling, including pain, nausea, vomiting, narcotic use and blood loss.
      The body's primary defense against the development of hyponatremia is the ability
      of the kidneys to excrete free water and dilute urine. Increased levels of
      antidiuretic hormone can result in hyponatremia, defined as a plasma sodium level
      < 136 mmol/L, which causes cells to draw in excess water and swell. This
      manifests as central nervous system symptoms such as lethargy, irritability and
      seizures. The risk for symptomatic hyponatremia is higher in children than in
      adults. It represents an emergency condition, and early diagnosis, prompt
      treatment and close monitoring are essential to reduce morbidity and mortality.
      The widespread use of hypotonic fluids in children undergoing surgery is a matter
      of concern and more focus on this topic is urgently needed. In this paper, we
      review the literature and describe the impact of perioperative hyponatremia in
      children. 

PMID- 25374806
TI  - Invasive candidiasis in critical care setting, updated recommendations from
      "Invasive Fungal Infections-Clinical Forum", Iran.
AB  - Invasive candidiasis (IC) bears a high risk of morbidity and mortality in the
      intensive care units (ICU). With the current advances in critical care and the
      use of wide-spectrum antibiotics, invasive fungal infections (IFIs) and IC in
      particular, have turned into a growing concern in the ICU. Further to blood
      cultures, some auxiliary laboratory tests and biomarkers are developed to enable
      an earlier detection of infection, however these test are neither consistently
      available nor validated in our setting. On the other hand, patients' clinical
      status and local epidemiology data may justify the empiric antifungal approach
      using the proper antifungal option. The clinical approach to the management of IC
      in febrile, non-neutropenic critically ill patients has been defined in available
      international guidelines; nevertheless such recommendations need to be customized
      when applied to our local practice. Over the past three years, Iranian experts
      from intensive care and infectious diseases disciplines have tried to draw a
      consensus on the management of IFI with a particular focus on IC in the ICU. The
      established IFI-clinical forum (IFI-CF), comprising the scientific leaders in the
      field, has recently come up with and updated recommendation on the same (June
      2014). The purpose of this review is to put together literature insights and
      Iranian experts' opinion at the IFI-CF, to propose an updated practical overview
      on recommended approaches for the management of IC in the ICU. 

PMID- 25374808
TI  - Why do young people with chronic kidney disease die early?
AB  - Cardiovascular disease poses the greatest risk of premature death seen among
      patients with chronic kidney disease (CKD). Up to 50% of mortality risk in the
      dialysis population is attributable to cardiovascular disease and the largest
      relative excess mortality is observed in younger patients. In early CKD,
      occlusive thrombotic coronary disease is common, but those who survive to reach
      end-stage renal failure requiring dialysis are more prone to sudden death
      attributable mostly to sudden arrhythmic events and heart failure related to left
      ventricular hypertrophy, coronary vascular calcification and electrolyte
      disturbances. In this review, we discuss the basis of the interaction of
      traditional risk factors for cardiovascular disease with various pathological
      processes such as endothelial dysfunction, oxidative stress, low grade chronic
      inflammation, neurohormonal changes and vascular calcification and stiffness
      which account for the structural and functional cardiac changes that predispose
      to excess morbidity and mortality in young people with CKD. 

PMID- 25374807
TI  - Nephropathy in dietary hyperoxaluria: A potentially preventable acute or chronic
      kidney disease.
AB  - Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis, but also
      renal parenchymal disease histologically characterized by deposition of calcium
      oxalate crystals throughout the renal parenchyma, profound tubular damage and
      interstitial inflammation and fibrosis. Hyperoxaluric nephropathy presents
      clinically as acute or chronic renal failure that may progress to end-stage renal
      disease (ESRD). This sequence of events, well recognized in the past in primary
      and enteric hyperoxalurias, has also been documented in a few cases of dietary
      hyperoxaluria. Estimates of oxalate intake in patients with chronic dietary
      hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the
      reported average oxalate content of the diets of certain populations worldwide,
      thus raising the question whether dietary hyperoxaluria is a primary cause of
      ESRD in these regions. Studies addressing this question have the potential of
      improving population health and should be undertaken, alongside ongoing studies
      which are yielding fresh insights into the mechanisms of intestinal absorption
      and renal excretion of oxalate, and into the mechanisms of development of oxalate
      induced renal parenchymal disease. Novel preventive and therapeutic strategies
      for treating all types of hyperoxaluria are expected to develop from these
      studies. 

PMID- 25374809
TI  - Cardiovascular co-morbidity in chronic kidney disease: Current knowledge and
      future research needs.
AB  - Chronic kidney disease (CKD) is recognised as a health concern globally and leads
      to high rates of morbidity, mortality and healthcare expenditure. CKD is itself
      an independent risk factor for unfavorable health outcomes that include
      cardiovascular disease (CVD). Coronary artery disease is the primary type of CVD
      in CKD patients and a significant cause of death among renal transplant patients.
      Traditional and non-traditional risk factors for CVD exist in patients with CKD.
      Traditional factors include smoking, hypertension, dyslipidemia and diabetes
      which are highly prevalent in CKD patients. Non-traditional risk factors of CKD
      are mainly uraemia-specific and increase in prevalence as kidney function
      declines. Some examples of uraemia-specific risk factors that have been well
      documented include low levels of haemoglobin, albuminuria, and abnormal bone and
      mineral metabolism. Therapeutic interventions targeted at more traditional risk
      factors which contribute to CVD, have not had the desired effect on lowering CVD
      events and mortality in those suffering with CKD. Future research is warranted to
      delineate clear evidence to the benefit of modifying non-traditional risk
      factors. 

PMID- 25374810
TI  - Preeclampsia from a renal point of view: Insides into disease models, biomarkers
      and therapy.
AB  - Proteinuria is a frequently detected symptom, found in 20% of pregnancies. A
      common reason for proteinuria in pregnancy is preeclampsia. To diagnose
      preeclampsia clinically and to get new insights into the pathophysiology of the
      disease it is at first essential to be familiar with conditions in normal
      pregnancy. Animal models and biomarkers can help to learn more about disease
      conditions and to find new treatment strategies. In this article we review the
      changes in kidney function during normal pregnancy and the differential diagnosis
      of proteinuria in pregnancy. We summarize different pathophysiological theories
      of preeclampsia with a special focus on the renal facets of the disease. We
      describe the current animal models and give a broad overview of different
      biomarkers that were reported to predict preeclampsia or have a prognostic value
      in preeclampsia cases. We end with a summary of treatment options for
      preeclampsia related symptoms including the use of plasmapheresis as a rescue
      therapy for so far refractory preeclampsia. Most of these novel biomarkers for
      preeclampsia are not yet implemented in clinical use. Therefore, we recommend
      using proteinuria (measured by UPC ratio) as a screening parameter for
      preeclampsia. Delivery is the only curative treatment for preeclampsia. In early
      preeclampsia the primary therapy goal is to prolong pregnancy until a state were
      the child has an acceptable chance of survival after delivery. 

PMID- 25374812
TI  - Retrograde intrarenal surgery in pediatric patients.
AB  - Urinary tract stone disease is seen at a level of 1%-2% in childhood (< 18
      years). In recent years, however, there has been a marked increased in pediatric
      stone disease, particularly in adolescence. A carbohydrate- and salt-heavy diet
      and a more sedentary lifestyle are implicated in this increase. Although stone
      disease is rare in childhood, its presence is frequently associated with
      metabolic or anatomical disorders or infectious conditions, for which reason
      there is a high possibility of post-therapeutic recurrence. Factors such as a
      high possibility of recurrence and increasing incidence further enhance the
      importance of minimally invasive therapeutic options in children, with their
      expectations of a long life. In children in whom active stone removal is decided
      on, the way to achieve the highest level of success with the least morbidity is
      to select the most appropriate treatment modality. Thanks to today's advanced
      technology, renal stones that were once treated only by surgery can now be
      treated with minimally invasive techniques, from invasion of the urinary system
      in an antegrade (percutaneous nephrolithotomy) or retrograde (retrograde
      intrarenal surgery) manner or shock wave lithotripsy to laparoscopic stone
      surgery. This compilation study examined studies involving the RIRS procedure,
      the latest minimally invasive technique, in children and compared the results of
      those studies with those from other techniques. 

PMID- 25374811
TI  - Acute kidney injury due to bilateral ureteral obstruction in children.
AB  - Bilateral ureteral obstruction in children is a rare condition arising from
      several medical or surgical pictures. It needs to be promptly suspected in order
      to attempt a quick renal function recovery. In this paper we concentrated on
      uncommon causes of obstruction, with the aim of giving a summary of such
      multiple, rare and heterogeneous conditions joint together by the common
      denominator of sudden bilateral ureteral obstruction, difficult to be suspected
      at times. Conversely, typical and well-known diseases have been just run over. We
      considered pediatric cases of ureteral obstruction presenting as bilateral, along
      with some cases which truly appeared as single-sided, because of their potential
      bilateral presentation. We performed a review of the literature by a search on
      PubMed, CrossRef Metadata Search, internet and reference lists of single articles
      updated to May 2014, with no time limits in the past. Given that we deal with
      rare conditions, we decided to include also papers in non-English languages,
      published with an English abstract. For the sake of clearness, we divided our
      research results into 8 categories: (1) urolithiasis; (2) congenital urinary
      tract malformations; (3) immuno-rheumatologic causes of ureteral obstruction; (4)
      ureteral localization of infections; (5) other systemic infective causes of
      ureteral obstructions; (6) neoplastic intrinsic ureteral obstructions; (7)
      extrinsic ureteral obstructions; and (8) iatrogenic trigonal obstruction or
      inflammation. Of course, different pathogenic mechanisms underlay those clinical
      pictures, partly well-known and partly not completely understood. 

PMID- 25374813
TI  - Prostatic surgery associated acute kidney injury.
AB  - Acute kidney injury (AKI) is associated with extended hospital stays, high risks
      of in-hospital and long-term mortality, and increased risk of incident and
      progressive chronic kidney disease. Patients with urological diseases are a high
      risk group for AKI owing to the coexistence of obstructive uropathy, older age,
      and preexistent chronic kidney disease. Nonetheless, precise data on the
      incidence and outcomes of postoperative AKI in urological procedures are lacking.
      Benign prostatic hyperplasia and prostate cancer are common diagnoses in older
      men and are frequently treated with surgical procedures. Whereas severe AKI after
      prostate surgery in general appears to be unusual, AKI associated with
      transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis
      (RM) after radical prostatectomy have been frequently described. The purpose of
      this review is to discuss the current knowledge regarding the epidemiology, risk
      factors, outcomes, prevention, and treatment of AKI associated with prostatic
      surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries
      will be emphasized. 

PMID- 25374814
TI  - Metabolic syndrome and chronic kidney disease: Current status and future
      directions.
AB  - Metabolic syndrome (MetS) is a term used to denote a combination of selected,
      widely prevalent cardiovascular disease (CVD)-related risk factors. Despite the
      ambiguous definition of MetS, it has been clearly associated with chronic kidney
      disease markers including reduced glomerular filtration rate, proteinuria and/or
      microalbuminuria, and histopathological markers such as tubular atrophy and
      interstitial fibrosis. However, the etiological role of MetS in chronic kidney
      disease (CKD) is less clear. The relationship between MetS and CKD is complex and
      bidirectional, and so is best understood when CKD is viewed as a common
      progressive illness along the course of which MetS, another common disease, may
      intervene and contribute. Possible mechanisms of renal injury include insulin
      resistance and oxidative stress, increased proinflammatory cytokine production,
      increased connective tissue growth and profibrotic factor production, increased
      microvascular injury, and renal ischemia. MetS also portends a higher CVD risk at
      all stages of CKD from early renal insufficiency to end-stage renal disease.
      Clinical interventions for MetS in the presence of CKD should include a
      combination of weight reduction, appropriate dietary modification and increase
      physical activity, plus targeting of individual CVD-related risk factors such as
      dysglycemia, hypertension, and dyslipidemia while conforming to relevant national
      societal guidelines. 

PMID- 25374815
TI  - Chronic kidney disease and erectile dysfunction.
AB  - Erectile dysfunction (ED) is a common condition among male chronic kidney disease
      (CKD) patients. Its prevalence is estimated to be approximately 80% among these
      patients. It has been well established that the production of nitric oxide from
      the cavernous nerve and vascular endothelium and the subsequent production of
      cyclic GMP are critically important in initiating and maintaining erection.
      Factors affecting these pathways can induce ED. The etiology of ED in CKD
      patients is multifactorial. Factors including abnormalities in gonadal-pituitary
      system, disturbance in autonomic nervous system, endothelial dysfunction, anemia
      (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc
      deficiency, and psychological problems are implicated in the occurrence of ED. An
      improvement of general conditions is the first step of treatment. Sufficient
      dialysis and adequate nutritional intake are necessary. In addition, control of
      anemia and secondary hyperparathyroidism is required. Changes of drugs that
      potentially affect erectile function may be necessary. Further, zinc
      supplementation may be necessary when zinc deficiency is suspected.
      Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in
      CKD patients, and their efficacy was confirmed by many studies. Testosterone
      replacement therapy in addition to PDE5Is may be useful, particularly for CKD
      patients with hypogonadism. Renal transplantation may restore erectile function.
      ED is an early marker of cardiovascular disease (CVD), which it frequently
      precedes; therefore, it is crucial to examine the presence of ED in CKD patients
      not only for the improvement of the quality of life but also for the prevention
      of CVD attack. 

PMID- 25374816
TI  - Searching for a treatment for Alport syndrome using mouse models.
AB  - Alport syndrome (AS) is a hereditary nephritis caused by mutations in COL4A3,
      COL4A4 or COL4A5 encoding the type IV collagen alpha3, alpha4, and alpha5 chains,
      which are major components of the glomerular basement membrane. About 20 years
      have passed since COL4A3, COL4A4, and COL4A5 were identified and the first Alport
      mouse model was developed using a knockout approach. The phenotype of Alport mice
      is similar to that of Alport patients, including characteristic thickening and
      splitting of the glomerular basement membrane. Alport mice have been widely used
      to study the pathogenesis of AS and to develop effective therapies. In this
      review, the newer therapies for AS, such as pharmacological interventions,
      genetic approaches and stem cell therapies, are discussed. Although some stem
      cell therapies have been demonstrated to slow the renal disease progression in
      Alport mice, these therapies demand continual refinement as research advances. In
      terms of the pharmacological drugs, angiotensin-converting enzyme inhibitors have
      been shown to be effective in Alport mice. Novel therapies that can provide a
      better outcome or lead to a cure are still awaited. 

PMID- 25374817
TI  - Role of insulin resistance in uric acid nephrolithiasis.
AB  - Metabolic syndrome has been implicated in the pathogenesis of uric acid stones.
      Although not completely understood, its role is supported by many studies
      demonstrating increased prevalence of uric acid stones in patients with metabolic
      syndrome and in particular insulin resistance, a major component of metabolic
      syndrome. This review presents epidemiologic studies demonstrating the
      association between metabolic syndrome and nephrolithiasis in general as well as
      the relationship between insulin resistance and uric acid stone formation, in
      particular. We also review studies that explore the pathophysiologic relationship
      between insulin resistance and uric acid nephrolithiasis. 

PMID- 25374818
TI  - Ureteroscopy and stones: Current status and future expectations.
AB  - Urolithaisis is becoming an ever increasing urological, nephrological and primary
      care problem. With a lifetime prevalence approaching 10% and increasing morbidity
      due to stone disease, the role of ureteroscopy and stone removal is becoming more
      important. We discuss the current status of stone disease and review the ever
      increasing role that ureteroscopy has to play in its management. We discuss
      technological advances that have been made in stone management and give you an
      overview of when, how and why ureteroscopy is the most common treatment option
      for stone management. We touch on the role of robotic ureteroscopy and the future
      of ureteroscopy in the next 10 years. 

PMID- 25374819
TI  - Clinical audit, a valuable tool to improve quality of care: General methodology
      and applications in nephrology.
AB  - Evaluation and improvement of quality of care provided to the patients are of
      crucial importance in the daily clinical practice and in the health policy
      planning and financing. Different tools have been developed, including incident
      analysis, health technology assessment and clinical audit. The clinical audit
      consist of measuring a clinical outcome or a process, against well-defined
      standards set on the principles of evidence-based medicine in order to identify
      the changes needed to improve the quality of care. In particular, patients
      suffering from chronic renal diseases, present many problems that have been set
      as topics for clinical audit projects, such as hypertension, anaemia and mineral
      metabolism management. Although the results of these studies have been
      encouraging, demonstrating the effectiveness of audit, overall the present
      evidence is not clearly in favour of clinical audit. These findings call
      attention to the need to further studies to validate this methodology in
      different operating scenarios. This review examines the principle of clinical
      audit, focusing on experiences performed in nephrology settings. 

PMID- 25374820
TI  - From crystalluria to kidney stones, some physicochemical aspects of calcium
      nephrolithiasis.
AB  - Nephrolithiasis seems to be the result of crystal formation, aggregation and
      retention in the kidney during crystalluria. These processes have to occur within
      the short urinary transit time through the kidney being in the order of few
      minutes. Recently much work was done on rather qualitative aspects of
      nephrolithiasis like genetics, metabolism and morphology. In this review we try
      to provide some quantitative information on urinary supersaturation with respect
      to stone minerals, especially Ca oxalate (CaOx), on the formation and aggregation
      of CaOx crystals and on crystal retention in the kidney. The paper is centered on
      idiopathic Ca nephrolithiasis being the most frequent stone disease with only
      partially known pathogenesis. New aspects of the role of urinary macromolecules
      in stone formation and of the mechanism of crystal aggregation are provided. 

PMID- 25374822
TI  - Nutcracker syndrome.
AB  - The nutcracker phenomenon [left renal vein (LRV) entrapment syndrome] refers to
      compression of the LRV most commonly between abdominal aorta and superior
      mesenteric artery. Term of nutcracker syndrome (NCS) is used for patients with
      clinical symptoms associated with nutcracker anatomy. LRV entrapment divided into
      2 types: anterior and posterior. Posterior and right-sided NCSs are rare
      conditions. The symptoms vary from asymptomatic hematuria to severe pelvic
      congestion. Symptoms include hematuria, orthostatic proteinuria, flank pain,
      abdominal pain, varicocele, dyspareunia, dysmenorrhea, fatigue and orthostatic
      intolerance. Existence of the clinical features constitutes a basis for the
      diagnosis. Several imaging methods such as Doppler ultrasonography, computed
      tomography angiography, magnetic resonance angiography and retrograde venography
      are used to diagnose NCS. The management of NCS depends upon the clinical
      presentation and the severity of the LRV hypertension. The treatment options are
      ranged from surveillance to nephrectomy. Treatment decision should be based on
      the severity of symptoms and their expected reversibility with regard to
      patient's age and the stage of the syndrome. 

PMID- 25374821
TI  - T-cell ageing in end-stage renal disease patients: Assessment and clinical
      relevance.
AB  - End-stage renal disease (ESRD) patients have a defective T-cell-mediated immune
      system which is related to excessive premature ageing of the T-cell compartment.
      This is likely to be caused by the uremia-associated pro-inflammatory milieu,
      created by loss of renal function. Therefore, ESRD patients are highly
      susceptible for infections, have an increased risk for virus-associated cancers,
      respond poorly to vaccination and have an increased risk for atherosclerotic
      diseases. Three ageing parameters can be used to assess an immunological T-cell
      age. First, thymic output can be determined by assessing the T-cell receptor
      excision circles-content together with CD31 expression within the naive T cells.
      Second, the telomere length of T cells and third the T-cell differentiation
      status are also indicators of T-cell ageing. Analyses based on these parameters
      in ESRD patients revealed that the immunological T-cell age is increased by on
      average 20 years compared to the chronological age. After kidney transplantation
      (KTx) the aged T-cell phenotype persists although the pro-inflammatory milieu is
      diminished. This might be explained by epigenetic modifications at hematopoietic
      stem cells level. Assessment of an immunological T-cell age could be an important
      tool to identify KTx recipients who are at risk for allograft rejection or to
      prevent over-immunosuppression. 

PMID- 25374823
TI  - Usefulness of hounsfield unit and density in the assessment and treatment of
      urinary stones.
AB  - Computed tomography (CT) is widely used to examine stones in the urinary system.
      In addition to the size and location of the stone and the overall health of the
      kidney, CT can also assess the density of the stone in Hounsfield units (HU). The
      HU, or Hounsfield density, measured by CT, is related to the density of the
      tissue or stone. A number of studies have assessed the use of HU in urology. HUs
      have been used to predict the type and opacity of stones during diagnosis, and
      the efficacy has been assessed using methods including extracorporeal shock wave
      lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureterorenoscopic
      ureterolithotripsy (URSL), and medical expulsive treatment (MET). Previous
      studies have focused on the success rate of HU for predicting the type of stone
      and of ESWL treatment. Understanding the composition of the stone plays a key
      role in determining the most appropriate treatment modality. The most recent
      reports have suggested that the HU value and its variants facilitate prediction
      of stone composition. However, the inclusion of data regarding urine, such as pH
      and presence of crystals, increases the predictive accuracy. HUs, which now form
      part of the clinical guidelines, allow us to predict the success of ESWL;
      therefore, they should be taken into account when ESWL is considered as a
      treatment option. However, there are currently insufficient data available
      regarding the value of HU for assessing the efficacy of PCNL, URSL, and MET.
      Studies performed to date suggest that these values would make a significant
      contribution to the diagnosis and treatment of urinary system stones. However,
      more data are required to assess this further. 

PMID- 25374824
TI  - Renal biopsy practice: What is the gold standard?
AB  - Renal biopsy (RB) is useful for diagnosis and therapy guidance of renal diseases
      but incurs a risk of bleeding complications of variable severity, from transitory
      haematuria or asymptomatic hematoma to life-threatening hemorrhage. Several risk
      factors for complications after RB have been identified, including high blood
      pressure, age, decreased renal function, obesity, anemia, low platelet count and
      hemostasis disorders. These should be carefully assessed and, whenever possible,
      corrected before the procedure. The incidence of serious complications has become
      low with the use of automated biopsy devices and ultrasound guidance, which is
      currently the "gold standard" procedure for percutaneous RB. An outpatient biopsy
      may be considered in a carefully selected population with no risk factor for
      bleeding. However, controversies persist on the duration of observation after
      biopsy, especially for native kidney biopsy. Transjugular RB and laparoscopic RB
      represent reliable alternatives to conventional percutaneous biopsy in patients
      at high risk of bleeding, although some factors limit their use. This aim of this
      review is to summarize the issues of complications after RB, assessment of
      hemorrhagic risk factors, optimal biopsy procedure and strategies aimed to
      minimize the risk of bleeding. 

PMID- 25374825
TI  - Regulatory roles of nitric oxide and angiotensin II on renal tubular transport.
AB  - Renal tubules regulate blood pressure and humoral homeostasis. Mediators that
      play a significant role in regulating the transport of solutes and water include
      angiotensin II (AngII) and nitric oxide (NO). AngIIcan significantly raise blood
      pressure via effects on the heart, vasculature, and renal tubules. AngII
      generally stimulates sodium reabsorption by triggering sodium and fluid retention
      in almost all segments of renal tubules. Stimulation of renal proximal tubule
      (PT) transport is thought to be essential for AngII-mediated hypertension.
      However, AngII has a biphasic effect on in vitro PT transport in mice, rats, and
      rabbits: stimulation at low concentrations and inhibition at high concentrations.
      On the other hand, NO is generally thought to inhibit renal tubular transport. In
      PTs, NO seems to be involved in the inhibitory effect of AngII. A recent study
      reports a surprising finding: AngII has a monophasic stimulatory effect on human
      PT transport. Detailed analysis of signalling mechanisms indicates that in
      contrast to other species, the human NO/guanosine 3',5'-cyclic
      monophosphate/extracellular signal-regulated kinase pathway seems to mediate this
      effect of Ang II on PT transport. In this review we will discuss recent progress
      in understanding the effects of AngII and NO on renal tubular transport. 

PMID- 25374826
TI  - Roles of the (pro)renin receptor in the kidney.
AB  - Prorenin receptor (PRR) is a multi-functioning protein possessing at least four
      different roles: (1) working as a receptor for renin and prorenin producing
      angiotensin I from angiotensinogen thus enhancing the tissue renin-angiotensin
      system; (2) inducing intracellular signals when a ligand binds to PRR; (3)
      participating in the functions of vacuolar proton ATPase; and (4) constituting
      the Wnt signaling receptor complex. Here, the roles of PRR in kidney physiology
      and diabetic conditions as well as recent findings regarding a soluble form of
      PRR are discussed. We also propose the possible mechanism concerning diabetic
      nephropathy as "trade-off hypothesis" from a PRR point of view. In brief, under
      hyperglycemic conditions, injured podocytes degrade degenerated proteins and
      intracellular organelles which require V-ATPase and PRR for vesicle internal
      acidification. Sustained hyperglycemia overproduces PRR molecules, which are
      transported to the transmembrane and bind to increased serum prorenin in the
      diabetic condition. This enhances tissue renin-angiotensin system and PRR
      mediated mitogen-activated protein kinase signals, resulting in increased
      injurious molecules such as transforming growth factor-beta, cyclooxygenase2,
      interleukin-1beta, and tumor necrosis factor-alpha ending in diabetic nephropathy
      progression. Although many findings led us to better PRR understanding, future
      works should elucidate which PRR functions, of the four discussed here, are
      dominant in each cell and kidney disease context. 

PMID- 25374827
TI  - Quality of life in end stage renal disease patients.
AB  - AIM: To understand factors associated with quality of life (QOL), examine types
      of QOL instruments, and determine need for further improvements in QOL
      assessment. METHODS: The method used databases (Pubmed, Google scholar) and a
      bibliographic search using key words QOL, end stage renal disease, Hemodialysis,
      Peritoneal dialysis, instruments to measure QOL, patients and
      qualitative/quantitative analysis published during 1990 to June 2014. Each
      article was assessed for sample size, demographics of participants, study design
      and type of QOL instruments used. We used WHO definition of QOL. RESULTS: For
      this review, 109 articles were screened, out of which 65 articles were selected.
      Out of 65 articles, there were 19 reports/reviews and 12 questionnaire manuals.
      Of the 34 studies, 82% were quantitative while only 18% were qualitative. QOL
      instruments measured several phenomenon such as physical/psychological health,
      effects and burdens of kidney disease, social support etc. those are associated
      with QOL. Few studies looked at spiritual beliefs, cultural beliefs, personal
      concerns, as per the WHO definition. Telemedicine and Palliative care have now
      been successfully used however QOL instruments seldom addressed those in the
      articles reviewed. Also noticed was that longitudinal studies were rarely
      conducted. Existing QOL instruments only partially measure QOL. This may limit
      validity of predictive power of QOL. CONCLUSION: Culture and disease specific QOL
      instruments that assess patients' objective and subjective experiences covering
      most aspects of QOL are urgently needed.

PMID- 25374829
TI  - Evaluation of initial stability and crestal bone loss in immediate implant
      placement: An in vivo study.
AB  - OBJECTIVES: (1) To measure the crestal bone levels around implants immediately,
      and one month, three months, and six months after immediate implant placement, to
      evaluate the amount of bone level changes in six months. (2) To measure the
      initial stability in immediate implant placement. MATERIALS AND METHODS: Ten
      patients were selected and a total of ten implants were placed in the immediate
      extraction sites. The change in the level of crestal bone was measured on
      standardized digital periapical radiographs taken at baseline, first month, third
      month, and sixth months for each patient, using the SOPRO imaging software. The
      initial stability of implants was measured with resonance frequency analysis
      (RFA) and an engine-driven torque. The measurements were statistically analyzed.
      The student's t-test was used, to identify the significance of the study
      parameters. RESULTS: When mesial and distal bone losses were averaged, the
      radiographic evaluation with the SOPRO imaging software showed an average of 0.80
      mm, with a standard deviation of +/- 0.18 mm bone loss at the first month,
      followed by 1.03 mm with a standard deviation of +/- 0.19 mm at the third month,
      and 1.23 mm with standard deviation of +/- 0.6 mm at the sixth month. The initial
      stability with the RFA instrument showed a mean of 55 implant stability quotient
      (ISQ) values and the torque showed a value of 36.50 Nm. CONCLUSIONS: The implant
      has to be placed 2 mm below the crestal bone level to compensate the crestal bone
      loss. The initial stability is achieved by apical preparation of the socket wall
      and use of straight screw implants. When the defect is more than 2 mm, autogenous
      grafts with membranes are the best choice.

PMID- 25374828
TI  - Residual urinary output in high body mass index individuals on chronic
      hemodialysis: A disregarded life vest?
AB  - AIM: To assess residual diuresis and diverse variables according to body mass
      index (BMI). METHODS: Cross-sectional study (n = 57), with 3 groups. Group A: BMI
      < 25, n = 22; Group B: BMI 25-30, n = 15; Group C: BMI > 30, n = 20. Diuresis,
      hematocrit, albumin, C-reactive protein, Malnutrition inflammatory score, Pro
      BNP, Troponin T, leptin and insulin levels are expressed as median and ranges
      (r). RESULTS: Albumin (g/dL): GA vs GC, 3.70 (r2.20-4.90) vs 3.85 (r3.40-4.90), P
      = 0.02. Diuresis (mL/d): GA 690 (r0-1780); GB 660 (r60-1800); GC 840 (r40-2840).
      Diuresis GA vs GC, P = 0.01. Leptin (ng/mL): GA vs GC, 3.81 (r0.78-69.60) vs GC,
      32.80 (r0.78-124.50), P < 0.001. Insulin (uU/mL): GA vs GB, 7 (r2-44) vs 11.50
      (r4-38), P = 0.02; GA vs GC, 7 (r2-44) vs 19.5 (r5-155), P = 0.0001. Troponin T
      and Pro-BNP levels were not different. Significant correlations: GC, Insulin-UF:
      rho = 0.53; P = 0.03; TroponinT-diuresis: rho = -0.48, P < 0.05; Pro-BNP
      diuresis: rho = -0.39, P < 0.01; Troponin T-ProBNP: rho = 0.77, P < 0.0001;
      albumin-Troponin T: rho = -0.66, P < 0.0001; albumin-ProBNP: rho = -0.44, P <
      0.05. CONCLUSION: High BMI associated positively with higher diuresis and
      albuminemia, and negatively with TropT and Pro-BNP. High BMI-associated better
      survival may be explained by better urinary output, lowering cardiovascular
      stress.

PMID- 25374830
TI  - A survey assessing modes of maintaining denture hygiene among elderly patients.
AB  - OBJECTIVE: To determine the denture hygiene habits in complete denture wearers.
      MATERIALS AND METHODS: In this study, a self-administered structured
      questionnaire was developed to know the attitude of the patients from the
      Department of Prosthodontics regarding denture hygiene. The study sample
      consisted of totally 500 subjects, which included 284 (56.8%) males and 216
      (43.2%) females. Data were analyzed using SPSS version 15.0 with Chi-square
      (chi(2)) test at P < 0.05. RESULTS: Nearly half of the subjects cleaned their
      dentures daily once. Participants from the younger age group and who had been
      wearing dentures since 2 years maintained better frequency of cleaning. The
      majority of these subjects used water and brush for denture cleansing. After
      seeing the condition, more than half of the dentures were rated as poor (60%).
      There was significant difference between all the groups on comparison (P =
      0.001). CONCLUSION: Poor condition of complete dentures seen in the population is
      mainly due to irregular cleansing habits and also less usage of cleansing
      solutions. Dentists should give proper instructions regarding maintenance of
      denture hygiene.

PMID- 25374831
TI  - Effect of tetracycline HCl in the treatment of chronic periodontitis - A clinical
      study.
AB  - OBJECTIVE: This study was aimed to evaluate the efficacy of the adjunctive use of
      tetracycline fibers (Periodontal Plus AB((r))) as a local drug delivery with
      scaling and root planing, as compared with the results of one episode of scaling
      and root planing for the treatment of chronic periodontitis. MATERIALS AND
      METHODS: The effectiveness of Periodontal Plus AB (tetracycline fiber) was
      assessed in 100 patients suffering from chronic periodontitis using split-mouth
      technique. STATISTICAL ANALYSIS: The relative efficacy of the two treatment
      modalities was evaluated using the paired Student's t-test, and the comparative
      evaluation between the two groups was done using the independent Student's t
      test. RESULTS: Significant improvement was found in all the variables, including
      reduction in pocket depth and gain in clinical attachment level, in both test and
      control groups in 3 months, which was statistically significant. Mean reduction
      in pocket depth and gain in clinical attachment level were more in test than in
      control group. CONCLUSION: Tetracycline fiber therapy along with scaling and root
      planing improves the healing outcome, namely, reduction in pocket depth and gain
      in clinical attachment level, when compared to scaling and root planing alone.

PMID- 25374832
TI  - Oral health related knowledge, attitude, and practice among the pre-university
      students of Mysore city.
AB  - OBJECTIVES: To determine the oral health related behavior, knowledge, attitudes,
      and practices of pre-university students of Mysore city. DESIGN: A cross
      sectional descriptive study was conducted among 1000 pre-university students of
      Mysore city. RESULTS: Statistical tests such as percentage distribution and Chi
      square were used. P values <0.05 were considered statistically significant. Most
      of the students (88%, n = 880) knew that dental health reflects on the general
      health. Eighty-nine percent (n = 890) of students were aware that sweets and
      sticky food cause dental decay. Majority of the students (90%, n = 900) agreed
      that they visited dentist only when they had pain and cleaned their teeth once
      daily using toothbrush and tooth paste in vertical and horizontal motion.
      CONCLUSION: The study showed that the students had good knowledge about the basic
      oral health measures necessary to maintain proper oral health, but their attitude
      and practices toward oral health was relatively poor.

PMID- 25374833
TI  - Knowledge, attitude, and practice of hand hygiene among dentists practicing in
      Bangalore city - A cross-sectional survey.
AB  - BACKGROUND: Hand hygiene in dental practice is one of the most important parts of
      the infection control process to reduce the risk of transmitting microorganisms
      from provider to patient. The Centers for Disease Control and Prevention (CDC)
      Hand Hygiene (HH) guidelines were published more than 5 years ago. The extent to
      which dental practitioners are aware of it and the extent to which alcohol-based
      hand sanitizers are used by dental practitioners are unknown. AIMS AND
      OBJECTIVES: The aim of the present study was to assess the practice of HH among
      dentists in Bangalore city. The objectives of the study were to assess knowledge
      and attitudes among dentists with regard to HH in Bangalore city. MATERIALS AND
      METHODS: A total of 204 dentists from the registry of dental care facility,
      Bangalore, were selected for this study. The data were collected by administering
      a specially designed proforma. RESULTS: 51% of the dental practitioners use soap
      and water for HH frequently and 44.6% use alcohol-based hand sanitizers for HH
      frequently. Also, 53.4% were aware of the CDC HH guideline. One-third of the
      dental practitioners indicated that they have limited/moderate knowledge of the
      CDC HH guideline. CONCLUSION: Most dental practitioners use soap and water for HH
      frequently, and a smaller number of dental practitioners use alcohol-based hand
      sanitizers for HH frequently. The knowledge of the CDC HH guidelines needs to be
      improved.

PMID- 25374834
TI  - Effect of end-stage renal disease on oral health in patients undergoing renal
      dialysis: A cross-sectional study.
AB  - AIMS AND OBJECTIVES: To evaluate the effect of chronic renal failure on oral
      health in renal dialysis patients. To assess and improvise awareness of staff
      regarding oral health care of the patients in hemodialysis unit. MATERIALS AND
      METHODS: A cross-sectional questionnaire survey and oral health examination study
      were conducted on 206 end-stage chronic renal failure patients (stage V) who were
      undergoing renal dialysis in Guntur city. The study included the questionnaire
      form and modified WHO proforma to record their oral health status. Oral
      examination was done in American Dental Association (ADA) type III method by
      using mouth mirror and community periodontal index (CPI) probe. Questionnaire
      survey was conducted among the nursing staff in the hemodialysis unit. RESULTS:
      Mean age of the study subjects was 46.79 +/- 12.78 years; 81.1% were males and
      18.9% were females. Candidiasis (8.3%) was the most frequently seen oral mucosal
      condition in these subjects. Majority of the subjects (44.2%) showed periodontal
      diseases (CPI score 3: Pocket depth of 4-5 mm). Caries prevalence of 56.3% was
      seen in this study group. Higher incidence of hepatitis C was significantly
      associated with higher duration of dialysis. There was very little awareness
      among the nursing staff regarding dental care. CONCLUSION: There is greater
      deterioration of periodontal health among dialysis patients with chronic renal
      disease. Awareness regarding dental care is very less among patients undergoing
      renal dialysis. These patients should be monitored carefully to maintain their
      oral health. Awareness must be increased among dialysis patients and nursing
      staff about the need for primary prevention of dental diseases.

PMID- 25374835
TI  - Assessment of lip print patterns and its use for personal identification among
      the populations of Rajnandgaon, Chhattisgarh, India.
AB  - BACKGROUND: Personal identification plays an inevitable role in forensic
      investigation. Lip print is one of the evidences that can be left in the crime
      scene, which helps in identification purpose. Hence, the present study was
      undertaken to provide deeper inside view of use of cheiloscopy in personal
      identification, focusing on sex and age variability of lip print patterns in the
      population of Rajnandgaon city, Chhattisgarh, India. MATERIALS AND METHODS: The
      cross-sectional study was conducted among 200 (100 males and 100 females)
      subjects of age 15-55 years, residing in different areas of Rajnandgaon city. The
      sex of the individual was determined as per the description given by Vahanwala et
      al. Frequency distribution and Chi-square test were used for data analysis by
      SPSS 16.0 V software. RESULTS: The most common lip print pattern in entire
      population was Type I (27.5%). Very highly significant difference was found in
      the distribution of lip print patterns among males and females in the entire
      population, group I, and group III, respectively (P < 0.0001). The overall
      accuracy of cheiloscopy in sex determination was (high) 87.95%, 87.65%, 90.5%,
      and 80% in group 1, 2, 3, and 4, respectively. CONCLUSION: Thus, it can be
      concluded that lip prints can be used as one of the important forensic tools for
      personal identification on the basis of their age and gender variability among
      the populations.

PMID- 25374837
TI  - Exfoliative cytology of buccal squames: A quantitative cytomorphometric analysis
      of patients with diabetes.
AB  - BACKGROUND: Diabetes is a third leading cause of mortality and morbidity in the
      world. Diabetes is one of the most common endocrine metabolic disorders and its
      prevalence has been increasing worldwide. Oral exfoliative cytology may be a more
      appropriate adjunctive diagnostic tool in conditions like diabetes mellitus,
      where the invasive techniques lose viability. AIMS: The purpose of this study is
      to analyze the cytomorphometric changes in the exfoliated cells of the oral
      mucosa, as an adjunct to the diagnosis of diabetes. MATERIALS AND METHODS: Smears
      were taken from the buccal mucosa of 30 diabetes patients (study group) and 30
      healthy individuals (control group). All the smears were stained with rapid
      Papanicolaou stain (PAP). In the PAP smears, the nuclear area (NA), cytoplasmic
      area (CA), and cytoplasmic-to-nuclear ratio (CNR) were evaluated for 50 cells in
      each smear, using the Image Analysis Software (Magnus ProTM) and research
      microscope (Lawrence and MayoTM). RESULTS: The results showed that the mean NA
      was significantly higher (P < 0.001) in the study group, whereas, the mean CA did
      not exhibit a statistically significant difference (P > 0.001). The mean CNR was
      significantly lower in the study group (P < 0.001). INTERPRETATION AND
      CONCLUSION: The results associated with the clinical observations suggest that
      diabetes can produce morphological and functional alterations in the oral
      epithelial cells, detectable by microscopic and cytomorphometric analysis using
      exfoliative cytology, which can be used in the diagnosis of the disease.

PMID- 25374836
TI  - Effectiveness of supervised toothbrushing and oral health education in improving
      oral hygiene status and practices of urban and rural school children: A
      comparative study.
AB  - OBJECTIVE: To evaluate and compare the oral health status and the impact of
      supervised toothbrushing and oral health education among school children of urban
      and rural areas of Maharashtra, India. MATERIALS AND METHODS: A total of 200
      school children in the age group 12-15 years were selected by stratified random
      sampling technique from two schools and were further divided into two groups:
      Group A (urban school) and Group B (rural school). Both the groups were again
      subdivided into control group and study group. Supervised toothbrushing was
      recommended for both the groups. The toothbrushing teaching program included
      session on oral health education, individual toothbrushing instructions, and
      supervised toothbrushing. Dental caries increment, plaque scores, and gingival
      status were assessed as per the World Health Organization (WHO) criteria (1997),
      Turesky-Gilmore-Glickman modification of the Quigley Hein Plaque Index, and Loe
      Silness Gingival Index (1963), respectively. Cronbach's alpha, Chi-square test,
      paired t-test, and unpaired t-test were utilized for data analysis. RESULTS: The
      mean plaque and gingival score reduction was significantly higher in the study
      groups as compared to the control groups. An increase in the mean of Decayed,
      missing, filled teeth (DMFT) and Decayed, missing, filled teeth and surfaces
      (DMFS) scores throughout the study period was seen in children who participated
      in study. CONCLUSION: Oral health education was effective in establishing good
      oral health habits among school children and also in enhancing the knowledge of
      their parents about good oral health.

PMID- 25374838
TI  - Impact of caries prevalence on oral health-related quality of life among police
      personnel in Virajpet, South India.
AB  - OBJECTIVE: The objective of this study is to assess the impact of caries
      prevalence on oral health-related quality of life among police personnel in
      Virajpet, South India. MATERIALS AND METHODS: Police personnel were randomly
      selected from the 296 police staff working in Virajpet, India. They were invited
      for a dental examination and a questionnaire survey. A self-administered
      questionnaire was used to collect their demographic information, and to determine
      the oral health-related quality of life (OHRQoL). Caries experiences of the
      participants were recorded as per the World Health Organization (WHO) criteria
      (1997). The analysis of variance (ANOVA) was used to compare within-group
      differences of the selected sociodemographic factors and the Chi-square analysis
      was used to explore the association between the variables. RESULTS: All the 172
      invited participants joined this study. Their mean age was 38.02 +/- 9.08 years.
      There was no significant difference in oral health-related quality of life scores
      according to gender and age. The prevalence of dental caries was found to be 78%
      in the current study. Data analysis showed that there was no statistically
      significant association between the oral health-related quality of life scores
      and caries prevalence. CONCLUSION: The present study showed that there was no
      association between the oral health-related quality of life and caries prevalence
      among the police personnel in Virajpet.

PMID- 25374839
TI  - Comparison of root canal sealer distribution in obturated root canal: An in-vitro
      study.
AB  - BACKGROUND AND OBJECTIVES: Endodontic sealer is currently regarded with such
      importance in the root canal treatment that it is often considered to be more
      important than the core obturating material itself. Sealer with the least film
      thickness is favorable for minimizing microleakage. The aim of the study is to
      compare sealer distribution in root canal using three different sealers with
      three different obturation techniques. MATERIALS AND METHODS: AH plus, Fuji-1,
      Tubliseal Extended Working Time (EWT) was placed into the prepared root canals of
      90 maxillary central incisors using a lentulospiral. Thereafter, the canals were
      obturated using three different gutta-percha root filling techniques (single
      cone, lateral condensation, vertical condensation). Horizontal sectioning was
      carried out at 3 mm and 6 mm from the apex with a diamond disk. The two specimens
      thus obtained were examined for sealer distribution using a stereomicroscope and
      the percentage of sealer coating the perimeter (PSCP) was calculated using a
      digital imaging system. RESULTS: A significant difference existed in the mean
      PSCP values of three different sealers (P < 0.000), where Tubliseal (EWT) had the
      highest PSCP values followed by the AH plus and Fuji-1. Also, between techniques,
      differences were observed (P < 0.00), where a single cone technique had the
      highest mean values followed by lateral condensation and vertical condensation.
      Between the 3 mm and 6 mm sections a non-significant difference was observed (P <
      0.945). CONCLUSION: Tubliseal EWT showed highest PSCP value and Single cone
      technique showed the higher PSCP value then lateral and vertical condensation
      technique at 3 mm and 6 mm sections.

PMID- 25374840
TI  - IMRT with Stereotactic Body Radiotherapy Boost for High Risk Malignant Salivary
      Gland Malignancies: A Case Series.
AB  - Patients with high risk salivary gland malignancies are at increased risk of
      local failure. We present our institutional experience with dose escalation using
      hypofractionated stereotactic body radiotherapy (SBRT) in a subset of this rare
      disease. Over the course of 9 years, 10 patients presenting with skull base
      invasion, gross disease with one or more adverse features, or those treated with
      adjuvant radiation with three or more pathologic features were treated with
      intensity-modulated radiation therapy followed by hypofractionated SBRT boost.
      Patients presented with variable tumor histologies, and in all but one, the
      tumors were classified as poorly differentiated high grade. Four patients had
      gross disease, three had gross residual disease, three had skull base invasion,
      and two patients had rapidly recurrent disease (<=6 months) that had been
      previously treated with surgical resection. The median stereotactic radiosurgery
      boost dose was 17.5 Gy (range 10-30 Gy) given in a median of five fractions
      (range 3-6 fractions) for a total median cumulative dose of 81.2 Gy (range 73.2
      95.6 Gy). The majority of the patients received platinum based concurrent
      chemotherapy with their radiation. At a median follow-up of 32 months (range 12
      120) for all patients and 43 months for surviving patients (range 12-120),
      actuarial 3-year locoregional control, distant control, progression-free
      survival, and overall survival were 88, 81, 68, and 79%, respectively. Only one
      patient failed locally and two failed distantly. Serious late toxicity included
      graft ulceration in one patient and osteoradionecrosis in another patient, both
      of which underwent surgical reconstruction. Six patients developed fibrosis. In a
      subset of patients with salivary gland malignancies with skull base invasion,
      gross disease, or those treated adjuvantly with three or more adverse pathologic
      features, hypofractionated SBRT boost to intensity-modulated radiotherapy yields
      good local control rates and acceptable toxicity. 

PMID- 25374841
TI  - Measurement of mean cardiac dose for various breast irradiation techniques and
      corresponding risk of major cardiovascular event.
AB  - After breast conserving surgery, early stage breast cancer patients are currently
      treated with a wide range of radiation techniques including whole breast
      irradiation (WBI), accelerated partial breast irradiation (APBI) using high-dose
      rate (HDR) brachytherapy, or 3D-conformal radiotherapy (3D-CRT). This study
      compares the mean heart's doses for a left breast irradiated with different
      breast techniques. An anthropomorphic Rando phantom was modified with gelatin
      based breast of different sizes and tumors located medially or laterally. The
      breasts were treated with WBI, 3D-CRT, or HDR APBI. The heart's mean doses were
      measured with Gafchromic films and controlled with optically stimulated
      luminescent dosimeters. Following the model reported by Darby (1), major cardiac
      were estimated assuming a linear risk increase with the mean dose to the heart of
      7.4% per gray. WBI lead to the highest mean heart dose (2.99 Gy) compared to 3D
      CRT APBI (0.51 Gy), multicatheter (1.58 Gy), and balloon HDR (2.17 Gy) for a
      medially located tumor. This translated into long-term coronary event increases
      of 22, 3.8, 11.7, and 16% respectively. The sensitivity analysis showed that the
      tumor location had almost no effect on the mean heart dose for 3D-CRT APBI and a
      minimal impact for HDR APBI. In case of WBI large breast size and set-up errors
      lead to sharp increases of the mean heart dose. Its value reached 10.79 Gy for
      women with large breast and a set-up error of 1.5 cm. Such a high value could
      increase the risk of having long-term coronary events by 80%. Comparison among
      different irradiation techniques demonstrates that 3D-CRT APBI appears to be the
      safest one with less probability of having cardiovascular events in the future. A
      sensitivity analysis showed that WBI is the most challenging technique for
      patients with large breasts or when significant set-up errors are anticipated. In
      those cases, additional heart shielding techniques are required. 

PMID- 25374843
TI  - Immunotherapy for Lung Cancer: Has it Finally Arrived?
AB  - The possible link between infection/inflammation/immune activation and a cancer
      patient's outcome from both a causative and outcome point of view has long been
      postulated. Substantial progress in the understanding of tumor-associated
      antigens/epitopes, immune cellular subpopulations, cytokine pathways/expression,
      the tumor microenvironment, and the balance between tumor-immune suppression and
      stimulation have been made over the past decade. This knowledge has heralded a
      new era of tumor immunotherapy utilizing vaccines, immune checkpoint inhibition,
      and oncolytic viruses. Despite significant progress in the molecular era now with
      targeted therapeutics such as EGFR tyrosine kinase inhibitors and ALK fusion
      protein inhibitors that have significantly improved the outcome of these specific
      lung cancer subpopulations, the overall 5 year survival for all non-small cell
      lung cancer (NSCLC) is still <20%. Unlike malignancies such as malignant
      melanoma, renal cell carcinoma, and neuroblastoma given their documented
      spontaneous remission rates lung cancer historically has been felt to be
      resistant to immune approaches likely related to an immunosuppressive tumor
      microenvironment and/or lack of immune recognition. Defining responding
      populations, understanding the mechanism(s) underlying durable immune responses,
      and the role of chemotherapy, radiation, oncolytic viruses, and other tumor
      disrupting agents in augmenting immune responses have led to improved
      optimization of immune therapeutic strategies. The purpose of this review is to
      focus on the recent advances in lung immunotherapy with an emphasis on recent
      clinical trials in the last 5 years in NSCLC. 

PMID- 25374844
TI  - Improved irritative voiding symptoms 3 years after stereotactic body radiation
      therapy for prostate cancer.
AB  - BACKGROUND: Irritative voiding symptoms are common in elderly men and following
      prostate radiotherapy. There is limited clinical data on the impact of
      hypofractionated treatment on irritative voiding symptoms. This study sought to
      evaluate urgency, frequency, and nocturia following stereotactic body radiation
      therapy (SBRT) for prostate cancer. METHODS: Patients treated with SBRT
      monotherapy for localized prostate cancer from August 2007 to July 2011 at
      Georgetown University Hospital were included in this study. Treatment was
      delivered using the CyberKnife((r)) with doses of 35-36.25 Gy in five fractions.
      Patient-reported urinary symptoms were assessed using the International Prostate
      Symptom Score (IPSS) before treatment and at 1, 3, 6, 9, and 12 months post
      treatment and every 6 months thereafter. RESULTS: Two hundred four patients at a
      median age of 69 years received SBRT with a median follow-up of 4.8 years. Prior
      to treatment, 50.0% of patients reported moderate to severe lower urinary tract
      symptoms (LUTS) and 17.7% felt that urinary frequency was a moderate to big
      problem. The mean prostate volume was 39 cc and 8% had prior procedures for
      benign prostatic hyperplasia. A mean baseline IPSS-irritative (IPSS-I) score of
      4.8 significantly increased to 6.5 at 1 month (p < 0.0001), however returned to
      baseline at 3 months (p = 0.73). The IPSS-I score returned to baseline in 91% of
      patients by 6 months and 96% of patients by 2 years. Transient increases in
      irritative voiding symptoms were common at 1 year. The mean baseline IPSS-I score
      decreased to 4.4 at 24 months (p = 0.03) and 3.7 at 36 months (p < 0.0001). In
      men with moderate to severe LUTS (IPSS >= 8) at baseline, the mean IPSS-I
      decreased from a baseline score of 6.8-4.9 at 3 years post-SBRT. This decrease
      was both statistically (p < 0.0001) and clinically significant (minimally
      important difference = 1.45). Only 14.6% of patients felt that urinary frequency
      was a moderate to big problem at 3 years post-SBRT (p = 0.23). CONCLUSION:
      Treatment of prostate cancer with SBRT resulted in an acute increase in
      irritative urinary symptoms that peaked within the first month post-treatment.
      Irritative voiding symptoms returned to baseline in the majority of patients by 3
      months post-SBRT and were actually improved from baseline at 3 years post-SBRT.

PMID- 25374842
TI  - p53 Family and Cellular Stress Responses in Cancer.
AB  - p53 is an important tumor suppressor gene, which is stimulated by cellular stress
      like ionizing radiation, hypoxia, carcinogens, and oxidative stress. Upon
      activation, p53 leads to cell-cycle arrest and promotes DNA repair or induces
      apoptosis via several pathways. p63 and p73 are structural homologs of p53 that
      can act similarly to the protein and also hold functions distinct from p53. Today
      more than 40 different isoforms of the p53 family members are known. They result
      from transcription via different promoters and alternative splicing. Some
      isoforms have carcinogenic properties and mediate resistance to chemotherapy.
      Therefore, expression patterns of the p53 family genes can offer prognostic
      information in several malignant tumors. Furthermore, the p53 family constitutes
      a potential target for cancer therapy. Small molecules (e.g., Nutlins, RITA,
      PRIMA-1, and MIRA-1 among others) have been objects of intense research interest
      in recent years. They restore pro-apoptotic wild-type p53 function and were shown
      to break chemotherapeutic resistance. Due to p53 family interactions small
      molecules also influence p63 and p73 activity. Thus, the members of the p53
      family are key players in the cellular stress response in cancer and are expected
      to grow in importance as therapeutic targets. 

PMID- 25374845
TI  - Staphylococcus aureus small colony variants show common metabolic features in
      central metabolism irrespective of the underlying auxotrophism.
AB  - In addition to the classical phenotype, Staphylococcus aureus may exhibit the
      small colony-variant (SCV) phenotype, which has been associated with chronic,
      persistent and/or relapsing infections. SCVs are characterized by common
      phenotypic features such as slow growth, altered susceptibility to antibiotic
      agents and pathogenic traits based on increased internalization and intracellular
      persistence. They show frequently auxotrophies mainly based on two different
      mechanisms: (i) deficiencies in electron transport as shown for menadione- and/or
      hemin-auxotrophs and (ii) thymidylate biosynthetic-defective SCVs. To get a
      comprehensive overview of the metabolic differences between both phenotypes, we
      compared sets of clinically derived menadione-, hemin- and thymidine-auxotrophic
      SCVs and stable site directed mutants exhibiting the SCV phenotype with their
      corresponding isogenic parental strains displaying the normal phenotype.
      Isotopologue profiling and transcriptional analysis of central genes involved in
      carbon metabolism, revealed large differences between both phenotypes. Labeling
      experiments with [U-(13)C6]glucose showed reduced (13)C incorporation into
      aspartate and glutamate from all SCVs irrespective of the underlying
      auxotrophism. More specifically, these SCVs showed decreased fractions of (13)C2
      aspartate and glutamate; (13)C3-glutamate was not detected at all in the SCVs. In
      comparison to the patterns in the corresponding experiment with the classical S.
      aureus phenotype, this indicated a reduced carbon flux via the citric acid cycle
      in all SCV phenotypes. Indeed, the aconitase-encoding gene (acnA) was found down
      regulated in all SCV phenotypes under study. In conclusion, all SCV phenotypes
      including clinical isolates and site-directed mutants displaying the SCV
      phenotype were characterized by down-regulation of citric acid cycle activity.
      The common metabolic features in central carbon metabolism found in all SCVs may
      explain similar characteristics of the S. aureus SCVs irrespective of their
      auxotrophism as well as the specific genetic and/or regulatory backgrounds. 

PMID- 25374846
TI  - Metabolic aspects of bacterial persisters.
AB  - Persister cells form a multi-drug tolerant subpopulation within an isogenic
      culture of bacteria that are genetically susceptible to antibiotics. Studies with
      different Gram negative and Gram positive bacteria have identified a large number
      of genes associated with the persister state. In contrast, the revelation of
      persister metabolism has only been addressed recently. We here summarize
      metabolic aspects of persisters, which includes an overview about the
      bifunctional role of selected carbohydrates as both triggers for the exit from
      the drug tolerant state and metabolites which persisters feed on. Also alarmones
      as indicators for starvation have been shown to influence persister levels via
      different signaling cascades involving the activation of toxin-antitoxin systems
      and other regulatory factors. Finally, recent data obtained by (13)C-isotopolog
      profiling demonstrated an active amino acid anabolism in Staphylococcus aureus
      cultures challenged with high drug concentrations. Understanding the metabolism
      of persister cells poses challenges but also paves the way for the development of
      anti-persister compounds. 

PMID- 25374848
TI  - Role of Family Medicine Education in India's Step Toward Universal Health
      Coverage.
AB  - India's commitment to universal health coverage has grown stronger with the
      submission of High Level Expert Group report by the Planning Commission in 2012.
      With this report comes the commitment to increase the primary health-care
      workforce to meet the population needs. However, the focus should not be just to
      increase the number of health workers, but to produce better health workers.
      Doctors, nurses and community health workers trained in primary and secondary
      health-care facilities can make a significant contribution in responding to the
      needs of the local community. The role of family medicine education is worth
      exploring in this context to equip the primary care health workers with the
      competencies of providing person-centered, comprehensive and continuous care. 

PMID- 25374847
TI  - Beyond controversies: sexuality education for adolescents in India.
AB  - Sexuality education for adolescents is one of the most controversial topics in
      the field of child health. In the past decade, policymakers in India have also
      struggled with the issue and there has been greater public discourse. However,
      policymaking and public discussions on adolescent sexuality education are
      frequently fueled by religious, social, and cultural values, while receiving
      scant scientific attention. To meet the needs of an expanding young population in
      India, scientific evidence for best practices must be kept at the core of
      policymaking in the context of sexuality education for adolescents. 

PMID- 25374849
TI  - Can credit systems help in family medicine training in developing countries? An
      innovative concept.
AB  - There is irrefutable evidence that health systems perform best when supported by
      a Family Physician network. Training a critical mass of highly skilled Family
      Physicians can help developing countries to reach their Millennium Development
      Goals and deliver comprehensive patient-centered health care to their population.
      The challenge in developing countries is the need to rapidly train these Family
      Physicians in large numbers, while also ensuring the quality of the learning, and
      assuring the quality of training. The experience of Christian Medical College
      (CMC), Vellore, India and other global examples confirm the fact that training
      large numbers is possible through well-designed blended learning programs. The
      question then arises as to how these programs can be standardized. Globally, the
      concept of the "credit system" has become the watch-word for many training
      programs seeking standardization. This article explores the possibility of
      introducing incremental academic certifications using credit systems as a method
      to standardize these blended learning programs, gives a glimpse at the innovation
      that CMC, Vellore is piloting in this regard partnering with the University of
      Edinburgh and analyses the possible benefits and pitfalls of such an approach. 

PMID- 25374850
TI  - Why genetically modified food need reconsideration before consumption?

PMID- 25374851
TI  - Food for thought.

PMID- 25374852
TI  - Intimate Partner Violence and Associated Coping Strategies among Women in a
      Primary Care Clinic in Port Harcourt, Nigeria.
AB  - CONTEXT: Intimate partner violence (IPV) is an important gender-based, social,
      and public health problem, affecting women globally. AIMS: The aim was to report
      the prevalence of IPV and describe the coping strategies of the victims. SETTINGS
      AND DESIGN: It was conducted in the general outpatient clinic of a tertiary care
      hospital using a cross-sectional design. MATERIALS AND METHODS: A random sample
      of consenting women living in an intimate partnership for a minimum of 1 year
      were served with a three part structured questionnaire which sought information
      on sociodemographic characteristics, the experience of IPV and the Brief COPE
      Inventory. STATISTICAL ANALYSIS USED: SPSS version 17.0 software, Microsoft word
      and Excel were used in data handling and analysis. Means, percentages, standard
      deviations, and Chi-square were calculated. P < 0.05 was considered to be
      significant. RESULTS: Of the 384 participants, 161 (41.9%) were physically
      abused. IPV was significantly common among women <=40 years of age, married
      couples (78.5%), unemployed and in Christians. It was precipitated by argument
      with husband (19.25%) and financial demands (44.10%). The employed coping
      strategy with the highest score was religion. The least score was found in
      substance abuse. CONCLUSION: There was significantly high prevalence of domestic
      violence against women in this study. Hence, routine screening is advocated by
      family physicians to elicit abuse in order to avoid the more devastating
      psychological consequences after the incidence so as to institute appropriate
      treatment as multiple episodes of abuse appears to be cumulative in effect. The
      reason for violence mainly borders around the argument with husband and finance
      issues. The coping strategies utilized by the participants minimally involve
      substance abuse, but more of a religion.

PMID- 25374853
TI  - Tobacco Smoking Status as Assessed by Oral Questionnaire Results 30% Under
      reporting by Adult Males in Rural India: A Confirmatory Comparison by Exhaled
      Breath Carbon Monoxide Analysis.
AB  - BACKGROUND: The authenticity and true status of tobacco use, especially in the
      form of smoking among the patient clientele is always a matter of concern for
      their physicians. OBJECTIVES: The purpose of this study was to assess the
      authenticity of self-reported habit of tobacco smoking among a population sample
      of male respondents in rural India. METHODS: Respondents were asked to complete
      oral questionnaires that assessed their status of tobacco smoking (if any) as
      well as duration of tobacco smoking, type of tobacco smoking, and frequency of
      tobacco smoking. Subsequently, exhaled breath carbon monoxide analysis was
      performed to detect their amounts of exhaled carbon monoxide. RESULTS: In 175
      respondents, the Smoke Check color indicators were significantly different (P <
      0.0001) in the respondents who were diagnosed smokers per oral questionnaires (n
      = 92) versus diagnosed nonsmokers per oral questionnaires (n = 83). The
      probability statistics of authenticity of oral questionnaires for assessing
      smoking status showed that self-reporting was only 75% sensitive and 76% specific
      with 80% positive predictive value and 70% negative predictive value. CONCLUSION:
      True status of tobacco smoking with exhaled breath carbon monoxide analysis can
      be an easy clinical maneuver with community health screening and health promotion
      implications among patient populations in rural India.

PMID- 25374854
TI  - Knowledge of common problems of newborn among primi mothers admitted in a
      selected hospital for safe confinement.
AB  - BACKGROUND: Among the almost 3.9 million newborn deaths that occur worldwide,
      about 30% occur in India. Children are our future and utmost precious resources.
      After birth the health of the child depends upon the health care practice adopted
      by the family, especially by the mothers. Information about neonatal problems and
      newborn care practices will help in reducing mortality and morbidity during the
      neonatal period. This study was conducted to identify the knowledge of primi
      mothers with regard to the common problems of normal neonates. MATERIALS AND
      METHODS: This descriptive study was carried out among the mothers of neonates in
      the Maternity Unit of a Medical College Hospital in Mangalore. A pretested
      structured knowledge questionnaire was used to collect information from 60 primi
      mothers, who were admitted for safe confinement for a one-month period. RESULTS:
      The findings of the study show that the majority, that is, 27 (45%) of the primi
      mothers had a good knowledge of all the areas such as vomiting, regurgitation,
      diaper rash, umbilical cord infection, fever, constipation, and diarrhea. About
      20 (33.3%) had very good knowledge and about 13 (21.67%) had an average level of
      knowledge on the common problems of newborns. Knowledge about vomiting was
      average among 34 (56.67%), poor in 21 (35%), and good in five (8.33%). Knowledge
      about diaper rash was average among 36 (60%), good among 21 (35%), and poor among
      three (5%). Knowledge on umbilical cord infection was average in 29 (48.33%),
      good in 27 (45%), and poor in 4 (6.67%). Knowledge on fever was good in 38
      (63.33%), average in 19 (31.66%), and poor in three (5%). Knowledge on
      constipation and diarrhea were average in 38 (63.34%), good in 11 (18.33%), and
      poor in 11 (18.33%). No association was found between the knowledge of primi
      mothers and selected baseline variables, such as, age, education, religion,
      occupation, type of family or area of dwelling. CONCLUSION: The study concludes
      that there is a need to provide adequate information to first-time mothers about
      common newborn problems and this will help mothers care for their newborns
      better.

PMID- 25374855
TI  - Therapeutic-diagnostic Evaluation of Chronic Cough Amongst Adults: Causes,
      Symptoms and Management at the Primary Care Level, Malaysia.
AB  - BACKGROUND: Patients presenting with chronic cough pose a common diagnostic
      dilemma during routine consultations at public primary care clinics in Malaysia.
      To date, there has been little attempt at designing a standardized model or
      algorithm to facilitate an accurate diagnosis of chronic cough. This study
      proposes a clinical method to detect the causes of chronic cough in a primary
      care setting in Malaysia. MATERIALS AND METHODS: A total of 117 patients aged
      above 18 at an urban primary care clinic were tracked over a span of 5 months to
      diagnose the cause of chronic cough. A therapeutic-diagnostic method was employed
      to help identify the causes of chronic cough. Subsequently, the demographic
      details of patients, the prevalence of the different causes of chronic cough and
      the relationship between history and diagnosis were analyzed statistically.
      RESULTS: Chronic cough had a slightly higher male preponderance (51.3% vs.
      48.7%). Patients within the 'above 60' age category had the highest frequency of
      chronic cough. The most common cause of chronic cough was post-infectious cough
      (n = 42, 35.9%), followed closely by angiotensin-converting enzyme-inhibitor
      related cough (n = 14, 12%). Majority of patients had the symptom of phlegm
      production (n = 41, 54%). 33 patients (29.2%) had recent upper respiratory tract
      infection (<2 weeks ago) prior to the diagnosis of chronic cough. There were poor
      association between symptoms and the various entities comprising chronic cough.
      The exceptions were the following associations: (1) Bronchial asthma and
      itchiness of throat (P = 0021), (2) gastroesophageal reflux disease and heartburn
      (P < 0.001), (3) upper airway cough syndrome and running nose (P = 0.016) and (4)
      pulmonary tuberculosis and absence of weight loss (P = 0.004). CONCLUSION: This
      study demonstrates that the effectiveness of a therapeutic-diagnostic technique
      in the diagnosis of chronic cough. Consistent with previous studies, there was
      poor association between most symptoms and the causes of chronic cough. A study
      involving a larger primary care population is required to confirm the findings
      found in this analysis.

PMID- 25374856
TI  - Tracking the implementation to identify gaps in integrated disease surveillance
      program in a block of district jhajjar (haryana).
AB  - CONTEXT: To strengthen the surveillance system in India, Integrated Disease
      Surveillance Program (IDSP) was launched in 2004. The frequent occurrence of
      epidemics even after the launching of the IDSP was an indication toward
      inadequacy of the system. The responsibility for effective implementation of IDSP
      at the sub-center level lies with the health workers. AIMS: The aim of the
      following study was to assess the knowledge and practice of health workers
      regarding IDSP and to assess the quality of IDSP reports at the sub-center level.
      SETTINGS AND DESIGN: It was cross-sectional study carried out in the area under
      Community Health Center Dighal which is the rural field practice area attached to
      Post Graduate Institute of Medical Sciences, Rohtak in the State of Haryana,
      India. SUBJECTS AND METHODS: All the 24 sub-centers in the area were visited and
      46 health workers (22 male; 24 female) who met the inclusion criteria i.e. who
      had completed 1 year of their service or had been trained for IDSP, were included
      in the study. Data were collected on a self-designed, semi-structured and pre
      tested schedule by interviewing the study subjects and observation of the
      records/reports. STATISTICAL ANALYSIS USED: Percentages and proportions. RESULTS:
      Only 14/46 (~30%) of the workers could expand the abbreviation "IDSP" correctly.
      Only 4/46 (~9%) workers could narrate any of the trigger events and none could
      tell all the trigger events. Only at 12 such sub-centers, diagnoses were being
      written in their out-patient registers according to the defined syndromes. 43/46
      (~93%) workers were not aware of the zero reporting. CONCLUSIONS: The
      surveillance system is much less alert and intense than the desired level and
      needs to be strengthened.

PMID- 25374857
TI  - Data Entry Skills in a Computer-based Spread Sheet Amongst Postgraduate Medical
      Students: A Simulation Based Descriptive Assessment.
AB  - BACKGROUND: In India, research work in the form of a thesis is a mandatory
      requirement for the postgraduate (PG) medical students. Data entry in a computer
      based spread sheet is one of the important basic skills for research, which has
      not yet been studied. This study was conducted to assess the data entry skills of
      the 2(nd) year PG medical students of a medical college of North India. MATERIALS
      AND METHODS: A cross-sectional, descriptive study was conducted among 111 second
      year PG students by using four simulated filled case record forms and a computer
      based spread sheet in which data entry was to be carried out. RESULTS: On a scale
      of 0-10, only 17.1% of the students scored more than seven. The specific sub
      skills that were found to be lacking in more than half of the respondents were as
      follows: Inappropriate coding (93.7%), long variable names (51.4%), coding not
      being done for all the variables (76.6%), missing values entered in a non-uniform
      manner (84.7%) and two variables entered in the same column in the case of blood
      pressure reading (80.2%). CONCLUSION: PG medical students were not found to be
      proficient in data entry skill and this can act as a barrier to do research. This
      being a first of its kind study in India, more research is needed to understand
      this issue and then include this yet neglected aspect in teaching research
      methodology to the medical students.

PMID- 25374858
TI  - Spectrum of hemoglobin variants in the population of northern region of west
      bengal: an ethnogenetic proposition.
AB  - CONTEXT: The birth of transfusion-dependent states of hemoglobinopathies
      including thalassemias is preventable by population screening and genetic
      counseling. Magnitude is not addressed in the Northern Region of West Bengal
      where many ethnic variants inhabit. AIMS AND OBJECTIVES: The aim of the following
      study is to find out the burden of different entities of hemoglobinopathies,
      their correlation with ethnicity and the "at risk" groups. SUBJECTS AND METHODS:
      A descriptive study was conducted from the Hematology Unit of North Bengal
      Medical College over 1 year on the subjects underwent screening for
      hemoglobinopathies for detection of abnormal hemoglobin (Hb) variants by "cation
      exchange high-performance liquid chromatography" principle along with other
      relevant tests. STATISTICAL ANALYSIS: Data was analyzed by frequency distribution
      and Chi-square test assuming P value as 95% of the level of significance using
      the SPSS version 16 (SPSS Inc., Chicago, Illinois, U.S.A). RESULT: Abnormal Hb
      variant was 47.5% among 1872. Hb E trait (34.4%) was most common followed by Hb E
      disease (25.3%) and others. Hb E disorders (92.7%) were observed mostly among
      Rajbangsi population while E-beta-thalassemias (40%) in the Muslims and a
      heterogeneous pattern noted among tribal and mongoloid. CONCLUSION: Hb E
      hemoglobinopathies was high among Rajbangsi and Muslims with identification of
      some other hemoglobinopathies involving tribal and mongoloid.

PMID- 25374859
TI  - Beliefs About Medicines and Self-reported Adherence Among Patients with Chronic
      Illness: A Study in Palestine.
AB  - BACKGROUND: Identifying factors associated with adherence is of great value in
      clinical practice. The objective of this study was to investigate medication
      adherence, beliefs about medicines held by people with chronic illness and
      whether beliefs influence medication adherence. METHODS: The study was carried
      out at primary health care clinic of the Palestinian Medical Military Services in
      Nablus, Palestine. The beliefs about medicines questionnaire was used to assess
      beliefs and Morisky medication adherence scale was used to assess adherence.
      RESULTS: A total of 187 patients were interviewed. Most participants (79.6%)
      agreed or strongly agreed that their medications were necessary for their current
      health. However, 58.2% of the participants were concerned about having to take
      their medicines on a regular basis and 57.8% were concerned about becoming
      dependent on their medicines. None of the demographic and clinical variables was
      significantly associated with medication adherence. However, multivariate
      analysis showed that patients who had higher beliefs about medication necessity
      had higher odds (1.107 [1.023-1.197]) of being adherent. On the other hand,
      patients who had higher concern beliefs had lower odds (0.908 [0.845-0.975]) of
      being adherent. CONCLUSIONS: Beliefs about medicines are a major contributing
      factor to medication adherence.

PMID- 25374860
TI  - Attitudes toward Euthanasia and Related Issues among Physicians and Patients in a
      Multi-cultural Society of Malaysia.
AB  - INTRODUCTION: Due to globalization and changes in the health care delivery
      system, there has been a gradual change in the attitude of the medical community
      as well as the lay public toward greater acceptance of euthanasia as an option
      for terminally ill and dying patients. Physicians in developing countries come
      across situations where such issues are raised with increasing frequency. As
      euthanasia has gained world-wide prominence, the objectives of our study
      therefore were to explore the attitude of physicians and chronically ill patients
      toward euthanasia and related issues. Concomitantly, we wanted to ascertain the
      frequency of requests for assistance in active euthanasia. MATERIALS AND METHODS:
      Questionnaire based survey among consenting patients and physicians. RESULTS: The
      majority of our physicians and patients did not support active euthanasia or
      physician-assisted suicide (EAS), no matter what the circumstances may be P <
      0.001. Both opposed to its legalization P < 0.001. Just 15% of physicians
      reported that they were asked by patients for assistance in dying. Both
      physicians 29.2% and patients 61.5% were in favor of withdrawing or withholding
      life-sustaining treatment to a patient with no chances of survival. Among
      patients no significant differences were observed for age, marital status, or
      underlying health status. CONCLUSIONS: A significant percentage of surveyed
      respondents were against EAS or its legalization. Patient views were primarily
      determined by religious beliefs rather than the disease severity. More debates on
      the matter are crucial in the ever-evolving world of clinical medicine.

PMID- 25374861
TI  - Dimensions of quality of antenatal care sservice at suez, egypt.
AB  - INTRODUCTION: The 5(th) millennium development goal aims at reducing maternal
      mortality by 75% by the year 2015. According to the World Health Organization,
      there was an estimated 358,000 maternal deaths globally in 2008. Developing
      countries accounted for 99% of these deaths of which three-fifths occurred in Sub
      Saharan Africa. In primary health care (PHC), quality of antenatal care is
      fundamental and critically affects service continuity. Nevertheless, medical
      research ignores the issue and it is lacking scientific inquiry, particularly in
      Egypt. AIM OF THE STUDY: The aim of the following study is to assess the quality
      of antenatal care in urban Suez Governorate, Egypt. MATERIALS AND METHODS: A
      cross-sectional primary health care center (PHCC) based study conducted at five
      PHCC in urban Suez, Egypt. The total sample size collected from clients,
      physicians and medical records. Parameters assessed auditing of medical records,
      assessing provider and pregnant women satisfaction. RESULTS: Nearly 97% of
      respondents were satisfied about the quality of antenatal care, while provider's
      satisfaction was 61% and for file, auditing was 76.5 +/- 5.6. CONCLUSION: The
      present study shows that client satisfaction, physicians' satisfaction and
      auditing of medical record represent an idea about opportunities for improvement.

PMID- 25374862
TI  - Radiation safety of women of the reproductive age: evaluation of the role of
      referring physicians.
AB  - BACKGROUND: Women between 12 and 50 years are in the reproductive age. The
      likelihood of or actual presence of pregnancy should be ruled out before they are
      exposed to medical ionizing radiation. Fetal exposure to ionizing radiation can
      either induce malformation (teratogenic) or cancer. They should be exposed only
      when it is safe for the fetus or when the benefit far outweighs the risk in
      urgent medical conditions. The radiation dose in medical imaging is generally
      below the threshold to induce malformation (100 mGy) in the fetus, but there is
      indeed no safe level as the risk of cancer induction later in life can occur at
      any dose. The referring physician must obtain the last menstrual period (LMP) and
      sometimes carry out pregnancy test before sending their patients for examinations
      using ionizing radiation. However, there are circumstances in which these rules
      are waived. OBJECTIVE: The purpose of the study is to evaluate the role of the
      referring physician in the radiation protection of the fetus using the LMP.
      SUBJECTS AND METHODS: This is a prospective study over a 2-month period. All the
      request forms of menstruating women aged 12-50 years sent for conventional
      radiography are included in the study. RESULTS: One percent provided the LMP in
      the request forms. 0.6% (one) of our subjects was sure she is pregnant, but 13.7%
      (25) had an overdue menstruation. CONCLUSION: The level of compliance of the
      physicians with the referral guidelines for women of reproductive age is poor.

PMID- 25374863
TI  - Prevalence of Folate, Ferritin and Cobalamin Deficiencies amongst Adolescent in
      India.
AB  - BACKGROUND: In India, 60-90% of adolescent suffer from anemia. Studies have
      documented folate, ferritin, and cobalamin deficiencies to be the major causes of
      nutritional anemia. However, limited data is available on the prevalence of
      folate, ferritin, and cobalamin deficiencies amongst adolescent from India.
      OBJECTIVES: The present study was carried out to find out the magnitude of
      folate, ferritin, and cobalamin deficiencies amongst adolescent of 11-18 years of
      age in National Capital Territory (NCT) of Delhi, India. MATERIALS AND METHODS: A
      cross-sectional, school-based study was conducted in NCT of Delhi, India in the
      year 2010-2011. About 347 adolescent belonging to low- (LIG), middle- (MIG), and
      high-income groups (HIG) were selected using the probability proportionate to
      size (PPS) sampling methodology. Serum ferritin, serum folate, and serum
      cobalamin levels were determined by the enzyme-linked immunosorbent assay (ELISA)
      method, radioimmunoassay (RIA) method, and radioisotopic method, respectively.
      Hemoglobin (Hb) estimation was done by cyanmethemoglobin method in all the blood
      samples collected. RESULTS: The prevalence of deficiency of ferritin in HIG, MIG,
      and LIG categories of adolescent was found to be 52.9, 67, and 58.8%,
      respectively. In the HIG, MIG, and LIG categories of adolescent, the prevalence
      of folate deficiency was 22.5, 40.4, and 52.2%, respectively. The prevalence of
      deficiency of cobalamin in HIG, MIG, and LIG categories of adolescent was 47.1,
      80.7 and 87.5%, respectively. About 48, 66.1, and 68.4% of adolescent in the HIG,
      MIG, and LIG categories, respectively had Hb levels less than 12 g/dL and were
      found to be suffering from anemia. CONCLUSIONS: A high prevalence of anemia
      existed along with deficiency of ferritin, cobalamin, and folate amongst
      adolescent. The strategies for prevention of anemia amongst adolescent in India
      should also include cobalamin along with iron and folate supplementation for
      prevention and control of nutritional anemia. Primary care physicians should
      suspect all the three causes for anemia.

PMID- 25374864
TI  - Study of drug utilization pattern for acute exacerbation of chronic obstructive
      pulmonary disease in patients attending a government hospital in kerala, India.
AB  - OBJECTIVE: Drug utilization studies are powerful exploratory tools to ascertain
      the role of drugs in society. This study was conducted to establish the drug
      utilization pattern and the common adverse drug reactions for the treatment of
      acute exacerbation of chronic obstructive pulmonary disease (COPD) in one of the
      government hospitals in Kerala, India. METHODS: This was a prospective
      observational study aimed at recognizing the drug utilization pattern for the
      treatment of acute exacerbation of COPD for 7-day under nonexperimental settings.
      All information significant to the study was collected from the case records and
      discussions conducted with the inpatients and bystanders during ward rounds, with
      the support of a physician. Moreover, daily follow-ups were conducted to assemble
      data on amendment in therapy, add-on therapy, and clinical improvement until the
      patient was discharged from the hospital or to an upper limit of 7-day, whichever
      is earlier. RESULTS: All the patients in this study received combination therapy.
      Among the inhalational beta-agonists, salbutamol accounted for 74% use.
      Parenteral steroids were used in 78% of the patients and all of them received
      hydrocortisone. Steroid inhalers were used only in 25% of the patients.
      Anticholinergics were used in 77.5% of patients. Antibiotics were used in 86.7%
      patients. The main adverse effects noted were dry mouth (15%) and bad taste (10%)
      and these adverse effects were highly correlated with the use of anticholinergics
      (P < 0.05). CONCLUSIONS: Despite the use of drugs according to the availability
      and physician's preference, it was found in the analysis that majority were in
      accordance with Global Initiative for Chronic Obstructive Lung Disease criteria
      recommendations.

PMID- 25374865
TI  - Cardiovascular Disease Risk Factor Profiling of Group C Employees in JIPMER,
      Puducherry.
AB  - BACKGROUND: Settings-based approach for health promotion includes conducting risk
      factor surveillance as one of its component. It was aimed to estimate the
      prevalence of CVD risk factors among group C employees of tertiary care hospital
      in south India. MATERIALS AND METHODS: A cross-sectional survey was conducted
      among 400 group C employees aged >=20 years using the WHO "STEPwise approach to
      surveillance of non-communicable diseases" (STEPS) methodology. Standardized
      international protocols were used to measure behavioral risk factors (smoking,
      alcohol consumption, fruit and vegetable consumption, physical activity) and
      physical characteristics (weight, waist and hip circumferences, height, and blood
      pressure). Multivariate analysis was done to predict the factors, which carry
      independent risk of hypertension. Risk factor profiling of the staff was done
      using WHO/ISH risk prediction chart to calculate the 10-year risk of a fatal or
      non-fatal major cardiovascular events (myocardial infarction or stroke),
      according to age, gender, blood pressure, smoking status, and presence or absence
      of diabetes mellitus. RESULTS: Mean age in years was 40.9 (+/-10.4), and men
      constituted 81.3% of study population. Prevalence of major cardiovascular risk
      factors was as follows: Current smokers 12.3% men, regular alcohol intake 33.2%
      among men, overweight (>=23 kg/m(2)) 74.5%, central obesity 78.7%, hypertension
      38.8%, and history of diabetes mellitus 13.2%. Age, gender, physical inactivity,
      obesity, and family history of hypertension were found to be independently
      associated with hypertension. Four percent participants had a >10% risk of
      developing CVD in next 10 years. CONCLUSION: The prevalence of CVD risk factors
      is high in the sample population. Employee wellness program should be started in
      the institute to combat the burden of cardiovascular diseases.

PMID- 25374866
TI  - Beers criteria-based assessment of medication use in hospitalized elderly
      patients in southern Brazil.
AB  - BACKGROUND: Population aging has evolved gradually. Polypharmacy to control
      disease associated with age-related physiological changes increases the risk of
      adverse drug reactions, including drug interactions among the elderly population.
      OBJECTIVE: This study was intended to assess the medications used by the elderly
      population, aiming at identifying the potentially inappropriate medications
      according to the Beers Criteria. MATERIALS AND METHODS: We conducted a cross
      sectional study on medical records to assess the use of medications by elderly
      patients admitted to the Hospital Nossa Senhora da Conceicao in 2011. The
      variables included gender, age, reasons for admission, comorbidities, and
      medications used by the elderly patients. RESULTS: In total, we reviewed 440
      medical records. Patients were predominantly male (51.6%). The total number of
      medications used was 5904, with an average of 13.4 per person. The three most
      commonly used drugs were dipyrone, omeprazole, and metoclopramide. The most
      frequently used drugs according to the Anatomical Therapeutic Chemical
      Classification (ATC) system were those of the alimentary tract and metabolism,
      nervous system, and cardiovascular system. Of the 255 types of drugs used, 42
      (16.4%) were included in the Beers list, and the three most often used were
      metoclopramide, ketoprofen, and aspirin. CONCLUSION: The number of medications
      used per patient was substantial, and potentially inappropriate medications
      according to the Beers Criteria were significant as well.

PMID- 25374867
TI  - Primary hypoparathyroidism presenting with new adult onset seizures in family
      practice.
AB  - Hypoparathyroidism commonly presents with paresthesias, fatigue, anxiety, muscle
      cramps and infrequently with seizures due to hypocalcaemia. Here, we present a
      case of 27-year-old adult female presenting with new onset convulsions who was
      subsequently diagnosed to have primary (congenital) hypoparathyroidism. 

PMID- 25374868
TI  - Insulin injection site dystrophic calcification with fat necrosis: a case report
      of an uncommon adverse effect.
AB  - We report a case of an uncommon adverse effect of insulin injection resulting in
      hard subcutaneous swelling in the lower abdomen of a 47-year-oldfemale with type
      1 diabetes. Extensive dystrophic calcification and fat necrosis was revealed on
      histopathological examination. 

PMID- 25374869
TI  - Losartan-induced Ischemic Hepatocellular Hepatotoxicity: A Case Report and
      Literature Review.
AB  - With the increasing use of various medications and supplements nowadays, the
      incidence of abnormal liver function tests and frank hepatic injury is has been
      increasing. Medications are now considered one of the most common causes of acute
      hepatic failure in the United States. Losartan was the first angiotensin 1 (AT1)
      receptor blocker approved by FDA for the treatment of arterial hypertension. It
      is a well-tolerated medication with few significant adverse effects. However,
      losartan-related hepatotoxicity has been reported rarely. We report a case of
      acute hepatic injury in an adult patient treated with losartan as a monotherapy
      for arterial hypertension. 

PMID- 25374870
TI  - Johnson-McMillin Microtia Syndrome: New Additional Family.
AB  - Microtia is a congenital anomaly that is found with different prevalence among
      various populations. The exact etiology of ear anomalies is still unknown. We
      describe a new additional family with this rare disorder; Johnson-McMillin
      syndrome (JMS) where mother, son, and distant grandmother have multiple features
      of JMS in the form of microtia, facial asymmetry, ear malformation, hearing
      defect, and hypotrichosis. Variable presentations in this family could be
      referred to phenotype variation supporting an autosomal dominant pattern of
      inheritance. We observed that the mother was very sad and suffered from feelings
      of guilt. We found that she had isolated herself from family and community out of
      fear of being stigmatized and hurt. We concluded that the occurrence of microtia
      is of public health importance, adhering to traditional marriage customs in Egypt
      increases women's risk of giving birth to a disabled child, yet the mothers are
      blamed and shamed for their children's birth defects by their husbands, families,
      and communities, while the fathers are not stigmatized. 

PMID- 25374871
TI  - An Unusual Case of Primary Human Immunodeficiency Virus Infection Presenting as
      Mononucleosis-like Syndrome and Acute Aseptic Meningoencephalitis. Report of a
      Case and Review of the Literature.
AB  - Clinical presentation of primary human immunodeficiency virus (HIV) infection
      includes a wide spectrum of manifestations from asymptomatic infection to a
      symptomatic and severe illness. Central nervous system involvement should be
      always considered as a severe clinical form of primary HIV infection. Physicians
      should be aware to the broad clinical spectrum of primary HIV infection. We
      report a case of a female with diagnosis of mononucleosis-like syndrome and acute
      aseptic meningoencephalitis during primary HIV infection. 

PMID- 25374872
TI  - Dysmorphism in One of a Set of Male Twins; Could They have been Identical Twins?
      A Diagnostic Dilemma.
AB  - Twinning occurs worldwide, but Nigerian women of the southwest extraction record
      one of the highest rates in the world. Among the notable risk factors for
      fraternal twinning is advanced maternal age, which is also an independent risk
      factor for Down syndrome. Even as morphological characteristics can easily be
      applied to distinguish identical from fraternal twins, in cases of an associated
      dysmorphism, in any member of the couplet, it becomes a difficult tool to use, as
      has been observed in the case of a set of twins who were of the same sex, blood
      group, hemoglobin genotype, and shared the same placenta. 

PMID- 25374873
TI  - Hashimoto's Encephalitis: Unusual Cause of Reversible Dementia.
AB  - Hashimoto's encephalopathy (HE) is a poorly understood and often misdiagnosed
      rare autoimmune disease with varied neurological and psychiatric features. The
      low prevalence and varied clinical features coupled with unclear pathogenesis and
      histopathologic characteristics have caused still doubts in any particular
      diagnostic criteria. Therefore, more case studies are needed to characterize the
      clinical, laboratory and imaging features and outcomes of HE patients. We
      describe a case of such a patient with HE presenting with dementia and focus on
      its early recognition as the cognitive changes are reversible. 

PMID- 25374874
TI  - Sudden cardiac death, aborted, in healthy 34-year-old male.
AB  - A 34-year-old male, non-hypertensive, non-diabetic, had a sudden onset of cardiac
      arrest, he was revived and then referred to a cardiologist at an advanced center
      for further care. His 2D echo revealed hypertrophic obstructive cardiomyopathy,
      all the other investigations were normal. His father was also found to have a
      similar condition however the father was asymptomatic. The patient underwent an
      automated implantable cardioverter-defibrillator implantation and was advised the
      necessary precautions and care. 

PMID- 25374876
TI  - Hospitalized Patients with Severe and Non-severe Pandemic Influenza A (H1N1).

PMID- 25374875
TI  - Diabetic Tongue - Could it be a Diagnostic Criterion?
AB  - Diabetes mellitus (DM) is a common disease which usually manifests in the form of
      polyuria, polydipsia, weight loss, fatigue, weakness, blurry vision, frequent
      skin infections, and slow healing of skin lesions. Taste disturbances like
      ageusia, hypogeusia and dysgeusia have been associated with DM. The early
      diagnosis of DM based on these symptoms is very important to start treatment
      early and thereby prevent complications. We present an interesting case of a
      female presenting with altered taste as the first symptom of DM. 

PMID- 25374877
TI  - Referral letter and reply form.

PMID- 25374878
TI  - Community-Based Rehabilitation is an Option to Address Challenges of Disabilities
      in India.

PMID- 25374879
TI  - Comment on: effect of pomegranate flower extract oncis platin-induced
      nephrotoxicity in rats.

PMID- 25374880
TI  - A honeycomb glomerular mesangial appearance on ultrastructural examination with
      minimal IgA deposition in a case of hepatic glomerulosclerosis: a case report.

PMID- 25374881
TI  - Prevalence of cryptosporidiosis in renal transplant recipients presenting with
      acute diarrhea at a single center in Pakistan.
AB  - BACKGROUND: Cryptosporidium is an intracellular protozoan organism which causes
      diarrhea, both in immunocompetent and immunocompromised hosts. Renal transplant
      recipients are prone to develop a variety of infections including protozoal
      infections. OBJECTIVES: The aim of this study was to determine the prevalence of
      cryptosporidiosis in our renal transplant recipients presenting with acute
      diarrhea. PATIENTS AND METHODS: During six months of the study, 644 renal
      transplant recipients presented with acute diarrhea. Single stool sample was
      obtained for detailed analysis including gross and microscopic examination for
      red blood cells, pus cells, ova, cysts, and protozoa. The modified Ziehl-Neelsen
      (ZN) staining was done to identify the oocysts of cryptosporidia. RESULTS: Out of
      644 renal transplant patients, oocysts of cryptosporidia were identified in 343
      patients (53%). Detailed stool analysis of these patients showed the presence of
      numerous pus cells in 27 (7.9%) patients, co-infection with giardia intestinalis
      cysts in 15 (4.3%), and entamoeba histolytica cysts in 10 (2.9%). In all, out of
      343 patients, 43 (12.5%) had dual infection with bacteria and protozoa in
      addition to cryptosporidiosis. CONCLUSIONS: Cryptosporidium is an important
      pathogen causing acute diarrhea in renal transplant recipients in our set up.
      Stool examination is usually negative for pus cells. It is recommended that in
      all transplant recipients presenting with acute diarrhea modified ZN staining
      should be done to rule out cryptosporidiosis in highly endemic areas like
      Pakistan.

PMID- 25374882
TI  - Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats.
AB  - BACKGROUND: Chemotherapy with cisplatin (CP) is accompanied with nephrotoxicity.
      OBJECTIVES: In the current study, pomegranate flower extract (PFE) has been
      evaluated as an antioxidant agent against CP-induced-renal toxicity. MATERIALS
      AND METHODS: Thirty two male Wistar rats were divided into five groups (6-8 in
      each group). The animals in groups 1 to 3 received PFE (25 mg/kg), PFE (50
      mg/kg), and placebo (saline), respectively for 9 days, and onset of the day 3,
      they also received CP (2.5 mg/kg/day). Groups 4 and 5 were treated with PFE (25
      and 50 mg/kg/day) for 9 days. Finally, the animals were sacrificed at day 9 after
      collecting blood samples. Kidneys were removed, weighted, and underwent
      histopathological investigation. RESULTS: The mean serum level of creatinine in
      group 3 (treated with CP and placebo) increased significantly (p<0.05), but the
      value decreased significantly (p<0.05) in group 1. Kidney weight in group 1 was
      lower than KW in groups 2 and 3, however it was significant when compared with
      group 2 (p<0.05). The serum nitrite level in group 2 was non-significantly lower
      than that in other groups, and no significant changes were observed in serum
      levels of malondialdehyde (MDA). Tissue level of nitrite was significantly
      decreased in the positive control and high dose of PFE plus CP-treated groups
      (p<0.05). Among CP-treated groups, low dose of PFE significantly improved kidney
      nitrite level (p<0.05). The results from histopathological staining indicated
      less tissue damage in group 1 when compared with group 3. CONCLUSIONS: It seems
      that low dose of PFE plays a protective role against CP-induced renal toxicity in
      rats.

PMID- 25374883
TI  - The impact of cytomegalovirus infection on new-onset diabetes mellitus after
      kidney transplantation: a review on current findings.
AB  - CONTEXT: New onset diabetes mellitus after transplantation (NODAT) increases the
      risk of cardiovascular disease, rate of infections, graft rejection and graft
      loss as well as decreases patient and graft survival rates. There is a
      controversy surrounding the impact of cytomegalovirus (CMV) infection in the
      development of NODAT. This meta-analysis aims to identify the role of CMV
      infection leading to the development of NODAT in kidney recipient patients.
      EVIDENCE ACQUISITIONS: We searched several electronic databases, including
      PubMed, Embase, Medline, Scopus, Trip Database and Google Scholar for studies
      that completely fulfill our criteria between January 1990 and January 2014
      RESULTS: Seven studies with 1389 kidney transplant patients were included in this
      metaanalysis.The mean age of patients ranged from 42.8 to 48.8 years and males
      made up 53% to 75% of patients in the cohort studies. The incidence of NODAT
      varies from 14.3% to 27.1% in these studies. Overall adj OR was 1.94 [exp (0.66)]
      with a 95% CI of 1.26-2.98 [exp (0.23) and (1.09)]. There was no significant
      publication bias based on the Begg's and Egger's test (p value = 0.17 and 0.54,
      respectively). CONCLUSIONS: Our study showed that CMV infection is a risk factor
      for increasing incidence of NODAT. Thus, prophylaxis against CMV infection after
      kidney transplantation is strongly suggested. However, further clinical trials
      and cohorts are needed to confirm this association.

PMID- 25374884
TI  - Acute early transplant renal artery thrombosis; a complex etiologic diagnosis.

PMID- 25374885
TI  - Assessment of Dietary Intake Patterns and Their Correlates among University
      Students in Lebanon.
AB  - INTRODUCTION: Unhealthy dietary habits are major risk factors for chronic
      diseases, particularly if adopted during early years of adulthood. Limited
      studies have explored the food consumption patterns among young adults in
      Lebanon. Our study aimed to examine common dietary patterns and their correlates
      among a large sample of university student population in Lebanon, focusing on
      correlation with gender and body mass index (BMI). METHODS: A cross-sectional
      study was carried out on 3384 students, using a proportionate cluster sample of
      Lebanese students from both public and private universities. A self-administered
      food frequency questionnaire was used to assess dietary intake of university
      students. Factor analysis of food items and groups, cluster analysis of dietary
      patterns, and multivariate regressions were carried out. RESULTS: Three dietary
      patterns were identified among university youth namely a vegetarian/low calorie
      dietary pattern (characterized mainly by consumption of plant-based food while
      avoiding "western" food, composite dishes, and bread); a mixed dietary pattern
      (characterized by high consumption of plant-based food, followed by composite
      dishes, bread, and a low consumption of western type food); and finally, a
      westernized dietary pattern (characterized by high consumption of white bread and
      western food, and a strong avoidance of plant food and composite dishes). We
      observed significant differences between males and females in terms of their
      reported food intake and dietary patterns. Females were particularly more prone
      to adopt the vegetarian/low calorie diet than males (ORa = 1.69; p < 0.001),
      while males were more likely to adopt a westernized diet (ORa = 1.51; p < 0.001),
      seemingly in private universities (p = 0.053). Students with high income and
      obese students (BMI >= 30 kg/m(2)) were more likely to consume vegetarian/low
      calorie diets (p < 0.05). CONCLUSION: Male university students reported a higher
      consumption of the westernized dietary pattern as compared to female university
      students in Lebanon, while the latter reported a higher adoption of a vegetarian
      diet. Health promotion programs are needed to address the dietary intakes and
      lifestyle behaviors of young adults in Lebanon to help prevent obesity and other
      associated comorbidities.

PMID- 25374886
TI  - Warming reduces tall fescue abundance but stimulates toxic alkaloid
      concentrations in transition zone pastures of the U.S.
AB  - Tall fescue pastures cover extensive acreage in the eastern half of the United
      States and contribute to important ecosystem services, including the provisioning
      of forage for grazing livestock. Yet little is known concerning how these
      pastures will respond to climate change. Tall fescue's ability to persist and
      provide forage under a warmer and wetter environment, as is predicted for much of
      this region as a result of climate change, will likely depend on a symbiotic
      relationship the plant can form with the fungal endophyte, Epichloe coenophiala.
      While this symbiosis can confer environmental stress tolerance to the plant, the
      endophyte also produces alkaloids toxic to insects (e.g., lolines) and mammals
      (ergots; which can cause "fescue toxicosis" in grazing animals). The negative
      animal health and economic consequences of fescue toxicosis make understanding
      the response of the tall fescue symbiosis to climate change critical for the
      region. We experimentally increased temperature (+3 degrees C) and growing season
      precipitation (+30% of the long-term mean) from 2009-2013 in a mixed species
      pasture, that included a tall fescue population that was 40% endophyte-infected.
      Warming reduced the relative abundance of tall fescue within the plant community,
      and additional precipitation did not ameliorate this effect. Warming did not
      alter the incidence of endophyte infection within the tall fescue population;
      however, warming significantly increased concentrations of ergot alkaloids (by 30
      40%) in fall-harvested endophyte-infected individuals. Warming alone did not
      affect loline alkaloid concentrations, but when combined with additional
      precipitation, levels increased in fall-harvested material. Although future
      warming may reduce the dominance of tall fescue in eastern U.S. pastures and have
      limited effect on the incidence of endophyte infection, persisting endophyte
      infected tall fescue will have higher concentrations of toxic alkaloids which may
      exacerbate fescue toxicosis. 

PMID- 25374887
TI  - In silico genome comparison and distribution analysis of simple sequences repeats
      in cassava.
AB  - We conducted a SSRs density analysis in different cassava genomic regions. The
      information obtained was useful to establish comparisons between cassava's SSRs
      genomic distribution and those of poplar, flax, and Jatropha. In general, cassava
      has a low SSR density (~50 SSRs/Mbp) and has a high proportion of
      pentanucleotides, (24,2 SSRs/Mbp). It was found that coding sequences have 15,5
      SSRs/Mbp, introns have 82,3 SSRs/Mbp, 5' UTRs have 196,1 SSRs/Mbp, and 3' UTRs
      have 50,5 SSRs/Mbp. Through motif analysis of cassava's genome SSRs, the most
      abundant motif was AT/AT while in intron sequences and UTRs regions it was AG/CT.
      In addition, in coding sequences the motif AAG/CTT was also found to occur most
      frequently; in fact, it is the third most used codon in cassava. Sequences
      containing SSRs were classified according to their functional annotation of Gene
      Ontology categories. The identified SSRs here may be a valuable addition for
      genetic mapping and future studies in phylogenetic analyses and genomic
      evolution. 

PMID- 25374888
TI  - H-CRRETAWAC-OH, a lead structure for the development of radiotracer targeting
      integrin alpha5beta1?
AB  - Imaging of angiogenic processes is of great interest in preclinical research as
      well as in clinical settings. The most commonly addressed target structure for
      imaging angiogenesis is the integrin alpha(v)beta(3). Here we describe the
      synthesis and evaluation of [(18)F]FProp-Cys(*)-Arg-Arg-Glu-Thr-Ala-Trp-Ala
      Cys(*)-OH, a radiolabelled peptide designed to selectively target the integrin
      alpha(5)beta(1). Conjugation of 4-nitrophenyl-(RS)-2-[(18)F]fluoropropionate
      provided [(18)F]FProp-Cys(*)-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys(*)-OH in high
      radiochemical purity (>95%) and a radiochemical yield of approx. 55%. In vitro
      evaluation showed alpha(5)beta(1) binding affinity in the nanomolar range,
      whereas affinity to alpha(v)beta(3) and alpha(IIb)beta(3) was >50 MUM. Cell
      uptake studies using human melanoma M21 (alpha(v)beta(3)-positive and
      alpha(5)beta(1)-negative), human melanoma M21-L (alpha(v)beta(3)-negative and
      alpha(5)beta(1)-negative), and human prostate carcinoma DU145 (alpha(v)beta(3)
      negative and alpha(5)beta(1)-positive) confirmed receptor-specific binding. The
      radiotracer was stable in human serum and showed low protein binding.
      Biodistribution studies showed tumour uptake ranging from 2.5 to 3.5% ID/g
      between 30 and 120 min post-injection. However, blocking studies and studies
      using mice bearing alpha(5)beta(1)-negative M21 tumours did not confirm receptor
      specific uptake of [(18)F]FProp-Cys(*)-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys(*)-OH,
      although this radiopeptide revealed high affinity and substantial selectivity to
      alpha(5)beta(1) in vitro. Further experiments are needed to study the in vivo
      metabolism of this peptide and to develop improved radiopeptide candidates
      suitable for PET imaging of alpha(5)beta(1) expression in vivo.

PMID- 25374889
TI  - The prognostic impact of high on-treatment platelet reactivity with aspirin or
      ADP receptor antagonists: systematic review and meta-analysis.
AB  - OBJECTIVE: Negative results of recent randomized clinical trials testing the
      hypothesis of target therapy for patients with high on-treatment platelet
      reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26
      studies with 28.178 patients were included, with a median age of 66.8 (64-68) and
      22.7% (22.4-27.8), of female gender. After a median follow-up of 1 year (0.1-1),
      cardiac adverse events occurred in 8.3% (3-11; all results are reported as median
      and interquartile range) of patients. Pooling all studies together, on-treatment
      platelet reactivity significantly increased the risk of adverse events (OR 1.33
      [1.09, 1.64], I(2) = 0%). However, a sensitivity analysis showed that HOPR did
      not increase the risk of adverse events for patients with ACS, AMI, or stable
      angina as well as patients resistant to aspirin, ADP antagonists, or both. For
      all studies, publication bias was formally evident; after adjusting for this,
      HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89-1.22,
      I(2) 0%). CONCLUSIONS: After adjusting for clinical confounders (like risk
      factors and clinical presentation) and for relevant publication bias, HOPR was
      not an independent prognostic indicator in unselected patients with both stable
      and unstable coronary disease for an adverse cardiac event. The clinical
      importance of HOPR for high-risk populations remains to be assessed.

PMID- 25374890
TI  - Heat shock protein 90 in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the first most common neurodegenerative disease.
      Despite a large amount of research, the pathogenetic mechanism of AD has not yet
      been clarified. The two hallmarks of the pathology of AD are the extracellular
      senile plaques (SPs) of aggregated amyloid-beta (Abeta) peptide and the
      accumulation of the intracellular microtubule-associated protein tau into
      fibrillar aggregates. Heat shock proteins (HSPs) play a key role in preventing
      protein misfolding and aggregation, and Hsp90 can be viewed as a ubiquitous
      molecular chaperone potentially involved in AD pathogenesis. A role of Hsp90
      regulates the activity of the transcription factor heat shock factor-1 (HSF-1),
      the master regulator of the heat shock response. In AD, Hsp90 inhibitors may
      redirect neuronal aggregate formation, and protect against protein toxicity by
      activation of HSF-1 and the subsequent induction of heat shock proteins, such as
      Hsp70. Therefore, we review here to further discuss the recent advances and
      challenges in targeting Hsp90 for AD therapy. 

PMID- 25374891
TI  - Clinical relevance of HLA antibody monitoring after kidney transplantation.
AB  - In kidney transplantation, antibody-mediated allograft injury caused by donor HLA
      specific antibodies (DSA) has recently been identified as one of the major causes
      of late graft loss. This paper gives a brief overview on the impact of DSA
      development on graft outcome in organ transplantation with a focus on risk
      factors for de novo alloantibody induction and recently published guidelines for
      monitoring of DSA during the posttransplant phase. 

PMID- 25374892
TI  - Mirtazapine in Comorbid Major Depression and Alcohol Use Disorder: A Long-Term
      Follow-Up Study.
AB  - BACKGROUND/OBJECTIVE: To date, pharmacotherapy trials of depressed alcoholics
      (MDD/AUD) have focused on SSRI medications, with disappointing results, so
      effective treatments for that comorbid population are lacking. Mirtazapine is an
      FDA-approved medication for treating MDD with a unique pharmacological profile
      whose efficacy may exceed that of SSRIs. Results from our recent open label study
      suggest robust acute phase efficacy for mirtazapine for decreasing both the
      depression and the drinking of that population. However, to date, no studies have
      evaluated the longer-term efficacy of mirtazapine in that population. We now
      report findings from a first long-term (two-year) naturalistic follow-up
      evaluation involving subjects from the acute phase trial. We hypothesized that
      the improvements would persist at follow-up. METHODS: An eight-week open label
      study of mirtazapine and motivation therapy was conducted involving persons 18 to
      55 years of age with DSM-IV diagnoses of comorbid MDD/AD. Two years after entry
      into the acute phase study, a long-term evaluation was conducted using the same
      instruments that had been used at baseline to assess whether the improvements
      seen during the acute phase trial had persisted. RESULTS: Ten of the twelve
      patients who entered the acute phase study participated in the follow-up study.
      The large magnitude improvements (p<.01) in depressive symptoms (BDI), drinking
      (TLFB), and sleep disturbance (HDRS) persisted at the follow-up evaluation. Two
      of the subjects demonstrated MDD on structured interview at follow-up, while all
      ten had demonstrated MDD at baseline. Six of the ten used antidepressants during
      the follow-up period. At baseline, three were employed, while at follow-up seven
      were employed. CONCLUSIONS: These findings suggest long-term efficacy for
      mirtazapine for decreasing the drinking and depression of depressed alcoholics.
      Double-blind, placebo-controlled studies are warranted to clarify the efficacy of
      mirtazapine in depressed alcoholics.

PMID- 25374894
TI  - Launching of american journal of clinical and experimental urology.

PMID- 25374893
TI  - Aberrations in Angiogenic Signaling and MYC Amplifications are Distinguishing
      Features of Angiosarcoma.
AB  - Angiosarcomas are very aggressive, rare malignant tumors that originate from
      vascular or lymphatic vessels and primarily occur following chemical exposure or
      radiation therapy. Tumor response to either chemotherapy, radiation, or novel
      anti-angiogenic therapeutics is very low, and because little is known regarding
      the aberrant signaling that controls these tumors, personalized treatment options
      for many of these patients are lacking. In this review, we summarize several
      recent findings regarding the genomics of angiosarcomas, including new
      discoveries regarding aberrant angiogenic signaling and Myc amplification as key
      features of this tumor type.

PMID- 25374895
TI  - Multidisciplinary management of Prostate Cancer: how and why.
AB  - BACKGROUND: A Prostate Cancer Unit is a place where men can be cared for by
      specialists in prostate cancer (PC), working together within a multi-disciplinary
      team (MDT). The MDT approach guarantees a higher probability for the PC patient
      to receive adequate information on the disease and on all possible therapeutic
      strategies, balancing advantages and related side effects. Objecive: To analyze
      the role of a MDT in PC management and to compare some results in terms of
      characteristics and distribution of PC cases, obtained by a MDT, with those
      reported by a monodisciplinary urological unit. Outcome measurements and results:
      A high percentage of cases (47.6%) referred to our MDT were in the low risk
      group. In the Prostate cancer Unit the indications for primary therapies were
      more equally distributed between surgery (51.5%) and radiotherapy (45.4%).
      CONCLUSIONS: The future of PC patients relies in a successful multidisciplinary
      collaboration between experienced physicians which can led to important
      advantages in all the phases of PC.

PMID- 25374896
TI  - Splicing variants of androgen receptor in prostate cancer.
AB  - Significant advances in our understanding of continued androgen receptor (AR)
      signaling in castration-resistant prostate cancer have led to the development and
      FDA approval of two next-generation androgen-directed therapies, abiraterone and
      enzalutamide. These new therapies heralded a new era of prostate cancer therapy.
      However, disease progression during androgen-directed therapies remains the most
      critical challenge in the clinical management of prostate cancer. Accumulating
      evidence points to an important contribution of constitutively-active AR splice
      variants to AR-driven tumor progression during androgen-directed therapies. In
      this review, we will focus on the structure, activity, detection, clinical
      relevance, and mechanisms of production of AR splice variants. 

PMID- 25374897
TI  - Mini-review: androgen receptor phosphorylation in prostate cancer.
AB  - Androgen receptor (AR) plays an important role in the tumorigenesis and
      progression of prostate cancer (PCa), and is the primary therapeutic target for
      PCa treatment. AR activity can be regulated via phosphorylation at multiple
      phosphorylation sites within the protein. Modifications by phosphorylation alter
      AR function, including its cellular localization, stability and transcriptional
      activity, ultimately leading to changes in cancer cell biology and disease
      progression. Here we present a brief overview of AR phosphorylation sites in PCa,
      focusing on functional roles of phospho-AR (p-AR) species, relevance in PCa
      disease progression, and potential as biomarkers and/or therapeutic targets
      through the use of kinase inhibitors. Additionally, recent evidence has shown the
      important role of AR activity in the cancer associated stroma on PCa growth and
      progression. The phosphorylation status of epithelial and stromal AR may be
      distinct; however, the current data available on stromal AR phosphorylation is
      limited. Further research will determine global view on the synergistic effects
      of phosphorylation across multiple AR sites in both epithelial and stromal cells
      and validate whether together they can be used as prognostic markers and/or
      effective therapeutic targets for PCa. 

PMID- 25374898
TI  - Current treatments and novel therapeutic targets for castration resistant
      prostate cancer with bone metastasis.
AB  - Prostate cancer is a leading cause of cancer death in men in developed countries.
      While early stage disease can often be cured, many patients eventually develop
      castration resistant prostate cancer (CRPC). The majority of CRPC patients have
      bone metastases, which cause significant morbidity and mortality. Although there
      is no cure for prostate cancer metastatic to bone, several bone-targeted agents
      have been approved to prevent skeletal-related events (SREs). Among them,
      bisphosphonates were the first class of drugs investigated for prevention of
      SREs. Denosumab is a recently approved agent that binds to the receptor activator
      of nuclear factor-kappaB ligand (RANKL) as a humanized monoclonal antibody. Both
      agents target prostate cancer skeletal metastasis through the inhibition of bone
      resorption. Alpharadin is the first radiopharmaceutical agent that has
      significant overall survival benefit. It has benefits in pain palliation and SREs
      as well. Another newly approved drug is Abiraterone acetate, which decreases
      circulating levels of testosterone by targeting an enzyme expressed in the testis
      and the adrenal, as well as in prostate cancer tissues. This review outlines the
      clinical and preclinical data supporting the use of these and new agents in
      development for CRPC with bone metastasis. 

PMID- 25374899
TI  - Prostate-associated gene 4 (PAGE4) protects cells against stress by elevating p21
      and suppressing reactive oxygen species production.
AB  - BACKGROUND: It is now widely recognized that there is a strong correlation
      between oxidative stress and the risk of benign and malignant diseases of the
      prostate. Prostate-associated gene 4 (PAGE4) is a Cancer/Testis Antigen (CTA)
      that was previously shown to be up-regulated in prostate cancer (PCa) and
      symptomatic as opposed to histologic benign prostatic hyperplasia (BPH). However,
      its functional role in these diseases is not fully understood. METHODS: The mRNA
      level of PAGE4 was detected in isolated cell types in PCa tissues that were
      obtained from 8 men with PCa. PAGE4 protein expression profile was analyzed in a
      prostate disease tissue microarray. PAGE4 was overexpressed by pCMV-PAGE4-GFP
      transfection and cell viability was determined using the WST-1 assay. RESULTS:
      PAGE4 expression is highly dynamic; while its expression is very high in fetal
      prostate it is drastically decreased in the normal adult prostate but is up
      regulated both in symptomatic BPH and PCa. However, in the diseased prostate,
      PAGE4 is highly expressed in the epithelial cells of Proliferative Inflammatory
      Atrophy (PIA) lesions alluding to a potential stress response function of PAGE4.
      Consistent with such a role, PAGE4 protein levels are up-regulated when prostate
      cancer (PCa) cell lines are treated with various stress factors including the
      proinflammatory cytokine TNFalpha. Interestingly, in cells challenged with stress
      there is increased translocation of the PAGE4 protein to the mitochondrion and
      production of reactive oxygen species is suppressed . Furthermore, p21 is
      elevated in a p53-independent manner in PAGE4-overexpressing cells which results
      in impeded cell cycle progression, attenuated stress-induced DNA damage, and
      decreased cell death. CONCLUSIONS: PAGE4 may be contributing to the development
      of PCa by playing a stress-protective and anti-apoptotic role.

PMID- 25374900
TI  - Anti-androgen resistance in prostate cancer cells chronically induced by
      interleukin-1beta.
AB  - Chronic inflammation has been linked to cancer initiation and progression in a
      variety of tissues, yet the impact of acute and chronic inflammatory signaling on
      androgen receptor function has not been widely studied. In this report, we
      examine the impact of the inflammation-linked cytokine, interleukin-1beta on
      androgen receptor function in prostate cancer cells. We demonstrate that acute
      interleukin-1beta treatment inhibits the transcription of the androgen receptor
      gene itself, resulting in the reduction of androgen receptor protein levels.
      Interestingly, in cells subjected to chronic interleukin-1beta stimulation, the
      transcription of the androgen receptor gene is restored within a few cell
      passages and the cells acquire the ability to grow in the presence of the anti
      androgen, bicalutamide. Importantly, the changes that accompany this loss of
      androgen receptor regulation and gain of anti-androgen resistance are stably
      heritable since once established, the phenotype is maintained even in the absence
      of exogenously added interleukin-1beta. Further, bicalutamide resistance
      correlates with increased transcription of androgen receptor target genes and
      histone H3K4 dimethylation at M-phase gene enhancers. Overall, our studies
      demonstrate a novel route to anti-androgen resistance upon exposure to an
      inflammatory cytokine and provide a new tool to further understand how anti
      androgen resistance emerges under chronic inflammation. 

PMID- 25374901
TI  - Complications of initial prostate biopsy in a European randomized screening
      trial.
AB  - BACKGROUND: Transrectal prostate needle biopsy (PNB) is a standard procedure for
      the diagnosis of prostate cancer. We recently found an increasing frequency of
      hospitalization with infectious complications associated with PNB over time.
      OBJECTIVE: To perform an updated analysis of overall complication rates in a
      large screening population over the past 18 years and to examine possible
      predictors of complications on initial PNB. DESIGN, SETTING AND PARTICIPANTS:
      From 1993-2011, 7216 men underwent initial lateralized sextant PNB in European
      Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam. After 2
      weeks a questionnaire was administered to 6962 men regarding PNB-related
      complications. Outcome Measurements & Statistical Analysis: Overall complication
      rates as well as specific complications (hematuria for >3 days, hematospermia,
      significant pain after biopsy, fever, and hospitalizations) were prospectively
      recorded. Multivariable logistic regression models were performed to assess the
      relationship between age, comorbidities, and prostate volume with specific
      complications. RESULTS AND LIMITATIONS: A total of 4674 (67.1%) men reported any
      sequelae after initial PNB, with hematospermia as the most frequent (53.8%),
      followed by hematuria (24.3%). Significant pain (4.8%), fever (4.1%), and
      hospital admission (0.7%) were reported less frequently. Hematospermia was
      significantly more likely in younger men with fewer comorbidities and smaller
      prostate volume; whereas hematuria was significantly more frequent among men with
      increasing comorbidities and prostate volume. In addition, pain was inversely
      associated with age and was also reported less frequently during later years of
      biopsy. Limitations of our study include the use of sextant biopsies and a
      relatively healthy population, while strengths include the large sample size and
      data on patient-specific covariates. CONCLUSION: Many men experience minor
      complications after initial PNB, although the frequency of specific complications
      such as hematospermia and hematuria differed based upon factors such as prostate
      volume and comorbidities. Overall, these data are useful to counsel patients who
      are undergoing their first PNB on the frequency of complications in a screening
      population.

PMID- 25374902
TI  - Active surveillance in men with low-risk prostate cancer: current and future
      challenges.
AB  - INTRODUCTION: The implementation of prostate-specific antigen (PSA) screening has
      coincided with a decrease in mortality rate from prostate cancer at the cost of
      overtreatment. Active surveillance has thus emerged to address the concern for
      over-treatment in men with low-risk prostate cancer. METHODS: A contemporary
      review of literature with respect to low-risk prostate cancer and active
      surveillance was conducted. The premise of active surveillance, ideal candidates,
      follow-up practices, treatment triggers, and the observed outcomes of delayed
      interventions are reviewed. Various institutional protocols are compared and
      contrasted. RESULTS: Eligibility criteria from various institutions share similar
      principles. Candidates are followed with PSA kinetics and/or repeat biopsies to
      identify those who require intervention. Various triggers for intervention have
      been recognized achieving overall and cancer-specific survival rates > 90% in
      most protocols. New biomarkers, imaging modalities and genetic tests are also
      currently being investigated to enhance the efficacy of active surveillance
      programs. CONCLUSION: Active surveillance has been shown to be safe and effective
      in managing men with low-risk prostate cancer. Although as high as 30% of men on
      surveillance will eventually need intervention, survival rates with delayed
      intervention remain reassuring. Long-term studies are needed for further
      validation of current active surveillance protocols.

PMID- 25374904
TI  - Biomarkers for bladder cancer management: present and future.
AB  - Accurate and sensitive detection of bladder cancer is critical to diagnose this
      deadly disease at an early stage, estimate prognosis, predict response to
      treatment, and monitor recurrence. In past years, laboratory diagnosis and
      surveillance of urinary bladder cancer have improved significantly. Although
      urine cytology remains the gold standard test, many new urinary biomarkers have
      been identified. Furthermore, recent advances in genomic studies of bladder
      cancer have helped to refine our understanding of the pathogenesis of the
      disease, the biological basis for outcome disparities, and to inform more
      efficient treatment and surveillance strategies. In this article, the established
      diagnostic tests, newly identified biomarkers and genomic landscape of bladder
      cancer will be reviewed. 

PMID- 25374905
TI  - Cytoskeleton targeting value in prostate cancer treatment.
AB  - Prostate cancer is a disease that affects hundreds of thousands of men in the
      United States each year. In the early stages of advanced prostate cancer, the
      disease can be suppressed by androgen deprivation therapy (ADT). Eventually,
      however, most patients experience resistance to androgen deprivation, and their
      treatment transitions to alternative targeting of the androgen axis with
      abiraterone and enzalutamide, as well as taxane-based chemotherapy. Development
      of advanced castration-resistant prostate cancer (CRPC) is a consequence of lack
      of an apoptotic response by the tumor cells to treatment. Understanding the
      mechanisms contributing to prostate tumor therapeutic resistance and progression
      to metastasis requires dissection of the signaling mechanisms navigating tumor
      invasion and metastasis as mediated by cell-matrix interactions engaging
      components of the extracellular matrix (ECM), to form adhesion complexes. For a
      tumor call to metastasize from the primary tumor, it requires disruption of cell
      cell interactions from the surrounding cells, as well as detachment from the ECM
      and resistance to anoikis (apoptosis upon cell detachment from ECM). Attachment,
      movement and invasion of cancer cells are functionally facilitated by the actin
      cytoskeleton and tubulin as the structural component of microtubules.
      Transforming growth factor (TGF)-beta has tumor-inhibitory activity in the early
      stages of tumorigenesis, but it promotes tumor invasive characteristics in
      metastatic disease. Recent evidence implicates active (dephosphorylated) cofilin,
      an F-actin severing protein required for cytoskeleton reorganization, as an
      important contributor to switching TGF-beta characteristics from a growth
      suppressor to a promoter of prostate cancer invasion and metastasis. Cancer cells
      eventually lose the ability to adhere to adjacent neighboring cells as well as
      ECM proteins, and via epithelial-mesenchymal transition (EMT), acquire invasive
      and metastatic characteristics. Microtubule-targeting chemotherapeutic agents,
      taxanes, are used in combination with antiandrogen strategies to increase the
      survival rate in patients with CRPC. This review addresses the development of
      therapeutic platform for targeting the integrity of actin cytoskeleton to impair
      prostate cancer progression. 

PMID- 25374907
TI  - Primary localized amyloidosis of the urinary tract frequently mimics neoplasia: a
      clinicopathologic analysis of 11 cases.
AB  - Localized urinary tract amyloidosis (UTA) is a rare disease that mimics neoplasia
      clinically, cystoscopically, and radiologically. We report eleven cases of
      isolated UTA from the urinary bladder (n=7) and upper urinary tract including the
      ureter (n=2) and renal pelvis (n=2). All cases clinically presented as mass
      lesions prior to histologic examination and clinically suggested a neoplastic
      process. The amyloid composition in most cases was mixed Kappa and Lambda light
      chains. All cases were cured after surgical excision except one case which was
      diagnosed as plasmacytosis/plasmacytoma six months later. Localized amyloidosis
      of the urinary tract usually has a benign clinical course and simple resection is
      recommended after systemic disease is ruled out. 

PMID- 25374906
TI  - Androgen receptor coactivators that inhibit prostate cancer growth.
AB  - It is well documented that androgen receptor (AR), a steroid hormone receptor, is
      important for prostate cancer (PCa) growth. Conversely, however, there is
      increasing evidence that activation of AR by androgens can also lead to growth
      suppression in prostate cells. AR mediated transcription is regulated by a number
      of different transcriptional coactivators. Changes in expression level or
      cellular localization of specific coactivators may play a crucial role in this
      switch between proliferative and anti- proliferative processes regulated by AR
      target gene programs. In this review, we discuss the expression and function of
      several AR coactivators exhibiting growth suppressive function in PCa, including
      ARA70/ELE1/NCOA4, androgen receptor coactivator p44/MEP50/WDR77, TBLR1, and ART
      27. In luciferase reporter assays, they all have been shown to activate AR
      mediated transcriptional activation. ARA70 exists in two forms, the full length
      nuclear ARA70alpha and internally spliced cytoplasmic ARA70beta. For p44 and
      TBLR1, we identified nuclear and cytoplasmic forms with distinct expression and
      function. In comparison of their expression (ARA70alpha, p44, TBLR1 and ART-27)
      in prostate, these coactivators are expressed in the nucleus of benign prostate
      epithelial cells while they are more predominantly expressed in cytoplasmic form
      (ARA70beta, cytoplasmic p44 and TBLR1) in PCa. Consistent with their nuclear
      expression in benign prostate, the nuclear form of these coactivators inhibit PCa
      growth targeting a subset of AR target genes. In contrast, the cytoplasmic
      versions of these proteins enhance PCa growth and invasion. Interestingly, first
      characterized as an AR coactivator in luciferase assays, ART-27 functions as
      corepressor for endogenous AR target genes. Importantly, the growth inhibitions
      by these nuclear proteins are androgen-dependent processes and the regulation of
      invasion is androgen-independent. Understanding the molecular switches involved
      in the transition from AR dependent growth promotion to growth suppression and
      dysregulation of these coactivator proteins promoting androgen-independent
      invasion may lead to identification of novel therapeutic targets for PCa. 

PMID- 25374908
TI  - Glomerular sparing pattern in primary kidney neoplasms: clinical, morphological
      and immunohistochemical study.
AB  - Glomerular sparing (GS) is defined as a unique growth pattern in which tumor
      cells replace the majority of renal tubes and overrun intact glomeruli. This
      phenomenon has been well recognized by pathologists as a typical infiltrative
      pattern and some studies suggested it was an independent risk factor. Here, we
      study the clinical, pathological, and immunohistochemical features of primary
      kidney neoplasms with glomerular sparing pattern. We searched the archives of our
      pathology department for nephrectomy specimens and reviewed all pathology reports
      from 2009-2013. We selected cases with tumor and collected clinicopathological
      information, focusing on re-evaluation of cases with glomerular sparing pattern.
      To facilitate our study we performed immunohistochemical stains of PAX-8, p63,
      and InI-1 on selected cases. We selected a total of 204 nephrectomy cases in this
      study, including 163 cases of renal cell carcinoma; 37 cases of urothelial
      carcinoma; 4 cases from other categories (Wilms tumor, primary diffuse large B
      cell lymphoma, angiolipoma, rhabdoid tumor). Finally, we identified 7 cases of
      primary kidney tumors with glomerular sparing pattern: 2 cases of clear cell
      renal cell carcinomas (ccRCC), 1 case of collecting duct carcinoma, 2 cases of
      urothelial carcinoma (UC), 1 case of diffuse large B-cell lymphoma and 1 case of
      malignant rhabdoid tumor. The primary kidney tumors with glomerular sparing
      pattern are rare and incidence in our study is <4% (7/204). There is no
      specificity for any tumor type, but more commonly seen in high grade UC rather
      than RCC. It can also be seen in rare neoplasms such as collecting duct
      carcinoma, lymphoma and malignant rhabdoid tumor. These GS cases need to be
      recognized as they are often associated with high grade, high stage, large tumor
      size, and worse prognosis. 

PMID- 25374909
TI  - Growth of LAPC4 prostate cancer xenograft tumor is insensitive to 5alpha
      reductase inhibitor dutasteride.
AB  - Intermittent androgen deprivation therapy (IADT) allows prostate cancer patients
      a break from the side-effects of continuous androgen deprivation therapy (ADT).
      Although clinical studies suggest that IADT can significantly improve patient
      quality of life over ADT, it has not been demonstrated to improve patient
      survival. Recently, increased survival has been demonstrated when 5alpha
      reductase inhibitors have been used during the off-cycle of IADT in animal
      xenograft tumor models LNCaP and LuCaP35. In the current study, the sensitivity
      of LAPC4 xenograft tumor regrowth to the 5ARI dutasteride was determined. Tumor
      regrowth and gene expression changes in LAPC4 tumors were compared to the
      previously determined response of LNCaP and LuCaP35 xenograft tumors to 5ARI
      treatment during the off-cycle of IADT, LAPC4, LNCaP and LuCaP35 tumors were
      sensitive to androgen manipulation. However, in contrast to LNCaP and LuCaP35,
      dutasteride treatment during testosterone-stimulated prostate regrowth did not
      affect tumor regrowth or the expression of androgen responsive genes. Tumor
      response to dutasteride during the off-cycle of IADT is variable in xenograft
      prostate tumor models. Future studies will be required to elucidate the
      mechanisms contributing to the dutasteride resistance observed in the LAPC4 model
      during the off-cycle. 

PMID- 25374910
TI  - Prostate cancer progression and metastasis: potential regulatory pathways for
      therapeutic targeting.
AB  - Skeletal metastasis in advanced prostate cancer (PCa) patients remains a
      significant cause of morbidity and mortality. Research utilizing animal models
      during the past decade has reached a consensus that PCa progression and distant
      metastasis can be tackled at the molecular level. Although there are a good
      number of models that have shown to facilitate the study of PCa initiation and
      progression at the primary site, models that mimic the distant dissemination of
      cancer cells, particularly bone metastasis, are scarce. Despite this limitation,
      the field has gleaned valuable knowledge on the underlying molecular mechanisms
      and pathways of PCa progression, including local invasion and distant metastasis,
      and has moved forward in developing the concepts of current therapeutic
      modalities. The purpose of this review is to put together recent work on pathways
      that are currently being targeted for therapy, as well as other prospective novel
      therapeutic targets to be developed in the future against metastatic and
      potentially lethal PCa in patients. 

PMID- 25374911
TI  - Upper urinary tract urothelial carcinoma with intratubular spread.
AB  - Upper urinary tract urothelial cell carcinomas (UUT-UCs) are uncommon and are
      defined as urothelial carcinoma involving the urinary tract from the renal
      calyces, renal pelvis to the distal ureter. One well-known an peculiar
      histopathological finding in UUT-UC is urothelial carcinoma with intratubular
      spread (retrograde spread within renal tubules). However, this special feature
      has not been systematically studied. We therefore collected a total of 53
      consecutive cases of upper urinary tract urothelial carcinomas (UUT-UCs), and
      studied the clinical and pathological features of intratubular spread (IS). A
      cocktail stain comprised of antibodies PAX8 and p63 together with PAS was
      validated and employed to facilitate the study of intratubular spread. Seventeen
      cases (31.5%) showed intratubular spread demonstrated by either H&E stain and/or
      the cocktail stain. All of the 17 cases wit intratubular spread had tumor
      involvement of the renal calyx; the majority of these (14/17, 82.4%) were high
      grade urothelial carcinoma and the remainder (3/17, 17.6%) were low grade. 4 of
      17cases (23.5%) were non-invasive. We classified intratubular spread into 4
      different types, based on histopathological patterns: pagetoid, typical, florid,
      and secondary invasion from intratubular spread. In conclusion, study shows
      intratubular spread of urothelial carcinoma is fairly common phenomenon in UUT-UC
      and is associated with a variety of clinical-pathological features. High grade
      UUT-UC tends to have more extensive intratubular spread and secondary invasion
      into renal parenchyma. Distinct morphological characteristics as well as the
      staining pattern from a unique cocktail stain help to identify and evaluate
      intratubular spread of urothelial carcinoma. Recognizing these different types of
      intratubular spreading (IS) is crucial for accurate staging of some upper urinary
      tract urothelial carcinomas (UUT-UCs). 

PMID- 25374912
TI  - Lipid metabolism in prostate cancer.
AB  - The malignant transformation of cells requires adaptations across multiple
      metabolic processes to satisfy the energy required for their increased rate of
      proliferation. Dysregulation of lipid metabolism has been a hallmark of the
      malignant phenotype; increased lipid accumulation secondary to changes in the
      levels of a variety of lipid metabolic enzymes has been documented in a variety
      of tumors, including prostate. Alterations in prostate lipid metabolism include
      upregulation of several lipogenic enzymes as well as of enzymes that function to
      oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid
      metabolism are also affected. With respect to lipogenesis, most studies have
      concentrated on increased expression and activity ofthe de novo fatty acid
      synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might
      function as an oncogene. A central role for fatty acid oxidation in supplying
      energy to the prostate cancer cell is supported by the observation that the
      peroxisomal enzyme, alpha-methylacyl-CoA racemase (AMACR), which facilitates the
      transformation of branched chain fatty acids to a form suitable for beta
      oxidation, is highly overexpressed in prostate cancer compared with normal
      prostate. Exploitation of the alterations in lipid metabolic pathways in prostate
      cancer could result in the development of new therapeutic modalities as well as
      provide candidates for new prognostic and predictive biomarkers. AMACR has
      already proven to be a valuable biomarker in distinguishing normal from malignant
      prostate tissue, and is used routinely in clinical practice. 

PMID- 25374913
TI  - Revisiting nomenclature for the description of prostate cancer androgen
      responsiveness.
AB  - Ever since the Noble prize-winning findings of Huggins and Hodges, the androgen
      receptor (AR) has been the main target for treatment of advanced prostate cancer
      (CaP). Today, second- and even third-line androgen deprivation strategies, which
      have been designed rationally to interfere with the AR signaling that re-emerges
      under conditions of androgen deprivation and is at least in part responsible for
      disease recurrence, are effective in impeding progression of advanced CaP. The
      therapeutic success of these novel agents in CaP that has failed initial androgen
      deprivation therapy (ADT) and subsequent chemotherapy is prompting studies to
      explore their use earlier in the course of CaP progression. Repositioning of
      these drugs, along with alterations in the timing, sequencing and/or combination
      of traditional or novel ADTs, either alone or in combination with radiation or
      chemo- or immuno-therapies are expected to broaden significantly the scope of
      treatment options for CaP. Despite the rapidly changing and continuously
      innovating landscape of CaP therapies that target AR activity, the terminology
      that is used to describe CaP androgen status has not evolved. Currently available
      nomenclature falls short in capturing the sustained androgen-responsiveness of
      mostCaPs after ADT, does not distinguish readily between CaP's responsiveness to
      androgens and other steroid hormones, and does not specify the treatment
      condition(s) under which CaP recurs. A novel vocabulary is introduced to solve
      these limitations and to facilitate optimal communication among physicians,
      scientists and CaP patients. 

PMID- 25374914
TI  - A system for evaluating magnetic resonance imaging of prostate cancer using
      patient-specific 3D printed molds.
AB  - We have developed a system for evaluating magnetic resonance imaging of prostate
      cancer, using patient-specific 3D printed molds to facilitate MR-histology
      correlation. Prior to radical prostatectomy a patient receives a multiparametric
      MRI, which an expert genitourinary radiologist uses to identify and contour
      regions suspicious for disease. The same MR series is used to generate a prostate
      contour, which is the basis for design of a patient-specific mold. The 3D printed
      mold contains a series of evenly spaced parallel slits, each of which corresponds
      to a known MRI slice. After surgery, the patient's specimen is enclosed within
      the mold, and all whole-mount levels are obtained simultaneously through use of a
      multi-bladed slicing device. The levels are then formalin fixed, processed, and
      delivered to an expert pathologist, who identifies and grades all lesions within
      the slides. Finally, the lesion contours are loaded into custom software, which
      elastically warps them to fit the MR prostate contour. The suspicious regions on
      MR can then be directly compared to lesions on histology. Furthermore, the false
      negative and false-positive regions on MR can be retrospectively examined, with
      the ultimate goal of developing methods for improving the predictive accuracy of
      MRI. This work presents the details of our analysis method, following a patient
      from diagnosis through the MR-histology correlation process. For this patient MRI
      successfully predicted the presence of cancer, but true lesion volume and extent
      were underestimated. Most cancer-positive regions missed on MR were observed to
      have patterns of low T2 signal, suggesting that there is potential to improve
      sensitivity. 

PMID- 25374915
TI  - Potent increased risk of the initiation of DNA replication in human prostate
      cancer with the use of 5alpha-reductase inhibitors.
AB  - Recent clinical studies have raised the clinically important question of the
      relationship between dihydrotestosterone (DHT) and prostate cancer (PCa)
      progression. The significance of DHT or 5alpha-reductase inhibitors (5ARI) in PCa
      development and progression has not yet been fully characterized. The aim of this
      study was to determine whether the initiation of DNA replication was influenced
      by DHT in PCa. Three cell lines were used. LNCaP: a human PCa cell line that
      exhibits androgen-dependent proliferation, C4-2: a human PCa cell line that
      exhibits androgen-independent proliferation, and C4-2AT6: a castration resistant
      prostate cancer cell line. Two 5ARIs, finasteride and dutasteride, were used. We
      examined the mRNA expression of the components of pre-replication complex (Pre
      RC), CDC6, CDT1, and MCM2-7. DHT induced cell proliferation of LNCaP accompanied
      by significantly increased CDC6, CDT1, and MCM2-7 expression. In contrast to
      LNCaP, DHT inhibited cell proliferation in C4-2AT6 cells accompanied by decreased
      expression of CDC6, CDT1, and MCM2-7. These reverse effects resemble the effects
      of 5ARIs in Pre-RC. Treatment with finasteride or dutasteride inhibited CDC6
      expression in LNCaP, but both 5ARIs induced CDC6 expression in C4-2 and C4-2AT6
      cells.These results indicate that DHT showed reversal effects on PCa cell
      proliferation among prostate cancer cells based on androgen-dependence,
      accompanied by regulation of the initiation of DNA replication. 5ARIs may
      modulate the DNA replication system in someaggressive PCa through up-regulation
      of CDC6 expression. 

PMID- 25374916
TI  - Intravesical instillation of pentosan polysulfate encapsulated in a liposome
      nanocarrier for interstitial cystitis.
AB  - We determined the effect of intravesical instillation of pentosan polysulfate
      encapsulated in liposomes for refractory interstitial cystitis patients. This was
      an open label uncontrolled study. Subjects were recruited from a private urology
      practice. Inclusion criteria included patients who met NIDDK criteria for
      Interstitial Cystitis (IC) and who were responding poorly to conventional
      treatments. Exclusion criteria included evidence of a urinary tract infection,
      bladder cancer, or other forms of chronic cystitis. Patients received 400 mg of
      Pentosan Polysulfate (PP) encapsulated into liposomes as an intravesical
      instillation performed every 2 weeks for 3 months. Baseline and post treatment
      outcome measures were obtained that included the O'Leary-Sant Interstitial
      Cystitis Symptom and Problem Questionnaire and the Pelvic Pain and
      Urgency/Frequency Patient symptom Scale tests. A total of 37 instillations were
      used and no adverse events occurred. Clinically significant decreases in symptom
      scores greater than 50% were seen in virtually all outcome measures at 3 month
      follow up. All subjects reported remarkable subjective improvement in pain
      symptoms marked by decreased use of narcotics and increased enjoyment of daily
      activities. No patients developed systemic symptoms or poor tolerance of the
      instillations. Intravesical Pentosan Polysulfate encapsulated into liposomes can
      significantly decrease frequency, urgency, pain and improve quality of life for
      two months after deployment. Additional studies are needed to determine cellular
      effects of glycosaminoglycan restoration, ideal doses, dosing intervals, safety
      and cost-effectiveness of this therapy. 

PMID- 25374917
TI  - Vicious cycle of TGF-beta signaling in tumor progression and metastasis.
AB  - TGF-beta is an important biological mediator. It regulates a wide range of
      functions including embryonic development, wound healing, organ development,
      immuno-modulation, and cancer progression. Interestingly, TGF-beta is known to
      inhibit cell growth in benign cells but promote progression in cancer cells, a
      phenomenon known as TGF-beta paradox. TGF-beta stimulation in cancer cells leads
      to a differential Erk activation, which srves as the basis of TGF-beta paradox
      between benign and cancer cells. The critical events of TGF-beta mediated Erk
      activation are suppressed TBRs and elevated TGF-beta in tumor cells but not in
      benign cells. These events form the basis of the "vicious cycle of TGF-beta
      signaling". The term "vicious cycle", implies that, with each advancing cycle of
      TGF-beta signaling, the tumor will accumulate more TGF-beta and will be more
      "aggressive" than that of the previous cycle. Understanding this vicious cycle of
      TGF-beta signaling in tumor progression and metastasis will help us to predict
      indolent from aggressive cancers and will help us to develop novel anti-cancer
      strategies. 

PMID- 25374918
TI  - Intraoperative frozen section evaluation of ureteral and urethral margins:
      studies of 203 consecutive radical cystoprostatectomy for men with bladder
      urothelial carcinoma.
AB  - Intraoperative frozen section (FS) evaluation of ureteral and urethral margins is
      frequently requested during radical cystoprostatectomy in patients with bladder
      urothelial carcinoma. However, it is still controversial whether intraoperative
      FSs of ureteral and urethral margins are necessary in all patients with
      cystoprostatectomy or a risk-based assessment with limited to the high risk
      patients is the best approach. A total of 203 radical cystoprostatectomy
      specimens with FS evaluation on margin status from men treated for bladder
      urothelial carcinoma from 2003 to 2010 in our institution were reviewed.
      Clinicopathologic features studied include: patients' age, pathologic tumor
      stage, presence of carcinoma in- situ (CIS), and intraoperative FS diagnosis. All
      203 patients had intraoperative FS evaluation of ureter, and of these, 37
      patients had additional urethra FS evaluation. Of the 203 ureteral FS cases, 17
      (8.4%) had positive margin for CIS (16 cases) or CIS with invasive urothelial
      carcinoma (1 case). All 17 patients with positive ureteral margin on FS had
      concomitant CIS in the bladder (15.5%; 17 of 110 patients). In contrast, none of
      the patients without concomitant CIS (n=93) had positive ureteral margins on FS.
      Among 37 patients who also had FS evaluation on urethral resection margin, 3
      patients (8.1%) had positive margins for CIS and all three of them had
      concomitant CIS in the bladder. Positive ureteral/urethral margin was not
      associated with patients' age or tumor stage, but was significantly associated
      with the presence of CIS in the bladder (p<0.001). Our study demonstrates that
      presence of concomitant CIS in bladder cancer was often associated with positive
      ureteral or urethral margin for CIS or invasive carcinoma; therefore,
      intraoperative FS evaluation may be indicated to these patients with concomitant
      bladder CIS. In contrast, in patients with no associated concomitant CIS in the
      bladder, FS of ureteral/urethral margins may not be necessary unless other
      clinical justification is present. 

PMID- 25374919
TI  - Estrogen receptors in prostate development and cancer.
AB  - Prostate cancer (PCa) is an androgen-sensitive disease, which can be
      pharmacologically controlled by androgen blockade. To date, a growing body of
      evidence showed that estrogen and estrogen receptors (ERs) could regulate
      prostate development, as well as cancer initiation and progression. This review
      will address the expression levels and function of ERs in different stages of PCa
      progression. The functions of ERs in different types of prostate cells, the
      ligand effect, and the potential applications of selective estrogen modulators
      (SERMs) will also be discussed. To further dissect ERs' roles in prostate
      development, cell type specific ER knockout mouse models were generated. Results
      collected from the prostate cell type-specific ERalphaKO mouse models provided
      new insights about the cell type specific ERalpha roles in prostate development
      prenatally and postnatally. The results of ERs' roles in mouse PCa mode and the
      correlation of ERs expression and biomedical outcome will also be discussed. 

PMID- 25374921
TI  - PI-3 kinase p110beta: a therapeutic target in advanced prostate cancers.
AB  - Prostate cancers in the castration-resistant stage are life-threatening because
      they are not curable in clinic. The novel androgen receptor inhibitor Xandi
      (Enzalutamide) and the new CYP17 inhibitor Zytiga (Abiraterone) prolonged patient
      survival only a few months in advanced prostate cancers. Therefore, novel
      therapeutic agents for advanced prostate cancers are urgently needed. PI-3
      kinases are major intracellular signaling molecules that regulate multiple signal
      pathways related to cellular metabolism, cytokinesis, growth and survival.
      Accumulating evidence in the literature indicates that some isoforms of this
      kinase family are oncogenic and abnormally expressed in various human cancers,
      including prostate cancers. Recent extensive studies from our group and others
      showed that PI-3 kinase p110beta is aberrantly overexpressed in advanced prostate
      cancers and is critical for prostate cancer development and progression as
      demonstrated in cell-based and animal models. Importantly, novel p110beta
      specific inhibitors have been developed and are currently been testing in
      clinical trials. In this article, we will briefly summarize recent developments
      in this regard. 

PMID- 25374920
TI  - Nuclear receptor corepressor complexes in cancer: mechanism, function and
      regulation.
AB  - Nuclear receptor corepressor (NCoR) and silencing mediator for retinoid and
      thyroid hormone receptors (SMRT) function as corepressors for diverse
      transcription factors including nuclear receptors such as estrogen receptors and
      androgen receptors. Deregulated functions of NCoR and SMRT have been observed in
      many types of cancers and leukemias. NCoR and SMRT directly bind to transcription
      factors and nucleate the formation of stable complexes that include histone
      deacetylase 3, transducin b-like protein 1/TBL1-related protein 1, and G-protein
      pathway suppressor 2. These NCoR/SMRT-interacting proteins also show deregulated
      functions in cancers. In this review, we summarize the literature on the
      mechanism, regulation, and function of the core components of NCoR/SMRT complexes
      in the context of their involvement in cancers and leukemias. While the current
      studies support the view that the corepressors are promising targets for cancer
      treatment, elucidation of the mechanisms of corepressors involved in individual
      types of cancers is likely required for effective therapy. 

PMID- 25374922
TI  - Mechanisms of hemorrhagic cystitis.
AB  - The vast majority of cases of infectious cystitis are easily treated, and most
      patients have no long-term complications. However, hemorrhagic cystitis is a
      potentially deadly complication associated with pelvic radiation therapy,
      chemotherapy, and stem-cell transplant therapy. The focus of current
      understanding, and hence therapy, is directed toward urothelial cell death.
      However, the primary functional ramification of inflammatory bladder disease is
      the loss of compliance due to muscular expansion. Recent studies on smooth muscle
      response in models of bladder inflammation demonstrate a process of pyroptotic
      cell death that potentiates further muscle hyperplasia. These findings may
      support alternative interventions for subjects with hemorrhagic cystitis
      refractive to current therapy. 

PMID- 25374923
TI  - Prostate epithelial stem and progenitor cells.
AB  - The classic androgen ablation and replacement experiment demonstrates that
      prostate epithelia possess extensive regenerative capacities and implies the
      existence of the prostate stem/progenitor cells. These cells may serve as the
      cells of origin for prostate cancer and their intrinsic property may dictate the
      clinical behaviors of the resulting diseases. Therefore, detailed
      characterization of these cells will potentially benefit disease prevention,
      diagnosis and prognosis. In this review, we describe several major in vitro and
      in vivo approaches that have been employed in the studies of the prostate stem
      cell activities, summarize the major progress that has been made during the last
      two decades regarding the identity of prostate stem/progenitor cells and their
      niches, and discuss some remaining outstanding questions in the field. 

PMID- 25374924
TI  - MicroRNAs as predictive biomarkers and therapeutic targets in prostate cancer.
AB  - Prostatectomy or irradiation is the most common traditional treatments for
      localized prostate cancer. In the event of recurrence and/or metastasis, androgen
      ablation therapy has been the mainstay treatment for many years. Although
      initially effective, the cancer inevitably recurs as androgen-independent PCa, a
      disease with limited effective treatments. Enhanced predictive biomarkers are
      needed at the time of diagnosis to better tailor therapies for patients.
      MicroRNAs are short nucleotide sequences which can complementary bind to and
      control gene expression at the post-transcriptional level. Recent studies have
      demonstrated that many miRNAs are variably expressed in cancers vs. normal
      tissues, including PCa. In this review, we summarize PCa-specific miRNAs that
      show potential for their utilization as identifiers of aggressive disease and
      predictors for risk of recurrence. Additionally, we discuss their potential
      clinical applications as biomarkers and therapeutic targets. 

PMID- 25374925
TI  - Proinflammatory cytokine interleukin-6 in prostate carcinogenesis.
AB  - Interleukin-6 (IL-6) is a multifunctional pro-inflammatory cytokine which is
      expressed in clinical specimens obtained from patients with prostate cancer and
      in multiple cell lines. IL-6 expression is regulated in prostate cancer by
      several oncogenes and tumor suppressors. IL-6 activates in prostate cancer
      pathways of Janus kinases/signal transducers and activators of transcription
      (STAT), mitogen-activated protein kinases, and phosphatidylinositol 3-kinase. In
      several tumor models, proliferative and anti-apoptotic effects were described,
      although androgen-sensitive prostate cancer cells LNCaP are inhibited by IL-6. IL
      6 is also involved in regulation of neuroendocrine differentiation and
      angiogenesis in prostate cancer. IL-6 activation of the androgen receptor is
      important for tumor growth and differentiation. IL-6 activation of STAT3 is
      crucial for maintenance of the tumor progenitor cells phenotype. Suppressors of
      cytokine signaling inhibit permanent activation of STAT3, however they may have
      also IL-6-independent effects. Experimental therapies with aim to inhibit IL-6
      signaling in prostate cancer were developed with the monoclonal antibody CNTO328.
      Although progression towards castration resistance was delayed by CNTO328 in a
      xenograft model, clinical monotherapies in patients with castration therapy
      resistant disease with the antibody did not yield a satisfactory response. 

PMID- 25374927
TI  - Significantly higher expression levels of androgen receptor are associated with
      erythroblastosis virus E26 oncogene related gene positive prostate cancer.
AB  - Erythroblastosis virus E26 related gene (ERG) overexpression is correlated with
      the TMPRSS2-ERG fusion gene, a rearrangement known to be present in about 50% of
      cases of prostate cancer. Androgen receptor (AR) is a known regulator of the
      TMPRSS2 gene. Despite knowledge of this relationship, limited data is available
      on the specific relationship of AR expression to TMPRSS2-ERG fusion (ERG) status
      in prostate cancer (PCa). We used multiplexed immunohistochemistry, multispectral
      imaging technology and tissue microarray (TMA) to elucidate this relationship.
      Two prostate tissue microarrays were created from two cohorts of hormonal naive
      patients' prostatectomy specimens: progression TMA (pTMA, from 95 PCa patients)
      and outcome TMA (oTMA, from 183 PCa patients with at least 5-year follow-up
      information). Each of the two TMAs were triple-stained with ERG, AR and E
      cadherin antibodies and visualized with a different chromogen. We found marked
      difference in AR expression levels between ERG positive (ERG(+)) and ERG negative
      (ERG(-)) prostate cancer. The difference was significant in localized (pT2)
      prostate cancer. We also found that AR expression levels were significantly
      higher in PCa tissue compared to benign prostate tissue, with the highest
      expression levels in ERG(+) metastatic cancer. Neither AR nor ERG expression was
      associated with clinical outcome. Our findings confirm that TMPRSS2-ERG fusion is
      AR-dependent and is associated with increased AR expression. Our data suggest
      that the AR pathway may play an important role in the development of ERG(+) PCa
      and ERG status may be useful in stratifying PCa patients for hormonal therapy. 

PMID- 25374926
TI  - TGF-beta induction of FGF-2 expression in stromal cells requires integrated smad3
      and MAPK pathways.
AB  - Transforming Growth Factor-beta (TGF-beta) regulates the reactive stroma
      microenvironment associated with most carcinomas and mediates expression of many
      stromal derived factors important for tumor progression, including FGF-2 and
      CTGF. TGF-beta is over-expressed in most carcinomas, and FGF-2 action is
      important in tumor-induced angiogenesis. The signaling mechanisms of how TGF-beta
      regulates FGF-2 expression in the reactive stroma microenvironment are not
      understood. Accordingly, we have assessed key signaling pathways that mediate TGF
      beta1-induced FGF-2 expression in prostate stromal fibroblasts and mouse embryo
      fibroblasts (MEFs) null for Smad2 and Smad3. TGF-beta1 induced phosphorylation of
      Smad2, Smad3, p38 and ERK1/2 proteins in both control MEFs and prostate
      fibroblasts. Of these, Smad3, but not Smad2 was found to be required for TGF
      beta1 induction of FGF-2 expression in stromal cells. ChIP analysis revealed a
      Smad3/Smad4 complex was associated with the -1.9 to -2.3 kb upstream proximal
      promoter of the FGF-2 gene, further suggesting a Smad3-specific regulation. In
      addition, chemical inhibition of p38 or ERK1/2 MAPK activity also blocked TGF
      beta1-induced FGF-2 expression in a Smad3-independent manner. Conversely,
      inhibition of JNK signaling enhanced FGF-2 expression. Together, these data
      indicate that expression of FGF-2 in fibroblasts in the tumor stromal cell
      microenvironment is coordinately dependent on both intact Smad3 and MAP kinase
      signaling pathways. These pathways and key downstream mediators of TGF-beta
      action in the tumor reactive stroma microenvironment, may evolve as putative
      targets for therapeutic intervention. 

PMID- 25374930
TI  - Genes & Diseases: Moving molecular and translational medicine forward.

PMID- 25374929
TI  - Differential diagnosis of renal tumors with tubulopapillary architecture in
      children and young adults: a case report and review of literature.
AB  - BACKGROUND: Tumors of the kidney are uncommon in children and young adults.
      Accurate classification is crucial for both prognostication and therapeutic
      intervention. However, majority of the tumors in this age group have unusual
      morphology that renders classification challenging. Tubulopapillary architecture
      is one of the most common morphological patterns observed in renal tumors of
      children and young adults. METHODS: A patient with epithelial predominant Wilms
      tumor was reported. Differential diagnosis of renal tumors with tubulopapillary
      morphology was discussed with an emphasis on the histological and
      immunohistochemical features, and the literature was reviewed. RESULTS: A 25 year
      old female patient presented with bilateral multilocular cystic masses. She
      underwent right radical nephrectomy and left partial nephrectomy. The
      pathological examination revealed a tumor with tubulopapillary architecture which
      was lined with low columnar epithelial cells. During the work-up of this case,
      several entities were considered and ruled out by careful gross, microscopic
      examination and prudent use of immunohistochemistry. The tumor cells were
      positive for WT-1, and variably positive for cytokeratin AE1/3, CD56, CD57, and
      negative for cytokeratin 7 and EMA. Fluorescent in-situ hybridization revealed no
      gain of chromosome 7 and 17. A diagnosis of epithelial predominant adult Wilms
      tumors was rendered for both kidneys. The patient received systemic chemotherapy
      and radiation to the remnant left kidney and was free of disease three years
      after the initial surgery. CONCLUSION: The differential diagnosis of renal tumors
      with tubulopapillary features in children and young adults include papillary
      renal cell carcinoma, metanephric adenoma, epithelial predominant Wilms tumor,
      translocation renal cell carcinoma and metastatic adenocarcinoma to the kidney.
      An accurate classification relies on careful examination of clinical and
      pathological features and immunohistochemical characteristics.

PMID- 25374928
TI  - Description and validation of realistic and structured endourology training
      model.
AB  - PURPOSE: The aim of the present study was to validate a model of training, which
      combines the use of non-biological and ex vivo biological bench models, as well
      as the modelling of urological injuries for endourological treatment in a porcine
      animal model. MATERIAL AND METHODS: A total of 40 participants took part in this
      study. The duration of the activity was 16 hours. The model of training was
      divided into 3 levels: level I, concerning the acquisition of basic theoretical
      knowledge; level II, involving practice with the bench models and level III,
      concerning practice in the porcine animal model. First, trainees practiced with
      animals without using a model of injured (ureteroscopy, management of guide wires
      and catheters under fluoroscopic control) and later practiced in lithiasic animal
      model. During the activity, an evaluation of the face and content validity was
      conducted, as well as constructive validation provided by the trainees versus
      experts. Evolution of the variables during the course within each group was
      analysed using the Student's t test for paired samples, while comparisons between
      groups, were performed using the Student's t test for unpaired samples. RESULTS:
      The assessments of face and content validity were satisfactory. The constructive
      validation, "within one trainee" shows that were statistical significant
      differences between the first time the trainees performed the tasks in the animal
      model and the last time, mainly in the knowledge of procedure and Holmium laser
      lithotripsy cathegories. At the beginning of level III, there are also
      statistical significant differences between trainee's scores and the expert's
      scores. CONCLUSIONS: This realistic Endourology training model allows the
      acquisition of knowledge and technical and non-technical skills as evidenced by
      the face, content and constructive validity. Structured use of bench models
      (biological and non biological) and animal model simulators increase the
      endourological basic skills.

PMID- 25374931
TI  - CRISPR clear? Dimeric Cas9-Fok1 nucleases improve genome-editing specificity.

PMID- 25374932
TI  - Nutritional and hygienic quality of raw milk in the mid-northern region of
      Algeria: correlations and risk factors.
AB  - This paper aims to study the overall quality of raw milk in the mid-northern
      region of Algeria. The analysis results showed a decrease in the average
      temperature for the delivery of 1,54 degrees C with P<0.001. However, no
      significant variation (P>0.05) was observed in almost all the physical and
      nutritional parameters studied (pH, fat content, and protein content) between M1
      and M2. The average contamination by total mesophilic aerobic bacteria (TMAB),
      coliforms, yeasts, molds, and different pathogens in samples taken at M1 showed
      significant changes at M2. This was confirmed by the decrease of reduction time
      of methylene blue (RTMB), about 54%. The variation was described as follows:
      (P>0.05) for yeasts and (P<0.05) for molds in M1 and M2, (P<0.05) for TMAB in M1,
      and (P<0.001) for TC, FC, and TMAB in M2. The analysis for the detection of
      Salmonella spp. showed no contamination in all samples tested, while antibiotic
      residues were detected in 35% of milks delivered. In conclusion, several risk
      factors have been identified in this study, namely, the effect of the season and
      the distance between the farm and the dairy unit.

PMID- 25374933
TI  - On the general Dedekind sums and two-term exponential sums.
AB  - We use the analytic methods and the properties of Gauss sums to study the
      computational problem of one kind hybrid mean value involving the general
      Dedekind sums and the two-term exponential sums, and give an interesting
      computational formula for it. 

PMID- 25374934
TI  - Environmentally related diseases and the possibility of valuation of their social
      costs.
AB  - The risks of the morbidity of the asbestos-related lung cancer was estimated in
      the general population of Poles as the result of increased exposure to asbestos
      fibers during the removal of asbestos-cement products and the possibility of the
      valuation of the social costs related to this risk. The prediction of the new
      incidences was made using linear regression model. The forecast shows that to the
      end of 2030 about 3,500 new cases of lung cancer can be expected as a result of
      occupational exposure to asbestos in the past which makes together with
      paraoccupational exposure about 14.000 new cases. The forecast shows the
      increasing number of asbestos-related lung cancer in Poland and indicates the
      priority areas where preventive action should be implemented. 

PMID- 25374936
TI  - Soft mappings space.
AB  - Various soft topologies are being introduced on a given function space soft
      topological spaces. In this paper, soft compact-open topology is defined in
      functional spaces of soft topological spaces. Further, these functional spaces
      are studied and interrelations between various functional spaces with soft
      compact-open topology are established. 

PMID- 25374935
TI  - Arsenic contamination of groundwater: a review of sources, prevalence, health
      risks, and strategies for mitigation.
AB  - Arsenic contamination of groundwater in different parts of the world is an
      outcome of natural and/or anthropogenic sources, leading to adverse effects on
      human health and ecosystem. Millions of people from different countries are
      heavily dependent on groundwater containing elevated level of As for drinking
      purposes. As contamination of groundwater, poses a serious risk to human health.
      Excessive and prolonged exposure of inorganic As with drinking water is causing
      arsenicosis, a deteriorating and disabling disease characterized by skin lesions
      and pigmentation of the skin, patches on palm of the hands and soles of the feet.
      Arsenic poisoning culminates into potentially fatal diseases like skin and
      internal cancers. This paper reviews sources, speciation, and mobility of As and
      global overview of groundwater As contamination. The paper also critically
      reviews the As led human health risks, its uptake, metabolism, and toxicity
      mechanisms. The paper provides an overview of the state-of-the-art knowledge on
      the alternative As free drinking water and various technologies (oxidation,
      coagulation flocculation, adsorption, and microbial) for mitigation of the
      problem of As contamination of groundwater. 

PMID- 25374937
TI  - An approach to differential diagnosis of antiphospholipid antibody syndrome and
      related conditions.
AB  - The antiphospholipid antibody syndrome is a systemic, acquired, immune-mediated
      disorder characterized by episodes of venous, arterial, or microcirculation
      thrombosis and/or pregnancy abnormalities, associated with the persistent
      presence of autoantibodies, confirmed at least in two occasions 12 weeks apart,
      directed to molecular complexes consisting of phospholipids and proteins.
      Antiphospholipid antibody syndrome should always be considered as a potential
      diagnosis especially for young patients presenting with a history of thrombotic
      events, in particular when they occur without any obvious external trigger or any
      inherited thrombophilic mutation (even if 2006 criteria do not exclude
      antiphospholipid antibody syndrome in patients with other inherited or acquired
      prothrombotic conditions), or for women with recurrent pregnancy losses or later
      fetal deaths. Many other disorders are able to mimic antiphospholipid antibody
      syndrome, so a broad range of alternative diagnoses should be investigated and
      ruled out during clinical workup. 

PMID- 25374938
TI  - Incidence and evaluation of incidental abnormal bone marrow signal on magnetic
      resonance imaging.
AB  - PURPOSE: The increased use of magnetic resonance imaging (MRI) has resulted in
      reports of incidental abnormal bone marrow (BM) signal. Our goal was to determine
      the evaluation of an incidental abnormal BM signal on MRI and the prevalence of a
      subsequent oncologic diagnosis. METHODS: We conducted a retrospective cohort
      study of patients over age 18 undergoing MRI between May 2005 and October 2010 at
      Tufts Medical Center (TMC) with follow-up through November 2013. The electronic
      medical record was queried to determine imaging site, reason for scan, evaluation
      following radiology report, and final diagnosis. RESULTS: 49,678 MRIs were done
      with 110 patients meeting inclusion criteria. Twenty two percent underwent some
      evaluation, most commonly a complete blood count, serum protein electrophoresis,
      or bone scan. With median follow-up of 41 months, 6% of patients were diagnosed
      with malignancies including multiple myeloma, non-Hodgkins lymphoma, metastatic
      non-small cell lung cancer, and metastatic adenocarcinoma. One patient who had
      not undergone evaluation developed breast cancer 24 months after the MRI.
      CONCLUSIONS: Incidentally noted abnormal or heterogeneous bone marrow signal on
      MRI was not inconsequential and should prompt further evaluation.

PMID- 25374939
TI  - Estimating the concrete compressive strength using hard clustering and fuzzy
      clustering based regression techniques.
AB  - Understanding of the compressive strength of concrete is important for activities
      like construction arrangement, prestressing operations, and proportioning new
      mixtures and for the quality assurance. Regression techniques are most widely
      used for prediction tasks where relationship between the independent variables
      and dependent (prediction) variable is identified. The accuracy of the regression
      techniques for prediction can be improved if clustering can be used along with
      regression. Clustering along with regression will ensure the more accurate curve
      fitting between the dependent and independent variables. In this work cluster
      regression technique is applied for estimating the compressive strength of the
      concrete and a novel state of the art is proposed for predicting the concrete
      compressive strength. The objective of this work is to demonstrate that
      clustering along with regression ensures less prediction errors for estimating
      the concrete compressive strength. The proposed technique consists of two major
      stages: in the first stage, clustering is used to group the similar
      characteristics concrete data and then in the second stage regression techniques
      are applied over these clusters (groups) to predict the compressive strength from
      individual clusters. It is found from experiments that clustering along with
      regression techniques gives minimum errors for predicting compressive strength of
      concrete; also fuzzy clustering algorithm C-means performs better than K-means
      algorithm. 

PMID- 25374940
TI  - Water wave solutions of the coupled system Zakharov-Kuznetsov and generalized
      coupled KdV equations.
AB  - An analytic study was conducted on coupled partial differential equations. We
      formally derived new solitary wave solutions of generalized coupled system of
      Zakharov-Kuznetsov (ZK) and KdV equations by using modified extended tanh method.
      The traveling wave solutions for each generalized coupled system of ZK and KdV
      equations are shown in form of periodic, dark, and bright solitary wave
      solutions. The structures of the obtained solutions are distinct and stable. 

PMID- 25374941
TI  - Phytochemical and biological activities of four wild medicinal plants.
AB  - The fruits of four wild plants, namely, Capparis decidua, Ficus carica, Syzygium
      cumini, and Ziziphus jujuba, are separately used as traditional dietary and
      remedial agents in remote areas of Khyber Pakhtunkhwa, Pakistan. The results of
      our study on these four plants revealed that the examined fruits were a valuable
      source of nutraceuticals and exhibited good level of antimicrobial activity. The
      fruits of these four investigated plants are promising source of polyphenols,
      flavonoids, alkaloids, terpenoids, and saponins. These four plants' fruits are
      good sources of iron, zinc, copper, manganese, selenium, and chromium. It was
      also observed that these fruits are potential source of antioxidant agent and the
      possible reason could be that these samples had good amount of phytochemicals.
      Hence, the proper propagation, conservation, and chemical investigation are
      recommended so that these fruits should be incorporated for the eradication of
      food and health related problems. 

PMID- 25374942
TI  - Reproductive toxicity of triptolide in male house rat, Rattus rattus.
AB  - The aim of study was to investigate the toxic effect of triptolide fed in bait on
      reproduction of male house rat, Rattus rattus. Feeding of cereal based bait
      containing 0.2% triptolide to male R. rattus for 5 days in no-choice feeding
      test, leading to mean daily ingestion of 20.45 mg/kg bw of triptolide, was found
      effective in significantly (P <= 0.05) reducing sperm motility and viability in
      cauda epididymal fluid by 80.65 and 75.14%, respectively, from that of untreated
      rats. Pregnancy rates were decreased by 100% in untreated cyclic female rats
      paired with male rats treated with 0.2% triptolide. Present studies suggest the
      potential of 0.2% triptolide bait in regulating reproductive output of R. rattus.

PMID- 25374943
TI  - Trust-based access control model from sociological approach in dynamic online
      social network environment.
AB  - There has been an explosive increase in the population of the OSN (online social
      network) in recent years. The OSN provides users with many opportunities to
      communicate among friends and family. Further, it facilitates developing new
      relationships with previously unknown people having similar beliefs or interests.
      However, the OSN can expose users to adverse effects such as privacy breaches,
      the disclosing of uncontrolled material, and the disseminating of false
      information. Traditional access control models such as MAC, DAC, and RBAC are
      applied to the OSN to address these problems. However, these models are not
      suitable for the dynamic OSN environment because user behavior in the OSN is
      unpredictable and static access control imposes a burden on the users to change
      the access control rules individually. We propose a dynamic trust-based access
      control for the OSN to address the problems of the traditional static access
      control. Moreover, we provide novel criteria to evaluate trust factors such as
      sociological approach and evaluate a method to calculate the dynamic trust
      values. The proposed method can monitor negative behavior and modify access
      permission levels dynamically to prevent the indiscriminate disclosure of
      information. 

PMID- 25374944
TI  - What is the role of hysteroscopic surgery in the management of female
      infertility? A review of the literature.
AB  - The position of hysteroscopy in current fertility practice is under debate. There
      are many randomized controlled trials on technical feasibility and patient
      compliance demonstrating that the procedure is well tolerated and effective in
      the treatment of intrauterine pathologies. However, no consensus on the
      effectiveness of hysteroscopic surgery in improving the prognosis of subfertile
      women is available. A literature review was performed to explore the available
      information regarding the role of hysteroscopy in the evaluation and management
      of female infertility as well as to ascertain evidence that treatment of these
      uterine abnormalities improves fertility. The debate regarding the role of
      hysteroscopic surgery in the management of female infertility remains as the
      published studies did not reach a consensus on the benefit of such an
      intervention in this setting. The randomized trials do not clearly demonstrate
      that surgical correction of all intrauterine abnormalities improves IVF outcome.
      However, published observational studies suggest a benefit for resection of
      submucosal leiomyomas, adhesions, and endometrial polyps in increasing pregnancy
      rates. More randomised controlled studies are needed to substantiate the
      effectiveness of the hysteroscopic removal of suspected intrauterine pathology in
      women with unexplained subfertility or prior to assisted reproductive technology.

PMID- 25374945
TI  - Solitary fibrous tumour of the pleura presenting as a spontaneous massive
      haemothorax.
AB  - Solitary fibrous tumours of the pleura are rare neoplasms. These tumours are
      generally asymptomatic and incidentally diagnosed. Symptoms, if present, are
      nonspecific such as cough, dyspnea, and chest pain. This report describes the
      case of a 38-year-old woman admitted to our department after the onset of a right
      massive spontaneous haemothorax requiring emergency surgical treatment.
      Intraoperatively a bleeding pleural mass was found to be the cause of the
      haemothorax. The tumour was successfully resected and the patient made an
      uneventful recovery. Histological examination revealed the mass to be a solitary
      fibrous tumour of the pleura. 

PMID- 25374946
TI  - Complications following Treatment of Trochanteric Fractures with the Gamma3 Nail:
      Is the Latest Version of Gamma Nail Superior to Its Predecessor?
AB  - Gamma nail is a cephalomedullary implant that was developed for the treatment of
      pertrochanteric hip fractures and has been successfully used for over 20 years.
      During this period, modifications of design and instrumentation have occurred to
      combat the intra- and postoperative complications that were associated with the
      use of early designs. The purpose of this study was to compare the complications
      observed with the use of the Gamma3 nail (G3N) with those seen following use of
      the previous trochanteric gamma nail (TGN). This study prospectively recorded the
      intra- and postoperative complications of 175 patients treated with the Gamma3
      nail and compared them with those of a historical cohort of 192 patients treated
      with the trochanteric gamma nail. We encountered less intra- and postoperative
      complications with the use of Gamma3 nail. Femoral fractures and lag screw cutout
      were significantly lower. The reoperation rate was significantly higher in the
      TGN group. Gamma3 nail has proved to be a safe and efficient implant for the
      treatment of pertrochanteric fractures. The improvement of the biomechanical
      characteristics has led to a significant decrease in complication rates,
      demonstrating superiority over its predecessor. 

PMID- 25374947
TI  - PET/CT Is Complementary to Fine-Needle Aspiration Cytology in Assessment of
      Irradiated Neck in Head and Neck Cancers.
AB  - Background. Accurate assessment of irradiated neck in squamous cell carcinoma of
      the head and neck (HNSCC) is essential. Fine-needle aspiration cytology is often
      performed for suspicious lesions but it is limited by its low negative predictive
      value (NPV). We postulated that F-18 fluorodeoxyglucose (FDG) positron emission
      tomography combined with computed tomography (PET/CT) can overcome this
      limitation by its high NPV value and allow for a more accurate assessment of
      irradiated neck in HNSCC. Methods. Fifty-four HNSCC patients were included for
      the study. They all received previous irradiation to the neck. Clinical
      characteristics, details of radiotherapy, PET/CT results, follow-up findings, and
      final histological diagnosis were analyzed. Results. The sensitivity,
      specificity, positive predictive value (PPV), and NPV were 95.8%, 96.7%, 95.8%,
      and 96.7%, respectively. Age, sex, radiation dose, interval between PET/CT and
      radiotherapy completion, nature of radiotherapy, and use of second course of
      radiotherapy were not found to affect diagnostic accuracy of PET/CT. A new
      algorithm for investigation of masses in irradiated neck is proposed.
      Conclusions. PET/CT is an effective diagnostic tool and has a complementary role
      to FNAC in the management of irradiated neck in head and neck cancers,
      particularly in cases where suspicious lesions were identified but FNAC showed
      negative results. 

PMID- 25374948
TI  - Patient aesthetic satisfaction with timing of nasal fracture manipulation.
AB  - Introduction. To determine patient cosmetic satisfaction following nasal fracture
      manipulation under general anaesthetic when offered at different time intervals
      after injury. Materials and Methods. Prospective chart review of adult patients
      with nasal fractures treated by closed reduction at a busy district general
      hospital in Greater London over a 10-month period. Patients were asked by a
      standardised telephone interview about satisfaction with nasal cosmesis pre- and
      postoperatively using a Likert scale. Results. Seventy-six of 106 patients
      presented for nasal manipulation at up to 9 weeks after injury and were
      successfully contacted (72%) postoperatively. Forty-nine patients (64%) reported
      that they still would have had the surgery in retrospect. Those done within 1-2
      weeks after injury resulted in the highest mean satisfaction score (4.56 +/-
      0.25). There was a negative correlation between patient satisfaction and timing
      of surgery (rho = -0.37, P = 0.001). Of the patients satisfied or very satisfied
      with their procedure, 96% had it done within 4 weeks. Conclusion. The majority of
      patients treated with closed reduction of nasal fractures under general
      anaesthetic are satisfied with the cosmetic outcome and would still have
      undergone surgery in retrospect. Increasing time of surgery after 2 weeks
      resulted in lower patient satisfaction. 

PMID- 25374949
TI  - Management of superficial abscesses: scope for day case surgery.
AB  - Background. Patients presenting with superficial abscesses are often regarded as
      low priority and given a less efficient service. Aim. The aim of this study was
      to investigate the efficiency of emergency treatment of superficial abscesses and
      to identify areas for service improvement. Method. A retrospective case review of
      patients admitted to Derriford Hospital, Plymouth, over a four-month period.
      Results. Ninety-seven patients were included in the study. Seventy two (74%)
      arrived between 08.00 and 16.00 hours. Overall, 75 patients (77%) were referred
      on weekdays with 22 patients (23%) during weekends. Seventy-two patients (74%)
      had treatment under a general anaesthetic. Sixty-three percent of operations
      occurred within the working day. The time interval between admission and surgery
      ranged from 52 minutes to 38 hours (mean +/- SD 16 +/- 9.15). The length of
      admission ranged from 5.3 hours to 11 days (mean 36 hours). Of the one hundred
      overnight beds used by the 97 patients, 30 nights were spent awaiting surgery and
      70 following surgery and awaiting discharge. Conclusion. Eighty-nine percent of
      the patients would have been suitable for treatment as day cases. This review
      shows that a simple service redesign has the potential of reducing inpatient bed
      occupancy and improving the patient's journey. 

PMID- 25374950
TI  - Six-year experience of a nurse-led colorectal cancer follow-up clinic.
AB  - Aims and Objectives. To review the experience of a nurse-led colorectal cancer
      follow-up clinic in a tertiary referral colorectal cancer centre. Methodology.
      Data from the nurse-led colorectal cancer follow-up clinic in our unit was
      prospectively maintained in a colorectal cancer database. Data was analysed from
      January 1, 2006 until the December 31, 2011. Results. 1125 patients were
      diagnosed with colorectal cancer, and referred to our unit as a tertiary centre
      for specialised colorectal cancer. Nine hundred and four patients had surgical
      resection of their colorectal cancer. Four hundred and seven patients were
      referred to the nurse-led colorectal cancer clinic for surveillance. The mean age
      of the patient cohort was 67 years (range 32-88) and 56% of patients were male.
      One hundred and seventeen patients were discharged to their general practitioner
      having been disease free after 5 years of followup. Fifty-four patients were
      diagnosed with either local or distant recurrence. Conclusion. A nurse-led
      colorectal cancer follow-up clinic is running according to strict follow-up
      protocols. This type of clinic significantly reduces the number of routine follow
      up patients that have to be seen by the colorectal surgical consultant. 

PMID- 25374951
TI  - Endoscopic Endonasal Transsphenoidal Resection for Pituitary Apoplexy during the
      Third Trimester of Pregnancy.
AB  - Pituitary apoplexy is an uncommon phenomenon typically characterized by vascular
      insufficiency or acute hemorrhage into a pituitary adenoma. The overall incidence
      of pituitary apoplexy ranges between 1 and 25% of all pituitary adenomas. With
      the widespread use of MRI technology, the diagnosis of asymptomatic intratumoral
      hemorrhage is closer to 10%. The authors report a case of a 27-year-old female in
      her 36th week of pregnancy who presented with severe onset headache and acute
      left-sided vision loss. MRI of the brain revealed a large hemorrhagic mass
      occupying the sella turcica. The patient underwent an emergent endoscopic
      endonasal transsphenoidal resection for pituitary apoplexy. Postoperatively, the
      patient's neurologic deficit resolved. Minimally invasive endoscopic endonasal
      transsphenoidal resection of pituitary apoplexy can be safely utilized in third
      trimester pregnant women presenting with acute severe neurologic deficits. 

PMID- 25374952
TI  - The Use of the S-MART Tourniquet in Hand Surgery: A Safe and Effective Way to
      Provide a Bloodless Field.
AB  - We have retrospectively reviewed our use of the S-MART sterile silicon ring self
      exsanguinating tourniquet in 300 consecutive minor hand surgical procedures. A
      total of 3 postoperative complications were identified, only 1 of which was
      directly related to the tourniquet's use. We outline the reasons of why we feel
      that this device provides a safe and effective bloodless field and the benefits
      of its use. 

PMID- 25374953
TI  - Deltopectoral flap in the era of microsurgery.
AB  - Background. Our study aimed to review the role of deltopectoral (DP) flap as a
      reconstructive option for defects in the head and neck region in the
      microvascular era. Methods. All patients who received DP flap reconstruction
      surgery at the Department of Surgery, Queen Mary Hospital, between 1999 and 2011
      were recruited. Demographic data, indications for surgery, defect for
      reconstruction, and surgical outcomes were analyzed. Results. Fifty-four patients
      were included. All but two patients were operated for reconstruction after tumour
      resection. The remaining two patients were operated for necrotizing fasciitis and
      osteoradionecrosis. The majority of DP flaps were used to cover neck skin defect
      (63.0%). Other reconstructed defects included posterior pharyngeal wall (22.2%),
      facial skin defect (11.1%), and tracheal wall (3.7%). All donor sites were
      covered with partial thickness skin graft. Two patients developed partial flap
      necrosis at the tip and were managed conservatively. The overall flap survival
      rate was 96.3%. Conclusions. Albeit the technical advancements in microvascular
      surgery, DP still possesses multiple advantages (technical simplicity, reliable
      axial blood supply, large size, thinness, and pliability) which allows it to
      remain as a useful, reliable, and versatile surgical option for head and neck
      reconstruction. 

PMID- 25374954
TI  - Glomus jugulare presenting with isolated facial nerve palsy.
AB  - Glomus jugulare is a rare slow growing tumor occurring within the jugular foramen
      that rarely presents with isolated symptoms. Although histologically benign,
      these tumors are locally destructive because of their proximity to the petrous
      bone, the lower cranial nerves, and the major vascular structures (Miller et al.
      (2009) and Silverstone (1973)). We wish to report a glomus jugulare tumor eroding
      the petrous bone and producing an ipsilateral peripheral facial weakness. The
      mechanism of this erosion is discussed. 

PMID- 25374955
TI  - Perioperative avulsion of a left internal mammary artery graft in a patient with
      syphilis.
AB  - Avulsion of a graft after coronary artery bypass grafting surgery is a rare but
      very serious complication which leads to massive bleeding and possible life
      threatening cardiac tamponade. In this paper we report a very rare case of a left
      internal mammary artery graft avulsion on the day of surgery in a patient with
      syphilis. 

PMID- 25374956
TI  - Modern management of the exstrophy-epispadias complex.
AB  - The exstrophy-epispadias complex is a rare spectrum of malformations affecting
      the genitourinary system, anterior abdominal wall, and pelvis. Historically,
      surgical outcomes were poor in patients with classic bladder exstrophy and
      cloacal exstrophy, the two more severe presentations. However, modern techniques
      to repair epispadias, classic bladder exstrophy, and cloacal exstrophy have
      increased the success of achieving urinary continence, satisfactory cosmesis, and
      quality of life. Unfortunately, these procedures are not without their own
      complications. This review provides readers with an overview of the management of
      the exstrophy-epispadias complex and potential surgical complications. 

PMID- 25374957
TI  - Melanoma of the urinary bladder: a review of the literature.
AB  - Background. Melanomas of the urinary bladder and urethra are rare. Aims. To
      review the literature on the disease. Methods. Various Internet databases were
      used to identify reported cases of the disease. Results. Less than 30 cases of
      primary melanoma of the urinary bladder and urethra have been reported in the
      literature and they have been associated with melanosis and commonly with
      metastases. The lesions may be primary or metastatic with no gender preference.
      The diagnostic features include pigmented raised lesions which histologically
      exhibit spindled or epitheliod cells, necrosis, mitotic figures, and atypical
      melanocytes. Immunohistochemically they stain positively with S100; HMB45; and
      other melanocyte markers, but negatively with Keratin and Vimentin. The treatment
      involves excision and possibly IL-2. The prognostic factors include size and
      depth of invasion as well as metastatic lesions. Conclusions. Less than 30 cases
      (about 24 cases) of the disease have been reported. There are also reports of
      metastatic melanomas of the urinary bladder emanating from primary melanomas
      originating elsewhere. Diagnosis of the primary disease is based upon the
      histological appearance of the lesion, positive staining with S100 and HMB45, and
      evidence of absence of melanoma elsewhere. Primary melanoma of the bladder is
      usually a fatal lesion. 

PMID- 25374958
TI  - Bilateral psoas haematomata complicating renal transplantation.
AB  - Background. The challenge in managing patients undergoing renal transplantation
      is how to achieve optimum levels of anticoagulation to avoid both clotting and
      postoperative bleeding. We report a rare case of severe postoperative
      retroperitoneal bleeding including psoas haematomata complicating renal
      transplantation. Case Report. SM, a 55-year-old female, had a past history of
      aortic valve replacement, cerebrovascular event, and thoracic aortic aneurysm and
      was on long-term warfarin that was switched to enoxaparin 60 mg daily a week
      prior to her living donor transplantation. Postoperatively, she was started on a
      heparin infusion, but this was complicated by a large retroperitoneal bleed
      requiring surgical evacuation on the first postoperative day. Four weeks later,
      she developed features compatible with acute femoral neuropathy and a CT scan
      revealed bilateral psoas haematomata. Following conservative management, she made
      steady progress and was discharged home via a community hospital 94 days after
      transplantation. At her last visit 18 months after transplantation, she had
      returned to full fitness with excellent transplant function. Conclusion. Patients
      in established renal failure who require significant anticoagulation are at
      increased risk of bleeding that may involve prolonged hospitalisation and more
      protracted recovery and patients should be carefully counselled about this. 

PMID- 25374959
TI  - Resection leads to less recurrence than strictureplasty in a paediatric
      population with obstructive Crohn's disease.
AB  - Introduction. Resection and strictureplasty are used to treat patients with
      obstructive Crohn's disease. Strictureplasty is preferable in adults as it
      retains bowel length. This study aims to identify differences in outcomes of
      children undergoing strictureplasty and resection for obstructive Crohn's
      disease. Method. Patients under 20 years undergoing surgery over a nine-year
      period were included. Data was collected on procedures for stenotic Crohn's
      disease. Patients were divided into 2 groups: Group 1 treated with
      strictureplasties and Group 2 resections. Postoperative complications and
      recurrence rates were recorded. Kaplan-Meier method was used to analyze the data.
      Results. Twenty-six patients and 40 operations were identified. Mean age was 15.6
      years (7.2-19.4) with equal numbers of males and females. Mean follow-up was 45.9
      months (0.1-149.9). 20/40 procedures involved the terminal ileum; 9/40, the
      ileocolic junction; 8/40, the upper GI tract; and 3/40, the colon. Group 1
      consisted of 19 strictureplasties and Group 2 consisted of 13 resections and 8
      combined procedures. Significantly more patients in Group 1 required further
      surgery (11/19 versus 3/21; P = 0.008). Conclusion. Allowing for variations in
      disease duration, severity, and previous medical management, these data suggest
      that resection is preferable to strictureplasty in treating obstructive Crohn's
      disease in children and adolescents. 

PMID- 25374960
TI  - Coronary artery bypass graft surgery: the past, present, and future of myocardial
      revascularisation.
AB  - The development of the heart-lung machine ushered in the era of modern cardiac
      surgery. Coronary artery bypass graft surgery (CABG) remains the most common
      operation performed by cardiac surgeons today. From its infancy in the 1950s till
      today, CABG has undergone many developments both technically and clinically.
      Improvements in intraoperative technique and perioperative care have led to CABG
      being offered to a more broad patient profile with less complications and adverse
      events. Our review outlines the rich history and promising future of myocardial
      revascularization. 

PMID- 25374961
TI  - A Comparative Study between the Outcome of Primary Repair versus Loop Ileostomy
      in Ileal Perforation.
AB  - Introduction. Ileal perforation peritonitis is a common surgical emergency in the
      Indian subcontinent and in tropical countries. It is reported to constitute the
      fifth common cause of abdominal emergencies due to high incidence of enteric
      fever and tuberculosis in these regions. Methods. Sixty proven cases of ileal
      perforation patients admitted to Surgical Emergency were taken up for emergency
      surgery. Randomisation was done by senior surgeons by picking up card from both
      the groups. The surgical management was done as primary repair (group A) and loop
      ileostomy (group B). Results. An increased rate of postoperative complications
      was seen in group A when compared with group B with 6 (20%) patients landed up in
      peritonitis secondary to leakage from primary repair requiring reoperation as
      compared to 2 (6.67%) in ileostomy closure. A ratio of 1 : 1.51 days was observed
      between hospital stay of group A to group B. Conclusion. In cases of ileal
      perforation temporary defunctioning loop ileostomy plays an important role. We
      recommend that defunctioning ileostomy should be preferred over other surgical
      options in cases of ileal perforations. It should be recommended that ileostomy
      in these cases is only temporary and the extra cost and cost of management are
      not more than the price of life. 

PMID- 25374962
TI  - Nonfunctional Metastatic Parathyroid Carcinoma in the Setting of Multiple
      Endocrine Neoplasia Type 2A Syndrome.
AB  - Parathyroid carcinoma is a very rare malignancy. It has been associated with
      hyperparathyroidism-jaw tumour syndrome, familial isolated primary
      hyperparathyroidism, and multiple endocrine neoplasia type 1 (MEN-1) and 2A (MEN
      2A) syndromes. We report a 54-year-old man with a MEN-2A which presents with a
      nonfunctional metastatic parathyroid carcinoma and a pheochromocytoma in the
      absence of medullary thyroid carcinoma. Only a few cases of parathyroid carcinoma
      have been reported in the literature associated with this syndrome. 

PMID- 25374964
TI  - EFFECTS OF ENVIRONMENTAL FACTORS ON NATURALISTIC DRIVING IN OBSTRUCTIVE SLEEP
      APNEA.
AB  - Reduced visibility and other environmental factors can impair driver ability to
      respond to roadway hazards. We examined the effects of reduced visibility on
      naturalistic driving in 66 drivers, including 45 at-risk drivers with obstructive
      sleep apnea (OSA) and 21 controls. We analyzed three months of electronic data
      using "black box" recorder technology and assessed the extent to which driver
      speed, longitudinal acceleration, and lateral acceleration metrics depend on
      ambient visibility from web-based environmental data archives. We calculated
      summary driving metrics within 10-second intervals, and reduced these to within
      subject means and tested for associations of interest. OSA drivers did not differ
      from controls with respect to electronic measures or visibility conditions in
      which they drove. On average, drivers drove slower when visibility was reduced.
      After controlling for speed, variations in lateral and longitudinal acceleration
      were positively associated with high-visibility conditions. These findings
      suggest that drivers exert greater vehicular control when visibility is limited,
      and that this association is not just due to slower speeds. Weaker relationships
      between visibility and driving measures in OSA suggest reduced adaptive
      strategies. Our methods provide a framework for analyzing the effects of other
      environmental factors on driving, and we provide an additional example using wind
      speed.

PMID- 25374963
TI  - Negative Effects of Time in Bed Extension: A Pilot Study.
AB  - Epidemiologic studies have consistently shown an association of long sleep (>=8
      hr) with mortality and multiple morbidities. However, there has been little
      experimental investigation of the effects of sleep extension. The aim of this
      study was to examine the effects of time in bed (TIB) extension, on depression,
      anxiety, sleepiness, and systemic inflammation. Following baseline, 14 healthy
      sleepers (31.79+/-10.94 years) were randomized to one of two one-week treatments:
      (1) a TIB extension treatment involving a fixed sleep schedule in which TIB was
      increased by 3 hours/night compared with the participants' median baseline TIB;
      (2) a control treatment involving a fixed schedule in which TIB was the same as
      the participants' median baseline TIB. Actigraphic recording of sleep was
      assessed throughout both weeks. Self-reported depression, state anxiety,
      sleepiness, and sleep quality, as well as blood pressure, and inflammation were
      assessed at baseline and following the treatment week. Compared with baseline,
      TIB increased by 127.12+/-3.92 min and total sleep time increased by 119.88+/
      18.52 min during TIB extension, but decreased slightly in the control treatment.
      Depression was elevated more following TIB extension (effect size (ES)=-0.86) vs.
      control (ES=-0.50). Interleukin-6 levels increased by 2-fold following TIB
      extension (ES=-0.65), but did not change following the control treatment.
      Sleepiness increased after TIB extension, but decreased after the control
      treatment. The results revealed negative effects of TIB extension on mood and
      inflammation. Larger-scale studies involving more prolonged, but less profound
      sleep extension, are warranted.

PMID- 25374965
TI  - Albiglutide for the treatment of type 2 diabetes.
AB  - The glucagon-like peptide 1 (GLP-1) receptor agonists are a new class of
      antidiabetic drugs that provide the benefits of decreasing HbA1c and plasma
      glucose concentrations, stimulating insulin secretion with a very low risk of
      hypoglycemia, and promoting weight loss. With the exception of once-weekly
      exenatide, currently available GLP-1 receptor agonists are administered once or
      twice daily by injection. Albiglutide is a new GLP-1 receptor agonist recently
      approved in the U.S. (TanzeumTM) and European Union (Eperzan(r)) for the
      treatment of patients with type 2 diabetes with a dosage of 30 mg once weekly,
      which may be increased to 50 mg if the glycemic response is inadequate. Clinical
      trials showed that albiglutide once weekly delayed gastric emptying, mildly
      decreased body weight and had similar efficacy in the reduction of HbA1c as
      comparators, but it failed to demonstrate noninferiority to liraglutide.
      Albiglutide exhibits an acceptable safety profile, although it is associated with
      more frequent gastrointestinal complaints (e.g., nausea, diarrhea, vomiting) and
      injection-site reactions. Immunogenicity (i.e., testing positive for anti-drug
      antibody) was observed in 5.5% of subjects but it was not associated with
      increased adverse events. Long-term studies are needed to fully assess potential
      adverse events. 

PMID- 25374966
TI  - Panitumumab in the treatment of colon cancer: A biomarker dilemma.
AB  - Panitumumab is a fully human monoclonal antibody targeting epidermal growth
      factor receptor (EGFR) approved for use in colorectal cancer (CRC). Critical
      information regarding biomarkers in CRC has been discovered through the
      investigation of panitumumab treatment. The discovery of anti-EGFR resistance in
      the setting of Kirsten rat sarcoma viral oncogene (KRAS) and more recently,
      neuroblastoma RAS viral oncogene (NRAS) mutations in CRC has changed the focus of
      therapy for metastatic disease to one based on the molecular characteristics of
      the tumor. This review will give a brief background on panitumumab and its
      current uses in CRC. 

PMID- 25374967
TI  - A report from the American Society for Bone and Mineral Research 2014 Annual
      Meeting (September 12-15 - Houston, Texas, USA).
AB  - Although the weather was very Texas-unlike, with fog, clouds and even intense
      rain, the George R. Brown Convention Center in Houston was the site for this
      year's annual meeting of the American Society for Bone and Mineral Research,
      where investigators from across the world came to present the latest findings in
      bone science. Four days of oral and poster presentations encompassing over 1,500
      papers discussing a great variety of subjects including preclinical and clinical
      research aimed at improving the treatment of bone diseases such as osteoporosis
      and other forms of bone frailty. 

PMID- 25374968
TI  - A report from the 50th Annual Meeting of the European Association for the Study
      of Diabetes (EASD) (September 15-19, 2014 - Vienna, Austria).
AB  - Since its foundation in 1965, the European Association for the Study of Diabetes
      (EASD) has been organizing an annual meeting, which has become the largest
      international annual conference on diabetes research worldwide. This year, the
      50th edition was held in Vienna, Austria, from September 15 to 19. A total of
      1,332 abstracts were accepted for inclusion and the program comprised 6 parallel
      tracks, which included stimulating symposia, keynote lectures and debates
      covering basic and clinical science. The EASD meeting is known for bringing
      researchers and clinicians of the highest caliber together, and this year was no
      exception. 

PMID- 25374969
TI  - A report from the 23rd European Academy of Dermatology and Venereology Congress
      (October 8-12 - Amsterdam, The Netherlands).
AB  - The 23rd Congress of the European Academy of Dermatology and Venereology started
      in Amsterdam with a day dedicated mostly to courses, during which electronic
      posters were also available. Scientists and researchers attending the conference
      had an opportunity for reviewing the latter investigations in dermatology through
      a series of computer terminals showing posters and allowing for e-mail
      discussions with the presenters. In a number of presentations, psoriasis was one
      of the major focuses of interest during EADV. New clinical research with emerging
      biologics and studies to validate the bioequivalence of biosimilars versus their
      originator monoclonal antibodies centered the scientific attractions towards
      which researchers and clinicians attending the conference were drawn. However,
      among the electronic posters at the conference, the results of initial clinical
      trials with a number of potential new therapies for other skin conditions were
      also presented. While shying away from psoriasis, a "late-breaking news in
      dermatology" session, wherein the results of clinical trials with innovative
      therapies for cutaneous diseases were reported, included large trials with
      established drugs aiming at novel indications, as well as first-in-human trials
      to validate the potential of investigational drugs. This and additional
      information and data reported during the conference and related with treatment
      for skin and skin structure diseases are summarized in the following report. 

PMID- 25374970
TI  - A multiplex chemiluminescent biosensor for type B-fumonisins and aflatoxin B1
      quantitative detection in maize flour.
AB  - A multiplex chemiluminescent biosensor for simple, rapid and ultrasensitive on
      site quantification of aflatoxin B1 and type B-fumonisins in maize samples has
      been developed. The biosensor integrates a multiplex indirect competitive lateral
      flow immunoassay (LFIA) based on enzyme-catalyzed chemiluminescence detection and
      a highly sensitive portable charge-coupled device (CCD) camera, employed in a
      lensless "contact" imaging configuration. The developed assay requires a simple
      extraction of the analytes from maize flour samples followed by their detection
      with a 30 min assay time. The use of chemiluminescence detection allowed accurate
      and objective analytes quantification, enabling simultaneous detection of type B
      fumonisins and aflatoxin B1 down to 6 MUg kg(-1) and 1.5 MUg kg(-1),
      respectively, thus fulfilling the standards imposed by the legislation of
      European Union. Maize flour samples spiked with both analytes were subjected to
      multiplex analysis obtaining recoveries ranging from 80 to 115% and the
      coefficient of variation below 20%. Finally, analysis of naturally contaminated
      maize samples resulted in a good agreement between CL-LFIA and a validated
      confirmatory HPLC-UV and commercial ELISA kit, obtaining recoveries in the range
      88-120%. The proposed CL-LFIA protocol is rapid, inexpensive, easy-to-use, and
      fit for the purpose of rapid screening of mycotoxins in maize flour. 

PMID- 25374971
TI  - Towards improved precision in the quantification of surface-enhanced Raman
      scattering (SERS) enhancement factors: a renewed approach.
AB  - This paper demonstrates a renewed procedure for the quantification of surface
      enhanced Raman scattering (SERS) enhancement factors with improved precision. The
      principle of this method relies on deducting the resonance Raman scattering (RRS)
      contribution from surface-enhanced resonance Raman scattering (SERRS) to end up
      with the surface enhancement (SERS) effect alone. We employed 1,8,15,22
      tetraaminophthalocyanato-cobalt(II) (4alpha-Co(II)TAPc), a resonance Raman- and
      electrochemically redox-active chromophore, as a probe molecule for RRS and SERRS
      experiments. The number of 4alpha-Co(II)TAPc molecules contributing to RRS and
      SERRS phenomena on plasmon inactive glassy carbon (GC) and plasmon active GC/Au
      surfaces, respectively, has been precisely estimated by cyclic voltammetry
      experiments. Furthermore, the SERS substrate enhancement factor (SSEF) quantified
      by our approach is compared with the traditionally employed methods. We also
      demonstrate that the present approach of SSEF quantification can be applied for
      any kind of different SERS substrates by choosing an appropriate laser line and
      probe molecule.

PMID- 25374972
TI  - Marta Moita.

PMID- 25374974
TI  - Proceedings of the International Conference on Road Safety (RSS2013),
      International Conference on Road Safety, June 2014, Rome, Italy.

PMID- 25374973
TI  - Silver linings for patients with depression?
AB  - Depression has become one of the biggest health problems globally, but in certain
      places more than in others, suggesting cultural as well as biological causes.
      Neuroscientists are only beginning to understand underlying processes and to
      develop effective treatments for those cases where conventional psychotherapy and
      drugs fail.

PMID- 25374975
TI  - Proceedings of the 94th Annual Meeting of the American Association for Thoracic
      Surgery, April 26-30, 2014, Toronto, Canada.

PMID- 25374976
TI  - Special issue in honor of Britton Chance 100th Commemorative.

PMID- 25374977
TI  - Henrik Kehlet, M.D., Ph.D., recipient of the 2014 Excellence in Research Award.

PMID- 25374978
TI  - Rebecca A. Aslakson, M.D., Ph.D., recipient of the 2014 Presidential Scholar
      Award.

PMID- 25374979
TI  - Proceedings of the 24th International Conference on Genome Informatics (GIW2013),
      December 16-18, 2013, Singapore, Singapore.

PMID- 25374980
TI  - Proceedings from the Texas Tuberculosis Symposium 2013: Strengthening of TB
      research in the border state, April 5, 2013, San Antonio, Texas.

PMID- 25374981
TI  - Festschrift in honor of Robert C. Waag.

PMID- 25374982
TI  - Special section in honor of Robert P. Lisak.

PMID- 25374984
TI  - Proceedings of the 13th International Palynological Congress (XIII IPC) and the
      9th International Organisation of Palaeobotany Conference (IX IOPC), August 23
      30, 2012, Tokyo, Japan.

PMID- 25374983
TI  - Clinically relevant concepts of haemostasis and detection   of coagulopathy after
      trauma and surgery.

PMID- 25374985
TI  - Proceedings of the North American Society of Head and Neck Pathology Companion
      Meeting, March 2, 2014, San Diego, California.

PMID- 25374986
TI  - Introduction to special issue in honor of Professor Povl Krogsgaard-Larsen.

PMID- 25374987
TI  - A practical guide to concentrated insulin for pharmacists.
AB  - PURPOSE: Insulin improves glycemic control in several ways, for example, by
      stimulating glucose uptake in the muscle and inhibiting hepatic glucose
      production. It has other mechanisms of action for correcting the abnormal
      metabolism of proteins, fats, and carbohydrates. The formulation of concentrated
      insulin (U-500) is a higher potency of insulin than the U-100 regular
      formulation. It is indicated for children and adults with type 1 and type 2
      diabetes who have not achieved adequate glycemic control with exercise and proper
      dietary habits. However, the unique characteristics of concentrated insulin
      require that a patient be educated on its use. This article provides a practical
      guide for pharmacists on the use of concentrated insulin in both inpatient and
      outpatient settings and highlights specific concerns and management strategies.
      CONCLUSION: Concentrated insulin works in the same mechanism as U-100 insulin
      formulations for treating type 1 and type 2 diabetes. Pharmacists are
      knowledgeable about managing the disease and can identify patients who will
      benefit with treatment of concentrated insulin. They can provide recommendations
      to prevent and resolve situations, such as dosing errors, which arise in patients
      on concentrated insulin and can educate patients and health care professionals on
      dosing conversions and titration.

PMID- 25374988
TI  - Safety and efficacy of corticosteroid use in neurologic trauma.
AB  - Neurologic trauma, which consists of acute spinal cord injury and traumatic brain
      injury, is a leading cause of death and disability. In recent years, there have
      been improvements in the early recognition and prompt resuscitation of patients
      with neurologic trauma. However, there remain few pharmacologic treatments to
      reduce its secondary complications. Corticosteroids have been used in patients
      with neurologic trauma for more than 5 decades. Traditionally, their use has been
      to improve motor and sensory recovery. However, recently their utility to prevent
      and manage trauma-related pneumonia has been investigated. Given these new
      investigations, the purpose of this review article is to provide a comprehensive
      overview of the history and available scientific evidence surrounding the use of
      corticosteroids in neurologic trauma and caution against the use of these agents
      to prevent hospital-acquired pneumonia in this patient population.

PMID- 25374989
TI  - Azithromycin and the risk of cardiovascular complications.
AB  - The purpose of this review was to evaluate the literature to assess the incidence
      and true clinical relevance of recent Food and Drug Administration warnings
      regarding QT prolongation with azithromycin, given its widespread use, with over
      40 million US outpatient prescriptions written in 2011. A literature search of
      MEDLINE (1946 to May 2013) and International Pharmaceutical Abstracts (1970 to
      May 2013) was conducted using the terms azithromycin, QT prolongation, torsades
      de pointes, arrhythmia, and cardiovascular death. A bibliographic search was also
      performed. Several relevant studies and case reports were identified and
      reviewed. One cohort study revealed an increased risk of cardiovascular death
      with azithromycin compared to no antibiotic, especially in those with higher
      cardiovascular risk. Another cohort study comparing azithromycin, penicillin V,
      and no antibiotic in a younger Danish population with less cardiac risk found no
      increased cardiovascular death associated with azithromycin use. The majority of
      case reports involved ill and/or elderly patients with multiple comorbidities and
      concomitant medications who were already at a higher risk of cardiovascular
      events. Although there is evidence that azithromycin may induce QT prolongation
      and adverse cardiac events, the incidence is fairly limited to patients with high
      baseline risk, including those with preexisting cardiovascular conditions and
      concomitant use of other QT-prolonging drugs.

PMID- 25374990
TI  - Reply to Rodgers: does myostatin induce insulin resistance?

PMID- 25374991
TI  - Response.

PMID- 25374992
TI  - Author's reply.

PMID- 25374993
TI  - Author's reply.

PMID- 25374994
TI  - Author's reply.

PMID- 25374995
TI  - Author's reply.

PMID- 25374996
TI  - Author's reply.

PMID- 25374997
TI  - Author's reply.

PMID- 25374998
TI  - The place of transplantation in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is an uncommon non-Hodgkin lymphoma with a
      heterogeneous natural history. Significant strides have been made in the
      management of MCL. Clinical follow-up exceeds a decade with long-term remission
      durations in some patients. Modern induction strategies employ rituximab; a
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like backbone;
      and cytarabine (in alternating or sequential regimens). However,
      bendamustine/rituximab therapy is challenging these induction strategies. The
      role of transplant is in clinical evolution. Up-front high-dose therapy and
      autologous stem cell transplant remains an attractive option for those with
      chemosensitive disease regardless of the induction regimen chosen, whereas this
      approach in the relapsed or refractory setting has not yielded long-term disease
      free intervals. Reduced-intensity allogeneic stem cell transplant remains a
      viable option in those with relapsed or refractory MCL.

PMID- 25374999
TI  - Novel therapies in mantle cell lymphoma: a pathway to chemotherapy-free
      strategies.
AB  - Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma that has
      been associated with a poor prognosis. Despite improvements in frontline
      management strategies, including the incorporation of cytarabine, intensification
      of chemotherapeutic regimens, and consolidation with transplant, MCL remains
      incurable. Our current understanding of MCL biology affords the opportunity to
      investigate novel, molecularly targeted therapeutic approaches. This review will
      focus on innovative drug development for the treatment of relapsed or refractory
      MCL, including therapies aimed at disrupting the B-cell receptor signaling
      pathway, regulators of apoptosis, and immunomodulators.

PMID- 25375000
TI  - The current clinical value of the DCIS Score.
AB  - The management of ductal carcinoma in situ (DCIS) can be controversial.
      Widespread adoption of mammographic screening has made DCIS a more frequent
      diagnosis, and increasingly smaller, lower-grade lesions are being detected. DCIS
      is commonly treated with breast-conserving surgery and radiation. However, there
      is greater recognition that acceptable cancer control outcomes can be achieved
      for some patients with breast-conserving surgery alone, with radiotherapy
      reserved for those at higher risk of in-breast recurrence. The primary clinical
      dilemma is that there are currently no reliable clinicopathologic features that
      accurately predict which patients will have a recurrence, but risk stratification
      is an area of active research. Molecular profiling has the potential to assess
      recurrence risk based on the individual patient's tumor biology and guide
      treatment decisions. The DCIS Score is a 12-gene assay intended to support
      personalized treatment planning for patients with DCIS following local excision.
      It provides information on local failure risk independent of traditional
      clinicopathologic features. Our group of expert breast surgeons and radiation
      oncologists met in December 2013 at the San Antonio Breast Cancer Symposium to
      discuss current controversies in DCIS management and determine the potential
      value of the DCIS Score in managing these situations. We concluded that the DCIS
      Score provides clinically relevant information about personal risk that can guide
      patient discussions and facilitate shared decision making.

PMID- 25375001
TI  - Information for patients. Advanced prostate cancer.

PMID- 25375002
TI  - What's in a number?

PMID- 25375003
TI  - Current treatment options for non-small-cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) remains a difficult-to-treat malignancy, and
      durable long-term survival is elusive for patients with advanced-stage disease.
      Chemotherapy, especially with platinum-based combinations, is the mainstay of
      treatment, yet these regimens yield only modest response and survival rates.
      Outcomes of recent clinical trials have shown that histology, mutation analyses,
      and biomarkers have an impact on the selection and combination of
      chemotherapeutic agents. Oral tyrosine kinase inhibitors and monoclonal
      antibodies are now part of the treatment schema. Other changes to the treatment
      paradigm include the duration of treatment and the use of maintenance therapy.
      Additionally, chemotherapy is now employed in earlier-stage disease in
      neoadjuvant, adjuvant, and combined-modality treatments. The aim of this article
      is to review the current systemic treatments for NSCLC.

PMID- 25375004
TI  - Evolving and expanding treatment options in NSCLC.

PMID- 25375005
TI  - Contemporary issues in NSCLC.

PMID- 25375006
TI  - A patient with tumor lysis syndrome.
AB  - When caring for a patient with TLS, astute nursing care is required for positive
      patient outcomes. Assessments and monitoring are required for prompt management
      of complications and patient safety. Because of the skilled nursing care that Mr.
      B received, along with supportive medications and hydration, his renal function
      improved, with increased urine output, normalization of electrolytes, and return
      of his appetite.

PMID- 25375007
TI  - Falls in older adults with cancer: a call to action.

PMID- 25375008
TI  - Clinical hypnosis for the palliative care of cancer patients.

PMID- 25375009
TI  - Vismodegib, a hedgehog pathway inhibitor for adults with locally advanced or
      metastatic basal cell carcinoma.

PMID- 25375011
TI  - New report on tackling health inequalities.

PMID- 25375010
TI  - Understanding mammography.

PMID- 25375012
TI  - Association for Nutrition introduces new ethical standards for nutrition.

PMID- 25375013
TI  - Lowering premature deaths from non-communicable diseases.

PMID- 25375014
TI  - Eradication of polio in India.

PMID- 25375015
TI  - Food safety management in the global food supply chain.

PMID- 25375020
TI  - Field-based stable isotope analysis of carbon dioxide by mid-infrared laser
      spectroscopy for carbon capture and storage monitoring.
AB  - A newly developed isotope ratio laser spectrometer for CO2 analyses has been
      tested during a tracer experiment at the Ketzin pilot site (northern Germany) for
      CO2 storage. For the experiment, 500 tons of CO2 from a natural CO2 reservoir was
      injected in supercritical state into the reservoir. The carbon stable isotope
      value (delta(13)C) of injected CO2 was significantly different from background
      values. In order to observe the breakthrough of the isotope tracer continuously,
      the new instruments were connected to a stainless steel riser tube that was
      installed in an observation well. The laser instrument is based on tunable laser
      direct absorption in the mid-infrared. The instrument recorded a continuous 10
      day carbon stable isotope data set with 30 min resolution directly on-site in a
      field-based laboratory container during a tracer experiment. To test the
      instruments performance and accuracy the monitoring campaign was accompanied by
      daily CO2 sampling for laboratory analyses with isotope ratio mass spectrometry
      (IRMS). The carbon stable isotope ratios measured by conventional IRMS technique
      and by the new mid-infrared laser spectrometer agree remarkably well within
      analytical precision. This proves the capability of the new mid-infrared direct
      absorption technique to measure high precision and accurate real-time stable
      isotope data directly in the field. The laser spectroscopy data revealed for the
      first time a prior to this experiment unknown, intensive dynamic with fast
      changing delta(13)C values. The arrival pattern of the tracer suggest that the
      observed fluctuations were probably caused by migration along separate and
      distinct preferential flow paths between injection well and observation well. The
      short-term variances as observed in this study might have been missed during
      previous works that applied laboratory-based IRMS analysis. The new technique
      could contribute to a better tracing of the migration of the underground CO2
      plume and help to ensure the long-term integrity of the reservoir. 

PMID- 25375022
TI  - Conserved atomic bonding sequences and strain organization of graphene grain
      boundaries.
AB  - The bulk properties of polycrystalline materials are directly influenced by the
      atomic structure at the grain boundaries that join neighboring crystallites. In
      this work, we show that graphene grain boundaries are comprised of structural
      building blocks of conserved atomic bonding sequences using aberration corrected
      high-resolution transmission electron microscopy. These sequences appear as
      stretches of identically arranged periodic or aperiodic regions of dislocations.
      Atomic scale strain and lattice rotation of these interfaces is derived by
      mapping the exact positions of every carbon atom at the boundary with ultrahigh
      precision. Strain fields are organized into local tensile and compressive dipoles
      in both periodic and aperiodic dislocation regions. Using molecular dynamics
      tension simulations, we find that experimental grain boundary structures maintain
      strengths that are comparable to idealized periodic boundaries despite the
      presence of local aperiodic dislocation sequences. 

PMID- 25375021
TI  - Estrogen-mediated regulation of mitochondrial gene expression.
AB  - Estrogens, in particular 17beta-estradiol, are well-known regulators of essential
      cellular functions; however, discrepancies remain over the mechanisms by which
      they act on mitochondria. Here we propose a novel mechanism for the direct
      regulation of mitochondrial gene expression by estrogen under metabolic stress.
      We show that in serum-depleted medium, estrogen stimulates a rapid relocation of
      estrogen receptor-alpha to mitochondria, in which it elicits a cellular response,
      resulting in an increase in mitochondrial RNA abundance. Mitochondrial RNA levels
      are regulated through the association of estrogen receptor-alpha with 17beta
      hydroxysteroid dehydrogenase 10, a multifunctional protein involved in steroid
      metabolism that is also a core subunit of the mitochondrial ribonuclease P
      complex responsible for the cleavage of mitochondrial polycistronic transcripts.
      Processing of mitochondrial transcripts affects mitochondrial gene expression by
      controlling the levels of mature RNAs available for translation. This work
      provides the first mechanism linking RNA processing and estrogen activation in
      mitochondrial gene expression and underscores the coordinated response between
      the nucleus and mitochondria in response to stress. 

PMID- 25375023
TI  - Probing interactions between beta-glucan and bile salts at atomic detail by 1H
      13C NMR assays.
AB  - Polysaccharides are prospective hosts for the delivery and sequestration of
      bioactive guest molecules. Polysaccharides of dietary fiber, specifically cereal
      (1 -> 3)(1 -> 4)-beta-glucans, play a role in lowering the blood plasma
      cholesterol level in humans. Direct host-guest interactions between beta-glucans
      and conjugated bile salts are among the possible molecular mechanisms explaining
      the hypocholesterolemic effects of beta-glucans. The present study shows that
      (1)H-(13)C NMR assays on a time scale of minutes detect minute signal changes in
      both bile salts and beta-glucans, thus indicating dynamic interactions between
      bile salts and beta-glucans. Experiments are consistent with stronger
      interactions at pH 5.3 than at pH 6.5 in this in vitro assay. The changes in bile
      salt and beta-glucan signals suggest a stabilization of bile salt micelles and
      concomitant conformational changes in beta-glucans. 

PMID- 25375024
TI  - The association of breastfeeding initiation with sensitivity, cognitive
      stimulation, and efficacy among young mothers: a propensity score matching
      approach.
AB  - OBJECTIVE: This study examined the association between breastfeeding initiation
      and maternal sensitivity, efficacy, and cognitive stimulation among young, low
      income, African American mothers. SUBJECTS AND METHODS: Two hundred twenty-one
      mothers were interviewed during pregnancy, at birth, and at 4 months postpartum
      regarding breastfeeding and parenting. Medical records were collected after
      birth, and mother-infant interactions were videotaped at 4 months. Propensity
      score matching was used to address selection bias by matching breastfeeding and
      nonbreastfeeding mothers on characteristics measured prior to breastfeeding.
      RESULTS: One hundred twenty-four (56%) mothers initiated breastfeeding. After
      matching, mothers who initiated breastfeeding reported greater parenting efficacy
      (effect size, d=0.44) and were observed to be more sensitive with their 4-month
      old infants (effect size, d=0.42) than nonbreastfeeding mothers. Breastfeeding
      was marginally associated with less maternal intrusiveness (effect size, d=0.28)
      but was not related to parenting attitudes or cognitive stimulation. CONCLUSIONS:
      This study presents evidence supporting the claim that breastfeeding may enhance
      maternal efficacy and sensitivity. Providing breastfeeding support to young
      mothers may have effects that extend beyond maternal and child health outcomes to
      parenting and mother-child interactions.

PMID- 25375025
TI  - Development and validation of the comprehensive health activities scale: a new
      approach to health literacy measurement.
AB  - Current health literacy measures have been criticized for solely measuring
      reading and numeracy skills when a broader set of skills is necessary for making
      informed health decisions, especially when information is often conveyed verbally
      and through multimedia video. The authors devised 9 health tasks and a
      corresponding 190-item assessment to more comprehensively measure health literacy
      skills. A sample of 826 participants between the ages of 55 and 74 years who were
      recruited from an academic general internal medicine practice and three federally
      qualified health centers in Chicago, Illinois, completed the assessment. Items
      were reduced using hierarchical factor analysis and item response theory
      resulting in the 45-item Comprehensive Health Activities Scale. All 45 items
      loaded on 1 general latent trait, and the resulting scale demonstrated high
      reliability and strong construct validity using measures of health literacy and
      global cognitive functioning. The predictive validity of the Comprehensive Health
      Activities Scale using self-reported general, physical, and mental health status
      was comparable to or better than widely used measures of health literacy,
      depending on the outcome. Despite comprehensively measuring health literacy
      skills, items in the Comprehensive Health Activities Scale supported 1 primary
      construct. With similar psychometric properties, current measures may be
      adequate, depending on the purpose of the assessment. 

PMID- 25375026
TI  - Structures and bioactivities of dihydrochalcones from Metrodorea stipularis.
AB  - Metrodorea stipularis stem extracts were studied in the search for possible
      antichagastic, antimalarial, and antitumoral compounds using cruzain from
      Trypanosoma cruzi, Plasmodium falciparum, and cathepsins B and L, as molecular
      targets, respectively. Dihydrochalcones 1, 2, 3, and 4 showed significant
      inhibitory activity against all the targets. Compounds 1-4 displayed IC50 values
      ranging from 7.7 to 21.6 MUM against cruzain; dihydrochalcones 2 and 4 inhibited
      the growth of three different strains of P. falciparum in low micromolar
      concentrations; and against cathepsins B and L these compounds presented good
      inhibitory activity with IC50 values ranging from 1.0 to 14.9 MUM. The
      dihydrochalcones showed good selectivity in their inhibitory activities against
      the cysteine proteases. 

PMID- 25375027
TI  - Hypervalent iodine reagent mediated diamination of [60]fullerene with sulfamides
      or phosphoryl diamides.
AB  - A hypervalent iodine-promoted intermolecular diamination reactions of C60 with
      sulfamides or phosphoryl diamides affords two classes of novel C60-fused cyclic
      sulfamide or phosphoryl diamide derivatives. The reaction between C60 and
      sulfamides can be effectively controlled to selectively synthesize diamination
      products or azafulleroids under PhIO/I2 or PhI(OAc)2/I2 conditions, respectively.
      Moreover, phosphoryl diamides were first used as an amine source in the
      diamination of alkenes. 

PMID- 25375028
TI  - Functional analysis of challenging behavior in people with severe intellectual
      disabilities.
AB  - Challenging behaviors exhibited by individuals with developmental disabilities
      often hinder the acquisition of academic, social, and life skills. Functional
      analysis has been useful for assessing challenging behavior in various settings.
      The purpose of this study was to implement an operant methodology for recognizing
      the functional properties of challenging behavior in people with intellectual
      disabilities. Four adults diagnosed with profound intellectual disability
      received assessment under several experimental conditions using a functional
      analysis methodology: social attention as positive reinforcement, negative
      reinforcement such as the termination of demands, positive tangible
      reinforcements, absence of social contingencies, and escape from noisy stimuli.
      Results showed that different types of reinforcement or avoiding contingencies
      affected the rate of aggression, self-injury, disruption, stereotypy, or socially
      offensive behaviors, and functional analysis may potentially be a viable
      alternative for identifying challenging behaviors.

PMID- 25375029
TI  - Pterygodermatites (Paucipectines) baiomydis n. sp. (Nematoda: Rictulariidae), a
      parasite of Baiomys taylori (Cricetidae).
AB  - Pterygodermatites (Paucipectines) baiomydis n. sp., an intestinal parasite of the
      northern pygmy mouse, Baiomys taylori (Cricetidae), collected in La Yerbabuena,
      Colima, Mexico, is described herein. Specimens were studied using light and
      scanning electronic microscopy. This is the 19th species of the subgenus
      Paucipectines described worldwide and the fourth collected in Mexico. It is
      differentiated from the remaining species in the subgenus by having 25 perioral
      denticles, arranged in a triangle (seven on each lateroventral margin, and eleven
      on the dorsal margin), and 10 pairs of caudal papillae. 

PMID- 25375032
TI  - Comparison of COSMED'S FitMateTM and K4b2 metabolic systems reliability during
      graded cycling exercise.
AB  - This study compared the reliability of the Cosmed FitMateTM and K4b2 metabolic
      systems during light to heavy steady state exercise. Expired gas, ventilation
      were recorded in 50 subjects, using in a random order among four sessions, either
      the FitMateTM or the Cosmed K4b2. No differences in oxygen consumption were
      observed between the two systems whatever the intensity. Intraclass correlation
      were high for both analyzers (respectively for the FitMateTM system and the
      Cosmed K4b2; ICC: 0.76-0.88 vs. 0.88-0.95). The FitMateTM metabolic system could
      be a useful reliable and easy-to-use metabolic system in energy expenditure
      measurement.

PMID- 25375034
TI  - AGEs-RAGE system down-regulates Sirt1 through the ubiquitin-proteasome pathway to
      promote FN and TGF-beta1 expression in male rat glomerular mesangial cells.
AB  - We previously demonstrated that advanced glycation-end products (AGEs) promote
      the pathological progression of diabetic nephropathy by decreasing silent
      information regulator 2-related protein 1 (Sirt1) expression in glomerular
      mesangial cells (GMCs). Here, we investigated whether AGEs-receptor for AGEs
      (RAGE) system down-regulated Sirt1 expression through ubiquitin-proteasome
      pathway and whether Sirt1 ubiquitination affected fibronectin (FN) and TGF-beta1,
      2 fibrotic indicators in GMCs. Sirt1 was polyubiquitinated and subsequently
      degraded by proteasome. AGEs increased Sirt1 ubiquitination and proteasome
      mediated degradation, shortened Sirt1 half-life, and promoted FN and TGF-beta1
      expression. Ubiquitin-specific protease 22 (USP22) reduced Sirt1 ubiquitination
      and degradation and decreased FN and TGF-beta1 expression in GMCs under both
      basal and AGEs-treated conditions. USP22 depletion enhanced Sirt1 degradation and
      displayed combined effects with AGEs to further promote FN and TGF-beta1
      expression. RAGE functioned crucial mediating roles in these processes via its C
      terminal cytosolic domain. Inhibiting Sirt1 by EX-527 substantially suppressed
      the down-regulation of FN and TGF-beta1 resulting from USP22 overexpression under
      both normal and AGEs-treated conditions, eventually leading to their up
      regulation in GMCs. These results indicated that the AGEs-RAGE system increased
      the ubiquitination and subsequent proteasome-mediated degradation of Sirt1 by
      reducing USP22 level, and AGEs-RAGE-USP22-Sirt1 formed a cascade pathway that
      regulated FN and TGF-beta1 level, which participated in the pathological
      progression of diabetic nephropathy.

PMID- 25375035
TI  - Mitochondria-associated membrane formation in hormone-stimulated Leydig cell
      steroidogenesis: role of ATAD3.
AB  - Leydig cell steroidogenesis is a multistep process that takes place in the
      mitochondria and endoplasmic reticulum (ER). The physical association between
      these 2 organelles could facilitate both steroidogenesis substrate availability
      and mitochondrial product passage to steroidogenic enzymes in the ER, thus
      regulating the rate of steroid formation. Confocal microscopy, using antisera
      against organelle-specific antigens, and electron microscopy studies demonstrated
      that there is an increase in the number of mitochondria-ER contact sites in
      response to hormone treatment in MA-10 mouse tumor Leydig cells. Electron
      tomography and 3-dimensional reconstruction allowed for the visualization of
      mitochondria-associated membranes (MAMs). MAMs were isolated and found to contain
      the 67-kDa long isoform of the adenosine triphosphatase (ATPase) family, AAA
      domain-containing protein 3 (ATAD3). The 67-kDa ATAD3 is anchored in the inner
      mitochondrial membrane and is enriched in outer-inner mitochondrial membrane
      contact sites. ATAD3-depleted MA-10 cells showed reduced production of steroids
      in response to human choriogonadotropin but not to 22R-hydroxycholesterol
      treatment, indicating a role of ATAD3 in the delivery of the substrate
      cholesterol into the mitochondria. The N terminus of ATAD3 contains 50 amino
      acids that have been proposed to insert into the outer mitochondrial membrane and
      associated organelles such as the ER. Deletion of the ATAD3 N terminus resulted
      in the reduction of hormone-stimulated progesterone biosynthesis, suggesting a
      role of ATAD3 in mitochondria-ER contact site formation. Taken together, these
      results demonstrate that the hormone-induced, ATAD3-mediated, MAM formation
      participates in the optimal transfer of cholesterol from the ER into mitochondria
      for steroidogenesis.

PMID- 25375036
TI  - Anogenital distance plasticity in adulthood: implications for its use as a
      biomarker of fetal androgen action.
AB  - Androgen action during the fetal masculinization programming window (MPW)
      determines the maximum potential for growth of androgen-dependent organs (eg,
      seminal vesicles, prostate, penis, and perineum) and is reflected in anogenital
      distance (AGD). As such, determining AGD in postnatal life has potential as a
      lifelong easily accessible biomarker of overall androgen action during the MPW.
      However, whether the perineum remains androgen responsive in adulthood and thus
      responds plastically to perturbed androgen drive remains unexplored. To determine
      this, we treated adult male rats with either the antiandrogen flutamide or the
      estrogen diethylstilbestrol (DES) for 5 weeks, followed by a 4-week washout
      period of no treatment. We determined AGD and its correlate anogenital index
      (AGI) (AGD relative to body weight) at weekly intervals across this period and
      compared these with normal adult rats (male and female), castrated male rats, and
      appropriate vehicle controls. These data showed that, in addition to reducing
      circulating testosterone and seminal vesicle weight, castration significantly
      reduced AGD (by ~17%), demonstrating that there is a degree of plasticity in AGD
      in adulthood. Flutamide treatment increased circulating testosterone yet also
      reduced seminal vesicle weight due to local antagonism of androgen receptor.
      Despite this suppression, surprisingly, flutamide treatment had no effect on AGD
      at any time point. In contrast, although DES treatment suppressed circulating
      testosterone and reduced seminal vesicle weight, it also induced a significant
      reduction in AGD (by ~11%), which returned to normal 1 week after cessation of
      DES treatment. We conclude that AGD in adult rats exhibits a degree of
      plasticity, which may be mediated by modulation of local androgen/estrogen
      action. The implications of these findings regarding the use of AGD as a lifelong
      clinical biomarker of fetal androgen action are discussed.

PMID- 25375037
TI  - TLR4 expression in bone marrow-derived cells is both necessary and sufficient to
      produce the insulin resistance phenotype in diet-induced obesity.
AB  - The anomalous activation of toll-like receptor 4 (TLR4) by dietary fats is one of
      the most important mechanisms linking obesity to insulin resistance. TLR4 is
      expressed in most tissues of the body, but its activity in the cells of the
      immune system is expected to underlie its most important roles of inducing
      inflammation and insulin resistance. Here we explore the hypothesis that TLR4
      expression in bone marrow-derived cells mediates most of the actions of this
      receptor as an inducer of insulin resistance. Wild type and TLR4-mutant mice were
      used in bone marrow transplant experiments producing chimeras that harbored the
      functional receptor in all cells of the body except bone marrow-derived cells or
      only in bone marrow-derived cells. Transplanted mice were fed chow or a high-fat
      diet, and glucose homeostasis was evaluated by glucose and insulin tolerance
      tests. Insulin signal transduction and the expression of markers of inflammation
      were evaluated in the liver and white adipose tissue. In addition, we performed
      liver histology and evaluated the expression of gluconeogenic enzymes. The
      expression of TLR4 in bone marrow-derived cells only, but not in non-bone marrow
      derived tissues only, was a determining factor in the induction of diet-induced
      insulin resistance, which was accompanied by an increased expression of
      inflammatory markers in both white adipose tissue and liver as well as increased
      liver steatosis and increased expression of gluconeogenic enzymes. TLR4 expressed
      in bone marrow-derived cells is an important mediator of obesity-associated
      insulin resistance in mice.

PMID- 25375040
TI  - Isomer dependence in the assembly and lability of silver(I)
      trifluoromethanesulfonate complexes of the heteroditopic ligands, 2-, 3-, and 4
      [di(1H-pyrazolyl)methyl]phenyl(di-p-tolyl)phosphine.
AB  - Three isomers of a new heteroditopic ligand that contains a di(1H
      pyrazolyl)methyl (-CHpz2) moiety connected to a di(p-tolyl)phosphine group via a
      para-, meta-, or ortho-phenylene spacer (pL, mL, and oL, respectively) have been
      synthesized by using a palladium(0)-catalyzed coupling reaction between HP(p
      tolyl)2 and the appropriate isomer of (IC6H4)CHpz2. The 1:1 complexes of
      silver(I) trifluoromethanesulfonate, Ag(OTf), were prepared to examine the nature
      of ligand coordination and the type of supramolecular isomer (monomeric, cyclic
      oligomeric, or polymeric) that would be obtained. The single crystal X-ray
      diffraction studies showed that [Ag(pL)](OTf), 1, and [Ag(mL)](OTf), 2, possessed
      cyclic dimeric dications, whereas [Ag(oL)](OTf), 3, was a coordination polymer.
      The polymeric chain in 3 could be disrupted by reaction with triphenylphosphine,
      and the resulting complex, [Ag(oL)(PPh3)](OTf), 4, possessed a monometallic
      cation where the ligand was bound to silver in a chelating kappa(2)P,N-
      coordination mode. The solution structures of 1-4 were probed via a combination
      of IR, variable-temperature multinuclear ((1)H, (13)C, (31)P) NMR spectroscopy,
      as well as by electron spray ionization (ESI)(+) mass spectrometry. A related
      complex [Ag(m-IC6H4CHpz2)2](OTf), 5, was also prepared, and its solid-state and
      solution spectroscopic properties were studied for comparison purposes. These
      studies suggest that the cyclic structures of 1 and 2 are likely preserved but
      are dynamic in solution at room temperature. Moreover, both 3 and 4 have dynamic
      solution structures where 3 is likely extensively dissociated in CH3CN or acetone
      rather than being polymeric as in the solid state. 

PMID- 25375038
TI  - ErbB receptor-driven prolactinomas respond to targeted lapatinib treatment in
      female transgenic mice.
AB  - As ErbB receptors are expressed in prolactinomas and exhibit downstream effects
      on prolactin (PRL) production and cell proliferation, we generated transgenic
      mice using a PRL enhancer/promoter expression system to restrict lactotroph
      specific expression of human epidermal growth factor receptor (EGFR) or human
      EGFR2 (HER2). EGFR or HER2 transgenic mice developed prolactinomas between 13 and
      15 months, and confocal immunofluorescence and Western blot analysis confirmed
      lactotroph-restricted PRL and EGFR or HER2 coexpression. Circulating PRL levels
      in EGFR and HER2 transgenic mice were increased 5- and 3.8-fold, respectively.
      Inhibiting EGFR or HER2 signaling with oral lapatinib (100 mg/kg), a dual
      tyrosine kinase inhibitor for both EGFR and HER2, suppressed circulating PRL by
      72% and attenuated tumor PRL expression by 80% and also attenuated downstream
      tumor EGFR/HER2 signaling. This model demonstrates the role of ErbB receptors
      underlying prolactinoma tumorigenesis and the feasibility of targeting these
      receptors for translation to treatment of refractory prolactinomas.

PMID- 25375039
TI  - Molecular imaging of folate receptor beta-positive macrophages during acute lung
      inflammation.
AB  - Characterization of markers that identify activated macrophages could advance
      understanding of inflammatory lung diseases and facilitate development of novel
      methodologies for monitoring disease activity. We investigated whether folate
      receptor beta (FRbeta) expression could be used to identify and quantify
      activated macrophages in the lungs during acute inflammation induced by
      Escherichia coli LPS. We found that FRbeta expression was markedly increased in
      lung macrophages at 48 hours after intratracheal LPS. In vivo molecular imaging
      with a fluorescent probe (cyanine 5 polyethylene glycol folate) showed that the
      fluorescence signal over the chest peaked at 48 hours after intratracheal LPS and
      was markedly attenuated after depletion of macrophages. Using flow cytometry, we
      identified the cells responsible for uptake of cyanine 5-conjugated folate as
      FRbeta(+) interstitial macrophages and pulmonary monocytes, which coexpressed
      markers associated with an M1 proinflammatory macrophage phenotype. These
      findings were confirmed using a second model of acute lung inflammation generated
      by inducible transgenic expression of an NF-kappaB activator in airway
      epithelium. Using CC chemokine receptor 2-deficient mice, we found that FRbeta(+)
      macrophage/monocyte recruitment was dependent on the monocyte chemotactic protein
      1/CC chemokine receptor 2 pathway. Together, our results demonstrate that folate
      based molecular imaging can be used as a noninvasive approach to detect
      classically activated monocytes/macrophages recruited to the lungs during acute
      inflammation. 

PMID- 25375041
TI  - Peripheral nerve allografting - why and how?
AB  - The authors briefly present the methods of reconstruction of peripheral nerve
      gaps. Of these methods, the reconstruction with nerve allografts is reviewed
      mainly in what concerns the ways to achieve host tolerance for the allograft. The
      authors underline the fact that, for the recipient it is better to suppress the
      graft antigenicity than to suppress the host immune response. Further, the
      authors present the most important methods to denaturate a nerve allograft in
      order to make it nonantigenic and insist upon developing methods that can be used
      in human beings. The authors conclude that reconstruction of nerve defects with
      peripheral nerve allografts is a very rewarding method that should be extended in
      clinical practice.

PMID- 25375042
TI  - Multidisciplinary management of adult low grade gliomas.
AB  - BACKGROUND: Adult hemispheric low grade gliomas (LGG) cover a pathologic spectrum
      which has specific clinical, histological and molecular characteristics. The
      optimal management of these tumors is still a controversial topic in
      international literature. METHODS: We evaluated scientific papers from the
      literature (Medline and Cochrane Library to date) and we compared the results
      found there with our experience, trying to create a pattern of treatment of our
      own. RESULTS AND CONCLUSIONS: The advances in microsurgical and neuromonitoring
      techniques, as well as in neuroimaging, allow for a more aggressive resection of
      LGG with a significant improvement in overall survival and quality of life. The
      potential risks of the "wait and see" policy and the neurotoxicity of
      radiotherapy are challenged by the benefits of careful surgical resection and up
      front chemotherapy. The present day treatment strategy, based on recent evidence,
      should include a maximal surgical resection when possible, with the full
      preservation of the patients ability, and delayed radiotherapy. The role of
      temozolomide in the management of LGG and the identification of the therapeutic
      modality with the best quality of life profile will be determined by ongoing
      trials. The further characterization of prognostic relevance of molecular markers
      and data from advanced imaging techniques needs an intensification of research
      and validation efforts. ABBREVIATIONS: LGG: low grade gliomas, WHO: World Health
      Organization, OS: overall survival, PFS: progression-free survival, MRI: Magnetic
      resonance imaging, MRS: Magnetic resonance spectroscopy, MPFS: malignant
      progression-free survival, rCBV: Relative Cerebral Blood Volume, QOL: quality of
      life, FLAIR: Fluid attenuated inversion recovery, MGMT: O6-methylguanine DNA
      methyltransferase enzyme, DSC MR imaging: Dynamic Susceptibility Contrast
      Perfusion MR imaging, 1H-MRS: Proton Magnetic Resonance Spectroscopy, IDH1:
      isocitrate dehydrogenase 1 gene, SPECT: Single-photon emission computed
      tomography, PET: Positron emission tomography, DTI-FT: Diffuse Tensor Imaging
      fiber tracking technique, DES: direct electrical stimulation, EEG:
      Electroencephalography, EcoG: Electrocorticography, MEP: motor evoked potentials,
      EMG: Electromyography, AED: anti-epileptic drugs, TMZ: Temozolomide, EORTC:
      European Organization for Research and Treatment of Cancer, NCCTG: North Central
      Cancer Treatment Group, RTOG: Radiation Therapy Oncology Group, ECOG: Eastern
      Cooperative Oncology Group, EOR: extent of resection, Gy: Gray (unit), GyE: gray
      equivalent, RT: radiation therapy, IMRT: image-guided intensity modulated
      radiotherapy, FSRT: fractionated stereotactic radiotherapy, SRS: proton therapy
      or stereotactic radiosurgery, LET: high-linear energy transfer beams, RBE:
      relative biological effectiveness, CTCAE: Common Terminology Criteria for Adverse
      Events, PCV: procarbazine, lomustine, and vincristine chemotherapy.

PMID- 25375043
TI  - Esophagectomy in esophageal cancer - is there an optimal approach?
AB  - INTRODUCTION: Esophageal cancer is a public health problem,with increasing
      incidence and postoperative morbidity over the past recent years. Although a
      number of new surgical techniques, including minimally invasive surgery, have
      been developed, mortality and morbidity have remained elevated.The element that
      seems to influence the early postoperative morbidity and mortality is the method
      of approach. MATERIAL AND METHODS: retrospective observational study which is
      carried out in the period 2003-2012 including esophageal neoplasm patients
      operated in the First Surgical Clinic -Hospital "Sf. Spiridon", Iasi. 140
      patients were included, of which only 33 have received surgery with curative aim.
      SURGICAL TECHNIQUE: we consider 2 techniques in our study:transhiatal (TH)
      technique (without opening the chest)followed by esophagoplasty with cervical
      anastomosis and transthoracic esophagectomy (TT) with intrathoracic or cervical
      anastomosis. RESULTS: We performed 57.58 % (n = 19) of interventions by TT versus
      42.42% (n = 14) by TH. The overall rate of postoperative morbidity rate was 78.8%
      (n = 26). Overall early postoperative mortality rate was 15.5% (n = 5) caused by
      pleuropulmonary sepsis (2 cases), lung emboli (1 case) and sepsis caused by
      anastomotic leak (2 cases). CONCLUSION: TT and TH esophagectomy have precise
      indications in esophageal surgery for malignancies, the mortality and morbidity
      rate being strongly influenced by the surgical approach.

PMID- 25375044
TI  - Laparoscopic treatment in achalasia of the cardia.
AB  - BACKGROUND: Achalasia, although a rare disease (an incidence of 1 100 000
      individuals each year) is one of the common causes of motor dysphagia and is
      characterized by loss of peristalsis in the esophageal body and lack of
      relaxation of the lower esophageal sphincter. AIM: The aim of our study was to
      perform a clinical,therapeutic and evolution evaluation in patients diagnosed
      with achalasia and operated in our department between 1997 and 2013. MATERIAL AND
      METHODS: We performed a retrospective study using the clinical charts, operatory
      protocols, imagistic and video database of the 17 patients with achalasia
      operated in our department. RESULTS: We encountered an equal repartition in women
      and men and a predominance of urban provenience. Ages were between 24 and 86
      years (with an average age of 51). There were two cases of recurrent achalasia at
      2, respectively 5 years after the first operation. In all cases, Heller myotomy
      was used, with the addition of a Dor fundoplication in 12 cases and Toupet
      fundoplication in five cases, as an antireflux procedure. Mean operation time was
      117.6 minutes.There were three iatrogenic perforations of the esophageal mucosa,
      all of them recognized and treated in the same operative time. No postoperative
      complications related to the Heller-Dor Heller-Toupet procedure were
      encountered.The follow-up was between 3 and 72 months. CONCLUSIONS: Laparoscopic
      approach in the treatment of achalasia provides the advantages of minimally
      invasive surgery, but also and very important, a good visualization of the
      abdominal esophagus and gastroesophageal junction.Heller esocardiomyotomy is
      usually associated with anantireflux procedure. A Dor fundoplication is generally
      used,although the Toupet fundoplication may also be used with the same
      advantages. It is important to monitor these patients on a yearly basis, knowing
      the risk of dysplasia carcinoma in achalasia.

PMID- 25375045
TI  - Total thyroidectomy with LigaSure Small Jaw versus conventional thyroidectomy - a
      clinical study.
AB  - INTRODUCTION: The emergence of LigaSure device in surgical practice brings some
      real benefits in thyroid surgery. UsingLigaSure Small Jaw device in total
      thyroidectomy is an important step in thyroid surgery. The aim of this study is
      to present the initial experience of Surgical Clinic I of Targu Mures staff in
      terms of total thyroidectomy using this procedure, without ligatures compared to
      the conventional technique with ligatures. MATERIAL AND METHOD: The study
      included 20 consecutive patients (19 females and one male) who have undergone
      total thyroidectomy in Surgical Clinic I of the Emergency County Hospital Targu
      Mures, between September 2012 - February 2013. Group I included 10 patients who
      underwent total thyroidectomty using the LigaSure Small Jaw device (without
      ligatures) while the second group included 10 patients in whom total
      thyroidectomy was performed by classical procedure (using vascular ligatures).
      The two groups were compared using statistical analysis following the next
      parameters: the thyroid pathology, operation time, number of hospitalization
      days,analgesia and immediate postoperative complications. RESULTS: This method
      provides a statistically significant decrease of the operative time and
      hospitalization days. CONCLUSION: Using LigaSure Small Jaw device in thyroid
      surgery is a safe procedure with little complications rate.

PMID- 25375046
TI  - Hemithyroidectomy for unilateral thyroid disease.
AB  - AIM: To identify rates of recurrence and hypothyroidism after hemithyroidectomy
      for unilateral nodular thyroid diseases and its advantages over bilateral radical
      resections. METHODS: Fifty patients who underwent thyroid lobectomy with
      unilateral thyroid disease were included. Follow-up with thyroid function tests
      on the first month and then once every three months, as well as ultrasonography
      controls once a year were performed postoperatively. Recurrence, which was
      accepted asat least one nodule with a diameter of 5 mm on the remnant lobe, and
      the need for postoperative thyroxin therapy were analysed, along with the
      relation of both with preoperative medical therapy, histological results, numbers
      and diameters of thyroid nodules, follow-up duration. RESULTS: The incidence of
      recurrent disease after hemithyroidectomy was 12% after a mean follow-up time of
      25.2 months (range, 10-43) while the incidence of clinical hypothyroidism which
      needs thyroxin therapy was 8%. Gender, age,substitutive and suppressive therapy
      before operation,histological evaluation, the presence of multiple nodules and
      diameter of nodules were predictive of neither recurrence nor post operative
      thyroxin therapy. CONCLUSION: Hemithyroidectomy for unilateral thyroid disease
      has a moderate rate of recurrence, low rates of hypothyroidism and rare
      postoperative complications, with short hospital stay.

PMID- 25375047
TI  - The use of Ligasure vessel sealing system in axillary dissection; effect on
      seroma formation.
AB  - BACKGROUND: Seroma formation is the most frequent postoperative complication
      after axillary dissection for breast surgery with an incidence of 10 - 50 %. This
      prospective clinical randomized study was carried out to evaluate the Ligasure
      vessel sealing system and its effect on seromaformation and other complications
      for axillary dissection. METHODS: Between January 2006 and November 2007, the
      patients with histopathological diagnosis of breast cancer were analysed
      prospectively. The patients with positive sentinel lymph node biopsy or clinical
      axillary involvement were included in the study, and the patients who underwent
      neoadjuvant therapy or using anticoagulants have been excluded from the study.
      Patients were divided into two study groups.Axillary dissection was performed in
      the first group by LigaSure and in the second group by linking and
      electrocautery. RESULTS: There were a total of thirty three patients with a mean
      age of 51.4 +- 13.7. In group one, mean age of patients was 54.1 +- 13.2 and
      48.68 +- 14.1 in group two. There was no significant statistical difference
      between the groups regarding age, body mass index, excised tissue weight,tumour
      size and number of excised lymph nodes. The use of Ligasure reduced drainage
      amount and duration of drain till removal, but increased operative time.
      CONCLUSION: There were no significant differences between study groups regarding
      the complications. LigaSure electrothermal bipolar vessel sealing system can be
      safely used in axillary dissection as an alternative to traditional methods.

PMID- 25375048
TI  - GSTM1, GSTT1 and GSTP1 in patients with multiple breast cancers and breast cancer
      in association with another type of cancer.
AB  - INTRODUCTION: breast cancer has the highest incidence in women.Glutathione S
      transferases (GSTs) are a large group of enzymes involved in the metabolism of
      xenobiotics. The members of this gene superfamily are involved in the development
      of multiple cancers. OBJECTIVES: the aim of the study was to see whether the
      GSTM1, GSTT1 and GSTP1 genetic polymorphisms are risk factors for patients
      diagnosed with multiple malignancies, of which at least one is located in the
      breast. MATERIALS AND METHODS: in the period between 2005 and 2012,of the 520
      patients diagnosed with breast cancer, 69 had multiple primitive malignant
      tumors, of which at least one was localized in the breast. The research on GSTM1,
      GSTT1 and GSTP1 genotypes consisted of 59 patients diagnosed with multiple breast
      cancers or with breast cancer in association with another type of cancer,
      compared with a group of healthy controls. RESULTS: in the subgroup of patients
      with breast cancer in association with another type of cancer, the GSTM1 null
      genotype was present in 61.2% of patients, compared to 29% of controls; the
      subgroup of metachronous breast cancers, the presence of any of the GSTT1 or
      GSTM1 null genotypes was statistically significantly different from that of
      controls (65.2%vs. 28.5%); in the subgroup with synchronous cancers, the GSTM1
      null genotype was found in 66.6% of patients compared to 9% for the controls, and
      the presence of any null genotype (GSTM1 and GSTT1) was also statistically
      significant in the case group. CONCLUSIONS: the GSTM1 null genotype is a risk
      factor for synchronous breast cancers and for breast cancer associated with
      extramammary cancer; the presence of null genotypes(GSTM1 or GSTT1) is a risk
      factor for multiple breast cancer(bilateral or synchronous); the GSTT1 null
      genotype and the heterozygous variant allele (Ile105Val) and homozygous variant
      allele (Val105Val) of GSTP1 are not risk factors for the cases studied.

PMID- 25375049
TI  - Is surgical treatment of liver hemangiomas effective for pain relief?
AB  - BACKGROUND: Traditional treatment for liver hemangiomas is surgery. Currently, it
      is controversial whether hemangioma surgeries are sufficiently beneficial for the
      patients. In this study, we evaluated the effectiveness of surgery in patients
      with liver hemangiomas. METHODS: Forty-two patients who underwent surgical
      operations for hepatic hemangiomas were retrospectively evaluated and
      interviewed. RESULTS: Study population included 36 female and 6 male patients
      whose ages ranged between 26 and 65 years (mean age, 47.8 +-8.7 years). Their
      mean duration of hospitalization was 6 days (range, 3 - 59 days). The median time
      since surgery was 50 months (range 0-120 months). There was a statistically
      significant decrease in numerical rating and adjective rating pain scale scores
      (p 0.05). Postoperatively, pain did not cease in 10 patients (peptic ulcers
      requiring medical treatment in four patients, cholelithiasis in four patients,
      and nephrolithiasis in two patients). CONCLUSION: Patients with cavernous
      hemangiomas of the liver who require surgical treatment have significant benefits
      in terms of pain relief following surgery. The lack of pain relief after the
      surgery in some patients may be related to concomitant medical problems other
      than the hemangioma.

PMID- 25375050
TI  - Changes in the operating time of laparoscopic cholecystectomy of the surgeons and
      novices between 1994-2012.
AB  - BACKGROUND: The technique of laparoscopic cholecystectomy(LC) has not changed
      over the past recent years; therefore the possibility is open to study its
      learning curve. METHODS: Retrospectively, every third year's LCs were analysed
      between 1994 and 2012. The learning curves of surgeons and novices were defined
      in the department. The surgeons have scored the laparoscopic technique of their
      colleagues on a scale of 1 to 10 and operation time (OT) was examined in light of
      the assistant's technique. RESULTS: 2,216 LCs were performed in the examined
      period.The average OT of the department was 78.3 minutes in 1994,which had
      decreased to 45.4 minutes (42.0%) by 2003. The improvement rates of surgeons and
      novices were 36.7% and respectively 9.9%, and the variance between the minimum
      and maximum OT changed in parallel. The OT in the initial 3 years of learning had
      become 13% shorter by 2006 and the first section of the learning curve has also
      become steeper. In case of surgeons whose technical points were low and OT was
      short, the assistants average technical score was significantly higher than in
      case of surgeons whose technical score was high and the OT was short. CONCLUSION:
      The OT alone is not an objective factor in the definition of the surgical
      technique.

PMID- 25375051
TI  - Anatomo-clinical analysis of 14 consecutive cases of primary cystic mesenterico
      epiploic tumors.
AB  - BACKGROUND: The aim of this study is an anatomo-clinical evaluation of the
      primary cystic mesenterico-epiploic tumors,based on a single-center's 15 year
      experience. MATERIAL AND METHOD: We performed a retrospective study of a series
      of 14 primary cystic mesenterico-epiploic tumors that were operated in the
      Surgical Department 4 UMPh Targu-Mures, Romania, between 01.01.1997 and
      01.01.2012. Data about the clinical complaints, imagistic aspects, associated
      lesions, surgical approach, hospitalization, pathology, and immediate and late
      postoperative course were recorded and analysed using the Microsoft Excel
      software. RESULTS: In all cases we performed a complete and intact surgical
      excision, using an open approach in 13 cases and laparoscopy in 1 case, with no
      mortality and no significant surgical-related morbidity; we have encountered a
      single recurrence at 1.5 years after surgery. We had no preoperative pathological
      diagnosis; the exact preoperative anatomic location of the tumor was possible
      only in one case. Pathologic examination showed the following types: inclusion
      cysts - 4 cases, enteral duplication cysts - 2 cases, simple mesothelialcysts - 6
      cases, cystic lymphangioma - 1 case and simple lymphatic cyst - 1 case. We have
      systematized 3 clinicoimagistic patterns according to the dimension of the
      tumor,with no relationship to the histologic origin of the tumor. CONCLUSIONS:
      Primary cystic mesenterico-epiploic tumors aredifficult to diagnose
      preoperatively. Complete excision is usually possible, even for large tumors.
      These relatively rare tumors must be considered in the differential diagnosis of
      cystic abdominal masses.

PMID- 25375052
TI  - Management of recurrent or metastatic retroperitoneal soft-tissue sarcomas.
AB  - Retroperitoneal soft tissue sarcomas remain a serious therapeutic problem. The
      aim of the study is to define the optimal treatment strategy of patients with
      locally recurrent or metastatic retroperitoneal soft tissue sarcomas. MATERIAL
      AND METHODS: A retrospective study was performed.Between 2001 and 2013, 89
      patients with retroperitoneal soft tissue sarcomas were surgically treated in the
      University Hospital Queen Joanna ISUL and the Specialized Hospital for Active
      Treatment in Oncology Sofia. Clinicopathological data were investigated with SPSS
      19. RESULTS: The mean time of onset of the first and second relapse of sarcomas
      was 23 and 13 months, respectively. Over 40% of the studied patients underwent
      more than one operation because of recurrence. Ability of radical extirpation of
      the tumour decreased with each subsequent relapse. The 5 year survival rate was
      60% for patients with primary combined radical resection versus 28% for patients
      with partial resection. In the presence of metastatic lesions the 3 year survival
      rate was only 22%. CONCLUSION: Local recurrences, the presence of distant
      metastases and the ability of radical extirpation are the main long term
      prognostic factors.

PMID- 25375053
TI  - Laparoscopic surgical treatment of umbilical hernia and small eventrations with
      prosthetic mesh using omentum overlay.
AB  - INTRODUCTION: Umbilical hernias and abdominal incisional hernias represent
      current pathologies which require numerous surgical alternative ways of treatment
      in prosthetic or non prosthetic,open or minimally invasive surgery. The method
      proposed by us is a less expensive option with no additional risks compared to
      other similar procedures as surgical technique. MATERIALS AND METHODS: We
      conducted a retrospective study between 01.01.2008 - 01.06.2013 in which we
      considered a number of 23 patients with umbilical hernia and eventration,
      patients who received laparoscopic intraperitoneal polyester mesh covered with
      omentum, procedure applied at the IInd Surgery Clinic, Clinical County Emergency
      Hospital Sibiu. RESULTS: Out of 23 patients with postoperative umbilical hernia
      and eventration cases in which we used this surgical technique,16 were umbilical
      hernias and 7 post incisional hernias. The average time of surgery was 1 hour and
      40 minutes, recording 4 postoperative complications remitted under conservative
      treatment, with a mean hospitalization of 4.1 days. CONCLUSIONS: Proepiploic
      laparoscopic treatment using omentum is a reliable alternative to a more
      expensive and difficult procedure involving Dual Mesh.

PMID- 25375055
TI  - Progressive preoperative pneumoperitoneum (PPP) as an adjunct for surgery of
      hernias with loss of domain.
AB  - BACKGROUND: forced repair of a giant abdominal wall defect end with
      unsatisfactory results despite development of prosthetics materials. The
      enlargement of abdominal wall dimensions could be realized altogether other
      methods with the aid of pneumo-peritoneum. The aim of the study is to evaluate
      early results of the method used for patients with giant incisional hernias.
      MATERIAL AND METHODS: between june 1998 - june 2013, 17 patients (4 males) with
      giant abdominal wall defects (incisional and inguinal hernias) were prepaired for
      radical surgery with pneumoperitoneum. Average age was 64.35 years. We
      reevaluated the standard constants of the pulmonary function,blood gases, and
      intra-vesical pressure in 3 moments: before the first gas insuflation, 24 hours
      before surgery and in the 7th daypost operatively. RESULTS: the method was free
      of accidents or incidents, no mortality was recorded. The respiratory function
      was significantly increased and also the intra-abdominal pressure. CONCLUSION:
      our results suggest that the method of progressive pneumoperitoneum is safe,
      costless of choice for creating a clear compatibility between the wall and
      abdominal content inpatients with giant abdominal wall defects. Also ensures a
      longterm and stable improvement of the respiratory function in all its
      components.

PMID- 25375054
TI  - Human fibrin glue sealing versus suture polypropylene fixation in Lichtenstein
      inguinal herniorrhaphy: a prospective observational study.
AB  - BACKGROUND: Patients who underwent primary inguinal hernia repair still report a
      high rate of postoperative pain after operation due to the effect of mesh
      fixation by suture.An alternative is the use of human fibrin glue. We compared
      the two techniques. METHODS: 468 patients randomly underwent primary inguinal
      hernia Lichtenstein repair fixing the mesh by suture or by human fibrin glue
      (HFG); in both cases the mesh was fixed to the posterior wall of the inguinal
      canal and to the inguinal ligament. RESULTS: No significant differences were
      recorded between the two groups in terms of complications, while the sutureless
      technique reduces the operative time and the postoperative pain. CONCLUSIONS: A
      widespread technique for the treatment of inguinal hernia is the application of a
      mesh using Lichtenstein procedure. The prosthesis can be fixed by traditional
      suture or using a new method of sutureless fixation with adhesive materials that
      shows an excellent local tolerability and lack of adverse effects and
      contraindications.

PMID- 25375056
TI  - Poststernotomy wound management by debridement and pedicle flaps reconstruction.
AB  - BACKGROUND: Sternal wound infection and sternal dehiscence are very serious,
      sometimes life-threatening complications of cardiac surgery, which require
      immediate attention. The mortality rate can reach 50%. During the past 30
      years,various flaps for coverage of sternal wounds have been described.
      OBJECTIVE: The authors objective was to evaluate their 7-year experience with
      flaps used for coverage of poststernotomy wounds, with an emphasis on flap
      selection and post repair complications. RESULTS: The records of 15 patients were
      reviewed. The most common coverage techniques were pectoralis major flap (n=5)and
      rectus abdominis flap (n=4). Four patients had both of these flaps. One patient
      had a latissimus dorsi flap, and another one had an omental flap. Eight of the 15
      patients experienced a local complication; these included seroma(n=2), hematoma
      (n = 1), infection requiring debridement and antibiotics (n = 2), partial flap
      necrosis (n = 2) and abdominal hernia (n=1). The perioperative mortality rate was
      13.3% (n = 2), and all deaths were attributable to multiple organ deficiency due
      to sepsis. CONCLUSIONS: Early debridement and coverage of the remained defects
      with flaps are the two main principles in the management of poststernotomy
      infected wounds, especially insituations where rapid wound healing and recovery
      are extremely important. Individual approach to each patient and proper selection
      of the method of reconstruction significantly reduces the postoperative morbidity
      and mortality rate.

PMID- 25375057
TI  - Smooth loop arterio-venous fistula.
AB  - The number of patients with End Stage Kidney Disease is continuously growing.
      There still are some difficulties in managing vascular access, creating it and
      dealing with all of its complications. Arterio-venous fistula is the ideal
      procedure increating the vascular access. Our goal is to present a surgical
      technique that we consider to be feasible in creating the brahio-cephalic arterio
      venous fistula: the smooth loop fistula.If anatomically possible we prefer to
      create the barhio-cephalic fistula by using the median-basilica vein continued
      with the median cephalic vein to create a smooth loop between the brachial artery
      and the cephalic vein. By giving this J shape to the anastomosis there will be a
      smoother flow through the fistula, increasing its patency rate.

PMID- 25375058
TI  - Large piece of wood board removal and long term survival in a patient with
      stabbed thoracic wound - case report.
AB  - Stabbed thoracic trauma is quite common in military practice,but they very rarely
      occur in civilian life, where they are predominantly accidental injuries.
      Thoracic stabbed wounds are more commonly observed in men than in women and in
      younger rather than older people. The management and prognosis depend on the
      composition, size and location of the foreign body. A 28-year-old Caucasian woman
      presented to the emergency room with hemorrhagic shock, a large stabbed wound and
      retention of a large piece of wood board.Less than 10 minutes after arriving to
      the emergency room she underwent open surgical thoracotomies and resection of the
      spleen rupture without any significant postoperative complications. At the end of
      the procedure the left breast was reconstructed. The original aspects of this
      case are the singularity of the foreign body and its relative harmlessness in
      spite of its large size.

PMID- 25375059
TI  - Biliary cast - complication of cholangitis and pancreatitis in a pancreas divisum
      patient.
AB  - We report a rare cause of biliary cast secondary to cholangitis and pancreatitis,
      in a 60 year old female patient with pancreas divisum. She was admitted in our
      hospital with an acute pancreatitis (alcoholic etiology was excluded) complicated
      with pancreatic abscess and obstructive jaundice. The patient had undergone a
      complex surgical intervention: cholecystectomy,choledocotomy with extraction of
      the biliary thrombus,external biliary drainage through a T tube, evacuation of
      the pancreatic abscess, sequestrectomy, peritoneal lavage and multipledrainages.
      In spite of the surgical and intensive care support,the biliary drainage through
      the T tube had ceased and the obstructive jaundice had reappeared in a more
      accentuated fashion. Endoscopic retrograde cholangiography showed complete
      pancreas divisum and diffuse multiple stenosis alternating with dilatation of the
      intrahepatic biliary tree (a pattern of sclerosing cholangitis). An endoscopic
      prosthesis was placed inside the right hepatic bile duct. Despite the use of the
      combined endoscopic plus UDCA (ursodeoxycholic acid) treatment for the management
      of the biliary cast syndrome, the evolution was unfavorable with hepatic
      coma,septic shock and finally death. The necropsy revealed an extensive biliary
      cast in the entire biliary tree and pyogeniccholangitis. The patient had a fatal
      outcome despite all the surgical, endoscopic and conservative efforts, with
      development of intraductal biliary obstruction and secondary pyogenic
      cholangitis. Biliary cast syndrome is a rare but very aggressive entity and its
      management is often difficult despite the advances in surgery and endoscopy
      treatments.

PMID- 25375060
TI  - Anterior transperitoneal laparoscopic approach of retroperitoneal tumour -
      clinical case.
AB  - We present our personal experience in the anterior transperitoneal laparoscopic
      approach of a retroperitoneal tumour.The case we have in view is that of a 48
      year old female patient P.V., with congenital single left kidney. The patient has
      a retroperitoneal tumour mass of the right flank. Following investigations
      (ultrasound, CT with contrast), the tumour appeared well defined, of small
      dimensions (approximately 6-7cm diameter) and without anatomical relationships
      with large retroperitoneal vessels (inferior vena cava). For the laparoscopic
      excision of the tumour, we used an operating device adapted from the one used in
      right hemi-colectomy. After the coloparietal dissection, the access into the
      right retroperitoneal flank by means of laparoscopy is achieved by applying our
      procedure.The surgical intervention was quick and of a minimally invasive nature.
      Postoperative evolution was favourable, without any complications; the patient
      was discharged after 48 hours. In anatomic situations where the tumour anatomy is
      well defined and its size is acceptable, without dangerous anatomic relationships
      with large retroperitoneal vessels, attempted laparoscopic transperitoneal
      removal is the preferred option.

PMID- 25375061
TI  - Peristomal necrotizing fasciitis - peculiar evolution of a patient with
      metachronous colonic tumors.
AB  - We hereby present a case report of a patient with an unusual neoplasic and
      surgical history. M.V. is a 54-year-old patient who had been operated, two years
      ago, for intestinal obstruction caused by a sigmoid tumor; a segmental rectal and
      sigmoid resection (Hartmann's procedure) was then performed. Two other surgical
      procedures were attempted during the last two years, in another surgical
      department: a colo-rectal anastomosis and a repair of the parastomal hernia, both
      failed due to postoperative adhesions syndrome. The patient was hospitalized for
      peristomal gangrene with necrotizing fasciitis. Emergency action was taken to
      resolve the parietal gangrene. The postoperative local evolution of the wound was
      favourable and allowed a skin graft for parietal restoration. An intestinal
      obstruction occurred 2 months later, caused by an extended metachronous tumor of
      the splenic flexure. The patient underwent other surgeries including the
      completion of the left hemicolectomy, total gastrectomy, caudal
      splenopancreatectomy and left adrenalectomy. The patient has a favourable
      postoperative evolution after 1 year. CONCLUSION: We noticed a very severe
      evolution of the peristomal gangrene and the rapid growth towards intestinal
      obstruction of the metachronous colonic tumor.

PMID- 25375062
TI  - Abdominal wall non-clostridian gas cellulitis: a rare complication of a
      colostoma.
AB  - The authors report the case of a 69 year-old patient, with obesity, having a left
      colostomy that has been made for rectal cancer (12 years ago) and who developed a
      non-clostridian gascellulitis of the abdominal wall as a result of intraparietal
      traumatic tract perforation of the colostomy. The presence of the peristomal
      hernia favoured the posttraumatic injury of the colostomy. Repeated surgical
      inteventions and the antibiotic treatment determined a favourable evolution.
      Despite the wound contamination with excrement, transit stoma relocation was not
      necessary. Some clinical and therapeutic aspects of abdominal wall infections are
      presented.

PMID- 25375063
TI  - Difficulties in the diagnostics and treatment of near-total congenital megacolon.
AB  - Near total colonic aganglionosis is one of the rarest forms of Hirschsprung's
      disease and until recent years it has been considered deadly. Establishing a
      correct diagnosis has proven to be challenging, because while the clinical and
      radiological features can be useful, they are not pathognomonic. Chronic
      intestinal obstruction and long-term parenteral nutrition dependency are
      associated with a high mortality risk for these patients. While there is no
      current consensus with regards to a superior operative method, the patients
      benefit from surgical techniques aimed at lengthening the intestine, as well as
      from intestine transplant. We report the case of a newborn baby girl who was
      admitted to our clinic for abdominal distension,biliary and fecaloid vomiting.
      With an initial suspicion of digestive tract malformation, the diagnosis of near
      total congenital megacolon was established with great difficulty and the infant
      underwent serial surgeries, ending up with an extended myotomy-myectomy
      (Ziegler's procedure) as a curative approach, with favorable immediate
      postoperative evolution.However, the patient developed sepsis and although the
      infection was treated accordingly, the baby's general condition kept
      deteriorating and exitus was recorded 77 days after admission.

PMID- 25375064
TI  - The legacy of Prof. Constantin Arseni. The medical architect behind the Romanian
      School of Neurosurgery.
AB  - The personality of Prof. Dr. Constantin Arseni (1912-1994) is without any doubt a
      key point in any discussion regarding the history of the Romanian School of
      Neurosurgery. Now at two decades since the regretted passing-away of Prof. Arseni
      the authors present several pieces of data regarding the early beginnings of
      neurosurgery in Romania and how this discipline has evolved over time in our
      country. Driven by an incredible tenacity Professor Constantin Arseni managed not
      only to create the first completely independent clinic of neurosurgery in
      Romania, but also to keep it continuously updated with the latest bibliographic
      and technological resources available at the time. Professor Arseni's
      masterpiece, the largest neurosurgical hospital in Europe (at the time of its
      construction)was supposed to be a completely autonomous institute dedicated to
      surgery on the human central nervous system. As the Iron Curtain fell and Europe
      was marked by continuous reforms, the idea of an institute dedicated to the brain
      was abandoned by the authorities and a multidisciplinary hospital dedicated to
      neurosurgical emergencies and trauma was born.

PMID- 25375065
TI  - Health promotion and primary health care: examining the discourse.
AB  - The health promotion discourse is comprised of assumptions about health and
      health care that are compatible with primary health care. An examination of the
      health promotion discourse illustrates how assumptions of health can help to
      inform primary health care. Despite health promotion being a good fit for primary
      health care, this analysis demonstrates that the scope in which it is being
      implemented in primary health care settings is limited. The health promotion
      discourse appears largely compatible with primary health care-in theory and in
      the health care practices that follow. The aim of this article is to contribute
      to the advancement of theoretical understanding of the health promotion
      discourse, and the relevance of health promotion to primary health care. 

PMID- 25375068
TI  - Analysis and modeling of heat-labile enterotoxins of Escherichia coli suggests a
      novel space with insights into receptor preference.
AB  - Features of heat-labile enterotoxins of Escherichia coli which make them fit to
      use as novel receptors for antidiarrheals are not completely explored. Data-set
      of 14 different serovars of enterotoxigenic Escherichia coli producing heat
      labile toxins were taken from NCBI Genbank database and used in the study.
      Sequence analysis showed mutations in different subunits and also at their
      interface residues. As these toxins lack crystallography structures, homology
      modeling using Modeller 9.11 led to the structural approximation for the E. coli
      producing heat-labile toxins. Interaction of modeled toxin subunits with
      proanthocyanidin, an antidiarrheal showed several strong hydrogen bonding
      interactions at the cost of minimized energy. The hits were subsequently
      characterized by molecular dynamics simulation studies to monitor their binding
      stabilities. This study looks into novel space where the ligand can choose the
      receptor preference not as a whole but as an individual subunit. Mutation at
      interface residues and interaction among subunits along with the binding of
      ligand to individual subunits would help to design a non-toxic labile toxin and
      also to improve the therapeutics. 

PMID- 25375069
TI  - Premature deaths among children with epilepsy - South Carolina, 2000-2011.
AB  - Epilepsy is a common childhood neurologic disorder. In 2007, epilepsy affected an
      estimated 450,000 children aged 0-17 years in the United States. Approximately
      53% of children with epilepsy and special health care needs have co-occurring
      conditions, and only about one third have access to comprehensive care. The few
      studies of mortality risk among children with epilepsy as compared with the
      general population generally find a higher risk for death among children with
      epilepsy with co-occurring conditions but a similar risk for death among children
      with epilepsy with no co-occurring conditions. However, samples from these
      mortality studies are often small, limiting comparisons, and are not
      representative. This highlights the need for expanded mortality surveillance
      among children with epilepsy to better understand their excess mortality. This
      report describes mortality among children with epilepsy in South Carolina during
      2000-2011 by demographic characteristics and underlying causes of death. The
      overall mortality rate among children with epilepsy was 8.8 deaths per 1,000
      person-years, and the annual risk for death was 0.84%. Developmental conditions,
      cardiovascular disorders, and injuries were the most common causes of death among
      children with epilepsy. Team-based care coordination across medical and
      nonmedical systems can improve outcomes and reduce health care costs for children
      with special health care needs, but they require more study among children with
      epilepsy. Ensuring appropriate and timely health care and social services for
      children with epilepsy, especially those with complications, might reduce the
      risk for premature death. Health care providers, social service providers,
      advocacy groups and others can work together to assess whether coordinated care
      can improve outcomes for children with epilepsy. 

PMID- 25375070
TI  - Declines in pneumonia hospitalizations of children aged <2 years associated with
      the use of pneumococcal conjugate vaccines - Tennessee, 1998-2012.
AB  - The 7-valent pneumococcal conjugate vaccine (PCV7) was added to the U.S. infant
      immunization schedule in the year 2000. By 2009, PCV7 introduction was associated
      with a 43% decline in all-cause pneumonia among U.S. children aged <2 years. In
      2010, a new 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the
      infant immunization schedule, expanding protection from seven to 13 pneumococcal
      serotypes. To examine changes in all-cause pneumonia hospitalizations among
      children aged <2 years after the switch to PCV13, Tennessee hospital discharge
      data for 1998-2012 were analyzed. By 2012, all-cause pneumonia hospitalizations
      in children aged <2 years had declined an additional 27%, relative to the PCV7
      years. Pneumonia hospitalizations were estimated to be 4.1 per 1,000 population
      in 2012, a historically low rate that represents a 72% decline from the rate
      before PCV7 introduction. Tennessee children aged <2 years experienced about
      1,300 fewer pneumonia hospitalizations annually in 2011 and 2012 than in the
      years before pneumococcal conjugate vaccine (PCV) use. These data attest to the
      powerful impact of the PCV program on pneumonia in Tennessee children. The
      observed trend likely represents a major decline in pneumococcal pneumonia, which
      should stimulate a reassessment of current causes and appropriate management of
      pneumonia in children. 

PMID- 25375071
TI  - Arthritis among veterans - United States, 2011-2013.
AB  - Arthritis is among the most common chronic conditions among veterans and is more
      prevalent among veterans than nonveterans. Contemporary population-based
      estimates of arthritis prevalence among veterans are needed because previous
      population-based studies predate the Persian Gulf War, were small, or studied men
      only despite the fact that women comprise an increasing proportion of military
      personnel and typically have a higher prevalence of arthritis than men. To
      address this knowledge gap, CDC analyzed combined 2011, 2012, and 2013 Behavioral
      Risk Factor Surveillance System (BRFSS) data among all adults aged >=18 years, by
      veteran status, to estimate the total and sex-specific prevalence of doctor
      diagnosed arthritis overall and by sociodemographic categories, and the state
      specific prevalence (overall and sex-specific) of doctor-diagnosed arthritis.
      This report summarizes the results of these analyses, which found that one in
      four veterans reported that they had arthritis (25.6%) and that prevalence was
      higher among veterans than nonveterans across most sociodemographic categories,
      including sex (prevalence among male and female veterans was 25.0% and 31.3%,
      respectively). State-specific, age-standardized arthritis prevalence among
      veterans ranged from 18.8% in Hawaii to 32.7% in West Virginia. Veterans comprise
      a large and important target group for reducing the growing burden of arthritis.
      Those interested in veterans' health can help to improve the quality of life of
      veterans by ensuring that they have access to affordable, evidence-based,
      physical activity and self-management education classes that reduce the adverse
      effects of arthritis (e.g., pain and depression) and its common comorbidities
      (e.g., heart disease and diabetes). 

PMID- 25375072
TI  - Vital signs: cervical cancer incidence, mortality, and screening - United States,
      2007-2012.
AB  - BACKGROUND: Cervical cancer screening is one of the greatest cancer prevention
      achievements, yet some women still develop or die from this disease. OBJECTIVE:
      To assess recent trends in cervical cancer incidence and mortality, current
      screening percentages, and factors associated with higher incidence and death
      rates and inadequate screening. METHODS: Percentages of women who had not been
      screened for cervical cancer in the past 5 years were estimated using data from
      the 2012 Behavioral Risk Factor Surveillance System survey. State-specific
      cervical cancer incidence data from the United States Cancer Statistics and
      mortality data from the National Vital Statistics System were used to calculate
      incidence and death rates for 2011 by state. Incidence and death rates and annual
      percentage changes from 2007 to 2011 were calculated by state and U.S. Census
      region. RESULTS: In 2012, the percentage of women who had not been screened for
      cervical cancer in the past 5 years was estimated to be 11.4%; the percentage was
      larger for women without health insurance (23.1%) and for those without a regular
      health care provider (25.5%). From 2007 to 2011, the cervical cancer incidence
      rate decreased by 1.9% per year while the death rate remained stable. The South
      had the highest incidence rate (8.5 per 100,000), death rate (2.7 per 100,000),
      and percentage of women who had not been screened in the past 5 years (12.3%).
      CONCLUSIONS: Trends in cervical cancer incidence rates have decreased slightly
      while death rates have been stable over the last 5 years. The proportion of
      inadequately screened women is higher among older women, Asians/Pacific
      Islanders, and American Indians/Alaska Natives. IMPLICATIONS FOR PUBLIC HEALTH
      PRACTICE: There continue to be women who are not screened as recommended, and
      women who die from this preventable cancer. Evidence-based public health
      approaches are available to increase women's access to screening and timely
      follow-up of abnormal results.

PMID- 25375073
TI  - Establishment of a community care center for isolation and management of Ebola
      patients - Bomi County, Liberia, October 2014.
AB  - As of October 29, 2014, a total of 6,454 Ebola virus disease (Ebola) cases had
      been reported in Liberia by the Liberian Ministry of Health and Social Welfare,
      with 2,609 deaths. Although the national strategy for combating the ongoing Ebola
      epidemic calls for construction of Ebola treatment units (ETUs) in all 15
      counties of Liberia, only a limited number are operational, and most of these are
      within Montserrado County. ETUs are intended to improve medical care delivery to
      persons whose illnesses meet Ebola case definitions, while also allowing for the
      safe isolation of patients to break chains of transmission in the community.
      Until additional ETUs are constructed, the Ministry of Health and Social Welfare
      is supporting development of community care centers (CCCs) for isolation of
      patients who are awaiting Ebola diagnostic test results and for provision of
      basic care (e.g., oral rehydration salts solutions) to patients confirmed to have
      Ebola who are awaiting transfer to ETUs. CCCs often have less bed capacity than
      ETUs and are frequently placed in areas not served by ETUs; if built rapidly
      enough and in sufficient quantity, CCCs will allow Ebola-related health measures
      to reach a larger proportion of the population. Staffing requirements for CCCs
      are frequently lower than for ETUs because CCCs are often designed such that
      basic patient needs such as food are provided for by friends and family of
      patients rather than by CCC staff. (It is customary in Liberia for friends and
      family to provide food for hospitalized patients.) Creation of CCCs in Liberia
      has been led by county health officials and nongovernmental organizations, and
      this local, community-based approach is intended to destigmatize Ebola, to
      encourage persons with illness to seek care rather than remain at home, and to
      facilitate contact tracing of exposed family members. This report describes one
      Liberian county's approach to establishing a CCC. 

PMID- 25375074
TI  - Notes from the field: severe environmental contamination and elevated blood lead
      levels among children - Zambia, 2014.
AB  - Lead poisoning can have devastating health consequences, especially for children,
      with childhood lead exposure estimated to contribute to 600,000 new cases
      globally of children with intellectual disabilities every year. Lead exposure is
      entirely preventable, yet is estimated to account for 0.6% of the global burden
      of disease, with the highest burden in developing regions. Kabwe, the second
      largest city in Zambia with a population of approximately 203,000, is located in
      Zambia's Copperbelt. During 1904-1994, lead mining and smelting operations
      contaminated the soil in residential areas, but no extensive environmental health
      assessment was completed. In 2003, the World Bank funded the Copperbelt
      Environmental Project to assist the Government of Zambia in addressing
      environmental health problems related to the mining sector. Components of the
      project included removal of mining waste materials, soil remediation, resident
      evacuation, and treatment of lead-exposed children. During July 22-28, 2014, a
      team from PureEarth/Blacksmith Institute, the City University of New York School
      of Public Health, and Green Cross Switzerland conducted extensive surface soil
      testing and blood lead testing of children in six communities adjacent to the now
      closed Kabwe mines and smelters. 

PMID- 25375075
TI  - Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle
      symptoms: a randomized clinical study.
AB  - BACKGROUND: Statin use is frequently associated with muscle-related symptoms.
      Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin
      myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease
      statin-associated muscular pain in a specific group of patients with mild-to
      moderate muscle symptoms. MATERIAL/METHODS: Fifty patients treated with statins
      and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme
      Q10 supplementation over a period of 30 days (50 mg twice daily), and the control
      group (n=25) received placebo. The Brief Pain Inventory (BPI) questionnaire was
      used and blood testing was performed at inclusion in the study and after 30 days
      of supplementation. RESULTS: The intensity of muscle pain, measured as the Pain
      Severity Score (PSS), in the Q10 group was reduced from 3.9+/-0.4 to 2.9+/-0.4
      (P<0.001). The Pain Interference Score (PIS) after Q10 supplementation was
      reduced from 4.0+/-0.4 to 2.6+/-0.4 (P<0.001). In the placebo group, PSS and PIS
      did not change. Coenzyme Q10 supplementation decreased statin-related muscle
      symptoms in 75% of patients. The relative values of PSS and PIS significantly
      decreased (-33.1% and -40.3%, respectively) in the Q10 group compared to placebo
      group (both P<0.05). From baseline, no differences in liver and muscle enzymes or
      cholesterol values were found. CONCLUSIONS: The present results show that
      coenzyme Q10 supplementation (50 mg twice daily) effectively reduced statin
      related mild-to-moderate muscular symptoms, causing lower interference of statin
      related muscular symptoms with daily activities.

PMID- 25375076
TI  - Reversible and rapid pH-regulated self-assembly of a poly(ethylene glycol)
      peptide bioconjugate.
AB  - The use of external triggers to manipulate the secondary structure of self
      assembling peptides conjugated to flexible synthetic polymers is a challenging
      problem, particularly in terms of reversibility. Here, we demonstrate, for the
      first time, sustained rapid and reversible, pH-regulated self-assembly of the
      peptide ELELELELELF (EL-5F) and its conjugates with 2 and 5 kDa poly(ethylene
      glycol) (EL-5F-PEG-2K and EL-5F-PEG-5K). Circular dichroism indicated the
      formation of beta-sheet structures at pH < 5.9, 5.8, and 5.4 and disassembly to
      random coils above those pH values for EL-5F, EL-5F-PEG-2K, and EL-5F-PEG-5K,
      respectively. beta-sheets were confirmed by the thioflavin T assay, while
      transmission electron microscopy revealed the existence of extended fibrillar
      structures below the above pH values. pH-induced secondary structure conversion
      was reproducible for over 15 cycles, even at salt concentrations of up to 200 mM
      NaCl, and was quantitatively related to the pH. Self-supporting hydrogelation
      after self-assembly was observed at concentrations as low as 0.2 wt %, which is
      15-fold lower than previously reported concentrations. This simple approach to
      mediate reversible self-assembly of EL-5F-PEG bioconjugates is expected to offer
      novel functionality relevant to drug delivery and bioseparation systems. 

PMID- 25375077
TI  - ACOs and the future of medicine: an interview with Morey Menacker, DO.

PMID- 25375078
TI  - Perspectives on healthcare from the 2014 Edward J. 3rd Excellence in Medicine
      honorees.

PMID- 25375079
TI  - Hospital readmissions and the potential impact on medicare reimbursement.

PMID- 25375080
TI  - Legislative brief: New Jersey legislative update.

PMID- 25375081
TI  - Shifting the focus: from illness to wellness & prevention: a five-year plan to
      reduce chronic disease.

PMID- 25375082
TI  - Ethical & legal considerations for physician orders for life-sustaining
      treatment.

PMID- 25375083
TI  - Hospice: the physician's role in supporting quality care near the end of life.

PMID- 25375084
TI  - Caring for the woman, not the whipple.

PMID- 25375085
TI  - Protocolized versus non-protocolized weaning for reducing the duration of
      mechanical ventilation in critically ill adult patients.
AB  - BACKGROUND: This is an update of a review last published in Issue 5, 2010, of The
      Cochrane Library. Reducing weaning time is desirable in minimizing potential
      complications from mechanical ventilation. Standardized weaning protocols are
      purported to reduce time spent on mechanical ventilation. However, evidence
      supporting their use in clinical practice is inconsistent. OBJECTIVES: The first
      objective of this review was to compare the total duration of mechanical
      ventilation of critically ill adults who were weaned using protocols versus usual
      (non-protocolized) practice.The second objective was to ascertain differences
      between protocolized and non-protocolized weaning in outcomes measuring weaning
      duration, harm (adverse events) and resource use (intensive care unit (ICU) and
      hospital length of stay, cost).The third objective was to explore, using subgroup
      analyses, variations in outcomes by type of ICU, type of protocol and approach to
      delivering the protocol (professional-led or computer-driven). SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library Issue 1, 2014), MEDLINE (1950 to January 2014), EMBASE (1988 to
      January 2014), CINAHL (1937 to January 2014), LILACS (1982 to January 2014),  ISI
      Web of Science and ISI Conference Proceedings (1970 to February 2014), and
      reference lists of articles. We did not apply language restrictions. The original
      search was performed in January 2010 and updated in January 2014. SELECTION
      CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs of
      protocolized weaning versus non-protocolized weaning from mechanical ventilation
      in critically ill adults. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted data. We performed a priori subgroup and
      sensitivity analyses. We contacted study authors for additional information. MAIN
      RESULTS: We included 17 trials (with 2434 patients) in this updated review. The
      original review included 11 trials. The total geometric mean duration of
      mechanical ventilation in the protocolized weaning group was on average reduced
      by 26% compared with the usual care group (N = 14 trials, 95% confidence interval
      (CI) 13% to 37%, P = 0.0002). Reductions were most likely to occur in medical,
      surgical and mixed ICUs, but not in neurosurgical ICUs. Weaning duration was
      reduced by 70% (N = 8 trials, 95% CI 27% to 88%, P = 0.009); and ICU length of
      stay by 11% (N = 9 trials, 95% CI 3% to 19%, P = 0.01). There was significant
      heterogeneity among studies for total duration of mechanical ventilation (I(2) =
      67%, P < 0.0001) and weaning duration (I(2) = 97%, P < 0.00001), which could not
      be explained by subgroup analyses based on type of unit or type of approach.
      AUTHORS' CONCLUSIONS: There is evidence of reduced duration of mechanical
      ventilation, weaning duration and ICU length of stay with use of standardized
      weaning protocols. Reductions are most likely to occur in medical, surgical and
      mixed ICUs, but not in neurosurgical ICUs. However, significant heterogeneity
      among studies indicates caution in generalizing results. Some study authors
      suggest that organizational context may influence outcomes, however these factors
      were not considered in all included studies and could not be evaluated. Future
      trials should consider an evaluation of the process of intervention delivery to
      distinguish between intervention and implementation effects. There is an
      important need for further development and research in the neurosurgical
      population.

PMID- 25375086
TI  - Fabrication of water-dispersible and highly conductive PSS-doped PANI/graphene
      nanocomposites using a high-molecular weight PSS dopant and their application in
      H2S detection.
AB  - This work describes the fabrication of poly(4-styrenesulfonic acid)-doped
      polyaniline/graphene (PSS-doped PANI/graphene) nanocomposites and their use as
      sensing elements for hydrogen sulfide (H2S) detection. PSS with a weight-average
      molecular weight (Mw) of 1.96 * 10(6) was synthesized using low-temperature free
      radical polymerization. The PSS was used as both a doping agent and a binding
      agent for the polymerization of aniline monomers in a biphasic system (water
      chloroform) at -50  degrees C. The high Mw of PSS resulted in relatively large
      particle sizes and smooth surfaces of the PSS-doped PANI. These physical
      characteristics, in turn, resulted in low interparticle resistance and high
      conductivity. In addition, the PSS allowed homogeneous dispersion of reduced
      graphene sheets through electrostatic repulsion. The prepared PSS-doped
      PANI/graphene solutions showed good compatibility with flexible poly(ethylene
      terephthalate) (PET) substrates, making them suitable for flexible sensor
      electrodes. Changes in the charge-transport properties, such as protonation
      level, conjugation length, crystalline structure, and charge-transfer resistance,
      of the electrode materials were the main factors influencing the electrical and
      sensor performance of the PSS-doped PANI-based electrodes. PSS-doped
      PANI/graphene composites containing 30 wt% graphene showed the highest
      conductivity (168.4 S cm(-1)) and the lowest minimum detection level (MDL) for
      H2S gas (1 ppm). This result is consistent with the observed improvements in
      charge transport in the electrode materials via strong pi-pi stacking
      interactions between the PANI and the graphene sheets. 

PMID- 25375087
TI  - The role of filament length, finite-extensibility and motor force dispersity in
      stress relaxation and buckling mechanisms in non-sarcomeric active gels.
AB  - After relaxing some assumptions we apply a single-chain mean-field mathematical
      model recently introduced [RSC Adv. (2014)] to describe the role of molecular
      motors in the mechanical properties of active gels. The model allows physics that
      are not available in models postulated on coarser levels of description. Moreover
      it proposes a level of description that allows the prediction of observables at
      time scales too difficult to achieve in multi-chain simulations for realistic
      filament lengths and densities. We model the semiflexible filaments that compose
      the active gel as bead-spring chains; molecular motors are accounted for by using
      a mean-field approach, in which filaments undergo transitions of one motor
      attachment state depending on the state of the probe filament. The level of
      description includes the end-to-end distance and attachment state of the
      filaments, and the motor-generated forces, as stochastic state variables which
      evolve according to a proposed differential Chapman-Kolmogorov equation. The
      motor-generated forces are drawn from a stationary distribution of motor stall
      forces. We consider bead-spring chains with multiple beads, explore the effect of
      finite-extensibility of the strands and incorporate into the model motor force
      distributions that have been measured experimentally. The model can no longer be
      solved analytically but is amenable to numerical simulation. This version of the
      model allows a more quantitative description of buckling dynamics [Lenz et. al.
      PRL, 2012, 108, 238107] and the dynamic modulus of active gels. The effect of
      finite extensibility of the filament strands on the dynamic modulus was also
      found to be in agreement with the microrheology experiments of Mizuno et. al.,
      [Science, 2007, 315, 370-373]. 

PMID- 25375088
TI  - Long-term results and prognostic factors of underlay myringoplasty in pars tensa
      atelectasis in children.
AB  - IMPORTANCE: Pars tensa retraction is a frequent condition in chronic otitis
      media, and there is a large diversity of opinions regarding its management.
      OBJECTIVE: To report the long-term results and prognostic factors of
      myringoplasty in pediatric patients with grade 5 pars tensa atelectasis. DESIGN,
      SETTING, AND PARTICIPANTS: This was an observational, retrospective case review,
      conducted at a referral university hospital, of children undergoing surgical
      intervention for dry tympanic disruption after a clinical history of tensa
      retraction with a transcanal or postauricular approach under general anesthesia.
      INTERVENTIONS: Underlay myringoplasty with temporalis fascia or tragal
      perichondrium by transcanal or postauricular approach under general anesthesia.
      MAIN OUTCOMES AND MEASURES: Anatomical results are reported with a minimum follow
      up of 5 years analyzing perforation or retraction of the neotympanum. Age; sex;
      side, position, and size of the eardrum disruption; surgical approach; graft
      material; and presence of contralateral disease were correlated with anatomical
      failure. RESULTS: The population included 33 girls and 28 boys undergoing 65
      interventions; the age varied from 4 to 16 years (mean [SD], 10 [3.2] years). An
      intact tympanic membrane was obtained in 58 cases (89.2%) with a follow-up
      varying from 5 to 14 years (mean follow-up, 9 years). None of the variables
      analyzed significantly predisposed patients to tympanic perforation after
      surgical repair. There were no new progressive retractions. CONCLUSIONS AND
      RELEVANCE: Tensa retraction resulting in a tympanic disruption can be cured by
      underlay myringoplasty with perichondrium or temporalis fascia with results
      similar to those of simple tympanic perforations without recurrent retraction
      even in the long-term period.

PMID- 25375089
TI  - Highly emissive copper(I) complexes bearing diimine and
      bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolane.
AB  - A highly emissive copper(I) complex bearing (4R,5R)-(-)-4,5
      bis(diphenylphosphinomethyl)-2,2-dimethyl-1,3-dioxolane (diop) and 2,9-dimethyl
      4,7-diphenyl-1,10-phenanthroline (dmpp), [Cu(dmpp)(diop)]PF6 (1.PF6), was newly
      synthesized. The quantum yield of the luminescence of 1.PF6 in degassed
      dichloromethane is 0.38, which is one of the highest values among all copper(I)
      complexes bearing two bidentate ligands, diimine and diphosphine, under the same
      conditions. The long lifetime (26 MUs) and high intensity of the emission come
      from the small non-radiative decay rate of the excited states. The TD-DFT study
      indicates that the charge transfer transition from both copper and diphosphine to
      diimine orbitals plays an important role in the photophysical properties.
      Photophysics of [Cu(dmp)(diop)]PF6 (2.PF6, dmp = 2,9-dimethyl-1,10
      phenanthroline) was also studied in order to reveal the effects of the
      introduction of the phenyl group at 4- and 7-positions of phenanthroline.

PMID- 25375090
TI  - MicroRNA-9 promotes tumor metastasis via repressing E-cadherin in esophageal
      squamous cell carcinoma.
AB  - MicroRNAs (miRNAs) play a critical role in development and progression of
      cancers. Deregulation of MicroRNA-9 (miR-9) has been documented in many types of
      cancers but their role in the development of esophageal squamous cell carcinoma
      (ESCC) has not been studied. This study aimed to investigate the effect of miR-9
      in esophageal cancer metastasis. The up-regulation of miR-9 was frequently
      detected in primary ESCC tumor tissue, which was significantly associated with
      clinical progression (P = 0.022), lymph node metastasis (P = 0.007) and poor
      overall survival (P < 0.001). Functional study demonstrated that miR-9 promoted
      cell migration and tumor metastasis, which were effectively inhibited when
      expression of miR-9 was silenced. Moreover, we demonstrated that miR-9 interacted
      with the 3'-untranslated region of E-cadherin and down-regulated its expression,
      which induced beta-catenin nuclear translocation and subsequently up-regulated c
      myc and CD44 expression. In addition, miR-9 induced epithelial-mesenchymal
      transition (EMT) in ESCC, a key event in tumor metastasis. Taken together, our
      study demonstrates that miR-9 plays an important role in ESCC metastasis by
      activating beta-catenin pathway and inducing EMT via targeting E-cadherin. Our
      study also suggests miR-9 can be served as a new independent prognostic marker
      and/or as a novel potential therapeutic target for ESCC. 

PMID- 25375092
TI  - Metformin and salinomycin as the best combination for the eradication of NSCLC
      monolayer cells and their alveospheres (cancer stem cells) irrespective of EGFR,
      KRAS, EML4/ALK and LKB1 status.
AB  - The presence of cancer stem cells (CSCs) is linked to preexisting or acquired
      drug resistance and tumor relapse. Therefore, targeting both differentiated tumor
      cells and CSCs was suggested as an effective approach for non-small cell lung
      cancer (NSCLC) treatment. After screening of chemotherapeutic agents, tyrosine
      kinase inhibitors (TKIs) or monoclonal antibody in combination with the putative
      stem cell killer Salinomycin (SAL), we found Metformin (METF), which modestly
      exerted a growth inhibitory effect on monolayer cells and alveospheres/CSCs of 5
      NSCLC cell lines regardless of their EGFR, KRAS, EML4/ALK and LKB1 status,
      interacted synergistically with SAL to effectively promote cell death. Inhibition
      of EGFR (AKT, ERK1/2) and mTOR (p70 s6k) signaling with the combination of METF
      and SAL can be augmented beyond that achieved using each agent individually.
      Phospho-kinase assay further suggested the multiple roles of this combination in
      reducing oncogenic effects of modules, such as beta-catenin, Src family kinases
      (Src, Lyn, Yes), Chk-2 and FAK. Remarkably, significant reduction of sphere
      formation was seen under combinatorial treatment in all investigated NSCLC cell
      lines. In conclusion, METF in combination with SAL could be a promising treatment
      option for patients with advanced NSCLC irrespective of their EGFR, KRAS,
      EML4/ALK and LKB1 status. 

PMID- 25375091
TI  - MTOR inhibition enhances NVP-AUY922-induced autophagy-mediated KIT degradation
      and cytotoxicity in imatinib-resistant gastrointestinal stromal tumors.
AB  - Our previous study demonstrated NVP-AUY922, a HSP90AA1 inhibitor, could enhance
      mutant KIT degradation in gastrointestinal stromal tumor (GIST) cells through
      both proteasome- and autophagy-mediated pathways. Herein, we showed rapamycin, a
      MTOR inhibitor and autophagy inducer, could reduce total and phospho-KIT
      expression levels and enhance apoptosis in imatinib-resistant GIST cells. The
      involvement of autophagy in rapamycin-induced KIT downregulation was further
      confirmed by co-localization of KIT and autophagosome, and partial recovery of
      KIT expression level by either siRNA-mediated BECN1 and ATG5 silencing or
      autophagy inhibitors after rapamycin. Rapamycin and NVP-AUY922 synergistically
      inhibited GIST cells growth in vitro. The combination of low-dose NVP-AUY922 with
      rapamycin had comparable effects on reducing KIT expression, increasing MAP1LC3B
      puncta and tumor necrosis, and inhibiting tumor growth as high-dose NVP-AUY922
      did in GIST430 xenograft model. Our results suggest the addition of a MTOR
      inhibitor may reduce NVP-AUY922 dose requirement and potentially improve its
      therapeutic index in mutant KIT-expressing GISTs. 

PMID- 25375094
TI  - Aqueous self-assembly of chromophore-conjugated amphiphiles.
AB  - The self-assembly of pi-conjugated building blocks has been a topic of interest
      in last few years owing to their close relevance to optoelectronic device
      applications. If such building blocks are made amphiphilic by appropriate
      derivatization, then the self-assembly can be realized in water by the strong
      hydrophobic repulsive forces between the polar medium and the rigid pi-surface.
      On the other hand, as pi-pi interactions are directional, such self-assembly can
      produce structurally precise nano-structures, compared to classical surfactants.
      With these objectives, the self-assembly of several amphiphilic pi-systems has
      been studied in the recent past and is described in this article. Examples
      include electron-deficient, electron-rich and also mixed assemblies of donor and
      acceptor type chromophores which produce many elegant soft structures such as
      micelles, vesicle, nanotubes and fibres etc. 

PMID- 25375093
TI  - Molecular characterization of the monoclonal antibodies composing ZMAb: a
      protective cocktail against Ebola virus.
AB  - Ebola virus (EBOV) causes severe viral hemorrhagic fever in humans and non-human
      primates, with a case fatality rate of up to 88% in human outbreaks. Over the
      past 3 years, monoclonal antibody (mAb) cocktails have demonstrated high efficacy
      as treatments against EBOV infection. One such cocktail is ZMAb, which consists
      of three mouse antibodies, 1H3, 2G4, and 4G7. Here, we present the epitope
      binding properties of mAbs 1H3, 2G4, and 4G7. We showed that these antibodies
      have different variable region sequences, suggesting that the individual mAbs are
      not clonally related. All three antibodies were found to neutralize EBOV variant
      Mayinga. Additionally, 2G4 and 4G7 were shown to cross-inhibit each other in
      vitro and select for an escape mutation at the same position on the EBOV
      glycoprotein (GP), at amino acid 508. 1H3 selects an escape mutant at amino acid
      273 on EBOV GP. Surface plasmon resonance studies showed that all three
      antibodies have dissociation constants on the order of 10(-7). In combination
      with previous studies evaluating the binding sites of other protective
      antibodies, our results suggest that antibodies targeting the GP1-GP2 interface
      and the glycan cap are often selected as efficacious antibodies for post-exposure
      interventions against EBOV. 

PMID- 25375095
TI  - Revealing structural changes of prion protein during conversion from alpha
      helical monomer to beta-oligomers by means of ESR and nanochannel encapsulation.
AB  - Under nondenaturing neutral pH conditions, full-length mouse recombinant prion
      protein lacking the only disulfide bridge can spontaneously convert from an alpha
      helical-dominant conformer (alpha-state) to a beta-sheet-rich conformer (beta
      state), which then associates into beta-oligomers, and the kinetics of this
      spontaneous conversion depends on the properties of the buffer used. The
      molecular details of this structural conversion have not been reported due to the
      difficulty of exploring big protein aggregates. We introduced spin probes into
      different structural segments (three helices and the loop between strand 1 and
      helix 1), and employed a combined approach of ESR spectroscopy and protein
      encapsulation in nanochannels to reveal local structural changes during the alpha
      to-beta transition. Nanochannels provide an environment in which prion protein
      molecules are isolated from each other, but the alpha-to-beta transition can
      still occur. By measuring dipolar interactions between spin probes during the
      transition, we showed that helix 1 and helix 3 retained their helicity, while
      helix 2 unfolded to form an extended structure. Moreover, our pulsed ESR results
      allowed clear discrimination between the intra- and intermolecular distances
      between spin labeled residues in helix 2 in the beta-oligomers, making it
      possible to demonstrate that the unfolded helix 2 segment lies at the association
      interface of the beta-oligomers to form cross-beta structure. 

PMID- 25375096
TI  - Reperfusion of areas of ischemia in central retinal vein occlusion - reply.

PMID- 25375097
TI  - Development and validation of a UPLC-MS/MS method to monitor cephapirin excretion
      in dairy cows following intramammary infusion.
AB  - Cephapirin, a cephalosporin antibiotic, is used by the majority of dairy farms in
      the US. Fecal and urinary excretion of cephapirin could introduce this compound
      into the environment when manure is land applied as fertilizer, and may cause
      development of bacterial resistance to antibiotics critical for human health. The
      environmental loading of cephapirin by the livestock industry remains un
      assessed, largely due to a lack of appropriate analytical methods. Therefore,
      this study aimed to develop and validate a cephapirin quantification method to
      capture the temporal pattern of cephapirin excretion in dairy cows following
      intramammary infusion. The method includes an extraction with phosphate buffer
      and methanol, solid-phase extraction (SPE) clean-up, and quantification using
      ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
      The LOQ values of the developed method were 4.02 ug kg(-1) and 0.96 ug L(-1) for
      feces and urine, respectively. This robust method recovered >60% and >80%
      cephapirin from spiked blank fecal and urine samples, respectively, with
      acceptable intra- and inter-day variation (<10%). Using this method, we detected
      trace amounts (ug kg(-1)) of cephapirin in dairy cow feces, and cephapirin in
      urine was detected at very high concentrations (133 to 480 ug L(-1)). Cephapirin
      was primarily excreted via urine and its urinary excretion was influenced by day
      (P = 0.03). Peak excretion (2.69 mg) was on day 1 following intramammary infusion
      and decreased sharply thereafter (0.19, 0.19, 0.08, and 0.17 mg on day 2, 3, 4,
      and 5, respectively) reflecting a quadratic pattern of excretion (Quadratic: P =
      0.03). The described method for quantification of cephapirin in bovine feces and
      urine is sensitive, accurate, and robust and allowed to monitor the pattern of
      cephapirin excretion in dairy cows. This data will help develop manure
      segregation and treatment methods to minimize the risk of antibiotic loading to
      the environment from dairy farms.

PMID- 25375098
TI  - Usnic acid potassium salt: an alternative for the control of Biomphalaria
      glabrata (Say, 1818).
AB  - In Brazil, the snail Biomphalaria glabrata is the most important vector of
      schistosomiasis due to its wide geographical distribution, high infection rate
      and efficient disease transmission. Among the methods of schistosomiasis control,
      the World Health Organization recommends the use of synthetic molluscicides, such
      as niclosamide. However, different substances of natural origin have been tested
      as alternatives for the control or eradication of mollusks. The literature
      describes the antitumor, antimicrobial and antiviral properties of usnic acid as
      well as other important activities of common interest between medicine and the
      environment. However, usnic acid has a low degree of water solubility, which can
      be a limiting factor for its use, especially in aquatic environments, since the
      organic solvents commonly used to solubilize this substance can have toxic
      effects on aquatic biota. Thus, the aim of the present study was to test the
      potassium salt of usnic acid (potassium usnate) with regard to molluscicidal
      activity and toxicity to brine shrimp (Artemia salina). To obtain potassium
      usnate, usnic acid was extracted with diethyl ether isolated and purified from
      the lichen Cladonia substellata. Biological assays were performed with embryos
      and adult snails of B. glabrata exposed for 24 h to the usnate solution
      solubilized in dechlorinated water at 2.5; 5 and 10 ug/ml for embryos, 0.5; 0.9;
      1;5 and 10 ug/ml for mollusks and 0.5; 1; 5; 10 ug/ml for A. salina. The lowest
      lethal concentration for the embryos and adult snails was 10 and 1 ug/ml,
      respectively. No toxicity to A. salina was found. The results show that modified
      usnic acid has increased solubility (100%) without losing its biological activity
      and may be a viable alternative for the control of B. glabrata. 

PMID- 25375100
TI  - Inference of epidemiological dynamics based on simulated phylogenies using birth
      death and coalescent models.
AB  - Quantifying epidemiological dynamics is crucial for understanding and forecasting
      the spread of an epidemic. The coalescent and the birth-death model are used
      interchangeably to infer epidemiological parameters from the genealogical
      relationships of the pathogen population under study, which in turn are inferred
      from the pathogen genetic sequencing data. To compare the performance of these
      widely applied models, we performed a simulation study. We simulated phylogenetic
      trees under the constant rate birth-death model and the coalescent model with a
      deterministic exponentially growing infected population. For each tree, we re
      estimated the epidemiological parameters using both a birth-death and a
      coalescent based method, implemented as an MCMC procedure in BEAST v2.0. In our
      analyses that estimate the growth rate of an epidemic based on simulated birth
      death trees, the point estimates such as the maximum a posteriori/maximum
      likelihood estimates are not very different. However, the estimates of
      uncertainty are very different. The birth-death model had a higher coverage than
      the coalescent model, i.e. contained the true value in the highest posterior
      density (HPD) interval more often (2-13% vs. 31-75% error). The coverage of the
      coalescent decreases with decreasing basic reproductive ratio and increasing
      sampling probability of infecteds. We hypothesize that the biases in the
      coalescent are due to the assumption of deterministic rather than stochastic
      population size changes. Both methods performed reasonably well when analyzing
      trees simulated under the coalescent. The methods can also identify other key
      epidemiological parameters as long as one of the parameters is fixed to its true
      value. In summary, when using genetic data to estimate epidemic dynamics, our
      results suggest that the birth-death method will be less sensitive to population
      fluctuations of early outbreaks than the coalescent method that assumes a
      deterministic exponentially growing infected population. 

PMID- 25375102
TI  - A developmental model for branching morphogenesis of lake cress compound leaf.
AB  - Lake cress, Rorippa aquatica (Brassicaceae), is a semi-aquatic plant that
      exhibits a variety of leaf shapes, from simple leaves to highly branched compound
      leaves, depending on the environment. Leaf shape can vary within a single plant,
      suggesting that the variation can be explained by a simple model. In order to
      simulate the branched structure in the compound leaves of R. aquatica, we
      implemented reaction-diffusion (RD) patterning onto a theoretical framework that
      had been developed for serration distribution in the leaves of Arabidopsis
      thaliana, with the modification of the one-dimensional reaction-diffusion domain
      being deformed with the spatial periodicity of the RD pattern while expanding.
      This simple method using an iterative pattern could create regular and nested
      branching patterns. Subsequently, we verified the plausibility of our theoretical
      model by comparing it with the experimentally observed branching patterns. The
      results suggested that our model successfully predicted both the qualitative and
      quantitative aspects of the timing and positioning of branching in growing R.
      aquatica leaves. 

PMID- 25375099
TI  - Strong agreement of nationally recommended retention measures from the Institute
      of Medicine and Department of Health and Human Services.
AB  - OBJECTIVE: We sought to quantify agreement between Institute of Medicine (IOM)
      and Department of Health and Human Services (DHHS) retention indicators, which
      have not been compared in the same population, and assess clinical retention
      within the largest HIV cohort collaboration in the U.S. DESIGN: Observational
      study from 2008-2010, using clinical cohort data in the North American AIDS
      Cohort Collaboration on Research and Design (NA-ACCORD). METHODS: Retention
      definitions used HIV primary care visits. The IOM retention indicator was: >=2
      visits, >=90 days apart, each calendar year. This was extended to a 2-year
      period; retention required meeting the definition in both years. The DHHS
      retention indicator was: >=1 visit each semester over 2 years, each >=60 days
      apart. Kappa statistics detected agreement between indicators and C statistics
      (areas under Receiver-Operating Characteristic curves) from logistic regression
      analyses summarized discrimination of the IOM indicator by the DHHS indicator.
      RESULTS: Among 36,769 patients in 2008-2009 and 34,017 in 2009-2010, there were
      higher percentages of participants retained in care under the IOM indicator than
      the DHHS indicator (80% vs. 75% in 2008-2009; 78% vs. 72% in 2009-2010,
      respectively) (p<0.01), persisting across all demographic and clinical
      characteristics (p<0.01). There was high agreement between indicators overall
      (kappa = 0.83 in 2008-2009; kappa = 0.79 in 2009-2010, p<0.001), and C statistics
      revealed a very strong ability to predict retention according to the IOM
      indicator based on DHHS indicator status, even within characteristic strata.
      CONCLUSIONS: Although the IOM indicator consistently reported higher retention in
      care compared with the DHHS indicator, there was strong agreement between IOM and
      DHHS retention indicators in a cohort demographically similar to persons living
      with HIV/AIDS in the U.S. Persons with poorer retention represent subgroups of
      interest for retention improvement programs nationally, particularly in light of
      the White House Executive Order on the HIV Care Continuum.

PMID- 25375101
TI  - Nox2 knockout delays infarct progression and increases vascular recovery through
      angiogenesis in mice following ischaemic stroke with reperfusion.
AB  - Evidence suggests the NADPH oxidases contribute to ischaemic stroke injury and
      Nox2 is the most widely studied subtype in the context of stroke. There is still
      conjecture however regarding the benefits of inhibiting Nox2 to improve stroke
      outcome. The current study aimed to examine the temporal effects of genetic Nox2
      deletion on neuronal loss after ischaemic stroke using knockout (KO) mice with 6,
      24 and 72 hour recovery. Transient cerebral ischaemia was induced via
      intraluminal filament occlusion and resulted in reduced infarct volumes in Nox2
      KO mice at 24 h post-stroke compared to wild-type controls. No protection was
      evident at either 6 h or 72 h post-stroke, with both genotypes exhibiting similar
      volumes of damage. Reactive oxygen species were detected using dihydroethidium
      and were co-localised with neurons and microglia in both genotypes using
      immunofluorescent double-labelling. The effect of Nox2 deletion on vascular
      damage and recovery was also examined 24 h and 72 h post-stroke using an antibody
      against laminin. Blood vessel density was decreased in the ischaemic core of both
      genotypes 24 h post-stroke and returned to pre-stroke levels only in Nox2 KO mice
      by 72 h. Overall, these results are the first to show that genetic Nox2 deletion
      merely delays the progression of neuronal loss after stroke but does not prevent
      it. Additionally, we show for the first time that Nox2 deletion increases re
      vascularisation of the damaged brain by 72 h, which may be important in promoting
      endogenous brain repair mechanisms that rely on re-vascularisation. 

PMID- 25375103
TI  - Transcriptomic analysis of the mussel Elliptio complanata identifies candidate
      stress-response genes and an abundance of novel or noncoding transcripts.
AB  - Mussels are useful indicator species of environmental stress and degradation, and
      the global decline in freshwater mussel diversity and abundance is of
      conservation concern. Elliptio complanata is a common freshwater mussel of
      eastern North America that can serve both as an indicator and as an experimental
      model for understanding mussel physiology and genetics. To support genetic
      components of these research goals, we assembled transcriptome contigs from
      Illumina paired-end reads. Despite efforts to collapse similar contigs, the final
      assembly was in excess of 136,000 contigs with an N50 of 982 bp. Even so,
      comparisons to the CEGMA database of conserved eukaryotic genes indicated that ~
      20% of genes remain unrepresented. However, numerous candidate stress-response
      genes were present, and we identified lineage-specific patterns of
      diversification among molluscs for cytochrome P450 detoxification genes and two
      saccharide-modifying enzymes: 1,3 beta-galactosyltransferase and
      fucosyltransferase. Less than a quarter of contigs had protein-level similarity
      based on modest BLAST and Hmmer3 statistical thresholds. These results add
      comparative genomic resources for molluscs and suggest a wealth of novel proteins
      and noncoding transcripts.

PMID- 25375104
TI  - First record of the myrmicine ant genus Meranoplus Smith, 1853 (Hymenoptera:
      Formicidae) from the Arabian Peninsula with description of a new species and
      notes on the zoogeography of southwestern Kingdom of [corrected] Saudi Arabia.
AB  - The ant genus Meranoplus is reported for the first time from the Arabian
      Peninsula (Kingdom of Saudi Arabia) by the new species M. pulcher sp. n., based
      on the worker caste. Specimens were collected from Al Sarawat and Asir Mountains
      of southwestern Kingdom of Saudi Arabia using pitfall traps. Meranoplus pulcher
      sp. n. is included in the Afrotropical M. magretii-group, with greatest
      similarity to M. magrettii Andre from Sudan. A key to the Afrotropical species of
      the M. magretii-group is presented. A brief review of the ant taxa with
      Afrotropical affinities in southwestern region of the Kingdom of Saudi Arabia is
      given. 

PMID- 25375105
TI  - Are morphometrics sufficient for estimating age of pre-fledging birds in the
      field? A test using common terns (Sterna hirundo).
AB  - Age is a key component of fitness, affecting survival and reproductive
      capacities. Where it is not possible to study known individuals from birth,
      morphometrics (predominantly patterns of plumage development for birds) are most
      often used to estimate age. Although criteria for age estimations exist for many
      species, the degree to which these criteria improve the precision of estimates
      remains to be tested, restricting their widespread acceptance. We develop a
      photographic tool for estimating ages of Common Tern (Sterna hirundo) chicks and
      test it using 100 human observers of varying prior experience across four
      breeding colonies (three North American sites and one European site) and under
      controlled laboratory conditions. We followed the design approach of other
      morphometric tools, expanding it to create a user-friendly guide (divided into
      six age groupings). The majority (86%) of observers improved in chick-aging
      accuracy when using the tool by an average of 20.1% (+/-1.4 SE) and correctly
      estimated 60.3% (+/-1.4) of chick ages. This was similar to the intrinsic aging
      ability of our best field observer (63.3%). Observers with limited experience
      showed the greatest increases in chick-aging accuracy over experienced observers
      who likely had established a method for estimating chick ages prior to using the
      tool. Even the best observers only correctly estimated ages of chicks 62.9% (+/
      2.8) of the time in the field and 84.0% (+/-2.9) of the time in the lab when
      using the tool and typically underestimated ages. This indicates that
      developmental variation between individual chicks can prevent completely reliable
      age estimates and corroborates the few existing data that suggest that
      morphometric criteria fail to achieve robust levels of accuracy and may introduce
      error into studies that rely on them. We conclude that novel approaches for
      estimating age, not only morphometric criteria, must be pursued. 

PMID- 25375106
TI  - The effect of stress on motor function in Drosophila.
AB  - Exposure to unpredictable and uncontrollable conditions causes animals to
      perceive stress and change their behavior. It is unclear how the perception of
      stress modifies the motor components of behavior and which molecular pathways
      affect the behavioral change. In order to understand how stress affects motor
      function, we developed an experimental platform that quantifies walking motions
      in Drosophila. We found that stress induction using electrical shock results in
      backwards motions of the forelegs at the end of walking strides. These leg
      retrogressions persisted during repeated stimulation, although they habituated
      substantially. The motions also continued for several strides after the end of
      the shock, indicating that stress induces a behavioral aftereffect. Such
      aftereffect could also be induced by restricting the motion of the flies via wing
      suspension. Further, the long-term effects could be amplified by combining either
      immobilization or electric shock with additional stressors. Thus, retrogression
      is a lingering form of response to a broad range of stressful conditions, which
      cause the fly to search for a foothold when it faces extreme and unexpected
      challenges. Mutants in the cAMP signaling pathway enhanced the stress response,
      indicating that this pathway regulates the behavioral response to stress. Our
      findings identify the effect of stress on a specific motor component of behavior
      and define the role of cAMP signaling in this stress response. 

PMID- 25375107
TI  - Programmed ribosomal frameshift alters expression of west nile virus genes and
      facilitates virus replication in birds and mosquitoes.
AB  - West Nile virus (WNV) is a human pathogen of significant medical importance with
      close to 40,000 cases of encephalitis and more than 1,600 deaths reported in the
      US alone since its first emergence in New York in 1999. Previous studies
      identified a motif in the beginning of non-structural gene NS2A of encephalitic
      flaviviruses including WNV which induces programmed -1 ribosomal frameshift (PRF)
      resulting in production of an additional NS protein NS1'. We have previously
      demonstrated that mutant WNV with abolished PRF was attenuated in mice. Here we
      have extended our previous observations by showing that PRF does not appear to
      have a significant role in virus replication, virion formation, and viral spread
      in several cell lines in vitro. However, we have also shown that PRF induces an
      over production of structural proteins over non-structural proteins in virus
      infected cells and that mutation abolishing PRF is present in ~11% of the wild
      type virus population. In vivo experiments in house sparrows using wild type and
      PRF mutant of New York 99 strain of WNV viruses showed some attenuation for the
      PRF mutant virus. Moreover, PRF mutant of Kunjin strain of WNV showed significant
      decrease compared to wild type virus infection in dissemination of the virus from
      the midgut through the haemocoel, and ultimately the capacity of infected
      mosquitoes to transmit virus. Thus our results demonstrate an important role for
      PRF in regulating expression of viral genes and consequently virus replication in
      avian and mosquito hosts. 

PMID- 25375108
TI  - A conserved peptide pattern from a widespread microbial virulence factor triggers
      pattern-induced immunity in Arabidopsis.
AB  - Microbe- or host damage-derived patterns mediate activation of pattern-triggered
      immunity (PTI) in plants. Microbial virulence factor (effector)-triggered
      immunity (ETI) constitutes a second layer of plant protection against microbial
      attack. Various necrosis and ethylene-inducing peptide 1 (Nep1)-like proteins
      (NLPs) produced by bacterial, oomycete and fungal microbes are phytotoxic
      virulence factors that exert immunogenic activities through phytotoxin-induced
      host cell damage. We here show that multiple cytotoxic NLPs also carry a pattern
      of 20 amino acid residues (nlp20) that triggers immunity-associated plant
      defenses and immunity to microbial infection in Arabidopsis thaliana and related
      plant species with similar characteristics as the prototype pattern, bacterial
      flagellin. Characteristic differences in flagellin and nlp20 plant responses
      exist however, as nlp20s fail to trigger extracellular alkalinization in
      Arabidopsis cell suspensions and seedling growth inhibition. Immunogenic nlp20
      peptide motifs are frequently found in bacterial, oomycete and fungal NLPs. Such
      an unusually broad taxonomic distribution within three phylogenetic kingdoms is
      unprecedented among microbe-derived triggers of immune responses in either
      metazoans or plants. Our findings suggest that cytotoxic NLPs carrying
      immunogenic nlp20 motifs trigger PTI in two ways as typical patterns and by
      inflicting host cell damage. We further propose that conserved structures within
      a microbial virulence factor might have driven the emergence of a plant pattern
      recognition system mediating PTI. As this is reminiscent of the evolution of
      immune receptors mediating ETI, our findings support the idea that there is a
      continuum between PTI and ETI. 

PMID- 25375109
TI  - The impact of Curtin University's activity, food and attitudes program on
      physical activity, sedentary time and fruit, vegetable and junk food consumption
      among overweight and obese adolescents: a waitlist controlled trial.
AB  - BACKGROUND: To determine the effects of participation in Curtin University's
      Activity, Food and Attitudes Program (CAFAP), a community-based, family-centered
      behavioural intervention, on the physical activity, sedentary time, and healthy
      eating behaviours of overweight and obese adolescents. METHODS: In this waitlist
      controlled clinical trial in Western Australia, adolescents (n = 69, 71% female,
      mean age 14.1 (SD 1.6) years) and parents completed an 8-week intervention
      followed by 12 months of telephone and text message support. Assessments were
      completed at baseline, before beginning the intervention, immediately following
      the intervention, and at 3-, 6-, and 12- months follow-up. The primary outcomes
      were physical activity and sedentary time assessed by accelerometers and servings
      of fruit, vegetables and junk food assessed by 3-day food records. RESULTS:
      During the intensive 8-week intervention sedentary time decreased by -5.1
      min/day/month (95% CI: -11.0, 0.8) which was significantly greater than the rate
      of change during the waitlist period (p = .014). Moderate physical activity
      increased by 1.8 min/day/month (95% CI: -0.04, 3.6) during the intervention
      period, which was significantly greater than the rate of change during the
      waitlist period (p = .041). Fruit consumption increased during the intervention
      period (monthly incidence rate ratio (IRR) 1.3, 95% CI: 1.10, 1.56) and junk food
      consumption decreased (monthly IRR 0.8, 95% CI: 0.74, 0.94) and these changes
      were different to those seen during the waitlist period (p = .004 and p = .020
      respectively). CONCLUSIONS: Participating in CAFAP appeared to have a positive
      influence on the physical activity, sedentary and healthy eating behaviours of
      overweight and obese adolescents and many of these changes were maintained for
      one year following the intensive intervention. TRIAL REGISTRATION: Australia and
      New Zealand Clinical Trials Registry ACTRN12611001187932.

PMID- 25375110
TI  - A germline polymorphism of thymine DNA glycosylase induces genomic instability
      and cellular transformation.
AB  - Thymine DNA glycosylase (TDG) functions in base excision repair, a DNA repair
      pathway that acts in a lesion-specific manner to correct individual damaged or
      altered bases. TDG preferentially catalyzes the removal of thymine and uracil
      paired with guanine, and is also active on 5-fluorouracil (5-FU) paired with
      adenine or guanine. The rs4135113 single nucleotide polymorphism (SNP) of TDG is
      found in 10% of the global population. This coding SNP results in the alteration
      of Gly199 to Ser. Gly199 is part of a loop responsible for stabilizing the
      flipped abasic nucleotide in the active site pocket. Biochemical analyses
      indicate that G199S exhibits tighter binding to both its substrate and abasic
      product. The persistent accumulation of abasic sites in cells expressing G199S
      leads to the induction of double-strand breaks (DSBs). Cells expressing the G199S
      variant also activate a DNA damage response. When expressed in cells, G199S
      induces genomic instability and cellular transformation. Together, these results
      suggest that individuals harboring the G199S variant may have increased risk for
      developing cancer. 

PMID- 25375111
TI  - The complete mitochondrial genome of Aix galericulata and Tadorna ferruginea:
      bearings on their phylogenetic position in the Anseriformes.
AB  - Aix galericulata and Tadorna ferruginea are two Anatidae species representing
      different taxonomic groups of Anseriformes. We used a PCR-based method to
      determine the complete mtDNAs of both species, and estimated phylogenetic trees
      based on the complete mtDNA alignment of these and 14 other Anseriforme species,
      to clarify Anseriform phylogenetics. Phylogenetic trees were also estimated using
      a multiple sequence alignment of three mitochondrial genes (Cyt b, ND2, and COI)
      from 68 typical species in GenBank, to further clarify the phylogenetic
      relationships of several groups among the Anseriformes. The new mtDNAs are
      circular molecules, 16,651 bp (Aix galericulata) and 16,639 bp (Tadorna
      ferruginea) in length, containing the 37 typical genes, with an identical gene
      order and arrangement as those of other Anseriformes. Comparing the protein
      coding genes among the mtDNAs of 16 Anseriforme species, ATG is generally the
      start codon, TAA is the most frequent stop codon, one of three, TAA, TAG, and T-,
      commonly observed. All tRNAs could be folded into canonical cloverleaf secondary
      structures except for tRNASer (AGY) and tRNALeu (CUN), which are missing the
      "DHU" arm.Phylogenetic relationships demonstrate that Aix galericula and Tadorna
      ferruginea are in the same group, the Tadorninae lineage, based on our analyses
      of complete mtDNAs and combined gene data. Molecular phylogenetic analysis
      suggests the 68 species of Anseriform birds be divided into three families:
      Anhimidae, Anatidae, and Anseranatidae. The results suggest Anatidae birds be
      divided into five subfamilies: Anatinae, Tadorninae, Anserinae, Oxyurinae, and
      Dendrocygninae. Oxyurinae and Dendrocygninae should not belong to Anserinae, but
      rather represent independent subfamilies. The Anatinae includes species from the
      tribes Mergini, Somaterini, Anatini, and Aythyini. The Anserinae includes species
      from the tribes Anserini and Cygnini. 

PMID- 25375112
TI  - [High intensity aerobic interval training improves peak oxygen consumption in
      patients with metabolic syndrome: CAT].
AB  - INTRODUCTION: A number of cardiovascular risk factors characterizes the metabolic
      syndrome: insulin resistance (IR), low HDL cholesterol and high triglycerides.
      The aforementioned risk factors lead to elevated levels of abdominal adipose
      tissue, resulting in oxygen consumption deficiency. PURPOSE: To verify the
      validity and applicability of using high intensity interval training (HIIT) in
      subjects with metabolic syndrome and to answer the following question: Can HIIT
      improve peak oxygen consumption? METHOD: The systematic review "Effects of
      aerobic interval training on exercise capacity and metabolic risk factors in
      individuals with cardiometabolic disorders" was analyzed. RESULTS: Data suggests
      high intensity aerobic interval training increases peak oxygen consumption by a
      standardized mean difference of 3.60 mL/kg-1/min-1 (95% confidence interval, 0.28
      4.91). CONCLUSION: In spite of the methodological shortcomings of the primary
      studies included in the systematic review, we reasonably conclude that
      implementation of high intensity aerobic interval training in subjects with
      metabolic syndrome, leads to increases in peak oxygen consumption.

PMID- 25375113
TI  - Selenium accumulation in unicellular green alga Chlorella vulgaris and its
      effects on antioxidant enzymes and content of photosynthetic pigments.
AB  - The aim of the present study was to investigate selenite effects in the
      unicellular green algae Chlorella vulgaris as a primary producer and the
      relationship with intracellular bioaccumulation. The effects of selenite were
      evaluated by measuring the effect of different selenite concentrations on algal
      growth during a 144 h exposure period. It was found that lower Se concentrations
      (<= 75 mg L(-1)) positively promoted C. vulgaris growth and acted as antioxidant
      by inhibiting lipid peroxidation (LPO) and intracellular reactive oxygen species
      (ROS). The antioxidative effect was associated with an increase in guaiacol
      peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD) and photosynthetic
      pigments. Meanwhile, significant increase in the cell growth rate and organic Se
      content was also detected in the algae. In contrast, these changes were opposite
      in C. vulgaris exposed to Se higher than 100 mg L-1. The antioxidation and
      toxicity appeared to be correlated to Se bioaccumulation, which suggests the
      appropriate concentration of Se in the media accumulation of C. vulgaris should
      be 75 mg L-1. Taken together, C. vulgaris possesses tolerance to Se, and Se
      Chlorella could be developed as antioxidative food for aquaculture and human
      health.

PMID- 25375114
TI  - [Cold-water immersion versus passive therapy to decrease delayed onset muscular
      soreness: a CAT].
AB  - INTRODUCTION: Late onset muscle soreness, also known as delayed onset muscle
      soreness, is a painful musculoskeletal condition that may occur 24-48 and up to
      72 hours after the completion of unusual physical or high intensity exercise
      involving eccentric muscle activity. In the field of physical rehabilitation,
      immersion in cold water is a common intervention mainly used in sports medicine,
      to minimize delayed onset muscle soreness and promote recovery after exercise.
      OBJECTIVES: To assess the validity and applicability of the results regarding the
      effectiveness of immersion in cold water after high intensity exercise and answer
      the following question: In subjects who exercise regularly, can cold-water
      immersion compared to passive therapy (rest) reduce late-onset muscle soreness?
      METHODS: The article "Cold Water Immersion (cryotherapy) for preventing and
      treating muscle soreness after exercise," a Cochrane systematic review authored
      by Bleakley et al (2012), was analyzed. RESULTS: Immersion in cold water can
      decrease delayed onset of muscle pain after high intensity exercise. Twenty-four
      hours after the intervention, the mean standardized difference was -0.55 (95% CI:
      -0.84 to -0.27); 48 hours after, the mean standardized difference was -0.66 (95%
      CI: -0.97 to -0.35); 72 hours after, the mean standardized difference was -0.93
      (95% CI: -1.36 to -0.51) and up to 96 hours after, mean standardized difference
      was -0.58 (95% CI: -1.00 to -0.16). CONCLUSION: Despite the methodological
      limitations present in the studies included in the systematic review analyzed, we
      found the recommendation for cold water immersion (cryotherapy) reasonable in
      individuals with late muscle pain caused by high intensity sports.

PMID- 25375115
TI  - Menthol inhibits detrusor contractility independently of TRPM8 activation.
AB  - Agonists such as icilin and menthol can activate the cool temperature-sensitive
      ion channel TRPM8. However, biological responses to menthol may occur
      independently of TRPM8 activation. In the rodent urinary bladder, menthol
      facilitates the micturition reflex but inhibits muscarinic contractions of the
      detrusor smooth muscle. The site(s) of TRPM8 expression in the bladder are
      controversial. In this study we investigated the regulation of bladder
      contractility in vitro by menthol. Bladder strips from wild type and TRPM8
      knockout male mice (25-30 g) were dissected free and mounted in organ baths.
      Isometric contractions to carbachol (1 nM-30 uM), CaCl2 (1 uM to 100 mM) and
      electrical field stimulation (EFS; 8, 16, 32 Hz) were measured. Strips from both
      groups contracted similarly in response to both carbachol and EFS. Menthol (300
      uM) or nifedipine (1 uM) inhibited carbachol and EFS-induced contractions in both
      wild type and TRPM8 knockout bladder strips. Incubation with the sodium channel
      blocker tetrodotoxin (1 uM), replacement of extracellular sodium with the
      impermeant cation N-Methyl-D-Glucamine, incubation with a cocktail of potassium
      channel inhibitors (100 nM charybdotoxin, 1 uM apamin, 10 uM glibenclamide and 1
      uM tetraethylammonium) or removal of the urothelium did not affect the inhibitory
      actions of menthol. Contraction to CaCl2 was markedly inhibited by either menthol
      or nifedipine. In cultured bladder smooth muscle cells, menthol or nifedipine
      abrogated the carbachol or KCl-induced increases in [Ca2+]i. Intravesical
      administration of menthol increased voiding frequency while decreasing peak
      voiding pressure. We conclude that menthol inhibits muscarinic bladder
      contractions through blockade of L-type calcium channels, independently of TRPM8
      activation. 

PMID- 25375116
TI  - Impact of genetic counseling and Connexin-26 and Connexin-30 testing on deaf
      identity and comprehension of genetic test results in a sample of deaf adults: a
      prospective, longitudinal study.
AB  - Using a prospective, longitudinal study design, this paper addresses the impact
      of genetic counseling and testing for deafness on deaf adults and the Deaf
      community. This study specifically evaluated the effect of genetic counseling and
      Connexin-26 and Connexin-30 genetic test results on participants' deaf identity
      and understanding of their genetic test results. Connexin-26 and Connexin-30
      genetic testing was offered to participants in the context of linguistically and
      culturally appropriate genetic counseling. Questionnaire data collected from 209
      deaf adults at four time points (baseline, immediately following pre-test genetic
      counseling, 1-month following genetic test result disclosure, and 6-months after
      result disclosure) were analyzed. Four deaf identity orientations (hearing,
      marginal, immersion, bicultural) were evaluated using subscales of the Deaf
      Identity Development Scale-Revised. We found evidence that participants
      understood their specific genetic test results following genetic counseling, but
      found no evidence of change in deaf identity based on genetic counseling or their
      genetic test results. This study demonstrated that culturally and linguistically
      appropriate genetic counseling can improve deaf clients' understanding of genetic
      test results, and the formation of deaf identity was not directly related to
      genetic counseling or Connexin-26 and Connexin-30 genetic test results. 

PMID- 25375117
TI  - Coincident helminth infection modulates systemic inflammation and immune
      activation in active pulmonary tuberculosis.
AB  - BACKGROUND: Helminth infections are known to modulate innate and adaptive immune
      responses in active and latent tuberculosis (TB). However, the role of helminth
      infections in modulating responses associated with inflammation and immune
      activation (reflecting disease activity and/or severity) in TB is not known.
      METHODOLOGY: We measured markers of inflammation and immune activation in active
      pulmonary TB individuals (ATB) with co-incidental Strongyloides stercoralis (Ss)
      infection. These included systemic levels of acute phase proteins, matrix
      metalloproteinases and their endogenous inhibitors and immune activation markers.
      As a control, we measured the systemic levels of the same molecules in TB
      uninfected individuals (NTB) with or without Ss infection. PRINCIPAL FINDINGS:
      Our data confirm that ATB is associated with elevated levels of the various
      measured molecules when compared to those seen in NTB. Our data also reveal that
      co-incident Ss infection in ATB individuals is associated with significantly
      decreased circulating levels of acute phase proteins, matrix metalloproteinases,
      tissue inhibitors of matrix metalloproteinases as well as the systemic immune
      activation markers, sCD14 and sCD163. These changes are specific to ATB since
      they are absent in NTB individuals with Ss infection. CONCLUSIONS: Our data
      therefore reveal a profound effect of Ss infection on the markers associated with
      TB disease activity and severity and indicate that co-incidental helminth
      infections might dampen the severity of TB disease.

PMID- 25375118
TI  - Enhanced tissue factor expression by blood eosinophils from patients with
      hypereosinophilia: a possible link with thrombosis.
AB  - Thrombotic risk is increased in eosinophil-mediated disorders, and several
      hypotheses have been proposed to link eosinophilia and thrombosis. In particular,
      eosinophils have been described as source of tissue factor (TF), the main
      initiator of blood coagulation; however, this aspect is still controversial. This
      study was aimed to evaluate whether TF expression varies in eosinophils isolated
      from normal subjects and patients with different hypereosinophilic conditions.
      Eosinophils were immunologically purified from peripheral blood samples of 9
      patients with different hypereosinophilic conditions and 9 normal subjects.
      Western blot analysis and real-time polymerase chain reaction (RT-PCR) were
      performed to test eosinophil TF expression. For comparison, TF expression was
      evaluated in monocytes from blood donors and in human endothelial (ECV304) and
      fibroblast (IMR90) cell lines. Western blot analysis revealed a major band of
      47,000 corresponding to native TF in homogenates of purified eosinophils with a
      higher intensity in the 9 patients than in the 9 controls (p<0.0001). According
      to RT-PCR cycle threshold (Ct), TF gene expression was higher in eosinophils from
      patients than in those from controls, median (range) 35.10 (19.45-36.50) vs 37.17
      (35.33-37.87) (p = 0.002), and was particularly abundant in one patient with
      idiopathic hypereosinophilic syndrome and ischemic heart attacks (Ct: 19.45). TF
      gene expression was moderate in monocytes, Ct: 31.32 (29.82-33.49) and abundant
      in endothelial cells, Ct: 28.70 (27.79-29.57) and fibroblasts, Ct: 22.77 (19.22
      25.05). Our results indicate that human blood eosinophils contain variable
      amounts of TF. The higher TF expression in patients with hypereosinophilic
      disorders may contribute to increase the thrombotic risk. 

PMID- 25375119
TI  - Epidemiology of dengue disease in the Philippines (2000-2011): a systematic
      literature review.
AB  - This literature analysis describes the available dengue epidemiology data in the
      Philippines between 2000 and 2011. Of 253 relevant data sources identified, 34,
      including additional epidemiology data provided by the National Epidemiology
      Center, Department of Health, Philippines, were reviewed. There were 14
      publications in peer reviewed journals, and 17 surveillance reports/sources,
      which provided variable information from the passive reporting system and show
      broad trends in dengue incidence, including age group predominance and disease
      severity. The peer reviewed studies focused on clinical severity of cases, some
      revealed data on circulating serotypes and genotypes and on the seroepidemiology
      of dengue including incidence rates for infection and apparent disease. Gaps in
      the data were identified, and include the absence incidence rates stratified by
      age, dengue serotype and genotype distribution, disease severity data, sex
      distribution data, and seroprevalence data.

PMID- 25375120
TI  - Mouse hair cycle expression dynamics modeled as coupled mesenchymal and
      epithelial oscillators.
AB  - The hair cycle is a dynamic process where follicles repeatedly move through
      phases of growth, retraction, and relative quiescence. This process is an example
      of temporal and spatial biological complexity. Understanding of the hair cycle
      and its regulation would shed light on many other complex systems relevant to
      biological and medical research. Currently, a systematic characterization of gene
      expression and summarization within the context of a mathematical model is not
      yet available. Given the cyclic nature of the hair cycle, we felt it was
      important to consider a subset of genes with periodic expression. To this end, we
      combined several mathematical approaches with high-throughput, whole mouse skin,
      mRNA expression data to characterize aspects of the dynamics and the possible
      cell populations corresponding to potentially periodic patterns. In particular
      two gene clusters, demonstrating properties of out-of-phase synchronized
      expression, were identified. A mean field, phase coupled oscillator model was
      shown to quantitatively recapitulate the synchronization observed in the data.
      Furthermore, we found only one configuration of positive-negative coupling to be
      dynamically stable, which provided insight on general features of the regulation.
      Subsequent bifurcation analysis was able to identify and describe alternate
      states based on perturbation of system parameters. A 2-population mixture model
      and cell type enrichment was used to associate the two gene clusters to features
      of background mesenchymal populations and rapidly expanding follicular epithelial
      cells. Distinct timing and localization of expression was also shown by RNA and
      protein imaging for representative genes. Taken together, the evidence suggests
      that synchronization between expanding epithelial and background mesenchymal
      cells may be maintained, in part, by inhibitory regulation, and potential
      mediators of this regulation were identified. Furthermore, the model suggests
      that impairing this negative regulation will drive a bifurcation which may
      represent transition into a pathological state such as hair miniaturization. 

PMID- 25375121
TI  - Pseudoautosomal region 1 length polymorphism in the human population.
AB  - The human sex chromosomes differ in sequence, except for the pseudoautosomal
      regions (PAR) at the terminus of the short and the long arms, denoted as PAR1 and
      PAR2. The boundary between PAR1 and the unique X and Y sequences was established
      during the divergence of the great apes. During a copy number variation screen,
      we noted a paternally inherited chromosome X duplication in 15 independent
      families. Subsequent genomic analysis demonstrated that an insertional
      translocation of X chromosomal sequence into the Y chromosome generates an
      extended PAR [corrected].The insertion is generated by non-allelic homologous
      recombination between a 548 bp LTR6B repeat within the Y chromosome PAR1 and a
      second LTR6B repeat located 105 kb from the PAR boundary on the X chromosome. The
      identification of the reciprocal deletion on the X chromosome in one family and
      the occurrence of the variant in different chromosome Y haplogroups demonstrate
      this is a recurrent genomic rearrangement in the human population. This finding
      represents a novel mechanism shaping sex chromosomal evolution.

PMID- 25375122
TI  - Eribulin mesylate targets human telomerase reverse transcriptase in ovarian
      cancer cells.
AB  - Treatment of advanced ovarian cancer involves platinum-based chemotherapy.
      However, chemoresistance is a major obstacle. Cancer stem cells (CSCs) are
      thought to be one of the causes of chemoresistance, but the underlying mechanism
      remains elusive. Recently, human telomerase reverse transcriptase (hTERT) has
      been reported to promote CSC-like traits. In this study, we found that a mitotic
      inhibitor, eribulin mesylate (eribulin), effectively inhibited growth of platinum
      resistant ovarian cancer cell lines. Eribulin-sensitive cells showed a higher
      efficiency for sphere formation, suggesting that these cells possess an enhanced
      CSC-like phenotype. Moreover, these cells expressed a higher level of hTERT, and
      suppression of hTERT expression by siRNA resulted in decreased sensitivity to
      eribulin, suggesting that hTERT may be a target for eribulin. Indeed, we found
      that eribulin directly inhibited RNA-dependent RNA polymerase (RdRP) activity,
      but not telomerase activity of hTERT in vitro. We propose that eribulin targets
      the RdRP activity of hTERT and may be an effective therapeutic option for CSCs.
      Furthermore, hTERT may be a useful biomarker to predict clinical responses to
      eribulin. 

PMID- 25375123
TI  - A tri-modality image fusion method for target delineation of brain tumors in
      radiotherapy.
AB  - PURPOSE: To develop a tri-modality image fusion method for better target
      delineation in image-guided radiotherapy for patients with brain tumors. METHODS:
      A new method of tri-modality image fusion was developed, which can fuse and
      display all image sets in one panel and one operation. And a feasibility study in
      gross tumor volume (GTV) delineation using data from three patients with brain
      tumors was conducted, which included images of simulation CT, MRI, and 18F
      fluorodeoxyglucose positron emission tomography (18F-FDG PET) examinations before
      radiotherapy. Tri-modality image fusion was implemented after image registrations
      of CT+PET and CT+MRI, and the transparency weight of each modality could be
      adjusted and set by users. Three radiation oncologists delineated GTVs for all
      patients using dual-modality (MRI/CT) and tri-modality (MRI/CT/PET) image fusion
      respectively. Inter-observer variation was assessed by the coefficient of
      variation (COV), the average distance between surface and centroid (ADSC), and
      the local standard deviation (SDlocal). Analysis of COV was also performed to
      evaluate intra-observer volume variation. RESULTS: The inter-observer variation
      analysis showed that, the mean COV was 0.14(+/- 0.09) and 0.07(+/- 0.01) for dual
      modality and tri-modality respectively; the standard deviation of ADSC was
      significantly reduced (p<0.05) with tri-modality; SDlocal averaged over median
      GTV surface was reduced in patient 2 (from 0.57 cm to 0.39 cm) and patient 3
      (from 0.42 cm to 0.36 cm) with the new method. The intra-observer volume
      variation was also significantly reduced (p = 0.00) with the tri-modality method
      as compared with using the dual-modality method. CONCLUSION: With the new tri
      modality image fusion method smaller inter- and intra-observer variation in GTV
      definition for the brain tumors can be achieved, which improves the consistency
      and accuracy for target delineation in individualized radiotherapy.

PMID- 25375124
TI  - Effects of danshensu on platelet aggregation and thrombosis: in vivo
      arteriovenous shunt and venous thrombosis models in rats.
AB  - Danshensu, a type of dihydroxyphenyl lactic acid, is one of the most abundant
      active phenolic acids in the dried root of Salvia miltiorrhizae (Lamiaceae)-
      widely used traditional Chinese medicine. The effects of danshensu on platelet
      aggregation and thrombus formation in rats were examined using various methods.
      It was found that danshensu significantly reduced thrombus weight in 2
      experimental thrombosis models; dose-dependent inhibition of adenosine
      diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation occurred
      in normal and blood stasis-induced rats; Danshensu also significantly mitigated
      blood viscosity, plasma viscosity and hematocrit levels. Moreover, danshensu
      significantly inhibited venous thrombosis-induced expression of cyclooxygenases-2
      (COX-2) rather than cyclooxygenases-1(COX-1) in the venous walls, down regulated
      thromboxane B2 (TXB2) and up regulated 6-keto prostaglandin F1alpha (6-keto
      PGF1alpha), normalizing the TXB2/6-keto-PGF1alpha ratio. In addition, danshensu
      did not induce gastric lesions and even had protective effects on aspirin-induced
      ulcer formation at doses as high as 60 mg/kg. These findings suggest that the
      antithrombotic and antiplatelet aggregation effects of danshensu are attributed
      to its highly selective inhibition of COX-2 and ability to normalize the
      thromboxane A2(TXA2)/prostacyclin(PGI2) balance. These findings suggest that
      danshensu have great prospects in antithrombotic and antiplatelet therapy.

PMID- 25375126
TI  - Introducing a new series: evidence-based decision-making.
AB  - A patient comes to your office with repeated unwanted and intrusive thoughts that
      prevent her from conducting her daily life activities and that make her anxious.
      You apply a simple screening and conclude that she may have an obsessive
      compulsive disorder. The work-up rules out other less frequent causes of similar
      manifestations and a more formal diagnostic interview confirms your clinical
      suspicion. What are the best treatment options you can offer your patient and how
      successful are they?

PMID- 25375125
TI  - Arginase 2 deficiency prevents oxidative stress and limits hyperoxia-induced
      retinal vascular degeneration.
AB  - BACKGROUND: Hyperoxia exposure of premature infants causes obliteration of the
      immature retinal microvessels, leading to a condition of proliferative
      vitreoretinal neovascularization termed retinopathy of prematurity (ROP).
      Previous work has demonstrated that the hyperoxia-induced vascular injury is
      mediated by dysfunction of endothelial nitric oxide synthase resulting in
      peroxynitrite formation. This study was undertaken to determine the involvement
      of the ureahydrolase enzyme arginase in this pathology. METHODS AND FINDINGS:
      Studies were performed using hyperoxia-treated bovine retinal endothelial cells
      (BRE) and mice with oxygen-induced retinopathy (OIR) as experimental models of
      ROP. Treatment with the specific arginase inhibitor 2(S)-amino-6-boronohexanoic
      acid (ABH) prevented hyperoxia-induced apoptosis of BRE cells and reduced vaso
      obliteration in the OIR model. Furthermore, deletion of the arginase 2 gene
      protected against hyperoxia-induced vaso-obliteration, enhanced physiological
      vascular repair, and reduced retinal neovascularization in the OIR model.
      Additional deletion of one copy of arginase 1 did not improve the vascular
      pathology. Analyses of peroxynitrite by quantitation of its biomarker
      nitrotyrosine, superoxide by dihydroethidium imaging and NO formation by
      diaminofluoroscein imaging showed that the protective actions of arginase 2
      deletion were associated with blockade of superoxide and peroxynitrite formation
      and normalization of NOS activity. CONCLUSIONS: Our data demonstrate the
      involvement of arginase activity and arginase 2 expression in hyperoxia-induced
      vascular injury. Arginase 2 deletion prevents hyperoxia-induced retinal vascular
      injury by preventing NOS uncoupling resulting in decreased reactive oxygen
      species formation and increased nitric oxide bioavailability.

PMID- 25375127
TI  - The folding of the specific DNA recognition subdomain of the sleeping beauty
      transposase is temperature-dependent and is required for its binding to the
      transposon DNA.
AB  - The reaction of DNA transposition begins when the transposase enzyme binds to the
      transposon DNA. Sleeping Beauty is a member of the mariner family of DNA
      transposons. Although it is an important tool in genetic applications and has
      been adapted for human gene therapy, its molecular mechanism remains obscure.
      Here, we show that only the folded conformation of the specific DNA recognition
      subdomain of the Sleeping Beauty transposase, the PAI subdomain, binds to the
      transposon DNA. Furthermore, we show that the PAI subdomain is well folded at low
      temperatures, but the presence of unfolded conformation gradually increases at
      temperatures above 15 degrees C, suggesting that the choice of temperature may be
      important for the optimal transposase activity. Overall, the results provide a
      molecular-level insight into the DNA recognition by the Sleeping Beauty
      transposase. 

PMID- 25375129
TI  - Prognoses and long-term outcomes of nasopharyngeal carcinoma in Han and Uyghur
      patients treated with intensity-modulated radiotherapy in the Xinjiang Autonomous
      Region of China.
AB  - OBJECTIVES: The objective of this study was to investigate the long-term outcomes
      and prognostic factors for nasopharyngeal carcinoma (NPC) in Han and Uyghur
      patients treated with intensity-modulated radiotherapy (IMRT) in the Xinjiang
      region of China. MATERIALS AND METHODS: One hundred twenty-one Han and 60 Uyghur
      patients with newly diagnosed NPC without distant metastasis received IMRT at the
      Affiliated Tumor Hospital of Xinjiang Medical University between 2005 and 2008.
      The Kaplan-Meier method was used to estimate survival rates, and the log-rank
      test was used to evaluate differences in survival. RESULTS: Comparing Han and
      Uyghur patients, the 5-year overall survival (OS), disease-free survival (DFS),
      local control (LC), regional control (RC), and distant metastasis-free survival
      (DMFS) rates were 81.9% vs 77.6% (P = 0.297), 72.1% vs 65.6% (P = 0.493), 88.3%
      vs 86.5% (P = 0.759), 95.0% vs 94.6% (P = 0.929), and 79.1% vs 75.2% (P = 0.613),
      respectively. Multivariate Cox proportional hazards regression identified the
      following independent prognostic factors in Han patients: N stage (P = 0.007) and
      age (P = 0.028) for OS, and age (P = 0.028) for DFS. OS differed significantly
      between Han and Uyghur patients >60 years old group (P = 0.036). Among Uyghur
      patients, the independent prognostic factors were age for OS (P = 0.033), as well
      as N stage (P = 0.037) and age (P = 0.021) for DFS. Additionally, Uyghur patients
      were less likely to experience mucositis and dermatitis than Han patients.
      CONCLUSION: Han and Uyghur patients with NPC had statistically significant
      differences in age, smoking history, and N staging. There was no significant
      difference in overall treatment outcomes with IMRT between these 2 ethnic
      populations in Xinjiang, China.

PMID- 25375128
TI  - Co-dependence of HTLV-1 p12 and p8 functions in virus persistence.
AB  - HTLV-1 orf-I is linked to immune evasion, viral replication and persistence.
      Examining the orf-I sequence of 160 HTLV-1-infected individuals; we found
      polymorphism of orf-I that alters the relative amounts of p12 and its cleavage
      product p8. Three groups were identified on the basis of p12 and p8 expression:
      predominantly p12, predominantly p8 and balanced expression of p12 and p8. We
      found a significant association between balanced expression of p12 and p8 with
      high viral DNA loads, a correlate of disease development. To determine the
      individual roles of p12 and p8 in viral persistence, we constructed infectious
      molecular clones expressing p12 and p8 (D26), predominantly p12 (G29S) or
      predominantly p8 (N26). As we previously showed, cells expressing N26 had a
      higher level of virus transmission in vitro. However, when inoculated into Rhesus
      macaques, cells producing N26 virus caused only a partial seroconversion in 3 of
      4 animals and only 1 of those animals was HTLV-1 DNA positive by PCR. None of the
      animals exposed to G29S virus seroconverted or had detectable viral DNA. In
      contrast, 3 of 4 animals exposed to D26 virus seroconverted and were HTLV-1
      positive by PCR. In vitro studies in THP-1 cells suggested that expression of p8
      was sufficient for productive infection of monocytes. Since orf-I plays a role in
      T-cell activation and recognition; we compared the CTL response elicited by CD4+
      T-cells infected with the different HTLV-1 clones. Although supernatant p19
      levels and viral DNA loads for all four infected lines were similar, a
      significant difference in Tax-specific HLA.A2-restricted killing was observed.
      Cells infected with Orf-I-knockout virus (12KO), G29S or N26 were killed by CTLs,
      whereas cells infected with D26 virus were resistant to CTL killing. These
      results indicate that efficient viral persistence and spread require the combined
      functions of p12 and p8. 

PMID- 25375130
TI  - Transgene detection by digital droplet PCR.
AB  - Somatic gene therapy is a promising tool for the treatment of severe diseases.
      Because of its abuse potential for performance enhancement in sports, the World
      Anti-Doping Agency (WADA) included the term 'gene doping' in the official list of
      banned substances and methods in 2004. Several nested PCR or qPCR-based
      strategies have been proposed that aim at detecting long-term presence of
      transgene in blood, but these strategies are hampered by technical limitations.
      We developed a digital droplet PCR (ddPCR) protocol for Insulin-Like Growth
      Factor 1 (IGF1) detection and demonstrated its applicability monitoring 6 mice
      injected into skeletal muscle with AAV9-IGF1 elements and 2 controls over a 33
      day period. A duplex ddPCR protocol for simultaneous detection of Insulin-Like
      Growth Factor 1 (IGF1) and Erythropoietin (EPO) transgenic elements was created.
      A new DNA extraction procedure with target-orientated usage of restriction
      enzymes including on-column DNA-digestion was established. In vivo data revealed
      that IGF1 transgenic elements could be reliably detected for a 33-day period in
      DNA extracted from whole blood. In vitro data indicated feasibility of IGF1 and
      EPO detection by duplex ddPCR with high reliability and sensitivity. On-column
      DNA-digestion allowed for significantly improved target detection in downstream
      PCR-based approaches. As ddPCR provides absolute quantification, it ensures
      excellent day-to-day reproducibility. Therefore, we expect this technique to be
      used in diagnosing and monitoring of viral and bacterial infection, in detecting
      mutated DNA sequences as well as profiling for the presence of foreign genetic
      material in elite athletes in the future. 

PMID- 25375131
TI  - Cigarette smoking promotes inflammation in patients with COPD by affecting the
      polarization and survival of Th/Tregs through up-regulation of muscarinic
      receptor 3 and 5 expression.
AB  - BACKGROUND: CD4+ T cells in the lung are involved in the pathogenesis of chronic
      obstructive pulmonary disease (COPD), although CD4+ T cell subsets and the direct
      effect of smoking on these cells, especially the expression of MRs, have not been
      comprehensively examined. METHODS: First, circulating CD4+ T cell subsets in
      healthy nonsmokers, patients with SCOPD and patients with AECOPD were evaluated
      by flow cytometry. Then, differentiation experiments were carried out using RT
      PCR, and Ki-67/Annexin V antibodies were used to measure proliferation and
      apoptosis. We also explored the impact of CSE on the differentiation and survival
      of CD4+Th/Tregs and examined the expression of MRs in healthy nonsmokers and
      patients with SCOPD. RESULTS: We found the percentages of circulating Th1 and
      Th17 cells were increased in patients with AECOPD, while the percentage of Th2
      cells was decreased in patients with SCOPD. The percentages of Th10 cells were
      decreased in both patients with SCOPD and patients with AECOPD, while the
      percentages of Tregs were increased. In addition, the percentages of CD4+alpha-7+
      T cells were decreased in patients with SCOPD and patients with AECOPD. However,
      only the decrease observed in patients with AECOPD was significant. In vitro
      studies also revealed MR expression affected the polarization of T cells, with
      different CD4+ T cell subtypes acquiring different MR expression profiles. The
      addition of CSE facilitated CD4+ T cell polarization towards pro-inflammatory
      subsets (Th1 and Th17) and affected the survival of CD4+ T cells and Treg cells
      by up-regulating the expression of MR3 and 5, resulting in an imbalance of CD4+ T
      cell subsets. CONCLUSIONS: Our findings suggest an imbalance of circulating CD4+
      T cell subsets is involved in COPD pathogenesis in smokers. Cigarette smoking may
      contribute to this imbalance by affecting the polarization and survival of
      Th/Tregs through the up-regulation of MR3 and MR5.

PMID- 25375132
TI  - Hyper-brain networks support romantic kissing in humans.
AB  - Coordinated social interaction is associated with, and presumably dependent on,
      oscillatory couplings within and between brains, which, in turn, consist of an
      interplay across different frequencies. Here, we introduce a method of network
      construction based on the cross-frequency coupling (CFC) and examine whether
      coordinated social interaction is associated with CFC within and between brains.
      Specifically, we compare the electroencephalograms (EEG) of 15 heterosexual
      couples during romantic kissing to kissing one's own hand, and to kissing one
      another while performing silent arithmetic. Using graph-theory methods, we
      identify theta-alpha hyper-brain networks, with alpha serving a cleaving or
      pacemaker function. Network strengths were higher and characteristic path lengths
      shorter when individuals were kissing each other than when they were kissing
      their own hand. In both partner-oriented kissing conditions, greater strength and
      shorter path length for 5-Hz oscillation nodes correlated reliably with greater
      partner-oriented kissing satisfaction. This correlation was especially strong for
      inter-brain connections in both partner-oriented kissing conditions but not
      during kissing one's own hand. Kissing quality assessed after the kissing with
      silent arithmetic correlated reliably with intra-brain strength of 10-Hz
      oscillation nodes during both romantic kissing and kissing with silent
      arithmetic. We conclude that hyper-brain networks based on CFC may capture neural
      mechanisms that support interpersonally coordinated voluntary action and bonding
      behavior. 

PMID- 25375133
TI  - Niacin activates the PI3K/Akt cascade via PKC- and EGFR-transactivation-dependent
      pathways through hydroxyl-carboxylic acid receptor 2.
AB  - Niacin has been demonstrated to activate a PI3K/Akt signaling cascade to prevent
      brain damage after stroke and UV-induced skin damage; however, the underlying
      molecular mechanisms for HCA2-induced Akt activation remain to be elucidated.
      Using CHO-K1 cells stably expressing HCA2 and A431 cells, a human epidermoid cell
      line with high levels of endogenous expression of functional HCA2 receptors, we
      first demonstrated that niacin induced a robust Akt phosphorylation at both
      Thr308 and Ser473 in a time-dependent fashion, with a maximal activation at 5 min
      and a subsequent reduction to baseline by 30 min through HCA2, and that the
      activation was significantly blocked by pertussis toxin. The HCA2-mediated
      activation of Akt was also significantly inhibited by the PKC inhibitors
      GF109203x and Go6983 in both cell lines, by the PDGFR-selective inhibitor
      tyrphostin A9 in CHO-HCA2 cells and by the MMP inhibitor GM6001 and EGFR-specific
      inhibitor AG1478 in A431 cells. These results suggest that the PKC pathway and
      PDGFR/EGFR transactivation pathway play important roles in HCA2-mediated Akt
      activation. Further investigation indicated that PI3K and the Gbetagamma subunit
      were likely to play an essential role in HCA2-induced Akt activation. Moreover,
      Immunobloting analyses using an antibody that recognizes p70S6K1 phosphorylated
      at Thr389 showed that niacin evoked p70S6K1 activation via the PI3K/Akt pathway.
      The results of our study provide new insight into the signaling pathways involved
      in HCA2 activation.

PMID- 25375134
TI  - The relationship between species diversity and genetic structure in the rare
      Picea chihuahuana tree species community, Mexico.
AB  - Species diversity and genetic diversity, the most basic elements of biodiversity,
      have long been treated as separate topics, although populations evolve within a
      community context. Recent studies on community genetics and ecology have
      suggested that genetic diversity is not completely independent of species
      diversity. The Mexican Picea chihuahuana Martinez is an endemic species listed as
      "Endangered" on the Red List. Forty populations of Chihuahua spruce have been
      identified. This species is often associated with tree species of eight genera in
      gallery forests. This rare Picea chihuahuana tree community covers an area no
      more than 300 ha and has been subject of several studies involving different
      topics such as ecology, genetic structure and climate change. The overall aim of
      these studies was to obtain a dataset for developing management tools to help
      decision makers implement preservation and conservation strategies. However, this
      unique forest tree community may also represent an excellent subject for helping
      us to understand the interplay between ecological and evolutionary processes in
      determining community structure and dynamics. The AFLP technique and species
      composition data were used together to test the hypothesis that species diversity
      is related to the adaptive genetic structure of some dominant tree species (Picea
      chihuahuana, Pinus strobiformis, Pseudotsuga menziesii and Populus tremuloides)
      of the Picea chihuahuana tree community at fourteen locations. The Hill numbers
      were used as a diversity measure. The results revealed a significant correlation
      between tree species diversity and genetic structure in Populus tremuloides.
      Because the relationship between the two levels of diversity was found to be
      positive for the putative adaptive AFLP detected, genetic and species structures
      of the tree community were possibly simultaneously adapted to a combination of
      ecological or environmental factors. The present findings indicate that
      interactions between genetic variants and species diversity may be crucial in
      shaping tree communities. 

PMID- 25375135
TI  - The dual-specificity phosphatase 2 (DUSP2) does not regulate obesity-associated
      inflammation or insulin resistance in mice.
AB  - Alterations in the immune cell profile and the induction of inflammation within
      adipose tissue are a hallmark of obesity in mice and humans. Dual-specificity
      phosphatase 2 (DUSP2) is widely expressed within the immune system and plays a
      key role promoting immune and inflammatory responses dependent on mitogen
      activated protein kinase (MAPK) activity. We hypothesised that the absence of
      DUSP2 would protect mice against obesity-associated inflammation and insulin
      resistance. Accordingly, male and female littermate mice that are either wild
      type (wt) or homozygous for a germ-line null mutation of the dusp2 gene (dusp2-/
      ) were fed either a standard chow diet (SCD) or high fat diet (HFD) for 12 weeks
      prior to metabolic phenotyping. Compared with mice fed the SCD, all mice
      consuming the HFD became obese, developed glucose intolerance and insulin
      resistance, and displayed increased macrophage recruitment and markers of
      inflammation in epididymal white adipose tissue. The absence of DUSP2, however,
      had no effect on the development of obesity or adipose tissue inflammation. Whole
      body insulin sensitivity in male mice was unaffected by an absence of DUSP2 in
      response to either the SCD or HFD; however, HFD-induced insulin resistance was
      slightly, but significantly, reduced in female dusp2-/- mice. In conclusion,
      DUSP2 plays no role in regulating obesity-associated inflammation and only a
      minor role in controlling insulin sensitivity following HFD in female, but not
      male, mice. These data indicate that rather than DUSP2 being a pan regulator of
      MAPK dependent immune cell mediated inflammation, it appears to differentially
      regulate inflammatory responses that have a MAPK component. 

PMID- 25375136
TI  - Deep supervised, but not unsupervised, models may explain IT cortical
      representation.
AB  - Inferior temporal (IT) cortex in human and nonhuman primates serves visual object
      recognition. Computational object-vision models, although continually improving,
      do not yet reach human performance. It is unclear to what extent the internal
      representations of computational models can explain the IT representation. Here
      we investigate a wide range of computational model representations (37 in total),
      testing their categorization performance and their ability to account for the IT
      representational geometry. The models include well-known neuroscientific object
      recognition models (e.g. HMAX, VisNet) along with several models from computer
      vision (e.g. SIFT, GIST, self-similarity features, and a deep convolutional
      neural network). We compared the representational dissimilarity matrices (RDMs)
      of the model representations with the RDMs obtained from human IT (measured with
      fMRI) and monkey IT (measured with cell recording) for the same set of stimuli
      (not used in training the models). Better performing models were more similar to
      IT in that they showed greater clustering of representational patterns by
      category. In addition, better performing models also more strongly resembled IT
      in terms of their within-category representational dissimilarities.
      Representational geometries were significantly correlated between IT and many of
      the models. However, the categorical clustering observed in IT was largely
      unexplained by the unsupervised models. The deep convolutional network, which was
      trained by supervision with over a million category-labeled images, reached the
      highest categorization performance and also best explained IT, although it did
      not fully explain the IT data. Combining the features of this model with
      appropriate weights and adding linear combinations that maximize the margin
      between animate and inanimate objects and between faces and other objects yielded
      a representation that fully explained our IT data. Overall, our results suggest
      that explaining IT requires computational features trained through supervised
      learning to emphasize the behaviorally important categorical divisions
      prominently reflected in IT. 

PMID- 25375137
TI  - Systematic analysis of the role of RNA-binding proteins in the regulation of RNA
      stability.
AB  - mRNA half-lives are transcript-specific and vary over a range of more than 100
      fold in eukaryotic cells. mRNA stabilities can be regulated by sequence-specific
      RNA-binding proteins (RBPs), which bind to regulatory sequence elements and
      modulate the interaction of the mRNA with the cellular RNA degradation machinery.
      However, it is unclear if this kind of regulation is sufficient to explain the
      large range of mRNA stabilities. To address this question, we examined the
      transcriptome of 74 Schizosaccharomyces pombe strains carrying deletions in non
      essential genes encoding predicted RBPs (86% of all such genes). We identified 25
      strains that displayed changes in the levels of between 4 and 104 mRNAs. The
      putative targets of these RBPs formed biologically coherent groups, defining
      regulons involved in cell separation, ribosome biogenesis, meiotic progression,
      stress responses and mitochondrial function. Moreover, mRNAs in these groups were
      enriched in specific sequence motifs in their coding sequences and untranslated
      regions, suggesting that they are coregulated at the posttranscriptional level.
      We performed genome-wide RNA stability measurements for several RBP mutants, and
      confirmed that the altered mRNA levels were caused by changes in their
      stabilities. Although RBPs regulate the decay rates of multiple regulons, only
      16% of all S. pombe mRNAs were affected in any of the 74 deletion strains. This
      suggests that other players or mechanisms are required to generate the observed
      range of RNA half-lives of a eukaryotic transcriptome. 

PMID- 25375138
TI  - Sensitivity and specificity of point-of-care rapid combination syphilis-HIV-HCV
      tests.
AB  - BACKGROUND: New rapid point-of-care (POC) tests are being developed that would
      offer the opportunity to increase screening and treatment of several infections,
      including syphilis. This study evaluated three of these new rapid POC tests at a
      site in Southern California. METHODS: Participants were recruited from a testing
      center in Long Beach, California. A whole blood specimen was used to evaluate the
      performance of the Dual Path Platform (DPP) Syphilis Screen & Confirm, DPP HIV
      Syphilis, and DPP HIV-HCV-Syphilis rapid tests. The gold-standard comparisons
      were Treponema pallidum passive particle agglutination (TPPA), rapid plasma
      reagin (RPR), HCV enzyme immunoassay (EIA), and HIV-1/2 EIA. RESULTS: A total of
      948 whole blood specimens were analyzed in this study. The sensitivity of the HIV
      tests ranged from 95.7-100% and the specificity was 99.7-100%. The sensitivity
      and specificity of the HCV test were 91.8% and 99.3%, respectively. The
      treponemal-test sensitivity when compared to TPPA ranged from 44.0-52.7% and
      specificity was 98.7-99.6%. The non-treponemal test sensitivity and specificity
      when compared to RPR was 47.8% and 98.9%, respectively. The sensitivity of the
      Screen & Confirm test improved to 90.0% when cases who were both treponemal and
      nontreponemal positive were compared to TPPA+/RPR >= 1 ? 8. CONCLUSIONS: The HIV
      and HCV on the multi-infection tests showed good performance, but the treponemal
      and nontreponemal tests had low sensitivity. These results could be due to a low
      prevalence of active syphilis in the sample population because the sensitivity
      improved when the gold standard was limited to those more likely to be active
      cases. Further evaluation of the new syphilis POC tests is required before
      implementation into testing programs.

PMID- 25375139
TI  - Synergistic effect of high charge and energy particle radiation and chronological
      age on biomarkers of oxidative stress and tissue degeneration: a ground-based
      study using the vertebrate laboratory model organism Oryzias latipes.
AB  - High charge and energy (HZE) particles are a main hazard of the space radiation
      environment. Uncertainty regarding their health effects is a limiting factor in
      the design of human exploration-class space missions, that is, missions beyond
      low earth orbit. Previous work has shown that HZE exposure increases cancer risk
      and elicits other aging-like phenomena in animal models. Here, we investigate how
      a single exposure to HZE particle radiation, early in life, influences the
      subsequent age-dependent evolution of oxidative stress and appearance of
      degenerative tissue changes. Embryos of the laboratory model organism, Oryzias
      latipes (Japanese medaka fish), were exposed to HZE particle radiation at doses
      overlapping the range of anticipated human exposure. A separate cohort was
      exposed to reference gamma-radiation. Survival was monitored for 750 days, well
      beyond the median lifespan. The population was also sampled at intervals and
      liver tissue was subjected to histological and molecular analysis. HZE particle
      radiation dose and aging contributed synergistically to accumulation of lipid
      peroxidation products, which are a marker of chronic oxidative stress. This was
      mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co
      activator required for expression of oxidative stress defense genes and for
      mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria
      had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic
      lesions. Depending on the endpoint, effects of gamma-rays in the same dose range
      were either lesser or not detected. Results provide a quantitative and
      qualitative framework for understanding relative contributions of HZE particle
      radiation exposure and aging to chronic oxidative stress and tissue degeneration.

PMID- 25375140
TI  - The relationship between host lifespan and pathogen reservoir potential: an
      analysis in the system Arabidopsis thaliana--cucumber mosaic virus.
AB  - Identification of the determinants of pathogen reservoir potential is central to
      understand disease emergence. It has been proposed that host lifespan is one such
      determinant: short-lived hosts will invest less in costly defenses against
      pathogens, so that they will be more susceptible to infection, more competent as
      sources of infection and/or will sustain larger vector populations, thus being
      effective reservoirs for the infection of long-lived hosts. This hypothesis is
      sustained by analyses of different hosts of multihost pathogens, but not of
      different genotypes of the same host species. Here we examined this hypothesis by
      comparing two genotypes of the plant Arabidopsis thaliana that differ largely
      both in life-span and in tolerance to its natural pathogen Cucumber mosaic virus
      (CMV). Experiments with the aphid vector Myzus persicae showed that both
      genotypes were similarly competent as sources for virus transmission, but the
      short-lived genotype was more susceptible to infection and was able to sustain
      larger vector populations. To explore how differences in defense against CMV and
      its vector relate to reservoir potential, we developed a model that was run for a
      set of experimentally-determined parameters, and for a realistic range of host
      plant and vector population densities. Model simulations showed that the less
      efficient defenses of the short-lived genotype resulted in higher reservoir
      potential, which in heterogeneous host populations may be balanced by the longer
      infectious period of the long-lived genotype. This balance was modulated by the
      demography of both host and vector populations, and by the genetic composition of
      the host population. Thus, within-species genetic diversity for lifespan and
      defenses against pathogens will result in polymorphisms for pathogen reservoir
      potential, which will condition within-population infection dynamics. These
      results are relevant for a better understanding of host-pathogen co-evolution,
      and of the dynamics of pathogen emergence. 

PMID- 25375141
TI  - A novel modular bioreactor to in vitro study the hepatic sinusoid.
AB  - We describe a unique, versatile bioreactor consisting of two plates and a
      modified commercial porous membrane suitable for in vitro analysis of the liver
      sinusoid. The modular bioreactor allows i) excellent control of the cell seeding
      process; ii) cell culture under controlled shear stress stimulus, and; iii)
      individual analysis of each cell type upon completion of the experiment. The
      advantages of the bioreactor detailed here are derived from the modification of a
      commercial porous membrane with an elastomeric wall specifically moulded in order
      to define the cell culture area, to act as a gasket that will fit into the
      bioreactor, and to provide improved mechanical robustness. The device presented
      herein has been designed to simulate the in vivo organization of a liver sinusoid
      and tested by co-culturing endothelial cells (EC) and hepatic stellate cells
      (HSC). The results show both an optimal morphology of the endothelial cells as
      well as an improvement in the phenotype of stellate cells, most probably due to
      paracrine factors released from endothelial cells. This device is proposed as a
      versatile, easy-to-use co-culture system that can be applied to biomedical
      research of vascular systems, including the liver. 

PMID- 25375142
TI  - The CSN/COP9 signalosome regulates synaptonemal complex assembly during meiotic
      prophase I of Caenorhabditis elegans.
AB  - The synaptonemal complex (SC) is a conserved protein structure that holds
      homologous chromosome pairs together throughout much of meiotic prophase I. It is
      essential for the formation of crossovers, which are required for the proper
      segregation of chromosomes into gametes. The assembly of the SC is likely to be
      regulated by post-translational modifications. The CSN/COP9 signalosome has been
      shown to act in many pathways, mainly via the ubiquitin degradation/proteasome
      pathway. Here we examine the role of the CSN/COP9 signalosome in SC assembly in
      the model organism C. elegans. Our work shows that mutants in three subunits of
      the CSN/COP9 signalosome fail to properly assemble the SC. In these mutants, SC
      proteins aggregate, leading to a decrease in proper pairing between homologous
      chromosomes. The reduction in homolog pairing also results in an accumulation of
      recombination intermediates and defects in repair of meiotic DSBs to form the
      designated crossovers. The effect of the CSN/COP9 signalosome mutants on synapsis
      and crossover formation is due to increased neddylation, as reducing neddylation
      in these mutants can partially suppress their phenotypes. We also find a marked
      increase in apoptosis in csn mutants that specifically eliminates nuclei with
      aggregated SC proteins. csn mutants exhibit defects in germline proliferation,
      and an almost complete pachytene arrest due to an inability to activate the MAPK
      pathway. The work described here supports a previously unknown role for the
      CSN/COP9 signalosome in chromosome behavior during meiotic prophase I. 

PMID- 25375143
TI  - Analysis of nuclear export sequence regions of FUS-Related RNA-binding proteins
      in essential tremor.
AB  - BACKGROUND AND OBJECTIVE: Genes encoding RNA-binding proteins, including FUS and
      TDP43, play a central role in different neurodegenerative diseases such as
      amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Recently, a
      mutation located in the nuclear export signal (NES) of the FUS gene has been
      reported to cause an autosomal dominant form of familial Essential tremor.
      MATERIAL AND METHODS: We sequenced the exons coding the NES domains of five RNA
      binding proteins (TARDBP, hnRNPA2B1, hnRNPA1, TAF15 and EWSR1) that have been
      previously implicated in neurodegeneration in a series of 257 essential tremor
      (ET) cases and 376 healthy controls. We genotyped 404 additional ET subjects and
      510 healthy controls to assess the frequency of the EWSR1 p.R471C substitution.
      RESULTS: We identified a rare EWSR1 p.R471C substitution, which is highly
      conserved, in a single subject with familial ET. The pathogenicity of this
      substitution remains equivocal, as DNA samples from relatives were not available
      and the genotyping of 404 additional ET subjects did not reveal any further
      carriers. No other variants were observed with significant allele frequency
      differences compared to controls in the NES coding regions. CONCLUSIONS: The
      present study demonstrates that the NES domains of RNA-binding proteins are
      highly conserved. The role of the EWSR1 p.R471C substitution needs to be further
      evaluated in future studies.

PMID- 25375144
TI  - Magnetite nanoparticles inhibit tumor growth and upregulate the expression of
      p53/p16 in Ehrlich solid carcinoma bearing mice.
AB  - BACKGROUND: Magnetite nanoparticles (MNPs) have been widely used as contrast
      agents and have promising approaches in cancer treatment. In the present study we
      used Ehrlich solid carcinoma (ESC) bearing mice as a model to investigate MNPs
      antitumor activity, their effect on expression of p53 and p16 genes as an
      indicator for apoptotic induction in tumor tissues. METHOD: MNPs coated with
      ascorbic acid (size: 25.0+/-5.0 nm) were synthesized by co-precipitation method
      and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day
      by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor
      size, pathological changes and iron content in tumor and normal muscle tissues
      were assessed. We also assessed changes in expression levels of p53 and p16 genes
      in addition to p53 protein level by immunohistochemistry. RESULTS: Our results
      revealed that tumor growth was significantly reduced by IT and IP MNPs injection
      compared to untreated tumor. A significant increase in p53 and p16 mRNA
      expression was detected in Ehrlich solid tumors of IT and IP treated groups
      compared to untreated Ehrlich solid tumor. This increase was accompanied with
      increase in p53 protein expression. It is worth mentioning that no significant
      difference in expression of p53 and p16 could be detected between IT ESC and
      control group. CONCLUSION: MNPs might be more effective in breast cancer
      treatment if injected intratumorally to be directed to the tumor tissues.

PMID- 25375145
TI  - A prospective study of mortality from cryptococcal meningitis following treatment
      induction with 1200 mg oral fluconazole in Blantyre, Malawi.
AB  - OBJECTIVE: We have previously reported high ten-week mortality from cryptococcal
      meningitis in Malawian adults following treatment-induction with 800 mg oral
      fluconazole (57% [33/58]). National guidelines in Malawi and other African
      countries now advocate an increased induction dose of 1200 mg. We assessed
      whether this has improved outcomes. DESIGN: This was a prospective observational
      study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic
      lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then
      400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end
      point, and current results were compared with data from our prior patient cohort
      who started on fluconazole 800 mg/day. RESULTS: 47 participants received
      fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week
      mortality remained 55% (26/47). This was no better than our previous study
      (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77
      2.16, p = 0.332)). There was some evidence for improved survival in patients who
      had repeat lumbar punctures during early therapy to lower intracranial pressure
      (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]). CONCLUSION: There remains an urgent
      need to identify more effective, affordable and deliverable regimens for
      cryptococcal meningitis.

PMID- 25375147
TI  - Bt rice expressing Cry2Aa does not harm Cyrtorhinus lividipennis, a main predator
      of the nontarget herbivore Nilapavarta lugens.
AB  - T2A-1 is a newly developed transgenic rice that expresses a synthesized cry2Aa
      gene driven by the maize ubiquitin promoter. T2A-1 exhibits high resistance
      against lepidopteran pests of rice. The brown planthopper, Nilapavarta lugens
      (Stal), is a main nontarget sap-sucking insect pest of rice, and Cyrtorhinus
      lividipennis (Reuter) is the major predator of the eggs and young nymphs of
      planthoppers. As C. lividipennis may expose to the Cry2Aa protein via N. lugens,
      it is therefore essential to assess the potential effects of transgenic cry2Aa
      rice on this predator. In the present study, three experiments were conducted to
      evaluate the ecological risk of transgenic cry2Aa rice to C. lividipennis: (1) a
      direct feeding experiment in which C. lividipennis was fed an artificial diet
      containing Cry2Aa at the dose of 10-time higher than that it may encounter in the
      realistic field condition; (2) a tritrophic experiment in which the Cry2Aa
      protein was delivered to C. lividipennis indirectly through prey eggs or nymphs;
      (3) a realistic field experiment in which the population dynamics of C.
      lividipennis were investigated using vacuum-suction. Both direct exposure to
      elevated doses of the Cry2Aa protein and prey-mediated exposure to realistic
      doses of the protein did not result in significant detrimental effects on the
      development, survival, female ratio and body weight of C. lividipennis. No
      significant differences in population density and population dynamics were
      observed between C. lividipennis in transgenic cry2Aa and nontransgenic rice
      fields. It may be concluded that transgenic cry2Aa rice had no detrimental
      effects on C. lividipennis. This study represents the first report of an
      assessment continuum for the effects of transgenic cry2Aa rice on C.
      lividipennis.

PMID- 25375146
TI  - IL-37 inhibits inflammasome activation and disease severity in murine
      aspergillosis.
AB  - Since IL-37 transgenic mice possesses broad anti-inflammatory properties, we
      assessed whether recombinant IL-37 affects inflammation in a murine model of
      invasive pulmonary aspergillosis. Recombinant human IL-37 was injected
      intraperitoneally into mice prior to infection and the effects on lung
      inflammation and inflammasome activation were evaluated. IL-37 markedly reduced
      NLRP3-dependent neutrophil recruitment and steady state mRNA levels of IL-1beta
      production and mitigated lung inflammation and damage in a relevant clinical
      model, namely aspergillosis in mice with cystic fibrosis. The anti-inflammatory
      activity of IL-37 requires the IL-1 family decoy receptor TIR-8/SIGIRR. Thus, by
      preventing activation of the NLRP3 inflammasome and reducing IL-1beta secretion,
      IL-37 functions as a broad spectrum inhibitor of the innate response to infection
      mediated inflammation, and could be considered to be therapeutic in reducing the
      pulmonary damage due to non-resolving Aspergillus infection and disease. 

PMID- 25375148
TI  - [Family medicine and practice in the Mexican Social Security Institute].
AB  - The central ideas of this research paper are related to the practice of family
      medicine as a specialty. It focuses in its origins, problems, unique
      characteristics, limitations, scope, management, and processes within the context
      of primary care of the Mexican Social Security System. This approach was based on
      a qualitative, hermeneutical study closely related to the Structural
      Functionalism Theory. Within this framework, medical practice is seen as an
      equation: Meaning = action + function/structure. This offers an approach to the
      understanding of reality through surveys and observations in five categories:
      identity, activity, purpose, values/norms, and power/relationship. The practice
      of family medicine is defined as a medical act in the Mexican Social Security
      Institute. This act is limited to a brief encounter and a prescription, which
      makes it a short, fleeting, medicalized interaction. The result is a negative
      social imaginary of the physician, the patient and the whole of society. Thus,
      individuals and society host a negative social imaginary bestowed on doctors and
      users of the health system. 

PMID- 25375149
TI  - Evaluation of Ki67 expression across distinct categories of breast cancer
      specimens: a population-based study of matched surgical specimens, core needle
      biopsies and tissue microarrays.
AB  - INTRODUCTION: Tumor cell proliferation in breast cancer is strongly prognostic
      and may also predict response to chemotherapy. However, there is no consensus on
      counting areas or cut-off values for patient stratification. Our aim was to
      assess the matched level of proliferation by Ki67 when using different tissue
      categories (whole sections, WS; core needle biopsies, CNB; tissue microarrays,
      TMA), and the corresponding prognostic value. METHODS: We examined a
      retrospective, population-based series of breast cancer (n = 534) from the
      Norwegian Breast Cancer Screening Program. The percentage of Ki67 positive nuclei
      was evaluated by visual counting on WS (n = 534), CNB (n = 154) and TMA (n =
      459). RESULTS: The median percentage of Ki67 expression was 18% on WS (hot-spot
      areas), 13% on CNB, and 7% on TMA, and this difference was statistically
      significant in paired cases. Increased Ki67 expression by all evaluation methods
      was associated with aggressive tumor features (large tumor diameter, high
      histologic grade, ER negativity) and reduced patient survival. CONCLUSION: There
      is a significant difference in tumor cell proliferation by Ki67 across different
      sample categories. Ki67 is prognostic over a wide range of cut-off points and for
      different sample types, although Ki67 results derived from TMA sections are lower
      compared with those obtained using specimens from a clinical setting. Our
      findings indicate that specimen specific cut-off values should be applied for
      practical use.

PMID- 25375150
TI  - Average values and racial differences of neutrophil lymphocyte ratio among a
      nationally representative sample of United States subjects.
AB  - INTRODUCTION: Several studies reported the negative impact of elevated
      neutrophil/lymphocyte ratio (NLR) on outcomes in many surgical and medical
      conditions. Previous studies used arbitrary NLR cut-off points according to the
      average of the populations under study. There is no data on the average NLR in
      the general population. The aim of this study is to explore the average values of
      NLR and according to race in adult non-institutional United States individuals by
      using national data. METHODS: The National Health and Nutrition Examination
      Survey (NHANES) of aggregated cross-sectional data collected from 2007 to 2010
      was analyzed; data extracted included markers of systemic inflammation
      (neutrophil count, lymphocyte count, and NLR), demographic variables and other
      comorbidities. Subjects who were prescribed steroids, chemotherapy,
      immunomodulators and antibiotics were excluded. Adjusted linear regression models
      were used to examine the association between demographic and clinical
      characteristics and neutrophil counts, lymphocyte counts, and NLR. RESULTS:
      Overall 9427 subjects are included in this study. The average value of
      neutrophils is 4.3 k cells/mL, of lymphocytes 2.1k cells/mL; the average NLR is
      2.15. Non-Hispanic Black and Hispanic participants have significantly lower mean
      NLR values (1.76, 95% CI 1.71-1.81 and 2.08, 95% CI 2.04-2.12 respectively) when
      compared to non-Hispanic Whites (2.24, 95% CI 2.19-2.28-p<0.0001). Subjects who
      reported diabetes, cardiovascular disease, and smoking had significantly higher
      NLR than subjects who did not. Racial differences regarding the association of
      smoking and BMI with NLR were observed. CONCLUSIONS: This study is providing
      preliminary data on racial disparities in a marker of inflammation, NLR, that has
      been associated with several chronic diseases outcome, suggesting that different
      cut-off points should be set according to race. It also suggests that racial
      differences exist in the inflammatory response to environmental and behavioral
      risk factors.

PMID- 25375151
TI  - The prognostic value of excision repair cross-complementation group 1 (ERCC1) in
      patients with small cell lung cancer (SCLC) receiving platinum-based
      chemotherapy: evidence from meta-analysis.
AB  - Recently, the correlation between the efficacy of platinum-based chemotherapy and
      ERCC1 expression in patients with SCLC has attracted wide-spread attention, and a
      lot of investigations have been conducted, whereas conflicting results were
      presented. Therefore, we performed the present meta-analysis of eligible studies
      to derive a more precise evaluation of the association between ERCC1 expression
      and the clinical outcome in SCLC patients receiving platinum-based chemotherapy.
      A literature search for relevant studies was conducted in the electronic
      databases of PubMed, EMBASE and Web of Science. The inclusive criteria were SCLC
      patients treated by platinum-based chemotherapy, and evaluated the relationship
      between ERCC1 expression and the clinical outcomes [including overall response
      rate (ORR), overall survival (OS) or progression-free survival (PFS)]. Odds ratio
      (OR) or hazard ratio (HR) with 95% confidence interval (CI) was calculated to
      assess the risk. A total of nine studies including 1129 patients were included in
      final analysis. Our analysis indicated that positive/high ERCC1 expression was
      associated with unfavorable OS (HR = 1.18, 95%CI = 1.02-1.37) and PFS (HR = 1.46,
      95%CI = 1.14-1.88). Subgroup analysis according to disease stage suggested the
      significant relationship was found in limited stage (LS-SCLC), but not in
      extensive stage (ES-SCLC). However, no significant association was found between
      ERCC1 expression and ORR. Our analysis suggested ERCC1 expression may be a
      prognostic factor in SCLC patients receiving platinum-based chemotherapy,
      especially for LS-SCLC. 

PMID- 25375152
TI  - Ultrasound guidance for radial artery catheterization: an updated meta-analysis
      of randomized controlled trials.
AB  - BACKGROUND: Since a previous meta-analysis reported that ultrasound guidance was
      associated with a higher first-attempt success rate in catheterization of the
      radial artery, a number of randomized controlled trials (RCTs) have reported
      inconsistent results. The aim of the present study is to conduct an updated meta
      analysis to clarify the role of ultrasound guidance for radial artery
      catheterization. METHODS: A systematic literature search of PubMed, Embase, and
      Cochrane Central Register of Controlled Trials was conducted using specific
      search terms. Eligible studies were RCTs that compared ultrasound guidance with
      traditional palpation for radial artery catheterization. The Mantel-Haenszel
      method using the random effects model was adopted in this meta-analysis. RESULTS:
      Seven RCTs with 482 patients were included. Compared with traditional palpation,
      ultrasound guidance significantly increased the first-attempt success rate of
      radial artery catheterization (RR 1.51, 95% CI 1.07-2.14, P = 0.02). Subgroup
      analyses suggested that the superiority of ultrasound guidance for radial artery
      catheterization was significant when the technique was operated by experienced
      users, performed in small children and infants, and on elective procedures in the
      operating room. In addition, ultrasound guidance significantly reduced mean
      attempts to success (WMD -1.13, 95% CI -1.58 to -0.69, P<0.00001), mean-time to
      success (WMD -74.77s, 95% CI -137.89s to -11.64s, P = 0.02), and the occurrence
      of hematoma (RR 0.17, 95% CI 0.07-0.41, P = 0.0001). CONCLUSIONS: The present
      meta-analysis suggests a clear benefit from ultrasound guidance for radial artery
      catheterization compared with the traditional palpation. Preliminary training and
      familiarization with the ultrasound-guided technique is needed before applying it
      for radial artery catheterization, especially for inexperienced operators.

PMID- 25375153
TI  - Stability depends on positive autoregulation in Boolean gene regulatory networks.
AB  - Network motifs have been identified as building blocks of regulatory networks,
      including gene regulatory networks (GRNs). The most basic motif, autoregulation,
      has been associated with bistability (when positive) and with homeostasis and
      robustness to noise (when negative), but its general importance in network
      behavior is poorly understood. Moreover, how specific autoregulatory motifs are
      selected during evolution and how this relates to robustness is largely unknown.
      Here, we used a class of GRN models, Boolean networks, to investigate the
      relationship between autoregulation and network stability and robustness under
      various conditions. We ran evolutionary simulation experiments for different
      models of selection, including mutation and recombination. Each generation
      simulated the development of a population of organisms modeled by GRNs. We found
      that stability and robustness positively correlate with autoregulation; in all
      investigated scenarios, stable networks had mostly positive autoregulation.
      Assuming biological networks correspond to stable networks, these results suggest
      that biological networks should often be dominated by positive autoregulatory
      loops. This seems to be the case for most studied eukaryotic transcription factor
      networks, including those in yeast, flies and mammals. 

PMID- 25375154
TI  - Statin use is not associated with improved progression free survival in cetuximab
      treated KRAS mutant metastatic colorectal cancer patients: results from the
      CAIRO2 study.
AB  - Statins may inhibit the expression of the mutant KRAS phenotype by preventing the
      prenylation and thus the activation of the KRAS protein. This study was aimed at
      retrospectively evaluating the effect of statin use on outcome in KRAS mutant
      metastatic colorectal cancer patients (mCRC) treated with cetuximab. Treatment
      data were obtained from patients who were treated with capecitabine, oxaliplatin
      bevacizumab +/- cetuximab in the phase III CAIRO2 study. A total of 529 patients
      were included in this study, of whom 78 patients were on statin therapy. In
      patients with a KRAS wild type tumor (n = 321) the median PFS was 10.3 vs. 11.4
      months for non-users compared to statin users and in patients with a KRAS mutant
      tumor (n = 208) this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR)
      for PFS for statin users was 1.12 (95% confidence interval 0.78-1.61) and was not
      influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction.
      Statin use adjusted for covariates was not associated with increased PFS (HR =
      1.01, 95% confidence interval 0.71-1.54). In patients with a KRAS wild type tumor
      the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and
      in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was
      significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence
      interval 1.06-2.22). However, statin use, adjusted for covariates was not
      associated with increased OS (HR = 1.41, 95% confidence interval 0.95-2.10). In
      conclusion, the use of statins at time of diagnosis was not associated with an
      improved PFS in KRAS mutant mCRC patients treated with chemotherapy and
      bevacizumab plus cetuximab.

PMID- 25375155
TI  - Stress granule-defective mutants deregulate stress responsive transcripts.
AB  - To reduce expression of gene products not required under stress conditions,
      eukaryotic cells form large and complex cytoplasmic aggregates of RNA and
      proteins (stress granules; SGs), where transcripts are kept translationally
      inert. The overall composition of SGs, as well as their assembly requirements and
      regulation through stress-activated signaling pathways remain largely unknown. We
      have performed a genome-wide screen of S. cerevisiae gene deletion mutants for
      defects in SG formation upon glucose starvation stress. The screen revealed
      numerous genes not previously implicated in SG formation. Most mutants with
      strong phenotypes are equally SG defective when challenged with other stresses,
      but a considerable fraction is stress-specific. Proteins associated with SG
      defects are enriched in low-complexity regions, indicating that multiple weak
      macromolecule interactions are responsible for the structural integrity of SGs.
      Certain SG-defective mutants, but not all, display an enhanced heat-induced
      mutation rate. We found several mutations affecting the Ran GTPase, regulating
      nucleocytoplasmic transport of RNA and proteins, to confer SG defects.
      Unexpectedly, we found stress-regulated transcripts to reach more extreme levels
      in mutants unable to form SGs: stress-induced mRNAs accumulate to higher levels
      than in the wild-type, whereas stress-repressed mRNAs are reduced further in such
      mutants. Our findings are consistent with the view that, not only are SGs being
      regulated by stress signaling pathways, but SGs also modulate the extent of
      stress responses. We speculate that nucleocytoplasmic shuttling of RNA-binding
      proteins is required for gene expression regulation during stress, and that SGs
      modulate this traffic. The absence of SGs thus leads the cell to excessive, and
      potentially deleterious, reactions to stress. 

PMID- 25375156
TI  - Unravelling human trypanotolerance: IL8 is associated with infection control
      whereas IL10 and TNFalpha are associated with subsequent disease development.
AB  - In West Africa, Trypanosoma brucei gambiense, causing human African
      trypanosomiasis (HAT), is associated with a great diversity of infection
      outcomes. In addition to patients who can be diagnosed in the early hemolymphatic
      phase (stage 1) or meningoencephalitic phase (stage 2), a number of individuals
      can mount long-lasting specific serological responses while the results of
      microscopic investigations are negative (SERO TL+). Evidence is now increasing to
      indicate that these are asymptomatic subjects with low-grade parasitemia. The
      goal of our study was to investigate the type of immune response occurring in
      these "trypanotolerant" subjects. Cytokines levels were measured in healthy
      endemic controls (n = 40), stage 1 (n = 10), early stage 2 (n = 19), and late
      stage 2 patients (n = 23) and in a cohort of SERO TL+ individuals (n = 60) who
      were followed up for two years to assess the evolution of their parasitological
      and serological status. In contrast to HAT patients which T-cell responses
      appeared to be activated with increased levels of IL2, IL4, and IL10, SERO TL+
      exhibited high levels of proinflammatory cytokines (IL6, IL8 and TNFalpha) and an
      almost absence of IL12p70. In SERO TL+, high levels of IL10 and low levels of
      TNFalpha were associated with an increased risk of developing HAT whereas high
      levels of IL8 predicted that serology would become negative. Further studies
      using high throughput technologies, hopefully will provide a more detailed view
      of the critical molecules or pathways underlying the trypanotolerant phenotype. 

PMID- 25375157
TI  - The neural response to maternal stimuli: an ERP study.
AB  - Mothers are important to all humans. Research has established that maternal
      information affects individuals' cognition, emotion, and behavior. We measured
      event-related potentials (ERPs) to examine attentional and evaluative processing
      of maternal stimuli while participants completed a Go/No-go Association Task that
      paired mother or others words with good or bad evaluative words. Behavioral data
      showed that participants responded faster to mother words paired with good than
      the mother words paired with bad but showed no difference in response to these
      others across conditions, reflecting a positive evaluation of mother. ERPs showed
      larger P200 and N200 in response to mother than in response to others, suggesting
      that mother attracted more attention than others. In the subsequent time window,
      mother in the mother + bad condition elicited a later and larger late positive
      potential (LPP) than it did in the mother + good condition, but this was not true
      for others, also suggesting a positive evaluation of mother. These results
      suggest that people differentiate mother from others during initial attentional
      stage, and evaluative mother positively during later stage. 

PMID- 25375158
TI  - The central nervous system as target of Bacillus anthracis toxin independent
      virulence in rabbits and guinea pigs.
AB  - Infection of the central nervous system is considered a complication of Anthrax
      and was reported in humans and non-human primates. Previously we have reported
      that Bacillus anthracis possesses a toxin-independent virulent trait that, like
      the toxins, is regulated by the major virulence regulator, AtxA, in the presence
      of pXO2. This toxin-independent lethal trait is exhibited in rabbits and Guinea
      pigs following significant bacteremia and organ dissemination. Various findings,
      including meningitis seen in humans and primates, suggested that the CNS is a
      possible target for this AtxA-mediated activity. In order to penetrate into the
      brain tissue, the bacteria have to overcome the barriers isolating the CNS from
      the blood stream. Taking a systematic genetic approach, we compared intracranial
      (IC) inoculation and IV/SC inoculation for the outcome of the infection in
      rabbits/GP, respectively. The outstanding difference between the two models is
      exhibited by the encapsulated strain VollumDeltapXO1, which is lethal when
      injected IC, but asymptomatic when inoculated IV/SC. The findings demonstrate
      that there is an apparent bottleneck in the ability of mutants to penetrate into
      the brain. Any mutant carrying either pXO1 or pXO2 will kill the host upon IC
      injection, but only those carrying AtxA either on pXO1 or in the chromosome in
      the background of pXO2 can penetrate into the brain following peripheral
      inoculation. The findings were corroborated by histological examination by H&E
      staining and immunofluorescence of rabbits' brains following IV and IC
      inoculations. These findings may have major implications on future research both
      on B. anthracis pathogenicity and on vaccine development. 

PMID- 25375159
TI  - Approximation to the distribution of fitness effects across functional categories
      in human segregating polymorphisms.
AB  - Quantifying the proportion of polymorphic mutations that are deleterious or
      neutral is of fundamental importance to our understanding of evolution, disease
      genetics and the maintenance of variation genome-wide. Here, we develop an
      approximation to the distribution of fitness effects (DFE) of segregating single
      nucleotide mutations in humans. Unlike previous methods, we do not assume that
      synonymous mutations are neutral or not strongly selected, and we do not rely on
      fitting the DFE of all new nonsynonymous mutations to a single probability
      distribution, which is poorly motivated on a biological level. We rely on a
      previously developed method that utilizes a variety of published annotations
      (including conservation scores, protein deleteriousness estimates and regulatory
      data) to score all mutations in the human genome based on how likely they are to
      be affected by negative selection, controlling for mutation rate. We map this and
      other conservation scores to a scale of fitness coefficients via maximum
      likelihood using diffusion theory and a Poisson random field model on SNP data.
      Our method serves to approximate the deleterious DFE of mutations that are
      segregating, regardless of their genomic consequence. We can then compare the
      proportion of mutations that are negatively selected or neutral across various
      categories, including different types of regulatory sites. We observe that the
      distribution of intergenic polymorphisms is highly peaked at neutrality, while
      the distribution of nonsynonymous polymorphisms has a second peak at [Formula:
      see text]. Other types of polymorphisms have shapes that fall roughly in between
      these two. We find that transcriptional start sites, strong CTCF-enriched
      elements and enhancers are the regulatory categories with the largest proportion
      of deleterious polymorphisms. 

PMID- 25375160
TI  - Characterization of the YdeO regulon in Escherichia coli.
AB  - Enterobacteria are able to survive under stressful conditions within animals,
      such as acidic conditions in the stomach, bile salts during transfer to the
      intestine and anaerobic conditions within the intestine. The glutamate-dependent
      (GAD) system plays a major role in acid resistance in Escherichia coli, and
      expression of the GAD system is controlled by the regulatory cascade consisting
      of EvgAS > YdeO > GadE. To understand the YdeO regulon in vivo, we used ChIP-chip
      to interrogate the E. coli genome for candidate YdeO binding sites. All of the
      seven operons identified by ChIP-chip as being potentially regulated by YdeO were
      confirmed as being under the direct control of YdeO using RT-qPCR, EMSA, DNaseI
      footprinting and reporter assays. Within this YdeO regulon, we identified four
      stress-response transcription factors, DctR, NhaR, GadE, and GadW and enzymes for
      anaerobic respiration. Both GadE and GadW are involved in regulation of the GAD
      system and NhaR is an activator for the sodium/proton antiporter gene. In
      conjunction with co-transcribed Slp, DctR is involved in protection against
      metabolic endoproducts under acidic conditions. Taken all together, we suggest
      that YdeO is a key regulator of E. coli survival in both acidic and anaerobic
      conditions. 

PMID- 25375161
TI  - Uptake of aortic 18F-FDG is correlated with low-density lipoprotein cholesterol
      and leptin in a general population.
AB  - OBJECTIVE: This study investigated the relationship between aortic 18F-fluoro-2
      deoxy-D-glucose (18F-FDG) uptake and clinical and laboratory findings related to
      atherosclerosis in a general population. METHODS: 18F-FDG uptake in the ascending
      aorta was measured on the positron emission tomography/computed tomography
      (PET/CT) scans of 211 Japanese adults. The maximum target-to-background ratio
      (TBR) was compared with clinical and laboratory atherosclerosis findings.
      RESULTS: By multivariate regression analysis adjusted for age and sex, TBR
      ascending aorta (TBR-A) was significantly correlated with various clinical and
      laboratory parameters, such as body mass index, log visceral fat area, low
      density lipoprotein cholesterol (LDL-C), log fasting immunoreactive insulin, log
      homeostasis model assessment of insulin resistance, log total adiponectin and log
      leptin, in all subjects. Furthermore, by multivariate linear regression analysis
      adjusted for confounding factors, TBR-A was significantly correlated with LDL-C
      (beta = 0.001, p = 0.03) and log-leptin (beta = 0.336, p<0.01) in all subjects.
      CONCLUSION: TBR-A was significantly correlated with LDL-C and log-leptin
      independent from confounding factors. Our results suggest that aortic 18F-FDG
      uptake is a good marker of atherosclerosis, even in a general population.

PMID- 25375162
TI  - Epidemiological trends of dengue disease in Mexico (2000-2011): a systematic
      literature search and analysis.
AB  - This systematic literature review describes the epidemiology of dengue disease in
      Mexico (2000-2011). The annual number of uncomplicated dengue cases reported
      increased from 1,714 in 2000 to 15,424 in 2011 (incidence rates of 1.72 and 14.12
      per 100,000 population, respectively). Peaks were observed in 2002, 2007, and
      2009. Coastal states were most affected by dengue disease. The age distribution
      pattern showed an increasing number of cases during childhood, a peak at 10-20
      years, and a gradual decline during adulthood. All four dengue virus serotypes
      were detected. Although national surveillance is in place, there are knowledge
      gaps relating to asymptomatic cases, primary/secondary infections, and
      seroprevalence rates of infection in all age strata. Under-reporting of the
      clinical spectrum of the disease is also problematic. Dengue disease remains a
      serious public health problem in Mexico. 

PMID- 25375163
TI  - Functional analysis of Hyaloperonospora arabidopsidis RXLR effectors.
AB  - The biotrophic plant pathogen Hyaloperonospora arabidopsidis produces a set of
      putative effector proteins that contain the conserved RXLR motif. For most of
      these RXLR proteins the role during infection is unknown. Thirteen RXLR proteins
      from H. arabidopsidis strain Waco9 were analyzed for sequence similarities and
      tested for a role in virulence. The thirteen RXLR proteins displayed conserved N
      termini and this N-terminal conservation was also found in the 134 predicted RXLR
      genes from the genome of H. arabidopsidis strain Emoy2. To investigate the
      effects of single RXLR effector proteins on plant defense responses, thirteen H.
      arabidopsidis Waco9 RXLR genes were expressed in Arabidopsis thaliana.
      Subsequently, these plants were screened for altered susceptibility to the
      oomycetes H. arabidopsidis and Phytophthora capsici, and the bacterial pathogen
      Pseudomonas syringae. Additionally, the effect of the RXLR proteins on flg22
      triggered basal immune responses was assessed. Multifactorial analysis of results
      collated from all experiments revealed that, except for RXLR20, all RXLR effector
      proteins tested affected plant immunity. For RXLR9 this was confirmed using a P.
      syringae DeltaCEL-mediated effector delivery system. Together, the results show
      that many H. arabidopsidis RXLR effectors have small effects on the plant immune
      response, suggesting that suppression of host immunity by this biotrophic
      pathogen is likely to be caused by the combined actions of effectors. 

PMID- 25375164
TI  - Computational approaches for predicting biomedical research collaborations.
AB  - Biomedical research is increasingly collaborative, and successful collaborations
      often produce high impact work. Computational approaches can be developed for
      automatically predicting biomedical research collaborations. Previous works of
      collaboration prediction mainly explored the topological structures of research
      collaboration networks, leaving out rich semantic information from the
      publications themselves. In this paper, we propose supervised machine learning
      approaches to predict research collaborations in the biomedical field. We
      explored both the semantic features extracted from author research interest
      profile and the author network topological features. We found that the most
      informative semantic features for author collaborations are related to research
      interest, including similarity of out-citing citations, similarity of abstracts.
      Of the four supervised machine learning models (naive Bayes, naive Bayes
      multinomial, SVMs, and logistic regression), the best performing model is
      logistic regression with an ROC ranging from 0.766 to 0.980 on different
      datasets. To our knowledge we are the first to study in depth how research
      interest and productivities can be used for collaboration prediction. Our
      approach is computationally efficient, scalable and yet simple to implement. The
      datasets of this study are available at
      https://github.com/qingzhanggithub/medline-collaboration-datasets. 

PMID- 25375165
TI  - Differential effects of tissue culture coating substrates on prostate cancer cell
      adherence, morphology and behavior.
AB  - Weak cell-surface adhesion of cell lines to tissue culture surfaces is a common
      problem and presents technical limitations to the design of experiments. To
      overcome this problem, various surface coating protocols have been developed.
      However, a comparative and precise real-time measurement of their impact on cell
      behavior has not been conducted. The prostate cancer cell line LNCaP, derived
      from a patient lymph node metastasis, is a commonly used model system in prostate
      cancer research. However, the cells' characteristically weak attachment to the
      surface of tissue culture vessels and cover slips has impeded their manipulation
      and analysis and use in high throughput screening. To improve the adherence of
      LNCaP cells to the culture surface, we compared different coating reagents (poly
      L-lysine, poly-L-ornithine, collagen type IV, fibronectin, and laminin) and
      culturing conditions and analyzed their impact on cell proliferation, adhesion,
      morphology, mobility and gene expression using real-time technologies. The
      results showed that fibronectin, poly-L-lysine and poly-L-ornithine improved
      LNCaP cells adherence and provoked cell morphology alterations, such as increase
      of nuclear and cellular area. These coating reagents also induced a higher
      expression of F-actin and reduced cell mobility. In contrast, laminin and
      collagen type IV did not improve adherence but promoted cell aggregation and
      affected cell morphology. Cells cultured in the presence of laminin displayed
      higher mobility than control cells. All the coating conditions significantly
      affected cell viability; however, they did not affect the expression of androgen
      receptor-regulated genes. Our comparative findings provide important insight for
      the selection of the ideal coating reagent and culture conditions for the cancer
      cell lines with respect to their effect on proliferation rate, attachment,
      morphology, migration, transcriptional response and cellular cytoskeleton
      arrangement.

PMID- 25375166
TI  - Structural model of the hUbA1-UbcH10 quaternary complex: in silico and
      experimental analysis of the protein-protein interactions between E1, E2 and
      ubiquitin.
AB  - UbcH10 is a component of the Ubiquitin Conjugation Enzymes (Ubc; E2) involved in
      the ubiquitination cascade controlling the cell cycle progression, whereby
      ubiquitin, activated by E1, is transferred through E2 to the target protein with
      the involvement of E3 enzymes. In this work we propose the first three
      dimensional model of the tetrameric complex formed by the human UbA1 (E1), two
      ubiquitin molecules and UbcH10 (E2), leading to the transthiolation reaction. The
      3D model was built up by using an experimentally guided incremental docking
      strategy that combined homology modeling, protein-protein docking and refinement
      by means of molecular dynamics simulations. The structural features of the in
      silico model allowed us to identify the regions that mediate the recognition
      between the interacting proteins, revealing the active role of the ubiquitin
      crosslinked to E1 in the complex formation. Finally, the role of these regions
      involved in the E1-E2 binding was validated by designing short peptides that
      specifically interfere with the binding of UbcH10, thus supporting the
      reliability of the proposed model and representing valuable scaffolds for the
      design of peptidomimetic compounds that can bind selectively to Ubcs and inhibit
      the ubiquitylation process in pathological disorders. 

PMID- 25375168
TI  - Genetic diversity of Neisseria meningitidis serogroup C ST-4821 in China based on
      multiple-locus variable number tandem repeat analysis.
AB  - Neisseria meningitidis sequence type (ST)-4821 was first reported in China in
      2003, and a new hyper-virulent lineage has been designated as the ST-4821
      complex. A large number of N. meningitidis ST-4821 strains have been identified
      in China since 2003; however, the microevolution characteristics of this complex
      are unclear. Different combinations of variable number of tandem repeats (VNTR)
      loci were used in multiple-locus VNTR analysis (MLVA) to analyze 118 N.
      meningitidis serogroup C ST-4821 strains isolated from seventeen provinces
      between 2003 and 2012. Additionally, MLVA with five VNTR loci was performed due
      to its high discriminatory power. One hundred and eighteen isolates were found to
      comprise 112 subtypes based on MLVA, and 16 outbreak-associated strains were
      clustered into one group. These data indicate a high level of diversity for N.
      meningitidis ST-4821 due to microevolution in the last decade. In addition, the
      results revealed high similarity between isolates from the same geographic
      origins, which is helpful when monitoring the spread of N. meningitidis serogroup
      C ST-4821 and will provide valuable information for the control and prevention of
      bacterial meningitis in China. 

PMID- 25375169
TI  - Standardising and assessing digital images for use in clinical trials: a
      practical, reproducible method that blinds the assessor to treatment allocation.
AB  - With the increasing availability of high quality digital cameras that are easily
      operated by the non-professional photographer, the utility of using digital
      images to assess endpoints in clinical research of skin lesions has growing
      acceptance. However, rigorous protocols and description of experiences for
      digital image collection and assessment are not readily available, particularly
      for research conducted in remote settings. We describe the development and
      evaluation of a protocol for digital image collection by the non-professional
      photographer in a remote setting research trial, together with a novel
      methodology for assessment of clinical outcomes by an expert panel blinded to
      treatment allocation. 

PMID- 25375170
TI  - A gatekeeper chaperone complex directs translocator secretion during type three
      secretion.
AB  - Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver
      effector proteins into host cells. These protein delivery machines are composed
      of cytosolic components that recognize substrates and generate the force needed
      for translocation, the secretion conduit, formed by a needle complex and
      associated membrane spanning basal body, and translocators that form the pore in
      the target cell. A defined order of secretion in which needle component proteins
      are secreted first, followed by translocators, and finally effectors, is
      necessary for this system to be effective. While the secreted effectors vary
      significantly between organisms, the ~20 individual protein components that form
      the T3SS are conserved in many pathogenic bacteria. One such conserved protein,
      referred to as either a plug or gatekeeper, is necessary to prevent unregulated
      effector release and to allow efficient translocator secretion. The mechanism by
      which translocator secretion is promoted while effector release is inhibited by
      gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper,
      CopN, bound to a translocator-specific chaperone. The structure identifies a
      previously unknown interface between gatekeepers and translocator chaperones and
      reveals that in the gatekeeper-chaperone complex the canonical translocator
      binding groove is free to bind translocators. Structure-based mutagenesis of the
      homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator
      complex is essential for translocator secretion and for the ordered secretion of
      translocators prior to effectors. 

PMID- 25375171
TI  - More than just two sexes: the neural correlates of voice gender perception in
      gender dysphoria.
AB  - Gender dysphoria (also known as "transsexualism") is characterized as a
      discrepancy between anatomical sex and gender identity. Research points towards
      neurobiological influences. Due to the sexually dimorphic characteristics of the
      human voice, voice gender perception provides a biologically relevant function,
      e.g. in the context of mating selection. There is evidence for a better
      recognition of voices of the opposite sex and a differentiation of the sexes in
      its underlying functional cerebral correlates, namely the prefrontal and middle
      temporal areas. This fMRI study investigated the neural correlates of voice
      gender perception in 32 male-to-female gender dysphoric individuals (MtFs)
      compared to 20 non-gender dysphoric men and 19 non-gender dysphoric women.
      Participants indicated the sex of 240 voice stimuli modified in semitone steps in
      the direction to the other gender. Compared to men and women, MtFs showed
      differences in a neural network including the medial prefrontal gyrus, the
      insula, and the precuneus when responding to male vs. female voices. With
      increased voice morphing men recruited more prefrontal areas compared to women
      and MtFs, while MtFs revealed a pattern more similar to women. On a behavioral
      and neuronal level, our results support the feeling of MtFs reporting they cannot
      identify with their assigned sex. 

PMID- 25375172
TI  - Rapid recovery of cyanobacterial pigments in desiccated biological soil crusts
      following addition of water.
AB  - We examined soil surface colour change to green and hydrotaxis following addition
      of water to biological soil crusts using pigment extraction, hyperspectral
      imaging, microsensors and 13C labeling experiments coupled to matrix-assisted
      laser desorption and ionization time of flight-mass spectrometry (MALD-TOF MS).
      The topsoil colour turned green in less than 5 minutes following water addition.
      The concentrations of chlorophyll a (Chl a), scytonemin and echinenon rapidly
      increased in the top <1 mm layer while in the deeper layer, their concentrations
      remained low. Hyperspectral imaging showed that, in both wet and dehydrated
      crusts, cyanobacteria formed a layer at a depth of 0.2-0.4 mm and this layer did
      not move upward after wetting. 13C labeling experiments and MALDI TOF analysis
      showed that Chl a was already present in the desiccated crusts and de novo
      synthesis of this molecule started only after 2 days of wetting due to growth of
      cyanobacteria. Microsensor measurements showed that photosynthetic activity
      increased concomitantly with the increase of Chl a, and reached a maximum net
      rate of 92 umol m-2 h-1 approximately 2 hours after wetting. We conclude that the
      colour change of soil crusts to green upon water addition was not due to
      hydrotaxis but rather to the quick recovery and reassembly of pigments.
      Cyanobacteria in crusts can maintain their photosynthetic apparatus intact even
      under prolonged periods of desiccation with the ability to resume their
      photosynthetic activities within minutes after wetting. 

PMID- 25375173
TI  - Topography and land cover of watersheds predicts the distribution of the
      environmental pathogen Mycobacterium ulcerans in aquatic insects.
AB  - BACKGROUND: An understanding of the factors driving the distribution of pathogens
      is useful in preventing disease. Often we achieve this understanding at a local
      microhabitat scale; however the larger scale processes are often neglected. This
      can result in misleading inferences about the distribution of the pathogen,
      inhibiting our ability to manage the disease. One such disease is Buruli ulcer,
      an emerging neglected tropical disease afflicting many thousands in Africa,
      caused by the environmental pathogen Mycobacterium ulcerans. Herein, we aim to
      describe the larger scale landscape process describing the distribution of M.
      ulcerans. METHODOLOGY: Following extensive sampling of the community of aquatic
      macroinvertebrates in Cameroon, we select the 5 dominant insect Orders, and
      conduct an ecological niche model to describe how the distribution of M. ulcerans
      positive insects changes according to land cover and topography. We then explore
      the generalizability of the results by testing them against an independent
      dataset collected in a second endemic region, French Guiana. PRINCIPAL FINDINGS:
      We find that the distribution of the bacterium in Cameroon is accurately
      described by the land cover and topography of the watershed, that there are
      notable seasonal differences in distribution, and that the Cameroon model does
      not predict the distribution of M. ulcerans in French Guiana.
      CONCLUSIONS/SIGNIFICANCE: Future studies of M. ulcerans would benefit from
      consideration of local structure of the local stream network in future sampling,
      and further work is needed on the reasons for notable differences in the
      distribution of this species from one region to another. This work represents a
      first step in the identification of large-scale environmental drivers of this
      species, for the purposes of disease risk mapping.

PMID- 25375175
TI  - Exercise-mediated wall shear stress increases mitochondrial biogenesis in
      vascular endothelium.
AB  - OBJECTIVE: Enhancing structural and functional integrity of mitochondria is an
      emerging therapeutic option against endothelial dysfunction. In this study, we
      sought to investigate the effect of fluid shear stress on mitochondrial
      biogenesis and mitochondrial respiratory function in endothelial cells (ECs)
      using in vitro and in vivo complementary studies. METHODS AND RESULTS: Human
      aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20
      dyne/cm2) for various durations using a cone-and-plate shear apparatus. We
      observed significant increases in the expression of key genes related to
      mitochondrial biogenesis and mitochondrial quality control as well as mtDNA
      content and mitochondrial mass under the shear stress conditions. Mitochondrial
      respiratory function was enhanced when cells were intermittently exposed to
      laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished
      glycolysis and decreased mitochondrial membrane potential (DeltaPsim). Likewise,
      in in vivo experiments, mice that were subjected to a voluntary wheel running
      exercise for 5 weeks showed significantly higher mitochondrial content determined
      by en face staining in the conduit (greater and lesser curvature of the aortic
      arch and thoracic aorta) and muscle feed (femoral artery) arteries compared to
      the sedentary control mice. Interestingly, however, the mitochondrial biogenesis
      was not observed in the mesenteric artery. This region-specific adaptation is
      likely due to the differential blood flow redistribution during exercise in the
      different vessel beds. CONCLUSION: Taken together, our findings suggest that
      exercise enhances mitochondrial biogenesis in vascular endothelium through a
      shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial
      pathway by which a chronic exercise may be beneficial for vascular function.

PMID- 25375174
TI  - A functional portrait of Med7 and the mediator complex in Candida albicans.
AB  - Mediator is a multi-subunit protein complex that regulates gene expression in
      eukaryotes by integrating physiological and developmental signals and
      transmitting them to the general RNA polymerase II machinery. We examined, in the
      fungal pathogen Candida albicans, a set of conditional alleles of genes encoding
      Mediator subunits of the head, middle, and tail modules that were found to be
      essential in the related ascomycete Saccharomyces cerevisiae. Intriguingly, while
      the Med4, 8, 10, 11, 14, 17, 21 and 22 subunits were essential in both fungi, the
      structurally highly conserved Med7 subunit was apparently non-essential in C.
      albicans. While loss of CaMed7 did not lead to loss of viability under normal
      growth conditions, it dramatically influenced the pathogen's ability to grow in
      different carbon sources, to form hyphae and biofilms, and to colonize the
      gastrointestinal tracts of mice. We used epitope tagging and location profiling
      of the Med7 subunit to examine the distribution of the DNA sites bound by
      Mediator during growth in either the yeast or the hyphal form, two distinct
      morphologies characterized by different transcription profiles. We observed a
      core set of 200 genes bound by Med7 under both conditions; this core set is
      expanded moderately during yeast growth, but is expanded considerably during
      hyphal growth, supporting the idea that Mediator binding correlates with changes
      in transcriptional activity and that this binding is condition specific. Med7
      bound not only in the promoter regions of active genes but also within coding
      regions and at the 3' ends of genes. By combining genome-wide location profiling,
      expression analyses and phenotyping, we have identified different Med7p
      influenced regulons including genes related to glycolysis and the Filamentous
      Growth Regulator family. In the absence of Med7, the ribosomal regulon is de
      repressed, suggesting Med7 is involved in central aspects of growth control. 

PMID- 25375176
TI  - Monitoring urban greenness dynamics using multiple endmember spectral mixture
      analysis.
AB  - Urban greenness is increasingly recognized as an essential constituent of the
      urban environment and can provide a range of services and enhance residents'
      quality of life. Understanding the pattern of urban greenness and exploring its
      spatiotemporal dynamics would contribute valuable information for urban planning.
      In this paper, we investigated the pattern of urban greenness in Hangzhou, China,
      over the past two decades using time series Landsat-5 TM data obtained in 1990,
      2002, and 2010. Multiple endmember spectral mixture analysis was used to derive
      vegetation cover fractions at the subpixel level. An RGB-vegetation fraction
      model, change intensity analysis and the concentric technique were integrated to
      reveal the detailed, spatial characteristics and the overall pattern of change in
      the vegetation cover fraction. Our results demonstrated the ability of multiple
      endmember spectral mixture analysis to accurately model the vegetation cover
      fraction in pixels despite the complex spectral confusion of different land cover
      types. The integration of multiple techniques revealed various changing patterns
      in urban greenness in this region. The overall vegetation cover has exhibited a
      drastic decrease over the past two decades, while no significant change occurred
      in the scenic spots that were studied. Meanwhile, a remarkable recovery of
      greenness was observed in the existing urban area. The increasing coverage of
      small green patches has played a vital role in the recovery of urban greenness.
      These changing patterns were more obvious during the period from 2002 to 2010
      than from 1990 to 2002, and they revealed the combined effects of rapid
      urbanization and greening policies. This work demonstrates the usefulness of time
      series of vegetation cover fractions for conducting accurate and in-depth studies
      of the long-term trajectories of urban greenness to obtain meaningful information
      for sustainable urban development. 

PMID- 25375178
TI  - Blank corrections for ramped pyrolysis radiocarbon dating of sedimentary and soil
      organic carbon.
AB  - Ramped pyrolysis (RP) targets distinct components of soil and sedimentary organic
      carbon based on their thermochemical stabilities and allows the determination of
      the full spectrum of radiocarbon ((14)C) ages present in a soil or sediment
      sample. Extending the method into realms where more precise ages are needed or
      where smaller samples need to be measured involves better understanding of the
      blank contamination associated with the method. Here, we use a compiled data set
      of RP measurements of samples of known age to evaluate the mass of the carbon
      blank and its associated (14)C signature, and to assess the performance of the RP
      system. We estimate blank contamination during RP using two methods, the modern
      dead and the isotope dilution method. Our results indicate that during one
      complete RP run samples are contaminated by 8.8 +/- 4.4 MUg (time-dependent) of
      modern carbon (MC, fM ~ 1) and 4.1 +/- 5.5 MUg (time-independent) of dead carbon
      (DC, fM ~ 0). We find that the modern-dead method provides more accurate
      estimates of uncertainties in blank contamination; therefore, the isotope
      dilution method should be used with caution when the variability of the blank is
      high. Additionally, we show that RP can routinely produce accurate (14)C dates
      with precisions ~100 (14)C years for materials deposited in the last 10,000 years
      and ~300 (14)C years for carbon with (14)C ages of up to 20,000 years.

PMID- 25375177
TI  - Novel matrix proteins of Pteria penguin pearl oyster shell nacre homologous to
      the jacalin-related beta-prism fold lectins.
AB  - Nacreous layers of pearl oyster are one of the major functional biominerals. By
      participating in organic compound-crystal interactions, they assemble into
      consecutive mineral lamellae-like photonic crystals. Their biomineralization
      mechanisms are controlled by macromolecules; however, they are largely unknown.
      Here, we report two novel lectins termed PPL2A and PPL2B, which were isolated
      from the mantle and the secreted fluid of Pteria penguin oyster. PPL2A is a
      hetero-dimer composed of alpha and gamma subunits, and PPL2B is a homo-dimer of
      beta subunit, all of which surprisingly shared sequence homology with the jacalin
      related plant lectin. On the basis of knockdown experiments at the larval stage,
      the identification of PPLs in the shell matrix, and in vitro CaCO3
      crystallization analysis, we conclude that two novel jacalin-related lectins
      participate in the biomineralization of P. penguin nacre as matrix proteins.
      Furthermore, it was found that trehalose, which is specific recognizing
      carbohydrates for PPL2A and is abundant in the secreted fluid of P. penguin
      mantle, functions as a regulatory factor for biomineralization via PPL2A. These
      observations highlight the unique functions, diversity and molecular evolution of
      this lectin family involved in the mollusk shell formation. 

PMID- 25375179
TI  - Comparative genomic analysis of slc39a12/ZIP12: insight into a zinc transporter
      required for vertebrate nervous system development.
AB  - The zinc transporter ZIP12, which is encoded by the gene slc39a12, has previously
      been shown to be important for neuronal differentiation in mouse Neuro-2a
      neuroblastoma cells and primary mouse neurons and necessary for neurulation
      during Xenopus tropicalis embryogenesis. However, relatively little is known
      about the biochemical properties, cellular regulation, or the physiological role
      of this gene. The hypothesis that ZIP12 is a zinc transporter important for
      nervous system function and development guided a comparative genetics approach to
      uncover the presence of ZIP12 in various genomes and identify conserved sequences
      and expression patterns associated with ZIP12. Ortholog detection of slc39a12 was
      conducted with reciprocal BLAST hits with the amino acid sequence of human ZIP12
      in comparison to the human paralog ZIP4 and conserved local synteny between
      genomes. ZIP12 is present in the genomes of almost all vertebrates examined, from
      humans and other mammals to most teleost fish. However, ZIP12 appears to be
      absent from the zebrafish genome. The discrimination of ZIP12 compared to ZIP4
      was unsuccessful or inconclusive in other invertebrate chordates and
      deuterostomes. Splice variation, due to the inclusion or exclusion of a conserved
      exon, is present in humans, rats, and cows and likely has biological
      significance. ZIP12 also possesses many putative di-leucine and tyrosine motifs
      often associated with intracellular trafficking, which may control cellular zinc
      uptake activity through the localization of ZIP12 within the cell. These findings
      highlight multiple aspects of ZIP12 at the biochemical, cellular, and
      physiological levels with likely biological significance. ZIP12 appears to have
      conserved function as a zinc uptake transporter in vertebrate nervous system
      development. Consequently, the role of ZIP12 may be an important link to reported
      congenital malformations in numerous animal models and humans that are caused by
      zinc deficiency. 

PMID- 25375180
TI  - Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT
      signaling in the Drosophila testis.
AB  - Stem cells in tissues reside in and receive signals from local microenvironments
      called niches. Understanding how multiple signals within niches integrate to
      control stem cell function is challenging. The Drosophila testis stem cell niche
      consists of somatic hub cells that maintain both germline stem cells and somatic
      cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit
      Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically
      in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in
      order for them to compete for occupancy in the niche. CySCs also require the Slit
      Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to
      the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche
      occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of
      adherens junction components, suggesting that the two work together to balance
      CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT
      signaling, an important maintenance pathway for both germline and cyst stem cells
      in the testis. Our work indicates that Slit-Robo signaling affects stem cell
      function downstream of the JAK-STAT pathway by controlling the ability of stem
      cells to compete for occupancy in their niche. 

PMID- 25375182
TI  - Coastal acidification induced by tidal-driven submarine groundwater discharge in
      a coastal coral reef system.
AB  - We identified a barely noticed contributor, submarine groundwater discharge
      (SGD), to acidification of a coastal fringing reef system in Sanya Bay in the
      South China Sea based on time-series observations of Ra isotopes and carbonate
      system parameters. This coastal system was characterized by strong diel changes
      throughout the spring to neap tidal cycle of dissolved inorganic carbon (DIC),
      total alkalinity, partial pressure of CO2 (pCO2) and pH, in the ranges of 1851
      2131 MUmol kg(-1), 2182-2271 MUmol kg(-1), 290-888 MUatm and 7.72-8.15,
      respectively. Interestingly, the diurnal amplitudes of these parameters decreased
      from spring to neap tides, governed by both tidal pumping and biological
      activities. In ebb stages during the spring tide, we observed the lowest
      salinities along with the highest DIC, pCO2 and Ra isotopes, and the lowest pH
      and aragonite saturation state. These observations were consistent with a
      concurrent SGD rate up to 25 and 44 cm d(-1), quantified using Darcy's law and
      (226)Ra, during the spring tide ebb, but negligible at flood tides. Such tidal
      driven SGD of low pH waters is another significant contributor to coastal
      acidification, posing additional stress on coastal coral systems, which would be
      even more susceptible in future scenarios under higher atmospheric CO2. 

PMID- 25375181
TI  - The Porphyromonas gingivalis ferric uptake regulator orthologue binds hemin and
      regulates hemin-responsive biofilm development.
AB  - Porphyromonas gingivalis is a Gram-negative pathogen associated with the biofilm
      mediated disease chronic periodontitis. P. gingivalis biofilm formation is
      dependent on environmental heme for which P. gingivalis has an obligate
      requirement as it is unable to synthesize protoporphyrin IX de novo, hence P.
      gingivalis transports iron and heme liberated from the human host. Homeostasis of
      a variety of transition metal ions is often mediated in Gram-negative bacteria at
      the transcriptional level by members of the Ferric Uptake Regulator (Fur)
      superfamily. P. gingivalis has a single predicted Fur superfamily orthologue
      which we have designated Har (heme associated regulator). Recombinant Har formed
      dimers in the presence of Zn2+ and bound one hemin molecule per monomer with high
      affinity (Kd of 0.23 uM). The binding of hemin resulted in conformational changes
      of Zn(II)Har and residue 97Cys was involved in hemin binding as part of a
      predicted -97C-98P-99L- hemin binding motif. The expression of 35 genes was down
      regulated and 9 up-regulated in a Har mutant (ECR455) relative to wild-type.
      Twenty six of the down-regulated genes were previously found to be up-regulated
      in P. gingivalis grown as a biofilm and 11 were up-regulated under hemin
      limitation. A truncated Zn(II)Har bound the promoter region of dnaA (PGN_0001),
      one of the up-regulated genes in the ECR455 mutant. This binding decreased as
      hemin concentration increased which was consistent with gene expression being
      regulated by hemin availability. ECR455 formed significantly less biofilm than
      the wild-type and unlike wild-type biofilm formation was independent of hemin
      availability. P. gingivalis possesses a hemin-binding Fur orthologue that
      regulates hemin-dependent biofilm formation. 

PMID- 25375183
TI  - Herpes simplex virus-2 genital tract shedding is not predictable over months or
      years in infected persons.
AB  - Herpes simplex virus-2 (HSV-2) is a chronic reactivating infection that leads to
      recurrent shedding episodes in the genital tract. A minority of episodes are
      prolonged, and associated with development of painful ulcers. However, currently,
      available tools poorly predict viral trajectories and timing of reactivations in
      infected individuals. We employed principal components analysis (PCA) and
      singular value decomposition (SVD) to interpret HSV-2 genital tract shedding time
      series data, as well as simulation output from a stochastic spatial mathematical
      model. Empirical and model-derived, time-series data gathered over >30 days
      consists of multiple complex episodes that could not be reduced to a manageable
      number of descriptive features with PCA and SVD. However, single HSV-2 shedding
      episodes, even those with prolonged duration and complex morphologies consisting
      of multiple erratic peaks, were consistently described using a maximum of four
      dominant features. Modeled and clinical episodes had equivalent distributions of
      dominant features, implying similar dynamics in real and simulated episodes. We
      applied linear discriminant analysis (LDA) to simulation output and identified
      that local immune cell density at the viral reactivation site had a predictive
      effect on episode duration, though longer term shedding suggested chaotic
      dynamics and could not be predicted based on spatial patterns of immune cell
      density. These findings suggest that HSV-2 shedding patterns within an individual
      are impossible to predict over weeks or months, and that even highly complex
      single HSV-2 episodes can only be partially predicted based on spatial
      distribution of immune cell density. 

PMID- 25375185
TI  - General cognition predicts post-stroke recovery defined through minimal
      clinically important difference (MCID): a cohort study in an Italian
      rehabilitation clinic.
AB  - BACKGROUND: In the field of rehabilitation it is crucial to define if changes in
      functional scores correspond to relevant clinical improvements. AIM: To assess
      whether cognition affects motor recovery in post-stroke patients using a clinical
      meaningful criterion: the minimal clinically important difference (MCID). DESIGN:
      Retrospective cohort study. SETTING: Inpatient rehabilitation clinic POPULATION:
      Two hundred nine first-ever stroke patients undergoing a post-acute inpatient
      rehabilitation. METHODS: Cognitive status was assessed with the cognitive FIM and
      the Mini-Mental State Examination (MMSE). The response to the rehabilitation was
      defined as the achievement of the MCID between admission and discharge in the
      motor FIM (responder) and both in the motor and in the cognitive FIM (best
      responder). RESULTS: Subjects with a baseline higher MMSE>24.9 had a near four
      fold higher probability of being responder (OR 3.91; 95% CI 1.72-8.89) and a two
      fold higher probability of being best-responder (OR 2.69; 95% CI 1.24-5.84) on
      motor FIM as compared to those with a MMSE<=24.9. A duration of the
      rehabilitation of 55-61 days implies a three-fold higher probability (OR 3.17;
      95% CI 1.15-8.72) to be responder as compared to shorter period of treatment; a
      treatment >61 days does not involve a greater probability of response.
      CONCLUSIONS: This is the first study that examined post-stroke motor recovery
      mainly in terms of clinical relevance (MCID). Subjects with a higher cognitive
      level are more likely to achieve a clinically meaningful recovery. CLINICAL
      REHABILITATION IMPACT: MCID can be applied extensively to post-stroke patients
      undergoing to an inpatient rehabilitation in order to have a clinically useful
      instrument that assess the recovery.

PMID- 25375184
TI  - Host-specific parvovirus evolution in nature is recapitulated by in vitro
      adaptation to different carnivore species.
AB  - Canine parvovirus (CPV) emerged as a new pandemic pathogen of dogs in the 1970s
      and is closely related to feline panleukopenia virus (FPV), a parvovirus of cats
      and related carnivores. Although both viruses have wide host ranges, analysis of
      viral sequences recovered from different wild carnivore species, as shown here,
      demonstrated that>95% were derived from CPV-like viruses, suggesting that CPV is
      dominant in sylvatic cycles. Many viral sequences showed host-specific mutations
      in their capsid proteins, which were often close to sites known to control
      binding to the transferrin receptor (TfR), the host receptor for these carnivore
      parvoviruses, and which exhibited frequent parallel evolution. To further examine
      the process of host adaptation, we passaged parvoviruses with alternative
      backgrounds in cells from different carnivore hosts. Specific mutations were
      selected in several viruses and these differed depending on both the background
      of the virus and the host cells in which they were passaged. Strikingly, these in
      vitro mutations recapitulated many specific changes seen in viruses from natural
      populations, strongly suggesting they are host adaptive, and which were shown to
      result in fitness advantages over their parental virus. Comparison of the
      sequences of the transferrin receptors of the different carnivore species
      demonstrated that many mutations occurred in and around the apical domain where
      the virus binds, indicating that viral variants were likely selected through
      their fit to receptor structures. Some of the viruses accumulated high levels of
      variation upon passage in alternative hosts, while others could infect multiple
      different hosts with no or only a few additional mutations. Overall, these
      studies demonstrate that the evolutionary history of a virus, including how long
      it has been circulating and in which hosts, as well as its phylogenetic
      background, has a profound effect on determining viral host range. 

PMID- 25375186
TI  - Spasticity in disorders of consciousness: a behavioral study.
AB  - BACKGROUND: Spasticity is a frequent complication after severe brain injury,
      which may impede the rehabilitation process and diminish the patients' quality of
      life. AIM: We here investigate the presence of spasticity in a population of non
      communicative patients with disorders of consciousness. We also evaluate the
      correlation between spasticity and potential factors of co-morbidity, frequency
      of physical therapy, time since insult, presence of pain, presence of tendon
      retraction, etiology and diagnosis. DESIGN: Cross-sectional study. SETTING:
      University Hospital of Liege, Belgium. POPULATION: Sixty-five patients with
      chronic (>3 months post insult) disorders of consciousness were included (22
      women; mean age: 44+/-14 y; 40 with traumatic etiology; 40 in a minimally
      conscious state; time since insult: 39+/-37 months). METHODS: Spasticity was
      measured with the Modified Ashworth Scale (MAS) and pain was assessed using the
      Nociception Coma Scale-Revised (NCS-R). RESULTS: Out of 65 patients, 58
      demonstrated signs of spasticity (89%; MAS>=1), including 40 who showed severe
      spasticity (61.5%; MAS>=3). Patients with spasticity receiving anti-spastic
      medication were more spastic than unmedicated patients. A negative correlation
      was observed between the severity of spasticity and the frequency of physical
      therapy. MAS scores correlated positively with time since injury and NCS-R
      scores. We did not observe a difference of spasticity between the diagnoses.
      CONCLUSION: A large proportion of patients with disorders of consciousness
      develop severe spasticity, possibly affecting their functional recovery and their
      quality of life. The observed correlation between degrees of spasticity and pain
      scores highlights the importance of pain management in these patients with
      altered states of consciousness. Finally, the relationship between spasticity and
      treatment (i.e., pharmacological and physical therapy) should be further
      investigated in order to improve clinical care. CLINICAL REHABILITATION IMPACT:
      Managing spasticity at first signs could improve rehabilitation of patients with
      disorders of consciousness and maximize their chances of recovery. In addition,
      decreasing this trouble could allow a better quality of life for these non
      communicative patients.

PMID- 25375188
TI  - Cytotoxic sesterterpenoids isolated from the marine sponge Scalarispongia sp.
AB  - Eight scalarane sesterterpenoids, including four new compounds, were isolated
      from the marine sponge Scalarispongia sp. The structures of the new compounds
      were elucidated by 2D-NMR and HRMS analyses. All of the isolated compounds, with
      the exception of 16-O-deacetyl-12,16-epi-scalarolbutanolide, showed significant
      in vitro cytotoxicity (GI50 values down to 5.2 MUM) against six human cancer cell
      lines. 

PMID- 25375187
TI  - Effects of Bofu-Tsusho-San on diabetes and hyperlipidemia associated with AMP
      activated protein kinase and glucose transporter 4 in high-fat-fed mice.
AB  - This study was undertaken to examine the effect and mechanism of Bofu-tsusho-san
      formula (BO) on hyperglycemia and hyperlipidemia and in mice fed with a high-fat
      (HF) diet. The C57BL/6J mice were received control/HF diet for 12 weeks, and oral
      administration of BO (at three doses) or rosiglitazone (Rosi) or vehicle for the
      last 4 weeks. Blood, skeletal muscle and tissues were examined by means of
      measuring glycaemia and dyslipidaemia-associated events. BO treatment effectively
      prevented HF diet-induced increases in the levels of triglyceride (TG), free
      fatty acid (FFA) and leptin (p<0.01, p<0.01, p<0.01, respectively). BO treatment
      exhibited reduced both visceral fat mass and hepatic triacylglycerol content;
      moreover, BO treatment displayed significantly decreased both the average area of
      the cut of adipocytes and ballooning of hepatocytes. BO treatment exerted
      increased the protein contents of glucose transporter 4 (GLUT4) in skeletal
      muscle, and caused lowered blood glucose levels. BO treatment displayed increased
      levels of phosphorylated AMP-activated protein kinase (AMPK) in both skeletal
      muscle and liver tissue. Furthermore, BO reduced the hepatic expression of
      glucose-6-phosphatase (G6Pase) and phosphenolpyruvate carboxykinase (PEPCK) and
      glucose production. Therefore, it is possible that the activation of AMPK by BO
      leads to diminished gluconeogenesis in liver tissue. BO increased hepatic
      expressions of peroxisome proliferator-activated receptor alpha (PPARalpha),
      whereas down-regulating decreasing expressions of fatty acid synthesis, including
      sterol regulatory element binding protein 1c (SREBP1c) and fatty acid synthase
      (FAS), resulting in a decrease in circulating triglycerides. This study
      originally provides the evidence that amelioration of dyslipidemic and diabetic
      state by BO in HF-fed mice occurred by regulation of GLUT4, SREBP1c, FAS,
      PPARalpha, adiponectin and AMPK phosphorylation.

PMID- 25375190
TI  - Molecular science for drug development and biomedicine.
AB  - With the avalanche of biological sequences generated in the postgenomic age,
      molecular science is facing an unprecedented challenge, i.e., how to timely
      utilize the huge amount of data to benefit human beings. Stimulated by such a
      challenge, a rapid development has taken place in molecular science, particularly
      in the areas associated with drug development and biomedicine, both experimental
      and theoretical. The current thematic issue was launched with the focus on the
      topic of "Molecular Science for Drug Development and Biomedicine", in hopes to
      further stimulate more useful techniques and findings from various approaches of
      molecular science for drug development and biomedicine.[...]. 

PMID- 25375189
TI  - Dinitrosopiperazine-mediated phosphorylated-proteins are involved in
      nasopharyngeal carcinoma metastasis.
AB  - N,N'-dinitrosopiperazine (DNP) with organ specificity for nasopharyngeal
      epithelium, is involved in nasopharyngeal carcinoma (NPC) metastasis, though its
      mechanism is unclear. To reveal the pathogenesis of DNP-induced metastasis,
      immunoprecipitation was used to identify DNP-mediated phosphoproteins. DNP
      mediated NPC cell line (6-10B) motility and invasion was confirmed. Twenty-six
      phosphoproteins were increased at least 1.5-fold following DNP exposure. Changes
      in the expression levels of selected phosphoproteins were verified by Western
      blotting analysis. DNP treatment altered the phosphorylation of ezrin (threonine
      567), vimentin (serine 55), stathmin (serine 25) and STAT3 (serine 727).
      Furthermore, it was shown that DNP-dependent metastasis is mediated in part
      through ezrin at threonine 567, as DNP-mediated metastasis was decreased when
      threonine 567 of ezrin was mutated. Strikingly, NPC metastatic tumors exhibited a
      higher expression of phosphorylated-ezrin at threonine 567 than the primary
      tumors. These findings provide novel insight into DNP-induced NPC metastasis and
      may contribute to a better understanding of the metastatic mechanisms of NPC
      tumors. 

PMID- 25375191
TI  - Role of NADPH oxidase and xanthine oxidase in mediating inducible VT/VF and
      triggered activity in a canine model of myocardial ischemia.
AB  - BACKGROUND: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due
      to triggered activity (TA) from delayed afterdepolarizations (DADs) is
      reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and
      TA can be blocked by reducing reactive oxygen species (ROS). We tested the
      hypothesis that inhibition of NADPH oxidase and xanthine oxidase would block
      VT/VF. METHODS: 69 dogs received apocynin (APO), 4 mg/kg intraveneously (IV),
      oxypurinol (OXY), 4 mg/kg IV, or both APO and OXY (BOTH) agents, or saline 3 h
      after coronary occlusion. Endocardium from ischemic sites (3-D mapping) was
      sampled for Rac1 (GTP-binding protein in membrane NADPH oxidase) activation or
      standard microelectrode techniques. Results (mean+/-SE, * p<0.05): VT/VF
      originating from ischemic zones was blocked by APO in 6/10 *, OXY in 4/9 *, BOTH
      in 5/8 * or saline in 1/27; 11/16 VT/VFs blocked were focal. In isolated
      myocardium, TA was blocked by APO (10(-6) M) or OXY (10(-8) M). Rac1 levels in
      ischemic endocardium were decreased by APO or OXY. CONCLUSION: APO and OXY
      suppressed focal VT/VF due to DADs, but the combination of the drugs was not more
      effective than either alone. Both drugs inhibited ischemic Rac1 with inhibition
      by OXY suggesting ROS-induced ROS. The inability to totally prevent VT/VF
      suggests that other mechanisms also contribute to ischemic VT.

PMID- 25375193
TI  - Localized electric field of plasmonic nanoplatform enhanced photodynamic tumor
      therapy.
AB  - Near-infrared plasmonic nanoparticles demonstrate great potential in disease
      theranostic applications. Herein a nanoplatform, composed of mesoporous silica
      coated gold nanorods (AuNRs), is tailor-designed to optimize the photodynamic
      therapy (PDT) for tumor based on the plasmonic effect. The surface plasmon
      resonance of AuNRs was fine-tuned to overlap with the exciton absorption of
      indocyanine green (ICG), a near-infrared photodynamic dye with poor
      photostability and low quantum yield. Such overlap greatly increases the singlet
      oxygen yield of incorporated ICG by maximizing the local field enhancement, and
      protecting the ICG molecules against photodegradation by virtue of the high
      absorption cross section of the AuNRs. The silica shell strongly increased ICG
      payload with the additional benefit of enhancing ICG photostability by
      facilitating the formation of ICG aggregates. As-fabricated AuNR@SiO2-ICG
      nanoplatform enables trimodal imaging, near-infrared fluorescence from ICG, and
      two-photon luminescence/photoacoustic tomography from the AuNRs. The integrated
      strategy significantly improved photodynamic destruction of breast tumor cells
      and inhibited the growth of orthotopic breast tumors in mice, with mild laser
      irradiation, through a synergistic effect of PDT and photothermal therapy. Our
      study highlights the effect of local field enhancement in PDT and demonstrates
      the importance of systematic design of nanoplatform to greatly enhancing the
      antitumor efficacy. 

PMID- 25375192
TI  - Overexpression of the CaTIP1-1 pepper gene in tobacco enhances resistance to
      osmotic stresses.
AB  - Both the gene expression and activity of water channel protein can control
      transmembrane water movement. We have reported the overexpression of CaTIP1-1,
      which caused a decrease in chilling tolerance in transgenic plants by increasing
      the size of the stomatal pore. CaTIP1-1 expression was strongly induced by salt
      and mannitol stresses in pepper (Capsicum annuum). However, its biochemical and
      physiological functions are still unknown in transgenic tobacco. In this study,
      transient expression of CaTIP1-1-GFP in tobacco suspension cells revealed that
      the protein was localized in the tonoplast. CaTIP1-1 overexpressed in radicle
      exhibited vigorous growth under high salt and mannitol treatments more than wild
      type plants. The overexpression of CaTIP1-1 pepper gene in tobacco enhanced the
      antioxidant enzyme activities and increased transcription levels of reactive
      oxygen species-related gene expression under osmotic stresses. Moreover, the
      viability of transgenic tobacco cells was higher than the wild-type after
      exposure to stress. The pepper plants with silenced CaTIP1-1 in P70 decreased
      tolerance to salt and osmotic stresses using the detached leaf method. We
      concluded that the CaTIP1-1 gene plays an important role in response to osmotic
      stresses in tobacco. 

PMID- 25375194
TI  - Human milk and breastfeeding outcomes in infants with congenital heart disease.
AB  - BACKGROUND: Although human milk (HM) is the recommended form of infant nutrition,
      the provision of HM feeding among infants with congenital heart disease in the
      cardiac intensive care unit is unknown. Therefore the aim of the study was to
      understand the prevalence of pumping initiation, HM feeding, and breastfeeding
      patterns of mothers and their infants born with congenital heart disease.
      SUBJECTS AND METHODS: This was a prospective cohort study conducted a large
      children's hospital with a cardiac referral program and unit. All women with
      infants with congenital heart disease were approached for enrollment in order to
      document HM prevalence. RESULTS: The majority of women (89%) initiated lactation
      via pumping for their infants. On average, mothers pumped five to six times per
      day, and mothers were able to achieve a milk supply of over 500 mL/day. Once
      infants received enteral feeds, over 70% of the infant diet was HM. Very few
      (13%) infants fed via direct breastfeedings; rather, they received HM via gavage
      or bottle. There was a significant difference in pumping initiation based on
      where the infant was born, with mothers delivering in the hospital having a
      significantly higher pumping initiation rate (96% born in this hospital, 67% born
      in an outside hospital). CONCLUSIONS: Mothers who have infants diagnosed with
      congenital heart disease should be encouraged to initiate pumping for their
      infants. Future research is warranted regarding the dose response of HM and
      specific health outcomes and the need for postdischarge services for these
      families.

PMID- 25375195
TI  - Bifunctional nanocatalyst based on three-dimensional carbon nanotube-graphene
      hydrogel supported Pd nanoparticles: one-pot synthesis and its catalytic
      properties.
AB  - We reported the development of a new type of bifunctional nanocatalyst based on
      three-dimensional (3D) macroscopic carbon nanotube (CNT)-graphene hydrogel (GH)
      supported Pd nanoparticles (i.e., Pd-CNT-GH) and explored its practical
      application in catalytic reduction of p-nitrophenol to p-aminophenol. The 3D Pd
      CNT-GH was synthesized by a facile one-pot self-assembled approach through
      hydrothermal treatment of a mixed aqueous precursor solution of PdCl4(2-), CNT,
      and graphene oxide (GO). Under the appropriate condition, the spontaneous redox
      reaction between precursor PdCl4(2-) and CNT-GO as well as the self-assembly of
      macroscopic CNT-GH occurs simultaneously, leading to the formation of 3D Pd-CNT
      GH. Because of the unique structural and functional properties of different
      components in the nanocatalyst and the synergistic effect between them, the as
      prepared Pd-CNT-GH exhibits superior catalytic performance toward the reduction
      of p-nitrophenol to p-aminophenol, with 100% conversion within 30 s, even when
      the content of Pd in it is as low as 2.98 wt %. Moreover, after 20 successive
      cycles of reactions, the reaction time still keeps within 46 s. Therefore, the
      rational design of 3D macroscopic graphene-based nanohybrid material supported
      highly catalytically active nanoparticles, combined with the facile one-pot self
      assembled strategy, provide a universal platform to fabricate desired 3D
      multifunctional nanomaterials that can be used in a broad range of catalysis,
      environmental protection, energy storage and conversation, drug delivery,
      chemical and biological sensing, and so forth. 

PMID- 25375196
TI  - Carotid space mass.

PMID- 25375197
TI  - Multistimuli-responsive azobenzene nanofibers with aggregation-induced emission
      enhancement characteristics.
AB  - A new azobenzene-based chromophore was synthesized to create one-dimensional (1D)
      nanofibers with aggregation-induced emission enhancement characteristics. The
      enhanced red fluorescence of the fibrous structures can be switched off via
      mechanical pressure, friction, or heat by pressing, rubbing, or annealing. 

PMID- 25375199
TI  - Fluorescent carbon nanoparticles derived from natural materials of mango fruit
      for bio-imaging probes.
AB  - Water soluble fluorescent carbon nanoparticles (FCP) obtained from a single
      natural source, mango fruit, were developed as unique materials for non-toxic bio
      imaging with different colors and particle sizes. The prepared FCPs showed blue
      (FCP-B), green (FCP-G) and yellow (FCP-Y) fluorescence, derived by the controlled
      carbonization method. The FCPs demonstrated hydrodynamic diameters of 5-15 nm,
      holding great promise for clinical applications. The biocompatible FCPs
      demonstrated great potential in biological fields through the results of in vitro
      imaging and in vivo biodistribution. Using intravenously administered FCPs with
      different colored particles, we precisely defined the clearance and
      biodistribution, showing rapid and efficient urinary excretion for safe
      elimination from the body. These findings therefore suggest the promising
      possibility of using natural sources for producing fluorescent materials. 

PMID- 25375198
TI  - Delayed administration of alpha-difluoromethylornithine prevents hippocampus
      dependent cognitive impairment after single and combined injury in mice.
AB  - Radiation exposure due to radiological terrorism and military circumstances are a
      continuing threat for the civilian population. In an uncontrolled radiation
      event, it is likely that there will be other types of injury involved, including
      trauma. While radiation combined injury is recognized as an area of great
      significance, overall there is a paucity of information regarding the mechanisms
      underlying the interactions between irradiation and other forms of injury, or
      what countermeasures might be effective in ameliorating such changes. The
      objective of this study was to determine if difluoromethylornithine (DFMO) could
      reduce the adverse effects of single or combined injury if administered beginning
      24 h after exposure. Eight-week-old C57BL/J6 young-adult male mice received whole
      body cesium-137 ((137)Cs) irradiation with 4 Gy. Immediately after irradiation,
      unilateral traumatic brain injury was induced using a controlled cortical impact
      system. Forty-four days postirradiation, animals were tested for hippocampus
      dependent cognitive performance in the Morris water maze. After cognitive
      testing, animals were euthanized and their brains snap frozen for
      immunohistochemical assessment of neuroinflammation (activated microglia) and
      neurogenesis in the hippocampal dentate gyrus. Our data show that single and
      combined injuries induced variable degrees of hippocampus-dependent cognitive
      dysfunction, and when given 24 h post trauma, DFMO treatment ameliorated those
      effects. Cellular changes including neurogenesis and numbers of activated
      microglia were generally not associated with the cognitive changes. Further
      analyses also revealed that DFMO increased hippocampal protein levels of the
      antioxidants thioredoxin 1 and peroxiredoxin 3 compared to vehicle treated
      animals. While the mechanisms responsible for the improvement in cognition after
      DFMO treatment are not yet clear, these results constitute a basis for further
      development of DFMO as a countermeasure for ameliorating the of risks for
      cognitive dysfunction in individuals subjected to trauma and radiation combined
      injury. 

PMID- 25375200
TI  - Maintaining neural stem cell identity in the brain.
AB  - In the developing fruit fly brain, a protein called Trithorax increases the
      number of neural cells produced from a single stem cell, in part by regulating
      the transcription of the target genes buttonhead and pointed. 

PMID- 25375201
TI  - NMR spectroscopy for metabolomics and metabolic profiling.

PMID- 25375202
TI  - Heterodimeric ent-kauranoids from Isodon tenuifolius.
AB  - Thirteen new heterodimeric ent-kauranoids, bistenuifolins A-M (1-13), were
      isolated from the aerial parts of Isodon tenuifolius. The constituent units of
      compounds 1-6 were linked by a six-membered dihydropyran ring, while those of
      compounds 7-11 were joined by a rare single carbon-carbon bond (C-16->C-17'). The
      constituent units of 12 and 13 were linked via an unusual cyclobutane moiety. The
      structures of these metabolites were established via spectrometric analyses, and
      the absolute configurations of 1 and 4 were defined by single-crystal X-ray
      diffraction. Selected compounds were evaluated for their cytotoxicity against a
      small panel of human tumor cell lines; bistenuifolin B (2) exhibited weak
      inhibitory effects. 

PMID- 25375203
TI  - Differential beta2-adrenergic receptor expression defines the phenotype of non
      tumorigenic and malignant human breast cell lines.
AB  - Breast cancer is the most frequent malignancy in women. Several reports
      demonstrated that adrenergic receptors (ARs) are involved in breast cancer. Here
      we observed that epinephrine (Epi), an endogenous AR agonist, caused opposite
      effects in non-tumorigenic (MCF-10A and HBL-100) and tumor cells (MCF-7 and MDA
      MB-231). Thus, Epi, in non-tumor breast cells, as well as isoproterenol (beta
      agonist), in all cell lines, maintained a benign phenotype, decreasing cell
      proliferation and migration, and stimulating cell adhesion. beta-AR expression
      and cAMP levels were higher in MCF-10A than in MCF-7 cells. beta2-AR knock-down
      caused a significant increase of cell proliferation and migration, and a decrease
      of cell adhesion both in basal and in Iso-stimulated conditions. Coincidently,
      beta2-AR over-expression induced a significant decrease of cell proliferation and
      migration, and an increase of cell adhesion. Therefore, beta2-AR is implied in
      cell phenotype and its agonists or antagonists could eventually complement cancer
      therapy.

PMID- 25375206
TI  - Ormocomp-modified glass increases collagen binding and promotes the adherence and
      maturation of human embryonic stem cell-derived retinal pigment epithelial cells.
AB  - In in vitro live-cell imaging, it would be beneficial to grow and assess human
      embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells on thin,
      transparent, rigid surfaces such as cover glasses. In this study, we assessed how
      the silanization of glass with 3-aminopropyltriethoxysilane (APTES), 3
      (trimethoxysilyl)propyl methacrylate (MAPTMS), or polymer-ceramic material
      Ormocomp affects the surface properties, protein binding, and maturation of hESC
      RPE cells. The surface properties were studied by contact angle measurements, X
      ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and a
      protein binding assay. The cell adherence and proliferation were evaluated by
      culturing hESCRPE cells on collagen IV-coated untreated or silanized surfaces for
      42 days. The Ormocomp treatment significantly increased the hydrophobicity and
      roughness of glass surfaces compared to the APTES and MAPTMS treatments. The XPS
      results indicated that the Ormocomp treatment changes the chemical composition of
      the glass surface by increasing the carbon content and the number of C-O/?O
      bonds. The protein-binding test confirmed that the Ormocomp-treated surfaces
      bound more collagen IV than did APTES- or MAPTMS-treated surfaces. All of the
      silane treatments increased the number of cells: after 42 days of culture,
      Ormocomp had 0.38, APTES had 0.16, MAPTMS had 0.19, and untreated glass had only
      0.062, all presented as million cells cm(-2). There were no differences in cell
      numbers compared to smoother to rougher Ormocomp surfaces, suggesting that the
      surface chemistry and, more specifically, the collagen binding in combination
      with Ormocomp are beneficial to hESC-RPE cell culture. This study clearly
      demonstrates that Ormocomp treatment combined with collagen coating significantly
      increases hESC-RPE cell attachment compared to commonly used silanizing agents
      APTES and MAPTMS. Ormocomp silanization could thus enable the use of microscopic
      live cell imaging methods for hESC-RPE cells. 

PMID- 25375204
TI  - How mRNA is misspliced in acute myelogenous leukemia (AML)?
AB  - Approximately one-third of expressed genes are misspliced in AML, opening the
      possibility that additional factors than splicing factor mutations might cause
      RNA missplicing in these diseases. AML cells harbor a constellation of epigenetic
      modifications and regularly express large amounts of WT1 transcripts. Histone
      acetylation/methylation and DNA CpG methylation favor either exon skipping or
      inclusion, mainly through interfering with RNA Pol II-mediated elongation. This
      can result either from the binding of various factors on Pol II or alternatively
      from the recruitment of DNA binding factors that create roadblocks to Pol II
      induced elongation. WT1 exhibits pleiotropic effects on mRNA splicing, which
      mainly result from the binding properties of WT1 via its zinc fingers domains to
      DNA, RNA, and proteins. Through the repression of the kinase SRPK1, WT1 modifies
      the splicing of VEGF, which plays important roles in hematopoiesis and
      angiogenesis. At the protein level, WT1 interacts with the splicing factors
      U2AF2, WTAP, and RPM4. Therefore, AML cells appear to have acquired numerous
      properties known to interfere with mRNA splicing. The challenge is now to
      elucidate these links in order to trigger mRNA splicing at the therapeutic level.

PMID- 25375205
TI  - Prevention of diabetes-promoted colorectal cancer by (n-3) polyunsaturated fatty
      acids and (n-3) PUFA mimetic.
AB  - The global obesity / diabetes epidemic has resulted in robust increase in the
      incidence of colorectal cancer (CRC). Epidemiological, animal and human studies
      have indicated efficacy of (n-3) PUFA in chemoprevention of sporadic and genetic
      driven CRC. However, diabetes-promoted CRC presents a treatment challenge that
      surpasses that of sporadic CRC. This report analyzes the efficacy of (n-3) PUFA
      generated by the fat-1 transgene that encodes an (n-6) to (n-3) PUFA desaturase,
      and of synthetic (n-3) PUFA mimetic (MEDICA analog), to suppress CRC development
      in carcinogen-induced diabetes-promoted animal model. Carcinogen-induced CRC is
      shown here to be promoted by the diabetes context, in terms of increased aberrant
      crypt foci (ACF) load, cell proliferation and epithelial dedifferentiation, being
      accompanied by increase in the expression of HNF4alpha, beta-catenin, and beta
      catenin-responsive genes. Incorporating the fat-1 transgene in the diabetes
      context, or oral MEDICA treatment, resulted in ameliorating the diabetic
      phenotype and in abrogating CRC, with decrease in ACF load, cell proliferation
      and the expression of HNF-4alpha, beta-catenin, and beta-catenin-responsive
      genes. The specificity of (n-3) PUFA in abrogating CRC development, as contrasted
      with enhancing CRC by (n-6) PUFA, was similarly verified in CRC cell lines. These
      findings may indicate prospective therapeutic potential of (n-3) PUFA or MEDICA
      in the management of CRC, in particular diabetes-promoted CRC. 

PMID- 25375207
TI  - Influences of melatonin treatment, melatonin receptor 1A (MTNR1A) and kisspeptin
      (KiSS-1) gene polymorphisms on first conception in Sarda ewe lambs.
AB  - In order to investigate if the melatonin receptor 1A (MTNR1A) and kisspeptin
      (KiSS-1) genes influence the reproductive response to melatonin treatment, 510
      Sarda ewe lambs were divided into groups C (control) and M; Group M received one
      melatonin implant (18mg). After 35 days rams were introduced for 40 days and
      subsequent lambing dates and number of newborns were recorded. The MTNR1A gene
      Exon II and KiSS-1 gene Exon I were amplified and genotyped by restriction
      fragment length polymorphism (RFLP) and single-strand conformation polymorphism
      analysis. Two single nucleotide polymorphisms (SNPs; C606T and G612A) in MTNR1A
      and one (G1035A) in KiSS-1 were found. The most frequent genotypes were G/G (63%)
      and C/C (53%) for MTNR1A and G/G (92%) for KiSS-1. Treated animals showed a
      higher lambing rate (P<0.05) and an advanced lambing date (P<0.05) compared with
      controls. The three SNPs did not influence the onset of reproductive activity.
      The majority of the G/G animals of Group M lambed before 190 days after ram
      introduction (P<0.05), while in Group C a higher number of G/G animals lambed
      after this date. Data revealed the positive effect of melatonin treatment on the
      time of first conception in ewe lambs and highlighted that the G/G genotype of
      the MTNR1A gene is able to influence the reproductive response to melatonin
      treatment. 

PMID- 25375210
TI  - Silymarin in liposomes and ethosomes: pharmacokinetics and tissue distribution in
      free-moving rats by high-performance liquid chromatography-tandem mass
      spectrometry.
AB  - The aim of this study was to prepare silymarin formulations (silymarin entrapped
      in liposomes and ethosomes, formulations referred to as LSM and ESM,
      respectively) to improve oral bioavailability of silymarin and evaluate its
      tissue distribution by liquid chromatography with tandem mass spectrometry (LC
      MS/MS) in free-moving rats. Silibinin is the major active constituent of
      silymarin, which is the main component to be analyzed. A rapid, sensitive, and
      repeatable LC-MS/MS method was developed and validated in terms of precision,
      accuracy, and extraction recovery. Furthermore, the established method was
      applied to study the pharmacokinetics and tissue distribution of silymarin in
      rats. The size, zeta potential, and drug release of the formulations were
      characterized. These results showed that the LSM and ESM encapsulated
      formulations of silymarin may provide more efficient tissue distribution and
      increased oral bioavailability, thus improving its therapeutic bioactive
      properties in the body. 

PMID- 25375211
TI  - Epidemiology of dengue disease in Malaysia (2000-2012): a systematic literature
      review.
AB  - A literature survey and analysis was conducted to describe the epidemiology of
      dengue disease in Malaysia between 2000 and 2012. Published literature was
      searched for epidemiological studies of dengue disease, using specific search
      strategies for each electronic database; 237 relevant data sources were
      identified, 28 of which fulfilled the inclusion criteria. The epidemiology of
      dengue disease in Malaysia was characterized by a non-linear increase in the
      number of reported cases from 7,103 in 2000 to 46,171 in 2010, and a shift in the
      age range predominance from children toward adults. The overall increase in
      dengue disease was accompanied by a rise in the number, but not the proportion,
      of severe cases. The dominant circulating dengue virus serotypes changed
      continually over the decade and differed between states. Several gaps in
      epidemiological knowledge were identified; in particular, studies of regional
      differences, age-stratified seroprevalence, and hospital admissions. PROTOCOL
      REGISTRATION: PROSPERO #CRD42012002293.

PMID- 25375212
TI  - A connectivity-based eco-regionalization method of the Mediterranean Sea.
AB  - Ecoregionalization of the ocean is a necessary step for spatial management of
      marine resources. Previous ecoregionalization efforts were based either on the
      distribution of species or on the distribution of physical and biogeochemical
      properties. These approaches ignore the dispersal of species by oceanic
      circulation that can connect regions and isolates others. This dispersal effect
      can be quantified through connectivity that is the probability, or time of
      transport between distinct regions. Here a new regionalization method based on a
      connectivity approach is described and applied to the Mediterranean Sea. This
      method is based on an ensemble of Lagrangian particle numerical simulations using
      ocean model outputs at 1/12 degrees  resolution. The domain is divided into
      square subregions of 50 km size. Then particle trajectories are used to quantify
      the oceanographic distance between each subregions, here defined as the mean
      connection time. Finally the oceanographic distance matrix is used as a basis for
      a hierarchical clustering. 22 regions are retained and discussed together with a
      quantification of the stability of boundaries between regions. Identified regions
      are generally consistent with the general circulation with boundaries located
      along current jets or surrounding gyres patterns. Regions are discussed in the
      light of existing ecoregionalizations and available knowledge on plankton
      distributions. This objective method complements static regionalization
      approaches based on the environmental niche concept and can be applied to any
      oceanic region at any scale. 

PMID- 25375213
TI  - Ab initio and metadynamics studies on the role of essential functional groups in
      biomineralization of calcium carbonate and environmental situations.
AB  - The interactions of proteins, polysaccharides and other biomolecules with Ca(2+),
      CO3(2-), and water are central to the understanding of biomineralization and
      crystallization of calcium carbonate (CaCO3), and their association with the
      natural organic matter (NOM) in the environment. A molecular-level investigation
      of how such interactions and thermodynamic forces drive the nucleation and growth
      of crystalline CaCO3 in living organisms remains elusive. This paper presents ab
      initio and metadynamics studies of the interactions of Ca(2+), CO3(2-), and water
      with the essential amino acids/functional groups, e.g. arginine/NH2(+), aspartate
      or glutamate/COO(-), aspartic or glutamic acid/COOH, and serine/OH, of
      protein/organic molecules that are likely to be critical to the biomineralization
      of CaCO3. These functional groups were modeled as guanidinium (Gdm(+)), acetate
      (AcO(-)), acetic acid (AcOH), and ethanol (EtOH) molecules, respectively. The
      Gdm(+)-Ca(2+)-CO3(2-) and AcO(-)-Ca(2+)-CO3(2-) systems were found to form stable
      ion-complexes irrespective of the presence of near neighbor water molecules. The
      strong electrostatic interactions of these functional groups with their counter
      ions significantly affect the fundamental vibrational frequencies of the
      functional groups, mainly the NH2 stretching (str.) and degenerate (deg.)
      scissors modes of Gdm(+) and -C=OO, CC, and CO str. modes of AcO(-). The free
      energy calculations reveal that EtOH forms weakly bound molecular complexes with
      the Ca(2+)-CO3(2-) ion pairs in water. However, the interaction strength of EtOH
      with crystalline CaCO3 can increase significantly due to combined effect of H
      bond and electron donor acceptor (EDA) type of interactions. These results
      indicate that -NH2(+) and -COO(-) bearing molecules serve as potential nucleation
      sites promoting crystallization of CaCO3 phases while -OH bearing molecules are
      likely to control the morphology of the crystalline phases by attaching to the
      growing crystal surfaces.

PMID- 25375214
TI  - Understanding the adverse effects of ocriplasmin - reply.

PMID- 25375215
TI  - Preparation and optimization of quercetin-loaded liposomes for wound healing,
      using response surface methodology.
AB  - The basic objective of this study was to prepare quercetin-loaded liposomes by
      the thin film hydration method. The liposomal formulation was optimized using
      response surface methodology (RSM). A rotation speed of 75 rpm and a water bath
      temperature of 46 degrees C were finalized as the best for optimized drug-loaded
      liposomal formulation. In vitro characterization of the quercetin-loaded
      liposomal formulation was done through some parameters including the entrapment
      efficiency (EE), drug release (DR), and mean particle size; the resulting values
      of 86.5 +/- 0.42%, 76.5%, and146 nm were found to be standard characterized
      values respectively. It is concluded that quercetin-loaded liposomal formulations
      achieve sustained release of drug in wound areas. 

PMID- 25375216
TI  - Pea aphid biotype performance on diverse Medicago host genotypes indicates highly
      specific virulence and resistance functions.
AB  - Aphid-plant interactions depend on genotypes of both organisms, which determine
      the two-way molecular exchange that leads to compatible or incompatible outcomes.
      The underlying genes are mostly unknown, making it difficult to predict
      likelihood of aphid success or host resistance, and hampering crop genetic
      improvement. Here we screened eight pea aphid clonal genotypes collected from
      diverse legume hosts, on a species-wide panel of Medicago truncatula (Mt)
      genotypes. Aphid virulence was measured by survival, fecundity and growth rate,
      together with scores for chlorosis and necrosis as host response indicators.
      Outcomes were highly dependent on the specific aphid-host genotype combinations.
      Only one Mt line was fully resistant against all clones. Aphid-induced host
      chlorosis and necrosis varied greatly, but correlated with resistance only in a
      few combinations. Bi-clustering analysis indicated that all aphid clones could be
      distinguished by their performance profiles across the host genotypes tested,
      with each clone being genetically differentiated and potentially representing a
      distinct biotype. Clones originating from Medicago sativa ranged from highly
      virulent to almost completely avirulent on both Medicago species, indicating that
      some were well adapted, whereas others were most likely migrants. Comparisons of
      closely related pairs of Australian Mt genotypes differing in aphid resistance
      revealed no enhanced resistance to European pea aphid clones. Based on the
      extensive variation in pea aphid adaptation even on unfamiliar hosts, most likely
      reflecting multiple biotype-specific gene-for-gene interactions, we conclude that
      robust defences require an arsenal of appropriate resistance genes. 

PMID- 25375217
TI  - Associative learning for host-induced fruit volatiles in Psyttalia concolor
      (Hymenoptera: Braconidae), a koinobiont parasitoid of tephritid flies.
AB  - Parasitic wasps are fascinating organisms that rely on a wide range of
      communication channels to locate their hosts. Associative learning for foraging
      kairomones has been demonstrated for various parasitic wasps, but little is known
      for parasitoids of Tephritidae flies. Psyttalia concolor (Hymenoptera:
      Braconidae) is a koinobiont parasitoid able to attack at least 14 tephritid
      pests. Females are innately attracted by some host-induced plant volatiles
      (HIPVs), whereas others of the same bouquet are unattractive. We hypothesize that
      females may detect unattractive HIPVs in association with key resources, such as
      food and hosts, learning to respond favourably to these cues in consecutive
      experiences. We evaluated associative learning for HIPVs in P. concolor females,
      testing if they are able to associate a food reward with the presence of
      different dosages of three HIPVs, thus developing a preference for an odour
      innately unattractive. Results demonstrated that P. concolor responded favourably
      to the learned cue in consecutive experiences. For all tested HIPVs (nonanoic
      acid, decanoic acid and geranyl acetone), regardless of dosage, trained females
      preferred the reward-associated odour, whereas naive did not. Both HIPV-trained
      and naive females did not show consistent differences in latencies when choosing
      HIPVs over blank. HIPV-trained and naive wasps did not spend more time on HIPVs
      over blank. Odour learning is of adaptive importance for this generalist
      parasitoid, since it enhances host location efficiency by reducing the time
      wasted on the decision of where to search for hosts. From an applied perspective,
      these HIPVs could be used to train mass-reared P. concolor in pre-release, to
      potentially improve its efficacy in the field. 

PMID- 25375218
TI  - Influence of original host on chemotaxic behaviour and parasitism in Telenomus
      podisi Ashmead (Hymenoptera: Platygastridae).
AB  - The egg parasitoid Telenomus podisi is a natural control agent of pentatomids,
      including Euschistus heros and Tibraca limbativentris, and success of parasitism
      is dependent upon the parasitoid finding the host. We tested the influence of
      host egg volatiles and the synthetic sex pheromone (zingiberenol) of T.
      limbativentris on chemotaxic behaviour of T. podisi, as well as, the impact of
      the original host on parasitoid selection. We used mated female T. podisi (48 h
      old) that emerged from the eggs of T. limbativentris or E. heros. The bioassays
      related to chemotaxy were performed in a Y-tube olfactometer and, to parasitism
      success, in laboratory and semi-field conditions. Telenomus podisi females that
      emerged from either the stink bug eggs, chose the pheromone more than control, or
      the pheromone plus eggs of E. heros in the semi-field bioassay, led to greater
      parasitism. Females that emerged from E. heros eggs chose egg volatiles from
      their original host rather than those from T. limbativentris, while females
      emerging from T. limbativentris, chose the egg volatiles of both hosts equally.
      When T. limbativentris was the original host, T. podisi females parasitized T.
      limbativentris over E. heros, while those emerging from E. heros exclusively
      parasitized E. heros eggs. These results demonstrated that T. podisi is more
      likely to parasitize the host in which it developed and that the original host
      can exert influence on the choice by those parasitoids. Understanding how the
      factors that mediate host-parasitoid communication are interrelated can help
      biological control programmes establish more effective and reliable tools with T.
      podisi. 

PMID- 25375220
TI  - Effect of entrapped phase on the filling characteristics of closed-end nanopores.
AB  - We investigated the filling dynamics in closed-end capillaries of sub-micron
      length scale, in which the displacing phase advances at the expense of the
      entrapped phase. Contrary to common intuition, we reveal that the existence of a
      displaced phase in a closed-end nano-scale system does not necessarily retard the
      meniscus advancement over all temporal regimes, unlike what is observed in cases
      of macro-scale capillaries, but can also sometimes augment the local filling
      rates. We determined that the combined effect of surface wettability and the
      displaced phase molecules resulted from the pinning-depinning of the meniscus,
      and hence, from the local dynamics of capillary filling. We also employed a
      simple force balance-based model to capture the essential interfacial phenomena
      governing this behavior, and benchmarked the same with our molecular dynamics
      simulations. Our results suggest a possible mechanism for modifying the effective
      wettabilities of nano-scale capillaries without any modification of the surface
      architecture or chemical treatment of the surface. 

PMID- 25375219
TI  - Hypomethylation-associated up-regulation of TCF3 expression and recurrence in
      stage II and III colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Transcription factor 3 (TCF3) implicates Wnt signaling
      pathway and regulates E-cadherin expression, which is involved in aggressiveness
      of tumors. This study aims to investigate the role of TCF3 in predicting
      prognosis of patients with stage II and III colorectal cancer (CRC). METHODS:
      Real-Time quantitative PCR was performed in 64 fresh CRC tissues and 6 cell lines
      to examine TCF3 mRNA expression. TCF3 protein expression dynamics were detected
      by immunohistochemistry of 118 paraffin-embedded specimens, and the clinical
      significance of TCF3 was assessed by clinical correlation and Kaplan-Meier
      analyses. Aberrant hypomethylation of TCF3 promoter was also investigated using
      bisulfite sequencing and methylation specific PCR. RESULTS: The up-regulation of
      TCF3 mRNA was frequently detected both in CRC tissues with recurrence and
      metastasis-derived cell lines. The expression level of TCF3 protein was
      significantly correlated with histological type (P = 0.038) and disease-free
      survival time (P = 0.002). Higher TCF3 expression indicated poor prognostic
      outcomes (P<0.05, log-rank test). Multivariate analysis also showed strong TCF3
      protein expression and perineural invasion were independent adverse
      prognosticators in CRC (P = 0.010, 0.000). Moreover, it was showed that promoter
      hypomethylation of TCF3 is associated with its up-expression. CONCLUSIONS: This
      study highlighted the prognostic value of TCF3 in stage II and III CRC. The up
      regulation of TCF3, which is mainly caused by promoter hypomethylation, is one of
      the molecular mechanisms involved in the development and progression of CRC.

PMID- 25375221
TI  - Industrially benign super-compressible piezoresistive carbon foams with
      predefined wetting properties: from environmental to electrical applications.
AB  - In the present work electrically conductive, flexible, lightweight carbon sponge
      materials derived from open-pore structure melamine foams are studied and
      explored. Hydrophobic and hydrophilic surface properties - depending on the
      chosen treatment conditions - allow the separation and storage of liquid chemical
      compounds. Activation of the carbonaceous structures substantially increases the
      specific surface area from ~4 m(2)g(-1) to ~345 m(2)g(-1), while retaining the
      original three-dimensional, open-pore structure suitable for hosting, for
      example, Ni catalyst nanoparticles. In turn the structure is rendered suitable
      for hydrogenating acetone to 2-propanol and methyl isobutyl ketone as well for
      growing hierarchical carbon nanotube structures used as electric double-layer
      capacitor electrodes with specific capacitance of ~40 F/g. Mechanical stress
      strain analysis indicates the materials are super-compressible (>70% volume
      reduction) and viscoelastic with excellent damping behavior (loss of 0.69 +/-
      0.07), while piezoresistive measurements show very high gauge factors (from ~20
      to 50) over a large range of deformations. The cost-effective, robust and
      scalable synthesis - in conjunction with their fascinating multifunctional
      utility - makes the demonstrated carbon foams remarkable competitors with other
      three-dimensional carbon materials typically based on pyrolyzed biopolymers or on
      covalently bonded graphene and carbon nanotube frameworks.

PMID- 25375222
TI  - Prophylactic antibiotics for preventing pneumococcal infection in children with
      sickle cell disease.
AB  - Background This is an update of a Cochrane Review first published in 2002, and
      previously updated in 2012. People with sickle cell disease are particularly
      susceptible to infection. Infants and very young children are especially
      vulnerable, and the 'Co-operative Study of Sickle Cell Disease' observed an
      incidence rate of 10 per 100 patient years of pneumococcal septicaemia in
      children under the age of three.Vaccines, including customary pneumococcal
      vaccines, may be of limited use in this age group. Therefore, prophylactic
      penicillin regimens may be advisable for this population.Objectives To assess the
      effects of prophylactic antibiotic regimens for preventing pneumococcal infection
      in children with sickle cell disease.Search methods We searched the Cochrane
      Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register,
      which is comprised of references identified from comprehensive electronic
      database searches and handsearches of relevant journals and abstract books of
      conference proceedings.Date of the most recent search: 26 June 2014.Selection
      criteria All randomised or quasi-randomised controlled trials comparing
      prophylactic antibiotics to prevent pneumococcal infection in children with
      sickle cell disease with placebo, no treatment or a comparator drug.Data
      collection and analysis Both authors independently extracted data and assessed
      trial quality.Main results Five trials were identified by the initial search, of
      which three trials met the inclusion criteria. All of the included trials showed
      a reduced incidence of infection in children with sickle cell disease (SS or
      Sbeta0Thal) receiving prophylactic penicillin. In trials which investigated
      initiation of penicillin on risk of pneumococcal infection, the odds ratio was
      0.37 (95% CI 0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI
      0.09 to 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal
      infection were found to be relatively low in children over the age of
      five.Authors' conclusions Prophylactic penicillin significantly reduces risk of
      pneumococcal infection in children with homozygous sickle cell disease, and is
      associated with minimal adverse reactions. Further research may help to determine
      the ideal age to safely withdraw penicillin.

PMID- 25375223
TI  - Simple setup for gas-phase H/D exchange mass spectrometry coupled to electron
      transfer dissociation and ion mobility for analysis of polypeptide structure on a
      liquid chromatographic time scale.
AB  - Gas-phase hydrogen/deuterium exchange (HDX) is a fast and sensitive, yet
      unharnessed analytical approach for providing information on the structural
      properties of biomolecules, in a complementary manner to mass analysis. Here, we
      describe a simple setup for ND3-mediated millisecond gas-phase HDX inside a mass
      spectrometer immediately after ESI (gas-phase HDX-MS) and show utility for
      studying the primary and higher-order structure of peptides and proteins. HDX was
      achieved by passing N2-gas through a container filled with aqueous deuterated
      ammonia reagent (ND3/D2O) and admitting the saturated gas immediately upstream or
      downstream of the primary skimmer cone. The approach was implemented on three
      commercially available mass spectrometers and required no or minor fully
      reversible reconfiguration of gas-inlets of the ion source. Results from gas
      phase HDX-MS of peptides using the aqueous ND3/D2O as HDX reagent indicate that
      labeling is facilitated exclusively through gaseous ND3, yielding similar results
      to the infusion of purified ND3-gas, while circumventing the complications
      associated with the use of hazardous purified gases. Comparison of the solution
      phase- and gas-phase deuterium uptake of Leu-Enkephalin and Glu-Fibrinopeptide B,
      confirmed that this gas-phase HDX-MS approach allows for labeling of sites
      (heteroatom-bound non-amide hydrogens located on side-chains, N-terminus and C
      terminus) not accessed by classical solution-phase HDX-MS. The simple setup is
      compatible with liquid chromatography and a chip-based automated nanoESI
      interface, allowing for online gas-phase HDX-MS analysis of peptides and proteins
      separated on a liquid chromatographic time scale at increased throughput.
      Furthermore, online gas-phase HDX-MS could be performed in tandem with ion
      mobility separation or electron transfer dissociation, thus enabling multiple
      orthogonal analyses of the structural properties of peptides and proteins in a
      single automated LC-MS workflow. 

PMID- 25375224
TI  - The role of Wnt/beta-catenin signaling in enterocyte turnover during methotrexate
      induced intestinal mucositis in a rat.
AB  - BACKGROUND/AIMS: Intestinal mucositis is a common side-effect in patients who
      receive aggressive chemotherapy. The Wnt signaling pathway is critical for
      establishing and maintaining the proliferative compartment of the intestine. In
      the present study, we tested whether Wnt/beta-catenin signaling is involved in
      methotrexate (MTX)-induced intestinal damage in a rat model. METHODS: Non
      pretreated and pretreated with MTX Caco-2 cells were evaluated for cell
      proliferation and apoptosis using FACS analysis. Adult rats were divided into
      three experimental groups: Control rats; MTX-2 animals were treated with a single
      dose of MTX given IP and were sacrificed on day 2, and MTX-4 rats were treated
      with MTX similar to group B and were sacrificed on day 4. Intestinal mucosal
      damage, mucosal structural changes, enterocyte proliferation, and enterocyte
      apoptosis were measured at sacrifice. Real Time PCR and Western blot was used to
      determine the level of Wnt/beta-catenin related genes and protein expression.
      RESULTS: In the vitro experiment, treatment with MTX resulted in marked decrease
      in early cell proliferation rates following by a 17-fold increase in late cell
      proliferation rates compared to early proliferation. Treatment with MTX resulted
      in a significant increase in early and late apoptosis compared to Caco-2
      untreated cells. In the vivo experiment, MTX-2 and MTX-4 rats demonstrated
      intestinal mucosal hypoplasia. MTX-2 rats demonstrated a significant decrease in
      FRZ-2, Wnt 3A Wnt 5A, beta-catenin, c-myc mRNA expression and a significant
      decrease in beta-catenin and Akt protein levels compared to control animals. Four
      days following MTX administration, rats demonstrated a trend toward a restoration
      of Wnt/beta-catenin signaling especially in ileum. CONCLUSIONS: Wnt/beta-catenin
      signaling is involved in enterocyte turnover during MTX-induced intestinal
      mucositis in a rat.

PMID- 25375225
TI  - Continuous summer export of nitrogen-rich organic matter from the Greenland Ice
      Sheet inferred by ultrahigh resolution mass spectrometry.
AB  - Runoff from glaciers and ice sheets has been acknowledged as a potential source
      of bioavailable dissolved organic matter (DOM) to downstream ecosystems. This
      source may become increasingly significant as glacial melt rates increase in
      response to future climate change. Recent work has identified significant
      concentrations of bioavailable carbon and iron in Greenland Ice Sheet (GrIS)
      runoff. The flux characteristics and export of N-rich DOM are poorly understood.
      Here, we employed electrospray ionization (ESI) coupled to Fourier transform ion
      cyclotron resonance mass spectrometry (FT-ICR MS) to determine the elemental
      compositions of DOM molecules in supraglacial water and subglacial runoff from a
      large GrIS outlet glacier. We provide the first detailed temporal analysis of the
      molecular composition of DOM exported over a full melt season. We find that DOM
      pools in supraglacial and subglacial runoff are compositionally diverse and that
      N-rich material is continuously exported throughout the melt season, as the
      snowline retreats further inland. Identification of protein-like compounds and a
      high proportion of N-rich DOM, accounting for 27-41% of the DOM molecules
      identified by ESI FT-ICR MS, may suggest a microbial provenance and high
      bioavailability of glacially exported DOM to downstream microbial communities. 

PMID- 25375227
TI  - Global validation of a process-based model on vegetation gross primary production
      using eddy covariance observations.
AB  - Gross Primary Production (GPP) is the largest flux in the global carbon cycle.
      However, large uncertainties in current global estimations persist. In this
      study, we examined the performance of a process-based model (Integrated BIosphere
      Simulator, IBIS) at 62 eddy covariance sites around the world. Our results
      indicated that the IBIS model explained 60% of the observed variation in daily
      GPP at all validation sites. Comparison with a satellite-based vegetation model
      (Eddy Covariance-Light Use Efficiency, EC-LUE) revealed that the IBIS simulations
      yielded comparable GPP results as the EC-LUE model. Global mean GPP estimated by
      the IBIS model was 107.50+/-1.37 Pg C year(-1) (mean value +/- standard
      deviation) across the vegetated area for the period 2000-2006, consistent with
      the results of the EC-LUE model (109.39+/-1.48 Pg C year(-1)). To evaluate the
      uncertainty introduced by the parameter Vcmax, which represents the maximum
      photosynthetic capacity, we inversed Vcmax using Markov Chain-Monte Carlo (MCMC)
      procedures. Using the inversed Vcmax values, the simulated global GPP increased
      by 16.5 Pg C year(-1), indicating that IBIS model is sensitive to Vcmax, and
      large uncertainty exists in model parameterization.

PMID- 25375226
TI  - Silencing by H-NS potentiated the evolution of Salmonella.
AB  - The bacterial H-NS protein silences expression from sequences with higher AT
      content than the host genome and is believed to buffer the fitness consequences
      associated with foreign gene acquisition. Loss of H-NS results in severe growth
      defects in Salmonella, but the underlying reasons were unclear. An experimental
      evolution approach was employed to determine which secondary mutations could
      compensate for the loss of H-NS in Salmonella. Six independently derived S.
      Typhimurium hns mutant strains were serially passaged for 300 generations prior
      to whole genome sequencing. Growth rates of all lineages dramatically improved
      during the course of the experiment. Each of the hns mutant lineages acquired
      missense mutations in the gene encoding the H-NS paralog StpA encoding a poorly
      understood H-NS paralog, while 5 of the mutant lineages acquired deletions in the
      genes encoding the Salmonella Pathogenicity Island-1 (SPI-1) Type 3 secretion
      system critical to invoke inflammation. We further demonstrate that SPI-1
      misregulation is a primary contributor to the decreased fitness in Salmonella hns
      mutants. Three of the lineages acquired additional loss of function mutations in
      the PhoPQ virulence regulatory system. Similarly passaged wild type Salmonella
      lineages did not acquire these mutations. The stpA missense mutations arose in
      the oligomerization domain and generated proteins that could compensate for the
      loss of H-NS to varying degrees. StpA variants most able to functionally
      substitute for H-NS displayed altered DNA binding and oligomerization properties
      that resembled those of H-NS. These findings indicate that H-NS was central to
      the evolution of the Salmonellae by buffering the negative fitness consequences
      caused by the secretion system that is the defining characteristic of the
      species. 

PMID- 25375228
TI  - Weight loss in nonalcoholic Fatty liver disease patients in an ambulatory care
      setting is largely unsuccessful but correlates with frequency of clinic visits.
AB  - BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NALFD) is a leading cause
      of liver disease. Weight loss improves clinical features of NAFLD; however,
      maintenance of weight loss outside of investigational protocols is poor. The
      goals of this study were to characterize patterns and clinical predictors of long
      term weight loss in ambulatory patients with NAFLD. METHODS: We retrospectively
      reviewed 924 non-cirrhotic patients with NAFLD presenting to a liver clinic from
      May 1st 2007 to April 30th 2013. Overweight and obese patients were counseled on
      lifestyle modifications for weight loss as per USPSTF guidelines. The primary
      outcome was percent weight change between the first and last recorded visits: %
      weight change  =  (weightinitial - weightfinal)/(weightinitial). Baseline BMI and
      percent BMI change were secondary measures. Predictors of weight loss were
      determined using logistic regression. RESULTS: The mean baseline BMI was 33.3+/
      6.6 kg/m2, and the mean follow-up duration was 17.3+/-17.6 months. Most patients
      with NAFLD were in either overweight (26.1%) or class I obesity (30.5%)
      categories at baseline, while the prevalence of underweight and class III obesity
      was lower (0.2% and 15.4%, respectively). Overall, there was no change in mean
      weight or BMI during the follow-up period, and only 183 patients (19.8%) lost at
      least 5% body weight during the follow up period. Independent predictors of
      weight loss included number of clinic visits and baseline BMI, and patients with
      higher baseline BMI required more clinic visits to lose weight. CONCLUSIONS:
      Weight loss is largely unsuccessful in NAFLD patients in the ambulatory care
      setting. Frequent clinical encounters are associated with weight reduction,
      especially among individuals with high baseline BMI. Future studies are required
      to define effective weight loss strategies in NAFLD patients.

PMID- 25375229
TI  - Positron emission tomography neuroimaging in amyotrophic lateral sclerosis: what
      is new?
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving
      upper and lower motor neurons, extra-motor neurons, microglia and astrocytes. The
      neurodegenerative process results in progressive muscle paralysis and even in
      cognitive impairment. Within the complex diagnostic work-up, positron emission
      tomography (PET) represents a valuable imaging tool in the assessment of patients
      with ALS. PET, by means of different radiotracers (i.e. 18F-fluorodeoxyglucose, 6
      [18F]fluoro-L-dopa, [11C]flumazenil) can assess the status of the wide range of
      brain regions and neural circuits, which can be affected by ALS. Furthermore,
      experimental radiocompounds have been developed for the evaluation of white
      matter, which plays a role in the progression of the disease. Here we present a
      comprehensive review including in different sections the most relevant PET
      studies: studies investigating ALS and ALS-mimicking conditions (especially
      primary lateral sclerosis and other neurodegenerative diseases), articles
      selecting specific subsets of patients (with bulbar or spinal onset), studies
      investigating patients with familial type of ALS, studies evaluating the role of
      the white matter in ALS and papers evaluating the diagnostic sensitivity of PET
      in ALS patients. 

PMID- 25375232
TI  - Dengue disease surveillance: improving data for dengue control.

PMID- 25375230
TI  - Trends in mechanical ventilation among patients hospitalized with acute
      exacerbations of COPD in the United States, 2001 to 2011.
AB  - BACKGROUND: The use of noninvasive ventilation (NIV) in acute exacerbation of
      COPD has increased over time. However, little is known about patient factors
      influencing its use in routine clinical practice. METHODS: This was a
      retrospective cohort study of 723,560 hospitalizations for exacerbation of COPD
      at 475 hospitals between 2001 and 2011. The primary study outcome was the initial
      form of ventilation (NIV or invasive mechanical ventilation [IMV]). Hierarchical
      generalized linear models were used to examine the trends in ventilation and
      patient characteristics associated with receipt of NIV. RESULTS: After adjusting
      for patient and hospital characteristics, initial NIV increased by 15.1% yearly
      (from 5.9% to 14.8%), and initial IMV declined by 3.2% yearly (from 8.7% to
      5.9%); annual exposure to any form of mechanical ventilation increased by 4.4%
      (from 14.1% to 20.3%). Among case subjects treated with ventilation, those aged
      >= 85 years had a 22% higher odds of receiving NIV compared with those aged < 65
      years, while blacks (OR, 0.86) and Hispanics (OR, 0.91) were less likely to be
      treated with NIV than were whites. Cases with a high burden of comorbidities and
      those with concomitant pneumonia had high rates of NIV failure and were more
      likely to receive initial IMV. Use of NIV increased at a faster rate among the
      admissions of the oldest patients relative to the youngest. CONCLUSIONS: The use
      of NIV for COPD exacerbations has increased steadily, whereas IMV use has
      declined. Several patient factors, including age, race, and comorbidities,
      influenced the receipt of NIV. Further research is needed to identify the factors
      driving these patterns.

PMID- 25375233
TI  - Quercetin 7-O-glucoside suppresses nitrite-induced formation of
      dinitrosocatechins and their quinones in catechin/nitrite systems under stomach
      simulating conditions.
AB  - Foods of plant origin contain flavonoids. In the adzuki bean, (+)-catechin,
      quercetin 3-O-rutinoside (rutin), and quercetin 7-O-beta-D-glucopyranoside (Q7G)
      are the major flavonoids. During mastication of foods prepared from the adzuki
      bean, the flavonoids are mixed with saliva and swallowed into the stomach. Here
      we investigated the interactions between Q7G and (+)-catechin at pH 2, which may
      proceed in the stomach after the ingestion of foods prepared from the adzuki
      bean. Q7G reacted with nitrous acid producing nitric oxide (NO) and a glucoside
      of 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone. (+)-Catechin
      reacted with nitrous acid producing NO and 6,8-dinitrosocatechin. The production
      of the dinitrosocatechin was partly suppressed by Q7G, and the suppression
      resulted in the enhancement of Q7G oxidation. 6,8-Dinitrosocatechin reacted
      further with nitrous acid generating the o-quinone, and the quinone formation was
      effectively suppressed by Q7G. In the flavonoids investigated, the suppressive
      effect decreased in the order Q7G~quercetin>kaempferol>quercetin 4'-O
      glucoside>rutin. Essentially the same results were obtained when (-)-epicatechin
      was used instead of (+)-catechin. The results indicate that nitrous acid-induced
      formation of 6,8-dinitrosocatechins and the o-quinones can be suppressed by
      flavonols in the stomach, and that both a hydroxyl group at C3 and ortho-hydroxyl
      groups in the B-ring are required for efficient suppression.

PMID- 25375234
TI  - Maternal factors influencing the decision to breastfeed newborns conceived with
      IVF.
AB  - OBJECTIVES: The breastfeeding initiation rate is extremely disparate worldwide
      and remains low in France, with a breastfeeding initiation rate of 60.2%. Some
      studies have reported increased early parenting difficulties in women who
      conceived with in vitro fertilization (IVF). Our study had two main objectives:
      (1) to determine by a retrospective chart review the demographic and medical
      factors associated with breastfeeding versus formula feeding in women who had
      undergone IVF and (2) to assess by survey study the reasons for the infant
      feeding decision (breastfeeding versus formula feeding) for women who conceived
      by IVF. SUBJECTS AND METHODS: By telephone interviews, we conducted a
      longitudinal nonexperimental cohort study of French women who had a live birth
      after IVF. Fertility data and obstetric outcomes were collected from individual
      medical records. RESULTS: Among women who had a live birth after IVF (n=73), 63%
      (n=46) initiated breastfeeding for a mean duration of 6.2+/-6.2 months. In our
      IVF population, the breastfeeding initiation rate was similar to that in the
      general French population. The following three factors were found to have a
      significant negative influence on breastfeeding initiation: duration of
      infertility greater than 2 years, cesarean delivery, and history of formula
      feeding when the women themselves were newborns. CONCLUSIONS: Long duration of
      infertility and history of cesarean delivery after IVF negatively influenced the
      breastfeeding initiation rate. For this subgroup of patients, postpartum care
      should be enhanced to support the early mother-baby relationship and promote
      breastfeeding.

PMID- 25375235
TI  - NMR-based detection of hydrogen/deuterium exchange in liposome-embedded membrane
      proteins.
AB  - Membrane proteins play key roles in biology. Determination of their structure in
      a membrane environment, however, is highly challenging. To address this
      challenge, we developed an approach that couples hydrogen/deuterium exchange of
      membrane proteins to rapid unfolding and detection by solution-state NMR
      spectroscopy. We show that the method allows analysis of the solvent protection
      of single residues in liposome-embedded proteins such as the 349-residue Tom40,
      the major protein translocation pore in the outer mitochondrial membrane, which
      has resisted structural analysis for many years. 

PMID- 25375236
TI  - New Strategies for the Treatment of Phenylketonuria (PKU).
AB  - Phenylketonuria (PKU) was the first inherited metabolic disease in which dietary
      treatment was found to prevent the disease's clinical features. Treatment of
      phenylketonuria remains difficult due to progressive decrease in adherence to
      diet and the presence of neurocognitive defects despite therapy. This review aims
      to summarize the current literature on new treatment strategies. Additions to
      treatment include new, more palatable foods based on glycomacropeptide that
      contains very limited amount of aromatic amino acids, the administration of large
      neutral amino acids to prevent phenylalanine entry into the brain or
      tetrahydropterina cofactor capable of increasing residual activity of
      phenylalanine hydroxylase. Moreover, human trials have recently been performed
      with subcutaneous administration of phenylalanine ammonia-lyase, and further
      efforts are underway to develop an oral therapy containing phenylanine ammonia
      lyase. Gene therapy also seems to be a promising approach in the near future. 

PMID- 25375238
TI  - Self-esteem as a mediator between personality traits and body esteem: path
      analyses across gender and race/ethnicity.
AB  - Prior literature examines the direct relationship between personality traits and
      body esteem. This article explores the possibility that self-esteem mediates this
      relationship. 165 undergraduate women and 133 men (age 18-21; 42.6% Hispanic,
      28.9% Asian, 28.5% Caucasian) completed items measuring personality traits (Big
      Five), self-esteem, and body esteem. Path analyses were used to test for
      mediation. The analyses confirmed that in both men and women self-esteem mediated
      the relationship between three personality traits and body esteem: higher levels
      of conscientiousness, emotional stability, and extraversion were associated with
      higher self-esteem and consequently higher body esteem. Once self-esteem was
      included in the model the relationships between personality traits and body
      esteem were not significant, suggesting full mediation. In addition, the analyses
      revealed several racial/ethnic differences. In Asian American participants, self
      esteem mediated the relationship between conscientiousness and body esteem and
      between emotional stability and body esteem. In Hispanic Americans, self-esteem
      mediated the relationship between conscientiousness and body esteem and between
      extraversion and body esteem. And in Caucasian Americans, self-esteem mediated
      the relationship between emotional stability and body esteem and between
      extraversion and body esteem. The most important contribution of this study is
      evidence for an indirect relationship between personality traits and body esteem,
      with this relationship being mediated by self-esteem. This has important
      implications for the study of personality and eating disorders in young adults,
      most particularly implying a need for more emphasis on self-esteem as a predictor
      of body image problems. 

PMID- 25375237
TI  - Insight into a molecular interaction force supporting peptide backbones and its
      implication to protein loops and folding.
AB  - Although not being classified as the most fundamental protein structural elements
      like alpha-helices and beta-strands, the loop segment may play considerable roles
      for protein stability, flexibility, and dynamic activity. Meanwhile, the protein
      loop is also quite elusive; i.e. its interactions with the other parts of protein
      as well as its own shape-maintaining forces have still remained as a puzzle or at
      least not quite clear yet. Here, we report a molecular force, the so-called polar
      hydrogen-pi interaction (Hp-pi), which may play an important role in supporting
      the backbones of protein loops. By conducting the potential energy surface
      scanning calculations on the quasi pi-plane of peptide bond unit, we have
      observed the following intriguing phenomena: (1) when the polar hydrogen atom of
      a peptide unit is perpendicularly pointing to the pi-plane of other peptide bond
      units, a remarkable Hp-pi interaction occurs; (2) the interaction is distance and
      orientation dependent, acting in a broad space, and belonging to the 'point-to
      plane' one. The molecular force reported here may provide useful interaction
      concepts and insights into better understanding the loop's unique stability and
      flexibility feature, as well as the driving force of the protein global folding. 

PMID- 25375239
TI  - Polymer-confined colloidal monolayer: a reusable soft photomask for rapid wafer
      scale nanopatterning.
AB  - We demonstrate the repeated utilization of self-assembled colloidal spheres for
      rapid nanopattern generations. Highly ordered micro-/nanosphere arrays were
      interlinked and confined by a soft transparent polymer (polydimethylsiloxane,
      PDMS), which can be used as light-focusing elements/photomasks for area-selective
      exposures of photoresist in contact. Because of the stiffness of the colloidal
      spheres, the photomasks do not encounter feature-deformation problems, enabling
      reliable production of highly uniform patterns over large areas. The geometrical
      feature of the patterns, including the size, pitch, and even the shape, can be
      finely tuned by adjusting the mask design and exposure time. The obtained
      patterns could be used as deposition or etching mask, allowing easy pattern
      transfer for various applications. 

PMID- 25375242
TI  - Molecular docking via olefinic OH...pi interactions: a bulky alkene model system
      and its cooperativity.
AB  - Complexes of t-butyl alcohol with norbornene and its monocyclic constituents
      cyclopentene and cyclohexene are studied via their OH stretching fundamental
      transitions in supersonic jet expansions. Compared to OH...OH hydrogen bonds, the
      spectral shifts due to OH...pi bonding in the mixed dimers are reduced by a
      factor of 2. Mixed trimers show substantially different spectral signatures due
      to cooperative effects. Regioselective docking on the two sides of the double
      bond in norbornene is observed. Harmonic modeling of the spectra using dispersion
      corrected hybrid functionals is quite successful, suggesting a high predictive
      power for this poorly explored class of complexes between alcohols and alkenes. 

PMID- 25375243
TI  - Primates living outside protected habitats are more stressed: the case of black
      howler monkeys in the Yucatan Peninsula.
AB  - The non-invasive monitoring of glucocorticoid hormones allows for the assessment
      of the physiological effects of anthropogenic disturbances on wildlife. Variation
      in glucocorticoid levels of the same species between protected and unprotect
      areas seldom has been measured, and the available evidence suggests that this
      relationship may depend on species-specific habitat requirements and biology. In
      the present study we focused on black howler monkeys (Alouatta pigra), a canopy
      dwelling primate species, as a case study to evaluate the physiological
      consequences of living in unprotected areas, and relate them with intragroup
      competition and competition with extragroup individuals. From February 2006 to
      September 2007 we collected 371 fecal samples from 21 adults belonging to five
      groups (two from protected and three from unprotected areas) in Campeche, Mexico.
      We recorded agonistic interactions within groups and encounters with other groups
      (1,200 h of behavioral observations), and determined fecal glucocorticoid
      metabolite (FGM) concentrations with radioimmunoassays. We used linear mixed
      models and Akaike's information criterion to choose the best model explaining
      variation in FGM concentrations between protected and unprotected areas
      calculated from five categorical variables: habitat type (protected vs.
      unprotected), participation in agonistic interactions, intergroup encounters, sex
      and female reproductive state, and season. The best model included habitat type,
      the interaction between habitat type and agonism, and the interaction between
      habitat type and season. FGM concentrations were higher in unprotected habitats,
      particularly when individuals were involved in agonistic interactions; seasonal
      variation in FGM concentrations was only detected in protected habitats. High FGM
      concentrations in black howler monkeys living in unprotected habitats are
      associated with increased within-group food competition and probably associated
      with exposure to anthropogenic stressors and overall food scarcity. Because
      persistent high GC levels can be detrimental to health and fitness, populations
      living in disturbed unprotected areas may not be viable in the long-term. 

PMID- 25375241
TI  - A functional approach reveals a genetic and physical interaction between
      ribonucleotide reductase and CHK1 in mammalian cells.
AB  - Ribonucleotide reductase (RNR) enzyme is composed of the homodimeric RRM1 and
      RRM2 subunits, which together form a heterotetramic active enzyme that catalyzes
      the de novo reduction of ribonucleotides to generate deoxyribonucleotides
      (dNTPs), which are required for DNA replication and DNA repair processes. In this
      study, we show that ablation of RRM1 and RRM2 by siRNA induces G1/S phase arrest,
      phosphorylation of Chk1 on Ser345 and phosphorylation of gamma-H2AX on S139.
      Combinatorial ablation of RRM1 or RRM2 and Chk1 causes a dramatic accumulation of
      gamma-H2AX, a marker of double-strand DNA breaks, suggesting that activation of
      Chk1 in this context is essential for suppression of DNA damage. Significantly,
      we demonstrate for the first time that Chk1 and RNR subunits co-immunoprecipitate
      from native cell extracts. These functional genomic studies suggest that RNR is a
      critical mediator of replication checkpoint activation. 

PMID- 25375240
TI  - The kinetochore protein Kis1/Eic1/Mis19 ensures the integrity of mitotic spindles
      through maintenance of kinetochore factors Mis6/CENP-I and CENP-A.
AB  - Microtubules play multiple roles in a wide range of cellular phenomena, including
      cell polarity establishment and chromosome segregation. A number of microtubule
      regulators have been identified, including microtubule-associated proteins and
      kinases, and knowledge of these factors has contributed to our molecular
      understanding of microtubule regulation of each relevant cellular process. The
      known regulators, however, are insufficient to explain how those processes are
      linked to one another, underscoring the need to identify additional regulators.
      To find such novel mechanisms and microtubule regulators, we performed a screen
      that combined genetics and microscopy for fission yeast mutants defective in
      microtubule organization. We isolated approximately 900 mutants showing defects
      in either microtubule organization or the nuclear envelope, and these mutants
      were classified into 12 categories. We particularly focused on one mutant, kis1,
      which displayed spindle defects in early mitosis. The kis1 mutant frequently
      failed to assemble a normal bipolar spindle. The responsible gene encoded a
      kinetochore protein, Mis19 (also known as Eic1), which localized to the interface
      of kinetochores and spindle poles. We also found that the inner kinetochore
      proteins Mis6/CENP-I and Cnp1/CENP-A were delocalized from kinetochores in the
      kis1 cells and that kinetochore-microtubule attachment was defective. Another
      mutant, mis6, also displayed similar spindle defects. We conclude that Kis1 is
      required for inner kinetochore organization, through which Kis1 ensures
      kinetochore-microtubule attachment and spindle integrity. Thus, we propose an
      unexpected relationship between inner kinetochore organization and spindle
      integrity. 

PMID- 25375245
TI  - An unusual cause of sudden hearing loss. Probable neurosarcoidosis (NS).

PMID- 25375244
TI  - Risk factors and outcomes of Stenotrophomonas maltophilia bacteraemia: a
      comparison with bacteraemia caused by Pseudomonas aeruginosa and Acinetobacter
      species.
AB  - Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen that
      exhibits intrinsic resistance to various antimicrobial agents. However, the risk
      factors for SM bacteraemia have not been sufficiently evaluated. From January
      2005 to September 2012, we retrospectively compared the clinical backgrounds and
      outcomes of SM bacteraemic patients (SM group) with those of bacteraemic patients
      due to Pseudomonas aeruginosa (PA group) or Acinetobacter species (AC group). DNA
      genotyping of the SM isolates using the Diversilab system was performed to
      investigate the genetic relationships among the isolates. The SM, PA, and AC
      groups included 54, 167, and 69 patients, respectively. Nine of 17 patients in
      the SM group receiving trimethoprim-sulfamethoxazole prophylaxis developed SM
      bacteraemia. Independent risk factors for SM bacteraemia were the use of
      carbapenems and antipseudomonal cephalosporins and SM isolation within 30 days
      prior to the onset of bacteraemia. Earlier SM isolation was observed in 32 of 48
      patients (66.7%) with SM bacteraemia who underwent clinical microbiological
      examinations. Of these 32 patients, 15 patients (46.9%) had the same focus of
      bacteraemia as was found in the previous isolation site. The 30-day all-cause
      mortality rate among the SM group (33.3%) was higher than that of the PA group
      (21.5%, p = 0.080) and the AC group (17.3%, p = 0.041). The independent factor
      that was associated with 30-day mortality was the SOFA score. DNA genotyping of
      SM isolates and epidemiological data suggested that no outbreak had occurred. SM
      bacteraemia was associated with high mortality and should be considered in
      patients with recent use of broad-spectrum antibiotics or in patients with recent
      isolation of the organism.

PMID- 25375247
TI  - Nanoconfinement of pyrene in mesostructured silica nanoparticles for trace
      detection of TNT in the aqueous phase.
AB  - This article describes the preparation of pyrene confined mesostructured silica
      nanoparticles for the trace detection of trinitrotoluene (TNT) in the aqueous
      phase. Pyrene confined mesostructured silica nanoparticles were prepared using a
      facile one-pot method where pyrene molecules were first encapsulated in the
      hydrophobic parts of cetyltrimethylammonium micelles and then silica polymerized
      around these micelles. The resulting hybrid particles have sizes of around 75 nm
      with fairly good size distribution. Also, they are highly dispersible and
      colloidally stable in water. More importantly, they exhibit bright and highly
      stable pyrene excimer emission. We demonstrated that excimer emission of the
      particles exhibits a rapid, sensitive and visual quenching response against TNT.
      The detection limit for TNT was determined to be 12 nM. Furthermore, excimer
      emission of pyrene shows significantly high selectivity for TNT. 

PMID- 25375248
TI  - Confirmatory factor analysis of the Sport Emotion Questionnaire in organisational
      environments.
AB  - The Sport Emotion Questionnaire (SEQ) (Jones, M. V., Lane, A. M., Bray, S. R.,
      Uphill, M., & Catlin, J. (2005). Development and validation of the SEQ. Journal
      of Sport and Exercise Psychology, 27, 407-431) was developed and initially
      validated to assess sport performers' pre-competitive emotions. The purpose of
      this study was to test the factor structure of the SEQ in a different environment
      (viz. organisational) and at a different time point (viz. the past month). A
      further aim was to examine if the SEQ was invariant across different groups of
      sport performers. A diverse sample of athletes (n = 1277) completed the
      questionnaire. Fit indices from confirmatory factor analyses provided partial
      support for the hypothesised measurement model, with equal or better fit
      demonstrated than evident in initial validation. The comparative fit index values
      were above acceptable guidelines for all factors at subscale level. Evidence was
      also found for the invariance of the SEQ across different groups. Overall, the
      findings support the reliability and validity of the SEQ as a measure of the
      emotions experienced by sport performers in an organisational environment during
      the past month.

PMID- 25375246
TI  - Neural stem cell-mediated intratumoral delivery of gold nanorods improves
      photothermal therapy.
AB  - Plasmonic photothermal therapy utilizes biologically inert gold nanorods (AuNRs)
      as tumor-localized antennas that convert light into heat capable of eliminating
      cancerous tissue. This approach has lower morbidity than surgical resection and
      can potentially synergize with other treatment modalities including chemotherapy
      and immunotherapy. Despite these advantages, it is still challenging to obtain
      heating of the entire tumor mass while avoiding unnecessary collateral damage to
      surrounding healthy tissue. It is therefore critical to identify innovative
      methods to distribute an effective concentration of AuNRs throughout tumors
      without depositing them in surrounding healthy tissue. Here we demonstrate that
      AuNR-loaded, tumor-tropic neural stem cells (NSCs) can be used to improve the
      intratumoral distribution of AuNRs. A simple UV-vis technique for measuring AuNR
      loading within NSCs was established. It was then confirmed that NSC viability is
      unimpaired following AuNR loading and that NSCs retain AuNRs long enough to
      migrate throughout tumors. We then demonstrate that intratumoral injections of
      AuNR-loaded NSCs are more efficacious than free AuNR injections, as evidenced by
      reduced recurrence rates of triple-negative breast cancer (MDA-MB-231) xenografts
      following NIR exposure. Finally, we demonstrate that the distribution of AuNRs
      throughout the tumors is improved when transported by NSCs, likely resulting in
      the improved efficacy of AuNR-loaded NSCs as compared to free AuNRs. These
      findings highlight the advantage of combining cellular therapies and
      nanotechnology to generate more effective cancer treatments. 

PMID- 25375249
TI  - Rapid and simultaneous quantification of levetiracetam and its carboxylic
      metabolite in human plasma by liquid chromatography tandem mass spectrometry.
AB  - A simple liquid chromatography tandem mass spectrometry method was developed and
      validated according to the guidelines of the US Food and Drug Administration and
      the European Medicines Agency for a simultaneous quantification of levetiracetam
      (LEV) and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma
      sample was prepared by a simple and direct protein precipitation with 0.450 mL
      acetonitrile (ACN) containing 1 ug/mL of internal standard (IS, diphenhydramine),
      then vortex mixed and centrifuged. A 0.100 mL of the clear supernatant was
      diluted with 0.400 mL water and well mixed. A 0.010 mL of the resultant solution
      was injected into an Agilent Zorbax SB-C18 (2.1 mm*100 mm, 3.5 um) column with an
      isocratic elution at 0.5 mL/min using a mixture of 0.1% formic acid in water and
      ACN (40:60 v/v). Detection was performed using an AB Sciex API 3000 triple
      quadrupole mass spectrometer, equipped with a Turbo Ion Spray source, operating
      in a positive mode: LEV at transition 171.1>154.1, UCB L057 at 172.5>126.1, and
      IS at 256.3>167.3; with an assay run time of 2 minutes. The lower limit of
      quantification (LLOQ) for both LEV and UCB L057 was validated at 0.5 ug/mL, while
      their lower limit of detection (LOD) was 0.25 ug/mL. The calibration curves were
      linear between 0.5 and 100 ug/mL for both analytes. The inaccuracy and
      imprecision of both intra-assay and inter-assay were less than 10%. Matrix
      effects were consistent between sources of plasma and the recoveries of all
      compounds were between 100% and 110%. Stability was established under various
      storage and processing conditions. The carryovers from both LEV and UCB L057 were
      less than 6% of the LLOQ and 0.13% of the IS. This assay method has been
      successfully applied to a population pharmacokinetic study of LEV in patients
      with epilepsy.

PMID- 25375250
TI  - Let's face it--complex traits are just not that simple.

PMID- 25375251
TI  - Regulation of mRNA abundance by polypyrimidine tract-binding protein-controlled
      alternate 5' splice site choice.
AB  - Alternative splicing (AS) provides a potent mechanism for increasing protein
      diversity and modulating gene expression levels. How alternate splice sites are
      selected by the splicing machinery and how AS is integrated into gene regulation
      networks remain important questions of eukaryotic biology. Here we report that
      polypyrimidine tract-binding protein 1 (Ptbp1/PTB/hnRNP-I) controls alternate 5'
      and 3' splice site (5'ss and 3'ss) usage in a large set of mammalian transcripts.
      A top scoring event identified by our analysis was the choice between competing
      upstream and downstream 5'ss (u5'ss and d5'ss) in the exon 18 of the Hps1 gene.
      Hps1 is essential for proper biogenesis of lysosome-related organelles and loss
      of its function leads to a disease called type 1 Hermansky-Pudlak Syndrome (HPS).
      We show that Ptbp1 promotes preferential utilization of the u5'ss giving rise to
      stable mRNAs encoding a full-length Hps1 protein, whereas bias towards d5'ss
      triggered by Ptbp1 down-regulation generates transcripts susceptible to nonsense
      mediated decay (NMD). We further demonstrate that Ptbp1 binds to pyrimidine-rich
      sequences between the u5'ss and d5'ss and activates the former site rather than
      repressing the latter. Consistent with this mechanism, u5'ss is intrinsically
      weaker than d5'ss, with a similar tendency observed for other genes with Ptbp1
      induced u5'ss bias. Interestingly, the brain-enriched Ptbp1 paralog
      Ptbp2/nPTB/brPTB stimulated the u5'ss utilization but with a considerably lower
      efficiency than Ptbp1. This may account for the tight correlation between Hps1
      with Ptbp1 expression levels observed across mammalian tissues. More generally,
      these data expand our understanding of AS regulation and uncover a post
      transcriptional strategy ensuring co-expression of a subordinate gene with its
      master regulator through an AS-NMD tracking mechanism.

PMID- 25375252
TI  - Beyond branching: multiknot structured polymer for gene delivery.
AB  - Polymer-based transfection vectors are increasingly becoming the preferred
      alternative to viral vectors thanks to their safety and ease of production, but
      low transfection potency has limited their application. Many polycationic vectors
      show high efficiency in vitro, but their excessive charge density makes them
      toxic for in vivo applications. Herein, we demonstrate the synthesis of new and
      unique disulfide-reducible polymeric gene nanocarriers that exhibit significantly
      enhanced transfection potency and low cytotoxicity, particularly in skin cells,
      surpassing the efficiency of the well-known transfection reagents
      polyethylenimine (PEI) and Lipofectamine2000. The unique three-dimensional (3D)
      "multiknot" vectors were synthesized from in situ deactivation enhanced atom
      transfer radical (co)polymerization (DE-ATRP) of multivinyl monomers (MVMs). The
      high transfection levels and low toxicity of this multiknot structured polymer in
      vitro, combined with its ability to mediate collagen VII expression in 3D skin
      equivalents made from cells of recessive dystrophic epidermolysis bullosa
      patients, demonstrates its use as a platform nanotechnology which should be
      investigated further for dermatological disease therapies. Our findings suggest
      that the marked improvements stem from the dense multiknot architecture and
      degradable property, which facilitate both the binding and releasing process of
      the plasmid DNA.

PMID- 25375254
TI  - Development of cell-penetrating R7 fragment-conjugated helical peptides as
      inhibitors of estrogen receptor-mediated transcription.
AB  - The heptaarginine (R7)-conjugated peptide 5 was designed and synthesized as an
      inhibitor of ER-coactivator interactions and ER-mediated transcription at the
      cellular level. The R7-conjugated peptide 5 was able to enter ER-positive T47D
      cells efficiently, and treatment with 3 MUM of 5 downregulated the mRNA
      expression of pS2 (an ER-mediated gene) by 87%. 

PMID- 25375253
TI  - Functional fission of parvalbumin interneuron classes during fast network events.
AB  - Fast spiking, parvalbumin (PV) expressing hippocampal interneurons are classified
      into basket, axo-axonic (chandelier), and bistratified cells. These cell classes
      play key roles in regulating local circuit operations and rhythmogenesis by
      releasing GABA in precise temporal patterns onto distinct domains of principal
      cells. In this study, we show that each of the three major PV cell classes
      further splits into functionally distinct sub-classes during fast network events
      in vivo. During the slower (<10 Hz) theta oscillations, each cell class exhibited
      its own characteristic, relatively uniform firing behavior. However, during
      faster (>90 Hz) oscillations, within-class differences in PV interneuron
      discharges emerged, which segregated along specific features of dendritic
      structure or somatic location. Functional divergence of PV sub-classes during
      fast but not slow network oscillations effectively doubles the repertoire of
      spatio-temporal patterns of GABA release available for rapid circuit operations. 

PMID- 25375255
TI  - Prospects of mHealth services in Bangladesh: recent evidence from Chakaria.
AB  - INTRODUCTION: Bangladesh has a serious shortage of qualified health workforce.
      The limited numbers of trained service providers are based in urban areas, which
      limits access to quality healthcare for the rural population. mHealth provides a
      new opportunity to ensure access to quality services to the population. A recent
      review suggested that there are 19 mHealth initiatives in the country. This paper
      reports findings on people's knowledge, perception, use, cost and compliance with
      advice received from mHealth services from a study carried out during 2012-13 in
      Chakaria, a rural sub-district in Bangladesh. METHODS: A total of 4,915 randomly
      chosen respondents aged 18 years and above were interviewed. RESULTS: Household
      ownership of mobile phones in the study area has increased from 2% in 2004 to 81%
      in 2012; 45% of the respondents reported that they had mobile phones. Thirty-one
      percent of the respondents were aware of the use of mobile phones for healthcare.
      Very few people were aware of the available mHealth services. Males, younger age
      group, better educated, and those from richer households were more knowledgeable
      about the existing mHealth services. Among the respondents who sought healthcare
      in the preceding two weeks of the survey, only 2% used mobile phones for
      healthcare. Adherence to the advice from the healthcare providers in terms of
      purchasing and taking the drugs was somewhat similar between the patients who
      used mobile phone for consultation versus making a physical visit. CONCLUSIONS:
      The high penetration of mobile phones into the society provides a unique
      opportunity to use the mHealth technology for consulting healthcare providers.
      Although knowledge of the existence of mHealth services was low, it was
      encouraging that the compliance with the prescriptions was almost similar for
      advice received through mobile phone and physical visits. The study revealed
      clear indications that society is looking forward to embracing the mHealth
      technology.

PMID- 25375256
TI  - Psycho-socioeconomic factors affecting complementary and alternative medicine use
      among selected rural communities in Malaysia: a cross-sectional study.
AB  - INTRODUCTION: The use of complementary and alternative medicine (CAM) as a source
      of cure has gained much spectrum worldwide, despite skeptics and advocates of
      evidence-based practice conceptualized such therapies as human nostrum.
      OBJECTIVE: This study aimed to explore the factors affecting CAM use among rural
      communities in Malaysia. METHODS: A cross-sectional study was carried out on 288
      occupants across four rural villages within the District of Selama, Perak,
      Malaysia. A survey that consisted of socio-economic characteristics, history of
      CAM use and the validated Holistic Complementary and Alternative Medicine
      Questionnaire (HCAMQ) were used. RESULTS: The prevalence of self-reported CAM use
      over the past one year was 53.1%. Multiple logistic regression analyses yielded
      three significant predictors of CAM use: monthly household income of less than
      MYR 2500, higher education level, and positive attitude towards CAM. CONCLUSION:
      Psycho-socioeconomic factors were significantly associated with CAM use among
      rural communities in Malaysia.

PMID- 25375258
TI  - Complete stereochemistry and preliminary structure-activity relationship of
      rakicidin A, a hypoxia-selective cytotoxin from Micromonospora sp.
AB  - The complete stereochemistry of rakicidin A, a hypoxia-selective cytotoxin
      produced by Micromonospora sp., was unambiguously established by extensive
      chemical degradation and derivatization studies. During the PGME derivatization
      based configurational analysis of 3-hydroxy-2,4,16-trimethylheptadecanoic acid,
      an irregular Deltadelta distribution was observed, which necessitated further
      acylation of the 3-hydroxy group to resolve the inconsistency. A hydrogenated
      derivative of rakicidin A, its ring-opened product, and two congeners with
      different alkyl chain lengths were tested for hypoxia-selective cytotoxicity. The
      results indicated that both the conjugated diene unit and appropriate chain
      length are essential for the unique activity of rakicidin A. 

PMID- 25375257
TI  - Safety and efficacy of percutaneous mitral valve repair using the MitraClip(r)
      system in patients with diabetes mellitus.
AB  - BACKGROUND: Patients with diabetes mellitus show a negative outcome in
      percutaneous coronary intervention, aortic valve replacement and cardiac surgery.
      The impact of diabetes on patients undergoing treatment of severe mitral
      regurgitation (MR) using the MitraClip system is not known. We therefore sought
      to assess whether percutaneous mitral valve repair with the MitraClip system is
      safe and effective in patients with diabetes mellitus. METHODS AND RESULTS: We
      included 58 patients with severe and moderate-to-severe MR in an open-label
      observational single-center study. Ninteen patients were under oral medication or
      insulin therapy for type II diabetes mellitus. MitraClip devices were
      successfully implanted in all patients with diabetes and in 97.4% (n = 38) of
      patients without diabetes (p = 0.672). Periprocedural major cardiac adverse and
      cerebrovascular events (MACCE) occurred in 5.1% (n = 2) of patients without
      diabetes whereas patients with diabetes did not show any MACCE (p = 0.448). 30
      day mortality was 1.7% (n = 1) with no case of death in the diabetes group. Short
      term follow up of three months showed a significant improvement of NYHA class and
      quality of life evaluated by the Minnesota Living with Heart Failure
      Questionnaire in both groups, with no changes in the 6-minute walk test.
      CONCLUSIONS: Mitral valve repair with the MitraClip system is safe and effective
      in patients with type II diabetes mellitus. TRIAL REGISTRATION: MitraClip
      Registry NCT02033811.

PMID- 25375259
TI  - Nanostructured lipid carriers: effect of solid phase fraction and distribution on
      the release of encapsulated materials.
AB  - Emulsions, solid lipid nanoparticles (SLN), and nanostructured lipid carriers
      (NLC) containing a mix of liquid and solid domains are of interest as
      encapsulation vehicles for hydrophobic compounds. Studies of the release rate
      from these particles yield contradictory results: Some find that increasing the
      fraction of solid phase increases the rate of release and others the opposite. In
      this paper we study the release of encapsulated materials from lipid-based
      nanoparticles using Monte Carlo simulations. We find that, quite surprisingly,
      the release rate is largely insensitive to the size of solid domains or the
      fraction of solid phase. However, the distribution of the domains significantly
      affects the rate of release: Solid domains located at the interface with the
      surrounding solution inhibit transport, while nanoparticles where the solid
      domains are concentrated in the center enhance it. The latter can lead to release
      rates in NLCs that are faster than in the equivalent emulsions. We conclude that
      controlling the release rate from NLCs requires the ability to determine the
      location and distribution of the solid phase, which may be achieved through
      choice of the surfactants stabilizing the particles, incorporation of nucleation
      sites, and/or the cooling rates and temperatures. 

PMID- 25375260
TI  - Gelation: the role of sugars and polyols on gelatin and agarose.
AB  - Gelation is enhanced by the addition of sugars and polyols. How, at a microscopic
      level, do such cosolvents enhance gelation? The following two different
      hypotheses have been proposed so far to answer this question: (i) enhancement of
      water structure around the biopolymer induced by cosolvents; (ii) exclusion of
      cosolvents from biopolymer surfaces. To examine the validity of the above
      hypotheses, as well as to quantify the driving forces of cosolvent-induced
      gelation, we have constructed a statistical thermodynamic theory of gelation, by
      extending our Kirkwood-Buff theory of cosolvency; biopolymer-water and biopolymer
      cosolvent interactions can both be determined from thermodynamic data. The
      exclusion of cosolvents is shown to be the dominant contribution, whereas the
      hydration change is a minor contribution, which may be important only so far as
      to mediate the exclusion of cosolvents. 

PMID- 25375261
TI  - Prediction of potential wrong-way entries at exit ramps of signalized partial
      cloverleaf interchanges.
AB  - BACKGROUND: Several previous studies, based upon wrong-way driving (WWD) crash
      history, have demonstrated that partial cloverleaf (parclo) interchanges are more
      susceptible to WWD movements than others. Currently, there is not a method
      available to predict WWD incidents and to prioritize parclo interchanges for
      implementing safety countermeasures for reducing WWD crashes. OBJECTIVES: The
      focus of this manuscript is to develop a mathematical method to estimate the
      probability of WWD incidents at exit ramp terminals of this type of interchange.
      METHODS: VISSIM traffic simulation models, calibrated by field data, are utilized
      to estimate the number of potential WWD maneuvers under various traffic volumes
      on exit ramps and crossroads. The Poisson distribution model was implemented
      without field observation and crash data. RESULTS: A comparison between the field
      data and simulation outputs revealed that the developed model enjoys an
      acceptable level of accuracy. The proposed model is largely sensitive to left
      turn volume toward an entrance ramp (LVE) than stopped vehicles at an exit ramp
      (SVE). The results indicated that potential WWD events increase when LVEs
      increase and SVEs decrease. Also, the probability of WWD event decreases as road
      users are more familiar with the facility. CONCLUSION: The proposed method can
      diminish one of the challenges in front of transportation engineers, which is to
      identify high WWD crash locations due to insufficient information in crash
      reports. The results are helpful for transportation professionals to take
      proactive steps to identify locations for implementing safety countermeasures at
      high risk signalized parclo interchanges.

PMID- 25375263
TI  - Ovarian acyclicity in zoo African elephants (Loxodonta africana) is associated
      with high body condition scores and elevated serum insulin and leptin.
AB  - The purpose of the present study was to determine whether excessive body fat and
      altered metabolic hormone concentrations in the circulation were associated with
      ovarian acyclicity in the world's largest land mammal, the African elephant. We
      compared body condition, glucose, insulin and leptin concentrations and the
      glucose-to-insulin ratio (G:I) between cycling (n=23; normal 14-16 week cycles
      based on serum progestagens for at least 2 years) and non-cycling (n=23;
      consistent baseline progestagen concentrations for at least 2 years) females. A
      validated body condition score (BCS) index (five-point scale; 1=thinnest,
      5=fattest) was used to assess the degree of fatness of the study elephants. The
      mean BCS of non-cycling elephants was higher than that of their cycling
      counterparts. There were differences in concentrations of serum metabolic
      biomarkers, with non-cycling elephants in the BCS 5 category having higher leptin
      and insulin concentrations and a lower G:I ratio than cycling BCS 5 females.
      Using 'non-cycling' as the outcome variable in regression models, high BCS was a
      strong predictor of a non-cycling status. This study provides the first evidence
      that ovarian acyclicity in zoo African elephants is associated with body
      condition indicative of obesity, as well as elevated, perturbed biomarkers of
      metabolic status. 

PMID- 25375262
TI  - A comparative study and a phylogenetic exploration of the compositional
      architectures of mammalian nuclear genomes.
AB  - For the past four decades the compositional organization of the mammalian genome
      posed a formidable challenge to molecular evolutionists attempting to explain it
      from an evolutionary perspective. Unfortunately, most of the explanations adhered
      to the "isochore theory," which has long been rebutted. Recently, an alternative
      compositional domain model was proposed depicting the human and cow genomes as
      composed mostly of short compositionally homogeneous and nonhomogeneous domains
      and a few long ones. We test the validity of this model through a rigorous
      sequence-based analysis of eleven completely sequenced mammalian and avian
      genomes. Seven attributes of compositional domains are used in the analyses: (1)
      the number of compositional domains, (2) compositional domain-length
      distribution, (3) density of compositional domains, (4) genome coverage by the
      different domain types, (5) degree of fit to a power-law distribution, (6)
      compositional domain GC content, and (7) the joint distribution of GC content and
      length of the different domain types. We discuss the evolution of these
      attributes in light of two competing phylogenetic hypotheses that differ from
      each other in the validity of clade Euarchontoglires. If valid, the murid genome
      compositional organization would be a derived state and exhibit a high similarity
      to that of other mammals. If invalid, the murid genome compositional organization
      would be closer to an ancestral state. We demonstrate that the compositional
      organization of the murid genome differs from those of primates and
      laurasiatherians, a phenomenon previously termed the "murid shift," and in many
      ways resembles the genome of opossum. We find no support to the "isochore
      theory." Instead, our findings depict the mammalian genome as a tapestry of
      mostly short homogeneous and nonhomogeneous domains and few long ones thus
      providing strong evidence in favor of the compositional domain model and seem to
      invalidate clade Euarchontoglires. 

PMID- 25375264
TI  - Human taste and umami receptor responses to chemosensorica generated by Maillard
      type N2-alkyl- and N2-arylthiomethylation of guanosine 5'-monophosphates.
AB  - Structural modification of the exocyclic amino function of guanosine 5'
      monophosphate (5'-GMP) by Maillard-type reactions with reducing carbohydrates was
      recently found to increase the umami-enhancing activity of the nucleotide upon S
      N(2)-1-carboxyalkylation and S-N(2)-(1-alkylamino)carbonylalkylation,
      respectively. Since the presence of sulfur atoms in synthetic N(2)-alkylated
      nucleotides was reported to be beneficial for sensory activity, a versatile
      Maillard-type modification of 5'-GMP upon reaction with glycine's Strecker
      aldehyde formaldehyde and organic thiols was performed in the present study. A
      series of N(2)-(alkylthiomethyl)guanosine and N(2)-(arylthiomethyl)guanosine 5'
      monophosphates was generated and the compounds were evaluated to what extent they
      enhance the umami response to monosodium L-glutamate in vivo by a paired-choice
      comparison test using trained human volunteers and in vitro by means of cell
      based umami taste receptor assay. Associated with a high umami-enhancing activity
      (beta-value 5.1), N(2)-(propylthiomethyl)guanosine 5'-monophosphate could be
      generated when 5'-GMP reacted with glucose, glycine, and the onion-derived
      odorant 1-propanethiol, thus opening a valuable avenue to produce high-potency
      umami-enhancing chemosensorica from food-derived natural products by kitchen-type
      chemistry.

PMID- 25375265
TI  - A full picture of enzymatic catalysis by hydroxynitrile lyases from Hevea
      brasiliensis: protonation dependent reaction steps and residue-gated movement of
      the substrate and the product.
AB  - Hydroxynitrile lyases (HNLs) defend plants from herbivores and microbial attack
      by releasing cyanide from hydroxynitriles. The reverse process has been
      productively applied to bioorganic syntheses of pharmaceuticals and
      agrochemicals. To improve our understanding of the catalytic mechanism of HNLs,
      extensive ab initio QM/MM and classical MM molecular dynamics simulations have
      been performed to explore the catalytic conversion of cyanohydrins into aldehyde
      (or ketone) and HCN by hydroxynitrile lyases from Hevea brasiliensis (HbHNLs). It
      was found that the catalytic reaction approximately follows a two-stage
      mechanism. The first stage involves two fast processes including the proton
      abstraction of the substrate through a double-proton transfer and the C-CN bond
      cleavage, while the second stage concerns HCN formation and is rate-determining.
      The complete free energy profile exhibits a peak of ~18 kcal mol(-1).
      Interestingly, the protonation state of Lys236 influences the efficiency of the
      enzyme only to some extent, but it changes the entire catalytic mechanism. The
      dynamical behaviors of substrate delivery and HCN release are basically modulated
      by the gate movement of Trp128. The remarkable exothermicity of substrate binding
      and the facile release of HCN may drive the enzyme-catalyzed reaction to proceed
      along the substrate decomposition efficiently. Computational mutagenesis reveals
      the key residues which play an important role in the catalytic process. 

PMID- 25375266
TI  - Morphological Proof of nerve regeneration after long-term defects of rat sciatic
      nerves.
AB  - Unsatisfactory efficacy of clinical cure for long-term delayed injuries and other
      disadvantages such as the low regeneration rate and speed of axotomized neurons
      and the questionable reinnervation ability of atrophic target organ lead to
      inaction to the long-term delayed injuries. Here we attempted to use autologous
      nerve to bridge a long-term delayed 10-mm defect in SD rats based on some
      previous positive messages of basic and clinical research. In this study, for
      experimental groups, the rat sciatic nerve had been transected leaving a 10-mm
      defect, which was maintained for 3 or 6 months before implantation with the
      autologous graft. The non-grafted animals served as negative control. Measuring
      with electrophysiological and histological techniques, we find: (1) A number of
      long-term axotomized neurons survived and sustained certain degree of axonal
      regenerative capacity; (2) A few denervated Schwann cells survived and retained
      their ability to provide trophic support and myelinate axons in at least 6
      months; (3) the chronically denervated muscle can partially be reinnervated by
      regenerated axons. But the quantity and the quality of the regenerated nerve
      fibers and the reinnervated muscle fibers were all poor. Thus these observations
      provide new positive morphological proof of nerve regeneration after long-term
      defects and further studies will be needed to increase the survival rate and the
      regenerative speed of long-term chronic axotomized neurons, enhance the support
      provided by denervated distal stumps and protect the target muscle. 

PMID- 25375267
TI  - Neuroprotection of nalmefene for postoperative patients with spontaneous
      intracerebral hemorrhage.
AB  - BACKGROUND: Endogenous opiates play an important role in the secondary injury of
      brain tissue after central nervous system injury. It was confirmed that
      nalmefene, an opiates receptor antagonist, has neuroprotective efficacy in animal
      models. However, evidence of nalmefene treatment for surgical patients with
      spontaneous intracerebral hemorrhage is insufficient. METHODS: Outcomes of
      patients treated with nalmefene were retrospectively compared with that of
      patients without any anti-opiate treatment. The primary outcome was functional
      outcome at 6 months post ictus, which was assessed using modified Rankin Scales
      (mRSs). Secondary outcomes included mortality in 30 d post ictus, state of
      consciousness evaluated using Glasgow Coma Scale (GCS) at 1, 3, 7 d post
      operation and complications. RESULTS: Of 79 patients in the nalmefene treatment
      group, 22 (27.85%) had a favorable functional outcome at 6 months, while in the
      control group, 12 of 72 (16.67%) had the same result (p = 0.273). A significantly
      better outcome was observed in the treatment group during only one subgroup
      analyses which was GCS between 3 and 8 (32.26% vs. 6.45%, p = 0.006).
      CONCLUSIONS: Nalmefene treatment was safe for patients with spontaneous
      intracerebral hemorrhage but could not improve the outcome of either short-term
      consciousness or long-term functional outcome.

PMID- 25375268
TI  - How to avoid trivial mistakes during IPG replacement in patients treated with DBS
      for movement disorders: technical note from 13-years experience.
AB  - PURPOSE: Recent data suggest how adverse events occur more frequently after
      Implantable Pulse Generator (IPG) replacement than during the deep electrode
      positioning in patients treated with Deep Brain Stimulation (DBS). For instance,
      erroneous extension adjustment to change in laterality and inaccurate lead
      connection represent problems, which strongly affect patients' outcome. We
      analyzed our data after 13 years of IPG replacement. MATERIALS AND METHODS: We
      treated 107 patients (83 PD and 24 Dystonia) with DBS in 13 years. The Dual
      Channel IPGs replaced during this period were 91. 25 patients needed more than
      one replacement, especially among the dystonic population. During surgery, we
      temporarily marked in all the cases the right extension lead before the
      disconnection from the exhausted IPG. Good impedances were intraoperatively
      checked in all the cases. RESULTS: Our surgical technique allowed us to avoid any
      erroneous change in laterality or abnormal impedances due to a suboptimal
      connection to the IPG. The mean duration of the operation was 25 min and a quick
      postoperative restart of DBS was possible in all the cases. Stability of symptoms
      after IPG replacement was achieved in all the patients, with an accurate clinical
      management within the first 48-72 postoperative hours. CONCLUSION: Our surgical
      and postoperative management demonstrates how to avoid some important adverse
      events with some easy steps, without any discomfort for the patients in terms of
      duration of surgery or longer hospitalization. Thus, stability of symptoms after
      the IPG replacement may be easily guaranteed during the first postoperative
      period.

PMID- 25375269
TI  - Association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T
      polymorphism and ischemic stroke in the Chinese population: a meta-analysis.
AB  - PURPOSE: The association between the methylenetetrahydrofolate reductase (MTHFR)
      gene C677T polymorphism and ischemic stroke (IS) has been extensively studied;
      however, the results from genetic association studies have been inconsistent even
      in the Chinese population. As far as we know, there was no previous meta-analysis
      concerning this association in the Chinese population. Therefore, the aim of our
      meta-analysis was to further evaluate the association in the Chinese population.
      METHODS: We collected all of the relevant studies from Pubmed, OVID, Embase,
      Chinese Wan Fang database, CNKI, Chongqing VIP database and CBM up to August
      2014. The available data was analyzed by Stata (version 12.0). We used odds
      ratios (ORs) and corresponding 95% confidence intervals (CIs) to present the
      strength of the association. Heterogeneity was evaluated by the Q-test and I(2)
      statistic. Different genetic models, subgroup analysis, publication bias and
      sensitivity analysis were used to improve the comprehensive understanding.
      RESULTS: The results showed a significant association between the MTHFR gene
      C677T polymorphism and IS in six genetic models (additive model: OR = 1.34,
      95%CI: 1.17 ~ 1.54, p < 0.001; dominant model: OR = 1.44, 95% CI:1.26 ~ 1.64, p <
      0.001; recessive model: OR = 1.45, 95% CI: 1.15 ~ 1.83, p = 0.001; heterozygote
      model: OR = 1.35, 95% CI: 1.18 ~ 1.55, p < 0.001; homozygote model: OR = 1.80,
      95% CI: 1.34 ~ 2.41, p < 0.001; and allelic model: OR = 1.34, 95% CI: 1.17 ~
      1.53, p < 0.001) based on the overall population, as well as subgroup analysis.
      In addition, the similar results were obtained in the sensitivity analysis based
      on studies with the high quality. CONCLUSIONS: This meta-analysis presented a
      significant association between the MTHFR gene C677T polymorphism and IS, the T
      allele might be a risk factor for IS in the Chinese population.

PMID- 25375270
TI  - Comparing comparators: a look at control arms in kidney cancer studies over the
      years.
AB  - In the past decade, an increasing number of frequently positive randomised
      clinical trials have been completed, allowing new consideration of the present
      therapeutic armamentarium for advanced renal cell carcinoma. These studies were
      predominantly designed to compare the experimental drugs with 1 of 2 active
      control arms: interferon alpha-2a or sorafenib. Different from expectations, the
      final results of some of these studies were not in line with the predictions, and
      the reasons have not been fully investigated. Consequently, there is a great need
      for careful analysis of the studies carried out so far, chiefly the role and
      validity of the control arms. In this regard, the examination of patient baseline
      characteristics and other factors of potential interest seems fundamental for a
      correct analysis of the results of these trials and consequent optimal use of the
      available targeted agents. 

PMID- 25375271
TI  - Interrogation of gossypol therapy in glioblastoma implementing cell line and
      patient-derived tumour models.
AB  - BACKGROUND: Glioblastoma (GBM), being a highly vascularised and locally invasive
      tumour, is an attractive target for anti-angiogenic and anti-invasive therapies.
      The GBM/endothelial cell response to gossypol/temozolomide (TMZ) treatment was
      investigated with a particular aim to assess treatment effects on cancer
      hallmarks. METHODS: Cell viability, endothelial tube formation and GBM tumour
      cell invasion were variously assessed following combined treatment in vitro. The
      U87MG-luc2 subcutaneous xenograft model was used to investigate therapeutic
      response in vivo. Viable tumour response to treatment was interrogated using
      immunohistochemistry. Combined treatment protocols were also tested in primary
      GBM patient-derived cultures. RESULTS: An endothelial/GBM cell viability
      inhibitory effect, as well as an anti-angiogenic and anti-invasive response, to
      combined treatment have been demonstrated in vitro. A significantly greater anti
      proliferative (P=0.020, P=0.030), anti-angiogenic (P=0.040, P<0.0001) and pro
      apoptotic (P=0.0083, P=0.0149) response was observed when combined treatment was
      compared with single gossypol/TMZ treatment response, respectively. GBM cell line
      and patient-specific response to gossypol/TMZ treatment was observed.
      CONCLUSIONS: Our results indicate that response to a combined gossypol/TMZ
      treatment is related to inhibition of tumour-associated angiogenesis, invasion
      and proliferation and warrants further investigation as a novel targeted GBM
      treatment strategy.

PMID- 25375273
TI  - Understanding the adverse effects of ocriplasmin - reply.

PMID- 25375272
TI  - The epithelial alphavbeta3-integrin boosts the MYD88-dependent TLR2 signaling in
      response to viral and bacterial components.
AB  - TLR2 is a cell surface receptor which elicits an immediate response to a wide
      repertoire of bacteria and viruses. Its response is usually thought to be
      proinflammatory rather than an antiviral. In monocytic cells TLR2 cooperates with
      coreceptors, e.g. CD14, CD36 and alphaMbeta2-integrin. In an earlier work we
      showed that alphavbeta3-integrin acts in concert with TLR2 to elicit an innate
      response to HSV, and to lipopolysaccharide. This response is characterized by
      production of IFN-alpha and -beta, a specific set of cytokines, and NF-kappaB
      activation. We investigated the basis of the cooperation between alphavbeta3
      integrin and TLR2. We report that beta3-integrin participates by signaling
      through Y residues located in the C-tail, known to be involved in signaling
      activity. alphavbeta3-integrin boosts the MYD88-dependent TLR2 signaling and
      IRAK4 phosphorylation in 293T and in epithelial, keratinocytic and neuronal cell
      lines. The replication of ICP0minus HSV is greatly enhanced by DN versions of
      MYD88, of Akt - a hub of this pathway, or by beta3integrin-silencing. alphavbeta3
      integrin enables the recruitment of TLR2, MAL, MYD88 at lipid rafts, the
      platforms from where the signaling starts. The PAMP of the HSV-induced innate
      response is the gH/gL virion glycoprotein, which interacts with alphavbeta3
      integrin and TLR2 independently one of the other, and cross-links the two
      receptors. Given the preferential distribution of alphavbeta3-integrin to
      epithelial cells, we propose that alphavbeta3-integrin serves as coreceptor of
      TLR2 in these cells. The results open the possibility that TLR2 makes use of
      coreceptors in a variety of cells to broaden its spectrum of activity and tissue
      specificity. 

PMID- 25375274
TI  - The making of a medical disorder: tracing the emergence of fetal alcohol spectrum
      disorder in Alberta.
AB  - This article examines the processes through which health disorders become
      accepted as a public health concern, and the defining role played by social
      actors responsible for bringing such disorders to public attention. Such analysis
      provides us with a particular history of health disorders and the implications of
      this early history in the current conceptualization of such disorders within
      contemporary health programs and policies. This article traces the emergence and
      acceptance of fetal alcohol spectrum disorder (FASD) as a public health concern
      in Alberta and the ongoing tensions resulting from this early history.
      Specifically, the author examines the integral role of social workers and various
      government officials in getting FASD recognized as a health concern. This Alberta
      case study demonstrates the importance of investigating the sociopolitical
      context in which health disorders emerge and become accepted. 

PMID- 25375276
TI  - Evidence supporting a promotora-delivered entertainment education intervention
      for improving mothers' dietary intake: the Entre Familia: Reflejos de Salud
      Study.
AB  - Entertainment education and the promotora model are 2 evidence-based health
      communication strategies. This study examined their combined effect on promoting
      healthy eating among mothers in a family-based intervention. Participants were
      361 Mexican-origin families living in Imperial County, California, who were
      randomly assigned to an intervention or delayed treatment condition. The
      intervention involved promotoras (community health workers) who delivered 11 home
      visits and 4 telephone calls. Home visits included a 12-minute episode of a 9
      part situation comedy depicting a family struggling with making healthy eating
      choices; an accompanying family workbook was reviewed to build skills and left
      with the family. Baseline and immediate postintervention data were collected from
      the mothers, including the primary outcome of daily servings of fruits and
      vegetables. Other dietary and psychosocial factors related to healthy eating were
      examined. At postintervention, mothers in the intervention reported increases in
      daily vegetable servings (p <= .05); however, no changes were observed in fruit
      consumption. Improvements were observed in behavioral strategies to increase
      fiber (p <= .001) and to decrease fat intake (p <= .001), unhealthy eating
      behaviors (p <= .001), and individual (p <= .05) and family-related (p <= .01)
      perceived barriers to healthy eating. Entertainment education and promotoras
      engaged families and improved mothers' diets. Further research should examine the
      dose needed for greater changes.

PMID- 25375277
TI  - Inflammation and repair in the ischaemic myocardium.
AB  - Shortly after myocardial infarction, various circulating leukocyte subsets
      accumulate in the heart. Leukocyte recruitment is highly coordinated and relies
      on cell production in the bone marrow, mobilization to the blood, and chemokine
      mediated infiltration to the destination tissue. Neutrophils, which are
      phagocytic and inflammatory, are among the first leukocytes to accumulate in
      large numbers. Within a day, neutrophils disappear and are replaced by a subset
      of monocytes that further contribute to inflammation and phagocytosis. After a
      few days, monocyte-derived reparative macrophages accrue, quell inflammation, and
      foster angiogenesis and tissue remodelling. Studies suggest a well-balanced
      response comprising these three waves is essential to optimal infarct healing. 

PMID- 25375275
TI  - Neurocognitive changes after lung transplantation.
AB  - RATIONALE: Neurocognitive impairments are associated with reduced quality of life
      and may adversely affect medical compliance, but their prevalence after lung
      transplantation has not been extensively studied. OBJECTIVES: To examine the
      frequency of neurocognitive impairment after lung transplantation and to examine
      perioperative factors affecting post-transplant neurocognitive function.
      MEASUREMENTS AND MAIN RESULTS: We performed serial assessments of neurocognitive
      function in a consecutive series of 47 subjects who received transplants between
      March 2013 and November 2013 (45% women; mean age, 53.5 +/- 17.2 yr).
      Neurocognitive function was assessed using a composite measure including the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total
      score and Trail Making Test parts A and B obtained before transplant, at hospital
      discharge, and 3 months after discharge. The presence of neurocognitive
      impairment was assessed using the Montreal Cognitive Assessment Battery (MoCA),
      and in-hospital delirium was assessed using the Confusion Assessment Method.
      Results demonstrated that neurocognitive performance initially worsened among non
      cystic fibrosis patients and improved over follow-up (P = 0.002). Time effects
      were strongest on Trail Making Test part B (P < 0.001) and the RBANS (P = 0.054).
      Participants who exhibited delirium during their hospitalization showed poorer
      performance during follow-up assessments (P = 0.006). Examination of cognitive
      impairment rates demonstrated that 21 participants (45%) exhibited neurocognitive
      impairment (MoCA < 26) before lung transplant, whereas 27 (57%) participants
      exhibited impairment after transplantation, and 19 (57%) participants continued
      to neurocognitive impairment during a 3-month follow-up. CONCLUSIONS:
      Neurocognitive impairments are prevalent among lung transplant candidates and
      appear to worsen in some patients after transplant. Delirium during
      hospitalization is associated with worse neurocognitive function after transplant
      among patients without cystic fibrosis.

PMID- 25375279
TI  - [Effectiveness of two aerobic exercise programs in the treatment of metabolic
      syndrome: a preliminary study].
AB  - The effectiveness of two aerobic exercise programs on the modification of the
      metabolic syndrome (MS) components and its influence in reducing cardiovascular
      risk was evaluated in 16 sedentary women (30-66 years old). Patients were
      randomly divided into two exercise groups: continuous training (CE: 45 minutes at
      65-70% of heart rate reserve or HRR) or interval training (IE: 5 x 3 minute
      intervals at 80-85% HRR with two minutes of active recovery at 65-70% HRR), and
      each participant gave previous informed consent. The components of MS were
      assessed according to the criteria for women of the National Cholesterol
      Education/Third Treatment Adult Panel, and cardiovascular risk factors at
      baseline and 16 weeks later. Data analyses were performed with the Wilcoxon
      signed test and the Mann-Whitney U-test (SPSS v. 12.0 Windows: p < 0.05). Both
      exercise programs were effective in the modification of a number of MS components
      (triglycerides, systolic/diastolic blood pressure), however IE had a higher
      percentage of patients without MS diagnosis at the end of the study (62.5%). The
      CE improved the physical fitness by increasing the VO2peak and METs and
      decreasing heart rate recovery, which is reflected on the reduction of
      cardiovascular risk.

PMID- 25375280
TI  - [Transmission of cutaneous leishmaniasis associated with cacao (Theobroma cacao)
      plantations in Tabasco].
AB  - INTRODUCTION: Tabasco is the Mexican state that reported the highest number
      (37.4%) of patients with leishmaniasis during 1990-2011. Close to 90% of these
      patients lived in Chontalpa, where the municipality of Cunduacan accounted for
      the majority of the cases. One of the characteristics of this region is that
      houses are located within cacao plantations. OBJECTIVE: To determine if cacao
      plantations are a risk factor for leishmaniasis transmission in locations of
      Cunduacan, Tabasco. MATERIAL AND METHODS: We performed an analytical and
      retrospective study of 115 locations in Cunduacan, analyzing the number of
      localities with or without patients with leishmaniasis registered between 2000
      2011 and, additionally, if they had cacao plantations, using a map where
      different crops were georeferenced. We measured the magnitude of the association
      (odds ratio, 95% CI). RESULTS: During the period 2000-2011, cases of
      leishmaniasis were reported in 77 (67.0%) Cunduacan locations, of these, 55
      (71.4%) had cocoa plantations, five (6.5%) of banana, five (6.5%) of cane, and 12
      (15.6%) had no crops georeferenced. We found that cocoa crops are a risk factor
      for the transmission of leishmaniasis (OR: 3.438; 95% CI: 1,526-7,742).
      CONCLUSIONS: The probability of transmission of leishmaniasis in areas with cocoa
      crops is greater than in communities without this crop.

PMID- 25375281
TI  - [18F-FDG PET/CT. Its correlation with carcinoembryonic antigen in patients with
      colorectal carcinoma].
AB  - BACKGROUND: 18F-FDG PET has been shown to be highly accurate for recurrent and
      metastatic disease as well as in restaging. The carcinoembryonic antigen (CEA)
      can be used as a marker of prognosis and recurrence. OBJECTIVE: To evaluate the
      association between the presence of lesions detected with 18F-FDG PET/CT and CEA
      values in patients with colorectal carcinoma. MATERIAL AND METHODS: We reviewed
      the records of 2,051 patients who underwent PET/CT to identify all the patients
      with colorectal carcinoma and previous CEA. RESULTS: We included a total of 101
      patients, 51 women and 50 men, with an average age of 60.21 years. The clinical
      stage that prevailed was ECIIA, with moderately differentiated adenocarcinoma
      histology (88.12%). There was agreement between the elevation of CEA and lesions
      detected by PET/CT in 73.9%. From the patients with normal values of CEA, in 42%
      the PET/CT study was positive for tumoral recurrence or metastases. CONCLUSIONS:
      Our study revealed that 18F-FDG PET/CT can provided additional information in up
      to 42% of patients with normal ranges of carcinoembryonic antigen, detecting
      early recurrence or metastases.

PMID- 25375282
TI  - [Deficient prevention and late treatment of diabetic retinopathy in Mexico].
AB  - INTRODUCTION: Retinopathy is a frequent complication of diabetes, causing visual
      impairment in 10% and blindness in 2% of diabetic patients. The aim of this study
      is to describe the clinical profile of diabetic patients in an ophthalmologic
      unit in Tijuana, Mexico. METHODS: Retrospective study of a random sample of 500
      clinical charts of patients with diabetes who attended the Retina Service of
      "Fundacion CODET para la Prevencion de la Ceguera IBP" Ophthalmologic Center
      between 2006 and 2010. RESULTS: The main complaint of 58% of patients was
      decreased visual acuity in first evaluation. Only 6.2% of patients were referred
      by a health professional. Forty-six percent of the patients had a history of
      diabetes of at least 15 years. Thirty percent had clinically significant visual
      impairment at first visit, which was associated with a long history of diabetes
      and previous eye surgery. Twenty-five percent of these patients who were treated
      at our clinic experienced visual deterioration due to advanced retinopathy.
      CONCLUSION: Patients with diabetic retinopathy are referred to ophthalmological
      service tardily, when visual loss is usually severe and irreversible.

PMID- 25375283
TI  - [Study of peripheral nerve injury in trauma patients].
AB  - OBJECTIVE: To determine the prevalence, location, mechanism, and characteristics
      of peripheral nerve injury (PNI) in trauma patients. MATERIAL AND METHODS: A
      retrospective study of medical records with PNI diagnosis secondary to trauma in
      the period of 2008-2012. The following information was collected: gender, age,
      occupation, anatomic location, affected nerve, mechanism of injury, degree of
      injury, costs, and hospitalization time. RESULTS: The prevalence of PNI is 1.12%.
      The location of the nerve injury was 61% upper limb, the highest incidence was
      presented to the brachial plexus (35%) and ulnar nerve (18%). The mechanism of
      the lesion was sharp injury (19%). DISCUSSION: The PNI are commonly present in
      people of a productive age. Neurotmesis was the most frequent degree of lesion.
      The patients stayed at hospital 2.51 +/- 1.29 days and the average cost was
      12,474.00 Mexican pesos +/- 5,595.69 (US$ 1,007.54 +/- 452.21) for one nerve
      injury.

PMID- 25375284
TI  - [Predictors of scoliosis in school-aged children].
AB  - BACKGROUND: Alterations in the spinal column and obesity are on the rise, causing
      great concern in health and educational strata. This paper aims to take a step
      further and study in detail the relationship of the presence of scoliotic hump in
      obese schoolchildren. OBJECTIVE: was to determine the relationship between
      prevalence of types of variables hump and sociodemographic, anthropometric, and
      functional-side dominance. METHODS: The sample consisted of 2,822 schoolchildren
      in Spain, analyzed in 2010 with an average age of 8.5 years (SD: 1.792). Analyzed
      for Adams test, BMI, Edinburgh inventory, deep flexion test, and demographic
      questionnaire, we used the SPSS 20.0 (descriptive and test multivariate binary
      logistic regression). RESULTS: The number of subjects who had scoliosis was 1,023
      (36.3%), obesity occurred in 359 (12.7%) cases, and after regression including
      associations regarding gender, (adjusted OR: 2.044; 1.731-2.413), age (adjusted
      OR: 1.121; 1.070-1.174), presence of obesity (adjusted OR: 0.676; 0.518-0.882),
      and flexibility (adjusted OR: 1.015; 1.001-1.029). CONCLUSIONS: The female
      participants were twice as likely to have hump. The prevalence with respect to
      age indicates that any schoolchild with a year of chronological age has 1.12
      times higher risk of developing hump and subjects carrying the school supplies
      backpack have less risk of hump.

PMID- 25375285
TI  - [Neurological disease surveillance and mandatory reporting: a trend and outcome
      of the national neurological institute of health in mexico city from 2005 to
      2011].
AB  - INTRODUCTION: There is regulated study and mandatory reporting of epidemiological
      surveillance of diseases worldwide. However, it is difficult to observe the
      behavior of conditions especially over time, and especially when it comes to
      diseases that are addressed by their severity in tertiary care units. OBJECTIVE:
      Describe and analyze the behavior of the major communicable neurological diseases
      subject to epidemiological surveillance for a period of seven years in the main
      National Institution of Health that takes in neurological, neurosurgical and
      psychiatric disorders in Mexico. The main conditions that are handled and
      reported were acute inflammatory polyneuropathy (Guillain Barre Syndrome) and
      viral encephalitis, 19.7 and 18.5%, respectively. The condition showing a
      tendency to decrease was neurocysticercosis, and conditions most strongly
      associated with mortality were diseases associated to the human immunodeficiency
      virus and unspecified viral encephalitis. The conditions were more frequent
      especially in men in the age group 25 to 44 years old. It is necessary to stress
      the importance of timely reporting of diseases under epidemiological surveillance
      in Mexico, since knowledge of the behavior of action allows decisions at all
      levels of care.

PMID- 25375286
TI  - [If you drink, don't drive: drunk drivers in Guadalajara and Leon, Mexico].
AB  - OBJECTIVES: To estimate the percentage of drivers of motor vehicles under the
      influence of alcohol circulating during Thursday, Friday, and Saturday night in
      the metropolitan areas of Guadalajara (municipalities Zapopan and Guadalajara)
      and Leon, Mexico, together with their blood alcohol content. To evaluate the
      impact of the Mexican Initiative for Road Safety (IMESEVI, Phase I) in this
      respect. MATERIAL AND METHODS: Drivers who were stopped at sobriety checkpoints
      during the three above-mentioned nights were given an alcohol test together with
      a brief questionnaire that asked for sociodemographic and other background
      variables. The study made use of a pre-post design, with data collections at the
      start of IMESEVI (June 2008) and a year and a half later (February 2010) in the
      metropolitan areas of Guadalajara and Leon. A random sample of 1,299 (pre) and
      2,226 (post) drivers participated in the study. The data analysis was based on a
      hierarchical logistic model for ordinal dependent variables. RESULTS: At
      baseline, the breathalyzer showed a positive result in between 17% (Zapopan) and
      29% (Leon) of the drivers, while between 1-3% exceeded the legal maximum of 0.08
      g/dl for blood alcohol content in Mexico. The night of observation, the presence
      of passengers in the vehicle, as well as the driver's civil state and sex
      affected the probability of a positive result. At the post measurement, the
      probability of a positive result decreased to about a third of the baseline
      measurement. CONCLUSIONS: In view of the evidence that links alcohol with the
      probability of being involved in an accident, drinking and driving prevention
      programs may contribute significantly to better road safety in Mexico.

PMID- 25375287
TI  - [Cancer genomes: where do we go from here?].
AB  - In recent years there has been an exponential growth of knowledge of the
      molecular basis of cancer. In particular, the creation of important initiatives
      for the elucidation of the genomes of several types of cancer has allowed for the
      first time the creation of catalogs for most mutational events in diverse tumors,
      which opens up significant opportunities for oncology and public health. This
      review provides an overview of the progress and possible directions in Mexico. 

PMID- 25375288
TI  - [Treatment of endovascular aneurysms associated with fenestration of the basilar
      artery. A case report].
AB  - The fenestration of the basilar artery is an uncommon anatomical variant that may
      be associated with saccular aneurysms; however this association is rare. We
      report the case of a patient who presented with subarachnoid hemorrhage that was
      successfully treated by coil embolization and review the literature. 

PMID- 25375289
TI  - Eyes on new product development.

PMID- 25375290
TI  - Engineering curvature in graphene ribbons using ultrathin polymer films.
AB  - We propose a method to induce curvature in graphene nanoribbons in a controlled
      manner using an ultrathin thermoset polymer in a bimaterial strip setup and test
      it via molecular dynamics (MD) simulations. Continuum mechanics shows that
      curvature develops to release the residual stress caused by the chemical and
      thermal shrinkage of the polymer during processing and that this curvature
      increases with decreasing film thickness; however, significant deformation is
      only achieved for ultrathin polymer films. Quite surprisingly, explicit MD
      simulations of the curing and annealing processes show that the predicted trend
      not just continues down to film thicknesses of 1-2 nm but that the curvature
      development is enhanced significantly in such ultrathin films due to surface
      tension effects. This combination of effects leads to very large curvatures of
      over 0.14 nm(-1) that can be tuned via film thickness. This provides a new avenue
      to engineer curvature and, thus, electromagnetic properties of graphene. 

PMID- 25375291
TI  - Non-pharmacological interventions for preventing job loss in workers with
      inflammatory arthritis.
AB  - BACKGROUND: Work participation of patients with inflammatory arthritis (IA) is
      important not only economically but also for physical and psychological health.
      There is no Cochrane Review to date on studies of non-pharmacological
      interventions specifically aimed at preventing job loss in people with IA.
      OBJECTIVES: To assess the effects of non-pharmacological interventions that aim
      to prevent job loss, work absenteeism or improve work functioning for employees
      with IA (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic
      arthritis (PsA), other spondylarthritis (SpA) or IA associated with connective
      tissue diseases, such as Systemic Lupus Erythematosus (SLE)). SEARCH METHODS: We
      searched the following databases from inception up to 30 April 2014; The Cochrane
      Library (including Cochrane Central Register of Controlled Trials, i.e. CENTRAL
      and DARE), MEDLINE (PubMed), EMBASE (Embase.com), CINAHL (EbSCOhost),
      ClinicalTrials.gov and PsycINFO (ProQuest). We did not impose language
      restrictions in the search. SELECTION CRITERIA: We included randomised controlled
      trials (RCTs) that evaluated interventions aimed at preventing job loss in adults
      of working age (18 to 65 years) diagnosed with IA, including RA, AS, PsA, SpA or
      other types of IA. Primary outcomes were job loss and sickness absenteeism and
      the secondary outcome was work functioning. DATA COLLECTION AND ANALYSIS: Two
      review authors independently selected trials for inclusion, extracted data and
      assessed risk of bias in the included RCTs. MAIN RESULTS: We included three RCTs
      with a total of 414 participants at risk of job loss. The majority of
      participants had IA, most with RA and to a lesser degree AS. The interventions
      aimed to prevent job loss and improve work functioning in several ways: firstly
      by evaluating work changes or adaptations and secondly by providing any person
      directed interventions including vocational counselling, advice or education.
      Interventions directly targeted at the work environment were minimal and included
      workplace visits (one trial) or any actions by an occupational physician (one
      trial). The duration or dose of the interventions varied from two 1.5-hour
      sessions (one RCT) over five months, two consultation and multidisciplinary
      treatments during three months (one RCT), to six to eight individual or group
      sessions over six months (also one RCT). All participants were recruited through
      rheumatology clinics, both in or outside hospitals. Included trials investigated
      job loss (n = two RCTs; 382 participants), work absenteeism and work functioning
      (n = one RCT; 32 participants). Overall, we evaluated the two smaller trials as
      having a high risk of bias and the large trial as having a low risk of bias.
      Trials showed marked differences in how they performed on risk of bias items,
      particularly on performance bias.We assessed the quality of the evidence using
      the GRADE approach and judged there to be very low quality evidence across the
      three reported outcomes. Of the two RCTs investigating job loss, the larger one
      (n = 242 participants) reported a large statistically significant reduction in
      job loss (relative risk (RR) = 0.35, 95% confidence interval (CI) 0.18 to 0.68)
      and the other RCT (n = 140) reported similar effects in both groups, although the
      CI was very wide (RR = 1.05, 95% CI 0.53 to 2.06). The latter one probably
      suffered from performance bias and we judged it to have a high risk of bias. The
      one small trial investigating sickness absenteeism found uncertain results at six
      months' follow-up (MD = -2.42 days, 95% CI -5.03 to 0.19). Finally, in the same
      small trial investigating work functioning using the Rheumatoid Arthritis-Work
      Instability Scale (RA-WIS), there was a moderate improvement of intermediate term
      work functioning (six months; scale range 0 to 23; mean improvement -4.67 points,
      95% CI -8.43 to -0.91). We identified no adverse effects in the publications of
      the three trials. AUTHORS' CONCLUSIONS: This Cochrane review of three RCTs found
      very low quality evidence overall for job loss prevention interventions having an
      effect on job loss, work absenteeism and work functioning in workers with
      inflammatory arthritis. While this review highlights that further high quality
      RCTs are required, the results suggest that these strategies have potential to be
      effective.

PMID- 25375292
TI  - Recent developments in paper-based microfluidic devices.

PMID- 25375293
TI  - Erosion of bilateral "kissing" ovaries into one large endometrioma.

PMID- 25375294
TI  - The drug scene.

PMID- 25375296
TI  - Cervical insufficiency and cervical cerclage.

PMID- 25375297
TI  - The role of cerclage beyond 24 weeks of gestation.

PMID- 25375298
TI  - Delivery by Caesarean section and infant cardiometabolic status at one year of
      age.
AB  - OBJECTIVE: Disruption of the gut microbiome has been associated with
      overweight/obesity, insulin resistance, and type 2 diabetes. Recently, it has
      been reported that Caesarean section disrupts the normal gut microbiome of
      neonates. As such, these data have raised the intriguing possibility that CS
      could lead to an adverse cardiometabolic risk profile early in life. Thus, we
      sought to compare the cardiometabolic status of infants delivered by CS to that
      of infants delivered vaginally. METHODS: In this prospective observational cohort
      study, 104 women underwent cardiometabolic evaluation in pregnancy followed by
      similar assessment of their infants at one year of age, thereby enabling
      comparison of infants delivered vaginally (n = 74) to those delivered by CS (n =
      30). Infant assessment included anthropometric evaluation and measurement of
      variables associated with cardiometabolic risk. RESULTS: At one year of age,
      there were no differences between infants delivered vaginally and those delivered
      by CS with respect to mean BMI, sum of skinfolds, fasting glucose, insulin
      resistance, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, C
      reactive protein, leptin, and adiponectin, both before and after covariate
      adjustment. Of note, maternal and infant levels of adiponectin (r = 0.31, P =
      0.007) and of total cholesterol, LDL-cholesterol, and HDL-cholesterol (all r >=
      0.23, P < 0.05) were associated in the vaginal delivery group only, whereas the
      analogous association for leptin was observed only in the CS group (r = 0.44, P =
      0.02). CONCLUSION: Caesarean section was not found to be associated with an
      adverse infant cardiometabolic risk profile at one year of age, although it
      potentially may affect the impact of maternal determinants of this profile.

PMID- 25375299
TI  - Uric Acid as a predictor of adverse maternal and perinatal outcomes in women
      hospitalized with preeclampsia.
AB  - OBJECTIVE: Elevated serum uric acid is commonly observed in women with
      preeclampsia, but its utility in predicting adverse outcomes has recently been
      disputed. Our goal was to analyze data from a large cohort of women with
      preeclampsia to determine the utility of serum uric acid in predicting adverse
      maternal and perinatal outcomes. METHODS: Data were obtained from an ongoing
      international prospective study of women admitted to hospital with preeclampsia
      (Pre-eclampsia Integrated Estimate of RiSk). Univariate logistic regression was
      used to determine the relationship between serum uric acid concentration (both
      absolute and gestational-age corrected [Z score]) and adverse outcomes (maternal
      and perinatal). Analyses were conducted to compare cohorts of women with
      preeclampsia as defined by hypertension and proteinuria versus hypertension and
      hyperuricemia. RESULTS: Uric acid Z score was associated with adverse perinatal
      outcome (OR 1.5; 95% CI 1.4 to 1.7) and had a point estimate > 0.7 (area under
      the curve receiver operating characteristic 0.72; 95% CI 0.69 to 0.74). Serum
      uric acid concentration also showed a significant association with adverse
      maternal outcomes, but the point estimate was < 0.7. No significant differences
      were observed between groups in which preeclampsia was defined by hypertension
      and proteinuria and by hypertension and hyperuricemia. CONCLUSION: In women
      admitted to hospital with preeclampsia, the serum uric acid concentration,
      corrected for gestational age via a Z score, is clinically useful in predicting
      adverse perinatal outcomes but not maternal outcomes.

PMID- 25375300
TI  - Changes in smoking during pregnancy in Ontario, 1995 to 2010: results from the
      Canadian community health survey.
AB  - OBJECTIVE: The objectives of this study were (1) to examine changes in smoking
      behaviour across time in pregnant women in Ontario (relative to non-pregnant
      women and men) and (2) to assess whether, among pregnant women, changes across
      time vary as a function of sociodemographic characteristics. METHODS: This study
      used data from the Canadian Community Health Survey. The study sample included 15
      to 49-year-old residents of Ontario. Multivariable logistic regression, with
      interactions between time period and the characteristic of interest, was used to
      examine whether changes varied across time according to (1) group (pregnant
      women, non-pregnant women, men; two-year intervals, 2001 to 2010) and (2)
      pregnant subgroup (maternal age, maternal marital status, maternal education;
      1995 to 2000 [n = 3745], 2001 to 2005 [n = 5084], and 2006 to 2010 [n = 2900]).
      RESULTS: A decrease in the prevalence of smoking across time was seen in all
      groups but was smaller in pregnant women than in non-pregnant women (23.5% vs.
      30.8%). Among pregnant women, interactions between time period and maternal age,
      maternal marital status, and maternal education were statistically significant.
      The prevalence of smoking during pregnancy decreased in older, married, and more
      highly educated women, but increased in younger women (by 8.2%) and less educated
      women (by 12.8%). Although the prevalence of smoking during pregnancy decreased
      in unmarried women, the change was smaller than in married women. CONCLUSION:
      Although the prevalence of smoking in pregnant women is decreasing over time, the
      decrease is smaller than that in non-pregnant women. Pregnant subgroups
      particularly resistant to change include younger, unmarried, and less educated
      mothers. These findings suggest there are subgroups that should be targeted more
      deliberately by public health interventions.

PMID- 25375301
TI  - Is the flexible GnRH antagonist protocol better suited for fresh eSET cycles?
AB  - OBJECTIVE: This study was performed to evaluate the efficacy of the flexible GnRH
      antagonist protocol in comparison with the long GnRH agonist protocol in elective
      single embryo transfer (eSET) practice. It was conducted in a publicly funded in
      vitro fertilization program. METHODS: We performed a prospective cohort analysis
      of data from a private infertility clinic from August 2010 to August 2011. Three
      hundred fourteen women with normal ovarian reserve and undergoing fresh eSET
      cycles were included. Sixty-four women underwent follicular stimulation using a
      flexible GnRH antagonist protocol, and 250 underwent stimulation with a standard
      long mid-luteal GnRH agonist protocol. RESULTS: Implantation rates (35.9% in the
      GnRH antagonist group and 29.6% in the GnRH agonist group, P = 0.5) and ongoing
      pregnancy rates (32.8% in the GnRH antagonist group and 28.8% in the GnRH agonist
      group, P = 0.5) were equivalent in both groups. The duration of stimulation (9.8
      +/- 2 days vs. 10.7 +/- 1.8 days, P < 0.001) and total FSH dose required (2044
      vs. 2775 IU, P < 0.001) were lower in the GnRH antagonist group than in the GnRH
      agonist group. The number of mature oocytes (6.0 vs. 10.0, P < 0. 001) and number
      of embryos (5.0 vs. 7.0, P < 0.001) were also lower in GnRH antagonist group.
      However, the number of embryos cryopreserved was similar in both groups (median
      2.0, P = 0.3). CONCLUSION: In women undergoing in vitro fertilization, the
      flexible GnRH antagonist protocol yields implantation and ongoing pregnancy rates
      that are similar to the long GnRH agonist protocol, and requires lower doses of
      gonadotropins and a shorter duration of treatment. The flexible GnRH antagonist
      protocol appears to be the protocol of choice for an eSET IVF program.

PMID- 25375302
TI  - Are there flaws in the follow-up of women with low-grade cervical dysplasia in
      Ontario?
AB  - BACKGROUND: When cervical cytology screening shows atypical squamous cells of
      unknown significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL),
      and cervical cytology screening has not been performed in the previous year, it
      is recommended that cytology screening be repeated six months later. Women with
      persistent abnormalities should be referred for colposcopy. We explored
      provincial databases in Ontario to determine whether these recommendations were
      always followed. METHODS: Cervical cytology reports in Ontario are contained in a
      provincial database, deterministically linkable to other health services
      databases, including those recording physician reimbursement claims for
      colposcopy. We identified all women in Ontario who had a first time diagnosis of
      ASCUS or LSIL in 2008 or 2009. We searched for additional cytology reports and
      for colposcopy billing claims during the 24 months following the date of the
      first abnormal report. We assessed the interaction of socioeconomic status,
      having abnormal cytology, and having repeat cytology after a report of low-grade
      abnormal cervical cytology. RESULTS: A total of 74 770 women had a first time
      report of low-grade abnormal cytology. Among women with ASCUS and LSIL, 69.7% and
      60.3%, respectively, underwent repeat cytology. Repeat cytology following ASCUS
      disclosed normal (68.2%), ASCUS (19.3%), LSIL (10.6%), and high-grade squamous
      intraepithelial lesion (1.4%); following LSIL, the corresponding percentages were
      48.3%, 18.0%, 30.8%, and 2.6%. Of women with ASCUS, 16.2% went directly for
      colposcopy; 14.0% did not repeat cytology or go for colposcopy. Of women with
      LSIL, 26.4% went directly for colposcopy but 13.4% had no follow-up. CONCLUSION:
      We have demonstrated the potential for substantial improvement in cervical
      cytology six months after a finding of ASCUS and LSIL. We found that many women
      with ASCUS and LSIL had unnecessary referrals directly for colposcopy, and we
      identified a lack of follow-up for one sixth of women with low-grade abnormal
      cytology.

PMID- 25375303
TI  - Collection of 125 oocytes in an in vitro maturation cycle using a new oocyte
      collection technique: a case report.
AB  - BACKGROUND: We have developed a new oocyte collection technique applicable to use
      in women with "string-of-pearls" polycystic ovaries undergoing in vitro
      maturation (IVM) of oocytes for in vitro fertilization. CASE: A 34-year-old woman
      with polycystic ovary syndrome and infertility underwent IVM. Her ovaries had the
      string-of-pearls appearance on ultrasound, and antral follicle counts were
      consistently less than 60. An IVM cycle was performed using a new "rapid-pass"
      oocyte collection technique. We retrieved 125 germinal vesicle oocytes. A total
      of 44 oocytes reached the metaphase II stage after 48 hours in culture. After
      fertilization, four embryos were transferred to the uterus, resulting in a live
      birth. CONCLUSION: We believe this to be the largest number of oocytes retrieved
      from a single individual at one time. This was done using a newly developed
      aspiration technique.

PMID- 25375304
TI  - Recurrence of carcinoma of appendix presenting as vulvar swelling: a case report.
AB  - BACKGROUND: Adenocarcinoma of the vulva is rare and can develop as metastatic
      recurrence originating from the appendix. Vulvar swelling can be one of the
      presenting symptoms and should not be presumed to be lymphedema unless possible
      malignant metastasis has been excluded. CASE: We report a case of vulvar swelling
      arising after hysterectomy, bilateral salpingo-oophorectomy, pelvic and para
      aotic lymphadenectomy, and appendectomy for presumed ovarian malignancy.
      Pathology revealed stage IV carcinoma of the appendix. The patient presented with
      vulvar swelling 12 months after the operation. An erythematous vulva with
      multiple hard nodular growths was found on examination. Biopsy confirmed
      recurrence of adenocarcinoma of the appendix. CONCLUSION: Recurrent carcinoma of
      the appendix can metastasize to the vulva and may present as vulvar swelling.

PMID- 25375305
TI  - Physician liability and non-invasive prenatal testing.
AB  - Although non-invasive prenatal testing (NIPT) marks a notable development in the
      field of prenatal genetic testing, there are some physician liability
      considerations raised by this technology. As NIPT is still emerging as the
      standard of care and is just starting to receive provincial funding, the question
      arises of whether physicians are obligated to disclose the availability of NIPT
      to eligible patients as part of the physician-patient discussion about prenatal
      screening and diagnosis. If NIPT is discussed with patients, it is important to
      disclose the limitations of this technology with respect to its accuracy and the
      number of disorders that it can detect when compared with invasive diagnostic
      options. A failure to sufficiently disclose these limitations could leave
      patients with false assurances about the health of their fetuses and could raise
      informed consent and liability issues, particularly if a child is born with a
      disability as a result. 

PMID- 25375306
TI  - Menstrual suppression in special circumstances.
AB  - OBJECTIVE: To provide a Canadian consensus document for health care providers
      with recommendations for menstrual suppression in patients with physical and/or
      cognitive challenges or those who are undergoing cancer treatment in whom
      menstruation may have a deleterious effect on their health. OPTIONS: This
      document reviews the options available for menstrual suppression, its specific
      indications, contraindications, and side effects, both immediate and long-term,
      and the investigations and monitoring necessary throughout suppression. OUTCOMES:
      Clinicians will be better informed about the options and indications for
      menstrual suppression in patients with cognitive and/or physical disabilities and
      patients undergoing chemotherapy, radiation, or other treatments for cancer.
      EVIDENCE: Published literature was retrieved through searches of Medline, EMBASE,
      OVID, and the Cochrane Library using appropriate controlled vocabulary and key
      words (heavy menstrual bleeding, menstrual suppression, chemotherapy/radiation,
      cognitive disability, physical disability, learning disability). Results were
      restricted to systematic reviews, randomized controlled trials, observation
      studies, and pilot studies. There were no language or date restrictions. Searches
      were updated on a regular basis and new material was incorporated into the
      guideline until September 2013. Grey (unpublished) literature was identified
      through searching 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 was rated using the criteria described in the Report of
      the Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND
      COSTS: There is a need for specific guidelines on menstrual suppression in at
      risk populations for health care providers. Recommendations 1. Menstrual
      suppression and therapeutic amenorrhea should be considered safe and viable
      options for women who need or want to have fewer or no menses. (II-2A) 2.
      Menstrual suppression should not be initiated in young women with developmental
      disabilities until after the onset of menses. (II-2B) 3. Combined hormonal or
      progesterone-only products can be used in an extended or continuous manner to
      obtain menstrual suppression. (I-A) 4. Gynaecologic consultation should be
      considered prior to the initiation of treatment in all premenopausal women at
      risk for abnormal uterine bleeding from chemotherapy. (II-1A) 5. Leuprolide
      acetate or combined hormonal contraception should be considered highly effective
      in preventing abnormal uterine bleeding when initiated prior to cancer treatment
      in premenopausal women at risk for thrombocytopenia. (II-2A).

PMID- 25375308
TI  - Assessment of methane emissions from oil and gas production pads using mobile
      measurements.
AB  - A new mobile methane emissions inspection approach, Other Test Method (OTM) 33A,
      was used to quantify short-term emission rates from 210 oil and gas production
      pads during eight two-week field studies in Texas, Colorado, and Wyoming from
      2010 to 2013. Emission rates were log-normally distributed with geometric means
      and 95% confidence intervals (CIs) of 0.33 (0.23, 0.48), 0.14 (0.11, 0.19), and
      0.59 (0.47, 0.74) g/s in the Barnett, Denver-Julesburg, and Pinedale basins,
      respectively. This study focused on sites with emission rates above 0.01 g/s and
      included short-term (i.e., condensate tank flashing) and maintenance-related
      emissions. The results fell within the upper ranges of the distributions observed
      in recent onsite direct measurement studies. Considering data across all basins,
      a multivariate linear regression was used to assess the relationship of methane
      emissions to well age, gas production, and hydrocarbon liquids (oil or
      condensate) production. Methane emissions were positively correlated with gas
      production, but only approximately 10% of the variation in emission rates was
      explained by variation in production levels. The weak correlation between
      emission and production rates may indicate that maintenance-related stochastic
      variables and design of production and control equipment are factors determining
      emissions. 

PMID- 25375307
TI  - Prenatal screening, diagnosis, and pregnancy management of fetal neural tube
      defects.
AB  - OBJECTIVE: To provide obstetrical and genetic health care practitioners with
      guidelines and recommendations for prenatal screening, diagnosis, and obstetrical
      management of fetal open and closed neural tube defects (OCNTD). OPTIONS: This
      review includes prenatal screening and diagnostic techniques currently being used
      for the detection of OCNTD including maternal serum alpha fetoprotein screening,
      ultrasound, fetal magnetic resonance imaging, and amniocentesis. OUTCOMES: To
      improve prenatal screening, diagnosis, and obstetrical management of OCNTD while
      taking into consideration patient care, efficacy, cost, and care procedures.
      EVIDENCE: Published literature was retrieved through searches of PubMed or
      MEDLINE, CINAHL, and The Cochrane Library in November, 2013, using appropriate
      controlled vocabulary and key words (e.g., prenatal screening, congenital
      anomalies, neural tube defects, alpha fetoprotein, ultrasound scan, magnetic
      resonance imaging). Results were restricted to systematic reviews, randomized
      control trials/controlled clinical trials, and observational studies published in
      English from 1977 to 2012. Searches were updated on a regular basis and
      incorporated in the guideline to November 30, 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. An online survey of health care practitioners was also reviewed.
      VALUES: The quality of evidence in this document was rated using the criteria
      described in the Report of the Canadian Task Force on Preventive Health Care
      (Table). BENEFITS, HARMS, AND COSTS: This review will provide health care
      practitioners with a better understanding of the available prenatal screening
      methods for OCNTD and the benefits and risks associated with each technique to
      allow evidenced-based decisions on OCNTD screening, diagnosis, and obstetrical
      management.

PMID- 25375309
TI  - Ca12InC13-x and Ba12InC18H4: alkaline-earth indium allenylides synthesized in
      AE/Li flux (AE = Ca, Ba).
AB  - Two new complex main-group metal carbides were synthesized from reactions of
      indium, carbon, and a metal hydride in metal flux mixtures of an alkaline earth
      (AE = Ca, Ba) and lithium. Ca(12)InC(13-x) and Ba(12)InC(18)H(4) both crystallize
      in cubic space group Im3 [a = 9.6055(8) and 11.1447(7) A, respectively]. Their
      related structures are both built on a body-centered-cubic array of icosahedral
      clusters comprised of an indium atom and 12 surrounding alkaline-earth cations;
      these clusters are connected by bridging monatomic anions (either H(-) or C(4-))
      and allenylide anions, C(3)(4-). The allenylide anions were characterized by
      Raman spectroscopy and hydrolysis studies. Density of states and crystal orbital
      Hamilton population calculations confirm that both compounds are metallic.

PMID- 25375310
TI  - Designing smarter pay-for-performance programs.

PMID- 25375311
TI  - Surgical Pleth Index guided analgesia blunts the intraoperative sympathetic
      response to laparoscopic cholecystectomy.
AB  - BACKGROUND: Surgical noxious stimuli generate a stress response with an increased
      sympathetic activity, potentially affecting the perioperative outcome. Surgical
      Pleth Index (SPI), derived from the pulse plethysmogram, has been proposed as a
      tool to assess nociception-antinociception balance. The relationship between SPI
      and autonomic nervous system (ANS) during general anesthesia is poorly understood
      and it is doubtful if SPI-guided analgesia may offer advantages over the standard
      clinical practice. The study was designed to evaluate if SPI-guided analgesia
      leads to a lower sympathetic modulation compared with standard clinical practice.
      METHODS: Electrocardiographic wave, non-invasive blood pressure and SPI were
      recorded in ASA I-II patients undergoing elective laparoscopic cholecystectomy,
      randomized to receive SPI-guided analgesia or standard analgesia. Hemodynamic
      parameters, SPI, mean and variance of heart rate, low (LF) and high frequency
      (HF) spectral components of heart rate variability were measured at four time
      points: (T0) baseline, (T1) after induction of general anesthesia, (T2) after
      pneumoperitoneum insufflation and (T3) after pneumoperitoneum withdrawal.
      RESULTS: SPI, hemodynamic and ANS parameters changed significantly in both groups
      during the study period (P<0.0001). At T2 SPI and markers of sympathetic
      modulation were significantly lower in SPI group (mean [SD] SPI 38.1 [15.3] vs.
      48.1 [16.2] normalized units, P<0.05; LF 38 [8.6] vs. 56.2 [20.6] normalized
      units, P<0.01; LF/HF 1.01 [1.1] vs. 2.68 [2.07], P<0.01). There was no difference
      in remifentanil consumption, recovery time from anesthesia, or postoperative pain
      and complications. CONCLUSION: SPI-guided analgesia led to a more stable
      sympathetic modulation but didn't seem to offer clinically relevant advantages
      over the standard clinical practice for laparoscopic cholecystectomy.

PMID- 25375312
TI  - Confirmation of correct central venous catheter position in the preoperative
      setting by echocardiographic "bubble-test".
AB  - BACKGROUND: Verification of the central venous catheters (CVCs) position by chest
      X-ray (CXR) is usually performed in the postoperative period with the risk
      related to possible malposition. This prospective observational study aimed to
      assess the diagnostic accuracy and reproducibility of ultrasound (US) and "bubble
      test" to detect malpositions of CVC in the preoperative setting. METHODS: The
      study included 105 patients undergoing preoperative CVC placement. A US protocol
      aimed at direct visualization of the CVC was completed by a single operator and
      two consecutive "bubble tests" were performed independently by different
      physicians. Two parameters were considered: complete right atrium (RA)
      opacization versus visualization of "no or few bubbles" and time from agitated
      saline injection to visualization of micro-bubbles in the RA ("push-to-bubbles"
      time). RESULTS: CXR identified 14 (13%) CVC malpositions. Vascular US showed a
      sensitivity of 64% and a specificity of 100% while visualization of "no or few
      bubbles" at bubble test yielded a sensitivity of 50% and a specificity of 100%.
      "Push-to-bubbles" times were ~9 times longer in patients with compared to those
      without CVC malposition (1400 [702-2160] ms versus 167 [123-228] ms, P<0.001). A
      cut off value of 500 ms had a sensitivity of 100% and a specificity of 99% for
      CVC malposition with an inter-observer agreement of 99% (kappa 0.96, P<0.001).
      CONCLUSION: CVC malposition was observed in a sizeable proportion of patients
      undergoing preoperative central venous cannulation. Measurement of "push-to
      bubbles" time is a fast, accurate and highly reproducible tool for verifying the
      correct CVC position.

PMID- 25375313
TI  - Preventing hospital malnutrition: a survey on nutritional policies in an Italian
      University Hospital.
AB  - BACKGROUND: A proper strategy for fighting hospital malnutrition should include
      nutritional screening of all hospitalized patients, adequate utilization of the
      Hospital facilities - such as Clinical Nutrition Services or Nutrition Teams -
      and an adequate algorithm for the adoption of proper nutrition support (oral,
      enteral or parenteral) with proper timing. The main aim of the present study was
      to investigate the current policies of different non-intensive wards of our
      institution (a 1100 beds University Hospital) in terms of prevention of hospital
      malnutrition. METHODS: We conducted a one-day survey to verify the current
      policies of nutritional screening and the indication to nutritional support in
      adult patients, interviewing nurses and physicians of our non-intensive hospital
      wards. RESULTS: A total of 29 wards were considered, which sum up to 755
      hospitalized patients. We found that nutritional screening at admission is
      routinely assessed only in 41% of wards and that oral nutrient intake is
      controlled regularly only in 72%. Indication to clinical nutrition support and
      specifically to artificial nutrition is not consistent with the current
      international guidelines. Only 14% of patients were receiving artificial
      nutrition at the moment of the survey and the majority of them were given
      parenteral nutrition rather than enteral feeding. CONCLUSION: Our survey
      confirmed that in large hospitals the main barriers to the fight against hospital
      malnutrition are the lack of knowledge and/or commitment by nurses and physicians
      as well as the lack of well-defined hospital policies on early nutritional
      screening, surveillance of nutritional status and indication to nutrition
      support.

PMID- 25375314
TI  - Endotracheal tubes cuff pressure control: does the CO2 matter?

PMID- 25375315
TI  - A meta-analysis of unilateral versus bilateral pedicle screw fixation in
      minimally invasive lumbar interbody fusion.
AB  - STUDY DESIGN: Meta-analysis. BACKGROUND: Bilateral pedicle screw fixation (PS)
      after lumbar interbody fusion is a widely accepted method of managing various
      spinal diseases. Recently, unilateral PS fixation has been reported as effective
      as bilateral PS fixation. This meta-analysis aimed to comparatively assess the
      efficacy and safety of unilateral PS fixation and bilateral PS fixation in the
      minimally invasive (MIS) lumbar interbody fusion for one-level degenerative
      lumbar spine disease. METHODS: MEDLINE/PubMed, EMBASE, BIOSIS Previews, and
      Cochrane Library were searched through March 30, 2014. Randomized controlled
      trials (RCTs) and controlled clinical trials (CCTs) on unilateral versus
      bilateral PS fixation in MIS lumbar interbody fusion that met the inclusion
      criteria and the methodological quality standard were retrieved and reviewed.
      Data on participant characteristics, interventions, follow-up period, and
      outcomes were extracted from the included studies and analyzed by Review Manager
      5.2. RESULTS: Six studies (5 RCTs and 1 CCT) involving 298 patients were
      selected. There were no significant differences between unilateral and bilateral
      PS fixation procedures in fusion rate, complications, visual analogue score (VAS)
      for leg pain, VAS for back pain, Oswestry disability index (ODI). Both fixation
      procedures had similar length of hospital stay (MD = 0.38, 95% CI = -0.83 to
      1.58; P = 0.54). In contrast, bilateral PS fixation was associated with
      significantly more intra-operative blood loss (P = 0.002) and significantly
      longer operation time (P = 0.02) as compared with unilateral PS fixation.
      CONCLUSIONS: Unilateral PS fixation appears as effective and safe as bilateral PS
      fixation in MIS lumbar interbody fusion but requires less operative time and
      causes less blood loss, thus offering a simple alternative approach for one-level
      lumbar degenerative disease.

PMID- 25375316
TI  - A comprehensive study of extended tetrathiafulvalene cruciform molecules for
      molecular electronics: synthesis and electrical transport measurements.
AB  - Cruciform-like molecules with two orthogonally placed pi-conjugated systems have
      in recent years attracted significant interest for their potential use as
      molecular wires in molecular electronics. Here we present synthetic protocols for
      a large selection of cruciform molecules based on oligo(phenyleneethynylene)
      (OPE) and tetrathiafulvalene (TTF) scaffolds, end-capped with acetyl-protected
      thiolates as electrode anchoring groups. The molecules were subjected to a
      comprehensive study of their conducting properties as well as their photophysical
      and electrochemical properties in solution. The complex nature of the molecules
      and their possible binding in different configurations in junctions called for
      different techniques of conductance measurements: (1) conducting-probe atomic
      force microscopy (CP-AFM) measurements on self-assembled monolayers (SAMs), (2)
      mechanically controlled break-junction (MCBJ) measurements, and (3) scanning
      tunneling microscopy break-junction (STM-BJ) measurements. The CP-AFM
      measurements showed structure-property relationships from SAMs of series of OPE3
      and OPE5 cruciform molecules; the conductance of the SAM increased with the
      number of dithiafulvene (DTF) units (0, 1, 2) along the wire, and it increased
      when substituting two arylethynyl end groups of the OPE3 backbone with two DTF
      units. The MCBJ and STM-BJ studies on single molecules both showed that DTFs
      decreased the junction formation probability, but, in contrast, no significant
      influence on the single-molecule conductance was observed. We suggest that the
      origins of the difference between SAM and single-molecule measurements lie in the
      nature of the molecule-electrode interface as well as in effects arising from
      molecular packing in the SAMs. This comprehensive study shows that for complex
      molecules care should be taken when directly comparing single-molecule
      measurements and measurements of SAMs and solid-state devices thereof. 

PMID- 25375317
TI  - Exceptionally mild palladium(II)-catalyzed dehydrogenative C-H/C-H arylation of
      indolines at the C-7 position under air.
AB  - An improved method for the dehydrogenative C-H/C-H cross-coupling at the C-7
      position of indolines containing a urea as a directing group is reported. The new
      protocol is a rare example of an aerobic palladium(II)-catalyzed cross
      dehydrogenative coupling (CDC) reaction that proceeds at low temperature. The use
      of either Cu(OAc)2 in an open flask or dioxygen (balloon) at 50  degrees C
      tolerates indolines not substituted at C-2 and C-3, thereby extending the scope
      of the previous method that suffers from indoline-to-indole oxidation. 

PMID- 25375322
TI  - Engineering attenuated virulence of a Theileria annulata-infected macrophage.
AB  - Live attenuated vaccines are used to combat tropical theileriosis in North
      Africa, the Middle East, India, and China. The attenuation process is empirical
      and occurs only after many months, sometimes years, of in vitro culture of
      virulent clinical isolates. During this extensive culturing, attenuated lines
      lose their vaccine potential. To circumvent this we engineered the rapid ablation
      of the host cell transcription factor c-Jun, and within only 3 weeks the line
      engineered for loss of c-Jun activation displayed in vitro correlates of
      attenuation such as loss of adhesion, reduced MMP9 gelatinase activity, and
      diminished capacity to traverse Matrigel. Specific ablation of a single infected
      host cell virulence trait (c-Jun) induced a complete failure of Theileria
      annulata-transformed macrophages to disseminate, whereas virulent macrophages
      disseminated to the kidneys, spleen, and lungs of Rag2/gammaC mice. Thus, in this
      heterologous mouse model loss of c-Jun expression led to ablation of
      dissemination of T. annulata-infected and transformed macrophages. The generation
      of Theileria-infected macrophages genetically engineered for ablation of a
      specific host cell virulence trait now makes possible experimental vaccination of
      calves to address how loss of macrophage dissemination impacts the disease
      pathology of tropical theileriosis. 

PMID- 25375323
TI  - Prediction of interactions between viral and host proteins using supervised
      machine learning methods.
AB  - BACKGROUND: Viral-host protein-protein interaction plays a vital role in
      pathogenesis, since it defines viral infection of the host and regulation of the
      host proteins. Identification of key viral-host protein-protein interactions
      (PPIs) has great implication for therapeutics. METHODS: In this study, a
      systematic attempt has been made to predict viral-host PPIs by integrating
      different features, including domain-domain association, network topology and
      sequence information using viral-host PPIs from VirusMINT. The three well-known
      supervised machine learning methods, such as SVM, Naive Bayes and Random Forest,
      which are commonly used in the prediction of PPIs, were employed to evaluate the
      performance measure based on five-fold cross validation techniques. RESULTS: Out
      of 44 descriptors, best features were found to be domain-domain association and
      methionine, serine and valine amino acid composition of viral proteins. In this
      study, SVM-based method achieved better sensitivity of 67% over Naive Bayes
      (37.49%) and Random Forest (55.66%). However the specificity of Naive Bayes was
      the highest (99.52%) as compared with SVM (74%) and Random Forest (89.08%).
      Overall, the SVM and Random Forest achieved accuracy of 71% and 72.41%,
      respectively. The proposed SVM-based method was evaluated on blind dataset and
      attained a sensitivity of 64%, specificity of 83%, and accuracy of 74%. In
      addition, unknown potential targets of hepatitis B virus-human and hepatitis E
      virus-human PPIs have been predicted through proposed SVM model and validated by
      gene ontology enrichment analysis. Our proposed model shows that, hepatitis B
      virus "C protein" binds to membrane docking protein, while "X protein" and "P
      protein" interacts with cell-killing and metabolic process proteins,
      respectively. CONCLUSION: The proposed method can predict large scale
      interspecies viral-human PPIs. The nature and function of unknown viral proteins
      (HBV and HEV), interacting partners of host protein were identified using
      optimised SVM model.

PMID- 25375327
TI  - Uncal herniation in a fully conscious patient-The sliding uncus syndrome.
AB  - Uncal herniation is accompanied by a decreased level of consciousness. We
      describe a patient who remained fully alert despite the uncal herniation. The
      computed tomography (CT) scans allowed us to visualize the uncus and its spatial
      relation to the cerebral peduncle. We describe the sliding uncus syndrome. 

PMID- 25375326
TI  - Discovery and characterization of a potent and selective inhibitor of Aedes
      aegypti inward rectifier potassium channels.
AB  - Vector-borne diseases such as dengue fever and malaria, which are transmitted by
      infected female mosquitoes, affect nearly half of the world's population. The
      emergence of insecticide-resistant mosquito populations is reducing the
      effectiveness of conventional insecticides and threatening current vector control
      strategies, which has created an urgent need to identify new molecular targets
      against which novel classes of insecticides can be developed. We previously
      demonstrated that small molecule inhibitors of mammalian Kir channels represent
      promising chemicals for new mosquitocide development. In this study, high
      throughput screening of approximately 30,000 chemically diverse small-molecules
      was employed to discover potent and selective inhibitors of Aedes aegypti Kir1
      (AeKir1) channels heterologously expressed in HEK293 cells. Of 283 confirmed
      screening 'hits', the small-molecule inhibitor VU625 was selected for lead
      optimization and in vivo studies based on its potency and selectivity toward
      AeKir1, and tractability for medicinal chemistry. In patch clamp
      electrophysiology experiments of HEK293 cells, VU625 inhibits AeKir1 with an IC50
      value of 96.8 nM, making VU625 the most potent inhibitor of AeKir1 described to
      date. Furthermore, electrophysiology experiments in Xenopus oocytes revealed that
      VU625 is a weak inhibitor of AeKir2B. Surprisingly, injection of VU625 failed to
      elicit significant effects on mosquito behavior, urine excretion, or survival.
      However, when co-injected with probenecid, VU625 inhibited the excretory capacity
      of mosquitoes and was toxic, suggesting that the compound is a substrate of
      organic anion and/or ATP-binding cassette (ABC) transporters. The dose-toxicity
      relationship of VU625 (when co-injected with probenecid) is biphasic, which is
      consistent with the molecule inhibiting both AeKir1 and AeKir2B with different
      potencies. This study demonstrates proof-of-concept that potent and highly
      selective inhibitors of mosquito Kir channels can be developed using conventional
      drug discovery approaches. Furthermore, it reinforces the notion that the
      physical and chemical properties that determine a compound's bioavailability in
      vivo will be critical in determining the efficacy of Kir channel inhibitors as
      insecticides. 

PMID- 25375324
TI  - Coronavirus cell entry occurs through the endo-/lysosomal pathway in a
      proteolysis-dependent manner.
AB  - Enveloped viruses need to fuse with a host cell membrane in order to deliver
      their genome into the host cell. While some viruses fuse with the plasma
      membrane, many viruses are endocytosed prior to fusion. Specific cues in the
      endosomal microenvironment induce conformational changes in the viral fusion
      proteins leading to viral and host membrane fusion. In the present study we
      investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we
      found that proteins known to be important for late endosomal maturation and
      endosome-lysosome fusion profoundly promote infection of cells with mouse
      hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as
      well as a novel, replication-independent fusion assay we confirmed the importance
      of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to
      lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV
      was shown to be less sensitive to perturbation of endosomal pH than vesicular
      stomatitis virus and influenza A virus, which fuse in early and late endosomes,
      respectively. Our results indicate that entry of MHV depends on proteolytic
      processing of its fusion protein S by lysosomal proteases. Fusion of MHV was
      severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of
      MHV to lysosomes and processing by lysosomal proteases was no longer required
      when a furin cleavage site was introduced in the S protein immediately upstream
      of the fusion peptide. Also entry of feline CoV was shown to depend on
      trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS
      CoV, which contains a minimal furin cleavage site just upstream of the fusion
      peptide, was negatively affected by inhibition of furin, but not of lysosomal
      proteases. We conclude that a proteolytic cleavage site in the CoV S protein
      directly upstream of the fusion peptide is an essential determinant of the
      intracellular site of fusion. 

PMID- 25375328
TI  - Trans-national scale-up of services in global health.
AB  - BACKGROUND: Scaling up innovative healthcare programs offers a means to improve
      access, quality, and health equity across multiple health areas. Despite large
      numbers of promising projects, little is known about successful efforts to scale
      up. This study examines trans-national scale, whereby a program operates in two
      or more countries. Trans-national scale is a distinct measure that reflects
      opportunities to replicate healthcare programs in multiple countries, thereby
      providing services to broader populations. METHODS: Based on the Center for
      Health Market Innovations (CHMI) database of nearly 1200 health programs, the
      study contrasts 116 programs that have achieved trans-national scale with 1,068
      single-country programs. Data was collected on the programs' health focus,
      service activity, legal status, and funding sources, as well as the programs'
      locations (rural v. urban emphasis), and founding year; differences are reported
      with statistical significance. FINDINGS: This analysis examines 116 programs that
      have achieved trans-national scale (TNS) across multiple disease areas and
      activity types. Compared to 1,068 single-country programs, we find that trans
      nationally scaled programs are more donor-reliant; more likely to focus on
      targeted health needs such as HIV/AIDS, TB, malaria, or family planning rather
      than provide more comprehensive general care; and more likely to engage in
      activities that support healthcare services rather than provide direct clinical
      care. CONCLUSION: This work, based on a large data set of health programs,
      reports on trans-national scale with comparison to single-country programs. The
      work is a step towards understanding when programs are able to replicate their
      services as they attempt to expand health services for the poor across countries
      and health areas. A subset of these programs should be the subject of case
      studies to understand factors that affect the scaling process, particularly
      seeking to identify mechanisms that lead to improved health outcomes.

PMID- 25375329
TI  - Satellite tagging and biopsy sampling of killer whales at subantarctic Marion
      Island: effectiveness, immediate reactions and long-term responses.
AB  - Remote tissue biopsy sampling and satellite tagging are becoming widely used in
      large marine vertebrate studies because they allow the collection of a diverse
      suite of otherwise difficult-to-obtain data which are critical in understanding
      the ecology of these species and to their conservation and management.
      Researchers must carefully consider their methods not only from an animal welfare
      perspective, but also to ensure the scientific rigour and validity of their
      results. We report methods for shore-based, remote biopsy sampling and satellite
      tagging of killer whales Orcinus orca at Subantarctic Marion Island. The
      performance of these methods is critically assessed using 1) the attachment
      duration of low-impact minimally percutaneous satellite tags; 2) the immediate
      behavioural reactions of animals to biopsy sampling and satellite tagging; 3) the
      effect of researcher experience on biopsy sampling and satellite tagging; and 4)
      the mid- (1 month) and long- (24 month) term behavioural consequences. To study
      mid- and long-term behavioural changes we used multievent capture-recapture
      models that accommodate imperfect detection and individual heterogeneity. We made
      72 biopsy sampling attempts (resulting in 32 tissue samples) and 37 satellite
      tagging attempts (deploying 19 tags). Biopsy sampling success rates were low
      (43%), but tagging rates were high with improved tag designs (86%). The improved
      tags remained attached for 26+/-14 days (mean +/- SD). Individuals most often
      showed no reaction when attempts missed (66%) and a slight reaction-defined as a
      slight flinch, slight shake, short acceleration, or immediate dive-when hit
      (54%). Severe immediate reactions were never observed. Hit or miss and age-sex
      class were important predictors of the reaction, but the method (tag or biopsy)
      was unimportant. Multievent trap-dependence modelling revealed considerable
      variation in individual sighting patterns; however, there were no significant mid
      or long-term changes following biopsy sampling or tagging. 

PMID- 25375330
TI  - Preparation of risedronate nanoparticles by solvent evaporation technique.
AB  - One approach for the enhancement of oral drug bioavailability is the technique of
      nanoparticle preparation. Risedronate sodium (Biopharmaceutical Classification
      System Class III) was chosen as a model compound with high water solubility and
      low intestinal permeability. Eighteen samples of risedronate sodium were prepared
      by the solvent evaporation technique with sodium dodecyl sulfate, polysorbate,
      macrogol, sodium carboxymethyl cellulose and sodium carboxymethyl dextran as
      nanoparticle stabilizers applied in three concentrations. The prepared samples
      were characterized by dynamic light scattering and scanning electron microscopy.
      Fourier transform mid-infrared spectroscopy was used for verification of the
      composition of the samples. The particle size of sixteen samples was less than
      200 nm. Polysorbate, sodium carboxymethyl dextran and macrogol were determined as
      the most favourable excipients; the particle size of the samples of risedronate
      with these excipients ranged from 2.8 to 10.5 nm. 

PMID- 25375331
TI  - Chemical constituents of kino extract from Corymbia torelliana.
AB  - Seven flavanones were identified from kino exudate of Corymbia torelliana by
      spectroscopic and spectrometric methods including UV, 1D and 2D NMR and UPLC-HR
      MS. The study identified seven molecules, namely 3,4',5,7-tetrahydroxyflavanone
      (1), 3',4',5,7-tetrahydroxyflavanone (2), 4',5,7-trihydroxyflavanone (3), 3,4',5
      trihydroxy-7-methoxyflavanone (4), (+)-(2S)-4',5,7-trihydroxy-6-methylflavanone
      (5), 4',5,7-trihydroxy-6,8-dimethylflavanone (6) and 4',5-dihydroxy-7
      methoxyflavanone (7) from this eucalypt species. This is the first report of
      these natural products from C. torelliana kino exudate. 

PMID- 25375332
TI  - RNA/aTNA chimeras: RNAi effects and nucleases resistance of single and double
      stranded RNAs.
AB  - The RNA interference pathway (RNAi) is a specific and powerful biological
      process, triggered by small non-coding RNA molecules and involved in gene
      expression regulation. In this work, we explored the possibility of increasing
      the biological stability of these RNA molecules by replacing their natural ribose
      ring with an acyclic L-threoninol backbone. In particular, this modification has
      been incorporated at certain positions of the oligonucleotide strands and its
      effects on the biological properties of the siRNA have been evaluated. In vitro
      cellular RNAi assays have demonstrated that the L-threoninol backbone is well
      tolerated by the RNAi machinery in both double and single-stranded fashion, with
      activities significantly higher than those evinced by the unmodified RNAs and
      comparable to the well-known phosphorothioate modification. Additionally, this
      modification conferred extremely strong resistance to serum and 3'/5'
      exonucleases. In view of these results, we applied this modification to the
      knockdown of a therapeutically relevant human gene such as apolipoprotein B
      (ApoB). Further studies on the activation of the innate immune system showed that
      L-threoninol-modified RNAs are slightly less stimulatory than unmodified RNAs. 

PMID- 25375333
TI  - Spectrum-effect relationships as a systematic approach to traditional chinese
      medicine research: current status and future perspectives.
AB  - Component fingerprints are a recognized method used worldwide to evaluate the
      quality of traditional Chinese medicines (TCMs). To foster the strengths and
      circumvent the weaknesses of the fingerprint technique in TCM, spectrum-effect
      relationships would complementarily clarify the nature of pharmacodynamic effects
      in the practice of TCM. The application of the spectrum-effect relationship
      method is crucial for understanding and interpreting TCM development, especially
      in the view of the trends towards TCM modernization and standardization. The
      basic requirement for using this method is in-depth knowledge of the active
      material basis and mechanisms of action. It is a novel and effective approach to
      study TCMs and great progress has been made, but to make it more accurate for TCM
      research purposes, more efforts are needed. In this review, the authors summarize
      the current knowledge about the spectrum-effect relationship method, including
      the fingerprint methods, pharmacodynamics studies and the methods of establishing
      relationships between the fingerprints and pharmacodynamics. Some speculation
      regarding future perspectives for spectrum-effect relationship approaches in TCM
      modernization and standardization are also proposed. 

PMID- 25375334
TI  - Antifungal activity and computational study of constituents from Piper
      divaricatum essential oil against Fusarium infection in black pepper.
AB  - Fusarium disease causes considerable losses in the cultivation of Piper nigrum,
      the black pepper used in the culinary world. Brazil was the largest producer of
      black pepper, but in recent years has lost this hegemony, with a significant
      reduction in its production, due to the ravages produced by the Fusarium solani
      f. sp. piperis, the fungus which causes this disease. Scientific research seeks
      new alternatives for the control and the existence of other Piper species in the
      Brazilian Amazon, resistant to disease, are being considered in this context. The
      main constituents of the oil of Piper divaricatum are methyleugenol (75.0%) and
      eugenol (10.0%). The oil and these two main constituents were tested individually
      at concentrations of 0.25 to 2.5 mg/mL against F. solani f. sp. piperis,
      exhibiting strong antifungal index, from 18.0% to 100.0%. The 3D structure of the
      beta-glucosidase from Fusarium solani f. sp. piperis, obtained by homology
      modeling, was used for molecular docking and molecular electrostatic potential
      calculations in order to determine the binding energy of the natural substrates
      glucose, methyleugenol and eugenol. The results showed that beta-glucosidase
      (Asp45, Arg113, Lys146, Tyr193, Asp225, Trp226 and Leu99) residues play an
      important role in the interactions that occur between the protein-substrate and
      the engenol and methyleugenol inhibitors, justifying the antifungal action of
      these two phenylpropenes against Fusarium solani f. sp. piperis. 

PMID- 25375335
TI  - Efficiency of vanilla, patchouli and ylang ylang essential oils stabilized by
      iron oxide@C14 nanostructures against bacterial adherence and biofilms formed by
      Staphylococcus aureus and Klebsiella pneumoniae clinical strains.
AB  - Biofilms formed by bacterial cells are associated with drastically enhanced
      resistance against most antimicrobial agents, contributing to the persistence and
      chronicization of the microbial infections and to therapy failure. The purpose of
      this study was to combine the unique properties of magnetic nanoparticles with
      the antimicrobial activity of three essential oils to obtain novel nanobiosystems
      that could be used as coatings for catheter pieces with an improved resistance to
      Staphylococcus aureus and Klebsiella pneumoniae clinical strains adherence and
      biofilm development. The essential oils of ylang ylang, patchouli and vanilla
      were stabilized by the interaction with iron oxide@C14 nanoparticles to be
      further used as coating agents for medical surfaces. Iron oxide@C14 was prepared
      by co-precipitation of Fe+2 and Fe+3 and myristic acid (C14) in basic medium.
      Vanilla essential oil loaded nanoparticles pelliculised on the catheter samples
      surface strongly inhibited both the initial adherence of S. aureus cells
      (quantified at 24 h) and the development of the mature biofilm quantified at 48
      h. Patchouli and ylang-ylang essential oils inhibited mostly the initial
      adherence phase of S. aureus biofilm development. In the case of K. pneumoniae,
      all tested nanosystems exhibited similar efficiency, being active mostly against
      the adherence K. pneumoniae cells to the tested catheter specimens. The new
      nanobiosystems based on vanilla, patchouli and ylang-ylang essential oils could
      be of a great interest for the biomedical field, opening new directions for the
      design of film-coated surfaces with anti-adherence and anti-biofilm properties. 

PMID- 25375336
TI  - A novel method HPLC-DAD analysis of the Contentsof Moutan Cortexand Paeoniae
      Radix Alba with similar constituents-monoterpene glycosides in Guizhi Fuling Wan.
AB  - A variety of traditional Chinese medical formulations contain two or more herbs
      from the same genus or family. Although these herbs may have a similar appearance
      and constituents, they usually have different pharmacodynamic actions. A series
      of qualitative and quantitative analysis methods are developed to determine one
      or more compounds for quality control of medicine. As far as we know, no method
      has been found to determine the real ratio of the two herbs along with the
      prescription. In this study, we used HPLC-DAD as a way to determine the content
      of Moutan cortex (M) and Paeoniae radix alba (P) in GuizhiFuling Wan (GZFLW). An
      effective, accurate and reliable HPLC-DAD method was developed for detecting the
      content of M and P in GZFLW through the analysis of four monoterpeneglycosides,
      namely, galloylpaeoniflorin (1), paeoniflorin (2), mudanpioside C (3) and
      benzoylpaeoniflorin (4). Due to the different UV characteristics of the
      compounds, the detection wavelength was 270 nm for 1 and 2, while 3 and 4 were
      monitored at 254 nm and 230 nm, respectively. Four equations were put forward to
      describe the relationship between content of M as well as P and the four
      monoterpene glycosides in GZFLW. After validation, all the accuracies of the M
      and P contents in GZFLW were within 10%. The result showed that the method could
      be successfully applied to analyze the contents of M and P in GZFLW. Moreover,
      our method may be more widely used to control the quality of proprietary Chinese
      medicines, especially for those containing the same genus or family herbs, in
      industrial GMP production. 

PMID- 25375338
TI  - What is the future of heated transdermal delivery systems?

PMID- 25375337
TI  - Rational design and synthesis of altered peptide ligands based on human myelin
      oligodendrocyte glycoprotein 35-55 epitope: inhibition of chronic experimental
      autoimmune encephalomyelitis in mice.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the
      central nervous system and is an animal model of multiple sclerosis (MS).
      Although the etiology of MS remains unclear, there is evidence T-cell recognition
      of immunodominant epitopes of myelin proteins, such as the 35-55 epitope of
      myelin oligodendrocyte glycoprotein (MOG), plays a pathogenic role in the
      induction of chronic EAE. Cyclization of peptides is of great interest since the
      limited stability of linear peptides restricts their potential use as therapeutic
      agents. Herein, we have designed and synthesized a number of linear and cyclic
      peptides by mutating crucial T cell receptor (TCR) contact residues of the human
      MOG35-55 epitope. In particular, we have designed and synthesized cyclic altered
      peptide ligands (APLs) by mutating Arg41 with Ala or Arg41 and Arg46 with Ala.
      The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin
      (CLTR-Cl) using the Fmoc/t-Bu methodology. The purity of final products was
      verified by RP-HPLC and their identification was achieved by ESI-MS. It was found
      that the substitutions of Arg at positions 41 and 46 with Ala results in peptide
      analogues that reduce the severity of MOG-induced EAE clinical symptoms in
      C57BL/6 mice when co-administered with mouse MOG35-55 peptide at the time of
      immunization. 

PMID- 25375339
TI  - Buccal drug delivery: what's new and what does the future hold?

PMID- 25375341
TI  - Chimeric adeno-associated virus and bacteriophage: a potential targeted gene
      therapy vector for malignant glioma.
AB  - The incipient development of gene therapy for cancer has fuelled its progression
      from bench to bedside in mere decades. Of all malignancies that exist, gliomas
      are the largest class of brain tumors, and are renowned for their aggressiveness
      and resistance to therapy. In order for gene therapy to achieve clinical success,
      a multitude of barriers ranging from glioma tumor physiology to vector biology
      must be overcome. Many viral gene delivery systems have been subjected to
      clinical investigation; however, with highly limited success. In this review, the
      current progress and challenges of gene therapy for malignant glioma are
      discussed. Moreover, we highlight the hybrid adeno-associated virus and
      bacteriophage vector as a potential candidate for targeted gene delivery to brain
      tumors. 

PMID- 25375342
TI  - Delivery and targeting of nanoparticles into hair follicles.
AB  - It has been demonstrated that nanoparticles used for follicular delivery provide
      some advantages over conventional pathways, including improved skin
      bioavailability, enhanced penetration depth, prolonged residence duration, fast
      transport into the skin and tissue targeting. This review describes recent
      developments using nanotechnology approaches for drug delivery into the
      follicles. Different types of nanosystems may be employed for management of
      follicular permeation, such as polymeric nanoparticles, metallic nanocrystals,
      liposomes, and lipid nanoparticles. This review systematically introduces the
      mechanisms of follicles for nanoparticulate penetration, highlighting the
      therapeutic potential of drug-loaded nanoparticles for treating skin diseases.
      Special attention is paid to the use of nanoparticles in treating appendage
      related disorders, in particular, nanomedical strategies for treating alopecia,
      acne, and transcutaneous immunization. 

PMID- 25375343
TI  - Receptor-targeted drug delivery: current perspective and challenges.
AB  - Receptor-targeted drug delivery has been extensively explored for active
      targeting. However, the scarce clinical applications of such delivery systems
      highlight the implicit hurdles in development of such systems. These hurdles
      begin with lack of knowledge of differential expression of receptors, their
      accessibility and identification of newer receptors. Similarly, ligand-specific
      challenges range from proper choice of ligand and conjugation chemistry, to
      release of drug/delivery system from ligand. Finally, nanocarrier systems, which
      offer improved loading, biocompatibility and reduced premature degradation, also
      face multiple challenges. This review focuses on understanding these challenges,
      and means to overcome such challenges to develop efficient, targeted drug
      delivery systems. 

PMID- 25375344
TI  - Sequence-defined shuttles for targeted nucleic acid and protein delivery.
AB  - Molecular medicine opens into a space of novel specific therapeutic agents:
      intracellularly active drugs such as peptides, proteins or nucleic acids, which
      are not able to cross cell membranes and enter the intracellular space on their
      own. Through the development of cell-targeted shuttles for specific delivery,
      this restriction in delivery has the potential to be converted into an advantage.
      On the one hand, due to the multiple extra- and intracellular barriers, such
      carrier systems need to be multifunctional. On the other hand, they must be
      precise and reproducibly manufactured due to pharmaceutical reasons. Here we
      review the design of precise sequence-defined delivery carriers, including solid
      phase synthesized peptides and nonpeptidic oligomers, or nucleotide-based
      carriers such as aptamers and origami nanoboxes. 

PMID- 25375345
TI  - On the constitutive model of nitrogen-containing austenitic stainless steel 316LN
      at elevated temperature.
AB  - The nitrogen-containing austenitic stainless steel 316LN has been chosen as the
      material for nuclear main-pipe, which is one of the key parts in 3rd generation
      nuclear power plants. In this research, a constitutive model of nitrogen
      containing austenitic stainless steel is developed. The true stress-true strain
      curves obtained from isothermal hot compression tests over a wide range of
      temperatures (900-1250 degrees C) and strain rates (10(-3)-10 s(-1)), were
      employed to study the dynamic deformational behavior of and recrystallization in
      316LN steels. The constitutive model is developed through multiple linear
      regressions performed on the experimental data and based on an Arrhenius-type
      equation and Zener-Hollomon theory. The influence of strain was incorporated in
      the developed constitutive equation by considering the effect of strain on the
      various material constants. The reliability and accuracy of the model is verified
      through the comparison of predicted flow stress curves and experimental curves.
      Possible reasons for deviation are also discussed based on the characteristics of
      modeling process.

PMID- 25375347
TI  - Heparin-mimicking multilayer coating on polymeric membrane via LbL assembly of
      cyclodextrin-based supramolecules.
AB  - In this study, multifunctional and heparin-mimicking star-shaped supramolecules
      deposited 3D porous multilayer films with improved biocompatibility were
      fabricated via a layer-by-layer (LbL) self-assembly method on polymeric membrane
      substrates. Star-shaped heparin-mimicking polyanions (including
      poly(styrenesulfonate-co-sodium acrylate; Star-PSS-AANa) and
      poly(styrenesulfonate-co-poly(ethylene glycol)methyl ether methacrylate; Star-PSS
      EGMA)) and polycations (poly(methyl chloride-quaternized 2-(dimethylamino)ethyl
      methacrylate; Star-PMeDMA) were first synthesized by atom transfer radical
      polymerization (ATRP) from beta-cyclodextrin (beta-CD) based cores. Then assembly
      of 3D porous multilayers onto polymeric membrane surfaces was carried out by
      alternating deposition of the polyanions and polycations via electrostatic
      interaction. The surface morphology and composition, water contact angle, blood
      activation, and thrombotic potential as well as cell viability for the coated
      heparin-mimicking films were systematically investigated. The results of surface
      ATR-FTIR spectra and XPS spectra verified successful deposition of the star
      shaped supramolecules onto the biomedical membrane surfaces; scanning electron
      microscopy (SEM) and atomic force microscopy (AFM) observations revealed that the
      modified substrate had 3D porous surface morphology, which might have a great
      biological influence on the biointerface. Furthermore, systematic in vitro
      investigation of protein adsorption, platelet adhesion, human platelet factor 4
      (PF4, indicates platelet activation), activate partial thromboplastin time
      (APTT), thrombin time (TT), coagulation activation (thrombin-antithrombin III
      complex (TAT, indicates blood coagulant)), and blood-related complement
      activation (C3a and C5a, indicates inflammation potential) confirmed that the
      heparin-mimicking multilayer coated membranes exhibited ultralow blood component
      activations and excellent hemocompatibility. Meanwhile, after surface coating,
      endothelial cell viability was also promoted, which indicated that the heparin
      mimicking multilayer coating might extend the application fields of polymeric
      membranes in biomedical fields. 

PMID- 25375349
TI  - Dynamic fluorescence lifetime imaging based on acousto-optic deflectors.
AB  - We report a dynamic fluorescence lifetime imaging (D-FLIM) system that is based
      on a pair of acousto-optic deflectors for the random regions of interest (ROI)
      study in the sample. The two-dimensional acousto-optic deflector devices are used
      to rapidly scan the femtosecond excitation laser beam across the sample,
      providing specific random access to the ROI. Our experimental results using
      standard fluorescent dyes in live cancer cells demonstrate that the D-FLIM system
      can dynamically monitor the changing process of the microenvironment in the ROI
      in live biological samples.

PMID- 25375348
TI  - Comparative study of methods to calibrate the stiffness of a single-beam gradient
      force optical tweezers over various laser trapping powers.
AB  - Optical tweezers have become an important instrument in force measurements
      associated with various physical, biological, and biophysical phenomena.
      Quantitative use of optical tweezers relies on accurate calibration of the
      stiffness of the optical trap. Using the same optical tweezers platform operating
      at 1064 nm and beads with two different diameters, we present a comparative study
      of viscous drag force, equipartition theorem, Boltzmann statistics, and power
      spectral density (PSD) as methods in calibrating the stiffness of a single beam
      gradient force optical trap at trapping laser powers in the range of 0.05 to 1.38
      W at the focal plane. The equipartition theorem and Boltzmann statistic methods
      demonstrate a linear stiffness with trapping laser powers up to 355 mW, when used
      in conjunction with video position sensing means. The PSD of a trapped particle's
      Brownian motion or measurements of the particle displacement against known
      viscous drag forces can be reliably used for stiffness calibration of an optical
      trap over a greater range of trapping laser powers. Viscous drag stiffness
      calibration method produces results relevant to applications where trapped
      particle undergoes large displacements, and at a given position sensing
      resolution, can be used for stiffness calibration at higher trapping laser powers
      than the PSD method.

PMID- 25375350
TI  - Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using
      multimodal spectral diagnosis.
AB  - The goal of this study was to determine the diagnostic capability of a multimodal
      spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and
      nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman
      spectra from 137 lesions in 76 patients using custom-built optical fiber-based
      clinical systems. Biopsies of lesions were classified using standard
      histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL),
      basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma
      (SCC). Spectral data were analyzed using principal component analysis. Using
      multiple diagnostically relevant principal components, we built leave-one-out
      logistic regression classifiers. Classification results were compared with
      histopathology of the lesion. Sensitivity/specificity for classifying MM versus
      PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14
      lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71
      lesions) was 90%/85%. The best classification for nonmelanoma skin cancers
      required multiple modalities; however, the best melanoma classification occurred
      with Raman spectroscopy alone. The high diagnostic accuracy for classifying both
      melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as
      a clinical diagnostic device.

PMID- 25375351
TI  - Self-assembled Peptide nanofibers designed as biological enzymes for catalyzing
      ester hydrolysis.
AB  - The structural arrangement of amino acid residues in a native enzyme provides a
      blueprint for the design of artificial enzymes. One challenge of mimicking the
      catalytic center of a native enzyme is how to arrange the essential amino acid
      residues in an appropriate position. In this study, we designed an artificial
      hydrolase via self-assembly of short peptides to catalyze ester hydrolysis. When
      the assembled hydrolase catalytic sites were embedded in a matrix of peptide
      nanofibers, they exhibited much higher catalytic efficiency than the peptide
      nanofibers without the catalytic sites, suggesting that this well-ordered
      nanostructure is an attractive scaffold for developing new artificial enzymes.
      Furthermore, the cytotoxicity of the assembled hydrolase was evaluated with human
      cells, and the novel artificial biological enzyme showed excellent
      biocompatibility. 

PMID- 25375352
TI  - Genome-wide classification and evolutionary and expression analyses of citrus MYB
      transcription factor families in sweet orange.
AB  - MYB family genes are widely distributed in plants and comprise one of the largest
      transcription factors involved in various developmental processes and defense
      responses of plants. To date, few MYB genes and little expression profiling have
      been reported for citrus. Here, we describe and classify 177 members of the sweet
      orange MYB gene (CsMYB) family in terms of their genomic gene structures and
      similarity to their putative Arabidopsis orthologs. According to these analyses,
      these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R
      MYB). Gene structure analysis revealed that 1R-MYB genes possess relatively more
      introns as compared with 2R-MYB genes. Investigation of their chromosomal
      localizations revealed that these CsMYBs are distributed across nine chromosomes.
      Sweet orange includes a relatively small number of MYB genes compared with the
      198 members in Arabidopsis, presumably due to a paralog reduction related to
      repetitive sequence insertion into promoter and non-coding transcribed region of
      the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had
      fewer gene duplication events. Expression analysis revealed that the MYB gene
      family has a wide expression profile in sweet orange development and plays
      important roles in development and stress responses. In addition, 337 new
      putative microsatellites with flanking sequences sufficient for primer design
      were also identified from the 177 CsMYBs. These results provide a useful
      reference for the selection of candidate MYB genes for cloning and further
      functional analysis forcitrus. 

PMID- 25375353
TI  - Biomineralization-inspired synthesis of functional organic/inorganic hybrid
      materials: organic molecular control of self-organization of hybrids.
AB  - Organisms produce various organic/inorganic hybrid materials, which are called
      biominerals. They form through the self-organization of organic molecules and
      inorganic elements under ambient conditions. Biominerals often have highly
      organized and hierarchical structures from nanometer to macroscopic length
      scales, resulting in their remarkable physical and chemical properties that
      cannot be obtained by simple accumulation of their organic and inorganic
      constituents. These observations motivate us to create novel functional materials
      exhibiting properties superior to conventional materials--both synthetic and
      natural. Herein, we introduce recent progress in understanding biomineralization
      processes at the molecular level and the development of organic/inorganic hybrid
      materials by these processes. We specifically outline fundamental molecular
      studies on silica, iron oxide, and calcium carbonate biomineralization and
      describe material synthesis based on these mechanisms. These approaches allow us
      to design a variety of advanced hybrid materials with desired morphologies,
      sizes, compositions, and structures through environmentally friendly synthetic
      routes using functions of organic molecules.

PMID- 25375354
TI  - The progress of inflammation and oxidative stress in patients with chronic kidney
      disease.
AB  - BACKGROUND: The variations and their correlation of inflammation and oxidative
      stress in chronic kidney disease (CKD) have not been thoroughly understood.
      MATERIALS AND METHODS: Biomarkers of inflammation and oxidative stress were
      measured in a cohort of 176 patients with CKD ranging from stage 1 to 5 and 67
      healthy controls. Correlation analysis in levels between inflammation and
      oxidative stress was also performed with estimated glomerular filtration rate
      (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula.
      Concentrations of serum creatinine (Scr), hs-CRP (hypersensitive C reactive
      protein) and MDA (malondialdehyde) of these participants were measured again
      after 12 month follow-up. RESULTS: In the present study, with the development of
      CKD, serum levels of hs-CRP, interleukin-6 (IL-6) and MDA were significantly
      increased, and the serum levels of SOD (superoxide dismutase) and GSH-PX
      (glutathione peroxidase) were significantly decreased in these participants. eGFR
      was inversely associated with MDA and positively with SOD and GSH-PX when
      adjusting for age and hypertension therapy. IL-6 and hs-CRP were positively
      correlated with MDA, and negatively associated with SOD and GSH-PX. Notably,
      after 12-month follow-up, the increase in Scr was positively associated with the
      increase in hs-CRP (p < 0.01) and MDA (p < 0.05), respectively. CONCLUSIONS:
      Inflammation and oxidative stress interacted with each other and played pivotal
      roles in the development of CKD. Variation in eGFR was parallel with the changes
      of oxidative stress and inflammation when CKD developing.

PMID- 25375355
TI  - C1 domains: structure and ligand-binding properties.

PMID- 25375356
TI  - A high-density genetic map identifies a novel major QTL for boron efficiency in
      oilseed rape (Brassica napus L.).
AB  - Low boron (B) seriously limits the growth of oilseed rape (Brassica napus L.), a
      high B demand species that is sensitive to low B conditions. Significant
      genotypic variations in response to B deficiency have been observed among B.
      napus cultivars. To reveal the genetic basis for B efficiency in B. napus,
      quantitative trait loci (QTLs) for the plant growth traits, B uptake traits and
      the B efficiency coefficient (BEC) were analyzed using a doubled haploid (DH)
      population derived from a cross between a B-efficient parent, Qingyou 10, and a B
      inefficient parent, Westar 10. A high-density genetic map was constructed based
      on single nucleotide polymorphisms (SNPs) assayed using Brassica 60 K Infinium
      BeadChip Array, simple sequence repeats (SSRs) and amplified fragment length
      polymorphisms (AFLPs). The linkage map covered a total length of 2139.5 cM, with
      19 linkage groups (LGs) and an average distance of 1.6 cM between adjacent
      markers. Based on hydroponic evaluation of six B efficiency traits measured in
      three separate repeated trials, a total of 52 QTLs were identified, accounting
      for 6.14-46.27% of the phenotypic variation. A major QTL for BEC, qBEC-A3a, was
      co-located on A3 with other QTLs for plant growth and B uptake traits under low B
      stress. Using a subset of substitution lines, qBEC-A3a was validated and narrowed
      down to the interval between CNU384 and BnGMS436. The results of this study
      provide a novel major locus located on A3 for B efficiency in B. napus that will
      be suitable for fine mapping and marker-assisted selection breeding for B
      efficiency in B. napus. 

PMID- 25375357
TI  - Multiple functional risk variants in a SMAD7 enhancer implicate a colorectal
      cancer risk haplotype.
AB  - Genome-wide association studies (GWAS) of colorectal cancer (CRC) have led to the
      identification of a number of common variants associated with modest risk.
      Several risk variants map within the vicinity of TGFbeta/BMP signaling pathway
      genes, including rs4939827 within an intron of SMAD7 at 18q21.1. A previous study
      implicated a novel SNP (novel 1 or rs58920878) as a functional variant within an
      enhancer element in SMAD7 intron 4. In this study, we show that four SNPs
      including novel 1 (rs6507874, rs6507875, rs8085824, and rs58920878) in linkage
      disequilibrium (LD) with the index SNP rs4939827 demonstrate allele-specific
      enhancer effects in a large, multi-component enhancer of SMAD7. All four SNPs
      demonstrate allele-specific protein binding to nuclear extracts of CRC cell
      lines. Furthermore, some of the risk-associated alleles correlate with increased
      expression of SMAD7 in normal colon tissues. Finally, we show that the enhancer
      is responsive to BMP4 stimulation. Taken together, we propose that the associated
      CRC risk at 18q21.1 is due to four functional variants that regulate SMAD7
      expression and potentially perturb a BMP negative feedback loop in TGFbeta/BMP
      signaling pathways. 

PMID- 25375358
TI  - Stage-specific binding profiles of cohesin in resting and activated B lymphocytes
      suggest a role for cohesin in immunoglobulin class switching and maturation.
AB  - The immunoglobulin heavy chain locus (Igh) features higher-order chromosomal
      interactions to facilitate stage-specific assembly of the Ig molecule. Cohesin, a
      ring-like protein complex required for sister chromatid cohesion, shapes
      chromosome architecture and chromatin interactions important for transcriptional
      regulation and often acts together with CTCF. Cohesin is likely involved in B
      cell activation and Ig class switch recombination. Hence, binding profiles of
      cohesin in resting mature murine splenic B lymphocytes and at two stages after
      cell activation were elucidated by chromatin immunoprecipitation and deep
      sequencing. Comparative genomic analysis revealed cohesin extensively changes its
      binding to transcriptional control elements after 48 h of stimulation with LPS/IL
      4. Cohesin was clearly underrepresented at switch regions regardless of their
      activation status, suggesting that switch regions need to be cohesin-poor.
      Specific binding changes of cohesin at B-cell specific gene loci Pax5 and Blimp-1
      indicate new cohesin-dependent regulatory pathways. Together with conserved
      cohesin/CTCF sites at the Igh 3'RR, a prominent cohesin/CTCF binding site was
      revealed near the 3' end of Calpha where PolII localizes to 3' enhancers. Our
      study shows that cohesin likely regulates B cell activation and maturation,
      including Ig class switching. 

PMID- 25375359
TI  - Methylation of DACT2 promotes papillary thyroid cancer metastasis by activating
      Wnt signaling.
AB  - Thyroid cancer is the most common endocrine malignant disease and the incidence
      is increasing. DACT2 was found frequently methylated in human lung cancer and
      hepatocellular carcinoma. To explore the epigenetic change and the role of DACT2
      in thyroid cancer, 7 thyroid cancer cell lines, 10 cases of non-cancerous thyroid
      tissue samples and 99 cases of primary thyroid cancer samples were involved in
      this study. DACT2 was expressed and unmethylated in K1, SW579, FTC-133, TT, W3
      and 8505C cell lines. Loss of expression and complete methylation was found in
      TPC-1 cells. Restoration of DACT2 expression was induced by 5-aza-2'deoxycytidine
      treatment. It demonstrates that the expression of DACT2 was regulated by promoter
      region methylation. In human primary papillary thyroid cancer, 64.6% (64/99) was
      methylated and methylation of DACT2 was related to lymph node metastasis
      (p<0.01). Re-expression of DACT2 suppresses cell proliferation, invasion and
      migration in TPC-1 cells. The activity of TCF/LEF was inhibited by DACT2 in wild
      type or mutant beta-catenin cells. The activity of TCF/LEF was increased by co
      transfecting DACT2 and Dvl2 in wild-type or mutant beta-catenin cells.
      Overexpression of wild-type beta-catenin promotes cell migration and invasion in
      DACT2 stably expressed cells. The expression of beta-catenin, c-myc, cyclinD1 and
      MMP-9 were decreased and the level of phosphorylated beta-catenin (p-beta
      catenin) was increased after restoration of DACT2 expression in TPC-1 cells. The
      expression of beta-catenin, c-myc, cyclinD1 and MMP-9 were increased and the
      level of p-beta-catenin was reduced after knockdown of DACT2 in W3 and SW579
      cells. These results suggest that DACT2 suppresses human papillary thyroid cancer
      growth and metastasis by inhibiting Wnt signaling. In conclusion, DACT2 is
      frequently methylated in papillary thyroid cancer. DACT2 expression was regulated
      by promoter region methylation. DACT2 suppresses papillary thyroid cancer
      proliferation and metastasis by inhibiting Wnt signaling.

PMID- 25375360
TI  - Iron status and reproduction in US women: National Health and Nutrition
      Examination Survey, 1999-2006.
AB  - Women experience significant changes in iron status throughout their reproductive
      lifespans. While this is evident in regions with high rates of malnutrition and
      infectious disease, the extent of reproductive-related changes is less well known
      in countries with low rates of iron deficiency anemia, such as the United States.
      The goal of this study is determine the relationship between women's reproductive
      variables (pregnancy, parity, currently breastfeeding, regular menstruation,
      hormonal contraceptive use, and age at menarche) and iron status (hemoglobin,
      ferritin, transferrin receptor, and % transferrin saturation) using an
      anthropological framework for interpreting the results. Data from women aged 18
      49 were taken from the 1999-2006 US NHANES, a nationally representative cross
      sectional sample of US women. Using multiple imputation and complex survey
      statistics, women's reproductive variables were regressed against indicators of
      iron status. Pregnant women had significantly poorer iron status, by most
      indicators, than non-pregnant women. All biomarkers demonstrated significantly
      lower iron levels with increasing parity. Women who were having regular periods
      had iron indicators that suggested decreased iron levels, while women who used
      hormonal contraceptives had iron indicators that suggested increased iron levels.
      Despite relatively good iron status and widespread availability of iron-rich
      foods in the US, women still exhibit patterns of iron depletion across several
      reproductive variables of interest. These results contribute to an ecological
      approach to iron status that seeks to understand variation in iron status, with
      the hopes that appropriate, population-specific recommendations can be developed
      to improve women's health. 

PMID- 25375361
TI  - Genomic evidence of rapid and stable adaptive oscillations over seasonal time
      scales in Drosophila.
AB  - In many species, genomic data have revealed pervasive adaptive evolution
      indicated by the fixation of beneficial alleles. However, when selection
      pressures are highly variable along a species' range or through time adaptive
      alleles may persist at intermediate frequencies for long periods. So called
      "balanced polymorphisms" have long been understood to be an important component
      of standing genetic variation, yet direct evidence of the strength of balancing
      selection and the stability and prevalence of balanced polymorphisms has remained
      elusive. We hypothesized that environmental fluctuations among seasons in a North
      American orchard would impose temporally variable selection on Drosophila
      melanogaster that would drive repeatable adaptive oscillations at balanced
      polymorphisms. We identified hundreds of polymorphisms whose frequency oscillates
      among seasons and argue that these loci are subject to strong, temporally
      variable selection. We show that these polymorphisms respond to acute and
      persistent changes in climate and are associated in predictable ways with
      seasonally variable phenotypes. In addition, our results suggest that adaptively
      oscillating polymorphisms are likely millions of years old, with some possibly
      predating the divergence between D. melanogaster and D. simulans. Taken together,
      our results are consistent with a model of balancing selection wherein rapid
      temporal fluctuations in climate over generational time promotes adaptive genetic
      diversity at loci underlying polygenic variation in fitness related phenotypes. 

PMID- 25375362
TI  - MiRNA expression may account for chronic but not for acute regulation of mRNA
      expression in human thyroid tumor models.
AB  - BACKGROUND: For thyroid tumorigenesis, two main human in vitro models are
      available: primary cultures of human thyrocytes treated with TSH or EGF/serum as
      models for autonomous adenomas (AA) or papillary thyroid carcinomas (PTC)
      respectively, and human thyroid tumor derived cell lines. Previous works of our
      group have assessed properties of those models, with a special emphasis on mRNA
      regulations. It is often assumed that miRNA may be one of the primary events
      inducing these mRNA regulations. METHODS: The purpose of this study was to
      investigate the representativity of those models to study microRNA regulations
      and their relation with mRNA expression. To achieve this aim, the miRNA
      expressions profiles of primary cultures treated with TSH or EGF/serum and of 6
      thyroid cancer cell lines were compared to the expression profiles of 35 tumor
      tissues obtained by microarrays. RESULTS: Our data on primary cultures have shown
      that the TSH or EGF/serum treatment did not greatly modify the microRNA
      expression profiles, which is contrary to what is observed for mRNA expression
      profiles, although they still evolved differently according to the treatment. The
      analysis of miRNA and mRNA expressions profiles in the cell lines has shown that
      they have evolved into a common, dedifferentiated phenotype, closer to ATC than
      to the tumors they are derived from. CONCLUSIONS: Long-terms TSH or EGF/serum
      treatments do not mimic AA or PTC respectively in terms of miRNA expression as
      they do for mRNA, suggesting that the regulations of mRNA expression induced by
      these physiological agents occur independently of miRNA. The general patterns of
      miRNA expression in the cell lines suggest that they represent a useful model for
      undifferentiated thyroid cancer. Mirna probably do not mediate the rapid changes
      in gene expression in rapid cell biology regulation.

PMID- 25375364
TI  - Experimental characterization of breakage rate of colloidal aggregates in
      axisymmetric extensional flow.
AB  - Aggregates prepared under fully destabilized conditions by the action of Brownian
      motion were exposed to an extensional flow generated at the entrance of a sudden
      contraction. Two noninvasive techniques were used to monitor their breakup
      process [i.e. light scattering and three-dimensional (3D) particle tracking
      velocimetry (3D-PTV)]. While the first one can be used to measure the size and
      the morphology of formed fragments after the breakage event, the latter is
      capable of resolving trajectories of individual aggregates up to the breakage
      point as well as the trajectories of formed fragments. Furthermore, measured
      velocity gradients were used to determine the local hydrodynamic conditions at
      the breakage point. All this information was combined to experimentally determine
      for the first time the breakage rate of individual aggregates, given in the form
      of a size reduction rate K(R), as a function of the applied strain rate, as well
      as the properties of the formed fragments (i.e., the number of formed fragments
      and the size ratio between the largest fragment and the original aggregate). It
      was found that K(R) scales with the applied strain rate according to a power law
      with the slope being dependent on the initial fractal dimension only, while the
      obtained data indicates a linear dependency of K(R) with the initial aggregate
      size. Furthermore, the probability distribution function (PDF) of the number of
      formed fragments and the PDF of the size ratio between the largest fragment and
      the original aggregate indicate that breakage will result with high probability
      (75%) in the formation of two to three fragments with a rather asymmetric ratio
      of sizes of about 0.8. The obtained results are well in agreement with the
      results from the numerical simulations published in the literature.

PMID- 25375363
TI  - Establishing a multidisciplinary context for modeling 3D facial shape from DNA.

PMID- 25375365
TI  - Insights into the molecular flexibility of theta-defensins by NMR relaxation
      analysis.
AB  - theta-Defensins are mammalian cyclic peptides that have antimicrobial activity
      and show potential as stable scaffolds for peptide-based drug design. The cyclic
      cystine ladder structural motif of theta-defensins has been characterized using
      NMR spectroscopy and is important for their structure and stability. However, the
      effect of the pronounced elongated topology of theta-defensins on their molecular
      motion is not yet understood. Studies of molecular motion by NMR relaxation
      measurements have been facilitated by the recent development of a semirecombinant
      method for producing cyclic peptides that allows for isotopic labeling. Here we
      have undertaken a multifield (15)N NMR relaxation analysis of the anti-HIV theta
      defensin, HTD-2, and interpreted the experimental data using various models of
      overall and internal molecular motion. We found that it was necessary to apply a
      model that includes internal motion to account for the variations in the
      experimental T1 and NOE data at different backbone amide sites in the peptide.
      Although an isotropic model with internal motion was the simplest model that
      provided a satisfactory fit with the experimental data, we cannot exclude the
      possibility that overall motion is anisotropic, especially considering the
      strikingly elongated topology of theta-defensins. The presence of flexible side
      chains, self-association, interactions with solvent, and internal motions are all
      potential contributors to the observed relaxation data. Internal motion
      consistent with the constraints imposed by the cyclic cystine ladder was observed
      in that the order parameters, S(2), show that residues in the turns are more
      flexible than those in the beta-sheet. This study provides insights into the
      dynamics of theta-defensins and information that might be useful in their
      application as scaffolds in drug design. 

PMID- 25375366
TI  - Comparison of the effects of two legal blood alcohol limits: the presence of
      alcohol in traffic accidents according to category of driver in Izmir, Turkey.
AB  - OBJECTIVES: Under existing Turkish road traffic law, there are 2 different blood
      alcohol concentration (BAC) limits allowed for drivers in 2013: zero blood
      alcohol and <=0.50 g/L. All public transport, taxi, commercial, and official
      vehicle drivers must maintain a zero blood alcohol concentration while driving.
      Private vehicle drivers must maintain a BAC of 0.50 g/L or lower. The aim of the
      recent study was to evaluate the effect of these 2 legal blood alcohol limits on
      nonfatal traffic accidents that occurred due to the driver being under the
      influence of alcohol. METHODS: This retrospective study was performed to evaluate
      the blood alcohol concentration of 224 drivers in nonfatal road accidents between
      June 2010 and July 2011 using headspace gas chromatography at the Izmir Forensic
      Medicine Group Presidency, Turkey. All cases evaluated by the toxicology
      department were entered into a database. We used descriptive statistics, chi(2)
      test, and independent sampling test to analyze the data. RESULTS: The total
      number of drivers involved in nonfatal traffic accidents was 224; 191 were
      private vehicle drivers and 33 were public transport, taxi, commercial, and
      official vehicle drivers. In the present study, alcohol was detected in the blood
      of about 27.2% (n = 61) of the 224 drivers. Sixty (31.4%) private vehicle drivers
      involved in nonfatal traffic accidents tested positive for alcohol. BAC values
      were also above the legal limit (0.50 g/L) in 27.7% (n = 53) of private vehicle
      drivers. However, the BAC was above the legal limit in only 3% (n = 1) of public
      transport, commercial, and official vehicle drivers involved in nonfatal traffic
      accidents. These results showed that private vehicle drivers subject to a BAC
      limit of <=0.50 g/L were significantly associated with an increased risk of
      nonfatal accident involvement than drivers subject to a zero BAC limit (odds
      ratio [OR] = 12.29, 95% confidence interval [CI], 1.64-92.22; Fisher's exact
      test, P <.001). Mean BAC in private vehicle drivers subject to a 0.50 g/L level
      (52.60 mg/dl +/- 94.84) was significantly higher than that of drivers subject to
      a zero alcohol level (10.76 mg/dl +/- 61.80; t = 2.44, P <.001). CONCLUSION: In
      light of our results, lowering the BAC limit for private vehicle drivers may
      reduce the level of driving under the influence of alcohol. A change in the law
      will decrease the rates of alcohol-related road accidents in Turkey.

PMID- 25375367
TI  - Design and rationale of the Paliperidone Palmitate Research in Demonstrating
      Effectiveness (PRIDE) study: a novel comparative trial of once-monthly
      paliperidone palmitate versus daily oral antipsychotic treatment for delaying
      time to treatment failure in persons with schizophrenia.
AB  - BACKGROUND: Public health considerations require that clinical trials address the
      complex "real-world" needs of patients with chronic illnesses. This is
      particularly true for persons with schizophrenia, whose management is frequently
      complicated by factors such as comorbid substance abuse, homelessness, and
      contact with the criminal justice system. In addition, barriers to obtaining
      health care in the United States often prevent successful community reentry and
      optimal patient management. Further, nonadherence to treatment is common, and
      this reinforces cycles of relapse and recidivism. Long-acting injectable
      antipsychotic therapy may facilitate continuity of treatment and support better
      outcomes, particularly in patients who face these challenges. Clinical trials
      with classical explanatory designs may not be the best approaches for evaluating
      these considerations. We describe the design and rationale of a novel trial that
      combines both explanatory and pragmatic design features and studies persons with
      schizophrenia who face these challenges. DESIGN AND RATIONALE: The Paliperidone
      Palmitate Research in Demonstrating Effectiveness (PRIDE) study is a prospective,
      open-label, randomized, 15-month study conducted between May 5, 2010, and
      December 9, 2013, comparing long-acting injectable paliperidone palmitate and
      oral antipsychotic medications in subjects with schizophrenia (according to DSM
      IV criteria). Investigators and subjects had broad flexibility for treatment
      decision-making, thus making it a model that better reflects real-world practice.
      The primary end point was time to treatment failure, defined as
      arrest/incarceration psychiatric hospitalization; suicide; treatment
      discontinuation or supplementation due to inadequate efficacy, safety, or
      tolerability; or increased psychiatric services to prevent hospitalization. This
      end point was adjudicated by a blinded event monitoring board. Patients were
      followed to the 15-month end point, regardless of whether they were maintained on
      their initial randomized treatment. This article provides some of the reasoning
      behind the authors' choices when combining features from both explanatory and
      pragmatic approaches to this trial's design. CONCLUSIONS: The PRIDE study
      incorporates real-world design features in a novel, prospective, comparative
      study of long-acting injectable and oral antipsychotics in persons with
      schizophrenia who have had recent contact with the criminal justice system.
      Insights provided should help the reader to better understand the need for more
      real-world approaches for clinical studies and how a broader approach can better
      aid clinical treatment and public health decision-making. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01157351.

PMID- 25375368
TI  - Fundamental processes in semiconductor nanocrystals.

PMID- 25375369
TI  - Nursing workload in intensive care unit trauma patients: analysis of associated
      factors.
AB  - BACKGROUND: From the perspective of nurses, trauma patients in the Intensive Care
      Unit (ICU) demand a high degree of nursing workload due to hemodynamic
      instability and the severity of trauma injuries. This study aims to identify the
      factors related to the high nursing workload required for trauma victims admitted
      to the ICU. METHODS: This is a prospective, cross-sectional study using
      descriptive and correlation analyses, conducted with 200 trauma patients admitted
      to an ICU in the city of Sao Paulo, Brazil. The nursing workload was measured
      using the Nursing Activities Score (NAS). The distribution of the NAS values into
      tertiles led to the identification of two research groups: medium/low workload
      and high workload. The Chi-square, Fisher's exact, Mann-Whitney and multiple
      logistic regression tests were utilized for the analyses. FINDINGS: The majority
      of patients were male (82.0%) and suffered blunt trauma (94.5%), with traffic
      accidents (57.5%) and falls (31.0%) being prevalent. The mean age was 40.7 years
      (+/- 18.6) and the mean NAS was 71.3% (+/- 16.9). Patient gender, the presence of
      pulmonary failure, the number of injured body regions and the risk of death
      according to the Simplified Acute Physiology Score II were factors associated
      with a high degree of nursing workload in the first 24 hours following admission
      to the ICU. CONCLUSION: Workload demand was higher in male patients with
      physiological instability and multiple severe trauma injuries who developed
      pulmonary failure.

PMID- 25375370
TI  - 20(S)-protopanaxadiol inhibition of progression and growth of castration
      resistant prostate cancer.
AB  - Castration-resistant progression of prostate cancer after androgen deprivation
      therapies remains the most critical challenge in the clinical management of
      prostate cancer. Resurgent androgen receptor (AR) activity is an established
      driver of castration-resistant progression, and upregulation of the full-length
      AR (AR-FL) and constitutively-active AR splice variants (AR-Vs) has been
      implicated to contribute to the resurgent AR activity. We reported previously
      that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) can reduce the abundance of
      both AR-FL and AR-Vs. In the present study, we further showed that the effect of
      PPD on AR expression and target genes was independent of androgen. PPD treatment
      resulted in a suppression of ligand-independent AR transactivation. Moreover, PPD
      delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen
      deprivation and inhibited the growth of castration-resistant 22Rv1 xenograft
      tumors with endogenous expression of AR-FL and AR-Vs. This was accompanied by a
      decline in serum prostate-specific antigen levels as well as a decrease in AR
      levels and mitoses in the tumors. Notably, the 22Rv1 xenograft tumors were
      resistant to growth inhibition by the next-generation anti-androgen enzalutamide.
      The present study represents the first to show the preclinical efficacy of PPD in
      inhibiting castration-resistant progression and growth of prostate cancer. The
      findings provide a rationale for further developing PPD or its analogues for
      prostate cancer therapy. 

PMID- 25375371
TI  - Transplantation of ATP7B-transduced bone marrow mesenchymal stem cells decreases
      copper overload in rats.
AB  - BACKGROUND: Recent studies have demonstrated that transplantation of ATP7B
      transduced hepatocytes ameliorates disease progression in LEC (Long-Evans
      Cinnamon) rats, a model of Wilson's disease (WD). However, the inability of
      transplanted cells to proliferate in a normal liver hampers long-term treatment.
      In the current study, we investigated whether transplantation of ATP7B-transduced
      bone marrow mesenchymal stem cells (BM-MSCs) could decrease copper overload in
      LEC rats. MATERIALS AND METHODS: The livers of LEC rats were preconditioned with
      radiation (RT) and/or ischemia-reperfusion (IRP) before portal vein infusion of
      ATP7B-transduced MSCs (MSCsATP7B). The volumes of MSCsATP7B or saline injected as
      controls were identical. The expression of ATP7B was analyzed by real-time
      quantitative polymerase chain reaction (RT-PCR) at 4, 12 and 24 weeks post
      transplantation. MSCATP7B repopulation, liver copper concentrations, serum
      ceruloplasmin levels, and alanine transaminase (ALT) and aspartate transaminase
      (AST) levels were also analyzed at each time-point post-transplantation. RESULTS:
      IRP-plus-RT preconditioning was the most effective strategy for enhancing the
      engraftment and repopulation of transplanted MSCsATP7B. This strategy resulted in
      higher ATP7B expression and serum ceruloplasmin, and lower copper concentration
      in this doubly preconditioned group compared with the saline control group, the
      IRP group, and the RT group at all three time-points post-transplantation (p<0.05
      for all). Moreover, 24 weeks post-transplantation, the levels of ALT and AST in
      the IRP group, the RT group, and the IRP-plus-RT group were all significantly
      decreased compared to those of the saline group (p<0.05 compared with the IRP
      group and RT group, p<0.01 compared with IRP-plus-RT group); ALT and AST levels
      were significantly lower in the IRP-plus-RT group compared to either the IRP
      group or the RT group (p<0.01 and p<0.05. respectively). CONCLUSIONS: These
      results demonstrate that transplantation of MSCsATP7B into IRP-plus-RT
      preconditioned LEC rats decreased copper overload and was associated with an
      increase in MSC engraftment and repopulation.

PMID- 25375372
TI  - Tumor-induced senescent T cells promote the secretion of pro-inflammatory
      cytokines and angiogenic factors by human monocytes/macrophages through a
      mechanism that involves Tim-3 and CD40L.
AB  - Solid tumors are infiltrated by immune cells where macrophages and senescent T
      cells are highly represented. Within the tumor microenvironment, a cross-talk
      between the infiltrating cells may occur conditioning the characteristic of the
      in situ immune response. Our previous work showed that tumors induce senescence
      of T cells, which are powerful suppressors of lympho-proliferation. In this
      study, we report that Tumor-Induced Senescent (TIS)-T cells may also modulate
      monocyte activation. To gain insight into this interaction, CD4+ or CD8+TIS-T or
      control-T cells were co-incubated with autologous monocytes under inflammatory
      conditions. After co-culture with CD4+ or CD8+TIS-T cells, CD14+
      monocytes/macrophages (Mo/Ma) exhibit a higher expression of CD16+ cells and a
      reduced expression of CD206. These Mo/Ma produce nitric oxide and reactive oxygen
      species; however, TIS-T cells do not modify phagocyte capacity of Mo/Ma. TIS-T
      modulated-Mo/Ma show a higher production of pro-inflammatory cytokines (TNF, IL
      1beta and IL-6) and angiogenic factors (MMP-9, VEGF-A and IL-8) and a lower IL-10
      and IP-10 secretion than monocytes co-cultured with controls. The mediator(s)
      present in the supernatant of TIS-T cell/monocyte-macrophage co-cultures
      promote(s) tubulogenesis and tumor-cell survival. Monocyte-modulation induced by
      TIS-T cells requires cell-to-cell contact. Although CD4+ shows different behavior
      from CD8+TIS-T cells, blocking mAbs against T-cell immunoglobulin and mucin
      protein 3 and CD40 ligand reduce pro-inflammatory cytokines and angiogenic
      factors production, indicating that these molecules are involved in
      monocyte/macrophage modulation by TIS-T cells. Our results revealed a novel role
      for TIS-T cells in human monocyte/macrophage modulation, which may have
      deleterious consequences for tumor progression. This modulation should be
      considered to best tailor the immunotherapy against cancer. 

PMID- 25375373
TI  - CDK1 plays an important role in the maintenance of pluripotency and genomic
      stability in human pluripotent stem cells.
AB  - Human embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) are
      characterised by an unusual and tightly regulated cell cycle that has been shown
      to be important for the maintenance of a pluripotent phenotype. Cyclin-dependant
      kinase 1 (CDK1) is a key player in cell cycle regulation and particularly
      mitosis; however, its role has not been studied previously in hESC and hiPSC. To
      investigate the impacts of CDK1 downregulation, we performed RNA interference
      studies which in addition to expected mitotic deficiencies revealed a large range
      of additional phenotypes related to maintenance of pluripotency, ability to
      repair double strand breaks (DSBs) and commitment to apoptosis. Downregulation of
      CDK1 led to the loss of typical pluripotent stem cell morphology, downregulation
      of pluripotency markers and upregulation of a large number of differentiation
      markers. In addition, human pluripotent stem cells with reduced CDK1 expression
      accumulated a higher number of DSBs were unable to activate CHK2 expression and
      could not maintain G2/M arrest upon exposure to ionising radiation. CDK1
      downregulation led to the accumulation of cells with abnormal numbers of mitotic
      organelles, multiple chromosomal abnormalities and polyploidy. Furthermore, such
      cells demonstrated an inability to execute apoptosis under normal culture
      conditions, despite a significant increase in the expression of active PARP1,
      resulting in tolerance and very likely further propagation of genomic
      instabilities and ensuing of differentiation process. On the contrary, apoptosis
      but not differentiation, was the preferred route for such cells when they were
      subjected to ionising radiation. Together these data suggest that CDK1 regulates
      multiple events in human pluripotent stem cells ranging from regulation of
      mitosis, G2/M checkpoint maintenance, execution of apoptosis, maintenance of
      pluripotency and genomic stability. 

PMID- 25375374
TI  - Regulation of autophagy by polyphenolic compounds as a potential therapeutic
      strategy for cancer.
AB  - Autophagy, a lysosomal degradation pathway for cellular constituents and
      organelles, is an adaptive and essential process required for cellular
      homeostasis. Although autophagy functions as a survival mechanism in response to
      cellular stressors such as nutrient or growth factor deprivation, it can also
      lead to a non-apoptotic form of programmed cell death (PCD) called autophagy
      induced cell death or autophagy-associated cell death (type II PCD). Current
      evidence suggests that cell death through autophagy can be induced as an
      alternative to apoptosis (type I PCD), with therapeutic purpose in cancer cells
      that are resistant to apoptosis. Thus, modulating autophagy is of great interest
      in cancer research and therapy. Natural polyphenolic compounds that are present
      in our diet, such as rottlerin, genistein, quercetin, curcumin, and resveratrol,
      can trigger type II PCD via various mechanisms through the canonical (Beclin-1
      dependent) and non-canonical (Beclin-1 independent) routes of autophagy. The
      capacity of these compounds to provide a means of cancer cell death that enhances
      the effects of standard therapies should be taken into consideration for
      designing novel therapeutic strategies. This review focuses on the autophagy- and
      cell death-inducing effects of these polyphenolic compounds in cancer. 

PMID- 25375375
TI  - Bortezomib enhances cancer cell death by blocking the autophagic flux through
      stimulating ERK phosphorylation.
AB  - The antitumor activity of an inhibitor of 26S proteasome bortezomib (Velcade) has
      been observed in various malignancies, including colon cancer, prostate cancer,
      breast cancer, and ovarian cancer. Bortezomib has been proposed to stimulate
      autophagy, but scientific observations did not always support this. Interactions
      between ERK activity and autophagy are complex and not completely clear.
      Autophagy proteins have recently been shown to regulate the functions of ERK, and
      ERK activation has been found to induce autophagy. On the other hand, sustained
      activation of ERK has also been shown to inhibit the maturation step of the
      autophagy process. In this study, we sought to identify the mechanism of
      autophagy regulation in cancer cells treated with bortezomib. Our results
      indicate that bortezomib blocked the autophagic flux without inhibiting the
      fusion of the autophagosome and lysosome. In ovarian cancer, as well as
      endometrial cancer and hepatocellular carcinoma cells, bortezomib inhibited
      protein degradation in lysosomes by suppressing cathepsins, which requires the
      participation of ERK phosphorylation, but not JNK or p38. Our findings that ERK
      phosphorylation reduced cathepsins further explain how ERK phosphorylation
      inhibits the autophagic flux. In conclusion, bortezomib may induce ERK
      phosphorylation to suppress cathepsin B and inhibit the catalytic process of
      autophagy in ovarian cancer and other solid tumors. The inhibition of cisplatin
      induced autophagy by bortezomib can enhance chemotherapy efficacy in ovarian
      cancer. As we also found that bortezomib blocks the autophagic flux in other
      cancers, the synergistic cytotoxic effect of bortezomib by abolishing
      chemotherapy-related autophagy may help us develop strategies of combination
      therapies for multiple cancers. 

PMID- 25375376
TI  - A sustained deficiency of mitochondrial respiratory complex III induces an
      apoptotic cell death through the p53-mediated inhibition of pro-survival
      activities of the activating transcription factor 4.
AB  - Generation of energy in mitochondria is subjected to physiological regulation at
      many levels, and its malfunction may result in mitochondrial diseases.
      Mitochondrial dysfunction is associated with different environmental influences
      or certain genetic conditions, and can be artificially induced by inhibitors
      acting at different steps of the mitochondrial electron transport chain (ETC). We
      found that a short-term (5 h) inhibition of ETC complex III with myxothiazol
      results in the phosphorylation of translation initiation factor eIF2alpha and
      upregulation of mRNA for the activating transcription factor 4 (ATF4) and several
      ATF4-regulated genes. The changes are characteristic for the adaptive integrated
      stress response (ISR), which is known to be triggered by unfolded proteins,
      nutrient and metabolic deficiency, and mitochondrial dysfunctions. However, after
      a prolonged incubation with myxothiazol (13-17 h), levels of ATF4 mRNA and ATF4
      regulated transcripts were found substantially suppressed. The suppression was
      dependent on the p53 response, which is triggered by the impairment of the
      complex III-dependent de novo biosynthesis of pyrimidines by mitochondrial
      dihydroorotate dehydrogenase. The initial adaptive induction of ATF4/ISR acted to
      promote viability of cells by attenuating apoptosis. In contrast, the induction
      of p53 upon a sustained inhibition of ETC complex III produced a pro-apoptotic
      effect, which was additionally stimulated by the p53-mediated abrogation of the
      pro-survival activities of the ISR. Interestingly, a sustained inhibition of ETC
      complex I by piericidine did not induce the p53 response and stably maintained
      the pro-survival activation of ATF4/ISR. We conclude that a downregulation of
      mitochondrial ETC generally induces adaptive pro-survival responses, which are
      specifically abrogated by the suicidal p53 response triggered by the genetic
      risks of the pyrimidine nucleotide deficiency. 

PMID- 25375377
TI  - IFN-gamma induces aberrant CD49b+ NK cell recruitment through regulating CX3CL1:
      a novel mechanism by which IFN-gamma provokes pregnancy failure.
AB  - Interferon-gamma (IFN-gamma), a pleiotropic lymphokine, has important regulatory
      effects on many cell types. Although IFN-gamma is essential for the initiation of
      uterine vascular modifications and maintenance of decidual integrity, IFN-gamma
      administration can also cause pregnancy failure in many species. However, little
      is known about the effector mechanisms involved. In this study, using an IFN
      gamma-induced abortion mouse model, we reported that no Dolichos biflorus
      agglutinin lectin-positive uterine natural killer (uNK) cells were observed in
      the uteri from IFN-gamma-induced abortion mice. By contrast, the percentage of
      CD3(-)CD49b(+) NK cells in the uterus and blood from a foetal resorption group
      was significantly higher than that of the control group. Similarly, significantly
      upregulated expression of CD49b (a pan-NK cell marker), CX3CL1 and CX3CR1 (CX3CL1
      receptor) was detected in the uteri of IFN-gamma-induced abortion mice. Using
      isolated uterine stromal cells, we showed that upregulated expression of CX3CL1
      by IFN-gamma was dependent on a Janus family kinase 2-signal transducers and
      activators of transcription 1 (JAK2-STAT1) pathway. We further demonstrated the
      chemotactic activity of CX3CL1 in uterine stromal cell conditioned medium on
      primary splenic NK cells. Finally, we observed increased recruitment of CD49b(+)
      NK cells into the endometrium after exogenous CX3CL1 administration.
      Collectively, our findings indicate that IFN-gamma can significantly increase
      uterine CX3CL1 expression via activation of the JAK2-STAT1 pathway, thus inducing
      CD49b(+) NK cell uterine homing, and eventually provoke foetal loss. Thus, we
      provide a new line of evidence correlating the deleterious effects of IFN-gamma
      on pregnancy with the aberrant regulation of CX3CL1 and CD49b(+) NK cells.

PMID- 25375378
TI  - Cancer cell death induced by novel small molecules degrading the TACC3 protein
      via the ubiquitin-proteasome pathway.
AB  - The selective degradation of target proteins with small molecules is a novel
      approach to the treatment of various diseases, including cancer. We have
      developed a protein knockdown system with a series of hybrid small compounds that
      induce the selective degradation of target proteins via the ubiquitin-proteasome
      pathway. In this study, we designed and synthesized novel small molecules called
      SNIPER(TACC3)s, which target the spindle regulatory protein transforming acidic
      coiled-coil-3 (TACC3). SNIPER(TACC3)s induce poly-ubiquitylation and proteasomal
      degradation of TACC3 and reduce the TACC3 protein level in cells. Mechanistic
      analysis indicated that the ubiquitin ligase APC/C(CDH1) mediates the
      SNIPER(TACC3)-induced degradation of TACC3. Intriguingly, SNIPER(TACC3)
      selectively induced cell death in cancer cells expressing a larger amount of
      TACC3 protein than normal cells. These results suggest that protein knockdown of
      TACC3 by SNIPER(TACC3) is a potential strategy for treating cancers
      overexpressing the TACC3 protein. 

PMID- 25375382
TI  - Reflections on the use of restraint and seclusion: a 10-year update.

PMID- 25375379
TI  - Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki
      cells through downregulation of Mcl-1 expression and upregulation of Bim
      expression.
AB  - Although ABT-737, a small-molecule Bcl-2/Bcl-xL inhibitor, has recently emerged
      as a novel cancer therapeutic agent, ABT-737-induced apoptosis is often blocked
      in several types of cancer cells with elevated expression of Mcl-1. Cafestol, one
      of the major compounds in coffee beans, has been reported to have anti
      carcinogenic activity and tumor cell growth-inhibitory activity, and we examined
      whether cafestol could overcome resistance against ABT-737 in Mcl-1-overexpressed
      human renal carcinoma Caki cells. ABT-737 alone had no effect on apoptosis, but
      cafestol markedly enhanced ABT-737-mediated apoptosis in Mcl-1-overexpressed Caki
      cells, human glioma U251MG cells, and human breast carcinoma MDA-MB231 cells. By
      contrast, co-treatment with ABT-737 and cafestol did not induce apoptosis in
      normal human skin fibroblast. Furthermore, combined treatment with cafestol and
      ABT-737 markedly reduced tumor growth compared with either drug alone in
      xenograft models. We found that cafestol inhibited Mcl-1 protein expression,
      which is important for ABT-737 resistance, through promotion of protein
      degradation. Moreover, cafestol increased Bim expression, and siRNA-mediated
      suppression of Bim expression reduced the apoptosis induced by cafestol plus ABT
      737. Taken together, cafestol may be effectively used to enhance ABT-737
      sensitivity in cancer therapy via downregulation of Mcl-1 expression and
      upregulation of Bim expression. 

PMID- 25375380
TI  - PGC-1alpha buffers ROS-mediated removal of mitochondria during myogenesis.
AB  - Mitochondrial biogenesis and mitophagy are recognized as critical processes
      underlying mitochondrial homeostasis. However, the molecular pathway(s)
      coordinating the balance between these cellular programs is still poorly
      investigated. Here, we show an induction of the nuclear and mitochondrial
      peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC
      1alpha) during myogenesis, which in turn co-activates the transcription of
      nuclear and mtDNA-encoded mitochondrial genes. We demonstrate that PGC-1alpha
      also buffers oxidative stress occurring during differentiation by promoting the
      expression of antioxidant enzymes. Indeed, by downregulating PGC-1alpha, we
      observed an impairment of antioxidants expression, which was accompanied by a
      significant reactive oxygen species (ROS) burst and increase of oxidative damage
      to proteins. In parallel, we detected a decrease of mitochondrial mass and
      function as well as increased mitophagy through the ROS/FOXO1 pathway. Upon PGC
      1alpha downregulation, we found ROS-dependent nuclear translocation of FOXO1 and
      transcription of its downstream targets including mitophagic genes such as LC3
      and PINK1. Such events were significantly reverted after treatment with the
      antioxidant Trolox, suggesting that PGC-1alpha assures mitochondrial integrity by
      indirectly buffering ROS. Finally, the lack of PGC-1alpha gave rise to a decrease
      in MYOG and a strong induction of atrophy-related ubiquitin ligases FBXO32
      (FBXO32), indicative of a degenerative process. Overall, our results reveal that
      in myotubes, PGC-1alpha takes center place in mitochondrial homeostasis during
      differentiation because of its ability to avoid ROS-mediated removal of
      mitochondria. 

PMID- 25375383
TI  - One RN's experience reducing unit conflict and the use of restraint and
      seclusion.

PMID- 25375387
TI  - Pharmacogenetic testing in psychiatry: not (quite) ready for primetime.
AB  - To the extent that genetic factors are associated with the efficacy,
      tolerability, and safety of different drugs, pharmacogenetic tests may be used to
      personalize medication treatments for an individual. Pharmacogenetic tests, such
      as GeneSight Psychotropic and the Genecept Assay, are being marketed directly to
      patients and prescribers despite a relative lack of evidence to support their
      clinical validity or utility. Pharmacogenetic testing is potentially useful in
      certain clinical situations, but its usefulness will depend on the knowledge base
      of the prescriber to be able to interpret the findings for a particular patient.
      Proposed guidelines on laboratory developed tests will likely encourage, if not
      require, evidence for the clinical validity and utility of pharmacogenetic tests
      before they are approved for marketing.

PMID- 25375388
TI  - Postoperative cognitive dysfunction in older adults: a call for nursing
      involvement.
AB  - As the population continues to age and new medical developments make surgery at
      advanced ages increasingly possible, it is important to consider how older adults
      tolerate surgery and anesthesia. Considerable evidence shows that older adults
      have a higher risk of developing postoperative cognitive dysfunction (POCD),
      which leads to transient and sometimes long-term cognitive changes that may
      affect quality of life. Because little is known about how to prevent or treat
      POCD, it is important that nurses identify ways in which they can intervene to
      help patients who experience this disorder.

PMID- 25375391
TI  - Hyperresponders vs. nonresponder patients after renal denervation: do they
      differ?
AB  - BACKGROUND: Blood pressure (BP) response after renal denervation (RDN) is highly
      variable. Besides baseline BP, no reliable predictors of response have been
      consistently identified. The differences between patients showing a major BP
      decrease after RDN vs. nonresponders have not been studied so far. AIM AND
      METHODS: We identified extreme BP responders (first quintile) and nonresponders
      (fifth quintile) to RDN defined according to office or 24-h ambulatory BP in the
      European Network COordinating research on Renal Denervation database (n = 109)
      and compared the baseline characteristics and BP changes 6 months after RDN in
      both subsets. RESULTS: In extreme responders defined according to ambulatory BP,
      baseline BP and BP changes 6 months after RDN were similar for office and out-of
      the office BP. In contrast, extreme responders defined according to office BP
      were characterized by a huge white-coat effect at baseline, with dramatic
      shrinkage at 6 months. Compared with nonresponders, extreme responders defined
      according to office BP were more frequently women, had higher baseline office-
      but not ambulatory--BP, and higher estimated glomerular filtration rate (eGFR).
      In contrast, when considering ambulatory BP decrease to define extreme responders
      and nonresponders, the single relevant difference between both subsets was
      baseline ambulatory BP. CONCLUSION: This study suggests a major overestimation of
      BP response after RDN in extreme responders defined according to office, but not
      ambulatory BP. The association of lower eGFR with poor response to RDN is
      consistent with our previous analysis. The increased proportion of women in
      extreme responders may reflect sex differences in drug adherence.

PMID- 25375392
TI  - Filtering blebs using 3-dimensional anterior-segment optical coherence
      tomography: a prospective investigation.
AB  - IMPORTANCE: Posttrabeculectomy changes in bleb parameters measured using 3
      dimensional (3-D) anterior-segment optical coherence tomography (OCT) remain
      uncharacterized and might be related to postsurgical intraocular-pressure (IOP)
      control. OBJECTIVE: To evaluate time-dependent posttrabeculectomy changes in
      filtering bleb parameters using 3-D anterior-segment OCT. DESIGN, SETTING, AND
      PARTICIPANTS: This prospective observational study was conducted at Kumamoto
      University Hospital, Kumamoto, Japan. Patients with open-angle glaucoma who
      underwent uncombined fornix-based trabeculectomy at Kumamoto University Hospital
      between January 1, 2012, and October 31, 2012, were included. Twenty-nine eyes
      were enrolled, 23 of which were followed up for 1 year without additional
      glaucoma surgical procedures; 3 required additional glaucoma surgery.
      INTERVENTIONS: Imaging filtering blebs using 3-D anterior-segment OCT. MAIN
      OUTCOMES AND MEASURES: The primary end points were changes in bleb parameters
      including the position and width of the filtration openings on the scleral flap,
      the total bleb height, fluid-filled cavity height, bleb wall thickness, and bleb
      wall intensity, which were measured using 3-D anterior-segment OCT. The secondary
      end points were postsurgical IOP measured 0.5, 3, 6, and 12 months after
      trabeculectomy, and the effects of aqueous cytokine levels on the bleb
      parameters. RESULTS: We observed increased total bleb height (0.82 to 1.25 mm;
      difference: 95% CI, 0.10 to 0.75; P = .01), bleb wall thickness (0.46 to 0.61 mm;
      difference: 95% CI, 0.02 to 0.28; P = .03), and distance from the top of the
      scleral flap to the filtration opening (1.69 to 2.16 mm; difference: 95% CI, 0.28
      to 0.70; P < .001), as well as decreased width of the filtration opening (2.08 to
      1.12 mm; difference: 95% CI, -1.75 to -0.49; P = .002) between 0.5 and 12 months
      posttrabeculectomy. The filtration openings tended to close from the fornix side
      of the scleral flap during the wound healing process. Moreover, the width of the
      filtration opening at 0.5 months posttrabeculectomy correlated with the IOP at 12
      months (P = .02). The aqueous humor level of monocyte chemoattractant protein-1
      was correlated with the width of the filtration opening at 3 and 6 months
      posttrabeculectomy. CONCLUSIONS AND RELEVANCE: The width of the filtration
      opening at 0.5 months posttrabeculectomy correlated with the IOP at 12 months.
      The width of the filtration opening at the early stage may be a prognostic factor
      for long-term IOP control. Large-scale studies with longer follow-up periods are
      required.

PMID- 25375393
TI  - Low probability of initiating nirS transcription explains observed gas kinetics
      and growth of bacteria switching from aerobic respiration to denitrification.
AB  - In response to impending anoxic conditions, denitrifying bacteria sustain
      respiratory metabolism by producing enzymes for reducing nitrogen oxyanions/
      oxides (NOx) to N2 (denitrification). Since denitrifying bacteria are non
      fermentative, the initial production of denitrification proteome depends on
      energy from aerobic respiration. Thus, if a cell fails to synthesise a minimum of
      denitrification proteome before O2 is completely exhausted, it will be unable to
      produce it later due to energy-limitation. Such entrapment in anoxia is recently
      claimed to be a major phenomenon in batch cultures of the model organism
      Paracoccus denitrificans on the basis of measured e(-)-flow rates to O2 and NOx.
      Here we constructed a dynamic model and explicitly simulated actual kinetics of
      recruitment of the cells to denitrification to directly and more accurately
      estimate the recruited fraction (Fden). Transcription of nirS is pivotal for
      denitrification, for it triggers a cascade of events leading to the synthesis of
      a full-fledged denitrification proteome. The model is based on the hypothesis
      that nirS has a low probability (rden, h(-1)) of initial transcription, but once
      initiated, the transcription is greatly enhanced through positive feedback by NO,
      resulting in the recruitment of the transcribing cell to denitrification. We
      assume that the recruitment is initiated as [O2] falls below a critical threshold
      and terminates (assuming energy-limitation) as [O2] exhausts. With rden = 0.005
      h(-1), the model robustly simulates observed denitrification kinetics for a range
      of culture conditions. The resulting Fden (fraction of the cells recruited to
      denitrification) falls within 0.038-0.161. In contrast, if the recruitment of the
      entire population is assumed, the simulated denitrification kinetics deviate
      grossly from those observed. The phenomenon can be understood as a 'bet-hedging
      strategy': switching to denitrification is a gain if anoxic spell lasts long but
      is a waste of energy if anoxia turns out to be a 'false alarm'.

PMID- 25375394
TI  - Alcohol, violence, and a fast growing male population: exploring a risky-mix in
      "boomtown" Darwin.
AB  - Boomtowns are places where populations grow rapidly, mostly as a result of large
      scale natural resource developments. Increases in alcohol consumption and alcohol
      fuelled violence are often linked to influxes of (predominantly male) workers
      associated with such developments. This article provides an integrated review of
      literature concerning alcohol and violence in boomtowns. The authors aim to
      understand the links between these issues and explore how negative impacts have
      been addressed. New learning from the review is considered in the context of
      Darwin, a newly booming city in Australia's Northern Territory. The authors find
      that although alcohol-related violence is likely to increase, there is limited
      literature concerning the prevention or mitigation of negative impacts in
      boomtown contexts. The need for research, planning, and policy making involving
      all stakeholders is highlighted. 

PMID- 25375395
TI  - Physician-patient communication on cost and affordability in asthma care. Who
      wants to talk about it and who is actually doing it.
AB  - RATIONALE: Patient perceptions of financial burden and rates of cost-related
      nonadherence are high among individuals with asthma across the socioeconomic
      spectrum. Little is known about preferences and frequency of physician-patient
      discussions about cost/affordability among individuals managing respiratory
      conditions. OBJECTIVES: To examine who has a preference to discuss the cost of
      their asthma care with their physician, how often physician-patient communication
      about cost/affordability actually is occurring, and what clinical and demographic
      characteristics of patients are predictive of communication. METHODS: Data came
      from 422 African American adult women with asthma who were asked about
      communication preferences and practices around cost and affordability with their
      physician. Data were analyzed using descriptive statistics and multiple variable
      logistic regression models. MEASUREMENTS AND MAIN RESULTS: Fifty-two percent (n =
      219) of this sample perceived financial burden. Seventy-two percent (n = 300)
      reported a preference to discuss cost with their health-care provider. Thirty
      nine percent (n = 163) reported actually having a conversation with their
      physician about cost. Among the 61% who reported no discussion, 40% (n = 103)
      reported financial burden, and 55% (n = 140) reported a preference for
      discussion. Lower household income (P < 0.001), perception of financial burden (P
      < 0.001), and higher out-of-pocket expenses for medicines (P < 0.05) were
      significantly predictive of greater preference to communicate about
      cost/affordability with the doctor when adjusted for clinical and demographic
      characteristics. Perception of financial burden (P < 0.001), preference to
      discuss affordability (P < 0.001), and greater number of chronic conditions (P <
      0.001) were significantly predictive of greater likelihood of communication about
      cost/affordability with the doctor when adjusted for clinical and demographic
      characteristics. Bivariate analyses revealed that patients who reported a
      discussion of cost were more likely to report worse asthma control and lower
      asthma-related quality of life. CONCLUSIONS: An imbalance is evident between
      patients who would like to discuss cost with their doctor and those who actually
      do. Patients are interested in low-cost options and a venue for addressing their
      concerns with a care provider; therefore, a greater understanding is needed in
      how to effectively and efficiently integrate these conversations and viable
      solutions into the delivery of health care. Additional research is necessary to
      determine whether communication about the cost of therapy is associated with
      health outcomes.

PMID- 25375396
TI  - Physical activity in young adults: a signal detection analysis of Health
      Information National Trends Survey (HINTS) 2007 data.
AB  - Many young adults are insufficiently active to achieve the health benefits of
      regular physical activity. Using signal detection analysis of data from the 2007
      Health Information National Trends Survey, the authors examined distinct
      subgroups of 18-39 year-old adults who vary in their likelihood of not meeting
      physical activity recommendations. We randomly split the sample and conducted
      signal detection analysis on the exploratory half to identify subgroups and
      interactions among sociodemographic and health communication variables that
      predicted engaging in less than 150 minutes per week of moderate-intensity
      physical activity (low physical activity). We compared rates of low physical
      activity among subgroups with similarly defined subgroups in the validation
      sample. Overall, 62% of participants did not meet physical activity
      recommendations. Among 8 subgroups identified, low physical activity rates ranged
      from 31% to 90%. Predictors of low physical activity were general health, body
      mass index (BMI), perceived cancer risk, health-related Internet use, and trust
      in information sources. The least active subgroup (90% low physical activity)
      included young adults in poor to good health with a BMI of 30.8 or more (obese).
      The most active subgroup (31% low physical activity) comprised those in very good
      to excellent health, who used a website to help with diet, weight, or physical
      activity, and had little to no trust in health information on television.
      Findings suggest potential intervention communication channels and can inform
      targeted physical activity interventions for young adults. 

PMID- 25375397
TI  - Gastrointestinal adverse events of glucagon-like peptide-1 receptor agonists in
      patients with type 2 diabetes: a systematic review and network meta-analysis.
AB  - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new
      class of drugs used in the treatment of type 2 diabetes mellitus (T2DM).
      Gastrointestinal (GI) adverse events (AEs) are the most frequently reported
      treatment-related AEs for GLP-1 RAs. We aim to evaluate the effect of GLP-1 RAs
      on the incidence of GI AEs of T2DM. MATERIALS AND METHODS: The overview of the GI
      events of GLP-1 RAs has been performed on relevant publications through the
      literature search, such as MEDLINE, EMBASE, Cochrane Library, and
      ClinicalTrials.gov The manufacturer was contacted regarding unpublished data. We
      analyzed direct and indirect comparisons of different treatments using Bayesian
      network meta-analysis. RESULTS: Taspoglutide 30 mg once weekly (TAS30QW) and
      lixisenatide 30 MUg twice daily (LIX30BID) were ranked the top two drugs in terms
      of GI AEs versus placebo. The odds ratios of nausea and vomiting for TAS30QW were
      11.8 (95% confidence interval [CI], 2.89, 46.9) and 51.7 (95% CI, 7.07, 415),
      respectively, and that of diarrhea was 4.93 (95% CI, 1.75, 14.7) for LIX30BID.
      CONCLUSIONS: Our study found all GLP-1 RA dose regimens significantly increased
      the incidence of GI AEs, compared with placebo or conventional treatment. The
      occurrence of GI AEs was different with diverse dose regimens of GLP-1 RAs.
      TAS30QW had the maximum probability to occur nausea and vomiting, whereas
      LIX30BID had the maximum probability to cause development of diarrhea versus
      other treatments.

PMID- 25375399
TI  - Biofilm the challenge.

PMID- 25375400
TI  - Randomised controlled clinical trial for autologous fibroblast-hyaluronic acid
      complex in treating diabetic foot ulcers.
AB  - OBJECTIVE: Diabetic foot ulcers (DFUs) often pose a treatment problem.
      Bioengineered skin substitutes have been reported to result in accelerated
      diabetic wound healing. The purpose of this clinical trial was to evaluate the
      efficacy and safety of the autologous fibroblast-hyaluronic acid complex for
      treating DFUs. METHOD: A stratified, randomised, controlled, multicentre study
      was carried out. Patients with DFUs were allocated to either a treatment group
      with grafting of an autologous fibroblast-hyaluronic acid complex or a control
      group with non-adherent foam dressing. Except for application of the fibroblast
      complex, treatment of the study ulcers was identical for patients in both groups.
      The maximum follow-up period for each patient was 12 weeks. RESULTS: Complete
      ulcer healing was achieved in 84% (26/31 patients) of the treatment group and 34%
      (11/32 patients) of the control group (p<0.05). The times required for complete
      healing were 36.4 +/- 17.6 and 48.4 +/- 13.1 days in the treatment and control
      groups, respectively (p<0.05). No adverse events related to treatment occurred.
      CONCLUSION: These results indicate that autologous fibroblast-hyaluronic acid
      complex may offer a safe and effective treatment for DFUs.

PMID- 25375398
TI  - The Pseudomonas aeruginosa type III translocon is required for biofilm formation
      at the epithelial barrier.
AB  - Clinical infections by Pseudomonas aeruginosa, a deadly Gram-negative,
      opportunistic pathogen of immunocompromised hosts, often involve the formation of
      antibiotic-resistant biofilms. Although biofilm formation has been extensively
      studied in vitro on glass or plastic surfaces, much less is known about biofilm
      formation at the epithelial barrier. We have previously shown that when added to
      the apical surface of polarized epithelial cells, P. aeruginosa rapidly forms
      cell-associated aggregates within 60 minutes of infection. By confocal microscopy
      we now show that cell-associated aggregates exhibit key characteristics of
      biofilms, including the presence of extracellular matrix and increased resistance
      to antibiotics compared to planktonic bacteria. Using isogenic mutants in the
      type III secretion system, we found that the translocon, but not the effectors
      themselves, were required for cell-associated aggregation on the surface of
      polarized epithelial cells and at early time points in a murine model of acute
      pneumonia. In contrast, the translocon was not required for aggregation on
      abiotic surfaces, suggesting a novel function for the type III secretion system
      during cell-associated aggregation. Supernatants from epithelial cells infected
      with wild-type bacteria or from cells treated with the pore-forming toxin
      streptolysin O could rescue aggregate formation in a type III secretion mutant,
      indicating that cell-associated aggregation requires one or more host cell
      factors. Our results suggest a previously unappreciated function for the type III
      translocon in the formation of P. aeruginosa biofilms at the epithelial barrier
      and demonstrate that biofilms may form at early time points of infection. 

PMID- 25375401
TI  - Clinical evaluation of a thin absorbent skin adhesive dressing for wound
      management.
AB  - OBJECTIVE: This article assesses the use of BeneHold Thin Absorbent Skin Adhesive
      (TASA) wound dressings in a large UK primary care organisation. These wound
      dressings are thin (0.12 mm), breathable, transparent, and are able to absorb and
      retain wound exudate. This non-comparative evaluation was undertaken to explore
      the clinical advantages this differentiated combination of physical properties
      offered. METHOD: The dressings are CE-marked medical devices, and were used on
      patients with acute and chronic wounds that were assessed and classified as light
      to moderately exuding. Clinical performance was evaluated with respect to the
      dressing's ease of use (application and removal, conformability, mould-ability,
      rolling and edge-lift), debridement, protection of the peri-wound, wear time,
      fluid handling, wound bed residue, visibility of the wound, and clinical
      acceptability. The evaluating clinicians used an agreed audit tool to collect
      data from case reports to document the progression of wounds of various
      aetiologies, including chronic and acute, for a maximum period of four weeks.
      Qualitative feedback on dressing performance was also collected at the
      evaluation's end, both from the clinicians' and patients' perspectives Results:
      Some 15 patients were assessed. The wear time was up to seven days in many cases,
      and on average was 3.9 days longer than their previous dressings. Clinicians
      perceived that wounds progressed toward healing in all but two cases, where the
      wounds remained unchanged. Out of five cases where wounds presented with
      necrosis, all underwent significant autolytic debridement underneath the new
      dressings. Transparency was a noted benefit from both the clinicians' and
      patients' perspectives because it enabled continuous monitoring of the full wound
      bed and peri-wound skin without the need to disrupt the dressing. CONCLUSION: The
      dressing was well-received by both clinicians and patients in all fifteen cases.
      The thin absorbent skin adhesive dressing was found to be a promising new
      technology that could offer significant advantages to improve the quality, cost,
      and convenience of wound care. Further work is underway to validate these
      findings in larger and more homogeneous patient groups.

PMID- 25375402
TI  - Influence of superabsorbent dressings on non-healing ulcers: a multicentre case
      series from the Netherlands and the UK.
AB  - OBJECTIVE: To record and assess the application and the progression of wound
      healing in patients who received Sorbion sachet S or Sorbion Sana wound
      dressings. METHOD: A convenience sample of patients with chronic wounds was
      recruited from nursing homes or community wound clinics in the Netherlands and
      the UK. Wound surface area measurements, pain assessment using a visual analogue
      scale score, patient affect (mood) and social interaction were recorded using a
      specifically designed evaluation template. RESULTS: Pressure ulcer (PU) (n=11)
      and leg ulcer (LU) (n=20) patients had a mean age of 64.6 years and 71.7 years,
      respectively. Mean PU surface area decreased from 15.27 cm2 in week 0 to 7.63 cm2
      in week 8, while mean LU surface area decreased from 19.43 cm2 in week 0 to 7.19
      cm2 in week 8. Mean PU pain decreased from 3.69 in week 0 to 0.67 in week 8,
      while pain at dressing change decreased from 3.23 in week 0 to 0.75 in week 8.
      Furthermore, mean LU pain decreased from 3.45 in week 0 to 1.90 in week 8, and
      pain at dressing change decreased from 3.4 in week 0 to 1.3 in week 8. The number
      of patients experiencing a negative influence of the PU on affect reduced from 6
      in week 0 to 2 in week 8 and on social interaction from 6 in week 0 to 2 in week
      8. The number of patients experiencing a negative influence of their LU on affect
      reduced from 7 in week 0 to zero in week 8 and on social interaction from 7 in
      week 0 to 2 in week 8. CONCLUSION: This case series records the response of
      patients' chronic wounds in terms of wound progress, patient pain and additional
      psycho-social factors following the application of the superabsorbent dressings
      and indicates that the dressings have a positive role to play in creating an
      environment conductive to the promotion of healing in LUs and PUs.

PMID- 25375403
TI  - Reconciling increasing wound care demands with available resources.
AB  - Demographic and epidemiological data suggest that health-care demand will
      increase considerably in the future as a result of an ageing population and a
      rise in the prevalence of chronic diseases such as diabetes. This phenomenon has
      come to be referred to as the 'health care time bomb' in the popular press and
      political discourse. The authors seek to look beyond the headlines and political
      rhetoric to clarify the extent to which they reflect the likely future reality
      with a specific focus on wound management. The present-day burden that wounds and
      current wound management practices place upon the health-care system are detailed
      and clarified, and the potential future implications of increasing wound
      prevalence on the current picture are explored. Possible opportunities to enhance
      current wound management practice as identified in the analysis are discussed.

PMID- 25375404
TI  - Operative management of acute pavement burns: a case series.
AB  - OBJECTIVE: Acute burns suffered from contact with environmentally heated roadways
      and walkways are a rare entity. The aim of this report is to assess the
      information gained from the treatment of a series of patients. METHOD: A
      retrospective review of a consecutive series of cases, where operative treatment
      was necessary, that occurred during July 2010 in southern Arizona. RESULTS: Seven
      patients were included, with an average total body surface area burn of 10.2%.
      Direct fascial excision and tangential excision were carried out on three and
      four patients, respectively. Although tangential excision was carried out to
      normal endpoints, there was commonly a need for repetitive debridement. The total
      hospital costs were over $4,400,000 (L2,730,000). CONCLUSION: Burns suffered from
      contact with roadways/walkways are often deeper than suggested by their
      appearance. Direct fascial excision minimises the number of debridement sessions.
      We hypothesise that the failure to offload pressure on these wounds may be a
      causative factor in their observed deepening.

PMID- 25375405
TI  - Biofilms in wounds: a review of present knowledge.
AB  - Following confirmation of the presence of biofilms in chronic wounds, the term
      biofilm became a buzzword within the wound healing community. For more than a
      century pathogens have been successfully isolated and identified from wound
      specimens using techniques that were devised in the nineteenth century by Louis
      Pasteur and Robert Koch. Although this approach still provides valuable
      information with which to help diagnose acute infections and to select
      appropriate antibiotic therapies, it is evident that those organisms isolated
      from clinical specimens with the conditions normally used in diagnostic
      laboratories are mainly in a planktonic form that is unrepresentative of the way
      in which most microbial species exist naturally. Usually microbial species adhere
      to each other, as well as to living and non-living surfaces, where they form
      complex communities surrounded by collectively secreted extracellular polymeric
      substances (EPS). Cells within such aggregations (or biofilms) display varying
      physiological and metabolic properties that are distinct from those of planktonic
      cells, and which contribute to their persistence. There are many factors that
      influence healing in wounds and the discovery of biofilms in chronic wounds has
      provided new insight into the reasons why. Increased tolerance of biofilms to
      antimicrobial agents explains the limited efficacy of antimicrobial agents in
      chronic wounds and illustrates the need to develop new management strategies.
      This review aims to explain the nature of biofilms, with a view to explaining
      their impact on wounds. 

PMID- 25375406
TI  - An estimate of the potential budget impact of using prophylactic dressings to
      prevent hospital-acquired PUs in Australia.
AB  - OBJECTIVE: To estimate the potential cost saving to the Australian health-care
      system of introducing the use of prophylactic dressings to prevent hospital
      acquired pressure ulcers (PUs) for patients with a high-risk developing a PU.
      METHOD: We estimated the costs of pressure ulceration based on conservative
      estimates of an incidence rate of 13% within 10% of the total admitted Australian
      patient population. RESULTS from a recent large randomised control trial of
      prophylactic dressing used to prevent PUs in high-risk patients were then
      extrapolated to this population to derive a potential national cost/benefit
      calculation. RESULTS: Our estimate revealed that within the high-risk population
      of acute hospitals, more than 71,000 patients could be expected to develop a PU
      annually costing AU$77,800,000 (L43,000,000). Whereas by implementing a national
      PU prevention initiative based on the use of prophylactic multilayer silicone
      foam dressings for high-risk patients, an annual saving of AU$34,800,000
      (L19,700,000) could be achieved, which represents a cost benefit of 55% to the
      Australian health-care system. CONCLUSION: Our estimate of the potential cost
      benefit of implementing the use of prophylactic dressings to prevent hospital
      acquired PUs in high-risk patients uses conservative estimates of both the
      incidence rates of ulceration and of treatment costs. However, this is also based
      on one of the largest reported randomised control trials of this technique to
      prevent PUs. We believe that our modelling is robust yet requires replication in
      other countries with different health-care systems and costing structures.

PMID- 25375407
TI  - The combined use of NPWT and instillation using an octenidine based wound rinsing
      solution: a case study.
AB  - Effective wound bed preparation is an essential element in the healing of chronic
      wounds, including pressure ulcers (PUs). Negative pressure wound therapy (NPWT)
      reduces oedema, stimulates the formation of granulation tissue and helps remove
      wound exudate. This helps prepare the wound bed for secondary healing, skin
      grafting or coverage with flaps. Combining NPWT with an instillation phase using
      an antiseptic (octenidine based) irrigation solution is a novel approach to PU
      management. Three patients with Category 4 gluteal PUs were treated with NPWT and
      instillation fluid, following surgical debridement of necrotic tissue. The aim
      was to achieve optimal wound bed preparation prior to wound closure by local
      fasciocutaneous flap. The antiseptic efficacy of octenilin wound irrigation
      solution in microorganism eradication was quantified by in vitro tests simulating
      real conditions using leg ulcer vacuum exudates. All wounds completely healed
      after four weeks, and no adverse incidents occurred due to instillation of
      octenidine. No recurrence of the PU occurred during a one year follow-up.

PMID- 25375409
TI  - Entropy-mediated mechanical response of the interfacial nanoparticle patterning.
AB  - The precise organization of nano-objects into well-defined patterns at interfaces
      is an outstanding challenge in the field of nanocomposites toward technologically
      important materials and devices. Herein, by means of computer simulations we show
      novel mechanomutable nanocomposites designed by binary mixtures of tethered Janus
      nanoparticles at the interface of a binary fluid mixture under mechanical
      pressure. Our simulations demonstrate that the nanoparticle organization in the
      systems undergo reversible transition between random state and long-ranged
      intercalation state, controlled by various structural parameters of the tethered
      chains and the applied pressure. The dynamical mechanism during the transition is
      explored through examining the diffusion trajectories of the nanoparticles
      confined at the interfaces. We provide a theoretical analysis of the lateral
      pressure induced by the tethered chains, which is fully supported by simulation
      data and reveals that the compression-induced transition is fundamentally
      attributed to the entropic effect from the tethered chains. Our study leads to a
      class of interface-reactive nanomaterials in which the transfer and recovery of
      interfacial nanopatterning presents precise and tunable mechanical responses. 

PMID- 25375408
TI  - Toll-like receptor 4 (TLR4) antagonist eritoran tetrasodium attenuates liver
      ischemia and reperfusion injury through inhibition of high-mobility group box
      protein B1 (HMGB1) signaling.
AB  - Toll-like receptor 4 (TLR4) is ubiquitously expressed on parenchymal and immune
      cells of the liver and is the most studied TLR responsible for the activation of
      proinflammatory signaling cascades in liver ischemia and reperfusion (I/R). Since
      pharmacological inhibition of TLR4 during the sterile inflammatory response of
      I/R has not been studied, we sought to determine whether eritoran, a TLR4
      antagonist trialed in sepsis, could block hepatic TLR4-mediated inflammation and
      end organ damage. When C57BL/6 mice were pretreated with eritoran and subjected
      to warm liver I/R, there was significantly less hepatocellular injury compared to
      control counterparts. Additionally, we found that eritoran is protective in liver
      I/R through inhibition of high-mobility group box protein B1 (HMGB1)-mediated
      inflammatory signaling. When eritoran was administered in conjunction with
      recombinant HMGB1 during liver I/R, there was significantly less injury,
      suggesting that eritoran blocks the HMGB1-TLR4 interaction. Not only does
      eritoran attenuate TLR4-dependent HMGB1 release in vivo, but this TLR4 antagonist
      also dampened HMGB1's release from hypoxic hepatocytes in vitro and thereby
      weakened HMGB1's activation of innate immune cells. HMGB1 signaling through TLR4
      makes an important contribution to the inflammatory response seen after liver
      I/R. This study demonstrates that novel blockade of HMGB1 by the TLR4 antagonist
      eritoran leads to the amelioration of liver injury. 

PMID- 25375410
TI  - NMR flow tube for online NMR reaction monitoring.
AB  - In this paper we describe the development of a 5 mm NMR flow tube that can be
      used in a standard 5 mm NMR probe, enabling the user to conduct experiments on
      flowing samples or, more specifically, on flowing reaction mixtures. This enables
      reaction monitoring or kinetic experiments to be conducted by flowing reaction
      mixtures from a reaction vessel to detection in the coil area of the NMR, without
      the need for a specialized flow NMR probe. One of the key benefits of this flow
      tube is that it provides flexibility to be used across a range of available
      spectrometers of varying magnetic field strengths with a standard 5 mm probe
      setup. The applicability of this flow tube to reaction monitoring is demonstrated
      using the reaction of p-phenylenediamine and isobutyraldehyde to form the diimine
      product. 

PMID- 25375412
TI  - Uptake of epoxydiol isomers accounts for half of the particle-phase material
      produced from isoprene photooxidation via the HO2 pathway.
AB  - The oxidation of isoprene is a globally significant source of secondary organic
      material (SOM) of atmospheric particles. The relative importance of different
      parallel pathways, however, remains inadequately understood and quantified. SOM
      production from isoprene photooxidation was studied under hydroperoxyl-dominant
      conditions for <5% relative humidity and at 20  degrees C in the presence of
      highly acidic to completely neutralized sulfate particles. Isoprene
      photooxidation was separated from SOM production by using two continuously mixed
      flow reactors connected in series and operated at steady state. Two online mass
      spectrometers separately sampled the gas and particle phases in the reactor
      outflow. The loss of specific gas-phase species as contributors to the production
      of SOM was thereby quantified. The produced SOM mass concentration was directly
      proportional to the loss of isoprene epoxydiol (IEPOX) isomers from the gas
      phase. IEPOX isomers lost from the gas phase accounted for (46 +/- 11)% of the
      produced SOM mass concentration. The IEPOX isomers comprised (59 +/- 21)%
      (molecular count) of the loss of monitored gas-phase species. The implication is
      that for the investigated reaction conditions the SOM production pathways tied to
      IEPOX isomers accounted for half of the SOM mass concentration. 

PMID- 25375413
TI  - Influence of calcium(II) and chloride on the oxidative reactivity of a
      manganese(II) complex of a cross-bridged cyclen ligand.
AB  - Available data from different laboratories have confirmed that both Ca(2+) and
      Cl(-) are crucial for water oxidation in Photosystem II. However, their roles are
      still elusive. Using a manganese(II) complex having a cross-bridged cyclen ligand
      as a model, the influence of Ca(2+) on the oxidative reactivity of the
      manganese(II) complex and its corresponding manganese(IV) analogue were
      investigated. It has been found that adding Ca(2+) can significantly improve the
      oxygenation efficiency of the manganese(II) complex in sulfide oxidation and
      further accelerate the oxidation of sulfoxide to sulfone. Similar improvements
      have also been observed for Mg(2+), Sr(2+), and Ba(2+). A new monomeric
      manganese(IV) complex having two cis-hydroxide ligands has also been isolated
      through oxidation of the corresponding manganese(II) complex with H2O2 in the
      presence of NH4PF6. This rare cis-dihydroxomanganese(IV) species has been well
      characterized by X-ray crystallography, electrochemistry, electron paramagnetic
      resonance, and UV-vis spectroscopy. Notably, using the manganese(IV) complex as a
      catalyst demonstrates higher activity than the corresponding manganese(II)
      complex, and adding Ca(2+) further improves its catalytic efficiency. However,
      adding Cl(-) decreases its catalytic activity. In electrochemical studies of
      manganese(IV) complexes with no chloride ligand present, adding Ca(2+) positively
      shifted the redox potential of the Mn(IV)/Mn(III) couple but negatively shifted
      its Mn(V)/Mn(IV) couple. In the manganese(II) complex having a chloride ligand,
      adding Ca(2+) shifted both the Mn(IV)/Mn(III) and Mn(V)/Mn(IV) couples in the
      negative direction. The revealed oxidative reactivity and redox properties of the
      manganese species affected by Ca(2+) and Cl(-) may provide new clues to
      understanding their roles in the water oxidation process of Photosystem II. 

PMID- 25375414
TI  - Role of massage in preventing formation of papules and nodules after injecting
      poly-L-lactic acid.

PMID- 25375415
TI  - Modalities and prescribing strategies in intensive home hemodialysis: a narrative
      review.
AB  - Over the past decades, evidence on the benefits of intensive hemodialysis, more
      frequent and longer comparing to conventional hemodialysis, has emerged. The home
      environment is an ideal setting to perform intensive hemodialysis without the
      reliance on organizational and structural needs. The observed benefits of
      frequent hemodialysis have resulted in a rise in prevalent intensive home
      hemodialysis patients around the world. A successful home hemodialysis program
      requires a well-structured predialysis education program with focus on home
      dialysis and a dedicated multidisciplinary team with knowledge about the
      specifics of home hemodialysis and with a holistic approach to provide optimal
      care. In this narrative review, we describe different modalities of home
      hemodialysis and dialysis prescription specifics of intensive nocturnal
      hemodialysis, the modality with overall best outcomes. 

PMID- 25375416
TI  - In Vitro Assessment of Human Islet Vulnerability to Instant Blood-Mediated
      Inflammatory Reaction (IBMIR) and Its Use to Demonstrate a Beneficial Effect of
      Tissue Culture.
AB  - Culture of human pancreatic islets is now routinely carried out prior to clinical
      islet allotransplantation, using conditions that have been developed empirically.
      One of the major causes of early islet destruction after transplantation is the
      process termed instant blood-mediated inflammatory reaction (IBMIR). The aim of
      this study was to develop in vitro methods to investigate IBMIR and apply them to
      the culture conditions used routinely in our human islet isolation laboratory.
      Freshly isolated or precultured (24 h, 48 h) human islets were incubated in
      either ABO-compatible allogeneic human blood or Hank's buffered salt solution
      (HBSS) for 1 h at 37 degrees C. Tissue factor (TF) expression and leukocyte
      migration were assessed by light microscopy. TF was also quantified by ELISA. To
      assess beta-cell function, glucose-stimulated insulin secretion (GSIS) assay was
      carried out. The extent of islet beta-cell damage was quantified using a
      proinsulin assay. Islets cultured for 24 h had higher GSIS when compared to
      freshly isolated or 48-h precultured islets. Freshly isolated islets had
      significantly higher TF content than 24-h and 48-h precultured islets. Incubation
      of freshly isolated human islets in allogeneic human blood released 6.5-fold
      higher level of proinsulin in comparison to freshly isolated human islets in
      HBSS. The high level of proinsulin released was significantly attenuated when
      precultured islets (24 h or 48 h) were exposed to fresh blood. Histological
      examination of fresh islets in blood clot showed that some islets were
      fragmented, showing signs of extraislet insulin leakage and extensive neutrophil
      infiltration and necrosis. These features were markedly reduced when the islets
      were cultured for 24 h. These results suggest that our standard 24-h islet
      culture is markedly beneficial in attenuating IBMIR, as evidenced by increased
      GSIS, lower content of TF, decrease islet fragmentation, and proinsulin release. 

PMID- 25375417
TI  - Biofunctionalization of Si(111)7*7 by "renewable" L-cysteine transitional layer.
AB  - Surface functionalization of an inorganic surface with bio-organic molecules is
      often aimed at creating a "permanent" bio-organic surface with receptor
      functional groups. We show here that L-cysteine can be used to transform a highly
      reactive Si(111)7*7 surface to not just a permanent bio-organic surface but also
      a semipermanent (or renewable) and a temporary bio-organic surfaces by
      manipulating the exposure. In the early growth stage, the strong bonding between
      the first cysteine adlayer and the Si substrate through Si-N or Si-S linkages in
      unidentate or bidentate arrangement provides permanent biofunctionalization by
      this interfacial layer. This interfacial layer can be used to build a
      transitional layer (second adlayer) mediated by interlayer vertical hydrogen
      bonding between an amino group and a carboxylic acid group. Further exposure of
      cysteine eventually leads to a zwitterionic multilayer film involving
      electrostatic interactions between cation (-NH3(+)) and anion moieties (-COO(-)).
      The interlayer hydrogen bonding therefore provides temporary trapping of bio
      organic molecules as the second transitional layer that is stable up to 175 
      degrees C. This transitional layer can be easily removed by annealing above this
      temperature and then regenerated with the same molecular layer or a different one
      by "renewing" the interlayer hydrogen bonds. We also illustrate coverage
      dependent adsorption structures of cysteine, from bidentate to unidentate
      attachments and to self-assembled multimers, involving formation of intralayer
      horizontal N...H-O hydrogen bonds, by combining our X-ray photoemission data with
      the local density-of-state images obtained by scanning tunnelling microscopy.

PMID- 25375420
TI  - Unusual eigenvalue spectrum and relaxation in the Levy-Ornstein-Uhlenbeck
      process.
AB  - We consider the rates of relaxation of a particle in a harmonic well, subject to
      Levy noise characterized by its Levy index MU. Using the propagator for this Levy
      Ornstein-Uhlenbeck process (LOUP), we show that the eigenvalue spectrum of the
      associated Fokker-Planck operator has the form (n+mMU)nu where nu is the force
      constant characterizing the well, and n,m?N. If MU is irrational, the eigenvalues
      are all nondegenerate, but rational MU can lead to degeneracy. The maximum
      degeneracy is shown to be 2. The left eigenfunctions of the fractional Fokker
      Planck operator are very simple while the right eigenfunctions may be obtained
      from the lowest eigenfunction by a combination of two different step-up
      operators. Further, we find that the acceptable eigenfunctions should have the
      asymptotic behavior |x|(-n1-n2MU) as |x|->infinity, with n1 and n2 being positive
      integers, though this condition alone is not enough to identify them uniquely. We
      also assert that the rates of relaxation of LOUP are determined by the
      eigenvalues of the associated fractional Fokker-Planck operator and do not depend
      on the initial state if the moments of the initial distribution are all finite.
      If the initial distribution has fat tails, for which the higher moments diverge,
      one can have nonspectral relaxation, as pointed out by et al. [Phys. Rev. Lett.
      110, 150602 (2013)].

PMID- 25375421
TI  - Spectral order statistics of Gaussian random matrices: large deviations for
      trapped fermions and associated phase transitions.
AB  - We compute the full order statistics of a one-dimensional gas of spinless
      fermions (or, equivalently, hard bosons) in a harmonic trap at zero temperature,
      including its large deviation tails. The problem amounts to computing the
      probability distribution of the kth smallest eigenvalue lambda(k) of a large
      dimensional Gaussian random matrix. We find that this probability behaves for
      large N as P[lambda(k)=x]~exp[-betaN(2)psi(k/N,x)], where beta is the Dyson index
      of the ensemble. The rate function psi(c,x), computed explicitly as a function of
      x in terms of the intensive label c=k/N, has a quadratic behavior modulated by a
      weak logarithmic singularity at its minimum. This is shown to be related to phase
      transitions in the associated Coulomb gas problem. The connection with statistics
      of extreme eigenvalues and order stastistics of random matrices is also
      discussed. We find that, as a function of c and keeping the value of x fixed, the
      rate function psi(c,x) describes the statistics of the shifted index number,
      generalizing known results on its typical fluctuations; as a function of x and
      keeping the fraction c=k/N fixed, the rate function psi(c,x) also describes the
      statistics of the kth eigenvalue in the bulk, generalizing as well the results on
      its typical fluctuations. Moreover, for k=1 (respectively, for k=N), the rate
      function captures both the fluctuations to the left and to the right of the
      typical value of lambda(1) (respectively, of lambda(N)).

PMID- 25375422
TI  - Poiseuille flow of soft glasses in narrow channels: from quiescence to steady
      state.
AB  - Using numerical simulations, the onset of Poiseuille flow in a confined soft
      glass is investigated. Starting from the quiescent state, steady flow sets in at
      a time scale which increases with a decrease in applied forcing. At this onset
      time scale, a rapid transition occurs via the simultaneous fluidization of
      regions having different local stresses. In the absence of steady flow at long
      times, creep is observed even in regions where the local stress is larger than
      the bulk yielding threshold. Finally, we show that the time scale to attain
      steady flow depends strongly on the history of the initial state. 

PMID- 25375423
TI  - Phase separation of fluids in porous media: a molecular dynamics study.
AB  - We present comprehensive molecular dynamics results for phase-separation kinetics
      of fluids in a porous medium. This system is modeled by a symmetric Lennard-Jones
      fluid mixture with a quenched random field. The presence of disorder slows down
      domain growth from power-law to a logarithmic form. It also modifies the
      correlation functions and structure factors which characterize the morphology. In
      particular, the structure-factor tail shows a non-Porod behavior, which is the
      consequence of scattering from rough interfaces. 

PMID- 25375424
TI  - Single-molecule diffusion in freely suspended smectic films.
AB  - We present a study of the molecular diffusion in freely suspended smectic-A
      liquid crystal films with thicknesses ranging from 20 down to only two molecular
      layers. The molecular mobility is directly probed by determining the trajectories
      of single, fluorescent tracer molecules. We demonstrate, using several different
      smectic compounds, that a monotonic increase of the diffusion coefficient with
      decreasing film thickness is a general phenomenon. In two-layer films, the
      diffusion is enhanced by a factor of 3 to 5 compared to the corresponding bulk
      smectic phase. Molecular dynamics simulations of freely suspended smectic films
      are presented which support the experimental results. 

PMID- 25375425
TI  - Reaction-diffusion-advection equation in binary tree networks and optimal size
      ratio.
AB  - A simple reaction-diffusion-advection equation is proposed in a dichotomous tree
      network to discuss an optimal network. An optimal size ratio r is evaluated by
      the principle of maximization of total reaction rate. In the case of reaction
      limited conditions, the optimal ratio can be larger than (1/2)(1/3) for a fixed
      value of branching number n, which is consistent with observations in mammalian
      lungs. We find furthermore that there is an optimal branching number nc when the
      Peclet number is large. Under the doubly optimal conditions with respect to the
      size ratio and branching number, the optimal value of r is close to (1/2)(1/3).

PMID- 25375426
TI  - Transition from dissipative to conservative dynamics in equations of
      hydrodynamics.
AB  - We show, by using direct numerical simulations and theory, how, by increasing the
      order of dissipativity (alpha) in equations of hydrodynamics, there is a
      transition from a dissipative to a conservative system. This remarkable result,
      already conjectured for the asymptotic case alpha->infinity [U. Frisch et al.,
      Phys. Rev. Lett. 101, 144501 (2008)], is now shown to be true for any large, but
      finite, value of alpha greater than a crossover value alphacrossover. We thus
      provide a self-consistent picture of how dissipative systems, under certain
      conditions, start behaving like conservative systems and hence elucidate the
      subtle connection between equilibrium statistical mechanics and out-of
      equilibrium turbulent flows.

PMID- 25375427
TI  - Bathtub vortex induced by instability.
AB  - The driving mechanism and the swirl direction of the bathtub vortex are
      investigated by the linear stability analysis of the no-vortex flow as well as
      numerical simulations. We find that only systems having plane symmetries with
      respect to vertical planes deserve research for the swirl direction. The bathtub
      vortex appearing in a vessel with a rectangular cross section having a drain hole
      at the center of the bottom is proved to be induced by instability when the flow
      rate exceeds a threshold. The Coriolis force is capable of determining the swirl
      direction to be cyclonic. 

PMID- 25375428
TI  - Magnetic helicity and the evolution of decaying magnetohydrodynamic turbulence.
AB  - Ensemble-averaged high resolution direct numerical simulations of reverse
      spectral transfer are presented, extending on the many single realization
      numerical studies done up to now. This identifies this type of spectral transfer
      as a statistical property of magnetohydrodynamic turbulence and thus permits
      reliable numerical exploration of its dynamics. The magnetic energy decay
      exponent from these ensemble runs has been determined to be nE=(0.47+/
      0.03)+(13.9+/-0.8)/Rlambda for initially helical magnetic fields. We show that
      even after removing the Lorentz force term in the momentum equation, thus
      decoupling it from the induction equation, reverse spectral transfer still
      persists. The induction equation is now linear with an externally imposed
      velocity field, thus amenable to numerous analysis techniques. A new door has
      opened for analyzing reverse spectral transfer, with various ideas discussed.

PMID- 25375429
TI  - Frequency spectra of turbulent thermal convection with uniform rotation.
AB  - The frequency spectra of the entropy and kinetic energy along with the power
      spectrum of the thermal flux are computed from direct numerical simulations for
      turbulent Rayleigh-Benard convection with uniform rotation about a vertical axis
      in low-Prandtl-number fluids (Pr<0.6). Simulations are done for convective Rossby
      numbers Ro>=0.2. The temporal fluctuations of these global quantities show two
      scaling regimes: (i) omega(-2) at higher frequencies for all values of Ro and
      (ii) omega(-gamma1) at intermediate frequencies with gamma1~4 for Ro>1, while
      4<gamma1<6.6 for 0.2<=Ro<1.

PMID- 25375430
TI  - Enhanced collisionless shock formation in a magnetized plasma containing a
      density gradient.
AB  - Two-dimensional hybrid simulations of super-Alfvenic expanding debris plasma
      interacting with an inhomogeneous ambient plasma are presented. The simulations
      demonstrate improved collisionless coupling of energy to the ambient ions when
      encountering a density gradient. Simulations of an expanding cylinder running
      into a step function gradient are performed and compared to a simple analytical
      theory. Magnetic flux probe data from a laboratory shock experiment are compared
      to a simulation with a more realistic debris expansion and ambient ion density.
      The simulation confirms that a shock is formed and propagates within the high
      density region of ambient plasma. 

PMID- 25375431
TI  - Dynamics of charge clouds ejected from laser-induced warm dense gold nanofilms.
AB  - We report a systematic study of the ejected charge dynamics surrounding laser
      produced 30-nm warm dense gold films using single-shot femtosecond electron
      shadow imaging and deflectometry. The results reveal a two-step dynamical process
      of the ejected electrons under high pump fluence conditions: an initial emission
      and accumulation of a large amount of electrons near the pumped surface region,
      followed by the formation of hemispherical clouds of electrons on both sides of
      the film, which escape into the vacuum at a nearly isotropic and constant
      velocity with an unusually high kinetic energy of more than 300 eV. We also
      developed a model of the escaping charge distribution that not only reproduces
      the main features of the observed charge expansion dynamics but also allows us to
      extract the number of ejected electrons remaining in the cloud. 

PMID- 25375432
TI  - Nonequilibrium scaling explorations on a two-dimensional Z(5)-symmetric model.
AB  - We have investigated the dynamic critical behavior of the two-dimensional Z(5)
      symmetric spin model by using short-time Monte Carlo (MC) simulations. We have
      obtained estimates of some critical points in its rich phase diagram and
      included, among the usual critical lines the study of first-order (weak)
      transition by looking into the order-disorder phase transition. In addition, we
      also investigated the soft-disorder phase transition by considering empiric
      methods. A study of the behavior of beta/nuz along the self-dual critical line
      has been performed and special attention has been devoted to the critical
      bifurcation point, or Fateev-Zamolodchikov (FZ) point. First, by using a
      refinement method and taking into account simulations out of equilibrium, we were
      able to localize parameters of this point. In a second part of our study, we
      turned our attention to the behavior of the model at the early stage of its time
      evolution in order to find the dynamic critical exponent z as well as the static
      critical exponents beta and nu of the FZ point on square lattices. The values of
      the static critical exponents and parameters are in good agreement with the exact
      results, and the dynamic critical exponent z~2.28 very close to the four-state
      Potts model (z~2.29). 

PMID- 25375433
TI  - Large-deviation properties of Brownian motion with dry friction.
AB  - We investigate piecewise-linear stochastic models with regard to the probability
      distribution of functionals of the stochastic processes, a question that occurs
      frequently in large deviation theory. The functionals that we are looking into in
      detail are related to the time a stochastic process spends at a phase space point
      or in a phase space region, as well as to the motion with inertia. For a Langevin
      equation with discontinuous drift, we extend the so-called backward Fokker-Planck
      technique for non-negative support functionals to arbitrary support functionals,
      to derive explicit expressions for the moments of the functional. Explicit
      solutions for the moments and for the distribution of the so-called local time,
      the occupation time, and the displacement are derived for the Brownian motion
      with dry friction, including quantitative measures to characterize deviation from
      Gaussian behavior in the asymptotic long time limit. 

PMID- 25375434
TI  - Avalanches and hysteresis in frustrated superconductors and XY spin glasses.
AB  - We study avalanches along the hysteresis loop of long-range interacting spin
      glasses with continuous XY symmetry, which serves as a toy model of granular
      superconductors with long-range and frustrated Josephson couplings. We identify
      sudden jumps in the T=0 configurations of the XY phases as an external field is
      increased. They are initiated by the softest mode of the inverse susceptibility
      matrix becoming unstable, which induces an avalanche of phase updates (or spin
      alignments). We analyze the statistics of these events and study the correlation
      between the nonlinear avalanches and the soft mode that initiates them. We find
      that the avalanches follow the directions of a small fraction of the softest
      modes of the inverse susceptibility matrix, similarly as was found in avalanches
      in jammed systems. In contrast to the similar Ising spin glass (Sherrington
      Kirkpatrick) studied previously, we find that avalanches are not distributed with
      a scale-free power law but rather have a typical size which scales with the
      system size. We also observe that the Hessians of the spin-glass minima are not
      part of standard random matrix ensembles as the lowest eigenvector has a fractal
      support. 

PMID- 25375435
TI  - Generalized dynamic scaling for quantum critical relaxation in imaginary time.
AB  - We study the imaginary-time relaxation critical dynamics of a quantum system with
      a vanishing initial correlation length and an arbitrary initial order parameter
      M0. We find that in quantum critical dynamics, the behavior of M0 under scale
      transformations deviates from a simple power law, which was proposed for very
      small M0 previously. A universal characteristic function is then suggested to
      describe the rescaled initial magnetization, similar to classical critical
      dynamics. This characteristic function is shown to be able to describe the
      quantum critical dynamics in both short- and long-time stages of the evolution.
      The one-dimensional transverse-field Ising model is employed to numerically
      determine the specific form of the characteristic function. We demonstrate that
      it is applicable as long as the system is in the vicinity of the quantum critical
      point. The universality of the characteristic function is confirmed by numerical
      simulations of models belonging to the same universality class.

PMID- 25375436
TI  - Non-Gaussian rotational diffusion in heterogeneous media.
AB  - We employ a simple model for rotational diffusivity DR of dumbbells in porous
      media in order to study spatially heterogeneous and non-Gaussian dynamics at
      Fickian time scales. We obtain the distribution P(DR) of DR's of single dumbbells
      for both ergodic and nonergodic systems. When a pore percolating network
      disappears beyond the pore percolation transition and the rotational dynamics
      becomes nonergodic, each single dumbbell undergoes Gaussian rotational dynamics
      but with different DR, which depends solely on the local pore structure. We also
      construct a map of heterogeneous dynamic regions and illustrate that such
      seemingly Fickian but non-Gaussian dynamics could be understood as the linear
      combination of the Gaussian rotational displacement distribution functions of
      each dumbbell. With a percolating pore network, the rotational dynamics becomes
      ergodic, and P(DR) is a delta function at the average value of DR.

PMID- 25375437
TI  - Short-range correlations in percolation at criticality.
AB  - We derive the critical nearest-neighbor connectivity gn as 3/4, 3(7-9pc(tri))/4(5
      4pc(tri)), and 3(2+7pc(tri))/4(5-pc(tri)) for bond percolation on the square,
      honeycomb, and triangular lattice, respectively, where pc(tri)=2sin(pi/18) is the
      percolation threshold for the triangular lattice, and confirm these values via
      Monte Carlo simulations. On the square lattice, we also numerically determine the
      critical next-nearest-neighbor connectivity as gnn=0.6875000(2), which confirms a
      conjecture by Mitra and Nienhuis [J. Stat. Mech. (2004) P10006], implying the
      exact value gnn=11/16. We also determine the connectivity on a free surface as
      gn(surf)=0.6250001(13) and conjecture that this value is exactly equal to 5/8. In
      addition, we find that at criticality, the connectivities depend on the linear
      finite size L as ~L(yt-d), and the associated specific-heat-like quantities Cn
      and Cnn scale as ~L(2yt-d)ln(L/L0), where d is the lattice dimensionality,
      yt=1/nu the thermal renormalization exponent, and L0 a nonuniversal constant. We
      provide an explanation of this logarithmic factor within the theoretical
      framework reported recently by Vasseur et al. [J. Stat. Mech. (2012) L07001].

PMID- 25375438
TI  - Possibility of adiabatic transport of a Majorana edge state through an extended
      gapless region.
AB  - In the context of slow quenching dynamics of a p-wave superconducting chain, it
      has been shown that a Majorana edge state cannot be adiabatically transported
      from one topological phase to the other separated by a quantum critical line. On
      the other hand, the inclusion of a phase factor in the hopping term, which breaks
      the effective time-reversal invariance, results in an extended gapless region
      between two topological phases. We show that for a finite chain with an open
      boundary condition, there exists a nonzero probability that a Majorana edge state
      can be adiabatically transported from one topological phase to the other across
      this gapless region following a slow quench of the superconducting term; this
      happens for an optimum transit time, which is proportional to the system size and
      diverges for a thermodynamically large chain. We attribute this phenomenon to the
      mixing of the Majorana only with low-lying inverted bulk states. Remarkably, the
      Majorana state always persists with the same probability even after the quenching
      is stopped. For a periodic chain, on the other hand, we find a Kibble-Zurek
      scaling of the defect density with a renormalized rate of quenching. 

PMID- 25375439
TI  - Simulating non-Markovian stochastic processes.
AB  - We present a simple and general framework to simulate statistically correct
      realizations of a system of non-Markovian discrete stochastic processes. We give
      the exact analytical solution and a practical and efficient algorithm like the
      Gillespie algorithm for Markovian processes, with the difference being that now
      the occurrence rates of the events depend on the time elapsed since the event
      last took place. We use our non-Markovian generalized Gillespie stochastic
      simulation methodology to investigate the effects of nonexponential interevent
      time distributions in the susceptible-infected-susceptible model of epidemic
      spreading. Strikingly, our results unveil the drastic effects that very subtle
      differences in the modeling of non-Markovian processes have on the global
      behavior of complex systems, with important implications for their understanding
      and prediction. We also assess our generalized Gillespie algorithm on a system of
      biochemical reactions with time delays. As compared to other existing methods, we
      find that the generalized Gillespie algorithm is the most general because it can
      be implemented very easily in cases (such as for delays coupled to the evolution
      of the system) in which other algorithms do not work or need adapted versions
      that are less efficient in computational terms. 

PMID- 25375440
TI  - Spectral domain of large nonsymmetric correlated Wishart matrices.
AB  - We study complex eigenvalues of the Wishart model for nonsymmetric correlation
      matrices. The model is defined for two statistically equivalent but different
      Gaussian real matrices, as C=AB(t)/T, where B(t) is the transpose of B and both
      matrices A and B are of dimensions N*T. If A and B are uncorrelated, or
      equivalently if C vanishes on average, it is known that at large matrix dimension
      the domain of the eigenvalues of C is a circle centered-at-origin and the
      eigenvalue density depends only on the radial distances. We consider actual
      correlation in A and B and derive a result for the contour describing the domain
      of the bulk of the eigenvalues of C in the limit of large N and T where the ratio
      N/T is finite. In particular, we show that the eigenvalue domain is sensitive to
      the correlations. For example, when C is diagonal on average with the same
      element c?0, the contour is no longer a circle centered at origin but a shifted
      ellipse. In this case we explicitly derive a result for the spectral density
      which again depends only on the radial distances. For more general cases, we show
      that the contour depends on the symmetric and antisymmetric parts of the
      correlation matrix resulting from the ensemble-averaged C. If the correlation
      matrix is normal, then the contour depends only on its spectrum. We also provide
      numerics to justify our analytics.

PMID- 25375441
TI  - Nonequilibrium equalities in absolutely irreversible processes.
AB  - We generalize nonequilibrium integral equalities to situations involving
      absolutely irreversible processes for which the forward-path probability vanishes
      and the entropy production diverges, rendering conventional integral fluctuation
      theorems inapplicable. We identify the mathematical origins of absolute
      irreversibility as the singularity of probability measure. We demonstrate the
      validity of the obtained equalities for several models. 

PMID- 25375442
TI  - Anomalous mean-field behavior of the fully connected Ising model.
AB  - Although the fully connected Ising model does not have a length scale, we show
      that the critical exponents for thermodynamic quantities such as the mean
      magnetization and the susceptibility can be obtained using finite size scaling
      with the scaling variable equal to N, the number of spins. Surprisingly, the mean
      value and the most probable value of the magnetization are found to scale
      differently with N at the critical temperature of the infinite system, and the
      magnetization probability distribution is not a Gaussian, even for large N.
      Similar results inconsistent with the usual understanding of mean-field theory
      are found at the spinodal. We relate these results to the breakdown of
      hyperscaling and show that hyperscaling can be restored by increasing N while
      holding the Ginzburg parameter rather than the temperature fixed, or by doing
      finite size scaling at the pseudocritical temperature where the susceptibility is
      a maximum for a given value of N. We conclude that finite size scaling for the
      fully connected Ising model yields different results depending on how the mean
      field limit is approached. 

PMID- 25375443
TI  - One-dimensional Euclidean matching problem: exact solutions, correlation
      functions, and universality.
AB  - We discuss the equivalence relation between the Euclidean bipartite matching
      problem on the line and on the circumference and the Brownian bridge process on
      the same domains. The equivalence allows us to compute the correlation function
      and the optimal cost of the original combinatorial problem in the thermodynamic
      limit; moreover, we solve also the minimax problem on the line and on the
      circumference. The properties of the average cost and correlation functions are
      discussed. 

PMID- 25375444
TI  - Steepest entropy ascent model for far-nonequilibrium thermodynamics: unified
      implementation of the maximum entropy production principle.
AB  - By suitable reformulations, we cast the mathematical frameworks of several well
      known different approaches to the description of nonequilibrium dynamics into a
      unified formulation valid in all these contexts, which extends to such frameworks
      the concept of steepest entropy ascent (SEA) dynamics introduced by the present
      author in previous works on quantum thermodynamics. Actually, the present
      formulation constitutes a generalization also for the quantum thermodynamics
      framework. The analysis emphasizes that in the SEA modeling principle a key role
      is played by the geometrical metric with respect to which to measure the length
      of a trajectory in state space. In the near-thermodynamic-equilibrium limit, the
      metric tensor is directly related to the Onsager's generalized resistivity
      tensor. Therefore, through the identification of a suitable metric field which
      generalizes the Onsager generalized resistance to the arbitrarily far
      nonequilibrium domain, most of the existing theories of nonequilibrium
      thermodynamics can be cast in such a way that the state exhibits the spontaneous
      tendency to evolve in state space along the path of SEA compatible with the
      conservation constraints and the boundary conditions. The resulting unified
      family of SEA dynamical models is intrinsically and strongly consistent with the
      second law of thermodynamics. The non-negativity of the entropy production is a
      general and readily proved feature of SEA dynamics. In several of the different
      approaches to nonequilibrium description we consider here, the SEA concept has
      not been investigated before. We believe it defines the precise meaning and the
      domain of general validity of the so-called maximum entropy production principle.
      Therefore, it is hoped that the present unifying approach may prove useful in
      providing a fresh basis for effective, thermodynamically consistent, numerical
      models and theoretical treatments of irreversible conservative relaxation towards
      equilibrium from far nonequilibrium states. The mathematical frameworks we
      consider are the following: (A) statistical or information-theoretic models of
      relaxation; (B) small-scale and rarefied gas dynamics (i.e., kinetic models for
      the Boltzmann equation); (C) rational extended thermodynamics, macroscopic
      nonequilibrium thermodynamics, and chemical kinetics; (D) mesoscopic
      nonequilibrium thermodynamics, continuum mechanics with fluctuations; and (E)
      quantum statistical mechanics, quantum thermodynamics, mesoscopic nonequilibrium
      quantum thermodynamics, and intrinsic quantum thermodynamics. 

PMID- 25375445
TI  - Growth and dispersal with inertia: hyperbolic reaction-transport systems.
AB  - We investigate the behavior of five hyperbolic reaction-diffusion equations most
      commonly employed to describe systems of interacting organisms or reacting
      particles where dispersal displays inertia. We first discuss the macroscopic or
      mesoscopic foundation, or lack thereof, of these reaction-transport equations.
      This is followed by an analysis of the temporal evolution of spatially uniform
      states. In particular, we determine the uniform steady states of the reaction
      transport systems and their stability properties. We then address the
      spatiotemporal behavior of pure death processes. We end with a unified treatment
      of the front speed for hyperbolic reaction-diffusion equations with Kolmogorov
      Petrosvskii-Piskunov kinetics. In particular, we obtain an exact expression for
      the front speed of a general class of reaction correlated random walk systems.
      Our results establish that three out of the five hyperbolic reaction-transport
      equations provide physically acceptable models of biological and chemical
      systems. 

PMID- 25375446
TI  - Transport through quasi-one-dimensional wires with correlated disorder.
AB  - We study transport properties of bulk-disordered quasi-one-dimensional (Q1D)
      wires paying main attention to the role of long-range correlations embedded into
      the disorder. First, we show that for stratified disorder for which the disorder
      is the same for all individual chains forming the Q1D wire, the transport
      properties can be analytically described provided the disorder is weak. When the
      disorder in every chain is not the same, however it has the same binary
      correlator, the general theory is absent. Thus, we consider the case when only
      one channel is open and all others are closed. For this situation we suggest a
      semianalytical approach which is quite effective for the description of the total
      transmission coefficient. Our numerical data confirm the validity of this
      approach. 

PMID- 25375447
TI  - Kardar-Parisi-Zhang universality class and the anchored Toom interface.
AB  - We revisit the anchored Toom interface and use Kardar-Parisi-Zhang scaling theory
      to argue that the interface fluctuations are governed by the Airy1 process with
      the role of space and time interchanged. The predictions, which contain no free
      parameter, are numerically well confirmed for space-time statistics in the
      stationary state. In particular, the spatial fluctuations of the interface
      computed numerically agree well with those given by the GOE edge distribution of
      Tracy and Widom [Commun. Math. Phys. 177, 727 (1996)].

PMID- 25375448
TI  - Dealing with correlated choices: how a spin-glass model can help political
      parties select their policies.
AB  - Starting from preferences on N proposed policies obtained via questionnaires from
      a sample of the electorate, an Ising spin-glass model in a field can be
      constructed from which a political party could find the subset of the proposed
      policies which would maximize its appeal, form a coherent choice in the eyes of
      the electorate, and have maximum overlap with the party's existing policies. We
      illustrate the application of the procedure by simulations of a spin glass in a
      random field on scale-free networks. 

PMID- 25375449
TI  - Clustering of branching Brownian motions in confined geometries.
AB  - We study the evolution of a collection of individuals subject to Brownian
      diffusion, reproduction, and disappearance. In particular, we focus on the case
      where the individuals are initially prepared at equilibrium within a confined
      geometry. Such systems are widespread in physics and biology and apply for
      instance to the study of neutron populations in nuclear reactors and the dynamics
      of bacterial colonies, only to name a few. The fluctuations affecting the number
      of individuals in space and time may lead to a strong patchiness, with particles
      clustered together. We show that the analysis of this peculiar behavior can be
      rather easily carried out by resorting to a backward formalism based on the
      Green's function, which allows the key physical observables, namely, the particle
      concentration and the pair correlation function, to be explicitly derived. 

PMID- 25375450
TI  - Maximum work extraction and implementation costs for nonequilibrium Maxwell's
      demons.
AB  - We determine the maximum amount of work extractable in finite time by a demon
      performing continuous measurements on a quadratic Hamiltonian system subjected to
      thermal fluctuations, in terms of the information extracted from the system. The
      maximum work demon is found to apply a high-gain continuous feedback involving a
      Kalman-Bucy estimate of the system state and operates in nonequilibrium. A simple
      and concrete electrical implementation of the feedback protocol is proposed,
      which allows for analytic expressions of the flows of energy, entropy, and
      information inside the demon. This let us show that any implementation of the
      demon must necessarily include an external power source, which we prove both from
      classical thermodynamics arguments and from a version of Landauer's memory
      erasure argument extended to nonequilibrium linear systems. 

PMID- 25375451
TI  - Growing spin model in deterministic and stochastic trees.
AB  - We solve the growing asymmetric Ising model [J. Sienkiewicz, K. Suchecki, and J.
      A. Holyst, Phys. Rev. E 89, 012105 (2014)] in the topologies of deterministic and
      stochastic (random) scale-free trees predicting its nonmonotonous behavior for
      external fields smaller than the coupling constant J. In both cases, we indicate
      that the crossover temperature corresponding to maximal magnetization decays
      approximately as (lnlnN)(-1), where N is the number of nodes in the tree.

PMID- 25375452
TI  - Irreversible dynamics, Onsager-Casimir symmetry, and an application to
      turbulence.
AB  - Irreversible contributions to the dynamics of nonequilibrium systems can be
      formulated in terms of dissipative, or irreversible, brackets. We discuss the
      structure of such irreversible brackets in view of a degeneracy implied by energy
      conservation, where we consider different types of symmetries of the bracket
      corresponding to the Onsager and Casimir symmetries of linear irreversible
      thermodynamics. Slip and turbulence provide important examples of antisymmetric
      irreversible brackets and offer guidance for the more general modeling of
      irreversible dynamics without entropy production. Conversely, turbulence modeling
      could benefit from elucidating thermodynamic structure. The examples suggest
      constructing antisymmetric irreversible brackets in terms of completely
      antisymmetric functions of three indices. Irreversible brackets without well
      defined symmetry properties can arise for rare events, causing big
      configurational changes. 

PMID- 25375453
TI  - Complete spectral scaling of time series: towards a classification of 1/f noise.
AB  - The standard spectral scaling, S(f)~1/f(beta), has been traditionally used as a
      correlation measure characterizing the dynamical behavior of time series. The
      ubiquity of 1/f and 1/f(2) spectra in many processes certainly suggests the
      existence of universal mechanisms, but also gives rise to the suspicion that some
      important features are not included in this scaling. In this paper we argue that
      a complete spectral scaling, including as a main variable the size of the series,
      S(f,T)~T(eta)/f(beta), which is usually considered irrelevant, gives an insight
      into this problem. Using synthetically generated series we show that, in general,
      the scaling exponent beta is too generic, while the exponent associated with the
      size, eta, gives a more specific information. Hence, we propose the use of both
      exponents in a scheme to classify series into different universality classes. In
      this way many of the processes appearing in the literature could be better
      identified, and much of the ambiguity that surrounds the standard spectral
      scaling could be clarified.

PMID- 25375454
TI  - Heterogeneity-induced large deviations in activity and (in some cases) entropy
      production.
AB  - We solve a simple model that supports a dynamic phase transition and show
      conditions for the existence of the transition. Using methods of large deviation
      theory we analytically compute the probability distribution for activity and
      entropy production rates of the trajectories on a large ring with a single
      heterogeneous link. The corresponding joint rate function demonstrates two
      dynamical phases--one localized and the other delocalized, but the marginal rate
      functions do not always exhibit the underlying transition. Symmetries in dynamic
      order parameters influence the observation of a transition, such that
      distributions for certain dynamic order parameters need not reveal an underlying
      dynamical bistability. Solution of our model system furthermore yields the form
      of the effective Markov transition matrices that generate dynamics in which the
      two dynamical phases are at coexistence. We discuss the implications of the
      transition for the response of bacterial cells to antibiotic treatment, arguing
      that even simple models of a cell cycle lacking an explicit bistability in
      configuration space will exhibit a bistability of dynamical phases.

PMID- 25375455
TI  - Phase transition properties of the Bell-Lavis model.
AB  - Using Monte Carlo calculations we analyze the order and the universality class of
      phase transitions into a low-density (honeycomb) phase of a triangular
      antiferromagnetic three-state Bell-Lavis model. The results are obtained in a
      whole interval of chemical potential MU corresponding to the honeycomb phase. Our
      results demonstrate that the phase transitions might be attributed to the three
      state Potts universality class for all MU values except for the edges of the
      honeycomb phase existence. At the honeycomb phase and the low-density gas phase
      boundary the transitions become of the first order. At another, honeycomb-to
      frustrated phase boundary, we observe the approach to the crossover from the
      three-state Potts to the Ising model universality class. We also obtain the
      Schottky anomaly in the specific heat close to this edge. We show that the
      intermediate planar phase, found in a very similar antiferromagnetic triangular
      Blume-Capel model, does not occur in the Bell-Lavis model. 

PMID- 25375456
TI  - Derivation of the Lifshitz-Matsubara sum formula for the Casimir pressure between
      metallic plane mirrors.
AB  - We carefully reexamine the conditions of validity for the consistent derivation
      of the Lifshitz-Matsubara sum formula for the Casimir pressure between metallic
      plane mirrors. We recover the usual expression for the lossy Drude model but not
      for the lossless plasma model. We give an interpretation of this new result in
      terms of the modes associated with the Foucault currents, which play a role in
      the limit of vanishing losses, in contrast to common expectations. 

PMID- 25375457
TI  - Thermodynamic bounds and general properties of optimal efficiency and power in
      linear responses.
AB  - We study the optimal exergy efficiency and power for thermodynamic systems with
      an Onsager-type "current-force" relationship describing the linear response to
      external influences. We derive, in analytic forms, the maximum efficiency and
      optimal efficiency for maximum power for a thermodynamic machine described by a
      N*N symmetric Onsager matrix with arbitrary integer N. The figure of merit is
      expressed in terms of the largest eigenvalue of the "coupling matrix" which is
      solely determined by the Onsager matrix. Some simple but general relationships
      between the power and efficiency at the conditions for (i) maximum efficiency and
      (ii) optimal efficiency for maximum power are obtained. We show how the second
      law of thermodynamics bounds the optimal efficiency and the Onsager matrix and
      relate those bounds together. The maximum power theorem (Jacobi's Law) is
      generalized to all thermodynamic machines with a symmetric Onsager matrix in the
      linear-response regime. We also discuss systems with an asymmetric Onsager matrix
      (such as systems under magnetic field) for a particular situation and we show
      that the reversible limit of efficiency can be reached at finite output power.
      Cooperative effects are found to improve the figure of merit significantly in
      systems with multiply cross-correlated responses. Application to example systems
      demonstrates that the theory is helpful in guiding the search for high
      performance materials and structures in energy researches. 

PMID- 25375458
TI  - Cage effect for the velocity correlation functions of a Brownian particle in
      viscoelastic shear flows.
AB  - The long-time limit behavior of velocity correlation functions (VCFs) for an
      underdamped Brownian particle in an oscillatory viscoelastic shear flow is
      investigated using the generalized Langevin equation with a power-law memory
      kernel. The influence of a fluctuating environment is modeled by an additive
      external fractional Gaussian noise. The exact expressions of the correlation
      functions of the fluctuating components of velocity for the Brownian particle in
      the shear plane have been calculated. Also, the particle's angular momentum is
      found. It is shown that in a certain region of the system parameters an interplay
      of the shear flow, memory effects, and external noise can induce a bounded long
      time behavior of the VCFs, even in the shear flow direction, where in the case of
      internal noise the velocity process is subdiffusive, i.e., unbounded in time.
      Moreover, we find resonant behavior of the VCFs and the angular momentum versus
      the shear oscillation frequency, implying that they can be efficiently excited by
      oscillatory shear. The role of the initial positional distribution of particles
      is also discussed. 

PMID- 25375459
TI  - Analytic solution for heat flow through a general harmonic network.
AB  - We present an analytic expression for the heat current through a general harmonic
      network coupled with Ohmic reservoirs. We use a method that enables us to express
      the stationary state of the network in terms of the eigenvectors and eigenvalues
      of a generalized cubic eigenvalue problem. In this way, we obtain exact formulas
      for the heat current and the local temperature inside the network. Our method
      does not rely on the usual assumptions of weak coupling to the environments or on
      the existence of an infinite cutoff in the environmental spectral densities. We
      use this method to study nonequilibrium processes without the weak coupling and
      Markovian approximations. As a first application of our method, we revisit the
      problem of heat conduction in two- and three-dimensional crystals with binary
      mass disorder. We complement previous results showing that for small systems the
      scaling of the heat current with the system size greatly depends on the strength
      of the interaction between system and reservoirs. This somewhat counterintuitive
      result seems not to have been noticed before. 

PMID- 25375460
TI  - Aftershock production rate of driven viscoelastic interfaces.
AB  - We study analytically and by numerical simulations the statistics of the
      aftershocks generated after large avalanches in models of interface depinning
      that include viscoelastic relaxation effects. We find in all the analyzed cases
      that the decay law of aftershocks with time can be understood by considering the
      typical roughness of the interface and its evolution due to relaxation. In models
      where there is a single viscoelastic relaxation time there is an exponential
      decay of the number of aftershocks with time. In models in which viscoelastic
      relaxation is wave-vector dependent we typically find a power-law dependence of
      the decay rate that is compatible with the Omori law. The factors that determine
      the value of the decay exponent are analyzed. 

PMID- 25375461
TI  - Approach to approximating the pair distribution function of inhomogeneous hard
      sphere fluids.
AB  - We introduce an approximation for the pair distribution function of the
      inhomogeneous hard sphere fluid. Our approximation makes use of our recently
      published averaged pair distribution function at contact, which has been shown to
      accurately reproduce the averaged pair distribution function at contact for
      inhomogeneous density distributions. This approach achieves greater computational
      efficiency than previous approaches by enabling the use of exclusively fixed
      kernel convolutions and thus allowing an implementation using fast Fourier
      transforms. We compare results for our pair distribution approximation with two
      previously published works and Monte Carlo simulation, showing favorable results.

PMID- 25375462
TI  - Deriving fundamental measure theory from the virial series: consistency with the
      zero-dimensional limit.
AB  - Fundamental measure theory (FMT) for hard particles has great potential for
      predicting the phase behavior of colloidal and nanometric shapes. The modern
      versions of FMT are usually derived from the zero-dimensional limit, a system of
      at most one particle confined in a collection of cavities in the limit that all
      cavities shrink to the size of the particle. In Phys. Rev. E 85, 041150 (2012), a
      derivation from an approximated and resummed virial expansion was presented,
      whose result was not fully consistent with the FMT from the zero-dimensional
      limit. Here we improve on this derivation and obtain exactly the same FMT
      functional as was obtained earlier from the zero-dimensional limit. As a result,
      further improvements of FMT based on the virial expansion can now be formulated,
      some of which we suggest in the outlook. 

PMID- 25375463
TI  - Enhanced rare-region effects in the contact process with long-range correlated
      disorder.
AB  - We investigate the nonequilibrium phase transition in the disordered contact
      process in the presence of long-range spatial disorder correlations. These
      correlations greatly increase the probability for finding rare regions that are
      locally in the active phase while the bulk system is still in the inactive phase.
      Specifically, if the correlations decay as a power of the distance, the rare
      region probability is a stretched exponential of the rare-region size rather than
      a simple exponential as is the case for uncorrelated disorder. As a result, the
      Griffiths singularities are enhanced and take a non-power-law form. The critical
      point itself is of infinite-randomness type but with critical exponent values
      that differ from the uncorrelated case. We report large-scale Monte Carlo
      simulations that verify and illustrate our theory. We also discuss
      generalizations to higher dimensions and applications to other systems such as
      the random transverse-field Ising model, itinerant magnets, and the
      superconductor-metal transition. 

PMID- 25375464
TI  - Quantum distance and the Euler number index of the Bloch band in a one
      dimensional spin model.
AB  - We study the Riemannian metric and the Euler characteristic number of the Bloch
      band in a one-dimensional spin model with multisite spins exchange interactions.
      The Euler number of the Bloch band originates from the Gauss-Bonnet theorem on
      the topological characterization of the closed Bloch states manifold in the first
      Brillouin zone. We study this approach analytically in a transverse field XY spin
      chain with three-site spin coupled interactions. We define a class of cyclic
      quantum distance on the Bloch band and on the ground state, respectively, as a
      local characterization for quantum phase transitions. Specifically, we give a
      general formula for the Euler number by means of the Berry curvature in the case
      of two-band models, which reveals its essential relation to the first Chern
      number of the band insulators. Finally, we show that the ferromagnetic
      paramagnetic phase transition in zero temperature can be distinguished by the
      Euler number of the Bloch band. 

PMID- 25375465
TI  - Evolutionary dynamics of the traveler's dilemma and minimum-effort coordination
      games on complex networks.
AB  - The traveler's dilemma game and the minimum-effort coordination game are social
      dilemmas that have received significant attention resulting from the fact that
      the predictions of classical game theory are inconsistent with the results found
      when the games are studied experimentally. Moreover, both the traveler's dilemma
      and the minimum-effort coordination games have potentially important applications
      in evolutionary biology. Interestingly, standard deterministic evolutionary game
      theory, as represented by the replicator dynamics in a well-mixed population, is
      also inadequate to account for the behavior observed in these games. Here we
      study the evolutionary dynamics of both these games in populations with
      interaction patterns described by a variety of complex network topologies. We
      investigate the evolutionary dynamics of these games through agent-based
      simulations on both model and empirical networks. In particular, we study the
      effects of network clustering and assortativity on the evolutionary dynamics of
      both games. In general, we show that the evolutionary behavior of the traveler's
      dilemma and minimum-effort coordination games on complex networks is in good
      agreement with that observed experimentally. Thus, formulating the traveler's
      dilemma and the minimum-effort coordination games on complex networks neatly
      resolves the paradoxical aspects of these games. 

PMID- 25375466
TI  - Exact dynamics of stochastic linear delayed systems: application to
      spatiotemporal coordination of comoving agents.
AB  - Delayed dynamics result from finite transmission speeds of a signal in the form
      of energy, mass, or information. In stochastic systems the resulting lagged
      dynamics challenge our understanding due to the rich behavioral repertoire
      encompassing monotonic, oscillatory, and unstable evolution. Despite the vast
      literature, quantifying this rich behavior is limited by a lack of explicit
      analytic studies of high-dimensional stochastic delay systems. Here we fill this
      gap for systems governed by a linear Langevin equation of any number of delays
      and spatial dimensions with additive Gaussian noise. By exploiting Laplace
      transforms we are able to derive an exact time-dependent analytic solution of the
      Langevin equation. By using characteristic functionals we are able to construct
      the full time dependence of the multivariate probability distribution of the
      stochastic process as a function of the delayed and nondelayed random variables.
      As an application we consider interactions in animal collective movement that go
      beyond the traditional assumption of instantaneous alignment. We propose models
      for coordinated maneuvers of comoving agents applicable to recent empirical
      findings in pigeons and bats whereby individuals copy the heading of their
      neighbors with some delay. We highlight possible strategies that individual pairs
      may adopt to reduce the variance in their velocity difference and/or in their
      spatial separation. We also show that a minimum in the variance of the spatial
      separation at long times can be achieved with certain ratios of measurement to
      reaction delay. 

PMID- 25375467
TI  - Solvable random-walk model with memory and its relations with Markovian models of
      anomalous diffusion.
AB  - Motivated by studies on the recurrent properties of animal and human mobility, we
      introduce a path-dependent random-walk model with long-range memory for which not
      only the mean-square displacement (MSD) but also the propagator can be obtained
      exactly in the asymptotic limit. The model consists of a random walker on a
      lattice, which, at a constant rate, stochastically relocates at a site occupied
      at some earlier time. This time in the past is chosen randomly according to a
      memory kernel, whose temporal decay can be varied via an exponent parameter. In
      the weakly non-Markovian regime, memory reduces the diffusion coefficient from
      the bare value. When the mean backward jump in time diverges, the diffusion
      coefficient vanishes and a transition to an anomalous subdiffusive regime occurs.
      Paradoxically, at the transition, the process is an anticorrelated Levy flight.
      Although in the subdiffusive regime the model exhibits some features of the
      continuous time random walk with infinite mean waiting time, it belongs to
      another universality class. If memory is very long-ranged, a second transition
      takes place to a regime characterized by a logarithmic growth of the MSD with
      time. In this case the process is asymptotically Gaussian and effectively
      described as a scaled Brownian motion with a diffusion coefficient decaying as
      1/t. 

PMID- 25375468
TI  - Markov-random-field modeling for linear seismic tomography.
AB  - We apply the Markov-random-field model to linear seismic tomography and propose a
      method to estimate the hyperparameters for the smoothness and the magnitude of
      the noise. Optimal hyperparameters can be determined analytically by minimizing
      the free energy function, which is defined by marginalizing the evaluation
      function. In synthetic inversion tests under various settings, the assumed
      velocity structures are successfully reconstructed, which shows the effectiveness
      and robustness of the proposed method. The proposed mathematical framework can be
      applied to inversion problems in various fields in the natural sciences. 

PMID- 25375469
TI  - Two-dimensional nonlinear map characterized by tunable Levy flights.
AB  - After recognizing that point particles moving inside the extended version of the
      rippled billiard perform Levy flights characterized by a Levy-type distribution
      P(l)~l(-(1+alpha)) with alpha=1, we derive a generalized two-dimensional
      nonlinear map Malpha able to produce Levy flights described by P(l) with
      0<alpha<2. Due to this property, we call Malpha the Levy map. Then, by applying
      Chirikov's overlapping resonance criteria, we are able to identify the onset of
      global chaos as a function of the parameters of the map. With this, we state the
      conditions under which the Levy map could be used as a Levy pseudorandom number
      generator and furthermore confirm its applicability by computing scattering
      properties of disordered wires.

PMID- 25375470
TI  - Quantum phase transitions of atom-molecule Bose mixtures in a double-well
      potential.
AB  - The ground state and spectral properties of Bose gases in double-well potentials
      are studied in two different scenarios: (i) an interacting atomic Bose gas, and
      (ii) a mixture of an atomic gas interacting with diatomic molecules. A ground
      state second-order quantum phase transition is observed in both scenarios. For
      large attractive values of the atom-atom interaction, the ground state is
      degenerate. For repulsive and small attractive interaction, the ground state is
      not degenerate and is well approximated by a boson coherent state. Both systems
      depict an excited state quantum phase transition. In both cases, a critical
      energy separates a region in which all the energy levels are degenerate in pairs,
      from another region in which there are no degeneracies. For the atomic system,
      the critical point displays a singularity in the density of states, whereas this
      behavior is largely smoothed for the mixed atom-molecule system. 

PMID- 25375471
TI  - Dynamics and quantumness of excitation energy transfer through a complex quantum
      network.
AB  - Understanding the mechanisms of efficient and robust energy transfer in organic
      systems provides us with insights for the optimal design of artificial systems.
      In this paper, we explore the dynamics of excitation energy transfer (EET)
      through a complex quantum network by a toy model consisting of three sites
      coupled to environments. We study how the coherent evolution and the noise
      induced decoherence work together to reach efficient EET and illustrate the role
      of the phase factor attached to the coupling constant in the EET. By comparing
      the differences between the Markovian and non-Markovian dynamics, we discuss the
      effect of environment and the spatial structure of system on the dynamics and the
      efficiency of EET. A intuitive picture is given to show how the exciton is
      transferred through the system. Employing the simple model, we show the
      robustness of EET efficiency under the influence of the environment and elucidate
      the important role of quantum coherence in EET. We go further to study the
      quantum feature of the EET dynamics by quantumness and show the importance of
      quantum coherence from a different perspective. We calculate the energy current
      in the EET and its quantumness, and results for different system parameters are
      presented and discussed. 

PMID- 25375472
TI  - Quantum phase transitions in networks of Lipkin-Meshkov-Glick models.
AB  - We study the quantum critical behavior of networks consisting of Lipkin-Meshkov
      Glick models with an anisotropic ferromagnetic coupling. We focus on the low
      energy properties of the system within a mean-field approach and the quantum
      corrections around the mean-field solution. Our results show that the weak
      coupling regime corresponds to the paramagnetic phase when the local field
      dominates the dynamics, but the local anisotropy leads to the existence of an
      exponentially degenerate ground state. In the strong-coupling regime, the ground
      state is twofold degenerate and possesses long-range magnetic ordering.
      Analytical results for a network with the ring topology are obtained. 

PMID- 25375473
TI  - Flux rectification in the quantum XXZ chain.
AB  - Thermal rectification is the phenomenon by which the flux of heat depends on the
      direction of the flow. It has attracted much interest in recent years due to the
      possibility of devising thermal diodes. In this paper, we consider the
      rectification phenomenon in the quantum XXZ chain subject to an inhomogeneous
      field. The chain is driven out of equilibrium by the contact at its boundaries
      with two different reservoirs, leading to a constant flow of magnetization from
      one bath to the other. The nonunitary dynamics of this system, which is modeled
      by a Lindblad master equation, is treated exactly for small sizes and numerically
      for larger ones. The functional dependence of the rectification coefficient on
      the model parameters (anisotropy, field amplitude, and out of equilibrium driving
      strength) is investigated in full detail. Close to the XX point and at small
      inhomogeneity and low driving, we have found an explicit expression for the
      rectification coefficient that is valid at all system sizes. In particular, it
      shows that the phenomenon of rectification persists even in the thermodynamic
      limit. Finally, we prove that in the case of the XX chain, there is no
      rectification. 

PMID- 25375474
TI  - Phenomenological picture of fluctuations in branching random walks.
AB  - We propose a picture of the fluctuations in branching random walks, which leads
      to predictions for the distribution of a random variable that characterizes the
      position of the bulk of the particles. We also interpret the 1/sqrt[t] correction
      to the average position of the rightmost particle of a branching random walk for
      large times t?1, computed by Ebert and Van Saarloos, as fluctuations on top of
      the mean-field approximation of this process with a Brunet-Derrida cutoff at the
      tip that simulates discreteness. Our analytical formulas successfully compare to
      numerical simulations of a particular model of a branching random walk. 

PMID- 25375475
TI  - Spectral density of the noncentral correlated Wishart ensembles.
AB  - Wishart ensembles of random matrix theory have been useful in modeling positive
      definite matrices encountered in classical and quantum chaotic systems. We
      consider nonzero means for the entries of the constituting matrix A which defines
      the correlated Wishart matrix as W=AA(?), and refer to the ensemble of such
      Wishart matrices as the noncentral correlated Wishart ensemble (nc-CWE). We
      derive the Pastur self-consistent equation which describes the spectral density
      of nc-CWE at large matrix dimension.

PMID- 25375476
TI  - Geometric critical exponents in classical and quantum phase transitions.
AB  - We define geometric critical exponents for systems that undergo continuous second
      order classical and quantum phase transitions. These relate scalar quantities on
      the information theoretic parameter manifolds of such systems, near criticality.
      We calculate these exponents by approximating the metric and thereby solving
      geodesic equations analytically, near curvature singularities of two-dimensional
      parameter manifolds. The critical exponents are seen to be the same for both
      classical and quantum systems that we consider, and we provide evidence about the
      possible universality of our results. 

PMID- 25375477
TI  - Single-particle stochastic heat engine.
AB  - We have performed an extensive analysis of a single-particle stochastic heat
      engine constructed by manipulating a Brownian particle in a time-dependent
      harmonic potential. The cycle consists of two isothermal steps at different
      temperatures and two adiabatic steps similar to that of a Carnot engine. The
      engine shows qualitative differences in inertial and overdamped regimes. All the
      thermodynamic quantities, including efficiency, exhibit strong fluctuations in a
      time periodic steady state. The fluctuations of stochastic efficiency dominate
      over the mean values even in the quasistatic regime. Interestingly, our system
      acts as an engine provided the temperature difference between the two reservoirs
      is greater than a finite critical value which in turn depends on the cycle time
      and other system parameters. This is supported by our analytical results carried
      out in the quasistatic regime. Our system works more reliably as an engine for
      large cycle times. By studying various model systems, we observe that the
      operational characteristics are model dependent. Our results clearly rule out any
      universal relation between efficiency at maximum power and temperature of the
      baths. We have also verified fluctuation relations for heat engines in time
      periodic steady state. 

PMID- 25375478
TI  - Out-of-equilibrium evolution of kinetically constrained many-body quantum systems
      under purely dissipative dynamics.
AB  - We explore the relaxation dynamics of quantum many-body systems that undergo
      purely dissipative dynamics through non-classical jump operators that can
      establish quantum coherence. Our goal is to shed light on the differences in the
      relaxation dynamics that arise in comparison to systems evolving via classical
      rate equations. In particular, we focus on a scenario where both quantum and
      classical dissipative evolution lead to a stationary state with the same values
      of diagonal or "classical" observables. As a basis for illustrating our ideas we
      use spin systems whose dynamics becomes correlated and complex due to dynamical
      constraints, inspired by kinetically constrained models (KCMs) of classical
      glasses. We show that in the quantum case the relaxation can be orders of
      magnitude slower than the classical one due to the presence of quantum
      coherences. Aspects of these idealized quantum KCMs become manifest in a strongly
      interacting Rydberg gas under electromagnetically induced transparency (EIT)
      conditions in an appropriate limit. Beyond revealing a link between this Rydberg
      gas and the rather abstract dissipative KCMs of quantum glassy systems, our study
      sheds light on the limitations of the use of classical rate equations for
      capturing the non-equilibrium behavior of this many-body system. 

PMID- 25375479
TI  - Usage leading to an abrupt collapse of connectivity.
AB  - Network infrastructures are essential for the distribution of resources such as
      electricity and water. Typical strategies to assess their resilience focus on the
      impact of a sequence of random or targeted failures of network nodes or links.
      Here we consider a more realistic scenario, where elements fail based on their
      usage. We propose a dynamic model of transport based on the Bak-Tang-Wiesenfeld
      sandpile model where links fail after they have transported more than an amount
      MU (threshold) of the resource and we investigate it on the square lattice. As we
      deal with a new model, we provide insight on its fundamental behavior and
      dependence on parameters. We observe that, for low values of the threshold due to
      a positive feedback of link failure, an avalanche develops that leads to an
      abrupt collapse of the lattice. By contrast, for high thresholds the lattice
      breaks down in an uncorrelated fashion. We determine the critical threshold MU*
      separating these two regimes and show how it depends on the toppling threshold of
      the nodes and the mass increment added stepwise to the system. We find that the
      time of major disconnection is well described with a linear dependence on MU.
      Furthermore, we propose a lower bound for MU* by measuring the strength of the
      dynamics leading to abrupt collapses.

PMID- 25375480
TI  - Two-strain competition in quasineutral stochastic disease dynamics.
AB  - We develop a perturbation method for studying quasineutral competition in a broad
      class of stochastic competition models and apply it to the analysis of fixation
      of competing strains in two epidemic models. The first model is a two-strain
      generalization of the stochastic susceptible-infected-susceptible (SIS) model.
      Here we extend previous results due to Parsons and Quince [Theor. Popul. Biol.
      72, 468 (2007)], Parsons et al. [Theor. Popul. Biol. 74, 302 (2008)], and Lin,
      Kim, and Doering [J. Stat. Phys. 148, 646 (2012)]. The second model, a two-strain
      generalization of the stochastic susceptible-infected-recovered (SIR) model with
      population turnover, has not been studied previously. In each of the two models,
      when the basic reproduction numbers of the two strains are identical, a system
      with an infinite population size approaches a point on the deterministic
      coexistence line (CL): a straight line of fixed points in the phase space of
      subpopulation sizes. Shot noise drives one of the strain populations to fixation,
      and the other to extinction, on a time scale proportional to the total population
      size. Our perturbation method explicitly tracks the dynamics of the probability
      distribution of the subpopulations in the vicinity of the CL. We argue that,
      whereas the slow strain has a competitive advantage for mathematically "typical"
      initial conditions, it is the fast strain that is more likely to win in the
      important situation when a few infectives of both strains are introduced into a
      susceptible population. 

PMID- 25375481
TI  - Stochastic thermodynamics with information reservoirs.
AB  - We generalize stochastic thermodynamics to include information reservoirs. Such
      information reservoirs, which can be modeled as a sequence of bits, modify the
      second law. For example, work extraction from a system in contact with a single
      heat bath becomes possible if the system also interacts with an information
      reservoir. We obtain an inequality, and the corresponding fluctuation theorem,
      generalizing the standard entropy production of stochastic thermodynamics. From
      this inequality we can derive an information processing entropy production, which
      gives the second law in the presence of information reservoirs. We also develop a
      systematic linear response theory for information processing machines. For a
      unicyclic machine powered by an information reservoir, the efficiency at maximum
      power can deviate from the standard value of 1/2. For the case where energy is
      consumed to erase the tape, the efficiency at maximum erasure rate is found to be
      1/2. 

PMID- 25375482
TI  - Cattaneo-type subdiffusion-reaction equation.
AB  - Subdiffusion in a system in which mobile particles A can chemically react with
      static particles B according to the rule A+B->B is considered within a persistent
      random-walk model. This model, which assumes a correlation between successive
      steps of particles, provides hyperbolic Cattaneo normal diffusion or fractional
      subdiffusion equations. Starting with the difference equation, which describes a
      persistent random walk in a system with chemical reactions, using the generating
      function method and the continuous-time random-walk formalism, we will derive the
      Cattaneo-type subdiffusion differential equation with fractional time derivatives
      in which the chemical reactions mentioned above are taken into account. We will
      also find its solution over a long time limit. Based on the obtained results, we
      will find the Cattaneo-type subdiffusion-reaction equation in the case in which
      mobile particles of species A and B can chemically react according to a more
      complicated rule. 

PMID- 25375483
TI  - Extreme power law in a driven many-particle system without threshold dynamics.
AB  - We study a one-dimensional system of spatially extended particles, which are
      attached to regularly spaced locations by means of elastic springs. The particles
      are assumed to be driven by Gaussian noise and to have dissipative, energy
      conserving, or antidissipative (pinball-like) interactions, when the particle
      density exceeds a critical threshold. While each particle in separation shows a
      well-behaved behavior characterized by a Gaussian velocity distribution, the
      interaction of particles at high densities can cause an avalanchelike momentum
      and energy transfer, which can generate extreme (steep) power laws without a well
      defined variance and mean value. Specifically, the velocity variance increases
      dramatically towards the free boundaries of the driven many-particle system. The
      model might also have some relevance for better understanding of crowd disasters.
      Our results suggest that these are most likely caused by passive momentum
      transfers, not by active pushing. 

PMID- 25375484
TI  - Avalanche contribution to shear modulus of granular materials.
AB  - Shear modulus of frictionless granular materials near the jamming transition
      under oscillatory shear is numerically investigated. It is found that the shear
      modulus G satisfies a scaling law to interpolate between G~(phi-phiJ)(1/2) and
      G~gamma0(-1/2)(phi-phiJ) for a linear spring model of the elastic interaction
      between contacting grains, where phi, phiJ, and gamma0 are, respectively, the
      volume fraction of grains, the fraction at the jamming point, and the amplitude
      of the oscillatory shear. The linear relation between the shear modulus and phi
      phiJ can be understood by slip avalanches.

PMID- 25375485
TI  - Force chains in monodisperse spherical particle assemblies: three-dimensional
      measurements using neutrons.
AB  - The full triaxial stress state within individual particles in a monodisperse
      spherical granular assembly has been measured. This was made possible by neutron
      imaging and computed tomography combined with neutron diffraction strain
      measurement techniques and associated stress reconstruction. The assembly in
      question consists of 549 precision steel ball bearings under an applied axial
      load of 85 MPa in a cylindrical die. Clear evidence of force chains was observed
      in terms of both the shape of the probability distribution function for normal
      stresses and the network formed by highly loaded particles. An extensive analysis
      of the source and magnitude of uncertainty in these measurements is also
      presented. 

PMID- 25375486
TI  - Wave tailoring by precompression in confined granular systems.
AB  - We present a granular system whose response under an impact load can be varied
      from rapidly decaying to almost constant amplitude waves by an external
      regulator. The system consists of a granular chain of larger spheres surrounded
      by small spheres, confined in a hollow cylindrical tube and supporting wave
      propagation along the axis of the cylinder. We demonstrate using numerical
      simulations that the response can be controlled by applying radial
      precompression. These observations are then complemented by an asymptotic
      analysis, which shows that the decay in the leading wave is due to energy leakage
      to the oscillating small beads in the tail of the wave. This system has potential
      applications in systems requiring tuning of elastic waves. 

PMID- 25375487
TI  - Kinetics of gravity-driven water channels under steady rainfall.
AB  - We investigate the formation of fingered flow in dry granular media under
      simulated rainfall using a quasi-two-dimensional experimental setup composed of a
      random close packing of monodisperse glass beads. Using controlled experiments,
      we analyze the finger instabilities that develop from the wetting front as a
      function of fundamental granular (particle size) and fluid properties (rainfall,
      viscosity). These finger instabilities act as precursors for water channels,
      which serve as outlets for water drainage. We look into the characteristics of
      the homogeneous wetting front and channel size as well as estimate relevant time
      scales involved in the instability formation and the velocity of the channel
      fingertip. We compare our experimental results with that of the well-known
      prediction developed by Parlange and Hill [D. E. Hill and J. Y. Parlange, Soil
      Sci. Soc. Am. Proc. 36, 697 (1972)]. This model is based on linear stability
      analysis of the growth of perturbations arising at the interface between two
      immiscible fluids. Results show that, in terms of morphology, experiments agree
      with the proposed model. However, in terms of kinetics we nevertheless account
      for another term that describes the homogenization of the wetting front. This
      result shows that the manner we introduce the fluid to a porous medium can also
      influence the formation of finger instabilities. The results also help us to
      calculate the ideal flow rate needed for homogeneous distribution of water in the
      soil and minimization of runoff, given the grain size, fluid density, and fluid
      viscosity. This could have applications in optimizing use of irrigation water. 

PMID- 25375488
TI  - Collective excitations in soft-sphere fluids.
AB  - Despite that the thermodynamic distinction between a liquid and the corresponding
      gas ceases to exist at the critical point, it has been recently shown that
      reminiscence of gaslike and liquidlike behavior can be identified in the
      supercritical fluid region, encoded in the behavior of hypersonic waves
      dispersion. By using a combination of molecular dynamics simulations and
      calculations within the approach of generalized collective modes, we provide an
      accurate determination of the dispersion of longitudinal and transverse
      collective excitations in soft-sphere fluids. Specifically, we address the
      decreasing rigidity upon density reduction along an isothermal line, showing that
      the positive sound dispersion, an excess of sound velocity over the hydrodynamic
      limit typical for dense liquids, displays a nonmonotonic density dependence
      strictly correlated to that of thermal diffusivity and kinematic viscosity. This
      allows rationalizing recent observation parting the supercritical state based on
      the Widom line, i.e., the extension of the coexistence line. Remarkably, we show
      here that the extremals of transport properties such as thermal diffusivity and
      kinematic viscosity provide a robust definition for the boundary between
      liquidlike and gaslike regions, even in those systems without a liquid-gas
      binodal line. Finally, we discuss these findings in comparison with recent
      results for Lennard-Jones model fluid and with the notion of the "rigid-nonrigid"
      fluid separation lines. 

PMID- 25375489
TI  - Collective excitations of hydrodynamically coupled driven colloidal particles.
AB  - Two colloidal particles, driven around an optical vortex trap, have been recently
      shown to pair due to an interplay between hydrodynamic interactions and the
      curved path they are forced to follow. We demonstrate here that this pairing
      interaction can be tuned experimentally, and we study its effect on the
      collective excitations of many particles driven around such an optical trap. We
      find that even though the system is overdamped, hydrodynamic interactions due to
      driving give rise to nondecaying excitations with characteristic dispersion
      relations. The collective excitations of the colloidal ring reflect fluctuations
      of particle pairs rather than those of single particles. 

PMID- 25375490
TI  - Evolution of atomic rearrangements in deformation in metallic glasses.
AB  - Atomic rearrangements induced by shear stress are fundamental for understanding
      deformation mechanisms in metallic glasses (MGs). Using molecular dynamic
      simulation, the atomic rearrangements characterized by nonaffine displacements
      (NADs) and their spatial distribution and evolution with tensile stress in
      Cu50Zr50 MG were investigated. It was found that in the elastic regime the atomic
      rearrangements with the largest NADs are relatively homogeneous in space, but
      exhibit strong spatial correlation, become localized and inhomogeneous, and form
      large clusters as strain increases, which may facilitate the so-called shear
      transformation zones. Furthermore, initially they prefer to take place around Cu
      atoms which have more nonicosahedral configurations. As strain increases, the
      preference decays and disappears in the plastic regime. The atomic rearrangements
      with the smallest NADs are preferentially located around Cu atoms, too, but with
      more icosahedral or icosahedral-like atomic configurations. The preference is
      maintained in the whole deformation process. In contrast, the atomic
      rearrangements with moderate NADs distribute homogeneously, and do not show
      explicit preference or spatial correlation, acting as matrix during deformation.
      Among the atomic rearrangements with different NADs, those with largest and
      smallest NADs are nearest neighbors initially, but separating with increasing
      strain, while those with largest and moderate NADs always avoid to each other.
      The correlations in the fluctuations of the NADs confirm the long-range strain
      correlation and the scale-free characteristic of NADs in both elastic and plastic
      deformation, which suggests a universality of the scaling in the plastic flow in
      MGs.

PMID- 25375492
TI  - Local shear transformations in deformed and quiescent hard-sphere colloidal
      glasses.
AB  - We perform a series of deformation experiments on a monodisperse, hard-sphere
      colloidal glass while simultaneously following the three-dimensional trajectories
      of roughly 50,000 individual particles with a confocal microscope. In each
      experiment, we deform the glass in pure shear at a constant strain rate [(1
      5)*10(-5) s(-1)] to maximum macroscopic strains (5%-10%) and then reverse the
      deformation at the same rate to return to zero macroscopic strain. We also
      measure three-dimensional particle trajectories in an identically prepared
      quiescent glass in which the macroscopic strain is always zero. We find that
      shear transformation zones exist and are active in both sheared and quiescent
      colloidal glasses, revealed by a distinctive fourfold signature in spatial
      autocorrelations of the local shear strain. With increasing shear, the population
      of local shear transformations develops more quickly than in a quiescent glass
      and many of these transformations are irreversible. When the macroscopic strain
      is reversed, we observe partial elastic recovery, followed by plastic deformation
      of the opposite sign, required to compensate for the irreversibly transformed
      regions. The average diameter of the shear transformation zones in both strained
      and quiescent glasses is slightly more than two particle diameters.

PMID- 25375491
TI  - Phase separation and emergent structures in an active nematic fluid.
AB  - We consider a phenomenological continuum theory for an active nematic fluid and
      show that there exists a universal, model-independent instability which renders
      the homogeneous nematic state unstable to order fluctuations. Using numerical and
      analytic tools we show that, in the vicinity of a critical point, this
      instability leads to a phase-separated state in which the ordered regions form
      bands in which the direction of nematic order is perpendicular to the direction
      of the density gradient. We argue that the underlying mechanism that leads to
      this phase separation is a universal feature of active fluids of different
      symmetries. 

PMID- 25375493
TI  - Cluster phases of penetrable rods on a line.
AB  - Phase transitions are uncommon among homogeneous one-dimensional fluids of
      classical particles owing to a general nonexistence result due to van Hove. A way
      to circumvent van Hove's theorem is to consider an interparticle potential that
      is finite everywhere. Of this type is the generalized exponential model of index
      4 (GEM4 potential), a model interaction which in three dimensions provides an
      accurate description of the effective pair repulsion between dissolved soft
      macromolecules (e.g., flexible dendrimers). Using specialized free-energy
      methods, I reconstruct the equilibrium phase diagram of the one-dimensional GEM4
      system, showing that, apart from the usual fluid phase at low densities, it
      consists of an endless sequence of cluster fluid phases of increasing pressure,
      having a sharp crystal appearance for low temperatures. The coexistence line
      between successive phases in the sequence invariably terminates at a critical
      point. Focussing on the first of such transitions, I show that the growth of the
      two-cluster phase from the metastable ordinary fluid is extremely slow, even for
      large supersaturations. Finally, I clarify the apparent paradox of the
      observation of an activation barrier to nucleation in a system where, due to the
      dimensionality of the hosting space, the critical radius is expected to vanish. 

PMID- 25375494
TI  - Domain and droplet sizes in emulsions stabilized by colloidal particles.
AB  - Particle-stabilized emulsions are commonly used in various industrial
      applications. These emulsions can present in different forms, such as Pickering
      emulsions or bijels, which can be distinguished by their different topologies and
      rheology. We numerically investigate the effect of the volume fraction and the
      uniform wettability of the stabilizing spherical particles in mixtures of two
      fluids. For this, we use the well-established three-dimensional lattice Boltzmann
      method, extended to allow for the added colloidal particles with non-neutral
      wetting properties. We obtain data on the domain sizes in the emulsions by using
      both structure functions and the Hoshen-Kopelman (HK) algorithm, and we
      demonstrate that both methods have their own (dis)advantages. We confirm an
      inverse dependence between the concentration of particles and the average radius
      of the stabilized droplets. Furthermore, we demonstrate the effect of particles
      detaching from interfaces on the emulsion properties and domain-size
      measurements. 

PMID- 25375495
TI  - Segregation and phase inversion of strongly and weakly fluctuating Brownian
      particle mixtures and a chain of such particle mixtures in spherical containers.
AB  - We investigate the segregation pattern formation of strongly and weakly
      fluctuating Brownian particle mixtures confined in a three-dimensional spherical
      container. We consider systems where the particle motion is restricted by the
      harmonic external trapping potential and the container edge wall. In such
      systems, two segregation patterns are observed. When the container radius is
      sufficiently large, more weakly fluctuating particles accumulate near the center
      of the container than strongly fluctuating particles. On the other hand, the
      distributions of the strongly and weakly fluctuating particles are inverted when
      the container radius is small. With no external trapping potentials, we find
      similar segregation and phase inversion if the particles construct a chain
      (heterofluctuating polymer) and are confined in a three-dimensional spherical
      container. We could apply these phenomena in the study of biopolymer behavior,
      such as chromosomes in the cell nucleus. 

PMID- 25375496
TI  - Long-term influence of fluid inertia on the diffusion of a Brownian particle.
AB  - We experimentally measure the effects of fluid inertia on the diffusion of a
      Brownian particle at very long time scales. In previous experiments, the use of
      standard optical tweezers introduced a cutoff in the free diffusion of the
      particle, which limited the measurement of these effects to times comparable with
      the relaxation time of the fluid inertia, i.e., a few milliseconds. Here, by
      using blinking optical tweezers, we detect these inertial effects on time scales
      several orders longer up to a few seconds. The measured mean square displacement
      of a freely diffusing Brownian particle in a liquid shows a deviation from the
      Einstein-Smoluchowsky theory that diverges with time. These results are
      consistent with a generalized theory that takes into account not only the
      particle inertia but also the inertia of the surrounding fluid. 

PMID- 25375497
TI  - Variation of the dynamic susceptibility along an isochrone.
AB  - Koperwas et al. showed in a recent paper [Phys. Rev. Lett. 111, 125701 (2013)]
      that the dynamic susceptibility chi4 as estimated by dielectric measurements for
      certain glass-forming liquids decreases substantially with increasing pressure
      along a curve of constant relaxation time. This observation is at odds with other
      measures of dynamics being invariant and seems to pose a problem for theories of
      glass formation. We show that this variation is in fact consistent with
      predictions for liquids with hidden scale invariance: Measures of dynamics at
      constant volume are invariant along isochrones, called isomorphs in such liquids,
      but contributions to fluctuations from long-wavelength fluctuations can vary.
      This is related to the known noninvariance of the isothermal bulk modulus.
      Considering the version of chi4 defined for the NVT ensemble, data from
      simulations of a binary Lennard-Jones liquid show in fact a slight increase with
      increasing density. This is a true departure from the formal invariance expected
      for this quantity.

PMID- 25375498
TI  - Tunable dynamic response of magnetic gels: impact of structural properties and
      magnetic fields.
AB  - Ferrogels and magnetic elastomers feature mechanical properties that can be
      reversibly tuned from outside through magnetic fields. Here we concentrate on the
      question of how their dynamic response can be adjusted. The influence of three
      factors on the dynamic behavior is demonstrated using appropriate minimal models:
      first, the orientational memory imprinted into one class of the materials during
      their synthesis; second, the structural arrangement of the magnetic particles in
      the materials; and third, the strength of an external magnetic field. To
      illustrate the latter point, structural data are extracted from a real
      experimental sample and analyzed. Understanding how internal structural
      properties and external influences impact the dominant dynamical properties helps
      to design materials that optimize the requested behavior. 

PMID- 25375499
TI  - Probing cooperative liquid dynamics with the mean square displacement.
AB  - Literature data for picosecond mean square displacements show that the
      anharmonicity explains only about half of the fragility (with different fractions
      for different glass formers). The other half must be ascribed to the Adam-Gibbs
      mechanism of a growing cooperatively rearranging region. One can measure both
      influences separately by a simultaneous measurement of liquid and crystal in the
      coexistence region. 

PMID- 25375500
TI  - Microscopic description of flow defects and relaxation in metallic glasses.
AB  - The anelastic relaxation behavior of amorphous Al86.8Ni3.7Y9.5 was characterized
      in prolonged, quasistatic measurements, up to 1.1*10(8) s. The size-density
      distribution of potential shear transformation zones was determined from the
      data. We derive an expression for the distribution, based on a free-volume
      criterion for an atomic cluster being a potential shear transformation zone. The
      model is shown to be consistent with experiment.

PMID- 25375501
TI  - Potential energy landscape and inherent dynamics of a hard-sphere fluid.
AB  - Hard-sphere models exhibit many of the same kinds of supercooled-liquid behavior
      as more realistic models of liquids, but the highly nonanalytic character of
      their potentials makes it a challenge to think of that behavior in potential
      energy landscape terms. We show here that it is possible to calculate an
      important topological property of hard-sphere landscapes, the geodesic pathways
      through those landscapes, and to do so without artificially coarse-graining or
      softening the potential. We show, moreover, that the rapid growth of the lengths
      of those pathways with increasing packing fraction quantitatively predicts the
      precipitous decline in diffusion constants in a glass-forming hard-sphere mixture
      model. The geodesic paths themselves can be considered as defining the intrinsic
      dynamics of hard spheres, so it is also revealing to find that they (and
      therefore the features of the underlying potential energy landscape) correctly
      predict the occurrence of dynamic heterogeneity and nonzero values of the non
      Gaussian parameter. The success of these landscape predictions for the dynamics
      of such a singular model emphasizes that there is more to potential energy
      landscapes than is revealed by looking at the minima and saddle points. 

PMID- 25375502
TI  - Elasticity and plasticity in stiff and flexible oligomeric glasses.
AB  - In this paper we focus on the mechanical properties of oligomeric glasses
      (waxes), employing a microscopic model that provides, via numerical simulations,
      information about the shear modulus of such materials, the failure mechanism via
      plastic instabilities, and the geometric responses of the oligomers themselves to
      a mechanical load. We present a microscopic theory that explains the numerically
      observed phenomena, including an exact theory of the shear modulus and of the
      plastic instabilities, both local and system spanning. In addition we present a
      model to explain the geometric changes in the oligomeric chains under increasing
      strains. 

PMID- 25375503
TI  - Structure and interaction in the polymer-dependent reentrant phase behavior of a
      charged nanoparticle solution.
AB  - Small-angle neutron scattering (SANS) studies have been carried out to examine
      the evolution of interaction and structure in a nanoparticle (silica)-polymer
      (polyethylene glycol) system. The nanoparticle-polymer solution interestingly
      shows a reentrant phase behavior where the one-phase charged stabilized
      nanoparticles go through a two-phase system (nanoparticle aggregation) and back
      to one-phase as a function of polymer concentration. Such phase behavior arises
      because of the nonadsorption of polymer on nanoparticles and is governed by the
      interplay of polymer-induced attractive depletion with repulsive nanoparticle
      nanoparticle electrostatic and polymer-polymer interactions in different polymer
      concentration regimes. At low polymer concentrations, the electrostatic repulsion
      dominates over the depletion attraction. However, the increase in polymer
      concentration enhances the depletion attraction to give rise to the nanoparticle
      aggregation in the two-phase system. Further, the polymer-polymer repulsion at
      high polymer concentrations is believed to be responsible for the reentrance to
      one-phase behavior. The SANS data in polymer contrast-matched conditions have
      been modeled by a two-Yukawa potential accounting for both repulsive and
      attractive parts of total interaction potential between nanoparticles. Both of
      these interactions (repulsive and attractive) are found to be long range. The
      magnitude and the range of the depletion interaction increase with the polymer
      concentration leading to nanoparticle clustering. At higher polymer
      concentrations, the increased polymer-polymer repulsion reduces the depletion
      interaction leading to reentrant phase behavior. The nanoparticle clusters in the
      two-phase system are characterized by the surface fractal with simple cubic
      packing of nanoparticles within the clusters. The effect of varying ionic
      strength and polymer size in tuning the interaction has also been examined. 

PMID- 25375504
TI  - Mechanics of large folds in thin interfacial films.
AB  - A thin film confined to a liquid interface responds to uniaxial compression by
      wrinkling, and then by folding, that has been solved exactly before self-contact.
      Here, we address the mechanics of large folds, i.e., folds that absorb a length
      much larger than the wrinkle wavelength. With scaling arguments and numerical
      simulations, we show that the antisymmetric fold is energetically favorable and
      can absorb any excess length at zero pressure. Then, motivated by puzzles arising
      in the comparison of this simple model to experiments on lipid monolayers or
      capillary rafts, we discuss how to incorporate film weight, self-adhesion, or
      energy dissipation. 

PMID- 25375505
TI  - Evaporation-driven growth of large crystallized salt structures in a porous
      medium.
AB  - Subflorescence refers to crystallized salt structures that form inside a porous
      medium. We report a drying experiment revealing major development of
      subflorescence in the dry region of the porous medium away from the liquid zone.
      Using a combination of image analyses and numerical computations, we show that
      the growth is directly correlated to the evaporation flux distribution along the
      boundary of the growing salt structure. This indicates that the salt is
      transported into the domain occupied by the salt structure in the porous medium
      up to the structure periphery, where salt deposition takes place. This is
      confirmed when a growing salt structure encounters dry subflorescence formed
      earlier during the drying process. The dry subflorescence is reimbibed and
      resumes its growth. The analysis also suggests that the solution within the
      growing subflorescence is in equilibrium with the crystallized salt wall. These
      results shed light on the growth mechanisms of subflorescence, a phenomenon that
      can play a fundamental role in several important issues such as carbon dioxide
      sequestration or salt weathering. 

PMID- 25375506
TI  - Tuned Mullins-Sekerka instability: exact results.
AB  - Mullins-Sekerka's instability at 3D self-similar growth of a spherical seed
      crystal in an undercooled fluid is discussed. The exact solution of the
      linearized stability problem is obtained. It is quite different from the
      conventional results of the quasisteady approximation. The instability occurs
      much weaker, so that instead of exponential growth in time, unstable modes
      exhibit just power-law-growth. The relative growth rates of different modes vary
      in time and depend on their initial amplitudes. It allows control over the growth
      of each mode individually and tailoring the instability, to obtain a desired
      shape of the growing crystal at a given time. 

PMID- 25375507
TI  - Solidification in soft-core fluids: Disordered solids from fast solidification
      fronts.
AB  - Using dynamical density functional theory we calculate the speed of
      solidification fronts advancing into a quenched two-dimensional model fluid of
      soft-core particles. We find that solidification fronts can advance via two
      different mechanisms, depending on the depth of the quench. For shallow quenches,
      the front propagation is via a nonlinear mechanism. For deep quenches, front
      propagation is governed by a linear mechanism and in this regime we are able to
      determine the front speed via a marginal stability analysis. We find that the
      density modulations generated behind the advancing front have a characteristic
      scale that differs from the wavelength of the density modulation in thermodynamic
      equilibrium, i.e., the spacing between the crystal planes in an equilibrium
      crystal. This leads to the subsequent development of disorder in the solids that
      are formed. In a one-component fluid, the particles are able to rearrange to form
      a well-ordered crystal, with few defects. However, solidification fronts in a
      binary mixture exhibiting crystalline phases with square and hexagonal ordering
      generate solids that are unable to rearrange after the passage of the
      solidification front and a significant amount of disorder remains in the system. 

PMID- 25375508
TI  - Morphological study of elastic-plastic-brittle transitions in disordered media.
AB  - We use a spring lattice model with springs following a bilinear elastoplastic
      brittle constitutive behavior with spatial disorder in the yield and failure
      thresholds to study patterns of plasticity and damage evolution. The elastic
      perfectly plastic transition is observed to follow percolation scaling with the
      correlation length critical exponent nu~1.59, implying the universality class
      corresponding to the long-range correlated percolation. A quantitative analysis
      of the plastic strain accumulation reveals a dipolar anisotropy (for antiplane
      loading) which vanishes with increasing hardening modulus. A parametric study
      with hardening modulus and ductility controlled through the spring level
      constitutive response demonstrates a wide spectrum of behaviors with varying
      degree of coupling between plasticity and damage evolution. 

PMID- 25375509
TI  - Theoretical predictions of disclination loop growth for nematic liquid crystals
      under capillary confinement.
AB  - The combination of low elasticity modulus, anisotropy, and responsiveness to
      external fields drives the rich variety of experimentally observed pattern
      formation in nematic liquid crystals under capillary confinement. External fields
      of interest in technology and fundamental physics are flow fields,
      electromagnetic fields, and surface fields due to confinement. In this paper we
      present theoretical and simulation studies of the pattern formation of nematic
      liquid crystal disclination loops under capillary confinement including branching
      processes from a m=+1 disclination line to two m=+1/2 disclination curves that
      describe the postnucleation and growth regime of the textural transformation from
      radial to planar polar textures. The early postnucleation and growth of emerging
      disclination loops in cylindrical capillaries are characterized using analytical
      and computational methods based on the nematic elastica that takes into account
      line tension and line bending stiffness. Using subdiffusive growth and constant
      loop anisotropy, we found that the solution to the nematic elastica is a cusped
      elliptical geometry characterized by exponential curvature variations. The
      scaling laws that govern the loop growth reflect the tension to bending
      elasticity balance and reveal that the loop dilation rate depends on the
      curvature and normal velocity of the disclination. The line energy growth is
      accommodated by the decrease in branch-point curvature. These findings contribute
      to the evolving understanding of textural transformations in nematic liquid
      crystals under confinement using the nematic elastic methodology. 

PMID- 25375510
TI  - Theory of skyrmion states in liquid crystals.
AB  - Within the Oseen-Frank theory we derive numerically exact solutions for
      axisymmetric localized states in chiral liquid crystal layers with homeotropic
      anchoring. These solutions describe recently observed two-dimensional skyrmions
      in confinement-frustrated chiral nematics [P. J. Ackerman et al., Phys. Rev. E
      90, 012505 (2014)]. We stress that these solitonic states arise due to a
      fundamental stabilization mechanism responsible for the formation of skyrmions in
      cubic helimagnets and other noncentrosymmetric condensed-matter systems. 

PMID- 25375511
TI  - Beam-splitter switches based on zenithal bistable liquid-crystal gratings.
AB  - The tunable optical diffractive properties of zenithal bistable nematic liquid
      crystal gratings are theoretically investigated. The liquid-crystal orientation
      is rigorously solved via a tensorial formulation of the Landau-de Gennes theory
      and the optical transmission properties of the gratings are investigated via full
      wave finite-element frequency-domain simulations. It is demonstrated that by
      proper design the two stable states of the grating can provide nondiffracting and
      diffracting operation, the latter with equal power splitting among different
      diffraction orders. An electro-optic switching mechanism, based on dual-frequency
      nematic materials, and its temporal dynamics are further discussed. Such gratings
      provide a solution towards tunable beam-steering and beam-splitting components
      with extremely low power consumption. 

PMID- 25375512
TI  - Optics of short-pitch deformed-helix ferroelectric liquid crystals: symmetries,
      exceptional points, and polarization-resolved angular patterns.
AB  - In order to explore electric-field-induced transformations of polarization
      singularities in the polarization-resolved angular (conoscopic) patterns emerging
      after deformed-helix ferroelectric liquid crystal (DHFLC) cells with
      subwavelength helix pitch, we combine the transfer matrix formalism with the
      results for the effective dielectric tensor of biaxial FLCs evaluated using an
      improved technique of averaging over distorted helical structures. Within the
      framework of the transfer matrix method, we deduce a number of symmetry relations
      and show that the symmetry axis of L lines (curves of linear polarization) is
      directed along the major in-plane optical axis which rotates under the action of
      the electric field. When the angle between this axis and the polarization plane
      of incident linearly polarized light is above its critical value, the C points
      (points of circular polarization) appear in the form of symmetrically arranged
      chains of densely packed star-monstar pairs. We also emphasize the role of phase
      singularities of a different kind and discuss the enhanced electro-optic response
      of DHFLCs near the exceptional point where the condition of zero-field isotropy
      is fulfilled. 

PMID- 25375513
TI  - Ionic-content dependence of viscoelasticity of the lyotropic chromonic liquid
      crystal sunset yellow.
AB  - A lyotropic chromonic liquid crystal (LCLC) is an orientationally ordered system
      made by self-assembled aggregates of charged organic molecules in water, bound by
      weak noncovalent attractive forces and stabilized by electrostatic repulsions. We
      determine how the ionic content of the LCLC, namely, the presence of mono- and
      divalent salts and pH enhancing agent, alter the viscoelastic properties of the
      LCLC. Aqueous solutions of the dye sunset yellow with a uniaxial nematic order
      are used as an example. By applying a magnetic field to impose orientational
      deformations, we measure the splay K1, twist K2, and bend K3 elastic constants
      and rotation viscosity gamma1 as a function of concentration of additives. The
      data indicate that the viscoelastic parameters are influenced by ionic content in
      dramatic and versatile ways. For example, the monovalent salt NaCl decreases K3
      and K2 and increases gamma1, while an elevated pH decreases all the parameters.
      We attribute these features to the ion-induced changes in length and flexibility
      of building units of LCLC, the chromonic aggregates, a property not found in
      conventional thermotropic and lyotropic liquid crystals formed by covalently
      bound units of fixed length.

PMID- 25375514
TI  - Structure-sensitive bend elastic constants between piconewton and subnanonewton
      in diphenylacetylene-core-based liquid crystals.
AB  - Elastic constants in liquid crystals are known to be in the range of pico- and
      several-tens piconewton (pN). We report herein that a bend elastic constant, K33,
      remarkably varies depending on a slight modification of the chemical structure in
      an analogous series of calamitic liquid crystals. In contrast to the record-high
      bend elastic constants (hundreds pN or sub-nN) reported previously in a compound
      with an azo linkage, analogous compounds with tolan and ester linkages show
      several-tens pN and pN, respectively. X-ray diffraction studies of these
      compounds reveal that smectic-like layer structures (cybotacticclusters) are
      formed in the nematic phase of only the homologous compounds with an azo linkage,
      certifying the idea that the existence of cybotactic clusters strongly enhances
      K33. Two theoretical considerations were made: (1) Based on molecular
      conformation calculation, flat molecules that have high torsional potential
      energy, such as the one with an azo linkage, easily pack to form cybotactic
      clusters. (2) Theoretical estimation was made of how much cluster volume ratio is
      necessary to give about 100-times-larger K33s.

PMID- 25375515
TI  - Understanding the role of grafted polystyrene chain conformation in assembly of
      magnetic nanoparticles.
AB  - Polystyrene-grafted iron oxide nanoparticles have been shown to phase separate
      into ordered morphologies of strings, well-dispersed particles, and spherical
      aggregates at low graft densities in polymer matrices. In this work, small-angle
      neutron scattering experiments are performed to reveal the role of grafted chain
      conformation on nanoparticle assemblies. We demonstrate that chains grafted at
      low densities follow Gaussian statistics at any dispersion states. These results
      suggest that grafted chains are not distorted but remain Gaussian when particles
      are aggregated into strings. Small-angle x-ray and neutron scattering results
      show that matrix chains do not influence the formation of strings, but have a
      significant impact on the size and internal structure of aggregated particles. We
      conclude that spherical aggregates of nanoparticles with low polymer graft
      densities are akin to interpenetrating networks in which free matrix chains
      bridge the fractals of particles and control the cluster density. 

PMID- 25375516
TI  - Pulling-force-induced elongation and alignment effects on entanglement and
      knotting characteristics of linear polymers in a melt.
AB  - We employ a primitive path (PP) algorithm and the Gauss linking integral to study
      the degree of entanglement and knotting characteristics of linear polymer model
      chains in a melt under the action of a constant pulling force applied to selected
      chain ends. Our results for the amount of entanglement, the linking number, the
      average crossing number, the writhe of the chains and their PPs and the writhe of
      the entanglement strands all suggest a different response at the length scale of
      entanglement strands than that of the chains themselves and of the corresponding
      PPs. Our findings indicate that the chains first stretch at the level of
      entanglement strands and next the PP (tube) gets oriented with the "flow." These
      two phases of the extension and alignment of the chains coincide with two phases
      related to the disentanglement of the chains. Soon after the onset of external
      force the PPs attain a more entangled conformation, and the number of
      nontrivially linked end-to-end closed chains increases. Next, the chains
      disentangle continuously to attain an almost unentangled conformation. Using the
      linking matrix of the chains in the melt, we furthermore show that these phases
      are accompanied by a different scaling of the homogeneity of the global
      entanglement in the system. The homogeneity of the end-to-end closed chains first
      increases to a maximum and then decreases slowly to a value characterizing a
      completely unlinked system. 

PMID- 25375517
TI  - Simplified lattice model for polypeptide fibrillar transitions.
AB  - Polypeptide fibrillar transitions are studied using a simplified lattice model,
      modified from the three-state Potts model, where uniform residues as spins,
      placed on a cubic lattice, can interact with neighbors to form coil, helical,
      sheet, or fibrillar structure. Using the transfer matrix method and numerical
      calculations, we analyzed the partition function and construct phase diagrams.
      The model manifests phase transitions among coil, helix, sheet, and fibril
      through parameterizing bond coupling energy Eh,Es,Ef, structural entropies
      sh,ss,sf of helical, sheet, and fibrillar states, and number density rho. The
      phase diagrams show the transition sequence is basically governed by Eh, Es, and
      Ef, while the transition temperature is determined by the competition among Eh,
      Es, and Ef, as well as sh, ss, sf, and rho. Furthermore, the fibrillation is
      accompanied with an abrupt phase transition from coil, helix, or sheet to fibril
      even for short polypeptide length, resembling the feature of nucleation-growth
      process. The finite-size effect in specific heat at transitions for the
      nonfibrillation case can be described by the scaling form of lattice model. With
      rich phase-transition properties, our model provides a useful reference for
      protein aggregation experiments and modeling.

PMID- 25375518
TI  - Criteria for minimal model of driven polymer translocation.
AB  - While the characteristics of the driven translocation for asymptotically long
      polymers are well understood, this is not the case for finite-sized polymers,
      which are relevant for real-world experiments and simulation studies. Most
      notably, the behavior of the exponent alpha, which describes the scaling of the
      translocation time with polymer length, when the driving force fp in the pore is
      changed, is under debate. By Langevin dynamics simulations of regular and
      modified translocation models using the freely jointed-chain polymer model we
      find that a previously reported incomplete model, where the trans side and
      fluctuations were excluded, gives rise to characteristics that are in stark
      contradiction with those of the complete model, for which alpha increases with
      fp. Our results suggest that contribution due to fluctuations is important. We
      construct a minimal model where dynamics is completely excluded to show that
      close alignment with a full translocation model can be achieved. Our findings set
      very stringent requirements for a minimal model that is supposed to describe the
      driven polymer translocation correctly.

PMID- 25375519
TI  - Quantifying the degree of persistence in random amoeboid motion based on the
      Hurst exponent of fractional Brownian motion.
AB  - Amoebae explore their environment in a random way, unless external cues like,
      e.g., nutrients, bias their motion. Even in the absence of cues, however,
      experimental cell tracks show some degree of persistence. In this paper, we
      analyzed individual cell tracks in the framework of a linear mixed effects model,
      where each track is modeled by a fractional Brownian motion, i.e., a Gaussian
      process exhibiting a long-term correlation structure superposed on a linear
      trend. The degree of persistence was quantified by the Hurst exponent of
      fractional Brownian motion. Our analysis of experimental cell tracks of the
      amoeba Dictyostelium discoideum showed a persistent movement for the majority of
      tracks. Employing a sliding window approach, we estimated the variations of the
      Hurst exponent over time, which allowed us to identify points in time, where the
      correlation structure was distorted ("outliers"). Coarse graining of track data
      via down-sampling allowed us to identify the dependence of persistence on the
      spatial scale. While one would expect the (mode of the) Hurst exponent to be
      constant on different temporal scales due to the self-similarity property of
      fractional Brownian motion, we observed a trend towards stronger persistence for
      the down-sampled cell tracks indicating stronger persistence on larger time
      scales. 

PMID- 25375520
TI  - Diffusion and bulk flow in phloem loading: a theoretical analysis of the polymer
      trap mechanism for sugar transport in plants.
AB  - Plants create sugar in the mesophyll cells of their leaves by photosynthesis.
      This sugar, mostly sucrose, has to be loaded via the bundle sheath into the
      phloem vascular system (the sieve elements), where it is distributed to growing
      parts of the plant. We analyze the feasibility of a particular loading mechanism,
      active symplasmic loading, also called the polymer trap mechanism, where sucrose
      is transformed into heavier sugars, such as raffinose and stachyose, in the
      intermediary-type companion cells bordering the sieve elements in the minor veins
      of the phloem. Keeping the heavier sugars from diffusing back requires that the
      plasmodesmata connecting the bundle sheath with the intermediary cell act as
      extremely precise filters, which are able to distinguish between molecules that
      differ by less than 20% in size. In our modeling, we take into account the
      coupled water and sugar movement across the relevant interfaces, without
      explicitly considering the chemical reactions transforming the sucrose into the
      heavier sugars. Based on the available data for plasmodesmata geometry, sugar
      concentrations, and flux rates, we conclude that this mechanism can in principle
      function, but that it requires pores of molecular sizes. Comparing with the
      somewhat uncertain experimental values for sugar export rates, we expect the
      pores to be only 5%-10% larger than the hydraulic radius of the sucrose
      molecules. We find that the water flow through the plasmodesmata, which has not
      been quantified before, contributes only 10%-20% to the sucrose flux into the
      intermediary cells, while the main part is transported by diffusion. On the other
      hand, the subsequent sugar translocation into the sieve elements would very
      likely be carried predominantly by bulk water flow through the plasmodesmata.
      Thus, in contrast to apoplasmic loaders, all the necessary water for phloem
      translocation would be supplied in this way with no need for additional water
      uptake across the plasma membranes of the phloem. 

PMID- 25375521
TI  - Hydration-dependent dynamic crossover phenomenon in protein hydration water.
AB  - The characteristic relaxation time tau of protein hydration water exhibits a
      strong hydration level h dependence. The dynamic crossover is observed when h is
      higher than the monolayer hydration level hc=0.2-0.25 and becomes more visible as
      h increases. When h is lower than hc, tau only exhibits Arrhenius behavior in the
      measured temperature range. The activation energy of the Arrhenius behavior is
      insensitive to h, indicating a local-like motion. Moreover, the h dependence of
      the crossover temperature shows that the protein dynamic transition is not
      directly or solely induced by the dynamic crossover in the hydration water.

PMID- 25375522
TI  - Contact time periods in immunological synapse.
AB  - This paper resolves the long standing debate as to the proper time scale <tau> of
      the onset of the immunological synapse bond, the noncovalent chemical bond
      defining the immune pathways involving T cells and antigen presenting cells.
      Results from our model calculations show <tau> to be of the order of seconds
      instead of minutes. Close to the linearly stable regime, we show that in between
      the two critical spatial thresholds defined by the integrin:ligand pair (Delta2~
      40-45 nm) and the T-cell receptor TCR:peptide-major-histocompatibility-complex
      pMHC bond (Delta1~ 14-15 nm), <tau> grows monotonically with increasing
      coreceptor bond length separation delta (= Delta2-Delta1~ 26-30 nm) while <tau>
      decays with Delta1 for fixed Delta2. The nonuniversal delta-dependent power-law
      structure of the probability density function further explains why only the
      TCR:pMHC bond is a likely candidate to form a stable synapse.

PMID- 25375523
TI  - Sensitivity and entanglement in the avian chemical compass.
AB  - The radical pair mechanism can help to explain avian orientation and navigation.
      Some evidence indicates that the intensity of external magnetic fields plays an
      important role in avian navigation. In this paper, using a two-stage model, we
      demonstrate that birds could reasonably detect the directions of geomagnetic
      fields and gradients of these fields using a yield-based chemical compass that is
      sensitive enough for navigation. Also, we find that the lifetime of entanglement
      in this proposed compass is angle dependent and long enough to allow adequate
      electron transfer between molecules. 

PMID- 25375524
TI  - Polymer translocation through a nanopore driven by binding particles: influence
      of chain rigidity.
AB  - We investigate the influence of chain rigidity on the dynamics of polymer
      translocation in the presence of binding particles (BPs) through a nanopore using
      two-dimensional Langevin dynamics simulations. With increasing chain rigidity
      kappa, the mean translocation time <tau> increases monotonically due to an
      increase in the radius of gyration and a decrease in the center of mass velocity.
      Particularly for weak binding, we further find that <tau> shows a power-law
      behavior with the persistence length lp. Analysis indicates a scaling relation
      between the average velocity of the center of mass of a chain <vc.m.> and lp. As
      the chain becomes stiffer, the distribution of the translocation time tau
      approximates the Gaussian distribution and gets broader with the peak position
      being shifted towards longer translocation time. The corresponding translocation
      coordinate smax of the maximum waiting time gets smaller with increasing chain
      rigidity. Finally, under an extremely low BP concentration, <tau> shows a minimum
      for small kappa, while it decreases monotonically for large kappa with increasing
      binding energy. Our results suggest a nontrivial effect of the intrinsic property
      of chains on the dynamics of polymer translocation driven by BPs.

PMID- 25375525
TI  - Calibrated Langevin-dynamics simulations of intrinsically disordered proteins.
AB  - We perform extensive coarse-grained (CG) Langevin dynamics simulations of
      intrinsically disordered proteins (IDPs), which possess fluctuating
      conformational statistics between that for excluded volume random walks and
      collapsed globules. Our CG model includes repulsive steric, attractive
      hydrophobic, and electrostatic interactions between residues and is calibrated to
      a large collection of single-molecule fluorescence resonance energy transfer data
      on the interresidue separations for 36 pairs of residues in five IDPs: alpha-,
      beta-, and gamma-synuclein, the microtubule-associated protein tau, and
      prothymosin alpha. We find that our CG model is able to recapitulate the average
      interresidue separations regardless of the choice of the hydrophobicity scale,
      which shows that our calibrated model can robustly capture the conformational
      dynamics of IDPs. We then employ our model to study the scaling of the radius of
      gyration with chemical distance in 11 known IDPs. We identify a strong
      correlation between the distance to the dividing line between folded proteins and
      IDPs in the mean charge and hydrophobicity space and the scaling exponent of the
      radius of gyration with chemical distance along the protein. 

PMID- 25375526
TI  - Quantum dynamics of the avian compass.
AB  - The ability of migratory birds to orient relative to the Earth's magnetic field
      is believed to involve a coherent superposition of two spin states of a radical
      electron pair. However, the mechanism by which this coherence can be maintained
      in the face of strong interactions with the cellular environment has remained
      unclear. This paper addresses the problem of decoherence between two electron
      spins due to hyperfine interaction with a bath of spin-1/2 nuclei. Dynamics of
      the radical pair density matrix are derived and shown to yield a simple mechanism
      for sensing magnetic field orientation. Rates of dephasing and decoherence are
      calculated ab initio and found to yield millisecond coherence times, consistent
      with behavioral experiments. 

PMID- 25375527
TI  - Effect of radio frequency fields on the radical pair magnetoreception model.
AB  - Although the radical pair (RP) model is widely accepted for birds' orientation,
      the physical mechanism of it is still not fully understood. In this paper we
      consider the RP model in the total angular-momentum representation and clearly
      show a detailed mechanism for orientation. When only the vertical hyperfine (HF)
      coupling component is considered, analytical expressions of singlet yield angular
      profiles are obtained with and without considering the radio frequency field, and
      when the horizontal HF coupling components are considered, a numerical
      calculation of the singlet yield is given. Based on these analytical and
      numerical results we present a detailed account of the following issues: how the
      HF coupling induces the singlet-triplet conversion; why the vertical radio
      frequency field can disorient the birds, while the parallel one cannot; and why
      the birds are able to "train" to different field strengths. Finally, we consider
      a multinuclei RP model. 

PMID- 25375528
TI  - Determination of effective brain connectivity from functional connectivity using
      propagator-based interferometry and neural field theory with application to the
      corticothalamic system.
AB  - It is shown how to compute both direct and total effective connection matrices
      (deCMs and teCMs), which embody the strengths of neural connections between
      regions, from correlation-based functional CMs using propagator-based
      interferometry, a method that stems from geophysics and acoustics, coupled with
      the recent identification of deCMs and teCMs with bare and dressed propagators,
      respectively. The approach incorporates excitatory and inhibitory connections,
      multiple structures and populations, and measurement effects. The propagator is
      found for a generalized scalar wave equation derived from neural field theory,
      and expressed in terms of neural activity correlations and covariances, and wave
      damping rates. It is then related to correlation matrices that are commonly used
      to express functional and effective connectivities in the brain. The results are
      illustrated in analytically tractable test cases. 

PMID- 25375529
TI  - Cryogenic x-ray diffraction microscopy utilizing high-pressure cryopreservation.
AB  - We present cryo x-ray diffraction microscopy of high-pressure-cryofixed bacteria
      and report high-convergence imaging with multiple image reconstructions. Hydrated
      D. radiodurans cells were cryofixed at 200 MPa pressure into ~10-MUm-thick water
      layers and their unstained, hydrated cellular environments were imaged by phasing
      diffraction patterns, reaching sub-30-nm resolutions with hard x-rays.
      Comparisons were made with conventional ambient-pressure-cryofixed samples, with
      respect to both coherent small-angle x-ray scattering and the image
      reconstruction. The results show a correlation between the level of background
      ice signal and phasing convergence, suggesting that phasing difficulties with
      frozen-hydrated specimens may be caused by high-background ice scattering. 

PMID- 25375530
TI  - Entropy production of a steady-growth cell with catalytic reactions.
AB  - Cells generally convert external nutrient resources to support metabolism and
      growth. Understanding the thermodynamic efficiency of this conversion is
      essential to determine the general characteristics of cellular growth. Using a
      simple protocell model with catalytic reaction dynamics to synthesize the
      necessary enzyme and membrane components from nutrients, the entropy production
      per unit-cell-volume growth is calculated analytically and numerically based on
      the rate equation for chemical kinetics and linear nonequilibrium thermodynamics.
      The minimal entropy production per unit-cell growth is found to be achieved at a
      nonzero nutrient uptake rate rather than at a quasistatic limit as in the
      standard Carnot engine. This difference appears because the equilibration
      mediated by the enzyme exists only within cells that grow through enzyme and
      membrane synthesis. Optimal nutrient uptake is also confirmed by protocell models
      with many chemical components synthesized through a catalytic reaction network.
      The possible relevance of the identified optimal uptake to optimal yield for
      cellular growth is also discussed. 

PMID- 25375532
TI  - Simple analytical model of evapotranspiration in the presence of roots.
AB  - Evaporation of water out of a soil involves complicated and well-debated
      mechanisms. When plant roots are added into the soil, water transfer between the
      soil and the outside environment is even more complicated. Indeed, plants provide
      an additional process of water transfer. Water is pumped by the roots, channeled
      to the leaf surface, and released into the surrounding air by a process called
      transpiration. Prediction of the evapotranspiration of water over time in the
      presence of roots helps keep track of the amount of water that remains in the
      soil. Using a controlled visual setup of a two-dimensional model soil consisting
      of monodisperse glass beads, we perform experiments on actual roots grown under
      different relative humidity conditions. We record the total water mass loss in
      the medium and the position of the evaporating front that forms within the
      medium. We then develop a simple analytical model that predicts the position of
      the evaporating front as a function of time as well as the total amount of water
      that is lost from the medium due to the combined effects of evaporation and
      transpiration. The model is based on fundamental principles of evaporation fluxes
      and includes empirical assumptions on the quantity of open stomata in the leaves,
      where water transpiration occurs. Comparison between the model and experimental
      results shows excellent prediction of the position of the evaporating front as
      well as the total mass loss from evapotranspiration in the presence of roots. The
      model also provides a way to predict the lifetime of a plant. 

PMID- 25375531
TI  - Wang-Landau sampling in face-centered-cubic hydrophobic-hydrophilic lattice model
      proteins.
AB  - Finding the global minimum-energy structure is one of the main problems of
      protein structure prediction. The face-centered-cubic (fcc) hydrophobic
      hydrophilic (HP) lattice model can reach high approximation ratios of real
      protein structures, so the fcc lattice model is a good choice to predict the
      protein structures. The lacking of an effective global optimization method is the
      key obstacle in solving this problem. The Wang-Landau sampling method is
      especially useful for complex systems with a rough energy landscape and has been
      successfully applied to solving many optimization problems. We apply the improved
      Wang-Landau (IWL) sampling method, which incorporates the generation of an
      initial conformation based on the greedy strategy and the neighborhood strategy
      based on pull moves into the Wang-Landau sampling method to predict the protein
      structures on the fcc HP lattice model. Unlike conventional Monte Carlo
      simulations that generate a probability distribution at a given temperature, the
      Wang-Landau sampling method can estimate the density of states accurately via a
      random walk, which produces a flat histogram in energy space. We test 12 general
      benchmark instances on both two-dimensional and three-dimensional (3D) fcc HP
      lattice models. The lowest energies by the IWL sampling method are as good as or
      better than those of other methods in the literature for all instances. We then
      test five sets of larger-scale instances, denoted by the S, R, F90, F180, and
      CASP target instances on the 3D fcc HP lattice model. The numerical results show
      that our algorithm performs better than the other five methods in the literature
      on both the lowest energies and the average lowest energies in all runs. The IWL
      sampling method turns out to be a powerful tool to study the structure prediction
      of the fcc HP lattice model proteins. 

PMID- 25375533
TI  - Muscle activation described with a differential equation model for large
      ensembles of locally coupled molecular motors.
AB  - Molecular motors, by turning chemical energy into mechanical work, are
      responsible for active cellular processes. Often groups of these motors work
      together to perform their biological role. Motors in an ensemble are coupled and
      exhibit complex emergent behavior. Although large motor ensembles can be modeled
      with partial differential equations (PDEs) by assuming that molecules function
      independently of their neighbors, this assumption is violated when motors are
      coupled locally. It is therefore unclear how to describe the ensemble behavior of
      the locally coupled motors responsible for biological processes such as calcium
      dependent skeletal muscle activation. Here we develop a theory to describe
      locally coupled motor ensembles and apply the theory to skeletal muscle
      activation. The central idea is that a muscle filament can be divided into two
      phases: an active and an inactive phase. Dynamic changes in the relative size of
      these phases are described by a set of linear ordinary differential equations
      (ODEs). As the dynamics of the active phase are described by PDEs, muscle
      activation is governed by a set of coupled ODEs and PDEs, building on previous
      PDE models. With comparison to Monte Carlo simulations, we demonstrate that the
      theory captures the behavior of locally coupled ensembles. The theory also
      plausibly describes and predicts muscle experiments from molecular to whole
      muscle scales, suggesting that a micro- to macroscale muscle model is within
      reach. 

PMID- 25375534
TI  - Noise, transient dynamics, and the generation of realistic interspike interval
      variation in square-wave burster neurons.
AB  - First return maps of interspike intervals for biological neurons that generate
      repetitive bursts of impulses can display stereotyped structures (neuronal
      signatures). Such structures have been linked to the possibility of multicoding
      and multifunctionality in neural networks that produce and control rhythmical
      motor patterns. In some cases, isolating the neurons from their synaptic network
      reveals irregular, complex signatures that have been regarded as evidence of
      intrinsic, chaotic behavior. We show that incorporation of dynamical noise into
      minimal neuron models of square-wave bursting (either conductance-based or
      abstract) produces signatures akin to those observed in biological examples,
      without the need for fine tuning of parameters or ad hoc constructions for
      inducing chaotic activity. The form of the stochastic term is not strongly
      constrained and can approximate several possible sources of noise, e.g., random
      channel gating or synaptic bombardment. The cornerstone of this signature
      generation mechanism is the rich, transient, but deterministic dynamics inherent
      in the square-wave (saddle-node and homoclinic) mode of neuronal bursting. We
      show that noise causes the dynamics to populate a complex transient scaffolding
      or skeleton in state space, even for models that (without added noise) generate
      only periodic activity (whether in bursting or tonic spiking mode). 

PMID- 25375535
TI  - Retrodictive derivation of the radical-ion-pair master equation and Monte Carlo
      simulation with single-molecule quantum trajectories.
AB  - Radical-ion-pair reactions, central in photosynthesis and the avian magnetic
      compass mechanism, have been recently shown to be a paradigm system for applying
      quantum information science in a biochemical setting. The fundamental quantum
      master equation describing radical-ion-pair reactions is still under debate. Here
      we use quantum retrodiction to formally refine the theory put forward in the
      paper by Kominis [I. K. Kominis, Phys. Rev. E 83, 056118 (2011)]. We also provide
      a rigorous analysis of the measure of singlet-triplet coherence required for
      deriving the radical-pair master equation. A Monte Carlo simulation with single
      molecule quantum trajectories supports the self-consistency of our approach. 

PMID- 25375536
TI  - Geometrical model for malaria parasite migration in structured environments.
AB  - Malaria is transmitted to vertebrates via a mosquito bite, during which rodlike
      and crescent-shaped parasites, called sporozoites, are injected into the skin of
      the host. Searching for a blood capillary to penetrate, sporozoites move quickly
      in locally helical trajectories, that are frequently perturbed by interactions
      with the extracellular environment. Here we present a theoretical analysis of the
      active motility of sporozoites in a structured environment. The sporozoite is
      modelled as a self-propelled rod with spontaneous curvature and bending rigidity.
      It interacts with hard obstacles through collision rules inferred from
      experimental observation of two-dimensional sporozoite movement in pillar arrays.
      Our model shows that complex motion patterns arise from the geometrical shape of
      the parasite and that its mechanical flexibility is crucial for stable migration
      patterns. Extending the model to three dimensions reveals that a bent and twisted
      rod can associate to cylindrical obstacles in a manner reminiscent of the
      association of sporozoites to blood capillaries, supporting the notion of a
      prominent role of cell shape during malaria transmission. 

PMID- 25375537
TI  - Viral capsids: kinetics of assembly under transient conditions and kinetics of
      disassembly.
AB  - The available kinetic models of assembly of viral protein capsids are focused
      primarily on the situations in vitro where the amount of protein is fixed. In
      vivo, however, the viral protein synthesis and capsid assembly occur under
      transient conditions in parallel with viral genome replication. Herein, a kinetic
      model describing the latter case of capsid assembly is proposed with emphasis on
      the period corresponding to the initial stage of viral genome replication. The
      analysis is aimed at small icosahedral capsids. With biologically reasonable
      values of model parameters, the model predicts rapid exponential growth of the
      populations of monomers and fully assembled capsids during the transient period
      of genome replication. Under the subsequent steady-state conditions with respect
      to replication, the monomer population is predicted to be nearly constant while
      the number of fully assembled capsids increases linearly. The kinetics of capsid
      disassembly, described briefly as well under conditions of negligible monomer
      concentration, exhibit a short induction period when the number of proteins in a
      capsid is only slightly smaller than in the beginning, followed by more rapid
      protein detachment. According to calculations, the latter kinetics may strongly
      depend on protein degradation. 

PMID- 25375538
TI  - Junctional angle of a bihanded helix.
AB  - Helical filaments having sections of reversed chirality are common phenomena in
      the biological realm. The apparent angle between the two sections of opposite
      handedness provides information about the geometry and elasticity of the
      junctional region. In this paper, the governing differential equations for the
      local helical axis are developed, and asymptotic solutions of the governing
      equations are solved by perturbation theory. The asymptotic solutions are
      compared with the corresponding numerical solutions, and the relative error at
      second order is found to be less than 1.5% over a range of biologically relevant
      curvature and torsion values from 0 to 1/2 in dimensionless units. 

PMID- 25375539
TI  - Generalized cable formalism to calculate the magnetic field of single neurons and
      neuronal populations.
AB  - Neurons generate magnetic fields which can be recorded with macroscopic
      techniques such as magnetoencephalography. The theory that accounts for the
      genesis of neuronal magnetic fields involves dendritic cable structures in
      homogeneous resistive extracellular media. Here we generalize this model by
      considering dendritic cables in extracellular media with arbitrarily complex
      electric properties. This method is based on a multiscale mean-field theory where
      the neuron is considered in interaction with a "mean" extracellular medium
      (characterized by a specific impedance). We first show that, as expected, the
      generalized cable equation and the standard cable generate magnetic fields that
      mostly depend on the axial current in the cable, with a moderate contribution of
      extracellular currents. Less expected, we also show that the nature of the
      extracellular and intracellular media influence the axial current, and thus also
      influence neuronal magnetic fields. We illustrate these properties by numerical
      simulations and suggest experiments to test these findings. 

PMID- 25375540
TI  - Energetics of active fluctuations in living cells.
AB  - The nonequilibrium activity taking place in a living cell can be monitored with a
      tracer embedded in the medium. While microrheology experiments based on optical
      manipulation of such probes have become increasingly standard, we put forward a
      number of experiments with alternative protocols that, we claim, will provide
      insight into the energetics of active fluctuations. These are based on either
      performing thermodynamiclike cycles in control-parameter space or determining
      response to external perturbations of the confining trap beyond simple
      translation. We illustrate our proposals on an active itinerant Brownian
      oscillator modeling the dynamics of a probe embedded in a living medium. 

PMID- 25375541
TI  - High-pressure dynamics of hydrated protein in bioprotective trehalose
      environment.
AB  - We present a pressure-dependence study of the dynamics of lysozyme protein powder
      immersed in deuterated alpha,alpha-trehalose environment via quasielastic neutron
      scattering (QENS). The goal is to assess the baroprotective benefits of trehalose
      on biomolecules by comparing the findings with those of a trehalose-free
      reference study. While the mean-square displacement of the trehalose-free protein
      (hydrated to dD2O?40 w%) as a whole, is reduced by increasing pressure, the
      actual observable relaxation dynamics in the picoseconds to nanoseconds time
      range remains largely unaffected by pressure--up to the maximum investigated
      pressure of 2.78(2) Kbar. Our observation is independent of whether or not the
      protein is mixed with the deuterated sugar. This suggests that the hydrated
      protein's conformational states at atmospheric pressure remain unaltered by
      hydrostatic pressures, below 2.78 Kbar. We also found the QENS response to be
      totally recoverable after ambient pressure conditions are restored. Small-angle
      neutron diffraction measurements confirm that the protein-protein correlation
      remains undisturbed. We observe, however, a clear narrowing of the QENS response
      as the temperature is decreased from 290 to 230 K in both cases, which we
      parametrize using the Kohlrausch-Williams-Watts stretched exponential model. Only
      the fraction of protons that are immobile on the accessible time window of the
      instrument, referred to as the elastic incoherent structure factor, is observably
      sensitive to pressure, increasing only marginally but systematically with
      increasing pressure.

PMID- 25375542
TI  - Nonequivalence of updating rules in evolutionary games under high mutation rates.
AB  - Moran processes are often used to model selection in evolutionary simulations.
      The updating rule in Moran processes is a birth-death process, i. e., selection
      according to fitness of an individual to give birth, followed by the death of a
      random individual. For well-mixed populations with only two strategies this
      updating rule is known to be equivalent to selecting unfit individuals for death
      and then selecting randomly for procreation (biased death-birth process). It is,
      however, known that this equivalence does not hold when considering structured
      populations. Here we study whether changing the updating rule can also have an
      effect in well-mixed populations in the presence of more than two strategies and
      high mutation rates. We find, using three models from different areas of
      evolutionary simulation, that the choice of updating rule can change model
      results. We show, e. g., that going from the birth-death process to the death
      birth process can change a public goods game with punishment from containing
      mostly defectors to having a majority of cooperative strategies. From the
      examples given we derive guidelines indicating when the choice of the updating
      rule can be expected to have an impact on the results of the model. 

PMID- 25375543
TI  - Effect of individual behavior on epidemic spreading in activity-driven networks.
AB  - In this work we study the effect of behavioral changes of individuals on the
      propagation of epidemic diseases. Specifically, we consider a susceptible
      infected-susceptible model over a network of contacts that evolves in a time
      scale that is comparable to the individual disease dynamics. The phenomenon is
      modeled in the context of activity-driven networks, in which contacts occur on
      the basis of activity potentials. To offer insight into behavioral strategies
      targeting both susceptible and infected individuals, we consider two separate
      behaviors that may emerge in respiratory syndromes and sexually transmitted
      infections. The first is related to a reduction in the activity of infected
      individuals due to quarantine or illness. The second is instead associated with a
      selfish self-protective behavior of susceptible individuals, who tend to reduce
      contact with the rest of the population on the basis of a risk perception.
      Numerical and theoretical results suggest that behavioral changes could have a
      beneficial effect on the disease spreading, by increasing the epidemic threshold
      and decreasing the steady-state fraction of infected individuals. 

PMID- 25375544
TI  - Walk-based measure of balance in signed networks: detecting lack of balance in
      social networks.
AB  - There is a longstanding belief that in social networks with simultaneous friendly
      and hostile interactions (signed networks) there is a general tendency to a
      global balance. Balance represents a state of the network with a lack of
      contentious situations. Here we introduce a method to quantify the degree of
      balance of any signed (social) network. It accounts for the contribution of all
      signed cycles in the network and gives, in agreement with empirical evidence,
      more weight to the shorter cycles than to the longer ones. We found that,
      contrary to what is generally believed, many signed social networks, in
      particular very large directed online social networks, are in general very poorly
      balanced. We also show that unbalanced states can be changed by tuning the
      weights of the social interactions among the agents in the network. 

PMID- 25375545
TI  - Epidemic spreading on complex networks with general degree and weight
      distributions.
AB  - The spread of disease on complex networks has attracted wide attention in the
      physics community. Recent works have demonstrated that heterogeneous degree and
      weight distributions have a significant influence on the epidemic dynamics. In
      this study, a novel edge-weight-based compartmental approach is developed to
      estimate the epidemic threshold and epidemic size (final infected density) on
      networks with general degree and weight distributions, and a remarkable agreement
      with numerics is obtained. Even in complex networks with the strong heterogeneous
      degree and weight distributions, this approach is used. We then propose an edge
      weight-based removal strategy with different biases and find that such a strategy
      can effectively control the spread of epidemic when the highly weighted edges are
      preferentially removed, especially when the weight distribution of a network is
      extremely heterogenous. The theoretical results from the suggested method can
      accurately predict the above removal effectiveness. 

PMID- 25375546
TI  - Edge orientation for optimizing controllability of complex networks.
AB  - Recently, as the controllability of complex networks attracts much attention, how
      to design and optimize the controllability of networks has become a common and
      urgent problem in the field of controlling complex networks. Previous work
      focused on the structural perturbation and neglected the role of edge direction
      to optimize the network controllability. In a recent work [Phys. Rev. Lett. 103,
      228702 (2009)], the authors proposed a simple method to enhance the
      synchronizability of networks by assignment of link direction while keeping
      network topology unchanged. However, the controllability is fundamentally
      different from synchronization. In this work, we systematically propose the
      definition of assigning direction to optimize controllability, which is called
      the edge orientation for optimal controllability problem (EOOC). To solve the
      EOOC problem, we construct a switching network and transfer the EOOC problem to
      find the maximum independent set of the switching network. We prove that the
      principle of our optimization method meets the sense of unambiguity and optimum
      simultaneously. Furthermore, the relationship between the degree-degree
      correlations and EOOC are investigated by experiments. The results show that the
      disassortativity pattern could weaken the orientation for optimal
      controllability, while the assortativity pattern has no correlation with EOOC.
      All the experimental results of this work verify that the network structure
      determines the network controllability and the optimization effects. 

PMID- 25375547
TI  - How memory generates heterogeneous dynamics in temporal networks.
AB  - Empirical temporal networks display strong heterogeneities in their dynamics,
      which profoundly affect processes taking place on these networks, such as rumor
      and epidemic spreading. Despite the recent wealth of data on temporal networks,
      little work has been devoted to the understanding of how such heterogeneities can
      emerge from microscopic mechanisms at the level of nodes and links. Here we show
      that long-term memory effects are present in the creation and disappearance of
      links in empirical networks. We thus consider a simple generative modeling
      framework for temporal networks able to incorporate these memory mechanisms. This
      allows us to study separately the role of each of these mechanisms in the
      emergence of heterogeneous network dynamics. In particular, we show analytically
      and numerically how heterogeneous distributions of contact durations, of
      intercontact durations, and of numbers of contacts per link emerge. We also study
      the individual effect of heterogeneities on dynamical processes, such as the
      paradigmatic susceptible-infected epidemic spreading model. Our results confirm
      in particular the crucial role of the distributions of intercontact durations and
      of the numbers of contacts per link. 

PMID- 25375548
TI  - Triadic closure as a basic generating mechanism of communities in complex
      networks.
AB  - Most of the complex social, technological, and biological networks have a
      significant community structure. Therefore the community structure of complex
      networks has to be considered as a universal property, together with the much
      explored small-world and scale-free properties of these networks. Despite the
      large interest in characterizing the community structures of real networks, not
      enough attention has been devoted to the detection of universal mechanisms able
      to spontaneously generate networks with communities. Triadic closure is a natural
      mechanism to make new connections, especially in social networks. Here we show
      that models of network growth based on simple triadic closure naturally lead to
      the emergence of community structure, together with fat-tailed distributions of
      node degree and high clustering coefficients. Communities emerge from the initial
      stochastic heterogeneity in the concentration of links, followed by a cycle of
      growth and fragmentation. Communities are the more pronounced, the sparser the
      graph, and disappear for high values of link density and randomness in the
      attachment procedure. By introducing a fitness-based link attractivity for the
      nodes, we find a phase transition where communities disappear for high
      heterogeneity of the fitness distribution, but a different mesoscopic
      organization of the nodes emerges, with groups of nodes being shared between just
      a few superhubs, which attract most of the links of the system. 

PMID- 25375549
TI  - Nonlinear growth and condensation in multiplex networks.
AB  - Different types of interactions coexist and coevolve to shape the structure and
      function of a multiplex network. We propose here a general class of growth models
      in which the various layers of a multiplex network coevolve through a set of
      nonlinear preferential attachment rules. We show, both numerically and
      analytically, that by tuning the level of nonlinearity these models allow us to
      reproduce either homogeneous or heterogeneous degree distributions, together with
      positive or negative degree correlations across layers. In particular, we derive
      the condition for the appearance of a condensed state in which one node in each
      layer attracts an extensive fraction of all the edges. 

PMID- 25375550
TI  - Intergroup information exchange drives cooperation in the public goods game.
AB  - In this paper we explore the onset of cooperative traits in the public goods
      game. This well-known game involves N-agent interactions and thus reproduces a
      large number of social scenarios in which cooperation appears to be essential.
      Many studies have recently addressed how the structure of the interaction
      patterns influences the emergence of cooperation. Here we study how information
      about the payoffs collected by each individual in the different groups it
      participates in influences the decisions made by its group partners. Our results
      point out that cross-information plays a fundamental and positive role in the
      evolution of cooperation for different versions of the public goods game and
      different interaction structures. 

PMID- 25375551
TI  - Propensity and stickiness in the naming game: tipping fractions of minorities.
AB  - Agent-based models of the binary naming game are generalized here to represent a
      family of models parameterized by the introduction of two continuous parameters.
      These parameters define varying listener-speaker interactions on the individual
      level with one parameter controlling the speaker and the other controlling the
      listener of each interaction. The major finding presented here is that the
      generalized naming game preserves the existence of critical thresholds for the
      size of committed minorities. Above such threshold, a committed minority causes a
      fast (in time logarithmic in size of the network) convergence to consensus, even
      when there are other parameters influencing the system. Below such threshold,
      reaching consensus requires time exponential in the size of the network.
      Moreover, the two introduced parameters cause bifurcations in the stabilities of
      the system's fixed points and may lead to changes in the system's consensus. 

PMID- 25375552
TI  - Coherence index and curvelet transformation for denoising geophysical data.
AB  - Geophysical data contain stochastic noise that may mask their useful content. For
      example, ground roll (GR) is a coherent noise that is present in seismic data.
      Thus, such data are usually a mixture of useful information and useless coherent
      noise. The latter masks the relevant geologic information that seismic records
      contain, and its removal has always been a problem of fundamental importance. We
      propose a denoising method based on the curvelet transformation (CT), a
      multiscale transformation with strong directional character that provides an
      optimal representation of objects that have discontinuities along their edges. An
      algorithm is presented for processing and denoising of geophysical data. As an
      example, we apply the method to seismic images that are contaminated with the GR
      noise. First, the coherence index (CI), which represents a measure of the amount
      of energy contained in the most coherent modes of Karhunen-Loeve transform for
      any given segment of the data, is computed. The contaminated region of the data
      is then identified as the maximum region of the CI. After demarcating the
      contaminated segment, the CT is used to eliminate the noise. The method removes
      the noise with negligible distortion of the data's noncontaminated region. It is
      also significantly more efficient computationallty than the previous methods. The
      use of the method is demonstrated by its application to synthetic, as well as
      actual, seismic data for hydrocarbon reservoirs. 

PMID- 25375553
TI  - Fourier decomposition of payoff matrix for symmetric three-strategy games.
AB  - In spatial evolutionary games the payoff matrices are used to describe pair
      interactions among neighboring players located on a lattice. Now we introduce a
      way how the payoff matrices can be built up as a sum of payoff components
      reflecting basic symmetries. For the two-strategy games this decomposition
      reproduces interactions characteristic to the Ising model. For the three-strategy
      symmetric games the Fourier components can be classified into four types
      representing games with self-dependent and cross-dependent payoffs, variants of
      three-strategy coordinations, and the rock-scissors-paper (RSP) game. In the
      absence of the RSP component the game is a potential game. The resultant
      potential matrix has been evaluated. The general features of these systems are
      analyzed when the game is expressed by the linear combinations of these
      components. 

PMID- 25375554
TI  - Collision-free nonuniform dynamics within continuous optimal velocity models.
AB  - Optimal velocity (OV) car-following models give with few parameters stable stop
      and -go waves propagating like in empirical data. Unfortunately, classical OV
      models locally oscillate with vehicles colliding and moving backward. In order to
      solve this problem, the models have to be completed with additional parameters.
      This leads to an increase of the complexity. In this paper, a new OV model with
      no additional parameters is defined. For any value of the inputs, the model is
      intrinsically asymmetric and collision-free. This is achieved by using a first
      order ordinary model with two predecessors in interaction, instead of the usual
      inertial delayed first-order or second-order models coupled with the predecessor.
      The model has stable uniform solutions as well as various stable stop-and -go
      patterns with bimodal distribution of the speed. As observable in real data, the
      modal speed values in congested states are not restricted to the free flow speed
      and zero. They depend on the form of the OV function. Properties of linear,
      concave, convex, or sigmoid speed functions are explored with no limitation due
      to collisions. 

PMID- 25375555
TI  - Local and global epidemic outbreaks in populations moving in inhomogeneous
      environments.
AB  - We study disease spreading in a system of agents moving in a space where the
      force of infection is not homogeneous. Agents are random walkers that
      additionally execute long-distance jumps, and the plane in which they move is
      divided into two regions where the force of infection takes different values. We
      show the onset of a local epidemic threshold and a global one and explain them in
      terms of mean-field approximations. We also elucidate the critical role of the
      agent velocity, jump probability, and density parameters in achieving the
      conditions for local and global outbreaks. Finally, we show that the results are
      independent of the specific microscopic rules adopted for agent motion, since a
      similar behavior is also observed for the distribution of agent velocity based on
      a truncated power law, which is a model often used to fit real data on motion
      patterns of animals and humans. 

PMID- 25375556
TI  - Turing patterns in multiplex networks.
AB  - The theory of patterns formation for a reaction-diffusion system defined on a
      multiplex is developed by means of a perturbative approach. The interlayer
      diffusion constants act as a small parameter in the expansion and the unperturbed
      state coincides with the limiting setting where the multiplex layers are
      decoupled. The interaction between adjacent layers can seed the instability of a
      homogeneous fixed point, yielding self-organized patterns which are instead
      impeded in the limit of decoupled layers. Patterns on individual layers can also
      fade away due to cross-talking between layers. Analytical results are compared to
      direct simulations. 

PMID- 25375557
TI  - Zipf's law in city size from a resource utilization model.
AB  - We study a resource utilization scenario characterized by intrinsic fitness. To
      describe the growth and organization of different cities, we consider a model for
      resource utilization where many restaurants compete, as in a game, to attract
      customers using an iterative learning process. Results for the case of
      restaurants with uniform fitness are reported. When fitness is uniformly
      distributed, it gives rise to a Zipf law for the number of customers. We perform
      an exact calculation for the utilization fraction for the case when choices are
      made independent of fitness. A variant of the model is also introduced where the
      fitness can be treated as an ability to stay in the business. When a restaurant
      loses customers, its fitness is replaced by a random fitness. The steady state
      fitness distribution is characterized by a power law, while the distribution of
      the number of customers still follows the Zipf law, implying the robustness of
      the model. Our model serves as a paradigm for the emergence of Zipf law in city
      size distribution. 

PMID- 25375558
TI  - Continuum modeling of crowd turbulence.
AB  - With the growth in world population, the density of crowds in public places has
      been increasing steadily, leading to a higher incidence of crowd disasters at
      high densities. Recent research suggests that emergent chaotic behavior at high
      densities-known collectively as crowd turbulence-is to blame. Thus, a deeper
      understanding of crowd turbulence is needed to facilitate efforts to prevent and
      plan for chaotic conditions in high-density crowds. However, it has been noted
      that existing algorithms modeling collision avoidance cannot faithfully simulate
      crowd turbulence. We hypothesize that simulation of crowd turbulence requires
      modeling of both collision avoidance and frictional forces arising from
      pedestrian interactions. Accordingly, we propose a model for turbulent crowd
      simulation, which incorporates a model for interpersonal stress and acceleration
      constraints similar to real-world pedestrians. Our simulated results demonstrate
      a close correspondence with observed metrics for crowd turbulence as measured in
      known crowd disasters. 

PMID- 25375559
TI  - Mesoscopic analysis of online social networks: the role of negative ties.
AB  - A class of networks are those with both positive and negative links. In this
      manuscript, we studied the interplay between positive and negative ties on
      mesoscopic level of these networks, i.e., their community structure. A community
      is considered as a tightly interconnected group of actors; therefore, it does not
      borrow any assumption from balance theory and merely uses the well-known
      assumption in the community detection literature. We found that if one detects
      the communities based on only positive relations (by ignoring the negative ones),
      the majority of negative relations are already placed between the communities. In
      other words, negative ties do not have a major role in community formation of
      signed networks. Moreover, regarding the internal negative ties, we proved that
      most unbalanced communities are maximally balanced, and hence they cannot be
      partitioned into k nonempty sub-clusters with higher balancedness (k>=2).
      Furthermore, we showed that although the mediator triad ++- (hostile-mediator
      hostile) is underrepresented, it constitutes a considerable portion of triadic
      relations among communities. Hence, mediator triads should not be ignored by
      community detection and clustering algorithms. As a result, if one uses a
      clustering algorithm that operates merely based on social balance, mesoscopic
      structure of signed networks significantly remains hidden. 

PMID- 25375560
TI  - Modeling spatial patterns in the visual cortex.
AB  - We propose a model for the formation of patterns in the visual cortex. The
      dynamical units of the model are Kuramoto phase oscillators that interact through
      a complex network structure embedded in two dimensions. In this way the strength
      of the interactions takes into account the geographical distance between units.
      We show that for different parameters, clustered or striped patterns emerge.
      Using the structure factor as an order parameter we are able to quantitatively
      characterize these patterns and present a phase diagram. Finally, we show that
      the model is able to reproduce patterns with cardinal preference, as observed in
      ferrets. 

PMID- 25375561
TI  - Mixed solitons in a (2+1)-dimensional multicomponent long-wave-short-wave system.
AB  - We derive a (2+1)-dimensional multicomponent long-wave-short-wave resonance
      interaction (LSRI) system as the evolution equation for propagation of N
      dispersive waves in weak Kerr-type nonlinear medium in the small-amplitude limit.
      The mixed- (bright-dark) type soliton solutions of a particular (2+1)-dimensional
      multicomponent LSRI system, deduced from the general multicomponent higher
      dimensional LSRI system, are obtained by applying the Hirota's bilinearization
      method. Particularly, we show that the solitons in the LSRI system with two short
      wave components behave like scalar solitons. We point out that for an N-component
      LSRI system with N>3, if the bright solitons appear in at least two components,
      interesting collision behavior takes place, resulting in energy exchange among
      the bright solitons. However, the dark solitons undergo standard elastic
      collision accompanied by a position shift and a phase shift. Our analysis on the
      mixed bound solitons shows that the additional degree of freedom which arises due
      to the higher-dimensional nature of the system results in a wide range of
      parameters for which the soliton collision can take place. 

PMID- 25375562
TI  - Sound synchronization of bubble trains in a viscous fluid: experiment and
      modeling.
AB  - We investigate the dynamics of formation of air bubbles expelled from a nozzle
      immersed in a viscous fluid under the influence of sound waves. We have obtained
      bifurcation diagrams by measuring the time between successive bubbles, having the
      air flow (Q) as a parameter control for many values of the sound wave amplitude
      (A), the height (H) of the solution above the top of the nozzle, and three values
      of the sound frequency (fs). Our parameter spaces (Q,A) revealed a scenario for
      the onset of synchronization dominated by Arnold tongues (frequency locking)
      which gives place to chaotic phase synchronization for sufficiently large A. The
      experimental results were accurately reproduced by numerical simulations of a
      model combining a simple bubble growth model for the bubble train and a coupling
      term with the sound wave added to the equilibrium pressure.

PMID- 25375563
TI  - Solitary waves in a nonintegrable Fermi-Pasta-Ulam chain.
AB  - We present a family of exact solutions describing discrete solitary waves in a
      nonintegrable Fermi-Pasta-Ulam chain. The family is sufficiently rich to cover
      the whole spectrum of known behaviors from delocalized quasicontinuum waves
      moving with near-sonic velocities to highly localized anticontinuum excitations
      with only one particle moving at a time. 

PMID- 25375564
TI  - Time-delay effects on the aging transition in a population of coupled
      oscillators.
AB  - We investigate the influence of time-delayed coupling on the nature of the aging
      transition in a system of coupled oscillators that have a mix of active and
      inactive oscillators, where the aging transition is defined as the gradual loss
      of collective synchrony as the proportion of inactive oscillators is increased.
      We start from a simple model of two time-delay coupled Stuart-Landau oscillators
      that have identical frequencies but are located at different distances from the
      Hopf bifurcation point. A systematic numerical and analytic study delineates the
      dependence of the critical coupling strength (at which the system experiences
      total loss of synchrony) on time delay and the average distance of the system
      from the Hopf bifurcation point. We find that time delay can act to facilitate
      the aging transition by lowering the threshold coupling strength for amplitude
      death in the system. We then extend our study to larger systems of globally
      coupled active and inactive oscillators including an infinite system in the
      thermodynamic limit. Our model system and results can provide a useful paradigm
      for understanding the functional robustness of diverse physical and biological
      systems that are prone to aging transitions. 

PMID- 25375565
TI  - Hysteretic transitions in the Kuramoto model with inertia.
AB  - We report finite-size numerical investigations and mean-field analysis of a
      Kuramoto model with inertia for fully coupled and diluted systems. In particular,
      we examine, for a gaussian distribution of the frequencies, the transition from
      incoherence to coherence for increasingly large system size and inertia. For
      sufficiently large inertia the transition is hysteretic, and within the
      hysteretic region clusters of locked oscillators of various sizes and different
      levels of synchronization coexist. A modification of the mean-field theory
      developed by Tanaka, Lichtenberg, and Oishi [Physica D 100, 279 (1997)] allows us
      to derive the synchronization curve associated to each of these clusters. We have
      also investigated numerically the limits of existence of the coherent and of the
      incoherent solutions. The minimal coupling required to observe the coherent state
      is largely independent of the system size, and it saturates to a constant value
      already for moderately large inertia values. The incoherent state is observable
      up to a critical coupling whose value saturates for large inertia and for finite
      system sizes, while in the thermodinamic limit this critical value diverges
      proportionally to the mass. By increasing the inertia the transition becomes more
      complex, and the synchronization occurs via the emergence of clusters of whirling
      oscillators. The presence of these groups of coherently drifting oscillators
      induces oscillations in the order parameter. We have shown that the transition
      remains hysteretic even for randomly diluted networks up to a level of
      connectivity corresponding to a few links per oscillator. Finally, an application
      to the Italian high-voltage power grid is reported, which reveals the emergence
      of quasiperiodic oscillations in the order parameter due to the simultaneous
      presence of many competing whirling clusters. 

PMID- 25375566
TI  - Influence of intrapulse Raman scattering on stationary pulses in the presence of
      linear and nonlinear gain as well as spectral filtering.
AB  - We examine numerically the influence of intrapulse Raman scattering (IRS) on the
      stable stationary pulses in the presence of constant linear and nonlinear gain as
      well as spectral filtering. Numerical results show that the small change of the
      value of the parameter describing IRS leads to qualitatively different behavior
      of the evolution of pulse amplitudes. We prove that the strong dependence of the
      pulse dynamics on the parameter describing IRS is related to the existence of the
      Poincare-Andronov-Hopf bifurcation and the appearance of the unstable limit
      cycle. 

PMID- 25375567
TI  - Impact of heterogeneous delays on cluster synchronization.
AB  - We investigate cluster synchronization in coupled map networks in the presence of
      heterogeneous delays. We find that while the parity of heterogeneous delays plays
      a crucial role in determining the mechanism of cluster formation, the cluster
      synchronizability of the network gets affected by the amount of heterogeneity. In
      addition, heterogeneity in delays induces a rich cluster pattern as compared to
      homogeneous delays. The complete bipartite network stands as an extreme example
      of this richness, where robust ideal driven clusters observed for the undelayed
      and homogeneously delayed cases dismantle, yielding versatile cluster patterns as
      heterogeneity in the delay is introduced. We provide arguments behind this
      behavior using a Lyapunov function analysis. Furthermore, the interplay between
      the number of connections in the network and the amount of heterogeneity plays an
      important role in deciding the cluster formation. 

PMID- 25375568
TI  - Network dynamics for optimal compressive-sensing input-signal recovery.
AB  - By using compressive sensing (CS) theory, a broad class of static signals can be
      reconstructed through a sequence of very few measurements in the framework of a
      linear system. For networks with nonlinear and time-evolving dynamics, is it
      similarly possible to recover an unknown input signal from only a small number of
      network output measurements? We address this question for pulse-coupled networks
      and investigate the network dynamics necessary for successful input signal
      recovery. Determining the specific network characteristics that correspond to a
      minimal input reconstruction error, we are able to achieve high-quality signal
      reconstructions with few measurements of network output. Using various measures
      to characterize dynamical properties of network output, we determine that
      networks with highly variable and aperiodic output can successfully encode
      network input information with high fidelity and achieve the most accurate CS
      input reconstructions. For time-varying inputs, we also find that high-quality
      reconstructions are achievable by measuring network output over a relatively
      short time window. Even when network inputs change with time, the same optimal
      choice of network characteristics and corresponding dynamics apply as in the case
      of static inputs. 

PMID- 25375569
TI  - Dynamical scaling of fragment distribution in drying paste.
AB  - Crack patterns of drying paste and their statistical properties are investigated
      through smoothed particle hydrodynamics, which is one method for solving
      continuum equations in the Lagrangian description. In addition to reproducing a
      realistic crack pattern, we also find that the average area of a fragment decays
      inversely with time in the case of linearly increasing desiccation stress. We
      find that the distribution can be scaled with the average area of the fragment
      over the corresponding time, even though the distribution function of the
      fragment area changes the functional form during evolution. 

PMID- 25375570
TI  - Influence of self-steepening and intrapulse Raman scattering on modulation
      instability in oppositely directed coupler.
AB  - We investigate the modulation instability in oppositely directed coupler in the
      presence of higher-order effects. Using linear stability analysis, we obtain an
      expression for instability gain. Special attention is paid to find out the
      influence of self-steepening effect and intrapulse Raman scattering on modulation
      instability. The study shows that in normal dispersion, regime instability gain
      exists even if perturbation frequency (Omega) is zero. But the instability gain
      at Omega=0 is zero, when the dispersion is anomalous. Moreover, self-steepening
      effect and intrapulse Raman scattering form new instability regions and, hence,
      provide a new way to generate solitons or ultrashort pulses. Further, efficient
      control of modulation instability by adjusting self-steepening effect and
      intrapulse Raman scattering also successfully demonstrated. 

PMID- 25375571
TI  - Two-cluster solutions in an ensemble of generic limit-cycle oscillators with
      periodic self-forcing via the mean-field.
AB  - We study two-cluster solutions of an ensemble of generic limit-cycle oscillators
      in the vicinity of a Hopf bifurcation, i.e., Stuart-Landau oscillators, with a
      nonlinear global coupling. This coupling leads to conserved mean-field
      oscillations acting back on the individual oscillators as a forcing. A reduction
      to two effective equations makes a linear stability analysis of the cluster
      solutions possible. These equations exhibit a pi-rotational symmetry, leading to
      a complex bifurcation structure and a wide variety of solutions. In fact, the
      principal bifurcation structure resembles that of a 2:1 resonance tongue, while
      inside the tongue we observe an 1:1 entrainment. 

PMID- 25375572
TI  - Vector rogue waves and dark-bright boomeronic solitons in autonomous and
      nonautonomous settings.
AB  - In this work we consider the dynamics of vector rogue waves and dark-bright
      solitons in two-component nonlinear Schrodinger equations with various physically
      motivated time-dependent nonlinearity coefficients, as well as spatiotemporally
      dependent potentials. A similarity transformation is utilized to convert the
      system into the integrable Manakov system and subsequently the vector rogue and
      dark-bright boomeronlike soliton solutions of the latter are converted back into
      ones of the original nonautonomous model. Using direct numerical simulations we
      find that, in most cases, the rogue wave formation is rapidly followed by a
      modulational instability that leads to the emergence of an expanding soliton
      train. Scenarios different than this generic phenomenology are also reported. 

PMID- 25375573
TI  - Symmetries and transport in site-dependent driven quantum lattices.
AB  - We explore the quantum dynamics of particles in a spatiotemporally driven
      lattice. A powerful numerical scheme is developed which provides us with the
      Floquet modes and thus enables a stroboscopic propagation of arbitrary initial
      states. A detailed symmetry analysis represents the cornerstone for an intricate
      manipulation of the Floquet spectrum. Specifically, we show how exact crossings
      can be converted into avoided ones, while the widths of these resulting avoided
      crossings can be engineered by adjusting parameters of the local driving.
      Asymptotic currents are shown to be controllable over a certain parameter range. 

PMID- 25375575
TI  - Universal Braess paradox in open quantum dots.
AB  - We present analytical and numerical results that demonstrate the presence of the
      Braess paradox in chaotic quantum dots. The paradox that we identify, originally
      perceived in classical networks, shows that the addition of more capacity to the
      network can suppress the current flow in the universal regime. We investigate the
      weak localization term, showing that it presents the paradox encoded in a
      saturation minimum of the conductance, under the presence of hyperflow in the
      external leads. In addition, we demonstrate that the weak localization suffers a
      transition signal depending on the overcapacity lead and presents an echo on the
      magnetic crossover before going to zero due to the full time-reversal symmetry
      breaking. We also show that the quantum interference contribution can dominate
      the Ohm term in the presence of constrictions and that the corresponding Fano
      factor engenders an anomalous behavior. 

PMID- 25375574
TI  - Controlling cluster synchronization by adapting the topology.
AB  - We suggest an adaptive control scheme for the control of in-phase and cluster
      synchronization in delay-coupled networks. Based on the speed-gradient method,
      our scheme adapts the topology of a network such that the target state is
      realized. It is robust towards different initial conditions as well as changes in
      the coupling parameters. The emerging topology is characterized by a delicate
      interplay of excitatory and inhibitory links leading to the stabilization of the
      desired cluster state. As a crucial parameter determining this interplay we
      identify the delay time. Furthermore, we show how to construct networks such that
      they exhibit not only a given cluster state but also with a given oscillation
      frequency. We apply our method to coupled Stuart-Landau oscillators, a
      paradigmatic normal form that naturally arises in an expansion of systems close
      to a Hopf bifurcation. The successful and robust control of this generic model
      opens up possible applications in a wide range of systems in physics, chemistry,
      technology, and life science. 

PMID- 25375576
TI  - Kink topology control by high-frequency external forces in nonlinear Klein-Gordon
      models.
AB  - A method of averaging is applied to study the dynamics of a kink in the damped
      double sine-Gordon equation driven by both external (nonparametric) and
      parametric periodic forces at high frequencies. This theoretical approach leads
      to the study of a double sine-Gordon equation with an effective potential and an
      effective additive force. Direct numerical simulations show how the appearance of
      two connected pi kinks and of an individual pi kink can be controlled via the
      frequency. An anomalous negative mobility phenomenon is also predicted by theory
      and confirmed by simulations of the original equation. 

PMID- 25375577
TI  - Number of first-passage times as a measurement of information for weakly chaotic
      systems.
AB  - We consider a general class of maps of the interval having Lyapunov
      subexponential instability |deltaxt|~|deltax0|exp[Lambdat(x0)zeta(t)], where
      zeta(t) grows sublinearly as t->infinity. We outline here a scheme [J. Stat.
      Phys. 154, 988 (2014)] whereby the choice of a characteristic function
      automatically defines the map equation and corresponding growth rate zeta(t).
      This matching approach is based on the infinite measure property of such systems.
      We show that the average information that is necessary to record without
      ambiguity a trajectory of the system tends to <Lambda>zeta(t), suitably extending
      the Kolmogorov-Sinai entropy and Pesin's identity. For such systems, information
      behaves like a random variable for random initial conditions, its statistics
      obeying a universal Mittag-Leffler law. We show that, for individual
      trajectories, information can be accurately inferred by the number of first
      passage times through a given turbulent phase-space cell. This enables us to
      calculate far more efficiently Lyapunov exponents for such systems. Lastly, we
      also show that the usual renewal description of jumps to the turbulent cell,
      usually employed in the literature, does not provide the real number of entrances
      there. Our results are supported by exhaustive numerical simulations.

PMID- 25375578
TI  - Microscopic mechanism for self-organized quasiperiodicity in random networks of
      nonlinear oscillators.
AB  - Self-organized quasiperiodicity is one of the most puzzling dynamical phases
      observed in systems of nonlinear coupled oscillators. The single dynamical units
      are not locked to the periodic mean field they produce, but they still feature a
      coherent behavior, through an unexplained complex form of correlation. We
      consider a class of leaky integrate-and-fire oscillators on random sparse and
      massive networks with dynamical synapses, featuring self-organized
      quasiperiodicity, and we show how complex collective oscillations arise from
      constructive interference of microscopic dynamics. In particular, we find a
      simple quantitative relationship between two relevant microscopic dynamical time
      scales and the macroscopic time scale of the global signal. We show that the
      proposed relation is a general property of collective oscillations, common to all
      the partially synchronous dynamical phases analyzed. We argue that an analogous
      mechanism could be at the origin of similar network dynamics. 

PMID- 25375579
TI  - Entropy of weighted recurrence plots.
AB  - The Shannon entropy of a time series is a standard measure to assess the
      complexity of a dynamical process and can be used to quantify transitions between
      different dynamical regimes. An alternative way of quantifying complexity is
      based on state recurrences, such as those available in recurrence quantification
      analysis. Although varying definitions for recurrence-based entropies have been
      suggested so far, for some cases they reveal inconsistent results. Here we
      suggest a method based on weighted recurrence plots and show that the associated
      Shannon entropy is positively correlated with the largest Lyapunov exponent. We
      demonstrate the potential on a prototypical example as well as on experimental
      data of a chemical experiment. 

PMID- 25375580
TI  - Self-organizing patterns in an evolutionary rock-paper-scissors game for
      stochastic synchronized strategy updates.
AB  - We study a spatial evolutionary rock-paper-scissors game with synchronized
      strategy updating. Players gain their payoff from games with their four neighbors
      on a square lattice and can update their strategies simultaneously according to
      the logit rule, which is the noisy version of the best-response dynamics. For the
      synchronized strategy update two types of global oscillations (with an ordered
      strategy arrangement and periods of three and six generations) can occur in this
      system in the zero noise limit. At low noise values, all nine oscillating phases
      are present in the system by forming a self-organizing spatial pattern due to the
      comprising invasion and speciation processes along the interfaces separating the
      different domains. 

PMID- 25375581
TI  - Instability dynamics and breather formation in a horizontally shaken pendulum
      chain.
AB  - Inspired by the experimental results of Cuevas et al. [Phys. Rev. Lett. 102,
      224101 (2009)], we consider theoretically the behavior of a chain of planar rigid
      pendulums suspended in a uniform gravitational field and subjected to a
      horizontal periodic driving force applied to the pendulum pivots. We characterize
      the motion of a single pendulum, finding bistability near the fundamental
      resonance and near the period-3 subharmonic resonance. We examine the development
      of modulational instability in a driven pendulum chain and find both a critical
      chain length and a critical frequency for the appearance of the instability. We
      study the breather solutions and show their connection to the single-pendulum
      dynamics and extend our analysis to consider multifrequency breathers connected
      to the period-3 periodic solution, showing also the possibility of stability in
      these breather states. Finally we examine the problem of breather generation and
      demonstrate a robust scheme for generation of on-site and off-site breathers. 

PMID- 25375582
TI  - Collective coordinates theory for discrete soliton ratchets in the sine-Gordon
      model.
AB  - A collective coordinate theory is developed for soliton ratchets in the damped
      discrete sine-Gordon model driven by a biharmonic force. An ansatz with two
      collective coordinates, namely the center and the width of the soliton, is
      assumed as an approximated solution of the discrete nonlinear equation. The
      dynamical equations of these two collective coordinates, obtained by means of the
      generalized travelling wave method, explain the mechanism underlying the soliton
      ratchet and capture qualitatively all the main features of this phenomenon. The
      numerical simulation of these equations accounts for the existence of a nonzero
      depinning threshold, the nonsinusoidal behavior of the average velocity as a
      function of the relative phase between the harmonics of the driver, the
      nonmonotonic dependence of the average velocity on the damping, and the existence
      of nontransporting regimes beyond the depinning threshold. In particular, it
      provides a good description of the intriguing and complex pattern of subspaces
      corresponding to different dynamical regimes in parameter space. 

PMID- 25375583
TI  - Cross-frequency synchronization of oscillators with time-delayed coupling.
AB  - We carry out theoretical and experimental studies of cross-frequency
      synchronization of two pulse oscillators with time-delayed coupling. In the
      theoretical part of the paper we utilize the concept of phase resetting curves
      and analyze the system dynamics in the case of weak coupling. We construct a
      Poincare map and obtain the synchronization zones in the parameter space for m:n
      synchronization. To challenge the theoretical results we designed an electronic
      circuit implementing the coupled oscillators and studied its dynamics
      experimentally. We show that the developed theory predicts dynamical properties
      of the realistic system, including location of the synchronization zones and
      bifurcations inside them. 

PMID- 25375584
TI  - Vibrational higher-order resonances in an overdamped bistable system with
      biharmonic excitation.
AB  - Experimental evidence of vibrational higher-order resonances in a bistable
      vertical-cavity surface-emitting laser driven by two harmonic signals with very
      different frequencies is reported. The phenomenon shows up in a parameter space
      (the dc current, the amplitude of the high-frequency signal) as well-defined
      structures with multiple local maxima at higher harmonics of the low-frequency
      signal. Such structures appear due to a strong suppression of higher harmonics
      for certain values of the high-frequency amplitude and the dc current. Complexity
      of the structures and the total number of the local maxima depend on the harmonic
      order k. The behavior of nonlinear distortion factor is also studied. The
      experimental results are in a good agreement with the numerical results which
      were obtained in the model of the bistable overdamped oscillator with biharmonic
      excitation. 

PMID- 25375585
TI  - Interface and vortex motion in the two-component complex dissipative Ginzburg
      Landau equation in two-dimensional space.
AB  - We study interface and vortex motion in the two-component dissipative Ginzburg
      Landau equation in two-dimensional space. We consider cases where the whole
      system is divided into several domains, and we assume that these domains are
      separated by interfaces and each domain contains quantized vortices. The
      equations for interface and vortex motion will be derived by means of a
      variational approach by Kawasaki. These equations indicate that, along an
      interface, the phase gradient fields of the complex order parameters is parallel
      to the interface. They also indicate that the interface motion is driven by the
      curvature and the phase gradient fields along the interface, and vortex motion is
      driven by the phase gradient field around the vortex. With respect to the static
      interactions between defects, we find an analogy between quantized vortices in a
      domain and electric charges in a vacuum domain surrounded by a metallic object in
      electrostatic. This analogy indicates that there is an attractive interaction
      between an interface and a quantized vortex with any charge. We also discuss
      several examples of interface and vortex motion. 

PMID- 25375586
TI  - Locking of periodic patterns in Cahn-Hilliard models for Langmuir-Blodgett
      transfer.
AB  - The influence of a periodic spatial forcing on the pattern formation in a
      generalized Cahn-Hilliard model describing Langmuir-Blodgett transfer is studied.
      The occurring locking effects enable a control mechanism for the pattern
      formation process. In the one-dimensional case the parameter range in which
      patterns are created is increased and the patterns' properties can be adjusted in
      a broader range. In two dimensions, one-dimensional stripe patterns can be
      destabilized, giving rise to a multitude of complex two-dimensional structures,
      including oblique and lattice patterns. 

PMID- 25375587
TI  - Collision dynamics of traveling bands in systems of deformable self-propelled
      particles.
AB  - We study the soliton-like character of traveling bands in systems of interacting
      deformable self-propelled particles in two dimensions. The collision dynamics of
      the model in which migration velocity increases with increasing local density is
      investigated numerically by changing the relaxation rate of deformations. The
      bands are unstable upon head-on collisions for larger relaxation rates. This
      clearly indicates that deformability plays a crucial role of the soliton-like
      behavior. 

PMID- 25375588
TI  - Topologies of velocity-field stagnation points generated by a single pair of
      magnets in free-surface electromagnetic experiments.
AB  - The velocity fields generated by a static pair of magnets in free-surface
      electromagnetically forced flows are analyzed for different magnet attitudes,
      ionic currents, and brine depths. A wide range of laminar velocity fields is
      obtained despite the forcing simplicity. The velocity fields are classified
      according to their temporal mean flow topology, which strongly depends on the
      forcing geometry but barely on its strength, even through the bifurcation to
      unsteady regimes. The mean flow topology possesses a major influence on the
      critical Reynolds number Rec under which the steady velocity fields remain
      stable. The qualitative comparison of the dependence of Rec on the topology is in
      agreement with previous works. The unsteady configurations evidence the advection
      of smaller flow structures by the largest scales, commonly known as "sweeping."

PMID- 25375589
TI  - Locomotion of microorganisms near a no-slip boundary in a viscoelastic fluid.
AB  - Locomotion of microorganisms plays a vital role in most of their biological
      processes. In many of these processes, microorganisms are exposed to complex
      fluids while swimming in confined domains, such as spermatozoa in mucus of
      mammalian reproduction tracts or bacteria in extracellular polymeric matrices
      during biofilm formation. Thus, it is important to understand the kinematics of
      propulsion in a viscoelastic fluid near a no-slip boundary. We use a squirmer
      model with a time-reversible body motion to analytically investigate the swimming
      kinematics in an Oldroyd-B fluid near a wall. Analysis of the time-averaged
      motion of the swimmer shows that both pullers and pushers in a viscoelastic fluid
      swim towards the no-slip boundary if they are initially located within a small
      domain of "attraction" in the vicinity of the wall. In contrast, neutral swimmers
      always move towards the wall regardless of their initial distance from the wall.
      Outside the domain of attraction, pullers and pushers are both repelled from the
      no-slip boundary. Time-averaged locomotion is most pronounced at a Deborah number
      of unity. We examine the swimming trajectories of different types of swimmers as
      a function of their initial orientation and distance from the no-slip boundary. 

PMID- 25375590
TI  - Wave-vortex mode coupling in neutrally stable baroclinic flows.
AB  - Rotating stratified flows in thermal wind balance are at the center of
      geophysical fluid dynamics. Recently, endeavors were put on studying the linear
      response of such flows to potential vorticity perturbations. It has been shown
      that the initial potential vorticity (PV) distribution is fundamental and is
      responsible for important transient growth of the perturbation and gravity-wave
      generation. Using Pfeiffer's theorem [J. Differ. Equat. 11, 145 (1972)], we give
      the mathematical demonstration of the stability of asymmetric perturbations k1?0
      of a uniform, unbounded flow in thermal wind balance. Incidentally, we prove that
      both the wave mode (that corresponds to a vanishing PV) and the vortex mode
      (corresponding to a nonzero PV) are stable. The emphasis is put on the nontrivial
      behavior of inertia-gravity waves (IGWs) when deformed by a background shear. In
      particular, we show that in the linear limit, sheared inertia-gravity waves
      asymptotically oscillate at the inertial waves frequency, but their amplitude is
      sensitive to shear, stratification, and rotation. Last, we study the development
      of the IGWs dynamics considering isotropic initial conditions. Computations
      indicate that both the vortex mode and the wave mode generate IGWs, but the
      energy of the IGWs generated by the vortex mode is more important than the energy
      of the IGWs generated by the wave mode. It is also found that, at large times,
      the energy of the IGWs generated by the vortex mode increases as the ratio kv/kh
      (initial vertical wavenumber over horizontal wavenumber) increases (like
      kv(2)/kh(2)), while the energy of the IGWs generated by the wave mode oscillates
      in function of kv/kh.

PMID- 25375591
TI  - Instability of viscous flow over a deformable two-layered gel: experiments and
      theory.
AB  - The instability of the flow of a viscous fluid past a soft, two-layered gel is
      probed using experiments, and the observations are compared with results from a
      linear stability analysis. The experimental system consists of the rotating top
      plate of a rheometer and its stationary bottom plate on which the two-layer gel
      is placed. When the flow between the top plate and the two-layer gel is
      viscometric (i.e., laminar), the viscosity obtained from the rheometer is a
      measure of the material property of the fluid. However, after a critical shear
      stress, there is a sudden increase in apparent viscosity, indicating that the
      flow has undergone an instability due to the deformable nature of the two-layer
      gel. Experiments are carried out to quantify how the critical value of fluid
      shear stress required to destabilize the flow varies as a function of ratio of
      solid to fluid layer thickness, and the ratio of the shear moduli of the two
      gels. A linear stability analysis is carried out for plane Couette flow of a
      Newtonian fluid past the two-layered gel, by assuming the two solid layers to be
      elastic neo-Hookean materials. In order to compare the experimental and
      theoretical results, the effective shear modulus (Geff, defined by
      H/Geff=H1/G1+H2/G2) of the two-layer gel is found to be useful, where H=H1+H2.
      Here, Hi and Gi (i=1,2), respectively, denote the thickness and shear modulus of
      each layer. Results for the nondimensional parameter Gammaeff=etaV/(dGeff) (V is
      the velocity of the top plate; eta is fluid viscosity, d is the fluid thickness)
      as a function of solid to fluid thickness H/d obtained from the stability
      analysis agree well with experimental observations, without any fitting
      parameters. In general, we find that the flow is more unstable if the softer gel
      is adjacent to the fluid flow compared to the case when it is not. This suggests
      that the instability is more interfacial in nature and is crucially dependent on
      the relative placement of the two layers, and not just on the effective modulus
      of the two-layer gel. We further show that the theoretical and experimental data
      for two-layer gels can be suitably collapsed onto the results obtained for a
      single-gel layer.

PMID- 25375592
TI  - Mechanisms of particle clustering in Gaussian and non-Gaussian synthetic
      turbulence.
AB  - We use synthetic turbulence simulations to study how inertial particles cluster
      in a turbulent flow, for a wide range of Stokes numbers. Two different types of
      synthetic turbulence are used: one Gaussian, where the time evolution of the
      velocity field is a simple phase shift, and one non-Gaussian, where convection is
      used to evolve the velocity field in time. In both flow types we observe
      significant particle clustering over a wide range of scales and Stokes numbers.
      The clustering found at low Stokes numbers can be attributed to the vortex
      centrifuge effect, where heavy particles are expelled from regions dominated by
      vorticity. This mechanism is much more effective in the non-Gaussian turbulence,
      because local flow structures are convected with the particles. The preferential
      sampling of regions with low vorticity is almost negligible in the Gaussian
      turbulence. At higher Stokes numbers, caustics are formed in a very similar
      manner in both Gaussian and non-Gaussian synthetic turbulence. In non-Gaussian
      turbulence, heavy particles cluster in regions of low fluid kinetic energy, while
      the opposite is true in Gaussian turbulence. Our results show that synthetic
      simulations cannot correctly predict how the particle clustering correlates with
      local fluid flow properties, without including convection. 

PMID- 25375593
TI  - Class of periodic and quasiperiodic trajectories of particles settling under
      gravity in a viscous fluid.
AB  - We investigate regular configurations of a small number of non-Brownian particles
      settling under gravity in a viscous fluid. The particles do not touch each other
      and can move relative to each other. The dynamics is analyzed in the point
      particle approximation. A family of regular configurations is found with periodic
      oscillations of all the settling particles. The oscillations are shown to be
      robust under some out-of-phase rearrangements of the particles. In the presence
      of an additional particle above such a regular configuration, the particle
      periodic trajectories are horizontally repelled from the symmetry axis, and
      flattened vertically. The results are used to propose a mechanism of how a
      spherical cloud, made of a large number of particles distributed at random,
      evolves and destabilizes. 

PMID- 25375594
TI  - Electroviscous resistance of nanofluidic bends.
AB  - Analysis tools that quantify the pressure and potential changes occurring over
      pressure-driven electrokinetic device elements are necessary for the design of
      optimal laboratory-on-a-chip devices. In this study, the resistance of a
      nanofluidic silica channel with negatively charged walls containing a 90^{?} bend
      to the electroviscous flow of a potassium chloride salt solution is quantified in
      terms of two equivalent lengths using numerical analysis. One equivalent length
      is based on the excess pressure drop and the other on the excess potential rise.
      Over the entire range of simulations conducted, these equivalent lengths are
      relatively independent of salt concentration, flow velocity, channel size, and
      surface charge, remaining within the approximate ranges of 1.3-1.5 for the
      pressure equivalent length and 0.8-1.05 for the potential equivalent length. 

PMID- 25375595
TI  - Lateral migration of a spherical capsule near a plane wall in Stokes flow.
AB  - Lateral migration is the motion of a particle perpendicular to the direction of
      the surrounding flow. One of the factors leading to the lateral migration of a
      deformable particle in Stokes flow is the presence of a nearby wall. We
      numerically investigate the lateral migration of a capsule in a near-wall simple
      shear flow using a boundary integral method coupled with a finite element method.
      We find that asymmetrical deformation of the capsule induced by the wall is
      correlated with a reduction in the lift velocity relative to the lift velocity
      predicted by a far-field analytical solution. A combination of this asymmetrical
      deformation, which decreases the lift velocity, and an increase in the value of
      the capsule stresslet near the wall, which works to increase the lift velocity,
      leads to a migration velocity that is nearly independent of capillary number and
      membrane constitutive law at large deformation near the wall. 

PMID- 25375596
TI  - Magnetic field reversals and long-time memory in conducting flows.
AB  - Employing a simple ideal magnetohydrodynamic model in spherical geometry, we show
      that the presence of either rotation or finite magnetic helicity is sufficient to
      induce dynamical reversals of the magnetic dipole moment. The statistical
      character of the model is similar to that of terrestrial magnetic field
      reversals, with the similarity being stronger when rotation is present. The
      connection between long-time correlations, 1/f noise, and statistics of reversals
      is supported, consistent with earlier suggestions. 

PMID- 25375597
TI  - Filling of charged cylindrical capillaries.
AB  - We provide an analytical model to describe the filling dynamics of horizontal
      cylindrical capillaries having charged walls. The presence of surface charge
      leads to two distinct effects: It leads to a retarding electrical force on the
      liquid column and also causes a reduced viscous drag force because of decreased
      velocity gradients at the wall. Both these effects essentially stem from the
      spontaneous formation of an electric double layer (EDL) and the resulting
      streaming potential caused by the net capillary-flow-driven advection of ionic
      species within the EDL. Our results demonstrate that filling of charged
      capillaries also exhibits the well-known linear and Washburn regimes witnessed
      for uncharged capillaries, although the filling rate is always lower than that of
      the uncharged capillary. We attribute this to a competitive success of the
      lowering of the driving forces (because of electroviscous effects), in comparison
      to the effect of weaker drag forces. We further reveal that the time at which the
      transition between the linear and the Washburn regime occurs may become
      significantly altered with the introduction of surface charges, thereby altering
      the resultant capillary dynamics in a rather intricate manner. 

PMID- 25375598
TI  - Local dissipation scales in two-dimensional Rayleigh-Taylor turbulence.
AB  - We examine the distribution of the local dissipation scale eta, Q(eta), and its
      temporal evolution in two-dimensional (2D) Rayleigh-Taylor (RT) turbulence using
      direct numerical simulations at small Atwood number and unit Prandtl number.
      Within the self-similarity regime of the mixing zone evolution, distributions of
      eta at small scales are found to be insensitive to the large-scale anisotropy of
      the system and independent of position and of the temporal evolution of the
      mixing zone. Our results further reveal that the present measured Q(eta) agrees
      with those previously observed in homogeneous isotropic turbulence and in
      turbulent pipe flows, at least for the smallest scales around the classical
      Kolmogorov dissipation scale. However, the RT case seems to show a different
      trend from the other two cases for large scales, which may attributed to the
      absence of the inertial-range intermittency for the velocity field in 2D RT
      turbulence. 

PMID- 25375599
TI  - External front instabilities induced by a shocked particle ring.
AB  - The dispersion of a cylindrical particle ring by a blast or shock wave induces
      the formation of coherent structures which take the form of particle jets. A
      blast wave, issuing from the discharge of a planar shock wave at the exit of a
      conventional shock tube, is generated in the center of a granular medium ring
      initially confined inside a Hele-Shaw cell. With the present experimental setup,
      under impulsive acceleration, a solid particle-jet formation is observed in a
      quasi-two-dimensional configuration. The aim of the present investigation is to
      observe in detail the formation of very thin perturbations created around the
      external surface of the dispersed particle layer. By means of fast flow
      visualization with an appropriate recording window, we focus solely on the first
      instants during which the external particle ring becomes unstable. We find that
      the critical area of the destabilization of the external ring surface is constant
      regardless of the acceleration of the initial layer. Moreover, we observe in
      detail the external front perturbation wavelength, rendered dimensionless by the
      initial ring perimeter, and follow its evolution with the initial particle layer
      acceleration. We report this quantity to be constant regardless of the evolution
      of the initial particle layer acceleration. Finally, we can reasonably assert
      that external front perturbations depend solely on the material of the particles.

PMID- 25375600
TI  - Active control of vortex shedding: an explanation of the gain window.
AB  - This paper explains the gain window phenomenon seen in early experimental and
      computational studies on active, closed-loop control of vortex shedding, whereby
      shedding is completely suppressed only if the feedback gain lies within some
      narrow window of stabilizing gains. Using two-dimensional direct numerical
      simulations and reduced-order modeling techniques, a low-order, linear model of
      the cylinder wake is formed at a Reynolds number of 60. This model is used to
      reproduce and to explain the gain window seen in previous studies. It is shown
      that the gain window is not caused by the destabilization of a higher mode but
      rather is determined entirely by the behavior of the open-loop unstable mode
      under the action of the closed-loop controller. It is demonstrated that the time
      taken for actuated fluid to convect to the sensor location plays an important
      part in explaining this gain window. A similar analysis at a higher Reynolds
      number of 80 reveals that the wake remains unstable for all choices of the
      feedback gain. The study illustrates the limitations of closed-loop suppression
      of vortex shedding when a very simple control strategy is used. 

PMID- 25375601
TI  - Deformation and breakup of a liquid droplet past a solid circular cylinder: a
      lattice Boltzmann study.
AB  - In this paper, we present a numerical study on the deformation and breakup
      behavior of liquid droplet past a solid circular cylinder by using an improved
      interparticle-potential lattice Boltzmann method. The effects of the eccentric
      ratio beta, viscosity ratio lambda between the droplet and the surrounding fluid,
      surface wettability, and Bond number (Bo) on the dynamic behavior of the liquid
      droplet are considered. The parameter beta represents the degree that the solid
      cylinder deviates from the center line, and Bo is the ratio between the inertial
      force and capillary force. Numerical results show that there are two typical
      patterns, i.e., breakup and no breakup, which are greatly influenced by the
      aforementioned parameters. When beta increases to a critical value betac, the
      droplet can pass the circular cylinder without a breakup, otherwise, the breakup
      phenomenon occurs. The critical eccentric ratio betac increases significantly
      with increasing Bo for case with lambda>1, while for the case with lambda<1, the
      viscosity effects on the betac is not obvious when Bo is large. For the breakup
      case, the amount of deposited liquid on the tip of the circular cylinder is
      almost unaffected by beta. In addition, the results also show that the viscosity
      ratio and wettability affect the deformation and breakup process of the droplet.
      For case with lambda<1, the viscosity ratio plays a minor role in the thickness
      variations of the deposited liquid, which decreases to a nonzero constant
      eventually; while for lambda>1, the increase of the viscosity ratio significantly
      accelerates the decrease of the deposited liquid, and finally no fluid deposits
      on the cylinder. In term of the wettability, there occurs continuous gas phase
      trapped by the wetting droplet, but this does not happen for nonwetting droplet.
      Besides, for lambda<1, the time required to pass the cylinder (tp) decreases
      monotonically with decreasing contact angle, while a nonmonotonic decrease
      appears for lambda>1. It is also found that tp decreases monotonically with
      increasing Bo and is less sensitive to lambda at a large Bo.

PMID- 25375602
TI  - Numerical study of thermoviscous effects in ultrasound-induced acoustic streaming
      in microchannels.
AB  - We present a numerical study of thermoviscous effects on the acoustic streaming
      flow generated by an ultrasound standing-wave resonance in a long straight
      microfluidic channel containing a Newtonian fluid. These effects enter primarily
      through the temperature and density dependence of the fluid viscosity. The
      resulting magnitude of the streaming flow is calculated and characterized
      numerically, and we find that even for thin acoustic boundary layers, the channel
      height affects the magnitude of the streaming flow. For the special case of a
      sufficiently large channel height, we have successfully validated our numerics
      with analytical results from 2011 by Rednikov and Sadhal for a single planar
      wall. We analyzed the time-averaged energy transport in the system and the time
      averaged second-order temperature perturbation of the fluid. Finally, we have
      made three main changes in our previously published numerical scheme to improve
      the numerical performance: (i) The time-averaged products of first-order
      variables in the time-averaged second-order equations have been recast as flux
      densities instead of as body forces. (ii) The order of the finite-element basis
      functions has been increased in an optimal manner. (iii) Based on the
      International Association for the Properties of Water and Steam (IAPWS 1995,
      2008, and 2011), we provide accurate polynomial fits in temperature for all
      relevant thermodynamic and transport parameters of water in the temperature range
      from 10 to 50  degrees C.

PMID- 25375603
TI  - Gas cushion model and hydrodynamic boundary conditions for superhydrophobic
      textures.
AB  - Superhydrophobic Cassie textures with trapped gas bubbles reduce drag, by
      generating large effective slip, which is important for a variety of applications
      that involve a manipulation of liquids at the small scale. Here we discuss how
      the dissipation in the gas phase of textures modifies their friction properties.
      We propose an operator method, which allows us to map the flow in the gas
      subphase to a local slip boundary condition at the liquid-gas interface. The
      determined uniquely local slip length depends on the viscosity contrast and
      underlying topography, and can be immediately used to evaluate an effective slip
      of the texture. Besides superlubricating Cassie surfaces, our approach is valid
      for rough surfaces impregnated by a low-viscosity "lubricant," and even for
      Wenzel textures, where a liquid follows the surface relief. These results provide
      a framework for the rational design of textured surfaces for numerous
      applications. 

PMID- 25375604
TI  - Magnetic induction and diffusion mechanisms in a liquid sodium spherical Couette
      experiment.
AB  - We present a reconstruction of the mean axisymmetric azimuthal and meridional
      flows in the Derviche Tourneur Sodium installation in Grenoble liquid sodium
      experiment. The experimental device sets a spherical Couette flow enclosed
      between two concentric spherical shells where the inner sphere holds a strong
      dipolar magnet, which acts as a magnetic propeller when rotated. Measurements of
      the mean velocity, mean induced magnetic field, and mean electric potentials have
      been acquired inside and outside the fluid for an inner sphere rotation rate of 9
      Hz (Rm?28). Using the induction equation to relate all measured quantities to the
      mean flow, we develop a nonlinear least-squares inversion procedure to
      reconstruct a fully coherent solution of the mean velocity field. We also include
      in our inversion the response of the fluid layer to the nonaxisymmetric time
      dependent magnetic field that results from deviations of the imposed magnetic
      field from an axial dipole. The mean azimuthal velocity field we obtain shows
      superrotation in an inner region close to the inner sphere where the Lorentz
      force dominates, which contrasts with an outer geostrophic region governed by the
      Coriolis force, but where the magnetic torque remains the driver. The meridional
      circulation is strongly hindered by the presence of both the Lorentz and the
      Coriolis forces. Nevertheless, it contributes to a significant part of the
      induced magnetic energy. Our approach sets the scene for evaluating the
      contribution of velocity and magnetic fluctuations to the mean magnetic field, a
      key question for dynamo mechanisms. 

PMID- 25375605
TI  - Reynolds number of transition and self-organized criticality of strong
      turbulence.
AB  - A turbulent flow is characterized by velocity fluctuations excited in an
      extremely broad interval of wave numbers k>Lambdaf, where Lambdaf is a relatively
      small set of the wave vectors where energy is pumped into fluid by external
      forces. Iterative averaging over small-scale velocity fluctuations from the
      interval Lambdaf<k<=Lambda0, where eta=2pi/Lambda0 is the dissipation scale,
      leads to an infinite number of "relevant" scale-dependent coupling constants
      (Reynolds numbers) Ren(k)=O(1). It is shown that in the infrared limit k
      >Lambdaf, the Reynolds numbers Re(k)->Retr, where Retr is the recently
      numerically and experimentally discovered universal Reynolds number of "smooth"
      transition from Gaussian to anomalous statistics of spatial velocity derivatives.
      The calculated relation Re(Lambdaf)=Retr "selects" the lowest-order nonlinearity
      as the only relevant one. This means that in the infrared limit k->Lambdaf, all
      high-order nonlinearities generated by the scale elimination sum up to zero.

PMID- 25375606
TI  - Concentration polarization, surface currents, and bulk advection in a
      microchannel.
AB  - We present a comprehensive analysis of salt transport and overlimiting currents
      in a microchannel during concentration polarization. We have carried out full
      numerical simulations of the coupled Poisson-Nernst-Planck-Stokes problem
      governing the transport and rationalized the behavior of the system. A remarkable
      outcome of the investigations is the discovery of strong couplings between bulk
      advection and the surface current; without a surface current, bulk advection is
      strongly suppressed. The numerical simulations are supplemented by analytical
      models valid in the long channel limit as well as in the limit of negligible
      surface charge. By including the effects of diffusion and advection in the
      diffuse part of the electric double layers, we extend a recently published
      analytical model of overlimiting current due to surface conduction. 

PMID- 25375607
TI  - Swimming fluctuations of micro-organisms due to heterogeneous microstructure.
AB  - Swimming microorganisms in biological complex fluids may be greatly influenced by
      heterogeneous media and microstructure with length scales comparable to the
      organisms. A fundamental effect of swimming in a heterogeneous rather than
      homogeneous medium is that variations in local environments lead to swimming
      velocity fluctuations. Here we examine long-range hydrodynamic contributions to
      these fluctuations using a Najafi-Golestanian swimmer near spherical and
      filamentous obstacles. We find that forces on microstructures determine changes
      in swimming speed. For macroscopically isotropic networks, we also show how the
      variance of the fluctuations in swimming speeds are related to density and
      orientational correlations in the medium. 

PMID- 25375608
TI  - Effect of correlation on viscosity and diffusion in molecular-dynamics
      simulations.
AB  - In the warm dense matter (WDM) regime, material properties like diffusion and
      viscosity can be obtained from lengthy quantum molecular dynamics simulations,
      where the quantum behavior of the electrons is represented using either Kohn-Sham
      or orbital-free density functional theory. To reduce the simulation duration, we
      fit the time dependence of the autocorrelation functions (ACFs) and then use the
      fit to find values of the diffusion and viscosity. This fitting procedure avoids
      noise in the long time behavior of the ACFs. We present a detailed analysis of
      the functional form used to fit the ACFs, which is always a more efficient means
      to obtain mass transport properties. We use the fits to estimate the statistical
      error of the transport properties. We apply this methodology to a dense
      correlated plasma of copper and a mixture of carbon and hydrogen. Both systems
      show structure in their ACFs and exhibit multiple time scales. The mixture
      contains different structural forms of the ACFs for each component in the
      mixture. 

PMID- 25375609
TI  - Field theory and weak Euler-Lagrange equation for classical particle-field
      systems.
AB  - It is commonly believed as a fundamental principle that energy-momentum
      conservation of a physical system is the result of space-time symmetry. However,
      for classical particle-field systems, e.g., charged particles interacting through
      self-consistent electromagnetic or electrostatic fields, such a connection has
      only been cautiously suggested. It has not been formally established. The
      difficulty is due to the fact that the dynamics of particles and the
      electromagnetic fields reside on different manifolds. We show how to overcome
      this difficulty and establish the connection by generalizing the Euler-Lagrange
      equation, the central component of a field theory, to a so-called weak form. The
      weak Euler-Lagrange equation induces a new type of flux, called the weak Euler
      Lagrange current, which enters conservation laws. Using field theory together
      with the weak Euler-Lagrange equation developed here, energy-momentum
      conservation laws that are difficult to find otherwise can be systematically
      derived from the underlying space-time symmetry. 

PMID- 25375610
TI  - Time-resolved measurement of global synchronization in the dust acoustic wave.
AB  - A spatially and temporally resolved measurement of the synchronization of the
      naturally occurring dust acoustic wave to an external drive and the relaxation
      from the driven wave mode back to the naturally occuring wave mode is presented.
      This measurement provides a time-resolved measurement of the synchronization of
      the self-excited dust acoustic wave with an external drive and the return to the
      self-excited mode. It is observed that the wave synchronizes to the external
      drive in a distinct time-dependent fashion, while there is an immediate loss of
      synchronization when the external modulation is discontinued. 

PMID- 25375611
TI  - Radially polarized, half-cycle, attosecond pulses from laser wakefields through
      coherent synchrotronlike radiation.
AB  - Attosecond bursts of coherent synchrotronlike radiation are found when driving
      ultrathin relativistic electron disks in a quasi-one-dimensional regime of
      wakefield acceleration, in which the laser waist is larger than the wake
      wavelength. The disks of overcritical density shrink radially due to focusing
      wakefields, thus providing the transverse currents for the emission of an
      intense, radially polarized, half-cycle pulse of about 100 attoseconds in
      duration. The electromagnetic pulse first focuses to a peak intensity
      (7*10(20)W/cm(2)) 10 times larger than the driving pulse and then emerges as a
      conical beam. Basic dynamics of the radiative process are derived analytically
      and in agreement with particle-in-cell simulations. By making use of gas targets
      instead of solids to form the ultrathin disks, this method allows for high
      repetition rates required for applications.

PMID- 25375612
TI  - Controllable parabolic-cylinder optical rogue wave.
AB  - We demonstrate controllable parabolic-cylinder optical rogue waves in certain
      inhomogeneous media. An analytical rogue wave solution of the generalized
      nonlinear Schrodinger equation with spatially modulated coefficients and an
      external potential in the form of modulated quadratic potential is obtained by
      the similarity transformation. Numerical simulations are performed for comparison
      with the analytical solutions and to confirm the stability of the rogue wave
      solution obtained. These optical rogue waves are built by the products of
      parabolic-cylinder functions and the basic rogue wave solution of the standard
      nonlinear Schrodinger equation. Such rogue waves may appear in different forms,
      as the hump and paw profiles. 

PMID- 25375613
TI  - Emulation of lossless exciton-polariton condensates by dual-core optical
      waveguides: stability, collective modes, and dark solitons.
AB  - We propose a possibility to simulate the exciton-polariton (EP) system in the
      lossless limit, which is not currently available in semiconductor microcavities,
      by means of a simple optical dual-core waveguide, with one core carrying the
      nonlinearity and operating close to the zero-group-velocity-dispersion point, and
      the other core being linear and dispersive. Both two-dimensional (2D) and one
      dimensional (1D) EP systems may be emulated by means of this optical setting. In
      the framework of this system, we find that, while the uniform state corresponding
      to the lower branch of the nonlinear dispersion relation is stable against small
      perturbations, the upper branch is always subject to the modulational
      instability. The stability and instability are verified by direct simulations
      too. We analyze collective excitations on top of the stable lower-branch state,
      which include a Bogoliubov-like gapless mode and a gapped one. Analytical results
      are obtained for the corresponding sound velocity and energy gap. The effect of a
      uniform phase gradient (superflow) on the stability is considered too, with a
      conclusion that the lower-branch state becomes unstable above a critical wave
      number of the flux. Finally, we demonstrate that the stable 1D state may carry
      robust dark solitons. 

PMID- 25375614
TI  - Mobility of discrete multibreathers in the exciton dynamics of the Davydov model
      with saturable nonlinearities.
AB  - We show that the state of amide-I excitations in proteins is modeled by the
      discrete nonlinear Schrodinger equation with saturable nonlinearities. This is
      done by extending the Davydov model to take into account the competition between
      local compression and local dilatation of the lattice, thus leading to the
      interplay between self-focusing and defocusing saturable nonlinearities. Site
      centered (sc) mode and/or bond-centered mode like discrete multihump soliton
      (DMHS) solutions are found numerically and their stability is analyzed. As a
      result, we obtained the existence and stability diagrams for all observed types
      of sc DMHS solutions. We also note that the stability of sc DMHS solutions
      depends not only on the value of the interpeak separation but also on the number
      of peaks, while their counterpart having at least one intersite soliton is
      instable. A study of mobility is achieved and it appears that, depending on the
      higher-order saturable nonlinearity, DMHS-like mechanism for vibrational energy
      transport along the protein chain is possible. 

PMID- 25375615
TI  - Theory of self-oscillation and mode locking in a longitudinal photoacoustic
      resonator.
AB  - The wave equation for pressure that governs generation of the photoacoustic
      effect possesses a forcing term proportional to the time derivative of the energy
      delivered to the gas per unit volume and time. A positive pressure fluctuation,
      with its accompanying density increase, thus increases the optical absorption and
      provides a positive feedback mechanism for sound generation. A theory for self
      oscillation in a one-dimensional resonator is given. Expressions for the
      photoacoustic pressure are derived for the cases of highly and weakly absorbing
      gases that indicate mode-locked sound generation. Experiments with CO2 lasers are
      reported where evidence of the self-generation effect was sought.

PMID- 25375616
TI  - Depolarization coefficients of light in multiply scattering media.
AB  - The depolarization coefficients are calculated for multiply scattered linearly
      and circularly polarized light. For a number of media (aqueous suspension of
      polystyrene particles, water droplets in air), the calculations are carried out
      both numerically, with solving the vector radiative transfer equation and
      analytically, within the polarization mode approximation. In the latter case the
      depolarization coefficients are expressed explicitly in terms of the scattering
      and absorption coefficients, and the scattering matrix elements of the medium.
      The range of applicability of the polarization mode approximation is established.
      For most practically important cases, this method is shown to provide a
      satisfactory degree of accuracy. We also find the fundamental values of the
      depolarization coefficients for a Rayleigh medium. 

PMID- 25375617
TI  - Improving self-calibration.
AB  - Response calibration is the process of inferring how much the measured data
      depend on the signal one is interested in. It is essential for any quantitative
      signal estimation on the basis of the data. Here, we investigate self-calibration
      methods for linear signal measurements and linear dependence of the response on
      the calibration parameters. The common practice is to augment an external
      calibration solution using a known reference signal with an internal calibration
      on the unknown measurement signal itself. Contemporary self-calibration schemes
      try to find a self-consistent solution for signal and calibration by exploiting
      redundancies in the measurements. This can be understood in terms of maximizing
      the joint probability of signal and calibration. However, the full uncertainty
      structure of this joint probability around its maximum is thereby not taken into
      account by these schemes. Therefore, better schemes, in sense of minimal square
      error, can be designed by accounting for asymmetries in the uncertainty of signal
      and calibration. We argue that at least a systematic correction of the common
      self-calibration scheme should be applied in many measurement situations in order
      to properly treat uncertainties of the signal on which one calibrates. Otherwise,
      the calibration solutions suffer from a systematic bias, which consequently
      distorts the signal reconstruction. Furthermore, we argue that nonparametric,
      signal-to-noise filtered calibration should provide more accurate reconstructions
      than the common bin averages and provide a new, improved self-calibration scheme.
      We illustrate our findings with a simplistic numerical example. 

PMID- 25375618
TI  - Boundary-controlled barostats for slab geometries in molecular dynamics
      simulations.
AB  - Molecular dynamics simulation barostat schemes are derived for achieving a given
      normal pressure for a thin liquid or solid layer confined between two parallel
      walls. This work builds on the boundary-controlled barostat scheme of Lupkowski
      and van Swol [J. Chem. Phys. 93, 737 (1990)]. Two classes of barostat are
      explored, one in which the external load is applied to a virtual regular lattice
      to which the wall atoms are bound using a tethering potential. The other type of
      barostat applies the external force directly to the wall atoms, which are not
      tethered. The extent to which the wall separation distribution is Gaussian is
      shown to be an effective measure of the quality of the barostat. The first class
      of barostat can suffer from anomalous dynamical signatures, even resonances,
      which are sensitive to the effective mass of the virtual lattice, whose value
      lacks any rigorous definition. The second type of barostat performs much better
      under equilibrium and wall-sliding nonequilibrium conditions and in not being so
      prone to resonance instabilities in the wall separation and does not require so
      many largely arbitrary parameters. The results of exploratory simulations which
      characterize the dynamical response of the model systems for both dry and wet or
      lubricated systems using the different barostats are presented. The barostats
      which have an inherent damping mechanism, such as the ones analogous to a damped
      harmonic oscillator, reduce the occurrence of large fluctuations and resonances
      in the separation between the two walls, and they also achieve a new target
      pressure more quickly. Near a nonequilibrium phase boundary the attributes of the
      barostat can have a marked influence on the observed behavior. 

PMID- 25375619
TI  - Fast algorithm for relaxation processes in big-data systems.
AB  - Relaxation processes driven by a Laplacian matrix can be found in many real-world
      big-data systems, for example, in search engines on the World Wide Web and the
      dynamic load-balancing protocols in mesh networks. To numerically implement such
      processes, a fast-running algorithm for the calculation of the pseudoinverse of
      the Laplacian matrix is essential. Here we propose an algorithm which computes
      quickly and efficiently the pseudoinverse of Markov chain generator matrices
      satisfying the detailed-balance condition, a general class of matrices including
      the Laplacian. The algorithm utilizes the renormalization of the Gaussian
      integral. In addition to its applicability to a wide range of problems, the
      algorithm outperforms other algorithms in its ability to compute within a
      manageable computing time arbitrary elements of the pseudoinverse of a matrix of
      size millions by millions. Therefore our algorithm can be used very widely in
      analyzing the relaxation processes occurring on large-scale networked systems. 

PMID- 25375620
TI  - Nonergodicity of the Nose-Hoover chain thermostat in computationally achievable
      time.
AB  - The widely used Nose-Hoover chain (NHC) thermostat in molecular dynamics
      simulations is generally believed to impart the canonical distribution as well as
      quasi- (i.e., space-filling) ergodicity on the thermostatted physical system
      (PS). Working with the standard single harmonic oscillator, we prove analytically
      that the two-chain Nose-Hoover thermostat with unequal thermostat masses
      approaches the standard Nose-Hoover dynamics, and hence the PS loses its
      canonical and quasiergodic nature. We also show through numerical simulations
      over substantially long times that for certain Poincare sections, for both the
      equal and unequal thermostat mass cases, the bivariate distribution function of
      position and momentum (x,p) and of reservoir degrees of freedom (xi,eta) lose
      their Gaussian nature. Further, the four-dimensional x-p-xi-eta extended phase
      space exhibits two holes of nonzero measure. The NHC thermostat therefore does
      not generate the canonical distribution or preserve quasiergodicity for the PS. 

PMID- 25375621
TI  - Accuracy of lattice Monte Carlo simulation of biased diffusion models.
AB  - The accuracy of lattice Monte Carlo (LMC) simulation of biased diffusion models
      is of great importance as far as the simulation credibility is concerned. It is
      known that the fixed time step LMC algorithm can reproduce the mean and the
      variance of the particle displacement exactly for all discrete time steps.
      Thereby, we propose to use the skewness and other quantities to measure the
      accuracy. For the one-dimensional fixed time step LMC simulation, we obtain an
      explicit expression for the skewness and find that the algorithm always produces
      a negative skewness that converges to zero in the long-time limit when the
      velocity is positive. It is proved that the skewness is inversely proportional to
      the square root of the number of simulation steps and the first step error only
      depends on the Peclet number. We further discuss several other measures of the
      accuracy of the approximation based on appropriately defined mean-square errors,
      leading to interesting, unexpected results. The accuracy measures can exhibit
      complicated nonmonotonic behavior and the optimal step size may depend on the
      measure of accuracy used. 

PMID- 25375622
TI  - Multispeed entropic lattice Boltzmann model for thermal flows.
AB  - An energy-conserving lattice Boltzmann (LB) model based on the entropic theory of
      admissible higher-order lattice is presented in detail. The entropy supporting
      'zero-one-three" lattice is used to construct a model capable of reproducing the
      full Fourier-Navier-Stokes equations at low Mach numbers. The proposed direct
      approach of constructing thermal models overcomes the shortcomings of existing
      models and retains one of the most important advantages of the LB methods, the
      exact space discretization of the advection step, thus paving the way for direct
      numerical simulation of thermal flows. New thermal wall boundary condition
      capable of handling curved geometries immersed in a multispeed lattice is
      proposed by extending the Tamm-Mott-Smith boundary condition. Entropic
      realization of the current model ensures stability of the model also for subgrid
      simulations. Numerical validation and thermodynamic consistency is demonstrated
      with classical setups such as thermal Couette flow, Rayleigh-Benard natural
      convection, acoustic waves, speed of sound measurements, and shock tube
      simulations. 

PMID- 25375623
TI  - Exhibiting cross-diffusion-induced patterns for reaction-diffusion systems on
      evolving domains and surfaces.
AB  - The aim of this manuscript is to present for the first time the application of
      the finite element method for solving reaction-diffusion systems with cross
      diffusion on continuously evolving domains and surfaces. Furthermore we present
      pattern formation generated by the reaction-diffusion system with cross-diffusion
      on evolving domains and surfaces. A two-component reaction-diffusion system with
      linear cross-diffusion in both u and v is presented. The finite element method is
      based on the approximation of the domain or surface by a triangulated domain or
      surface consisting of a union of triangles. For surfaces, the vertices of the
      triangulation lie on the continuous surface. A finite element space of functions
      is then defined by taking the continuous functions which are linear affine on
      each simplex of the triangulated domain or surface. To demonstrate the role of
      cross-diffusion to the theory of pattern formation, we compute patterns with
      model kinetic parameter values that belong only to the cross-diffusion parameter
      space; these do not belong to the standard parameter space for classical reaction
      diffusion systems. Numerical results exhibited show the robustness, flexibility,
      versatility, and generality of our methodology; the methodology can deal with
      complicated evolution laws of the domain and surface, and these include uniform
      isotropic and anisotropic growth profiles as well as those profiles driven by
      chemical concentrations residing in the domain or on the surface. 

PMID- 25375624
TI  - Comment on "Dependence of asymptotic decay exponents on initial condition and the
      resulting scaling violation".
AB  - We present the mapping relation between a one-dimensional conserved lattice gas
      model and a two species reaction A+B->0. From the kinetics of A+B->0, we show
      that the anomalous critical decay of an order parameter in the conserved lattice
      gas model results from finite-size effects induced by the domain structure for
      random initial conditions where the scaling relation z=nu?/nu? is violated. A
      simple initial condition satisfying the scaling relation is also discussed.

PMID- 25375625
TI  - XRCC1 gene polymorphisms and glioma risk in Chinese population: a meta-analysis.
AB  - BACKGROUND: Three extensively investigated polymorphisms (Arg399Gln, Arg194Trp,
      and Arg280His) in the X-ray repair cross-complementing group 1 (XRCC1) gene have
      been implicated in risk for glioma. However, the results from different studies
      remain inconsistent. To clarify these conflicts, we performed a quantitative
      synthesis of the evidence to elucidate these associations in the Chinese
      population. METHODS: Data were extracted from PubMed and EMBASE, with the last
      search up to August 21, 2014. Meta-analysis was performed by critically reviewing
      8 studies for Arg399Gln (3062 cases and 3362 controls), 8 studies for Arg194Trp
      (3419 cases and 3680 controls), and 5 studies for Arg280His (2234 cases and 2380
      controls). All of the statistical analyses were performed using the software
      program, STATA (version 11.0). RESULTS: Our analysis suggested that both
      Arg399Gln and Arg194Trp polymorphisms were significantly associated with
      increased risk of glioma (for Arg399Gln polymorphism: Gln/Gln vs. Arg/Arg, OR =
      1.82, 95% CI = 1.46-2.27, P = 0.000; Arg/Gln vs. Arg/Arg, OR = 1.25, 95% CI =
      1.10-1.42, P = 0.001 and for Arg194Trp polymorphism: recessive model, OR = 1.78,
      95% CI = 1.44-2.19, P = 0.000), whereas the Arg280His polymorphism had no
      influence on the susceptibility to glioma in a Chinese population. CONCLUSIONS:
      This meta-analysis suggests that there may be no association between the
      Arg280His polymorphism and glioma risk, whereas the Arg399Gln/Arg194Trp
      polymorphisms may contribute to genetic susceptibility to glioma in the Chinese
      population. Nevertheless, large-scale, well-designed and population-based studies
      are needed to further evaluate gene-gene and gene-environment interactions, as
      well as to measure the combined effects of these XRCC1 variants on glioma risk.

PMID- 25375626
TI  - Osteoradionecrosis of the subaxial cervical spine following treatment for head
      and neck carcinomas.
AB  - OBJECTIVE: To study MRI and positron emission tomography (PET)/CT imaging of
      osteoradionecrosis (ORN) of the subaxial cervical spine, a serious long-term
      complication of radiation therapy (RT) for head and neck cancers that can lead to
      pain, vertebral instability, myelopathy and cord compression. METHODS: This is a
      single-institution retrospective review of patients diagnosed and treated for ORN
      of the subaxial cervical spine following surgery and radiation for head and neck
      cancer. RESULTS: We report PET/CT imaging and MRI for four patients, each with
      extensive treatment for recurrent head and neck cancer. Osteomyelitis (OM) and
      discitis are the end-stage manifestations of ORN of the subaxial spine.
      CONCLUSION: ORN of the subaxial spine has variable imaging appearance and needs
      to be differentiated from recurrent or metastatic disease. Surgical violation of
      the posterior pharyngeal wall on top of the compromised vasculature in patients
      treated heavily with RT may pre-dispose the subaxial cervical vertebrae to ORN,
      with possible resultant OM and discitis. MRI and PET/CT imaging are complimentary
      in this setting. PET/CT images may be misinterpreted in view of the history of
      head and neck cancer. MRI should be utilized for definitive diagnosis of OM and
      discitis in view of its imaging specificity. ADVANCES IN KNOWLEDGE: We identify
      the end-stage manifestation of ORN in the sub-axial spine on PET/CT and MRI to
      facilitate its correct diagnosis.

PMID- 25375627
TI  - Recent epidemiological trends of dengue in the French territories of the Americas
      (2000-2012): a systematic literature review.
AB  - Dengue is a public health concern across the globe, and an escalating problem in
      the Americas. As part of a wider programme (covering Latin America and South East
      Asia) to characterize the epidemiology of dengue in dengue endemic areas, we
      undertook a systematic literature review to assess epidemiological trends
      (incidence, timing and duration of outbreaks/epidemics, age and sex distribution,
      serotype distribution, seroprevalence and disease severity) for dengue across the
      French Territories of the Americas (FTA), in French Guiana, Guadeloupe,
      Martinique, Saint Martin and Saint Barthelemy between 2000 and 2012
      (CRD42012002341:
      http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002341). Of 413
      relevant data sources identified, 45 were eligible for inclusion. A large
      proportion of the available data were from national surveillance reports, and 12
      publications were from peer-reviewed journals. During the review period, 3-5
      epidemics were identified in each of the island territories and French Guiana,
      and epidemics were often associated with a shift in the predominant circulating
      dengue virus serotype. Substantial gaps in epidemiological knowledge were
      identified. In particular, information regarding dengue virus genotype
      distribution, seroprevalence and age distribution of dengue were lacking.
      Additionally, much of the available data were from epidemic years; data from
      inter-epidemic periods were sparse. Nevertheless, the available epidemiological
      data showed that dengue is endemic across the FTA and suggest an evolution
      towards hyperendemicity, highlighting the need to continue the efforts with the
      existing surveillance programmes to assist in planning an effective vaccination
      programme once a dengue vaccine is deployed. PROTOCOL REGISTRATION: PROSPERO
      CRD42012002341.

PMID- 25375628
TI  - Structural controllability of complex networks based on preferential matching.
AB  - Minimum driver node sets (MDSs) play an important role in studying the structural
      controllability of complex networks. Recent research has shown that MDSs tend to
      avoid high-degree nodes. However, this observation is based on the analysis of a
      small number of MDSs, because enumerating all of the MDSs of a network is a #P
      problem. Therefore, past research has not been sufficient to arrive at a
      convincing conclusion. In this paper, first, we propose a preferential matching
      algorithm to find MDSs that have a specific degree property. Then, we show that
      the MDSs obtained by preferential matching can be composed of high- and medium
      degree nodes. Moreover, the experimental results also show that the average
      degree of the MDSs of some networks tends to be greater than that of the overall
      network, even when the MDSs are obtained using previous research method. Further
      analysis shows that whether the driver nodes tend to be high-degree nodes or not
      is closely related to the edge direction of the network. 

PMID- 25375630
TI  - Glycyrrhizic acid can attenuate metabolic deviations caused by a high-sucrose
      diet without causing water retention in male Sprague-Dawley rats.
AB  - Glycyrrhizic acid (GA) ameliorates many components of the metabolic syndrome, but
      its potential therapeutic use is marred by edema caused by inhibition of renal
      11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2). We assessed whether 100
      mg/kg per day GA administered orally could promote metabolic benefits without
      causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were
      fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a
      high-sucrose diet supplemented with GA. Rats were then culled and renal 11beta
      HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin
      levels were determined. Histological analyses were performed to assess changes in
      adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal
      tissue morphology. This dosing paradigm of GA attenuated the increases in serum
      leptin levels and visceral, but not subcutaneous adipocyte size caused by the
      high-sucrose diet. Although GA decreased renal 11beta-HSD2 activity, it did not
      affect serum electrolyte or angiotensin II levels, indicating no onset of edema.
      Furthermore, there were no apparent morphological changes in the liver or kidney,
      indicating no toxicity. In conclusion, it is possible to reap metabolic benefits
      of GA without edema using the current dosage and treatment time. 

PMID- 25375629
TI  - IFI16 restricts HSV-1 replication by accumulating on the hsv-1 genome, repressing
      HSV-1 gene expression, and directly or indirectly modulating histone
      modifications.
AB  - Interferon-gamma inducible factor 16 (IFI16) is a multifunctional nuclear protein
      involved in transcriptional regulation, induction of interferon-beta (IFN-beta),
      and activation of the inflammasome response. It interacts with the sugar
      phosphate backbone of dsDNA and modulates viral and cellular transcription
      through largely undetermined mechanisms. IFI16 is a restriction factor for human
      cytomegalovirus (HCMV) and herpes simplex virus (HSV-1), though the mechanisms of
      HSV-1 restriction are not yet understood. Here, we show that IFI16 has a profound
      effect on HSV-1 replication in human foreskin fibroblasts, osteosarcoma cells,
      and breast epithelial cancer cells. IFI16 knockdown increased HSV-1 yield 6-fold
      and IFI16 overexpression reduced viral yield by over 5-fold. Importantly, HSV-1
      gene expression, including the immediate early proteins, ICP0 and ICP4, the early
      proteins, ICP8 and TK, and the late proteins gB and Us11, was reduced in the
      presence of IFI16. Depletion of the inflammasome adaptor protein, ASC, or the IFN
      inducing transcription factor, IRF-3, did not affect viral yield. ChIP studies
      demonstrated the presence of IFI16 bound to HSV-1 promoters in osteosarcoma
      (U2OS) cells and fibroblasts. Using CRISPR gene editing technology, we generated
      U2OS cells with permanent deletion of IFI16 protein expression. ChIP analysis of
      these cells and wild-type (wt) U2OS demonstrated increased association of RNA
      polymerase II, TATA binding protein (TBP) and Oct1 transcription factors with
      viral promoters in the absence of IFI16 at different times post infection.
      Although IFI16 did not alter the total histone occupancy at viral or cellular
      promoters, its absence promoted markers of active chromatin and decreased those
      of repressive chromatin with viral and cellular gene promoters. Collectively,
      these studies for the first time demonstrate that IFI16 prevents association of
      important transcriptional activators with wt HSV-1 promoters and suggest
      potential mechanisms of IFI16 restriction of wt HSV-1 replication and a direct or
      indirect role for IFI16 in histone modification. 

PMID- 25375631
TI  - Oxidative damage and inflammation in obese diabetic Emirati subjects.
AB  - Visceral obesity is more common in the Arab population and more closely related
      to morbidity, including diabetes and related cardiovascular diseases (CVD).
      Possible mechanisms that link visceral fat/obesity to diabetes and CVD
      complications include inflammation and increased oxidative stress; however, few
      data are available from the Arab population. Our aim was to determine whether
      increased adiposity in obese diabetic United Arab Emirates citizens is associated
      with sub-clinical inflammation and/or increased oxidative stress. A hundred
      diabetic patients who were part of a randomized controlled trial of nutritional
      supplements had their baseline characteristics assessed from anthropometric and
      clinical data following informed written consent. We used WHO figures to classify
      general and central obesity. Fasting blood samples were collected for the
      measurement of antioxidants and markers of oxidative damage and inflammation. We
      found that increased adiposity measured by both body mass index and waist
      circumference was associated with increased C-reactive protein (CRP) and
      decreased vitamin C after adjusting for age, duration and treatment of diabetes
      (p < 0.05). Although there is a clear trend of increased inflammatory markers,
      notably CRP, and decreased antioxidants with increased BMI and waist
      circumference in both men and women, the results are statistically significant
      for women only. CRP were also inversely associated with HDL. Overall, we found
      that BMI underestimates the rates of obesity compared to waist circumference and
      that increased adiposity is associated with increased inflammation and decreased
      HDL and antioxidant status. 

PMID- 25375632
TI  - Selective augmentation of stem cell populations in structural fat grafts for
      maxillofacial surgery.
AB  - Structural fat grafting utilizes the centrifugation of liposuction aspirates to
      create a graded density of adipose tissue. This study was performed to
      qualitatively investigate the effects of centrifugation on stem cells present in
      adipose tissue. Liposuction aspirates were obtained from healthy donors and
      either not centrifuged or centrifuged at 1,800 rpm for 3 minutes. The obtained
      fat volumes were divided into three layers and then analyzed. The results
      demonstrate that centrifugation induces a different distribution of stem cells in
      the three layers. The high-density layer displays the highest expression of
      mesenchymal stem cell and endothelial markers. The low-density layer exhibits an
      enrichment of multipotent stem cells. We conclude that appropriate centrifugation
      concentrates stem cells. This finding may influence the clinical practice of
      liposuction aspirate centrifugation and enhance graft uptake. 

PMID- 25375633
TI  - Facile and universal superhydrophobic modification to fabricate waterborne,
      multifunctional nacre-mimetic films with excellent stability.
AB  - Although numerous kinds of waterborne, nacre-mimetic films with excellent
      properties have been fabricated via different assembly methods, it remains
      difficult to put those kinds of lightweight materials into practical applications
      because they are sensitive to water in the environment. Herein, a simple
      superhydrophobic modification method was used to enhance the repellency of film
      to water and/or corrosive liquids in the environment. Furthermore, it lowered the
      gas transmission rate of the films dramatically and improved the heat and flame
      shield capabilities. This approach could also be applied to other kinds of nacre
      mimetic films, proving to be a versatile, low-cost, fast, and facile method to
      produce large-area and thick, waterborne, multifunctional films with excellent
      repellency to water and some corrosive liquids in the environment, which will
      pave the road for the practical applications of nacre-mimetic films. 

PMID- 25375634
TI  - Low coherence interferometry approach for aiding fine needle aspiration biopsies.
AB  - We present portable preclinical low-coherence interference (LCI) instrumentation
      for aiding fine needle aspiration biopsies featuring the second-generation LCI
      based biopsy probe and an improved scoring algorithm for tissue differentiation.
      Our instrument and algorithm were tested on 38 mice with cultured tumor mass and
      we show the specificity, sensitivity, and positive predictive value of tumor
      detection of over 0.89, 0.88, and 0.96, respectively.

PMID- 25375635
TI  - Sc(OTf)3-mediated 1,3-dipolar cycloaddition-ring cleavage-rearrangement: a highly
      stereoselective access to Z-beta-enaminonitriles.
AB  - A novel and highly stereoselective synthesis of Z-beta-enaminonitriles from
      azides and alpha,beta-unsaturated nitriles is reported. The reaction proceeds via
      a 1,3-dipolar cycloaddition-ring cleavage-rearrangement cascade mediated by a
      catalytic amount of Sc(OTf)3. A plausible reaction mechanism for this process is
      depicted. 

PMID- 25375636
TI  - Epiphora after Uncomplicated Phacoemulsification: Study of Prevalence and
      Associated Factors.
AB  - PURPOSE: To describe the prevalence of epiphora and associated factors after
      uncomplicated phacoemulsification. METHODS: Prospective and descriptive design. A
      group of 125 patients was asked about tearing one to two weeks after cataract
      surgery. A comprehensive examination was performed on the patients who answered
      affirmatively. All patients were re-interviewed by phone after three months and
      those who complained of epiphora were explored again. RESULTS: Two weeks after
      surgery, prevalence of epiphora was 10.4%, but only 3.2% appeared after surgery.
      In patients with preoperative epiphora, the most frequently associated factors
      were ocular surface alterations (89%) and unctual and canalicular stenosis (56%).
      In patients with "new onset" epiphora (4 patients), these factors were:
      blepharitis (2/4), low tear break-up time (2/4), high tear meniscus (2/4),
      partial nasolacrimal duct obstruction (2/4), and unctual stenosis (1/4). Three
      months after surgery, the prevalence of epiphora was 13%, but only 7% appeared
      after surgery (6 patients). Of those 6 patients, 4 were re-examined: nasolacrimal
      duct obstruction (2/4), ocular surface problems (3/4), and unctual stenosis
      (1/4). CONCLUSIONS: Presence of epiphora two weeks after phacoemulsification was
      infrequent, despite being present in a high proportion of patients before
      surgery. There was not a noticeable increase in epiphora at three months. The
      most frequently related factors were mixed disorders of the ocular surface and
      lacrimal system, without an important incidence of unctual and canalicular
      stenosis. We consider that our perception about complaints from patients after
      phacoemulsification may be biased due to those who had previously suffered from
      epiphora.

PMID- 25375637
TI  - Biospecimen long-chain N-3 PUFA and risk of colorectal cancer: a meta-analysis of
      data from 60,627 individuals.
AB  - BACKGROUND: Several prospective cohort and case-control studies reported the
      inconsistent association between biospecimen composition of C20 and C22 long
      chain (LC) n-3 polyunsaturated fatty acid (PUFA) and colorectal cancer (CRC)
      risk. The aim of the present study was to investigate the association of
      biospecimen LC n-3 PUFA with CRC risk based on prospective cohort and case
      control studies. METHODS AND RESULTS: Cochrane Library, PubMed, and EMBASE
      database were searched up to February 2014 for eligible studies. Risk ratios
      (RRs) or odds ratios (ORs) from prospective and case-control studies were
      combined using a random-effects model in the highest vs. lowest categorical
      analysis. Nonlinear dose-response relationships were assessed using restricted
      cubic spline regression models. Difference in tissue composition of LC n-3 PUFA
      between cases and noncases was analyzed as standardized mean difference (SMD).
      Three prospective cohort studies and 8 case-control studies were included in the
      present study, comprising 60,627 participants (1,499 CRC cases and 59,128
      noncases). Higher biospecimen LC n-3 PUFA was significantly associated with a
      lower risk of CRC in case-control (pooled OR: 0.76; 95% CI: 0.59, 0.97; I2 =
      10.00%) and prospective cohort studies (pooled RR: 0.70; 95% CI: 0.55, 0.88; I2 =
      0.00%), respectively. A significant dose-response association was found of
      biospecimen C20:5n-3 (P for nonlinearity  = 0.02) and C22:6n-3 (P for trend  =
      0.01) with CRC risk, respectively. Subjects without CRC have significantly higher
      biospecimen compositions of C20:5n-3 (SMD: 0.27; 95%: 0.13, 0.41), C22:6n-3 (SMD:
      0.23; 95%: 0.11, 0.34) and total LC n-3 PUFA (SMD: 0.22; 95% CI: 0.07, 0.37)
      compared with those with CRC. CONCLUSIONS: The present evidence suggests human
      tissue compositions of LC n-3 PUFA may be an independent predictive factor for
      CRC risk, especially C20:5n-3 and C22:6n-3. This needs to be confirmed with more
      large-scale prospective cohort studies.

PMID- 25375640
TI  - Aggregation and sedimentation of Thalassiosira weissflogii (diatom) in a warmer
      and more acidified future ocean.
AB  - Increasing Transparent Exopolymer Particle (TEP) formation during diatom blooms
      as a result of elevated temperature and pCO2 have been suggested to result in
      enhanced aggregation and carbon flux, therewith potentially increasing the
      sequestration of carbon by the ocean. We present experimental results on TEP and
      aggregate formation by Thalassiosira weissflogii (diatom) in the presence or
      absence of bacteria under two temperature and three pCO2 scenarios. During the
      aggregation phase of the experiment TEP formation was elevated at the higher
      temperature (20 degrees C vs. 15 degrees C), as predicted. However, in contrast
      to expectations based on the established relationship between TEP and
      aggregation, aggregation rates and sinking velocity of aggregates were depressed
      in warmer treatments, especially under ocean acidification conditions. If our
      experimental findings can be extrapolated to natural conditions, they would imply
      a reduction in carbon flux and potentially reduced carbon sequestration after
      diatom blooms in the future ocean.

PMID- 25375641
TI  - Trm4 and Nsun2 RNA:m5C methyltransferases form metabolite-dependent, covalent
      adducts with previously methylated RNA.
AB  - Trm4p from Saccharomyces cerevisiae and its mammalian orthologue Nsun2 fabricate
      5-methylcytosine (m(5)C) in RNA molecules utilizing a dual-cysteine catalytic
      mechanism. These enzymes are now shown to form covalent complexes with previously
      methylated RNA. Enzyme linkage to methylated RNA requires S-adenosylhomocysteine
      (AdoHcy), and the removal of this metabolite results in the disassembly of
      preexisting complexes. The fraction of Trm4p linked to modified RNA is influenced
      by the AdoHcy concentration and by the pH of the solution, with maximal formation
      of Trm4p-RNA complexes observed in the pH range of 5.5-6.5. Four active-site
      residues critical for Trm4p-mediated tRNA methylation are also required for the
      formation of the denaturant-resistant complexes with m(5)C-containing RNA. On the
      basis of these findings, it is proposed that formation of a covalent complex
      between dual-cysteine RNA:m(5)C methyltransferases and methylated RNA provides a
      unique means by which metabolic factors can influence RNA. By controlling the
      degree of formation of the enzyme-RNA covalent complex, AdoHcy and pH are likely
      to influence the extent of m(5)C formation and the rate of release of methylated
      RNA from RNA:m(5)C methyltransferases. Metabolite-induced covalent complexes
      could plausibly affect the processing and function of m(5)C-containing RNAs. 

PMID- 25375638
TI  - Predictive gene signature of response to the anti-TweakR mAb PDL192 in patient
      derived breast cancer xenografts.
AB  - PURPOSE: (1) To determine TweakR expression in human breast cancers (BC), (2)
      evaluate the antitumor effect of the anti-TweakR antibody PDL192, used alone or
      after chemotherapy-induced complete remission (CR), on patient-derived BC
      xenografts (PDX) and (3) define predictive markers of response. EXPERIMENTAL
      DESIGN: TweakR expression was analyzed by IHC on patients and PDXs BC samples. In
      vivo antitumor effect of PDL192 was evaluated on eight TweakR-positive BC PDXs
      alone or after complete remission induced by a combination of doxorubicin and
      cyclophosphamide. Using both responding and resistant PDX tumors after PDL192
      administration, RT-QPCR were performed on a wide list of selected candidate genes
      to identify predictive markers of response. RESULTS: TweakR protein was expressed
      in about half of human BC samples. In vivo PDL192 treatment had significantly
      anti-tumor activity in 4 of 8 TweakR-positive BC PDXs, but no correlation between
      the expression level of the Tweak receptor and response to therapy was observed.
      PDL192 also significantly delayed tumor relapse after CR. Finally, an 8 gene
      signature was defined from sensitive and resistant PDXs. CONCLUSIONS: PDL192 was
      highly efficient in some BC PDXs. We found 8 genes that were differentially
      expressed in responding and resistant tumors and could constitute a gene
      expression signature which would need to be extended to other xenograft models
      for confirmation. These data confirm the therapeutic potential of TweakR
      targeting in BC and the possibility of prospectively selecting patients who might
      benefit from therapy.

PMID- 25375642
TI  - Free preconceptual screening examination service in rural areas of Hubei
      Province, China in 2012.
AB  - OBJECTIVE: This work aims to collect and summarize the outcomes on free
      preconceptual screening examination in rural areas of Hubei Province in 2012.
      Moreover, this review promotes further understanding of the status of this
      activity to provide the Family Planning Commission valid scientific data upon
      which to construct effective policies. METHODS: Couples, who complied with the
      family planning policy and were the residents in agricultural areas or lived in a
      local rural area for more than six months, were encouraged to participate in the
      free preconceptual screening examination service provided by the Hubei Provincial
      Population and Family Planning Commission. This service included 19 screening
      tests. All the data, including forms, manuals, and test results, were collected
      from 1 January 2012 to 31 December 2012 in rural areas in Hubei Province.
      RESULTS: A total of 497,860 individuals participated in the free preconceptual
      screening examination service, with a coverage rate of 97.1%. 4.0% and 4.8% of
      the participants exhibited with abnormal blood levels of ALT and creatinine,
      respectively; 0.36% of the participants tested positive for syphilis; 0.44% and
      3.6% of the female participants tested positive for Neisseria gonorrhoeae and
      Chlamydia trachomatis, respectively; and 0.84% and 1.8% of the female
      participants tested positive for cytomegalovirus (IgM) and Toxoplasma gondii
      (IgM), respectively. After risk assessment, 59,935 participants might have high
      risk of adverse pregnancy outcomes. In 2012, the prevalence of birth defects
      among the parturient who participated in the preconceptual screening examination
      service was 0.04%, while the prevalence was 0.08% among those who did not
      participate in the service. CONCLUSION: Preconceptual screening examination
      service may help to address the risk factors that can lead to adverse pregnancy
      outcome. More studies on the relationship between preconceptual screening
      examination service and prevalence of birth defect or other adverse pregnancy
      outcomes should be conducted.

PMID- 25375643
TI  - Polyacrylic acid-coated iron oxide nanoparticles for targeting drug resistance in
      mycobacteria.
AB  - The emergence of drug resistance is a major problem faced in current tuberculosis
      (TB) therapy, representing a global health concern. Mycobacterium is naturally
      resistant to most drugs due to export of the latter outside bacterial cells by
      active efflux pumps, resulting in a low intracellular drug concentration. Thus,
      development of agents that can enhance the effectiveness of drugs used in TB
      treatment and bypass the efflux mechanism is crucial. In this study, we present a
      new nanoparticle-based strategy for enhancing the efficacy of existing drugs. To
      that end, we have developed poly(acrylic acid) (PAA)-coated iron oxide
      (magnetite) nanoparticles (PAA-MNPs) as efflux inhibitors and used it together
      with rifampicin (a first line anti-TB drug) on Mycobacterium smegmatis. PAA-MNPs
      of mean diameter 9 nm interact with bacterial cells via surface attachment and
      are then internalized by cells. Although PAA-MNP alone does not inhibit cell
      growth, treatment of cells with a combination of PAA-MNP and rifampicin exhibits
      a synergistic 4-fold-higher growth inhibition compared to rifampicin alone. This
      is because the combination of PAA-MNP and rifampicin results in up to a 3-fold
      increased accumulation of rifampicin inside the cells. This enhanced
      intracellular drug concentration has been explained by real-time transport
      studies on a common efflux pump substrate, ethidium bromide (EtBr). It is seen
      that PAA-MNP increases the accumulation of EtBr significantly and also minimizes
      the EtBr efflux in direct proportion to the PAA-MNP concentration. Our results
      thus illustrate that the addition of PAA-MNP with rifampicin may bypass the
      innate drug resistance mechanism of M. smegmatis. This generic strategy is also
      found to be successful for other anti-TB drugs, such as isoniazid and
      fluoroquinolones (e.g., norfloxacin), only when stabilized, coated nanoparticles
      (such as PAA-MNP) are used, not PAA or MNP alone. We hence establish coated
      nanoparticles as a new class of efflux inhibitors for potential therapeutic use. 

PMID- 25375645
TI  - Dissociation constants of weak acids from ab initio molecular dynamics using
      metadynamics: influence of the inductive effect and hydrogen bonding on pKa
      values.
AB  - The theoretical estimation of the dissociation constant, or pKa, of weak acids
      continues to be a challenging field. Here, we show that ab initio Car-Parrinello
      molecular dynamics simulations in conjunction with metadynamics calculations of
      the free-energy profile of the dissociation reaction provide reasonable estimates
      of the pKa value. Water molecules, sufficient to complete the three hydration
      shells surrounding the acid molecule, were included explicitly in the computation
      procedure. The free-energy profiles exhibit two distinct minima corresponding to
      the dissociated and neutral states of the acid, and the difference in their
      values provides the estimate for pKa. We show for a series of organic acids that
      CPMD simulations in conjunction with metadynamics can provide reasonable
      estimates of pKa values. The acids investigated were aliphatic carboxylic acids,
      chlorine-substituted carboxylic acids, cis- and trans-butenedioic acid, and the
      isomers of hydroxybenzoic acid. These systems were chosen to highlight that the
      procedure could correctly account for the influence of the inductive effect as
      well as hydrogen bonding on pKa values of weak organic acids. In both situations,
      the CPMD metadynamics procedure faithfully reproduces the experimentally observed
      trend and the magnitudes of the pKa values. 

PMID- 25375644
TI  - Can cognitive activities during breaks in repetitive manual work accelerate
      recovery from fatigue? A controlled experiment.
AB  - Neurophysiologic theory and some empirical evidence suggest that fatigue caused
      by physical work may be more effectively recovered during "diverting" periods of
      cognitive activity than during passive rest; a phenomenon of great interest in
      working life. We investigated the extent to which development and recovery of
      fatigue during repeated bouts of an occupationally relevant reaching task was
      influenced by the difficulty of a cognitive activity between these bouts.
      Eighteen male volunteers performed three experimental sessions, consisting of six
      7-min bouts of reaching alternating with 3 minutes of a memory test differing in
      difficulty between sessions. Throughout each session, recordings were made of
      upper trapezius muscle activity using electromyography (EMG), heart rate and
      heart rate variability (HRV) using electrocardiography, arterial blood pressure,
      and perceived fatigue (Borg CR10 scale and SOFI). A test battery before,
      immediately after and 1 hour after the work period included measurements of
      maximal shoulder elevation strength (MVC), pressure pain threshold (PPT) over the
      trapezius muscles, and a submaximal isometric contraction. As expected, perceived
      fatigue and EMG amplitude increased during the physical work bouts. Recovery did
      occur between the bouts, but fatigue accumulated throughout the work period.
      Neither EMG changes nor recovery of perceived fatigue during breaks were
      influenced by cognitive task difficulty, while heart rate and HRV recovered the
      most during breaks with the most difficult task. Recovery of perceived fatigue
      after the 1 hour work period was also most pronounced for the most difficult
      cognitive condition, while MVC and PPT showed ambiguous patterns, and EMG
      recovered similarly after all three cognitive protocols. Thus, we could confirm
      that cognitive tasks between bouts of fatiguing physical work can, indeed,
      accelerate recovery of some factors associated with fatigue, even if benefits may
      be moderate and some responses may be equivocal. Our results encourage further
      research into combinations of physical and mental tasks in an occupational
      context. 

PMID- 25375646
TI  - Efficient uptake of blood-borne BK and JC polyomavirus-like particles in
      endothelial cells of liver sinusoids and renal vasa recta.
AB  - Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that
      mediate high-capacity clearance of soluble waste macromolecules and colloid
      material, including blood-borne adenovirus. To explore if LSECs function as a
      sink for other viruses in blood, we studied the fate of virus-like particles
      (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like
      complete virions, VLPs specifically bind to receptors and enter cells, but unlike
      complete virions, they cannot replicate. 125I-labeled VLPs were used to assess
      blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled
      VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC
      VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver
      uptake was predominantly in LSECs. Blood half-life (~1 min), and tissue
      distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic
      acid binding affinity, were similar, indicating involvement of non-sialic acid
      receptors in cellular uptake. Liver uptake was not mediated by scavenger
      receptors. In spleen, the VLPs localized to the red pulp marginal zone
      reticuloendothelium, and in kidney to the endothelial lining of vasa recta
      segments, and the transitional epithelium of renal pelvis. Most VLP-positive
      vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the
      non-fenestrated part of vasa recta. The endothelial cells of these vessels also
      efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured
      albumin, suggesting high endocytic activity compared to other renal endothelia.
      We conclude that LSECs very effectively cleared a large fraction of blood-borne
      BK- and JC-VLPs, indicating a central role of these cells in early removal of
      polyomavirus from the circulation. In addition, we report the novel finding that
      a subpopulation of endothelial cells in kidney, the main organ of polyomavirus
      persistence, showed selective and rapid uptake of VLPs, suggesting a role in
      viremic organ tropism. 

PMID- 25375648
TI  - Characterizing air temperature changes in the Tarim Basin over 1960-2012.
AB  - There has been evidence of warming rate varying largely over space and between
      seasons. However, little has been done to evaluate the spatial and temporal
      variability of air temperature in the Tarim Basin, northwest China. In this
      study, we collected daily air temperature from 19 meteorological stations for the
      period of 1960-2012, and analyzed annual mean temperature (AMT), the annual
      minimum (T min) and maximum temperature (Tmax), and mean temperatures of all
      twelve months and four seasons and their anomalies. Trend analyses, standard
      deviation of the detrended anomaly (SDDA) and correlations were carried out to
      characterize the spatial and temporal variability of various mean air
      temperatures. Our data showed that increasing trend was much greater in the T min
      (0.55 degrees C/10a) than in the AMT (0.25 degrees C/10a) and Tmax (0.12 degrees
      C/10a), and the fluctuation followed the same order. There were large spatial
      variations in the increasing trends of both AMT (from -0.09 to 0.43  degrees
      C/10a) and T min (from 0.15 to 1.12 degrees C/10a). Correlation analyses
      indicated that AMT had a significantly linear relationship with T min and the
      mean temperatures of four seasons. There were also pronounced changes in the
      monthly air temperature from November to March at decadal time scale. The
      seasonality (i.e., summer and winter difference) of air temperature was stronger
      during the period of 1960-1979 than over the recent three decades. Our
      preliminary analyses indicated that local environmental conditions (such as
      elevation) might be partly responsible for the spatial variability, and large
      scale climate phenomena might have influences on the temporal variability of air
      temperature in the Tarim Basin. In particular, there was a significant
      correlation between index of El Nino-Southern Oscillation (ENSO) and air
      temperature of May (P = 0.004), and between the index of Pacific Decadal
      Oscillation (PDO) and air temperature of July (P = 0.026) over the interannual to
      decadal time scales.

PMID- 25375647
TI  - Effect of pneumococcal conjugate vaccination in Uruguay, a middle-income country.
AB  - BACKGROUND: In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7) was
      introduced into the routine childhood immunization program in Uruguay, with a 2+1
      schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The
      effect of these pneumococcal vaccines on the incidence of invasive pneumococcal
      infections (IPD) and on serotype distribution was analyzed retrospectively, based
      on passive national laboratory surveillance. METHODS: Data from 1,887 IPD
      isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3
      after PCV13 introduction) was examined to assess the incidence rate per 100,000
      age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes
      associated IPD among children < 2 years and 2 to 4 years old, and patients >= 5
      years old. Trends of frequency for each serotype were also analyzed. RESULTS:
      Comparison of pre-vaccination (2003-2007) and post-vaccination (2008-2012)
      periods showed a significant decrease in IPD incidence among children < 2 years
      old (IR 68.7 to IR 29.6, p<0.001) and children 2 to 4 years (p < 0.04). IPD
      caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes
      added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of
      both conjugate vaccines were observed among patients >= 5 years old one year
      after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13.
      Nevertheless, for reasons that still need to be explained, perhaps due to
      ascertainment bias, total IPD in this group increased after 2007. In 2012, the
      relative frequency of vaccine serotypes among vaccinated and unvaccinated
      population declined, except for serotype 3. Non vaccine serotypes with increasing
      frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and
      33. CONCLUSION: Consecutive immunization with PCV7 and PCV13 has significantly
      reduced IPD in children < 5 years of age in Uruguay.

PMID- 25375649
TI  - Global assessment of seasonal potential distribution of Mediterranean fruit fly,
      Ceratitis capitata (Diptera: Tephritidae).
AB  - The Mediterranean fruit fly (Medfly) is one of the world's most economically
      damaging pests. It displays highly seasonal population dynamics, and the
      environmental conditions suitable for its abundance are not constant throughout
      the year in most places. An extensive literature search was performed to obtain
      the most comprehensive data on the historical and contemporary spatio-temporal
      occurrence of the pest globally. The database constructed contained 2328 unique
      geo-located entries on Medfly detection sites from 43 countries and nearly 500
      unique localities, as well as information on hosts, life stages and capture
      method. Of these, 125 localities had information on the month when Medfly was
      recorded and these data were complemented by additional material found in
      comprehensive databases available online. Records from 1980 until present were
      used for medfly environmental niche modeling. Maximum Entropy Algorithm (MaxEnt)
      and a set of seasonally varying environmental covariates were used to predict the
      fundamental niche of the Medfly on a global scale. Three seasonal maps were also
      produced: January-April, May-August and September-December. Models performed
      significantly better than random achieving high accuracy scores, indicating a
      good discrimination of suitable versus unsuitable areas for the presence of the
      species. 

PMID- 25375651
TI  - Discovering new agents active against methicillin-resistant Staphylococcus aureus
      with ligand-based approaches.
AB  - To discover new agents active against methicillin-resistant Staphylococcus aureus
      (MRSA), in silico models derived from 5451 cell-based anti-MRSA assay data were
      developed using four machine learning methods, including naive Bayesian, support
      vector machine (SVM), recursive partitioning (RP), and k-nearest neighbors (kNN).
      A total of 876 models have been constructed based on physicochemical descriptors
      and fingerprints. The overall predictive accuracies of the best models exceeded
      80% for both training and test sets. The best model was employed for the virtual
      screening of anti-MRSA compounds, which were then validated by a cell-based assay
      using the broth microdilution method with three types of highly resistant MRSA
      strains (ST239, ST5, and 252). A total of 12 new anti-MRSA agents were confirmed,
      which had MIC values ranging from 4 to 64 mg/L. This work proves the capacity of
      combined multiple ligand-based approaches for the discovery of new agents active
      against MRSA with cell-based assays. We think this work may inspire other lead
      identification processes when cell-based assay data are available. 

PMID- 25375652
TI  - Desvenlafaxine 50 and 100 mg/d versus placebo for the treatment of major
      depressive disorder: a phase 4, randomized controlled trial.
AB  - OBJECTIVE: To assess short-term efficacy and safety of desvenlafaxine 50 and 100
      mg/d versus placebo for treating major depressive disorder (MDD). Assessment of
      sexual function was a secondary objective. METHOD: Outpatients (>= 18 years) who
      met criteria for MDD from the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision and had screening and baseline 17-item
      Hamilton Depression Rating Scale (HDRS17) total scores >= 20 were randomly
      assigned to placebo or desvenlafaxine 50 or 100 mg/d in an 8-week study conducted
      from October 2011 to August 2012. The primary efficacy end point was change from
      baseline in HDRS17 total score at week 8, analyzed using a mixed-effects model
      for repeated measures. Sexual function was assessed using the Arizona Sexual
      Experiences Scale (ASEX). RESULTS: The safety population included 909 patients
      (intent-to-treat population, n = 886). Significantly greater improvement in
      adjusted mean HDRS17 total score from baseline to week 8 was observed for
      desvenlafaxine 50 mg (-11.28; P = .006) and desvenlafaxine 100 mg (-11.67; P <
      .001) compared with placebo (-9.71), with adjustment for multiplicity. In the
      ASEX total score analysis (n = 422), the treatment by gender interaction was not
      significant; thus, genders were combined for subsequent analyses. Comparisons for
      desvenlafaxine versus placebo for change from baseline in ASEX total and all item
      scores found P > .05, with no adjustment for multiplicity. Rates of sexual
      dysfunction based on ASEX were comparable among treatment groups. CONCLUSIONS:
      These results support previous findings demonstrating antidepressant efficacy,
      safety, and tolerability of desvenlafaxine 50 and 100 mg/d versus placebo. Sexual
      function was comparable between desvenlafaxine and placebo. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01432457.

PMID- 25375653
TI  - Is it time for BRCA1/2 mutation screening in the general adult population?:
      impact of population characteristics.

PMID- 25375650
TI  - Genome-wide associations between genetic and epigenetic variation influence mRNA
      expression and insulin secretion in human pancreatic islets.
AB  - Genetic and epigenetic mechanisms may interact and together affect biological
      processes and disease development. However, most previous studies have
      investigated genetic and epigenetic mechanisms independently, and studies
      examining their interactions throughout the human genome are lacking. To identify
      genetic loci that interact with the epigenome, we performed the first genome-wide
      DNA methylation quantitative trait locus (mQTL) analysis in human pancreatic
      islets. We related 574,553 single nucleotide polymorphisms (SNPs) with genome
      wide DNA methylation data of 468,787 CpG sites targeting 99% of RefSeq genes in
      islets from 89 donors. We identified 67,438 SNP-CpG pairs in cis, corresponding
      to 36,783 SNPs (6.4% of tested SNPs) and 11,735 CpG sites (2.5% of tested CpGs),
      and 2,562 significant SNP-CpG pairs in trans, corresponding to 1,465 SNPs (0.3%
      of tested SNPs) and 383 CpG sites (0.08% of tested CpGs), showing significant
      associations after correction for multiple testing. These include reported
      diabetes loci, e.g. ADCY5, KCNJ11, HLA-DQA1, INS, PDX1 and GRB10. CpGs of
      significant cis-mQTLs were overrepresented in the gene body and outside of CpG
      islands. Follow-up analyses further identified mQTLs associated with gene
      expression and insulin secretion in human islets. Causal inference test (CIT)
      identified SNP-CpG pairs where DNA methylation in human islets is the potential
      mediator of the genetic association with gene expression or insulin secretion.
      Functional analyses further demonstrated that identified candidate genes (GPX7,
      GSTT1 and SNX19) directly affect key biological processes such as proliferation
      and apoptosis in pancreatic beta-cells. Finally, we found direct correlations
      between DNA methylation of 22,773 (4.9%) CpGs with mRNA expression of 4,876
      genes, where 90% of the correlations were negative when CpGs were located in the
      region surrounding transcription start site. Our study demonstrates for the first
      time how genome-wide genetic and epigenetic variation interacts to influence gene
      expression, islet function and potential diabetes risk in humans.

PMID- 25375654
TI  - Clinical aspects of Usher syndrome and the USH2A gene in a cohort of 433
      patients.
AB  - IMPORTANCE: A new statistical approach is needed to describe the clinical
      differences between type I and type II Usher syndrome and between the 2 most
      frequent mutations in the USH2A gene. OBJECTIVES: To describe the primary
      phenotypic characteristics and differences between type I and type II Usher
      syndrome and to establish a phenotype-genotype correlation for the 2 most
      frequent mutations in the USH2A gene. DESIGN, SETTING, AND PARTICIPANTS: Cross
      sectional study at a genetics department, in which clinical evaluations were
      performed for 433 patients (297 unrelated families) who were classified as having
      type I, II, III, atypical, or unclassified Usher syndrome according to their
      clinical history, pedigree data, results from ophthalmological studies, and
      audiological, neurophysiological, and vestibular test results. Molecular studies
      were performed for 304 patients (256 unrelated families). The Mann-Whitney U test
      or the chi2 test was used for calculating the differences between mean values for
      the analyzed parameters. MAIN OUTCOMES AND MEASURES: Age at diagnosis; age at
      onset of night blindness, visual field loss, visual acuity loss, and cataracts;
      and severity and age at diagnosis of hearing loss. RESULTS: The comparison
      between patients with type I Usher syndrome and those with type II Usher syndrome
      revealed P < .001 for most items analyzed. The most frequent mutations in the
      USH2A gene were the p.Glu767Serfs*21 and p.Cys759Phe mutations, with an allelic
      frequency of 23.2% (63 of 272 alleles) and 8.1% (22 of 272 alleles),
      respectively. The phenotypic analysis for patients carrying p.Cys759Phe showed P
      < .001 for most items analyzed when compared with patients carrying
      p.Glu767Serfs*21 and when compared with patients carrying other mutations in the
      USH2A gene. None of the p.Cys759Phe patients exhibited a severe hearing loss
      phenotype, and more than 60% had only mild hearing loss. Most patients carrying
      the p.Glu767Serfs*21 mutation (72.1%) were moderately deaf. CONCLUSIONS AND
      RELEVANCE: Our study presents the clinical differences between type I and type II
      Usher syndrome and between the 2 most frequent mutations in the USH2A gene.
      Detailed genotype-phenotype correlations, as presented in our study, allow for a
      better correlation of clinical signs with a known genotype and can improve the
      clinical management, genetic counseling, and risk assessment of patients with
      Usher syndrome because an estimated prognosis of their disease can be made.

PMID- 25375655
TI  - The ethics of our inquiry: an interview with Hank Greely.

PMID- 25375656
TI  - Spatial structure and distribution of small pelagic fish in the northwestern
      Mediterranean Sea.
AB  - Understanding the ecological and anthropogenic drivers of population dynamics
      requires detailed studies on habitat selection and spatial distribution. Although
      small pelagic fish aggregate in large shoals and usually exhibit important
      spatial structure, their dynamics in time and space remain unpredictable and
      challenging. In the Gulf of Lions (north-western Mediterranean), sardine and
      anchovy biomasses have declined over the past 5 years causing an important
      fishery crisis while sprat abundance rose. Applying geostatistical tools on
      scientific acoustic surveys conducted in the Gulf of Lions, we investigated
      anchovy, sardine and sprat spatial distributions and structures over 10 years.
      Our results show that sardines and sprats were more coastal than anchovies. The
      spatial structure of the three species was fairly stable over time according to
      variogram outputs, while year-to-year variations in kriged maps highlighted
      substantial changes in their location. Support for the McCall's basin hypothesis
      (covariation of both population density and presence area with biomass) was found
      only in sprats, the most variable of the three species. An innovative method to
      investigate species collocation at different scales revealed that globally the
      three species strongly overlap. Although species often co-occurred in terms of
      presence/absence, their biomass density differed at local scale, suggesting
      potential interspecific avoidance or different sensitivity to local environmental
      characteristics. Persistent favourable areas were finally detected, but their
      environmental characteristics remain to be determined. 

PMID- 25375657
TI  - FOSL2 positively regulates TGF-beta1 signalling in non-small cell lung cancer.
AB  - Fos-related antigen 2 (FRA-2/FOSL2) belongs to the AP-1 transcription factor
      family. Although FOSL2 has been shown to be involved in diverse physiological and
      pathological processes, very little is known about the signalling pathways that
      regulate FOSL2 expression and the mechanisms of FOSL2 function. Here, we show
      that FOSL2 expression is regulated by TGF-beta1 and that FOSL2 is required for
      TGF-beta1-induced migration. We demonstrate that FOSL2 interacts with Smad3 in
      vitro and in vivo and thus up-regulates TGF-beta1-induced signalling responses.
      Mechanistically, FOSL2 promotes P300 binding to Smad3 and the acetylation of
      Smad3 by P300. Furthermore, we show that the expression of FOSL2 correlates with
      activated Smad3 expression in clinical non-small cell lung cancer (NSCLC)
      samples. In summary, the present study indicates that FOSL2 facilitates TGF-beta1
      induced migration by interaction with Smad3 in NSCLC and suggests FOSL2 as a
      potential therapeutic target for NSCLC. 

PMID- 25375658
TI  - Cell proliferation and neurogenesis in adult mouse brain.
AB  - Neurogenesis, the formation of new neurons, can be observed in the adult brain of
      many mammalian species, including humans. Despite significant progress in our
      understanding of adult neurogenesis, we are still missing data about the extent
      and location of production of neural precursors in the adult mammalian brain. We
      used 5-ethynyl-2'-deoxyuridine (EdU) to map the location of proliferating cells
      throughout the entire adult mouse brain and found that neurogenesis occurs at two
      locations in the mouse brain. The larger one we define as the main proliferative
      zone (MPZ), and the smaller one corresponds to the subgranular zone of the
      hippocampus. The MPZ can be divided into three parts. The caudate migratory
      stream (CMS) occupies the middle part of the MPZ. The cable of proliferating
      cells emanating from the most anterior part of the CMS toward the olfactory bulbs
      forms the rostral migratory stream. The thin layer of proliferating cells
      extending posteriorly from the CMS forms the midlayer. We have not found any
      additional aggregations of proliferating cells in the adult mouse brain that
      could suggest the existence of other major neurogenic zones in the adult mouse
      brain. 

PMID- 25375660
TI  - Should we admit that we are powerless over drugs and that our society has become
      unmanageable?

PMID- 25375659
TI  - Risk of echocardiographic pulmonary hypertension in individuals with human
      immunodeficiency virus-hepatitis C virus coinfection.
AB  - RATIONALE: Human immunodeficiency virus (HIV) infection is a risk factor for
      pulmonary hypertension (PH). Chronic hepatitis C virus (HCV) infection may have
      unique or synergistic effects on the pulmonary vasculature, but the prevalence
      and risk factors for PH in HIV-HCV coinfected persons are not known. OBJECTIVES:
      To define the prevalence of echocardiographic PH in a cohort of patients with HIV
      HCV coinfection, to compare this estimate with the reported prevalence of PH
      among those with HIV infection alone, and to identify potential risk factors for
      PH in coinfected individuals. METHODS: We performed a retrospective study of HIV
      HCV coinfected patients followed at our institution from 2003 to 2012 with
      evidence of HCV infection (positive HCV antibody, measurable HCV ribonucleic acid
      viral load, and/or genotype) within 6 months of transthoracic echocardiogram. PH
      was defined by an estimated pulmonary artery systolic pressure (PASP) of greater
      than or equal to 40 mm Hg or more than moderate right ventricular dysfunction. We
      excluded those diagnosed with cirrhosis, left ventricular ejection fraction less
      than 50%, or more than moderate aortic or mitral valve disease. MEASUREMENTS AND
      MAIN RESULTS: Sixty-eight patients were included, and 43 had adequate estimates
      of PASP. The median (interquartile range) age was 52 (48-57) years, and 45 (67%)
      were men. Eight (19%) had PH, and three (7%) had more than moderate right
      ventricular dysfunction. After age and sex adjustment, interferon (IFN)-based HCV
      treatment was associated with higher PASP (beta, 6.00 mm Hg; 95% confidence
      interval, 0.09-11.90; P = 0.047) and with the risk of PH (odds ratio, 5.65; 95%
      confidence interval, 1.07-29.93; P = 0.042). These associations persisted after
      adjustment for comorbidities but were attenuated by adjustment for duration of
      HCV diagnosis. CONCLUSIONS: The prevalence of echocardiographic PH may be higher
      in HIV-HCV coinfected individuals than in those with HIV monoinfection. IFN-based
      HCV treatment and time since HCV diagnosis were associated with the development
      of PH as assessed by echocardiography. Further studies are needed to examine HIV
      HCV coinfection, HCV treatment, and duration of infection as possible causes of
      pulmonary vascular disease.

PMID- 25375662
TI  - Relationship of diabetic retinopathy with coronary artery disease in Asian
      Indians with type 2 diabetes: the Chennai Urban Rural Epidemiology Study (CURES)
      Eye Study--3.
AB  - OBJECTIVES: This study assessed the relationship between diabetic retinopathy
      (DR) and coronary artery diseases (CAD) in Asian Indians, who are known to be at
      high risk of CAD and diabetes but have lower prevalence of DR. SUBJECTS AND
      METHODS: Type 2 diabetes subjects (n=1,736) were selected from the urban
      component of the population-based Chennai Urban Rural Epidemiology Study Eye
      Study. Four-field stereo retinal color photography was done, and DR when present
      was classified according to the Early Treatment Diabetic Retinopathy Study
      grading system. Among the 1,723 subjects with gradable fundus photographs, 12
      lead electrocardiogram (ECG) was performed in 1,602 individuals, and analysis was
      restricted to this group. CAD was diagnosed based on documented medical history
      of CAD or Minnesota coding of ECGs. RESULTS: The prevalence of CAD was
      significantly higher among subjects with DR compared with those without (11.3%
      vs. 6.7%; P=0.007). A significant association was observed between DR and CAD in
      subjects with glycated hemoglobin (HbA1c) levels >7% (P=0.002). After controlling
      for age and gender, only hard exudates were associated with CAD (P=0.032).
      Logistic regression analysis revealed that even after adjusting for age, gender,
      HbA1c, mean arterial blood pressure, smoking, serum cholesterol, triglyceride,
      and low-density lipoprotein cholesterol levels, DR was significantly associated
      with CAD among the study subjects (odds ratio [OR]=1.58; 95% confidence interval
      [CI], 1.00-2.49; P=0.049) and those subjects with duration of diabetes >10 years
      (OR=4.06; 95% CI, 1.55-10.60; P=0.004). CONCLUSIONS: This cross-sectional study
      shows a significant association between DR and CAD in South Indian subjects with
      type 2 diabetes.

PMID- 25375663
TI  - Health care outcomes and advance care planning in older adults who receive home
      based palliative care: a pilot cohort study.
AB  - BACKGROUND: Approximately 20% of seniors live with five or more chronic medical
      illnesses. Terminal stages of their lives are often characterized by repeated
      burdensome hospitalizations and advance care directives are insufficiently
      addressed. This study reports on the preliminary results of a Palliative Care
      Homebound Program (PCHP) at the Mayo Clinic in Rochester, Minnesota to service
      these vulnerable populations. OBJECTIVE: The study objective was to evaluate
      inpatient hospital utilization and the adequacy of advance care planning in
      patients who receive home-based palliative care. METHODS: This is a retrospective
      pilot cohort study of patients enrolled in the PCHP between September 2012 and
      March 2013. Two control patients were matched to each intervention patient by
      propensity scoring methods that factor in risk and prognosis. Primary outcomes
      were six-month hospital utilization including ER visits. Secondary outcomes
      evaluated advance care directive completion and overall mortality. RESULTS:
      Patients enrolled in the PCHP group (n = 54) were matched to 108 controls with an
      average age of 87 years. Ninety-two percent of controls and 33% of PCHP patients
      were admitted to the hospital at least once. The average number of hospital
      admissions was 1.36 per patient for controls versus 0.35 in the PCHP (p < 0.001).
      Total hospital days were reduced by 5.13 days. There was no difference between
      rates of ER visits. Advanced care directive were completed more often in the
      intervention group (98%) as compared to controls (31%), with p < 0.001. Goals of
      care discussions were held at least once for all patients in the PCHP group,
      compared to 41% in the controls.

PMID- 25375661
TI  - Strategies for Increasing Cervical Cancer Screening Amongst First Nations
      Communities in Northwest Ontario, Canada.
AB  - The high burden of cervical cancer in Indigenous populations worldwide is due to
      underscreening and inadequate follow-up. Using qualitative, participatory action
      research, we interviewed health care staff to identify ways to increase screening
      recruitment in First Nations communities in Northwest Ontario, Canada. Our
      findings suggest the value of a multilevel social-ecological model to promote
      behavioral changes at the community, health care service and stakeholder, and
      decision-maker level. Participants emphasized the central role of First Nations
      women as nurturers of life and for the well-being of their family members. They
      stressed the importance of building awareness and motivation for cervical cancer
      screening through various activities including continuous education, hosting
      screening events specifically for women, improving the attitude and service of
      health care providers, and promoting screening tools and policies that complement
      and are respectful of First Nations women. 

PMID- 25375665
TI  - Advances and recent trends in the field of monolithic columns for chromatography.

PMID- 25375664
TI  - Exaggerated pulmonary hypertension and right ventricular dysfunction in high
      altitude dwellers with patent foramen ovale.
AB  - BACKGROUND: There is considerable interindividual variability in pulmonary artery
      pressure among high-altitude (HA) dwellers, but the underlying mechanism is not
      known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of
      the general population. Its prevalence is increased in clinical conditions
      associated with pulmonary hypertension and arterial hypoxemia, and it is thought
      to aggravate these problems. METHODS: We searched for a PFO (transesophageal
      echocardiography) in healthy HA dwellers (n = 22) and patients with chronic
      mountain sickness (n = 35) at 3,600 m above sea level and studied its effects
      (transthoracic echocardiography) on right ventricular (RV) function, pulmonary
      artery pressure, and vascular resistance at rest and during mild exercise (50 W),
      an intervention designed to further increase pulmonary artery pressure. RESULTS:
      The prevalence of PFO (32%) was similar to that reported in low-altitude
      populations and was not different in participants with and without chronic
      mountain sickness. Its presence was associated with RV enlargement at rest and an
      exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25
      +/- 7 mm Hg vs 15 +/- 9 mm Hg, P < .001) and a blunted increase in fractional
      area change of the right ventricle (3% [-1%, 5%] vs 7% [3%, 16%], P = .008)
      during mild exercise. CONCLUSIONS: These findings show, we believe for the first
      time, that although the prevalence of PFO is not increased in HA dwellers, its
      presence appears to facilitate pulmonary vasoconstriction and RV dysfunction
      during a mild physical effort frequently associated with daily activity. TRIAL
      REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

PMID- 25375666
TI  - Atomic scale mechanisms of friction reduction and wear protection by graphene.
AB  - We study nanoindentation and scratching of graphene-covered Pt(111) surfaces in
      computer simulations and experiments. We find elastic response at low load,
      plastic deformation of Pt below the graphene at intermediate load, and eventual
      rupture of the graphene at high load. Friction remains low in the first two
      regimes, but jumps to values also found for bare Pt(111) surfaces upon graphene
      rupture. While graphene substantially enhances the load carrying capacity of the
      Pt substrate, the substrate's intrinsic hardness and friction are recovered upon
      graphene rupture. 

PMID- 25375668
TI  - Assessing the impacts of ethanol and isobutanol on gaseous and particulate
      emissions from flexible fuel vehicles.
AB  - This study investigated the effects of higher ethanol blends and an isobutanol
      blend on the criteria emissions, fuel economy, gaseous toxic pollutants, and
      particulate emissions from two flexible-fuel vehicles equipped with spark
      ignition engines, with one wall-guided direct injection and one port fuel
      injection configuration. Both vehicles were tested over triplicate Federal Test
      Procedure (FTP) and Unified Cycles (UC) using a chassis dynamometer. Emissions of
      nonmethane hydrocarbons (NMHC) and carbon monoxide (CO) showed some statistically
      significant reductions with higher alcohol fuels, while total hydrocarbons (THC)
      and nitrogen oxides (NOx) did not show strong fuel effects. Acetaldehyde
      emissions exhibited sharp increases with higher ethanol blends for both vehicles,
      whereas butyraldehyde emissions showed higher emissions for the butanol blend
      relative to the ethanol blends at a statistically significant level. Particulate
      matter (PM) mass, number, and soot mass emissions showed strong reductions with
      increasing alcohol content in gasoline. Particulate emissions were found to be
      clearly influenced by certain fuel parameters including oxygen content, hydrogen
      content, and aromatics content. 

PMID- 25375667
TI  - Phosphorylation by PINK1 releases the UBL domain and initializes the
      conformational opening of the E3 ubiquitin ligase Parkin.
AB  - Loss-of-function mutations in PINK1 or PARKIN are the most common causes of
      autosomal recessive Parkinson's disease. Both gene products, the Ser/Thr kinase
      PINK1 and the E3 Ubiquitin ligase Parkin, functionally cooperate in a
      mitochondrial quality control pathway. Upon stress, PINK1 activates Parkin and
      enables its translocation to and ubiquitination of damaged mitochondria to
      facilitate their clearance from the cell. Though PINK1-dependent phosphorylation
      of Ser65 is an important initial step, the molecular mechanisms underlying the
      activation of Parkin's enzymatic functions remain unclear. Using molecular
      modeling, we generated a complete structural model of human Parkin at all atom
      resolution. At steady state, the Ub ligase is maintained inactive in a closed,
      auto-inhibited conformation that results from intra-molecular interactions.
      Evidently, Parkin has to undergo major structural rearrangements in order to
      unleash its catalytic activity. As a spark, we have modeled PINK1-dependent Ser65
      phosphorylation in silico and provide the first molecular dynamics simulation of
      Parkin conformations along a sequential unfolding pathway that could release its
      intertwined domains and enable its catalytic activity. We combined free
      (unbiased) molecular dynamics simulation, Monte Carlo algorithms, and minimal
      biasing methods with cell-based high content imaging and biochemical assays.
      Phosphorylation of Ser65 results in widening of a newly defined cleft and
      dissociation of the regulatory N-terminal UBL domain. This motion propagates
      through further opening conformations that allow binding of an Ub-loaded E2 co
      enzyme. Subsequent spatial reorientation of the catalytic centers of both enzymes
      might facilitate the transfer of the Ub moiety to charge Parkin. Our structure
      function study provides the basis to elucidate regulatory mechanisms and activity
      of the neuroprotective Parkin. This may open up new avenues for the development
      of small molecule Parkin activators through targeted drug design. 

PMID- 25375669
TI  - Scalp reconstruction: an algorithmic approach and systematic review.
AB  - IMPORTANCE: Reconstruction of the scalp after acquired defects remains a common
      challenge for the reconstructive surgeon, especially in a patient with a history
      of radiation to the area. OBJECTIVE: To review the current literature and
      describe a novel algorithm to help guide the reconstructive surgeon in
      determining the optimal reconstruction from a cosmetic and functional standpoint.
      Pertinent surgical anatomy, considerations for patient and technique selection,
      reconstructive goals, as well as the reconstructive ladder, are also discussed.
      EVIDENCE REVIEW: A PubMed and Medline search was performed of the entire English
      literature with respect to scalp reconstruction. Priority of review was given to
      those studies with higher-quality levels of evidence. FINDINGS: Size, location,
      radiation history, and potential for hairline distortion are important factors in
      determining the ideal reconstruction. The tighter and looser areas of the scalp
      play a major role in the potential for primary or local flap closure. Patients
      with medium to large defects and a history of radiation will likely benefit from
      free tissue transfer. CONCLUSIONS AND RELEVANCE: Ideal reconstruction of scalp
      defects relies on a comprehensive understanding of scalp anatomy, a full
      consideration of the armamentarium of surgical techniques, and a detailed
      appraisal of patient factors and expectations. The simplest reconstruction should
      be used whenever possible to provide the most functional and aesthetic scalp
      reconstruction, with the least amount of complexity. LEVEL OF EVIDENCE: NA.

PMID- 25375671
TI  - Identification of transcription factor genes and their correlation with the high
      diversity of stramenopiles.
AB  - The biological diversity among Stramenopiles is striking; they range from large
      multicellular seaweeds to tiny unicellular species, they embrace many
      ecologically important autothrophic (e.g., diatoms, brown algae), and
      heterotrophic (e.g., oomycetes) groups. Transcription factors (TFs) and other
      transcription regulators (TRs) regulate spatial and temporal gene expression. A
      plethora of transcriptional regulatory proteins have been identified and
      classified into families on the basis of sequence similarity. The purpose of this
      work is to identify the TF and TR complement in diverse species belonging to
      Stramenopiles in order to understand how these regulators may contribute to their
      observed diversity. We identified and classified 63 TF and TR families in 11
      species of Stramenopiles. In some species we found gene families with high
      relative importance. Taking into account the 63 TF and TR families identified, 28
      TF and TR families were established to be positively correlated with specific
      traits like number of predicted proteins, number of flagella and number of cell
      types during the life cycle. Additionally, we found gains and losses in TF and TR
      families specific to some species and clades, as well as, two families with high
      abundance specific to the autotrophic species and three families with high
      abundance specific to the heterotropic species. For the first time, there is a
      systematic search of TF and TR families in Stramenopiles. The attempts to uncover
      relationships between these families and the complexity of this group may be of
      great impact, considering that there are several important pathogens of plants
      and animals, as well as, important species involved in carbon cycling. Specific
      TF and TR families identified in this work appear to be correlated with
      particular traits in the Stramenopiles group and may be correlated with the high
      complexity and diversity in Stramenopiles. 

PMID- 25375670
TI  - ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP
      SrbA reveals a new regulator of the fungal hypoxia response and virulence.
AB  - The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA
      belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and
      is crucial for antifungal drug resistance and virulence. The latter phenotype is
      especially striking, as loss of SrbA results in complete loss of virulence in
      murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs
      mediate fungal virulence is unknown, though it has been suggested that lack of
      growth in hypoxic conditions accounts for the attenuated virulence. To further
      understand the role of SrbA in fungal infection site pathobiology, chromatin
      immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) was
      used to identify genes under direct SrbA transcriptional regulation in hypoxia.
      These results confirmed the direct regulation of ergosterol biosynthesis and iron
      uptake by SrbA in hypoxia and revealed new roles for SrbA in nitrate assimilation
      and heme biosynthesis. Moreover, functional characterization of an SrbA target
      gene with sequence similarity to SrbA identified a new transcriptional regulator
      of the fungal hypoxia response and virulence, SrbB. SrbB co-regulates genes
      involved in heme biosynthesis and demethylation of C4-sterols with SrbA in
      hypoxic conditions. However, SrbB also has regulatory functions independent of
      SrbA including regulation of carbohydrate metabolism. Loss of SrbB markedly
      attenuates A. fumigatus virulence, and loss of both SREBPs further reduces in
      vivo fungal growth. These data suggest that both A. fumigatus SREBPs are critical
      for hypoxia adaptation and virulence and reveal new insights into SREBPs' complex
      role in infection site adaptation and fungal virulence. 

PMID- 25375676
TI  - Combined experimental and bioinformatics analysis for the prediction and
      identification of VHR/DUSP3 nuclear targets related to DNA damage and repair.
AB  - The atypical dual-specificity phosphatases (aDUSPs) are a group of protein
      tyrosine phosphatases (PTPs) that have been increasingly studied recently, but
      little is known about their substrates or their roles and regulation. aDUSPs are
      typically low-molecular-weight enzymes that are distinct from the mitogen
      activated protein kinase phosphatases (MKPs) but that still function in the
      regulation of the MAPK signalling cascade. aDUSPs may also have non-MAPK
      substrates, based on homologies observed in the sequences flanking potential
      phosphotyrosine target sites of other proteins and the cell type-specific
      characteristics of certain aDUSPs. Here, we combined experimental and
      computational tools to identify new substrates and protein partners of VHR
      (DUSP3) phosphatase in HeLa cells exposed to genotoxic stress. Experimental
      approaches confirmed the good stability of VHR and its nuclear co-localisation
      with classical MAPK substrates. The bioinformatics analysis of 4539 human nuclear
      proteins to identify a subset with functions related to DNA damage response and
      repair or to checkpoints and cell cycle control, that contain the
      phosphorylatable Thr-X-Tyr motif of MAPK with a high probability of dual
      phosphorylation, and that have structural homology to the MAPK activation loop
      resulted in a list of 57 putative VHR substrates. Fluorescence confocal
      microscopy and pull-down experiments followed by immunoblots revealed that VHR co
      localised and interacted with components of the MRN complex and pH2AX, a DNA
      double-strand break sensor. Our platform, which combines experimental data from
      structure-function and bioinformatics analyses based on MAPK substrate
      similarities, provides a low-cost and rapid approach for the identification of
      novel aDUSP-interacting proteins with unknown roles in genotoxic stress response
      and genome stability maintenance. 

PMID- 25375677
TI  - Monitoring arterial pulse waves with synchronous body sensor network.
AB  - A wireless body sensor network for arterial pulse wave (PW) measurements is
      presented and tested with ten subjects. The system is capable of recording both
      mechanical PW contours with sensors made of a low-cost polypropylene-based
      material called electromechanical film (EMFi) and volume pulse signal with
      photoplethysmographic transducers. By using both types of sensors, the PW
      contours can be recorded from various locations. The system combined with
      automatic analysis methods enables to easily analyze the PW contours in order to
      obtain a more comprehensive view on the vascular health. To demonstrate this, two
      parameters used in literature, reflection index and radial augmentation index
      were calculated for the test subjects as a function of time. The results show
      that these parameter values may vary more than 20% in a period of 100 s, which
      suggests that a large number of PWs should be analyzed before making conclusions
      based on the calculated indices. In addition, the effects of the static bias
      force to the mechanical PW signal recorded with the EMFi sensors were studied.
      The PW signal with the maximum amplitude is obtained when the pressure caused by
      the static bias force corresponds to the contact pressure between typical
      systolic and diastolic blood pressures. The EMFi sensors used in the proposed
      system are a potential low-cost alternative for tonometric sensors in collecting
      data in the PW analysis for arterial screening. 

PMID- 25375675
TI  - Estimating HIV-1 fitness characteristics from cross-sectional genotype data.
AB  - Despite the success of highly active antiretroviral therapy (HAART) in the
      management of human immunodeficiency virus (HIV)-1 infection, virological failure
      due to drug resistance development remains a major challenge. Resistant mutants
      display reduced drug susceptibilities, but in the absence of drug, they generally
      have a lower fitness than the wild type, owing to a mutation-incurred cost. The
      interaction between these fitness costs and drug resistance dictates the
      appearance of mutants and influences viral suppression and therapeutic success.
      Assessing in vivo viral fitness is a challenging task and yet one that has
      significant clinical relevance. Here, we present a new computational modelling
      approach for estimating viral fitness that relies on common sparse cross
      sectional clinical data by combining statistical approaches to learn drug
      specific mutational pathways and resistance factors with viral dynamics models to
      represent the host-virus interaction and actions of drug mechanistically. We
      estimate in vivo fitness characteristics of mutant genotypes for two
      antiretroviral drugs, the reverse transcriptase inhibitor zidovudine (ZDV) and
      the protease inhibitor indinavir (IDV). Well-known features of HIV-1 fitness
      landscapes are recovered, both in the absence and presence of drugs. We quantify
      the complex interplay between fitness costs and resistance by computing selective
      advantages for different mutants. Our approach extends naturally to multiple
      drugs and we illustrate this by simulating a dual therapy with ZDV and IDV to
      assess therapy failure. The combined statistical and dynamical modelling approach
      may help in dissecting the effects of fitness costs and resistance with the
      ultimate aim of assisting the choice of salvage therapies after treatment
      failure. 

PMID- 25375678
TI  - Analysis and classification of sleep stages based on difference visibility graphs
      from a single-channel EEG signal.
AB  - The existing sleep stages classification methods are mainly based on time or
      frequency features. This paper classifies the sleep stages based on graph domain
      features from a single-channel electroencephalogram (EEG) signal. First, each
      epoch (30 s) EEG signal is mapped into a visibility graph (VG) and a horizontal
      VG (HVG). Second, a difference VG (DVG) is obtained by subtracting the edges set
      of the HVG from the edges set of the VG to extract essential degree sequences and
      to detect the gait-related movement artifact recordings. The mean degrees (MDs)
      and degree distributions (DDs) P (k) on HVGs and DVGs are analyzed epoch-by-epoch
      from 14,963 segments of EEG signals. Then, the MDs of each DVG and HVG and seven
      distinguishable DD values of P (k) from each DVG are extracted. Finally, nine
      extracted features are forwarded to a support vector machine to classify the
      sleep stages into two, three, four, five, and six states. The accuracy and kappa
      coefficients of six-state classification are 87.5% and 0.81, respectively. It was
      found that the MDs of the VGs on the deep sleep stage are higher than those on
      the awake and light sleep stages, and the MDs of the HVGs are just the reverse.

PMID- 25375679
TI  - Gait and balance analysis for patients with Alzheimer's disease using an inertial
      sensor-based wearable instrument.
AB  - Despite patients with Alzheimer's disease (AD) were reported of revealing gait
      disorders and balance problems, there is still lack of objective quantitative
      measurement of gait patterns and balance capability of AD patients. Based on an
      inertial-sensor-based wearable device, this paper develops gait and balance
      analyzing algorithms to obtain quantitative measurements and explores the
      essential indicators from the measurements for AD diagnosis. The gait analyzing
      algorithm is composed of stride detection followed by gait cycle decomposition so
      that gait parameters are developed from the decomposed gait details. On the other
      hand, the balance is measured by the sway speed in anterior-posterior (AP) and
      medial-lateral (ML) directions of the projection path of body's center of mass
      (COM). These devised gait and balance parameters were explored on twenty-one AD
      patients and fifty healthy controls (HCs). Special evaluation procedure including
      single-task and dual-task walking experiments for observing the cognitive
      function and attention is also devised for the comparison of AD and HC groups.
      Experimental results show that the wearable instrument with the designed gait and
      balance analyzing system is a promising tool for automatically analyzing gait
      information and balance ability, serving as assistant indicators for early
      diagnosis of AD. 

PMID- 25375680
TI  - Detection of wrinkle frames in endoluminal videos using betweenness centrality
      measures for images.
AB  - Intestinal contractions are one of the most important events to diagnose motility
      pathologies of the small intestine. When visualized by wireless capsule endoscopy
      (WCE), the sequence of frames that represents a contraction is characterized by a
      clear wrinkle structure in the central frames that corresponds to the folding of
      the intestinal wall. In this paper, we present a new method to robustly detect
      wrinkle frames in full WCE videos by using a new mid-level image descriptor that
      is based on a centrality measure proposed for graphs. We present an extended
      validation, carried out in a very large database, that shows that the proposed
      method achieves state-of-the-art performance for this task. 

PMID- 25375681
TI  - A smartphone-centric system for the range of motion assessment in stroke
      patients.
AB  - The range of motion (ROM) in stroke patients is often severely affected.
      Poststroke rehabilitation is guided through the use of clinical assessment scales
      for the rROM. Unfortunately, these scales are not widely utilized in clinical
      practice as they are excessively time-consuming. Although commercial motion
      capture systems are capable of providing the information required for the
      assessments, most systems are either too costly or lack the convenience required
      for assessments to be conducted on a daily basis. This paper presents the design
      and implementation of a smartphone-based system for automated motor assessment
      using low-cost off-the-shelf inertial sensors. The system was used to automate a
      portion of the upper-extremity Fugl-Meyer assessment (FMA), which is widely used
      to quantify motor deficits in stroke survivors. Twelve out of 33 items were
      selected, focusing mainly on joint angle measurements of the upper body. The
      system has the ability to automatically identify the assessment item being
      conducted, and calculate the maximum respective joint angle achieved. Preliminary
      results show the ability of this system to achieve comparable results to
      goniometer measurements, while significantly reducing the time required to
      conduct the assessments. The portability and ease-of-use of the system would
      simplify the task of conducting range-of-motion assessments. 

PMID- 25375682
TI  - Reliable and energy-efficient communications for wireless biomedical implant
      systems.
AB  - Implant devices are used to measure biological parameters and transmit their
      results to remote off-body devices. As implants are characterized by strict
      requirements on size, reliability, and power consumption, applying the concept of
      cooperative communications to wireless body area networks offers several
      benefits. In this paper, we aim to minimize the power consumption of the implant
      device by utilizing on-body wearable devices, while providing the necessary
      reliability in terms of outage probability and bit error rate. Taking into
      account realistic power considerations and wireless propagation environments
      based on the IEEE P802.l5 channel model, an exact theoretical analysis is
      conducted for evaluating several communication scenarios with respect to the
      position of the wearable device and the motion of the human body. The derived
      closed-form expressions are employed toward minimizing the required transmission
      power, subject to a minimum quality-of-service requirement. In this way, the
      complexity and power consumption are transferred from the implant device to the
      on-body relay, which is an efficient approach since they can be easily replaced,
      in contrast to the in-body implants. 

PMID- 25375683
TI  - Development of mHealth applications for pre-eclampsia triage.
AB  - The development of mobile applications for the diagnosis and management of
      pregnant women with pre-eclampsia is described. These applications are designed
      for use by community-based health care providers (c-HCPs) in health facilities
      and during home visits to collect symptoms and perform clinical measurements
      (including pulse oximeter readings). The clinical data collected in women with
      pre-eclampsia are used as the inputs to a predictive model providing a risk score
      for the development of adverse outcomes. Based on this risk, the applications
      provide recommendations on treatment, referral, and reassessment. c-HCPs can
      access patient records across multiple visits, using multiple devices that are
      synchronized using a secure Research Electronic Data Capture server. A unique
      feature of these applications is the ability to measure oxygen saturation with a
      pulse oximeter connected to a smartphone (Phone Oximeter). The mobile health
      application development process, including challenges encountered and solutions
      are described. 

PMID- 25375684
TI  - Electrodermal activity in bipolar patients during affective elicitation.
AB  - Bipolar patients are characterized by a pathological unpredictable behavior,
      resulting in fluctuations between states of depression and episodes of mania or
      hypomania. In the current clinical practice, the psychiatric diagnosis is made
      through clinician-administered rating scales and questionnaires, disregarding the
      potential contribution provided by physiological signs. The aim of this paper is
      to investigate how changes in the autonomic nervous system activity can be
      correlated with clinical mood swings. More specifically, a group of ten bipolar
      patients underwent an emotional elicitation protocol to investigate the autonomic
      nervous system dynamics, through the electrodermal activity (EDA), among
      different mood states. In addition, a control group of ten healthy subjects were
      recruited and underwent the same protocol. Physiological signals were analyzed by
      applying the deconvolutive method to reconstruct EDA tonic and phasic components,
      from which several significant features were extracted to quantify the
      sympathetic activation. Experimental results performed on both the healthy
      subjects and the bipolar patients supported the hypothesis of a relationship
      between autonomic dysfunctions and pathological mood states. 

PMID- 25375685
TI  - Distributed, signal strength-based indoor localization algorithm for use in
      healthcare environments.
AB  - In current healthcare environments, a trend toward mobile and personalized
      interactions between people and nurse call systems is strongly noticeable.
      Therefore, it should be possible to locate patients at all times and in all
      places throughout the care facility. This paper aims at describing a method by
      which a mobile node can locate itself indoors, based on signal strength
      measurements and a minimal amount of yes/no decisions. The algorithm has been
      developed specifically for use in a healthcare environment. With extensive
      testing and statistical support, we prove that our algorithm can be used in a
      healthcare setting with an envisioned level of localization accuracy up to room
      revel (or region level in a corridor), while avoiding heavy investments since the
      hardware of an existing nurse call network can be reused. The approach opted for
      leads to very high scalability, since thousands of mobile nodes can locate
      themselves. Network timing issues and localization update delays are avoided,
      which ensures that a patient can receive the needed care in a time and resources
      efficient way. 

PMID- 25375686
TI  - Risk scoring for prediction of acute cardiac complications from imbalanced
      clinical data.
AB  - Fast and accurate risk stratification is essential in the emergency department
      (ED) as it allows clinicians to identify chest pain patients who are at high risk
      of cardiac complications and require intensive monitoring and early intervention.
      In this paper, we present a novel intelligent scoring system using heart rate
      variability, 12-lead electrocardiogram (ECG), and vital signs where a hybrid
      sampling-based ensemble learning strategy is proposed to handle data imbalance.
      The experiments were conducted on a dataset consisting of 564 chest pain patients
      recruited at the ED of a tertiary hospital. The proposed ensemble-based scoring
      system was compared with established scoring methods such as the modified early
      warning score and the thrombolysis in myocardial infarction score, and showed its
      effectiveness in predicting acute cardiac complications within 72 h in terms of
      the receiver operation characteristic analysis.

PMID- 25375687
TI  - A syntactic two-component encoding model for the trajectories of human actions.
AB  - Human actions have been widely studied for their potential application in various
      areas such as sports, pervasive patient monitoring, and rehabilitation. However,
      challenges still persist pertaining to determining the most useful ways to
      describe human actions at the sensor, then limb and complete action levels of
      representation and deriving important relations between these levels each
      involving their own atomic components. In this paper, we report on a motion
      encoder developed for the sensor level based on the need to distinguish between
      the shape of the sensor's trajectory and its temporal characteristics during
      execution. This distinction is critical as it provides a different encoding
      scheme than the usual velocity and acceleration measures which confound these two
      attributes of any motion. At the same time, we eliminate noise from sensors by
      comparing temporal and spatial indexing schemes and a number of optimal filtering
      models for robust encoding. Results demonstrate the benefits of spatial indexing
      and separating the shape and dynamics of a motion, as well as its ability to
      decompose complex motions into several atomic ones. Finally, we discuss how this
      specific type of sensor encoder bears on the derivation of limb and complete
      action descriptions. 

PMID- 25375688
TI  - Depth-based human fall detection via shape features and improved extreme learning
      machine.
AB  - Falls are one of the major causes leading to injury of elderly people. Using
      wearable devices for fall detection has a high cost and may cause inconvenience
      to the daily lives of the elderly. In this paper, we present an automated fall
      detection approach that requires only a low-cost depth camera. Our approach
      combines two computer vision techniques-shape-based fall characterization and a
      learning-based classifier to distinguish falls from other daily actions. Given a
      fall video clip, we extract curvature scale space (CSS) features of human
      silhouettes at each frame and represent the action by a bag of CSS words (BoCSS).
      Then, we utilize the extreme learning machine (ELM) classifier to identify the
      BoCSS representation of a fall from those of other actions. In order to eliminate
      the sensitivity of ELM to its hyperparameters, we present a variable-length
      particle swarm optimization algorithm to optimize the number of hidden neurons,
      corresponding input weights, and biases of ELM. Using a low-cost Kinect depth
      camera, we build an action dataset that consists of six types of actions
      (falling, bending, sitting, squatting, walking, and lying) from ten subjects.
      Experimenting with the dataset shows that our approach can achieve up to 91.15%
      sensitivity, 77.14% specificity, and 86.83% accuracy. On a public dataset, our
      approach performs comparably to state-of-the-art fall detection methods that need
      multiple cameras. 

PMID- 25375689
TI  - Multiscale roughness approach for assessing posterior capsule opacification.
AB  - Posterior capsule opacification (PCO) is a common complication in patients who
      have undergone cataract surgery, occurring in up to 50% of patients by two to
      three years after the operation. Assessment of PCO has been mainly subjective,
      making it difficult to understand its progression over time or assess the
      effectiveness of strategies used for the prevention of PCO. Fully automated PCO
      assessment systems developed so far offer objective grades. However, they do not
      provide morphological PCO data useful for an effective analysis of scores. This
      paper proposes a novel method based on multiscale roughness estimation to detect
      and quantify the PCO areas. This method is also characterized by its robustness
      against monotonic illumination variations. Extensive experimentation showcases a
      distinctive analysis and assessment power of our method compared to other
      competitive methods. The results show a high correlation of 84.6% with respect to
      clinical scores. 

PMID- 25375690
TI  - An innovative nonintrusive driver assistance system for vital signal monitoring.
AB  - This paper describes an in-vehicle nonintrusive biopotential measurement system
      for driver health monitoring and fatigue detection. Previous research has found
      that the physiological signals including eye features, electrocardiography (ECG),
      electroencephalography (EEG) and their secondary parameters such as heart rate
      and HR variability are good indicators of health state as well as driver fatigue.
      A conventional biopotential measurement system requires the electrodes to be in
      contact with human body. This not only interferes with the driver operation, but
      also is not feasible for long-term monitoring purpose. The driver assistance
      system in this paper can remotely detect the biopotential signals with no
      physical contact with human skin. With delicate sensor and electronic design,
      ECG, EEG, and eye blinking can be measured. Experiments were conducted on a high
      fidelity driving simulator to validate the system performance. The system was
      found to be able to detect the ECG/EEG signals through cloth or hair with no
      contact with skin. Eye blinking activities can also be detected at a distance of
      10 cm. Digital signal processing algorithms were developed to decimate the signal
      noise and extract the physiological features. The extracted features from the
      vital signals were further analyzed to assess the potential criterion for
      alertness and drowsiness determination. 

PMID- 25375691
TI  - Editorial: PRX takes on a new role.

PMID- 25375692
TI  - Optical simulation of neutrino oscillations in binary waveguide arrays.
AB  - We theoretically propose and investigate an optical analogue of neutrino
      oscillations in a pair of vertically displaced binary waveguide arrays with
      longitudinally modulated effective refractive index. Optical propagation is
      modeled through coupled-mode equations, which in the continuous limit converge to
      two coupled Dirac equations for fermionic particles with different mass states,
      analogously to neutrinos. In addition to simulating neutrino oscillation in the
      noninteracting regime, our optical setting enables us to explore neutrino
      interactions in extreme regimes that are expected to play an important role in
      massive supernova stars. In particular, we predict the quenching of neutrino
      oscillations and the existence of topological defects, i.e., neutrino solitons,
      which in our photonic simulator should be observable as excitation of optical gap
      solitons propagating along the binary arrays at high excitation intensities. 

PMID- 25375693
TI  - Catalytic coherence.
AB  - Because of conservation of energy we cannot directly turn a quantum system with a
      definite energy into a superposition of different energies. However, if we have
      access to an additional resource in terms of a system with a high degree of
      coherence, as for standard models of laser light, we can overcome this
      limitation. The question is to what extent coherence gets degraded when utilized.
      Here it is shown that coherence can be turned into a catalyst, meaning that we
      can use it repeatedly without ever diminishing its power to enable coherent
      operations. This finding stands in contrast to the degradation of other quantum
      resources and has direct consequences for quantum thermodynamics, as it shows
      that latent energy that may be locked into superpositions of energy eigenstates
      can be released catalytically. 

PMID- 25375694
TI  - Hierarchy of stochastic pure states for open quantum system dynamics.
AB  - We derive a hierarchy of stochastic evolution equations for pure states (quantum
      trajectories) for open quantum system dynamics with non-Markovian structured
      environments. This hierarchy of pure states (HOPS) is generally applicable and
      provides the exact reduced density operator as an ensemble average over
      normalized states. The corresponding nonlinear equations are presented. We
      demonstrate that HOPS provides an efficient theoretical tool and apply it to the
      spin-boson model, the calculation of absorption spectra of molecular aggregates,
      and energy transfer in a photosynthetic pigment-protein complex. 

PMID- 25375695
TI  - Area law scaling for the entropy of disordered quasifree fermions.
AB  - We study theoretically and numerically the entanglement entropy of the d
      dimensional free fermions whose one-body Hamiltonian is the Anderson model. Using
      the basic facts of the exponential Anderson localization, we show first that the
      disorder averaged entanglement entropy ?S(Lambda)? of the d dimension cube Lambda
      of side length l admits the area law scaling ?S(Lambda)? ~ l((d-1)),l ? 1, even
      in the gapless case, thereby manifesting the area law in the mean for our model.
      For d = 1 and l ? 1 we obtain then asymptotic bounds for the entanglement entropy
      of typical realizations of disorder and use them to show that the entanglement
      entropy is not self-averaging, i.e., has nonvanishing random fluctuations even if
      l ? 1.

PMID- 25375696
TI  - High-fidelity single-qubit gates for two-electron spin qubits in GaAs.
AB  - Single-qubit operations on singlet-triplet qubits in GaAs double quantum dots
      have not yet reached the fidelities required for fault-tolerant quantum
      information processing. Considering experimentally important constraints and
      using measured noise spectra, we numerically minimize the effect of decoherence
      (including high-frequency 1/f-like noise) and show, theoretically, that quantum
      gates with fidelities higher than 99.9% are achievable. We also present a self
      consistent tuning protocol which should allow the elimination of individual
      systematic gate errors directly in an experiment. 

PMID- 25375697
TI  - Simple model of complete precessing black-hole-binary gravitational waveforms.
AB  - The construction of a model of the gravitational-wave (GW) signal from generic
      configurations of spinning-black-hole binaries, through inspiral, merger, and
      ringdown, is one of the most pressing theoretical problems in the buildup to the
      era of GW astronomy. We present the first such model in the frequency domain,
      PhenomP, which captures the basic phenomenology of the seven-dimensional
      parameter space of binary configurations with only three key physical parameters.
      Two of these (the binary's mass ratio and an effective total spin parallel to the
      orbital angular momentum, which determines the inspiral rate) define an
      underlying nonprecessing-binary model. The nonprecessing-binary waveforms are
      then twisted up with approximate expressions for the precessional motion, which
      require only one additional physical parameter, an effective precession spin,
      chi(p). All other parameters (total mass, sky location, orientation and
      polarization, and initial phase) can be specified trivially. The model is
      constructed in the frequency domain, which will be essential for efficient GW
      searches and source measurements. We have tested the model's fidelity for GW
      applications by comparison against hybrid post-Newtonian-numerical-relativity
      waveforms at a variety of configurations--although we did not use these numerical
      simulations in the construction of the model. Our model can be used to develop GW
      searches, to study the implications for astrophysical measurements, and as a
      simple conceptual framework to form the basis of generic-binary waveform modeling
      in the advanced-detector era.

PMID- 25375699
TI  - Searching for topological defect dark matter via nongravitational signatures.
AB  - We propose schemes for the detection of topological defect dark matter using
      pulsars and other luminous extraterrestrial systems via nongravitational
      signatures. The dark matter field, which makes up a defect, may interact with
      standard model particles, including quarks and the photon, resulting in the
      alteration of their masses. When a topological defect passes through a pulsar,
      its mass, radius, and internal structure may be altered, resulting in a pulsar
      "quake." A topological defect may also function as a cosmic dielectric material
      with a distinctive frequency-dependent index of refraction, which would give rise
      to the time delay of a periodic extraterrestrial light or radio signal, and the
      dispersion of a light or radio source in a manner distinct to a gravitational
      lens. A topological defect passing through Earth may alter Earth's period of
      rotation and give rise to temporary nonzero electric dipole moments for an
      electron, proton, neutron, nuclei and atoms. 

PMID- 25375698
TI  - Narrowing the filter-cavity bandwidth in gravitational-wave detectors via
      optomechanical interaction.
AB  - We propose using optomechanical interaction to narrow the bandwidth of filter
      cavities for achieving frequency-dependent squeezing in advanced gravitational
      wave detectors, inspired by the idea of optomechanically induced transparency.
      This can allow us to achieve a cavity bandwidth on the order of 100 Hz using
      small-scale cavities. Additionally, in contrast to a passive Fabry-Perot cavity,
      the resulting cavity bandwidth can be dynamically tuned, which is useful for
      adaptively optimizing the detector sensitivity when switching amongst different
      operational modes. The experimental challenge for its implementation is a
      stringent requirement for very low thermal noise of the mechanical oscillator,
      which would need a superb mechanical quality factor and a very low temperature.
      We consider one possible setup to relieve this requirement by using optical
      dilution to enhance the mechanical quality factor.

PMID- 25375700
TI  - Galactic center gamma-ray excess from dark matter annihilation: is there a black
      hole spike?
AB  - If the supermassive black hole Sgr A* at the center of the Milky Way grew
      adiabatically from an initial seed embedded in a Navarro-Frenk-White dark matter
      (DM) halo, then the DM profile near the hole has steepened into a spike. We
      calculate the dramatic enhancement to the gamma-ray flux from the Galactic center
      (GC) from such a spike if the 1-3 GeV excess observed in Fermi data is due to DM
      annihilations. We find that for the parameter values favored in recent fits, the
      point-source-like flux from the spike is 35 times greater than the flux from the
      inner 1 degrees  of the halo, far exceeding all Fermi point source detections
      near the GC. We consider the dependence of the spike signal on astrophysical and
      particle parameters and conclude that if the GC excess is due to DM, then a
      canonical adiabatic spike is disfavored by the data. We discuss alternative
      Galactic histories that predict different spike signals, including (i) the
      nonadiabatic growth of the black hole, possibly associated with halo and/or black
      hole mergers, (ii) gravitational interaction of DM with baryons in the dense
      core, such as heating by stars, or (iii) DM self-interactions. We emphasize that
      the spike signal is sensitive to a different combination of particle parameters
      than the halo signal and that the inclusion of a spike component to any DM signal
      in future analyses would provide novel information about both the history of the
      GC and the particle physics of DM annihilations.

PMID- 25375702
TI  - Bounds on invisible Higgs boson decays extracted from LHC ttH production data.
AB  - We present an upper bound on the branching fraction of the Higgs boson to
      invisible particles by recasting a CMS Collaboration search for stop quarks
      decaying to tt + E(T)(miss). The observed (expected) bound, BF(H -> inv.) <
      0.40(0.65) at 95% C.L., is the strongest direct limit to date, benefiting from a
      downward fluctuation in the CMS data in that channel. In addition, we combine
      this new constraint with existing published constraints to give an observed
      (expected) bound of BF(H -> inv.) < 0.40(0.40) at 95% C.L., and we show some of
      the implications for theories of dark matter which communicate through the Higgs
      portal.

PMID- 25375703
TI  - T-odd asymmetry in W + jet events at the LHC.
AB  - W bosons produced at high transverse momentum in hadron collisions can have
      polarization along the direction perpendicular to the production plane, which is
      odd under naive T reversal where both the three-momenta and angular momenta are
      reversed. Perturbative QCD predicts nonzero polarization at the one-loop level,
      which can be measured as parity-odd components in the angular distribution of
      charged leptons from the decay of W bosons. We perform a detector-level
      simulation with the generator MadGraph5_aMC@NLO, and demonstrate that the
      asymmetry can be observed at the 8 TeV LHC with 20 fb(-1) of data. If confirmed,
      it will be the first experimental measurement of the sign of the imaginary part
      of one-loop QCD amplitudes.

PMID- 25375704
TI  - Lattice QCD phase diagram in and away from the strong coupling limit.
AB  - We study lattice QCD with four flavors of staggered quarks. In the limit of
      infinite gauge coupling, "dual" variables can be introduced, which render the
      finite-density sign problem mild and allow a full determination of the MU-T phase
      diagram by Monte Carlo simulations, also in the chiral limit. However, the
      continuum limit coincides with the weak coupling limit. We propose a strong
      coupling expansion approach towards the continuum limit. We show first results,
      including the phase diagram and its chiral critical point, from this expansion
      truncated at next-to-leading order. 

PMID- 25375707
TI  - Helium-droplet-assisted preparation of cold RbSr molecules.
AB  - We present a combined experimental and theoretical study of the RbSr molecule.
      The experimental approach is based on the formation of RbSr molecules on helium
      nanodroplets. Utilizing two-photon ionization spectroscopy, an excitation
      spectrum ranging from 11,600 up to 23,000 cm(-1) was recorded. High level ab
      initio calculations of potential energy curves and transition dipole moments
      accompany the experiment and facilitate an assignment of transitions. We show
      that RbSr molecules desorb from the helium droplets upon excitation, which
      enables dispersed fluorescence spectroscopy of free RbSr. These spectra elucidate
      X(2)Sigma(+) ground and excited state properties. Emission spectra originating
      from states corresponding to the Rb(5s(2)S) + Sr(5s5p(3)P) asymptote were
      recorded; spin-orbit coupling was included for the simulation. The results should
      provide a good basis for achieving the formation of this molecule in cold
      collisions, thus offering intriguing prospects for ultracold molecular physics.

PMID- 25375709
TI  - Second-quantized surface hopping.
AB  - The trajectory surface hopping method for quantum dynamics is reformulated in the
      space of many-particle states to include entanglement and correlation of
      trajectories. Used to describe many-body correlation effects in electronic
      structure theories, second quantization is applied to semiclassical trajectories.
      The new method allows coupling between individual trajectories via energy flow
      and common phase evolution. It captures the properties of a wave packet, such as
      branching, Heisenberg uncertainty, and decoherence. Applied to a superexchange
      process, the method shows very accurate results, comparable to exact quantum data
      and improving greatly on the standard approach. 

PMID- 25375710
TI  - Creating high-harmonic beams with controlled orbital angular momentum.
AB  - A beam with an angular-dependant phase Phi = lphi about the beam axis carries an
      orbital angular momentum of lh per photon. Such beams are exploited to provide
      superresolution in microscopy. Creating extreme ultraviolet or soft-x-ray beams
      with controllable orbital angular momentum is a critical step towards extending
      superresolution to much higher spatial resolution. We show that orbital angular
      momentum is conserved during high-harmonic generation. Experimentally, we use a
      fundamental beam with |l| = 1 and interferometrically determine that the
      harmonics each have orbital angular momentum equal to their harmonic number.
      Theoretically, we show how any small value of orbital angular momentum can be
      coupled to any harmonic in a controlled manner. Our results open a route to
      microscopy on the molecular, or even submolecular, scale.

PMID- 25375711
TI  - Synchronization of two ensembles of atoms.
AB  - We propose a system for observing the correlated phase dynamics of two mesoscopic
      ensembles of atoms through their collective coupling to an optical cavity. We
      find a dynamical quantum phase transition induced by pump noise and cavity output
      coupling. The spectral properties of the superradiant light emitted from the
      cavity show that at a critical pump rate the system undergoes a transition from
      the behavior of two independent oscillators to the phase locking that is the
      signature of quantum synchronization. 

PMID- 25375708
TI  - Reabsorption of soft x-ray emission at high x-ray free-electron laser fluences.
AB  - We report on oxygen K-edge soft x-ray emission spectroscopy from a liquid water
      jet at the Linac Coherent Light Source. We observe significant changes in the
      spectral content when tuning over a wide range of incident x-ray fluences. In
      addition the total emission yield decreases at high fluences. These modifications
      result from reabsorption of x-ray emission by valence-excited molecules generated
      by the Auger cascade. Our observations have major implications for future x-ray
      emission studies at intense x-ray sources. We highlight the importance of the x
      ray pulse length with respect to the core-hole lifetime. 

PMID- 25375706
TI  - Strangeness suppression of qq creation observed in exclusive reactions.
AB  - We measured the ratios of electroproduction cross sections from a proton target
      for three exclusive meson-baryon final states: LambdaK(+), ppi(0), and npi(+),
      with the CLAS detector at Jefferson Lab. Using a simple model of quark
      hadronization, we extract qq creation probabilities for the first time in
      exclusive two-body production, in which only a single qq pair is created. We
      observe a sizable suppression of strange quark-antiquark pairs compared to
      nonstrange pairs, similar to that seen in high-energy production.

PMID- 25375712
TI  - Controlling turbulence in present and future stellarators.
AB  - Turbulence is widely expected to limit the confinement and, thus, the overall
      performance of modern neoclassically optimized stellarators. We employ novel
      petaflop-scale gyrokinetic simulations to predict the distribution of turbulence
      fluctuations and the related transport scaling on entire stellarator magnetic
      surfaces and reveal striking differences to tokamaks. Using a stochastic global
      search optimization method, we derive the first turbulence-optimized stellarator
      configuration stemming from an existing quasiomnigenous design. 

PMID- 25375713
TI  - Backward wave cyclotron-maser emission in the auroral magnetosphere.
AB  - In this Letter, we present theory and particle-in-cell simulations describing
      cyclotron radio emission from Earth's auroral region and similar phenomena in
      other astrophysical environments. In particular, we find that the radiation,
      generated by a down-going electron horseshoe distribution is due to a backward
      wave cyclotron-maser emission process. The backward wave nature of the radiation
      contributes to upward refraction of the radiation that is also enhanced by a
      density inhomogeneity. We also show that the radiation is preferentially
      amplified along the auroral oval rather than transversely. The results are in
      agreement with recent Cluster observations. 

PMID- 25375714
TI  - Experimental demonstration of fusion-relevant conditions in magnetized liner
      inertial fusion.
AB  - This Letter presents results from the first fully integrated experiments testing
      the magnetized liner inertial fusion concept [S. A. Slutz et al., Phys. Plasmas
      17, 056303 (2010)], in which a cylinder of deuterium gas with a preimposed 10
      Taxial magnetic field is heated by Z beamlet, a 2.5 kJ, 1 TW laser, and
      magnetically imploded by a 19 MA, 100 ns rise time current on the Z facility.
      Despite a predicted peak implosion velocity of only 70 km = s, the fuel reaches a
      stagnation temperature of approximately 3 keV, with T(e) ~ T(i), and produces up
      to 2 ?x 10(12) thermonuclear deuterium-deuterium neutrons. X-ray emission
      indicates a hot fuel region with full width at half maximum ranging from 60 to
      120 MUm over a 6 mm height and lasting approximately 2 ns. Greater than 10(10)
      secondary deuterium-tritium neutrons were observed, indicating significant fuel
      magnetization given that the estimated radial areal density of the plasma is only
      2 mg = cm(2).

PMID- 25375716
TI  - Formation of hard power laws in the energetic particle spectra resulting from
      relativistic magnetic reconnection.
AB  - Using fully kinetic simulations, we demonstrate that magnetic reconnection in
      relativistic plasmas is highly efficient at accelerating particles through a
      first-order Fermi process resulting from the curvature drift of particles in the
      direction of the electric field induced by the relativistic flows. This mechanism
      gives rise to the formation of hard power-law spectra in parameter regimes where
      the energy density in the reconnecting field exceeds the rest mass energy density
      sigma = B(2)/(4pinm(e)c(2))>1 and when the system size is sufficiently large. In
      the limit sigma ? 1, the spectral index approaches p = 1 and most of the
      available energy is converted into nonthermal particles. A simple analytic model
      is proposed which explains these key features and predicts a general condition
      under which hard power-law spectra will be generated from magnetic reconnection.

PMID- 25375715
TI  - Understanding fuel magnetization and mix using secondary nuclear reactions in
      magneto-inertial fusion.
AB  - Magnetizing the fuel in inertial confinement fusion relaxes ignition requirements
      by reducing thermal conductivity and changing the physics of burn product
      confinement. Diagnosing the level of fuel magnetization during burn is critical
      to understanding target performance in magneto-inertial fusion (MIF) implosions.
      In pure deuterium fusion plasma, 1.01 MeV tritons are emitted during deuterium
      deuterium fusion and can undergo secondary deuterium-tritium reactions before
      exiting the fuel. Increasing the fuel magnetization elongates the path lengths
      through the fuel of some of the tritons, enhancing their probability of reaction.
      Based on this feature, a method to diagnose fuel magnetization using the ratio of
      overall deuterium-tritium to deuterium-deuterium neutron yields is developed.
      Analysis of anisotropies in the secondary neutron energy spectra further
      constrain the measurement. Secondary reactions also are shown to provide an upper
      bound for the volumetric fuel-pusher mix in MIF. The analysis is applied to
      recent MIF experiments [M. R. Gomez et al., Phys. Rev. Lett. 113, 155003 (2014)]
      on the Z Pulsed Power Facility, indicating that significant magnetic confinement
      of charged burn products was achieved and suggesting a relatively low-mix
      environment. Both of these are essential features of future ignition-scale MIF
      designs.

PMID- 25375717
TI  - Fast and accurate quantum molecular dynamics of dense plasmas across temperature
      regimes.
AB  - We develop and implement a new quantum molecular dynamics approximation that
      allows fast and accurate simulations of dense plasmas from cold to hot
      conditions. The method is based on a carefully designed orbital-free
      implementation of density functional theory. The results for hydrogen and
      aluminum are in very good agreement with Kohn-Sham (orbital-based) density
      functional theory and path integral Monte Carlo calculations for microscopic
      features such as the electron density as well as the equation of state. The
      present approach does not scale with temperature and hence extends to higher
      temperatures than is accessible in the Kohn-Sham method and lower temperatures
      than is accessible by path integral Monte Carlo calculations, while being
      significantly less computationally expensive than either of those two methods.

PMID- 25375718
TI  - Topological growing of Laughlin states in synthetic gauge fields.
AB  - We suggest a scheme for the preparation of highly correlated Laughlin states in
      the presence of synthetic gauge fields, realizing an analogue of the fractional
      quantum Hall effect in photonic or atomic systems of interacting bosons. It is
      based on the idea of growing such states by adding weakly interacting composite
      fermions along with magnetic flux quanta one by one. The topologically protected
      Thouless pump ("Laughlin's argument") is used to create two localized flux quanta
      and the resulting hole excitation is subsequently filled by a single boson,
      which, together with one of the flux quanta, forms a composite fermion. Using our
      protocol, filling 1/2 Laughlin states can be grown with particle number N
      increasing linearly in time and strongly suppressed number fluctuations. To
      demonstrate the feasibility of our scheme, we consider two-dimensional lattices
      subject to effective magnetic fields and strong on-site interactions. We present
      numerical simulations of small lattice systems and also discuss the influence of
      losses. 

PMID- 25375719
TI  - Coherent magnon optics in a ferromagnetic spinor Bose-Einstein condensate.
AB  - We measure the dispersion relation, gap, and magnetic moment of a magnon in the
      ferromagnetic F = 1 spinor Bose-Einstein condensate of (87)Rb. From the
      dispersion relation we measure an average effective mass 1.033(2)(stat)(10)(sys)
      times the atomic mass, as determined by interfering standing and running coherent
      magnon waves within the dense and trapped condensed gas. The measured mass is
      higher than theoretical predictions of mean-field and beyond-mean-field Beliaev
      theory for a bulk spinor Bose gas with s-wave contact interactions. We observe a
      magnon energy gap of h * 2.5(1)(stat)(2)(sys) Hz, which is consistent with the
      predicted effect of magnetic dipole-dipole interactions. These dipolar
      interactions may also account for the high magnon mass. The effective magnetic
      moment of -1.04(2)(stat)(8)(sys) times the atomic magnetic moment is consistent
      with mean-field theory.

PMID- 25375720
TI  - Strong interaction effects and criticality of bosons in shaken optical lattices.
AB  - We study the quantum phase transitions and identify a tricritical point between a
      normal Bose superfluid, a superfluid that breaks additional Z(2) Ising symmetry,
      and a Mott insulator in a recent shaken optical lattice experiment. We show that
      near the transition between normal and Z(2) symmetry breaking superfluids, bosons
      can condense into a momentum state with high or even locally maximum kinetic
      energies due to the interaction effect. We present a general low-energy effective
      field theory that treats both the superfluid transition and the Ising transition
      in a uniform framework. Using the perturbative renormalization group method, we
      find that the critical behavior of the quantum phase transition belongs to a
      universality class different from that of a dilute Bose gas.

PMID- 25375721
TI  - Direct observation of dopant atom diffusion in a bulk semiconductor crystal
      enhanced by a large size mismatch.
AB  - Diffusion is one of the fundamental processes that govern the structure,
      processing, and properties of materials and it plays a crucial role in
      determining device lifetimes. However, direct observations of diffusion processes
      have been elusive and limited only to the surfaces of materials. Here we use an
      aberration-corrected electron microscope to locally excite and directly image the
      diffusion of single Ce and Mn dopants inside bulk wurtzite-type AlN single
      crystals, identifying correlated vacancy-dopant and interstitial-dopant kick-out
      mechanisms. Using a 200 kV electron beam to supply energy, we observe a higher
      frequency of dopant jumps for the larger and heavier Ce atoms than the smaller Mn
      atoms. These observations confirm density-functional-theory-based predictions of
      a decrease in diffusion barrier for large substitutional atoms. The results show
      that combining depth sensitive microscopy with theoretical calculations
      represents a new methodology to investigate diffusion mechanisms, not restricted
      to surface phenomena, but within bulk materials.

PMID- 25375722
TI  - Explosive electric breakdown due to conducting-particle deposition on an
      insulating substrate.
AB  - We introduce a theoretical model to investigate the electric breakdown of a
      substrate on which highly conducting particles are adsorbed and desorbed with a
      probability that depends on the local electric field. We find that, by tuning the
      relative strength q of this dependence, the breakdown can change from continuous
      to explosive. Precisely, in the limit in which the adsorption probability is the
      same for any finite voltage drop, we can map our model exactly onto the q-state
      Potts model and thus the transition to a jump occurs at q = 4. In another limit,
      where the adsorption probability becomes independent of the local field strength,
      the traditional bond percolation model is recovered. Our model is thus an example
      of a possible experimental realization exhibiting a truly discontinuous
      percolation transition.

PMID- 25375723
TI  - Pseudorotational epitaxy of self-assembled octadecyltrichlorosilane monolayers on
      sapphire (0001).
AB  - The structure of octadecyltrichlorosilane self-assembled monolayers (SAMs) on
      sapphire (0001) was studied by A-resolution surface-specific x-ray scattering
      methods. The monolayer was found to consist of three sublayers where the
      outermost layer corresponds to vertically oriented, closely packed alkyl tails.
      Laterally, the monolayer is hexagonally packed and exhibits pseudorotational
      epitaxy to the sapphire, manifested by a broad scattering peak at zero relative
      azimuthal rotation, with long powderlike tails. The lattice mismatch of ~ 1%-3%
      to the sapphire's and the different length scale introduced by the lateral Si-O
      Si bonding prohibit positional epitaxy. However, the substrate induces an
      intriguing increase in the crystalline coherence length of the SAM's powderlike
      crystallites when rotationally aligned with the sapphire's lattice. The increase
      correlates well with the rotational dependence of the separation of corresponding
      substrate-monolayer lattice sites.

PMID- 25375724
TI  - Structure prediction for multicomponent materials using biminima.
AB  - The potential energy surface of a heteroparticle system will contain points that
      are local minima in both coordinate space and permutation space for the different
      species. We introduce the term biminima to describe these special points, and we
      formulate a deterministic scheme for finding them. Our search algorithm generates
      a converging sequence of particle-identity swaps, each accompanied by a number of
      local geometry relaxations. For selected binary atomic clusters of size N = N(A)
      + N(B) <= 98, convergence to a biminimum on average takes 3 N(A)N(B) relaxations,
      and the number of biminima grows with the preference for mixing. The new
      framework unifies continuous and combinatorial optimization, providing a powerful
      tool for structure prediction and rational design of multicomponent materials.

PMID- 25375725
TI  - Strongly coupled magnons and cavity microwave photons.
AB  - We realize a cavity magnon-microwave photon system in which a magnetic dipole
      interaction mediates strong coupling between the collective motion of a large
      number of spins in a ferrimagnet and the microwave field in a three-dimensional
      cavity. By scaling down the cavity size and increasing the number of spins, an
      ultrastrong coupling regime is achieved with a cooperativity reaching 12,600.
      Interesting dynamic features including classical Rabi-like oscillation,
      magnetically induced transparency, and the Purcell effect are demonstrated in
      this highly versatile platform, highlighting its great potential for coherent
      information processing.

PMID- 25375727
TI  - Spin noise spectroscopy beyond thermal equilibrium and linear response.
AB  - Per the fluctuation-dissipation theorem, the information obtained from spin
      fluctuation studies in thermal equilibrium is necessarily constrained by the
      system's linear response functions. However, by including weak radio frequency
      magnetic fields, we demonstrate that intrinsic and random spin fluctuations even
      in strictly unpolarized ensembles can reveal underlying patterns of correlation
      and coupling beyond linear response, and can be used to study nonequilibrium and
      even multiphoton coherent spin phenomena. We demonstrate this capability in a
      classical vapor of (41)K alkali atoms, where spin fluctuations alone directly
      reveal Rabi splittings, the formation of Mollow triplets and Autler-Townes
      doublets, ac Zeeman shifts, and even nonlinear multiphoton coherences.

PMID- 25375726
TI  - Kitaev chains with long-range pairing.
AB  - We propose and analyze a generalization of the Kitaev chain for fermions with
      long-range p-wave pairing, which decays with distance as a power law with
      exponent alpha. Using the integrability of the model, we demonstrate the
      existence of two types of gapped regimes, where correlation functions decay
      exponentially at short range and algebraically at long range (alpha > 1) or
      purely algebraically (alpha < 1). Most interestingly, along the critical lines,
      long-range pairing is found to break conformal symmetry for sufficiently small
      alpha. This is accompanied by a violation of the area law for the entanglement
      entropy in large parts of the phase diagram in the presence of a gap and can be
      detected via the dynamics of entanglement following a quench. Some of these
      features may be relevant for current experiments with cold atomic ions.

PMID- 25375728
TI  - Valley-polarized interlayer conduction of anisotropic Dirac fermions in SrMnBi2.
AB  - We report the valley-selective interlayer conduction of SrMnBi(2) under in-plane
      magnetic fields. The c-axis resistivity of SrMnBi(2) shows clear angular
      magnetoresistance oscillations indicating coherent interlayer conduction. Strong
      fourfold variation of the coherent peak in the c-axis resistivity reveals that
      the contribution of each Dirac valley is significantly modulated by the in-plane
      field orientation. This originates from anisotropic Dirac Fermi surfaces with
      strong disparity in the momentum-dependent interlayer coupling. Furthermore, we
      found a signature of broken valley symmetry at high magnetic fields. These
      findings demonstrate that a quasi-two-dimensional anisotropic Dirac system can
      host a valley-polarized interlayer current through magnetic valley control.

PMID- 25375729
TI  - Nonlinear valley and spin currents from Fermi pocket anisotropy in 2D crystals.
AB  - The controlled flow of spin and valley pseudospin is key to future electronics
      exploiting these internal degrees of freedom of carriers. Here, we discover a
      universal possibility for generating spin and valley currents by electric bias or
      temperature gradient only, which arises from the anisotropy of Fermi pockets in
      crystalline solids. We find spin and valley currents to the second order in the
      electric field as well as their thermoelectric counterparts, i.e., the nonlinear
      spin and valley Seebeck effects. These second-order nonlinear responses allow two
      unprecedented possibilities to generate pure spin and valley flows without net
      charge current: (i) by an ac bias or (ii) by an arbitrary inhomogeneous
      temperature distribution. As examples, we predict appreciable nonlinear spin and
      valley currents in two-dimensional (2D) crystals including graphene, monolayer
      and trilayer transition-metal dichalcogenides, and monolayer gallium selenide.
      Our finding points to a new route towards electrical and thermal generations of
      spin and valley currents for spintronic and valleytronic applications based on 2D
      quantum materials.

PMID- 25375730
TI  - Direct spectroscopic observation of a shallow hydrogenlike donor state in
      insulating SrTiO3.
AB  - We present a direct spectroscopic observation of a shallow hydrogenlike muonium
      state in SrTiO(3) which confirms the theoretical prediction that interstitial
      hydrogen may act as a shallow donor in this material. The formation of this
      muonium state is temperature dependent and appears below ~ 70K. From the
      temperature dependence we estimate an activation energy of ~ 50 meV in the bulk
      and ~ 23 meV near the free surface. The field and directional dependence of the
      muonium precession frequencies further supports the shallow impurity state with a
      rare example of a fully anisotropic hyperfine tensor. From these measurements we
      determine the strength of the hyperfine interaction and propose that the muon
      occupies an interstitial site near the face of the oxygen octahedron in SrTiO(3).
      The observed shallow donor state provides new insight for tailoring the
      electronic and optical properties of SrTiO(3)-based oxide interface systems.

PMID- 25375732
TI  - Microscopic theory of cation exchange in CdSe nanocrystals.
AB  - Although poorly understood, cation-exchange reactions are increasingly used to
      dope or transform colloidal semiconductor nanocrystals (quantum dots). We use
      density-functional theory and kinetic Monte Carlo simulations to develop a
      microscopic theory that explains structural, optical, and electronic changes
      observed experimentally in Ag-cation-exchanged CdSe nanocrystals. We find that
      Coulomb interactions, both between ionized impurities and with the polarized
      nanocrystal surface, play a key role in cation exchange. Our theory also resolves
      several experimental puzzles related to photoluminescence and electrical behavior
      in CdSe nanocrystals doped with Ag.

PMID- 25375731
TI  - Two-dimensional electron gases at LaAlO3/SrTiO3 interfaces: orbital symmetry and
      hierarchy engineered by crystal orientation.
AB  - Recent findings show the emergence of two-dimensional electron gases (2DEGs) at
      LaAlO(3)/SrTiO(3) interfaces along different orientations; yet details on band
      reconstructions have remained so far unknown. Via x-ray linear dichroism
      spectroscopy, we demonstrate that crystal symmetry imposes distinctive 2DEG
      orbital hierarchies on (001)-and (110)-oriented quantum wells, allowing selective
      occupancy of states of different symmetry. Such orientational tuning expands the
      possibilities for electronic engineering of 2DEGs and opens up enticing
      opportunities to understand the link between orbital symmetry and complex
      correlated states at LaAlO(3)/SrTiO(3) quantum wells.

PMID- 25375733
TI  - MoS 2 MoS2: choice substrate for accessing and tuning the electronic properties
      of graphene.
AB  - One of the enduring challenges in graphene research and applications is the
      extreme sensitivity of its charge carriers to external perturbations, especially
      those introduced by the substrate. The best available substrates to date,
      graphite and hexagonal boron nitride (h-BN), still pose limitations: graphite
      being metallic does not allow gating, while both h-BN and graphite, having
      lattice structures closely matched to that of graphene, may cause significant
      band structure reconstruction. Here we show that the atomically smooth surface of
      exfoliated MoS(2) provides access to the intrinsic electronic structure of
      graphene without these drawbacks. Using scanning tunneling microscopy and Landau
      level (LL) spectroscopy in a device configuration that allows tuning of the
      carrier concentration, we find that graphene on MoS(2) is ultraflat, producing
      long mean free paths, while avoiding band structure reconstruction. Importantly,
      the screening of the MoS(2) substrate can be tuned by changing the position of
      the Fermi energy with relatively low gate voltages. We show that shifting the
      Fermi energy from the gap to the edge of the conduction band gives rise to
      enhanced screening and to a substantial increase in the mean free path and
      quasiparticle lifetime. MoS(2) substrates thus provide unique opportunities to
      access the intrinsic electronic properties of graphene and to study in situ the
      effects of screening on electron-electron interactions and transport.

PMID- 25375701
TI  - Test of lepton universality using b+ -> K+l+l- decays.
AB  - A measurement of the ratio of the branching fractions of the B(+) -> K(+)MU(+)MU(
      ) and B(+) -> K(+)e(+)e(-) decays is presented using proton-proton collision
      data, corresponding to an integrated luminosity of 3.0 fb(-1), recorded with the
      LHCb experiment at center-of-mass energies of 7 and 8 TeV. The value of the ratio
      of branching fractions for the dilepton invariant mass squared range 1 < q(2) < 6
      GeV(2)/c(4) is measured to be 0.745(-0.074)(+0.090)(stat) +/- 0.036(syst). This
      value is the most precise measurement of the ratio of branching fractions to date
      and is compatible with the standard model prediction within 2.6 standard
      deviations.

PMID- 25375734
TI  - Resonant phase matching of Josephson junction traveling wave parametric
      amplifiers.
AB  - We propose a technique to overcome phase mismatch in Josephson-junction traveling
      wave parametric amplifiers in order to achieve high gain over a broad bandwidth.
      Using "resonant phase matching," we design a compact superconducting device
      consisting of a transmission line with subwavelength resonant inclusions that
      simultaneously achieves a gain of 20 dB, an instantaneous bandwidth of 3 GHz, and
      a saturation power of -98 dBm. Such an amplifier is well suited to cryogenic
      broadband microwave measurements such as the multiplexed readout of quantum
      coherent circuits based on superconducting, semiconducting, or nanomechanical
      elements, as well as traditional astronomical detectors.

PMID- 25375736
TI  - Large negative magnetoresistance induced by anionic solid solutions in two
      dimensional spin-frustrated transition metal chalcogenides.
AB  - We report an anionic solid solution process that induces frustrated magnetic
      structures within two-dimensional transition metal chalcogenides, which leads to
      huge negative magnetoresistance effects. Ultrathin nanosheets of TiTe(2-x)I(x)
      solid solutions, which are a new class of inorganic two-dimensional magnetic
      material, exhibit negative magnetoresistance with a value of up to -85%, due to
      the spin-dependent scattering effects of local Ti(3+) 3d(1) moments that are
      antiferromagnetically coupled. Moreover, TiTe(2-x)I(x) serials show unique
      transport behaviors with continuous evolution from metallic to semiconducting
      states. We anticipate that anionic doping will be a powerful tool for optimizing
      the intrinsic physical properties of two-dimensional transition metal
      chalcogenide system.

PMID- 25375737
TI  - Multiferroic rhodium clusters.
AB  - Simultaneous magnetic and electric deflection measurements of rhodium clusters
      (Rh(N), 6 <= N <= 40) reveal ferromagnetism and ferroelectricity at low
      temperatures, while neither property exists in the bulk metal. Temperature
      independent magnetic moments (up to 1 MU(B) per atom) are observed, and
      superparamagnetic blocking temperatures up to 20 K. Ferroelectric dipole moments
      on the order of 1D with transition temperatures up to 30 K are observed.
      Ferromagnetism and ferroelectricity coexist in rhodium clusters in the measured
      size range, with size-dependent variations in the transition temperatures that
      tend to be anticorrelated in the range n = 6-25. Both effects diminish with size
      and essentially vanish at N = 40. The ferroelectric properties suggest a Jahn
      Teller ground state. These experiments represent the first example of
      multiferroic behavior in pure metal clusters.

PMID- 25375735
TI  - Relativistic Neel-order fields induced by electrical current in antiferromagnets.
AB  - We predict that a lateral electrical current in antiferromagnets can induce
      nonequilibrium Neel-order fields, i.e., fields whose sign alternates between the
      spin sublattices, which can trigger ultrafast spin-axis reorientation. Based on
      microscopic transport theory calculations we identify staggered current-induced
      fields analogous to the intraband and to the intrinsic interband spin-orbit
      fields previously reported in ferromagnets with a broken inversion-symmetry
      crystal. To illustrate their rich physics and utility, we consider bulk Mn(2)Au
      with the two spin sublattices forming inversion partners, and a 2D square-lattice
      antiferromagnet with broken structural inversion symmetry modeled by a Rashba
      spin-orbit coupling. We propose an antiferromagnetic memory device with
      electrical writing and reading.

PMID- 25375738
TI  - Phase-sensitive detection of spin pumping via the ac inverse spin Hall effect.
AB  - We use a phase-sensitive, quantitative technique to separate inductive and ac
      inverse spin Hall effect (ISHE) voltages observed in Ni(81)Fe(19)/normal metal
      multilayers under the condition of ferromagnetic resonance. For Ni(81)Fe(19)/Pt
      thin film bilayers and at microwave frequencies from 7 to 20 GHz, we observe an
      ac ISHE magnitude that is much larger than that expected from the dc spin Hall
      angle Theta(SH)(Pt) = 0.1. Furthermore, at these frequencies, we find an
      unexpected, ~ 110 degrees  phase of the ac ISHE signal relative to the in-plane
      component of the resonant magnetization precession. We attribute our findings to
      a dominant intrinsic ac ISHE in Pt.

PMID- 25375739
TI  - Establishing the fundamental magnetic interactions in the chiral Skyrmionic Mott
      insulator Cu(2)OSeO(3) by terahertz electron spin resonance.
AB  - The recent discovery of Skyrmions in Cu(2)OSeO(3) has established a new platform
      to create and manipulate Skyrmionic spin textures. We use high-field electron
      spin resonance with a terahertz free-electron laser and pulsed magnetic fields up
      to 64 T to probe and quantify its microscopic spin-spin interactions. In addition
      to the previously observed long-wavelength Goldstone mode, this technique probes
      also the high-energy part of the excitation spectrum which is inaccessible by
      standard low-frequency electron spin resonance. Fitting the behavior of the
      observed modes in magnetic field to a theoretical framework establishes
      experimentally that the fundamental magnetic building blocks of this Skyrmionic
      magnet are rigid, highly entangled and weakly coupled tetrahedra.

PMID- 25375740
TI  - Distinguishing bulk and surface electron-phonon coupling in the topological
      insulator Bi(2)Se(3) using time-resolved photoemission spectroscopy.
AB  - We report time- and angle-resolved photoemission spectroscopy measurements on the
      topological insulator Bi(2)Se(3). We observe oscillatory modulations of the
      electronic structure of both the bulk and surface states at a frequency of 2.23
      THz due to coherent excitation of an A(1g) phonon mode. A distinct, additional
      frequency of 2.05 THz is observed in the surface state only. The lower phonon
      frequency at the surface is attributed to the termination of the crystal and thus
      reduction of interlayer van der Waals forces, which serve as restorative forces
      for out-of-plane lattice distortions. Density functional theory calculations
      quantitatively reproduce the magnitude of the surface phonon softening. These
      results represent the first band-resolved evidence of the A(1g) phonon mode
      coupling to the surface state in a topological insulator.

PMID- 25375741
TI  - Conditional control of donor nuclear spins in silicon using stark shifts.
AB  - Electric fields can be used to tune donor spins in silicon using the Stark shift,
      whereby the donor electron wave function is displaced by an electric field,
      modifying the hyperfine coupling between the electron spin and the donor nuclear
      spin. We present a technique based on dynamic decoupling of the electron spin to
      accurately determine the Stark shift, and illustrate this using antimony donors
      in isotopically purified silicon-28. We then demonstrate two different methods to
      use a dc electric field combined with an applied resonant radio-frequency (rf)
      field to conditionally control donor nuclear spins. The first method combines an
      electric-field induced conditional phase gate with standard rf pulses, and the
      second one simply detunes the spins off resonance. Finally, we consider different
      strategies to reduce the effect of electric field inhomogeneities and obtain
      above 90% process fidelities. 

PMID- 25375742
TI  - Consequences of oxygen-vacancy correlations at the SrTiO3 interface.
AB  - The Kondo effect and ferromagnetism are the two many-body phenomena that emerge
      at the SrTiO(3) interfaces with polar materials, but do not occur in bulk
      SrTiO(3). By regarding the oxygen vacancy (OV) in SrTiO(3) as a magnetic
      impurity, we show that these two interface-specific phenomena can be attributed
      to the vacancies residing in the top TiO(2) plane of SrTiO(3). We identify three
      crucial ingredients: the local orbital mixing caused by an OV, reduced symmetry
      at the interface, and a strong in-plane stray electric field of the polar
      material. All three factors combine to result in the coupling between the
      impurity and conduction band at the interface, and can lead to both emergent
      phenomena. An OV-based Anderson impurity model is derived and solved using the
      numerical renormalization group method. The Kondo and Curie temperatures are
      estimated. Several experiments are discussed based on this interpretation.

PMID- 25375743
TI  - Optical measurement of the effect of electric fields on the nuclear spin
      coherence of rare-earth ions in solids.
AB  - We show that the coherence properties of the nuclear spin states of rare-earth
      ions in solids can be manipulated by small applied electric fields. This was done
      by measuring the Stark effect on the nuclear quadrupole transitions of (151)Eu in
      Y(2)SiO(5) (YSO) using a combination of Raman heterodyne optical detection and
      Stark modulated quadrupole echoes to achieve high sensitivity. The measured Stark
      coefficients were 0.42 and 1.0 Hz cm/V for the two quadrupole transitions at
      34.54 and 46.20 MHz, respectively. The long decoherence time of the nuclear spin
      states (25 ms) allowed us to make the measurements in very low electric fields of
      ~ 10 V/cm, which produced 100% modulation of the nuclear spin echo, and to
      measure Stark shifts of ~ 1 Hz or 20 ppm of the inhomogeneous linewidth.

PMID- 25375744
TI  - Correlation of local order with particle mobility in supercooled liquids is
      highly system dependent.
AB  - We investigate the connection between local structure and dynamical heterogeneity
      in supercooled liquids. Through the study of four different models, we show that
      the correlation between a particle's mobility and the degree of local order in
      nearby regions is highly system dependent. Our results suggest that the
      correlation between local structure and dynamics is weak or absent in systems
      that conform well to the mean-field picture of glassy dynamics and strong in
      those that deviate from this paradigm. Finally, we investigate the role of order
      agnostic point-to-set correlations and reveal that they provide similar
      information content to local structure measures, at least in the system where
      local order is most pronounced. 

PMID- 25375705
TI  - First observation of a baryonic Bc+ decay.
AB  - A baryonic decay of the B(c)(+) meson, B(c)(+) -> J/psipppi(+), is observed for
      the first time, with a significance of 7.3 standard deviations, in pp collision
      data collected with the LHCb detector and corresponding to an integrated
      luminosity of 3.0 fb(-1) taken at center-of-mass energies of 7 and 8 TeV. With
      the B(c)(+) -> J/psipi(+) decay as the normalization channel, the ratio of
      branching fractions is measured to be B(B(c)(+) -> J/psipppi(+))/B(B(c)(+) ->
      J/psipi(+)) = 0.143(-0.034)(+0.039)(stat) +/- 0.013(syst). The mass of the
      B(c)(+) meson is determined as M(B(c)(+) = 6274.0 +/- 1.8(stat) +/- 0.4(syst)
      MeV/c(2), using the B(c)(+) -> J/psipppi(+) channel.

PMID- 25375745
TI  - Spatial symmetry breaking determines spiral wave chirality.
AB  - Chirality represents a fundamental property of spiral waves. Introducing
      obstacles into cardiac monolayers leads to the initiation of clockwise-rotating,
      counterclockwise-rotating, and pairs of spiral waves. Simulations show that the
      precise location of the obstacle and the pacing frequency determine spiral wave
      chirality. Instabilities predicted by curves relating the action potential
      duration and the pacing frequency at different spatial locations predict sites of
      wave break initiation and, hence, spiral wave chirality. 

PMID- 25375746
TI  - Penrose tilings as jammed solids.
AB  - Penrose tilings form lattices, exhibiting fivefold symmetry and isotropic
      elasticity, with inhomogeneous coordination much like that of the force networks
      in jammed systems. Under periodic boundary conditions, their average coordination
      is exactly four. We study the elastic and vibrational properties of rational
      approximants to these lattices as a function of unit-cell size N(S) and find that
      they have of order sqrt[N(S)] zero modes and states of self-stress and yet all
      their elastic moduli vanish. In their generic form, obtained by randomizing site
      positions, their elastic and vibrational properties are similar to those of
      particulate systems at jamming with a nonzero bulk modulus, vanishing shear
      modulus, and a flat density of states.

PMID- 25375747
TI  - Manipulating semiconductor colloidal stability through doping.
AB  - The interface between a doped semiconductor material and electrolyte solution is
      of considerable fundamental interest, and is relevant to systems of practical
      importance. Both adjacent domains contain mobile charges, which respond to
      potential variations. This is exploited to design electronic and optoelectronic
      sensors, and other enabling semiconductor colloidal materials. We show that the
      charge mobility in both phases leads to a new type of interaction between
      semiconductor colloids suspended in aqueous electrolyte solutions. This
      interaction is due to the electrostatic response of the semiconductor interior to
      disturbances in the external field upon the approach of two particles. The
      electrostatic repulsion between two charged colloids is reduced from the one
      governed by the charged groups present at the particles surfaces. This type of
      interaction is unique to semiconductor particles and may have a substantial
      effect on the suspension dynamics and stability. 

PMID- 25375748
TI  - Comment on "Single-slit electron diffraction with Aharonov-Bohm phase: Feynman's
      thought experiment with quantum point contacts".

PMID- 25375749
TI  - Khatua, Bansal, and Shahar reply.

PMID- 25375750
TI  - Comparison of Magnetic Intensities for Mesenchymal Stem Cell Targeting Therapy on
      Ischemic Myocardial Repair: High Magnetic Intensity Improves Cell Retention but
      Has no Additional Functional Benefit.
AB  - Magnetic targeting has the potential to enhance the therapeutic effects of stem
      cells through increasing retention of transplanted cells. To investigate the
      effects of magnetic targeting intensities on cell transplantation, we performed
      different magnetic intensities for mesenchymal stem cell (MSC)-targeting therapy
      in a rat model of ischemia/reperfusion. Rat MSCs labeled with superparamagnetic
      oxide nanoparticles (SPIOs) were injected into the left ventricular (LV) cavity
      of rats during a brief aorta and pulmonary artery occlusion. The 0.15 Tesla (T),
      0.3 T, and 0.6 T magnets were placed 0~1 mm above the injured myocardium during
      and after the injection of 1 * 10(6) MSCs. Fluorescence imaging and quantitative
      PCR revealed that magnetic targeting enhanced cell retention in the heart at 24 h
      in a magnetic field strength-dependent manner. Compared with the 0 T group, three
      magnetic targeting groups enhanced varying cell engraftment at 3 weeks, at which
      time LV remodeling was maximally attenuated, and the therapeutic benefit (LV
      ejection fraction) was also highest in the 0.3 T groups. Interestingly, due to
      the low MSC engraftment resulting from microvascular embolisms, the 0.6 T group
      failed to translate into additional therapeutic outcomes, though it had the
      highest cell retention. Magnetic targeting enhances cell retention in a magnetic
      field strength-dependent manner. However, too high of a magnetic intensity may
      result in microembolization and consequently undermine the functional benefits of
      cell transplantation. 

PMID- 25375751
TI  - CT findings of the main pathological conditions associated with horseshoe
      kidneys.
AB  - Horseshoe kidney (HSK) is the most common renal fusion anomaly, with a prevalence
      of 0.25% among the general population. It consists of kidney fusion across the
      midline. HSK can be present as an isolated condition in 30%, but there is a wide
      variety of associated abnormalities. The most frequent include ureteropelvic
      obstruction, lithiasis and infections. There is also a higher risk of kidney
      lesions in trauma and an increased incidence of malignancies. Awareness of
      embryology and anatomy is essential to assess and understand the complications
      affecting HSK. CT is an excellent method for identification of its main findings.

PMID- 25375752
TI  - The protonated and sodiated dimers of proline studied by IRMPD spectroscopy in
      the N-H and O-H stretching region and computational methods.
AB  - IRMPD spectroscopy and computational chemistry techniques have been used to
      determine that the proton- and sodium-bound dimers of proline exist as a mixture
      of a number of different structures. Simulated annealing computations were found
      to be helpful in determining the unique structures of the protonated and sodiated
      dimers, augmenting chemical intuition. The experimental and computational results
      are consistent with the proton-bound dimer of N-protonated proline bound to
      zwitterionic proline. There was no spectroscopic evidence in the 3200-3800 cm(-1)
      region for a canonical structure which is predicted to have a weak N-H stretch at
      about 3440 cm(-1). A well resolved band at 1733 cm(-1) from a previous
      spectroscopic study (DOI: 10.1021/ja068715a ) was reassigned from a high energy
      canonical isomer to the C=O stretch of a lower energy zwitterionic structure.
      This band is a free carboxylate C=O stretch where protonated proline is hydrogen
      bonded to the other carboxylate oxygen which is also involved in an
      intramolecular hydrogen bond. Fifteen structures of the sodium bound proline
      dimer were computed to be within 10 kJ mol(-1) of Gibbs energy and eight
      structures were within 5 kJ mol(-1). None of these structures can be ruled out
      based on the experimental IRMPD spectrum. They all have an N-H stretching band
      predicted in a position that agrees with the experimental spectrum. However, only
      structures where one of the proline monomers is in the canonical form and having
      a free O-H bond can produce the band at ~3600 cm(-1).

PMID- 25375753
TI  - Design of a lossless image compression system for video capsule endoscopy and its
      performance in in-vivo trials.
AB  - In this paper, a new low complexity and lossless image compression system for
      capsule endoscopy (CE) is presented. The compressor consists of a low-cost YEF
      color space converter and variable-length predictive with a combination of Golomb
      Rice and unary encoding. All these components have been heavily optimized for low
      power and low-cost and lossless in nature. As a result, the entire compression
      system does not incur any loss of image information. Unlike transform based
      algorithms, the compressor can be interfaced with commercial image sensors which
      send pixel data in raster-scan fashion that eliminates the need of having large
      buffer memory. The compression algorithm is capable to work with white light
      imaging (WLI) and narrow band imaging (NBI) with average compression ratio of 78%
      and 84% respectively. Finally, a complete capsule endoscopy system is developed
      on a single, low-power, 65-nm field programmable gate arrays (FPGA) chip. The
      prototype is developed using circular PCBs having a diameter of 16 mm. Several in
      vivo and ex-vivo trials using pig's intestine have been conducted using the
      prototype to validate the performance of the proposed lossless compression
      algorithm. The results show that, compared with all other existing works, the
      proposed algorithm offers a solution to wireless capsule endoscopy with lossless
      and yet acceptable level of compression. 

PMID- 25375754
TI  - Human mobility monitoring in very low resolution visual sensor network.
AB  - This paper proposes an automated system for monitoring mobility patterns using a
      network of very low resolution visual sensors (30 * 30 pixels). The use of very
      low resolution sensors reduces privacy concern, cost, computation requirement and
      power consumption. The core of our proposed system is a robust people tracker
      that uses low resolution videos provided by the visual sensor network. The
      distributed processing architecture of our tracking system allows all image
      processing tasks to be done on the digital signal controller in each visual
      sensor. In this paper, we experimentally show that reliable tracking of people is
      possible using very low resolution imagery. We also compare the performance of
      our tracker against a state-of-the-art tracking method and show that our method
      outperforms. Moreover, the mobility statistics of tracks such as total distance
      traveled and average speed derived from trajectories are compared with those
      derived from ground truth given by Ultra-Wide Band sensors. The results of this
      comparison show that the trajectories from our system are accurate enough to
      obtain useful mobility statistics. 

PMID- 25375756
TI  - Using smart phone sensors to detect transportation modes.
AB  - The proliferation of mobile smart devices has led to a rapid increase of location
      based services, many of which are amassing large datasets of user trajectory
      information. Unfortunately, current trajectory information is not yet
      sufficiently rich to support classification of user transportation modes. In this
      paper, we propose a method that employs both the Global Positioning System and
      accelerometer data from smart devices to classify user outdoor transportation
      modes. The classified modes include walking, bicycling, and motorized transport,
      in addition to the motionless (stationary) state, for which we provide new depth
      analysis. In our classification, stationary mode has two sub-modes: stay
      (remaining in the same place for a prolonged time period; e.g., in a parked
      vehicle) and wait (remaining at a location for a short period; e.g., waiting at a
      red traffic light). These two sub-modes present different semantics for data
      mining applications. We use support vector machines with parameters that are
      optimized for pattern recognition. In addition, we employ ant colony optimization
      to reduce the dimension of features and analyze their relative importance. The
      resulting classification system achieves an accuracy rate of 96.31% when applied
      to a dataset obtained from 18 mobile users. 

PMID- 25375755
TI  - Dual-frequency piezoelectric transducers for contrast enhanced ultrasound
      imaging.
AB  - For many years, ultrasound has provided clinicians with an affordable and
      effective imaging tool for applications ranging from cardiology to obstetrics.
      Development of microbubble contrast agents over the past several decades has
      enabled ultrasound to distinguish between blood flow and surrounding tissue.
      Current clinical practices using microbubble contrast agents rely heavily on user
      training to evaluate degree of localized perfusion. Advances in separating the
      signals produced from contrast agents versus surrounding tissue backscatter
      provide unique opportunities for specialized sensors designed to image
      microbubbles with higher signal to noise and resolution than previously possible.
      In this review article, we describe the background principles and recent
      developments of ultrasound transducer technology for receiving signals produced
      by contrast agents while rejecting signals arising from soft tissue. This
      approach relies on transmitting at a low-frequency and receiving microbubble
      harmonic signals at frequencies many times higher than the transmitted frequency.
      Design and fabrication of dual-frequency transducers and the extension of recent
      developments in transducer technology for dual-frequency harmonic imaging are
      discussed. 

PMID- 25375757
TI  - Accuracy assessment of the integration of GNSS and a MEMS IMU in a terrestrial
      platform.
AB  - MEMS Inertial Measurement Units are available at low cost and can replace
      expensive units in mobile mapping platforms which need direct georeferencing.
      This is done through the integration with GNSS measurements in order to achieve a
      continuous positioning solution and to obtain orientation angles. This paper
      presents the results of the assessment of the accuracy of a system that
      integrates GNSS and a MEMS IMU in a terrestrial platform. We describe the
      methodology used and the tests realized where the accuracy of the positions and
      orientation parameters were assessed using an independent photogrammetric
      technique employing cameras that integrate the mobile mapping system developed by
      the authors. Results for the accuracy of attitude angles and coordinates show
      that accuracies better than a decimeter in positions, and under a degree in
      angles, can be achieved even considering that the terrestrial platform is
      operating in less than favorable environments. 

PMID- 25375758
TI  - Sensor fusion of cameras and a laser for city-scale 3D reconstruction.
AB  - This paper presents a sensor fusion system of cameras and a 2D laser sensorfor
      large-scale 3D reconstruction. The proposed system is designed to capture data on
      afast-moving ground vehicle. The system consists of six cameras and one 2D laser
      sensor,and they are synchronized by a hardware trigger. Reconstruction of 3D
      structures is doneby estimating frame-by-frame motion and accumulating vertical
      laser scans, as in previousworks. However, our approach does not assume near 2D
      motion, but estimates free motion(including absolute scale) in 3D space using
      both laser data and image features. In orderto avoid the degeneration associated
      with typical three-point algorithms, we present a newalgorithm that selects 3D
      points from two frames captured by multiple cameras. The problemof error
      accumulation is solved by loop closing, not by GPS. The experimental resultsshow
      that the estimated path is successfully overlaid on the satellite images, such
      that thereconstruction result is very accurate. 

PMID- 25375759
TI  - Response to: "Oh, no--equations! Reanalysis of the data reveal even stronger
      associations between Hashimoto's thyroiditis and differentiated thyroid cancer".

PMID- 25375760
TI  - High-mobility solution-processed tin oxide thin-film transistors with high-kappa
      alumina dielectric working in enhancement mode.
AB  - Solution-processed metal oxide thin-film transistors (TFTs) operating in
      enhancement mode are promising for the next-generation flat panel displays. In
      this work, we report high-mobility TFTs based on SnO2 active layer derived from a
      soluble tin(II) 2-ethylhexanoate precursor. Densely packed polycrystalline SnO2
      thin films with moderate oxygen vacancies and only a few hydroxides are obtained
      via systemically optimizing precursor concentrations and processing conditions.
      The utilization of a solution-processed high-kappa Al2O3 insulating layer could
      generate a coherent dielectric/semiconductor interface, hence further improving
      the device performance. TFT devices with an average field-effect mobility of 96.4
      cm(2) V(-1) s(-1), a current on/off ratio of 2.2 * 10(6), a threshold voltage of
      1.72 V, and a subthreshold swing of 0.26 V dec(-1) have been achieved, and the
      driving capability is demonstrated by implementing a single SnO2 TFT device to
      tune the brightness of an organic light-emitting diode. It is worth noting that
      these TFTs work in enhancement mode at low voltages less than 4 V, which sheds
      light on their potential application to the next-generation low-cost active
      matrix flat panel displays. 

PMID- 25375762
TI  - Cell-penetrating poly(disulfide)s: the dependence of activity, depolymerization
      kinetics and intracellular localization on their length.
AB  - We report that the depolymerization kinetics of cell-penetrating poly(disulfide)s
      depend exclusively on their length and propose a kinetic uptake model to explain
      why their intracellular destination changes with the increasing length from the
      endosomes over the cytosol to the nucleoli. 

PMID- 25375761
TI  - Toxic oligomer species of amyloid-beta in Alzheimer's disease, a timing issue.
AB  - A decade following the paradigm-shifting concept that endogenous forms of
      soluble, non-fibrillar amyloid-beta (Abeta) might constitute the major bioactive
      entity causing synaptic loss and cognitive decline in Alzheimer's disease (AD),
      our understanding of these oligomeric species still remains conspicuously
      superficial. The current lack of direct evaluation tools for each endogenous
      Abeta oligomer hampers our ability to readily address crucial question such as:
      (i) where they form and accumulate?; (ii) when they first appear in human brains
      and body fluids?; (iii) what is the longitudinal expression of these putative
      toxins during the course of the disease?; (iv) and how do these soluble Abeta
      assemblies alter synaptic and neuronal function in the brain? Despite these
      limitations, indirect ex vivo measurement and isolation from biological specimens
      has been possible and have allowed parsing out intrinsic differences between
      putative endogenous Abeta oligomers. In this review, I integrated recent findings
      and extrapolated emerging hypotheses derived from these studies with the hope to
      provide a clarified view on the putative role of endogenous Abeta oligomers in
      AD, with a particular emphasis on the timing at which these soluble species might
      act in the aging and diseased brain. 

PMID- 25375763
TI  - The Etiology of Epiphora: A Multifactorial Issue.
AB  - OBJECTIVES: Epiphora (excess tearing) is a common complaint among patients
      visiting ophthalmology clinics. The etiology of epiphora in patients presenting
      to a primary ophthalmologist might be very different compared to those referred
      to an oculoplastic unit. PURPOSE: To describe the etiology of epiphora in
      patients referred to an oculoplastics clinic. METHODS: A retrospective,
      observational study of all consecutive referrals to oculoplastic service for
      epiphora in 2011-2012. Slit-lamp examination, eyelid position, dry eye tests,
      ocular surface pathology, the patency of the nasolacrimal system, and punctal
      aperture were evaluated. RESULTS: A total of 445 eyes of 280 patients (205 men;
      46.1%) participated. The mean age was 69.4 +/- 15 (range 15-96) years. Bilateral
      epiphora occurred in 165 (58.9%) patients and unilateral in 115 (41.1%). The
      etiologies referred for epiphora were lower lid malposition (33.3%),
      nasolacrimal/canalicular obstruction (29%), multifactorial (22%), punctal
      stenosis (11%), and reflex tearing (4.7%). Women were younger than men (p <
      0.0001). More women had punctal stenosis compared to men (34.6% versus 22.4%, p =
      0.01), and more men had eyelid malposition than women (39.5% versus 27.9%, p =
      0.005). CONCLUSIONS: Women with epiphora tend to present with nasolacrimal duct
      obstruction and punctal stenosis at younger ages, and unilaterally more often
      than men. Men with epiphora were older, with more cases attributed to laxity of
      the lower eyelid. Multiple etiologies frequently need to be addressed to achieve
      optimal results in treating epiphora.

PMID- 25375765
TI  - Histidine-derived nontoxic nitrogen-doped carbon dots for sensing and bioimaging
      applications.
AB  - Nitrogen-doped (N-doped) photoluminescent carbon dots (CDs) were prepared by a
      one-pot microwave-assisted hydrothermal treatment using histidine as the sole
      carbon source in the absence of acid, alkali, or metal ions. With a diameter of 2
      5 nm, the synthesized CDs had apparent lattice fringes and exhibited an
      excitation-dependent photoluminescent behavior. The CDs were highly yielded, well
      dispersed in aqueous solution, and showed high photostability in the solutions of
      a wide range of pH and salinity. They were used as probes to identify the
      presence of Fe(3+) ions with a detection limit of 10 nM. With confirmed
      nontoxicity, these CDs could enter the cancer cells, indicating a practical
      potential for cellular imaging and labeling. 

PMID- 25375764
TI  - RNA-seq analysis and de novo transcriptome assembly of Jerusalem artichoke
      (Helianthus tuberosus Linne).
AB  - Jerusalem artichoke (Helianthus tuberosus L.) has long been cultivated as a
      vegetable and as a source of fructans (inulin) for pharmaceutical applications in
      diabetes and obesity prevention. However, transcriptomic and genomic data for
      Jerusalem artichoke remain scarce. In this study, Illumina RNA sequencing (RNA
      Seq) was performed on samples from Jerusalem artichoke leaves, roots, stems and
      two different tuber tissues (early and late tuber development). Data were used
      for de novo assembly and characterization of the transcriptome. In total
      206,215,632 paired-end reads were generated. These were assembled into 66,322
      loci with 272,548 transcripts. Loci were annotated by querying against the NCBI
      non-redundant, Phytozome and UniProt databases, and 40,215 loci were homologous
      to existing database sequences. Gene Ontology terms were assigned to 19,848 loci,
      15,434 loci were matched to 25 Clusters of Eukaryotic Orthologous Groups
      classifications, and 11,844 loci were classified into 142 Kyoto Encyclopedia of
      Genes and Genomes pathways. The assembled loci also contained 10,778 potential
      simple sequence repeats. The newly assembled transcriptome was used to identify
      loci with tissue-specific differential expression patterns. In total, 670 loci
      exhibited tissue-specific expression, and a subset of these were confirmed using
      RT-PCR and qRT-PCR. Gene expression related to inulin biosynthesis in tuber
      tissue was also investigated. Exsiting genetic and genomic data for H. tuberosus
      are scarce. The sequence resources developed in this study will enable the
      analysis of thousands of transcripts and will thus accelerate marker-assisted
      breeding studies and studies of inulin biosynthesis in Jerusalem artichoke. 

PMID- 25375766
TI  - Epidemiological trends of dengue disease in Thailand (2000-2011): a systematic
      literature review.
AB  - A literature survey and analysis was conducted to describe the epidemiology of
      dengue disease in Thailand reported between 2000 and 2011. The literature search
      identified 610 relevant sources, 40 of which fulfilled the inclusion criteria
      defined in the review protocol. Peaks in the number of cases occurred during the
      review period in 2001, 2002, 2008 and 2010. A shift in age group predominance
      towards older ages continued through the review period. Disease incidence and
      deaths remained highest in children aged <= 15 years and case fatality rates were
      highest in young children. Heterogeneous geographical patterns were observed with
      higher incidence rates reported in the Southern region and serotype distribution
      varied in time and place. Gaps identified in epidemiological knowledge regarding
      dengue disease in Thailand provide several avenues for future research, in
      particular studies of seroprevalence. PROTOCOL REGISTRATION: PROSPERO
      CRD42012002170.

PMID- 25375767
TI  - Challenges and opportunities: what can we learn from patients living with chronic
      musculoskeletal conditions, health professionals and carers about the concept of
      health literacy using qualitative methods of inquiry?
AB  - The field of health literacy continues to evolve and concern public health
      researchers and yet remains a largely overlooked concept elsewhere in the
      healthcare system. We conducted focus group discussions in England UK, about the
      concept of health literacy with older patients with chronic musculoskeletal
      conditions (mean age  = 73.4 years), carers and health professionals. Our
      research posed methodological, intellectual and practical challenges. Gaps in
      conceptualisation and expectations were revealed, reiterating deficiencies in
      predominant models for understanding health literacy and methodological
      shortcomings of using focus groups in qualitative research for this topic.
      Building on this unique insight into what the concept of health literacy meant to
      participants, we present analysis of our findings on factors perceived to foster
      and inhibit health literacy and on the issue of responsibility in health
      literacy. Patients saw health literacy as a result of an inconsistent interactive
      process and the implications as wide ranging; healthcare professionals had more
      heterogeneous views. All focus group discussants agreed that health literacy most
      benefited from good inter-personal communication and partnership. By proposing a
      needs-based approach to health literacy we offer an alternative way of
      conceptualising health literacy to help improve the health of older people with
      chronic conditions. 

PMID- 25375770
TI  - Description of Caenorhabditis sinica sp. n. (Nematoda: Rhabditidae), a nematode
      species used in comparative biology for C. elegans.
AB  - We re-isolated in China a relative of the nematode model Caenorhabditis elegans
      that was previously referred to informally as C. sp. 5. In spite of its
      importance for comparative biology, C. sp. 5 has remained morphologically
      uncharacterized. Therefore, we now provide detailed description of morphology and
      anatomy, assigning the name of Caenorhabditis sinica sp. n. to this nematode that
      is found frequently in China. C. sinica sp. n. belongs to the Elegans group in
      the genus Caenorhabditis, being phylogenetically close to C. briggsae although
      differing in reproductive mode. The gonochoristic C. sinica sp. n. displays two
      significantly larger distal parts of uteri filled with sperms in the
      female/hermaphroditic gonad than does the androdioecious C. briggsae. The new
      species can be differentiated morphologically from all known Caenorhabditis
      species within the Elegans group by presenting a uniquely shaped, three-pointed
      hook structure on the male precloacal lip. The lateral field of C. sinica sp. n.
      is marked by three ridges that are flanked by two additional incisures, sometimes
      appearing as five ridges in total. This study ends the prolonged period of the
      'undescribed' anonymity for C. sinica sp. n. since its discovery and use in
      comparative biological research. Significant and crossing-direction dependent
      hybrid incompatibilities in F1 and F2 crossing progeny make C. sinica sp. n. an
      excellent model for studies of population and speciation genetics. The abundance
      of nematode species lacking detailed taxonomic characterization deserves renewed
      attention to address the species description gap for this important yet
      morphologically 'difficult' group of animals. 

PMID- 25375771
TI  - Synthesis of a novel cyclic prodrug of S-allyl-glutathione able to attenuate LPS
      induced ROS production through the inhibition of MAPK pathways in U937 cells.
AB  - A novel cyclic prodrug of S-allyl-glutathione (CP11), obtained by using an
      acyloxy-alkoxy linker, was estimated for its pharmacokinetic and biological
      properties. The stability of CP11 was evaluated at pH 1.2, 7.4, in simulated
      fluids with different concentrations of enzymes, and in human plasma. The anti
      inflammatory ability of CP11 was assessed in U937 cells, an immortalized human
      monocyte cell line. Results showed that CP11 is stable at acidic pH showing a
      possible advantage for oral delivery due to the longer permanence in the stomach.
      Having a permeability coefficient of 2.49 * 10(-6) cm s(-1), it was classified as
      discrete BBB-permeable compound. Biological studies revealed that CP11 is able to
      modulate inflammation mediated by LPS in U937 cells preventing the increase of
      ROS intracellular levels through interaction with the MAPK pathway. 

PMID- 25375772
TI  - Total synthesis of (+/-)-antroquinonol d.
AB  - Total synthesis of (+/-)-antroquinonol D, which is isolated from very expensive
      and rarely found Antrodia camphorata and which has potential anticancer
      properties, was achieved from 4-methoxyphenol. In addition, a Michael addition to
      dimethoxy cyclohexadienones was studied. The main step involved chelation and
      substrate-controlled diastereoselective reduction of cyclohexenone and
      lactonization. Lactone synthesis facilitated the diastereoselective reduction of
      ketone, which help control the desired stereochemistry at the crucial stereogenic
      center in the natural product. Other key reactions in the synthesis involved a
      Michael addition of dimethyl malonate on cyclohexadienone, dihydroxylation, and
      Wittig olefination. A sesquiterpene side chain was synthesized through coupling
      with geranyl phenyl sulfide and Bouveault-Blanc reduction. 

PMID- 25375769
TI  - Light-driven Na(+) pump from Gillisia limnaea: a high-affinity Na(+) binding site
      is formed transiently in the photocycle.
AB  - A group of microbial retinal proteins most closely related to the proton pump
      xanthorhodopsin has a novel sequence motif and a novel function. Instead of, or
      in addition to, proton transport, they perform light-driven sodium ion transport,
      as reported for one representative of this group (KR2) from Krokinobacter. In
      this paper, we examine a similar protein, GLR from Gillisia limnaea, expressed in
      Escherichia coli, which shares some properties with KR2 but transports only
      Na(+). The absorption spectrum of GLR is insensitive to Na(+) at concentrations
      of <=3 M. However, very low concentrations of Na(+) cause profound differences in
      the decay and rise time of photocycle intermediates, consistent with a switch
      from a "Na(+)-independent" to a "Na(+)-dependent" photocycle (or photocycle
      branch) at ~60 MUM Na(+). The rates of photocycle steps in the latter, but not
      the former, are linearly dependent on Na(+) concentration. This suggests that a
      high-affinity Na(+) binding site is created transiently after photoexcitation,
      and entry of Na(+) from the bulk to this site redirects the course of events in
      the remainder of the cycle. A greater concentration of Na(+) is needed for
      switching the reaction path at lower pH. The data suggest therefore competition
      between H(+) and Na(+) to determine the two alternative pathways. The idea that a
      Na(+) binding site can be created at the Schiff base counterion is supported by
      the finding that upon perturbation of this region in the D251E mutant, Na(+)
      binds without photoexcitation. Binding of Na(+) to the mutant shifts the
      chromophore maximum to the red like that of H(+), which occurs in the photocycle
      of the wild type. 

PMID- 25375774
TI  - Ammonium recognition by 18-crown-6 in different solutions and at an aqueous
      interface: a simulation study.
AB  - The complexation of alkylammonium RNH3(+) cations by 18-crown-6 (18C6) is studied
      by molecular dynamics (MD) and potential of mean force (PMF) simulations in
      different solvents (methanol, chloroform, 90:10 chloroform/methanol mixture,
      water) and at the chloroform/water interface. The free energies of association
      DeltaGass, obtained with different charge models of 18C6, are compared for
      PrNH3(+) and K(+) cations yielding, with suitable electrostatic models, a
      preference for K(+) in the different monophasic solutions, as well as in the gas
      phase. Furthermore, for a given cation, DeltaGass is markedly solvent dependent
      and decreases in magnitude in the order chloroform ? mixture > methanol > water,
      that is, with the (de)solvation energy of the cation and with the extent of
      pairing with the counterion (here, picrate, Pic(-)). Despite their macroscopic
      intermiscibilities at all proportions, chloroform and methanol are found to form,
      at the microscopic level, an inhomogeneous liquid that displays dual solvation
      properties toward its solutes. As a result, in the monophasic 90:10 mixture that
      contains mainly chloroform, the DeltaGass energies for PrNH3(+) or K(+)
      complexation are closer to those in methanol than to those in chloroform. On the
      other hand, chloroform and water form a biphasic mixture and delineate an
      interface onto which 18C6 and the tBuNH3(+) and Pic(-) ions, as well as their
      complex, are found to adsorb, a feature also supported by the different free
      energy profiles for interface crossing. Interestingly, the complexation energy of
      tBuNH3(+) is found to be stronger at the interface than in pure water,
      demonstrating the crucial role of complexation by 18C6 at the interface to
      promote the cation transfer to the organic phase. 

PMID- 25375773
TI  - Kinetic studies on the reaction between dicyanocobinamide and hypochlorous acid.
AB  - Hypochlorous acid (HOCl) is a potent oxidant generated by myeloperoxidase (MPO),
      which is an abundant enzyme used for defense against microbes. We examined the
      potential role of HOCl in corrin ring destruction and subsequent formation of
      cyanogen chloride (CNCl) from dicyanocobinamide ((CN)2-Cbi). Stopped-flow
      analysis revealed that the reaction consists of at least three observable steps,
      including at least two sequential transient intermediates prior to corrin ring
      destruction. The first two steps were attributed to sequential replacement of the
      two cyanide ligands with hypochlorite, while the third step was the destruction
      of the corrin ring. The formation of (OCl)(CN)-Cbi and its conversion to (OCl)2
      Cbi was fitted to a first order rate equation with second order rate constants of
      0.002 and 0.0002 uM(-1) s(-1), respectively. The significantly lower rate of the
      second step compared to the first suggests that the replacement of the first
      cyanide molecule by hypochlorite causes an alteration in the ligand trans effects
      changing the affinity and/or accessibility of Co toward hypochlorite. Plots of
      the apparent rate constants as a function of HOCl concentration for all the three
      steps were linear with Y-intercepts close to zero, indicating that HOCl binds in
      an irreversible one-step mechanism. Collectively, these results illustrate
      functional differences in the corrin ring environments toward binding of diatomic
      ligands.

PMID- 25375775
TI  - Impact of appropriate antimicrobial therapy for patients with severe sepsis and
      septic shock--a quality improvement study.
AB  - BACKGROUND: There is ample literature available on the association between both
      time to antibiotics and appropriateness of antibiotics and clinical outcomes from
      sepsis. In fact, the current state of debate surrounds the balance to be struck
      between prompt empirical therapy and care in the choice of appropriate
      antibiotics (both in terms of the susceptibility of infecting organism and
      minimizing resistance arising from use of broad-spectrum agents). The objective
      of this study is to determine sepsis bundle compliance and the appropriateness of
      antimicrobial therapy in patients with severe sepsis and septic shock and its
      impact on outcomes. MATERIAL: This study was conducted in the ICU of a tertiary
      care, private hospital in Sao Paulo, Brazil. A retrospective cohort study was
      conducted from July 2005 to December 2012 in patients with severe sepsis and
      septic shock. RESULTS: A total of 1,279 patients were identified with severe
      sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI).
      The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over
      time there was a progressive increase in serum arterial lactate collection,
      obtaining blood cultures prior to antibiotic administration, administration of
      broad-spectrum antibiotics within 1 hour, and administration of appropriate
      antimicrobials, with statistically significant differences in the later years of
      the study. We also observed a significant decrease in mortality. In patients with
      bloodstream infection, after adjustment for other covariates the administration
      of appropriate antimicrobial therapy was associated with a decrease in mortality
      in patients with severe sepsis and septic shock (p = 0.023). CONCLUSIONS: The
      administration of appropriate antimicrobial therapy was independently associated
      with a decline in mortality in patients with severe sepsis and septic shock due
      to bloodstream infection. As protocol adherence increased over time, the crude
      mortality rate decreased, which reinforces the need to implement institutional
      guidelines and monitor appropriate antimicrobial therapy compliance.

PMID- 25375776
TI  - The value of patch-choice copying in fruit flies.
AB  - Many animals copy the choices of others but the functional and mechanistic
      explanations for copying are still not fully resolved. We relied on novel
      behavioral protocols to quantify the value of patch-choice copying in fruit
      flies. In a titration experiment, we quantified how much nutritional value
      females were willing to trade for laying eggs on patches already occupied by
      larvae (social patches). Females were highly sensitive to nutritional quality,
      which was positively associated with their offspring success. Females, however,
      perceived social, low-nutrition patches (33% of the nutrients) as equally
      valuable as non-social, high-nutrition ones (100% of the nutrients). In follow-up
      experiments, we could not, however, either find informational benefits from
      copying others or detect what females' offspring may gain from developing with
      older larvae. Because patch-choice copying in fruit flies is a robust phenomenon
      in spite of potential costs due to competition, we suggest that it is beneficial
      in natural settings, where fruit flies encounter complex dynamics of microbial
      communities, which include, in addition to the preferred yeast species they feed
      on, numerous harmful fungi and bacteria. We suggest that microbial ecology
      underlies many cases of copying in nature. 

PMID- 25375777
TI  - The evolution and genetics of virus host shifts.
AB  - Emerging viral diseases are often the product of a host shift, where a pathogen
      jumps from its original host into a novel species. Phylogenetic studies show that
      host shifts are a frequent event in the evolution of most pathogens, but why
      pathogens successfully jump between some host species but not others is only just
      becoming clear. The susceptibility of potential new hosts can vary enormously,
      with close relatives of the natural host typically being the most susceptible.
      Often, pathogens must adapt to successfully infect a novel host, for example by
      evolving to use different cell surface receptors, to escape the immune response,
      or to ensure they are transmitted by the new host. In viruses there are often
      limited molecular solutions to achieve this, and the same sequence changes are
      often seen each time a virus infects a particular host. These changes may come at
      a cost to other aspects of the pathogen's fitness, and this may sometimes prevent
      host shifts from occurring. Here we examine how these evolutionary factors affect
      patterns of host shifts and disease emergence. 

PMID- 25375779
TI  - Extending Theory, Rupturing Boundaries: Reproduction, Health, and Medicine Beyond
      North-South Binaries.

PMID- 25375778
TI  - Is 3-Tesla Gd-EOB-DTPA-enhanced MRI with diffusion-weighted imaging superior to
      64-slice contrast-enhanced CT for the diagnosis of hepatocellular carcinoma?
AB  - OBJECTIVES: To compare 64-slice contrast-enhanced computed tomography (CT) with 3
      Tesla magnetic resonance imaging (MRI) using Gd-EOB-DTPA for the diagnosis of
      hepatocellular carcinoma (HCC) and evaluate the utility of diffusion-weighted
      imaging (DWI) in this setting. METHODS: 3-phase-liver-CT was performed in fifty
      patients (42 male, 8 female) with suspected or proven HCC. The patients were
      subjected to a 3-Tesla-MRI-examination with Gd-EOB-DTPA and diffusion weighted
      imaging (DWI) at b-values of 0, 50 and 400 s/mm2. The apparent diffusion
      coefficient (ADC)-value was determined for each lesion detected in DWI. The
      histopathological report after resection or biopsy of a lesion served as the gold
      standard, and a surrogate of follow-up or complementary imaging techniques in
      combination with clinical and paraclinical parameters was used in unresected
      lesions. Diagnostic accuracy, sensitivity, specificity, and positive and negative
      predictive values were evaluated for each technique. RESULTS: MRI detected
      slightly more lesions that were considered suspicious for HCC per patient
      compared to CT (2.7 versus 2.3, respectively). ADC-measurements in HCC showed
      notably heterogeneous values with a median of 1.2+/-0.5*10-3 mm2/s (range from
      0.07+/-0.1 to 3.0+/-0.1*10-3 mm2/s). MRI showed similar diagnostic accuracy,
      sensitivity, and positive and negative predictive values compared to CT (AUC
      0.837, sensitivity 92%, PPV 80% and NPV 90% for MRI vs. AUC 0.798, sensitivity
      85%, PPV 79% and NPV 82% for CT; not significant). Specificity was 75% for both
      techniques. CONCLUSIONS: Our study did not show a statistically significant
      difference in detection in detection of HCC between MRI and CT. Gd-EOB-DTPA
      enhanced MRI tended to detect more lesions per patient compared to contrast
      enhanced CT; therefore, we would recommend this modality as the first-choice
      imaging method for the detection of HCC and therapeutic decisions. However,
      contrast-enhanced CT was not inferior in our study, so that it can be a useful
      image modality for follow-up examinations.

PMID- 25375780
TI  - Six-month outcomes from a randomized trial augmenting serotonin reuptake
      inhibitors with exposure and response prevention or risperidone in adults with
      obsessive-compulsive disorder.
AB  - OBJECTIVE: To compare outcomes after 6-month maintenance treatment of adults
      diagnosed with obsessive-compulsive disorder (OCD) based on DSM-IV criteria who
      responded to acute treatment with serotonin reuptake inhibitors (SRIs) augmented
      by exposure and response prevention (EX/RP) or risperidone. METHOD: A randomized
      trial was conducted at 2 academic sites from January 2007 through December 2012.
      In the acute phase, 100 patients on therapeutic SRI dose with at least moderate
      OCD severity were randomized to 8 weeks of EX/RP, risperidone, or pill placebo.
      Responders entered the 6-month maintenance phase, continuing the augmentation
      strategy they received acutely (n = 30 EX/RP, n = 8 risperidone). Independent
      evaluations were conducted every month. The main outcome was the Yale-Brown
      Obsessive Compulsive Scale (Y-BOCS). RESULTS: Intent-to-treat analyses indicated
      that, after 6-month maintenance treatment, EX/RP yielded OCD outcomes that were
      superior to risperidone (Y-BOCS = 10.95 vs 18.70; t40 = 2.76, P = .009); more
      patients randomized to EX/RP met response criteria (Y-BOCS decrease >= 25%: 70%
      vs 20%; P < .001) and achieved minimal symptoms (Y-BOCS <= 12: 50% vs 5%; P <
      .001). During maintenance, OCD severity decreased slightly in both conditions (Y
      BOCS decrease = 2.2 points, P = .020). Lower Y-BOCS at entry to maintenance was
      associated with more improvement in both conditions (r38 = 0.57, P < .001).
      CONCLUSIONS: OCD patients taking SRIs who responded to acute EX/RP or risperidone
      maintained their gains over 6-month maintenance. Because EX/RP patients improved
      more during acute treatment than risperidone-treated patients, and both
      maintained their gains during maintenance, EX/RP yielded superior outcomes 6
      months later. The findings that 50% of patients randomized to EX/RP had minimal
      symptoms at 6-month maintenance, a rate double that of prior studies, suggests
      that EX/RP maintenance helps maximize long-term outcome. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00389493.

PMID- 25375781
TI  - Positive allosteric modulators of 2-amino-3-(3-hydroxy-5-methylisoxazol-4
      yl)propionic acid receptors belonging to 4-cyclopropyl-3,4-dihydro-2h-1,2,4
      pyridothiadiazine dioxides and diversely chloro-substituted 4-cyclopropyl-3,4
      dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides.
AB  - Two 4-ethyl-substituted pyridothiadiazine dioxides belonging to alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric
      modulators were cocrystallized with the GluA2 ligand binding domain in order to
      decipher the impact of the position of the nitrogen atom on their binding mode at
      the AMPA receptors. The latter was found to be very similar to that of previously
      described benzothiadiazine-type AMPA receptor modulators. The affinity of the two
      compounds for the receptor was determined by isothermal titration calorimetry.
      Accordingly, the synthesis and biological evaluation of novel 4-cyclopropyl
      substituted pyridothiadiazine dioxides was performed and completed with the
      synthesis of the corresponding chloro-substituted 4-cyclopropyl-3,4-dihydro-2H
      benzothiadiazine 1,1-dioxides. The "8-aza" compound 32 was found to be the most
      potent pyridothiadiazine-type AMPA receptor potentiator in vitro, whereas the 7
      chloro-substituted compound 36c emerged as the most promising benzothiadiazine
      dioxide. Due to proper drug-likeness and low in vivo acute toxicity in mice, 36c
      was chosen for a more complete preclinical evaluation. The compound was able to
      easily cross the blood-brain barrier. In an in vivo object recognition test with
      CD1 mice, oral administration of 36c was found to significantly improve cognition
      performance at doses as low as 1 mg/kg. 

PMID- 25375782
TI  - Transcriptomic profiling of gametogenesis in triploid Pacific Oysters Crassostrea
      gigas: towards an understanding of partial sterility associated with triploidy.
AB  - BACKGROUND: Triploidy can occur in many animal species but is often lethal. Among
      invertebrates, amphibians and fishes, triploids are viable although often sterile
      or infertile. Most triploids of the Pacific oyster Crassostrea gigas are almost
      sterile (named "3nbeta") yet a low but significant proportion show an advanced
      gametogenesis (named "3nalpha"). These oysters thus constitute an interesting
      model to study the effect of triploidy on germ cell development. We used
      microarrays to compare the gonad transcriptomes of diploid 2n and the
      abovementioned triploid 3nbeta and 3nalpha male and female oysters throughout
      gametogenesis. RESULTS: All triploids displayed an upregulation of genes related
      to DNA repair and apoptosis and a downregulation of genes associated with cell
      division. The comparison of 3nalpha and 3nbeta transcriptomes with 2n revealed
      the likely involvement of a cell cycle checkpoint during mitosis in the
      successful but delayed development of gonads in 3nalpha individuals. In contrast,
      a disruption of sex differentiation mechanisms may explain the sterility of
      3nbeta individuals with 3nbeta females expressing male-specific genes and 3nbeta
      males expressing female-specific genes. CONCLUSIONS: The disruption of sex
      differentiation and mitosis may be responsible for the impaired gametogenesis of
      triploid Pacific oysters. The function of the numerous candidate genes identified
      in our study should now be studied in detail in order to elucidate their role in
      sex determination, mitosis/meiosis control, pachytene cell cycle checkpoint, and
      the control of DNA repair/apoptosis.

PMID- 25375783
TI  - Analysis of micro-rearrangements in 25 eukaryotic species pairs by SyntenyMapper.
AB  - High-quality mapping of genomic regions and genes between two organisms is an
      indispensable prerequisite for evolutionary analyses and comparative genomics.
      Existing approaches to this problem focus on either delineating orthologs or
      finding extended sequence regions of common evolutionary origin (syntenic
      blocks). We propose SyntenyMapper, a novel tool for refining predefined syntenic
      regions. SyntenyMapper creates a set of blocks with conserved gene order between
      two genomes and finds all minor rearrangements that occurred since the
      evolutionary split of the two species considered. We also present TrackMapper, a
      SyntenyMapper-based tool that allows users to directly compare genome features,
      such as histone modifications, between two organisms, and identify genes with
      highly conserved features. We demonstrate SyntenyMapper's advantages by
      conducting a large-scale analysis of micro-rearrangements within syntenic regions
      of 25 eukaryotic species. Unsurprisingly, the number and length of syntenic
      regions is correlated with evolutionary distance, while the number of micro
      rearrangements depends only on the size of the harboring region. On the other
      hand, the size of rearranged regions remains relatively constant regardless of
      the evolutionary distance between the organisms, implying a length constraint in
      the rearrangement process. SyntenyMapper is a useful software tool for both large
      scale and gene-centric genome comparisons. 

PMID- 25375784
TI  - Typhoid outbreak in Songkhla, Thailand 2009-2011: clinical outcomes,
      susceptibility patterns, and reliability of serology tests.
AB  - OBJECTIVE: To determine the clinical manifestations and outcomes, the reliability
      of Salmonella enterica serotype Typhi (S ser. Typhi) IgM and IgG rapid tests, and
      the susceptibility patterns and the response to treatment during the 2009-2011
      typhoid outbreak in Songkhla province in Thailand. METHOD: The medical records of
      children aged <15 years with S ser. Typhi bacteremia were analysed. The efficacy
      of the typhoid IgM and IgG rapid tests and susceptibility of the S ser. Typhi to
      the current main antibiotics used for typhoid (amoxicillin, ampicillin,
      cefotaxime, ceftriaxone, co-trimoxazole, and ciprofloxacin), were evaluated.
      RESULTS: S ser. Typhi bacteremia was found in 368 patients, and all isolated
      strains were susceptible to all 6 antimicrobials tested. Most of the patients
      were treated with ciprofloxacin for 7-14 days. The median time (IQR) of fever
      before treatment and duration of fever after treatment were 5 (4, 7) days and 4
      (3, 5) days, respectively. Complications of ascites, lower respiratory symptoms,
      anemia (Hct <30%), and ileal perforation were found in 7, 7, 22, and 1 patients,
      respectively. None of the patients had recurrent infection or died. The
      sensitivities of the typhoid IgM and IgG tests were 58.3% and 25.6% respectively,
      and specificities were 74.1% and 50.5%, respectively. CONCLUSION: Most of the
      patients were diagnosed at an early stage and treated with a good outcome. All S
      ser. Typhi strains were susceptible to standard first line antibiotic typhoid
      treatment. The typhoid IgM and IgG rapid tests had low sensitivity and moderate
      specificity.

PMID- 25375785
TI  - Concussion History in Adolescent Athletes with Attention-Deficit Hyperactivity
      Disorder.
AB  - Little is known about the rate of concussions in adolescents with attention
      deficit hyperactivity disorder (ADHD). We hypothesized that high school athletes
      with ADHD would report a greater history of concussion than students without
      ADHD. A total of 6529 adolescent and young adult student athletes, between the
      ages of 13 and 19 years (mean, 15.9; standard deviation, 1.3), completed a
      preseason health survey in 2010. Of those with ADHD, 26.1% reported a history of
      one or more concussions, compared to 17.1% of those without ADHD (p<0.00001; odds
      ratio [OR], 1.71). Stratified by gender, 27.0% of boys with ADHD reported a
      history of one or more concussions, compared to 20.0% of boys without ADHD
      (p<0.004; OR, 1.48), and 23.6% of girls with ADHD reported a history of one or
      more concussions, compared to 13.6% of girls without ADHD (p<0.003; OR, 1.97). Of
      those with ADHD, 9.8% reported a history of two or more concussions, compared to
      5.5% of those without ADHD (p<0.0003; OR, 1.87). Stratified by gender, 10.0% of
      boys with ADHD reported a history of two or more concussions, compared to 6.7% of
      boys without ADHD (p<0.033; OR, 1.54), and 9.1% of girls with ADHD reported a
      history of two or more concussions, compared to 3.8% of girls without ADHD
      (p<0.006; OR, 2.51). In this large-scale, retrospective survey study, boys and
      girls with ADHD were significantly more likely to report a history of concussion.
      Additional research is needed to determine whether students with ADHD are more
      susceptible to injury (i.e., have a lower threshold) or have different recovery
      trajectories.

PMID- 25375788
TI  - Examining the 10-year rebuilding dilemma for U.S. fish stocks.
AB  - Worldwide, fishery managers strive to maintain fish stocks at or above levels
      that produce maximum sustainable yields, and to rebuild overexploited stocks that
      can no longer support such yields. In the United States, rebuilding overexploited
      stocks is a contentious issue, where most stocks are mandated to rebuild in as
      short a time as possible, and in a time period not to exceed 10 years. Opponents
      of such mandates and related guidance argue that rebuilding requirements are
      arbitrary, and create discontinuities in the time and fishing effort allowed for
      stocks to rebuild due to differences in productivity. Proponents, however,
      highlight how these mandates and guidance were needed to curtail the continued
      overexploitation of these stocks by setting firm deadlines on rebuilding. Here we
      evaluate the statements made by opponents and proponents of the 10-year
      rebuilding mandate and related guidance to determine whether such points are
      technically accurate using a simple population dynamics model and a database of
      U.S. fish stocks to parameterize the model. We also offer solutions to many of
      the issues surrounding this mandate and its implementation by recommending some
      fishing mortality based frameworks, which meet the intent of the 10-year
      rebuilding requirement while also providing more flexibility. 

PMID- 25375789
TI  - Rad59-facilitated acquisition of Y' elements by short telomeres delays the onset
      of senescence.
AB  - Telomerase-negative yeasts survive via one of the two Rad52-dependent
      recombination pathways, which have distinct genetic requirements. Although the
      telomere pattern of type I and type II survivors is well characterized, the
      mechanistic details of short telomere rearrangement into highly evolved pattern
      observed in survivors are still missing. Here, we analyze immediate events taking
      place at the abruptly shortened VII-L and native telomeres. We show that short
      telomeres engage in pairing with internal Rap1-bound TG1-3-like tracts present
      between subtelomeric X and Y' elements, which is followed by BIR-mediated non
      reciprocal translocation of Y' element and terminal TG1-3 repeats from the donor
      end onto the shortened telomere. We found that choice of the Y' donor was not
      random, since both engineered telomere VII-L and native VI-R acquired Y' elements
      from partially overlapping sets of specific chromosome ends. Although short
      telomere repair was associated with transient delay in cell divisions, Y'
      translocation on native telomeres did not require Mec1-dependent checkpoint.
      Furthermore, the homeologous pairing between the terminal TG1-3 repeats at VII-L
      and internal repeats on other chromosome ends was largely independent of Rad51,
      but instead it was facilitated by Rad59 that stimulates Rad52 strand annealing
      activity. Therefore, Y' translocation events taking place during presenescence
      are genetically separable from Rad51-dependent Y' amplification process that
      occurs later during type I survivor formation. We show that Rad59-facilitated Y'
      translocations on X-only telomeres delay the onset of senescence while preparing
      ground for type I survivor formation. 

PMID- 25375790
TI  - Behavior change pathways to voluntary medical male circumcision: narrative
      interviews with circumcision clients in Zambia.
AB  - As an HIV prevention strategy, the scale-up of voluntary medical male
      circumcision (VMMC) is underway in 14 countries in Africa. For prevention impact,
      these countries must perform millions of circumcisions in adolescent and adult
      men before 2015. Although acceptability of VMMC in the region is well documented
      and service delivery efforts have proven successful, countries remain behind in
      meeting circumcision targets. A better understanding of men's VMMC-seeking
      behaviors and experiences is needed to improve communication and interventions to
      accelerate uptake. To this end, we conducted semi-structured interviews with 40
      clients waiting for surgical circumcision at clinics in Zambia. Based on Stages
      of Change behavioral theory, men were asked to recount how they learned about
      adult circumcision, why they decided it was right for them, what they feared
      most, how they overcame their fears, and the steps they took to make it to the
      clinic that day. Thematic analysis across all cases allowed us to identify key
      behavior change triggers while within-case analysis elucidated variants of one
      predominant behavior change pattern. Major stages included: awareness and
      critical belief adjustment, norming pressures and personalization of advantages,
      a period of fear management and finally VMMC-seeking. Qualitative comparative
      analysis of ever-married and never-married men revealed important similarities
      and differences between the two groups. Unprompted, 17 of the men described one
      to four failed prior attempts to become circumcised. Experienced more frequently
      by older men, failed VMMC attempts were often due to service-side barriers.
      Findings highlight intervention opportunities to increase VMMC uptake. Reaching
      uncircumcised men via close male friends and female sex partners and tailoring
      messages to stage-specific concerns and needs would help accelerate men's
      movement through the behavior change process. Expanding service access is also
      needed to meet current demand. Improving clinic efficiencies and introducing time
      saving procedures and advance scheduling options should be considered. 

PMID- 25375791
TI  - Robotically assisted amniotic membrane transplant surgery.

PMID- 25375792
TI  - Attitudes of serodiscordant couples towards antiretroviral-based HIV prevention
      strategies in Kenya: a qualitative study.
AB  - This qualitative study aims to gain in-depth information about the attitudes of
      HIV-serodiscordant couples towards two new methods of HIV prevention; Pre
      Exposure Prophylaxis and Treatment as Prevention, both of which have been
      recently recommended by the World Health Organisation. Semi-structured interviews
      were conducted with 38 individuals in a serodiscordant relationship in Western
      Kenya. Topic guides were used to elicit information on perceived benefits,
      concerns, and preferences towards Treatment as Prevention and Pre-Exposure
      Prophylaxis. Data evaluation and thematic generation were developed using
      framework analysis. Results suggest that the majority of participants,
      irrespective of gender and HIV status, found Treatment as Prevention the more
      acceptable strategy. Key factors influencing this decision were HIV-negative
      participants' limited motivation to take prophylactic antiretrovirals and the
      likely health improvements Treatment as Prevention offers HIV-positive partners.
      However, issues were raised concerning the likelihood of low concurrent condom
      use and poor medication adherence when using these preventative approaches. It
      was concluded that the adoption of Treatment as Prevention as a method of HIV
      control in Kenya is likely to be more readily accepted by serodiscordant couples
      than Pre-exposure Prophylaxis. However, future implementation of either strategy
      would require measures to address the possibility of risk compensation and poor
      adherence.

PMID- 25375794
TI  - Assessing productivity among university academics and scientific researchers.

PMID- 25375796
TI  - CBCT special issue.

PMID- 25375795
TI  - ARTIST: high-resolution genome-wide assessment of fitness using transposon
      insertion sequencing.
AB  - Transposon-insertion sequencing (TIS) is a powerful approach for deciphering
      genetic requirements for bacterial growth in different conditions, as it enables
      simultaneous genome-wide analysis of the fitness of thousands of mutants.
      However, current methods for comparative analysis of TIS data do not adjust for
      stochastic experimental variation between datasets and are limited to
      interrogation of annotated genomic elements. Here, we present ARTIST, an
      accessible TIS analysis pipeline for identifying essential regions that are
      required for growth under optimal conditions as well as conditionally essential
      loci that participate in survival only under specific conditions. ARTIST uses
      simulation-based normalization to model and compensate for experimental noise,
      and thereby enhances the statistical power in conditional TIS analyses. ARTIST
      also employs a novel adaptation of the hidden Markov model to generate
      statistically robust, high-resolution, annotation-independent maps of fitness
      linked loci across the entire genome. Using ARTIST, we sensitively and
      comprehensively define Mycobacterium tuberculosis and Vibrio cholerae loci
      required for host infection while limiting inclusion of false positive loci.
      ARTIST is applicable to a broad range of organisms and will facilitate TIS-based
      dissection of pathways required for microbial growth and survival under a
      multitude of conditions. 

PMID- 25375797
TI  - The phenology of ticks and the effects of long-term prescribed burning on tick
      population dynamics in southwestern Georgia and northwestern Florida.
AB  - Some tick populations have increased dramatically in the past several decades
      leading to an increase in the incidence and emergence of tick-borne diseases.
      Management strategies that can effectively reduce tick populations while better
      understanding regional tick phenology is needed. One promising management
      strategy is prescribed burning. However, the efficacy of prescribed burning as a
      mechanism for tick control is unclear because past studies have provided
      conflicting data, likely due to a failure of some studies to simulate operational
      management scenarios and/or account for other predictors of tick abundance.
      Therefore, our study was conducted to increase knowledge of tick population
      dynamics relative to long-term prescribed fire management. Furthermore, we
      targeted a region, southwestern Georgia and northwestern Florida (USA), in which
      little is known regarding tick dynamics so that basic phenology could be
      determined. Twenty-one plots with varying burn regimes (burned surrounded by
      burned [BB], burned surrounded by unburned [BUB], unburned surrounded by burned
      [UBB], and unburned surrounded by unburned [UBUB]) were sampled monthly for two
      years while simultaneously collecting data on variables that can affect tick
      abundance (e.g., host abundance, vegetation structure, and micro- and macro
      climatic conditions). In total, 47,185 ticks were collected, of which, 99% were
      Amblyomma americanum, 0.7% were Ixodes scapularis, and fewer numbers of Amblyomma
      maculatum, Ixodes brunneus, and Dermacentor variabilis. Monthly seasonality
      trends were similar between 2010 and 2011. Long-term prescribed burning
      consistently and significantly reduced tick counts (overall and specifically for
      A. americanum and I. scapularis) regardless of the burn regimes and variables
      evaluated. Tick species composition varied according to burn regime with A.
      americanum dominating at UBUB, A. maculatum at BB, I. scapularis at UBB, and a
      more even composition at BUB. These data indicate that regular prescribed burning
      is an effective tool for reducing tick populations and ultimately may reduce risk
      of tick-borne disease. 

PMID- 25375799
TI  - Cost savings and enhanced hospice enrollment with a home-based palliative care
      program implemented as a hospice-private payer partnership.
AB  - BACKGROUND: In the United States, 5% of the population is responsible for nearly
      half of all health care expenditures, with a large concentration of spending
      driven by individuals with expensive chronic conditions in their last year of
      life. Outpatient palliative care under the Medicare Hospice Benefit excludes a
      large proportion of the chronically ill and there is widespread recognition that
      innovative strategies must be developed to meet the needs of the seriously ill
      while reducing costs. OBJECTIVE: This study aimed to evaluate the impact of a
      home-based palliative care program, implemented through a hospice-private payer
      partnership, on health care costs and utilization. METHODS: This was a
      prospective, observational database study where insurance enrollment and claims
      data were analyzed. The study population consisted of Home Connections (HC)
      program patients enrolled between January 1, 2010 and December 31, 2012 who
      subsequently expired (n=149) and who were also Independent Health members. A
      control group (n=537) was derived using propensity-score matching. The primary
      outcome variable was overall costs within the last year of life. Costs were also
      examined at six months, three months, one month, and two weeks. Inpatient,
      outpatient, ancillary, professional, and pharmacy costs were compared between the
      two groups. Medical service utilization and hospice enrollment and length of stay
      were also evaluated. RESULTS: Cost savings were apparent in the last three months
      of life-$6,804 per member per month (PMPM) cost for palliative care participants
      versus $10,712 for usual care. During the last two weeks of life, total allowed
      PMPM was $6,674 versus $13,846 for usual care. Enhanced hospice entry (70% versus
      25%) and longer length of stay in hospice (median 34 versus 9 days) were
      observed. CONCLUSIONS: Palliative care programs partnered with community hospice
      providers may achieve cost savings while helping provide care across the
      continuum.

PMID- 25375798
TI  - Virulence diversity among bacteremic Aeromonas isolates: ex vivo, animal, and
      clinical evidences.
AB  - BACKGROUND: The objective of this study was to compare virulence among different
      Aeromonas species causing bloodstream infections. METHODOLOGY/PRINCIPAL FINDINGS:
      Nine of four species of Aeromonas blood isolates, including A. dhakensis, A.
      hydrophila, A. veronii and A. caviae were randomly selected for analysis. The
      species was identified by the DNA sequence matching of rpoD. Clinically, the
      patients with A. dhakensis bacteremia had a higher sepsis-related mortality rate
      than those with other species (37.5% vs. 0%, P = 0.028). Virulence of different
      Aeromonas species were tested in C. elegans, mouse fibroblast C2C12 cell line and
      BALB/c mice models. C. elegans fed with A. dhakensis and A. caviae had the lowest
      and highest survival rates compared with other species, respectively (all P
      values <0.0001). A. dhakensis isolates also exhibited more cytotoxicity in C2C12
      cell line (all P values <0.0001). Fourteen-day survival rate of mice
      intramuscularly inoculated with A. dhakensis was lower than that of other species
      (all P values <0.0001). Hemolytic activity and several virulence factor genes
      were rarely detected in the A. caviae isolates. CONCLUSIONS/SIGNIFICANCE:
      Clinical data, ex vivo experiments, and animal studies suggest there is virulence
      variation among clinically important Aeromonas species.

PMID- 25375800
TI  - Detection of UV-induced mutagenic thymine dimer using graphene oxide.
AB  - In this paper, we report for the first time that graphene oxide (GO) can interact
      with mutagenic DNA but not intact DNA. After UV-irradiated fluorophore-linked DNA
      containing thymine repeats was mixed with GO, a decrease in fluorescence was
      observed in a time-dependent manner. In contrast, no fluorescence change was
      observed with intact DNA, indicating that UV irradiation of DNA resulted in the
      formation of mutagenic bases. Because GO is known to act as a fluorescence
      quencher, the decreased fluorescence implies adsorption of the UV-irradiated DNA
      onto GO. It appears that the decreased fluorescence might result from the greater
      accessibility of hydrophobic methyl groups and phenyl rings of thymine dimers to
      GO and from deformed DNA structures with less effective charge shielding under
      salt-containing conditions. Using this affinity of GO for mutagenic DNA, we could
      detect UV-irradiated DNA at concentrations as low as 100 pM. We were also able to
      analyze the ability of phototoxic drugs to catalyze the formation of mutagens
      under UV irradiation with GO. Because our method is highly sensitive and feasible
      and does not require the pretreatment of DNA, we propose that it could accelerate
      the screening of potential phototoxic drug candidates that would be able to
      sensitize mutagenic dsDNA. 

PMID- 25375801
TI  - The Apelin-APJ axis is an endogenous counterinjury mechanism in experimental
      acute lung injury.
AB  - BACKGROUND: Although the mechanisms and pathways mediating ARDS have been studied
      extensively, less attention has been given to the mechanisms and pathways that
      counteract injury responses. This study found that the apelin-APJ pathway is an
      endogenous counterinjury mechanism that protects against ARDS. METHODS: Using a
      rat model of oleic acid (OA)-induced ARDS, the effects of ARDS on apelin and APJ
      receptor expressions and on APJ receptor binding capacity were examined. The
      protective effect of activating the apelin-APJ pathway against OA- or
      lipopolysaccharide (LPS)-induced ARDS was evaluated. RESULTS: ARDS was coupled to
      upregulations of the apelin and APJ receptor. Rats with OA-induced ARDS had
      higher lung tissue levels of apelin proprotein and APJ receptor expressions;
      elevated plasma, BAL fluid (BALF), and lung tissue levels of apelin-36 and apelin
      12/13; and an increased apelin-APJ receptor binding capacity. Upregulation of the
      apelin-APJ system has important pathophysiologic function. Stimulation of the
      apelin-APJ signaling using receptor agonist apelin-13 alleviated, whereas
      inhibition of the apelin-APJ signaling using receptor antagonist [Ala]-apelin-13
      exacerbated, OA-induced lung pathologies, extravascular lung water accumulation,
      capillary-alveolar leakage, and hypoxemia. The APJ receptor agonist inhibited,
      and the APJ receptor antagonist augmented, OA-induced lung tissue and BALF levels
      of tumor necrosis factor-alpha and monocyte chemoattractant protein-1, and plasma
      and lung tissue levels of malondialdehyde. Postinjury treatment with apelin-13
      alleviated lung inflammation and injury and improved oxygenation in OA- and LPS
      induced lung injury. CONCLUSIONS: The apelin-APJ signaling pathway is an
      endogenous anti-injury and organ-protective mechanism that is activated during
      ARDS to counteract the injury response and to prevent uncontrolled lung injury.

PMID- 25375802
TI  - Two-dimensional metal-chalcogenide films in tunable optical microcavities.
AB  - Integration of quasi-two-dimensional (2D) films of metal-chalcogenides in optical
      microcavities permits new photonic applications of these materials. Here we
      present tunable microcavities with monolayer MoS2 or few monolayer GaSe films. We
      observe significant modification of spectral and temporal properties of
      photoluminescence (PL): PL is emitted in spectrally narrow and wavelength-tunable
      cavity modes with quality factors up to 7400; a 10-fold PL lifetime shortening is
      achieved, a consequence of Purcell enhancement of the spontaneous emission rate. 

PMID- 25375803
TI  - Clinicopathologic characteristics of typical medullary breast carcinoma: a
      retrospective study of 117 cases.
AB  - PURPOSE: This study analyzed the clinicopathologic characteristics of typical
      medullary breast carcinoma (TMBC) in a cohort of Chinese patients. METHODS: We
      conducted a retrospective review of clinical data including general information,
      pathologic results, treatment regimens, and patient survival in cases of TMBC
      diagnosed between February 2004 and April 2011. RESULTS: A total of 117 patients
      were enrolled, with a median age of 52 years (range, 28~92 years). Stage I and II
      disease accounted for 31.6% and 61.6% of the cases, respectively. Hormonal
      receptor negative disease (estrogen receptor negative, 68.4%; progestogen
      receptor negative, 86.3%) was more prevalent in this population. Human epidermal
      growth factor receptor-2 (HER-2) positivity was 20.5%, while equivocal and HER-2
      negative cases represented 16.2% and 63.2% of the cohort. The triple-negative,
      luminal, and HER-2 overexpressing subtypes constituted 44.4%, 31.6%, and 15.4% of
      the cases, respectively. The various TMBC subtypes showed no differences
      regarding tumor size, rates of lymph node(s) metastasis, TNM staging, treatment
      regimens, and 2-year recurrence rates. However, patients with triple-negative
      disease were more likely to be younger, when compared to those with luminal
      disease (P = 0.002). At a median follow-up of 56 months (range, 2-112 months),
      the 2-year disease-free survival and overall survival rates were 99.1% and 98.2%,
      respectively. CONCLUSION: Early stage disease dominated the study cohort, and at
      two years after surgery, recurrence was extremely low. The heterogeneity of
      molecular subtypes was clearly shown, and no apparent differences were found
      among the clinicopathologic characteristics of the triple-negative, luminal, and
      HER-2 overexpressing subtypes.

PMID- 25375804
TI  - Intermediate-volatility organic compounds: a large source of secondary organic
      aerosol.
AB  - Secondary organic aerosol (SOA) is a major component of atmospheric fine particle
      mass. Intermediate-volatility organic compounds (IVOCs) have been proposed to be
      an important source of SOA. We present a comprehensive analysis of atmospheric
      IVOC concentrations and their SOA production using measurements made in Pasadena,
      California during the California at the Nexus of Air Quality and Climate Change
      (CalNex) study. The campaign-average concentration of primary IVOCs was 6.3 +/-
      1.9 MUg m(-3) (average +/- standard deviation), which is comparable to the
      concentration of organic aerosol but only 7.4 +/- 1.2% of the concentration of
      speciated volatile organic compounds. Only 8.6 +/- 2.2% of the mass of the
      primary IVOCs was speciated. Almost no weekend/weekday variation in the ambient
      concentration of both speciated and total primary IVOCs was observed, suggesting
      that petroleum-related sources other than on-road diesel vehicles contribute
      substantially to the IVOC emissions. Primary IVOCs are estimated to produce about
      30% of newly formed SOA in the afternoon during CalNex, about 5 times that from
      single-ring aromatics. The importance of IVOCs in SOA formation is expected to be
      similar in many urban environments. 

PMID- 25375805
TI  - Conjunctival rhinosporidiosis.

PMID- 25375810
TI  - Lab-in-a-syringe using gold nanoparticles for rapid immunosensing of protein
      biomarkers.
AB  - We have developed a paper and gold nanoparticle (AuNP)-based lab-in-a-syringe
      (LIS) for immunosensing of biomarkers. This simple diagnostic device features
      simultaneous sampling and vertical-flow operation, which means that unlike
      typical immunosensors, it does not suffer from any delay between sampling and
      detection. It can handle large-volume, low-concentration samples for analysis in
      diverse applications (e.g. biomedical, environmental, food, etc.). Furthermore,
      its operating range for sample concentration can be tuned by simply changing the
      volume of the syringed sample, which enables on-demand limits of detection (LOD).
      The LIS contains two nitrocellulose pads: the conjugate pad (which captures the
      analyte) and the detection pad (which signals the presence of the captured
      analyte) both embedded into reusable plastic cartridges. We demonstrated its
      efficiency in detecting human IgG (HIgG) (LOD: 1.0 ng mL(-1)) and prostate
      specific antigen (PSA) (spiked urine samples; LOD: 1.9 ng mL(-1)). In the field,
      the LIS can be used for complete on-site analysis or to obtain partially analyzed
      samples (AuNPs with captured analyte) for subsequent detailed testing in
      specialized laboratories. 

PMID- 25375814
TI  - Revisiting electroaccepting and electrodonating powers: proposals for local
      electrophilicity and local nucleophilicity descriptors.
AB  - The electrophilicity index, MU(2)/2eta, where MU is the chemical potential and
      eta is the hardness, has been defined by Parr, Von Szentpaly, and Liu (J. Am.
      Chem. Soc., 1999, 121, 1922) as the lowering in energy of an electronic system
      during a process in which the chemical potential of the system raises from MU to
      zero, accepting -MU/eta electrons. In this work, it is shown that the
      electrophilicity index is also a rational choice for measuring nucleophilicity.
      Indeed, within the grand canonical ensemble, when the chemical potential of a
      system increases from MU to zero, the system gives away MU/eta electrons. During
      the process, the variation of the grand potential is MU(2)/2eta. Additionally,
      through the use of a second order Taylor series expansion of the density as a
      function of the number of electrons, at constant external potential, which
      depends on the Fukui function and the dual descriptor, the local electrophilicity
      is defined as the actual variation of the electron density when the system
      acquires -MU/eta electrons, while the local nucleophilicity is similarly defined
      for the case when the system loses MU/eta electrons. 

PMID- 25375813
TI  - Right-side propensity of cardiogenic emboli in acute ischemic stroke with atrial
      fibrillation.
AB  - OBJECTIVES: We attempted to determine the propensity for sidedness of cardiogenic
      emboli associated with atrial fibrillation (AF) by comparing the sides on which
      microembolic signals (MES) were detected via transcranial Doppler (TCD)
      monitoring and the location of infarcts on magnetic resonance imaging. DESIGN:
      Patients with AF on Holter monitoring and MES on TCD monitoring were selected
      from an ischemic stroke registry. Patients with prosthetic valves or
      cerebral/carotid artery stenosis were excluded. RESULTS: By TCD monitoring of 30
      patients, 78 MES were detected: 47 on the right and 31 on the left side (60.3%
      vs. 39.7%, p < 0.01, chi-square test). Among 21 patients who had middle or
      anterior cerebral artery (MCA/ACA) territory infarcts, 16 had right-side-dominant
      infarcts and 5 patients had left-side-dominant infarcts (76.2% vs. 23.8%, p <
      0.01, chi-square test). The median infarct volume on the right side was 16.2
      (3.18-75.4) ml, while that of left side was 1.2 (0.25-5.05) ml (p < 0.01, Mann
      Whitney U test). CONCLUSION: This study demonstrated the existence of a right
      side propensity of cardiogenic emboli and the larger infarct volume of right-side
      MCA/ACA stroke in patients with AF. These results can be attributed to anatomical
      differences between the innominate and the left common carotid artery.

PMID- 25375815
TI  - Measurement of sterigmatocystin concentrations in urine for monitoring the
      contamination of cattle feed.
AB  - This study aimed (1) at determining the levels of the fungal toxin
      sterigmatocystin (STC) in the feed and urine of cattle and (2) at evaluating the
      effects of supplementing the feed with a mycotoxin adsorbent (MA) on STC
      concentrations in urine. Two herds of female Japanese Black cattle were used in
      this study. The cattle in each herd were fed a standard ration containing rice
      straw from different sources and a standard concentrate; two groups of cattle
      from each herd (n = six per group) received the commercial MA, mixed with the
      concentrate or given as top-dressing, whereas a third group received no
      supplement and served as control. Urine and feed samples were collected at
      various time points throughout the experiment. STC concentrations were measured
      using liquid chromatography-tandem mass spectrometry (LC-TMS). STC concentrations
      in straw were higher in Herd 1 (range 0.15-0.24 mg/kg DM) than in Herd 2 (range
      <0.01-0.06 mg/kg DM). In Herd 1, STC concentrations in urine significantly
      declined 2 weeks after replacing the contaminated feed, whereas MA
      supplementation had no effect. In conclusion, mycotoxins in urine samples are
      useful biological markers for monitoring the systemic exposure of cattle to
      multiple mycotoxins, as well as evaluating the effectiveness of interventions. 

PMID- 25375816
TI  - Statistical computations underlying the dynamics of memory updating.
AB  - Psychophysical and neurophysiological studies have suggested that memory is not
      simply a carbon copy of our experience: Memories are modified or new memories are
      formed depending on the dynamic structure of our experience, and specifically, on
      how gradually or abruptly the world changes. We present a statistical theory of
      memory formation in a dynamic environment, based on a nonparametric
      generalization of the switching Kalman filter. We show that this theory can
      qualitatively account for several psychophysical and neural phenomena, and
      present results of a new visual memory experiment aimed at testing the theory
      directly. Our experimental findings suggest that humans can use temporal
      discontinuities in the structure of the environment to determine when to form new
      memory traces. The statistical perspective we offer provides a coherent account
      of the conditions under which new experience is integrated into an old memory
      versus forming a new memory, and shows that memory formation depends on
      inferences about the underlying structure of our experience. 

PMID- 25375817
TI  - Malignant struma ovarii: a population-level analysis of a large series of 68
      patients.
AB  - BACKGROUND: Malignant struma ovarii (MSO) is a germ cell tumor of the ovary
      histologically identical to differentiated thyroid cancers. There is a paucity of
      data on this neoplasm, with fewer than 200 reported cases. The primary objective
      of this study was to examine the survival rate of women diagnosed with MSO using
      data from the Surveillance, Epidemiology, and End RESULTS (SEER) database.
      Secondary objectives were to describe the demographic, clinical, pathologic, and
      treatment characteristics of this population. METHODS: A retrospective analysis
      was performed of prospectively collected cancer registry data. A total of 68
      patients were identified in the SEER database, 1973-2011. The chi-square test,
      Student's t-test, and Kaplan-Meier curves were employed for data analyses.
      RESULTS: All 68 patients were females with a mean age at diagnosis of 43.0 years.
      Nearly 33% underwent unilateral oophorectomy, 28.6% bilateral oophorectomy, and
      28.6% oophorectomy and omentectomy, and 4.8% were treated with debulking surgery.
      Pelvic radiation was administered to 12.3% of patients. The mean tumor size was
      52.8 mm; 80% of malignant struma ovarii were SEER staged as local. Overall
      survival rates at 5, 10, and 20 years were 96.7%, 94.3%, and 84.9% respectively.
      Among the patients, there were six deaths recorded; only one was attributed to
      MSO. Six individuals (8.8%) had a concomitant or subsequent diagnosis of thyroid
      cancer. Four patients underwent total thyroidectomy, three patients had
      radioactive iodine, and one patient underwent external beam radiation. Two thirds
      of thyroid cancers extended outside the thyroid gland. All six patients with
      thyroid cancer were alive at the end of follow-up. CONCLUSIONS: It was observed
      that patients with malignant struma ovarii had an excellent disease-specific
      survival rate, regardless of the management strategy employed. However, MSO
      patients had a high risk for developing aggressive thyroid cancers. Therefore,
      MSO patients may benefit from routine thyroid imaging once the diagnosis of MSO
      is established.

PMID- 25375818
TI  - Acidification Activates Toxoplasma gondii Motility and Egress by Enhancing
      Protein Secretion and Cytolytic Activity.
AB  - Pathogenic microbes rely on environmental cues to initiate key events during
      infection such as differentiation, motility, egress and invasion of cells or
      tissues. Earlier investigations showed that an acidic environment activates
      motility of the protozoan parasite T. gondii. Conversely, potassium ions, which
      are abundant in the intracellular milieu that bathes immotile replicating
      parasites, suppress motility. Since motility is required for efficient parasite
      cell invasion and egress we sought to better understand its regulation by
      environmental cues. We found that low pH stimulates motility by triggering Ca2+
      dependent secretion of apical micronemes, and that this cue is sufficient to
      overcome suppression by potassium ions and drive parasite motility, cell invasion
      and egress. We also discovered that acidification promotes membrane binding and
      cytolytic activity of perforin-like protein 1 (PLP1), a pore-forming protein
      required for efficient egress. Agents that neutralize pH reduce the efficiency of
      PLP1-dependent perforation of host membranes and compromise egress. Finally,
      although low pH stimulation of microneme secretion promotes cell invasion, it
      also causes PLP1-dependent damage to host cells, suggesting a mechanism by which
      neutral extracellular pH subdues PLP1 activity to allow cell invasion without
      overt damage to the target cell. These findings implicate acidification as a
      signal to activate microneme secretion and confine cytolytic activity to egress
      without compromising the viability of the next cell infected. 

PMID- 25375819
TI  - Canine Mesenchymal Stem Cell Potential and the Importance of Dog Breed:
      Implication for Cell-Based Therapies.
AB  - The study of canine bone marrow-derived mesenchymal stem cells (MSCs) has a
      prominent position in veterinary cell-based applications. Yet the plethora of
      breeds, their different life spans, and interbreed variations provide unclearness
      on what can be achieved specifically by such therapies. In this study, we
      compared a set of morphological, physiological, and genetic markers of MSCs
      derived from large dog breeds, namely, Border collie, German shepherd, Labrador,
      Malinois, Golden retriever, and Hovawart. We compared colony-forming units (CFUs)
      assay, population doubling time (PDT), senescence-associated beta-galactosidase
      (SA-beta-gal) activity, telomere length, and gene expression of MSCs, as well as
      the ability of cells to differentiate to osteogenic, adipogenic, and chondrogenic
      phenotypes. The influence of the culture media alpha-MEM, low-glucose DMEM, and
      high-glucose DMEM, used in cell isolation and expansion, was investigated in the
      presence and absence of basic fibroblast growth factor (bFGF). Initial cell yield
      was not affected by culturing medium, but MSCs expanded best in alpha-MEM
      supplemented with bFGF. After isolation, the number of MSCs was similar among
      breeds--as shown by equivalent CFUs--except in the Hovawart samples, which had
      fivefold less CFU. Telomere lengths were similar among breeds. MSCs divided
      actively only for 4 weeks in culture (PDT = ~50 h/division), except Border collie
      cells divided for a longer time than cells from other groups. The percentage of
      senescent cells increased linearly in all breeds with time, with a faster rate in
      German shepherd, Labrador, and Golden retriever. Border collie cells underwent
      efficient osteogenic differentiation, Hovawart cells performed the best in
      chondrogenic differentiation, and Labrador cells in both, while German shepherd
      cells had the lower differentiation potential. MSCs from all breeds preserved the
      same adipogenic differentiation potential. In conclusion, despite variations,
      isolated MSCs can be expanded and differentiated in vitro, and all breeds are
      eligible for MSC-based therapies.

PMID- 25375820
TI  - Nimesulide improves the symptomatic and disease modifying effects of leflunomide
      in collagen induced arthritis.
AB  - Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid
      arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of
      rheumatoid arthritis. Herein we studied the influence of nimesulide and
      leflunomide combination in terms of disease symptoms and progression using
      collagen-induced arthritis model in mice, as a model for rheumatoid arthritis.
      Collagen induced arthritis was induced by immunization with type II collagen.
      Assessment of joint stiffness and articular hyperalgesia were evaluated using a
      locomotor activity cage and the Hargreaves method, respectively. Disease
      progression was assessed via arthritic index scoring, X-ray imaging,
      myeloperoxidase enzyme activity and histopathologic examination. Nimesulide
      induced only transient symptomatic alleviation on the top of decreased leucocytic
      infiltration compared to arthritis group. However, nimesulide alone failed to
      induce any significant improvement in the radiological or pathological disease
      progression. Leflunomide alone moderately alleviates the symptoms of arthritis
      and moderately retarded the radiological and pathological disease progression.
      Combination of nimesulide and leflunomide significantly improved symptomatic
      (analgesia and joint stiffness) and arthritic disease progression (radiological,
      pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis
      animal model. 

PMID- 25375821
TI  - Size does matter: an integrative in vivo-in silico approach for the treatment of
      critical size bone defects.
AB  - Although bone has a unique restorative capacity, i.e., it has the potential to
      heal scarlessly, the conditions for spontaneous bone healing are not always
      present, leading to a delayed union or a non-union. In this work, we use an
      integrative in vivo-in silico approach to investigate the occurrence of non
      unions, as well as to design possible treatment strategies thereof. The gap size
      of the domain geometry of a previously published mathematical model was enlarged
      in order to study the complex interplay of blood vessel formation, oxygen supply,
      growth factors and cell proliferation on the final healing outcome in large bone
      defects. The multiscale oxygen model was not only able to capture the essential
      aspects of in vivo non-unions, it also assisted in understanding the underlying
      mechanisms of action, i.e., the delayed vascularization of the central callus
      region resulted in harsh hypoxic conditions, cell death and finally disrupted
      bone healing. Inspired by the importance of a timely vascularization, as well as
      by the limited biological potential of the fracture hematoma, the influence of
      the host environment on the bone healing process in critical size defects was
      explored further. Moreover, dependent on the host environment, several treatment
      strategies were designed and tested for effectiveness. A qualitative
      correspondence between the predicted outcomes of certain treatment strategies and
      experimental observations was obtained, clearly illustrating the model's
      potential. In conclusion, the results of this study demonstrate that due to the
      complex non-linear dynamics of blood vessel formation, oxygen supply, growth
      factor production and cell proliferation and the interactions thereof with the
      host environment, an integrative in silico-in vivo approach is a crucial tool to
      further unravel the occurrence and treatments of challenging critical sized bone
      defects.

PMID- 25375822
TI  - Construction of 3D micropatterned surfaces with wormlike and superhydrophilic PEG
      brushes to detect dysfunctional cells.
AB  - Detection of dysfunctional and apoptotic cells plays an important role in
      clinical diagnosis and therapy. To develop a portable and user-friendly platform
      for dysfunctional and aging cell detection, we present a facile method to
      construct 3D patterns on the surface of styrene-b-(ethylene-co-butylene)-b
      styrene elastomer (SEBS) with poly(ethylene glycol) brushes. Normal red blood
      cells (RBCs) and lysed RBCs (dysfunctional cells) are used as model cells. The
      strategy is based on the fact that poly(ethylene glycol) brushes tend to interact
      with phosphatidylserine, which is in the inner leaflet of normal cell membranes
      but becomes exposed in abnormal or apoptotic cell membranes. We demonstrate that
      varied patterned surfaces can be obtained by selectively patterning atom transfer
      radical polymerization (ATRP) initiators on the SEBS surface via an aqueous-based
      method and growing PEG brushes through surface-initiated atom transfer radical
      polymerization. The relatively high initiator density and polymerization
      temperature facilitate formation of PEG brushes in high density, which gives
      brushes worm-like morphology and superhydrophilic property; the tendency of
      dysfunctional cells adhered on the patterned surfaces is completely different
      from well-defined arrays of normal cells on the patterned surfaces, providing a
      facile method to detect dysfunctional cells effectively. The PEG-patterned
      surfaces are also applicable to detect apoptotic HeLa cells. The simplicity and
      easy handling of the described technique shows the potential application in
      microdiagnostic devices. 

PMID- 25375823
TI  - Late removal of retrievable caval filters.
AB  - The advent of retrievable caval filters was a game changer in the sense, that the
      previously irreversible act of implanting a medical device into the main venous
      blood stream of the body requiring careful evaluation of the pros and cons prior
      to execution suddenly became a "reversible" procedure where potential hazards in
      the late future of the patient lost most of their weight at the time of decision
      making. This review was designed to assess the rate of success with late
      retrieval of so called retrievable caval filters in order to get some indication
      about reasonable implant duration with respect to relatively "easy" implant
      removal with conventional means, i.e., catheters, hooks and lassos. A PubMed
      search (www.pubmed.gov) was performed with the search term "cava filter retrieval
      after 30 days clinical", and 20 reports between 1994 and 2013 dealing with late
      retrieval of caval filters were identified, covering approximately 7,000 devices
      with 600 removed filters. The maximal duration of implant reported is 2,599 days
      and the maximal implant duration of removed filters is also 2,599 days. The
      maximal duration reported with standard retrieval techniques, i.e., catheter,
      hook and/or lasso, is 475 days, whereas for the retrievals after this period more
      sophisticated techniques including lasers, etc. were required. The maximal
      implant duration for series with 100% retrieval accounts for 84 days, which is
      equivalent to 12 weeks or almost 3 months. We conclude that retrievable caval
      filters often become permanent despite the initial decision of temporary use.
      However, such "forgotten" retrievable devices can still be removed with a great
      chance of success up to three months after implantation. Conventional
      percutaneous removal techniques may be sufficient up to sixteen months after
      implantation whereas more sophisticated catheter techniques have been shown to be
      successful up to 83 months or more than seven years of implant duration. Tilting,
      migrating, or misplaced devices should be removed early on, and replaced if
      indicated with a device which is both, efficient and retrievable. 

PMID- 25375824
TI  - Conformations of a model cyclic hexapeptide, CYIQNC: (1)H-NMR and molecular
      dynamics studies.
AB  - Solution conformation of the cyclic hexapeptide sequence, [cyclo-S-Cys-Tyr-Ile
      Gln-Asn-Cys-S] (CYIQNC) - a disulfide-linked fragment of a neurohypophyseal
      peptide hormone oxytocin (OT) - has been investigated by high-field one
      dimensional (1D) and two-dimensional (2D) NMR spectroscopic methods and compared
      with the results obtained from computer simulation studies. (1)H-NMR results
      based on temperature dependence of amide proton chemical shifts and nuclear
      Overhauser effect indicate that peptide in solution populates different
      conformations, characterized by two fused beta-turns. The segment Ile(3)-Gln(4)
      Asn(5)-Cys(6) yields a preferred type-III beta-turn at residues 4, 5 (HB, 3HN ->
      6CO), while the segment Cys(6), Cys(1)-Tyr(2)-Ile(3) exhibits inherently weaker,
      flexible beta-turn either of type I/II'/III/half-turn at residues 1, 2 (HB, 6HN 
      > 3CO). The computer simulation studies using a mixed protocol of distance
      geometry-simulated annealing followed by constrained minimization, restrained
      molecular dynamics, and energy minimization showed the possibility of existence
      of additional conformations with the hydrogen bonds, (a) 5HN -> 3CO and (b) 2HN 
      > 6CO. These results, therefore, indicate that the additional conformations
      obtained from both NMR and simulation studies can also be possible to the
      peptide. These additional conformations might have very small population in the
      solution and did not show their signatures in these conditions. These findings
      will be helpful in designing more analogs with modifications in the cyclic moiety
      of OT. 

PMID- 25375825
TI  - Evaluating eye fixation and color contrast effects in the measurement of visual
      lobe sizes: comment on Tsang, et al. (2013).
AB  - The visual lobe refers to the useful field of view, functional visual field, or
      conspicuity area in single eye fixation, and the visual lobe size is determined
      by the conspicuity of target presented amongst background characters. This
      comment discusses a study by Tsang, Chan, and Yu (2013) that investigated the
      effect of color contrast on the visual lobe. First, this comment suggests a way
      to improve the precision of their method for measuring a visual lobe. Measuring
      positions of the participants' eyes during visual search with an eye tracker
      would allow checking the eyes' fixation on the center of the search field,
      improving the precision of visual lobe measurement. This comment also suggests a
      more optimal experimental design to investigate the effect of color contrast on
      visual lobe size. Tsang, et al. used colors for target and background that had
      similar contrast (i.e., differences in chromaticity) for the experiments. If the
      color-contrast ratio in each experiment condition had differed enough, the color
      contrast effect on the visual lobe could have been investigated more effectively.

PMID- 25375826
TI  - Altered visual sensory fusion in children with reading difficulties.
AB  - Reading is a multi-sensory and multi-cognitive task, and its difficulties (e.g.,
      dyslexia) are not a unitary disorder. There are probably a variety of
      manifestations that relate to the actual site of impairment. A randomized, pre
      test/post-test nonequivalent-groups design was conducted over 4 months with three
      groups aged between 6 and 8 years. One group comprised 76 participants (34 boys,
      42 girls) with reading difficulties and altered sensory fusion (RD+ASF), a second
      group was made up of 123 students (59 boys, 64 girls) with reading difficulties
      but without altered sensory fusion (RD), and a third group comprised 81
      participants (39 boys, 42 girls) who were young readers (RL) without reading
      delay, paired with the RD group on reading level. The experimental groups
      received intervention in the skills of control, stimulus recognition, and
      phonological awareness during a 4-month period. Both pre-test and post-test
      measures of errors in reading mechanics and reading routes (word and pseudo-word)
      were obtained. Poorer results in mechanics and reading routes of the RD+ASF group
      suggest that the effectiveness of the intervention depended on the
      characteristics of the groups and on the presence of sensory fusion deficits in
      the RD students.

PMID- 25375827
TI  - Lower-right and upper-left biases within upper and lower visual fields in a
      circular array task.
AB  - Visuospatial performance varies along the horizontal and vertical dimensions,
      resulting in behavioral biases such as pseudoneglect. The interaction between the
      horizontal and vertical attentional biases was investigated using a novel
      circular array task capable of conveying relative brightness information across
      vertical and horizontal dimensions simultaneously. In a novel circular array task
      comprised of six discs, the grayscale gradient was disrupted by switching two
      grayscale values within the array. Leftward biases were observed in the lower
      visual fields and rightward biases in the upper visual fields. More importantly,
      the magnitude of bias within the upper/lower horizontal dimension altered
      depending on the relative position of the stimuli along horizontal and vertical
      axes within each dimension. Manipulating the upper-most and leftward discs yield
      stronger biases than manipulating rightward discs. Furthermore, stronger biases
      were observed during bottom and rightward disc manipulation. The upper-left and
      lower-right biases within the horizontal dimension indicate that the interactions
      between the horizontal and vertical biases may not rely simply on the dichotomy
      within the horizontal and vertical dimensions, but also on the relative spatial
      distribution of stimuli within these dimensions.

PMID- 25375828
TI  - Effect of the recreational life review program on patients with dementia in an
      outpatient clinic: a preliminary study.
AB  - The purpose of this study is to investigate the effect of the Life Review Program
      Taiwan (LRP-TW) on outpatients with mild to moderate dementia. Ten individuals
      were selected through purposive sampling and tested using a single group pretest
      posttest design. The Mini-Mental State Examination (MMSE), the Loewenstein
      Occupational Therapy Cognitive Assessment-Geriatric (LOTCA-G) and the Geriatric
      Depression Scale-Short Form (GDS-SF) were used as outcome measures. The total
      scores and three subtests of the LOTCA-G revealed significant differences after
      the intervention. Affective function remained stable through the experiment. The
      LRP-TW may offer a clinical intervention program for supporting cognitive and
      mental performance in individuals with dementia.

PMID- 25375829
TI  - Quantifying colocalization: thresholding, void voxels and the H(coef).
AB  - A critical step in the analysis of images is identifying the area of interest
      e.g. nuclei. When the nuclei are brighter than the remainder of the image an
      intensity can be chosen to identify the nuclei. Intensity thresholding is
      complicated by variations in the intensity of individual nuclei and their
      intensity relative to their surroundings. To compensate thresholds can be based
      on local rather than global intensities. By testing local thresholding methods we
      found that the local mean performed poorly while the Phansalkar method and a new
      method based on identifying the local background were superior. A new
      colocalization coefficient, the H(coef), highlights a number of controversial
      issues. (i) Are molecular interactions measurable (ii) whether to include voxels
      without fluorophores in calculations, and (iii) the meaning of negative
      correlations. Negative correlations can arise biologically (a) because the two
      fluorophores are in different places or (b) when high intensities of one
      fluorophore coincide with low intensities of a second. The cases are distinct and
      we argue that it is only relevant to measure correlation using pixels that
      contain both fluorophores and, when the fluorophores are in different places, to
      just report the lack of co-occurrence and omit these uninformative negative
      correlation. The H(coef) could report molecular interactions in a homogenous
      medium. But biology is not homogenous and distributions also reflect physico
      chemical properties, targeted delivery and retention. The H(coef) actually
      measures a mix of correlation and co-occurrence, which makes its interpretation
      problematic and in the absence of a convincing demonstration we advise caution,
      favouring separate measurements of correlation and of co-occurrence.

PMID- 25375830
TI  - Reviewing the literature for epidemiological trends of dengue disease:
      introduction to a series of seven national systematic literature reviews.

PMID- 25375831
TI  - Graphene oxide amplified fluorescence anisotropy for label-free detection of
      potassium ion.
AB  - Fluorescence anisotropy (FA) has attracted considerable attention, but it has
      been rarely applied for the detection of small molecules and metal ions because
      they are too small to induce evident FA changes. Although some mass amplifying
      strategies have been developed, the recognition probes need to be covalently
      modified with the fluorescent dyes, which is complex and expensive. To overcome
      this limitation, a new simple, label-free and cost-effective method for the
      sensitive detection of potassium ion (K(+)), by using graphene oxide (GO) as FA
      enhancer, a G-rich single stranded DNA (ssDNA) as recognition probe and acridine
      orange (AO) as FA reporting fluorophore, was established in this paper. In the
      absence of K(+), both ssDNA and AO are adsorbed on the surface of GO, and the FA
      of AO is enhanced greatly because the rotation of AO is coupled with the entire
      formation. After the addition of K(+), the ssDNA self-associates into the G
      quadruplex structure. Then, AO can bind with the formed G-quadruplex strongly,
      keeping away from the surface of GO, and the FA of AO decreases significantly
      because of the relatively small size of the complex of AO and G-quadruplex. Thus
      K(+) can be detected sensitively in the range of 10 MUM-2 mM based on the
      evidently decreased FA. This method is a further improvement of the previous
      reported mass amplifying strategies because it does not require any covalent
      labelling of the recognition probe, and it can be potentially applied for
      detection of a variety of other targets. 

PMID- 25375832
TI  - Asymmetric alkynylation of seven-membered cyclic imines by combining chiral
      phosphoric acids and Ag(I) catalysts: synthesis of 11-substituted-10,11
      dihydrodibenzo[b,f][1,4]oxazepine derivatives.
AB  - Asymmetric alkynylation of seven-membered cyclic imine
      dibenzo[b,f][1,4]oxazepines is successfully achieved by combining chiral
      phosphoric acid and Ag(I) catalysts. Various arylacetylenes, conjugated enynes,
      and terminal 1,3-diynes are good substrates for this reaction, and aliphatic
      hexyne is also a suitable donor at elevated temperature. Optimization of this
      approach has provided a facile method to synthesize optically active 11
      substituted-10,11-dihydrodibenzo[b,f][1,4]oxazepine derivatives containing a
      carbon-carbon triple bond with 63-99% ee. Subsequent transformations of the
      carbon-carbon triple bond for the heterocyclic products have been disclosed. 

PMID- 25375833
TI  - Distinct properties of the two isoforms of CDP-diacylglycerol synthase.
AB  - CDP-diacylglycerol synthases (CDS) are critical enzymes that catalyze the
      formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid (PA). Here we
      show in vitro that the two isoforms of human CDS, CDS1 and CDS2, show different
      acyl chain specificities for its lipid substrate. CDS2 is selective for the acyl
      chains at the sn-1 and sn-2 positions, the most preferred species being 1
      stearoyl-2-arachidonoyl-sn-phosphatidic acid. CDS1, conversely, shows no
      particular substrate specificity, displaying similar activities for almost all
      substrates tested. Additionally, we show that inhibition of CDS2 by
      phosphatidylinositol is also acyl chain-dependent, with the strongest inhibition
      seen with the 1-stearoyl-2-arachidonoyl species. CDS1 shows no acyl chain
      dependent inhibition. Both CDS1 and CDS2 are inhibited by their anionic
      phospholipid end products, with phosphatidylinositol-(4,5)-bisphosphate showing
      the strongest inhibition. Our results indicate that CDS1 and CDS2 could create
      different CDP-DAG pools that may serve to enrich different phospholipid species
      with specific acyl chains. 

PMID- 25375834
TI  - Exploration of the zinc finger motif in controlling activity of matrix
      metalloproteinases.
AB  - Discovering ways to control the activity of matrix metalloproteinases (MMPs),
      zinc-dependent enzymes capable of degrading extracellular matrix proteins, is an
      important field of cancer research. We report here a novel strategy for
      assembling MMP inhibitors on the basis of oligopeptide ligands by exploring the
      pattern known as the zinc finger motif. Advanced molecular modeling tools were
      used to characterize the structural binding motifs of experimentally tested MMP
      inhibitors, as well as those of newly proposed peptidomimetics, in their zinc
      containing active sites. The results of simulations based on the quantum
      mechanics/molecular mechanics (QM/MM) approach and Car-Parrinello molecular
      dynamics with QM/MM potentials demonstrate that, upon binding of Regasepin1, a
      known MMP-9 inhibitor, the Zn(2+)(His3) structural element is rearranged to the
      Zn(2+)(Cys2His2) zinc finger motif, in which two Cys residues are borrowed from
      the ligand. Following consideration of the crystal structure of MMP-2 with its
      inhibitor, the oligopeptide APP-IP, we proposed a new peptidomimetic with two
      replacements in the substrate, Tyr3Cys and Asp6Cys. Simulations show that this
      peptide variant blocks an enzyme active site by the Zn(2+)(Cys2His2) zinc finger
      construct. Similarly, a natural substrate of MMP-2, Ace-Gln-Gly ~ Ile-Ala-Gly
      Nme, can be converted to an inhibiting compound by two replacements, Ile by Cys
      and Gly by the d isomer of Cys, favoring formation of the zinc finger motif. 

PMID- 25375835
TI  - Effect of the influenza virus rapid antigen test on a physician's decision to
      prescribe antibiotics and on patient length of stay in the emergency department.
AB  - BACKGROUND: Influenza virus infection is a common reason for visits to the
      emergency department (ED) during the influenza season. A rapid and accurate
      diagnosis of influenza virus infection is important to reduce unnecessary
      antibiotic prescription and to improve patient care. The aim of this study was to
      examine whether using the Influenza Virus Rapid Antigen Test (IVRAT) in the ED
      affects the decision to prescribe antibiotics or the length of hospital stay
      (LOS). METHODS: Data from patients suffering from an influenza-like illness (ILI)
      and who were discharged after visiting the ED at Chungbuk National University
      Hospital were reviewed over two influenza seasons: 2010-2011, when IVRAT was not
      used in the ED, and 2011-2012, when it was. The numbers of antibiotic
      prescriptions issued and the ED LOS during these two seasons were then compared.
      RESULTS: The number of antibiotic prescriptions was significantly lower in 2011
      2012 (54/216, 25.0%) than in 2010-2011 (97/221, 43.9%; P<0.01). However, the
      median ED LOS for patients in 2011-2012 was much longer than that of patients in
      2010-2011 (213 minutes vs. 257 minutes; P<0.01). During the 2011-2012 influenza
      season, 73 ILI patients showed a positive IVRAT result whereas 123 showed a
      negative result. Upon discharge, antibiotics were given to 42/123 (34.1%) ILI
      patients with a negative IVRAT result, but to only 7/73 (9.6%) patients with a
      positive IVRAT result (P<0.01). CONCLUSIONS: Performing IVRAT in the ED reduced
      the prescription of antibiotics to ILI patients discharged after ED care.
      However, the ED LOS for patients who underwent IVRAT was longer than that for
      patients who did not. Thus, performing IVRAT in the ED reduces the unnecessary
      prescription of antibiotics to ILI patients during the influenza season.

PMID- 25375836
TI  - Escitalopram treatment for depressive disorder following acute coronary syndrome:
      a 24-week double-blind, placebo-controlled trial.
AB  - OBJECTIVE: Depression is common after acute coronary syndrome (ACS) and has
      adverse effects on prognosis. There are few evidence-based interventions for
      treating depression in ACS. This study investigated the efficacy and safety of
      escitalopram in treating depressive disorders identified 2-14 weeks after a
      confirmed ACS episode. METHOD: A total of 217 patients with DSM-IV depressive
      disorders (121 major and 96 minor) and ACS were randomly assigned to receive
      escitalopram in flexible doses of 5-20 mg/d (n = 108) or placebo (n = 109) for 24
      weeks. The study was conducted from 2007 to 2013. The primary outcome measure was
      the Hamilton Depression Rating Scale (HDRS). Secondary outcome measures included
      the Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory
      (BDI), Clinical Global Impressions-Severity of Illness scale (CGI-S), Social and
      Occupational Functioning Assessment Scale (SOFAS), and World Health Organization
      Disability Assessment Schedule-12. Cardiovascular safety outcomes included
      echocardiography, electrocardiography, laboratory test, body weight, and blood
      pressure results. RESULTS: Escitalopram was superior to placebo in reducing HDRS
      scores (mean difference = 2.3, P = .016, effect size = 0.38). Escitalopram was
      also superior to placebo in decreasing depressive symptoms evaluated by the
      MADRS, BDI, and CGI-S and in improving SOFAS functioning level. Escitalopram was
      not associated with any harmful changes in cardiovascular safety measures.
      Dizziness was significantly more frequently reported in the escitalopram group (P
      = .018), but there were no significant differences in any other adverse events.
      CONCLUSIONS: These results indicate that escitalopram has clinically meaningful
      antidepressant effects with no evidence of reduced cardiovascular safety in
      depressive disorder following ACS. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT00419471.

PMID- 25375838
TI  - Chemical and computational methods for the characterization of covalent reactive
      groups for the prospective design of irreversible inhibitors.
AB  - Interest in drugs that covalently modify their target is driven by the desire for
      enhanced efficacy that can result from the silencing of enzymatic activity until
      protein resynthesis can occur, along with the potential for increased selectivity
      by targeting uniquely positioned nucleophilic residues in the protein. However,
      covalent approaches carry additional risk for toxicities or hypersensitivity
      reactions that can result from covalent modification of unintended targets. Here
      we describe methods for measuring the reactivity of covalent reactive groups
      (CRGs) with a biologically relevant nucleophile, glutathione (GSH), along with
      kinetic data for a broad array of electrophiles. We also describe a computational
      method for predicting electrophilic reactivity, which taken together can be
      applied to the prospective design of thiol-reactive covalent inhibitors. 

PMID- 25375837
TI  - Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection is the second most
      important cause of death in the first year of life, and early RSV infections are
      associated with the development of asthma. Breastfeeding and serum IgG have been
      shown to protect against RSV infection. Yet, many infants depend on bovine milk
      based nutrition, which at present lacks intact immunoglobulins. OBJECTIVE: To
      investigate whether IgG purified from bovine milk (bIgG) can modulate immune
      responses against human RSV. METHODS: ELISAs were performed to analyse binding of
      bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess
      dose-dependent binding of bIgG to human Fcgamma receptors (FcgammaR) or bIgG
      mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV
      were used to test bIgG-mediated binding and internalisation of pathogens by
      myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells
      by hRSV was evaluated. RESULTS: bIgG recognised human RSV, influenza
      haemagglutinin and Haemophilus influenza. bIgG bound to FcgammaRII on
      neutrophils, monocytes and macrophages, but not to FcgammaRI and FcgammaRIII, and
      could bind simultaneously to hRSV and human FcgammaRII on neutrophils. In
      addition, human neutrophils and dendritic cells internalised pathogens that were
      opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV.
      CONCLUSIONS: The data presented here show that bIgG binds to hRSV and other human
      respiratory pathogens and induces effector functions through binding to human
      FcgammaRII on phagocytes. Thus bovine IgG may contribute to immune protection
      against RSV.

PMID- 25375839
TI  - Synthesis, characterization and biomolecule-binding properties of novel tetra
      platinum(II)-thiopyridylporphyrins.
AB  - The new complexes tetra-platinum(II)-thiopyridylporphyrin 3 and tetra
      platinum(II)-thiopyridylporphyrinato Zn(II) 4 were obtained by coordination of
      the peripheral thiopyridyl units of the free-base 5,10,15,20-tetrakis[2,3,5,6
      tetrafluoro-4-(4-pyridylsulfanyl)phenyl]porphyrin 1 or their corresponding zinc
      complex 2, respectively, with four chloro(2,2'-bipyridine)platinum(II)
      [Pt(bpy)Cl](+) units. Both compounds were characterized by several spectroscopic
      techniques demonstrating a particular behaviour in the emission spectra due to
      the absence or presence of zinc. The tetra-platinum(II)-thiopyridylporphyrins
      exhibited an increase in the emission quantum yield when compared with the
      starting thiopyridylporphyrins 1 and 2. Spectroscopic studies of both platinum
      derivatives reveal their ability to interact unequivocally with DNA from calf
      thymus and DNA of low molecular weight from salmon sperms, and also with the most
      abundant protein in human blood plasma, human serum albumin (HSA). Herein, both
      tetra-platinum(II)-thiopyridylporphyrins 3 and 4 exhibit electrostatic surface
      binding with the negative phosphate groups of DNA. Similar to cationic-anionic
      binding with DNA, tetra-platinum(II)-thiopyridylporphyrinato zinc(II)
      demonstrates a particular binding intercalation mode with DNA. Photophysical
      studies demonstrated that both porphyrins are photostable and able to generate
      singlet oxygen ((1)O2) after light irradiation. Exposure of pMT123 plasmid DNA to
      tetra-platinum(II)-thiopyridylporphyrins and irradiation with light lead to
      single-strand breakage as determined by the conversion of the supercoiled form of
      the plasmid (form I) into the nicked circular form (form II). The tetra
      platinum(II)-thiopyridylporphyrinato Zn(II) demonstrates a particular
      intercalation binding mode with DNA and an ability to cleave DNA after photo
      excitation.

PMID- 25375840
TI  - Breast milk fat content of mothers to small-for-gestational-age infants.
AB  - OBJECTIVE: Little is known about the composition of human milk (HM) expressed by
      mothers of asymmetrically growth-restricted infants. To test the null hypothesis
      that lactating mothers of small-for-gestational-age (SGA) infants produce milk
      with fat content similar to that of lactating mothers of infants whose growth is
      appropriate for gestational age (AGA). STUDY DESIGN: Fifty-six lactating mothers
      of newborns (26 SGA and 30 AGA) were recruited within the first 3 days of
      delivery. Creamatocrit (CMT) levels in HM were measured at 72 h, 7 days and 14
      days postdelivery in capillary tubes after centrifugation at 9000 r.p.m. for 5
      min. RESULT: The groups did not differ in terms of maternal age, body mass index,
      gestational age (GA), pregnancy weight gain and parity. They differed
      significantly in terms of infant's birth weight by design. The mean CMT levels at
      the three time points were similar for the two groups. This remained true when
      timing of the sample (colostrum, transitional, mature milk) was introduced as a
      confounder in the analysis of variance (general linear model). CONCLUSION: Fat
      content of HM is not affected by fetal growth status. We suggest that mothers of
      SGA infants may be reassured that their milk contains adequate amount of fat that
      is appropriate for the growth of their infants.

PMID- 25375841
TI  - Association between tissue characteristics of coronary plaque and distal
      embolization after coronary intervention in acute coronary syndrome patients:
      insights from a meta-analysis of virtual histology-intravascular ultrasound
      studies.
AB  - BACKGROUND AND OBJECTIVES: The predictive value of plaque characteristics
      assessed by virtual histology-intravascular ultrasound (VH-IVUS) including
      fibrous tissue (FT), fibrofatty (FF), necrotic core (NC) and dense calcium (DC)
      in identifying distal embolization after percutaneous coronary intervention (PCI)
      is still controversial. We performed a systematic review and meta-analysis to
      summarize the association of pre-PCI plaque composition and post-PCI distal
      embolization in acute coronary syndrome patients. METHODS: Studies were
      identified in PubMed, OVID, EMBASE, the Cochrane Library, the Current Controlled
      Trials Register, reviews, and reference lists of relevant articles. A meta
      analysis using both fixed and random effects models with assessment of study
      heterogeneity and publication bias was performed. RESULTS: Of the 388 articles
      screened, 10 studies with a total of 872 subjects (199 with distal embolization
      and 673 with normal flow) met the eligibility of our study. Compared with normal
      flow groups, significant higher absolute volume of NC [weighted mean differences
      (WMD): 5.79 mm3, 95% CI: 3.02 to 8.55 mm3; p<0.001] and DC (WMD: 2.55 mm3, 95%
      CI: 0.22 to 4.88 mm3; p = 0.03) were found in acute coronary syndrome patients
      with distal embolization. Further subgroup analysis demonstrated that the
      predictive value of tissue characteristics in determining distal embolization was
      correlated to clinical scenario of the patients, definition of distal
      embolization, and whether the percutaneous aspiration thrombectomy was applied.
      CONCLUSION: Our study that pooled current evidence showed that plaque components
      were closely related to the distal embolization after PCI, especially the
      absolute volume of NC and DC, supporting further studies with larger sample size
      and high-methodological quality.

PMID- 25375842
TI  - The effect of testing distance on intraocular lens power calculation.

PMID- 25375843
TI  - The mystery of collagen cross-linking when it comes to in vivo biomechanical
      measurements.

PMID- 25375844
TI  - Contact lens-assisted collagen cross-linking: is it the working solution?

PMID- 25375845
TI  - The use of femtosecond lasers in cataract surgery: review of the published
      results with the LenSx system.
AB  - PURPOSE: To review the published literature describing the use of the LenSx
      femtosecond laser technology (Alcon Laboratories, Inc., Fort Worth, TX) in
      cataract surgery. METHODS: Literature review. RESULTS: The LenSx system has been
      used in more than 200,000 cataract surgery procedures to date. Pre-clinical
      evaluations have shown that this system produces accurate and reproducible
      capsulorhexes, and that both the energy required for phacoemulsification and
      total phacoemulsification time are less than with conventional
      phacoemulsification. In comparative studies, femtosecond lasers have been shown
      to produce more precise and reproducible capsulorhexes than manual procedures,
      and better intraocular lens placement; capsule overlap, circularity of
      capsulotomy, and centration of the intraocular lens are consistently better with
      femtosecond lasers than with manual procedures. The improved quality of
      capsulorhexis and intraocular lens positioning are reflected in favorable visual
      and refractive outcomes. As with any new technology, there is a significant
      learning curve: prospective cohort studies have shown that the incidence of
      intraoperative complications such as suction breaks or anterior capsular tears or
      tags decreases with experience. In general, the incidence of such complications
      is within the range (< 2%) considered in recent evidence-based guidelines to be
      feasible and desirable. CONCLUSIONS: Although femtosecond laser cataract surgery
      is in its infancy, the technology is evolving rapidly and offers the potential
      for more consistent and predictable results after cataract surgery.

PMID- 25375846
TI  - Laser-assisted mini-capsulotomy: a new technique for intumescent white cataracts.
AB  - PURPOSE: To describe a new two-step femtosecond laser-assisted technique for
      intumescent white cataracts. METHODS: In 6 eyes with intumescent white cataracts,
      a laser-assisted mini-capsulotomy was performed first to release the
      intralenticular pressure. In the next step, the fluid milky lens material was
      removed from the anterior chamber before the eyes were re-docked to the laser
      system and a second larger anterior capsulotomy (4.5-mm diameter) was performed.
      Finally, the cataractous lens material was removed followed by intraocular lens
      implantation in the capsular bag. RESULTS: In all cases, the laser system was
      able to identify and cut the anterior capsule without complications. Small
      residual tissue bridges were recognized after laser-assisted mini-capsulotomy in
      2 eyes and solved with the dimple-down maneuver. The second, larger capsulotomy
      demonstrated satisfactory quality and a 360 degrees  overlap on the intraocular
      lens' optic was achieved in all cases. CONCLUSIONS: This novel technique for
      intumescent white cataracts using a two-step laser-assisted mini-capsulotomy has
      the potential to avoid complications.

PMID- 25375847
TI  - Transepithelial iontophoresis corneal collagen cross-linking for progressive
      keratoconus: initial clinical outcomes.
AB  - PURPOSE: To report initial clinical results of transepithelial corneal collagen
      cross-linking with iontophoresis (I-CXL). METHODS: Twenty eyes of 20 patients
      diagnosed as having progressive keratoconus who underwent I-CXL were included in
      this prospective non-randomized clinical study. Corrected distance visual acuity
      (CDVA), spherical equivalent and cylinder refraction, various corneal topography
      and Scheimpflug tomography parameters, aberrometry, anterior segment optical
      coherence tomography, and endothelial cell count were assessed at baseline and at
      1, 3, 6, and 12 months postoperatively. RESULTS: CDVA improved significantly at
      3, 6, and 12 months postoperatively (logMAR difference of -0.07 +/- 0.01, -0.09
      +/- 0.03, and -0.12 +/- 0.06, respectively; P < .05). Aberrometry remained stable
      during follow-up and a trend toward improvement was noted. All topographic
      parameters (including maximum keratometry) were stable during the follow-up, but
      exhibited a positive non-significant trend toward improvement. Minimum corneal
      thickness values were stable for up to 12 months postoperatively. None of the
      patients showed a progression of keratoconus. Endothelial cell counts did not
      change significantly (P > .05). CONCLUSIONS: Preliminary results up to 1 year
      postoperatively indicate the efficacy of I-CXL in stabilizing the progression of
      this degenerative disease combined with significant improvement of CDVA. I-CXL,
      which spares the corneal epithelium, has the potential to become a valid
      alternative for halting the progression of keratoconus while reducing
      postoperative patient pain, risk of infection, and treatment time in select
      patients; however, the relative efficacy of this technique compared to standard
      epithelium-off techniques remains to be determined.

PMID- 25375848
TI  - Comparison of two multifocal intraocular lens designs that differ only in near
      add.
AB  - PURPOSE: To evaluate monocular functional outcomes after the implantation of the
      AcrySof ReSTOR SN6AD2 intraocular lens (IOL) (+2.5 diopters [D] near add) (Alcon
      Laboratories, Inc., Fort Worth, TX) and the AcrySof ReSTOR SN6AD1 IOL (+3.0 D
      near add) (Alcon Laboratories, Inc.). METHODS: This prospective, comparative,
      nonrandomized single-blind observational study comprised 62 eyes of 62 patients
      that underwent phacoemulsification and implantation of a multifocal IOL: SN6AD2
      (31 eyes) (+2.5 group) and SN6AD1 (31 eyes) (+3.0 group). Twelve months after
      surgery, monocular near (30 and 40 cm), intermediate (50, 60, and 70 cm), and
      distance (4 m) visual acuity were evaluated with the internal root mean square
      and modulation transfer function. Both parameters were evaluated at the 4- and 6
      mm pupil sizes. RESULTS: No statistical differences at 4 m were found between the
      groups. The +2.5 group obtained better performances at all intermediate distances
      (50 cm, 0.23 +/- 0.14 vs 0.32 +/- 0.13; 60 and 70 cm, 0.21 +/- 0.10 vs 0.41 +/-
      0.14 and 0.24 +/- 0.10 vs 0.53 +/- 0.17, respectively), whereas the near visual
      acuity was better for the +3.0 group (30 and 40 cm, 0.36 +/- 0.18 vs 0.14 +/-
      0.09 and 0.36 +/- 0.19 vs 0.17 +/- 0.07, respectively). The root mean square was
      lower for the +2.5 group compared to the +3.0 group, whereas the modulation
      transfer function showed overlapping results between the two models. CONCLUSIONS:
      Both IOL models showed good results in distance vision; the +2.5 D IOL seemed to
      provide better intermediate vision than the +3.0 D IOL. For near vision, the +3.0
      D model performed better than the +2.5 D model.

PMID- 25375849
TI  - Clinical outcomes with a trifocal intraocular lens: a multicenter study.
AB  - PURPOSE: To evaluate the clinical results and safety obtained with a new type of
      multifocal intraocular lens (IOL) using a trifocal design to achieve
      pseudoaccommodation. METHODS: A pilot observational study of patients with a
      trifocal IOL (FineVision; PhysIOL, Liege, Belgium) implanted by 1 of 12 surgeons
      between March and December 2010. Visual outcomes that were assessed
      postoperatively included uncorrected and corrected distance, intermediate, and
      near visual acuity. RESULTS: One hundred ninety-eight eyes of 99 patients were
      analyzed. Patients were observed for an average of 6.44 +/- 4.67 months (range:
      0.2 to 17 months). Preoperative corrected distance visual acuity was 0.22 +/-
      0.26 logMAR. At the final follow-up visit, corrected distance visual acuity was
      0.01 +/- 0.10 logMAR, uncorrected distance visual acuity was 0.01 +/- 0.06
      logMAR, uncorrected intermediate visual acuity was 0.08 +/- 0.10 logMAR, and mean
      uncorrected near visual acuity was 0.00 +/- 0.04 logMAR. Postoperative binocular
      uncorrected distance visual acuity was 0.01 +/- 0.07 logMAR, uncorrected
      intermediate visual acuity was 0.06 +/- 0.08 logMAR, and uncorrected near visual
      acuity was -0.03 +/- 0.04 logMAR. Postopeative mean residual sphere was 0.21 +/-
      0.48 diopters (D), with a residual cylinder of -0.24 +/- 0.31 D. Postoperative
      spherical equivalent was 0.11 +/- 0.36 D. CONCLUSIONS: The results demonstrated
      that the trifocal FineVision IOL is able to restore near, intermediate, and
      distance visual function.

PMID- 25375850
TI  - Initial experience with a new refractive rotationally asymmetric multifocal
      intraocular lens.
AB  - PURPOSE: To assess efficacy, safety, predictability, and patient satisfaction
      after refractive lens exchange with a new refractive rotational asymmetric
      multifocal intraocular lens. METHODS: One hundred six eyes of 53 patients after
      bilateral refractive lens exchange with the SBL-3 lens (Lenstec, Inc., Christ
      Church, Barbados) implantation were evaluated. The mean preoperative refractive
      sphere was +1.06 +/- 2.63 diopters (D) (range: -8.25 to +5.00 D) and the mean
      refractive cylinder was -0.51 +/- 0.46 D (range: -2.00 to 0.00 D). Monocular and
      binocular uncorrected and corrected distance visual acuity, uncorrected and
      distance-corrected intermediate visual acuity, uncorrected and distance-corrected
      near visual acuity, defocus curve, and patient satisfaction were evaluated 3
      months postoperatively. RESULTS: At 3 months, 84.9% (90 eyes) were within +/-0.50
      D of emmetropia. The mean postoperative uncorrected distance visual acuity was 
      0.03 +/- 0.09 logMAR (6/6 Snellen) monocularly and -0.08 +/- 0.08 logMAR (6/4.8
      Snellen) binocularly. The mean monocular and binocular uncorrected near visual
      acuity were 0.12 +/- 0.12 and 0.08 +/- 0.10 logMAR (6/7.5 Snellen), respectively.
      Defocus curve showed a slight drop off for vergences equivalent to intermediate
      vision. Although some night vision phenomena were reported, overall satisfaction
      was high. No intraoperative or postoperative complications occurred in this
      study. CONCLUSIONS: The new refractive rotationally asymmetric intraocular lens
      provided good range of vision for near, intermediate, and distance. Long-term
      follow-ups are necessary to evaluate the performance of this intraocular lens.

PMID- 25375851
TI  - Comparative evaluation of higher-order aberrations and corneal asphericity
      between wavefront-guided and aspheric LASIK for myopia.
AB  - PURPOSE: To compare visual outcome, higher-order aberrations, and corneal
      asphericity (Q value) between wavefront-guided and aspheric LASIK for myopia and
      myopic astigmatism. METHODS: Forty patients were randomly selected to receive
      wavefront-guided LASIK (wavefront-guided group) or aspheric LASIK (aspheric
      group) (40 eyes of 20 patients in each group) using the Technolas 217z excimer
      laser platform (Bausch & Lomb, Rochester, NY). Flaps were created using the
      Zyoptix XP microkeratome (Bausch & Lomb). Preoperative and postoperative
      evaluation included uncorrected distance visual acuity (UDVA), corneal
      topography, wavefront aberrometry, and contrast sensitivity. Minimum follow-up
      period was 6 months. RESULTS: At 6 months postoperatively, the aspheric group had
      significantly better UDVA (logMAR 0.04 +/- 0.04 [Snellen 20/16] [range: -0.079 to
      0.000]) and lower mean residual spherical error (+0.10 +/- 0.52 diopters [D]
      [range: -1.12 to 1.25 D]) than the wavefront-guided group (logMAR UDVA 0.00 +/-
      0.07 [range: -0.079 to 0.176]; MRSE -0.35 +/- 0.47 D [range: -1.5 to 0.62 D]) (P
      = .003 and < .001, respectively). Mean change in higher-order aberration root
      mean square at 6 months postoperatively (6-mm pupil) was 0.16 +/- 0.17 um after
      aspheric LASIK and 0.27 +/- 0.28 um after wavefront-guided LASIK (P = .02).
      Aspheric LASIK induced minimal change in spherical aberrations postoperatively
      (0.03 +/- 0.12 um, P = .09), unlike wavefront-guided LASIK (0.23 +/- 0.17 um, P <
      .01). Change in Q value was significantly less in the aspheric group (0.53 +/-
      0.31) than the wavefront-guided group (0.91 +/- 0.30) (P < .01). The aspheric
      group had significant improvement in contrast sensitivity at all spatial
      frequencies (P < .01), whereas the wavefront-guided group showed a slight
      decrease at higher spatial frequency (18 cycles per degree). CONCLUSIONS:
      Aspheric LASIK induced significantly less change in higher-order aberrations and
      maintained corneal asphericity better than wavefront-guided LASIK. The visual
      outcome and contrast sensitivity was better in the aspheric group at 6 months
      postoperatively.

PMID- 25375853
TI  - Tracheal cartilaginous sleeve association with syndromic midface hypoplasia.
AB  - IMPORTANCE: We report 2 new cases of tracheal cartilaginous sleeve and perform a
      systematic literature review of all documented cases of this condition. We aim to
      increase awareness of this anomaly and provide recommendations for both
      intraoperative and postoperative management of patients with tracheal
      cartilaginous sleeve undergoing tracheostomy. OBSERVATIONS: We studied the
      clinical records of 2 children with tracheal cartilaginous sleeves and short
      tracheas treated at our institution. One of these patients had Beare-Stevenson
      syndrome, and the other had Crouzon syndrome. Both patients required tracheostomy
      for persistent upper airway obstruction, and both required custom-length
      tracheostomy tubes. Bronchoscopy and needle localization were beneficial in
      performing tracheostomy on these patients. All documented cases of tracheal
      cartilaginous sleeve in the literature were found to be associated with midface
      hypoplasia secondary to syndromic craniosynostosis. Seventy-five percent of cases
      required tracheostomy. CONCLUSIONS AND RELEVANCE: Tracheal cartilaginous sleeve
      can be associated with Beare-Stevenson syndrome. In infants with midface
      hypoplasia associated with a craniosynostosis syndrome undergoing tracheostomy,
      the surgeon must be prepared to encounter and manage tracheal cartilaginous
      sleeve intraoperatively. Bronchoscopy and needle localization can be beneficial
      when performing tracheostomy in these patients. Customized, shorter-length
      tracheostomy tubes should be considered for these patients.

PMID- 25375852
TI  - Transcriptomic changes triggered by hypoxia: evidence for HIF-1alpha-independent,
      [Na+]i/[K+]i-mediated, excitation-transcription coupling.
AB  - This study examines the relative impact of canonical hypoxia-inducible factor
      1alpha- (HIF-1alpha and Na+i/K+i-mediated signaling on transcriptomic changes
      evoked by hypoxia and glucose deprivation. Incubation of RASMC in ischemic
      conditions resulted in ~3-fold elevation of [Na+]i and 2-fold reduction of [K+]i.
      Using global gene expression profiling we found that Na+,K+-ATPase inhibition by
      ouabain or K+-free medium in rat aortic vascular smooth muscle cells (RASMC) led
      to the differential expression of dozens of genes whose altered expression was
      previously detected in cells subjected to hypoxia and ischemia/reperfusion. For
      further investigations, we selected Cyp1a1, Fos, Atf3, Klf10, Ptgs2, Nr4a1, Per2
      and Hes1, i.e. genes possessing the highest increments of expression under
      sustained Na+,K+-ATPase inhibition and whose implication in the pathogenesis of
      hypoxia was proved in previous studies. In ouabain-treated RASMC, low-Na+, high
      K+ medium abolished amplification of the [Na+]i/[K+]i ratio as well as the
      increased expression of all tested genes. In cells subjected to hypoxia and
      glucose deprivation, dissipation of the transmembrane gradient of Na+ and K+
      completely eliminated increment of Fos, Atf3, Ptgs2 and Per2 mRNAs and sharply
      diminished augmentation expression of Klf10, Edn1, Nr4a1 and Hes1. In contrast to
      low-Na+, high-K+ medium, RASMC transfection with Hif-1a siRNA attenuated
      increments of Vegfa, Edn1, Klf10 and Nr4a1 mRNAs triggered by hypoxia but did not
      impact Fos, Atf3, Ptgs2 and Per2 expression. Thus, our investigation
      demonstrates, for the first time, that Na+i/K+i-mediated, Hif-1alpha- 
      independent excitation-transcription coupling contributes to transcriptomic
      changes evoked in RASMC by hypoxia and glucose deprivation. 

PMID- 25375855
TI  - Comparison of optic disc morphology of optic nerve atrophy between compressive
      optic neuropathy and glaucomatous optic neuropathy.
AB  - OBJECTIVES: To compare the optic nerve head (ONH) structure between compressive
      optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to determine
      whether selected ONH quantitative parameters effectively discriminate between GON
      and CON, especially CON cases presenting with a glaucoma-like disc. METHODS: We
      prospectively assessed 34 patients with CON, 34 age-matched patients with
      moderate or severe GON, and 34 age-matched healthy control subjects. The
      quantitative parameters of ONH structure were compared using the Heidelberg
      Retina Tomograph 2 (HRT2) and Spectralis optical coherence tomography with an
      enhanced depth imaging method. RESULTS: The mean and maximum cup depths of CON
      were significantly smaller than those with GON (P < 0.001 and P < 0.001,
      respectively). The distance between Bruch's membrane opening and anterior surface
      of the lamina cribrosa (BMO-anterior LC) of CON was also significantly smaller
      than that of glaucoma but was similar to that of the healthy group (P < 0.001 and
      P = 0.47, respectively). Based on Moorfields regression analysis of the glaucoma
      classification of HRT2, 15 eyes with CON were classified with a glaucoma-like
      disc. The cup/disc area ratio did not differ between cases of CON with a glaucoma
      like disc and cases of GON (P = 0.16), but the BMO-anterior LC and mean and
      maximum cup depths of CON cases with a glaucoma-like disc were smaller than those
      in GON (P = 0.005, P = 0.003, and P = 0.001, respectively). CONCLUSIONS:
      Measurements of the cup depths and the LC depth had good ability to differentiate
      between CON with a glaucoma-like disc and glaucoma. There was no laminar
      remodeling detected by laminar surface position in the patients with CON compared
      to those with GON.

PMID- 25375856
TI  - Genomic insights into the fungal pathogens of the genus pneumocystis: obligate
      biotrophs of humans and other mammals.

PMID- 25375854
TI  - Iodine deficiency and excess coexist in china and induce thyroid dysfunction and
      disease: a cross-sectional study.
AB  - BACKGROUND: In spite of the salt iodization, iodine deficiency disorders (IDD)
      have not been sustainably eliminated in China. There are coastal areas with low
      iodized salt coverage rates (iodine nutrition is inadequate) and other areas with
      excessive amounts of iodine in the drinking water. OBJECTIVE: This study aimed to
      clarify the association of iodine deficiencies resulting from a low coverage rate
      of iodized salt, excess iodine intake from drinking water with thyroid function
      and disease in adults. DESIGN: A cross-sectional study was conducted in adults in
      different iodine nutrition areas in three provinces in China. RESULTS: The
      prevalence of thyroid nodules was 15.52%, 8.66% and 22.17% in the iodine excess,
      sufficient and deficient groups, respectively. The prevalence of subclinical
      hypothyroidism was 20.09%, 10.41%, and 2.25% in the excess, sufficient and
      deficient iodine groups, respectively. The prevalence of subclinical
      hyperthyroidism and overt hyperthyroidism in the iodine deficient group was
      higher than that in the iodine excess group ([Formula: see text] = 9.302, p =
      0.002) and iodine sufficient group ([Formula: see text] = 7.553, p = 0.006).
      Thyroid-stimulating hormone (TSH) was significantly correlated with excess iodine
      intake (beta = 1.764,P = 0.001) and deficient iodine intake (beta = -1.219, P =
      0.028). CONCLUSIONS: Thyroid nodules are more likely to be present in the iodine
      excess and deficient areas than in the iodine sufficient areas. Subclinical
      hyperthyroidism and overt hyperthyroidism are more likely to be prevalent in the
      iodine deficient areas than in the iodine excess or sufficient areas. Subclinical
      hypothyroidism is more likely to be prevalent in the high iodine intake areas
      than in the iodine deficient or sufficient areas. Median TSH may be deemed as an
      alternative indicator for monitoring the iodine nutrition status of the adult
      population in iodine excess and deficient areas.

PMID- 25375857
TI  - Introduction: Health equity among incarcerated female adolescents and adult
      women: infectious and other disease morbidity.

PMID- 25375859
TI  - Docetaxel inhibits urethral stricture formation, an initial study in rabbit
      model.
AB  - INTRODUCTION: Urethral stricture, a frequent source of lower urinary tract
      disorders in men, is still a difficult problem for urologists. Based the anti
      restenosis effect of paclitaxel on coronary artery, the role of docetaxel, a semi
      synthetic analogue of paclitaxel, in limiting urethral stricture formation was
      studied. METHODS: Forty adult New Zealand male rabbits were involved in this
      study, which were randomly assigned into 3 groups, namely a high dose docetaxel
      (DH, 0.1 mg/d), a low dose docetaxel (DL, 0.01 mg/d) and a control (C) group,
      with 16, 16, 8 rabbits in each group, respectively. All animals underwent a 10 mm
      long circumferential electrocoagulation of the bulbar urethra with a 13Fr
      pediatric resectoscope. Drugs were given by urethral irrigation daily and
      continuous for 28 days. Stricture formation was assessed by retrograde
      urethrography and videourethroscopy. Urethra pathology was evaluated by
      hematoxylin and eosin staining and Sirius red staining. RESULTS: At the end of
      this study, 15, 14 and 7 rabbits remained for evaluation in DH, DL and C group,
      respectively. Urethral diameters in DH, DL and C group were (7.17+/-1.63) mm,
      (6.55+/-0.62) mm, (3.23+/-1.36) mm, with a normal urethral diameter of (9.08+/
      1.29) mm. Lumen reduction in DH, DL and C group were (36.93+/-11.58)%, (48.03+/
      7.89)% and (84.66+/-14.95)%, respectively. Statistically difference could be
      found between every two groups (p<0.05) both in urethral diameters and in lumen
      reduction, except for compare of urethral diameters between DH and DL group.
      Histological examination confirmed mass fibrous tissue and collagen content at
      the stricture sit in C group, whereas less in docetaxel treated rabbits.
      CONCLUSIONS: Docetaxel could limit urethral stricture formation, which may be due
      to inhibition of fibrous tissue and collagen expression. Docetaxel may become a
      new choice in the prevention of urethral stricture formation.

PMID- 25375860
TI  - Effects of sex, age, and fasting conditions on plasma lipidomic profiles of
      fasted Sprague-Dawley rats.
AB  - Circulating lipid molecules reflect biological processes in the body and, thus,
      are useful tools for preclinical estimation of the efficacy and safety of newly
      developed drugs. However, background information on profiles of circulating lipid
      molecules in preclinical animal models is limited. Therefore, we examined the
      effects of multiple factors such as sex (fasted male vs. female), age (fasted 10
      vs. 30 weeks old), and feeding conditions (feeding vs. fasting, 16 vs. 22 hr
      fasting, 10 AM vs. 4 PM blood collection), on the global profiles of lipid
      molecules in plasma from Sprague-Dawley rats by using a lipidomic approach. Our
      assay platform determined 262 lipid molecules (68 phospholipids, 20
      sphingolipids, 138 neutral lipids, and 36 polyunsaturated fatty acids and their
      metabolites) in rat plasma. Multivariate discriminant analysis (orthogonal
      partial least squares discriminant analysis) and heat maps of statistically
      significant lipid molecules revealed that the plasma lipid profiles in rats are
      predominantly influenced by feeding conditions, followed by sex and age. In
      addition, the fasting duration (16 vs. 22 hr fasting) or the time of blood
      collection (10 AM vs. 4 PM blood collection) has limited or no contribution on
      the profiles of lipid molecules in rat plasma. Our results provide useful,
      fundamental information for exploring and validating biomarkers in future
      preclinical studies and may help to establish regulatory standards for such
      studies. 

PMID- 25375863
TI  - A longitudinal study of semantic grouping strategy use in 6-11-year-old children:
      investigating developmental phases, the role of working memory, and strategy
      transfer.
AB  - This two-cohort longitudinal study on the development of the semantic grouping
      strategy had three goals. First, the authors examined if 6-7-year-olds are
      nonstrategic before becoming strategic after prompting at 8-9 years of age, and
      if 8-9-year-olds are prompted strategic before spontaneous strategy use at 10-11
      years of age. Children 6-7 and 8-9 years old performed two sort-recall tasks (one
      without and one with a grouping prompt) at two time points separated 1.5 years
      from each other. Second, the authors investigated whether short-term or working
      memory capacity at time point 1 predicted recall in children who did or did not
      use the semantic grouping strategy 1.5 years later. Third, the authors
      investigated whether prompted strategic children and children who used the
      strategy spontaneously differed in strategy transfer to a new task. Developmental
      results confirmed previous cross-sectional results, but in a longitudinal two
      cohort study 6-7-year-olds were nonstrategic, and became prompted strategic
      around 8-9 years of age, followed by spontaneous strategy use at age 10-11 years.
      The authors found that memory capacity was not predictive of later use of the
      strategy. New findings were that prompted strategic children were as equally able
      as spontaneously strategic children to transfer the strategy to a new task,
      albeit with smaller recall benefits.

PMID- 25375864
TI  - Evaluation of an X-ray-excited optical microscope for chemical imaging of metal
      and other surfaces.
AB  - The application of a modular system for the nondestructive chemical imaging of
      metal and other surfaces is described using heritage metals as an example. The
      custom-built X-ray-excited optical luminescence (XEOL) microscope, XEOM 1, images
      the chemical state and short-range atomic order of the top 200 nm of both
      amorphous and crystalline surfaces. A broad X-ray beam is used to illuminate
      large areas (up to 4 mm(2)) of the sample, and the resulting XEOL emission is
      collected simultaneously for each pixel by a charge-coupled device sensor to form
      an image. The input X-ray energy is incremented across a range typical for the X
      ray absorption near-edge structure (XANES) and an image collected for each
      increment. The use of large-footprint beams combined with parallel detection
      allows the power density to be kept low and facilitates complete nondestructive
      XANES mapping on a reasonable time scale. In this study the microscope was
      evaluated by imaging copper surfaces with well-defined patterns of different
      corrosion products (cuprite Cu2O and nantokite CuCl). The images obtained show
      chemical contrast, and filtering the XEOL light allowed different corrosion
      products to be imaged separately. Absorption spectra extracted from software
      selected regions of interest exhibit characteristic XANES fingerprints for the
      compounds present. Moreover, when the X-ray absorption edge positions were
      extracted from each spectrum, an oxidation state map of the sample could be
      compiled. The results show that this method allows one to obtain nondestructive
      and noninvasive information at the micrometer scale while using full-field
      imaging. 

PMID- 25375862
TI  - Topical application of a platelet activating factor receptor agonist suppresses
      phorbol ester-induced acute and chronic inflammation and has cancer
      chemopreventive activity in mouse skin.
AB  - Platelet activating factor (PAF) has long been associated with acute edema and
      inflammatory responses. PAF acts by binding to a specific G-protein coupled
      receptor (PAF-R, Ptafr). However, the role of chronic PAF-R activation on
      sustained inflammatory responses has been largely ignored. We recently
      demonstrated that mice lacking the PAF-R (Ptafr-/- mice) exhibit increased
      cutaneous tumorigenesis in response to a two-stage chemical carcinogenesis
      protocol. Ptafr-/- mice also exhibited increased chronic inflammation in response
      to phorbol ester application. In this present study, we demonstrate that topical
      application of the non-hydrolysable PAF mimetic (carbamoyl-PAF (CPAF)), exerts a
      potent, dose-dependent, and short-lived edema response in WT mice, but not Ptafr 
      /- mice or mice deficient in c-Kit (c-KitW-sh/W-sh mice). Using an ear
      inflammation model, co-administration of topical CPAF treatment resulted in a
      paradoxical decrease in both acute ear thickness changes associated with a single
      PMA application, as well as the sustained inflammation associated with chronic
      repetitive PMA applications. Moreover, mice treated topically with CPAF also
      exhibited a significant reduction in chemical carcinogenesis. The ability of CPAF
      to suppress acute and chronic inflammatory changes in response to PMA
      application(s) was PAF-R dependent, as CPAF had no effect on basal or PMA-induced
      inflammation in Ptafr-/- mice. Moreover, c-Kit appears to be necessary for the
      anti-inflammatory effects of CPAF, as CPAF had no observable effect in c-KitW
      sh/W-sh mice. These data provide additional evidence that PAF-R activation exerts
      complex immunomodulatory effects in a model of chronic inflammation that is
      relevant to neoplastic development. 

PMID- 25375861
TI  - The role of cis regulatory evolution in maize domestication.
AB  - Gene expression differences between divergent lineages caused by modification of
      cis regulatory elements are thought to be important in evolution. We assayed
      genome-wide cis and trans regulatory differences between maize and its wild
      progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred
      lines for three tissue types (ear, leaf and stem). Pervasive regulatory variation
      was observed with approximately 70% of ~17,000 genes showing evidence of
      regulatory divergence between maize and teosinte. However, many fewer genes
      (1,079 genes) show consistent cis differences with all sampled maize and teosinte
      lines. For ~70% of these 1,079 genes, the cis differences are specific to a
      single tissue. The number of genes with cis regulatory differences is greatest
      for ear tissue, which underwent a drastic transformation in form during
      domestication. As expected from the domestication bottleneck, maize possesses
      less cis regulatory variation than teosinte with this deficit greatest for genes
      showing maize-teosinte cis regulatory divergence, suggesting selection on cis
      regulatory differences during domestication. Consistent with selection on cis
      regulatory elements, genes with cis effects correlated strongly with genes under
      positive selection during maize domestication and improvement, while genes with
      trans regulatory effects did not. We observed a directional bias such that genes
      with cis differences showed higher expression of the maize allele more often than
      the teosinte allele, suggesting domestication favored up-regulation of gene
      expression. Finally, this work documents the cis and trans regulatory changes
      between maize and teosinte in over 17,000 genes for three tissues.

PMID- 25375866
TI  - POLST: resolving ageism issues in New Jersey.

PMID- 25375867
TI  - Announcing the 2014 Edward J. Ill Excellence in Medicine Awards(r).

PMID- 25375865
TI  - Percutaneous dilatational tracheostomy with a double-lumen endotracheal tube: a
      comparison of feasibility, gas exchange, and airway pressures.
AB  - OBJECTIVE: Gas exchange and airway pressures are markedly altered during
      percutaneous dilatational tracheostomy (PDT). A double-lumen endotracheal tube
      (DLET) has been developed for better airway management during PDT. The current
      study prospectively evaluated the in vivo feasibility, gas exchange, and airway
      pressures during PDT with DLET compared with a conventional endotracheal tube
      (ETT). METHODS: According to eligibility criteria, patients were divided into a
      case group (those receiving PDT with DLET) and a control group (those receiving
      PDT with a conventional ETT). The Ciaglia single-dilator technique was used for
      PDT in both groups. The primary end point of this study was the feasibility of
      tracheostomy with DLET. The secondary end points were a comparison of gas
      exchange, airway pressures, minute volume, and tidal volume before, during, and
      after PDT performed with DLET and conventional ETT. RESULTS: Ten patients meeting
      the inclusion criteria were assigned to each group. PDTs were performed without
      difficulties in nine patients in the DLET group and 10 patients in the
      conventional ETT group. During PDT, gas exchange, airway pressures, and minute
      ventilation remained more stable in the DLET group and were significantly
      different from those in the conventional ETT group. CONCLUSIONS: PDT with DLET
      can be performed safely without difficulties limiting the technique. Furthermore,
      during PDT, the use of the DLET resulted in more stable gas exchange, airway
      pressures, and ventilation than PDT with a conventional ETT. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01691222; URL: www.clinicaltrials.gov.

PMID- 25375868
TI  - An interview with Joseph P. Costabile, MD: insights into protecting physician
      autonomy and maintaining standards of care.

PMID- 25375869
TI  - Prevention quality indicators focus improvements on community health.

PMID- 25375870
TI  - Lyme disease in pregnancy: a New Jersey medical advisory.

PMID- 25375871
TI  - Pitfalls of complementary medicine: the challenge of herbal medications and
      nutritional supplements.

PMID- 25375872
TI  - Legislative brief: New Jersey legislative update.

PMID- 25375873
TI  - Patient education: the route to better health.

PMID- 25375874
TI  - IR near-field spectroscopy and imaging of single Li(x)FePO4 microcrystals.
AB  - This study demonstrates the unique capability of infrared near-field nanoscopy
      combined with Fourier transform infrared spectroscopy to map phase distributions
      in microcrystals of Li(x)FePO4, a positive electrode material for Li-ion
      batteries. Ex situ nanoscale IR imaging provides direct evidence for the
      coexistence of LiFePO4 and FePO4 phases in partially delithiated single-crystal
      microparticles. A quantitative three-dimensional tomographic reconstruction of
      the phase distribution within a single microcrystal provides new insights into
      the phase transformation and/or relaxation mechanism, revealing a FePO4 shell
      surrounding a diamond-shaped LiFePO4 inner core, gradually shrinking in size and
      vanishing upon delithiation of the crystal. The observed phase propagation
      pattern supports recent functional models of LiFePO4 operation relating
      electrochemical performance to material design. This work demonstrates the
      remarkable potential of near-field optical techniques for the characterization of
      electrochemical materials and interfaces.

PMID- 25375875
TI  - Axial thiophenolate coordination on diiron(III)bisporphyrin: influence of heme
      heme interactions on structure, function and electrochemical properties of the
      individual heme center.
AB  - The binding of a series of substituted thiophenols as axial ligands on a highly
      flexible ethane-bridged diiron(III)bisporphyrin framework has been investigated
      as a model of diheme proteins. Spectroscopic characterization reveals a high-spin
      (S = 5/2) state of iron for all of the pentacoordinate thiophenolato complexes.
      In the UV-visible spectra of the complexes, the positions of the Soret and band I
      have been found to be dependent on the pKa of thiophenols. The alternating shift
      pattern, which has opposite sign of the chemical shifts for meta- vs. ortho- and
      para-protons in the (1)H NMR spectra, is attributed to negative and positive spin
      densities, respectively, on thiophenolate carbon atoms and is indicative of pi
      spin delocalization to the bound thiophenolate ligand. The Fe(III)/Fe(II) redox
      couple of the complexes bears a linear relationship with the pKa of thiophenol
      and is found to be positively shifted with decreasing pKa. The effect of the
      electronic nature of the substituent on the thiophenolate ring has also been
      demonstrated in which a large potential range of 540 mV was observed (in contrast
      to the value of only 270 mV in case of monoheme analogues) for the Fe(III)/Fe(II)
      redox couple on going from monoheme to diheme and is attributed to the interheme
      interaction. Also, the Fe(III)/Fe(II) redox potential of the thiophenolato
      complexes has been found to be more positively shifted compared to their
      phenolato analogues, which was further supported by DFT calculation. The addition
      of another thiophenol at the sixth axial position of the five-coordinate
      thiophenolato complex causes a change in iron spin from high (S = 5/2) to low (S
      = 1/2) along with a large positive shift of 490 mV for the Fe(III)/Fe(II) redox
      couple.

PMID- 25375877
TI  - Quantitative autofluorescence as a clinical tool for expedited differential
      diagnosis of retinal degeneration.

PMID- 25375876
TI  - 24-hour rhythms of DNA methylation and their relation with rhythms of RNA
      expression in the human dorsolateral prefrontal cortex.
AB  - Circadian rhythms modulate the biology of many human tissues, including brain
      tissues, and are driven by a near 24-hour transcriptional feedback loop. These
      rhythms are paralleled by 24-hour rhythms of large portions of the transcriptome.
      The role of dynamic DNA methylation in influencing these rhythms is uncertain.
      While recent work in Neurospora suggests that dynamic site-specific circadian
      rhythms of DNA methylation may play a role in modulating the fungal molecular
      clock, such rhythms and their relationship to RNA expression have not, to our
      knowledge, been elucidated in mammalian tissues, including human brain tissues.
      We hypothesized that 24-hour rhythms of DNA methylation exist in the human brain,
      and play a role in driving 24-hour rhythms of RNA expression. We analyzed DNA
      methylation levels in post-mortem human dorsolateral prefrontal cortex samples
      from 738 subjects. We assessed for 24-hour rhythmicity of 420,132 DNA methylation
      sites throughout the genome by considering methylation levels as a function of
      clock time of death and parameterizing these data using cosine functions. We
      determined global statistical significance by permutation. We then related
      rhythms of DNA methylation with rhythms of RNA expression determined by RNA
      sequencing. We found evidence of significant 24-hour rhythmicity of DNA
      methylation. Regions near transcription start sites were enriched for high
      amplitude rhythmic DNA methylation sites, which were in turn time locked to 24
      hour rhythms of RNA expression of nearby genes, with the nadir of methylation
      preceding peak transcript expression by 1-3 hours. Weak ante-mortem rest-activity
      rhythms were associated with lower amplitude DNA methylation rhythms as were
      older age and the presence of Alzheimer's disease. These findings support the
      hypothesis that 24-hour rhythms of DNA methylation, particularly near
      transcription start sites, may play a role in driving 24-hour rhythms of gene
      expression in the human dorsolateral prefrontal cortex, and may be affected by
      age and Alzheimer's disease. 

PMID- 25375878
TI  - Use and diversion of medical marijuana among adults admitted to inpatient
      psychiatry.
AB  - BACKGROUND: Marijuana use is associated with anxiety, depressive, psychotic,
      neurocognitive, and substance use disorders. Many US states are legalizing
      marijuana for medical uses. OBJECTIVE: To determine the prevalence of medical
      marijuana use and diversion among psychiatric inpatients in Colorado. METHODS:
      Some 623 participants (54.6% male) responded to an anonymous 15-item discharge
      survey that assessed age, gender, marijuana use, possession of a medical
      marijuana card, diversion of medical marijuana, perceived substance use problems,
      and effects of marijuana use. Univariate statistics were used to characterize
      participants and their responses. Chi-square tests assessed factors associated
      with medical marijuana registration. RESULTS: Of the total number of respondents,
      282 (47.6%) reported using marijuana in the last 12 months and 60 (15.1%)
      reported having a marijuana card. In comparison to survey respondents who denied
      having a medical marijuana card, those respondents with a medical marijuana card
      were more likely to have initiated use before the age of 25, to be male, to have
      used marijuana in the last 12 months, and to have used at least 20 days in the
      past month. 133 (24.1%) respondents reported that someone with a medical
      marijuana card had shared or sold medical marijuana to them; 24 (41.4%) of
      respondents with a medical marijuana card reported ever having shared or sold
      their medical marijuana. CONCLUSION: Medical marijuana use is much more prevalent
      among adults hospitalized with a psychiatric emergency than in the general
      population; diversion is common. Further studies which correlate amount, dose,
      duration, and strain of use with particular psychiatric disorders are needed.

PMID- 25375881
TI  - MicroRNAs in the failing heart--novel therapeutic targets?
AB  - Heart failure is a common and disabling disease with high mortality that carries
      substantial societal costs. Current therapeutic strategies are aimed at relieving
      symptoms, avoiding hospitalization, and prolonging life, but disease progression
      is ultimately inevitable. MicroRNAs (miRNAs) are short, non-coding RNA molecules
      with pervasive roles in eukaryotic biology, annealing to complimentary sites on
      target mRNAs, and repressing gene expression. The fact that miRNAs are
      dysregulated in many human disorders, including cardiovascular disease, and the
      relative ease with which endogenous miRNA expression can be altered using
      synthetic antisense oligos has stirred enthusiasm for these molecules as
      potential drug targets. The aim of this review article was to summarize the
      current knowledge on the roles of miRNA in the pathophysiology of heart failure
      as well as the use of miRNAs as therapeutic targets and diagnostic tools for the
      disease.

PMID- 25375880
TI  - Enhancement of energy expenditure following a single oral dose of flavan-3-ols
      associated with an increase in catecholamine secretion.
AB  - Numerous clinical studies have reported that ingestion of chocolate reduces the
      risk of metabolic syndrome. However, the mechanisms by which this occurs remain
      unclear. In this murine study, the metabolic-enhancing activity of a 10 mg/kg
      mixture of flavan-3-ol fraction derived from cocoa (FL) was compared with the
      same single dose of (-)-epicatechin (EC). Resting energy expenditure (REE) was
      significantly increased in mice treated with the FL versus the group administered
      the distilled water vehicle (Cont) during periods of ad libitum feeding and
      fasting. Mice were euthanized under the effect of anesthesia 2, 5, and 20 hr
      after treatment with FL or Cont while subsequently fasting. The mRNA levels of
      the uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor
      gamma coactivator-1 alpha (PGC-1alpha) in brown adipose tissue (BAT) were
      significantly increased 2 hr after administration of FL. UCP-3 and PGC-1alpha in
      the gastrocnemius were significantly increased 2 and 5 hr after administration of
      the FL. The concentrations of phosphorylated AMP-activated protein kinase (AMPK)
      1alpha were found to be significant in the gastrocnemius of mice 2 and 5 hr after
      ingesting FL. However, these changes were not observed following treatment with
      EC. Plasma was collected for measurement of catecholamine levels in other animals
      euthanized by decapitation 2 and 4 hr after their respective group treatment.
      Plasma adrenaline level was significantly elevated 2 hr after treatment with FL;
      however, this change was not observed following the administration of EC alone.
      The present results indicated that FL significantly enhanced systemic energy
      expenditure, as evidenced by an accompanying increase in the type of gene
      expression responsible for thermogenesis and lipolysis, whereas EC exhibited this
      less robustly or effectively. It was suggested the possible interaction between
      thermogenic and lipolytic effects and the increase in plasma catecholamine
      concentrations after administration of a single oral dose of FL. 

PMID- 25375882
TI  - Long non-coding RNA and epigenetic gene regulation of KSHV.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8) is a gamma
      herpesvirus linked to Kaposi's sarcoma (KS) and two lymphoproliferative
      disorders, primary effusion lymphoma (PEL or body-cavity B-lymphoma [BCBL]) and a
      subset of Multicentric Castleman's Disease. During lytic growth, pervasive viral
      transcription generating a variety of transcripts with uncertain protein-coding
      potential has been described on a genome-wide scale in beta- and gamma
      herpesviruses. One class of such RNAs is called long non-coding RNAs (lncRNAs).
      KSHV encodes a viral lncRNA known as polyadenylated nuclear RNA (PAN RNA), a
      copious early gene product. PAN RNA has been implicated in KSHV gene expression,
      replication, and immune modulation. PAN RNA expression is required for optimal
      expression of the entire KSHV lytic gene expression program. Latent KSHV episomes
      are coated with viral latency-associated nuclear antigen (LANA). LANA rapidly
      dissociates from episomes during reactivation. Here we review recent studies
      suggesting that PAN RNA may function as a viral lncRNA, including a role in the
      facilitation of LANA-episomal dissociation during lytic replication.

PMID- 25375883
TI  - Epidemiology and transmission of Kaposi's sarcoma-associated herpesvirus.
AB  - This review summarizes the current knowledge pertaining to Kaposi sarcoma
      associated herpesvirus (KSHV) epidemiology and transmission. Since the
      identification of KSHV twenty years ago, it is now known to be associated with
      Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's
      disease. Many studies have been conducted to understand its epidemiology and
      pathogenesis and their results clearly show that the worldwide distribution of
      KSHV is uneven. Some geographical areas, such as sub-Saharan Africa, the
      Mediterranean region and the Xinjiang region of China, are endemic areas, but
      Western Europe and United States have a low prevalence in the general population.
      This makes it imperative to understand the risk factors associated with
      acquisition of infection. KSHV can be transmitted via sexual contact and non
      sexual routes, such as transfusion of contaminated blood and tissues transplants,
      or via saliva contact. There is now a general consensus that salivary
      transmission is the main route of transmission, especially in children residing
      in endemic areas. Therefore, there is a need to better understand the sources of
      transmission to young children. Additionally, lack of animal models to study
      transmission, gold standard serological assay and the lack of emphasis on endemic
      KS research has hampered the efforts to further delineate KSHV transmission in
      order to design effective prevention strategies.

PMID- 25375884
TI  - Cytoplasmic dynein promotes HIV-1 uncoating.
AB  - Retroviral capsid (CA) cores undergo uncoating during their retrograde transport
      (toward the nucleus), and/or after reaching the nuclear membrane. However,
      whether HIV-1 CA core uncoating is dependent upon its transport is not
      understood. There is some evidence that HIV-1 cores retrograde transport involves
      cytoplasmic dynein complexes translocating on microtubules. Here we investigate
      the role of dynein-dependent transport in HIV-1 uncoating. To interfere with
      dynein function, we depleted dynein heavy chain (DHC) using RNA interference, and
      we over-expressed p50/dynamitin. In immunofluorescence microscopy experiments,
      DHC depletion caused an accumulation of CA foci in HIV-1 infected cells. Using a
      biochemical assay to monitor HIV-1 CA core disassembly in infected cells, we
      observed an increase in amounts of intact (pelletable) CA cores upon DHC
      depletion or p50 over-expression. Results from these two complementary assays
      suggest that inhibiting dynein-mediated transport interferes with HIV-1 uncoating
      in infected cells, indicating the existence of a functional link between HIV-1
      transport and uncoating.

PMID- 25375886
TI  - In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial
      agent.
AB  - As part of our drug discovery program for anti-filarial agents from Indian
      medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated,
      which resulted in the isolation and characterization of an anti-filarial agent,
      ursolic acid (UA) as a major constituent. Antifilarial activity of UA against the
      human lymphatic filarial parasite Brugia malayi using in vitro and in vivo
      assays, and in silico docking search on glutathione-s-transferase (GST) parasitic
      enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50:
      8.84 uM) and female adult worms (LC100: 100; IC50: 35.36 uM) as observed by
      motility assay; it exerted 86% inhibition in MTT reduction potential of the adult
      parasites. The selectivity index (SI) of UA for the parasites was found safe.
      This was supported by the molecular docking studies, which showed adequate
      docking (LibDock) scores for UA (-8.6) with respect to the standard antifilarial
      drugs, ivermectin (IVM -8.4) and diethylcarbamazine (DEC-C -4.6) on glutathione-s
      transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies
      showed that UA possesses drug-like properties. Furthermore, UA was evaluated in
      vivo in B. malayi-M. coucha model (natural infection), which showed 54%
      macrofilaricidal activity, 56% female worm sterility and almost unchanged
      microfilaraemia maintained throughout observation period with no adverse effect
      on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate
      that UA is a promising, inexpensive, widely available natural lead, which can be
      designed and developed into a macrofilaricidal drug. To the best of our knowledge
      this is the first ever report on the anti-filarial potential of UA from E.
      tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug'
      tool screening predictions. 

PMID- 25375885
TI  - PAN's Labyrinth: Molecular biology of Kaposi's sarcoma-associated herpesvirus
      (KSHV) PAN RNA, a multifunctional long noncoding RNA.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic gamma-herpesivrus,
      the causative agent of Kaposi's sarcoma and body cavity lymphomas. During
      infection KSHV produces a highly abundant long non-coding polyadenylated RNA that
      is retained in the nucleus known as PAN RNA. Long noncoding RNAs (lncRNA) are key
      regulators of gene expression and are known to interact with specific chromatin
      modification complexes, working in cis and trans to regulate gene expression.
      Data strongly supports a model where PAN RNA is a multifunctional regulatory
      transcript that controls KSHV gene expression by mediating the modification of
      chromatin by targeting the KSHV repressed genome. 

PMID- 25375887
TI  - Theoretical analysis of electrochemical surface-area loss in supported
      nanoparticle catalysts.
AB  - In polymer electrolyte fuel cells a decrease in catalytic surface-area within the
      cathode catalyst layer is a critical barrier to commercialization. This loss in
      catalytic surface-area manifests as a loss in cell voltage and thus power density
      of the cell. It has been established that potential cycling accelerates the loss
      in catalytic surface-area yet isolating the contributing mechanisms as well as
      relating mechanisms to operating conditions is not as straightforward. We
      approach the issue of surface-area loss deconvolution with a combined
      experimental, modelling and theoretical framework. The methodology is based on
      the Lifshitz-Slyozov-Wagner and Smoluchowski theories of particle size
      distribution evolution. Electrochemical surface-area loss experiments probing
      upper potential limits of 0.9 and 1.2 V as well as temperatures from 298 to 343 K
      were analyzed with the model. A dissolution and redeposition mechanism was
      correlated with the measurements for both upper potential limits; however, at the
      upper potential limit of 1.2 V, ambiguity between the coagulation and the
      dissolution and redeposition mechanisms was found. Notwithstanding, the extracted
      dissolution and redeposition parameters aligned with independent studies on Pt
      dissolution whereas similar positive comparisons with independent results were
      unable to be made for the coagulation mechanism. 

PMID- 25375888
TI  - Infrared spectroscopy and 193 nm photochemistry of methylamine isolated in solid
      parahydrogen.
AB  - The in situ UV photolysis of a precursor molecule trapped in a parahydrogen (pH2)
      matrix is a simple method used to generate isolated radical photofragments that
      are well suited for infrared spectroscopic studies. However, for molecules that
      can dissociate via multiple pathways, little is known about how the pH2 matrix
      influences the branching among these open pathways. We report FTIR spectroscopic
      studies of the 193 nm photodecomposition of methylamine (MA, CH3NH2) isolated in
      pH2 quantum matrixes at 1.8 K. We observe single exponential decay of the MA
      precursor upon irradiation and the quantum yield for MA photodissociation is
      measured to be Phi = 0.26(2) consistent with a weak pH2 cage effect. By comparing
      to gas-phase results, we show the in situ photolysis results in greater
      production of molecular products (CH2?NH + H2) compared to radical products
      (CH3NH + H) consistent with the idea of partial caging of the H atom
      photofragments. The information gained in this work can be used to guide future
      photolysis studies in pH2 matrixes. 

PMID- 25375889
TI  - Effects of atrazine in fish, amphibians, and reptiles: an analysis based on
      quantitative weight of evidence.
AB  - A quantitative weight of evidence (WoE) approach was developed to evaluate
      studies used for regulatory purposes, as well as those in the open literature,
      that report the effects of the herbicide atrazine on fish, amphibians, and
      reptiles. The methodology for WoE analysis incorporated a detailed assessment of
      the relevance of the responses observed to apical endpoints directly related to
      survival, growth, development, and reproduction, as well as the strength and
      appropriateness of the experimental methods employed. Numerical scores were
      assigned for strength and relevance. The means of the scores for relevance and
      strength were then used to summarize and weigh the evidence for atrazine
      contributing to ecologically significant responses in the organisms of interest.
      The summary was presented graphically in a two-dimensional graph which showed the
      distributions of all the reports for a response. Over 1290 individual responses
      from studies in 31 species of fish, 32 amphibians, and 8 reptiles were evaluated.
      Overall, the WoE showed that atrazine might affect biomarker-type responses, such
      as expression of genes and/or associated proteins, concentrations of hormones,
      and biochemical processes (e.g. induction of detoxification responses), at
      concentrations sometimes found in the environment. However, these effects were
      not translated to adverse outcomes in terms of apical endpoints. The WoE approach
      provided a quantitative, transparent, reproducible, and robust framework that can
      be used to assist the decision-making process when assessing environmental
      chemicals. In addition, the process allowed easy identification of uncertainty
      and inconsistency in observations, and thus clearly identified areas where future
      investigations can be best directed.

PMID- 25375891
TI  - Role of tumour angiogenesis in haematological malignancies.
AB  - Tumour angiogenesis plays a key role in the pathogenesis and progression of
      haematological malignancies. Thereby, pro- and anti-angiogenic growth factors and
      cytokines regulate the angiogenic process. The most important growth factor,
      vascular endothelial growth factor (VEGF) and its signaling through its receptors
      1 and 2, is not only involved in solid tumours, but there is also emerging
      evidence that tumour progression in haematological malignancies also depends on
      the induction of new blood vessel formation. The evidence supporting this theory
      includes the finding of increased bone marrow microvessel density and increased
      levels of plasma pro-angiogenic cytokines. Leukaemia cells interact with
      surrounding host cells and extracellular matrix, this crosstalk affecting the
      most important aspects of the malignant phenotype. The pathophysiology of
      leukaemia induced angiogenesis involves both direct production of angiogenic
      cytokines by leukaemia cells and their interaction with bone marrow
      microenvironment. The inhibition of VEGF signalling by monoclonal antibodies or
      small molecules (kinase inhibitors) has already been successfully used for the
      treatment of different cancer entities, and multiple new drugs are being tested.
      This review summarises recent advances in the basic understanding of the role of
      angiogenesis in haematological malignancies and the translation of such basic
      findings into clinical studies. 

PMID- 25375890
TI  - Impact of multimorbidity on disability and quality of life in the Spanish older
      population.
AB  - BACKGROUND: Population aging is closely related to high prevalence of chronic
      conditions in developed countries. In this context, health care policies aim to
      increase life span cost-effectively while maintaining quality of life and
      functional ability. There is still, however, a need for further understanding of
      how chronic conditions affect these health aspects. The aim of this paper is to
      assess the individual and combined impact of chronic physical and mental
      conditions on quality of life and disability in Spain, and secondly to show
      gender trends. METHODS: Cross-sectional data were collected from the COURAGE
      study. A total of 3,625 participants over 50 years old from Spain were included.
      Crude and adjusted multiple linear regressions were conducted to detect
      associations between individual chronic conditions and disability, and between
      chronic conditions and quality of life. Separate models were used to assess the
      influence of the number of diseases on the same variables. Additional analogous
      regressions were performed for males and females. RESULTS: All chronic conditions
      except hypertension were statistically associated with poor results in quality of
      life and disability. Depression, anxiety and stroke were found to have the
      greatest impact on outcomes. The number of chronic conditions was associated with
      substantially lower quality of life [beta for 4+ diseases: -18.10 (-20.95,
      15.25)] and greater disability [beta for 4+ diseases: 27.64 (24.99,30.29]. In
      general, women suffered from higher rates of multimorbidity and poorer results in
      quality of life and disability. CONCLUSIONS: Chronic conditions impact greatly on
      quality of life and disability in the older Spanish population, especially when
      co-occurring diseases are added. Multimorbidity considerations should be a
      priority in the development of future health policies focused on quality of life
      and disability. Further studies would benefit from an expanded selection of
      diseases. Policies should also deal with gender idiosyncrasy in certain cases.

PMID- 25375892
TI  - Singlet oxygen photosensitisation by the fluorescent protein Pp2FbFP L30M, a
      novel derivative of Pseudomonas putida flavin-binding Pp2FbFP.
AB  - Flavin-binding fluorescent proteins (FbFPs) are a class of fluorescent reporters
      that have been increasingly used as reporters in the study of cellular structures
      and dynamics. Flavin's intrinsic high singlet oxygen ((1)O2) quantum yield
      (PhiDelta = 0.51) provides a basis for the development of new FbFP mutants
      capable of photosensitising (1)O2 for mechanistic and therapeutic applications,
      as recently exemplified by the FbFP miniSOG. In the present work we report an
      investigation on the (1)O2 photoproduction by Pp2FbFP L30M, a novel derivative of
      Pseudomonas putida Pp2FbFP. Direct detection of (1)O2 through its phosphorescence
      at 1275 nm yielded the value PhiDelta = 0.09 +/- 0.01, which is the highest (1)O2
      quantum yield reported to date for any FP and is approximately 3-fold higher than
      the PhiDelta for miniSOG. Unlike miniSOG, transient absorption measurements
      revealed the existence of two independent triplet states each with a different
      ability to sensitise (1)O2. 

PMID- 25375893
TI  - Which modifiable health risks are associated with changes in productivity costs?
AB  - The purpose of this retrospective, longitudinal study was to assess longitudinal
      associations between modifiable health risks and workplace absenteeism and
      presenteeism and to estimate lost productivity costs. Across the 4-year study
      period (2007-2010), 17,089 unique employees from a large US computer manufacturer
      with a highly technical workforce completed at least 1 health risk assessment.
      Generalized estimating equation models were used to estimate the mean population
      level absenteeism and presenteeism for 11 modifiable health risks and adjust for
      9 sociodemographic and employment-related factors. Because patient age was highly
      correlated with several other variables, the analysis was stratified by age (<45
      vs. >=45 years). For all ages, poor emotional health, inadequate exercise,
      tobacco use, and having a body mass index (BMI) greater than 35 (all P<.05) were
      consistently associated with both absenteeism and presenteeism. Having a BMI over
      35 and poor emotional health were associated with the largest impact in
      absenteeism (0.46 days) and presenteeism (4.03 days), respectively. Younger and
      older workers had similar associations between health risks and presenteeism;
      however, hypertension, blood sugar, inadequate exercise, and alcohol were
      associated (P?.01) with greater absenteeism among older but not younger workers.
      The results suggest that productivity loss is strongly related to emotional
      health and obesity-related health risks (eg, BMI, exercise) but differs by age.
      These findings could help prioritize preventive health programs offered by
      employers at their worksite health centers. Given the aging of the US workforce,
      keeping older workers healthy and productive will be crucial to remaining
      competitive in the global economy. (Population Health Management 2015;18:30-38). 

PMID- 25375894
TI  - A computational study on Lewis acid-catalyzed diastereoselective acyclic radical
      allylation reactions with unusual selectivity dependence on temperature and
      epimer precursor.
AB  - In stereoselective radical reactions, it is accepted that the configuration of
      the radical precursor has no impact on the levels of stereoinduction, as a
      prochiral radical intermediate is planar, with two identical faces, independently
      of its origin. However, Sibi and Rheault (J. Am. Chem. Soc. 2000, 122, 8873-8879)
      remarkably obtained different selectivities in the trapping of radicals
      originated from two epimeric bromides, catalyzed by chelating Lewis acids. The
      selectivity rationalization was made on the basis of different conformational
      properties of each epimer. However, in this paper we show that the two epimers
      have similar conformational properties, which implies that the literature
      proposal is unable to explain the experimental results. We propose an alternative
      mechanism, in which the final selectivity is dependent on different reaction
      rates for radical formation from each epimer. By introducing a different
      perspective of the reaction mechanism, our model also allows the rationalization
      of different chemical yields obtained from each epimer, a result not rationalized
      by the previous model. Adaptation to other radical systems, under different
      reaction conditions, is also possible. 

PMID- 25375895
TI  - Significance of alphaThr-349 in the catalytic sites of Escherichia coli ATP
      synthase.
AB  - This paper describes the role of alpha-subunit VISIT-DG sequence residue alphaThr
      349 in the catalytic sites of Escherichia coli F1Fo ATP synthase. X-ray
      structures show the highly conserved alphaThr-349 in the proximity (2.68 A) of
      the conserved phosphate binding residue betaR182 in the phosphate binding
      subdomain. alphaT349A, -D, -Q, and -R mutations caused 90-100-fold losses of
      oxidative phosphorylation and reduced ATPase activity of F1Fo in membranes.
      Double mutation alphaT349R/betaR182A was able to partially compensate for the
      absence of known phosphate binding residue betaR182. Azide, fluoroaluminate, and
      fluoroscandium caused insignificant inhibition of alphaT349A, -D, and -Q mutants,
      slight inhibition of the alphaT349R mutant, partial inhibition of the
      alphaT349R/betaR182A double mutant, and complete inhibition of the wild type.
      Whereas NBD-Cl (7-chloro-4-nitrobenzo-2-oxa-1,3-diazole) inhibited wild-type
      ATPase and its alphaT349A, -D, -R, and -Q mutants essentially completely,
      betaR182A ATPase and double mutant alphaT349A/betaR182A were inhibited partially.
      Inhibition characteristics supported the conclusion that NBD-Cl reacts in betaE
      (empty) catalytic sites, as shown previously by X-ray structure analysis.
      Phosphate protected against NBD-Cl inhibition in the wild type, alphaT349R, and
      double mutant alphaT349R/betaR182A but not in alphaT349A, alphaT349D, or
      alphaT349Q. The results demonstrate that alphaThr-349 is a supplementary residue
      involved in phosphate binding and transition state stabilization in ATP synthase
      catalytic sites through its interaction with betaR182. 

PMID- 25375896
TI  - The vitamin D analogue ED71 but Not 1,25(OH)2D3 targets HIF1alpha protein in
      osteoclasts.
AB  - Although both an active form of the vitamin D metabolite, 1,25(OH)2D3, and the
      vitamin D analogue, ED71 have been used to treat osteoporosis, anti-bone
      resorbing activity is reportedly seen only in ED71- but not in 1,25(OH)2D3 
      treated patients. In addition, how ED71 inhibits osteoclast activity in patients
      has not been fully characterized. Recently, HIF1alpha expression in osteoclasts
      was demonstrated to be required for development of post-menopausal osteoporosis.
      Here we show that ED71 but not 1,25(OH)2D3, suppress HIF1alpha protein expression
      in osteoclasts in vitro. We found that 1,25(OH)2D3 or ED71 function in
      osteoclasts requires the vitamin D receptor (VDR). ED71 was significantly less
      effective in inhibiting M-CSF and RANKL-stimulated osteoclastogenesis than was
      1,25(OH)2D3 in vitro. Downregulation of c-Fos protein and induction of Ifnbeta
      mRNA in osteoclasts, both of which reportedly block osteoclastogenesis induced by
      1,25(OH)2D3 in vitro, were both significantly higher following treatment with
      1,25(OH)2D3 than with ED71. Thus, suppression of HIF1alpha protein activity in
      osteoclasts in vitro, which is more efficiently achieved by ED71 rather than by
      1,25(OH)2D3, could be a reliable read-out in either developing or screening
      reagents targeting osteoporosis. 

PMID- 25375898
TI  - Recent evidence of underestimated circulation of hepatitis C virus intergenotypic
      recombinant strain RF2k/1b in the Rhone-Alpes region, France, January to August
      2014: implications for antiviral treatment.
AB  - Since the beginning of 2014, hepatitis C virus (HCV) recombinant forms RF2k/1b
      have been detected in the Rhone-Alpes French region in 10 patients originating
      from the Caucasus area. Circulation of this particular HCV strain is very likely
      to be underestimated. It is also prone to be misgenotyped when using genotyping
      methods based on the 5' region of the viral genome, which may lead to suboptimal
      treatment.

PMID- 25375897
TI  - Improved contact predictions using the recognition of protein like contact
      patterns.
AB  - Given sufficient large protein families, and using a global statistical inference
      approach, it is possible to obtain sufficient accuracy in protein residue contact
      predictions to predict the structure of many proteins. However, these approaches
      do not consider the fact that the contacts in a protein are neither randomly, nor
      independently distributed, but actually follow precise rules governed by the
      structure of the protein and thus are interdependent. Here, we present PconsC2, a
      novel method that uses a deep learning approach to identify protein-like contact
      patterns to improve contact predictions. A substantial enhancement can be seen
      for all contacts independently on the number of aligned sequences, residue
      separation or secondary structure type, but is largest for beta-sheet containing
      proteins. In addition to being superior to earlier methods based on statistical
      inferences, in comparison to state of the art methods using machine learning,
      PconsC2 is superior for families with more than 100 effective sequence homologs.
      The improved contact prediction enables improved structure prediction. 

PMID- 25375899
TI  - Exceptionally low rotavirus incidence in the Netherlands in 2013/14 in the
      absence of rotavirus vaccination.
AB  - An unexpected drop in rotavirus (RV) detections was observed in the Netherlands
      in 2014, without RV vaccination. The estimated decrease in RV detections and
      gastroenteritis consultations in under five year-olds, in January-April 2014,
      compared to the same months in previous years, was 72% and 36%, respectively. The
      low birth rate, mild winter, high RV incidence in the previous year and the
      introduction of RV vaccination in neighbouring countries may have contributed to
      this decrease.

PMID- 25375900
TI  - Identification of verocytotoxin-producing Escherichia coli O117:H7 in men who
      have sex with men, England, November 2013 to August 2014.
AB  - Between November 2013 and August 2014, nine cases of verocytotoxin-producing
      Escherichia coli O117:H7 VT1 were confirmed in adult men. Further investigation
      using semi-structured interviews revealed that eight cases were United Kingdom
      (UK)-born men who have sex with men (MSM) who had sexually acquired infection in
      the UK. Most were HIV-positive with high numbers of sexual partners. This
      behavioural profile resembles that associated with the recent rapid increase in
      other sexually acquired infections in MSM.

PMID- 25375902
TI  - Outbreak of hepatitis A infection associated with the consumption of frozen
      berries, Ireland, 2013--linked to an international outbreak.
AB  - In May 2013, a European alert was issued regarding a hepatitis A virus (HAV)
      outbreak in Italy. In June 2013, HAV subgenotype IA with an identical sequence
      was identified in Ireland in three cases who had not travelled to Italy. The
      investigation consisted of descriptive epidemiology, a case-control study,
      microbiological testing of human and food specimens, molecular typing of positive
      specimens and food traceback. We identified 21 outbreak cases (14 confirmed
      primary cases) with symptom onset between 31 January and 11 October 2013. For the
      case-control study, we recruited 11 confirmed primary cases and 42 matched
      controls. Cases were more likely than controls to have eaten berry cheesecake
      (matched odds ratio (mOR): 12; 95% confidence interval (CI): 1.3-114), whole
      frozen berries (mOR: 9.5; 95% CI: 1.0-89), yoghurt containing frozen berries
      (mOR: 6.6, 95% CI: 1.2-37) or raw celery (mOR: 4; 95% CI: 1.2-16). Among cases,
      91% had consumed at least one of four products containing frozen berries (mOR:
      12; 95% CI: 1.5-94). Sixteen food samples tested were all negative for HAV. As
      products containing frozen berries were implicated in the outbreak, the public
      were advised to heat-treat frozen berries before consumption.

PMID- 25375903
TI  - Three simultaneous, food-borne, multi-country outbreaks of hepatitis A virus
      infection reported in EPIS-FWD in 2013: what does it mean for the European Union?
AB  - Between March and May 2013, three multi-country outbreaks of hepatitis A virus
      (HAV) infection were reported through the Epidemic Intelligence Information
      System for Food- and Water-borne diseases (EPIS-FWD) of the European Centre for
      Disease Prevention and Control (ECDC). The aim of this work is to put these
      outbreaks into a European Union (EU) and European Economic Area (EEA) perspective
      and highlight opportunities for improving detection and investigation of such
      outbreaks. Although HAV outbreaks are not unusual in the EU/EEA, having three
      large food-borne multi-country outbreaks declared within three months is an
      unexpected event, particularly when at least two of these outbreaks are
      associated with frozen berries. Factors influencing the occurrence of these
      events include the increased number of susceptible Europeans, the limited
      coverage of HAV vaccination, the global trade of potentially contaminated
      products introduced in the EU/EEA, and the 'awareness chain effect' leading to a
      wave of notifications. Further studies should be conducted to understand the risk
      posed by frozen berries. Laboratory capacity and surveillance of viral infections
      in the EU/EEA, as well as HAV vaccination recommendations to travellers to
      endemic countries should be strengthened. Finally, timely reporting food-borne
      events through EPIS-FWD, to ensure timely response.

PMID- 25375901
TI  - Control of carbapenemase-producing Klebsiella pneumoniae: a region-wide
      intervention.
AB  - Starting in 2010, there was a sharp increase in infections caused by Klebsiella
      pneumoniae resistant to carbapenems in the Emilia-Romagna region in Italy. A
      region-wide intervention to control the spread of carbapenemase-producing K.
      pneumoniae (CPKP) in Emilia-Romagna was carried out, based on a regional
      guideline issued in July 2011. The infection control measures recommended to the
      Health Trusts (HTs) were: phenotypic confirmation of carbapenemase production,
      active surveillance of asymptomatic carriers and contact isolation precautions
      for carriers. A specific surveillance system was activated and the implementation
      of control measures in HTs was followed up. A significant linear increase of
      incident CPKP cases over time (p<0.001) was observed at regional level in Emilia
      Romagna in the pre-intervention period, while the number of cases remained stable
      after the launch of the intervention (p=0.48). Considering the patients
      hospitalised in five HTs that provided detailed data on incident cases, a
      downward trend was observed in incidence after the release of the regional
      guidelines (from 32 to 15 cases per 100,000 hospital patient days). The spread of
      CPKP in Emilia-Romagna was contained by a centrally-coordinated intervention. A
      further reduction in CPKP rates might be achieved by increased compliance with
      guidelines and specific activities of antibiotic stewardship.

PMID- 25375904
TI  - Factors associated with length of stay for pediatric asthma hospitalizations.
AB  - OBJECTIVE: Asthma is a leading cause of pediatric hospitalizations, but little is
      known about factors associated with length of stay (LOS) for asthma
      hospitalizations. The aim of this study was to identify factors associated with
      LOS for pediatric asthma hospitalizations. METHODS: The Pediatric Health
      Information System (PHIS) was used to cohort patients 2-17 years old with a
      primary asthma diagnosis discharged from 42 PHIS hospitals in 2011.
      Sociodemographic, temporal and health-status factors were examined. Bivariate and
      generalized-estimating-equation logistic regression analyses were performed to
      identify factors associated with LOS, after adjusting for severity of illness
      (SOI). RESULTS: In total, 25,900 children were hospitalized, with a mean LOS of
      1.9 days. In bivariate analysis, mean LOS was longer (p < 0.01) for patients with
      complex chronic conditions (CCC) (3.1 days versus 1.8 for non-CCC) and
      adolescents (2.3 versus 1.8 for 2-5 years old). In multivariable analysis,
      obstructive sleep apnea (OSA; OR 2.3; 95% CI: 1.8-2.9), older age (OR 1.3; 95%
      CI: 1.2-1.4), obesity (OR 1.3; 95% CI: 1.1-1.4), CCC (OR 1.3; 95% CI: 1.1-1.4),
      winter admissions (OR 1.2; 95% CI: 1.1-1.4), female gender (OR 1.1; 95% CI: 1.1
      1.3), and weekend admissions (OR 1.1; 95% CI: 1.03-1.2) had higher odds of asthma
      LOS >2 days. CONCLUSIONS: OSA, older age, obesity, CCC, winter and weekend
      admissions, and female gender are associated with longer LOS for pediatric asthma
      hospitalizations, after adjustment for SOI. The study findings suggest that
      interventions focused on these at-risk groups may prove most useful in reducing
      LOS for pediatric asthma hospitalizations.

PMID- 25375905
TI  - Anxiety sensitivity as a mediator of the association between asthma and smoking.
AB  - OBJECTIVE: Despite its negative effects, smoking is more common among individuals
      with asthma compared to those without. Anxiety sensitivity (fear of arousal
      related sensations) is associated with both smoking and asthma; however, no
      research, to date, has examined the interplay between these three factors. Thus,
      the purpose of the current study was to evaluate the mediating role of anxiety
      sensitivity in the association between asthma diagnosis and smoking status.
      METHODS: The current study was a secondary analysis of data from three existing
      datasets of non-smokers and smokers with and without asthma (n = 433; 56.3%
      female, M(age) = 34.01 years, SD = 13.9). Participants provided information on
      their asthma diagnosis status and smoking status and completed self-report
      measures. RESULTS: As hypothesized, after controlling for gender, race and age,
      there was a significant indirect effect of asthma diagnosis on smoking status
      through anxiety sensitivity (95% CI = 0.07-0.48). CONCLUSIONS: These results
      indicate that the association between asthma diagnosis and smoking status appears
      to be driven, in part, by anxiety sensitivity and suggest that anxiety
      sensitivity may serve as an important target for prevention and intervention
      efforts for smokers with asthma.

PMID- 25375906
TI  - Sensitivity of different spirometric tests for detecting airway obstruction in
      childhood asthma.
AB  - OBJECTIVE: The objective of this study was to compare different measures of
      airflow obstruction by spirometry in childhood asthma. The objectives were; (a)
      to compare sensitivity of large airway tests (FEV1 and PEFR) with tests at low
      lung volumes (small airways) (FEF25-75, FEF50 and FEF75); (b) compare within each
      group which individual tests are more sensitive. METHODS: This was a
      retrospective analysis of 2307 spirometry tests performed during outpatient
      visits on 821 doctor-diagnosed asthma patients aged 6-18. Tests were deemed
      acceptable if they were acceptable and repeatable by American Thoracic Society
      (ATS) criteria. RESULTS: In mild obstruction, FEV1 detected 6.8% abnormal tests
      while FEF75 detected 33% (p < 0.0001). In more severe obstruction, the difference
      was more obvious (FEV1 14.8%; FEF75 71%). Tests at low lung volumes (small airway
      tests) were also more sensitive than PEFR. Within groups, FEV1 was more sensitive
      than PEFR in the large airway tests and FEF75 was more sensitive than FEF25-75
      and FEF50 among the tests at low lung volumes (small airway tests). The FEV1/FVC
      ratio correlated more closely with tests at low lung volumes (small airway
      tests), than with large airway tests. CONCLUSIONS: (1) Tests at low lung volumes
      (small airway tests) are more sensitive than large airway tests; (2) Within
      groups, the FEV1 is better than PEFR and FEF75 is better than FEF25-75 or FEF50.

PMID- 25375907
TI  - Evaluation of proteasomal gene polymorphisms in Lithuanian patients with asthma.
AB  - OBJECTIVE: To investigate polymorphisms of proteasomal genes PSMA6 (rs1048990 and
      rs2277460), PSMC6 (rs2295826 and rs2295827) and PSMA3 (rs2348071) in Lithuanian
      patients with asthma. METHODS: One-hundred forty-six asthma patients and 150
      control subjects were studied. DNA was extracted from peripheral blood samples.
      Five single nucleotide polymorphisms (SNP's) of the three proteasomal genes were
      analyzed using allele-specific amplification or the cleaved amplified polymorphic
      sequence method. RESULTS: While certain alleles and genotypes of PSMA6 rs2277460
      and rs1048990 and PSMA3 rs2348071 SNP's occurred more frequently in asthma
      patients than in controls, no statistically significant differences in alleles or
      genotypes of PSMA6, PSMC6 or PSMA3 were observed between asthma patients and
      control subjects. However, when male and female study subjects were considered
      separately, we found that the CG genotype of PSMA6 rs1048990 is significantly
      more frequent in male asthma patients compared to male control subjects.
      CONCLUSIONS: We found no significant differences in frequencies of selected five
      proteasomal gene PSMA6, PSMC6 and PSMA3 SNP's between asthma patients and control
      subjects overall. Among male subjects, however, the CG PSMA6 rs1048990 genotype
      was significantly more frequent in asthma patients compared with control
      subjects.

PMID- 25375908
TI  - Targeting aldose reductase for the treatment of diabetes complications and
      inflammatory diseases: new insights and future directions.
AB  - Aldose reductase (AR) is an aldo-keto reductase that has been widely investigated
      as an enzyme crucially involved in the pathogenesis of chronic complications
      associated with diabetes mellitus. Recently it was established that AR also acts
      as a key mediator of certain oxidative and inflammatory signaling pathways that
      are involved in the development of different human pathologies, such as
      cardiovascular disorders, sepsis, and cancer. These findings have renewed
      interest in the search for new AR inhibitors (ARIs) with improved profiles as
      potential therapeutic agents. In this review, recent advances in the field and
      promising future directions for developing ARIs are discussed. 

PMID- 25375910
TI  - Course correction.

PMID- 25375909
TI  - The positive regulatory roles of the TIFY10 proteins in plant responses to
      alkaline stress.
AB  - The TIFY family is a novel plant-specific protein family, and is characterized by
      a conserved TIFY motif (TIFF/YXG). Our previous studies indicated the potential
      roles of TIFY10/11 proteins in plant responses to alkaline stress. In the current
      study, we focused on the regulatory roles and possible physiological and
      molecular basis of the TIFY10 proteins in plant responses to alkaline stress. We
      demonstrated the positive function of TIFY10s in alkaline responses by using the
      AtTIFY10a and AtTIFY10b knockout Arabidopsis, as evidenced by the relatively
      lower germination rates of attify10a and attify10b mutant seeds under alkaline
      stress. We also revealed that ectopic expression of GsTIFY10a in Medicago sativa
      promoted plant growth, and increased the NADP-ME activity, citric acid content
      and free proline content but decreased the MDA content of transgenic plants under
      alkaline stress. Furthermore, expression levels of the stress responsive genes
      including NADP-ME, CS, H+-ppase and P5CS were also up-regulated in GsTIFY10a
      transgenic plants under alkaline stress. Interestingly, GsTIFY10a overexpression
      increased the jasmonate content of the transgenic alfalfa. In addition, we showed
      that neither GsTIFY10a nor GsTIFY10e exhibited transcriptional activity in yeast
      cells. However, through Y2H and BiFc assays, we demonstrated that GsTIFY10a, not
      GsTIFY10e, could form homodimers in yeast cells and in living plant cells. As
      expected, we also demonstrated that GsTIFY10a and GsTIFY10e could heterodimerize
      with each other in both yeast and plant cells. Taken together, our results
      provided direct evidence supporting the positive regulatory roles of the TIFY10
      proteins in plant responses to alkaline stress. 

PMID- 25375911
TI  - Tumor sequencing takes off, but insurance reimbursement lags.

PMID- 25375913
TI  - FDA's post-approval studies continue to suffer delays and setbacks.

PMID- 25375914
TI  - As funds to sync health records dwindle, research could suffer.

PMID- 25375916
TI  - Lrp5 regulation of bone mass and serotonin synthesis in the gut.

PMID- 25375917
TI  - Reply to Lrp5 regulation of bone mass and gut serotonin synthesis.

PMID- 25375918
TI  - Colorectal cancer classification based on gene expression is not associated with
      FOLFIRI response.

PMID- 25375919
TI  - Reply to Colorectal cancer classification based on gene expression is not
      associated with FOLFIRI response.

PMID- 25375920
TI  - Megakaryocytes in the hematopoietic stem cell niche.

PMID- 25375921
TI  - Fatty acid synthesis tips the TH17-Treg cell balance.

PMID- 25375922
TI  - Asparagine endopeptidase cleaves tau and promotes neurodegeneration.

PMID- 25375923
TI  - Osteoclast progenitors promote bone vascularization and osteogenesis.

PMID- 25375929
TI  - Whole genome sequence of the Treponema pallidum subsp. endemicum strain Bosnia A:
      the genome is related to yaws treponemes but contains few loci similar to
      syphilis treponemes.
AB  - BACKGROUND: T. pallidum subsp. endemicum (TEN) is the causative agent of bejel
      (also known as endemic syphilis). Clinical symptoms of syphilis and bejel are
      overlapping and the epidemiological context is important for correct diagnosis of
      both diseases. In contrast to syphilis, caused by T. pallidum subsp. pallidum
      (TPA), TEN infections are usually spread by direct contact or contaminated
      utensils rather than by sexual contact. Bejel is most often seen in western
      Africa and in the Middle East. The strain Bosnia A was isolated in 1950 in
      Bosnia, southern Europe. METHODOLOGY/PRINCIPAL FINDINGS: The complete genome of
      the Bosnia A strain was amplified and sequenced using the pooled segment genome
      sequencing (PSGS) method and a combination of three next-generation sequencing
      techniques (SOLiD, Roche 454, and Illumina). Using this approach, a total
      combined average genome coverage of 513* was achieved. The size of the Bosnia A
      genome was found to be 1,137,653 bp, i.e. 1.6-2.8 kbp shorter than any previously
      published genomes of uncultivable pathogenic treponemes. Conserved gene synteny
      was found in the Bosnia A genome compared to other sequenced syphilis and yaws
      treponemes. The TEN Bosnia A genome was distinct but very similar to the genome
      of yaws-causing T. pallidum subsp. pertenue (TPE) strains. Interestingly, the TEN
      Bosnia A genome was found to contain several sequences, which so far, have been
      uniquely identified only in syphilis treponemes. CONCLUSIONS/SIGNIFICANCE: The
      genome of TEN Bosnia A contains several sequences thought to be unique to TPA
      strains; these sequences very likely represent remnants of recombination events
      during the evolution of TEN treponemes. This finding emphasizes a possible role
      of repeated horizontal gene transfer between treponemal subspecies in shaping the
      Bosnia A genome.

PMID- 25375930
TI  - Sites of origin of oral cavity cancer in nonsmokers vs smokers: possible evidence
      of dental trauma carcinogenesis and its importance compared with human
      papillomavirus.
AB  - IMPORTANCE: The relatively high and possibly rising incidence of mouth squamous
      cell carcinoma in nonsmokers, especially women, without obvious cause has been
      noted by previous authors. Is chronic dental trauma and irritation a carcinogen,
      and what is its importance compared with human papillomavirus (HPV) oropharyngeal
      cancer in nonsmokers? OBJECTIVE: To determine whether oral cavity cancers
      occurred more commonly at sites of dental trauma and how the position of these
      cancers varied between nonsmokers lacking major identified carcinogens and
      smokers. If these cancers occurred more frequently at sites of chronic trauma,
      especially in nonsmokers, it would suggest chronic dental trauma as a possible
      carcinogen. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 881
      patients with oral cavity or oropharyngeal cancers seen through a tertiary
      referral hospital between 2001 and 2011 was performed. MAIN OUTCOMES AND
      MEASURES: Patient medical records were analyzed to determine the location of the
      tumor within the oral cavity and oropharynx and how it relates to patient
      demographics, smoking and alcohol histories, and comorbidities. Dental histories
      were also sought, including use of dentures. RESULTS: Nonsmokers comprised 87 of
      390 patients with mouth cancer (22%) and 48 of 334 patients with oropharyngeal
      cancer (14%). Female nonsmoking patients included 53 with oral cancer (61%) but
      only 12 with oropharyngeal squamous cell carcinoma (25%). Oral cancers occurred
      on the lateral tongue, a potential site of chronic dental trauma, in 57
      nonsmokers (66%) compared with 107 smokers/ex-smokers (33%) (P < .001). Gingival
      and floor of mouth lesions occurred in older patients, possibly from chronic
      denture rubbing. Twenty-six patients had dental abnormalities recorded in close
      proximity to where their tumor developed. CONCLUSIONS AND RELEVANCE: Oral cavity
      cancers occur predominantly at sites of potential dental and denture trauma,
      especially in nonsmokers without other risk factors. Recognizing teeth irritation
      as a potential carcinogen would have an impact on prevention and treatment
      strategies.

PMID- 25375928
TI  - Ubiquitination in disease pathogenesis and treatment.
AB  - Ubiquitination is crucial for a plethora of physiological processes, including
      cell survival and differentiation and innate and adaptive immunity. In recent
      years, considerable progress has been made in the understanding of the molecular
      action of ubiquitin in signaling pathways and how alterations in the ubiquitin
      system lead to the development of distinct human diseases. Here we describe the
      role of ubiquitination in the onset and progression of cancer, metabolic
      syndromes, neurodegenerative diseases, autoimmunity, inflammatory disorders,
      infection and muscle dystrophies. Moreover, we indicate how current knowledge
      could be exploited for the development of new clinical therapies. 

PMID- 25375931
TI  - Oxygen pathway modeling estimates high reactive oxygen species production above
      the highest permanent human habitation.
AB  - The production of reactive oxygen species (ROS) from the inner mitochondrial
      membrane is one of many fundamental processes governing the balance between
      health and disease. It is well known that ROS are necessary signaling molecules
      in gene expression, yet when expressed at high levels, ROS may cause oxidative
      stress and cell damage. Both hypoxia and hyperoxia may alter ROS production by
      changing mitochondrial Po2 (PmO2). Because PmO2 depends on the balance between O2
      transport and utilization, we formulated an integrative mathematical model of O2
      transport and utilization in skeletal muscle to predict conditions to cause
      abnormally high ROS generation. Simulations using data from healthy subjects
      during maximal exercise at sea level reveal little mitochondrial ROS production.
      However, altitude triggers high mitochondrial ROS production in muscle regions
      with high metabolic capacity but limited O2 delivery. This altitude roughly
      coincides with the highest location of permanent human habitation. Above 25,000
      ft., more than 90% of exercising muscle is predicted to produce abnormally high
      levels of ROS, corresponding to the "death zone" in mountaineering.

PMID- 25375932
TI  - Neuromuscular fatigue and tibiofemoral joint biomechanics when transitioning from
      non-weight bearing to weight bearing.
AB  - CONTEXT: Fatigue is suggested to be a risk factor for anterior cruciate ligament
      injury. Fatiguing exercise can affect neuromuscular control and laxity of the
      knee joint, which may render the knee less able to resist externally applied
      loads. Few authors have examined the effects of fatiguing exercise on knee
      biomechanics during the in vivo transition of the knee from non-weight bearing to
      weight bearing, the time when anterior cruciate ligament injury likely occurs.
      OBJECTIVE: To investigate the effect of fatiguing exercise on tibiofemoral joint
      biomechanics during the transition from non-weight bearing to early weight
      bearing. DESIGN: Cross-sectional study. SETTING: Research laboratory. PATIENTS OR
      OTHER PARTICIPANTS: Ten participants (5 men and 5 women; age = 25.3 +/- 4.0
      years) with no previous history of knee-ligament injury to the dominant leg.
      INTERVENTION(S): Participants were tested before (preexercise) and after
      (postexercise) a protocol consisting of repeated leg presses (15 repetitions from
      10 degrees -40 degrees  of knee flexion, 10 seconds' rest) against a 60% body
      weight load until they were unable to complete a full bout of repetitions. MAIN
      OUTCOME MEASURE(S): Electromagnetic sensors measured anterior tibial translation
      and knee-flexion excursion during the application of a 40% body-weight axial
      compressive load to the bottom of the foot, simulating weight acceptance. A force
      transducer recorded axial compressive force. RESULTS: The axial compressive force
      (351.8 +/- 44.3 N versus 374.0 +/- 47.9 N; P = .018), knee-flexion excursion (8.0
      degrees  +/- 4.0 degrees  versus 10.2 degrees  +/- 3.7 degrees ; P = .046), and
      anterior tibial translation (6.7 +/- 1.7 mm versus 8.2 +/- 1.9 mm; P < .001)
      increased from preexercise to postexercise. No significant correlations were
      noted. CONCLUSIONS: Neuromuscular fatigue may impair initial knee-joint
      stabilization during weight acceptance, leading to greater accessory motion at
      the knee and the potential for greater anterior cruciate ligament loading.

PMID- 25375934
TI  - Influence of lithium concentration on the structure and Li+ transport properties
      of cubic phase lithium garnets.
AB  - To understand the influence of lithium concentration on the structure and Li(+)
      transport properties of cubic lithium garnets, systematic AC impedance, Raman and
      powder X-ray diffraction (PXRD) investigations have been carried out on lithium
      garnets with nominal compositions LixA3B2O12 (A = Y(3+), La(3+), Sr(2+), Ba(2+);
      B = Te(6+), Ta(5+), Zr(4+) and 3 <=x<= 7.5). The size of the three dimensional
      A3B2O12 frame is found to be an important factor in determining the capacity of
      housing and the nature of distribution of lithium atoms among available
      tetrahedral and octahedral sites in the cubic LixA3B2O12 lithium garnets. The
      Li(+) conduction in a cubic phase lithium garnet is primarily dependent upon the
      concentration of lithium and the nature of distribution of lithium atoms among
      tetrahedral and octahedral sites. AC impedance analysis of cubic phase LixA3B2O12
      revealed an increase in the hopping of Li(+) with the increase in Li(+)
      concentration, reaches a maximized value for the nominal composition Li7La3Zr2O12
      and then decreases with the further increase of lithium concentration. 

PMID- 25375933
TI  - Altered fronto-striatal fiber topography and connectivity in obsessive-compulsive
      disorder.
AB  - Fronto-striatal circuits are hypothesized to be involved in the pathophysiology
      of obsessive-compulsive disorder (OCD). Within this circuitry, ventral frontal
      regions project fibers to the ventral striatum (VS) and dorsal frontal regions to
      the dorsal striatum. Resting state fMRI research has shown higher functional
      connectivity between the orbitofrontal cortex (OFC) and the dorsal part of the VS
      in OCD patients compared to healthy controls (HC). Therefore, we hypothesized
      that in OCD the OFC predominantly project fibers to the more dorsal part of the
      VS, and that the structural connectivity between the OFC and VS is higher
      compared to HC. A total of 20 non-medicated OCD patients and 20 HC underwent
      diffusion-weighted imaging. Connectivity-based parcellation analyses were
      performed with the striatum as seed region and the OFC, dorsolateral prefrontal
      cortex, and dorsal anterior cingulate cortex as target regions. Obtained
      connectivity maps for each frontal region of interest (ROI) were normalized into
      standard space, and Z-component (dorsal-ventral) coordinate of center-of-gravity
      (COG) were compared between two groups. Probabilistic tractography was performed
      to investigate diffusion indices of fibers between the striatum and frontal ROIs.
      COG Z-component coordinates of connectivity maps for OFC ROI were located in the
      more dorsal part of the VS in OCD patients compared to HC. Fractional anisotropy
      of fibers between the OFC and the striatum was higher in OCD patients compared to
      HC. Part of the pathophysiology of OCD might be understood by altered topography
      and structural connectivity of fibers between the OFC and the striatum. 

PMID- 25375935
TI  - The mediating role of work-related musculoskeletal disorders on the link between
      psychosocial factors and absenteeism among administrative workers.
AB  - This study aimed to investigate the association between psychosocial factors
      (i.e., job demand, decision latitude, social support, physical environment, and
      personal risk factors), work-related musculoskeletal disorders (WRMDs), and
      productivity as measured by workers' perceived absenteeism. Data were collected
      from the selected administrative workers (administrative assistant) and analyzed
      using cross tabulation. The results indicate that all psychological factors are
      not significantly associated with WRMDs, except for the association between
      personal risk factors and hip/thigh disorders. Subsequently, WRMDs do not
      significantly contribute to explaining absenteeism. The managerial and research
      implications of this study are deliberately discussed. 

PMID- 25375937
TI  - Testing for associations between hematozoa infection and mercury in wading bird
      nestlings.
AB  - Several wading bird species in the southeastern US have a history of infection by
      hematozoa/avian malaria as well as mercury accumulation through their diet, and
      thus may be exposed to two, generally sublethal, yet chronic, stressors. We
      analyzed nestling wading birds (n = 171) of varying size and trophic position
      from the southeastern US, and a smaller sample (n = 23) of older, free-ranging
      birds, to look for potential interrelationships between infection by hematozoa
      and mercury (Hg) uptake. Only one nestling was PCR positive for hematozoa
      (Plasmodium/Haemoproteus) whereas nine (39%) of the older wading birds were
      positive. Sequencing indicated that both nestling and adult positives were
      infected with Plasmodium. Given the low infection rate of the nestlings, there
      was no association between Hg and malaria. The older birds exhibited a possible
      malaria/Hg association, but it may be confounded by their greater potential
      exposure period and large-scale movements.

PMID- 25375936
TI  - Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult
      mouse.
AB  - BACKGROUND: Microcystins LR (MC-LR) are hepatotoxic cyanotoxins that have been
      shown to induce reproductive toxicity, and Hypothalamic-Pituitary-Gonadal Axis
      (HPG) is responsible for the control of reproductive functions. However, few
      studies have been performed to evaluate the effects of MC-LR on HPG axis. This
      study aimed to investigate the MC-LR-induced toxicity in the reproductive system
      of mouse and focus on the HPG axis. METHODS: Adult male C57BL/6 mice were exposed
      to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 ug/kg body
      weight per day) for 1 to 14 days, and it was found that exposure to different
      concentrations of MC-LR significantly disturbed sperm production in the mice
      testes in a dose- and time-dependent manner. To elucidate the associated possible
      mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH)
      and luteinizing hormone (LH) were assessed. Meanwhile, PCR assays were employed
      to detect alterations in a series of genes involved in HPG axis, such as FSH, LH,
      gonadotropin-releasing hormone (GnRH) and their complement receptors.
      Furthermore, the effect of MC-LR on the viability and testosterone production of
      Leydig cells were tested in vitro. RESULTS: MC-LR significantly impaired the
      spermatogenesis of mice possibly through the direct or indirect inhibition of
      GnRH synthesis at the hypothalamic level, which resulted in reduction of serum
      levels of LH that lead to suppression of testosterone production in the testis of
      mice. CONCLUSIONS: MC-LR may be a GnRH toxin that would disrupt the reproductive
      system of mice.

PMID- 25375938
TI  - Bighorn sheep (Ovis canadensis) sinus tumors are associated with coinfections by
      potentially pathogenic bacteria in the upper respiratory tract.
AB  - Bighorn sheep (Ovis canadensis) sinus tumors are hyperplastic to neoplastic,
      predominantly stromal masses of the paranasal sinuses that expand the sinus
      lining and obstruct the sinus cavities. Obstruction of the sinus cavities and
      disruption of normal sinus lining anatomy may interfere with clearance of
      bacterial pathogens from the upper respiratory tract. To examine this
      possibility, we explored whether the presence of sinus tumor features (tumor
      score) affected the likelihood of detecting potentially pathogenic bacteria from
      upper respiratory sinus lining tissues in bighorn sheep. We developed or used
      existing PCR assays for the detection of leukotoxigenic Pasteurellaceae and
      Mycoplasma ovipneumoniae in sinus lining tissues collected from 97 bighorn sheep
      in Colorado, US from 2009 to 2012. With the use of logistic regression analyses
      we found that tumor score was a good predictor of the probability of detecting
      potentially pathogenic bacteria in sinus lining tissues; we were more likely to
      detect potentially pathogenic bacteria from samples with high tumor scores. These
      findings add to our understanding of possible mechanisms for the maintenance and
      shedding of bacterial agents from the upper respiratory tracts of bighorn sheep.

PMID- 25375939
TI  - Prevalence and genotype identification of Toxoplasma gondii in wild animals from
      southwestern Spain.
AB  - We used PCR to detect Toxoplasma gondii in the principal game species in
      southwestern Spain. We detected T. gondii in 32.2% of animals tested. Prevalences
      varied from 14.7% in wild boar (Sus scrofa) to 51.2% in red fox (Vulpes vulpes).
      The most prevalent genotype was type II (50.0%), followed by type III (20.6%) and
      type I (5.9%). Mixed infections (11.8%) were detected in wild boar (types I+III)
      and red fox (types II+III). Polymorphic strains (11.8%) were detected in several
      species. The high prevalence and the genetic variability shown could have
      implications for infection of farm animals and humans.

PMID- 25375940
TI  - The fungus Trichophyton redellii sp. Nov. Causes skin infections that resemble
      white-nose syndrome of hibernating bats.
AB  - Before the discovery of white-nose syndrome (WNS), a fungal disease caused by
      Pseudogymnoascus destructans, there were no reports of fungal skin infections in
      bats during hibernation. In 2011, bats with grossly visible fungal skin
      infections similar in appearance to WNS were reported from multiple sites in
      Wisconsin, US, a state outside the known range of P. destructans and WNS at that
      time. Tape impressions or swab samples were collected from affected areas of skin
      from bats with these fungal infections in 2012 and analyzed by microscopy,
      culture, or direct DNA amplification and sequencing of the fungal internal
      transcribed spacer region (ITS). A psychrophilic species of Trichophyton was
      isolated in culture, detected by direct DNA amplification and sequencing, and
      observed on tape impressions. Deoxyribonucleic acid indicative of the same fungus
      was also detected on three of five bat carcasses collected in 2011 and 2012 from
      Wisconsin, Indiana, and Texas, US. Superficial fungal skin infections caused by
      Trichophyton sp. were observed in histopathology for all three bats. Sequencing
      of the ITS of Trichophyton sp., along with its inability to grow at 25 C,
      indicated that it represented a previously unknown species, described herein as
      Trichophyton redellii sp. nov. Genetic diversity present within T. redellii
      suggests it is native to North America but that it had been overlooked before
      enhanced efforts to study fungi associated with bats in response to the emergence
      of WNS.

PMID- 25375941
TI  - The role of one health in wildlife conservation: a challenge and opportunity.
AB  - Numerous emerging infectious diseases (EIDs) have arisen from or been identified
      in wildlife, with health implications for both humans and wildlife. In the
      practice of wildlife conservation, to date most attention has focused on the
      threat EIDs pose to biodiversity and wildlife population viability. In the
      popular media and public eye, however, wildlife is often only portrayed as the
      cause of EIDs and resultant human health impacts. There is little coverage on the
      roles of human-induced habitat destruction or wildlife population stress in EID
      spread, nor the negative impacts of disease on wildlife. Here, we focus on a
      little-studied and seldom discussed concern: how real and perceived risks of
      wildlife-associated diseases for human and companion animal health might erode
      public support for wildlife conservation. We believe that wildlife-associated
      EIDs and public perceptions of these risks are among the most important threats
      to wildlife conservation. In light of this concern, we explore the challenges and
      opportunities for addressing this situation in a One Health context that
      emphasizes the interdisciplinary collaboration and the inextricable nature of
      human and animal health and disease.

PMID- 25375942
TI  - Endocarditis associated with Wohlfahrtiimonas chitiniclastica in a short-beaked
      common dolphin (Delphinus delphis).
AB  - Wohlfahrtiimonas chitiniclastica is a rare cause of fatal septicemia in humans,
      and recently reported in a white-tailed deer (Odocoileus virginianus). We
      describe fatal septicemia associated with W. chitiniclastica in a short-beaked
      common dolphin (Delphinus delphis) with fibrinosuppurative and necrotizing
      pulmonic, aortic, and mitral valve endocarditis.

PMID- 25375943
TI  - Prevalence and spatio-temporal variation of an alopecia syndrome in polar bears
      (Ursus maritimus) of the southern Beaufort Sea.
AB  - Alopecia (hair loss) has been observed in several marine mammal species and has
      potential energetic consequences for sustaining a normal core body temperature,
      especially for Arctic marine mammals routinely exposed to harsh environmental
      conditions. Polar bears (Ursus maritimus) rely on a thick layer of adipose tissue
      and a dense pelage to ameliorate convective heat loss while moving between sea
      ice and open water. From 1998 to 2012, we observed an alopecia syndrome in polar
      bears from the southern Beaufort Sea of Alaska that presented as bilaterally
      asymmetrical loss of guard hairs and thinning of the undercoat around the head,
      neck, and shoulders, which, in severe cases, was accompanied by exudation and
      crusted skin lesions. Alopecia was observed in 49 (3.45%) of the bears sampled
      during 1,421 captures, and the apparent prevalence varied by years with peaks
      occurring in 1999 (16%) and 2012 (28%). The probability that a bear had alopecia
      was greatest for subadults and for bears captured in the Prudhoe Bay region, and
      alopecic individuals had a lower body condition score than unaffected
      individuals. The cause of the syndrome remains unknown and future work should
      focus on identifying the causative agent and potential effects on population
      vital rates.

PMID- 25375944
TI  - Identification of a novel herpesvirus associated with a penile proliferative
      lesion in a beluga (Delphinapterus leucas).
AB  - The carcass of an adult male beluga (Delphinapterus leucas) was found beach cast
      in 2008 on the shore of the St. Lawrence Estuary at Riviere-Ouelle, Quebec,
      Canada. The carcass was transported to the Faculte de medecine veterinaire of the
      Universite de Montreal for postmortem examination. Aspiration pneumonia was the
      probable cause of death. Necropsy revealed a focal papilloma-like penile lesion,
      characterized by focal mucosal thickening with disorganization of the epithelial
      layers and lymphoplasmacytic infiltration. A pan-herpesvirus nested PCR assay on
      frozen tissue from the penile lesion was positive. The PCR product sequencing
      revealed a partial herpesvirus DNA polymerase (DPOL) gene sequence of 600
      nucleotides. Its nearest nucleotide identity was with the partial DPOL gene of an
      alphaherpesvirus, bovine herpesvirus 5 (79.5% identity). It also shared high
      identity with several other marine mammal herpesviruses (50.2 to 77.3% identity).
      This new herpesvirus was tentatively named beluga whale herpesvirus (BWHV). Virus
      isolation was unsuccessful. The pathogenic potential of BWHV is unknown, but the
      evaluation of archived tissues suggests that the virus is endemic in the St.
      Lawrence Estuary beluga population.

PMID- 25375945
TI  - Serologic evidence for selected infectious diseases in Marsican brown bears
      (Ursus arctos marsicanus) in Italy (2004-09).
AB  - We tested 30 serum samples collected during 2004-09 from 22 free-ranging Marsican
      brown bears (Ursus arctos marsicanus) in the National Park of Abruzzo, Lazio, and
      Molise, Italy, for antibodies against canine distemper virus (CDV), canine
      adenovirus type 2 (CAV-2), canine parvovirus type 2 (CPV-2), Brucella spp., and
      eight Leptospira interrogans sensu lato serovars. Antibody to CDV was detected in
      11 samples (37%); only two bears (10%) had detectable CAV-2 and Brucella spp.
      antibodies; three bears were positive for L. interrogans serovar Bratislava; and
      one sample had antibody against L. interrogans serovar Copenhageni. All samples
      were positive for CPV-2 antibody. The CPV-2 antibody titers varied from 1?640 to
      1?10,240, suggesting that transmission was still active. Fifty percent of bears
      were positive for antibody to two or more pathogens. Our results highlight the
      need to consider infectious diseases as a potential risk for Marsican brown bear
      conservation.

PMID- 25375946
TI  - Nontarget mortality of New Zealand lesser short-tailed bats (Mystacina
      tuberculata) caused by diphacinone.
AB  - Primary and secondary poisoning of nontarget wildlife with second-generation
      anticoagulant rodenticides has led to restrictions on their use and to increased
      use of first-generation anticoagulants, including diphacinone. Although first
      generation anticoagulants are less potent and less persistent than second
      generation compounds, their use is not without risks to nontarget species. We
      report the first known mortalities of threatened New Zealand lesser short-tailed
      bats (Mystacina tuberculata) caused by diphacinone intoxication. The mortalities
      occurred during a rodent control operation in Pureora Forest Park, New Zealand,
      during the 2008-09 Austral summer. We observed 115 lesser short-tailed bat deaths
      between 9 January and 6 February 2009, and it is likely that many deaths were
      undetected. At necropsy, adult bats showed gross and histologic hemorrhages
      consistent with coagulopathy, and diphacinone residues were confirmed in 10 of 12
      liver samples tested. The cause of mortality of pups was diagnosed as a
      combination of the effects of diphacinone toxicity, exposure, and starvation.
      Diphacinone was also detected in two of 11 milk samples extracted from the
      stomachs of dead pups. Eight adults and 20 pups were moribund when found. Two
      adults and five pups survived to admission to a veterinary hospital. Three pups
      responded to treatment and were released at the roost site on 17 March 2009. The
      route of diphacinone ingestion by adult bats is uncertain. Direct consumption of
      toxic bait or consumption of poisoned arthropod prey could have occurred. We
      suggest that the omnivorous diet and terrestrial feeding habits of lesser short
      tailed bats make them susceptible to poisoning with the bait matrix and the
      method of bait delivery used. We recommend the use of alternative vertebrate
      pesticides, bait matrices, and delivery methods in bat habitat.

PMID- 25375947
TI  - Testicular lesions and antler abnormalities in Colorado, USA mule deer
      (Odocoileus hemionus): a possible role for epizootic hemorrhagic disease virus.
AB  - Antler abnormalities of deer and other cervids often result from testicular
      lesions and decreased levels of testosterone, inhibiting normal cycles of antler
      growth. Affected males have antlers with retained velvet, numerous short,
      misshapen points ("cactus bucks"), and failure to shed these abnormal antlers
      annually. In Colorado, US, we observed a high occurrence of "cactus bucks" in
      mule deer (Odocoileus hemionus) populations after management efforts to increase
      the number of mature male deer in the state. Affected males consistently had
      antibody to epizootic hemorrhagic disease virus serotype 2 (EHDV-2), and
      examination of the testes of these animals demonstrated nonspecific end-stage
      lesions of chronic inflammation, fibrosis, and mineralization. To examine more
      acute stages of testicular lesions, and to screen for EHDV specifically within
      the testes, we sampled 16 male mule deer from affected herds, but with
      essentially normal antlers (n = 14) or retained velvet only (n = 2). Testicular
      and epididymal lesions identified from these samples included necrotizing
      vasculitis (n = 2), hemorrhage (n = 6), edema (n = 2), seminiferous tubular
      necrosis (n = 5), orchitis (n = 5), epididymitis (n = 10), hypospermia (n = 6),
      and end-stage lesions of seminiferous tubular loss (n = 2), fibrosis (n = 2), and
      mineralization (n = 2). Each of the 16 cases was blindly scored on the basis of
      number of histologic lesions, with a median score of two. Five of seven (71%)
      testes that were PCR positive for EHDV had lesion scores above the median,
      whereas none of the nine (0%) EHDV PCR-negative testes had lesion scores above
      the median, suggesting an association between testicular lesions and detection of
      EHDV RNA in the testes (P = 0.003). Although the role of EHDV infection remains
      unconfirmed, the association between testicular and epididymal lesions and
      presence of EHDV RNA in the affected tissues suggests that cactus buck antlers
      may be a sequela of EHDV infection.

PMID- 25375948
TI  - Mycoplasma agassizii in Morafka's desert tortoise (Gopherus morafkai) in Mexico.
AB  - We conducted health evaluations of 69 wild and 22 captive Morafka's desert
      tortoises (Gopherus morafkai) in Mexico between 2005 and 2008. The wild tortoises
      were from 11 sites in the states of Sonora and Sinaloa, and the captive tortoises
      were from the state-managed Centro Ecologico de Sonora Zoo in Hermosillo and a
      private residence in the town of Alamos. We tested 88 tortoises for mycoplasmal
      upper respiratory tract disease (URTD) using enzyme-linked immunosorbent assays
      for specific antibody and by culture and PCR for detection of Mycoplasma
      agassizii and Mycoplasma testudineum. Fifteen of 22 captive tortoises had one or
      more positive diagnostic test results for M. agassizii whereas no wild tortoises
      had positive tests. Tortoises with positive tests also had significantly more
      moderate and severe clinical signs of mycoplasmosis on beaks and nares compared
      to tortoises with negative tests. Captive tortoises also exhibited significantly
      more clinical signs of illness than did wild tortoises, including lethargy and
      moderate to severe ocular signs. The severity of trauma and diseases of the shell
      and integument did not differ significantly among tortoises by site; however,
      clinical signs of moderate to severe trauma and disease were more prevalent in
      older tortoises. Similar to research findings for other species in the genus
      Gopherus in the US, we found that URTD is an important disease in captive
      tortoises. If they escape or are released by intention or accident to the wild,
      captive tortoises are likely to pose risks to healthy, naive wild populations.

PMID- 25375949
TI  - Hematology, serum chemistry, and serum protein electrophoresis ranges for free
      ranging roe deer (Capreolus capreolus) in Sweden.
AB  - We present the first reference ranges for hematology (n = 35 animals), serum
      biochemistry (n = 62), and serum protein electrophoresis (n = 32) in physically
      restrained free-ranging roe deer (Capreolus capreolus). Animals were captured in
      box traps and physically restrained for blood sampling during the winter in
      Sweden, 2011-13. No clinically significant sex or age differences were found.

PMID- 25375950
TI  - Chlamydia psittaci in Eurasian Collared Doves (Streptopelia decaocto) in Italy.
AB  - We investigated the Chlamydia spp. occurrence in Eurasian Collared Doves
      (Streptopelia decaocto) from urban and suburban areas in northern Italy. Among 76
      doves screened, prevalence of Chlamydia spp. was 61%. Chlamydia psittaci genotype
      E was identified in 33 of the 46 positive samples. The multilocus sequence typing
      pattern of one highly positive sample showed a new allelic combination. The same
      molecular features were observed in a C. psittaci strain subsequently isolated
      from a live dove. Our results reveal a high C. psittaci prevalence in S.
      decaocto. The spread of this zoonotic pathogen from collared doves to other birds
      or humans seems to be a potential risk.

PMID- 25375952
TI  - Combined effects of turbulence and different predation regimes on zooplankton in
      highly colored water-implications for environmental change in lakes.
AB  - In aquatic ecosystems, predation is affected both by turbulence and visibility,
      but the combined effects are poorly known. Both factors are changing in lakes in
      the Northern Hemisphere; the average levels of turbulence are predicted to
      increase due to increasing wind activities, while water transparency is
      decreasing, e.g., due to variations in precipitation, and sediment resuspension.
      We explored experimentally how turbulence influenced the effects of planktivorous
      fish and invertebrate predators on zooplankton when it was combined with low
      visibility caused by high levels of water color. The study was conducted as a
      factorial design in 24 outdoor ponds, using the natural zooplankton community as
      a prey population. Perch and roach were used as vertebrate predators and
      Chaoborus flavicans larvae as invertebrate predators. In addition to calm
      conditions, the turbulent dissipation rate used in the experiments was 10-6 m2 s
      3, and the water color was 140 mg Pt L-1. The results demonstrated that in a
      system dominated by invertebrates, predation pressure on cladocerans increased
      considerably under intermediate turbulence. Under calm conditions, chaoborids
      caused only a minor reduction in the crustacean biomass. The effect of fish
      predation on cladocerans was slightly reduced by turbulence, while predation on
      cyclopoids was strongly enhanced. Surprisingly, under turbulent conditions fish
      reduced cyclopoid biomass, whereas in calm water it increased in the presence of
      fish. We thus concluded that turbulence affects fish selectivity. The results
      suggested that in dystrophic invertebrate-dominated lakes, turbulence may
      severely affect the abundance of cladocerans. In fish-dominated dystrophic lakes,
      on the other hand, turbulence-induced changes in planktivory may considerably
      affect copepods instead of cladocerans. In lakes inhabited by both invertebrates
      and fish, the response of top-down regulation to turbulence resembles that in
      fish-dominated systems, due to intraguild predation. The changes in planktivorous
      predation induced by abiotic factors may possibly cascade to primary producers. 

PMID- 25375951
TI  - Oral shedding of Marburg virus in experimentally infected Egyptian fruit bats
      (Rousettus aegyptiacus).
AB  - Marburg virus (Marburg marburgvirus; MARV) causes sporadic outbreaks of Marburg
      hemorrhagic fever (MHF) in Africa. The Egyptian fruit bat (Rousettus aegyptiacus)
      has been identified as a natural reservoir based most-recently on the repeated
      isolation of MARV directly from bats caught at two locations in southwestern
      Uganda where miners and tourists separately contracted MHF from 2007-08. Despite
      learning much about the ecology of MARV through extensive field investigations,
      there remained unanswered questions such as determining the primary routes of
      virus shedding and the severity of disease, if any, caused by MARV in infected
      bats. To answer these questions and others, we experimentally infected captive
      bred R. aegyptiacus with MARV under high (biosafety level 4) containment. These
      experiments have shown infection profiles consistent with R. aegyptiacus being a
      bona fide natural reservoir host for MARV and demonstrated routes of viral
      shedding capable of infecting humans and other animals.

PMID- 25375953
TI  - Inhibitors of peptidyl proline isomerases as antivirals in hepatitis C and other
      viruses.

PMID- 25375954
TI  - Recent advances in optical imaging with anisotropic plasmonic nanoparticles.

PMID- 25375955
TI  - Hospital discharges, readmissions, and ED visits for COPD or bronchiectasis among
      US adults: findings from the nationwide inpatient sample 2001-2012 and Nationwide
      Emergency Department Sample 2006-2011.
AB  - BACKGROUND: Numbers and rates of hospitalizations and ED visits by patients with
      COPD are important metrics for surveillance purposes. The objective of this study
      was to examine trends in these rates from 2001 to 2012 among adults aged >= 18
      years in the United States. METHODS: Data from the Nationwide Inpatient Sample
      (NIS) and Nationwide Emergency Department Sample (NEDS) were examined for
      temporal trends in the numbers and rates of hospitalizations by patients with
      COPD or bronchiectasis, mean length of stay, in-hospital case-fatality rate, 30
      day readmission rate, and numbers and rates of ED visits. RESULTS: The national
      number of discharges with COPD or bronchiectasis as the principal diagnosis was
      about 88,000 higher in 2012 than in 2001, but the age-adjusted rate of discharges
      did not change significantly (range, 242.7-286.0 per 100,000 population, P trend
      = .554). In contrast, hospitalization rates for common cardiovascular disorders,
      pneumonia, and lung cancer decreased significantly by 27% to 68%, whereas the
      mean charge doubled and mean cost increased by 40%. From 2006 to 2011, the
      numbers of ED visits increased from 1,480,363 to 1,787,612. The age-adjusted rate
      increased nonsignificantly from 654 to 725 per 100,000 population (P trend =
      .072). CONCLUSIONS: Despite many local and national efforts to reduce the burden
      of COPD, total hospitalizations and ED visits over the past decade have increased
      for COPD, and the age-adjusted rates of hospitalizations and ED visits for COPD
      or bronchiectasis have not changed significantly in the United States.

PMID- 25375956
TI  - Anesthesia Management in Aortic Dissection in Patients Undergoing Kidney
      Transplant.
AB  - Kidney transplant is a last resort to increase the life expectancy and quality of
      life in patients with renal failure. Aortic dissection is a disease that requires
      emergency intervention; it is characterized by sudden life-threatening back or
      abdominal pain. In the case described, constant chest pain that increased with
      respiration was present on examination of a 28-year-old man (85 kg, 173 cm) who
      presented at our emergency department complaining of severe back pain. He had
      undergone a kidney transplant in 2004 from his mother (live donor). He was
      diagnosed with acute Type II aortic dissection and was scheduled for emergent
      surgery. Because there were no surgical or anesthetic complications, the patient
      with 79 and 89 minutes aortic cross-clamping and cardiopulmonary bypass durations
      was sent, intubated, to intensive care unit. When nephrotoxic agents are avoided
      and blood flow is stabilized, cardiovascular surgery with cardio-pulmonary bypass
      may be performed seamlessly in patients who have undergone a kidney transplant.

PMID- 25375958
TI  - Observation of the inverse giant piezoresistance effect in silicon nanomembranes
      probed by ultrafast terahertz spectroscopy.
AB  - The anomalous piezoresistance (a-PZR) effects, including giant PZR (GPZR) with
      large magnitude and inverse PZR of opposite, have exciting technological
      potentials for their integration into novel nanoelectromechanical systems.
      However, the nature of a-PZR effect and the associated kinetics have not been
      clearly determined yet. Even further, there are intense research debates whether
      the a-PZR effect actually exists or not; although numerous investigations have
      been conducted, the origin of the effect has not been clearly understood. This
      paper shows the existence of a-PZR and provides direct experimental evidence
      through the performance of well-established electrical measurements and terahertz
      spectroscopy on silicon nanomembranes (Si NMs). The clear inverse PZR behavior
      was observed in the Si NMs when the thickness was less than 40 nm and the
      magnitude of the PZR response linearly increased with the decreasing thickness.
      Observations combined with electrical and optical measurements strongly
      corroborate that the a-PZR effect originates from the carrier concentration
      changes via charge carrier trapping into strain-induced defect states. 

PMID- 25375957
TI  - Localizing movement-related primary sensorimotor cortices with multi-band EEG
      frequency changes and functional MRI.
AB  - Electroencephalographic (EEG) oscillations in multiple frequency bands can be
      observed during functional activity of the cerebral cortex. An important question
      is whether activity of focal areas of cortex, such as during finger movements, is
      tracked by focal oscillatory EEG changes. Although a number of studies have
      compared EEG changes to functional MRI hemodynamic responses, we can find no
      previous research that relates the fMRI hemodynamic activity to localization of
      the multiple EEG frequency changes observed in motor tasks. In the present study,
      five participants performed similar thumb and finger movement tasks in parallel
      EEG and functional MRI studies. We examined changes in five frequency bands (from
      5-120 Hz) and localized them using 256 dense-array EEG (dEEG) recordings and high
      resolution individual head models. These localizations were compared with fMRI
      localizations in the same participants. Results showed that beta-band (14-30 Hz)
      desynchronizations (power decreases) were the most robust effects, appearing in
      all individuals, consistently localized to the hand region of the primary motor
      cortex, and consistently aligned with fMRI localizations. 

PMID- 25375959
TI  - Reperfusion of areas of ischemia in central retinal vein occlusion.

PMID- 25375960
TI  - Seroprevalence and determinants of Kaposi sarcoma-associated human herpesvirus 8
      in Indian HIV-infected males.
AB  - In India Kaposi's sarcoma is rarely seen in AIDS patients. Hence the current
      belief is that the incidence of human herpesvirus-8 (HHV-8) is very low in this
      subcontinent, most probably due to the heterosexual route of HIV transmission.
      However, there is a scarcity of data on the prevalence of HHV-8 in India. In
      India the primary mode of HIV transmission is the heterosexual route. Therefore
      we aimed to determine the prevalence of antibodies against HHV-8 in North Indian
      HIV-infected men naive of antiretroviral therapy (ART). In a prospective study,
      165 Indian adult males were recruited from an ART clinic. Blood samples were
      collected before administering any antiretroviral drug. The sera were tested for
      antibodies against HHV-8 using a commercial enzyme-linked immunosorbent assay
      (ELISA) kit, which detects IgG antibodies to lytic antigens of HHV-8. All
      positive samples were confirmed for the presence of anti-HHV-8 antibodies using
      an indirect immunofluorescence assay (IFA). The IFA kit is intended to detect
      primary, latent, persistent, or reactivated infection of HHV-8. Of the 165 males,
      43 (26.06%) were positive by ELISA while 26 (15.8%) were also positive by IFA.
      Seroprevalence decreased with increasing age (p<0.05). Factors independently
      associated with HHV-8 infection were younger age group and alcohol consumption.
      These findings suggest that even in a heterosexual population, HHV-8 can be
      transmitted frequently.

PMID- 25375961
TI  - Tunable-color luminescence via energy transfer in NaCa13/18Mg5/18PO4:A (A =
      Eu2+/Tb3+/Mn2+, Dy3+) phosphors for solid state lighting.
AB  - A series of NaCa13/18Mg5/18PO4(NCMPO):A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+))
      phosphors have been prepared by the high-temperature solid-state reaction method.
      The X-ray diffraction (XRD) and Rietveld refinement, X-ray photoelectron
      spectroscopy (XPS), photoluminescence (PL), cathodoluminescence (CL), decay
      lifetimes, and PL quantum yields (QYs) were utilized to characterize the
      phosphors. The pure crystalline phase of as-prepared samples has been
      demonstrated via XRD measurement and Rietveld refinements. XPS reveals that the
      Eu(2+)/Tb(3+)/Mn(2+) can be efficiently doped into the crystal lattice.
      NCMPO:Eu(2+)/Tb(3+)/Mn(2+) phosphors can be effectively excited under UV
      radiation, which show tunable color from purple-blue to red including white
      emission based on energy transfer from Eu(2+) to Tb(3+)/Mn(2+) ions. Under low
      voltage electron beam bombardment, the NCMPO:A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+))
      display their, respectively, characteristic emissions with different colors, and
      the CL spectrum of NCMPO:0.04Tb(3+) has the comparable intensity to the ZnO:Zn
      commercial product. In addition, the calculated CIE coordinate of
      NCMPO:0.04Tb(3+) (0.252, 0.432) is more saturated than it (0.195, 0.417). These
      results reveal that NCMPO:A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) may be potential
      candidate phosphors for WLEDs and FEDs. 

PMID- 25375963
TI  - Entropy-enthalpy compensation at the single protein level: pH sensing in the
      bacterial channel OmpF.
AB  - The pH sensing mechanism of the OmpF channel operates via ligand modification:
      increasing acidity induces the replacement of cations with protons in critical
      binding sites decreasing the channel conductance. Aside from the change in
      enthalpy associated with the binding, there is also a change in the microscopic
      arrangements of ligands, receptors and the surrounding solvent. We show that the
      pH-modulation of the single channel conduction involves small free energy changes
      because large enthalpic and entropic contributions change in opposite ways,
      demonstrating an approximate enthalpy-entropy compensation for different salts
      and concentrations. 

PMID- 25375964
TI  - Relationship of pulse pressure index and carotid intima-media thickness in
      hypertensive adults.
AB  - OBJECTIVE: To evaluate the relationship between pulse pressure index (PPI) and
      carotid intima-media thickness (CIMT). METHOD: Observational trial was design and
      342 patients newly diagnosed as hypertension without anti-hypertensive therapy
      were enrolled. According to the cut-off value of CIMT, 342 participants were
      divided into normal (< 0.9mm) and increased CIMT groups (>= 0.9mm). Baseline
      characteristics were compared, logistic regression analysis and receiver
      operating characteristic curve (ROC) were performed. RESULTS: Approximately 34.2%
      of participants (n = 117) were with CIMT >= 0.9 mm and participants in increased
      CIMT group were more elderly. Diastolic blood pressure was lower in increased
      CIMT group than normal group (79.3 +/- 10.8 mm Hg versus 83.8 +/- 9.4 mm Hg, p <
      0.001), whereas pulse pressure (PP) (59.3 +/- 20.2 mm Hg versus 53.6 +/- 15.5 mm
      Hg, p = 0.004) and PPI (0.43 +/- 0.09 versus 0.38 +/- 0.08, p < 0.001) were
      significantly higher in increased CIMT group. CIMTs were 1.11 +/- 0.11 mm and
      0.76 +/- 0.12 in increased group and normal group respectively (p < 0.001). After
      adjusted for the traditional risk factors, only PPI was found an independent
      determinant for CIMT increase, and the odd ratio was 1.644 (95% interval
      confidence 1.280-2.112, p < 0.001). The ROC evaluations showed that area under
      the curve for PP to predict CIMT increase was 0.591 +/- 0.034, and PPI was 0.664
      +/- 0.033. PPI was more powerful than PP in discriminating CIMT increase (p =
      0.006). CONCLUSION: PPI is a valuable parameter for the preliminary screening of
      hypertensive patients who have an increased risk of atherosclerosis.

PMID- 25375965
TI  - A new patient-controlled technique for shoulder relocation in emergency
      departments.
AB  - BACKGROUND: The glenohumeral joint is the most mobile joint in the human body due
      to the shallowness of the glenoid socket. This unique anatomy also makes it the
      most dislocated joint in humans. All the techniques described so far for
      relocation require operator control and prescription drugs. We describe a
      technique that is unique, easy, and patient-controlled. CASE REPORT: A 29-year
      old male patient presented to the Emergency Department after falling from
      scaffolding at work. He had left shoulder dislocation confirmed by clinical and
      radiological examination. The patient lay face down on the trolley with trolley
      being raised with electronic controls. The shoulder was reduced with ease and the
      patient was discharged home after radiologic confirmation of reduction.
      CONCLUSIONS: A new patient-controlled technique for reduction of the glenohumeral
      joint following dislocation is described. It is simple, safe, and effective to
      perform in Emergency Departments.

PMID- 25375966
TI  - On the origin of fluorescence emission in optically non-linear DCNP crystals.
AB  - We study absorption and emission spectra of optically nonlinear single crystals
      of 3-(1,1-dicyanoethenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (DCNP) at 5 K. We
      argue that fluorescence has a complex origin, it is emitted from the excitonic
      band, with the bottom at ~18,115 cm(-1), and from trap states, and the two main
      traps have depths of ~875 and ~2465 cm(-1). The excitonic origin of the emission
      is confirmed by the vibrational structure of fluorescence, closely resembling
      vibrations observed in the Raman scattering spectrum (recorded for DCNP crystals
      at 295 K) and by very short decay time of the excitonic emission, as a
      consequence of exciton migration and trapping at deep traps.

PMID- 25375967
TI  - In memoriam: Mary G. Enig, PhD, MACN.

PMID- 25375969
TI  - Experimental study of thermal stability of thin nanowires.
AB  - Thin (D < 10 nm) nanowires are in principle promising for their application as
      catalysts and as elements of nanocomputers and quantum devices. To perform these
      tasks, their structure and properties must be stable at least at standard
      conditions. Using our technique based on the capture of small particles to the
      core of quantized vortices in superfluid helium, we synthesized nanowires made of
      various metals and alloys and investigated their thermal stability. The indium
      nanowires (D = 8 nm) were shown to be stable when heated to 100  degrees C, i.e.,
      almost to the melting point, whereas the silver nanowires (D = 5 nm)
      disintegrated into traces of individual nanoclusters at 300 K. The gold and
      platinum nanowires also decomposed at temperatures more than twice as low as the
      melting point. A model is proposed to explain the premature decay of thin
      nanowires by unfreezing of the surface-atom mobility in combination with the
      anomalous dependence of the surface tension on the nanowire radius. Methods for
      improving the stability limits of thin nanowires by saturation of their surface
      with immobilized atoms as well as by surface oxidation have been proposed and
      experimentally tested. 

PMID- 25375970
TI  - Droplet coalescence on water repellant surfaces.
AB  - We report our hydrodynamic and energy analyses of droplet coalescence on water
      repellent surfaces including hydrophobic, superhydrophobic and oil-infused
      superhydrophobic surfaces. The receding contact angle has significant effects on
      the contact line dynamics since the contact line dissipation was more significant
      during the receding mode than advancing. The contact line dynamics is modeled by
      the damped harmonic oscillation equation, which shows that the damping ratio and
      angular frequency of merged droplets decrease as the receding contact angle
      increases. The fast contact line relaxation and the resulting decrease in base
      area during coalescence were crucial to enhance the mobility of coalescing
      sessile droplets by releasing more surface energy with reducing dissipation loss.
      The superhydrophobic surface converts ~42% of the released surface energy to the
      kinetic energy via coalescence before the merged droplet jumps away from the
      surface, while oil-infused superhydrophobic and hydrophobic surfaces convert ~30%
      and ~22%, respectively, for the corresponding time. This work clarifies the
      mechanisms of the contact line relaxation and energy conversion during the
      droplet coalescence on water repellent surfaces, and helps develop water
      repellent condensers. 

PMID- 25375971
TI  - Physical aggression and language ability from 17 to 72 months: cross-lagged
      effects in a population sample.
AB  - BACKGROUND: Does poor language ability in early childhood increase the likelihood
      of physical aggression or is language ability delayed by frequent physical
      aggression? This study examined the longitudinal associations between physical
      aggression and language ability from toddlerhood to early childhood in a
      population sample while controlling for parenting behaviours, non-verbal
      intellectual functioning, and children's sex. METHODS: Children enrolled in the
      Quebec Longitudinal Study of Child Development (QLSCD) (N = 2, 057) were assessed
      longitudinally from 17 to 72 months via parent reports and standardized
      assessments. RESULTS: The cross-lagged models revealed modest reciprocal
      associations between physical aggression and language performance from 17 to 41
      months but not thereafter. CONCLUSIONS: Significant associations between physical
      aggression and poor language ability are minimal and limited to the period when
      physical aggression and language performance are both substantially increasing.
      During that period parenting behaviours may play an important role in supporting
      language ability while reducing the frequency of physical aggression. Further
      studies are needed that utilize multiple assessments of physical aggression,
      assess multiple domains of language abilities, and that examine the potential
      mediating role of parenting behaviours between 12 and 48 months.

PMID- 25375972
TI  - Unhealthy Body Weight, Illness Absence, Presenteeism, Medical Payments, and
      Disability Leave: A Longitudinal View.
AB  - The objective of this study is to examine how much of the relationships between
      unhealthy body weight, and health and productivity outcomes are attributable to
      health status, and how much can be ameliorated by weight loss or improvements in
      health. Cross-sectional and first-difference regressions were conducted of
      employees' body mass index (BMI) category, illness absences, presenteeism,
      medical spending, and disability leaves. Employees in the obese BMI category have
      significantly worse outcomes than employees in the healthy and overweight BMI
      categories. Controlling for physical and emotional health status mediates much of
      the observed relationships. Improved health, stress, and psychological distress
      are associated with reduced illness absence and presenteeism among overweight and
      obese employees. Obese employees who lost weight experienced reduced
      presenteeism. The findings suggest that overweight and obese employees can
      realize improved productivity without weight loss.

PMID- 25375973
TI  - Enhancement of lipid productivity in oleaginous Colletotrichum fungus through
      genetic transformation using the yeast CtDGAT2b gene under model-optimized growth
      condition.
AB  - Oleaginous fungi are of special interest among microorganisms for the production
      of lipid feedstocks as they can be cultured on a variety of substrates,
      particularly waste lingocellulosic materials, and few fungal strains are reported
      to accumulate inherently higher neutral lipid than bacteria or microalgae.
      Previously, we have characterized an endophytic filamentous fungus Colletotrichum
      sp. DM06 that can produce total lipid ranging from 34% to 49% of its dry cell
      weight (DCW) upon growing with various carbon sources and nutrient-stress
      conditions. In the present study, we report on the genetic transformation of this
      fungal strain with the CtDGAT2b gene, which encodes for a catalytically efficient
      isozyme of type-2 diacylglycerol acyltransferase (DGAT) from oleaginous yeast
      Candida troplicalis SY005. Besides the increase in size of lipid bodies, total
      lipid titer by the transformed Colletotrichum (lipid content ~73% DCW) was found
      to be ~1.7-fold more than the wild type (lipid content ~38% DCW) due to
      functional activity of the CtDGAT2b transgene when grown under standard condition
      of growth without imposition of any nutrient-stress. Analysis of lipid
      fractionation revealed that the neutral lipid titer in transformants increased up
      to 1.8-, 1.6- and 1.5-fold compared to the wild type when grown under standard,
      nitrogen stress and phosphorus stress conditions, respectively. Lipid titer of
      transformed cells was further increased to 1.7-fold following model-based
      optimization of culture conditions. Taken together, ~2.9-fold higher lipid titer
      was achieved in Colletotrichum fungus due to overexpression of a rate-limiting
      crucial enzyme of lipid biosynthesis coupled with prediction-based bioprocess
      optimization. 

PMID- 25375974
TI  - Double-headed nucleotides with arabino configuration: synthesis and hybridization
      properties.
AB  - The formation of new nucleic acid motifs by using double-headed nucleotides is
      reported. Modified phosphoramidites carrying additional thymine or adenine
      attached to the 2'-position of arabinouridine through a methylene linker are
      conveniently prepared and incorporated into oligonucleotides to obtain the
      modified nucleotide monomers (a)U(T) and (a)U(A), respectively. The extension of
      a DNA double helix by one or two additional A:T base pairs is achieved by placing
      these modified monomers in the opposite strands in a so-called (+1)-zipper
      arrangement. Hence, 12 basepairs can be presented in an 11-mer or even a 10-mer
      duplex. The modified nucleotide monomers also behave as dinucleotides when base
      paired with two complementary nucleotides from the opposite strand. A new nucleic
      acid motif is introduced when two (a)U(A) monomers recognize each other in the
      center of a duplex.

PMID- 25375975
TI  - The new explorations of the neurorestorative process: a brief introduction to the
      IANR special issue.

PMID- 25375976
TI  - Formation of G-quadruplexes in poly-G sequences: structure of a propeller-type
      parallel-stranded G-quadruplex formed by a G15 stretch.
AB  - Poly-G sequences are found in different genomes including human and have the
      potential to form higher-order structures with various applications. Previously,
      long poly-G sequences were thought to lead to multiple possible ways of G
      quadruplex folding, rendering their structural characterization challenging. Here
      we investigate the structure of G-quadruplexes formed by poly-G sequences
      d(TTG(n)T), where n = 12 to 19. Our data show the presence of multiple and/or
      higher-order G-quadruplex structures in most sequences. Strikingly, NMR spectra
      of the TTG15T sequence containing a stretch of 15 continuous guanines are
      exceptionally well-resolved and indicate the formation of a well-defined G
      quadruplex structure. The NMR solution structure of this sequence revealed a
      propeller-type parallel-stranded G-quadruplex containing three G-tetrad layers
      and three single-guanine propeller loops. The same structure can potentially form
      anywhere along a long G(n) stretch, making it unique for molecular recognition by
      other cellular molecules.

PMID- 25375977
TI  - Toxoplasmosis seroprevalence in wild small rodents, potentially preys of ocelots
      in north-eastern Mexico.
AB  - The aim of this study was to assess the prevalence of Toxoplasma gondii infection
      in rodents that coexist with ocelots in north-eastern Mexico. Eighty rodents of
      five genera were captured and their serum samples tested for specific IgG
      antibodies to T. gondii by in-house indirect ELISA using three different
      conjugates. Prevalences of 7% (3/44) and 33% (4/12) were found in Sigmodon
      hispidus and Liomys irroratus, respectively, and were significantly different.
      All Baiomys taylori and Oligoryzomys fulvescens were negative for the presence of
      anti-T. gondii IgG antibodies. The samples from Peromyscus spp. could not be
      analyzed because none of the three conjugates tested recognized their
      immunoglobulins. Infection was confirmed in one single specimen of L. irroratus
      by qPCR, which generated an estimate of 146 parasites per mg of muscle tissue.
      The results strongly support the notion of active T. gondii transmission between
      rodents and felines in this zone of Mexico and an important role of some rodent
      species in the sylvatic cycle of T. gondii. 

PMID- 25375978
TI  - gamma-Butyrolactone, cytochalasin, cyclic carbonate, eutypinic acid, and
      phenalenone derivatives from the soil fungus Aspergillus sp. PSU-RSPG185.
AB  - Purification of an extract from the broth of the soil fungus Aspergillus sp. PSU
      RSPG185 resulted in the isolation of two new cyclic carbonate derivatives,
      aspergillusols A (1) and B (2), and one new eutypinic acid derivative,
      aspergillusic acid (3), along with six known secondary metabolites. Compounds 1
      and 2 contain an unusual cyclic-carbonate functionality. In addition, the
      mycelial extract afforded two new phenalenones, aspergillussanones A (4) and B
      (5), one new cytochalasin, aspergilluchalasin (6), and one new gamma
      butyrolactone, aspergillulactone (7). Their structures were established by
      interpretation of spectroscopic evidence. Compound 4 exhibited weak activity
      toward KB and Vero cells with IC50 values of 48.4 and 34.2 MUM, respectively. 

PMID- 25375979
TI  - Intact pituitary function is decisive for the catabolic response to TNF-alpha:
      studies of protein, glucose and fatty acid metabolism in hypopituitary and
      healthy subjects.
AB  - CONTEXT: TNF-alpha generates inflammatory responses and insulin resistance,
      lipolysis, and protein breakdown. It is unclear whether these changes depend on
      intact hypothalamo-pituitary stress hormone responses to trigger the release of
      cortisol and growth hormone. OBJECTIVE: To define differential effects of TNF
      alpha on glucose, protein, and lipid metabolism in hypopituitary patients
      (without intact hypothalamo-pituitary axis) and healthy controls. DESIGN:
      Randomized, placebo controlled, single-blinded. Setting, Participants, and
      Intervention: We studied eight hypopituitary (HP) patients and eight matched
      control subjects [control volunteers (CTR)] twice during 4-h basal and 2-h
      hyperinsulinemic clamp conditions with isotope dilution during infusion of saline
      or TNF-alpha(12 ng/kg/h) for 6 h. MAIN OUTCOME MEASURES: Phenylalanine, urea,
      palmitate, and glucose fluxes and fat biopsies in basal and clamp periods.
      RESULTS: TNF-alpha infusion significantly increased cortisol and GH levels in CTR
      but not in HP. TNF-alpha increased phenylalanine fluxes in both groups, with the
      increase being significantly greater in CTR, and raised urea flux by 40 % in CTR
      without any alteration in HP. Endogenous glucose production (EGP) was elevated in
      CTR compared to HP after TNF-alpha administration, whereas insulin sensitivity
      remained similarly unaffected in both groups. TNF-alpha increased whole body
      palmitate fluxes and decreased palmitate specific activity in CTR, but not in HP
      without statistical difference between groups. We did not detect significant
      effects TNF-alpha on lipase expression or regulation in fat. CONCLUSIONS: TNF
      alpha increased both urea and amino acid fluxes and EGP significantly more in CTR
      compared to HP, suggesting that increases in endogenous cortisol and GH release
      are significant components of the metabolic response to TNF-alpha.

PMID- 25375980
TI  - Diagnosis of diabetes mellitus using HbA1c in Asians: relationship between HbA1c
      and retinopathy in a multiethnic Asian population.
AB  - CONTEXT: Hemoglobin A1c (HbA1c) >= 6.5% (47.5 mmol/mol) has recently been
      included as a criterion for the diagnosis of diabetes mellitus. It is unclear
      whether this criterion is appropriate in Asians. OBJECTIVE: To examine the
      relationship between HbA1c and diabetes-specific moderate retinopathy in Asian
      ethnic groups. DESIGN, SETTING, AND PARTICIPANTS: Four independent population
      based cross-sectional studies (2004-2011) in Singapore representing the three
      major Asian ethnic groups (n = 13 170 adults aged >= 25 y: Chinese, 5834; Malays,
      3596; and Indians, 3740). MAIN OUTCOME: Moderate retinopathy was assessed from
      digital retinal photographs and defined as a level >43 using the Early Treatment
      Diabetic Retinopathy Study (ETDRS) scale. Sensitivity, specificity, positive and
      negative predictive values, and the area under the receiver operating
      characteristic curve for detecting moderate retinopathy were compared across
      ethnic groups at different HbA1c cut-points. RESULTS: HbA1c levels were higher in
      Indians and Malays compared to Chinese (P < .001). The prevalence of moderate
      retinopathy below HbA1c <6.5% was <1% in all ethnic groups. At HbA1c >= 6.5%, the
      sensitivity for detecting moderate retinopathy was lower in Chinese subjects
      compared to Indians and Malays (75.8 vs 86.0 and 85.3%), but specificity (89.7 vs
      71.9 and 76.3%) was higher; however, positive predictive value and negative
      predictive value were similar among Chinese, Indians, and Malays (10.5, 12.3,
      12.4%; and 99.6, 99.1, 99.2%, respectively). The AUCs were similar across all
      three ethnic groups (0.861, 0.851, and 0.853). CONCLUSIONS: Our study supports
      the use of HbA1c for diagnosing diabetes in Asians. Despite some interethnic
      variation in the relationship of HbA1c and retinopathy, a cut-point of 6.5%
      performs reasonably well in the three major Asian ethnic groups.

PMID- 25375981
TI  - Rationale for the application of RANKL inhibition in the treatment of Langerhans
      cell histiocytosis.
AB  - CONTEXT: Langerhans Cell Histiocytosis (LCH) is a rare disease exhibiting both
      neoplastic and inflammatory features including abundant cytokine secretion both
      at the lesional and systemic level. OBJECTIVE: Evaluation of RANKL expression
      within LCH lesions in various tissues. DESIGN: Cross-sectional study involving
      paraffin blocks from the diagnostic biopsies of adults with LCH. SETTING: The
      study was conducted among patients followed in an adult outpatient clinic.
      SUBJECTS: Eleven patients with active LCH, who were 41.27 +/- 3.44 years old, and
      five patients who were 46.8 +/- 7.19 years old with non-LCH diagnosis serving as
      controls. INTERVENTIONS: RANKL, p65 and CD1a immunostaining of deparaffinized
      sections from LCH lesions and control tissues. MAIN OUTCOME MEASURE: Comparison
      of RANKL and p65 expression between LCH lesions, as indicated from concomitant
      CD1a immunostaining, and control tissue counterparts. RESULTS: A focal positive
      granular cytoplasmic RANKL staining was found at all lesional sites in a number
      of cells of the pathological infiltrate, mostly with morphologic features of
      pathological Langerhans cells (LCs). Compared to control tissues, RANKL
      positivity in LCH cases showed an excess of staining, both in intensity of
      staining and the number of stained cells, especially in areas of pathologic
      infiltration. RANKL staining also coincided with strong p65 NFkappaB nuclear
      positivity, especially in lesional infiltrates. CONCLUSIONS: RANKL is highly
      expressed in active LCH at the lesional level, concomitant to p65 NFkappaB
      activation. The use of RANKL inhibition as a rational therapeutic approach of the
      disease now needs further clinical evaluation.

PMID- 25375982
TI  - Relationship between serum IGF-1 and skeletal muscle IGF-1 mRNA expression to
      phosphocreatine recovery after exercise in obese men with reduced GH.
AB  - CONTEXT: GH and IGF-1 are believed to be physiological regulators of skeletal
      muscle mitochondria. OBJECTIVE: The objective of this study was to examine the
      relationship between GH/IGF-1 and skeletal muscle mitochondria in obese subjects
      with reduced GH secretion in more detail. DESIGN: Fifteen abdominally obese men
      with reduced GH secretion were treated for 12 weeks with recombinant human GH.
      Subjects underwent (31)P-magnetic resonance spectroscopy to assess
      phosphocreatine (PCr) recovery as an in vivo measure of skeletal muscle
      mitochondrial function and percutaneous muscle biopsies to assess mRNA expression
      of IGF-1 and mitochondrial-related genes at baseline and 12 weeks. RESULTS: At
      baseline, skeletal muscle IGF-1 mRNA expression was significantly associated with
      PCr recovery (r = 0.79; P = .01) and nuclear respiratory factor-1 (r = 0.87; P =
      .001), mitochondrial transcription factor A (r = 0.86; P = .001), peroxisome
      proliferator-activated receptor (PPAR)gamma (r = 0.72; P = .02), and PPARalpha (r
      = 0.75; P = .01) mRNA expression, and trended to an association with PPARgamma
      coactivator 1-alpha (r = 0.59; P = .07) mRNA expression. However, serum IGF-1
      concentration was not associated with PCr recovery or any mitochondrial gene
      expression (all P > .10). Administration of recombinant human GH increased both
      serum IGF-1 (change, 218 +/- 29 MUg/L; P < .0001) and IGF-1 mRNA in muscle (fold
      change, 2.1 +/- 0.3; P = .002). Increases in serum IGF-1 were associated with
      improvements in total body fat (r = -0.53; P = .04), trunk fat (r = -0.55; P =
      .03), and lean mass (r = 0.58; P = .02), but not with PCr recovery (P > .10).
      Conversely, increase in muscle IGF-1 mRNA was associated with improvements in PCr
      recovery (r = 0.74; P = .02), but not with body composition parameters (P > .10).
      CONCLUSION: These data demonstrate a novel association of skeletal muscle
      mitochondria with muscle IGF-1 mRNA expression, but independent of serum IGF-1
      concentrations.

PMID- 25375983
TI  - Incretin and islet hormone responses to meals of increasing size in healthy
      subjects.
AB  - CONTEXT: Postprandial glucose homeostasis is regulated through the secretion of
      glucagon-like peptide 1 (GLP-1) through the stimulation of insulin secretion and
      inhibition of glucagon secretion. However, how these processes dynamically adapt
      to demands created by caloric challenges achieved during daily life is not known.
      OBJECTIVE: The objective of the study was to explore the adaptation of incretin
      and islet hormones after mixed meals of increasing size in healthy subjects.
      DESIGN: Twenty-four healthy lean subjects ingested a standard breakfast after an
      overnight fast followed, after 4 hours, by a lunch of a different size (511, 743,
      and 1034 kcal) but with identical nutrient composition together with 1.5 g
      paracetamol. Glucose, insulin, C-peptide, glucagon, intact GLP-1, and glucose
      dependent insulinotropic polypeptide (GIP) and paracetamol were measured after
      the meals. MAIN OUTCOME MEASURE: Area under the 180-minute curve (AUC) for
      insulin, C-peptide, glucagon, GLP-1, and GIP and model-derived beta-cell function
      and paracetamol appearance were calculated. RESULTS: Glucose profiles were
      similar after the two larger meals, whereas after the smaller meal, there was a
      postpeak reduction below baseline to a nadir of 3.8 +/- 0.1 mmol/L after 75
      minutes (P < .001). The AUC for GLP-1, GIP, insulin, and C-peptide were
      significantly higher by increasing the caloric load as was beta-cell sensitivity
      to glucose. In contrast, the AUC glucagon was the same for all three meals,
      although there was an increase in glucagon after the postpeak glucose reduction
      in the smaller meal. The 0- to 20-minute paracetamol appearance was increased by
      increasing meal size. CONCLUSION: Mixed lunch meals of increasing size elicit a
      caloric-dependent insulin response due to increased beta-cell secretion achieved
      by increased GIP and GLP-1 levels. The adaptation at larger meals results in
      identical glucose excursions, whereas after a lower caloric lunch, the insulin
      response is high, resulting in a postpeak suppression of glucose below baseline.

PMID- 25375984
TI  - Clinical review: Thyroid cancer mimics on surveillance neck sonography.
AB  - Sonography of the neck is a critical tool in monitoring patients after near-total
      thyroidectomy for differentiated thyroid cancer. Sonography has proven to be
      among the most sensitive imaging techniques for the detection of recurrent or
      residual cancer in the thyroidectomy bed and metastatic cervical lymph nodes. It
      is important for the sonologist to be familiar with normal postsurgical findings
      and other disease processes that may imitate malignant lesions. We describe the
      typical sonographic appearance of benign lesions that can resemble recurrent
      thyroid cancer. 

PMID- 25375985
TI  - A review: Radiographic iodinated contrast media-induced thyroid dysfunction.
AB  - CONTEXT: Thyroid hormone production is dependent on adequate iodine intake.
      Excess iodine is generally well-tolerated, but thyroid dysfunction can occur in
      susceptible individuals after excess iodine exposure. Radiological iodinated
      contrast media represent an increasingly common source of excess iodine.
      OBJECTIVE: This review will discuss the thyroidal response after acute exposure
      to excess iodine; contrast iodine-induced thyroid dysfunction; risks of iodine
      induced thyroid dysfunction in vulnerable populations, such as the fetus,
      neonate, and patients with impaired renal function; and recommendations for the
      assessment and treatment of contrast iodine-induced thyroid dysfunction. METHODS:
      Data for this review were identified by searching PubMed, Google Scholar, and
      references from relevant articles from 1948 to 2014. CONCLUSIONS: With the
      increase in the use of computed tomography scans in the United States, there is
      increasing risk of contrast-induced thyroid dysfunction. Patients at risk of
      developing iodine-induced thyroid dysfunction should be closely monitored after
      receiving iodinated contrast media and should be treated as needed.

PMID- 25375987
TI  - Excess mortality and morbidity in patients with craniopharyngioma, especially in
      patients with childhood onset: a population-based study in Sweden.
AB  - CONTEXT: Craniopharyngiomas (CPs) in adults have been associated with excess
      mortality. OBJECTIVE: The aim of the study was to investigate mortality and
      morbidity in patients with childhood-onset and adult-onset CP. METHODS: PATIENTS
      with CP were identified and followed in Swedish national health registries, 1987
      through 2011. The inclusion criteria for the CP diagnosis were internally
      validated against patient records in 28% of the study population. SETTINGS: This
      was a nationwide population-based study. PATIENTS: A total of 307 patients (151
      men and 156 women) were identified and included (mean follow-up, 9 years; range,
      0-25 years). The inclusion criteria had a positive predictive value of 97% and a
      sensitivity of 92%. INTERVENTION: There were no interventions. MAIN OUTCOME
      MEASURES: Standardized mortality ratios (SMRs) and standardized incidence ratios
      (SIRs) with 95% confidence intervals were calculated using the Swedish population
      as the reference. RESULTS: During the study, 54 patients died compared with the
      expected number of 14.1, resulting in an SMR of 3.2 (2.2-4.7) for men and 4.9
      (3.2-7.2) for women. PATIENTS with childhood-onset (n = 106) and adult-onset (n =
      201) CP had SMRs of 17 (6.3-37) and 3.5 (2.6-4.6), respectively. PATIENTS with
      hypopituitarism (n = 250), diabetes insipidus (n = 110), and neither of these (n
      = 54) had SMRs of 4.3 (3.1-5.8), 6.1 (3.5-9.7), and 2.7 (1.4-4.6), respectively.
      The SMR due to cerebrovascular diseases was 5.1 (1.7-12). SIRs were 5.6 (3.8-8.0)
      for type 2 diabetes mellitus, 7.1 (5.0-9.9) for cerebral infarction, 0.7 (0.2
      1.7) for myocardial infarction, 2.1 (1.4-3.0) for fracture, and 5.9 (3.4-9.4) for
      severe infection. The SIR for all malignant tumors was 1.3 (0.8-2.1).
      CONCLUSIONS: This first nationwide population-based study of patients with CP
      demonstrated excess mortality that was especially marked in patients with
      childhood-onset disease and among women. Death due to cerebrovascular diseases
      was increased 5-fold. Hypopituitarism and diabetes insipidus were negative
      prognostic factors for mortality and morbidity. PATIENTS with CP had increased
      disease burden related to type 2 diabetes mellitus, cerebral infarction,
      fracture, and severe infection.

PMID- 25375986
TI  - Quantitation of CYP24A1 enzymatic activity with a simple two-hybrid system.
AB  - CONTEXT: Mutations of the CYP24A1 gene encoding the 24-hydroxylase (24OHase) that
      inactivates metabolites of vitamin D can cause hypercalcemia in infants and
      adults; in vitro assays of 24OHase activity have been difficult. OBJECTIVE: We
      sought an alternative assay to characterize a CYP24A1 mutation in a young adult
      with bilateral nephrolithiasis and hypercalcemia associated with ingestion of
      excess vitamin D supplements and robust dairy intake for 5 years. METHODS:
      CYP24A1 exons were sequenced from leukocyte DNA. Wild-type and mutant CYP24A1
      cDNAs were expressed in JEG-3 cells, and 24OHase activity was assayed by a two
      hybrid system. RESULTS: The CYP24A1 missense mutation L409S was found on only one
      allele; no other mutation was found in exons or in at least 30 bp of each
      intron/exon junction. Based on assays of endogenous 24OHase activity and of
      activity from a transiently transfected CYP24A1 cDNA expression vector, JEG-3
      cells were chosen over HepG2, Y1, MA10, and NCI-H295A cells for two-hybrid assays
      of 24OHase activity. The apparent Michaelis constant, Km(app), was 9.0 +/- 2.0 nM
      for CYP24A1 and 8.6 +/- 2.2 nM for its mutant; the apparent maximum velocity,
      Vmax(app), was 0.71 +/- 0.055 d(-1) for the wild type and 0.22 +/- 0.026 d(-1)
      for the mutant. As assessed by Vmax/Km, the L409S mutant has 32% of wild-type
      activity (P = .0012). CONCLUSIONS: The two-hybrid system in JEG-3 cells provides
      a simple, sensitive, quantitative assay of 24OHase activity. Heterozygous
      mutation of CYP24A1 may cause hypercalcemia in the setting of excessive vitamin D
      intake, but it is also possible that the patient had another, unidentified
      CYP24A1 mutation on the other allele.

PMID- 25375988
TI  - Origin of the phase transition in lithiated molybdenum disulfide.
AB  - Phase transitions and phase engineering in two-dimensional MoS2 are important for
      applications in electronics and energy storage. By in situ transmission electron
      microscopy, we find that H-MoS2 transforms to T-LiMoS2 at the early stages of
      lithiation followed by the formation of Mo and Li2S phases. The transition from H
      MoS2 to T-LiMoS2 is explained in terms of electron doping and electron-phonon
      coupling at the conduction band minima. Both are essential for the development of
      two-dimensional semiconductor-metal contacts based on MoS2 and the usage of MoS2
      as anode material in Li ion batteries. 

PMID- 25375989
TI  - Production and analysis of immunomodulatory excretory-secretory products from the
      mouse gastrointestinal nematode Heligmosomoides polygyrus bakeri.
AB  - Heligmosomoides polygyrus bakeri (Hpb) infection in mice is a convenient model
      for studying the pathophysiology and immunology of gastrointestinal (GI) helminth
      infection. Hpb infection suppresses immune responses to bystander antigens and
      unrelated pathogens, and it slows the progression and modifies the outcome of
      immune-mediated diseases. Hpb-derived excretory-secretory (ES) products potently
      modulate CD4(+) helper T cell (TH) responses by inducing regulatory T cells,
      tolerogenic dendritic cells (DCs) and immunoregulatory cytokines. This
      observation has spiked interest in identifying the immunomodulatory molecules,
      especially proteins, in ES products from Hpb and other GI nematodes for
      development as novel therapies to treat individuals with immune-mediated
      diseases, such as inflammatory bowel diseases (IBDs). In this protocol, we
      describe how to (i) maintain Hpb in the laboratory for experimental infections,
      (ii) collect adult worms from infected mice to generate ES products and (iii)
      evaluate the modulatory effects of ES products on toll-like receptor (TLR) ligand
      induced maturation of CD11c(+) DCs. The three major sections of the PROCEDURE can
      be used independently, and they require ~6, 10 and 27 h, respectively. Although
      other methods use a modified Baermann apparatus to collect Hpb adult worms, we
      describe a method that involves dissection of adult worms from intestinal tissue.
      The protocol will be useful to investigators studying the host-parasite interface
      and identifying and analyzing helminth-derived molecules with therapeutic
      potential. 

PMID- 25375990
TI  - A primary CD4(+) T cell model of HIV-1 latency established after activation
      through the T cell receptor and subsequent return to quiescence.
AB  - A mechanistic understanding of HIV-1 latency depends on a model system that
      recapitulates the in vivo condition of latently infected, resting CD4(+) T
      lymphocytes. Latency seems to be established after activated CD4(+) T cells, the
      principal targets of HIV-1 infection, become productively infected and survive
      long enough to return to a resting memory state in which viral expression is
      inhibited by changes in the cellular environment. This protocol describes an ex
      vivo primary cell system that is generated under conditions that reflect the in
      vivo establishment of latency. Creation of these latency model cells takes 12
      weeks and, once established, the cells can be maintained and used for several
      months. The resulting cell population contains both uninfected and latently
      infected cells. This primary cell model can be used to perform drug screens, to
      study cytolytic T lymphocyte (CTL) responses to HIV-1, to compare viral alleles
      or to expand the ex vivo life span of cells from HIV-1-infected individuals for
      extended study. 

PMID- 25375991
TI  - Antibody modeling using the prediction of immunoglobulin structure (PIGS) web
      server [corrected].
AB  - Antibodies (or immunoglobulins) are crucial for defending organisms from
      pathogens, but they are also key players in many medical, diagnostic and
      biotechnological applications. The ability to predict their structure and the
      specific residues involved in antigen recognition has several useful applications
      in all of these areas. Over the years, we have developed or collaborated in
      developing a strategy that enables researchers to predict the 3D structure of
      antibodies with a very satisfactory accuracy. The strategy is completely
      automated and extremely fast, requiring only a few minutes (~10 min on average)
      to build a structural model of an antibody. It is based on the concept of
      canonical structures of antibody loops and on our understanding of the way light
      and heavy chains pack together. 

PMID- 25375993
TI  - Pediatric nodular fasciitis in the head and neck: evaluation and management.
AB  - IMPORTANCE: Nodular fasciitis is a rare benign tumor that can present in the head
      and neck in children. A better understanding of this rare condition is critical
      to optimize management. OBJECTIVE: To review the presentation, evaluation,
      diagnosis, and management of pediatric nodular fasciitis of the head and neck.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of all patients treated
      for nodular fasciitis of the head and neck over a 20-year period at a pediatric
      tertiary care center. INTERVENTION: Surgical excision. MAIN OUTCOMES AND
      MEASURES: Clinical data, including age, presenting symptoms, anatomical site(s),
      evaluation, treatment, and complications. RESULTS: Fifteen children with
      pathologically confirmed nodular fasciitis of the head and neck were identified,
      including 8 boys and 7 girls. The median (range) age at diagnosis was 9.3 years
      (2 months to 18 years). Patients most commonly presented with a firm, enlarging
      soft-tissue mass. Two patients reported pain, and 1 patient presented with
      erythema. The most common location was the maxillofacial region (5 patients).
      Other locations included the scalp (3 patients), forehead (2 patients), neck (2
      patients), mandible (1 patient), postauricular region (1 patient), and nasal
      dorsum (1 patient). One patient reported a preceding trauma, and 1 patient, a
      preceding infection. Presurgical imaging varied; imaging modalities used included
      computed tomography, magnetic resonance imaging, radiography, ultrasound, and
      sialography. All patients underwent surgical excision, which focused on excising
      the mass while preserving surrounding normal tissues. Mean (range) follow-up was
      7.69 (0-46) months. Two minor complications were reported: 1 patient who
      underwent a near-total excisional biopsy experienced residual firmness and
      tenderness at the site of the lesion and another patient was left with an
      unfavorable cosmetic scar that necessitated intralesional steroid injection. No
      patient demonstrated recurrence at follow-up. CONCLUSIONS AND RELEVANCE: Although
      an uncommon diagnosis, nodular fasciitis should be considered in the evaluation
      and treatment of head and neck soft-tissue masses in children. Preoperative
      imaging is nonspecific and variable. Pathological findings are necessary for
      diagnosis. Surgical excisional biopsy is curative, with no instances of
      recurrence in our series.

PMID- 25375992
TI  - Anesthetized- and awake-patched whole-cell recordings in freely moving rats using
      UV-cured collar-based electrode stabilization.
AB  - Intracellular recording allows precise measurement and manipulation of individual
      neurons, but it requires stable mechanical contact between the electrode and the
      cell membrane, and thus it has remained challenging to perform in behaving
      animals. Whole-cell recordings in freely moving animals can be obtained by
      rigidly fixing ('anchoring') the pipette electrode to the head; however, previous
      anchoring procedures were slow and often caused substantial pipette movement,
      resulting in loss of the recording or of recording quality. We describe a UV
      transparent collar and UV-cured adhesive technique that rapidly (within 15 s)
      anchors pipettes in place with virtually no movement, thus substantially
      improving the reliability, yield and quality of freely moving whole-cell
      recordings. Recordings are first obtained from anesthetized or awake head-fixed
      rats. UV light cures the thin adhesive layers linking pipette to collar to head.
      Then, the animals are rapidly and smoothly released for recording during
      unrestrained behavior. The anesthetized-patched version can be completed in ~4-7
      h (excluding histology) and the awake-patched version requires ~1-4 h per day for
      ~2 weeks. These advances should greatly facilitate studies of neuronal
      integration and plasticity in identified cells during natural behaviors. 

PMID- 25375994
TI  - Evidence-based infant sleep recommendations.

PMID- 25375995
TI  - Nanocrystallized CdS beneath the surface of a photoconductor for detection of UV
      light with picowatt sensitivity.
AB  - In this study, we demonstrated that the improvement of detection capability of
      cadmium sulfide (CdS) photoconductors in the ultraviolet (UV) regime is much
      larger than that in the visible regime, suggesting that the deep UV laser-treated
      CdS devices are very suitable for low-light detection in the UV regime. We
      determined that a nanocrystallized CdS photoconductor can behave as a picowatt
      sensitive detector in the UV regime after ultra-shallow-region crystallization of
      the CdS film upon a single shot from a KrF laser. Photoluminescence and Raman
      spectra revealed that laser treatment increased the degree of crystallization of
      the CdS and led to the effective removal of defects in the region of a few tens
      nanometers beneath the surface of CdS, confirming the result by the transmission
      electron microscopy (TEM) images. Optical simulations suggested that UV light was
      almost completely absorbed in the shallow region beneath the surface of the CdS
      films, consistent with the observed region that underwent major crystal structure
      transformation. Accordingly, we noted a dramatic enhancement in responsivity of
      the CdS devices in the UV regime. Under a low bias voltage (1 mV), the treated
      CdS device provided a high responsivity of 74.7 A W(-1) and a detectivity of
      1.0*10(14) Jones under illumination with a power density of 1.9 nW cm(-2). Even
      when the power of the UV irradiation on the device was only 3.5 pW, the device
      exhibited extremely high responsivity (7.3*10(5) A W(-1)) and detectivity
      (3.5*10(16) Jones) under a bias voltage of 1 V. Therefore, the strategy proposed
      in this study appears to have great potential for application in the development
      of CdS photoconductors for picowatt-level detection of UV light with low power
      consumption.

PMID- 25375996
TI  - Xenogeneic acellular conjunctiva matrix as a scaffold of tissue-engineered
      corneal epithelium.
AB  - Amniotic membrane-based tissue-engineered corneal epithelium has been widely used
      in the reconstruction of the ocular surface. However, it often degrades too early
      to ensure the success of the transplanted corneal epithelium when treating
      patients with severe ocular surface disorders. In the present study, we
      investigated the preparation of xenogeneic acellular conjunctiva matrix (aCM) and
      evaluated its efficacy and safety as a scaffold of tissue-engineered corneal
      epithelium. Native porcine conjunctiva was decellularized with 0.1% sodium
      dodecyl sulfate (SDS) for 12 h at 37 degrees C and sterilized via gamma
      irradiation. Compared with native conjunctiva, more than 92% of the DNA was
      removed, and more than 90% of the extracellular matrix components
      (glycosaminoglycan and collagen) remained after the decellularization treatment.
      Compared with denuded amniotic membrane (dAM), the aCM possessed favorable
      optical transmittance, tensile strength, stability and biocompatibility as well
      as stronger resistance to degradation both in vitro and in vivo. The corneal
      epithelial cells seeded on aCM formed a multilayered epithelial structure and
      endured longer than did those on dAM. The aCM-based tissue-engineered corneal
      epithelium was more effective in the reconstruction of the ocular surface in
      rabbits with limbal stem cell deficiency. These findings support the application
      of xenogeneic acellular conjunctiva matrix as a scaffold for reconstructing the
      ocular surface. 

PMID- 25375997
TI  - Zinc complexes as fluorescent chemosensors for nucleic acids: new perspectives
      for a "boring" element.
AB  - Zinc(II) complexes are effective and selective nucleic acid-binders and strongly
      fluorescent molecules in the low energy range, from the visible to the near
      infrared. These two properties have often been exploited to quantitatively detect
      nucleic acids in biological samples, in both in vitro and in vivo models. In
      particular, the fluorescent emission of several zinc(II) complexes is drastically
      enhanced or quenched by the binding to nucleic acids and/or upon visible light
      exposure, in a different fashion in bulk solution and when bound to DNA. The
      twofold objective of this perspective is (1) to review recent utilisations of
      zinc(II) complexes as selective fluorescent probes for nucleic acids and (2) to
      highlight their novel potential applications as diagnostic tools based on their
      photophysical properties.

PMID- 25375998
TI  - Guidelines for conducting rigorous health care psychosocial cross
      cultural/language qualitative research.
AB  - The purpose of this article is to synthesize and chronicle the authors'
      experiences as four bilingual and bicultural researchers, each experienced in
      conducting cross-cultural/cross-language qualitative research. Through narrative
      descriptions of experiences with Latinos, Iranians, and Hmong refugees, the
      authors discuss their rewards, challenges, and methods of enhancing rigor,
      trustworthiness, and transparency when conducting cross-cultural/cross-language
      research. The authors discuss and explore how to effectively manage cross
      cultural qualitative data, how to effectively use interpreters and translators,
      how to identify best methods of transcribing data, and the role of creating
      strong community relationships. The authors provide guidelines for health care
      professionals to consider when engaging in cross-cultural qualitative research. 

PMID- 25376000
TI  - Ticagrelor for the treatment of peripheral arterial disease.
AB  - INTRODUCTION: Peripheral arterial disease (PAD) is a manifestation, and marker of
      severity, of a generalized atherosclerotic process. Antiplatelet therapy is
      recommended to prevent cardiovascular events but much of the evidence to support
      this is drawn from studies on older drugs. AREAS COVERED: In this review, the
      authors discuss the available evidence for the basis of current recommendations
      and review the data from Phase I to III trials on ticagrelor as a potential
      future treatment. This paper also reviews the properties of ticagrelor, its
      adverse effects, and how it differs from current recommended antiplatelet agents.
      As it is also more potent, a personalized approach to antiplatelet therapy may
      prove useful. It further highlights the additional effects of ticagrelor mediated
      by adenosine and their potential benefits, which may provide an explanation to
      its superior outcomes in trials comparing it with clopidogrel. EXPERT OPINION:
      Although there is a current lack of evidence to support the use of ticagrelor in
      patients with PAD, its unique pleomorphic properties make it attractive for
      future investigations and development of similar drugs.

PMID- 25375999
TI  - Effect of global cardiac ischemia on human ventricular fibrillation: insights
      from a multi-scale mechanistic model of the human heart.
AB  - Acute regional ischemia in the heart can lead to cardiac arrhythmias such as
      ventricular fibrillation (VF), which in turn compromise cardiac output and result
      in secondary global cardiac ischemia. The secondary ischemia may influence the
      underlying arrhythmia mechanism. A recent clinical study documents the effect of
      global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global
      ischemia the dominant frequency of activation decreased, while after reperfusion
      it increased rapidly. At the same time the complexity of epicardial excitation,
      measured as the number of epicardical phase singularity points, remained
      approximately constant during ischemia. Here we perform numerical studies based
      on these clinical data and propose explanations for the observed dynamics of the
      period and complexity of activation patterns. In particular, we study the effects
      on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an
      anatomically accurate model of human heart ventricles. We demonstrate that the
      fall of dominant frequency in VF during secondary ischemia can be explained by an
      increase in extracellular potassium, while the increase during reperfusion is
      consistent with washout of potassium and continued activation of the ATP
      dependent potassium channels. We also suggest that memory effects are responsible
      for the observed complexity dynamics. In addition, we present unpublished
      clinical results of individual patient recordings and propose a way of estimating
      extracellular potassium and activation of ATP-dependent potassium channels from
      these measurements. 

PMID- 25376001
TI  - Re-interventions following laparoscopic surgery for colorectal cancer: data from
      818 individuals from the Dutch surgical colorectal audit.
AB  - BACKGROUND: The surgical procedure of choice for the resection of colorectal
      cancer has shifted in favor of laparoscopic surgery. Although increasing data
      prove advantages of elective laparoscopic surgery, less is known about the
      results in acute indications such as surgical re-interventions following
      colorectal resections. This study aims to assess the clinical benefits in
      recovery following laparoscopic re-interventions compared with open re
      interventions following laparoscopic colorectal cancer surgery. SUBJECTS AND
      METHODS: We performed an analysis of data from the Dutch Surgical Colorectal
      Audit from January 2010 to December 2012. All patients requiring surgical re
      intervention after initial laparoscopic colorectal surgery were analyzed.
      RESULTS: Out of 27,448 patients, 11,856 underwent laparoscopic surgery. Following
      laparoscopic surgery, 159 patients (1.3%) had a laparoscopic re-intervention, and
      659 patients (5.6%) had an open re-intervention. In a multivariable analysis
      adjusting for patients' demographics and risk factors, the length of hospital
      stay was 17 days (interquartile range, 11-16 days) for the laparoscopic group and
      23 days (interquartile range, 14-37 days) for the open group (odds ratio
      [OR]=0.74; 95% confidence interval [CI], 0.65-0.84). In the laparoscopic group
      the intensive care unit admission rate was 39% compared with 66% in the open
      group. The 30-day mortality rate was 7 (4%) in the laparoscopic group compared
      with 89 (14%) in the open group (OR=0.31; 95% CI, 0.13-0.73). CONCLUSIONS:
      Laparoscopic re-intervention following laparoscopic surgery for colorectal cancer
      is feasible in selected patients. Because of the unknown extent of selection
      bias, prospective studies are needed to define the exact position and benefits of
      laparoscopic re-interventions.

PMID- 25376002
TI  - Challenge or opportunity: outcomes of laparoscopic resection for rectal cancer in
      patients with high operative risk.
AB  - This study investigated the impact of laparoscopic rectal cancer resection for
      patients with high operative risk, which was defined as American Society of
      Anesthesiology (ASA) grades III and IV. This study was conducted at a single
      center on patients undergoing rectal resection from 2006 to 2010. After screening
      by ASA grade III or IV, 248 patients who met the inclusion criteria were
      identified, involving 104 open and 144 laparoscopic rectal resections. The
      distribution of the Charlson Comorbidity Index was similar between the two
      groups. Compared with open rectal resection, laparoscopic resection had a
      significantly lower total complication rate (P<.0001), lower pain rate (P=.0002),
      and lower blood loss (P<.0001). It is notable that the two groups of patients had
      no significant difference in cardiac and pulmonary complication rates. Thus,
      these data showed that the laparoscopic group for rectal cancer could provide
      short-term outcomes similar to those of their open resection counterparts with
      high operative risk. The 5-year actuarial survival rates were 0.8361 and 0.8119
      in the laparoscopic and open groups for stage I/II (difference not significant),
      as was the 5-year overall survival rate in stage III/IV (P=.0548). In patients
      with preoperative cardiovascular or pulmonary disease, the 5-year survival curves
      were significantly different (P=.0165 and P=.0210), respectively. The cost per
      patient did not differ between the two procedures. The results of this analysis
      demonstrate the potential advantages of laparoscopic rectal cancer resection for
      high-risk patients, although a randomized controlled trial should be conducted to
      confirm the findings of the present study.

PMID- 25376003
TI  - Strategies to decrease bile duct injuries during laparoscopic cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) has been performed clinically for
      more than 20 years. However, the incidence of bile duct injury (BDI) remains high
      despite attempts to prevent and reduce it. The aim of this study was to use an
      intraoperative unfavorable factors ratings system to identify unfavorable
      intraoperative factors and evaluate the effectiveness of application of the
      system in reducing BDI during LC. PATIENTS AND METHODS: Between January 2009 and
      December 2010, 780 patients who underwent LC were reviewed retrospectively,
      including 384 LC patients without graded treatment of intraoperative unfavorable
      factors (GTIUF) during 2009 and 396 LC patients with routine GTIUF during 2010.
      RESULTS: BDI was decreased significantly after routine GTIUF (5 cases without
      GTIUF versus 0 cases with routine GTIUF; P=.029). There was no significant
      difference in postoperative morbidity and mortality between the two groups. The
      mean operation duration of the routine GTIUF group was prolonged significantly
      (P<.0001). Laparoscopic cholecystitis grading, GTIUF, and doctor's experience
      were important factors affecting the duration of operation (P<.0001, P<.0001, and
      P<.0001, respectively). CONCLUSIONS: GTIUF is an effective method that emphasizes
      identification of the course of the extrahepatic bile duct and reduces the
      occurrence of BDI, especially for inexperienced operators.

PMID- 25376004
TI  - 3-year follow-up after uniportal thoracoscopic sympathicotomy for hyperhidrosis:
      undesirable side effects.
AB  - OBJECTIVE: Endoscopic thoracic sympathectomy or sympathicotomy, for the treatment
      of palmar, axillary, and plantar hyperhidrosis, is generally performed at one or
      two levels, between T2 and T5. Compensatory sweating (CS) is a severe and
      undesirable side effect of this procedure. Here, we describe the success of
      treatment and degree of postoperative CS in sympathicotomy patients. SUBJECTS AND
      METHODS: This study included 80 patients treated by uniportal (5-mm)
      thoracoscopic sympathicotomy (electrocautery) for primary hyperhidrosis over a 6
      year period (2007-2013). Sympathicotomy was performed bilaterally at T2 for
      blushing (n=2), T2-T3 for palmar-only hyperhidrosis (n=34), T2-T4 for palmar and
      axillary hyperhidrosis (n=39), and T3-T4 for axillary-only hyperhidrosis (n=5).
      Outcome was assessed 2 weeks postsurgery at the clinic and annually thereafter by
      telephone questionnaire. Mean follow-up time was 35.2+/-23.3 months.
      Questionnaires assessed patients' degree of sweating, postoperative CS, overall
      satisfaction, and complications. RESULTS: Seventy-one patients (88.7%) were very
      satisfied, whereas only 9 (11.3%) were dissatisfied with the procedure.
      Complication incidence was 7.5%, and CS occurred in 77.5% of patients.
      Therapeutic success rate was 97.5%; complete relief of hyperhidrosis was achieved
      in 72 (90%) patients, whereas 8 (10%) experienced recurrence. CONCLUSIONS: CS is
      a frequent side effect of thoracoscopic sympathicotomy. We recommend all patients
      undergoing this procedure should be warned of the potential risk of developing
      severe CS.

PMID- 25376005
TI  - Single-incision laparoscopic splenectomy with conventional instruments:
      preliminary experience in consecutive patients and comparison to standard
      multiple-incision laparoscopic splenectomy.
AB  - AIM: To study the feasibility and efficiency of transumbilical single-incision
      laparoscopic surgery splenectomy (SILS-Sp) using conventional instruments in
      consecutive patients and to compare outcomes of the procedure with those of
      standard multiple-incision laparoscopic splenectomy (MLS). PATIENTS AND METHODS:
      A retrospective review was conducted to evaluate all SILS-Sp procedures performed
      by a single surgeon between March 2010 and January 2013. Additionally, patients
      who underwent MLS by other surgeons in the same surgical group during the same
      period were evaluated to serve as a control group. Demographic data, operative
      parameters, and postoperative outcomes were assessed. RESULTS: Thirteen patients
      underwent successful SILS-Sp during the study period without conversion to an
      open procedure or requiring additional ports. The median operative time was 165
      minutes. There was 7.7% morbidity and no mortality in the study group. Median
      length of stay was 8.8 days. Additionally, 12 patients who underwent MLS were
      evaluated for comparison. No significant differences were identified in the
      preoperative patient characteristics between the two groups. For MLS, the median
      operative time was 158 minutes. There was 8.3% morbidity and no mortality in the
      group. Median length of stay was 8.3 days. SILS-Sp using conventional instruments
      was associated with reduced postoperative pain scores, but this did not reach
      statistical significance. The operative time, conversion rate, and length of stay
      were equivalent. The mortality, morbidity, and cost were also similar in the two
      groups. The umbilical incision of the single-incision group can be easily hidden
      in the umbilical fold with ideal cosmetic result. CONCLUSIONS: SILS-Sp is
      feasible and efficient in an unselected patient population in the hands of an
      experienced laparoscopic surgeon. The single-incision technique is comparable to
      standard laparoscopic splenectomy in terms of operative time and perioperative
      outcomes. Ideal cosmetic effect may be its potential advantage.

PMID- 25376006
TI  - Radical robotic-assisted laparoscopic prostatectomy: a daycase procedure.

PMID- 25376007
TI  - The cultural validation of two scales to assess social stigma in leprosy.
AB  - BACKGROUND: Stigma plays in an important role in the lives of persons affected by
      neglected tropical diseases, and assessment of stigma is important to document
      this. The aim of this study is to test the cross-cultural validity of the
      Community Stigma Scale (EMIC-CSS) and the Social Distance Scale (SDS) in the
      field of leprosy in Cirebon District, Indonesia. METHODOLOGY/PRINCIPLE FINDINGS:
      Cultural equivalence was tested by assessing the conceptual, item, semantic,
      operational and measurement equivalence of these instruments. A qualitative
      exploratory study was conducted to increase our understanding of the concept of
      stigma in Cirebon District. A process of translation, discussions, trainings and
      a pilot study followed. A sample of 259 community members was selected through
      convenience sampling and 67 repeated measures were obtained to assess the
      psychometric measurement properties. The aspects and items in the SDS and EMIC
      CSS seem equally relevant and important in the target culture. The response
      scales were adapted to ensure that meaning is transferred accurately and no
      changes to the scale format (e.g. lay out, statements or questions) of both
      scales were made. A positive correlation was found between the EMIC-CSS and the
      SDS total scores (r=0.41). Cronbach's alphas of 0.83 and 0.87 were found for the
      EMIC-CSS and SDS. The exploratory factor analysis indicated for both scales an
      adequate fit as unidimensional scale. A standard error of measurement of 2.38 was
      found in the EMIC-CSS and of 1.78 in the SDS. The test-retest reliability
      coefficient was respectively, 0.84 and 0.75. No floor or ceiling effects were
      found. CONCLUSIONS/SIGNIFICANCE: According to current international standards,
      our findings indicate that the EMIC-CSS and the SDS have adequate cultural
      validity to assess social stigma in leprosy in the Bahasa Indonesia-speaking
      population of Cirebon District. We believe the scales can be further improved,
      for instance, by adding, changing and rephrasing certain items. Finally, we
      provide suggestions for use with other neglected tropical diseases.

PMID- 25376008
TI  - Signs of right ventricular deterioration in clinically stable patients with
      pulmonary arterial hypertension.
AB  - BACKGROUND: Even after years of stable response to therapy, patients with
      idiopathic pulmonary arterial hypertension (IPAH) may show an unexpected clinical
      deterioration due to progressive right ventricular (RV) failure. Therefore, the
      aim of this study was to assess in 5-year clinically stable patients with IPAH
      whether initial differences or subsequent changes in RV volumes precede late
      clinical progression. METHODS: Included were 22 clinically stable patients with
      IPAH as reflected by stable or improving New York Heart Association functional
      class II-III and exercise capacity during 5 years of follow-up. Twelve patients
      subsequently remained stable during a total follow-up of 10 years, whereas 10
      other patients showed late progression leading to death or lung transplantation
      after a follow-up of 8 years. All patients underwent right-sided heart
      catheterization and cardiac MRI at baseline and at 11/2, 31/2, 61/2, and, if
      still alive, 10 years follow-up. RESULTS: Baseline hemodynamics were comparable
      in both groups and remained unchanged during the entire follow-up period.
      Baseline RV end-systolic volume (RVESV) was higher and RV ejection fraction
      (RVEF) was lower in late-progressive patients. Late-progressive patients
      demonstrated a gradually increased RV end-diastolic volume and RVESV and a
      decline in RVEF, whereas long-term stable patients did not show any RV changes.
      CONCLUSIONS: In patients with stable IPAH for 5 years, subsequent late disease
      progression is preceded by changes in RV volumes. The results indicate that
      monitoring RV volumes anticipates clinical worsening, even at a time of apparent
      clinical stability.

PMID- 25376009
TI  - Thiol-promoted selective addition of ketones to aldehydes.
AB  - A simple and efficient thiol-mediated addition of ketones to aromatic and
      aliphatic aldehydes is reported. This thermodynamically controlled Pummerer/aldol
      reaction, which can tolerate both moisture and protic functional groups, provides
      a direct entry to syn-beta-thioketones in high chemo- and regioselectivity.
      Mechanistic studies revealed that selective transformation of the aldehyde to an
      electrophilic thionium ion species concurrent with the generation of a
      nucleophilic vinyl sulfide coupling partner from the ketone is imposing cross
      coupling over dimerization. 

PMID- 25376010
TI  - Voluntary modulation of anterior cingulate response to negative feedback.
AB  - Anterior cingulate and medial frontal cortex (dACC/mFC) response to negative
      feedback represents the actions of a generalized error-monitoring system critical
      for the management of goal-directed behavior. Magnitude of dACC/mFC response to
      negative feedback correlates with levels of post-feedback behavioral change, and
      with proficiency of operant learning processes. With this in mind, it follows
      that an ability to alter dACC/mFC response to negative feedback may lead to
      representative changes in operant learning proficiency. To this end, the present
      study investigated the extent to which healthy individuals would show modulation
      of their dACC/mFC response when instructed to try to either maximize or minimize
      their neural response to the presentation of contingent negative feedback.
      Participants performed multiple runs of a standard time-estimation task, during
      which they received feedback regarding their ability to accurately estimate a one
      second duration. On Watch runs, participants were simply instructed to try to
      estimate as closely as possible the one second duration. On Increase and Decrease
      runs, participants performed the same task, but were instructed to "try to
      increase [decrease] their brain's response every time they received negative
      feedback". Results indicated that participants showed changes in dACC/mFC
      response under these differing instructional conditions: dACC/mFC activity
      following negative feedback was higher in the Increase condition, and dACC
      activity trended lower in the Decrease condition, compared to the Watch
      condition. Moreover, dACC activity correlated with post-feedback performance
      adjustments, and these adjustments were highest in the Increase condition.
      Potential implications for neuromodulation and facilitated learning are
      discussed. 

PMID- 25376011
TI  - A longitudinal magnetization transfer imaging evaluation of brain injury in a
      macaque model of neuroAIDS.
AB  - Magnetization transfer (MT) imaging has been explored in prior studies of HIV
      patients and showed the potential capacity to assess brain injury after HIV
      infection. In the present study, adult pig-tailed macaques were infected with a
      highly neuropathogenic virus SIVsmmFGb. MT imaging was exploited to examine the
      monkey brains before simian immunodeficiency virus (SIV) inoculation and 2, 4, 8,
      12, 16, and 20 weeks post-SIV inoculation. Blood samples were collected from each
      animal for monitoring CD4(+) and CD8(+) T cells before each MRI scan. The MT
      ratios (MTR) in several brain regions of interest were evaluated longitudinally.
      Significant reductions of MTR were observed in whole brain and selected regions
      of interest (genu, splenium, thalamus, caudate, centrum semiovale, frontal white
      matter, frontal gray matter, and putamen) in the SIV-infected monkeys, consistent
      with those reported previously in HIV patients. In particular, the longitudinal
      results indicate that abnormal MTR reduction can be detected as early as in 2
      weeks and MTR may be more sensitive to the brain injury in cortical regions than
      in subcortical regions during acute SIV infection. In addition, MTR reduction in
      genu, centrum semiovale, and thalamus significantly correlated with the CD4(+) T
      cell percentage decrease. Also, the MTR reduction in thalamus correlated with the
      CD8(+) T cell percentage elevation. Taken together, this study reported the
      longitudinal evolution of MTR in different brain regions during SIV infection and
      further validates previous findings in HIV patients. The preliminary results
      suggest that MT imaging could be a robust and sensitive approach to characterize
      the neurodegeneration after SIV or HIV infection. 

PMID- 25376013
TI  - Chemotaxonomy of Hawaiian Anthurium cultivars based on multivariate analysis of
      phenolic metabolites.
AB  - Thirty-six anthurium varieties, sampled from species and commercial cultivars,
      were extracted and profiled by liquid-chromatography-mass spectrometry (HPLC-MS).
      Three hundred fifteen compounds, including anthocyanins, flavonoid glycosides,
      and other phenolics, were detected from these extracts and used in chemotaxonomic
      analysis of the specimens. Hierarchical cluster analysis (HCA) revealed close
      chemical similarities between all the commercial standard cultivars, while tulip
      shaped cultivars and species displayed much greater chemical variation. Principal
      component analysis (PCA) and partial least squares discriminant analysis (PLS-DA)
      supported the results from HCA and were used to identify key metabolites
      characteristic of standard and tulip cultivars and to identify chemical markers
      indicative of a particular ancestry. Discriminating metabolites included embinin,
      4, which was characteristic of standard-shaped spathes and indicated ancestry
      from Anthurium andraeanum, while isocytisoside 7-glucoside, 7, was found in the
      majority of tulip-shaped cultivars and suggested that Anthurium amnicola or
      Anthurium antioquiense had contributed to their pedigree. 

PMID- 25376012
TI  - Fatal cutaneous mucormycosis after kidney transplant.
AB  - Mucormycosis is an uncommon opportunistic infection that is caused by Mucorales
      from the Zygomycetes class. Patients with severe immunodeficiency admitted to the
      hospital are at greatest risk for developing this infection. Mucormycosis usually
      is transmitted in humans by inhalation or inoculation of spores in the skin or
      mucous membranes. A 66-year-old man developed a surgical wound infection at 1
      week after kidney transplant that did not improve despite broad-spectrum
      antibiotics and debridement. He was transferred to our hospital 45 days after
      transplant and had fever and a large purulent wound that was surrounded by a
      black necrotizing margin. Immunosuppressive drugs were discontinued and the
      dosage of prednisolone was decreased. Massive debridement was performed but was
      incomplete because he had full-thickness abdominal wall necrosis. Histopathology
      showed broad fungal hyphae without septation, consistent with the diagnosis of
      mucormycosis. Despite antifungal therapy with amphotericin B and additional
      debridement, the patient died of septic shock at 52 days after kidney transplant.
      Cutaneous fungal infections should be considered in the differential diagnosis of
      any nonhealing infected wound that does not respond to broad-spectrum
      antibiotics, especially in patients with predisposing risk factors such as
      transplant. 

PMID- 25376014
TI  - Multichromophoric bimetallic Ru(II) terpyridine complexes based on pyrenyl-bis
      phenylimidazole spacer: synthesis, photophysics, spectroelectrochemistry, and TD
      DFT calculations.
AB  - A symmetrical bridging ligand, 5,11-bis(4-([2,2':6',2"-terpyridine]-4'-yl)phenyl)
      4,12-dihydropyreno[4,5-d:9,10-d']diimidazole (tpy-H2PhImzPy-tpy), containing
      terpyridyl coordinating units connected via a pyrenyl-bis-phenylimidazole spacer
      have been designed to synthesize a new class of light harvesting bimetallic
      Ru(II) complexes. The electronic properties of this complexes can be fine-tuned
      by varying tridentate terminal ligands. Full characterization of the compounds
      has been done with the help of (1)H NMR spectroscopy, high-resolution mass
      spectrometry, and elemental analysis. Geometry optimization of the complexes was
      also carried out with density functional theory (DFT). Electronic absorption
      spectra exhibit a number of very intense pi-pi* and n-pi* transitions in the UV
      and moderately intense MLCT and ILCT transitions in the visible region.
      Interestingly, the present bimetallic complexes exhibit moderately strong
      luminescence in the range between 657 and 703 nm and lifetimes (long component)
      between 5.8 and 67.0 ns at room temperature showing the dependence of the
      emission characteristics upon the type of terminal ligand and solvent. Detailed
      temperature-dependent emission measurements showed that an overall enhancement of
      photoluminescence intensity and lifetime occur in all three cases upon lowering
      of temperature. The redox behavior of the compounds is characterized by a single
      reversible anodic wave corresponding to two closely spaced one-electron
      processes. The appearance of intervalence charge transfer transition (IVCT) bands
      in the NIR region on electrochemical generation of Ru(II)Ru(II)/Ru(II)Ru(III)
      species indicates the presence of substantial electronic communication among the
      two ruthenium centers in the bimetallic complexes. DFT and TDDFT calculations
      were also done for better understanding of the absorption and emission spectral
      characteristics of the complexes. 

PMID- 25376015
TI  - The impact of cooking classes on food-related preferences, attitudes, and
      behaviors of school-aged children: a systematic review of the evidence, 2003
      2014.
AB  - INTRODUCTION: Cooking programs have been used to promote healthful eating among
      people of all ages. This review assesses the evidence on childhood cooking
      programs and their association with changes in food-related preferences,
      attitudes, and behaviors of school-aged children. METHODS: We systematically
      searched PubMed, Ovid-Medline, and CINAHL (Cumulative Index to Nursing and Allied
      Health Literature) databases. We included primary research articles that involved
      cooking education programs for children and searched reference lists for eligible
      articles. Studies considered for review contained a hands-on cooking
      intervention; had participants aged 5 to 12 years; were published in a peer
      reviewed journal on or after January 1, 2003; and were written in English. We
      used the Effective Public Health Practice Project Quality Assessment Tool for
      Quantitative Studies to rate the strength of each article and assess bias. The
      following information was extracted from each study: study design, sample size,
      location, duration, intervention components, data collection methods, and
      outcomes. RESULTS: Eight studies met the inclusion criteria and used cooking
      education to influence children's food-related preferences, attitudes, and
      behaviors. Programs varied in duration, evaluation methods, and outcomes of
      interest. Self-reported food preparation skills, dietary intake, cooking
      confidence, fruit and vegetable preferences, attitudes toward food and cooking,
      and food-related knowledge were among the outcomes measured. Program exposure
      ranged from 2 sessions to regular instruction over 2 years, and the effect of
      cooking programs on children's food-related preferences, attitudes, and behaviors
      varied among the reviewed studies. CONCLUSIONS: Findings suggest that cooking
      programs may positively influence children's food-related preferences, attitudes,
      and behaviors. However, because study measurements varied widely, determining
      best practices was difficult. Further research is needed to fill knowledge gaps
      on ideal program length, long-term effects, and usefulness of parent engagement,
      tasting lessons, and other intervention components.

PMID- 25376016
TI  - Using the community readiness model to examine the built and social environment:
      a case study of the High Point neighborhood, Seattle, Washington, 2000-2010.
AB  - BACKGROUND: Residents of many cities lack affordable, quality housing.
      Economically disadvantaged neighborhoods often have high rates of poverty and
      crime, few institutions that enhance the quality of its residents' lives, and
      unsafe environments for walking and other physical activity. Deteriorating
      housing contributes to asthma-related illness. We describe the redevelopment of
      High Point, a West Seattle neighborhood, to improve its built environment,
      increase neighborhood physical activity, and reduce indoor asthma triggers.
      COMMUNITY CONTEXT: High Point is one of Seattle's most demographically diverse
      neighborhoods. Prior to redevelopment, it had a distressed infrastructure, rising
      crime rates, and indoor environments that increased asthma-related illness in
      children and adolescents. High Point residents and partners developed and
      implemented a comprehensive redevelopment plan to create a sustainable built
      environment to increase outdoor physical activity and improve indoor
      environments. METHODS: We conducted a retrospective analysis of the High Point
      redevelopment, organized by the different stages of change in the Community
      Readiness Model. We also examined the multisector partnerships among government
      and community groups that contributed to the success of the High Point project.
      OUTCOME: Overall quality of life for residents improved as a result of
      neighborhood redevelopment. Physical activity increased, residents reported fewer
      days of poor physical or mental health, and social connectedness between
      neighbors grew. Asthma-friendly homes significantly decreased asthma-related
      illness among children and adolescents. INTERPRETATION: Providing affordable,
      quality housing to low-income families improved individual and neighborhood
      quality of life. Efforts to create social change and improve the health outcomes
      for entire populations are more effective when multiple organizations work
      together to improve neighborhood health.

PMID- 25376017
TI  - Using simulation to compare established and emerging interventions to reduce
      cardiovascular disease risk in the United States.
AB  - INTRODUCTION: Computer simulation offers the ability to compare diverse
      interventions for reducing cardiovascular disease risks in a controlled and
      systematic way that cannot be done in the real world. METHODS: We used the
      Prevention Impacts Simulation Model (PRISM) to analyze the effect of 50
      intervention levers, grouped into 6 (2 x 3) clusters on the basis of whether they
      were established or emerging and whether they acted in the policy domains of care
      (clinical, mental health, and behavioral services), air (smoking, secondhand
      smoke, and air pollution), or lifestyle (nutrition and physical activity).
      Uncertainty ranges were established through probabilistic sensitivity analysis.
      RESULTS: Results indicate that by 2040, all 6 intervention clusters combined
      could result in cumulative reductions of 49% to 54% in the cardiovascular risk
      related death rate and of 13% to 21% in risk factor-attributable costs. A
      majority of the death reduction would come from Established interventions, but
      Emerging interventions would also contribute strongly. A slim majority of the
      cost reduction would come from Emerging interventions. CONCLUSION: PRISM allows
      public health officials to examine the potential influence of different types of
      interventions - both established and emerging - for reducing cardiovascular
      risks. Our modeling suggests that established interventions could still
      contribute much to reducing deaths and costs, especially through greater use of
      well-known approaches to preventive and acute clinical care, whereas emerging
      interventions have the potential to contribute significantly, especially through
      certain types of preventive care and improved nutrition.

PMID- 25376018
TI  - Dentists' self-perceived role in offering tobacco cessation services: results
      from a nationally representative survey, United States, 2010-2011.
AB  - INTRODUCTION: Dental visits represent an opportunity to identify and help
      patients quit smoking, yet dental settings remain an untapped venue for treatment
      of tobacco dependence. The purpose of this analysis was to assess factors that
      may influence patterns of tobacco-use-related practice among a national sample of
      dental providers. METHODS: We surveyed a representative sample of general
      dentists practicing in the United States (N = 1,802). Multivariable analysis was
      used to assess correlates of adherence to tobacco use treatment guidelines and to
      analyze factors that influence providers' willingness to offer tobacco cessation
      assistance if reimbursed for this service. RESULTS: More than 90% of dental
      providers reported that they routinely ask patients about tobacco use, 76%
      counsel patients, and 45% routinely offer cessation assistance, defined as
      referring patients for cessation counseling, providing a cessation prescription,
      or both. Results from multivariable analysis indicated that cessation assistance
      was associated with having a practice with 1 or more hygienists, having a chart
      system that includes a tobacco use question, having received training on treating
      tobacco dependence, and having positive attitudes toward treating tobacco use.
      Providers who did not offer assistance but who reported that they would change
      their practice patterns if sufficiently reimbursed were more likely to be in a
      group practice, treat patients insured through Medicaid, and have positive
      attitudes toward treating tobacco dependence. CONCLUSION: Findings indicate the
      potential benefit of increasing training opportunities and promoting system
      changes to increase involvement of dental providers in conducting tobacco use
      treatment. Reimbursement models should be tested to assess the effect on dental
      provider practice patterns.

PMID- 25376022
TI  - Novel synthesis of the ABC rings of solanoeclepin A.
AB  - A stereocontrolled synthesis of the ABC rings of solanoeclepin A has been
      achieved. The seven-membered ring B was synthesized by an intramolecular Prins
      ene reaction between an aldehyde and an enyne-dicobalthexacarbonyl complex. The
      acetylene in this synthesis plays multiple roles: to join the A and C rings, to
      allow stereoselective cyclization via dicobalthexacarbonyl complexation, and to
      facilitate Nicholas cation stabilization followed by deprotonation to form an
      endo-cyclic olefin (Nicholas-Prins cyclization). 

PMID- 25376023
TI  - Drugs in early clinical development for the treatment of female sexual
      dysfunction.
AB  - INTRODUCTION: There is growing recognition of female sexual dysfunction (FSD) as
      an important women's health concern. Despite an increased awareness of the
      pathophysiologic components to FSD, currently, there are no drugs approved for
      the most common sexual complaint in women-decreased sexual desire. In response to
      an overwhelming demand for therapy for FSD, several drugs are undergoing
      development and testing. AREAS COVERED: The aim of this paper is to provide the
      latest data on pharmacological treatments for FSD currently in Phase I and II
      clinical trials. These include topical alprostadil, bremelanotide (BMT),
      intranasal testosterone (TBS-2), intravaginal dehydroepiandrosterone (DHEA),
      sublingual testosterone with sildenafil, apomorphine (APO), bupropprion and
      trazodone. It should be noted that the definitions of FSD have recently been
      revised in the diagnostic and statistical manual for mental disorders (DSM) 5,
      with merging of hypoactive sexual desire disorder (HSDD) and female sexual
      arousal disorder (FSAD) into female sexual interest/arousal disorder (FSIAD).
      However, it is noted that the majority of clinical trials discussed in this paper
      use the DSM IV-R diagnoses of HSDD and FSAD. EXPERT OPINION: Medications in early
      phase trials show promise for the treatment of FSD. These therapies focus on
      treating many possible causes of FSD. Concerns over gender bias within the FDA
      need to be resolved given the need for new treatment options for FSD.

PMID- 25376021
TI  - Relationships between Th1 or Th2 iNKT cell activity and structures of CD1d
      antigen complexes: meta-analysis of CD1d-glycolipids dynamics simulations.
AB  - A number of potentially bioactive molecules can be found in nature. In
      particular, marine organisms are a valuable source of bioactive compounds. The
      activity of an alpha-galactosylceramide was first discovered in 1993 via
      screening of a Japanese marine sponge (Agelas mauritanius). Very rapidly, a
      synthetic glycololipid analogue of this natural molecule was discovered, called
      KRN7000. Associated with the CD1d protein, this alpha-galactosylceramide 1
      (KRN7000) interacts with the T-cell antigen receptor to form a ternary complex
      that yields T helper (Th) 1 and Th2 responses with opposing effects. In our work,
      we carried out molecular dynamics simulations (11.5 us in total) involving eight
      different ligands (conducted in triplicate) in an effort to find out correlation
      at the molecular level, if any, between chemical modulation of 1 and the
      orientation of the known biological response, Th1 or Th2. Comparative
      investigations of human versus mouse and Th1 versus Th2 data have been carried
      out. A large set of analysis tools was employed including free energy landscapes.
      One major result is the identification of a specific conformational state of the
      sugar polar head, which could be correlated, in the present study, to the
      biological Th2 biased response. These theoretical tools provide a structural
      basis for predicting the very different dynamical behaviors of alpha
      glycosphingolipids in CD1d and might aid in the future design of new analogues of
      1. 

PMID- 25376025
TI  - Understanding the adverse effects of ocriplasmin.

PMID- 25376026
TI  - Peritoneal Patch for an Occluded Venous Conduit of a Right Lobe During a Living
      Donor Liver Transplant.
AB  - Drainage of segments V and VIII venous tributaries usually is mandatory to avoid
      congestion of the anterior segment of right lobe during a living-donor liver
      transplant. Extension of the venous tributaries to the vena cava can be done with
      several vascular materials. Here, we describe using an 8 * 3 cm vascular patch
      from the peritoneum over the venous conduit (which had become kinked) that
      drained segments V and VIII veins. Peritoneal reconstruction worked well during
      the early postoperative period and avoided congestion of the right anterior liver
      segment. During the late postoperative period, the conduit became occluded as do
      other grafts used to extend tributaries; however, the collaterals that developed
      prevented congestion of the anterior liver segment. Using part of the peritoneum
      as a venous graft during living-donor liver transplant can be a good alternative
      to the other vascular grafting options. Peritoneal grafting provides temporary
      drainage of the liver lobe, prevents congestion of the anterior section, and
      saves time creating venous collaterals. 

PMID- 25376024
TI  - Attenuated Listeria monocytogenes vectors overcome suppressive plasma factors
      during HIV infection to stimulate myeloid dendritic cells to promote adaptive
      immunity and reactivation of latent virus.
AB  - HIV-1 infection is characterized by myeloid dendritic cell (DC) dysfunction,
      which blunts the responsiveness to vaccine adjuvants. We previously showed that
      nonviral factors in HIV-seropositive plasma are partially responsible for
      mediating this immune suppression. In this study we investigated recombinant
      Listeria monocytogenes (Lm) vectors, which naturally infect and potently activate
      DCs from seronegative donors, as a means to overcome DC dysfunction associated
      with HIV infection. Monocyte-derived DCs were cocultured with plasma from HIV
      infected donors (HIV-moDCs) to induce a dysregulated state and infected with an
      attenuated, nonreplicative vaccine strain of Lm expressing full length clade B
      consensus gag (KBMA Lm-gag). Lm infection stimulated cytokine secretion
      [interleukin (IL)-12p70, tumor necrosis factor (TNF)-alpha, and IL-6] and Th-1
      skewing of allogeneic naive CD4 T cells by HIV-moDCs, in contrast to the
      suppressive effects observed by HIV plasma on moDCs on toll-like receptor ligand
      stimulation. Upon coculture of "killed" but metabolically active (KBMA) Lm-gag
      infected moDCs from HIV-infected donors with autologous cells, expansion of
      polyfunctional, gag-specific CD8(+) T cells was observed. Reactivation of latent
      proviruses by moDCs following Lm infection was also observed in models of HIV
      latency in a TNF-alpha-dependent manner. These findings reveal the unique ability
      of Lm vectors to contend with dysregulation of HIV-moDCs, while simultaneously
      possessing the capacity to activate latent virus. Concurrent stimulation of
      innate and adaptive immunity and disruption of latency may be an approach to
      reduce the pool of latently infected cells during HIV infection. Further study of
      Lm vectors as part of therapeutic vaccination and eradication strategies may
      advance this evolving field.

PMID- 25376027
TI  - Challenges and resilience in the lives of adults with sickle cell disease.
AB  - This qualitative study focused on the experiences of adults living with sickle
      cell disease (SCD) in the New York City area. Twenty-three individuals
      participated in one of three focus groups. The purpose of this study was to learn
      if appropriate health care for individuals with sickle cell disease, based on
      years of research, has been implemented. The findings indicate that best
      practices in the treatment of SCD are often not followed by medical personnel.
      Critical race theory provides a framework to understand the 10 emergent themes.
      The participants' responses illustrate resilience in facing adversity.
      Implications for social work practice are presented. 

PMID- 25376029
TI  - Presumed bee stinger retained intraocularly in the absence of inflammation.

PMID- 25376030
TI  - Exponential integrators for a Markov chain model of the fast sodium channel of
      cardiomyocytes.
AB  - The modern Markov chain models of ionic channels in excitable membranes are
      numerically stiff. The popular numerical methods for these models require very
      small time steps to ensure stability. Our objective is to formulate and test two
      methods addressing this issue, so that the timestep can be chosen based on
      accuracy rather than stability. Both proposed methods extend Rush-Larsen
      technique, which was originally developed to Hogdkin-Huxley type gate models. One
      method, "matrix Rush-Larsen" (MRL) uses a matrix reformulation of the Rush-Larsen
      scheme, where the matrix exponentials are calculated using precomputed tables of
      eigenvalues and eigenvectors. The other, "hybrid operator splitting" (HOS) method
      exploits asymptotic properties of a particular Markov chain model, allowing
      explicit analytical expressions for the substeps. We test both methods on the
      Clancy and Rudy (2002) I(Na)Markov chain model. With precomputed tables for
      functions of the transmembrane voltage, both methods are comparable to the
      forward Euler method in accuracy and computational cost, but allow longer time
      steps without numerical instability. We conclude that both methods are of
      practical interest. MRL requires more computations than HOS, but is formulated in
      general terms which can be readily extended to other Markov chain channel models,
      whereas the utility of HOS depends on the asymptotic properties of a particular
      model. The significance of the methods is that they allow a considerable speed-up
      of large-scale computations of cardiac excitation models by increasing the time
      step, while maintaining acceptable accuracy and preserving numerical stability.

PMID- 25376031
TI  - In vivo and in vitro comparison of the charge injection capacity of platinum
      macroelectrodes.
AB  - Platinum (Pt) is the most commonly used metal for stimulating electrodes. This
      study aims to determine the amount of charge that can be delivered without
      causing irreversible electrochemical reactions (charge injection capacity, Q inj)
      of Pt macroelectrodes (geometric surface area >0.001 cm(2)) in vitro and in vivo
      using voltage transient measurements. Pt macroelectrodes were stimulated with
      biphasic charge-balanced cathodic-first constant-current pulses in phosphate
      buffered saline. Potential excursions were measured (versus Ag/AgCl electrode)
      and used to determine Qinj. The in vitro Qinj were compared to those measured in
      vivo following: acute and chronic implantation close to the retina; chronic
      intracochlear implantation; and acute subdural implantation, in the cat. Qinj
      increased with pulsewidth from 35 to 54 MUC/cm(2) for respective pulse widths of
      100 to 3200 MUs per phase in vitro. Qinj was significantly less in vivo. There
      was no significant difference in Qinj between acutely (3.84 to 16.6 MUC/cm(2)
      with pulsewidths of 100 to 3200 MUs) and chronically (6.99 to 15.8 MUC/cm(2) with
      pulsewidths of 200 to 3200 MUs) implanted suprachoroidal electrodes.
      Intracochlear Qinj was not different to suprachoroidal Qinj, while subdural Qinj
      was significantly less than the suprachoroidal Q inj (p < 0.05). These results
      have important implications in providing guidelines on Qinj for the safe use of
      Pt stimulating macroelectrodes and question the relevance of measuring Qinj in
      vivo using voltage transients.

PMID- 25376032
TI  - Quantifying electrode reliability during brain-computer interface operation.
AB  - One of the problems of noninvasive brain-computer interface (BCI) applications is
      the occurrence of anomalous (unexpected) signals that might degrade BCI
      performance. This situation might slip the operator's attention since raw signals
      are not usually continuously visualized and monitored during BCI-actuated device
      operation. Anomalous data can for instance be the result of electrode
      misplacement, degrading impedance or loss of connectivity. Since this problem can
      develop at run time, there is a need of a systematic approach to evaluate
      electrode reliability during online BCI operation. In this paper, we propose two
      metrics detecting how much each channel is deviating from its expected behavior.
      This quantifies electrode reliability at run time which could be embedded into
      BCI data processing to increase performance. We assess the effectiveness of these
      metrics in quantifying signal degradation by conducting three experiments:
      Electrode swap, electrode manipulation, and offline artificially degradation of
      P300 signals. 

PMID- 25376033
TI  - Doppler radar fall activity detection using the wavelet transform.
AB  - We propose in this paper the use of Wavelet transform (WT) to detect human falls
      using a ceiling mounted Doppler range control radar. The radar senses any motions
      from falls as well as nonfalls due to the Doppler effect. The WT is very
      effective in distinguishing the falls from other activities, making it a
      promising technique for radar fall detection in nonobtrusive inhome elder care
      applications. The proposed radar fall detector consists of two stages. The
      prescreen stage uses the coefficients of wavelet decomposition at a given scale
      to identify the time locations in which fall activities may have occurred. The
      classification stage extracts the time-frequency content from the wavelet
      coefficients at many scales to form a feature vector for fall versus nonfall
      classification. The selection of different wavelet functions is examined to
      achieve better performance. Experimental results using the data from the
      laboratory and real inhome environments validate the promising and robust
      performance of the proposed detector. 

PMID- 25376034
TI  - A microwave imaging-based technique to localize an in-body RF source for
      biomedical applications.
AB  - In some biomedical applications such as wireless capsule endoscopy, the
      localization of an in-body radio-frequency (RF) source is important for the
      positioning of any abnormality inside the gastrointestinal tract. With knowledge
      of the location, therapeutic operations can be performed precisely at the
      position of the abnormality. Electrical properties (relative permittivity and
      conductivity) of the tissues and their distribution are utilized to estimate the
      position. This paper presents a method for the localization of an in-body RF
      source based on microwave imaging. The electrical properties of the tissues and
      their distribution at 403.5 MHz are found from microwave imaging and the position
      of an RF source is then estimated based on the image. The method is applied on
      synthetic noisy data, obtained after the addition of white Gaussian noise to
      simulated data of a simple circular phantom, and a realistic phantom in a 2-D
      case. The root-mean-square of the error distance between the actual and the
      estimated position is found to be within 10 and 4 mm for the circular and the
      realistic phantom, respectively, showing the capability of the proposed algorithm
      to work with a good accuracy even in the presence of noise for the localization
      of the in-body RF source. 

PMID- 25376035
TI  - Robotic system for MRI-guided stereotactic neurosurgery.
AB  - Stereotaxy is a neurosurgical technique that can take several hours to reach a
      specific target, typically utilizing a mechanical frame and guided by
      preoperative imaging. An error in any one of the numerous steps or deviations of
      the target anatomy from the preoperative plan such as brain shift (up to mm), may
      affect the targeting accuracy and thus the treatment effectiveness. Moreover,
      because the procedure is typically performed through a small burr hole opening in
      the skull that prevents tissue visualization, the intervention is basically
      "blind" for the operator with limited means of intraoperative confirmation that
      may result in reduced accuracy and safety. The presented system is intended to
      address the clinical needs for enhanced efficiency, accuracy, and safety of image
      guided stereotactic neurosurgery for deep brain stimulation lead placement. The
      study describes a magnetic resonance imaging (MRI)-guided, robotically actuated
      stereotactic neural intervention system for deep brain stimulation procedure,
      which offers the potential of reducing procedure duration while improving
      targeting accuracy and enhancing safety. This is achieved through simultaneous
      robotic manipulation of the instrument and interactively updated in situ MRI
      guidance that enables visualization of the anatomy and interventional instrument.
      During simultaneous actuation and imaging, the system has demonstrated less than
      15% signal-to-noise ratio variation and less than 0.20 geometric distortion
      artifact without affecting the imaging usability to visualize and guide the
      procedure. Optical tracking and MRI phantom experiments streamline the clinical
      workflow of the prototype system, corroborating targeting accuracy with three-ax-
      s root mean square error 1.38 +/- 0.45 mm in tip position and 2.03 +/- 0.58
      degrees  in insertion angle.

PMID- 25376036
TI  - Transfer learning improves supervised image segmentation across imaging
      protocols.
AB  - The variation between images obtained with different scanners or different
      imaging protocols presents a major challenge in automatic segmentation of
      biomedical images. This variation especially hampers the application of otherwise
      successful supervised-learning techniques which, in order to perform well, often
      require a large amount of labeled training data that is exactly representative of
      the target data. We therefore propose to use transfer learning for image
      segmentation. Transfer-learning techniques can cope with differences in
      distributions between training and target data, and therefore may improve
      performance over supervised learning for segmentation across scanners and scan
      protocols. We present four transfer classifiers that can train a classification
      scheme with only a small amount of representative training data, in addition to a
      larger amount of other training data with slightly different characteristics. The
      performance of the four transfer classifiers was compared to that of standard
      supervised classification on two magnetic resonance imaging brain-segmentation
      tasks with multi-site data: white matter, gray matter, and cerebrospinal fluid
      segmentation; and white-matter-/MS-lesion segmentation. The experiments showed
      that when there is only a small amount of representative training data available,
      transfer learning can greatly outperform common supervised-learning approaches,
      minimizing classification errors by up to 60%. 

PMID- 25376037
TI  - FPGA-based voltage and current dual drive system for high frame rate electrical
      impedance tomography.
AB  - Electrical impedance tomography (EIT) is used to image the electrical property
      distribution of a tissue under test. An EIT system comprises complex hardware and
      software modules, which are typically designed for a specific application.
      Upgrading these modules is a time-consuming process, and requires rigorous
      testing to ensure proper functioning of new modules with the existing ones. To
      this end, we developed a modular and reconfigurable data acquisition (DAQ) system
      using National Instruments' (NI) hardware and software modules, which offer
      inherent compatibility over generations of hardware and software revisions. The
      system can be configured to use up to 32-channels. This EIT system can be used to
      interchangeably apply current or voltage signal, and measure the tissue response
      in a semi-parallel fashion. A novel signal averaging algorithm, and 512-point
      fast Fourier transform (FFT) computation block was implemented on the FPGA. FFT
      output bins were classified as signal or noise. Signal bins constitute a tissue's
      response to a pure or mixed tone signal. Signal bins' data can be used for
      traditional applications, as well as synchronous frequency-difference imaging.
      Noise bins were used to compute noise power on the FPGA. Noise power represents a
      metric of signal quality, and can be used to ensure proper tissue-electrode
      contact. Allocation of these computationally expensive tasks to the FPGA reduced
      the required bandwidth between PC, and the FPGA for high frame rate EIT. In 16
      channel configuration, with a signal-averaging factor of 8, the DAQ frame rate at
      100 kHz exceeded 110 frames s (-1), and signal-to-noise ratio exceeded 90 dB
      across the spectrum. Reciprocity error was found to be for frequencies up to 1
      MHz. Static imaging experiments were performed on a high-conductivity inclusion
      placed in a saline filled tank; the inclusion was clearly localized in the
      reconstructions obtained for both absolute current and voltage mode data. 

PMID- 25376038
TI  - Hybrid approaches for interactive image segmentation using the live markers
      paradigm.
AB  - Interactive image segmentation methods normally rely on cues about the foreground
      imposed by the user as region constraints (markers/brush strokes) or boundary
      constraints (anchor points). These paradigms often have complementary strengths
      and weaknesses, which can be addressed to improve the interactive experience by
      reducing the user's effort. We propose a novel hybrid paradigm based on a new
      form of interaction called live markers, where optimum boundary-tracking segments
      are turned into internal and external markers for region-based delineation to
      effectively extract the object. We present four techniques within this paradigm:
      1) LiveMarkers; 2) RiverCut; 3) LiveCut; and 4) RiverMarkers. The homonym
      LiveMarkers couples boundary-tracking via live-wire-on-the-fly (LWOF) with
      optimum seed competition by the image foresting transform (IFT-SC). The IFT-SC
      can cope with complex object silhouettes, but presents a leaking problem on
      weaker parts of the boundary that is solved by the effective live markers
      produced by LWOF. Conversely, in RiverCut, the long boundary segments computed by
      Riverbed around complex shapes provide markers for Graph Cuts by the Min-Cut/Max
      Flow algorithm (GCMF) to complete segmentation on poorly defined sections of the
      object's border. LiveCut and RiverMarkers further demonstrate that live markers
      can improve segmentation even when the combined approaches are not complementary
      (e.g., GCMFs shrinking bias is also dramatically prevented when using it with
      LWOF). Moreover, since delineation is always region based, our methodology
      subsumes both paradigms, representing a new way of extending boundary tracking to
      the 3D image domain, while speeding up the addition of markers close to the
      object's boundary-a necessary but time consuming task when done manually. We
      justify our claims through an extensive experimental evaluation on natural and
      medical images data sets, using recently proposed robot users for boundary
      tracking methods.

PMID- 25376039
TI  - Optimal design of multichannel equalizers for the structural similarity index.
AB  - The optimization of multichannel equalizers is studied for the structural
      similarity (SSIM) criteria. The closed-form formula is provided for the optimal
      equalizer when the mean of the source is zero. The formula shows that the
      equalizer with maximal SSIM index is equal to the one with minimal mean square
      error (MSE) multiplied by a positive real number, which is shown to be equal to
      the inverse of the achieved SSIM index. The relation of the maximal SSIM index to
      the minimal MSE is also established for given blurring filters and fixed length
      equalizers. An algorithm is also presented to compute the suboptimal equalizer
      for the general sources. Various numerical examples are given to demonstrate the
      effectiveness of the results.

PMID- 25376040
TI  - Symmetric subspace learning for image analysis.
AB  - Subspace learning (SL) is one of the most useful tools for image analysis and
      recognition. A large number of such techniques have been proposed utilizing a
      priori knowledge about the data. In this paper, new subspace learning techniques
      are presented that use symmetry constraints in their objective functions. The
      rational behind this idea is to exploit the a priori knowledge that geometrical
      symmetry appears in several types of data, such as images, objects, faces, and so
      on. Experiments on artificial, facial expression recognition, face recognition,
      and object categorization databases highlight the superiority and the robustness
      of the proposed techniques, in comparison with standard SL techniques.

PMID- 25376041
TI  - Quantitative evaluation of a low-cost noninvasive hybrid interface based on EEG
      and eye movement.
AB  - This paper describes a low-cost noninvasive brain-computer interface (BCI)
      hybridized with eye tracking. It also discusses its feasibility through a Fitts'
      law-based quantitative evaluation method. Noninvasive BCI has recently received a
      lot of attention. To bring the BCI applications into real life, user-friendly and
      easily portable devices need to be provided. In this work, as an approach to
      realize a real-world BCI, electroencephalograph (EEG)-based BCI combined with eye
      tracking is investigated. The two interfaces can be complementary to attain
      improved performance. Especially to consider public availability, a low-cost
      interface device is intentionally used for test. A low-cost commercial EEG
      recording device is integrated with an inexpensive custom-built eye tracker. The
      developed hybrid interface is evaluated through target pointing and selection
      experiments. Eye movement is interpreted as cursor movement and noninvasive BCI
      selects a cursor point with two selection confirmation schemes. Using Fitts' law,
      the proposed interface scheme is compared with other interface schemes such as
      mouse, eye tracking with dwell time, and eye tracking with keyboard. In addition,
      the proposed hybrid BCI system is discussed with respect to a practical interface
      scheme. Although further advancement is required, the proposed hybrid BCI system
      has the potential to be practically useful in a natural and intuitive manner. 

PMID- 25376042
TI  - Design of Endoscopic Capsule With Multiple Cameras.
AB  - In order to reduce the miss rate of the wireless capsule endoscopy, in this
      paper, we propose a new system of the endoscopic capsule with multiple cameras. A
      master-slave architecture, including an efficient bus architecture and a four
      level clock management architecture, is applied for the Multiple Cameras
      Endoscopic Capsule (MCEC). For covering more area of the gastrointestinal tract
      wall with low power, multiple cameras with a smart image capture strategy,
      including movement sensitive control and camera selection, are used in the MCEC.
      To reduce the data transfer bandwidth and power consumption to prolong the MCEC's
      working life, a low complexity image compressor with PSNR 40.7 dB and compression
      rate 86% is implemented. A chipset is designed and implemented for the MCEC and a
      six cameras endoscopic capsule prototype is implemented by using the chipset.
      With the smart image capture strategy, the coverage rate of the MCEC prototype
      can achieve 98% and its power consumption is only about 7.1 mW.

PMID- 25376043
TI  - Properties and Performance of Imperfect Dual Neural Network-Based kWTA Networks.
AB  - The dual neural network (DNN)-based k -winner-take-all ( k WTA) model is an
      effective approach for finding the k largest inputs from n inputs. Its major
      assumption is that the threshold logic units (TLUs) can be implemented in a
      perfect way. However, when differential bipolar pairs are used for implementing
      TLUs, the transfer function of TLUs is a logistic function. This brief studies
      the properties of the DNN- kWTA model under this imperfect situation. We prove
      that, given any initial state, the network settles down at the unique equilibrium
      point. Besides, the energy function of the model is revealed. Based on the energy
      function, we propose an efficient method to study the model performance when the
      inputs are with continuous distribution functions. Furthermore, for uniformly
      distributed inputs, we derive a formula to estimate the probability that the
      model produces the correct outputs. Finally, for the case that the minimum
      separation ?min of the inputs is given, we prove that if the gain of the
      activation function is greater than 1/4?min max(ln 2n, 2 ln 1 - epsilon/epsilon
      ), then the network can produce the correct outputs with winner outputs greater
      than 1-epsilon and loser outputs less than epsilon, where epsilon is the
      threshold less than 0.5.

PMID- 25376044
TI  - A Unified Framework for Data Visualization and Coclustering.
AB  - We propose a new theoretical framework for data visualization. This framework is
      based on iterative procedure looking up an appropriate approximation of the data
      matrix A by using two stochastic similarity matrices from the set of rows and the
      set of columns. This process converges to a steady state where the approximated
      data A is composed of g similar rows and l similar columns. Reordering A
      according to the first left and right singular vectors involves an optimal data
      reorganization revealing homogeneous block clusters. Furthermore, we show that
      our approach is related to a Markov chain model, to the double k-means with g *l
      block clusters and to a spectral coclustering. Numerical experiments on simulated
      and real data sets show the interest of our approach.

PMID- 25376045
TI  - An Improved TA-SVM Method Without Matrix Inversion and Its Fast Implementation
      for Nonstationary Datasets.
AB  - Recently, a time-adaptive support vector machine (TA-SVM) is proposed for
      handling nonstationary datasets. While attractive performance has been reported
      and the new classifier is distinctive in simultaneously solving several SVM
      subclassifiers locally and globally by using an elegant SVM formulation in an
      alternative kernel space, the coupling of subclassifiers brings in the
      computation of matrix inversion, thus resulting to suffer from high computational
      burden in large nonstationary dataset applications. To overcome this shortcoming,
      an improved TA-SVM (ITA-SVM) is proposed using a common vector shared by all the
      SVM subclassifiers involved. ITA-SVM not only keeps an SVM formulation, but also
      avoids the computation of matrix inversion. Thus, we can realize its fast
      version, that is, improved time-adaptive core vector machine (ITA-CVM) for large
      nonstationary datasets by using the CVM technique. ITA-CVM has the merit of
      asymptotic linear time complexity for large nonstationary datasets as well as
      inherits the advantage of TA-SVM. The effectiveness of the proposed classifiers
      ITA-SVM and ITA-CVM is also experimentally confirmed. 

PMID- 25376046
TI  - Context Dependent Encoding Using Convolutional Dynamic Networks.
AB  - Perception of sensory signals is strongly influenced by their context, both in
      space and time. In this paper, we propose a novel hierarchical model, called
      convolutional dynamic networks, that effectively utilizes this contextual
      information, while inferring the representations of the visual inputs. We build
      this model based on a predictive coding framework and use the idea of empirical
      priors to incorporate recurrent and top-down connections. These connections endow
      the model with contextual information coming from temporal as well as abstract
      knowledge from higher layers. To perform inference efficiently in this
      hierarchical model, we rely on a novel scheme based on a smoothing proximal
      gradient method. When trained on unlabeled video sequences, the model learns a
      hierarchy of stable attractors, representing low-level to high-level parts of the
      objects. We demonstrate that the model effectively utilizes contextual
      information to produce robust and stable representations for object recognition
      in video sequences, even in case of highly corrupted inputs. 

PMID- 25376047
TI  - MTC: A Fast and Robust Graph-Based Transductive Learning Method.
AB  - Despite the great success of graph-based transductive learning methods, most of
      them have serious problems in scalability and robustness. In this paper, we
      propose an efficient and robust graph-based transductive classification method,
      called minimum tree cut (MTC), which is suitable for large-scale data. Motivated
      from the sparse representation of graph, we approximate a graph by a spanning
      tree. Exploiting the simple structure, we develop a linear-time algorithm to
      label the tree such that the cut size of the tree is minimized. This
      significantly improves graph-based methods, which typically have a polynomial
      time complexity. Moreover, we theoretically and empirically show that the
      performance of MTC is robust to the graph construction, overcoming another big
      problem of traditional graph-based methods. Extensive experiments on public data
      sets and applications on web-spam detection and interactive image segmentation
      demonstrate our method's advantages in aspect of accuracy, speed, and robustness.

PMID- 25376048
TI  - Multimodality Neurological Data Visualization With Multi-VOI-Based DTI Fiber
      Dynamic Integration.
AB  - Brain lesions are usually located adjacent to critical spinal structures, so it
      is a challenging task for neurosurgeons to precisely plan a surgical procedure
      without damaging healthy tissues and nerves. The advancement of medical imaging
      technologies produces a large amount of neurological data, which are capable of
      showing a wide variety of brain properties. Advanced algorithms of medical data
      computing and visualization are critically helpful in efficiently utilizing the
      acquired data for disease diagnosis and brain function and structure exploration,
      which is helpful for treatment planning. In this paper, we describe new
      algorithms and a software framework for multiple volume of interest specified
      diffusion tensor imaging (DTI) fiber dynamic visualization. The displayed results
      have been integrated with a volume rendering pipeline for multimodality
      neurological data exploration. A depth texture indexing algorithm is used to
      detect DTI fiber tracts in graphics process units (GPUs), which makes fibers to
      be displayed and interactively manipulated with brain data acquired from
      functional magnetic resonance imaging, T1- and T2-weighted anatomic imaging, and
      angiographic imaging. The developed software platform is built on an object
      oriented structure, which is transparent and extensible. It provides a
      comprehensive human-computer interface for data exploration and information
      extraction. The GPU-accelerated high-performance computing kernels have been
      implemented to enable our software to dynamically visualize neurological data.
      The developed techniques will be useful in computer-aided neurological disease
      diagnosis, brain structure exploration, and general cognitive neuroscience.

PMID- 25376049
TI  - Single-Trial Visual Evoked Potential Extraction Using Partial Least-Squares-Based
      Approach.
AB  - A single-trial extraction of a visual evoked potential (VEP) signal based on the
      partial least-squares (PLS) regression method has been proposed in this paper.
      This paper has focused on the extraction and estimation of the latencies of P100,
      P200, P300, N75, and N135 in the artificial electroencephalograph (EEG) signal.
      The real EEG signal obtained from the hospital was only concentrated on the P100.
      The performance of the PLS has been evaluated mainly on the basis of latency
      error rate of the peaks for the artificial EEG signal, and the mean peak
      detection and standard deviation for the real EEG signal. The simulation results
      show that the proposed PLS algorithm is capable of reconstructing the EEG signal
      into its desired shape of the ideal VEP. For P100, the proposed PLS algorithm is
      able to provide comparable results to the generalized eigenvalue decomposition
      (GEVD) algorithm, which alters (prewhitens) the EEG input signal using the
      prestimulation EEG signal. It has also shown better performance for later peaks
      (P200 and P300). The PLS outperformed not only in positive peaks but also in N75.
      In P100, the PLS was comparable with the GEVD although N135 was better estimated
      by GEVD. The proposed PLS algorithm is comparable to GEVD given that PLS does not
      alter the EEG input signal. The PLS algorithm gives the best estimate to
      multitrial ensemble averaging. This research offers benefits such as avoiding
      patient's fatigue during VEP test measurement in the hospital, in BCI
      applications and in EEG-fMRI integration. 

PMID- 25376050
TI  - A Multirobot Path-Planning Strategy for Autonomous Wilderness Search and Rescue.
AB  - This paper presents a novel strategy for the on-line planning of optimal motion
      paths for a team of autonomous ground robots engaged in wilderness search and
      rescue (WiSAR). The proposed strategy, which forms part of an overall multirobot
      coordination (MRC) methodology, addresses the dynamic nature of WiSAR by: 1)
      planning initial, time-optimal, and piecewise polynomial paths for all robots; 2)
      implementing and regularly evaluating the optimality of the paths through a set
      of checks that gauge feasibility of path-completion within the available time;
      and 3) replanning paths, on-line, whenever deemed necessary. The fundamental
      principle of maintaining the optimal deployment of the robots throughout the
      search guides the MRC methodology. The proposed path-planning strategy is
      illustrated through a simulated realistic WiSAR example, and compared to an
      alternative, nonprobabilistic approach. 

PMID- 25376051
TI  - Scene Parsing From an MAP Perspective.
AB  - Scene parsing is an important problem in the field of computer vision. Though
      many existing scene parsing approaches have obtained encouraging results, they
      fail to overcome within-category inconsistency and intercategory similarity of
      superpixels. To reduce the aforementioned problem, a novel method is proposed in
      this paper. The proposed approach consists of three main steps: 1) posterior
      category probability density function (PDF) is learned by an efficient low-rank
      representation classifier (LRRC); 2) prior contextual constraint PDF on the map
      of pixel categories is learned by Markov random fields; and 3) final parsing
      results are yielded up to the maximum a posterior process based on the two
      learned PDFs. In this case, the nature of being both dense for within-category
      affinities and almost zeros for intercategory affinities is integrated into our
      approach by using LRRC to model the posterior category PDF. Meanwhile, the
      contextual priori generated by modeling the prior contextual constraint PDF helps
      to promote the performance of scene parsing. Experiments on benchmark datasets
      show that the proposed approach outperforms the state-of-the-art approaches for
      scene parsing. 

PMID- 25376052
TI  - Robust Frequency-Domain Constrained Feedback Design via a Two-Stage Heuristic
      Approach.
AB  - Based on a two-stage heuristic method, this paper is concerned with the design of
      robust feedback controllers with restricted frequency-domain specifications
      (RFDSs) for uncertain linear discrete-time systems. Polytopic uncertainties are
      assumed to enter all the system matrices, while RFDSs are motivated by the fact
      that practical design specifications are often described in restricted finite
      frequency ranges. Dilated multipliers are first introduced to relax the
      generalized Kalman-Yakubovich-Popov lemma for output feedback controller
      synthesis and robust performance analysis. Then a two-stage approach to output
      feedback controller synthesis is proposed: at the first stage, a robust full
      information (FI) controller is designed, which is used to construct a required
      output feedback controller at the second stage. To improve the solvability of the
      synthesis method, heuristic iterative algorithms are further formulated for
      exploring the feedback gain and optimizing the initial FI controller at the
      individual stage. The effectiveness of the proposed design method is finally
      demonstrated by the application to active control of suspension systems. 

PMID- 25376054
TI  - Do orgasms give women feedback about mate choice?
AB  - The current study represents a preliminary investigation of the extent to which
      female orgasm functions to promote good mate choices. Based on a survey of
      heterosexual female college students in committed relationships, how often women
      experienced orgasm as a result of sexual intercourse was related to their
      partner's family income, his self-confidence, and how attractive he was. Orgasm
      intensity was also related to how attracted they were to their partners, how many
      times they had sex per week, and ratings of sexual satisfaction. Those with
      partners who their friends rated as more attractive also tended to have more
      intense orgasms. Orgasm frequency was highly correlated (r = .82) with orgasm
      intensity, and orgasm intensity was a marginally better predictor of sexual
      satisfaction than orgasm frequency. Sexual satisfaction was related to how
      physically attracted women were to their partner and the breadth of his
      shoulders. Women who began having sexual intercourse at earlier ages had more sex
      partners, experienced more orgasms, and were more sexually satisfied with their
      partners. We also identified an ensemble of partner psychological traits
      (motivation, intelligence, focus, and determination) that predicted how often
      women initiated sexual intercourse. Their partner's sense of humor not only
      predicted his self-confidence and family income, but it also predicted women's
      propensity to initiate sex, how often they had sex, and it enhanced their orgasm
      frequency in comparison with other partners. 

PMID- 25376055
TI  - Expanded access to non-VA care through the Veterans Choice Program. Interim final
      rule.
AB  - The Department of Veterans Affairs (VA) amends its medical regulations concerning
      its authority for eligible veterans to receive care from non-VA entities and
      providers. The Veterans Access, Choice, and Accountability Act of 2014 directs VA
      to establish a program to furnish hospital care and medical services through non
      VA health care providers to veterans who either cannot be seen within the wait
      time goals of the Veterans Health Administration or who qualify based on their
      place of residence (hereafter referred to as the Veterans Choice Program, or the
      ''Program''). The law also requires VA to publish an interim final rule
      establishing this program. This interim final rule defines the parameters of the
      Veterans Choice Program, and clarifies aspects affecting veterans and the non-VA
      providers who will furnish hospital care and medical services through the
      Veterans Choice Program.

PMID- 25376053
TI  - Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic
      Factors that Influence Benzene-Induced Genotoxicity.
AB  - BACKGROUND: Inhalation of benzene at levels below the current exposure limit
      values leads to hematotoxicity in occupationally exposed workers. OBJECTIVE: We
      sought to evaluate Diversity Outbred (DO) mice as a tool for exposure threshold
      assessment and to identify genetic factors that influence benzene-induced
      genotoxicity. METHODS: We exposed male DO mice to benzene (0, 1, 10, or 100 ppm;
      75 mice/exposure group) via inhalation for 28 days (6 hr/day for 5 days/week).
      The study was repeated using two independent cohorts of 300 animals each. We
      measured micronuclei frequency in reticulocytes from peripheral blood and bone
      marrow and applied benchmark concentration modeling to estimate exposure
      thresholds. We genotyped the mice and performed linkage analysis. RESULTS: We
      observed a dose-dependent increase in benzene-induced chromosomal damage and
      estimated a benchmark concentration limit of 0.205 ppm benzene using DO mice.
      This estimate is an order of magnitude below the value estimated using B6C3F1
      mice. We identified a locus on Chr 10 (31.87 Mb) that contained a pair of
      overexpressed sulfotransferases that were inversely correlated with genotoxicity.
      CONCLUSIONS: The genetically diverse DO mice provided a reproducible response to
      benzene exposure. The DO mice display interindividual variation in toxicity
      response and, as such, may more accurately reflect the range of response that is
      observed in human populations. Studies using DO mice can localize genetic
      associations with high precision. The identification of sulfotransferases as
      candidate genes suggests that DO mice may provide additional insight into benzene
      induced genotoxicity.

PMID- 25376057
TI  - Splenosis mimicking hepatocellular carcinoma.

PMID- 25376056
TI  - Medicare and Medicaid programs; CY 2015 Home Health Prospective Payment System
      rate update; Home Health Quality Reporting Requirements; and survey and
      enforcement requirements for home health agencies. Final rule.
AB  - This final rule updates Home Health Prospective Payment System (HH PPS) rates,
      including the national, standardized 60-day episode payment rates, the national
      per-visit rates, and the non-routine medical supply (NRS) conversion factor under
      the Medicare prospective payment system for home health agencies (HHAs),
      effective for episodes ending on or after January 1, 2015. As required by the
      Affordable Care Act, this rule implements the second year of the four-year phase
      in of the rebasing adjustments to the HH PPS payment rates. This rule provides
      information on our efforts to monitor the potential impacts of the rebasing
      adjustments and the Affordable Care Act mandated face-to-face encounter
      requirement. This rule also implements: Changes to simplify the face-to-face
      encounter regulatory requirements; changes to the HH PPS case-mix weights;
      changes to the home health quality reporting program requirements; changes to
      simplify the therapy reassessment timeframes; a revision to the Speech-Language
      Pathology (SLP) personnel qualifications; minor technical regulations text
      changes; and limitations on the reviewability of the civil monetary penalty
      provisions. Finally, this rule also discusses Medicare coverage of insulin
      injections under the HH PPS, the delay in the implementation of the International
      Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM),
      and a HH value-based purchasing (HH VBP) model.

PMID- 25376058
TI  - Medicare program; End-Stage Renal Disease prospective payment system, quality
      incentive program, and Durable Medical Equipment, Prosthetics, Orthotics, and
      Supplies. Final rule.
AB  - This final rule will update and make revisions to the End-Stage Renal Disease
      (ESRD) prospective payment system (PPS) for calendar year (CY) 2015. This rule
      also finalizes requirements for the ESRD quality incentive program (QIP),
      including for payment years (PYs) 2017 and 2018. This rule will also make a
      technical correction to remove outdated terms and definitions. In addition, this
      final rule sets forth the methodology for adjusting Durable Medical Equipment,
      Prosthetics, Orthotics, and Supplies (DMEPOS) fee schedule payment amounts using
      information from the Medicare DMEPOS Competitive Bidding Program (CBP); makes
      alternative payment rules for certain DME under the Medicare DMEPOS CBP;
      clarifies the statutory Medicare hearing aid coverage exclusion and specifies
      devices not subject to the hearing aid exclusion; will not update the definition
      of minimal self-adjustment; clarifies the Change of Ownership (CHOW) and provides
      for an exception to the current requirements; revises the appeal provisions for
      termination of a CBP contract, including the beneficiary notification requirement
      under the Medicare DMEPOS CBP, and makes a technical change to the regulation
      related to the conditions for awarding contracts for furnishing infusion drugs
      under the Medicare DMEPOS CBP.

PMID- 25376059
TI  - Is initial cholecystectomy is an optimal strategy for patients with suspected
      choledocholithiasis?

PMID- 25376060
TI  - Bringing it to the community: successful programs that increase the use of
      clinical preventive services by vulnerable older populations.
AB  - This policy brief reports the findings of a systematic review conducted by the
      Community Health Innovations in Prevention for Seniors (CHIPS) project. The
      project identified successful programs for increasing the use of two or more
      clinical preventive services for vulnerable, underserved populations ages 50
      years and older within community settings. The CHIPS project also used the RE-AIM
      Framework to evaluate the readiness and feasibility of implementing these
      programs within real-world settings. Policy recommendations focus on expanding
      and sustaining clinical preventive services in the community and reaching diverse
      populations, bridging the traditional silos of clinical care and community-based
      services, and providing financial incentives to clinical providers and community
      based organizations to support preventive services coverage.

PMID- 25376061
TI  - Increased service use following Medicaid expansion is mostly temporary: evidence
      from California's low income health program.
AB  - The Affordable Care Act (ACA) has already resulted in expanded eligibility for
      Medicaid in 27 states, including California, as of 2014. One major concern about
      the Medicaid expansion is that a high level of need among the newly eligible may
      lead to runaway costs, which could overwhelm state budgets when federal subsidies
      no longer cover 100 percent of the expansion population's costs in 2017. Although
      cost increases as a result of the newly eligible are likely, an even more
      important question is whether these increases will be temporary or permanent.
      Evidence from California's Low Income Health Program (LIHP) suggests that cost
      and utilization increases among newly eligible Medicaid beneficiaries will be
      mostly temporary. This policy brief presents data showing a significant decline
      in the use of hospital inpatient care and in emergency room visits after one year
      of enrollment in LIHP, and a stable, not increasing, rate of outpatient service
      use. Because LIHP provided health care coverage from 2011 to 2013 in advance of
      the full Medicaid expansion, our findings suggest that early and significant
      investments in infrastructure and in improving the process of care delivery can
      effectively address the pent-up demand for health care services of previously
      uninsured populations.

PMID- 25376062
TI  - It's time to get mad about the outrageous cost of health care: why it's so high,
      how it affects your wallet--and yes, what you can do about it.

PMID- 25376063
TI  - Maintaining the momentum of change: the role of the 2014 updates to the
      compendium in preventing healthcare-associated infections.
AB  - Preventing healthcare-associated infections (HAIs) is a national priority.
      Although substantial progress has been achieved, considerable deficiencies remain
      in our ability to efficiently and effectively translate existing knowledge about
      HAI prevention into reliable, sustainable, widespread practice. "A Compendium of
      Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals:
      2014 Updates" is the product of a highly collaborative endeavor designed to
      support hospitals' efforts to implement and sustain HAI prevention strategies.

PMID- 25376065
TI  - An infection preventionist's view of the compendium of strategies to prevent
      healthcare-associated infections: structure, process, and outcome.

PMID- 25376064
TI  - Approaches for preventing healthcare-associated infections: go long or go wide?

PMID- 25376066
TI  - A view from The Joint Commission perspective: updated compendium will continue to
      help reduce healthcare-associated infections.

PMID- 25376067
TI  - A compendium of strategies to prevent healthcare-associated infections in acute
      care hospitals: 2014 updates.
AB  - Since the publication of "A Compendium of Strategies to Prevent Healthcare
      Associated Infections in Acute Care Hospitals" in 2008, prevention of healthcare
      associated infections (HAIs) has become a national priority. Despite
      improvements, preventable HAIs continue to occur. The 2014 updates to the
      Compendium were created to provide acute care hospitals with up-to-date,
      practical, expert guidance to assist in prioritizing and implementing their HAI
      prevention efforts. They are the product of a highly collaborative effort led by
      the Society for Healthcare Epidemiology of America (SHEA), the Infectious
      Diseases Society of America (IDSA), the American Hospital Association (AHA), the
      Association for Professionals in Infection Control and Epidemiology (APIC), and
      The Joint Commission, with major contributions from representatives of a number
      of organizations and societies with content expertise, including the Centers for
      Disease Control and Prevention (CDC), the Institute for Healthcare Improvement
      (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical
      Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical
      Infection Society (SIS).

PMID- 25376068
TI  - Strategies to prevent catheter-associated urinary tract infections in acute care
      hospitals: 2014 update.

PMID- 25376069
TI  - Strategies to prevent Clostridium difficile infections in acute care hospitals:
      2014 update.

PMID- 25376070
TI  - Strategies to prevent surgical site infections in acute care hospitals: 2014
      update.

PMID- 25376071
TI  - Strategies to prevent central line-associated bloodstream infections in acute
      care hospitals: 2014 update.

PMID- 25376072
TI  - Strategies to prevent methicillin-resistant Staphylococcus aureus transmission
      and infection in acute care hospitals: 2014 update.

PMID- 25376073
TI  - Strategies to prevent ventilator-associated pneumonia in acute care hospitals:
      2014 update.

PMID- 25376074
TI  - Strategies to prevent healthcare-associated infections through hand hygiene.

PMID- 25376075
TI  - More than 'surviving'--thriving.

PMID- 25376076
TI  - Fighting the fire.

PMID- 25376077
TI  - Caring for the inside.

PMID- 25376078
TI  - No brittle bones.

PMID- 25376079
TI  - Conquering cancer.

PMID- 25376080
TI  - Keeping your brain sharp.

PMID- 25376081
TI  - Brightening the blues.

PMID- 25376082
TI  - Nurturing your spirit.

PMID- 25376083
TI  - Disposition of ampicillin trihydrate in plasma, uterine tissue, lochial fluid,
      and milk of postpartum dairy cattle.
AB  - The objective of this study was to determine the disposition of ampicillin in
      plasma, uterine tissue, lochial fluid, and milk of postpartum dairy cattle.
      Ampicillin trihydrate was administered by intramuscular (i.m.) injection at a
      dose of 11 mg/kg of body weight every 24 h (n = 6, total of 3 doses) or every 12
      h (n = 6, total of 5 doses) for 3 days. Concentrations of ampicillin were
      measured in plasma, uterine tissue, lochial fluid, and milk using HPLC with
      ultraviolet absorption. Quantifiable ampicillin concentrations were found in
      plasma, milk, and lochial fluid of all cattle within 30 min, 4 h, and 4 h of
      administration of ampicillin trihydrate, respectively. There was no significant
      effect of dosing interval (every 12 vs. every 24 h) and no significant
      interactions between dosing interval and sampling site on the pharmacokinetic
      variable measured or calculated. Median peak ampicillin concentration at steady
      state was significantly higher in lochial fluid (5.27 MUg/mL after q 24 h dosing)
      than other body fluids or tissues and significantly higher in plasma (3.11
      MUg/mL) compared to milk (0.49 MUg/mL) or endometrial tissue (1.55 MUg/mL).
      Ampicillin trihydrate administered once daily by the i.m. route at the label dose
      of 11 mg/kg of body weight achieves therapeutic concentrations in the milk,
      lochial fluid, and endometrial tissue of healthy postpartum dairy cattle.

PMID- 25376084
TI  - Factors influencing the use of intensive procedures at the end of life.
AB  - OBJECTIVES: To examine individual and regional factors associated with the use of
      intensive medical procedures in the last 6 months of life. DESIGN: Retrospective
      cohort study. SETTING: The Health and Retirement Study (HRS), a longitudinal
      nationally representative cohort of older adults. PARTICIPANTS: HRS decedents
      aged 66 and older (N = 3,069). MEASUREMENTS: Multivariable logistic regression
      was used to evaluate associations between individual and regional factors and
      receipt of five intensive procedures: intubation and mechanical ventilation,
      tracheostomy, gastrostomy tube insertion, enteral and parenteral nutrition, or
      cardiopulmonary resuscitation in the last 6 months of life. RESULTS:
      Approximately 18% of subjects (n = 546) underwent at least one intensive
      procedure in the last 6 months of life. Characteristics significantly associated
      with lower odds of an intensive procedure included aged 85-94 (vs 65-74, adjusted
      odds ratio (AOR) = 0.67, 95% confidence interval (CI) = 0.51-0.90), Alzheimer's
      disease (AOR = 0.71, 95% CI = 0.54-0.94), cancer (AOR = 0.60, 95% CI = 0.43
      0.85), nursing home residence (AOR = 0.70, 95% CI = 0.50-0.97), and having an
      advance directive (AOR = 0.71, 95% CI = 0.57-0.89). In contrast, living in a
      region with higher hospital care intensity (AOR = 2.16, 95% CI = 1.48-3.13) and
      black race (AOR = 2.02, 95% CI = 1.52-2.69) each doubled one's odds of undergoing
      an intensive procedure. CONCLUSION: Individual characteristics and regional
      practice patterns are important determinants of intensive procedure use in the
      last 6 months of life. The effect of nonclinical factors highlights the need to
      better align treatments with individual preferences.

PMID- 25376085
TI  - Anti-angiogenic effect of tanshinone IIA involves inhibition of the VEGF/VEGFR2
      pathway in vascular endothelial cells.
AB  - Tanshinone IIA (TSA) is one of the major lipophilic components of Salvia
      miltiorrhiza Bunge reported to exhibit an antitumor effect. The exact
      intracellular signaling mechanisms involved remain elusive and were therefore the
      subject of this study. The process of angiogenesis is related to tumor
      progression, invasion and metastasis and is generally perceived as an indicator
      of tumor prognosis. Among the most critical factors that induce angiogenesis, the
      vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and
      CD146 (melanoma adhesion molecule) play key roles in this process. This study
      aimed to demonstrate that TSA has potent anti-angiogenic activity in vitro and ex
      vivo. Additionally, we evaluated the role of TSA in the VEGF/VEGFR2 pathway.
      Through a series of in vitro experiments, we found that TSA has a negative effect
      on cell proliferation, migration and tube formation of human umbilical vascular
      endothelial cells. We further showed that TSA can inhibit angiogenesis using
      chorioallantoic membrane (CAM) and rat aortic ring assays. Furthermore, western
      blotting demonstrated that TSA effectively suppressed the expression of VEGR2 and
      CD146. These results suggest that TSA inhibits angiogenesis by downregulation of
      the VEGF/VEGFR2 pathway.

PMID- 25376087
TI  - Editorial on Contributions to nephrology, Vol. 181, by prof. Nan Chen, entitled:
      New insights into glomerulonephritis (pathogenesis and treatment).

PMID- 25376086
TI  - Ara h 2 and Ara h 6 sensitization predicts peanut allergy in Mediterranean
      pediatric patients.
AB  - BACKGROUND: Peanut allergy (PA) management was improved by the introduction of
      molecular allergology, but guidelines for Mediterranean patients are lacking. We
      aimed at evaluating peanut component-resolved diagnosis as a diagnostic and
      prognostic tool in children from Southern France. METHODS: In 181 pediatric
      patients, PA diagnosis was founded on medical history, skin prick testing, serum
      specific IgE to Arachis hypogea extract and components, Pru p 4, and plant
      carbohydrates, and oral food challenge. Allergen microarray was also performed in
      68 of these patients. RESULTS: In peanut-allergic children (n = 117), IgE to Ara
      h 6 were most prevalent (64%), followed by Ara h 2 (63%), Ara h 1 (60%), and Ara
      h 9 (52%). Ara h 6 was the best predictor of PA. The second best predictor was
      the ratio of Ara h 2 IgE to peanut IgE (cutoff 0.113). Persistent childhood PA
      was associated with complex molecular profiles. Comparison of singleplex and
      microarray results showed poor concordance for Ara h 2 and Ara h 9. CONCLUSION:
      Ara h 6 and Ara h 2 are the best predictors of PA at diagnosis in Mediterranean
      pediatric patients. Ara h 1, Ara h 8, and molecular complexity are associated
      with PA persistence.

PMID- 25376088
TI  - SPAK dependent regulation of peptide transporters PEPT1 and PEPT2.
AB  - BACKGROUND/AIMS: SPAK (STE20-related proline/alanine-rich kinase) is a powerful
      regulator of renal tubular ion transport and blood pressure. Moreover, SPAK
      contributes to the regulation of cell volume. Little is known, however, about a
      role of SPAK in the regulation or organic solutes. The present study thus
      addressed the influence of SPAK on the peptide transporters PEPT1 and PEPT2.
      METHODS: To this end, cRNA encoding PEPT1 or PEPT2 were injected into Xenopus
      laevis oocytes without or with additional injection of cRNA encoding wild-type,
      SPAK, WNK1 insensitive inactive (T233A)SPAK, constitutively active (T233E)SPAK,
      and catalytically inactive (D212A)SPAK. Electrogenic peptide (glycine-glycine)
      transport was determined by dual electrode voltage clamp and PEPT2 protein
      abundance in the cell membrane by chemiluminescence. Intestinal electrogenic
      peptide transport was estimated from peptide induced current in Ussing chamber
      experiments of jejunal segments isolated from gene targeted mice expressing SPAK
      resistant to WNK-dependent activation (spak(tg/tg)) and respective wild-type mice
      (spak(+/+)). RESULTS: In PEPT1 and in PEPT2 expressing oocytes, but not in
      oocytes injected with water, the dipeptide gly-gly (2 mM) generated an inward
      current, which was significantly decreased following coexpression of SPAK. The
      effect of SPAK on PEPT1 was mimicked by (T233E)SPAK, but not by (D212A)SPAK or
      (T233A)SPAK. SPAK decreased maximal peptide induced current of PEPT1. Moreover,
      SPAK decreased carrier protein abundance in the cell membrane of PEPT2 expressing
      oocytes. In intestinal segments gly-gly generated a current, which was
      significantly higher in spak(tg/tg) than in spak(+/+) mice. CONCLUSION: SPAK is a
      powerful regulator of peptide transporters PEPT1 and PEPT2.

PMID- 25376090
TI  - Fluorometric assay of integrin activity with a small-molecular probe that senses
      the binding site microenvironment.
AB  - We have developed a small-molecular probe, consisting of cyclic RGD pentapeptides
      bearing a nitrobenzoxadiazole fluorophore at the 4'-residue, which detects
      integrin alphaVbeta3 activity in terms of fluorescence intensity decrease due to
      quenching of the fluorophore by interaction with tyrosine-122 at the binding site
      of the protein. This probe appears to be suitable for a practical, high
      throughput fluorescence assay to screen small-molecular modulators of integrin
      activity. 

PMID- 25376089
TI  - Identification of 19 phthalic acid esters in dairy products by gas chromatography
      with mass spectrometry.
AB  - A detection method for 19 kinds of phthalic acid ester compounds analyzed by n
      hexane/ether/acetonitrile 1:7:8 v/v/v mixed solvent extraction, quick, easy,
      cheap, effective, rugged, and safe purification and internal standard method of
      quantitative gas chromatography with mass spectrometry was established. This
      method can effectively remove interfering materials, such as lipids, fatty acids,
      and pigments, from dairy products. The 19 kinds of phthalic acid ester compounds
      were within a 0.025-0.2 mg/kg range, the recovery rate was 65.2-125.7%, relative
      standard deviation was 7.9-15.4% (n = 6), and the limit of detection was 0.005
      0.02 mg/kg. Concentrations of the 19 kinds of phthalic acid ester compounds
      ranged between 0.01 and 0.12 mg/kg in ten dairy materials and 20 dairy products.
      The established method is simple, rapid, accurate, and highly sensitive.

PMID- 25376091
TI  - Endoscopic ultrasonography-guided pancreatic cyst ablation (with video).
AB  - Pancreatic cystic lesions are being diagnosed with increasing frequency owing to
      the widespread use of cross-sectional imaging. Although most pancreatic cysts are
      detected incidentally, they represent a wide spectrum of histopathology, and
      neoplastic cysts appear to be more prevalent than previously estimated. Some
      histologic types have malignant potential. Considering the perioperative
      morbidity associated with surgical resection, deciding whether to operate or
      observe an indeterminate pancreatic cyst is challenging, and there is a strong
      clinical need to develop a minimally invasive approach. EUS-guided pancreatic
      cyst ablation has been investigated in several clinical trials, and may represent
      a viable alternative to surgical resection. 

PMID- 25376093
TI  - Association between single-nucleotide polymorphisms and early spontaneous
      hepatitis B virus e antigen seroconversion in children.
AB  - BACKGROUND: The disease progression following hepatitis B virus (HBV) infection
      is associated with single-nucleotide polymorphisms (SNPs). However, the role of
      SNPs in chronic HBV infection in children remains unclear. Here, we investigate
      the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg)
      seroconversion in children with chronic hepatitis B infection. METHODS: This was
      a retrospective cohort study. We genotyped seven SNPs in the following genes,
      interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1
      (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and
      IL28B (rs8099917), in patients with chronic HBV infection using PCR and
      sequencing. These variants were analyzed for an association with early HBeAg
      seroconversion in children. RESULTS: Of 225 Japanese patients with chronic
      hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6
      years; range 0-44 years), 52 achieved spontaneous HBeAg seroconversion at the age
      of 10 years or younger (G1: early seroconversion group), and 57 did not achieve
      spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no
      seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p
      value (P = 0.070), but not significant, to have early HBeAg seroconversion in the
      dominant model and in the allele model (P = 0.073) using the chi-square test. The
      association study found a low p-value, but not significant, to have early HBeAg
      seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P =
      0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic
      regression model. CONCLUSION: Although the HLA-DPA1 SNP did not show a
      statistically significant association with early HBeAg seroconversion in this
      study, the HLA-DPA1 SNP might increase the likelihood of achieving early
      spontaneous HBeAg seroconversion in children.

PMID- 25376094
TI  - Univalent Gallium Complexes of Simple and ansa-Arene Ligands: Effects on the
      Polymerization of Isobutylene.
AB  - Using [Ga(C6 H5 F)2 ]+ [Al(ORF )4 ]- (1) (RF =C(CF3 )3 ) as starting material, we
      isolated bis- and tris-eta6 -coordinated gallium(I) arene complex salts of p
      xylene (1,4-Me2 C6 H4 ), hexamethylbenzene (C6 Me6 ), diphenylethane (PhC2 H4
      Ph), and m-terphenyl (1,3-Ph2 C6 H4 ): [Ga(1,4-Me2 C6 H4 )2.5 ]+ (2+ ), [Ga(C6
      Me6 )2 ]+ (3+ ), [Ga(PhC2 H4 Ph)]+ (4+ ) and [(C6 H5 F)Ga(MU-1,3-Ph2 C6 H4 )2
      Ga(C6 H5 F)]2+ (52+ ). 4+ is the first structurally characterized ansa-like bent
      sandwich chelate of univalent gallium and 52+ the first binuclear gallium(I)
      complex without a Ga?Ga bond. Beyond confirming the structural findings by
      multinuclear NMR spectroscopic investigations and density functional calculations
      (RI-BP86/SV(P) level), [Ga(PhC2 H4 Ph)]+ [Al(ORF )4 ]- (4) and [(C6 H5 F)Ga(MU
      1,3-Ph2 C6 H4 )2 Ga(C6 H5 F)]2+ {[Al(ORF )4 ] - }2 (5), featuring ansa-arene
      ligands, were tested as catalysts for the synthesis of highly reactive
      polyisobutylene (HR-PIB). In comparison to the recently published 1 and the
      [Ga(1,3,5-Me3 C6 H3 )2 ]+ [Al(ORF )4 ]- salt (6) (1,3,5-Me3 C6 H3 =mesitylene), 4
      and 5 gave slightly reduced reactivities. This allowed for favorably increased
      polymerization temperatures of up to +15  degrees C, while yielding HR-PIB with
      high contents of terminal olefinic double bonds (alpha-contents=84-93 %), low
      molecular weights (Mn =1000-3000 g mol-1 ) and good monomer conversions (up to 83
      % in two hours). While the chelate complexes delivered more favorable results
      than 1 and 6, the reaction kinetics resembled and thus concurred with the
      recently proposed coordinative polymerization mechanism.

PMID- 25376095
TI  - Whole genome sequencing of Turkish genomes reveals functional private alleles and
      impact of genetic interactions with Europe, Asia and Africa.
AB  - BACKGROUND: Turkey is a crossroads of major population movements throughout
      history and has been a hotspot of cultural interactions. Several studies have
      investigated the complex population history of Turkey through a limited set of
      genetic markers. However, to date, there have been no studies to assess the
      genetic variation at the whole genome level using whole genome sequencing. Here,
      we present whole genome sequences of 16 Turkish individuals resequenced at high
      coverage (32*-48*). RESULTS: We show that the genetic variation of the
      contemporary Turkish population clusters with South European populations, as
      expected, but also shows signatures of relatively recent contribution from
      ancestral East Asian populations. In addition, we document a significant
      enrichment of non-synonymous private alleles, consistent with recent observations
      in European populations. A number of variants associated with skin color and
      total cholesterol levels show frequency differentiation between the Turkish
      populations and European populations. Furthermore, we have analyzed the 17q21.31
      inversion polymorphism region (MAPT locus) and found increased allele frequency
      of 31.25% for H1/H2 inversion polymorphism when compared to European populations
      that show about 25% of allele frequency. CONCLUSION: This study provides the
      first map of common genetic variation from 16 western Asian individuals and thus
      helps fill an important geographical gap in analyzing natural human variation and
      human migration. Our data will help develop population-specific experimental
      designs for studies investigating disease associations and demographic history in
      Turkey.

PMID- 25376096
TI  - Internal quality control for cervical cytopathology: comparison of potential
      false-negatives detected at rapid prescreening and at 100% rapid review.
AB  - OBJECTIVE: To evaluate the performance of rapid prescreening (RPS) and 100% rapid
      review (RR-100%) as internal quality control (IQC) methods assessed by outcome at
      colposcopy, histopathology and repeat cytopathology for cases with false-negative
      results on cervical cytopathology at routine screening (RS). STUDY DESIGN: Out of
      12,208 cytology smears analyzed, 900 were abnormal. Of these, 656 were identified
      at RS, and 244 were false-negative, with 90.2% identified at RPS and 57.4% at RR
      100%. Of the 900 abnormal cases, 436 were submitted for additional testing.
      RESULTS: Of the 244 women with cytopathological abnormalities identified only by
      the IQC methods, 114 had supplementary examinations: 35 were submitted for
      colposcopy, 22 for biopsy and 99 for repeat cytopathology. The sensitivity of RPS
      for the detection of abnormalities identified on colposcopy, histopathology and
      repeat cytopathology was 87.5% (95% CI 67.6-97.3), 82.4% (95% CI 56.6-96.2) and
      95.7% (95% CI 85.2-99.5), respectively. The sensitivity of RR-100% was 54.2% (95%
      CI 32.8-74.4), 52.9% (95% CI 27.8-77.0) and 47.8% (95% CI 32.9-63.1),
      respectively. RPS was more sensitive than RR-100% when compared to the findings
      on colposcopy (p = 0.011) and repeat cytopathology (p = 0.000). When compared to
      colposcopy, histopathology and repeat cytopathology, the sensitivity of RS was
      83.2% (95% CI 76.1-88.9), 85.7% (95% CI 78.1-91.5) and 73.3% (95% CI 66.0-79.7),
      respectively. CONCLUSION: RPS performed better than RR-100% when compared to the
      results of colposcopy and repeat cytopathology.

PMID- 25376098
TI  - Assessment of quality control approaches for metagenomic data analysis.
AB  - Currently there is an explosive increase of the next-generation sequencing (NGS)
      projects and related datasets, which have to be processed by Quality Control (QC)
      procedures before they could be utilized for omics analysis. QC procedure usually
      includes identification and filtration of sequencing artifacts such as low
      quality reads and contaminating reads, which would significantly affect and
      sometimes mislead downstream analysis. Quality control of NGS data for microbial
      communities is especially challenging. In this work, we have evaluated and
      compared the performance and effects of various QC pipelines on different types
      of metagenomic NGS data and from different angles, based on which general
      principles of using QC pipelines were proposed. Results based on both simulated
      and real metagenomic datasets have shown that: firstly, QC-Chain is superior in
      its ability for contamination identification for metagenomic NGS datasets with
      different complexities with high sensitivity and specificity. Secondly, the high
      performance computing engine enabled QC-Chain to achieve a significant reduction
      in processing time compared to other pipelines based on serial computing.
      Thirdly, QC-Chain could outperform other tools in benefiting downstream
      metagenomic data analysis. 

PMID- 25376099
TI  - The contribution of imaging in the diagnosis and treatment of axial
      spondyloarthritis.
AB  - BACKGROUND: The concept of axial Spondyloarthritis (axSpA) includes patients with
      non-radiographic axSpA and ankylosing spondylitis (AS). Inflammatory and
      chronic/structural changes of the sacroiliac joints and the spine are
      pathognomonic in patients who are diagnosed with axSpA. MATERIALS AND METHODS: In
      the last years, the evaluation of the natural course of axSpA has been in the
      focus of research, especially with respect to the relationship between
      inflammation or postinflammatory changes [detected by magnetic resonance imaging
      (MRI)] and bone formation (detected by conventional radiographs). RESULTS: Based
      on the analysis of spinal MRI data, development of new syndesmophytes is directly
      associated with the parallel occurrence of inflammatory and postinflammatory
      (fatty) changes in the edges of the vertebral bodies. In contrast, vertebral
      edges that show only inflammation but no transformation into fatty lesions show a
      decreased relative risk for development of new bone formation over time. An
      inhibitory effect on radiographic progression had not been demonstrated during
      the first 2 years of continuous anti-TNFa treatment, however, very recently first
      studies reported a decreased rate of radiographic progression when patients were
      continuously treated with TNFa-blockers for a time period of >=4 years.
      CONCLUSIONS: These data are crucial in the understanding of the long-term
      clinical course of patients with axSpAin daily practice. According to these
      results, it becomes obvious that anti-inflammatory treatment, especially by using
      tumor-necrosis-factor alpha (TNFa)-blockers, has the best effect on the
      radiographic outcomes when it is started in anearly disease stage, where only
      inflammation is driving the disease activity and where structural,
      postinflammatory changes have not yet occurred.

PMID- 25376102
TI  - Frustrated Lewis pair activation of an N-sulfinylamine: a source of sulfur
      monoxide.
AB  - Inter- and intramolecular P/B frustrated Lewis pairs are shown to react with an N
      sulfinylamine to form PNSOB linakages. These species can be regarded as
      phosphinimine-borane-stabilized sulfur monoxide complexes, and indeed these
      species act as sources of SO, effecting the oxidation of PPh3 and delivering SO
      to [RhCl(PPh3)3] and an N-heterocyclic carbene.

PMID- 25376101
TI  - Diagnostic imaging in pediatric polytrauma management.
AB  - Trauma is the cause of over 45% of deaths in children aged 1 to 14 years. Since
      multiple injuries are common among children, the emergency physician has to
      assess all the organs of a high-energy injured child, independent of mechanism of
      the trauma. Even if the principles of polytrauma management are identical both in
      children and in adults, the optimal pediatric patient care requires a specific
      understanding of some important anatomical, physiological, and psychological
      differences that play a significant role in the assessment and management of a
      pediatric patient. Emergency Radiology already plays a crucial role in the
      diagnostic process of a polytraumatized child according to the primary survey,
      through the use of multiple imaging modalities. Radiological and Ultrasound
      examinations play a basic role in the hemodynamically unstable patients. In the
      hemodynamically stable patients whole-body CT scanning is the most immediate
      radiological procedure that allows the examination of all the body parts of a
      polytraumatized child, reducing the number of minor injuries that might otherwise
      be neglected.

PMID- 25376103
TI  - beta-Ga2O3 nanorod synthesis with a one-step microwave irradiation hydrothermal
      method and its efficient photocatalytic degradation for perfluorooctanoic acid.
AB  - beta-Ga2O3 nanorod was first directly prepared by the microwave irradiation
      hydrothermal way without any subsequent heat treatments, and its
      characterizations were analyzed by X-ray diffraction (XRD), scanning electron
      microscope (SEM), high-resolution transmission electron microscope (HRTEM), UV
      Vis diffuse reflection spectroscopy techniques, and also its photocatalytic
      degradation for perfluorooctanoic acid (PFOA) was investigated. XRD patterns
      revealed that beta-Ga2O3 crystallization increased with the enhancement of
      microwave power and the adding of active carbon (AC). PFOA, as an environmental
      and persistent pollutant, is hard decomposed by hydroxyl radicals (HO.); however,
      it is facilely destroyed by beta-Ga2O3 photocatalytic reaction in an anaerobic
      atmosphere. The important factors such as pH, beta-Ga2O3 dosage and bubbling
      atmosphere were researched, and the degradation and defluorination was 98.8% and
      56.2%, respectively. Reductive atmosphere reveals that photoinduced electron may
      be the major reactant for PFOA. Furthermore, the degradation kinetics for PFOA
      was simulated and constant and half-life was calculated, respectively.

PMID- 25376104
TI  - Comparison of the Cellient(TM) automated cell block system and agar cell block
      method.
AB  - OBJECTIVE: To compare the Cellient(TM) automated cell block system with the agar
      cell block method in terms of quantity and quality of diagnostic material and
      morphological, histochemical and immunocytochemical features. MATERIALS AND
      METHODS: Cell blocks were prepared from 100 effusion samples using the agar
      method and Cellient system, and routinely sectioned and stained for haematoxylin
      and eosin and periodic acid-Schiff with diastase (PASD). A preliminary
      immunocytochemical study was performed on selected cases (27/100 cases). Sections
      were evaluated using a three-point grading system to compare a set of
      morphological parameters. Statistical analysis was performed using Fisher's exact
      test. RESULTS: Parameters assessing cellularity, presence of single cells and
      definition of nuclear membrane, nucleoli, chromatin and cytoplasm showed a
      statistically significant improvement on Cellient cell blocks compared with agar
      cell blocks (P < 0.05). No significant difference was seen for definition of cell
      groups, PASD staining or the intensity or clarity of immunocytochemical staining.
      A discrepant immunocytochemistry (ICC) result was seen in 21% (13/63) of
      immunostains. CONCLUSION: The Cellient technique is comparable with the agar
      method, with statistically significant results achieved for important
      morphological features. It demonstrates potential as an alternative cell block
      preparation method which is relevant for the rapid processing of fine needle
      aspiration samples, malignant effusions and low-cellularity specimens, where
      optimal cell morphology and architecture are essential. Further investigation is
      required to optimize immunocytochemical staining using the Cellient method.

PMID- 25376105
TI  - Facile Construction of Pt-Co/CNx Nanotube Electrocatalysts and Their Application
      to the Oxygen Reduction Reaction.
AB  - A straight forward method for immobilizing Pt-Co alloyed nanoparticles onto
      nitrogen-doped CNx nanotubes is presented. The as-prepared electrocatalysts
      exhibit good performance for oxygen reduction reaction in acidic medium arising
      from the high-dispersion and alloying effect of the Pt-Co nanoparticles and the
      intrinsic catalytic capacity of the CNx nanotubes. 

PMID- 25376097
TI  - Is there new hope for therapeutic matrix metalloproteinase inhibition?
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that form a
      family of 24 members in mammals. Evidence of the pathological roles of MMPs in
      various diseases, combined with their druggability, has made them attractive
      therapeutic targets. Initial drug discovery efforts focused on the roles of MMPs
      in cancer progression, and more than 50 MMP inhibitors have been investigated in
      clinical trials in various cancers. However, all of these trials failed. Reasons
      for failure include the lack of inhibitor specificity and insufficient knowledge
      about the complexity of the disease biology. MMPs are also known to be involved
      in several inflammatory processes, and there are new therapeutic opportunities
      for MMP inhibitors to treat such diseases. In this Review, we discuss the recent
      advances made in understanding the role of MMPs in inflammatory diseases and the
      therapeutic potential of MMP inhibition in those conditions. 

PMID- 25376106
TI  - Total synthesis of 6-deoxypladienolide D and Assessment of Splicing Inhibitory
      Activity in a Mutant SF3B1 cancer cell line.
AB  - A total synthesis of the natural product 6-deoxypladienolide D (1) has been
      achieved. Two noteworthy attributes of the synthesis are (1) a late-stage allylic
      oxidation which proceeds with full chemo-, regio-, and diastereoselectivity and
      (2) the development of a scalable and cost-effective synthetic route to support
      drug discovery efforts. 6-Deoxypladienolide D (1) demonstrates potent growth
      inhibition in a mutant SF3B1 cancer cell line, high binding affinity to the SF3b
      complex, and inhibition of pre-mRNA splicing. 

PMID- 25376107
TI  - Increased numbers of tryptase-positive mast cells in the healthy and sun
      protected skin of tobacco smokers.
AB  - BACKGROUND: Tobacco smoking may cause skin aging through mast cell proteinases.
      OBJECTIVE: To compare the numbers of mast cells showing tryptase and chymase in
      the healthy-looking skin of smokers and non-smokers. METHODS: The study subjects
      consisted of 80 males, 42 of whom were smokers and 38 non-smokers. A skin biopsy
      from the medial arm was processed for immunohistochemical staining of tryptase
      and chymase, as well as chymase inhibitors alpha-1-proteinase inhibitor (alpha-1
      PI) and alpha-1-antichymotrypsin (alpha-1-AC). RESULTS: The number of tryptase(+)
      mast cells was significantly higher in the smoker group (84 +/- 32 cells/mm(2))
      than in the non-smoker group (70 +/- 32 cells/mm(2)) (p = 0.044). Likewise, the
      number of chymase(+) mast cells was higher in the smoker group (89 +/- 20 vs. 80
      +/- 22 cells/mm(2)), though statistical significance was not reached (p = 0.07).
      No significant difference was observed in alpha-1-PI(+) and alpha-1-AC(+) cells.
      CONCLUSION: Especially tryptase, but probably also chymase, may have an influence
      on the skin of smokers, such as wrinkling and aging.

PMID- 25376108
TI  - beta-Amyloid peptides display protective activity against the human Alzheimer's
      disease-associated herpes simplex virus-1.
AB  - Amyloid plaques, the hallmark of Alzheimer's disease (AD), contain fibrillar beta
      amyloid (Abeta) 1-40 and 1-42 peptides. Herpes simplex virus 1 (HSV-1) has been
      implicated as a risk factor for AD and found to co-localize within amyloid
      plaques. Abeta 1-40 and Abeta 1-42 display anti-bacterial, anti-yeast and anti
      viral activities. Here, fibroblast, epithelial and neuronal cell lines were
      exposed to Abeta 1-40 or Abeta 1-42 and challenged with HSV-1. Quantitative
      analysis revealed that Abeta 1-40 and Abeta 1-42 inhibited HSV-1 replication when
      added 2 h prior to or concomitantly with virus challenge, but not when added 2 or
      6 h after virus addition. In contrast, Abeta 1-40 and Abeta 1-42 did not prevent
      replication of the non-enveloped human adenovirus. In comparison, antimicrobial
      peptide LL-37 prevented HSV-1 infection independently of its sequence of
      addition. Our findings showed also that Abeta 1-40 and Abeta 1-42 acted directly
      on HSV-1 in a cell-free system and prevented viral entry into cells. The sequence
      homology between Abeta and a proximal transmembrane region of HSV-1 glycoprotein
      B suggested that Abeta interference with HSV-1 replication could involve its
      insertion into the HSV-1 envelope. Our data suggest that Abeta peptides represent
      a novel class of antimicrobial peptides that protect against neurotropic
      enveloped virus infections such as HSV-1. Overproduction of Abeta peptide to
      protect against latent herpes viruses and eventually against other infections,
      may contribute to amyloid plaque formation, and partially explain why brain
      infections play a pathogenic role in the progression of the sporadic form of AD. 

PMID- 25376109
TI  - Sarcopenic obesity: molecular clues to a better understanding of its
      pathogenesis?
AB  - An age-dependent decline in skeletal muscle mass, strength, and endurance during
      the aging process is a physiological development, but several factors may
      exacerbate this process, leading to the threatening state of sarcopenia, frailty,
      and eventually higher mortality rates. Obesity appears to be such a promoting
      factor and has been linked in several studies to sarcopenia. The reason for this
      causal association remains poorly understood. Notwithstanding the fact that a
      higher body mass might simply lead to diminished physical activity and therefore
      contribute to a decline in skeletal muscle, several molecular mechanisms have
      been hypothesized. There could be an obesity derived intracellular lipotoxicity
      (i.e., elevated intramuscular levels of lipids and their derivatives), which
      induces apoptosis by means of an elevated oxidative stress. Paracrine mechanisms
      and inflammatory cytokines, such as CRP and IL-6 could be confounders of the
      actual underlying pathological mechanism. Due to a cross-talk of the hypothalamo
      pituitary axis with nutritional status, obese subjects are more in a catabolic
      state of metabolism, with a higher susceptibility to muscle wasting under energy
      restriction. Obesity induces insulin resistance in the skeletal muscle, which
      consequently leads to perturbed metabolism, and misrouted signaling in the muscle
      cells. In obesity, muscle progenitor cells could differentiate to an adipocyte
      like phenotype as a result of paracrine signals from (adipo)cytokines leading to
      a reduced muscular renewal capacity. The present review outlines current
      knowledge concerning possible pathways, which might be involved in the molecular
      pathogenesis of sarcopenic obesity. 

PMID- 25376110
TI  - Integration of a postoperative calcitonin measurement into an anatomical staging
      system improves initial risk stratification in medullary thyroid cancer.
AB  - OBJECTIVE: Staging systems applied to medullary thyroid cancer (MTC) rely on
      initial clinical and pathological features and do not consider the response to
      treatment. To determine whether MTC staging can be improved by incorporating the
      first postoperative calcitonin measurement. PATIENTS AND MEASUREMENTS: Eighty
      five patients being monitored for MTC (median follow-up 5 years) were
      retrospectively classified according to both the American Joint Committee on
      Cancer (AJCC) and the proposed combined risk stratification system (low,
      intermediate and high risk), which incorporates the first postoperative
      calcitonin measurement, using the outcomes no evidence of disease (NED),
      biochemical evidence of disease, structurally identifiable disease and death.
      RESULTS: Ninety per cent of AJCC I patients were classified as NED at final
      follow-up. When we added a postoperative calcitonin measurement, 95% low-risk
      patients were classified as NED at final follow-up. AJCC stages I and IV were
      associated, respectively, with no occurrence and a high rate (63%) of
      structurally identifiable disease. Stages II and III yielded similar predictions
      of structurally identifiable disease, 13% and 14%, respectively. When we included
      the postoperative calcitonin level, the patients with structural evidence of
      disease included none from the low-risk group, 10% from the intermediate group
      and 63% from the high-risk group. The proportion of variance explained analysis
      (PVE) was better for the combined risk stratification system (54%) than for the
      AJCC system alone (32%). CONCLUSION: Including the first postoperative calcitonin
      measurement with the anatomical staging system can better predict the clinical
      outcome of patients with MTC and refine the follow-up of these patients.

PMID- 25376111
TI  - A PCR detection method for testing Mycoplasma contamination of veterinary
      vaccines and biological products.
AB  - A rapid test method was developed for detecting mycoplasma contamination in
      veterinary biological products. The method reduces testing time by 2 weeks and
      shows comparable sensitivity to the current agar-based detection model. The
      primary goals for the development of the test were to reduce the testing time,
      incorporate a method that was easily adaptable across the veterinary biologics
      industry and reduce the subjective interpretation of results. We found that
      biological enrichment is necessary to maintain sensitivity of the detection
      method when compared to the standard culture-based test and that periodic
      sampling of enrichment cultures is essential to detect a wide variety of
      mycoplasma species that may be present as contaminants. The PCR detection method
      is comparable to the agar-based model and can reduce the overall testing time by
      up to 14 days.

PMID- 25376112
TI  - Factors influencing the toxicity, detoxification and biotransformation of
      paralytic shellfish toxins.

PMID- 25376113
TI  - Sources, fluxes, and biogeochemical cycling of silver in the oceans.

PMID- 25376114
TI  - DDT, chlordane, toxaphene and PCB residues in Newport Bay and Watershed:
      assessment of hazard to wildlife and human health.

PMID- 25376116
TI  - Postoperative radiotherapy for patients at high risk of recurrence of oral cavity
      squamous cell carcinoma.
AB  - OBJECTIVES: To evaluate the efficacy of postoperative radiotherapy for oral
      cavity squamous cell carcinoma (OCSCC) by comparing outcomes of high-risk
      subgroups. STUDY DESIGN: Retrospective review. METHODS: Outcome study of 139
      patients with OCSCC treated with gross total resection and postoperative
      radiotherapy +/- chemotherapy and at least one high-risk pathologic finding:
      positive margin (52%), close (0.1-5 mm) margin (27%), or extracapsular nodal
      extension (ECE; 45%). RESULTS: Median follow-up was 2.3 years. Local-regional
      control (LRC), freedom from distant metastases, cause-specific survival, and
      overall survival (OS) rates at 5 years were 64%, 85%, 51%, and 36%, respectively.
      Five-year LRC for negative (>5 mm), close (0.1-5 mm), and positive (carcinoma in
      situ or tumor at ink) margins were 73%, 83%, and 63%, respectively (P = not
      significant). Five-year neck control was 100% for node-negative patients, 88% for
      node-positive patients with no ECE, and 86% for node-positive patients with ECE
      (P = not significant). The combination of close/positive margin and ECE resulted
      in worse 5-year LRC (37% vs. 70%, P < 0.001), progression-free survival (26% vs.
      60%, P < 0.001), and OS (13 vs. 43%, P < 0.001) compared with a single high-risk
      indication. CONCLUSIONS: Local-regional control was the predominant mode of
      treatment failure. Outcome in our series was not statistically different based on
      margin status or nodal ECE. This finding is indirect evidence of the efficacy of
      adjuvant radiotherapy in this setting.

PMID- 25376115
TI  - HDAC-inhibitor (S)-8 disrupts HDAC6-PP1 complex prompting A375 melanoma cell
      growth arrest and apoptosis.
AB  - Histone deacetylase inhibitors (HDACi) are agents capable of inducing growth
      arrest and apoptosis in different tumour cell types. Previously, we reported a
      series of novel HDACi obtained by hybridizing SAHA or oxamflatin with 1,4
      benzodiazepines. Some of these hybrids proved effective against haematological
      and solid cancer cells and, above all, compound (S)-8 has emerged for its
      activities in various biological systems. Here, we describe the effectiveness of
      (S)-8 against highly metastatic human A375 melanoma cells by using normal PIG1
      melanocytes as control. (S)-8 prompted: acetylation of histones H3/H4 and alpha
      tubulin; G0 /G1 and G2 /M cell cycle arrest by rising p21 and hypophos-phorylated
      RB levels; apoptosis involving the cleavage of PARP and caspase 9, BAD protein
      augmentation and cytochrome c release; decrease in cell motility, invasiveness
      and pro-angiogenic potential as shown by results of wound-healing assay, down
      regulation of MMP-2 and VEGF-A/VEGF-R2, besides TIMP-1/TIMP-2 up-regulation; and
      also intracellular accumulation of melanin and neutral lipids. The pan-caspase
      inhibitor Z-VAD-fmk, but not the antioxidant N-acetyl-cysteine, contrasted these
      events. Mechanistically, (S)-8 allows the disruption of cytoplasmic HDAC6-protein
      phosphatase 1 (PP1) complex in A375 cells thus releasing the active PP1 that
      dephosphorylates AKT and blocks its downstream pro-survival signalling. This view
      is consistent with results obtained by: inhibiting PP1 with Calyculin A; using
      PPP1R2-transfected cells with impaired PP1 activity; monitoring drug-induced
      HDAC6-PP1 complex re-shuffling; and, abrogating HDAC6 expression with specific
      siRNA. Altogether, (S)-8 proved very effective against melanoma A375 cells, but
      not normal melanocytes, and safe to normal mice thus offering attractive clinical
      prospects for treating this aggressive malignancy. 

PMID- 25376117
TI  - Preface.

PMID- 25376118
TI  - Consensual intercourse resulting in an extensive rectovaginal tear: an extremely
      rare occurrence.
AB  - INTRODUCTION: Rectovaginal tears are usually associated with the insertion of
      foreign bodies, accidental trauma, and nonconsensual intercourse. AIM: The aim of
      this study was to describe an extremely rare case of extensive rectovaginal tear
      as a result of consensual vaginal and anal intercourse. METHODS: A case is
      presented along with review of the literature. RESULTS: A 20-year-old woman
      presented with acute perineal pain and minor vaginal bleeding following
      consensual vaginal and anal intercourse. No insertion of sex toy or any other
      object was reported. Vaginal and rectal examination revealed a ruptured posterior
      vaginal wall with wide communication with the rectum, without involvement of the
      anal sphincters. Surgical treatment with primary repair of the tear and diverting
      colostomy was performed. CONCLUSIONS: Although consensual intercourse is usually
      associated with minor genital trauma, rare but potentially serious injuries can
      occur. Clinicians should be aware of the possibility of such injuries because
      failure to identify them can lead to delayed treatment and poor outcome.

PMID- 25376120
TI  - Posterior staphyloma is related to optic disc morphology and the location of
      visual field defect in normal tension glaucoma patients with myopia.
AB  - PURPOSE: To determine the morphologic features of the optic disc and the location
      of visual field (VF) defect in relation to posterior staphyloma in normal tension
      glaucoma (NTG) eyes with myopia. METHODS: One hundred and thirty-four NTG
      patients with myopia were enrolled. B-scan ultrasonography was performed in
      enrolled patients. Disc tilt ratio, disc torsion, and area of peripapillary
      atrophy were measured from disc photographs. Patients were classified according
      to the presence of posterior staphyloma and its location: staphyloma involving
      the optic disc, staphyloma involving either the supero-temporal side of the optic
      disc or the infero-temporal side of the optic disc. The relationship between the
      location of the posterior staphyloma and that of the VF defect was analyzed.
      RESULTS: Among 134 eyes, 74 eyes (55.2%) had posterior staphyloma on B-scan
      ultrasonography. Mean torsion degree was significantly greater in eyes with
      staphyloma involving the temporal side of the optic disc (19.78+/-18.00 degrees )
      compared with eyes with staphyloma involving the optic disc (4.65+/-4.92 degrees
      , P=0.001). The frequency of the location of VF damage differed significantly
      between eyes with staphyloma involving the supero-temporal side and those
      involving the infero-temporal side of the optic disc (P=0.008), which was not
      significant in eyes with staphyloma involving the optic disc (P=0.813).
      CONCLUSIONS: Optic disc torsion was a prominent finding in myopic NTG eyes when
      posterior staphyloma was located temporal to the optic disc. The location of
      posterior staphyloma was related to the direction of disc torsion and the
      location of VF defect.

PMID- 25376119
TI  - Neuropathic ocular pain: an important yet underevaluated feature of dry eye.
AB  - Dry eye has gained recognition as a public health problem given its prevalence,
      morbidity, and cost implications. Dry eye can have a variety of symptoms
      including blurred vision, irritation, and ocular pain. Within dry eye-associated
      ocular pain, some patients report transient pain whereas others complain of
      chronic pain. In this review, we will summarize the evidence that chronicity is
      more likely to occur in patients with dysfunction in their ocular sensory
      apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction
      includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and
      corneal nerve morphologic and functional abnormalities. Both peripheral and
      central sensitizations likely play a role in generating the noted clinical
      characteristics. We will further discuss how evaluating for neuropathic ocular
      pain may affect the treatment of dry eye-associated chronic pain. 

PMID- 25376121
TI  - Drusen and RPE atrophy automated quantification by optical coherence tomography
      in an elderly population.
AB  - PURPOSE: Correlate OCT-derived measures of drusen and retinal pigment epithelium
      (RPE) atrophy areas (RAs) with demographic features in an elderly population.
      PATIENTS AND METHODS: Subjects aged 50 years and older underwent Cirrus OCT
      scanning. Drusen area and volume were obtained from the macula within a central
      circle (CC) of 3 mm and a surrounding perifoveal ring (PR) of 3-5 mm, using the
      RPE analysis software (6.0). RA measurements were generated for the 6 * 6 mm(2)
      retinal area. Gender, age, smoking status, and systolic blood pressure (SBP) were
      considered. RESULTS: A total of 434 eyes were included. RA was larger in women
      (0.63+/-0.16 vs 0.26+/-0.08 mm(2), P=0.05) and with increasing age. The PR drusen
      area increased with increasing age (P<0.001), whereas the CC drusen area remained
      stable after the age of 70 years (0.25+/-0.06 mm(2) for ages 70-79 years and
      0.25+/-0.07 mm(2) for ages >80 years). Drusen volume in the CC was smaller after
      the age of 80 years (0.009+/-0.003 mm(3)) compared with the 70- to 79-year-old
      group (0.02+/-0.008 mm(3)). Drusen measurements were similar between smokers and
      nonsmokers, but the PR drusen area (0.29 mm(2), P=0.05) and volume (0.40 mm(3),
      P=0.005) were correlated with years smoked. RA (0.24 mm(2), P=0.10), PR drusen
      area (0.29 mm(2), P=0.05), and volume (0.40 mm(3), P=0.005) were found to be
      directly associated with SBP. There was a high correlation between the eyes of
      the same subject. CONCLUSION: OCT-based automated algorithms can be used to
      analyze and describe drusen and geographic atrophy burden in such population
      based studies of elderly patients.

PMID- 25376122
TI  - MicroRNA profiling of low-grade and transformed nodal marginal zone lymphoma
      reveals a similar signature pattern distinct from diffuse large B cell lymphoma.
AB  - BACKGROUND/AIMS: As critical post-transcriptional regulators of gene expression,
      microRNAs are involved in several cellular processes of vital impact including
      cell growth and apoptosis. Many hematologic malignancies exhibit distinct
      microRNA signatures. MicroRNA implication in the pathogenesis of nodal marginal
      zone lymphoma (NMZL), however, remains widely elusive. METHODS: Comprehensive
      morphologic, immunophenotypic and cytogenetic studies were carried out on a
      cohort of NMZL (n = 30) incorporating indolent as well as transformed MZL. In
      addition, microRNA signatures were generated, employing a quantitative real-time
      polymerase chain reaction approach. These were then compared to signatures from
      cases of diffuse large B cell lymphoma (DLBCL) alongside reactive lymph node
      controls. RESULTS: While microRNA signatures of low-grade and transformed NMZL
      did not differ significantly, several microRNAs were differentially expressed
      between transformed NMZL and DLBCL, hinting at molecularly distinct mechanisms of
      lymphomagenesis and indicating the biological disparity of transformed NMZL from
      DLBCL. CONCLUSION: In the light of the unresolved issue regarding the
      classification of marginal zone-derived transformed B-cell neoplasms, microRNAs
      may be a valuable aid in discriminating NMZL from DLBCL.

PMID- 25376123
TI  - Good is not Good Enough: The Benchmark Stroke Door-to-Needle Time Should be 30
      Minutes.

PMID- 25376126
TI  - "It is an Issue of not Knowing Where to Go": Service Providers' Perspectives on
      Challenges in Accessing Social Support and Services by Immigrant Mothers of
      Children with Disabilities.
AB  - In Canada little is known about the challenges immigrant mothers of children with
      disabilities encounter in accessing formal and informal social support. This
      paper presents the perspectives of service providers on the mothers' challenges.
      Data was collected from 27 service providers in Toronto, Canada in 2012 through
      in-depth interviews. The interview guide was informed by published literature on
      families of children with special needs. Level one analyses entailed descriptive
      analyses; and level two consisted of applying House's 4 domains of social support
      to organize the themes. Following House's domains, challenges to (1) Structural
      support, (2) Instrumental support, (3) Emotional support, and (4) Perception of
      support were identified. Among providers who work with families of children with
      disabilities there is recognition of the mothers' particular challenges in light
      of their immigration status. Language and communication are significant barriers
      for immigrant mothers in accessing social support. 

PMID- 25376125
TI  - Multimodal neuroimaging evidence of alterations in cortical structure and
      function in HIV-infected older adults.
AB  - Combination antiretroviral therapy transformed human immunodeficiency virus (HIV)
      infection from a terminal illness to a manageable condition, but these patients
      remain at a significantly elevated risk of developing cognitive impairments and
      the mechanisms are not understood. Some previous neuroimaging studies have found
      hyperactivation in frontoparietal networks of HIV-infected patients, whereas
      others reported aberrations restricted to sensory cortices. In this study, we
      utilize high-resolution structural and neurophysiological imaging to determine
      whether alterations in brain structure, function, or both contribute to HIV
      related cognitive impairments. HIV-infected adults and individually matched
      controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a
      mechanoreception task during magnetoencephalography (MEG). MEG data were examined
      using advanced beamforming methods, and sMRI data were analyzed using the latest
      voxel-based morphometry methods with DARTEL. We found significantly reduced theta
      responses in the postcentral gyrus and increased alpha activity in the prefrontal
      cortices of HIV-infected patients compared with controls. Patients also had
      reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and
      other regions. Importantly, reduced gray matter volume in the left postcentral
      gyrus was spatially coincident with abnormal MEG responses in HIV-infected
      patients. Finally, left prefrontal and postcentral gyrus activity was correlated
      with neuropsychological performance and, when used in conjunction, these two MEG
      findings had a sensitivity and specificity of over 87.5% for HIV-associated
      cognitive impairment. This study is the first to demonstrate abnormally increased
      activity in association cortices with simultaneously decreased activity in
      sensory areas. These MEG findings had excellent sensitivity and specificity for
      HIV-associated cognitive impairment, and may hold promise as a potential disease
      marker.

PMID- 25376124
TI  - Influence of food patterns on endothelial biomarkers: a systematic review.
AB  - The purpose of this study was to conduct a systematic review on the association
      of food patterns (FPs) and endothelial biomarkers. An electronic literature
      search from 1990 to 2012 was conducted and reference lists and experts were
      consulted. Studies without dietary intervention and without language restrictions
      were considered. Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines were employed. Methodological quality was assessed by
      Strengthening the Reporting of Observational Studies in Epidemiology guidelines.
      A total of 546 references were identified, of which 8 were finally included.
      Several FPs were identified. Healthy FPs (abundant in fruits and vegetables) had
      a beneficial impact on endothelial function as estimated by circulating levels of
      biomarkers such as C-reactive protein, soluble intercellular adhesion molecule 1,
      soluble vascular adhesion molecule 1, and E-selectin molecules. Westernized
      patterns (higher intakes of processed meats, sweets, fried foods, and refined
      grains) were positively associated with inflammation molecules and atherogenic
      promoters. The study of FPs in relation to endothelial function contributes to
      the development of dietary recommendations for improved cardiovascular health and
      therefore a better lifestyle. 

PMID- 25376127
TI  - More than Just Not Enough: Experiences of Food Insecurity for Latino Immigrants.
AB  - Undocumented Latino immigrants often struggle to provide food for their families.
      In an attempt to inform efforts to create effective programs and policies
      promoting food security, this study explored the experience of food insecurity
      for low-income, undocumented Latino immigrants. In-depth qualitative interviews
      were conducted with 24 undocumented Latino immigrants. Modified grounded theory
      was used to analyze the interview data. The experience of food insecurity was
      similar to other groups' experiences, as it entailed inadequate amount and
      quality of food. However, immigration and documentation status presented unique
      vulnerabilities for food insecurity related to unfamiliar food environments,
      remittances and separation, employment, and community and government resources.
      Cultural and structural factors that may shape the experience of and response to
      food insecurity are discussed along with implications for policy and programming.

PMID- 25376128
TI  - Pre- and Post-displacement Stressors and Body Weight Development in Iraqi
      Refugees in Michigan.
AB  - Refugees have typically experienced stress and trauma before entering the US.
      Stressors and mental health disorders may contribute to obesity. The aim of this
      study was to investigate changes in the body mass index (BMI) in Iraqi refugees
      settled in Michigan in relationship to pre- and post-migration stressors and
      mental health. Anthropometric and demographic data were collected from 290 Iraqi
      refugees immediately after they arrived in Michigan and one year after
      settlement. Significant increases were observed in BMI (+0.46 +/- 0.09 kg/m(2), p
      < 0.0001) and the percentage of refugees suffering from hypertension (from 9.6 to
      13.1%, p < 0.05). Significant increases in stress, depression and acculturation,
      as well as decreases in post-migration trauma and social support, were also
      observed. Linear regression analyses failed to link stressors, well-being, and
      mental health to changes in BMI. It is likely that acculturation to a new
      lifestyle, including dietary patterns and physical activity levels, may have
      contributed to these changes.

PMID- 25376129
TI  - Greek Immigrants in Australia: Implications for Culturally Sensitive Practice.
AB  - This exploratory research examined adjustment challenges, resiliencies,
      attitudes, emotional health, economic stability, criminal involvement,
      victimization and service experiences, and some cultural propensities of Greek
      Immigrants (GIs) in Australia using a convenient multi-generational sample (n =
      123; response rate = .5). Data were collected via surveys, telephone, and
      personal-interviews in four major Australian cities. Among other things, the
      study revealed that Greek identity and cultural customs are often significant to
      first generation GIs. Adjustment challenges upon entry include primarily
      language, housing, and transportation difficulties, nostalgia for relatives and
      the motherland, unfamiliarity with socio-cultural systems, unemployment, money
      challenges, and lack of friendships. Christian faith, the extended family, family
      values and traditions, cultural pride for ancient Greek achievements, and a hard
      'work ethic' are notable resiliencies that support GIs in their struggles and
      solidify their pursuit for happiness and success. Financial concerns, aging, and
      nostalgia for relatives and the motherland were the primary causes of socio
      emotional instability. Attitudinal differences in the respondents based on age,
      gender, and socio-economic status, cross-cultural comparisons, and
      recommendations for culturally-sensitive practice with GIs are analyzed and
      methodological limitations illuminated. Future research needs in the field are
      also highlighted.

PMID- 25376130
TI  - Are Recent Immigrants Larger than Earlier Ones at Their Arrival? Cohort Variation
      in Initial BMI among US Immigrants, 1989-2011.
AB  - Studies have reported that newly-arrived immigrants to the US often have better
      health outcomes, including lower body mass index (BMI) than established ones.
      This study tests the hypothesis about variation in initial BMI among immigrants
      who have come to the US during different time periods. Using 1989-2011 data from
      NHIS, we found that recent immigrants in general were larger at their time of
      arrival than the earlier ones. However, we also observed variations in initial
      BMI across racial and ethnic origin groups. For example, we found the trends for
      Hispanic and Asian immigrants to have increased during the study period. The
      average initial BMI for recent Hispanic immigrant cohorts surpassed the upper
      limit for normal weight. While earlier cohorts of Asian immigrants had much lower
      initial BMI than other immigrant groups, the estimated annual increase among
      Asians was the most rapid. Our findings support the observation about the rising
      body weight and obesity rates worldwide. The policy implications of our findings
      were also discussed. 

PMID- 25376132
TI  - Xenotransplantation of human adipose derived mesenchymal stem cells in a rodent
      model of Huntington's disease: motor and non-motor outcomes.
AB  - Human mesenchymal stem cells (hMSCs) have been presented as alternative sources
      of cells to be transplanted into the brain in neurodegenerative disorders. In
      this regard, the efficacy of hMSCs transplants in reducing motor and non-motor
      deficits in a quinolinic acid (QA) rat model of Huntington's disease (HD) was
      tested in the present study. After unilateral lesions in striatum by QA, the
      isolated and purified hMSCs from liposuction of healthy male donors were
      transplanted into the damaged striatum of the rats. The cells were stably
      transfected with a vector containing TurboGFP and JRed to make it possible to
      trace them after transplantation. Animals were tested by motor and non-motor
      function tests at different times after the cell transplantation. The hMSCs
      survived 7 weeks in the brains. An improvement was observed in behavioral tests
      such as apomophine-induced rotation, hanging wire, and rotarod for the hMSC
      treated rats. Anxiety like behaviors were decreased in hMSCs-treated animals when
      they were examined using open field, elevated plus maze, light and dark box, and
      novelty suppressed feeding tests. Compared to QA, the hMSCs treatment decreased
      motor activities. These results confirmed the potential efficacy of hMSCs in
      treatment of behavioral defects in HD. Generally, the data demonstrated that
      xenologous transplantation of hMSCs could be considered as an ideal candidate for
      treatment of neurodegenerative diseases, especially HD. 

PMID- 25376131
TI  - Cortisol reactivity to social stress as a mediator of early adversity on risk and
      adaptive outcomes.
AB  - Children chronically exposed to stress early in life are at increased risk for
      maladaptive outcomes, though the physiological mechanisms driving these effects
      are unknown. Cortisol reactivity was tested as a mediator of the relation between
      prenatal substance exposure and/or early adversity on adaptive and maladaptive
      outcomes. Data were drawn from a prospective longitudinal study of prenatal
      substance exposure (N = 860). Cortisol reactivity was assessed at age 11. Among
      African Americans, prenatal substance exposure exerted an indirect effect through
      early adversity and cortisol reactivity to predict externalizing behavior,
      delinquency, and a positive student-teacher relationship at age 11. Decreased
      cortisol reactivity was related to maladaptive outcomes, and increased cortisol
      reactivity predicted better executive functioning and a more positive student
      teacher relationship. 

PMID- 25376133
TI  - Serial 3 T magnetic resonance imaging during cabergoline treatment of
      macroprolactinomas.
AB  - OBJECTIVE: Cabergoline is the treatment of choice for prolactin (PRL)-producing
      pituitary adenomas, because of its efficacy in normalizing PRL levels, and
      inducing tumor shrinkage. The clinical use of 3 T magnetic resonance imaging
      (MRI) for neuroimaging has rapidly expanded in recent years. In particular, T2
      weighted imaging (T2WI) provides high anatomical and contrast resolution.
      PATIENTS AND METHODS: In this study, serial 3 T MRI with T2WI was utilized during
      cabergoline treatment of 10 patients with macroprolactinomas. Cabergoline was
      started at a standard weekly dosage and incrementally adjusted on individual
      posttreatment PRL values. RESULTS: MRI confirmed tumor shrinkage in all patients
      during cabergoline treatment. Cabergoline normalized hyperprolactinemia in all
      but one patient. In six of 10 patients, distinct low-signal-intensity areas were
      evident throughout the adenomas on T2WI. In four of those six patients, massive
      low-signal-intensity areas appeared at 1-4 months, after which tumors decreased
      in size by over 80%. These findings in the early phase of prolactinoma treatment
      predicted pronounced regression or near-complete disappearance of the tumor.
      Reduction of T2 intensity possibly reflected dehydration due to diffuse
      hemorrhage in the adenomas. CONCLUSION: T2-weighted 3 T MR images are valuable
      for assessing and monitoring cabergoline treatment of macroprolactinomas.

PMID- 25376134
TI  - Academic self-concept in children with epilepsy and its relation to their quality
      of life.
AB  - OBJECTIVES: Academic achievement in children with epilepsy is a highly studied
      topic with many important implications. However, only little attention has been
      devoted to academic self-concept of such children and the relation of academic
      self-concept to their quality of life. We aimed to examine academic self-concept
      in children with epilepsy, to assess its relationship to academic achievement and
      to determine possible correlations between academic self-concept and quality of
      life. METHODS: The study group consisted of 182 children and adolescents aged 9
      14 years who completed the student's perception of ability scale (SPAS)
      questionnaire to determine their academic self-concept and the modified Czech
      version of the CHEQOL-25 questionnaire to determine their health-related quality
      of life. RESULTS: We found that academic self-concept in children with epilepsy
      was on average significantly lower than in their peers without seizures,
      especially with regard to general school-related abilities, reading, and
      spelling. On the other hand, the variance in the data obtained from the group of
      children with epilepsy was significantly higher than in the whole population and
      the proportion of individuals with very high academic self-concept seems
      comparable among children with and without epilepsy. Moreover, it was found that
      correlations between academic self-concept and academic achievement are
      significantly lower in children with epilepsy than in the whole population.
      DISCUSSION: The presented results suggest that considerable attention should be
      paid to the role of academic self-concept in education of children with epilepsy
      and to the factors influencing this self-concept in this group.

PMID- 25376135
TI  - FokI vitamin D receptor gene polymorphism in association with multiple sclerosis
      risk and disability progression in Slovaks.
AB  - OBJECTIVE: It is still unclear as to why multiple sclerosis (MS) is so
      devastating and rapidly progressive in one patient and less so in another. Recent
      data implicate vitamin D in modulation of the risk as well as the clinical course
      of disease. Since vitamin D acts through the vitamin D receptor (VDR),
      association of single nucleotide polymorphisms (SNPs) in the VDR gene might
      account for variations in the MS risk within populations. The aim of our study
      was to determine the association between FokI gene polymorphism (rs10735810) and
      the risk of MS in a cohort of Slovak population and to investigate possible
      correlations of this SNP with the rate of disease disability progression.
      METHODS: FokI SNP was detected in 270 clinically diagnosed MS patients and 303
      healthy control subjects. Genotyping was performed by polymerase chain reaction
      (PCR) and restriction analysis. We used multiple sclerosis severity score (MSSS)
      for patient's stratification by the rate of disease disability progression.
      RESULTS: We observed a significantly higher frequency of Ff genotype of FokI SNP
      (53.4 vs 43.7%, P  =  0.042) in women with MS compared to women of the control
      group. There was no significant association between FokI SNP and the rate of
      disease disability progression. DISCUSSION: Although our findings suggest a weak
      association between VDR SNP FokI and the MS risk in women, further studies are
      needed to explore the role of VDR polymorphic alterations in MS disease etiology
      and pathogenesis.

PMID- 25376136
TI  - Salvage of the condylar fracture: complication management of mandibular angle
      ostectomy.
AB  - A prominent mandibular angle is considered to be unattractive in Asians because
      it gives the face a square, coarse, and muscular appearance. Mandibular angle
      ostectomy has been known to be effective and to satisfy both surgeons and
      patients. However, a narrow surgical field hinders direct view of the site,
      making a procedure that is rather difficult to perform. Despite thorough
      presurgical planning and attention, there can be many complications and
      unfavorable results. A 21-year-old woman with right condyle process fracture was
      referred to Kyung Hee University Hospital at Gangdong. The patient was previously
      treated with mandibular angle reduction surgery at a local clinic. Via an
      extraoral approach, the condyle process was replaced and fixed using 1 long metal
      screw and one 2 * 2 square metal plate. We overcame the condylar fracture caused
      by mandibular angle ostectomy with reasonable reduction of the right condyle. 

PMID- 25376137
TI  - Huge nasopharyngeal teratoma with a cleft palate and bifid tongue in a patient
      with pierre robin syndrome.
AB  - PURPOSE: Nasopharyngeal teratoma is a very rare neoplasm that develops on the
      oronasal cavity as an expanding and cavity-filling lesion. We present a rare case
      of nasopharyngeal teratoma associated with a cleft palate and bifid tongue in a
      patient with Pierre Robin syndrome. METHODS: A preterm male neonate of 33 weeks
      and 6 days was referred to our department. A protruding solid mass with
      approximately 7.0 * 4.0-cm size arising from the vomer and combined cleft palate
      and tongue covered with pinkish skin with lanugo were observed. In addition,
      there was a bandlike tissue connecting vomer and sublingual area, which divided
      and restricted the anterior portion of the tongue. RESULTS: An early surgical
      intervention was decided because of problems with airways and nutrition caused by
      the mass. The mass was completely removed from the vomer. The histologic
      examination of the mass was consistent with mature teratoma. After his first
      operation, he was finally diagnosed with the Pierre Robin syndrome. After 4
      months, a tongue reduction was conducted for macroglossia, and after 9 months,
      remnant teratoma excision and a palate repair were conducted using 2-flap
      palatoplasty. CONCLUSIONS: A nasopharyngeal teratoma is a rare case and induces a
      cleft palate and bifid tongue in a preterm infant, leading to severe airway and
      nutritional problems. A teratoma interferes with the fusion of embryonic tissues
      in the early developmental period, in particular, with the palatal fusion
      severely prevented if the teratoma is accompanied by a Pierre Robin syndrome such
      as in this case.

PMID- 25376138
TI  - Need for airbag and seatbelt to reduce orbital injuries from steering wheel knob.
AB  - The aims of this study are to report a blowout fracture of the orbital floor and
      medial wall caused by being struck by a steering wheel knob of an automobile and
      to discuss the use of airbags and seatbelts as a preventive measure for orbital
      injuries. A 58-year-old man was struck in the left eye by a steering wheel. His
      car hit a telephone pole, and he had a frontal collision injury. In this frontal
      impact, his left eye was hit by a Brodie knob attached to the steering wheel. At
      the time of injury, the speed of the car was about 65 km/h. He was not wearing a
      seatbelt, and the airbag had not deployed. Swelling and ecchymosis were observed
      at the left periorbital area, and he had diplopia on a left-side gaze. A CT
      revealed fractures in the medial and inferior wall of the left orbit. Entrapped
      soft tissues were reduced, and the medial wall and floor were reconstructed with
      a resorbable sheet. His diplopia disappeared 12 days after surgery. To prevent
      the injury from the steering wheel knob, an airbag should be installed in any
      vehicle, which has a steering wheel knob. Legislation mandating the use of
      airbags as well as seatbelts in vehicles with attached steering wheel knobs
      should be made.

PMID- 25376139
TI  - Aspiration pneumonia associated with a double fracture of the mandible.
AB  - Aspiration pneumonia is one of the most life-threatening diseases in the elderly.
      A 73-year-old woman was diagnosed with aspiration pneumonia after a mandibular
      fracture. Because her persistent aspiration pneumonia was accompanied by a
      diminished swallowing function that was believed to be due to a double fracture
      of the mandible, the patient underwent an open reduction while having pneumonia.
      Her symptoms of aspiration pneumonia improved immediately after the surgery. The
      hyoid bone was repositioned to its original position, and the movements of the
      hyoid bone and mandible were recovered after the surgery. In cases in which the
      medial bone segment of the mandible moves inside because of a double fracture and
      the movement of the hyoid bone declines, we strongly suggest that an open
      reduction should be performed as soon as possible to prevent aspiration pneumonia
      caused by a swallowing dysfunction.

PMID- 25376140
TI  - Outcomes of arthrocentesis for the treatment of internal derangement pain: with
      or without corticosteroids?
AB  - PURPOSE: Arthrocentesis (AC) is an acceptable treatment modality in the treatment
      of internal derangement (ID) pain. This study evaluated outcomes of AC on pain
      relief of ID pain with or without corticosteroids. MATERIALS AND METHODS: This
      single-blind clinical trial was conducted on 60 patients with ID pain who were
      randomly assigned to 2 groups (30 in each group) for AC. The AC of the upper
      joint space was then performed by using Ringer lactate under local anesthesia in
      both groups. In the second group, the procedure was followed by the
      administration of a single-dose intra-articular dexamethasone (8 mg). Assessments
      were made at baseline (T0), 1 month (T1), and 6 months (T6) after AC; pain,
      maximum mouth opening, and joint sounds before and after treatment up to 6 months
      were evaluated. Pain severity was documented according to Visual Analogue Scale.
      Age, sex, and skeletal maxillomandibular relationship were considered as variable
      factors, and irrigation with or without corticosteroids was a predictive factor
      of the study. Pain, click, and maximum mouth opening were other assessment
      outcomes of the study. RESULTS: Comparison of age, sex, and skeletal relationship
      did not show any significant differences between the 2 groups. Results did not
      demonstrate any difference for click between the 2 groups. Comparison of pain
      severity in T0, T1, and T2 between the 2 groups did not show any significant
      differences (P < 0.05). The repeat measure test revealed a significant change in
      T0, T1, and T2 for both groups (P < 0.001). MMO significantly changed between T0
      and T1 and T0 and T6 in the 2 groups without any significant differences between
      them. CONCLUSIONS: The AC is an effective procedure for a short-term reduction of
      pain in temporomandibular disorder cases. It seems that AC using Ringer solution
      with or without corticosteroids may have the same effect on pain relief.

PMID- 25376141
TI  - Surgical management of immature teratoma involving the oral cavity and orbit in a
      neonate.
AB  - Teratomas are congenital germ cell tumors composed of elements from 1 or more of
      the embryonic germ layers and contain tissues usually foreign to the anatomic
      site of origin. In the head and neck region, these lesions are rare, and 90% of
      head and neck teratomas present during the neonatal and infantile periods.
      Besides, in neonates, it carries serious risk for respiratory distress as well as
      feeding problems due to oral cavity and airway obstruction.Here, an unusual case
      of intraoral teratoma involving the orbit in a newborn who underwent immediate
      surgical excision successfully is described. 

PMID- 25376142
TI  - Comparative treatment outcomes of menopausal and nonmenopausal women after
      arthrocentesis.
AB  - OBJECTIVES: Most of the patients treated for temporomandibular joint disorders
      constituted from the female population, and this situation is generally
      hypothesized and demonstrated in several studies. Arthrocentesis of the
      temporomandibular joint is a minimally invasive and effective treatment method in
      the management of patients with stage III and stage IV Wilkes syndrome. This
      study was aimed at assessing the effectiveness of this method between menopausal
      and nonmenopausal female patients. STUDY DESIGN: A total of 59 patients (25
      menopausal and 34 nonmenopausal) were evaluated according to the visual analog
      scale for pain and chewing function scores, joint sound, and maximum mouth
      opening. RESULTS: In both groups, the parameters were detected statistically
      significant according to follow-up periods. The menopausal group showed better
      results than the nonmenopausal group at 6-month controls. CONCLUSION: In
      conclusion, arthrocentesis is a satisfactory treatment modality in the management
      of temporomandibular joint derangements. Female reproductive hormone levels may
      affect the success of this procedure.

PMID- 25376143
TI  - Bilateral condylar resorption in down syndrome.
AB  - Asymptomatic idiopathic condylar resorption is a rare disease of difficult
      diagnosis and treatment. We review the literature about this rare condition and
      report a case of a patient, affected by Down syndrome, who underwent a complete
      untreated bilateral condylar resorption in adolescence and then developed pain on
      chewing only 20 years later. Despite a precise orthodontic and surgical
      therapeutic plan, treatment had to be discontinued because of patient lack of
      compliance. This case is the first of its kind to be reported and emphasizes the
      need for special attention in patients with disability. 

PMID- 25376144
TI  - Clinical study comparing alveolar distraction using the lead system and MODUS MDO
      1.5/2.0.
AB  - This article compares 2 different alveolar distractors: Lead System (LS) and
      MODUS MDO 1.5/2.0 (M-MDO). This is a clinical retrospective study; 32
      distractions were performed. We used the LS distractor (intraosseous) on 24
      patients and the M-MDO (extraosseous) on the other 8. The variables included bone
      alveolar ridge height, alterations of the oral mucosa, number of distractors,
      implant survival, and complications. We also developed descriptive and univariate
      statistical analysis. The mean increase of bone height after performing the
      alveolar distraction was 6.15 mm, 5.74 mm with LS, and 8.36 mm with M-MDO (P <
      0.0001). The survival rates of the implants in the intraosseous and extraosseous
      groups reached 100%. However, the use of M-MDO resulted in a significant defect
      in the alveolar mucosa during implant insertion (100%), an event that did not
      occur when using LS (P < 0.001). The most common complication in the intraosseous
      group was the tilting of the segment (25%), whereas, in the extraosseous group,
      the main difficulty was the rod interference with the opposing arch (75%). Bone
      defects after alveolar distraction appeared both in the intraosseous group
      (66.7%) and in the extraosseous group (50%). Both the LS and the M-MDO
      distractors are effective for alveolar bone distraction. The choice of one
      distractor over another depends on the clinical characteristics of each case,
      such as the size and shape of the defect, the patient's tolerance, the distance
      to the opposing arch, and the surgeon's experience. 

PMID- 25376145
TI  - Craniofacial reconstruction with poly(methyl methacrylate) customized cranial
      implants.
AB  - BACKGROUND: Secondary cranioplasty with customized craniofacial implants (CCIs)
      are often used to restore cerebral protection and reverse syndromes of the
      trephined, and for reconstruction of acquired cranial deformities. The 2 most
      widely used implant materials are polyetheretherketone and
      poly(methylmethacrylate) (PMMA). Previous series with CCIs report several major
      complications, including implant infection leading to removal, extended hospital
      stays, and surgical revisions. With this in mind, we chose to review our large
      case series of 22 consecutive PMMA CCI cranioplasties treated by a single
      craniofacial surgeon. METHODS: A cohort of 20 consecutive patients receiving 22
      PMMA implants during a 2-year period was identified and outcomes reviewed. The
      mechanism of initial insult, time from craniectomy to cranioplasty, anesthesia
      time, major and minor postoperative complications, radiation history, and length
      of follow-up were statistically analyzed. RESULTS: There were no complications
      related to infection, hematoma/seroma, or cerebrospinal fluid leak (0/22, 0%).
      Two patients experienced major complications related to persistent temporal
      hollowing (PTH) following standard CCI cranioplasty, which required revision
      surgery with modified implants (2/22, 9%). One minor complication of self
      resolving transient diplopia was noted (1/22, 5%). CONCLUSIONS: In this
      consecutive series, PMMA CCIs were associated with a very low complication rate,
      suggesting that PMMA may be a preferred material for CCI fabrication. However,
      with 10% (2/20) of patients experiencing PTH and dissatisfaction related to
      asymmetry, future research must be directed at modifying CCI shape, to address
      the overlying soft-tissue deformity. If successful, this may increase patient
      satisfaction, prevent PTH, and avoid additional costs of revision surgery.

PMID- 25376146
TI  - Three gangliogliomas: results of GTG-banding, SKY, genome-wide high resolution
      SNP-array, gene expression and review of the literature.
AB  - According to the World Health Organization gangliogliomas are classified as well
      differentiated and slowly growing neuroepithelial tumors, composed of neoplastic
      mature ganglion and glial cells. It is the most frequent tumor entity observed in
      patients with long-term epilepsy. Comprehensive cytogenetic and molecular
      cytogenetic data including high-resolution genomic profiling (single nucleotide
      polymorphism (SNP)-array) of gangliogliomas are scarce but necessary for a better
      oncological understanding of this tumor entity. For a detailed characterization
      at the single cell and cell population levels, we analyzed genomic alterations of
      three gangliogliomas using trypsin-Giemsa banding (GTG-banding) and by spectral
      karyotyping (SKY) in combination with SNP-array and gene expression array
      experiments. By GTG and SKY, we could confirm frequently detected chromosomal
      aberrations (losses within chromosomes 10, 13 and 22; gains within chromosomes 5,
      7, 8 and 12), and identify so far unknown genetic aberrations like the unbalanced
      non-reciprocal translocation t(1;18)(q21;q21). Interestingly, we report on the
      second so far detected ganglioglioma with ring chromosome 1. Analyses of SNP
      array data from two of the tumors and respective germline DNA (peripheral blood)
      identified few small gains and losses and a number of copy-neutral regions with
      loss of heterozygosity (LOH) in germline and in tumor tissue. In comparison to
      germline DNA, tumor tissues did not show substantial regions with significant
      loss or gain or with newly developed LOH. Gene expression analyses of tumor
      specific genes revealed similarities in the profile of the analyzed samples
      regarding different relevant pathways. Taken together, we describe overlapping
      but also distinct and novel genetic aberrations of three gangliogliomas.

PMID- 25376147
TI  - Indium-catalyzed intramolecular hydroarylation of aryl propargyl ethers.
AB  - Indium(III) halides catalyze efficiently the intramolecular hydroarylation (IMHA)
      of aryl propargyl ethers. The reaction proceeds regioselectively with terminal
      and internal alkynes bearing electron-rich and electron-deficient substituents in
      the benzenes and alkynes affording only the 6-endo dig cyclization product.
      Additionally, a sequential indium-catalyzed IMHA and palladium-catalyzed
      Sonogashira coupling can be performed in one reaction vessel. Experiments with
      deuterium support a mechanism through electrophilic aromatic substitution.

PMID- 25376148
TI  - Environmental contaminants and chromosomal damage associated with beak
      deformities in a resident North American passerine.
AB  - A large cluster of beak abnormalities among black-capped chickadees (Poecile
      atricapillus) in Alaska raised concern about underlying environmental factors in
      this region. Metals and trace elements, organochlorine pesticides,
      polychlorinated biphenyls (PCBs), and polychlorinated dibenzo-dioxins and
      polychlorinated dibenzofurans (PCDD-Fs) were analyzed in adults, nestlings, and
      eggs of the affected population; local bird seed was also tested for
      organochlorine pesticides. The results offered no support for the hypothesis that
      selenium or any other inorganic element was responsible for beak deformities
      among chickadees, but some evidence that organochlorine compounds may be
      contributing factors. Adults with beak deformities had an elevated level of
      chromosomal damage, which was correlated with lipid level and concentrations of
      several organochlorine compounds. Multivariate analyses of pesticides and PCBs
      did not distinguish abnormal from normal adults, but subsequent univariate
      analysis demonstrated higher concentrations of heptachlor epoxide and PCB-123 in
      abnormal adults. Concentrations of all organochlorine compounds were low, and
      none is known to cause beak or keratin abnormalities. Patterns of PCB congener
      concentrations differed between nestlings with normal and abnormal parents. Eggs
      from clutches with low hatchability had higher concentrations of
      hexachlorobenzene and PCDD-Fs than those with high hatching success, and
      hexachlorobenzene was found in seeds. Additional testing for PCDD-Fs, polycyclic
      aromatic hydrocarbons, and other emerging contaminants, including brominated
      compounds, is needed to rule out environmental contaminants as a cause of beak
      deformities in chickadees in Alaska.

PMID- 25376149
TI  - Effects of intra-aortic balloon pump counterpulsation on left ventricular
      mechanoenergetics in a porcine model of acute ischemic heart failure.
AB  - We investigated the effects of intra-aortic balloon pump (IABP) counterpulsation
      on left ventricular (LV) contractility, relaxation, and energy consumption and
      probed the underlying physiologic mechanisms in 12 farm pigs, using an ischemia
      reperfusion model of acute heart failure. During both ischemia and reperfusion,
      IABP support unloaded the LV, decreased LV energy consumption (pressure-volume
      area, stroke work), and concurrently improved LV mechanical performance (ejection
      fraction, stroke volume, cardiac output). During reperfusion exclusively, IABP
      also improved LV relaxation (tau) and contractility (Emax, PRSW). The beneficial
      effects of IABP support on LV relaxation and contractility correlated with IABP
      induced augmentation of coronary blood flow. In conclusion, we find that during
      both ischemia and reperfusion, IABP support optimizes LV energetic performance
      (decreases energy consumption and concurrently improves mechanical performance)
      by LV unloading. During reperfusion exclusively, IABP support also improves LV
      contractility and active relaxation, possibly due to a synergistic effect of
      unloading and augmentation of coronary blood flow. 

PMID- 25376150
TI  - Effect of aqueous ethanol on the triple helical structure of collagen.
AB  - Collagen, the most abundant protein in mammals, is widely used for making
      biomaterials. Recently, organic solvents have been used to fabricate collagen
      based biomaterials for biological applications. It is therefore necessary to
      understand the behavior of collagen in the presence of organic solvents at low
      (<=50%, v/v) and high (>=90%, v/v) concentrations. This study was conducted to
      examine how collagen reacts when exposed to low and high concentrations of
      ethanol, one of the solvents used to make collagen-based biomaterials. Solubility
      testing indicated that collagen remains in solution at low concentrations (<=50%,
      v/v) of ethanol but precipitates (gel-like) thereafter, irrespective of the
      method of addition of ethanol (single shot or gradual addition); this behavior is
      different from that observed recently with acetonitrile. Collagen retains its
      triple helix in the presence of ethanol but becomes thermodynamically unstable,
      with substantially reduced melting temperature, with increasing concentration of
      ethanol. It was also found that the CD ellipticity at 222 nm, characteristic of
      the triple-helical structure, does not correlate with the thermal stability of
      collagen. Time-dependent experiments reveal that the collagen triple helix is
      kinetically stable in the presence of 0-40% (v/v) ethanol at low temperature (5 
      degrees C) but highly unstable in the presence of ethanol at elevated temperature
      (~34  degrees C). These results indicate that when ethanol is used to process
      collagen-based biomaterials, such factors as temperature and duration should be
      done taking into account, to prevent extensive damage to the triple-helical
      structure of collagen.

PMID- 25376151
TI  - Computational simulation of the adaptive capacity of vein grafts in response to
      increased pressure.
AB  - Vein maladaptation, leading to poor long-term patency, is a serious clinical
      problem in patients receiving coronary artery bypass grafts (CABGs) or undergoing
      related clinical procedures that subject veins to elevated blood flow and
      pressure. We propose a computational model of venous adaptation to altered
      pressure based on a constrained mixture theory of growth and remodeling (G&R). We
      identify constitutive parameters that optimally match biaxial data from a mouse
      vena cava, then numerically subject the vein to altered pressure conditions and
      quantify the extent of adaptation for a biologically reasonable set of bounds for
      G&R parameters. We identify conditions under which a vein graft can adapt
      optimally and explore physiological constraints that lead to maladaptation.
      Finally, we test the hypothesis that a gradual, rather than a step, change in
      pressure will reduce maladaptation. Optimization is used to accelerate parameter
      identification and numerically evaluate hypotheses of vein remodeling. 

PMID- 25376152
TI  - Hydrothermal combination of trilacunary Dawson phosphotungstates and hexanickel
      clusters: from an isolated cluster to a 3D framework.
AB  - Three novel hexa-Ni-substituted Dawson phosphortungstates [Ni6 (en)3 (H2O)6 (MU3
      OH)3 (H3 P2 W15 O56 )]?14 H2O (1), [Ni(enMe)2 (H2O)][Ni6 (enMe)3 (MU3-OH)3 (H2O)6
      (HP2 W15 O56)]? 10 H2O (2), and [Ni(enMe)2 ]3 [Ni(enMe)2
      (H2O)][Ni(enMe)(H2O)2][Ni6 (enMe)3 (MU3-OH)3 (Ac)2 (H2O)(P2 W15 O56)]2 ?6 H2O (3)
      (en=ethylenediamine, enMe=1, 2-diaminopropane, Ac=CH3 COO(-)) have been made
      under hydrothermal conditions and were characterized by IR spectroscopy,
      elemental analysis, diffuse reflectance spectroscopy, thermogravimetric analysis,
      powder X-ray diffraction, and single-crystal X-ray diffraction. The common
      structural features of compounds 1-3 contain the similar hexa-Ni-substituted
      Dawson polyoxometalate (POM) units that can be viewed as a [Ni6 (MU3-OH)3](9+)
      cluster capping on a [P2 W15 O56](12-) fragment. Compounds 1 and 2 are two
      isolated clusters, whereas compound 3 is the first 3D POM framework constructed
      from hexa-Ni-substituted Dawson POM units and Ni(enMe) complex bridges. The
      preparations of compounds 1-3 not only indicate that triangle coplanar Ni6
      clusters are very stable fragments in both trivacant Keggin and trivacant Dawson
      POM systems, but also offer that the hydrothermal technique can act as an
      effective strategy for making novel Dawson-type high-nuclear transition-metal
      cluster substituted POMs by combination of lacunary Dawson precusors with
      transition-metal cations in the tunable role of organic ligands. In addition,
      magnetic measurements illustrate that there exist overall ferromagnetic
      interactions in compound 3.

PMID- 25376153
TI  - High-Performance Blue/Ultraviolet-Light-Sensitive ZnSe-Nanobelt Photodetectors.
AB  - Single-crystalline zinc selenide (ZnSe) nanobelts were fabricated via the
      ethylenediamine (en)-assisted ternary solution technique and subsequent thermal
      treatment. Individual ZnSe nanobelts were assembled into nanoscale devices,
      showing a high spectral selectivity and photocurrent/immediate-decay ratio and a
      fast time response, justifying effective utilization of the ZnSe nanobelts as
      blue/UV-light-sensitive photodetectors. 

PMID- 25376154
TI  - Diamond nanowires: fabrication, structure, properties, and applications.
AB  - C(sp(3) )?C-bonded diamond nanowires are wide band gap semiconductors that
      exhibit a combination of superior properties such as negative electron affinity,
      chemical inertness, high Young's modulus, the highest hardness, and room
      temperature thermal conductivity. The creation of 1D diamond nanowires with their
      giant surface-to-volume ratio enhancements makes it possible to control and
      enhance the fundamental properties of diamond. Although theoretical comparisons
      with carbon nanotubes have shown that diamond nanowires are energetically and
      mechanically viable structures, reproducibly synthesizing the crystalline diamond
      nanowires has remained challenging. We present a comprehensive, up-to-date review
      of diamond nanowires, including a discussion of their synthesis along with their
      structures, properties, and applications. 

PMID- 25376155
TI  - Sex-specific effects of prenatal and postnatal nutritional conditions on the
      oxidative status of great tit nestlings.
AB  - The early life period is characterized by fast growth and development, which can
      lead to high reactive oxygen species (ROS) production. Young animals thus have to
      balance their investment in growth versus ROS defence, and this balance is likely
      mediated by resource availability. Consequently resources transferred prenatally
      by the mother and nutritional conditions experienced shortly after birth may
      crucially determine the oxidative status of young animals. Here, we
      experimentally investigated the relative importance of pre- and early postnatal
      nutritional conditions on the oxidative status of great tit nestlings (Parus
      major). We show that resources transferred by the mother through the egg and
      nutritional conditions encountered after hatching affect the oxidative status of
      nestling in a sex-specific way. Daughters of non-supplemented mothers and
      daughters which did not receive extra food during the early postnatal period had
      higher oxidative damage than sons, while no differences between sons and
      daughters were found when extra food was provided pre- or postnatally. No effect
      of the food supplementations on growth, fledging mass or tarsus length was
      observed, indicating that female nestlings maintained their investment in growth
      at the expense of ROS defence mechanisms when resources were limited. The lower
      priority of the antioxidant defence system for female nestlings was also
      evidenced by lower levels of specific antioxidant components. These results
      highlight the important role of early parental effects in shaping oxidative
      stress in the offspring, and show that the sensitivity to these parental effects
      is sex-specific. 

PMID- 25376156
TI  - Direct determination of fatty acids in fish tissues: quantifying top predator
      trophic connections.
AB  - Fatty acids are a valuable tool in ecological studies because of the large number
      of unique structures synthesized. They provide versatile signatures that are
      being increasingly employed to delineate the transfer of dietary material through
      marine and terrestrial food webs. The standard procedure for determining fatty
      acids generally involves lipid extraction followed by methanolysis to produce
      methyl esters for analysis by gas chromatography. By directly transmethylating
      ~50 mg wet samples and adding an internal standard it was possible to greatly
      simplify the analytical methodology to enable rapid throughput of 20-40 fish
      tissue fatty acid analyses a day including instrumental analysis. This method was
      verified against the more traditional lipid methods using albacore tuna and great
      white shark muscle and liver samples, and it was shown to provide an estimate of
      sample dry mass, total lipid content, and a condition index. When large fatty
      acid data sets are generated in this way, multidimensional scaling, analysis of
      similarities, and similarity of percentages analysis can be used to define
      trophic connections among samples and to quantify them. These routines were used
      on albacore and skipjack tuna fatty acid data obtained by direct methylation
      coupled with literature values for krill. There were clear differences in fatty
      acid profiles among the species as well as spatial differences among albacore
      tuna sampled from different locations.

PMID- 25376157
TI  - Measuring habitat heterogeneity reveals new insights into bird community
      composition.
AB  - Fine-scale vegetation cover is a common variable used to explain animal
      occurrence, but we know less about the effects of fine-scale vegetation
      heterogeneity. Theoretically, fine-scale vegetation heterogeneity is an important
      driver of biodiversity because it captures the range of resources available in a
      given area. In this study we investigated how bird species richness and birds
      grouped by various ecological traits responded to vegetation cover and
      heterogeneity. We found that both fine-scale vegetation cover (of tall trees,
      medium-sized trees and shrubs) and heterogeneity (of tall trees, and shrubs) were
      important predictors of bird richness, but the direction of the response of bird
      richness to shrub heterogeneity differed between sites with different proportions
      of tall tree cover. For example, bird richness increased with shrub heterogeneity
      in sites with high levels of tall tree cover, but declined in sites with low
      levels of tall tree cover. Our findings indicated that an increase in vegetation
      heterogeneity will not always result in an increase in resources and niches, and
      associated higher species richness. We also found birds grouped by traits
      responded in a predictable way to vegetation heterogeneity. For example, we found
      small birds benefited from increased shrub heterogeneity supporting the textual
      discontinuity hypothesis and non-arboreal (ground or shrub) nesting species were
      associated with high vegetation cover (low heterogeneity). Our results indicated
      that focusing solely on increasing vegetation cover (e.g. through restoration)
      may be detrimental to particular animal groups. Findings from this investigation
      can help guide habitat management for different functional groups of birds. 

PMID- 25376159
TI  - Hepatic fat, not visceral fat, is associated with gallbladder polyps: a study of
      2643 healthy subjects.
AB  - BACKGROUND AND AIM: Gallbladder polyps (GBPs) appear to be strongly associated
      with obesity and metabolic disease. To date, the relationship between GBPs and
      fatty liver has not been adequately evaluated. The aim of the present study was
      to investigate whether GBPs are associated with fatty liver, which is an ectopic
      regional fat deposit, independent of visceral adipose tissue (VAT). METHODS: A
      cross-sectional study using 2643 health checkup subjects (961 patients with GBP
      and 1682 age- and sex-matched healthy controls) was conducted. The subjects
      underwent various laboratory tests, abdominal fat computed tomography (CT), and
      hepatic ultrasonography. RESULTS: The mean age of the subjects was 51.4 +/- 8.3
      years, and 74.1% were male. GBPs were significantly associated with fatty liver.
      Multivariate regression analysis revealed that GBPs were significantly associated
      with the presence of fatty liver (odds ratio [OR] 1.23, 95% confidence interval
      [CI]: 1.02-1.48), and adjusting for the homeostatic metabolic assessment index
      had little effect on this association (OR 1.23, 95% CI: 1.02-1.48). Additionally,
      GBPs remained significantly associated with the presence of fatty liver after
      adjustments for CT-measured VAT and subcutaneous adipose tissue (OR 1.24, 95% CI:
      1.03-1.50). The degree of fatty liver showed an independent (OR 1.37 95% CI: 1.03
      1.80) and dose-dependent relationship (moderate-severe fatty liver: OR 1.55 95%
      CI: 1.07-2.23, P for trend = 0.014) with large GBPs (>= 5 mm). CONCLUSION: Fatty
      liver, an ectopic regional fat deposit, was found to be closely associated with
      GBPs independent of known metabolic risk factors, insulin resistance, and CT
      measured VAT, confirming a relevant clinical relationship between the two
      diseases.

PMID- 25376158
TI  - Effect of heat-assisted pulsed electric fields and bacteriophage on
      enterohemorrhagic Escherichia coli O157:H7.
AB  - Pulsed electric fields (PEF), heat-assisted PEF (H-PEF), and virulent
      bacteriophage (VP) are non-thermal techniques for pathogen inactivation in
      liquids that were investigated individually, and in combination (PEF/VP, H
      PEF/VP) to control enterohemorrhagic Escherichia coli (EHEC) O157:H7 in Luria
      Bertani broth (LBB) and Ringer's solution (RS). Treated cells were subsequently
      incubated at refrigeration (4 degrees C) and temperature-abuse conditions (12
      degrees C) for 5 days. When EHEC cells grown in LBB were subjected to non-thermal
      processing and subsequently stored at 12 degrees C for 5 days, reductions in
      count of between 0.1 and 0.6 log cycles were observed and following storage at 4
      degrees C the decrease in counts varied between 0.2 and 1.1 log10 . For bacteria
      cells suspended in RS values ranged from 0.1 to >=3.9 log cycles at both storage
      temperatures. The most effective treatments were H-PEF and H-PEF/VP, both
      producing a >3.4 log cycle reduction of cells suspended in non-nutrient RS.
      Analysis of EHEC recovery on selective and non-selective media indicated no
      occurrence of sub-lethal damage for VP, PEF/VP, and H-PEF/VP-treated cells. The
      findings indicate that combining PEF and lytic phage may represent a suitable
      alternative to conventional fluid decontamination following further process
      optimization.

PMID- 25376160
TI  - Efficacy and safety of prolonged-release trazodone in major depressive disorder:
      a multicenter, randomized, double-blind, flexible-dose trial.
AB  - OBJECTIVE: To investigate the efficacy, safety, and clinical benefit of prolonged
      release trazodone (Trittico) in the treatment of major depressive disorder (MDD).
      METHODS: In this study, 363 Chinese patients with MDD were randomized 1:1 to
      receive either prolonged-release trazodone (150-450 mg) or placebo treatment for
      6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton
      Depression Rating Scale (HAMD-17) total score from baseline to the end of the
      study. The secondary efficacy measurements were the response and remission rates,
      the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end
      of the study, and the change of the HAMD-14 total score and quality of sleep
      [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study
      period. RESULTS: The mean maximum daily dose was 273.11 mg for the trazodone
      group and 290.92 mg for the placebo group. At the end of the study, there was a
      significant difference between the two groups in the HAMD-17 change score
      (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages
      at 1 week of treatment, and the effect lasted until the end of the study (week
      6). The response and remission rates of the trazodone group were significantly
      higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001;
      remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions
      of trazodone were mild to moderate, and the most frequent adverse reactions
      (>=5%) were dizziness, dry mouth, somnolence, and nausea. CONCLUSIONS: Prolonged
      release trazodone was more effective than placebo in MDD and was well tolerated.

PMID- 25376162
TI  - Is the molecular adsorbent recirculating system the answer for children with
      acute liver failure?

PMID- 25376161
TI  - New non-cognitive procedures for medical applicant selection: a qualitative
      analysis in one school.
AB  - BACKGROUND: Recent data have called into question the reliability and predictive
      validity of standard admission procedures to medical schools. Eliciting non
      cognitive attributes of medical school applicants using qualitative tools and
      methods has thus become a major challenge. METHODS: 299 applicants aged 18-25
      formed the research group. A set of six research tools was developed in addition
      to the two existing ones. These included: a portfolio task, an intuitive task, a
      cognitive task, a personal task, an open self-efficacy questionnaire and field
      notes. The criteria-based methodology design used constant comparative analysis
      and grounded theory techniques to produce a personal attributes profile per
      participant, scored on a 5-point scale holistic rubric. Qualitative validity of
      data gathering was checked by comparing the profiles elicited from the existing
      interview against the profiles elicited from the other tools, and by comparing
      two profiles of each of the applicants who handed in two portfolio tasks.
      Qualitative validity of data analysis was checked by comparing researcher results
      with those of an external rater (n =10). Differences between aggregated profile
      groups were checked by the Npar Wilcoxon Signed Ranks Test and by Spearman Rank
      Order Correlation Test. All subjects gave written informed consent to their
      participation. Privacy was protected by using code numbers. RESULTS: A concept
      map of 12 personal attributes emerged, the core constructs of which were
      motivation, sociability and cognition. A personal profile was elicited. Inter
      rater agreement was 83.3%. Differences between groups by aggregated profiles were
      found significant (p < .05, p < .01, p < .001).A random sample of sixth year
      students (n = 12) underwent the same admission procedure as the research group.
      Rank order was different; and arrogance was a new construct elicited in the sixth
      year group. CONCLUSIONS: This study suggests a broadening of the methodology for
      selecting medical school applicants. This methodology differentiates between both
      individuals and groups, providing a personal attribute profile of applicants,
      useful for admission procedures. The qualitative procedures are cost-effective,
      can easily be taught and used by faculty members. The predictive validity of the
      presented model requires a longitudinal trial.

PMID- 25376163
TI  - Phenotyping the quality of complex medium components by simple online-monitored
      shake flask experiments.
AB  - BACKGROUND: Media containing yeast extracts and other complex raw materials are
      widely used for the cultivation of microorganisms. However, variations in the
      specific nutrient composition can occur, due to differences in the complex raw
      material ingredients and in the production of these components. These lot-to-lot
      variations can affect growth rate, product yield and product quality in
      laboratory investigations and biopharmaceutical production processes. In the
      FDA's Process Analytical Technology (PAT) initiative, the control and assessment
      of the quality of critical raw materials is one key aspect to maintain product
      quality and consistency. In this study, the Respiration Activity Monitoring
      System (RAMOS) was used to evaluate the impact of different yeast extracts and
      commercial complex auto-induction medium lots on metabolic activity and product
      yield of four recombinant Escherichia coli variants encoding different enzymes.
      RESULTS: Under non-induced conditions, the oxygen transfer rate (OTR) of E. coli
      was not affected by a variation of the supplemented yeast extract lot. The
      comparison of E. coli cultivations under induced conditions exhibited tremendous
      differences in OTR profiles and volumetric activity for all investigated yeast
      extract lots of different suppliers as well as lots of the same supplier
      independent of the E. coli variant. Cultivation in the commercial auto-induction
      medium lots revealed the same reproducible variations. In cultivations with
      parallel offline analysis, the highest volumetric activity was found at different
      cultivation times. Only by online monitoring of the cultures, a distinct
      cultivation phase (e.g. glycerol depletion) could be detected and chosen for
      comparable and reproducible offline analysis of the yield of functional product.
      CONCLUSIONS: This work proves that cultivations conducted in complex media may be
      prone to significant variation in final product quality and quantity if the
      quality of the raw material for medium preparation is not thoroughly checked. In
      this study, the RAMOS technique enabled a reliable and reproducible screening and
      phenotyping of complex raw material lots by online measurement of the respiration
      activity. Consequently, complex raw material lots can efficiently be assessed if
      the distinct effects on culture behavior and final product quality and quantity
      are visualized.

PMID- 25376165
TI  - Exploring the kinetics of ordered silicon nanowires with the formation of
      nanogaps using metal-assisted chemical etching.
AB  - Actual dimension control of silicon (Si) nanowire arrays was conducted using
      metal-assisted chemical etching on Si patterned by electron beam lithography. The
      appearance of nanogaps at the edge of each nanowire provides the diffusion
      pathways of reactants for Si dissolution, predominantly causing distinct etching
      rates that depend upon the spacings of nanogaps. 

PMID- 25376164
TI  - Comparison of sole nurse and team-delivered community clozapine services for
      people with treatment-resistant schizophrenia.
AB  - AIM: To compare sole nurse and doctor-led multidisciplinary team delivery of
      community clozapine services for people with treatment-resistant schizophrenia.
      BACKGROUND: Around 20% of people with schizophrenia are treatment resistant and
      fail to respond to front line medications. Clozapine, a second-line treatment,
      has potentially serious side effects requiring regular monitoring. Different
      models of community clozapine services are emerging in the British National
      Health Service, but there is little evidence about which is best. DESIGN:
      Questionnaire survey of service users. METHODS: All patients on the lists of
      seven clozapine clinics (four sole nurse, three multidisciplinary team) in one
      trust were invited to participate, 2009-2010. Forward stepwise regression was
      used to investigate associations between patient well-being, functioning, self
      efficacy and satisfaction, and clinic model attended, controlling for socio
      demographic and health characteristics and processes of care. Use (and costs) of
      other health and social services accessed was compared between models. RESULTS:
      Sixty-six service users (35% participation rate) responded. Well-being and
      functioning were associated with patient characteristics and processes of care,
      not clinic model. Patients managed by sole nurses reported, over 3 months: more
      community psychiatric nurse visits and hospital psychiatrist appointments. Clinic
      list size affects costs per patient. CONCLUSIONS: Multidisciplinary team delivery
      may reduce use of other services. Although multidisciplinary team delivery is
      regarded as best practice, sole nurses can effectively provide clozapine services
      and may be warranted in areas of low population density.

PMID- 25376166
TI  - Reply to letter to the editor concerning: a variant pattern of Calretinin
      immunohistochemistry on rectal suction-biopsies is fully specific of short
      segment Hirschsprung's disease. Vincent Guinard-Samuel, Arnaud Bonnard, Michel
      Peuchmaur and Dominique Berrebi. Pediatr Surg Int (2014) 30: 803-808.

PMID- 25376167
TI  - Pharmacokinetics and penetration into synovial fluid of systemical and
      electroporation administered sinomenine to rabbits.
AB  - Sinomenine is an anti-rheumatoid arthritis (RA) drug derived from the Sinomenium
      acutum. The major site of RA treatment is within the synovial compartment.
      However, the pharmacokinetic and penetration into synovial fluid (SF) of
      sinomenine have not been reported. In our study, the pharmacokinetics and
      penetration into SF of systemic and electroporation administered sinomenine were
      investigated by microdialysis incorporated with HPLC-MS/MS. Sinomenine went into
      plasma and SF more rapidly with higher peak concentration (Cmax ) by
      intramuscular injection compared with oral administration. The area under the
      concentration-time graph (AUC0-infinity ) of intramuscularly injected sinomenine
      was 1,403,294.75 +/- 125,534.567 ng min/mL in plasma and 456,116.37 +/- 62,648.36
      ng min/mL in SF, which were equivalent with those for an oral dose. These results
      indicated that equal amounts of sinomenine could penetrate into SF by the two
      administration routes, and the permeation ratios were approximately 1:3. The AUC0
      infinity and Cmax were lower with electroporation compared with systemic
      administration, but the CSF /CPlasma (concentration of sinomenine in SF vs that
      of plasma) at 90, 120, 150, 180, 240 and 480 min by electroporation was 3- to 10
      fold higher relative to systemic administration. This illustrated that sinomenine
      can be targeted into joints by electroporation, and electroporation is a
      potential technique for sinomenine's transdermal delivery.

PMID- 25376168
TI  - Parasite evolution in response to sex-based host heterogeneity in resistance and
      tolerance.
AB  - Heterogenity between sexes in terms of both the level and the type of immune
      response to infection is documented in many species, but its role on parasite
      evolution is only beginning to be explored. We adopt an evolutionary epidemiology
      approach to study how the ability of a host to respond to infection through
      active immunity (resistance) or through minimizing deleterious effects of a given
      parasite load (tolerance) affects the evolution of parasite virulence.
      Consistently with earlier models, we find that increases in host resistance and
      tolerance both favour more virulent parasite strains. However, we show that
      qualitatively different results can be obtained if dimorphism between the sexes
      occurs through resistance or through tolerance depending on the contact pattern
      between the sexes. Finally, we find that variations in host sex ratio can amplify
      the consequences of heterogeneity for parasite evolution. These results are
      analysed in the light of several examples from the literature to illustrate the
      prevalence of sexually dimorphic immune responses and the potential for further
      study of the role of sexual dimorphism on parasite evolution. Such studies are
      likely to be highly relevant for improving treatment of chronic infections and
      control of infectious diseases, and understanding the role of sex in immune
      function. 

PMID- 25376170
TI  - Pharmacokinetics and pharmacodynamics of dermorphin in the horse.
AB  - Dermorphin is a MU-opioid receptor-binding peptide that causes both central and
      peripheral effects following intravenous administration to rats, dogs, and humans
      and has been identified in postrace horse samples. Ten horses were intravenously
      and/or intramuscularly administered dermorphin (9.3 +/- 1.0 MUg/kg), and plasma
      concentration vs. time data were evaluated using compartmental and
      noncompartmental analyses. Data from intravenous administrations fit a 2
      compartment model best with distribution and elimination half-lives (harmonic
      mean +/- pseudo SD) of 0.09 +/- 0.02 and 0.76 +/- 0.22 h, respectively. Data from
      intramuscular administrations fit a noncompartmental model best with a terminal
      elimination half-life of 0.68 +/- 0.24 (h). Bioavailability following
      intramuscular administration was variable (47-100%, n = 3). The percentage of
      dermorphin excreted in urine was 5.0 (3.7-10.6) %. Excitation accompanied by an
      increased heart rate followed intravenous administration only and subsided after
      5 min. A plot of the mean change in heart rate vs. the plasma concentration of
      dermorphin fit a hyperbolic equation (simple Emax model), and an EC(50) of 21.1
      +/- 8.8 ng/mL was calculated. Dermorphin was detected in plasma for 12 h and in
      urine for 48 or 72 h following intravenous or intramuscular administration,
      respectively.

PMID- 25376169
TI  - Sleep-disordered breathing and functional decline in older women.
AB  - OBJECTIVES: To determine the association between sleep-disordered breathing (SDB)
      and decline in instrumental activities of daily living (IADLs) and mobility in
      older women. DESIGN: Prospective cohort. SETTING: Minneapolis and Pittsburgh
      sites of the Study of Osteoporotic Fractures, participants' homes. PARTICIPANTS:
      Women with a mean age +/- standard deviation of 82.3 +/- 3.2 (N = 302).
      MEASUREMENTS: Participants completed a single night of unattended polysomnography
      and provided data regarding difficulty with IADLs and mobility. They repeated
      IADL and mobility measures 5.0 +/- 0.7 years later. RESULTS: After adjustment for
      age, obesity, Mini-Mental State Examination score, depressive symptoms, history
      of hypertension and chronic obstructive pulmonary disease, and number of IADL
      impairments at baseline, women with an apnea-hypopnea index (AHI) of 15 or
      greater at baseline had more than twice the odds of an increase in number of IADL
      difficulties (adjusted odds ratio (aOR) = 2.22, 95% confidence interval (CI) =
      1.09-4.53) and of incident IADL difficulty (aOR = 2.43, 95% CI = 1.00-5.92), of
      women with an AHI less than 5. There was no association between AHI and mobility
      difficulty. Women in the middle and highest tertiles of oxygen desaturation index
      had more than double the odds as those in the lowest tertile of an increase in
      number of IADL difficulties (middle tertile aOR = 2.64, 95% CI = 1.38-5.04,
      highest tertile aOR = 2.17, 95% CI = 1.13-4.17) and approximately three times the
      odds of incident IADL difficulty (middle tertile aOR = 2.84, 95% CI = 1.27-6.36,
      highest tertile aOR = 3.07, 95% CI = 1.31-7.18). Neither sleep fragmentation nor
      sleep duration was associated with IADL outcomes. CONCLUSION: SDB and associated
      hypoxemia are risk factors for functional decline in older women. Research is
      needed to determine whether treatment of SDB prevents functional decline.

PMID- 25376171
TI  - NSAID hypersensitivity in twins.

PMID- 25376172
TI  - A man walks into an ED....

PMID- 25376173
TI  - Uterine mast cell tumor: a clinical and cytohistopathological study.
AB  - BACKGROUND: Mast cells are one of the characteristic factors in angiogenesis,
      growth, and metastatic spread of tumors. Further studies are suggested to
      determine the type of these cells which might be useful in the assessment of
      biological nature of the tumor and its future treatment modality. Few studies
      have evaluated mast cell infiltration in visceral tumors, especially uterine
      tumors. CASE PRESENTATION: In this study, age, sex, death rate, and histologic
      patterns were in agreement with those of previous reports on canine mast cell
      tumors. Cytopathology assays are widely used to prognosticate canine uterine mast
      cell tumors (MCT). There is limited information about these prognostic assays
      used on MCT that arise in the uterine. The anisocytosis and anisocytosis and
      giant cells were present in the tumor. Furthermore, the tumor had nuclear atypia
      with scattered multinucleated cells and prominent nucleoli and tumor were
      classified as poorly granulated. Under microscopic examination, we observed
      diffuse infiltration and proliferation of tumor cells from the uterine different
      area and the infiltrative characteristics and distribution patterns of neoplastic
      cells were observed. This tumor consisted of sheets and cords of uniform round
      cells with discrete cytoplasmic margins. Microscopically, the neoplastic masses
      were poorly-demarcated and lacked capsules and tumor cell usually showed a
      distinct cell boundary. Nevertheless, the neoplastic cells were located between
      collagen bundles forming small clusters and sheets and had large, centrally
      located, round to ovoid nuclei. In addition, eosinophils were scattered among the
      mast cells at the periphery of the masses. The presence of eosinophils and the
      observation, at high magnification, of cells with cytoplasmic metachromatic
      granules. CONCLUSION: Based on these findings, a diagnosis of poorly
      differentiated mast cell tumor was made and data histologic grading was available
      for tumor. Neoplasm was poorly differentiated or gradeIII.

PMID- 25376175
TI  - The evolution of Momordica cyclic peptides.
AB  - Cyclic proteins have evolved for millions of years across all kingdoms of life to
      confer structural stability over their acyclic counterparts while maintaining
      intrinsic functional properties. Here, we show that cyclic miniproteins (or
      peptides) from Momordica (Cucurbitaceae) seeds evolved in species that diverged
      from an African ancestor around 19 Ma. The ability to achieve head-to-tail
      cyclization of Momordica cyclic peptides appears to have been acquired through a
      series of mutations in their acyclic precursor coding sequences following recent
      and independent gene expansion event(s). Evolutionary analysis of Momordica
      cyclic peptides reveals sites that are under selection, highlighting residues
      that are presumably constrained for maintaining their function as potent trypsin
      inhibitors. Molecular dynamics of Momordica cyclic peptides in complex with
      trypsin reveals site-specific residues involved in target binding. In a broader
      context, this study provides a basis for selecting Momordica species to further
      investigate the biosynthesis of the cyclic peptides and for constructing
      libraries that may be screened against evolutionarily related serine proteases
      implicated in human diseases. 

PMID- 25376176
TI  - Ectopic thyroid tissue in the head and neck: a case series.
AB  - BACKGROUND: Through a review of three cases, the etiopathogenetic, clinical
      diagnostic, and therapeutic aspects of ectopic thyroid tissue are herein
      discussed to highlight the main presentations of this polymorphous disease. CASE
      PRESENTATIONS: The first case involved an ectopic thyroid gland in the lingual
      area in a 45-year-old Caucasian woman who presented with dysphagia and midline
      swelling at the base of the tongue. The second case involved a 22-year-old
      Caucasian woman with a submandibular mass comprising ectopic thyroid tissue. The
      third case involved a 33-year-old Caucasian man with a typical thyroglossal duct
      cyst characterized by the presence of thyroid tissue upon histological analysis.
      CONCLUSION: Surgery seems to be the most appropriate treatment for patients with
      ectopic thyroid tissue showing clinical signs of upper airway obstruction or when
      the lesion shows signs of infection or malignant degeneration. When a site of
      ectopic thyroid tissue is the only such site in the body, removal of this tissue
      will usually lead to hypothyroidism that requires medical thyroid hormone
      replacement.

PMID- 25376177
TI  - Prophylactic intracameral antibiotic use during cataract surgery: response.

PMID- 25376178
TI  - Early diagnosis of celiac disease in IgA deficient children: contribution of a
      point-of-care test.
AB  - BACKGROUND: The serological diagnosis of celiac disease (CD) often relies on the
      presence of anti-tissue transglutaminase (tTG) IgA autoantibodies. Patients
      suffering from selective IgA deficiency (IgAD) are often not aware of their IgA
      deficiency and are tested as CD negative, delaying considerably the diagnosis.
      The detection of IgG against deamidated gliadin peptides (DGP) has high
      specificity and better sensitivity than IgG anti-tTG. A multi-analytic lateral
      flow immunochromatographic assay (CD-LFIA) based on the detection of IgA and IgG
      anti-DGP and total IgA was shown to have a good diagnostic accuracy for CD. The
      aim of this study was to evaluate the clinical accuracy of its use in children
      suffering from IgAD. METHODS: 45 IgAD children ranging from 1.1 to 17.4 years and
      suspected of CD or having high CD risk factors were referred from outpatient
      clinics located in the area of Rhone-Alpes (France) to the Hospices Civils de
      Lyon, Paediatric Hospital-Gastroenterology-Hepatology- Nutrition Department for
      further CD investigations. The CD investigations, including the sample
      collection, were performed within the Paediatric Hospital-Gastroenterology
      Hepatology- Nutrition Department, and the serological testing was performed at
      the Lyon-Sud Hospital-Immunology Laboratory. The diagnosis of CD was based on IgG
      anti-tTG serology, biopsy results and patient follow-up. The serum samples were
      retrospectively tested on the CD-LFIA test. RESULTS: A total of eight (8)
      patients were diagnosed as new CD. All were correctly identified by the CD-LFIA.
      The test yielded four (4) false positive results. Two patients with positive IgG
      anti-tTG were negative on CD-LFIA, but were classified as CD negative based on
      biopsy results and patient follow-up. The remaining 33 patients were found
      negative by both methods. The specificity and sensitivity of CD-LFIA was of 89.2%
      [74.6-97.0] and of 100% [63.1-100] respectively. The negative predictive value
      (NPV) was of 100% [89.4-100], and the Likelihood Ratio for Negative Test (LR-)
      was of 0 [0.0-0.91]. CONCLUSIONS: CD-LFIA is a useful, non-invasive and rapid
      tool to rule out CD in primary care paediatric patients having CD-related
      symptoms and IgAD. Patients having a positive CD-LFIA result could be then
      readily directed to secondary care setting for further evaluation by standard
      serology and biopsy.

PMID- 25376179
TI  - Is the systemic microvascular endothelial glycocalyx in peritoneal dialysis
      patients related to peritoneal transport?
AB  - BACKGROUND/AIMS: The capillary wall coated by the endothelial glycocalyx is the
      main transport barrier during peritoneal dialysis (PD). Here, we investigated the
      relationships between measurements of the systemic endothelial glycocalyx and
      peritoneal transport in PD patients. METHODS: We performed sidestream darkfield
      (SDF) imaging of the sublingual microvasculature in 15 patients, measured the
      perfused boundary region (PBR), which includes the permeable part of the
      glycocalyx, and calculated the estimated blood vessel density (EBVD). All
      patients underwent a peritoneal permeability analysis. RESULTS: No relationships
      were present between the imaging and peritoneal transport parameters, neither in
      the group as a whole nor in fast transporters. In patients with nonfast
      peritoneal transport status, PBR had a negative relationship with EBVD and small
      solute transport, and a positive one with net ultrafiltration (NUF). The EBVD
      showed a positive correlation with glucose absorption and a negative one with
      NUF. We found no relationships with the peritoneal transport of albumin.
      CONCLUSIONS: No relationships are present between the systemic endothelial
      glycocalyx, which was assessed by SDF, and peritoneal transport. In nonfast
      transporters, a reduction in blood vessel density caused by endothelial
      glycocalyx alterations or a thicker permeable phase of the glycocalyx delaying
      the access of small solutes to the small pores may be important. .

PMID- 25376180
TI  - Antitumor effect of photodynamic therapy with a novel targeted photosensitizer on
      cervical carcinoma.
AB  - The antitumor effect of photodynamic therapy (PDT) mediated by a novel
      photosensitizer I (Ps I; {gamma-[N-poly(ethyleneglycol)]folic acid}-5,10,15
      tris(3-hydroxyphenyl)-20-(4-carboxyphenyl)chlorin), in which chlorin was used as
      a photoactive unit, folic acid as a tumor-targeting warhead, and polyethylene
      glycol as a linker, on cervical carcinoma was studied in vitro and in vivo. Ps I
      exhibited a considerably higher cellular uptake by HeLa cells than folic acid
      free analogue Ps A (tert-butyl N-poly(ethyleneglycol)ethylcarbamate-5,10,15
      tris(3-hydroxyphenyl)-20-(4-carboxyphenyl)chlorin), and the cellular uptake by
      HeLa cells of Ps I could be competitively inhibited by excess folic acid.
      Moreover, at different time points after the intravenous (i.v.) injection of Ps I
      and A, Ps I produced a >2-fold higher tumor to normal tissue ratio in tumor
      bearing nude mice as compared to Ps A. MTT assay indicated that the HeLa cell
      proliferation inhibition ratio was increased 34% after Ps I-PDT compared with Ps
      A-PDT with a photosensitizer concentration of 15.2 umol/l. Administration of Ps I
      (7 mg/kg, i.v.) followed by light exposure (80 J/cm2) markedly suppressed the
      growth of xenograft tumors, and the tumor volume was 10-fold smaller than that of
      the control group. Tumor growth inhibition in vitro and in vivo had an obvious
      dependency on the Ps I concentration and irradiation dose. The mode of cell death
      post-Ps I-PDT was analyzed by flow cytometry, confocal laser scanning microscopy,
      and electron microscope, and the results suggested that apoptosis was the primary
      mode of HeLa cell death induced by Ps I-PDT. The results also demonstrated that
      tumor targeting of Ps I was clearly improved because of the endocytosis mediated
      by the folate receptor. As a result, Ps I-PDT exhibited higher antitumor activity
      than Ps A-PDT and has potential as an alternative treatment modality for cervical
      cancer.

PMID- 25376181
TI  - Progressive multifocal leukoencephalopathy in patients with a hematological
      malignancy: review of therapeutic options.
AB  - In the context of 2 patients with hematological malignancy who developed
      progressive multifocal leukoencephalopathy (PML), we review the current
      therapeutic options for this serious complication. Both patients had lymphoma and
      had been pretreated with the antibody rituximab. Diagnosis of PML was obtained
      upon the detection of the JC virus. The outcome was fatal in both cases. So far,
      no standard therapeutic approach for JC virus infection has been established in
      HIV-negative patients with hematological malignancies and the outcome is usually
      fatal. Serotonin receptor antagonists might have a beneficial effect by blocking
      the virus from entering the cells. Although hopes for the efficacy of mefloquine
      were disappointed by the results of 1 study, several case reports describe
      improvements in neurological impairment when this drug is administered. Taking
      the desperate situation of this patient group into consideration, the combination
      of mirtazapine and mefloquine might be worthy of an attempt.

PMID- 25376184
TI  - Development of a dietary-induced metabolic syndrome model using miniature pigs
      involvement of AMPK and SIRT1.
AB  - BACKGROUND: During the progression of the metabolic syndrome (MetS),
      cardiovascular diseases (CVD) appear clinically in many individuals and cause
      death. As a result, it is essential to set up an optimal animal model to study
      the mechanism of MetS leading to CVD. SIRT1 and AMPK are the master regulators of
      lipid and carbohydrate metabolism. The objective of this study was to establish a
      miniature pig model of Western diet-induced MetS and investigate the role of
      SIRT1/AMPK during MetS development. MATERIALS AND METHODS: Five-month-old Lee
      Sung (LS) and Lanyu (LY) minipigs were each randomly assigned to two groups:
      control diet (C) and Western diet (W), in a 6-month experimental period. RESULTS:
      Western diet caused obesity in both minipig models. Compared with the CLS pigs,
      WLS pigs exhibited hypercholesterolaemia. However, WLY pigs maintained a similar
      plasma lipid profile to the CLY pigs. Western diet caused a lower antioxidant
      capacity in the liver of both pig models. WLS pigs had higher triglyceride
      accumulation in the liver than CLS pigs, whereas WLY and CLY pigs had similar
      hepatic triglyceride accumulation. Compared with CLS pigs, WLS pigs had a lower
      hepatic SIRT1 expression, whereas WLY pigs had a higher expression of AMPK, FOXO1
      and SIRT1 than CLY pigs. CONCLUSION: Long-term feeding of the Western diet to Lee
      Sung miniature pigs not only caused obesity but also induced MetS and fatty
      liver, whereas Western diet induced obesity in Lanyu pigs without metabolic
      dysfunctions. SIRT1/AMPK and their downstream pathways might be one of the
      possible regulators for pathological obesity in Lee-Sung pigs.

PMID- 25376185
TI  - Immunocytochemical staining for stratifin and OCIAD2 in bronchial washing
      specimens increases sensitivity for diagnosis of lung cancer.
AB  - OBJECTIVE: Brushing or washing cytology taken at bronchoscopy is a standard
      diagnostic procedure for lung cancer. The present study evaluated the sensitivity
      of immunocytochemical diagnosis of lung cancer using bronchial washing materials.
      METHODS: We collected bronchial washing samples taken at bronchoscopy between
      July 2012 and July 2013 at Tsukuba University Hospital and studied 106 cases that
      were finally diagnosed as lung cancer. We collected exfoliated cells using a thin
      layer advanced cytology assay system (TACAS(TM)) and performed cytological
      diagnosis using Papanicolaou staining. As controls, we randomly selected 30
      tumour-negative cases from among samples collected during the same period. Using
      these materials, we also examined the expression of stratifin (14-3-3 sigma) (n =
      92) and OCIAD2 ovarian immunoreactive antigen domain 2) (n = 106) by
      immunocytochemistry, as these are considered to be broad spectrum immune markers
      for lung adenocarcinoma including early invasive lung adenocarcinoma. RESULTS:
      Using Papanicolaou staining, 52 out of 106 lung cancers (49.1%) were diagnosed as
      positive. However, positivity was increased to 63.0% by immunocytochemistry using
      anti-stratifin or anti-OCIAD2 antibodies. Biopsies were taken in 103/106 cases
      and cancer was diagnosed in 60/103, (58.3%). The sensitivity of stratifin or
      OCIAD2 was significantly higher than that of Papanicolaou staining (P = 0.027),
      but immunocytochemistry detected false-positive cells in 3/30 cases (10%) for
      stratifin and 2/30 cases (7%) for OCIAD2. CONCLUSION: Immunocytochemical staining
      for stratifin and OCIAD2 improved diagnostic sensitivity for lung cancers but
      diagnostic specificity was lower than that for cytology alone. The immunostains
      carried up to a 10% risk of a false-positive result and therefore positive
      staining must be confirmed by morphological evidence of malignancy.

PMID- 25376186
TI  - Monitoring phospholipase A2 activity with Gd-encapsulated phospholipid liposomes.
AB  - To date, numerous analytical methods have been developed to monitor phospholipase
      A2 (PLA2) activity. However, many of these methods require the use of unnatural
      PLA2 substrates that may alter enzyme kinetics, and probes that cannot be
      extended to applications in more complex environments. It would be desirable to
      develop a versatile assay that monitors PLA2 activity based on interactions with
      natural phospholipids in complex biological samples. Here, we developed an
      activatable T1 magnetic resonance (MR) imaging contrast agent to monitor PLA2
      activity. Specifically, the clinically approved gadolinium (Gd)-based MR contrast
      agent, gadoteridol, was encapsulated within nanometer-sized phospholipid
      liposomes. The encapsulated Gd exhibited a low T1-weighted signal, due to low
      membrane permeability. However, when the phospholipids within the liposomal
      membrane were hydrolyzed by PLA2, encapsulated Gd was released into bulk
      solution, resulting in a measureable change in the T1-relaxation time. These
      activatable MR contrast agents can potentially be used as nanosensors for
      monitoring of PLA2 activity in biological samples with minimal sample
      preparation. 

PMID- 25376189
TI  - Topical anesthesia or oral dextrose for the relief of pain in screening for
      retinopathy of prematurity: a randomized controlled double-blinded trial.
AB  - OBJECTIVE: Compare efficacy of 0.5% proparacaine eye drops and oral 25% dextrose
      in reducing pain during screening for retinopathy of prematurity (ROP). PATIENTS
      AND METHODS: Double-blinded randomized controlled trial. Twenty eligible babies
      were randomized. Group I received 0.5% proparacaine eye drops at first ROP
      screening, while Group II received 25% dextrose orally. At second examination,
      babies received no intervention. Pain was assessed using Premature Infant Pain
      Profile (PIPP) score. RESULTS: The mean ( +/- SD) PIPP during procedure in Group
      I were 15.5 +/- 2.06 and 14 +/- 2.4 at first and second screening (p = 0.259).
      The mean ( +/- SD) PIPP in Group II were 14.2 +/- 1. 8 and 14.9 +/- 2.5 at the
      first and second screening (p = 0.428). Differences were not statistically
      significant. The PIPP scores of Group I and Group II at the first screening were
      also not significantly different (p = 0.165). CONCLUSION: ROP screening causes
      moderate to severe pain and neither proparacaine nor dextrose is an effective
      analgesic.

PMID- 25376190
TI  - Caregivers' understanding of pediatric medication in central Malawi.
AB  - OBJECTIVE: To investigate caregivers' understanding of prescriptions of
      antibiotics and antimalarials for children in Malawi. METHOD: A cross-sectional
      study using interviews with 513 caregivers was undertaken in three different
      medical settings in two districts in Malawi for their understanding of medication
      defined as comprehension of dosage, frequency and duration immediately after
      receiving medicine, and its association with their sociodemographic
      characteristics. RESULTS: Nearly half (49%) of the caregivers understood
      medication on the day of prescription. Understanding varied by type of drug.
      Sixty-five percent understood medication for antimalarials, LA (lumefantrine and
      artemether), while only 38% understood medication for amoxicillin syrup.
      Multivariate analysis showed that caregivers with higher education and older
      children had greater understanding. CONCLUSIONS: Caregivers' understanding of
      pediatric medication was differentially related to kinds and types of medicine as
      well as their education level. The instruction to caregivers on how to administer
      medication should be evaluated especially when they are less educated.

PMID- 25376188
TI  - Left ventricular mass and the risk of sudden cardiac death: a population-based
      study.
AB  - BACKGROUND: Left ventricular (LV) mass ascertained using echocardiography may
      enhance risk stratification for sudden cardiac death. The objective of this study
      was to assess the association between left ventricular mass and the risk of
      sudden cardiac death in a population-based cohort and determine its incremental
      value beyond conventional risk predictors. METHODS AND RESULTS: Assessment of LV
      mass was based on echocardiography in a sample of 905 middle-aged men
      representative of the general population (aged 42 to 61 years). During the follow
      up period of 20 years, there were a total of 63 sudden cardiac deaths. In a
      comparison of the top versus the bottom quartile of LV mass adjusted by body
      surface area (>120 versus <89 g/m(2)), the multivariable adjusted hazard ratio
      was 2.57 (95% CI 1.24 to 5.31, P=0.010). Further adjustment for LV function only
      modestly attenuated the risk of sudden cardiac death among men with LV mass of
      >120 g/m(2) (hazard ratio 2.29, 95% CI 1.10 to 4.74, P=0.026). Addition of LV
      mass adjusted by body surface area to a conventional risk factor model for sudden
      cardiac death improved the integrated discrimination index by 0.033 (95% CI 0.009
      to 0.057, P=0.007) and the category-free net reclassification index by 0.501 (95%
      CI 0.092 to 0.911, P=0.016). CONCLUSIONS: Indexed LV mass by body surface area is
      an independent predictor of sudden cardiac death and may help improve the risk
      prediction of sudden cardiac death beyond conventional cardiovascular risk
      factors.

PMID- 25376191
TI  - Growth and change in attention problems, disruptive behavior, and achievement
      from kindergarten to fifth grade.
AB  - Despite widespread interest in children's adjustment problems, existing research
      does not provide conclusive evidence regarding the direction of the associations
      of achievement with classroom attention problems and disruptive behavior over the
      course of elementary school. Using a nationally representative sample of 16,260
      kindergarteners, this study examined the temporal sequence of achievement,
      classroom attention problems, and disruptive behavior, focusing on how changes in
      skills and problems unfold across key periods between kindergarten and fifth
      grade. Results indicate that improvements in attention during the earliest years
      of schooling predict achievement gains through third grade. However, changes in
      disruptive behavior do not predict subsequent changes in achievement. Evidence
      linking changes in achievement to changes in classroom attention problems and
      disruptive behavior was less consistent. These findings point to the need to
      develop and examine early interventions that can improve attention skills as a
      mechanism for improving children's academic trajectories in elementary school. 

PMID- 25376187
TI  - Tenascin-C aggravates autoimmune myocarditis via dendritic cell activation and
      Th17 cell differentiation.
AB  - BACKGROUND: Tenascin-C (TN-C), an extracellular matrix glycoprotein, appears at
      several important steps of cardiac development in the embryo, but is sparse in
      the normal adult heart. TN-C re-expresses under pathological conditions including
      myocarditis, and is closely associated with tissue injury and inflammation in
      both experimental and clinical settings. However, the pathophysiological role of
      TN-C in the development of myocarditis is not clear. We examined how TN-C affects
      the initiation of experimental autoimmune myocarditis, immunologically. METHODS
      AND RESULTS: A model of experimental autoimmune myocarditis was established in
      BALB/c mice by immunization with murine alpha-myosin heavy chains. We found that
      TN-C knockout mice were protected from severe myocarditis compared to wild-type
      mice. TN-C induced synthesis of proinflammatory cytokines, including interleukin
      (IL)-6, in dendritic cells via activation of a Toll-like receptor 4, which led to
      T-helper (Th)17 cell differentiation and exacerbated the myocardial inflammation.
      In the transfer experiment, dendritic cells loaded with cardiac myosin peptide
      acquired the functional capacity to induce myocarditis when stimulated with TN-C;
      however, TN-C-stimulated dendritic cells generated from Toll-like receptor 4
      knockout mice did not induce myocarditis in recipients. CONCLUSIONS: Our results
      demonstrated that TN-C aggravates autoimmune myocarditis by driving the dendritic
      cell activation and Th17 differentiation via Toll-like receptor 4. The blockade
      of Toll-like receptor 4-mediated signaling to inhibit the proinflammatory effects
      of TN-C could be a promising therapeutic strategy against autoimmune myocarditis.

PMID- 25376192
TI  - Conceptual processing of distractors by older but not younger adults.
AB  - Evidence from perceptually based implicit memory tasks demonstrates greater
      priming from distracting information among older compared with younger adults. We
      examined whether older adults also show greater conceptually based implicit
      priming from distracting information. We measured priming using a general
      knowledge test that was preceded by an incidental-encoding task (a color-naming
      Stroop task in one experiment and a 1-back task involving pictures with
      irrelevant words superimposed in a second experiment). Younger adults showed no
      priming from the distracting information in either experiment, whereas older
      adults showed reliable priming in both experiments. Thus, unlike young adults,
      older adults process irrelevant information conceptually and then can use that
      information to boost their performance on a subsequent task. 

PMID- 25376193
TI  - Prevalence, Patient Characteristics, and Pharmacological Treatment of Children,
      Adolescents, and Adults Diagnosed With ADHD in Sweden.
AB  - OBJECTIVE: The objective of this study was to describe the epidemiology of
      diagnosed ADHD and the pharmacological treatment of patients with ADHD in Sweden.
      Specifically, this study estimates the prevalence of patients with a newly
      registered diagnosis of ADHD over a 5-year period, and the prevalence of all
      patients with a registered ADHD diagnoses over a 6-year period in Sweden. METHOD:
      Two population-based registries were used as data sources for this study; the
      National Patient Register (NPR) and the Prescribed Drug Register (PDR). The
      international Classification of Diseases 10th Revison (ICD-10) was used to
      identify patients with ADHD. RESULTS: The annual prevalence of ADHD in the
      general population of Sweden was found to be 1.1 per 1,000 persons in the year
      2006 increasing to 4.8 per 1,000 persons in 2011. The corresponding prevalence
      for newly diagnosed patients increased from 0.6 per 1,000 persons in 2007 to 1.3
      per 1,000 persons in 2011. The majority of diagnosed patients received
      pharmacological treatment, with methylphenidate being the most common dispensed
      drug. Comorbidities in the autism spectrum were most common for younger patients,
      while substance abuse, anxiety, and personality disorder were the most common
      comorbidities in older patients. CONCLUSION: From 2006 to 2011, the number of
      patients diagnosed with ADHD has increased in Sweden over all ages. The majority
      of patients diagnosed with ADHD in Sweden received a pharmacological treatment
      regardless of age. An ADHD diagnosis was often accompanied with psychiatric
      comorbidity.

PMID- 25376194
TI  - Effect on Primary Sleep Disorders When Children With ADHD Are Administered
      Guanfacine Extended Release.
AB  - OBJECTIVE: To evaluate children with ADHD and sleep problems with polysomnography
      (PSG) after guanfacine extended-release (GXR) administration. METHOD: Double
      blind, randomized, placebo-controlled study was terminated early due to treatment
      emergent concerns after enrolling 29 children aged 6 to 12 years. After >4 weeks
      dose adjustment and >1 week dose stabilization, 11 children received GXR and 16
      controls underwent analyses with PSG. RESULTS: Although GXR improved ADHD
      symptoms, the primary outcome variable, total sleep time, was shorter in contrast
      to placebo (-57.32, SD = 89.17 vs. +31.32, SD = 59.54 min, p = .005). Increased
      time awake after sleep onset per hour of sleep was the primary factor for the
      reduction. Although rapid eye movement (REM), non-REM, and N3/slow wave sleep
      times were reduced, these were proportional to the overall sleep reduction.
      Sedation was common with GXR (73% vs. 6%). CONCLUSION: Morning-administered GXR
      resulted in decreased sleep and may contribute to sedation.

PMID- 25376195
TI  - Indoxyl sulfate induces IL-6 expression in vascular endothelial and smooth muscle
      cells through OAT3-mediated uptake and activation of AhR/NF-kappaB pathway.
AB  - BACKGROUND/AIMS: Interleukin-6 (IL-6) is one of the inflammation biomarkers with
      highest predictive value for outcome in chronic kidney disease (CKD) patients.
      The present study aimed to determine the effects of indoxyl sulfate (IS) on IL-6
      expression in vascular cells. METHODS: IS was administered to normo- and
      hypertensive rats. Human umbilical vein endothelial cells (HUVECs) and human
      aortic smooth muscle cells (HASMCs) were incubated with or without IS. RESULTS:
      Immunohistochemistry revealed that IS-administered rats showed increased
      expression of IL-6 in the aortic tissues. IS increased IL-6 expression in HUVECs
      and HASMCs in a time- and dose-dependent manner. Knockdown of organic anion
      transporter 3 (OAT3) using small interfering RNA (siRNA) inhibited IS-induced
      expression of IL-6 in HUVECs and HASMCs. IS induced activation of aryl
      hydrocarbon receptor (AhR) and nuclear factor-kappaB (NF-kappaB) subunit p65 in
      HUVECs and HASMCs. Both AhR siRNA and p65 siRNA inhibited IS-induced expression
      of IL-6. AhR siRNA inhibited IS-induced phosphorylation and nuclear translocation
      of p65 without change in total p65 level. However, p65 siRNA did not inhibit IS
      induced nuclear translocation of AhR. Thus, AhR is responsible for IS-induced p65
      signaling transduction. CONCLUSION: IS induces IL-6 expression in vascular
      endothelial and smooth muscle cells through OAT3/AhR/NF-kappaB pathway.

PMID- 25376196
TI  - Supine or sitting plasma metanephrine screening? A unifying solution for patients
      and doctors.

PMID- 25376197
TI  - When and how to use steatosis biomarkers?

PMID- 25376198
TI  - Baclofen and transient lower oesophageal sphincter relaxations - the band plays
      on.

PMID- 25376199
TI  - Editorial: baclofen and transient lower oesophageal sphincter relaxations - the
      band plays on - authors' reply.

PMID- 25376200
TI  - Sprue-like enteropathy associated with olmesartan - broadening the differential
      diagnosis of enteropathy.

PMID- 25376201
TI  - Using pictures to improve communication between doctor and patient in functional
      gastrointestinal disorders.

PMID- 25376202
TI  - Oral B12 replacement in Crohn's disease - is B12 by injection obsolete?

PMID- 25376203
TI  - Using pictures to improve communication between doctor and patient in functional
      gastrointestinal disorders - authors' reply.

PMID- 25376204
TI  - PPI vs. teprenone in preventing recurrence of ulcers during low-dose aspirin -
      authors' reply.

PMID- 25376205
TI  - PPI vs. teprenone in preventing recurrence of ulcers during low-dose aspirin.

PMID- 25376206
TI  - Hepatocellular carcinoma in thalassaemia - emerging issues and challenges for
      liver transplant.

PMID- 25376207
TI  - Fatal Scopulariopsis infection in a lung transplant recipient: lessons of organ
      procurement.
AB  - Seventeen days after double lung transplantation, a 56-year-old patient with
      idiopathic pulmonary fibrosis developed respiratory distress. Imaging revealed
      bilateral pulmonary infiltrates with pleural effusions and physical examination
      demonstrated sternal instability. Broad-spectrum antibacterial and antifungal
      therapy was initiated and bilateral thoracotomy tubes were placed. Both right and
      left pleural cultures grew a mold subsequently identified as Scopulariopsis
      brumptii. The patient underwent pleural irrigation and sternal debridement three
      times but pleural and wound cultures continued to grow S. brumptii. Despite
      treatment with five antifungal agents, the patient succumbed to his illness 67
      days after transplantation. Autopsy confirmed the presence of markedly invasive
      fungal disease and pleural rind formation. The patient's organ donor had received
      bilateral thoracostomy tubes during resuscitation in a wilderness location. There
      were no visible pleural abnormalities at the time of transplantation. However,
      the patient's clinical course and the location of the infection, in addition to
      the lack of similar infection in other organ recipients, strongly suggest that
      Scopulariopsis was introduced into the pleural space during prehospital placement
      of thoracostomy tubes. This case of lethal infection transmitted through
      transplantation highlights the unique risk of using organs from donors who are
      resuscitated in an outdoor location. 

PMID- 25376208
TI  - B cell lymphoma with lung involvement: what is it about?
AB  - Primary lymphoma of the lung or pleural is a very rare condition. Due to the
      outdated literature data, the approximate occurrence of primary and secondary
      lung and/or pleural involvement according to the most common B cell lymphoma
      entities is unknown. To answer this open question in Austria, we screened the
      Tyrolean registry for B cell non-Hodgkin's lymphomas regarding primary and
      secondary lung involvement. Of 854 patients affected by B cell lymphoma, 7.5% had
      lung/pleural disease. This organ was the primary site in only 0.7%, while a
      secondary involvement was registered in 6.8%. Most of them were affected by
      diffuse large B cell lymphoma (DLBCL; 29/368, 8%) followed by follicular lymphoma
      (7/188, 4%), mantle cell lymphoma (7/57, 12%), mucosa-associated tissue lymphoma
      (10/37, 27%), posttransplant lymphoproliferative disease (6/24, 25%), Burkitt
      lymphoma (3/19, 16%), other lymphomas (1/32, 3%) and Richter transformation
      (1/11, 9%). Moreover, primary lung/pleural lymphoma is one of the rarest
      neoplasias affecting the lung, accounting for only 0.4% of cases. Lung/pleural
      involvement is a very rare condition among B cell lymphomas since it mainly
      occurs in the setting of a generalized disease. A large majority of patients with
      secondary organ involvement are affected by DLBCL and have similar clinical
      features at diagnosis to others with advanced-stage disease.

PMID- 25376209
TI  - N-acetyltransferase 2 gene polymorphism as a biomarker for susceptibility to
      bladder cancer in Bangladeshi population.
AB  - AIM: To investigate the association between the three most common single
      nucleotide polymorphisms of the N-acetyltransferase 2 gene together with
      cigarette smoking and the risk of developing bladder cancer and its
      aggressiveness. METHODS: A case-control study on 102 bladder cancer patients and
      140 control subjects was conducted. The genomic DNA was extracted from peripheral
      white blood cells and N-acetyltransferase 2 alleles were differentiated by
      polymerase chain reaction-based restriction fragment length polymorphism methods.
      RESULTS: Bladder cancer risk was estimated as odds ratio and 95% confidence
      interval using binary logistic regression models adjusting for age and gender.
      Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer
      risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers
      with slow genotypes were found to have a sixfold increased risk to develop
      bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients
      with slow acetylating genotypes were more prone to develop high-grade (odds
      ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds
      ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor. CONCLUSION: N
      acetyltransferase 2 slow genotype together with tobacco smoking increases bladder
      cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely
      to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype
      is an important genetic determinant for bladder cancer in Bangladesh population.

PMID- 25376210
TI  - Academic identity formation and motivation among ethnic minority adolescents: the
      role of the "self" between internal and external perceptions of identity.
AB  - Identity is often studied as a motivational construct within research on
      adolescent development and education. However, differential dimensions of
      identity, as a set of internal values versus external perceptions of social
      belonging, may relate to motivation in distinct ways. Utilizing a sample of 600
      African American and Latino adolescents (43% female; mean age = 13.9), the
      present study examines whether self-regulated learning (SRL) mediates two
      distinct dimensions of academic identity (i.e., value and belonging) and mastery
      orientation. This study also examines whether self-efficacy moderates the
      mediating role of SRL between identity and mastery. Results show evidence for
      moderated mediation between SRL and academic self-efficacy. Self-regulated
      learning played its strongest mediating role between belonging and mastery and
      for low-efficacy students specifically. 

PMID- 25376211
TI  - Is reducing dietary sodium controversial? Is it the conduct of studies with
      flawed research methods that is controversial? A perspective from the World
      Hypertension League Executive Committee.

PMID- 25376212
TI  - Dr Gianvincenzo Barba.

PMID- 25376213
TI  - Usual energy and macronutrient intakes in 2-9-year-old European children.
AB  - OBJECTIVE: Valid estimates of population intakes are essential for monitoring
      trends as well as for nutritional interventions, but such data are rare in young
      children. In particular, the problem of misreporting in dietary data is usually
      not accounted for. Therefore, this study aims to provide accurate estimates of
      intake distributions in European children. DESIGN: Cross-sectional setting-based
      multi-centre study. SUBJECTS: A total of 9560 children aged 2-9 years from eight
      European countries with at least one 24-h dietary recall (24-HDR). METHODS: The
      24-HDRs were classified in three reporting groups based on age- and sex-specific
      Goldberg cutoffs (underreports, plausible reports, overreports). Only plausible
      reports were considered in the final analysis (N=8611 children). The National
      Cancer Institute (NCI)-Method was applied to estimate population distributions of
      usual intakes correcting for the variance inflation in short-term dietary data.
      RESULTS: The prevalence of underreporting (9.5%) was higher compared with
      overreporting (3.4%). Exclusion of misreports resulted in a shift of the energy
      and absolute macronutrient intake distributions to the right, and further led to
      the exclusion of extreme values, that is, mean values and lower percentiles
      increased, whereas upper percentiles decreased. The distributions of relative
      macronutrient intakes (% energy intake from fat/carbohydrates/proteins) remained
      almost unchanged when excluding misreports. Application of the NCI-Method
      resulted in markedly narrower intake distributions compared with estimates based
      on single 24-HDRs. Mean percentages of usual energy intake from fat,
      carbohydrates and proteins were 32.2, 52.1 and 15.7%, respectively, suggesting
      the majority of European children are complying with common macronutrient intake
      recommendations. In contrast, total water intake (mean: 1216.7 ml per day) lay
      below the recommended value for >90% of the children. CONCLUSION: This study
      provides recent estimates of intake distributions of European children correcting
      for misreporting as well as for the daily variation in dietary data. These data
      may help to assess the adequacy of young children's diets in Europe.

PMID- 25376214
TI  - Dietary energy density in young children across Europe.
AB  - OBJECTIVES: To describe energy density (ED; kcal g(-1)) of dietary intake of
      European children. METHODS: From 16, 228 children who participated in the IDEFICS
      (Identification and prevention of Dietary- and lifestyle-induced health EFfects
      In Children and infantS) baseline examination, 8551 children with 24-h dietary
      recalls (24-HDR), with plausible reported energy intakes and complete covariate
      information were included in the present analysis. ED was calculated using two
      methods: (1) ED including solid foods (EDF) and (2) ED including solid foods and
      energy-containing beverages (EDF&B). Beverage energy was calculated in kcal per
      day. Dietary characteristics and body mass index (BMI) z-score of children aged 2
      to <6 years and 6 to <10 years were compared between children with an overall EDF
      below the <25th percentile, between the 25th and 75th percentile as well as above
      the >75th percentile. Standardised regression coefficients were estimated to
      assess the association between dietary characteristics, BMI z-score and ED of the
      diet. RESULTS: Children with low EDF and EDF&B diets consumed less energy but
      higher quantity of food and beverages than children with high EDF and EDF&B
      diets. Consumption of caloric beverages decreased with increasing EDF&B of the
      diet owing to the relatively low ED of the beverages, in relation to solid foods.
      Generally, children with low EDF and EDF&B diets showed healthier food choices
      than peers with higher EDF and EDF&B diets. In this sample, EDF and EDF&B were
      not associated with BMI z-score. CONCLUSION: Health promotion strategies should
      proclaim lower ED diets by means of foods with high water and low fat content and
      mainly fruit and vegetable components. Excluding caloric beverages from EDF
      calculation is a useful method to avoid misinterpretation of true exposure to a
      high energy dense diet. We recommend excluding caloric beverages from EDF
      calculation when investigating the effect of ED on a certain (health) outcome.

PMID- 25376215
TI  - Objectively measured physical activity in European children: the IDEFICS study.
AB  - OBJECTIVES: To provide sex- and age-specific percentile values for levels of
      physical activity (PA) and sedentary time of European children aged 2.0-10.9
      years from eight European countries (Sweden, Germany, Hungary, Italy, Cyprus,
      Spain, Belgium and Estonia). METHODS: Free-living PA and sedentary time were
      objectively assessed using ActiGraph GT1M or ActiTrainer activity monitors in all
      children who had at least 3 days' worth of valid accelerometer data, with at
      least 8 h of valid recording time each day. The General Additive Model for
      Location Scale and Shape was used for calculating percentile curves. RESULTS:
      Reference values for PA and sedentary time in the European children according to
      sex and age are displayed using smoothed percentile curves for 7684 children
      (3842 boys and 3842 girls). The figures show similar trends in boys and girls.
      The percentage of children complying with recommendations regarding moderate-to
      vigorous physical activity (MVPA) is also presented and varied considerably
      between sexes and country. For example, the percentage of study participants who
      were physically active (as assessed by MVPA) for 60 or more minutes per day
      ranged from 2.0% (Cyprus) to 14.7% (Sweden) in girls and from 9.5% (Italy) to
      34.1% (Belgium) in boys. CONCLUSION: This study provides the most up-to-date sex-
      and age-specific reference data on PA in young children in Europe. The percentage
      compliance to MVPA recommendations for these European children varied
      considerably between sexes and country and was generally low. These results may
      have important implications for public health policy and PA counselling.

PMID- 25376216
TI  - Adherence to the obesity-related lifestyle intervention targets in the IDEFICS
      study.
AB  - BACKGROUND/OBJECTIVES: To address behaviours associated with childhood obesity,
      certain target values are recommended that should be met to improve children's
      health. In the IDEFICS (Identification and prevention of Dietary- and lifestyle
      induced health Effects in Children and infantS) study such lifestyle
      recommendations were conveyed as six key messages. Here, we investigate the
      adherence of European children to these messages. METHODS: The IDEFICS
      intervention was based on the intervention mapping approach with the following
      six targets: increase water consumption (to replace sugar-containing beverages),
      increase fruit/vegetable consumption, reduce daily screen time, increase daily
      physical activity, improve the quality of family life and ensure adequate sleep
      duration. Internationally recommended target values were applied to determine the
      prevalence of children meeting these targets. RESULTS: In a cohort of 18,745
      children participating in the IDEFICS baseline survey or newly recruited during
      follow-up, data on the above lifestyle behaviours were collected for a varying
      number of 8302 to 17,212 children. Information on all six behaviours was
      available for 5140 children. Although 52.5% of the cohort was classified in the
      highest category of water consumption, only 8.8% met the target of an intake of
      fruits/vegetables five times a day. The prevalence of children adhering to the
      recommendation regarding total screen time-below 1 h for pre-school children and
      2 h for school children-was 51.1%. The recommended amount of at least 60 min of
      moderate-to-vigorous physical activity per day was fulfilled by 15.2%. Family
      life of the child measured by various indicators was considered as satisfactory
      in 22.8%. Nocturnal sleep duration of 11 (10) hours or more in pre-school
      (school) children was achieved by 37.9%. In general, children in northern
      countries and younger children showed better adherence to the recommendations.
      Only 1.1% of the children adhered to at least five of these recommendations.
      CONCLUSIONS: Current adherence of children to lifestyle recommendations to
      prevent childhood obesity is low where observed differences with respect to
      country, age and gender call for targeted intervention.

PMID- 25376218
TI  - C-reactive protein reference percentiles among pre-adolescent children in Europe
      based on the IDEFICS study population.
AB  - OBJECTIVES: C-reactive protein (CRP) is involved in a wide range of diseases. It
      is a powerful marker for inflammatory processes used for diagnostic and
      monitoring purposes. We aimed to establish reference values as data on the
      distribution of serum CRP levels in young European children are scarce. SUBJECTS:
      Reference values of high-sensitivity CRP concentrations were calculated for 9855
      children aged 2.0-10.9 years, stratified by age and sex. The children were
      recruited during the population-based European IDEFICS study (Identification and
      prevention of Dietary- and lifestyle-induced health Effects in Children and
      infantS) with 18 745 participants recruited from 2007 to 2010. RESULTS: In 44.1%
      of the children, CRP values were below or equal the detection limit of 0.2 mg/l.
      Median CRP concentrations showed a slight negative age trend in boys and girls,
      whereas serum CRP values were slightly higher in girls than in boys across all
      age groups. CONCLUSIONS: Our population-based reference values of CRP may guide
      paediatric practice as elevated values may require further investigation or
      treatment. Therefore, the presented reference values represent a basis for
      clinical evaluation and for future research on risk assessment of diseases
      associated with increased CRP levels among children.

PMID- 25376219
TI  - Percentiles of fasting serum insulin, glucose, HbA1c and HOMA-IR in pre-pubertal
      normal weight European children from the IDEFICS cohort.
AB  - OBJECTIVES: The aim of this study is to present age- and sex-specific reference
      values of insulin, glucose, glycosylated haemoglobin (HbA1c) and the homeostasis
      model assessment to quantify insulin resistance (HOMA-IR) for pre-pubertal
      children. METHODS: The reference population consists of 7074 normal weight 3- to
      10.9-year-old pre-pubertal children from eight European countries who
      participated in at least one wave of the IDEFICS ('identification and prevention
      of dietary- and lifestyle-induced health effects in children and infants')
      surveys (2007-2010) and for whom standardised laboratory measurements were
      obtained. Percentile curves of insulin (measured by an electrochemiluminescence
      immunoassay), glucose, HbA1c and HOMA-IR were calculated as a function of age
      stratified by sex using the general additive model for location scale and shape
      (GAMLSS) method. RESULTS: Levels of insulin, fasting glucose and HOMA-IR
      continuously show an increasing trend with age, whereas HbA1c shows an upward
      trend only beyond the age of 8 years. Insulin and HOMA-IR values are higher in
      girls of all age groups, whereas glucose values are slightly higher in boys.
      Median serum levels of insulin range from 17.4 and 13.2 pmol l(-1) in 3-<3.5-year
      old girls and boys, respectively, to 53.5 and 43.0 pmol l(-1) in 10.5-<11-year
      old girls and boys. Median values of glucose are 4.3 and 4.5 mmol l(-1) in the
      youngest age group and 49.3 and 50.6 mmol l(-1) in the oldest girls and boys. For
      HOMA-IR, median values range from 0.5 and 0.4 in 3-<3.5-year-old girls and boys
      to 1.7 and 1.4 in 10.5-<11-year-old girls and boys, respectively. CONCLUSIONS:
      Our study provides the first standardised reference values for an international
      European children's population and provides the, up to now, largest data set of
      healthy pre-pubertal children to model reference percentiles for markers of
      insulin resistance. Our cohort shows higher values of Hb1Ac as compared with a
      single Swedish study while our percentiles for the other glucose metabolic
      markers are in good accordance with previous studies.

PMID- 25376221
TI  - Physical fitness reference standards in European children: the IDEFICS study.
AB  - BACKGROUND/OBJECTIVES: A low fitness status during childhood and adolescence is
      associated with important health-related outcomes, such as increased future risk
      for obesity and cardiovascular diseases, impaired skeletal health, reduced
      quality of life and poor mental health. Fitness reference values for adolescents
      from different countries have been published, but there is a scarcity of
      reference values for pre-pubertal children in Europe, using harmonised measures
      of fitness in the literature. The IDEFICS study offers a good opportunity to
      establish normative values of a large set of fitness components from eight
      European countries using common and well-standardised methods in a large sample
      of children. Therefore, the aim of this study is to report sex- and age-specific
      fitness reference standards in European children. SUBJECTS/METHODS: Children
      (10,302) aged 6-10.9 years (50.7% girls) were examined. The test battery
      included: the flamingo balance test, back-saver sit-and-reach test (flexibility),
      handgrip strength test, standing long jump test (lower-limb explosive strength)
      and 40-m sprint test (speed). Moreover, cardiorespiratory fitness was assessed by
      a 20-m shuttle run test. Percentile curves for the 1st, 3rd, 10th, 25th, 50th,
      75th, 90th, 97th and 99th percentiles were calculated using the General Additive
      Model for Location Scale and Shape (GAMLSS). RESULTS: Our results show that boys
      performed better than girls in speed, lower- and upper-limb strength and
      cardiorespiratory fitness, and girls performed better in balance and flexibility.
      Older children performed better than younger children, except for
      cardiorespiratory fitness in boys and flexibility in girls. CONCLUSIONS: Our
      results provide for the first time sex- and age-specific physical fitness
      reference standards in European children aged 6-10.9 years.

PMID- 25376220
TI  - Metabolic syndrome in young children: definitions and results of the IDEFICS
      study.
AB  - OBJECTIVE: To estimate the prevalence of the metabolic syndrome (MetS) using
      reference standards obtained in European children and to develop a quantitative
      MetS score and describe its distribution in children. DESIGN AND METHODS:
      Population-based survey in eight European countries, including 18745 children 2.0
      to 10.9 years, recruited during a second survey. Anthropometry (weight, height
      and waist circumference), blood pressure and serum-fasting triglycerides, HDL
      cholesterol, glucose and insulin were measured. We applied three widely accepted
      definitions of the pediatric MetS and we suggest a new definition, to guide
      pediatricians in decisions about close monitoring or even intervention (values of
      at least three of the MetS components exceeding the 90th or 95th percentile,
      respectively). We used a z-score standardisation to calculate a continuous score
      combining the MetS components. RESULTS: Among the various definitions of MetS,
      the highest prevalence (5.5%) was obtained with our new definition requiring
      close observation (monitoring level). Our more conservative definition, requiring
      pediatric intervention gives a prevalence of 1.8%. In general, prevalences were
      higher in girls than in boys. The prevalence of metabolic syndrome is highest
      among obese children. All definitions classify a small percentage of thin or
      normal weight children as being affected. The metabolic syndrome score shows a
      positive trend with age, particularly regarding the upper percentiles of the
      score. CONCLUSIONS: According to different definitions of pediatric MetS, a non
      negligible proportion of mostly prepubertal children are classified as affected.
      We propose a new definition of MetS that should improve clinical guidance. The
      continuous score developed may also serve as a useful tool in pediatric obesity
      research. It has to be noted, however, that the proposed cutoffs are based on a
      statistical definition that does not yet allow to quantify the risk of subsequent
      disease.

PMID- 25376223
TI  - Prevalence of overweight and obesity in European children below the age of 10.
AB  - BACKGROUND: There is a lack of common surveillance systems providing comparable
      figures and temporal trends of the prevalence of overweight (OW), obesity and
      related risk factors among European preschool and school children. Comparability
      of available data is limited in terms of sampling design, methodological
      approaches and quality assurance. The IDEFICS (Identification and prevention of
      Dietary- and lifestyle-induced health Effects in Children and infantS) study
      provides one of the largest European data sets of young children based on state
      of-the-art methodology. OBJECTIVE: To assess the European distribution of weight
      status according to different classification systems based on body mass index
      (BMI) in children (2.0-9.9 years). To describe the prevalence of weight
      categories by region, sex, age and socioeconomic position. DESIGN: Between 2007
      and 2010, 18,745 children from eight European countries participated in an
      extensive, highly standardised protocol including, among other measures,
      anthropometric examinations and parental reports on socio-demographic
      characteristics. RESULTS: The combined prevalence of OW/obesity ranges from more
      than 40% in southern Europe to less than 10% in northern Europe. Overall, the
      prevalence of OW was higher in girls (21.1%) as compared with boys (18.6%). The
      prevalence of OW shows a negative gradient with social position, with some
      variation of the strength and consistency of this association across Europe.
      Overall, population groups with low income and/or lower education levels show the
      highest prevalence of obesity. The use of different reference systems to classify
      OW results in substantial differences in prevalence estimates and can even
      reverse the reported difference between boys and girls. CONCLUSIONS: There is a
      higher prevalence of obesity in populations from southern Europe and in
      population groups with lower education and income levels. Our data confirm the
      need to develop and reinforce European public health policies to prevent early
      obesity and to reduce these health inequalities and regional disparities.

PMID- 25376222
TI  - Reference values of bone stiffness index and C-terminal telopeptide in healthy
      European children.
AB  - BACKGROUND/OBJECTIVE: Quantitative ultrasound measurements and bone metabolic
      markers can help to monitor bone health and to detect impaired skeletal
      development. Population-based reference values for children may serve as a basis
      for preventive measures to reduce the risk of osteoporosis and osteoporotic
      fractures in later life. This is the first paper providing age-, sex- and height
      specific reference values for bone stiffness index (SI) and serum carboxy
      terminal cross-linking telopeptide of type I collagen (CTX) in healthy,
      apparently prepubertal children. SUBJECTS/METHODS: In the population-based
      IDEFICS baseline survey (2007-2008) and follow-up (2009-2010), 18,745 children
      from eight European countries were newly recruited. A total of 10,791 2-10.9-year
      old and 1646 3-8.9-year-old healthy children provided data on SI of the right and
      left calcaneus and serum CTX, respectively. Furthermore, height and weight were
      measured. Percentile curves were calculated using the General Additive Model for
      Location Scale and Shape (GAMLSS) to model the distribution of SI and CTX
      depending on multiple covariates while accounting for dispersion, skewness, and
      the kurtosis of this distribution. RESULTS: SI was negatively associated with age
      and height in children aged 2-5 years, whereas a positive association was
      observed in children aged 6-10 years. The dip in SI occurred at older age for
      higher SI percentiles and was observed earlier in taller children than in smaller
      children. The CTX reference curves showed a linear-positive association with age
      and height. No major sex differences were observed for the SI and CTX reference
      values. CONCLUSION: These reference data lay the ground to evaluate bone growth
      and metabolism in prepubertal children in epidemiological and clinical settings.
      They may also inform clinical practice to monitor skeletal development and to
      assess adverse drug reactions during medical treatments.

PMID- 25376225
TI  - Nursing Staff's Perception of Barriers in Providing End-of-Life Care to
      Terminally Ill Pediatric Patients in Southeast Iran.
AB  - OBJECTIVE: To determine pediatric nurses' perceptions of intensity, frequency
      occurrence, and magnitude score of selected barriers in providing pediatric end
      of-life (EOL) care. METHOD: A translated modified version of National Survey of
      critical care Nurses' s Regarding End-of-Life Care questionnaire was used to
      assess 151 nurses' perceptions of intensity and frequency occurrence of barriers
      in caring for dying children. RESULTS: The highest/lowest perceived barriers
      magnitude scores were "families not accepting poor child prognosis" (5.04) and
      "continuing to provide advanced treatment to dying child because of financial
      benefits to the hospital" (2.19). CONCLUSION: More high perceived barriers by
      nurses were family-related issues. One of the possible causes of such
      deficiencies was lack of palliative care (PC) education/PC units in Iran. Thus,
      developing EOL/PC education may enhance nurses' knowledge/skill to face EOL care
      challenges.

PMID- 25376226
TI  - An Evaluation of a Bereavement Program in a US Research Hospital.
AB  - The Bereavement Program at the National Institutes of Health (NIH) Clinical
      Center was established in 2005. The program makes contact with the next of kin on
      4 occasions postnotification of death. The objective of this analysis was to
      evaluate program effectiveness for those individuals who we successfully made
      contact with on all 4 occasions (N = 39). At 12 months postnotification, the
      majority viewed the NIH as a source of support (56%), and the frequency of
      positive emotional ratings increased (59%). There are limitations to this
      analysis, and biases may be present. In sum, this analysis serves as an example
      of a successful hospital-based bereavement program that enrolls patients who have
      been treated at the institution in any capacity who are also patients enrolled in
      institutional review board-approved research protocols. 

PMID- 25376224
TI  - Assessment and Management of Symptoms for Outpatients Newly Diagnosed With Lung
      Cancer.
AB  - RATIONALE: Little is known about symptom assessment around the time of lung
      cancer diagnosis. The purpose of this pilot study was to assess symptoms within 2
      months of diagnosis and the frequency with which clinicians addressed symptoms
      among a cohort of veterans (n = 20) newly diagnosed with lung cancer. We
      administered questionnaires and then reviewed medical records to identify symptom
      assessment and management provided by subspecialty clinics for 6 months following
      diagnosis. RESULTS: Half (50%) of the patients were diagnosed with early-stage
      non-small-cell lung cancer (NSCLC), stage I or II. At baseline, 45% patients
      rated their overall symptoms as severe. There were no significant differences in
      symptoms among patients with early- or late-stage NSCLC or small-cell lung
      cancer. Of the 212 clinic visits over 6 months, 70.2% occurred in oncology.
      Clinicians most frequently addressed pain although assessment differed by clinic.
      CONCLUSIONS: Veterans with newly diagnosed lung cancer report significant symptom
      burden. Despite ample opportunities to address patients' symptoms, variations in
      assessment exist among subspecialty services. Coordinated approaches to symptom
      assessment are likely needed among patients newly diagnosed with lung cancer.

PMID- 25376227
TI  - Two cases of atypical meningioma with pulmonary metastases: a comparative
      cytogenetic analysis of chromosomes 1p and 22 and a review of the literature.
AB  - We present two cases of atypical meningioma WHO grade II with a history of
      multiple local recurrences and late pulmonary metastases. Comparative cytogenetic
      analyses on 1p and 22q confirmed clonal origin of the primary intracranial
      meningiomas and the pulmonary metastases in both cases. These cases illustrate
      the importance of close neuroradiological follow-up to detect tumor recurrence in
      patients with atypical meningiomas WHO grade II even with clinically stable
      disease and should sensitize clinicians to late extracranial metastases of these
      tumors, especially to the lung. In an effort to elucidate common clinical
      features of metastatic meningiomas, especially to the lung, the literature was
      reviewed from 1995 to 2014, identifying a total of 45 published cases.

PMID- 25376228
TI  - Elevated fecal M2-pyruvate kinase in children with cystic fibrosis: a clue to the
      increased risk of intestinal malignancy in adulthood?
AB  - BACKGROUND AND AIM: Adult patients with cystic fibrosis (CF) have an increased
      risk of gastrointestinal malignancies. We hypothesized that increased intestinal
      cell turnover beginning in childhood may explain the increased risk of malignancy
      in early adulthood. Therefore, we aimed to measure fecal M2-pyruvate kinase (M2
      PK), a biomarker of intestinal cell turnover, in children with CF. To assess
      whether the increased cell turnover is secondary to intestinal inflammation, the
      secondary aims were to measure fecal calprotectin and evaluate its association
      with fecal M2-PK. METHODS: Fecal samples, for M2-PK and calprotectin
      measurements, were prospectively collected from children with CF and healthy
      controls (HC). RESULTS: Thirty-three children with CF (mean [standard deviation]
      7.3 [3.8] years old; 29 pancreatic insufficient [PI]) were enrolled and compared
      with 33 age-matched HC. Fecal M2-PK in CF patients (median [interquartile range,
      IQR]: 4.7 [1.5-9.7]) was greater than HC (1.0 [1.0-1.0] U/mL; P < 0.0001), and
      higher in PI (median [IQR]: 5.1 [1.8-13.7]) than pancreatic sufficient patients
      (1.0 [1.0-1.0] U/mL; P = 0.002). Fecal calprotectin was significantly elevated in
      CF than HC (median [IQR] 61.3 [43.8-143.8] vs 19.5 [19.5-35.1] mg/kg; P <
      0.0001). However, there was no correlation between fecal M2-PK and fecal
      calprotectin levels among subjects with CF (r = 0.29; P = 0.1). CONCLUSION:
      Increased intestinal cell turnover is present in children with PI CF. The lack of
      relationship between fecal M2-PK and calprotectin suggests that contributing
      factor(s) other than inflammation may be present.

PMID- 25376229
TI  - Regulation of the pannexin-1 promoter in the rat epididymis.
AB  - Pannexins (PANXs) are channel-forming proteins implicated in cellular
      communication through the secretion of biomolecules, such as ATP and glutamate.
      PANX1 and PANX3 are expressed in the male rat reproductive tract and their levels
      are regulated by androgens in the epididymis. There is currently no information
      on the regulation of the Panx1 promoter. The objective of the present study was
      to characterize the Panx1 promoter in order to understand its regulation in the
      epididymis. RNA ligase-mediated rapid amplification of cDNA ends identified three
      transcriptional start sites, at positions -443, -429, and -393. In silico
      analysis revealed that transcription was initiated downstream of binding sites
      for CREB and ETV4 transcription factors, in a CpG island context. To determine
      the importance of this region in gene transactivation, a 2-kb fragment of the
      promoter was cloned into a vector containing a luciferase reporter gene. Deletion
      constructs indicated that the highest transactivation levels were achieved with
      shorter constructs (-973 to -346 and -550 to -346). Electrophoretic mobility
      shift assay and supershifts indicated that both transcription factors were able
      to bind to the promoter region. Chromatin immunoprecipitation using rat caput
      epididymis cells confirmed the binding of ETV4 and CREB on the Panx1 promoter.
      Site mutation of either the ETV4 or CREB binding site decreased the
      transactivation of the reporter gene. Previous studies indicated that
      orchidectomy increased epididymal PANX1 levels. Likewise, we observed an increase
      in both ETV4 and CREB in orchidectomized rats. These results indicate that ETV4
      and cAMP response elements play a role in the transcriptional regulation of Panx1
      in the epididymis. 

PMID- 25376230
TI  - Tissue-specific stem cells in the myometrium and tumor-initiating cells in
      leiomyoma.
AB  - Tissue-specific (or somatic) stem cells constitute a subset of cells residing in
      normal adult tissues. By undergoing asymmetric division, they retain their
      ability to self-renew while producing daughter cells that go on to differentiate
      and play a role in tissue regeneration and repair. The human uterus consists
      primarily of endometrium and myometrium (the smooth muscle layer) that rapidly
      enlarges through its tremendous regenerative and remodeling capacity to
      accommodate the developing fetus. Such uterine enlargement and remodeling can
      take place repeatedly and cyclically over the course of a woman's reproductive
      life. These unique properties of the uterus suggest the existence of endometrial
      and myometrial stem cell systems. In addition, like somatic cells, tumor stem
      cells or tumor-initiating cells, a subset of cells within a tumor, retain the
      ability to reconstitute tumors. Uterine smooth muscle cells are thought to be the
      origin of leiomyomas that are the most common type of gynecologic tumor. Recent
      work has identified, isolated, and characterized putative stem/progenitor cells
      in the myometrium and in leiomyomas. Here, we review current studies of
      myometrial and leiomyoma stem/progenitor cells and provide a new paradigm for
      understanding myometrial physiology and pathology and how these cells might
      contribute to uterine remodeling during pregnancy and the formation of
      leiomyomas. The role of the WNT/CTNNB1 pathway in the pathogenesis of leiomyoma
      is also discussed. 

PMID- 25376231
TI  - Angiogenesis in the primate ovulatory follicle is stimulated by luteinizing
      hormone via prostaglandin E2.
AB  - Rapid angiogenesis occurs as the ovulatory follicle is transformed into the
      corpus luteum. To determine if luteinizing hormone (LH)-stimulated prostaglandin
      E2 (PGE2) regulates angiogenesis in the ovulatory follicle, cynomolgus macaques
      received gonadotropins to stimulate multiple follicular development and chorionic
      gonadotropin (hCG) substituted for the LH surge to initiate ovulatory events.
      Before hCG, vascular endothelial cells were present in the perifollicular stroma
      but not amongst granulosa cells. Endothelial cells entered the granulosa cell
      layer 24-36 h after hCG, concomitant with the rise in follicular PGE2 and prior
      to ovulation, which occurs about 40 h after hCG. Intrafollicular administration
      of the PG synthesis inhibitor indomethacin was coupled with PGE2 replacement to
      demonstrate that indomethacin blocked and PGE2 restored follicular angiogenesis
      in a single, naturally developed monkey follicle in vivo. Intrafollicular
      administration of indomethacin plus an agonist selective for a single PGE2
      receptor showed that PTGER1 and PTGER2 agonists most effectively stimulated
      angiogenesis within the granulosa cell layer. Endothelial cell tracing and three
      dimensional reconstruction indicated that these capillary networks form via
      branching angiogenesis. To further explore how PGE2 mediates follicular
      angiogenesis, monkey ovarian microvascular endothelial cells (mOMECs) were
      isolated from ovulatory follicles. The mOMECs expressed all four PGE2 receptors
      in vitro. PGE2 and all PTGER agonists increased mOMEC migration. PTGER1 and
      PTGER2 agonists promoted sprout formation while the PTGER3 agonist inhibited
      sprouting in vitro. While PTGER1 and PTGER2 likely promote the formation of new
      capillaries, each PGE2 receptor may mediate aspects of PGE2's actions and,
      therefore, LH's ability to regulate angiogenesis in the primate ovulatory
      follicle.

PMID- 25376233
TI  - Lenition of intervocalic alveolar fricatives in Catalan and Spanish.
AB  - We offer an acoustic study of variation in the realization of intervocalic
      alveolar fricatives in Catalan and Spanish. We consider the effects of
      phonological inventory (Catalan has a distinction between /s/ and /z/ that
      Spanish lacks) and position in word (i.e. effects of word boundaries). An
      analysis of a corpus of Map Task interviews in Catalan and Spanish revealed that
      Spanish word-medial and initial intervocalic /s/ segments are shorter than in
      Catalan. Whereas our results are consistent with the predictions of theories
      incorporating functional principles (i.e. contrast preservation), we also
      consider other possible explanations of the facts. The analysis also revealed
      that Spanish word-final intervocalic /s/ segments are weaker along the two
      dimensions that we examined (duration and voicing) than their initial and medial
      counterparts. We suggest that this apparently morphological effect on lenition
      has an articulatory explanation in terms of gestural coordination.

PMID- 25376232
TI  - Transcriptomic diversification of developing cumulus and mural granulosa cells in
      mouse ovarian follicles.
AB  - Cumulus cells and mural granulosa cells (MGCs) have functionally distinct roles
      in antral follicles, and comparison of their transcriptomes at a global and
      systems level can propel future studies on mechanisms underlying their functional
      diversity. These cells were isolated from small and large antral follicles before
      and after stimulation of immature mice with gonadotropins, respectively. Both
      cell types underwent dramatic transcriptomic changes, and differences between
      them increased with follicular growth. Although cumulus cells of both stages of
      follicular development are competent to undergo expansion in vitro, they were
      otherwise remarkably dissimilar with transcriptomic changes quantitatively
      equivalent to those of MGCs. Gene ontology analysis revealed that cumulus cells
      of small follicles were enriched in transcripts generally associated with
      catalytic components of metabolic processes, while those from large follicles
      were involved in regulation of metabolism, cell differentiation, and adhesion.
      Contrast of cumulus cells versus MGCs revealed that cumulus cells were enriched
      in transcripts associated with metabolism and cell proliferation while MGCs were
      enriched for transcripts involved in cell signaling and differentiation. In vitro
      and in vivo models were used to test the hypothesis that higher levels of
      transcripts in cumulus cells versus MGCs is the result of stimulation by oocyte
      derived paracrine factors (ODPFs). Surprisingly ~48% of transcripts higher in
      cumulus cells than MGCs were not stimulated by ODPFs. Those stimulated by ODPFs
      were mainly associated with cell division, mRNA processing, or the catalytic
      pathways of metabolism, while those not stimulated by ODPFs were associated with
      regulatory processes such as signaling, transcription, phosphorylation, or the
      regulation of metabolism.

PMID- 25376236
TI  - Propranolol-induced Somnambulism: A Case-report in a Patient with Essential
      Tremor.

PMID- 25376234
TI  - Delivery of a functional anti-trypanosome Nanobody in different tsetse fly
      tissues via a bacterial symbiont, Sodalis glossinidius.
AB  - BACKGROUND: Sodalis glossinidius, a vertically transmitted microbial symbiont of
      the tsetse fly, is currently considered as a potential delivery system for anti
      trypanosomal components that reduce or eliminate the capability of the tsetse fly
      host to transmit parasitic trypanosomes, an approach also known as
      paratransgenesis. An essential step in developing paratransgenic tsetse is the
      stable colonization of adult flies and their progeny with recombinant Sodalis
      bacteria, expressing trypanocidal effector molecules in tissues where the
      parasite resides. RESULTS: In this study, Sodalis was tested for its ability to
      deliver functional anti-trypanosome nanobodies (Nbs) in Glossina morsitans
      morsitans. We characterized the in vitro and in vivo stability of recombinant
      Sodalis (recSodalis) expressing a potent trypanolytic nanobody, i.e. Nb_An46. We
      show that recSodalis is competitive with WT Sodalis in in vivo conditions and
      that tsetse flies transiently cleared of their endogenous WT Sodalis population
      can be successfully repopulated with recSodalis at high densities. In addition,
      vertical transmission to the offspring was observed. Finally, we demonstrated
      that recSodalis expressed significant levels (ng range) of functional Nb_An46 in
      different tsetse fly tissues, including the midgut where an important
      developmental stage of the trypanosome parasite occurs. CONCLUSIONS: We
      demonstrated the proof-of-concept that the Sodalis symbiont can be genetically
      engineered to express and release significant amounts of functional anti
      trypanosome Nbs in different tissues of the tsetse fly. The application of this
      innovative concept of using pathogen-targeting nanobodies delivered by insect
      symbiotic bacteria could be extended to other vector-pathogen systems.

PMID- 25376235
TI  - Preoperative left ventricular ejection fraction and left atrium reverse
      remodeling after mitral regurgitation surgery.
AB  - BACKGROUND: Left atrium enlargement has been associated with cardiac events in
      patients with mitral regurgitation (MR). Left atrium reverse remodeling (LARR)
      occur after surgical correction of MR, but the preoperative predictors of this
      phenomenon are not well known. It is therefore important to identify preoperative
      predictors for postoperative LARR. METHODS: We enrolled 62 patients with chronic
      severe MR (prolapse or flail leaflet) who underwent successful mitral valve
      surgery (repair or replacement); all with pre- and postoperative
      echocardiography. LARR was defined as a reduction in left atrium volume index
      (LAVI) of >= 25%. Stepwise multiple regression analysis was used to identify
      independent predictors of LARR. RESULTS: LARR occurred in 46 patients (74.2%),
      with the mean LAVI decreasing from 85.5 mL/m2 to 49.7 mL/m2 (p <0.001). These
      patients had a smaller preoperative left ventricular systolic volume (p =0.022)
      and a higher left ventricular ejection fraction (LVEF) (p =0.034). LVEF was
      identified as the only preoperative variable significantly associated with LARR
      (odds ratio, 1.086; 95% confidence interval, 1.002-1.178). A LVEF cutoff value of
      63.5% identified patients with LARR of >= 25% with a sensitivity of 71.7% and a
      specificity of 56.3%. CONCLUSIONS: LARR occurs frequently after mitral valve
      surgery and is associated with preoperative LVEF higher than 63.5%.

PMID- 25376237
TI  - Cosolvent and crowding effects on the polymerization kinetics of actin.
AB  - We studied the effects of kosmotropic and chaotropic cosolvents, trimethylamine-N
      oxide (TMAO) and urea, as well as crowding agents (dextran) on the polymerization
      reaction of actin. Time-lapse fluorescence intensity and anisotropy experiments
      were carried out to yield information about the kinetics of the polymerization
      process. To also quantitatively describe the effects, cosolvents and crowding
      impose on the underlying rate constants of the G-to-F-transformation, an
      integrative stochastic simulation model was applied. Drastic and diverse changes
      in the lag phase and association rates as well as the critical actin
      concentration were observed under different solvent conditions. The association
      rate constant is drastically increased by TMAO but decreased by urea. In mixtures
      of these osmolytes, TMAO counteracts not only the deleterious effect of urea on
      protein structure and stability, but also on the protein-protein interactions in
      the course of actin polymerization. Owing to the excluded volume effect, cell
      like macromolecular crowding conditions increase the nucleation and association
      rates by one order of magnitude. Our results clearly reveal the pronounced
      sensitivity of the actin polymerization reaction to changes in cosolvent
      conditions and the presence of macromolecular crowding, and suggest that such
      effects should be taken into account in any discussion of the actin
      polymerization reaction in vivo. 

PMID- 25376239
TI  - Role of the MAPKs/TGF-beta1/TRAF6 signaling pathway in atrial fibrosis of
      patients with chronic atrial fibrillation and rheumatic mitral valve disease.
AB  - OBJECTIVE: Atrial remodeling is involved in atrial fibrillation (AF), and atrial
      fibrosis is an important marker of atrial remodeling. On the basis of our
      previous animal studies of the mitogen-activated protein kinases
      (MAPKs)/transforming growth factor beta1 (TGF-beta1)/tumor necrosis factor
      pathway in atrial fibrosis, we undertook investigation of this signaling pathway
      in atrial fibrosis of patients with chronic AF (CAF) and rheumatic mitral valve
      disease. METHODS: Fifty-six rheumatic mitral valve disease patients were divided
      into CAF (course of AF >12 months) and sinus rhythm (SR) groups. Left atrial
      appendage tissue was collected during heart surgery, and pathological examination
      was done to evaluate atrial fibrosis. Protein and mRNA expression of TGF-beta1,
      TRAF6 and connective tissue growth factor (CTGF) and protein expression of
      phosphorylated MAPKs and TGF-beta-activated kinase 1 (TAK1) were measured.
      RESULTS: Histological examination revealed that the severity of atrial fibrosis
      in CAF patients was significantly higher, mRNA and protein expression of TGF
      beta1, TRAF6 and CTGF in CAF were significantly increased, and the protein
      expression of phosphorylated MAPKs and TAK1 was significantly increased in CAF
      compared to SR patients. CONCLUSION: The MAPKs/TGF-beta1/TRAF6 signaling pathway
      is involved in atrial fibrosis of CAF patients, and TRAF6 may become a new target
      for the treatment of atrial fibrosis.

PMID- 25376238
TI  - Updated canine infection rates for Dirofilaria immitis in areas of Brazil
      previously identified as having a high incidence of heartworm-infected dogs.
AB  - BACKGROUND: Canine heartworm infections were frequently diagnosed in Brazil
      before the new millennium. After the year 2000, the frequency of diagnosis showed
      a sharp decline; however, a few years later, new evidence indicated that the
      parasite was still present and that canine infection rates seemed to be
      increasing. Therefore, an updated survey of canine heartworm prevalence was
      conducted in several locations in south, southeast, and northeast Brazil.
      METHODS: Dogs from 15 locations having previously reported a high prevalence of
      heartworm infection were included in the survey according to defined criteria,
      including the absence of treatment with a macrocyclic lactone for at least 1
      year. Blood samples from 1531 dogs were evaluated by an in-clinic
      immunochromatography test kit (Witness(r) Heartworm, Zoetis, USA) for detection
      of Dirofilaria immitis antigen. At each location, epidemiologic data, including
      physical characteristics and clinical signs reported by owners or observed by
      veterinarians, were recorded on prepared forms for tabulation of results by
      location, clinical signs, and physical characteristics. RESULTS: The overall
      prevalence of canine heartworm infection was 23.1%, with evidence of heartworm
      infected dogs detected in all 15 locations studied. There was a tendency for
      higher prevalence rates in environmentally protected areas, despite some
      locations having less-than-ideal environmental temperatures for survival of
      vector mosquitoes. Among physical characteristics, it was noted that dogs with
      predominantly white hair coats and residing in areas with a high (>=20%)
      prevalence of heartworm were less likely to have heartworm infection detected by
      a commercial heartworm antigen test kit than were dogs with other coat colors. In
      general, dogs older than 2 years were more frequently positive for D. immitis
      antigen than were younger dogs. Clinical signs of heartworm infections were rare
      or owners were unable to detect them, and could not be used for reliable
      prediction of the presence of heartworm. CONCLUSIONS: These results indicate that
      the prevalence of D. immitis has increased in these areas of Brazil over the past
      few years. Small animal practitioners in these areas should include routine
      screening tests for heartworm infections in every dog's annual evaluation
      protocol and make sure to have uninfected dogs on prevention.

PMID- 25376240
TI  - A 3D MOF showing unprecedented solvent-induced single-crystal-to-single-crystal
      transformation and excellent CO2 adsorption selectivity at room temperature.
AB  - A water stable porous 3D metal-organic framework, [Cu3L2(MU3-OH)2(MU2-H2O)].2DMA
      (1, mother crystal, H2L = 2,2'-dinitrobiphenyl-4,4'-dicarboxylic acid, DMA = N,N
      dimethylacetamide), shows unprecedented irreversible solvent-induced
      substitutions of bridging aqua ligands and guest-exchanges in single-crystal-to
      single-crystal (SCSC) transformations at room temperature (RT), producing
      quantitatively three daughter crystals, [Cu3L2(MU3-OH)2].2S (2: 2A, S = acetone;
      2B, S = 2-propanol; 2C, S = 2-butanol), which exhibit reversible interconversion
      by guest-exchanges at RT in SCSC transformations. MOF 1 shows excellent
      separation selectivity (128) of CO2/N2 at RT and is a better sorbent of micro
      solid-phase extraction (MU-SPE) than currently known benchmark ZIF-8. 

PMID- 25376241
TI  - beta-CateninC429S mice exhibit sterility consequent to spatiotemporally sustained
      Wnt signalling in the internal genitalia.
AB  - Wnt/beta-catenin signalling regulates numerous developmental and homeostatic
      processes. Ctnnb1 (also known as beta-catenin) is the only protein that transmits
      signals from various Wnt ligands to downstream genes. In this study, we report
      that our newly established mouse strain, which harbours a Cys429 to Ser missense
      mutation in the beta-catenin gene, exhibited specific organ defects in contrast
      to mice with broadly functioning Wnt/beta-catenin signalling. Both homozygous
      mutant males and females produced normal gametes but were infertile because of
      abnormal seminal vesicle and vaginal morphogenesis. An ins-TOPGAL transgenic
      reporter spatiotemporally sustained Wnt/beta-catenin signalling during the
      corresponding organogenesis. Therefore, beta-catenin(C429S) should provide new
      insights into beta-catenin as a universal component of Wnt/beta-catenin signal
      transduction. 

PMID- 25376242
TI  - Serum beta2-microglobulin correlates positively with left ventricular hypertrophy
      in long-term hemodialysis patients.
AB  - BACKGROUND/AIMS: beta2-Microglobulin (beta2-MG) is a major protein component of
      dialysis-related amyloidosis. In long-term hemodialysis (HD) patients, beta2-MG
      amyloid deposits not only in osteoarticular tissues, but also in systemic
      tissues, including the heart. The purpose of this study was to investigate the
      relationship between serum beta2-MG concentrations and echocardiographic
      parameters in long-term HD patients in a cross-sectional study. METHODS:
      Measurement of serum beta2-MG concentrations and echocardiography were performed
      in 251 patients who had undergone HD therapy for more than 10 years. RESULTS: The
      left ventricular mass index (LVMI) of the higher serum beta2-MG (>=30 mg/l) group
      was significantly higher than that of the lower serum beta2-MG (<30 mg/l) group
      (151.5 +/- 45.7 vs. 137.0 +/- 44.5 g/m(2), p = 0.020). In simple regression
      analyses, serum beta2-MG concentrations correlated significantly and positively
      with interventricular septum thickness (IVST) (r = 0.215, p < 0.001), posterior
      left ventricular wall thickness (PWT) (r = 0.249, p < 0.001), left ventricular
      wall thickness (LVWT) (r = 0.252, p < 0.001), relative wall thickness (RWT) (r =
      0.153, p = 0.015) and LVMI (r = 0.171, p = 0.007). Multiple regression analyses
      revealed that serum beta2-MG concentrations correlated significantly and
      positively with IVST, PWT, LVWT and RWT. CONCLUSION: Serum beta2-MG
      concentrations correlated significantly and positively with the echocardiographic
      parameters of left ventricular hypertrophy (LVH) in long-term HD patients. Thus,
      deposition of beta2-MG amyloid in the heart may be associated with LVH
      progression.

PMID- 25376243
TI  - The glomerular parietal epithelial cell's responses are influenced by SM22 alpha
      levels.
AB  - BACKGROUND: Studies have shown in several diseases initially affecting podocytes,
      that the neighboring glomerular parietal epithelial cells (PECs) are secondarily
      involved. The PEC response might be reparative under certain circumstances, yet
      injurious under others. The factors governing these are not well understood. We
      have shown that SM22alpha, an actin-binding protein considered a marker of smooth
      muscle differentiation, is upregulated in podocytes and PECs in several models of
      podocyte disease. However, the impact of SM22alpha levels on PECs is not known.
      METHODS: Experimental glomerular disease, characterized by primary podocyte
      injury, was induced in aged-matched SM22alpha+/+ and SM22alpha-/-mice by
      intraperitoneal injection of sheep anti-rabbit glomeruli antibody. Immunostaining
      methods were employed on days 7 and 14 of disease. RESULTS: The number of PEC
      transition cells, defined as cells co-expressing a PEC protein (PAX2) and
      podocyte protein (Synaptopodin) was higher in diseased SM22alpha-/-mice compared
      with SM22alpha+/+mice. WT1 staining along Bowman's capsule is higher in diseased
      SM22alpha-/-mice. This was accompanied by increased PEC proliferation (measured
      by ki-67 staining), and an increase in immunostaining for the progenitor marker
      NCAM, in a subpopulation of PECs in diseased SM22alpha-/-mice. In addition,
      immunostaining for vimentin and alpha smooth muscle actin, markers of epithelial
      to-mesenchymal transition (EMT), was lower in diseased SM22alpha-/-mice compared
      to diseased SM22alpha+/+mice. CONCLUSION: SM22alpha levels may impact how PECs
      respond following a primary podocyte injury in experimental glomerular disease.
      Absent/lower levels favor an increase in PEC transition cells and PECs expressing
      a progenitor marker, and a lower EMT rate compared to SM22alpha+/+mice, where
      SM22 levels are markedly increased in PECs.

PMID- 25376244
TI  - Single- and multiple dose pharmacokinetics and multiple dose pharmacodynamics of
      oral ABT-116 (a TRPV1 antagonist) in dogs.
AB  - Six dogs were used to determine single and multiple oral dose pharmacokinetics of
      ABT-116. Blood was collected for subsequent analysis prior to and at 15, 30 min
      and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose
      of ABT-116. Results showed a half-life of 6.9 h, k(el) of 0.1/h, AUC of 56.5
      MUg.h/mL, T(max) of 3.7 h, and C(max) of 3.8 MUg/mL. Based on data from this
      initial phase, a dose of 10 mg/kg of ABT-116 (no placebo control) was selected
      and administered to the same six dogs once daily for five consecutive days.
      Behavioral observations, heart rate, respiratory rate, temperature, thermal and
      mechanical (proximal and distal limb) nociceptive thresholds, and blood
      collection were performed prior to and 4, 8, and 16 h after drug administration
      each day. The majority of plasma concentrations were above the efficacious
      concentration (0.23 MUg/mL previously determined for rodents) for analgesia
      during the 24-h sampling period. Thermal and distal limb mechanical thresholds
      were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body
      temperature increased on the first day of dosing. Results suggest adequate
      exposure and antinociceptive effects of 10 mg/kg ABT-116 following oral delivery
      in dogs.

PMID- 25376245
TI  - Penetration of topical chloramphenicol into the anterior chamber: response.

PMID- 25376246
TI  - Guidelines for the reporting of clinical research.

PMID- 25376247
TI  - Proteinuria early in the development of hypertension.

PMID- 25376248
TI  - Can the development of severe hypertension be predicted?

PMID- 25376249
TI  - Predictive value of endothelial dysfunction: a call to action.

PMID- 25376250
TI  - Cost-effectiveness of therapeutic drug monitoring in patients with resistant
      hypertension and improving patients' adherence.

PMID- 25376251
TI  - Diastolic dysfunction, blood pressure and obesity: new insights from a general
      population.

PMID- 25376252
TI  - Validation and comparison of three formulae to estimate sodium and potassium
      excretion from a single-morning fasting urine compared to 24-h measures in 11
      countries.

PMID- 25376253
TI  - Can sodium excretion from single fasting morning urine really be used for
      estimation of dietary sodium intake?

PMID- 25376254
TI  - Reply to both letters.

PMID- 25376255
TI  - Determination of the clinical egg allergy phenotypes using component-resolved
      diagnostics.
AB  - IgE-mediated egg allergy presents as one of the most common food allergies in
      children and is a food which is widely consumed all over the world. Measurement
      of egg white-specific IgE levels has been shown to be a poor predictor of
      clinical phenotypes of egg allergy, including to raw egg white, but particularly
      to baked or cooked egg. Egg white and yolk contain more than 20 different
      glycoproteins, including ovomucoid, ovalbumin, ovotransferrin, alpha-livetin, and
      the newly identified Gal d 6. Recent developments in component-resolved
      diagnostic technology, including microarrays, have enabled us to improve the way
      in which we diagnose food allergy. This technology allows us to measure specific
      IgE antibodies to individual egg allergens which have been highly purified.
      Characterization of the major egg allergens could help profile the relevant
      binding epitopes to each region and may also help diagnose the different clinical
      phenotypes of egg allergy. 

PMID- 25376256
TI  - If I have seen further it is by standing on the shoulders of giants: finding a
      voice, a positive future for nursing.

PMID- 25376257
TI  - Cranial nerve injuries with supraglottic airway devices: a systematic review of
      published case reports and series.
AB  - Cranial nerve injuries are unusual complications of supraglottic airway use.
      Branches of the trigeminal, glossopharyngeal, vagus and the hypoglossal nerve may
      all be injured. We performed a systematic review of published case reports and
      case series of cranial nerve injury from the use of supraglottic airway devices.
      Lingual nerve injury was the most commonly reported (22 patients), followed by
      recurrent laryngeal (17 patients), hypoglossal (11 patients), glossopharyngeal
      (three patients), inferior alveolar (two patients) and infra-orbital (one
      patient). Injury is generally thought to result from pressure neuropraxia.
      Contributing factors may include: an inappropriate size or misplacement of the
      device; patient position; overinflation of the device cuff; and poor technique.
      Injuries other than to the recurrent laryngeal nerve are usually mild and self
      limiting. Understanding the diverse presentation of cranial nerve injuries helps
      to distinguish them from other complications and assists in their management. 

PMID- 25376258
TI  - Cell-bound exopolysaccharides of Lactobacillus brevis KB290 enhance cytotoxic
      activity of mouse splenocytes.
AB  - AIMS: This study aimed to identify the main active component of Lactobacillus
      brevis KB290 (KB290) that is responsible for enhanced cell-mediated cytotoxic
      activity of mouse splenocytes Live KB290, a probiotic strain derived from a
      Japanese traditional pickle, was previously reported to modulate innate immune
      responses as affecting on cell-mediated cytotoxic activity of mouse splenocytes.
      METHODS AND RESULTS: We used live KB290, heat-killed KB290, a derivative strain
      (Lact. brevis KB392) with different amounts of cell-bound exopolysaccharide (EPS
      b), and a crude extract of EPS-b from KB290 cell surface. Female BALB/c mice were
      fed a diet containing 10(10) CFU live KB290, 10(10) CFU live KB392, 15 mg heat
      killed KB290 or 600 MUg crude extract of EPS-b for 1 day. Live KB290 (P < 0.01),
      heat-killed KB290 (P < 0.05) and crude EPS-b at 600 MUg (P < 0.05) per mouse
      significantly enhanced cytotoxic activity; however, live KB392 had no effect.
      CONCLUSIONS: Both live and heat-killed KB290 and crude EPS-b significantly
      enhanced cytotoxic activity of mouse splenocytes. SIGNIFICANCE AND IMPACT OF THE
      STUDY: We demonstrated that EPS-b produced by KB290 has a critical role in
      enhancing cell-mediated cytotoxic activity in mouse spleen.

PMID- 25376259
TI  - Outsourcing cytological samples to a referral laboratory for EGFR testing in non
      small cell lung cancer: does theory meet practice?
AB  - OBJECTIVE: Guidelines from the College of American Pathologists (CAP), the
      International Association for the Study of Lung Cancer (IASLC) and the
      Association for Molecular Pathology (AMP) consider cytology suitable for testing
      epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. The
      guidelines recommend that cytopathologists first discuss the possibility of
      testing squamous cell carcinomas (SqCC) in multidisciplinary meetings. Second,
      cell blocks should be analysed rather than smear preparations and, third,
      specimens should be sent to external molecular laboratories within three working
      days of receiving requests. This study monitored how these recommendations are
      met in practice. METHODS: Our laboratory received 596 requests from cytologists
      from 13 different institutions. For each case, the cytological diagnosis,
      cytopreparation type, and time between the request and sample mailing were
      compared with the recommendations. RESULTS: Of the 596 samples, 32 (5.4%) had
      been reported as SqCC. Three of these (9.4%) showed EGFR mutation. Cytological
      slides, either ThinPrep(TM) (51.2%) or direct smears (43.2%), were more
      frequently received than cell blocks (5.7%). The mean time between the
      oncologist's request and specimen dispatching was 5.8 working days. CONCLUSIONS:
      The occurrence of mutations in samples reported as SqCC was higher than expected.
      This questions the reliability of the original diagnosis, which reinforced the
      recommendation to evaluate the opportunity for testing non-adenocarcinoma
      cytology on a case-by-case basis. In spite of CAP/IASLC/AMP recommendations, cell
      blocks were underutilized for EGFR testing, but cytological slides were suitable
      for DNA analyses. Significant efforts are needed to avoid delays in outsourcing
      cytological samples for EGFR testing.

PMID- 25376260
TI  - Lung ultrasonography may provide an indirect estimation of lung porosity and
      airspace geometry.
AB  - BACKGROUND: Echographic vertical artifacts (B-lines) in chest ultrasonography
      have often been associated with pathological patterns. A scientifically sound
      explanation of these artifacts has not yet been proposed. OBJECTIVES: The
      'spongy' nature of the lung in its liquid and solid components and the changes
      that take place in peripheral airspace (PAS) geometry might be the key point to
      understanding these phenomena. METHODS: Six excised right rabbit lungs were
      obtained. Each lung underwent direct ultrasound evaluation in two different
      conditions: at complete tissue elastic recoil volume and at pulmonary expansion
      volume achieved by applying a constant positive pressure of 12 cm H2O. Lung
      volumes and densities were reported in both conditions. Histological examination
      was performed on three naturally collapsed lungs and on three lungs under
      positive pressure inflation after having been fixed in formalin solution.
      RESULTS: Mean volumes of naturally collapsed lungs and fixed expanded lungs were
      11.2 +/- 0.36 and 44.83 +/- 3.03 ml, respectively. Mean densities were 0.622 +/-
      0.016 and 0.155 +/- 0.007 g/ml, respectively. Ultrasound evaluation of collapsed
      lungs showed dense vertical artifacts and a 'white lung' pattern, while the
      evaluation of expanded lungs showed hyperechoic line and horizontal artifacts of
      reflection. Histological evaluation showed a different PAS geometry in collapsed
      lungs caused by alveolar size reduction and shape changes with unfolded and
      closed units modifying the peripheral porosity of the frothy nature of the lung.
      CONCLUSIONS: Airspace geometry, frothy nature and porosity are the determinants
      of the different behavior of ultrasound interacting with the subpleural lung
      parenchyma. Chest ultrasound may thus be interpreted as an indirect 'estimator'
      of lung porosity.

PMID- 25376262
TI  - Osteocalcin and the pituitary-gonadal axis in older men: a population-based
      study.
AB  - OBJECTIVE: Osteocalcin is a well-known marker of bone formation. Recently, mice
      lacking osteocalcin or its receptor were reported to be subfertile with low
      testosterone and high luteinizing hormone concentrations. In parallel, in humans,
      a loss-of-function mutation of the osteocalcin receptor was associated with
      hypergonadotropic hypogonadism. This suggests that osteocalcin is necessary for
      normal pituitary-gonadal axis function. Our objective was to determine the
      association between physiological variations in osteocalcin and the pituitary
      gonadal axis in older men. DESIGN AND PATIENTS: Data were used from the
      Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study in a
      representative sample of the older Dutch population (65-88 years). MEASUREMENTS:
      Serum levels of total (T), free (FT) and bioavailable (bioT) testosterone,
      luteinizing hormone (LH) and osteocalcin were determined. Data were analysed
      using linear regression analyses and adjusted for age, BMI, 25-hydroxyvitamin D,
      parathyroid hormone and vitamin K antagonist use. RESULTS: A total of 614 men
      participated in the study. The median age was 75.4 (69.8-81.2) years, and the
      median osteocalcin level was 1.8 (1.3-2.4) nmol/l. Serum osteocalcin was
      inversely associated with FT (adjusted B = -0.22 +/- 0.09 ng/dl, P = 0.012) and
      bioT (adjusted B = -0.26 +/- 0.08 nmol/l, P < 0.01), but not with total T.
      Furthermore, osteocalcin was positively associated with LH (adjusted B = 0.09 +/-
      0.03 U/l, P < 0.01). CONCLUSIONS: Serum osteocalcin was negatively associated
      with free and bioavailable testosterone and positively with luteinizing hormone
      levels.

PMID- 25376263
TI  - Incidence of adenoviral DNAemia in Polish adults undergoing allogeneic
      haematopoietic stem cell transplantation.
AB  - Human adenoviruses (HAdV) are important viral pathogens recognized increasingly
      in immunocompromised hosts, especially in allogeneic haematopoietic stem cell
      transplant recipients (alloHSCT). The clinical spectrum of HAdV disease ranges
      from asymptomatic viraemia and mild self-limiting disease to lower respiratory
      tract infection, multi-organ involvement and even death. Early detection and
      quantification of HAdV in peripheral blood using real-time PCR (qPCR) assay has
      been suggested as a useful monitoring tool, but is seldom used for regular
      surveillance of HAdV in haematology centers. A group of 112 alloHSCT recipients
      from two hospitals in Warsaw (Poland) was examined in the early post-transplant
      period using a quantitative qPCR assay. A total of 1,245 serum samples were
      evaluated for presence of HAdV DNA in patients where 66 (59 %) patients received
      grafts from unrelated donors whereas the other 46 (41 %) from sibling donors.
      HAdV sequences were detected in 64 (57 %) of the 112 patients. In 22 of all
      patients (20 %) HAdV DNA was detected only in a single positive sample, while 42
      (37 %) had positive results in two or more subsequent sera. In total, DNAemia was
      present in 202 sera samples (16 %) with median time to observation of 47 days.
      Graft-versus-host disease (GvHD) was observed in 18 (28 %) adenovirus-infected
      transplant recipients and a significant correlation between HAdV infections and
      GvHD clinical presentation was found (p = 0.018). There is a high prevalence of
      HAdV infections in HSCT recipients in Poland during early post-transplant period.
      In consequence, we could only speculate if HAdV DNAemia could be also related to
      GvHD symptoms, enforcing the important pathogenic role of these viral infections
      in clinical complications post-alloHSCT. 

PMID- 25376264
TI  - Helicobacter-negative gastritis: a distinct entity unrelated to Helicobacter
      pylori infection.
AB  - BACKGROUND: Helicobacter-negative gastritis is diagnosed when no organisms are
      detected in a gastric mucosa with typical features of Helicobacter gastritis (Hp
      gastritis). If Helicobacter-negative gastritis consisted mostly of 'missed'
      Helicobacter infections, its prevalence should represent a constant percentage of
      these infections in a population, and their clinico-epidemiological features
      would overlap. AIM: To compare the epidemiologic patterns of Hp-positive and Hp
      negative gastritis. METHODS: From a pathology database, we extracted demographic,
      clinical and histopathological data from patients with gastric biopsies (1.2008
      12.2013). We allocated patients to high (>=12%) and low (<=6%) H. pylori
      prevalence regions defined by ZIP code-based data. The prevalence of H. pylori
      positive and -negative gastritis by sex, age and state were expressed as a per
      cent of the total study population stratified accordingly. RESULTS: Of 895 323
      patients, 10.6% had Hp-gastritis and 1.5% Helicobacter-negative gastritis. Hp
      gastritis, but not Helicobacter-negative gastritis, was more common in males than
      females (OR 1.17, 95% CI: 1.16-1.19). While Hp-gastritis was more prevalent in
      high than in low-prevalence areas (OR 3.65, 95% CI: 3.57-3.74), Helicobacter
      negative gastritis was only minimally affected by the underlying H. pylori
      prevalence (1.7% vs. 1.5%). The age-specific prevalence of Hp-gastritis peaked in
      the 4th to 5th decades; Helicobacter-negative gastritis exhibited a low and
      relatively flat pattern. The geographic distribution of H. pylori-positive and 
      negative gastritis showed no significant correlation. Intestinal metaplasia was
      found in 13.0% of patients with Hp-gastritis and in 6.1% of those with
      Helicobacter-negative gastritis (OR 0.43, 95% CI: 0.40-0.47). CONCLUSION: These
      data suggest that Helicobacter-negative gastritis is, in the vast majority of
      cases, a nosologically and epidemiologically distinct entity that deserves
      further investigation.

PMID- 25376265
TI  - External and internal reality: the impact of the current socio-economic crisis on
      the analytic dyad.
AB  - This paper addresses the impact of the current economic crisis on the psychic
      functioning of the patient and the analyst, their relationship and collaboration.
      This intrusion of 'external reality' is multidimensional, and thus with multiple
      meanings. The critical role of the economic factor brings various dimensions of
      money into play, such as self-preservation, power as well as aspects of
      psychosexual development. In addition, the crisis involves symbolic loss of basic
      ideals such as honesty and social responsibility. Patient and analyst are
      affected in similar and different ways in their respective roles as well as
      according to the specific intrapsychic functioning of each. Moreover, unique
      characteristics of the crisis often create a crisis in the analysis. In order to
      avoid deformation of the analytic relationship, the analytic dyad must examine
      and work through the multiple meanings of the crisis as well as the meaning of
      the impact of the crisis on the analytic relationship for both patient and
      analyst. This complex transference- countertransference interplay poses specific
      challenges to the analyst. After discussion of these issues, clinical material is
      presented that demonstrates how they appear in analytic practice today. 

PMID- 25376266
TI  - Combined chelation therapy with daily oral deferiprone and twice-weekly
      subcutaneous infusion of desferrioxamine in children with beta-thalassemia: 3
      year experience.
AB  - OBJECTIVE: To study the efficacy of combined treatment with oral and subcutaneous
      iron chelators. MATERIAL AND METHODS: 50-100 mg/kg/day of oral deferiprone (DFP)
      combined with 40 mg/kg/dose s.c. desferrioxamine (DFO) twice weekly were given to
      transfusion-dependent beta-thalassemia children. RESULTS: Enrolled patients (9
      with beta-thalassemia major and 33 with beta-thalassemia hemoglobin E), ranging
      from 3 to 18 years in age, were divided into 3 groups; group 1 ferritin >=1,000
      2,500 ng/ml (n = 10), group 2 ferritin >2,500-4,000 ng/ml (n = 23) and group 3
      ferritin >4,000 ng/ml (n = 9). Of the 42 patients, 28 reached the 36-month follow
      up. Ten patients whose ferritin declined <15% while receiving 100 mg/kg/day of
      DFP were considered nonresponders. The median age and previous transfusion
      duration before enrollment were significantly higher in nonresponders than
      responders (p = 0.04 and 0.003, respectively). The responders exhibited a
      significant fall in median ferritin levels from 2,954.6 to 936.6 ng/ml (p <
      0.001). Time to a significant decrease in serum ferritin among responders was 6
      months. In 13 patients, 16 episodes of adverse events occurred: hemophagocytosis
      with cytopenia (n = 1), neutropenia (n = 2), thrombocytopenia (n = 2), elevated
      alanine aminotransferase (n = 5), elevated serum creatinine (n = 1), proteinuria
      (n = 1) and gastrointestinal discomfort (n = 4). CONCLUSION: Combination therapy
      with daily oral DFP and subcutaneous DFO twice weekly is a safe and effective
      alternative to chelation monotherapy in beta-thalassemia children.

PMID- 25376267
TI  - Randomized, double-blind trial of anidulafungin versus fluconazole for
      prophylaxis of invasive fungal infections in high-risk liver transplant
      recipients.
AB  - Invasive fungal infections (IFIs) are a common complication in liver transplant
      recipients. There are no previous randomized trials of an echinocandin for the
      prevention of IFIs in solid organ transplant recipients. In a randomized, double
      blind trial conducted at University-affiliated transplant centers, 200 high-risk
      liver transplant recipients (100 patients per group) received either
      anidulafungin or fluconazole for antifungal prophylaxis. Randomization was
      stratified by Model for End-Stage Liver Disease score >=30 and receipt of a
      pretransplant antifungal agent. The primary end point was IFI in a modified
      intent-to-treat analysis. The overall incidence of IFI was similar for the
      anidulafungin (5.1%) and the fluconazole groups (8.0%) (OR 0.61, 95% CI 0.19
      1.94, p = 0.40). However, anidulafungin prophylaxis was associated with less
      Aspergillus colonization or infection (3% vs. 9%, p = 0.08), lower breakthrough
      IFIs among patients who had received pretransplant fluconazole (0% vs. 27%, p =
      0.07), and fewer cases of antifungal resistance (no cases vs. 5 cases). Both
      drugs were well-tolerated. Graft rejection, fungal-free survival, and mortality
      were similar for both groups. Thus, anidulafungin and fluconazole have similar
      efficacy for antifungal prophylaxis in most liver transplant recipients.
      Anidulafungin may be beneficial if the patient has an increased risk for
      Aspergillus infection or received fluconazole before transplantation. 

PMID- 25376268
TI  - The origin of representational drawing: a comparison of human children and
      chimpanzees.
AB  - To examine the evolutional origin of representational drawing, two experiments
      directly compared the drawing behavior of human children and chimpanzees. The
      first experiment observed free drawing after model presentation, using imitation
      task. From longitudinal observation of humans (N = 32, 11-31 months), the
      developmental process of drawing until the emergence of shape imitation was
      clarified. Adult chimpanzees showed the ability to trace a model, which was
      difficult for humans who had just started imitation. The second experiment, free
      drawing on incomplete facial stimuli, revealed the remarkable difference between
      two species. Humans (N = 57, 6-38 months) tend to complete the missing parts even
      with immature motor control, whereas chimpanzees never completed the missing
      parts and instead marked the existing parts or traced the outlines. Cognitive
      characteristics may affect the emergence of representational drawings. 

PMID- 25376269
TI  - Endocan: a new molecule playing a role in the development of hypertension and
      chronic kidney disease?
AB  - Recently, endocan-formerly known as endothelial cell-specific molecule 1 (ESM-1)-
      was found to be associated with entities such as cancer, hypertension, renal
      transplant rejection, and chronic renal failure. Endothelial cells of many organs
      secrete endocan, but the exact functions of this relatively new molecule have not
      been elucidated completely. Emerging evidence suggests, however, that endocan
      plays an important role in inflammation, upregulation of cell adhesion molecules,
      lymphocyte functions, and endothelial cytoskeleton rearrangement. As suggested
      above, endocan has a prognostic impact in hypertension, transplant rejection, and
      chronic renal failure. In the current review, the evidence regarding endocan,
      hypertension, and chronic renal failure are summarized.

PMID- 25376270
TI  - Short-, middle- and long-term safety of superparamagnetic iron oxide-labeled
      allogeneic bone marrow stromal cell transplantation in rat model of lacunar
      infarction.
AB  - Recently, both basic and clinical studies demonstrated that bone marrow stromal
      cell (BMSC) transplantation therapy can promote functional recovery of patients
      with CNS disorders. A non-invasive method for cell tracking using MRI and
      superparamagnetic iron oxide (SPIO)-based labeling agents has been applied to
      elucidate the behavior of transplanted cells. However, the long-term safety of
      SPIO-labeled BMSCs still remains unclear. The aim of this study was to
      investigate the short-, middle- and long-term safety of the SPIO-labeled
      allogeneic BMSC transplantation. For this purpose, BMSCs were isolated from
      transgenic rats expressing green fluorescent protein (GFP) and were labeled with
      SPIO. The Na/K ATPase pump inhibitor ouabain or vehicle was stereotactically
      injected into the right striatum of wild-type rats to induce a lacunar lesion (n
      = 22). Seven days after the insult, either BMSCs or SPIO solution were
      stereotactically injected into the left striatum. A 7.0-Tesla MRI was performed
      to serially monitor the behavior of BMSCs in the host brain. The animals were
      sacrificed after 7 days (n = 7), 6 weeks (n = 6) or 10 months (n = 9) after the
      transplantation. MRI demonstrated that BMSCs migrated to the damage area through
      the corpus callosum. Histological analysis showed that activated microglia were
      present around the bolus of donor cells 7 days after the allogeneic cell
      transplantation, although an immunosuppressive drug was administered. The SPIO
      labeled BMSCs resided and started to proliferate around the route of the cell
      transplantation. Within 6 weeks, large numbers of SPIO-labeled BMSCs reached the
      lacunar infarction area from the transplantation region through the corpus
      callosum. Some SPIO nanoparticles were phagocytized by microglia. After 10
      months, the number of SPIO-positive cells was lower compared with the 7-day and 6
      week groups. There was no tumorigenesis or severe injury observed in any of the
      animals. These findings suggest that BMSCs are safe after cell transplantation
      for the treatment of stroke. 

PMID- 25376271
TI  - Control of hypertension and survival in haemodialysis patients.
AB  - Hypertension is common in approximately 80% to 90% of patients at the start of
      dialysis therapy and is an established risk factor for cardiovascular disease.
      Therefore, it should be controlled, even in the chronic dialysis population.
      Observational studies indicate a U-shaped phenomenon, as the mortality rate is
      high among those with hypertension as well as those with hypotension. Among
      chronic dialysis patients, randomized controlled trials on the effect of anti
      hypertensive treatment are not conclusive, at least not as demonstrated by
      studies with a large sample size. Similar to other potentially effective drug
      therapies such as erythropoietin stimulating agent, statins, and uraemic toxin
      adsorbents, the benefit of anti-hypertensive treatment remains to be demonstrated
      in dialysis patients. The blood pressure target level, however, is difficult to
      determine as evidence for the level of appropriate target is lacking. Currently,
      it should be determined individually, as the priority is to perform haemodialysis
      as prescribed. The target levels of blood pressure for chronic haemodialysis
      patients are not stated except in the Guidelines in the Japanese Society for
      Dialysis Therapy. In this guideline, systolic blood pressure between 140 to 159
      mmHg is preferable among elderly patients with comorbid conditions. Rapid
      ultrafiltration, such as >600 mL/h, is to be avoided. Intra-dialysis hypotension,
      muscle cramps, and other complaints during HD are preventable. Moreover, the
      nutritional status should be maintained within the normal range with adequate
      intake of protein and calories, but with salt restriction. Further studies are
      necessary for better management of hypertension in the dialysis population. 

PMID- 25376272
TI  - Proton beam therapy for unresectable intrahepatic cholangiocarcinoma.
AB  - BACKGROUND AND AIM: Treatment for unresectable intrahepatic cholangiocarcinoma
      (ICC) has not been established. The aim of the study was to evaluate the outcome
      of proton beam therapy (PBT) for patients with unresectable ICC. METHODS: Up to
      2010, 20 patients (11 males, 9 females, median age 63 years old) with
      unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV,
      respectively) were treated with PBT. The largest dimensions of the tumors ranged
      from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes
      received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17
      fractions, respectively. Four patients received concurrent chemotherapy (tegafur,
      gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated
      curatively, and eight were treated palliatively because tumors were present
      outside the irradiation field. RESULTS: In the curative group, nine tumors within
      the irradiated field were controlled in follow-up of 8.6-62.6 months (median:
      20.8 months). Median survival rates in the curative and palliative groups were
      27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were
      82% and 38%, and 50% and 0%, respectively. Eight patients survived for > 2 years,
      and there was no distant metastasis in five of these patients after 2 years. No
      severe side-effects occurred. CONCLUSIONS: The results suggest that long-term
      survival can be achieved using PBT for patients with unresectable ICC without
      distant metastasis. Further studies are required to determine the optimal
      treatment schedule and best combination of PBT and chemotherapy.

PMID- 25376274
TI  - Modular tumor endoprostheses in surgical palliation of long-bone metastases: a
      reduction in tumor burden and a durable reconstruction.
AB  - BACKGROUND: Surgical treatment of bone metastases has become increasingly
      important as patients live longer with metastatic cancer and one of the main aims
      is a long-lasting reconstruction which survives the patient. Conventional
      osteosynthesis may not be able to achieve this objective in the context of modern
      day cancer care. METHODS: This study evaluates the oncological outcomes,
      treatment-related complications, and function after resection of metastases and
      reconstruction with modular tumor endoprostheses in 80 patients. All patients who
      underwent surgical treatment with modular tumor prostheses for bone metastases
      from 1993 to 2008 were traced by our tumor database and clinical information was
      recorded from patient case. RESULTS: Mean age was 63 years. The most common
      primary tumors were renal cell (47%), breast (21%), and lung (8%). The proximal
      femur was affected in 45%, proximal humerus in 26%, and the distal femur in 17%
      of cases. In 22 cases, the tumor prosthesis was implanted during a revision
      operation. Mean overall survival after surgery was 2.9 years. Overall survival
      rate was 70% at one year and 20% at five years. Implant survival was 83% after
      one year and 74% at five years. Overall rate of operative revision was 18%.
      CONCLUSIONS: Our data collectively suggest that despite higher costs,
      implantation of modular tumor endoprostheses may be a suitable treatment for bone
      metastases with a low complication rate and rapid improvement in function in
      appropriately selected patients.

PMID- 25376275
TI  - G-patch domain containing 2, a gene highly expressed in testes, inhibits nuclear
      factor-kappaB and cell proliferation.
AB  - G-patch domain containing 2 (GPATC2), a human gene that is highly expressed in
      the testes, was implicated as a novel cancer/testis antigen. The present study
      investigated GPATC2 expression in a number of human cell lines and rat tissues,
      and its potential biological function in 293T cells. Semi-quantitative reverse
      transcription-polymerase chain reaction analysis showed that GPATC2 was widely
      expressed in 15 human cell lines (representing different lineages) and in 11
      different rat tissues, and that the GPATC2 mRNA relative expression level was
      significantly higher in the testis than it was in other tissues. 293T cells were
      transiently transfected with GPATC2-p enhanced green fluorescent protein (EGFP)
      N1 or GPATC2-pEGFP-C3 and the nuclei were stained with 4',6'-diamidino-2
      phenylindole. The results showed that GPATC2 is predominantly expressed in the
      nucleus of 293T cells. Overexpression of GPATC2 may inhibit transcription of the
      NF-kappaB reporter gene. The role of GPATC2 in proliferation was analyzed with
      cell counting kit-8, colony-forming efficiency and flow cytometry assays. The
      results indicated that over-expression of GPATC2 in 293T cells significantly
      inhibited cell proliferation by decreasing the number of cells in S phase. By
      contrast, GPATC2 knockdown by RNA interference exhibited the opposite effect,
      suggesting that GPATC2 may be involved in inhibiting G1-S phase transition in
      293T cells. In conclusion, these results provide novel insight into the breadth
      of expression of GPATC2 and its role in cell proliferation.

PMID- 25376276
TI  - Who uses NHS Direct? Investigating the impact of ethnicity on the uptake of
      telephone based healthcare.
AB  - INTRODUCTION: NHS Direct, a leading telephone healthcare provider worldwide,
      provided 24/7 health care advice and information to the public in England and
      Wales (1998-2014). The fundamental aim of this service was to increase
      accessibility, however, research has suggested a disparity in the utilisation of
      this service related to ethnicity. This research presents the first national
      study to determine how the diverse population in England have engaged with this
      service. METHODS: NHS Direct call data from the combined months of July, 2010
      October, 2010, January 2011 and April, 2011 was analysed (N = 1,342, 245) for all
      0845 4647 NHS Direct core service calls in England. Expected usage of NHS Direct
      was determined for each ethnic group of the population by age and gender and
      compared by actual usage using Chi-square analysis. A one-way analysis of
      variance (ANOVA) was used to determine variations of uptake by ethnic group and
      Index for Multiple Deprivation (IMD) 2010 rank. RESULTS: Results confirmed that
      all mixed ethnic groups (White and Black Caribbean, White and Black African,
      White and Asian) had a higher than expected uptake of NHS Direct which held
      consistent across all age groups. Lower than expected uptake was found for Black
      (African/Caribbean) and Asian (Bangladeshi/Indian/Chinese) ethnic group which
      held consistent by age and gender. For the Pakistani ethnic group usage was
      higher than expected in adults aged 40 years and older although was lower than
      expected in younger age groups (0-39). CONCLUSION: Findings support previous
      research suggesting a variation in usage of NHS Direct influenced by ethnicity,
      which is evidenced on a national level. Further research is now required to
      examine the underlying barriers that contribute to the ethnic variation in uptake
      of this service.

PMID- 25376277
TI  - Design and photovoltaic characterization of dithieno[3,2-b:2',3'-d]silole
      copolymers with positioning phenyl groups.
AB  - A two-dimensional (2D) low bandgap polymer () based on dithieno[3,2-b:2',3'
      d]silole (DTS) with phenyl substitution on the bridging silicon atom and
      thiazolo[5,4-d]thiazole (TTz) was designed and synthesized for photovoltaic
      applications. The impact of conjugated side chains on the optical,
      electrochemical and energy levels of the polymer was studied. The phenyl
      substituted DTS polymer exhibited a 0.16 eV down-shifted highest occupied
      molecular orbital (HOMO) energy level and ca. 0.1 eV narrowed bandgap in
      comparison to the corresponding polymers with alkyl substitution on the silicon
      bridge. The influence of the blend weight ratio, the PFN layer, mixed solvent,
      THF exposure and polar solvent treatment and thermal annealing on the performance
      of :PC71BM devices was studied.  : PC71BM (1 : 1, weight ratio) devices delivered
      the highest power conversion efficiency of 2.14% by using the PFN layer and THF
      annealing. Thermal annealing was found to exert a negative effect on the device
      performance. The morphology evolution of blend films processed with different
      solvents explained the difference in device performance. The results indicate
      that phenyl substitution is an effective way to tune the HOMO and bandgap of
      polymer donors for enhanced photovoltaic performance with the as-demonstrated 2D
      conjugated DTS structure. 

PMID- 25376279
TI  - Review of the prevalence and drug resistance of tuberculosis in prisons: a hidden
      epidemic.
AB  - SUMMARY The prison setting has been often cited as a possible reservoir of
      tuberculosis (TB) including multidrug-resistant (MDR)-TB. This is particularly
      true in low-income, high TB prevalence countries in Sub-Saharan Africa. A
      systemic literature review was done to assess the prevalence, drug resistance and
      risk factors for acquiring TB in the prison population. Our review indicated a
      high prevalence of TB in prisons which is reported to be 3- to 1000-fold higher
      than that found in the civilian population, indicating evidence and the need for
      public health policy formulation. In addition, high levels of MDR and extensively
      drug-resistant (XDR)-TB have been reported from prisons, which is a warning call
      to review prison TB control strategy. Multiple risk factors such as overcrowding,
      poor ventilation, malnutrition, human immunodeficiency virus (HIV), and others
      have fuelled the spread of TB in prisons. Furthermore, the impact extends beyond
      the prison walls; it affects the civilian population, because family visits,
      prison staff, and members of the judiciary system could be potential portals of
      exit for TB transmission. The health of prisoners is a neglected political and
      scientific issue. Within these background conditions, it is suggested that
      political leaders and scientific communities should work together and give
      special attention to the control of TB and MDR-TB in prisons. If not, TB in
      prisons will remain a neglected global problem and threatens national and
      international TB control programmes. Further researches are required on the
      prevalence and drug resistance of smear-negative TB in prisons. In addition,
      evidence of the circulating strains and transmission dynamics inside prisons is
      also warranted. 

PMID- 25376278
TI  - Establishment of macrocyclic lactone resistant Dirofilaria immitis isolates in
      experimentally infected laboratory dogs.
AB  - BACKGROUND: Strains of Dirofilaria immitis suspected of lack of efficacy (LOE) to
      macrocyclic lactone (ML) preventive drugs have been increasingly reported in dogs
      by practicing veterinarians since 2005 in the Lower Mississippi Delta region. If
      proven, and not controlled in the early stages, the emergence of ML drug
      resistance threatens to become a widespread problem in the US that may limit the
      effectiveness of current preventive drug treatment methods. METHODS: To validate
      practice reports, a statewide survey of Louisiana veterinarians was done to
      define the extent of the problem and identify focal 'hotspots' of reported ML
      LOEs using Geographic Information Systems (GIS) methods. The present study then
      utilized microfilariae (Mf) from two canine field cases from different state
      locations that fit criteria for a high index of suspicion of LOE against
      heartworms by ML drugs. Blood containing Mf from the canine field cases was used
      to infect and produce L3 in Aedes aegypti for experimental infection of two
      groups of dogs, each of which contained two laboratory dogs, one treated with
      prophylactic ivermectin (12 MUg/kg) monthly for 6 months at twice the label dose
      (6 MUg/kg), and one untreated control. RESULTS: Both treated and untreated dogs
      from Group I and Group II developed patent D. immitis infections by 218 DPI and
      189 DPI, respectively, as evidenced by a positive occult heartworm antigen test
      and microfilaremia by the Knott's test. Mf counts gradually increased post
      patency in test and control dogs. Infective larvae raised from microfilariae from
      the treated Group I dog were used to successfully establish a second generation
      isolate, confirming heritability of resistance in the face of a monthly
      ivermectin challenge dose of 24 MUg/kg, given monthly for 3 months. CONCLUSIONS:
      These experimental infection studies provide in vivo evidence of the existence of
      ML drug resistance in dogs infected by D. immitis L3 from suspect field LOE cases
      in the Lower Mississippi Delta. Results encourage further work on mechanisms
      underlying the emergence of ML resistance in D. immitis and development of
      evidence-based resistance management strategies for heartworm preventives in
      order to extend the useful life of current drugs.

PMID- 25376280
TI  - Emerging strategies for the management of hepatocellular carcinoma.

PMID- 25376281
TI  - Genome-wide profiling of DNA methylation and tumor progression in human
      hepatocellular carcinoma.
AB  - OBJECTIVE: To clarify the progression pattern of abnormal DNA methylation during
      the development of hepatocellular carcinoma (HCC) using a comprehensive
      methylation assay. METHODS: We used an Infinium HumanMethylation450 BeadChip
      array that can analyze >485,000 CpG sites distributed throughout the genome for a
      comprehensive methylation study of 117 liver tissues consisting of 59 HCC and 58
      noncancerous livers. Altered DNA methylation patterns during tumor progression
      were also analyzed. RESULTS: We identified 38,330 CpG sites with significant
      differences in methylation levels between HCCs and noncancerous livers (DM-CpGs)
      using strict criteria. Of the DM-CpGs, 92% were hypomethylated and only 3,051
      CpGs (8%) were hypermethylated in HCC. The DM-CpGs were more prevalent within
      intergenic regions with isolated CpGs. In contrast, DM-CpGs that were
      hypermethylated in HCC were predominantly located within promoter regions and CpG
      islands (p < 0.0001). The association between methylation profiles of DM-CpGs and
      tumor size was statistically significant, especially in hepatitis C virus (HCV)
      positive cases (p = 0.0001). CONCLUSIONS: We clarified the unique characteristics
      of DM-CpGs in human HCCs. The stepwise progression of alterations in DNA
      methylation was a common feature of HCV-related hepatocarcinogenesis.

PMID- 25376282
TI  - Epidemiological trends of hepatocellular carcinoma in Austria.
AB  - BACKGROUND/AIMS: The heterogeneous epidemiology of hepatocellular carcinoma (HCC)
      with the highest incidence rates in East Asia, sub-Saharan Africa and Melanesia
      results from variations in the main risk factors. We investigated epidemiological
      trends, including incidence and mortality, of patients diagnosed with HCC over a
      20-year period in Austria. METHODS: Data on age-adjusted incidence rates of HCC
      were obtained from the Austrian National Cancer Registry, which compiles
      nationwide data on all newly diagnosed cancers. Data on age-adjusted mortality
      were obtained from the national death registry (Statistics Austria). RESULTS: Of
      24,939 patients diagnosed with hepatobiliary tumors between 1990 and 2009, 8,561
      subjects had HCC (m/f ratio 75/25%; mean age 69 years). Lymph node and distant
      metastases were present in 7.5 and 12.2%, respectively. The age-adjusted
      incidence rate was significantly higher in men than women (m/f ratio 4.5/1) and
      markedly increased in men (4.68/5.10) but remained stable in women (1.18/1.11).
      Similarly, the age-adjusted mortality rate was significantly higher in men than
      women (m/f ratio 4.5/1), increased in men (4.02/4.98) and remained stable in
      women (0.92/1.0). The median overall survival was 4.5 months for men and 3.2
      months for women with 1-/5-year survival rates of 33/11% and 28/10%,
      respectively. CONCLUSION: HCC is the most common hepatobiliary neoplasia in
      Austria and has a very poor prognosis. The age-adjusted incidence and mortality
      rates were higher in males, increased over time in men and remained stable in
      women. Extrahepatic metastases were rarely diagnosed and associated with dismal
      survival.

PMID- 25376283
TI  - Radiofrequency ablation for hepatocellular carcinoma measuring 2 cm or smaller:
      results and risk factors for local recurrence.
AB  - OBJECTIVE: The purpose of this study was to evaluate the risk factors for local
      recurrence with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC)
      measuring <=2 cm. METHODS: This study involved 234 patients with 274 HCCs
      measuring <=2 cm who had undergone RFA as the initial treatment. The mean tumor
      diameter was 1.478 cm. The median follow-up period was 829 days. We evaluated the
      post-RFA cumulative local recurrence rate and analyzed the risk factors
      contributing to clinical outcomes. RESULTS: Cumulative local recurrence rates
      were 9, 19 and 19% at 1, 2 and 3 years, respectively. Among the 145 cases with a
      complete safety margin (SM) after RFA, only 4 developed local tumor recurrence
      and the cumulative rates of local tumor recurrence at 1, 2 and 3 years were 2, 3
      and 3%, respectively. Among the 129 cases with incomplete SM, local tumor
      recurrence developed in 34 and the cumulative rates of local tumor progression at
      1, 2 and 3 years were 14, 36 and 36%, respectively. In multivariate analysis,
      significant risk factors were tumor location (liver surface), irregular gross
      type and SM <5 mm. CONCLUSION: Even with HCC measuring <=2 cm, location and gross
      type of tumor should be carefully evaluated before RFA is performed.

PMID- 25376284
TI  - Non-hypervascular hypointense nodules >=1 cm on the hepatobiliary phase of
      gadoxetic acid-enhanced magnetic resonance imaging in cirrhotic livers.
AB  - OBJECTIVE: To determine the pathologic nature of non-hypervascular hypointense
      nodules (>=1 cm) on the hepatobiliary phase (HBP) of gadoxetic acid-enhanced
      magnetic resonance (MR) imaging and to describe the chronological changes of
      their imaging features on follow-up MR imaging. PATIENTS AND METHODS: This
      retrospective study was approved by our Institutional Review Board and the
      requirement for informed consent was waived. 69 patients with 115 non
      hypervascular HBP hypointense nodules (>=1 cm in diameter) in cirrhotic livers
      were enrolled. 67 nodules were histologically diagnosed (group 1) and 52 nodules
      were followed up with MR for at least 12 months (group 2); 4 nodules belonged to
      both groups. Two radiologists reviewed the initial and follow-up MR images to
      determine the size and signal intensities on unenhanced T1- and T2-weighted
      images, dynamic phases and HBP images in consensus. In addition, two pathologists
      reviewed the histologic findings including H&E staining and four kinds of
      immunohistochemical staining in group 1. RESULTS: In group 1, 73.1% (49/67) of
      nodules were hepatocellular carcinomas. In group 2, 32.7% (17/52) of nodules
      developed arterial hypervascularity on follow-up, and 78.8% (41/52) showed at
      least one of the three imaging features considered to indicate malignant changes
      during follow-up (mean 19 +/- 10 months): increase in diameter by >=5 mm (23/52,
      44.2%), arterialization (17/52, 32.7%) and hyperintensity on T2-weighted images
      (18/52, 34.6%). CONCLUSION: Our study results demonstrate that a significant
      proportion of non-hypervascular HBP hypointense nodules (>=1 cm in diameter) in
      patients with cirrhosis showed either malignant features on pathology (73.1%) or
      developed hypervascularity (32.7%) during follow-up.

PMID- 25376285
TI  - Ultrasound fusion imaging of hepatocellular carcinoma: a review of current
      evidence.
AB  - With advances in technology, imaging techniques that entail fusion of sonography
      and CT or MRI have been introduced in clinical practice. Ultrasound fusion
      imaging provides CT or MRI cross-sectional multiplanar images that correspond to
      the sonographic images, and fusion imaging of B-mode sonography and CT or MRI can
      be displayed simultaneously and in real time according to the angle of the
      transducer. Ultrasound fusion imaging helps us understand the three-dimensional
      relationship between the liver vasculature and tumors, and can detect small liver
      tumors with poor conspicuity. This fusion imaging is attracting the attention of
      operators who perform radiofrequency ablation (RFA) for the treatment of hepatic
      malignancies because this real-time, multimodality comparison can increase
      monitoring and targeting confidence during the procedure. When RFA with fusion
      imaging was performed on small hepatocellular carcinomas (HCCs) with poor
      conspicuity, it was reported that the rates of technical success and local tumor
      progression were 94.4-100% and 0-8.3%. However, there have been no studies
      comparing fusion imaging guidance and contrast-enhanced sonography, CT or MRI
      guidance in ablation. Fusion imaging-guided RFA has proved to be effective for
      HCCs that are poorly defined on not only conventional B-mode sonography but also
      contrast-enhanced sonography. In addition, fusion imaging could be useful to
      assess the treatment response of RFA because of three-dimensional information.
      Here, we give an overview of the current status of ultrasound fusion imaging for
      clinical application in the liver.

PMID- 25376286
TI  - Focal lesions in the cirrhotic liver: their pivotal role in gadoxetic acid
      enhanced MRI and recognition by the Western guidelines.
AB  - Hepatocellular carcinoma (HCC) is a major health concern, and early HCC diagnosis
      is a primary radiological concern. The goal of imaging liver cirrhosis is the
      early identification of high-grade dysplastic nodules/early HCC since their
      treatment is associated with a higher chance of radical cure and lower recurrence
      rates. The newly introduced MRI contrast agent gadoxetic acid (gadolinium
      ethoxybenzyl-diethylenetriamine pentaacetic acid, Gd-EOB-DTPA) has enabled the
      concurrent assessment of tumor vascularity and hepatocyte-specific contrast
      enhancement during the hepatobiliary phase (HBP), which can help to detect and
      characterize smaller HCCs and their precursors. HBP-EOB-MRI identifies
      hypovascular HCC nodules that are difficult to detect using ultrasonography or
      computed tomography, which do not show the diagnostic HCC hallmarks of arterial
      washin and portal/delayed washout. During the HBP, typical HCC and early HCC
      appear hypointense on EOB-MRI, whereas low-grade dysplastic or regenerative
      nodules appear as iso- or hyperintense lesions. The diagnostic accuracy of EOB
      MRI for the diagnosis of early HCC is approximately 95-100%. One third of
      hypovascular hypointense nodules in HBP become hypervascular 'progressed' HCC,
      with a 1- and 3-year cumulative incidence of 25 and 41%, respectively. Therefore,
      these hypovascular nodules should be strictly followed up or definitely treated
      as typical HCC. Due to this capability of identifying the precursors and
      biological behavior of HCC, EOB-MRI has rapidly become a key imaging tool for the
      diagnosis of HCC and its precursors, despite the scarce MRI availability
      throughout Europe. With increasing experience, EOB-MRI may eventually be
      established as the diagnostic imaging modality of choice in this setting. Full
      recognition by the Western EASL-AASLD guidelines is expected.

PMID- 25376287
TI  - Duration of stable disease is associated with overall survival in patients with
      advanced hepatocellular carcinoma treated with sorafenib.
AB  - BACKGROUND: Sorafenib is a molecular-targeting agent showing improved overall
      survival (OS) for advanced hepatocellular carcinoma (HCC). Although tumor
      dormancy, characterized by stable tumor status or stable disease (SD) without
      tumor regression, is a unique feature of sorafenib treatment, the contribution of
      SD to OS remains debatable. This study aimed to clarify the correlation between
      SD periods and OS in patients with HCC treated with sorafenib. METHODS: From May
      2009 to January 2013, 269 patients with advanced-stage HCC were treated with
      sorafenib at the Kinki University Hospital. The antitumor response of sorafenib
      was evaluated in 158 patients using the modified Response Evaluation Criteria in
      Solid Tumors, and patients with SD were divided into two subgroups according to
      the median duration of SD: short SD (<3 months) and long SD (>=3 months). The
      relationship between the duration of SD and OS was analyzed among patients with
      complete (CR) and partial response (PR), and long and short SD using the Kaplan
      Meier method. RESULTS: The median OS was 5.7 months in the short SD, 20.8 months
      in the long SD and 17.9 months in the CR + PR group. Although the duration of OS
      was significantly longer in the long SD group than the short SD group, no
      difference in OS was detected between the patients with CR + PR and patients with
      long SD. The impact of long SD on OS could be as strong as that of CR + PR.
      CONCLUSION: Achievement of long SD is one of the important goals for improving
      survival in patients with HCC treated with sorafenib.

PMID- 25376288
TI  - The ART score is not effective to select patients for transarterial
      chemoembolization retreatment in an Italian series.
AB  - BACKGROUND: The ART score (a point score for the assessment of retreatment with
      transarterial chemoembolization, TACE) has been recently developed in Austria to
      differentiate patients who may benefit from multiple sessions of TACE for
      hepatocellular carcinoma (HCC) treatment. The primary aim of the study was to
      test the validity of the ART score in an Italian study cohort. The secondary aims
      were to evaluate overall survival (OS) and clinical determinants of improved
      survival in patients treated with multiple TACE sessions. METHODS: The ART score
      and the clinical outcome of 51 consecutive patients with HCC submitted to
      multiple TACE sessions from April 2002 to December 2009 were retrospectively
      analyzed. RESULTS: Median OS was 26.0 months (95% confidence interval 18.4-33.6)
      with 1-, 3- and 5-year survival rates of 75, 33 and 11%, respectively). Thirty
      three patients had an ART score of 0-1.5 and in 18 it was >=2.5, but in our
      patient series, the ART score was not found to be a predictor of survival (p =
      0.173). At univariate analysis, tumor extent (uni- vs. bilobar: 34.0 vs. 9.0
      months; p < 0.001), Child-Pugh score before the second TACE (A vs. B7 vs. B8-9:
      26.0 vs. 16.0 vs. 5.0 months; p = 0.005) and Child-Pugh score increase between
      the first and second TACE (absent vs. + 1 point vs. + >=2 points: 27.0 vs. 4.0
      vs. 5.0 months; p < 0.001) were statistically related with survival. At
      multivariate analysis, only Child-Pugh score increase remained a significant
      predictor of worse survival (p = 0.001, hazard rate = 11.6). CONCLUSIONS: The ART
      score was not found to work as an objective tool to guide TACE retreatment in our
      Italian patient series, only the Child-Pugh score increase was an independent
      predictor of a shorter survival.

PMID- 25376290
TI  - Prognostic values of vascular endothelial growth factor and matrix
      metalloproteinase-2 in hepatocellular carcinoma after radiotherapy.
AB  - OBJECTIVES: Hepatocellular carcinoma (HCC) is a highly vascularized tumor. In
      this study, we investigated the prognostic and predictive values of proangiogenic
      factors in HCC patients receiving radiotherapy. METHODS: Between September 2008
      and December 2009, a total of 50 patients treated with radiotherapy were
      prospectively enrolled in this study. Serum and urine samples were collected <1
      week before and after radiotherapy. RESULTS: After completion of radiotherapy,
      serum vascular endothelial growth factor (VEGF)/platelet (Plt) levels were
      significantly increased (p < 0.01). Patients who experienced hepatic tumor
      recurrence outside the radiation field showed higher VEGF-A/Plt levels before and
      after radiotherapy than patients who did not (p = 0.04), whereas patients who had
      hepatic tumor recurrence inside the radiation field showed significantly higher
      matrix metalloproteinase (MMP)-2 levels after radiotherapy (p = 0.04). On
      multivariate analyses, a high level of either VEGF/Plt or MMP-2 (>=median) before
      radiotherapy was a significant independent prognostic factor for a worse
      progression-free survival (p = 0.04). CONCLUSIONS: In HCC patients receiving
      radiotherapy, levels of VEGF/Plt and MMP-2 before radiotherapy can be useful to
      predict treatment outcome. This study also suggests the necessity of anti
      angiogenic therapy, such as sorafenib, since radiotherapy increases VEGF/Plt
      levels, and higher levels of VEGF/Plt are associated with a poor outcome.

PMID- 25376289
TI  - Validation of three staging systems for hepatocellular carcinoma (JIS score,
      biomarker-combined JIS score and BCLC system) in 4,649 cases from a Japanese
      nationwide survey.
AB  - OBJECTIVE: Clinical staging is very important for optimal therapeutic strategy
      and prognostic prediction in patients with hepatocellular carcinoma (HCC). The
      Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used and
      best-validated method for HCC. Similarly, the conventional Japan Integrated
      Staging (c-JIS) score and the biomarker-combined JIS (bm-JIS) score have also
      been reported to effectively stratify HCC patients. The aim of this study was to
      evaluate the performance of these three staging systems for prognostic
      prediction. METHODS: A total of 4,649 HCC patients were included in this study. A
      multivariate analysis identified the independent risk factors associated with
      overall survival. The stratification ability and the suitability as a prognostic
      model of the three staging systems were compared. RESULTS: Multivariate analysis
      revealed that male sex, higher Child-Pugh score, tumor size >2.0 cm, multiple
      tumors, vascular invasion, higher alpha-fetoprotein (AFP) level, higher des-gamma
      carboxyprothrombin level, higher Lens culinaris agglutinin-reactive AFP level,
      and a performance status of 3-4 were independent risk factors in HCC. The
      independent homogenizing ability and stratification value of the bm-JIS score
      were higher than those of the c-JIS score and the BCLC system (chi(2) = 972.7581,
      758.1041 and 679.6832, respectively). Moreover, the bm-JIS score had the lowest
      Akaike Information Criteria value, followed by the c-JIS score and the BCLC
      system (9,844.278, 10,054.93 and 10,131.35, respectively). CONCLUSIONS: Our
      results suggest that the bm-JIS score offers good stratification ability and is a
      better prognostic predictor than the c-JIS score and the BCLC system.

PMID- 25376291
TI  - Decreased blood flow after sorafenib administration is an imaging biomarker to
      predict overall survival in patients with advanced hepatocellular carcinoma.
AB  - BACKGROUND: Sorafenib is a multikinase inhibitor targeting Raf and protein
      tyrosine kinases, which are involved in cell growth and tumor angiogenesis.
      Sorafenib administration induces temporary inhibition of tumor growth and a
      decrease in arterial blood flow in a considerable number of hepatocellular
      carcinoma (HCC) patients. We retrospectively evaluated the association between
      decreased blood flow and the overall survival (OS) of HCC patients after the
      initiation of sorafenib therapy. PATIENTS AND METHODS: Therapeutic responses of
      158 advanced HCC patients with hypervascular tumors who had received sorafenib
      for more than 1 month were analyzed. To assess their therapeutic response,
      patients underwent radiological evaluation before and every 4-6 weeks after the
      initiation of sorafenib treatment. After the classification of patients into
      three groups based on the change in arterial enhancement during treatment (no
      change, decrease and disappearance), the OS of each group was compared using the
      Kaplan-Meier method. RESULTS: Statistically significant differences in OS were
      observed among the three groups (p < 0.001). A decrease or disappearance of
      arterial enhancement was significantly associated with improved OS compared to
      patients with no change in arterial enhancement; the median OS was 19.9 months
      (95% confidence interval, CI, 16.4-24.5 months) and 6.0 months (95% CI, 4.0-8.8
      months), respectively (p < 0.001). However, there was no difference in OS between
      the decrease and disappearance groups (p = 0.88). CONCLUSION: We conclude that
      decreased arterial enhancement during sorafenib treatment was associated with the
      longest OS and could therefore reflect an effective response.

PMID- 25376292
TI  - Identification of epigenetically inactivated genes in human hepatocellular
      carcinoma by integrative analyses of methylation profiling and pharmacological
      unmasking.
AB  - OBJECTIVES: DNA methylation-dependent transcriptional inactivation of tumor
      suppressor genes (TSGs) is critical for the pathogenesis of hepatocellular
      carcinoma (HCC). This study identifies potential TSGs in HCCs using methylation
      profiling and pharmacological unmasking of methylated TSGs. METHODS: Methylation
      profiling was performed on 22 pairs of HCCs and their corresponding noncancerous
      liver tissues using the Infinium HumanMethylation27 BeadChip. We also determined
      the gene reexpression after treatment with 5-aza-2'-deoxycytidine (5-Aza-dC) and
      trichostatin A (TSA) in 5 HCC cell lines. RESULTS: We selected CpGs that
      exhibited a significant increase in methylation in HCC tissues compared with that
      of the noncancerous control group. Two hundred and thirteen CpGs on different
      gene promoters with a mean difference in the beta value >=0.15 and a value of p <
      0.05 were selected. Of the 213 genes, 45 genes were upregulated in 3 or more HCC
      cell lines with multiplier value of differences >=2.0 after 5-Aza-dC and TSA
      treatment. CONCLUSIONS: We identified several potential TSGs that participate in
      transcription inactivation through epigenetic interactions in HCC. The results of
      this study are important for the understanding of functionally important
      epigenetic alterations in HCC.

PMID- 25376293
TI  - Adjuvant therapy for hepatocellular carcinoma after curative treatment.
AB  - Hepatocellular carcinoma (HCC) is a common malignancy in the world. Although
      resection and various locoregional therapies can achieve eradication or complete
      ablation of small HCC, HCC recurrence after these therapies is still common.
      Although candidates for medical ablation usually exhibit compensated hepatic
      functional status, the frequent recurrence of HCC after successful ablation
      contributes to short survival. Therefore, attempts to prevent HCC recurrence are
      essential to prolong survival. Efforts in preventing HCC recurrence after
      curative therapies include prevention of early recurrence by improving liver
      immunity and eliminating microscopic tumor foci or micrometastases, and
      prevention of late recurrence by reducing the hepatitis activity and using
      antiviral therapies based on viral suppression/eradication. In HCC with vascular
      invasion, adjuvant transcatheter arterial chemoembolization should be considered
      to provide better control. Whether the adjuvant use of sorafenib may suppress
      microscopic tumor foci or micrometastases may be unveiled in the near future.
      This review article will update the algorithms, novel medication or study drugs
      in the prevention of HCC after curative therapies.

PMID- 25376294
TI  - Considerations for radiation therapy in hepatocellular carcinoma: the radiation
      oncologists' perspective.
AB  - Although the Barcelona Clinic Liver Cancer staging system does not recommend
      radiation therapy (RT) as a locoregional modality in hepatocellular carcinoma
      (HCC), many prospective and retrospective studies have reported excellent local
      control with favorable survival rates after RT using modern techniques.
      Additionally, there have been several comparative or meta-analysis results
      reporting the superiority of RT in unresectable HCC. Therefore, it might be more
      reasonable to apply RT in unresectable HCC as an alternative locoregional
      modality to improve local control in HCC. However, several considerations for the
      application of RT in HCC exist. The considerations for RT in HCC are purpose,
      combination treatment and technique. The purpose of RT should be based on
      baseline liver status as well as tumor extent and location. There are several
      reasonable advantages in local, intrahepatic and extrahepatic control when
      combined with other modalities, but it could lead to overtreatment in some cases.
      The technical considerations according to the purpose and combination modality
      are the final step. For the application of RT in HCC, the purpose of RT,
      combination strategy and technical considerations should be taken into account.

PMID- 25376295
TI  - 2014 KLCSG-NCC Korea Practice Guidelines for the management of hepatocellular
      carcinoma: HCC diagnostic algorithm.
AB  - Hepatocellular carcinoma (HCC) is the fifth most commonly occurring cancer in
      Korea and typically has a poor prognosis with a 5-year survival rate of only
      28.6%. Therefore, it is of paramount importance to achieve the earliest possible
      diagnosis of HCC and to recommend the most up-to-date optimal treatment strategy
      in order to increase the survival rate of patients who develop this disease.
      After the establishment of the Korean Liver Cancer Study Group (KLCSG) and the
      National Cancer Center (NCC), Korea jointly produced for the first time the
      Clinical Practice Guidelines for HCC in 2003, revised them in 2009, and published
      the newest revision of the guidelines in 2014, including changes in the
      diagnostic criteria of HCC and incorporating the most recent medical advances
      over the past 5 years. In this review, we will address the noninvasive diagnostic
      criteria and diagnostic algorithm of HCC included in the newly established KLCSG
      NCC guidelines in 2014, and review the differences in the criteria for a
      diagnosis of HCC between the KLCSG-NCC guidelines and the most recent imaging
      guidelines endorsed by the European Organisation for Research and Treatment of
      Cancer (EORTC), the Liver Imaging Reporting and Data System (LI-RADS), the Organ
      Procurement and Transplantation Network (OPTN) system, the Asian Pacific
      Association for the Study of the Liver (APASL) and the Japan Society of
      Hepatology (JSH).

PMID- 25376296
TI  - Hepatocellular carcinomas expressing 'stemness'-related markers:
      clinicopathological characteristics.
AB  - Hepatocellular carcinoma (HCC) is heterogeneous in histopathology, pathogenesis
      and biological behavior. There is accumulating evidence that the expression of
      'stemness'-related markers such as K19, EpCAM and CD133 in HCC is associated with
      an aggressive biological behavior and poor clinical outcome compared to
      conventional HCCs that do not express stemness-related markers. Compared to
      conventional HCCs, these tumors more frequently demonstrate infiltrative growth
      patterns, vascular invasion and more intratumoral fibrous stroma, and there is a
      spectrum of morphological and immunophenotypic features between HCCs with
      stemness-related marker expression, scirrhous HCCs and combined hepatocellular
      cholangiocarcinoma with stem cell features. Clinically, HCCs with stemness
      related marker expression are associated with increased serum alpha-fetoprotein
      levels and a poor prognosis, and are also beginning to be noticed radiologically.
      These tumors have also been recognized as a specific subtype in recent molecular
      classifications, and increasing interest in the molecular pathogenesis of HCCs
      with stemness-related marker expression will shed light on the development of
      targeted therapy for these tumors. Therefore, it is important that pathologists
      identify HCCs expressing stemness-related markers such as K19 during routine
      pathological evaluation of surgically resected or biopsied HCC tissue, as it will
      help to identify a high-risk subgroup of HCCs characterized by increased
      chemoresistance, earlier recurrence after surgical and/or locoregional treatment,
      increased invasiveness/metastasis and poor overall survival. We will discuss the
      clinicopathological characteristics of a HCC subtype expressing stemness-related
      markers and its future perspectives.

PMID- 25376297
TI  - Clinical features of vascular disorders associated with chronic hepatitis virus
      infection.
AB  - Hepatitis virus infections can be accompanied by extrahepatic manifestations that
      may be caused by the host's immune reaction to the viral infection. Vascular
      involvement is one of these manifestations and is occasionally associated with
      life-threatening conditions due to systemic organ failure. The unique profile of
      hepatitis-related vascular involvement is associated with infection by different
      types of hepatitis viruses. For example, polyarteritis nodosa is more frequently
      reported in patients with chronic hepatitis B than those with chronic hepatitis
      C. Similarly, membranous nephropathy is a notable manifestation among hepatitis B
      virus-positive patients. In contrast, patients infected with hepatitis C virus
      are at risk for cryoglobulinemia and membranoproliferative glomerulonephritis.
      Antiviral therapy is necessary to control these kinds of vasculitis related to
      hepatitis virus infections; however, immunosuppressive agents may be required to
      treat severe cases. New antiviral drugs for viral hepatitis could improve the
      prognosis of vascular and renal involvement.

PMID- 25376298
TI  - Accuracy of real-time tissue elastography for the evaluation of hepatic fibrosis
      in patients with chronic hepatitis B: a prospective multicenter study.
AB  - BACKGROUND: The prognosis and management of hepatic fibrosis are closely related
      to the stage of the disease. The limitations of liver biopsy, which is the gold
      standard for treatment, include its invasiveness and sampling error. Ultrasound
      elasticity might be the most promising imaging technology for the noninvasive and
      accurate assessment of hepatic fibrosis. Real-time tissue elastography (RTE)
      measures the relative stiffness of the tissue in the region of interest caused by
      the heartbeat. Many studies have verified that RTE is useful for the diagnosis of
      hepatic fibrosis in patients with chronic hepatitis C (CHC). PURPOSE: To
      determine the formula of the liver fibrosis index for chronic hepatitis B (BLFI)
      and to validate the diagnostic accuracy of the BLFI for hepatic fibrosis compared
      with the liver fibrosis index (LFI). MATERIALS AND METHODS: RTE was performed in
      747 prospectively enrolled patients with chronic hepatitis B (CHB) or cirrhosis
      from 8 centers in China; 375 patients were analyzed as the training set, and 372
      patients were evaluated as the validation set. The fibrosis stage was diagnosed
      from pathological specimens obtained by ultrasound-guided liver biopsy. Nine
      image features were measured from strain images, and the new formula for the BLFI
      was obtained by combining the nine imaging features of the RTE images using
      multiple regression analysis of the training set. The BLFI and LFI were compared
      with the pathological fibrosis stage at diagnosis, and the diagnostic
      performances of the indexes were compared. RESULTS: The Spearman correlation
      coefficient between the BLFI and hepatic fibrosis stages was significantly
      positive (r = 0.711, p < 0.001), and significant differences were present between
      all disease stages. The areas under the receiver-operating characteristic (AUROC)
      curves of the BLFI and LFI for predicting significant fibrosis (S0-S1 vs. S2-S4)
      were 0.858 and 0.858, respectively. For cirrhosis (S0-S3 vs. S4), the AUROC
      curves of the BLFI and LFI were 0.868 and 0.862, respectively. CONCLUSION: The
      results of this large, multicenter study confirmed that RTE is valuable for the
      diagnosis of hepatic fibrosis in patients with CHB. However, the diagnostic
      efficiencies of the new BLFI and the original LFI, which were based on CHC, for
      the assessment of CHB hepatic fibrosis were similar; thus, the LFI has the
      potential to be used to directly evaluate the extent of hepatic fibrosis in
      patients with CHB.

PMID- 25376300
TI  - Bright white-light emission from a novel donor-acceptor organic molecule in the
      solid state via intermolecular charge transfer.
AB  - Bright white-light emission was obtained from a novel pyridinium molecule by
      aggregation. Photophysical, single-crystal structural, and computational studies
      demonstrated that an additional low-energy emission was generated by the
      excitation of a new intermolecular charge-transfer (CT) band at the ground state
      that cooperates with the non-quenched high-energy monomer emission to produce
      white light. 

PMID- 25376301
TI  - Ultrafast propagation of beta-amyloid fibrils in oligomeric cloud.
AB  - Interaction between monomer peptides and seeds is essential for clarifying the
      fibrillation mechanism of amyloid beta (Abeta) peptides. We monitored the
      deposition reaction of Abeta(1-40) peptides on immobilized seeds grown from
      Abeta(1-42), which caused formation of oligomers in the early stage. The
      deposition reaction and fibrillation procedure were monitored throughout by novel
      total-internal-reflection-fluorescence microscopy with a quartz-crystal
      microbalance (TIRFM-QCM) system. This system allows simultaneous evaluation of
      the amount of deposited peptides on the surface seeds by QCM and fibril
      nucleation and elongation by TIRFM. Most fibrils reached other nuclei, forming
      the fibril network across the nucleus hubs in a short time. We found a fibril
      elongation rate two-orders-of-magnitude higher in an oligomeric cloud than
      reported values, indicating ultrafast transition of oligomers into fibrils.

PMID- 25376304
TI  - Influence of steviol glycosides on the stability of vitamin C and anthocyanins.
AB  - A high level of sweetness and health-promoting properties make steviol glycosides
      an interesting alternative to sugars or artificial sweeteners. The radical oxygen
      species scavenging activity of these compounds may influence the stability of
      labile particles present in food. Model buffer solutions containing steviol
      glycosides, a selected food antioxidant (vitamin C or anthocyanins), and
      preservative were analyzed during storage. The addition of steviol glycosides at
      concentrations of 50, 125, and 200 mg/L increased the stability of both ascorbic
      and dehydroascorbic acid (degradation rates decreased up to 3.4- and 4.5-fold,
      respectively); the effect was intensified by higher sweetener concentrations and
      higher acidity of the solutions. Glycosides used alone did not affect the
      stability of anthocyanins; however, they enhanced the protective effect of
      sugars; half-life times increased by ca. 33% in the presence of sucrose (100 g/L)
      and by ca. 52% when both sucrose (100 g/L) and glycosides (total 200 mg/L) were
      used. Steviol glycosides concentrations remained stable during experiments. 

PMID- 25376302
TI  - Plasmalemmal Vesicle Associated Protein (PLVAP) as a therapeutic target for
      treatment of hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy with poor survival
      outcome. New treatment options for the disease are needed. In this study, we
      identified and evaluated tumor vascular PLVAP as a therapeutic target for
      treatment of HCC. METHODS: Genes showing extreme differential expression between
      paired human HCC and adjacent non-tumorous liver tissue were investigated. PLVAP
      was identified as one of such genes with potential to serve as a therapeutic
      target for treatment of HCC. A recombinant monoclonal anti-PLVAP Fab fragment co
      expressing extracellular domain of human tissue factor (TF) was developed. The
      potential therapeutic effect and toxicity to treat HCC were studied using a Hep3B
      HCC xenograft model in SCID mice. RESULTS: PLVAP was identified as a gene
      specifically expressed in vascular endothelial cells of HCC but not in non
      tumorous liver tissues. This finding was confirmed by RT-PCR analysis of micro
      dissected cells and immunohistochemical staining of tissue sections. Infusion of
      recombinant monoclonal anti-PLVAP Fab-TF into the main tumor feeding artery
      induced tumor vascular thrombosis and extensive tumor necrosis at doses between
      2.5 MUg and 12 MUg. Tumor growth was suppressed for 40 days after a single
      treatment. Systemic administration did not induce tumor necrosis. Little systemic
      toxicity was noted for this therapeutic agent. CONCLUSIONS: The results of this
      study suggest that anti-PLVAP Fab-TF may be used to treat HCC cases for which
      transcatheter arterial chemoembolization (TACE) is currently used and potentially
      avoid the drawback of high viscosity of chemoembolic emulsion for TACE to improve
      therapeutic outcome. Anti-PLVAP Fab-TF may become a viable therapeutic agent in
      patients with advanced disease and compromised liver function.

PMID- 25376303
TI  - Climate warming increases biological control agent impact on a non-target
      species.
AB  - Climate change may shift interactions of invasive plants, herbivorous insects and
      native plants, potentially affecting biological control efficacy and non-target
      effects on native species. Here, we show how climate warming affects impacts of a
      multivoltine introduced biocontrol beetle on the non-target native plant
      Alternanthera sessilis in China. In field surveys across a latitudinal gradient
      covering their full distributions, we found beetle damage on A. sessilis
      increased with rising temperature and plant life history changed from annual to
      perennial. Experiments showed that elevated temperature changed plant life
      history and increased insect overwintering, damage and impacts on seedling
      recruitment. These results suggest that warming can shift phenologies, increase
      non-target effect magnitude and increase non-target effect occurrence by beetle
      range expansion to additional areas where A. sessilis occurs. This study
      highlights the importance of understanding how climate change affects species
      interactions for future biological control of invasive species and conservation
      of native species.

PMID- 25376305
TI  - Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx
      mantelli.
AB  - The ability to function in a nocturnal and ground-dwelling niche requires a
      unique set of sensory specializations. The New Zealand kiwi has shifted away from
      vision, instead relying on auditory and tactile stimuli to function in its
      environment and locate prey. Behavioral evidence suggests that kiwi also rely on
      their sense of smell, using olfactory cues in foraging and possibly also in
      communication and social interactions. Anatomical studies appear to support these
      observations: the olfactory bulbs and tubercles have been suggested to be large
      in the kiwi relative to other birds, although the extent of this enlargement is
      poorly understood. In this study, we examine the size of the olfactory bulbs in
      kiwi and compare them with 55 other bird species, including emus, ostriches,
      rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine
      the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine
      if any neural specializations beyond size are present that would increase
      olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs
      that are proportionately larger than those of any other bird in this study. Emus,
      close relatives of the kiwi, also had a relative enlargement of the olfactory
      bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The
      olfactory bulbs in kiwi are almost in direct contact with the olfactory
      epithelium, which is indeed well developed and complex, with olfactory receptor
      cells occupying a large percentage of the epithelium. The anatomy of the kiwi
      olfactory system supports an enhancement for olfactory sensitivities, which is
      undoubtedly associated with their unique nocturnal niche.

PMID- 25376306
TI  - The effect of environmental exposure to pyrethroids and DNA damage in human
      sperm.
AB  - The present study was designed to investigate whether environmental exposure to
      pyrethroids was associated with sperm DNA damage. Between January 2008 and April
      2011 286 men under 45 years of age with a normal sperm concentration of 15-300
      10(6)/ml [WHO 2010] were recruited from an infertility clinic in Lodz, Poland.
      Participants were interviewed and provided urine, saliva, and semen samples. The
      pyrethroids metabolites: 3-phenoxybenzoic acid (3PBA), cis-3-(2,2-dichlorovinyl)
      2,2-dimethylcyclopropane carboxylic acid (CDCCA), trans-3-(2,2-dichlorovinyl)-2,2
      dimethylcyclopropane carboxylic acid (TDCCA), and cis-2,2-dibromovinyl-2,2
      dimethylcyclopropane-carboxylic acid (DBCA) were analyzed in the urine using a
      validated gas chromatography ion-tap mass spectrometry method. Sperm DNA damage
      was assessed using a flow cytometry based on sperm chromatin structure assay
      (SCSA). A positive association was observed between CDCCA >50th percentile and
      the percentage of medium DNA fragmentation index (M DFI) and percentage of
      immature sperms (HDS) (p = 0.04, p = 0.04 respectively). The level of 3PBA >50th
      percentile in urine was positively related to the percentage of high DNA
      fragmentation index (H DFI) (p = 0.03). The TDCCA, DBCA levels, and the sum of
      pyrethroid metabolites were not associated with any sperm DNA damage measures.
      Our results suggest that environmental pyrethroid exposure may affect sperm DNA
      damage measures index indicated the reproductive effects of pyrethroid exposure
      on adult men. In view of the importance of human reproductive health and the
      widespread usage of pyrethroids, it is important to further investigate these
      correlations.

PMID- 25376307
TI  - Paraplegia in a patient with Von Hippel Lindau syndrome: surgical and
      reconstructive treatment of Marjolin's ulcer. A case report.
AB  - STUDY DESIGN: Marjolin's ulcer is a squamous cell carcinoma that develops in
      posttraumatic scars and chronic wounds. Suspicion of such lesions should be
      raised in chronic wounds demonstrating characteristic changes. We have reported
      the peculiar phenomenon of malignant transformation of chronic pressure sores
      that occurred in a paraplegic patient. OBJECTIVES: The aim of this study was to
      cover the extensive defects by a last resort reconstructive option. SETTING:
      Department of Plastic and Reconstructive Surgery, Universita Politecnica delle
      Marche, Ancona, Italy. METHODS AND RESULTS: A 40-year-old paraplegic man, with
      multiple hemangioblastomas of the brain and spinal cord due to Von Hippel Lindau
      syndrome developed pressure ulcers with unstable healing over the sacral,
      trochanteric, bilateral, and ischiatic areas after 15 years from neurosurgery.
      The biopsy result showed an invasive squamous carcinoma. Carcinomas in pressure
      sores are highly aggressive, and they need to be treated more radically. In our
      case we opted for a demolitive surgical treatment including musculocutaneous
      rotational flap harvested from total left thigh to cover the extensive defects.
      The limb was previously disarticulated. CONCLUSION: In Marjolin's ulcer, multiple
      biopsies are the first-line modality for the early diagnosis as they are a safe
      method with high rate of accuracy. First-line treatment is surgery consisting of
      radical excision with lymph node dissection, if they are involved. Adjuvant
      radiation therapy may be used in selected patients. Management of massive pelvic
      defects can be a challenging problem. The pedicled lower limb flap offers a
      technique that can be considered as a last resort procedure for extensive defects
      where other options are insufficient or not available anymore. In our case the
      patient is disease-free after 2 years of follow-up.

PMID- 25376308
TI  - Glucose uptake of the spinal cord in patients with multiple sclerosis detected by
      18F-fluorodeoxyglucose PET/CT after walking.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To determine [(18)F]-fluorodeoxyglucose
      ([(18)F]-FDG) uptake in the spinal cord of patients with multiple sclerosis (MS)
      was compared with healthy controls after treadmill walking. SETTING: Colorado
      Translational Research Imaging Center, University of Colorado School of Medicine,
      Aurora, CO, USA. METHODS: Eight mildly disabled patients with MS and eight
      healthy subjects performed 15 min of treadmill walking at a self-selected pace.
      Two minutes after walking began, each participant was injected with ~8 mCi of
      [(18)F]-FDG into a catheter inserted into an antecubital vein. Immediately after
      walking positron emission tomography/computed tomography (PET/CT) imaging was
      performed on each participant. Images were analyzed to determine [(18)F]-FDG
      uptake within the spinal cord. RESULTS: Total spinal cord [(18)F]-FDG uptake was
      lower in patients with MS (1.48+/-0.36 and 1.55+/-0.33, P=0.04), specifically
      within the thoracic (1.32+/-0.27 and 1.41+/-0.24, P<0.01) and the lumbar (1.58+/
      0.40 and 1.89+/-0.43, P=0.04) spinal cord regions. CONCLUSION: This is the first
      report of [(18)F]-FDG uptake in the spinal cord of patients with MS. The
      decreased [(18)F]-FDG uptake within the thoracic and lumbar spinal cord regions
      could be associated with autonomic nervous system and walking/motor dysfunctions
      that are often seen in patients with MS. PET/CT imaging with [(18)F]-FDG is
      highly useful for the demonstration of impaired glucose metabolism in the spinal
      cord of patients with MS.

PMID- 25376309
TI  - Rehabilitation for paraplegia caused by neuromyelitis optica: a case report.
AB  - STUDY DESIGN: Single case report. OBJECTIVE: We present a case of paraplegia due
      to neuromyelitis optica (NMO) with poor rehabilitation outcome. SETTING:
      University hospital, Japan. CASE REPORT: A 27-year-old woman with NMO presented
      with T5 paraplegia of ASIA impairment scale grade A. Spinal cord magnetic
      resonance imaging revealed a lesion spanning C3 to L1 level. After acute phase
      treatment, flaccid paraplegia below T5 and a T2-weighted hyperintense lesion from
      T6 to T10 level remained. Rehabilitation aimed at independence of activities of
      daily living with wheelchair assistance, including transfer activity, was
      provided for 19 months. However, flaccid paralysis of the trunk and limbs
      persisted, and safe independent transfer was not achieved. CONCLUSION: Spinal
      lesions spanning many vertebral segments, a characteristic of NMO, can cause
      extensive flaccid paralysis of the trunk and limbs. Rehabilitation may achieve
      poorer functional recovery than that for spinal cord injury.

PMID- 25376310
TI  - Hiccup-like segmental myoclonus in thoracic compressive myelopathy: a case
      report.
AB  - STUDY DESIGN: A case report. OBJECTIVES: This study discusses a case of spinal
      segmental myoclonus caused by thoracic myelopathy, mimicking hiccup spasms.
      Spinal myoclonus caused by thoracic myelopathy is extremely rare. It can be
      misdiagnosed as chronic intractable hiccups due to similar clinical
      manifestations. SETTING: Korea University Anam Hospital, Seoul, Republic of
      Korea. METHODS: A 42-year-old man presented with a history of involuntary jerky
      movement of the upper abdominal wall muscles that had been continuing for over 3
      years. A neurological examination, brain computed tomography and
      electroencephalogram did not reveal a cause of the symptoms. Electromyography was
      performed on the abdominal muscles and the findings revealed were compatible with
      spinal myoclonus. The spinal myoclonus had started in the abdominal muscles, with
      a spinal magnetic resonance imaging revealing a disc protrusion compressing the
      anterior spinal cord. RESULTS: The cause of the spinal myoclonus was determined
      to be spinal myelopathy due to mild T7 disc protrusion. The patient refused
      surgical or invasive interventions and was conservatively treated with
      clonazepam. The symptoms were reported to be less frequent following the
      treatment. CONCLUSION: Compressive myelopathy developed from disc protrusion may
      cause spinal myoclonus mimicking as hiccup spasms.

PMID- 25376311
TI  - Resection of spinous processes can cause spinal cord injury in patient with
      ossification of the posterior longitudinal ligament in the thoracic spine.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report intraoperative spinal cord injury
      by resection of spinous processes in a 73-year-old man with ossification of the
      posterior longitudinal ligament (OPLL) in the thoracic spine. METHODS: A 73-year
      old man presented with cervicothoracic OPLL with bilateral numbness and
      clumsiness of his hand, weakness of his lower extremities and severe gait
      disturbance. His Japanese Orthopaedic Association (JOA) score was 7.5 out of 17.
      Cervical laminoplasty (C2-6), cervicothoracic laminectomy (C7-T10) and posterior
      fusion (C7-T10) were performed in the prone position with electrophysiologic
      monitoring of the spinal cord-evoked potentials (SCEPs). RESULTS: The spinal
      processes with supra- and interspinous ligaments between C7 and T10 were
      resected. After resection, the amplitude of SCEP waveforms decreased rapidly to
      <10% of control levels. Laminectomy was performed, and, after 80 min of SCEP
      deterioration, an instrumented fusion with correction for kyphosis was completed.
      The SCEP amplitude recovered gradually. Immediately after surgery, the patient
      suffered severe motor loss in both lower limbs. His neurological recovery
      progressed gradually from 2 days after surgery, and he was able to walk at 3
      months after surgery. At 6 years after surgery, the JOA score was 11. CONCLUSION:
      Our results suggest that intraoperative spinal cord injury can occur before
      posterior decompression by resection of spinal processes with supra- and
      interspinous ligaments. The timing of the instrumented stabilization using a
      temporary rod is important and should be considered immediately after posterior
      exposure of the spine.

PMID- 25376312
TI  - Emergency surgery in a patient with large spontaneous spinal epidural hematoma
      determining excellent neurological recovery: review of the literature.
AB  - STUDY DESIGN: Case report. OBJECTIVES: We report a case of a 75-year-old woman
      suffering from voluminous idiopathic spontaneous spinal epidural hematoma (SSEH)
      that was rapidly diagnosed and successfully treated. METHODS: Clinical
      presentation was characterized by sudden and intense back pain that rapidly
      evolved into plegia of the right leg and severe paresis of the left leg.
      Hypoesthesia below T6 and urinary retention were also present. Magnetic resonance
      imaging showed a significant posterior spinal compression from T6 through L3
      caused by an epidural hematoma that involved 10 metameric levels, extending for
      ~20 cm, with a maximum thickness of 1.6 cm from T12 to L1. RESULTS: Within 12 h,
      emergency decompressive laminectomy from T10 to L1 was performed, and evacuation
      of the hematoma was achieved. The postoperative course and neurological recovery
      of the patient were optimal. After discharge, the patient continued the
      rehabilitative treatment started during hospitalization, achieving an excellent
      functional outcome in 1 month. CONCLUSIONS: Spinal epidural hematoma (SEH) is a
      rare clinical finding that can occur following trauma or spontaneously (SSEH). We
      describe, to the best of our knowledge, the second most extensive idiopathic SSEH
      and the longest with involvement of the dorso-lumbar spine that had a excellent
      functional outcome due to emergency decompressive laminectomy, which is
      emphasized in the treatment of these rare pathologies.

PMID- 25376313
TI  - Can FES-rowing mediate bone mineral density in SCI: a pilot study.
AB  - STUDY DESIGN: A single case study. OBJECTIVES: To compare proximal tibia
      trabecular bone mineral density (BMD) of a participant with complete spinal cord
      injury (SCI), long-termed functional electrical stimulation-rowing (FES-R)
      trained, with previously reported SCI and non-SCI group norms. To estimate lower
      limb joint contact forces (JCFs) in the FES-R trained participant. SETTING: UK
      University and orthopaedic hospital research centre. METHODS: Bilateral proximal
      tibial trabecular BMD of the FES-R trained participant was measured using
      peripheral quantitative computerised tomography, and the data were compared with
      SCI and non-SCI groups. An instrumented four-channel FES-R system was used to
      measure the lower limb JCFs in the FES-R trained participant. RESULTS:
      Structurally, proximal tibial trabecular BMD was higher in the FES-R trained
      participant compared with the SCI group, but was less than the non-SCI group.
      Furthermore, left (184.7 mg cm(-3)) and right (160.7 mg cm(-3)) BMD were well
      above the threshold associated with non-traumatic fracture. The knee JCFs were
      above the threshold known to mediate BMD in SCI, but below threshold at the hip
      and ankle. CONCLUSION: As pathological fractures predominate in the distal femur
      and proximal tibia in chronic SCI patients, the fact that the FES-R trained
      participant's knee JCFs were above those known to partially prevent bone loss,
      suggests that FES-R training may provide therapeutic benefit. Although the
      elevated bilateral proximal tibial BMD of the FES-R participant provides
      circumstantial evidence of osteogenesis, this single case precludes any statement
      on the clinical significance. Further investigations are required involving
      larger numbers and additional channels of FES to increase loading at the hip and
      ankle.

PMID- 25376314
TI  - Pulmonary embolism after manual muscle testing in an incomplete paraplegic
      patient: a case report.
AB  - OBJECTIVE: To report and discuss the case of an incomplete paraplegic patient who
      died of pulmonary embolism (PE) aggravated by manual muscle testing. SETTING:
      Acute spinal ward, Maharaj Hospital, Chiang Mai, Thailand. CASE REPORT: A 79-year
      old man suffering from chest trauma, fractured ribs and a fracture of T11 with
      incomplete paraplegia, American Spinal Injury Association impairment scale D.
      Intercostal tubes were inserted at both sides due to haemothorax. Ten days after
      onset, T9 to L2 posterior instrumentation was successfully completed. A week
      after the operation, he was allowed to stand on a tilt-table and a rehabilitation
      specialist was consulted to assess and plan to encourage ambulation. After manual
      muscle testing of the right hip flexors and knee extensors, the patient suffered
      from a short period of unconsciousness and breathlessness. Electrocardiography
      showed right bundle branch block and a drop in oxygen saturation from 98 to 70%.
      After oxygenation with mask and bag, oxygen saturation increased to 90%. PE or
      acute myocardial infarction was suspected. After insertion of an endotracheal
      tube, the patient went into cardiac arrest. Cardiopulmonary resuscitation failed.
      The autopsy revealed large and small thromboemboli in both lungs, particularly in
      the pulmonary artery. CONCLUSION: Strong hip and knee muscle contractions during
      manual muscle testing were suspected of triggering massive pulmonary emboli from
      the proximal vein of the right leg of a paraplegic patient who had functional
      motor movements and did not receive any thromboembolic prophylaxis which caused
      unexpected fatal pulmonary emboli. Screening of venous thromboembolism risks and
      its symptoms/signs before mobilisation is mandatory.

PMID- 25376315
TI  - Spinal cord infarction in carriers of methylenetetrahydrofolate reductase
      polymorphism-like unique risk factor: report of two cases.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To present two cases of spinal cord
      infarction (SCI) in carriers of the C677T methylenetetrahydrofolate reductase
      (MTHFR) polymorphism. SETTING: Physical Medicine and Rehabilitation Department,
      Section for Rehabilitation and Traumatology, Hospital Virgen de las Nieves,
      Granada, Spain. METHODS: Two cases are presented, one with SCI at the C7 level
      American Spinal Injury Association (ASIA) A and one at the C5 level (ASIA A). One
      patient presented an acute onset of tetraplegia and the other a centromedular
      syndrome. In both cases the patients were carriers of the MTHFR polymorphism,
      which is a unique risk factor. RESULTS: Increased blood levels of homocysteine
      related to mutation of the MTHFR gene increase the risk of a thrombotic episode,
      triggering the development of SCI. These two cases increase the limited number
      reported in the recent literature regarding MTHFR polymorphism carriers suffering
      from thrombotic SCI. CONCLUSION: MTHFR mutation can be considered a risk factor
      for thrombotic SCI, but it is not the sole risk factor. We propose that a
      consensus regarding the inclusion of anticoagulation treatment after confirmation
      of the diagnosis in these patients is needed.

PMID- 25376317
TI  - I never stop...accepting challenges.

PMID- 25376318
TI  - Never stop accepting challenges.

PMID- 25376316
TI  - Characterization of microRNA expression profiles in Leishmania-infected human
      phagocytes.
AB  - Leishmania are intracellular protozoa that influence host immune responses
      eliciting parasite species-specific pathologies. MicroRNAs (miRNAs) are short
      single-stranded ribonucleic acids that complement gene transcripts to block
      protein translation and have been shown to regulate immune system molecular
      mechanisms. Human monocyte-derived dendritic cells (DC) and macrophages (MP) were
      infected in vitro with Leishmania major or Leishmania donovani parasites. Small
      RNAs were isolated from total RNA and sequenced to identify mature miRNAs
      associated with leishmanial infections. Normalized sequence read count profiles
      revealed a global downregulation in miRNA expression among host cells following
      infection. Most identified miRNAs were expressed at higher levels in L. donovani
      infected cells relative to L. major-infected cells. Pathway enrichments using in
      silico-predicted gene targets of differentially expressed miRNAs showed evidence
      of potentially universal MAP kinase signalling pathway effects. Whereas JAK-STAT
      and TGF-beta signalling pathways were more highly enriched using targets of
      miRNAs upregulated in L. donovani-infected cells, these data provide evidence in
      support of a selective influence on host cell miRNA expression and regulation in
      response to differential Leishmania infections.

PMID- 25376319
TI  - Parenteral nutrition with standard solutions: not the best solution for everyone?
      A retrospective audit of 300 patients.
AB  - An observational retrospective study audited the incidence of adverse events in
      300 consecutive inpatients receiving a single, premade total nutrient admixture.
      No patient experienced critically high triglycerides; 16% of patients had a
      metabolic adverse event, including raised bilirubin, urea, creatinine, or liver
      enzymes. Line sepsis occurred on 30 occasions representing 0.67 infections per
      1000 catheter days. Mortality was significantly higher in dialysis, nonsurgical,
      and intensive care unit patients. The use of a standard formulation for all
      parenterally nourished patients does not lead to an unacceptable incidence or
      severity of metabolic complications; however, it did not meet the protein
      requirements of surgical or critically ill patients.

PMID- 25376320
TI  - Survey of heat use during peripheral IV insertion by health care workers.
AB  - Health care workers at an academic medical center in the Midwest were surveyed to
      identify common practices regarding heat use during peripheral intravenous (PIV)
      catheter insertion. Of the 907 who responded, the majority used heat to
      facilitate PIV insertion at least sometimes, when veins were not easily seen or
      not palpable, applying a commercial dry hot pack for 2 to 5 minutes before
      selecting an insertion site. Heat use correlated with practice role and
      population, frequency of PIV insertion, and perceived PIV skill. Findings will
      guide development of a research protocol to compare the effects of dry heat,
      moist heat, and no heat on PIV insertion success. 

PMID- 25376321
TI  - Management of the patient with pulmonary arterial hypertension receiving
      intravenous prostacyclin: an expert nurse practical guide.
AB  - Pulmonary arterial hypertension (PAH) is a severely disabling disorder
      characterized by elevated pulmonary artery pressure ultimately leading to right
      heart failure and death. Treatment options have significantly increased over the
      past decade. Intravenous prostacyclins remain the treatment of choice for
      advanced PAH, leading to long-term clinical benefits and improved survival. Their
      administration requires a high level of nursing competency and presents
      considerable challenges for patients and caregivers. This article reviews the
      characteristics of currently available intravenous prostacyclins and provides a
      practical guide for nurses who may have had limited exposure to intravenous
      prostacyclins and their unique dosing, side effects, and titration
      characteristics. 

PMID- 25376322
TI  - Peripheral amiodarone-related phlebitis: an institutional nursing guideline to
      reduce patient harm.
AB  - Intravenous amiodarone is one of the most widely used antiarrythmics for the
      treatment of atrial fibrillation with rapid ventricular response. Peripheral
      amiodarone infusion, however, often causes pain during infusion and subsequent
      phlebitis.Data collection on a cardiac telemetry unit revealed a high rate of
      phlebitis. A multidisciplinary team developed and implemented amiodarone
      peripheral infusion guidelines. The pre-guideline phlebitis rate was 85% and post
      guideline rate was 38%, representing a 47% change or improvement. An additional
      finding was that the severity of phlebitis was reduced, as well. The results of
      this study suggest that the implementation of a peripheral amiodarone infusion
      guideline reduced the incidence and severity of amiodarone-related phlebitis in
      the cardiac population. 

PMID- 25376323
TI  - A successful approach to reducing bloodstream infections based on a disinfection
      device for intravenous needleless connector hubs.
AB  - When central line-associated bloodstream infections (CLABSIs) spiked in an
      oncology unit of an acute care hospital in Philadelphia from October 2009 to
      March 2010, noncompliance with intravenous needleless connector disinfection was
      suspected as a factor. The hospital implemented a disinfection cap, a device
      designed to address compliance/variance issues with connector disinfection
      protocols. However, the incidence of CLABSIs increased again in 1 unit,
      apparently as the result of poor compliance with cap use. The hospital addressed
      the problem with multiple measures, after which the incidence of CLABSIs again
      continued to decline. Overall, 50% fewer CLABSIs occurred in the first 21 months
      after cap implementation. Potential net financial savings from cap use were
      calculated to be $464,440 a year.

PMID- 25376324
TI  - Cutting peripherally inserted central catheters may lead to increased rates of
      catheter-related deep vein thrombosis.
AB  - The purpose of this study was to determine whether an association exists between
      cutting or trimming peripherally inserted central catheters (PICCs) and the
      development of deep vein thromboses (DVTs). An observational, retrospective study
      was conducted on 634 patients who had a PICC inserted between 2011 and 2012.
      Patients who had a reverse-taper PICC inserted were assigned into 1 of 2 groups.
      The first group included patients with a reverse-taper PICC that was cut/trimmed
      (PC) before insertion (n = 224). The second group was made up of patients whose
      PICC was not cut/trimmed (PNC) before insertion (n = 410). All PICC-associated
      DVTs were confirmed by a positive venous Doppler result and recorded. A
      statistically significant difference (P < .001) was found between patients in the
      PC group who developed a DVT (9.82%) and patients in the PNC group in which PICCs
      were not trimmed (1.95%). There is evidence to suggest that altering the reverse
      taper PICC by cutting or trimming the tip before insertion may be associated with
      increased DVTs. Further study is required to determine whether PICCs should be
      reduced in length or whether there is an appropriate method of trimming the
      catheter to ensure its stability after insertion. 

PMID- 25376325
TI  - Soy allergy complicating disease management in a child with coeliac disease.

PMID- 25376326
TI  - Nursing casualization and communication: a critical ethnography.
AB  - AIM: The aim was to explore the relationship between nursing casualization and
      the culture of communication for nurses in a healthcare facility. BACKGROUND:
      Casualization, or non-standard work, is the use of temporary, contract, part-time
      and casual labour. An increase in casual labour has been part of a global shift
      in work organization aimed at creating a more flexible and cheaper workforce. It
      has been argued that flexibility of labour has enabled nurses to manage both non
      work related needs and an increasingly complex work environment. Yet no research
      has explored casualization and how it impacts on the communication culture for
      nurses in a healthcare facility. DESIGN: Critical ethnography. METHODS: Methods
      included observation, field notes, formal interviews and focus groups. Data
      collection was undertaken over the 2 years 2008-2009. RESULTS: The concepts of
      knowing and belonging were perceived as important to nursing teamwork and yet the
      traditional time/task work model, designed for a full-time workforce,
      marginalized non-standard workers. The combination of medical dominance and
      traditional stereotyping of the nurse and work as full-time shaped the behaviours
      of nurses and situated casual workers on the periphery. The overall finding was
      that entrenched systemic structures and processes shaped the physical and
      cultural dimensions of a contemporary work environment and contributed to an
      ineffective communication culture. CONCLUSION: Flexible work is an important
      feature of contemporary nursing. Traditional work models and nurse attitudes and
      practices have not progressed and are discordant with a contemporary approach to
      nursing labour management.

PMID- 25376327
TI  - Identification and characterization of intestinal lactobacilli strains capable of
      degrading immunotoxic peptides present in gluten.
AB  - AIM: Identify and characterize bacteria from the proximal gastrointestinal tract
      of pigs capable of degrading immunogenic gluten peptides. METHODS AND RESULTS:
      Bacteria were cultured from the small intestine of pigs fed a 20% gluten diet and
      from an enrichment media with the 18-mer peptide LQLQPFPQPQLPYPQPQL. Isolates
      were screened for the production of specialized proteolytic enzymes and the
      ability to degrade and remove metastable peptides from alpha-gliadin (16-mer and
      33-mer) and omega-gliadin (17-mer), with established roles in the aetiology of
      coeliac disease. Degradation was determined by ELISA and mass spectrometry (UHPLC
      MS/MS in MRM mode), and hydrolysis fragments were characterized by LC-MS/MS. Four
      strains from the species Lactobacillus ruminis, Lactobacillus johnsonii,
      Lactobacillus amylovorus and Lactobacillus salivarius showed the highest peptide
      degrading activities. Strains displayed different degradation rates and cleavage
      patterns that resulted in reduction but not complete removal of immunotoxic
      epitopes. CONCLUSIONS: We employed a unique enrichment process to select for
      bacteria adapted to the conditions of the proximal gastrointestinal tract with
      the ability to partially detoxify well-characterized peptides involved in coeliac
      disease. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a basis for
      the selection of Lactobacillus strains for probiotic applications aimed to reduce
      epitope-containing gluten peptides before reaching the epithelium of the small
      intestine of patients with coeliac disease.

PMID- 25376328
TI  - The effect of coughing at extubation on oxygenation in the post-anaesthesia care
      unit.
AB  - We prospectively studied 84 patients to investigate whether there is a
      relationship between coughing during emergence and tracheal extubation, and
      impaired oxygenation in the post-anaesthesia care unit. Our primary outcome
      measure was a change in the alveolar-arterial oxygen partial pressure gradient
      ((A-a)DO2 ) between time A (during general anaesthesia) and time B (1 h after
      extubation). Patients demonstrated a worsening of oxygenation with mean (SD) (A
      a)DO2 increasing from 7.5 (5.2) kPa at time A to 13.9 (4.2) kPa at time B (p <
      0.01). An overall linear regression model was not predictive for the observed
      change (adjusted R(2) = 0.01, p = 0.31) and nor were any of the individual
      predictors studied, including subjective cough score (p = 0.33), number of coughs
      (p = 0.95) and duration of coughing (p = 0.39). Despite the abnormal cough that
      occurs while tracheally intubated, we have been unable to demonstrate that
      coughing at extubation is associated with impaired oxygenation in the immediate
      postoperative period.

PMID- 25376329
TI  - A novel ERCC6 splicing variant associated with a mild Cockayne syndrome
      phenotype.
AB  - BACKGROUND: Cockayne syndrome is an autosomal recessive, heterogeneous syndrome
      with classical features, including short stature, microcephaly, developmental
      delay, neuropathy, and photosensitivity. New genomic approaches offer improved
      molecular diagnostic potential. METHODS: Whole-exome sequencing was employed to
      study a consanguineous extended family with severe short stature and variable
      presentations of peripheral neuropathy, lipoatrophy, photosensitivity, webbed
      neck, and hirsutism. RESULTS: We identified a novel homozygous ERCC6 variant at
      the donor splice site of intron 9 (c.1992 + 3A>G), which was predicted to only
      slightly perturb splicing efficiencies. Assessment of primary fibroblast-derived
      mRNAs, however, revealed a dominant splicing species that utilized an unsuspected
      putative donor splice site within exon 9, resulting in predicted early protein
      termination (p.Arg637Serfs*34). CONCLUSIONS: We describe a new splicing ERCC6
      defect causal of Cockayne syndrome. The application of exome sequence analysis
      was integral to diagnosis, given the complexity of phenotypic presentation in the
      affected family members. The novel splicing defect, furthermore, illustrates how
      a seemingly minor change in the relative strength of a splice site can have
      significant biological consequences.

PMID- 25376330
TI  - Statistical estimation of physiological brain age as a descriptor of senescence
      rate during adulthood.
AB  - Mapping aging-related brain structure and connectivity changes can be helpful for
      assessing physiological brain age (PBA), which is distinct from chronological age
      (CA) because genetic and environmental factors affect individuals differently.
      This study proposes an approach whereby structural and connectomic information
      can be combined to estimate PBA as an early biomarker of brain aging. In a cohort
      of 136 healthy adults, magnetic resonance and diffusion tensor imaging are
      respectively used to measure cortical thickness over the entire cortical mantle
      as well as connectivity properties (mean connectivity density and mean fractional
      anisotropy) for white matter connections. Using multivariate regression, these
      measurements are then employed to (1) illustrate how CA can be predicated--and
      thereby also how PBA can be estimated--and to conclude that (2) healthy aging is
      associated with significant connectome changes during adulthood. Our study
      illustrates a connectomically-informed statistical approach to PBA estimation,
      with potential applicability to the clinical identification of patients who
      exhibit accelerated brain aging, and who are consequently at higher risk for
      developing mild cognitive impairment or dementia.

PMID- 25376331
TI  - Inflammation as a mediator of the relationship between cortical thickness and
      metabolic syndrome.
AB  - Metabolic Syndrome (MetS), the clustering of obesity, high blood pressure, and
      disordered glucose and lipid/lipoprotein metabolism within a single individual,
      is associated with poorer cognitive function. It has been hypothesized that
      cognitive impairment in MetS occurs primarily within the context of inflammation.
      MetS risk factors are also associated with thinning of the cerebral cortex.
      However, the mechanisms by which MetS and inflammation affect the brain are
      poorly understood. The present study used statistical mediation to examine the
      relationship between MetS risk factors, cortical thickness in a priori regions of
      interest (ROIs) and inflammation. ROIs were chosen from the previous literature.
      Forty-three adults between the ages of 40 and 60 years underwent a health screen,
      neuropsychological testing and structural magnetic resonance imaging. Serum
      levels of pro-inflammatory markers (interleukin 1, interleukin 2, interleukin 6
      and C-Reactive Protein) were measured using enzyme-linked immunosorbent assays. A
      higher number of MetS risk factors were associated with thinning in the inferior
      frontal ROI (beta = -0.35, p = 0.019) as well as higher levels of serum
      interleukin 2 (beta = 0.31, p = 0.04). A higher level of serum interleukin 2 was
      also associated with reduced thickness in the inferior frontal gyrus (beta = 
      0.41, p = 0.013). After accounting for the effects of interleukin 2, the number
      of MetS risk factors was no longer associated with cortical thickness in the
      inferior frontal gyrus indicating successful statistical mediation. The results
      indicate a potentially important role for inflammation in linking MetS to
      cortical thinning and cognitive vulnerability. 

PMID- 25376333
TI  - Development of a markerless gene replacement system in Corynebacterium glutamicum
      using upp as a counter-selection marker.
AB  - Corynebacterium glutamicum is well-established for industrial and
      biotechnological applications. However, its genetic manipulation has generally
      lagged behind traditional genetic models. In this study, a counter-selectable
      marker gene upp was firstly confirmed to be more efficient than traditional sacB.
      Furthermore, a markerless gene replacement system was developed by combining upp
      with double-strand break repair caused by the exogenous endonuclease I-SceI.
      Finally, genetic modification using a dsDNA PCR fragment was carried out with the
      expression of recombinase/exonuclease RecE/RecT. Our results show that the
      genetic modification system allows precise and markerless gene replacement
      without altering the chromosome, with a simplified screening procedure to
      generate its modification. 

PMID- 25376332
TI  - Fiber bundle length and cognition: a length-based tractography MRI study.
AB  - Executive function (EF) and cognitive processing speed (CPS) are two cognitive
      performance domains that decline with advanced age. Reduced EF and CPS are known
      to correlate with age-related frontal-lobe volume loss. However, it remains
      unclear whether white matter microstructure in these regions is associated with
      age-related decline in EF and/or CPS. We utilized quantitative tractography
      metrics derived from diffusion-tensor MRI to investigate the relationship between
      the mean fiber bundle lengths (FBLs) projecting to different lobes, and EF/CPS
      performance in 73 healthy aging adults. We measured aspects of EF and CPS with
      the Trail Making Test (TMT), Color-Word Interference Test, Letter-Number
      Sequencing (L-N Seq), and Symbol Coding. Results revealed that parietal and
      occipital FBLs explained a significant portion of variance in EF. Frontal,
      temporal, and occipital FBLs explained a significant portion of variance in CPS.
      Shorter occipital FBLs were associated with poorer performance on the EF tests
      TMT-B and CWIT 3. Shorter frontal, parietal, and occipital FBLs were associated
      with poorer performance on L-N Seq and Symbol Coding. Shorter frontal and
      temporal FBLs were associated with lower performance on CPS tests TMT-A and CWIT
      1. Shorter FBLs were also associated with increased age. Results suggest an age
      related FBL shortening in specific brain regions related to poorer EF and CPS
      performance among older adults. Overall, results support both the frontal aging
      hypothesis and processing speed theory, suggesting that each mechanism is
      contributing to age-related cognitive decline. 

PMID- 25376334
TI  - Improving lesion localisation at colonoscopy: an analysis of influencing factors.
AB  - PURPOSE: Colonoscopy detects colorectal cancer and determines lesion localisation
      that influences surgical planning. However, published work suggests that the
      accuracy of lesion localisation can be low as 60%, with implications for both the
      surgeon and the patient. This work aims to identify potential influencing factors
      at colonoscopy that could lead to improved lesion localisation accuracy. METHODS:
      A multi-centred, prospective, observational study was performed that identified
      patients who were undergoing planned curative resection for a colorectal lesion.
      Localisation of a lesion at colonoscopy was compared to the intra-operative
      lesion localisation to determine accuracy of colonoscopic localisation. Patient
      factors and colonoscopic factors were recorded to determine any influencing
      factors on lesion localisation at colonoscopy. RESULTS: One hundred and eleven
      patients were analysed: mean age 67.4 years (range 27-89); male:female ratio
      1.3:1; symptomatic referrals (n = 78, 70.3%); and previous abdominal surgery in
      27 patients (24.3%). Complete colonoscopy was recorded in 78 patients (70.3%). In
      88 patients (79.3%), colonoscopic lesion localisation matched the intra-operative
      location. Pre-operative CT imaging was unable to identify the tumour in 24 cases
      (21.8%). Potential influencing patient and colonoscopic factors on accurate
      lesion localisation at colonoscopy found complete colonoscopy to be the only
      significant factor (p = 0.008). CONCLUSION: Colonoscopic lesion localisation was
      found to be inaccurate in 79.3% cases, and with pre-operative CT unable to detect
      all lesions, this study confirms that accurate lesion localisation in the modern
      era is increasingly reliant on colonoscopy. Incomplete colonoscopy was the only
      significant factor that influenced inaccurate lesion localisation at colonoscopy.

PMID- 25376335
TI  - What is the necessity of endoscopist for successful endoscopic stenting in
      patients with malignant colorectal obstruction?
AB  - BACKGROUND AND AIM: Recently, self-expandable metal stents (SEMSs) have been
      widely used as an initial therapy for relieving malignant colorectal
      obstructions. However, several factors, including the endoscopist's experience,
      affect the clinical outcome of SEMSs. The aim of this study was to define the
      adequate level of experience necessary to perform endoscopic stenting effectively
      and safely and to identify technical factors for successful stenting. METHODS:
      Between March 2009 and June 2012, 160 patients underwent SEMS placement for
      malignant colorectal obstruction with the intent of palliation or as a bridge to
      surgery by a single endoscopist who experienced colonoscopy and endoscopic
      retrograde cholangiopancreatography. RESULTS: The overall technical and clinical
      success rates were 86.9 and 86.4%, respectively, and 18 complications (11.3%)
      were observed. There were no differences in any of the clinical outcomes between
      the consecutive blocks; however, the procedure time decreased significantly after
      the first 30 procedures (17.4, 16.9, 13.5, and 12.8 min; P = 0.044). American
      Society of Anesthesiologists (ASA) class, history of a previous operation,
      proximal colon obstruction, obstruction caused by an extracolonic malignancy, and
      palliative SEMS placement were associated with technical failure. CONCLUSIONS: An
      endoscopist who experiences a colonoscopy and fluoroscopy performs SEMS placement
      successfully regardless of the level of experience. After the first 30
      procedures, a SEMS insertion could be safely and effectively performed with short
      procedure time in patients with malignant colorectal obstruction.

PMID- 25376336
TI  - Risk factors for wound complications in patients undergoing primary closure of
      the perineal defect after total proctectomy.
AB  - PURPOSE: Perineal wounds after complete proctectomy are at risk for failure, with
      dramatic consequences on patients' health and quality of life. This study is
      aimed at identifying risk factors for wound complications in patients undergoing
      primary closure of the perineal defect after total proctectomy. METHODS: Data
      from 284 patients undergoing total proctectomy from 2002 to 2012 either at the
      University of Chicago Medical Center or the Catholic University of Rome Hospital
      were collected and analyzed. RESULTS: Overall, the perineal wound complication
      rate was 21.8%. Successful conservative management was accomplished in 45.2% of
      cases. Complications occurred significantly more often in patients with a higher
      Charlson score index, with the diagnosis of rectal cancer, who had received
      preoperative radiation and who had a surgical drain placed at the time of initial
      surgery. Neoadjuvant radiation was the only significant risk factor at
      multivariate analysis (OR 4.40). In the rectal cancer subgroup, younger age,
      female gender, and preoperative radiation were predictors of wound complications.
      Based on that, a 3-point score (radiation, age, and gender (RAG)) was developed.
      Patients with a score of 3 had a 50% risk of developing a perineal wound
      complication. CONCLUSIONS: Perineal wound complications are a common and
      burdensome problem after total proctectomy. Preoperative radiation is the single
      most significant and controllable risk factor predicting perineal wound failure.
      In the presence of multiple, non-modifiable risk factors, alternative approaches
      to primary closure should be considered in managing complex perineal defects.

PMID- 25376337
TI  - Hilar cholangiocarcinoma: controversies on the extent of surgical resection
      aiming at cure.
AB  - BACKGROUND: Hilar cholangiocarcinoma is the most common malignant tumor affecting
      the extrahepatic bile duct. Surgical treatment offers the only possibility of
      cure, and it requires removal of all tumoral tissues with adequate resection
      margins. The aims of this review are to summarize the findings and to discuss the
      controversies on the extent of surgical resection aiming at cure for hilar
      cholangiocarcinoma. METHODS: The English medical literatures on hilar
      cholangiocarcinoma were studied to review on the relevance of adequate resection
      margins, routine caudate lobe resection, extent of liver resection, and combined
      vascular resection on perioperative and long-term survival outcomes of patients
      with resectable hilar cholangiocarcinoma. RESULTS: Complete resection of tumor
      represents the most important prognostic factor of long-term survival for hilar
      cholangiocarcinoma. The primary aim of surgery is to achieve R0 resection. When
      R1 resection is shown intraoperatively, further resection is recommended.
      Combined hepatic resection is now generally accepted as a standard procedure even
      for Bismuth type I/II tumors. Routine caudate lobe resection is also advocated
      for cure. The extent of hepatic resection remains controversial. Most surgeons
      recommend major hepatic resection. However, minor hepatic resection has also been
      advocated in most patients. The decision to carry out right- or left-sided
      hepatectomy is made according to the predominant site of the lesion. Portal vein
      resection should be considered when its involvement by tumor is suspected.
      CONCLUSION: The curative treatment of hilar cholangiocarcinoma remains
      challenging. Advances in hepatobiliary techniques have improved the perioperative
      and long-term survival outcomes of this tumor.

PMID- 25376340
TI  - Internet claims on dietary and herbal supplements in advanced nephropathy: truth
      or myth.
AB  - BACKGROUND: The use of complementary/alternative medicine has garnered rising
      interest in recent years. Natural products including herbs, vitamins, and
      minerals are the most popularly consumed. The Internet is a ubiquitous source of
      information/market for these supplements. AIM: To systematically evaluate the
      dietary and herbal supplement recommended for patients with CKD and ESRD on the
      Internet, and try to distinguish between the claim of the manufacturer and proven
      scientific data. METHODS: A questionnaire assessing each website was formulated.
      Each product ingredient was recorded in the questionnaire by two independent
      reviewers and statistically analyzed. RESULTS: Of the 184 websites, 28% claimed
      to decrease CKD progression, 60% did not advise to consult a doctor before taking
      the supplement, and >90% did not mention any potential drug interaction, disease
      interaction, or caution in use during pregnancy or in children. The ten common
      plant ingredients claiming to be beneficial in kidney diseases were uva ursi,
      dandelion, parsley, corn silk, juniper, celery, buchu, horsetail, marshmallow,
      and stinging nettle. In contrast to their claims, these substances were not
      adequately studied in humans. The available animal studies showed detrimental
      effects and potential drug interactions with commonly used medications in the
      CKD/ESRD population. CONCLUSIONS: Nephrologists need to be cognizant of the lack
      of substantiated proven benefits of these substances and of the potential adverse
      effects in the animal models that can translate to the patients. Most
      importantly, the policy needs to change regarding the regulation of these
      products to prevent patient harm and misinformation.

PMID- 25376339
TI  - Low-dose mercury heightens early innate response to coxsackievirus infection in
      female mice.
AB  - OBJECTIVE: Mercury is a ubiquitous environmental contaminant with toxic outcomes
      over a range of exposures. In this study, we investigated the effects of mercury
      exposure on early immune responses to coxsackievirus B3 (CVB3) infection in a
      murine model of autoimmune heart disease. MATERIALS AND METHODS: Female BALB/c
      mice, susceptible to CVB3-induced autoimmune myocarditis, were treated with
      mercuric chloride (200 MUg/kg body weight every other day for 2 weeks) prior to
      infection with CVB3. Six hours post-infection, immune cells were isolated from
      the spleen and peritoneum for flow cytometry, gene expression, and cytokine
      profiling. Thirty-five days post-infection, hearts were collected for
      histological examination of immune cell infiltration. RESULTS: As for male mice,
      mercury exposure significantly increased autoimmune myocarditis and immune
      infiltration into the heart. During the innate response 6 h post-infection,
      mercury increased expression of co-stimulatory molecules and innate immune
      receptors on peritoneal macrophages. At the same time point, the alternatively
      activated macrophage gene, arginase, was increased while the classically
      activated macrophage gene, inducible nitric oxide synthase, was unaffected.
      Expression of activation markers were decreased on peritoneal B cells with
      mercury exposure while T cells were unaffected. Mercury increased production of
      pro-inflammatory mediators in the spleen. Macrophage-recruiting chemokines and
      activating cytokines, such as CCL2, CCL4, and IL-6, were increased with mercury
      following CVB3 infection. CONCLUSIONS: Thus, mercury treatment exacerbates
      autoimmune myocarditis in female mice and alters early innate signaling on
      peritoneal macrophages. Mercury also modulates the cytokine profile in the spleen
      toward a macrophage-activating milieu, and upregulates alternatively activated
      macrophage genes, providing evidence that mercury exposure promotes inflammation
      in the context of infection.

PMID- 25376338
TI  - Role of farnesoid X receptor in inflammation and resolution.
AB  - OBJECTIVE: The aim of this paper is to review the developments of farnesoid X
      receptor (FXR) biology, its ligands, and various functions, in particular we
      discuss the anti-inflammatory and anti-fibrotic role in chronic inflammatory
      diseases. INTRODUCTION: FXR is a ligand-dependent transcription factor belonging
      to the nuclear hormone receptor superfamily. The accrued data have shown that the
      FXR plays important roles not only in bile acid, lipid metabolism, and
      carbohydrate homeostasis, but also in inflammatory responses. The anti
      inflammatory and anti-fibrotic effects of FXR on chronic inflammatory diseases
      are not well documented. METHODS: A literature survey was performed using PubMed
      database search to gather complete information regarding FXR and its role in
      inflammation. RESULTS AND DISCUSSION: FXR is highly expressed in liver,
      intestine, kidney and adrenals, but with lower expression in fat tissue, heart
      and recently it has been found to express in lungs too. Primary bile acids,
      cholic acid and chenodeoxycholic acid are the natural endogenous ligands for FXR.
      GW4064 and 6alpha-ethyl-chenodeoxycholic acid are the synthetic high-affinity
      agonists. An exhaustive literature survey revealed that FXR acts as a key
      metabolic regulator and potential drug target for many metabolic syndromes that
      include chronic inflammatory diseases.

PMID- 25376341
TI  - Long-term prognoses and outcomes of axillary lymph node recurrence in 2,578
      sentinel lymph node-negative patients for whom axillary lymph node dissection was
      omitted: results from one Japanese hospital.
AB  - BACKGROUND: Axillary dissection omission for sentinel lymph node-negative
      patients has been a practice at Cancer Institute Hospital, Japanese Foundation
      for Cancer Research since 2003. We examined the long-term results of omission of
      axillary dissection in sentinel lymph node-negative patients treated at our
      hospital, as well as their axillary lymph node recurrence characteristics and
      outcomes. METHODS: Our study included 2,578 patients with cTis or T1-T3N0M0
      primary breast cancer for whom dissection was omitted because they were sentinel
      lymph node negative. The median observation period was 75 months. RESULTS: In
      sentinel lymph node-negative patients for whom dissection was omitted, the rates
      of axillary lymph node recurrence, distant recurrence, and breast cancer
      mortality were 0.9, 2, and 1 %, respectively. Eighteen patients underwent
      additional dissection if axillary lymph node recurrence was observed at the first
      recurrence. Four triple-negative (TN) patients experienced distant recurrence
      after additional dissection. All four patients were administered anticancer
      agents after axillary lymph node recurrence and experienced recurrence within 1
      year of additional dissection. The axillary lymph node recurrence rate was 0.8 %
      for luminal and 4.5 % for TN subtypes. CONCLUSIONS: The long-term prognoses of
      patients for whom dissection was omitted owing to negative sentinel lymph node
      metastases were similar to those reported previously-low recurrence and mortality
      rates. The frequency of axillary lymph node recurrence and the post-recurrence
      outcome differed between luminal and TN cases, with recurrence being more
      frequent in patients with the TN subtype. TN patients also had poorer prognoses,
      even after receiving additional dissection and anticancer agents after
      recurrence.

PMID- 25376342
TI  - Communication gaps associated with donor-derived infections.
AB  - The detection and management of potential donor-derived infections is
      challenging, in part due to the complexity of communications between diverse
      labs, organ procurement organizations (OPOs), and recipient transplant centers.
      We sought to determine if communication delays or errors occur in the reporting
      and management of donor-derived infections and if these are associated with
      preventable adverse events in recipients. All reported potential donor-derived
      transmission events reviewed by the Organ Procurement and Transplantation Network
      Ad Hoc Disease Transmission Advisory Committee from January 2008 to June 2010
      were evaluated for communication gaps between the donor center, OPO and
      transplant centers. The impact on recipient outcomes was then determined. Fifty
      six infection events (IEs; involving 168 recipients) were evaluated. Eighteen IEs
      (48 recipients) were associated with communication gaps, of which 12 resulted in
      adverse effects in 69% of recipients (20/29), including six deaths. When IEs and
      test results were reported without delay, appropriate interventions were taken,
      subsequently minimizing or averting recipient infection (23 IEs, 72 recipients).
      Communication gaps in reported IEs are frequent, occur at multiple levels in the
      communication process, and contribute to adverse outcomes among affected
      transplant recipients. Conversely, effective communication minimized or averted
      infection in transplant recipients. 

PMID- 25376343
TI  - Viral CD8 T cell epitope nucleotide composition shows evidence of short- and long
      term evolutionary strategies.
AB  - Viral epitopes have a distinct codon usage that reflects their dual role in
      infection and immunity. On the one hand, epitopes are part of proteins important
      to viral function; on the other hand, they are targets of the immune response.
      Studies of selection are most commonly based on changes of amino acid and seen
      through the accumulation of non-synonymous mutations. An independent measure of
      selection is the codon usage and underlying changeability of the nucleotide
      sequences. We here use multiple tools and a large-scale analysis of viral genomes
      to demonstrate that viral epitopes have a distinct codon usage and that this
      codon usage reflects distinct short- and long-term types of selection during
      viral evolution. We show that CD8(+) T cell epitopes are encoded by codons more
      distant from stop codons and more changeable than codons outside epitopes. This
      biased codon usage reflects the viral population toggling back and forth from a
      wild-type sequence to an escape mode, which enable them to avoid immune detection
      when needed, and go back to the functionally favorable form when the threat is
      removed (i.e., in a new host). 

PMID- 25376345
TI  - Transitional objects and thumb sucking.

PMID- 25376344
TI  - Density-dependent movement and the consequences of the Allee effect in the model
      organism Tetrahymena.
AB  - Movement and dispersal are critical processes for almost all organisms in natural
      populations. Understanding their causes and consequences is therefore of high
      interest. While both theoretical and empirical work suggest that dispersal, more
      exactly emigration, is plastic and may be a function of local population density,
      the functional relationship between the underlying movement strategies and
      population density has received less attention. We here present evidence for the
      shape of this reaction norm and are able to differentiate between three possible
      cues: the relative number of individuals, the presence of metabolites (chemical
      cues) and resource availability. We performed microcosm experiments with the
      ciliate model organism Tetrahymena in order to understand the plasticity of
      movement strategies with respect to local density while controlling for possible
      confounding effects mediated by the availability of different cues. In addition,
      we investigated how an Allee effect can influence movement and dispersal
      plasticity. Our findings suggest that movement strategies in Tetrahymena are
      plastic and density-dependent. The observed movement reaction norm was U-shaped.
      This may be due to an Allee effect which led to negative density dependence at
      low population densities and generally positive density dependence at high
      population densities due to local competition. This possibly adaptive density
      dependent movement strategy was likely mediated by chemical cues. Our
      experimental work in highly controlled conditions indicates that both
      environmental cues as well as inherent population dynamics must be considered to
      understand movement and dispersal. 

PMID- 25376346
TI  - Paediatric short case examination.
AB  - The short case is a highly artificial scenario, in which the examination
      candidate is given little or no history and instructed to examine one system or
      one aspect of a patient and draw conclusions. Despite their artificiality, short
      cases test clinical skills which senior paediatricians value and consider
      essential qualities of a competent physician. This article presents some general
      suggestions on an approach to doing short case examinations. 

PMID- 25376347
TI  - Pulse oximetry screening of newborns: not just a screening test for congenital
      heart disease.

PMID- 25376352
TI  - An 11-year-old with a tongue twister.

PMID- 25376353
TI  - Convulsions and erythematous linear verrucous lesions.

PMID- 25376354
TI  - The importance of physical examination in patients with mental health
      presentations.

PMID- 25376355
TI  - Antibiotic prescribing in the paediatric emergency department and the impact of
      education.

PMID- 25376356
TI  - Case of infantile onychomycosis successfully cured by 5% amorolfine nail lacquer.

PMID- 25376360
TI  - Fatty liver indices in the multiethnic United States National Health and
      Nutrition Examination Survey.
AB  - BACKGROUND: Validated non-invasive measures of fatty liver are needed that can be
      applied across populations and over time. A fatty liver index (FLI) including
      body mass index, waist circumference, triglycerides and gamma glutamyltransferase
      (GGT) activity was developed in an Italian municipality, but has not been
      validated widely or examined in a multiethnic population. AIMS: We evaluated this
      FLI in the multiethnic U.S. National Health and Nutrition Examination Survey
      (NHANES) and also to explore whether an improved index for the U.S. population
      (US FLI) could be derived. The US FLI would then used to examine U.S. time trends
      in fatty liver prevalence. METHODS: We studied 5869 fasted, viral hepatitis
      negative adult participants with abdominal ultrasound data on fatty liver in the
      1988-1994 NHANES. Time trend analyses included 21 712 NHANES 1988-1994 and 1999
      2012 participants. RESULTS: The prevalence of fatty liver was 20%. For the FLI,
      the area under the receiver operating characteristic curve [AUC; 95% confidence
      interval (CI)] was 0.78 (0.74-0.81). The US FLI included age, race-ethnicity,
      waist circumference, GGT activity, fasting insulin and fasting glucose and had an
      AUC (95% CI) of 0.80 (0.77-0.83). Defining fatty liver as a US FLI >= 30, the
      prevalence increased from 18% in 1988-1991 to 29% in 1999-2000 to 31% in 2011
      2012. CONCLUSIONS: For predicting fatty liver, the US FLI was a modest
      improvement over the FLI in the multiethnic U.S. population. Using this measure,
      the fatty liver prevalence in the U.S. population increased substantially over
      two decades.

PMID- 25376361
TI  - Evaluation of the DDAVP test in the diagnosis of Cushing's Disease.
AB  - OBJECTIVE: To analyse the performance of the desmopressin (DDAVP) test in the
      diagnosis of Cushing's disease (CD). METHODS: This was a prospective cohort study
      of 124 patients with suspected hypercortisolism who were recruited from an
      outpatient endocrinology clinic and investigated for Cushing's syndrome (CS). The
      ACTH and cortisol responses to the DDAVP test were assessed to determine patient
      diagnosis and test the procedure's diagnostic accuracy. RESULTS: A total of 68
      patients had CD, while 56 had suspected CS. According to ROC analysis, an ACTH
      peak of 71.8 pg/ml (15.8 pmol/l) following DDAVP administration was able to
      diagnose CD with a specificity of 94.6% and a sensitivity of 90.8%, a negative
      predictive value (NPV) of 89.9% and a positive predictive value (PPV) of 95.3%.
      An absolute ACTH increment >=37 pg/ml (8.1 pmol/l) over baseline had a
      sensitivity of 88.0%, specificity of 96.4%, NPV of 87.0% and PPV of 95.3% in
      diagnosing CD. Only 2 of 56 cases without CD had an absolute ACTH increment >=37
      pg/ml (8.1 pmol/l) over baseline. The DDAVP test was superior to other clinical
      instruments in diagnosing CS. CONCLUSIONS: The DDAVP test could be a useful
      additional tool to diagnose CD in patients with suspected CS.

PMID- 25376362
TI  - The Shanghai Aging Study: study design, baseline characteristics, and prevalence
      of dementia.
AB  - BACKGROUND: To establish a prospective cohort to enumerate the prevalence,
      incidence and risk factors for dementia and mild cognitive impairment (MCI) among
      residents aged >=60 in an urban community of Shanghai, China. METHODS:
      Participants received clinical evaluations including physical measurements,
      demographic and lifestyle questionnaires, physical and neurologic examinations,
      and neuropsychological testing. Urine and blood samples were collected,
      aliquoted, and stored. DNA was extracted for Apolipoprotein (APOE) genotyping.
      Diagnoses of dementia and MCI were made using standard criteria via consensus
      diagnosis. RESULTS: Among 3,141 participants aged >=60, 1,438 (45.8%) were men.
      The average age of participants was 72.3 years (SD 8.1), and they had an average
      of 11.6 years (SD 4.4) of education. The most common chronic disease of
      participants was hypertension (56.4%). The frequencies of APOE-epsilon2, epsilon3
      and epsilon4 were 7.9, 82.7 and 9.4%, respectively. We diagnosed 156 (5.0%, 95%
      CI 4.3-5.8%) participants with dementia. The prevalence rates of Alzheimer's
      disease and vascular dementia were 3.6% (95% CI 3.0-4.3%) and 0.8% (95% CI 0.5
      1.1%). CONCLUSIONS: The Shanghai Aging Study is the first prospective community
      based cohort study of cognitive impairment in China, with a comparable study
      design, procedures, and diagnostic criteria for dementia and MCI to most previous
      cohort studies in developed countries.

PMID- 25376363
TI  - Do we really know the symptoms of inguinal hernia?
AB  - PURPOSE: Although there is a high incidence of inguinal hernia in developed
      countries, few studies have been conducted to describe the symptoms, and these
      few only address the local symptoms, not those presenting at other levels. The
      aim of the present study is to conduct a detailed review of the symptoms, both
      inguinal and otherwise, of patients with inguinal hernia. METHODS: A case-control
      study was designed to compare the symptoms presented by 231 patients diagnosed
      with inguinal hernia with those of a second group of 231 randomly-selected
      subjects. In the hernia group, the symptoms were also evaluated according to the
      location of the hernia (right, left, bilateral). RESULTS: Significant differences
      (more symptomatology in patients with hernia) were found for the following items:
      groin pain, genital pain, urinary symptoms, abdominal pain, increased peristalsis
      and tenesmus. On the contrary, the control patients presented greater
      symptomatology with respect to back pain and diaphragm pain. CONCLUSIONS:
      Patients with inguinal hernia present a wide variety of symptoms, and these are
      not restricted to the inguinal area. It is important to be aware of this fact to
      convey accurate information to the patient, especially with regard to
      postoperative expectations.

PMID- 25376366
TI  - Improvement of biomaterials used in tissue engineering by an ageing treatment.
AB  - Biomaterials based on crosslinked sponges of biopolymers have been extensively
      used as scaffolds to culture mammal cells. It is well known that single
      biopolymers show significant change over time due to a phenomenon called physical
      ageing. In this research, it was verified that scaffolds used for skin tissue
      engineering (based on gelatin, chitosan and hyaluronic acid) express an ageing
      like phenomenon. Treatments based on ageing of scaffolds improve the behavior of
      skin-cells for tissue engineering purposes. Physical ageing of dry scaffolds was
      studied by differential scanning calorimetry and was modeled with ageing kinetic
      equations. In addition, the physical properties of wet scaffolds also changed
      with the ageing treatments. Scaffolds were aged up to 3 weeks, and then skin
      cells (fibroblasts) were seeded on them. Results indicated that adhesion,
      migration, viability, proliferation and spreading of the skin-cells were affected
      by the scaffold ageing. The best performance was obtained with a 2-week aged
      scaffold (under cell culture conditions). The cell viability inside the scaffold
      was increased from 60% (scaffold without ageing treatment) to 80%. It is
      concluded that biopolymeric scaffolds can be modified by means of an ageing
      treatment, which changes the behavior of the cells seeded on them. The ageing
      treatment under cell culture conditions might become a bioprocess to improve the
      scaffolds used for tissue engineering and regenerative medicine.

PMID- 25376365
TI  - Early retesting by GHRH + arginine test shows normal GH response in most children
      with idiopathic GH deficiency.
AB  - PURPOSE: Most children with idiopathic isolated GH deficiency (IGHD) normalize GH
      response to stimulation tests when retested at the completion of growth. The
      objective of this study was to test the effectiveness of early retesting in
      challenging the diagnosis of idiopathic IGHD and critically review the diagnostic
      workup leading to this diagnosis in children with short stature. METHODS: We
      cross-sectionally retested 38 children with idiopathic IGHD and still on GH
      treatment. The initial diagnosis of idiopathic IGHD was based on subnormal GH
      responses to two stimulation tests and normal brain imaging or minor/nonspecific
      findings at magnetic resonance. The GH response normalization at retesting was
      considered as the main outcome measure. Clinical features of children who were
      falsely classified as idiopathic IGHD based on first GH testing were
      retrospectively analyzed. RESULTS: GH secretion was normal in 36/38 children
      (95%). Two children showed slightly reduced peak GH responses and normal IGF-I
      levels. Fourteen children underwent GH retesting before puberty, 24 children
      during puberty. CONCLUSION: The diagnostic process should be improved to minimize
      the rate of false positive at GH testing and, in case of unsatisfactory response
      to GH treatment, the diagnosis of isolated idiopathic GHD should be challenged
      with early retesting.

PMID- 25376368
TI  - Editorial comment to Human papillomavirus-related basaloid squamous cell
      carcinoma of the bladder associated with genital tract human papillomavirus
      infection.

PMID- 25376367
TI  - Construction of malate-sensing Escherichia coli by introduction of a novel
      chimeric two-component system.
AB  - In an attempt to develop a high-throughput screening system for screening
      microorganisms which produce high amounts of malate, a MalKZ chimeric HK-based
      biosensor was constructed. Considering the sequence similarity among Escherichia
      coli (E. coli) MalK with Bacillus subtilis MalK and E. coli DcuS, the putative
      sensor domain of MalK was fused with the catalytic domain of EnvZ. The chimeric
      MalK/EnvZ TCS induced the ompC promoter through the cognate response regulator,
      OmpR, in response to extracellular malate. Real-time quantitative PCR and GFP
      fluorescence studies showed increased ompC gene expression and GFP fluorescence
      as malate concentration increased. By using this strategy, various chimeric TCS
      based bacteria biosensors can be constructed, which may be used for the
      development of biochemical-producing recombinant microorganisms. 

PMID- 25376369
TI  - Outcomes following emergent open repair for thoracic aortic dissection are
      improved at higher volume centers.
AB  - BACKGROUND: Previous studies have demonstrated that patients undergoing complex
      surgical procedures at high-volume centers have improved outcomes. The goal of
      this study was to determine if this volume-outcomes relationship persists at a
      national level among patients undergoing emergent open repair for thoracic aortic
      dissection. METHODS: De-identified patient-level data were obtained from the
      Nationwide Inpatient Sample (2005 to 2008). Patients undergoing emergent aortic
      surgery for thoracic aortic dissection (n = 1230) were identified by ICD-9 codes
      and stratified by annual center volume into low volume (<=5 cases/year),
      intermediate volume (6 to 10 cases/year), and high volume (>=11 cases/year). The
      Deyo-Charlson co-morbidity score was used to adjust for differences in
      comorbidity between groups. Major outcomes of interest included: in-hospital
      morbidity and mortality, length of hospitalization, total hospital costs, and
      discharge disposition. RESULTS: There was a significant association between in
      hospital mortality and center volume (p = 0.014), with low, intermediate, and
      high-volume centers having mortality rates of 23.4% (n = 187), 20.1% (n = 62),
      and 12.1% (n = 15), respectively. This relationship persisted when controlling
      for severity of co-morbid illness (p = 0.007). The number of complications per
      patient varied significantly by center volume (p = 0.044), with a higher
      proportion of patients at high-volume centers having no complications. Also, the
      highest proportion of home discharges was observed among patients at high-volume
      centers (p = 0.011). CONCLUSIONS: Survival following emergent open repair for
      thoracic aortic dissection was significantly greater at high-volume centers.
      These findings suggest that understanding the processes at high-volume centers
      that underlie this volume-outcomes relationship may improve in-hospital survival
      and postoperative complications.

PMID- 25376364
TI  - Rare diseases in clinical endocrinology: a taxonomic classification system.
AB  - PURPOSE: Rare endocrine-metabolic diseases (REMD) represent an important area in
      the field of medicine and pharmacology. The rare diseases of interest to
      endocrinologists involve all fields of endocrinology, including rare diseases of
      the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis,
      disorders of bone and mineral metabolism, energy and lipid metabolism, water
      metabolism, and syndromes with possible involvement of multiple endocrine glands,
      and neuroendocrine tumors. Taking advantage of the constitution of a study group
      on REMD within the Italian Society of Endocrinology, consisting of basic and
      clinical scientists, a document on the taxonomy of REMD has been produced.
      METHODS AND RESULTS: This document has been designed to include mainly REMD
      manifesting or persisting into adulthood. The taxonomy of REMD of the adult
      comprises a total of 166 main disorders, 338 including all variants and subtypes,
      described into 11 tables. CONCLUSIONS: This report provides a complete taxonomy
      to classify REMD of the adult. In the future, the creation of registries of rare
      endocrine diseases to collect data on cohorts of patients and the development of
      common and standardized diagnostic and therapeutic pathways for each rare
      endocrine disease is advisable. This will help planning and performing
      intervention studies in larger groups of patients to prove the efficacy,
      effectiveness, and safety of a specific treatment.

PMID- 25376370
TI  - Roles of glucose transporter-1 and the phosphatidylinositol 3-kinase/protein
      kinase B pathway in cancer radioresistance (review).
AB  - The mechanisms underlying cancer radioresistance remain unclear. Several studies
      have found that increased glucose transporter-1 (GLUT-1) expression is associated
      with radioresistance. Recently, the phosphatidylinositol 3-kinase (PI3K)/protein
      kinase B (Akt) pathway was reported to be involved in the control of GLUT-1
      trafficking and activity. Activation of the PI3K/Akt pathway may itself be
      associated with cancer radioresistance. Thus, increasing attention has been
      devoted to the effects of modifying the expression of GLUT-1 and the PI3K/Akt
      pathway on the increase in the radiosensitivity of cancer cells. This review
      discusses the importance of the association between elevated expression of GLUT-1
      and activation of the PI3K/Akt pathway in the development of radioresistance in
      cancer.

PMID- 25376371
TI  - Electricity-driven metabolic shift through direct electron uptake by
      electroactive heterotroph Clostridium pasteurianum.
AB  - Although microbes directly accepting electrons from a cathode have been applied
      for CO2 reduction to produce multicarbon-compounds, a high electron demand and
      low product concentration are critical limitations. Alternatively, the
      utilization of electrons as a co-reducing power during fermentation has been
      attempted, but there must be exogenous mediators due to the lack of an
      electroactive heterotroph. Here, we show that Clostridium pasteurianum DSM 525
      simultaneously utilizes both cathode and substrate as electron donors through
      direct electron transfer. In a cathode compartment poised at +0.045 V vs. SHE, a
      metabolic shift in C. pasteurianum occurs toward NADH-consuming metabolite
      production such as butanol from glucose (20% shift in terms of NADH consumption)
      and 1,3-propandiol from glycerol (21% shift in terms of NADH consumption).
      Notably, a small amount of electron uptake significantly induces NADH-consuming
      pathways over the stoichiometric contribution of the electrons as reducing
      equivalents. Our results demonstrate a previously unknown electroactivity and
      metabolic shift in the biochemical-producing heterotroph, opening up the
      possibility of efficient and enhanced production of electron-dense metabolites
      using electricity. 

PMID- 25376372
TI  - Pharmacokinetic-pharmacodynamic modeling for reduction of hepatic apolipoprotein
      B mRNA and plasma total cholesterol after administration of antisense
      oligonucleotide in mice.
AB  - Second-generation antisense oligonucleotides (ASOs) demonstrate excellent
      biological stability and in vitro/in vivo potency, and thus are considered to be
      attractive candidates for drugs to treat various diseases. A pharmacokinetic
      pharmacodynamic (PK-PD) model of ASOs is desired for the design of appropriate PK
      and pharmacological studies. The objective of this study was to develop a PK-PD
      model to accurately simulate hepatic ASO concentration and its efficacy from
      plasma ASO concentration. After single subcutaneous administration of an ASO
      targeting hepatic apolipoprotein B (Apo-B) mRNA to mice, the ASO was absorbed
      rapidly and showed biphasic decline with time from the plasma and liver (t1/2: 1
      3 and 81-183 h, Tmax: 0.25-0.50 and 4-8 h). After administration, hepatic Apo-B
      mRNA and plasma total cholesterol began decreasing at 4-8 and 8-24 h, and their
      Tmax values were observed at 24-72 and 72 h. To develop the PK-PD model based on
      the mechanisms of ASOs, we described the plasma and hepatic ASO concentration
      with linear two-compartment models. In addition, we inserted two indirect
      response models for mRNA and plasma total cholesterol. Model predictions from
      plasma ASO concentration gave excellent fits to the observed values of hepatic
      ASO concentration, Apo-B mRNA and plasma total cholesterol after single or
      multiple subcutaneous administrations. Our PK-PD model could accurately predict
      hepatic ASO concentrations and their efficacies from plasma ASO concentrations.
      This PK-PD model could be a useful tool for suggesting PK and pharmacological
      study protocols for various liver-targeted second-generation ASOs. 

PMID- 25376375
TI  - Urine drug screening: necessary or alienating?

PMID- 25376373
TI  - Hypoxia-induced p38 MAPK activation reduces Mcl-1 expression and facilitates
      sensitivity towards BH3 mimetics in chronic lymphocytic leukemia.

PMID- 25376376
TI  - Psychosurgery for schizophrenia.

PMID- 25376374
TI  - A comparative assessment of the curative potential of reduced intensity
      allografts in acute myeloid leukaemia.
AB  - Allogeneic stem cell transplantation (SCT) provides the best mechanism of
      preventing relapse in acute myeloid leukaemia (AML). However non-relapse
      mortality (NRM) negates this benefit in older patients. Reduced intensity
      conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure is
      uncertain. In the MRC AML15 Trial, patients in remission without favourable risk
      disease could receive SCT from a matched sibling or unrelated donor (MUD). If
      aged >45 years, a RIC was recommended and in patients aged 35-44 years, either
      RIC or myeloablative conditioning was permitted. The aim was to determine which
      approach improved survival and within which prespecified cytogenetic groups. RIC
      transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50
      0.85), P=0.002) compared to chemotherapy The 5-year overall survival from a
      sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01-2.21),
      P=0.04) due to lower NRM (34 vs 14%, P=0.002) In adjusted analyses, there was a
      survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57
      0.97), P=0.03), with consistent results in intermediate and adverse-risk
      patients. In patients aged 35-44 years, best outcomes were seen with a sibling
      RIC transplant, although a comparison with chemotherapy and myeloablative
      transplant was not significant in adjusted analyses (P=0.3). 

PMID- 25376377
TI  - Practical utility of insulin-like growth factor II mRNA-binding protein 3,
      glucose transporter 1, and epithelial membrane antigen for distinguishing
      malignant mesotheliomas from benign mesothelial proliferations.
AB  - The differentiation of malignant mesotheliomas and benign mesothelial
      proliferations is crucial in determining patient care and prognosis. But, this
      distinction can be extremely difficult, particularly in small biopsies. Recently,
      insulin-like growth factor II mRNA-binding protein 3 (IMP3) and glucose
      transporter 1 (GLUT-1) have been reported as specific and sensitive markers in
      the distinction of mesotheliomas from benign mesothelial proliferations. The
      purpose of this study is to evaluate the utility of IMP3, GLUT-1, and epithelial
      membrane antigen (EMA) immunohistochemistry for distinguishing mesotheliomas from
      benign mesothelial proliferations. Immunoexpression of IMP3, GLUT-1, and EMA was
      evaluated in 88 malignant mesotheliomas, 35 adenomatoid tumors, and 20 benign
      lung tissues with reactive mesothelial cells. The sensitivity for IMP3, GLUT-1,
      and EMA was 37%, 21%, and 41%, respectively. The specificity for IMP3, GLUT-1,
      and EMA was 100%. When IMP3, GLUT1, and EMA combined, the sensitivity was 66% for
      IMP3/EMA staining, 53% for GLUT-1/EMA staining, and 45% for IMP3/GLUT-1. Use of
      IMP3 and EMA together is more helpful to distinguish malignant mesotheliomas from
      benign mesothelial proliferations than the use of IMP3 or EMA alone. 

PMID- 25376378
TI  - Quality of life changes and intensive care preferences in terminal cancer
      patients.
AB  - OBJECTIVE: There is scarce research on the short-term fluctuations in end-of-life
      (EoL) care planning for seriously ill patients. The aim of our study was to
      investigate the stability of preferences regarding treatment in an intensive care
      unit (ICU) and identify the factors associated with changes in preferences in
      terms of quality of life (QoL). METHOD: A prospective examination on preference
      changes for ICU care in 141 terminal cancer patients was conducted. Patients were
      categorized according to their change in preference during the final two months
      of their lives into four categories: (1) the keep-accept group, (2) the keep
      reject group, (3) the change to accept group, and (4) the change to reject group.
      Using multiple logistic analyses, we explored the association between patient
      demographics, health-related QoL, and changes in ICU preference. RESULTS: The
      overall stability of ICU preferences near the end of life was 66.7% (kappa =
      0.33, p < 0.001). Married patients were more likely to change their preference
      regarding ICU care [adjusted odds ratio (aOR) toward accept 12.35, p = 0.021; aOR
      toward reject 10.56, p = 0.020] than unmarried patients. Patients with stable
      physical function tended to accept ICU care (aOR = 5.05, p = 0.023), whereas
      those with poor performance (aOR = 5.32, p = 0.018), worsened QoL (aOR = 8.34, p
      = 0.007), or non-aggravated fatigue (aOR = 8.36, p = 0.006) were more likely to
      not accept ICU care. SIGNIFICANCE OF RESULTS: The attitudes of terminally ill
      cancer patients regarding ICU care at the end of life were not stable over time,
      and changes in their QoL were associated with a tendency to change their
      preferences about ICU care. Attention should thus be paid to patients' QoL
      changes to improve medical decision making with regard to EoL care.

PMID- 25376379
TI  - The Arctic mutation accelerates Abeta aggregation in SDS through reducing the
      helical propensity of residues 15-25.
AB  - Mutations within the beta-amyloid peptide (Abeta) sequence that cause early onset
      familial Alzheimer's disease (FAD) have been shown to promote Abeta aggregation.
      How these FAD-related mutants increase the aggregative ability of Abeta is not
      fully understood. Here, we characterized the effect of the Arctic variant (E22G)
      on the conformational stability of Abeta using various forms of spectroscopy and
      kinetic analyses, including nuclear magnetic resonance (NMR), circular dichroism
      (CD) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy and
      transmission electron microscopy (TEM). The E22G mutation in the Arctic variant
      reduced the alpha-helical propensity and conformational stability of Abeta on
      residues 15-25. This mutation also caused an increase in both alpha-helix-to-beta
      strand conversion and fibril nucleation rates. Our results suggest that the alpha
      helical propensity of residues 15-25 may play a determinant role in the
      aggregative ability of Abeta. This may provide a structural basis for
      understanding the molecular mechanism of Abeta aggregation. 

PMID- 25376380
TI  - Risk factors for AA amyloidosis in Germany.
AB  - OBJECTIVE: To identify risk factors for serum amyloid-A (AA) amyloidosis in
      patients living in Germany. METHODS: Clinical and genetic data were obtained from
      71 patients with AA amyloidosis. SAA1 genotypes were analyzed in 231 individuals.
      Control groups comprised 45 patients with long-standing inflammatory diseases
      without AA amyloidosis and 56 age-matched patients without any inflammatory
      disease. RESULTS: The most frequent underlying diseases of AA amyloidosis were
      familial Mediterranean fever (FMF) (n = 24, 34%) and inflammatory rheumatic
      diseases (n = 30, 42%). Patients without any known underlying disease (n = 11,
      16%) were considered as having idiopathic AA amyloidosis. Patients with FMF were
      significantly younger at disease onset and younger at diagnosis of AA amyloidosis
      compared with patients with rheumatic diseases. Patients with idiopathic AA
      amyloidosis were older than patients with definite rheumatic diseases. Patients
      with FMF and high penetrance MEFV gene mutations had a relative risk of 1.73 for
      AA amyloidosis. Patients with FMF or a rheumatic disease and the SAA1 alpha/alpha
      genotype had a relative risk of 4.86 and 2.53, respectively, for developing an AA
      amyloidosis. The prevalence of this risk genotype was 36% in German patients
      without an inflammatory disease, 92% in German patients with AA amyloidosis and
      100% in German patients with idiopathic AA amyloidosis. CONCLUSIONS: Risk factors
      for AA amyloidosis are the presence of a hereditary autoinflammatory or chronic
      rheumatic disease, elevated C-reactive protein and SAA serum levels, a long delay
      of a sufficient therapy, an advanced age and the SAA1alpha/alpha genotype.

PMID- 25376381
TI  - Characterisation of the ex vivo virulence of Leishmania infantum isolates from
      Phlebotomus perniciosus from an outbreak of human leishmaniosis in Madrid, Spain.
AB  - BACKGROUND: Since mid 2009, an outbreak of human leishmaniosis in Madrid, Spain,
      has involved more than 560 clinical cases. Many of the cases occurred in people
      who live in areas around a newly constructed green park (BosqueSur). This
      periurban park provides a suitable habitat for sand flies (the vectors of
      Leishmania infantum). Indeed, studies of blood meals from sand flies captured in
      the area showed a strong association between the insect vector, hares or rabbits,
      and humans in the area. Interestingly, up to 70% of cases have been found in
      immunocompetent patients (aged between 46-60 years). This study was designed to
      evaluate the ex vivo virulence of the L. infantum isolates from Phlebotomus
      perniciosus captured in this area of Madrid. METHODS: Murine macrophages and
      dendritic cells were infected ex vivo with L. infantum strain BCN150, isolate
      BOS1FL1, or isolate POL2FL7. At different times after infection, the infection
      indices, cytokine production (IL-12p40 and IL-10), NO release and arginase
      activities were evaluated. RESULTS: Using an ex vivo model of infection in murine
      bone marrow-derived cells, we found that infection with isolates BOS1FL1 and
      POL2FL7 undermined host immune defence mechanisms in multiple ways. The main
      factors identified were changes in both the balance of iNOS versus arginase
      activities and the equilibrium between the production of IL-12 and IL-10.
      Infection with isolates BOS1FL1 and POL2FL7 also resulted in higher infection
      rates compared to the BCN150 strain. Infection index values at 24 h were as
      follows: BCN150-infected cells, 110 for infected MO and 115 for infected DC;
      BOS1FL1-infected cells, 300 for infected MO and 247 for infected DC; and POL2FL7
      infected cells, 275 for infected MO and 292 for infected DC. CONCLUSIONS: Our
      data indicate that L. infantum isolates captured from this endemic area exhibited
      high virulence in terms of infection index, cytokine production and enzymatic
      activities involved in the pathogenesis of visceral leishmaniosis. Altogether,
      these data provide a starting point for the study of the virulence behaviour of
      parasites (BOS1FL1 and POL2FL7) isolated from P. perniciosus during the outbreak
      of human leishmaniosis in Madrid, Spain, and their involvement in infecting
      immunocompetent hosts.

PMID- 25376382
TI  - Multimodal therapy in treatment of rectal cancer is associated with improved
      survival and reduced local recurrence - a retrospective analysis over two
      decades.
AB  - BACKGROUND: The management of rectal cancer (RC) has substantially changed over
      the last decades with the implementation of neoadjuvant chemoradiotherapy,
      adjuvant therapy and improved surgery such as total mesorectal excision (TME). It
      remains unclear in which way these approaches overall influenced the rate of
      local recurrence and overall survival. METHODS: Clinical, histological and
      survival data of 658 out of 662 consecutive patients with RC were analyzed for
      treatment and prognostic factors from a prospectively expanded single
      institutional database. Findings were then stratified according to time of
      diagnosis in patient groups treated between 1993 and 2001 and 2002 and 2010.
      RESULTS: The study population included 658 consecutive patients with rectal
      cancer between 1993 and 2010. Follow up data was available for 99.6% of all 662
      treated patients. During the time period between 2002 and 2010 significantly more
      patients underwent neoadjuvant chemoradiotherapy (17.6% vs. 60%) and adjuvant
      chemotherapy (37.9% vs. 58.4%). Also, the rate of reported TME during surgery
      increased. The rate of local or distant metastasis decreased over time, and tumor
      related 5-year survival increased significantly with from 60% to 79%. CONCLUSION:
      In our study population, the implementation of treatment changes over the last
      decade improved the patient's outcome significantly. Improvements were most
      evident for UICC stage III rectal cancer.

PMID- 25376383
TI  - Primary care priorities in addressing health equity: summary of the WONCA 2013
      health equity workshop.
AB  - BACKGROUND: Research consistently shows that gaps in health and health care
      persist, and are even widening. While the strength of a country's primary health
      care system and its primary care attributes significantly improves populations'
      health and reduces inequity (differences in health and health care that are
      unfair and unjust), many areas, such as inequity reduction through the provision
      of health promotion and preventive services, are not explicitly addressed by
      general practice. Substantiating the role of primary care in reducing inequity as
      well as establishing educational training programs geared towards health inequity
      reduction and improvement of the health and health care of underserved
      populations are needed. METHODS: This paper summarizes the work performed at the
      World WONCA (World Organization of National Colleges and Academies of Family
      Medicine) 2013 Meetings' Health Equity Workshop which aimed to explore how a
      better understanding of health inequities could enable primary care providers
      (PCPs)/general practitioners (GPs) to adopt strategies that could improve health
      outcomes through the delivery of primary health care. It explored the development
      of a health equity curriculum and opened a discussion on the future and potential
      impact of health equity training among GPs. RESULTS: A survey completed by
      workshop participants on the current and expected levels of primary care
      participation in various inequity reduction activities showed that promoting
      access (availability and coverage) to primary care services was the most
      important priority. Assessment of the gaps between current and preferred
      priorities showed that to bridge expectations and actual performance, the
      following should be the focus of governments and health care systems: forming
      cross-national collaborations; incorporating health equity and cultural
      competency training in medical education; and, engaging in initiation of advocacy
      programs that involve major stakeholders in equity promotion policy making as
      well as promoting research on health equity. CONCLUSIONS: This workshop formed
      the basis for the establishment of WONCA's Health Equity Special Interest Group,
      set up in early 2014, aiming to bring the essential experience, skills and
      perspective of interested GPs around the world to address differences in health
      that are unfair, unjust, unnecessary but avoidable.

PMID- 25376384
TI  - Macrophage depletion ameliorates glycerol-induced acute kidney injury in mice.
AB  - BACKGROUND: This study was conducted to elucidate the role of renal macrophages
      in the development of acute kidney injury (AKI) in a glycerol (Gly)-induced
      rhabdomyolysis mouse model. METHODS: The experimental model of rhabdomyolysis
      requires injecting 50% Gly (10 ml/kg) intramuscularly into mice. Control mice
      were injected into the tail vein with the liposomal vehicle. Liposome
      encapsulated clodronate (LEC)-only mice were injected with LEC. Gly-only mice
      were injected with Gly into a hind limb. LEC+Gly-treated mice were injected
      intravenously with 100 MUl of LEC 24 h prior to Gly injection. Mice were
      sacrificed 24 h after Gly injection. RESULTS: Gly injection increased the serum
      creatinine level, and induced tubular damage. Renal CD45(+)CD11b(+)Ly6c(+) or
      CD45(+)CD11b(+)Ly6c(+)F4/80(+) macrophages were decreased by pretreatment with
      LEC in both normal and injured kidneys. Macrophage depletion prevented Gly
      induced apoptotic death of tubular epithelial cells by decreasing caspase-9, ERK
      and p53, while increasing Bcl-2 expression. Expression of the inflammatory
      mediators NF-kappaB, MCP-1, ICAM-1, iNOS and COX-2 were also decreased with LEC
      pretreatment of mice injected with Gly. CONCLUSION: These results support the
      hypothesis that depletion of macrophages prevents renal dysfunction by abrogating
      apoptosis and attenuating inflammation during AKI.

PMID- 25376385
TI  - Three-dimensional highly conductive graphene-silver nanowire hybrid foams for
      flexible and stretchable conductors.
AB  - Graphene foams have showed huge application potentials owing to their unique 3D
      structure and superior properties. Thus, it is highly desired to develop a simple
      and effective pathway to fabricate high performance graphene-based foams. Here,
      we present a polymer template-assisted assembly strategy for fabricating a novel
      class of graphene/AgNW hybrid foams. The hybrid foams show 3D ordered
      microstructures, high thermal stability, and excellent electrical and mechanical
      properties, and demonstrate huge application potential in the fields of flexible
      and stretchable conductors. Importantly, the polymer-template assisted assembly
      technique is simple, scalable, and low-cost, providing a new synthesis protocol
      for various multifunctional graphene hybrid foam-based composites. 

PMID- 25376387
TI  - Ligand replacement induced chemiluminescence for selective detection of an
      organophosphorus pesticide using bifunctional Au-Fe3O4 dumbbell-like
      nanoparticles.
AB  - A facile ligand replacement induced chemiluminescence method is developed for
      selective detection of the organophosphorus pesticide parathion-methyl based on
      the use of bifunctional Au-Fe3O4 dumbbell-like nanoparticles to overcome the
      interference from coexisting substances in a real sample. 

PMID- 25376386
TI  - Spring viraemia of carp virus induces autophagy for necessary viral replication.
AB  - Outbreaks of spring viraemia of carp virus (SVCV) in several carp species and
      other cultivated fish can cause significant mortality and jeopardize the billion
      dollar worldwide fish industry. Spring viraemia of carp virus, also known as
      Rhabdovirus carpio, is a bullet-shaped RNA virus that enters and amplifies in
      gill epithelium and later spreads to internal organs. Young fish under stressed
      conditions (spring cold water, etc.) are more vulnerable to SVCV-induced
      lethality because of their lack of a mature immune system. Currently, the host
      response of SVCV remains largely unknown. Here, we observed that autophagy is
      activated in SVCV-infected epithelioma papulosum cyprini (EPC) cells. We
      demonstrated that the SVCV glycoprotein, rather than viral replication, activates
      the autophagy pathway. In addition, SVCV utilized the autophagy pathway to
      facilitate its own genomic RNA replication and to enhance its titres in the
      supernatants. Autophagy promoted the survival of SVCV-infected cells by
      eliminating damaged mitochondrial DNA generated during viral infection. We
      further showed that SVCV induces autophagy in EPC cells through the ERK/mTOR
      signalling pathway. Our results reveal a connection between autophagy and SVCV
      replication and propose autophagy suppression as a novel means to restrict SVCV
      viral replication. 

PMID- 25376388
TI  - Synthesis, structure and catalytic application of lead(II) complexes in
      cyanosilylation reactions.
AB  - Hydrothermal reactions of a lead(II) salt with 3-aminopyrazine-2-carboxylic acid
      (HL1) gave rise to a series of lead(II) coordination compounds (1-6) having zero,
      one, two and three dimensional structures. X-ray diffraction structural analyses
      reveal that complexes [Pb(L1)2]2 (1) and [Pb(L1)(OCHNH2)(eta-OCHO)]2 (2) possess
      dinuclear structures, containing a centre of symmetry. Complexes
      [Pb2(L1)4(NHMeCHO)2]n (3) and [Pb2(L1)4]n.(H2O)n.(2.5DMF)n (4) have 1D chain like
      structures, and [Pb5(L1)7(eta-NO3)(MU-HCOO)(eta-HCOO)]n.(DMF)n.(MeOH)n (5) shows
      a 2D sheet like structure constructed by the [Pb5O5(HCOO)] cluster and 3
      aminopyrazine-2-carboxylate anions. The hydrothermal reaction of lead(II) nitrate
      with HL1 in DMF led to in situ formation of 3,3'
      (methylenebis(azanediyl))bis(pyrazine-2-carboxylic acid) [H2L2] which produces
      the 3D framework [Pb2(L2)2]n.(2DMF)n.(H2O)n (6). The L1(-) and L2(2-) ligands
      bind the metal cations by means of a pyrazine N-atom and one, or both,
      carboxylate O-atoms. The carboxylate group of L1(-) presents a diversity of
      coordination modes, viz., monodentate (1 and 3), bridging MU2 (3) and bridging
      MU3 (4), monodentate bridging MU2 (1, 2, 4, 5 and 6) and bridging chelate MU2
      (5). The carboxylate moiety of L2(2-) in 6 binds the metal in a bridging MU2
      fashion. The Pb(II) ions display coordination numbers from 5 to 8 with hemi- or
      holodirected coordination environments. The Pb(II) complexes act as heterogeneous
      catalysts for the cyanosilylation reaction, at 15  degrees C, of different
      aldehydes with trimethylsilyl cyanide (TMSCN) and can be recycled at least three
      times without losing activity.

PMID- 25376389
TI  - Reduction of regulatory T cells by Mogamulizumab, a defucosylated anti-CC
      chemokine receptor 4 antibody, in patients with aggressive/refractory mycosis
      fungoides and Sezary syndrome.
AB  - PURPOSE: The CC chemokine receptor 4 (CCR4) is expressed on malignant T cells in
      cutaneous T-cell lymphoma (CTCL) as well as on regulatory T cells (Treg). When
      mogamulizumab, a defucosylated monoclonal antibody, binds to CCR4, it induces
      antibody-dependent cellular cytotoxicity against CCR4(+) malignant T cells. The
      goal of this study was to determine the effect of mogamulizumab on CCR4(+) Tregs
      in patients with CTCL. EXPERIMENTAL DESIGN: Peripheral blood of 24 patients with
      CTCL participating in a phase I/II trial was analyzed for CCR4 expression on
      different T-cell subsets by flow cytometry, before and after one course of
      mogamulizumab. The number and function of natural killer (NK) cells were also
      analyzed. Lesional biopsies were examined for CCR4, Foxp3, and CD16 expression by
      immunohistochemistry. RESULTS: Malignant T cells in peripheral blood were 20.8%
      100% positive for CCR4 at baseline. Fourteen patients who achieved a response in
      blood had high baseline CCR4 expression on malignant T cells. Tregs in blood were
      58.6% to 100% positive for CCR4 at baseline and showed decreased numbers and CCR4
      expression after treatment. CD8(+) T cells in blood were 3.2% to 23.2% positive
      for CCR4 at baseline and showed limited reduction of CCR4 expression with
      increased percentages of CD8(+) T cells after treatment. Of 14 patients tested
      for NK cells in blood, 10 showed increased percentages after treatment. Four of 6
      patients tested showed increased NK cell cytotoxicity. Sixteen of 18 patients who
      had CCR4(+) lymphocytes in baseline lesions showed decreased numbers after
      treatment. CONCLUSIONS: Mogamulizumab reduces levels of CCR4(+) malignant T cells
      and also CCR4(+) Tregs in patients with CTCL, which may in turn improve immune
      profiles. Clin Cancer Res; 21(2); 274-85. (c)2014 AACR.

PMID- 25376390
TI  - Toxoplasma gondii-induced neuronal alterations.
AB  - The zoonotic pathogen Toxoplasma gondii infects over 30% of the human population.
      The intracellular parasite can persist lifelong in the CNS within neurons
      modifying their function and structure, thus leading to specific behavioural
      changes of the host. In recent years, several in vitro studies and murine models
      have focused on the elucidation of these modifications. Furthermore,
      investigations of the human population have correlated Toxoplasma seropositivity
      with changes in neurological functions; however, the complex underlying
      mechanisms of the subtle behavioural alteration are still not fully understood.
      The parasites are able to induce direct modifications in the infected cells, for
      example by altering dopamine metabolism, by functionally silencing neurons as
      well as by hindering apoptosis. Moreover, indirect effects of the peripheral
      immune system and alterations of the immune status of the CNS, observed during
      chronic infection, might also contribute to changes in neuronal connectivity and
      synaptic plasticity. In this review, we will provide an overview and highlight
      recent advances, which describe changes in the neuronal function and morphology
      upon T. gondii infection.

PMID- 25376391
TI  - Water-Soluble Molecularly Imprinted Nanoparticles (MINPs) with Tailored,
      Functionalized, Modifiable Binding Pockets.
AB  - Construction of receptors with binding sites of specific size, shape, and
      functional groups is important to both chemistry and biology. Covalent imprinting
      of a photocleavable template within surface-core doubly cross-linked micelles
      yielded carboxylic acid-containing hydrophobic pockets within the water-soluble
      molecularly imprinted nanoparticles. The functionalized binding pockets were
      characterized by their binding of amine- and acid-functionalized guests under
      different pH values. The nanoparticles, on average, contained one binding site
      per particle and displayed highly selective binding among structural analogues.
      The binding sites could be modified further by covalent chemistry to modulate
      their binding properties.

PMID- 25376392
TI  - Application of a nanostructured supramolecular solvent for the microextraction of
      diphenylamine and its mono-nitrated derivatives from unburned single-base
      propellants.
AB  - A supramolecular solvent made up of nano-sized inverted hexagonal aggregates of 1
      octanol is proposed for the microextraction of diphenylamine and its mono
      nitrated derivatives in unburned single-base propellants. The procedure included
      the extraction of sub-gram quantities (30 mg) of homogenized propellant with 1.5
      mL of the supramolecular solvent. Several conditions affecting extraction
      efficiency, for example the concentrations of the major components of the
      supramolecular solvent (tetrahydrofuran and alkanol), alkanol type, solvent pH,
      and extraction time, were investigated and optimized. The main forces for the
      microextraction of analytes in the nanostructured supramolecular solvent include
      both dispersion and hydrogen bond interactions. This mixed-mode mechanism
      resulted in high extraction efficiencies reaching low method detection limits
      (0.005-0.012 mg/g) without the need for extract evaporation. Under the optimum
      conditions, recoveries in samples ranged between about 82.6 and 98.7%. Compared
      to the reference method, the proposed method is simple and rapid, delivering
      accurate and precise results, and can be applied for routine determination of
      diphenylamine and its derivatives in propellants. The precision of the method,
      expressed as relative standard deviation, was about 4.3-10.9%. 

PMID- 25376393
TI  - Synthesis and characterization of 2-pyridylsulfur pentafluorides.
AB  - Current approaches to prepare SF5 -substituted heterocycles during the synthesis
      of targeted heterocyclic compounds require the use of SF5 -functionalized aryl or
      alkyne reagents or SF5 Cl as a source of the SF5  functional group. Herein we
      report that excess oxidative fluorination of 2,2'-dipyridyl disulfide with a
      KF/Cl2 /MeCN system leads to the formation of thirteen new 2-pyridylsulfur
      chlorotetrafluorides (2-SF4 Cl-pyridines). These molecules are found to undergo
      further chlorine-fluorine exchange reactions by treatment with silver(I) fluoride
      enabling ready access to a series of ten new substituted 2-pyridylsulfur
      pentafluorides (2-SF5 -pyridines). This is the first preparatively simple and
      readily scalable example of the transformation of an existing heterocyclic sulfur
      functionality to prepare SF5 -substituted heterocycles. 

PMID- 25376394
TI  - Preventing weight gain with calorie-labeling.
AB  - OBJECTIVE: Calorie-labeling has been suggested as an anti-obesity measure but
      there is no evidence for its effect, to date. Early adulthood is a critical life
      cycle period for unwanted weight gain and obesity development. This study
      examined whether providing calorie information would help young adults to avoid
      weight gain. METHODS: Using a pragmatic interrupted time-series study design,
      weight changes over 36 weeks were reported among two year-groups, each of 120
      young adults, similar in age, gender, and ethnicity, living in fully-catered
      accommodation. Year 1: subjects were observed without calorie-labeling, apart
      from a 5-week pilot. Year 2: calorie-labeling was present prominently and
      consistently at main meals for 30 of the 36 weeks. RESULTS: Mean weight changes
      over 36 weeks, per protocol, were +3.5 kg (95% CI = 2.8-4.1 kg) (n = 64) in Year
      1 and -0.15 kg (95% CI = -0.7-0.3 kg) (n = 87) in Year 2. Weight changes were
      significantly different between years, for males and females (both P < 0.001).
      Intention-to-treat analysis showed similar results. Relative Risk for weight gain
      in Year 2, compared to Year 1, was 0.5 (P < 0.0001). CONCLUSIONS: Calorie
      labeling was associated with a 3.5 kg less weight gain, representing a low-cost
      "nudging" approach to combat the rapid weight gain seen in young adults.

PMID- 25376395
TI  - Objective physical activity and weight loss in adults: the step-up randomized
      clinical trial.
AB  - OBJECTIVE: To examine the amount of objectively measured MVPA and LPA that is
      associated with long-term weight loss and the maintenance of clinically
      significant weight loss. METHODS: Adults (N = 260; BMI: 25 to <40 kg/m(2) ; age:
      18-55 years) participated in an 18-month behavioral weight loss intervention and
      were prescribed a low-calorie diet and increased physical activity. Change in
      weight and objectively measured physical activity were assessed. MVPA > 10 (MET
      min/week) was computed from bouts >10 min and >3.0 METs and MVPA < 10 was
      computed from bouts <10 min in duration and >3.0 METs. LPA was computed from
      bouts between 1.5 to <3.0 METs. RESULTS: When grouped on percent weight loss at
      18 months, there was a significant group * time interaction effect (P < 0.0001)
      for both MVPA > 10 and LPA, with both measures being significantly greater at 18
      months in those with >10% weight loss. Similar results were observed for MVPA >
      10 and LPA with participants grouped on achieving >10% weight loss at 6 months
      and sustaining this at 18 months. CONCLUSIONS: MVPA > 10 of 200-300 min per week,
      coupled with increased amounts of LPA, are associated with improved long-term
      weight loss. Interventions should promote engagement in these amounts and types
      of physical activity.

PMID- 25376396
TI  - Comparative effectiveness of three doses of weight-loss counseling: two-year
      findings from the rural LITE trial.
AB  - OBJECTIVE: To evaluate the effects and costs of three doses of behavioral weight
      loss treatment delivered via Cooperative Extension Offices in rural communities.
      METHODS: Obese adults (N = 612) were randomly assigned to low, moderate, or high
      doses of behavioral treatment (i.e., 16, 32, or 48 sessions over two years) or to
      a control condition that received nutrition education without instruction in
      behavior modification strategies. RESULTS: Two-year mean reductions in initial
      body weight were 2.9% (95% Credible Interval = 1.7-4.3), 3.5% (2.0-4.8), 6.7%
      (5.3-7.9), and 6.8% (5.5-8.1) for the control, low-, moderate-, and high-dose
      conditions, respectively. The moderate-dose treatment produced weight losses
      similar to the high-dose condition and significantly larger than the low-dose and
      control conditions (posterior probability > 0.996). The percentages of
      participants who achieved weight reductions >= 5% at two years were significantly
      higher in the moderate-dose (58%) and high-dose (58%) conditions compared with
      low-dose (43%) and control (40%) conditions (posterior probability > 0.996). Cost
      effectiveness analyses favored the moderate-dose treatment over all other
      conditions. CONCLUSIONS: A moderate dose of behavioral treatment produced two
      year weight reductions comparable to high-dose treatment but at a lower cost.
      These findings have important policy implications for the dissemination of weight
      loss interventions into communities with limited resources.

PMID- 25376397
TI  - The role of small heterodimer partner in nonalcoholic fatty liver disease
      improvement after sleeve gastrectomy in mice.
AB  - OBJECTIVE: Bile acids (BA) are elevated after vertical sleeve gastrectomy (VSG)
      and farnesoid-X-receptor (FXR) is critical to the success of murine VSG. BA
      downregulate hepatic lipogenesis by activating the FXR-small heterodimer partner
      (SHP) pathway. The role of SHP in fatty liver disease improvement after VSG was
      tested. METHODS: Wild type (WT), SHP liver transgenic (SHP-Tg), and SHP knockout
      (SHP-KO) high-fat diet (HFD) fed mice underwent either VSG or Sham surgery. Body
      weight, BA level and composition, steatosis, and BA metabolism gene expression
      were evaluated. RESULTS: Obese WT mice post-VSG lost weight, reduced steatosis,
      decreased plasma alanine aminotransferase (ALT), had more BA absorptive ileal
      area, and elevated serum BA. Obese SHP-Tg mice post-VSG also lost weight and had
      decreased steatosis. SHP-KO mice were however resistant to steatosis despite
      weight gain on a HFD. Further SHP-KO mice that underwent VSG lost weight, but
      developed hepatic inflammation and had increased ALT. CONCLUSIONS: VSG produces
      weight loss independent of SHP status. SHP ablation creates a proinflammatory
      phenotype which is exacerbated after VSG despite weight loss. These inflammatory
      alterations are possibly related to factors extrinsic to a direct manifestation
      of NASH.

PMID- 25376398
TI  - Cognitive performance and BMI in childhood: Shared genetic influences between
      reaction time but not response inhibition.
AB  - OBJECTIVE: The aim of this work is to understand whether shared genetic
      influences can explain the association between obesity and cognitive performance,
      including slower and more variable reaction times (RTs) and worse response
      inhibition. METHODS: RT on a four-choice RT task and the go/no-go task, and
      commission errors on the go/no-go task for 1,312 twins ages 7-10 years were
      measured. BMI was measured at 9-12 years. Biometric twin models were run to give
      an estimate of the genetic correlation (rG ) between body mass index (BMI) and
      three cognitive measures: mean RT (MRT), RT variability (RTV; the standard
      deviation of RTs), and commission errors (a measure of response inhibition).
      RESULTS: Genetic correlations indicated that 20%-30% of the genes underlying BMI
      were shared with both RT measures. However, only small phenotypic correlations
      between MRT and RTV with later BMI (rPh  = ~0.1) were observed. Commission errors
      were unassociated with later BMI (rPh  = -0.03, ns). CONCLUSIONS: Our results are
      the first to demonstrate significant shared genetic effects between RT
      performance and BMI. Our findings add biological support to the notion that
      obesity is associated with slower and more variable RTs. However, our results
      also emphasize the small nature of the association, which may explain previous
      negative findings.

PMID- 25376400
TI  - Interface atomic-scale structure and its impact on quantum electron transport.
AB  - Local structure, chemistry, and bonding at interfaces often radically affect the
      properties of materials. A combination of scanning transmission electron
      microscopy and density functional theory calculations reveals an atomic layer of
      carbon at a SiC/Ti3 SiC2 interface in Ohmic contact to p-type SiC, which results
      in stronger adhesion, a lowered Schottky barrier, and enhanced transport. This is
      a key factor to understanding the origin of the Ohmic nature. 

PMID- 25376399
TI  - Kidney function in severely obese adolescents undergoing bariatric surgery.
AB  - OBJECTIVE: Determine objective measures of kidney function and analyze factors
      associated with kidney dysfunction in severely obese adolescents undergoing
      weight loss surgery were described. METHODS: Cross-sectional data from 242
      adolescent participants in the Teen-Longitudinal Assessment of Bariatric Surgery
      (Teen-LABS) study before weight loss surgery were analyzed. Kidney status was
      assessed by measuring urine albumin creatinine ratio to determine
      microalbuminuria and by calculating serum cystatin C-based estimated glomerular
      filtration rate (eGFR) to assess kidney function. RESULTS: Mean age and median
      body mass index (BMI) were 17.1 years and 50.5 kg/m(2) , respectively; 76% were
      females and 65% were non-Hispanic white race. Fourteen percent of the cohort had
      microalbuminuria, and 3% had macroalbuminuria; 3% had eGFR < 60 ml/min/1.73 m(2)
      , and 7.1% had eGFR > 150 ml/min/1.73 m(2) . In adjusted analyses, female gender
      and increasing ferritin levels were significantly associated with the presence of
      microalbuminuria/macroalbuminuria. Increasing BMI and homeostasis model
      assessment of insulin resistance values were significantly associated with lower
      eGFR. CONCLUSIONS: A significant number of severely obese adolescents undergoing
      weight loss surgery have evidence of early kidney dysfunction. Longitudinal
      studies following weight loss surgery in these individuals are needed to
      determine whether these kidney abnormalities are reversible following weight loss
      therapy.

PMID- 25376401
TI  - Pediatric tracheal tumor masked by a history of travel: case report and
      literature review.
AB  - A previously healthy 10-year-old female reported a 1-month history of wheezing
      and hemoptysis. Initial evaluation and treatment were focused on refractory
      reactive airway disease and infectious etiologies prompted by her recent travels
      in Africa. Worsening respiratory distress prompted emergent evaluation with
      imaging and endoscopy. Bronchoscopy diagnosed a distal tracheal tumor; pathology
      of this tumor was benign fibrous histiocytoma. Successful management of this
      condition included imaging, rigid bronchoscopy with biopsy, and tracheal
      resection to surgically excise the lesion. Although rare, tracheal tumors should
      be considered when presentation of asthma is atypical and nonresponsive to
      medical interventions.

PMID- 25376403
TI  - Reduced neonatal regulatory T cell response to microbial stimuli associates with
      subsequent eczema in high-risk infants.
AB  - BACKGROUND: Regulatory T cells (Treg) play an essential role in early immune
      programming and shaping the immune response towards a pro-allergic or tolerant
      state. We evaluated cord blood Treg and cytokine responses to microbial and non
      microbial stimuli in infants at high risk of allergic disease and their
      associations with development of allergic disease in the first year. METHODS:
      Cord blood mononuclear cells from 72 neonates were cultured with toll-like
      receptors (TLR2) ligands: lipoteichoic acid (LTA) and heat-killed Lactobacillus
      rhamnosus GG (HKL); TLR4 ligand: lipopolysaccharide (LPS); ovalbumin (OVA); anti
      CD3; or media for 48 h. Treg numbers and Treg cytokines were assessed in relation
      to allergic disease outcomes during the first year of life (eczema and atopic
      sensitization). RESULTS: Infants with eczema (n = 24) had reduced percentages of
      FoxP3(hi)CD25(hi) Treg in LTA (p = 0.01, adj p = 0.005) and HKL (p = 0.04, adj p
      = 0.02) stimulated cultures as well as reduced IL-10 (p = 0.01) production
      following HKL stimulation compared to those without eczema (n = 48). No
      differences in Treg or cytokine responses to LPS, OVA or anti-CD3 were seen.
      Infants who developed sensitization had lower percentages of Treg following TLR2
      stimulation (but not other stimuli) compared to non-sensitized infants.
      CONCLUSIONS: High-risk children who develop allergic disease in the first year of
      life have deficient Treg responses to microbial stimuli but not allergen from the
      time of birth, which may contribute to failure of immune tolerance development in
      infancy.

PMID- 25376402
TI  - Fate and effects of clothianidin in fields using conservation practices.
AB  - Despite the extensive use of the neonicotinoid insecticide clothianidin, and its
      known toxicity to beneficial insects such as pollinators, little attention has
      been given to its fate under agricultural field conditions. The present study
      investigated the fate and toxicity of clothianidin applied every other year as a
      corn seed-coating at 2 different rates, 0.25 mg/seed and 0.50 mg/seed, in an
      agricultural field undergoing a corn-soybean annual rotation, and conservation
      tillage. Concentrations were measured in soil, surface runoff, infiltration, and
      groundwater from 2011 to 2013. Clothianidin was detected at low concentrations in
      soil and water throughout the 2-yr corn and soybean rotation. Low and no-tillage
      had little or no effect on clothianidin concentrations. Laboratory toxicity
      bioassays were performed on nontarget species, including Daphnia magna, Hyalella
      azteca, Chironomus dilutus, Pimephales promelas and Eisenia fetida. Risk
      quotients were calculated from clothianidin concentrations measured in the field
      and compared with the laboratory toxicity bioassay results to assess the
      environmental risk of the insecticide. The risk quotient was found to be lower
      than the level of concern for C. dilutus, which was the most sensitive species
      tested; therefore, no short-term environmental risk was expected for the species
      investigated in the present study.

PMID- 25376404
TI  - Semen quality and the level of reproductive hormones after environmental exposure
      to pyrethroids.
AB  - OBJECTIVES: The aim of this study was to determine whether the environmental
      exposure to pyrethroids affects semen quality and the level of reproductive
      hormones in men. METHODS: The study population consisted of 334 men who attended
      the infertility clinic for diagnostic purposes and who had normal semen
      concentration of 15 to 300 mln/mL. Participants were interviewed and provided a
      semen sample. The pyrethroids metabolites-3-phenoxybenzoic acid (3PBA), cis-3
      (2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), trans-3
      (2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA), and cis-2,2
      dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) were analyzed in
      the urine using a validated gas chromatography ion-trap mass spectrometry method.
      RESULTS: Urinary pyrethroids metabolites levels were significantly associated
      with an increase in the percentage of sperm with abnormal morphology and decrease
      in sperm concentration, the level of testosterone, and computer-aided semen
      analysis parameters. CONCLUSIONS: Environmental pyrethroids exposure may affect
      semen quality and the level of reproductive hormones.

PMID- 25376405
TI  - State-level estimates of obesity-attributable costs of absenteeism.
AB  - OBJECTIVE: To provide state-level estimates of obesity-attributable costs of
      absenteeism among working adults in the United States. METHODS: Nationally
      representative data from the National Health and Nutrition Examination Survey for
      1998 to 2008 and from the Behavioral Risk Factor Surveillance System for 2012 are
      examined. The outcome is obesity-attributable workdays missed in the previous
      year because of health and their costs to states. RESULTS: Obesity, but not
      overweight, is associated with a significant increase in workdays absent, from
      1.1 to 1.7 extra days missed annually compared with normal-weight employees.
      Obesity-attributable absenteeism among American workers costs the nation an
      estimated $8.65 billion per year. CONCLUSIONS: Obesity imposes a considerable
      financial burden on states, accounting for 6.5% to 12.6% of total absenteeism
      costs in the workplace. State legislatures and employers should seek effective
      ways to reduce these costs.

PMID- 25376406
TI  - Inducing a health-promoting change process within an organization: the
      effectiveness of a large-scale intervention on social capital, openness, and
      autonomous motivation toward health.
AB  - OBJECTIVE: To examine the effectiveness of an organizational large-scale
      intervention applied to induce a health-promoting organizational change process.
      DESIGN AND METHODS: A quasi-experimental, "as-treated" design was used.
      Regression analyses on data of employees of a Dutch dairy company (n = 324) were
      used to examine the effects on bonding social capital, openness, and autonomous
      motivation toward health and on employees' lifestyle, health, vitality, and
      sustainable employability. Also, the sensitivity of the intervention components
      was examined. RESULTS: Intervention effects were found for bonding social
      capital, openness toward health, smoking, healthy eating, and sustainable
      employability. The effects were primarily attributable to the intervention's
      dialogue component. CONCLUSIONS: The change process initiated by the large-scale
      intervention contributed to a social climate in the workplace that promoted
      health and ownership toward health. The study confirms the relevance of
      collective change processes for health promotion.

PMID- 25376407
TI  - Making the workplace a more effective site for prevention of noncommunicable
      diseases in adults.
AB  - OBJECTIVE: Efforts to realize the potential of disease prevention in the United
      States have fallen behind those of peer countries, and workplace disease
      prevention is a major gap. This article investigates the reasons for this gap.
      METHODS: Literature review and expert discussions. RESULTS: Obstacles to
      effective use of workplace disease prevention include limited leadership and
      advocacy, poor alignment of financial incentives, limitations in research quality
      and investment, regulation that does not support evidence-based practice, and a
      dearth of community-employer partnerships. CONCLUSIONS: We make recommendations
      to address these obstacles, such as the inclusion of health metrics in corporate
      reporting, making the workplace a central component of the strategy to combat the
      effect of noncommunicable diseases, and linking prevention directly benefit
      businesses' bottom lines.

PMID- 25376408
TI  - Transition of occupational health issues associated with stabilization and
      decommissioning of the nuclear reactors in the Fukushima Daiichi Nuclear Power
      Plant through 2013.
AB  - OBJECTIVE: To clarify the occupational health (OH) issues that arose, what
      actions were taken, and the OH performances during the disaster involving the
      Fukushima Daiichi Nuclear Power Plant and thus improve the OH management system
      with respect to long-term decommissioning work and preparation for future
      disasters. METHODS: We used information in advisory reports to the Tokyo Electric
      Power Company by an OH expert group, observation through support activities, and
      data officially released by the Tokyo Electric Power Company. RESULTS:
      Occupational health issues transitioned as work progressed and seasons changed.
      They were categorized into OH management system establishment, radiation exposure
      control, heat illness prevention, infectious disease prevention and control, and
      fitness for workers' duties. CONCLUSIONS: Occupational health management systems
      involving OH experts should be implemented to manage multiple health risks with
      several conflicts and trade-offs after a disaster.

PMID- 25376410
TI  - Assessing the risk of work-related international travel.
AB  - OBJECTIVE: To identify factors affecting the likelihood of requiring medical
      services during international business trips. METHODS: Data from more than
      800,000 international trips and medical assistance cases provided to 48
      multinational corporations in 2009. Travel destination countries were grouped
      into four a priori risk-related categories. RESULTS: Travel to "low" medical risk
      countries in aggregate accounted for more hospitalizations and medical
      evacuations than travel to "high" medical risk countries. Nevertheless, the risk
      per trip was much higher for travel to higher medical risk countries.
      CONCLUSIONS: Corporations with employees on international travel should allocate
      sufficient resources to manage and ideally prevent medical issues during business
      travel. Travel medicine must focus on more than infectious diseases, and programs
      are necessary for both high- and low-risk regions. Improved understanding of
      travel-related needs determines resource allocation and risk mitigation efforts.

PMID- 25376409
TI  - Associations of work hours, job strain, and occupation with endothelial function:
      the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - OBJECTIVE: To investigate associations of work hours, job control, job demands,
      job strain, and occupational category with brachial artery flow-mediated dilation
      (FMD) in 1499 Multi-Ethnic Study of Atherosclerosis participants. METHODS: Flow
      mediated dilation was obtained using high-resolution ultrasound. Mean values of
      FMD were examined across categories of occupation, work hours, and the other
      exposures using regression analyses. RESULTS: Occupational category was
      significantly associated with FMD overall, with blue-collar workers showing the
      lowest mean values-management/professional = 4.97 +/- 0.22%; sales/office = 5.19
      +/- 0.28%; services = 4.73 +/- 0.29%; and blue-collar workers = 4.01 +/- 0.26%
      (adjusted P < 0.001). There was evidence of effect modification by sex
      (interaction P = 0.031)-significant associations were observed among women
      (adjusted P = 0.002) and nearly significant results among men (adjusted P =
      0.087). Other exposures were not significantly associated with FMD. CONCLUSIONS:
      Differences in endothelial function may account for some of the variation in
      cardiovascular disease across occupational groups.

PMID- 25376411
TI  - Assessing risk and improving travel vaccine programs for business travelers.

PMID- 25376412
TI  - General mortality patterns in appalachian coal-mining and non-coal-mining
      counties.
AB  - OBJECTIVE: To determine whether mortality disparities in Appalachia are due to
      coal mining or other factors. METHODS: Unadjusted and covariate adjusted rate
      ratio models calculated total, all external, and all cancer mortality rates from
      1960 to 2009 for cumulative total, surface, and underground coal production in
      coal-mining counties compared with non-coal-mining counties. RESULTS: No coal
      related statistically significant elevations in total or all external mortality
      were found. Control for covariates attenuated rate ratios for all levels of coal
      mining. All forms of coal were statistically significant in the adjusted rate
      ratio models for all cancer mortality, with 4% to 6% excesses in the highest
      quartiles of production. CONCLUSIONS: Total and all external mortalities do not
      seem to be related to coal production in Appalachia, but all cancer mortality
      should be further examined. Additional causes of death should also be considered.

PMID- 25376413
TI  - The association of respiratory hospitalization rates in WV counties, total,
      underground, and surface coal production and sociodemographic covariates.
AB  - BACKGROUND: Exposures associated with coal mining have long been linked to
      occupational disease. More recently, investigators have suggested that this
      industry may affect community health. METHODS: We explored associations between
      age-adjusted, county-level respiratory disease hospitalization rates (RHRs) in
      West Virginia and total, surface, and underground coal production, taking into
      account relevant sociodemographic and behavioral covariates. RHRs were calculated
      for 2005 to 2009, and analyses were performed to assess the effect of coal
      production after adjusting for sociodemographic factors. RESULTS: After
      controlling for percent below poverty, percent urban, and smoking, neither total
      nor underground tonnage was associated with RHR. Surface coal production,
      however, was significantly related with RHR (P < 0.05). CONCLUSIONS: Surface coal
      production makes a small but significant contribution to RHR in West Virginia
      after accounting for other important sociodemographic and behavioral determinants
      of health.

PMID- 25376416
TI  - Surveillance for angiosarcoma of the liver among vinyl chloride workers.
AB  - OBJECTIVE: We report the results of our angiosarcoma of the liver (ASL) registry
      to assess the occurrence, the impact of exposures to vinyl chloride, and to
      quantify latency. METHODS: We examined more than 73,000 death certificates of
      North American workers employed between 1940 and 2008. RESULTS: We found 13
      deaths of ASL among workers with vinyl chloride exposure. All 13 occurred at
      single plant among workers with high vinyl chloride exposure. The mean latency
      after first exposure was 36.5 years ranging from 24 to 56 years. No ASL deaths
      occurred among workers with vinyl chloride exposures after 1974, when exposures
      were reduced. CONCLUSIONS: We may have seen the last case of ASL among workers
      exposed to vinyl chloride. Nevertheless, given the long latency of this cancer,
      continued surveillance seems prudent.

PMID- 25376414
TI  - The effect of an e-health intervention designed to reduce prolonged occupational
      sitting on mean arterial pressure.
AB  - OBJECTIVE: To evaluate the effect of a workplace health intervention designed to
      reduce prolonged occupational sitting on the mean arterial pressure (MAP) of desk
      based employees. METHODS: This randomized controlled trial involved an
      experimental group who received an e-health intervention and a control group who
      did not. The 13-week intervention passively prompted participants to stand and
      engage in short bouts of office-based physical activity by interrupting prolonged
      occupational sitting time periodically throughout the workday. Mean arterial
      pressure was measured at pretest and posttest. RESULTS: Between pretest and
      posttest the experimental group significantly reduced their MAP, whereas MAP in
      the control group did not. CONCLUSIONS: A workplace e-health intervention
      designed to reduce prolonged occupational sitting was effective in decreasing MAP
      in desk-based employees.

PMID- 25376415
TI  - The implementation of multiple lifestyle interventions in two organizations: a
      process evaluation.
AB  - OBJECTIVE: To evaluate the implementation of a multicomponent lifestyle
      intervention at two different worksites. METHODS: Data on eight process
      components were collected by means of questionnaires and interviews. Data on the
      effectiveness were collected using questionnaires. RESULTS: The program was
      implemented partly as planned, and 84.0% (max 25) and 85.7% (max 14) of all
      planned interventions were delivered at the university and hospital,
      respectively. Employees showed high reach (96.6%) and overall participation
      (75.1%) but moderate overall satisfaction rates (6.8 +/- 1.1). Significant
      intervention effects were found for days of fruit consumption (beta = 0.44
      days/week, 95% CI: 0.02 to 0.85) in favor of the intervention group. CONCLUSIONS:
      The study showed successful reach, dose, and maintenance but moderate fidelity
      and satisfaction. Mainly relatively simple and easily implemented interventions
      were chosen, which were effective only in improving employees' days of fruit
      consumption.

PMID- 25376417
TI  - Process evaluation of a multifaceted health program aiming to improve physical
      activity levels and dietary patterns among construction workers.
AB  - OBJECTIVE: To evaluate the process of a health promotion program, aiming to
      improve physical activity levels and diet among construction workers. METHODS:
      The process evaluation was conducted after the RE-AIM framework for the
      evaluation of the public health impact of health promotion interventions.
      Effectiveness was assessed on motivational stage-of-change, self-efficacy, and
      decisional balance for physical activity and dietary behavior. RESULTS: The
      external validity of the trial was satisfactory with representative reach of
      workers and adoption of workplace units in the participating construction
      company. The extent to which the program was implemented as intended was modest.
      The intervention was effective on participants' progress through stages of
      behavior change. CONCLUSIONS: Based on the RE-AIM dimensions, it is concluded
      that for construction workers, the program is feasible and potentially effective,
      but adjustments are required before widespread implementation.

PMID- 25376420
TI  - Wind turbines and health: a critical review of the scientific literature.
AB  - OBJECTIVE: This review examines the literature related to health effects of wind
      turbines. METHODS: We reviewed literature related to sound measurements near
      turbines, epidemiological and experimental studies, and factors associated with
      annoyance. RESULTS: (1) Infrasound sound near wind turbines does not exceed
      audibility thresholds. (2) Epidemiological studies have shown associations
      between living near wind turbines and annoyance. (3) Infrasound and low-frequency
      sound do not present unique health risks. (4) Annoyance seems more strongly
      related to individual characteristics than noise from turbines. DISCUSSION:
      Further areas of inquiry include enhanced noise characterization, analysis of
      predicted noise values contrasted with measured levels postinstallation,
      longitudinal assessments of health pre- and postinstallation, experimental
      studies in which subjects are "blinded" to the presence or absence of infrasound,
      and enhanced measurement techniques to evaluate annoyance.

PMID- 25376421
TI  - Do symptoms and physical examination findings predict elbow pain and functional
      outcomes in a working population?

PMID- 25376422
TI  - Opioids and safety-sensitive work.

PMID- 25376423
TI  - Opioids and safety-sensitive work.

PMID- 25376424
TI  - The value of prospective case reports in occupational respiratory allergy.

PMID- 25376425
TI  - Combining [arene-Ru] with azocarboxamide to generate a complex with cytotoxic
      properties.
AB  - Azocarboxamide (azcH) has been combined for the first time with [Ru-Cym] to
      generate metal complexes with N,N- and N,O-coordination mode, [(Cym)Ru(azc)Cl]
      and [(Cym)Ru(azcH)Cl](+) [PF6 ](-). Geometric and electronic structures of the
      complexes are reported along with their in vitro activities against different
      tumour cell lines and preliminary results on solution chemistry. Compound
      [(Cym)Ru(azc)Cl] exhibited remarkable cytotoxic properties. It was cell-type
      specific and had comparable IC50 values towards both cancer cells and their drug
      resistant subline. A tenfold increase in the sensitivity towards [(Cym)Ru(azc)Cl]
      was noted for the tumour cells with depleted intracellular glutathione (GSH)
      level, suggesting the essential role of GSH in cell response to this compound.

PMID- 25376426
TI  - Quantification of an antitumor agent (copen) in rat plasma by liquid
      chromatography-electrospray ionization tandem mass spectrometry and its
      application in a preclinical pharmacokinetic study.
AB  - Copen is a derivative obtained from the structural modification of osthole, which
      inhibits tumoral proliferation in many tumor cell lines. A rapid and sensitive
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established
      for the quantification of copen in rat plasma. After a simple sample preparation
      procedure by one-step protein precipitation with methanol, copen and bicalutamide
      (internal standard, IS) were chromatographed on a Zorbax SB-C18 (4.6*100 mm, 1.8
      um) column with a mobile phase consisting of methanol-5 mm ammonium formate water
      with 0.1% formic acid (80:20, v/v). MS detection was performed on a triple
      quadrupole tandem mass spectrometer in the multiple reaction monitoring mode with
      a positive eletrospray ionization source. The assay was validated in the
      concentration range of 51.58-20,630 ng/mL, with a limit of quantitation (LOQ) of
      51.58 ng/mL. The intra- and inter-day precisions (relative standard deviation)
      were <=3.21 and <=11.3%, respectively, with accuracy (%) in the range of 94.66
      102.1%. The method was fully validated in a study of the pharmacokinetics of
      copen (25 mg/kg) after intragastric administration in rats.

PMID- 25376428
TI  - Bilayer molecular assembly at a solid/liquid interface as triggered by a mild
      electric field.
AB  - The construction of a spatially defined assembly of molecular building blocks,
      especially in the vertical direction, presents a great challenge for surface
      molecular engineering. Herein, we demonstrate that an electric field applied
      between an STM tip and a substrate triggered the formation of a bilayer structure
      at the solid-liquid interface. In contrast to the typical high electric-field
      strength (10(9)  V m(-1) ) used to induce structural transitions in
      supramolecular assemblies, a mild electric field (10(5)  V m(-1) ) triggered the
      formation of a bilayer structure of a polar molecule on top of a nanoporous
      network of trimesic acid on graphite. The bilayer structure was transformed into
      a monolayer kagome structure by changing the polarity of the electric field. This
      tailored formation and large-scale phase transformation of a molecular assembly
      in the perpendicular dimension by a mild electric field opens perspectives for
      the manipulation of surface molecular nanoarchitectures. 

PMID- 25376427
TI  - Bringing PROMIS to practice: brief and precise symptom screening in ambulatory
      cancer care.
AB  - BACKGROUND: Supportive oncology practice can be enhanced by the integration of a
      brief and validated electronic patient-reported outcome assessment into the
      electronic health record (EHR) and clinical workflow. METHODS: Six hundred thirty
      six women receiving gynecologic oncology outpatient care received instructions to
      complete clinical assessments through Epic MyChart, an EHR patient communication
      portal. Patient Reported Outcomes Measurement Information System (PROMIS)
      computer adaptive tests (CATs) were administered to assess fatigue, pain
      interference, physical function, depression, and anxiety. Checklists identified
      psychosocial concerns, informational and nutritional needs, and risk factors for
      inadequate nutrition. Assessment results, including PROMIS T scores with
      documented severity thresholds, were immediately populated in the EHR. Clinicians
      were notified of clinically elevated symptoms through EHR messages. EHR
      integration was designed to provide automated triage to social work providers for
      psychosocial concerns, to health educators for information, and to dietitians for
      nutrition-related concerns. RESULTS: Four thousand forty-two MyChart messages
      sent, and 3203 (79%) were reviewed by patients. The assessment was started by
      1493 patients (37%), and once they started, 93% (1386 patients) completed the
      assessment. According to first assessments only, 49.8% of the patients who
      reviewed the MyChart message completed the assessment. Mean PROMIS CAT T scores
      indicated a lower level of physical function and elevated anxiety in comparison
      with the general population. Fatigue, pain, and depression scores were comparable
      to those of the general population. Impaired physical functioning was the most
      common basis for clinical alerts and occurred in 4% of the patients. CONCLUSIONS:
      PROMIS CATs were used to measure common cancer symptoms in routine oncology
      outpatient care. Immediate EHR integration facilitated the use of symptom
      reporting as the basis for referral to psychosocial and supportive care.

PMID- 25376429
TI  - Sex differences in cognitive regulation of psychosocial achievement stress: brain
      and behavior.
AB  - Although cognitive regulation of emotion has been extensively examined, there is
      a lack of studies assessing cognitive regulation in stressful achievement
      situations. This study used functional magnetic resonance imaging in 23 females
      and 20 males to investigate cognitive downregulation of negative, stressful
      sensations during a frequently used psychosocial stress task. Additionally,
      subjective responses, cognitive regulation strategies, salivary cortisol, and
      skin conductance response were assessed. Subjective response supported the
      experimental manipulation by showing higher anger and negative affect ratings
      after stress regulation than after the mere exposure to stress. On a neural
      level, right middle frontal gyrus (MFG) and right superior temporal gyrus (STG)
      were more strongly activated during regulation than nonregulation, whereas the
      hippocampus was less activated during regulation. Sex differences were evident:
      after regulation females expressed higher subjective stress ratings than males,
      and these ratings were associated with right hippocampal activation. In the
      nonregulation block, females showed greater activation of the left amygdala and
      the right STG during stress than males while males recruited the putamen more
      robustly in this condition. Thus, cognitive regulation of stressful achievement
      situations seems to induce additional stress, to recruit regions implicated in
      attention integration and working memory and to deactivate memory retrieval.
      Stress itself is associated with greater activation of limbic as well as
      attention areas in females than males. Additionally, activation of the memory
      system during cognitive regulation of stress is associated with greater perceived
      stress in females. Sex differences in cognitive regulation strategies merit
      further investigation that can guide sex sensitive interventions for stress
      associated disorders.

PMID- 25376430
TI  - Metal-catalyzed cascade reactions: useful synthetic tools for the preparation of
      polycyclic arenes.
AB  - This account summarizes our recent efforts to synthesize numerous important and
      interesting polycyclic arenes under mild conditions using metal-catalyzed
      protocols. The palladium-catalyzed annulations of 2-iodobiphenyls or 2,2'
      diiodobiphenyls with alkynes efficiently generated phenanthrene derivatives. This
      synthetic method was utilized as the key step when preparing phenanthrene-based
      alkaloids, tetrabenzopyracylenes and persubstituted [8]circulenes. Depending on
      whether a palladium or nickel catalytic system was used, 1-ethynyl-8
      iodonaphthalenes underwent either a cyclodimerization or a nitrile-incorporated
      cascade reaction to produce zethrenes or pyrroloarenes, respectively. Methylene
      bridged polyarenes are generated easily from 2-halo-2'-methylbiaryls through
      benzylic C-H bond activation and subsequent carbon-carbon bond formation, and
      palladium complexes promote the arylation of methylene carbons. The palladium
      catalyzed annulations of 1,8-bis(arylethynyl)naphthalene derivatives with o
      diiodoarenes yielded benzo[k]fluoranthene-based linear acenes, which can be
      applied to synthesize highly curved fragments of fullerenes. The self-reactions
      of diarylethynes formed either dihydrocyclopenta[a]indenes or octaaryl-1,3,5,7
      octatetraenes through palladium-catalyzed cycloisomerization or nickel-catalyzed
      tetramerization, respectively. In the presence of palladium catalysts, the
      hydroalkynylation of terminal arylalkynes directly generated angular
      trimerization adduct dienynes. 

PMID- 25376431
TI  - A randomised, single-blind technical study comparing the ultrasonic visibility of
      smooth-surfaced and textured needles in a soft embalmed cadaver model.
AB  - Visibility of the needle tip and shaft is important during ultrasound-guided
      regional anaesthesia in order to prevent nerve trauma. Tip and shaft visibility
      is reduced when needles are inserted in-plane at wide angles and out-of-plane at
      narrow angles to the ultrasound probe. Although textured needles are more
      reflective than smooth needles, we hypothesised that poor visibility of the tip
      and shaft still remained using the above angle-probe combinations. In a single
      blind study, we compared the visibility of a textured Tuohy needle, a textured
      single-shot needle and a conventional smooth-surfaced Tuohy needle when inserted
      into the biceps and deltoid muscles of a soft embalmed cadaver. One hundred and
      forty-four needles were block-randomised to in-plane and out-of-plane insertions
      at 30 degrees , 45 degrees , 60 degrees  and 75 degrees  to the ultrasound beam.
      Two blinded raters assessed needle tip visibility on video recordings of the
      insertions using a binary scale (0 = not visible, 1 = visible) and shaft
      visibility using a 5-point Likert scale. The median (IQR [range]) proportions of
      visible needle tips were 83% (67-83 [50-100]%) for the textured Tuohy, 75% (67-83
      [33-83]%) for the textured single-shot needle and 33% (33-46 [0-50]%) for the
      smooth-surfaced Tuohy (p = 0.0007). Median (IQR [range]) needle shaft visibility
      was rated as 4.0 (3.5-4.7 [3.0-4.9]) for the textured Tuohy, 4.0 (3.8-4.5 [2.7
      4.9]) for the textured single-shot needle and 3.0 (2.4-3.3 [2.3-3.5]) for the
      smooth-surfaced Tuohy (p = 0.015). Nevertheless, visibility was reduced at wide
      angles in-plane and narrow angles out-of-plane both for needle tips (p = 0.004)
      and shafts (p = 0.005).

PMID- 25376432
TI  - Occupational exposure to blood and body fluids among health-care workers in
      Serbia.
AB  - OBJECTIVES: The aim of this study was to examine the epidemiology of occupational
      accidents and self-reported attitude of health-care workers (HCWs) in Serbia.
      SUBJECTS AND METHODS: A cross-sectional study was conducted among HCWs in
      selected departments of five tertiary care hospitals and in one secondary care
      hospital in February 2012. A previously developed self-administered questionnaire
      was provided to HCWs who had direct daily contact with patients. chi(2) test and
      Student's t test were used for statistical analysis of the data. RESULTS: Of the
      1,441 potential participants, 983 (68.2%) completed the questionnaire: 655
      (66.7%) were nurses/medical technicians, 243 (24.7%) were physicians and 85
      (8.6%) were other personnel. Of the 983 participants, 291 (29.6%) HCWs had had at
      least one accident during the previous year and 106 (40.2%) of them reported it
      to the responsible person. The highest prevalence (68.6%) of accidents was among
      nurses/technicians (p = 0.001). Accidents occurred more often in large clinical
      centers (81.1%; p < 0.001) and in the clinical ward, intensive care unit and
      operating theater (p = 0.003) than in other departments. Seventy-six (13.1%)
      nurses/medical technicians had an accident during needle recapping (p < 0.001).
      Of all the HCWs, 550 (55.9%) were fully vaccinated, including significantly more
      doctors (154, 63.4%) than participants from other job categories (p < 0.001).
      CONCLUSION: There was a relatively high rate of accidents among HCWs in our
      hospitals, most commonly amongst nurses and staff working in clinical wards,
      intensive care units and operating theaters. The most common types of accidents
      were needlestick injuries and accidents due to improper handling of contaminated
      sharp devices or occuring while cleaning instruments or by coming into contact
      with blood through damaged skin or through the conjunctiva/mucous membranes.

PMID- 25376433
TI  - Is it possible to strengthen psychiatric nursing staff's clinical supervision?
      RCT of a meta-supervision intervention.
AB  - AIM: To test the effects of a meta-supervision intervention in terms of
      participation, effectiveness and benefits of clinical supervision of psychiatric
      nursing staff. BACKGROUND: Clinical supervision is regarded as a central
      component in developing mental health nursing practices, but the evidence
      supporting positive outcomes of clinical supervision in psychiatric nursing is
      not convincing. DESIGN: The study was designed as a randomized controlled trial.
      All permanently employed nursing staff members at three general psychiatric wards
      at a Danish university hospital (n = 83) were allocated to either an intervention
      group (n = 40) receiving the meta-supervision in addition to attending usual
      supervision or to a control group (n = 43) attending usual supervision. METHODS:
      Self-reported questionnaire measures of clinical supervision effectiveness and
      benefits were collected at base line in January 2012 and at follow-up completed
      in February 2013. In addition, a prospective registration of clinical supervision
      participation was carried out over 3 months subsequent to the intervention.
      RESULTS: The main result was that it was possible to motivate staff in the
      intervention group to participate significantly more frequently in sessions of
      the ongoing supervision compared with the control group. However, more frequent
      participation was not reflected in the experienced effectiveness of the clinical
      supervision or in the general formative or restorative benefits. CONCLUSIONS: The
      intervention had a positive effect on individuals or wards already actively
      engaged in clinical supervision, which suggested that individuals and wards
      without well-established supervision practices may require more comprehensive
      interventions targeting individual and organizational barriers to clinical
      supervision.

PMID- 25376434
TI  - Preoperative inspiratory muscular training to prevent postoperative hypoxemia in
      morbidly obese patients undergoing laparoscopic bariatric surgery. A randomized
      clinical trial.
AB  - BACKGROUND: Morbidly obese patients show an increased risk of postoperative
      hypoxemia and pulmonary complications when compared with normal weight subjects.
      The purpose of this study was to determine the effects of preoperative
      inspiratory muscular training (IMT) on postoperative arterial oxygenation in
      morbidly obese patients submitted to laparoscopic bariatric surgery. METHODS:
      Forty-four morbidly obese patients were randomly assigned to receive either
      preoperative usual care (control group, n = 21) or preoperative IMT (trained
      group, n = 23) for a month prior to the date of surgery. Data on oxygenation
      (PaO2/FiO2 ratio) were obtained at 1 h and at 12 h after surgery (PACU 1 h and
      PACU 12 h, respectively). Data on maximum static inspiratory pressure (MIP) were
      obtained before and after the training period, and at postanesthesia care unit
      (PACU) 12-h time point. RESULTS: PaO2/FiO2 was significantly higher in the
      trained group than in the control group, both at PACU 1 h (305.2 +/- 77.6 vs.
      248.8 +/- 53.8, P = 0.008) and at PACU 12 h (333.5 +/- 59.6 vs. 289.7 +/- 79.6, P
      = 0.044). As a consequence, the percentage of patients with relative hypoxemia
      (PaO2/FiO2 lower than 300 mmHg) at the time of PACU discharge was higher in the
      control group (57 vs. 17 %, P: 0.006). MIP was significantly higher in the
      trained group compared with the control group at the preoperative time point
      (89.87 +/- 19.00 vs. 77.00 +/- 21.20 cm H2O, P = 0.04). CONCLUSIONS: Preoperative
      IMT improved postoperative oxygenation and increased inspiratory muscular
      strength in morbidly obese patients submitted to laparoscopic bariatric surgery.

PMID- 25376435
TI  - Basal and resting metabolic rates of physically disabled adult subjects: a
      systematic review of controlled cross-sectional studies.
AB  - AIM: To systematically review studies that investigated the basal metabolic rate
      (BMR) and resting metabolic rate (RMR) of physically disabled adult subjects.
      METHODS: The studies were identified via MedLine, Science Direct, Science Search,
      Scientific Electronic Library Online, Wiley, Latin American and Caribbean Health
      Sciences Literature, Cochrane, Indice Bibliografico Espanol de Ciencias de la
      Salud, Scopus, ProQuest Dissertations & Theses Database and System for
      Information on Grey Literature in Europe. No restriction on publication date was
      imposed. RESULTS: Data from 6 studies were included. The results showed that
      physically disabled adult subjects have a lower BMR and/or RMR compared to
      nondisabled subjects. However, the difference between the groups disappeared when
      the BMR and RMR were adjusted for fat-free mass. Due to the small number of
      studies on this subject and the limited types of physical disabilities evaluated
      in the literature, we could not make a definitive conclusion. CONCLUSIONS:
      Disabled individuals seem to have a lower absolute BMR and/or RMR than able
      bodied adults; however, this difference was not present or else it disappeared in
      half of the studies, after adjusting for body mass and/or fat-free mass.

PMID- 25376436
TI  - Effects of muscarinic receptor modulators on ocular biometry of guinea pigs.
AB  - PURPOSE: This study investigated whether pilocarpine and cyclopentolate induce
      changes in ocular biometry of guinea pigs, in order to understand if guinea pigs
      have a similar response to these two agents as humans do. METHODS: Under general
      anaesthesia, refraction, axial components and surface curvature in various
      optical interfaces of the eye were measured in 10 guinea pigs (age of 2 weeks) at
      baseline (0 min) and different time points (5, 10, 20, 30, 60, 90 min) after
      topical administration of pilocarpine or cyclopentolate. The interval between the
      two drug treatments for the same animals was at least 24 h. RESULTS: Eyes treated
      with pilocarpine developed approximately 6D myopia (p < 0.001 from 0 to 90 min)
      with a decrease in anterior lens radius of curvature (ALRC) (p < 0.001 from 0 to
      90 min, repeated measures anova). This myopic shift was moderately correlated to
      the decreased ALRC (r(2)  = 0.48, p < 0.001). Furthermore, a small but
      significant increase in the VCD (p < 0.001 from 0 to 30 min, repeated measures
      anova) with an unchanged AL (p = 0.85 from 0 to 90 min, repeated measures anova)
      after the drug treatment suggested a transient and mild forward movement of the
      lens. Cyclopentolate dilated the pupil in all eyes (p < 0.001 from 0 to 90 min,
      repeated measures anova) but did not change other ocular parameters. CONCLUSIONS:
      The muscarinic agonist, pilocarpine induced a myopic shift mainly due to a
      decrease in ALRC, suggesting that guinea pigs have an accommodative mechanism
      similar to that in humans. The minimal changes produced by cyclopentolate could
      be due to the use of general anaesthesia, which may have reduced the
      susceptibility of the eye to topical cyclopentolate in the induction of
      cycloplegia.

PMID- 25376438
TI  - Tube feeding: stopping more difficult than starting.

PMID- 25376437
TI  - Schottky-Gated Probe-Free ZnO Nanowire Biosensor.
AB  - A nanowire-based nanosensor for detecting biologically and chemically charged
      molecules that is probe-free and highly sensitive is demonstrated. The device
      relies on the nonsymmetrical Schottky contact under reverse bias, and is much
      more sensitive than the device based on the symmetric ohmic contact. This
      approach serves as a guideline for designing more practical chemical and
      biochemical sensors. 

PMID- 25376439
TI  - Effect of wine inhibitors on the proteolytic activity of papain from Carica
      papaya L. latex.
AB  - The influence of potential inhibitors naturally present in wine on the
      proteolytic activity of papain from Carica papaya latex was investigated to
      evaluate its applicability in white wine protein haze stabilization. Enzymatic
      activity was tested against a synthetic tripeptide chromogenic substrate in wine
      like acidic medium that consisted of tartaric buffer (pH 3.2) supplemented with
      ethanol, free sulfur dioxide (SO2 ), grape skin and seed tannins within the
      average ranges of concentrations that are typical in wine. The diagnosis of
      inhibition type, performed with the graphical method, demonstrated that all of
      tested wine constituents were reversible inhibitors of papain. The strongest
      inhibition was exerted by free SO2 , which acted as a mixed-type inhibitor,
      similar to grape skin and seed tannins. Finally, when tested in table white
      wines, the catalytic activity of papain, even when if it was ascribable to the
      hyperbolic behavior of Michaelis-Menten equation, was determined to be strongly
      affected by free SO2 and total phenol level.

PMID- 25376440
TI  - Do reciprocal associations exist between social and language pathways in
      preschoolers with autism spectrum disorders?
AB  - BACKGROUND: Differences in how developmental pathways interact dynamically in
      children with autism spectrum disorder (ASD) likely contribute in important ways
      to phenotypic heterogeneity. This study aimed to model longitudinal reciprocal
      associations between social competence (SOC) and language (LANG) pathways in
      young children with ASD. METHODS: Data were obtained from 365 participants aged 2
      4 years who had recently been diagnosed with an ASD and who were followed over
      three time points: baseline (time of diagnosis), 6- and 12 months later. Using
      structural equation modeling, a cross-lagged reciprocal effects model was
      developed that incorporated auto-regressive (stability) paths for SOC (using the
      Socialization subscale of the Vineland Adaptive Behavior Scales-2) and LANG
      (using the Preschool Language Scale-4 Auditory Comprehension subscale). Cross
      domain associations included within-time correlations and lagged associations.
      RESULTS: SOC and LANG were highly stable over 12 months. Small reciprocal cross
      lagged associations were found across most time points and within-time
      correlations decreased over time. There were no differences in strength of cross
      lagged associations between SOC-LANG and LANG-SOC across time points. Few
      differences were found between subgroups of children with ASD with and without
      cognitive impairment. CONCLUSIONS: Longitudinal reciprocal cross-domain
      associations between social competence and language were small in this sample of
      young children with ASD. Instead, a pattern emerged to suggest that the two
      domains were strongly associated around time of diagnosis in preschoolers with
      ASD, and then appeared to become more independent over the ensuing 12 months.

PMID- 25376441
TI  - Surface-mediated priming during in vitro generation of monocyte-derived dendritic
      cells.
AB  - Ex vivo-generated human dendritic cells (DC) are most commonly generated from
      monocytes using standard cell culture dishes. To elucidate the effect of the
      plastic surface during the differentiation process, we compared a standard
      adhesive plastic dish with four different mainly non-adherent surfaces. Untouched
      monocytes were cultured for 3 days in the presence of IL-4 and GM-CSF. Time-lapse
      videos were recorded, and the phenotype of the cells was analysed by flow
      cytometry. The cytokine profiles were analysed using a 25-plex cytokine assay.
      The use of non-adherent surfaces led to a significant reduction in expression of
      CD14 and CD38, and a significant increase in expression of CD86 compared to
      standard culture dishes. Expression levels of DC-SIGN and PD-L2 were reduced
      significantly on cells cultured on non-adherent surfaces. The cytokine production
      was independent on the surface used. The surface-mediated priming should
      therefore be considered when aiming to induce specific immune responses. This is
      especially important with regard to DC-based immunotherapy, where an adjustment
      of the surface during the DC generation process might have highly beneficial
      effects. 

PMID- 25376442
TI  - Revisiting antifungal prophylaxis in high-risk liver transplant recipients.

PMID- 25376443
TI  - Lung cancer.

PMID- 25376444
TI  - Optimization of exopolysaccharide production from Pseudomonas stutzeri AS22 and
      examination of its metal-binding abilities.
AB  - AIMS: To investigate the effect of culture conditions and medium components on
      exopolysaccharide (EPS) production by Pseudomonas stutzeri AS22 and to access the
      EPS performance as a metal-binding exopolysaccharide. METHODS AND RESULTS: The
      EPS production conditions of Ps. stutzeri AS22 in submerged culture were
      optimized using two approaches for EPS quantification, and its metal-binding
      capacity was evaluated using both single and mixed metal ions systems. Maximum
      EPS level was achieved after 24 h of incubation at 30 degrees C with an initial
      pH of 8.0, 250 rev min(-1) stirring level and 10% inoculum size. 50 g l(-1)
      starch, 5 g l(-1) yeast extract, 0.5 g l(-1) NaCl, 1.4 g l(-1) K2 HPO4, 0.4 g l(
      1) MgSO4, 0.4 g l(-1) CaCl2 and 1 g l(-1) mannose were found to be the most
      suitable carbon, nitrogen, mineral and additional carbohydrate sources,
      respectively. From metal-binding experiments, the crude EPS showed interesting
      metal adsorption capacity adopting the order Pb >> Co > Fe > Cu >> Cd. Lead was
      preferentially biosorbed with a maximal uptake of 460 mg g(-1) crude EPS.
      CONCLUSIONS: Under the optimal culture requirements, EPS level reached 10.2 g l(
      1) after 24 h of fermentation, seven times more than the production under initial
      conditions. According to the metal-binding assay, the crude EPS has potential to
      be used as a novel biosorbent in the treatment of heavy metals-contaminated
      water. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results are interesting in terms
      of yield as well as efficiency for the potential use of the Ps. stutzeri
      exopolysaccharide as a metal-absorbent polymer in the bioremediation field.

PMID- 25376446
TI  - Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic
      containers and the question of human exposure.
AB  - Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer to render
      poly(vinyl chloride) (PVC) soft and malleable. Plasticized PVC is used in
      hospital equipment, food wrapping, and numerous other commercial and industrial
      products. Unfortunately, plasticizers can migrate within the material and leach
      out of it over time, ending up in the environment and, frequently, the human
      body. DEHP has come under increased scrutiny as its breakdown products are
      believed to be endocrine disruptors and more toxic than DEHP itself. DEHP and its
      breakdown products have been identified as ubiquitous environmental contaminants,
      and daily human exposure is estimated to be in the microgram per kilogram level.
      The objective of this review is to summarize and comment on published sources of
      DEHP exposure and to give an overview of its environmental fate. Exposure through
      bottled water was examined specifically, as this concern is raised frequently,
      yet only little exposure to DEHP occurs through bottled water, and DEHP exposure
      is unlikely to stem from the packaging material itself. Packaged food was also
      examined and showed higher levels of DEHP contamination compared to bottled
      water. Exposure to DEHP also occurs in hospital environments, where DEHP leaches
      directly into liquids that passed through PVC/DEHP tubing and equipment. The
      latter exposure is at considerably higher levels compared to food and bottled
      water, specifically putting patients with chronic illnesses at risk. Overall,
      levels of DEHP in food and bottled water were below current tolerable daily
      intake (TDI) values. However, our understanding of the risks of DEHP exposure is
      still evolving. Given the prevalence of DEHP in our atmosphere and environment,
      and the uncertainty revolving around it, the precautionary principle would
      suggest its phaseout and replacement. Increased efforts to develop viable
      replacement compounds, which necessarily includes rigorous leaching, toxicity,
      and impact assessment studies, are needed before alternative plasticizers can be
      adopted as viable replacements. 

PMID- 25376445
TI  - [Eleven years of core data set in intensive care medicine. Severity of disease
      and workload are increasing].
AB  - BACKGROUND: In the year 2000 a working group of the German Interdisciplinary
      Association for Intensive Care Medicine (DIVI) defined a core data set on quality
      assurance for the first time. In the following years the participating intensive
      care units sent data to the registry on a voluntary basis and received an annual
      report on benchmarking data. Alterations in the quality in the field of intensive
      care medicine have so far only been published to a very low extent. AIM: This
      study analyzed the core date set of the DIVI between 2000 and 2010 in respect to
      changes in disease severity using the simplified acute physiology score (SAPS
      II), the sequential organ failure assessment (SOFA), the need for therapeutic
      interventions with the therapeutic intervention scoring system (TISS 28) and
      intensive care unit (ICU) mortality. MATERIAL AND METHODS: Inclusion criteria
      were participation in the registry for at least 4 years, SAPS II, SOFA, TISS28
      scores available and data on ICU discharge. A standardized mortality rate (SMR)
      was calculated for each year. RESULTS: The mean SAPS II score including 94,398
      patients increased by 0.23 points/year with a standard error (SE) of 0.02 to 26.9
      +/- 12 points (p < 0.001). Similarly, the SOFA score on admission to the ICU
      increased by 0.14 points/year (SE 0.04) to 3.4 +/- 2.7 points (p < 0.001), the
      proportion of patients with a two organ failure doubled to 7.1 % and the number
      of patients dependent on ventilation increased by 13.6 % to 59.8 %. The mean time
      on ventilation increased by 0.17 ventilator days/year (SE 0.01, p < 0.001) to 3.1
      +/- 7.5 days/patient. The mean number of therapeutic interventions increased by
      8.7 % to 26.3 +/- 8.3 TISS 28 points/day. The mean length of stay on the ICU (4.3
      +/- 8 days) and the age of the patients (63.2 +/- 17.0 years) remained unchanged.
      The readmission rate showed no significant changes between the years 2004 and
      2010. The readmission rate to the ICU within 48 h after primary discharge was 3.1
      % with a 95 % confidence interval (CI) of 3.0-3.3 in contrast to 1.5 % (95 % CI
      1.4-1.6) for readmission to the ICU after 48 h. The length of stay in hospital
      before admission to the ICU decreased for patients with scheduled surgery (6.3 +/
      9.7 days vs. 4.2 +/- 6.9 days), increased slightly for patients with medically
      indicated admission to the ICU (2.4 +/- 8.2 days 3.1 +/- 8.6 days) and remained
      unchanged for patients with unscheduled admission to the ICU after surgery (4.1
      +/- 8.6 days). The SMR decreased between 2000 and 2004 from 0.97 to 0.72 and
      increased again thereafter to 0.99 (ICU mortality 8.5 %). CONCLUSION: The
      severity of disease on admission to the ICU, the proportion of patients on
      ventilation and the workload of therapeutic interventions increased between 2000
      and 2010 in German ICUs but the length of stay of patients in the ICU remained
      unchanged. The SMR decreased until 2005 and increased thereafter to return to the
      initial values. The overall ICU mortality was low compared to international data.

PMID- 25376447
TI  - Clinical usefulness of diquafosol for real-world dry eye patients: a prospective,
      open-label, non-interventional, observational study.
AB  - INTRODUCTION: This study was designed to evaluate the efficacy and safety of 3%
      diquafosol ophthalmic solution in dry eye patients in clinical practice. METHODS:
      Subjects were dry eye patients who had never used diquafosol, and observation was
      conducted prospectively over 2 months. The corneal and conjunctival fluorescein
      staining score, tear film break-up time, 12 dry eye-related subjective symptoms,
      patient-reported outcomes, and adverse events were investigated. RESULTS: Data
      were collected from 465 medical institutions for 3,196 patients. Diquafosol led
      to significant improvement in all subjective symptoms and objective findings (P <
      0.001, paired t test). Diquafosol was effective regardless of the degree of
      severity according to the corneal and conjunctival fluorescein staining score or
      therapeutic pattern. Overall, 76.0% patients responded that their condition had
      improved. Adverse reactions were observed in 6.3% of patients. The major adverse
      reactions were eye discharge, eye irritation, and eye pain. CONCLUSION:
      Diquafosol was effective for various dry eye patients in clinical practice, and
      no significant safety-related problems occurred.

PMID- 25376448
TI  - Pruritus and quality of life in moderate-to-severe plaque psoriasis: post hoc
      explorative analysis from the PRISTINE study.
AB  - BACKGROUND: Pruritus is a clinically important symptom of psoriasis that has a
      major impact on quality of life (QoL). OBJECTIVE: The objective of this study was
      to examine pruritus and QoL in patients with moderate-to-severe psoriasis treated
      with etanercept (ETN) in the PRISTINE clinical trial. METHODS: Patients were
      randomized (1 : 1, double-blind) to ETN 50 mg QW or 50 mg BIW for 12 weeks,
      followed by 50 mg QW for 12 weeks. Pruritus was reported as 0 (no itching) to 5
      (severe itching). Associations were examined between pruritus and Psoriasis Area
      and Severity Index, Dermatology Life Quality Index (DLQI), Hospital Anxiety and
      Depression Screening (HADS), Functional Assessment of Chronic Illness Therapy
      Fatigue (FACIT-Fatigue), Euro-Qol 5D (EQ-5D) and Medical Outcomes Study (MOS)
      Sleep Index II. RESULTS: At baseline, patients (n = 270) had a mean pruritus
      level of 3.6. Itching (level >=1) was reported by 96% of patients, 62% of whom
      had severe itching (level >=4) and 26% had the highest level of itching. DLQI,
      HADS-Anxiety, HADS-Depression, FACIT-Fatigue, EQ-5D visual analog scale, and MOS
      Sleep Index II were significantly associated with itch. At week 12, mean pruritus
      improvement in the ETN BIW/QW group was greater than in the QW/QW group (2.4 vs.
      1.6, P < 0.001), but not at week 24 (2.2 vs. 2.0, P = 0.180). Patients with the
      most severe itching at baseline (score of 5) had a mean score of 1.7 at week 24.
      Overall, patients with clinically meaningful pruritus improvement at week 24
      reported greater improvement in QoL measures than other patients. CONCLUSION:
      Most patients with moderate-to-severe psoriasis in this study (96%) reported
      pruritus. Pruritus improved significantly with ETN therapy and was strongly
      associated with improvements in QoL. These data support the clinical relevance of
      pruritus as an important symptom of patients with moderate/severe psoriasis.

PMID- 25376449
TI  - Project JOINTS: what factors affect bundle adoption in a voluntary quality
      improvement campaign?
AB  - BACKGROUND: Diffusion and adoption of effective evidence-based clinical practices
      can be slow, especially if complex changes are required to implement new
      practices. OBJECTIVE: To examine how hospital adherence to quality improvement
      (QI) methods and hospital engagement with a large-scale QI campaign could
      facilitate the adoption of an enhanced prevention bundle designed to reduce
      surgical site infection (SSI) rates after orthopaedic surgery (hip and knee
      arthroplasty). METHODS: We conducted telephone interviews with hospital QI
      leaders from 73 of the 109 hospitals (67% response rate) in five states that
      participated in Project JOINTS (Joining Organizations IN Tackling SSIs), a QI
      campaign run by Institute for Healthcare Improvement (IHI). Using QI methods
      grounded in the IHI Model for Improvement, this campaign encouraged hospitals to
      implement an enhanced SSI prevention bundle. Hospital QI leaders reported on
      their hospital's adherence to the Project JOINTS QI methods; their level of
      engagement with Project JOINTS activities; and adoption of the SSI prevention
      bundle components. Interview data were analysed quantitatively and qualitatively.
      RESULTS: Both adherence to the QI methods and hospital engagement were positively
      associated with complete bundle adoption. Hospital engagement, especially the use
      of project materials and tools, was also positively associated with the
      initiation of and improved adherence to individual bundle components.
      CONCLUSIONS: Our findings suggest that greater adherence to the QI methods and
      active hospital engagement in a QI campaign facilitate adoption of evidence-based
      patient safety bundles in orthopaedic practice.

PMID- 25376450
TI  - [Bleeding complications under oral anticoagulation].

PMID- 25376451
TI  - Methodology and design of a national epidemiological study on adult neuromuscular
      disease.
AB  - BACKGROUND: There have been no previous population-based studies of adult
      neuromuscular disease (NMD) in the Republic of Ireland (RoI). This article
      describes methods and case-ascertainment strategies used to identify patients
      with inherited and acquired NMD for the purpose of obtaining the prevalence of
      these disorders in the RoI. METHODS: This epidemiological study was conducted
      between January 2012 and January 2014. Prospective and retrospective (until 1990)
      case identification of adults with inherited and acquired NMD have been carried
      out. Multiple countrywide patient identification sources including neuromuscular
      clinics, hospital neurology databases, the hospital in-patient enquiry (HIPE)
      system of each hospital and the records of Muscular Dystrophy Ireland, a
      nonprofit organisation, were used. RESULTS: In total, 3,724 potential cases were
      identified. Of these, 1,083 were excluded because 869 cases represented
      duplicates or triplicates, 133 were coded incorrectly in HIPE, 74 patients were
      deceased and 7 patients had moved out of the country. The highest number of cases
      was identified in neurology databases and HIPE (1,724 and 884, respectively). A
      total of 2,641 individuals fulfilled the inclusion criteria and were included in
      the study. CONCLUSION: Detailed epidemiological data of this nature is difficult
      to acquire in the current structure of the Irish health service, requiring
      multiple sources including input from voluntary patient organisations. The
      development of a national patient registry for some or all of these conditions
      would greatly facilitate standardised data recording, giving a true picture of
      the burden of neuromuscular diseases in a population.

PMID- 25376452
TI  - Erratum to: Difficult peritonitis cases in children undergoing chronic peritoneal
      dialysis: relapsing, repeat, recurrent and zoonotic episodes.

PMID- 25376453
TI  - Risk for borderline ovarian tumours after exposure to fertility drugs: results of
      a population-based cohort study.
AB  - STUDY QUESTION: Do fertility drugs increase the risk for borderline ovarian
      tumours, overall and according to histological subtype? SUMMARY ANSWER: The use
      of any fertility drug did not increase the overall risk for borderline ovarian
      tumours, but an increased risk for serous borderline ovarian tumours was observed
      after the use of progesterone. WHAT IS KNOWN ALREADY: Many epidemiological
      studies have addressed the connection between fertility drugs use and risk for
      ovarian cancer; most have found no strong association. Fewer studies have
      assessed the association between use of fertility drugs and risk for borderline
      ovarian tumours, and the results are inconsistent. STUDY DESIGN, SIZE, DURATION:
      A retrospective case-cohort study was designed with data from a cohort of 96 545
      Danish women with fertility problems referred to all Danish fertility clinics in
      the period 1963-2006. All women were followed for first occurrence of a
      borderline ovarian tumour from the initial date of infertility evaluation until a
      date of migration, date of death or 31 December 2006, whichever occurred first.
      The median length of follow-up was 11.3 years. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Included in the analyses were 142 women with borderline ovarian tumours
      (cases) and 1328 randomly selected sub-cohort members identified in the cohort
      during the follow-up through 2006. Cases were identified by linkage to the Danish
      Cancer Register and the Danish Register of Pathology by use of personal
      identification numbers. To obtain information on use of fertility drugs, hospital
      files and medical records of infertility-associated visits to all Danish
      fertility clinics were collected and supplemented with information from the
      Danish IVF register. We used case-cohort techniques to calculate rate ratios
      (RRs) and corresponding 95% confidence intervals (CIs) for borderline ovarian
      tumours, overall and according to histological subtype, associated with the use
      of any fertility drug or five specific groups of fertility drugs: clomiphene
      citrate, gonadotrophins (human menopausal gonadotrophins and follicle-stimulating
      hormone), gonadotrophin-releasing hormone analogues, human chorionic
      gonadotrophins and progesterone. MAIN RESULTS AND THE ROLE OF CHANCE: Analyses
      within the cohort showed that the overall risk for borderline ovarian tumours was
      not associated with the use of any fertility drug (RR 1.00; 95% CI 0.67-1.51) or
      of gonadotrophins (RR 1.32; 95% CI 0.81-2.14), clomiphene citrate (RR 0.96; 95%
      CI 0.64-1.44), human chorionic gonadotrophins (RR 0.91; 95% CI 0.61-1.36) or
      gonadotrophin-releasing hormone analogues (RR 1.10; 95% CI 0.66-1.81).
      Furthermore, no associations were observed between the risk for borderline
      ovarian tumours and these groups of fertility drugs according to the number of
      cycles of use, length of follow-up or parity. In contrast, use of progesterone
      increased the risk for borderline ovarian tumours, particularly serous tumours,
      for which statistically significantly increased risks were observed with any use
      of progesterone (RR 1.82; 95% CI 1.03-3.24), among women treated with >=4 cycles
      of progesterone (RR 2.63; 95% CI 1.04-6.64) and for all women followed up for >=4
      years after their first treatment with progesterone. LIMITATIONS, REASONS FOR
      CAUTION: Although we tried to minimize the effects of the underlying infertility,
      the severity of infertility might have affected our risk estimates, as women with
      more severe fertility problems may receive more treatment. The results from the
      subgroup analyses, e.g. the findings of an elevated risk for borderline ovarian
      tumours associated with increased time since first use of progesterone and with
      increased number of treatment cycles, should be interpreted with caution as these
      analyses are based on a limited number of women with borderline ovarian tumours.
      WIDER IMPLICATIONS OF THE FINDINGS: Although this study, which is the largest to
      date, provides reassuring evidence that there is no strong link between the use
      of fertility drugs and risk for borderline ovarian tumours, the novel observation
      of an increased risk for serous tumours after use of progesterone should be
      investigated in large epidemiological studies. The results of the present study
      provide valuable knowledge for clinicians and other health care personnel
      involved in the diagnosis and treatment of fertility problems. STUDY
      FUNDING/COMPETING INTERESTS: No conflict of interest was reported. S.M.B. was
      supported by a research scholarship from the Danish Cancer Society.

PMID- 25376454
TI  - Protein oxidative stress markers in peritoneal fluids of women with deep
      infiltrating endometriosis are increased.
AB  - STUDY QUESTION: Are protein oxidative stress markers [thiols, advanced oxidation
      protein products (AOPP), protein carbonyls and nitrates/nitrites] in
      perioperative peritoneal fluid higher in women with histologically proven
      endometriosis when compared with endometriosis-free controls? SUMMARY ANSWER:
      Protein oxidative stress markers are significantly increased in peritoneal fluids
      from women with deep infiltrating endometriosis with intestinal involvement when
      compared with endometriosis-free controls. WHAT IS KNOWN ALREADY: Endometriosis
      is a common gynaecologic condition characterized by an important inflammatory
      process. Various source of evidence support the role of oxidative stress in the
      development of endometriosis. STUDY DESIGN, SIZE, DURATION: We conducted a
      prospective laboratory study in a tertiary-care university hospital between
      January 2011 and December 2012, and included 235 non-pregnant women, younger than
      42 year old, undergoing surgery for a benign gynaecological condition.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: After complete surgical exploration of
      the abdomino-pelvic cavity, 150 women with histologically proven endometriosis
      and 85 endometriosis-free controls women were enrolled. Women with endometriosis
      were staged according to a surgical classification in three different phenotypes
      of endometriosis: superficial peritoneal endometriosis (SUP), ovarian
      endometrioma (OMA) and deeply infiltrating endometriosis (DIE). Perioperative
      peritoneal fluids samples were obtained from all study participants. Thiols,
      AOPP, protein carbonyls and nitrates/nitrites were assayed in all peritoneal
      samples. MAIN RESULTS AND THE ROLE OF CHANCE: Concentrations of peritoneal AOPP
      were significantly higher in endometriosis patients than in the control group
      (median, 128.9 umol/l; range, 0.3-1180.1 versus median, 77.8 umol/l; range, 0.8
      616.1; P < 0.001). In a similar manner concentrations of peritoneal
      nitrates/nitrites were higher in endometriosis patients than in the control group
      (median, 24.8 umol/l; range, 1.6-681.6 versus median, 18.5 umol/l; range, 1.6
      184.5; P < 0.05). According to the surgical classification, peritoneal fluids
      protein AOPP and nitrates/nitrites were significantly increased only in DIE
      samples when compared with controls (P < 0.001 and P < 0.05; respectively),
      whereas the others forms of endometriosis (SUP and OMA) showed non-statistically
      significant increases. We found positive correlations between peritoneal fluids
      AOPP concentrations, nitrites/nitrates levels and the total number of intestinal
      DIE lesions (r = 0.464; P < 0.001 and r = 0.366; P = 0.007; respectively).
      LIMITATIONS, REASONS FOR CAUTION: Inclusion of only surgical patients may
      constitute a possible selection bias. In fact, our control group involved women
      who underwent surgery for benign gynaecological conditions. This specificity of
      our control group may lead to biases stemming from the fact that some of these
      conditions, such as fibroids, ovarian cysts or tubal infertility, might be
      associated with altered peritoneal proteins oxidative stress markers. WIDER
      IMPLICATIONS OF THE FINDINGS: We demonstrate the existence of a significantly
      increased protein oxidative stress status in peritoneal fluid from women with
      endometriosis especially in cases of DIE with intestinal involvement. This study
      opens the way to future more mechanistics studies to determine the exact role of
      protein oxidative stress in the pathogenesis of endometriosis. Even if an
      association does not establish proof of cause and effect, these intrinsic
      biochemical characteristics of endometriosis may lead to the evaluation of
      therapeutic approaches targeting oxidative imbalance. STUDY FUNDING/COMPETING
      INTERESTS: No funding was used for this study. The authors have no conflict of
      interest.

PMID- 25376455
TI  - Terminology for pregnancy loss prior to viability: a consensus statement from the
      ESHRE early pregnancy special interest group.
AB  - Pregnancy loss prior to viability is common and research in the field is
      extensive. Unfortunately, terminology in the literature is inconsistent. The lack
      of consensus regarding nomenclature and classification of pregnancy loss prior to
      viability makes it difficult to compare study results from different centres. In
      our opinion, terminology and definitions should be based on clinical findings,
      and when possible, transvaginal ultrasound. With this Early Pregnancy Consensus
      Statement, it is our goal to provide clear and consistent terminology for
      pregnancy loss prior to viability. 

PMID- 25376456
TI  - Pregnancy outcome and long-term follow-up after in vitro fertilization in women
      with renal transplantation.
AB  - STUDY QUESTION: What is the child morbidity after IVF in women who have received
      a kidney transplant? SUMMARY ANSWER: Overall, obstetric outcome and morbidity in
      children of women who had undergone renal transplantation and IVF treatment were
      favourable. WHAT IS KNOWN ALREADY: There are several studies of the obstetric
      outcome in women with spontaneous conception after solid organ transplantation as
      well as studies of obstetric outcome after IVF in general. There are only a few
      case reports of women with kidney or pancreas-kidney transplantation and
      deliveries after IVF treatment. STUDY DESIGN, SIZE, DURATION: A population-based
      retrospective register study was carried out in Sweden including all women with
      solid organ transplantation and deliveries after IVF; however, only women with
      kidney transplants were recruited. It also included information on all singleton
      deliveries after kidney transplantation and spontaneous conception between 1973
      and 2012. PARTICIPANTS/MATERIALS, SETTING AND METHODS: We cross-linked the IVF
      registers with the Medical Birth Register, the Patient Register and the Cause of
      Death Register. Study group 1 consisted of women with kidney transplantation and
      deliveries after IVF treatment. Study group 2 consisted of women with kidney
      transplantation and singleton deliveries after spontaneous conception. Group 3
      (control group to singletons in study group 1) consisted of women without organ
      transplantation and with singleton deliveries after IVF, matched for maternal
      age, parity and date of birth. Group 4 (control group to study group 2) consisted
      of women without organ transplantation and with singleton deliveries after
      spontaneous conception, matched for maternal age, parity and year of birth. MAIN
      RESULTS AND THE ROLE OF CHANCE: Seven singletons and one set of twins were born
      after organ transplantation and IVF. All women in this group had renal
      transplants. Among singletons, two (28.6%) were preterm births (PTB), one (14.3%)
      had very low birthweight (VLBW) (672 g) and one (14.3%) was small for gestational
      age (SGA). Two infants had minor birth defects. One woman developed pre-eclampsia
      (14.3%). Mean age at follow-up of the children was 9.7 years (SD 4.2). Two
      children were diagnosed with hyperactivity disorders. There were 199 singletons
      born after renal transplantation and spontaneous conception. The rates of pre
      eclampsia (23.6%), PTB (48.5%), LBW (43.7%) and SGA (21.2%) were significantly
      higher in pregnancies of women with renal transplants who had conceived
      spontaneously than in pregnancies where there was no transplantation and
      conception was spontaneous. Neonatal morbidity, early neonatal and infant
      mortality were all significantly higher. No increase in birth defects was seen.
      Mean age at follow-up of the children was 14.7 years (SD 9.4). Acute bronchitis,
      systemic lupus erythematosus and hyperactivity disorders were more common in
      children delivered to women with renal transplantation than in children delivered
      to women with no transplanted organs. Otherwise, long-term child morbidity was
      comparable. LIMITATIONS, REASONS FOR CAUTION: The women who had received renal
      transplants and who had given birth after IVF were a small group and may
      represent a selected group of comparatively healthy women. WIDER IMPLICATIONS OF
      THE FINDINGS: The results are important to transplant recipients with infertility
      problems. Neonatal outcomes after maternal renal transplantation and spontaneous
      conception were in agreement with the literature. Long-term follow-up of this
      group of children has long been asked for and findings are included in this
      report. STUDY FUNDING/COMPETING INTERESTS: No conflict of interest was reported.
      The study was supported by grants from Swedish Association of Local Authorities
      and Regions and by grants from the University of Gothenburg/Sahlgrenska
      University hospital (LUA/ALF 70940).

PMID- 25376457
TI  - No evidence for mutations in NLRP7, NLRP2 or KHDC3L in women with unexplained
      recurrent pregnancy loss or infertility.
AB  - STUDY QUESTION: Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing
      protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent
      pregnancy loss (RPL) or infertility? SUMMARY ANSWER: We found no evidence for
      mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility. WHAT IS KNOWN
      ALREADY: Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform
      moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with
      the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome
      (BWS). STUDY DESIGN, SIZE, AND DURATION: Ninety-four patients with well
      characterized, unexplained infertility were recruited over a 9-year period from
      three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more
      consecutive miscarriages of unknown etiology were provided by the Recurrent
      Miscarriage Clinic at St Mary's Hospital, London, UK. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Patients were recruited into both cohorts following extensive
      clinical studies. Genomic DNA was isolated from peripheral blood and subject to
      Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were
      analyzed by Sequencher v5.0 software and variants compared with those observed in
      the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap
      databases. Functional effects of non-synonymous variants were predicted using
      Polyphen-2 and sorting intolerant from tolerant (SIFT). MAIN RESULTS AND THE ROLE
      OF CHANCE: No disease-causing mutations were identified in NLRP2, NLRP7 and
      KHDC3L in our cohorts of unexplained infertility and RPL. LIMITATIONS, REASONS
      FOR CAUTION: Due to the limited patient size, it is difficult to conclude if the
      low frequency single nucleotide polymorphisms observed in the present study are
      causative of the phenotype. The design of the present study therefore is only
      capable of detecting highly penetrant mutations. WIDER IMPLICATIONS OF THE
      FINDINGS: The present study supports the hypothesis that mutations in NLRP7 and
      KHDC3L are specific for the BiHM phenotype and do not play a role in other
      adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only
      been associated with the imprinting disorder BWS in offspring and there is no
      evidence for a role in molar pregnancies, RPL or unexplained infertility. STUDY
      FUNDING/COMPETING INTERESTS: This study was funded by the following sources:
      Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise
      Estonia (Grant EU30020); Mentored Resident research project (Department of
      Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical
      Research Centre; Grant Number C06RR029965 from the National Center for Research
      Resources (NCCR; NIH). No competing interests declared.

PMID- 25376459
TI  - Which set of embryo variables is most predictive for live birth? A prospective
      study in 6252 single embryo transfers to construct an embryo score for the
      ranking and selection of embryos.
AB  - STUDY QUESTION: Which embryo score variables are most powerful for predicting
      live birth after single embryo transfer (SET) at the early cleavage stage?
      SUMMARY ANSWER: This large prospective study of visual embryo scoring variables
      shows that blastomere number (BL), the proportion of mononucleated blastomeres
      (NU) and the degree of fragmentation (FR) have independent prognostic power to
      predict live birth. WHAT IS KNOWN ALREADY: Other studies suggest prognostic
      power, at least univariately and for implantation potential, for all five
      variables. A previous study from the same centre on double embryo transfers with
      implantation as the end-point resulted in the integrated morphology cleavage
      (IMC) score, which incorporates BL, NU and EQ. STUDY DESIGN, SIZE AND DURATION: A
      prospective cohort study of IVF/ICSI SET on Day 2 (n = 6252) during a 6-year
      period (2006-2012). The five variables (BL NU, FR, EQ and symmetry of cleavage
      (SY)) were scored in 3- to 5-step scales and subsequently related to clinical
      pregnancy and LBR. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 4304
      women undergoing IVF/ICSI in a university-affiliated private fertility clinic
      were included. Generalized estimating equation models evaluated live birth
      (yes/no) as primary outcome using the embryo variables as predictors. Odds ratios
      with 95% confidence intervals and P-values were presented for each predictor. The
      C statistic (i.e. area under receiver operating characteristic curve) was
      calculated for each model. Model calibration was assessed with the Hosmer
      Lemeshow test. A shrinkage method was applied to remove bias in c statistics due
      to over-fitting. MAIN RESULTS AND THE ROLE OF CHANCE: LBR was 27.1% (1693/6252).
      BL, NU, FR and EQ were univariately highly significantly associated with LBR. In
      a multivariate model, BL, NU and FR were independently significant, with c
      statistic 0.579 (age-adjusted c statistic 0.637). EQ did not retain significance
      in the multivariate model. Prediction model calibration was good for both
      pregnancy and live birth. We present a ranking tree with combinations of values
      of the BL, NU and FR embryo variables for optimal selection of the embryo/s to
      transfer, providing a revised IMC score. The five embryo variables had similar
      effects over all age groups. LIMITATIONS, REASONS FOR CAUTION: Limitations of the
      present study are those inherent for real-time visual scoring, including risks of
      inter-observer variation and the hazards of fixed time-point scoring procedures
      in a dynamic process. The study is restricted to Day-2 transfers. WIDER
      IMPLICATIONS OF THE FINDINGS: To our knowledge this is the largest prospective,
      SET study performed with the explicit aim of constructing an evidence-based
      embryo score for the ranking and selection of early cleavage stage embryos. In
      line with previous research, our data suggest that the symmetry of cleavage
      variable may be omitted when scoring embryos in the early cleavage stage. We
      suggest that, following validation in other populations, the revised IMC score
      may be used when international standards for embryo scoring are discussed. STUDY
      FUNDING/COMPETING INTEREST: Carl von Linne Clinic, Uppsala and the Department of
      Women's and Children's Health and the Family Planning Fund in Uppsala, Uppsala
      University, Uppsala, Sweden financed this study. There are no competing interests
      to declare.

PMID- 25376458
TI  - Inhibitor of apoptosis proteins (IAPs) may be effective therapeutic targets for
      treating endometriosis.
AB  - STUDY QUESTION: What is the role of the inhibitor of apoptosis proteins (IAPs) in
      human endometriotic tissues and a mouse model of endometriosis? SUMMARY ANSWER:
      Four IAP proteins were expressed in endometriotic tissue indicating IAPs may be a
      key factor in the pathogenesis and progression of endometriosis. WHAT IS KNOWN
      ALREADY: Overexpression of IAPs protects against a number of proapoptotic
      stimuli. IAPs (c-IAP1, c-IAP2, XIAP and Survivin) are expressed in human ectopic
      endometrial stromal cells (ESCs) from ovarian endometriomas. STUDY DESIGN, SIZE,
      DURATION: Forty-eight women with or without ovarian endometrioma are included in
      this study. BALB/c mice (n = 24) were used for the mouse endometriosis model.
      Mice with surgically induced endometriosis were treated with an IAP antagonist
      (BV6) for 4 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human ectopic
      endometrial tissues from chocolate cysts and eutopic endometrial tissue were
      collected. ESCs were enzymatically isolated from these tissues. ESC proliferation
      was examined by 5-bromo-2'-deoxyuridine-enzyme-linked immunosorbent assay. IAPs
      expression in tissue derived from eutopic endometria and chocolate cysts was
      evaluated using real-time RT-PCR and immunohistochemistry. A homologous mouse
      endometriosis model was established by transplanting donor mouse uterine tissue
      into the abdominal cavities of recipient mice. After treating the mice with BV6
      (i.p. 10 mg/ml), the extent of endometriosis-like lesions in mice was measured
      and proliferative activity assessed by Ki67 staining. All experiments were
      repeated a minimum of three times. MAIN RESULTS AND THE ROLE OF CHANCE: IAP (c
      IAP1, c-IAP2, XIAP and Survivin) mRNA and protein in human ectopic endometrial
      tissues were expressed at higher levels than in eutopic endometrial tissues (P <
      0.05). All four IAPs proteins were expressed in mouse endometriosis-like
      implants. BV6 inhibited BrdU incorporation of human ESCs (P < 0.05 versus
      control). BV6 also decreased the total number, weight, surface area and Ki67
      positive cells in the endometriosis-like lesions in the mice (P < 0.05 versus
      control). LIMITATIONS, REASONS FOR CAUTION: Endometriotic lesions were surgically
      induced in mice by transplanting mouse uterine tissue only, not human
      pathological endometriotic tissue. Furthermore, the effects of BV6 on human ESCs
      and mouse endometriosis-like lesions may differ between the species. WIDER
      IMPLICATIONS OF THE FINDINGS: Our data support the hypothesis that IAPs are
      involved in the development of endometriosis, and therefore an inhibitor of IAPs
      has potential as a novel treatment for endometriosis. STUDY FUNDING/COMPETING
      INTERESTS: This work was supported by KAKENHI (Japan Society for the Promotion of
      Science, Grant-in-Aid: to F.T.; 21592098 and to T.H.; 24659731) and Yamaguchi
      Endocrine Research Foundation. The authors have no conflicts of interest to
      disclose.

PMID- 25376460
TI  - Repair of congenital 'disconnected uterus': a new female genital anomaly?
AB  - Congenital uterine anomaly is a female genital disorder caused by developmental
      anomaly of the Mullerian ducts. In this report, we present a case of repair of
      congenital 'disconnected uterus' between the cervix and the body of the uterus.
      The case did not correspond to the consensus classifications that have been
      proposed for congenital uterine anomaly. The patient was a young woman whose
      chief complaints were not having first menstruation and experiencing monthly
      severe lower abdominal pain. Magnetic resonance imaging showed that the uterine
      body was separated from the uterine cervix. Uteroplasty was conducted to
      anastomose the separated uterus. Periodic menstruation started 1 month after
      surgery and abdominal pain was improved. Performance of uteroplasty in this case
      was extremely significant and greatly improved the quality of life of the
      patient. 

PMID- 25376461
TI  - Treatment with Ca2+ ionophore improves embryo development and outcome in cases
      with previous developmental problems: a prospective multicenter study.
AB  - STUDY QUESTION: Does calcium ionophore treatment (A23187, calcimycin) improve
      embryo development and outcome in patients with a history of developmental
      problems/arrest? SUMMARY ANSWER: Application of A23187 leads to increased rates
      of cleavage to 2-cell stage, blastocyst formation and clinical pregnancy/live
      birth. WHAT IS KNOWN ALREADY: Studies on lower animals indicate that changes in
      intracellular free calcium trigger and regulate the events of cell division. In
      humans, calcium fluctuations were detected with a peak shortly before cell
      division. Interestingly, these calcium oscillations disappeared in arrested
      embryos. Mitotic division blocked with a Ca(2+) chelator could be restored by
      means of ionophores in an animal model. STUDY DESIGN, SIZE, DURATION: This
      prospective, multicenter (five Austrian centers), uncontrolled intervention study
      (duration 1 year) includes 57 patients who provided informed consent.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria were complete embryo
      developmental arrest in a previous cycle (no transfer), complete developmental
      delay (no morula/blastocyst on Day 5), or reduced blastocyst formation on Day 5
      (<=15%). Severe male factor patients and patients with <30% fertilization rate
      after ICSI were excluded because these would be routine indications for ionophore
      usage. The total of the 57 immediately preceding cycles in the same patients
      constituted the control cycles/control group. In the treatment cycles, all
      metaphase II-oocytes were exposed to a commercially available ready-to-use
      ionophore for 15 min immediately after ICSI. After a three-step washing
      procedure, in vitro culture was performed as in the control cycles, up to
      blastocyst stage when achievable. MAIN RESULTS AND THE ROLE OF CHANCE:
      Fertilization rate did not differ (75.4 versus 73.2%); however, further cleavage
      to 2-cell stage was significantly higher (P < 0.001) in the ionophore group
      (98.5%) when compared with the control cycles (91.9%). In addition, significantly
      more (P < 0.05) blastocysts formed on Day 5 in the study compared with the
      control group (47.6 versus 5.5%, respectively) and this was associated with a
      significant increase (P < 0.01) in the rates of implantation (44.4 versus 12.5%),
      clinical pregnancy (45.1 versus 12.8%) and live birth (45.1 versus 12.8%). All
      babies born at the time of writing (22/28) were healthy. LIMITATIONS, REASONS FOR
      CAUTION: The frequency of patients showing embryo developmental problems was
      expected to be low; therefore, a multicenter approach was chosen in order to
      increase sample size. In one-third of the cycles, the clinician or patient
      requested a change of stimulation protocol; however, this did not influence the
      developmental rate of embryos. WIDER IMPLICATIONS OF THE FINDINGS: This is the
      first evidence that developmental incompetence of embryos is an additional
      indication for ionophore treatment. The present approach is exclusively for
      overcoming cleavage arrest. STUDY FUNDING/COMPETING INTERESTS: No funding
      received. T.E. reports fees from Gynemed, outside the submitted work. All co
      authors have no interest to declare.

PMID- 25376462
TI  - Doxycycline alters the expression of inflammatory and immune-related cytokines
      and chemokines in human endometrial cells: implications in irregular uterine
      bleeding.

PMID- 25376464
TI  - Tracing the geographic origin of traded leopard body parts in the indian
      subcontinent with DNA-based assignment tests.
AB  - Illicit trade in wildlife products is rapidly decimating many species across the
      globe. Such trade is often underestimated for wide-ranging species until it is
      too late for the survival of their remaining populations. Policing this trade
      could be vastly improved if one could reliably determine geographic origins of
      illegal wildlife products and identify areas where greater enforcement is needed.
      Using DNA-based assignment tests (i.e., samples are assigned to geographic
      locations), we addressed these factors for leopards (Panthera pardus) on the
      Indian subcontinent. We created geography-specific allele frequencies from a
      genetic reference database of 173 leopards across India to infer geographic
      origins of DNA samples from 40 seized leopard skins. Sensitivity analyses of
      samples of known geographic origins and assignments of seized skins demonstrated
      robust assignments for Indian leopards. We found that confiscated pelts seized in
      small numbers were not necessarily from local leopards. The geographic footprint
      of large seizures appeared to be bigger than the cumulative footprint of several
      smaller seizures, indicating widespread leopard poaching across the subcontinent.
      Our seized samples had male-biased sex ratios, especially the large seizures.
      From multiple seized sample assignments, we identified central India as a
      poaching hotspot for leopards. The techniques we applied can be used to identify
      origins of seized illegal wildlife products and trade routes at the subcontinent
      scale and beyond. 

PMID- 25376463
TI  - PINK1-mediated phosphorylation of Miro inhibits synaptic growth and protects
      dopaminergic neurons in Drosophila.
AB  - Mutations in the mitochondrial Ser/Thr kinase PINK1 cause Parkinson's disease.
      One of the substrates of PINK1 is the outer mitochondrial membrane protein Miro,
      which regulates mitochondrial transport. In this study, we uncovered novel
      physiological functions of PINK1-mediated phosphorylation of Miro, using
      Drosophila as a model. We replaced endogenous Drosophila Miro (DMiro) with
      transgenically expressed wildtype, or mutant DMiro predicted to resist PINK1
      mediated phosphorylation. We found that the expression of phospho-resistant DMiro
      in a DMiro null mutant background phenocopied a subset of phenotypes of PINK1
      null. Specifically, phospho-resistant DMiro increased mitochondrial movement and
      synaptic growth at larval neuromuscular junctions, and decreased the number of
      dopaminergic neurons in adult brains. Therefore, PINK1 may inhibit synaptic
      growth and protect dopaminergic neurons by phosphorylating DMiro. Furthermore,
      muscle degeneration, swollen mitochondria and locomotor defects found in PINK1
      null flies were not observed in phospho-resistant DMiro flies. Thus, our study
      established an in vivo platform to define functional consequences of PINK1
      mediated phosphorylation of its substrates. 

PMID- 25376465
TI  - Intermittent and constant pain and physical function or performance in men and
      women with knee osteoarthritis: data from the osteoarthritis initiative.
AB  - Severe constant and intermittent knee pain are associated with "unacceptable"
      symptoms in older adults with osteoarthritis (OA) [22]. We hypothesized that
      constant and intermittent pain would be independently related to physical
      function, with intermittent knee pain being a better predictor of future declines
      in physical function in early symptomatic knee OA. This study included men (n =
      189) and women (n = 133) with radiographic, unilateral knee OA, observed using
      data from the Osteoarthritis Initiative (OAI). Pain types were measured using the
      Intermittent and Constant Osteoarthritis Pain (ICOAP) scale. Physical function
      was measured using the Western Ontario and McMaster Universities Arthritis Index
      (WOMAC-PF) and Knee Injury and Osteoarthritis Outcome Score (KOOS-FSR) and
      physical performance tests. High baseline intermittent (B = 0.277; p = 0.001) and
      constant (B = 0.252; p = 0.001) knee pain were related to poor WOMAC-PF.
      Increased constant (B = 0.484; p = 0.001) and intermittent (B = 0.104; p = 0.040)
      pain were related to 2-year decreased WOMAC-PF. High baseline intermittent knee
      pain predicted poor KOOS-FSR at year 2 (B = -0.357; p = 0.016). Increased
      constant pain was related to decreased chair stand test performance over 2 years
      in women (B = 0.077; p = 0.001). High baseline intermittent pain was related to
      poor performance on repeated chair stands (B = 0.035; p = 0.021), while baseline
      constant pain was related to poor 400-m walk performance in women (B = 0.636; p =
      0.047). Intermittent and constant knee pain were independent factors in self
      perceived physical function and were important predictors of future limitations
      in physical function. Identifying intermittent and constant pain in early
      symptomatic OA may allow patients to adopt strategies to prevent worsening pain
      and future declines in physical function.

PMID- 25376466
TI  - Screening of latent tuberculosis infection by interferon-gamma release assays in
      rheumatic patients: a systemic review and meta-analysis.
AB  - The aim of this study is to assess the diagnostic value of interferon-gamma
      release assays (IGRAs) for latent tuberculosis infection (LTBI) in patients with
      rheumatic disease before receiving biologic agents. MEDLINE and EMBASE databases
      were used for searching studies concerning the evaluation on the performance of
      IGRAs [QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T
      SPOT.TB] in rheumatic patients before biological therapy. After assessing the
      quality of all studies included in the review, we summarized the results in
      subgroups using forest plots and calculated pooled estimates if applicable. The
      search identified 11 studies with a total sample size of 1940 individuals.
      Compared with the tuberculin skin test (TST), the pooled agreements in QFT-G/GIT
      and T-SPOT.TB were 72 % (95 % confidence interval (CI) 65, 78 %) and 75 % (95 %
      CI 67, 83 %), respectively. BCG vaccination was positively correlated with
      positive rates of TST (pooled odds ratio (OR) 1.64, 95 % CI 1.06, 2.53). Compared
      with TST, IGRAs were better associated with the presentence of one or more
      tuberculosis (TB) risk factors. Neither steroid nor disease-modifying anti
      rheumatic drugs (DMARDs) significantly affect positive IGRA results. In contrast,
      TST positivity was significantly impacted by the use of steroid (pooled OR 0.45,
      95 % CI 0.30, 0.69), but less significantly by the use of DMARDs (pooled OR 0.78,
      95 % CI 0.50, 1.21). In conclusion, in rheumatic patients with previous BCG
      vaccination or currently on steroid therapy, IGRAs would be the better choice to
      identify LTBI by decreasing the false-positivity and false-negativity rate
      compared with conventional TST.

PMID- 25376467
TI  - Rheumatoid arthritis in the Middle East and Africa: are we any closer to
      optimising its management?

PMID- 25376468
TI  - Association of the Smad3 and NFATc2 gene polymorphisms and their serum levels
      with susceptibility to rheumatoid arthritis in Polish cohorts.
AB  - One among many factors involved in induction of rheumatoid arthritis (RA) are T
      cells, the differentiation of which depends upon a unique combination of
      stimulants and subsequent activation of diverse transcription factors. The aim of
      this study was to identify polymorphic variants in Smad3 and NFATc2 genes and
      their possible association with susceptibility to and severity of RA. A total of
      272 RA patients, 321 for Smad3 and 304 for nuclear factor of activated T cells
      (NFAT)c2 healthy individuals, were examined for rs6494629 C/T and rs2289263 T/G
      Smad3 and rs880324 NFATc2 gene polymorphisms using the polymerase chain reaction
      fragment length polymorphism (PCR-RFLP) method and TaqMan single nucleotide
      polymorphism (SNP) genotyping assay, respectively. Serum Smad3 and NFATc2 levels
      in RA patients and controls were measured by enzyme-linked immunosorbent assay
      (ELISA). The rs6494629 C/T Smad3 gene polymorphism under the recessive (TT versus
      CC+CT) and over-dominant (CC+TT versus CT) models were associated with RA
      (P=0.014 and P=0.008, respectively). Smad3 rs2289263 T/G revealed differences in
      the case-control distribution in co-dominant, recessive and over-dominant models
      (P=0.037, P=0.010, P=0.034). Overall, rs6494629 C/T and rs2289263 T/G Smad3 gene
      polymorphisms were in a weak linkage disequilibrium (LD) with D'=0.116 and
      r(2)=0.004. After Bonferroni correction, the genotype-phenotype analysis showed
      no significant correlation of the Smad3 rs6494629 C/T and rs2289263 T/G and
      NFATc2 rs2289263 TT polymorphisms with disease activity, joint damage and extra
      articular manifestation in RA patients. Serum Smad3 and NFATc2 levels were
      significantly higher in RA patients than in control groups (both P=0 0000). The
      present findings indicated that Smad3 genetic polymorphisms may be associated
      with the susceptibility to RA in the Polish population.

PMID- 25376469
TI  - Shiga toxin induces membrane reorganization and formation of long range lipid
      order.
AB  - Lateral variation of the in-plane orientation of lipids in a bilayer is referred
      to as texture. The influence of the protein Shiga toxin on orientational membrane
      texture was studied in phosphatidylcholine lipid bilayers using polarization two
      photon fluorescence microscopy and atomic force microscopy. A content of 1% of
      glycosphingolipid globotriaosylceramide (Gb3) receptor lipids in a bilayer was
      used to bind the Shiga toxin B-subunit to the surface of gel domains. Binding of
      the Shiga toxin B-subunit to lipids led to the modulation of orientational
      membrane texture in gel domains and induced membrane reordering. When Shiga toxin
      was added above the lipid chain melting temperature, the toxin interaction with
      the membrane induced rearrangement and clustering of Gb3 lipids that resulted in
      the long range order and alignment of lipids in gel domains. The toxin induced
      redistribution of Gb3 lipids inside gel domains is governed by the temperature at
      which Shiga toxin was added to the membrane: above or below the phase transition.
      The temperature is thus one of the critical factors controlling lipid
      organization and texture in the presence of Shiga toxin. Lipid chain ordering
      imposed by Shiga toxin binding can be another factor driving the reconstruction
      of lipid organization and crystallization of lipids inside gel domains. 

PMID- 25376470
TI  - Health care quality: a question of supply and demand.

PMID- 25376471
TI  - Cyclin-dependent kinase inhibitor p21 does not impact embryonic endochondral
      ossification in mice.
AB  - Endochondral ossification at the growth plate is regulated by a number of factors
      and hormones. The cyclin-dependent kinase inhibitor p21 has been identified as a
      cell cycle regulator and its expression has been reported to be essential for
      endochondral ossification in vitro. However, to the best of our knowledge, the
      function of p21 in endochondral ossification has not been evaluated in vivo.
      Therefore, the aim of this study was to investigate the function of p21 in
      embryonic endochondral ossification in vivo. Wild-type (WT) and p21 knockout (KO)
      pregnant heterozygous mice were sacrificed on embryonic days E13.5, E15.5 and
      E18.5. Sagittal histological sections of the forearms of the embryos were
      collected and stained with Safranin O and 5-bromo-2'-deoxyuridine (BrdU).
      Additionally, the expression levels of cyclin D1, type II collagen, type X
      collagen, Sox9, and p16 were examined using immunohistochemistry, and the
      expression levels of p27 were examined using immunofluorescence. Safranin O
      staining revealed no structural change between the cartilage tissues of the WT
      and p21KO mice at any time point. Type II collagen was expressed ubiquitously,
      while type X collagen was only expressed in the hypertrophic zone of the
      cartilage tissues. No differences in the levels of Sox9 expression were observed
      between the two groups at any time point. The levels of cyclin D1 expression and
      BrdU uptake were higher in the E13.5 cartilage tissue compared with those
      observed in the embryonic cartilage tissue at subsequent time points. Expression
      of p16 and p27 was ubiquitous throughout the tissue sections. These results
      indicate that p21 may not be essential for embryonic endochondral ossification in
      articular cartilage of mice and that other signaling networks may compensate for
      p21 deletion.

PMID- 25376472
TI  - Stress and resource pathways connecting early socioeconomic adversity to young
      adults' physical health risk.
AB  - Although research has established the impact of early stress, including stressful
      life contexts, and early resources, such as educational attainment, on various
      adolescent health outcomes, previous research has not adequately investigated
      "integrative models" incorporating both stress and resource mediational pathways
      to explain how early socioeconomic adversity impacts physical health outcomes,
      particularly in early life stages. Data on early childhood/adolescent stress and
      socioeconomic resources as well as biomarkers indicating physical health status
      in young adulthood were collected from 11,798 respondents (54 % female) over a 13
      year period from youth participating in the National Study of Adolescent Health
      (Add Health). Physical health risk in young adulthood was measured using a
      composite index of nine regulatory biomarkers of cardiovascular and metabolic
      systems. Heterogeneity in stress and socioeconomic resource pathways was assessed
      using latent class analysis to identify clusters, or classes, of stress and
      socioeconomic resource trajectories. The influence of early socioeconomic
      adversity on young adults' physical health risk, as measured by biomarkers, was
      estimated, and the role of stress and socioeconomic resource trajectory classes
      as linking mechanisms was assessed. There was evidence for the influence of early
      socioeconomic adversity on young adults' physical health risk directly and
      indirectly through stress and socioeconomic resource trajectory classes over the
      early life course. These findings suggest that health models should be broadened
      to incorporate both stress and resource experiences simultaneously. Furthermore,
      these findings have prevention and intervention implications, including the
      importance of early socioeconomic adversity and key intervention points for
      "turning" the trajectories of at-risk youth. 

PMID- 25376473
TI  - Marijuana Use from Middle to High School: Co-occurring Problem Behaviors, Teacher
      Rated Academic Skills and Sixth-Grade Predictors.
AB  - Rising marijuana use and its lowered perceived risk among adolescents highlight
      the importance of examining patterns of marijuana use over time. This study
      identified trajectories of marijuana use among adolescents followed from middle
      through high school, characterized these by co-occurring problem behaviors and
      teacher-rated academic skills (study skills, attention problems, and learning
      problems), and tested sixth-grade predictors of trajectory membership. The sample
      consisted of a randomly-selected cohort of 619 students assessed annually from
      sixth to twelfth grade. Using group-based modeling, we identified four
      trajectories of marijuana use: Abstainer (65.6%), Sporadic (13.9%), Experimental
      (11.5%), and Increasing (9.0%). Compared to Abstainers, students in the Sporadic,
      Experimental and Increasing trajectories reported significantly more co-occurring
      problem behaviors of alcohol use, cigarette smoking, and physical aggression.
      Sporadic and Experimental users reported significantly less smoking and physical
      aggression, but not alcohol use, than Increasing users. Teachers consistently
      rated Abstainers as having better study skills and less attention and learning
      problems than the three marijuana use groups. Compared to Abstainers, the odds of
      dropping out of high school was at least 2.7 times higher for students in the
      marijuana use trajectories. Dropout rates did not vary significantly between
      marijuana use groups. In sixth grade, being male, cigarette smoking, physical
      aggression and attention problems increased the odds of being in the marijuana
      use trajectories. Multiple indicators--student self-reports, teacher ratings and
      high school dropout records--showed that marijuana was not an isolated or benign
      event in the life of adolescents but part of an overall problem behavior
      syndrome.

PMID- 25376474
TI  - Trust but verify.

PMID- 25376475
TI  - Reply to the letter by Leveque et al. entitled 'Psychosurgery for schizophrenia'.

PMID- 25376476
TI  - Effects of gamma-aminobutyric acid on feed intake, growth performance and
      expression of related genes in growing lambs.
AB  - This study was conducted to investigate the effects of rumen-protected gamma
      aminobutyric acid (GABA) on feed intake, growth performance and expression of
      related genes in growing lambs. A total of 24 lambs weaned at age of 50 days were
      divided into four block of six based on their BW, six lambs within a block were
      allocated to three pairs, which were then assigned randomly to three treatments
      with addition of rumen-protected GABA at levels of 0, 70 or 140 mg/day for 6
      weeks. Dry matter intake was recorded weekly in three consecutive days, and BW
      was recorded every two weeks. At the end of the trial, four lambs from each group
      were slaughtered, and duodenum and ileum mucosa were obtained for measurement of
      mRNA abundance of GABA receptor and cholecystokinin receptor. Dry matter intake
      was higher (P<0.01) in the lambs fed 140 mg/day GABA than that in the control or
      70 mg GABA-fed lambs. Average daily gain and nutrients digestibility were not
      different (P>0.05) among treatments. Lambs fed 140 mg/day GABA had higher mRNA
      abundance of GABA-B receptor (P<0.01) and lower mRNA abundance of cholecystokinin
      2 receptor (P<0.01) in duodenum mucosa. Serum CCK content was lower (P<0.01) in
      lambs fed 140 mg/day GABA than that in control. It is indicated that GABA may
      enhance feed intake by regulating GABA- and cholecystokinin-related genes. 

PMID- 25376477
TI  - Discordancy in BRAF mutations among primary and metastatic melanoma lesions:
      clinical implications for targeted therapy.
AB  - Systemic targeted molecular therapy, in the form of a selective BRAF inhibitor
      with or without a MEK inhibitor, is a standard treatment for patients with BRAF
      V600 mutation-positive melanoma with unresectable stage III and IV disease.
      Patients with BRAF mutation-negative primary tumors may manifest BRAF mutation
      positive metastatic disease. It is unclear whether all metastatic lesions carry
      the same BRAF mutation status found in the primary tumor and if discordancy
      exists, in what frequency it occurs. Primary and matched metastatic lesions in 25
      melanoma patients were tested for the BRAF V600E/Ec, V600K, V600D, and V600R
      mutations using a BRAF RGQ PCR kit (Qiagen). Four patients (16%) had
      discrepancies between their primary and metastatic melanoma BRAF status. Of these
      patients, 2 (8%) had BRAF mutation-positive primary melanomas with BRAF mutation
      negative metastatic lesions and 2 (8%) patient had BRAF mutation-negative
      melanoma with a BRAF mutation-positive metastatic lesion. In summary, discordancy
      of BRAF mutation status is not an infrequent finding between primary and
      metastatic melanoma. It may be prudent in previously negative patients to
      determine BRAF mutation status of new metastatic tumors for proper allocation of
      BRAF inhibitor therapy. Discordant BRAF status may have a role in the varying
      patterns of response and inevitable resistance seen with BRAF inhibitor
      therapies. 

PMID- 25376478
TI  - Long-term changes in crash rates after introduction of a Graduated Driver
      Licensing decal provision.
AB  - BACKGROUND: New Jersey (NJ) implemented the first Graduated Driver Licensing
      (GDL) decal provision in the U.S. in May 2010. An initial study reported a 1-year
      post-decal decrease in the crash rate among NJ intermediate drivers aged <21
      years. Longer-term analysis is critical for policymakers in other states
      considering whether to implement a decal provision. PURPOSE: To evaluate the
      longer-term (2-year) effect of NJ's decal provision on overall and age-specific
      crash rates of young drivers with intermediate licenses. METHODS: Monthly per
      driver police-reported crash rates during January 2006-June 2012 were estimated.
      Specific crash types included injury, midnight-4:59am, single-vehicle, multiple
      vehicle, and peer passenger crashes. Negative binomial modeling compared pre-
      versus post-decal crash rates, adjusting for age, gender, calendar month, gas
      price, and 21- to 24-year-old licensed driver crash rates; piecewise negative
      binomial regression models accounted for pre-decal crash trends among
      intermediate drivers. Analyses were conducted in 2013. RESULTS: The adjusted
      crash rate for intermediate drivers was 9.5% lower in the 2-year post-decal
      period than the 4-year pre-decal period (95% CI=0.88, 0.93). Crash rates
      decreased 1.8% per year before the provision and 7.9% per year in the post-decal
      period (p<0.001 for difference in slopes). For several crash types, effects
      appeared to be particularly strong for 18- and 19-year-olds. An estimated 3,197
      intermediate drivers had crashes prevented. CONCLUSIONS: NJ's decal provision was
      associated with a sustained decline in intermediate driver crashes. Future
      research should aim to better understand the causal mechanism by which NJ's decal
      provision may have exerted an effect.

PMID- 25376479
TI  - Life-space mobility and dimensions of depressive symptoms among community
      dwelling older adults.
AB  - OBJECTIVES: To examine the association between life-space mobility and different
      dimensions of depressive symptoms among older community-dwelling people. METHODS:
      Cross-sectional analyses of baseline data of the 'Life-Space Mobility in Old Age'
      cohort study were carried out. The participants were community-dwelling women and
      men aged 75-90 years (N = 848). Data were gathered via structured interviews in
      participants' home. Life-space mobility (the University of Alabama at Birmingham
      (UAB) Life-Space Assessment - questionnaire) and depressive symptoms (Centre for
      Epidemiological Studies Depression Scale, CES-D) were assessed. Other factors
      examined included sociodemographic factors, difficulties walking 500 m, number of
      chronic diseases and the sense of autonomy in participation outdoors (subscale of
      Impact on Participation and Autonomy questionnaire). RESULTS: Poorer life-space
      mobility was associated with higher prevalence of different dimensions of
      depressive symptoms. The associations were partially mediated through walking
      difficulties, health and the sense of autonomy in participation outdoor
      activities. CONCLUSION: Poorer life-space mobility interrelates with higher
      probability for depressive symptoms, thus compromising older adults' mental
      wellbeing. A focus on older adults' life-space mobility may assist early
      identification of persons, who have elevated risk for depressive symptoms. The
      association between life-space mobility and depressive symptoms should be studied
      further utilizing longitudinal study designs to examine temporality and potential
      causality.

PMID- 25376480
TI  - Timing of antimicrobial use influences the evolution of antimicrobial resistance
      during disease epidemics.
AB  - BACKGROUND: Although the emergence and spread of antibiotic resistance have been
      well studied for endemic infections, comparably little is understood for epidemic
      infections such as influenza. The availability of antimicrobial treatments for
      epidemic diseases raises the urgent question of how to deploy treatments to
      achieve maximum benefit despite resistance evolution. Recent simulation studies
      have shown that the number of cases prevented by antimicrobials can be maximized
      by delaying the use of treatments during an epidemic. Those studies focus on
      indirect effects of antimicrobial use: preventing disease among untreated
      individuals. Here, we identify and examine direct effects of antimicrobial use:
      the number of successfully treated cases. METHODOLOGY: We develop mathematical
      models to study how the schedule of antiviral use influences the success or
      failure of subsequent use due to the spread of resistant strains. RESULTS: Direct
      effects are maximized by postponing drug use, even with unlimited stockpiles of
      drugs. This occurs because the early use of antimicrobials disproportionately
      drives emergence and spread of antibiotic resistance, leading to subsequent
      treatment failure. However, for antimicrobials with low effect on transmission,
      the relative benefit of delaying antimicrobial deployment is greatly reduced and
      can only be reaped if the trajectory of the epidemic can be accurately estimated
      early. CONCLUSIONS AND IMPLICATIONS: Health planners face uncertainties during
      epidemics, including the possibility of early containment. Hence, despite the
      optimal deployment time near the epidemic peak, it will often be preferable to
      initiate widespread antimicrobial use as early as possible, particularly if the
      drug is ineffective in reducing transmission.

PMID- 25376481
TI  - Anorexia.

PMID- 25376482
TI  - Severe hyperpigmentation and scarring following glycolic acid peel treatment in
      combination with low-dose isotretinoin.
AB  - BACKGROUND: The application of systemic isotretinoin in the treatment of
      cutaneous photoaging has been well investigated. In addition, well-recognized
      topical antiaging therapies such as superficial chemical peeling (CP) with alpha
      hydroxy acids have been shown to be more helpful when combined with low-dose oral
      isotretinoin. Even though the combination of systemic isotretinoin and medium to
      deep CP has been associated with serious side effects such as delayed wound
      healing and enlarged incidence of scarring, to date superficial CP and
      concomitant systemic isotretinoin have been considered safe. CASE PRESENTATION:
      In this report, we present the case of a patient receiving low-dose oral
      isotretinoin therapy who developed severe painful erythema and erosions that led
      to permanent hyperpigmentation and scarring of her face and neck after undergoing
      superficial CP with glycolic acid. CONCLUSIONS: There is a potential risk of
      hyperpigmentation and scarring with the use of a combination of low-dose oral
      isotretinoin and glycolic acid peeling.

PMID- 25376483
TI  - Green and sensitive supercritical fluid chromatographic-tandem mass spectrometric
      method for the separation and determination of flutriafol enantiomers in
      vegetables, fruits, and soil.
AB  - A green and sensitive chiral analytical method was developed to determine
      flutriafol enantiomers in vegetables (tomato, cucumber), fruits (apple, grape),
      and soil by supercritical fluid chromatography-tandem mass spectrometry. The
      enantioseparation was performed within 3.50 min using Chiralpak IA-3 column with
      CO2/methanol (88:12, v/v) as the mobile phase at a 2.2 mL/min flow rate. The
      postcolumn compensation technology provided with 1% formic acid/methanol greatly
      improved the ionization efficiency of mass spectrometry. Column temperature, auto
      back pressure regulator pressure, and flow rate of compensation solvent were
      optimized to 30  degrees C, 2200 psi, and 0.1 mL/min, respectively. The simple
      and fast QuEChERS pretreatment method was adopted. Mean recoveries for flutriafol
      enantiomers were 77.2-98.9% with RSDs <= 9.6% in all matrices. The limits of
      quantification ranged from 0.41 to 1.18 MUg/kg. Well-applied to analyze authentic
      samples, the developed method could act as a versatile strategy for the analysis
      of flutriafol enantiomers in food and environmental matrices. 

PMID- 25376484
TI  - Repeat polymorphisms in ESR2 and AR and colorectal cancer risk and prognosis:
      results from a German population-based case-control study.
AB  - BACKGROUND: Evidence has accumulated which suggests that sex steroids influence
      colorectal cancer development and progression. We therefore assessed the
      association of repeat polymorphisms in the estrogen receptor beta gene (ESR2) and
      the androgen receptor gene (AR) with colorectal cancer risk and prognosis.
      METHODS: The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases
      (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for
      sex, age and county of residence. Colorectal cancer risk associations overall and
      specific for gender were evaluated using multivariate logistic regression models
      adjusted for sex, county of residence and age. Associations with overall and
      disease-specific survival were evaluated using Cox proportional hazard models
      adjusted for established prognostic factors (diagnosis of other cancer after
      colorectal cancer diagnosis, detection by screening, treatment with adjuvant
      chemotherapy, tumour extent, nodal status, distant metastasis, body mass index,
      age at diagnosis and year of diagnosis) and stratified for grade of
      differentiation. Heterogeneity in gender specific associations was assessed by
      comparing models with and without a multiplicative interaction term by means of a
      likelihood ratio test. RESULTS: The average number of ESR2 CA repeats was
      associated with a small 5% increase in colorectal cancer risk (OR = 1.05, 95% CI
      1.01-1.10) without significant heterogeneity according to gender or tumoural ESR2
      expression. We found no indication for an association between the AR CAG repeat
      polymorphisms and risk of colorectal cancer. The ESR2 CA and AR CAG repeat
      polymorphisms were not associated with overall survival or disease specific
      survival after colorectal cancer diagnosis. CONCLUSIONS: Higher numbers of ESR2
      CA repeats are potentially associated with a small increase in colorectal cancer
      risk. Our study does not support an association between colorectal cancer
      prognosis and the investigated repeat polymorphisms.

PMID- 25376485
TI  - The prevalence and determinants of catastrophic health expenditures attributable
      to non-communicable diseases in low- and middle-income countries: a
      methodological commentary.
AB  - BACKGROUND: Non-communicable diseases (NCDs), while traditionally considered a
      "rich world"-problem, have been spreading fast in low and middle income countries
      and by now account for a large share of mortality and ill-health in these
      countries, too. In addition to the disease burden, NCDs may also impose a
      substantial economic cost. One way in which NCDs might impact people's economic
      well-being may be via the out-of-pocket expenditures required to cover treatment
      and other costs associated with suffering from an NCD. METHODS: In this
      commentary, we identify and discuss the methodological challenges related to
      cross-country comparison of-out-of-pocket and catastrophic out-of-pocket health
      care expenditures, attributable to NCDs, focussing on low and middle income
      countries. RESULTS: There is significant evidence of substantial cost burden
      placed by NCDs on patients living in low and middle income countries, with most
      of it being heavily concentrated among low socioeconomic status groups. However,
      a large variation in definition of COOPE between studies prevents cross-country
      comparison. In addition, as most studies tend to be observational, causal
      inferences are often not possible. This is further complicated by the cross
      sectional nature of studies, small sample sizes, and/or limited duration of
      follow-up of patients. Most evidence for certain conditions (e.g., cancer) tends
      to be collected in high-income countries only. CONCLUSIONS: The definitions for
      COOPEs should be standardized as much as possible, to enable comparison of COOPE
      prevalence between countries. Prospective study design using larger samples
      representative of broader sections of local population, collecting better data on
      both direct and indirect treatment costs is also needed.

PMID- 25376486
TI  - Endoscopic ultrasonography for tumor node staging and vascular invasion in
      pancreatic cancer: a meta-analysis.
AB  - BACKGROUND/AIMS: The accurate staging of pancreatic cancer (PanCa) is crucial in
      the development of a stage-specific treatment plan for PanCa patients. We aimed
      to perform a meta-analysis of endoscopic ultrasonography (EUS) in the tumor node
      (TN) staging and evaluation of vascular invasion in PanCa. METHODS: A meta
      analysis of diagnostic accuracy parameters was performed to evaluate the EUS
      based TN staging, and vascular invasion by PanCa was compared to the results of
      intraoperative staging or to the histopathology of resected specimens. RESULTS:
      Twenty studies with 726 PanCa cases were identified from 281 articles. The pooled
      sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood
      ratio (NLR), and diagnostic odds ratio (DOR) were 0.72, 0.90, 6.27, 0.28, and
      24.69, respectively, for T1-2 staging and 0.90, 0.72, 3.58, 0.16, and 24.69,
      respectively, for T3-4 staging. The overall sensitivity, specificity, PLR, NLR,
      and DOR were 0.62, 0.74, 2.54, 0.51, and 6.67, respectively, for N staging
      (positive vs. negative) and 0.87, 0.92, 7.16, 0.20, and 56.19, respectively, for
      vascular invasion. The area under the curve was 0.90, 0.90, 0.79, and 0.94 for T1
      2 staging, T3-4 staging, N staging, and vascular invasion, respectively.
      CONCLUSIONS: EUS is a reliable and accurate diagnostic tool for the TN staging
      and evaluation of vascular invasion in PanCa. The nodal staging accuracy using
      EUS is less satisfactory.

PMID- 25376487
TI  - The use of bisphosphonates in pediatrics.
AB  - Bisphosphonates are widely used for the prevention and treatment of osteoporosis
      in adulthood. In the last years, bisphosphonates have been increasingly used in
      pediatric patients for the treatment of a growing number of disorders associated
      with osteoporosis, resistant hypercalcemia or heterotopic calcifications. The use
      of bisphosphonates in pediatric patients has been proven safe; however, the risk
      of potential severe consequences into adulthood should be kept in mind. Well
      defined criteria for bisphosphonates treatment in pediatric patients are not
      specified, therefore an accurate selection of patients who could benefit from
      bisphosphonates is mandatory. A strict follow-up of pediatric patients receiving
      long-term bisphosphonate therapy is strongly recommended. The purpose of this
      mini review is to provide a summary of current knowledge on some main general
      aspects of the structure, mechanisms of action, pharmacokinetics, and
      bioavailability of bisphosphonates, and to focus on the latest advances of
      bisphosphonate treatment in pediatric patients. Particular attention has been
      paid to the common and potential adverse effects of bisphosphonate treatment, and
      some suggestions concerning the clinical approach and general measures for
      bisphosphonate treatment in pediatric patients are reported.

PMID- 25376488
TI  - Lipidomics applications for discovering biomarkers of diseases in clinical
      chemistry.
AB  - Lipids are the fundamental components of biological membranes as well as the
      metabolites of organisms. Lipids play diverse and important roles in biologicals.
      The lipid imbalance is closely associated with numerous human lifestyle-related
      diseases, such as atherosclerosis, obesity, diabetes, and Alzheimer's disease.
      Lipidomics or lipid profiling is a system-based study of all lipids aiming at
      comprehensive analysis of lipids in the biological system. Lipidomics has been
      accepted as a lipid-related research tool in lipid biochemistry, clinical
      biomarker discovery, disease diagnosis, and in understanding disease pathology.
      Lipidomics will not only provide insights into the specific functions of lipid
      species in health and disease, but will also identify potential biomarkers for
      establishing preventive or therapeutic programs for human diseases. This review
      presents an overview of lipidomics followed by in-depth discussion of its
      application to the study of human diseases, including extraction methods of
      lipids, analytical technologies, data analysis, and clinical research in cancer,
      neuropsychiatric disease, cardiovascular disease, kidney disease, and respiratory
      disease. We describe the current status of the identification of metabolic
      biomarkers in different diseases. We also discuss the lipidomics for the future
      perspectives and their potential problems. The application of lipidomics in
      clinical studies may provide new insights into lipid profiling and
      pathophysiological mechanisms. 

PMID- 25376489
TI  - Enzymatically synthesized inorganic polymers as morphogenetically active bone
      scaffolds: application in regenerative medicine.
AB  - In recent years a paradigm shift in understanding of human bone formation has
      occurred that starts to change current concepts in tissue engineering of bone and
      cartilage. New discoveries revealed that fundamental steps in biomineralization
      are enzyme driven, not only during hydroxyapatite deposition, but also during
      initial bioseed formation, involving the transient deposition and subsequent
      transformation of calcium carbonate to calcium phosphate mineral. The principal
      enzymes mediating these reactions, carbonic anhydrase and alkaline phosphatase,
      open novel targets for pharmacological intervention of bone diseases like
      osteoporosis, by applying compounds acting as potential activators of these
      enzymes. It is expected that these new findings will give an innovation boost for
      the development of scaffolds for bone repair and reconstruction, which began with
      the use of bioinert materials, followed by bioactive materials and now leading to
      functional regenerative tissue units. These new developments have become possible
      with the discovery of the morphogenic activity of bioinorganic polymers,
      biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic,
      enzymatic mechanism, a driving force along with the development of novel rapid
      prototyping three-dimensional (3D) printing methods and bioprinting (3D cell
      printing) techniques that may allow a fabrication of customized implants for
      patients suffering in bone diseases in the future. 

PMID- 25376490
TI  - New insights into the mechanism for VACM-1/cul5 expression in vascular tissue in
      vivo.
AB  - Vasopressin-activated calcium-mobilizing (VACM-1)/cul5 is the least conserved
      member of a cullin protein family involved in the formation of E3-specific ligase
      complexes that are responsible for delivering the ubiquitin protein to their
      target substrate proteins selected for ubiquitin-dependent degradation. This
      chapter summarizes work to date that has focused on VACM-1/cul5's tissue-specific
      expression in vivo and on its potential role in the control of specific cellular
      signaling pathways in those structures. As mammalian cells may contain hundreds
      of E3 ligases, identification VACM-1/cul5 as a specific subunit of the system
      that is expressed in the endothelium and in collecting tubules, structures known
      for their control of cellular permeability, may have significant implications
      when designing studies to elucidate the mechanism of water conservation. For
      example, VACM-1/cul5 expression is affected by water deprivation in some tissues
      and there is a potential relationship between neddylated VACM-1/cul5 and
      aquaporins. 

PMID- 25376492
TI  - Cell and molecular biology of epidermal growth factor receptor.
AB  - The epidermal growth factor receptor (EGFR) has been one of the most intensely
      studied cell surface receptors due to its well-established roles in developmental
      biology, tissue homeostasis, and cancer biology. The EGFR has been critical for
      creating paradigms for numerous aspects of cell biology, such as ligand binding,
      signal transduction, and membrane trafficking. Despite this history of discovery,
      there is a continual stream of evidence that only the surface has been scratched.
      New ways of receptor regulation continue to be identified, each of which is a
      potential molecular target for manipulating EGFR signaling and the resultant
      changes in cell and tissue biology. This chapter is an update on EGFR-mediated
      signaling, and describes some recent developments in the regulation of receptor
      biology. 

PMID- 25376491
TI  - The UNC-45 myosin chaperone: from worms to flies to vertebrates.
AB  - UNC-45 (uncoordinated mutant number 45) is a UCS (UNC-45, CRO1, She4p) domain
      protein that is critical for myosin stability and function. It likely aides in
      folding myosin during cellular differentiation and maintenance, and protects
      myosin from denaturation during stress. Invertebrates have a single unc-45 gene
      that is expressed in both muscle and nonmuscle tissues. Vertebrates possess one
      gene expressed in striated muscle (unc-45b) and another that is more generally
      expressed (unc-45a). Structurally, UNC-45 is composed of a series of alpha
      helices connected by loops. It has an N-terminal tetratricopeptide repeat domain
      that binds to Hsp90 and a central domain composed of armadillo repeats. Its C
      terminal UCS domain, which is also comprised of helical armadillo repeats,
      interacts with myosin. In this chapter, we present biochemical, structural, and
      genetic analyses of UNC-45 in Caenorhabditis elegans, Drosophila melanogaster,
      and various vertebrates. Further, we provide insights into UNC-45 functions, its
      potential mechanism of action, and its roles in human disease. 

PMID- 25376493
TI  - Centrosomes and the art of mitotic spindle maintenance.
AB  - The assembly of a bipolar spindle lies at the heart of mitotic chromosome
      segregation. In animal somatic cells, the process of spindle assembly involves
      multiple complex interactions between various cellular compartments, including an
      emerging antiparallel microtubule network, microtubule-associated motor proteins
      and spindle assembly factors, the cell's cortex, and the chromosomes themselves.
      The result is a dynamic structure capable of aligning pairs of sister chromatids,
      sensing chromosome misalignment, and generating force to segregate the replicated
      genome into two daughters. Because the centrosome lies at the center of the array
      of microtubule minus-ends, and the essential one-to-two duplication of the
      centrosome prior to mitosis is linked to cell cycle progression, this organelle
      has long been implicated as a device to generate spindle bipolarity. However,
      this classic model for spindle assembly is challenged by observations and
      experimental manipulations demonstrating that acentrosomal cells can and do form
      bipolar spindles, both mitotic and meiotic. Indeed, recent comprehensive
      proteomic analysis of centrosome-dependent versus independent mitotic spindle
      assembly mechanisms reveals a large, common set of genes required for both
      processes, with very few genes needed to differentiate between the two. While
      these studies cast doubt on an absolute role for the centrosome in establishing
      spindle polarity, it is clear that having too few or too many centrosomes results
      in abnormal chromosome segregation and aneuploidy. Here we review the case both
      for and against the role of the centrioles and centrosomes in ensuring proper
      assembly of a bipolar spindle, an essential element in the maintenance of genomic
      stability. 

PMID- 25376494
TI  - Dual roles of orphan nuclear receptor TR3/Nur77/NGFI-B in mediating cell survival
      and apoptosis.
AB  - As a transcriptional factor, Nur77 has sparked interests across different
      research fields in recent years. A number of studies have demonstrated the
      functional complexity of Nur77 in mediating survival/apoptosis in a variety of
      cells, including tumor cells. Conflicting observations also exist in clinical
      reports, in that TR3 behaves like an oncogene in tumors of the GI tract, lung,
      and breast, that is negatively associated with tumor stage and patient prognosis;
      while functions as a tumor suppressor gene in malignancies of the hematological
      and lymphatic system, skin, and ovary whose malfunction results in
      carcinogenesis. This chapter summarizes the apparent opposing effects of Nur77 on
      cells and explicates the mechanisms that determine the functional preference of
      Nur77. We conclude that in addition to cell type and agent context, other factors
      such as cellular localization, signaling pathway, and posttranslational
      modification also determine the final effects of Nur77 on cells. 

PMID- 25376495
TI  - Bioinspired peptide nanostructures for organic field-effect transistors.
AB  - Peptide-based nanostructures derived from natural amino acids are superior
      building blocks for biocompatible devices as they can be used in a bottom-up
      process without the need for expensive lithography. A dense nanostructured
      network of l,l-diphenylalanine (FF) was synthesized using the solid-vapor-phase
      technique. Formation of the nanostructures and structure-phase relationship were
      investigated by electron microscopy and Raman scattering. Thin films of l,l
      diphenylalanine micro/nanostructures (FF-MNSs) were used as the dielectric layer
      in pentacene-based field-effect transistors (FETs) and metal-insulator
      semiconductor diodes both in bottom-gate and in top-gate structures. Bias stress
      studies show that FF-MNS-based pentacene FETs are more resistant to degradation
      than pentacene FETs using FF thin film (without any nanostructures) as the
      dielectric layer when both are subjected to sustained electric fields.
      Furthermore, it is demonstrated that the FF-MNSs can be functionalized for
      detection of enzyme-analyte interactions. This work opens up a novel and facile
      route toward scalable organic electronics using peptide nanostructures as
      scaffolding and as a platform for biosensing. 

PMID- 25376496
TI  - A click-and-release approach to CO prodrugs.
AB  - Carbon monoxide belongs to the family of signaling molecules and has been shown
      to possess therapeutic effects. Similar to NO, safe delivery of CO is a key issue
      in developing CO-based therapeutics. Herein we report a "click and release" CO
      prodrug approach, which allows the release of CO under physiological conditions
      without the need for light irradiation. The system releases CO in a triggered and
      controllable manner and possesses the potential of tunable release rates. 

PMID- 25376497
TI  - Naturalism about health and disease: adding nuance for progress.
AB  - The literature on health and diseases is usually presented as an opposition
      between naturalism and normativism. This article argues that such a picture is
      too simplistic: there is not one opposition between naturalism and normativism,
      but many. I distinguish four different domains where naturalist and normativist
      claims can be contrasted: (1) ordinary usage, (2) conceptually clean versions of
      "health" and "disease," (3) the operationalization of dysfunction, and (4) the
      justification for that operationalization. In the process I present new arguments
      in response to Schwartz (2007) and Hausman (2012) and expose a link between the
      arguments made by Schwartz (2007) and Kingma (2010). Distinguishing naturalist
      claims at these four domains will allow us to make progress by (1) providing more
      nuanced, intermediate positions about a possible role for values in health and
      disease; and (2) assisting in the addressing of relativistic worries about the
      value-ladenness of health and disease.

PMID- 25376498
TI  - Reframing the disease debate and defending the biostatistical theory.
AB  - Similarly to other accounts of disease, Christopher Boorse's Biostatistical
      Theory (BST) is generally presented and considered as conceptual analysis, that
      is, as making claims about the meaning of currently used concepts. But conceptual
      analysis has been convincingly critiqued as relying on problematic assumptions
      about the existence, meaning, and use of concepts. Because of these problems,
      accounts of disease and health should be evaluated not as claims about current
      meaning, I argue, but instead as proposals about how to define and use these
      terms in the future, a methodology suggested by Quine and Carnap. I begin this
      article by describing problems with conceptual analysis and advantages of
      "philosophical explication," my favored approach. I then describe two attacks on
      the BST that also question the entire project of defining "disease." Finally, I
      defend the BST as a philosophical explication by showing how it could define
      useful terms for medical science and ethics. 

PMID- 25376499
TI  - The solution chemistry and reactivity of lacunary Keggin silicotungstates
      monitored in real-time by a combination of mass spectrometry and
      electrochemistry.
AB  - The solution chemistry of a series of mono-, di- and trilacunary Keggin
      silicotungstates was investigated by electrospray ionization mass spectrometry
      (ESI-MS) and general electrospray features especially for lacunary POMs are
      summarized. The reactions of vanadium incorporation into the lacunary structures
      were successfully monitored in real-time by a combination of ESI-MS and
      differential pulse voltammetry (DPV). It was found that all the reactions took
      place instantaneously and that a subtle speciation change occurred at prolonged
      reaction times for the pair of reactants, monovacant silicotungstate and sodium
      metavanadate, suggesting a conversion of mono- to divanadium substituted
      derivatives. This was shown to result from a solution process, not an ESI-induced
      reaction, by DPV measurements. The relative stabilities of the V-substituted
      products were assessed in both solution and gas phases. 

PMID- 25376500
TI  - Immunization of mice with Plasmodium TCTP delays establishment of Plasmodium
      infection.
AB  - Translationally controlled tumour protein (TCTP) may play an important role in
      the establishment or maintenance of parasitemia in a malarial infection. In this
      study, the potential of TCTP as a malaria vaccine was investigated in two trials.
      In the initial vaccine trial, Plasmodium falciparum TCTP (PfTCTP) was expressed
      in Saccharomyces cerevisiae and used to immunize BALB/c mice. Following challenge
      with Plasmodium yoelii YM, parasitemia was significantly reduced during the early
      stages of infection. In the second vaccine trial, the TCTP from P. yoelii and P.
      berghei was expressed in Escherichia coli and used in several mouse malaria
      models. A significant reduction in parasitemia in the early stages of infection
      was observed in BALB/c mice challenged with P. yoelii YM. A significantly reduced
      parasitemia at each day leading up to a delayed and reduced peak parasitemia was
      also observed in BALB/c mice challenged with the nonlethal Plasmodium chabaudi
      (P.c.) chabaudi AS. These results suggest that TCTP has an important role for
      parasite establishment and may be important for pathogenesis. 

PMID- 25376501
TI  - Aggregation-Induced Emission Rotors: Rational Design and Tunable Stimuli
      Response.
AB  - A novel molecular design strategy is provided to rationally tune the stimuli
      response of luminescent materials with aggregation-induced emission (AIE)
      characteristics. A series of new AIE-active molecules (AIE rotors) are prepared
      by covalently linking different numbers of tetraphenylethene moieties together.
      Upon gradually increasing the number of rotatable phenyl rings, the sensitivity
      of the response of the AIE rotors to viscosity and temperature is significantly
      enhanced. Although the molecular size is further enlarged, the performance is
      only slightly improved due to slightly increased effective rotors, but with
      largely increased rotational barriers. Such molecular engineering and
      experimental results offer more in-depth insight into the AIE mechanism, namely,
      restriction of intramolecular rotations. Notably, through this rational design,
      the AIE rotor with the largest molecular size turns out to be the most
      viscosensitive luminogen with a viscosity factor of up to 0.98.

PMID- 25376502
TI  - Physical assembly of Ag nanocrystals on enclosed surfaces in monocrystalline Si.
AB  - Growth of thin crystals on external substrate surfaces by many different methods
      is a well-known technique, but its extension to inner, enclosed surfaces of large
      defects in monocrystalline materials has not yet been reported. The literature on
      thin film growth and defects in materials can be leveraged to fabricate new
      structures for a variety of applications. Here we show a physical process of
      nucleation and evolution of nanocrystalline silver inside voids in
      monocrystalline silicon. We found that the Ag growth is hetero-epitaxial using a
      coincident site lattice. Alignment of Ag and Si atomic planes is uniformly
      observed by high resolution transmission electron microscopy and macroscopically
      by channeling Rutherford backscattering spectrometry. 

PMID- 25376503
TI  - Investigation into sources of contamination of cattle with phenylbutazone.

PMID- 25376504
TI  - Horse impoundments under Control of Horses legislation in the Munster region of
      Ireland: factors affecting euthanasia.
AB  - Recently, considerable international attention has been paid to the problem of
      unwanted horses. In Ireland, stray horses, particularly in urban areas, are a
      further problem. The Control of Horses Act 1996 was enacted in response to an
      ongoing problem of uncontrolled horses in public places. As yet, no research work
      has been conducted focusing on stray horses in Ireland. This paper describes
      horses impounded under the Act in the Munster region of Ireland during 2005-2012
      and the factors influencing decisions regarding their disposal. A logistic
      regression model was developed to investigate factors influencing the probability
      that a horse was euthanised during impoundment. In total, 3625 seizure events
      were recorded, most towards the end of the study period. Predictors for
      euthanasia during 2010-2012 included seizure location, sex, age, colour, body
      condition score and year. This study highlights the problem of stray horses in
      Ireland, particularly in urban areas. There is a need for rigorous enforcement of
      newly enacted horse identification legislation, allowing a fully integrated
      traceability system. More is required to manage the long-established societal
      problems of stray horses in urban settings, with a uniform approach by all Local
      Authorities being long overdue.

PMID- 25376505
TI  - Increasing antimicrobial resistance in clinical isolates of Staphylococcus
      intermedius group bacteria and emergence of MRSP in the UK.
AB  - Frequencies of antimicrobial resistance were determined amongst 14,555 clinical
      Staphylococcus intermedius group (SIG) isolates from UK dogs and cats to estimate
      resistance trends and quantify the occurrence of meticillin-resistant
      Staphylococcus pseudintermedius (MRSP). Reports from two diagnostic laboratories
      (13,313 general submissions, 1242 referral centre only submissions) were analysed
      retrospectively (2003/2006-2012). MRSP were defined by phenotypic resistance to
      meticillin and concurrent broad beta-lactam resistance; a subset was confirmed
      genetically (SIG-specific nuc and mecA). Trends were analysed by Cochran-Armitage
      test. Resistance remained below 10 per cent for cefalexin, amoxicillin-clavulanic
      acid and the fluoroquinolones. Increasing resistance trends were seen in both
      laboratories for ampicillin/amoxicillin (both P<0.001), cefovecin (both P<0.046)
      and enrofloxacin (both P<0.02). Resistance to cefalexin increased over time in
      referral hospital isolates (P<0.001) to clindamycin (P=0.01) and trimethoprim
      sulfamethoxazole (P=0.001) amongst general laboratory submissions. Overall, 106
      MRSP were isolated (0.7 per cent of submissions) including 32 (2.6 per cent of
      submissions, all genetically confirmed) from the referral centre population
      (inter-laboratory difference P<0.001). Against a background of widely susceptible
      SIG isolates, a new trend of increasing resistance to important antimicrobials
      was identified overtime and the emergence of MRSP from UK clinical cases was
      confirmed. Attention to responsible use of antibacterial therapy in small animal
      practice is urgently needed. 

PMID- 25376507
TI  - Impact of pore connectivity on the design of long-lived zeolite catalysts.
AB  - Without techniques sensitive to complex pore architectures, synthetic efforts to
      enhance molecular transport in zeolite and other porous materials through
      hierarchical structuring lack descriptors for their rational design. The power of
      positron annihilation lifetime spectroscopy (PALS) to characterize the pore
      connectivity in hierarchical MFI zeolites is demonstrated, establishing a direct
      link with the enhanced catalyst lifetime in the conversion of methanol to
      valuable hydrocarbons. The unique ability to capture subtleties of the
      hierarchical structure originates from the dynamic nature of the ortho
      positronium response to the pore network. The findings reveal the strong
      dependence on the way in which the hierarchical zeolites are manufactured, having
      direct implications for the practical realization of these advanced catalysts. 

PMID- 25376506
TI  - Magnetic hydroxyapatite nanoparticles: an efficient adsorbent for the separation
      and removal of nitrate and nitrite ions from environmental samples.
AB  - A novel type of magnetic nanosorbent, hydroxyapatite-coated Fe2O3 nanoparticles
      was synthesized and used for the adsorption and removal of nitrite and nitrate
      ions from environmental samples. The properties of synthesized magnetic
      nanoparticles were characterized by scanning electron microscopy, Fourier
      transform infrared spectroscopy, and X-ray powder diffraction. After the
      adsorption process, the separation of gamma-Fe2O3@hydroxyapatite nanoparticles
      from the aqueous solution was simply achieved by applying an external magnetic
      field. The effects of different variables on the adsorption efficiency were
      studied simultaneously using an experimental design. The variables of interest
      were amount of magnetic hydroxyapatite nanoparticles, sample volume, pH, stirring
      rate, adsorption time, and temperature. The experimental parameters were
      optimized using a Box-Behnken design and response surface methodology after a
      Plackett-Burman screening design. Under the optimum conditions, the adsorption
      efficiencies of magnetic hydroxyapatite nanoparticles adsorbents toward NO3(-)
      and NO2(-) ions (100 mg/L) were in the range of 93-101%. The results revealed
      that the magnetic hydroxyapatite nanoparticles adsorbent could be used as a
      simple, efficient, and cost-effective material for the removal of nitrate and
      nitrite ions from environmental water and soil samples.

PMID- 25376508
TI  - Intrahepatic fat content correlates with soluble CD163 in relation to weight loss
      induced by Roux-en-Y gastric bypass.
AB  - OBJECTIVE: Soluble CD163 (sCD163) is a new marker of obesity-related metabolic
      complications. sCD163 and CD163 mRNA were investigated in relation to the fat
      distribution at baseline and 12 months after Roux-en-Y gastric bypass (RYGB).
      METHODS: Thirty-one obese subjects (BMI: 42.3 +/- 4.7 kg/m(2)) were enrolled.
      Subcutaneous (SAT) and visceral adipose tissue (VAT) volume were determined by
      MRI, intrahepatic lipid content (IHL) by MR-spectroscopy, and body composition by
      DXA. Fasting blood samples and adipose tissue samples were obtained, and ELISA
      and RT-PCR were performed. RESULTS: RYGB-induced weight loss (36 +/- 11 kg) was
      accompanied by a significant reduction in sCD163 (2.1 +/- 0.8 mg/l vs. 1.7 +/-
      0.7 mg/l), SAT, VAT, and IHL (all, P < 0.001). At baseline, sCD163 was associated
      with VAT (r = 0.40, P < 0.05) but not with SAT or IHL. Moreover, CD163 mRNA was
      significantly upregulated in VAT compared with SAT at baseline (P < 0.05) and
      significantly downregulated in SAT after RYGB (P < 0.001). DeltasCD163 was
      significantly associated with DeltaIHL after RYGB compared with baseline (r =
      0.40, P < 0.05). CONCLUSIONS: RYGB-induced weight loss results in a reduction of
      sCD163 and CD163 mRNA. The association between DeltasCD163 and DeltaIHL may
      reflect a reduction in sCD163-producing Kupffer cells in the liver. Moreover,
      sCD163 may be a marker of "unhealthy" fat distribution in obese subjects.

PMID- 25376509
TI  - Phosphorescent light-emitting transistors: harvesting triplet excitons.
AB  - Phosphorescent light-emitting transistors, in which light emission from singlet
      and triplet energy levels is harvested using solution-processed materials, are
      presented. While a green phosphorescent dendrimer exhibits an external quantum
      efficiency of 0.45% at 480 cd m(-2) , a red polymer/phosphorescent small-molecule
      blend produces a brightness exceeding 30 cd m(-2) with a relatively high hole
      mobility of 2.5 * 10(-2)  cm(2) V(-1) s(-1) . 

PMID- 25376510
TI  - Natural stressors in uncontaminated sediments of shallow freshwaters: the
      prevalence of sulfide, ammonia, and reduced iron.
AB  - Potentially toxic levels of 3 naturally occurring chemical stressors (dissolved
      sulfide, ammonia, and iron) can appear in freshwater sediments, although their
      roles in shaping ecosystem structure (i.e., plant and animal communities) and
      function (e.g., biologically mediated elemental cycles) have received little
      study. The present critical review discusses the prevalence and ecological
      effects of potentially toxic concentrations of sulfide, ammonia, and iron in
      uncontaminated freshwater sediments, including a review of the literature as well
      as a case study presenting previously unpublished data on sediment porewaters
      from a diverse set of shallow (<2 m) freshwater ecosystems in southwest Michigan,
      USA. Measured concentrations are compared with surface water quality criteria
      established by the US Environmental Protection Agency (USEPA) and with acute and
      chronic toxic thresholds in the published literature, where available. Based on
      USEPA criteria for aquatic life for these 3 stressors, the benthic environment of
      almost every freshwater ecosystem sampled was theoretically stressful to some
      component of aquatic life in some area or at some time (i.e., in at least 1
      sample), and 54% of samples exceeded more than 1 criterion simultaneously.
      Organismal tolerances to chemical stressors vary, so the observed concentrations
      are likely shaping benthic animal communities and influencing rates of ecosystem
      processes. Consideration of the role of natural chemical stressors is important
      in shaping freshwater benthic environments and in developing bioassessments,
      restoration goals, and remediation plans. Environ Toxicol Chem 2015;34:467-479.
      (c) 2014 SETAC. 

PMID- 25376511
TI  - Visualization of the eustachian tube lumen with Valsalva computed tomography.
AB  - OBJECTIVES/HYPOTHESIS: Assess the feasibility of using the Valsalva maneuver to
      visualize the cartilaginous eustachian tube lumen with computed tomography (CT)
      in subjects with no ear disease. STUDY DESIGN: Prospective case series study.
      METHODS: Thirty-eight consecutive patients undergoing CT of the sinuses for nose
      related complaints with normal radiographic findings consented for a CT of the
      temporal bone while performing the Valsalva maneuver. Multiplanar reconstruction
      was performed along the axis of the tube. Images were assessed for visualization
      of the whole length of lumen of the tube, or partial visualization with ratio of
      visualized to nonvisualized segments. RESULTS: The Valsalva maneuver allowed
      visualization of the whole length of the tube in 27/76 (35%) ears examined. It
      consistently visualized the distal one-third of the cartilaginous tube in 71/76
      (94%) ears. Paradoxical collapse of the eustachian tube was present in three ears
      along with evidence of poor Valsalva technique. CONCLUSIONS: Valsalva CT
      consistently allows visualization of the lumen of the distal one-third of the
      eustachian tube in a majority of patients with no eustachian tube-related
      complaints. This technique might be helpful in localizing eustachian tube
      pathology in patients with obstructive tube symptoms.

PMID- 25376512
TI  - Impact of pretreatment interstitial lung disease on radiation pneumonitis and
      survival after stereotactic body radiation therapy for lung cancer.
AB  - INTRODUCTION: To investigate the impact of pre-existing radiological interstitial
      lung disease (ILD) findings on the incidence of radiation pneumonitis (RP) and
      clinical outcomes after stereotactic body radiation therapy (SBRT) for stage I
      non-small-cell lung cancer. METHODS: We included 157 consecutive patients who
      underwent SBRT alone for stage I non-small-cell lung cancer and whose
      pretreatment lung computed tomography images were available for retrospective
      review. The pretreatment computed tomography images were evaluated
      retrospectively for the presence of ILD. The incidence of RP, overall survival
      (OS) rate, and the incidence of disease progression and local progression were
      evaluated between patients with ILD (ILD[+]) and without ILD (ILD[-]). RESULTS:
      Pre-existing ILD was identified in 20 patients. The median follow-up period was
      39.5 months. The incidences of RP worse than grade 2 (>= Gr2 RP) and worse than
      grade 3 (>= Gr3 RP) were significantly higher in ILD(+) than ILD(-) (1 year >=
      Gr2 RP rate, 55.0% versus 13.3%; p < 0.001 and 1year >= Gr3 RP rate 10.0% versus
      1.5%; p = 0.020). Multivariate analysis also indicated that ILD(+) was a risk
      factor for >= Gr2 and >= Gr3 RP, and the volume of the irradiated lung. The OS
      rate tended to be worse in ILD(+) than ILD(-) (3-year OS, 53.8% versus 70.8%; p =
      0.28). No difference was observed in the disease progression or local progression
      rates. CONCLUSIONS: Pre-existing ILD was a significant risk factor for
      symptomatic and severe RP. Prescreening for ILD findings is important for
      determining the radiation pneumonitis risk when planning SBRT.

PMID- 25376514
TI  - Stereotactic body radiotherapy for lung cancer: how much does it really cost?
AB  - INTRODUCTION: Despite the lack of randomized evidence, stereotactic body
      radiotherapy (SBRT) is being accepted as superior to conventional radiotherapy
      for patients with T1-2N0 non-small-cell lung cancer in the periphery of the lung
      and unfit or unwilling to undergo surgery. To introduce SBRT in a system of
      coverage with evidence development, a correct financing had to be determined.
      METHODS: A time-driven activity-based costing model for radiotherapy was
      developed. Resource cost calculation of all radiotherapy treatments, standard and
      innovative, was conducted in 10 Belgian radiotherapy centers in the second half
      of 2012. RESULTS: The average cost of lung SBRT across the 10 centers
      (6221&OV0556;) is in the range of the average costs of standard fractionated 3D
      conformal radiotherapy (5919&OV0556;) and intensity-modulated radiotherapy
      (7379&OV0556;) for lung cancer. Hypofractionated 3D-conformal radiotherapy and
      intensity-modulated radiotherapy schemes are less costly (3993&OV0556;
      respectively 4730&OV0556;). The SBRT cost increases with the number of fractions
      and is highly dependent of personnel and equipment use. SBRT cost varies more by
      centre than conventional radiotherapy cost, reflecting different technologies,
      stages in the learning curve and a lack of clear guidance in this field.
      CONCLUSIONS: Time-driven activity-based costing of radiotherapy is feasible in a
      multicentre setup, resulting in real-life resource costs that can form the basis
      for correct reimbursement schemes, supporting an early yet controlled
      introduction of innovative radiotherapy techniques in clinical practice.

PMID- 25376513
TI  - EGFR mutation testing practices within the Asia Pacific region: results of a
      multicenter diagnostic survey.
AB  - INTRODUCTION: The efficacy of epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer (NSCLC)
      patients necessitates accurate, timely testing. Although EGFR mutation testing
      has been adopted by many laboratories in Asia, data are lacking on the proportion
      of NSCLC patients tested in each country, and the most commonly used testing
      methods. METHODS: A retrospective survey of records from NSCLC patients tested
      for EGFR mutations during 2011 was conducted in 11 Asian Pacific countries at 40
      sites that routinely performed EGFR mutation testing during that period. Patient
      records were used to complete an online questionnaire at each site. RESULTS: Of
      the 22,193 NSCLC patient records surveyed, 31.8% (95% confidence interval: 31.2%
      32.5%) were tested for EGFR mutations. The rate of EGFR mutation positivity was
      39.6% among the 10,687 cases tested. The majority of samples were biopsy and/or
      cytology samples (71.4%). DNA sequencing was the most commonly used testing
      method accounting for 40% and 32.5% of tissue and cytology samples, respectively.
      A pathology report was available only to 60.0% of the sites, and 47.5% were not
      members of a Quality Assurance Scheme. CONCLUSIONS: In 2011, EGFR mutation
      testing practices varied widely across Asia. These data provide a reference
      platform from which to improve the molecular diagnosis of NSCLC, and EGFR
      mutation testing in particular, in Asia.

PMID- 25376515
TI  - Neighborhood deprivation and lung cancer incidence and mortality: a multilevel
      analysis from Sweden.
AB  - BACKGROUND: Neighborhood deprivation has been implicated in lung cancer but no
      study has simultaneously analyzed the potential effect of neighborhood
      deprivation on both lung cancer incidence and mortality, after adjusting for
      individual-level socioeconomic factors, and comorbidities. The aim of this study
      was to analyze whether there is an association between neighborhood deprivation
      and incidence and mortality rates of lung cancer, beyond individual-level
      characteristics. DESIGN: The incident and mortality cases of lung cancer were
      determined in the entire Swedish population aged over 50 (3.2 million
      individuals) between 2000 and 2010. Multilevel logistic regression was used in
      the analysis with individual-level characteristics (age, marital status, family
      income, education, immigration status, urban/rural status, mobility, and
      comorbidities) at the first level and level of neighborhood deprivation at the
      second level. A neighborhood deprivation index, constructed from the variables
      education, income, unemployment, and welfare assistance, was used to assess the
      level of neighborhood deprivation. RESULTS: There was a strong association
      between level of neighborhood deprivation and incidence and mortality of lung
      cancer. In the fully adjusted model, the odds of lung cancer were 1.27 and 1.32,
      respectively, in the most deprived neighborhood. The between-neighborhood
      variance (i.e., the random intercept) was over 1.96 times the standard error in
      all models, indicating that there were significant differences in incidence and
      mortality rates of lung cancer between neighborhoods. CONCLUSIONS: Results
      suggest that neighborhood deprivation is associated with incident and mortality
      cases of lung cancer in Sweden, independently of individual-level
      characteristics.

PMID- 25376516
TI  - Racial diversity of actionable mutations in non-small cell lung cancer.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer-related deaths in the
      US. The reasons for higher incidence and poorer survival rates among black
      compared with white lung cancer patients have not been defined. We hypothesized
      that differential incidence of somatic cancer gene mutations may be a
      contributing factor. Previous genomic studies of non-small cell lung cancer
      (NSCLC) have not adequately represented black patients. METHODS: A matrix
      assisted laser desorption/ionization and time-of-flight mass spectrometry
      approach was used to analyze tumor DNA for 214 coding mutations in 26 cancer
      genes previously identified in NSCLC. The samples included NSCLC from 335 white
      patients and 137 black patients. For 299 of these, normal matched DNA was
      available and analyzed. RESULTS: Epidermal growth factor receptor (EGFR) exon 19
      deletions were only detected in women cases, with increased odds for black women
      compared with white women (odds ratio = 3.914, 95% confidence interval: 1.014
      15.099, p = 0.048). Beyond race, variations in mutation frequencies were seen by
      histology. DDR2 alterations, previously described as somatic mutations, were
      identified as constitutional variants. CONCLUSIONS: This study is among the
      largest comparing somatic mutations in black and white patients. The results
      point to the molecular diversity of NSCLC and raise new questions as to the
      importance of inherited alleles. Genomic tumor testing will benefit both
      populations, although the mutation spectrum appears to vary by sex, race, and
      histology.

PMID- 25376517
TI  - Autosis occurs in the liver of patients with severe anorexia nervosa.

PMID- 25376518
TI  - Methods for exploring treatment effect heterogeneity in subgroup analysis: an
      application to global clinical trials.
AB  - Multi-country randomised clinical trials (MRCTs) are common in the medical
      literature, and their interpretation has been the subject of extensive recent
      discussion. In many MRCTs, an evaluation of treatment effect homogeneity across
      countries or regions is conducted. Subgroup analysis principles require a
      significant test of interaction in order to claim heterogeneity of treatment
      effect across subgroups, such as countries in an MRCT. As clinical trials are
      typically underpowered for tests of interaction, overly optimistic expectations
      of treatment effect homogeneity can lead researchers, regulators and other
      stakeholders to over-interpret apparent differences between subgroups even when
      heterogeneity tests are insignificant. In this paper, we consider some
      exploratory analysis tools to address this issue. We present three measures
      derived using the theory of order statistics, which can be used to understand the
      magnitude and the nature of the variation in treatment effects that can arise
      merely as an artefact of chance. These measures are not intended to replace a
      formal test of interaction but instead provide non-inferential visual aids, which
      allow comparison of the observed and expected differences between regions or
      other subgroups and are a useful supplement to a formal test of interaction. We
      discuss how our methodology differs from recently published methods addressing
      the same issue. A case study of our approach is presented using data from the
      Study of Platelet Inhibition and Patient Outcomes (PLATO), which was a large
      cardiovascular MRCT that has been the subject of controversy in the literature.
      An R package is available that implements the proposed methods.

PMID- 25376519
TI  - Multivalency as a key factor for high activity of selective supported
      organocatalysts for the Baylis-Hillman reaction.
AB  - The polystyrene-supported N-alkylimidazole-based dendritic catalysts for the
      Baylis-Hillman reaction exhibit one of the strongest beneficial effects of
      multivalent architecture ever reported for an organocatalyst. The yields in the
      model reaction of methyl vinyl ketone with p-nitrobenzaldehyde are more than
      tripled when a non-dendritic catalyst is replaced by a second- or third
      generation analogue. Moreover, the reaction of the less active substrates will
      not occur with the non-dendritic catalyst and will proceed to a significant
      extent only with the analogous catalysts of higher generations. A substantial
      additional enhancement of the reaction yield could be achieved by increasing the
      content of water in the reaction solvent. The plausible cause of the dendritic
      effect is the assistance of the second, nearby imidazole moiety in the presumably
      rate-determining proton transfer in the intermediate adduct, after the first
      imidazole unit induced the formation of the new carbon-carbon bond. 

PMID- 25376520
TI  - Moral distance and distributive justice: how the increase in organ donation is
      helping us make better ethical decisions.

PMID- 25376521
TI  - Adventitious ventilation: a new definition for an old mode?

PMID- 25376522
TI  - Formation of reactive oxygen species in granulocytes is not inflammation.

PMID- 25376523
TI  - Response to correspondence by Johan Ovrevik.

PMID- 25376525
TI  - Crystallographic snapshot of an arrested intermediate in the biomimetic
      activation of CO2.
AB  - The design of molecular catalysts that mimic the behavior of enzymes is a topical
      field of activity in emerging technologies, and can lead to an improved
      understanding of biological systems. Herein, we report how the bulky arms of the
      cations in [(n C4 H9 )4 N](+) [HCO3 ](-) give rise to a host scaffold that
      emulates the substrate binding sites in carbonic anhydrase enzymes, affording a
      unique glimpse of an arrested intermediate in the base-mediated binding and
      activation of CO2 . 

PMID- 25376524
TI  - Germline PTEN, SDHB-D, and KLLN alterations in endometrial cancer patients with
      Cowden and Cowden-like syndromes: an international, multicenter, prospective
      study.
AB  - BACKGROUND: Endometrial cancer has been recognized only recently as a major
      component of Cowden syndrome (CS). Germline alterations in phosphatase and tensin
      homolog (PTEN; PTEN_mut+), succinate dehydrogenase B/C/D (SDHB-D; SDHx_var+), and
      killin (KLLN_Me+) cause CS and Cowden syndrome-like (CSL) phenotypes. This study
      was aimed at identifying the prevalence and clinicopathologic predictors of
      germline PTEN_mut+, SDHx_var+, and KLLN_Me+ in CS/CSL patients presenting with
      endometrial cancer. METHODS: PTEN and SDHB-D mutation and KLLN promoter
      methylation analyses were performed for 371 prospectively enrolled patients (2005
      2011). PTEN protein was analyzed from patient-derived lymphoblast lines. The PTEN
      Cleveland Clinic (CC) score is a weighted, regression-based risk calculator
      giving the a priori risk for PTEN_mut+. Demographic and clinicopathologic
      features were correlated with the specific gene. RESULTS: Germline PTEN_mut+,
      SDHx_var+, and KLLN_Me+ were found in 7%, 9.8%, and 10.5% of informative samples,
      respectively. Predictors of PTEN_mut+ included an age <= 50 years (odds ratio
      [OR] for an age < 30 years, 6.1 [P = .015]; OR for an age of 30-50 years, 4.4 [P
      = .001]), macrocephaly (OR, 14.4; P < .001), a higher CC score (OR for a 1-U
      increment, 1.35; P < .001), a PTEN protein level within the lowest quartile (OR,
      5.1; P = .039), and coexisting renal cancer (OR, 5.7; P = .002). KLLN_Me+
      patients were on average 8 years younger than KLLN_Me- patients (44 vs 52 years,
      P = .018). Predictors of KLLN_Me+ were a younger age and a higher CC score. On
      the other hand, no clinical predictors of SDH_var+ were found. CONCLUSIONS:
      Clinical predictors of PTEN and KLLN alterations, but not SDHx_var+, were
      identified. These predictors should alert the treating physician to potential
      heritable risk and the need for referral to genetic professionals. High-risk
      cancer surveillance and prophylactic surgery of the uterus may be considered for
      KLLN_Me+ patients similarly to PTEN_mut+ patients.

PMID- 25376526
TI  - Effect of nocturnal haemodialysis on body composition.
AB  - BACKGROUND: Haemodialysis patients have a high risk of malnutrition which is
      associated with increased mortality. Nocturnal haemodialysis (NHD) is associated
      with a significant increase in protein intake compared with conventional
      haemodialysis (CHD). It is unclear whether this leads to improved nutritional
      status. Therefore, we studied whether 1 year of NHD is associated with a change
      in body composition. METHODS: Whole-body composition using dual-energy X-ray
      absorptiometry (DEXA) and normalised protein catabolic rate (nPCR) were measured
      in 11 adult patients before and 1 year after the transition from CHD (12 h
      dialysis/week) to NHD (28-48 h dialysis/week). Similar measurements were
      performed in a matched control group of 13 patients who stayed on CHD.
      Differences between groups were analysed with linear mixed models. RESULTS: At
      baseline, nPCR, total mass, fat-free mass, and fat mass did not differ
      significantly between the CHD and NHD groups. nPCR increased in the NHD group
      (from 0.96 +/- 0.23 to 1.12 +/- 0.20 g/kg/day; p = 0.027) whereas it was stable
      in the CHD group (0.93 +/- 0.21 at baseline and 0.87 +/- 0.09 g/kg/day at 1 year,
      n.s.). The change in nPCR differed significantly between the two groups (p =
      0.027). We observed no significant differences in the course of total mass, fat
      free mass, and fat mass during the 1-year observation period between the NHD and
      CHD groups. CONCLUSIONS: One year of NHD had no significant effect on body
      composition in comparison with CHD, despite a significantly higher protein intake
      in patients on NHD.

PMID- 25376527
TI  - Blood flows in tributaries of the portal vein: anatomical and angiographic
      studies in normal beagle dogs.
AB  - Liver anatomy, particularly its vascularization, has been investigated in many
      studies in dogs. Knowledge of blood flow from the main tributaries of the portal
      vein (PV) is necessary to explain the preferential sites of secondary lesions
      within the liver based on the site of the initial malignant lesion. How these
      flows come together was established in an earlier ex vivo study. Here, we
      highlight in vivo the blood flows from the main PV tributaries and their
      distribution in the liver of normal dogs. Portographs of the main PV tributaries
      were obtained in seven dogs after injection of an angiographic contrast medium.
      After euthanasia, the livers and their portal vascularization (PV and
      tributaries) were extracted for a comparative corrosion cast study. Flows were
      demonstrated in the cranial mesenteric vein, caudal mesenteric vein and splenic
      vein. However, no proper flow could be distinguished for the gastroduodenal and
      ileocolic veins. All these tributaries primarily supply the lateral liver lobes
      (right or left). Most of our observations indicate that the cranial mesenteric,
      caudal mesenteric and splenic veins primarily supply the right lateral lobe and
      the caudate process of the caudate lobe and secondarily the left lateral lobe,
      left medial lobe and the quadrate lobe. The two other tributaries (gastroduodenal
      and ileocolic veins) primarily supply the right lateral lobe and the caudate
      process of the caudate lobe. 

PMID- 25376528
TI  - Relation of the rs6923761 gene variant in glucagon-like peptide 1 receptor to
      metabolic syndrome in obese subjects.
AB  - BACKGROUND: The role of glucagon-like peptide 1 (GLP-1) variants in metabolic
      syndrome (MS) and its components remains unclear in obese subjects. OBJECTIVE:
      The aim of our study was to evaluate the relationship of rs6923761 with MS and
      its components in obese subjects. DESIGN: A population of 1,122 obese subjects
      was analyzed in a cross-sectional survey. To estimate the prevalence of MS, we
      considered the definitions of the Adult Treatment Panel III. RESULTS: Five
      hundred and forty-eight patients (48.8%) had the GG genotype (wild-type group),
      whereas 487 patients (43.4%) had the GA genotype and 87 patients (7.8%) the AA
      genotype. The mean age was 48.9 +/- 12.8 years. The prevalence of MS was 47.4%
      (532 patients), and 52.6% of patients had no MS (n = 590). The odds ratio of MS
      for the wild-type versus the mutant genotype was 1.02, with a 95% confidence
      interval of 0.88-1.12. Body mass index, weight, fat mass, waist circumference,
      and waist to hip ratio were lower in the mutant than in the wild-type group in
      patients with and without MS. CONCLUSION: The GLP-1 receptor variant rs6923761
      was found to be associated with decreased weight and anthropometric parameters in
      A allele carriers with and without MS. MS or its components were not associated
      with this polymorphism in obese adults.

PMID- 25376529
TI  - Solution-processable carbazole-based conjugated dendritic hosts for power
      efficient blue-electrophosphorescent devices.
AB  - A novel class of hosts suitable for solution processing has been developed based
      on a conjugated dendritic scaffold. By increasing the dendron generation, the
      highest occupied molecular orbital (HOMO) energy level can be tuned to facilitate
      hole injection, while the triplet energy remains at a high level, sufficient to
      host high-energy-triplet emitters. A power-efficient blue-electrophosphorescent
      device based on H2 is presented. 

PMID- 25376530
TI  - Critical success factors in awareness of and choice towards low vision
      rehabilitation.
AB  - PURPOSE: The goal of the current study was to examine the critical factors
      indicative of an individual's choice to access low vision rehabilitation
      services. METHODS: Seven hundred and forty-nine visually impaired individuals,
      from the Montreal Barriers Study, completed a structured interview and
      questionnaires (on visual function, coping, depression, satisfaction with life).
      Seventy-five factors from the interview and questionnaires were entered into a
      data-driven Classification and Regression Tree Analysis in order to determine the
      best predictors of awareness group: positive personal choice (I knew and I went),
      negative personal choice (I knew and did not go), and lack of information (Nobody
      told me, and I did not know). RESULTS: Having a response of moderate to no
      difficulty on item 6 (reading signs) of the Visual Function Index 14 (VF-14)
      indicated that the person had made a positive personal choice to seek
      rehabilitation, whereas reporting a great deal of difficulty on this item was
      associated with a lack of information on low vision rehabilitation. In addition
      to this factor, symptom duration of under nine years, moderate difficulty or less
      on item 5 (seeing steps or curbs) of the VF-14, and an indication of little
      difficulty or less on item 3 (reading large print) of the VF-14 further
      identified those who were more likely to have made a positive personal choice.
      Individuals in the lack of information group also reported greater difficulty on
      items 3 and 5 of the VF-14 and were more likely to be male. CONCLUSIONS: The
      duration-of-symptoms factor suggests that, even in the positive choice group, it
      may be best to offer rehabilitation services early. Being male and responding
      moderate difficulty or greater to the VF-14 questions about far, medium-distance
      and near situations involving vision was associated with individuals that lack
      information. Consequently, these individuals may need additional education about
      the benefits of low vision services in order to make a positive personal choice.

PMID- 25376531
TI  - Reusable nanocopy machine particles for the replication of DNA.
AB  - As one of the most important components copying DNA molecules in the PCR system,
      Taq DNA polymerase has a high processivity, however, lower persistence when
      compared to other polymerases. Studies for the enhancement of stability of Taq
      DNA polymerase is of great importance. The present study describes the
      integration of PCR application of cross-linked Taq DNA polymerase enzyme in a
      nanochamber using a ruthenium based MATyr-Ru-(bipyr)2)-MATyr monomer hapten
      prepared by photosensitive microemulsion polymerization technique. The
      conjugation and cross-linking have achieved using our previously invented
      Aminoacid (monomer) Decorated and Light Underpining Conjugation Approach
      (ANADOLUCA) method. Microemulsion polymerization media has prepared by dispersing
      PVA in deionized water. The nano enzyme could be easily prepared at room
      temperature, in daylight and under nitrogen atmosphere using ruthenium based
      photosensitive cross-linking agents. The nano copy machine particles (nano Taq
      DNA polymerase) are very stable against more acidic or more basic conditions,
      high temperatures and could be reusable in PCR analysis for many times without
      any deformation in their structures.

PMID- 25376532
TI  - A novel fish cell line derived from the brain of Chinese perch Siniperca chuatsi:
      development and characterization.
AB  - In this study, a continuous cell line (named as CPB) was established from
      Siniperca chuatsi brain and has been subcultured >140 times. CPB cell line
      predominantly consisted of fibroblast-like cells that could grow better in
      Leibovitz's L-15 supplemented with 10% foetal bovine serum at 28 degrees  C.
      Polymerase chain reaction amplification of 18s recombinant (r)RNA confirmed the
      origin of this cell line from S. chuatsi. The CPB cell line was cryopreserved at
      different passage levels and revived successfully with 80-90% survival. The cell
      line was further characterized by chromosome number and transfection. The CPB
      cells were highly susceptible to infectious spleen and kidney necrosis virus
      (ISKNV) with a titre of 6.58-6.62 log TCID50 ml(-1) and numerous ISKNV particles
      were observed in the cytoplasm by transmission electron microscopy. At the same
      time, ISKNV infection was confirmed by reverse transcriptase polymerase chain
      reaction, immunodot blot and individual challenge experiments. The development
      and characterization of a new brain cell line from S. chuatsi were described in
      this study and it could be used as an in vitro tool for propagation of ISKNV and
      gene expression studies. 

PMID- 25376533
TI  - Autoantibodies isolated from patients with preeclampsia induce soluble endoglin
      production from trophoblast cells via interactions with angiotensin II type 1
      receptor.
AB  - PROBLEM: This study investigated whether angiotensin II type 1 receptor agonistic
      autoantibodies (AT1 -AAs) mediate the increased release of soluble endoglin
      (sEng) in women with preeclampsia. METHOD OF STUDY: Serum samples were obtained
      from women with normal pregnancies or with preeclampsia. Human first-trimester
      trophoblast cells were cultured with purified IgG derived from these sera, and
      the sEng protein and mRNA expression levels were measured in the supernatants. We
      also determined the effects of the AT1 -AAs on these cells following treatment
      with an AT1 receptor antagonist (losartan). RESULTS: Compared with the IgG
      isolated from the women with normal pregnancies, treatments of the preeclamptic
      patients markedly increased sEng production and mRNA expression in trophoblast
      cells. Co-treatment with losartan significantly attenuated the release of sEng
      and sEng mRNA expression in the trophoblast cells. CONCLUSION: AT1 -AAs may be
      related to the increased release of sEng observed during preeclampsia and may
      play important roles in the pathology of this disorder.

PMID- 25376534
TI  - Glycogen pathways in disease: new developments in a classical field of medical
      genetics.
AB  - Glycogen is the storage form of glucose in animal cells. Its degradation can
      rapidly provide fuel for energy production (particularly important in muscle), or
      replenish blood glucose during fasting by the liver. Genetic defects of glycogen
      metabolism give rise to glycogen storage diseases (GSDs), manifesting
      histologically in abnormal quantity or quality of glycogen in the cells. GSDs can
      be caused by defects of proteins participating in the synthesis or degradation of
      glycogen itself, in the glycolytic degradation of glucose phosphates in muscle
      and erythrocytes, in the release of glucose from liver and kidney into the
      bloodstream, in the clearance of glycogen from lysosomes (all, "primary GSDs"),
      or in the control of these pathways ("secondary GSDs"). Most genes responsible
      for classical, primary GSDs have probably been identified, and future progress in
      understanding the biochemical and genetic defects underlying unsolved disorders
      presenting with glycogen storage abnormalities will perhaps be predominantly in
      the field of secondary GSDs. 

PMID- 25376535
TI  - The clinical features and histopathologic patterns of folliculotropic mycosis
      fungoides in a series of 38 cases.
AB  - BACKGROUND: The recognition of folliculotropic mycosis fungoides (FMF) may pose
      diagnostic challenges, owing to the variety of histopathological findings.
      OBJECTIVE: In this study, our aim is to describe the broad spectrum of the
      histopathological patterns in a total of 86 biopsies from 38 patients with FMF,
      together with the clinical features. RESULTS: The most frequent histopathologic
      pattern was the folliculocentric/folliculotropic pattern, with or without
      follicular mucinosis. Keratin-filled cysts and comedones were the second most
      common pattern in the biopsies. Other less common findings included widening of
      the hair follicle orifis with keratotic plugging, reminiscent of keratosis
      pilaris, granuloma formation, eosinophilic or suppurative folliculitis and
      basaloid folliculolymphoid hyperplasia. Coexisting syringotropism was present in
      some biopsies. The CD4 : CD8 ratio was at least 4 : 1 or more in most biopsies.
      Grouped follicular papules and patch/plaque lesions with follicular prominence
      were the most frequent clinical findings. Folliculocentric lesions such as milia,
      cysts and acneiform lesions, alopecia, loss of hair or eyebrows were also seen.
      In 6 out of 38 (15.8%) patients, transformation to large-cell lymphoma was
      observed during the follow-up. CONCLUSION: The awareness and the identification
      of the various histopathological presentations of FMF by pathologists, as well as
      by clinicians, are imperative to prevent diagnostic errors.

PMID- 25376536
TI  - Efficacy of dental floss impregnated with chlorhexidine on reduction of
      supragingival biofilm: a randomized controlled trial.
AB  - BACKGROUND: The use of a toothbrush has a limited ability to control the dental
      biofilm in interproximal areas. Therefore, specialized devices, such as dental
      floss, may be useful for these specific areas. OBJECTIVE: This study aimed to
      investigate the efficacy of dental floss impregnated with 5% chlorhexidine
      gluconate on the reduction of the supragingival biofilm. METHODS: This research
      was parallel, single-blind, controlled and randomized, and contained a sample of
      thirty dental students from the Faculty of Pharmacy, Dentistry and Nursing of the
      Federal University of Ceara, Brazil, who were divided equally into three groups.
      The negative control group (NC) did not utilize any kind of interproximal
      cleaning; the positive control group (PC) used waxed floss without impregnation
      twice a day; and the test group (T) used the same dental floss, which was
      impregnated with 5% chlorhexidine gluconate, twice a day. For all groups, this
      study lasted for 15 days. The presence of a biofilm was evaluated on four
      surfaces (mesiobuccal, distobuccal, mesiolingual and distolingual) by the Quigley
      Hein Index, resulting in four scores for each tooth. RESULTS: Group T had the
      lowest plaque scores, showing a significant difference compared to group NC (P <
      0.001) and group PC (P < 0.001). Group PC also displayed a significant difference
      compared to NC (P < 0.001). CONCLUSION: It was concluded that the use of dental
      floss impregnated with 5% chlorhexidine gluconate resulted in additional
      reductions in the supragingival biofilm relative to the results achieved with
      conventional waxed floss on the anterior teeth of a well-motivated and well
      instructed population.

PMID- 25376537
TI  - In vivo markers of Parkinson's disease and dementia with Lewy bodies: current
      value of the 5G4 alpha-synuclein antibody.

PMID- 25376538
TI  - Conceptualizing acts and behaviours that comprise intimate partner violence: a
      concept map.
AB  - BACKGROUND: This study aims to explore the conceptualization of intimate partner
      violence (IPV) among men and women from diverse subpopulations in Toronto, ON,
      Canada. Relatively few research efforts have been made to examine differences in
      conceptualizations of IPV across populations of different race and ethnic
      backgrounds. METHODS: Using concept mapping methodology, we sampled 67 women and
      men identified concepts and groups of concepts (domains) that reflected their
      understandings of the behaviours and attitudes that comprised IPV. We also
      determined the relative importance of each concept and domain as a contributor to
      IPV. RESULTS: 'External and Cultural Influences', 'Victim Response to Abuse' and
      'Social and Emotional Manipulation' were a few domains that participants rated as
      moderately or highly important contributors to IPV. These conceptual domains are
      often left out of commonly used IPV measures. CONCLUSIONS: Our findings have
      important implications for the conceptualization of IPV and for future IPV
      measurement and measurement tool development.

PMID- 25376539
TI  - [Experiences and recommendations of the German Federal Institute for Drugs and
      Medical Devices (BfArM) concerning clinical investigation of medical devices and
      the evaluation of serious adverse events (SAE)].
AB  - An integral part of the conformity assessment process for medical devices is a
      clinical evaluation based on clinical data. Particularly in the case of
      implantable devices and products of risk class III clinical trials must be
      performed. Since March 2010 applications for the authorization of clinical trials
      as well as for the waiver of the authorization requirement must be submitted
      centrally in Germany to the appropriate federal authority, the Federal Institute
      for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). In
      addition to authorization, approval by the responsible ethics committee is also
      required under law in order to begin clinical testing of medical devices in
      Germany. In this paper, the legal framework for the clinical testing of medical
      devices as well as those involved and possible procedures including evaluation
      criteria for the initial application of a trial and subsequent amendments are
      presented in detail. In addition, the reporting requirements for serious adverse
      events (SAEs) are explained and possible consequences of the evaluation are
      presented. Finally, a summary of application and registration numbers for all
      areas of extensive experience of the BfArM as well as requests and guidance for
      applicants are presented. 

PMID- 25376540
TI  - Generation of cytotoxic T lymphocytes specific for native or modified peptides
      derived from the epidermal growth factor receptor pathway substrate 8 antigen.
AB  - The ideal tumor antigen for the development of a cancer immunotherapy is one that
      is expressed only in tumor cells. The epidermal growth factor receptor pathway
      substrate 8 gene (Eps8) might be an effective antigen for cancer immunotherapy as
      it is overexpressed in a variety of cancer cells but not in normal tissues. In
      this study, the potential utility of an Eps8-derived immunotherapy was tested in
      vitro and in vivo. Three computer-based algorithms were used to design eight Eps8
      native epitopes with potentially high binding affinity to the HLA-A2.1 molecule,
      which is found at a high frequency in the Chinese population. Of these eight,
      three peptides with a moderate affinity to the HLA-A2.1 molecule were modified at
      anchor residue positions to achieve stronger immunogenicity. These four modified
      peptides displayed stronger binding affinity to HLA-A2.1 molecules on T2 cells
      and a lower dissociation rate. In functional assays with human PBMCs in vitro and
      in HLA-A2.1/K(b) transgenic mice in vivo, CTLs primed by each native and modified
      peptide secreted IFN-gamma and were toxic to cancer cells from a variety of
      tissue types in an HLA-A2.1-restricted and Eps8-specific manner. p101-109-2L and
      p276-284-1Y9V were superior to other modified and native epitopes both in vitro
      and in vivo. These results indicate that employing the native and modified
      epitopes identified here in Eps8-based immunotherapy for HLA-A2.1 positive cancer
      patients may result in efficient anticancer immune responses for diverse tumor
      types. 

PMID- 25376541
TI  - Expression and function of Toll-like receptors in peripheral blood mononuclear
      cells from patients with ovarian cancer.
AB  - Inflammation has been implicated in the initiation and progression of ovarian
      cancer (OC), the underlying mechanisms of which are still unclear. We
      hypothesized that the abnormal expression of Toll-like receptors (TLRs), which
      were potential activators of nuclear factor-kappa B p65 (NF-kappaB p65), could
      promote inflammation and tumorigenesis in OC. In this study, we characterized the
      expression of TLRs in peripheral blood mononuclear cells (PBMCs) and found TLR2
      and TLR6 mRNAs levels to be higher in PBMCs from OC patients than in those from
      benign disease (BC) or healthy normal controls (NC). Flow cytometry analysis
      showed that TLR1, TLR2 and TLR6 were highly expressed in monocytes from OC
      patients, but not in those from control subjects. Consistently, inflammatory
      cytokines interleukin (IL)-1beta and IL-6 were up-regulated in PBMCs from OC
      patients upon stimulation with Pam3CSK4 (TLR1 ligand) and HKLM (TLR2 ligand),
      compared with unstimulated PBMCs. Stimulation of PBMCs with TLR ligands led to
      activation of downstream signaling molecules in TLRs (MyD88, TRAF6, TANK, NF
      kappaB p65 and p-NF-kappaB p65). We also discovered that SK-OV-3-secreted factors
      were potent PBMCs activators, leading to the production of IL-1beta, IL-6 and IL
      8 through activation of TLRs and downstream signaling molecules in PBMCs. Before
      coculturing with SK-OV-3, pretreatment of THP-1 cells or PBMCs with monoclonal
      antibodies against TLR1, TLR2 or TLR6 inhibited the production of IL-1beta and IL
      6 and activation of MyD88, TRAF6, TANK, NF-kappaB p65 and p-NF-kappaB p65. Our
      results provided new evidence that TLR1, TLR2 and TLR6 signaling was linked with
      inflammation in OC microenvironment. 

PMID- 25376543
TI  - Marked decrease in serum pepsinogen II levels resulting from endoscopic resection
      of a large duodenal tumor.
AB  - Studies have indicated that serum pepsinogen (PG) levels are not only markers for
      chronic atrophic gastritis but also predictive risk factors for gastric cancer.
      However, serum PG levels can change because of pathological conditions other than
      gastritis. We report the first case in which abnormally high serum PG II levels
      (168.8 ng/mL) led to the discovery of a large tumor covering a wide area in the
      duodenum, and after resection of the tumor, the serum PG II levels markedly
      decreased. Because endoscopic and histopathological examinations showed no
      indications of atrophic changes, inflammation of the gastric mucosa, or
      Helicobacter pylori infection, the serum PG II levels eventually returned to
      normal (10.1 ng/mL). The preoperative abnormally high PG II levels were probably
      caused by the large duodenal tumor that prevented PG II (which is produced by the
      duodenal Brunner's glands) from being secreted into the lumen, a condition that
      increased the amount transferred to the bloodstream. No previous reports have
      investigated serum PG II levels before and after resection of a large duodenal
      tumor. We believe this case provides valuable insight regarding the dynamics of
      PG II in the body and has important diagnostic implications.

PMID- 25376542
TI  - Immunological changes after ASIT in AD allergen-specific immunotherapy and their
      potential correlation with clinical response in patients with atopic dermatitis
      patients sensitized to house dust mite.
AB  - BACKGROUND: Allergen-specific immunotherapy (ASIT) is the main treatment for
      inducing long-term immunological and clinical tolerance in patients with IgE
      mediated allergic diseases. Recent open-label and controlled studies on the
      efficacy of ASIT in patients with atopic dermatitis (AD) have provided promising
      results. However, data about possible relationship between the improvement of
      clinical symptoms and changes of serum cytokines are limited. METHODS: Seventy
      nine patients with moderate to severe AD sensitized to house dust mite (HDM) were
      enrolled. Fifty-eight patients were treated with ASIT and 11 controls received
      only symptomatic treatment. The disease activity in AD patients was evaluated by
      using the patient-oriented eczema measure (POEM) system. Serum interleukin (IL)
      4, IL-10, interferon (IFN)-gamma, transforming growth factor (TGF) beta1, total
      IgE, HDM-specific IgE (s-IgE) and HDM-specific IgG4 (s-IgG4) were measured before
      and after 2 years of therapy. RESULTS: The mean patient-oriented eczema measure
      system (POEM) score of AD patients with ASIT significantly decreased after 2
      years of treatment, compared to that in patients without ASIT. After ASIT, the
      serum levels of IL-10, TGF-beta1, IFN-gamma and s-IgG4 increased, while the level
      of IL-4 decreased. The change in the POEM score was negatively correlated with
      changes of serum concentration of TGF-beta1, s-IgG4 and IFN-gamma. Furthermore, s
      IgG4 levels were positively correlated with changes in the IL-10 levels. No
      correlation between POEM score and serum IL-10 or IL-4 was observed. CONCLUSION:
      Clinical symptoms and the quality of life of AD with HDM sensitization could be
      improved after 2 years of ASIT. Changes in serum IL-10, TGF-beta1, s-IgG4 and IFN
      gamma might be considered as biomarkers to assist clinical evaluation of the
      therapeutic effects of ASIT in patients with AD.

PMID- 25376544
TI  - Subsets of a large cognitive battery better power clinical trials on early stage
      Alzheimer's disease.
AB  - BACKGROUND/AIMS: Cognitive batteries routinely used by the Alzheimer's disease
      (AD) research community may contain items that are uninformative for tracking
      disease progression to power clinical trials on early stage AD. We aim to
      identify the subsets of the most informative items from an existing cognitive
      battery to better power clinical trials on early AD. METHODS: Longitudinal change
      in item scores from the battery was associated with the onset of mild cognitive
      impairment (MCI) in 1,513 elderly individuals. Items whose longitudinal changes
      were correlated with the onset of MCI were selected as informative for tracking
      the early cognitive progression. RESULTS: 226 items in the battery were annually
      assessed over a follow-up of up to 13 years. Changes of item scores over time
      from 187 items were significantly correlated with the onset of MCI. For clinical
      trials on preclinical AD and on MCI, informative items permit smaller or similar
      sample sizes as compared to the entire battery, whereas uninformative items
      require much larger sample sizes. CONCLUSIONS: Longitudinal changes in item
      scores from about 17% of items in the cognitive battery are uninformative for
      tracking early disease progression. Clinical trials on early AD can be better
      powered using informative items rather than the entire battery.

PMID- 25376545
TI  - [Opioids in chronic noncancer pain-are opioids different? A systematic review and
      meta-analysis of efficacy, tolerability and safety in randomized head-to-head
      comparisons of opioids of at least four week's duration].
AB  - BACKGROUND: We updated a systematic review on the comparative efficacy,
      tolerability and safety of opioids and of their routes of application in chronic
      noncancer pain (CNCP). METHODS: We screened MEDLINE, Scopus and the Cochrane
      Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as
      the reference sections of original studies and systematic reviews of randomized
      controlled trials (RCTs) of opioids in CNCP. We included randomized head-to-head
      comparisons of opioids (opioid of the sponsor of the study versus standard
      opioid) of at least 4 week's duration. Using a random effects model, absolute
      risk differences (RD) were calculated for categorical data and standardized mean
      differences (SMD) for continuous variables. The quality of evidence was rated by
      the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)
      approach. RESULTS: We included 13 RCTs with 6748 participants. Median study
      duration was 15 weeks (range 4-56 weeks). Hydromorphone, morphine, oxymorphone
      and tapentadol were compared to oxycodone; fentanyl to morphine and buprenorphine
      to tramadol. In pooled analysis, there were no significant differences between
      the two groups of opioids in terms of mean pain reduction (low-quality evidence),
      the patient global impression to be much or very much improved outcome (low
      quality evidence), physical function (very low-quality evidence), serious adverse
      events (moderate-quality evidence) or mortality (moderate-quality evidence).
      There was no significant difference between transdermal and oral application of
      opioids in terms of mean pain reduction, physical function, serious adverse
      events, mortality (all low-quality evidence) or dropout due to adverse events
      (very low-quality). CONCLUSION: Pooled head-to-head comparisons of opioids
      (opioid of the sponsor of the study versus standard opioid) provide no rational
      for preferring one opioid and/or administration route over another in the therapy
      of patients with CNCP. The English full-text version of this article is freely
      available at SpringerLink (under "Supplemental").

PMID- 25376546
TI  - [Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics?
      A systematic review and meta-analysis of efficacy, tolerability and safety in
      randomized head-to-head comparisons of opioids versus nonopioid analgesics of at
      least four week's duration].
AB  - BACKGROUND: Some leading German pain medicine experts postulate that there is a
      type of chronic non-cancer pain (CNCP) with an opioid requirement. We tested
      whether opioids are superior to nonopioid analgesics in the management of CNCP in
      studies of at least 4 week's duration. METHODS: We screened MEDLINE, Scopus and
      the Cochrane Central Register of Controlled Trials (CENTRAL) up until October
      2013, as well as the reference sections of original studies and systematic
      reviews of randomised controlled trials (RCTs) of opioids in CNCP. We included
      double-blind RTCs comparing opioids to nonopioid analgesics of at least 4 week's
      duration. Relative risks differences (RD) of categorical data and standardized
      mean differences (SMD) of continuous variables were calculated using a random
      effects model. RESULTS: We included 10 RCTs with 3046 participants. Median study
      duration was 6 weeks (range 4-12 weeks). Five studies compared tramadol with
      nonsteroidal anti-inflammatory drugs (NSAIDs) in osteoarthritis pain and one
      trial compared tramadol to flupirtine in low back pain. Morphine was compared to
      antidepressants (two studies), an anticonvulsant (one study) and an
      antiarrhythmic (one study) in different neuropathic pain syndromes. There was no
      significant difference between opioids and nonopioid analgesics in pain reduction
      (SMD 0.03 [95 % confidence interval, CI - 0.18, 0.24]; p = 0.76). Nonopioid
      analgesics were superior to opioids in improving physical function (SMD 0.17 [95
      % CI 0.02, 0.32]; p = 0.03). Patients dropped out due to adverse events more
      frequently with opioids than with nonopioid analgesics (RD 0.09 [95 % CI 0.06,
      0.13]; p < 0.0001). There was no significant difference between opioids and
      nonopioid analgesics in terms of serious adverse events or dropout rates due to
      lack of efficacy. CONCLUSION: Nonopioid analgesics are superior to opioids in
      terms of improvement of physical function and tolerability in short-term (4-12
      weeks) therapy of neuropathic, low back and osteoarthritis pain. Our results do
      not support the concept of an"opioid-requiring" CNCP. The English full-text
      version of this article is freely available at SpringerLink (under
      "Supplemental").

PMID- 25376547
TI  - [Opioids in chronic osteoarthritis pain. A systematic review and meta-analysis of
      efficacy, tolerability and safety in randomized placebo-controlled studies of at
      least 4 weeks duration].
AB  - BACKGROUND: The efficacy, tolerability and safety of opioid therapy in chronic
      osteoarthritis (OA) pain is under debate. We updated a Cochrane systematic review
      on the efficacy and safety of opioids in chronic OA pain published in 2009.
      METHODS: We screened MEDLINE, Scopus and the Cochrane Central Register of
      Controlled Trials (CENTRAL) up until October 2013, as well as reference sections
      of original studies and systematic reviews of randomized controlled trials (RCTs)
      of opioids in chronic osteoarthritis (OA) pain. We included double-blind
      randomized placebo-controlled studies lasting >= 4 weeks. Using a random effects
      model, absolute risk differences (RD) were calculated for categorical data and
      standardized mean differences (SMD) for continuous variables. RESULTS: We
      included 20 RCTs with 33 treatment arms and 8545 participants. Median study
      duration was 12 (4-24) weeks. Oxycodone and tramadol were each tested in six
      studies; buprenorphine, hydromorphone, morphine and tapentadol each in two
      studies and codeine, fentanyl and oxymorphone in one study each. Results are
      reported with 95 % confidence intervals (CIs). Opioids were superior to placebo
      in reducing pain intensity (SMD - 0.22 [- 0.28, - 0.17], p < 0.00001; 16 studies
      with 6743 participants). Opioids were not superior to placebo in 50 % pain
      reduction (RD - 0.00 [- 0.07, 0.07], p = 0.96; two studies with 2684
      participants). Opioids were superior to placebo in terms of reports of much or
      very much global improvement (RD 0.13 [0.05, 0.21], p = 0.002; three studies with
      2251 participants). Opioids were superior to placebo in improving physical
      functioning (SMD - 0.22 [- 0.28, - 0.17], p < 0.00001; 14 studies with 5887
      participants). Patients dropped out more frequently with opioids than with
      placebo (RD 0.17 [0.14, 0.21], p < 0.00001; 15 studies with 6834 participants;
      number needed to harm 5 [4-6]. There was no significant difference between
      opioids and placebo in the frequency of serious adverse events (SAE) or deaths
      over the respective observation periods. CONCLUSION: Opioids were superior to
      placebo in terms of efficacy and inferior in terms of tolerability. The effect
      sizes of average reduction in pain intensity and physical disability were small.
      Opioids and placebo did not differ in terms of safety. The conclusion on the
      safety of opioids compared to placebo is limited by the low number of SAE and
      deaths. Short-term opioid therapy may be considered in selected chronic OA pain
      patients. No current evidence-based guideline recommends opioids as first-line
      treatment option for chronic OA pain. To provide superior evidence for future
      treatment guidelines, RCTs must directly compare existing pharmacological and
      nonpharmacological therapies and administer these in various combinations and
      sequences. The English full-text version of this article is freely available at
      SpringerLink (under "Supplemental").

PMID- 25376548
TI  - [Opioids in chronic neuropathic pain. A systematic review and meta-analysis of
      efficacy, tolerability and safety in randomized placebo-controlled studies of at
      least 4 weeks duration].
AB  - BACKGROUND: The efficacy and safety of opioid therapy in chronic neuropathic pain
      (CNP) is under debate. We updated a recent Cochrane systematic review on the
      efficacy, tolerability and safety of opioids in CNP. METHODS: We screened
      MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL)
      up until October 2013, as well as the reference sections of original studies and
      systematic reviews of randomized controlled trials (RCTs) of opioids in CNP. We
      included double-blind randomized placebo-controlled studies of at least 4 weeks
      duration. Using a random effects model, absolute risk differences (RD) were
      calculated for categorical data and standardized mean differences (SMD) for
      continuous variables. RESULTS: We included 12 RCTs with 1192 participants. The
      included diagnostic entities were painful diabetic neuropathy (four studies),
      postherpetic neuralgia (three studies), mixed polyneuropathic pain (two studies),
      and lumbar root, spinal cord injury and postamputation pain (one study each).
      Mean study duration was 6 (4-12) weeks. Four studies tested morphine, three
      studies tramadol, two studies oxycodone and one study tapentadol. These are the
      pooled results of studies with a parallel or cross-over design: opioids were
      superior to placebo in reducing pain intensity (SMD - 0.64 [95 % confidence
      interval, CI - 0.81, - 0.46], p < 0.0001; 11 studies with 1040 participants).
      Opioids were not superior to placebo in 50 % pain reduction (RD 0.16 [95 % CI -
      0.04, 0.35], p = 0.11; one study with 93 participants). Opioids were not superior
      to placebo in reports of much or very much improved pain (RD 0.17 [95 % CI -
      0.01, 0.36], p = 0.07; one study with 53 participants). Opioids were superior to
      placebo in improving physical functioning (SMD - 0.28 [95 % CI - 0.43, - 0.13], p
      < 0.0001; seven studies with 680 participants). Patients dropped out less
      frequently due to lack of efficacy with opioids than with placebo (RD - 0.07 [95
      % CI - 0.13, - 0.02], p = 0.008; six studies with 656 participants). Patients
      dropped out due to adverse events more frequently with opioids than with placebo
      (RD 0.08 [95 % CI 0.05, 0.12], p < 0.0001; ten studies with 1018 participants;
      number needed to harm 11 [95 % CI 8-17]). There was no significant difference
      between opioids and placebo in terms of the frequency of serious adverse events
      (SAE) or deaths. CONCLUSION: In short-term studies (4-12 weeks) in CNP, opioids
      were superior to placebo in terms of efficacy and inferior in terms of
      tolerability. Opioids and placebo did not differ in terms of safety. The
      conclusion relating to the safety of opioids compared to placebo in CNP is
      limited by the low number of SAE and deaths. Short-term opioid therapy may be
      considered in selected CNP patients. The English full-text version of this
      article is freely available at SpringerLink (under "Supplementary Material").

PMID- 25376549
TI  - Outcomes for adults with type 1 diabetes referred with severe hypoglycaemia
      and/or referred for islet transplantation to a specialist hypoglycaemia service.
AB  - Islet transplantation alone (ITA) is indicated for patients with type 1 diabetes
      (T1D) with disabling severe hypoglycaemia (SH) despite optimised medical therapy.
      We examined outcomes for patients referred to an islet transplant unit with
      recurrent SH. Retrospective case note audit of 45 patients with >=1 SH per year
      who were referred to our ITA unit between 2009-2012; 36 patients attended follow
      up appointments. The cohort was 52.8% male, mean (+/- SD) age 43.9 (+/- 11.4)
      years, and duration of diabetes 26.5 (+/- 12.9) years. Baseline HbA1c was 8.3%
      (+/- 1.7) (67.2 mmol/mol), median (IQR) frequency of SH was 6.0 (2.0-24.0)
      per/patient/year and 83.3% had impaired awareness of hypoglycaemia (IAH). 80.6%
      of patients were referred from other secondary diabetes services, 22.2% had
      completed structured education, and 30.6% were using continuous subcutaneous
      insulin infusion (CSII). Seventeen patients were optimised with conventional
      therapy; SH reduced from 2.0 (1.5-9.0) to 0.0 (0.0-0.5) episodes/patient/year;
      p<0.001, and there was concurrent improvement in HbA1c (8.1-7.7%; 65.0 vs. 60.7
      mmol/mol; p=0.072). Ten patients were listed for transplantation as they were not
      optimised despite structured education, CSII, and continuous glucose monitoring
      (CGM). The remaining 9 had a reduction in SH [7.0 (4.8-40.5) to 4.0 (2.5-6.3)
      episodes/patient/year; p=0.058] and either left the service (n=5) or are still
      being optimised (n=4). In conclusion, 47.2% of patients presenting with
      problematic hypoglycaemia resolved with optimal medical therapy, with a further
      25% achieving clinically relevant improvement, however 27.8% required
      transplantation despite access to all therapies. Provision of expertise in
      hypoglycaemia management is essential to focus limited transplant resources on
      those who need it most.

PMID- 25376550
TI  - Early effects of liver regeneration on endocrine pancreas: in vivo change in
      islet morphology and in vitro assessment of systemic effects on beta-cell
      function and viability in the rat model of two-thirds hepatectomy.
AB  - Liver and pancreas share key roles in glucose homeostasis. Liver regeneration is
      associated with systemic modifications and depends especially on pancreatic
      hormones. The aim of the study was to investigate the role of systemic factors
      released after two-thirds hepatectomy (2/3H) on early possible consequences of
      liver regeneration on endocrine pancreas structure and function. The pancreas and
      serum were harvested 1, 2, or 3 days after 2/3H or sham operation in Lewis rats.
      The HGF and VEGF serum concentrations and plasma microparticles levels were
      measured. The fate of endocrine pancreas was examined through islets
      histomorphometry and function in sham and 2/3H rats. beta-Cell line RIN-m5F
      viability was assessed after 24 h of growth in media supplemented with 10% serum
      from 2/3H or sham rats instead of FCS. Three days after surgery, the pancreas was
      heavier in 2/3H compared to sham rats (0.56 vs. 0.40% of body weight, p < 0.05)
      and the proportion of islets of intermediate size was lower in 2/3H rats (5 vs.
      15%, p < 0.05). Compared to Sham, sera obtained 3 days after hepatectomy were
      more efficient to maintain the viability of RIN-m5F cells (99 vs. 67%, p < 0.01).
      Three days after surgery, no significant differences in serum HGF, a trend to
      significant increase in VEGF concentration and a significant increase in
      microparticles levels, were observed in 2/3H vs. sham rats (9.8 vs. 6.5 nM Phtd
      Ser Eq., p < 0.05). Liver regeneration is associated with early effects on islets
      and could influence beta-cell viability and function by systemic effect.

PMID- 25376553
TI  - Interpreting diagnostic tests in ESRD patients: an introduction.

PMID- 25376551
TI  - Mutual modulation between norepinephrine and nitric oxide in haemocytes during
      the mollusc immune response.
AB  - Nitric oxide (NO) is one of the most important immune molecules in innate
      immunity of invertebrates, and it can be regulated by norepinephrine in ascidian
      haemocytes. In the present study, the mutual modulation and underlying mechanism
      between norepinephrine and NO were explored in haemocytes of the scallop Chlamys
      farreri. After lipopolysaccharide stimulation, NO production increased to a
      significant level at 24 h, and norepinephrine concentration rose to remarkable
      levels at 3 h and 12~48 h. A significant decrease of NO production was observed
      in the haemocytes concomitantly stimulated with lipopolysaccharide and alpha
      adrenoceptor agonist, while a dramatic increase of NO production was observed in
      the haemocytes incubated with lipopolysaccharide and beta-adrenoceptor agonist.
      Meanwhile, the concentration of cyclic adenosine monophosphate (cAMP) decreased
      significantly in the haemocytes treated by lipopolysaccharide and alpha/beta
      adrenoceptor agonist, while the content of Ca(2+) was elevated in those triggered
      by lipopolysaccharide and beta-adrenoceptor agonist. When the haemocytes was
      incubated with NO donor, norepinephrine concentration was significantly enhanced
      during 1~24 h. Collectively, these results suggested that norepinephrine exerted
      varied effects on NO production at different immune stages via a novel alpha/beta
      adrenoceptor-cAMP/Ca(2+) regulatory pattern, and NO might have a feedback effect
      on the synthesis of norepinephrine in the scallop haemocytes.

PMID- 25376552
TI  - Reduced CD5(+) CD24(hi) CD38(hi) and interleukin-10(+) regulatory B cells in
      active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit
      increased circulating autoantibodies.
AB  - Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated
      vasculitis is B cell-dependent, although how particular B cell subsets modulate
      immunopathogenesis remains unknown. Although their phenotype remains
      controversial, regulatory B cells (Bregs ), play a role in immunological
      tolerance via interleukin (IL)-10. Putative CD19(+) CD24(hi) CD38(hi) and CD19(+)
      CD24(hi) CD27(+) Bregs were evaluated in addition to their CD5(+) subsets in 69
      patients with ANCA-associated vasculitis (AAV). B cell IL-10 was verified by flow
      cytometry following culture with CD40 ligand and cytosine-phosphate-guanosine
      (CpG) DNA. Patients with active disease had decreased levels of CD5(+) CD24(hi)
      CD38(hi) B cells and IL-10(+) B cells compared to patients in remission and
      healthy controls (HCs). As IL-10(+) and CD5(+) CD24(hi) CD38(hi) B cells
      normalized in remission within an individual, ANCA titres decreased. The CD5(+)
      subset of CD24(hi) CD38(hi) B cells decreases in active disease and rebounds
      during remission similarly to IL-10-producing B cells. Moreover, CD5(+) B cells
      are enriched in the ability to produce IL-10 compared to CD5(neg) B cells.
      Together these results suggest that CD5 may identify functional IL-10-producing
      Bregs . The malfunction of Bregs during active disease due to reduced IL-10
      expression may thus permit ANCA production. 

PMID- 25376556
TI  - Exceeding DOQI A-V fistula target at the northwest renal network 16: Is 80-90% A
      V fistula rate achievable?

PMID- 25376557
TI  - Republicans take control of Senate, though repeal of Obamacare is unlikely.

PMID- 25376558
TI  - Attitude of epilepsy patients and their attendants for participating in research
      on status epilepticus.
AB  - To evaluate the reason joining in status epilepticus (SE) trial by epilepsy
      patients and attendants and their preferences for types of trials and consent.
      The participants were interviewed after giving a SE case summary. Their
      demographic details, reason of consenting or non-consenting and preference of
      trials and type of consent were noted. The responses of the patients and
      attendants were compared. 77 subjects participated and 47 (61 %) were willing to
      participate in the trial mainly due to self-interest (treatment by specialist,
      best treatment and treatment availability only by trial). The reasons for
      unwilling were apprehension and lack of will. The participants preferred a head
      to-head trial over a placebo-controlled (21 vs. 3), proxy consent rather than
      waived consent (16 vs. 6) and preconsent (16 vs. 3). These responses were not
      different between patients and attendants. 61 % subjects were willing to
      participate in SE trial especially in head-to-head trial with proxy consent.

PMID- 25376560
TI  - Differential expression of microRNAs and their target genes in non-small-cell
      lung cancer.
AB  - MicroRNAs (miRNAs) are single-stranded RNA species that constitute a class of non
      coding RNAs, and are emerging as key regulators of gene expression. Since each
      miRNA is capable of regulating multiple genes, miRNAs are attractive markers for
      studies of coordinated gene expression. In this study, we investigated miRNA
      expression profiling using a massively parallel sequencing technique to compare
      non-small-cell lung cancer (NSCLC) tissue and normal lung tissue. Lung cancer
      tissue and normal lung tissue were obtained from nine NSCLC patients. RNA
      isolated from these samples was processed using RNA sequencing (RNA Seq) and the
      HiSeq 2000 system. Differentially expressed miRNAs and mRNAs were analyzed using
      a t-test. We selected target pairs that showed a negative correlation among
      significantly differentially expressed miRNAs and their putative target mRNAs
      using miRBase Targets. The differences in the expression levels of 222 miRNAs and
      1,597 genes were statistically significant, as indicated by an absolute fold
      change >=1.5 and P<0.05. miR-577, miR-301b, miR-944, miR-891a and miR-615-3p were
      generally upregulated, and miR-338-3p was generally downregulated. miRNA-mRNA
      target pair analysis revealed that 49 miRNAs had 696 target mRNAs. There were
      significantly differentially expressed miRNAs and mRNAs between lung cancer and
      normal tissue. Further investigation of miRNAs and their target genes is
      warranted to better understand NSCLC.

PMID- 25376561
TI  - Nonlocal modeling of granular flows down inclines.
AB  - Flows of granular media down a rough inclined plane demonstrate a number of
      nonlocal phenomena. We apply the recently proposed nonlocal granular fluidity
      model to this geometry and find that the model captures many of these effects.
      Utilizing the model's dynamical form, we obtain a formula for the critical
      stopping height of a layer of grains on an inclined surface. Using an existing
      parameter calibration for glass beads, the theoretical result compares
      quantitatively to existing experimental data for glass beads. This provides a
      stringent test of the model, whose previous validations focused on driven steady
      flow problems. For layers thicker than the stopping height, the theoretical flow
      profiles display a thickness-dependent shape whose features are in agreement with
      previous discrete particle simulations. We also address the issue of the Froude
      number of the flows, which has been shown experimentally to collapse as a
      function of the ratio of layer thickness to stopping height. While the collapse
      is not obvious, two explanations emerge leading to a revisiting of the history of
      inertial rheology, which the nonlocal model references for its homogeneous flow
      response. 

PMID- 25376559
TI  - The heterogeneity of non-motor symptoms of Parkinson's disease.
AB  - In addition to motor symptoms, patients with Parkinson's disease (PD) may
      experience non-motor symptoms (NMS), more often with more advanced disease stage.
      However, the clinical feature of the NMS and potential risk factors that affect
      NMS in idiopathic PD patients remain unclear. 493 PD patients diagnosed with PD
      via the UK. Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria
      and 93 healthy control subjects (CN) were recruited in the current study.
      Questionnaires were used to assess the NMS, motor symptoms, cognitive function,
      and disease severity in both groups. Levodopa daily dose was calculated in PD
      patients. Multivariate linear regression analysis was used to identify the risk
      factors that potentially affect NMS in PD patients. The results showed that, the
      NMS occurrence and positive endorsement rate of PD patients were significantly
      higher compared to CN subjects. Multiple stepwise regression analysis found the
      motor symptom was the only factor that affected NMS in PD patients within five
      years of the disease course, whereas motor symptoms, cognitive function, disease
      severity and Levodopa daily dose significantly affected NMS if the disease course
      was more than five years. These findings demonstrated that NMS are affected by
      several risk factors at different stages of PD. The distribution of difference
      NMS is associated with the severity of motor symptoms and the dosage of anti-PD
      medications in Chinese PD patients. 

PMID- 25376562
TI  - Few benefits, likely harms: against universal random urine drug screening in pain
      management.

PMID- 25376564
TI  - Background knowledge in the early days.
AB  - The purpose of this chapter is to outline the medical facilities that were
      available to the inventors of radiosurgery at the time when the technique was
      being developed. This is achieved by describing in brief the timeline of
      discoveries relevant to clinical neurology and the investigation of neurological
      diseases. This provides a background understanding for the limitations inherent
      in the early days when investigations and imaging in particular were fairly
      primitive. It also helps to explain the choices that were made by the pioneers in
      those early days. The limitations of operative procedures and institutions
      designed to treat neurological diseases are also mentioned. 

PMID- 25376565
TI  - Some physics from 550 BC to AD 1948.
AB  - This chapter outlines terminology and its origins. It traces the development of
      physics ideas from Thales of Miletus, via Isaac Newton, to the nuclear physics
      investigations at the beginning of the twentieth century. It also outlines the
      evolving technology required to make the discoveries that would form the basis of
      radiosurgery. Up to the 1920s, all experiments on atomic structure and
      radioactivity had involved the use of vacuum tubes and naturally occurring
      radioactive substances. There was a need to make useable subatomic particles to
      obtain better understanding of the interior structure of atoms. Because of this,
      machines that could make atoms move at high speed were invented, known as
      particle accelerators. A new era had dawned. There is a brief mention of the
      effect of radiation on living tissue and of the units used to measure it. 

PMID- 25376563
TI  - Pathomechanisms in heart failure: the contractile connection.
AB  - Heart failure is a multi-factorial progressive disease in which eventually the
      contractile performance of the heart is insufficient to meet the demands of the
      body, even at rest. A distinction can be made on the basis of the cause of the
      disease in genetic and acquired heart failure and at the functional level between
      systolic and diastolic heart failure. Here the basic determinants of contractile
      function of myocardial cells will be reviewed and an attempt will be made to
      elucidate their role in the development of heart failure. The following topics
      are addressed: the tension generating capacity, passive tension, the rate of
      tension development, the rate of ATP utilisation, calcium sensitivity of tension
      development, phosphorylation of contractile proteins, length dependent activation
      and stretch activation. The reduction in contractile performance during systole
      can be attributed predominantly to a loss of cardiomyocytes (necrosis), myocyte
      disarray and a decrease in myofibrillar density all resulting in a reduction in
      the tension generating capacity and likely also to a mismatch between energy
      supply and demand of the myocardium. This leads to a decline in the ejection
      fraction of the heart. Diastolic dysfunction can be attributed to fibrosis and an
      increase in titin stiffness which result in an increase in stiffness of the
      ventricular wall and hampers the filling of the heart with blood during diastole.
      A large number of post translation modifications of regulatory sarcomeric
      proteins influence myocardial function by altering calcium sensitivity of tension
      development. It is still unclear whether in concert these influences are adaptive
      or maladaptive during the disease process. 

PMID- 25376566
TI  - Medical physics--particle accelerators--the beginning.
AB  - This chapter outlines the early development of particle accelerators with the
      redesign from linear accelerator to cyclotron by Ernest Lawrence with a view to
      reducing the size of the machines as the power increased. There are
      minibiographies of Ernest Lawrence and his brother John. The concept of
      artificial radiation is outlined and the early attempts at patient treatment are
      mentioned. The reasons for trying and abandoning neutron therapy are discussed,
      and the early use of protons is described. 

PMID- 25376567
TI  - From particle accelerator to radiosurgery.
AB  - This chapter outlines the requirements for machines that could perform
      radiosurgery. It also outlines the characteristics of the narrow beams used for
      this method. The reasons for limiting human treatments to the pituitary fossa are
      justified. The experiments, the results of which determined what was possible
      clinically, are outlined. The two methods of delivery of focused radiation are
      discussed: Bragg peak and beam crossover. 

PMID- 25376569
TI  - Stereotactic and radiosurgery research in Sweden.
AB  - This chapter starts with some comments upon the man who after Leksell was most
      instrumental in developing the Gamma Knife, the physicist Borje Larsson.
      Radiobiology experiments were carried out on rabbits and goats to determine and
      quantify the effects of focused fine beam radiation on the brain. The aim was to
      destroy the normal brain with a view to treating functional disease in the brain
      using focused radiation. The results in a few early patients are mentioned. The
      reasons for dissatisfaction with proton radiosurgery are presented. 

PMID- 25376568
TI  - Stereotactic and radiosurgery concepts in Sweden.
AB  - This chapter mentions again the requirements for a radiosurgery delivery system.
      There is a brief biography of the Swedish neurosurgeon Lars Leksell. Leksell's
      stereotactic frame and system is outlined. In 1951, Leksell wrote a seminal paper
      on radiosurgery that was a statement of concepts, all of which were remarkably
      well understood. The first cases treated with an available industrial X-ray
      machine are recounted. These early cases were successful enough to stimulate
      further efforts to improve the method. 

PMID- 25376570
TI  - The journey from proton to gamma knife.
AB  - It was generally accepted by the early 1960s that proton beam radiosurgery was
      too complex and impractical. The need was seen for a new machine. The beam design
      had to be as good as a proton beam. It was also decided that a static design was
      preferable even if the evolution of that notion is no longer clear. Complex
      collimators were designed that using sources of cobalt-60 could produce beams
      with characteristics adequately close to those of proton beams. The geometry of
      the machine was determined including the distance of the sources from the patient
      the optimal distance between the sources. The first gamma unit was built with
      private money with no contribution from the Swedish state, which nonetheless
      required detailed design information in order to ensure radiation safety. This
      original machine was built with rectangular collimators to produce lesions for
      thalamotomy for functional work. However, with the introduction of dopamine
      analogs, this indication virtually disappeared overnight. 

PMID- 25376571
TI  - The earliest gamma unit patients.
AB  - The inventors were very excited and drove the first patient from Stockholm over
      100 km for the first treatment. The treatment was a technical success. The new
      machine was transported to Sophiahemmet (a private Stockholm hospital) and
      installed. A further eight patients were treated and assessed. At the start,
      there was no computerized treatment planning program, but this was soon developed
      and named KULA after the Swedish word for a sphere, since the actual treatment
      unit was spherical. The term Gamma Knife was first used later by the Pittsburgh
      group.

PMID- 25376572
TI  - Stockholm radiosurgery developing 1968-1982.
AB  - For 14 years, Stockholm was the only location where a gamma unit was in use.
      During this period, a variety of indications were treated. The original machine
      had been designed with a view to treating functional disease. This was
      impractical as new medicines had tried up the referrals. So, the machine was used
      for certain tumors and vascular lesions. A new gamma unit was made this time with
      round collimators more suited to the task in hand. All in all, 762 patients were
      treated during this time with 209 vascular, 342 tumor, and 177 functional
      indications. There were also 34 diverse cases. All these cases were treated
      before the introduction of computerized imaging. 

PMID- 25376574
TI  - Changing times and early debates.
AB  - The machine was soon being called the Gamma Knife. Its spread led to increasing
      numbers of papers from different centers but particularly Pittsburgh. As
      mentioned in the preface, the introduction of new methods in medicine is seldom
      without problems. There were a number of squabbles about the treatment of various
      indications. It was suggested that for AVMs, the GKS was unnecessary. For
      meningiomas, there was marked skepticism within the milieu itself in the early
      days. Metastases were not treated in Stockholm because of Leksell's opposition to
      the treatment of malignant disease, and indeed, these tumors became generally
      popular indications rather later. There was a thought that pituitary adenomas
      could be better treated with GKS but it proved too unreliable, and for these
      tumors, GKS remains an ancillary treatment method. The most marked disagreements
      were with respect of the vestibular schwannomas. This discussion continues to the
      present. 

PMID- 25376573
TI  - From Stockholm to Pittsburgh.
AB  - Leksell's conservatism led him to underestimate the demand for new gamma units.
      When two of his students wanted machines in, respectively, Buenos Aires and
      Sheffield, there was no possibility for manufacture in Sweden. Arrangements were
      made for a Swiss company to make two machines that were installed in the two
      centers but not without problems. Eventually, since the demand was there,
      arrangements were made to continue manufacture in Sweden by Elekta, the company
      that still makes them today. When these matters were settled, the first US model
      was installed in Pittsburgh. This became a crucial development, not only because
      the machine was now established in the United States but also because of the
      quality of the publishing from Pittsburgh, which was of the highest quality,
      honest and believable, and thus a potent impulse in the spread of Gamma Knife
      treatment. 

PMID- 25376575
TI  - The development of dose planning.
AB  - In the very earliest days, there was no computerized dose-planning system.
      However, it was not long that the first dose-planning system KULA was developed
      in the mid-1980s. It soon became apparent that while this was geometrically
      accurate, it was not as visually attractive as programs used by other
      technologies. It had been designed in the era prior to computerized imaging and
      had only limited capacity for dosimetry. It was followed by GammaPlan, which has
      evolved over the years into a sophisticated multiparameter system with very
      advanced graphic features.

PMID- 25376576
TI  - Changing the gamma knife.
AB  - The first Gamma Knife used helmets containing collimators of different diameters
      that increase the flexibility of the treatment. Changing these helmets was time
      consuming and tedious. The original model that was introduced into the United
      States was the U model where the patient was inserted into the machine inward and
      upward, using hydraulics. A new simpler machine was devised called the B model
      where the patient simply moved in and out, but there was still the problem of
      changing helmets. Then, the C model was introduced, with a robot called the
      automatic positioning system that permitted the patient's position to be moved
      automatically. However, the helmets still had to be changed when collimators of
      different sizes were required. Finally, an entirely redesigned model called
      Perfexion was introduced where there were no helmets and the patient once placed
      in the machine would be treated completely following a single pressure on a
      button.

PMID- 25376577
TI  - Conclusion and possible future trends.
AB  - No technology will continue unchanged indefinitely. The Gamma Knife Perfexion
      sets a gold standard today, but at some unspecified future date, new ideas will
      emerge, though none seem to be likely in the short term. The treatment of
      neurosurgical conditions today cannot be sensibly undertaken by single
      practitioners. Teams, consisting of members with the appropriate expertise, are
      required to meet and discuss and agree on patient treatment that is then
      allocated to one or other members of the group. Conflicts will always arise but
      their effects can be minimized by the use of treatment teams and awareness of
      past conflicts and their speedy discharge into wastebasket of medical amnesia. 

PMID- 25376578
TI  - The history of the gamma knife. Preface.

PMID- 25376580
TI  - Biomarkers in the pharmaceutical industry.

PMID- 25376581
TI  - The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human
      saliva.
AB  - BACKGROUND: Extracellular RNAs (exRNAs) in human body fluids are emerging as
      effective biomarkers for detection of diseases. Saliva, as the most accessible
      and noninvasive body fluid, has been shown to harbor exRNA biomarkers for several
      human diseases. However, the entire spectrum of exRNA from saliva has not been
      fully characterized. METHODS: Using high-throughput RNA sequencing (RNA-Seq), we
      conducted an in-depth bioinformatic analysis of noncoding RNAs (ncRNAs) in human
      cell-free saliva (CFS) from healthy individuals, with a focus on microRNAs
      (miRNAs), piwi-interacting RNAs (piRNAs), and circular RNAs (circRNAs). RESULTS:
      Our data demonstrated robust reproducibility of miRNA and piRNA profiles across
      individuals. Furthermore, individual variability of these salivary RNA species
      was highly similar to those in other body fluids or cellular samples, despite the
      direct exposure of saliva to environmental impacts. By comparative analysis of
      >90 RNA-Seq data sets of different origins, we observed that piRNAs were
      surprisingly abundant in CFS compared with other body fluid or intracellular
      samples, with expression levels in CFS comparable to those found in embryonic
      stem cells and skin cells. Conversely, miRNA expression profiles in CFS were
      highly similar to those in serum and cerebrospinal fluid. Using a customized
      bioinformatics method, we identified >400 circRNAs in CFS. These data represent
      the first global characterization and experimental validation of circRNAs in any
      type of extracellular body fluid. CONCLUSIONS: Our study provides a comprehensive
      landscape of ncRNA species in human saliva that will facilitate further biomarker
      discoveries and lay a foundation for future studies related to ncRNAs in human
      saliva.

PMID- 25376583
TI  - Care and prudence as main directive in clinical research on neurosurgical
      intervention for schizophrenia.

PMID- 25376582
TI  - Noninvasive prenatal testing for Wilson disease by use of circulating single
      molecule amplification and resequencing technology (cSMART).
AB  - BACKGROUND: Noninvasive prenatal testing (NIPT) for monogenic diseases by use of
      PCR-based strategies requires precise quantification of mutant fetal alleles
      circulating in the maternal plasma. The study describes the development and
      validation of a novel assay termed circulating single-molecule amplification and
      resequencing technology (cSMART) for counting single allelic molecules in plasma.
      Here we demonstrate the suitability of cSMART for NIPT, with Wilson Disease (WD)
      as proof of concept. METHODS: We used Sanger and whole-exome sequencing to
      identify familial ATP7B (ATPase, Cu(++) transporting, beta polypeptide) gene
      mutations. For cSMART, single molecules were tagged with unique barcodes and
      circularized, and alleles were targeted and replicated by inverse PCR. The unique
      single allelic molecules were identified by sequencing and counted, and the
      percentage of mutant alleles in the original maternal plasma sample was used to
      determine fetal genotypes. RESULTS: Four families with WD pedigrees consented to
      the study. Using Sanger and whole-exome sequencing, we mapped the pathogenic
      ATP7B mutations in each pedigree and confirmed the proband's original diagnosis
      of WD. After validation of cSMART with defined plasma models mimicking fetal
      inheritance of paternal, maternal, or both parental mutant alleles, we
      retrospectively showed in second pregnancies that the fetal genotypes assigned by
      invasive testing and NIPT were concordant. CONCLUSIONS: We developed a reliable
      and accurate NIPT assay that correctly diagnosed the fetal genotypes in 4
      pregnancies at risk for WD. This novel technology has potential as a universal
      strategy for NIPT of other monogenic disorders, since it requires only knowledge
      of the parental pathogenic mutations.

PMID- 25376584
TI  - Genetic variants of pulmonary SP-D predict disease outcome of COPD in a Chinese
      population.
AB  - BACKGROUND AND OBJECTIVE: Although surfactant protein-D (SP-D) has been suggested
      as a biomarker for chronic obstructive pulmonary disease (COPD), the relationship
      between genetic variants of SP-D and disease outcome of COPD remains unknown. We
      hypothesized that genetic polymorphisms of SP-D are associated with COPD-related
      phenotypes and disease prognosis. METHODS: A hospital-based, case-controlled
      study was conducted prospectively. Six single nucleotide polymorphisms of the
      SFTPD gene were determined for genetic association analysis. Inflammatory
      cytokines and SP-D serum level were quantified. Frequency of exacerbation and
      change of lung function were assessed. All-cause 3-year mortality was registered.
      RESULTS: We studied 320 smokers (192 with COPD and 128 at-risk for COPD) who were
      prospectively monitored for at least 3 years. The serum levels of SP-D in COPD
      patients were significantly associated with the degree of airflow obstruction and
      frequency of exacerbation. Haplotype association analysis revealed that haplotype
      G-G-C-C-A was associated with lower risk of COPD (P = 0.03) in our study
      population. COPD patients with haplotype G-G-C-C-A had lower serum SP-D levels (P
      < 0.001), higher rates of positive response to bronchodilator treatment (P =
      0.01), more improvement of forced expiratory volume in 1 s in yearly follow-up (P
      = 0.03) and better 3-year survival rate than COPD patients with non G-G-C-C-A
      haplotype (P = 0.03). CONCLUSIONS: Genetic haplotype of SP-D may serve as a
      valuable prognostic indicator in Chinese patients with COPD.

PMID- 25376585
TI  - Pulsed dye laser therapy for infantile hemangiomas: a systemic review and meta
      analysis.
AB  - BACKGROUND: Infantile hemangiomas (IH) are common pediatric tumors. This meta
      analysis was performed to review the therapeutic efficacy and safety of pulsed
      dye laser (PDL) in the treatment of IH. METHODS: Seven databases were searched,
      including PubMed, OvidSP, Karger, Elsevier, EMBASE, Web of Science and Wiley
      Online Library. The review collected the characteristics of year of publication,
      hemangiomas cases, prior treatment, laser parameters, adverse side, pretreatment
      symptom, and number of response from all articles. RESULTS: A total of 1580
      studies were identified, the first round search retrieved 39 articles met
      inclusion criteria. Of those, only 13 articles with 1529 hemangiomas were
      included in the meta-analysis. This meta-analysis demonstrated an overall
      resolution rate of 89.1% with 6.28% incidence of adverse effect. CONCLUSION: PDL
      may be the effective modality to decrease the proliferative phase and accelerate
      rates of involution and resolution with few adverse events.

PMID- 25376586
TI  - A need for tetanus vaccination before restoration activities in Fukushima, Japan.

PMID- 25376587
TI  - The effects of dietary polyphenols on reproductive health and early development.
AB  - BACKGROUND: Emerging evidence from clinical and epidemiological studies suggests
      that dietary polyphenols play an important role in the prevention of chronic
      diseases, including cancer, cardiovascular disease, diabetes and
      neurodegenerative disorders. Although these beneficial health claims are
      supported by experimental data for many subpopulation groups, some studies
      purport that excessive polyphenol consumption may have negative health effects in
      other subpopulations. The ever-growing interest and public awareness surrounding
      the potential benefits of natural health products and polyphenols, in addition to
      their widespread availability and accessibility through nutritional supplements
      and fortified foods, has led to increased consumption throughout gestation.
      Therefore, understanding the implications of polyphenol intake on obstetrical
      health outcomes is of utmost importance with respect to safe consumption during
      pregnancy. METHODS: Using relevant keywords, a literature search was performed to
      gather information regarding polyphenol pharmacology and the molecular mechanisms
      by which polyphenols exert their biological effects. The primary focus of this
      paper is to understand the relevance of these findings in the context of
      reproductive physiology and medicine. RESULTS: Evidence from both in vitro
      experiments and in vivo studies using animals and humans demonstrates that
      polyphenols regulate key targets related to oxidative stress, inflammation and
      advanced glycation end products. Although the majority of these studies have been
      conducted in the context of chronic diseases, such as cancer and diabetes,
      several of the key targets influenced by polyphenols are also related to a
      variety of obstetrical complications, including pre-eclampsia, intrauterine
      growth restriction and preterm birth. Polyphenols have also been shown to
      influence fertility and sexual development, fetal health and the bioavailability
      of nutrients. CONCLUSIONS: Further research leading to a thorough understanding
      of the physiological roles and potential clinical value that polyphenol
      consumption may play in pregnancy is urgently needed to help inform patient
      safety.

PMID- 25376588
TI  - Are Informant Reports of Personality More Internally Consistent Than Self Reports
      of Personality?
AB  - The present study examined whether informant-reported personality was more or
      less internally consistent than self-reported personality in an epidemiological
      community sample (n = 1,449). Results indicated that across the 5 NEO
      (Neuroticism-Extraversion-Openness) personality factors and the 10 personality
      disorder trait dimensions, informant reports tended to be more internally
      consistent than self reports, as indicated by equal or higher Cronbach's alpha
      scores and higher average interitem correlations. In addition, the informant
      reports collectively outperformed the self reports for predicting responses on a
      global measure of health, indicating that the informant reports are not only more
      reliable than self reports, but they can also be useful in predicting an external
      criterion. Collectively these findings indicate that informant reports tend to
      have greater internal consistency than self reports. 

PMID- 25376590
TI  - Malaria prevention measures in Burkina Faso: distribution and households
      expenditures.
AB  - BACKGROUND: The provision of insecticide-treated nets (ITNs) is widely accepted
      in Burkina Faso thanks to large-scale national distribution campaigns. However,
      household also use other methods of prevention. Thus far, there is little
      knowledge about the expenditures of these malaria prevention methods,
      particularly in combination with the national interventions. This paper presents
      the utilization levels and expenditures of malaria prevention tools in Burkina
      Faso and explores the potential inequality in ownership. METHODS: The analysis is
      based on a cross-sectional survey, conducted during the 2010 high transmission
      season from July to September in the Nanoro Health and Demographic Surveillance
      Site. Following a systematic sampling technique, the survey covers 500 households
      with children under 5 years of age from 24 villages. In the survey, households
      were asked about expenditures on malaria prevention methods in the month
      preceding the survey. This includes expenditure on coils, indoor spraying,
      aerosols, repellents, herbs, cleaning of the environment and clearing of the
      vegetation. The data analysis was conducted with SPSS taking into account the
      socio-economic status (SES) of the household to examine any differences in the
      utilization of the prevention method and expenditure quintiles. An asset-based
      index, created through principal components analysis (PCA), was used to
      categorize the households into quintiles. FINDINGS: Of the households surveyed,
      45% used one preventive measure in the past month; 29% used two measures; and 25%
      used three or more measures. A significant association was found between the
      number of prevention measures and the SES of the household (p < 0.05). The
      majority of households owned at least one insecticide treated net (ITN) (98%).
      Among households that used ITN, 53.8% used methods other than bed nets. The
      majority of households paid nothing for malaria prevention. CONCLUSION: Most of
      the households received bed nets and other preventive method for free. There is
      equity in expenditures across SES groups. Free distribution of ITNs ensured that
      there was equity in ITN ownership among households. More research on the
      possibility of increasing access to other locally relevant methods of malaria
      control that proved to be effective is need.

PMID- 25376593
TI  - WITHDRAWN: Is it "science"... or is it "turf" guarding?
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25376591
TI  - Partial hepatectomy for liver metastases from nasopharyngeal carcinoma: a
      comparative study and review of the literature.
AB  - BACKGROUND: The management of liver metastases from nasopharyngeal carcinoma
      (NPC) has not been extensively investigated. This study aimed to compare the long
      term outcome of patients with liver metastases from NPC who were treated by a
      partial hepatectomy or transcatheter hepatic artery chemoembolization (TACE).
      METHODS: Between January 1993 and December 2010, 830 patients were diagnosed with
      liver metastases from NPC and exhibited a complete response to the primary cancer
      of the nasopharynx and regional lymph nodes. Fifteen patients with intrahepatic
      metastasis underwent R0 partial hepatectomy. As a parallel control group, another
      15 patients with a resectable liver metastasis who underwent TACE were selected.
      Prior to the resection and TACE that were performed on patients in these two
      groups, radical radiotherapy with or without adjuvant chemotherapy was
      administered. Clinicopathological data and treatment outcomes were compared
      retrospectively. RESULTS: No significant differences were observed between the
      two groups in terms of the clinicopathological features, which include gender
      ratio, liver function, accompanying cirrhosis, rate of infection with the
      hepatitis B virus, tumor size, tumor number, pathological type and preoperative
      comorbidities. The 1-, 3- and 5-year overall survival rates from the time of
      hepatectomy were 85.7%, 64.2% and 40.2%, respectively, with a median survival of
      45.2 months, whereas the 1-, 3- and 5-year overall survival rates were 53.3%,
      26.6% and 20.0% for patients in the control group (P = 0.039), respectively, with
      a median survival of 14.1 months. The actuarial median progression-free survival
      (PFS) of the patients in the resection group was 21.2 months, and the 1-, 3- and
      5-year PFS rates were 70%, 53% and 18%, respectively. In the control group, the 1
      , 3- and 5-year PFS rates were 27%, 7% and 0.0% (P = 0.007), respectively, with a
      median survival of 4.2 months. Thus far, 5 patients have survived for more than 5
      years, and the longest survival time is 168.1 months. CONCLUSIONS: For patients
      with limited liver metastases from NPC, hepatectomy provides a survival advantage
      over TACE. Due to the limited treatment options for patients with liver
      metastasis from NPC, hepatectomy should be recommended as an optimal treatment.
      Moreover, perioperative chemotherapy may be associated with an improved
      prognosis.

PMID- 25376595
TI  - David N.S. Kerr (1927-2014).

PMID- 25376594
TI  - Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study
      by 3.0-tesla magnetic resonance spectroscopy.
AB  - INTRODUCTION: Previous magnetic resonance spectroscopy (MRS) and mass
      spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in
      mutant isocitrate dehydrogenase (IDH) gliomas. IDH mutation is known to be a
      powerful positive prognostic marker in malignant gliomas. Hence, 2HG accumulation
      in gliomas was assumed to be a positive prognostic factor in gliomas, but this
      has not yet been proven. Here, we analyzed 52 patients harboring World Health
      Organization (WHO) grade II and III gliomas utilizing 3.0-tesla MRS. RESULTS:
      Mutant IDH gliomas showed significantly higher accumulation of 2HG (median 5.077
      vs. 0.000, p =0.0002, Mann-Whitney test). 2HG was detectable in all mutant IDH
      gliomas, whereas in 10 out of 27 (37.0%) wild-type IDH gliomas, 2HG was below the
      detectable range (2HG =0) (p =0.0003, chi-squared test). Screening for IDH
      mutation by 2HG analysis was highly sensitive (cutoff 2HG =1.489 mM, sensitivity
      100.0%, specificity 72.2%). Gliomas with high 2HG accumulation had better overall
      survival than gliomas with low 2HG accumulation (p =0.0401, Kaplan-Meier
      analysis). DISCUSSION: 2HG accumulation detected by 3.0-tesla MRS not only
      correlates well with IDH status, but also positively correlates with survival in
      WHO grade II and III gliomas.

PMID- 25376596
TI  - Fabrication of hierarchically porous materials and nanowires through coffee ring
      effect.
AB  - We report a versatile method for the fabrication of nanowires and hierarchical
      porous materials from a wide variety of ceramic materials such as CaCO3, ZnO,
      CuO, Co3O4, Co-doped ZnO, and Ag2O. The method consists of evaporation of CO2
      enriched water microdroplets (diameter ~3 MUm) deposited from an aerosol onto
      heated substrates (T = 120  degrees C). A variety of porous scaffolds with 1-3
      MUm sized pores can be generated by tuning the process conditions. Subsequent
      sintering of the scaffolds is shown to generate nanosized pores in the walls of
      the porous scaffold creating a dual hierarchy of pore sizes (~50 nm and 1-3 MUm).
      We propose a mechanism for the formation of scaffolds based on the coffee-ring
      effect during the evaporation of microdroplets. Ostwald-ripening of CaCO3
      scaffolds prepared without sintering yields scaffold structures consisting of two
      dimensional crystals of CaCO3 that are one unit cell thick. The favorable
      application of CaCO3 scaffolds for the enhancement of bone healing around
      titanium implants with improved biocompatibility is also demonstrated.

PMID- 25376597
TI  - Effectiveness of sternocleidomastoid flap repair for cervical anastomotic leakage
      after esophageal reconstruction.
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate the effectiveness
      of sternocleidomastoid (SCM) flap repair for anastomotic leakage after
      esophagectomy. METHODS: A refractory cutaneous fistula from the gastric stump
      developed in 8 patients with esophageal cancer who underwent esophagogastric
      anastomosis after esophagectomy. All patients underwent SCM flap repair. The
      cutaneous fistula was removed and resutured. The sternal head of the left SCM was
      dissected from the manubrium of the sternum and sutured onto the repaired gastric
      stump. RESULTS: The operative duration was 80-220 min (median, 120 min). The
      amount of intraoperative bleeding ranged from 5 to 182 g (median, 15 g). The
      absence of recurrent anastomotic leakage was confirmed after the SCM flap repair
      in every patient. Oral intake was initiated 7-15 days (median, 10 days) after the
      repair operation without discomfort. CONCLUSIONS: SCM flap repair is an effective
      and minimally invasive treatment method for cervical anastomotic leakage after
      esophageal reconstruction. This method may be considered in patients with
      refractory leakage of the gastric stump after staple anastomosis.

PMID- 25376598
TI  - Metallomic and metalloproteomic strategies in elucidating the molecular
      mechanisms of metallodrugs.
AB  - Metals play a critical role in life processes, and metal-based drugs nowadays
      have been commonly used for therapeutic and diagnostic purposes. However, severe
      side-effects and acquired drug resistance are the major issues needing to be
      resolved prior to more effective metallodrugs being developed, which requires a
      full understanding of the underlying molecular mechanisms. Metallomic and
      metalloproteomic approaches have received growing attention and have been
      implemented in inorganic medicinal chemistry and chemical biology in the endeavor
      to expand our knowledge of the pharmacological profiles, potential targets and
      functional pathways of metallodrugs. This perspective summarizes some recent
      progress in using metallomic and metalloproteomic strategies to elucidate the
      mechanisms of action of representative anticancer and antimicrobial metal-based
      drugs and agents. 

PMID- 25376599
TI  - Selective adhesion and controlled activity of yeast cells on honeycomb-patterned
      polymer films via a microemulsion approach.
AB  - Selective adhesion, growth promotion, proliferation inhibition and in situ
      transformation of Saccharomyces cerevisiae cells have been realized in a limited
      space of honeycomb-patterned polystyrene films prepared through a microemulsion
      method. 

PMID- 25376600
TI  - Biosimilar insulins: a European perspective.
AB  - Biosimilar insulins are likely to enter clinical practice in Europe in the near
      future. It is important that clinicians are familiar with and understand the
      concept of biosimilarity and how a biosimilar drug may differ from its reference
      product. The present article provides an overview of biosimilars, the European
      regulatory requirements for biosimilars and safety issues. It also summarizes the
      current biosimilars approved in Europe and the key clinical issues associated
      with the use of biosimilar insulins. 

PMID- 25376601
TI  - Stereo- and Regioselective Phyllobilane Oxidation in Leaf Homogenates of the
      Peace Lily (Spathiphyllum wallisii): Hypothetical Endogenous Path to Yellow
      Chlorophyll Catabolites.
AB  - Invited for the cover of this issue is the group of Bernhard Krautler at the
      University of Innsbruck, Austria. The image depicts the autumnal "disappearance"
      of chlorophyll and the ensuing rapid formation of colorless phyllobilins. Read
      the full text of the article at 10.1002/chem.201404783.

PMID- 25376602
TI  - Loop formation and self-fasciculation of cortical axon using photonic guidance at
      long working distance.
AB  - The accuracy of axonal pathfinding and the formation of functional neural
      circuitry are crucial for an organism to process, store, and retrieve information
      from internal networks as well as from the environment. Aberrations in axonal
      migration is believed to lead to loop formation and self-fasciculation, which can
      lead to highly dysfunctional neural circuitry and therefore self-avoidance of
      axons is proposed to be the regulatory mechanism for control of synaptogenesis.
      Here, we report the application of a newly developed non-contact optical method
      using a weakly-focused, near infrared laser beam for highly efficient axonal
      guidance, and demonstrate the formation of axonal loops in cortical neurons,
      which demonstrate that cortical neurons can self-fasciculate in contrast to self
      avoidance. The ability of light for axonal nano-loop formation opens up new
      avenues for the construction of complex neural circuitry, and non-invasive
      guidance of neurons at long working distances for restoration of impaired neural
      connections and functions. 

PMID- 25376603
TI  - Mechanical properties of the hyomandibula in four shark species.
AB  - Sharks have cartilaginous elements that support the jaws and are subjected to
      variable loads. The aim of this study was to understand how these elements, the
      hyomandibulae, respond to compressive loads, and to describe the structural level
      mechanical properties of mineralized cartilage. Mechanical stiffness and
      effective Poisson's ratio of the hyomandibular cartilage were measured in four
      species of sharks (white-spotted bamboo, Chiloscyllium plagiosum; spiny dogfish,
      Squalus acanthias; sandbar, Carcharhinus plumbeus; and dusky smoothhound,
      Mustelus canis). The former two are suction feeders, while the latter two are
      bite feeders. The hyomandibulae of suction feeders were expected to be stiffer
      because of the increased loads on their hyomandibulae. Bamboo sharks, as the
      strongest suction feeders, have the stiffest hyomandibula with a stiffness of
      106.12 MPa. The stiffness of spiny dogfish, sandbar sharks, and dusky
      smoothhounds were 41.58, 58.00, and 49.62 MPa, respectively. The proportion of
      the minerals found in the cross-section of the hyomandibula determines the
      elements stiffness. Effective Poisson's ratio was measured at low axial strains
      and was highly variable ranging from 2.3 * 10(-5) to 4.3 * 10(-1). This implies
      that the behavior of the hyomandibulae under load will be very different in
      different species. Furthermore, this wide range of values for the ratio has
      potential implications for modeling techniques, such as finite element modeling,
      which use Poisson's ratio as a fundamental input.

PMID- 25376605
TI  - Development of a silica monolith modified with Fe3O4 nano-particles in
      centrifugal spin column format for the extraction of phosphorylated compounds.
AB  - In this study, citrate-stabilised iron oxide nano-particles (~16 nm) have been
      immobilised on commercial silica monolithic centrifugal spin columns (MonoSpin)
      for the extraction of phosphorylated compounds. Two alternative strategies were
      adopted involving either direct electrostatic attachment to an aminated MonoSpin
      (single-layer method) in the first instance, or the use of a layer-by-layer
      method with poly(diallyldimethylammonium) chloride. Field-emission scanning
      electron spectroscopy and energy-dispersive X-ray spectroscopy was used for
      confirming notably higher coverage of nano-particles using the layer-by-layer
      method (2.49 +/- 0.53 wt%) compared with the single-layer method (0.43 +/- 0.30
      wt%). The modified monolith was used for the selective separation/extraction of
      adenosine monophosphate, adenosine diphosphate and adenosine triphosphate with
      elution using a phosphate buffer. A reversed-phase liquid chromatographic assay
      was used for confirming that adenosine, as a non-phosphorylated control was not
      retained on the modified MonoSpin devices, whereas recovery of 80% for adenosine
      monophosphate, 86% for adenosine diphosphate and 82% for adenosine triphosphate
      was achieved. 

PMID- 25376604
TI  - Assessing the agreement between 3-meter and 6-meter walk tests in 136 community
      dwelling older adults.
AB  - OBJECTIVE: Walking speed is an important marker of functionality that is measured
      over courses of varying lengths, but it is unclear if course length affects
      measured pace. METHOD: A total of 136 older adults completed two consecutive
      trials each of 3-m and 6-m walking courses, the order of which was randomly
      assigned. We calculated concordance correlation coefficients (CCC) and created
      Bland-Altman plots to evaluate the relationship between the two course distances.
      RESULTS: Average walking speed was faster for the 6-m course and the second trial
      of each course. There was high concordance between the first and second trials
      for both the 3-m and 6-m courses. DISCUSSION: The 3- and 6-m courses had
      excellent test-retest reliability and faster walking speed in later than earlier
      trials. Higher concordance between courses for later trials suggests the utility
      of practice trials and adjusting for course length when combining walking speed
      measurements between different course lengths.

PMID- 25376606
TI  - Modeling targeted inhibition of MEK and PI3 kinase in human pancreatic cancer.
AB  - Activating mutations in the KRAS oncogene occur in approximately 90% of
      pancreatic cancers, resulting in aberrant activation of the MAPK and the PI3K
      pathways, driving malignant progression. Significant efforts to develop targeted
      inhibitors of nodes within these pathways are underway and several are currently
      in clinical trials for patients with KRAS-mutant tumors, including patients with
      pancreatic cancer. To model MEK and PI3K inhibition in late-stage pancreatic
      cancer, we conducted preclinical trials with a mutant Kras-driven genetically
      engineered mouse model that faithfully recapitulates human pancreatic ductal
      adenocarcinoma development. Treatment of advanced disease with either a MEK (GDC
      0973) or PI3K inhibitor (GDC-0941) alone showed modest tumor growth inhibition
      and did not significantly enhance overall survival. However, combination of the
      two agents resulted in a significant survival advantage as compared with control
      tumor-bearing mice. To model the clinical scenario, we also evaluated the
      combination of these targeted agents with gemcitabine, the current standard-of
      care chemotherapy for pancreatic cancer. The addition of MEK or PI3K inhibition
      to gemcitabine, or the triple combination regimen, incrementally enhanced overall
      survival as compared with gemcitabine alone. These results are reminiscent of the
      survival advantage conferred in this model and in patients by the combination of
      gemcitabine and erlotinib, an approved therapeutic regimen for advanced
      nonresectable pancreatic cancer. Taken together, these data indicate that
      inhibition of MEK and PI3K alone or in combination with chemotherapy do not
      confer a dramatic improvement as compared with currently available therapies for
      patients with pancreatic cancer.

PMID- 25376607
TI  - Changes in BAI1 and nestin expression are prognostic indicators for survival and
      metastases in breast cancer and provide opportunities for dual targeted
      therapies.
AB  - The 2-year survival rate of patients with breast cancer brain metastases is less
      than 2%. Treatment options for breast cancer brain metastases are limited, and
      there is an unmet need to identify novel therapies for this disease. Brain
      angiogenesis inhibitor 1 (BAI1) is a GPCR involved in tumor angiogenesis,
      invasion, phagocytosis, and synaptogenesis. For the first time, we identify that
      BAI1 expression is significantly reduced in breast cancer and higher expression
      is associated with better patient survival. Nestin is an intermediate filament
      whose expression is upregulated in several cancers. We found that higher Nestin
      expression significantly correlated with breast cancer lung and brain metastases,
      suggesting both BAI1 and Nestin can be therapeutic targets for this disease.
      Here, we demonstrate the ability of an oncolytic virus, 34.5ENVE, to target and
      kill high Nestin-expressing cells and deliver Vstat120 (extracellular fragment of
      BAI1). Finally, we created two orthotopic immune-competent murine models of
      breast cancer brain metastases and demonstrated 34.5ENVE extended the survival of
      immune-competent mice bearing intracranial breast cancer tumors.

PMID- 25376608
TI  - The protein phosphatase 2A inhibitor LB100 sensitizes ovarian carcinoma cells to
      cisplatin-mediated cytotoxicity.
AB  - Despite early positive response to platinum-based chemotherapy, the majority of
      ovarian carcinomas develop resistance and progress to fatal disease. Protein
      phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of
      DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies have
      shown that LB100, a small-molecule inhibitor of PP2A, sensitizes cancer cells to
      radiation-mediated DNA damage. We hypothesized that LB100 could sensitize ovarian
      cancer cells to cisplatin treatment. We performed in vitro studies in SKOV-3,
      OVCAR-8, and PEO1, -4, and -6 ovarian cancer lines to assess cytotoxicity
      potentiation, cell-death mechanism(s), cell-cycle regulation, and DDR signaling.
      In vivo studies were conducted in an intraperitoneal metastatic mouse model using
      SKOV-3/f-Luc cells. LB100 sensitized ovarian carcinoma lines to cisplatin
      mediated cell death. Sensitization via LB100 was mediated by abrogation of cell
      cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint
      correlated with decreased Wee1 expression, increased cdc2 activation, and
      increased mitotic entry (p-histone H3). LB100 also induced constitutive
      hyperphosphorylation of DDR proteins (BRCA1, Chk2, and gammaH2AX), altered the
      chronology and persistence of JNK activation, and modulated the expression of 14
      3-3 binding sites. In vivo, cisplatin sensitization via LB100 significantly
      enhanced tumor growth inhibition and prevented disease progression after
      treatment cessation. Our results suggest that LB100 sensitizes ovarian cancer
      cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell
      cycle checkpoint abrogation.

PMID- 25376611
TI  - Preclinical pharmacokinetics, tolerability, and pharmacodynamics of metuzumab, a
      novel CD147 human-mouse chimeric and glycoengineered antibody.
AB  - Metuzumab is an affinity-optimized and nonfucosylated anti-CD147 human-mouse
      chimeric IgG1 monoclonal antibody with enhanced antibody-dependent cellular
      cytotoxicity (ADCC). The purpose of this study was to characterize the
      pharmacokinetics, safety, and antitumor activities of metuzumab in mouse, rat,
      and monkey. The ADCC activity was assessed by a lactate dehydrogenase release
      assay. The pharmacokinetics of metuzumab were determined in Sprague-Dawley rats
      and in cynomolgus monkeys. Single- and repeat-dose toxicology studies of the i.v.
      administration of high-dose metuzumab were conducted in cynomolgus monkeys. Mice
      bearing human tumor xenografts were used to evaluate the antitumor efficacy of
      metuzumab. The ADCC potency of metuzumab was enhanced compared with the
      nonglycoengineered parental antibody. Metuzumab also effectively inhibited tumor
      growth in A549 and NCI-H520 xenograft models. In the monkey model, the total
      clearance of metuzumab decreased with increasing dose. The nonspecific clearance
      in monkeys was estimated to be 0.53 to 0.92 mL/h/kg. In single- and repeat-dose
      toxicology studies in cynomolgus monkeys, metuzumab did not induce any distinct
      or novel adverse findings and was well tolerated at all tested doses. These
      preclinical safety data facilitated the initiation of an ongoing clinical trial
      of metuzumab for the treatment of non-small cell lung cancer (NSCLC) in China.

PMID- 25376610
TI  - Antitumor activity of the MEK inhibitor TAK-733 against melanoma cell lines and
      patient-derived tumor explants.
AB  - The goal of this study was to investigate the activity of the selective MEK1/2
      inhibitor TAK-733 in both melanoma cell lines and patient-derived melanoma
      xenograft models. In vitro cell proliferation assays using the sulforhodamine B
      assay were conducted to determine TAK-733 potency and melanoma responsiveness. In
      vivo murine modeling with eleven patient-derived melanoma explants evaluated
      daily dosing of TAK-733 at 25 or 10 mg/kg. Immunoblotting was performed to
      evaluate on-target activity and downstream inhibition by TAK-733 in both in vitro
      and in vivo studies. TAK-733 demonstrated broad activity in most melanoma cell
      lines with relative resistance observed at IC50 > 0.1 MUmol/L in vitro. TAK-733
      also exhibited activity in 10 out of 11 patient-derived explants with tumor
      growth inhibition ranging from 0% to 100% (P < 0.001-0.03). Interestingly,
      BRAF(V600E) and NRAS mutational status did not correlate with responsiveness to
      TAK-733. Pharmacodynamically, pERK was suppressed in sensitive cell lines and
      tumor explants, confirming TAK-733-mediated inhibition of MEK1/2, although the
      demonstration of similar effects in the relatively resistant cell lines and tumor
      explants suggests that escape pathways are contributing to melanoma survival and
      proliferation. These data demonstrate that TAK-733 exhibits robust tumor growth
      inhibition and regression against human melanoma cell lines and patient-derived
      xenograft models, suggesting that further clinical development in melanoma is of
      scientific interest. Particularly interesting is the activity in BRAF wild-type
      models, where current approved therapy such as vemurafenib has been reported not
      to be active.

PMID- 25376609
TI  - DeltaNP63alpha transcriptionally activates chemokine receptor 4 (CXCR4)
      expression to regulate breast cancer stem cell activity and chemotaxis.
AB  - DeltaNP63alpha, the predominant TP63 isoform expressed in diverse epithelial
      tissues, including the mammary gland, is required for the preservation of stem
      cells and has been implicated in tumorigenesis and metastasis. Despite data
      characterizing DeltaNP63alpha as a master regulator of stem cell activity,
      identification of the targets underlying these effects is incompletely
      understood. Recently, DeltaNP63alpha was identified as a key regulator in the
      promotion of proinflammatory programs in squamous cell carcinoma of the head and
      neck. Inflammation has been implicated as a potent driver of cancer stem cell
      phenotypes and metastasis. In this study, we sought to identify novel targets of
      DeltaNP63alpha that confer cancer stem cell and prometastatic properties. Data
      presented here identify the gene encoding the chemokine receptor 4 (CXCR4) as a
      transcriptional target of DeltaNP63alpha. Our data indicate that DeltaNP63alpha
      enhances CXCR4 expression in breast cancer cells via its binding at two regions
      within the CXCR4 promoter. The CXCR4 antagonist AMD3100 was used to demonstrate
      that the pro-stem cell activity of DeltaNP63alpha is mediated through its
      regulation of CXCR4. Importantly, we show that DeltaNP63alpha promotes the
      chemotaxis of breast cancer cells towards the CXCR4 ligand SDF1alpha, a process
      implicated in the trafficking of breast cancer cells to sites of metastasis. This
      study highlights CXCR4 as a previously unidentified target of DeltaNP63alpha,
      which plays a significant role in mediating DeltaNP63alpha-dependent stem cell
      activity and chemotaxis toward SDF1alpha. Our findings suggest that
      DeltaNP63alpha regulation of CXCR4 may have strong implications in the regulation
      of cancer stem cells and metastasis.

PMID- 25376612
TI  - Repurposing the antihelmintic mebendazole as a hedgehog inhibitor.
AB  - The hedgehog (Hh) signaling pathway is activated in many types of cancer and
      therefore presents an attractive target for new anticancer agents. Here, we show
      that mebendazole, a benzamidazole with a long history of safe use against
      nematode infestations and hydatid disease, potently inhibited Hh signaling and
      slowed the growth of Hh-driven human medulloblastoma cells at clinically
      attainable concentrations. As an antiparasitic, mebendazole avidly binds nematode
      tubulin and causes inhibition of intestinal microtubule synthesis. In human
      cells, mebendazole suppressed the formation of the primary cilium, a microtubule
      based organelle that functions as a signaling hub for Hh pathway activation. The
      inhibition of Hh signaling by mebendazole was unaffected by mutants in the gene
      that encodes human Smoothened (SMO), which are selectively propagated in cell
      clones that survive treatment with the Hh inhibitor vismodegib. Combination of
      vismodegib and mebendazole resulted in additive Hh signaling inhibition. Because
      mebendazole can be safely administered to adults and children at high doses over
      extended time periods, we propose that mebendazole could be rapidly repurposed
      and clinically tested as a prospective therapeutic agent for many tumors that are
      dependent on Hh signaling.

PMID- 25376613
TI  - Application of room-temperature aprotic and protic ionic liquids for oxidative
      folding of cysteine-rich peptides.
AB  - The oxidation of the conotoxin MU-SIIIA in different ionic liquids was
      investigated, and the results were compared with those obtained in [C2 mim][OAc].
      Conversion of the reduced precursor into the oxidized product was observed in the
      protic ILs methyl- and ethylammonium formate (MAF and EAf, respectively), whereas
      choline dihydrogenphosphate and Ammoeng 110 failed to yield folded peptide.
      However, the quality and yield of the peptide obtained in MAF and EAF were lower
      than in the case of the product from [C2 mim][OAc]. Reaction conditions
      (temperature, water content) also had an impact on peptide conversion. A closer
      look at the activities of MU-SIIIA versions derived from an up-scaled synthesis
      in [C2 mim][OAc] revealed a significant loss of the effect on ion channel NaV 1.4
      relative to the buffer-oxidized peptide, whereas digestion of either MU-SIIIA
      product by trypsin was unaffected. This was attributed to adherence of ions from
      the IL to the peptide, because the disulfide connectivity is basically the same
      for the differentially oxidized MU-SIIIA versions. 

PMID- 25376614
TI  - Impact of lesion location on the progression of osteoarthritis in a rat knee
      model.
AB  - To investigate how surgically created acute full-thickness cartilage defects of
      similar size and location created on the medial versus lateral femoral condyle
      influence progression of spontaneous cartilage lesions in a rat model. Full
      thickness cartilage defects of 1 mm were surgically created on the medial or
      lateral femoral condyles on the right leg of 20 rats (n = 10/group). Ten rats
      served as controls. Spontaneous lesion progression on the ipsilateral and
      contralateral surfaces was examined using a high-resolution digital camera along
      with H&E and Safranin-O staining. Chondral defects were scored grossly and
      histologically. Control femur displayed no cartilage disruption. Surgically
      treated knees exhibited created and spontaneous cartilage defects with no
      evidence of healing unless subchondral bone was penetrated. Ipsilateral
      spontaneous lesions on the lateral condyle were significantly more severe on
      average (p = 0.009) compared to medial lesions on gross examination. Histological
      examination found contralateral lesions on the lateral surface following
      surgically created medial lesions to be more severe (p = 0.057) compared to
      contralateral lesions. A trend toward more susceptible chondral damage to the
      lateral condyle was observed following acute lesion creation on either medial or
      lateral condyles. Mechanisms behind this pattern of spontaneous lesion
      development are unclear, requring further investigation.

PMID- 25376615
TI  - Electronic and Mechanical Coupling in Bent ZnO Nanowires.
AB  - A red shift of the exciton of ZnO nanowires is efficiently produced by bending
      strain, as demonstrated by a low-temperature (81 K) cathodoluminescence (CL)
      study of ZnO nanowires bent into L- or S-shapes. The figure shows a nanowire
      (Fig. a) with the positions of CL measurements marked. The corresponding CL
      spectra-revealing a peak shift and broadening in the region of the bend-are shown
      in Figure b. 

PMID- 25376616
TI  - The Effect of Vitamin D Supplementation on Thrombin Generation Assessed by the
      Calibrated Automated Thrombogram.
AB  - Observational and in vitro studies suggest that vitamin D may have antithrombotic
      activity. This study aimed to examine the relationship between vitamin D
      supplementation and thrombin generation. Serum 25-hydroxyvitamin D (25(OH)D) and
      thrombin generation parameters were measured in 73 healthy volunteers.
      Participants with serum 25(OH)D <50 nmol/L (n = 53) were treated with vitamin
      D3and tested for 25(OH)D and thrombin generation at the end of treatment. Lag
      time and time to peak decreased after treatment by a mean of -0.49 +/- 0.51
      minute (P< .001) and -0.76 +/- 0.70 minute (P< .001), respectively, whereas
      endogenous thrombin potential and peak height increased after treatment by a mean
      of 170.1 +/- 339.8 nmol/L minute (P= .001) and 34.2 +/- 47.8 nmol/L (P< .001),
      respectively. Treatment with vitamin D supplementation seems to have
      prothrombotic effect in patients with vitamin D insufficiency. These findings
      should be interpreted with caution and need to be replicated in future studies. 

PMID- 25376617
TI  - One year results of a phase 1 study of the safety and tolerability of combination
      therapy using sustained release intravitreal triamcinolone acetonide and
      ranibizumab for subfoveal neovascular AMD.
AB  - PURPOSE: To investigate safety and evidence of efficacy of IBI-20089, an
      intravitreal, liquid, sustained drug delivery system formulated with
      triamcinolone acetonide (TA) in combination with ranibizumab (Lucentis) for
      neovascular age related macular degeneration. METHODS: Patients received a single
      intravitreal injection of IBI-20089 containing either 6.9 mg (25 uL) TA or 13.8
      mg (50 uL) TA followed a week later by intravitreal injection of 0.5 mg
      ranibizumab. Patients were followed monthly and underwent best corrected visual
      acuity testing, slit lamp biomicroscopy, dilated ophthalmoscopy, fundus photos
      and optical coherence tomography. Patients received pro re nata dosing of
      ranibizumab. RESULTS: Patients ranged in age from 59 years to 81 years (mean 73.4
      years) and all completed 1 year follow-up. No serious related adverse events
      occurred. Ocular adverse events included mild, transient, elevated intraocular
      pressure in eight patients and cataract progression in three of the five phakic
      patients. At 1 year, 30 of a total 120 (25%) possible pro re nata re-Rx's had
      been given. Combination therapy resulted in a median number of 3.5 re-treatments
      at and including month 12. CONCLUSIONS: Combination therapy IBI-20089 and
      ranibizumab was well-tolerated and resulted in fewer ranibizumab retreatments.
      Transient intraocular pressure elevation and cataract progression occurred. TRIAL
      REGISTRATION NUMBER: NCT01175395.

PMID- 25376618
TI  - Phase II clinical trial of pasireotide long-acting repeatable in patients with
      metastatic neuroendocrine tumors.
AB  - Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA)
      with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3)
      and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can
      inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro.
      This open-label, phase II study assessed the clinical activity of pasireotide in
      treatment-naive patients with metastatic grade 1 or 2 NETs. Patients with
      metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR
      (60 mg every 4 weeks). Previous systemic therapy, including octreotide and
      lanreotide, was not permitted. Tumor assessments were performed every 3 months
      using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary
      endpoint was progression-free survival (PFS). The secondary endpoints included
      overall survival (OS), overall radiographic response rate (ORR), and safety.
      Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and
      28 were evaluable for response. The median PFS was 11 months. The most favorable
      effect was observed in patients with low hepatic tumor burden, normal baseline
      chromogranin A, and high tumoral SSTR5 expression. Median OS has not been
      reached; the 30-month OS rate was 70%. The best radiographic response was partial
      response in one patient (4%), stable disease in 17 patients (60%), and
      progressive disease in ten patients (36%). Although grade 3/4 toxicities were
      rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia
      including 14% grade 3 hyperglycemia. Although pasireotide appears to be an
      effective antiproliferative agent in the treatment of advanced NETs, the high
      incidence of hyperglycemia raises concerns regarding its suitability as a first
      line systemic agent in unselected patients. SSTR5 expression is a potentially
      predictive biomarker for response. 

PMID- 25376619
TI  - [Depression and anxiety disorders among psoriasis patients: protective and
      exacerbating factors].
AB  - BACKGROUND: Psoriasis is associated with higher risk for depression and anxiety
      disorders. Yet the complex system linking disease symptoms with physical and
      mental outcomes is poorly understood. OBJECTIVES: The central aim of this study
      was to identify physical, psychological, and social factors that exacerbate or
      protect against the perception of symptoms of depression and anxiety among
      individuals starting in-patient treatment for psoriasis. Another aim was to
      investigate if improved clinical status of the psoriasis is associated with
      improved psychological and physical wellbeing one year after treatment. MATERIALS
      AND METHODS: In this follow-up study a sample of 381 psoriasis in-patients in
      Germany were questioned before starting treatment and one year after treatment
      (166 participants) using instruments to measure socioeconomic variables,
      perceived somatic severity, life quality (DLQI, SF-8), feelings of stigmatization
      (QES), and depression and anxiety (HADS-D). Coping (Trier Coping Scale) and
      pathological worry (PSWQ-PW) were also measured at the initial time point.
      Multiple regression analyses of variance for repeated measurements and of
      correlation were conducted. RESULTS: Self-reported symptoms of anxiety and
      depression were higher than in normal populations. Perceived severity of physical
      symptoms was not correlated with depression or anxiety at the initial time point.
      The strongest predictors of depression and anxiety in our sample were measures of
      life quality. Life quality was predicted in a large part by stigmatization.
      Increased momentary symptom severity and increased perceived discomfort over time
      was not associated with increased perception of symptoms of depression.
      CONCLUSIONS: Our findings extend previous research on the importance of
      stigmatization for quality of life to the specific outcome of depression and
      anxiety. It confirms the desirability of early screening of psoriasis patients
      for depression and anxiety and initiating treatment by a qualified therapist.

PMID- 25376620
TI  - [Bullous pemphigoid: a new look at a well-known disease].
AB  - BACKGROUND: Bullous pemphigoid is an autoimmune blistering disease that is
      associated with appearance of subepidermal blisters. IgG antibodies against
      components of the epithelial basement membrane (BP 180 and 230 antigens) can be
      typically found in serum of patients. Direct immunofluorescence reveals usually a
      linear deposition of IgG and/or C3 along the basement membrane, but other
      immunoglobulins may also be present. CASE PRESENTATION: Our patient had no
      detectable formation of tense blisters of his skin; instead, the clinical picture
      was rather compatible with a prurigo simplex subacuta or a pruritic variant of
      atopic dermatitis. He also had a markedly elevated total serum IgE level. The
      diagnosis was confirmed by detection of circulating IgG against BP 180 in
      patient's serum in ELISA and detection of linear IgG deposits along the basement
      membrane zone of epidermis in the direct immunofluorescence. CONCLUSION: Atypical
      clinical presentations of bullous pemphigoid without blister formation are
      possible. Recent studies show that an increased total IgE level in serum of
      patients may occur frequently. The aim of this report is to provide the reader
      with a brief insight in the new findings in pathogenesis and therapy of bullous
      pemphigoid.

PMID- 25376621
TI  - [Double sensitization to PR10 and PR-14 proteins].
AB  - A patient with mild oral allergy syndrome presented with a history of anaphylaxis
      induced by both hazelnuts and peaches. The ensuing work-up showed a double
      sensitization to proteins in both pathogenesis-related group 10 (e.g. Bet v1, Cor
      a1, Pru p1) and 14 (e.g. Pru p3, Cor a8). Such double sensitization profiles are
      increasingly being recognized in Europe.

PMID- 25376623
TI  - Kentucky seeks $1bn from Purdue Pharma for misrepresenting addictive potential of
      oxycodone.

PMID- 25376622
TI  - Enhancing cell migration in shape-memory alginate-collagen composite scaffolds:
      In vitro and ex vivo assessment for intervertebral disc repair.
AB  - Lower lumbar disc disorders pose a significant problem in an aging society with
      substantial socioeconomic consequences. Both inner tissue (nucleus pulposus) and
      outer tissue (annulus fibrosus) of the intervertebral disc are affected by such
      debilitating disorders and can lead to disc herniation and lower back pain. In
      this study, we developed an alginate-collagen composite porous scaffold with
      shape-memory properties to fill defects occurring in annulus fibrosus tissue of
      degenerated intervertebral discs, which has the potential to be administered
      using minimal invasive surgery. In the first part of this work, we assessed how
      collagen incorporation on preformed alginate scaffolds influences the physical
      properties of the final composite scaffold. We also evaluated the ability of
      annulus fibrosus cells to attach, migrate, and proliferate on the composite
      alginate-collagen scaffolds compared to control scaffolds (alginate only). In
      vitro experiments, performed in intervertebral disc-like microenvironmental
      conditions (low glucose and low oxygen concentrations), revealed that for
      alginate only scaffolds, annulus fibrosus cells agglomerated in clusters with
      limited infiltration and migration capacity. In comparison, for alginate-collagen
      scaffolds, annulus fibrosus cells readily attached and colonized constructs,
      while preserving their typical fibroblastic-like cell morphology with spreading
      behavior and intense cytoskeleton expression. In a second part of this study, we
      investigated the effects of alginate-collagen scaffold when seeded with bone
      marrow derived mesenchymal stem cells. In vitro, we observed that alginate
      collagen porous scaffolds supported cell proliferation and extracellular matrix
      deposition (collagen type I), with secretion amplified by the local release of
      transforming growth factor-beta3. In addition, when cultured in ex vivo organ
      defect model, alginate-collagen scaffolds maintained viability of transplanted
      mesenchymal stem cells for up to 5 weeks. Taken together, these findings
      illustrate the advantages of incorporating collagen as a means to enhance cell
      migration and proliferation in porous scaffolds which could be used to augment
      tissue repair strategies. 

PMID- 25376624
TI  - Platelet-derived growth factor receptor-beta expression in human peritoneum.
AB  - INTRODUCTION: Simple peritoneal fibrosis and encapsulating peritoneal sclerosis
      (EPS) are important lesions in the peritoneum of patients on peritoneal dialysis
      (PD). We have previously described a population of podoplanin-positive
      myofibroblasts in peritoneal biopsies from patients with EPS. Platelet-derived
      growth factor receptor-beta (PDGFRbeta) is a marker of pericytes, and PDGFs might
      be involved in the fibrotic response of the peritoneum. This study aimed to
      describe PDGFRbeta in the human peritoneum. METHODS: In this retrospective
      analysis, we localized PDGFRbeta in peritoneal biopsies from patients with EPS (n
      = 6) and patients on PD without signs of EPS (n = 5), and compared them with
      normal peritoneum (n = 4) and peritoneum from uremic patients (n = 5).
      Consecutive sections were stained for smooth-muscle actin (SMA) and podoplanin.
      Slides were scored semiquantitatively by 2 observers blinded to the diagnosis.
      RESULTS: PDGFRbeta was expressed by cells of arterial walls in all biopsies. A
      prominent population of PDGFRbeta-positive cells was present in the normal
      peritoneum, which were SMA negative on consecutive sections. In patients on PD, a
      high number of PDGFRbeta were also positive for SMA. In EPS, the majority of
      podoplanin-positive cells were positive for PDGFRbeta. In peritoneal biopsies
      from normal and uremic patients, the expression of SMA was mainly restricted to
      cells of arterial walls. Podoplanin expression was restricted to lymphatic
      vessels in normal peritoneum, in uremic patients, and in patients on PD without
      EPS. CONCLUSIONS: As podoplanin-positive myofibroblasts express PDGFRbeta, these
      cells might be related to pericytes (rather than other sources of fibroblasts).
      PDGFRbeta might turn out to be a therapeutic target in EPS.

PMID- 25376625
TI  - Autogenous cultured growth plate chondrocyte transplantation in the treatment of
      physeal injury in rabbits.
AB  - OBJECTIVES: The aim of this experimental study on New Zealand's white rabbits was
      to investigate the transplantation of autogenous growth plate cells in order to
      treat the injured growth plate. They were assessed in terms of measurements of
      radiological tibial varus and histological characteristics. METHODS: An
      experimental model of plate growth medial partial resection of the tibia in 14
      New Zealand white rabbits was created. During this surgical procedure the plate
      growth cells were collected and cultured. While the second surgery was being
      performed, the autologous cultured growth plate cells were grafted at the right
      tibia, whereas the left tibia was used as a control group. RESULTS: Histological
      examinations showed that the grafted right tibia presented the regular shape of
      the plate growth with hypertrophic maturation, chondrocyte columniation and
      endochondral calcification. Radiological study shows that the mean tibial
      deformity at the left angle was 20.29 degrees  (6.25 to 33) and 7.21 degrees  (5
      to 10) in the right angle. CONCLUSION: This study has demonstrated that grafting
      of autogenous cultured growth plate cells into a defect of the medial aspect of
      the proximal tibial physis can prevent bone bridge formation, growth arrest and
      the development of varus deformity. Cite this article: Bone Joint Res 2014;3:310
      16.

PMID- 25376626
TI  - A direct action for GH in improvement of oocyte quality in poor-responder
      patients.
AB  - Declining female fecundity at later age and the increasing tendency for women to
      delay childbirth have lead to a drastic rise in the number of women seeking
      assisted reproductive technology. Many women fail to respond adequately to
      standard ovarian stimulation regimens, raising a significant therapeutic
      challenge. Recently, we have demonstrated that the administration of GH, as an
      adjunct to ovarian stimulation, has improved the clinical outcomes by enhancing
      the oocyte quality. However, the mechanism(s) by which GH facilitated this
      improvement is yet to be understood. This study aimed to determine these
      potential mechanism(s) through the use of immunofluorescent localisation of GH
      receptors (GHRs) on the human oocyte and unbiased computer-based quantification
      to assess and compare oocyte quality between women of varying ages, with or
      without GH treatment. This study demonstrates for the first time, the presence of
      GHRs on the human oocyte. The oocytes retrieved from older women showed
      significant decrease in the expression of GHRs and amount of functional
      mitochondria when compared with those from younger patients. More interestingly,
      when older patients were treated with GH, a significant increase in functional
      mitochondria was observed in their oocytes. We conclude that GH exerts a direct
      mode of action, enabling the improvement of oocyte quality observed in our
      previous study, via the upregulation of its own receptors and enhancement of
      mitochondrial activity. This result, together with recent observations, provides
      scientific evidence in support of the use of GH supplementation for the clinical
      management of poor ovarian response. 

PMID- 25376627
TI  - Alteration in the intrafollicular thiol-redox system in infertile women with
      endometriosis.
AB  - The aim of this study was to compare intrafollicular biomarkers of thiol-redox
      system and chronic inflammation in infertile patients with and without
      endometriosis, and examine correlations between biomarkers and IVF outcomes. The
      study included 65 patients receiving IVF: 31 patients with endometriosis vs 34
      patients without endometriosis. Follicular fluid (FF) was obtained from a single
      dominant follicle during oocyte retrieval and stored at -70  degrees C.
      Malondialdehyde, superoxide dismutase, glutathione (GSH), glutathione peroxidase
      3 (GPX3), thioredoxin (TRX), TRX-binding protein 2 (TBP2), and peroxiredoxin-4
      levels were measured in the FF samples by ELISAs as biomarkers of oxidative
      stress. The inflammatory cytokines interleukin 1 beta (IL1beta), IL6, IL8, and
      tumor-necrosis factor alpha (TNFalpha) were also measured by ELISAs. GSH levels
      were significantly lower in the endometriosis group compared with the controls.
      TBP2 levels were significantly higher in the endometriosis group. IL6, IL8, and
      TNFalpha levels were significantly higher in the endometriosis group. The levels
      of all of the inflammatory cytokines positively correlated with the levels of
      TRX. GSH levels positively correlated with the number of high-quality embryos.
      GPX3 and TRX levels negatively correlated with the percentage of mature oocytes.
      TNFalpha levels negatively correlated with the cumulative embryo score per
      embryo. Logistic regression analysis revealed that the number of high-quality
      embryos was an independent factor predicting clinical pregnancy. In conclusion,
      there may be an imbalance in the thiol-redox system and increased levels of
      inflammatory cytokines in the intrafollicular microenvironment of infertile
      patients with endometriosis, which may affect the qualities of the oocyte and
      embryo. 

PMID- 25376629
TI  - Obama vows to defend key elements of Affordable Care Act.

PMID- 25376628
TI  - Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast
      formation and induce regulatory B cells independently of T helper cells.
AB  - Mesenchymal or stromal stem cells (MSC) interact with cells of the immune system
      in multiple ways. Modulation of the immune system by MSC is believed to be a
      therapeutic option for autoimmune disease and transplant rejection. In recent
      years, B cells have moved into the focus of the attention as targets for the
      treatment of immune disorders. Current B-cell targeting treatment is based on the
      indiscriminate depletion of B cells. The aim of this study was to examine whether
      human adipose tissue-derived MSC (ASC) interact with B cells to affect their
      proliferation, differentiation, and immune function. ASC supported the survival
      of quiescent B cells predominantly via contact-dependent mechanisms. Coculture of
      B cells with activated T helper cells led to proliferation and differentiation of
      B cells into CD19(+) CD27(high) CD38(high) antibody-producing plasmablasts. ASC
      inhibited the proliferation of B cells and this effect was dependent on the
      presence of T cells. In contrast, ASC directly targeted B-cell differentiation,
      independently of T cells. In the presence of ASC, plasmablast formation was
      reduced and IL-10-producing CD19(+) CD24(high) CD38(high) B cells, known as
      regulatory B cells, were induced. These results demonstrate that ASC affect B
      cell biology in vitro, suggesting that they can be a tool for the modulation of
      the B-cell response in immune disease.

PMID- 25376630
TI  - Sinonasal and ventral skull base inflammatory pseudotumor: a systematic review.
AB  - OBJECTIVES/HYPOTHESIS: Inflammatory pseudotumor is a benign idiopathic
      inflammatory process often misdiagnosed as an infection or neoplasm. This review
      analyzes all reported cases of sinonasal and ventral skull base inflammatory
      pseudotumor to date, and provides a framework for evaluation and management of
      this uncommon condition. DATA SOURCES: MEDLINE/PubMed database. REVIEW METHODS: A
      search for articles related to sinonasal and ventral skull base inflammatory
      pseudotumor, along with bibliographies of those articles, was performed.
      Demographics, presentation, radiographic findings, treatment, follow-up, and
      outcome were analyzed. RESULTS: Thirty-three articles were reviewed, including a
      total of 87 patients. The most common presenting symptom was vision change
      (58.6%). Sinonasal and ventral skull base inflammatory pseudotumor was found in
      the cavernous sinus in 46.0% of cases. The lesion appeared isointense (66.7% of
      cases) and homogeneously enhancing on T1-weighted magnetic resonance imaging
      (MRI), whereas it appeared hypointense on T2-weighted MRI in 90.7% of cases.
      Inflammatory pseudotumor appeared hyperdense on computed tomography in 78.9% of
      cases. Histopathological analysis of biopsied specimens revealed presence of
      inflammatory cells (94.4%) and fibrosis (80.3%). Corticosteroids alone were the
      most common treatment modality (55.2%), resulting in disease-free patients in
      22.9% of cases over a median follow-up period of 17.6 months. Surgical management
      alone was uncommon (8.0%), but showed high success rate (57.1%). CONCLUSION: This
      review is the most comprehensive analysis of sinonasal and ventral skull base
      inflammatory pseudotumor to date. Radiologic findings and histopathological
      analysis are essential for diagnosis. Corticosteroids are the most common
      treatment modality. Surgery, although uncommon, appears to be an efficacious
      treatment modality.

PMID- 25376632
TI  - A new approach used to explore associations of current Ambrosia pollen levels
      with current and past meteorological elements.
AB  - The paper examines the sensitivity of daily airborne Ambrosia (ragweed) pollen
      levels of a current pollen season not only on daily values of meteorological
      variables during this season but also on the past meteorological conditions. The
      results obtained from a 19-year data set including daily ragweed pollen counts
      and ten daily meteorological variables are evaluated with special focus on the
      interactions between the phyto-physiological processes and the meteorological
      elements. Instead of a Pearson correlation measuring the strength of the linear
      relationship between two random variables, a generalised correlation that
      measures every kind of relationship between random vectors was used. These latter
      correlations between arrays of daily values of the ten meteorological elements
      and the array of daily ragweed pollen concentrations during the current pollen
      season were calculated. For the current pollen season, the six most important
      variables are two temperature variables (mean and minimum temperatures), two
      humidity variables (dew point depression and rainfall) and two variables
      characterising the mixing of the air (wind speed and the height of the planetary
      boundary layer). The six most important meteorological variables before the
      current pollen season contain four temperature variables (mean, maximum, minimum
      temperatures and soil temperature) and two variables that characterise large
      scale weather patterns (sea level pressure and the height of the planetary
      boundary layer). Key periods of the past meteorological variables before the
      current pollen season have been identified. The importance of this kind of
      analysis is that a knowledge of the past meteorological conditions may contribute
      to a better prediction of the upcoming pollen season. 

PMID- 25376631
TI  - Single and combined effects of zinc and cinnamon essential oil in diet on
      productive performance, egg quality traits, and blood parameters of laying hens
      reared under cold stress condition.
AB  - This study was conducted to evaluate the effects of adding zinc (Zn), cinnamon
      essential oil (Ci), or their combination in diet on productive performance, egg
      quality, and blood parameters of laying hens reared under cold stress condition
      (8.8 +/- 3  degrees C). Feed intake (FI), feed conversion ratio (FCR), egg weight
      (EW), egg production (EP), and egg mass (EM) were evaluated during the 56-day
      trial period using 120 Lohmann LSL-Lite laying hens. Significant interactions
      between Ci and Zn on FCR, EW, EP, or EM were observed (P < 0.05). The EP, EM, and
      EW increased, whereas FCR decreased (P < 0.05) in the hens fed the diets
      including Ci and Zn (as single or combined form) compared to those fed the basal
      diet. There were significant interactions between Ci and Zn on the serum level of
      glucose and triglycerides as well as plasma concentration of zinc (P < 0.05), so
      that serum content of glucose and triglyceride decreased and the plasma content
      of zinc increased in the hens fed the diets including Ci and Zn (together)
      compared to those fed the basal diet. From the results of the present experiment,
      it can be concluded that diet supplementation by the combined form of Ci and Zn
      could have beneficial effects on performance and blood parameters of hens reared
      under cold stress condition.

PMID- 25376633
TI  - Gold-nanoparticle-based multifunctional amyloid-beta inhibitor against
      Alzheimer's disease.
AB  - Targeting amyloid-beta (Abeta)-induced complex neurotoxicity has received
      considerable attention in the therapeutic and preventive treatment of Alzheimer's
      disease (AD). The complex pathogenesis of AD suggests that it requires
      comprehensive treatment, and drugs with multiple functions against AD are more
      desirable. Herein, AuNPs@POMD-pep (AuNPs: gold nanoparticles, POMD:
      polyoxometalate with Wells-Dawson structure, pep: peptide) were designed as a
      novel multifunctional Abeta inhibitor. AuNPs@POMD-pep shows synergistic effects
      in inhibiting Abeta aggregation, dissociating Abeta fibrils and decreasing Abeta
      mediated peroxidase activity and Abeta-induced cytotoxicity. By taking advantage
      of AuNPs as vehicles that can cross the blood-brain barrier (BBB), AuNPs@POMD-pep
      can cross the BBB and thus overcome the drawbacks of small-molecule anti-AD
      drugs. Thus, this work provides new insights into the design and synthesis of
      inorganic nanoparticles as multifunctional therapeutic agents for treatment of
      AD. 

PMID- 25376634
TI  - Histopathologic and immunohistological evaluation of anaplastic large cell
      lymphoma with Epstein-Barr virus in an orangutan (Pongo pygmaeus).
AB  - BACKGROUND: An 18-month-old female orangutan (Pongo pygmaeus) died after
      exhibiting fever, cough, and rapid breathing. METHODS AND RESULTS: Based on
      serological, virological, histopathological and immunohistochemical examination,
      anaplastic large cell lymphoma was confirmed. CONCLUSION: To the best of our
      knowledge, this is the first report of anaplastic large cell lymphoma associated
      with Epstein-Barr virus (EBV) in an orangutan.

PMID- 25376635
TI  - Evaluation of the marsh deer stifle joint by imaging studies and gross anatomy.
AB  - This study aimed to evaluate the stifle joint of marsh deer using imaging studies
      and in comparison with gross anatomy. Ten hindlimbs from 5 marsh deer
      (Blastocerus dichotomus) were used. Radiography, computed tomography (CT) and
      magnetic resonance imaging (MRI) were performed in each stifle joint. Two
      hindlimbs were dissected to describe stifle gross anatomy. The other limbs were
      sectioned in sagittal, dorsal or transverse planes. In the craniocaudal
      radiographic view, the lateral femoral condyle was broader than the medial
      femoral condyle. The femoral trochlea was asymmetrical. Subsequent multiplanar
      reconstruction revealed in the cranial view that the external surface of the
      patella was roughened, the medial trochlea ridge was larger than the lateral one,
      and the extensor fossa at the lateral condyle was next to the lateral ridge. The
      popliteal fossa was better visualized via the lateral view. Sagittal MRI images
      identified lateral and medial menisci, caudolateral and craniomedial bundles of
      cranial cruciate ligament, caudal cruciate ligament, patellar ligament and common
      extensor tendon. In conclusion, the marsh deer stifle presents some anatomical
      characteristics of the ovine stifle joint. 

PMID- 25376636
TI  - Reply to the letter by Wu et al. entitled 'Care and prudence as main directive in
      clinical research on neurosurgical intervention for schizophrenia'.

PMID- 25376638
TI  - Ebola virus disease: understanding the facts, putting fears in perspective, and
      being prepared.

PMID- 25376637
TI  - Effect of reporting bias in the analysis of spontaneous reporting data.
AB  - It is well-known that a spontaneous reporting system suffers from significant
      under-reporting of adverse drug reactions from the source population. The
      existing methods do not adjust for such under-reporting for the calculation of
      measures of association between a drug and the adverse drug reaction under study.
      Often there is direct and/or indirect information on the reporting probabilities.
      This work incorporates the reporting probabilities into existing methodologies,
      specifically to Bayesian confidence propagation neural network and DuMouchel's
      empirical Bayesian methods, and shows how the two methods lead to biased results
      in the presence of under-reporting. Considering all the cases to be reported, the
      association measure for the source population can be estimated by using only
      exposure information through a reference sample from the source population.

PMID- 25376639
TI  - Racial differences in abnormal ambulatory blood pressure monitoring measures:
      Results from the Coronary Artery Risk Development in Young Adults (CARDIA) study.
AB  - BACKGROUND: Several ambulatory blood pressure monitoring (ABPM) measures have
      been associated with increased cardiovascular disease risk independent of clinic
      blood pressure (BP). African Americans have higher clinic BP compared with Whites
      but few data are available on racial differences in ABPM measures. METHODS: We
      compared ABPM measures between African American (n = 178) and White (n = 103)
      participants at the Year 5 Coronary Artery Risk Development in Young Adults study
      visit. BP was measured during a study visit and the second and third measurements
      were averaged. ABPM was conducted over the following 24 hours. RESULTS: Mean +/-
      SD age of participants was 29.8 +/- 3.8 years and 30.8 +/- 3.5 years for African
      Americans and Whites, respectively. Mean daytime systolic BP (SBP) was 3.90 (SD
      1.18) mm Hg higher among African Americans compared with Whites (P < 0.001) after
      age-gender adjustment and 1.71 (SD 1.03) mm Hg higher after multivariable
      adjustment including mean clinic SBP (P = 0.10). After multivariable adjustment
      including mean clinic SBP, nighttime SBP was 4.83 (SD 1.11) mm Hg higher among
      African Americans compared with Whites (P < 0.001). After multivariable
      adjustment, the African Americans were more likely than Whites to have nocturnal
      hypertension (prevalence ratio: 2.44, 95% CI: 0.99-6.05) and nondipping
      (prevalence ratio: 2.50, 95% CI: 1.39-4.48). The prevalence of masked
      hypertension among African Americans and Whites was 4.4% and 2.1%, respectively,
      (P = 0.49) and white coat hypertension was 3.3% and 3.9%, respectively (P =
      0.99). Twenty-four hour BP variability on ABPM was higher among African Americans
      compared with Whites. CONCLUSIONS: These data suggest racial differences in
      several ABPM measures exist.

PMID- 25376640
TI  - Intrafamilial aggregation and heritability of left ventricular geometric
      remodeling is independent of cardiac mass in families of African ancestry.
AB  - BACKGROUND: Whether left ventricular (LV) geometric remodeling, as indexed by
      relative wall thickness (RWT), aggregates in families and is inherited
      independent of LV mass (LVM) and additional confounders is uncertain. METHODS: We
      determined whether RWT as assessed from 2D targeted M-mode echocardiography shows
      intrafamilial aggregation and heritability independent of LVM in 181 nuclear
      families (73 spouse pairs, 403 parent-child pairs, and 177 sibling-sibling pairs)
      with 16 families including 3 generations from an urban developing community of
      black Africans. Intrafamilial aggregation and heritability estimates (S.A.G.E.
      software) were assessed independent of confounders, including central aortic
      systolic blood pressure (SBPc) (radial applanation tonometry and SphygmoCor
      software). RESULTS: Independent of confounders including SBPc, LV RWT was
      correlated in parent-child (r = 0.32, P < 0.0001) and sibling-sibling (r = 0.29,
      P < 0.0001), but not in spouse (r = 0.11, P = 0.33) pairs. The relationships
      between parent-child (r = 0.28, P < 0.0001) and sibling-sibling (r = 0.24, P <
      0.001) pairs persisted with further adjustments for LVM or LVM indexed to
      height(2.7) (LVMI). Similarly, independent of confounders, LV RWT showed
      significant heritability (h(2) +/- SEM = 0.56 +/- 0.09, P < 0.0001) and this
      persisted with further adjustments for LVM (h(2) +/- SEM = 0.48 +/- 0.09, P <
      0.0001) or LVMI (h(2) +/- SEM = 0.49 +/- 0.09, P < 0.0001). CONCLUSIONS: In a
      group of African ancestry, independent of LVM, LV geometric remodeling shows
      significant intrafamilial aggregation and heritability. Genetic factors may in
      part determine the LV geometric remodeling process independent of the extent of
      cardiac hypertrophy.

PMID- 25376641
TI  - Blood pressure in healthy pregnancy and factors associated with no mid-trimester
      blood pressure drop: a prospective cohort study.
AB  - BACKGROUND: The well-known mid-trimester drop in blood pressure (BP) during
      normal pregnancy was recently questioned. OBJECTIVE: To describe longitudinal
      changes in BP during healthy pregnancies and to investigate factors associated
      with no mid-trimester drop in BP. METHODS: A prospective cohort with 158 healthy
      pregnant women was followed up in a public health care center in Rio de Janeiro,
      Brazil. We used linear mixed-effects models to estimate longitudinal changes in
      systolic BP (SBP) and diastolic BP (DBP) during pregnancy. Poisson regression
      models were performed to identify factors associated with no mid-trimester drop
      in BP. RESULTS: Significant mid-trimester increase in SBP (5.6 mm Hg; 95%
      confidence interval (CI) = 4.6-6.7) and DBP (4.4 mm Hg; 95% CI = 3.4-5.3) was
      observed in 44.3% and 39.9% of the sample, respectively. Women (37.1%) who had
      not a mid-trimester SBP drop still had a DBP drop. White skin color (incidence
      ratio (IR): 1.71; 95% CI = 1.22-2.39), family history of hypertension (IR: 1.93;
      95% CI = 1.29-2.89), early pregnancy obesity (IR: 2.29; 95% CI = 1.27-4.11),
      outside temperature variation (IR: 1.45; 95% CI = 1.00-2.10), and gestational
      weight gain from the first to second trimester (IR: 1.71; 95% CI = 1.01-2.88 and
      IR: 2.32; 95% CI = 1.39-3.89 for second and third tertiles) were characteristics
      associated with no mid-trimester drop in SBP. The same characteristics were
      associated with no mid-trimester drop in DBP, except family history of
      hypertension and outside temperature variation. CONCLUSIONS: Some women without a
      mid-trimester SBP drop still present a DBP drop. The different patterns of mid
      trimester change in BP seem to be determined by preexisting and pregnancy-related
      factors.

PMID- 25376642
TI  - Trophoblast syncytialisation necessitates mitochondrial function through estrogen
      related receptor-gamma activation.
AB  - Human pregnancy needs a correct placentation which depends on adequate
      cytotrophoblast proliferation, differentiation and invasion. In this study, using
      specific mitochondrial respiratory chain inhibitors, we observed a decrease of
      hormone production (hCG and leptin) and cell fusion of human primary villous
      cytotrophoblasts (CT). These results demonstrated that mitochondria are involved
      in the control of CT differentiation process. Moreover, we also observed a
      decrease of mitochondrial mass associated with an increase of mitochondrial DNA
      during CT differentiation. Furthermore, lactate production increased during CT
      differentiation suggesting that anaerobic metabolism was enhanced in
      differentiated CTs, and that the role of mitochondria in CT fusion is not only
      related to its energetic function. Otherwise, the orphan nuclear receptor,
      estrogen-related receptor gamma (ERRgamma) is known to orchestrate
      transcriptional control of energy metabolism genes. In this study, using RNA
      knockdown and transcriptional activation with DY131 (an ERRgamma agonist), we
      clearly demonstrated that ERRgamma promotes hormone production and cell fusion
      indicating that ERRgamma is a key positive transcriptional factor involved in CT
      differentiation. Finally, we showed that ERRgamma promotes mitochondrial
      biogenesis and function during CT differentiation, and that the role of ERRgamma
      during trophoblast differentiation is mainly mediated by the control of
      mitochondrial functions. 

PMID- 25376643
TI  - Is non-invasive ventilation safe in acute severe asthma?
AB  - BACKGROUND AND OBJECTIVE: The effect of non-invasive ventilation (NIV) in acute
      severe asthma is unclear and there are concerns regarding its safety. METHODS: We
      undertook a 5-year case-control review of mortality and morbidity associated with
      NIV use in acute severe asthma and compared this with asthma requiring invasive
      mechanical ventilation (IMV) and a control group with less severe asthma without
      ventilatory support. RESULTS: Eight hundred seventy-three patients had acute
      severe asthma of whom 30 were treated with NIV, 17 with IMV and 90 served as
      controls. The mean duration of NIV was 9.5 +/- 7.3 h with inspiratory positive
      airway pressure and expiratory positive airway pressure of 11.9 +/- 1.4 and 5.8
      +/- 1.2 cmH2 O respectively. Mortality was zero in the NIV and control groups,
      compared with 41% in the IMV group. None of the NIV or control groups required
      escalation to invasive ventilation. There were no instances of haemodynamic
      compromise in the NIV or control groups. Length of hospital stay was 121 +/- 96 h
      in the NIV group and similar to the severe IMV group (136 +/- 99 h, P > 0.05) and
      significantly longer than the control group (42 +/- 40 h, P < 0.05). CONCLUSIONS:
      NIV can be safely used in acute severe asthma although further work is needed to
      delineate the precise patient selection process.

PMID- 25376644
TI  - Clues to the signals for chloroplast photo-relocation from the lifetimes of
      accumulation and avoidance responses.
AB  - Chloroplast photo-relocation movement is crucial for plant survival; however, the
      mechanism of this phenomenon is still poorly understood. Especially, the signal
      that goes from photoreceptor to chloroplast is unknown, although the
      photoreceptors (phototropin 1 and 2) have been identified and an actin structure
      (chloroplast actin filaments) has been characterized that is specific for
      chloroplast movement. Here, in gametophytes of the fern Adiantum capillus
      veneris, gametophores of the moss Physcomiterella patens, and leaves of the seed
      plant Arabidopsis thaliana, we sought to characterize the signaling system by
      measuring the lifetime of the induced response. Chloroplast movements were
      induced by microbeam irradiation with high-intensity blue light and recorded. The
      lifetime of the avoidance state was measured as a lag time between switching off
      the beam and the loss of avoidance behavior, and that of the accumulation state
      was measured as the duration of accumulation behavior following the extinction of
      the beam. The lifetime for the avoidance response state is approximately 3-4 min
      and that for the accumulation response is 19-28 min. These data suggest that the
      two responses are based on distinct signals.

PMID- 25376645
TI  - Atomic imaging of phase transitions and morphology transformations in
      nanocrystals.
AB  - A newly developed SiN microhotplate allows specimens to be studied at
      temperatures up to 1000 K at a resolution of 100 picometer. Aberration-corrected
      transmission electron microscopy has become a commonplace tool to investigate
      stable crystals; however, imaging transient nanocrystals is much more demanding.
      Morphological transformations in gold nanoparticles and layer-by-layer
      sublimation of PbSe nanocrystals is imaged with atomic resolution. 

PMID- 25376647
TI  - Inherited predisposition to endometrial cancer: moving beyond Lynch syndrome.

PMID- 25376646
TI  - NAA10 controls osteoblast differentiation and bone formation as a feedback
      regulator of Runx2.
AB  - Runt-related transcription factor 2 (Runx2) transactivates many genes required
      for osteoblast differentiation. The role of N-alpha-acetyltransferase 10 (NAA10,
      arrest-defective-1), originally identified in yeast, remains poorly understood in
      mammals. Here we report a new NAA10 function in Runx2-mediated osteogenesis.
      Runx2 stabilizes NAA10 in osteoblasts during BMP-2-induced differentiation, and
      NAA10 in turn controls this differentiation by inhibiting Runx2. NAA10 delays
      bone healing in a rat calvarial defect model and bone development in neonatal
      mice. Mechanistically, NAA10 acetylates Runx2 at Lys225, and this acetylation
      inhibits Runx2-driven transcription by interfering with CBFbeta binding to Runx2.
      Our study suggests that NAA10 acts as a guard ensuring balanced osteogenesis by
      fine-tuning Runx2 signalling in a feedback manner. NAA10 inhibition could be
      considered a potential strategy for facilitating bone formation. 

PMID- 25376648
TI  - Patients' experiences of being mechanically ventilated in an ICU: a qualitative
      metasynthesis.
AB  - BACKGROUND: Being a patient in an intensive care unit (ICU) and being
      mechanically ventilated is a scary and unpleasant experience to many patients.
      Qualitative studies describe these Patients' experiences, but the findings have
      not yet been synthesised. AIM: The aim of this study was to gather and synthesise
      interpreted knowledge from qualitative studies about Patients' experiences of
      being mechanically ventilated in an ICU. METHOD: A qualitative metasynthesis was
      conducted on findings from nine qualitative studies performed in the period from
      1994 to 2012. The studies were critically appraised according to the method
      defined by Sandelowski and Barosso, and the findings were extracted, edited,
      grouped and abstracted. Subsequently, the abstracted findings were analysed,
      using the constant comparison analysis. In the analysis, we used findings from
      patients with home ventilation and findings from patients admitted to an ICU,
      while they were not ventilated. RESULTS: Fifteen abstracted findings appeared
      from the metasynthesis and led to the synthesised finding: 'Being dependent on
      health professionals, without being able to communicate, causes experiences with
      anxiety, fear and loneliness. How intensively these feelings are experienced
      seems to depend on the health professionals' ability of being present with these
      patients. The presence of relatives can alleviate these experiences'. CONCLUSION:
      This study shows that patients being mechanically ventilated in an ICU experience
      an emic vulnerability, consisting of anxiety, fear and loneliness. IMPLICATIONS
      FOR PRACTICE: In future practice, it is expected that patients will be more awake
      during mechanical ventilation. It is therefore important that health
      professionals have the knowledge that their presence and their support of the
      relationship between the patient and his/her relatives are of great importance in
      the care of patients.

PMID- 25376649
TI  - Assisted reproductive technologies (ARTs): evaluation of evidence to support
      public policy development.
AB  - Over the years, IVF/ICSI protocols have continued to evolve with efforts to
      improve outcomes. As a result, treatment success may be related to certain
      procedural factors, including number of embryos transferred and stage at which
      they are transferred. This review aims to assess the safety and effectiveness of
      IVF/ICSI in comparison to spontaneous conception and less invasive ARTs and the
      impact of procedure-related factors on the outcomes of IVF/ICSI in order to
      support the development of local clinical and policy guidance. Following Cochrane
      Collaboration guidelines and the PRISMA statement, a comprehensive systematic
      review of literature examining the impact of procedural characteristics on the
      safety or effectiveness of IVF/ICSI from 2007 to date was performed. 33
      systematic reviews and 3 primary studies evaluating the impact of procedural
      differences, IVF/ICSI in comparison to less invasive ARTs, and ARTs in comparison
      to spontaneous conception were found. IVF was shown to offer significant benefits
      over no treatment and IUI in achieving pregnancy and live birth among couples
      with endometriosis or unexplained infertility. Frozen and blastocyst-stage embryo
      transfers were as effective as fresh and cleavage-stage embryo transfers,
      respectively. In comparison to single embryo transfer, double embryo transfer
      significantly increased pregnancy, live birth and multiple pregnancy/birth rates.
      IVF/ICSI was associated with more complications during pregnancy and delivery,
      and in infants compared to naturally conceived pregnancies, particularly when
      multiple embryo transfer was used. Frozen embryo transfer had fewer adverse
      events during pregnancy and delivery than fresh embryo transfer, and was at least
      as safe in terms of infant outcomes. The potential complications of IVF/ICSI may
      be minimized through procedural choices, but such choices often impact
      effectiveness. Thus, in developing clinical and policy guidance around IVF/ICSI,
      the risk-benefit trade-offs patients and providers are willing to accept must be
      carefully considered. 

PMID- 25376650
TI  - Real-time observation and control of pentacene film growth on an artificially
      structured substrate.
AB  - Suppression of nucleation around a gold electrode during pentacene growth on a
      SiO2 channel is found by photoemission electron microscopy. Mass flow is driven
      by the difference between the molecular orientations on SiO2 and gold. The poor
      connectivity at the channel/electrode boundary causes degradation in the
      performance of a field-effect transistor, which is found to be improved by self
      assembled monolayer treatment on the electrode (see figure; thickness in
      monolayers (ML)). 

PMID- 25376651
TI  - Natural control of corn postharvest fungi Aspergillus flavus and Penicillium sp.
      using essential oils from plants grown in Argentina.
AB  - The objective in this study was to evaluate the antifungal activity of essential
      oils from native and commercial aromatic plants grown in Argentina against corn
      postharvest fungi and to link the essential oil bioactivity with lipid oxidation
      and morphological changes in fungus cell membrane. Essential oil (EO) of oregano
      variety Mendocino (OMen), Cordobes (OCor), and Compacto (OCom), mint variety
      Inglesa (Mi), and Pehaujo (Mp), Suico (Sui); rosemary (Ro), and Aguaribay (Ag)
      were tested in vitro against 4 corn fungi: A. flavus (CCC116-83 and BXC01), P.
      oxalicum (083296), and P. minioluteum (BXC03). The minimum fungicidal
      concentration (MFC) and the minimum inhibitory concentration (MIC) were
      determined. The chemical profiles of the EOs were analyzed by GC-MS. Lipid
      oxidation in cell membrane of fungi was determined by hydroperoxides and related
      with essential oil antifungal activity. The major compounds were Thymol in OCor
      (18.66%), Omen (12.18%), and OCom (9.44%); menthol in Mi and Mp; verbenone in
      Sui; dehydroxy-isocalamendiol in Ag; and eucaliptol in Ro. OCor, Omen, and OCom
      showed the best antifungal activity. No antifungal activity was observed in Ag
      and Ro EO. The hydroperoxide value depended on the fungi (P < 0.001) and the
      antimicrobial agent (P < 0.001).Membrane lipids were oxidized by Sui EO in A.
      flavus BXC01 and A. flavus CCC116-83 (0.021 and 0.027 meqO2 /kg, respectively).
      The results suggest that the EOs of OCor, OMen, OCom, Mi, Mp, and Sui grown in
      Argentina can be used as natural alternatives to control fungi that produce
      mycotoxin in maize. 

PMID- 25376652
TI  - Conformational transformations of sulfur-containing rings: 2
      methyltetrahydrothiophene gas-phase structures.
AB  - Stable conformations of five-member rings with the prototype cyclopentane are
      well-known to exist as twist or envelope structures and are of general interest
      in chemistry. Here, we report on the conformational analysis of the sulfur
      containing ring 2-methyltetrahydrothiophene studied by a combination of molecular
      beam Fourier transform microwave (MB-FTMW) spectroscopy and quantum chemistry.
      Two twist conformers were observed, whereby highly accurate molecular parameters
      could be determined. In addition, the (34) S-isotopologue of the most stable
      conformer was assigned in natural abundances. Geometry optimizations were
      performed at different levels of theory and the calculated rotational constants
      were compared with experimental values. Two transition states optimized at the
      MP2/6-311++G(d,p) level using the Berny algorithm could illustrate the
      intramolecular conversion between both conformers. 

PMID- 25376653
TI  - Health-related quality of life in children with flexible flatfeet: a cross
      sectional study.
AB  - PURPOSE: The effect of paediatric flexible flatfeet (PFF) on health-related
      quality of life (HRQOL) has not been investigated. In this prospective cross
      sectional study, the HRQOL of children with PFF was compared to those with
      typically developing feet (TDF) using two validated measures. We hypothesised
      that reduced HRQOL would be observed in children with PFF. The reliability of
      parents' perceptions of their child's symptoms was also investigated. METHODS: 48
      children with PFF and 47 with TDF between the ages of 8 and 15 completed The
      Oxford Ankle Foot Questionnaire for Children (OxAFQ-C) and Pediatric Quality of
      Life Inventory (PedsQLTM 4.0). Proxy questionnaires were also completed.
      Reliability of parent and child questionnaire scores was assessed using the
      intraclass correlation coefficient (ICC) and Student's t test. Differences
      between HRQOL between PFF and TDF were assessed using the Student's t test.
      RESULTS: ICCs overall demonstrated good reliability between parent and child
      questionnaire domain scores. There was a tendency for parents to overestimate the
      impairment of the child in the PFF group. PFF children demonstrated clinically
      significant decreased HRQOL than TDF children. This was most marked in the
      physical domain scores. CONCLUSION: Although parents may overestimate their
      child's impairment, children with PFF still have significantly impaired HRQOL
      when compared to TDF children. The impairment can be as severe, or worse, than
      published HRQOL for acutely and chronically unwell children. As such, PFF cannot
      be regarded as just a benign normal variant. The management of PFF should involve
      consideration of the symptom profile and HRQOL. LEVEL OF EVIDENCE: II.

PMID- 25376654
TI  - Characterization of the clonal profile of MRSA isolated in neonatal and pediatric
      intensive care units of a University Hospital.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) are important
      pathogens in neonatal and pediatric intensive care units, which can cause severe
      infections in hospitalized children. Detection of the mecA gene and
      classification of the staphylococcal cassette chromosome mec (SCCmec) permit the
      characterization of MRSA strains isolated from infections caused by these
      microorganisms. In contrast, pulsed-field gel electrophoresis (PFGE) is used to
      type MRSA clones. This method is commonly used to analyze the epidemiology of
      bacteria causing nosocomial infections. The objective of this study was to detect
      and characterize MRSA isolated from clinical specimens of children hospitalized
      in the neonatal and pediatric intensive care units of the University Hospital of
      the Botucatu Medical School. METHODS: A total of 119 S. aureus strains were
      isolated from clinical specimens and the mecA gene was detected by PCR. SCCmec
      was detected by multiplex PCR and the clonal profile was analyzed by PFGE.
      RESULTS: The mecA gene was detected in 17.6% (21/119) of the isolates; 42.9%
      (9/21) of MRSA were characterized as SCCmec type III and 57.1% (12/21) as type
      IV. Analysis of the clonal profile of these strains revealed three distinct
      clones, with SCCmec type III being related to the Brazilian endemic clone and
      type IV to clones JCSC4469 and USA800. CONCLUSIONS: Replacement of clonal groups
      occurred in the neonatal and pediatric units over the period studied, a fact
      highlighting the importance of improving hygiene practices and control measures
      of nosocomial infections in these units.

PMID- 25376655
TI  - The clinical course of cirrhosis: The importance of multistate models and
      competing risks analysis.
AB  - Multistate models are models of disease progression that, for a patient group,
      define multiple outcome events, each of which may affect the time to develop
      another outcome event. Multistate models are highly relevant for studies of
      patients with cirrhosis; both the classical perception of cirrhosis as either
      compensated or decompensated and the recent, more complex models of cirrhosis
      progression are multistate models. Therefore, researchers who conduct clinical
      studies of patients with cirrhosis must realize that most of their research
      questions assume a multistate disease model. Failure to do so can result in
      severely biased results and bad clinical decisions. The analyses that can be used
      to study disease progression in a multistate disease model may be called
      competing risks analysis, named after the competing risks disease model, which is
      the simplest multistate disease model. In this review article, we introduce
      multistate disease models and competing risks analysis and explain why the
      standard armamentarium of Kaplan-Meier survival estimates and Cox regression
      sometimes gives bad answers to good questions. We also use real data to answer
      typical research questions about the course of cirrhosis and illustrate biases
      resulting from inadequate methods. Finally, we suggest statistical software
      packages that are helpful and accessible to the clinician-researcher.

PMID- 25376656
TI  - Selectivity Mechanism of ATP-Competitive Inhibitors for PKB and PKA.
AB  - Protein kinase B (PKB) acts as a central node on the PI3K kinase pathway.
      Constitutive activation and overexpression of PKB have been identified to involve
      in various cancers. However, protein kinase A (PKA) sharing high homology with
      PKB is essential for metabolic regulation. Therefore, specific targeting on PKB
      is crucial strategy in drug design and development for antitumor. Here, we had
      revealed the selectivity mechanism for PKB inhibitors with molecular dynamics
      simulation and 3D-QSAR methods. Selective inhibitors of PKB could form more
      hydrogen bonds and hydrophobic contacts with PKB than those with PKA. This could
      explain that selective inhibitor M128 is more potent to PKB than to PKA. Then, 3D
      QSAR models were constructed for these selective inhibitors and evaluated by test
      set compounds. 3D-QSAR model comparison of PKB inhibitors and PKA inhibitors
      reveals possible methods to improve the selectivity of inhibitors. These models
      can be used to design new chemical entities and make quantitative prediction of
      the specific selective inhibitors before resorting to in vitro and in vivo
      experiment. 

PMID- 25376657
TI  - Functional assessment of combined reconstruction of the anterior cruciate
      ligament and posterolateral corner with a single femoral tunnel: a two-year
      minimum follow-up.
AB  - PURPOSE: A technique for combined reconstruction of the anterior cruciate
      ligament (ACL) and posterolateral corner (PLC) with a single femoral tunnel was
      recently described. This technique aims to avoid tunnel confluence in the lateral
      femoral condyle. Because there have been no studies on the functional outcomes
      and possible complications of this technique, our goal is to demonstrate a two
      year minimum follow-up of patients who underwent this type of reconstruction.
      METHODS: Nine patients were prospectively evaluated. The ACL was reconstructed
      with an anatomic single bundle, and the PLC structures reconstructed were the
      lateral collateral ligament, the popliteus tendon, and the popliteofibular
      ligament. Patients were evaluated using the objective and subjective
      International Knee Documentation Committee (IKDC) and the Lysholm and Tegner
      scales before and after the surgical procedure. RESULTS: The mean follow-up
      period of the studied patients was 27.3 months. The mean subjective IKDC score
      rose from 43.6 to 84.0, and the Lysholm score rose from 62.1 to 90.8. In the
      final assessment, six patients were classified as IKDC A and three as IKDC B.
      According to the Tegner scale, five patients were able to return to their level
      of activity prior to the injury. There were no reconstruction failures. One
      patient experienced postoperative infection and pain in the lateral scar.
      CONCLUSIONS: The results of the reconstruction of ACL injuries associated with
      PLC with a single femoral tunnel produced a good functional outcome and a low
      incidence of complications.

PMID- 25376658
TI  - Leadership in adolescent health: developing the next generation of maternal child
      health leaders through mentorship.
AB  - Leadership development is a core value of Maternal Child Health Bureau training
      programs. Mentorship, an MCH Leadership Competency, has been shown to positively
      affect career advancement and research productivity. Improving mentorship
      opportunities for junior faculty and trainees may increase pursuit of careers in
      areas such as adolescent health research and facilitate the development of new
      leaders in the field. Using a framework of Developmental Networks, a group of MCH
      Leadership Education in Adolescent Health training program faculty developed a
      pilot mentoring program offered at the Society for Adolescent Health and Medicine
      Annual Meeting (2011-2013). The program matched ten interdisciplinary adolescent
      health fellows and junior faculty with senior mentors at other institutions with
      expertise in the mentee's content area of study in 2011. Participants were
      surveyed over 2 years. Respondents indicated they were "very satisfied" with
      their mentor match, and all agreed or strongly agreed that the mentoring process
      in the session was helpful, and that the mentoring relationships resulted in
      several ongoing collaborations and expanded their Developmental Networks. These
      results demonstrate that MCH programs can apply innovative strategies to
      disseminate the MCH Leadership Competencies to groups beyond MCH-funded training
      programs through programs at scientific meetings. Such innovations may enhance
      the structure of mentoring, further the development of new leaders in the field,
      and expand developmental networks to provide support for MCH professionals
      transitioning to leadership roles.

PMID- 25376659
TI  - IL-10 deficiency increases renal ischemia-reperfusion injury.
AB  - BACKGROUND: Renal ischemia-reperfusion (IR) injury is a frequent cause of acute
      kidney injury, which results in high morbidity and mortality. Inflammation is an
      important factor that is involved in kidney repair after renal IR injury. IL-10
      is a potent anti-inflammatory cytokine that inhibits inflammatory pathways, but
      the role of IL-10 in repairing renal IR injury is not known. Here, we
      investigated the role of IL-10 in kidney repair after renal IR injury. METHODS:
      We used an IL-10(-/-) mouse model and examined the serologic and histomorphology
      of kidney after IR injury. We also measured ki67, TNF-alpha, IL-6, and
      macrophages with immunohistochemistry or Western blotting. RESULTS: There was a
      greater increase in serum creatinine in IL-10(-/-) mice than in wild-type (WT)
      mice. And compared with WT mice, IL-10(-/-) mice had increased histologic renal
      injury and decreased proliferation. Moreover, the expression of TNF-alpha, IL-6
      and macrophages was clearly increased in IL-10(-/-) mice compared with the WT
      mice. CONCLUSION: These data reveal an important role for IL-10 in the
      improvement of renal IR injury, acting through suppression of inflammatory
      mediators, and that IL-10 would be a crucial target for the treatment of IR
      injury.

PMID- 25376660
TI  - Primary subcutaneous myxoid liposarcoma: a clinicopathologic review of three
      cases with molecular confirmation and discussion of the differential diagnosis.
AB  - BACKGROUND: Myxoid liposarcoma typically presents as a deep-seated mass in the
      lower extremity of adults. Presentation as a primary subcutaneous tumor is rare.
      Here we discuss clinicopathologic characteristics of three such cases and their
      differential diagnosis to alert dermatopathologists to this unusual clinical
      presentation of a potentially aggressive entity. METHODS: Cases of myxoid
      liposarcoma were retrieved from archives and consultation files. Inclusion
      required location above the subcutaneous fascia with no evidence of a metastatic
      origin. Clinicopathologic features were retrospectively reviewed. Fluorescence in
      situ hybridization for DDIT3 (CHOP) gene rearrangement was performed on all
      cases. RESULTS: The tumors affected young adults (two males and one female, mean
      36 years, range 32-40 years). No prior history of myxoid liposarcoma or deep soft
      tissue mass was identified. The tumors occurred in the foot, thigh and hand. All
      demonstrated multilobular architecture with abundant myxoid stroma, prominent
      branching capillary vascular network and lipoblastic differentiation. No dermal
      involvement was seen. Round cell features were identified in one case and
      represented <5% of the tumor. All patients remain disease-free following local
      excision only at 6, 8 and 13 months. CONCLUSIONS: Myxoid liposarcoma can rarely
      present as a primary subcutaneous mass and should be considered in the
      differential diagnosis of cutaneous myxoid tumors in adults.

PMID- 25376661
TI  - Urine drug screening: opioid risks preclude complete patient autonomy.

PMID- 25376662
TI  - Non-steroidal anti-inflammatory drug use and essential tremor.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be
      inversely related to Parkinson's disease and Alzheimer's disease, both of which
      may share common mechanisms with essential tremor (ET). Use of these medications
      has not been studied in ET cases vs. controls. OBJECTIVE: To investigate the
      relationships between NSAID (esp. ibuprofen) and aspirin use and ET. METHODS:
      Subjects were enrolled in a case-control study of the environmental epidemiology
      of ET at the Columbia University Medical Center (CUMC; 2009-2014). We compared 92
      ET cases to 107 controls (~1:1 matching) in terms of self-reported NSAID (esp.
      ibuprofen) and aspirin use. RESULTS: The proportion of NSAID or aspirin users
      (current or past) was similar in ET cases and controls (for current user, p =
      0.66; for past user, p = 0.90). Among users, however, the total dosage of
      ibuprofen (frequency in past year * number of tablets taken at a time * typical
      average strength of tablets) was higher in controls than ET cases (p = 0.04). ET
      cases and controls did not differ with respect to aspirin use in the past year.
      CONCLUSION: The proportion of NSAID or aspirin users did not differ in ET cases
      or controls; yet interestingly, ibuprofen use was less in ET cases than in
      controls. The latter raises the possibility that ibuprofen use could have a
      potential protective role in ET.

PMID- 25376663
TI  - MLGO: phylogeny reconstruction and ancestral inference from gene-order data.
AB  - BACKGROUND: The rapid accumulation of whole-genome data has renewed interest in
      the study of using gene-order data for phylogenetic analyses and ancestral
      reconstruction. Current software and web servers typically do not support
      duplication and loss events along with rearrangements. RESULTS: MLGO (Maximum
      Likelihood for Gene-Order Analysis) is a web tool for the reconstruction of
      phylogeny and/or ancestral genomes from gene-order data. MLGO is based on
      likelihood computation and shows advantages over existing methods in terms of
      accuracy, scalability and flexibility. CONCLUSIONS: To the best of our knowledge,
      it is the first web tool for analysis of large-scale genomic changes including
      not only rearrangements but also gene insertions, deletions and duplications. The
      web tool is available from http://www.geneorder.org/server.php .

PMID- 25376664
TI  - Genome-wide gene expression profiles of dental follicle stem cells.
AB  - OBJECTIVE: Dental stem cells (SCs) will be increasingly used for bone
      regeneration in the future. Recently, dental follicle cells (DFCs) from retained
      human third molars have been isolated and characterized as osteogenic
      progenitors. Although these results are promising for regenerative dentistry,
      molecular processes during osteogenic differentiation are not yet well
      understood. MATERIALS AND METHODS: This study compared DFCs before and during
      osteogenic differentiation. ALP activity was measured and cells were stained with
      alizarin red. Real-time RT-PCRs for osteogenic markers were done. The genome-wide
      expression profile was evaluated using a microarray. RESULTS: DFCs showed strong
      mineralization and increased expression of osteogenic marker genes during
      osteogenic differentiation. A microarray analysis showed regulated genes before
      and in the process of osteogenic differentiation (day 7). Several regulated genes
      in DFCs were associated with skeletal development. Bioinformatic analysis
      revealed a number of factors associated with dental follicle osteogenic
      differentiation. Osteogenic differentiation affected expression levels of the
      transcriptional regulators FOXC2 and ZNF219. CONCLUSION: In conclusion, the
      results yielded new objectives for further studies on transcription factors like
      FOXC2 or ETV1 and their role in dental SCs during osteogenic differentiation.

PMID- 25376665
TI  - Bariatric surgery - a dermatologic perspective.
AB  - Bariatric surgery has become a standard option in morbid obesity for patients not
      responding to conventional treatment. A major and stable weight loss can be
      achieved. Since obesity and weight loss may affect skin diseases, we performed
      this review to analyse the impact of bariatric surgery on a number of skin
      diseases. We categorized the skin diseases into three main groups: (i) diseases
      with a possible benefit from bariatric surgery, (ii) diseases that may develop
      after bariatric surgery and (iii) diseases that may persist. We hope that
      dermatologists will achieve an updated knowledge of benefits and possible hazards
      of this type of surgically induced weight loss. 

PMID- 25376666
TI  - Aerobic palladium-catalyzed dioxygenation of alkenes enabled by catalytic
      nitrite.
AB  - Catalytic nitrite was found to enable carbon-oxygen bond-forming reductive
      elimination from unstable alkyl palladium intermediates, providing dioxygenated
      products from alkenes. A variety of functional groups were tolerated, and high
      yields (up to 94 %) were observed with many substrates, also for a multigram
      scale reaction. Nitrogen dioxide, which could form from nitrite under the
      reaction conditions, was demonstrated to be a potential intermediate in the
      catalytic cycle. Furthermore, the reductive elimination event was probed with
      (18) O-labeling experiments, which demonstrated that both oxygen atoms in the
      difunctionalized products were derived from one molecule of acetic acid. 

PMID- 25376668
TI  - Treatment with haemodiafiltration stabilises vascular stiffness (measured by
      aortic pulse wave velocity) compared to haemodialysis.
AB  - BACKGROUND/AIMS: Cerebrovascular diseases such as stroke are increased in
      dialysis patients, and haemodiafiltration has been reported to reduce
      cerebrovascular mortality compared to haemodialysis. We wished to determine
      whether haemodiafiltration improves arterial stiffness. METHODS: We audited
      aortic pulse wave velocity (PWV) measurements 6 months apart in 3 cohorts of
      patients: 69 treated with haemodialysis, 78 who converted from haemodialysis to
      haemodiafiltration and 142 treated with haemodiafiltration. RESULTS: Cohorts were
      well matched for age (means +/- SD: haemodialysis 64 +/- 15 years vs.
      haemodialysis to haemodiafiltration 64 +/- 17 years vs. haemodiafiltration 67 +/-
      16 years), sex (male 65 vs. 59 vs. 63%), diabetes (45 vs. 56.4 vs. 44%) and body
      mass index (26 +/- 6 vs. 26 +/- 5 vs. 26 +/- 5), respectively. Systolic blood
      pressure did not differ over time (haemodialysis 143 +/- 25 vs. 146 +/- 27 mm Hg,
      haemodialysis to haemodiafiltration 153 +/- 26 vs. 154 +/- 25 mm Hg,
      haemodiafiltration 149 +/- 31 vs. 148 +/- 30 mm Hg) or between groups. Aortic PWV
      significantly increased in the haemodialysis group (9.5 +/- 1.9 vs. 10.2 +/- 2.2
      m/s, p < 0.01) and haemodialysis to haemodiafiltration group (9.4 +/- 1.9 vs.
      10.1 +/- 2.2 m/s, p < 0.01), but did not change with haemodiafiltration (9.9 +/-
      2.1 vs. 10.1 +/- 2.2 m/s). CONCLUSIONS: Aortic PWV, a measure of vascular
      stiffness, stabilised with haemodiafiltration. Our preliminary findings require
      further investigation to determine how haemodiafiltration may potentially improve
      vascular stiffness.

PMID- 25376667
TI  - Substantial decreases in the number and diversity of microbiota during
      chemotherapy-induced gastrointestinal mucositis in a rat model.
AB  - PURPOSE: Earlier, we showed in acute myeloid leukemia (AML) patients that the
      microbiota changes dramatically during anticancer treatment, coinciding with
      gastrointestinal mucositis: The commensal anaerobic populations reduce in favor
      of potential pathogens. Therefore, interventions targeting the microbiota during
      mucositis might be interesting but can better be tested in animals than in
      vulnerable mucositis patients. Here, we aimed to study the potential microbial
      changes during methotrexate (MTX)-induced gastrointestinal mucositis in a well
      established rat model and to study whether this model can be used for future
      microbial intervention studies. METHODS: After injection with MTX or saline (day
      0), rats were sacrificed between days 2 and 11. Plasma citrulline level, jejunal
      histology, and the number and diversity of intestinal bacteria in feces (using
      fluorescence in situ hybridization (FISH)) were determined. RESULTS: Mucositis
      was most severe on day 4 when food intake, plasma citrulline, and villus length
      were the lowest, compared with controls (P < 0.0125). At the same time, MTX
      treated rats showed an overall decrease (705-fold) in most bacteria (using a
      universal probe), compared with controls (P < 0.125). Reduced bacterial presence
      was related with the presence of diarrhea and a reduced villus length (rho =
      0.38, P < 0.05). At day 4, there was an absolute and relative decrease of
      anaerobes (13-fold and -58 %, respectively) and streptococci (296-fold and -1 %,
      respectively) but a relative increase of Bacteroides (+49 %), compared with
      controls (P < 0.125). CONCLUSIONS: In the mucositis rat model, we found
      substantial decreases in the number and diversity of microbiota, resembling
      earlier findings in humans. The model therefore seems well suited to study the
      effects of different microbial interventions on mucositis, prior to performing
      human studies.

PMID- 25376669
TI  - The business of accreditation.

PMID- 25376670
TI  - Tri-length laser therapy associated to tecar therapy in the treatment of low-back
      pain in adults: a preliminary report of a prospective case series.
AB  - Low-back pain is very frequent, especially in active adult population. There are
      several different orthopaedic condition that can cause low-back pain, and the
      pain worsen the quality of life significantly. The treatments vary from drugs,
      physical therapies, kinesiology, local infiltrations, and so on. Laser therapy
      has an important role in the treatment of the inflammatory causes of pain, with
      several studies that demonstrate the efficacy of low and high energy laser
      therapy in the treatment of low-back pain. Sixty-six consecutive patients with
      low-back pain with or without leg pain were treated using a combination of Tri
      length laser I-Triax(r) (Mectronic Medicale, Bergamo, Italy) and Pharon(r) tecar
      therapy (Mectronic Medicale, Bergamo, Italy). The patients were treated three
      times a week, every other day, for a total of 10 sessions. Clinical results were
      evaluated using visual analogic scale for individual pain (0 to 10) and the
      Oswestry disability scale (ODS). Tests started before the beginning of therapies
      and 8 weeks after the end of the therapies. Visual analogic scale (VAS) score
      significantly improved from an average value of 8.1 +/- 1.58 pre-treatment to an
      average value 8-weeks post-treatment of 2.63 +/- 2.74 (P < .01). ODS values start
      from a pre-treatment average value of 53.0 +/- 13.0 to a post-treatment average
      value of 23.5 +/- 19.8 (P < .01). A higher improvement both in VAS and in ODS was
      denoted in the group of patient with low-back pain and leg pain (respectively,
      VAS from 8.66 +/- 1.58 to 2.86 +/- 2.94 and ODS from 57.8 +/- 15.5 to 23.7 +/-
      19.5). Low-back pain, associated or not with leg pain, is a very common clinical
      situation. The treatments of this condition are different, and an important role
      can be given to the laser therapy. The conclusion of this study is that the
      association between laser therapy iLux-Triax(r) and tecar therapy Pharon(r) in
      the treatment of low-back pain, with or without leg pain, can significantly
      reduce pain and improve the quality of life in patients with degenerative and
      inflammatory problems.

PMID- 25376673
TI  - Role of the rs6923761 gene variant in glucagon-like peptide 1 receptor gene on
      cardiovascular risk factors and weight loss after biliopancreatic diversion
      surgery.
AB  - BACKGROUND: Studies of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) have
      been directed at identifying polymorphisms in the GLP-1R gene that may be a
      contributing factor in the pathogenesis of obesity. OBJECTIVE: We decided to
      investigate the role of the rs6923761 GLP-1R polymorphism on outcomes after
      biliopancreatic diversion. DESIGN: A sample of 137 morbidly obese patients was
      operated. Weight, blood pressure, basal glucose and lipid profile were measured
      at the basal visit and at each following visit (basal, 3, 9, 12 and 18 months).
      RESULTS: Body mass index, weight and waist circumference were lower in non-A
      allele carriers than A allele carriers 12 and 18 months after surgery. The
      initial weight percent loss at 12 months (45.6 vs. 39.8%; p < 0.05) or 18 months
      (49.6 vs. 41.3%; p < 0.05) was higher in patients with GG genotype than A allele
      carriers. CONCLUSION: Our study showed a higher weight loss 12 and 18 months
      after bariatric surgery in GG variant than A allele carriers. The biochemical
      parameters and cardiovascular comorbidity rates improved similarly in both
      genotypes.

PMID- 25376672
TI  - 'I wouldn't push that further because I don't want to lose her': a
      multiperspective qualitative study of behaviour change for long-term conditions
      in primary care.
AB  - BACKGROUND: Health outcomes for long-term conditions (LTCs) can be improved by
      lifestyle, dietary and condition management-related behaviour change. Primary
      care is an important setting for behaviour change work. Practitioners have
      identified barriers to this work, but there is little evidence examining
      practices of behaviour change in primary care consultations and how patients and
      practitioners perceive these practices. OBJECTIVE: To examine how behaviour
      change is engaged with in primary care consultations for LTCs and investigate how
      behaviour change is perceived by patients and practitioners. DESIGN:
      Multiperspective, longitudinal qualitative research involving six primary health
      care practices in England. Consultations between patients with LTCs and health
      care practitioners were audio-recorded. Semi-structured interviews were completed
      with patients and practitioners, using stimulated recall. Patients were re
      interviewed 3 months later. Framework analysis was applied to all data.
      PARTICIPANTS: Thirty-two people with at least one LTC (chronic obstructive
      pulmonary disease, diabetes, asthma and coronary heart disease) and 10
      practitioners. RESULTS: Behaviour change talk in consultations was rare and, when
      it occurred, was characterized by deflection and diffidence on the part of
      practitioners. Patient motivation tended to be unaddressed. While practitioners
      positioned behaviour change work as outside their remit, patients felt uncertain
      about, yet responsible for, this work. Practitioners raised concerns that this
      work could damage other aspects of care, particularly the patient-practitioner
      relationship. CONCLUSION: Behaviour change work is often deflected or deferred by
      practitioners in consultations, who nevertheless vocalize support for its
      importance in interviews. This discrepancy between practitioners' accounts and
      behaviours needs to be addressed within primary health-care organizations.

PMID- 25376675
TI  - [A proposal for the cutoff point of waist-to-height for the diagnosis of
      metabolic syndrome in children and adolescents in six areas of China].
AB  - OBJECTIVE: This study aimed to determine the optimal cutoff point of Waist-to
      height (WHtR) for the diagnosis of metabolic syndrome (MS) in children and
      adolescents in six areas of China. METHODS: Ninety thousand two hundred and
      eighty four children aged 6 to 15 years old from 6 areas, including Beijing,
      Tianjin, Zhejiang, Shanghai, Chongqing and Nanning in China, were surveyed in a
      random cluster sample. Receiver operating characteristic (ROC) curve analysis was
      employed to determine the optimal cutoff values of WHtR for detecting the
      children and adolescents with two or more risk factors of MS. RESULTS: The
      optimal WHtR cutoff values derived from the ROC analysis was 85(th) and 80(th)
      percentiles in males and females, with 6-15 years of age, respectively. The
      sensitivity and specificity under these cutoff values were 35.78% and 85.41% in
      males and 49.21% and 79.87% in females, for 6-9 years of age, while the
      sensitivity and specificity were 49.60% and 85.90% in males and 47.01% and 80.07%
      in females for 10-15 years of age. The areas under the ROC curves (AUCs) for WHtR
      85(th) percentile were 0.61 and 0.64 in males and females for 6-9 years of age,
      and 0.68 and 0.63 in males and females for 10-15 years of age. The AUCs for WHtR
      85(th) percentile in both genders were significantly larger than that for WHtR
      90(th) percentile for 10-15 years of age. CONCLUSION: Our findings indicated that
      the 85(th) percentile of WHtR (0.48 in both genders for 6-9 years of age, 0.48 in
      males and 0.46 in females for 10-15 years of age) might be an appropriate cutoff
      to predict the children and adolescents with two or more risk factors.

PMID- 25376674
TI  - [Regional differences in patterns of alcohol consumption: findings from the China
      Kadoorie Biobank study on half a million people from 10 regions].
AB  - OBJECTIVE: To describe the regional differences on patterns of alcohol
      consumption across 10 study in the China Kadoorie Biobank (CKB) areas involving
      half a million adults. METHODS: The baseline survey of CKB took place in 5 urban
      and 5 rural areas across China during 2004-2008. Detailed information on alcohol
      consumption of 512 891 participants aged 30-79 years was gathered and analyzed.
      RESULTS: were directly standardized on age (in 10-age groups) and education (5
      groups) structure of the study population for different sex. RESULTS: The overall
      prevalence rates of regular drinking (i.e., at least weekly) were 33.1% among men
      and 2.2% among women. Among men, the prevalence rate was seen highest in Harbin
      (52.0%) and Sichuan (50.2%), but lowest in Gansu (8.1%) and Haikou (18.8%). Most
      regular drinkers in Sichuan, Hunan, and Gansu habitually drank strong spirits (>=
      40% alcohol content), whereas beer was most commonly consumed in Harbin and
      Qingdao, with rice wine most commonly used in the southern regions (Haikou,
      Suzhou,Zhejiang and Liuzhou). Mean alcohol consumption was highest in Sichuan
      (414.6 g/week). Although the mean alcohol consumptions appeared lower on regular
      occasion in Gansu (195.2 g/week) and Henan (239.6 g/week) than in other regions,
      the amount consumed on special occasions in these two regions were the highest
      (Henan:202.3 g/day; Gansu:171.2 g/day). Similar patterns were also seen in women.
      Of all the regular drinkers, 82.6% of men and 56.6% of women reported heavy
      drinking episodes (men: >60 g, women: >40 g) on special occasions. CONCLUSION:
      The patterns of alcohol consumption including prevalence, frequency, amount,
      binge drinking pattern, and type of alcohol beverage varied greatly among the ten
      areas of CKB under study.

PMID- 25376676
TI  - [Cross-sectional association between sedentary behaviors and overweight/obesity
      among children and adolescents in Chengdu, Sichuan].
AB  - OBJECTIVE: To explore the situation of sedentary behavior and how it correlated
      to overweight/obesity among children and adolescents in Chengdu, China. METHODS:
      A total of 2 211 children and adolescents aged 7-15 years old were recruited in
      Chengdu city by using the cluster random sampling method. This was a cross
      sectional study which aimed to collect data on anthropometry including height and
      weight and information on basic characters and sedentary behavior by using a self
      designed questionnaire. RESULTS: According to IOTF criteria, the reporting rate
      of factor as 'watching TV >= 2 hours per day on weekend' showed statistically
      significant differences among normal, overweight and obese groups (34.80% , 4.21%
      and 1.92% respectively, P = 0.016 0) in boys. The reporting rates of 'doing
      homework >= 2 hours per day' were 12.17% , 0.89% and 0.49% respectively (P =
      0.036 0) and statistically different among the three groups, in girls. Similar
      results were obtained in boys based on the WGOC criteria. However, there was no
      statistical difference seen on sedentary behaviors among the three groups in
      girls according to WGOC criteria. After stratified by age groups, rates on
      'watching TV on weekend' were statistically different among normal, overweight
      and obese group in 13-15 age group in girls (P = 0.035 1). Physical activity
      level (PAL)was positively associated with WHR among both boys and girls when
      grouped according to PAL (Schofield). However, it was positively associated with
      WHR only seen in boys according to Chinese Nutrition Society (CNS) criteria.
      CONCLUSION: The reporting rates of sedentary behavior in obese children were
      higher than that in overweight/normal ones. However, the correlation of sedentary
      behaviors on overweight/obesity called for further studies.

PMID- 25376677
TI  - [Study on the appropriate cutoff points of waist-hip-ratio for Kazakh people over
      35 years of age, in Xinjiang].
AB  - OBJECTIVE: The aim of this study was to identify the appropriate cutoffs for
      waist-hip-ratio (WHR) for Kazakh adults at high risk of cardiovascular diseases
      in Xinjiang. METHODS: A Cardiovascular Risk Survey (CRS) study was carried out
      from October 2007 to March 2010, with 14 618 representative participants
      selected, including 4 094 Kazakhs. Complete data on 4 004 participants were
      gathered. The age span of the participants was from 35 to 88 years old with the
      mean age as 48.60 years. Anthropometric data, blood pressure, serum concentration
      of serum total cholesterol, triglyceride, low density lipoprotein cholesterol
      (LDL-C), high density lipoprotein cholesterol (HDL-C) and fasting glucose were
      documented. Prevalence rate, sensitivity, specificity and distance on the
      receiver operating characteristic (ROC) curve of each WHR values were calculated.
      RESULTS: 1) The prevalence rates of hypertension, hypertriglyceridemia were high,
      also with higher WHR seen in both men and women. 2) The prevalence of
      hypercholesterolemia was high with higher WHR seen in women. 3) The shortest
      distances in the receiver operating characteristic curves for hypertension,
      dyslipidemia, diabetes, or >= 2 of these risk factors suggested that the WHR
      cutoffs were 0.92 or 0.91 for men and 0.86 or 0.85 for women. CONCLUSION: Higher
      cutoff for WHR was needed in the identification of patients over 35 at high risk
      of cardiovascular disease among Kazakh population.

PMID- 25376678
TI  - [A cross-sectional study on diabetes among the migrating population in Inner
      Mongolia].
AB  - OBJECTIVE: To investigate the prevalence rates of diabetes and pre-diabetes among
      migrating population in Inner Mongolia. METHODS: Using stratified cluster
      sampling on different industries. Each industry would have the same sample size.
      Questionnaire survey was performed together with anthropometric data gathered and
      laboratory tests completed. RESULTS: The prevalence rates of diabetes and
      impaired glucose regulation (IGR) among the migrating population in Inner
      Mongolia were 12.5% and 12.8% with the age-standardized rate as 9.9% and 9.9%.
      The prevalence of diabetes increased significantly along with the increase of age
      among both males and females (chi2 = 11.162, P = 0.001), but was significantly
      higher in males. The prevalence of IGR in females was significantly higher than
      in males. The prevalence of diabetes among the construction industry workers was
      19.2%, which was the highest among all the industries. The prevalence of diabetes
      was higher in the inter-province pre-migrating group, while the prevalence of IGR
      was increasing along with the duration of migration in the intra-province
      migration group with the trend as chi2 = 9.989, P = 0.002. CONCLUSION: The
      prevalence of diabetes among the migrating population in Inner Mongolia seemed to
      be high, close to the level of urban residents. The prevalence rates of diabetes
      in the population of middle-aged and aged population as well as workers at the
      construction industry were higher than that in the other populations. The
      prevalence of diabetes and IGR among the migration population were related to the
      area where the migration population the in-coming areas Inter-provincial
      migration had a higher contribution to the prevalence of diabetes.

PMID- 25376679
TI  - [Using biomass fuel at home and the development of hypertension in adult women
      living in rural areas of Guangdong: a multilevel model analysis].
AB  - OBJECTIVE: To understand the situation of biomass fuel use in rural Guangdong,
      and how it affecting the prevalence of hypertension in adult women. METHODS:
      Inhabitants aged 18 and above were chosen, using multi-stage stratified cluster
      sampling method from 13 rural countries in Guangdong province in 2010.
      Questionnaire survey and blood pressure measurement were conducted. Multilevel
      logistic regression model was used to study the relationship between biomass fuel
      use and the prevalence of hypertension at both country and individual levels.
      RESULTS: Of the 5794 rural families, 2 569 (44.3%) cooked with biomass fuel in
      the kitchen. 1233 (46.2%) and 1 436 (53.8%) out of the 2669 adult women used
      biomass fuel and clean energy, respectively. Results from chi2 study showed that
      biomass users presented higher prevalence of hypertension (RR = 1.26, 95% CI:
      1.04-1.52), but in multilevel model analysis, the difference was not significant.
      In addition, using an extractor fan when cooking seemed to have protected factor
      in decreasing the risk of hypertension among biomass users (RR = 0.61, 95% CI:
      0.39-0.98). CONCLUSION: Proportion of the use of biomass fuel was still high
      among rural families in Guangdong province. Although there was not enough
      evidence to verify the relationship between the use of biomass fuel and
      hypertension in adult women. However, concerns about the use of biomass fuel
      which causing the indoor air pollution, should be raised.

PMID- 25376680
TI  - [Club-based drug use and its associated risk factors among HIV-positive methadone
      maintenance treatment clients].
AB  - OBJECTIVE: To describe club-based drug use and to explore the determinants on
      those HIV-positive methadone maintenance treatment (MMT) clients. METHODS: This
      study was conducted in 5 MMT clinics in Yunnan province and 612 MMT clients who
      met the survey criteria were recruited for the study. Urine sample was tested as
      a biological marker to identify if heroin, methamphetamine, methylene-dioxy
      methyl-amphetamine, buprenorphine or benzodiazepine had been used. RESULTS: The
      average age among the 612 clients was 38.9 +/- 6.3 years. Among these, 78.9% were
      males, with the average years of education as 8.0 +/- 3.4 years. There were 60.5%
      clients who had good relationship with their families. 153 (25.0%) clients
      reported having used club-related drugs in the last 12 months. Results from the
      urine test showed that the positive rate on morphine was 14.4%, while the
      positive rate for club-related drugs was 26.6%. Factors as residential area,
      casual sexual partners, retention on MMT and occasionally use of heroin were
      associated with urine results on club-related drugs and the prevalence of self
      reported club drug use (P < 0.05). CONCLUSION: Club-related drug use was common
      among HIV-positive MMT clients. Inspection and supervision for club-related drugs
      and the education and intervention programs on related high risk behaviors should
      be strengthened.

PMID- 25376681
TI  - [Study on HIV-1 related genetics and threshold on drug resistance in Dehong
      prefecture of Yunnan province in 2012].
AB  - OBJECTIVE: To study the HIV-1 genotypes and transmitted drug resistance (TDR) in
      Dehong prefecture of Yunnan province in 2012. METHODS: Referring to the
      guidelines for HIV drug resistance threshold survey (HIVDR-TS), 60 plasma samples
      of recently reported HIV-infected individuals between 16 and 25 years old were
      collected in Dehong prefecture from January to August 2012. Genotyping of partial
      pol gene was performed by using reverse transcriptional PCR. HIV-1 genotype and
      the prevalent levels of HIV-1 drug resistance transmission were analyzed.
      RESULTS: 52 plasma samples were successfully sequenced and analyzed. Among them,
      59.6% were Chinese, and the rest (40.4%) were Burmese. Based on pol sequences,
      identified HIV genotypes would include unique recombinant forms (URFs, 38.5%),
      subtype C (34.6%), CRF01_AE (21.2%), CRF08_BC (3.8%), and subtype B (1.9%). One
      drug resistant mutation to non-nucleoside reverse transcriptase inhibitors
      (NNRTIs) was detected in respective two sequences. Based on the statistical
      method of HIVDR-TS, the prevalence of transmitted HIV-1 drug resistance was
      adjusted as a moderate level (5%-15%). CONCLUSION: Diverse HIV-1 genotypes were
      found in this study, and the current HIV-1 drug resistant strains transmission
      was catalogued as moderate prevalence level in Dehong.

PMID- 25376682
TI  - [Current status and associated risk factors of child abuse on children aged 7-12
      in rural areas of Ningxia].
AB  - OBJECTIVE: To describe the current status and associated risk factors on child
      abuse in children aged 7-12 in rural areas of Ningxia. METHODS: Using multistage
      sampling method to select townships and villages. Children aged 7-12 and their
      guardians were selected by random sampling method in those villages. Current
      status on child abuse was described under related percentage while logistic
      regression model was used to evaluate the risk factors associated with child
      abuse. RESULTS: A total number of 704 children aged 7-12 from 15 villages in two
      counties were interviewed. Among them, 359 (50.2%) children had experienced child
      abuse (include physical abuse, negligence, emotional/physical abuse and sexual
      abuse) in the past year. Physical abuse (44.6%) was the most frequent one in all
      the child abuse cases. Only 10 (1.4%) children had a comprehensive understanding
      of 'child abuse'. 55.5% of the children had ever reported this problem to their
      parents or teachers when suffered from abuse episodes. Results from the logistic
      regression model showed that factors as: being boys (OR = 1.37, 95% CI: 1.01
      1.85), under Han nationality (OR = 1.49, 95% CI: 1.06-2.08), at younger age (OR =
      1.16, 95% CI: 1.05-1.28), staying with single parent (OR = 2.05, 95% CI: 1.16
      3.64) and from wealthy family (OR = 1.55, 95% CI: 1.03-2.33) were at risk for
      child abuse. CONCLUSION: Child abuse in rural areas in Ningxia was a serious
      problem, Children's cognitive to child abuse was very low. More attention should
      be paid to children with the following characteristics as: being boys, under Han
      nationality, at younger age, staying with single parent.

PMID- 25376683
TI  - [Molecular typing and surveillance on Salmonella typhimurium strain in Guangdong
      province, 2009-2011].
AB  - OBJECTIVE: To understand the distribution and the characteristics on molecular
      typing of Salmonella (S.) typhimurium isolates gathered from the surveillance
      program and to construct the standard S. typhimurium databank in the laboratory
      through surveillance network PulseNet, in Guangdong province to improve the
      capability of detection on laboratory-based foodborne outbreaks. METHODS: With
      the application of standard pulse-field gel electrophoresis (PFGE) and multiple
      loci VNTR analysis (MLVA) including seven VNTRs loci protocols on PulseNet
      International Network, 275 isolates of S. typhimurium from ten cities in
      Guangdong province were typed and their patterns analyzed. The molecular typing
      databank was constructed by BioNumerics. RESULTS: With S. typhimurium the most
      common serotypes, the average annual positive rate of Salmonella strains and S.
      typhimurium were 4.03% and 1.38% respectively. The positive rate and proportion
      presented a double-peak trend, appearing in May and September. The chromosomal
      DNA of S. typhimurium was digested with Xba I restricted endo-nucleotidase and
      124 PFGE patterns were observed after pulse-field gel electrophoresis, with the
      discrimination index (D) as 0.928 6. The patterns including more than three S.
      typhimurium isolates and were further digested with the second enzyme Bln I to
      achieve 174 patterns, with the D value as 0.989 1. Under MLVA method, 143 variant
      patterns were obtained, with the D value reaching 0.966 5. Data showed that the
      discriminatory ability of the MLVA typing method in S. typhimurium was superior
      to PFGE-Xba I but equal to PFGE-Xba I-Bln I. In addition, when S. typhimurium
      strains were respectively analyzed by PFGE under double enzymes digestion and
      MLVA, the results appeared coincident and relative. CONCLUSION: The variant
      patterns showed by the two molecular typing methods indicating a genetic
      diversity existed among the clinical S. typhimurium isolates in Guangdong
      province. Databank of S. typhimurium was constructed and could be used in
      laboratory surveillance programs. Under the characterization of analyzing
      similarity and evolution among S. typhimurium isolates, MLVA was suitable for
      cluster analysis on early detection of outbreaks caused by S. typhimurium.

PMID- 25376684
TI  - [Spatial and temporal characteristics of human brucellosis, from 2004 to 2012 in
      Shandong province].
AB  - OBJECTIVE: To explore the spatial and temporal characteristics of human
      brucellosis in Shandong province and to provide scientific basis for the
      development of related regional public health strategies. METHODS: 1 802
      diagnosed cases of human brucellosis patients were selected based on the data
      that was collected by Diseases Reporting Information System between year 2004 and
      2012 in Shandong province. Methods on spatial thematic mapping, spatial
      autocorrelation analysis, spatial clustering analysis, and temporal clustering
      analysis were applied to describe the temporal and spatial distribution on human
      brucellosis cases. RESULTS: The incidence rate of human brucellosis increased
      from 0.038 2/100 000 (35 cases) to 0.620 5/100 000 (598 cases), with annual
      average incidence rate as 0.211 1/100 000 and the incidence was evidently
      increased. The value of M (0.375 3) showed that this disease was seasonal, with
      the epidemic months between March and June, accounting for 56.27% (1 014/1 802).
      The Global Moran's I index was 0.198 901 (P = 0.000 120), showing that there was
      a positive correlation between space and the incidence of brucellosis. The
      incidence rates in 2006, 2007, 2009 and 2012 and the space distribution appeared
      a positive correlation (P < 0.05) in Shandong province. The local Moran's I index
      showed that there were 8 "High-High" (HH) clustering areas, which were proved to
      have statistical significance (P < 0.05). Local indicators of spatial association
      (LISA) revealed that southwest and north districts of Shandong were highly
      clustered districts of brucellosis and the areas paralleled to the areas that
      having higher incidence rates. There were two spatial clustering areas in this
      study, one as the center of Juanchen with radiation radius at 33.83 km whose RR
      was 9.78 (P < 0.05) and the other was the center of Binchen with radiation radius
      at 62.78 km with RR as 4.99 (P < 0.05). All the 8 HH counties (districts) were
      included in the two cluster regions. CONCLUSION: Incidence of human brucellosis
      showed an obvious increase in Shandong during year 2004-2012. Months with
      epidemics were between March and June. The incidence of brucellosis in counties
      (districts) was non-randomly distributed. A positive spatial correlation and the
      feature of clusters was noticed.

PMID- 25376685
TI  - [Epidemiological characteristics of typhoid fever and antibiotic susceptibility
      testing of Salmonella Typhi isolates in Guangxi, 1994-2013].
AB  - OBJECTIVE: Through analyzing the typhoid epidemics and to determine and monitor
      regional resistance characteristics of the shift of drug resistant profile on
      Salmonella (S.) Typhi, to understand the related epidemiological characteristics
      of typhoid fever and to provide evidence for the development of strategies, in
      Guangxi. METHODS: Data of typhoid fever from surveillance and reporting system
      between 1994 to 2013 was collected and statistically analyzed epidemiologically.
      The susceptibility of 475 S. Typhi isolates from patients on ten antibiotics was
      tested by broth micro-dilution method and minimum inhibition concentration was
      obtained and interpreted based on the CLSI standard. RESULTS: From 1994 to 2013,
      a total of 57 928 cases of typhoid fever were reported in Guangxi province with
      an annual incidence of 6.29/100 000 and mortality as 0.03%. The higher incidence
      was observed in the population under 20 years of age. There was no significant
      difference on incidence between male and female, but farmers and students were
      among the hardest hit groups. More cases were seen from the northern part of the
      province. Cases appeared all year round with the peak from May to October. A
      total of 13 major outbreaks during 2001 to 2013 were reported and the main
      transmission route was water-borne. All the strains were sensitive to third
      generation cephalosporins cefotaxime and fluoroquinolones norfloxacin. The
      susceptibility rates to tetracycline, chloramphenicol, ampicillin and gentamicin
      was around 98% but relative lower susceptible rate to ciprofloxacin was seen as
      89.89% . The lowest susceptibility was found for streptomycin and
      sulfamethoxazole agents, with the rates as 67.73% and 65.89% , respectively. One
      strain was found to have been resistant to ciprofloxacin and another 47 isolates
      with reduced susceptibility to ciprofloxacin. Twenty eight isolates were found to
      be resistant to multiple antibiotics and one displayed ampicillin,
      chloramphenicol, streptomycin, sulfamethoxazole tetracycline and nalidixic acid
      (ACSSxT-NAL) resistance profile. This was the first report in China. Multi-drug
      resistant strains were frequently isolated from small scale outbreaks of typhoid
      fever. CONCLUSION: The incidence of typhoid fever in Guangxi was still high and
      some strains showed multi-drug resistance and reduced susceptibility to
      ciprofloxacin, indicating that the surveillance and monitor programs on drug
      resistance of S. Typhi should be strengthened, to prevent large scale outbreaks
      of typhoid fever in this province.

PMID- 25376686
TI  - [Analysis on hepatitis C virus infection and related factors among newly reported
      HIV infections in Henan province].
AB  - OBJECTIVE: To study hepatitis C virus infection and related factors among newly
      reported HIV infections in Henan province. METHODS: Both HIV-1 BED incidence and
      anti-HCV tests were applied on newly reported HIV-1 infections between 1 Jul.
      2012 to 30 Jun. 2013 in Henan province. RESULTS: 2049 HIV-1 infections were newly
      reported between 1 July 2012 to 30 June 2013 in Henan province, with the positive
      rate of anti-HCV as 14.87% (271/1 887) and the proportion of BED positives was
      26.34% (497/1 887). The recent HIV-1 infections appeared lower HCV prevalence
      than non-recent HIV-1 infection. Among 20-39 age group, HIV-1 infections had a
      lower HCV prevalence than among the other age groups. Patients carrying HIV-1
      through injecting drug use showed higher HCV prevalence. CONCLUSION: Under
      results on BED; age, infection route and area were influencing factors of HCV
      prevalence in newly reported HIV-1 infections in Henan province, suggesting that
      corresponding prevention programs should be targeted.

PMID- 25376687
TI  - [Isolation and molecular characterization on Abbey Lake Orthobunyavirus
      (Bunyaviridae) in Xinjiang, China].
AB  - OBJECTIVE: To monitor and discover medically important mosquito-borne viruses
      circulating in Xinjiang, China. METHODS: Mosquitoes were collected from Abbey
      Lake wetland in Bortala, in Northern Xinjiang. Viral isolates were obtained
      through inoculating and serial passaging into susceptible mammalian host cells
      (BHK-21), identified by cytopathogenic effect (CPE) observation and plague
      forming assay. Genetic identification of viral isolates was conducted by RT-PCR,
      sequencing and phylogenetic analysis. RESULTS: A virus strain which causing CPE
      on BHK-21 cells, was isolated from the predominant Culex modestus (36.6%) and
      tentatively designated as Abbey Lake virus. Information on molecular
      identification revealed that Abbey Lake virus belonged to Orthobunyavirus genus
      within Bunyaviridae. Partial sequences (651 bp and 980 bp) of viral genomic S and
      M segment showed that Abbey Lake virus was phylogenetically related to Germiston
      virus that uniquely found in South Africa with 90.6% nucleotides and 95.0% amino
      acids similarities in S segment. However, viral M segment displayed much
      variability with 78.6% nucleotides and 86.1% amino acid similarities, suggesting
      a new member of Orthobunyavirus genus was discovered in the area. CONCLUSION: In
      this study, Abbey Lake virus was isolated and characterized indicating its
      potential circulation nature of this newly-emerged mosquito-borne virus.

PMID- 25376688
TI  - [Regional genotyping and the geographical distribution regarding Yersinia pestis
      isolates in China].
AB  - OBJECTIVE: To type Yersinia (Y.) pestis isolates under different regions (DFR)
      and to observe their geographical distributions in China. METHODS: 23 DFRs
      primers and PMT1 (plasmid) primer were used to verify the DFR genomovars of Y.
      pestiss strains from 11 plague foci in China. A total of 3 044 Y. pestis isolates
      were involved for analysis on DFR profiles with the characteristics of
      geographical distribution. RESULTS: 52 genomovars were verified in 3 044 Y.
      pestis strains in China in which 19 genomovars as major and 33 genomovars as
      minor genomovar. 21 new genomovars, namely genomovar 32 to genomovar 52 were
      described on the basis of 31 genomovars previously confirmed. Three new
      genomovars belonged to new major genomovars, namely Himalayan marmot natural
      plague foci of the Qinghai-Tibet plateau newly added genomovar 32 and genomovar
      44 as major genomovars. Mongolian gerbil natural plague foci of Inner Mongolia
      plateau were newly added genomovar 50 as one of the major genomovars. CONCLUSION:
      Among 21 new genomovars, 3 were major genomovars, with Chinese Y. pestis DFR as
      the major genomovars which had obvious distribution characteristics.

PMID- 25376689
TI  - [Safety and immunogenicity of seasonal inactivated influenza vaccine (split
      virion) and cross-reactive antibody responses to the H7N9 avian influenza virus].
AB  - OBJECTIVE: To evaluate the safety and immunogenicity of seasonal inactivated
      influenza vaccine (split virion) and to analyze its cross-reactive antibody
      responses to H7N9 avian influenza virus. METHODS: An open-labeled clinical trial
      was carried out in infants aged 6-35 months, adults aged 18-60 years and the
      elderly aged >60 years. After vaccinations (one dose for adults and the elderly
      and two doses for infants), adverse events were observed. Serum samples were
      obtained before vaccination and 21 days after vaccination from adults and elderly
      subjects. Three types of antibody against seasonal influenza virus and antibody
      against H7N9 avian influenza virus were tested using microhemagglutination
      inhibition (HI) assay. Immunogenicity of the vaccine was evaluated based on the
      immunogenicity criteria for adults and the elderly, set by the Committee for
      Medicinal Products for Human Use (CHMP) for the European Medicines Agency.
      RESULTS: A total of 202 subjects (65 infants, 69 adults and 68 elderly) were
      enrolled and injected for at least one dose. The overall rate of adverse events
      was 12.4% (25/202) and most of them were under systemic reaction. No serious
      adverse event was reported. Pre- and post-vaccination serum samples were
      collected from 124 subjects (64 adults, 60 elderly). After 21 days of
      vaccination, the sero-conversion rate, sero-protection rate, and geometric mean
      titer (GMT) ratio (post-/pre-vaccination) of antibody against seasonal influenza
      virus were 78.1%-90.6%, 92.2%-100.0% and 7.9-41.0 among adults while 66.7%-83.3%,
      86.7%-100.0% and 5.7-20.4 among the elderly, respectively. However, after
      vaccination, both sero-conversion rate and sero-protection rate of antibody
      against H7N9 avian influenza virus among adults and the elderly became zero, with
      GMT ratio between 1.2 and 1.4. CONCLUSION: This trial vaccine appeared to have
      good safety and immunogenicity but inducing no cross-reactive antibody response
      to H7N9 avian influenza virus.

PMID- 25376690
TI  - [Recognizing the vaccination strategy of pertussis according to the family
      aggregation feature of transmission].
AB  - OBJECTIVE: To understand the age distribution of pertussis patients admitted in
      the children hospital and to analyze the source of infection as well as its
      transmission patterns. METHODS: Patients visiting to the Children Hospital and
      epidemiologically related cases during Feb. 2012 to Aug. 2013 were tested to
      confirm the diagnosis. Excel 2007 software was used to analyze the age
      distribution and clinical symptoms of clinic cases, the source of infection or
      subsequent cases. RESULTS: 165 out of 254 clinically suspicious pertussis cases
      and 38 out of the 54 epidemiologically related cases were confirmed of having
      pertussis infection. There were 138 (83.6%) cases under 1 year of age in the
      confirmed clinical cases and 36 (94.7%) cases older than 20 years of age among
      the confirmed epidemiologically related pertussis cases. All the confirmed
      epidemiologically related cases were misdiagnosed or missed for diagnosis. As the
      source of pertussis infection in confirmed clinical cases, parents played an
      imported role among 25 of the 32 cases. Transmission from infants and/or little
      children to adults were also observed in this study. CONCLUSION: Infants
      accounted for the most among the pertussis patients that visiting the clinics.
      Adults, being misdiagnosed or missed diagnosed, were the main sources of
      infection to infants. Epidemics of pertussis occurred under family aggregation.
      Further study was in need to develop the proper strategy for pertussis booster
      vaccination.

PMID- 25376691
TI  - [Impact of isolated diastolic hypertension on new-onset cardiovascular and
      cerebro-vascular diseases].
AB  - OBJECTIVE: To explore the impact of isolated diastolic hypertension (IDH) on new
      onset cardio-cerebral vascular diseases (CVD). METHODS: This cohort study
      involved 101 510 participants who were employees of the Kailuan Group-a state-run
      coal mining company, in 2006 and 2007. Among them, 6 780 subjects were diagnosed
      with IDH, 35 448 subjects were diagnosed with high-normal blood pressure and 19
      460 subjects were diagnosed with normal tension. However, none of them had the
      history of either cardio-cerebral vascular disease or malignant cancer. Cardio
      cerebral vascular events including cerebral infarction, cerebral hemorrhage,
      acute myocardial infarction were recorded every 6 months during the follow-up
      (47.1 +/- 4.8) period. Multivariable Cox proportional hazards regression models
      were used to analyze the risk factors of first-ever CVD events. RESULTS: 1) There
      were 675 CVD events occurred during the follow-up period. The incidence rates of
      CVD events (1.7% vs. 0.9%), cerebral infarction (1.0% vs. 0.6%) and cerebral
      hemorrhage (0.4% vs. 0.1%) were significantly higher in IDH group than that in
      the normal tension group (all P < 0.05). 2) After adjustment for other
      established CVD risk factors, the hazards ratios became 1.67 (95% CI: 1.28-2.17)
      for total CVD events and 1.59 (95% CI: 1.12-2.27) for cerebral infarction and
      2.67 (95% CI: 1.54-4.65) for cerebral hemorrhage in the IDH group. 3). In
      stratified analysis on age, after adjustment for other established CVD risk
      factors, the hazards ratio was 2.22 (95% CI: 1.41-3.50) for cerebral infarction
      in lower 60 years old group, while the it was 7.27 (95% CI: 2.58-20.42) for
      cerebral hemorrhage in groups older than 60 years of age. CONCLUSION: IDH was the
      independent risk factor for the total cardio-cerebral vascular events, on both
      cerebral infarction and cerebral hemorrhage. The predicted values of IDH for
      different CVD events were diverse on different age groups.

PMID- 25376692
TI  - [Chinese guidelines for data processing and analysis concerning the International
      Physical Activity Questionnaire].
AB  - To introduce standard methods of scoring the data derived from both short and
      long form instruments of the International Physical Activity Questionnaire
      (IPAQ). The introduction part consists of a set of domains which include the
      structure of questionnaire, principles of data cleaning, calculation methods and
      grouping rules. Through practical experience, a specific calculation process of
      IPAQ-long based on the standard methods was showed. 

PMID- 25376693
TI  - [The association of occupational exposure to extremely low frequency
      electromagnetic fields and the risk of neurodegenerative diseases].

PMID- 25376694
TI  - [Prevalence, prevention and treatment of human monocytic ehrlichiosis in China].

PMID- 25376696
TI  - Supramolecular copolymers obtained from two-component gels: metal ion-mediated
      cross-linking, enhanced viscoelasticity and supramolecular yarns.
AB  - The hydrogels based on the co-assembly of bolaamphiphilic L-histidine and 2,2'
      bipyridine-dicarboxylic acids were transformed into viscoelastic supramolecular
      polymers by cross-linking with Cu(II) ions, and macroscopic supramolecular yarns
      were obtained by direct drawing from a dilute aqueous solution of the
      supramolecular polymers.

PMID- 25376695
TI  - Intranasal steroid injections and blindness: our personal experience and a review
      of the past 60 years.
AB  - OBJECTIVES/HYPOTHESIS: To assess for the safety of intranasal steroid injections.
      STUDY DESIGN: Retrospective chart review and review of the medical literature.
      METHODS: Seventy-eight patients with chronic rhinitis or sinusitis underwent 237
      intraturbinate or intrapolyp triamcinolone acetonide injections between April
      2008 and June 2013 at a single, private, outpatient otolaryngology clinic. A
      retrospective chart review was performed to evaluate for treatment complications,
      symptom improvement, and demographic data. A PubMed literature search was
      performed for all case series extracting the incidence of visual complications
      following intranasal steroid injections. All published reports of visual
      complications from these series and independent case reports were compiled and
      analyzed. RESULTS: Of the 237 injections performed, 152 were intraturbinate and
      85 were intrapolyp. One of the intrapolyp injections resulted in a transient
      visual change that resolved spontaneously. Nine other case series meeting the
      search criteria were found. Of the reported 117,669 injections performed, three
      resulted in visual complications yielding an estimated visual complication rate
      of 0.003%. All three of these events resolved spontaneously and resulted in no
      permanent visual deficits. A total of 19 reports of visual complications
      following intranasal steroid injections were discovered. Of these, the majority
      have insufficient detail regarding the injection technique or cite gross
      deviation from the correct injection protocol. CONCLUSION: Intranasal steroid
      injections are a safe treatment for chronic rhinitis and sinusitis patients. When
      performed correctly, there is evidence to justify the use of methylprednisolone
      acetate or triamcinolone acetonide injections into the inferior turbinates and
      nasal polyps.

PMID- 25376697
TI  - Microfluidic chip with thermoresponsive boronate affinity for the capture-release
      of cis-diol biomolecules.
AB  - The polydimethylsiloxane microfluidic chip grafted with poly(N
      isopropylacrylamide-3-acrylamidephenylboronic acid) (P(NIPAAm-co-AAPBA)) was
      fabricated by UV-induced grafting polymerization for the capture-release of cis
      diol-containing biomolecules by temperature-modulated changes instead of changing
      the pH value of the mobile phase. Based on the optimal time for benzophenone
      soaking and UV irradiation of grafting polymerization, P(NIPAAm-co-AAPBA) was
      successfully grafted on the polydimethylsiloxane substrates, which were
      characterized by scanning electron microscopy, water contact angle measurements,
      and Fourier transform infrared spectroscopy. The P(NIPAAm-co-AAPBA)-grafted
      polydimethylsiloxane microfluidic chip can be successfully used for the capture
      and release of cis-diol-containing adenosine by adjusting the temperature from 4
      to 55 degrees C, and the result was validated by Triple Quad liquid
      chromatography with mass spectrometry. With further development, the fabricated
      polydimethylsiloxane microfluidic chips might be chosen as a potential tool for
      the capture and release of cis-diol-containing macromolecules, such as
      horseradish peroxidase and glycoprotein. 

PMID- 25376698
TI  - Electronically active impurities in colloidal quantum dot solids.
AB  - Colloidal quantum dot films have seen rapid progress as active materials in
      photodetection, light emission, and photovoltaics. Their processing from the
      solution phase makes them an attractive option for these applications due to the
      expected cost reductions associated with liquid-phase material deposition.
      Colloidally stable nanoparticles capped using long, insulating aliphatic ligands
      are used to form semiconducting, insoluble films via a solid-state ligand
      exchange in which the original ligands are replaced with short bifunctional
      ligands. Here we show that this ligand exchange can have unintended and undesired
      side effects: a high molecular weight complex can form, containing both lead
      oleate and the shorter conductive ligand, and this poorly soluble complex can end
      up embedded within the colloidal quantum dot (CQD) active layer. We further show
      that, by adding an acidic treatment during film processing, we can break up and
      wash away these complexes, producing a higher quality CQD solid. The improved
      material leads to photovoltaic devices with reduced series resistance and
      enhanced fill factor relative to controls employing previously reported CQD
      solids. 

PMID- 25376699
TI  - Safety and efficacy outcomes in patients undergoing pulmonary vein isolation with
      second-generation cryoballoon?.
AB  - AIMS: The second-generation cryoballoon (Arctic Front AdvanceTM) (Arc-Adv-CB) has
      a redesigned injection system which distributes the refrigerant homogenously to
      the frontal balloon surface. The aim of this study was to compare the efficacy
      and safety of the Arc-Adv-CB and its predecessor (Arctic FrontTM) (Arc-CB) in
      patients who underwent pulmonary vein isolation (PVI) for atrial fibrillation
      (AF). METHODS AND RESULTS: Three hundred and six patients (55.35 +/- 10.60 years,
      47.05% male) were included in the study. A total of 1205 pulmonary veins were
      attempted for PVI with either Arc-CB or Arc-Adv-CB. The follow-up durations were
      30 (23-38) and 10 (8-13) months in Arc-CB and Arc-Adv-CB groups, respectively (P
      < 0.001). When the blanking period was considered, freedom from AF after a single
      ablation procedure was 68.53 and 90.83% in patients undergoing PVI with Arc-CB
      and Arc-Adv-CB, respectively. The most frequent complication was transient
      phrenic nerve palsy (PNP) which occurred in five(2.54%) and nine(8.26%) of
      patients undergoing PVI with Arc-CB and Arc-Adv-CB, respectively (P = 0.040).
      Left atrial (LA) diameter (hazard ratio, HR: 3.552, 95% CI: 2.034-6.201, P <
      0.001), smoking history (HR:1.643, 95% CI: 1.011-2.671, P = 0.045), persistent AF
      (HR:1.725, 95% CI: 1.021-2.915, P = 0.041), duration of AF (HR:1.039, 95% CI:
      1.000-1.080, P = 0.047), and early AF recurrence (HR:2.399, 95% CI: 1.443-3.989,
      P < 0.001) were associated with increased late AF recurrence. On the other hand,
      intraprocedural vagal reactions (HR: 0.550, 95% CI: 0.331-0.915, P = 0.021) and
      Arc-Adv-CB use (HR: 0.441, 95% CI: 0.225-0.866, P = 0.017) were associated with
      lower late AF recurrence. Left atrial diameter (HR: 3.072, 95% CI: 1.646-5.732, P
      < 0.001), early AF recurrence (HR: 1.906, 95% CI: 1.103-3.291, P = 0.021), and
      Arc-Adv-CB use (HR: 0.472, 95% CI: 0.239-0.931, P = 0.030) were independent
      predictors for late AF recurrence. CONCLUSION: Our study has shown that Arc-Adv
      CB use is associated with lower late AF recurrences at the cost of an increased
      risk for PNP.

PMID- 25376700
TI  - MicroRNA-21 and the clinical outcomes of various carcinomas: a systematic review
      and meta-analysis.
AB  - BACKGROUND: MicroRNA-21 (miR-21) has been suggested to play a significant role in
      the prognosis of carcinoma. The recognition of novel biomarkers for the
      prediction of cancer outcomes is urgently required. However, the potential
      prognostic value of miR-21 in various types of human malignancy remains
      controversial. The present meta-analysis summarises and analyses the associations
      between miR-21 status and overall survival (OS) in a variety of tumours. METHODS:
      Eligible published studies were identified by searching the PubMed and Chinese
      Biomedicine databases. The patients' clinical characteristics and survival
      results were pooled, and a pooled hazard ratio (HR) with 95% confidence intervals
      (95% CI) was used to calculate the strength of this association. A random-effects
      model was adopted, and then, meta-regression and subgroup analyses were
      performed. In addition, an analysis of publication bias was also conducted.
      RESULTS: Twenty-seven eligible articles (including 31 studies) were identified
      that included survival data for 3273 patients. The pooled HR suggested that high
      miR-21 was clearly related to worse overall survival (HR = 2.27, 95% CI: 1.81
      2.86), with a heterogeneity measure index of I2 = 76.0%, p = 0.001, showing that
      miR-21 might be a considerable prognostic factor for poor survival in cancer
      patients. CONCLUSIONS: MiR-21 might be a potentially useful biomarker for
      predicting cancer prognosis in future clinical applications.

PMID- 25376702
TI  - Determination of fourteen sunscreen agents in cosmetics using high-performance
      liquid chromatography.
AB  - OBJECTIVE: Commercial sunscreens consist of various compounds ranging from
      inorganic mineral pigments to organic chemical absorbents to achieve the required
      degree of protection against sunlight. However, the UV radiation screening
      ingredients have side effects. In this study, therefore, to ensure compliance
      with the maximum permissible chemical concentrations in sunscreen cosmetic
      products, a simultaneous and improved determination method for sunscreen
      chemicals was assessed. METHODS: Waters 2690 separations module HPLC system
      equipped with a Waters 486 tunable absorbance detector (UV-visible detector) has
      been employed and optimized to detect 14 compounds. For the separation, a Waters
      C18 column (5 MUm, 4.6 mm i.d. 150 mm) and 1% of 0.1 M phosphoric acid in ethanol
      (solvent A) and in distilled water (solvent B) as mobile phases were used.
      RESULTS: The correlation coefficients of 14 standard mixture solutions exceeded
      0.9993 in the range 2.5-200 MUg mL(-1). The intra- and interday recovery and
      precision (relative standard deviation) of the method were 90.91-109.98% and
      within 10%, respectively, indicating that the developed method could provide
      reliable, precise and reproducible data. The detection limit was determined to be
      0.01-1.99 MUg mL(-1), and the quantization limit was determined to be 0.02-6.02
      MUg mL(-1), which were relatively lower than previous studies. CONCLUSION: This
      method was highly optimized in terms of selectivity, reproducibility and
      efficiency for the detection of 14 compounds. The validation data indicated that
      the improved method was quite suitable for their quantitative analysis of
      commercial product samples. Therefore, this method was applied to the
      determination of 14 compounds in commercial sunscreen cosmetic products. We
      verified that the amounts of sunscreen ingredients in the five currently sold
      sunscreens were >0.5% and within the designated limit, which means those could
      produce the safe and desired sunscreen effects on the skin. The present method
      could be applied to effectively monitor the process management and quality
      control of the cosmetics that are sold in the market.

PMID- 25376701
TI  - Diagnosis and Treatment of Low Testosterone among Patients with End-Stage Renal
      Disease.
AB  - The prevalence of low testosterone level is particularly high among patients with
      end-stage renal disease (ESRD) and has been associated with mortality. In
      populations without ESRD, low testosterone level has also been associated with a
      number of morbidities including cardiovascular disease, diabetes mellitus, low
      muscle mass, low bone mass, low physical performance, and frailty. However, there
      is controversy regarding what constitutes low testosterone level in the aging
      population and at what level replacement therapy with testosterone is indicated.
      There are no randomized controlled trials investigating long-term outcomes of
      testosterone replacement therapy in populations with or without ESRD. Available
      trial results suggest equivocal improvements in sexual function. Muscle mass and
      bone mineral density appear to improve, but results in physical function and
      performance are mixed and there are no data on fracture prevention. Some recent
      data suggest harm when testosterone was given to men with limited mobility.
      Finally, there is little evidence that testosterone adds to existing
      erythropoietin agents in the treatment of anemia in ESRD. Due to lack of evidence
      supporting long-term use of testosterone, the authors recommend against the
      routine use of testosterone in ESRD patients with low testosterone levels.
      Testosterone treatment can be considered in those with low bone mass and total
      testosterone level <200 ng/dl, or in younger patients with sexual complaints with
      total testosterone level lower than the reference range. It is important to
      engage patients in discussion of risks and benefits before initiating
      testosterone therapy; testosterone therapy should be discontinued if the intended
      treatment effect is not observed after short-term use. 

PMID- 25376703
TI  - Heart pigmentation in the gray bichir, Polypterus senegalus (Actinopterygii:
      Polypteriformes).
AB  - The occurrence of pigment cells in the heart is well documented in amphibians,
      birds and mammals. By contrast, information on heart pigmentation in fish is
      extremely sparse. The aim is to report the presence of pigment cells over the
      entire surface of the heart in the gray bichir, Polypterus senegalus. The sample
      consisted of 12 hearts, which, after gross anatomical examination, were studied
      using histochemical and immunohistochemical techniques for light microscopy, and
      transmission electron microscopy. The pigment cells were located in the
      subepicardium, showing a regular distribution pattern across the whole heart,
      except for the anterior end of the outflow tract, where the pigmentation was much
      more intense. The cells contained dark, ovoid-shaped organelles which was
      consistent with a melanosome cell identity. As in other vertebrates, the
      physiological role of the pigment cells in the heart of the gray bichir is
      unknown. The absence of such cells in hearts of other polypteriforms suggests
      that cells containing melanin are not essential for normal fish heart function.
      Basing on literature data concerning tetrapods, it can be inferred that the
      pigment cells of the heart of the gray bichir derive from the neural crest. If
      this were true, our findings would provide the first evidence for the presence of
      neural crest-derived cells in the subepicardium of adult hearts of early
      actinopterygians. 

PMID- 25376704
TI  - N-Boc deprotection and isolation method for water-soluble zwitterionic compounds.
AB  - A highly efficient TMSI-mediated deprotection and direct isolation method to
      obtain zwitterionic compounds from the corresponding N-Boc derivatives has been
      developed. This method has been demonstrated in the final deprotection/isolation
      of the beta-lactamase inhibitor MK-7655 as a part of its manufacturing process.
      Further application of this process toward other zwitterionic compounds, such as
      dipeptides and tripeptides, has been successfully developed. Furthermore, a
      catalytic version of this transformation has been demonstrated in the presence of
      BSA or BSTFA. 

PMID- 25376705
TI  - Tumour characteristics, treatment patterns and survival of patients aged 80 years
      or older with colorectal cancer.
AB  - AIM: This study aimed to clarify tumour characteristics and treatment patterns
      for patients with colorectal cancer aged 80 years or older and the impact of age
      on survival using a large-scale cancer registry database. METHOD: The database
      was used to identify 40 851 colorectal cancer patients who underwent surgery
      between 1995 and 2004. Patients were stratified into four age groups (< 50, 50
      64, 65-79, >= 80 years). Demographics, tumour characteristics, treatment pattern
      and survival were compared between age groups. Additionally, the impact of lymph
      node dissection and adjuvant chemotherapy on survival was studied using the
      propensity score-matching method. RESULTS: In the over 80 age group, patients
      were more commonly female, with right colon cancer, multiple primary cancers,
      history of colorectal cancer, high serum carcinoembryonic antigen values, large
      tumour, undifferentiated histology, and more frequent pT3/pT4 tumours. In
      contrast, metastatic disease, central lymph node dissection and adjuvant
      chemotherapy were less frequent. Overall survival and cancer-specific survival
      decreased with increasing age for any stage. Multivariate analysis showed age to
      be an independent predictor of overall survival (hazard ratio 1.45, 95% CI 1.34
      1.58, P < 0.001). In the propensity score-matched cohort, overall survival of the
      patients with central node dissection and having adjuvant chemotherapy was
      significantly better than for those without. This difference was not
      statistically significant in patients aged 80 and above. CONCLUSION: This study
      showed a significant difference in tumour characteristics and treatment patterns
      in patients aged 80 and above. Even after adjustment for clinicopathological
      factors, the difference in survival persisted and age was considered a robust
      prognostic factor.

PMID- 25376706
TI  - Titania nanotube arrays for local drug delivery: recent advances and
      perspectives.
AB  - INTRODUCTION: Titania nanotube (TNTs) arrays engineered by simple and scalable
      electrochemical anodization process have been extensively explored as a new
      nanoengineering approach to address the limitations of systemic drug
      administration. Due to their outstanding properties and excellent
      biocompatibility, TNTs arrays have been used to develop new drug-releasing
      implants (DRI) for emerging therapies based on localized drug delivery (DD). This
      review highlights the concepts of DRI based on TNTs with a focus on recent
      progress in their development and future perspectives towards advanced medical
      therapies. AREAS COVERED: Recent progress in new strategies for controlling drug
      release from TNTs arrays aimed at designing TNTs-based DRI with optimized
      performances, including extended drug release and zero-order release kinetics and
      remotely activated release are described. Furthermore, significant progress in
      biocompatibility studies on TNTs and their outstanding properties to promote
      hydroxyapatite and bone cells growths and to differentiate stem cells are
      highlighted. Examples of ex vivo and in vivo studies of drug-loaded TNTs are
      shown to confirm the practical and potential applicability of TNTs-based DRI for
      clinical studies. Finally, selected examples of preliminary clinical applications
      of TNTs for bone therapy and orthopedic implants, cardiovascular stents,
      dentistry and cancer therapy are presented. EXPERT OPINION: As current studies
      have demonstrated, TNTs are a remarkable material that could potentially
      revolutionize localized DD therapies, especially in areas of orthopedics and
      localized chemotherapy. However, more extensive ex vivo and in vivo studies
      should be carried out before TNTs-based DRI could become a feasible technology
      for real-life clinical applications. This will imply the implementation of
      different approaches to overcome some technical and commercial challenges.

PMID- 25376707
TI  - Autotaxin-LPA axis regulates hMSC migration by adherent junction disruption and
      cytoskeletal rearrangement via LPAR1/3-dependent PKC/GSK3beta/beta-catenin and
      PKC/Rho GTPase pathways.
AB  - Bioactive molecules and stem cell-based regenerative engineering is emerging a
      promising approach for regenerating tissues. Autotaxin (ATX) is a key enzyme that
      regulates lysophosphatidic acid (LPA) levels in biological fluids, which exerts a
      wide range of cellular functions. However, the biological role of ATX in human
      umbilical cord blood-derived mesenchymal stem cells (hMSCs) migration remains to
      be fully elucidated. In this study, we observed that hMSCs, which were stimulated
      with LPA, accelerated wound healing, and LPA increased the migration of hMSCs
      into a wound site in a mouse skin wound healing model. In an experiment to
      investigate the effect of LPA on hMSC migration, ATX and LPA increased hMSC
      migration in a dose-dependent manner, and LPA receptor 1/3 siRNA transfections
      inhibited the ATX-induced cell migration. Furthermore, LPA increased Ca(2+)
      influx and PKC phosphorylation, which were blocked by Galphai and Galphaq
      knockdown as well as by Ptx pretreatment. LPA increased GSK3beta phosphorylation
      and beta-catenin activation. LPA induced the cytosol to nuclear translocation of
      beta-catenin, which was inhibited by PKC inhibitors. LPA stimulated the binding
      of beta-catenin on the E-box located in the promoter of the CDH-1 gene and
      decreased CDH-1 promoter activity. In addition, the ATX and LPA-induced increase
      in hMSC migration was blocked by beta-catenin siRNA transfection. LPA-induced PKC
      phosphorylation is also involved in Rac1 and CDC42 activation, and Rac1 and CDC42
      knockdown abolished LPA-induced F-actin reorganization. In conclusion, ATX/LPA
      stimulates the migration of hMSCs through LPAR1/3-dependent E-cadherin reduction
      and cytoskeletal rearrangement via PKC/GSK3beta/beta-catenin and PKC/Rho GTPase
      pathways.

PMID- 25376709
TI  - Agenesis of the superior cornua of the thyroid cartilage: a rare variant of
      medicolegal importance.
AB  - It is important that forensic pathologists are familiar with variations in the
      size and shape of the laryngohyoid complex when interpreting injuries and
      pathology of the head and neck region. Accurate postmortem examination of the
      laryngohyoid structures may be difficult if anatomical variation in these
      structures is present. Agenesis of the upper horns of the thyroid cartilage has
      medicolegal significance because it may be mistaken for a fracture or other
      trauma-related conditions. We present 3 cases with different forms of agenesis of
      the superior cornu of the thyroid cartilage, namely, right unilateral, left
      unilateral, and bilateral agenesis. 

PMID- 25376710
TI  - An unusual autopsy case of cytokine storm-derived influenza-associated
      encephalopathy without typical histopathological findings: autopsy case report.
AB  - Cytokine storm-derived influenza-associated encephalopathy is a severe
      complication, affecting not only the brain but also multiple systemic organs
      including the heart and lungs. Hundreds of Japanese children are afflicted by
      influenza-associated encephalopathy every year. Influenza-associated
      encephalopathy can be diagnosed by pathological changes, such as advanced brain
      edema and disruption of astrocytic projections, which is known as
      clasmatodendrosis. In the present case, despite the absence of significant
      histopathological findings in the brain, the diagnosis of influenza-associated
      encephalopathy was made on the basis of autopsy findings such as brain swelling,
      pathological findings including diffuse alveolar damage, and increase in the
      concentrations of interleukin-6 in both the serum and cerebrospinal fluid. In
      this case, the interval from high fever to death was approximately 7 hours and
      may have been too short for histopathological features to develop. This is an
      unusual autopsy case of cytokine storm-derived influenza-associated
      encephalopathy without typical histopathological findings. 

PMID- 25376708
TI  - Virotherapy targeting cyclin E overexpression in tumors with adenovirus-enhanced
      cancer-selective promoter.
AB  - Oncolytic virotherapy can selectively destroy cancer cells and is a potential
      approach in cancer treatment. A strategy to increase tumor-specific selectivity
      is to control the expression of a key regulatory viral gene with a tumor-specific
      promoter. We have previously found that cyclin E expression is augmented in
      cancer cells after adenovirus (Ad) infection. Thus, the cyclin E promoter that is
      further activated by Ad in cancer cells may have unique properties for enhancing
      oncolytic viral replication. We have shown that high levels of viral E1a gene
      expression are achieved in cancer cells infected with Ad-cycE, in which the
      endogenous Ad E1a promoter was replaced with the cyclin E promoter. Ad-cycE shows
      markedly selective oncolytic efficacy in vitro and destroys various types of
      cancer cells, including those resistant to ONYX-015/dl1520. Furthermore, Ad-cycE
      shows a strong capacity to repress A549 xenograft tumor growth in nude mice and
      significantly prolongs survival. This study suggests the potential of Ad-cycE in
      cancer therapy and indicates the advantages of using promoters that can be
      upregulated by virus infection in cancer cells in development of oncolytic
      viruses. Key messages: Cyclin E promoter activity is high in cancer cells and
      enhanced by adenovirus infection. Cyclin E promoter is used to control the E1a
      gene of a tumor-specific oncolytic adenovirus. Ad-cycE efficiently targets cancer
      cells and induces oncolysis. Ad-cycE significantly repressed xenograft tumor and
      prolonged survival.

PMID- 25376711
TI  - Lethal pulmonary air embolism caused by the removal of a double-lumen
      hemodialysis catheter.
AB  - Pulmonary air embolisms due to the removal of a central venous catheter are rare,
      but catheter removal is known to be a high risk factor for air embolism. In
      particular, the removal of a large catheter, such as a double-lumen hemodialysis
      catheter, can allow a large amount of air to enter into the bloodstream, which
      often results in sudden death. So, during catheter removal, special care should
      be taken to prevent air from entering blood vessels, for example, to ensure that
      the patient's head is tilted downward, that they have inhaled and are holding
      their breath, and that a covering gauze and inert ointment have been applied to
      the exit site. We report a lethal case of pulmonary air embolism caused by the
      removal of a double-lumen catheter from the right internal jugular vein of a
      patient who was sitting up and had not been instructed to hold their breath. 

PMID- 25376712
TI  - Association between household income and the outcome of arthroplasty: a register
      based study of total hip and knee replacements.
AB  - INTRODUCTION: Previous research findings regarding the association between the
      outcomes of total hip and knee arthroplasty and patients' socioeconomic status
      have been contradictory. Consequently, we wanted to analyse whether individual
      level household income was associated with the risk of revision arthroplasty and
      whether the time span in days from the primary arthroplasty to the revision
      operation varied according to income quintile. MATERIALS AND METHODS: All first
      total hip and knee arthroplasties performed due to primary osteoarthritis in
      Finland from 1998 to 2007 were included in the study. Cox proportional hazard
      regression modelling was applied in the analysis regarding the risk of revision
      after the primary operation, while Poisson regression modelling was applied in
      the analysis regarding differences in the time from the primary to the revision
      operation between income quintiles. RESULTS: The relationship between household
      income and the risk of revision arthroplasty was not statistically significant.
      The relationship remained insignificant, even when age, sex, and other
      confounding factors were adjusted for or analyses concerned revision in short or
      long term. In both the total hip arthroplasty and knee arthroplasty populations,
      patients in the lowest income quintiles underwent revision surgery earlier than
      patients in the highest income groups, but this difference was not statistically
      significant. CONCLUSION: The quality of arthroplasty as measured by the risk of
      revision does not seem to depend on patients' income quintile.

PMID- 25376713
TI  - Hamstring tendon autograft versus LARS artificial ligament for arthroscopic
      posterior cruciate ligament reconstruction in a long-term follow-up.
AB  - INTRODUCTION: Surgical reconstruction has been increasingly recommended for the
      surgical management of posterior cruciate ligament (PCL) ruptures. While the
      choice of tissue graft still remains controversial. Currently both hamstring
      tendon autograft (HTG) and ligament advanced reinforcement system (LARS)
      artificial ligament are widely used but there are seldom reports on the
      comparisons of their clinical results. Our study was aimed to assess the
      effectiveness of these two grafts. MATERIALS AND METHODS: Thirty-five patients
      with unilateral PCL rupture were enrolled in this retrospectively study. Sixteen
      of them received arthroscopically assisted PCL reconstruction using hamstring
      tendon autografts (HTG group) and nineteen using LARS ligaments (LARS group). All
      cases were followed up for 46-57 months with a mean of 51 months. Follow-up
      examinations included radiographic assessment, Lysholm score, Tegner score,
      International Knee Documentation Committee (IKDC) rating scales and KT-1000 test.
      RESULTS: All patients improved significantly at the final follow-up compared with
      the examinational results preoperatively and there were no significant
      differences between HTG group and LARS group with respect to the results of
      radiographic assessment, Lysholm score, Tegner score, IKDC rating scales and KT
      1000 test. CONCLUSIONS: Similar good clinical results were obtained after PCL
      reconstruction using hamstring tendon autografts and LARS ligaments. Both LARS
      ligament and hamstring tendon autograft are ideal grafts for PCL reconstruction.

PMID- 25376714
TI  - Efficacy of the assisted self-reduction technique for acute anterior shoulder
      dislocation.
AB  - INTRODUCTION: The "original" traction-free Kocher's method to perform the
      reduction of shoulder dislocation has been recently reviewed and some authors
      speculated that it can be self performed by patients under the guide of the
      physician. In this way, as an "assisted self-reduction" technique, it is also
      effective and simple to perform. The aim is to study the effectiveness of the
      assisted self-reduction technique, in comparison to the well known and largely
      used traction-countertraction method. MATERIALS AND METHODS: From a consecutive
      series of 237 uncomplicated anterior shoulder dislocations, a total of 61 were
      managed by the residents of our institution under the supervision of the senior
      authors using the assisted self-reduction method and 176 were managed by other
      orthopaedic consultants on duty in the Emergency Department using the traction
      countertraction technique. Only the senior authors used the assisted self
      reduction technique, whereas the other orthopaedic consultants used the traction
      countertraction method. The need for intravenous sedation or general anaesthesia
      to perform the assisted self-reduction was considered a failure. Recorded
      variables were demographic data, previous dislocation, traumatic mechanism and
      medication use during shoulder reduction, time to perform the reduction. RESULTS:
      Ninety-eight percent of the acute dislocation treated with the assisted self
      reduction technique and 81 % treated with the traction-countertraction method
      were reducible without recourse to intravenous sedation. CONCLUSIONS: The
      assisted self-reduction technique is simple, effective and gentle. Physicians on
      duty in the Emergency Departments should therefore be encouraged to use it.

PMID- 25376715
TI  - SENSE and simultaneous multislice imaging.
AB  - PURPOSE: Simultaneous multislice (SMS) acquisitions play an important role in the
      challenge of increasing single-shot imaging speed. We show that sensitivity
      encoding in two spatial dimensions (two-dimensional sensitivity encoding [2D
      SENSE]) can be used to reconstruct SMS acquisitions with periodic but otherwise
      arbitrary undersampling patterns. THEORY AND METHODS: By adopting a 3D k-space
      representation of the SMS sampling process, the accelerated in-plane and slice
      encoding directions form a 2D-reconstruction problem that is equivalent to
      volumetric controlled aliasing in parallel imaging results in higher acceleration
      (CAIPIRINHA). 2D-SENSE does not otherwise distinguish between standard volumetric
      and SMS imaging with arbitrary CAIPIRINHA sampling. RESULTS: Use of the SENSE
      algorithm is demonstrated for in vivo brain data obtained with blipped-CAIPRINHA
      sampling in 2D SMS-echo planar imaging (EPI) and rapid acquisition with
      relaxation enhancement (RARE) acquisitions as well as 3D-EPI with various in
      plane and through-plane acceleration factors and CAIPIRINHA shifts. The proposed
      SENSE reconstruction works for any combination of SMS-factor and CAIPIRINHA shift
      by the addition of "dummy slices" that allow for noninteger undersampling in the
      slice direction. Images with commonly used slice-generalized autocalibrating
      partially parallel acquisitions reconstruction are shown for reference.
      CONCLUSION: SENSE is conceptually simple and provides a one-step reconstruction
      along both undersampled dimensions. It also provides a contrast-independent
      parallel imaging reconstruction for SMS.

PMID- 25376716
TI  - Reliability and validity of the Spanish version of the substance dependence
      severity scale.
AB  - PURPOSE: The purpose of this study was to estimate the reliability and provide
      evidence for the validity of the Spanish version of the Substance Dependence
      Severity Scale (SDSS). METHODS: A total of 211 substance abusers recruited at a
      public center that provides treatment for substance-related disorders in an
      outpatient setting were assessed. Reliability was estimated by Cronbach's alpha
      and test-retest. Validity evidence was studied by analyzing the relationships
      with the European Addiction Severity Index (EuropASI) and Health-Related Quality
      of Life for Drug Abusers (HRQoLDA). RESULTS: Adequate reliability coefficients
      were found for the dependence scales of all addressed substances (alpha = 0.737
      to 0.877; test-retest r = 0.796-0.952). Low internal consistency was found for
      the abuse scales (alpha = 0.329-0.694), and adequate test-retest coefficients on
      alcohol, cocaine and heroin (test-retest r = 0.708-0.902). The reliability of the
      cannabis abuse scales was inadequate. The SDSS scores showed significant
      relationships with the EuropASI and HRQoLDA dimensions. CONCLUSIONS: The
      psychometric analyses validate the use of the severity of dependence scales. The
      SDSS abuse scales must be used taking the limitations detected into
      consideration.

PMID- 25376717
TI  - Evaluating the effects of massed and distributed practice on acquisition and
      maintenance of tacts and textual behavior with typically developing children.
AB  - This study evaluated the effects of massed and distributed practice on the
      acquisition of tacts and textual behavior in typically developing children. We
      compared the effects of massed practice (i.e., consolidating all practice
      opportunities during the week into a single session) and distributed practice
      (i.e., distributing all practice opportunities across 4 sessions during the week)
      on the acquisition of textual behavior in English, tacting pictures of common
      nouns in Spanish, and textual behavior in Spanish using an adapted alternating
      treatments design embedded within a multiple probe design. We also examined
      correct responding during probes that (a) excluded prompts and reinforcement and
      (b) occurred 48 hr after training each week. The results indicated that
      distributed practice was the more efficient training format. Maintenance data
      collected up to 4 weeks after training also indicated that the participants
      consistently displayed higher levels of correct responding to targets that had
      been trained in distributed format. We discuss implications for practice and
      potential areas for future research.

PMID- 25376718
TI  - Qualitative and quantitative aspects of information processing in first
      psychosis: latent class analyses in patients, at-risk subjects, and controls.
AB  - We aimed to determine profiles of information processing deficits in the pathway
      to first psychosis. Sixty-one subjects at ultrahigh risk (UHR) for psychosis were
      assessed, of whom 18 converted to a first episode of psychosis (FEP) within the
      follow-up period. Additionally, 47 FEP and 30 control subjects were included.
      Using 10 neurophysiological parameters associated with information processing,
      latent class analyses yielded three classes at baseline. Class membership was
      related to group status. Within the UHR sample, two classes were found.
      Transition to psychosis was nominally associated with class membership.
      Neurophysiological profiles were unstable over time, but associations between
      specific neurophysiological components at baseline and follow-up were found. We
      conclude that certain constellations of neurophysiological variables aid in the
      differentiation between controls and patients in the prodrome and after first
      psychosis. 

PMID- 25376719
TI  - Effects of active hexose correlated compound on the seasonal variations of immune
      competence in healthy subjects.
AB  - The aim of this study was to evaluate the effects of active hexose correlated
      compound intake on the immune competence in healthy volunteers. Thirty-four
      subjects were randomized to receive placebo or active hexose correlated compound
      at 1.0 g/d for 4 weeks in early winter. Natural killer cell activity was
      significantly increased in both groups during the study period, the natural
      killer cell number, however, was not altered in the active hexose correlated
      compound group while placebo group showed remarkable decline. In addition, the
      score of immunological vigor, an index of total immune competence, was maintained
      in the active hexose correlated compound group although that of placebo group
      lowered during the test period. These results suggested that the continuous
      active hexose correlated compound intake maintained the immune competence against
      the seasonal change. 

PMID- 25376720
TI  - Notch signaling induces root resorption via RANKL and IL-6 from hPDL cells.
AB  - In this study, we first investigated the expressions of Jagged1, Notch2, the
      receptor activator of nuclear factor-kappa B ligand (RANKL), and interleukin (IL)
      6 in areas of root resorption during experimental tooth movement in rats in vivo.
      We then assessed the effects of compression force (CF) with or without GSI (an
      inhibitor of Notch signaling) on Jagged1, RANKL, and IL-6 release from human
      periodontal ligament (hPDL) cells. Twelve male 6-wk-old Wistar rats were
      subjected to an orthodontic force of 50 g to induce mesially tipping movement of
      the upper first molars for 7 d. The expression levels of tartrate-resistant acid
      phosphatase, Jagged1, Notch2, IL-6, and RANKL proteins in the dental root were
      determined using an immunohistochemical analysis. Furthermore, the effects of the
      CF on Jagged1, IL-6, and RANKL production were investigated using hPDL cells in
      vitro. The effects of the cell-conditioned medium obtained from the hPDL cells
      subjected to CF (CFM) and Jagged 1 on osteoclastogenesis of human osteoclast
      precursor cells (hOCPs) were also investigated. Under the conditions of
      experimental tooth movement in vivo, resorption lacunae with multinucleated cells
      were observed in the 50 g group. In addition, immunoreactivity for Jagged1,
      Notch2, IL-6, and RANKL was detected on day 7 in the PDL tissue subjected to the
      orthodontic force. In the in vitro study, the compression force increased the
      production of Jagged1, IL-6, and RANKL from the hPDL cells, whereas treatment
      with GSI inhibited the production of these factors in vitro. The
      osteoclastogenesis increased with the CFM and rhJagged1, and the increase in the
      osteoclastogenesis was almost inhibited by GSI. These results suggest that the
      Notch signaling response to excessive orthodontic forces stimulates the process
      of root resorption via RANKL and IL-6 production from hPDL cells. 

PMID- 25376721
TI  - Excess NF-kappaB induces ectopic odontogenesis in embryonic incisor epithelium.
AB  - Nuclear factor kappa B (NF-kappaB) signaling plays critical roles in many
      physiological and pathological processes, including regulating organogenesis.
      Down-regulation of NF-kappaB signaling during development results in hypohidrotic
      ectodermal dysplasia. The roles of NF-kappaB signaling in tooth development,
      however, are not fully understood. We examined mice overexpressing IKKbeta, an
      essential component of the NF-kappaB pathway, under keratin 5 promoter (K5
      Ikkbeta). K5-Ikkbeta mice showed supernumerary incisors whose formation was
      accompanied by up-regulation of canonical Wnt signaling. Apoptosis that is
      normally observed in wild-type incisor epithelium was reduced in K5-Ikkbeta mice.
      The supernumerary incisors in K5-Ikkbeta mice were found to phenocopy extra
      incisors in mice with mutations of Wnt inhibitor, Wise. Excess NF-kappaB activity
      thus induces an ectopic odontogenesis program that is usually suppressed under
      physiological conditions. 

PMID- 25376722
TI  - Contribution of donor and host mesenchyme to the transplanted tooth germs.
AB  - Autologous tooth germ transplantation of immature teeth is an alternative method
      of tooth replacement that could be used instead of dental implants in younger
      patients. However, it is paramount that the dental pulp remain vital and that
      root formation continue in the transplanted location. The goal of this study is
      to characterize the healing of allogenic tooth grafts in an animal model using
      GFP-labeled donor or host postnatal mice. In addition, the putative stem cells
      were labeled before transplantation with a pulse-chase paradigm. Transplanted
      molars formed cusps and roots and erupted into occlusion by 2 wk postoperatively.
      Host label-retaining cells (LRCs) were maintained in the center of pulp tissue
      associating with blood vessels. Dual labeling showed that a proportion of LRCs
      were incorporated into the odontoblast layer. Host cells, including putative
      dendritic cells and the endothelium, also immigrated into the pulp tissue but did
      not contribute to the odontoblast layer. Therefore, LRCs or putative mesenchymal
      stem cells are retained in the transplanted pulps. Hertwig's epithelial root
      sheath remains vital, and epithelial LRCs are present in the donor cervical
      loops. Thus, the dynamic donor-host interaction occurred in the developing
      transplant, suggesting that these changes affect the characteristics of the
      dental pulp. 

PMID- 25376723
TI  - Heterogeneous integration of epitaxial Ge on Si using AlAs/GaAs buffer
      architecture: suitability for low-power fin field-effect transistors.
AB  - Germanium-based materials and device architectures have recently appeared as
      exciting material systems for future low-power nanoscale transistors and photonic
      devices. Heterogeneous integration of germanium (Ge)-based materials on silicon
      (Si) using large bandgap buffer architectures could enable the monolithic
      integration of electronics and photonics. In this paper, we report on the
      heterogeneous integration of device-quality epitaxial Ge on Si using composite
      AlAs/GaAs large bandgap buffer, grown by molecular beam epitaxy that is suitable
      for fabricating low-power fin field-effect transistors required for continuing
      transistor miniaturization. The superior structural quality of the integrated Ge
      on Si using AlAs/GaAs was demonstrated using high-resolution x-ray diffraction
      analysis. High-resolution transmission electron microscopy confirmed relaxed Ge
      with high crystalline quality and a sharp Ge/AlAs heterointerface. X-ray
      photoelectron spectroscopy demonstrated a large valence band offset at the
      Ge/AlAs interface, as compared to Ge/GaAs heterostructure, which is a
      prerequisite for superior carrier confinement. The temperature-dependent
      electrical transport properties of the n-type Ge layer demonstrated a Hall
      mobility of 370 cm(2)/Vs at 290 K and 457 cm(2)/Vs at 90 K, which suggests
      epitaxial Ge grown on Si using an AlAs/GaAs buffer architecture would be a
      promising candidate for next-generation high-performance and energy-efficient fin
      field-effect transistor applications. 

PMID- 25376724
TI  - Patient satisfaction with health-care professionals and structure is not affected
      by longer hospital stay and complications after lung resection: a case-matched
      analysis.
AB  - OBJECTIVES: The objective of this investigation was to assess satisfaction with
      care of patients with long hospital stay (LHS) or complications after pulmonary
      resection in comparison with case-matched counterparts with a regular
      postoperative course. METHODS: This is a prospective observational analysis on
      171 consecutive patients submitted to pulmonary resections (78 wedges, 8
      segmentectomies, 83 lobectomies, 3 pneumonectomies) for benign (35), primary (93)
      or secondary malignant (43) diseases. A hospital stay >7 days was defined as long
      (LHS). Major cardiopulmonary complications were defined according to the ESTS
      database. Patient satisfaction was assessed by the administration of the EORTC IN
      PATSAT32 module at discharge. The questionnaire is a 32-item self-administered
      survey including different scales, reflecting the perceived level of satisfaction
      about the care provided by doctors, nurses and other personnel. To minimize
      selection bias, propensity score case-matching technique was applied to generate
      two sets of matched patients: patients with LHS with counterparts without it;
      patients with complications with counterparts without it. RESULTS: Median length
      of postoperative stay was 4 days (range 2-43). Forty-one patients (24%) had a
      hospital stay>7 days and 21 developed cardiopulmonary complications (12%).
      Propensity score yielded two well-matched groups of 41 patients with and without
      LHS. There were no significant differences in any patient satisfaction scale
      between the two groups. The comparison of the results of the patient satisfaction
      questionnaire between the two matched groups of 21 patients with and without
      complications did not show significant differences in any scale. CONCLUSIONS:
      Patients experiencing poor outcomes such as long hospital stay or complications
      have similar perception of quality of care compared with those with regular
      outcomes. Patient-reported outcome measures are becoming increasingly important
      in the evaluation of the quality of care and may complement more traditional
      objective indicators such as morbidity or length of stay.

PMID- 25376725
TI  - Asymptomatic anomalous origin of left anterior descending artery from the
      pulmonary artery and multiple atherosclerotic stenoses revealed by silent
      ischaemia.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery is a rare
      congenital disease responsible for a high mortality rate in childhood. Here, we
      report for the first time the case of an asymptomatic 61-year old patient showing
      a combination of anomalous origin of the left anterior descending artery from
      pulmonary artery and atherosclerotic stenosis in both the right coronary artery
      and the left circumflex artery without anomalous origin. 

PMID- 25376726
TI  - Patients with multiple nodules and a dominant lung adenocarcinoma have similar
      outcomes and survival compared with patients who have a solitary adenocarcinoma.
AB  - OBJECTIVES: Lepidic growth pattern lung adenocarcinoma commonly presents as a
      dominant lesion (DL) with associated pulmonary nodules either in the ipsilateral
      or contralateral lung fields, posing a challenge in clinical decision-making.
      These tumours may be clinically upstaged compared with those who present with
      solitary lesions and, as a result, may be offered different therapies. The
      purpose of this study is to compare recurrence rates, the development of new
      lesions and survival in patients with adenocarcinoma with a lepidic component
      presenting with a DL with or without additional nodules. METHODS: We performed a
      13-year retrospective chart review of patients with lepidic growth pattern
      adenocarcinoma. Patients were grouped into a uninodular group (UG) if they
      presented with a solitary lesion and a multinodular group (MG) if they had a DL
      with additional nodules. Clinicopathological features, outcomes and survival
      between the two groups were analysed. RESULTS: A total of 149 patients were
      identified: 62 (42%) in the UG and 87 (58%) in the MG. In addition to the DL, 217
      nodules were preoperatively identified in the MG: 60 were resected concomitantly
      with the DL, while 157 were radiologically surveyed. Invasive adenocarcinoma was
      the predominant pathological cell type in both groups. The median time of follow
      up was 3 years [interquartile range (IQR) 1.9-5.1]. Local (1 vs 2%), regional (1
      vs 3%) and distant recurrences (7 vs 4%) were detected, respectively, in the UG
      and the MG. In the UG, 20 new lesions were identified, while in the MG there were
      28. Only 4 of 157 (2.5%) surveyed pre-existing lesions were found to be malignant
      and required further treatment. No statistically significant differences were
      observed in 5-year disease-free and overall survival between the UG and the MG
      (82.3 vs 83.8%, P = 0.254 and 86.7 vs 93.8%, P = 0.096, respectively).
      CONCLUSIONS: We observed that patients with lepidic growth pattern adenocarcinoma
      presenting with a DL with associated secondary nodules appear to behave similarly
      to patients with a solitary lesion. Multiple nodules including those that are
      malignant in this specific subset of non-small-cell lung cancer should not be
      upstaged as advanced disease and patients should be treated with the same
      curative intent as those presenting with uninodular disease.

PMID- 25376727
TI  - Changes in sports injuries incidence over time in world-class road cyclists.
AB  - This is a descriptive epidemiologic survey on all traumatic and overuse injuries
      which occurred in 2 groups of male elite road cyclists based on retrospective
      clinical interviews and physical examinations. The historical group consisted of
      65 professional road cyclists surveyed from 1983 to 1995. The contemporary group
      included 65 elite racers still active and reporting injuries from 2003 to 2009.
      Injury/cyclist ratio was 1.32 in the historical group and 2.13 in those still
      active. Traumatic injuries increased from 39.5% (historical) to 53.9%
      (contemporary) (p<0.05). Severe traumatic lesions decreased from 49.9% in the
      historical group to 10.5% in the contemporary group (p<0.01). Patellofemoral pain
      decreased from 28.8% (historical) to 6.1% (contemporary) (p<0.01). Muscle
      injuries substantially increased from 13.4% to 44.9% (p<0.01). In the historical
      racers, the rates of risk for traumatic injury were 0.104 per year per cyclist,
      and 0.003 per 1 000 km of training and competition. These figures increased to
      0.287 and 0.009 respectively in the contemporary group. In summary, contemporary
      professional road cyclists are exposed to double the risk of traumatic injuries
      than those competing in the 80s and early 90s. However, these lesions have less
      severity. Overuse injuries had a completely different clinical pattern, with the
      currently active cyclist exhibiting more muscle injuries and less tendinous
      lesions. 

PMID- 25376728
TI  - Injuries in competitive boxing. A prospective study.
AB  - Boxing remains a subject of controversy and is often classified as dangerous. But
      the discussion is based mostly on retrospective studies. This survey was
      conducted as a prospective study. From October 2012 to September 2013, 44
      competitive boxers were asked to report their injuries once a month. The
      questionnaire collected general information (training, competition) and recorded
      the number of bouts fought, injuries and resulting lost days. A total of 192
      injuries were recorded, 133 of which resulted in interruption of training or
      competition. Each boxer sustained 3 injuries per year on average. The injury rate
      was 12.8 injuries per 1 000 h of training. Boxers fighting more than 3 bouts per
      year sustain more injuries (p=0.0075). The injury rate does is not a function of
      age (age<=19 vs. > 19a, p=0.53). Injuries to the head and the upper limbs occur
      most frequently. The most common injuries are soft tissue lacerations and
      contusions. Head injuries with neurological symptoms rarely occur (4.2%). Boxing
      has a high injury rate that is comparable with other contact sports, but most
      injuries are minor. Injury frequency is not a function of whether the boxer
      competes in the junior or adult category. Athletes fighting many bouts per year
      have a greater risk of injury. 

PMID- 25376729
TI  - Higher insulin-sensitizing response after sprint interval compared to continuous
      exercise.
AB  - This study investigated which exercise mode (continuous or sprint interval) is
      more effective for improving insulin sensitivity. Ten young, healthy men
      underwent a non-exercise trial (CON) and 3 exercise trials in a cross-over,
      randomized design that included 1 sprint interval exercise trial (SIE; 4 all-out
      30-s sprints) and 2 continuous exercise trials at 46% VO2peak (CELOW) and 77%
      VO2peak (CEHIGH). Insulin sensitivity was assessed using intravenous glucose
      tolerance test (IVGTT) 30 min, 24 h and 48 h post-exercise. Energy expenditure
      was measured during exercise. Glycogen in vastus lateralis was measured once in a
      resting condition (CON) and immediately post-exercise in all trials. Plasma
      lipids were measured before each IVGTT. Only after CEHIGH did muscle glycogen
      concentration fall below CON (P<0.01). All exercise treatments improved insulin
      sensitivity compared with CON, and this effect persisted for 48-h. However, 30
      min post-exercise, insulin sensitivity was higher in SIE than in CELOW and CEHIGH
      (11.5+/-4.6, 8.6+/-5.4, and 8.1+/-2.9 respectively; P<0.05). Insulin sensitivity
      did not correlate with energy expenditure, glycogen content, or plasma fatty
      acids concentration (P>0.05). After a single exercise bout, SIE acutely improves
      insulin sensitivity above continuous exercise. The higher post-exercise
      hyperinsulinemia and the inhibition of lipolysis could be behind the marked
      insulin sensitivity improvement after SIE. 

PMID- 25376730
TI  - The role of water intake on cardiac vagal reactivation after upper-body
      resistance exercise.
AB  - The aim of this study was to assess the hypothesis that water intake will
      accelerate cardiac vagal reactivation after a single session of upper-body
      resistance exercise. 13 healthy men (26.5+/-5.9 years) with previous experience
      in resistance training were enrolled. In visits 1 and 2, participants performed
      the one-repetition maximum (1RM) test and retest with the bench press exercise.
      The sessions 3 and 4 were performed randomly, while participants consumed 500 ml
      (experimental visit) or 50 ml (control visit) of water immediately after 3 sets
      of maximum repetitions at 80% of 1RM. Cardiac vagal activity was represented by
      cardiac vagal index (CVI) measured before, immediately after and 30 min post
      exercise. Additionally, heart rate and blood pressure were measured. The results
      show that CVI was higher 30 min post-exercise when 500 ml of water was ingested
      compared to 50 ml (1.39+/-0.07 vs. 1.23+/-0.07; p=0.02) (mean+/-SEM). Heart rate
      and blood pressure values were similar in both trials. We conclude that water
      intake accelerates post-resistance exercise cardiac vagal reactivation. These
      findings suggest that hydration after resistance exercise might be beneficial for
      cardiovascular safety in healthy subjects. 

PMID- 25376731
TI  - Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the
      transforming growth factor-beta pathway.
AB  - Dihydromyricetin (DHM) is a flavonoid compound which possesses potent antitumor
      activity. In the present study, it was demonstrated that DHM significantly
      inhibited proliferation and induced apoptosis in mouse hepatocellular carcinoma
      Hepal-6 cells. Transforming growth factor beta (TGF-beta) is recognized as a
      major profibrogenic cytokine and is therefore a common target for drugs in the
      treatment of liver disease. The present study aimed to investigate whether TGF
      beta was involved in DHM-triggered cell-viability inhibition and apoptosis
      induction. An MTT assay was used to evaluate the viability of Hepal-6 cells
      following DHM treatment. TGF-beta signalling is mediated by Smads and
      nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a crucial
      regulator of reactive oxygen species ROS production. TGF-beta, Smad3,
      phosphorylated (p)-Smad2/3 and NOX4 protein expression levels were evaluated by
      western blot analysis. TGF-beta and NOX4 gene expression levels were determined
      by quantitative polymerase chain reaction. The results indicated that DHM
      downregulated TGF-beta, Smad3, p-Smad2/3 and NOX4 in a concentration-dependent
      manner. A cell counting assay indicated that DHM also inhibited Hepal-6 cell
      growth in a concentration-dependent manner. TGF-beta expression was significantly
      decreased following DHM treatment. In conclusion, the results of the present
      study defined and supported a novel function for DHM, indicating that it induced
      cell apoptosis by downregulating ROS production via the TGF-beta/Smad3 signaling
      pathway in mouse hepatocellular carcinoma Hepal-6 cells.

PMID- 25376732
TI  - Is alcohol and community sport a good mix? Alcohol management, consumption and
      social capital in community sports clubs.
AB  - OBJECTIVE: Community sports clubs provide an important contribution to the health
      and wellbeing of individuals and the community; however, they have also been
      associated with risky alcohol consumption. This study assessed whether a club's
      alcohol management strategies were related to risky alcohol consumption by
      members and levels of social capital, as measured in terms of participation in
      and perceived safety of the club. METHOD: A total of 723 sports club members from
      33 community football clubs in New South Wales, Australia, completed a computer
      assisted telephone interview (CATI) and a management representative from each
      club also completed a CATI. The club representative reported on the club's
      implementation of 11 alcohol management practices, while club members reported
      their alcohol consumption and perceived levels of safety at the club and
      participation in the club. RESULTS: A structural equation model identified having
      the bar open for more than four hours; having alcohol promotions; and serving
      intoxicated patrons were associated with increased risky alcohol consumption
      while at the club; which in turn was associated with lower levels of perceived
      club safety and member participation. CONCLUSION AND IMPLICATIONS: The positive
      contribution of community sports clubs to the community may be diminished by
      specific inadequate alcohol management practices. Changing alcohol management
      practices can reduce alcohol consumption, and possibly increase perceived aspects
      of social capital, such as safety and participation.

PMID- 25376734
TI  - Origin of the unique ventilatory apparatus of turtles.
AB  - The turtle body plan differs markedly from that of other vertebrates and serves
      as a model system for studying structural and developmental evolution.
      Incorporation of the ribs into the turtle shell negates the costal movements that
      effect lung ventilation in other air-breathing amniotes. Instead, turtles have a
      unique abdominal-muscle-based ventilatory apparatus whose evolutionary origins
      have remained mysterious. Here we show through broadly comparative anatomical and
      histological analyses that an early member of the turtle stem lineage has several
      turtle-specific ventilation characters: rigid ribcage, inferred loss of
      intercostal muscles and osteological correlates of the primary expiratory muscle.
      Our results suggest that the ventilation mechanism of turtles evolved through a
      division of labour between the ribs and muscles of the trunk in which the
      abdominal muscles took on the primary ventilatory function, whereas the broadened
      ribs became the primary means of stabilizing the trunk. These changes occurred
      approximately 50 million years before the evolution of the fully ossified shell. 

PMID- 25376736
TI  - Exciton-Exciton Interaction and Optical Gain in Colloidal CdSe/CdS Dot/Rod
      Nanocrystals.
AB  - Exciton-exciton interaction in dot/rod CdSe/CdS nanocrystals has proved to be
      very sensitive to the shape of nanocrystals, due to the unique band alignment
      between CdSe and CdS. Repulsive exciton-exciton interaction is demonstrated,
      which makes CdSe/CdS dot/rods promising gain media for solution-processable
      lasers, with projected pump threshold densities below 1 kW cm(-2) for continuous
      wave lasing. 

PMID- 25376737
TI  - Diabetes empowerment and needs for self-management support among people with type
      2 diabetes in a rural inland community in northern Sweden.
AB  - BACKGROUND: Self-management among people with T2D includes being responsible for
      attaining a blood sugar level within the normal range, eating healthy food,
      exercising and following prescriptions for medication, something that may need
      support. In rural areas, access to health care may be limited, and support from
      family members becomes important. AIM: The aim of this study was to describe
      perceptions and associations of diabetes empowerment, self-management ability and
      needs of self-management support among people with T2D in a northern rural
      community of Sweden. METHOD: People with T2D (n = 159) living a rural
      municipality in northern Sweden answered the SWE-DES-23 questionnaire and
      additional questions concerning self-management and needs for self-management
      support. RESULTS: A higher diabetes empowerment was associated with longer
      diabetes duration and support from healthcare professionals and relatives. Women
      rated a need for self-management support significantly higher than men did.
      Nonretired persons rated a significantly higher need for self-management support
      and a lower perception of support from healthcare professionals compared to
      retired persons. Cohabitant persons had a significantly higher perception of
      support from relatives and also estimated a higher need for relatives'
      involvement in clinical visits compared to persons living alone. Both the newly
      diagnosed and also those people with a diabetes duration of 10-15 years rated a
      higher need for group support. Higher self-awareness and readiness to change were
      apparent among people with short and long diabetes duration. Furthermore, self
      management ability, support from healthcare professionals and from relatives and
      lastly diabetes duration was associated with diabetes empowerment. CONCLUSION:
      Not only people newly diagnosed with T2D should be offered patient-centred group
      support, strengthening patient empowerment. For future, family-focused care and
      education and training in person-centred care among diabetes specialist nurses is
      recommended.

PMID- 25376738
TI  - Biocompatible Polymers: Structurally Controlled Bio-hybrid Materials Based on
      Unidirectional Association of Anisotropic Microparticles with Human Endothelial
      Cells (Adv. Mater. 48/2009).
AB  - Biocompatible anisotropic polymer particles with bipolar affinity towards human
      endothelial cells are a novel type of building blocks for microstructured
      biohybrid materials, report Joerg Lahann and co-workers on p. 4920. Functional
      polarity due to two biologically distinct hemispheres has been achieved by
      synthesis of anisotropic particles via electro-hydrodynamic co-jetting of two
      different polymer solutions and subsequent selective surface modification. 

PMID- 25376735
TI  - VITamin D supplementation in renAL transplant recipients (VITALE): a prospective,
      multicentre, double-blind, randomized trial of vitamin D estimating the benefit
      and safety of vitamin D3 treatment at a dose of 100,000 UI compared with a dose
      of 12,000 UI in renal transplant recipients: study protocol for a double-blind,
      randomized, controlled trial.
AB  - BACKGROUND: In addition to their effects on bone health, high doses of
      cholecalciferol may have beneficial non-classic effects including the reduction
      of incidence of type 2 diabetes mellitus, cardiovascular disease, and cancer.
      These pleiotropic effects have been documented in observational and experimental
      studies or in small intervention trials. Vitamin D insufficiency is a frequent
      finding in renal transplant recipients (RTRs), and this population is at risk of
      the previously cited complications. METHODS/DESIGN: The VITALE study is a
      prospective, multicentre, double-blind, randomized, controlled trial with two
      parallel groups that will include a total of 640 RTRs. RTRs with vitamin D
      insufficiency, defined as circulating 25-hydroxyvitamin D levels of less than 30
      ng/ml (or 75 nmol/l), will be randomized between 12 and 48 months after
      transplantation to blinded groups to receive vitamin D3 (cholecalciferol) either
      at high or low dose (respectively, 100,000 UI or 12,000 UI every 2 weeks for 2
      months then monthly for 22 months) with a follow-up of 2 years. The primary
      objective of the study is to evaluate the benefit/risk ratio of high-dose versus
      low-dose cholecalciferol on a composite endpoint consisting of de novo diabetes
      mellitus; major cardiovascular events; de novo cancer; and patient death.
      Secondary endpoints will include blood pressure (BP) control; echocardiography
      findings; the incidences of infection and acute rejection episodes; renal
      allograft function using estimated glomerular filtration rate; proteinuria; graft
      survival; bone mineral density; the incidence of fractures; and biological
      relevant parameters of mineral metabolism. DISCUSSION: We previously reported
      that the intensive cholecalciferol treatment (100 000 IU every 2 weeks for 2
      months) was safe in RTR. Using a pharmacokinetic approach, we showed that
      cholecalciferol 100,000 IU monthly should maintain serum 25-hydroxyvitamin D at
      above 30 ng/ml but below 80 ng/ml after renal transplantation. Taken together,
      these results are reassuring regarding the safety of the cholecalciferol doses
      that will be used in the VITALE study. Analysis of data collected during the
      VITALE study will demonstrate whether high or low-dose cholecalciferol is
      beneficial in RTRs with vitamin D insufficiency. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01431430.

PMID- 25376739
TI  - Sodium hydrosulfide attenuates hyperhomocysteinemia rat myocardial injury through
      cardiac mitochondrial protection.
AB  - Hydrogen sulfide (H2S) plays an important role during rat myocardial injury.
      However, little is known about the role of H2S in hyperhomocysteinemia (HHcy)
      induced cardiac dysfunction as well as the underlying mechanisms. In this study,
      we investigated whether sodium hydrosulfide (NaHS, a H2S donor) influences
      methionine-induced HHcy rat myocardial injury in intact rat hearts and primary
      neonatal rat cardiomyocytes. HHcy rats were induced by methionine (2.0 g/kg) and
      the daily administration of 80 MUmol/L NaHS in the HHcy + NaHS treatment group.
      At the end of 4, 8, and 12 weeks, the ultrastructural alterations and functions
      of the hearts were observed using transmission electron microscopy and
      echocardiography system. The percentage of apoptotic cardiomyocytes, the
      mitochondrial membrane potential, and the production of reactive oxygen species
      (ROS) were measured. The expressions of cystathionine-gamma-lyase (CSE), Bax and
      Bcl-2, caspase-3, phospho-endothelial nitric oxide synthase and the mitochondrial
      NOX4 and cytochrome c were analyzed by Western blotting. The results showed the
      cardiac dysfunction, the ultrastructural changes, and the apoptotic rate increase
      in the HHcy rat hearts. In the primary neonatal rat cardiomyocytes of HHcy group,
      ROS production was increased markedly, whereas the expression of CSE was
      decreased. However, treatment with NaHS significantly improved the HHcy rat
      hearts function, the ultrastructural changes, and decreased the levels of ROS in
      the primary neonatal rat cardiomyocytes administrated with HHcy group.
      Furthermore, NaHS down-regulated the expression of mitochondrial NOX4 and caspase
      3 and Bax and inhibited the release of cytochrome c from mitochondria. In
      conclusion, H2S is involved in the attenuation of HHcy myocardial injury through
      the protection of cardiac mitochondria. 

PMID- 25376740
TI  - Metal-carbonyl units for vibrational and luminescence imaging: towards
      multimodality.
AB  - Metal-carbonyl complexes are attractive structures for bio-imaging. In addition
      to unique vibrational properties due to the CO moieties enabling IR and Raman
      cell imaging, the appropriate choice of ancillary ligands opens up the
      opportunity for luminescence detection. Through a classification by techniques,
      past and recent developments in the application of metal-carbonyl complexes for
      vibrational and luminescence bio-imaging are reviewed. Finally, their potential
      as bimodal IR and luminescent probes is addressed. 

PMID- 25376741
TI  - Clinical evaluation of two dental implant macrostructures on peri-implant bone
      loss: a comparative, retrospective study.
AB  - OBJECTIVES: To compare the effect of two implant macrostructures on peri-implant
      bone level. MATERIAL AND METHODS: This retrospective cohort study was conducted
      in a private practice. Patients received test (Nobel Speedy Groovy implants) or
      control implants (Mk III implants) or both. Baseline and corresponding follow-up
      radiographs, taken with a long-cone technique, were analyzed to evaluate mean
      bone level changes around implants during a mean follow-up of 69 +/- 19 months. A
      chi-squared test was performed to compare the bone level changes between the two
      types of implants. A multivariate analysis was used to explain the difference
      between the two groups. RESULTS: After controlling for inclusion and exclusion
      criteria, 144 dental implants corresponding to 68 implants in the test group and
      76 implants in the control group were placed in 59 patients. Nine dental implants
      (6.25%) were lost during the observation period: five implants in the test group
      and four implants in the control group. Consequently, a total of 135 implants
      placed in 58 patients were available for analysis. Our study shows a significant
      difference of peri-implant bone level overtime between the test and control
      groups (P < 0.01). At the end of the observation period, a bone growth was
      observed in the control group (0.02 +/- 0.80 mm), whereas a bone loss was found
      in the test group (-0.43 +/- 1.11 mm). The mean bone level at baseline and the
      type of periodontal therapy and the maintenance care program were involved in
      this difference (P < 0.001, P = 0.035, P < 0.001, respectively). CONCLUSION: Our
      study demonstrates a significant difference in peri-implant bone level between
      test and control groups. The mean bone level at baseline, the type of periodontal
      therapy, and the maintenance program may explain peri-implant bone level changes
      overtime.

PMID- 25376743
TI  - Association between rim enhancement of breast cancer on dynamic contrast-enhanced
      MRI and patient outcome: impact of subtype.
AB  - The heterogeneous nature of breast cancer is represented by three breast cancer
      subtypes associated with different patient outcome. However, within subtypes,
      variations still exist. Additional stratification is necessary for more
      individualized therapy. Functional tumor characteristics on dynamic contrast
      enhanced (DCE)-MRI may play a role. Rim enhancement of breast cancers has been
      associated with unfavorable pathology characteristics in the context of outcome.
      However, existence of a direct link is unknown. The purpose was to
      retrospectively determine the association between rim enhancement on DCE-MRI and
      long-term patient outcome, and whether it has complementary value to subtype.
      Preoperative DCE-MRI was performed in 556 consecutive female patients who were
      eligible for breast-conserving therapy. Presence of rim enhancement was assessed.
      Tumor characteristics were derived from resection specimens. Patients were
      stratified according to subtype. Association was assessed between rim enhancement
      and patient, pathology and treatment characteristics, recurrence-free interval
      and invasive disease-free survival. Median follow-up was 84 months. Patients were
      stratified into ER-positive/HER2-negative (N = 416), HER2-positive (N = 75), or
      triple-negative (N = 65) subtypes. Rim enhancement was seen in 29.0% (N =
      161/556) of tumors and was associated with higher histologic grade, negative ER
      status, and triple-negative subtype. Only within triple-negative tumors, an
      association was seen with outcome. Recurrence was lower in non-rim-enhancing
      tumors (N = 1/36; 2.8%) compared to rim-enhancing tumors (N = 9/28; 32.1%) (p =
      0.001). Survival was higher in non-rim-enhancing tumors (N = 34/36; 94.4%)
      compared to rim-enhancing tumors (N = 18/28; 64.3%) (p = 0.001). Rim enhancement
      on DCE-MRI is associated with long-term outcome of patients with triple-negative
      breast cancer and may potentially serve as a prognostic biomarker in these
      patients.

PMID- 25376744
TI  - Methylation of the BRCA1 promoter in peripheral blood DNA is associated with
      triple-negative and medullary breast cancer.
AB  - It has been proposed that methylation signatures in blood-derived DNA may
      correlate with cancer risk. In this study, we evaluated whether methylation of
      the promoter region of the BRCA1 gene detectable in DNA from peripheral blood
      cells is a risk factor for breast cancer, in particular for tumors with
      pathologic features characteristic for cancers with BRCA1 gene mutations. We
      conducted a case-control study of 66 breast cancer cases and 36 unaffected
      controls. Cases were triple-negative or of medullary histology, or both; 30
      carried a constitutional BRCA1 mutation and 36 did not carry a mutation. Blood
      for DNA methylation analysis was taken within three months of diagnosis.
      Methylation of the promoter of the BRCA1 gene was measured in cases and controls
      using methylation-sensitive high-resolution melting (MS-HRM). A sample with any
      detectable level of methylation was considered to be positive. Methylation of the
      BRCA1 promoter was detected in 15 of 66 cases and in 2 of 36 controls (OR 5.0, p
      = 0.03). Methylation was present in 15 of 36 women with breast cancer and without
      germline BRCA1 mutation, but in none of 30 women with breast cancer and a
      germline mutation (p < 0.01). The association between methylation and breast
      cancer was restricted to women with no constitutional BRCA1 mutation (OR 12.1, p
      = 0.0006). Methylation of the promoter of the BRCA1 gene detectable in peripheral
      blood DNA may be a marker of increased susceptibility to triple-negative or
      medullary breast cancer. 

PMID- 25376742
TI  - A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal
      Adhesion Kinase SH3/SH2-binding Region.
AB  - The c-Src tyrosine kinase co-operates with the focal adhesion kinase to regulate
      cell adhesion and motility. Focal adhesion kinase engages the regulatory SH3 and
      SH2 domains of c-Src, resulting in localized kinase activation that contributes
      to tumor cell metastasis. Using assay conditions where c-Src kinase activity
      required binding to a tyrosine phosphopeptide based on the focal adhesion kinase
      SH3-SH2 docking sequence, we screened a kinase-biased library for selective
      inhibitors of the Src/focal adhesion kinase peptide complex versus c-Src alone.
      This approach identified an aminopyrimidinyl carbamate compound, WH-4-124-2, with
      nanomolar inhibitory potency and fivefold selectivity for c-Src when bound to the
      phospho-focal adhesion kinase peptide. Molecular docking studies indicate that WH
      4-124-2 may preferentially inhibit the 'DFG-out' conformation of the kinase
      active site. These findings suggest that interaction of c-Src with focal adhesion
      kinase induces a unique kinase domain conformation amenable to selective
      inhibition. 

PMID- 25376745
TI  - What determines social capital in a social-ecological system? Insights from a
      network perspective.
AB  - Social capital is an important resource that can be mobilized for purposive
      action or competitive gain. The distribution of social capital in social
      ecological systems can determine who is more productive at extracting ecological
      resources and who emerges as influential in guiding their management, thereby
      empowering some while disempowering others. Despite its importance, the factors
      that contribute to variation in social capital among individuals have not been
      widely studied. We adopt a network perspective to examine what determines social
      capital among individuals in social-ecological systems. We begin by identifying
      network measures of social capital relevant for individuals in this context, and
      review existing evidence concerning their determinants. Using a complete social
      network dataset from Hawaii's longline fishery, we employ social network analysis
      and other statistical methods to empirically estimate these measures and
      determine the extent to which individual stakeholder attributes explain variation
      within them. We find that ethnicity is the strongest predictor of social capital.
      Measures of human capital (i.e., education, experience), years living in the
      community, and information-sharing attitudes are also important. Surprisingly, we
      find that when controlling for other factors, industry leaders and formal fishery
      representatives are generally not well connected. Our results offer new
      quantitative insights on the relationship between stakeholder diversity, social
      networks, and social capital in a coupled social-ecological system, which can aid
      in identifying barriers and opportunities for action to overcome resource
      management problems. Our results also have implications for achieving resource
      governance that is not only ecologically and economically sustainable, but also
      equitable. 

PMID- 25376747
TI  - Blepharoptosis Associated With Third Cranial Nerve Palsy.
AB  - PURPOSE: To evaluate the demographics and outcomes of management for
      blepharoptosis associated with third cranial nerve palsy at a tertiary eye
      center. METHODS: This retrospective cross-sectional and interventional study was
      performed on hospital records of patients with ptosis associated with third
      cranial nerve palsy who were referred to Labbafinejad Medical Center from January
      1999 to January 2009. The authors evaluated age, sex, laterality, severity of
      involvement, etiology, clinical findings, and treatment modalities and outcomes
      in patients with blepharoptosis due to third cranial nerve palsy over a 10-year
      period. RESULTS: Of a total of 45 subjects, 25 cases (55.6%) were males and 20
      subjects (44.4%) were females. Mean age of enrolled subjects was 21.1 +/- 15.5
      years. Etiologies included trauma in 21 (46.7%), congenital in 16 (35.6%), and
      other causes in 8 (17.7%) cases. Overall, 18 of 45 patients (40%) underwent
      ptosis surgery: of these, 15 (83.3%) subjects improved with one procedure,
      whereas 3 (16.7%) subjects required more than one operation. For initial ptosis
      surgery, 5 (27.7%) patients underwent levator resection and 13 (72.3%) cases
      underwent frontalis sling; all second and third procedures were frontalis sling.
      One-step, 2-step, and 3-step ptosis surgery was accomplished in 15 (83.3%), 1
      (5.6%), and 2 (11.1%) patients, respectively. Eventually, an open visual axis was
      attained in all cases following 1-3 operations. CONCLUSIONS: Trauma was the most
      common cause of ptosis associated with third cranial nerve palsy in the current
      series. Surgical management of ptosis in patients with third nerve palsy may be
      challenging but most subjects achieve good results following appropriate and
      stepwise surgical plans.

PMID- 25376746
TI  - Esophageal hypomotility and spastic motor disorders: current diagnosis and
      treatment.
AB  - Esophageal hypomotility (EH) is characterized by abnormal esophageal peristalsis,
      either from a reduction or absence of contractions, whereas spastic motor
      disorders (SMD) are characterized by an increase in the vigor and/or propagation
      velocity of esophageal body contractions. Their pathophysiology is not clearly
      known. The reduced excitation of the smooth muscle contraction mediated by
      cholinergic neurons and the impairment of inhibitory ganglion neuronal function
      mediated by nitric oxide are likely mechanisms of the peristaltic abnormalities
      seen in EH and SMD, respectively. Dysphagia and chest pain are the most frequent
      clinical manifestations for both of these dysfunctions, and gastroesophageal
      reflux disease (GERD) is commonly associated with these motor disorders. The
      introduction of high-resolution manometry (HRM) and esophageal pressure
      topography (EPT) has significantly enhanced the ability to diagnose EH and SMD.
      Novel EPT metrics in particular the development of the Chicago Classification of
      esophageal motor disorders has enabled improved characterization of these
      abnormalities. The first step in the management of EH and SMD is to treat GERD,
      especially when esophageal testing shows pathologic reflux. Smooth muscle
      relaxants (nitrates, calcium channel blockers, 5-phosphodiesterase inhibitors)
      and pain modulators may be useful in the management of dysphagia or pain in SMD.
      Endoscopic Botox injection and pneumatic dilation are the second-line therapies.
      Extended myotomy of the esophageal body or peroral endoscopic myotomy (POEM) may
      be considered in highly selected cases but lack evidence. 

PMID- 25376748
TI  - Counterion-assisted shaping of nanocluster supracrystals.
AB  - Ag44 (p-MBA)30 (4-) (p-MBA=para-mercaptobenzoic acid) nanocluster (NC)
      supracrystals (SCs) with customizable shapes can be obtained by simply altering
      the type and concentration of the counterions of the p-MBA ligands in the
      dimethylsulfoxide (DMSO)/water crystallization system. Changing the counterion of
      the p-MBA ligand from H(+) to Cs(+) eliminates the directional hydrogen bonds in
      the SCs, resulting in the packing of deprotonated Ag44 (p-MBA)30 (4-) NCs into
      octahedral SCs, which is in stark contrast to the rhombohedral SCs that were
      formed by the packing of protonated Ag44 (p-MBA)30 (4-) NCs in previous studies.
      Furthermore, the double layer of deprotonated Ag44 (p-MBA)30 (4-) NCs is
      sensitive to charge screening induced by increasing the Cs(+) concentration,
      thereby providing a means to regulate the precipitation kinetics of the Ag44 (p
      MBA)30 (4-) NCs for SC shape engineering. Slow precipitation kinetics was found
      to favor over-growth at the corners and edges of the octahedral SC nuclei,
      shaping the SCs into concave octahedra. 

PMID- 25376749
TI  - Regional and global antimicrobial susceptibility among isolates of Streptococcus
      pneumoniae and Haemophilus influenzae collected as part of the Tigecycline
      Evaluation and Surveillance Trial (T.E.S.T.) from 2009 to 2012 and comparison
      with previous years of T.E.S.T. (2004-2008).
AB  - BACKGROUND: We report here on 14438 Streptococcus pneumoniae and 14770
      Haemophilus influenzae isolates collected from 560 centres globally between 2004
      and 2012 as a part of the Tigecycline Evaluation and Surveillance Trial
      (T.E.S.T.). METHODS: MIC testing was performed using broth microdilution methods
      as described by the Clinical and Laboratory Standards Institute (CLSI) using CLSI
      approved breakpoints; US Food and Drug Administration breakpoints were used for
      tigecycline as CLSI breakpoints are not available. RESULTS: At least 99% of S.
      pneumoniae isolates globally were susceptible to levofloxacin, linezolid,
      tigecycline or vancomycin. Penicillin resistance was observed among 14.8% of S.
      pneumoniae and was highest in Asia/Pacific Rim (30.1%) and Africa (27.6%); 23.4%
      of S. pneumoniae isolates were penicillin-intermediate, which were most common in
      Africa (37.6%). Minocycline susceptibility among S. pneumoniae decreased by 20%
      between 2004-2008 and 2009-2012. High (>98.5%) susceptibility was reported among
      H. influenzae to all antimicrobial agents on the T.E.S.T. panel excluding
      ampicillin, to which only 78.3% were susceptible. beta-lactamase production was
      observed among 20.2% of H. influenzae isolates; 1.5% of isolates were beta
      lactamase negative, ampicillin-resistant. CONCLUSIONS: S. pneumoniae remained
      highly susceptible to levofloxacin, linezolid, tigecycline and vancomycin while
      H. influenzae was susceptible to most antimicrobial agents in the testing panel
      (excluding ampicillin).

PMID- 25376750
TI  - Robotic interface for transabdominal division of the levators and pelvic floor
      reconstruction in abdominoperineal resection: a case report and technical
      description.
AB  - BACKGROUND: Extralevator abdominoperineal resection (APR) in a prone jackknife
      position was developed to avoid a positive circumferential resection margin, and
      its application led to lower rates of local recurrence. The paper describes a
      technique of robotic extralevator APR with transabdominal levator division
      followed by pelvic floor reconstruction with bilayered composite mesh. METHODS: A
      42-year-old man with low rectal cancer required APR that was performed in a
      lithotomy position with transabdominal division of the levators. After the
      perineal phase, the robot was redocked and a bilayered composite mesh was sutured
      to the pelvic inlet using robotic needle drivers. RESULTS: The specimen had a
      cylindrical shape, and there was no surgical waist or perforation. Histology
      revealed a ypT2N0 tumor without circumferential margin involvement. CONCLUSIONS:
      The robotic interface can aid in APR by accurately transecting the levators from
      the top. Additionally, it allows suturing of mesh around the pelvic inlet to
      prevent perineal hernias. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25376751
TI  - Predictors of health care utilization in adult survivors of childhood cancer
      exposed to central nervous system-directed therapy.
AB  - BACKGROUND: Survivors of childhood cancer treated with central nervous system
      (CNS)-directed therapy may be at risk for poor health care utilization because of
      neurocognitive deficits. This study examined associations between neurocognitive
      function and adherence to routine and risk-based medical evaluations in adult
      survivors exposed to CNS-directed therapy. METHODS: Neurocognitive function and
      health care utilization were assessed in 1304 adult survivors of childhood cancer
      enrolled in the St. Jude Lifetime Cohort Study. Adherence to recommended care was
      defined as meeting guidelines published by the Children's Oncology Group.
      Multivariate models were used to evaluate associations between neurocognitive
      function and health screenings. Established predictors of health care utilization
      were included as covariates. Odds ratios (ORs) or prevalence ratios (PRs) and 95%
      confidence intervals (CIs) were calculated for variables maintained in the final
      models. RESULTS: Adherence to recommended medical care was higher for routine
      care (general physician care, 57.6%; dental care, 49.1%) versus specialized care
      (survivor-focused care, 21.9%; echocardiogram, 19.9%). Higher intelligence was
      predictive of general physician care (OR, 1.74; 95% CI, 1.41-2.15) and survivor
      focused care (OR, 1.44; 95% CI, 1.13-1.83) in comparison with no care, whereas
      better executive function skills were associated with reduced dental care (PR,
      0.94; 95% CI, 0.91-0.98). Echocardiogram monitoring was not associated with
      neurocognition. Possible late effects of cancer treatment (pain and reduced
      cardiorespiratory fitness) were associated with an increased likelihood of
      receiving specialized medical care. CONCLUSIONS: Survivors with reduced global
      cognition are at risk for poor health care utilization. Educational practices
      regarding recommended health care should be personalized to ensure comprehension
      by survivors with neurocognitive impairment.

PMID- 25376752
TI  - Alteration in regulatory T cells and programmed cell death 1-expressing
      regulatory T cells in active generalized vitiligo and their clinical correlation.
AB  - BACKGROUND: Vitiligo is an autoimmune depigmentation disease, and defects in
      regulatory T cells (Tregs) have been proposed in the pathogenesis of generalized
      vitiligo (GV). However, the role of programmed cell death (PD)1(+) Tregs has not
      been studied. OBJECTIVES: To investigate the status of Tregs, PD1(+) Tregs and
      associated parameters in active GV (aGV) during the first episode of disease
      attack and to establish the clinical correlation. METHODS: The percentages of
      circulating Tregs, PD1(+) Tregs and CD3(+) CD4(+) PD1(+) T cells were evaluated
      in 50 patients with aGV and 51 controls. Expression levels of FOXP3, TGFB1, CTLA4
      and genes for chemokine receptors (CCR4, CCR7) and their ligands (CCL21, CCL22)
      were quantified in peripheral blood and in lesional, perilesional, nonlesional
      and normal skin sections. The corresponding proteins were immunolocalized in
      tissue of aGV. RESULTS: The percentage of Tregs was decreased (P = 0.001) and
      that of PD1(+) Tregs increased (P = 0.001) in peripheral blood of patients with
      aGV compared with controls. The abundance of TGFB1 and CCL21 mRNA was
      significantly decreased in the peripheral blood of patients with aGV. Significant
      differences in forkhead box P3, transforming growth factor-beta and CCL21 protein
      expression were found in skin sections. CONCLUSIONS: Deficiency in Treg frequency
      and decreased expression of Treg-associated parameters (TGFB and CCL21) suggested
      a possible defect in Tregs that may alter their suppression function and skin
      homing in aGV. The increased PD1(+) Tregs suggests that the PD1/PD ligand pathway
      may be involved in aGV and may have a role in Treg exhaustion. Further study is
      required to delineate the effect of PD1 in regulating Treg function in aGV.

PMID- 25376753
TI  - Effects of mindfulness meditation on chronic pain: a randomized controlled trial.
AB  - OBJECTIVE: This randomized controlled clinical trial investigated the effects of
      mindfulness meditation on chronic pain. DESIGN: A total of 109 patients with
      nonspecific chronic pain were randomized to either a standardized mindfulness
      meditation program (mindfulness-based stress reduction [MBSR]) or to a wait list
      control. METHODS: Pain, physical function, mental function, pain acceptance, and
      health-related quality of life were measured. The SF36 vitality scale was chosen
      as the primary outcome measure; the primary end point was after completing the
      MBSR course. Within a 2.5-year period, 43 of the 109 randomized patients
      completed the mindfulness program, while 47 remained in the control group. Data
      were compared at three time points: at baseline, after completion of the
      course/waiting period, and at the 6-month follow-up. RESULTS: Significant effect
      (Cohen's d = 0.39) was found on the primary outcome measure, the SF36 vitality
      scale. On the secondary variables, significant medium to large size effects
      (Cohen's d = 0.37-0.71) were found for lower general anxiety and depression,
      better mental quality of life (psychological well-being), feeling in control of
      the pain, and higher pain acceptance. Small (nonsignificant) effect sizes were
      found for pain measures. There were no significant differences in the measures
      just after the intervention vs the 6-month follow-up. CONCLUSION: A standardized
      mindfulness program (MBSR) contributes positively to pain management and can
      exert clinically relevant effects on several important dimensions in patients
      with long-lasting chronic pain.

PMID- 25376755
TI  - Incidence rates of cranial tremors in essential tremor: a prospective,
      longitudinal study.
AB  - BACKGROUND: Cranial (head, jaw) tremors develop in a sizable number of essential
      tremor (ET) patients. They are particularly important because they are a
      significant source of embarrassment and are especially resistant to treatment.
      There are no data on the rate at which ET patients develop these cranial tremors.
      Our aim was to estimate the incidence rate of head and jaw tremors in ET.
      METHODS: Cases, enrolled in a prospective, longitudinal study, were evaluated at
      baseline and one follow-up visit. The in-person evaluation included
      questionnaires and a videotaped neurological examination, which was reviewed by a
      senior movement disorder neurologist for the presence/absence of head and jaw
      tremors. The mean time between baseline and follow-up assessments was 6.3 +/- 2.4
      (median = 6.0; range = 1.5-12.4 years). RESULTS: Five (6.3%) of 79 cases
      developed head tremor by follow-up (incidence rate = 1,012 per 100,000 person
      years; 95% confidence interval [CI] = 0-3,219). Twelve (10.6%) of 113 cases
      developed jaw tremor by follow-up (incidence rate = 1,692 per 100,000 person
      years; 95% CI = 0-1,692). CONCLUSION: These epidemiological data were designed to
      assist physicians in counseling ET patients when they ask about their risks of
      developing cranial tremors.

PMID- 25376756
TI  - Personality disorders, attachment and psychodynamic psychotherapy.
AB  - While attachment has been a fruitful and critical concept in understanding
      enduring individual templates for interpersonal relationships, it does not have a
      well-understood relationship to personality disorders, where impairment of
      interpersonal functioning is paramount. Despite the recognition that attachment
      disturbances do not simply reflect nonoptimal caretaking environments, the
      relationship of underlying temperamental factors to these environmental insults
      has not been fully explored. In this paper we provide an alternate model for the
      role of neurobiological temperamental factors, including brain circuitry and
      neuropeptide modulation, in mediating social cognition and the internalization
      and maintenance of attachment patterns. The implications of these altered
      attachment patterns on personality disorders and their neurobiological and
      environmental roots for psychoanalytically based treatment models designed to
      ameliorate difficulties in interpersonal functioning through the medium of
      increased access to mature forms of mentalization is discussed.

PMID- 25376758
TI  - Rapid transition from pemphigus vulgaris to pemphigus foliaceus.

PMID- 25376757
TI  - A model for time to fracture with a shock stream superimposed on progressive
      degradation: the Study of Osteoporotic Fractures.
AB  - Osteoporotic hip fractures in the elderly are associated with a high mortality in
      the first year following fracture and a high incidence of disability among
      survivors. We study first and second fractures of elderly women using data from
      the Study of Osteoporotic Fractures. We present a new conceptual framework,
      stochastic model, and statistical methodology for time to fracture. Our approach
      gives additional insights into the patterns for first and second fractures and
      the concomitant risk factors. Our modeling perspective involves a novel time-to
      event methodology called threshold regression, which is based on the plausible
      idea that many events occur when an underlying process describing the health or
      condition of a person or system encounters a critical boundary or threshold for
      the first time. In the parlance of stochastic processes, this time to event is a
      first hitting time of the threshold. The underlying process in our model is a
      composite of a chronic degradation process for skeletal health combined with a
      random stream of shocks from external traumas, which taken together trigger
      fracture events.

PMID- 25376759
TI  - Iron(II) complexes featuring kappa3- and kappa2-bound PNP pincer ligands--the
      significance of sterics.
AB  - Treatment of anhydrous FeX2 (X = Cl, Br) with 2 equiv. of the sterically little
      demanding N,N'-bisphosphino-2,6-diaminopyridine based PNP ligands--featuring Ph,
      biphenol (BIPOL), Me, Et, nPr, and nBu substituents at the phosphorus sites and
      H, Me, and Ph substituents at the N-linkers--afforded diamagnetic cationic
      octahedral complexes of the general formula [Fe(kappa(3)-P,N,P-PNP)(kappa(2)-P,N
      PNP)X](+) featuring a kappa(2)-P,N bound PNP ligand. With the sterically more
      encumbered N-methylated ligand PNP(Me)-Ph the related complex [Fe(kappa(3)-P,N,P
      PNP(Me)-Ph)(kappa(2)-P,N-PN(HMe)-Ph)Cl](+) rather than [Fe(kappa(3)-P,N,P-PNP(Me)
      Ph)Cl2] was formed. This reaction was accompanied by P-N bond cleavage, thereby
      forming the kappa(2)-P,N-bound N-diphenylphosphino-N,N'-methyl-2,6
      diaminopyridine ligand. In contrast, with the N-phenylated ligands PNP(Ph)-Et and
      PNP(Ph)-nPr, despite small Et and nPr substituents at the phosphorus sites,
      complexes [Fe(kappa(3)-P,N,P-PNP(Ph)-Et)Cl2] and [Fe(kappa(3)-P,N,P-PNP(Ph)
      nPr)Cl2] were formed, revealing that sterics can be also controlled by
      substituent variations at the amino N-sites. Depending on the solvent, complexes
      featuring kappa(2)-P,N-bound ligands undergo facile rearrangement reactions to
      give dicationic complexes of the type [Fe(kappa(3)-P,N,P-PNP)2](2+) where both
      PNP ligands are bound in a kappa(3)-P,N,P-fashion. In the presence of either
      Ag(+) or Na(+) salts as halide scavengers this reaction takes place within a few
      minutes. The pendant PR2 arm of the kappa(3)-kappa(2)-complexes is readily
      oxidized to the corresponding phosphine sulfides upon treatment with elemental
      sulfur. This was exemplarily shown for [Fe(kappa(3)-P,N,P-PNP-nPr)(kappa(2)-P,N
      PNS-nPr)Cl](+). Halide abstraction afforded the dicationic bis-chelated
      octahedral Fe(II) complex [Fe(kappa(3)-P,N,P-PNP)2](2+) together with the free
      SNP ligand rather than [Fe(kappa(3)-P,N,P-PNP-nPr)(kappa(3)-S,P,N-PNS-nPr)](2+).

PMID- 25376760
TI  - Expression of WT-1 by the vascular component of acral pseudolymphomatous
      angiokeratoma of children.
AB  - Acral pseudolymphomatous angiokeratoma of children (APACHE) is a disease
      comprised by a dense dermal infiltrate of B-lymphocytes and T-lymphocytes in
      which prominent blood vessels with plump endothelium are found. In the past, the
      lesion was interpreted as a variant of angiokeratoma, a vascular malformation, or
      a nevus. Currently, most authors consider it to be a type of pseudolymphoma with
      prominent blood vessels. The latter express CD34 and D2-40, while they lack the
      expression of Glut-1. The expression of Wilms tumor-1 (WT-1) by APACHE has not
      yet been studied. In this report, we present a case of APACHE on the right foot
      of a 4-year-old boy and demonstrate immunoexpression of WT-1 by the blood vessels
      of the lesion. We also performed serial sections and demonstrated that the WT-1+
      vessels with prominent endothelium were D2-40-. 

PMID- 25376761
TI  - AKI complications in critically ill patients: association with mortality rates
      and RRT.
AB  - BACKGROUND AND OBJECTIVES: AKI is associated with short- and long-term mortality.
      However, the exact contribution of AKI complications to the burden of mortality
      and whether RRT has any beneficial effect on reducing mortality rates in
      critically ill AKI patients are unknown. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This was a retrospective analysis using data from the
      Multiparameter Intelligent Monitoring in Intensive Care II project. A total of
      18,410 adult patients were enrolled from four intensive care units from a
      university hospital from 2001 to 2008. RESULTS: Overall, 10,245 patients
      developed AKI. After adjustments, the odds ratios (ORs) for hospital mortality
      were 1.73 (95% confidence interval [95% CI], 1.52 to 1.98) for AKI stage 1, 1.88
      (95% CI, 1.57 to 2.25) for stage 2, and 2.89 (95% CI, 2.41 to 3.46) for stage 3.
      Totals of 33%, 59%, and 70% of the excess mortality rates associated with AKI
      stages 1, 2, and 3, respectively, were attenuated by the inclusion of each AKI
      related complication in the model. The main burden of excess hospital mortality
      associated with AKI was attenuated by metabolic acidosis and cumulative fluid
      balance. Long-term mortality was not attenuated by any of the associated
      complications. Next, we used two different approaches to explore the associations
      between RRT, AKI complications, and hospital mortality: multivariate analysis and
      propensity score matching. In both approaches, the sensitivity analysis for RRT
      was associated with a better hospital survival in only the following AKI-related
      subgroups: hyperkalemia (OR, 0.55; 95% CI, 0.35 to 0.85), metabolic acidosis (OR,
      0.70; 95% CI, 0.53 to 0.92), cumulative fluid balance >5% of body weight (OR,
      0.60; 95% CI, 0.40 to 0.88), and azotemia (OR, 0.57; 95% CI, 0.40 to 0.81).
      CONCLUSIONS: A majority of the excess risk of mortality associated with AKI was
      attenuated by its fluid volume and metabolic complications, particularly in
      severe AKI. In addition, this study demonstrated that RRT is associated with a
      better outcome in patients with AKI-related complications.

PMID- 25376762
TI  - The medical director and quality requirements in the dialysis facility.
AB  - Four decades after the successful implementation of the ESRD program currently
      providing life-saving dialysis therapy to >430,000 patients, the definitions of
      and demands for a high-quality program have evolved and increased at the same
      time. Through substantial technological advances ESRD care improved, with a
      predominant focus on the technical aspects of care and the introduction of
      medications such as erythropoiesis-stimulating agents and active vitamin D for
      anemia and bone disease management. Despite many advances, the size of the
      program and the increasingly older and multimorbid patient population have
      contributed to continuing challenges for providing consistently high-quality
      care. Medicare's Final Rule of the Conditions for Coverage (April 2008) define
      the medical director of the dialysis center as the leader of the
      interdisciplinary team and the person ultimately accountable for quality, safety,
      and care provided in the center. Knowledge and active leadership with a hands-on
      approach in the quality assessment and performance improvement process (QAPI) is
      essential for the achievement of high-quality outcomes in dialysis centers. A
      collaborative approach between the dialysis provider and medical director is
      required to optimize outcomes and deliver evidence-based quality care. In 2011
      the Centers for Medicare & Medicaid Services introduced a pay-for-performance
      program-the ESRD quality incentive program (QIP)- with yearly varying quality
      metrics that result in payment reductions in subsequent years when targets are
      not achieved during the performance period. Success with the QIP requires a clear
      understanding of the structure, metrics, and scoring methods. Information on
      achievement and nonachievement is publicly available, both in facilities (through
      the facility performance score card) and on public websites (including Medicare's
      Dialysis Facility Compare). By assuming the leadership role in the quality
      program of dialysis facilities, the medical director is given an important
      opportunity to improve patients' lives and effect true change in a patient
      population dealing with a very challenging chronic disease. This article in the
      series on the role of the medical director summarizes the medical director's
      specific role in the quality improvement process in the dialysis facility and the
      associated requirements and programs, including QAPI and QIP.

PMID- 25376765
TI  - The National Institute of Diabetes and Digestive and Kidney Diseases Central
      Repositories: a valuable resource for nephrology research.
AB  - The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      Central Repositories, part of the National Institutes of Health (NIH), are an
      important resource available to researchers and the general public. The Central
      Repositories house samples, genetic data, phenotypic data, and study
      documentation from >100 NIDDK-funded clinical studies, in areas such as diabetes,
      digestive disease, and liver disease research. The Central Repositories also have
      an exceptionally rich collection of studies related to kidney disease, including
      the Modification of Diet in Renal Disease landmark study and recent data from the
      Chronic Renal Insufficiency Cohort and CKD in Children Cohort studies. The data
      are carefully curated and linked to the samples from the study. The NIDDK is
      working to make the materials and data accessible to researchers. The Data
      Repositories continue to improve flexible online searching tools that help
      researchers identify the samples or data of interest, and NIDDK has created
      several different paths to access the data and samples, including some funding
      initiatives. Over the past several years, the Central Repositories have seen
      steadily increasing interest and use of the stored materials. NIDDK plans to make
      more collections available and do more outreach and education about use of the
      datasets to the nephrology research community in the future to enhance the value
      of this resource. 

PMID- 25376764
TI  - Intradialytic hypotension and risk of cardiovascular disease.
AB  - BACKGROUND AND OBJECTIVES: Patients undergoing hemodialysis have an elevated risk
      of cardiovascular disease-related morbidity and mortality compared with the
      general population. Intradialytic hypotension (IDH) is estimated to occur during
      20%-30% of hemodialysis sessions. To date, no large studies have examined whether
      IDH is associated with cardiovascular outcomes. This study determined the
      prevalence of IDH according to interdialytic weight gain (IDWG) and studied the
      association between IDH and outcomes for cardiovascular events and mortality to
      better understand its role. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      study retrospectively examined records of 39,497 hemodialysis patients during
      2007 and 2008. US Renal Data System claims and dialysis provider data were used
      to determine outcomes. IDH was defined by current Kidney Disease Outcomes Quality
      Initiative guidelines (>=20 mmHg fall in systolic BP from predialysis to nadir
      intradialytic levels plus >=2 responsive measures [dialysis stopped, saline
      administered, etc.]). IDWG was measured absolutely (in kilograms) and relatively
      (in percentages). RESULTS: IDH occurred in 31.1% of patients during the 90-day
      exposure assessment period. At baseline, the higher the IDWG (relative or
      absolute), the greater the frequency of IDH (P<0.001). For all-cause mortality,
      the median follow-up was 398 days (interquartile range, 231-602 days). Compared
      with patients without IDH, IDH was associated with all-cause mortality (7646
      events; adjusted hazard ratio, 1.07 [95% confidence interval, 1.01 to 1.14]),
      myocardial infarction (2396 events; 1.20 [1.10 to 1.31]), hospitalization for
      heart failure/volume overload (8896 events; 1.13 [1.08 to 1.18]), composite
      hospitalization for heart failure/volume overload or cardiovascular mortality
      (10,805 events; 1.12 [1.08 to 1.17]), major adverse cardiac events (MACEs;
      myocardial infarction, stroke, cardiovascular mortality) (4994 events, 1.10 [1.03
      to 1.17]), and MACEs+ (MACEs plus arrhythmia or hospitalization for heart
      failure/volume overload) (12,221 events; 1.14 [1.09 to 1.19]). CONCLUSIONS: IDH
      was potently associated with cardiovascular morbidity and mortality. Clinical
      trials to ascertain causality are needed and should consider reduction in IDWG as
      a potential means to reduce IDH.

PMID- 25376766
TI  - Fluid management: the challenge of defining standards of care.

PMID- 25376767
TI  - Maintaining safety in the dialysis facility.
AB  - Errors in dialysis care can cause harm and death. While dialysis machines are
      rarely a major cause of morbidity, human factors at the machine interface and
      suboptimal communication among caregivers are common sources of error. Major
      causes of potentially reversible adverse outcomes include medication errors,
      infections, hyperkalemia, access-related errors, and patient falls. Root cause
      analysis of adverse events and "near misses" can illuminate care processes and
      show system changes to improve safety. Human factors engineering and simulation
      exercises have strong potential to define common clinical team purpose, and
      improve processes of care. Patient observations and their participation in error
      reduction increase the effectiveness of patient safety efforts. 

PMID- 25376763
TI  - AKI associated with cardiac surgery.
AB  - Approximately 18% of patients undergoing cardiac surgery experience AKI (on the
      basis of modern standardized definitions of AKI), and approximately 2%-6% will
      require hemodialysis. The development of AKI after cardiac surgery portends poor
      short- and long-term prognoses, with those developing RIFLE failure or AKI
      Network stage III having an almost 2-fold increase in the risk of death. AKI is
      caused by a variety of factors, including nephrotoxins, hypoxia, mechanical
      trauma, inflammation, cardiopulmonary bypass, and hemodynamic instability, and it
      may be affected by the clinician's choice of fluids and vasoactive agents as well
      as the transfusion strategy used. The risk of AKI may be ameliorated by avoidance
      of nephrotoxins, achievement of adequate glucose control preoperatively, and use
      of goal-directed therapy hemodynamic strategies. Remote ischemic preconditioning
      is an exciting future strategy, but more work is needed before widespread
      implementation. Unfortunately, there are no pharmacologic agents known to reduce
      the risk of AKI or treat established AKI. 

PMID- 25376769
TI  - Cancer registries in Japan: National Clinical Database and site-specific cancer
      registries.
AB  - The cancer registry is an essential part of any rational program of evidence
      based cancer control. The cancer control program is required to strategize in a
      systematic and impartial manner and efficiently utilize limited resources. In
      Japan, the National Clinical Database (NCD) was launched in 2010. It is a
      nationwide prospective registry linked to various types of board certification
      systems regarding surgery. The NCD is a nationally validated database using web
      based data collection software; it is risk adjusted and outcome based to improve
      the quality of surgical care. The NCD generalizes site-specific cancer registries
      by taking advantage of their excellent organizing ability. Some site-specific
      cancer registries, including pancreatic, breast, and liver cancer registries have
      already been combined with the NCD. Cooperation between the NCD and site-specific
      cancer registries can establish a valuable platform to develop a cancer care plan
      in Japan. Furthermore, the prognosis information of cancer patients arranged
      using population-based and hospital-based cancer registries can help in efficient
      data accumulation on the NCD. International collaboration between Japan and the
      USA has recently started and is expected to provide global benchmarking and to
      allow a valuable comparison of cancer treatment practices between countries using
      nationwide cancer registries in the future. Clinical research and evidence-based
      policy recommendation based on accurate data from the nationwide database may
      positively impact the public. 

PMID- 25376768
TI  - Complementary roles of the neuron-enriched endosomal proteins NEEP21 and calcyon
      in neuronal vesicle trafficking.
AB  - Understanding mechanisms governing the trafficking of transmembrane (TM) cargoes
      to synapses and other specialized membranes in neurons represents a long-standing
      challenge in cell biology. Investigation of the neuron-enriched endosomal protein
      of 21 kDa (NEEP21, or NSG1or P21) and Calcyon (Caly, or NSG3) indicates that the
      emergence of the NEEP21/Caly/P19 gene family could play a vital role in the
      success of these mechanisms in vertebrates. The upshot of a sizeable body of work
      is that the NEEP21 and Caly perform distinct endocytic and recycling functions,
      which impact (i) alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type
      glutamate receptor trafficking at excitatory synapses; (ii) transport to/in
      neuronal axons; as well as (iii) proteolytic processing of amyloid precursor
      protein and neuregulin 1, suggesting roles in neuron development, synaptic
      function, and neurodegeneration. We argue that their distinct effects on cargo
      endocytosis and recycling depend on interactions with vesicle trafficking and
      synaptic scaffolding proteins. As they play complementary, but opposing roles in
      cargo endocytosis, recycling, and degradation, balancing NEEP21 and Caly
      expression levels or activity could be important for homeostasis in a variety of
      signaling pathways, and also lead to a novel therapeutic strategy for disorders
      like Alzheimer's disease and schizophrenia. This review focuses on two closely
      related, neuron-enriched endosomal proteins: NEEP21 and Calcyon which perform
      distinct roles in regulating receptor endocytosis, recycling, and degradation.
      Based on an in-depth examination of the literature, we argue that these two
      proteins carry out complementary yet sometimes opposing vesicle trafficking
      functions that impact excitatory transmission, transcytosis, axonal transport,
      and also proteolytic processing by beta-secretase I (BACE1). Finally, we propose
      that balancing NEEP21 and Calcyon expression and/or activity could be important
      for homeostasis in a variety of signaling pathways, and also lead to a novel
      therapeutic strategy for disorders like Alzheimer's disease and schizophrenia.
      AMPA = alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; NMDA =
      N-Methyl-D-aspartate. 

PMID- 25376770
TI  - Long-term prognosis of patients with hepatitis B infection: causes of death and
      utility of nucleos(t)ide analogue therapy.
AB  - BACKGROUND: Long-term nucleos(t)ide analogue (NA) therapy for chronic hepatitis B
      (CHB) patients has been reported to reduce the risk of hepatocellular carcinoma
      (HCC) development. However, survival rates and causes of death in CHB patients
      either treated or not treated with NA therapy are unclear. Therefore, we
      investigated the prognosis of CHB in both of these groups. METHODS: A total of
      919 CHB patients who were treated (n = 189) or not treated (n = 730) with NA
      therapy were enrolled; of these, 135 were selected from each group by propensity
      score matching. Survival, mortality from both HCC and non-liver related diseases,
      and causes of death were analyzed. RESULTS: In all patients (n = 919), cumulative
      survival and mortality from both HCC and non-liver related diseases did not
      differ significantly according to NA therapy status. Of 66 patients who died
      during the follow-up period, 59.1% died due to liver-related diseases (including
      HCC); of the remainder, 48.1% died of non-liver related malignancies. In patients
      selected by propensity score matching (n = 270), cumulative survival and
      mortality from HCC were significantly improved in those who received NA therapy
      compared with those who did not (p = 0.015 and 0.018, respectively). Cox
      proportional hazards models indicated that NA therapy was independently
      associated with survival of CHB patients (hazard ratio, 0.286; 95% confidence
      interval, 0.122-0.668; p = 0.004). CONCLUSIONS: Approximately 40% of CHB patients
      died of non-liver-related diseases. Additionally, in patients who required anti
      viral therapy for CHB, NA therapy improved survival and mortality from HCC.

PMID- 25376771
TI  - On the pleotropic actions of mineralocorticoids.
AB  - Classical effects of mineralocorticoids include stimulation of Na(+) reabsorption
      and K(+) secretion in the kidney and other epithelia including colon and several
      glands. Moreover, mineralocorticoids enhance the excretion of Mg(2+) and renal
      tubular H(+) secretion. The renal salt retention following mineralocorticoid
      excess leads to extracellular volume expansion and hypertension. The increase of
      blood pressure following mineralocorticoid excess is, however, not only the
      result of volume expansion but may result from stiff endothelial cell syndrome
      impairing the release of vasodilating nitric oxide. Beyond that,
      mineralocorticoids are involved in the regulation of a wide variety of further
      functions, including cardiac fibrosis, platelet activation, neuronal function and
      survival, inflammation as well as vascular and tissue fibrosis and calcification.
      Those functions are briefly discussed in this short introduction to the special
      issue. Beyond that, further contributions of this special issue amplify on
      mineralocorticoid-induced sodium appetite and renal salt retention, the role of
      mineralocorticoids in the regulation of acid-base balance, the involvement of
      aldosterone and its receptors in major depression, the mineralocorticoid
      stimulation of inflammation and tissue fibrosis and the effect of aldosterone on
      osteoinductive signaling and vascular calcification. Clearly, still much is to be
      learned about the various ramifications of mineralocorticoid-sensitive physiology
      and pathophysiology.

PMID- 25376772
TI  - Free-running 4D whole-heart self-navigated golden angle MRI: Initial results.
AB  - PURPOSE: To test the hypothesis that both coronary anatomy and ventricular
      function can be assessed simultaneously using a single four-dimensional (4D)
      acquisition. METHODS: A free-running 4D whole-heart self-navigated acquisition
      incorporating a golden angle radial trajectory was implemented and tested in vivo
      in nine healthy adult human subjects. Coronary magnetic resonance angiography
      (MRA) datasets with retrospective selection of acquisition window width and
      position were extracted and quantitatively compared with baseline self-navigated
      electrocardiography (ECG) -triggered coronary MRA. From the 4D datasets, the left
      ventricular end-systolic, end-diastolic volumes (ESV & EDV) and ejection fraction
      (EF) were computed and compared with values obtained from conventional 2D cine
      images. RESULTS: The 4D datasets enabled dynamic assessment of the whole heart
      with isotropic spatial resolution of 1.15 mm(3). Coronary artery image quality
      was very similar to that of the ECG-triggered baseline scan despite some SNR
      penalty. A good agreement between 4D and 2D cine imaging was found for EDV, ESV,
      and EF. CONCLUSION: The hypothesis that both coronary anatomy and ventricular
      function can be assessed simultaneously in vivo has been tested positive.
      Retrospective and flexible acquisition window selection allows to best visualize
      each coronary segment at its individual time point of quiescence.

PMID- 25376774
TI  - The history of the cardiac emergency room, and the patient's history.

PMID- 25376773
TI  - Pocket-sized ultrasound examination of fluid imbalance in patients with heart
      failure: a pilot and feasibility study of heart failure nurses without prior
      experience of ultrasonography.
AB  - BACKGROUND: Detecting fluid imbalance in patients with chronic heart failure can
      be challenging. Use of a pocket-sized ultrasound device (PSUD) in addition to
      physical examination can be helpful to assess this important information. AIM: To
      evaluate the feasibility for nurses without prior experience of ultrasonography
      to examine fluid imbalance by the use of a PSUD on heart failure patients.
      METHOD: Four heart failure nurses and an expert cardiologist participated. The
      nurses underwent a four-hour PSUD training programme. One hundred and four heart
      failure outpatients were included. The examinations obtained information of
      pulmonary congestion, pleural effusion and the diameter of the vena cava
      inferior. RESULTS: Examinations took nine minutes on average. In 28% and 14% of
      the patients, pulmonary congestion and pleural effusion respectively were found
      by the nurses. The sensitivities and specificities for nurses' findings were 79%
      and 91%, and, 88% and 93% respectively. The inter-operator agreement between the
      nurses and the cardiologist reached a substantial level (kappa values: 0.71 and
      0.66). The inter-operator agreement for vena cava inferior reached a fair level
      (kappa value=0.39). Bland-Altman plots of the level of agreement revealed a mean
      difference of vena cava inferior diameter of 0.11 cm, while the 95% lower and
      upper limits ranged from -0.78 cm to 1.00 cm. CONCLUSION: After brief training,
      heart failure nurses can reliably identify pulmonary congestion and pleural
      effusion with a PSUD. Assessment of vena cava inferior was less valid. PSUD
      readings, when added to the history and a physical examination, can improve nurse
      assessment of fluid status in patients with heart failure.

PMID- 25376775
TI  - Parental decision making around perinatal autopsy: a qualitative investigation.
AB  - BACKGROUND: Decades of decline in uptake rates of perinatal autopsies has limited
      investigation into the causes and risk factors for stillbirth. AIMS: This study
      aimed to qualitatively explore perinatal autopsy decision-making processes in
      parents who experienced antepartum and intrapartum stillbirths. MATERIAL AND
      METHODS: A qualitative semi-structured interview format was utilized. The line of
      questioning centred on how parents came to decide on consenting or declining to
      have a perinatal autopsy undertaken. Interpretative phenomenological analysis was
      employed as the analytic strategy. Purposive sampling was used to recruit 10
      parents who either consented or declined autopsy from a large tertiary maternity
      hospital in Cork Ireland, where there were 30 stillbirths in 2011. RESULTS:
      Findings revealed four superordinate themes influencing parents' decision-making
      which varied with type of stillbirth experienced. Those parents who experienced
      antepartum stillbirths were more likely to consent; thus, knowing that the child
      was stillborn prior to delivery rather than on the day of delivery was associated
      with consent. In fact, these parents had more time for meaning-making; those
      consenting wanted to rule out self-blame and were fearful about future
      pregnancies. Parents who declined autopsy wanted to protect their infant from
      further harm. Interestingly, parents' knowledge and understanding of the autopsy
      itself were acquired primarily from public discourse. CONCLUSION: Parents'
      decision-making regarding autopsy is profoundly affected by their emotional
      response to stillbirth; clinicians and other health professionals may play a key
      role, especially if they can address parental concerns regarding the invasiveness
      of the autopsy procedure.

PMID- 25376776
TI  - The interplay of cyclic stretch and vascular endothelial growth factor in
      regulating the initial steps for angiogenesis.
AB  - Angiogenesis is regulated by chemical and mechanical factors in vivo. The
      regulatory role of mechanical factors and how chemical and mechanical angiogenic
      regulators work in concert remains to be explored. We investigated the effect of
      cyclic uniaxial stretch (20%, 1 Hz), with and without the stimulation of vascular
      endothelial growth factor (VEGF), on sprouting angiogenesis by employing a
      stretchable three-dimensional cell culture model. When compared to static
      controls, stretch alone significantly increased the density of endothelial
      sprouts, and these sprouts aligned perpendicular to the direction of stretch. The
      Rho-associated kinase (ROCK) inhibitor Y27632 suppressed stretch-induced
      sprouting angiogenesis and associated sprout alignment. While VEGF is a potent
      angiogenic stimulus through ROCK-dependent pathways, the combination of VEGF and
      stretch did not have an additive effect on angiogenesis. In the presence of VEGF
      stimulation, the ROCK inhibitor suppressed stretch-induced sprout alignment but
      did not affect stretch-induced sprout density; in contrast, the receptor tyrosine
      kinase (RTK) inhibitor sunitinib had no effect on stretch-induced alignment but
      trended toward suppressed stretch-induced sprout density. Our results suggest
      that the formation of sprouts and their directionality do not have completely
      identical regulatory pathways, and thus it is possible to separately manipulate
      the number and pattern of new sprouts.

PMID- 25376777
TI  - Screening of copy number variants in the 22q11.2 region of congenital heart
      disease patients from the Sao Miguel Island, Azores, revealed the second patient
      with a triplication.
AB  - BACKGROUND: The rearrangements in the 22q11.2 chromosomal region, responsible for
      the 22q11.2 deletion and microduplication syndromes, are frequently associated
      with congenital heart disease (CHD). The present work aimed to identify the
      genetic basis of CHD in 87 patients from the Sao Miguel Island, Azores, through
      the detection of copy number variants (CNVs) in the 22q11.2 region. These
      structural variants were searched using multiplex ligation-dependent probe
      amplification (MLPA). In patients with CNVs, we additionally performed
      fluorescent in situ hybridization (FISH) for the assessment of the exact number
      of 22q11.2 copies among each chromosome, and array comparative genomic
      hybridization (array-CGH) for the determination of the exact length of CNVs.
      RESULTS: We found that four patients (4.6%; A to D) carried CNVs. Patients A and
      D, both affected with a ventricular septal defect, carried a de novo 2.5 Mb
      deletion of the 22q11.2 region, which was probably originated by inter
      chromosomal (inter-chromatid) non-allelic homologous recombination (NAHR) events
      in the regions containing low-copy repeats (LCRs). Patient C, with an atrial
      septal defect, carried a de novo 2.5 Mb duplication of 22q11.2 region, which
      could have been probably generated during gametogenesis by NAHR or by unequal
      crossing-over; additionally, this patient presented a benign 288 Kb duplication,
      which included the TOP3B gene inherited from her healthy mother. Finally, patient
      B showed a 3 Mb triplication associated with dysmorphic facial features,
      cognitive deficit and heart defects, a clinical feature not reported in the only
      case described so far in the literature. The evaluation of patient B's parents
      revealed a 2.5 Mb duplication in her father, suggesting a paternal inheritance
      with an extra copy. CONCLUSIONS: This report allowed the identification of rare
      deletion and microduplication syndromes in Azorean CHD patients. Moreover, we
      report the second patient with a 22q11.2 triplication, and we suggest that
      patients with triplications of chromosome 22q11.2, although they share some
      characteristic features with the deletion and microduplication syndromes, present
      a more severe phenotype probably due to the major dosage of implicated genes.

PMID- 25376778
TI  - Mutations in the mitochondrial 12S rRNA gene in elderly Chinese people.
AB  - CONCLUSION: Our data indicate that the mitochondrial 12S rRNA gene, and
      particularly the A827G mutation, may be associated with susceptibility to age
      related hearing loss. OBJECTIVE: Hearing loss associated with aging is common
      among elderly persons. In all genetic backgrounds, mitochondrial DNA (mtDNA)
      mutations may be one of the most important factors contributing to aging and age
      related hearing loss. The mitochondrial 12S rRNA is a hot spot for deafness
      associated mutations in Chinese populations. The purpose of the present study was
      to elucidate the relationship of 12S rRNA gene polymorphisms and age-related
      hearing loss. METHODS: The 12S rRNA gene polymorphisms were detected by direct
      sequencing. Statistical analyses were performed to assess the associations
      between age-related hearing loss and 12S rRNA gene variants. RESULTS: We report
      here a systematic mutational screening of the mitochondrial 12S rRNA gene in 662
      elderly subjects from the general population with various hearing threshold
      levels (211 controls and 451 age-related hearing loss subjects). Mutational
      screening of the mitochondrial 12S rRNA gene identified 55 nucleotide changes,
      including 4 mutations localized at highly conserved sites and 51 known variants.
      Of the known deafness-associated mutations in the mitochondrial 12S rRNA gene,
      the incidence of the A1555G mutation was 0.15%, A827G was 4.38%, T1095C was
      0.45%, and T1005C was 3.78%. The incidence of the other known variants was 0.15
      99.85%. We found statistically significant differences in the proportions of
      subjects with the A827G mutation among the various age-related hearing loss
      groups and normal controls.

PMID- 25376779
TI  - Neurocognitive stages of spatial cognitive mapping measured during free
      exploration of a large-scale virtual environment.
AB  - Using a novel, fully mobile virtual reality paradigm, we investigated the EEG
      correlates of spatial representations formed during unsupervised exploration. On
      day 1, subjects implicitly learned the location of 39 objects by exploring a room
      and popping bubbles that hid the objects. On day 2, they again popped bubbles in
      the same environment. In most cases, the objects hidden underneath the bubbles
      were in the same place as on day 1. However, a varying third of them were
      misplaced in each block. Subjects indicated their certainty that the object was
      in the same location as the day before. Compared with bubble pops revealing
      correctly placed objects, bubble pops revealing misplaced objects evoked a
      decreased negativity starting at 145 ms, with scalp topography consistent with
      generation in medial parietal cortex. There was also an increased negativity
      starting at 515 ms to misplaced objects, with scalp topography consistent with
      generation in inferior temporal cortex. Additionally, misplaced objects elicited
      an increase in frontal midline theta power. These findings suggest that the
      successive neurocognitive stages of processing allocentric space may include an
      initial template matching, integration of the object within its spatial cognitive
      map, and memory recall, analogous to the processing negativity N400 and theta
      that support verbal cognitive maps in humans. 

PMID- 25376780
TI  - Whole-hand water flow stimulation increases motor cortical excitability: a study
      of transcranial magnetic stimulation and movement-related cortical potentials.
AB  - Previous studies examining the influence of afferent stimulation on corticospinal
      excitability have demonstrated that the intensity of afferent stimulation and the
      nature of the afferents targeted (cutaneous/proprioceptive) determine the
      effects. In this study, we assessed the effects of whole-hand water immersion
      (WI) and water flow stimulation (WF) on corticospinal excitability and
      intracortical circuits by measuring motor evoked potential (MEP) recruitment
      curves and conditioned MEP amplitudes. We further investigated whether whole-hand
      WF modulated movement-related cortical activity. Ten healthy subjects
      participated in three experiments, comprising the immersion of participants'
      right hands with (whole-hand WF) or without (whole-hand WI) water flow, and no
      immersion (control). We evaluated MEP recruitment curves produced by a single
      transcranial magnetic stimulation (TMS) pulse at increasing stimulus intensities,
      short-interval intracortical inhibition (SICI), and intracortical facilitation
      (ICF) using the paired TMS technique before and after 15 min of intervention.
      Movement-related cortical potentials (MRCPs) were evaluated to examine primary
      motor cortex, supplementary motor area, and somatosensory cortex excitability
      upon movement before and after whole-hand WF. After whole-hand WF, the slope of
      the MEP recruitment curve significantly increased, whereas SICI decreased and ICF
      increased in the contralateral motor cortex. The amplitude of the
      Bereitschaftspotential, negative slope, and motor potential of MRCPs
      significantly increased after whole-hand WF. We demonstrated that whole-hand WF
      increased corticospinal excitability, decreased SICI, and increased ICF, although
      whole-hand WI did not change corticospinal excitability and intracortical
      circuits. Whole-hand WF modulated movement-related cortical activity, increasing
      motor cortex activation for the planning and execution of voluntary movements. 

PMID- 25376781
TI  - Ghosts in the machine: memory interference from the previous trial.
AB  - Previous memoranda can interfere with the memorization or storage of new
      information, a concept known as proactive interference. Studies of proactive
      interference typically use categorical memoranda and match-to-sample tasks with
      categorical measures such as the proportion of correct to incorrect responses. In
      this study we instead train five macaques in a spatial memory task with
      continuous memoranda and responses, allowing us to more finely probe working
      memory circuits. We first ask whether the memoranda from the previous trial
      result in proactive interference in an oculomotor delayed response task. We then
      characterize the spatial and temporal profile of this interference and ask
      whether this profile can be predicted by an attractor network model of working
      memory. We find that memory in the current trial shows a bias toward the location
      of the memorandum of the previous trial. The magnitude of this bias increases
      with the duration of the memory period within which it is measured. Our
      simulations using standard attractor network models of working memory show that
      these models easily replicate the spatial profile of the bias. However, unlike
      the behavioral findings, these attractor models show an increase in bias with the
      duration of the previous rather than the current memory period. To model a bias
      that increases with current trial duration we posit two separate memory stores, a
      rapidly decaying visual store that resists proactive interference effects and a
      sustained memory store that is susceptible to proactive interference. 

PMID- 25376782
TI  - The complete frequency spectrum of physiological tremor can be recreated by
      broadband mechanical or electrical drive.
AB  - Two frequency peaks of variable preponderance have been reported for human
      physiological finger tremor. The high-frequency peak (20-25 Hz, seen only in
      postural tremor) is generally attributed to mechanical resonance, whereas the
      lower frequency peak (8-12 Hz, seen in both postural and kinetic tremor) is
      usually attributed to synchronous central or reflexive neural drive. In this
      study, we determine whether mechanical resonance could generate both peaks. In
      relaxed subjects, an artificial finger tremor was evoked by random mechanical
      perturbations of the middle finger or random electrical muscular stimulation of
      the finger extensor muscle. The high and the low frequencies observed in
      physiological tremor could both be created by either type of artificial input at
      appropriate input intensity. Resonance, inferred from cross-spectral gain and
      phase, occurred at both frequencies. To determine any neural contribution, we
      compared truly passive subjects with those who exhibited some electromyographic
      (EMG) activity in the finger extensor; artificially created tremor spectra were
      almost identical between groups. We also applied electrical stimuli to two
      clinically deafferented subjects lacking stretch reflexes. They exhibited the
      same artificial tremor spectrum as control subjects. These results suggest that
      both typical physiological finger tremor frequencies can be reproduced by random
      artificial input; neither requires synchronized neural input. We therefore
      suggest that mechanical resonance could generate both dominant frequency peaks
      characteristic of physiological finger tremor. The inverse relationship between
      the input intensity and the resulting tremor frequency can be explained by a
      movement-dependent reduction in muscle stiffness, a conjecture we support using a
      simple computational model. 

PMID- 25376784
TI  - Initiation and modulation of locomotor circuitry output with multisite
      transcutaneous electrical stimulation of the spinal cord in noninjured humans.
AB  - The mammalian lumbar spinal cord has the capability to generate locomotor
      activity in the absence of input from the brain. Previously, we reported that
      transcutaneous electrical stimulation of the spinal cord at vertebral level T11
      can activate the locomotor circuitry in noninjured subjects when their legs are
      placed in a gravity-neutral position (Gorodnichev RM, Pivovarova EA, Pukhov A,
      Moiseev SA, Savokhin AA, Moshonkina TR, Shcherbakova NA, Kilimnik VA, Selionov
      VA, Kozlovskaia IB, Edgerton VR, Gerasimenko IU. Fiziol Cheloveka 38: 46-56,
      2012). In the present study we hypothesized that stimulating multiple spinal
      sites and therefore unique combinations of networks converging on postural and
      locomotor lumbosacral networks would be more effective in inducing more robust
      locomotor behavior and more selective control than stimulation of more restricted
      networks. We demonstrate that simultaneous stimulation at the cervical, thoracic,
      and lumbar levels induced coordinated stepping movements with a greater range of
      motion at multiple joints in five of six noninjured subjects. We show that the
      addition of stimulation at L1 and/or at C5 to stimulation at T11 immediately
      resulted in enhancing the kinematics and interlimb coordination as well as the
      EMG patterns in proximal and distal leg muscles. Sequential cessation of
      stimulation at C5 and then at L1 resulted in a progressive degradation of the
      stepping pattern. The synergistic and interactive effects of transcutaneous
      stimulation suggest a multisegmental convergence of descending and ascending, and
      most likely propriospinal, influences on the spinal neuronal circuitries
      associated with locomotor activity. The potential impact of using multisite
      spinal cord stimulation as a strategy to neuromodulate the spinal circuitry has
      significant implications in furthering our understanding of the mechanisms
      controlling posture and locomotion and for regaining significant sensorimotor
      function even after a severe spinal cord injury. 

PMID- 25376783
TI  - Characteristics of GABAergic and cholinergic neurons in perinuclear zone of mouse
      supraoptic nucleus.
AB  - The perinuclear zone (PNZ) of the supraoptic nucleus (SON) contains some
      GABAergic and cholinergic neurons thought to innervate the SON proper. In mice
      expressing enhanced green fluorescent protein (eGFP) in association with
      glutamate decarboxylase (GAD)65 we found an abundance of GAD65-eGFP neurons in
      the PNZ, whereas in mice expressing GAD67-eGFP, there were few labeled PNZ
      neurons. In mice expressing choline acetyltransferase (ChAT)-eGFP, large,
      brightly fluorescent and small, dimly fluorescent ChAT-eGFP neurons were present
      in the PNZ. The small ChAT-eGFP and GAD65-eGFP neurons exhibited a low-threshold
      depolarizing potential consistent with a low-threshold spike, with little
      transient outward rectification. Large ChAT-eGFP neurons exhibited strong
      transient outward rectification and a large hyperpolarizing spike afterpotential,
      very similar to that of magnocellular vasopressin and oxytocin neurons. Thus the
      large soma and transient outward rectification of large ChAT-eGFP neurons suggest
      that these neurons would be difficult to distinguish from magnocellular SON
      neurons in dissociated preparations by these criteria. Large, but not small, ChAT
      eGFP neurons were immunostained with ChAT antibody (AB144p). Reconstructed
      neurons revealed a few processes encroaching near and passing through the SON
      from all types but no clear evidence of a terminal axon arbor. Large ChAT-eGFP
      neurons were usually oriented vertically and had four or five dendrites with
      multiple branches and an axon with many collaterals and local arborizations.
      Small ChAT-eGFP neurons had a more restricted dendritic tree compared with
      parvocellular GAD65 neurons, the latter of which had long thin processes oriented
      mediolaterally. Thus many of the characteristics found previously in
      unidentified, small PNZ neurons are also found in identified GABAergic neurons
      and in a population of smaller ChAT-eGFP neurons. 

PMID- 25376785
TI  - Anodal transcranial direct current stimulation applied over the supplementary
      motor area delays spontaneous antiphase-to-in-phase transitions.
AB  - Coordinated bimanual oscillatory movements often involve one of two intrinsically
      stable phasing relationships characterized as in-phase (symmetrical) or antiphase
      (asymmetrical). The in-phase mode is typically more stable than antiphase, and if
      movement frequency is increasing during antiphase movements, a spontaneous
      transition to the in-phase pattern occurs. There is converging neurophysiological
      evidence that the supplementary motor area (SMA) plays a critical role in the
      successful performance of these patterns, especially during antiphase movements.
      We investigated whether modulating the excitability of the SMA via offline
      transcranial direct current stimulation (tDCS) would delay the onset of anti-to
      in-phase transitions. Participants completed two sessions (separated by ~48 h),
      each consisting of a pre- and post-tDCS block in which they performed metronome
      paced trials of rhythmic in- and antiphase bimanual supination-pronation
      movements as target oscillation frequency was systematically increased. Anodal or
      cathodal tDCS was applied over the SMA between the pre- and post-tDCS blocks in
      each session. Following anodal tDCS, participants performed the antiphase pattern
      with increased accuracy and stability and were able to maintain the coordination
      pattern at a higher oscillation frequency. Antiphase performance was unchanged
      following cathodal tDCS, and neither tDCS polarity affected the in-phase mode.
      Our findings suggest increased SMA excitability induced by anodal tDCS can
      improve antiphase performance and adds to the accumulating evidence of the
      pivotal role of the SMA in interlimb coordination. 

PMID- 25376786
TI  - Intrinsic excitability varies by sex in prepubertal striatal medium spiny
      neurons.
AB  - Sex differences in neuron electrophysiological properties were traditionally
      associated with brain regions directly involved in reproduction in adult,
      postpubertal animals. There is growing acknowledgement that sex differences can
      exist in other developmental periods and brain regions as well. This includes the
      dorsal striatum (caudate/putamen), which shows robust sex differences in gene
      expression, neuromodulator action (including dopamine and 17beta-estradiol), and
      relevant sensorimotor behaviors and pathologies such as the responsiveness to
      drugs of abuse. Here we examine whether these sex differences extend to striatal
      neuron electrophysiology. We test the hypothesis that passive and active medium
      spiny neuron (MSN) electrophysiological properties in prepubertal rat dorsal
      striatum differ by sex. We made whole cell recordings from male and females MSNs
      from acute brain slices. The slope of the evoked firing rate to current injection
      curve was increased in MSNs recorded from females compared with males. The
      initial action potential firing rate was increased in MSNs recorded from females
      compared with males. Action potential after-hyperpolarization peak was decreased,
      and threshold was hyperpolarized in MSNs recorded from females compared with
      males. No sex differences in passive electrophysiological properties or miniature
      excitatory synaptic currents were detected. These findings indicate that MSN
      excitability is increased in prepubertal females compared with males, providing a
      new mechanism that potentially contributes to generating sex differences in
      striatal-mediated processes. Broadly, these findings demonstrate that sex
      differences in neuron electrophysiological properties can exist prepuberty in
      brain regions not directly related to reproduction. 

PMID- 25376788
TI  - Isn't functional neuroimaging all about Ca2+ signaling in astrocytes?
AB  - Extensive research over the past decades about the multifaceted roles of brain
      astrocytes led to the suggestion that the signals observed with functional
      neuroimaging might primarily reflect astrocytic rather than neuronal activity.
      The basis for this paradigm-shifting concept was the evidence for an involvement
      of astrocytes in the control of local cerebral blood flow through intracellular
      Ca(2+) signaling. In this Neuro Forum, I discuss new important experimental
      findings obtained by Jego et al. (Jego P, Pacheco-Torres J, Araque A, Canals S. J
      Cereb Blood Flow Metab 34: 1599-1603, 2014) as well as other closely related
      studies published recently, prompting a dismissal of substantial astrocytic
      contribution in functional neuroimaging. 

PMID- 25376787
TI  - Enriching the diet with menhaden oil improves peripheral neuropathy in
      streptozotocin-induced type 1 diabetic rats.
AB  - The purpose of this study was to determine the effect of supplementing the diet
      of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is
      a natural source for n-3 fatty acids, which have been shown to have beneficial
      effects in cardiovascular disease and other morbidities. Streptozotocin-induced
      diabetic rats were used to examine the influence of supplementing their diet with
      25% menhaden oil on diabetic neuropathy. Both prevention and intervention
      protocols were used. Endpoints included motor and sensory nerve conduction
      velocity, thermal and mechanical sensitivity, and innervation and sensitivity of
      the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints
      was found to be progressive. Menhaden oil did not improve elevated HbA1C levels
      or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic
      and had reduced motor and sensory nerve conduction velocities, and innervation
      and sensitivity of the cornea and skin were impaired. These endpoints were
      significantly improved with menhaden oil treatment following the prevention or
      intervention protocol. We found that supplementing the diet of type 1 diabetic
      rats with menhaden oil improved a variety of endpoints associated with diabetic
      neuropathy. These results suggest that enriching the diet with n-3 fatty acids
      may be a good treatment strategy for diabetic neuropathy. 

PMID- 25376789
TI  - Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal
      calcium sensor protein-1: relevance to schizophrenia and bipolar disorder.
AB  - Reduced levels of gamma-band activity are present in schizophrenia and bipolar
      disorder patients. In the same disorders, increased neuronal calcium sensor
      protein-1 (NCS-1) expression was reported in a series of postmortem studies.
      These disorders are also characterized by sleep dysregulation, suggesting a role
      for the reticular activating system (RAS). The discovery of gamma-band activity
      in the pedunculopontine nucleus (PPN), the cholinergic arm of the RAS, revealed
      that such activity was mediated by high-threshold calcium channels that are
      regulated by NCS-1. We hypothesized that NCS-1 normally regulates gamma-band
      oscillations through these calcium channels and that excessive levels of NCS-1,
      such as would be expected with overexpression, decrease gamma-band activity. We
      found that PPN neurons in rat brain slices manifested gamma-band oscillations
      that were increased by low levels of NCS-1 but suppressed by high levels of NCS
      1. Our results suggest that NCS-1 overexpression may be responsible for the
      decrease in gamma-band activity present in at least some schizophrenia and
      bipolar disorder patients. 

PMID- 25376790
TI  - Multicenter phase II study of apatinib in non-triple-negative metastatic breast
      cancer.
AB  - BACKGROUND: Apatinib is a tyrosine kinase inhibitor targeting vascular
      endothelial growth factor receptor 2(VEGFR-2). This study was conducted to assess
      the efficacy and safety of apatinib in patients with non-triple-negative
      metastatic breast cancer who had received prior chemotherapy for their metastatic
      disease. METHODS: This multicenter, open-label, single arm study enrolled
      patients with non-triple-negative breast cancer, pretreated with anthracycline,
      taxanes and capecitabine, and who failed in the metastatic setting at least 1 and
      at most 4 prior chemotherapy regimens and at least one endocrine drug for hormone
      receptor-positive patients as well as at least one anti-Her2 drug for Her2
      positive patients. The primary end point of this study was progression free
      survival (PFS). Secondary end points included objective response rate (ORR),
      disease control rate (DCR), overall survival (OS), and toxicity. Apatinib was
      administered as 500 mg daily on days 1 through 28 of each 4-week cycle. RESULTS:
      38 patients were enrolled with a median age of 49 years (range, 35 to 62 years)
      and received apatinib for a median of 4 cycles (range from 0 to 10 cycles). 18
      (47.4%) patients experienced dose reduction during treatment. The median relative
      dose intensity (relative to assigned dose for each cycle) was 82% (range, 45.0%
      to 100.0%). Median follow-up time was 10.1 months. Median PFS of all 38 patients
      was 4.0 months (95% confidence interval (CI), 2.8 m - 5.2 m). 36 patients were
      eligible for efficacy analysis. ORR was 16.7% (6/36). DCR was 66.7% (24/36).
      Median OS was 10.3 months (95% CI, 9.1 m - 11.6 m). The most common grade 3/4
      treatment-related AEs were hypertension (20.5%), hand-foot syndrome (10.3%), and
      proteinuria (5.1%). Of three possibly drug-related SAEs recorded in the study, 2
      (3.4%) deaths occurred within 28 days of last treatment and were both considered
      to be the result of disease progression. The other one was grade 2 diarrhea
      needing hospitalization. CONCLUSIONS: Apatinib exhibited objective efficacy in
      heavily pretreated, metastatic non-triple-negative breast cancer with manageable
      toxicity, and it might be better to be tested in breast cancer with high
      angiogenesis dependency. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01653561.

PMID- 25376791
TI  - The helix-loop-helix protein id1 controls stem cell proliferation during
      regenerative neurogenesis in the adult zebrafish telencephalon.
AB  - The teleost brain has the remarkable ability to generate new neurons and to
      repair injuries during adult life stages. Maintaining life-long neurogenesis
      requires careful management of neural stem cell pools. In a genome-wide
      expression screen for transcription regulators, the id1 gene, encoding a negative
      regulator of E-proteins, was found to be upregulated in response to injury. id1
      expression was mapped to quiescent type I neural stem cells in the adult
      telencephalic stem cell niche. Gain and loss of id1 function in vivo demonstrated
      that Id1 promotes stem cell quiescence. The increased id1 expression observed in
      neural stem cells in response to injury appeared independent of inflammatory
      signals, suggesting multiple antagonistic pathways in the regulation of reactive
      neurogenesis. Together, we propose that Id1 acts to maintain the neural stem cell
      pool by counteracting neurogenesis-promoting signals.

PMID- 25376792
TI  - Referrals to a specialised dizziness clinic often result in revised diagnoses and
      new therapeutic advice.
AB  - BACKGROUND: Patients with dizziness are frequently referred to specialised
      centres for a second opinion. The incremental diagnostic and therapeutic yield of
      this approach has rarely been studied. AIM OF THE STUDY: How often is a new
      diagnosis or treatment advice given to patients with dizziness who are referred
      for a second opinion to a tertiary multi-disciplinary expertise centre? METHODS:
      In a prospective observational study, the following data were collected: reason
      for referral, diagnosis and treatment made by ENT surgeon and a neurologist in
      consensus. RESULTS: In the complete group of patients (n = 327), a new (or
      amended) diagnosis was made in 54% and 62% of the patients received a new
      treatment advice. CONCLUSION: Referral of selected dizzy patients to a
      multidisciplinary centre provides a revised diagnosis or treatment recommendation
      for a majority of patients.

PMID- 25376793
TI  - Renal function is the same 6 months after robot-assisted partial nephrectomy
      regardless of clamp technique: analysis of outcomes for off-clamp, selective
      arterial clamp and main artery clamp techniques, with a minimum follow-up of 1
      year.
AB  - OBJECTIVE: To compare the renal functional outcomes, with >1 year of follow-up,
      of patients who underwent robot-assisted partial nephrectomy (RAPN) performed
      with different clamping techniques. PATIENTS AND METHODS: The peri-operative data
      of patients undergoing RAPN performed with different clamping techniques were
      retrospectively analysed (group 1: off-clamp, n = 23; group 2: selective clamp, n
      = 25; group 3: main artery clamp, n = 114). The main outcome measures were
      postoperative serum creatinine level, estimated glomerular filtration rate (eGFR)
      and percentage change in eGFR, the data for which were collected at periodic
      intervals during the first 12 months and annually thereafter, in addition to late
      eGFR value. Only patients with >1 year of follow-up were included in the
      analysis. RESULTS: The baseline characteristics of groups 2 and 3 were similar,
      while patients in group 1 had smaller sized tumours and lower tumour complexity.
      The median follow-up periods were 45 (group 1), 20 (group 2) and 47 (group 3)
      months. The median clamping times were 24.8 min in the main artery clamp and 18
      min in the selective artery clamp groups. Group 2 had greater median blood loss
      volume (100 vs 500 vs 200 mL for groups 1, 2 and 3, respectively; P < 0.01) and a
      longer length of hospital stay (3 vs 4 vs 3 days for groups 1, 2 and 3,
      respectively; P = 0.02). No significant differences were found among the groups
      with regard to transfusion rates, positive surgical margin rates, complications,
      recurrence or mortality rates. Groups 1 and 2 had significantly less
      deterioration of postoperative renal function during the first 3 months after
      surgery (P = 0.04; percent change in eGFR -1.5, -2 and -8% for groups 1, 2 and 3,
      respectively), but this beneficial outcome was not observed after 6 months or for
      the latest eGFR measurement (P = 0.48; latest percent change in eGFR -3, -6 and 
      3.5% for groups 1, 2 and 3, respectively). In regression analysis, baseline eGFR,
      type of clamp procedure and tumour complexity score were predictive of normal
      renal function 7 days after surgery, while only baseline eGFR and age could
      predict it 1 year postoperatively. CONCLUSIONS: Off-clamp and selective artery
      clamp techniques result in superior short-term renal functional outcomes compared
      with the main artery clamp approach; however, after the 6th postoperative month,
      there were no significant differences regarding the functional outcome among the
      above surgical techniques, as long as the warm ischaemia time was 20-30 min.

PMID- 25376794
TI  - Overexpression of MIC-3 indicates a direct role for the MIC gene family in
      mediating Upland cotton (Gossypium hirsutum) resistance to root-knot nematode
      (Meloidogyne incognita).
AB  - KEY MESSAGE: Transgene-based analysis of the MIC-3 gene provides the first report
      of a cotton gene having a direct role in mediating cotton resistance to root-knot
      nematode. Major quantitative trait loci have been mapped to Upland cotton
      (Gossypium hirsutum L.) chromosomes 11 and 14 that govern the highly resistant
      phenotype in response to infection by root-knot nematode (RKN; Meloidogyne
      incognita); however, nearly nothing is known regarding the underlying molecular
      determinants of this RKN-resistant phenotype. Multiple lines of circumstantial
      evidence have strongly suggested that the MIC (Meloidogyne Induced Cotton) gene
      family plays an integral role in mediating cotton resistance to RKN. In this
      report, we demonstrate that overexpression of MIC-3 in the RKN-susceptible
      genetic background Coker 312 reduces RKN egg production by ca. 60-75 % compared
      to non-transgenic controls and transgene-null sibling lines. MIC-3 transcript and
      protein overexpression were confirmed in root tissues of multiple independent
      transgenic lines with each line showing a similar level of increased resistance
      to RKN. In contrast to RKN fecundity, transgenic lines showed RKN-induced root
      galling similar to the susceptible controls. In addition, we determined that this
      effect of MIC-3 overexpression was specific to RKN as no effect was observed on
      reniform nematode (Rotylenchulus reniformis) reproduction. Transgenic lines did
      not show obvious alterations in growth, morphology, flowering, or fiber quality
      traits. Gene expression analyses showed that MIC-3 transcript levels in
      uninfected transgenic roots exceeded levels observed in RKN-infected roots of
      naturally resistant plants and that overexpression did not alter the regulation
      of native MIC genes in the genome. These results are the first report describing
      a direct role for a specific gene family in mediating cotton resistance to a
      plant-parasitic nematode.

PMID- 25376795
TI  - Femoral head and neck excision in cats: medium- to long-term functional outcome
      in 18 cats.
AB  - OBJECTIVE: To assess the medium- to long-term functional outcome of cats after
      femoral head and neck excision (FHNE) using an owner-completed questionnaire.
      METHODS: Cats that had FHNE and were free of other orthopaedic or medical
      conditions that could affect their mobility, other than the studied coxofemoral
      joint(s), were included. A specific owner-completed questionnaire was used at a
      minimum of 4 months postoperatively. The questionnaire assessed the ability of
      the cats to perform normal feline activities, change of demeanour or behaviour,
      the necessity for long-term analgesia and the time taken to resume normal
      activities. RESULTS: Eighteen cats had undergone uni- or bilateral FHNE and met
      the inclusion criteria. All but one cat could perform normal feline activities
      without or with slight difficulty at follow-up. The aforementioned cat had
      notable, persistent difficulty in climbing. The majority of the cats took between
      1 and 2 months to resume normal activity. No change in demeanour or behaviour was
      noted in any of the cats and none of the cats required long-term analgesia.
      CONCLUSIONS AND RELEVANCE: Based on the owner-completed questionnaire, cats have
      good-to-excellent medium- to long-term functional outcome after adequately
      performed FHNE.

PMID- 25376796
TI  - Abdominal ultrasonographic findings in acromegalic cats.
AB  - OBJECTIVES: Acromegaly is increasingly recognized as a cause of insulin
      resistance in cats with diabetes mellitus (DM). The objective of this study was
      to determine if ultrasonographic changes in selected abdominal organs of
      acromegalic cats could be used to raise the index of suspicion for this
      condition. METHODS: In this retrospective case-control study, medical records of
      cats presenting to North Carolina State University or Colorado State University
      from January 2002 to October 2012 were reviewed. Cats were included in the
      acromegaly group if they had insulin-resistant DM with increased serum insulin
      like growth factor (IGF-1) concentrations and had an abdominal ultrasound
      examination performed with report available. A control group included age-matched
      cats that had abdominal ultrasound examination performed for investigation of
      disease unlikely to involve the kidneys, adrenal glands, pancreas or liver.
      RESULTS: Twenty-four cats were included in each group. IGF-1 concentrations in
      the acromegaly group ranged from >148 to 638 nmol/l. When compared with age
      matched controls, cats with acromegaly demonstrated significantly increased
      median left and right kidney length, significantly increased median left and
      right adrenal gland thickness, and significantly increased median pancreatic
      thickness. Hepatomegaly and bilateral adrenomegaly were reported in 63% and 53%
      of acromegalic cats, respectively, and in none of the controls. Pancreatic
      abnormalities were described in 88% of the acromegalic cats and 8% of the
      controls. CONCLUSIONS AND RELEVANCE: These findings indicate that compared with
      non-acromegalic cats, age-matched acromegalic patients have measurably larger
      kidneys, adrenal glands and pancreas. Diagnostic testing for acromegaly should be
      considered in poorly regulated diabetic cats exhibiting organomegaly on abdominal
      ultrasound examination.

PMID- 25376797
TI  - Application of micro-computed tomography to microstructure studies of the
      medicinal fungus Hericium coralloides.
AB  - The potential of 3-D nondestructive imaging techniques such as micro-computed
      tomography (micro-CT) was evaluated to study morphological patterns of the
      potential medicinal fungus Hericium coralloides (Basidiomycota). Micro-CT results
      were correlated with histological information gained from scanning electron
      microscopy (SEM) and light microscopy (LM). It is demonstrated that the
      combination of these imaging methods results in a more distinct picture of the
      morphology of the edible and potentially medicinal Hericium coralloides
      basidiomata. In addition we have created 3-D reconstructions and visualizations
      based on micro-CT imagery from a randomly selected part of the upper region of a
      fresh H. coralloides basidioma: Analyses for the first time allowed an
      approximation of the evolutionary effectiveness of this bizarrely formed
      basidioma type in terms of the investment of tissue biomass and its reproductive
      output (production of basidiospores). 

PMID- 25376798
TI  - Taxonomy and phylogeny of yellow Clavaria species with clamped basidia-Clavaria
      flavostellifera sp. nov. and the typification of C. argillacea, C. flavipes and
      C. sphagnicola.
AB  - This study explores species limits of a group of Clavaria species with taxonomic
      and nomenclatural problems and discusses the phylogeny and circumscription of the
      genus. The nuc 28S rDNA (28S) and internal transcribed spacer region phylogenies
      resolve species relationships, and the ITS is shown to be an adequate barcode
      marker for Clavaria. Yellow, clamped species of Clavaria are distributed in two
      clades, (i) C. flavostellifera, sister to C. incarnata and C. asterospora in ITS
      analyses, characterized by producing ornamented spores, and (ii) C. argillacea-C.
      citrinorubra-C. flavipes-C. sphagnicola, with smooth spores. Clavaria
      flavostellifera is described as new species based on morphological and molecular
      characters. Molecular evidence that supports C. sphagnicola as distinct from C.
      argillacea is provided. The usefulness of spore ornamentation as a taxonomic
      character is discussed; it is present only in some taxa and then only on spores
      trapped in the hymenium. Descriptions of C. argillacea, C. flavipes and C.
      sphagnicola are provided, along with color photographs and a key to yellow
      species of Clavaria with clamped basidia. Camarophyllopsis and Clavicorona are
      recovered within a paraphyletic Clavaria in our 28S phylogeny. Clampless
      contextual hyphae and narrow, slightly thick-walled mycelial hyphae are proposed
      as synapomorphies of Camarophyllopsis and Clavaria. 

PMID- 25376799
TI  - Unexpectedly low UV-sensitivity in a bird, the budgerigar.
AB  - Photoreceptor adaptation ensures appropriate visual responses during changing
      light conditions and contributes to colour constancy. We used behavioural tests
      to compare UV-sensitivity of budgerigars after adaptation to UV-rich and UV-poor
      backgrounds. In the latter case, we found lower UV-sensitivity than expected,
      which could be the result of photon-shot noise corrupting cone signal robustness
      or nonlinear background adaptation. We suggest that nonlinear adaptation may be
      necessary for allowing cones to discriminate UV-rich signals, such as bird
      plumage colours, against UV-poor natural backgrounds. 

PMID- 25376800
TI  - Extensive population decline in the Tasmanian devil predates European settlement
      and devil facial tumour disease.
AB  - The Tasmanian devil (Sarcophilus harrisii) was widespread in Australia during the
      Late Pleistocene but is now endemic to the island of Tasmania. Low genetic
      diversity combined with the spread of devil facial tumour disease have raised
      concerns for the species' long-term survival. Here, we investigate the origin of
      low genetic diversity by inferring the species' demographic history using
      temporal sampling with summary statistics, full-likelihood and approximate
      Bayesian computation methods. Our results show extensive population declines
      across Tasmania correlating with environmental changes around the last glacial
      maximum and following unstable climate related to increased 'El Nino-Southern
      Oscillation' activity. 

PMID- 25376801
TI  - Managing anabolic steroids in pre-hibernating Arctic ground squirrels: obtaining
      their benefits and avoiding their costs.
AB  - Androgens have benefits, such as promoting muscle growth, but also significant
      costs, including suppression of immune function. In many species, these trade
      offs in androgen action are reflected in regulated androgen production, which is
      typically highest only in reproductive males. However, all non-reproductive
      Arctic ground squirrels, irrespective of age and sex, have high levels of
      androgens prior to hibernating at sub-zero temperatures. Androgens appear to be
      required to make muscle in summer, which, together with lipid, is then
      catabolized during overwinter. By contrast, most hibernating mammals catabolize
      only lipid. We tested the hypothesis that androgen action is selectively enhanced
      in Arctic ground squirrel muscle because of an upregulation of androgen receptors
      (ARs). Using Western blot analysis, we found that Arctic ground squirrels have AR
      in skeletal muscle more than four times that of Columbian ground squirrels, a
      related southern species that overwinters at approximately 0 degrees C and has
      low pre-hibernation androgen levels. By contrast, AR in lymph nodes was
      equivalent in both species. Brain AR was also modestly but significantly
      increased in Arctic ground squirrel relative to Columbian ground squirrel. These
      results are consistent with the hypothesis that tissue-specific AR regulation
      prior to hibernation provides a mechanism whereby Arctic ground squirrels obtain
      the life-history benefits and mitigate the costs associated with high androgen
      production. 

PMID- 25376802
TI  - Infected honeybee foragers incur a higher loss in efficiency than in the rate of
      energetic gain.
AB  - Parasites, by altering the nutritional and energetic state of their hosts, can
      significantly alter their foraging behaviour. In honeybees, an infection with
      Nosema ceranae has been shown to lower the energetic state of individual bees,
      bringing about changes in behaviours associated with foraging. Comparing the
      foraging trip times, hive times in between trips, and the crop contents of
      uninfected and infected foragers as they depart on foraging trips and return from
      them, this study examined how any differences in these variables influence
      alternative foraging currencies. The results show that infected bees take longer
      foraging trips, spend shorter time in the hive between successive trips and bring
      back less sugar from each trip. These changes have a stronger adverse effect on
      their efficiency of energetic gain as compared with their rate of energetic gain,
      which has important implications for individual and colony life history. 

PMID- 25376804
TI  - Are empidine dance flies major flower visitors in alpine environments? A case
      study in the Alps, France.
AB  - Pollination is one of the most important ecosystem services and bees the most
      important pollinators. As a population decline of bees has been documented in
      numerous regions of the world, it is crucial to develop understanding on other
      possible pollinators. Here, we study the potential pollination impact of Diptera,
      and among them Empidinae, in an alpine environment, where the abundance of bees
      is naturally lower. Interactions between 19 entomophilous plants and their flower
      visitors were recorded in a subalpine meadow in the French Alps during six weeks.
      Visitation frequencies were used to build the flower-visitor network. Our results
      show that interactions between flies and plants are dominant; flies represent
      more than 60% of all visitors, with 54% of them being Empidinae. We especially
      found that flies, Empidinae and bees are the main visitors of 11, three and one
      plants, respectively. When considering both bees and Syrphidae together, six
      plants were more visited by Empidinae; when considering bees and Syrphidae
      separately, 10 plants were more visited by Empidinae than by bees or Syrphidae.
      The results support the idea that flies widely replace bees as main flower
      visitors at altitude, and among them the Empidinae might play a key role in
      pollination. 

PMID- 25376803
TI  - Dynamic visual cues induce jaw opening and closing by tiger beetles during
      pursuit of prey.
AB  - In dynamic locomotory contexts, visual cues often trigger adaptive behaviour by
      the viewer, yet studies investigating how animals determine impending collisions
      typically employ either stationary viewers or objects. Here, we describe a
      dynamic situation of visually guided prey pursuit in which both impending prey
      contact and escape elicit observable adaptive behaviours in the pursuer, a
      predatory beetle. We investigated which visual cues may independently control
      opening and closing of the beetle's jaws during chases of prey dummies. Jaw
      opening and closing typically occur when prey is within the 60 degrees  binocular
      field, but not at specific distances, angular sizes or time-to-collision. We show
      that a sign change in the expansion rate of the target image precedes jaw opening
      (16 ms) and closing (35 ms), signalling to the beetle that it is gaining on the
      target or that the target is getting away. We discuss the 'sloppiness' of such
      variation in the lag of the behavioural response, especially jaw closing, as an
      adaptation to uncertainty about target position due to degradation of the target
      image by motion blur from the fast-running beetle. 

PMID- 25376805
TI  - Recent divergences and size decreases of eastern gorilla populations.
AB  - Compared with other African apes, eastern gorillas (Gorilla beringei) have been
      little studied genetically. We used analysis of autosomal DNA genotypes obtained
      from non-invasively collected faecal samples to estimate the evolutionary
      histories of the two extant mountain gorilla populations and the closely related
      eastern lowland gorillas. Our results suggest that eastern lowland gorillas and
      mountain gorillas split beginning some 10 000 years ago, followed 5000 years ago
      by the split of the two mountain gorilla populations of Bwindi Impenetrable
      National Park and the Virungas Massif. All three populations have decreased in
      effective population size, with particularly substantial 10-fold decreases for
      the mountain gorillas. These dynamics probably reflect responses to habitat
      changes resulting from climate fluctuations over the past 20 000 years as well as
      increasing human influence in this densely populated region in the last several
      thousand years. 

PMID- 25376806
TI  - Silk flow-diverter stent for the treatment of intracranial aneurysms: a series of
      58 patients with emphasis on long-term results.
AB  - BACKGROUND AND PURPOSE: The Silk flow-diverter stent is increasingly used to
      treat complex intracranial aneurysms including wide-neck, fusiform aneurysms.
      Sparse data are available concerning long-term results of this technique. We
      report our 5-year experience with Silk stent treatment of intracranial aneurysms.
      MATERIALS AND METHODS: A retrospective review of our prospectively maintained
      database identified all patients treated by the Silk stent in 2 institutions.
      Clinical charts, procedural data, and angiographic results were reviewed.
      RESULTS: Between July 2009 and May 2014, we identified 58 patients with 70
      intracranial aneurysms. Endovascular treatment was successful in 93% of patients
      with 32 treated with the first-generation Silk stent and 26 with the new Silk+
      stent. Mean follow-up in 47 patients was 22 months. Despite an 11% delayed
      complication rate, overall permanent neurologic morbidity was 5.5%. All
      complications were seen with the first-generation Silk stent. There was no
      procedure-related mortality. Long-term anatomic results showed 73% with complete
      occlusion, 16% with neck remnants, and 11% with incomplete occlusion. No
      recanalization or retreatment was performed. The midterm intrastent stenosis rate
      was 57%, of which 60% improved or disappeared, 28% were stable, and 12% led to
      vessel occlusion. Seventy-four percent of stenosis and all vessel occlusions
      occurred with the first-generation Silk stent. CONCLUSIONS: Endovascular
      treatment of complex intracranial aneurysms with the Silk stent is an effective
      therapeutic option. Despite a high rate of delayed complications with the first
      generation stents, the current Silk+ stent appears safer. This treatment achieves
      a high rate of adequate and stable occlusion at long-term follow-up.

PMID- 25376807
TI  - Comparing 3T T1-weighted sequences in identifying hyperintense punctate lesions
      in preterm neonates.
AB  - BACKGROUND AND PURPOSE: The loss of contrast on T1-weighted MR images at 3T may
      affect the detection of hyperintense punctate lesions indicative of
      periventricular leukomalacia in preterm neonates. The aim of the present study
      was to determine which 3T T1-weighted sequence identified the highest number of
      hyperintense punctate lesions and to explore the relationship between the number
      of hyperintense punctate lesions and clinical outcome. MATERIALS AND METHODS: The
      presence of hyperintense punctate lesions was retrospectively evaluated in 200
      consecutive preterm neonates on 4 axial T1-weighted sequences: 3-mm inversion
      recovery and spin-echo and 1- and 3-mm reformatted 3D-fast-field echo.
      Statistically significant differences in the number of hyperintense punctate
      lesions were evaluated by using a linear mixed-model analysis. Logistic
      regression analysis was used to assess the relation between the number of
      hyperintense punctate lesions and neuromotor outcome at 3 months. RESULTS: Thirty
      one neonates had at least 1 hyperintense punctate lesion indicative of
      periventricular leukomalacia in at least 1 of the 4 sequences. The 1-mm axial
      reformatted 3D-fast-field echo sequence identified the greatest number of
      hyperintense punctate lesions (P < .001). No statistically significant
      differences were found among the 3-mm T1-weighted sequences. The greater number
      of hyperintense punctate lesions detected by the 1-mm reformatted T1 3D-fast
      field echo sequence in the central region of the brain was associated with a
      worse clinical outcome. CONCLUSIONS: At 3T, the 1-mm axial reformatted T1 3D-fast
      field echo sequence identified the greatest number of hyperintense punctate
      lesions in the central region of preterm neonate brains, and this number was
      associated with neuromotor outcome.

PMID- 25376808
TI  - Impact of time-to-reperfusion on outcome in patients with poor collaterals.
AB  - BACKGROUND AND PURPOSE: The relationship between reperfusion and clinical outcome
      is time-dependent, and the effect of reperfusion on outcome can vary on the basis
      of the extent of collateral flow. We aimed to identify the impact of time-to
      reperfusion on outcome relative to baseline angiographic collateral grade in
      patients successfully treated with endovascular revascularization for acute large
      vessel anterior circulation stroke. MATERIALS AND METHODS: Two hundred seven
      patients were selected for analysis from our prospectively maintained registry.
      Inclusion criteria were M1 MCA +/- ICA occlusions, onset-to-puncture time within
      8 hours, and successful endovascular reperfusion. Baseline angiographic
      collateral grades were independently evaluated and dichotomized into poor (0-1)
      versus good (2-4). Multivariable analyses were performed to identify the effect
      of collateral-flow adequacy on favorable outcome on the basis of onset-to
      reperfusion time and puncture-to-reperfusion time. RESULTS: In the poor
      collateral group, the odds of favorable outcome significantly dropped for
      patients with onset-to-reperfusion time of >300 minutes or puncture-to
      reperfusion time of >60 minutes (onset-to-puncture time: <=300, 59% versus >300,
      32%; OR, 0.24; P = .011; puncture-to-reperfusion time: <=60, 73% versus >60, 32%;
      OR, 0.21, P = .011), whereas the probability of favorable outcome in the good
      collateral group was not significantly influenced by onset-to-reperfusion time or
      puncture-to-reperfusion time. In the subgroup lesion-volume growth analysis by
      using DWI, the effect of puncture-to-reperfusion time of >60 minutes was
      significantly greater compared with the effect of puncture-to-reperfusion time of
      <60 minutes in the poor collateral group (beta = 41.6 cm(3), P = .001).
      CONCLUSIONS: Time-to-reperfusion including onset-to-reperfusion time and puncture
      to-reperfusion time in patients with poor collaterals is an important limiting
      factor for favorable outcome in a time-dependent fashion. Future trials may
      benefit from a noninvasive imaging technique to detect poor collaterals along
      with a strategy for rapid reperfusion.

PMID- 25376809
TI  - Comparison of modern stroke thrombectomy approaches using an in vitro
      cerebrovascular occlusion model.
AB  - BACKGROUND AND PURPOSE: A new in vitro cerebrovascular occlusion model of the
      intracranial circulation was developed recently for testing thrombectomy devices.
      Using this model, we compared recanalization success associated with different
      modern endovascular thrombectomy approaches. MATERIALS AND METHODS: Model
      experiments were performed in 4 thrombectomy test groups: 1) primary or direct
      Stentriever thrombectomy with a conventional guide catheter (control group), 2)
      primary Stentriever thrombectomy with a balloon-guide catheter, 3) combined
      Stentriever-continuous aspiration approach, and 4) direct aspiration alone.
      Successful recanalization was defined as a TICI score of 2b or 3. RESULTS:
      Seventy-one thrombectomy experiments were conducted. Similar rates of TICI 2b-3
      scores were achieved with balloon-guide and conventional guide catheters (P =
      .34). The combined Stentriever plus aspiration approach and the primary
      aspiration thrombectomy resulted in significantly higher rates of TICI 2b or 3
      than the conventional guide-catheter approach in the control group (P = .008 and
      P = .0001, respectively). The primary Stentriever thrombectomy with the
      conventional guide catheter showed the highest rate of embolization to new
      territories (53%). CONCLUSIONS: Data from our in vitro model experiments show
      that the Stentriever thrombectomy under continuous aspiration and primary
      aspiration thrombectomy approaches led to the highest degree of recanalization.

PMID- 25376810
TI  - MS lesions are better detected with 3D T1 gradient-echo than with 2D T1 spin-echo
      gadolinium-enhanced imaging at 3T.
AB  - BACKGROUND AND PURPOSE: In multiple sclerosis, gadolinium enhancement is used to
      classify lesions as active. Regarding the need for a standardized and accurate
      method for detection of multiple sclerosis activity, we compared 2D-spin-echo
      with 3D-gradient-echo T1WI for the detection of gadolinium-enhancing MS lesions.
      MATERIALS AND METHODS: Fifty-eight patients with MS were prospectively imaged at
      3T by using both 2D-spin-echo and 3D-gradient recalled-echo T1WI in random order
      after the injection of gadolinium. Blinded and independent evaluation was
      performed by a junior and a senior reader to count gadolinium-enhancing lesions
      and to characterize their location, size, pattern of enhancement, and the
      relative contrast between enhancing lesions and the adjacent white matter.
      Finally, the SNR and relative contrast of gadolinium-enhancing lesions were
      computed for both sequences by using simulations. RESULTS: Significantly more
      gadolinium-enhancing lesions were reported on 3D-gradient recalled-echo than on
      2D-spin-echo (n = 59 versus n = 30 for the junior reader, P = .021; n = 77 versus
      n = 61 for the senior reader, P = .017). The difference between the 2 readers was
      significant on 2D-spin-echo (P = .044), for which images were less reproducible
      (kappa = 0.51) than for 3D-gradient recalled-echo (kappa = 0.65). Further
      comparisons showed that there were statistically more small lesions (<5 mm) on 3D
      gradient recalled-echo than on 2D-spin-echo (P = .04), while other features were
      similar. Theoretic results from simulations predicted SNR and lesion contrast for
      3D-gradient recalled-echo to be better than for 2D-spin-echo for visualization of
      small enhancing lesions and were, therefore, consistent with clinical
      observations. CONCLUSIONS: At 3T, 3D-gradient recalled-echo provides a higher
      detection rate of gadolinium-enhancing lesions, especially those with smaller
      size, with a better reproducibility; this finding suggests using 3D-gradient
      recalled-echo to detect MS activity, with potential impact in initiation,
      monitoring, and optimization of therapy.

PMID- 25376811
TI  - Comparison of 3T and 7T susceptibility-weighted angiography of the substantia
      nigra in diagnosing Parkinson disease.
AB  - BACKGROUND AND PURPOSE: Standard neuroimaging fails in defining the anatomy of
      the substantia nigra and has a marginal role in the diagnosis of Parkinson
      disease. Recently 7T MR target imaging of the substantia nigra has been useful in
      diagnosing Parkinson disease. We performed a comparative study to evaluate
      whether susceptibility-weighted angiography can diagnose Parkinson disease with a
      3T scanner. MATERIALS AND METHODS: Fourteen patients with Parkinson disease and
      13 healthy subjects underwent MR imaging examination at 3T and 7T by using
      susceptibility-weighted angiography. Two expert blinded observers and 1
      neuroradiology fellow evaluated the 3T and 7T images of the sample to identify
      substantia nigra abnormalities indicative of Parkinson disease. Diagnostic
      accuracy and intra- and interobserver agreement were calculated separately for 3T
      and 7T acquisitions. RESULTS: Susceptibility-weighted angiography 7T MR imaging
      can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of
      100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease
      with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of
      86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T,
      intraobserver agreement was excellent for experts, and interobserver agreement
      ranged between good and excellent. The less expert reader obtained a diagnostic
      accuracy of 89% at 3T. CONCLUSIONS: Susceptibility-weighted angiography images
      obtained at 3T and 7T differentiate controls from patients with Parkinson disease
      with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing
      Parkinson disease might encourage its use in clinical practice. The use of the
      more accurate 7T should be supported by a dedicated cost-effectiveness study.

PMID- 25376812
TI  - Babies in Distress: Malignant Hyperthermia in Infancy Explored.
AB  - There has been international debate on the infrequent occurrence of malignant
      hyperthermia in infants, where some reports state that this phenomenon does not
      exist in this age group; but the vast majority of studies counteract this
      argument. The proportion of documented cases in the infant population warrants a
      good review of cases and description of symptomatology observed with malignant
      hyperthermia in this cohort. It is paramount for clinicians of the pediatric
      population to recognize patients at risk of having a crisis, and to communicate
      this concern to the surgical/anesthetic team and also to be cognizant of the
      level of care necessary following a crisis. 

PMID- 25376813
TI  - Is waiting room behavior an accurate proxy for families' actual dietary habits? A
      comment regarding "junk food seen at pediatric clinic visits: is it a problem?".

PMID- 25376814
TI  - Incorporating additional targets into learning trials for individuals with autism
      spectrum disorder.
AB  - Recently, researchers have investigated the effectiveness and efficiency of
      presenting secondary targets during learning trials for individuals with autism
      spectrum disorder (ASD). This instructional method may be more efficient than
      typical methods used with learners with ASD, because learners may acquire
      secondary targets without additional instruction. This review will discuss the
      recent literature on providing secondary targets during teaching trials for
      individuals with ASD, identify common aspects and results among these studies,
      and identify areas for future research. 

PMID- 25376816
TI  - [An outstanding partner with physicians in bearing the social responsibility].

PMID- 25376817
TI  - [To achieve optimum asthma control is the core of implementing effective asthma
      management].

PMID- 25376815
TI  - Preconditioning of mesenchymal stem cells for improved transplantation efficacy
      in recessive dystrophic epidermolysis bullosa.
AB  - INTRODUCTION: The use of hematopoietic cell transplantation (HCT) has previously
      been shown to ameliorate cutaneous blistering in pediatric patients with
      recessive dystrophic epidermolysis bullosa (RDEB), an inherited skin disorder
      that results from loss-of-function mutations in COL7A1 and manifests as deficient
      or absent type VII collagen protein (C7) within the epidermal basement membrane.
      Mesenchymal stem cells (MSCs) found within the HCT graft are believed to be
      partially responsible for this amelioration, in part due to their intrinsic
      immunomodulatory and trophic properties and also because they have been shown to
      restore C7 protein following intradermal injections in models of RDEB. However,
      MSCs have not yet been demonstrated to improve disease severity as a stand-alone
      systemic infusion therapy. Improving the efficacy and functional utility of MSCs
      via a pre-transplant conditioning regimen may bring systemic MSC infusions closer
      to clinical practice. METHODS: MSCs were isolated from 2- to 4-week-old mice and
      treated with varying concentrations of transforming growth factor-beta (TGFbeta;
      5-20 ng/mL), tumor necrosis factor- alpha (TNFalpha; 10-40 ng/mL), and stromal
      cell-derived factor 1-alpha (SDF-1alpha; 30 ng/mL) for 24-72 hours. RESULTS: We
      demonstrate that treating murine MSCs with exogenous TGFbeta (15 ng/mL) and
      TNFalpha (30 ng/mL) for 48 hours induces an 8-fold increase in Col7a1 expression
      and a significant increase in secretion of C7 protein, and that the effects of
      these cytokines are both time and concentration dependent. This cytokine
      treatment also promotes a 4-fold increase in Tsg-6 expression, a gene whose
      product is associated with improved wound-healing and immunosuppressive features.
      Finally, the addition of exogenous SDF-1alpha to this regimen induces a
      simultaneous upregulation of Col7a1, Tsg-6, and Cxcr4 expression. CONCLUSIONS:
      These data suggest that preconditioning represents a feasible method for
      improving the functional utility of MSCs in the context of RDEB stem cell
      transplantation, and also highlight the applicability of preconditioning
      principles toward other cell-based therapies aimed at treating RDEB patients.

PMID- 25376818
TI  - [Working together to improve the level of prevention and control of obstructive
      sleep apnea-related stroke in China].

PMID- 25376819
TI  - [Reappraisal of the diagnostic criteria of ventilator-associated pneumonia].

PMID- 25376820
TI  - [An epidemiological survey of current asthma control status in China].
AB  - OBJECTIVE: Base on the China asthma and risk factors epidemiologic investigation
      (CARE study), we analyzed the current status of asthma control in China. METHODS:
      With the multi-stage random cluster sampling method, epidemiological survey was
      performed among Chinese residents who aged over 14 years in 8 provinces (cities)
      from 2010 to 2011. Detailed clinic data of 2 034 asthma patients were collected
      via face-to-face home visit . Asthma was diagnosed based upon the history,
      clinical signs and lung function tests. The SPSS 12.0 was conducted for
      statistics analysis. RESULTS: This survey found that the prevalence rate of
      asthma in China was 1.24% (2 034/164 215), including 973 male and 1 061 female
      patients, with a mean age of (56 +/- 18) years old. Consistent with the Global
      Initiative for Asthma (GINA) guidelines, 40.51% (824/2 034) and 42.58% (866/2
      034) of our patients achieved control and partial control, respectively.
      According to the asthma control test (ACT) estimates, 15.63% (318/2 034) and
      49.46% (1 006/2 034) of patients achieved full control (ACT 25) and well
      control(ACT 20-24), respectively. In the past year, 22.62% (460/2 034) of
      patients reported hospitalized and 26.99% (549/2 034) of patients reported
      emergency room visit at least one time due to asthma exacerbation. 61.80% (1
      257/2 034) of patients were on daily us of medication. Inhaled corticosteroids
      (ICS) plus a long-acting beta2 agonist (LABA) or solely ICS were used in 6.39%
      and 14.75% of patients, respectively. Theophylline treatment accounted for 29.11%
      (592/2 034). Oral glucocorticoid and oral leukotriene modifier (LTRA) treatment
      accounted for 9.49% (193/2 034) and 3.10% (63/2 034), respectively. According to
      the survey, 34.51% (702/2 034) of asthma patients reported a history of smoking .
      The percentage of asthma control in non smoking patients was higher than in
      smoking patients [43.24% (576/1 332) and 35.33% (248/702), respectively].
      Meanwhile, the rates of both hospitalization and emergency due to asthma
      exacerbation in smoking asthma patients were significantly higher than nonsmoking
      asthma patients (27.35% and 31.77%, 20.12% and 24.47%, respectively).
      CONCLUSIONS: The situation of asthma control has been improved in China. However,
      compared with GINA guidelines, there is still a considerable gap. Smoking is one
      of the crucial factors that affect asthma control.

PMID- 25376821
TI  - [Approximate entropy of oxygen saturation and saturation impairment time index
      for the assessment of hypoxemia severity in obstructive sleep apnea hypopnea
      syndrome].
AB  - OBJECTIVE: To explore the clinical significance of two new indexes including
      approximate entropy of oxygen saturation (SpO2ApEn) and saturation impairment
      time index (SITi) in assessing the severity of hypoxemia in obstructive sleep
      apnea hypopnea syndrome (OSAHS) patients. In addition, to investigate the
      correlation betewwn new indexes and other parameters. METHODS: The six hour
      polysomnography (PSG) of 500 patients with OSAHS and snorers in our hospital was
      retrospectively analyzed. According to the level of apnea hypopnea index (AHI) ,
      subjects were divided into four subgroups, namely 113 healthy controls, 121 mild
      OSAHS, 118 moderate OSAHS, and 148 severe OSAHA patients.SpO2ApEn and SITi values
      among the four groups were compared.the correlations between SpO2ApEn, SITi and
      other parameters were analyzed, including AHI, oxygen desaturation index (ODI) ,
      the lowest oxygen saturation (LSpO2) and the duration of oxygen saturation lower
      than 90% (T<90%). Next, taking AHI as the gold standard, the significance of
      SpO2ApEn and SITi in assessing the severity of hypoxemia in OSAHS patients was
      explored by ROC curve analysis. RESULTS: SpO2ApEn and SITi between two each
      groups were significantly different (P < 0.001) and increased synchronously with
      AHI. Spearman correlation analysis showed that SpO2ApEn and SITi had a good
      correlation with AHI (correlation coefficient r = 0.765, r = 0.678, P < 0.01).
      SpO2ApEn and SITi also had a good correlation with ODI, LSpO2and T < 90%.
      According to the ROC analysis, the Boundary values of SpO2ApEn for mild, moderate
      and severe OSAHS patients were 16.70, 17.81, and 20.03, respectively, and the
      corresponding SITi values were 3.685, 4.055, and 4.445. CONCLUSION: In this
      study, SpO2ApEn and SITi increased synchronously with AHI. SpO2ApEn and SITi had
      good correlations with AHI, ODI, LSpO2 and T < 90%. SpO2 ApEn and SITi have
      important clinical significance for assessment of hypoxia severity in OSAHS
      patients.

PMID- 25376822
TI  - [The prevalence of risk factors and status of clinical practice patterns among
      hospitalized patients with acute coronary syndromes].
AB  - OBJECTIVE: To analyze the distribution of multiple risk factors for hospitalized
      patients with acute coronary syndromes (ACS) and explore the status and
      determinants of drug usage recommended by the guideline. METHODS: This was a
      multi-center cross-sectional study in 34 hospitals from 22 provinces in China.
      About ninety ACS patients were consecutively enrolled from each hospital since
      April 15, 2012 according to a standard protocol. Totally, 3 253 patients with
      complete data were analyzed in this study. RESULTS: (1) The average age of male
      patients with ACS was lower than that of female patients (60.4 years vs 66.2
      years, P < 0.01). Nearly 60% of ACS patients were under the age of 65 years.
      Early onset of ACS accounted for one-third of male (< 55 years of age) and two
      fifthes of female patients (< 65 years old). (2) Among the four ACS major risk
      factors (hypertension, hyperlipidemia, smoking and diabetes), hypertension was
      with the highest prevalence (68.4%). More than 90% of ACS patients had at least
      one risk factor and about two-thirds of them had at least two. (3) As for the
      application of evidence-based drugs, the top one was aspirin with 95.3% of ACS
      patients reseiving it. The second was statins (90.1%). Angiotensin converting
      enzyme inhibitors (ACEI) or angiotension II receptor blocker (ARB) was the lowest
      (53.6%). Multivariable analysis indicated that, in contrast to that in ACS
      patients without percutaneous coronary intervention (PCI), the drug usage rates
      were increased by more than 30% for ACEI or ARB and beta receptor blockers, by
      more than 50% for statins, and by 4-7 times for antiplatelet agents among ACS
      patients with PCI. CONCLUSIONS: In China, more than 90% of hospitalized patients
      with ACS carried at least one major risk factor. There is still room for
      improving in the application of drugs recommended by the guidelines, especially
      for ACS patients without PCI.

PMID- 25376823
TI  - [Synergistic effect of hypertension and aging on left atrial volume and
      function].
AB  - OBJECTIVE: To assess the effect of combined hypertension (HT) and aging on left
      atrial (LA) size and phasic function. METHODS: This evaluation was based on the
      data from a cross-sectional study including 738 subjects with high risk for
      cardiovascular disease from an urban community in Beijing. Subjects were divided
      into 3 groups according to age (41-59, 60-69 and >= 70 years) and further into HT
      and non-HT sub-groups. LA volume index were calculated and LA global longitudinal
      strain in late diastole (Sa), early diastole (Se), and total strain (Stot = Sa+
      Se), and strain rate in late diastole (SRa), systole (SRs), and early diastole
      (SRe) were measured using off-line speckle-tracking echocardiography. RESULTS: LA
      volume index increased significantly in HT groups with aging, whereas no changes
      could be viewed in non-HT subjects among all age groups. LA conduit index (Se and
      SRe) decreased with aging in both HT and non-HT subjects with more sever in HT
      subjects than in non-HT subjects in all age groups. The LA conduit index in 41-59
      year-HT, and in 60-69 year-HT subjects were comparable with that in 60-69 year
      non-HT subjects [Se (11.0 +/- 4.4)% vs (11.6 +/- 4.7)%, SRe (1.0 +/- 0.4) s(-1)
      vs (1.0 +/- 0.3) s(-1)], and in >= 70 year-non-HT subjects [Se(10.1 +/- 4.0)% vs
      (9.5 +/- 5.4)%, SRe (0.9 +/- 0.3)s(-1) vs (0.8 +/- 0.4) s(-1)], respectively. LA
      reservoir (Stot and SRs) and contraction (Sa and SRa) index also decreased with
      aging in HT but not in non-HT subjects. CONCLUSIONS: Aging along does not lead to
      LA enlargement in subects, but it does when combined HT. There is synergistic
      effect of HT and aging on LA volume and phasic function.

PMID- 25376824
TI  - [To evaluate the changes in body composition in male human immunodeficiency virus
      related lipodystrophy after different treatment regimens by dual-energy X-ray
      absorptiometry].
AB  - OBJECTIVE: To evaluate the changes of body composition in male patients with
      human immunodeficiency (HIV)-related lipodystrophy (LD) syndrome (HIV-LD)
      switching from stavudine (d4T) to zidovudine (AZT) or tenofovir (TDF) by Dual
      energy X-ray absorptiometry (DXA). METHODS: A total of 47 men with HIV-LD who had
      been exposed to stavudine (d4T) were enrolled in our study from May 2007 to
      September 2013 in Peking Union Medical College Hospital. Twice DXA assessments
      were administrated with interval of at least 12 months. All patients were divided
      into two different treatment regimens, either AZT group switching from d4T to
      zidovudine (AZT) or TDF group switching from d4T to TDF. Parameters of body
      composition in two groups were evaluated by DXA. RESULTS: Compared with baseline
      level, lower limb lean mass increased significantly after treatment [(15.4 +/-
      1.7) kg vs (16.0 +/- 1.7) kg, t = 2.781, P < 0.01] and lower limb fat mass had a
      small decrease(P = 0.05) in AZT group. In TDF group, there were significant
      increases both in upper limb fat mass [(0.6 +/- 0.3) kg vs (1.0 +/- 0.7) kg, t =
      2.422, P < 0.05] and lower limb fat mass [(1.8 +/- 0.8) kg vs (2.6 +/- 1.7) kg, t
      = 2.369, P < 0.05]. In AZT group, change of lower limb fat mass was generally
      small (median -0.04 kg, -4.55%). In TDF group, increase of lower limb fat mass
      and percentage of lower limb fat gain were even greater (median 0.46 kg, 27.41%).
      In a visual comparison of DXA results between AZT and TDF recipients, more fat
      gain of leg fat mass was seen in patients who switched from d4T to TDF (U =
      2.954, P < 0.01). CONCLUSIONS: Compared with AZT group, TDF group led to a more
      increase in leg fat mass. Replacing d4T with TDF translates into an improvement
      of lipodystrophy. Although fat mass did not show a significant increase in AZT
      group, lean mass had improved after switching treatment, indicating AZT as a
      possible alternative agent of d4T. Body composition in men patients with HIV-LD
      can help to adjust the treatment regimen.

PMID- 25376825
TI  - [An analysis of clinical characteristics and risk factors for ulceration in
      ischemic colitis].
AB  - OBJECTIVE: To investigate the clinical manifestations and risk factors related to
      ulcer in patients with ischemic colitis (IC). METHODS: Clinical data of sixty
      three IC patients with definite diagnosis from June 2002 to June 2012 in the PLA
      General Hospital were retrospectively analyzed. All patients were classified into
      ulcer group (23 cases) and non-ulcer group (40 cases) according to the presence
      of ulcer or not. Clinical manifestations and risk factors related to ulcer
      lesions were compared in the two groups. Logistic regression model was used for
      statistical analysis. RESULTS: There were 50 men and 13 women enrolled, with an
      average age of 70 years old. The main clinical manifestations included abdominal
      pain [85.7% (54/63) ], diarrhea [54.0% (34/63)], hematochezia [41.3% (26/63)]. In
      comparison with non-ulcer group, the ulcer group showed higher incidences of
      chronic constipation [34.8% (8/23) vs 12.5% (5/40) , P = 0.03], enteric-coated
      aspirin intake [52.2% (12/23) vs 25.0% (10/40), P = 0.03] and abdomen tenderness
      [82.6% (19/23) vs 52.5% (21/40), P = 0.02]. Chronic constipation and enteric
      coated aspirin intake were independent risk factors related to ulcer lesions (OR
      = 3.38, P = 0.04; OR = 5.91, P = 0.03). Patients with abdomen tenderness had
      higher incidence of ulcer lesion (OR = 3.12, P = 0.04). The most common location
      of IC was left colon [69.8% (44/63)]. No difference of site distribution was
      found in ulcer and non-ulcer group (P = 0.066). Splanchnic atherosclerosis in the
      ulcer group was more common than in non-ulcer group [88.2% (15/17) vs 58.3%
      (14/24), P = 0.038]. The duration of hospitalization was significantly longer in
      ulcer group [ (14.3 +/- 7.1) d vs (6.2 +/- 4.1) d, P < 0.01]. Higher white blood
      cell (WBC) count and lower hemoglobin (Hb) were seen in ulcer group than those in
      non-ulcer group [(10.17 +/- 3.32) *10(9)/L vs (7.25 +/- 3.15)*10(9)/L, P = 0.018;
      (98 +/- 27) g/L vs (126 +/- 35) g/L, P = 0.041]. CONCLUSIONS: Chronic
      constipation, enteric-coated aspirin intake and splanchnic atherosclerosis are
      risk factors related to ulcer in IC patients. Abdomen tenderness, high WBC and
      low Hb strongly indicate possible IC with ulcer.

PMID- 25376826
TI  - [A correlation study of adhesion molecule CD146 and the vulnerability of carotid
      atherosclerotic plaque].
AB  - OBJECTIVE: To investigate the correlation between the expression of adhesion
      molecule CD146 and the vulnerability of carotid atherosclerotic plaque. METHODS:
      The plaque samples were collected from 40 patients who underwent the carotid
      endarterectomy and were divided into the stable plaque group and the instable
      plaque group by ultrasound imaging. Five carotid artery samples were taken from
      the healthy donors as the control. Immunohistochemistry was applied to test the
      CD146 expression in all samples. RESULTS: Higher expression of CD146 was observed
      in the atherosclerotic plaques than in the healthy control. Moreover, statistical
      difference was found in the expression of CD146 in the plaques between the
      instable plaque group and the stable plaque group (0.31 +/- 0.19 vs 0.17 +/-
      0.07, P < 0.05). The expression of CD146 was positively correlated with the
      necrotic area (r = 0.471 8, P = 0.019 9) and the matrix metalloproteinase (MMP)-9
      expression in the plaques (r = 0.535 6, P = 0.000 9). CONCLUSION: The CD146
      expression is correlated with the vulnerability of carotid atherosclerotic
      plaque.

PMID- 25376827
TI  - [The clinical and imaging study of thalamic venous infarction].
AB  - OBJECTIVE: To explore the clinical and radiological features of bilateral
      thalamus venous infarction. METHODS: The cases definitely diagnosed as thalamus
      venous infarction were collected and the corresponding clinical and radiological
      data were retrospectively analyzed. RESULTS: Four cases confirmed as thalamus
      venous infarction by digital substraction angiography (DSA) were collected.
      Bilateral thalamus lesions were detected in all cases by brain MRI scans which
      mainly presented as thalamus edema with high T1 and T2 signals with partial
      enhancement. Mild hemorrage was also shown in one case. Acute or subacute onset
      with clinical manifestations of headache, hypomnesia and hypersomnia were
      reported in all cases. The neurological examination showed conscious disturbance,
      memory impairment and positive Babinski sign. The venous thrombi were formed
      mainly in the transverse and the straight sinuses in 3 cases with the deep
      cerebral venous involved in 2 cases. All patients were improved after the
      anticoagulation therapy. Dural arteriovenous fistula was found in the other case
      drained by the Rosenthal's vein, and the symptoms were ameliorated after the
      embolotherapy. CONCLUSIONS: As the thalamus is drained by the thalamostriate vein
      and the lateral thalamic vein towards the internal cerebral vein with the caudate
      portion drained particularly by the Rosenthal's vein, venous thrombosis or
      fistula drainage into these veins would probably disturb the normal drainage of
      the thalamus and result in further edema and infarction. Thus, the venous
      infarction should be taken into consideration whenever bilateral thalamus lesions
      are encountered in clinical practice and DSA is necessary to confirm the
      diagnosis.

PMID- 25376829
TI  - Incidence trend of esophageal squamous cell carcinoma: an analysis of
      Surveillance Epidemiology, and End Results (SEER) database.

PMID- 25376828
TI  - Intakes of fat and micronutrients between ages 13 and 18 years and the incidence
      of proliferative benign breast disease.
AB  - PURPOSE: Dietary exposures during adolescence may exert important effects on
      breast development and future breast cancer risk. This study evaluated the
      associations between high school intakes of fat and micronutrients and the
      incidence of proliferative benign breast disease (BBD), a marker of increased
      breast cancer risk. METHODS: 29,480 women (mean age 43.3 years, range 33.6-52.9)
      completed a high school food frequency questionnaire in 1998 in the Nurses'
      Health Study II. Between 1991 and 2001, 682 women (follow-up time: 259,828 person
      years) were diagnosed with proliferative BBD whose biopsy slides were reviewed
      and confirmed by the study pathologists. RESULTS: In multivariate Cox
      proportional hazards models, high school intakes of total fat and types of fat
      were not associated with proliferative BBD. Women in the highest quintile of
      total retinol activity equivalents (RAEs), which incorporate retinol, alpha- and
      beta-carotene, and beta-cryptoxanthin intakes, had a 17 % lower risk of
      proliferative BBD than those in the lowest quintile [multivariate hazard ratio
      (HR) 95 % CI 0.83 (0.64, 1.07), p trend = 0.01]; however, additional adjustment
      for high school dietary factors (vitamin D, nuts, and fiber) rendered the
      association nonsignificant [0.99 (0.73, 1.34), p trend = 0.32]. Results were
      similar with additional adjustment for adult RAE intake. Intakes of vitamin E and
      individual carotenoids were not associated with proliferative BBD, although an
      inverse association cannot be ruled out. CONCLUSIONS: In this study, adolescent
      fat and micronutrient intakes were not associated with risk of proliferative BBD.

PMID- 25376830
TI  - Do people know whether they are overweight? Concordance of self-reported,
      interviewer-observed, and measured body size.
AB  - PURPOSE: To evaluate associations among self-reported, interviewer-observed, and
      measured body size in a healthcare setting. METHODS: A total of 543 adult men and
      women undergoing colonoscopy were enrolled into a cross-sectional study conducted
      from 2002 to 2008 at the Johns Hopkins Hospital Outpatient Center. Self-reported
      and interviewer-observed Stunkard body size figure numbers and measured body mass
      index (BMI) were collected and evaluated. The body size figures and BMI were
      categorized as normal weight, overweight, and obese. RESULTS: Correlation between
      self-reported and interviewer-observed body size figure numbers (r = 0.62) was
      lower than the correlation between self-reported (r = 0.72) or interviewer
      observed (r = 0.84) body size figure number and BMI. Participants underestimated
      body size by about one figure compared with the interviewers (mean 0.92 +/-
      1.25). Agreement on normal weight, overweight, and obese between the interviewer
      observed body size figures and BMI categories (kappa = 0.40) was higher than for
      the self-reported body size figures and BMI categories (kappa = 0.23). Among
      participants who judged themselves in the normal weight category by the figures,
      38 and 13 % were overweight and obese, respectively, as measured by BMI. Among
      participants who judged themselves overweight by the body size figures, 57 % were
      obese as measured by BMI. CONCLUSIONS: Although self-reported body size and
      measured body size were well correlated, participants underestimated their body
      size in comparison with interviewers. Many individuals misperceive themselves as
      normal weight when they are overweight or obese by BMI, which may hinder
      prevention and control efforts.

PMID- 25376831
TI  - Evaluation of leptin, thought as a cancer-related biomarker, in postmenopausal
      women.

PMID- 25376832
TI  - Hind limb unloading, a model of spaceflight conditions, leads to decreased B
      lymphopoiesis similar to aging.
AB  - Within the bone marrow, the endosteal niche plays a crucial role in B-cell
      differentiation. Because spaceflight is associated with osteoporosis, we
      investigated whether changes in bone microstructure induced by a ground-based
      model of spaceflight, hind limb unloading (HU), could affect B lymphopoiesis. To
      this end, we analyzed both bone parameters and the frequency of early
      hematopoietic precursors and cells of the B lineage after 3, 6, 13, and 21 d of
      HU. We found that limb disuse leads to a decrease in both bone microstructure and
      the frequency of B-cell progenitors in the bone marrow. Although multipotent
      hematopoietic progenitors were not affected by HU, a decrease in B lymphopoiesis
      was observed as of the common lymphoid progenitor (CLP) stage with a major block
      at the progenitor B (pro-B) to precursor B (pre-B) cell transition (5- to 10-fold
      decrease). The modifications in B lymphopoiesis were similar to those observed in
      aged mice and, as with aging, decreased B-cell generation in HU mice was
      associated with reduced expression of B-cell transcription factors, early B-cell
      factor (EBF) and Pax5, and an alteration in STAT5-mediated IL-7 signaling. These
      findings demonstrate that mechanical unloading of hind limbs results in a
      decrease in early B-cell differentiation resembling age-related modifications in
      B lymphopoiesis.

PMID- 25376833
TI  - IKKalpha is required for the homeostasis of regulatory T cells and for the
      expansion of both regulatory and effector CD4 T cells.
AB  - It was reported that TNF receptor type II signaling, which has the capacity to
      stimulate CD4+ forkhead box P3+ (Foxp3+) regulatory T cells (Tregs), activated
      the noncanonical NF-kappaB pathway in an IKKalpha-dependent manner. Therefore, we
      studied the role of IKKalpha in the homeostasis of Treg population. To this end,
      we generated a mouse strain with conditional knockout of IKKalpha in CD4 cells
      (Ikkalpha(f/f):CD4.Cre) that showed a >60% reduction in the number of Tregs in
      the thymus and peripheral lymphoid tissues, whereas the number of Foxp3- effector
      T cells (Teffs) remained at a normal level. The function of Tregs deficient in
      IKKalpha was examined using Rag1(-/-) mice cotransferred with naive CD4 cells
      (nCD4s). Although wild-type (WT) Tregs inhibited colitis induced by transfer of
      WT nCD4s, IKKalpha-deficient Tregs failed to do so, which was associated with
      their inability to reconstitute Rag1(-/-) mice. Furthermore, nCD4s deficient in
      IKKalpha also failed to reconstitute Rag1(-/-) mice and were defective in
      proliferative responses in vitro and in vivo. Thus, our study reveals a novel
      role of IKKalpha in the maintenance of a normal Treg population and in the
      control of expansion of CD4 T cells. These properties of IKKalpha may be
      exploited as therapeutic strategies in the treatment of major human diseases.

PMID- 25376834
TI  - Autophagy modulates amino acid signaling network in myotubes: differential
      effects on mTORC1 pathway and the integrated stress response.
AB  - Induction of autophagy and the integrated stress response is important for amino
      acid homeostasis. It remains unknown whether the autophagy coregulates both
      mechanistic target of rapamycin complex 1 (mTORC1) signaling and the integrated
      stress response. In mouse C2C12 myotubes, we found that amino acid limitation
      induced autophagy and that the subsequent release of amino acid is required to
      sustain mTORC1 signaling. Inhibition of autophagy by bafilomycin A1 or
      chloroquine treatment during amino acid scarcity abolished mTORC1 signaling, an
      effect that could be rescued by inhibiting protein synthesis or amino acid
      supplementation, respectively. Autophagy is required to sustain the balance of
      both essential and nonessential amino acids during amino acid starvation, and it
      has a predominant role over the ubiquitin-proteasome system in the regulation of
      mTORC1. Inhibition of autophagy was found to activate the integrated stress
      response, as well as eukaryotic initiation factor 2alpha (eIF2alpha) and its
      target genes independent of amino acid availability. Conversely, autophagy
      induction via mTOR inhibition is sufficient to reduce eIF2alpha phosphorylation.
      Thus, autophagy protects the eIF2alpha-mediated stress response independent of
      amino acid supply in cultured myotubes. Our results showed that autophagy
      uniquely modulates mTORC1 and the integrated stress response in an amino acid
      dependent and -independent manner, respectively.

PMID- 25376835
TI  - Reduction of lipid peroxidation products and advanced glycation end-product
      precursors by cyanobacterial aldo-keto reductase AKR3G1-a founding member of the
      AKR3G subfamily.
AB  - The purpose of this study was to investigate the origin and function of the aldo
      keto reductase (AKR) superfamily as enzymes involved in the detoxification of
      xenobiotics. We used the cyanobacterium Synechocystis sp. PCC 6803 as a model
      organism and sequence alignments to find bacterial AKRs with highest identity to
      human enzymes. Disappearance of NADPH was monitored spectrophotometrically to
      calculate enzymatic activity. The molecular weight of the native protein was
      determined by size exclusion chromatography. Substrate docking was performed by
      SwissDock. Sequence alignments identified the NADPH-dependent AKR3G1 having 41.5
      and 40% identity with the human enzymes AKR1B1 and AKR1B10, respectively. Highest
      enzymatic efficiency was observed with 4-oxonon-2-enal (4-ONE; k(cat)/K(m), 561
      s(-1) mM(-1)) and 4-hydroxynonenal (k(cat)/K(m), 26.5 s(-1) mM(-1)),
      respectively. P74308 is the most efficient enzyme for 4-ONE discovered until now.
      Cooperativity of this monomeric enzyme was observed with some substrates. Enzyme
      inactivation or oligomerization as possible explanations for nonhyperbolic enzyme
      kinetics were ruled out by Selwyn's test and gel filtration. The role of the
      little investigated carbonyl-reducing enzymes in detoxification seems to be in
      fact a very old process with rarely observed nonhyperbolic enzyme kinetics as an
      adaptation mechanism to higher concentrations of reactive oxygen species.

PMID- 25376836
TI  - Approaching the next revolution? Evolutionary integration of neural and immune
      pathogen sensing and response.
AB  - Mammalian immunity evolved by the process of natural selection that produced
      differential survival and reproduction advantages through combinations of
      hereditary traits underlying the response to pathogens. Primitive animals sense
      the presence of microbial pathogens through recognition of pathogen-derived
      molecules in their rudimentary immune and nervous systems. No molecular
      biological mechanism assigns primacy of pathogen sensing mechanisms to immune
      cells over neurons. Rather, in animals as diverse as Caenorhabditis elegans to
      mammals, neural reflexes are activated by the presence of pathogens and transduce
      neural mechanisms that control the development of immunity. A coming revolution
      in immunological thinking will require immunologists to incorporate neural
      circuits into understanding pathogen signal transduction, and the molecular
      mechanisms of learning, that culminate in immunity. 

PMID- 25376838
TI  - The importance of clarifying evolutionary terminology across disciplines and in
      the classroom: a reply to Kampourakis.

PMID- 25376837
TI  - Sex-biased gene expression and sexual conflict throughout development.
AB  - Sex-biased gene expression is likely to account for most sexually dimorphic
      traits because males and females share much of their genome. When fitness optima
      differ between sexes for a shared trait, sexual dimorphism can allow each sex to
      express their optimum trait phenotype, and in this way, the evolution of sex
      biased gene expression is one mechanism that could help to resolve intralocus
      sexual conflict. Genome-wide patterns of sex-biased gene expression have been
      identified in a number of studies, which we review here. However, very little is
      known about how sex-biased gene expression relates to sex-specific fitness and
      about how sex-biased gene expression and conflict vary throughout development or
      across different genotypes, populations, and environments. We discuss the
      importance of these neglected areas of research and use data from a small-scale
      experiment on sex-specific expression of genes throughout development to
      highlight potentially interesting avenues for future research. 

PMID- 25376840
TI  - The coordination environment of copper in hair can be altered by treatment
      products.
AB  - OBJECTIVE: To determine whether the coordination environment of copper in hair is
      affected by the shampoo used. METHODS: Electron paramagnetic resonance (EPR)
      spectroscopy to discriminate between mixed oxygen/nitrogen and mixed
      oxygen/sulphur coordination of copper after treatment with two different
      shampoos. RESULTS: Copper with mixed oxygen/nitrogen coordination could be
      converted to mixed oxygen/sulphur coordination by treating with the appropriate
      shampoo, but this was not reversible with the products tested, although copper
      was removed from hair at very high pH values. CONCLUSION: Commercial hair
      treatment products can have a profound effect on the copper coordination
      environment in hair, and this must be taken into account in any attempt to use
      hair as a health marker.

PMID- 25376839
TI  - Changing the peptide specificity of a human T-cell receptor by directed
      evolution.
AB  - Binding of a T-cell receptor (TCR) to a peptide/major histocompatibility complex
      is the key interaction involved in antigen specificity of T cells. The
      recognition involves up to six complementarity determining regions (CDR) of the
      TCR. Efforts to examine the structural basis of these interactions and to exploit
      them in adoptive T-cell therapies has required the isolation of specific T-cell
      clones and their clonotypic TCRs. Here we describe a strategy using in vitro
      directed evolution of a single TCR to change its peptide specificity, thereby
      avoiding the need to isolate T-cell clones. The human TCR A6, which recognizes
      the viral peptide Tax/HLA-A2, was converted to TCR variants that recognized the
      cancer peptide MART1/HLA-A2. Mutational studies and molecular dynamics
      simulations identified CDR residues that were predicted to be important in the
      specificity switch. Thus, in vitro engineering strategies alone can be used to
      discover TCRs with desired specificities. 

PMID- 25376842
TI  - Brief exposure of embryos to steroids or aromatase inhibitor induces sex reversal
      in Nile tilapia (Oreochromis niloticus).
AB  - This study aimed to develop sex reversal procedures targeting the embryonic
      period as tools to study the early steps of sex differentiation in Nile tilapia
      with XX, XY, and YY sexual genotypes. XX eggs were exposed to masculinizing
      treatments with androgens (17alpha-methyltestosterone, 11-ketotestosterone) or
      aromatase inhibitor (Fadrozole), whereas XY and YY eggs were subjected to
      feminizing treatments with estrogen analog (17alpha-ethynylestradiol). All
      treatments consisted of a single or double 4-hr immersion applied between 1 and
      36 hour post-fertilization (hpf). Concentrations of active substances were 1000
      or 2000 MUg l(-1) in XX and XY, and 2000 or 6500 MUg l(-1) in YY. Masculinizing
      treatments of XX embryos achieved a maximal sex reversal rate of 10% with an
      exposure at 24 hpf to 1000 MUg l(-1) of 11-ketotestosterone or to 2000 MUg l(-1)
      of Fadrozole. Feminization of XY embryos was more efficient and induced up to 91%
      sex reversal with an exposure to 2000 MUg l(-1) of 17alpha-ethynylestradiol.
      Interestingly, similar treatments failed to reverse YY fish to females,
      suggesting either that a sex determinant linked to the Y chromosome prevents the
      female pathway when present in two copies, or that a gene present on the X
      chromosome is needed for the development of a female phenotype.

PMID- 25376841
TI  - Body composition, hemodynamic, and biochemical parameters of young female normal
      weight oligo-amenorrheic and eumenorrheic athletes and nonathletes.
AB  - AIMS: Low-weight hypogonadal conditions such as anorexia nervosa are associated
      with marked changes in body composition, hemodynamic and hematological
      parameters, and liver enzymes. The impact of athletic activity in normal-weight
      adolescents with/without amenorrhea on these parameters has not been assessed.
      Our aim was to examine these parameters in normal-weight athletes and nonathletes
      and determine any associations with body composition, oligo-amenorrhea, and
      exercise intensity. METHODS: We assessed vital signs, complete blood counts,
      liver enzymes, and regional body composition in 43 oligo-amenorrheic athletes
      (OAA), 24 eumenorrheic athletes (EA), and 23 nonathletes aged 14-21 years.
      RESULTS: The BMI was lower in OAA than in EA. Systolic and pulse pressure and
      temperature were lowest in OAA. Blood counts did not differ among groups.
      Aspartate aminotransferase (AST) was higher in both groups of athletes, while
      alanine aminotransferase (ALT) was higher in OAA than in EA and nonathletes.
      Total and regional fat were lower in OAA than in other groups, and these factors
      were associated positively with heart rate and inversely with liver enzymes.
      CONCLUSIONS: Athletic activity is associated with higher AST levels, whereas
      menstrual dysfunction is associated with lower total and regional fat and higher
      ALT levels. Higher liver enzymes are associated with reductions in total and
      regional fat.

PMID- 25376843
TI  - UbcH10 overexpression increases carcinogenesis and blocks ALLN susceptibility in
      colorectal cancer.
AB  - Cyclins are essential for cell proliferation, the cell cycle and tumorigenesis in
      all eukaryotes. UbcH10 regulates the degradation of cyclins in a ubiquitin
      dependent manner. Here, we report that UbcH10 is likely involved in
      tumorigenesis. We found that cancer cells exposed to n-acetyl-leu-leu-norleucinal
      (ALLN) treatment and UbcH10 depletion exhibit a synergistic therapeutic effect.
      Abundant expression of UbcH10 drives resistance to ALLN-induced cell death, while
      cells deficient in UbcH10 were susceptible to ALLN-induced cell death. The
      depletion of UbcH10 hindered tumorigenesis both in vitro and in vivo, as assessed
      by colony formation, growth curve, soft agar and xenograft assays. These
      phenotypes were efficiently rescued through the introduction of recombinant
      UbcH10. In the UbcH10-deficient cells, alterations in the expression of cyclins
      led to cell cycle changes and subsequently decreases in tumorigenesis. The
      tumorigenesis of xenograft tumors from UbcH10-deficient cells treated with ALLN
      was decreased relative to wild-type cells treated with ALLN in nude mice. On the
      molecular level, we observed that UbcH10 deficiency enhances the activation of
      caspase 8 and caspase 3 but not caspase 9 to impair cell viability upon ALLN
      treatment. Collectively, our results suggest that, as an oncogene, UbcH10 is a
      potential drug target for the treatment of colorectal cancer. 

PMID- 25376844
TI  - Different fingerprinting strategies to differentiate Porana sinensis and plants
      of Erycibe by high-performance liquid chromatography with diode array detection,
      ultra high performance liquid chromatography with tandem quadrupole mass
      spectrometry, and chemometrics.
AB  - Plants of Erycibe are widely used in traditional Chinese medicine for the
      treatment of joint pain and rheumatoid arthritis. With the reduction of Erycibe
      resources in the wild, Porana sinensis has been widely used as a substitute.
      However, it is important to understand the chemical distinctions between the two
      kinds of plants and identify their individual chemical markers. In this study,
      multiwavelength chromatographic fingerprint and precursor ion fingerprint
      techniques were used in conjunction with chemometric tools to fingerprint and
      thus differentiate between plant samples. The similar results obtained from
      different fingerprints prove the reliability of the two fingerprints. Results
      obtained from principal component analysis and orthogonal projection to latent
      structures discriminant analysis identified similarities between the chemical
      components of P. sinensis and plants of Erycibe. However, concentrations of 4
      caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and
      4,5-dicaffeoylquinic acid were higher in P. sinensis than in plants of Erycibe,
      suggesting that P. sinensis may be more effective in medical treatments of some
      diseases than Erycibe. 

PMID- 25376845
TI  - The Unique Binding Mode of Laulimalide to Two Tubulin Protofilaments.
AB  - Laulimalide, a cancer chemotherapeutic in preclinical development, has a unique
      binding site located on two adjacent beta-tubulin units between tubulin
      protofilaments of a microtubule. Our extended protein model more accurately
      mimics the microtubule environment, and together with a 135 ns molecular dynamics
      simulation, identifies a new binding mode for laulimalide, which differs from the
      modes presented in work using smaller protein models. The new laulimalide-residue
      interactions that are computationally revealed explain the contacts observed via
      independent mass shift perturbation experiments. The inclusion of explicit
      solvent shows that many laulimalide-tubulin interactions are water mediated. The
      new contacts between the drug and the microtubule structure not only improve our
      understanding of laulimalide binding but also will be essential for efficient
      derivatization and optimization of this prospective cancer chemotherapy agent.
      Observed changes in secondary protein structure implicate the S7-H9 loop (M-loop)
      and H1'-S2 loop in the mechanism by which laulimalide stabilizes microtubules to
      exert its cytotoxic effects. 

PMID- 25376846
TI  - Circulating myeloid-derived suppressor cells correlate with clinical outcome in
      Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy.
AB  - In the attempt to find a peripheral blood biological marker that could mirror the
      dysregulated microenvironment of Hodgkin Lymphoma (HL), we analysed the amount of
      myeloid-derived suppressor cells (MDSC), including the three main sub-types
      (monocytic, granulocytic and CD34 + fraction). The absolute MDSC count was
      investigated in 60 consecutive newly diagnosed HL patients and correlated with
      clinical variables at diagnosis and outcome. Patients received standard-of-care
      chemotherapy with the exception of interim fluorodeoxyglucose positron emission
      tomography (PET-2)-positive patients, who were switched early to a salvage
      regimen. All MDSC subsets were increased in HL patients compared to normal
      subjects (P < 0.0001) and were higher in non-responders. However, a strong
      prognostic significance was limited to immature (CD34(+) ) MDSC. A cut-off level
      of 0.0045 * 10(9) /l for CD34(+) MDSC resulted in 89% (95% confidence interval
      [CI] 52-99%) sensitivity and 92% (95% CI 81-98%) specificity. The positive
      predictive value to predict progression-free survival was 0.90 for PET-2 and 0.98
      for CD34(+) MDSC count; the negative predictive value was 0.57 for PET-2 and 0.73
      for CD34(+) MDSC. PFS was significantly shorter in patients with more than 0.0045
      * 10(9) CD34(+) MDSC cells/l at diagnosis and/or PET-2 positivity (P < 0.0001).
      In conclusion, all circulating MDSC subsets are increased in HL; CD34(+) MDSC
      predict short PFS, similarly to PET-2 but with the advantage of being available
      at diagnosis.

PMID- 25376848
TI  - Electrocatalysts: Facile Construction of Pt-Co/CNx Nanotube Electrocatalysts and
      Their Application to the Oxygen Reduction Reaction (Adv. Mater. 48/2009).
AB  - Pt-Co alloyed nanoparticles can be facilely immobilized onto CNx nanotubes due to
      the incorporated nitrogen, report Yanwen Ma, Zheng Hu, and co-workers on p. 4953.
      The as-prepared electrocatalysts exhibit good performance for oxygen reduction
      reactions in acidic media arising from the high dispersion and alloying effect of
      Pt-Co nanoparticles, as well as the intrinsic catalytic capacity of CNx
      nanotubes, which is significant for the development of fuel cells. 

PMID- 25376847
TI  - Prevalence of peripheral artery disease in the elderly population in urban and
      rural areas of Central Africa: the EPIDEMCA study.
AB  - OBJECTIVE: Data on peripheral artery disease in Africa are sparse and limited to
      urban areas. Given the urban/rural socio-economical gradient in these countries,
      we sought to determine the prevalence and risk factors of peripheral artery
      disease in urban and rural areas of two countries in Central Africa. METHODS:
      Individuals >=65 years old living in two urban and rural areas of the Republic of
      Central Africa (ROC) and the Central African Republic (CAR) were invited.
      Demographic, clinical and biological data were collected. Ankle-brachial index
      <=0.90 defined peripheral artery disease. RESULTS: Among the 1871 participants
      (age 73 years, 62% female) the prevalence of peripheral artery disease was 14.8%,
      higher in ROC than in CAR (17.4% vs. 12.2%, p = 0.007) and higher in females than
      males (16.6% vs. 11.9%, p = 0.012). The prevalence of peripheral artery disease
      increased with age, respectively at 10.9%, 14.9%, 15.1% and 22.2% for age bands
      of 65-69, 70-74, 75-79 and 80+years (p < 0.001). Higher rates of peripheral
      artery disease were found in urban areas in ROC (20.7% vs. 14.4% in rural areas,
      p = 0.011), but not in CAR (11.5% vs. 12.9%, p = NS). In multivariate analysis,
      peripheral artery disease was significantly associated with age (odds ratio (OR):
      1.03; p = 0.004), dyslipidaemia (OR: 1.88; p = 0.003), smoking (OR: 1.78; p =
      0.003), obesity (OR: 1.98; p = 0.034) and underweight (OR: 1.49; p = 0.023).
      Regular alcohol drinking was associated with decreased risk of peripheral artery
      disease (OR: 0.73; p = 0.044). CONCLUSION: The prevalence of peripheral artery
      disease in the elderly is high in Africa, especially in females. In ROC, with a
      higher urban-rural socio-economic gradient, peripheral artery disease is more
      frequent in the urban areas.

PMID- 25376849
TI  - Chitinophaga longshanensis sp. nov., a mineral-weathering bacterium isolated from
      weathered rock.
AB  - A Gram-stain-negative, aerobic, yellow-pigmented, non-motile, non-spore-forming,
      rod-shaped bacterial strain, Z29(T), was isolated from the surface of weathered
      rock (potassic trachyte) from Nanjing, Jiangsu Province, PR China. Phylogenetic
      analysis based on 16S rRNA gene sequences suggested that strain Z29(T) belongs to
      the genus Chitinophaga in the family Chitinophagaceae. Levels of 16S rRNA gene
      sequence similarity between strain Z29(T) and the type strains of recognized
      species of the genus Chitinophaga ranged from 92.7 to 98.2 %. The main fatty
      acids of strain Z29(T) were iso-C15 : 0, C16 : 1omega5c and iso-C17 : 0 3-OH. It
      also contained menaquinone 7 (MK-7) as the respiratory quinone and homospermidine
      as the main polyamine. The polar lipid profile contained
      phosphatidylethanolamine, unknown aminolipids, unknown phospholipids and unknown
      lipids. The total DNA G+C content of strain Z29(T) was 51.3 mol%. Phenotypic
      properties and chemotaxonomic data supported the affiliation of strain Z29(T)
      with the genus Chitinophaga. The low level of DNA-DNA relatedness (ranging from
      14.6 to 29.8 %) to the type strains of other species of the genus Chitinophaga
      and differential phenotypic properties demonstrated that strain Z29(T) represents
      a novel species of the genus Chitinophaga, for which the name Chitinophaga
      longshanensis sp. nov. is proposed. The type strain is Z29(T) ( = CCTCC AB
      2014066(T) = LMG 28237(T)).

PMID- 25376850
TI  - Phyllobacterium sophorae sp. nov., a symbiotic bacterium isolated from root
      nodules of Sophora flavescens.
AB  - Two novel Gram-stain-negative strains (CCBAU 03422(T) and CCBAU 03415) isolated
      from root nodules of Sophora flavescens were classified phylogenetically into the
      genus Phyllobacterium based on the comparative analysis of 16S rRNA and atpD
      genes. They showed 99.8 % rRNA gene sequence similarities to Phyllobacterium
      brassicacearum LMG 22836(T), and strain CCBAU 03422(T) showed 91.2 and 88.6 %
      atpD gene sequence similarities to strains Phyllobacterium endophyticum LMG
      26470(T) and Phyllobacterium brassicacearum LMG 22836(T), respectively. Strain
      CCBAU 03422(T) contained Q-10 as its major quinone and showed a cellular fatty
      acid profile, carbon source utilization and other phenotypic characteristics
      differing from type strains of related species. DNA-DNA relatedness (lower than
      48.8 %) further confirmed the differences between the novel strains and the type
      strains of related species. Strain CCBAU 03422(T) could nodulate and fix nitrogen
      effectively on its original host plant, Sophora flavescens. Based upon the
      results mentioned above, a novel species named Phyllobacterium sophorae is
      proposed and the type strain is CCBAU 03422(T) ( = A-6-3(T) = LMG 27899(T) =
      HAMBI 3508(T)).

PMID- 25376851
TI  - Muriicola marianensis sp. nov., isolated from seawater.
AB  - A Gram-stain-negative, aerobic, orange-pigmented, rod-shaped and non-motile
      bacterium, designated strain A6B8(T), was isolated from seawater of the Mariana
      Trench. The isolate grew at 4-50  degrees C (optimum 30-35  degrees C), at pH 6.5
      8.0 (optimum pH 7.5) and with 0.5-4.0 % (w/v) NaCl (optimum 1.0-2.0 %).
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain
      A6B8(T) was related most closely to the genus Muriicola and shared highest
      sequence similarity of 97.7 % with Muriicola jejuensis EM44(T). Chemotaxonomic
      analysis showed menaquinone 6 (MK-6) was the predominant isoprenoid and iso-C15 :
      0, iso-C15 : 1 G and iso-C17 : 0 3-OH were the major cellular fatty acids. The
      polar lipid profile of strain A6B8(T) included phosphatidylethanolamine, three
      unidentified aminolipids and four unidentified lipids. The genomic DNA G+C
      content was 47.1 mol%. The DNA-DNA relatedness value (23.3 %) clearly
      demonstrated that strains A6B8(T) and M. jejuensis EM44(T) were representatives
      of two different species. Based on the phenotypic, phylogenetic and
      chemotaxonomic characterizations, A6B8(T) ( = CGMCC 1.12606(T) = KCTC 32436(T))
      is considered to be the type strain of a novel species of the genus Muriicola,
      for which the name Muriicola marianensis sp. nov. is proposed.

PMID- 25376852
TI  - Rhizobium yantingense sp. nov., a mineral-weathering bacterium.
AB  - A Gram-stain-negative, rod-shaped bacterial strain, H66(T), was isolated from the
      surfaces of weathered rock (purple siltstone) found in Yanting, Sichuan Province,
      PR China. Cells of strain H66(T) were motile with peritrichous flagella.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain
      H66(T) belongs to the genus Rhizobium. It is closely related to Rhizobium
      huautlense SO2(T) (98.1 %), Rhizobium alkalisoli CCBAU 01393(T) (98.0 %) and
      Rhizobium cellulosilyticum ALA10B2(T) (98.0 %). Analysis of the housekeeping
      genes, recA, glnII and atpD, showed low levels of sequence similarity (<92.0 %)
      between strain H66(T) and other recognized species of the genus Rhizobium. The
      predominant components of the cellular fatty acids were summed feature 8 (C18 :
      1omega7c and/or C18 : 1omega6c) and C16 : 0. The G+C content of strain H66(T) was
      60.3 mol%. Strain H66(T) is suggested to be a novel species of the genus
      Rhizobium based on the low levels of DNA-DNA relatedness (ranging from 14.3 % to
      40.0 %) with type strains of species of the genus Rhizobium and on its unique
      phenotypic characteristics. The namehttp://dx.doi.org/10.1601/nm.1279Rhizobium
      yantingense sp. nov. is proposed for this novel species. The type strain is
      H66(T) ( = CCTCC AB 2014007(T) = LMG 28229(T)).

PMID- 25376853
TI  - Stuck on me--Dupuytren's disease of the finger presenting as complete synechium
      of the finger to the palm.

PMID- 25376855
TI  - Velocimetry in microchannels using photobleached molecular tracers: a tool to
      discriminate solvent velocity in flows of suspensions.
AB  - We report the development and analysis of a velocimetry technique based on the
      short time displacement of molecular tracers, tagged thanks to photobleaching. We
      use confocal microscopy to achieve a good resolution transverse to the
      observation field in the direction of the velocity gradient. The intensity
      profiles are fitted by an approximate analytical model which accounts for
      hydrodynamic dispersion, and allow access to the local velocity. The method is
      validated using pressure driven flow in microfluidic slits having a thickness of
      a few tens of micrometers. We discuss the main drawbacks of this technique which
      is an overestimation of the velocity close to the walls due to the combination of
      molecular diffusion and shear. We demonstrate that this error, limited to a near
      wall region of a few micrometers thick, could be controlled by limiting the
      diffusion of fluorophore molecules or minimizing the bleaching time. The
      presented technique could be combined with standard particle imaging velocimetry
      to access velocity differences and allow particle trajectory analysis in
      microflows of suspensions. 

PMID- 25376854
TI  - Withaferin A abolishes the stem cell factor-stimulated pigmentation of human
      epidermal equivalents by interrupting the auto-phosphorylation of c-KIT in human
      melanocytes.
AB  - We characterized the mechanism(s) underlying the abrogating effect of withaferin
      A (WFA) on the stem cell factor (SCF)-stimulated pigmentation of human epidermal
      equivalents (HEEs). Increased gene and protein expression levels of tyrosinase,
      tyrosinase-related protein1, dopachrome tautomerase, PMEL17, c-KIT and their
      targeted transcription factor, microphthalmia-associated transcription factor
      (MITF) were significantly reversed at days 7 and 10, respectively, by treatment
      with WFA. In WFA-treated normal human melanocytes (NHMs), there was a marked
      deficiency in the SCF-stimulated series of phosphorylations of c-KIT, Shc, Raf-1,
      MEK, ERK, MITF and CREB. Treatment with dithiothreitol (DTT) distinctly abolished
      the suppressive effect of WFA on the SCF-stimulated phosphorylation of c-KIT in
      NHMs. On the other hand, even after incubation at 4  degrees C for 2 h with 5 nM
      SCF, followed by the removal of unbound SCF by washing and then raising the
      temperature to 37  degrees C to start the signaling reaction, c-KIT was
      distinctly phosphorylated to a similar extent by incubation for 15 min with SCF
      only or with SCF + WFA. These findings indicate that WFA attenuates the SCF
      induced activation of c-KIT in NHMs by interrupting the auto-phosphorylation of c
      KIT through DTT-suppressible Michael addition thioalkylation reactions without
      interrupting the binding of SCF to the c-KIT receptor.

PMID- 25376856
TI  - The use of, and attitudes towards, electronic cigarettes and self-reported
      exposure to advertising and the product in general.
AB  - OBJECTIVE: Very few studies have investigated New Zealanders' use of, and
      attitudes towards, e-cigarettes, their exposure to e-cigarette advertising and
      their general exposure to this product. The current study aims to fill this
      information gap. METHODS: Responses were gathered from a sample of adult smokers
      and recent quitters who took part in a fortnightly computer-assisted telephone
      interviewing survey. This paper reports on data collected in 2013 on the use of,
      and attitudes towards, e-cigarettes and exposure to advertising and the product
      in general. Responses were compared by socio-demographic status and recent quit
      attempts. RESULTS: Between 23% and 39% of respondents reported having used e
      cigarettes (with the highest level among those who had quit or tried to quit
      recently), and 8-16% had used e-cigarettes in the past two weeks. About one half
      reported seeing advertising of e-cigarettes in the past two weeks, 22-41% had
      seen people they knew using e-cigarettes and 10-15% had seen a stranger using
      them in the past two weeks. Attitudinal responses are reported in the main text.
      CONCLUSIONS: The rate of ever-use suggested that smokers and recent quitters are
      receptive to e-cigarettes and that they were available to many of them to try.
      Exposure to e-cigarette advertising or the product in general was not uncommon.
      Future studies should continue monitor the use of e-cigarettes and investigate
      the impact of the exposure to people's attitudes towards the product and their
      subsequent use of e-cigarettes.

PMID- 25376857
TI  - In-office biopsy of upper airway lesions: safety, tolerance, and effect on time
      to treatment.
AB  - OBJECTIVES/HYPOTHESIS: Definitive tissue diagnosis for lesions warranting biopsy
      is shifting from the operating room to the office. Safety, tolerance, factors
      related to successful biopsy, and time to treatment are not well-defined.
      METHODS: Retrospective review of 116 patients undergoing in-office biopsy of
      oropharynx, larynx, or hypopharynx were included. Logistic regression determined
      if demographics, site, T-stage, or approach (transoral/transnasal) were related
      to success. Time to definitive treatment was also analyzed. RESULTS: Ninety-two
      transnasal and 24 transoral biopsies were performed on 73 laryngeal, 35
      oropharyngeal, and 8 hypopharyngeal lesions. Of those, 97 of 116 diagnoses were
      made in-office. There were no complications; two patients did not tolerate the
      procedure. Success was not related to age (P = 0.374), site (P = 0.527), T-stage
      (P = 0.587), or approach (P = 0.566). Time to treatment was 24.2 +/- 13.9 days
      with successful office biopsy and 48.8 +/- 49.4 days without. CONCLUSIONS: High
      procedural completion rate was observed across patients, sites, and approaches.
      All patients should be considered for in-office biopsy, a more time- and cost
      effective option leading to earlier treatment.

PMID- 25376858
TI  - Patients' expectations, satisfaction, and quality of life with immediate loading
      protocol.
AB  - OBJECTIVES: To examine patients' expectations, the level of satisfaction, and the
      oral health-related quality of life (OHRQoL) with regard to the implants'
      immediate loading protocol (ILP) in edentate individuals. METHODS: This pilot
      trial used a pre-post design to assess patient-centered outcomes in 18 edentate
      individuals (mean age 62.4 +/- 7.7 years) who have received a 2-implant
      (unsplinted) mandibular overdenture through an ILP. Visual analog scales, the
      McGill denture satisfaction questionnaire, and the oral health impact profile
      (OHIP-20) questionnaire were used to evaluate patients' expectations,
      satisfaction, and OHRQoL at baseline, 2 weeks, 1 month, and 4 months after
      surgery. Personality trait and socio-demographic information were obtained using
      the revised NEO personality inventory and a self-administered questionnaire,
      respectively. Non-parametric methods and Brunner-Langer approach were used to
      analyze the data. RESULTS: The participants had a wide range of expectations
      regarding the ILP. Expectations included short-term positive impact on aesthetics
      (83.3%) and social life (55.7%), as well as negative effects on comfort (5.6%),
      the ability to chew (11.1%), and the ability to clean the lower denture (11.1%).
      The ILP satisfied 94.4% of the participants, regardless of socio-demographic and
      personality profiles. There was a statistically significant improvement in
      overall satisfaction, comfort, perceived aesthetics, stability of the
      overdenture, and ability to chew from baseline to 2-week, 1-, and 4-month follow
      up (P < 0.001). There was 100% agreement among patients on recommending this
      procedure to others. There was a statistically significant decrease in the total
      OHIP scores and all its domains (P < 0.001) from baseline to 2 weeks. These
      differences remained statistically significant at 4-month follow-up. The ILP
      improved patients' OHRQoL, regardless of the implant loss, the socio-demographic
      characteristics, and personality traits. CONCLUSIONS: The ILP of two unsplinted
      implants with a mandibular overdenture significantly improved satisfaction and
      short-term OHRQoL, and appears to meet expectations in edentulous elders. There
      was 100% agreement among patients on recommending this procedure to others.

PMID- 25376859
TI  - Ocular complications in robotic surgery.
AB  - BACKGROUND: The penetration of robotic technology in various surgical fields may
      increase ocular complications. METHODS: A systematic search was performed in both
      PubMed and Scopus databases. RESULTS: Eight articles were retrieved by the
      literature search. In total, 142 patients were included in the study. The most
      frequent complication was increased intra-ocular pressure. Corneal abrasion,
      ischaemic optic neuropathy and postoperative visual loss were also reported. The
      duration of operations was 1.7-9.9 h; mean intra-ocular pressure was 3.6-13.3
      mmHg; estimated blood loss was 29.7-1200 ml; and administered intravenous fluids
      were 1.600-4.300 ml. CONCLUSIONS: Meticulous preoperative ophthalmological
      assessment, restriction of intravenous fluids, 'rest stops', eyelid taping and
      ocular dressings are the major protective measures suggested by the literature.
      Collaboration between the surgical team and the anaesthetist is also essential.
      Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25376860
TI  - Titanium cis-1,2-diaminocyclohexane (cis-DACH) salalen catalysts for the
      asymmetric epoxidation of terminal non-conjugated olefins with hydrogen peroxide.
AB  - Chiral Ti salalen complexes catalyze the asymmetric epoxidation of terminal non
      conjugated olefins with hydrogen peroxide. Modular ligands based on cis-1,2
      diamino-cyclohexane (cis-DACH) were developed, giving high yields and
      enantiomeric excesses (ee, up to 96 %) at catalyst loadings as low as 0.1-0.5 mol
      %, and even under solvent-free conditions. 

PMID- 25376863
TI  - Volumetric mammographic density: heritability and association with breast cancer
      susceptibility loci.
AB  - BACKGROUND: Mammographic density is a strong heritable trait, but data on its
      genetic component are limited to area-based and qualitative measures. We studied
      the heritability of volumetric mammographic density ascertained by a fully
      automated method and the association with breast cancer susceptibility loci.
      METHODS: Heritability of volumetric mammographic density was estimated with a
      variance component model in a sib-pair sample (N pairs = 955) of a Swedish
      screening based cohort. Associations with 82 established breast cancer loci were
      assessed in an independent sample of the same cohort (N = 4025 unrelated women)
      using linear models, adjusting for age, body mass index, and menopausal status.
      All tests were two-sided, except for heritability analyses where one-sided tests
      were used. RESULTS: After multivariable adjustment, heritability estimates
      (standard error) for percent dense volume, absolute dense volume, and absolute
      nondense volume were 0.63 (0.06) and 0.43 (0.06) and 0.61 (0.06), respectively
      (all P < .001). Percent and absolute dense volume were associated with rs10995190
      (ZNF365; P = 9.0 * 10(-6) and 8.9 * 10(-7), respectively) and rs9485372 (TAB2; P
      = 1.8 * 10(-5) and 1.8 * 10(-3), respectively). We also observed associations of
      rs9383938 (ESR1) and rs2046210 (ESR1) with the absolute dense volume (P = 2.6 *
      10(-4) and 4.6 * 10(-4), respectively), and rs6001930 (MLK1) and rs17356907
      (NTN4) with the absolute nondense volume (P = 6.7 * 10(-6) and 8.4 * 10(-5),
      respectively). CONCLUSIONS: Our results support the high heritability of
      mammographic density, though estimates are weaker for absolute than percent dense
      volume. We also demonstrate that the shared genetic component with breast cancer
      is not restricted to dense tissues only.

PMID- 25376862
TI  - Expanding access to BRCA1/2 genetic counseling with telephone delivery: a cluster
      randomized trial.
AB  - BACKGROUND: The growing demand for cancer genetic services underscores the need
      to consider approaches that enhance access and efficiency of genetic counseling.
      Telephone delivery of cancer genetic services may improve access to these
      services for individuals experiencing geographic (rural areas) and structural
      (travel time, transportation, childcare) barriers to access. METHODS: This
      cluster-randomized clinical trial used population-based sampling of women at risk
      for BRCA1/2 mutations to compare telephone and in-person counseling for: 1)
      equivalency of testing uptake and 2) noninferiority of changes in psychosocial
      measures. Women 25 to 74 years of age with personal or family histories of breast
      or ovarian cancer and who were able to travel to one of 14 outreach clinics were
      invited to participate. Randomization was by family. Assessments were conducted
      at baseline one week after pretest and post-test counseling and at six months. Of
      the 988 women randomly assigned, 901 completed a follow-up assessment. Cluster
      bootstrap methods were used to estimate the 95% confidence interval (CI) for the
      difference between test uptake proportions, using a 10% equivalency margin.
      Differences in psychosocial outcomes for determining noninferiority were
      estimated using linear models together with one-sided 97.5% bootstrap CIs.
      RESULTS: Uptake of BRCA1/2 testing was lower following telephone (21.8%) than in
      person counseling (31.8%, difference = 10.2%, 95% CI = 3.9% to 16.3%; after
      imputation of missing data: difference = 9.2%, 95% CI = -0.1% to 24.6%).
      Telephone counseling fulfilled the criteria for noninferiority to in-person
      counseling for all measures. CONCLUSIONS: BRCA1/2 telephone counseling, although
      leading to lower testing uptake, appears to be safe and as effective as in-person
      counseling with regard to minimizing adverse psychological reactions, promoting
      informed decision making, and delivering patient-centered communication for both
      rural and urban women.

PMID- 25376861
TI  - Circulating biomarkers of one-carbon metabolism in relation to renal cell
      carcinoma incidence and survival.
AB  - BACKGROUND: The etiology of renal cell carcinoma (RCC) is only partially
      understood, but a metabolic component appears likely. We investigated biomarkers
      of one-carbon metabolism and RCC onset and survival. METHODS: The European
      Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385747
      participants with blood samples between 1992 and 2000, and this analysis included
      556 RCC case-control pairs. A subsequent replication study included 144 case
      control pairs nested within the Melbourne Collaborative Cohort Study (MCCS).
      Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine
      and homocysteine were measured in prediagnostic samples and evaluated with
      respect to RCC risk using conditional and unconditional logistic regression
      models, and to all-cause mortality in RCC cases using Cox regression models. All
      statistical tests were two-sided. RESULTS: EPIC participants with higher plasma
      concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the
      4(th) and 1(st) quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28
      to 0.57, P trend < .001. We found similar results after adjusting for potential
      confounders (adjusted P trend < .001). In survival analysis, the hazard ratio for
      all-cause mortality in RCC cases when comparing the 4(th) and 1(st) quartiles
      (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P trend < .001).
      Subsequent replication of these associations within the MCCS yielded very similar
      results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P trend = .07)
      and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P trend = .02). No
      association was evident for the other measured biomarkers. CONCLUSION: Study
      participants with higher circulating concentrations of vitamin B6 had lower risk
      of RCC and improved survival following diagnosis in two independent cohorts.

PMID- 25376864
TI  - Advances in an active and passive targeting to tumor and adipose tissues.
AB  - INTRODUCTION: Data reported during the last decade of the twentieth century
      indicate that passive targeting is an efficient strategy for delivering
      nanocarrier systems to tumor tissues. The focus of this review is on active
      targeting as a next-generation strategy for extending the capacity of a drug
      delivery system (DDS). AREAS COVERED: Tumor vasculature targeting was achieved
      using arginine- glycine-aspartic acid, asparagine-glycine-arginine and other
      peptides, which are well-known peptides, as ligand against tumor vasculature. An
      efficient system for delivering small interfering RNA to the tumor vasculature
      involved the use of a multifunctional envelope-type nanodevice based on a pH
      modified cationic lipid and targeting ligands. The active-targeting system was
      extended from tumor delivery to adipose tissue delivery, where endothelial cells
      are tightly linked and are impermeable to nanocarriers. In mice, prohibitin
      targeted nanoparticles can be used to successfully deliver macromolecules to
      induce anti-obese effects. Finally, the successful delivery of nanocarriers to
      adipose tissue in obese mice via the enhanced permeability and retention-effect
      is reported, which can be achieved in tumor tissue. EXPERT OPINION: Unlike tumor
      tissues, only a few reports have appeared on how liposomal carriers accumulate in
      adipose tissues after systemic injection. This finding, as well as active
      targeting to the adipose vasculature, promises to extend the capacity of DDS to
      adipose tissue. Since the site of action of nucleic acids is the cytosol, the
      intracellular trafficking of carriers and their cargoes as well as cellular
      uptake must be taken into consideration.

PMID- 25376865
TI  - Label-free in situ quantification of drug in living cells at micromolar levels
      using infrared spectroscopy.
AB  - Quantifying the rate and the amount of drug entering live cells is an essential
      part of the medicine development process. Infrared spectroscopy is a label-free,
      chemically selective tool for analyzing the composition of live cells in culture
      that has the potential to quantify, in situ, the amount of drug entering living
      cells in a nondestructive manner, although its sensitivity is currently limited.
      This paper is the first to demonstrate in situ quantification of the cancer drug,
      fluorouracil, in live cells at a therapeutically relevant concentration using
      Fourier transform infrared spectroscopy. To achieve the required improvement in
      detection and quantitation limits of the IR measurement, two strategies were
      exploited. First, a sampling method called multibounce attenuated total
      reflection was used to optimize the signal while second, a long pass filter in
      combination with a mercury cadmium telluride detector was used to reduce the
      instrument noise. Using these novel adaptations, it was possible to quantify 20
      MUM of fluorouracil in cell culture medium using a standard FTIR instrument,
      while it was possible to quantify and measure the flux of fluorouracil in situ in
      living cells treated with an 80 MUM drug. 

PMID- 25376867
TI  - Multifocal melanoma in situ of the penis treated with topical Imiquimod.

PMID- 25376866
TI  - Impact of the new risk stratification in the 2011 Japanese Society of Nephrology
      clinical guidelines for IgA nephropathy on incidence of early clinical remission
      with tonsillectomy plus steroid pulse therapy.
AB  - BACKGROUND: In 2011, the Japanese Society of Nephrology (JSN) published new
      clinical guidelines for IgA nephropathy (IgAN) with a new risk stratification
      based on clinical and histological severity. For classification, patients are
      divided into four groups (low, medium, high, and very high risk). However,
      differences in responsiveness to each treatment among different groups remain
      unclear. We evaluate the responsiveness of tonsillectomy plus steroid pulse (TSP)
      therapy using the new risk stratification. METHODS: We retrospectively reviewed
      111 IgAN patients with TSP therapy between January 2003 and January 2013. Study
      patients were divided into three groups [low- (n = 40), medium- (n = 43) and high
      /very high-risk group (n = 28)]. The primary outcome was clinical remission (CR).
      The observation period was 1 year following tonsillectomy. RESULTS: 57 out of 111
      patients (51.4 %) reached CR. The CR incidence was 70.0, 41.9 and 39.3 % (the low
      , the medium- and the high-/very high-risk group, respectively). The incidence of
      CR was significantly higher in the low-risk group (P = 0.013). In a multivariate
      logistic regression analysis, both the medium- and the high-/very high-risk group
      showed significantly lower incidence of inducing CR than the low-risk group
      [(odds ratio 0.324; 95 % confidence interval 0.106-0.939, P = 0.041) (odds ratio
      0.239; 95 % confidence interval 0.058-0.910, P = 0.040), respectively].
      CONCLUSIONS: The new risk stratification in the 2011 JSN clinical guidelines for
      IgAN had a positive impact on early CR of TSP therapy.

PMID- 25376868
TI  - Prognostic significance of lymphovascular invasion in node-negative gastric
      cancer.
AB  - BACKGROUND: The aim of this study was to investigate the prognostic value of
      lymphovascular invasion (LVI) in gastric cancer patients without lymph node
      metastasis. METHODS: A total of 699 patients with primary tumor pT1-3/pN0-1
      gastric adenocarcinoma who underwent curative resection from 2001 to 2010 were
      categorized into 3 groups: One-hundred and eleven patients with pN0/LVI(+), 475
      with pN0/LVI(-), and 103 with pN1. RESULTS: The tumors in patients with N0/LVI(+)
      had more aggressive clinicopathologic features than those in patients with
      N0/LVI(-). However, there was no significant difference in patient
      characteristics between patients with pN0/LVI(+) and those with pN1, except for
      histologic grade. There were no significant differences in the overall survival
      rate in patients with pN0/LVI(+) compared to those with pN0/LVI(-) or the pN1
      stage. However, the recurrence-free survival rate of the pN0/LVI(+) group was
      lower than that of the pN0/LVI(-) group (p < 0.001), while no significant
      difference was observed between the pN0/LVI(+) and the N1 groups (p = 0.216). In
      multivariate analysis, LVI was identified as a poor prognostic factor related to
      recurrence-free survival in node-negative gastric cancer patients. pT3 stage and
      less than D2 lymphadenectomy were poor prognostic factors affecting recurrence
      free survival, and less than D2 lymphadenectomy was an independent poor
      prognostic factor for overall survival in pN0/LVI(+) patients. CONCLUSIONS: LVI
      could be an indicator of biological aggressiveness and may be a reliable
      prognostic factor for node-negative gastric cancer. LVI should be considered in
      postoperative management of gastric cancer.

PMID- 25376870
TI  - Demonstration of the Pericallosal Artery at 11-13 Weeks of Gestation Using 3D
      Ultrasound.
AB  - OBJECTIVE: To assess the sonographic visualization of the pericallosal arteries
      in normal fetuses at 11-13 weeks of gestation using 3D ultrasound. METHODS: We
      prospectively enrolled women with a singleton pregnancy undergoing ultrasound at
      11-13 weeks of gestation. A 3D volume with high-definition power Doppler was
      acquired starting from the sagittal view of the fetal head and stored in the
      spatiotemporal image correlation mode. The images of the pericallosal arteries
      were assigned a score of 0 (no visualization), 1 (visualization of the origin) or
      2 (visualization of the whole course). A follow-up scan was performed in all
      cases at 20 weeks of gestation to assess the presence of the corpus callosum.
      RESULTS: 70 patients were included and the pericallosal arteries were
      sonographically detectable in all cases. Image scores of 1 and 2 were obtained in
      8 and 62 cases, respectively. The whole length of the vessel was between 3.5 and
      4.5 mm. The vast majority of those with a score of 2 were beyond 12 completed
      weeks of gestation. All fetuses showed a normal corpus callosum at midtrimester
      and no abnormal brain findings after birth. CONCLUSIONS: The pericallosal
      arteries are sonographically visible since the first trimester in 3D ultrasound
      scans of fetuses found to have a normal corpus callosum at follow-up.

PMID- 25376871
TI  - Selective and Scalable Synthesis of Trifluoromethanesulfenamides and Fluorinated
      Unsymmetrical Disulfides using a Shelf-Stable Electrophilic SCF3 Reagent.
AB  - The chemoselective trifluoromethylthiolation of nitrogen nucleophiles and thiols
      using N-(trifluoromethylthio)phthalimide under mild, metal-free conditions is
      described. A series of trifluoromethanesulfenamides and unsymmetrical disulfides
      is prepared from the corresponding aliphatic and aromatic amines and thiols in
      good yields. The reactions are operationally simple and tolerate a wide variety
      of functional groups. Trifluoromethanesulfenamides and disulfides belong to
      interesting classes of organic molecules which possess remarkable properties for
      medicinal and agrochemical applications.

PMID- 25376869
TI  - Community-based assessment of surgical symptoms in a low-income urban population.
AB  - BACKGROUND: The global burden of surgical disease has not been well quantified,
      but is potentially immense. Given the enormity of the problem and the relative
      paucity of data, definition and monitoring of surgical burden of disease is an
      essential step in confronting the problem. This study aimed to estimate the
      prevalence of non-acute surgical disease symptoms in a low-income population.
      METHODS: The survey was conducted as part of the Indus Hospital Community Cohort
      in Karachi, Pakistan. A systematic random sampling design was used to enroll 667
      households from March to August 2011. An unvalidated questionnaire intending to
      measure prevalence of surgical symptoms was administered to 780 participants.
      RESULTS: 761 participants completed the screening questionnaire, with 346 (45%)
      reporting one or more symptoms requiring surgical assessment (excluding those
      screened positive for symptoms of osteoarthritis), of which only 8.4% followed up
      on scheduled appointments at the referral hospital. A total of 126 past surgical
      procedures were recorded in 120 participants. CONCLUSION: There is a high
      prevalence of symptoms suggestive of surgical diseases in our urban catchment
      population with relatively convenient access to health facilities including a
      tertiary care hospital providing free of cost care. The perceived severity of
      symptoms, and a complex interaction of other factors, may play an important role
      in understanding health seeking behavior in our population. Developing a context
      specific validated tool to correctly identify surgical symptoms disease in the
      community with appropriate referral for early management is essential to identify
      and therefore reduce the burden of surgical diseases within the community. This
      must happen hand in hand with further studies to understand the barriers to
      seeking timely health care.

PMID- 25376872
TI  - Increased thyroid cancer incidence corresponds to increased use of thyroid
      ultrasound and fine-needle aspiration: a study of the Veterans Affairs health
      care system.
AB  - BACKGROUND: Thyroid cancer incidence has increased in the last several decades
      and may represent either a true increase in the number of cases or increased
      screening. The objective of this study was to examine thyroid cancer incidence
      and the use of thyroid ultrasound and fine-needle aspiration (FNA) screening in
      the Veterans Affairs (VA) health care system. The authors hypothesized that the
      incidence of thyroid cancer would correspond to increases in the use of these
      diagnostic modalities. METHODS: This was a multiyear, cross-sectional study using
      VA administrative data from 2000 to 2012. Joinpoint regression analysis was used
      to identify trends in thyroid cancer incidence and the use of thyroid ultrasound
      and FNA. RESULTS: An increase in thyroid cancer incidence occurred from 10.3 per
      100,000 individuals in 2000 to 21.5 per 100,000 individuals in 2012. The rate of
      thyroid ultrasound use increased from 125.6 per 100,000 individuals in 2001 to
      572.1 per 100,000 individuals in 2012, and the rate of thyroid FNA use increased
      from 7.0 per 100,000 individuals in 2000 to 46.2 per 100,000 individuals in 2012.
      A statistically significant increase in thyroid cancer incidence between 2000 and
      2008 (annual percent change [APC], 3.81; P < .05) was followed by a more
      pronounced increase between 2008 and 2012 (APC, 10.32; P < .05). A simultaneous
      increase in the use of thyroid ultrasound occurred between 2002 and 2012 (APC,
      15.48; P < .05) and the use of thyroid FNA between 2000 and 2012 (APC, 18.36; P <
      .05). CONCLUSIONS: Although the incidence of thyroid cancer doubled, a nearly 5
      fold increase in the use of thyroid ultrasound and a nearly 7-fold increase in
      the use of thyroid FNA occurred between 2000 and 2012. These findings suggest
      that the increase in thyroid cancer incidence may be related to increases in the
      use of thyroid ultrasound and FNA.

PMID- 25376873
TI  - Ecogenomics of Geminivirus from India and neighbor countries: An in silico
      analysis of recombination phenomenon.
AB  - Recombination is one of the keys factor in evolutionary processes, involved in
      shaping the architecture of genomes and consequent phenotype. Understanding the
      recombination phenomenon especially among viruses will help in disease
      management. The present study aimed for in-silico analysis of recombination
      phenomenon among Begomoviruses. Particularly emphasizing on viruses strains
      reported from India and neighboring countries. A total of 956 virus sequences
      have been used in this study. The Tomato yellow leaf curl China viruses, namely
      gi|29825986|; gi|283468151|; gi|190559151| and gi|61652782| were identified with
      the highest number of recombination event (1273). However, the Mung bean yellow
      mosaic India virus (gi|66351988|) was found to have 1170 recombination event. The
      phylogenic analysis among the highly recombinant sequences was carried to get an
      insight of the evolution among viral sequences in this class of plant viruses.
      The phylogenetic analysis revealed a pattern in diversity among these virus
      strains and a split tree analysis showed diversity in the range of 0.049128335 to
      10.269852. This in silico analysis may pave way for a greater understanding of
      recombination phenomenon in Ggeminiviruses and it might be helpful for strategic
      plant viral disease management.

PMID- 25376874
TI  - Quantifying uncertainty in the trophic magnification factor related to spatial
      movements of organisms in a food web.
AB  - Trophic magnification factors (TMFs) provide a method of assessing chemical
      biomagnification in food webs and are increasingly being used by policy makers to
      screen emerging chemicals. Recent reviews have encouraged the use of
      bioaccumulation models as screening tools for assessing TMFs for emerging
      chemicals of concern. The present study used a food web bioaccumulation model to
      estimate TMFs for polychlorinated biphenyls (PCBs) in a riverine system. The
      uncertainty associated with model predicted TMFs was evaluated against realistic
      ranges for model inputs (water and sediment PCB contamination) and variation in
      environmental, physiological, and ecological parameters included within the
      model. Finally, the model was used to explore interactions between spatial
      heterogeneity in water and sediment contaminant concentrations and theoretical
      movement profiles of different fish species included in the model. The model
      predictions of magnitude of TMFs conformed to empirical studies. There were
      differences in the relationship between the TMF and the octanol-water
      partitioning coefficient (KOW ) depending on the modeling approach used; a
      parabolic relationship was predicted under deterministic scenarios, whereas a
      linear TMF-KOW relationship was predicted when the model was run stochastically.
      Incorporating spatial movements by fish had a major influence on the magnitude
      and variation of TMFs. Under conditions where organisms are collected exclusively
      from clean locations in highly heterogeneous systems, the results showed bias
      toward higher TMF estimates, for example the TMF for PCB 153 increased from 2.7
      to 5.6 when fish movement was included. Small underestimations of TMFs were found
      where organisms were exclusively sampled in contaminated regions, although the
      model was found to be more robust to this sampling condition than the former for
      this system.

PMID- 25376875
TI  - Towards synthetic biological approaches to resource utilization on space
      missions.
AB  - This paper demonstrates the significant utility of deploying non-traditional
      biological techniques to harness available volatiles and waste resources on
      manned missions to explore the Moon and Mars. Compared with anticipated non
      biological approaches, it is determined that for 916 day Martian missions: 205
      days of high-quality methane and oxygen Mars bioproduction with Methanobacterium
      thermoautotrophicum can reduce the mass of a Martian fuel-manufacture plant by
      56%; 496 days of biomass generation with Arthrospira platensis and Arthrospira
      maxima on Mars can decrease the shipped wet-food mixed-menu mass for a Mars stay
      and a one-way voyage by 38%; 202 days of Mars polyhydroxybutyrate synthesis with
      Cupriavidus necator can lower the shipped mass to three-dimensional print a 120
      m(3) six-person habitat by 85% and a few days of acetaminophen production with
      engineered Synechocystis sp. PCC 6803 can completely replenish expired or
      irradiated stocks of the pharmaceutical, thereby providing independence from
      unmanned resupply spacecraft that take up to 210 days to arrive. Analogous
      outcomes are included for lunar missions. Because of the benign assumptions
      involved, the results provide a glimpse of the intriguing potential of 'space
      synthetic biology', and help focus related efforts for immediate, near-term
      impact. 

PMID- 25376876
TI  - Flexibility of bacterial flagella in external shear results in complex swimming
      trajectories.
AB  - Many bacteria use rotating helical flagella in swimming motility. In the search
      for food or migration towards a new habitat, bacteria occasionally unbundle their
      flagellar filaments and tumble, leading to an abrupt change in direction.
      Flexible flagella can also be easily deformed by external shear flow, leading to
      complex bacterial trajectories. Here, we examine the effects of flagella
      flexibility on the navigation of bacteria in two fundamental shear flows: planar
      shear and Poiseuille flow realized in long channels. On the basis of slender body
      elastodynamics and numerical analysis, we discovered a variety of non-trivial
      effects stemming from the interplay of self-propulsion, elasticity and shear
      induced flagellar bending. We show that in planar shear flow the bacteria execute
      periodic motion, whereas in Poiseuille flow, they migrate towards the centre of
      the channel or converge towards a limit cycle. We also find that even a small
      amount of random reorientation can induce a strong response of bacteria, leading
      to overall non-periodic trajectories. Our findings exemplify the sensitive role
      of flagellar flexibility and shed new light on the navigation of bacteria in
      complex shear flows. 

PMID- 25376877
TI  - Prevalence and risk factors for dysphagia: a USA community study.
AB  - BACKGROUND: Dysphagia is considered an alarm symptom but detailed population
      based data on dysphagia are lacking. We aimed to estimate in a representative USA
      Caucasian population, the prevalence of dysphagia and potential risk factors.
      METHODS: A modified version of the previously validated Bowel Disease
      Questionnaire was mailed to a population-based cohort (n = 7640) of Olmsted
      County, MN. Dysphagia was measured by one validated question 'In the last year,
      how often have you had difficulty swallowing (a feeling that food sticks in your
      throat or chest)?' The medical records were reviewed for organic causes of
      dysphagia. The associations of reported frequency of dysphagia with potential
      risk factors were assessed using logistic regression models. KEY RESULTS: The sex
      specific, age-adjusted (US White 2000) prevalence for dysphagia experienced at
      least weekly was 3.0% (95% CI: 2.2, 3.7) in females and 3.0% (95% CI: 2.0, 4.0)
      in males. Those with frequent heartburn (OR = 5.9 [4.0, 8.6]) and acid
      regurgitation (OR = 10.6 [6.8, 16.6]) were significantly more likely to report
      frequent dysphagia. Proton pump inhibitor (PPI) use was significantly associated
      with frequent (3.1, 95% CI 2.2, 4.4) and infrequent dysphagia (1.5, 955 CI 1.3,
      1.8). Gastro-esophageal reflux disease (GERD) was the most common diagnosis in
      those reporting dysphagia on the medical record; other organic explanations were
      rare and only found in the frequent dysphagia group. CONCLUSIONS & INFERENCES:
      Frequent dysphagia is not rare in the community (3%), occurs in both women and
      men across all adult age groups, and is most likely to indicate underlying GERD.

PMID- 25376878
TI  - Patterns of genetic variation and the role of selection in HTR1A and HTR1B in
      macaques (Macaca).
AB  - BACKGROUND: Research has increasingly highlighted the role of serotonin in
      behavior. However, few researchers have examined serotonin in an evolutionary
      context, although such research could provide insight into the evolution of
      important behaviors. The genus Macaca represents a useful model to address this,
      as this genus shows a wide range of behavioral variation. In addition, many
      genetic features of the macaque serotonin system are similar to those of humans,
      and as common models in biomedical research, knowledge of the genetic variation
      and evolution of serotonin functioning in macaques are particularly relevant for
      studies of human evolution. Here, we examine the role of selection in the macaque
      serotonin system by comparing patterns of genetic variation for two genes that
      code for two types of serotonin receptors - HTR1A and HTR1B - across five species
      of macaques. RESULTS: The pattern of variation is significantly different for
      HTR1A compared to HTR1B. Specifically, there is an increase in between-species
      variation compared to within-species variation for HTR1A. Phylogenetic analyses
      indicate that portions of HTR1A show an elevated level of nonsynonymous
      substitutions. Together these analyses are indicative of positive selection
      acting on HTR1A, but not HTR1B. Furthermore, the haplotype network for HTR1A is
      inconsistent with the species tree, potentially due to both deep coalescence and
      selection. CONCLUSIONS: The results of this study indicate distinct evolutionary
      histories for HTR1A and HTR1B, with HTR1A showing evidence of selection and a
      high level of divergence among species, a factor which may have an impact on
      biomedical research that uses these species as models. The wide genetic variation
      of HTR1A may also explain some of the species differences in behavior, although
      further studies on the phenotypic effect of the sequenced polymorphisms are
      needed to confirm this.

PMID- 25376880
TI  - Controlled deposition of highly ordered soluble acene thin films: effect of
      morphology and crystal orientation on transistor performance.
AB  - Controlling the morphology of soluble small molecule organic semiconductors is
      crucial for the application of such materials in electronic devices. Using a
      simple dip-coating process we systematically vary the film drying speed to
      produce a range of morphologies, including oriented needle-like crystals.
      Structural characterization as well as electrical transistor measurements show
      that intermediate drying velocities produce the most uniformly aligned films. 

PMID- 25376881
TI  - Sperm Proteome: What Is on the Horizon?
AB  - As the mammalian spermatozoa transcends from the testis to the end of the
      epididymal tubule, the functionally incompetent spermatozoa acquires its
      fertilizing capability. Molecular changes in the spermatozoa at the
      posttesticular level concern qualitative and quantitative modifications of
      proteins along with their sugar moieties and membranous lipids mostly associated
      with motility, egg binding, and penetration processes. Proteomic studies have
      identified numerous sperm-specific proteins, and recent reports have provided a
      further understanding of their function with respect to male fertility. High
      throughput techniques such as mass spectrometry have shown drastic potential for
      the identification and study of sperm proteins. In fact, compelling evidence has
      provided that proteins are critically important in cellular remodeling event and
      that aberrant expression is associated with pronounced defects in sperm function.
      This review highlights the posttesticular functional transformation in the
      epididymis and female reproductive tract with due emphasis on proteomics. 

PMID- 25376879
TI  - Type-1 pericytes accumulate after tissue injury and produce collagen in an organ
      dependent manner.
AB  - INTRODUCTION: Fibrosis, or scar formation, is a pathological condition
      characterized by excessive production and accumulation of collagen, loss of
      tissue architecture, and organ failure in response to uncontrolled wound healing.
      Several cellular populations have been implicated, including bone marrow-derived
      circulating fibrocytes, endothelial cells, resident fibroblasts, epithelial
      cells, and recently, perivascular cells called pericytes. We previously
      demonstrated pericyte functional heterogeneity in skeletal muscle. Whether
      pericyte subtypes are present in other tissues and whether a specific pericyte
      subset contributes to organ fibrosis are unknown. METHODS: Here, we report the
      presence of two pericyte subtypes, type-1 (Nestin-GFP-/NG2-DsRed+) and type-2
      (Nestin-GFP+/NG2-DsRed+), surrounding blood vessels in lungs, kidneys, heart,
      spinal cord, and brain. Using Nestin-GFP/NG2-DsRed transgenic mice, we induced
      pulmonary, renal, cardiac, spinal cord, and cortical injuries to investigate the
      contributions of pericyte subtypes to fibrous tissue formation in vivo. RESULTS:
      A fraction of the lung's collagen-producing cells corresponds to type-1 pericytes
      and kidney and heart pericytes do not produce collagen in pathological fibrosis.
      Note that type-1, but not type-2, pericytes increase and accumulate near the
      fibrotic tissue in all organs analyzed. Surprisingly, after CNS injury, type-1
      pericytes differ from scar-forming PDGFRbeta + cells. CONCLUSIONS: Pericyte
      subpopulations respond differentially to tissue injury, and the production of
      collagen by type-1 pericytes is organ-dependent. Characterization of the
      mechanisms underlying scar formation generates cellular targets for future anti
      fibrotic therapeutics.

PMID- 25376882
TI  - Isolation and characterization of ex vivo expanded mesenchymal stem cells
      obtained from a surgical patient.
AB  - The aim of the present study was to investigate the morphological characteristics
      and pluripotent differentiation potential of human bone marrow mesenchymal stem
      cells (hBMMSCs) in vitro and in vivo. Bone marrow cells were isolated from a rib
      fragment of an adult surgical patient, hBMMSCs were isolated based on plastic
      adherence and expanded ex vivo and phenotyping was performed. Pluripotent
      differentiation assays for adipogenesis, myogenesis and osteogenesis were
      conducted. Hematopoietic reconstruction of sublethally irradiated nude mice was
      performed by infusion of hBMMSCs. The gene expression profiles of early and late
      hBMMSCs were examined. The rate of CD31-positive cells was 31.1% in passage (P)4
      hBMMSCs and 18.6% in P10 hBMMSCs. CD105 and CD106 were expressed in 99 and 95% of
      P25 hBMMSCs, respectively. Lipid droplets appeared at day 18 post induction. For
      osteogenesis, palpable masses were grossly observed from day 35 post inoculation
      of hBMMSCs. Hematoxylin and eosin staining further revealed chondrocytes and bone
      tissues. For myogenesis, at day six post subcutaneous inoculation, hBMMSCs
      differentiated into myocytes and were positive for myoglobin and MyoD1. In
      irradiated nude mice reconstituted by hBMMSCs, the white blood cell count briefly
      decreased following irradiation; however, it gradually recovered. In the
      irradiated nude mice reconstituted with hBMMSCs, CD45- and CD34-positive cells
      were detected 72 h post induction. Gene microarray analysis of P7 and P57 hBMMSCs
      demonstrated that 20 genes were upregulated >2 fold and 40 genes were
      downregulated >2 fold in P57 hBMMSCs. In conclusion, the isolated HBMMSCs
      possessed pluripotent differentiation potential and it was feasible and safe to
      use hBMMSCs within 30 passages.

PMID- 25376883
TI  - Changes in communication of Deaf people with dementia: A thematic interview with
      a close family member.
AB  - BACKGROUND AND AIM: Learning about changes in communication of Deaf with dementia
      (DWD) is important in order to improve services and support DWD and their
      families. We explored family members' views on the changes in communication DWD
      have and the ways communication was adapted due to progression of dementia.
      METHODS: A qualitative content analysis of thematic interviews that were
      conducted with eight close family members of DWD. RESULTS: With decreasing
      vocabulary and increasing sign-finding difficulties, conversations became poorer,
      and DWD tended to diverge from the topic. Nonverbal communication became more
      important as the verbal communication abilities of DWD deteriorated, and the
      adult children took a more active role by taking initiative and guiding
      conversations. CONCLUSION: DWD seem to go through similar changes in
      communication as hearing people with dementia. Adult children of DWD need to get
      used to interpreting and assisting their parent's communication through different
      phases of dementia.

PMID- 25376885
TI  - Factors associated with risk behavior in travelers to tropical and subtropical
      regions.
AB  - BACKGROUND: Recent decades have seen a rise in population movements and,
      therefore, the spread of tropical diseases and changes in the epidemiology of
      global disease patterns. Only 50% of travelers to tropical areas receive pre
      travel advice and most of them present risk behaviors for acquiring infections.
      The aim of this study was to describe the clinical and epidemiological
      characteristics of travelers and identify factors associated with risk behaviors.
      METHODS: We made a retrospective, descriptive and analytical study of 772
      travelers consulting a tropical medicine clinic in Barcelona in 2010. Data on
      demographic and clinical variables, travel characteristics and risk behaviors
      were collected. RESULTS: Among all travelers studied, 65.8% (466/708) received
      pre-travel advice and 30.7% (209/680) took malaria prophylaxis. At least one risk
      behavior was reported by 82.6% (587/711) of travelers. People traveling for 1-6
      months had a 3-fold higher likelihood of experiencing risk behaviors than people
      traveling for <1 month (95% CI 1.54-5.81, p=0.001), and those traveling for >6
      months had a 13-fold higher likelihood (95% CI 3.11-56.14, p<0.001) compared with
      the same group. Increasing age was associated with presenting less risk
      behaviors. CONCLUSIONS: Younger travelers and those making longer trips have a
      higher number of risk behaviors. Strategies emphasizing advice on risk behavior
      should focus on these groups.

PMID- 25376887
TI  - Knowledge and tools to enhance resilience of beef grazing systems for sustainable
      animal protein production.
AB  - Ruminant livestock provides meat and dairy products that sustain health and
      livelihood for much of the world's population. Grazing lands that support
      ruminant livestock provide numerous ecosystem services, including provision of
      food, water, and genetic resources; climate and water regulation; support of soil
      formation; nutrient cycling; and cultural services. In the U.S. southern Great
      Plains, beef production on pastures, rangelands, and hay is a major economic
      activity. The region's climate is characterized by extremes of heat and cold and
      extremes of drought and flooding. Grazing lands occupy a large portion of the
      region's land, significantly affecting carbon, nitrogen, and water budgets. To
      understand vulnerabilities and enhance resilience of beef production, a multi
      institutional Coordinated Agricultural Project (CAP), the "grazing CAP," was
      established. Integrative research and extension spanning biophysical,
      socioeconomic, and agricultural disciplines address management effects on
      productivity and environmental footprints of production systems. Knowledge and
      tools being developed will allow farmers and ranchers to evaluate risks and
      increase resilience to dynamic conditions. The knowledge and tools developed will
      also have relevance to grazing lands in semiarid and subhumid regions of the
      world. 

PMID- 25376884
TI  - The effects of progressive resistance training combined with a whey-protein drink
      and vitamin D supplementation on glycaemic control, body composition and
      cardiometabolic risk factors in older adults with type 2 diabetes: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: While physical activity, energy restriction and weight loss are the
      cornerstone of type 2 diabetes management, less emphasis is placed on optimizing
      skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue
      and the predominant reservoir for glucose disposal, there is a need to develop
      safe and effective evidence-based, lifestyle management strategies that optimize
      muscle mass as well as improve glycaemic control and cardiometabolic risk factors
      in people with this disease, particularly older adults who experience accelerated
      muscle loss. METHODS/DESIGN: Using a two-arm randomized controlled trial, this 6
      month study builds upon the community-based progressive resistance training (PRT)
      programme Lift for Life(r) to evaluate whether ingestion of a whey-protein drink
      combined with vitamin D supplementation can enhance the effects of PRT on
      glycaemic control, body composition and cardiometabolic health in older adults
      with type 2 diabetes. Approximately 200 adults aged 50 to 75 years with type 2
      diabetes, treated with either diet alone or oral hypoglycaemic agents (not
      insulin), will be recruited. All participants will be asked to participate in a
      structured, supervised PRT programme based on the Lift for Life(r) programme
      structure, and randomly allocated to receive a whey-protein drink (20 g daily of
      whey-protein plus 20 g after each PRT session) plus vitamin D supplements (2000
      IU/day), or no additional powder and supplements. The primary outcome measures to
      be collected at baseline, 3 and 6 months will be glycated haemoglobin (HbA1c) and
      insulin sensitivity (homeostatic model assessment). Secondary outcomes will
      include changes in: muscle mass, size and intramuscular fat; fat mass; muscle
      strength and function; blood pressure; levels of lipids, adipokines and
      inflammatory markers, serum insulin-like growth factor-1 and 25-hydroxyvitamin D;
      renal function; diabetes medication; health-related quality of life, and
      cognitive function. DISCUSSION: The findings from this study will provide new
      evidence on whether increased dietary protein achieved through the ingestion of a
      whey-protein drink combined with vitamin D supplementation can enhance the
      effects of PRT on glycaemic control, muscle mass and size, and cardiometabolic
      risk factors in older adults with type 2 diabetes. TRIAL REGISTRATION: Australian
      New Zealand Clinical Trials ACTRN12613000592741.

PMID- 25376888
TI  - Land-based production of animal protein: impacts, efficiency, and sustainability.
AB  - Land-based production of high-quality protein by livestock and poultry plays an
      important role in improving human nutrition, growth, and health, as well as
      economical and social developments worldwide. With exponential growth of the
      global population and marked rises in meat consumption per capita, demands for
      animal-source protein are expected to increase by 72% between 2013 and 2050. This
      raises concerns about the sustainability and environmental impacts of animal
      agriculture. An attractive solution to meeting the increasing needs for animal
      products and mitigating undesired effects of agricultural practices is to enhance
      the efficiency of animal growth, reproduction, and lactation. Breeding techniques
      may help achieve this goal, but have only met with limited success. A promising,
      mechanism-based approach is to optimize the proportion and amounts of amino acids
      in diets for maximizing whole-body protein synthesis and feed efficiency.
      Improvements in farm animal productivity will not only decrease the contamination
      of soils, groundwater, and air by excessive manure, but will also help sustain
      animal agriculture to produce high-quality protein for the expanding population
      in the face of diminishing resources. 

PMID- 25376886
TI  - Probing mechanoregulation of neuronal differentiation by plasma lithography
      patterned elastomeric substrates.
AB  - Cells sense and interpret mechanical cues, including cell-cell and cell-substrate
      interactions, in the microenvironment to collectively regulate various
      physiological functions. Understanding the influences of these mechanical factors
      on cell behavior is critical for fundamental cell biology and for the development
      of novel strategies in regenerative medicine. Here, we demonstrate plasma
      lithography patterning on elastomeric substrates for elucidating the influences
      of mechanical cues on neuronal differentiation and neuritogenesis. The
      neuroblastoma cells form neuronal spheres on plasma-treated regions, which
      geometrically confine the cells over two weeks. The elastic modulus of the
      elastomer is controlled simultaneously by the crosslinker concentration. The cell
      substrate mechanical interactions are also investigated by controlling the size
      of neuronal spheres with different cell seeding densities. These physical cues
      are shown to modulate with the formation of focal adhesions, neurite outgrowth,
      and the morphology of neuroblastoma. By systematic adjustment of these cues,
      along with computational biomechanical analysis, we demonstrate the interrelated
      mechanoregulatory effects of substrate elasticity and cell size. Taken together,
      our results reveal that the neuronal differentiation and neuritogenesis of
      neuroblastoma cells are collectively regulated via the cell-substrate mechanical
      interactions. 

PMID- 25376889
TI  - An alternative animal protein source: cultured beef.
AB  - Alternative sources of animal proteins are needed that can be produced
      efficiently, thereby providing food security with diminished ecological burden.
      It is feasible to culture beef from bovine skeletal muscle stem cells, but the
      technology is still under development. The aim is to create a beef mimic with
      equivalent taste, texture, and appearance and with the same nutritional value as
      livestock-produced beef. More specifically, there is a need for optimization of
      protein content and fat content. In addition, scalability of production requires
      modification of current small-scale bioreactors to the largest possible scale.
      The necessary steps and current progress suggest that this aim is achievable, but
      formal evidence is still required. Similarly, we can be optimistic about consumer
      acceptance based on initial data, but detailed studies are needed to gain more
      insight into potential psychological obstacles that could lead to rejection.
      These challenges are formidable but likely surmountable. The severity of upcoming
      food-security threats warrants serious research and development efforts to
      address the challenges that come with bringing cultured beef to the market. 

PMID- 25376890
TI  - Increased pain sensitivity in chronic pain subjects on opioid therapy: a cross
      sectional study using quantitative sensory testing.
AB  - OBJECTIVE: The aim of this study was to compare the sensitivity to experimental
      pain of chronic pain patients on opioid therapy vs chronic pain patients on non
      opioid therapy and healthy subjects by quantitative sensory testing (QST).
      SETTING: There is a growing body of evidence demonstrating that chronic use of
      opioid drugs may alter pain sensitivity. Identifying the characteristic changes
      in thermal pain sensitivity in chronic opioid users will be helpful in diagnosing
      pain sensitivity alterations associated with chronic opioid use. METHODS:
      Utilizing an office-based QST technique, we examined thermal pain threshold,
      tolerance, and temporal summation in 172 chronic pain subjects receiving opioid
      therapy, 121 chronic pain subjects receiving non-opioid therapy, and 129 healthy
      subjects. RESULTS: In chronic pain subjects receiving opioid therapy, there were
      detectable differences in QST characteristics compared with both chronic pain
      subjects receiving non-opioid therapy and healthy subjects. Specifically, in
      chronic pain subjects receiving opioid therapy, 1) sensitivity to heat pain was
      increased; threshold to heat pain was significantly lower; 2) tolerance to supra
      threshold heat pain was significantly decreased; and 3) temporal pain summation
      was exacerbated, as compared with chronic pain subjects receiving non-opioid
      therapy. In a subgroup of chronic pain subjects receiving opioid therapy with
      increased heat pain sensitivity, their average opioid medication dosage was
      significantly higher than those who had an above-average heat pain threshold.
      Moreover, a subset of chronic pain subjects on opioid therapy exhibited a
      significant decrease in diffuse noxious inhibitory control (DNIC) compared with
      chronic pain subjects on non-opioid therapy. CONCLUSION: These findings suggest
      that a subset of QST parameters can reflect opioid-associated thermal pain
      sensitivity alteration, including decreased heat pain threshold, decreased cold
      and heat pain tolerance, diminished DNIC, and/or exacerbated temporal summation.

PMID- 25376892
TI  - Metal-free sigma-bond metathesis in 1,3,2-diazaphospholene-catalyzed
      hydroboration of carbonyl compounds.
AB  - The first metal-free catalytic hydroboration of carbonyl derivatives has been
      developed in which a catalytic amount of 1,3,2-diazaphospholene effectively
      promotes a hydroboration reaction of aliphatic and aromatic aldehydes and
      ketones. The reaction mechanism involves the cleavage of both the P?O bond of the
      alkoxyphosphine intermediate and the B?H bond of pinacolborane as well as the
      formation of P?H and B?O bonds. Thus, the reaction proceeds through a non-metal
      sigma-bond metathesis. Kinetic and computational studies suggest that the sigma
      bond metathesis occurred in a stepwise but nearly concerted manner. 

PMID- 25376894
TI  - [Anaphylactic reaction after peanut intake in a patient with birch pollen
      allergy].

PMID- 25376895
TI  - [Congenital sensorineural deafness with microtia and Michel aplasia].

PMID- 25376893
TI  - MR imaging probes: design and applications.
AB  - This perspective outlines strategies towards the development of MR imaging probes
      that our lab has explored over the last 15 years. Namely, we discuss methods to
      enhance the signal generating capacity of MR probes and how to achieve tissue
      specificity through protein targeting or probe activation within the tissue
      microenvironment. 

PMID- 25376896
TI  - [Osteoclastic giant cell tumor of the vocal cord].

PMID- 25376897
TI  - Histologic findings following use of hydrophilic polymer with potassium ferrate
      for hemostasis.
AB  - Hydrophilic polymer with potassium salt is a hemostatic agent marketed for use by
      healthcare professionals and as an over-the-counter product available to
      healthcare consumers. In particular, dermatologic surgeons may use hydrophilic
      polymer for hemostasis in wounds left to heal by secondary intention. Foreign
      body reaction to hydrophilic polymer was recently reported. The microscopic
      findings in four additional patients treated with hydrophilic polymer are
      presented. The wounds of three patients were treated with hydrophilic polymer
      following a dermatologic surgical procedure while one patient used over-the
      counter hydrophilic polymer on an abrasion. Three patients developed a foreign
      body reaction. Histopathologic examination revealed angulated fragments of deep
      purple material representing hydrophilic polymer admixed with round orange-red
      bodies and yellow-brown granules representing potassium ferrate. The components
      were found both free in the dermis and within multinucleated giant cells.
      Hydrophilic polymer must be differentiated from other materials observed in re
      excision specimens, including ferric subsulfate, aluminum chloride and
      Gelfoam((r)) (Pharmacia and Upjohn Co., New York, NY, USA).

PMID- 25376900
TI  - In situ detection and identification of hesperidin crystals in satsuma mandarin
      (Citrus unshiu) peel cells.
AB  - INTRODUCTION: Hesperidin, a flavonoid known to have important pharmacological
      effects, accumulates particularly in the peels of satsuma mandarin (Citrus
      unshiu). Although histochemical studies have suggested that hesperidin forms
      crystals in some tissues of the Rutaceae and Umbelliferae, there has been no
      rigorous in situ detection or identification of hesperidin crystals in C. unshiu.
      OBJECTIVE: To characterise the chemical component of the crystals found in C.
      unshiu peels using Raman microscopy. METHODS: Sections of C. unshiu peels were
      made. The distribution and morphology of crystals in the sections were analysed
      microscopically. Raman microscopy was used to detect hesperidin in the sections
      directly. RESULTS: The crystals were more abundant in immature peel and were
      observed particularly in areas surrounding vascular bundles, around the border
      between the flavedo and albedo layers and just below the epidermal cells. In the
      morphological analysis by scanning electron microscopy, needle-shaped crystals
      aggregated and formed clusters of spherical crystals. Spectra obtained by Raman
      microscopy of the crystals in the peel sections were consistent with those of the
      hesperidin standard. CONCLUSION: This study showed the detailed distribution of
      crystals in C. unshiu peels and their main component was identified using Raman
      microscopy to be hesperidin for the first time.

PMID- 25376898
TI  - Microenvironmental acidosis in carcinogenesis and metastases: new strategies in
      prevention and therapy.
AB  - Much effort is currently devoted to developing patient-specific cancer therapy
      based on molecular characterization of tumors. In particular, this approach seeks
      to identify driver mutations that can be blocked through small molecular
      inhibitors. However, this approach is limited by extensive intratumoral genetic
      heterogeneity, and, not surprisingly, even dramatic initial responses are
      typically of limited duration as resistant tumor clones rapidly emerge and
      proliferate. We propose an alternative approach based on observations that while
      tumor evolution produces genetic divergence, it is also associated with striking
      phenotypic convergence that loosely correspond to the well-known cancer
      "hallmarks". These convergent properties can be described as driver phenotypes
      and may be more consistently and robustly expressed than genetic targets. To this
      purpose, it is necessary to identify strategies that are critical for cancer
      progression and metastases, and it is likely that these driver phenotypes will be
      closely related to cancer "hallmarks". It appears that an antiacidic approach, by
      targetting a driver phenotype in tumors, may be thought as a future strategy
      against tumors in either preventing the occurrence of cancer or treating tumor
      patients with multiple aims, including the improvement of efficacy of existing
      therapies, possibly reducing their systemic side effects, and controlling tumor
      growth, progression, and metastasis. This may be achieved with existing molecules
      such as proton pump inhibitors (PPIs) and buffers such as sodium bicarbonate,
      citrate, or TRIS. 

PMID- 25376899
TI  - Mineralocorticoid-induced sodium appetite and renal salt retention: evidence for
      common signaling and effector mechanisms.
AB  - An increase in renal sodium chloride (salt) retention and an increase in sodium
      appetite are the body's responses to salt restriction or depletion in order to
      restore salt balance. Renal salt retention and increased sodium appetite can also
      be maladaptive and sustain the pathophysiology in conditions like salt-sensitive
      hypertension and chronic heart failure. Here we review the central role of the
      mineralocorticoid aldosterone in both the increase in renal salt reabsorption and
      sodium appetite. We discuss the working hypothesis that aldosterone activates
      similar signaling and effector mechanisms in the kidney and brain, including the
      mineralocorticoid receptor, the serum- and glucocorticoid-induced kinase SGK1,
      the ubiquitin ligase NEDD4-2, and the epithelial sodium channel ENaC. The latter
      also mediates the gustatory salt sensing in the tongue, which is required for the
      manifestation of increased salt intake. Effects of aldosterone on both the brain
      and kidney synergize with the effects of angiotensin II. Thus, mineralocorticoids
      appear to induce similar molecular pathways in the kidney, brain, and possibly
      tongue, which could provide opportunities for more effective therapeutic
      interventions. Inhibition of renal salt reabsorption is compensated by
      stimulation of salt appetite and vice versa; targeting both mechanisms should be
      more effective. Inhibiting the arousal to consume salty food may improve a
      patient's compliance to reducing salt intake. While a better understanding of the
      molecular mechanisms is needed and will provide new therapeutic options, current
      pharmacological interventions that target both salt retention and sodium appetite
      include mineralocorticoid receptor antagonists and potentially inhibitors of
      angiotensin II and ENaC.

PMID- 25376902
TI  - Sustained virological response to antiviral therapy improves survival rate in
      patients with recurrent hepatitis C virus infection after liver transplantation.
AB  - AIM: Previous European and North American studies analyzed the relationship
      between survival rate and sustained virological response (SVR) to interferon
      (IFN) therapy in patients with recurrent hepatitis C viral (HCV) infection after
      liver transplantation (LT). The present study was designed to define the same
      relationship in Japanese patients who had undergone LT. METHODS: Forty-seven
      patients (genotype 1, 40; genotype 2, 7) with recurrent HCV after LT were treated
      with pegylated interferon (PEG IFN) or IFN/ribavirin (RBV). In possible, within 3
      months after LT, patients started treatment with PEG IFN-alpha-2b or IFN-alpha-2b
      s.c. once weekly combined with RBV (200 mg/day). RESULTS: The SVR rate was 51%
      (24/47) for all patients, 42.5% (17/40) for genotype 1 and 100% (7/7) for
      genotype 2. The median follow-up period was 71 months (range, 24-152). The
      survival rate of 24 patients who achieved SVR was 95% at 5 years and 92% at 10
      years. These rates were significantly better than those of 23 patients who did
      not achieve SVR (82% at 5 years, 58% at 10 years) (P = 0.027). Two patients of
      the SVR group died during follow up (due to hepatocellular carcinoma in one and
      chronic rejection in one), while six non-SVR patients died during the same period
      (three died due to liver failure by recurrent HCV). CONCLUSION: SVR following IFN
      therapy contributes to improvement of survival rate in patients with recurrent
      post-LT HCV infection.

PMID- 25376901
TI  - Genetic markers associated with plasma protein C level in African Americans: the
      atherosclerosis risk in communities (ARIC) study.
AB  - Protein C is an endogenous anticoagulant protein with anti-inflammatory
      properties. Single-nucleotide polymorphisms (SNPs) affect the levels of
      circulating protein C in European Americans. We performed a genome-wide
      association (GWA) scan of plasma protein C concentration with approximately 2.5
      million SNPs in 2,701 African Americans in the Atherosclerosis Risk in
      Communities Study. Seventy-nine SNPs from the 20q11 and 2q14 regions reached the
      genome-wide significance threshold of 5 * 10(-8) . A missense variant rs867186 in
      the PROCR gene at 20q11 is known to affect protein C levels in individuals of
      European descent and showed the strongest signal (P = 9.84 * 10(-65) ) in African
      Americans. The minor allele of this SNP was associated with higher protein C
      levels (beta = 0.49 MUg/ml; 10% variance explained). In the 2q14 region, the top
      SNPs were near or within the PROC gene: rs7580658 (beta = 0.15 MUg/ml; 2%
      variance explained, P = 1.7 * 10(-12) ) and rs1799808 (beta = 0.15 MUg/ml; 2%
      variance explained, P = 2.03 * 10(-12) ). These two SNPs were in strong linkage
      disequilibrium (LD) with another SNP rs1158867 that resides in a biochemically
      functional site and in weak to strong LD with the top PROC variants previously
      reported in individuals of European descent. In addition, two variants outside
      the PROC region were significantly and independently associated with protein C
      levels: rs4321325 in CYP27C1 and rs13419716 in MYO7B. In summary, this first GWA
      study for plasma protein C levels in African Americans confirms the associations
      of SNPs in the PROC and PROCR regions with circulating levels of protein C across
      ethnic populations and identifies new candidates for protein C regulation.

PMID- 25376903
TI  - Progesterone and allopregnanolone improves stroke outcome in male mice via
      distinct mechanisms but neither promotes neurogenesis.
AB  - Based on the outcome of a number of experimental studies, progesterone (PROG)
      holds promise as a new therapy for stroke. To understand more about the
      mechanisms involved, we administered PROG (or the major metabolite,
      allopregnanolone, ALLO), intra-peritoneally, for a period of 24 h after transient
      middle cerebral artery occlusion to male mice variably expressing intracellular
      progesterone receptors (iPR) A/B. Effects on infarct volume and neurogenesis were
      then assessed up to 1 month later. Predictably, infarct volume in wild-type mice
      receiving either drug was significantly smaller. However, mice heterozygous for
      iPRs A/B showed protection by ALLO but not by PROG. There was robust
      amplification of cell division in the wall of the lateral ventricle on the
      injured side of the brain, these cells migrated into the striatum and lateral
      cortex, and a significant number survived for at least 3 weeks. However, very few
      doublecortin-positive cells emerged from the subventricular zone and subsequent
      expression of NeuN in these newborn neurons was extremely rare. Neither PROG nor
      ALLO amplified the rate of neurogenesis, suggesting that the long-term benefits
      of acute drug administration results from tissue preservation. Male mice derive
      long-lasting benefit from progesterone and allopregnanolone after ischemic
      stroke. In mice heterozygous for iPRs, only allopregnanolone proved effective,
      suggesting distinct mechanisms. Abundant newborn cells were found in the wall of
      the lateral ventricle on the injured side (many doublecortin-positive), some
      migrated into the striatum and lateral cortex, but very few survived as mature
      neurons. Neurosteroid administration did not amplify this process. 

PMID- 25376905
TI  - McbR/YncC: implications for the mechanism of ligand and DNA binding by a
      bacterial GntR transcriptional regulator involved in biofilm formation.
AB  - MqsR-controlled colanic acid and biofilm regulator (McbR, also known as YncC) is
      the protein product of a highly induced gene in early Escherichia coli biofilm
      development and has been regarded as an attractive target for blocking biofilm
      formation. This protein acts as a repressor for genes involved in
      exopolysaccharide production and an activator for genes involved in stress
      response. To better understand the role of McbR in governing the switch from
      exponential growth to the biofilm state, we determined the crystal structure of
      McbR to 2.1 A. The structure reveals McbR to be a member of the FadR C-terminal
      domain (FCD) family of the GntR superfamily of transcriptional regulators (this
      family was named after the first identified member, GntR, a transcriptional
      repressor of the gluconate operon of Bacillus subtilis). Previous to this study,
      only six of the predicted 2800 members of this family had been structurally
      characterized. Here, we identify the residues that constitute the McbR effector
      and DNA binding sites. In addition, comparison of McbR with other members of the
      FCD domain family shows that this family of proteins adopts highly distinct
      oligomerization interfaces, which has implications for DNA binding and
      regulation. 

PMID- 25376907
TI  - DOWNY MILDEW RESISTANT 6 and DMR6-LIKE OXYGENASE 1 are partially redundant but
      distinct suppressors of immunity in Arabidopsis.
AB  - Arabidopsis downy mildew resistant 6 (dmr6) mutants have lost their
      susceptibility to the downy mildew Hyaloperonospora arabidopsidis. Here we show
      that dmr6 is also resistant to the bacterium Pseudomonas syringae and the
      oomycete Phytophthora capsici. Resistance is accompanied by enhanced defense gene
      expression and elevated salicylic acid levels. The suppressive effect of the DMR6
      oxygenase was confirmed in transgenic Arabidopsis lines overexpressing DMR6 that
      show enhanced susceptibility to H. arabidopsidis, P. capsici, and P. syringae.
      Phylogenetic analysis of the superfamily of 2-oxoglutarate Fe(II)-dependent
      oxygenases revealed a subgroup of DMR6-LIKE OXYGENASEs (DLOs). Within
      Arabidopsis, DMR6 is most closely related to DLO1 and DLO2. Overexpression of
      DLO1 and DLO2 in the dmr6 mutant restored the susceptibility to downy mildew
      indicating that DLOs negatively affect defense, similar to DMR6. DLO1, but not
      DLO2, is co-expressed with DMR6, showing strong activation during pathogen attack
      and following salicylic acid treatment. DMR6 and DLO1 differ in their spatial
      expression pattern in downy mildew-infected Arabidopsis leaves; DMR6 is mostly
      expressed in cells that are in contact with hyphae and haustoria of H.
      arabidopsidis, while DLO1 is expressed mainly in the vascular tissues near
      infection sites. Strikingly, the dmr6-3_dlo1 double mutant, that is completely
      resistant to H. arabidopsidis, showed a strong growth reduction that was
      associated with high levels of salicylic acid. We conclude that DMR6 and DLO1
      redundantly suppress plant immunity, but also have distinct activities based on
      their differential localization of expression.

PMID- 25376904
TI  - Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in
      hypertrophic cardiomyocytes.
AB  - BACKGROUND: Cardiac hypertrophy is characterized by alterations in both cardiac
      bioenergetics and insulin sensitivity. Insulin promotes glucose uptake by
      cardiomyocytes and its use as a substrate for glycolysis and mitochondrial
      oxidation in order to maintain the high cardiac energy demands. Insulin
      stimulates Ca(2+) release from the endoplasmic reticulum, however, how this
      translates to changes in mitochondrial metabolism in either healthy or
      hypertrophic cardiomyocytes is not fully understood. RESULTS: In the present
      study we investigated insulin-dependent mitochondrial Ca(2+) signaling in normal
      and norepinephrine or insulin like growth factor-1-induced hypertrophic
      cardiomyocytes. Using mitochondrion-selective Ca(2+)-fluorescent probes we showed
      that insulin increases mitochondrial Ca(2+) levels. This signal was inhibited by
      the pharmacological blockade of either the inositol 1,4,5-triphosphate receptor
      or the mitochondrial Ca(2+) uniporter, as well as by siRNA-dependent
      mitochondrial Ca(2+) uniporter knockdown. Norepinephrine-stimulated
      cardiomyocytes showed a significant decrease in endoplasmic reticulum
      mitochondrial contacts compared to either control or insulin like growth factor-1
      stimulated cells. This resulted in a reduction in mitochondrial Ca(2+) uptake,
      Akt activation, glucose uptake and oxygen consumption in response to insulin.
      Blocking mitochondrial Ca(2+) uptake was sufficient to mimic the effect of
      norepinephrine-induced cardiomyocyte hypertrophy on insulin signaling.
      CONCLUSIONS: Mitochondrial Ca(2+) uptake is a key event in insulin signaling and
      metabolism in cardiomyocytes.

PMID- 25376906
TI  - Perylene-diimide-based nanoparticles as highly efficient photoacoustic agents for
      deep brain tumor imaging in living mice.
AB  - In order to promote preclinical and clinical applications of photoacoustic
      imaging, novel photoacoustic contrast agents are highly desired for molecular
      imaging of diseases, especially for deep tumor imaging. Here, perylene-3,4,9,10
      tetracarboxylic diiimide-based near-infrared-absorptive organic nanoparticles are
      reported as an efficient agent for photoacoustic imaging of deep brain tumors in
      living mice with enhanced permeability and retention effect.

PMID- 25376908
TI  - Association between Pro12Ala, Pvull, Avall, Sstl and ADIPOQ single-nucleotide
      polymorphisms with lipid and glycemic profiles of patients with Berardinelli-Seip
      syndrome.
AB  - BACKGROUND/AIMS: Berardinelli-Seip syndrome (BSS) is a recessive autosomal
      genetic disorder characterized by the near loss of adipose tissue with
      disturbance in lipid metabolism. METHODS: Biochemical and hormonal parameters and
      Pro12Ala, Pvull, Avall, Sstl and ADIPOQ polymorphisms in 22 patients with BSS
      were analyzed and examined for a possible association with lipid profiles.
      RESULTS: Parental consanguinity, insulin resistance and diabetes mellitus were
      observed in 63.6, 81.8 and 59.1% of patients, respectively. All individuals
      presented high triglyceride levels, and 68.1% of patients showed high cholesterol
      levels. The Pro/Pro genotype of the Pro12Ala polymorphism of the PPARgamma2 gene
      was found in 86.3% of patients; the Ala/Ala variant was not observed in any
      patient. The PvuII polymorphism of the LPL gene showed a frequency of 50% for the
      P1P2 variant. The AvaII polymorphism of the LDLR gene showed a similar frequency
      of 40.9% for both CT and TT variants. The S1S1 genotype of the Sstl polymorphism
      of the APOC3 gene had a frequency of 86.3%. The CC allele of the ADIPOQ
      polymorphism of the adiponectin gene was found in 54.6% of patients. CONCLUSIONS:
      No association was found between lipid parameters and the relevant Pvull, Avall
      and Sstl polymorphisms. However, we did observe an association of the Pro12Ala
      and ADIPOQ polymorphisms with higher lipid levels, suggesting a close
      relationship between these factors.

PMID- 25376910
TI  - Modeling and validating Bayesian accrual models on clinical data and simulations
      using adaptive priors.
AB  - Slow recruitment in clinical trials leads to increased costs and resource
      utilization, which includes both the clinic staff and patient volunteers. Careful
      planning and monitoring of the accrual process can prevent the unnecessary loss
      of these resources. We propose two hierarchical extensions to the existing
      Bayesian constant accrual model: the accelerated prior and the hedging prior. The
      new proposed priors are able to adaptively utilize the researcher's previous
      experience and current accrual data to produce the estimation of trial completion
      time. The performance of these models, including prediction precision, coverage
      probability, and correct decision-making ability, is evaluated using actual
      studies from our cancer center and simulation. The results showed that a constant
      accrual model with strongly informative priors is very accurate when accrual is
      on target or slightly off, producing smaller mean squared error, high percentage
      of coverage, and a high number of correct decisions as to whether or not continue
      the trial, but it is strongly biased when off target. Flat or weakly informative
      priors provide protection against an off target prior but are less efficient when
      the accrual is on target. The accelerated prior performs similar to a strong
      prior. The hedging prior performs much like the weak priors when the accrual is
      extremely off target but closer to the strong priors when the accrual is on
      target or only slightly off target. We suggest improvements in these models and
      propose new models for future research.

PMID- 25376909
TI  - Polo kinase regulates the localization and activity of the chromosomal passenger
      complex in meiosis and mitosis in Drosophila melanogaster.
AB  - Cell cycle progression is regulated by members of the cyclin-dependent kinase
      (CDK), Polo and Aurora families of protein kinases. The levels of expression and
      localization of the key regulatory kinases are themselves subject to very tight
      control. There is increasing evidence that crosstalk between the mitotic kinases
      provides for an additional level of regulation. We have previously shown that
      Aurora B activates Polo kinase at the centromere in mitosis, and that the
      interaction between Polo and the chromosomal passenger complex (CPC) component
      INCENP is essential in this activation. In this report, we show that Polo kinase
      is required for the correct localization and activity of the CPC in meiosis and
      mitosis. Study of the phenotype of different polo allele combinations compared to
      the effect of chemical inhibition revealed significant differences in the
      localization and activity of the CPC in diploid tissues. Our results shed new
      light on the mechanisms that control the activity of Aurora B in meiosis and
      mitosis. 

PMID- 25376911
TI  - Antimicrobial stewardship activities: a survey of Queensland hospitals.
AB  - OBJECTIVE: In 2011, the Australian Commission on Safety and Quality in Health
      Care (ACSQHC) recommended that all hospitals in Australia must have an
      Antimicrobial Stewardship (AMS) program by 2013. Nevertheless, little is known
      about current AMS activities. This study aimed to determine the AMS activities
      currently undertaken, and to identify gaps, barriers to implementation and
      opportunities for improvement in Queensland hospitals. METHODS: The AMS
      activities of 26 facilities from 15 hospital and health services in Queensland
      were surveyed during June 2012 to address strategies for effective AMS:
      implementing clinical guidelines, formulary restriction, reviewing antimicrobial
      prescribing, auditing antimicrobial use and selective reporting of susceptibility
      results. RESULTS: The response rate was 62%. Nineteen percent had an AMS team (a
      dedicated multidisciplinary team consisting of a medically trained staff member
      and a pharmacist). All facilities had access to an electronic version of
      Therapeutic Guidelines: Antibiotic, with a further 50% developing local
      guidelines for antimicrobials. One-third of facilities had additional
      restrictions. Eighty-eight percent had advice for restricted antimicrobials from
      in-house infectious disease physicians or clinical microbiologists.
      Antimicrobials were monitored with feedback given to prescribers at point of care
      by 76% of facilities. Deficiencies reported as barriers to establishing AMS
      programs included: pharmacy resources, financial support by hospital management,
      and training and education in antimicrobial use. CONCLUSIONS: Several areas for
      improvement were identified: reviewing antimicrobial prescribing with feedback to
      the prescriber, auditing, and training and education in antimicrobial use. There
      also appears to be a lack of resources to support AMS programs in some
      facilities. WHAT IS KNOWN ABOUT THE TOPIC?: The ACSQHC has recommended that all
      hospitals implement an AMS program by 2013 as a requirement of Standard 3
      (Preventing and Controlling Healthcare-Associated Infections) of the National
      Safety and Quality Health Service Standards. The intent of AMS is to ensure
      appropriate prescribing of antimicrobials as part of the broader systems within a
      health service organisation to prevent and manage healthcare-associated
      infections, and improve patient safety and quality of care. This criterion also
      aligns closely with Standard 4: Medication Safety. Despite this recommendation,
      little is known about what AMS activities are undertaken in these facilities and
      what additional resources would be required in order to meet these national
      standards. WHAT DOES THE PAPER ADD?: This is the first survey that has been
      conducted of public hospital and health services in Queensland, a large
      decentralised state in Australia. This paper describes what AMS activities are
      currently being undertaken, identifies practice gaps, barriers to implementation
      and opportunities for improvement in Queensland hospitals. WHAT ARE THE
      IMPLICATIONS FOR PRACTITIONERS?: Several areas for improvement such as reviewing
      antimicrobial prescribing with feedback to the prescriber, auditing, and training
      and education in antimicrobial use have been identified. In addition, there
      appears to be a lack of resources to support AMS programs in some facilities.

PMID- 25376912
TI  - Admission time to hospital: a varying standard for a critical definition for
      admissions to an intensive care unit from the emergency department.
AB  - OBJECTIVE: Time spent in the emergency department (ED) before admission to
      hospital is often considered an important key performance indicator (KPI).
      Throughout Australia and New Zealand, there is no standard definition of 'time of
      admission' for patients admitted through the ED. By using data submitted to the
      Australian and New Zealand Intensive Care Society Adult Patient Database, the aim
      was to determine the differing methods used to define hospital admission time and
      assess how these impact on the calculation of time spent in the ED before
      admission to an intensive care unit (ICU). METHODS: Between March and December of
      2010, 61 hospitals were contacted directly. Decision methods for determining time
      of admission to the ED were matched to 67,787 patient records. Univariate and
      multivariate analyses were conducted to assess the relationship between decision
      method and the reported time spent in the ED. RESULTS: Four mechanisms of
      recording time of admission were identified, with time of triage being the most
      common (28/61 hospitals). Reported median time spent in the ED varied from 2.5
      (IQR 0.83-5.35) to 5.1 h (2.82-8.68), depending on the decision method. After
      adjusting for illness severity, hospital type and location, decision method
      remained a significant factor in determining measurement of ED length of stay.
      CONCLUSIONS: Different methods are used in Australia and New Zealand to define
      admission time to hospital. Professional bodies, hospitals and jurisdictions
      should ensure standardisation of definitions for appropriate interpretation of
      KPIs as well as for the interpretation of studies assessing the impact of
      admission time to ICU from the ED. WHAT IS KNOWN ABOUT THE TOPIC?: There are
      standards for the maximum time spent in the ED internationally, but these
      standards vary greatly across Australia. The definition of such a standard is
      critically important not only to patient care, but also in the assessment of
      hospital outcomes. Key performance indicators rely on quality data to improve
      decision-making. WHAT DOES THIS PAPER ADD?: This paper quantifies the variability
      of times measured and analyses why the variability exists. It also discusses the
      impact of this variability on assessment of outcomes and provides suggestions to
      improve standardisation. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?: This paper
      provides a clearer view on standards regarding length of stay in the ICU,
      highlighting the importance of key performance indicators, as well as the quality
      of data that underlies them. This will lead to significant changes in the way we
      standardise and interpret data regarding length of stay.

PMID- 25376914
TI  - The molecular structure of the left-handed supra-molecular helix of eukaryotic
      polyribosomes.
AB  - During protein synthesis, several ribosomes bind to a single messenger RNA (mRNA)
      forming large macromolecular assemblies called polyribosomes. Here we report the
      detailed molecular structure of a 100 MDa eukaryotic poly-ribosome complex
      derived from cryo electron tomography, sub-tomogram averaging and pseudo-atomic
      modelling by crystal structure fitting. The structure allowed the visualization
      of the three functional parts of the polysome assembly, the central core region
      that forms a rather compact left-handed supra-molecular helix, and the more open
      regions that harbour the initiation and termination sites at either ends. The
      helical region forms a continuous mRNA channel where the mRNA strand bridges
      neighbouring exit and entry sites of the ribosomes and prevents mRNA looping
      between ribosomes. This structure provides unprecedented insights into protein-
      and RNA-mediated inter-ribosome contacts that involve conserved sites through 40S
      subunits and long protruding RNA expansion segments, suggesting a role in
      stabilizing the overall polyribosomal assembly. 

PMID- 25376915
TI  - Risk group criteria for tailoring adjuvant treatment in patients with endometrial
      cancer: a validation study of the Gynecologic Oncology Group criteria.
AB  - OBJECTIVE: The purpose of this study is to validate the Gynecologic Oncology
      Group (GOG) criteria for adjuvant treatment in a different cohort of patients and
      to evaluate the simplified risk criteria predicting the prognosis and tailoring
      adjuvant treatment in patients with surgically staged endometrial cancer.
      METHODS: We performed a retrospective analysis of 261 consecutive patients with
      surgically staged endometrial cancer between January 2000 and February 2013. All
      patients had complete staging procedures and were surgically staged according to
      the 2009 International Federation of Gynecology and Obstetrics staging system.
      Clinical and pathologic data were obtained from medical records. We designed the
      simplified risk criteria for adjuvant treatment according to the risk factors
      associated with survival. The patients were divided into low and low
      intermediate, high-intermediate, and high-risk groups according to the GOG
      criteria and simplified criteria and their survivals were compared. Receiver
      operating characteristic curve analysis was used to evaluate the prognostic
      significance of both criteria. RESULTS: Median follow-up time was 48 months
      (range, 10 to 122 months). According to the GOG criteria, we identified 197 low
      and low-intermediate risk patients, 20 high-intermediate risk patients, and 44
      high-risk patients. There were significant differences in disease-free (p<0.001)
      and overall survival (p<0.001) among the three groups. Using the simplified risk
      criteria, we identified 189 low and low-intermediate risk patients, 28 high
      intermediate risk patients, and 44 high-risk patients. There were significant
      differences in disease-free (p<0.001) and overall survival (p<0.001) among the
      three groups. The performance of the simplified criteria (area under the curve
      [AUC]=0.829 and 0.916 for disease recurrences and deaths, respectively) was as
      good as the GOG criteria (AUC=0.836 and 0.921 for disease recurrences and deaths,
      respectively). CONCLUSION: The simplified criteria may be easily applicable and
      offer useful information for planning strategy of adjuvant treatment in patients
      with surgically staged endometrial cancer as the GOG criteria.

PMID- 25376918
TI  - Abstracts of the RCOG National Trainees Conference (NTC) 2014, 27-28 November
      2014, Manchester, United Kingdom.

PMID- 25376916
TI  - Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in
      advanced ovarian cancer: a multicenter prospective observational study.
AB  - OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) have been recently reported with favorable oncological
      outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of
      this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and
      paclitaxel for the treatment of advanced EOC. METHODS: This is a prospective
      observational study of 54 patients, from April 2007 to October 2013, with primary
      or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51+/-9.34.
      Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent
      disease. RESULTS: Mean peritoneal cancer index was 10.11 (range, 0 to 28),
      complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven
      patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not
      included in the study. The mean stay in intensive care unit was 4.73+/-5.51 days
      and the mean hospitalization time was 24.0+/-10.03 days. We did not observe any
      intraoperative death. Seven patients (13%) required additional operations. Three
      patients (5.6%) died within 30 days from the procedure. Severe complications were
      seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33
      patients (61.1%); the median disease-free survival time was 12.46 months and the
      median overall survival time was 32.91 months. CONCLUSION: CRS+HIPEC with
      cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity
      and mortality. Additional follow-up and further studies are needed to determine
      the effects of HIPEC on long term survival.

PMID- 25376917
TI  - An analysis of current treatment practice in uterine papillary serous and clear
      cell carcinoma at two high volume cancer centers.
AB  - OBJECTIVE: Despite the rarity of uterine papillary serous carcinoma (UPSC) and
      uterine clear cell carcinoma (UCCC), they contribute disproportionately to
      endometrial cancer deaths. Sufficient clinical information regarding treatment
      and prognosis is lacking. The aim of this study is to evaluate treatment outcomes
      in a rare cancer cohort based on the experience at two tertiary care cancer
      centers. METHODS: Clinicopathologic data were retrospectively collected on 279
      patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of
      adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for
      their association with overall survival (OS) and progression-free survival (PFS).
      RESULTS: 40.9% of patients presented with stage I disease, 6.8% of patients
      presented with stage II disease and 52.3% of patients presented with stages III
      and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5
      years were 63.0% and 51.9%, respectively. OS and PFS were not affected by mode of
      surgery (open vs. robotic approach; OS: hazard ratio [HR], 0.68; 95% confidence
      interval [CI], 0.28 to 1.62; PFS: HR, 0.78; 95% CI, 0.40 to 1.56). Adjuvant
      treatment was associated with improved OS in stages IB-II (HR, 0.14; 95% CI, 0.02
      to 0.78; p=0.026) but not in stage IA disease. There was no difference in OS or
      PFS based on the performance of a paraaoritc lymph node dissection. CONCLUSION:
      Minimally invasive surgical staging appears a reasonable strategy for patients
      with non-bulky UPSC and UCCC and was not associated with diminished survival.
      Adjuvant treatment improved 5-year survival in stages IB-II disease.

PMID- 25376919
TI  - Antifungal efficiency of miconazole and econazole and the interaction with
      transport protein: a comparative study.
AB  - CONTEXT: Miconazole (MIZ) and econazole (ECZ) are clinically used as antifungal
      drugs. OBJECTIVE: The drug effect and binding property with transport protein
      human serum albumin of MIZ and ECZ were studied. MATERIALS AND METHODS: The
      antifungal efficiency was investigated by microdiluting drug solutions from 0 to
      48 MUmol L(-1) through microcalorimetry and voltammetry studies. Transmission
      electron microscopy was used for morphological observations of C. albicans. The
      interaction with HSA was studied by electrochemical methods, fluorescence
      spectrometry, electron microscopy, and molecular simulation. RESULTS: IC50 of MIZ
      and ECZ for C. albicans were obtained as 19.72 and 29.90 MUmol L(-1). Binding
      constants of MIZ and ECZ with HSA of 2.36 * 10(4) L mol(-1) and 3.73 * 10(4) L
      mol(-1) were obtained. After adding MIZ solution of 12 and 40 MUmol L(-1), the
      peak currents increased to 4.887 and 6.024 MUA. The peak currents of C. albicans
      in the presence of 20 and 48 MUmol L(-1) ECZ were 4.701 and 5.544 MUA. The
      docking scores for MIZ and ECZ of the best binding conformation in site I and
      site II were 5.60, 4.79, 5.63, and 5.85. DISCUSSION AND CONCLUSION: Strong
      inhibition to the metabolism of C. albicans and destructive effect was proved for
      both drugs. The lower IC50, growth rate constant of C. albicans, and higher peak
      current, reveal stronger antifungal activity of MIZ. Both drugs show an efficient
      quenching effect to intrinsic fluorescence residues of protein. MIZ mainly binds
      on site I while ECZ on site II. Molecular modeling experiments give further
      insight of the binding mechanism.

PMID- 25376920
TI  - Stem cell therapies for systemic sclerosis.
AB  - The presence of autoimmune diseases, including Systemic Sclerosis (SSc), suggest
      failure of the normal immune regulatory processes leading to activation and
      expansion of autoreactive effector immune cells. Recently, stem cell
      transplantation emerged as a novel rescue therapy for a variety of refractory
      autoimmune diseases. The therapeutic strategy involves the ablation of the
      aberrant self-reactive immune cells by chemotherapy and the regeneration of a new
      self-tolerant immune system formed by the transplanted stem cells. In the last
      few years, thousands of patients worldwide have received haematopoietic stem cell
      transplantation (HSCT), mostly autologous, as treatment for severe irreversible
      autoimmune diseases, with promising results. Here we review the results of
      published small series of SSc patients treated with allogeneic and autologous
      HSCT, as well as three randomized trials, exploring the safety and efficacy of
      autologous HSCT in SSc. Although the results are encouraging, nonetheless, the
      correct application of stem cell transplantation remains an area of active
      investigation. Results of larger randomized, double blind clinical trials, will
      certainly improve our knowledge of the appropriate clinical use of stem cell
      therapy in SSc patients. 

PMID- 25376921
TI  - A study exploring attributes and nature of the retracted literature on mental
      disorders.
AB  - This study was aimed at assessing the retracted medical literature on mental
      disorders. Another aim was to test the hypothesis that the weak research
      infrastructure in certain countries and the rising pressure to publish in Asia
      due to the progress of science in that continent may have contributed to the
      increase in the number of retractions. A bibliometric search was carried out
      using the PubMed database. The data were analysed using SPSS version 21. The
      retraction rate for articles on mental disorders (number of retracted articles
      per 100,000 published articles on mental disorders) varied from a low of 3.56
      (for 2005) to a high of 49.25 (for 2012). Of the 38 articles for which the
      reasons for retraction could be accessed, 10 (26.31%) were retracted for fraud.
      Overall, 0.0138% of all articles on the biomedical sciences were retracted. Of
      the articles on mental disorders, 0.0095% were retracted. There was a
      disproportionately greater number of retractions in the case of articles
      originating from low- and middle-income countries than high-income countries.
      Similarly, there was a disproportionately greater number of retractions in the
      case of articles originating in Asian countries than non-Asian countries. 

PMID- 25376922
TI  - The SUPPORT controversy and learnings.

PMID- 25376923
TI  - Efficacy and Safety of Augmenting the Preclose Technique with a Collagen-Based
      Closure Device for Percutaneous Endovascular Aneurysm Repair.
AB  - PURPOSE: To report our experience of selectively augmenting the preclose
      technique for percutaneous endovascular aneurysm repair (p-EVAR) with an Angio
      Seal device as a haemostatic adjunct in cases of significant bleeding after
      tensioning the sutures of the suture-mediated closure devices. MATERIALS AND
      METHODS: Prospectively collected data for p-EVAR patients at our institute were
      analysed. Outcomes included technical success and access site complications. A
      logistic regression model was used to analyse the effects of sheath size, CFA
      features and stent graft type on primary failure of the preclose technique
      necessitating augmentation and also on the development of complications. RESULTS:
      p-EVAR was attempted via 122 CFA access sites with a median sheath size of 18
      French (range 12- to 28-French). Primary success of the preclose technique was
      75.4% (92/122). Angio-Seal augmentation was utilised as an adjunct to the
      preclose technique in 20.5% (25/122). The overall p-EVAR success rate was 95.1%
      (116/122). There was a statistically significant relationship (p = 0.0093)
      between depth of CFA and primary failure of preclose technique. CFA diameter,
      calcification, type of stent graft and sheath size did not have significant
      effects on primary preclose technique failure. Overall 4.9% (6/122) required
      surgical conversion but otherwise there were no major complications. CONCLUSION:
      Augmentation with an Angio-Seal device is a safe and effective adjunct to
      increase the success rate of the preclose technique in p-EVAR.

PMID- 25376925
TI  - Factors shaping intersectoral action in primary health care services.
AB  - OBJECTIVE: To examine case studies of good practice in intersectoral action for
      health as one part of evaluating comprehensive primary health care in six sites
      in South Australia and the Northern Territory. METHODS: Interviews with primary
      health care workers, collaborating agency staff and service users (Total N=33);
      augmented by relevant documents from the services and collaborating partners.
      RESULTS: The value of intersectoral action for health and the importance of
      partner relationships to primary health care services were both strongly
      endorsed. Factors facilitating intersectoral action included sufficient human and
      financial resources, diverse backgrounds and skills and the personal rewards that
      sustain commitment. Key constraining factors were financial and time limitations,
      and a political and policy context which has become less supportive of
      intersectoral action; including changes to primary health care. CONCLUSIONS:
      While intersectoral action is an effective way for primary health care services
      to address social determinants of health, commitment to social justice and to
      adopting a social view of health are constrained by a broader health service now
      largely reinforcing a biomedical model. IMPLICATIONS: Effective organisational
      practices and policies are needed to address social determinants of health in
      primary health care and to provide a supportive context for workers engaging in
      intersectoral action.

PMID- 25376924
TI  - Comparison of CT Fluoroscopy-Guided Manual and CT-Guided Robotic Positioning
      System for In Vivo Needle Placements in Swine Liver.
AB  - PURPOSE: To compare CT fluoroscopy-guided manual and CT-guided robotic
      positioning system (RPS)-assisted needle placement by experienced IR physicians
      to targets in swine liver. MATERIALS AND METHODS: Manual and RPS-assisted needle
      placement was performed by six experienced IR physicians to four 5 mm fiducial
      seeds placed in swine liver (n = 6). Placement performance was assessed for
      placement accuracy, procedure time, number of confirmatory scans, needle
      manipulations, and procedure radiation dose. Intra-modality difference in
      performance for each physician was assessed using paired t test. Inter-physician
      performance variation for each modality was analyzed using Kruskal-Wallis test.
      RESULTS: Paired comparison of manual and RPS-assisted placements to a target by
      the same physician indicated accuracy outcomes was not statistically different
      (manual: 4.53 mm; RPS: 4.66 mm; p = 0.41), but manual placement resulted in
      higher total radiation dose (manual: 1075.77 mGy/cm; RPS: 636.4 mGy/cm; p =
      0.03), required more confirmation scans (manual: 6.6; RPS: 1.6; p < 0.0001) and
      needle manipulations (manual: 4.6; RPS: 0.4; p < 0.0001). Procedure time for RPS
      was longer than manual placement (manual: 6.12 min; RPS: 9.7 min; p = 0.0003).
      Comparison of inter-physician performance during manual placement indicated
      significant differences in the time taken to complete placements (p = 0.008) and
      number of repositions (p = 0.04) but not in other study measures (p > 0.05).
      Comparison of inter-physician performance during RPS-assisted placement suggested
      statistically significant differences in procedure time (p = 0.02) and not in
      other study measures (p > 0.05). CONCLUSIONS: CT-guided RPS-assisted needle
      placement reduced radiation dose, number of confirmatory scans, and needle
      manipulations when compared to manual needle placement by experienced IR
      physicians, with equivalent accuracy.

PMID- 25376926
TI  - Giving "Sadness" a Name: The Need for Integrating Depression Treatment into HIV
      Care in Uganda.
AB  - Depression is common among people living with HIV/AIDS (PLWHA) in sub-Saharan
      Africa (SSA), and can have significant consequences for HIV disease progression,
      treatment response and prevention. Yet mental health services are limited in most
      HIV care programs in this region, in part due to severe shortages of mental
      health professionals. To address the need for establishing an effective,
      sustainable model for integrating depression treatment into HIV care in SSA, we
      have embarked upon a 3-year research project, INDEPTH Uganda (INtegrating
      DEPression Treatment and in HIV care in Uganda), to evaluate a task-sharing,
      protocolized approach to providing antidepressant care in ten HIV clinics in
      Uganda. In this paper we share our experiences with two treated cases identified
      during the initial days of implementation, which we believe highlight the
      potential value and policy implications for task shifting depression care models
      in under-resourced settings. 

PMID- 25376928
TI  - Motor cortical excitability in peritoneal dialysis: a single-pulse TMS study.
AB  - The aim of this paper is to investigate cortical excitability in patients with
      end-stage renal disease receiving peritoneal dialysis (PD) without any symptoms
      suggestive of uremic encephalopathy. We performed transcranial magnetic
      stimulation for 52 PD patients and 28 normal subjects. We compared the active
      motor threshold (AMT), resting motor threshold (RMT), root latency, central motor
      conduction time (CMCT), and cortical silent period (CSP) in PD patients to those
      in normal subjects. AMT, RMT, CMCT, and CSP were not significantly different
      between PD patients and normal subjects. However, root latency was significantly
      prolonged in PD patients compared to normal subjects. The root latency correlated
      linearly with HbA1c or duration of PD in the patients. The results suggest that
      the corticospinal tract and the cortical and spinal excitabilities are preserved
      but the peripheral nerves are disturbed in PD patients. The severity of
      peripheral neuropathy corresponds to the severity of DM and the duration of PD.
      We uncovered no evidence suggestive of any subclinical abnormality of the motor
      cortical excitability in PD patients. 

PMID- 25376927
TI  - Proposed new lymphology combined with lymphatic physiology, innate immunology,
      and oncology.
AB  - As one of the lymphatic functions, it is well known that the transport and
      drainage of hydrophilic substances including plasma protein through the lymphatic
      system play pivotal roles in maintaining the homeostasis of the internal
      environment between the cells in tissues in collaboration with the exchange of
      the substances through the blood capillaries and venules. The physiological
      functions of the lymphatic system have been studied by many investigations of
      microcirculation, i.e., Yoffey and Courtice, Ruszunyak et al., Foldie and Casley
      Smigh et al., Roddie, Schmid-Schonbein et al., and Ohhashi et al. On the other
      hand, it is also well known that the initial clinical signs of primary diseases
      such as inflammation, tumors, and circulatory disorders including infarction and
      thrombosis appear as functional abnormalities of the internal environment in
      tissues. These abnormalities of the functions are strongly related to
      immunological defense reactions around the internal environment and abnormal
      actions of the transport and drainage of the lymphatic system. Taking into
      consideration the current inspired findings in lymphatic physiology, innate
      immunology, and oncology, we have proposed a new lymphology combined with new
      knowledge of the three above-mentioned academic fields from a defense mechanism
      points of view. In this review, we would like to demonstrate comprehensively our
      latest studies related to the possibility of establishing a new lymphology,
      hoping the readers will evaluate this possibility.

PMID- 25376929
TI  - Pro-elastogenic effects of bone marrow mesenchymal stem cell-derived smooth
      muscle cells on cultured aneurysmal smooth muscle cells.
AB  - Abdominal aortic aneurysms (AAAs) involve slow proteolysis and loss of structural
      matrix components (collagen and elastin), which lead to wall thinning, weakening
      and ultimate rupture. At this time, no established non-surgical therapy is
      available to slow or arrest AAA growth. Inhibiting matrix metalloproteases (MMPs;
      e.g. MMP2 and -9) overexpressed within AAAs is insufficient to arrest AAA growth,
      since resident smooth muscle cells (SMCs) are poorly elastogenic and cannot
      overcome elastolysis to reinstate a healthy elastic matrix. Towards overcoming
      this limitation, this first study sought to determine the utility of rat bone
      marrow mesenchymal stem cell (BM-MSC)-derived SMCs to stimulate elastin and
      elastic matrix synthesis and assembly by aneurysmal SMCs (EaRASMCs). BM-MSCs were
      successfully differentiated into cells of an SMC lineage (SMLCs). Our study
      indicates that BM-MSC-derived SMLCs secrete trophic factors, contained in
      conditioned medium (CM) from their cultures, that, when exposed to EaRASMC
      cultures in real time, stimulate elastin precursor and matrix deposition and
      crosslinking by these elastogenically deficient cells, with added benefits in
      terms of attenuating MMPs, specifically MMP9. The results thus lend support to a
      proposed cell therapy for AAAs, based on the use of BM-MSC-derived SMLCs.
      Although we observed no particular improvement in elastic fibre formation, no
      attenuation of MMP2 activity and increase in amounts of active MMP2 enzyme, we
      believe that this study justifies follow-up studies to improve upon these
      outcomes. Future studies will explore the effects of concentrated CM collected
      from long-term SMLC cultures on EaRASMCs and also investigate the elastogenic
      output of SMLCs themselves. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25376930
TI  - Effect of rivastigmine or memantine add-on therapy is affected by
      butyrylcholinesterase genotype in patients with probable Alzheimer's disease.
AB  - BACKGROUND: The K variant of butyrylcholinesterase (BCHE-K) exhibits a reduced
      acetylcholine-hydrolyzing capacity; so the clinical response to rivastigmine may
      differ in Alzheimer's disease (AD) patients with the BCHE-K gene. OBJECTIVE: To
      investigate the clinical response to rivastigmine transdermal patch monotherapy
      or memantine plus rivastigmine transdermal patch therapy in AD patients based on
      the BCHE-K gene. METHODS: A total of 146 probable AD patients consented to
      genetic testing for butyrylcholinesterase and underwent the final efficacy
      evaluations. Responders were defined as patients with an equal or better score on
      the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) at 16
      weeks compared to their baseline score. RESULTS: BCHE-K carriers showed a lower
      responder rate on the ADAS-cog than non-carriers (38.2 vs. 61.7%, p = 0.02), and
      this trend was evident in AD patients with apolipoprotein E epsilon 4 (35 vs.
      60.7%, p = 0.001). The presence of the BCHE-K allele predicted a worse response
      on the ADAS-cog (odds ratio 0.35, 95% confidence interval 0.14-0.87), after
      adjusting for demographic and baseline cognitive and functional variables.
      CONCLUSION: The BCHE-K genotype may be related to a poor cognitive response to
      rivastigmine patch or memantine add-on therapy, especially in the presence of
      apolipoprotein E epsilon 4.

PMID- 25376931
TI  - Distorting the history of evolutionary thought in conceptual development
      research.

PMID- 25376932
TI  - Temperature dependence and P/Ti ratio in phosphoric acid treatment of titanium
      dioxide and powder properties.
AB  - OBJECTIVE: Titanium dioxide has photocatalytic activity and is used as a white
      pigment for cosmetics. A certain degree of sebum on the skin is decomposed by the
      ultraviolet radiation in sunlight. In this work, titanium dioxide was shaken with
      phosphoric acid to synthesize a white pigment for cosmetics. METHODS: Titanium
      dioxide was treated with 0.1 mol/L of phosphoric acid at various P/Ti molar
      ratios, and then shaken in hot water for 1 h. The chemical composition, powder
      properties, photocatalytic activity, colour phase, and smoothness of the obtained
      powder were studied. RESULTS: The obtained materials indicated XRD peaks of
      titanium dioxide, however the peaks diminished subsequent to phosphoric acid
      treatment. The samples included small particles with sub-micrometer size. The
      photocatalytic activity of the obtained powders decreased, decomposing less sebum
      on the skin. Samples prepared at high P/Ti ratio with high shaking temperature
      indicated low whiteness in in L*a*b* colour space. The shaking and heating
      temperature and P/Ti ratio had influence on the smoothness of the obtained
      materials. CONCLUSION: Phosphoric acid treatment of titanium dioxide is an
      effective method to inhibit photocatalytic activity for a white pigment.

PMID- 25376933
TI  - Increased macrophage activation inhibited by tacrolimus in the kidney of diabetic
      rats.
AB  - BACKGROUND/AIMS: Accumulating evidence suggests that macrophage-induced
      inflammation may be the mechanism of development and progression of diabetic
      nephropathy. A previous study by our group has shown that tacrolimus, like
      cyclosporin A, has a renoprotective effect in diabetic rats. The present study
      aimed to elucidate the underlying molecular events. METHODS: Diabetic rats were
      induced by using streptozotocin. Diabetic rats were subjected to oral tacrolimus
      treatment at a dose of 0.5 or 1.0 mg/kg daily for 4 weeks. Body weight, blood
      glucose, hemoglobin A(1c) (HbA(1c)) and renal pathology were assessed, followed
      by analyses of renal calcineurin (CaN) expression, changes in renal macrophage
      infiltration, proliferation and activation, and detection of renal TLR2+ and
      TLR4+ as well as NF-kappaB-p-p65+ in macrophages. RESULTS: Diabetic rats had a
      reduced body weight and increased blood glucose and HbA(1c) levels, whereas
      tacrolimus treatment did not affect body weight or blood glucose and HbA(1c).
      Increased relative kidney weight was only significantly reduced by tacrolimus
      treatment at a dose of 1.0 mg/kg, while the elevated albumin excretion rate was
      markedly attenuated after treatment with tacrolimus (0.5 and 1.0 mg/kg) in
      diabetic rats. Elevated glomerular volume was significantly attenuated by
      tacrolimus treatment with 0.5 and 1.0 mg/kg, and increased indices for
      tubulointerstitial injury were only ameliorated by tacrolimus treatment with 1.0
      mg/kg. Western blot data showed that expression of CaN protein was induced 2.4
      fold in the kidneys of positive control diabetic rats, whereas tacrolimus
      treatment at 0.5 and 1.0 mg/kg doses reduced the increased expression of CaN
      protein by 38.0 and 73.2%, respectively. Histologically there was a marked
      accumulation of ED-1+ cells (macrophages) in diabetic kidneys and tacrolimus
      treatment failed to inhibit it. In contrast, tacrolimus treatment at 0.5 and 1.0
      mg/kg doses significantly inhibited the elevated ED-1+/PCNA+ cells and ED
      1+/iNOS+ cells in the kidneys of diabetic rats, while tacrolimus treatment at a
      dose of 0.5 or 1.0 mg/kg significantly suppressed the increased ED-1+/TLR2+
      cells, ED-1+/TLR4+ cells and ED-1+/NF-kappaB-p-p65+ cells in the kidneys of
      diabetic rats. CONCLUSION: The data from the current study demonstrated that
      tacrolimus could ameliorate early renal injury through a mechanism to suppress
      macrophage activation.

PMID- 25376935
TI  - Surface acidity of quartz: understanding the crystallographic control.
AB  - We report a first principles molecular dynamics (FPMD) study of surface acid
      chemistry of the two growth surfaces of quartz, (1010) (including Alpha and Beta
      terminations) and (1011) facets. The interfacial hydration structures are
      characterized in detail and the intrinsic pKas of surface silanols are evaluated
      using the FPMD based vertical energy gap method. The calculated acidity constants
      reveal that every surface termination shows a bimodal acid-base behavior. It is
      found that all doubly-protonated forms (i.e. SiOH2) on the three terminations
      have pKas lower than -2.5, implying that the silanols hardly get protonated in a
      common pH range. The pKas of surface silanols can be divided into 3 groups. The
      most acidic silanol is the donor SiOH on the (1010)-beta surface (pKa = 4.8), the
      medium includes the germinal silanol on (1010)-alpha and the outer silanol on
      (1011) (pKa = 8.5-9.3) and the least acidic are inner silanols on the (1011)
      facet, acceptor SiOH on (1010)-beta, and the secondly-deprotonated OH (i.e. Si(O
      )(OH)) on (1010)-alpha (pKa > 11.0). With the pKa values, we discuss the
      implication for understanding metal cations complexing on quartz surfaces.

PMID- 25376934
TI  - Evaluation of a new method of irrigation and aspiration for removal of ophthalmic
      viscoelastic device during cataract surgery in a porcine model.
AB  - BACKGROUND: To determine if a method for irrigation and aspiration (I/A) during
      cataract surgery provides effective removal of ophthalmic viscoelastic device
      (OVD). METHODS: Japanese porcine eyes were used to evaluate I/A performance with
      Technique 1 (the I/A tip placed on the center of the anterior surface of the
      IOL), Technique 2 (the I/A tip alternately pressed near the edge of the IOL optic
      anterior surface on one side and then the other to tilt the IOL back and forth),
      and Technique 3 (the I/A tip inserted behind the IOL optic, between it and the
      posterior capsule). Techniques 1 and 2 were compared using the Miyake-Apple
      posterior view video technique to visualize the flow of irrigation fluid
      containing triamcinolone acetonide particles behind the IOL. To check the
      efficacy of OVD removal from behind the IOL for of all three I/A techniques, OVD
      with fluorescein beads were inserted inside the lens capsule before implantation
      of the IOL. After each I/A technique, eyes were prepared for Miyake-Apple viewing
      and pictures of the lens capsule were taken using fluorescent microscopy.
      Residual fluorescein beads in the capsular bag were analyzed. RESULTS: Technique
      1 resulted in a straight flow of fluid behind the IOL, while Technique 2 resulted
      in a vortex flow. The average amount of OVD retained inside the capsule after
      using Technique 2 or 3 was significantly lower than after using Technique 1 (p
      <0.0001). CONCLUSIONS: Technique 2 proved to remove more effectively fluorescein
      bead-labelled OVD under the IOL than Technique 1.

PMID- 25376936
TI  - Synthesis of a pentasaccharide and neoglycoconjugates related to fungal alpha-(1
      >3)-glucan and their use in the generation of antibodies to trace Aspergillus
      fumigatus cell wall.
AB  - 3-Aminopropyl alpha-(1->3)-pentaglucoside, a fragment of alpha-(1->3)-glucan of
      the cell wall of Aspergillus fumigatus, has been synthesized in a blockwise
      approach. The application of mono- and disaccharide N-phenyltrifluoroacetimidates
      bearing a stereodirecting 6-O-benzoyl group was essential for stereoselective
      alpha-glucosylations. In the products, p-methoxyphenyl and levulinoyl groups
      served as orthogonal protecting groups for the anomeric position and 3-OH group,
      respectively. Their removal from shared blocks led to donors and acceptors that
      were used for the synthesis of pentasaccharides. Coupling of free alpha-(1->3)
      pentaglucoside with biotin and bovine serum albumin (BSA) gave glycoconjugate
      tools for mycological studies. Immunization of mice with the BSA conjugate
      induced the generation of antibodies that recognize alpha-(1->3)-glucan on A.
      fumigatus cell wall and distinguish its morphotypes. This discovery represents a
      first step to the development of a diagnostic test system and a vaccine to detect
      and fight this life-threatening pathogen. 

PMID- 25376937
TI  - Effects of Treg cells and IDO on human epithelial ovarian cancer cells under
      hypoxic conditions.
AB  - The aim of the present study was to explore the effect of hypoxia on ovarian
      cancer. A total of 6 samples were analyzed: SKOV3-IP cells (ovarian cancer cell
      line); SKOV3-IP and regulatory T (Treg) cells; SKOV3-IP and cytotoxic T
      lymphocytes (CTLs); SKOV3-IP and natural killer (NK) cells; SKOV3-IP co-cultured
      with CTLs and Treg cells; and SKOV3-IP co-cultured with Treg cells and NK cells.
      The expression of indoleamine 2,3-dioxygenase (IDO) was detected by reverse
      transcription-polymerase chain reaction (RT-PCR) and western blot analysis. An
      enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of
      transforming growth factor-beta (TGF-beta), interferon-gamma (IFN-gamma),
      interleukin-2 (IL-2), interleukin-10 (IL-10), and perforin. Moreover, ovarian
      cancer cell apoptosis and invasive ability were examined using flow cytometry and
      a Transwell chamber assay. IDO expression was significantly reduced in hypoxia
      and enhanced by Treg cells. Treg cells inhibited the IL-2, IFN-gamma and perforin
      secretion, and significantly (P<0.05) increased the IL-10 and TGF-beta levels.
      The effects of Treg cells were enhanced with prolongation of the cell exposure to
      hypoxic conditions. In addition, Treg cells attenuated the promotive effect of
      CTLs and NK cells on cancer cell apoptosis. In addition, Treg cells significantly
      increased the SKOV3-IP invasive ability (P=0.00109) under hypoxic conditions. Our
      results suggest that IDO and Treg cells may serve as important therapeutic
      targets for patients with ovarian cancer.

PMID- 25376938
TI  - Design of three-shell icosahedral matryoshka clusters A@B12@A220 (A = Sn, Pb; B =
      Mg, Zn, Cd, Mn).
AB  - We propose a series of icosahedral matryoshka clusters of A@B12@A20 (A = Sn, Pb;
      B = Mg, Zn, Cd), which possess large HOMO-LUMO gaps (1.29 to 1.54 eV) and low
      formation energies (0.06 to 0.21 eV/atom). A global minimum search using a
      genetic algorithm and density functional theory calculations confirms that such
      onion-like three-shell structures are the ground states for these A21B12 binary
      clusters. All of these icosahedral matryoshka clusters, including two previously
      found ones, i.e., [As@Ni12@As20](3-) and [Sn@Cu12@Sn20](12-), follow the 108
      electron rule, which originates from the high Ih symmetry and consequently the
      splitting of superatom orbitals of high angular momentum. More interestingly, two
      magnetic matryoshka clusters, i.e., Sn@Mn12@Sn20 and Pb@Mn12@Pb20, are designed,
      which combine a large magnetic moment of 28 uB, a moderate HOMO-LUMO gap, and
      weak inter-cluster interaction energy, making them ideal building blocks in novel
      magnetic materials and devices.

PMID- 25376939
TI  - Computational identification and experimental validation of microRNAs binding to
      the fragile X syndrome gene Fmr1.
AB  - MicroRNAs (miRNAs) usually bind to their target mRNAs through imperfect base
      pairing in the 3'-untranslated regions (3' UTRs) and regulate target gene
      expression via post-transcriptional suppression. In recent years, computational
      approaches to predict miRNA targets have facilitated the identification of
      potential target sites. In this study, we used three programs TargetScan, miRDB
      and miRanda to predict potential miRNA binding sites to the fragile X gene Fmr1
      and picked out 61 miRNAs which were predicted by all three programs for further
      investigation. Excitingly, 5 out of these miRNAs, miR-23a, miR-32, miR-124, miR
      335-5p and miR-350, were experimentally verified by luciferase reporter assays.
      Furthermore, overexpression of miR-124 in mouse embryonic neural progenitor cells
      (eNPC) could not only significantly reduce Fmr1 level, but also increase Cdk4 and
      cyclin D1 levels which coincidently promoted eNPC proliferation. Our results
      imply that miR-124 plays an important role in the proliferation of mouse
      embryonic stem cells by promoting Cdk4 and cyclin D1 expression through directly
      inhibiting Fmr1 expression.

PMID- 25376941
TI  - Why care about aquatic insects: uses, benefits, and services.
AB  - Aquatic insects are common subjects of ecological research and environmental
      monitoring and assessment. However, their important role in protecting and
      restoring aquatic ecosystems is often challenged because their benefits and
      services to humans are not obvious to decision makers or the public. Insects are
      food for fish, amphibians, and wildlife. They are important contributors to
      energy and nutrient processing, including capturing nutrients and returning them
      to terrestrial ecosystems and purifying water. They provide recreation to
      fishermen and nature lovers and are cultural symbols. Monetary benefits to
      fishermen can be quantified, but most other benefits have been described
      qualitatively. Integr Environ Assess Manag 2015;11:188-194.

PMID- 25376940
TI  - Control of fluid balance guided by body composition monitoring in patients on
      peritoneal dialysis (COMPASS): study protocol for a randomized controlled trial.
AB  - BACKGROUND: The clinical benefits of bioimpedance spectroscopy (BIS)-guided fluid
      management in patients on hemodialysis have been widely demonstrated. However, no
      previous reports have evaluated the effect of regular and serial BIS-guided fluid
      management on the residual renal function (RRF) in patients on peritoneal
      dialysis (PD). Therefore, we will evaluate the clinical efficacy of BIS-guided
      fluid management for preserving RRF and protecting cardiovascular events in
      patients on PD. METHODS/DESIGN: This is a multicenter, prospective, randomized
      controlled trial. A total of 138 participants on PD will be enrolled and randomly
      assigned to receive either BIS-guided fluid management or fluid management based
      only on the clinical information for 1 year. The primary outcome is the change in
      the glomerular filtration rate (GFR) between months 0 and 12 after starting
      treatment. The secondary outcomes will include GFR at month 12, time to the
      anuric state (urine volume <100 ml/day), and fatal and nonfatal cardiovascular
      events during treatment. DISCUSSION: This is the first clinical trial to
      investigate the effect of BIS-guided fluid management on RRF and for protecting
      against cardiovascular events in patients on PD. TRIAL REGISTRATION: Clinical
      Trials.gov number NCT01887262, June 24, 2013.

PMID- 25376943
TI  - Inflammatory skin disease summit: the translational revolution, november 19 - 21,
      2014, austrian academy of sciences, dr. Ignaz seipel-platz 2, vienna, austria.

PMID- 25376942
TI  - Proliferation and osteogenic differentiation of mesenchymal stem cells induced by
      a short isoform of NELL-1.
AB  - Neural epidermal growth factor-like (NEL)-like protein 1 (NELL-1) has been
      identified as an osteoinductive differentiation factor that promotes mesenchymal
      stem cell (MSC) osteogenic differentiation. In addition to full-length NELL-1,
      there are several NELL-1-related transcripts reported. We used rapid
      amplification of cDNA ends to recover potential cDNA of NELL-1 isoforms. A NELL-1
      isoform with the N-terminal 240 amino acid (aa) residues truncated was
      identified. While full-length NELL-1 that contains 810 aa residues (NELL-1810 )
      plays an important role in embryologic skeletal development, the N-terminal
      truncated NELL-1 isoform (NELL-1570 ) was expressed postnatally. Similar to NELL
      1810 , NELL-1570 induced MSC osteogenic differentiation. In addition, NELL-1570
      significantly stimulated MSC proliferation in multiple MSC-like populations such
      as murine C3H10T1/2 MSC cell line, mouse primary MSCs, and perivascular stem
      cells, which is a type of stem cells proposed as the perivascular origin of MSCs.
      In contrast, NELL-1810 demonstrated only limited stimulation of MSC
      proliferation. Similar to NELL-1810 , NELL-1570 was found to be secreted from
      host cells. Both NELL-1570 expression lentiviral vector and column-purified
      recombinant protein NELL-1570 demonstrated almost identical effects in MSC
      proliferation and osteogenic differentiation, suggesting that NELL-1570 may
      function as a pro-osteogenic growth factor. In vivo, NELL-1570 induced
      significant calvarial defect regeneration accompanied by increased cell
      proliferation. Thus, NELL-1570 has the potential to be used for cell-based or
      hormone-based therapy of bone regeneration.

PMID- 25376944
TI  - Antitachycardia pacemakers in congenital heart disease.
AB  - BACKGROUND: Many patients with congenital heart disease (CHD) acquire rhythm
      abnormalities related to their repair, most commonly intraatrial reentrant
      tachycardia (IART). Treatment of IART in CHD is often multifaceted, and may
      include medication, ablation, and pacing. Evidence regarding the use of
      antitachycardia pacing therapies is limited. OBJECTIVE: The aim of the study is
      to define the use and efficacy of antitachycardia pacing in patients with CHD at
      a single center. RESULTS: Eighty implants were performed on 72 patients between
      2000 and 2010. Follow-up data of more than 3 months were available for 56
      patients; median follow-up time was 2.8 years. Twenty (36%) patients received
      successful antitachycardia pacing at a median 1.3 years postimplant. For those
      patients with IART after implant, antitachycardia pacing was successful in 57%.
      Patients with two-ventricle repairs were more likely to have successful
      antitachycardia pacing than those with one-ventricle palliation (45% vs. 17%, P =
      .04). Patients with documented IART had more successful antitachycardia pacing
      than those with no documented atrial tachycardia prior to implant (46% vs. 7%, P
      = .006). Early complications of antitachycardia pacemaker implant occurred in six
      patients (11%); late complications after implant occurred in three patients
      (5.6%). Of the initial 72 patients implanted, there were six deaths (8%).
      CONCLUSIONS: Antitachycardia pacing therapies were successful in the majority of
      CHD patients who had IART after implant. Patients without documented atrial
      tachycardia prior to implant were unlikely to require or receive successful
      therapy from antitachycardia pacemaker. Those patients postatrial switch
      procedure who had documented IART prior to implant had the highest incidence of
      successful antitachycardia pacing therapies. Antitachycardia pacemaker
      implantation is an adjunct to the management of IART in CHD patients, but may not
      benefit patients who have not yet demonstrated IART.

PMID- 25376945
TI  - Analgesic use matters: a response to Dr. Yoshihara.

PMID- 25376947
TI  - Novel effective drugs for diabetic kidney disease? or not?
AB  - INTRODUCTION: Diabetes mellitus is increasingly common worldwide and is expected
      to affect 592 million people by 2035. The kidney is often involved. A key goal in
      treating diabetes is to reduce the risk of development of kidney disease and, if
      kidney disease is already present, to delay the progression to end-stage renal
      disease (ESRD). This represents a social and ethical issue, as a significant
      proportion of patients reaching ESRD in developing countries do not have access
      to renal replacement therapy. AREAS COVERED: The present review focuses on novel
      therapeutic approaches for diabetic nephropathy (DN), implemented on the basis of
      recent insights on its pathophysiology, which might complement the effects of
      single inhibition of the renin-angiotensin-aldosterone system (RAAS), the
      cornerstone of renoprotective interventions in diabetes, along with glycemic and
      blood pressure control. EXPERT OPINION: Although a plethora of new treatment
      options has arisen from experimental studies, the number of novel renoprotective
      molecules successfully implemented in clinical practice over the last two decades
      is disappointingly low. Thus, new investigational strategies and diagnostic tools
      - including the appropriate choice of relevant renal end points and the study of
      urinary proteome of patients - will be as important as new therapeutic
      interventions to fight DN. Finally, in spite of huge financial interests in
      replacing the less expensive ACE inhibitors and angiotensin II receptor blockers
      with newer drugs, any future therapeutic approach has to be tested on top of -
      rather than instead of - optimal RAAS blockade.

PMID- 25376946
TI  - Enhanced expression of SAM-pointed domain-containing Ets-like factor in chronic
      rhinosinusitis with nasal polyps.
AB  - OBJECTIVE/HYPOTHESIS: Chronic rhinosinusitis with nasal polyps (CRSwNP) is
      characterized by significant goblet hyperplasia and mucus hypersecretion.
      However, the molecular mechanism underlying mucin overexpression in CRSwNP has
      not been well characterized. This study sought to assess the expression of SAM
      pointed domain-containing Ets-like factor (SPDEF) and its regulation of mucin
      production in CRSwNP patients. STUDY DESIGN: Prospective laboratory-based study.
      METHODS: Polyp and control nasal tissues were collected from 27 CRSwNP patients
      and 15 control subjects. The expression of SPDEF and MUC5AC in the nasal tissues
      was examined by immunohistochemistry staining, quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) and western blotting. In addition, SPDEF and
      MUC5AC expression was evaluated in cultured polyp epithelial cells and bronchial
      epithelial cells (BECs) in the presence of proinflammatory cytokines,
      corticosteroids and SPDEF small interfering RNA (siRNA) using qRT-PCR and western
      blot analysis. RESULTS: We found significantly increased SPDEF and MUC5AC
      expression in CRSwNP patients compared to the controls (P < .05); the mRNA level
      of SPDEF was positively correlated with MUC5AC expression in CRS patients (P <
      .05). There was a significant difference in SPDEF and MUC5AC expression in
      eosinophilic and noneosinophilic CRSwNP patients (P < .05). Interleukin (IL)-13,
      IL-8, and IL-17A significantly increased SPDEF and MUC5AC expression in vitro (P
      < .05). SPDEF siRNA significantly inhibited SPDEF and MUC5AC expression in BECs
      in response to IL-13, IL-8, and IL-17A (P < .05). CONCLUSIONS: Our findings
      suggested that SPDEF may be regarded as a promising therapeutic target for
      modulating mucus hypersecretion in CRSwNP.

PMID- 25376948
TI  - Fabrication of Advanced Functional Devices Combining Soft Chemistry with X-ray
      Lithography in One Step.
AB  - Deep X-ray lithography combined with sol-gel techniques offers facile fabrication
      of controlled patterned films. Using sol-gel, different functional properties can
      be induced; deep X-ray lithography alters the functionality in the exposed
      regions. Miniaturized devices based on local property changes are easily
      fabricated: this technique requires no resist, enabling direct patterning of
      films in a one-step lithographic process. 

PMID- 25376950
TI  - EPR study of the relationship between ultra high molecular weight polyethylene
      structure and radicals formed during irradiation with high energy sources.
AB  - Three different samples of ultra high molecular weight polyethylene have been
      irradiated with a high energy source (electron beam), and radicals have been
      generated. Different radical species have been assigned on the basis of their
      electron paramagnetic resonance spectra. Electron paramagnetic resonance data
      have been used also to evaluate the amount of each kind of radical that has been
      generated on different starting materials. The structure of the polymer (number
      of double bonds or crystallinity) is strictly connected to the response of the
      sample itself to the irradiation. A rationalization between these different
      parameters has been performed in order to evaluate the stability of polymer
      samples toward high energy irradiation processes.

PMID- 25376949
TI  - Ultrahigh-performance liquid chromatography and mass spectrometry (UHPLC
      LTQ/Orbitrap/MS/MS) study of phenolic profile of Serbian poplar type propolis.
AB  - INTRODUCTION: Propolis is a resinous natural substance collected by honeybees
      from different plant sources. Due to the presence of various phytochemicals, this
      bee-product exhibits numerous biological activities, including anti-bacterial,
      anti-viral, anti-inflammatory, anti-oxidant, immunostimulating and anti-tumour
      effects. As the chemical composition and biological activity of propolis depend
      on its botanical and geographical origin, searching for new bioactive substances
      in various types of propolis from unexplored regions is of great importance.
      OBJECTIVE: The aim of this study is the evaluation of the phenolic profile of
      poplar propolis samples in order to characterise Serbian propolis, to identify
      possible new constituents and to specify the phenolic components relevant for
      differentiation of poplar propolis samples into two subgroups through
      simultaneous analysis of poplar bud extracts. METHODS: Ethanolic extracts of
      propolis and poplar buds were comprehensively analysed using ultrahigh
      performance liquid chromatography coupled with hybrid mass spectrometry, which
      combines the linear trap quadrupole and Orbitrap MS/MS mass analyser together
      with chemometric methods. RESULTS: Extensive fingerprint analysis of Serbian
      propolis was achieved for the first time. Seventy-five phenolic compounds were
      detected. Eight of them were identified in propolis for the first time. Pattern
      recognition methods applied to the content of ten quantified phenolics verified
      the existence of two subgroups of propolis, with galangin, chrysin and
      pinocembrin as the most influential distinguishing factors. CONCLUSION: The
      phenolic composition of the analysed propolis samples confirm their affiliation
      to the European poplar type propolis and the existence of two subgroups according
      to botanical origin.

PMID- 25376951
TI  - Force for ancient and recent life: viral and stem-loop RNA consortia promote
      life.
AB  - Lytic viruses were thought to kill the most numerous host (i.e., kill the
      winner). But persisting viruses/defectives can also protect against viruses,
      especially in a ubiquitous virosphere. In 1991, Yarmolinsky et al. discovered the
      addiction modules of P1 phage, in which opposing toxic and protective functions
      stabilize persistence. Subsequently, I proposed that lytic and persisting cryptic
      virus also provide addiction modules that promote group identity. In eukaryotes
      (and the RNA world), a distinct RNA virus-host relationship exists.
      Retrovirurses/retroposons are major contributors to eukaryotic genomes.
      Eukaryotic complexity appears to be mostly mediated by regulatory complexity
      involving noncoding retroposon-derived RNA. RNA viruses evolve via quasispecies,
      which contain cooperating, minority, and even opposing RNA types. Quasispecies
      can also demonstrate group preclusion (e.g., hepatitis C). Stem-loop RNA domains
      are found in long terminal repeats (and viral RNA) and mediate viral
      regulation/identity. Thus, stem-loop RNAs may be ancestral regulators. I consider
      the RNA (ribozyme) world scenario from the perspective of addiction modules and
      cooperating quasispecies (i.e., subfunctional agents that establish group
      identity). Such an RNA collective resembles a "gang" but requires the
      simultaneous emergence of endonuclease, ligase, cooperative catalysis, group
      identity, and history markers (RNA). I call such a collective a gangen (pathway
      to gang) needed for life to emerge.

PMID- 25376952
TI  - Early main group metal catalysis: how important is the metal?
AB  - Organocalcium compounds have been reported as efficient catalysts for various
      alkene transformations. In contrast to transition metal catalysis, the alkenes
      are not activated by metal-alkene orbital interactions. Instead it is proposed
      that alkene activation proceeds through an electrostatic interaction with a Lewis
      acidic Ca(2+) . The role of the metal was evaluated by a study using the metal
      free catalysts: [Ph2 N(-) ][Me4 N(+) ] and [Ph3 C(-) ][Me4 N(+) ]. These "naked"
      amides and carbanions can act as catalysts in the conversion of activated double
      bonds (C?O and C?N) in the hydroamination of Ar?N?C?O and R?N?C?N?R (R=alkyl) by
      Ph2 NH. For the intramolecular hydroamination of unactivated C?C bonds in H2
      C?CHCH2 CPh2 CH2 NH2 the presence of a metal cation is crucial. A new type of
      hybrid catalyst consisting of a strong organic Schwesinger base and a simple
      metal salt can act as catalyst for the intramolecular alkene hydroamination. The
      influence of the cation in catalysis is further evaluated by a DFT study. 

PMID- 25376953
TI  - Respective contributions of Arabidopsis DCL2 and DCL4 to RNA silencing.
AB  - Dicer proteins are central to the different mechanisms involving RNA
      interference. Plants have evolved multiple DICER-LIKE (DCL) copies, thus enabling
      functional diversification. In Arabidopsis, DCL2 and DCL4 process double-stranded
      RNA into 22 and 21 nucleotide small interfering (si)RNAs, respectively, and have
      overlapping functions with regards to virus and transgene silencing. Nonetheless,
      some studies have reported that dcl2 or dcl4 single mutations are sometimes
      sufficient to hinder silencing. To better dissect the role of DCL2 and DCL4, we
      analyzed silencing kinetics and efficiencies using different transgenic systems
      in single and double mutant backgrounds. The results indicate that DCL2
      stimulates transitivity and secondary siRNA production through DCL4 while being
      sufficient for silencing on its own. Notably, silencing of 35S-driven transgenes
      functions more efficiently in dcl4 mutants, indicating that DCL4 mostly obscures
      DCL2 in wild-type plants. Nonetheless, in a dcl4 mutant compromised in phloem
      originating silencing, ectopically expressed DCL2 allows restoration of
      silencing, suggesting that DCL2 is not, or poorly, expressed in phloem.
      Remarkably, this ectopic DCL2 contribution to phloem-originating silencing is
      dependent on the activity of RNA-DEPENDENT RNA POLYMERASE6. These results
      indicate that, despite differences in the silencing activity of their small RNA
      products, DCL2 and DCL4 mostly act redundantly yet hierarchically when present
      simultaneously. 

PMID- 25376954
TI  - Rheumatologic rehabilitation: towards recommendations.
AB  - Rheumatic patients are highly complex and often affected by chronic diseases.
      Rehabilitation is generally needed for proper management of the underlying
      disease. This article describes the characteristics of an effective rheumatologic
      rehabilitation, takes into account data published in international literature,
      suggests recommendations based on scientific evidence to develop a correct
      rehabilitation plan for rheumatic patients and proposes the basis to draw up
      guidelines in the field of rheumatologic rehabilitation. 

PMID- 25376955
TI  - Predictive factors for partial remission according to the Ankylosing Spondylitis
      Assessment Study working group in patients with ankylosing spondylitis treated
      with anti-TNFalpha drugs.
AB  - The objective of this study was to evaluate the predictive factors for achieving
      partial remission (PR) in patients with ankylosing spondylitis (AS) treated with
      anti-TNFalpha. We longitudinally enrolled in a multi-center study 214 AS
      patients, classified according to New York criteria, treated with anti-TNFalpha
      drugs adalimumab (ADA), etanercept (ETA) and infliximab (INF) with at least 12
      months of follow up. PR was reached when the score was <20 mm (on a visual
      analogue scale of 0-100 mm) in each of the following 4 domains: 1) patient global
      assessment (in the last week); 2) pain (spinal pain); 3) function [measured by
      the bath ankylosing spondylitis functional index (BASFI)]; 4) inflammation [mean
      of intensity and duration of morning stiffness, from the bath ankylosing
      spondylitis disease activity index (BASDAI)]. Two hundred fourteen AS patients
      (M/F=160/54; median age/range=43.2/19-78 years; median disease duration/
      range=96/36-189 months) were treated with ADA (15.8%), ETA (28.9%) and INF
      (55.1%). At 12 and 24 months, high serum level of C reactive protein (CRP) (>=2
      vs <=0.8 mg/dL) were associated with higher rate of PR in AS patients treated
      with anti-TNFalpha drugs. At 24 months, PR was associated with shorter disease
      duration (<=36 vs >=189 months) and higher erythrosedimentation rate (ESR) values
      (>=45 vs <=17 mm/h). In male patients lower bath ankylosing spondylitis metrology
      index (BASMI) (<=2 vs >=6) and absence of psoriasis were associated with higher
      PR rate only at 12 months. Other parameters assessed before treatment, such as
      BASDAI, BASFI, peripheral arthritis, inflammatory bowel disease and uveitis were
      not associated with PR. Our long-term longitudinal study in a setting of clinical
      practice showed that inflammatory parameters (i.e. CRP, ESR) and disease duration
      represent the most important predictive variables to achieve PR with an anti
      TNFalpha treatment. 

PMID- 25376956
TI  - Possible interplay between interleukin-15 and interleukin-17 into the
      pathogenesis of idiopathic inflammatory myopathies.
AB  - The aim of this study was to assess the serum levels of interleukin (IL)-15 and
      IL-17 in patients with idiopathic inflammatory myopathies (IIM) and correlate
      them with IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1), macrophage
      inflammatory protein-1alpha (MIP-1alpha), MIP-1beta levels. Possible correlations
      with disease activity parameters were also evaluated. Sera from 14 polymyositis
      (PM), 10 dermatomyositis (DM), 7 anti-synthetase syndrome new onset patients and
      19 healthy controls (HCs) were analyzed by multiplex immunoassay. Sera from 19
      patients were analyzed after 5 months median follow-up. All patients underwent
      physical examination, the 5-points manual muscle test (MMT), the health
      assessment questionnaire and serum creatine kinase measurement. All patients
      received glucocorticoids, and 13 were taking also immunosuppressive therapy. At
      baseline, serum levels of IL-15, IL-17, MCP-1 and MIP-1beta were significantly
      higher in IIM patients than in HCs. IL-17 serum levels were directly correlated
      with disease duration (r=0.39, P=0.02), while a significant inverse correlation
      was detected between IL-17 levels and MMT scores (r=-0.4, P=0.02). The highest IL
      15 levels were present in DM patients (P=0.02 vs PM). The most striking finding
      was the strong correlation between IL-15 and IL-17 levels (r=0.60, P=0.0001), and
      this correlation was even stronger in DM patients (r=0.82, P=0.006). The strong
      correlation between IL-15 and IL-17 in IIM patients, and especially in DM,
      suggests that there may be a interplay between the two cytokines in the
      pathogenesis of myositis. Further studies of larger patient cohorts and muscle
      biopsies are needed to confirm these preliminary data. 

PMID- 25376957
TI  - Safety of rituximab in the routine treatment of rheumatoid arthritis in Italy in
      patients refractory to anti-TNFa drugs: results from the observational
      retrospective-prospective RUBINO study.
AB  - The paper reports the results from the observational retrospective-prospective
      RUBINO study conducted in Italy to assess the safety of rituximab in the
      treatment of rheumatoid arthritis (RA) in routine clinical practice. The
      percentage of patients who manifested at least one grade 3 or 4 adverse event
      (AE) assessed by the Common Terminology Criteria for Adverse Events version 3.0
      (CTCAE v.3) during the observation period (primary objective) was evaluated. The
      percentage of patients manifesting a severe AE (SAE), clinical response to
      rituximab treatment, clinical remission according to disease activity score for
      28 joints (DAS28) criteria, markers of disease and quality of life were also
      assessed. Fifty-three Italian rheumatology centers took part in the study.
      Patients with a diagnosis of RA and inadequate response to anti-tumor necrosis
      factor b (anti-TNFa) drugs were enrolled. Participating patients had previously
      received at least one cycle of rituximab, and treatment was still ongoing at the
      time of recruitment. Out of 205 patients enrolled, 60% manifested no form of AE,
      14.2% had at least one grade 3 or 4 AE, and 11.2% patients reported an SAE. The
      overall percentage of patients manifesting AEs (40%) was lower compared to the
      DANCER (81% and 85%), REFLEX (85%) and RESET (85% and 69%) studies, but higher
      than that observed in the CERERRA registry (from 10.2% to 13.9%). This difference
      may be due to the shorter observation period applied in the CERERRA registry
      (only 12 months) compared to the RUBINO study (up to 3 years). All parameters of
      RA activity (erythrocyte sedimentation rate, C-reactive protein, health
      assessment questionnaire score, DAS28) improved significantly during the study. 

PMID- 25376958
TI  - Radiologists and rheumatologists on performing and reporting shoulder ultrasound:
      from disagreement to consensus.
AB  - Shoulder pain is a common condition in the rheumatologist's practice, yet there
      are no guidelines on how to report shoulder ultrasound (US) examinations. The aim
      of this study was to compare scanning and reporting techniques performed by
      radiologists and rheumatologists and identify any discrepancies between the two.
      The participants in this study were five rheumatologists and two radiologists
      specialized in musculoskeletal US. The study was divided in 2 phases. In the
      first phase, each participant performed an US of 3 patients and reported the
      findings without knowing the patient diagnosis and the findings reported by the
      other operators. Other three investigators reported the US technique of each
      operator. Reports and images were subsequently compared to identify any
      discrepancies and reach consensus on a common approach. In the second phase, a US
      scan was performed on a fourth patient in a plenary session to assess feasibility
      and efficacy of the common approach The US scanning technique was similar for all
      operators. The differences in reporting emerged in the description of the rotator
      cuff disease. Radiologists provided a detailed description of lesions
      (measurements along 2 axis and scoring of lesions), whereas rheumatologists
      described carefully the inflammatory changes. The experts concluded that lesions
      should be measured along 2 axes and the grade of degeneration and the age of the
      lesion should be reported. Another difference emerged in the description of the
      irregularities of the bone surface. The experts concluded that the term erosion
      should be used only when an inflammatory joint disease is suspected. This study
      led to the clarification of some inconsistencies in US reporting, and represented
      an interesting collaborative experience between radiologists and rheumatologists.

PMID- 25376959
TI  - Superior oblique tendon (Brown's) syndrome as the presenting finding in childhood
      onset HLA-B27-related enthesitis and juvenile idiopathic oligoarticular
      arthritis.
AB  - We report two patients who presented with Brown's syndrome. The first is a 7-year
      old boy who at the time of his diagnosis was also found to have enthesitis and
      HLA-B27 positivity. The second patient was diagnosed with bilateral Brown's
      syndrome at 13 months of age. At age 7 she developed a persistent oligoarticular
      arthritis and unilateral anterior iritis consistent with the oligoarticular
      Juvenile Idiopatic Arthritis (JIA) phenotype. These cases highlight
      ophthalmologic findings and diagnostic considerations with respect to Brown's
      syndrome and associated childhood onset rheumatologic disease. 

PMID- 25376960
TI  - Perivascular fibrosis and IgG4-related disease: a case report.
AB  - Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized
      fibroinflammatory condition which can potentially involve any organ. Some
      characteristic histopathologic features with lymphoplasmacytic infiltrate, an
      increased number of IgG4+ cells, storiform fibrosis and obliterative phlebitis
      are the mainstay for diagnosis. Serum IgG4 levels often increase. We report the
      case of a patient with perivascular fibrotic lesions involving the aortic arch
      and the splenic hilum, with a surgical biopsy-proven diagnosis of IgG4-related
      disease. The patient is now undergoing a low-dose corticosteroid maintenance
      therapy without evidence of new localizations of the disease. This case
      highlights the need for increasing awareness and recognition of this new,
      emerging clinical condition. 

PMID- 25376961
TI  - Bilateral ptosis as a presenting feature of primary hypertrophic osteoarthropathy
      (pachydermoperiostosis): a case report.
AB  - Pachydermoperiostosis is a rare hereditary disorder, which affects both bones and
      skin. It is characterized by a combination of dermatologic changes (pachydermia
      or thickening of the skin) and rheumatologic manifestations (periostosis and
      finger clubbing). Eyelid ptosis which is caused by thickened eyelids
      (blepharoptosis) is a less common symptom. We report the case of a patient with a
      complete form of pachydermoperiostosis with bilateral ptosis as presenting
      feature. 

PMID- 25376962
TI  - Three-dimensional morphological condylar and mandibular changes in a patient with
      juvenile idiopathic arthritis: interdisciplinary treatment.
AB  - Temporomandibular joint (TMJ) involvement is common but usually delayed in
      patients with juvenile idiopathic arthritis (JIA). We describe the case of a JIA
      patient with bilateral TMJ involvement, mandibular retrognathia, bone erosion,
      and severely restricted mouth opening. The use of cone beam computed tomography
      and a 3D diagnostic protocol in young patients with JIA provides reliable,
      accurate and precise quantitative data and images of the condylar structures and
      their dimensional relationships. Analgesics and conventional disease modifying
      antirheumatic drugs were ineffective, but interdisciplinary treatment with
      etanercept and a Herbst functional appliance improved functional TMJ movement and
      bone resorption. 

PMID- 25376963
TI  - THE COGNITIVE COMPETENCES OF IMMIGRANT AND NATIVE STUDENTS ACROSS THE WORLD: AN
      ANALYSIS OF GAPS, POSSIBLE CAUSES AND IMPACT.
AB  - Immigration, immigration policies and education of immigrants alter competence
      levels. This study analysed their effects using PISA, TIMSS and PIRLS data (1995
      to 2012, N=93 nations) for natives' and immigrants' competences, competence gaps
      and their population proportions. The mean gap is equivalent to 4.71 IQ points.
      There are large differences across countries in these gaps ranging from around
      +12 to -10 IQ points. Migrants' proportions grow roughly 4% per decade. The
      largest immigrant-based 'brain gains' are observed for Arabian oil-based
      economies, and the largest 'brain losses' for Central Europe. Regarding causes of
      native-immigrant gaps, language problems do not seem to explain them. However,
      English-speaking countries show an advantage. Acculturation within one generation
      and intermarriage usually reduce native-immigrant gaps (?1 IQ point). National
      educational quality reduces gaps, especially school enrolment at a young age, the
      use of tests and school autonomy. A one standard deviation increase in school
      quality represents a closing of around 1 IQ point in the native-immigrant gap. A
      new Greenwich IQ estimation based on UK natives' cognitive ability mean is
      recommended. An analysis of the first adult OECD study PIAAC revealed that larger
      proportions of immigrants among adults reduce average competence levels and
      positive Flynn effects. The effects on economic development and suggestions for
      immigration and educational policy are discussed. 

PMID- 25376964
TI  - Metabolic syndrome in mental health and addiction treatment: a quantitative
      study.
AB  - ACCESSIBLE SUMMARY: Patients with mental illnesses have been found to shorter
      life expectancy due to an increased risk of heart disease. Some medication used
      to treat mental illnesses have been linked to weight gain and other physical
      change that make patients susceptible to heart disease. In order to reduce this
      risk it is important that health professionals regularly measure and monitor
      signs of these physical changes. This research has found that measuring both
      waist circumference and blood pressure of patients is a safe and reliable way to
      way to monitor patients. To identify if combined blood pressure and waist
      circumference measurements are reliable predictor of metabolic syndrome, a
      descriptive correlational design was used to examine the sensitivity and
      specificity of screening techniques used to detect metabolic syndrome. Data were
      collected regarding waist circumference, body mass index, blood pressure, fasting
      blood glucose, triglycerides and high-density lipoproteins. Blood pressure and
      waist circumference measurements demonstrated high significance, sensitivity and
      specificity as screening instruments for metabolic syndrome. Combined waist
      circumference and blood pressure measurements may be clinically useful for a
      quick and reliable detection of metabolic syndrome in patients with addiction and
      comorbid mental health problems.

PMID- 25376965
TI  - Concentrations of DDE in blubber biopsies of free-ranging long-beaked common
      dolphin (Delphinus capensis) in the Gulf of California.
AB  - Long-beaked common dolphins (Delphinus capensis) in the Gulf of California have
      been exposed to persistent contaminants that originated in large agricultural
      areas near the coast. Live common dolphins were sampled by remote dart biopsies
      to determine concentrations of tDDT in blubber. Life stage and initial gender
      identification was determined by field observations. Gender was confirmed by
      genetic analysis of the skin. Concentration of tDDT in blubber was analyzed by
      gas chromatography. The 16 samples collected consisted of: 2 adult males, 6 adult
      females, and 8 juveniles. 4,4'-DDE was detected in most of the samples with 4,4'
      DDD and 4,4'-DDT under detection levels. Concentrations of DDE varied from non
      detectable to 87.3 ug/g lipid weight with a median of 16 ug/g lipid weight. The
      highest concentration was detected in an immature female. No differences were
      detected between gender or life stage but this could be attributed to small
      sample size. We recommend continued sampling of D. capensis blubber biopsies from
      the Gulf of California in order to relate these levels with affected in vitro
      biomarkers such as mixed function oxidase activity.

PMID- 25376966
TI  - Tolerance of Portulaca grandiflora to individual and combined application of Ni,
      Pb and Zn.
AB  - In the present study, metal accumulation capacity and tolerance of Portulaca
      grandiflora were investigated. Plants were grown under greenhouse conditions in
      pots on soil amended with Ni, Pb and Zn to the final concentration of 2 mmol kg(
      1) for each metal. Results show considerable accumulating capacity and
      translocation of Ni and Zn, as well as significant accumulation of Pb in roots. A
      slight decrease of biomass with Zn and of chlorophyll content with Zn and Ni were
      observed, as well as an increase of proline content with each of the metals.
      Combinations of metals revealed mutual interference affecting both the uptake and
      translocation of the metals and their impact on physiological parameters. Results
      suggest that Portulaca grandiflora, although not a hyperaccumulator, shows a good
      tolerance and accumulation capacity for Ni, Pb and Zn, but, for the purposes of
      remediation, interference of the metals must be taken into account.

PMID- 25376967
TI  - Critical evaluation of the scientific content in clinical practice guidelines.
AB  - BACKGROUND: Increasing pressures to provide high-quality evidence-based cancer
      care have driven the rapid proliferation of clinical practice guidelines (CPGs).
      The quality and validity of CPGs have been questioned, and adherence to
      guidelines is relatively low. The purpose of this study was to critically
      evaluate the development process and scientific content of CPGs. METHODS: CPGs
      addressing management of rectal cancer were evaluated. We quantitatively assessed
      guideline quality with the validated Appraisal of Guidelines Research &
      Evaluation (AGREE II) instrument. We identified 21 independent processes of care
      using the nominal group technique. We then compared the evidence base and
      scientific agreement for the management recommendations for these processes of
      care. RESULTS: The quality and content of rectal cancer CPGs varied widely. Mean
      overall AGREE II scores ranged from 27% to 90%. Across the 5 CPGs, average scores
      were highest for the clarity of presentation domain (85%; range, 58% to 99%) and
      lowest for the applicability domain (21%; range, 8% to 56%). Randomized
      controlled trials represented a small proportion of citations (median, 18%;
      range, 13%-35%), 78% of the recommendations were based on low- or moderate
      quality evidence, and the CPGs only had 11 references in common with the highest
      rated CPG. There were conflicting recommendations for 13 of the 21 care processes
      assessed (62%). CONCLUSIONS: There is significant variation in CPG development
      processes and scientific content. With conflicting recommendations between CPGs,
      there is no reliable resource to guide high-quality evidence-based cancer care.
      The quality and consistency of CPGs are in need of improvement.

PMID- 25376968
TI  - Feeling an outsider left in uncertainty - a phenomenological study on the
      experiences of older hospital patients.
AB  - This paper starts from a care ethical perspective on care and reports on a
      phenomenological study into older patients' experiences of hospitalisation.
      Although hospital care for older patients is at the centre of attention,
      questions what is at stake and what defines quality of care are rarely discussed
      with a view to the perspective of older patients themselves. The qualitative
      observational method of shadowing was used. Ten patients of 75 years old or older
      were shadowed from admission until discharge. The reflective lifeworld approach,
      based on phenomenological philosophy, was used to analyse the collected data. For
      the older patients included in the study, the essential meaning of
      hospitalisation can be described as feeling an outsider left in uncertainty. The
      word 'left' reveals how hospitalisation is experienced as a solitary struggle
      with various uncertainties that are related both to the hospital environment and
      to the patient's personal situation. The essential meaning is composed of the
      following three constituents: (i) staying in an inhospitable place, (ii) feeling
      constrained and (iii) experiencing disruption. The busy walking back and forth of
      care professionals and the functional character of involvement, restrain older
      patients from participating and make them feel abandoned. Feeling constrained
      reveals the feelings brought on by the ageing body which are emphasised by
      hospitalisation but often neglected by hospital staff. The failure of healthcare
      professionals to recognise and respond to who older patients are aside from their
      illness exacerbate the experience of disruptions. To improve care, hospital staff
      must be more sensitive to older patients' uncertainties. Also, hospital staff
      should provide older patients with understandable information and explanation
      which besides offering patients the possibility to feel involved, meets their
      need for recognition.

PMID- 25376969
TI  - The effect of preeclampsia on the skin to subarachnoid distance in spinal
      anesthesia.
AB  - BACKGROUND: Preeclampsia is characterized by increased extracellular fluid which
      manifests as generalized edema due to endothelial injury and subsequent capillary
      leak. Therefore, preeclampsia may lead to increased skin to subarachnoid distance
      (SSD) which may influence daily clinical practice in this particular gravid
      population. METHODS: Age- and height-matched gravidas with and without
      preeclampsia were enrolled prospectively at an allocation ratio of 1:4. Spinal
      anesthesia (SA) was performed in a sitting position by a mid-line approach at the
      L3-L4 interspace using a 25-gauge Quincke spinal needle. An internal pilot study
      was performed to determine the sample size. When the protocol violations were
      excluded, 146 gravidas were included in the study (25 preeclamptics and 121
      normotensive controls) for final analysis. RESULTS: On average, SSD was 0.89 cm
      greater in preeclamptics compared to normotensive controls. Mean values of the
      SSD in preeclamptic and normotensive control group patients at the L3-L4
      interspace were 6.187 +/- 0.967 and 5.301 +/- 0.834 cm, respectively. SSD was
      significantly correlated with body weight and body mass index (BMI). The
      regression formula for the estimation of SSD in preeclamptic gravidas with BMI
      during SA was SSD = 3.696 + 0.075*BMI. The regression formula for the estimation
      of SSD in the normotensive control group with BMI during SA was SSD = 3.144 +
      0.067*BMI - 0.0001*BMI*BMI. CONCLUSION: Knowing that the SSD is increased in
      preeclamptics compared to normotensive gravidas may be of value in terms of
      selecting needle, and providing safe and comfortable anesthesia.

PMID- 25376970
TI  - Effects of dexmedetomidine on insulin secretion from rat pancreatic beta cells.
AB  - PURPOSE: Dexmedetomidine acts as a selective alpha2-adrenergic receptor agonist
      and an imidazoline receptor agonist, both of which are known to affect insulin
      secretion. Here, we investigated the effects of clinically relevant
      concentrations of dexmedetomidine on insulin secretion under in vivo conditions.
      Furthermore, its underlying mechanisms were examined using isolated islets in
      vitro. METHODS: For the in vivo oral glucose tolerance test (OGTT), male Sprague
      Dawley rats were randomly allocated to one of three groups (n = 7 in each group):
      two groups infused with dexmedetomidine at a low (group L) or a high (group H)
      dose, and one control group infused with the same amount of saline (group C). For
      the in vitro perifusion study, insulin released from isolated islets was measured
      during stepwise changes in glucose. Dexmedetomidine (0.1-100 uM) was added to the
      chamber. RESULTS: During the OGTT test, the insulin levels in group H were
      significantly lower than those in group C at 30, 60, and 90 min after glucose
      load. On the other hand, insulin levels in group L were comparable to those of
      group C at all time points. In the perfusion study, dexmedetomidine inhibited
      glucose-stimulated insulin secretion in a concentration-dependent manner. When co
      treated with yohimbine, an alpha2-adrenoceptor blocker, dexmedetomidine adversely
      increased glucose-induced insulin secretion. However, co-treatment with idazoxan,
      an antagonist for alpha2-adrenergic and imidazoline receptors, completely
      abolished the action of dexmedetomidine. CONCLUSIONS: Dexmedetomidine had no
      effect on insulin secretion at sedative dose, whereas it significantly inhibited
      insulin secretion at supraclinical high concentrations mainly via the alpha2
      adrenoceptor.

PMID- 25376971
TI  - Pectoral nerves I and II blocks in multimodal analgesia for breast cancer
      surgery: a randomized clinical trial.
AB  - BACKGROUND: The pectoral nerves (Pecs) block types I and II are novel techniques
      to block the pectoral, intercostobrachial, third to sixth intercostals, and the
      long thoracic nerves. They may provide good analgesia during and after breast
      surgery. Our study aimed to compare prospectively the quality of analgesia after
      modified radical mastectomy surgery using general anesthesia and Pecs blocks
      versus general anesthesia alone. METHODS: One hundred twenty adult female
      patients scheduled for elective unilateral modified radical mastectomy under
      general anesthesia were randomly allocated to receive either general anesthesia
      plus Pecs block (Pecs group, n = 60) or general anesthesia alone (control group,
      n = 60). RESULTS: Statistically significant lower visual analog scale pain scores
      were observed in the Pecs group than in the control group patients. Moreover,
      postoperative morphine consumption in the Pecs group was lower in the first 12
      hours after surgery than in the control group. In addition, statistically
      significant lower intraoperative fentanyl consumption was observed in the Pecs
      group than in the control group. In the postanesthesia care unit, nausea and
      vomiting as well as sedation scores were lower in the Pecs group compared with
      the control group. Overall, postanesthesia care unit and hospital stays were
      shorter in the Pecs group than in the control group. CONCLUSIONS: The combined
      Pecs I and II block is a simple, easy-to-learn technique that produces good
      analgesia for radical breast surgery.

PMID- 25376973
TI  - Evidence Base for the Use of Ultrasound for Upper Extremity Blocks: 2014 Update.
AB  - This article reviews and summarizes randomized, controlled studies that have
      assessed ultrasound (US) guidance for brachial plexus blocks in comparison with
      other nerve localization methods as well as those that have compared different US
      guided brachial plexus block techniques. Both PubMed and EMBASE databases were
      searched using the MeSH terms anesthetic technique, brachial plexus, and
      ultrasound. Studies were included if they had randomized allocation comparing US
      with another conventional nerve localization technique or if they compared 2
      different US-guided techniques, such as single versus multiple injections. Each
      study was classified as a categorical outcome as being supportive, unclear, or
      negative for the use of US. These were compared with chi analysis with the null
      hypothesis that US provides no benefit for brachial plexus blocks. Forty-seven
      studies met the inclusion criteria, and 29 compared US guidance to landmark or
      peripheral nerve stimulation techniques. Our analysis of the literature supports
      the use of US over other nerve localization techniques as being beneficial for
      several block performance outcomes including block performance time, reducing the
      number of needle passes and the incidence of vascular puncture, shortening
      sensory block onset time, and improving block success. 

PMID- 25376972
TI  - Effect of adductor canal block versus femoral nerve block on quadriceps strength,
      mobilization, and pain after total knee arthroplasty: a randomized, blinded
      study.
AB  - BACKGROUND AND OBJECTIVES: Total knee arthroplasty (TKA) is often associated with
      severe pain. Different regional anesthetic techniques exist, all with varying
      degrees of motor blockade. We hypothesized that pain relief provided by the
      adductor canal block (ACB) could increase functional muscle strength. METHODS: We
      included 50 TKA patients with severe movement-related pain; defined as having
      visual analog scale pain score of greater than 60 mm during active flexion of the
      knee. The ACB group received an ACB with ropivacaine 0.2% 30 mL and a femoral
      nerve block (FNB) with 30 mL saline. The FNB group received an ACB with 30 mL
      saline and an FNB with ropivacaine 0.2% 30 mL. We compared the effect of the ACB
      versus FNB on maximum voluntary isometric contraction of the quadriceps muscle
      relative to a postoperative baseline value. Secondary end points were differences
      between groups in ability to ambulate and changes in pain scores
      (Clinicaltrials.gov identifier NCT01922596). RESULTS: After block, the quadriceps
      maximum voluntary isometric contraction increased to 193% (95% confidence
      interval [CI], 143-288) of the baseline value in the ACB group and decreased to
      16% (95% CI, 3-33) in the FNB group with an estimated difference of 178% (95% CI,
      136-226), P < 0.0001. Pain scores were similar between groups. Before block, 2 of
      25 patients in each group were unable to perform the Timed-Up-and-Go test; after
      block, this number increased to 7 of 25 in the FNB group and decreased to 0 of 25
      in the ACB group. CONCLUSION: Adductor canal block provides a clinically relevant
      and statistically significant increase in quadriceps muscle strength for patients
      in severe pain after TKA.

PMID- 25376975
TI  - Nonaqueous Li-air batteries: a status report.

PMID- 25376974
TI  - Genetic, molecular and clinical determinants for the involvement of aldosterone
      and its receptors in major depression.
AB  - Major depression (MDE) has metabolic and neuroendocrine correlates, which point
      to a biological overlap between MDE and cardiovascular diseases. Whereas the
      hypothalamic-pituitary-adrenocortical axis has long been recognized for its
      involvement in depression, the focus was mostly on cortisol/corticosterone,
      whereas aldosterone appears to be the 'forgotten' stress hormone. Part of the
      reason for this is that the receptors for aldosterone, the mineralocorticoid
      receptors (MR), were thought to be occupied by glucocorticoids in most parts of
      the brain. However, recently it turned out that aldosterone acts selectively in
      relevant mood-regulating brain areas, without competing with
      cortisol/corticosterone. These areas include the nucleus of the solitary tract
      (NTS), the amygdala and the paraventricular nucleus of the hypothalamus. These
      regions are intimately involved in the close relationship between emotional and
      vegetative symptoms. Genetic analysis supports the role of aldosterone and of MR
      related pathways in the pathophysiology of depression. Functional markers for
      these pathways in animal models as well as in humans are available and allow an
      indirect assessment of NTS function. They include heart rate variability,
      baroreceptor reflex sensitivity, blood pressure, salt taste sensitivity and slow
      wave sleep. MR activation in the periphery is related to electrolyte regulation.
      MR overactivity is a risk factor for diabetes mellitus and a trigger of
      inflammatory processes. These markers can be used not only to assist the
      development of new treatment compounds, but also for a personalized approach to
      treat patients with depression and related disorders by individual dose titration
      with an active medication, which targets this system.

PMID- 25376976
TI  - Risk of bleeding related to selective and non-selective serotonergic
      antidepressants: a case/non-case approach using data from two pharmacovigilance
      databases.
AB  - INTRODUCTION: There is increasing evidence for an association between treatment
      with selective serotonin reuptake inhibitors (SSRI) and an increased risk of
      bleeding events. The most important underlying mechanism appears to be inhibition
      of serotonin uptake in platelets, an effect that is also present in
      antidepressants with non-selective serotonin-reuptake inhibition (NSRI).
      Accordingly, also NSRI may be associated with an increased risk of bleeding.
      However, there is little data in this regard. METHODS: Based on data (spontaneous
      reports of adverse drug reactions) from 2 pharmacovigilance databases (WHO
      database/VigibaseTM; BfArM/AkdA-database in Germany) we used a case/non-case
      approach and calculated reporting odds ratios (ROR) as measures for
      disproportionality regarding the association of treatment with an agent of the
      group SSRI/NSRI and haemorrhages. RESULTS: Whereas both positive control agents
      (ASS and diclofenac) were statistically associated with haemorrhages in both
      databases (ASS: BfArM/AkdA, ROR 13.62 [95% CI 12.76-14.53]/WHO, ROR 12.96 [95% CI
      12.75-13.16]; diclofenac: BfArM/AkdA, ROR 3.01 [95% CI 2.71-3.21]/WHO, ROR 2.11
      [95% CI 2.05-2.16]), none of the agents of the group SSRI (ROR<1) was associated
      with haemorrhages. In group NSRI, only St. John's wort/hypericum was associated
      with haemorrhages (WHO-database, ROR 1.31 [95% CI 1.06-1.63]). DISCUSSION: Signal
      detectioning in 2 pharmacovigilance databases suggest that serotonin reuptake
      inhibition is not associated with an increased risk of bleeding. However,
      underreporting may have accounted for the evaluated absent associations,
      particularly concerning SSRI. Regarding the detected increased risk of bleeding
      associated with hypericum, pharmacokinetic drug-drug interactions may be relevant
      independent of serotonin reuptake inhibition.

PMID- 25376977
TI  - "Schizophrenia past clozapine": reasons for clozapine discontinuation, mortality,
      and alternative antipsychotic prescribing.
AB  - INTRODUCTION: The clinical records of 190 patients with schizophrenia who
      discontinued clozapine between 1990 and 2012 in the county of Northamptonshire
      were examined, in an attempt to answer the following questions. Why do patients
      stop clozapine? What do physicians prescribe as an alternative? What is the
      mortality in this patient group? METHODS: Patients' data were extracted using
      their electronic records, then analysed using descriptive statistical methods.
      RESULTS: Non-compliance with treatment, or with the mandatory white blood cell
      monitoring, was the most common reason (55.3%) for clozapine cessation, followed
      by neutropaenia and other adverse effects (25.2%). Death (mean age 48 years) was
      the third most common reason (10%), with respiratory infections accounting for
      more than a quarter of the deaths. 13% of the patients had died (mean age 49
      years) at some point following clozapine discontinuation. In terms of the
      alternative antipsychotic prescribing, olanzapine was the most commonly
      prescribed (37.1%) drug in patients who were still under the care of the local
      psychiatric service (n=121), at the time of data extraction. Clozapine had been
      reinstated in 19% of these patients. DISCUSSION: Our findings are generally
      consistent with previous studies, and they demonstrate the need for physicians to
      address their patients' concerns regarding clozapine treatment, and to
      effectively manage any adverse effects. Sialorrhea and constipation seem to be
      particularly of concern, as they may be linked to clozapine- related mortality.
      Olanzapine was the most commonly prescribed alternative to clozapine, which
      suggests that it may possibly have a role in refractory schizophrenia.

PMID- 25376978
TI  - Thermodiffusion, molecular diffusion and Soret coefficient of binary and ternary
      mixtures of n-hexane, n-dodecane and toluene.
AB  - In this study, the thermodiffusion, molecular diffusion, and Soret coefficients
      of 12 binary mixtures composed of toluene, n-hexane and n-dodecane in the whole
      range of concentrations at atmospheric pressure and temperatures of 298.15 K and
      308.15 K have been determined. The experimental measurements have been carried
      out using the Thermogravitational Column, the Sliding Symmetric Tubes and the
      Thermal Diffusion Forced Rayleigh Scattering techniques. The results obtained
      using the different techniques show a maximum deviation of 9% for the
      thermodiffusion coefficient, 8% for the molecular diffusion coefficient and 2%
      for the Soret coefficient. For the first time we report a decrease of the
      thermodiffusion coefficient with increasing ratio of the thermal expansion
      coefficient and viscosity for a binary mixture of an organic ring compound with a
      short n-alkane. This observation is discussed in terms of interactions between
      the different components. Additionally, the thermogravitational technique has
      been used to measure the thermodiffusion coefficients of four ternary mixtures
      consisting of toluene, n-hexane and n-dodecane at 298.15 K. In order to complete
      the study, the values obtained for the molecular diffusion coefficient in binary
      mixtures, and the thermodiffusion coefficient of binary and ternary mixtures have
      been compared with recently derived correlations. 

PMID- 25376979
TI  - Transition experience of young adults with inflammatory bowel diseases (IBD): a
      mixed methods study.
AB  - BACKGROUND: Outcomes following transition can be poor; many young adults are ill
      prepared to take responsibility for their health care, older adolescents report
      incomplete understanding of medications, and parents remain largely responsible
      for their care. Good patient-provider relationships are associated with better
      adherence; however, the role of the relationship between post-transition patients
      and their providers has not been explored. The current study aimed to understand
      transition of young adults with inflammatory bowel diseases (IBD), the impact of
      the paediatric patient-provider relationship and what determines the adult
      patient-provider relationship. METHODS: This study examined the experience of
      young adults with Crohn's disease or ulcerative colitis (aged 18-30) after
      transition. Twenty-nine patients completed a 31-item online survey of their
      transition experience from paediatric to adult care. Responses were coded
      quantitatively and qualitatively, and qualitative responses were analysed by two
      independent raters. RESULTS: Positive themes regarding adult providers included
      independence, autonomy and trust, while negative themes included initial
      discomfort and confusing logistics. Five of six patients who reported
      'terrifying' first visit experiences with their adult providers reported overall
      positive relationships. The earlier the diagnosis age, the less involved in
      medical decisions they were as an adult (r = 0.41, P = .03). Those who had a more
      positive experience with their paediatric providers were more likely to bring up
      confusion with their adult providers (r = .45, P = .04), and those who had a more
      positive experience with their adult providers were more likely to endorse
      collaborative medical decision-making (r = .57, P < .001). CONCLUSIONS: Patients
      diagnosed with IBD at a young age may need extra education and self-management
      strategies, as they were less likely to exhibit behaviours indicative of a
      successful transition to adult care. Additionally, transition programme
      development may benefit from the post-transition perspective across chronic
      illness populations.

PMID- 25376980
TI  - A series of cobalt and nickel clusters based on thiol-containing ligands
      accompanied by in situ ligand formation.
AB  - Eight cobalt and nickel clusters with the formulae [Co4(MU4-O)(MBT)5(MU2-Piv)]
      (1), [Ni3(MBT)2(L1)2(OCH3)2] (2), [Ni4(MU3-S)(MU3-S2)(MBT)2(L2)] (3), [Ni4(L3)4]
      (4), [Ni6(MU4-S)3(MBT)6].(C2H5OH)2 (5), H[Co4(MU4
      O)(HMBI)6].(NO3)(TEA)0.5(CH3OH)2(H2O) (6), [Ni2(HMBI)4].(CH3OH)2 (7), and
      [Ni5(MBI)2(HMBI)4(OCH3)2].(CH3OH)3(H2O)2 (8) (HPiv = pivalic acid, HL1 = 2
      disulfanylbenzo[d]thiazole, H2L2 = (Z)-2-((2
      mercaptophenyl)imino)benzo[d]thiazole-3(2H)-thiol, H2L3 = (Z)-2-(benzo[d]thiazol
      2(3H)-ylideneamino)benzenethiol, TEA = triethylamine) have been solvothermally
      prepared via assembling distinct metal resource and thiol-containing ligands 2
      mercaptobenzothiazole (HMBT)/2-mercaptobenzimidazole (H2MBI). Complexes 1 and 6
      are tetrahedral cobalt clusters. Complex 2 features linear arrangement of nickel
      ions. Complexes 3 and 4 are tetranuclear nickel clusters with the butterfly and
      square shape, respectively. Complex 5 displays a trigonal prism geometry.
      Complexes 7 and 8 exhibit paddle-wheel and trigonal bipyramidal geometry,
      respectively. The starting ligand HMBT undergoes in situ ligand transformation in
      the formation of the nickel clusters, and the new generated inorganic ligands
      (S(2-) and S2(2-)) and organic ligands (HL1, H2L2 and H2L3) were captured within
      the metallic cores. Magnetic studies indicate that complexes 1 and 6 show
      dominating antiferromagnetic couplings and that spin frustration exists in 6. 

PMID- 25376981
TI  - Alpha-fetoprotein: A biomarker for the recruitment of progenitor cells in the
      liver in patients with acute liver injury or failure.
AB  - AIM: The optimal conditions for hepatocyte proliferation should be clarified in
      an attempt to improve the impaired liver regeneration observed in patients with
      acute liver failure (ALF). In order to evaluate the significance of the serum
      alpha-fetoprotein (AFP). level and prothrombin time international normalized
      ratio (PT-INR) as possible biomarkers of the proliferation of liver
      stem/progenitor cells (LPC) and mature hepatocytes (MH), respectively, we focused
      on donors of living donor liver transplantation (LDLT) and patients with acute
      liver injury (ALI), including ALF. METHODS: Seventy-three patients with ALI/ALF
      and 11 donors for LDLT were evaluated. LPC induction was histologically evaluated
      using cytokeratin (CK)-7 staining in 45 ALI/ALF patients. RESULTS: The AFP level
      was not apparently elevated during the observation period in any of the LDLT
      donors, whereas the serum AFP levels were substantially increased in the patients
      with ALI/ALF and significantly correlated with the number of CK-7 positive LPC in
      the liver, except for very severe damaged liver. All patients exhibiting an early
      peak in the AFP level prior to PT-INR elevation died. CONCLUSION: The serum AFP
      level may reflect the induction of LPC in ALI/ALF patients. The substantial and
      persistent induction of LPC until sufficient regeneration of MH may be needed for
      a recovery from ALF. We herein demonstrate that the serum AFP level may be a
      serum marker of LPC in patients with ALI/ALF. A comparison of the serial changes
      in the AFP levels and PT-INR in our study patients showed impaired proliferation
      of LPC and delayed recovery of MH in the patients who died.

PMID- 25376982
TI  - Acneiform rash: an unusual presentation of epithelioid haemangioma.

PMID- 25376983
TI  - Best anthropometric and atherogenic predictors of metabolic syndrome in the
      Chinese Han population in Xinjiang: the Cardiovascular Risk Survey.
AB  - OBJECTIVE: This study aimed to identify the best predictor of metabolic syndrome
      (MetS) by comparing the predicting ability of various anthropometric and
      atherogenic parameters in the Chinese Han population in Xinjiang. METHODS: A
      representative, cross-sectional sample of 5,757 Chinese Han adults were selected
      from the Cardiovascular Risk Survey conducted from October 2007 to March 2010.
      MetS prevalence, area under the curve (AUC), distance on the receiver operating
      characteristic curve and the cut-offs of each variable were compared for the
      presence of MetS. RESULTS: According to the criteria of the International
      Diabetes Federation (IDF), the Joint Interim Statement (JIS) and the Third Adult
      Treatment Panel (ATPIII), 32.1, 48.5, 39.3% of men and 38.0, 45.1, 44.9% of women
      had MetS in Xinjiang. According to the IDF criteria, the waist-to-height ratio
      (WHtR) had the highest AUC value in men (0.836) and women (0.837), with the
      optimal cut-off of 0.54 in men and 0.53 in women. According to both the JIS and
      ATPIII criteria, triglycerides/high-density lipoprotein cholesterol TG/HDL-C had
      the highest AUC value in men (0.830 and 0.833, respectively) and women (0.832 and
      0.827, respectively), with the optimal cut-offs being 1.6 and 1.2 in men and 1.1
      and 1.1 in women, respectively. CONCLUSION: WHtR was the best predictor of MetS
      according to the IDF criteria while TG/HDL-C was the best predictor of MetS
      according to the JIS and ATPIII criteria.

PMID- 25376984
TI  - Associations between ghrelin and ghrelin receptor polymorphisms and cancer in
      Caucasian populations: a meta-analysis.
AB  - BACKGROUND: There is growing evidence that the ghrelin axis, including ghrelin
      (GHRL) and its receptor, the growth hormone secretagogue receptor (GHSR), play a
      role in cancer progression. Ghrelin gene and ghrelin receptor gene polymorphisms
      have been reported to have a range of effects in cancer, from increased risk, to
      protection from cancer, or having no association. In this study we aimed to
      clarify the role of ghrelin and ghrelin receptor polymorphisms in cancer by
      performing a meta-analysis of published case-control studies. RESULTS: In the
      overall analysis, homozygous and recessive associations indicated that the minor
      alleles of rs696217 and rs2075356 GHRL polymorphisms conferred reduced cancer
      risk (odds ratio [OR] 0.61-0.78). The risk was unchanged for breast cancer
      patients when analysed separately (OR 0.73-0.83). In contrast, the rs4684677 GHRL
      and the rs572169 GHSR polymorphisms conferred increased breast cancer risk (OR
      1.97-1.98, p = 0.08 and OR 1.42-1.43, p = 0.08, respectively). All dominant and
      co-dominant effects showed null effects (OR 0.96-1.05), except for the rs572169
      co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05).
      CONCLUSIONS: This study suggests that the rs696217 and rs2075356 ghrelin gene
      (GHRL) polymorphisms may protect carriers against breast cancer, and the
      rs4684677 GHRL and rs572169 GHSR polymorphisms may increase the risk among
      carriers. In addition, larger studies are required to confirm these findings.

PMID- 25376985
TI  - Accuracy of a computed tomography bronchial wall thickness to pulmonary artery
      diameter ratio for assessing bronchial wall thickening in dogs.
AB  - Computed tomography is increasingly being used in veterinary medicine to evaluate
      animals with pulmonary signs such as coughing, tachypnea, and exercise
      intolerance, however, a quantitative measure of bronchial wall thickening has yet
      to be validated in veterinary medicine. Canine chronic bronchitis is a disease
      that is characterized histologically by thickening of the bronchial walls.
      Thoracic CT images of 16 dogs with chronic bronchitis and 72 dogs presenting for
      conditions unrelated to cough were evaluated. A ratio comparing the bronchial
      wall thickness to the adjacent pulmonary artery diameter was obtained in the
      right and left cranial and caudal lung lobes. There was no significant difference
      in dogs with chronic bronchitis or unaffected dogs between the left and right
      hemithorax, patient weight, patient age, image slice thickness, or CT machine
      used. Dogs with chronic bronchitis were found to have a significantly greater
      ratio than unaffected dogs (P < 0.001). The ratios in the cranial lung lobes were
      found to be significantly greater than the caudal lung lobes in both chronic
      bronchitis and unaffected dogs (P < 0.001). A receiver operating characteristic
      curve of the ratios in the cranial lung lobes had an area under the curve of
      0.912, indicating high accuracy in predicting for bronchial wall thickening. A
      ratio of >= 0.6 in the cranial lung lobes was found to have a sensitivity of 77%
      and specificity of 100% in predicting for the presence of chronic bronchitis, and
      we propose using this cut-off as supportive of bronchial wall thickening on CT.

PMID- 25376986
TI  - Influence of gestational age on dead space and alveolar ventilation in preterm
      infants ventilated with volume guarantee.
AB  - BACKGROUND: Ventilated preterm infant lungs are vulnerable to overdistension and
      underinflation. The optimal ventilator-delivered tidal volume (VT) in these
      infants is unknown and may depend on the extent of alveolarisation at birth.
      OBJECTIVES: We aimed to calculate respiratory dead space (VD) from the molar mass
      (MM) signal of an ultrasonic flowmeter (VD,MM) in very preterm infants on volume
      targeted ventilation (VT target, 4-5 ml/kg) and to study the association between
      gestational age (GA) and VD,MM-to-VT ratio (VD,MM/VT), alveolar tidal volume (VA)
      and alveolar minute volume (AMV). METHODS: This was a single-centre, prospective,
      observational, cohort study in a neonatal intensive care unit. Tidal breathing
      analysis was performed in ventilated very preterm infants (GA range 23-32 weeks)
      on day 1 of life. RESULTS: Valid measurements were obtained in 43/51 (87%)
      infants. Tidal breathing variables were analysed using multivariable linear
      regression. VD,MM/VT was negatively associated with GA after adjusting for birth
      weight Z score (p < 0.001, R(2) = 0.26). This association was primarily
      influenced by the appliance dead space. Despite similar VT/kg and VA/kg across
      all studied infants, respiratory rate and AMV/kg increased with GA. CONCLUSIONS:
      VD,app rather than anatomical VD is the major factor influencing increased
      VD,MM/VT at a younger GA. A volume guarantee setting of 4-5 ml/kg in the Drager
      Babylog(r) 8000 plus ventilator may be inappropriate as a universal target across
      the GA range of 23-32 weeks. Differences between measured and set VT and the
      dependence of this difference on GA require further investigation.

PMID- 25376988
TI  - n-type chalcogenides by ion implantation.
AB  - Carrier-type reversal to enable the formation of semiconductor p-n junctions is a
      prerequisite for many electronic applications. Chalcogenide glasses are p-type
      semiconductors and their applications have been limited by the extraordinary
      difficulty in obtaining n-type conductivity. The ability to form chalcogenide
      glass p-n junctions could improve the performance of phase-change memory and
      thermoelectric devices and allow the direct electronic control of nonlinear
      optical devices. Previously, carrier-type reversal has been restricted to the
      GeCh (Ch=S, Se, Te) family of glasses, with very high Bi or Pb 'doping'
      concentrations (~5-11 at.%), incorporated during high-temperature glass melting.
      Here we report the first n-type doping of chalcogenide glasses by ion
      implantation of Bi into GeTe and GaLaSO amorphous films, demonstrating
      rectification and photocurrent in a Bi-implanted GaLaSO device. The electrical
      doping effect of Bi is observed at a 100 times lower concentration than for Bi
      melt-doped GeCh glasses. 

PMID- 25376987
TI  - Murine precision-cut liver slices (PCLS): a new tool for studying tumor
      microenvironments and cell signaling ex vivo.
AB  - BACKGROUND: One of the most insidious characteristics of cancer is its spread to
      and ability to compromise distant organs via the complex process of metastasis.
      Communication between cancer cells and organ-resident cells via
      cytokines/chemokines and direct cell-cell contacts are key steps for survival,
      proliferation and invasion of metastasized cancer cells in organs. Precision-cut
      liver slices (PCLS) are considered to closely reflect the in vivo situation and
      are potentially useful for studying the interaction of cancer cells with liver
      resident cells as well as being a potentially useful tool for screening anti
      cancer reagents. Application of the PCLS technique in the field of cancer
      research however, has not yet been well developed. RESULTS: We established the
      mouse PCLS system using perfluorodecalin (PFD) as an artificial oxygen carrier.
      Using this system we show that the adherence of green fluorescent protein (GFP)
      labeled MDA-MB-231 (highly invasive) cells to liver tissue in the PCLS was 5-fold
      greater than that of SK-BR-3 (less invasive) cells. In addition, we generated
      PCLS from THOC5, a member of transcription/export complex (TREX), knockout (KO)
      mice. The PCLS still expressed Gapdh or Albumin mRNAs at normal levels, while
      several chemokine/growth factor or metalloprotease genes, such as Cxcl12, Pdgfa,
      Tgfb, Wnt11, and Mmp1a genes were downregulated more than 2-fold. Interestingly,
      adhesion of cancer cells to THOC5 KO liver slices was far less (greater than 80%
      reduction) than to wild-type liver slices. CONCLUSION: Mouse PCLS cultures in the
      presence of PFD may serve as a useful tool for screening local adherence and
      invasiveness of individual cancer cells, since single cells can be observed. This
      method may also prove useful for identification of genes in liver-resident cells
      that support cancer invasion by using PCLS from transgenic liver.

PMID- 25376989
TI  - Detection beyond Debye's length with an electrolyte-gated organic field-effect
      transistor.
AB  - Electrolyte-gated organic field-effect transistors are successfully used as
      biosensors to detect binding events occurring at distances from the transistor
      electronic channel that are much larger than the Debye length in highly
      concentrated solutions. The sensing mechanism is mainly capacitive and is due to
      the formation of Donnan's equilibria within the protein layer, leading to an
      extra capacitance (CDON) in series to the gating system.

PMID- 25376991
TI  - Introduction to the special issue on the Second Australian Study of Health and
      Relationships.

PMID- 25376992
TI  - Design and methods of the Second Australian Study of Health and Relationships.
AB  - Background This paper describes the methods and process of the Second Australian
      Study of Health and Relationships. METHODS: A representative sample of the
      Australian population was contacted by landline and mobile phone modified random
      digit dialling in 2012-13. Computer-assisted telephone interviews elicited
      sociodemographic and health details as well as sexual behaviour and attitudes.
      For analysis, the sample was weighted to reflect the study design and further
      weighted to reflect the location, age and sex distribution of the population at
      the 2011 Census. RESULTS: Interviews were completed with 9963 men and 10131 women
      aged 16-69 years from all states and territories. The overall participation rate
      among eligible people was 66.2% (63.9% for landline men, 67.9% for landline women
      and 66.5% for mobile respondents). Accounting for the survey design and adjusting
      to match the 2011 Census resulted in a weighted sample of 20094 people (10056 men
      and 10038 women). The sample was broadly representative of the Australian
      population, although as in most surveys, people with higher education and higher
      status occupations were over-represented. Data quality was high, with the great
      majority saying they were not at all or only slightly embarrassed by the
      questionnaire and almost all saying they were 90-100% honest in their answers.
      CONCLUSIONS: The combination of methods and design in the Second Australian Study
      of Health and Relationships, together with the high participation rate, strongly
      suggests that the results of the study are robust and broadly representative of
      the Australian population.

PMID- 25376993
TI  - Attitudes toward sex and relationships: the Second Australian Study of Health and
      Relationships.
AB  - Background Attitudes towards sex and relationships influence laws about what is
      and is not permissible and social sanctions against behaviours considered
      unacceptable. They are an important focus for research given their links to
      sexual behaviour. The aim of the present study was to describe attitudes towards
      sex and relationships, to identify correlates of scores on a scale of sexual
      liberalism and to examine responses to jealousy-evoking scenarios among
      Australian adults. METHODS: Computer-assisted landline and mobile telephone
      interviews were completed by a population-representative sample of 20094 men and
      women aged 16-69 years. The overall participation rate among eligible people was
      66.2%. Respondents expressed their agreement with 11 attitude statements, five of
      which formed a valid scale of liberalism, and also responded to a jealousy
      evoking scenario. RESULTS: There was general agreement that premarital sex was
      acceptable (87%), that sex was important for wellbeing (83%) and that sex outside
      a committed relationship was unacceptable (83%). Respondents were accepting of
      homosexual behaviour and abortion and few believed that sex education encouraged
      earlier sexual activity. More liberal attitudes were associated with: being
      female; speaking English at home; homosexual or bisexual identity; not being
      religious; greater education; and higher incomes. Respondents who expressed more
      liberal attitudes had more diverse patterns of sexual experience. Predicted sex
      differences were found in response to the jealousy-evoking scenario - men were
      more jealous of a partner having sex with someone else and women were more
      jealous of a partner forming an emotional attachment - but responses varied with
      age. CONCLUSION: Sexual attitudes of Australians largely support a permissive but
      monogamous paradigm. Since 2002, there has been a shift to less tolerance of sex
      outside a committed relationship, but greater acceptance of homosexual behaviour.

PMID- 25376990
TI  - Global discovery of protein kinases and other nucleotide-binding proteins by mass
      spectrometry.
AB  - Nucleotide-binding proteins, such as protein kinases, ATPases and GTP-binding
      proteins, are among the most important families of proteins that are involved in
      a number of pivotal cellular processes. However, global study of the structure,
      function, and expression level of nucleotide-binding proteins as well as protein
      nucleotide interactions can hardly be achieved with the use of conventional
      approaches owing to enormous diversity of the nucleotide-binding protein family.
      Recent advances in mass spectrometry (MS) instrumentation, coupled with a variety
      of nucleotide-binding protein enrichment methods, rendered MS-based proteomics a
      powerful tool for the comprehensive characterizations of the nucleotide-binding
      proteome, especially the kinome. Here, we review the recent developments in the
      use of mass spectrometry, together with general and widely used affinity
      enrichment approaches, for the proteome-wide capture, identification and
      quantification of nucleotide-binding proteins, including protein kinases,
      ATPases, GTPases, and other nucleotide-binding proteins. The working principles,
      advantages, and limitations of each enrichment platform in identifying nucleotide
      binding proteins as well as profiling protein-nucleotide interactions are
      summarized. The perspectives in developing novel MS-based nucleotide-binding
      protein detection platform are also discussed. (c) 2014 Wiley Periodicals, Inc.
      Mass Spec Rev 35:601-619, 2016.

PMID- 25376994
TI  - First vaginal intercourse and oral sex among a representative sample of
      Australian adults: the Second Australian Study of Health and Relationships.
AB  - Background Current information about the characteristics of Australian adults'
      first vaginal intercourse and contraception or precautions used on that occasion
      is needed, as well as whether these characteristics have changed between 2001-02
      and 2012-13. METHODS: Computer-assisted telephone interviews were completed by a
      representative sample of 20094 men and women aged 16-69 years. The overall
      participation rate among eligible people was 66.2%. Respondents indicated their
      age at first vaginal intercourse and first oral sex. Those who reported vaginal
      intercourse were asked the age of their partner, their relationship to their
      partner, the duration of this relationship, and what contraception or precautions
      (if any) were used. RESULTS: There was a significant decline in the median age of
      first vaginal intercourse for both men and women among those born between the
      1940s and the 1960s, but no further decline since. There has also been a
      significant increase in the use of protection at first vaginal intercourse, from
      less than 20% of men and women in the 1950s to over 90% in the 2000s. For men and
      women, first vaginal sex before age 16 years was significantly associated with a
      greater number of lifetime and recent sexual partners, and a greater likelihood
      of having had a sexually transmitted infection. CONCLUSION: Given the earlier age
      at first vaginal intercourse, sex education should begin earlier so that all
      young people have information about contraception and disease prevention before
      they begin their sexual careers.

PMID- 25376995
TI  - Heterosexual experience and recent heterosexual encounters among Australian
      adults: the Second Australian Study of Health and Relationships.
AB  - Background Current information about numbers of other-sex partners, experiences
      of different heterosexual behaviours and the recent heterosexual experiences
      among a representative sample of Australian adults is needed. It is not known
      whether these practices have changed between 2001-02 and 2012-13. METHODS:
      Computer-assisted telephone interviews were completed by a representative sample
      of 9963 men and 10131 women aged 16-69 years from all states and territories. The
      overall participation rate among eligible people was 66.2%. RESULTS: Men reported
      more sexual partners than women, although the lifetime number of heterosexual
      partners reported by women increased significantly between 2001-02 and 2012-13.
      In 2012-13, 14.7% of men and 8.6% of women reported two or more sexual partners
      in the last year. Reporting multiple partners was significantly associated with
      being younger, being bisexual, living in major cities, having a lower income,
      having a blue-collar occupation and not being married. The proportion of
      respondents reporting ever having had oral sex or anal intercourse increased
      significantly since the last survey. At the last heterosexual encounter, 91.9% of
      men and 66.2% of women had an orgasm, oral sex was reported in only approximately
      one in four encounters and anal intercourse was uncommon. CONCLUSION: There were
      increases between 2001-02 and 2012-13 in partner numbers among women and in the
      lifetime experience of oral and anal sex. The patterns of heterosexual experience
      in Australia are similar to those found in studies of representative samples in
      other countries.

PMID- 25376996
TI  - Characteristics of heterosexual regular relationships among a representative
      sample of adults: the Second Australian Study of Health and Relationships.
AB  - Background The aim of this study was to describe important characteristics of
      Australian adults' heterosexual regular sexual relationships and examine how
      these characteristics have changed since 2002. METHODS: Computer-assisted
      landline and mobile telephone interviews were completed by a representative
      sample of 20 094 Australian residents aged 16-69 years. The participation rate
      among eligible people was 66.2%. Data were collected on respondents' social and
      demographic characteristics, relationship status and duration, cohabitation
      status, partner's age, contraception use, expectations about sexual exclusivity,
      sexual partners in the previous year, actual and ideal frequencies of sex and
      levels of physical pleasure and emotional satisfaction in their relationships.
      RESULTS: Most sexually active respondents 89%; 74% of all respondents, were in a
      heterosexual regular relationship. Most (97%) expected sexual exclusivity in
      their relationships, with 3% reporting extradyadic sex in the previous year.
      Respondents reported an average frequency of sex of 1.44 times per week, with
      most reporting very high levels of physical pleasure (men, 88%; women, 76%) and
      emotional satisfaction (men, 86%; women, 84%) in their relationships. Comparisons
      with data from the First Australian Study of Health and Relationships revealed
      that significantly more sexually active men were in a relationship in the current
      survey; that respondents' average frequency of sex was significantly lower; and
      that women's reports of extreme emotional satisfaction had risen. Otherwise,
      results were consistent with those of the first study. CONCLUSIONS: In general,
      results suggested that the characteristics of Australians' heterosexual
      relationships changed little between 2002 and 2013. Despite a decline in
      respondents' average weekly frequency of sex, the majority of respondents
      reported being in a highly satisfying, sexually exclusive relationship.

PMID- 25376997
TI  - Homosexual experience and recent homosexual encounters: the Second Australian
      Study of Health and Relationships.
AB  - Background The aim of this study is to describe homosexual experience and
      characteristics of recent homosexual encounters among Australian adults and
      identify changes between 2001-02 and 2012-13. METHODS: Computer-assisted
      telephone interviews were completed by a representative sample of 20094 men and
      women aged 16-69 years and the participation rate among eligible people was
      66.2%. Respondents indicated the number of same-sex partners they had had in
      their lifetime and in the last 12 months. Those who reported any homosexual
      experience were asked the age at which this first occurred and about
      characteristics of the first and most recent homosexual encounter. RESULTS:
      Reporting ever having same-sex experience was more common in women (13.5%) than
      in men (6.5%, P<0.001). Among these people, men reported more lifetime and recent
      same-sex partners than women (P<0.001). Same-sex experience was associated with
      some but not all indices of higher socioeconomic status. In men, it was
      associated with living in a major city (P=0.02) and in women, it was associated
      with younger (<30 years) age and with very low income (P<0.001). Men were younger
      than women at their first homosexual encounter (P=0.005). Women were more likely
      than men to have their first same-sex encounter with a regular partner. For women
      but not men, there was a significant increase in the proportion reporting same
      sex experience since 2001-02. CONCLUSION: Same-sex experience is not uncommon and
      is increasing in prevalence in young Australian women. The high number of same
      sex partners among homosexual and bisexual men places them at greater risk of
      sexually transmissible infection.

PMID- 25376999
TI  - Masturbation, paying for sex, and other sexual activities: the Second Australian
      Study of Health and Relationships.
AB  - Background This study describes the prevalence of (solo) masturbation, paying for
      sex and a range of other sexual practices among Australians. METHODS: A
      representative sample of 20094 men and women aged 16-69 years (participation rate
      among eligible people, 66.2%) were recruited by landline and mobile phone random
      digit dialling and computer-assisted telephone interviews in 2012-13. RESULTS:
      Many respondents (men, 72%; women, 42%) had masturbated in the past year. Half
      (51%) of the men and 24% of women had masturbated in the past 4 weeks. In the
      past year, more than two-fifths of respondents (men, 63%; women, 20%) had looked
      at pornography in any medium. Approximately 15% of men and 21% of women had used
      a sex toy. Digital-anal stimulation with a partner was practised by 19% of men
      and 15% of women, and oral-anal stimulation by 7% of men and 4% of women. Sexual
      role playing or dressing up were engaged in by 7-8%. Online sex, swinging, group
      sex, BDSM (bondage and discipline, 'sadomasochism' or dominance and submission)
      and fisting (rectal or vaginal) were each engaged in by less than 3% of the
      sample. Seventeen per cent of men said they had ever paid for sex; 2% had done so
      in the past year. CONCLUSION: Most of the solo practices studied were engaged in
      by more men than women, but women were more likely to have used a sex toy.
      Autoerotic activities are both substitutes for partnered sex and additional
      sources of pleasure for people with sexual partners.

PMID- 25376998
TI  - Sexual identity, sexual attraction and sexual experience: the Second Australian
      Study of Health and Relationships.
AB  - Background Behavioural and other aspects of sexuality are not always consistent.
      This study describes the prevalence and overlap of same-sex and other-sex
      attraction and experience and of different sexual identities in Australia.
      METHODS: Computer-assisted telephone interviews were completed by a
      representative sample of 20094 men and women aged 16-69 years recruited by
      landline and mobile phone random-digit dialling with a response rate
      (participation rate among eligible people) of 66.2%. Respondents were asked about
      their sexual identity ('Do you think of yourself as' heterosexual/straight,
      homosexual/gay, bisexual, etc.) and the sex of people with whom they had ever had
      sexual contact and to whom they had felt sexually attracted. RESULTS: Men and
      women had different patterns of sexual identity. Although the majority of people
      identified as heterosexual (97% men, 96% women), women were more likely than men
      to identify as bisexual. Women were less likely than men to report exclusively
      other-sex or same-sex attraction and experience; 9% of men and 19% of women had
      some history of same-sex attraction and/or experience. Sexual attraction and
      experience did not necessarily correspond. Homosexual/gay identity was more
      common among men with tertiary education and living in cities and less common
      among men with blue-collar jobs. Many gay men (53%) and lesbians (76%) had some
      experience with an other-sex partner. More women identified as lesbian or
      bisexual than in 2001-02. Similarly, more women reported same-sex experience and
      same-sex attraction. CONCLUSION: In Australia, men are more likely than women to
      report exclusive same-sex attraction and experience, although women are more
      likely than men to report any non-heterosexual identity, experience and
      attraction. Whether this is a feature of the plasticity of female sexuality or
      due to lesser stigma than for men is unknown.

PMID- 25377000
TI  - Experiences of sexual coercion in a representative sample of adults: the Second
      Australian Study of Health and Relationships.
AB  - Background It is important to have current reliable estimates of the prevalence,
      correlates and consequences of sexual coercion among a representative sample of
      Australian adults and to identify changes over time in prevalence and
      consequences. METHODS: Computer-assisted telephone interviews were completed by a
      representative sample of 20094 Australian men and women aged 16-69 years. The
      participation rate among eligible people was 66.2%. RESULTS: Sexual coercion
      (i.e. being forced or frightened into sexual activity) was reported by 4.2% of
      men and 22.4% of women. Sexual coercion when aged <=16 years was reported by 2.0%
      of men and 11.5% of women. Correlates of sexual coercion were similar for men and
      women. Those who had been coerced reported greater psychosocial distress, were
      more likely to smoke, were more anxious about sex and more likely to have
      acquired a sexually transmissible infection. Few people had talked to others
      about their experiences of sexual coercion and fewer had talked to a
      professional. There were no significant differences between the First and Second
      Australian Study of Health and Relationships in whether men or women had
      experienced coercion, talked to anyone about this or talked to a counsellor or
      psychologist. CONCLUSION: Sexual coercion has detrimental effects on various
      aspects of people's lives. It usually occurs at the ages at which people become
      sexually active. There is a need to reduce the incidence of sexual coercion,
      better identify experiences of sexual coercion, and provide accessible services
      to minimise the detrimental effects of sexual coercion.

PMID- 25377001
TI  - Knowledge about and experience of sexually transmissible infections in a
      representative sample of adults: the Second Australian Study of Health and
      Relationships.
AB  - Background Sexually transmissible infections (STIs) present a substantial public
      health burden, and are related to modifiable sexual behaviours. METHODS: Computer
      assisted telephone interviews were completed by a population-representative
      sample of 20 094 men and women aged 16-69 years. The overall participation rate
      among eligible people was 66.2%. Respondents were asked questions regarding their
      knowledge about, self-reported history of, and testing for STIs. RESULTS: STI
      knowledge was better in women, the young, people of higher socioeconomic status,
      those with a variety of indicators of being at high STI risk and those with a
      history of receiving sex education in school. Approximately one in six men and
      women reported a lifetime history of an STI. A history of STI testing in the last
      year was reported by ~one in six (17%) women and one in eight men (13%) and
      higher rates of testing in women were reported in most high-risk groups. The
      highest rates of STI testing (61%) and HIV testing (89%) were reported in
      homosexual men. CONCLUSION: Knowledge of STI-related health consequences and
      transmission is improving in Australians, and rates of STI testing were
      relatively high but were higher in women than in men. Further increases in
      testing rates in both sexes will be required to facilitate the early diagnosis
      and treatment of STIs, which is a cornerstone of STI control.

PMID- 25377002
TI  - Safer sex and condom use: findings from the Second Australian Study of Health and
      Relationships.
AB  - Background It is important to have current and reliable estimates of the
      frequency and correlates of condom use among Australian adults. METHODS: A
      representative sample of 20094 men and women aged 16-69 years, from all states
      and territories, completed computer-assisted telephone interviews. The overall
      participation rate among eligible people was 66.2%. RESULTS: Although most
      respondents had used a condom at some time in their lives, fewer than half of
      those who were sexually active in the year before being interviewed had used a
      condom in that year. Condom use in the last year was associated with youth,
      speaking a language other than English at home, bisexual identity, greater
      education, residence in major cities, lower income and having multiple sexual
      partners in the last year. One-quarter of respondents used a condom the last time
      they had vaginal intercourse and one-sixth of these were put on after genital
      contact. Condom use during most recent vaginal sex was associated with youth,
      lower income, having sex with a non-regular partner and not using another form of
      contraception. Condom use appears to have increased between 2001-02 and 2012-13.
      CONCLUSION: Consistent with other research, this study showed that condom use was
      strongly associated with partner type and use of other contraception. There may
      be a need to highlight among people with multiple sexual partners the fact that
      non-barrier methods of contraception do not offer protection against sexually
      transmissible infections. The finding that many condoms were applied after
      genital contact suggests a need to promote both use and correct use of condoms.

PMID- 25377003
TI  - Change and stasis in sexual health and relationships: comparisons between the
      First and Second Australian Studies of Health and Relationships.

PMID- 25377005
TI  - Perceptions of Plagiarism by STEM Graduate Students: A Case Study.
AB  - Issues of academic integrity, specifically knowledge of, perceptions and
      attitudes toward plagiarism, are well documented in post-secondary settings using
      case studies for specific courses, recording discourse with focus groups,
      analyzing cross-cultural education philosophies, and reviewing the current
      literature. In this paper, the authors examine the perceptions of graduate
      students in science, technology, engineering, and mathematics (STEM) disciplines
      at the University of Florida regarding misconduct and integrity issues. Results
      revealed students' perceptions of the definition and seriousness of potential
      academic misconduct, knowledge of institutional procedures, and views on faculty
      actions, all with a focus on divergences between U.S. and internationally
      educated students. The open-ended questions provide anecdotal evidence to
      highlight personal experiences, positive and negative, aimed at the faculty,
      international students and undergraduates. Combined, these findings outline an
      important part of the campus academic integrity culture at a major American
      university. Recommendations for local actions also are discussed.

PMID- 25377006
TI  - Studies on the antioxidant activity of some chromonylrhodanine derivatives.
AB  - Fifteen chromonylrhodamine derivatives (CRs) were synthesized and the antioxidant
      activity levels were evaluated for the first time. The antioxidant activity
      potencies of these chromone derivatives were evaluated towards superoxide anion
      radicals, hydroxyl radicals and 2,2-diphenyl-1-picrylhydrazyl radicals. Also, the
      total antioxidant capacity of the tested compounds was measured using the ferric
      ferrozine assay. The antioxidant activities were investigated using a
      chemiluminescence (CL) assay, spectrophotometry measurements, direct electron
      paramagnetic resonance (EPR) and the EPR spin-trapping technique. The 5,5
      dimethyl- 1-pyrroline-1-oxide (DMPO) was applied as spin trap. Eleven of the 15
      chromone compounds exhibited a decrease in the CL accompanying the superoxide
      anion radical produced in anhydrous dimethylsulfoxide (DMSO), ranging from 71-94%
      at concentration of 1 mmol /L; four of these compounds enhanced light emission in
      the range 231-672%. Similarly, these compounds caused 28-58% inhibition in the
      intensity of the DMPO-OOH radical EPR signal and the DMPO-OH radical (from 12
      48%). Furthermore, three of these compounds showed very good antioxidant response
      towards the DPPH radical (EC50 : 0.51-0.56 umol/L) and the high reduction
      potentials. These findings demonstrate that the chromone compounds tested may be
      considered as effective free radicals scavengers, a finding that is of great
      pharmacological importance.

PMID- 25377007
TI  - The Kv1.1 null mouse, a model of sudden unexpected death in epilepsy (SUDEP).
AB  - OBJECTIVE: Kv1.1 potassium channel null mouse (NULL) exhibits spontaneous seizure
      related bradycardia, dies following seizure, and has been proposed as a model for
      vagus-mediated SUDEP. We characterized the cardiac events surrounding sudden
      unexpected death in epilepsy (SUDEP) in NULL during terminal asystole for
      comparison to patients with epilepsy who exhibit bradycardia and terminal or
      nonterminal asystole during/following seizure and explored the contribution of
      vagal-mediated bradycardia to SUDEP. METHODS: Electrocardiography (ECG) studies
      of 27 freely moving telemetered NULL mice was evaluated surrounding seizure
      associated death. Chronic unilateral vagal section and, in a separate set of
      experiments, electrical stimulation of the cervical vagi in NULL and wild-type
      (WT) littermates assessed the role of the vagus nerve in seizure-related death.
      Seizure activity indicated by intense myogenic activity on the ECG recording
      correlated with visual and video recording. RESULTS: All NULL died following
      seizures, which were preceded by normal rhythm. Bradycardia followed seizure and
      led to slow ventricular escape rhythm (70-150 bpm) and asystole. The sequence
      from seizure to asystole was complete within approximately 3 min and was similar
      to that reported in individuals exhibiting ictal and postictal
      bradycardia/asystole. To address the singular role of vagus nerves in seizure
      related asystole, cervical vagus nerves were stimulated in the absence of
      seizure. Heart rate was reduced 3 min to values similar to that following seizure
      but never produced asystole, suggesting activation of the vagi alone is
      insufficient for SUDEP. Nevertheless, unilateral chronic section of the vagus
      nerve increased survival time compared to nonsectioned NULL animals, supporting a
      role for the vagus nerve in seizure-associated death. SIGNIFICANCE: The Kv1.1
      null mouse is a potential model for SUDEP in patients who experience ictal and
      postictal bradycardia. It offers the opportunity for evaluation of the
      combination of factors, in addition to vagal activation, necessary to produce a
      terminal asystole following seizure. It is notable that long-term studies that
      evaluate electroencephalography (EEG) and cardiorespiratory events surrounding
      nonfatal seizures may provide indices predictive of terminal seizure.

PMID- 25377008
TI  - Case fatality rate and associated factors in patients with 22q11 microdeletion
      syndrome: a retrospective cohort study.
AB  - OBJECTIVE: Chromosome 22q11.2 deletion is the most commonly occurring known
      microdeletion syndrome. Deaths related to the syndrome have been reported, but
      the magnitude of death has not been quantified. This study evaluated the
      deletion's impact on survival and its clinical manifestations in a large cohort
      of Chilean patients. DESIGN: Demographic and clinical data of individuals with
      22q11 deletions diagnosed between 1998 and 2013 were collected from medical
      records and death certificates. Case fatality rate was calculated and compared
      with national vital statistics. OR with 95% CI analysis was used to assess the
      association between clinical manifestations and death. SETTING: Genetic services
      in tertiary care centres in Chile, following patients with 22q11.2 deletion.
      OUTCOMES: Fatality rate and associated factors. RESULTS: 59 of 419 patients
      (14.1%) died during the study period at a median of 3.4 months (range 0 to 32
      years of age). Factors associated with death included congenital heart disease
      (OR 5.27; 95% CI 2.06 to 13.99; p<0.0001), hypocalcaemia (OR 4.27; 95% CI 1.67 to
      11.15; p<0.002) and airway malacia (OR 13.37; 95% CI 1.19 to 110.51; p<0.002).
      Patients with deletions and defects such as tetralogy of Fallot with or without
      pulmonary atraesia, truncus arteriosus or ventricular septal defect, had a 2.6
      fold to 4.6-fold higher death rate compared with nationwide reports for the same
      types of defects. CONCLUSIONS: In this cohort, we observed a death rate of 14.1%,
      implying that one in seven patients with 22q11 deletion died during the study
      period. Significant associations with cardiac defects, hypocalcaemia and airway
      malacia were observed. Furthermore, the death risk in patients with 22q11
      deletion and cardiac defects exceeded the global figures observed in Chile for
      infants with structurally similar but apparently isolated anomalies. These
      observations indicate a need to identify patients who may require specific
      perioperative management to improve survival.

PMID- 25377009
TI  - Fruit and vegetable intake and risk of type 2 diabetes mellitus: meta-analysis of
      prospective cohort studies.
AB  - OBJECTIVE: To clarify and quantify the potential dose-response association
      between the intake of fruit and vegetables and risk of type 2 diabetes. DESIGN:
      Meta-analysis and systematic review of prospective cohort studies. DATA SOURCE:
      Studies published before February 2014 identified through electronic searches
      using PubMed and Embase. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective
      cohort studies with relative risks and 95% CIs for type 2 diabetes according to
      the intake of fruit, vegetables, or fruit and vegetables. RESULTS: A total of 10
      articles including 13 comparisons with 24,013 cases of type 2 diabetes and
      434,342 participants were included in the meta-analysis. Evidence of curve linear
      associations was seen between fruit and green leafy vegetables consumption and
      risk of type 2 diabetes (p=0.059 and p=0.036 for non-linearity, respectively).
      The summary relative risk of type 2 diabetes for an increase of 1 serving fruit
      consumed/day was 0.93 (95% CI 0.88 to 0.99) without heterogeneity among studies
      (p=0.477, I(2)=0%). For vegetables, the combined relative risk of type 2 diabetes
      for an increase of 1 serving consumed/day was 0.90 (95% CI 0.80 to 1.01) with
      moderate heterogeneity among studies (p=0.002, I(2)=66.5%). For green leafy
      vegetables, the summary relative risk of type 2 diabetes for an increase of 0.2
      serving consumed/day was 0.87 (95% CI 0.81 to 0.93) without heterogeneity among
      studies (p=0.496, I(2)=0%). The combined estimates showed no significant benefits
      of increasing the consumption of fruit and vegetables combined. CONCLUSIONS:
      Higher fruit or green leafy vegetables intake is associated with a significantly
      reduced risk of type 2 diabetes.

PMID- 25377010
TI  - Physician user satisfaction with an electronic medical records system in primary
      healthcare centres in Al Ain: a qualitative study.
AB  - OBJECTIVES: To explore physician satisfaction with an electronic medical records
      (EMR) system, to identify and explore the main limitations of the system and
      finally to submit recommendations to address these limitations. DESIGN: A
      descriptive qualitative study that entailed three focus group interviews was
      performed among physicians using open-ended questions. The interviews were
      audiotaped, documented and transcribed verbatim. The themes were explored and
      analysed in different categories. SETTING: The study was conducted in primary
      healthcare centres (PHC) in Al Ain, United Arab Emirates (UAE). PARTICIPANTS: A
      total of 23 physicians, all using the same EMR system, attended one of three
      focus groups held in PHC in Al Ain Medical District. Each focus group consisted
      of 7-9 physicians working in PHC as family medicine specialists, residents or
      general practitioners. PRIMARY OUTCOME MEASURE: Physician satisfaction with the
      EMR system. RESULTS: Key themes emerged and were categorised as physician
      dependent, patient-related and system-related factors. In general, physicians
      were satisfied with the EMR system in spite of initial difficulties with
      implementation. Most participants identified that the long time required to do
      the documentation affected their practice and patient communication. Many
      physicians expressed satisfaction with the orders and results of laboratory and
      radiology functions and they emphasised that this was the strongest point in the
      EMR. They were also satisfied with the electronic prescription function, stating
      that it reduced errors and saved time. CONCLUSIONS: Physicians are satisfied with
      the EMR and have a positive perception regarding the application of the system.
      Several themes emerged during this study that need to be considered to enhance
      the EMR system. Further studies need to be conducted among other healthcare
      practitioners and patients to explore their attitude and perception about the
      EMR.

PMID- 25377011
TI  - The association of statin use with reduced incidence of venous thromboembolism: a
      population-based cohort study.
AB  - OBJECTIVES: Venous thromboembolism (VTE) continues to be a frequent medical
      emergency requiring rapid recognition so as to reach diagnosis and initiate
      anticoagulation therapy. The use of statins in addition to reducing the incidence
      of arterial thrombosis for decreasing the incidence and reoccurrence of VTE is
      reported. The aim of our study was to explore the association between statin
      usage and the incidence of new VTE at the population level during a 10-year
      follow-up. DESIGN: Population-based historic cohort. SETTING: The Health 2000
      Survey was based on a nationally representative sample. PARTICIPANTS: 8028
      individuals aged 30 years or over in Finland. PRIMARY AND SECONDARY OUTCOME
      MEASURES: The primary end point event was the first ever hospitalisation due to
      one of the following causes: pulmonary embolism (International Classification of
      Diseases-10 I26), cerebral venous non-pyogenic thrombosis (I63.6), or venous
      thrombosis (I80.9-189). RESULTS: The preselected explanatory variables applied to
      the Poisson regression model were statin usage (no/yes) during follow-up (2000
      2011) and several baseline data (age, sex; usage of blood glucose lowering drugs,
      vitamin K antagonists and antiplatelet agents). We observed 136 VTE events, the
      incidence of 1.72 (95% CI 1.44 to 2.04) per 1000 person-years. Current statin
      usage did not associate with the incidence of VTE according to the univariate
      model (rate ratio (RR) 0.93, 0.56 to 1.52), but when adjusted with baseline
      variables (age, sex, medications) the RR declined to 0.60 (0.36 to 1.00, p=0.04).
      CONCLUSIONS: Statin use offers protection against first ever VTE events and
      appears as a primary prevention tool in patients without anticoagulation or
      antiplatelet medication.

PMID- 25377012
TI  - Objectively-assessed and self-reported sedentary time in relation to multiple
      socioeconomic status indicators among adults in England: a cross-sectional study.
AB  - OBJECTIVES: To examine the associations between socioeconomic position (SEP) and
      multidomain self-reported and objectively-assessed sedentary time (ST). DESIGN:
      Cross-sectional. SETTING: General population households in England. PARTICIPANTS:
      2289 adults aged 16-96 years who participated in the 2008 Health Survey for
      England. OUTCOMES: Accelerometer-measured ST, and self-reported television time,
      non-television leisure-time sitting and occupational sitting/standing. We
      examined multivariable associations between household income, social class,
      education, area deprivation for each SEP indicator (including a 5-point composite
      SEP score computed by aggregating individual SEP indicators) and each ST
      indicator using generalised linear models. RESULTS: Accelerometry-measured total
      ST and occupational sitting/standing were positively associated with SEP score
      and most of its constituent SEP indicators, while television time was negatively
      associated with SEP score and education level. Area-level deprivation was largely
      unrelated to ST. Those in the lowest composite SEP group spent 64 (95% CIs 52 to
      76) and 72 (48 to 98), fewer minutes/day in total ST and occupational
      sitting/standing compared to those in the top SEP group, and an additional 48 (35
      60) min/day watching television (p<0.001 for linear trend). Stratified analyses
      showed that these associations between composite SEP score and total ST were
      evident only among participants who were in employment. CONCLUSIONS: Occupational
      sitting seems to drive the positive association between SEP and total ST. Lower
      SEP is linked to higher TV viewing times.

PMID- 25377013
TI  - Evaluation of electronic prescription implementation in polymedicated users of
      Catalonia, Spain: a population-based longitudinal study.
AB  - OBJECTIVES: To assess whether electronic prescribing is a comprehensive health
      management tool that may contribute to rational drug use, particularly in
      polymedicated patients receiving 16 or more medications in the public healthcare
      system in the Barcelona Health Region (BHR). DESIGN: 16 months of retrospective
      study followed by 12 months of prospective monitoring. SETTING: Primary
      healthcare in BHR, Catalonia, Spain. PARTICIPANTS: All insured patients,
      especially those who are polymedicated in six basic health areas (BHA).
      Polymedicated patients were those with a consumption of >=16 drugs/month.
      INTERVENTIONS: Monitoring demographic and consumption variables obtained from the
      records of prescriptions dispensed in pharmacies and charged to the public health
      system, as well as the resulting drug use indicators. Territorial variables
      related to implementation of electronic prescribing were also described and were
      obtained from the institutional data related to the deployment of the project.
      MAIN OUTCOME MEASURES: Trend in drug use indicators (number of prescriptions per
      polymedicated user, total cost per polymedicated user and total cost per
      prescription) according to e-prescription implementation. RESULTS: There was a
      significant upward trend in the number of polymedicated users, number of
      prescriptions and total cost (p<0.05), which seemed independent from the
      implementation of electronic prescribing when comparing the preimplementation and
      postimplementation period. Prescriptions per user and cost per user showed a
      decrease between the preimplementation and postimplementation period, being
      significant in two BHAs (p<0.05). CONCLUSIONS: Results suggest that after the
      implementation of electronic prescribing, the rationality of prescribing in
      polymedicated patients improved. In addition, this study provides a very valuable
      approach for future impact assessment.

PMID- 25377014
TI  - Antibiotic prescribing in long-term care facilities: a qualitative,
      multidisciplinary investigation.
AB  - OBJECTIVES: To explore healthcare professionals' views of antibiotic prescribing
      in long-term care facilities (LTCFs). To use the findings to recommend
      intervention strategies for antimicrobial stewardship in LTCFs. DESIGN:
      Qualitative semistructured interviews were conducted. The data were analysed by
      thematic content analysis. After the interviews, the emerging findings were
      mapped to the theoretical domains framework (TDF), and the behaviour change wheel
      and behaviour change technique (BCT) taxonomy were used to recommend future
      intervention strategies. PARTICIPANTS: Interviews were conducted with 37
      healthcare professionals who work in LTCFs (10 general practitioners, 4
      consultants, 14 nurses, 9 pharmacists) between December 2012 and March 2013.
      SETTING: Interviews were conducted in the greater Cork region. RESULTS: The main
      domains from the TDF which emerged were: 'Knowledge', 'Environmental context and
      resources', 'Social influences', 'Beliefs about consequences', 'Memory, attention
      and decision making', with the findings identifying a need for 'Behavioural
      regulation'. Many participants believed that antibiotic prescribing was
      satisfactory at their LTCF, despite the lack of surveillance activities.
      CONCLUSIONS: This study, using the TDF and BCT taxonomy, has found that
      antibiotic prescribing in LTCFs is influenced by many social and contextual
      factors. The challenges of the setting and patient population, the belief about
      consequences to the patient, and the lack of implementation of guidelines and
      knowledge regarding antibiotic prescribing patterns are significant challenges to
      address. On the basis of the study findings and the application of the TDF and
      BCT taxonomy, we suggest some practical intervention functions for antimicrobial
      stewardship in LTCFs.

PMID- 25377015
TI  - Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a
      multicentre randomised study comparing indwelling pleural catheter versus talc
      pleurodesis.
AB  - INTRODUCTION: Malignant pleural effusion can complicate most cancers. It causes
      breathlessness and requires hospitalisation for invasive pleural drainages.
      Malignant effusions often herald advanced cancers and limited prognosis.
      Minimising time spent in hospital is of high priority to patients and their
      families. Various treatment strategies exist for the management of malignant
      effusions, though there is no consensus governing the best choice. Talc
      pleurodesis is the conventional management but requires hospitalisation (and
      substantial healthcare resources), can cause significant side effects, and has a
      suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory
      fluid drainage without hospitalisation, and are increasingly employed for
      management of malignant effusions. Previous studies have only investigated the
      length of hospital care immediately related to IPC insertion. Whether IPC
      management reduces time spent in hospital in the patients' remaining lifespan is
      unknown. A strategy of malignant effusion management that reduces hospital
      admission days will allow patients to spend more time outside hospital, reduce
      costs and save healthcare resources. METHODS AND ANALYSIS: The Australasian
      Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial
      designed to compare IPC with talc pleurodesis for the management of malignant
      pleural effusion. This study will randomise 146 adults with malignant pleural
      effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end
      point is the total number of days spent in hospital (for any admissions) from
      treatment procedure to death or end of study follow-up. Secondary end points
      include hospital days specific to pleural effusion management, adverse events,
      self-reported symptom and quality-of-life scores. ETHICS AND DISSEMINATION: The
      Sir Charles Gairdner Group Human Research Ethics Committee has approved the study
      as have the ethics boards of all the participating hospitals. The trial results
      will be published in peer-reviewed journals and presented at scientific
      conferences. TRIAL REGISTRATION NUMBERS: Australia New Zealand Clinical Trials
      Registry-ACTRN12611000567921; National Institutes of Health-NCT02045121.

PMID- 25377016
TI  - Pregnancy-related ICU admissions in France: trends in rate and severity, 2006
      2009.
AB  - OBJECTIVE: To determine the national rate per delivery of pregnancy-related ICU
      admissions of women in France, the characteristics and severity of these cases,
      and their trends over the 4-year study period. DESIGN: Descriptive study from the
      national hospital discharge database. SETTING: All ICUs in France. PATIENTS: All
      women admitted to an ICU during the pregnancy, the delivery, or the postpartum
      period from January 1, 2006, to December 31, 2009. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Of 3,262,526 deliveries, 11,824 women had
      pregnancy-related ICU admissions, for an overall rate of 3.6 per 1,000
      deliveries. The conditions reported most frequently were obstetric hemorrhages
      (34.2%) and hypertensive disorders of pregnancy (22.3%). Case severity was
      assessed with four markers: case-fatality rate (1.3%), length of ICU stay (mean,
      3.0 +/- 0.1 d), Simplified Acute Physiology Score II score (mean: 19.7 +/- 0.1),
      and a SUP REA code, which indicates the combination of a Simplified Acute
      Physiology Score II score more than or equal to 15 and at least one specific
      procedure related to life support or organ failure (23.0%). The most frequent
      causes of ICU admission were those associated with the least severity in the ICU.
      During the study period, the rate of pregnancy-related ICU admissions decreased
      from 3.9 to 3.4 per 1,000 deliveries (p < 0.001), whereas the overall severity of
      cases increased with longer stays, higher Simplified Acute Physiology Score II
      scores, and a greater proportion of SUP REA codes (all p < 0.001). Analysis by
      principal diagnosis showed that the severity of the condition of women admitted
      to ICU significantly increased over time for hemorrhages and hypertensive
      complications. CONCLUSIONS: The rate of women with pregnancy-related ICU
      admissions decreased and the severity of their cases increased. Most ICU
      admissions remained related to the least severe conditions. This raises the issue
      of the most appropriate organization of care for women with pregnancy-related
      conditions who require continuous surveillance but not necessarily intensive
      care.

PMID- 25377017
TI  - Nonbeneficial treatment Canada: definitions, causes, and potential solutions from
      the perspective of healthcare practitioners*.
AB  - OBJECTIVE: Many healthcare workers are concerned about the provision of
      nonbeneficial treatment in the acute care setting. We sought to explore the
      perceptions of acute care practitioners to determine whether they perceived
      nonbeneficial treatment to be a problem, to generate an acceptable definition of
      nonbeneficial treatment, to learn about their perceptions of the impact and
      causes of nonbeneficial treatment, and the ways that they feel could reduce or
      resolve nonbeneficial treatment. DESIGN: National, bilingual, cross-sectional
      survey of a convenience sample of nursing and medical staff who provide direct
      patient care in acute medical wards or ICUs in Canada. MAIN RESULTS: We received
      688 responses (response rate 61%) from 11 sites. Seventy-four percent of
      respondents were nurses. Eighty-two percent of respondents believe that our
      current means of resolving nonbeneficial treatment are inadequate. The most
      acceptable definitions of nonbeneficial treatment were "advanced curative/life
      prolonging treatments that would almost certainly result in a quality of life
      that the patient has previously stated that he/she would not want" (88%
      agreement) and "advanced curative/life-prolonging treatments that are not
      consistent with the goals of care (as indicated by the patient)" (83% agreement).
      Respondents most commonly believed that nonbeneficial treatment was caused by
      substitute decision makers who do not understand the limitations of treatment, or
      who cannot accept a poor prognosis (90% agreement for each cause), and 52%
      believed that nonbeneficial treatment was "often" or "always" continued until the
      patient died or was discharged from hospital. Respondents believed that
      nonbeneficial treatment was a common problem with a negative impact on all
      stakeholders (> 80%) and perceived that improved advance care planning and
      communication training would be the most effective (92% and 88%, respectively)
      and morally acceptable (95% and 92%, respectively) means to resolve the problem
      of nonbeneficial treatment. CONCLUSIONS: Canadian nurses and physicians perceive
      that our current means of resolving nonbeneficial treatment are inadequate, and
      that we need to adopt new techniques of resolving nonbeneficial treatment. The
      most promising strategies to reduce nonbeneficial treatment are felt to be
      improved advance care planning and communication training for healthcare
      professionals.

PMID- 25377018
TI  - The epidemiology of chronic critical illness in the United States*.
AB  - OBJECTIVES: The epidemiology of chronic critical illness is not well
      characterized. We sought to determine the prevalence, outcomes, and associated
      costs of chronic critical illness in the United States. DESIGN: Population-based
      cohort study using data from the United States Healthcare Costs and Utilization
      Project from 2004 to 2009. SETTING: Acute care hospitals in Massachusetts, North
      Carolina, Nebraska, New York, and Washington. PATIENTS: Adult and pediatric
      patients meeting a consensus-derived definition for chronic critical illness,
      which included one of six eligible clinical conditions (prolonged acute
      mechanical ventilation, tracheotomy, stroke, traumatic brain injury, sepsis, or
      severe wounds) plus at least 8 days in an ICU. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Out of 3,235,741 admissions to an ICU during the study period,
      246,151 (7.6%) met the consensus definition for chronic critical illness. The
      most common eligibility conditions were prolonged acute mechanical ventilation
      (72.0% of eligible admissions) and sepsis (63.7% of eligible admissions). Among
      patients meeting chronic critical illness criteria through sepsis, the infections
      were community acquired in 48.5% and hospital acquired in 51.5%. In-hospital
      mortality was 30.9% with little change over the study period. The overall
      population-based prevalence was 34.4 per 100,000. The prevalence varied
      substantially with age, peaking at 82.1 per 100,000 individuals 75-79 years old
      but then declining coincident with a rise in mortality before day 8 in otherwise
      eligible patients. Extrapolating to the entire United States, for 2009, we
      estimated a total of 380,001 cases; 107,880 in-hospital deaths and $26 billion in
      hospital-related costs. CONCLUSIONS: Using a consensus-based definition, the
      prevalence, hospital mortality, and costs of chronic critical illness are
      substantial. Chronic critical illness is particularly common in the elderly
      although in very old patients the prevalence declines, in part because of an
      increase in early mortality among potentially eligible patients.

PMID- 25377019
TI  - Methicillin-resistant Staphylococcus aureus prevention strategies in the ICU: a
      clinical decision analysis*.
AB  - OBJECTIVES: ICUs are a major reservoir of methicillin-resistant Staphylococcus
      aureus. Our aim was to estimate costs and effectiveness of methicillin-resistant
      Staphylococcus aureus prevention policies. DESIGN AND INTERVENTIONS: We evaluated
      three up-to-date methicillin-resistant Staphylococcus aureus prevention policies,
      namely, 1) nasal screening and contact precautions of methicillin-resistant
      Staphylococcus aureus-positive patients; 2) nasal screening, contact precautions,
      and decolonization (targeted decolonization) of methicillin-resistant
      Staphylococcus aureus carriers; and 3) universal decolonization without
      screening. We implemented a decision-analytic model with deterministic and
      probabilistic analyses. Methicillin-resistant Staphylococcus aureus infections
      averted, quality-adjusted life years gained, and incremental cost-effectiveness
      ratios were calculated. Cost-effectiveness planes and acceptability curves were
      plotted for various willingness-to-pay thresholds to address uncertainty.
      MEASUREMENTS AND MAIN RESULTS: At base-case scenario, universal decolonization
      was the dominant strategy; it averted 1.31% and 1.59% of methicillin-resistant
      Staphylococcus aureus infections over targeted decolonization and screening and
      contact precautions, respectively, and saved $16,203/quality-adjusted life year
      over targeted decolonization and 14,562/quality-adjusted life year over screening
      and contact precautions. Results were robust in sensitivity analysis for a wide
      range of input variables. In probabilistic analysis, universal decolonization
      increased quality-adjusted life years by 1.06% (95% CI, 1.02-1.09) over targeted
      decolonization and by 1.29% (95% CI, 1.24-1.33) over screening and contact
      precautions; universal decolonization resulted in average savings of $172 (95%
      CI, $168-$175) and $189 (95% CI, $185-$193) over targeted decolonization and
      screening and contact precautions, respectively. With willingness-to-pay
      threshold per quality-adjusted life year gained ranging from $0 to $50,000,
      universal decolonization was dominant over targeted decolonization in 67.5-75.4%
      and dominant over screening and contact precautions in 66.0-75.4%. CONCLUSIONS:
      In the ICU setting, universal decolonization outperforms the other two strategies
      and is likely to be cost-effective even at low willingness-to-pay thresholds.
      Assuming 700 annual ICU admissions in an average 12-bed ICU, the projected annual
      savings reach $129,500 to $135,100.

PMID- 25377020
TI  - Cytomegalovirus seroprevalence as a risk factor for poor outcome in acute
      respiratory distress syndrome*.
AB  - OBJECTIVE: Cytomegalovirus reactivation may complicate critical illness in latent
      carriers of the virus, even in patients who were previously immunocompetent.
      Patients with acute respiratory distress syndrome are considered to be prone for
      reactivation. Prophylactic antiviral therapy in immunocompetent cytomegalovirus
      seropositive patients admitted to the ICU with acute respiratory distress
      syndrome has therefore been proposed. We assessed cytomegalovirus seroprevalence
      as a risk factor for morbidity and mortality in patients with acute respiratory
      distress syndrome. DESIGN: Prospective observational cohort study. We used the
      number of days alive and free of mechanical ventilation on day 28 as a composite
      outcome measure and used multivariable ordinal logistic regression analyses to
      adjust for potential confounders. SETTING: ICUs of two tertiary care hospitals in
      The Netherlands. PATIENTS: We included all newly admitted patients with acute
      respiratory distress syndrome who received mechanical ventilation for at least 4
      days. Patients with known immunocompromise and those receiving antiviral
      treatment prior to ICU admission were excluded. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Over a 2-year period, 306 patients were included, 209 (68%) of
      whom were cytomegalovirus seropositive. Cytomegalovirus reactivation occurred in
      53 of these cases (26%). One hundred patients (33%) died or continued to be
      mechanically ventilated by day 28. After adjustment for confounding,
      cytomegalovirus seroprevalence was not associated with the primary outcome (crude
      odds ratio, 1.09; 95% CI, 0.70-1.70; adjusted odds ratio, 1.01; 95% CI, 0.64
      1.59). Seroprevalence was also not associated with poor outcome in any of the
      prespecified subgroup analyses. However, a significant association was found in a
      post hoc subgroup of patients who had developed acute respiratory distress
      syndrome in a setting of septic shock (adjusted odds ratio, 2.86; 95% CI, 1.32
      6.23). The time course of pulmonary markers in survivors was comparable between
      the two serogroups. CONCLUSIONS: Cytomegalovirus seroprevalence is not associated
      with prolonged mechanical ventilation or increased mortality in critically ill
      patients with acute respiratory distress syndrome, with possible exception of
      patients presenting with septic shock. Therefore, a prevention strategy targeting
      an unselected cohort of seropositive patients with acute respiratory distress
      syndrome is unlikely to show any meaningful benefit.

PMID- 25377021
TI  - Dysphagia--a common, transient symptom in critical illness polyneuropathy: a
      fiberoptic endoscopic evaluation of swallowing study*.
AB  - OBJECTIVES: Critical illness polyneuropathy is a common disorder in the
      neurological ICU. Dysphagia is well known to deteriorate outcome in the ICU. The
      prevalence of dysphagia in critical illness polyneuropathy is not known. The aim
      of this study was to evaluate the prevalence of dysphagia in critical illness
      polyneuropathy using fiberoptic endoscopic evaluation of swallowing. DESIGN:
      Prospective, cohort study. SETTING: Neurological rehabilitation ICU. PATIENTS:
      Twenty-two patients with critical illness polyneuropathy. INTERVENTIONS: Clinical
      swallowing examination and serial fiberoptic endoscopic evaluation of swallowing
      (days 3, 14, and 28 after admission). MEASUREMENTS AND MAIN RESULTS: Swallowing
      of saliva, pureed consistencies, and liquids was tested using fiberoptic
      endoscopic evaluation of swallowing at three different time points. The
      penetration-aspiration scale by Rosenbek et al and the secretion severity rating
      scale by Murray et al were used for grading. Functional outcome after
      rehabilitation was assessed using the functional independence measure.:
      Pathologic swallowing was found in 20 of 22 patients (91%). Hypesthesia of
      laryngeal structures was found in 17 of 22 patients (77%) during the first
      fiberoptic endoscopic evaluation of swallowing. Over the 4-week follow-up period,
      laryngeal hypesthesia resolved in 75% of affected cases. Pureed consistencies
      were swallowed safely in 18 of 22 cases (82%), whereas liquids and saliva showed
      high aspiration rates (13 of 17 [78%] and 10 of 22 [45%], respectively).
      Swallowing function recovered completely in 21 of 22 (95%) within 4 weeks.
      CONCLUSIONS: Dysphagia is frequent among patients with critical illness
      polyneuropathy treated in the ICU. Old age, chronic obstructive pulmonary
      disease, the mode of mechanical ventilation, the prevalence of tracheal tubes,
      and behavioral "learned nonuse" may all be contributing factors for the
      development of dysphagia in critical illness polyneuropathy. Complete recovery
      occurs in a high percentage of affected individuals within 4 weeks.

PMID- 25377022
TI  - Hot flushes and night sweats are associated with coronary heart disease risk in
      midlife: a longitudinal study.
AB  - OBJECTIVE: The purpose of this study was to investigate associations between
      vasomotor menopausal symptoms (VMS), i.e. hot flushes and night sweats, and the
      incidence of coronary heart disease (CHD). DESIGN: A prospective cohort study.
      SETTING AND POPULATION: 11 725 women, aged 45-50 years at baseline in 1996, were
      followed up at 3-year intervals for 14 years. METHODS: Self-reported VMS and
      incident CHD were measured at each survey. MAIN OUTCOME MEASURE: We determined
      the association between VMS and CHD at the subsequent survey, using generalised
      estimating equation analysis, adjusting for time-varying covariates. RESULTS: At
      baseline, 14% reported rarely, 17% reported sometimes, and 7% reported often
      having night sweats. During follow-up, 187 CHD events occurred. In the age
      adjusted analysis, women who reported their frequency of experiencing hot flushes
      and night sweats as 'often' had a greater than two-fold increased odds of CHD (OR
      hot flushes 2.18, 95% CI 1.49-3.18; OR night sweats 2.38, 95% CI 1.62-3.50)
      compared with women with no symptoms (P trend < 0.001 for frequency of symptoms).
      Adjustment for menopausal status, lifestyle factors, body mass index, diabetes,
      and hypertension attenuated the associations (OR hot flushes 1.70, 95% CI 1.16
      2.51, P trend = 0.01; OR night sweats 1.84, 95% CI 1.24-2.73), P trend = 0.004).
      CONCLUSIONS: Women who report having hot flushes or night sweats 'often' have an
      increased risk of developing CHD over a period of 14 years, even after taking the
      effects of age, menopause status, lifestyle, and other chronic disease risk
      factors into account.

PMID- 25377023
TI  - Is suppressed thyroid-stimulating hormone (TSH) associated with subclinical
      depression in the Danish General Suburban Population Study?
AB  - BACKGROUND: The first phase of the Danish General Suburban Population Study
      (GESUS) including 8214 individuals was an attempt to evaluate the association
      between subclinical hypothyroidism without or with elevated peroxidase antibodies
      and depression. No such association was found. In the second phase, including
      14,787 individuals, we have focused on suppressed TSH (thyroid-stimulating
      hormone) and depression. AIMS: To evaluate to what extent suppressed TSH is
      associated with subclinical depression. METHODS: The total scores of the Major
      Depression Inventory (MDI) were used to evaluate subclinical depression, both by
      its total score and by an algorithm of the subthreshold depressed by presence of
      at least three of the 10 ICD-10 depression symptoms. Serum levels of TSH were
      used to classify the individuals into suppressed (TSH < 0.4 mIU/l), elevated (TSH
      >= 3.8 mIU/l) and normal reference (TSH between 0.4 and 3.7 mIU/l). RESULTS: We
      identified 285 individuals with suppressed TSH and 1266 individuals with elevated
      TSH. The MDI total score was 7.55 in suppressed TSH individuals, 6.22 in elevated
      TSH individuals and 6.52 in normal reference individuals (P = 0.01). When the MDI
      was used diagnostically to identify subclinical depression, the prevalence was
      8.07% in suppressed TSH individuals, 5.8% in normal reference individuals and
      5.29% in elevated TSH individuals. CONCLUSION: This population-based study
      supports that persons with suppressed TSH (subclinical hyperthyroidism) seem to
      have a risk, although small, of subclinical depression.

PMID- 25377024
TI  - Evaluating the INSPIRE measure of staff support for personal recovery in a
      Swedish psychiatric context.
AB  - BACKGROUND: Recovery is understood to be an individual process that cannot be
      controlled, but can be supported and facilitated at the individual,
      organizational and system levels. Standardized measures of recovery may play a
      critical role in contributing to the development of a recovery-oriented system.
      The INSPIRE measure is a 28-item service user-rated measure of recovery support.
      INSPIRE assesses both the individual preferences of the user in the recovery
      process and their experience of support from staff. AIM: The aim of this study
      was to evaluate the psychometric properties of the Swedish version of the INSPIRE
      measure, for potential use in Swedish mental health services and in order to
      promote recovery in mental illness. METHOD: The sample consisted of 85
      participants from six community mental health services targeting people with a
      diagnosis of psychosis in a municipality in Sweden. For the test-retest
      evaluation, 78 participants completed the questionnaire 2 weeks later. RESULTS:
      The results in the present study indicate that the Swedish version of the INSPIRE
      measure had good face and content validity, satisfactory internal consistency and
      some level of instability in test-retest reliability. CONCLUSIONS: While further
      studies that test the instrument in a larger and more diverse clinical context
      are needed, INSPIRE can be considered a relevant and feasible instrument to
      utilize in supporting the development of a recovery-oriented system in Sweden.

PMID- 25377025
TI  - Consumer satisfaction with the Child and Adolescent Mental Health Service and its
      association with treatment outcome: a 3-4-year follow-up study.
AB  - BACKGROUND: Consumer satisfaction studies with the Child and Adolescent Mental
      Health Service (CAMHS) have mainly assessed evaluations in a short-term follow-up
      perspective. Adolescent reports with CAMHS have not been included nationally.
      AIMS: The purposes of this study were to explore adolescent and parental
      satisfaction with the CAMHS in a 3-4-year follow-up perspective, and to examine
      the relationships between reported consumer satisfaction and clinical parameters
      such as reason for adolescent referral, emotional/behavioral symptoms and
      treatment outcome. METHODS: Of 190 adolescent-parent pairs in a sample of CAMHS
      outpatients, 120 completed a Consumer Satisfaction Questionnaire. Parents
      assessed adolescent emotional/behavior problems both at baseline and at follow-up
      by completing the Child Behavior Checklist (CBCL). Correlations were examined
      between adolescent and parental evaluations. The relationships between service
      satisfaction and symptom load at baseline and follow-up and treatment outcome at
      follow-up were explored. RESULTS: Overall, adolescents and parents were satisfied
      with the services received from the CAMHS. The correlations between adolescent
      and parent consumer satisfaction ratings were low to moderate. Consumer
      satisfaction was significantly and negatively correlated with symptom load on the
      CBCL Total Problems scores at baseline, but not at follow-up. There was no
      difference in satisfaction levels between those who improved after treatment and
      those who did not. CONCLUSIONS: Given the differences in informant ratings of
      consumer satisfaction, it is important to include both adolescent and parental
      perceptions in evaluations of CAMHS services and treatment outcomes. Consumer
      satisfaction should serve as a supplement to established standardized outcome
      measures.

PMID- 25377026
TI  - Clinical issues in renal transplantation in the elderly.
AB  - Kidney transplantation is the best renal replacement therapy option and is
      superior to dialysis in elderly end-stage renal disease (ESRD) patients.
      Furthermore, the outcome of transplantation in the elderly is comparable to
      younger patients in terms of allograft survival. The exact nature of this
      phenomenon is not completely clear. As the elderly population continues to grow,
      it becomes more important to identify specific issues associated with kidney
      transplantation. In particular, elderly transplant recipients might have a lower
      chance of acute rejection as their immune systems seem to be less reactive. This
      might predispose elderly recipients to greater risk of post-transplant infectious
      complications or malignancies. Furthermore, due to differences in
      pharmacokinetics, elderly recipients might require lower doses of
      immunosuppressive medication. As the main cause of graft failure in the elderly
      is death with a functioning graft and also considering the scarcity of donor
      organs, it might make sense to recommend transplanting elderly recipients with
      extended criteria donor kidneys. This approach would balance shorter patient
      survival compared to younger recipients. In conclusion, old age should not
      preclude ESRD patients from kidney transplantation. However, specific differences
      that have to do with immunosuppression and other aspects of managing elderly
      transplant recipients should be considered. 

PMID- 25377027
TI  - Oscillatory haematopoiesis in adults with sickle cell disease treated with
      hydroxycarbamide.
AB  - Hydroxycarbamide therapy has been associated with significant oscillations in
      peripheral blood counts from myeloid, lymphoid and erythroid lineages in patients
      with polycythaemia vera and chronic myeloid leukaemia. We retrospectively
      evaluated serial blood counts over an 8-year period from 44 adult patients with
      sickle cell disease receiving hydroxycarbamide. Platelet counts, leucocyte
      counts, haemoglobin values and reticulocyte counts, apportioned by
      hydroxycarbamide status, were analysed using a Lomb-Scargle periodogram
      algorithm. Significant periodicities were present in one or more counts in 38
      patients receiving hydroxycarbamide for a mean duration of 4.81 years. Platelet
      and leucocyte counts oscillated in 56.8% and 52.3% of patients, respectively.
      These oscillations generally became detectable within days of initiating therapy.
      During hydroxycarbamide therapy, the predominant periods of oscillation were 27
      +/- 1 d for platelet counts and 15 +/- 1 d for leucocyte counts. Despite an
      absolute decrease in leucocyte and platelet counts during hydroxycarbamide
      treatment, the amplitudes between nadirs and zeniths remained similar regardless
      of exposure. Our observations appear consistent with previously proposed models
      of cyclic haematopoiesis, and document that hydroxycarbamide-induced oscillations
      in blood counts are innocuous phenomena not limited to myeloproliferative
      disorders as described previously. We speculate the known cell cycle inhibitory
      properties of hydroxycarbamide may accentuate otherwise latent constitutive
      oscillatory haematopoiesis.

PMID- 25377028
TI  - Associations with low rates of postpartum glucose screening after gestational
      diabetes among Indigenous and non-Indigenous Australian women.
AB  - OBJECTIVES: To explore factors associated with postpartum glucose screening among
      women with Gestational Diabetes Mellitus (GDM). METHODS: A retrospective study
      using linked records from women with GDM who gave birth at Cairns Hospital in Far
      North Queensland, Australia, from 1 January 2004 to 31 December 2010. RESULTS:
      The rates of postpartum Oral Glucose Tolerance Test (OGTT) screening, while
      having increased significantly among both Indigenous* and non-Indigenous women
      from 2004 to 2010 (HR 1.15 per year, 95%CI 1.08-1.22, p<0.0001), remain low,
      particularly among Indigenous women (10% versus 27%, respectively at six months
      postpartum). Indigenous women in Cairns had a longer time to postpartum OGTT than
      Indigenous women in remote areas (HR 0.58, 0.38-0.71, p=0.01). Non-Indigenous
      women had a longer time to postpartum OGTT if they: were born in Australia (HR
      0.76, 0.59-1.00, 0.05); were aged <25 years (HR 0.45, 0.23-0.89, p=0.02); had
      parity >5 (HR 0.33, 0.12-0.90, p=0.03); smoked (HR 0.48, 0.31-0.76, p=0.001); and
      did not breastfeed (HR 0.09, 0.01-0.64, p=0.02). CONCLUSIONS: Postpartum diabetes
      screening rates following GDM in Far North Queensland are low, particularly among
      Indigenous women, with lower rates seen in the regional centre; and among non
      Indigenous women with indicators of low socioeconomic status. IMPLICATIONS:
      Strategies are urgently needed to improve postpartum diabetes screening after GDM
      that reach women most at risk.

PMID- 25377029
TI  - "Informing" and "consenting": ethical concerns regarding illiterate and
      vulnerable participants in clinical trials.

PMID- 25377030
TI  - Assessing capabilities in India today and the role of "outside" opinions.

PMID- 25377031
TI  - Ebola virus disease outbreak: incorporating ethical analysis into the health
      system response.

PMID- 25377032
TI  - Integrity in medical practice.
AB  - Among the many moral terms that are in common use in public discourse,
      "integrity" not only occurs more frequently but also seems to have less ambiguity
      than generic terms such as"good", "bad" and"ethical". The notion of integrity
      captures a particular state of being and the word is used to characterise people
      as well as events. Some examples are "She behaved with integrity", or "She is a
      person with integrity", as well as "It was an act of integrity". In this sense,
      the word is a powerful expression of a particular sense of being ethical. 

PMID- 25377033
TI  - Commentary--Controversies surrounding mercury in vaccines: autism denial as
      impediment to universal immunisation.
AB  - In 2004, the US Center for Disease Control (CDC) published a paper showing that
      there is no link between the age at which a child is vaccinated with MMR and the
      vaccinated children's risk of a subsequent diagnosis of autism. One of the
      authors, William Thompson, has now revealed that statistically significant
      information was deliberately omitted from the paper. Thompson first told Dr S
      Hooker, a researcher on autism, about the manipulation of the data. Hooker
      analysed the raw data from the CDC study afresh. He confirmed that the risk of
      autism among African American children vaccinated before the age of 2 years was
      340% that of those vaccinated later. 

PMID- 25377034
TI  - Ethical issues in the care of persons living with haemophilia in India.
AB  - The recent series of ad interim orders issued by the Bombay High Court under
      ordinary original civil jurisdiction following public interest litigation (PIL)
      on the provision of free clotting factor concentrates for persons living with
      haemophilia, especially those below the poverty line and emergency cases,
      highlights the need to think about the ethicality of various aspects of access to
      medicine and the rights of patients suffering from rare diseases from the public
      health perspective. The PIL (number 82/2012) [Vinay Vijay Nair and Ors vs.
      Department of Health, State of Maharashtra and Ors), which calls for free
      treatment for all haemophiliacs who go to the designated hospitals, was followed
      by the issuance of five ad interim orders (July 19, 2012, October 22, 2012,
      November 6, 2012, January 24, 2013, and March 19, 2013).

PMID- 25377035
TI  - Ethical issues in recruitment of "healthy volunteers": study of a clinical
      research organisation in Hyderabad.
AB  - This paper raises some of the ethical issues involved in the recruitment of
      healthy volunteers (HVs) by clinical research organizations (CROs) for
      bioavailability and bioequivalent (BA/BE) studies. It also explores the
      underlying reasons for the participation of the HVs and their interaction with
      the CROs. The findings are based on the data collected from 50 HVs participating
      in a BA/BE study conducted by a CRO in Hyderabad and from the key officials
      involved in it. The findings indicate the existence of various complex networks,
      throw some light on the role of middlemen ("Anna") and the negotiation process,
      and give us an insight into the social norms and values that compelled the HVs to
      participate in the study. The paper offers a critical analysis of a few ethical
      concerns. 

PMID- 25377036
TI  - Health equity for internal migrant labourers in India: an ethical perspective.
AB  - In the developing countries, internal migration is a survival strategy for many
      labourers in search of a better livelihood and opportunities. It is inevitable
      that many of them will leave their home towns and villages in the coming years,
      and that the future will see an increase in the number of migrant labourers in
      developing countries such as India. Migrant workers face unique health problems
      and it is important for the health system to prepare itself to face these. In
      this context, the system will need to address certain key ethical issues. There
      is plenty of published literature on international migration and its ethical
      aspects.However, there is a scarcity of information on ethical issues relating to
      internal migration. This article examines these issues in the context of India.
      It addresses the issues of equity, non-discrimination,the provision of culturally
      competent care to migrants, allocation of scarce resources, and achieving a
      balance between benefits and risks for migrants. Our analysis should be
      considered while planning any healthcare intervention for internal migrant
      workers in all developing countries.

PMID- 25377037
TI  - A study of promotional advertisements of drugs in a medical journal: an ethics
      perspective.
AB  - The study assessed 54 advertisements of 145 different drugs, published over one
      year (from December 2011 to November 2012) in an Indian medical journal,
      circulated widely mainly among general practitioners (GPs). The ethical
      guidelines of the World Health Organization (WHO) and Organisation of
      Pharmaceutical Producers of India (OPPI) for medicinal drug promotion were
      applied. The brand name was mentioned in all advertisements (100% compliance both
      with the WHO and OPPI criteria) and the names of the active ingredients were also
      mentioned in 128 (90.14%) advertisements. However, major adverse drug reactions
      were mentioned in only two advertisements (1.37%); precautions, contraindications
      and warnings in only two (1.37%); and major interactions in only one (0.68%).
      Only three advertisements (2.06%) were well substantiated with references. To
      ensure the ethical promotionof drugs among GPs, journals must introduce
      compulsory review and appraisal of promotional advertisements by a dedicated
      review board, including at least one member trained in pharmacology and one
      representative from the medical division of a pharmaceutical company. 

PMID- 25377038
TI  - Diagnosis of autism, abortion and the ethics of childcare in Yoruba culture.
AB  - This paper examines the ethics of childcare in Yoruba culture in the contexts of
      autism and abortion. The traditional Yoruba moral principles of ibikojuibi
      (equality of humans at birth) and ajowapo (solidarity) have been theoretically
      developed to establish the personhood of autistic children and provide a
      justification for not aborting foetuses with autism. Despite these
      justifications, this paper argues that there is a need for contextual rethinking,
      which would allow for: (i) prenatal genetic testing, as well as abortion of
      foetuses with a high risk of the autism mutation, and (ii) early clinical
      diagnosis and treatment of autistic children in contemporary Yoruba society.

PMID- 25377039
TI  - Doctors do cry.
AB  - Physicians have tried to understand whether crying for a patient is a raw emotion
      that demonstrates their lack of control over themselves and the situation, or
      whether it is a sign of humanity and concern for one's fellow beings. Studies on
      medical students and doctors'narrations of times when they have shed tears over a
      patient's suffering or death have established beyond doubt that medical students
      and physicians are not immune to their patients'suffering and may cry when
      overwhelmed by stress and emotions. Even though humanity is the cornerstone of
      medicine, depersonalisation has somehow crept into the physician-patient
      relationship and crying is considered incompatible with the image of a good
      physician, who is supposed to be strong, confident and fully in charge. Thus,
      crying has been equated to weakness and at times, incompetence. This could be
      attributed to the fact that our medical curriculum has ingrained in us the belief
      that emotion clouds rationality and prevents us from being objective while making
      decisions regarding a patient's clinical progress. Our curriculum fails to teach
      us how to handle emotional situations, witness the dying process, communicate bad
      news, interact with the bereaved during the period of grief immediately following
      death, and reduce the professional stress involved in working with newly bereaved
      persons. Our training focuses on cure, amelioration of disease and the
      restoration of good health, with little emphasis on death, which is an absolute
      reality. It is crucial that medical educators take note of these lacunae in the
      curriculum. Physicians and teachers must recognise and accept the emotions that
      medical students experience in these situations, and teach them to offer their
      patients a sound blend of rationality and compassion with an attitude of
      humility. 

PMID- 25377040
TI  - Last call for informed consent: confused proxies in extra-emergency conditions.
AB  - Informed consent has become a part of medical practice in Albania only recently,
      during a time when there has been a substantial increase in claims of
      malpractice. Its original aim was to provide patients with information to help
      them make decisions on particular health interventions. We describe the case of a
      patient who developed an unexpected surgical complication and desperately needed
      a second intervention, and the futility of obtaining informed consent in the
      setting of a medical emergency. The circumstances of the emergency might turn out
      to be too complicated and confusing for the proxies. The, role of proxies is not
      defined in the Albanian laws and bylaws. Seeking and eventually obtaining the
      necessary signatures and permissions in an emergency cannot be justified because
      the lack of time in such circumstances might be a major obstacle to sound and
      comprehensive communication, and lack of communication could give rise to
      mistrust, with all its potential consequences. 

PMID- 25377041
TI  - Commentary--Informed consent for a life-saving operation in Albania and in India.

PMID- 25377042
TI  - Mental fitness certificates: are psychiatrists in the dock?

PMID- 25377043
TI  - Putting patients first? Reflections concerning the "Consensus Framework for
      Ethical Collaboration".

PMID- 25377044
TI  - Sex education is the need of the hour.

PMID- 25377045
TI  - From physician to anxious parent.

PMID- 25377046
TI  - Molecular analyses in the diagnosis of myeloproliferative neoplasm-related
      splanchnic vein thrombosis.

PMID- 25377047
TI  - Symptomatic striopallidodentate calcinosis (Fahr's syndrome) in a thalassemic
      patient with hypoparathyroidism.

PMID- 25377048
TI  - The role of mast cells in atherosclerosis.
AB  - Rupture of an atherosclerotic plaque is the major underlying cause of adverse
      cardiovascular events such as myocardial infarction or stroke. Therapeutic
      interventions should therefore be directed towards inhibiting growth of
      atherosclerotic lesions as well as towards prevention of lesion destabilization.
      Interestingly, the presence of mast cells has been demonstrated in both murine
      and human plaques, and multiple interventional murine studies have pointed out a
      direct role for mast cells in early and late stages of atherosclerosis. Moreover,
      it has recently been described that activated lesional mast cells correlate with
      major cardiovascular events in patients suffering from cardiovascular disease.
      This review focuses on the effect of different mast cell derived mediators in
      atherogenesis and in late stage plaque destabilization. Also, possible ligands
      for mast cell activation in the context of atherosclerosis are discussed.
      Finally, we will elaborate on the predictive value of mast cells, together with
      therapeutic implications, in cardiovascular disease.

PMID- 25377050
TI  - Incidence and mortality prognosis of dysnatremias in neurologic critically ill
      patients.
AB  - BACKGROUND: Dysnatremia, which is associated with increased mortality in general
      intensive care units (ICU), has not been thoroughly studied in neurologic ICU
      (NICU). METHODS: Prevalence of dysnatremia was retrospectively assessed. The
      multivariable binary logistic regression model was used to determine the
      influence of dysnatremia on mortality. RESULTS: Of 519 patients, 106 (20.4%) were
      admitted with hyponatremia and 177 (34.10%) with hypernatremia. Hypernatremia was
      detected in 69 (13.29%) patients on admission to NICU and in 108 patients
      (20.81%) during the ICU stay. However, the incidence of dysnatremia did not
      differ across the neurological categories (p = 0.4690). ICU stay in patients with
      acquired hypernatremia (22.3 +/- 25.35 days) was longer than those with admission
      hypernatremia (13.5 +/- 12.8 days) or with consistent normonatremia (16.16 +/-
      20.06 days). The other indicators such as Acute Physiology and Chronic Health
      Evaluation II, Glasgow Coma Scale score, urinary catheterization, and incidence
      of pneumonia were also associated with the serum sodium concentrations.
      Hypernatremia both on admission and acquired in NICU could significantly
      differentiate between survivors and nonsurvivors (p = 0.002 and <0.0001).
      However, only NICU-acquired hypernatremia was the independent risk factor for
      mortality with high sensitivity (p = 0.000). CONCLUSIONS: Dysnatremia is more
      common in NICU, whereas only acquired-hypernatremia was independently associated
      with outcome.

PMID- 25377051
TI  - Sleep and school attendance in adolescence: results from a large population-based
      study.
AB  - BACKGROUND: The aim of this study was to examine the link between adolescent
      sleep and non-attendance in school. METHODS: A large population-based study from
      Norway conducted in 2012, the youth@hordaland study, surveyed 8,347 adolescents
      aged 16-19 years (54% girls). Self-reported sleep measures included bedtime, rise
      time, sleep duration, sleep efficiency, sleep onset latency (SOL), wake after
      sleep onset (WASO), insomnia symptoms, tiredness, and sleepiness. School
      attendance was obtained from national administrative registries. RESULTS: Most
      sleep parameters were associated with increased risk of school non-attendance.
      After adjusting for gender and socioeconomic status, short sleep duration and
      sleep deficiency were the sleep measures with the highest odds of non-attendance
      (OR=4.61, CI 95% 3.29-6.46) and (OR=3.26, CI 95% 2.67-3.99), respectively). Also,
      large bedtime discrepancies in weekend versus weekdays were associated with non
      attendance (OR=2.43, CI 95% 1.93-2.02), as well as insomnia (OR=2.25, CI % 1.89
      2.67) and daytime tiredness (OR=2.09, CI 95% 1.70-2.57). The associations were
      somewhat reduced after additional adjustment for depression, but remained
      significant in the fully adjusted model. CONCLUSION: The demonstrated
      relationship between sleep problems and school absence suggests that careful
      assessment of sleep is warranted when adolescents present with extensive school
      absence future studies on how the sleep-school absence relationship in
      adolescence may impact later work affiliation in adulthood are needed.

PMID- 25377052
TI  - Socioeconomic differences in emotional symptoms among adolescents in the Nordic
      countries: recommendations on how to present inequality.
AB  - AIMS: This comparative study examines absolute and relative socioeconomic
      differences in emotional symptoms among adolescents using standardised data from
      five Nordic countries and gives recommendations on how to present socioeconomic
      inequality. METHODS: The Health Behaviour in School-aged Children (HBSC)
      international cross-sectional study from 2005/2006 provided data on 29,642 11-15
      year-old adolescents from nationally random samples in Denmark, Finland, Iceland,
      Norway and Sweden. The outcome was daily emotional symptoms. Family Affluence
      Scale (FAS) was used as indicator of socioeconomic position. We applied four
      summary measures of inequality: Prevalence Difference, Odds Ratio, Slope Index of
      Inequality and Relative Index of Inequality, and presented the socioeconomic
      inequality by a graphical illustration of the prevalence of emotional symptoms,
      the size of the FAS groups and the summary indices of inequality in each country.
      RESULTS: The prevalence of emotional symptoms ranged from 8.1% in Denmark to
      13.2% in Iceland. There were large country variations in the size of the low FAS
      group ranging from 2% in Iceland to 12% in Finland. The largest absolute and
      relative socioeconomic inequalities were found in Iceland and the smallest in
      Finland for girls and in Denmark for boys. CONCLUSIONS: Emotional symptoms were
      more common among nordic adolescents from low affluence families this association
      appeared in the study of both absolute and relative inequality. A comprehensive
      presentation of socioeconomic inequality should include the prevalence of the
      health outcome, the size of the socioeconomic groups, and the regression line
      representing the summary indices of inequality.

PMID- 25377053
TI  - The need for interdisciplinary dialog in evolution education: a comment on the
      responses by Ware & Gelman and Shtulman.

PMID- 25377054
TI  - Editorial.

PMID- 25377055
TI  - Clinical and biological determinants of sclerostin plasma concentration in
      hemodialysis patients.
AB  - BACKGROUND: Sclerostin is a potent inhibitor of bone formation, but the meaning
      of its serum levels remains undetermined. We evaluated the association between
      sclerostin levels and clinical or biological data in hemodialyzed patients (HD),
      notably parathormone (PTH), biomarkers of bone turnover, vascular calcifications
      and mortality after 2 years. METHODS: 164 HD patients were included in this
      observational study. The calcification score was assessed with the Kauppila
      method. Patients were followed for 2 years. RESULTS: Median sclerostin levels
      were significantly (p < 0.0001) higher in HD versus healthy subjects (n = 94)
      (1,375 vs. 565 pg/ml, respectively). In univariate analysis a significant
      association (p < 0.05) was found between sclerostin and age, height, dialysis
      vintage, albumin, troponin, homocysteine, PTH, C-terminal telopeptide of collagen
      type I, bone-specific alkaline phosphatase and osteoprotegerin, but not with the
      calcification score. In a multivariate model, the association remained with age,
      height, dialysis vintage, troponin, homocysteine, phosphate, PTH, but also with
      vascular calcifications. Association was positive for all variables, except PTH
      and vascular calcifications. The baseline sclerostin concentration was not
      different in survivors and non-survivors. CONCLUSIONS: We confirm a higher
      concentration of sclerostin in HD patients, a positive association with age and a
      negative association with PTH. A positive association with phosphate,
      homocysteine and troponin calls for additional research. The clinical interest of
      sclerostin to assess vascular calcifications in HD is limited and no association
      was found between sclerostin and mortality.

PMID- 25377056
TI  - Analytic characteristics of three Bayer contour blood glucose monitoring systems
      in neonates.
AB  - Hypoglycemia in infants is common, is difficult to recognize, and may lead to
      permanent neurologic impairment. Low glucose concentrations and high hematocrits
      in newborns pose significant analytic challenges for whole blood glucose meters.
      Three Bayer glucose monitoring systems were evaluated using 211 blood samples
      from 162 neonates (age range 5 hours to 29 days, median age 3 days). Hematocrit
      and whole blood glucose were determined in heparinized whole blood, and plasma
      glucose was determined using the Roche Cobas 6000. Accuracy was evaluated against
      plasma concentrations using ISO 15197:2013 and CLSI POCT 12-A3 criteria. Glucose
      imprecision on the Cobas system was 1.8-2.6% (CV) from 26-610 mg/dL. Imprecision
      across all meter systems was 2.8% (CV) at 130 mg/dL. Glucose concentrations,
      hematocrit, and total bilirubin ranged from 20-150 mg/dL, 18 -75%, and 0.5-19.6
      mg/dL, respectively. Linear regression analysis of whole blood versus plasma for
      the 3 combined systems yielded an average slope of 1.06 and correlation
      coefficient greater than 0.980. Bias between the Contour and Cobas was not
      significantly correlated with hematocrit. Greater than 99% of meter results were
      within 15 mg/dL and 20% of plasma results at glucose concentrations <= 75 and >
      75 mg/dL, respectively. Of meter results, 97% were within 12.5 mg/dL of plasma
      results at concentrations <= 100 mg/dL, while 96% of meter results were within
      12.5% of plasma at concentrations > 100 mg/dL. The Bayer CONTOUR Blood Glucose
      Monitoring Systems exceed ISO 15197:2013 and CLSI criteria in neonatal blood
      samples.

PMID- 25377057
TI  - Meeting report: the 1st BRG-training school in Asia, a first step in the building
      of an ASEAN encapsulation network.

PMID- 25377058
TI  - Transoral resection of laryngeal and hypopharyngeal cancer is an established
      surgical procedure.

PMID- 25377059
TI  - Erratum to: Sophono Alpha System and subtotal petrosectomy with external auditory
      canal blind sac closure.

PMID- 25377060
TI  - Assessment of the correlation between nasal septal deviation and compensatory
      hypertrophy of the middle turbinate.
AB  - The aim of the study was to investigate the relationship between nasal septal
      deviation and the middle turbinate hypertrophy using computed tomography. In this
      retrospective analysis, we examined 77 patients with nasal septal deviation. The
      mucosal and bone structures of the middle turbinate and the angle of the septum
      were measured using radiological analysis. Measurements of the middle turbinate
      on the convex side were compared to those on the concave side. Measurements of
      the bony and mucosal structure area of the middle turbinate were significantly
      greater than those on the concave side. The dimensions of medial mucosa thickness
      and bone thickness were not significantly different between the convex and
      concave sides. No significant correlation was found between the angle of
      deviation and other parameters. The present findings suggest that compensatory
      middle turbinate hypertrophy was caused both by conchal bone growth and mucosal
      hypertrophy in patients with nasal septal deviation. 

PMID- 25377061
TI  - A systematic review of barriers to data sharing in public health.
AB  - BACKGROUND: In the current information age, the use of data has become essential
      for decision making in public health at the local, national, and global level.
      Despite a global commitment to the use and sharing of public health data, this
      can be challenging in reality. No systematic framework or global operational
      guidelines have been created for data sharing in public health. Barriers at
      different levels have limited data sharing but have only been anecdotally
      discussed or in the context of specific case studies. Incomplete systematic
      evidence on the scope and variety of these barriers has limited opportunities to
      maximize the value and use of public health data for science and policy. METHODS:
      We conducted a systematic literature review of potential barriers to public
      health data sharing. Documents that described barriers to sharing of routinely
      collected public health data were eligible for inclusion and reviewed
      independently by a team of experts. We grouped identified barriers in a taxonomy
      for a focused international dialogue on solutions. RESULTS: Twenty potential
      barriers were identified and classified in six categories: technical,
      motivational, economic, political, legal and ethical. The first three categories
      are deeply rooted in well-known challenges of health information systems for
      which structural solutions have yet to be found; the last three have solutions
      that lie in an international dialogue aimed at generating consensus on policies
      and instruments for data sharing. CONCLUSIONS: The simultaneous effect of
      multiple interacting barriers ranging from technical to intangible issues has
      greatly complicated advances in public health data sharing. A systematic
      framework of barriers to data sharing in public health will be essential to
      accelerate the use of valuable information for the global good.

PMID- 25377062
TI  - Interfacial processes studied by coupling electrochemistry at the polarised
      liquid-liquid interface with in situ confocal Raman spectroscopy.
AB  - Interfacial processes controlled by ion transfer voltammetry at the interface
      between two immiscible electrolyte solutions were studied by in situ Raman
      spectroscopy. Raman spectra of the interface between a 5 mM NaCl aqueous solution
      and 10 mM bis(triphenyl-phosphoranydieneammonium) tetrakis(4-chlorophenyl)borate
      in 1,2-dichloroethane were recorded at open circuit potential and at various
      interfacial potential differences. At open-circuit potential, Raman peaks
      assigned to vibrational modes of 1,2-dichloroethane are clearly visible and peaks
      of weak intensity are measured for the organic electrolyte ions. When a negative
      interfacial potential difference is applied, the intensity of the peaks of the
      cation of the organic electrolyte increases, confirming its transfer induced by
      the interfacial potential difference applied. The electrochemically assisted
      generation of mesoporous silica deposits was then followed by in situ confocal
      Raman spectroscopy. The condensation of mesoporous silica was controlled by the
      transfer of cetyltrimethylammonium (CTA(+)) ions to an aqueous phase containing
      hydrolysed silanes. The transfer of CTA(+) at the interface was monitored in situ
      by confocal Raman spectroscopy, and formation of silica was observed. 

PMID- 25377064
TI  - Novel mutations and mutation combinations of ryanodine receptor in a
      chlorantraniliprole resistant population of Plutella xylostella (L.).
AB  - A previous study documented a glycine to glutamic acid mutation (G4946E) in
      ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance
      in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this
      study, a field population collected in Yunnan province, China, exhibited a 2128
      fold resistance to chlorantraniliprole. Sequence comparison between resistant and
      susceptible P. xylostella revealed three novel mutations including a glutamic
      acid to valine substitution (E1338D), a glutamine to leucine substitution
      (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly
      conserved regions of RyR. Frequency analysis of all four mutations in this field
      population showed that the three new mutations showed a high frequency of 100%,
      while the G4946E had a frequency of 20%. Furthermore, the florescent ligand
      binding assay revealed that the RyR containing multiple mutations displayed a
      significantly lower affinity to the chlorantraniliprole. The combined results
      suggested that the co-existence of different combinations of the four mutations
      was involved in the chlorantraniliprole resistance. An allele-specific PCR based
      method was developed for the diagnosis of the four mutations in the field
      populations of P. xylostella. 

PMID- 25377065
TI  - Mutation analysis of Leber congenital amaurosis-associated genes in patients with
      retinitis pigmentosa.
AB  - The genetic defects underlying approximately half of all retinitis pigmentosa
      (RP) cases are unknown. A number of genes responsible for Leber congenital
      amaurosis (LCA) may also cause RP when they are mutated. Our previous study
      revealed that variants in the most frequently mutated nine exons accounted for
      approximately half of the mutations detected in a cohort of patients with LCA.
      The aim of the present study was to detect mutations in LCA-associated genes in
      patients with RP using two different strategies. Sanger sequencing was used to
      screen mutations in the nine exons in 293 patients with RP and exome sequencing
      was used to detect variants in 12 LCA-associated genes in 157 of the 293 patients
      with RP and then to validate the variants by Sanger sequencing. Potential
      pathogenic mutations were identified in four patients with early onset RP,
      including homozygous CRB1 mutations in two patients, compound heterozygous CRB1
      mutations in one patient and compound heterozygous CEP290 mutations in one
      patient. The present study indicated that mutations in CEP290 may also be
      associated with RP but not with LCA. With the exception of CEP290, the remaining
      11 genes known to be associated with LCA but not with RP are unlikely to be a
      common cause of RP.

PMID- 25377066
TI  - Pinocembrin attenuates 6-OHDA-induced neuronal cell death through Nrf2/ARE
      pathway in SH-SY5Y cells.
AB  - Pinocembrin (PB), the most abundant flavonoid in propolis, has been known to
      display antioxidant activity. However, the mechanism as how PB can induce
      antioxidant activity remains elusive. The purpose of the present study was to
      investigate the potential neuroprotective role of PB and to delineate its
      mechanism of action against the Parkinson's disease-related neurotoxin 6
      hydroxydopamine(6-OHDA)-induced cell death in neuroblastoma SH-SY5Y cells.
      Results indicate that pretreatment with PB for 4 h significantly reduced the 6
      OHDA-induced cell viability loss, apoptotic rate and decreased Bcl-2/Bax ratio.
      In addition, PB inhibited 6-OHDA-induced oxidative stress as measured by the
      formation of reactive oxygen species, the level of malondialdehyde, mitochondrial
      membrane potential, and superoxide dismutase. Moreover, we have revealed the PB
      treatment resulted in an increase in nuclear factor E2-related factor 2 (Nrf2)
      protein levels and subsequent activation of antioxidant response element (ARE)
      pathway genes of heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthetase
      (gamma-GCS) in SH-SY5Y cells. Treatment of SH-SY5Y cells with Nrf2 small
      interference RNA abolished PB-induced HO-1 and gamma-GCS expression and its
      protective effects. Taken together, these findings suggest that PB can protect
      the SH-SY5Y cells from 6-OHDA-induced oxidative cell death via Nrf2/ARE pathway.
      Thus, our study indicates that PB has a partial cytoprotective role in
      dopaminergic cell culture systems. 

PMID- 25377067
TI  - Treatment of electroencephalographic status epilepticus after cardiopulmonary
      resuscitation (TELSTAR): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Electroencephalographic (EEG) status epilepticus is described in 10
      to 35% of patients with postanoxic encephalopathy after successful
      cardiopulmonary resuscitation and is associated with case fatality rates of 90 to
      100%. It is unclear whether these EEG patterns represent a condition to be
      treated with anticonvulsants to improve outcome, or an expression of severe
      ischemic damage, in which treatment is futile. METHODS/DESIGN: TELSTAR is a
      multicenter clinical trial with two parallel groups, randomized treatment
      allocation, open label treatment, and blinded endpoint evaluation (PROBE design).
      We aim to enroll 172 adult patients with postanoxic encephalopathy and
      electroencephalographic status epilepticus after successful cardiopulmonary
      resuscitation, admitted to the ICU, in whom continuous EEG monitoring is started
      within 24 hours after admission. Patients are randomly assigned to either medical
      treatment to suppress all electrographic seizure activity, or no treatment of
      electroencephalographic status epilepticus. Antiepileptic treatment is based on
      guidelines for treatment of overt status epilepticus and is started within 3
      hours after the diagnosis. If status epilepticus returns during tapering of
      sedative medication after suppression of all epileptiform activity for 2 * 24
      hours, it will be considered refractory. The primary outcome measure is
      neurological outcome defined as the Cerebral Performance Category (CPC) score at
      3 months, dichotomized into 'good' (CPC 1 to 2 = no or moderate neurological
      disability) and 'poor' (CPC 3 to 5 = severe disability, coma, or death).
      Secondary outcome measures include mortality and, for patients surviving up to 12
      months, cognitive functioning, health related quality of life, and depression.
      TRIAL REGISTRATION: Clinicaltrials.gov; NCT02056236. Date of registration: 4
      February 2014.

PMID- 25377068
TI  - An integrated assessment of habitat quality of national estuarine research
      reserves in the southeastern United States.
AB  - Multiple indicators of water quality, sediment quality, and biological condition
      were used to assess the status of ecological condition of National Estuarine
      Research Reserve System (NERRS) sites in North Carolina, South Carolina, and
      Georgia relative to a suite of corresponding scoring criteria. All measurements
      were made in subtidal aquatic habitats. Calculated scores were integrated into an
      overall index of habitat quality and used to make comparisons among the various
      NERR and nonNERR estuaries throughout the region. Sediment quality scores varied
      considerably among NERR sites, but in most cases were similar between individual
      NERR and non-NERR sites in corresponding states. Water quality and biological
      condition indicators scored consistently higher for NERRs versus non-NERR sites.
      Overall habitat quality scores also were consistently higher for NERRS sites,
      suggesting that these areas are on par with if not in slightly better condition
      ecologically than neighboring nonNERR estuaries. Portions of individual NERR
      sites rated as poor with respect to overall habitat quality were limited to
      relatively small areas (<13% of a reserve's total sampling area).

PMID- 25377069
TI  - Alternating magnetic field-induced hyperthermia increases iron oxide nanoparticle
      cell association/uptake and flux in blood-brain barrier models.
AB  - PURPOSE: Superparamagnetic iron oxide nanoparticles (IONPs) are being
      investigated for brain cancer therapy because alternating magnetic field (AMF)
      activates them to produce hyperthermia. For central nervous system applications,
      brain entry of diagnostic and therapeutic agents is usually essential. We
      hypothesized that AMF-induced hyperthermia significantly increases IONP blood
      brain barrier (BBB) association/uptake and flux. METHODS: Cross-linked
      nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated
      IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and
      citrate-IONP BBB cell association/uptake and flux were studied using two BBB
      Transwell((r)) models (bEnd.3 and MDCKII cells) after conventional and AMF
      induced hyperthermia exposure. RESULTS: AMF-induced hyperthermia for 0.5 h did
      not alter CNA-IONP size but accelerated citrate-IONP agglomeration. AMF-induced
      hyperthermia for 0.5 h enhanced CNA-IONP and citrate-IONP BBB cell
      association/uptake. It also enhanced the flux of CNA-IONPs across the two in
      vitro BBB models compared to conventional hyperthermia and normothermia, in the
      absence of cell death. Citrate-IONP flux was not observed under these conditions.
      AMF-induced hyperthermia also significantly enhanced paracellular pathway flux.
      The mechanism appears to involve more than the increased temperature surrounding
      the CNA-IONPs. CONCLUSIONS: Hyperthermia induced by AMF activation of CNA-IONPs
      has potential to increase the BBB permeability of therapeutics for the diagnosis
      and therapy of various brain diseases.

PMID- 25377071
TI  - Research priorities regarding multimodal peripheral nerve blocks for
      postoperative analgesia and anesthesia based on hospital quality data extracted
      from over 1,300 cases (2011-2014).

PMID- 25377072
TI  - Public health research in congenital heart disease.
AB  - Public health research is an integral part of the study of congenital heart
      disease. While this type of research has become more popular, particularly over
      the past decade, it has a history that stretches back to almost the beginnings of
      pediatric cardiology as a field. This review aims to introduce the concepts and
      methodologies of public health and how they relate to congenital heart disease,
      describe some of the challenges of traditional research methods in congenital
      heart disease, describe the history of public health research, and demonstrate
      the relevance of public health research, particularly databases, to pediatric
      cardiology fellows. 

PMID- 25377070
TI  - Induced pluripotent stem cells restore function in a human cell loss model of
      open-angle glaucoma.
AB  - Normally, trabecular meshwork (TM) and Schlemm's canal inner wall endothelial
      cells within the aqueous humor outflow pathway maintain intraocular pressure
      within a narrow safe range. Elevation in intraocular pressure, because of the
      loss of homeostatic regulation by these outflow pathway cells, is the primary
      risk factor for vision loss due to glaucomatous optic neuropathy. A notable
      feature associated with glaucoma is outflow pathway cell loss. Using controlled
      cell loss in ex vivo perfused human outflow pathway organ culture, we developed
      compelling experimental evidence that this level of cell loss compromises
      intraocular pressure homeostatic function. This function was restored by
      repopulation of the model with fresh TM cells. We then differentiated induced
      pluripotent stem cells (iPSCs) and used them to repopulate this cell depletion
      model. These differentiated cells (TM-like iPSCs) became similar to TM cells in
      both morphology and expression patterns. When transplanted, they were able to
      fully restore intraocular pressure homeostatic function. This successful
      transplantation of TM-like iPSCs establishes the conceptual feasibility of using
      autologous stem cells to restore intraocular pressure regulatory function in open
      angle glaucoma patients, providing a novel alternative treatment option.

PMID- 25377073
TI  - Quality of life measures in soft tissue sarcoma.
AB  - The assessment of health-related quality of life (HRQL) via patient-reported
      outcomes has the potential to answer critical questions and improve the care of
      soft tissue sarcoma (STS). This review outlines the rationale for quality of life
      measures in sarcoma, and details various instrument types: disease- and anatomic
      specific, provider-generated, generic HRQL and health state utilities. Prior
      usage in STS populations, relative advantages of specific patient-reported
      outcome measures and a framework for selecting appropriate measures are
      discussed. Uniform incorporation of validated HRQL measures in STS clinical
      research would further the understanding of patient wellbeing beyond traditional
      clinical measures, and more widespread use of health state utilities measures in
      particular has the potential to facilitate comparative effectiveness research. 

PMID- 25377074
TI  - Population pharmacokinetics of etomidate in neonates and infants with congenital
      heart disease.
AB  - BACKGROUND: Etomidate is a rapid-onset, short-acting hypnotic medication
      administered for the induction of anesthesia. It is currently approved by the
      Food and Drug Administration for use in older children and adults.
      Pharmacokinetic data to help guide dosing in neonates and infants are lacking.
      OBJECTIVE: The aim of this study was to determine the pharmacokinetics of
      etomidate in neonates and infants with congenital heart disease undergoing
      cardiac surgery. METHODS: Four neonates and 16 infants, postnatal age 0.3-11.7
      months, requiring open-heart surgery received 0.3 mg/kg of etomidate administered
      as a single intravenous dose prior to surgery. Blood sampling for plasma
      etomidate concentration occurred immediately following etomidate administration
      until the initiation of cardiopulmonary bypass. A population pharmacokinetic
      approach using nonlinear mixed-effects modeling was applied to characterize
      etomidate pharmacokinetics. RESULTS: The pharmacokinetics of etomidate was
      described by a two-compartment model with first-order elimination. An allometric
      weight-based model was applied to scale results to a 70 kg adult. Covariates
      including age and cardiac physiology were not found significantly to impact
      etomidate pharmacokinetics. The study population was found to have a central and
      intercompartmental clearance of 0.624 l/min/70 kg and 0.44 l/min/70 kg,
      respectively; central and peripheral distribution volume of 9.47 l/70 kgand 22.8
      l/70 kg, respectively. Inter-individual variability was 94-142% for all
      parameters and the residual variability was 29%. CONCLUSIONS: The clearance of
      etomidate is lower in neonates and infants with congenital heart disease compared
      with published values for older children without congenital heart disease. In
      addition, etomidate pharmacokinetics is highly variable in this pediatric cardiac
      population.

PMID- 25377075
TI  - Encapsulated-dye all-organic charged colored ink nanoparticles for
      electrophoretic image display.
AB  - Electrophoretic ink nanoparticles with high mobility are successfully fabricated
      by dispersion polymerization. The color of test cells can be changed by applying
      a bias voltage, as shown in the figure: the lower row shows the same cells as the
      upper row but with an applied voltage. These all-organic, encapsulated-dye,
      electrophoretic ink particles are expected to reduce the fabrication cost of e
      ink in electrophoretic image display cells. 

PMID- 25377076
TI  - Endothelin-a receptor antagonism after renal angioplasty enhances renal recovery
      in renovascular disease.
AB  - Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used
      to treat renal artery stenosis and renovascular disease (RVD); however, renal
      function is restored in less than one half of the cases. This study was designed
      to test a novel intervention that could refine PTRAS and enhance renal recovery
      in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD
      (induced by unilateral renal artery stenosis), established renal damage, and
      hypertension. Pigs with RVD then underwent PTRAS and were randomized into three
      groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade
      (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4
      weeks. Renal function was again evaluated after treatments, and then, ex vivo
      studies were performed on the stented kidney. PTRAS resolved renal stenosis,
      attenuated hypertension, and improved renal function but did not resolve renal
      microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy
      after PTRAS significantly improved hypertension, microvascular rarefaction, and
      renal injury and led to greater recovery of renal function. Conversely, combined
      ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS
      followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy
      could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD.
      These results also suggest that ET-B receptors are important for renal function
      in RVD and may contribute to recovery after PTRAS. Using clinically available
      compounds and techniques, our results could contribute to both refinement and
      design of new therapeutic strategies in chronic RVD. 

PMID- 25377077
TI  - Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated
      Rejection in Late Kidney Transplant Recipients.
AB  - The prevalent renal transplant population presents an opportunity to observe the
      adaptive changes in the alloimmune response over time, but such studies have been
      limited by uncertainties in the conventional biopsy diagnosis of T cell-mediated
      rejection (TCMR) and antibody-mediated rejection (ABMR). To circumvent these
      limitations, we used microarrays and conventional methods to investigate
      rejection in 703 unselected biopsies taken 3 days to 35 years post-transplant
      from North American and European centers. Using conventional methods, we
      diagnosed rejection in 205 biopsy specimens (28%): 67 pure TCMR, 110 pure ABMR,
      and 28 mixed (89 designated borderline). Using microarrays, we diagnosed
      rejection in 228 biopsy specimens (32%): 76 pure TCMR, 124 pure ABMR, and 28
      mixed (no borderline). Molecular assessment confirmed most conventional diagnoses
      (agreement was 90% for TCMR and 83% for ABMR) but revealed some errors,
      particularly in mixed rejection, and improved prediction of failure. ABMR was
      strongly associated with increased graft loss, but TCMR was not. ABMR became
      common in biopsy specimens obtained >1 year post-transplant and continued to
      appear in all subsequent intervals. TCMR was common early but progressively
      disappeared over time. In 108 biopsy specimens obtained 10.2-35 years post
      transplant, TCMR defined by molecular and conventional features was never
      observed. We conclude that the main cause of kidney transplant failure is ABMR,
      which can present even decades after transplantation. In contrast, TCMR
      disappears by 10 years post-transplant, implying that a state of partial adaptive
      tolerance emerges over time in the kidney transplant population. 

PMID- 25377078
TI  - Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation
      Chloride Transporters.
AB  - Upon activation by with-no-lysine kinases, STE20/SPS1-related proline-alanine
      rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such
      as the Na(+)-Cl(-) cotransporter (NCC) and Na(+)-K(+)-2Cl(-) cotransporter type 1
      (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating
      BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable
      and display hypotension with decreased activity (phosphorylation) of NCC and
      NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK
      activity could be a new class of antihypertensive drugs with dual actions (i.e.,
      NaCl diuresis and vasodilation). In this study, we developed a new ELISA-based
      screening system to find novel SPAK inhibitors and screened >20,000 small
      molecule compounds. Furthermore, we used a drug repositioning strategy to
      identify existing drugs that inhibit SPAK activity. As a result, we discovered
      one small-molecule compound (Stock 1S-14279) and an antiparasitic agent
      (Closantel) that inhibited SPAK-regulated phosphorylation and activation of NCC
      and NKCC1 in vitro and in mice. Notably, these compounds had structural
      similarity and inhibited SPAK in an ATP-insensitive manner. We propose that the
      two compounds found in this study may have great potential as novel
      antihypertensive drugs. 

PMID- 25377079
TI  - Midkine Regulates BP through Cytochrome P450-Derived Eicosanoids.
AB  - The effects of endothelium-derived hyperpolarizing factors have been attributed
      to cytochrome P450-derived epoxyeicosatrienoic acids (EETs), but the regulation
      and role of EETs in endothelial dysfunction remain largely unexplored.
      Hypertension is a primary risk factor for renal dysfunction, which is frequently
      accompanied by various systemic diseases induced by endothelial dysfunction in
      the microcirculation. We previously reported that the endothelial growth factor
      midkine (MK) enhances hypertension in a model of CKD. Here, we investigated the
      hypothesis that MK regulates EET activity and thereby BP. MK gene-deleted mice
      were resistant to hypertension and developed less glomerulosclerosis and
      proteinuria after administration of a nitric oxide synthase (NOS) inhibitor in
      the setting of uninephrectomy. The hypertension observed in uninephrectomized
      wild-type mice after NOS inhibition was ameliorated by anti-MK antibody. MK
      deficient mice produced higher amounts of EETs, and EETs dominantly regulated BP
      in these mice. Furthermore, MK administration to MK-deficient mice recapitulated
      the BP control observed in wild-type mice. EETs also dominantly regulated renal
      blood flow, which may influence renal function, in MK-deficient mice. Taken
      together, these results suggest that the MK/EET pathway is physiologically
      engaged in BP control and could be a target for the treatment of hypertension
      complicated by endothelial dysfunction.

PMID- 25377081
TI  - People who are transgender: mental health concerns.
AB  - ACCESSIBLE SUMMARY: The aim of the study was to elicit the views and opinions of
      transgender people in relation to mental health concerns. Four people who
      identified as transgender participated in semi-structured interviews. The main
      results showed that challenges existed for people around mental health issues.
      Mental health nurses can play a key role in the provision of psychosocial
      supports to transgender people and their families. Government policy makers are
      becoming increasingly interested in the views and experiences of people who
      utilize mental health services to inform rights-based and socially inclusive
      health and social care initiatives. However, very little information exists in
      the available literature about transgender people in this regard. The current
      research was part of a larger mixed methods study that used surveys and in-depth
      semi-structured interviews. This paper reports on the findings from the interview
      data that relate to the unique mental health experiences of the people whom
      identified as transgender (n = 4). The data were subject to thematic analysis,
      and the main themes that emerged included service experiences, treatment issues,
      other supports, and hopes and aspirations. Participants identified challenges and
      opportunities for enhancing mental health service provision for transgender
      people and their families. Some of the highlighted concerns related to
      practitioner attributes and relevant psychosocial supports. Mental health nurses
      are well placed to use their knowledge and therapeutic skills to support people
      who identify as transgender and significant people in their lives.

PMID- 25377080
TI  - Development of apixaban: a novel anticoagulant for prevention of stroke in
      patients with atrial fibrillation.
AB  - The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as
      alternatives to long-standing standards of care that include low-molecular-weight
      heparin and warfarin. The development of apixaban reflects a strategy to optimize
      the clinical pharmacology profile, dosing posology, trial designs, and
      statistical analyses across multiple indications, and to seek alignment with
      global health authorities. The primary objective of dose selection was to
      maintain balance between efficacy and bleeding risk. Twice-daily dosing of
      apixaban, rather than once daily, was chosen to lower peak concentrations and
      reduce fluctuations between peak and trough levels. Our discussion here focuses
      on the use of apixaban for stroke prevention in nonvalvular atrial fibrillation
      (NVAF). Supporting this indication, a pair of registrational trials was conducted
      that enrolled the full spectrum of patients who, by guidelines, were eligible for
      anticoagulation. In the AVERROES study of patients who were unsuitable for
      warfarin therapy, apixaban was superior to aspirin in reducing the risk of stroke
      or systemic embolism (SSE), without a significant increase in major bleeding
      (MB). In the ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic
      Events in Atrial Fibrillation) study, apixaban was superior to warfarin on the
      rates of SSE, MB, and all-cause mortality. Overall, these studies have
      demonstrated a substantially favorable benefit-risk profile for apixaban over
      warfarin and aspirin in NVAF. 

PMID- 25377082
TI  - Enhanced deacidification activity in Schizosaccharomyces pombe by genome
      shuffling.
AB  - A problem frequently occurring in making some kinds of wines, particularly Vitis
      quinquangularis Rehd wine, is the presence of malic acid at high concentrations,
      which is detrimental to the quality of wines. Thus, there is a need of the ways
      for effectively reducing the malic acid levels in wine. This study aimed to
      generate shuffled fusants of Schizosaccharomyces pombe with enhanced
      deacidification activity for reducing the excessive malic acid content in wine.
      Sz. pombe CGMCC 2.1628 was used as the original strain. The starting mutant
      population was generated by UV treatment. The mutants with higher deacidification
      activity were selected and subjected to recursive protoplast fusion. The
      resulting fusants were screened by using the indicator of malic acid
      concentration of fermentation supernatants on 96-well microtitre plates, measured
      with bromocresol green. After three rounds of genome shuffling, the best
      performing fusant, named GS3-1, was obtained. Its deacidification activity
      (consumed 4.78 g/l malic acid within 10 days) was increased by 225.2% as compared
      to that of original strain. In the Vitis quinquangularis Rehd wine fermentation
      test, GS3-1 consumed 4.0 g/l malic acid during the whole cycle of fermentation,
      providing up to 185.7% improvement in malic acid consumption compared with that
      of the original strain. This study shows that GS3-1 has great potential for
      improving the quality of Vitis quinquangularis Rehd wine.

PMID- 25377083
TI  - Population shuffling of protein conformations.
AB  - Motions play a vital role in the functions of many proteins. Discrete
      conformational transitions to excited states, happening on timescales of hundreds
      of microseconds, have been extensively characterized. On the other hand, the
      dynamics of the ground state are widely unexplored. Newly developed high-power
      relaxation dispersion experiments allow the detection of motions up to a one
      digit microsecond timescale. These experiments showed that side chains in the
      hydrophobic core as well as at protein-protein interaction surfaces of both
      ubiquitin and the third immunoglobulin binding domain of protein G move on the
      microsecond timescale. Both proteins exhibit plasticity to this microsecond
      motion through redistribution of the populations of their side-chain rotamers,
      which interconvert on the picosecond to nanosecond timescale, making it likely
      that this "population shuffling" process is a general mechanism. 

PMID- 25377084
TI  - Plant natural products: from traditional compounds to new emerging drugs in
      cancer therapy.
AB  - Natural products are chemical compounds or substances produced naturally by
      living organisms. With the development of modern technology, more and more plant
      extracts have been found to be useful to medical practice. Both micromolecules
      and macromolecules have been reported to have the ability to inhibit tumour
      progression, a novel weapon to fight cancer by targeting its 10 characteristic
      hallmarks. In this review, we focus on summarizing plant natural compounds and
      their derivatives with anti-tumour properties, into categories, according to
      their potential therapeutic strategies against different types of human cancer.
      Taken together, we present a well-grounded review of these properties, hoping to
      shed new light on discovery of novel anti-tumour therapeutic drugs from known
      plant natural sources. 

PMID- 25377085
TI  - Nimbolide inhibits invasion and migration, and down-regulates uPAR chemokine gene
      expression, in two breast cancer cell lines.
AB  - OBJECTIVES: Breast cancer is the most frequently diagnosed cancer and the leading
      cause of cancer death in women, worldwide. Urokinase type plasminogen activator
      (uPA) is a serine protease that is involved in cancer progression, especially
      invasion and metastasis of breast cancer. Nimbolide is a potent cytotoxic limnoid
      isolated from Azadirachta indica. Our previous studies have shown that nimbolide
      elicits pleiotropic effects on breast cancer cells; however, its roles in
      invasion and migration have not previously been fully elucidated. MATERIALS AND
      METHODS: Protein expression of pEGFR, VEGFR, NFkappaB, IKKalpha, IKKbeta, MMP-2,
      MMP-9 and TIMP-2 were analysed by western blotting. We also analysed expressions
      of uPA, uPAR genes and chemokines by real-time PCR. Breast cancer cell invasion
      was assessed by transwell invasion assay and cell migration analysed by scratch
      wound healing assay. RESULTS: Our results showed that reduced protein expression
      of pEGFR, VEGFR, NFkappaB, IKKalpha, beta, MMP-2, MMP-9 and TIMP-2 was higher in
      nimbolide-treated breast cancer cells. mRNA expression of uPA, uPAR, chemokines
      and their receptors were also significantly reduced in response to nimbolide
      treatment. Nimbolide inhibited breast cancer cell migration and invasion as shown
      in transwell invasion and wound healing assays. CONCLUSION: These results clearly
      proved inhibitory effects of nimbolide on tumour cell invasion and migration by
      down-regulating proteins critically involved in regulation of cell invasion and
      metastasis, suggesting a possible therapeutic role of nimbolide for breast
      cancer.

PMID- 25377086
TI  - Osmotic shrinkage elicits FAK- and Src phosphorylation and Src-dependent NKCC1
      activation in NIH3T3 cells.
AB  - The mechanisms linking cell volume sensing to volume regulation in mammalian
      cells remain incompletely understood. Here, we test the hypothesis that
      activation of nonreceptor tyrosine kinases Src, focal adhesion kinase (FAK), and
      Janus kinase-2 (Jak2) occurs after osmotic shrinkage of NIH3T3 fibroblasts and
      contributes to volume regulation by activation of NKCC1. FAK phosphorylation at
      Tyr397, Tyr576/577, and Tyr861 was increased rapidly after exposure to hypertonic
      (575 mOsm) saline, peaking after 10 (Tyr397, Tyr576/577) and 10-30 min (Tyr861).
      Shrinkage-induced Src family kinase autophosphorylation (pTyr416-Src) was induced
      after 2-10 min, and immunoprecipitation indicated that this reflected
      phosphorylation of Src itself, rather than Fyn and Yes. Phosphorylated Src and
      FAK partly colocalized with vinculin, a focal adhesion marker, after hypertonic
      shrinkage. The Src inhibitor pyrazolopyrimidine-2 (PP2, 10 MUM) essentially
      abolished shrinkage-induced FAK phosphorylation at Tyr576/577 and Tyr861, yet not
      at Tyr397, and inhibited shrinkage-induced NKCC1 activity by ~50%. The FAK
      inhibitor PF-573,228 augmented shrinkage-induced Src phosphorylation, and
      inhibited shrinkage-induced NKCC1 activity by ~15%. The apparent role of Src in
      NKCC1 activation did not reflect phosphorylation of myosin light chain kinase
      (MLC), which was unaffected by shrinkage and by PP2, but may involve Jak2, a
      known target of Src, which was rapidly activated by osmotic shrinkage and
      inhibited by PP2. Collectively, our findings suggest a major role for Src and
      possibly the Jak2 axis in shrinkage-activation of NKCC1 in NIH3T3 cells, whereas
      no evidence was found for major roles for FAK and MLC in this process. 

PMID- 25377087
TI  - CaV3.2 T-type Ca2+ channels in H2S-mediated hypoxic response of the carotid body.
AB  - Arterial blood O2 levels are detected by specialized sensory organs called
      carotid bodies. Voltage-gated Ca(2+) channels (VGCCs) are important for carotid
      body O2 sensing. Given that T-type VGCCs contribute to nociceptive sensation, we
      hypothesized that they participate in carotid body O2 sensing. The rat carotid
      body expresses high levels of mRNA encoding the alpha1H-subunit, and alpha1H
      protein is localized to glomus cells, the primary O2-sensing cells in the
      chemoreceptor tissue, suggesting that CaV3.2 is the major T-type VGCC isoform
      expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T
      type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca(2+)
      concentration, secretion of catecholamines from glomus cells, and sensory
      excitation of the rat carotid body. Similar results were obtained in the carotid
      body and glomus cells from CaV3.2 knockout (Cacna1h(-/-)) mice. Since
      cystathionine-gamma-lyase (CSE)-derived H2S is a critical mediator of the carotid
      body response to hypoxia, the role of T-type VGCCs in H2S-mediated O2 sensing was
      examined. Like hypoxia, NaHS, a H2S donor, increased intracellular Ca(2+)
      concentration and augmented carotid body sensory nerve activity in wild-type
      mice, and these effects were markedly attenuated in Cacna1h(-/-) mice. In wild
      type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve
      responses to hypoxia, and these effects were absent in CSE knockout mice. These
      results demonstrate that CaV3.2 T-type VGCCs contribute to the H2S-mediated
      carotid body response to hypoxia. 

PMID- 25377088
TI  - Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and
      induces ROS-mediated cardiomyocyte hypertrophy.
AB  - Recently, a locus at the mitochondrial exo/endonuclease EXOG gene, which has been
      implicated in mitochondrial DNA repair, was associated with cardiac function. The
      function of EXOG in cardiomyocytes is still elusive. Here we investigated the
      role of EXOG in mitochondrial function and hypertrophy in cardiomyocytes.
      Depletion of EXOG in primary neonatal rat ventricular cardiomyocytes (NRVCs)
      induced a marked increase in cardiomyocyte hypertrophy. Depletion of EXOG,
      however, did not result in loss of mitochondrial DNA integrity. Although EXOG
      depletion did not induce fetal gene expression and common hypertrophy pathways
      were not activated, a clear increase in ribosomal S6 phosphorylation was
      observed, which readily explains increased protein synthesis. With the use of a
      Seahorse flux analyzer, it was shown that the mitochondrial oxidative consumption
      rate (OCR) was increased 2.4-fold in EXOG-depleted NRVCs. Moreover, ATP-linked
      OCR was 5.2-fold higher. This increase was not explained by mitochondrial
      biogenesis or alterations in mitochondrial membrane potential. Western blotting
      confirmed normal levels of the oxidative phosphorylation (OXPHOS) complexes. The
      increased OCR was accompanied by a 5.4-fold increase in mitochondrial ROS levels.
      These increased ROS levels could be normalized with specific mitochondrial ROS
      scavengers (MitoTEMPO, mnSOD). Remarkably, scavenging of excess ROS strongly
      attenuated the hypertrophic response. In conclusion, loss of EXOG affects normal
      mitochondrial function resulting in increased mitochondrial respiration, excess
      ROS production, and cardiomyocyte hypertrophy. 

PMID- 25377089
TI  - Exendin-4 promotes endothelial barrier enhancement via PKA- and Epac1-dependent
      Rac1 activation.
AB  - Among emerging antidiabetic agents, glucagon-like peptide-1 (GLP-1)-based
      therapies carry special cardiovascular implications, exerting both direct and
      indirect effects. The control of vascular permeability is of pivotal importance
      in vascular pathologies. The objective of the present study was to determine the
      effect of GLP-1 on endothelial barrier function and assess the underlying
      mechanism(s). Here we show for the first time that the stable GLP-1 analog
      exendin-4 attenuated the leakage of subcutaneous blood vessels in mice indexed by
      dye extravasation caused by injections of thrombin. Moreover, in cultured
      endothelial cells, exendin-4 significantly prevented the thrombin-induced FITC
      dextran permeability of endothelial monolayers via GLP-1 receptor.
      Immunofluorescence microscopy reveals that exendin-4 abrogates detrimental
      effects of thrombin on VE-cadherin and the F-actin cytoskeleton, with decreased
      stress fiber and gap formation. Importantly, exendin-4 reduced thrombin-induced
      tyrosine phosphorylation of VE-cadherin at Y731 and Y658. Moreover, small GTPase
      Rac1 was significantly activated as a result of exendin-4 treatment. The efficacy
      of exendin-4 to counteract the barrier-compromising effect of thrombin was
      blunted when Rac1 was inactivated by Rac1 inhibitor NSC-23766. Inhibition of PKA
      activity or small-interfering RNA for exchange protein directly activated by cAMP
      1 (Epac1) decreased exendin-4-induced Rac1 activation and barrier enhancement,
      indicating the participation of both PKA and Epac1 in the barrier-stabilizing
      effect of exendin-4 elicited on thrombin-impaired barrier function. Thus, our
      findings have uncovered an unpredicted role for exendin-4 in the coordination of
      vascular permeability and clarified the molecular underpinnings that contribute
      to barrier restoration initiated by exendin-4. 

PMID- 25377090
TI  - Depressed excitability and ion currents linked to slow exocytotic fusion pore in
      chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.
AB  - Altered synaptic transmission with excess glutamate release has been implicated
      in the loss of motoneurons occurring in amyotrophic lateral sclerosis (ALS).
      Hyperexcitability or hypoexcitability of motoneurons from mice carrying the ALS
      mutation SOD1(G93A) (mSOD1) has also been reported. Here we have investigated the
      excitability, the ion currents, and the kinetics of the exocytotic fusion pore in
      chromaffin cells from postnatal day 90 to postnatal day 130 mSOD1 mice, when
      motor deficits are already established. With respect to wild-type (WT), mSOD1
      chromaffin cells had a decrease in the following parameters: 95% in spontaneous
      action potentials, 70% in nicotinic current for acetylcholine (ACh), 35% in Na(+)
      current, 40% in Ca(2+)-dependent K(+) current, and 53% in voltage-dependent K(+)
      current. Ca(2+) current was increased by 37%, but the ACh-evoked elevation of
      cytosolic Ca(2+) was unchanged. Single exocytotic spike events triggered by ACh
      had the following differences (mSOD1 vs. WT): 36% lower rise rate, 60% higher
      decay time, 51% higher half-width, 13% lower amplitude, and 61% higher quantal
      size. The expression of the alpha3-subtype of nicotinic receptors and proteins of
      the exocytotic machinery was unchanged in the brain and adrenal medulla of mSOD1,
      with respect to WT mice. A slower fusion pore opening, expansion, and closure are
      likely linked to the pronounced reduction in cell excitability and in the ion
      currents driving action potentials in mSOD1, compared with WT chromaffin cells.

PMID- 25377091
TI  - Loss of NHE8 expression impairs ocular surface function in mice.
AB  - Sodium/hydrogen exchanger (NHE) 8 is expressed at the apical membrane of the
      epithelial cells and plays important roles in neutral sodium absorption in the
      gastrointestinal tract and the kidney. It also has an important role in
      epithelial mucosal protection in the gastric gland and the intestine. Although
      NHE8 has broad tissue distribution, the precise location and the physiological
      role of NHE8 in the eye remain unknown. In the present study, we successfully
      detected the expression of NHE8 in the ocular surface by PCR and Western blot in
      human and mouse eyes. Immunohistochemistry staining located NHE8 protein at the
      plasma membrane of the epithelial cells in the conjunctiva, the cornea, and the
      lacrimal gland both in human and mouse. We also detected the expression of
      downregulated-in-adenoma (DRA, a Cl(-)/HCO3 (-) transporter) in the ocular
      surface epithelial cells. Using NHE8-/- mouse model, we found that loss of NHE8
      function resulted in reduced tear production and increased corneal staining.
      These NHE8-/- mice also showed increased expression of TNF-alpha and matrix
      metalloproteinase 9 (MMP9) genes. The expression of epithelial keratinization
      marker genes, small proline-rich protein 2h (Sprr2h) and transglutaminase 1
      (Tgm1), were also increased in NHE8-/- eyes. Furthermore, DRA expression in NHE8
      /- mice was reduced in the conjunctiva, the cornea, and the lacrimal glands in
      association with a reduction in conjunctival mucosal pH. Altered ocular surface
      function and reduced epithelial DRA expression in NHE8-/- mice suggest that the
      role of NHE8 in ocular surface tissue involve in tear production and ocular
      epithelial protection. This study reveals a potential novel mechanism of dry eye
      condition involving abnormal NHE8 function. 

PMID- 25377092
TI  - Changes in velocity profile according to blood viscosity in a microchannel.
AB  - Red blood cells (RBCs) are important to dictate hemorheological properties of
      blood. The shear-thinning effect of blood is mainly attributed to the
      characteristics of the RBCs. Variations in hemorheological properties alter flow
      resistance and wall shear stress in blood vessels. Therefore, detailed
      understanding of the relationship between the hemorheological and hemodynamic
      properties is of great importance. In this study, blood viscosity and blood flow
      were simultaneously measured in the same microfluidic device by monitoring the
      flow-switching phenomenon. To investigate blood flows according to
      hemorheological variations, the flow rate of blood samples (RBCs suspended in
      autologous plasma, dextran-treated plasma, and in phosphate buffered saline
      solution) was precisely controlled with a syringe pump. Velocity profiles of
      blood flows were measured by using a micro-particle imagevelocimetry technique.
      The shape of velocity profiles was quantified by using a curve-fitting equation.
      It is found that the shape of the velocity profiles is highly correlated with
      blood viscosity. To demonstrate the relationship under ex vivo conditions,
      biophysical properties and velocity profiles were measured in an extracorporeal
      rat bypass loop. Experimental results show that increased blood viscosity seems
      to induce blunt velocity profile with high velocity component at the wall of the
      microchannel. Simultaneous measurement of blood viscosity and velocity profile
      would be useful for understanding the effects of hemorheological features on the
      hemodynamic characteristics in capillary blood vessels. 

PMID- 25377093
TI  - Bilateral reconstructive costoplasty for razorback deformity correction in
      adolescent idiopathic scoliosis.
AB  - BACKGROUND: Correcting the chest wall deformity is an important goal of scoliosis
      surgery. A prominent rib hump deformity may not be adequately addressed by
      scoliosis correction alone. It has been shown that costoplasty in conjugation
      with scoliosis correction and instrumented spinal fusion is superior to spinal
      fusion alone in addressing the chest wall deformity. In cases of severe rib hump
      deformity unilateral convex side costoplasty alone might not adequately restore
      thoracic cage symmetry necessitating for additional concave side rib cage
      reconstruction. CASE REPORT: A 16-year-old male with adolescent idiopathic
      scoliosis and a sharp, cosmetically unacceptable, prominent rib hump (razorback
      deformity) underwent scoliosis correction with posterior spinal fusion and
      bilateral costoplasty. The convex-sided ribs were resected and used for concave
      sided rib reconstruction. The rib hump height was reduced from 70 mm before the
      procedure to 10 mm after the procedure and the apical trunk rotation was reduced
      from 36 degrees  to 5 degrees , respectively. Solid spinal fusion and ribs union
      was achieved. The patient remained very satisfied with no loss of correction at 2
      year postoperative follow-up. CONCLUSION: Bilateral costoplasty in conjugation
      with scoliosis correction may provide a safe and effective method for the
      treatment of severe rib cage deformities associated with thoracic scoliosis. It
      should be considered in the presence of prominent rib hump deformity, where
      scoliosis correction alone or with unilateral costoplasty is unlikely to provide
      adequate correction.

PMID- 25377094
TI  - A case of severe and rigid congenital thoracolumbar lordoscoliosis with
      diastematomyelia presenting with type 2 respiratory failure: managed by staged
      correction with controlled axial traction.
AB  - INTRODUCTION: Congenital lordoscoliosis is an uncommon pathology and its
      management poses formidable challenge especially in the presence of type 2
      respiratory failure and intraspinal anomalies. In such patients standard
      management protocols are not applicable and may require multistage procedure to
      minimize risk and optimize results. CASE DESCRIPTION: A 15-year-old girl
      presented in our hospital emergency services with severe breathing difficulty.
      She had a severe and rapidly progressing deformity in her back, noted since 6
      years of age, associated with severe respiratory distress requiring oxygen and
      BiPAP support. She was diagnosed to have a severe and rigid congenital right
      thoracolumbar lordoscoliosis (coronal Cobb's angle: 105 degrees  and thoracic
      lordosis -10 degrees ) with type 1 split cord malformation with bony septum
      extending from T11 to L3. This leads to presentation of restrictive lung disease
      with type 2 respiratory failure. As her lung condition did not allow for any
      major procedure, we did a staged procedure rather than executing in a single
      stage. Controlled axial traction by halogravity was applied initially followed by
      halo-femoral traction. Four weeks later, this was replaced by halo-pelvic
      distraction device after a posterior release procedure with asymmetric pedicle
      substraction osteotomies at T7 and T10. Halo-pelvic distraction continued for 4
      more weeks to optimize and correct the deformity. Subsequently definitive
      posterior stabilization and fusion was done. The detrimental effect of
      diastematomyelia resection in such cases is clearly evident from literature, so
      it was left unresected. A good scoliotic correction with improved respiratory
      function was achieved. Three years follow-up showed no loss of deformity
      correction, no evidence of pseudarthrosis and a good clinical outcome with
      reasonably balanced spine. CONCLUSION: The management of severe and rigid
      congenital lordoscoliotic deformities with intraspinal anomalies is challenging.
      Progressive reduction in respiratory volume in untreated cases can lead to acute
      respiratory failure. Such patients have a high rate of intraoperative and
      postoperative morbidity and mortality. Hence a staged procedure is recommended.
      Initially a less invasive procedure like halo traction helps to improve their
      respiratory function with simultaneous correction of the deformity, while
      allowing for monitoring of neurological deficit. Subsequently spinal osteotomies
      and combined halo traction helps further improve the correction, following which
      definitive instrumented fusion can be done.

PMID- 25377095
TI  - Person-centred care: clarifying the concept in the context of inpatient
      psychiatry.
AB  - This paper reports an analysis of the concept of person-centred care in the
      context of inpatient psychiatry. It has been suggested that person-centred care
      in inpatient psychiatry might differ from person-centred care in other contexts,
      indicating a need to clarify the concept in this specific context. Scholarly
      papers from health-related disciplines were identified following a systematic
      search of the electronic databases CINAHL, PUBMED and PsycINFO, covering records
      indexed up until March 2014. An evolutionary approach to concept analysis was
      applied, integrating principles for data extraction and analysis in integrative
      reviews. The concept of person-centred care was defined as cultural, relational
      and recovery-oriented. It aspires to improve care and calls for a transformation
      of inpatient psychiatry. The concept is closely related to the concepts of
      recovery and interpersonal nursing. The result is described in terms of
      attributes, antecedents, consequences and related concepts. It is concluded that
      the further development of the concept needs to consider the contexts of the
      concept at both conceptual and praxis levels. Further research should explore the
      nature of and relationships between context, culture, care practice and outcomes
      in inpatient psychiatry from a perspective of person-centred care. The results of
      this analysis can provide a framework for such research. 

PMID- 25377096
TI  - Impact of colorectal cancer diagnosis and treatment on health-related quality of
      life among older Americans: a population-based, case-control study.
AB  - BACKGROUND: Data on health-related quality of life (HRQoL) changes among
      Americans aged >=65 following colorectal cancer (CRC) diagnosis and treatment are
      limited. This study compared HRQoL changes among CRC patients across stages from
      before to after diagnosis with matched noncancer controls. METHODS: This
      population-based study used the Surveillance, Epidemiology, and End Results
      Medicare Health Outcomes Survey (MHOS) data set (1998-2007). Medicare Advantage
      beneficiaries diagnosed with CRC between their baseline and follow-up MHOS (n =
      349) were matched to noncancer controls (n = 1745) using propensity scores. Mixed
      effects analysis of covariance models estimated changes in HRQoL (measured by the
      Medical Outcomes Study Short Form-36/Veterans RAND 12-item Survey) and the
      ability to perform 6 activities of daily living (ADLs) between baseline and
      follow-up. Logistic regression models estimated odds ratios for ADL impairments
      and major depressive disorder (MDD) risk. RESULTS: Mean time between CRC
      diagnosis and follow-up MHOS was 12.3 +/- 9.8 months. Compared with controls, CRC
      patients had significantly lower scores in all physical and mental health domains
      at follow-up. The greatest decrements were observed in physical health and were
      largely driven by declines in the 6 months postdiagnosis and in stage III and IV
      patients. At follow-up, CRC patients had greater overall ADL impairment and
      difficulty with dressing, eating, and getting in/out of chairs. CRC patients,
      particularly stage IV patients, had greater odds of being at risk for MDD
      relative to controls. CONCLUSIONS: This study further underscores the adverse
      effects of CRC on physical health and the need to support older Americans' basic
      self-care needs, with attention to later-stage patients' increased debility.

PMID- 25377097
TI  - Context for practice: living with incontinence or an indwelling catheter.

PMID- 25377098
TI  - Development of a high fecal output algorithm.

PMID- 25377099
TI  - Improvements to public facilities for persons with ostomies.

PMID- 25377100
TI  - Improvements to ostomate facilities.

PMID- 25377101
TI  - Skin care product evaluation in a group of critically ill, premature neonates: a
      descriptive study.
AB  - PURPOSE: Cleansing, moisturizing, and protecting neonatal skin is important, but
      literature evaluating specific product lines is limited. The purpose of this
      study was to measure the influence of a skin care product line on overall skin
      condition, perineal erythema, and pain when applied to neonates in a neonatal
      intensive care unit (NICU). DESIGN: This was an open label, descriptive study.
      Comparisons were made between measurements taken at the beginning of the study to
      those at the end, on the same subjects. SUBJECTS AND SETTING: The study was
      conducted in a 41-bed NICU at Driscoll Children's Hospital in Corpus Christi,
      Texas, that serves 31 counties in the region. This NICU treats children needing
      level 2 and 3 care, with a 1:1 or 2:1 nurse staffing ratio. This is not a
      birthing center; patients come from other community hospitals. Twenty-nine
      neonates participated in the study; their average body weight was 1.39 kg (3.06
      lb) and their average gestation was 31.7 weeks. METHODS: A skin care product line
      was introduced into a neonatal intensive care unit for 14 days. The products
      included 2 cleansers, 2 moisturizers, and a skin protectant with zinc oxide.
      Three outcome measures were tracked: Neonatal Skin Condition Score (NSCS), Skin
      Erythema Scale (SES), and pain. Nurses were also given a product evaluation
      survey. Descriptive statistics were used to report percentages and trends. Paired
      t tests were used to compare the mean NSCS, SES, and pain scores from the first 2
      days a subject was in the study to the mean of the scores from the last 2 days
      they were in the study. RESULTS: Subjects experienced approximately 1774
      exposures to individual products during data collection. No differences were
      found in pain scores (P = .132), SES score (P = .059), or NSCS (P = .603) when
      mean values were compared at the beginning and end of the study. Analysis of the
      product evaluation survey for questions on cleaning, moisturizing, and reducing
      discomfort found that more than 90% of nurses ranked the new products as better
      than or equal to similar products used previously. CONCLUSIONS: Use of a skin
      care product line was not associated with significant increases in overall
      neonatal skin condition measured with the NSCS, perineal erythema measured with
      the SES, or pain. The nurses caring for the subjects in this study prefer these
      products to others they have used in the past.

PMID- 25377102
TI  - Patient perceptions of the role of nutrition for pressure ulcer prevention in
      hospital: an interpretive study.
AB  - PURPOSE: The aims of this study were to explore (a) patients' perceptions of the
      role of nutrition in pressure ulcer prevention; and (b) patients' experiences
      with dieticians in the hospital setting. DESIGN: Interpretive qualitative study.
      SUBJECTS AND SETTING: The sample comprised 13 females and 7 males. Their mean age
      was 61.3 +/- 12.6 years (mean +/- SD), and their average hospital length of stay
      was 7.4 +/- 13.0 days. The research setting was a public health hospital in
      Australia. METHODS: In this interpretive study, adult medical patients at risk of
      pressure ulcers due to restricted mobility participated in a 20 to 30 minute
      interview using a semi-structured interview guide. Interview questions were
      grouped into 2 domains; perceptions on the role of nutrition for pressure ulcer
      prevention; and experiences with dieticians. Recorded interviews were transcribed
      and analyzed using content analysis. RESULTS: Within the first domain, 'patient
      knowledge of nutrition in pressure ulcer prevention,' there were varying patient
      understandings of the role of nutrition for prevention of pressure ulcers. This
      is reflected in 5 themes: (1) recognizing the role of diet in pressure ulcer
      prevention; (2) promoting skin health with good nutrition; (3) understanding the
      relationship between nutrition and health; (4) lacking insight into the role of
      nutrition in pressure ulcer prevention; and (5) acknowledging other risk factors
      for pressure ulcers. Within the second domain, patients described their
      experiences with and perceptions on dieticians. Two themes emerged, which
      expressed differing opinions around the role and reputation of dieticians; they
      were receptive of dietician input; and displaying ambivalence towards dieticians'
      advice. CONCLUSIONS: Hospital patients at risk for pressure ulcer development
      have variable knowledge of the preventive role of nutrition. Patients had
      differing perceptions of the importance and value of information provided by
      dieticians.

PMID- 25377103
TI  - Use of the Braden Scale for pressure ulcer risk assessment in a community
      hospital setting: the role of total score and individual subscale scores in
      triggering preventive interventions.
AB  - PURPOSE: To determine whether pressure ulcer preventive interventions are
      implemented when a total Braden Scale score reflects that the patient is at risk.
      DESIGN: A retrospective chart review was completed for 20 patients with confirmed
      hospital-acquired pressure ulcers (HAPUs). SUBJECTS AND SETTING: A convenience
      sample of 20 patients with HAPUs confirmed by a certified wound nurse was
      systematically selected from 63 charts. The study setting was a 200-bed acute
      care facility in the Midwestern United States. METHODS: A retrospective review of
      20 patient charts was conducted. Data collected included daily Braden Scale
      scores and subscale scores, along with pressure ulcer preventive intervention
      implementation for at-risk (cumulative Braden Scale scores <= 18) and not-at-risk
      (cumulative Braden Scale scores > 18) days. Data were collected both before and
      after pressure ulcer occurrence. The occurrence of preventive interventions was
      compared between at-risk and not-at-risk patient days. RESULTS: Nineteen percent
      of not-at-risk patient days were found to have lower subscale scores, indicating
      a need for focused preventive interventions. The day before an HAPU occurred, the
      mean Braden Scale score was 13.7 +/- 2.8 (mean +/- SD) for those who were
      provided an intervention and 18.5 +/- 2.3 for those not provided an intervention
      (t = 3.89, P = .001). Sixty-three percent of at-risk patients received some
      intervention the day before an HAPU occurred, while 20% of not-at-risk patients
      received some intervention. CONCLUSIONS: Routine use of a pressure ulcer risk
      assessment tool is considered necessary for a comprehensive pressure ulcer
      prevention program. Planning preventive care according to the subscale scores of
      the Braden Scale may be more effective for prevention of HAPUs in some cases.

PMID- 25377104
TI  - Developing a wound and skin care program.
AB  - The purpose of this article is to review the process used in a large Veterans
      Affairs facility to unite a group of diverse wound care specialists together into
      a coordinated program. Program development is an iterative, interactive process
      requiring continued recycling of efforts until projects are completed. The
      Program Development Cycle is presented as an example of intentional planning that
      has been divided into 4 phases: (1) identifying the agency culture, (2) engaging
      in targeted project development, (3) developing operational strategies, and (4)
      conducting follow-up analysis. Specific examples of developing a mission, program
      goals, and wound care champions are discussed. Discussion also incorporates
      suggestions for changing organizational culture, developing policies and
      procedures, using best practices and guidelines, creating a wound fair, and
      incorporating a skin bundle and the challenges of outcome assessment.

PMID- 25377105
TI  - Education project to improve venous stasis self-management knowledge.
AB  - PURPOSE: The purpose of this study was to evaluate patients' knowledge of chronic
      venous disease, venous ulcer occurrence and recurrence, and self-care at
      baseline, immediately following, 2, and 9 weeks after an educational
      intervention. SUBJECTS AND SETTING: The study sample comprised 30 patients
      diagnosed with venous ulcers. The research setting was an outpatient facility
      specializing in wound care located in South Florida; the educational intervention
      occurred in subjects' homes. DESIGN: Single group before and after intervention
      research design. METHODS: Patients diagnosed with a first-time venous ulcer were
      assessed regarding their disease and self-care knowledge. Assessments were
      completed at baseline, immediately following an educational intervention, and
      during 2- and 9-week follow-up home visits. In addition to evaluating patient
      knowledge, wound healing (evaluated by the treating nurse or reported by the
      patient) was assessed at 2- and 9-week follow-up and wound recurrence was
      assessed at 9-week follow-up. RESULTS: The educational intervention resulted in a
      statistically significant increase in knowledge scores (P = .002). This change
      persisted when patients were evaluated during 2- and 9-week follow-up visits (P =
      .003). In addition, half of patients who completed the educational intervention
      remained free of recurrence when evaluated at 9 weeks. CONCLUSION: Results
      suggest that patient education related to venous ulcers improves knowledge
      regarding the disease process and self-care and reduces recurrence when measured
      at 9 weeks postintervention.

PMID- 25377106
TI  - Staff nurse confidence in their skills and knowledge and barriers to caring for
      patients with ostomies.
AB  - PURPOSE: Patients with ostomies often state that staff nurses display a lack of
      confidence in knowledge and skills related to ostomy care. This study examined
      the confidence and perceptions of barriers among hospital staff nurses when
      caring for ostomy patients. DESIGN: Descriptive, cross-sectional study. SUBJECTS
      AND SETTING: A convenience sample of 576 staff nurses, including 510 registered,
      61 licensed practical, and 5 unspecified nurses, participated in the study. The
      study sample practiced at 3 sites: an academic medical center, a Veteran's
      Administration Center, and a not-for-profit hospital in the state of New York.
      METHODS: Links to a 17-question electronic survey were distributed by e-mail. The
      survey included items that queried demographics, availability of an ostomy nurse,
      ostomy training in school, and frequency of care of ostomy patients. Participants
      also responded to 22 statements using a 6-point Likert Scale (1 = Strongly
      Disagree, 6 = Strongly Agree). These statements queried confidence in providing
      ostomy care and perceived barriers. RESULTS: Higher confidence in ostomy care
      knowledge (k) and skills (s) was associated with being an LPN (P < .0001 [k], P =
      .003 [s]), years of nursing experience (P = .009 [k], P = .01 [s]), having ostomy
      training (P = .002 [k], P = .02 [s]), frequency of providing ostomy care (P <
      .0001 for each), and knowing how to obtain and use ostomy supplies (P < .0001 for
      each). The highest reported confidence was associated with emptying a pouch (mean
      +/- SD, 5.32 +/- 0.91), and the lowest was knowledge of nutrition for persons
      with ostomies (3.96 +/- 1.21). Almost 1 in 5 respondents (18.6%) was unaware that
      a certified ostomy nurse practiced at their institution. CONCLUSION: Confidence
      of staff nurses in delivering ostomy care was higher with training and
      experience. Opportunities for continuing education may increase staff nurse
      confidence in providing ostomy care. The greatest barrier was lack of knowledge
      about the presence of an ostomy nurse as a resource in caring for patients.

PMID- 25377107
TI  - Bridging the gap: perceived educational needs in the inpatient to home care
      setting for the person with a new ostomy.
AB  - PURPOSE: The purpose of this study was to investigate what specific ostomy self
      care educational content is considered the most useful by the new ostomy patient
      after discharge. DESIGN: A cross-sectional, correlational design was used to
      address study aims. SUBJECTS AND SETTING: The sample comprised 33 men and 27
      women with a mean age of 55.58 +/- 15.56 (mean +/- SD) years, range 27 to 79
      years old. The study setting was a 587-bed teaching hospital, level 1 trauma
      center in the Midwest, with Magnet designation. METHODS: Demographic data were
      collected during the patients' hospital stay as part of routine care. This
      information is used for follow-up with all ostomy patients who have surgery in
      this hospital. All of the participants in this study completed an interview
      administered by phone or in person. A semistructured interview guide was used to
      elicit participant perceptions of the usefulness of 4 categories of ostomy care,
      including (1) ostomy information (ostomy function), (2) activities of daily
      living (strategies to manage travel, bathing, intimacy, odor), (3) ostomy care
      (strategies for managing the ostomy), and (4) other informational needs (social
      support resources). Participants were asked to rate these 4 areas from most
      useful to least useful, using a 4-point scale. At the end of the interview,
      participants were asked, "Has there been anything that has happened or event
      related to your ostomy that your ostomy teaching did not prepare you for?" The
      interview took place several weeks after surgery or during their readmission
      visit for surgical ostomy takedown. RESULTS: Sixty-two patients were enrolled
      into the study, and 60 participants completed the data collection. The sample
      included 26 (43%) patients with ileostomies, 18 (30%) with colostomies, and 16
      (27%) with urostomies. Ninety percent ranked the education category of ostomy
      self-care as the most useful content, 55% ranked information on resuming
      activities of daily living as the second most useful category, and 55% ranked
      general information as third most useful content area. Fifty respondents (83%)
      ranked ostomy support as the least useful. Nine (15%) of the participants felt
      unprepared for their first pouch leak, and 2 (3%) reported difficulty adjusting
      to the feel of the stool entering the pouch. Two patients would have liked more
      photos of peristomal skin conditions and how to treat them. CONCLUSIONS: Since
      the category of ostomy self-care ranked highest, patient teaching for the new
      ostomy patient should focus on this skill set, including stoma care, how, and
      when to empty and change the pouch.

PMID- 25377108
TI  - Exploration of health status, illness perceptions, coping strategies, and
      psychological morbidity in stoma patients.
AB  - PURPOSE: We employed the Common Sense Model (CSM) of illness perceptions to
      examine the relative contribution of illness perceptions, stoma self-efficacy,
      and coping strategies in explaining anxiety and depression symptoms in patients
      with a fecal ostomy. The CSM suggests that the consequences of illness activity,
      such as psychological distress, are influenced by an individual's illness
      perceptions as well as what coping strategies they engage in. DESIGN:
      Descriptive, cross-sectional questionnaire-based study. SUBJECTS AND SETTING: One
      hundred fifty adults with a stoma (54 males, and 96 females; mean age 44 years)
      completed an online survey. METHODS: Several instruments were used to measure
      study outcomes, including the Health Perceptions Questionnaire, Brief Illness
      Perceptions Questionnaire, Carver Brief Coping Questionnaire, Stoma Self-Efficacy
      Scale, and the Hospital Anxiety and Depression Scale. Participants were advised
      of the study through online forums containing a link to the survey. Outcome
      measures used in the current study are valid and reliable and have been
      extensively used in medically ill patients. RESULTS: Using structural equation
      modeling, the final model provided an excellent fit to the data (chi23= 16.53, P
      = .22, chi/N = 1.27, SRMR < 0.03, RMSEA < 0.05, GFI > 0.97, CFI > 0.99). There
      was a direct pathway from health status to illness perceptions months since
      surgery directly influenced health status, illness beliefs, and adaptive emotion
      focused coping (beta= .81, P < .001). Several indirect (mediating) pathways were
      also identified. Illness perceptions mediated the relationship between health
      status and stoma self-efficacy and maladaptive and adaptive emotion-focused
      coping. Maladaptive coping mediated the relationship between illness perceptions
      and depression and anxiety, and adaptive emotion-focused coping mediated the
      relationship between illness perception and depression. The final model provided
      support for the CSM, in that illness perceptions were directly related to illness
      status, and that both illness perceptions and coping strategies directly
      influenced anxiety and depression. More specifically, maladaptive coping style
      (eg, ignore problems) exacerbated depression and anxiety symptoms, while self
      efficacy and emotion-focused coping style (eg, seek advice) ameliorate
      depression, but not anxiety. Months since surgery was associated with improved
      health status, reduced poorer illness perceptions, and increased emotional
      focused coping. CONCLUSIONS: Illness perceptions and coping were found to mediate
      anxiety and depression. The results confirm that how individuals perceive their
      illness and what coping strategies they engage in impacts their psychological
      well-being. Study findings support the need for designing targeting psychological
      interventions based on individual illness perceptions and self-efficacy rather
      than exclusively focusing on coping strategies in patients with a stoma.

PMID- 25377109
TI  - The influence of social support from the family on health related-quality of life
      in persons with a colostomy.
AB  - PURPOSE: We evaluated the influence of social support on health-related quality
      of life (HRQOL) in persons with a colostomy, taking into account time since
      surgery. SUBJECTS AND SETTINGS: The study was conducted in 8 cities in Poland.
      The sample comprised 128 patients with a colostomy; their mean age was 66.24
      years. Forty-five percent of participants had lived with a colostomy for more
      than 5 years, and 16% had a colostomy for less than 1 year. INSTRUMENTS: The
      questionnaire used in the study included 76 questions divided into 3 parts. The
      first part comprised 8 questions that queried demographic characteristics. Parts
      2 and 3 included 2 validated scales assessing HRQOL and social support,
      respectively. Health-related quality of life was assessed using the Functional
      Assessment of Cancer Therapy-Colorectal instrument. Social support received was
      assessed using the Berlin Social Support Scale. In the case of both scales, the
      respondents were asked to assess their status during the last 7 days. METHODS:
      The study was conducted by an interviewer during monthly meetings of colostomy
      support groups as well as during hospitalization. The respondents gave their
      verbal answers to questions read by the interviewer or completed the
      questionnaires by themselves. After the questionnaire was completed, the
      interviewer verified completeness of answers. The outcome time elapsed since
      surgery was categorized as 3 subgroups: (1) respondents having a colostomy 1 year
      or less, (2) respondents having colostomy for more than 1 or up to 5 years, and
      (3) respondents having colostomy more than 5 years. RESULTS: Analysis revealed a
      statistically significant relationship between level of social support and HRQOL
      among persons with a colostomy (R = 0.361, P = .000029). Moreover, we observed
      that the time elapsed since colostomy surgery influenced this relationship. Level
      of social support and HRQOL were not significantly related in persons living with
      a colostomy <=1 year (R = 0.155, P = .525). The correlation was significant in
      persons with a colostomy for more than 1 to but less than 5 years (R = 0.329, P =
      .02), and in individuals living with a colostomy for more than 5 years (R =
      0.482, P = .0001). CONCLUSIONS: Persons with permanent colostomies and the higher
      level of social support from family reported higher HRQOL than did persons with
      lower levels of social support. Time elapsed since colostomy surgery exerts a
      positive effect on this relationship; the longer the patients live with a
      colostomy, the greater the influence of social support.

PMID- 25377110
TI  - A qualitative analysis of individual and family caregiver responses to the impact
      of urinary incontinence on quality of life.
AB  - PURPOSE: The purpose of the original mixed-design study was to compare affected
      individual and family caregiver perceptions of urinary incontinence quality of
      life in relation to their empathic responses toward one another and to explore
      their qualitative responses of factors that hinder or facilitate these responses.
      The aim of this secondary analysis is to report responses shared by affected
      individuals and family caregivers on how their lives have been impacted by
      urinary incontinence. DESIGN: Qualitative study with content analysis. SUBJECTS
      AND SETTING: The sample comprised 13 persons with urinary incontinence and 13
      family caregivers. Their mean age was 78 years and the mean age for caregivers
      was 67 years. Caregivers were mainly the spouses or daughters of affected
      respondents. Interviews were conducted in participants' homes in Winnipeg,
      Manitoba, Canada. METHODS: Data were collected via 26 audio-recorded interviews.
      Content analysis was used to capture major themes arising from the data. RESULTS:
      Five major themes with respective subthemes highlight how urinary incontinence
      influenced the quality of life of affected individuals and their family
      caregivers, including (1) life changes, (2) psychological responses and coping,
      (3) painful responses of others, (4) reticence to seek medical attention, and (5)
      advice to health care professionals. CONCLUSIONS: Health care professionals
      should recognize that dealing with urinary incontinence in the home is a "team
      effort" between affected individuals and family caregivers. Educational efforts
      need to counter attitudes in care providers who avoid talking about urinary
      continence and enhance sensitivities toward affected individuals' and family
      caregivers' ongoing need for control in continence care based on their unique
      needs and preferences.

PMID- 25377111
TI  - Pad weighing for reduction of indwelling urinary use and catheter-associated
      urinary tract infection: a quality improvement project.
AB  - Catheter-associated urinary tract infections pose a significant risk to
      hospitalized patients. Measuring accurate urinary output is a common reason for
      indwelling catheterizations in acutely ill patients. The risk of catheter
      associated infections may be eliminated while maintaining ability to measure
      urinary output of incontinent patients through the use of a highly absorbent pad
      and weighing postincontinence. The dry pad weight is subtracted from the wet pad
      weight and the resulting difference (expressed in grams) equals the volume of
      urine leaked into the pad in milliliters. We found that using this system of
      improved measurement of urine output when compared to documenting the number of
      incontinent episodes while allowing removal of indwelling urethral catheters as
      soon as possible. 

PMID- 25377112
TI  - Using distributed practice to prepare for the foot care exam.

PMID- 25377113
TI  - Wound healing, angiotensin-converting enzyme inhibition, and collagen-containing
      products: a case study.
AB  - BACKGROUND: The effects of multiple medications may impair or enhance wound
      healing. A review of the literature for drug side effects identified cell culture
      and case studies of angiotensin-converting enzyme inhibitors (ACEIs) impairing
      collagen deposition in cutaneous wounds; these medications have also been used to
      prevent or minimize keloid formation. CASE: A 71-year-old male patient presented
      with a venous leg ulcer (VLU), having incurred a crushing injury and fracture
      requiring surgical repair 16 years earlier. The patient's history was significant
      for obesity, smoking 1 cigar daily, hypertension, and lower extremity venous
      insufficiency; medications included amlodipine and lisinopril. The wound
      initially responded well to advanced wound products and compression, but wound
      healing subsequently stalled. A collagen-containing alginate dressing was added
      to the treatment regimen and the wound closed within 2 weeks. CONCLUSION: We
      postulate that lisinopril may have contributed to the observed delayed healing
      and targeted this potential impediment to wound healing with a readily available
      topical collagen-containing product resulting in a rapid wound closure after a
      significant delay in progress toward wound healing.

PMID- 25377116
TI  - Solvation effects on chemical shifts by embedded cluster integral equation
      theory.
AB  - The accurate computational prediction of nuclear magnetic resonance (NMR)
      parameters like chemical shifts represents a challenge if the species studied is
      immersed in strongly polarizing environments such as water. Common approaches to
      treating a solvent in the form of, e.g., the polarizable continuum model (PCM)
      ignore strong directional interactions such as H-bonds to the solvent which can
      have substantial impact on magnetic shieldings. We here present a computational
      methodology that accounts for atomic-level solvent effects on NMR parameters by
      extending the embedded cluster reference interaction site model (EC-RISM)
      integral equation theory to the prediction of chemical shifts of N
      methylacetamide (NMA) in aqueous solution. We examine the influence of various so
      called closure approximations of the underlying three-dimensional RISM theory as
      well as the impact of basis set size and different treatment of electrostatic
      solute-solvent interactions. We find considerable and systematic improvement over
      reference PCM and gas phase calculations. A smaller basis set in combination with
      a simple point charge model already yields good performance which can be further
      improved by employing exact electrostatic quantum-mechanical solute-solvent
      interaction energies. A larger basis set benefits more significantly from exact
      over point charge electrostatics, which can be related to differences of the
      solvent's charge distribution. 

PMID- 25377117
TI  - Effect of mineralocorticoids on acid-base balance.
AB  - Aldosterone is classically associated with the regulation of salt and potassium
      homeostasis but has also profound effects on acid-base balance. During acidosis,
      circulating aldosterone levels are increased and the hormone acts in concert with
      angiotensin II and other factors to stimulate renal acid excretion.
      Pharmacological blockade of aldosterone action as well as inherited or acquired
      syndromes of impaired aldosterone release or action impair the renal response to
      acid loading and cause hyperkalemic renal tubular acidosis. The mineralocorticoid
      receptor (MR) mediating the genomic effects of aldosterone is expressed in all
      cells of the distal nephron including all subtypes of intercalated cells. In acid
      secretory type A intercalated cells, aldosterone stimulates proton secretion into
      urine, whereas in non-type A intercalated cells, aldosterone increases the
      activity of the luminal anion exchanger pendrin stimulating bicarbonate secretion
      and chloride reabsorption. Aldosterone has also stimulatory effects on proton
      secretion that may be mediated by a non-genomic pathway. In addition, aldosterone
      indirectly stimulates renal acid excretion by enhancing sodium reabsorption
      through the epithelial sodium channel ENaC. Increased sodium reabsorption
      enhances the lumen-negative transepithelial voltage that facilitates proton
      secretion by neighboring intercalated cells. This indirect coupling of sodium
      reabsorption and proton secretion is thought to underlie the fludrocortisone
      furosemide test for maximal urinary acidification in patients with suspected
      distal renal tubular acidosis. In patients with CKD, acidosis-induced aldosterone
      may contribute to progression of kidney disease. In summary, aldosterone is a
      powerful regulator of renal acid excretion required for normal acid-base balance.

PMID- 25377118
TI  - Antioxidant and tyrosinase inhibitory effects of neolignan glycosides from
      Crataegus pinnatifida seeds.
AB  - In our efforts to find an inhibitor of melanin formation and develop potential
      depigmenting agents for skin-protecting cosmetics and medicinal products from
      natural resources, we focused on the seeds of Crataegus pinnatifida which showed
      antioxidant and tyrosinase-inhibiting activities. By activity-guided
      fractionation of an extract of C. pinnatifida seeds, four new neolignan
      glycosides, pinnatifidaninsides A-D (1-4), along with two known compounds (5-6),
      were isolated. Their structures were elucidated by spectroscopic analyses,
      especially 1D, 2D NMR and CD spectra. The antioxidant and tyrosinase-inhibiting
      activities of all isolates were assayed. Compound 6 showed good activity against
      2,2-diphenyl-1-pikrylhydrazyl, while compounds 1, 2, 5, and 6 exhibited strong
      2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) free radical scavenging
      activity, being as effective as, or even more effective than the positive control
      Trolox. Moreover, compounds 5 and 6 displayed a moderate mushroom tyrosinase
      inhibitory activity. 

PMID- 25377120
TI  - Peptidyl-prolyl isomerases: functionality and potential therapeutic targets in
      cardiovascular disease.
AB  - Peptidyl-prolyl cis/trans isomerases (PPIases) are a conserved group of enzymes
      that catalyse the conversion between cis and trans conformations of proline
      imidic peptide bonds. These enzymes play critical roles in regulatory mechanisms
      of cellular function and pathophysiology of disease. There are three different
      classes of PPIases and increasing interest in the development of specific PPIase
      inhibitors. Cyclosporine A, FK506, rapamycin and juglone are known PPIase
      inhibitors. Herein, we review recent advances in elucidating the role and
      regulation of the PPIase family in vascular disease. We focus on peptidyl-prolyl
      cis/trans isomerase NIMA-interacting 1 (Pin1), an important member of the PPIase
      family that plays a role in cell cycle progression, gene expression, cell
      signalling and cell proliferation. In addition, Pin1 may be involved in
      atherosclerosis. The unique role of Pin1 as a molecular switch that impacts on
      multiple downstream pathways necessitates the evaluation of a highly specific
      Pin1 inhibitor to aid in potential therapeutic drug discovery. 

PMID- 25377121
TI  - Is the use of formulae a reliable way to predict the accuracy of genomic
      selection?
AB  - We studied four formulae used to predict the accuracy of genomic selection prior
      to genotyping. The objectives of our study were to investigate the impact of the
      parameters of each formula on the values of accuracy calculated using these
      formulae, and to check whether the accuracies reported in the literature are in
      agreement with the formulae. First, we computed the marginal distribution of
      accuracy (by integration) for each parameter of all four formulae: heritability
      h(2) , reference population size T, number of markers M and number of effective
      segments in the genome Me . Then, we collected 145 accuracies and corresponding
      parameters reported in 13 publications on genomic selection (mainly in dairy
      cattle), and performed analysis of variance to test the differences between
      observed and predicted accuracy with effects of formulae and parameters. The
      variation of accuracy for different values of each parameter indicated that two
      parameters, T and Me, had a significant impact and that considerable differences
      existed between the formulae (mean accuracies differed by up to 0.20 point). The
      results of our meta-analysis showed a big formula effect on the accuracies
      predicted using each formula, and also a significant effect of the value obtained
      for Me calculated from Ne (effective population size). Each formula can therefore
      be demonstrated to be optimal depending on the assumption used for Me . In
      conclusion, no rules can be applied to predict the reliability of genomic
      selection using these formulae. 

PMID- 25377122
TI  - Promoter polymorphisms in genes involved in porcine myogenesis influence their
      transcriptional activity.
AB  - BACKGROUND: Success of meat production and selection for improvement of meat
      quality is among the primary aims in animal production. Meat quality traits are
      economically important in swine; however, the underlying genetic nature is very
      complex. Therefore, an improved pork production strongly depends on identifying
      and studying how genetic variations contribute to modulate gene expression.
      Promoters are key regions in gene modulation as they harbour several binding
      motifs to transcription regulatory factors. Therefore, polymorphisms in these
      regions are likely to deeply affect RNA levels and consequently protein
      synthesis. In this study, we report the identification of single nucleotide
      polymorphisms (SNPs) in promoter regions of candidate genes involved in
      development, cellular differentiation and muscle growth in Sus scrofa. We
      identified SNPs in the promoter regions of genes belonging to the Myogenic
      Regulatory Factors (MRF) gene family (the Myogenic Differentiation gene, MYOD1)
      and to Growth and Differentiation Factors (GDF) gene family (Myostatin gene,
      MSTN, GDF8), in Casertana and Large White breeds. The purpose of this study was
      to investigate if polymorphisms in the promoters could affect the transcriptional
      activity of these genes. With this aim, we evaluated in vitro the functional
      activity of the luciferase reporter gene luc2 activity, driven by two constructs
      carrying different promoter haplotypes. RESULTS: We tested the effects of the
      G302A (U12574) transition on the promoter efficiency in MYOD1 gene. We
      ascertained a difference in transcription efficiency for the two variants. A
      stronger activity of the A-carrying construct is more evident in C2C12. The
      luciferase expression driven by the MYOD1-A allelic variant displayed a 3.8-fold
      increased transcriptional activity. We investigated the activity of two haplotype
      variants (AY527152) in the promoter of GDF8 gene. The haploptype-1 (A435-A447
      A879) up-regulated the expression of the reporter gene by a two-fold increase,
      and hence presumably of the GDF8 gene, in both CHO and C2C12 cultured cells.
      CONCLUSIONS: In vitro the MYOD1-A allelic variant could up-regulate the
      expression of MYOD1 gene. Additionally, we could assess a different response of
      in vitro gene expression according to cell type used to transfect constructs,
      suggesting that MyoD activation is regulated by mechanisms that are specific of
      myoblasts.

PMID- 25377123
TI  - Antioxidant status and the risk of elevated C-reactive protein 12 years later.
AB  - BACKGROUND/AIMS: Low-grade inflammation is an independent risk factor for
      cardiovascular disease. Relationships between the antioxidant status and
      inflammatory biomarkers could give new insights into cardiovascular disease
      prevention. We investigated long-term associations between the antioxidant
      nutrient (vitamin C, alpha-tocopherol, beta-carotene) status and C-reactive
      protein (CRP) in a population-based cohort. METHODS: Subjects included in the
      French SU.VI.MAX trial study who had available data on baseline (1994-1995) blood
      nutrient concentrations and CRP measurements 12 years later (2007-2009) were
      included. Associations between baseline antioxidant circulating concentrations
      and elevated CRP (>3 mg/l) were investigated in multivariate logistic regression
      models. Subgroup analyses were performed according to gender, supplementation
      group of the initial trial, smoking status, and alcohol intake. RESULTS: Serum
      alpha-tocopherol (n = 2,060) and vitamin C (n = 1,719) concentrations [odds ratio
      (OR) and 95% confidence interval (95% CI) quintile 5 vs. 1: OR 1.10 (95% CI 0.71
      1.73), p for trend = 0.533, vs. OR 0.79 (95% CI 0.48-1.29), p for trend = 0.121,
      respectively] were not associated with elevated CRP concentrations. The beta
      carotene status (n = 2,048) was inversely associated with elevated CRP [adjusted
      OR quintile 5 vs. 1: OR 0.61 (95% CI 0.38-0.98), p for trend = 0.01]. Subgroup
      analyses showed that associations were stronger in women (p for trend = 0.004),
      never smokers (p for trend = 0.009) and subjects in the supplementation group (p
      for trend = 0.002). CONCLUSIONS: Our results suggest that the beta-carotene
      status may be inversely associated with low-grade inflammation in the long term.

PMID- 25377124
TI  - Value of serum cystatin C in estimating renal function in children with non-renal
      solid organ transplantation.
AB  - Children with non-renal solid organ transplants are surviving longer, but outcome
      is complicated by CKD. Accurate and frequent renal function monitoring is
      imperative to recognize and institute measures early to reverse, prevent, or
      arrest progression. This study of 59 children determined the accuracy (P30),
      bias, sensitivity and specificity between measured renal function by NM-GFR, and
      estimated GFR by three formulas: Filler (serum cystatin C), mSchwartz (serum
      creatinine), and CKiD (serum cystatin C, creatinine, urea, and height). Mean GFR
      by all formulas differed significantly from NM-GFR. Filler and mSchwartz formulas
      significantly increased the proportion of patients with GFR >= 90 mL/min/1.73
      m(2) (CKD stage 1) while decreasing those with GFR 60-89 mL/min/1.73 m(2) (CKD
      stage 2). All formulas overestimated GFR. CKiD showed the highest P30 and lowest
      bias (79.7%; 6.9 mL/min/1.73 m(2) ) followed by Filler (67.7%; 19.9 mL/min/1.73
      m(2) ) and Schwartz (57.6%; 26.8 mL/min/1.73 m(2) ) for all GFR values. All
      formulas performed best with GFR >= 90 mL/min/1.73 m(2) , but CKiD was the only
      formula to achieve 91.1% accuracy. All formulas showed high sensitivities, but
      low specificities at NM-GFR cutoff at 90. Thus, GFR estimated by CKiD followed by
      Filler formula is an adequate method to monitor renal function closely and
      frequently in these children. 

PMID- 25377125
TI  - Single-cell transcriptomics: an emerging tool in the study of cardiometabolic
      disease.

PMID- 25377126
TI  - Current practice of cord clamping in the Netherlands: a questionnaire study.
AB  - BACKGROUND: Recent meta-analyses recommend delayed cord clamping (DCC) after
      uncomplicated births as well as preterm births, but there is no clear definition
      of timing and uniform national guidelines are lacking. OBJECTIVE: We aimed to
      investigate if guidelines for the timing of cord clamping (CC) are followed and
      what the national practice entails. METHODS: A postal questionnaire concerning CC
      after uncomplicated vaginal, Caesarean term and preterm deliveries was sent to
      all midwifery practices (n = 526) and obstetrical departments (n = 94) in the
      Netherlands. RESULTS: The response rate was 81% (500/620). CC protocols were
      present in 16 and 38% of midwifery and obstetric practices, respectively. Early
      cord clamping (ECC) was recommended in 54%, DCC in 33%, 6% indicated a specific
      time point and 7% did not specify. In current practice, DCC was applied after
      uncomplicated vaginal term deliveries in 90% and ECC in 6%, and no timing was
      specified in 4%. Midwives used DCC more often than obstetricians (97 vs. 75%).
      Cessation of cord pulsations was often (54%) used as a time point, 40% used a
      fixed time point, 2% waited for placental expulsion and 4% did not specify. ECC
      was preferred in obstetric practices after Caesarean deliveries (in 81%). In
      preterm births, ECC was practised by 36%, DCC by 54 and 10% did not specify.
      CONCLUSION: In the Netherlands, although often not protocolized, DCC is widely
      used after uncomplicated vaginal term and preterm deliveries, but not after
      Caesareans. Cessation of cord pulsation is often used as the time point for CC.

PMID- 25377127
TI  - Structurally engineered stackable and scalable 3D titanium-oxide switching
      devices for high-density nanoscale memory.
AB  - A 3D high-density switching device is realized utilizing titanium oxide, which is
      the most optimum material, but which is not practically demonstrated yet. The
      1S1R (one ReRAM with the developed switching device) exhibits memory
      characteristics with a significantly suppressed sneak current, which can be used
      to realize high-density ReRAM applications. 

PMID- 25377128
TI  - Unique molecular signatures of Alzheimer's disease amyloid beta peptide mutations
      and deletion during aggregate/oligomer/fibril formation.
AB  - The formation of amyloid beta (Abeta) peptide aggregates, oligomers, and fibrils
      is a dynamic process; however, the kinetics of their formation is not well
      understood. This study compares the time course of aggregate/fibril formation by
      transmission electron microscopy (TEM) analyses with that of oligomer/fibril
      formation by Western blot analysis under native and denaturing conditions.
      Efforts to deaggregate/defibrillate these peptides by using
      hexafluoroisopropanol, ammonium hydroxide, or dimethylsulfoxide did not change
      the nondenaturing polyacrylamide gel electrophoresis (PAGE) footprints or drive
      the peptides to a monomeric species. Regardless of the pretreatment protocol, TEM
      analyses reveal that all Abeta peptides (Abeta40, Abeta42, Abeta39E22Delta
      [Osaka], Abeta40E22G [Arctic], Abeta40E22Q [Dutch], and Abeta40A2T [Icelandic])
      immediately formed nonfibrillar, amorphous aggregates when first placed into
      solution with the Osaka mutation, quickly forming early-stage fibrils. The extent
      of fibril formation for other Abeta peptides is time dependent, with the Arctic
      mutation forming fibrils at 1 hr, the Dutch and Icelandic at 4 hr, Abeta42 at 8
      hr, and Abeta40 at 24 hr. In contrast, nondenaturing PAGE revealed unique
      footprints for the different Abeta species. The rapidity of aggregate formation
      and the rapid transition to fibrils, particularly for the Osaka deletion, suggest
      an important role for aggregates/fibrils of Abeta in the development of neuronal
      degeneration.

PMID- 25377129
TI  - Association between latent toxoplasmosis and cognition in adults: a cross
      sectional study.
AB  - Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and
      has been associated with cognitive deficits in some but not all animal models and
      in humans. We tested the hypothesis that latent toxoplasmosis is associated with
      decreased cognitive function in a large cross-sectional dataset, the National
      Health and Nutrition Examination Survey (NHANES). There were 4178 participants
      aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two
      ordinary least squares (OLS) regression models adjusted for the NHANES complex
      sampling design and weighted to represent the US population were estimated for
      simple reaction time, processing speed and short-term memory or attention. The
      first model included only main effects of latent toxoplasmosis and demographic
      control variables, and the second added interaction terms between latent
      toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and
      race-ethnicity. We also used multivariate models to assess all three cognitive
      outcomes in the same model. Although the models evaluating main effects only
      demonstrated no association between latent toxoplasmosis and the cognitive
      outcomes, significant interactions between latent toxoplasmosis and the PIR,
      between latent toxoplasmosis and educational attainment, and between latent
      toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may
      adversely affect cognitive function in certain groups.

PMID- 25377130
TI  - Bond competition and phase evolution on the IrTe2 surface.
AB  - Compounds with incommensurate structural modulations have been extensively
      studied in last several decades. However, the relationship between structurally
      incommensurate/commensurate phases and associated electronic states remains
      enigmatic. Here we report the coexisting of complex incommensurate structures and
      highly unusual electronic roughness on the surface of in situ cleaved IrTe2 by
      using scanning tunnelling microscopy/spectroscopy, corroborated with extensive
      density-functional theory calculations. This behaviour is traced to structural
      instability, which induces a structural transition from a trigonal to a triclinic
      lattice below transition temperature, giving rise to the formation of
      unidirectional structural modulations with distinct wavelengths, accompanied by
      the opening of a 'pseudo'-gap in the surface layer. With further cooling the
      surface adopts a structure that reflects an ~6 * periodicity that is different
      from the bulk 5 * periodicity. Calculations show that the structure distortion is
      not associated with a charge density wave, but is rather associated with Te p
      electron bonding.

PMID- 25377131
TI  - Disproportionate pupillary involvement in diabetic autonomic neuropathy.
AB  - OBJECTIVE: To study the degree of pupillary impairment in diabetic and non
      diabetic autonomic neuropathy. METHODS: We retrospectively sampled from all
      patients who underwent comprehensive autonomic testing and infrared pupillometry
      at UT Southwestern Medical Center. Composite autonomic severity score (CASS) and
      pupillary indices from the average of at least three pupillary response curves
      were recorded. We randomly matched patients with diabetic autonomic neuropathy
      (DAN) and patients with autonomic impairment unrelated to diabetes (non-DAN)
      based on gender, age (+/-5 years), and CASS (+/-1 point). We used the paired t
      test to analyze differences between the groups. RESULTS: We identified 40
      patients with DAN and 40 matched controls with non-DAN. M:F ratio was 1:1. Mean
      CASS was 4.2 and mean age was 62.4 years. Six had type I and the rest had type II
      diabetes mellitus. Both absolute constriction amplitude (ACA) and maximum
      constriction velocity (MCV) were significantly lower in DAN compared to non-DAN;
      mean ACA was 0.9 mm vs. 1.17 mm (p = 0.0077) and mean MCV was 2.8 vs. 3.6 mm/s (p
      = 0.0039). Severely diminished MCV for age was noted in 48 % of diabetic and in
      only 28 % of non-DAN patients. The ACA-corrected time to 75 % re-dilation was
      significantly delayed in DAN vs. non-DAN [mean 3.2 vs. 1.7 s/mm (p = 0.025)]. A
      statistically significant decline was noted for both the MCV and ACA with higher
      cardiovagal subscores among DAN patients. CONCLUSIONS: Parasympathetic and
      sympathetic pupillary dysfunction appears to be a common feature of autonomic
      impairment in diabetes compared to non-diabetic causes of autonomic impairment.

PMID- 25377132
TI  - Phylogeny and Reclassification of Hemistasia phaeocysticola (Scherffel)
      Elbrachter & Schnepf, 1996.
AB  - Hemistasia phaeocysticola is a marine flagellate that preys on diatoms and
      dinoflagellates among others. Although its morphology and ultrastructure were
      previously observed and characterized, its phylogenetic position has not been
      analyzed using molecular sequence data. This flagellate was classified as a
      kinetoplastid on the basis of the presence of a kinetoplast in the mitochondrion.
      However, several morphological characteristics similar to those of diplonemids, a
      sister group of kinetoplastids, have also been noted. Herein, we report that H.
      phaeocysticola branches within the diplonemid clade in the phylogenetic tree
      reconstructed by analyzing 18S rRNA gene sequences. Its systematic placement
      based on this finding is also discussed.

PMID- 25377133
TI  - The diagnostic accuracy of screening questionnaires for the identification of
      adults with epilepsy: a systematic review.
AB  - OBJECTIVE: To describe the diagnostic accuracy of screening questionnaires to
      identify epilepsy in adults, we performed a systematic review of diagnostic
      studies that assessed the sensitivity and specificity of such screening
      questionnaires as compared to a physician's clinical assessment. METHODS: We
      searched Ovid MEDLINE (1946 to present) and Ovid EMBASE (1947 to present) for
      studies that estimated the sensitivity and specificity of nonphysician
      administered screening questionnaires for adults with epilepsy. Both telephone
      and in-person administered questionnaires were included, whether applied to
      population or hospital/clinic-based cohorts. The risk of bias was assessed using
      the Quality Assessment of Diagnostic Studies-2 (QUADAS-2) tool. RESULTS: Our
      initial search strategy resulted in 917 records. We found nine studies eligible
      for inclusion. The estimated sensitivity and specificity of the questionnaires
      used to identify persons with a lifetime history of epilepsy ranged from 81.5% to
      100% and 65.6% to 99.2%, respectively. The sensitivity and specificity of these
      questionnaires in identifying persons with active epilepsy ranged from 48.6% to
      100% and 73.9% to 99.9%, respectively. Overall we found a high risk of bias in
      patient selection and study flow in the majority of studies. SIGNIFICANCE: We
      identified nine validation studies of epilepsy screening questionnaires,
      summarized their study characteristics, presented their results, and performed a
      rigorous quality assessment. This review serves as a basis for future studies by
      providing a systematic review of existing work. Future research addressing
      previous limitations will ultimately allow us to more accurately estimate the
      burden and risk of epilepsy in the general population.

PMID- 25377134
TI  - Does the nature of chondrolabral injury affect the results of open surgery for
      femoroacetabular impingement?
AB  - BACKGROUND: The degree to which patient characteristics, clinical outcomes, and
      the nature, severity, and corresponding treatment of chondrolabral injury in
      femoroacetabular impingement (FAI) is associated with failure after surgery is
      incompletely understood. QUESTIONS/PURPOSES: (1) Are patient factors associated
      with failure (age, sex, body mass index, and preoperative modified Harris hip
      score [mHHS]) in the open surgical treatment of FAI? (2) Is the nature of
      chondrolabral injury associated with failure? (3) Are any specific chondrolabral
      injury treatment methods superior? METHODS: Between 2000 and 2008, 172 open
      surgical procedures in 167 patients were performed for the treatment of FAI by
      two surgeons at two separate academic medical centers. Ultimately, 142 patients
      were included in this retrospective study. Mean followup was 3 years (range, 1-12
      years). Patient and clinical factors along with the nature, severity, and
      treatment of chondrolabral injuries were assessed for an association with
      failure, defined as conversion to THA or the inability to achieve the minimum
      clinically important difference of the mHHS. Thirty-two percent (45 of 142) of
      patients failed open surgical treatment of FAI. RESULTS: Patient factors
      associated with failure included age (odds ratio [OR], 1.04; p = 0.036) and
      preoperative mHHS (OR, 4.42; p = 0.033). Neither the nature of the labral lesion
      nor the severity of the chondral lesion demonstrated a relationship with failure
      (p > 0.05). Surgically, labral refixation was associated with a decrease in the
      risk of failure (OR, 0.31; p = 0.039). CONCLUSIONS: We were unable to identify an
      increased risk of poor outcomes based on sex, body mass index, or severity of
      chondrolabral lesions. We did find an increased risk of poorer outcomes
      associated with age. Labral refixation was associated with a decrease in the risk
      of failure indicating that treatment methodology, rather than the nature of the
      chondrolabral injury, may be associated with clinical failure. Future studies
      will be needed to help determine optimal treatment strategies for chondrolabral
      injuries.

PMID- 25377135
TI  - CORR Insights(r): Injury risk to extraosseous knee vasculature during
      osteotomies: a cadaveric study with ct and dissection analysis.

PMID- 25377136
TI  - CORR Insights (r): Good functional recovery of complex elbow dislocations treated
      with hinged external fixation: a multicenter prospective study.

PMID- 25377137
TI  - Determination of human albumin in serum and urine samples by constant-energy
      synchronous fluorescence method.
AB  - A sensitive spectrofluorimetric method using constant-energy synchronous
      fluorescence technique is proposed for the determination of human albumin without
      separation. In this method, no reagent was used for enhancement of the
      fluorescence signal of albumin in the solution. Effects of some parameters, such
      as energy difference between excitation and emission monochromators (DeltaE),
      emission and excitation slit widths and scan rate of wavelength were studied and
      the optimum conditions were established. For this purpose factorial design and
      response surface method were employed for optimization of the effective
      parameters on the fluorescence signal. The results showed that the scan rate of
      the wavelength has no significant effect on the analytical signal. The
      calibration curve was linear in the range 0.1-220.0 ug mL(-1) of albumin with a
      detection limit of 7.0 * 10(-3)  ug mL(-1). The relative standard deviations
      (RSD) for six replicate measurements of albumin were calculated as 2.2%, 1.7% and
      1.3% for 0.5, 10.0 and 100.0 ug mL(-1) albumin, respectively. Furthermore the
      proposed method has been employed for the determination of albumin in human serum
      and urine samples.

PMID- 25377138
TI  - Human Fungal Pathogens of Mucorales and Entomophthorales.
AB  - In recent years, we have seen an increase in the number of immunocompromised
      cohorts as a result of infections and/or medical conditions, which has resulted
      in an increased incidence of fungal infections. Although rare, the incidence of
      infections caused by fungi belonging to basal fungal lineages is also
      continuously increasing. Basal fungal lineages diverged at an early point during
      the evolution of the fungal lineage, in which, in a simplified four-phylum fungal
      kingdom, Zygomycota and Chytridiomycota belong to the basal fungi, distinguishing
      them from Ascomycota and Basidiomycota. Currently there are no known human
      infections caused by fungi in Chytridiomycota; only Zygomycotan fungi are known
      to infect humans. Hence, infections caused by zygomycetes have been called
      zygomycosis, and the term "zygomycosis" is often used as a synonym for
      "mucormycosis." In the four-phylum fungal kingdom system, Zygomycota is
      classified mainly based on morphology, including the ability to form coenocytic
      (aseptated) hyphae and zygospores (sexual spores). In the Zygomycota, there are
      10 known orders, two of which, the Mucorales and Entomophthorales, contain
      species that can infect humans, and the infection has historically been known as
      zygomycosis. However, recent multilocus sequence typing analyses (the fungal tree
      of life [AFTOL] project) revealed that the Zygomycota forms not a monophyletic
      clade but instead a polyphyletic clade, whereas Ascomycota and Basidiomycota are
      monophyletic. Thus, the term "zygomycosis" needed to be further specified,
      resulting in the terms "mucormycosis" and "entomophthoramycosis." This review
      covers these two different types of fungal infections.

PMID- 25377139
TI  - Treatment principles for the management of mold infections.
AB  - Survival rates among immunocompromised patients with invasive mold infections
      have markedly improved over the last decade with earlier diagnosis and new
      antifungal treatment options. Yet, increasing antifungal resistance, breakthrough
      infections with intrinsically resistant fungi, and potentially life-threatening
      adverse effects and drug interactions are becoming more problematic, especially
      with prolonged therapy. Evidence-based recommendations for treating invasive
      aspergillosis and mucormycosis provide excellent guidance on the initial workup
      and treatment of these molds, but they cannot address all of the key management
      issues. Herein, we discuss 10 general treatment principles in the management of
      invasive mold disease in immunocompromised patients and discuss how these
      principles can be integrated to develop an effective, individualized treatment
      plan.

PMID- 25377141
TI  - Highly penetrant alleles in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a complex disease caused by a
      combination of genetic and environmental factors. Genome-wide association studies
      have identified several common genetic variants associated with AMD, which
      together account for 15%-65% of the heritability of AMD. Multiple hypotheses to
      clarify the unexplained portion of genetic variance have been proposed, such as
      gene-gene interactions, gene-environment interactions, structural variations,
      epigenetics, and rare variants. Several studies support a role for rare variants
      with large effect sizes in the pathogenesis of AMD. In this work, we review the
      methods that can be used to detect rare variants in common diseases, as well as
      the recent progress that has been made in the identification of rare variants in
      AMD. In addition, the relevance of these rare variants for diagnosis, prognosis,
      and treatment of AMD is highlighted. 

PMID- 25377140
TI  - Adaptive immunity to fungi.
AB  - Life-threatening fungal infections have risen sharply in recent years, owing to
      the advances and intensity of medical care that may blunt immunity in patients.
      This emerging crisis has created the growing need to clarify immune defense
      mechanisms against fungi with the ultimate goal of therapeutic intervention. We
      describe recent insights in understanding the mammalian immune defenses that are
      deployed against pathogenic fungi. We focus on adaptive immunity to the major
      medically important fungi and emphasize three elements that coordinate the
      response: (1) dendritic cells and subsets that are mobilized against fungi in
      various anatomical compartments; (2) fungal molecular patterns and their
      corresponding receptors that signal responses and shape the differentiation of T
      cell subsets and B cells; and, ultimately (3) the effector and regulatory
      mechanisms that eliminate these invaders while constraining collateral damage to
      vital tissue. These insights create a foundation for the development of new,
      immune-based strategies for prevention or enhanced clearance of systemic fungal
      diseases. 

PMID- 25377143
TI  - Functional profiling of human fungal pathogen genomes.
AB  - Fungal infections are challenging to diagnose and often difficult to treat, with
      only a handful of drug classes existing. Understanding the molecular mechanisms
      by which pathogenic fungi cause human disease is imperative. Here, we discuss how
      the development and use of genome-scale genetic resources, such as whole-genome
      knockout collections, can address this unmet need. Using work in Saccharomcyes
      cerevisiae as a guide, studies of Cryptococcus neoformans and Candida albicans
      have shown how the challenges of large-scale gene deletion can be overcome, and
      how such collections can be effectively used to obtain insights into mechanisms
      of pathogenesis. We conclude that, with concerted efforts, full genome-wide
      functional analysis of human fungal pathogen genomes is within reach. 

PMID- 25377142
TI  - Immunity and Immunopathology in the Tuberculous Granuloma.
AB  - Granulomas, organized aggregates of immune cells, are a defining feature of
      tuberculosis (TB). Granuloma formation is implicated in the pathogenesis of a
      variety of inflammatory disorders. However, the tuberculous granuloma has been
      assigned the role of a host protective structure which "walls-off" mycobacteria.
      Work conducted over the past decade has provided a more nuanced view of its role
      in pathogenesis. On the one hand, pathogenic mycobacteria accelerate and exploit
      granuloma formation for their expansion and dissemination by manipulating host
      immune responses to turn leukocyte recruitment and cell death pathways in their
      favor. On the other hand, granuloma macrophages can preserve granuloma integrity
      by exerting a microbicidal immune response, thus preventing an even more rampant
      expansion of infection in the extracellular milieu. Even this host-beneficial
      immune response required to maintain the bacteria intracellular must be tempered,
      as an overly vigorous immune response can also cause granuloma breakdown, thereby
      directly supporting bacterial growth extracellularly. This review will discuss
      how mycobacteria manipulate inflammatory responses to drive granuloma formation
      and will consider the roles of the granuloma in pathogenesis and protective
      immunity, drawing from clinical studies of TB in humans and from animal models-
      rodents, zebrafish, and nonhuman primates. A deeper understanding of TB
      pathogenesis and immunity in the granuloma could suggest therapeutic approaches
      to abrogate the host-detrimental aspects of granuloma formation to convert it
      into the host-beneficial structure that it has been thought to be for nearly a
      century.

PMID- 25377145
TI  - Research exemption/experimental use in the European Union: patents do not block
      the progress of science.
AB  - In the public debate about patents, specifically in the area of biotechnology,
      the position has been taken that patents block the progress of science. As we
      demonstrate in this review, this is not the case in the European Union (EU). The
      national patent acts of the EU member states define research and experimental use
      exemptions from patent infringement that allow sufficient room for research
      activities to promote innovation. This review provides a comparative overview of
      the legal requirements and the extent and limitations of experimental use
      exemptions, including the so-called Bolar provision, in Germany, the United
      Kingdom, France, Spain, Italy, and The Netherlands. The legal framework in the
      respective countries is illustrated with reference to practical examples
      concerning tests on patent-protected genetic targets and antibodies. Specific
      questions concerning the use of patent-protected research tools, the outsourcing
      of research activities, and the use of preparatory and supplying acts for
      experimental purposes that are necessary for conducting experiments are covered. 

PMID- 25377146
TI  - Ethical challenges in cross-cultural research: a student researcher's
      perspective.

PMID- 25377144
TI  - Aspergillus fumigatus and related species.
AB  - The genus Aspergillus contains etiologic agents of aspergillosis. The clinical
      manifestations of the disease range from allergic reaction to invasive pulmonary
      infection. Among the pathogenic aspergilli, Aspergillus fumigatus is most
      ubiquitous in the environment and is the major cause of the disease, followed by
      Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus nidulans,
      and several species in the section Fumigati that morphologically resemble A.
      fumigatus. Patients that are at risk for acquiring aspergillosis are those with
      an altered immune system. Early diagnosis, species identification, and adequate
      antifungal therapy are key elements for treatment of the disease, especially in
      cases of pulmonary invasive aspergillosis that often advance very rapidly.
      Incorporating knowledge of the basic biology of Aspergillus species to that of
      the diseases that they cause is fundamental for further progress in the field. 

PMID- 25377147
TI  - How should we interpret the new Dutch evidence on home birth?

PMID- 25377148
TI  - Spontaneous sternal collapse in multiple myeloma.

PMID- 25377149
TI  - Demographic correlates of anxiety and depression symptoms in chronic sinonasal
      diseases.
AB  - OBJECTIVES: To explore mental health of patients with olfactory loss due to
      chronic sinonasal diseases and investigate the effects of age-, gender-, and
      socio-economic variables on anxiety and depression symptoms. METHODOLOGY: One
      hundred and eight patients (62 males; mean age: 39.78 +/- 16.11 years), suffering
      from olfactory impairment due to chronic rhinosinusitis and allergic rhinitis and
      30 healthy subjects (16 males; mean age, 37.03 +/- 13.09 years) were studied.
      Olfactory function was evaluated using "Sniffin' Sticks" test. All patients
      completed four validated questionnaires specific for assessing anxiety and
      depression (Zung Anxiety Scale, State-Trait Anxiety Inventory-STAI, Zung
      Depression Scale, and Beck Depression Inventory-BDI). RESULTS: We found
      significantly more severe anxiety and depression symptoms in anosmic (all p <
      0.001) and hyposmic patients compared to healthy controls. No significant
      differences were observed between normosmic patients and controls. Scores in all
      psychological measures were significantly higher in elderly and female patients
      as well as in low, compared to high, socio-economic status patients. No
      significant differences were found between low and medium socio-economic level.
      CONCLUSIONS: Olfactory loss in chronic sinonasal diseases was found to be
      associated with anxiety and depression symptoms. Moreover, anxiety was correlated
      with depression. With regard to patients' demographics, female gender and low
      socioeconomic status proved to be independently correlated with anxiety and
      depression levels.

PMID- 25377150
TI  - Severe anorexia nervosa in a 20-year-old male with pericardial effusion and
      cortical atrophy.
AB  - This case report describes a 20-year-old man with a severe presentation of
      anorexia nervosa. His case is unique in that he presented at 49% of his ideal
      body weight and had a body mass index (BMI) of 11.59. In addition, he had
      cognitive slowing on exam and had cortical atrophy on a head CT. Other medical
      complications included pericardial tamponade that was treated with an open window
      pericardiocentesis, hepatitis, and anemia. He was treated nutritionally, first
      with a Dobb-Hoff tube and then with oral feedings, as well as had group,
      individual, and family therapies. He responded well to treatment, his labs
      normalized and he was discharged at 75% of his ideal body weight after a weight
      increase of 40 pounds and after 106 days of hospitalization at our facility. In
      addition, a head CT was repeated and the cortical atrophy had resolved. 

PMID- 25377151
TI  - Paliperidone for the treatment of ketamine-induced psychosis: a case report.
AB  - Ketamine is an anaesthetic and analgesic drug synthesized in the 1960s from
      phencyclidine. The recreational use of ketamine increased among the dance culture
      of techno and house music, in particular in clubs, discotheques, and rave
      parties. The psychotropic effects of ketamine are now well known and they range
      from dissociation to positive, negative, and cognitive schizophrenia-like
      symptoms. We report a case of a chronic oral consumption of ketamine which
      induced agitation, behavioral abnormalities, and loss of contact with reality in
      a poly-drug abuser; these symptoms persisted more than two weeks after the drug
      consumption had stopped. Antipsychotic treatment with paliperidone led to a
      successful management of the psychosis, getting a complete resolution of the
      clinical picture. Paliperidone has proven to be very effective in the treatment
      of ketamine-induced disorders. Moreover, the pharmacological action and
      metabolism of paliperidone are poorly dependent from the activity of liver
      enzymes, so that it seems to be one of the best second generation antipsychotics
      for the treatment of smokers and alcohol abusers. 

PMID- 25377152
TI  - Plasma galanin is a biomarker for severity of major depressive disorder.
AB  - OBJECTIVE: This study investigated the association between plasma galanin level
      and depression severity. METHODS: The severity of depression symptoms of 79
      patients with major depressive disorder (MDD; 52 women and 27 men, 71 patients in
      onset, 8 in remission) was assessed using the 17-item Hamilton Depression Rating
      Scale. Venous fasting blood samples (5 mL) were taken from the 79 MDD patients,
      35 healthy siblings, and 19 healthy controls, and plasma samples were prepared.
      Galanin levels in the plasma were measured by radioimmunoassay. RESULTS: Plasma
      galanin in MDD patients was significantly higher than that of remission patients,
      healthy siblings, or healthy controls (P < 0.05) There was no significant
      difference between the healthy sibling and healthy control groups (P = 0.924).
      Plasma galanin of remission patients was also significantly higher than that of
      healthy controls (P < 0.05). There was no significant correlation between age and
      galanin levels in the 79 patients (r = 0.053, P = 0.646), nor was there a
      correlation between age and galanin levels when patients were stratified by
      gender (P > 0.05). There was a significant positive correlation between plasma
      galanin levels and depression severity in women MDD patients (r = 0.329, df = 42,
      P = 0.020), but not in men patients. CONCLUSIONS: Plasma galanin levels may be an
      important biomarker for depression severity, especially in female patients.

PMID- 25377154
TI  - Relationship of serious psychological distress to quality of life in adults with
      diabetes.
AB  - OBJECTIVE: To examine the association between serious psychological distress
      (SPD) and the Physical and Mental Health components of Quality of Life (QOL)
      while controlling for depression in a national sample of adults with diabetes.
      METHODS: SPD was assessed in 1,659 adults with diabetes who participated in the
      2007 Medical Care Expenditure Survey (MEPS). SPD was measured by the 6-item
      Kessler scale. Depression was assessed with the PHQ-2 screen. Quality of life was
      measured with the physical (PCS) and mental (MCS) components of the SF-12. We
      used multiple linear regression to assess the relationship between SPD and
      quality of life while controlling for relevant covariates and depression screen
      results to assess the independent effect of SPD on QOL above and beyond the
      effect of depression. RESULTS: Among US adults with diabetes, 9% had SPD and
      15.4% screened positive for depression. Among those with SPD, 85.8% had
      depression and among those with depression, 50.5% had SPD. In the adjusted model
      for socio-demographic factors and comorbidities, SPD was significantly associated
      with lower PCS scores (-5.51 95% CI -7.55; -3.45) and MCS scores (-18.99 95% CI 
      20.81; -17.18). In the adjusted model that also controlled for depression, SPD
      was still significantly associated with lower PCS scores (-3.03 95% CI -5.63; 
      0.43) and MCS scores (-9.46 95% CI -11.67; -7.24). CONCLUSIONS: Among U. S.
      adults, SPD is associated with significantly diminished QOL above and beyond the
      effects of depression. Targeted interventions to mitigate the adverse effects of
      SPD are needed, independent of programs to address depression.

PMID- 25377153
TI  - A mixed methods exploration of family involvement in medical care for older
      adults with serious mental illness.
AB  - OBJECTIVE: Many older persons with serious mental illness (SMI) suffer from high
      rates of comorbid medical conditions. Although families play a critical role in
      psychiatric illness management among adults with SMI, their contributions to
      improving health outcomes in this population has received little attention. This
      study explored family involvement in medical care for older adults with SMI.
      METHODS: This mixed methods study involved analysis of quantitative data
      collected from older adults with SMI and cardiovascular risk (n = 28)
      participating in a pilot study of an intervention designed to improve patient
      centered primary care augmented by qualitative interviews with their relatives (n
      = 13) to explore family involvement in medical care. RESULTS: Approximately 89%
      of older adults with SMI reported family involvement in at least one aspect of
      their medical care (e.g., medication reminders, medical decision making).
      However, many family members reported that they were rarely involved in their
      relative's medical visits, and most did not perceive a need to be involved during
      routine care. Family members identified obesity as their relative's primary
      health concern and many wanted guidance from providers on effective strategies
      for supporting weight loss. CONCLUSIONS: Although many family members did not
      perceive a need to be involved in their relative's routine medical visits, they
      expressed interest in talking with providers about how to help their relative
      change unhealthy behaviors. Educating patients, families, and providers about the
      potential benefits of family involvement in medical care, including routine
      medical visits for persons with SMI and cardiovascular health risk may promote
      patient- and family-centered collaboration in this high-risk population.

PMID- 25377155
TI  - Case report: transient left bundle branch block associated with ECT.
AB  - We present the first reported case of transient left bundle branch block (LBBB)
      occurring during electroconvulsive therapy (ECT). LBBB is an important clinical
      finding, as it is associated with a significant increase in mortality. Physicians
      providing ECT should be aware of the significance of new-onset LBBB; it may occur
      during treatment. 

PMID- 25377156
TI  - Obstructive sleep apnea in non-dialysis chronic kidney disease patients.
AB  - There is an enormous increase in the burden of chronic kidney disease both in
      developing and developed countries. There is a paucity of data on obstructive
      sleep apnea (OSA) in chronic kidney disease (CKD) patients in India. We used a
      cross-sectional prospective observational study to determine the prevalence of
      OSA in non-dialysis CKD patients. Of the 647 CKD patients 302 patients were in
      stage II, III and IV. The study population was screened using the Berlin
      questionnaire and 87 patients were positive for OSA (28%). Among the 87, 37
      patients were excluded based on the exclusion criteria. Fifty patients underwent
      a split night sleep study. Stage II, III CKD patients were clubbed as early CKD
      or group one and stage IV CKD patients were clubbed as late CKD or group two. The
      spilt night study revealed an 88% incidence of OSA of varying severity. A sub
      group analysis was done to assess the severity of OSA. A statistical significance
      (p<0.05) between early and late CKD group was observed with respect to AHI and
      ODI. An improvement in the late CKD is observed and the Z values for AHI and ODI
      are 4.273 and 2.307, respectively. The prevalence and incidence of OSA was found
      to be 28% and 88% in non-dialysis CKD patients, respectively and the risk and
      severity of OSA increased with the progression of CKD stages and thus
      necessitating the need for screening the non-dialysis CKD population.

PMID- 25377157
TI  - A phase I, open-label, multicenter study to evaluate the pharmacokinetics and
      safety of oral panobinostat in patients with advanced solid tumors and varying
      degrees of renal function.
AB  - PURPOSE: This study assessed the pharmacokinetics and safety of oral panobinostat
      and its metabolite BJB432 in patients with advanced solid tumors and normal to
      severely impaired renal function. METHODS: Patients with varying degrees of renal
      impairment, defined by their 24-h baseline urine creatinine clearance (as normal,
      mild, moderate or severe), received a single oral dose of 30 mg panobinostat.
      Serial plasma samples were collected pre-dose and up to 96-h post-dose. Serial
      urine samples were collected for 24-h post-dose. Following the serial PK
      sampling, patients received 30 mg oral panobinostat thrice weekly for as long as
      the patient had benefit. Pharmacokinetic parameters were derived using non
      compartmental analysis. RESULTS: Thirty-seven patients were enrolled, and median
      age was 64 (range 40-81) years. Eleven patients had normal renal function; 10,
      10, and 6 patients had mild, moderate, and severe renal impairment, respectively.
      Geometric means of AUC(0-infinity) in the normal, mild, moderate, and severe
      groups were 224.5, 144.3, 223.1, and 131.7 ng h/mL, respectively. Geometric mean
      ratio of BJB432 to parent drug plasma AUC(0-infinity) was 0.64 in the normal
      group and increased to 0.81, 1.13, and 1.20 in the mild, moderate, and severe
      groups, respectively. The fraction excreted as unchanged panobinostat was small
      (<2 %), with a large variability. The renal clearance of panobinostat and
      tolerability was similar across all four groups. CONCLUSION: Systemic exposure to
      panobinostat did not increase with severity of renal impairment, and the drug was
      tolerated equally; thus, patients with renal impairment do not require starting
      dose adjustments.

PMID- 25377158
TI  - Population pharmacokinetics of HM781-36 (poziotinib), pan-human EGF receptor
      (HER) inhibitor, and its two metabolites in patients with advanced solid
      malignancies.
AB  - PURPOSE: To develop a population pharmacokinetic (PK) model for HM781-36
      (poziotinib) and its metabolites in cancer patients. METHODS: Blood samples were
      collected from three phase I studies in which fifty-two patients received oral
      HM781-36B tablets (0.5-32 mg) once daily for 2 weeks, and another 20 patients
      received oral HM781-36B tablets (12, 16, 18, 24 mg) in fasting (12 patients) or
      fed (eight patients) state once daily for 4 weeks. Nonlinear mixed effect
      modeling was employed to develop the population pharmacokinetic model. RESULTS:
      HM781-36 PK was ascribed to a two-compartment model and HM781-36-M1/-M2 PK to one
      compartment model. HM781-36 oral absorption was characterized by first-order
      input (absorption rate constant: 1.45 +/- 0.23 h-1). The central volume of
      distribution (185 +/- 12.7 L) was influenced significantly by body weight. The
      absorption rate constant was influenced by food. The typical HM781-36 apparent
      clearance was 34.5 L/h (29.4 %CV), with an apparent peripheral volume of
      distribution of 164 L (53.5 %CV). Other covariates did not significantly further
      explain the PKs of HM781-36. CONCLUSIONS: The proposed model suggests that HM781
      36 PKs are consistent across most solid tumor types, and that the absorption
      process of HM781-36 is affected by the fed state before dosing. HM781-36 PKs are
      not complicated by patient factors, other than body weight.

PMID- 25377159
TI  - Multiple myeloma after kidney transplantation.
AB  - BACKGROUND: Data regarding multiple myeloma (MM) that develops after kidney
      transplantation (KTx) are scarce. The outcomes of these patients were evaluated
      in a retrospective study. METHODS: Patients with newly diagnosed MM after KTx
      were selected. Patients with a diagnosis of MM or those who received treatment
      for monoclonal gammopathy of renal significance (MGRS) prior to KTx were
      excluded. RESULTS: Between 2001 and 2012, seven patients developed MM after KTx.
      Reasons for ESRD included ADPKD (1), C1q nephropathy (1), MPGN (2), hypertensive
      nephrosclerosis (2), and chronic interstitial nephritis (1). Before KTx, only
      four patients had monoclonal protein studies, four had monoclonal gammopathy of
      undermined significance (MGUS), and two of them had clonal plasma cells in bone
      marrow. Median follow-up after MM was 70 months (range 19-100). Median survival
      was 80 months. Median time from KTx to MM was 72 months (range 3-204 months). The
      Kidney allograft failed in four patients due to monoclonal protein-related renal
      disease. Five patients received chemotherapy: bortezomib (n = 3), lenalidomide (n
      = 2), melphalan (n = 1), thalidomide (n = 1), pomalidomide (n = 1), and high-dose
      dexamethasone (n = 1). Three patients received ASCT. CONCLUSION: Multiple myeloma
      after KTx is rare. Most patients who develop MM had MGUS prior to KTx. There is
      significant renal involvement in these patients. Survival is not worse when
      compared to MM without KTx. Further work is needed to identify the best treatment
      options for these patients.

PMID- 25377160
TI  - Knockdown of cancerous inhibitor of protein phosphatase 2A may sensitize
      metastatic castration-resistant prostate cancer cells to cabazitaxel
      chemotherapy.
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified
      human oncoprotein that can stabilize some proteins by inhibiting degradation
      mediated by protein phosphatase 2A (PP2A), and its level in cancer is associated
      with resistance to chemotherapy. However, whether CIP2A could increase
      chemoresistance of prostate cancer (PCa) cells to chemotherapeutic agent
      cabazitaxel remains unclear. To determine whether CIP2A serves as a potential
      therapeutic target of human PCa, we utilized small interference RNA (siRNA) to
      knock down CIP2A expression in human PCa cells and analyzed their phenotypic
      changes. The data demonstrated that CIP2A was significantly elevated in mCRPC
      cell lines C4-2 and ARCaP(M) at both the mRNA and protein levels. CIP2A silencing
      led to decreased proliferation and enhanced chemosensitivity and apoptosis to
      cabazitaxel in human PCa cells, as well as reduced Akt phosphorylation. Our data
      suggesting critical roles of CIP2A in PCa cells chemoresistance to cabazitaxel
      and raising the possibility of CIP2A inhibition as a promising approach for
      chemosensitization of metastatic castration-resistant prostate cancer (mCRPC).

PMID- 25377161
TI  - Positive expression of pro-opiomelanocortin (POMC) is a novel independent poor
      prognostic marker in surgically resected non-small cell lung cancer.
AB  - This study aims to investigate the expression level of pro-opiomelanocortin
      (POMC) and its prognostic value in non-small cell lung cancer (NSCLC).
      Immunohistochemical staining was used to detect the expression level of POMC.
      Correlations between POMC expression and clinical and pathological
      characteristics were evaluated with the chi-square test, and the prognostic value
      was determined with the Kaplan-Meier method and COX proportional hazards model,
      alpha < 0.05. Of the samples, 48.0% had positive POMC expression. POMC expression
      was significantly related to poorly differentiated tumors, N-stage, p-stage,
      postoperative failure pattern, expression of vimentin, and expression of E
      cadherin (P < 0.05). Multivariate analysis revealed that POMC-positive expression
      was an independent risk factor for disease-free survival (hazard ratio (HR)
      1.988, 95% confidence interval (CI) 1.094-3.910, P = 0.024) and overall survival
      (HR 1.892, 95% CI 1.726-3.709, P = 0.036). The addition of POMC protein
      expression to the prognostic model using pathological stage markedly improved the
      prognostic potential, and the area under the ROC increased from 0.691 to 0.775.
      Further study revealed that patients with POMC-negative expression can benefit
      more from a regimen of paclitaxel and carboplatin chemotherapy than a regimen of
      vinorelbine and carboplatin compared to patients with POMC-positive expression.
      We found that POMC-positive expression is a novel, independent poor prognostic
      marker in patients with NSCLC. Prospective studies are needed to validate the
      potential prognostic value of POMC in combination with the current staging system
      and in consideration of adjuvant chemotherapy.

PMID- 25377163
TI  - Post-thrombolysis hemorrhage risk of unruptured intracranial aneurysms.
AB  - BACKGROUND/AIMS: It has been questioned whether patients with unruptured
      intracranial aneurysms (IAs) are at a greater risk for the development of
      intracerebral hemorrhage (ICH) following thrombolytic therapy. We thus performed
      a meta-analysis to better quantify the risk of post-thrombolysis ICH in patients
      with acute ischemic stroke and incidental IAs. METHODS: We searched PubMed, Web
      of Science and EMBASE for studies assessing ICH risk in patients with acute
      ischemic stroke treated with thrombolysis, in relation to the presence of
      pretreatment IAs. A fixed-effects model meta-analysis was performed. RESULTS: We
      identified four studies totaling 707 participants receiving intravenous
      thrombolysis. The prevalence of unruptured IAs was 6.8%. Pooled analysis
      demonstrates relative risk (RR) for the presence of unruptured IAs and the
      development of any ICH to be 1.204 (95% CI 0.709-2.043; p = 0.492; I(2) = 0.0%).
      The RR for sICH is 1.645 (95% CI 0.453-5.970; p = 0.449; I(2) = 28.1%).
      CONCLUSION: Intravenous thrombolysis was safe among patients with acute ischemic
      stroke and incidental unruptured IAs. Future prospective studies with much larger
      sample sizes are required to clarify the significance of the association between
      pre-existing unruptured IAs and the development of post-thrombolysis ICH.

PMID- 25377162
TI  - Overexpression of SMARCA5 correlates with cell proliferation and migration in
      breast cancer.
AB  - SMARCA5 partners with RSF-1 to compose the RSF complex, which belongs to the ISWI
      family of chromatin remodelers. Recent studies referred that SMARCA5 was
      overexpressed in some malignant tumors. However, expression pattern and
      biological roles of SMARCA5 in breast cancer have not been examined. In the
      present study, we found that SMARCA5 was overexpressed in breast cancer specimens
      by immunohistochemistry. Significant association was observed between SMARCA5
      overexpression and TNM stage (p = 0.0199), tumor size (p = 0.0066), high
      proliferation index (p = 0.0366), and poor overall survival (p = 0.0141). SMARCA5
      overexpression also correlated with Rsf-1 expression levels (p = 0.0120).
      Furthermore, colony formation assay and Matrigel invasion assay showed that
      knockdown of SMARCA5 expression in MDA-MB-231 and MDA-MB-435s cell lines with
      high endogenous expression decreased cell proliferation and cell invasion. Flow
      cytometry showed knockdown of SMARCA5-arrested cell cycle. Further analysis of
      cell cycle and invasion-related molecules showed that SMARCA5 downregulated
      cyclin A, MMP2 expression and upregulated p21 expression. In conclusion, our
      study demonstrated that SMARCA5 was overexpressed in human breast cancers and
      correlated with poor prognosis. SMARCA5 contributes to breast cancer cell
      proliferation and invasion.

PMID- 25377164
TI  - A probabilistic model to investigate the properties of prognostic tools for
      falls.
AB  - BACKGROUND: Falls are a prevalent and burdensome problem in the elderly. Tools
      for the assessment of fall risk are fundamental for fall prevention. Clinical
      studies for the development and evaluation of prognostic tools for falls show
      high heterogeneity in the settings and in the reported results. Newly developed
      tools are susceptible to over-optimism. OBJECTIVES: This study proposes a
      probabilistic model to address critical issues about fall prediction through the
      analysis of the properties of an ideal prognostic tool for falls. METHODS: The
      model assumes that falls occur within a population according to the Greenwood and
      Yule scheme for accident-proneness. Parameters for the fall rate distribution are
      estimated from counts of falls of four different epidemiological studies.
      RESULTS: We obtained analytic formulas and quantitative estimates for the
      predictive and discriminative properties of the ideal prognostic tool. The area
      under the receiver operating characteristic curve (AUC) ranges between about 0.80
      and 0.89 when prediction on any fall is made within a follow-up of one year.
      Predicting on multiple falls results in higher AUC. CONCLUSIONS: The
      discriminative ability of current validated prognostic tools for falls is
      sensibly lower than what the proposed ideal perfect tool achieves. A sensitivity
      analysis of the predictive and discriminative properties of the tool with respect
      to study settings and fall rate distribution identifies major factors that can
      account for the high heterogeneity of results observed in the literature.

PMID- 25377165
TI  - Fronto-temporal connectivity is preserved during sung but not spoken word
      listening, across the autism spectrum.
AB  - Co-occurrence of preserved musical function with language and socio-communicative
      impairments is a common but understudied feature of Autism Spectrum Disorders
      (ASD). Given the significant overlap in neural organization of these processes,
      investigating brain mechanisms underlying speech and music may not only help
      dissociate the nature of these auditory processes in ASD but also provide a
      neurobiological basis for development of interventions. Using a passive-listening
      functional magnetic resonance imaging paradigm with spoken words, sung words and
      piano tones, we found that 22 children with ASD, with varying levels of
      functioning, activated bilateral temporal brain networks during sung-word
      perception, similarly to an age and gender-matched control group. In contrast,
      spoken-word perception was right-lateralized in ASD and elicited reduced inferior
      frontal gyrus (IFG) activity which varied as a function of language ability.
      Diffusion tensor imaging analysis reflected reduced integrity of the left
      hemisphere fronto-temporal tract in the ASD group and further showed that the
      hypoactivation in IFG was predicted by integrity of this tract. Subsequent
      psychophysiological interactions revealed that functional fronto-temporal
      connectivity, disrupted during spoken-word perception, was preserved during sung
      word listening in ASD, suggesting alternate mechanisms of speech and music
      processing in ASD. Our results thus demonstrate the ability of song to overcome
      the structural deficit for speech across the autism spectrum and provide a
      mechanistic basis for efficacy of song-based interventions in ASD.

PMID- 25377166
TI  - Randomized comparison of experts and trainees with nasal and oral fibreoptic
      intubation in children less than 2 yr of age.
AB  - BACKGROUND: We hypothesized that the time to successful fibreoptic tracheal
      intubation through the nasal route would be faster than the oral route for both
      experts and trainees in children <2 yr of age. METHODS: One hundred children, 24
      months and under in age, were randomized to an operator (expert or trainee), and
      route (nasal or oral) for fibreoptic tracheal intubation. Three separate times
      were then measured: (i) time to first glottic view, (ii) time to carinal view,
      and (iii) total time to successful tracheal intubation. The number of attempts
      made, manoeuvres needed to obtain an adequate laryngeal view, and manoeuvres for
      tracheal tube passage were also recorded. RESULTS: Time to successful tracheal
      intubation was significantly faster for experts than trainees. There was no
      difference in the time to tracheal intubation between the nasal and oral routes
      for experts. In trainees, intubation times were shorter for the nasal route
      median (inter-quartile range) time (s) to carinal view was 35 (27-63) for the
      nasal route vs 59 (38-94) for the oral route (P=0.03), and the median time to
      successful tracheal intubation were 62 (49-122) vs 117 (61-224), P=0.05, for the
      nasal and oral routes, respectively. For trainees, the oral route required a
      greater number of airway manoeuvres for adequate laryngeal views and passage of
      the tracheal tube compared with the nasal route. CONCLUSIONS: For clinicians with
      less experience in using paediatric bronchoscopes, fibreoptic tracheal intubation
      through the nasal route may be a more straightforward process than the oral route
      in children <2 yr of age. CLINICAL TRIAL REGISTRATION: NCT02029300
      (www.clinicaltrials.gov).

PMID- 25377167
TI  - The Role of Surface Similarity in Analogical Retrieval: Bridging the Gap Between
      the Naturalistic and the Experimental Traditions.
AB  - Blanchette and Dunbar (2000) have claimed that when participants are allowed to
      draw on their own source analogs in the service of analogical argumentation,
      retrieval is less constrained by surface similarity than traditional experiments
      suggest. In two studies, we adapted this production paradigm to control for the
      potentially distorting effects of analogy fabrication and uneven availability of
      close and distant sources in memory. Experiment 1 assessed whether participants
      were reminded of central episodes from popular movies while generating analogies
      for superficially similar versus superficially dissimilar target situations. In
      Experiment 2, we modified this procedure to assess the retrieval of
      autobiographic memories, more familiar to participants than fictional episodes.
      Both studies revealed a strong effect of surface similarity on the retrieval of
      participants' own sources, thus suggesting that the superficial bias typically
      observed in experimental studies--and simulated by most computational models-
      does not originate in a lack of ecological validity.

PMID- 25377168
TI  - Spinal clear cell meningioma in a 3-year-old: a case report.
AB  - Clear cell meningioma (CCM) is an aggressive meningioma variant with a tendency
      to early recurrence posing a challenge to its treatment. Although spinal
      meningiomas are uncommon in children, this rare entity has been described as the
      most common variant of spinal meningiomas in the pediatric age group. We present
      the case of a 3-year-old with a confirmed lumbar spine CCM and discuss the
      problems encountered in the management of this disease.

PMID- 25377169
TI  - Representative mammalian cell culture test materials for assessment of primary
      recovery technologies: a rapid method with industrial applicability.
AB  - Mammalian cell culture material is often difficult to produce accurately and
      reproducibly for downstream studies. This article presents a methodology for the
      creation of a set of cell culture test materials where key variables including
      cell density, cell viability, product, and the host cell protein (HCP) load can
      be manipulated individually. The methodology was developed using a glutamine
      synthetase Chinese hamster ovary cell line cultured at 5-L and 70-L scales. Cell
      concentration post-cell growth was manipulated using tangential flow filtration
      to generate a range of target cell densities of up to 100 * 10(6) cells/mL. A
      method to prepare an apoptotic cell stock to achieve target viabilities of 40-90%
      is also described. In addition, a range of IgG1 and HCP concentrations was
      achieved. The results illustrate that the proposed methodology is able to mimic
      different cell culture profiles by decoupling the control of the key variables.
      The cell culture test materials were shown to be representative of typical cell
      culture feed material in terms of particle size distribution and HCP population.
      This provides a rapid method to create the required feeds for assessing the
      feasibility of primary recovery technologies designed to cope with higher cell
      density cultures. 

PMID- 25377170
TI  - T. Kishi and N. Iwata: Varenicline for smoking cessation in people with
      schizophrenia: systematic review meta-analysis.

PMID- 25377172
TI  - Di- and trinuclear gold complexes of diphenylphosphinoethyl-functionalised
      imidazolium salts and their N-heterocyclic carbenes: synthesis and photophysical
      properties.
AB  - Diphenylphosphinoethyl-functionalised imidazolium salts and their silver-carbene
      complexes were used to synthesise a series of di- and trinuclear gold complexes
      through ligand exchange and transmetallation, respectively. Besides a few
      positively charged macrocyclic compounds with different anions (both with and
      without activation of the carbene function), we were able to obtain neutral
      polynuclear complexes by varying the gold precursor. The synthesised gold
      complexes show a variety of photophysical properties, including bright white
      photoluminescence at ambient temperature. 

PMID- 25377171
TI  - Prevalence of diabetes and impaired fasting glucose among residents in the Three
      Gorges Reservoir Region, China.
AB  - BACKGROUND: The Three Gorges Dam in China is the world's largest hydro-electric
      scheme in the contemporary world. After the construction of the Dam, great
      changes took place on the residents' lifestyles characterized by reduced physical
      activity due to the loss of arable land and a series of psychological problems
      caused by resettlement, which might be regarded as contributing factors to the
      development of diabetes in Three Gorges Reservoir Region (TGRR). However, there
      is no study that has been conducted targeting large population samples with the
      aim of determining the prevalence of diabetes in TGRR. This study purposed to
      estimate the prevalence of diabetes and impaired fasting glucose (IFG) in the
      adult population >=18 years in TGRR and to evaluate the associated risk factors.
      METHODS: A total of 3721 randomly selected adults, aged >=18 years and having
      lived in TGRR for at least one year, participated in questionnaire-based
      interview from April to May 2013 and had their physical examinations and standard
      glucose taken. 75 g oral glucose tolerance test (OGTT) was conducted on the
      subjects with fasting glucose levels being >= 5.6 mmol/L. Diabetes and IFG were
      defined according to WHO 1999 criteria. RESULTS: The age-standardized prevalence
      of diabetes and IFG were 7.6% (7.9% among men and 7.4% among women) and 9.0%
      (9.1% among men and 8.9% among women), respectively. Among the identified cases
      of diabetes in this study, 54.46% (171/314) were newly diagnosed. The prevalence
      of diabetes cases rose with age (4.0%, 4.5%, 8.1%, 11.2%, 12.4% and 12.9% among
      persons who were 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69 and >= 70 years
      of age, respectively). The results of multivariate logistic-regression analyses
      showed that the diabetes was significantly linked to age, family history of
      diabetes, central obesity, educational level and hypertension for both men and
      women. In addition, smoking was significantly associated with diabetes in men.
      CONCLUSIONS: Diabetes has become a major public health problem in the TGRR with a
      large number of the cases undiagnosed. These results suggest that regular
      population-based diabetes screening should be conducted to identify early-stage
      diabetes and integrated strategies aimed at the prevention and treatment of
      diabetes initiated.

PMID- 25377174
TI  - An integrated computational tool to model the broadening of the absorption bands
      of flexible dyes in solution: cationic chromophores as test cases.
AB  - This paper is devoted to the development and application of an effective
      computational approach for the prediction of band broadening in the electronic
      spectra of semi-flexible organic molecules in solution. The protocol is based on
      DFT, TD-DFT, and PCM computational techniques and attempts to take into account
      the three main contributions tuning electronic spectra, namely vibronic
      transitions, conformational equilibria, and solvent relaxation. The whole
      procedure has been implemented in the Gaussian code and has been tested for the
      interpretation of the spectroscopic behaviour of a betainic dye and a series of
      charged dyes, containing one methyl-pyridinium or quinolinium group and a
      flexible moiety. The results provide a comprehensive picture of solvatochromic
      effects and offer a reliable answer to the open problem of the origin of band
      broadening in the target semi-flexible dyes. 

PMID- 25377173
TI  - Mad linker phosphorylations control the intensity and range of the BMP-activity
      gradient in developing Drosophila tissues.
AB  - The BMP ligand Dpp, operates as a long range morphogen to control many important
      functions during Drosophila development from tissue patterning to growth. The BMP
      signal is transduced intracellularly via C-terminal phosphorylation of the BMP
      transcription factor Mad, which forms an activity gradient in developing
      embryonic tissues. Here we show that Cyclin dependent kinase 8 and Shaggy
      phosphorylate three Mad linker serines. We demonstrate that linker
      phosphorylations control the peak intensity and range of the BMP signal across
      rapidly developing embryonic tissues. Shaggy knockdown broadened the range of the
      BMP-activity gradient and increased high threshold target gene expression in the
      early embryo, while expression of a Mad linker mutant in the wing disc resulted
      in enhanced levels of C-terminally phosphorylated Mad, a 30% increase in wing
      tissue, and elevated BMP target genes. In conclusion, our results describe how
      Mad linker phosphorylations work to control the peak intensity and range of the
      BMP signal in rapidly developing Drosophila tissues. 

PMID- 25377175
TI  - Optimizing methods for the study of intravascular lipid metabolism in zebrafish.
AB  - The zebrafish (Danio rerio) is a useful vertebrate model for use in
      cardiovascular drug discovery. The present study aimed to construct optimized
      methods for the study of intravascular lipid metabolism of zebrafish. The
      lipophilic dye, Oil Red O, was used to stain fasting zebrafish one to eight days
      post-fertilization (dpf) and to stain 7-dpf zebrafish incubated in a breeding
      system containing 0.1% egg yolk as a high-fat diet (HFD) for 48 h. Three-dpf
      zebrafish were kept in CholEsteryl boron-dipyrromethene (BODIPY) 542/563 C11
      water for 24 h which indicated the efficiency of CholEsteryl BODIPY 542/563 C11
      intravascular cholesterol staining. Subsequently, 7-dpf zebrafish were incubated
      in water containing the fluorescent probe CholEsteryl BODIPY 542/563 C11 and fed
      a high-cholesterol diet (HCD) for 10 d. Two groups of 7-dpf zebrafish were
      incubated in regular breeding water and fed with a regular or HCD containing
      CholEsteryl BODIPY 542/563 C11 for 10 d. Finally, blood lipids of adult zebrafish
      fed with regular or HFD for seven weeks were measured. Oil Red O was not detected
      in the blood vessels of 7-8-dpf zebrafish. Increased intravascular lipid levels
      were detected in 7-dpf zebrafish incubated in 0.1% egg yolk, indicated by Oil Red
      O staining. Intravascular cholesterol was efficiently stained in 3-dpf zebrafish
      incubated in breeding water containing CholEsteryl BODIPY 542/563 C11; however,
      this method was inappropriate for the calculation of intravascular fluorescence
      intensity in zebrafish >7-dpf. In spite of this, intra-aortic fluorescence
      intensity of zebrafish fed a HCD containing CholEsteryl BODIPY 542/563 C11 was
      significantly higher (P<0.05) than that of those fed a regular diet containing
      CholEsteryl BODIPY 542/563 C11. The serum total cholesterol and triglyceride
      levels of adult zebrafish fed a HFD were markedly increased compared to those of
      the control group (P<0.05). In conclusion, the use of Oil Red O staining and
      CholEsteryl BODIPY 542/563 C11 may have applications in zebrafish intravascular
      lipid metabolism research and screens for novel lipid-regulating drugs.

PMID- 25377176
TI  - Aplysin induces apoptosis in glioma cells through HSP90/AKT pathway.
AB  - Glioma is one of the most common malignancies in the world. However, an effective
      regiment is lacking. Increasing evidence indicated that PI3K/AKT signaling is
      critical for the survival of glioma. In this study, we aimed to study the effect
      of aplysin on the survival and proliferation of GL26 glioma cells and the
      involved mechanisms. The data showed that aplysin suppressed the viability of
      glioma cells in both dose- and time-dependent manners. It also induced G0/G1
      arrest and apoptosis in glioma cells. Western blot assays revealed that aplysin
      treatment changed p-AKT expression by impairing the formation of Heat shock
      protein 90/AKT complex. Aplysin significantly increased the survival time of mice
      bearing glioma and reduced the weights of the established gliomas. Collectively,
      aplysin can inhibit the proliferation of GL26 glioma cells and induce apoptosis
      in vitro, perhaps through suppressing PI3K/AKT pathway. It can also inhibit
      glioma growth in vivo and prolong the survival of mice. Thus, aplysin may be a
      novel therapeutic drug for glioma.

PMID- 25377177
TI  - The Global Consortium for Drug-resistant Tuberculosis Diagnostics (GCDD): design
      of a multi-site, head-to-head study of three rapid tests to detect extensively
      drug-resistant tuberculosis.
AB  - BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a threat to global public
      health, owing to the complexity and delay of diagnosis and treatment. The Global
      Consortium for Drug-resistant Tuberculosis Diagnostics (GCDD) was formed to
      develop and evaluate assays designed to rapidly detect DR-TB, so that appropriate
      treatment might begin more quickly. This paper describes the methodology employed
      in a prospective cohort study for head-to-head assessment of three different
      rapid diagnostic tools. METHODS: Subjects at risk of DR-TB were enrolled from
      three countries. Data were gathered from a combination of patient interviews,
      chart reviews, and laboratory testing from each site's reference laboratory. The
      primary outcome of interest was reduction in time from specimen arrival in the
      laboratory to results of rapid drug susceptibility tests, as compared with
      current standard mycobacterial growth indicator tube (MGIT) drug susceptibility
      tests. RESULTS: Successful implementation of the trial in diverse multinational
      populations is explained, in addition to challenges encountered and
      recommendations for future studies with similar aims or populations. CONCLUSIONS:
      The GCDD study was a head-to-head study of multiple rapid diagnostic assays aimed
      at improving accuracy and precision of diagnostics and reducing overall time to
      detection of DR-TB. By conducting a large prospective study, which captured
      epidemiological, clinical, and biological data, we have produced a high-quality
      unique dataset, which will be beneficial for analyzing study aims as well as
      answering future DR-TB research questions. Reduction in detection time for XDR-TB
      would be a major public health success as it would allow for improved treatment
      and more successful patient outcomes. Executing successful trials is critical in
      assessment of these reductions in highly variable populations. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02170441.

PMID- 25377178
TI  - The diversification and activity of hAT transposons in Musa genomes.
AB  - Sequencing of plant genomes often identified the hAT superfamily as the largest
      group of DNA transposons. Nevertheless, detailed information on the diversity,
      abundance and chromosomal localization of plant hAT families are rare. By in
      silico analyses of the reference genome assembly and bacterial artificial
      chromosome (BAC) sequences, respectively, we performed the classification and
      molecular characterization of hAT transposon families in Musa acuminata. Musa hAT
      transposons are organized in three families designated MuhAT I, MuhAT II and
      MuhAT III. In total, 70 complete autonomous elements of the MuhAT I and MuhAT II
      families were detected, while no autonomous MuhAT III transposons were found.
      Based on the terminal inverted repeat (TIR)-specific sequence information of the
      autonomous transposons, 1722 MuhAT I- and MuhAT II-specific miniature inverted
      repeat transposable elements (MuhMITEs) were identified. Autonomous MuhAT I and
      MuhAT II elements are only moderately abundant in the sections of the genus Musa,
      while the corresponding MITEs exhibit an amplification in Musa genomes. By
      fluorescent in situ hybridization (FISH), autonomous MuhAT transposons as well as
      MuhMITEs were localized in subtelomeric, most likely gene-rich regions of M.
      acuminata chromosomes. A comparison of homoeologous regions of M. acuminata and
      Musa balbisiana BACs revealed the species-specific mobility of MuhMITEs. In
      particular, the activity of MuhMITEs II showing transduplications of genomic
      sequences might indicate the presence of active MuhAT transposons, thus
      suggesting a potential role of MuhMITEs as modulators of genome evolution of
      Musa. 

PMID- 25377179
TI  - An integrated assessment for wind energy in Lake Michigan coastal counties.
AB  - The benefits and challenges of onshore and offshore wind energy development were
      assessed for a 4-county area of coastal Michigan. Economic, social,
      environmental, and spatial dimensions were considered. The coastal counties have
      suitable wind resources for energy development, which could contribute toward
      Michigan's 10% renewable energy standard. Wind energy is cost-effective with
      contract prices less than the benchmark energy price of a new coal-fired power
      plant. Constructing a 100 MW wind farm could have a $54.7 million economic
      impact. A patchwork of township-level zoning ordinances regulates wind energy
      siting. Voluntary collaborations among adjacent townships standardizing the
      ordinances could reduce regulatory complexity. A Delphi Inquiry on offshore wind
      energy in Lake Michigan elicited considerable agreement on its challenges, but
      little agreement on the benefits to coastal communities. Offshore turbines could
      be acceptable to the participants if they reduced pollution, benefited coastal
      communities, involved substantial public participation, and had minimal impact on
      property values and tourism. The US Coast Guard will take a risk-based approach
      to evaluating individual offshore developments and has no plans to issue blanket
      restrictions around the wind farms. Models showed that using wind energy to reach
      the remainder of the 10% renewable energy standard could reduce SO2 , NOx , and
      CO2 pollution by 4% to 7%. Turbines are highly likely to impact the area's
      navigational and defense radar systems but planning and technological upgrades
      can reduce the impact. The integrated assessment shows that responsible wind
      energy development can enhance the quality of life by reducing air pollution and
      associated health problems and enhancing economic development. Policies could
      reduce the negative impacts to local communities while preserving the benefits to
      the broader region.

PMID- 25377181
TI  - Long-acting local anesthetic agents and additives: snake oil, voodoo, or the real
      deal?

PMID- 25377180
TI  - Concise reviews: Assisted reproductive technologies to prevent transmission of
      mitochondrial DNA disease.
AB  - While the fertilized egg inherits its nuclear DNA from both parents, the
      mitochondrial DNA is strictly maternally inherited. Cells contain multiple copies
      of mtDNA, each of which encodes 37 genes, which are essential for energy
      production by oxidative phosphorylation. Mutations can be present in all, or only
      in some copies of mtDNA. If present above a certain threshold, pathogenic mtDNA
      mutations can cause a range of debilitating and fatal diseases. Here, we provide
      an update of currently available options and new techniques under development to
      reduce the risk of transmitting mtDNA disease from mother to child.
      Preimplantation genetic diagnosis (PGD), a commonly used technique to detect
      mutations in nuclear DNA, is currently being offered to determine the mutation
      load of embryos produced by women who carry mtDNA mutations. The available
      evidence indicates that cells removed from an eight-cell embryo are predictive of
      the mutation load in the entire embryo, indicating that PGD provides an effective
      risk reduction strategy for women who produce embryos with low mutation loads.
      For those who do not, research is now focused on meiotic nuclear transplantation
      techniques to uncouple the inheritance of nuclear and mtDNA. These approaches
      include transplantation of any one of the products or female meiosis (meiosis II
      spindle, or either of the polar bodies) between oocytes, or the transplantation
      of pronuclei between fertilized eggs. In all cases, the transferred genetic
      material arises from a normal meiosis and should therefore, not be confused with
      cloning. The scientific progress and associated regulatory issues are discussed.

PMID- 25377182
TI  - A comparison of fibrinogen measurement using TEG((r)) functional fibrinogen and
      Clauss in cardiac surgery patients.
AB  - INTRODUCTION: Viscoelastic methods of estimating fibrinogen measure clot
      formation under platelet inhibition; these methods are gaining in popularity
      because of their convenience and speed. The aim of this study was to compare the
      results of the TEG((r)) functional fibrinogen (FF) assay with the Clauss
      fibrinogen method in a group of patients presenting for cardiac surgery and to
      assess whether they gave equivalent results. METHODS: As part of a larger study
      evaluation a transfusion algorithm for use in cardiac surgery, 320 paired samples
      of TEG((r)) FF and Clauss fibrinogen were compared. These were taken from 160
      patients undergoing cardiac surgery at two time points - prior to heparinisation
      and 10 min after the administration of protamine. The results of the two
      fibrinogen measurements were also analysed in relation to the platelet count at
      the time. RESULTS: There was no significant correlation between the TEG((r)) FLEV
      and Clauss fibrinogen at baseline (R(2) = 0.106) or 10 min postprotamine (R(2) =
      0.025) The TEG((r)) FF maximal amplitude and the Clauss were also found to have
      no significant correlation (at baseline R(2) = 0.061), at 10 min postprotamine
      (R(2) = 0.260). Bland-Altman analysis showed no significant agreement between the
      two methods. CONCLUSION: The TEG((r)) FF does not produce results equivalent to
      those of the Clauss fibrinogen regardless of platelet count.

PMID- 25377183
TI  - Innate immune proteins as biomarkers for CNS injury: critical evaluation
      (WO2013119673 A1).
AB  - INTRODUCTION: Injuries to the CNS represent a major global health problem. CNS
      injuries cause the elevation of many proteins, including innate immune proteins
      in biological fluids, such as the cerebrospinal fluid (CSF). These innate immune
      proteins can be considered as biomarkers to predict the severity of CNS injury in
      patients. AREAS COVERED: This invention describes a method for the
      diagnosis/prognosis, treatment or rehabilitation efforts, and monitoring of post
      treatment responses after CNS injuries in a patient, based on the detection and
      quantification of the expression levels of protein components of inflammasomes in
      the CSF. This study evaluates the elevated levels of inflammasome proteins such
      as NLRP1 (NAcht leucine-rich-repeat protein 1), ASC and caspase-1 in biological
      samples as important biomarkers that can assess the extent of neuroinflammation
      and reflect the magnitude of inflammation-induced damage following CNS injury.
      EXPERT OPINION: Although inflammasome proteins may be of great clinical
      significance in the near future, a more detailed analysis of inflammasome
      proteins needs to be taken into account for the prognosis and treatment of
      diverse CNS conditions. Moreover, the potential inflammasome biomarker candidates
      have to be validated in a large number of patients for an extended period post
      injury to further support clinical relevance.

PMID- 25377185
TI  - Gold(I)-alkanethiolate nanotubes.
AB  - A solution approach to assembling Au(I)-alkanethiolates into nanotube structures
      at room temperature is presented, in which Au(I) cations and alkanethiolate
      ligands are coordinated into thin platelet forms that then evolve into an open
      tubular configuration. The organic-inorganic hybrid nature of the nanotubes,
      their ability to be modified, and their high stability make them of interest for
      practical applications. 

PMID- 25377184
TI  - Effects of hypertonic buffer composition on lymph node uptake and bioavailability
      of rituximab, after subcutaneous administration.
AB  - The subcutaneous administration of biologics is highly desirable; however,
      incomplete bioavailability after s.c. administration remains a major challenge.
      In this work we investigated the effects of excipient dependent hyperosmolarity
      on lymphatic uptake and plasma exposure of rituximab as a model protein. Using
      Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl,
      mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab
      over 5 days after s.c. administration. An increase was observed in plasma
      concentrations in animals administered rituximab in hypertonic buffer solutions,
      compared with isotonic buffer. Bioavailability, as estimated by our
      pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic
      buffer containing NaCl, to almost complete bioavailability in hypertonic buffers
      containing high dose OPLS or mannitol. This improvement in plasma exposure is due
      to the improved lymphatic trafficking as evident from the increase in the
      fraction of dose trafficked through the lymph nodes in the presence of hypertonic
      buffers. The fraction of the dose trafficked through the lymphatics, as estimated
      by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer
      containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and
      mannitol. The data suggest that hypertonic solutions may be a viable option for
      improving s.c. bioavailability.

PMID- 25377186
TI  - Pretreatment With Caffeine Citrate to Increase Seizure Duration During
      Electroconvulsive Therapy: A Case Series.
AB  - OBJECTIVE: Due to the shortage of parenteral caffeine and sodium benzoate,
      patients were pretreated with caffeine citrate to increase therapeutic seizure
      duration during electroconvulsive therapy (ECT). To date, no data are available
      on the use of caffeine citrate during ECT. This retrospective case series was
      done to demonstrate utilization of caffeine citrate as a substitute for caffeine
      and sodium benzoate in optimizing ECT. METHOD: Medical records were reviewed to
      identify patients who received ECT and caffeine citrate. Physician notes were
      reviewed to determine the parameters of the ECT procedure, the seizure length,
      and the dose of caffeine citrate. Each chart was thoroughly studied to find the
      relationship between seizure duration and dose of caffeine citrate. RESULTS: Of
      the 12 ECT treatments utilizing caffeine citrate, 9 achieved at least 1 session
      lasting >30 seconds with an average seizure duration of 35 seconds. Increase in
      seizure duration ranged from -41% to 276% with an average increase of 48%. Only 3
      treatment sessions utilizing caffeine citrate showed no increase in seizure
      duration. Doses ranged from 120 to 600 mg of both oral and parenteral caffeine
      citrate. Although increase in seizure duration was achieved for the majority of
      the ECT sessions, no dose-response correlation could be made. No significant
      adverse reactions were noted with the use of caffeine citrate during ECT.
      CONCLUSION: It was determined that, much like caffeine and sodium benzoate,
      caffeine citrate does increase the seizure duration. However, this response did
      vary due to many reasons including small sample size, concomitant medications,
      duration of illness, and number of ECTs they received in the past and how long
      ago they received the last ECT. Further research is required to elucidate the
      effect of these variables on seizure duration.

PMID- 25377187
TI  - Efficacy and safety of prophylactic treatment with plasma-derived factor XIII
      concentrate (human) in patients with congenital factor XIII deficiency.
AB  - Congenital factor XIII (FXIII) deficiency is an extremely rare, potentially life
      threatening bleeding disorder. Routine prophylactic management is recommended for
      individuals with clinically relevant FXIII deficiency. This prospective,
      multicentre, open-label study evaluated the long-term efficacy and safety of
      prophylactic infusions of FXIII concentrate (human) 40 IU kg(-1) in patients with
      congenital FXIII deficiency. FXIII concentrate (human) was administered every 4
      weeks for 12 months. Dosing was adjusted to maintain trough FXIII activity levels
      of 5-20%. Logistical and ethical constraints precluded use of a placebo control
      group. Annualized incidence of spontaneous bleeding was compared with historical
      rates; safety was assessed as a secondary objective. Forty-one patients were
      enrolled and completed the study. The annualized rate for spontaneous bleeding
      episodes requiring FXIII treatment was 0.000 episodes per patient-year (95% CI:
      0.000; 0.097). The study met its primary endpoint: the upper limit of the 95% CI
      was substantially below the historical rate of 2.5 bleeding episodes per patient
      year. Five spontaneous bleeding episodes (involving three patients; none
      requiring FXIII treatment) and eight trauma-related bleeding episodes (two
      requiring FXIII treatment) occurred. Five patients had surgery during the study,
      only one of whom required FXIII treatment for post-surgical bleeding. Most
      patients (>= 85%) had trough FXIII activity levels >= 10%. No patient
      discontinued treatment due to an adverse event. No adverse events related to
      thromboembolism or viral transmission were reported. Prophylactic treatment with
      FXIII concentrate (human) was well tolerated and prevented spontaneous bleeding
      episodes that were serious enough to require treatment with FXIII-containing
      product. CLINICAL TRIAL REGISTRATION:
      www.clinicaltrials.gov/ct2/show/NCT00885742.

PMID- 25377188
TI  - Near-death experience: arising from the borderlands of consciousness in crisis.
AB  - Brain activity explains the essential features of near-death experience,
      including the perceptions of envelopment by light, out-of-body, and meeting
      deceased loved ones or spiritual beings. To achieve their fullest expression,
      such near-death experiences require a confluence of events and draw upon more
      than a single physiological or biochemical system, or one anatomical structure.
      During impaired cerebral blood flow from syncope or cardiac arrest that commonly
      precedes near-death, the boundary between consciousness and unconsciousness is
      often indistinct and a person may enter a borderland and be far more aware than
      is appreciated by others. Consciousness can also come and go if blood flow rises
      and falls across a crucial threshold. During crisis the brain's prime biologic
      purpose to keep itself alive lies at the heart of many spiritual experiences and
      inextricably binds them to the primal brain. Brain ischemia can disrupt the
      physiological balance between conscious states by leading the brainstem to blend
      rapid eye movement (REM) and waking into another borderland of consciousness
      during near-death. Evidence converges from many points to support this notion,
      including the observation that the majority of people with a near-death
      experience possess brains predisposed to fusing REM and waking consciousness into
      an unfamiliar reality, and are as likely to have out-of-body experience while
      blending REM and waking consciousness as they are to have out-of-body experience
      during near-death. 

PMID- 25377189
TI  - Diagnostic accuracy of 3.0 T magnetic resonance imaging for the detection of
      meniscus posterior root pathology.
AB  - PURPOSE: The purpose of this study was to determine the diagnostic accuracy of 3
      T MRI, including sensitivity, specificity, negative and positive predictive
      values, for detection of posterior medial and lateral meniscus root tears and
      avulsions. METHODS: All patients who had a 3 T MRI of the knee, followed by
      arthroscopic surgery, were included in this study. Arthroscopy was considered the
      gold standard. Meniscus root tears diagnosed at arthroscopy and on MRI were
      defined as a complete meniscus root detachment within 9 mm of the root. All
      surgical data were collected prospectively and stored in a data registry. MRI
      exams were reported prospectively by a musculoskeletal radiologist and reviewed
      retrospectively. RESULTS: There were 287 consecutive patients (156 males, 131
      females; mean age 41.7 years) in this study. Prevalence of meniscus posterior
      root tears identified at arthroscopy was 9.1, 5.9% for medial and 3.5% for
      lateral root tears (one patient had both). Sensitivity was 0.770 (95% CI 0.570,
      0.901), specificity was 0.729 (95% CI 0.708, 0.741), positive predictive value
      was 0.220 (95% CI 0.163, 0.257) and negative predictive value was 0.970 (95% CI
      0.943, 0.987). For medial root tears, sensitivity was 0.824 (95% CI 0.569,
      0.953), specificity was 0.800 (95% CI 0.784, 0.808), positive predictive value
      was 0.206 (95% CI 0.142, 0.238) and negative predictive value was 0.986 (95% CI
      0.967, 0.996). For lateral meniscus posterior root tears, sensitivity was 0.600
      (95% CI 0.281, 0.860), specificity was 0.903 (95% CI 0.891, 0.912), positive
      predictive value was 0.181 (95% CI 0.085, 0.261) and negative predictive value
      was 0.984 (95% CI 0.972, 0.994). CONCLUSIONS: This study demonstrated moderate
      sensitivity and specificity of 3 T MRI to detect posterior meniscus root tears.
      The negative predictive value of 3 T MRI to detect posterior meniscus root tears
      was high; however, the positive predictive value was low. Sensitivity was higher
      for medial root tears, indicating a higher risk of missing lateral root tears on
      MRI. Imaging has an important role in identifying meniscus posterior horn root
      tears; however, some root tears may not be identified until arthroscopy. LEVEL OF
      EVIDENCE: Prognostic study (diagnostic), Level II.

PMID- 25377190
TI  - Mechanostimulation changes the catabolic phenotype of human dedifferentiated
      osteoarthritic chondrocytes.
AB  - PURPOSE: The treatment of cartilage defects with matrix-embedded autologous
      chondrocytes is a promising method to support the repair process and to foster
      reconstitution of full functionality of the joint. METHODS: Human osteoarthritic
      chondrocytes were harvest from nine different patients (mean +/- SD age 68 +/- 8
      years) who underwent total knee replacement. The chondrocytes were embedded after
      a precultivation phase into a collagen I hydrogel. Mid-term intermitted
      mechanostimulation on matrix-embedded dedifferentiated human osteoarthritic
      chondrocytes was performed by intermittently applying a cyclic sinusoid
      compression regime for 4 days (cycles of 1 h of sinusoidal stimulation (1 Hz) and
      4 h of break; maximum compression 2.5%). Stimulated (Flex) and non-stimulated (No
      Flex) cell matrix constructs were analysed concerning the expression of genes
      involved in tissue metabolism, the content of sulphated glycosaminoglycans (sGAG)
      and the morphology of the chondrocytes. RESULTS: Gene expression analysis showed
      a high significant increase in collagen type II expression (p < 0.001), a
      significant increase in aggrecan expression (p < 0.04) and a high significant
      decrease in MMP-13 expression (p < 0.001) under stimulation condition compared
      with unstimulated controls. No significant changes were found in the gene
      expression rate of MMP-3. This positive effect of the mechanostimulation was
      confirmed by the analyses of sGAG. Mechanically stimulated cell-matrix constructs
      had nearly tripled sGAG content than the non-stimulated control (p < 0.002). In
      addition, histological examination showed that morphology of chondrocytes was
      altered from a spindle-shaped to a chondrocyte-characteristic rounded phenotype.
      CONCLUSION: Mid-term intermitted mechanical stimulation in vitro has the
      potential to improve the cell quality of cell matrix constructs prepared from
      dedifferentiated osteoarthritic chondrocytes. This observation may extend the
      inclusion criteria for matrix-assisted autologous chondrocyte implantation (MACI)
      and confirms the importance of moderate dynamic compression in clinical
      rehabilitation after MACI.

PMID- 25377193
TI  - Spain explains reasons for euthanasia of Ebola nurse's dog.

PMID- 25377191
TI  - Platelet-rich plasma for open meniscal repair in young patients: any benefit?
AB  - PURPOSE: Many studies have demonstrated that injection of various growth factors
      including platelet-derived growth factor could increase meniscal cell activity
      and stimulate repair. The purpose of this study was to augment repair and promote
      meniscal healing by the use of platelet-rich plasma (PRP) within horizontal
      cleavage meniscal tears repaired via an open approach. The hypothesis was that
      the clinical outcomes and healing process would be improved using this meniscal
      healing augmentation technique. METHODS: In this case-control study, 34
      consecutive young patients underwent an open meniscal repair to treat symptomatic
      Grade 2 or Grade 3 horizontal meniscal tears [median age 28 years (13-40)]. The
      median time between the onset of symptoms and surgery was 11.5 months (6-50). In
      the first group (17 consecutive patients, Group 1), a standard open meniscal
      repair was performed. In the second group (17 consecutive patients, Group 2), the
      same surgical repair was performed, but platelet-rich plasma was introduced into
      the lesion at the end of the procedure. Clinical outcomes were evaluated using
      KOOS and IKDC 2000 scores. MRI was performed at 1 year after surgery for
      objective evaluation. RESULTS: At a minimum of 24 months postoperatively (mean
      32.2 months, 24-40), three patients underwent subsequent meniscectomy (two in
      Group 1, one in Group 2). The mean KOOS distribution (pain, symptoms, daily
      activities, sports, quality of life) was 78.4, 86.1, 93.8, 74.4, 74.6 in Group 1,
      and 93.3, 90.7, 97.1, 88.8, 78.3 in Group 2 (p < 0.05 for pain and sports
      parameters). MRI revealed five cases with the complete disappearance of any
      hypersignal within the repaired meniscus in Group 2, and none in Group 1 (p <
      0.01). CONCLUSIONS: Open meniscal repair of horizontal tears extending into the
      avascular zone was effective at midterm follow-up in young patients. Clinical
      outcomes were slightly improved by the addition of PRP in this case-control
      study. LEVEL OF EVIDENCE: III.

PMID- 25377192
TI  - Intraoperative laxity measurements using a navigation system in anatomical double
      bundle posterior cruciate ligament reconstruction.
AB  - PURPOSE: The objective of this study was to evaluate knee kinematics during
      double-bundle posterior cruciate ligament reconstruction (DB-PCLR)
      intraoperatively using a navigation system, and especially assess biomechanical
      behaviour of the anterolateral bundle (ALB) and posteromedial bundle (PMB) graft
      in DB-PCLR. Also, clinical results of minimum 2-year follow-up were investigated.
      METHODS: Nine patients received DB-PCLR with hamstring graft. Before
      reconstruction, knee laxities, including posterior tibial translation (PTT) in
      neutral rotation at 15 degrees , 30 degrees , 45 degrees , 60 degrees , 75
      degrees  and 90 degrees  of knee flexion, were measured using a kinematic-based
      navigation system. After the PMB or ALB was temporally fixed, the knee laxities
      were measured in the same manner. Each patient was evaluated pre- and post
      operatively with side-to-side difference of tibial position in gravity sag view
      and Lysholm score. RESULTS: Both ALB and PMB fixation restrained the PTT compared
      to  PCL deficiency throughout all knee flexion angles. At 90 degrees  of knee
      flexion, ALB fixation significantly decreased PTT compare to PMB fixation (p =
      0.014) and DB-PCLR significantly decreased PTT compare to ALB fixation (p =
      0.045). The mean side-to-side difference of tibial position in gravity sag view
      was 12.0 +/- 1.7 mm preoperatively and 2.3 +/- 1.8 mm at final follow-up, and the
      mean Lysholm scores were 68.9 +/- 20.9 and 96.3 +/- 2.9, respectively.
      CONCLUSIONS: There were no significant differences in the PTT between ALB and PMB
      fixations at 0 degrees  to 75 degrees  of knee flexion, and both ALB and PMB
      reconstructions are important for restraining PTT. At 90 degrees  of knee
      flexion, the ALB grafts may be more important to control PTT compared to PMB
      grafts; however, neither single-bundle reconstruction with ALB nor PMB could
      function as DB-PCLR did. In addition, PTT after DB-PCLR was strongly correlated
      side-to-side difference in posterior sag view at the final follow-up. The results
      from this study indicated that both ALB and PMB are important to stabilize PCL
      deficient knees. LEVEL OF EVIDENCE: Therapeutic study, Level III.

PMID- 25377194
TI  - RCVS starts testing an alternative system for resolving disputes.

PMID- 25377195
TI  - Badger Trust loses its legal appeal against the badger culls.

PMID- 25377196
TI  - Wales revises plans for bovine TB compensation payments.

PMID- 25377197
TI  - APHA guidance to help practitioners take samples for surveillance.

PMID- 25377198
TI  - Augmenting reality in anatomy.

PMID- 25377199
TI  - Vaccinology symposium celebrates a life in science.

PMID- 25377200
TI  - Joint venture group secures funding for long-term growth.

PMID- 25377202
TI  - Safety first: how running birds negotiate uneven terrain.

PMID- 25377204
TI  - Veterinary nursing: engaging with new roles and professionalism.

PMID- 25377201
TI  - Applying One Health to behaviour.
AB  - The British Veterinary Behaviour Association and the Association of Pet Behaviour
      Counsellors held a meeting last month to highlight the One Health principle with
      regard to the behaviour of people and animals, particularly pets. Caroline Bower
      reports. 

PMID- 25377205
TI  - Pathways to specialising in animal welfare.
AB  - Safeguarding animal welfare is an important aspect of the day-to-day work of
      almost all veterinarians; however, only some choose to pursue specific
      postgraduate qualifications in this area. Andrew Knight describes some of the
      routes to specialisation that are available around the world, highlighting in
      particular how suitably experienced individuals can currently seek accreditation
      in Europe and the USA without undertaking a formal programme of study.

PMID- 25377206
TI  - Vitamin D toxicity in sows.

PMID- 25377207
TI  - Feline hyperthyroidism: a common disorder with unknown pathogenesis.

PMID- 25377208
TI  - Bovine TB and badger control.

PMID- 25377209
TI  - Equine influenza vaccination certifications at riding events.

PMID- 25377210
TI  - Being a vet is so much more than working with animals.
AB  - Annika Little is a student at Glasgow vet school. Earlier this year she
      discovered that lambing is a fulfilling EMS experience; however, it was the
      family who welcomed her into their home that made her realise that being a vet is
      about working with people. 

PMID- 25377211
TI  - First-year student diary.
AB  - Now that her veterinary course is under way at Liverpool, Rosie Perrett has
      already begun learning fundamental clinical skills such as scrubbing up and
      bandaging. 

PMID- 25377212
TI  - Comments on non-utilising of rapid onsite evaluation with transbronchial needle
      aspiration.

PMID- 25377213
TI  - Validation of CT-MRI fusion for intraoperative assessment of stereotactic
      accuracy in DBS surgery.
AB  - Deep brain stimulation is typically performed with intraoperative microelectrode
      recording and test stimulation for target confirmation. Recent studies have shown
      accurate, clinically efficacious results after lead placement without
      microelectrode recording or test stimulation, using interventional magnetic
      resonance imaging (MRI) or intraoperative computed tomography (CT; iCT) for
      verification of accuracy. The latter relies on CT-MRI fusion. To validate CT-MRI
      fusion in this setting, we compared stereotactic coordinates determined
      intraoperatively using CT-MRI fusion with those obtained on postoperative MRI.
      Deep brain stimulation electrodes were implanted with patients under general
      anesthesia. Direct targeting was performed on preoperative MRI, which was merged
      with preimplantation iCT images for stereotactic registration and
      postimplantation iCT images for accuracy confirmation. Magnetic resonance imaging
      was obtained 6 weeks postoperatively for comparison. Postoperative MRI was
      obtained for 48 patients, with 94 leads placed over a 1-year period. Vector error
      of the targeted contact relative to the initial plan was 1.1 +/- 0.7 mm on iCT
      and 1.6 +/- 0.7 mm on postoperative MRI. Variance comparisons (F-tests) showed
      that the discrepancy between iCT- and postoperative MRI-determined errors was
      attributable to measurement error on postoperative MRI, as detected in inter
      rater reliability testing. In multivariate analysis, improved lead placement
      accuracy was associated with frame-based stereotaxy with the head of the bed at 0
      degrees  compared with frameless stereotaxy with the head of the bed at 30
      degrees  (P = 0.037). Intraoperative CT can be used to determine lead placement
      accuracy in deep brain stimulation surgery. The discrepancy between coordinates
      determined intraoperatively by CT-MRI fusion and postoperatively by MRI can be
      accounted for by inherent measurement error.

PMID- 25377214
TI  - The Effect of Mixed-Task Basic Training in the Acquisition of Advanced
      Laparoscopic Skills.
AB  - The aim of this study was to assess whether mixed practice of basic tasks on a
      virtual reality (VR) simulator improves the performance of advanced tasks on the
      same device used for training as well as on a video trainer (VT). Thirty-six
      novices were allocated into 3 equal groups. Each group practiced on different
      combinations of basic tasks on a VR simulator: (A) peg transfer, (B) peg transfer
      and clipping, and (C) peg transfer, clipping, and cutting. Before and after
      training, each group performed a laparoscopic cholecystectomy (LC) scenario on
      the simulator and intracorporeal knot tying (KT) on a VT. Assessment metrics
      included time, instrument's path length, penalty score, and hand motion
      synchronization. Results showed that for the common training tasks, plateau
      values were statistically equivalent for most assessment metrics (P > .05). For
      LC, all groups showed significant performance improvement (P < .05). For KT,
      group C improved significantly in pathlength (P < .005), penalty score (P < .05),
      and hand motion synchronization (P < .05); the other groups failed to show an
      improvement (P > .05). In conclusion, training on different VR tasks seems to
      have no effect on the performance of more demanding tasks on the same device.
      However, the number of different tasks practiced on the VR simulator seems to
      favorably affect the performance of advanced tasks on the VT. 

PMID- 25377215
TI  - Porcine Abdominal Wall Simulator for Laparotomy Incision and Closure.
AB  - We describe an economical and simple abdominal wall model that provides a
      realistic experience for trainees as they develop the skills of creating an
      abdominal incision through the midline, followed by closure of the fascia and
      skin. 

PMID- 25377216
TI  - A Comparative Study of Single-Port Laparoscopic Surgery Versus Robotic-Assisted
      Laparoscopic Surgery for Rectal Cancer.
AB  - INTRODUCTION: Conventional laparoscopic surgery is the treatment of choice for
      many abdominal procedures. To further reduce surgical trauma, new minimal
      invasive procedures such as single-port laparoscopic surgery (SPLS) and robotic
      assisted laparoscopic surgery (RALS) have emerged. The aim of this study was to
      compare the early results of SPLS versus RALS in the treatment of rectal cancer.
      METHODS: We performed a retrospective analysis of prospectively collected data on
      patients who had undergone SPLS (n = 36) or RALS (n = 56) in the period between
      2010 and 2012. Operative and short-term oncological outcomes were compared.
      RESULTS: The RALS group had fewer patients with low rectal cancer and more
      patients with mid-rectal tumors (P = .017) and also a higher rate of
      intraoperative complications (14.3% vs 0%, P = .021). The rate of postoperative
      complications did not differ (P = .62). There were no differences in
      circumferential resection margins, distal resection margins, or completeness of
      the mesorectal fascia. The RALS group had a larger number of median harvested
      lymph nodes (27 vs 13, P = .001). The SPLS group had fewer late complications (P
      = .025). There were no locoregional recurrences in either of the groups. There
      was no difference in median follow-up time between groups (P = .58). CONCLUSION:
      Both SPLS and RALS may have a role in rectal surgery. The short-term oncological
      outcomes were similar, although RALS harvested more lymph nodes than the SPLS
      procedure. However, SPLS seems to be safer with regard to intraoperative and late
      postoperative complications.

PMID- 25377217
TI  - Total synthesis of ascospiroketal a through a Ag(I) -promoted cyclization
      cascade.
AB  - The total synthesis of four candidate stereostructures for the marine octaketide
      ascospiroketal A have been achieved. These concise and highly stereocontrolled
      syntheses feature a unique Ag(I) -promoted cyclization cascade involving an
      oxetanyl ketochlorohydrin to access the entire tricyclic core of the natural
      product in one step. These syntheses also establish the full stereochemistry for
      the ascospiroketal natural products. 

PMID- 25377218
TI  - Applying micro-costing methods to estimate the costs of pharmacy interventions:
      an illustration using multi-professional clinical medication reviews in care
      homes for older people.
AB  - OBJECTIVES: Economic methods are underutilised within pharmacy research resulting
      in a lack of quality evidence to support funding decisions for pharmacy
      interventions. The aim of this study is to illustrate the methods of micro
      costing within the pharmacy context in order to raise awareness and use of this
      approach in pharmacy research. METHODS: Micro-costing methods are particularly
      useful where a new service or intervention is being evaluated and for which no
      previous estimates of the costs of providing the service exist. This paper
      describes the rationale for undertaking a micro-costing study before detailing
      and illustrating the process involved. The illustration relates to a recently
      completed trial of multi-professional medication reviews as an intervention
      provided in care homes. All costs are presented in UKL2012. KEY FINDINGS: In
      general, costing methods involve three broad steps (identification, measurement
      and valuation); when using micro-costing, closer attention to detail is required
      within all three stages of this process. The mean (standard deviation; 95%
      confidence interval (CI) ) cost per resident of the multi-professional medication
      review intervention was L104.80 (50.91; 98.72 to 109.45), such that the overall
      cost of providing the intervention to all intervention home residents was
      L36,221.29 (95% CI, 32 810.81 to 39 631.77). CONCLUSIONS: This study has
      demonstrated that micro-costing can be a useful method, not only for estimating
      the cost of a pharmacy intervention to feed into a pharmacy economic evaluation,
      but also as a source of information to help inform those designing pharmacy
      services about the potential time and costs involved in delivering such services.

PMID- 25377219
TI  - Eyelid closure in embryogenesis is required for ocular adnexa development.
AB  - PURPOSE: Mammalian eye development requires temporary fusion of the upper and
      lower eyelids in embryogenesis. Failure of lid closure in mice leads to an eye
      open at birth (EOB) phenotype. Many genetic mutant strains develop this phenotype
      and studies of the mutants lead to a better understanding of the signaling
      mechanisms of morphogenesis. The present study investigates the roles of lid
      closure in eye development. METHODS: Seven mutant mouse strains were generated by
      different gene ablation strategies that inactivated distinct signaling pathways.
      These mice, including systemic ablation of Map3k1 and Dkk2, ocular surface
      epithelium (OSE) knockout of c-Jun and Egfr, conditional knockout of Shp2 in
      stratified epithelium (SE), as well as the Map3k1/Jnk1 and Map3k1/Rhoa compound
      mutants, all exhibited defective eyelid closure. The embryonic and postnatal eyes
      in these mice were characterized by histology and immunohistochemistry. RESULTS:
      Some eye abnormalities, such as smaller lens in the Map3k1-null mice and
      Harderian gland hypoplasia in the Dkk2-null mice, appeared to be mutant strain
      specific, whereas other abnormalities were seen in all mutants examined. The
      common defects included corneal erosion/ulceration, meibomian gland hypoplasia,
      truncation of the eyelid tarsal muscles, failure of levator palpebrae superioris
      (LPS) extension into the upper eyelid and misplacement of the inferior oblique
      (IO) muscle and inferior rectus (IR) muscle. The muscle defects were traced to
      the prenatal fetuses. CONCLUSIONS: In addition to providing a protective barrier
      for the ocular surface, eyelid closure in embryogenesis is required for the
      development of ocular adnexa, including eyelid and extraocular muscles.

PMID- 25377220
TI  - Endothelial nitric oxide synthase-related mechanotransduction changes in aged
      porcine angular aqueous plexus cells.
AB  - PURPOSE: To investigate effects of aging on endothelial nitric oxide synthase
      (eNOS) expression and signaling in angular aqueous plexus (AAP) (functional
      equivalent to human Schlemm's canal) cells subjected to shear stress. METHODS:
      The AAP cells were isolated differentially from porcine outflow tissues using
      puromycin selection. Cell aging was induced by culturing cells in hyperoxia
      condition (40% oxygen and 5% carbon dioxide) for 14 days. The AAP cells grown in
      chamber slides were exposed to a shear stress of 8 dynes/cm(2) for 24 hours.
      Expression of eNOS, eNOS-phospho Thr495, eNOS-phospho Ser1177, and Akt-phospho
      was tested by Western blot analysis and immunofluorescence staining. Nitric oxide
      (NO) levels were measured using the Griess assay. RESULTS: Compared with control,
      eNOS levels in aged cells were significantly reduced by 60% (P < 0.05; n = 6).
      Phosphorylation of eNOS at Ser1177 and Akt at Ser473 was 63% and 80% lower in
      aged cells, respectively, whereas phosphorylation of the eNOS inhibition site
      (Thr495) increased by 6.1-fold (P < 0.05; n = 6). Shear stress (8 dynes/cm(2) for
      24 hours) increased eNOS abundance (total protein and at cell borders) and
      phosphorylation at Ser1177 by 1.7-fold and 1.8-fold, respectively (P < 0.05; n =
      6), whereas aged cells were unresponsive. In control cells exposed to shear
      stress, the NO concentration was 1.8-fold higher than in the static group (P <
      0.05; n = 4); however, aged cells were unresponsive to shear stress (mean +/- SD,
      4.3 +/- 1.3 vs. 4.1 +/- 1.4 MUM). CONCLUSIONS: Aged AAP cells appear compromised
      in their mechanotransduction machinery involving eNOS, the protein product of the
      gene, NOS3, polymorphisms of which impart a risk for the development of glaucoma.

PMID- 25377221
TI  - Design and characterization of an ocular topical liposomal preparation to
      replenish the lipids of the tear film.
AB  - PURPOSE: Dry eye (DE) includes a group of diseases related to tear film
      disorders. Current trends for DE therapy focus on providing lipid components to
      replace the damaged lipid layer. Formulations that contain aqueous and mucin-like
      compounds may have additional therapeutic benefits for DE patients. The aim of
      this work was to design and evaluate novel formulations having the potential to
      become topical treatment for DE. METHODS: Unpreserved liposomal formulations
      composed of phosphatidylcholine (PC), cholesterol, and alpha-tocopherol (vit E)
      were prepared by the thin-film hydration technique. Formulations were
      characterized in terms of liposome size, pH, surface tension, osmolarity, and
      viscosity. In vitro tolerance assays were performed on macrophage, human corneal,
      and conjunctival cell lines at short- and long-term exposures. In vivo ocular
      tolerance was studied after instillation of the formulation. RESULTS: The mean
      liposome size was less than 1 MUm and surface tension < 30 mN/m for all
      formulations. The final liposomal formulation (PC-cholesterol-vit E in a ratio of
      8:1:0.8) had physiological values of pH (6.45 +/- 0.09), osmolarity (289.43 +/-
      3.28 mOsm), and viscosity (1.82 +/- 0.02 mPa . s). Cell viability was greater
      than 80% in the corneal and conjunctival cells. This formulation was well
      tolerated by experimental animals. CONCLUSIONS: The unpreserved liposomal
      formulation has suitable properties to be administered by a topical ophthalmic
      route. The liposome-based artificial tear had good in vitro and in vivo tolerance
      responses. This formulation, composed of a combination of liposomes and
      bioadhesive polymers, may be used successfully as a tear film substitute in DE
      therapy.

PMID- 25377222
TI  - Damage to the immature optic radiation causes severe reduction of the retinal
      nerve fiber layer, resulting in predictable visual field defects.
AB  - PURPOSE: The aim of the present study was to seek evidence of a relationship
      between damage to the optic radiation (OR) in the immature brain and subsequent
      development of the retinal nerve fiber layer (RNFL) and associated visual
      manifestations. METHODS: Seven cases (2 males and 5 females ranging in age from
      18 to 35 years old) were selected from a large cohort of individuals with known
      white matter damage of immaturity (WMDI), who had presented with visual
      dysfunction. They underwent magnetic resonance imaging (MRI), including diffusion
      weighted MRI. Visual function was evaluated by best-corrected visual acuity and
      visual field (VF) testing using Goldmann perimetry and Humphrey field analyzer
      (HFA). RNFL thickness was measured by optical coherence tomography. RESULTS: A
      homogeneous lesion pattern with bilateral WMDI predominantly in the superior
      posterior periventricular white matter was seen in all subjects. However, as
      shown by white matter fiber tractography, only cases with injuries to the
      superior portion of the OR had corresponding inferior VF defects. In the
      individuals showing structural abnormalities in the OR, a commensurate reduction
      in the peripapillary RNFL was seen. The RNFL loss was most pronounced in the
      subjects suffering from the more extensive lesions, and it followed the pattern
      of OR damage in the sense that damage in the superior portion of the OR gave a
      reduced RNFL thickness in the superior part of the peripapillary RNFL.
      CONCLUSIONS: Primary injuries in the immature OR are associated with reduced RNFL
      thickness, and examination of the RNFL may be a helpful predictor of VF defects.

PMID- 25377224
TI  - Models of glaucomatous visual field loss.
AB  - PURPOSE: To evaluate and compare the ability of pointwise linear, exponential,
      and logistic functions, and combinations of functions, to model the longitudinal
      behavior of visual field (VF) series and predict future VF loss in patients with
      glaucoma. METHODS: Visual field series from 782 eyes (572 patients) with open
      angle glaucoma had greater than 6 years of follow-up and 12 VFs performed.
      Threshold sensitivities from the first 5 years at each location were regressed
      with linear, exponential, and logistic functions to estimate model parameters. A
      multiple-model approach applied the model with the lowest root mean square error
      (RMSE) at each location as the preferred model for future predictions.
      Predictions for each model were compared at 1, 2, 3, and 5 years after the last
      VF used to determine model parameters. RESULTS: There were no clinically
      important differences between any of the models tested for fit; however, the
      logistic function had the lowest average RMSE (P < 0.001). For predictions, the
      exponential model consistently had the lowest average prediction RMSE for all
      time intervals (P < 0.001); the multiple-model approach did not perform better
      than the exponential model (P < 0.001). CONCLUSIONS: While the logistic model
      best fit glaucomatous VF behavior over a long time period, the exponential model
      provided the best average predictions. A multiple-model approach for VF
      predictions was associated with a greater prediction error than with the best
      performing single-model approach. A model's goodness of fit is not indicative of
      its predictive ability for measurements of glaucomatous VFs.

PMID- 25377223
TI  - A hypoxia-responsive glial cell-specific gene therapy vector for targeting
      retinal neovascularization.
AB  - PURPOSE: Muller cells, the major glial cell in the retina, play a significant
      role in retinal neovascularization in response to tissue hypoxia. We previously
      designed and tested a vector using a hypoxia-responsive domain and a glial
      fibrillary acidic protein (GFAP) promoter to drive green fluorescent protein
      (GFP) expression in Muller cells in the murine model of oxygen-induced
      retinopathy (OIR). This study compares the efficacy of regulated and unregulated
      Muller cell delivery of endostatin in preventing neovascularization in the OIR
      model. METHODS: Endostatin cDNA was cloned into plasmids with hypoxia-regulated
      GFAP or unregulated GFAP promoters, and packaged into self-complementary adeno
      associated virus serotype 2 vectors (scAAV2). Before placement in hyperoxia on
      postnatal day (P)7, mice were given intravitreal injections of regulated or
      unregulated scAAV2, capsid, or PBS. Five days after return to room air, on P17,
      neovascular and avascular areas, as well as expression of the transgene and
      vascular endothelial growth factor (VEGF), were compared in OIR animals treated
      with a vector, capsid, or PBS. RESULTS: The hypoxia-regulated, glial-specific,
      vector-expressing endostatin reduced neovascularization by 93% and reduced the
      central vaso-obliteration area by 90%, matching the results with the unregulated
      GFAP-Endo vector. Retinas treated with the regulated endostatin vector expressed
      substantial amounts of endostatin protein, and significantly reduced VEGF
      protein. Endostatin production from the regulated vector was undetectable in
      retinas with undamaged vasculature. CONCLUSIONS: These findings suggest that the
      hypoxia-regulated, glial cell-specific vector expressing endostatin may be useful
      for treatment of neovascularization in proliferative diabetic retinopathy.

PMID- 25377226
TI  - Laser speckle and hydrogen gas clearance measurements of optic nerve circulation
      in albino and pigmented rabbits with or without optic disc atrophy.
AB  - PURPOSE: The purpose of this study was to evaluate the correlation between laser
      speckle flowgraphy measurements of mean blur rate (MBR) and hydrogen gas
      clearance measurements of capillary blood flow (CBF) in the optic nerve head
      (ONH) of albino and pigmented rabbits, with or without chronic ischemia-induced
      ONH atrophy. METHODS: The ONH MBR and ONH CBF were measured at baseline, 30 and
      60 minutes after the intravenous administration of endothelin-1 (ET-1) (10(-10)
      mol/kg) in six albino and six pigmented rabbit eyes. The ONH MBR and ONH CBF were
      also measured in nine pigmented rabbit eyes that underwent the intravitreal
      administration of ET-1 (20 pmol) twice per week for 4 weeks to provoke chronic
      ischemia-induced ONH atrophy. RESULTS: In the group that received intravenous ET
      1, average measurements of ONH MBR and ONH CBF at all time points were correlated
      in both the albino (r = 0.88, P < 0.001, n = 18) and pigmented rabbits (r = 0.85,
      P < 0.001, n = 18), with no intrarabbit correlations (P = 0.524). The ONH MBR and
      ONH CBF were also correlated in the model of chronic ischemia-induced ONH atrophy
      (r = 0.78, P = 0.013, n = 9). Pooled ONH MBR and ONH CBF measurements in both the
      intravenous and intravitreal groups were also highly correlated (r = 0.87, P <
      0.001, n = 45), with no significant intergroup differences in the relationship
      between ONH MBR and ONH CBF (P = 0.138). CONCLUSIONS: Regardless of the presence
      of fundus pigmentation or ONH atrophy, ONH MBR and ONH CBF were highly
      correlated, suggesting that MBR in the ONH tissue is usable for interindividual
      and intergroup comparisons.

PMID- 25377225
TI  - Transcriptome analysis of the human corneal endothelium.
AB  - PURPOSE: To comprehensively characterize human corneal endothelial cell (HCEnC)
      gene expression and age-dependent differential gene expression and to identify
      expressed genes mapped to chromosomal loci associated with the corneal
      endothelial dystrophies posterior polymorphous corneal dystrophy (PPCD)1, Fuchs
      endothelial corneal dystrophy (FECD)4, and X-linked endothelial dystrophy (XECD).
      METHODS: Total RNA was isolated from ex vivo corneal endothelium obtained from
      six pediatric and five adult donor corneas. Complementary DNA was hybridized to
      the Affymetrix GeneChip 1.1ST array. Data analysis was performed using Partek
      Genomics Suite software, and differentially expressed genes were validated by
      digital molecular barcoding technology. RESULTS: Transcripts corresponding to
      12,596 genes were identified in HCEnC. Nine genes displayed the most significant
      differential expression between pediatric and adult HCEnC: CAPN6, HIST1H3A,
      HIST1H4E, and HSPA2 were expressed at higher levels in pediatric HCEnC, while
      ITGBL1, NALCN, PREX2, TAC1, and TMOD1 were expressed at higher levels in adult
      HCEnC. Analysis of the PPCD1, FECD4 and XECD loci demonstrated transcription of
      53/95 protein-coding genes in the PPCD1 locus, 27/40 in the FECD4 locus, and
      35/68 in the XECD locus. CONCLUSIONS: An analysis of the HCEnC transcriptome
      reveals the expression of almost 13,000 genes, with less than 1% mapped to
      chromosomal loci associated with PPCD1, FECD4, and XECD. At least nine genes
      demonstrated significant differential expression between pediatric and adult
      HCEnC, defining specific functional properties distinct to each age group. These
      data will serve as a resource for vision scientists investigating HCEnC gene
      expression and can be used to focus the search for the genetic basis of the
      corneal endothelial dystrophies for which the genetic basis remains unknown.

PMID- 25377227
TI  - Importance of fasting in preparing dogs for abdominal ultrasound examination of
      specific organs.
AB  - OBJECTIVE: To describe the effect of fasting on the technical success of
      abdominal ultrasonography specifically in respect of examination of the gall
      bladder, duodenum, pancreas, adrenal glands and portal vein in dogs. METHODS:
      Randomised, prospective study of 150 dogs with a variety of physical
      characteristics. Animals were divided into two groups of 75 dogs each. Dogs in
      Group 1 were fasted for 8 to 12 hours before ultrasonographic evaluation and
      those in Group 2 were not but received food anytime between 10 minutes and 2
      hours before the procedure. RESULTS: Intraluminal gas can influence the
      visibility of organs, but intraluminal gas accumulation occurred independently of
      fasting status. The assessment of abdominal organs was not affected by whether or
      not an animal was fasted. CLINICAL SIGNIFICANCE: Routine fasting of dogs before
      abdominal ultrasonography is not essential.

PMID- 25377228
TI  - [Self-management support for patients with chronic obstructive pulmonary disease
      in ambulatory care--an observational study].
AB  - This cross-sectional study focuses on the status of COPD-related fears and
      impairments of adult patients receiving ambulant care as well as their use of
      self-management strategies. On the basis of the COPD Clinical Questionnaire, COPD
      Disability Index, COPD Assessment Test and the COPD Anxiety Questionnaire, COPD
      dependent fears and impairments were determined in a convenience sample.
      Furthermore, data on important characteristics of the illness experience were
      gathered by semi-standardised interviews. Altogether, 80 patients (average age:
      67.1 +/- 8.5 years) took part in the quantitative interviews. In addition, 10
      patients (average age: 68.2 +/- 4.1 years) took part in qualitative interviews.
      Results showed that there were disease-related impairments in the areas of
      respiration, recovery and physical stress as well as in family and domestic
      obligations. Furthermore, illness-dependent fears had a high relevance in the
      study population. The management of COPD-related fears and taking into
      consideration information and counseling needs of these patients are important
      intervention approaches. On the basis of the presented results, evidence-based,
      multi-disciplinary, and disease-, situation- and above all, patient' needs
      related interventions could be planned to support patients in self-management
      skills.

PMID- 25377229
TI  - [Infiltration of the superior vena cava in NSCLC: results of surgical
      intervention].
AB  - The benefits of surgical therapy of locally advanced non-small cell lung cancer
      (NSCLC) with infiltration of the superior vena cava (SVC) remains controversial.
      Here we describe our therapeutic approach and results of our intervention.A
      retrospective analysis of 22 patients with NSCLC who underwent SVC replacement (n
      = 17) or reconstruction (n = 5) between 1998 and 2013 was performed.
      Pneumonectomy was necessary in 16 patients, lobectomy in 8. Preoperative
      chemotherapy was administered to 3 patients, 16 received postoperative radiation
      treatment. The clinical course and survival were analyzed.Major postoperative
      morbidities were found in 13 patients. Graft thrombosis did not occur. Thirty-day
      mortality was 7 % in pneumonectomy patients and 0 % following lobectomy. Local
      recurrence was found in 4.5 %, distant metastases developed in 54.5 % of the
      patients (p = 0.0008). One- and five-year survival probabilities for all patients
      were 63.6 and 27.9 %. Five-year survival probability was 33 % for patients with
      SVC reconstruction and 25 % for patients with SVC replacement (p = 0.22). Five
      year survival rates after pneumonectomy and lobectomy were 21.4 % and 37.5 %,
      respectively (p = 0.18).Radical resection involving the SVC in carefully selected
      patients with NSCLC results in excellent local tumor control. Due to the high
      rate of distant metastases, application of induction and adjuvant chemotherapy
      should be carefully assessed.

PMID- 25377230
TI  - Mineralocorticoid and SGK1-sensitive inflammation and tissue fibrosis.
AB  - Effects of mineralocorticoids are not restricted to regulation of epithelial salt
      transport, extracellular volume and blood pressure; mineralocorticoids also
      influence a wide variety of seemingly unrelated functions such as inflammation
      and fibrosis. The present brief review addresses the role of mineralocorticoids
      in the orchestration of these latter processes. Mineralocorticoids foster
      inflammation as well as vascular, cardiac, renal and peritoneal fibrosis.
      Mechanisms involved in mineralocorticoid-sensitive inflammation and fibrosis
      include the serum- and glucocorticoid-inducible kinase 1 (SGK1), which is
      genomically upregulated by mineralocorticoids and transforming growth factor beta
      (TGF-beta), and stimulated by mineralocorticoid-sensitive phosphatidylinositide 3
      kinase. SGK1 upregulates the inflammatory transcription factor nuclear factor
      kappaB, which in turn stimulates the expression of diverse inflammatory mediators
      including connective tissue growth factor. Moreover, SGK1 inhibits the
      degradation of the TGF-beta-dependent transcription factors Smad2/3.
      Mineralocorticoids foster the development of TH17 cells, which is compromised
      following SGK1 deletion. Excessive SGK1 expression is observed in a wide variety
      of fibrosing diseases including lung fibrosis, diabetic nephropathy,
      glomerulonephritis, obstructive kidney disease, experimental nephrotic syndrome,
      obstructive nephropathy, liver cirrhosis, fibrosing pancreatitis, peritoneal
      fibrosis, Crohn's disease and celiac disease. The untoward inflammatory and
      fibrosing effects of mineralocorticoids could be blunted or even reversed by
      mineralocorticoid receptor blockers, which may thus be considered in the
      treatment of inflammatory and/or fibrosing disease.

PMID- 25377231
TI  - Transurethral resection of the prostate in recurrent acute bacterial prostatitis.
AB  - OBJECTIVE: To explore the outcome of transurethral resection of the prostate
      (TURP) in the treatment of refractory recurrent acute bacterial prostatitis.
      PATIENTS AND METHODS: From 2004 to 2013, 23 TURP for this indication were
      performed in 21 patients; two patients underwent it twice. The files of these
      patients were retrospectively analysed for outcome and side effects. TURP
      intended to remove as much infected tissue as possible under appropriate
      antibiotherapy. RESULTS: Twelve patients became free of symptoms during a follow
      up of 3-108 months (median 44), two others became disease-free after one and two
      postoperative attacks, respectively; eight were not cured and had rapid
      recurrences; three patients had follow-up of a few weeks only. Two failures
      developed orchiepididymitis shortly after the procedure and one a year later. No
      incontinence or bladder neck contracture was noted. CONCLUSION: TURP is an
      acceptable procedure in the treatment of refractory recurrent bacterial
      prostatitis. It could cure about two thirds of patients.

PMID- 25377232
TI  - Transesophageal echocardiography in thoracic anesthesia: pulmonary hypertension
      and right ventricular function.
AB  - PURPOSE OF REVIEW: Pulmonary hypertension is associated with increased
      postoperative morbidity and mortality. Early diagnosis and echocardiographic
      detection of right ventricular (RV) dysfunction are paramount in perioperative
      management. The goal of this review is to provide an overview of the recent
      literature on this topic. RECENT FINDINGS: Doppler interrogation of pulmonary
      artery flow may provide an insight into the severity and mechanism of pulmonary
      hypertension. Established echocardiographic techniques of RV assessment have
      multiple limitations. Newer echocardiographic technologies (strain and three
      dimensional imaging) are promising, but require further validation in the
      perioperative setting before they are adopted. SUMMARY: More pulmonary
      hypertension patients are presenting for noncardiac surgery, creating a challenge
      for the anesthesiologist. Echocardiographic detection of RV dysfunction can be
      difficult. Routine use of intraoperative transesophageal echocardiography in
      major thoracic surgery is not advocated yet, but the development of automated
      techniques may provide an objective assessment of RV function.

PMID- 25377233
TI  - Gender and sex manifestations in hysteria across medicine and the arts.
AB  - The diagnosis of hysteria has existed for at least four-thousand years, with
      roots in the ancient Greek word hysterikos, referring to diseases of the womb. In
      the sixteenth-century medical discourses, female hysteria was caused by excess
      pollution of the womb, with fluids that were labelled 'female sperm' as the
      probable cause. In the work of Shakespeare, there is a reference to hysterica
      passio, a term used by King Lear to self-diagnose his affliction. Shakespeare
      shows how a disease associated with women, and the 'wandering womb' phenomenon
      could have been spoken of in an associative way. At this time, there is a
      transformation of the nature of hysteria from a neurological consequence of the
      sick womb, to sexual deviance. Portrayals of the male deviant would evolve by the
      Victorian era, concurrent with the diagnosis of 'spermatorrhea'. There are very
      direct correspondences between the hysteria of spermatorrhea and the notion in
      Western medicine of the direct links between female hysteria and too much or not
      enough sexual energy release. Hysteria in both sexes was famously diagnosed and
      catalogued by Jean-Martin Charcot at the end of the nineteenth century. By the
      twentieth century, hysteria was also depicted as a disorder of gender as well as
      sexuality.

PMID- 25377235
TI  - Does the primary site of colorectal cancer impact outcomes for patients with
      metastatic disease?
AB  - BACKGROUND: Previous reports have described differences in biology and outcome
      for colorectal cancer based on whether the primary is right or left sided.
      Further division by right, left, and rectum or even exact primary site has also
      been explored. Possible differences in response to biological agents have also
      been reported based on side of primary lesion. METHODS: We explored the South
      Australian registry for metastatic colorectal cancer to assess if there were any
      differences in patient characteristics, prognostic markers, and treatment
      received and outcomes based on whether the primary was right or left sided. We
      also explored if differences exist based on left colon and rectum and by exact
      primary site. RESULTS: Two thousand nine hundred seventy-two patients were
      analyzed. Thirty-five percent had a right-sided primary. The median overall
      survival for the entire group right versus left was 9.6 versus 20.3 months (P <
      .001). Multivariate analysis confirmed side of primary as an independent
      prognostic factor. For the group that had active therapy, defined as chemotherapy
      (+/- metastasis resection), median overall survival was right, 18.2 months; and
      left, 29.4 months (P < .001). Importantly, we found no suggestion of major
      differences if left side was divided by left colon and rectum, and trends by
      individual site still supported a left and right division. CONCLUSIONS: Patients
      with a right-sided primary have more negative prognostic factors and indeed have
      inferior outcomes compared with those with a left-sided primary. Our data with
      further breakdown by exact site still favor a simple left-versus-right division
      moving forward for metastatic colorectal cancer.

PMID- 25377236
TI  - A critical review and meta-analysis of the perceptual pseudoneglect across
      psychiatric disorders: is there a continuum?
AB  - The phenomenon known as "perceptual pseudoneglect" refers to the leftward bias in
      visuospatial attention in non-clinical samples, possibly as a consequence of
      right hemisphere dominance for visuospatial attention. The degree of such a
      lateralized visuospatial attention bias is often assessed using the line
      bisection task. Interestingly, various psychiatric disorders may influence the
      expression of this phenomenon. The aim of this paper was to perform a critical
      appraisal of the literature on the expression of the perceptual pseudoneglect
      across all psychiatric disorders accompanied by meta-analytical evaluation of the
      data. Moreover, we will discuss whether this phenomenon may be considered as a
      trait marker across different psychiatric disorders. 

PMID- 25377238
TI  - Spin-orbital dynamics in a system of polar molecules.
AB  - Spin-orbit coupling in solids normally originates from the electron motion in the
      electric field of the crystal. It is key to understanding a variety of spin
      transport and topological phenomena, such as Majorana fermions and recently
      discovered topological insulators. Implementing and controlling spin-orbit
      coupling is thus highly desirable and could open untapped opportunities for the
      exploration of unique quantum physics. Here we show that dipole-dipole
      interactions can produce an effective spin-orbit coupling in two-dimensional
      ultracold polar molecule gases. This spin-orbit coupling generates chiral
      excitations with a non-trivial Berry phase 2pi. These excitations, which we call
      chirons, resemble low-energy quasiparticles in bilayer graphene and emerge
      regardless of the quantum statistics and for arbitrary ratios of kinetic to
      interaction energies. Chirons manifest themselves in the dynamics of the spin
      density profile, spin currents and spin coherences, even for molecules pinned in
      a deep optical lattice and should be observable in current experiments. 

PMID- 25377237
TI  - Human rhinovirus C infections in pediatric hematology and oncology patients.
AB  - Children with cancer and HSCT recipients are at high risk for common viral
      infections. We sought to define the viral etiology of ARI and identify risk
      factors. Nasal wash samples were collected from pediatric hematology-oncology
      patients and HSCT recipients with ARI during the 2003-2005 winter seasons. Real
      time RT-PCR was performed to detect Flu A, influenza B, RSV, PIV 1-3, human MPV,
      and HRV. HRV specimens were sequenced and genotyped. Seventy-eight samples from
      62 children were included. Viruses were detected in 31 of 78 samples (40%). HRV
      were detected most frequently, in 16 (52%) including five HRVC; followed by seven
      (22%) RSV, five (16%) Flu A, four (13%) MPV, and two (6%) PIV2. There was a trend
      toward higher risk of viral infection for children in day care. Only 8% of the
      study children had received influenza vaccine. HRV, including the recently
      discovered HRVC, are an important cause of infection in pediatric oncology and
      HSCT patients. Molecular testing is superior to conventional methods and should
      be standard of care, as HRV are not detected by conventional methods. 

PMID- 25377239
TI  - Evidence for genes controlling resistance to Heligmosomoides bakeri on mouse
      chromosome 1.
AB  - Resistance to infections with Heligmosomoides bakeri is associated with a
      significant quantitative trait locus (QTL-Hbnr1) on mouse chromosome 1 (MMU1). We
      exploited recombinant mice, with a segment of MMU1 from susceptible C57Bl/10 mice
      introgressed onto MMU1 in intermediate responder NOD mice (strains 1094 and
      6109). BALB/c (intermediate responder) and C57Bl/6 mice (poor responder) were
      included as control strains and strain 1098 (B10 alleles on MMU3) as NOD
      controls. BALB/c mice resisted infection rapidly and C57Bl/6 accumulated heavy
      worm burdens. Fecal egg counts dropped by weeks 10-11 in strain 1098, but strains
      1094 and 6109 continued to produce eggs, harbouring more worms when autopsied
      (day 77). PubMed search identified 3 genes (Ctla4, Cd28, Icos) as associated with
      'Heligmosomoides' in the B10 insert. Single nucleotide polymorphism (SNP)
      differences in Ctla4 could be responsible for regulatory changes in gene
      function, and a SNP within a splice site in Cd28 could have an impact on
      function, but no polymorphisms with predicted effects on function were found in
      Icos. Therefore, one or more genes encoded in the B10 insert into NOD mice
      contribute to the response phenotype, narrowing down the search for genes
      underlying the H. bakeri resistance QTL, and suggest Cd28 and Ctla4 as candidate
      genes. 

PMID- 25377240
TI  - Bridging the data gaps in the epidemiology of hepatitis C virus infection in
      Malaysia using multi-parameter evidence synthesis.
AB  - BACKGROUND: Collecting adequate information on key epidemiological indicators is
      a prerequisite to informing a public health response to reduce the impact of
      hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute
      data shortage typical of low/middle income countries using statistical modelling
      to estimate the national HCV prevalence and the distribution over transmission
      pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis
      methods were applied to combine all available relevant data sources - both direct
      and indirect - that inform the epidemiological parameters of interest. RESULTS:
      An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV
      antibody-positive individuals were living in Malaysia in 2009; this represents
      2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay
      ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was
      active or a previous history of injecting drugs. The corresponding proportions
      were smaller for male Chinese and Indian/other ethnic groups (40% and 71%,
      respectively). The estimated prevalence in females of all ethnicities was 1% (95%
      CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to
      non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of
      persons living with HCV infection in Malaysia is estimated to be very high.
      Low/middle income countries often lack a comprehensive evidence base; however,
      evidence synthesis methods can assist in filling the data gaps required for the
      development of effective policy to address the future public health and economic
      burden due to HCV.

PMID- 25377241
TI  - Executive impairment predicts schizophrenia diagnosis and treatment status in mid
      term follow-up of early-onset psychosis.
AB  - OBJECTIVES: Early-onset psychoses (EOP) vary considerably with regard to
      diagnostic stability and functional outcome. The aim of this study was the
      assessment of executive dysfunction as a predictor of outcome in EOP. METHOD:
      This was a retrospective cohort study. Twenty-five hospitalized patients with non
      affective EOP were assessed with the Wisconsin Card Sorting Test (WCST) during
      the index admission. Associations with current diagnosis, further admissions,
      current treatment status and occupational and relationship outcome were analyzed
      in 6 years of follow-up. RESULTS: The mean age at the index admission and the
      follow-up was 16.1 +/- 1.35 and 22.0 +/- 2.1 years, respectively. After
      discharge, almost all subjects (96%) at least briefly continued psychiatric
      treatment, and the majority of them (76%) were readmitted. Worse baseline WCST
      results were associated with a follow-up schizophrenia diagnosis, being a
      psychiatric in- or outpatient at the moment of follow-up assessment and receiving
      psychotropic medication. A low number of completed categories correlated with
      receiving a disability pension at the follow-up. CONCLUSION: In patients with
      EOP, baseline executive function impairment was associated with schizophrenia
      diagnosis and psychiatric treatment at the follow-up. The association between
      baseline results and psychiatric treatment may explain the limited effect of
      baseline impairment on follow-up occupational and relationship status.

PMID- 25377242
TI  - Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral
      direct factor Xa inhibitor.
AB  - AIM: Apixaban is an orally active inhibitor of coagulation factor Xa and is
      eliminated by multiple pathways, including renal and non-renal elimination. Non
      renal elimination pathways consist of metabolism by cytochrome P450 (CYP)
      enzymes, primarily CYP3A4, as well as direct intestinal excretion. Two single
      sequence studies evaluated the effect of ketoconazole (a strong dual inhibitor of
      CYP3A4 and P-glycoprotein [P-gp]) and diltiazem (a moderate CYP3A4 inhibitor and
      a P-gp inhibitor) on apixaban pharmacokinetics in healthy subjects. METHOD: In
      the ketoconazole study, 18 subjects received apixaban 10 mg on days 1 and 7, and
      ketoconazole 400 mg once daily on days 4-9. In the diltiazem study, 18 subjects
      received apixaban 10 mg on days 1 and 11 and diltiazem 360 mg once daily on days
      4-13. RESULTS: Apixaban maximum plasma concentration and area under the plasma
      concentration-time curve extrapolated to infinity increased by 62% (90%
      confidence interval [CI], 47, 78%) and 99% (90% CI, 81, 118%), respectively, with
      co-administration of ketoconazole, and by 31% (90% CI, 16, 49%) and 40% (90% CI,
      23, 59%), respectively, with diltiazem. CONCLUSION: A 2-fold and 1.4-fold
      increase in apixaban exposure was observed with co-administration of ketoconazole
      and diltiazem, respectively.

PMID- 25377243
TI  - Examining the quality of name code record linkage: what is the impact on death
      and cancer risk estimates? A validation study.
AB  - OBJECTIVE: To examine the validity and impact of record linkage using name code
      compared to full name records. METHODS: A registry of 45,419 opioid substitution
      clients (1985-2007) was linked with national population-based death and cancer
      registries using registrant's name, date of birth, sex, state, postcode and date
      of death. Records were linked using full name and then using the first two
      letters of the given and surname (2*2 name code). Sensitivity and specificity
      were computed and regression analysis used to identify factors related to linkage
      accuracy. Standardised mortality ratios (SMR) and standardised cancer incidence
      ratios (SIR) were estimated. RESULTS: The sensitivity and specificity of name
      code compared to full name linkage were 65.31% and 99.91% for death records and
      76.81% and 99.89% for cancer records. Registrants' age and sex and accuracy of
      the registries were associated with risk of false linkages. Death and cancer
      risks (SMR 6.98, 95%CI 6.77-7.19; SIR 1.16, 95%CI 1.08-1.24) were significantly
      under-estimated using name code linkage (SMR 4.39, 95%CI 4.23-4.56; SIR 0.92,
      95%CI 0.85-0.99). CONCLUSION: Record linkage using 2*2 name code has low
      sensitivity but high specificity, resulting in conservative estimates of death
      and cancer risk. This may translate to meaningful differences in outcomes.

PMID- 25377244
TI  - The impact of systematic errors on gestational age estimation.

PMID- 25377245
TI  - Accuracy of resting energy expenditure calculations in unselected overweight and
      obese patients.
AB  - AIMS: Measurements of resting energy expenditure (REE) were compared with the
      data of 14 equations to determine their accuracy. METHODS: REE measurements by
      indirect calorimetry in 1,032 unselected overweight and obese men (n = 306) and
      women (n = 726) were compared with calculations by 14 different formulas.
      RESULTS: The mean (+/- SD) values calculated with the Owen, Robertson and Reid
      and WHO-I equations were not significantly different from our measurement of
      1,682 +/- 441.9 kcal/24 h. The values obtained with the Livingston, Mifflin,
      Muller and Bernstein equations were significantly different but still within a
      range of +/-100 kcal/24 h. For females, the best comparison was observed with the
      Muller equation which, however, differed substantially in males. For men, the
      Cunningham equation was best, but it gave the worst comparison in women. A good
      individual match was only obtained with the equation of Robertson and Reid in 34%
      of the men and with the Owen equation in 38% of the women. All other formulas
      were less accurate. Drug treatment for 55% of the subjects had no effect on the
      mismatch between calculated and measured data. CONCLUSION: Calculations of REE
      with most equations seem to be valid in a group analysis but they are not helpful
      for the estimation of an obese patient's individual energy expenditure.

PMID- 25377247
TI  - pH-stimulated DNA hydrogels exhibiting shape-memory properties.
AB  - Nucleic acid-functionalized polyacrylamide chains that are cooperatively cross
      linked by i-motif and nucleic acid duplex units yield, at pH 5.0, DNA hydrogels
      exhibiting shape-memory properties. Separation of the i-motif units at pH 8.0
      dissolves the hydrogel into a quasi-liquid phase. The residual duplex units
      provide, however, a memory code in the quasi-liquid allowing the regeneration of
      the hydrogel shape at pH 5.0. 

PMID- 25377246
TI  - Pharmacokinetic analysis of the FAK scaffold inhibitor C4 in dogs.
AB  - Inhibition of focal adhesion kinase-vascular endothelial growth factor receptor 3
      complex by C4 was previously shown to reduce tumor growth alone and
      synergistically with other chemotherapeutic agents in animal tumor models. Single
      and multiple dose IV and oral dosing studies were performed in dogs to determine
      C4 pharmacokinetics. C4 was administered to 4 dogs at 1.25 or 2.50 mg/kg IV, or
      7.50 mg/kg oral gavage. Single- (IV and oral) and multiple- (IV) dose
      pharmacokinetic samples were collected on days 1 and 3 at pre-dose and 0.5, 1, 2,
      4, 8, 24, 120, 144, and 168 h post-dose. C4 concentrations were determined using
      liquid chromatography with tandem mass spectral detection with a limit of
      quantitation of 2.50 pg/mL. Pharmacokinetics of C4 was characterized by a 3
      compartment model with linear distributional and elimination clearances using
      Phoenix 64 WinNonlin 6.3. Mean C4 plasma concentration-time profiles revealed a
      triexponential decline following either IV or oral administration, independent of
      dose with no accumulation. For the 2.5 mg/kg dose, the median half-life was ~21
      h. Median C max and area under the curve (AUC0-24) were similar for days 1 and 3.
      Oral bioavailability for formulations of PBS, TPGS, Maalox((r)), and Pepcid((r))
      was greatest with TPGS (45 %), followed by Maalox((r)) (42 %), Pepcid((r)) (37
      %), and PBS (30 %). The pharmacokinetic study revealed that C4 has linear
      pharmacokinetics and does not accumulate following multiple-dose administration.
      Characterization of C4 pharmacokinetics provides a better understanding of the
      novel targeted agent, which will help facilitate further development of C4. 

PMID- 25377248
TI  - Screening and identification of a cutinase-producing Rhodotorula mucilaginosa and
      properties of the cutinase.
AB  - Eucommia leaf contains large amounts of natural active products. In extracting
      the substances, the most important is the removal of the cuticle layer on the
      leaves and the cell wall in the leaves of Eucommia ulmoides. But the removal of
      the cuticle layer is a technical difficulty now. Cutinase (EC3.1.1.74) is a
      multifunctional enzyme with a common alpha/beta fold structure belonging to
      hydroplane that can make a substantial degradation of horny fatty acids. So this
      study isolated bacteria capable of producing cutinase from the lesion of Eucommia
      leaves and identified the bacteria. The identification using PCR-RFLP method
      confirmed that the strain belongs to Rhodotorula mucilaginosa. The fermentation
      conditions of the strain-producing cutinase were optimized in this study. The
      finding of cutinase-producing R. mucilaginosa is significant because the yeast is
      more secure than plant pathogens, being suitable for mass production.

PMID- 25377249
TI  - The dipeptide H-Trp-Arg-OH (WR) Is a PPARalpha agonist and reduces hepatic lipid
      accumulation in lipid-loaded H4IIE cells.
AB  - Dipeptides absorbed by the intestinal epithelium are delivered to circulation,
      but their metabolic roles are not yet clearly understood. We investigated the
      biological activities of a dietary dipeptide, H-Trp-Arg-OH (WR), on the
      regulation of peroxisome proliferator-activated receptor (PPAR) alpha activity.
      Reporter gene assays revealed that WR dose-dependently induced PPARalpha
      transactivation. Surface plasmon resonance experiments demonstrated that WR
      interacts directly with the PPARalpha ligand binding domain, and time-resolved
      fluorescence energy transfer analyses revealed recruitment of a co-activator
      peptide, fluorescein-PGC1alpha, to PPARalpha, confirming the direct binding of WR
      to PPARalpha and occurrence of conformational changes. WR induced cellular fatty
      acid uptake and the expression of PPARalpha response genes in fatty acid
      oxidation, thus reducing intracellular triglyceride accumulation in lipid-loaded
      hepatocytes. In conclusion, the dietary dipeptide WR activates PPARalpha and
      reduces hepatic lipid accumulation in lipid-loaded hepatocytes.

PMID- 25377250
TI  - Pyrolysis oil-based lipid production as biodiesel feedstock by Rhodococcus
      opacus.
AB  - Light oil from pyrolysis, which accounts for ~10 % carbon yield of the starting
      biomass, is a complex aqueous product that is difficult to utilize and usually
      discarded. This work presents the feasibility of light oil as a sole carbon
      source to support the growth of Rhodococcus opacus (R. opacus) that in turn
      accumulate triacylglycerols as biodiesel feedstock. Two types of bacteria (R.
      opacus PD630 and DSM 1069) were selected in this study. Research results showed
      that after short adaption periods both strains can grow well on this complex
      carbon source, as proved by the consumption of oligomers and monomers in light
      oil. Lipid content by R. opacus PD630 and DSM 1069 was observed up to 25.8 % and
      22.0 % of cell dry weight, respectively. Palmitic and stearic acids were found to
      be the predominant fatty acids in these bacterial cells. In addition, the light
      oil-based lipid production can be enhanced by reducing the pH value from 7 to 4,
      especially in case of DSM 1069.

PMID- 25377251
TI  - Overexpression of Rcan1-1L inhibits hypoxia-induced cell apoptosis through
      induction of mitophagy.
AB  - Mitophagy, a cellular process that selectively targets dysfunctional mitochondria
      for degradation, is currently a hot topic in research into the pathogenesis and
      treatment of many human diseases. Considering that hypoxia causes mitochondrial
      dysfunction, which results in cell death, we speculated that selective activation
      of mitophagy might promote cell survival under hypoxic conditions. In the present
      study, we introduced the Regulator of calcineurin 1-1L (Rcan1-1L) to initiate the
      mitophagy pathway and aimed to evaluate the effect of Rcan1-1L-induced mitophagy
      on cell survival under hypoxic conditions. Recombinant adenovirus vectors
      carrying Rcan1-1L were transfected into human umbilical vein endothelial cells
      and human adult cardiac myocytes. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide MTT assay and Trypan blue exclusion assay, Rcan1-1L
      overexpression was found to markedly reverse cell growth inhibition induced by
      hypoxia. Additionally, Rcan1-1L overexpression inhibited cell apoptosis under
      hypoxic conditions, as detected by annexin V-fluorescein isothiocyanate
      (FITC)/propidium iodide (PI) apoptosis assay. Meanwhile, the mitochondria
      mediated cell apoptotic pathway was inhibited by Rcan1-1L. In contrast, knockdown
      of Rcan1-1L accelerated hypoxia-induced cell apoptosis. Moreover, Rcan1-1L
      overexpression significantly reduced mitochondrial mass, decreased depolarized
      mitochondria, and downregulated ATP and reactive oxygen species production. We
      further delineated that the loss of mitochondrial mass was due to the activation
      of mitophagy induced by Rcan1-1L. Rcan1-1L overexpression activated autophagy
      flux and promoted translocation of the specific mitophagy receptor Parkin into
      mitochondria from the cytosol, whereas inhibition of autophagy flux resulted in
      the accumulation of Parkin-loaded mitochondria. Finally, we demonstrated that
      mitochondrial permeability transition pore opening was significantly increased by
      Rcan1-1L overexpression, which suggested that Rcan1-1L might evoke mitophagy
      through regulating mitochondrial permeability transition pores. Taken together,
      we provide evidence that Rcan1-1L overexpression induces mitophagy, which in turn
      contributes to cell survival under hypoxic conditions, revealing for the first
      time that Rcan1-1L-induced mitophagy may be used for cardioprotection. 

PMID- 25377252
TI  - Lessons from yeast on emerging roles of the ATAD2 protein family in gene
      regulation and genome organization.
AB  - ATAD2, a remarkably conserved, yet poorly characterized factor is found
      upregulated and associated with poor prognosis in a variety of independent
      cancers in human. Studies conducted on the yeast Saccharomyces cerevisiae ATAD2
      homologue, Yta7, are now indicating that the members of this family may primarily
      be regulators of chromatin dynamics and that their action on gene expression
      could only be one facet of their general activity. In this review, we present an
      overview of the literature on Yta7 and discuss the possibility of translating
      these findings into other organisms to further define the involvement of ATAD2
      and other members of its family in regulating chromatin structure and function
      both in normal and pathological situations. 

PMID- 25377253
TI  - Antagonistic regulation of Arabidopsis growth by brassinosteroids and abiotic
      stresses.
AB  - To withstand ever-changing environmental stresses, plants are equipped with
      phytohormone-mediated stress resistance mechanisms. Salt stress triggers abscisic
      acid (ABA) signaling, which enhances stress tolerance at the expense of growth.
      ABA is thought to inhibit the action of growth-promoting hormones, including
      brassinosteroids (BRs). However, the regulatory mechanisms that coordinate ABA
      and BR activity remain to be discovered. We noticed that ABA-treated seedlings
      exhibited small, round leaves and short roots, a phenotype that is characteristic
      of the BR signaling mutant, brassinosteroid insensitive1-9 (bri1-9). To identify
      genes that are antagonistically regulated by ABA and BRs, we examined published
      Arabidopsis microarray data sets. Of the list of genes identified, those
      upregulated by ABA but downregulated by BRs were enriched with a BRRE motif in
      their promoter sequences. After validating the microarray data using quantitative
      RT-PCR, we focused on RD26, which is induced by salt stress. Histochemical
      analysis of transgenic Arabidopsis plants expressing RD26pro:GUS revealed that
      the induction of GUS expression after NaCl treatment was suppressed by co
      treatment with BRs, but enhanced by co-treatment with propiconazole, a BR
      biosynthetic inhibitor. Similarly, treatment with bikinin, an inhibitor of BIN2
      kinase, not only inhibited RD26 expression, but also reduced the survival rate of
      the plant following exposure to salt stress. Our results suggest that ABA and BRs
      act antagonistically on their target genes at or after the BIN2 step in BR
      signaling pathways, and suggest a mechanism by which plants fine-tune their
      growth, particularly when stress responses and growth compete for resources. 

PMID- 25377254
TI  - Gene expression profiling in osteoclast precursors by insulin using microarray
      analysis.
AB  - The balance between bone formation by osteoblasts and destruction of mineralized
      bone matrix by osteoclasts is important for bone homeostasis. The increase of
      osteoclast differentiation by RANKL induces bone diseases such as osteoporosis.
      Recent studies have shown that insulin is one of main factors mediating the cross
      talk between bone remodeling and energy metabolism. However, the systemic
      examination of insulin-induced differential gene expression profiles in
      osteoclasts has not been extensively studied. Here, we investigated the global
      effects of insulin on osteoclast precursors at the level of gene transcription by
      microarray analysis. The number of genes that were up-regulated by >= 1.5 fold
      after insulin treatment for 6 h, 12 h, or 24 h was 76, 73, and 39; and 96, 83,
      and 54 genes were down-regulated, respectively. The genes were classified by 20
      biological processes or 24 molecular functions and the number of genes involved
      in 'development processes' and 'cell proliferation and differentiation' was 25
      and 18, respectively, including Inhba, Socs, Plk3, Tnfsf4, and Plk1. The
      microarray results of these genes were verified by real-time RT-PCR analysis. We
      also compared the effects of insulin and RANKL on the expression of these genes.
      Most genes had a very similar pattern of expressions in insulin- and RANKL
      treated cells. Interestingly, Tnfsf4 and Inhba genes were affected by insulin but
      not by RANKL. Taken together, these results suggest a potential role for insulin
      in osteoclast biology, thus contributing to the understanding of the pathogenesis
      and development of therapeutics for numerous bone and metabolic diseases. 

PMID- 25377255
TI  - The role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells.
AB  - This study was to investigate the mechanism and role of Kif4A in doxorubicin
      induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF
      7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the
      expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP
      ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and
      examined the apoptosis by flow cytometry after treatment with doxorubicin and
      PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin
      treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down
      regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of
      PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment
      in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only
      slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further
      demonstrated that overexpression of Kif4A could reduce the level of PAR and
      significantly increase apoptosis. The effect of doxorubicin on apoptosis was more
      profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken
      together, our results suggest that the novel role of Kif4A in doxorubicin-induced
      apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP
      1. 

PMID- 25377256
TI  - Bone marrow cellular cannibalism by medulloblastoma.

PMID- 25377258
TI  - Root surface strain during canal shaping and its influence on apical microcrack
      development: a preliminary investigation.
AB  - AIM: To determine the root surface strain (RSS) generated during root canal
      shaping and its effects on apical microcrack development. METHODOLOGY: Twenty
      five extracted human mandibular premolars were selected and decoronated. The
      teeth were instrumented with either the ProTaper (PT) or WaveOne (WO) (Dentsply
      Maillefer) NiTi rotary systems (n = 10 per group) or used as controls (n = 5).
      Instrumented root canals were enlarged to ProTaper F4 (size 40, 0.06 taper) or
      using WaveOne LARGE (size 40, 0.08 taper) instruments according to the
      manufacturer's instructions. An electrical strain gage (KFG02-120-C1-16, Kyowa
      Dengyo, Tokyo, Japan) was fixed on the proximal root surface and connected to a
      strain amplifier via a bridge box in order to measure RSS. During canal shaping,
      the strain output of the amplifier was recorded. The instantaneous RSS induced by
      each instrument and the maximum RSSs were determined. All teeth were then stained
      with contrast media and imaged with micro-computed tomography (micro-CT) at an
      isotropic resolution of 10 MUm to detect microcracks. The mean maximum RSS values
      (microstrain) and mean number of microcracks recorded for both groups were tested
      for statistical significance using Mann-Whitney U-test. Presence/absence of
      microcracks in both groups was compared by chi-square tests. RESULTS: Increased
      baseline RSS from strain accumulation during canal shaping was observed, with
      similar maximum RSS (mean +/- SD) for PT (416.6 +/- 185.1 MUstrain) and WO (398.2
      +/- 163.8 MUstrain) (P = 0.94). The interevaluator reliability for microcrack
      detection using micro-CT had a kappa value of 0.998. Compared to the PT group,
      there was a trend for fewer samples with microcracks in the WO group (P = 0.051).
      On the micro-CT images, apical microcracks were detected in 20 PT and 11 WO
      samples (P = 0.10). The microcracks were observed in the buccolingual direction
      in all WO and 81% of PT samples. No vertical root fractures were found. The
      maximum RSS obtained during canal shaping was poorly correlated with the number
      of microcracks found (R(2)  = 0.093). CONCLUSIONS: Based on these preliminary
      data, canal shaping appears to cause apical microcracks regardless of the type of
      rotary instrument motion. Contrast-enhanced micro-CT was able to identify
      microcracks in roots.

PMID- 25377257
TI  - BactPepDB: a database of predicted peptides from a exhaustive survey of complete
      prokaryote genomes.
AB  - With the recent progress in complete genome sequencing, mining the increasing
      amount of genomic information available should in theory provide the means to
      discover new classes of peptides. However, annotation pipelines often do not
      consider small reading frames likely to be expressed. BactPepDB, available online
      at http://bactpepdb.rpbs.univ-paris-diderot.fr, is a database that aims at
      providing an exhaustive re-annotation of all complete prokaryotic genomes
      chromosomal and plasmid DNA-available in RefSeq for coding sequences ranging
      between 10 and 80 amino acids. The identified peptides are classified as (i)
      previously identified in RefSeq, (ii) entity-overlapping (intragenic) or
      intergenic, and (iii) potential pseudogenes-intergenic sequences corresponding to
      a portion of a previously annotated larger gene. Additional information is
      related to homologs within order, predicted signal sequence, transmembrane
      segments, disulfide bonds, secondary structure, and the existence of a related 3D
      structure in the Protein Databank. As a result, BactPepDB provides insights about
      candidate peptides, and provides information about their conservation, together
      with some of their expected biological/structural features. The BactPepDB
      interface allows to search for candidate peptides in the database, or to search
      for peptides similar to a query, according to the multiple properties predicted
      or related to genomic localization. Database URL: http://www.yeastgenome.org/ 

PMID- 25377260
TI  - Theoretical insights into nucleation of CO2 and CH4 hydrates for CO2 capture and
      storage.
AB  - We present a hybrid three-dimensional (3D) theoretical approach, the density
      functional theory (DFT) integrated with the reference interaction site model
      (RISM), to investigate the nucleation of CO2 and CH4 hydrates. Within the
      theoretical framework, the 3D-RISM is applied to describe gas density
      distributions in hydrate cages, and the 3D-DFT is used to describe the
      interfacial structure and properties of the two hydrates, as well as their
      nucleation. The crystal-liquid phase equilibria of CO2 and CH4 hydrates are
      predicted by the hybrid 3D-DFT-RISM, and compared with the available experimental
      data to examine the theoretical model. In particular, the local and interfacial
      structure and properties, the critical nucleus radii and free-energy barriers at
      moderate concentration supersaturation are presented to analyze their nucleation.
      The formation enthalpies for the two hydrates are calculated to evaluate the
      possibility of CO2 storage by CH4-CO2 replacement in hydrate. 

PMID- 25377259
TI  - A sensitive assay of mercury using fluorescence correlation spectroscopy of gold
      nanoparticles.
AB  - We described a new and sensitive method for the determination of mercury ions
      (Hg(2+) ) on the basis of fluorescence correlation spectroscopy (FCS) and
      recognition of oligonucleotides. In this assay, 30-nm gold nanoparticles (GNPs)
      were modified with oligonucleotides containing thymine bases (T) as fluorescent
      probes, and the principle of this assay was based on the specific binding of
      Hg(2+) by two DNA thymine bases. When two GNPs labelled with different
      oligonucleotides were mixed with a sample containing Hg(2+), the T-Hg(2+)-T
      binding reaction should cause GNPs to form dimers (or oligomers), which would
      lead to a significant increase in the characteristic diffusion time of GNPs in
      the detection volume. The FCS method is a single molecule detection method and
      can sensitively detect the change in the characteristic diffusion time of GNPs
      before and after binding reactions. The quantitative analysis was performed
      according to the relation between the change in the characteristic diffusion time
      of GNPs and the concentration of Hg(2+). Under optimal conditions, the linear
      range of this method was from 0.3 nM to 100 nM, and the detection limit was 0.14
      nM for Hg(2+). This new method was successfully applied for direct determination
      of Hg(2+) levels in water and cosmetics samples.

PMID- 25377261
TI  - Controlled Zn-mediated grafting of thin layers of bipodal diazonium salt on gold
      and carbon substrates.
AB  - A controlled, rapid, and potentiostat-free method has been developed for grafting
      the diazonium salt (3,5-bis(4-diazophenoxy)benzoic acid tetrafluoroborate
      (DCOOH)) on gold and carbon substrates, based on a Zn-mediated chemical
      dediazonation. The highly stable thin layer organic platforms obtained were
      characterized by cyclic voltammetry, AFM, impedance, XP, and Raman
      spectroscopies. A dediazonation mechanism based on radical formation is proposed.
      Finally, DCOOH was proved as a linker to an aminated electroactive probe. 

PMID- 25377263
TI  - Phenolic contents and antioxidant activity of ethanolic extract of Capparis
      spinosa.
AB  - Caper plant (Capparis spinosa) extracts have been associated with diverse
      biological activities including anti-oxidant properties. In this work, we
      characterized the hydro-ethanolic extract obtained from C. spinosa leaves
      [hydroethanolic extract of C. spinosa (HECS)] by analyzing the content in anti
      oxidant compounds such as polyphenols, flavonoids and anthocyanins. Further, we
      evaluated HECS antioxidant activities in vitro using bleaching of 1,1-diphenyl-2
      picrylhydrazyl radical and ABTS test as well as by pretreatment of HeLa cells
      exposed to Fe(2+) or H2O2. Our findings indicate that HECS contains high amount
      of total phenolic compounds and high levels of flavonoids and anthocyanins.
      Furthermore, HECS exhibited antioxidant activity in both chemical and biological
      tests. Specially, pretreatment of HeLa cells with different concentrations of the
      extract conferred protection against lipid peroxidation and modulated activities
      of two antioxidant enzymes, SOD and catalase. These results revealed HECS
      antioxidant effects and suggest that C. spinosa leaves are a potential source of
      natural antioxidant molecules with possible applications in industry and
      medicine. 

PMID- 25377262
TI  - Ionic alpha-helical polypeptides toward nonviral gene delivery.
AB  - The advent of polymeric materials has significantly promoted the development and
      rapid growth of various technologies in biomedical applications, such as tissue
      engineering and controlled drug and gene delivery. Water-soluble polypeptides
      bearing functional side chains and adopting stable secondary structures are a new
      class of functional polymeric materials of potentially broad applications in
      medicine and biotechnology. In this article, we summarize our recent effort on
      the design and synthesis of the water-soluble alpha-helical ionic polypeptides
      originally developed in our laboratory and highlight their applications in cell
      membrane penetration and nonviral gene/small interfering RNA (siRNA) delivery.

PMID- 25377265
TI  - What is more informative in the history of science, the signal or the noise?

PMID- 25377264
TI  - Fetal heart extract facilitates the differentiation of human umbilical cord blood
      derived mesenchymal stem cells into heart muscle precursor cells.
AB  - Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are a
      promising stem cell source with the potential to modulate the immune system as
      well as the capacity to differentiate into osteoblasts, chondrocytes, and
      adipocytes. In previous publications, UCB-MSCs have been successfully
      differentiated into cardiomyocytes. This study aimed to improve the efficacy of
      differentiation of UCB-MSCs into cardiomyocytes by combining 5-azacytidine (Aza)
      with mouse fetal heart extract (HE) in the induction medium. UCB-MSCs were
      isolated from umbilical cord blood according to a published protocol. Murine
      fetal hearts were used to produce fetal HE using a rapid freeze-thaw procedure.
      MSCs at the 3rd to 5th passage were differentiated into cardiomyocytes in two
      kinds of induction medium: complete culture medium plus Aza (Aza group) and
      complete culture medium plus Aza and fetal HE (Aza + HE group). The results
      showed that the cells in both kinds of induction medium exhibited the phenotype
      of cardiomyocytes. At the transcriptional level, the cells expressed a number of
      cardiac muscle-specific genes such as Nkx2.5, Gata 4, Mef2c, HCN2, hBNP, alpha
      Ca, cTnT, Desmin, and beta-MHC on day 27 in the Aza group and on day 18 in the
      Aza + HE group. At the translational level, sarcomic alpha-actin was expressed on
      day 27 in the Aza group and day 18 in the Aza + HE group. Although they expressed
      specific genes and proteins of cardiac muscle cells, the induced cells in both
      groups did not contract and beat spontaneously. These properties are similar to
      properties of heart muscle precursor cells in vivo. These results demonstrated
      that the fetal HE facilitates the differentiation process of human UCB-MSCs into
      heart muscle precursor cells. 

PMID- 25377266
TI  - Phylogenetic Relationships and Morphological Character Evolution of
      Photosynthetic Euglenids (Excavata) Inferred from Taxon-rich Analyses of Five
      Genes.
AB  - Photosynthetic euglenids acquired chloroplasts by secondary endosymbiosis, which
      resulted in changes to their mode of nutrition and affected the evolution of
      their morphological characters. Mapping morphological characters onto a reliable
      molecular tree could elucidate major trends of those changes. We analyzed
      nucleotide sequence data from regions of three nuclear-encoded genes (nSSU, nLSU,
      hsp90), one chloroplast-encoded gene (cpSSU) and one nuclear-encoded chloroplast
      gene (psbO) to estimate phylogenetic relationships among 59 photosynthetic
      euglenid species. Our results were consistent with previous works; most genera
      were monophyletic, except for the polyphyletic genus Euglena, and the
      paraphyletic genus Phacus. We also analyzed character evolution in photosynthetic
      euglenids using our phylogenetic tree and eight morphological traits commonly
      used for generic and species diagnoses, including: characters corresponding to
      well-defined clades, apomorphies like presence of lorica and mucilaginous stalks,
      and homoplastic characters like rigid cells and presence of large paramylon
      grains. This research indicated that pyrenoids were lost twice during the
      evolution of phototrophic euglenids, and that mucocysts, which only occur in the
      genus Euglena, evolved independently at least twice. In contrast, the evolution
      of cell shape and chloroplast morphology was difficult to elucidate, and could
      not be unambiguously reconstructed in our analyses.

PMID- 25377267
TI  - An open-source automated platform for three-dimensional visualization of subdural
      electrodes using CT-MRI coregistration.
AB  - OBJECTIVE: Visualizing implanted subdural electrodes in three-dimensional (3D)
      space can greatly aid in planning, executing, and validating resection in
      epilepsy surgery. Coregistration software is available, but cost, complexity,
      insufficient accuracy, or validation limit adoption. We present a fully automated
      open-source application, based on a novel method using postimplant computerized
      tomography (CT) and postimplant magnetic resonance (MR) images, for accurately
      visualizing intracranial electrodes in 3D space. METHODS: CT-MR rigid brain
      coregistration, MR nonrigid registration, and prior-based segmentation were
      carried out on seven patients. Postimplant CT, postimplant MR, and an external
      labeled atlas were then aligned in the same space. The coregistration algorithm
      was validated by manually marking identical anatomic landmarks on the postimplant
      CT and postimplant MR images. Following coregistration, distances between the
      center of the landmark masks on the postimplant MR and the coregistered CT images
      were calculated for all subjects. Algorithms were implemented in open-source
      software and translated into a "drag and drop" desktop application for Apple Mac
      OS X. RESULTS: Despite postoperative brain deformation, the method was able to
      automatically align intrasubject multimodal images and segment cortical
      subregions, so that all electrodes could be visualized on the parcellated brain.
      Manual marking of anatomic landmarks validated the coregistration algorithm with
      a mean misalignment distance of 2.87 mm (standard deviation 0.58 mm)between the
      landmarks. Software was easily used by operators without prior image processing
      experience. SIGNIFICANCE: We demonstrate an easy to use, novel platform for
      accurately visualizing subdural electrodes in 3D space on a parcellated brain. We
      rigorously validated this method using quantitative measures. The method is
      unique because it involves no preprocessing, is fully automated, and freely
      available worldwide. A desktop application, as well as the source code, are both
      available for download on the International Epilepsy Electrophysiology Portal
      (https://www.ieeg.org) for use and interactive refinement.

PMID- 25377268
TI  - Correlation of rectal tumor volumes with oncological outcomes for low rectal
      cancers: does tumor size matter?
AB  - PURPOSES: Several reports have described a relationship between tumor volume and
      oncological outcomes for certain cancers. There is paucity of similar data for
      rectal cancer. We conducted this study to establish whether tumor volume,
      mesorectal volume, and the tumor volume to mesorectal volume ratio (TV/MRV),
      evaluated by magnetic resonance imaging (MRI), affect the oncological outcomes of
      patients with rectal cancer. METHODS: We performed volumetric analysis of rectal
      tumors from magnetic resonance imaging (MRI) images and assessed their
      correlation with oncological outcomes, using clinical and radiological databases.
      RESULTS: The subjects of this study were 25 of 35 patients who underwent rectal
      cancer surgery after staging with MRI, after the exclusion of 7 patients for whom
      MRI images could not be retrieved and 3 patients who had metastases identified at
      diagnosis. Tumor volume (TV) was a significant predictor of overall survival
      hazard ratio (95% CI); 5.8 (1.2-29), (P = 0.03). Mesorectal volume (MRV) and
      TV/MRV did not correlate with oncological outcomes. CONCLUSIONS: We found a
      direct relationship between tumor volume and overall survival, which may be used
      to stratify rectal tumors for neoadjuvant therapy. A larger prospective study is
      required to confirm this correlation.

PMID- 25377269
TI  - Effects of ghrelin administration on the early postoperative inflammatory
      response after esophagectomy.
AB  - PURPOSE: Ghrelin is a unique gastric hormone, which has pleiotropic biological
      functions, including anti-inflammatory effects. The aim of this study was to
      investigate the effects of administering ghrelin on reducing postoperative
      systemic inflammation in patients undergoing esophagectomy. METHODS: The safety
      and effectiveness of postoperative ghrelin administration were investigated among
      twenty esophageal cancer patients who underwent esophagectomy between May 2010
      and August 2011. Two different regimens of ghrelin administration, twice daily
      rapid drip infusion (3 MUg/kg, twice a day) or continuous infusion (0.5
      MUg/kg/h), were employed. The duration of the systemic inflammatory response
      syndrome (SIRS) and the hematological parameters were compared between groups.
      RESULTS: Patients treated with ghrelin showed shorter SIRS durations than
      controls (1.6 +/- 2.7 vs. 4.1 +/- 3.7 days, respectively; p = 0.0065) and also
      showed lower C-reactive protein concentrations than controls (11.0 +/- 4.6 mg/dL
      vs. 15.3 +/- 7.3 mg/mL, respectively, on postoperative day 3, p = 0.030). Ghrelin
      administration was not associated with any adverse events. The incidence of
      operative morbidity was equivalent between groups. The two ghrelin administration
      regimens showed similar durations of systemic inflammatory response (rapid drip:
      2.2 +/- 3.3 vs. continuous: 1.1 +/- 1.9 days, p = 0.17). CONCLUSIONS:
      Postoperative ghrelin administration is safe and may suppress protracted
      postoperative inflammation in patients who undergo esophagectomies.

PMID- 25377270
TI  - Diagnosis of metachronous multiple lung adenocarcinoma at the cut-end by
      epidermal growth factor receptor mutation status discordance 4 years after
      sublobar resection for adenocarcinoma in situ: report of a case.
AB  - We report a case of metachronous multiple lung adenocarcinoma at the cut-end,
      diagnosed 4 years after sublobar resection for adenocarcinoma in situ (AIS), on
      the basis of discordance of epidermal growth factor receptor (EGFR) mutation
      status between the first and second tumor. The patient was an 81-year-old
      Japanese man, whose chest computer tomography (CT) scan showed mixed ground-glass
      opacity in the right upper lobe of the lung. Wedge resection was performed and a
      diagnosis of AIS, non-mucinous (18 * 14 mm), with a margin of 6 mm, was made. A
      tumor at the cut-end was seen on a CT scan 4 years later, and abnormal uptake was
      identified by fluorine-18 fluorodeoxyglucose-positron emission tomography. Right
      upper lobectomy and lymph node dissection were performed and the tumor was
      diagnosed as invasive adenocarcinoma, acinar predominant. Discordance of EGFR
      mutation status between the first tumor, harboring exon 19 deletion, and the
      second tumor, having an L858R point mutation in exon 21, revealed that the second
      tumor was metachronous multiple lung cancer. This case demonstrates the necessity
      of comparing EGFR mutation status between the first tumor and the second tumor at
      the cut-end.

PMID- 25377271
TI  - Tenax extraction of sediments to estimate desorption and bioavailability of
      hydrophobic contaminants: a literature review.
AB  - Characterizing sediment-associated hydrophobic contaminants is problematic,
      because assessing the total amount of a compound available for chemical exchange
      with an organism is difficult. To address this, contaminant concentrations have
      been normalized for specific sediment characteristics (including organic C
      content) or the chemical activity has been estimated using passive samplers.
      Another approach to assess compound availability is to determine the extent of
      readily desorbed compound using resin extractions of sediment slurries. The
      present paper reviews the literature that uses Tenax(r) TA, a 2,6-diphenylene
      oxide polymer as an extraction tool to measure bioavailability of hydrophobic
      organic contaminants in sediment. Some work has assessed the extent of desorption
      with sequential extractions to characterize the maximum rate and pool sizes for
      different desorbing fractions of bound contaminant. As such, the rapidly
      desorbing fraction has been well correlated with the extent of degradation,
      bioaccumulation, and toxicity of hydrophobic contaminants. A shortcut to
      measuring the full desorption curve to determine the rapidly desorbing compound
      is to use a single-point extraction, with 6  h or 24  h extractions being the
      most common. The Tenax extraction has been shown to be effective with laboratory
      spiked sediments, field-collected sediments, laboratory-exposed organisms, field
      collected organisms, and studies among laboratories. Furthermore, a literature
      based model has described the bioaccumulation of polychlorinated biphenyls from
      independently measured field-collected sediments. Despite the success of this
      approach, applying the Tenax method to manage contaminated sediments is limited
      by the absence of a standard set of conditions to perform the extractions, as
      well as standard methods for using field sediments.

PMID- 25377272
TI  - Belatacept treatment for two yr after liver transplantation is not associated
      with operational tolerance.
AB  - Belatacept was recently evaluated in liver transplantation (LT) in a phase II
      multicenter trial, which was terminated prematurely. Patients were more than two
      yr post-LT at the time. As high rates of spontaneous tolerance after LT have been
      reported and as belatacept has marked immunomodulatory effects, we decided to
      maintain the belatacept patients enrolled at our center (n = 4) on MMF
      monotherapy. All belatacept patients on MMF monotherapy developed graft
      dysfunction consistent with acute rejection after a mean period of 10.3 (7-14)
      wk. Patients were therefore switched to triple therapy with CNI, MMF, and
      corticosteroids. Graft dysfunction resolved within 1-3 wk after switch. At the
      time of belatacept discontinuation, mean eGFR was 105.1 mL/min/1.73 m2 (92.1
      118.9) in belatacept patients compared to 58 mL/min/1.73 m2 (36.1-98.2) in
      controls (p = 0.022). One yr after the switch to CNI therapy, eGFR had declined
      by 27.4 mL (19.2-39.3; p = 0.008). Thus, LT patients treated with belatacept show
      superior kidney function that declines upon institution of CNIs. MMF monotherapy
      following withdrawal of belatacept is associated with a high incidence of graft
      dysfunction. Belatacept has no obvious immunomodulatory effects in LT recipients
      that would be sufficient to allow drug withdrawal with a high rate of success. 

PMID- 25377273
TI  - Managing the challenge of PTLD in liver and bowel transplant recipients.
AB  - Post-transplant lymphoproliferative disorder (PTLD) remains a common complication
      of liver and bowel transplantion. The ubiquity of Epstein-Barr virus (EBV)
      combined with engraftment of organs rich with lymphatic tissue and the
      requirement of highly immunosuppressive regimens are factors that account for the
      high frequency and poor prognosis of PTLD in this population. Early detection of
      the virus followed by pre-emptive reduction of immunosuppression are essential
      components in the management of PTLD, but can increase the risk of graft loss.
      More recently, the anti-CD20 monoclonal antibody (rituximab) has been shown to
      improve survival in various transplant populations with PTLD, while other
      therapeutic options, such as chemotherapy, surgery or radiotherapy, have minimal
      clinical impact. EBV-directed cytotoxic T cells have shown promise in the
      management of PTLD but clinical use is currently limited by lack of technical
      facilities worldwide. 

PMID- 25377274
TI  - The impact of drug use patterns on mortality among polysubstance users in a
      Canadian setting: a prospective cohort study.
AB  - BACKGROUND: Illicit drug use is a well-established risk factor for morbidity and
      mortality. However, few studies have examined the impact of different drug use
      patterns on mortality among polysubstance using populations. This study aimed to
      identify drug-specific patterns of mortality among a cohort of polysubstance
      using persons who inject drugs (PWIDs). METHODS: PWIDs in Vancouver, Canada were
      prospectively followed between May 1996 and December 2011. Participants were
      linked to the provincial vital statistics database to ascertain mortality rates
      and causes of death. We used multivariate Cox proportional hazards regression to
      investigate the relationships between drug use patterns (daily alcohol use,
      heroin injection and non-injection use, cocaine injection, amphetamine injection
      and non-injection use, crack smoking and speedball injecting) and time to all
      cause mortality. RESULTS: 2330 individuals were followed for a median of 61
      months (inter-quartile range: 33 - 112). In total, 466 (19.1%) individuals died
      for an incidence density of 3.1 (95% confidence interval [CI]: 2.8 - 3.4) deaths
      per 100 person-years. In multivariate analyses, after adjusting for HIV infection
      and other potential confounders, only daily cocaine injection remained
      independently associated with all-cause mortality (adjusted hazard ratio [AHR] =
      1.36, 95% CI: 1.06 - 1.76). CONCLUSIONS: Although heroin injecting is
      traditionally viewed as carrying the highest risk of mortality, in this setting,
      only daily cocaine injecting was associated with all-cause mortality. These
      findings highlight the urgent need to identify novel treatments and harm
      reduction strategies for cocaine injectors.

PMID- 25377275
TI  - NIH grant awards as a metric of clinical and translational research training
      effectiveness.
AB  - The number of clinical research training programs has increased over the past 5
      10 years, but few studies have quantitatively evaluated the effectiveness of
      these programs. The goal of this study was to evaluate the clinical and
      translational research training program at the University of Cincinnati by
      comparing the number of National Institutes of Health grants awarded to pediatric
      fellows who graduated from the MS degree program between 1995 and 2013 versus
      fellows who did not pursue an MS degree. Among 394 pediatric fellows, 16 of 81
      (20%) MS alumni were awarded at least one NIH grant, as compared with 28 of 313
      (9%) fellows who did not obtain an MS degree (p < 0.02). In multivariable
      analysis, MS alumni were more than three times as likely to have received at
      least one grant than were non-MS fellows (OR = 3.5, 95% CI [1.7-7.2]; C-statistic
      = 0.71) and MS alumni were more likely to obtain at least one K-series (OR = 4.1,
      95% CI [1.6-10.2]; C-statistic = 0.74), M-series (OR = 11.8, 95% CI [3.4-41.4]; C
      statistic = 0.81), or R-series (OR = 10.1, 95% CI [2.4-42.8]; C-statistic = 0.74)
      grant than were non-MS fellows. These findings suggest that graduate training in
      clinical and translational research prepares graduates for the highly competitive
      field of clinical and translational research. 

PMID- 25377276
TI  - Development of second-generation small-molecule RhoA inhibitors with enhanced
      water solubility, tissue potency, and significant in vivo efficacy.
AB  - RhoA, a member of the Rho GTPases, is involved in a variety of cellular functions
      and could be a suitable therapeutic target for the treatment of cardiovascular
      diseases. However, few small-molecule RhoA inhibitors have been reported. Based
      on our previously reported lead compounds, 32 new 2-substituted quinoline (or
      quinoxaline) derivatives were synthesized and tested in biological assays. Six
      compounds showed high RhoA inhibitory activities, with IC50 values of 1.17-1.84
      MUM. Among these, (E)-3-(3-(ethyl(quinolin-2-yl)amino)phenyl)acrylic acid (26 b)
      and (E)-3-(3-(butyl(quinolin-2-yl)amino)phenyl)acrylic acid (26 d) demonstrated
      noticeable vasorelaxation effects against phenylephrine-induced contraction in
      thoracic aorta artery rings, and compound 26 b had good water solubility and
      showed significant in vivo efficacy, which was similar to that of 5-(1,4
      diazepane-1-sulfonyl)isoquinoline (fasudil) in a subarachnoid hemorrhage
      cardiovascular model. To the best of our knowledge, compound 26 b is the first
      example of a small- molecule RhoA inhibitor with potent in vivo efficacy, which
      could serve as a good lead for designing cardiovascular agents. 

PMID- 25377277
TI  - Brief reports: Controlling the survival of human pluripotent stem cells by small
      molecule-based targeting of topoisomerase II alpha.
AB  - Pluripotent-specific inhibitors (PluriSIns) make a powerful tool to study the
      mechanisms controlling the survival of human pluripotent stem cells (hPSCs).
      Here, we characterize the mechanism of action of PluriSIn#2, a compound that
      selectively eliminates undifferentiated hPSCs, while sparing various other cell
      types derived from them. Toxicogenomic analysis predicts this compound to be a
      topoisomerase inhibitor. Gene expression analyses reveal that one of the human
      topoisomerase enzymes, topoisomerase II alpha (TOP2A), is uniquely expressed in
      hPSCs: TOP2A is highly expressed in undifferentiated cells, is downregulated
      during their differentiation, and its expression depends on the expression of
      core pluripotency transcription factors. Furthermore, siRNA-based knockdown of
      TOP2A in undifferentiated hPSCs results in their cell death, revealing that TOP2A
      expression is required for the survival of these cells. We find that PluriSIn#2
      does not directly inhibit TOP2A enzymatic activity, but rather selectively
      represses its transcription, thereby significantly reducing TOP2A protein levels.
      As undifferentiated hPSCs require TOP2A activity for their survival, TOP2A
      inhibition by PluriSIn#2 thus causes their cell death. Therefore, TOP2A
      dependency can be harnessed for the selective elimination of tumorigenic hPSCs
      from culture.

PMID- 25377278
TI  - 10-kHz High-Frequency SCS Therapy: A Clinical Summary.
AB  - OBJECTIVE: Chronic pain remains a serious public health problem worldwide. A
      spinal cord stimulation (SCS) therapy called HF10 SCS uses 10-kHz high-frequency
      stimulation to provide pain relief without paresthesia. In this article, we
      describe the therapy, device, and the methods of implant and then review the
      safety and effectiveness data for this therapy. RESULTS: HF10 SCS uses a charge
      balanced stimulation waveform that has been shown to be safe in both animal and
      human studies. Data from a multicenter, prospective clinical trial shows that the
      therapy provides substantial back and leg pain relief. Numerous additional
      reports suggest improved pain relief in other body areas and for complex pain
      patterns, even for patients who have previously failed other neuromodulation
      therapies. CONCLUSIONS: The clinical experience reported in this article supports
      the efficacy and pain relief provided by HF10 SCS therapy. Clinical studies have
      also concluded that HF10 SCS does not generate paresthesia nor was it necessary
      to provide adequate coverage for pain relief. As clinical evidence accumulates
      and technological innovation improves patient outcomes, neuromodulatory
      techniques will be sought earlier in the treatment continuum to reduce the
      suffering for the many with otherwise intractable chronic pain.

PMID- 25377279
TI  - Cerebral amyloid angiopathy related hemorrhage after stroke thrombolysis: case
      report and literature review.
AB  - Cerebral amyloid angiopathy (CAA) predisposes to symptomatic intracerebral
      hemorrhage (sICH) after combined thrombolytic and anticoagulant treatment of
      acute myocardial infarction. However, the role of CAA in stroke thrombolysis has
      not been established. Here, we describe a confirmed case of CAA-related
      hemorrhage in a patient receiving thrombolysis for acute ischemic stroke. On
      autopsy, immunohistochemistry revealed amyloid-beta positive staining in
      thickened cortical and meningeal arteries at sites of hemorrhage. Further
      research is urgently needed to determine the hemorrhage risk related to CAA in
      stroke thrombolysis and develop better diagnostic tools to identify CAA in the
      emergency room.

PMID- 25377280
TI  - Transplanted glial restricted precursor cells improve neurobehavioral and
      neuropathological outcomes in a mouse model of neonatal white matter injury
      despite limited cell survival.
AB  - OBJECTIVE: Neonatal white matter injury (NWMI) is the leading cause of cerebral
      palsy and other neurocognitive deficits in prematurely-born children, and no
      restorative therapies exist. Our objective was to determine the fate and effect
      of glial restricted precursor cell (GRP) transplantation in an ischemic mouse
      model of NWMI. METHODS: Neonatal CD-1 mice underwent unilateral carotid artery
      ligation on postnatal-Day 5 (P5). At P22, intracallosal injections of either
      enhanced green fluorescent protein (eGFP) + GRPs or saline were performed in
      control and ligated mice. Neurobehavioral and postmortem studies were performed
      at 4 and 8 weeks post-transplantation. RESULTS: GRP survival was comparable at 1
      month but significantly lower at 2 months post-transplantation in NWMI mice
      compared with unligated controls. Surviving cells showed better migration
      capability in controls; however, the differentiation capacity of transplanted
      cells was similar in control and NWMI. Saline-treated NWMI mice showed
      significantly altered response in startle amplitude and prepulse inhibition (PPI)
      paradigms compared with unligated controls, while these behavioral tests were
      completely normal in GRP-transplanted animals. Similarly, there was significant
      increase in hemispheric myelin basic protein density, along with significant
      decrease in pathologic axonal staining in cell-treated NWMI mice compared with
      saline-treated NWMI animals. INTERPRETATION: The reduced long-term survival and
      migration of transplanted GRPs in an ischemia-induced NWMI model suggests that
      neonatal ischemia leads to long-lasting detrimental effects on oligodendroglia
      even months after the initial insult. Despite limited GRP-survival, behavioral,
      and neuropathological outcomes were improved after GRP-transplantation. Our
      results suggest that exogenous GRPs improve myelination through trophic effects
      in addition to differentiation into mature oligodendrocytes.

PMID- 25377281
TI  - A preliminary study on the role of the complement regulatory protein, cluster of
      differentiation 55, in mice with diabetic neuropathic pain.
AB  - The aim of this study was to investigate the role of the complement regulatory
      protein cluster of differentiation 55 (CD55) in the pathogenesis of diabetic
      neuropathic pain (DNP). Healthy adult male C57BL/6J mice were intraperitoneally
      injected with streptozotocin (STZ) in order to induce DNP. Peripheral blood
      glucose and protein, and the mRNA expression levels of C3 and CD55 in the spinal
      cord were determined. In addition, the behaviors of these mice were observed. The
      results showed that STZ-treated mice displayed the clinical manifestations of
      diabetes mellitus, and that their peripheral blood glucose was markedly
      increased. On the 21st and 28th days following the STZ injection, the mechanical
      pain threshold and thermal pain threshold of the mice were dramatically reduced
      (P<0.05). |Additionally, 14 days post-STZ injection, the mRNA expression of C3 in
      the spinal cord was significantly increased, which continued for 28 days. On the
      21st and 28th days, the number of C3 positive cells in the spinal cord was
      markedly increased. Seven days after the STZ injection, the number of cells
      positive for CD55 was markedly reduced in the spinal dorsal horn and subsequently
      remained at a low level. The mRNA expression of CD55 also was significantly
      reduced (P<0.05) and remained so for 28 days. The reduction in the expression
      levels of CD55 occurred earlier than the changes in the expression of C3,
      suggesting that the downregulation of CD55 expression precedes, and has an
      important role regarding, the activation of C3 in the occurrence and development
      of DNP.

PMID- 25377283
TI  - Erratum to: NTBC treatment of the pyomelanogenic Pseudomonas aeruginosa clinical
      isolate PA1111 inhibits pigment production and increases sensitivity to oxidative
      stress.

PMID- 25377282
TI  - Diagnosis of muscle diseases presenting with early respiratory failure.
AB  - Here we describe a clinical approach and differential diagnosis for chronic
      muscle diseases which include early respiratory failure as a prominent feature in
      their presentation (i.e. respiratory failure whilst still ambulant). These
      patients typically present to neurology or respiratory medicine out-patient
      clinics and a distinct differential diagnosis of neuromuscular aetiologies should
      be considered. Amyotrophic lateral sclerosis and myasthenia gravis are the
      important non-muscle diseases to consider, but once these have been excluded
      there remains a challenging differential diagnosis of muscle conditions, which
      will be the focus of this review. The key points in the diagnosis of these
      disorders are being aware of relevant symptoms, which are initially caused by
      nocturnal hypoventilation or diaphragmatic weakness; and identifying other
      features which direct further investigation. Important muscle diseases to
      identify, because their diagnosis has disease-specific management implications,
      include adult-onset Pompe disease, inflammatory myopathy, and sporadic adult
      onset nemaline myopathy. Cases which are due to metabolic myopathy or muscular
      dystrophy are important to diagnose because of their implications for genetic
      counselling. Myopathy from sarcoidosis and colchicine each has a single reported
      case with this presentation, but should be considered because they are treatable.
      Disorders which have recently had their genetic aetiologies identified include
      hereditary myopathy with early respiratory failure (due to TTN mutations), the
      FHL1-related syndromes, and myofibrillar myopathy due to BAG3 mutation. Recently
      described syndromes include oculopharyngodistal muscular dystrophy that awaits
      genetic characterisation. 

PMID- 25377285
TI  - [Awake during the day & asleep at night - regulation, disorders and treatment].

PMID- 25377284
TI  - Comparison of genome sequencing technology and assembly methods for the analysis
      of a GC-rich bacterial genome.
AB  - Improvements in technology and decreases in price have made de novo bacterial
      genomic sequencing a reality for many researchers, but it has created a need to
      evaluate the methods for generating a complete and accurate genome assembly. We
      sequenced the GC-rich Caulobacter henricii genome using the Illumina MiSeq, Roche
      454, and Pacific Biosciences RS II sequencing systems. To generate a complete
      genome sequence, we performed assemblies using eight readily available programs
      and found that builds using the Illumina MiSeq and the Roche 454 data produced
      accurate yet numerous contigs. SPAdes performed the best followed by PANDAseq. In
      contrast, the Celera assembler produced a single genomic contig using the Pacific
      Biosciences data after error correction with the Illumina MiSeq data. In
      addition, we duplicated this build using the Pacific Biosciences data with
      HGAP2.0. The accuracy of these builds was verified by pulsed-field gel
      electrophoresis of genomic DNA cut with restriction enzymes.

PMID- 25377286
TI  - [Biological rhythm, sleep and jet lag].
AB  - Sleep is an active recovery process, which is governed by biological rhythms.
      This rhythmic variation influences almost all bodily functions and dictates the
      optimal time for sleep. Sleep itself is an inconsistent state mainly
      characterized by the alteration between REM and NREM sleep. Vital regenerative
      processes occur during sleep. Sleep is a basic prerequisite for wellbeing, health
      and performance. If the synchronization between sleep and the biological rhythms
      is disturbed, malfunctions of the organism have to be expected. Such a state can
      be found by a sudden shift of local time by travelling across time zones (jet
      lag). Therapeutic strategies can reduce the symptoms associated with the state of
      jet lag. 

PMID- 25377287
TI  - [Sleep habits, sleep quality and sleep medicine use of the Swiss population
      result].
AB  - A survey in a representative sample of the Swiss population revealed an average
      sleep duration of 7.5 hours on workdays and of 8.5 hours on free days, which
      reflected a more than half an hour (38 min) shorter sleep duration than 28 years
      ago. The mean time in bed was between 22:41 and 06:37 on workdays and between
      23:29 and 08:27 on free days. On workdays as well as on free days the bedtime was
      delayed by 47 minutes in comparison to a similar survey 28 years ago. By
      contrast, the mean rise times on workdays and free days did not change. The sleep
      duration required to feel refreshed was indicated with 7 hours, which was 41
      minutes less than 28 years ago. Roughly 90 % of the interviewees answered that
      they felt healthy, and 75 % described their sleep as good or very good compared
      to 79 % 28 years ago. The most frequent reasons stated for bad sleep were
      personal problems and strain at the workplace. The effect of bad quality sleep on
      every day functioning was considered as essential by 65 % of the respondents
      compared to 69 % 28 years ago. The use of medication to improve sleep was
      declared by 2.8 % (2.7 % 28 years ago), most often benzodiazepines, but also
      Valerian products and so-called z-drugs. In comparison with similar surveys in
      other countries (France, Great Britain and USA), Swiss residents slept roughly
      half an hour longer, but these other countries alike showed a sizable shortening
      of their habitual sleep duration over the last decades. 

PMID- 25377288
TI  - [Sleep physiology and its relevance for the management of behavioral sleep
      disorders in children].
AB  - Sleep problems are among the most frequent behavioural issues during childhood.
      This article highlights some of the most important aspects of children's sleep
      physiology and presents a clinical approach for the management of behavioural
      sleep disorders in children. Our concept is based on developmental aspects of
      sleep physiology and also uses behavioural strategies for the parents and their
      child to handle maladaptive sleep behaviour. 

PMID- 25377289
TI  - [Sleep and biological clock in the elderly].
AB  - This article gives an overview of factors underlying age-related changes in sleep
      wake behavior in healthy older humans. The self-regulation of the sleep-wake
      cycle [sleep-wake homeostasis] and the circadian clock, represent primary factors
      responsible for changes in sleep with age. As a matter of fact older healthy
      adults have a more superficial and less consolidated sleep and go to bed earlier
      compared to younger ages. Furthermore, sleep in healthy older people is more
      vulnerable to disturbances such as circadian desynchronisation and the lack of
      zeitgebers [insufficient light during the day]. 

PMID- 25377290
TI  - [Circadian rhythm sleep disorders in psychiatric diseases].
AB  - Circadian rhythm sleep disorders are prevalent among psychiatric patients. This
      is most probable due to a close relationship between functional disturbances of
      the internal clock, sleep regulation and mental health. Mechanisms on molecular
      level of the circadian clock and neurotransmitter signalling are involved in the
      development of both disorders. Moreover, circadian disorders and psychiatric
      diseases favour each other by accessory symptoms such as stress or social
      isolation. Actimetry to objectively quantify the rest-activity cycle and salivary
      melatonin profiles as marker for the circadian phase help to diagnose circadian
      rhythm sleep disorders in psychiatric patients. Chronotherapeutics such as bright
      light therapy, dark therapy, melatonin administration, and wake therapy are used
      to synchronise and consolidate circadian rhythms and help in the treatment of
      depression and other psychiatric disorders, but are still neglected in medicine.
      More molecular to behavioural research is needed for the understanding of the
      development of circadian disorders and their relationship to psychiatric
      illnesses. This will help to boost the awareness and treatment of circadian
      rhythm sleep disorders in psychiatry. 

PMID- 25377291
TI  - [Neurological sleep disorders].
AB  - Neurological sleep disorders are common in the general population and may have a
      strong impact on quality of life. General practitioners play a key role in
      recognizing and managing sleep disorders in the general population. They should
      therefore be familiar with the most important neurological sleep disorders. This
      review provides a comprehensive overview of the most prevalent and important
      neurological sleep disorders, including Restless legs syndrome (with and without
      periodic limb movements in sleep), narcolepsy, NREM- and REM-sleep parasomnias
      and the complex relationship between sleep and epilepsies. Although narcolepsy is
      considered as a rare disease, recent discoveries in narcolepsy research provided
      insight in the function of brain circuitries involved in sleep wake regulation.
      REM sleep behavioral parasomnia (RBD) is increasingly recognized to represent an
      early manifestation of neurodegenerative disorders, in particular evolving
      synucleinopathies. Early diagnosis may thus open new perspectives for developing
      novel treatment options by targeting neuroprotective substances. 

PMID- 25377292
TI  - [Daytime sleepiness and driving behaviour].
AB  - Daytime sleepiness is reported by 10-15 % within the general population of
      industrialised countries. According to federal statistics in Switzerland, only
      ~1.5 % of motor vehicle crashes are caused by excessive daytime sleepiness, which
      is in sharp contrast to the scientific literature, indicating a figure of 10 to
      30 %. This is most likely related to the difficulty to detect the underlying
      sleepiness by police officers and their low awareness of this cause in case of
      car accidents. As a consequence of this massively reduced figure, the real
      problem is underestimated and countermeasures as well as examinations of drivers
      at fault are inadequately realised in our country. The risk factors for
      sleepiness induced accidents are young age, male sex, driving at night or long
      distances and a number of diseases or sedative drugs. The most prevalent cause of
      sleepiness related accidents is the behaviourally induced sleep insufficiency
      syndrome or irregular sleep-wake rhythm in otherwise healthy subjects. Disease
      related sleepiness which may also cause motor vehicle accidents must be managed
      by physicians. In the diagnostic work-up sedative drugs, medical causes of
      sleepiness or tiredness as well as primary sleep-wake disorders must be
      considered. The most important duty of the treating physician, in addition to
      correct diagnosis and treatment, is to inform the affected patient of his or her
      responsibility not to drive while sleepy, about the theoretical legal
      consequences in case of an accident and about efficient countermeasures such as
      stopping in a rest area, drinking coffee, and taking a nap. For legal reasons,
      this information must be written in the patient's notes. Professional drivers
      suffering from sleep apnoea syndrome or other disorders with excessive daytime
      sleepiness, or private drivers who have already experienced a sleepiness induced
      accident, should be referred to a sleep-wake-centre for objective assessment of
      their sleepiness in the maintenance of wakefulness test or a driving simulator
      before they continue to drive. 

PMID- 25377293
TI  - [Non-pharmacological treatment of insomnia].
AB  - Chronic insomnia, i. e. complaints about prolonged sleep onset, difficulties in
      maintaining sleep, early morning awakening and associated impairments of daytime
      functioning afflicts approximately 10 % of the population in most Western
      industrialized countries. Chronic insomnia can be due to somatic disorders,
      mental disorders, intake of medications, legal or illicit drugs. One third of all
      patients with chronic insomnias suffers from primary insomnia, a diagnosis which
      is given when none of the above mentioned factors can be identified as a causal
      factor. In medical practice, insomnia usually is treated with hypnotic drugs or
      other sedative drugs such as antidepressants. In the last 20 years it was shown
      that cognitive-behavioral therapy for insomnia can be applied successfully
      independent of causal factors. Cognitive-behavioral treatment for insomnia (CBT
      I) encompasses psychoeducation about sleep and sleep hygiene, relaxation
      techniques, i. e. progressive muscle relaxation, specific behavioral techniques
      like stimulus control or sleep restriction and cognitive techniques to reduce
      nocturnal ruminations. Several published meta-analyses from the last two decades
      showed that these techniques, especially in their combined form, can be
      considered as evidence-based. It was shown that they are as effective as
      pharmacological therapy in the short-term and in the long-run even superior to
      pharmacotherapy. Cognitive-behavioral techniques for the therapy of insomnia can
      be used very successfully by trained physicians and psychotherapists. 

PMID- 25377294
TI  - Contribution of behavioral and cognitive therapy to managing overactive bladder
      syndrome in women in the absence of contributive urodynamic diagnosis.
AB  - Overactive bladder (OAB) is a syndrome characterized by symptoms of urgency with
      or without incontinence, frequency, and nocturia. Pathophysiology of OAB is
      incompletely characterized. Therefore, there is great variability surrounding OAB
      evaluation. In some cases, urodynamics is normal and the challenge is to propose
      the least invasive treatment. Behavioral therapies have been used for decades as
      they are conservative, inexpensive, and do not induce side effect. Our purpose
      was to describe which usual techniques of pelvic floor rehabilitation in
      association with behavioral and cognitive therapy could be proposed to manage OAB
      syndrome in the absence of urodynamic diagnosis and when no targeting drug
      treatment could be proposed. 

PMID- 25377295
TI  - Histopathology of excised midurethral sling mesh.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the
      histological characteristics of pathological specimens of excised midurethral
      sling mesh and surrounding vaginal tissue in patients who presented
      preoperatively with pain and/or exposure of mesh to patients who underwent mesh
      excision for voiding dysfunction without pain and/or erosion. METHODS: This is a
      retrospective case-control study of women who underwent excision of midurethral
      sling mesh between 2008 and 2013. Three groups were identified: (1) voiding
      dysfunction without pain or exposure (control group), (2) pain and/or mesh
      exposure, and (3) voiding dysfunction with pain and/or mesh exposure. All
      original pathological specimens were rereviewed by one pathologist blinded to
      indication for excision and the previous pathology report. Degree of inflammation
      and fibrosis were recorded based on a 4-point scale along with the presence of
      giant cell reaction. RESULTS: A total of 130 subjects met inclusion criteria: 60
      (46.2 %) with voiding dysfunction only, 21 (16.2 %) with pain/erosion, and 49
      (37.7 %) with both pain/exposure and voiding dysfunction. The voiding dysfunction
      only group was found to have significantly higher levels of inflammation, median
      grade 2 (1-3), compared to the other two groups with a p value of 0.007. There
      were no statistical differences in fibrosis and giant cell reaction between the
      three groups. CONCLUSIONS: Midurethral sling mesh excised for voiding dysfunction
      demonstrates elevated levels of inflammation compared to mesh that is excised for
      pain and/or exposure. The vaginal tissue fibrosis and giant cell reaction are
      similar in patients who undergo mesh excision for voiding dysfunction and pain,
      and/or mesh exposure.

PMID- 25377297
TI  - Effectiveness of a new standardised Urinary Continence Physiotherapy Programme
      for community-dwelling older women in Hong Kong.
AB  - OBJECTIVE: To examine the effectiveness of a standardised Urinary Continence
      Physiotherapy Programme for older Chinese women with stress, urge, or mixed
      urinary incontinence. DESIGN: A controlled trial. SETTING: Six elderly community
      health centres in Hong Kong. PARTICIPANTS: A total of 55 women aged over 65 years
      with mild-to-moderate urinary incontinence. INTERVENTIONS: Participants were
      randomly assigned to the intervention group (n=27) where they received eight
      sessions of Urinary Continence Physiotherapy Programme for 12 weeks. This group
      received education about urinary incontinence, pelvic floor muscle training with
      manual palpation and verbal feedback, and behavioural therapy. The control group
      (n=28) was given advice and an educational pamphlet on urinary incontinence.
      RESULTS: There was significant improvement in urinary symptoms in the
      intervention group, especially in the first 5 weeks. Compared with the control
      group, participants receiving the intervention showed significant reduction in
      urinary incontinence episodes per week with a mean difference of -6.4 (95%
      confidence interval, -8.9 to -3.9; t= -5.3; P<0.001) and significant improvement
      of quality of life with a mean difference of -3.93 (95% confidence interval, 
      5.08 to -2.78; t= -6.9; P<0.001) measured by Incontinence Impact Questionnaire
      Short Form modified Chinese (Taiwan) version. The subjective perception of
      improvement, measured by an 11-point visual analogue scale, was markedly better
      in the intervention group (mean, 8.7; standard deviation, 1.0; 95% confidence
      interval, 8.4-9.1) than in the control group (mean, 1.4; standard deviation, 0.7;
      95% confidence interval, 1.2-1.7; t=33.9; P<0.001). The mean treatment
      satisfaction in the intervention group was 9.5 (standard deviation, 0.8) as
      measured by an 11-point visual analogue scale. CONCLUSIONS: This study
      demonstrated that the Urinary Continence Physiotherapy Programme was effective in
      alleviating urinary symptoms among older Chinese women with mild-to-moderate
      heterogeneous urinary incontinence.

PMID- 25377296
TI  - Innovative pharmacotherapies for women with overactive bladder: where are we now
      and what is in the pipeline?
AB  - INTRODUCTION AND HYPOTHESIS: The impressive prevalence of overactive bladder
      (OAB) and the relevant limitations of current treatments urge the need for novel
      therapeutic approaches. METHODS: A systematic literature and web search was
      performed to identify investigational drugs that entered the early and late
      phases of clinical development for women with OAB symptoms. RESULTS: Approved
      pharmacological therapies for OAB (antimuscarinics, beta-3 agonists, and
      botulinum toxin) are evolving with the development of alternative administration
      methods, combination strategies, and novel compounds, expected to improve
      effectiveness, bladder selectivity, and dose flexibility. A wealth of
      investigational compounds, developed with both public and companies' indoor
      nonclinical disease-oriented studies, entered the early and late stages of
      clinical development in the last decade. Most non-anticholinergic compounds in
      ongoing clinical trials target central and peripheral neurotransmitter receptors
      involved in neurological modulation of micturition, nonadrenergic-noncholinergic
      mechanisms, cyclic nucleotide metabolism, different subtypes of ion channels or
      peripheral receptors of prostaglandins, vanilloids, vitamin D3, and opioids.
      Fascinating advances are ongoing also in the field of genetic therapy.
      CONCLUSIONS: New pharmaceutical formulations and drug combinations are expected
      to be available in the next decade in order to overcome the limitations of
      current drugs for OAB. Although proof-of-concept, patient-oriented studies
      yielded disappointing results for several tentative drugs, a lot of clinical
      research is ongoing that is expected to provide clinicians with novel therapeutic
      agents in the near future.

PMID- 25377298
TI  - The benefit of prothrombin complex concentrate in decreasing neurological
      deterioration in patients with warfarin-associated intracerebral haemorrhage.
AB  - OBJECTIVE: To compare the outcomes of patients with warfarin-associated
      intracerebral haemorrhage given different treatments to reverse the effect of
      anticoagulation. DESIGN: Historical cohort study. SETTING: A regional hospital in
      Hong Kong. PATIENTS: Patients on warfarin who developed intracerebral
      haemorrhage. INTERVENTIONS: Prothrombin complex concentrate versus fresh frozen
      plasma treatment. MAIN OUTCOME MEASURES: The primary outcome measures included
      the international normalised ratio before and after prothrombin complex
      concentrate treatment and the neurological deterioration in patients with Glasgow
      Coma Scale score of more than 8/not intubated/not planned for immediate surgery
      (target group). Secondary outcome measures were haematoma expansion, 7-day and 30
      day mortality rates, and 3-month functional outcome. Safety outcome was the
      occurrence of a thrombotic event after prothrombin complex concentrate treatment
      within the index admission. RESULTS: Among 33 patients with clearly documented
      time of infusion of prothrombin complex concentrate, and whose international
      normalised ratio was checked before and after prothrombin complex concentrate
      treatment, the mean international normalised ratio was reduced from 2.81 to 1.21
      within 24 hours. Within the target group of patients, there was a significantly
      lower rate of neurological deterioration in the prothrombin complex concentrate
      group (17.4% of 23 patients) versus fresh frozen plasma group (45.5% of 33
      patients) [P=0.027]. In terms of the 7-day mortality, 30-day mortality, and 3
      month functional outcome, prothrombin complex concentrate-treated group showed a
      favourable trend although the difference did not reach a statistical
      significance. No patient developed thrombotic complications after prothrombin
      complex concentrate treatment. CONCLUSIONS: Prothrombin complex concentrates can
      reverse the warfarin effect of prolonged international normalised ratio in a
      timely manner. It might better improve the outcome of warfarin-associated
      intracerebral haemorrhage compared with fresh frozen plasma treatment by
      reduction in neurological deterioration.

PMID- 25377299
TI  - 1-Adamantanethiol as a versatile nanografting tool.
AB  - Strategies to regulate the self-assembly of adsorbates to create surface
      structures with molecular-scale features and organization are of broad interest
      to nanoscience, biochemistry, and engineering. One approach utilizes molecules
      with tailored intermolecular interaction strengths and topologies to direct
      molecular self-assembly as exemplified by the adsorption of 1-adamantanethiol
      molecules on Au{111} substrates. 1-Adamantanethiolate self-assembled monolayers
      exhibit decreased packing densities and weaker intermolecular interaction
      strengths than n-alkanethiolate self-assembled monolayers, which result in their
      complete displacement upon exposure to n-alkanethiol molecules. Herein, we
      explore the capabilities of the atomic force microscopy-based lithographic
      technique, nanografting, to fabricate chemical patterns comprised of 1
      adamantanethiolate monolayers. Positive 1-adamantanethiolate patterns are
      generated by nanografting 1-adamantanethiol molecules into preexisting n
      alkanethiolate self-assembled monolayers, and negative 1-adamantanethiolate
      patterns are created by nanografting n-alkanethiol molecules into preexisting 1
      adamantanethiolate self-assembled monolayers. The patterned 1-adamantanethiolate
      regions are displaced upon exposure to solutions of n-alkanethiol molecules. This
      two-step nanografting-displacement strategy minimizes pattern dissolution as 1
      adamantanethiol molecules do not intercalate into the preexisting self-assembled
      monolayer during nanografting. 1-Adamantanethiol can be utilized create high
      resolution sacrificial chemical patterns with feature sizes beyond those afforded
      other 1-adamantanethiol patterning strategies for applications such as resists
      for metallic and organic structures.

PMID- 25377300
TI  - The contributions of oxidative stress, oxidised lipoproteins and AMPK towards
      exercise-associated PPARgamma signalling within human monocytic cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to be
      activated via exercise-associated transient increases in oxidative stress.
      However, the precise mechanism(s) triggering PPARgamma activation in monocytes
      during/following exercise remain to be confirmed. Here, two cohorts of five
      healthy male individuals undertook exercise bouts (cycling; 70% VO2max; 45 min)
      in the presence/absence of dietary antioxidant supplementation (vitamins C (1000
      mg/day) and E (400IU/day) for four weeks before exercise); monocytic 5' adenosine
      monophosphate-activated protein kinase (AMPK)/PPARgamma co-activator-1alpha (PGC
      1alpha)/PPARgamma signalling was investigated in samples obtained before exercise
      and up to 24 h after exercise, while THP-1 cells were cultured as an in vitro
      monocyte model. In THP-1 cells, AMPKalpha1 was phosphorylated within 1h of
      menadione (15 MUM)-triggered increases in [reactive oxygen species (ROS)]cyto, an
      effect which was followed by upregulation of PPARgamma and several of its target
      genes (PGC-1alpha, liver X receptor alpha [LXRalpha] and ATP-binding cassette
      subfamily A, member 1 [ABCA1]; 24-72 h), with these effects being blunted by co
      administration of vitamin C (62.5 MUM). Conversely, treatment with oxidised low
      density lipoprotein (oxLDL) (1 MUg/mL; 24-72 h), but not non-oxidised LDL,
      upregulated the above PPARgamma-regulated genes without affecting AMPKalpha1
      phosphorylation. In vivo, dietary antioxidant supplementation (which is known to
      prevent exercise-triggered increases in oxLDL levels) blunted exercise-associated
      upregulation of the above PPARgamma-regulated genes, but had no effect on
      exercise-associated transient [ROS]cyto increases, or on AMPK phosphorylation.
      These data suggest that exercise-associated PPARgamma signalling effects appear,
      at least in monocytes, to be mediated by increased generation of PPARgamma
      ligands via oxidation of lipoproteins (following exercise-associated transient
      increases in oxidative stress), rather than via [ROS]cyto-mediated AMPK
      activation. These findings may be of clinical relevance, as PPARgamma activation
      in monocytes is associated with beneficial effects related to type-2 diabetes and
      its cardiovascular complications.

PMID- 25377301
TI  - Direct Extraction of Alignment Moments from Inelastic Scattering Images.
AB  - We present a novel means of analyzing velocity-map images of angular momentum
      polarization in inelastic scattering. In this approach, linear combinations of
      angular distributions obtained by integrating select regions of images for two
      probe laser polarizations directly yield the alignment-free differential cross
      sections and the differential alignment moments. No fitting is needed in the
      analysis. The method relies on the fact that the angular distribution for out-of
      plane scattering is encoded in the distribution along the relative velocity
      vector, and this may be recovered quantitatively owing to the redundancy of the
      in-plane and out-of-plane scattering for the horizontal polarization case. 

PMID- 25377302
TI  - Preliminary results for the use of knee mega-endoprosthesis in the treatment of
      musculoskeletal complications of haemophilia.
AB  - Complications of haemophilia in the knee region are rare and difficult to treat.
      Use of surgical treatments such as total knee arthroplasty cannot satisfactorily
      restore knee function in patients with these complications, which include massive
      haemophilic pseudotumour, fracture around the knee and haemarthrosis. To analyse
      the postoperative results of patients suffering from complications of haemophilia
      and treated with a knee mega-endoprosthesis, to discuss and compare this type of
      surgical management with other types of treatments used in similar cases. We
      retrospectively analyse the surgical results of patients who were treated with a
      knee mega-endoprosthesis for complications of haemophilia. Three severe
      haemophilic arthritic knees, of which two were combined with femoral condylar
      fractures, were treated in a one-stage surgery, and another two knees which
      presented with massive haemophilic pseudotumours and bony defects were treated in
      a two-stage operation. Mean age at time of surgery was 28.5 years old and mean
      follow-up time was 22.8 months; the mega-endoprosthesis surgery was successfully
      performed in four cases and the mean range of motion increased from 29.5 degrees 
      preoperatively to 96.75 degrees  postoperatively. The Knee society score function
      score value increased from 25 to 82.5. One knee was amputated because of
      uncontrollable recurrent haemorrhage. Roentgenograms did not show any signs of
      loosening of the prostheses. Use of Mega-endoprosthesis in the treatment of
      complications of haemophilia can offer patients suffering from massive
      pseudotumours with bone defect, severe contracture knee haemophilic arthritis and
      fractures around a haemophilic knee a viable treatment option.

PMID- 25377303
TI  - Impact of roles assignation on heterogeneous populations in evolutionary dictator
      game.
AB  - The evolution of cooperation is a hot and challenging topic in the field of
      evolutionary game theory. Altruistic behavior, as a particular form of
      cooperation, has been widely studied by the ultimatum game but not by the
      dictator game, which provides a more elegant way to identify the altruistic
      component of behaviors. In this paper, the evolutionary dictator game is applied
      to model the real motivations of altruism. A degree-based regime is utilized to
      assess the impact of the assignation of roles on evolutionary outcome in
      populations of heterogeneous structure with two kinds of strategic updating
      mechanisms, which are based on Darwin's theory of evolution and punctuated
      equilibrium, respectively. The results show that the evolutionary outcome is
      affected by the role assignation and that this impact also depends on the
      strategic updating mechanisms, the function used to evaluate players' success,
      and the structure of populations. 

PMID- 25377304
TI  - Occupational contact dermatitis caused by omeprazole in a veterinary medicament.

PMID- 25377305
TI  - Occupational allergic contact dermatitis caused by omeprazole in a horse breeder.

PMID- 25377306
TI  - 'Allergyapp'--a novel app(lication) to detect contact allergens in cosmetic
      products.

PMID- 25377307
TI  - Contact dermatitis caused by ebony wood.

PMID- 25377309
TI  - Secure Secondary Use of Clinical Data with Cloud-based NLP Services. Towards a
      Highly Scalable Research Infrastructure.
AB  - OBJECTIVES: The secondary use of clinical data provides large opportunities for
      clinical and translational research as well as quality assurance projects. For
      such purposes, it is necessary to provide a flexible and scalable infrastructure
      that is compliant with privacy requirements. The major goals of the cloud4health
      project are to define such an architecture, to implement a technical prototype
      that fulfills these requirements and to evaluate it with three use cases.
      METHODS: The architecture provides components for multiple data provider sites
      such as hospitals to extract free text as well as structured data from local
      sources and de-identify such data for further anonymous or pseudonymous
      processing. Free text documentation is analyzed and transformed into structured
      information by text-mining services, which are provided within a cloud-computing
      environment. Thus, newly gained annotations can be integrated along with the
      already available structured data items and the resulting data sets can be
      uploaded to a central study portal for further analysis. RESULTS: Based on the
      architecture design, a prototype has been implemented and is under evaluation in
      three clinical use cases. Data from several hundred patients provided by a
      University Hospital and a private hospital chain have already been processed.
      CONCLUSIONS: Cloud4health has shown how existing components for secondary use of
      structured data can be complemented with text-mining in a privacy compliant
      manner. The cloud-computing paradigm allows a flexible and dynamically adaptable
      service provision that facilitates the adoption of services by data providers
      without own investments in respective hardware resources and software tools.

PMID- 25377308
TI  - Timing of elective delivery in gastroschisis: a decision and cost-effectiveness
      analysis.
AB  - OBJECTIVE: To determine the most cost-effective timing of delivery in pregnancies
      complicated by gastroschisis, using a decision-analytic model. METHODS: We
      created a decision-analytic model to compare planned delivery at 35, 36, 37, 38
      and 39 weeks' gestation. Outcomes considered were stillbirth, death within 1 year
      of birth and respiratory distress syndrome (RDS). Probability estimates of events
      (stillbirth, complex gastroschisis and RDS for each gestational age at delivery
      and risk of death with simple and complex gastroschisis), utilities and costs
      assigned to the outcomes were obtained from the published literature. Cost
      analysis was assessed from a societal perspective, using a willingness-to-pay
      threshold of $100,000 per surviving infant. Outcomes and costs were considered
      throughout 1 year of postnatal life. Multiway sensitivity analysis was performed
      to address uncertainties in baseline assumptions. RESULTS: In the base-case
      analysis, delivery at 38 weeks' gestation was the most cost-effective strategy.
      Planned delivery at 35 weeks was associated with the fewest stillbirths and
      deaths within 1 year of delivery, owing largely to a lower ongoing risk of
      stillbirth. In Monte Carlo simulation when every variable was varied over its
      entire range, delivery at 38 weeks was cost-effective compared to delivery at 39
      weeks in 76% of trials and delivery at 37 weeks was cost-effective in 69% of
      trials. Delivery at 38 weeks resulted in three additional cases of RDS for every
      100 stillbirths or deaths within 1 year that were prevented. CONCLUSIONS: For
      pregnancies complicated by gastroschisis, the most cost-effective timing of
      delivery is at 38 weeks. Few additional cases of RDS are caused for every one
      stillbirth or death within 1 year that was prevented with delivery at 37-38 weeks
      compared with at 39 weeks.

PMID- 25377310
TI  - Emerging concepts on the use of antiretroviral therapy in older adults living
      with HIV infection.
AB  - PURPOSE OF REVIEW: With the overwhelming success of combination antiretroviral
      therapy, HIV infection is now a chronic, but manageable, medical condition.
      Consequently, HIV-infected cohorts are ageing leading to new challenges in the
      life-long management of this condition. Here, we review recent data concerning
      the modern treatment of older HIV-infected adults. RECENT FINDINGS: HIV-infected
      cohorts are ageing with the majority of those infected predicted to be more than
      50 years old within the next 2 decades. There is emerging evidence of increased
      antiretroviral drug exposure in older individuals, but the evidence this leads to
      increased toxicity is less clear-cut. In addition, the choice of antiretroviral
      agents is more challenging in older HIV-infected patients because of the presence
      of comorbidities, which occur more commonly and at a younger age than in HIV
      uninfected individuals and because of a higher propensity for drug-drug
      interactions due to the use of concomitant medications. Specific recommendations
      regarding antiretroviral treatment of older HIV-infected individuals are lacking
      and prospective trials in older age groups are urgently needed. SUMMARY: The use
      of antiretroviral therapies in older individuals is complex. Development of novel
      antiretrovirals and antiretroviral combinations with a low propensity for
      toxicity, drug-drug interactions and reliable pharmacology regardless of age is
      urgently needed.

PMID- 25377311
TI  - Asymptomatic bacteriuria and urinary tract infections among renal allograft
      recipients.
AB  - PURPOSE OF REVIEW: Bacteriuria is common among renal allograft recipients. It can
      be categorized into asymptomatic bacteriuria (ASB) and urinary tract infection
      (UTI). However, in medical literature, the classifications of bacteriuria are
      often not clear or ASB is also classified as a UTI. This contributes to
      difficulties in interpretation of the incidence and risk factors of these two
      entities. In this review, we describe the epidemiology, risk factors, management
      and the impact on renal allograft function of these two entities separately
      according to the recent literature. RECENT FINDINGS: Risk factors for ASB are not
      completely comparable to the risk factors of UTIs. Persistent ASB has been
      associated with development of acute rejection and allograft pyelonephritis. The
      available data suggest that treatment of ASB is not very effective. Prophylaxis
      with trimethoprim-sulfamethoxazole does not prevent UTIs such as allograft
      pyelonephritis. Blood stream infections and emphysematous allograft
      pyelonephritis are associated with renal allograft loss. SUMMARY: ASB is the most
      common manifestation of bacteriuria after renal transplantation. More effective
      interventions are needed to prevent bacteriuria. Renal allograft recipients with
      persistent ASB should be closely monitored since they could be at risk for
      developing not only UTIs, such as allograft pyelonephritis, but also acute
      rejection.

PMID- 25377312
TI  - Perceptions and Challenges: Postpartum Care Among Korean Americans Through an
      Online Community.
AB  - PURPOSE: This study aims to obtain the understanding of Korean immigrants'
      postpartum care expectations and experiences as they tend to differ from the
      dominant culture in the United States. DESIGN: Using an interpretative
      qualitative method, 305 questions and 1,224 replies on a bulletin board forum in
      a major Korean online community were examined. The postings were identified
      through a keyword search and a subsequent categorization of the resulting
      questions. FINDINGS: A qualitative analysis provided descriptive knowledge
      regarding postpartum care and the associated beliefs widespread among Korean
      Americans, struggles with the issues they face during postpartum care, and the
      vulnerability of new Korean mothers to the negative effects of experiencing unmet
      needs. DISCUSSION: The results pointed to the significance of understanding the
      concerns regarding postpartum care needs among the Korean immigrant women.
      Furthermore, the outcomes illustrate the variations in cultural beliefs and
      practices of postpartum care needed for health care providers.

PMID- 25377313
TI  - Transcultural nursing scholars' corner: leadership in application and
      dissemination of concepts, models, and theories.

PMID- 25377314
TI  - Protein tyrosine phosphatase of liver regeneration-1 is required for normal
      timing of cell cycle progression during liver regeneration.
AB  - Protein tyrosine phosphatase of liver regeneration-1 (Prl-1) is an immediate
      early gene that is significantly induced during liver regeneration. Several in
      vitro studies have suggested that Prl-1 is important for the regulation of cell
      cycle progression. To evaluate its function in liver regeneration, we ablated the
      Prl-1 gene specifically in mouse hepatocytes using the Cre-loxP system. Prl-1
      mutant mice (Prl-1(loxP/loxP);AlfpCre) appeared normal and fertile. Liver size
      and metabolic function in Prl-1 mutants were comparable to controls, indicating
      that Prl-1 is dispensable for liver development, postnatal growth, and hepatocyte
      differentiation. Mutant mice demonstrated a delay in DNA synthesis after 70%
      partial hepatectomy, although ultimate liver mass restoration was not affected.
      At 40 h posthepatectomy, reduced protein levels of the cell cycle regulators
      cyclin E, cyclin A2, cyclin B1, and cyclin-dependent kinase 1 were observed in
      Prl-1 mutant liver. Investigation of the major signaling pathways involved in
      liver regeneration demonstrated that phosphorylation of protein kinase B (AKT)
      and signal transducer and activator of transcription (STAT) 3 were significantly
      reduced at 40 h posthepatectomy in Prl-1 mutants. Taken together, this study
      provides evidence that Prl-1 is required for proper timing of liver regeneration
      after partial hepatectomy. Prl-1 promotes G1/S progression via modulating
      expression of several cell cycle regulators through activation of the AKT and
      STAT3 signaling pathway. 

PMID- 25377315
TI  - Glucose-dependent insulinotropic polypeptide-mediated signaling pathways enhance
      apical PepT1 expression in intestinal epithelial cells.
AB  - We have shown recently that glucose-dependent insulinotropic polypeptide (GIP),
      but not glucagon-like peptide 1 (GLP-1) augments H(+) peptide cotransporter
      (PepT1)-mediated peptide absorption in murine jejunum. While we observed that
      inhibiting cAMP production decreased this augmentation of PepT1 activity by GIP,
      it was unclear whether PKA and/or other regulators of cAMP signaling pathway(s)
      were involved. This study utilized tritiated glycyl-sarcosine [(3)H-glycyl
      sarcosine (Gly-Sar), a relatively nonhydrolyzable dipeptide] uptake to measure
      PepT1 activity in CDX2-transfected IEC-6 (IEC-6/CDX2) cells, an absorptive
      intestinal epithelial cell model. Similar to our earlier observations with mouse
      jejunum, GIP but not GLP-1 augmented Gly-Sar uptake (control vs. +GIP: 154 +/- 22
      vs. 454 +/- 39 pmol/mg protein; P < 0.001) in IEC-6/CDX2 cells. Rp-cAMP (a PKA
      inhibitor) and wortmannin [phosophoinositide-3-kinase (PI3K) inhibitor]
      pretreatment completely blocked, whereas neither calphostin C (a potent PKC
      inhibitor) nor BAPTA (an intracellular Ca(2+) chelator) pretreatment affected the
      GIP-augmented Gly-Sar uptake in IEC-6/CDX2 cells. The downstream metabolites Epac
      (control vs. Epac agonist: 287 +/- 22 vs. 711 +/- 80 pmol/mg protein) and AKT
      (control vs. AKT inhibitor: 720 +/- 50 vs. 75 +/- 19 pmol/mg protein) were shown
      to be involved in GIP-augmented PepT1 activity as well. Western blot analyses
      revealed that both GIP and Epac agonist pretreatment enhance the PepT1 expression
      on the apical membranes, which is completely blocked by wortmannin in IEC-6/CDX2
      cells. These observations demonstrate that both cAMP and PI3K signaling pathways
      augment GIP-induced peptide uptake through Epac and AKT-mediated pathways in
      intestinal epithelial cells, respectively. In addition, these observations also
      indicate that both Epac and AKT-mediated signaling pathways increase apical
      membrane expression of PepT1 in intestinal absorptive epithelial cells. 

PMID- 25377316
TI  - Intestinal epithelial suppressor of cytokine signaling 3 enhances microbial
      induced inflammatory tumor necrosis factor-alpha, contributing to epithelial
      barrier dysfunction.
AB  - A single layer of intestinal epithelial cells (IEC) lines the entire
      gastrointestinal tract and provides the first line of defense and barrier against
      an abundance of microbial stimuli. IEC homeostasis and repair are mediated
      through microbe-sensing Toll-like receptor (TLR)-induced inflammatory pathways.
      Increasing evidence supports a role of suppressor of cytokine signaling 3 (SOCS3)
      as a modulator of IEC turnover, balancing controlled repair and replenishment
      with excessive IEC proliferation predisposing to dysplasia and cancer. Our data
      indicate that SOCS3 can limit microbial-induced IEC repair, potentially through
      promoting tumor necrosis factor-alpha (TNF-alpha) and limiting TNFR2 expression.
      Activation of TLR5 signaling pathways, compared with other TLR, increases TNF
      alpha mRNA in a dose-dependent manner and SOCS3 enhances TLR5-induced TNF-alpha.
      We also show that flagellin promotes transcription of TNFR2 and that SOCS3 limits
      this expression, presenting a mechanism of SOCS3 action. Our data also support
      the role of microbial ligands in epithelial wound healing and suggest that a
      functional consequence of increased TNF-alpha is reduced wound healing. These
      results provide further evidence to support the regulatory role of epithelial
      SOCS3 in intestinal health and suggest that the increased expression of SOCS3
      observed in IBD may serve to perpetuate "inflammation" by promoting TNF-alpha
      production and limiting epithelial repair in response to commensal microflora. 

PMID- 25377317
TI  - Aboriginal health: agreement between general practitioners and patients on their
      health risk status and screening history.
AB  - OBJECTIVE: To examine agreement between patients' self-report and general
      practitioners' perception of their patients' health risk status and screening
      history. METHODS: Patients attending an Aboriginal Community Controlled Health
      Service self-reported via survey their health risk status and screening history,
      while waiting to see their general practitioner (GP). Following the consultation
      the GP completed a corresponding survey. Prevalence rates and rates of agreement
      using the kappa statistic were calculated for both self-reported and GP-reported
      risk status for smoking, at-risk alcohol consumption and physical inactivity; and
      screening history for blood pressure, cholesterol, diabetes and cervical cancer.
      RESULTS: Prevalence rates of health risks were similar from self-report versus GP
      reported, yet differed on screening history. Patients who identified themselves
      as being at risk were often not the same as those identified by GPs. Agreement
      between patient and doctor was substantial for smoking, yet poor for at-risk
      alcohol consumption and physical inactivity. Agreement was fair for cholesterol
      and cervical cancer screening, and slight for blood pressure and diabetes
      screening. CONCLUSIONS AND IMPLICATIONS: This study suggests that for effective
      preventive care, using self-report for some health risks may be reliable, but
      less so for screening history. Greater assistance is needed in primary health
      care settings to identify patients who are at risk.

PMID- 25377319
TI  - Tissue factor pathway inhibitor: then and now.
AB  - Tissue factor pathway inhibitor (TFPI) is the major physiological regulator of
      tissue factor (TF)-induced blood coagulation. TFPI inhibits the TF-activated
      factor VII (FVIIa) complex in an activated factor X (FXa)-dependent manner,
      helping to control thrombin generation and ultimately fibrin formation. The
      importance of TFPI is demonstrated in models of hemophilia where lower levels of
      FVIII or FIX are insufficient to overcome its inhibitory effect, resulting in a
      bleeding phenotype. There are two major isoforms in vivo; TFPIalpha contains
      three Kunitz-type inhibitory domains (designated K1, K2, and K3), is secreted by
      endothelial cells and requires protein S to enhance its anticoagulant activity.
      In contrast, TFPIbeta contains only the K1 and K2 domains, but it is attached to
      the endothelial surface via a glycosylphosphatidylinositol anchor. This review
      will initially provide a brief history of the major discoveries related to TFPI,
      and then discuss new insights into the physiology of TFPI, including updates on
      its association with protein S and FV, as well as the current understanding of
      its association with disease. 

PMID- 25377318
TI  - Switching from body surface area-based to fixed dosing for the investigational
      proteasome inhibitor ixazomib: a population pharmacokinetic analysis.
AB  - AIMS: This population pharmacokinetic analysis of the investigational oral
      proteasome inhibitor ixazomib assessed the feasibility of switching from body
      surface area (BSA)-based to fixed dosing, and the impact of baseline covariates
      on ixazomib pharmacokinetics. METHODS: Data were pooled from 226 adult patients
      with multiple myeloma, lymphoma or solid tumours in four phase 1 studies, in
      which ixazomib dosing (oral/intravenous, once/twice weekly) was based on BSA.
      Population pharmacokinetic modelling was undertaken using nonmem version 7.2.
      RESULTS: Ixazomib pharmacokinetics were well described by a three compartment
      model with first order absorption and linear elimination. Ixazomib was absorbed
      rapidly (Ka 0.5 h(-1)), with dose- and time-independent pharmacokinetics.
      Estimated absolute bioavailability and clearance were 60% and 2l h(-1),
      respectively. Although a small effect of BSA (range 1.3-2.6 m(2)) was observed on
      the peripheral volume of distribution (V4), reducing the corresponding inter
      individual variability by 12.9%, there was no relationship between BSA and
      ixazomib clearance (the parameter that dictates total systemic exposure following
      fixed dosing). Consistently, based on simulations (n = 1000), median AUCs
      (including interquartile range) were similar after BSA-based (2.23 mg m(-2)) and
      fixed (4 mg) oral dosing with no trend in simulated AUC vs. BSA for fixed dosing
      (P = 0.42). No other covariates, including creatinine clearance (22-213.7 ml min(
      1)) and age (23-86 years), influenced ixazomib pharmacokinetics. CONCLUSIONS:
      This analysis supports a switch from BSA-based to fixed dosing, without dose
      modification for mild/moderate renal impairment or age, in future adult studies
      of ixazomib, simplifying dosing guidance and clinical development.

PMID- 25377320
TI  - Glycosaminoglycans: anticoagulant and nonanticoagulant actions: a short history
      of symposia held at villa vigoni.
AB  - Heparin, a sulfated polysaccharide belonging to the family of glycosaminoglycans,
      was discovered in the beginning of the 20th century and was initially identified
      as a procoagulant isolated from liver tissue. After the first application in
      patients approximately 30 years later, further purification identified the major
      as well as minor, but important, component units of the complex chain mixtures
      constituting heparin and the multiplex actions became a scientific challenge
      recently. A series of "Glycosaminoglycan symposium-anticoagulant and
      nonanticoagulant actions" developed over the past 20 years and focused on this
      topic has published research data in three issues of Seminars in Thrombosis &
      Hemostasis and in several other international scientific journals. The latest
      developments on the methods of analysis, the synthesis, the degradation by
      heparanases and the nonanticoagulant effects in tumor growth, in anti
      inflammatory diseases, and in Alzheimer diseases as presented in the 21st
      symposium are summarized in the present overview on the occasion of the 40th
      anniversary of the journal with special reference to the journal's founding
      Editor in Chief, Eberhard F. Mammen. 

PMID- 25377321
TI  - A short contemporary history of disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation (DIC) is a syndrome characterized by
      systemic intravascular activation of coagulation, leading to a widespread
      deposition of fibrin in the circulation. There is ample experimental and
      pathological evidence that the fibrin deposition contributes to multiple organ
      failure. The massive and ongoing activation of coagulation may result in
      depletion of platelets and coagulation factors, which may cause bleeding
      (consumption coagulopathy). The syndrome of DIC is well known in the medical
      literature for centuries, although a more precise description of the underlying
      mechanisms had to await the 20th century. Initial ideas on a role of the contact
      activation system as the primary trigger for the systemic activation of
      coagulation as well as a presumed hyperfibrinolytic response in DIC have been
      found to be misconceptions. Experimental and clinical evidence now indicate that
      the initiation of coagulation in DIC is caused by tissue factor expression, which
      in combination with downregulated physiological anticoagulant pathways and
      impaired fibrinolysis leads to widespread fibrin deposition. In addition, an
      extensive bidirectional interaction between coagulation and inflammation may
      further contribute to the pathogenesis of DIC. 

PMID- 25377322
TI  - Historical review on genetic analysis in hemophilia A.
AB  - Molecular genetic analysis is widely applied in inherited bleeding disorders. The
      outcome of genetic analysis allows genetic counselling in affected families and
      helps to find a link between the genotype and phenotype. Genetic analysis in
      hemophilia A (HA) has tremendously improved in the past decades. Many new
      techniques and modifications as well as analysis software have become available,
      which has enabled genetic analysis and interpretation of data to become faster
      and more accurate. The advances in mutation detection strategies facilitate the
      identification of the causal mutation in up to 97% of patients with HA. This
      review discusses the milestones in genetic analysis of HA and highlights the
      importance of identification of the causative mutations for genetic counseling
      and particularly for the interpretation of the clinical presentation of HA
      patients. 

PMID- 25377323
TI  - Natural history of thrombotic thrombocytopenic purpura and hemolytic uremic
      syndrome.
AB  - The differential diagnosis of thrombotic microangiopathy (TMA) has become clearer
      following the establishment of the relationships between (1) diarrhea-associated
      hemolytic uremic syndrome (HUS) and Shiga toxin-producing Escherichia coli-HUS
      (STEC-HUS), (2) a markedly reduced ADAMTS-13 (a disintegrin and metalloproteinase
      with a thrombospondin type 1 motif, member 13) level and typical thrombotic
      thrombocytopenic purpura (TTP), and (3) abnormalities in the complement
      regulatory system and atypical HUS (aHUS). These TMAs include typical TTP, other
      forms of TMA, STEC-HUS, and aHUS. The pathological mechanisms of TMA still
      overlap among several forms of TMA. With respect to the management of TMA, the
      use of plasma exchange (PE) for typical TTP, additional steroid therapy for TMA
      and rituximab for typical TTP with a high titer of the inhibitor of ADAMTS-13, as
      well as eculizumab for aHUS, have also been established. Although several issues
      remain in the pathophysiology and management of TMA, new findings will hopefully
      resolve these problems in the near future. 

PMID- 25377324
TI  - Cause-specific mortality in Africa and Asia: evidence from INDEPTH health and
      demographic surveillance system sites.
AB  - BACKGROUND: Because most deaths in Africa and Asia are not well documented,
      estimates of mortality are often made using scanty data. The INDEPTH Network
      works to alleviate this problem by collating detailed individual data from
      defined Health and Demographic Surveillance sites. By registering all deaths over
      time and carrying out verbal autopsies to determine cause of death across many
      such sites, using standardised methods, the Network seeks to generate population
      based mortality statistics that are not otherwise available. OBJECTIVE: To build
      a large standardised mortality database from African and Asian sites, detailing
      the relevant methods, and use it to describe cause-specific mortality patterns.
      DESIGN: Individual demographic and verbal autopsy (VA) data from 22 INDEPTH sites
      were collated into a standardised database. The INDEPTH 2013 population was used
      for standardisation. The WHO 2012 VA standard and the InterVA-4 model were used
      for assigning cause of death. RESULTS: A total of 111,910 deaths occurring over
      12,204,043 person-years (accumulated between 1992 and 2012) were registered
      across the 22 sites, and for 98,429 of these deaths (88.0%) verbal autopsies were
      successfully completed. There was considerable variation in all-cause mortality
      between sites, with most of the differences being accounted for by variations in
      infectious causes as a proportion of all deaths. CONCLUSIONS: This dataset
      documents individual deaths across Africa and Asia in a standardised way, and on
      an unprecedented scale. While INDEPTH sites are not constructed to constitute a
      representative sample, and VA may not be the ideal method of determining cause of
      death, nevertheless these findings represent detailed mortality patterns for
      parts of the world that are severely under-served in terms of measuring
      mortality. Further papers explore details of mortality patterns among children
      and specifically for NCDs, external causes, pregnancy-related mortality, malaria,
      and HIV/AIDS. Comparisons will also be made where possible with other findings on
      mortality in the same regions. Findings presented here and in accompanying papers
      support the need for continued work towards much wider implementation of
      universal civil registration of deaths by cause on a worldwide basis.

PMID- 25377325
TI  - Cause-specific childhood mortality in Africa and Asia: evidence from INDEPTH
      health and demographic surveillance system sites.
AB  - BACKGROUND: Childhood mortality, particularly in the first 5 years of life, is a
      major global concern and the target of Millennium Development Goal 4. Although
      the majority of childhood deaths occur in Africa and Asia, these are also the
      regions where such deaths are least likely to be registered. The INDEPTH Network
      works to alleviate this problem by collating detailed individual data from
      defined Health and Demographic Surveillance sites. By registering deaths and
      carrying out verbal autopsies to determine cause of death across many such sites,
      using standardised methods, the Network seeks to generate population-based
      mortality statistics that are not otherwise available. OBJECTIVE: To present a
      description of cause-specific mortality rates and fractions over the first 15
      years of life as documented by INDEPTH Network sites in sub-Saharan Africa and
      south-east Asia. DESIGN: All childhood deaths at INDEPTH sites are routinely
      registered and followed up with verbal autopsy (VA) interviews. For this study,
      VA archives were transformed into the WHO 2012 VA standard format and processed
      using the InterVA-4 model to assign cause of death. Routine surveillance data
      also provided person-time denominators for mortality rates. Cause-specific
      mortality rates and cause-specific mortality fractions are presented according to
      WHO 2012 VA cause groups for neonatal, infant, 1-4 year and 5-14 year age groups.
      RESULTS: A total of 28,751 childhood deaths were documented during 4,387,824
      person-years over 18 sites. Infant mortality ranged from 11 to 78 per 1,000 live
      births, with under-5 mortality from 15 to 152 per 1,000 live births. Sites in
      Vietnam and Kenya accounted for the lowest and highest mortality rates reported.
      CONCLUSIONS: Many children continue to die from relatively preventable causes,
      particularly in areas with high rates of malaria and HIV/AIDS. Neonatal mortality
      persists at relatively high, and perhaps sometimes under-documented, rates.
      External causes of death are a significant childhood problem in some settings.

PMID- 25377326
TI  - Adult non-communicable disease mortality in Africa and Asia: evidence from
      INDEPTH Health and Demographic Surveillance System sites.
AB  - BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global
      issue, as other categories of mortality have diminished and life expectancy has
      increased. The World Health Organization's Member States have called for a 25%
      reduction in premature NCD mortality by 2025, which can only be achieved by
      substantial reductions in risk factors and improvements in the management of
      chronic conditions. A high burden of NCD mortality among much older people, who
      have survived other hazards, is inevitable. The INDEPTH Network collects detailed
      individual data within defined Health and Demographic Surveillance sites. By
      registering deaths and carrying out verbal autopsies to determine cause of death
      across many such sites, using standardised methods, the Network seeks to generate
      population-based mortality statistics that are not otherwise available.
      OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites
      across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause
      categories, with separate consideration of premature (15-64 years) and older (65+
      years) NCD mortality. DESIGN: All adult deaths at INDEPTH sites are routinely
      registered and followed up with VA interviews. For this study, VA archives were
      transformed into the WHO 2012 VA standard format and processed using the InterVA
      4 model to assign cause of death. Routine surveillance data also provide person
      time denominators for mortality rates. RESULTS: A total of 80,726 adult (over 15
      years) deaths were documented over 7,423,497 person-years of observation. NCDs
      were attributed as the cause for 35.6% of these deaths. Slightly less than half
      of adult NCD deaths occurred in the 15-64 age group. Detailed results are
      presented by age and sex for leading causes of NCD mortality. Per-site rates of
      NCD mortality were significantly correlated with rates of HIV/AIDS-related
      mortality. CONCLUSIONS: These findings present important evidence on the
      distribution of NCD mortality across a wide range of African and Asian settings.
      This comes against a background of global concern about the burden of NCD
      mortality, especially among adults aged under 70, and provides an important
      baseline for future work.

PMID- 25377327
TI  - Mortality from external causes in Africa and Asia: evidence from INDEPTH Health
      and Demographic Surveillance System Sites.
AB  - BACKGROUND: Mortality from external causes, of all kinds, is an important
      component of overall mortality on a global basis. However, these deaths, like
      others in Africa and Asia, are often not counted or documented on an individual
      basis. Overviews of the state of external cause mortality in Africa and Asia are
      therefore based on uncertain information. The INDEPTH Network maintains
      longitudinal surveillance, including cause of death, at population sites across
      Africa and Asia, which offers important opportunities to document external cause
      mortality at the population level across a range of settings. OBJECTIVE: To
      describe patterns of mortality from external causes at INDEPTH Network sites
      across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause
      categories. DESIGN: All deaths at INDEPTH sites are routinely registered and
      followed up with VA interviews. For this study, VA archives were transformed into
      the WHO 2012 VA standard format and processed using the InterVA-4 model to assign
      cause of death. Routine surveillance data also provide person-time denominators
      for mortality rates. RESULTS: A total of 5,884 deaths due to external causes were
      documented over 11,828,253 person-years. Approximately one-quarter of those
      deaths were to children younger than 15 years. Causes of death were dominated by
      childhood drowning in Bangladesh, and by transport-related deaths and intentional
      injuries elsewhere. Detailed mortality rates are presented by cause of death, age
      group, and sex. CONCLUSIONS: The patterns of external cause mortality found here
      generally corresponded with expectations and other sources of information, but
      they fill some important gaps in population-based mortality data. They provide an
      important source of information to inform potentially preventive intervention
      designs.

PMID- 25377328
TI  - Pregnancy-related mortality in Africa and Asia: evidence from INDEPTH Health and
      Demographic Surveillance System sites.
AB  - BACKGROUND: Women continue to die in unacceptably large numbers around the world
      as a result of pregnancy, particularly in sub-Saharan Africa and Asia. Part of
      the problem is a lack of accurate, population-based information characterising
      the issues and informing solutions. Population surveillance sites, such as those
      operated within the INDEPTH Network, have the potential to contribute to bridging
      the information gaps. OBJECTIVE: To describe patterns of pregnancy-related
      mortality at INDEPTH Network Health and Demographic Surveillance System sites in
      sub-Saharan Africa and southeast Asia in terms of maternal mortality ratio (MMR)
      and cause-specific mortality rates. DESIGN: Data on individual deaths among women
      of reproductive age (WRA) (15-49) resident in INDEPTH sites were collated into a
      standardised database using the INDEPTH 2013 population standard, the WHO 2012
      verbal autopsy (VA) standard, and the InterVA model for assigning cause of death.
      RESULTS: These analyses are based on reports from 14 INDEPTH sites, covering
      14,198 deaths among WRA over 2,595,605 person-years observed. MMRs varied between
      128 and 461 per 100,000 live births, while maternal mortality rates ranged from
      0.11 to 0.74 per 1,000 person-years. Detailed rates per cause are tabulated,
      including analyses of direct maternal, indirect maternal, and incidental
      pregnancy-related deaths across the 14 sites. CONCLUSIONS: As expected, these
      findings confirmed unacceptably high continuing levels of maternal mortality.
      However, they also demonstrate the effectiveness of INDEPTH sites and of the VA
      methods applied to arrive at measurements of maternal mortality that are
      essential for planning effective solutions and monitoring programmatic impacts.

PMID- 25377331
TI  - Cause-specific mortality and socioeconomic status in Chakaria, Bangladesh.
AB  - BACKGROUND: Bangladesh has achieved remarkable gains in health indicators during
      the last four decades despite low levels of economic development. However, the
      persistence of inequities remains disturbing. This success was also accompanied
      by health and demographic transitions, which in turn brings new challenges for a
      nation that has yet to come to terms with pre-transition health challenges. It is
      therefore important to understand the causes of death and their relationship with
      socioeconomic status (SES). OBJECTIVE: The paper aims to assess the causes of
      death by SES based on surveillance data from a rural area of Bangladesh, in order
      to understand the situation and inform policy makers and programme leaders.
      DESIGN: We analysed population-based mortality data collected from the Chakaria
      Health and Demographic Surveillance System in Bangladesh. The causes of death
      were determined by using a Bayesian-based programme for interpreting verbal
      autopsy findings (InterVA-4). The data included 1,391 deaths in 217,167 person
      years of observation between 2010 and 2012. The wealth index constructed using
      household assets was used to assess the SES, and disease burdens were compared
      among the wealth quintiles. RESULTS: Analysing cause of death (CoD) revealed that
      non-communicable diseases (NCDs) were the leading causes of deaths (37%),
      followed by communicable diseases (CDs) (22%), perinatal and neonatal conditions
      (11%), and injury and accidents (6%); the cause of remaining 24% of deaths could
      not be determined. Age-specific mortality showed premature birth, respiratory
      infections, and drowning were the dominant causes of death for childhood
      mortality (0-14 years), which was inversely associated with SES (p<0.04). For
      adult and the elderly (15 years and older), NCDs were the leading cause of death
      (51%), followed by CDs (23%). For adult and the elderly, NCDs concentrated among
      the population from higher SES groups (p<0.005), and CDs among the lower SES
      groups (p<0.001). CONCLUSIONS: Epidemiologic transition is taking place with a
      shift from the dominance of CDs to NCDs. SES inequity in mortality still persists
      -the poor suffer from CDs in all age groups, whereas those better off suffer more
      from NCDs than CDs. Policy makers thus need to consider the social distribution
      of diseases before developing any public health action targeted towards reducing
      mortality and the extent of disease burden in an equitable manner.

PMID- 25377329
TI  - Malaria mortality in Africa and Asia: evidence from INDEPTH health and
      demographic surveillance system sites.
AB  - BACKGROUND: Malaria continues to be a major cause of infectious disease mortality
      in tropical regions. However, deaths from malaria are most often not individually
      documented, and as a result overall understanding of malaria epidemiology is
      inadequate. INDEPTH Network members maintain population surveillance in Health
      and Demographic Surveillance System sites across Africa and Asia, in which
      individual deaths are followed up with verbal autopsies. OBJECTIVE: To present
      patterns of malaria mortality determined by verbal autopsy from INDEPTH sites
      across Africa and Asia, comparing these findings with other relevant information
      on malaria in the same regions. DESIGN: From a database covering 111,910 deaths
      over 12,204,043 person-years in 22 sites, in which verbal autopsy data were
      handled according to the WHO 2012 standard and processed using the InterVA-4
      model, over 6,000 deaths were attributed to malaria. The overall period covered
      was 1992-2012, but two-thirds of the observations related to 2006-2012. These
      deaths were analysed by site, time period, age group and sex to investigate
      epidemiological differences in malaria mortality. RESULTS: Rates of malaria
      mortality varied by 1:10,000 across the sites, with generally low rates in Asia
      (one site recording no malaria deaths over 0.5 million person-years) and some of
      the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person
      years). Childhood malaria mortality rates were strongly correlated with Malaria
      Atlas Project estimates of Plasmodium falciparum parasite rates for the same
      locations. Adult malaria mortality rates, while lower than corresponding
      childhood rates, were strongly correlated with childhood rates at the site level.
      CONCLUSIONS: The wide variations observed in malaria mortality, which were
      nevertheless consistent with various other estimates, suggest that population
      based registration of deaths using verbal autopsy is a useful approach to
      understanding the details of malaria epidemiology.

PMID- 25377332
TI  - Who died of what in rural KwaZulu-Natal, South Africa: a cause of death analysis
      using InterVA-4.
AB  - BACKGROUND: For public health purposes, it is important to see whether men and
      women in different age groups die of the same causes in South Africa. OBJECTIVE:
      We explored sex- and age-specific patterns of causes of deaths in a rural
      demographic surveillance site in northern KwaZulu-Natal in South Africa over the
      period 2000-2011. DESIGN: Deaths reported through the demographic surveillance
      were followed up by a verbal autopsy (VA) interview using a standardised
      questionnaire. Causes of death were assigned likelihoods using the publicly
      available tool InterVA-4. Cause-specific mortality fractions were determined by
      age and sex. RESULTS: Over the study period, a total of 5,416 (47%) and 6,081
      (53%) deaths were recorded in men and women, respectively. Major causes of death
      proportionally affecting more women than men were (all p<0.0001): human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (20.1% vs.
      13.6%), other and unspecified cardiac disease (5.9% vs. 3.2%), stroke (4.5% vs.
      2.7%), reproductive neoplasms (1.7% vs. 0.4%), diabetes (2.4% vs. 1.2%), and
      breast neoplasms (0.4% vs. 0%). Major causes of deaths proportionally affecting
      more men than women were (all p<0.0001) assault (6.1% vs. 1.7%), pulmonary
      tuberculosis (34.5% vs. 30.2%), road traffic accidents (3.0% vs. 1.0%),
      intentional self-harm (1.3% vs. 0.3%), and respiratory neoplasms (2.5% vs. 1.5%).
      Causes of death due to communicable diseases predominated in all age groups
      except in older persons. CONCLUSIONS: While mortality during the 2000s was
      dominated by tuberculosis and HIV/AIDS, we found substantial sex-specific
      differences both for communicable and non-communicable causes of death, some
      which can be explained by a differing sex-specific age structure. InterVA-4 is
      likely to be a valuable tool for investigating causes of death patterns in other
      similar Southern African settings.

PMID- 25377330
TI  - HIV/AIDS-related mortality in Africa and Asia: evidence from INDEPTH health and
      demographic surveillance system sites.
AB  - BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has
      been the most affected region, even though a large proportion of HIV/AIDS deaths
      have not been documented at the individual level. Systematic application of
      verbal autopsy (VA) methods in defined populations provides an opportunity to
      assess the mortality burden of the pandemic from individual data. OBJECTIVE: To
      present standardised comparisons of HIV/AIDS-related mortality at sites across
      Africa and Asia, including closely related causes of death such as pulmonary
      tuberculosis (PTB) and pneumonia. DESIGN: Deaths related to HIV/AIDS were
      extracted from individual demographic and VA data from 22 INDEPTH sites across
      Africa and Asia. VA data were standardised to WHO 2012 standard causes of death
      assigned using the InterVA-4 model. Between-site comparisons of mortality rates
      were standardised using the INDEPTH 2013 standard population. RESULTS: The
      dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over
      12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates
      varied widely across Africa and Asia, with highest burdens in eastern and
      southern Africa, and lowest burdens in Asia. There was evidence of rapidly
      declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was
      also strongly related to PTB mortality. On a country basis, there were strong
      similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived
      from modelled estimates. CONCLUSIONS: Measuring HIV/AIDS-related mortality
      continues to be a challenging issue, all the more so as anti-retroviral treatment
      programmes alleviate mortality risks. The congruence between these results and
      other estimates adds plausibility to both approaches. These data, covering some
      of the highest mortality observed during the pandemic, will be an important
      baseline for understanding the future decline of HIV/AIDS.

PMID- 25377333
TI  - Distribution of cause of death in rural Bangladesh during 2003-2010: evidence
      from two rural areas within Matlab Health and Demographic Surveillance site.
AB  - OBJECTIVE: This study used the InterVA-4 computerised model to assign probable
      cause of death (CoD) to verbal autopsies (VAs) generated from two rural areas,
      with a difference in health service provision, within the Matlab Health and
      Demographic Surveillance site (HDSS). This study aimed to compare CoD by gender,
      as well as discussing possible factors which could influence differences in the
      distribution of CoD between the two areas. DESIGN: Data for this study came from
      the Matlab the HDSS maintained by the International Centre for Diarrhoeal Disease
      Research, Bangladesh (icddr,b) since 1966. In late 1977, icddr,b divided HDSS and
      implemented a high-quality maternal, newborn and child health and family planning
      (MNCH-FP) services project in one half, called the icddr,b service area (SA), in
      addition to the usual public and private MNCH-FP services that serve the other
      half, called the government SA. HDSS field workers registered 12,144 deaths
      during 2003-2010, and trained interviewers obtained VA for 98.9% of them. The
      probabilistic model InterVA-4 probabilistic model (version 4.02) was used to
      derive probable CoD from VA symptoms. Cause-specific mortality rates and
      fractions were compared across gender and areas. Appropriate statistical tests
      were applied for significance testing. RESULTS: Mortality rates due to neonatal
      causes and communicable diseases (CDs) were lower in the icddr,b SA than in the
      government SA, where mortality rates due to non-communicable diseases (NCDs) were
      lower. Cause-specific mortality fractions (CSMFs) due to CDs (23.2% versus 18.8%)
      and neonatal causes (7.4% versus 6%) were higher in the government SA, whereas
      CSMFs due to NCDs were higher (58.2% versus 50.7%) in the icddr,b SA. The rank
      order of CSMFs by age group showed marked variations, the largest category being
      acute respiratory infection/pneumonia in infancy, injury in 1-4 and 5-14 years,
      neoplasms in 15-49 and 50-64 years, and stroke in 65+ years. CONCLUSIONS:
      Automated InterVA-4 coding of VA to determine probable CoD revealed the
      difference in the structure of CoD between areas with prominence of NCDs in both
      areas. Such information can help local planning of health services for prevention
      and management of disease burden.

PMID- 25377334
TI  - Causes of death in two rural demographic surveillance sites in Bangladesh, 2004
      2010: automated coding of verbal autopsies using InterVA-4.
AB  - OBJECTIVE: Population-based information on causes of death (CoD) by age, sex, and
      area is critical for countries with limited resources to identify and address key
      public health issues. This study analysed the demographic surveillance and verbal
      autopsy (VA) data to estimate age- and sex-specific mortality rates and cause
      specific mortality fractions in two well-defined rural populations within the
      demographic surveillance system in Abhoynagar and Mirsarai subdistricts, located
      in different climatic zones. DESIGN: During 2004-2010, the sample demographic
      surveillance system registered 1,384 deaths in Abhoynagar and 1,847 deaths in
      Mirsarai. Trained interviewers interviewed the main caretaker of the deceased
      with standard VA questionnaires to record signs and symptoms of diseases or
      conditions that led to death and health care experiences before death. The
      computer-automated InterVA-4 method was used to analyse VAs to determine probable
      CoD. RESULTS: Age- and sex-specific death rates revealed a higher neonatal
      mortality rate in Abhoynagar than Mirsarai, and death rates and sex ratios of
      male to female death rates were higher in the ages after infancy. Communicable
      diseases (CDs) accounted for 16.7% of all deaths in Abhoynagar and 21.2% in
      Mirsarai--the difference was due mostly to more deaths from acute respiratory
      infections, pneumonia, and tuberculosis in Mirsarai. Non-communicable diseases
      (NCDs) accounted for 56.2 and 55.3% of deaths in each subdistrict, respectively,
      with leading causes being stroke (16.5-19.3%), neoplasms (13.2% each), cardiac
      diseases (8.9-11.6%), chronic obstructive pulmonary diseases (5.1-6.3%), diseases
      of the digestive system (3.1-4.1%), and diabetes (2.8-3.5%), together accounting
      for 49.2-51.2% points of the NCD deaths in the two subdistricts. Injury and other
      external causes accounted for another 7.5-7.7% deaths, with self-harm being
      higher among females in Abhoynagar. CONCLUSIONS: The computer-automated coding of
      VA to determine CoD reconfirmed that NCDs were the leading CoD with some
      differences between the sites. Incorporating VA into the national sample vital
      registration system can help policy makers to identify the leading CoDs for
      public health planning.

PMID- 25377335
TI  - Comparing causes of death between formal and informal neighborhoods in urban
      Africa: evidence from Ouagadougou Health and Demographic Surveillance System.
AB  - BACKGROUND: The probable coexistence of two or more epidemiological profiles in
      urban Africa is poorly documented. In particular, very few studies have focused
      on the comparison of cause-specific mortality between two types of neighborhoods
      that characterize contemporary southern cities: formal neighborhoods, that is,
      structured or delineated settlements (planned estates) that have full access to
      public utilities (electricity and water services), and the informal
      neighborhoods, that is, spontaneous and unplanned peri-urban settlements where
      people live in slum-like conditions, often with little or no access to public
      utilities. OBJECTIVE: To compare the causes of death between the formal and
      informal neighborhoods covered by the Ouagadougou Health and Demographic
      Surveillance Systems (HDSS). DESIGN: The data used come from the INDEPTH pooled
      dataset which includes the contribution of Ouagadougou HDSS and are compiled for
      the INDEPTH Network Data repository. The data were collected between 2009 and
      2011 using verbal autopsy (VA) questionnaires completed by four fieldworkers well
      trained in the conduction of VAs. The VA data were then interpreted using the
      InterVA-4 program (version 4.02) to arrive at the causes of death. RESULTS:
      Communicable diseases are the leading cause of death among children (aged between
      29 days and 14 years) in both formal and informal neighborhoods, contributing
      more than 75% to the mortality rate. Mortality rates from non-communicable
      diseases (NCDs) are very low before age 15 but are the leading causes from age
      50, especially in formal neighborhoods. Mortality from injuries is very low, with
      no significant difference between the two neighborhoods. CONCLUSIONS: The fact
      that mortality from NCDs is higher among adults in formal neighborhoods seems
      consistent with the idea of a correlation between modern life and epidemiological
      transition. However, NCDs do affect informal neighborhoods as well. They consist
      mainly of cardiovascular diseases and neoplasms most of which are preventable
      and/or manageable through a change in lifestyle. A prevention program would
      certainly reduce the burden of these chronic diseases among adults and the
      elderly with a significant economic impact for families.

PMID- 25377336
TI  - Trends in non-communicable disease mortality among adult residents in Nairobi's
      slums, 2003-2011: applying InterVA-4 to verbal autopsy data.
AB  - BACKGROUND: About 80% of deaths from non-communicable diseases (NCDs) occur in
      developing countries such as Kenya. However, not much is known about the burden
      of NCDs in slums, which account for about 60% of the residences of the urban
      population in Kenya. This study examines trends in NCD mortality from two slum
      settings in Nairobi. DESIGN: We use verbal autopsy data on 1954 deaths among
      adults aged 35 years and older who were registered in the Nairobi Urban Health
      and Demographic Surveillance System between 2003 and 2011. InterVA-4, a computer
      based program, was used to assign causes of death for each case. RESULTS are
      presented as annualized cause-specific mortality rates (CSMRs) and cause-specific
      mortality fractions (CSMFs) by sex. RESULTS: The CSMRs for NCDs did not appear to
      change significantly over time for both males and females. Among males,
      cardiovascular diseases (CVDs) and neoplasms were the leading NCDs--contributing
      CSMFs of 8 and 5%, respectively, on average over time. Among females, CVDs
      contributed a CSMF of 14% on average over time, while neoplasms contributed 8%.
      Communicable diseases and related conditions remained the leading causes of
      death, contributing a CSMF of over 50% on average in males and females over time.
      CONCLUSIONS: Our findings are consistent with the Global Burden of Disease 2010
      study which shows that communicable diseases remain the dominant cause of death
      in Africa, although NCDs were still significant contributors to mortality. We
      recommend an integrated approach towards disease prevention that focuses on
      health systems strengthening in resource-limited settings such as slums.

PMID- 25377337
TI  - Estimating cause of adult (15+ years) death using InterVA-4 in a rural district
      of southern Ghana.
AB  - BACKGROUND: Data needed to estimate causes of death and the pattern of these
      deaths are scarce in sub-Saharan Africa. Such data are very important for
      targeting, monitoring, and evaluating health interventions. OBJECTIVE: To
      estimate the mortality rate and determine causes of death among adults (aged 15
      years and older) in a rural district of southern Ghana, using the InterVA-4
      model. DESIGN: Data used were generated from verbal autopsies conducted for
      registered adult members of the Dodowa Health and Demographic Surveillance System
      who died between 2006 and 2010. The InterVA-4 model was used to assign the cause
      of death. RESULTS: Overall, the mortality rate for the period under review was
      7.5/1,000 person-years (py) for the general population and 10.4/1,000 py for
      those aged 15 and older. The leading cause of death was communicable diseases
      (CDs), with a malaria-specific mortality rate of 1.06/1,000 py. Pulmonary
      tuberculosis (TB)-specific mortality rate was the next highest (1.01/1,000 py).
      HIV/AIDS attributed deaths were lower among males than females. Non-communicable
      diseases (NCDs) contributed to 28.3% of the deaths with cause-specific mortality
      rate of 2.93/1,000 py. Stroke topped the list with cause-specific mortality rate
      of 0.69/1,000 py. As expected, young males (15-49 years) contributed to more road
      traffic accident (RTA) deaths; they had a lower RTA cause-specific mortality rate
      than older males (50-64 years). CONCLUSIONS: Data indicate that CDs (e.g. malaria
      and TB) remain the major cause of death with NCDs (e.g. stroke) following closely
      behind. Verbal autopsy data can provide the causes of mortality in poorly
      resourced settings where access to timely and accurate data is scarce.

PMID- 25377338
TI  - Applying the InterVA-4 model to determine causes of death in rural Ethiopia.
AB  - BACKGROUND: In Ethiopia, most deaths take place at home and routine certification
      of cause of death by physicians is lacking. As a result, reliable cause of death
      (CoD) data are often not available. Recently, a computerized method for
      interpretation of verbal autopsy (VA) data, called InterVA, has been developed
      and used. It calculates the probability of a set of CoD given the presence of
      circumstances, signs, and symptoms reported during VA interviews. We applied the
      InterVA model to describe CoD in a rural population of Ethiopia. OBJECTIVE: VA
      data for 436/599 (72.7%) deaths that occurred during 2010-2011 were included.
      InterVA-4 was used to interpret the VA data into probable cause of death. Cause
      specific mortality fraction was used to describe frequency of occurrence of death
      from specific causes. RESULTS: InterVA-4 was able to give likely cause(s) of
      death for 401/436 of the cases (92.0%). Overall, 35.0% of the total deaths were
      attributed to communicable diseases, and 30.7% to chronic non-communicable
      diseases. Tuberculosis (12.5%) and acute respiratory tract infections (10.4%)
      were the most frequent causes followed by neoplasms (9.6%) and diseases of
      circulatory system (7.2%). CONCLUSION: InterVA-4 can produce plausible estimates
      of the major public health problems that can guide public health interventions.
      We encourage further validation studies, in local settings, so that InterVA can
      be integrated into national health surveys.

PMID- 25377339
TI  - Cause of death during 2009-2012, using a probabilistic model (InterVA-4): an
      experience from Ballabgarh Health and Demographic Surveillance System in India.
AB  - OBJECTIVES: The present study aimed to estimate the age and cause-specific
      mortality in Ballabgarh Health and Demographic Surveillance System (HDSS) site
      for the years 2009 to 2012, using a probabilistic model (InterVA-4). METHODS: All
      Deaths in Ballabgarh HDSS from January 1, 2009, to December 31, 2012, were
      included in the study. InterVA-4 model (version 4.02) was used for assigning
      cause of death (COD). Data from the verbal autopsy (VA) tool were extracted and
      processed with the InterVA-4 model. Cause-specific mortality rate (CSMR) per
      1,000 person-years was calculated. RESULTS: A total of 2,459 deaths occurred in
      the HDSS during the year 2009 to 2012. Among them, 2,174 (88.4%) valid VA
      interviews were conducted. Crude death rate ranged from 7.1 (2009) to 6.4 (2012)
      per 1,000 population. The CSMR per 1,000 person-years over the years (2009-2012)
      for non-communicable diseases, communicable diseases, trauma, neoplasm, and
      maternal and neonatal diseases were 1.78, 1.68, 0.68, 0.49, and 0.48,
      respectively. The most common causes of death among children, adults, and the
      elderly were infectious diseases, trauma, and non-communicable diseases,
      respectively. CONCLUSIONS: Overall, non-communicable diseases constituted the
      largest proportion of mortality, whereas trauma was the most common COD among
      adults at Ballabgarh HDSS. Policy-makers ought to focus on prevention of
      premature CODs, especially prevention of infectious diseases in children, and
      intentional self-harm and road traffic accidents in the adult population.

PMID- 25377340
TI  - Childhood cause-specific mortality in rural Western Kenya: application of the
      InterVA-4 model.
AB  - BACKGROUND: Assessing the progress in achieving the United Nation's Millennium
      Development Goals in terms of population health requires consistent and reliable
      information on cause-specific mortality, which is often rare in resource
      constrained countries. Health and demographic surveillance systems (HDSS) have
      largely used medical personnel to review and assign likely causes of death based
      on the information gathered from standardized verbal autopsy (VA) forms. However,
      this approach is expensive and time consuming, and it may lead to biased results
      based on the knowledge and experience of individual clinicians. We assessed the
      cause-specific mortality for children under 5 years old (under-5 deaths) in Siaya
      County, obtained from a computer-based probabilistic model (InterVA-4). DESIGN:
      Successfully completed VA interviews for under-5 deaths conducted between January
      2003 and December 2010 in the Kenya Medical Research Institute/US Centers for
      Disease Control and Prevention HDSS were extracted from the VA database and
      processed using the InterVA-4 (version 4.02) model for interpretation. Cause
      specific mortality fractions were then generated from the causes of death
      produced by the model. RESULTS: A total of 84.33% (6,621) childhood deaths had
      completed VA data during the study period. Children aged 1-4 years constituted
      48.53% of all cases, and 42.50% were from infants. A single cause of death was
      assigned to 89.18% (5,940) of cases, 8.35% (556) of cases were assigned two
      causes, and 2.10% (140) were assigned 'indeterminate' as cause of death by the
      InterVA-4 model. Overall, malaria (28.20%) was the leading cause of death,
      followed by acute respiratory infection including pneumonia (25.10%), in under-5
      children over the study period. But in the first 5 years of the study period,
      acute respiratory infection including pneumonia was the main cause of death,
      followed by malaria. Similar trends were also reported in infants (29 days-11
      months) and children aged 1-4 years. CONCLUSIONS: Under-5 cause-specific
      mortality obtained using the InterVA-4 model is consistent with existing
      knowledge on the burden of childhood diseases in rural western Kenya.

PMID- 25377341
TI  - Cause-specific mortality at INDEPTH Health and Demographic Surveillance System
      Sites in Africa and Asia: concluding synthesis.
AB  - This synthesis brings together findings on cause-specific mortality documented by
      means of verbal autopsies applied to over 110,000 deaths across Africa and Asia,
      within INDEPTH Network sites. METHODS: Developments in computerised methods to
      assign causes of death on the basis of data from verbal autopsy (VA) interviews
      have made possible these standardised analyses of over 110,000 deaths from 22
      African and Asian Health and Demographic Surveillance System sites in the INDEPTH
      Network. In addition to previous validations of the InterVA-4 probabilistic
      model, these wide-ranging analyses provide further evidence of the applicability
      of this approach to assigning the cause of death. Plausible comparisons with
      existing knowledge of disease patterns, as well as substantial correlations with
      out-of-model parameters such as time period, country, and other independent data
      sources were observed. FINDINGS: Substantial variations in mortality between
      sites, and in some cases within countries, were observed. A number of the
      mortality burdens revealed clearly constitute grounds for public health actions.
      At an overall level, these included high maternal and neonatal mortality rates.
      More specific examples were childhood drowning in Bangladesh and homicide among
      adult males in eastern and southern Africa. Mortality from non-communicable
      diseases, particularly in younger adulthood, is an emerging cause for concern.
      INDEPTH's approach of documenting all deaths in particular populations, and
      successfully assigning causes to the majority, is important for formulating
      health policies. FUTURE DIRECTIONS: The pooled dataset underlying these analyses
      is available at the INDEPTH Data Repository for further analysis. INDEPTH will
      continue to fill cause-specific mortality knowledge gaps across Africa and Asia,
      which will also serve as a baseline for post-2015 development goals. The more
      widespread use of similar VA methods within routine civil registration systems is
      likely to become an important medium-term strategy in many countries.

PMID- 25377342
TI  - Causes of death among persons of all ages within the Kilifi Health and
      Demographic Surveillance System, Kenya, determined from verbal autopsies
      interpreted using the InterVA-4 model.
AB  - BACKGROUND: The vast majority of deaths in the Kilifi study area are not recorded
      through official systems of vital registration. As a result, few data are
      available regarding causes of death in this population. OBJECTIVE: To describe
      the causes of death (CODs) among residents of all ages within the Kilifi Health
      and Demographic Surveillance System (KHDSS) on the coast of Kenya. DESIGN: Verbal
      autopsies (VAs) were conducted using the 2007 World Health Organization (WHO)
      standard VA questionnaires, and VA data further transformed to align with the
      2012 WHO VA instrument. CODs were then determined using the InterVA-4 computer
      based probabilistic model. RESULTS: Five thousand one hundred and eighty seven
      deaths were recorded between January 2008 and December 2011. VA interviews were
      completed for 4,460 (86%) deaths. Neonatal pneumonia and birth asphyxia were the
      main CODs in neonates; pneumonia and malaria were the main CODs among infants and
      children aged 1-4, respectively, while HIV/AIDS was the main COD for adult women
      of reproductive age. Road traffic accidents were more commonly observed among men
      than women. Stroke and neoplasms were common CODs among the elderly over the age
      of 65. CONCLUSIONS: We have established the main CODs among people of all ages
      within the area served by the KHDSS on the coast of Kenya using the 2007 WHO VA
      questionnaire coded using InterVA-4. We hope that our data will allow local
      health planners to estimate the burden of various diseases and to allocate their
      limited resources more appropriately.

PMID- 25377343
TI  - Two decades of mortality change in rural northeast South Africa.
AB  - BACKGROUND: The MRC/Wits University Agincourt research centre, part of the
      INDEPTH Network, has documented mortality in a defined population in the rural
      northeast of South Africa for 20 years (1992-2011) using long-term health and
      socio-demographic surveillance. Detail on the unfolding, at times unpredicted,
      mortality pattern has been published. This experience is reviewed here and
      updated using more recent data. OBJECTIVE: To present a review and summary of
      mortality patterns across all age-sex groups in the Agincourt sub-district
      population for the period 1992-2011 as a comprehensive basis for public health
      action. DESIGN: Vital events in the Agincourt population have been updated in
      annual surveys undertaken since 1992. All deaths have been rigorously recorded
      and followed by verbal autopsy interviews. Responses to questions from these
      interviews have been processed retrospectively using the WHO 2012 verbal autopsy
      standard and the InterVA-4 model for assigning causes of death in a standardised
      manner. RESULTS: Between 1992 and 2011, a total of 12,209 deaths were registered
      over 1,436,195 person-years of follow-up, giving a crude mortality rate of 8.5
      per 1,000 person-years. During the 20-year period, the population experienced a
      major HIV epidemic, which resulted in more than doubling of overall mortality for
      an extended period. Recent years show signs of declining mortality, but levels
      remain above the 1992 baseline recorded using the surveillance system.
      CONCLUSIONS: The Agincourt population has experienced a major mortality shock
      over the past two decades from which it will take time to recover. The basic
      epidemic patterns are consistent with generalised mortality patterns observed in
      South Africa as a whole, but the detailed individual surveillance behind these
      analyses allows finer-grained analyses of specific causes, age-related risks, and
      trends over time. These demonstrate the complex, somewhat unpredicted course of
      mortality transition over the years since the dawn of South Africa's democratic
      era in 1994.

PMID- 25377344
TI  - Disease-specific mortality burdens in a rural Gambian population using verbal
      autopsy, 1998-2007.
AB  - OBJECTIVE: To estimate and evaluate the cause-of-death structure and disease
      specific mortality rates in a rural area of The Gambia as determined using the
      InterVA-4 model. DESIGN: Deaths and person-years of observation were determined
      by age group for the population of the Farafenni Health and Demographic
      Surveillance area from January 1998 to December 2007. Causes of death were
      determined by verbal autopsy (VA) using the InterVA-4 model and ICD-10 disease
      classification. Assigned causes of death were classified into six broad groups:
      infectious and parasitic diseases; cancers; other non-communicable diseases;
      neonatal; maternal; and external causes. Poisson regression was used to estimate
      age and disease-specific mortality rates, and likelihood ratio tests were used to
      determine statistical significance. RESULTS: A total of 3,203 deaths were
      recorded and VA administered for 2,275 (71%). All-age mortality declined from 15
      per 1,000 person-years in 1998-2001 to 8 per 1,000 person-years in 2005-2007.
      Children aged 1-4 years registered the most marked (74%) decline from 27 to 7 per
      1,000 person-years. Communicable diseases accounted for half (49.9%) of the
      deaths in all age groups, dominated by acute respiratory infections (ARI)
      (13.7%), malaria (12.9%) and pulmonary tuberculosis (10.2%). The leading causes
      of death among infants were ARI (5.59 per 1,000 person-years [95% CI: 4.38-7.15])
      and malaria (4.11 per 1,000 person-years [95% CI: 3.09-5.47]). Mortality rates in
      children aged 1-4 years were 3.06 per 1,000 person-years (95% CI: 2.58-3.63) for
      malaria, and 1.05 per 1,000 person-years (95% CI: 0.79-1.41) for ARI. The HIV
      related mortality rate in this age group was 1.17 per 1,000 person-years (95% CI:
      0.89-1.54). Pulmonary tuberculosis and communicable diseases other than malaria,
      HIV/AIDS and ARI were the main killers of adults aged 15 years and over. Stroke
      related mortality increased to become the leading cause of death among the
      elderly aged 60 years or more in 2005-2007. CONCLUSIONS: Mortality in the
      Farafenni HDSS area was dominated by communicable diseases. Malaria and ARI were
      the leading causes of death in the general population. In addition to these,
      diarrhoeal disease was a particularly important cause of death among children
      under 5 years of age, as was pulmonary tuberculosis among adults aged 15 years
      and above.

PMID- 25377345
TI  - EMIRA: Ecologic Malaria Reduction for Africa--innovative tools for integrated
      malaria control.
AB  - BACKGROUND: Malaria control is based on early treatment of cases and on vector
      control. The current measures for malaria vector control in Africa are mainly
      based on long-lasting insecticide treated nets (LLINs) and to a much smaller
      extent on indoor residual spraying (IRS). A third pillar in the fight against the
      malaria vector, larval source management (LSM), has virtually not been used in
      Africa since the ban of DDT in the 1960s. Within the light of recent WHO
      recommendations for Bacillus thuringiensis israelensis (Bti) use against malaria
      and other vector species, larval source management could see a revival in the
      upcoming years. In this project we analyze the ecologic and health impacts as
      well as the cost effectiveness of larval source management under different
      larviciding scenarios in a health district in Burkina Faso. METHODS: The project
      is designed as prospective intervention study with duration of three years (2013
      2015). Its spatial scale includes three arms of interventions and control,
      comprising a total of 127 villages and the district capital Nouna in the extended
      HDSS (Health Demographic Surveillance System) of the Kossi province. Baseline
      data on mosquito abundance, parasitemia in U5 children, and malaria related
      morbidity and mortality are gathered over the project duration. Besides the
      outcome on ecologic and health parameters, the economic costs are seized and
      valued against the achieved health benefits. CONCLUSIONS: Risk map based, guided
      larvicide application might be a possibility to further decrease economic cost of
      LSM and facilitate its faster incorporation to integrated malaria control
      programs. Given the limited resources in many malaria endemic countries, it is of
      utmost importance to relate the costs of novel strategies for malaria prevention
      to their effect on the burden of the disease. Occurring costs and the impact on
      the health situation will be made comparable to other, existing intervention
      strategies, allowing stakeholders and policymakers decision making.

PMID- 25377346
TI  - Moving towards better cause of death registration in Africa and Asia.

PMID- 25377348
TI  - Building new roles and relationships in research: a model of patient engagement
      research.
AB  - PURPOSE: Patient engagement is influenced by institutional ideologies,
      professional attitudes and patient readiness to accept new, engaged roles. This
      article provides an opportunity to consider a new role for patients who are
      trained to conduct patient experience research using qualitative methods.
      METHODS: The emergence of the role of patient engagement researcher was studied
      using a grounded theory with 21 patients over one-year internship and 125
      research participants. Data were collected using tape recordings, field notes and
      student assignments. These were analyzed using open and selective coding,
      memoing, categorizing themes. RESULTS: Patients' education level (from high
      school to PhD), cultural background (immigrant experience, seniors), employment
      (employed full or part time, receiving disability benefits or retired), age (late
      30 s-75) and gender (17 women and four men) were diverse. Main categories
      (emancipating patient experience; qualifying for research; leading sitting down;
      working data together; seeding change) are organized by the dialectic of co
      creation as the roles of patient and researcher merge. A theoretical model is
      proposed. DISCUSSION: The theoretical model provides a glimpse into the process
      of merging two distinct roles of patient and researcher and in the process
      unleashes a force for change. CONCLUSIONS: The emergence of a dialectic from
      polar opposite roles is difficult to locate in health or other institutions where
      power differentials exist but there are indications that this new role might
      become a template for other merged roles in patient-led medical teams.

PMID- 25377347
TI  - Catalyst-controlled stereoselective olefin metathesis as a principal strategy in
      multistep synthesis design: a concise route to (+)-neopeltolide.
AB  - Molybdenum-, tungsten-, and ruthenium-based complexes that control the
      stereochemical outcome of olefin metathesis reactions have been recently
      introduced. However, the complementary nature of these systems through their
      combined use in multistep complex molecule synthesis has not been illustrated. A
      concise diastereo- and enantioselective route that furnishes the anti
      proliferative natural product neopeltolide is now disclosed. Catalytic
      transformations are employed to address every stereochemical issue. Among the
      featured processes are an enantioselective ring-opening/cross-metathesis promoted
      by a Mo monoaryloxide pyrrolide (MAP) complex and a macrocyclic ring-closing
      metathesis that affords a trisubstituted alkene and is catalyzed by a Mo
      bis(aryloxide) species. Furthermore, Z-selective cross-metathesis reactions,
      facilitated by Mo and Ru complexes, have been employed in the stereoselective
      synthesis of the acyclic dienyl moiety of the target molecule. 

PMID- 25377349
TI  - Engaging Latina cancer survivors, their caregivers, and community partners in a
      randomized controlled trial: Nueva Vida intervention.
AB  - INTRODUCTION: Few studies have evaluated interventions to improve quality of life
      (QOL) for Latina breast cancer survivors and caregivers. Following best practices
      in community-based participatory research (CBPR), we established a multi-level
      partnership among Latina survivors, caregivers, community-based organizations
      (CBOs), clinicians, and researchers to evaluate a survivor-caregiver QOL
      intervention. METHODS: A CBO in the mid-Atlantic region, Nueva Vida, developed a
      patient-caregiver program called Cuidando a mis Cuidadores (Caring for My
      Caregivers), to improve outcomes important to Latina cancer survivors and their
      families. Together with an academic partner, Nueva Vida and three CBOs
      established a multi-level team of researchers, clinicians, Latina cancer
      survivors, and caregivers to conduct a national randomized trial to compare the
      patient-caregiver program to usual care. RESULTS: Incorporating team feedback and
      programmatic considerations, we adapted the prior patient-caregiver program into
      an 8-session patient- and caregiver-centered intervention that includes skill
      building workshops such as managing stress, communication, self-care, social well
      being, and impact of cancer on sexual intimacy. We will measure QOL domains with
      the patient-reported outcomes measurement information system, dyadic
      communication between the survivor and caregiver, and survivors' adherence to
      recommended cancer care. To integrate the intervention within each CBO, we
      conducted interactive training on the protection of human subjects, qualitative
      interviewing, and intervention delivery. CONCLUSION: The development and
      engagement process for our QOL intervention study is innovative because it is
      both informed by and directly impacts underserved Latina survivors and
      caregivers. The CBPR-based process demonstrates successful multi-level patient
      engagement through collaboration among researchers, clinicians, community
      partners, survivors, and caregivers.

PMID- 25377350
TI  - A confirmatory factor analysis of the Resilience Scale adapted to chronic pain
      (RS-18): new empirical evidence of the protective role of resilience on pain
      adjustment.
AB  - PURPOSE: Recent attention has focused on resilience as an important process in
      the experience and management of chronic pain. In this context, resilience is
      considered as a psychological factor that promotes adaptive responses to pain and
      pain-related life adversities. Current research suggests that it is a relevant
      variable in the prediction of pain adjustment among chronic pain patients.
      Recently, it was adapted the Resilience Scale to patients suffering chronic
      musculoskeletal pain (RS-18). The aims of this study were to confirm the internal
      structure of the RS-18 and to present new empirical evidence regarding its
      validity. METHODS: A sample of 592 patients with chronic musculoskeletal back
      pain completed a battery of instruments to assess resilience, anxiety
      sensitivity, catastrophizing, fear-avoidance beliefs, hypervigilance, pain
      acceptance, and pain adjustment variables (pain intensity, emotional distress,
      functional impairment, and daily functioning). RESULTS: Confirmatory factor
      analysis supported the validity of the RS-18 and a single-factor solution. A
      series of moderated multiple regression analysis showed that resilience is a
      relevant psychological variable that not only independently predicts better pain
      adjustment, but also moderates the relationships between several psychological
      pain-related variables and pain adjustment variables. CONCLUSIONS: These findings
      give empirical support to the consideration of resilience as a protective
      variable in chronic pain adjustment and highlight the consideration that
      improving resilient behaviour could be an important target for the treatment of
      pain patients.

PMID- 25377351
TI  - The role of Sequence Type (ST) 131 in adult community-onset non-ESBL-producing
      Escherichia coli bacteraemia.
AB  - BACKGROUND: To compare the epidemiological and clinical features and outcome in
      clonal group O25b/ST131 and non-clonal group O25b/ST131 in adult patients with
      non-extended-spectrum B-lactamase (ESBL)-producing Escherichia coli (E. coli)
      bacteraemia. METHODS: We collected 371 consecutive isolates with community-onset
      non-ESBL producing E. coli bloodstream infection in 2010 in a 1200-bed hospital
      in Taiwan. Twenty adult patients with clonal group O25b/ST131 and 40 patients
      with non-clonal group O25b/ST131 were compared. RESULT: Clonal group O25b/ST131
      accounted for 5.9% of total isolates. The underlying disease and healthcare
      associated risk factors were similar in the case and control groups. Patients
      with the clonal group O25b/ST131 were less likely to have intra-abdominal
      infection (0% vs. 22.5%; p < 0.05) than patients from the control group. The Day
      30 mortality rate was similar in the case and control groups (15% vs. 12.5%).
      CONCLUSIONS: Clonal group O25b/ST131 was found in both multidrug-resistant and
      susceptible E. coli strains, causing community-onset bloodstream infection.
      Although O25b/ST131 does not lead to a higher mortality than other isolates,
      choosing an appropriate antimicrobials in the empirical therapy of community
      onset E. coli bacteraemia has become more challenging.

PMID- 25377352
TI  - Vasopressin aggravates cardiopulmonary bypass-induced gastric mucosal ischemia.
AB  - BACKGROUND/AIM: Upper gastrointestinal bleeding (UGIB) is one of the most
      frequent gastrointestinal complications after cardiac surgery with
      cardiopulmonary bypass (CPB). Endothelin expression and microcirculatory
      dysfunction have been shown to be involved in UGIB. The aim of this study was to
      analyze the effect of vasopressin during CPB on the gastric mucosal
      microcirculation and the involvement of the endothelin system. METHODS: Eighteen
      pigs were randomized into three groups (n = 6 each): group I = sham, group II =
      CPB (1-hour CPB) and group III = CPB + vasopressin (1-hour CPB and vasopressin
      administration during CPB to maintain baseline arterial pressure). All animals
      were observed for a further 90 min after termination of CPB. Systemic
      hemodynamics as well as blood flow and oxygen saturation of the gastric mucosa
      were measured continuously. At the end of the experiment, the gastric mucosal
      expressions of endothelin-1 (ET-1) and its receptor subtypes A (ET(A)) and B
      (ET(B)) were determined by polymerase chain reaction. Gastric mucosal injury,
      apoptotic cell death and leukocytic infiltration were determined by histology and
      immunohistochemical analyses of cleaved caspase-3 and myeloperoxidase. RESULTS:
      CPB decreased gastric microvascular perfusion, which was associated with an
      increased expression of ET-1 and ET(A). Vasopressin aggravated the CPB-associated
      malperfusion, whereas it completely abrogated the upregulation of ET-1 and ET(A).
      Interestingly, vasopressin did not induce gastric mucosal morphologic injury,
      leukocytic infiltration or apoptotic cell death. CONCLUSION: Vasopressin
      aggravates CPB-associated microvascular malperfusion of the gastric mucosa but
      does not induce gastric mucosal injury.

PMID- 25377353
TI  - Improving legume nodulation and Cu rhizostabilization using a genetically
      modified rhizobia.
AB  - The rhizobia-legume interaction has been proposed as an interesting and
      appropriate tool for rhizostabilization of soils contaminated with heavy metals.
      One of the main requirements to use this symbiosis is the availability of
      tolerant and symbiotically effective rhizobia. The aim of this work was to
      improve the symbiotic properties of the arsenic-resistant wild-type strain
      Ensifer medicae MA11 in Cu-contaminated substrates. The copAB genes from a Cu
      resistant Pseudomonas fluorescens strain were expressed in E. medicae MA11 under
      the control of the nifH promoter. The resulting strain E. medicae MA11-copAB was
      able to alleviate the toxic effect of Cu in Medicago truncatula. At 300 uM Cu,
      root and shoot dry matter production, nitrogen content, number of nodules and
      photosynthetic rate were significantly reduced in plants inoculated with the wild
      type strain. However, these parameters were not altered in plants inoculated with
      the genetically modified strain. Moreover, nodules elicited by this strain were
      able to accumulate twofold the Cu measured in nodules formed by the wild-type
      strain. In addition, the engineered E. medicae strain increased Cu accumulation
      in roots and decreased the content in shoots. Thus, E. medicae MA11-copAB
      increased the capacity of M. truncatula to rhizostabilize Cu, decreasing the
      translocation factor and avoiding metal entry into the food chain. The plasmid
      containing the nifH promoter-copAB construct could be a useful biotool for Cu
      rhizostabilization using legumes, since it can be transferred to different
      rhizobia microsymbionts of authoctonous legumes growing in Cu-contaminated soils.

PMID- 25377355
TI  - Community stroke rehabilitation teams: providing home-based stroke rehabilitation
      in Ontario, Canada.
AB  - BACKGROUND: Community stroke rehabilitation teams (CSRTs) provide a community
      based, interdisciplinary approach to stroke rehabilitation. Our objective was to
      assess the effectiveness of these teams with respect to client outcomes. METHODS:
      Functional, psychosocial, and caregiver outcome data. were available at intake,
      discharge from the program, and six-month follow-up. Repeated measures analysis
      of covariance was performed to assess patient changes between time points for
      each outcome measure. RESULTS: A total of 794 clients met the inclusion criteria
      for analysis (54.4% male, mean age 68.5+/-13.0 years). Significant changes were
      found between intake and discharge on the Hospital Anxiety and Depression Scale
      total score (p=0.017), Hospital Anxiety and Depression Scale Anxiety subscale
      (p<0.001), Functional Independence Measure (p<0.001), Reintegration to Normal
      Living Index (p=0.01), Bakas Caregiver Outcomes Scale (p<0.001), and Caregiver
      Assistance and Confidence Scale assistance subscale (p=0.005). Significant gains
      were observed on the strength, communication, activities of daily living, social
      participation, memory, and physical domains of the Stroke Impact Scale (all
      p<0.001). These improvements were maintained at the 6-month follow-up. No
      significant improvements were observed upon discharge on the memory and thinking
      domain of the Stroke Impact Scale; however, there was a significant improvement
      between admission and follow-up (p=0.002). All significant improvements were
      maintained at the 6-month follow-up. CONCLUSIONS: Results indicate that the
      community stroke rehabilitation teams were effective at improving the functional
      and psychosocial recovery of patients after stroke. Importantly, these gains were
      maintained at 6 months postdischarge from the program. A home-based, stroke
      specific multidisciplinary rehabilitation program should be considered when
      accessibility to outpatient services is limited.

PMID- 25377354
TI  - Conserved sequence-specific lincRNA-steroid receptor interactions drive
      transcriptional repression and direct cell fate.
AB  - The majority of the eukaryotic genome is transcribed, generating a significant
      number of long intergenic noncoding RNAs (lincRNAs). Although lincRNAs represent
      the most poorly understood product of transcription, recent work has shown
      lincRNAs fulfill important cellular functions. In addition to low sequence
      conservation, poor understanding of structural mechanisms driving lincRNA biology
      hinders systematic prediction of their function. Here we report the molecular
      requirements for the recognition of steroid receptors (SRs) by the lincRNA growth
      arrest-specific 5 (Gas5), which regulates steroid-mediated transcriptional
      regulation, growth arrest and apoptosis. We identify the functional Gas5-SR
      interface and generate point mutations that ablate the SR-Gas5 lincRNA
      interaction, altering Gas5-driven apoptosis in cancer cell lines. Further, we
      find that the Gas5 SR-recognition sequence is conserved among haplorhines, with
      its evolutionary origin as a splice acceptor site. This study demonstrates that
      lincRNAs can recognize protein targets in a conserved, sequence-specific manner
      in order to affect critical cell functions. 

PMID- 25377356
TI  - Sleepiness and performance is disproportionate in patients with non-organic
      hypersomnia in comparison to patients with narcolepsy and mild to moderate
      obstructive sleep apnoea.
AB  - BACKGROUND/AIMS: Clinical differentiation between organic hypersomnia and non
      organic hypersomnia (NOH) is challenging. We aimed to determine the diagnostic
      value of sleepiness and performance tests in patients with excessive daytime
      sleepiness (EDS) of organic and non-organic origin. METHODS: We conducted a
      retrospective comparison of the multiple sleep latency test (MSLT),
      pupillography, and the Steer Clear performance test in three patient groups
      complaining of EDS: 19 patients with NOH, 23 patients with narcolepsy (NAR), and
      46 patients with mild to moderate obstructive sleep apnoea syndrome (OSAS).
      RESULTS: As required by the inclusion criteria, all patients had Epworth
      Sleepiness Scale (ESS) scores >10. The mean sleep latency in the MSLT indicated
      mild objective sleepiness in NOH (8.1 +/- 4.0 min) and OSAS (7.2 +/- 4.1 min),
      but more severe sleepiness in NAR (2.5 +/- 2.0 min). The difference between NAR
      and the other two groups was significant; the difference between NOH and OSAS was
      not. In the Steer Clear performance test, NOH patients performed worst (error
      rate = 10.4%) followed by NAR (8.0%) and OSAS patients (5.9%; p = 0.008). The
      difference between OSAS and the other two groups was significant, but not between
      NOH and NAR. The pupillary unrest index was found to be highest in NAR (11.5)
      followed by NOH (9.2) and OSAS (7.4; n.s.). CONCLUSION: A high error rate in the
      Steer Clear performance test along with mild sleepiness in an objective
      sleepiness test (MSLT) in a patient with subjective sleepiness (ESS) is
      suggestive of NOH. This disproportionately high error rate in NOH may be caused
      by factors unrelated to sleep pressure, such as anergia, reduced attention and
      motivation affecting performance, but not conventional sleepiness measurements.

PMID- 25377357
TI  - Surgical management of a traumatic dislocation of the sternum in an English
      bulldog.
AB  - A nine-year-old English bulldog presented with an acute history of dyspnoea,
      tachycardia and discomfort localising to the ventral thorax following a fall down
      the stairs that morning. After the dog was stabilised, thoracic radiographs
      revealed a luxation of the third and fourth sternebrae with dorsal displacement
      of the caudal segment. The sternum was reduced and stabilised with a contoured 12
      hole 3 . 5-mm dynamic compression plate applied to the ventral surface of the
      sternum. The dog's initial recovery was rapid, cardiorespiratory parameters
      returning to normal in the first 24 hours. For 2 weeks postoperatively the dog
      exhibited difficulty in rising from a prone position. After this time there was a
      full recovery. Clinical examination at 8 months postoperatively did not reveal
      any abnormalities. Telephone follow-up was performed at 18 months and no
      complications or cardiorespiratory compromise were reported. To the authors'
      knowledge, this is the first reported case of a traumatic dislocation of the
      sternum and its management in the dog. 

PMID- 25377359
TI  - Minimal residual disease as biomarker for optimal biologic dosing of ARA-C in
      patients with acute myeloid leukemia.
AB  - We assessed by flow cytometry minimal residual disease (MRD) in patients with
      acute myeloid leukemia (AML) given standard-dose (SDAC) and high-dose ARA-C
      (HDAC) regimens. Of 163 patients enrolled, 130 (median age, 45 years; range, 18
      59 years) qualified for analysis, all achieving complete remission after
      treatment with SDAC (n = 78) or HDAC (n = 52) plus etoposide and daunorubicin.
      Consolidation consisted of intermediate-dose ARA-C and daunorubicin. MRD
      negativity was significantly more frequent in the SDAC vs. HDAC arm after both
      induction (37% vs. 15%, P = 0.007) and consolidation (44% vs. 18%, P = 0.002).
      Respective median residual leukemic cell counts with SDAC and HDAC use were 1.5 *
      10(-3) and 4 * 10(-3) (P = 0.033) after induction and 5.7 * 10(-4) and 2.9 * 10(
      3) (P = 0.008) after consolidation. Based on ARA-C schedule and post
      consolidation MRD status, the four patient groups (SDAC-MRD(-) , HDAC-MRD(-) ,
      SDAC-MRD(+) , and HDAC-MRD(+) ) displayed 5-year overall survival rates of 60%,
      33%, 24%, and 42% (P = 0.007), respectively, with 24%, 35%, 74%, and 48% (P <
      0.0001) respective cumulative incidence of relapse estimates. MRD may serve as a
      biomarker for optimal biologic dosing of ARA-C, and SDAC regimen appears to yield
      more frequent MRD negativity.

PMID- 25377361
TI  - A multicenter randomized double-blind study: comparison of the Epley, Semont, and
      sham maneuvers for the treatment of posterior canal benign paroxysmal positional
      vertigo.
AB  - We evaluated the short-term efficacy of Epley, Semont, and sham maneuvers for
      resolving posterior canal benign paroxysmal positional vertigo (BPPV) in a
      prospective multicenter randomized double-blind controlled study. Subjects were
      randomly divided into three groups: Epley (36 patients), Semont (32 patients),
      and sham (Epley maneuver for the unaffected side, 31 patients). Out of 14
      institutes which participated in this study, 5 institutes had previous experience
      of the Epley but not the Semont maneuver and the other 9 had previous experience
      of both maneuvers. Each maneuver was repeated twice if there was still positional
      vertigo or nystagmus on day 0, and the presence of nystagmus and vertigo on
      positional testing were evaluated immediately, 1 day, and 1 week after treatment.
      After the first maneuver, the Epley group showed a significantly higher
      resolution rate of positional nystagmus than the Semont or sham groups (63.9,
      37.5, and 38.7%, respectively). After the second maneuver, the resolution rate
      (83.3%) of the Epley group was significantly higher than that (51.6%) of the sham
      group. At 1 day and 1 week after treatment, the resolution rate of the Epley
      group was significantly higher than those of the other groups. Similar results
      were seen for the resolution of positional vertigo. The Epley maneuver showed
      persistent resolution rates of positional vertigo and nystagmus without a fatigue
      phenomenon. The Epley maneuver was significantly more effective per maneuver than
      Semont or sham maneuvers for the short-term treatment of posterior canal BPPV.
      The Semont maneuver showed a higher success rate than the sham maneuver, but it
      was not significantly different.

PMID- 25377360
TI  - Novel isotopic N,N-dimethyl leucine (iDiLeu) reagents enable absolute
      quantification of peptides and proteins using a standard curve approach.
AB  - Absolute quantification of protein targets using liquid chromatography-mass
      spectrometry (LC-MS) is a key component of candidate biomarker validation. One
      popular method combines multiple reaction monitoring (MRM) using a triple
      quadrupole instrument with stable isotope-labeled standards (SIS) for absolute
      quantification (AQUA). LC-MRM AQUA assays are sensitive and specific, but they
      are also expensive because of the cost of synthesizing stable isotope peptide
      standards. While the chemical modification approach using mass differential tags
      for relative and absolute quantification (mTRAQ) represents a more economical
      approach when quantifying large numbers of peptides, these reagents are costly
      and still suffer from lower throughput because only two concentration values per
      peptide can be obtained in a single LC-MS run. Here, we have developed and
      applied a set of five novel mass difference reagents, isotopic N,N-dimethyl
      leucine (iDiLeu). These labels contain an amine reactive group, triazine ester,
      are cost effective because of their synthetic simplicity, and have increased
      throughput compared with previous LC-MS quantification methods by allowing
      construction of a four-point standard curve in one run. iDiLeu-labeled peptides
      show remarkably similar retention time shifts, slightly lower energy thresholds
      for higher-energy collisional dissociation (HCD) fragmentation, and high
      quantification accuracy for trypsin-digested protein samples (median errors
      <15%). By spiking in an iDiLeu-labeled neuropeptide, allatostatin, into mouse
      urine matrix, two quantification methods are validated. The first uses one
      labeled peptide as an internal standard to normalize labeled peptide peak areas
      across runs (<19% error), whereas the second enables standard curve creation and
      analyte quantification in one run (<8% error). 

PMID- 25377363
TI  - Long-acting injectable (depot) antipsychotics and changing treatment philosophy:
      possible contribution to integrative care and personal recovery of schizophrenia.

PMID- 25377362
TI  - "It is all about the fear of being discriminated [against]...the person suffering
      from HIV will not be accepted": a qualitative study exploring the reasons for
      loss to follow-up among HIV-positive youth in Kisumu, Kenya.
AB  - BACKGROUND: Youth represent 40% of all new HIV infections in the world, 80% of
      which live in sub-Saharan Africa. Youth living with HIV (YLWH) are more likely to
      become lost to follow-up (LTFU) from care compared to all other age groups. This
      study explored the reasons for LTFU among YLWH in Kenya. METHODS: Data was
      collected from: (1) Focus group Discussions (n = 18) with community health
      workers who work with LTFU youth. (2) Semi-structured interviews (n = 27) with
      HIV + youth (15-21 years old) that had not received HIV care for at least four
      months. (3) Semi-structured interviews (n = 10) with educators selected from
      schools attended by LTFU interview participants. Transcripts were coded and
      analyzed employing grounded theory. RESULTS: HIV-related stigma was the
      overarching factor that led to LTFU among HIV + youth. Stigma operated on
      multiple levels to influence LTFU, including in the home/family, at school, and
      at the clinic. In all three settings, participants' fear of stigma due to
      disclosure of their HIV status contributed to LTFU. Likewise, in the three
      settings, the dependent relationships between youth and the key adult figures in
      their lives were also adversely impacted by stigma and resultant lack of
      disclosure. Thus, at all three settings stigma influenced fear of disclosure,
      which in turn impacted negatively on dependent relationships with adults on whom
      they rely (i.e. parents, teachers and clinicians) leading to LTFU. CONCLUSIONS:
      Interventions focusing on reduction of stigma, increasing safe disclosure of HIV
      status, and improved dependent relationships may improve retention in care of
      YLWH.

PMID- 25377364
TI  - Is non-pharmacological treatment an option for certain schizophrenia patients?
AB  - BACKGROUND: Schizophrenia treatment has been debated at length and presently
      pharmacological treatment is being advocated as the most beneficial for patients.
      However, research has shown contradictory results regarding the suitability of
      pharmacological treatment for certain groups of schizophrenia patients. METHODS:
      The present review discusses results from the literature indicating good outcomes
      only for patients who adhered to prescribed pharmacological treatments. It also
      describes studies favoring non-drug treatments in certain schizophrenic patients.
      RESULTS: The authors described two groups of patients where the long-term use of
      neuroleptics may be useless, if not harmful. The first group comprised
      schizophrenic people with a single psychotic episode and therefore very good
      prognosis. In their case, the prolonged use of antipsychotics would not be
      beneficial due to pharmacological and social (stigma) side effects. Further
      research is warranted to identify and investigate biological, environmental, and
      psychological factors associated with single-episode schizophrenia. The second
      group comprised ultra-resistant schizophrenic patients. In their case, in the
      absence of a therapeutic response in acute episodes or aggressive behavior,
      clinicians should use short episodes of treatment with benzodiazepines or other
      sedative medications such as mood stabilizers. CONCLUSIONS: The present paper
      attempted to answer the important question as to whether all schizophrenic people
      should be treated with antipsychotics for the same good prognosis. The authors
      have provided solutions for better outcomes in a greater number of patients using
      alternative treatment after identifying schizophrenic patients who should not
      receive neuroleptic treatment. Suggestions for future research are also
      discussed.

PMID- 25377365
TI  - Prolidase activity and oxidative stress in patients with major depressive
      disorder.
AB  - BACKGROUND: The aim of the current study was to determine whether the serum
      prolidase levels are associated with the etiopathogenesis of depression. SUBJECTS
      AND METHODS: This study included 29 patients with major depressive disorder
      (MDD), who were consecutively recruited from the psychiatric outpatient clinic,
      and 30 healthy individuals recruited from the general community. Each patient
      underwent a detailed diagnostic evaluation by two psychiatrists using the
      Structured Clinical Interview for DSM-IV (SCID-I). Serum prolidase activity and
      oxidative parameters were measured in the patient and control groups. The
      severity of depressive symptoms was assessed using the Hamilton Depression Rating
      Scale. RESULTS: Serum prolidase level was significantly higher in patients with
      MDD compared to healthy subjects (p<0.001). Total Oxidant Status (TOS) levels and
      Oxidative Stress Index (OSI) were also significantly higher in patients with MDD
      (p<0.001), whereas no significant difference was observed between the groups in
      the TAS levels (p=0.297). Serum prolidase level did not show any correlation with
      markers of oxidative stress in patients with MDD. CONCLUSION: Increased serum
      prolidase levels in patients with MDD may be interpreted as the interaction of
      prolidase activity, glutamate transmission and oxidative stress. It is suggested
      that prolidase activity is involved in the etiopathogenesis of depressive
      disorder.

PMID- 25377366
TI  - Do 'school coaches' make a difference in school-based mental health promotion?
      Results from a large focus group study.
AB  - BACKGROUND: Mental disorders in children and adolescents are common and have
      serious consequences. Schools present a key opportunity to promote mental health
      and implement prevention measures. Four school coaches in five German schools
      were enlisted to engage students, teachers and parents in building a sustainably
      healthy school and classroom climate. SUBJECTS AND METHODS: Altogether, 58 focus
      groups with students (N=244), parents (N=54) and teachers (N=62) were conducted
      longitudinally. Topics included: (1) the development of the school and classroom
      climate, (2) the role of mental health in the regular curriculum, and (3) the
      role of school coaches in influencing these aspects. RESULTS: Over time, school
      coaches became trusted reference persons for an increasing number of school
      system members. They were able to positively influence the school and classroom
      climate by increasing the awareness of students, teachers and parents of mental
      health in daily routines. Nevertheless, topics like bullying and student
      inclusion remained an issue at follow-up. CONCLUSIONS: Overall, the school coach
      intervention is a good model for establishing the topic of mental health in
      everyday school life and increasing its importance. Future efforts will focus on
      building self-supporting structures and networks in order to make these efforts
      sustainable.

PMID- 25377367
TI  - High risk of Internet addiction and its relationship with lifetime substance use,
      psychological and behavioral problems among 10(th) grade adolescents.
AB  - BACKGROUND: The aim of this study was to investigate the relationship of higher
      risk of Internet addiction (HRIA) with lifetime substance use, psychological and
      behavioral factors among Turkish 10(th) grade students. SUBJECTS AND METHODS:
      Cross-sectional online self-report survey conducted in 45 schools from the 15
      districts in Istanbul, Turkey. A representative sample of 4957 10(th) grade
      students was studied between October 2012 and December 2012. Other than
      sociodemographic variables the survey included the Addiction Profile Index
      Internet Addiction Form-Screening Version (BAPINT-SV) and the Psychological
      Screening Test for Adolescents (PSTA). RESULTS: The participants were classified
      into two groups as those with HRIA (15.96%) and those with lower risk of Internet
      addiction. The rate of HRIA was higher in the males. The findings indicated that
      HRIA is related with negative consequences in school, lifetime use of tobacco,
      alcohol and/or drug, suicidal thoughts, self-harming and delinquent behaviors.
      CONCLUSIONS: Male gender, lifetime use of tobacco, alcohol and/or drug,
      depression, attention deficit and hyperactivity symptoms and lack of
      assertiveness predicted the HRIA in Turkish 10(th) grade students. Being aware of
      those with HRIA is important in prevention and management of Internet addiction
      as well as other important problems among students, such as substance use.

PMID- 25377368
TI  - Posttraumatic stress disorder in women with war missing family members.
AB  - BACKGROUND: Research in crisis areas indicate that survivors' responses to the
      forced disappearance of family members are similar to reactions to other
      traumatic events. The aim of this study was to determine the presence of symptoms
      of posttraumatic stress disorder (PTSD) in women with war missing family members
      in Bosnia and Herzegovina 18 years after the war in this region (1992-1995).
      SUBJECTS AND METHODS: The study included 160 women aged 47.1+/-14.0 from three
      regions of Bosnia and Herzegovina. It was carried out in the period from April
      2010 to May 2011. Of the 160 participants, 120 women had a war missing family
      member and 40 women had no war missing family members. The Harvard Trauma
      Questionnaire (HTQ), the Beck Depression Inventory (BDI) and the Hamilton Anxiety
      Rating Scale (HAMA) were used for data collection. Basic socio-demographic data
      and data concerning the missing family members were also collected. RESULTS:
      Women with war missing family members experienced significantly more traumatic
      war experiences (18.43+/-5.27 vs 6.57+/-4.34, p<0.001). There was a significant
      difference between the two groups in the total PTSD score (2.48+/-0.59 vs 1.79+/
      0.53, p<0.001), as well as in the intensity of depression (26.63+/-13.05 vs
      10.32+/-6.58, p<0.001) and anxiety (21.0+/-10.69 vs 11.27+/-7.93, p<0.001).
      Anxiety and traumatic war experiences were significant predictors of PTSD in the
      group with war missing family members. CONCLUSIONS: Women with war missing family
      members showed significantly more severe PTSD symptoms. Based on the results of
      this study, it was determined that the forced disappearance of a family member is
      an ambiguous situation that can be characterized as a traumatic experience.

PMID- 25377369
TI  - Post-traumatic stress disorder in parents of children hospitalized in the
      neonatal intensive care unit (NICU): medical and demographic risk factors.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) among parents of neonates
      hospitalized in the Neonatal Intensive Care Units (NICU) stays an underestimated
      problem. We determined the incidence of PTSD in parents and pointed out medical
      and demographic risk factors for PTSD in neonates hospitalized in the NICU.
      SUBJECT AND METHODS: The study involved 39 mothers and 27 fathers of 42 infants
      aged 1 to 16 months who were hospitalized in the NICU of a Children's University
      Hospital during the neonatal period. As a measure of PTSD we used the Polish
      version of the Impact of Event Scale-Revised (IES-R). The current level of stress
      was measured using the Perceived Stress Scale (PSS-10). The author's
      questionnaire contained demographic and medical information on the infants
      hospitalized in the NICU and their parents. Data were statistically analyzed.
      RESULTS: The incidence of PTSD and levels of stress did not differ in the group
      of mothers and fathers. There was a statistically significant difference in the
      severity of PTSD symptoms in general (p=0.006) and the severity of symptoms of
      intrusion (p=0.009) and arousal (p=0.015), which were more pronounced in mothers
      of children hospitalized in the NICU than in their fathers. In the multivariate
      models perceived stress was the only predictor that significantly affected the
      rate of PTSD symptoms in parents. CONCLUSIONS: Since PTSD is a very common
      problem in parents of children hospitalized in the NICU and estimating the risk
      of its occurrence on the basis of collected data is not possible, the parents of
      all those children should be considered at high risk.

PMID- 25377370
TI  - Treatment of insomnia with hypnotics resulting in improved sexual functioning in
      post-menopausal women.
AB  - BACKGROUND: This study sought to determine whether trazodone used in hypnotic
      doses, compared to the hypnotic agent zopiclone, had any specific positive effect
      on sexual function in non-depressive post-menopausal women with insomnia.
      SUBJECTS AND METHODS: Fifty (50) subjects participated in the study. Insomnia and
      sexual performance were evaluated before and after 4 weeks of hypnotic treatment.
      RESULTS: At week four, both treatments improved sleep quality to a similar
      degree. Sexual function also improved significantly with both treatments, with no
      significant difference between the groups. CONCLUSIONS: In post-menopausal women,
      sexual problems and sleep problems may be related and solving sleep problems may
      help sexual functioning, independently of depression.

PMID- 25377371
TI  - Catatonic stupor secondary to gamma-hydroxy-butyric acid (GHB)-dependence and 
      withdrawal syndrome.

PMID- 25377372
TI  - Successful electroconvulsive therapy and improvement of negative symptoms in
      refractory schizophrenia with clozapine-induced seizures: a case report.

PMID- 25377373
TI  - [Prescribed drugs - a new crime field?].
AB  - The first chapter of the following article discusses measures in terms of
      substitution treatment of a program of the Austrian Minister of the Interior. The
      relevance of psychosocial measures and aims of substitution treatment for opioid
      dependent patients is illuminated. The abstinence as the only goal definition is
      modified and by the results of the study PREMOS a target differentiation at
      addiction work is illustrated. The second chapter addresses the misuse of
      prescribed drugs. Thereby police report data will be analyzed and the market
      situation of opioids will be outlined. 

PMID- 25377374
TI  - How addiction develops and what are the consequences - a psychodynamic approach.
      Addiction and psychodynamic aspects.
AB  - BACKGROUND: The reward-system can be differentiated from the motivational system.
      METHODS AND RESULTS: A complex psychodynamic approach (OPD-2) takes into account
      motivational aspects - psychological functioning - the drug and the consequences.
      Multiaxial aspects are necessary. The system is described. CONCLUSIONS: A
      psychodynamic cycle of addiction enables different therapy steps.

PMID- 25377375
TI  - [Internet addiction - between enter and escape].
AB  - Internet addiction, a non-substantial addiction, is to be regarded as a highly
      complex mental disorder which requires complex and diverse treatment options.
      Initially smiled at, it shows, if it were severe, a typical addictive behaviour
      pattern, similar to pathological gambling, oniomanie and workaholism. In the
      International Classification of mental disorders (ICD-10) only pathological
      gambling in the category of impulse control disorders (F63.0) is specified. 

PMID- 25377376
TI  - Addiction between therapy and criminalization.
AB  - The present paper delves into the question of whether and to what extent it is
      appropriate to leave addiction problems between the conflicting priorities of
      therapy and criminalization. After outlining the issue the criminal addictive
      behaviour including crimes associated with drug misuse and with obtaining drugs
      is described. Subsequently it is discussed if and how you could make allowances
      for addiction-related legal insanity in the criminal law sector. Following a few
      remarks on the principle of "voluntary therapy instead of penal sanction" as a
      way to alleviate the strict law on narcotic drugs misuse a summary and an outlook
      with criminal-political demands complete the issue. 

PMID- 25377377
TI  - [Online gaming. Potential risk and prevention programs].
AB  - Online gaming is more and more common and increasingly accessible. Due to a lack
      of social control the participation could be a potential risk for certain
      customers. The given article focuses on prevention measures that are provided by
      the Austrian online gaming operator, the Austrian Lotteries, provider of the
      online gaming platform win2day, in the light of the specifics of Internet gaming
      in order to avoid problems with gaming. 

PMID- 25377378
TI  - [Online-gambling - new hazard potential?].
AB  - Since the new American psychiatric classification, DSM V, was released, bringing
      together substance-related disorders and gambling disorder into one chapter, the
      addictive potential of gambling and sports wagering is beyond all question. Even
      the neurobiological processes of the brain show similarities in all addictive
      disorders. Gambling is more and more shifted into the cyberspace owing to the
      global expansion of the internet. The addictive potential of online-gambling
      seems to be higher than offline, though, which is also reflected by the patient
      population of the outpatient clinic for gambling addiction in Linz. This fact
      poses a challenge for the persons affected, therapists, gambling providers,
      legislator the society as a whole. 

PMID- 25377379
TI  - Frontal corpus callosum alterations in progressive supranuclear palsy but not in
      Parkinson's disease.
AB  - BACKGROUND: Frontal lobe involvement is considered a clinical and magnetic
      resonance imaging (MRI) feature in later stages of progressive supranuclear palsy
      (PSP). OBJECTIVE: Diffusion tensor imaging (DTI) was used to investigate the
      integrity of frontal pathways in PSP and Parkinson's disease (PD) patients.
      METHODS: DTI and 3-D MRI were performed in 15 PSP patients (parkinsonism subtype:
      n = 8; Richardson subtype: n = 7), 15 PD patients, and 18 matched controls. DTI
      analysis was performed in order to identify differences along frontal white
      matter structures including the corpus callosum (CC) and was complemented by
      atlas-based volumetry and planimetry. RESULTS: Significantly reduced regional
      fractional anisotropy was observed for PSP patients versus controls and PSP
      versus PD patients, respectively, in frontal areas including the area II of the
      CC and bilaterally in the callosal radiation. The DTI findings correlated with
      frontal lobe volumes. These differences were not observed between PD patients and
      controls. CONCLUSION: DTI identified a PSP-associated microstructural alteration
      pattern in the frontal lobes and in the CC area II including the corresponding
      bilateral callosal radiation tracts that could not be identified in both control
      samples, supporting the prominent PSP-associated frontal involvement as a
      potential neuroimaging marker.

PMID- 25377380
TI  - Impact of aldosterone on osteoinductive signaling and vascular calcification.
AB  - Vascular calcification is frequently found already in early stages of chronic
      kidney disease (CKD) patients and is associated with high cardiovascular risk.
      The process of vascular calcification is not considered a passive phenomenon but
      involves, at least in part, phenotypical transformation of vascular smooth muscle
      cells (VSMCs). Following exposure to excessive extracellular phosphate
      concentrations, VSMCs undergo a reprogramming into osteo-/chondroblast-like
      cells. Such 'vascular osteoinduction' is characterized by expression of
      osteogenic transcription factors and triggered by increased phosphate
      concentrations. A key role in this process is assigned to cellular phosphate
      transporters, most notably the type III sodium-dependent phosphate transporter
      Pit1. Pit1 expression is stimulated by mineralocorticoid receptor activation.
      Therefore, aldosterone participates in the phenotypical transformation of VSMCs.
      In preclinical models, aldosterone antagonism reduces vascular osteoinduction.
      Patients with CKD suffer from hyperphosphatemia predisposing to vascular
      osteogenic transformation, potentially further fostered by concomitant
      hyperaldosteronism. Clearly, additional research is required to define the role
      of aldosterone in the regulation of osteogenic signaling and the consecutive
      vascular calcification in CKD, but more generally also other diseases associated
      with excessive vascular calcification and even in individuals without overt
      disease.

PMID- 25377381
TI  - Iminosugar-based galactoside mimics as inhibitors of galactocerebrosidase: SAR
      studies and comparison with other lysosomal galactosidases.
AB  - Several families of iminosugar-based galactoside mimics were designed,
      synthesized, and evaluated as galactocerebrosidase (GALC) inhibitors. They were
      also tested as inhibitors of lysosomal beta- and alpha-galactosidases in order to
      find new potent and selective pharmacological chaperones for treatment of the
      lysosomal storage disorder, Krabbe disease. Whereas 1-C-alkyl imino-L-arabinitols
      are totally inactive toward the three enzymes, 1-C-alkyl imino-D-galactitols were
      found to be active only toward alpha-galactosidase A. Finally, 1-N-iminosugars
      provided the best results, as 4-epi-isofagomine was found to be a good inhibitor
      of both lysosomal beta-galactosidase and GALC. Further elaboration of this
      structure is required to achieve selectivity between these two galactosidases.

PMID- 25377382
TI  - A mixed-methods examination of communication between oncologists and primary care
      providers among primary care physicians in underserved communities.
AB  - BACKGROUND: Research has demonstrated that communication and care coordination
      improve cancer patient outcomes. To improve communication and care coordination,
      it is important to understand primary care providers' (PCPs') perceptions of
      communication with oncologists as well as PCPs' communication needs. METHODS: A
      mixed-methods approach was used in the present study. In the qualitative phase of
      the study, 18 PCPs practicing in underserved, minority communities were
      interviewed about their experiences communicating with oncologists. In the
      quantitative phase of the study, 128 PCPs completed an online survey about their
      preferences, experiences, and satisfaction with communication with oncologists.
      RESULTS: Results indicated a PCP-oncologist gap in communication occurred between
      diagnosis and treatment. PCPs wanted more communication with oncologists, updates
      on their patients' prognosis throughout treatment, and to be contacted via
      telephone or email and saw their role as crucial in providing supportive care for
      their patients. CONCLUSIONS: Although PCPs recognize that they play a critical,
      proactive role in supporting patients throughout the continuum of their cancer
      care experience, existing norms regarding postreferral engagement and oncologist
      PCP communication often hinder activation of this role among PCPs. Expected
      standards regarding the method, frequency, and quality of postreferral
      communication should be jointly articulated and made accountable between PCPs and
      oncologists to help improve cancer patients' quality of care, particularly in
      minority communities.

PMID- 25377383
TI  - Accurate segmental motor innervation of human lower-extremity skeletal muscles.
AB  - BACKGROUND: There is limited knowledge about accurate segmental motor innervation
      of the human lower extremity skeletal muscles. The aim of the present study was
      to explore the truth of segmental motor innervation of the lower extremity.
      METHODS: Included in this study were 20 patients with unilateral fracture of the
      sacrum and sacral nerve injury, who underwent internal fixation and decompression
      of the sacral nerve in our hospital between June 2009 and January 2014. L4-S4
      nerve roots of the uninjured side were stimulated during operation. Motor
      innervation was determined by stimulating the spinal nerves with supramaximal
      intensity. RESULTS: We found the gluteus medius and the gluteus maximus were both
      mainly innervated by L5 and S1. In addition, the nerve fibres that innervated the
      extensor digitorum brevis, the abductor hallucis and the flexor digitorum brevis
      were mainly from S2 to S3. CONCLUSIONS: Our study provides the
      electrophysiological mapping of the segmental anatomy of the human lower
      extremity muscles, which should be clinically useful in helping the diagnosis and
      treatment of nerve injury and neuropathies.

PMID- 25377384
TI  - AlloDerm for duraplasty in Chiari malformation: superior outcomes.
AB  - BACKGROUND: Autologous pericranium, fascia lata (either as autograft or
      allograft), bovine pericardium (DuraGuard), fetal bovine tissue (Durepair),
      processed collagen matrix (DuraGen), and synthetic fabrics (e.g., synthetic
      Goretex graft) have all been used for duraplasty in Chiari decompression surgery,
      and no consensus exists as to the optimal material. We reviewed our experience to
      compare the incidence of graft-related complications associated with using
      acellular human dermis allograft (AlloDerm) with those of DuraGuard, DuraGen, and
      Durepair. METHODS: In a retrospective cohort chart review, our cohort included
      119 patients who underwent 128 Chiari decompression procedures by a single
      surgeon from January 1, 1997, through July 31, 2012. Age, sex, smoking status,
      weight, and the type of dural graft used were analyzed with univariate
      statistical tests. Dural grafts were selected based on the commercial products
      available at the time of surgery during this 15-year period. RESULTS: The
      reoperation rate for cerebrospinal fluid leak causing pseudomeningocele was 2.2 %
      (1/46 cases) with the AlloDerm graft and 17.1 % (14/82 cases) with other
      materials (p = 0.01). Each of the non-AlloDerm grafts had a higher reoperation
      rate than AlloDerm when analyzed separately. Not using AlloDerm was the only
      statistically significant factor for the need for reoperation (p = 0.01).
      CONCLUSIONS: The use of the AlloDerm dural graft for duraplasty in Chiari
      decompressions resulted in a significantly lower pseudomeningocele formation than
      the use of any other type of dural graft. There was no association between
      patient age, sex, extra weight, or smoking status and the need for reoperation.

PMID- 25377385
TI  - True aqueductal tumors: a unique entity.
AB  - BACKGROUND: Pure aqueductal tumors (ATs) differ from pineal region and
      tectal/tegmental tumors in that they are epicentered within the aqueduct.
      Nevertheless, these tumors are rarely described as a separate type of tumor, and
      are often grouped with other lesions located in the same vicinity. The present
      multicenter study focuses on our experience treating patients with pure ATs.
      METHODS: Data from three large tertiary centers was collected retrospectively,
      including presenting symptoms, treatment paradigm, surgical approaches,
      pathology, and outcome. RESULTS: Between 1999 and 2013, 16 patients with AT were
      diagnosed and treated at the three tertiary centers. Ages at presentation ranged
      from 5.5 to 57 years. Thirteen patients presented with hydrocephalus-related
      symptoms, and two were identified incidentally. Thirteen patients underwent an
      endoscopic third ventriculostomy, and two of these underwent a simultaneous
      endoscopic biopsy (one grade II ependymoma, one non-specified low-grade glioma).
      Two others underwent shunt placement. Three patients underwent resection due to
      tumor progression. Pathologies included glioblastoma multiforme, glioneural
      tumor, and ependymoma grade II. All non-resected tumors remained stable or grew
      only minimally. CONCLUSIONS: ATs are a rare entities that usually present with
      obstructive hydrocephalus. Treatment includes primarily cerebrospinal fluid
      drainage (preferably via an endoscopic third ventriculostomy). Simultaneous
      endoscopic biopsy may be done in selected cases. Tumor resection should be
      reserved for growing tumors; the trans-fourth ventricular or trans-choroidal
      approaches are probably safer than other approaches used to reach the tectal
      region.

PMID- 25377386
TI  - Infection of cardiovascular implantable electronic devices: detection with
      sonication, swab cultures, and blood cultures.
AB  - BACKGROUND: The number of patients with cardiovascular implantable electronic
      devices (CIEDs) is increasing. The purpose of this study was to compare three
      methods (sonication, swab cultures, and blood cultures) to detect bacteria in
      infections of CIEDs. METHODS: Patients with pocket infection of CIEDs and/or CIED
      associated infective endocarditis were prospectively included. Generators and
      leads were sonicated together. Swab cultures of the generator pocket and blood
      cultures were performed. RESULTS: Between January 2009 and September 2012, 18
      patients with a CIED infection were recorded, including two definite and four
      possible CIED-IEs. In 17 patients, blood cultures were performed and the device
      was analyzed by sonication. A swab culture from the device pocket was performed
      in 16 cases. Ten (59%) patients received antibiotic therapy before the device was
      removed. In 15 of 16 cases (94%), bacteria were detected by sonication, while
      bacteria were detected in only nine (56%) and seven (41%) cases by swab-and blood
      cultures, respectively. In four cases (24%), sonication was the only method that
      detected bacteria. The following bacteria were detected by sonication:
      methicillin-sensitive Staphylococcus aureus (MSSA; n = 6), coagulase-negative
      staphylococci (CNS; n = 3), Propionibacterium acnes (n = 2), Staphylococcus
      lugdunensis (n = 1), MSSA/Pseudomonas aeruginosa (n = 1),Bacillus cereus (n = 1),
      MSSA/P. acnes (n = 1), andP. acnes/CNS (n = 1). All positive swab cultures and
      all positive blood cultures but one grew the same bacteria as sonication fluid
      cultures. CONCLUSION: Sonication can be more sensitive than swab cultures or
      blood cultures in detecting bacteria in infections of CIEDs.

PMID- 25377387
TI  - Salvage of failed total ankle replacement using tantalum trabecular metal: case
      series.
AB  - BACKGROUND: Although newer generations of total ankle arthroplasty designs have
      better clinical outcomes, failure due to aseptic loosening remains a frequent
      major complication. Arthrodesis is the most common salvage procedure for a failed
      total ankle replacement. There are several arthrodesis techniques each with its
      advantages and disadvantages. We present a technique of ankle arthrodesis for
      failed total ankle replacements using tantalum Trabecular MetalTM (Zimmer,
      Warsaw, IN) with internal fixation, thus sparing the subtalar joint. METHODS:
      Three patients who had undergone arthrodesis for a failed total ankle replacement
      using tantalum Trabecular Metal were retrospectively reviewed. The mean follow-up
      period was 57 (range, 31-86) months. The mean age at ankle arthroplasty was 57
      (range, 33-72) years and at ankle arthrodesis was 63 (range, 44-74) years. The
      mean time from arthroplasty to arthrodesis was 7 (range, 2-11) years. RESULTS:
      The American Orthopaedic Foot and Ankle Society (AOFAS) score improved from 30.7
      (range, 20-39) preoperatively to 72.7 (range, 65-77) postoperatively at the time
      of last follow-up. Arthrodesis was achieved at a mean of 3 months, and there were
      no complications. CONCLUSION: The technique described has several advantages when
      compared to other methods of salvage ankle arthrodesis. The subtalar joint is not
      included in the fusion unless it is degenerative and symptomatic. Height of the
      ankle is maintained throughout the fusion process. Furthermore, Trabecular Metal
      is abundantly available; it avoids donor site morbidity and eliminates the risk
      of transmissible diseases.

PMID- 25377388
TI  - Radiological prevalence of degenerative arthritis of the first
      metatarsophalangeal joint.
AB  - BACKGROUND: The prevalence of osteoarthritis of the first metatarsophalangeal
      joint (MTPJ) has not been completely determined in a population-based study. The
      aim of the study was to determine the age- and gender-related prevalence of
      radiological first MTPJ arthritis. METHODS: We analyzed 517 consecutive
      radiographs of adult patients who presented with acute foot injuries to the
      accident and emergency department over a 6-month period. Radiographs were
      assessed independently by 2 authors using the Hattrup and Johnson grading system
      for osteoarthritic changes in the first MTPJ. RESULTS: The radiographic
      prevalence of MTPJ arthritis in our population was 25% (127/517). Overall
      incidence was higher in females, with 32% (85/269) of females affected in
      comparison to 18% (44/248) of males. Variance between the sexes was insignificant
      until the age of 60, at which point the prevalence rose to 66% (53/80) in females
      compared with 47% (18/38) in males of the same age. CONCLUSIONS: The development
      of first MTPJ arthritis follows a typical pattern of degenerative arthritis, as
      shown in other joints, with increasing age being an important factor. The results
      of this study suggest that first MTPJ arthritis begins to appear in most cases in
      middle age and is significantly more apparent in females. LEVEL OF EVIDENCE:
      Level III, comparative case series.

PMID- 25377390
TI  - Salvage of avascular necrosis of the talus by combined ankle and hindfoot
      arthrodesis without structural bone graft.
AB  - BACKGROUND: Osteonecrosis of the talus is a well-recognized pathology, which can
      result in significant hindfoot collapse resulting in poor function and pain.
      Treatment with intramedullary tibiotalocalcaneal arthrodesis (IMTCA) using a
      retrograde intramedullary nail is widely utilized for severe concomitant
      tibiotalar and subtalar pathologies. This study reports the results of ankle and
      hindfoot arthrodesis in patients with arthritis and deformity caused specifically
      by talar osteonecrosis. METHODS: Fourteen ankle and hindfoot arthrodeses with
      retrograde intramedullary nail were studied, with a mean follow-up of 26 months.
      Medical records were reviewed for operative technique, concomitant procedures,
      bone graft used, and postoperative complications including nonunion, infection,
      nerve injury, wound healing issues, and the need for additional surgeries.
      Clinical outcomes included Visual Analogue Scale for pain, the AOFAS
      Ankle/Hindfoot Score, and the SF-36 questionnaire. RESULTS: Over 80% of cases had
      osteonecrosis involving the entire body of the talus. In 4 cases tibiocalcaneal
      arthrodesis was performed, with the remaining talar head-neck portion fused to
      anterior aspect of tibia. Union was achieved in all cases. The mean preoperative
      VAS score was 6.9 (range 5 to 9, SD +/- 1.5) decreasing to 1.7 (range 0 to 6, SD
      +/- 2.2) postoperatively (P = .00008). The mean preoperative AOFAS score was 32.7
      (range 20 to 46, SD +/- 8.7), increasing to 72.1 (range 46 to 86, SD +/- 10.1, P
      = .00003). The mean preoperative SF-36 physical component score was 30.5 (range
      21 to 42, SD +/- 6.9) increasing to 42.8 (range 20 to 60, SD +/- 11.4)
      postoperatively (P = .02). Complications included 1 stress fracture, 4 hardware
      removals, and 1 superficial infection. CONCLUSION: Ankle and hindfoot arthrosis
      due to extensive talar AVN can be successfully treated with IMTCA.

PMID- 25377389
TI  - Inferior results of salvage arthrodesis after failed ankle replacement compared
      to primary arthrodesis.
AB  - BACKGROUND: Up to now, there has been no evidence that salvage arthrodesis would
      perform inferior when compared with primary ankle arthrodesis. The purpose of
      this study was to compare their clinical and radiographic results. METHODS: A
      retrospective analysis was performed using 2 validated scores and assessment of
      radiographic union by comparing 23 patients who underwent salvage ankle
      arthrodesis (group SA = salvage arthrodesis) after failed total ankle replacement
      with 23 matched patients who received primary ankle arthrodesis (group PA =
      primary arthrodesis). The mean follow-up period was 38 (range 16-92) months in
      group SA and 56 (23-94) months in group PA. RESULTS: Complete union was achieved
      in 17 patients (74%) after a mean time of 50 (13- 114) weeks in group SA and in
      16 patients (70%) after a mean time of 23 (10-115) weeks in group PA. The SF-36
      score averaged 48 points (7-80) in SA and 66 points (14-94; P = .006) in group
      PA. In group SA the mean FFI was 57% (22-82) for pain and 71% (44-98) for
      function. In group PA significantly better results for pain with 34% (0-88; P =
      .002) and function with 48% (1-92; P = .002) were found. CONCLUSION: Salvage
      arthrodesis led to impaired life quality and reduced function combined with
      significantly higher pain when compared with primary ankle arthrodesis. These
      findings can be used to counsel our patients preoperatively. LEVEL OF EVIDENCE:
      Level III, retrospective case series.

PMID- 25377391
TI  - Management of congenital fourth brachymetatarsia by additive autologous
      lengthening osteotomy (AALO): a case series.

PMID- 25377393
TI  - Festive foods.

PMID- 25377392
TI  - Pharmacokinetics and excretion of (14)C-lenvatinib in patients with advanced
      solid tumors or lymphomas.
AB  - Lenvatinib is an orally available multi-targeted tyrosine kinase inhibitor with
      anti-angiogenic and antitumor activity. To get more insight into the disposition
      of lenvatinib, a mass balance study was performed in patients with advanced solid
      tumors. A single oral 24 mg (100 MUCi) dose of (14)C-lenvatinib was administered
      to six patients, followed by collection of blood, plasma, urine and feces for 7
      to 10 days. The collected material was analyzed for total radioactivity,
      unchanged lenvatinib and selected metabolites. The safety and antitumor effect of
      a daily oral dose of 24 mg non-labeled lenvatinib were assessed in the extension
      phase of the study. Peak plasma concentrations of lenvatinib and total
      radioactivity were reached 1.6 and 1.4 h after administration, respectively, and
      their terminal phase half-lifes were 34.5 and 17.8 h, respectively. Unchanged
      lenvatinib systemic exposure accounted for 60 % of the total radioactivity in
      plasma. Peak concentrations of the analyzed metabolite were over 700-fold lower
      than the peak plasma concentration of lenvatinib. Ten days after the initial
      dose, the geometric mean (+/- CV) recovery of administered dose was 89 % +/-10 %,
      with 64 % +/-11 % recovered in feces and 25 % +/-18 % in urine. Unchanged
      lenvatinib in urine and feces accounted for 2.5 % +/-68 % of the administered
      dose, indicating a major role of metabolism in the elimination of lenvatinib. In
      conclusion, lenvatinib is rapidly absorbed and extensively metabolized, with
      subsequent excretion in urine and, more predominantly, in feces. Additionally,
      lenvatinib showed acceptable safety and preliminary antitumor activity.

PMID- 25377394
TI  - Opioid analgesia for acute abdominal pain in children: A systematic review and
      meta-analysis.
AB  - OBJECTIVES: There are long-held concerns that analgesia in patients with acute
      abdominal pain may obscure the physical examination and lead to missing a
      diagnosis of appendicitis. Despite evidence to the contrary, analgesia continues
      to be underutilized and suboptimally dosed in children with acute abdominal pain.
      The objective of this systematic review and meta-analysis was to determine if
      opioids provide analgesia without an increase in side effects and appendicitis
      related complications. METHODS: Trials were identified through electronic
      searches of MEDLINE (1946-2013), EMBASE (1980-2013), Cochrane Central Register of
      Controlled Trials (2013), CINAHL (1981-2013), and Google Scholar (2013). All
      randomized controlled trials (RCTs) of children aged 0-18 years with acute
      abdominal pain that compared any opioid analgesic to placebo were included. The
      methodologic qualities of studies and the overall quality of evidence were
      evaluated using the Cochrane Collaboration's Risk of Bias tool and the Grading of
      Recommendations Assessment, Development, and Evaluation system, respectively.
      RESULTS: Six RCTs met inclusion criteria, and each compared a single-dose
      parenteral opioid to a placebo, providing data on 342 children aged 5 to 18
      years. The pooled mean pre/post difference in self-reported pain scores was 19.61
      mm (95% confidence interval [CI] = -1.16 to 40.37 mm) lower in those receiving
      opioid analgesia. There was no significant increase in the risk of perforation or
      abscess associated with opioids in cases of appendicitis (relative risk [RR] =
      1.03, 95% CI = 0.55 to 1.93). The risk of side effects was significantly greater
      in patients who received opioids (RR = 6.06, 95% CI = 1.10 to 33.49).
      Subtherapeutic dosing of opioids was detected in all six trials. CONCLUSIONS: The
      use of opioids in undifferentiated acute abdominal pain in children is associated
      with no difference in pain scores and an increased risk of mild side effects.
      However, there is no increased risk of perforation or abscess. The overall
      quality of evidence is low, suggesting the need for larger, high-quality trials
      that are powered to detect both serious complications of appendicitis and
      determine the most efficacious opioid dosing for children.

PMID- 25377395
TI  - Low-dose ketamine improves pain relief in patients receiving intravenous opioids
      for acute pain in the emergency department: results of a randomized, double
      blind, clinical trial.
AB  - OBJECTIVES: Low-dose ketamine has been used perioperatively for pain control and
      may be a useful adjunct to intravenous (IV) opioids in the control of acute pain
      in the emergency department (ED). The aim of this study was to determine the
      effectiveness of low-dose ketamine as an adjunct to morphine versus standard care
      with morphine alone for the treatment of acute moderate to severe pain among ED
      patients. METHODS: A double-blind, randomized, placebo-controlled trial with
      three study groups was conducted at a large, urban academic ED over a 10-month
      period. Eligible patients were 18 to 65 years old with acute moderate to severe
      pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and
      pain duration < 7 days) who were deemed by their treating physician to require IV
      opioids. The three study groups were: 1) morphine and normal saline placebo
      (standard care group), 2) morphine and 0.15 mg/kg ketamine (group 1), or 3)
      morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60,
      and 120 minutes after study medication administration and received rescue
      analgesia as needed to target a 50% reduction in pain. The primary outcome
      measure of pain relief, or pain intensity reduction, was derived using the NRS
      and calculated as the summed pain-intensity (SPID) difference over 2 hours. The
      amount and timing of rescue opioid analgesia was evaluated as a secondary
      outcome. The occurrence of adverse events was also measured. RESULTS: Sixty
      patients were enrolled (n = 20 in each group). There were no differences between
      study groups with respect to age, sex, race/ethnicity, preenrollment analgesia,
      or baseline NRS. Over the 2-hour poststudy medication administration period, the
      SPIDs were higher (greater pain relief) for the ketamine study groups than the
      control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1
      7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p < 0.02). The SPIDs
      for the ketamine groups were similar (p < 0.46). When compared to standard care,
      group 2 sustained the reduction in pain intensity up to 2 hours, whereas group 1
      was similar to standard care by 2 hours. Similar numbers of patients received
      rescue analgesia: standard care group, seven of 20, 35%; group 1, four of 20,
      20%; and group 2, four of 20, 20% (p = 0.48). Among those receiving rescue
      analgesia, those in the standard care group received analgesia sooner than either
      low-dose ketamine group, on average. More participants in the low-dose ketamine
      groups reported dysphoria and dizziness. CONCLUSIONS: Low-dose ketamine is a
      viable analgesic adjunct to morphine for the treatment of moderate to severe
      acute pain. Dosing of 0.3 mg/kg is possibly more effective than 0.15 mg/kg, but
      may be associated with minor adverse events. Future studies should evaluate
      additional outcomes, optimum dosing, and use in specific populations.

PMID- 25377396
TI  - Intraosseous versus intravenous infusion of hydroxocobalamin for the treatment of
      acute severe cyanide toxicity in a Swine model.
AB  - OBJECTIVES: Easily administrated cyanide antidotes are needed for first
      responders, military troops, and emergency department staff after cyanide
      exposure in mass casualty incidents or due to smoke inhalation during fires
      involving many victims. Hydroxocobalamin has proven to be an effective antidote,
      but cannot be given intramuscularly because the volume of diluent needed is too
      large. Thus, intraosseous (IO) infusion may be an alternative, as it is simple
      and has been recommended for the administration of other resuscitation drugs. The
      primary objective of this study was to compare the efficacy of IO delivery of
      hydroxocobalamin to intravenous (IV) injection for the management of acute
      cyanide toxicity in a well-described porcine model. METHODS: Twenty-four swine
      (45 to 55 kg) were anesthetized, intubated, and instrumented with continuous mean
      arterial pressure (MAP) and cardiac output monitoring. Cyanide was continuously
      infused until severe hypotension (50% of baseline MAP), followed by IO or IV
      hydroxocobalamin treatment. Animals were randomly assigned to receive IV (150
      mg/kg) or IO (150 mg/kg) hydroxocobalamin and monitored for 60 minutes after
      start of antidotal infusion. The primary outcome measure was the change in MAP
      after antidotal treatment from onset of hypotension (time zero) to 60 minutes. A
      sample size of 12 animals per group was determined by group size analysis based
      on power of 80% to detect a one standard deviation of the mean MAP between the
      groups with an alpha of 0.05. Whole blood cyanide, lactate, pH, nitrotyrosine
      (nitric oxide marker) levels, cerebral and renal near infrared spectrometry
      (NIRS) oxygenation, and inflammatory markers were also measured. Repeated
      measures analysis of variance was used to determine statistically significant
      changes between groups over time. RESULTS: At baseline and at the point of
      hypotension, physiologic parameters were similar between groups. At the
      conclusion of the study, 10 out of 12 animals in the IV group and 10 out of 12 in
      IO group survived (p = 1.0). Both groups demonstrated a similar return to
      baseline MAP (p = 0.997). Cardiac output, oxygen saturation, and systemic
      vascular resistance were also found to be similar between groups (p > 0.4), and
      no difference was detected between bicarbonate, pH, and lactate levels (p > 0.8).
      Cyanide levels were undetectable after the hydroxocobalamin infusion throughout
      the study in both groups (p = 1.0). Cerebral and renal NIRS oxygenation decreased
      in parallel to MAP during cyanide infusion and increased after antidote infusion
      in both groups. Serum nitrotyrosine increased during cyanide infusion in all
      animals and then decreased in both study arms after hydroxocobalamin infusion (p
      > 0.5). Serum cytokines increased starting at cyanide infusion and no difference
      was detected between groups (tumor necrosis factor-alpha, interleukin [IL]-1beta,
      IL-6, and IL-10). CONCLUSIONS: The authors found no difference in the efficacy of
      IV versus IO hydroxocobalamin in the treatment of severe cyanide toxicity in a
      validated porcine model.

PMID- 25377397
TI  - Intravenous lipid emulsion therapy does not improve hypotension compared to
      sodium bicarbonate for tricyclic antidepressant toxicity: a randomized,
      controlled pilot study in a swine model.
AB  - OBJECTIVES: Tricyclic antidepressants (TCAs) are highly lipophilic medications
      used to treat posttraumatic stress disorder and chronic pain. Intravenous lipid
      emulsion (ILE) is a recent antidote for lipophilic drug overdose with unclear
      effectiveness. ILE has been studied in TCA overdose in small animals, and cases
      are reported in humans, but controlled studies in a larger animal model are
      lacking. Given the high lipophilicity of amitriptyline, a TCA, the hypothesis was
      that ILE would be more effective than the standard antidote sodium bicarbonate in
      improving amitriptyline-induced hypotension. The objective was to determine if
      ILE improved hypotension (defined by a mean arterial pressure [MAP] < 60%
      baseline) compared to sodium bicarbonate for amitriptyline overdose in a
      critically ill porcine model. METHODS: In this prospective, randomized,
      controlled trial, 24 female Sus scrofa swine weighing 45 to 55 kg were infused
      with amitriptyline at 0.5 mg/kg/min until the MAP reached 60% of baseline values.
      Animals were randomized to the experimental treatment group (ILE 7 mL/kg bolus,
      then 0.25 mL/kg/min) or the standard treatment group (sodium bicarbonate 2 mEq/kg
      plus an equal volume of saline). The primary outcome was a 50% improvement in MAP
      after ILE administration. We continuously monitored heart rate (HR), systolic
      blood pressure (sBP), MAP, and cardiac output. Electrocardiograms were recorded
      every 15 minutes. Serum pH, pCO2 , bicarbonate, lactate, and electrolytes were
      measured. Amitriptyline levels were measured by liquid chromatography/tandem mass
      spectrometry. Statistical methods used to detect a difference in MAP between the
      two treatment groups included repeated-measures analysis of variance, adjusted
      for treatment, time, and the interaction of treatment by time. A sample size of
      12 animals per group provided a power of 0.8 and an alpha of 0.05 to detect a 50%
      difference in MAP. RESULTS: There was no difference at baseline between ILE and
      sodium bicarbonate groups in mean HR, sBP, MAP, or cardiac output. Mean amounts
      of amitriptyline to reach hypotension and time to hypotension were similar
      between groups. After hypotension there was no difference between groups for mean
      HR, sBP, MAP, or cardiac output. The median time from hypotension to death was
      greater for the sodium bicarbonate group (10 minutes [IQR = 6 to 61 minutes] vs.
      5 minutes [IQR = 4.5 to 6 minutes] for the ILE group; p = 0.003), but overall
      survival was not different. One ILE and four sodium bicarbonate pigs survived.
      Additionally, no difference was detected in QRS intervals between the two groups.
      The mean (+/-SD) amitriptyline level in the lipid layer was 3.34 (+/-2.12)
      MUg/mL, and in the aqueous layer, 4.69 (+/-2.44) MUg/mL. The ILE fatty layer
      contained 38.2% of total measurable amitriptyline, while the aqueous layer
      contained 53.6%. CONCLUSIONS: Intravenous lipid emulsion treatment failed to
      improve amitriptyline-induced hypotension when compared to the standard treatment
      of sodium bicarbonate in a large animal model of severe TCA overdose. Larger
      groups with better survival may yield different results from the high mortality
      observed in this pilot study. Similar amounts of amitriptyline were found in the
      aqueous and lipid layers. These conclusions are limited to a single ILE regimen.

PMID- 25377398
TI  - The effect of fat emulsion on hemodynamics following treatment with propranolol
      and clonidine in anesthetized rats.
AB  - OBJECTIVES: There is evidence indicating that intravenous fatty emulsion (IFE) is
      beneficial in restoring circulatory function in certain types of drug overdose.
      The authors investigated the hemodynamic effects of IFE compared to epinephrine
      in rats treated with propranolol and clonidine. METHODS: Anesthetized male
      Sprague-Dawley rats were instrumented for measurement of hemodynamics. Rats were
      randomly assigned to one of six groups (n = 6-8), and each received a clonidine
      infusion (150 MUg/kg) or an equivalent volume of normal saline (0.9% NaCl) over 1
      hour. Each rat then received normal saline (1.0 mL/kg) or propranolol (15 to 20
      mg/kg). Thereafter, each rat received a dose of IFE (20% solution; 1.0 mL/kg) or
      epinephrine (2.0 MUg/kg) or an equivalent volume of normal saline (1.0 mL/kg).
      RESULTS: Propranolol alone or with clonidine significantly (p < 0.05) reduced a
      number of hemodynamic parameters (mean arterial pressure, 37% to 70%; heart rate,
      30% to 51%; cardiac contractility [dP/dtmax], 50% to 67%; and abdominal aortic
      blood flow, 50% to 83%), while increasing PR intervals (65% to 85%) and QTc
      intervals (26% to 64%). Saline and epinephrine treatment after propranolol and
      clonidine combined resulted in no survivors in saline and two out of six in
      epinephrine group. IFE resulted in significant survival (seven out of eight) for
      30 minutes in rats treated with propranolol alone, and propranolol combined with
      clonidine (seven out of eight). CONCLUSIONS: These data demonstrate that IFE is
      effective for resuscitating rats overdosed on propranolol combined with
      clonidine. The effect of IFF is unlikely due to a direct positive inotropic or
      chronotropic action on the myocardium. IFE is also more effective than
      epinephrine treatment in this paradigm.

PMID- 25377399
TI  - Effect of intubation for gamma-hydroxybutyric acid overdose on emergency
      department length of stay and hospital admission.
AB  - OBJECTIVES: The objective was to examine the effect of endotracheal intubation on
      emergency department (ED) length of stay (LOS) and admission rates for patients
      with gamma-hydroxybutyrate (GHB) overdose. METHODS: A 3-year retrospective
      electronic and paper audit of recreational drug presentations was carried out at
      two major inner-city EDs in Melbourne, Australia. Different GHB overdose
      management strategies exist at the respective audit sites, namely: 1) all
      patients with a Glasgow Coma Scale (GCS) score of 8 or less are intubated or 2)
      uncomplicated patients with GCS scores of 8 or less are managed without
      intubation (conservative management), unless further complications arise. This
      difference allows for comparison of the effects of intubation. All suspected GHB
      related cases (defined as cases where GHB or its analogs gamma-butyrolactone or
      1,4-butanediol were recorded) in which altered consciousness state was noted as a
      presenting symptom at triage were selected from all recreational drug-related
      presentations occurring between January 2008 and December 2010. The relationship
      between intubation and the primary outcome, ED LOS, was examined using robust
      regression after adjustment for potential confounders. The relationship between
      intubation and admission status (admission to hospital versus discharge) was also
      examined using logistic regression. RESULTS: After adjustment for potential
      confounders such as GCS score, intubation of GHB-related cases in the ED was
      associated with an increase in mean LOS of 41% (95% confidence interval [CI] =
      19% to 65%) and an increase in the odds of admission to hospital of 9.95 (95% CI
      = 2.36 to 41.88) at one hospital site, compared to conservative airway
      management. CONCLUSIONS: Conservative airway management (no intubation) is
      associated with shorter ED LOS in cases of uncomplicated GHB-related coma in the
      ED and may also be associated with lower admission rates for these patients.

PMID- 25377400
TI  - Patient and trauma center characteristics associated with helicopter emergency
      medical services transport for patients with minor injuries in the United States.
AB  - BACKGROUND: Helicopter emergency medical services (EMS) transport is expensive,
      and previous work has shown that cost-effective use of this resource is dependent
      on the proportion of minor injuries flown. To understand how overtriage to
      helicopter EMS versus ground EMS can be reduced, it is important to understand
      factors associated with helicopter transport of patients with minor injuries.
      OBJECTIVES: The aim was to characterize patient and hospital characteristics
      associated with helicopter transport of patients with minor injuries. METHODS:
      This was a retrospective analysis of adults >=18 years who were transported by
      helicopter to Level I/II trauma centers from 2009 through 2010 as identified in
      the National Trauma Data Bank. Minor injuries were defined as all injuries scored
      at an Abbreviated Injury Scale (AIS) score of <3. Patient and hospital
      characteristics associated of being flown with only minor injuries were compared
      in an unadjusted and adjusted fashion. Hierarchical, multivariate logistic
      regression was used to adjust for patient demographics, mechanism of injury,
      presenting physiology, injury severity, urban-rural location of injury, total EMS
      time, hospital characteristics, and region. RESULTS: A total of 24,812 records
      were identified, corresponding to 76,090 helicopter transports. The proportion of
      helicopter transports with only minor injuries was 36% (95% confidence interval
      [CI] = 34% to 39%). Patient characteristics associated with being flown with
      minor injuries included being uninsured (odds ratio [OR] = 1.36, 95% CI = 1.26 to
      1.47), injury by a fall (OR = 1.32, 95% CI = 1.20 to 1.45), or other penetrating
      trauma (OR = 2.52, 95% CI = 2.12 to 3.00). Being flown with minor injuries was
      more likely if the patient was transported to a trauma center that also received
      a high proportion of patients with minor injuries by ground EMS (OR = 1.89, 95%
      CI = 1.58 to 2.26) or a high proportion of EMS traffic by helicopter (OR = 1.35,
      95% CI = 1.02 to 1.78). No significant association with urban-rural scene
      location or EMS transport time was found. CONCLUSIONS: Better recognizing which
      patients with falls and penetrating trauma have serious injuries that could
      benefit from being flown may lead to the more cost-effective use of helicopter
      EMS. More research is needed to determine why patients without insurance, who are
      most at risk for high out-of-pocket expenses from helicopter EMS, are at higher
      risk for being flown when only having minor injuries. This suggests that
      interventions to optimize cost-effectiveness of helicopter transport will likely
      require an evaluation of helicopter triage guidelines in the context of regional
      and patient needs.

PMID- 25377401
TI  - Association between the seat belt sign and intra-abdominal injuries in children
      with blunt torso trauma in motor vehicle collisions.
AB  - OBJECTIVES: The objective was to determine the association between the abdominal
      seat belt sign and intra-abdominal injuries (IAIs) in children presenting to
      emergency departments with blunt torso trauma after motor vehicle collisions
      (MVCs). METHODS: This was a planned subgroup analysis of prospective data from a
      multicenter cohort study of children with blunt torso trauma after MVCs. Patient
      history and physical examination findings were documented before abdominal
      computed tomography (CT) or laparotomy. Seat belt sign was defined as a
      continuous area of erythema, ecchymosis, or abrasion across the abdomen secondary
      to a seat belt restraint. The relative risk (RR) of IAI with 95% confidence
      intervals (CIs) was calculated for children with seat belt signs compared to
      those without. The risk of IAI in those patients with seat belt sign who were
      without abdominal pain or tenderness, and with Glasgow Coma Scale (GCS) scores of
      14 or 15, was also calculated. RESULTS: A total of 3,740 children with seat belt
      sign documentation after blunt torso trauma in MVCs were enrolled; 585 (16%) had
      seat belt signs. Among the 1,864 children undergoing definitive abdominal testing
      (CT, laparotomy/laparoscopy, or autopsy), IAIs were more common in patients with
      seat belt signs than those without (19% vs. 12%; RR = 1.6, 95% CI = 1.3 to 2.1).
      This difference was primarily due to a greater risk of gastrointestinal injuries
      (hollow viscous or associated mesentery) in those with seat belt signs (11% vs.
      1%; RR = 9.4, 95% CI = 5.4 to 16.4). IAI was diagnosed in 11 of 194 patients
      (5.7%; 95% CI = 2.9% to 9.9%) with seat belt signs who did not have initial
      complaints of abdominal pain or tenderness and had GCS scores of 14 or 15.
      CONCLUSIONS: Patients with seat belt signs after MVCs are at greater risk of IAI
      than those without seat belt signs, predominately due to gastrointestinal
      injuries. Although IAIs are less common in alert patients with seat belt signs
      who do not have initial complaints of abdominal pain or tenderness, the risk of
      IAI is sufficient that additional evaluation such as observation, laboratory
      studies, and potentially abdominal CT scanning is generally necessary.

PMID- 25377402
TI  - Evaluating the Pediatric Early Warning Score (PEWS) system for admitted patients
      in the pediatric emergency department.
AB  - OBJECTIVES: The Pediatric Early Warning Score (PEWS) systems were developed to
      provide a reproducible assessment of a child's clinical status while
      hospitalized. Most studies investigating the PEWS evaluate its usefulness in the
      inpatient setting. Limited studies evaluate the effectiveness and integration of
      PEWS in the pediatric emergency department (ED). The goal of this study was to
      explore the test characteristics of an ED-assigned PEWS score for intensive care
      unit (ICU) admission or clinical deterioration in admitted patients. METHODS:
      This was a prospective 12-month observational study of patients, aged 0 to 21
      years, admitted from the ED of an urban, tertiary care children's hospital. ED
      nurses were instructed in PEWS assignment and electronic medical record (EMR)
      documentation. Interrater reliability between nurses was evaluated. PEWS scores
      were measured at initial assessment (P0) and time of admission (P1). Patients
      were stratified into outcome groups: those admitted to the ICU either from the ED
      or as transfers from the floor and those admitted to the floor only. Clinical
      deterioration was defined as transfer to the ICU within 6 hours or within 6 to 24
      hours of admission. PEWS scores and receiver operating characteristic (ROC)
      curves were compared for patients admitted to the floor, ICU, and with clinical
      deterioration. RESULTS: The authors evaluated 12,306 consecutively admitted
      patients, with 99% having a PEWS documented in the EMR. Interrater reliability
      was excellent (intraclass coefficient = 0.91). A total of 1,300 (10.6%) patients
      were admitted to the ICU and 11,066 (89.4%) were admitted to the floor. PEWS
      scores were higher for patients in the ICU group (P0 = 2.8, SD +/- 2.4; P1 = 3.2,
      SD +/- 2.4; p < 0.0001) versus floor patients (P0 = 0.7, SD +/- 1.2; P1 = 0.5, SD
      +/- 0.9; p < 0.0001). To predict the need for ICU admission, the optimal cutoff
      points on the ROC are P0 = 1 and P1 = 2, with areas under the ROC curve (AUCs) of
      0.79 and 0.86, respectively. The likelihood ratios (LRs) for these optimal cutoff
      points were as follows: P0 +LR = 2.5 (95% confidence interval [CI] = 2.4 to 2.6,
      p < 0.05), -LR = 0.32 (95% CI = 0.28 to 0.36, p < 0.05); and P1 +LR = 6.2 (95% CI
      = 5.8 to 6.6, p < 0.05), -LR = 0.32 (95% CI = 0.29 to 0.35, p < 0.05). For every
      unit increase in P0 and P1 , the odds of admission to the ICU were 1.9 times
      greater (95% CI = 1.8 to 1.9, p < 0.0001) and 2.9 times greater (95% CI = 2.7 to
      3.1, p < 0.0001) than to the floor. There were 89 patients in the clinical
      deterioration group, with 36 (0.3%) patients transferred to the ICU within 6
      hours of admission and 53 (0.4%) patients transferred within 6 to 24 hours. In
      this group, an elevated P0 and P1 were statistically associated with an increased
      risk of transfer with optimal cutoff points similar to above; however, there were
      poorer AUCs and test characteristics. CONCLUSIONS: A PEWS system was implemented
      in this pediatric ED with excellent data capture and nurse interrater
      reliability. The study found that an elevated PEWS is associated with need for
      ICU admission directly from the ED and as a transfer, but lacks the necessary
      test characteristics to be used independently in the ED environment.

PMID- 25377403
TI  - Comparison of PIRO, SOFA, and MEDS scores for predicting mortality in emergency
      department patients with severe sepsis and septic shock.
AB  - OBJECTIVES: The Predisposition Insult Response and Organ failure (PIRO) scoring
      system has been developed for use in the emergency department (ED) to risk
      stratify sepsis cases, but has not been well studied among high-risk patients
      with severe sepsis and septic shock. The PIRO score was compared with the
      Sequential Organ Failure Assessment (SOFA) and Mortality in ED Sepsis (MEDS)
      scores to predict mortality in ED patients with features suggesting severe sepsis
      or septic shock in the ED. METHODS: This was an analysis of sepsis patients
      enrolled in a prospective observational ED study of patients presenting with
      evidence of shock, hypoxemia, or other organ failure. PIRO, MEDS, and SOFA scores
      were calculated from ED data. Analysis compared areas under the receiver operator
      characteristic (ROC) curves for 30-day mortality. RESULTS: Of 240 enrolled
      patients, final diagnoses were septic shock in 128 (53%), severe sepsis without
      shock in 70 (29%), and infection with no organ dysfunction in 42 (18%). Forty
      eight (20%) patients died within 30 days of presentation. Area under the ROC
      curve (AUC) for mortality was 0.86 (95% confidence interval [CI] = 0.80 to 0.92)
      for PIRO, 0.81 (95% CI = 0.74 to 0.88) for MEDS, and 0.78 (95% CI = 0.71 to 0.87)
      for SOFA scores. Pairwise comparisons of the AUC were as follows: PIRO versus
      SOFA, p = 0.01; PIRO versus MEDS, p = 0.064; and MEDS versus SOFA; p = 0.37.
      Mortality increased with increasing PIRO scores: PIRO < 5, 0%; PIRO 5 to 9, 5%;
      PIRO 10 to 14, 5%; PIRO 15 to 19, 37%; and PIRO >= 20, 80% (p < 0.001). The MEDS
      score also showed increasing mortality with higher scores: MEDS < 5, 0%; MEDS 5
      to 7, 12%; MEDS 8 to 11, 15%; MEDS 12 to 14, 48%; and MEDS > 15, 65% (p < 0.001).
      CONCLUSIONS: The PIRO model, taking into account comorbidities and septic source
      as well as physiologic status, performed better than the SOFA score and similarly
      to the MEDS score for predicting mortality in ED patients with severe sepsis and
      septic shock. These findings have implications for identifying and managing high
      risk patients and for the design of clinical trials in sepsis.

PMID- 25377404
TI  - Computed tomography abnormalities and epidemiology of adult patients presenting
      with first seizure to the emergency department in Qatar.
AB  - OBJECTIVES: There is little information available from the Middle Eastern region
      on adult patients presenting with first seizure. The objectives of this study
      were to describe epidemiological characteristics of patients presenting to the
      emergency department (ED) in Doha, Qatar, with first seizure and to determine the
      incidence of computed tomographic (CT) scan abnormalities. METHODS: A
      retrospective cohort study was conducted on all adult patients with first seizure
      presenting to Hamad General Hospital ED over a 1-year period (June 2012 through
      May 2013). Electronic patient records were reviewed for demographics,
      neuroimaging, electroencephalography, laboratory test results, and medications
      administered. RESULTS: There were 439 patients who satisfied inclusion criteria.
      Patients were aged a mean of 35.3 years (95% confidence interval [CI] = 33.92 to
      36.69 years) with a male-to-female ratio of five to one. CT abnormalities were
      detected in 154 patients (35.3%; 95% CI = 30.81% to 39.82%). Out of reported
      abnormal scans, 14.7% patients had significant abnormalities such as
      neurocysticercosis (9.2%); brain metastasis and neoplasm (3.4%); and subarachnoid
      and subdural hemorrhage, cavernous sinus thrombosis, acute stroke, and brain
      edema (2.0%). None of the patients had any electrolyte abnormalities, and three
      patients had hypoglycemia. Patients with initial abnormal CT brain results were
      more likely to have recurrent seizures (OR = 1.65; 95% CI = 1.11 to 2.45) within
      6 months. CONCLUSIONS: Adults who presented with first seizure to the ED in Qatar
      had a young male predominance, and a high proportion of brain CT scans were
      reported as abnormal. It is recommended that all such patients in this population
      should undergo prompt CT scanning in the ED, but the utility of routine
      electrolyte tests requires further investigation.

PMID- 25377405
TI  - National Institutes of Health support for individual mentored career development
      grants in emergency medicine.
AB  - OBJECTIVES: Individual mentored career (K) awards made by the National Institutes
      of Health (NIH) are an important way for medical researchers to develop their
      research skills. This study determined the number of individual mentored (K)
      awards awarded to emergency medicine (EM) faculty over a 6-year period and
      compared it with six other specialties. METHODS: The NIH database of both
      submitted and funded K01, K08, and K23 applications was queried and crossed with
      the departmental affiliation of the principal investigator. The results were
      further analyzed with data from the Association of American Medical Colleges to
      determine the relationship between the number of awards and the size of the
      teaching and research faculty. RESULTS: From 2008 to 2013, there were a total of
      45 career development submissions from principal investigators affiliated with
      departments of EM. Of these, 27 (60%) were successful. This success rate is the
      third lowest of the seven specialties in this analysis. Emergency physicians
      submit relatively few grants compared to the size of their faculty, and the
      funding rate, $1,959 per EM resident, was the second lowest of the six
      specialties examined. CONCLUSIONS: Although success rates are reasonable, EM
      investigators submit very few individual mentored career development
      applications. They should take greater advantage of this mechanism to further
      their research training.

PMID- 25377406
TI  - Critical appraisal of emergency medicine education research: the best
      publications of 2013.
AB  - OBJECTIVES: The objective was to critically appraise and highlight
      methodologically superior medical education research articles published in 2013
      whose outcomes are pertinent to teaching and education in emergency medicine
      (EM). METHODS: A search of the English-language literature in 2013 querying
      Education Resources Information Center (ERIC), PsychINFO, PubMed, and Scopus
      identified 251 EM-related studies using hypothesis-testing or observational
      investigations of educational interventions. Two reviewers independently screened
      all of the publications and removed articles using established exclusion
      criteria. Six reviewers then independently scored the remaining 43 publications
      using either a qualitative a or quantitative scoring system, based on the
      research methodology of each article. Each scoring system consisted of nine
      criteria. Selected criteria were based on accepted educational review literature
      and chosen a priori. Both scoring systems used parallel scoring metrics and have
      been used previously within this annual review. RESULTS: Forty-three medical
      education research papers (37 quantitative and six qualitative studies) met the a
      priori criteria for inclusion and were reviewed. Six quantitative and one
      qualitative study were scored and ranked most highly by the reviewers as
      exemplary and are summarized in this article. CONCLUSIONS: This annual critical
      appraisal article aims to promote superior research in EM-related education, by
      reviewing and highlighting seven of 43 major education research studies, meeting
      a priori criteria, and published in 2013. Common methodologic pitfalls in the
      2013 papers are noted, and current trends in medical education research in EM are
      discussed.

PMID- 25377413
TI  - The perfect antidote.

PMID- 25377414
TI  - Flipping the bedside: telesonography and clinical education.

PMID- 25377415
TI  - First "glass" education: telementored cardiac ultrasonography using Google Glass-
      a pilot study.
AB  - OBJECTIVES: The objective of this study was to determine the feasibility of
      telementored instruction in bedside ultrasonography (US) using Google Glass. The
      authors sought to examine whether first-time US users could obtain adequate
      parasternal long axis (PSLA) views to approximate ejection fraction (EF) using
      Google Glass telementoring. METHODS: This was a prospective, randomized, single
      blinded study. Eighteen second-year medical students were randomized into three
      groups and tasked with obtaining PSLA cardiac imaging. Group A received real-time
      telementored education through Google Glass via Google Hangout from a remotely
      located expert. Group B received bedside education from the same expert. Group C
      represented the control and received no instruction. Each subject was given 3
      minutes to obtain a best PSLA cardiac imaging using a portable GE Vscan. Image
      clips obtained by each subject were stored. A second expert, blinded to
      instructional mode, evaluated images for adequacy and assigned an image quality
      rating on a 0 to 10 scale. RESULTS: Group A was able to obtain adequate images
      six out of six times (100%) with a median image quality rating of 7.5
      (interquartile range [IQR] = 6 to 10) out of 10. Group B was also able to obtain
      adequate views six out of six times (100%), with a median image quality rating of
      8 (IQR = 7 to 9). Group C was able to obtain adequate views one out of six times
      (17%), with a median image quality of 0 (IQR = 0 to 2). There were no
      statistically significant differences between Group A and Group B in the
      achievement of adequate images for E-point septal separation measurement or in
      image quality. CONCLUSIONS: In this pilot/feasibility study, novice US users were
      able to obtain adequate imaging to determine a healthy patient's EF through
      telementored education using Google Glass. These preliminary data suggest
      telementoring as an adequate means of medical education in bedside US. This
      conclusion will need to be validated with larger, more powerful studies including
      evaluation of pathologic findings and varying body habitus among models.

PMID- 25377416
TI  - Regarding: effects of emergency department expansion on emergency department
      patient flow.

PMID- 25377417
TI  - Regarding: effects of emergency department expansion on emergency department
      patient flow. In reply.

PMID- 25377418
TI  - Good study design, but flawed conclusion in emergency department tetracaine use.

PMID- 25377419
TI  - Good study design, but flawed conclusion in emergency department tetracaine use.
      In reply.

PMID- 25377420
TI  - Acute loss of Cited2 impairs Nanog expression and decreases self-renewal of mouse
      embryonic stem cells.
AB  - Identifying novel players of the pluripotency gene regulatory network centered on
      Oct4, Sox2, and Nanog as well as delineating the interactions within the complex
      network is key to understanding self-renewal and early cell fate commitment of
      embryonic stem cells (ESC). While overexpression of the transcriptional regulator
      Cited2 sustains ESC pluripotency, its role in ESC functions remains unclear.
      Here, we show that Cited2 is important for proliferation, survival, and self
      renewal of mouse ESC. We position Cited2 within the pluripotency gene regulatory
      network by defining Nanog, Tbx3, and Klf4 as its direct targets. We also
      demonstrate that the defects caused by Cited2 depletion are, at least in part,
      rescued by Nanog constitutive expression. Finally, we demonstrate that Cited2 is
      required for and enhances reprogramming of mouse embryonic fibroblasts to induced
      pluripotent stem cells.

PMID- 25377421
TI  - Bacillus Calmette-Guerin therapy in non-muscle-invasive bladder carcinoma after
      renal transplantation for end-stage aristolochic acid nephropathy.
AB  - Intravesical instillation of bacillus Calmette-Guerin (BCG) is the treatment of
      choice for non-muscle-invasive bladder cancer (NMIBC) of high grade and/or
      carcinoma in situ. This study evaluated the feasibility, efficacy, and tolerance
      of BCG instillations in eight kidney recipients for end-stage aristolochic acid
      nephropathy (AAN), a condition at high risk of urothelial carcinoma, and
      diagnosed for NMIBC. Five of them had relapsed after mitomycin C treatment.
      Tolerance to BCG was evaluated clinically and regular follow-up with fluorescence
      cystoscopy was performed along with renal graft function monitoring.
      Immunosuppression doses were adjusted and prophylactic anti-tuberculous treatment
      given to reduce risks of graft rejection and infection. After a mean follow-up
      period of 50 months, seven of the eight patients are free of relapse and kidney
      graft function remained unchanged. Tolerance was good, except for one episode of
      fever and one early discontinuation because of subjective discomfort. No systemic
      tuberculous infection was observed. This is the first clinical observation of
      successful BCG therapy for NMIBC in patients given transplant for end-stage AAN.
      Under standardized conditions, immunotherapy based on intravesical BCG is
      feasible, effective, and well tolerated in renal transplantation. 

PMID- 25377423
TI  - Highly fluorescent, photostable, and ultrasmall silicon drug nanocarriers for
      long-term tumor cell tracking and in-vivo cancer therapy.
AB  - Silicon nanoparticle (SiNP) nanocarriers feature strong fluorescence, ultrasmall
      size, robust photostability, and tunable drug-loading capacity. Using SiNP
      nanocarriers, the first example of long-term cancer cell tracking is successfully
      demonstrated. Furthermore, in vivo experiments show that tumor-bearing mice
      treated with SiNP nanocarriers survive over 20 d without observable tumor growth,
      demonstrating the high-efficacy chemotherapy of the Si nanocarriers. 

PMID- 25377422
TI  - Open challenges in magnetic drug targeting.
AB  - The principle of magnetic drug targeting, wherein therapy is attached to
      magnetically responsive carriers and magnetic fields are used to direct that
      therapy to disease locations, has been around for nearly two decades. Yet our
      ability to safely and effectively direct therapy to where it needs to go, for
      instance to deep tissue targets, remains limited. To date, magnetic targeting
      methods have not yet passed regulatory approval or reached clinical use. Below we
      outline key challenges to magnetic targeting, which include designing and
      selecting magnetic carriers for specific clinical indications, safely and
      effectively reaching targets behind tissue and anatomical barriers, real-time
      carrier imaging, and magnet design and control for deep and precise targeting.
      Addressing these challenges will require interactions across disciplines.
      Nanofabricators and chemists should work with biologists, mathematicians, and
      engineers to better understand how carriers move through live tissues and how to
      optimize carrier and magnet designs to better direct therapy to disease targets.
      Clinicians should be involved early on and throughout the whole process to ensure
      the methods that are being developed meet a compelling clinical need and will be
      practical in a clinical setting. Our hope is that highlighting these challenges
      will help researchers translate magnetic drug targeting from a novel concept to a
      clinically available treatment that can put therapy where it needs to go in human
      patients.

PMID- 25377424
TI  - Photodynamic Therapy and Its Role in Combined Modality Anticancer Treatment.
AB  - Photodynamic therapy (PDT) is a relatively new modality for anticancer treatment
      and although the interest has increased greatly in the recent years, it is still
      far from clinical routine. As PDT consists of administering a nontoxic
      photosensitizing chemical and subsequently illuminating the tumor with visible
      light, the treatment is not subject to dose-limiting toxicity, which is the case
      for established anticancer treatments like radiation therapy or chemotherapy.
      This makes PDT an attractive adjuvant therapy in a combined modality treatment
      regimen, as PDT provides an antitumor immune response through its ability to
      elicit the release of damage-associated molecular patterns and tumor antigens,
      thus providing an increased antitumor efficacy, potentially without increasing
      the risk of treatment-related toxicity. There is great interest in the elicited
      immune response after PDT and the potential of combining PDT with other forms of
      treatment to provide potent antitumor vaccines. This review summarizes recent
      studies investigating PDT as part of combined modality treatment, hopefully
      providing an accessible overview of the current knowledge that may act as a basis
      for new ideas or systematic evaluations of already promising results. 

PMID- 25377425
TI  - Interaction between NADPH-oxidase and Rho-kinase in angiotensin II-induced
      microglial activation.
AB  - Previous studies have shown that the brain renin-angiotensin system may play a
      major role, via angiotensin type 1 (AT1) receptors, in the regulation of
      neuroinflammation, oxidative stress and progression of dopaminergic degeneration.
      Angiotensin-induced activation of the microglial nicotinamide adenine
      dinucleotide phosphate (NADPH)-oxidase complex and microglial Rho-kinase are
      particularly important in this respect. However, it is not known whether
      crosstalk between Rho-kinase and NADPH-oxidase leads to microglial activation. In
      the present study, we found that, in the substantia nigra of rats, NADPH-oxidase
      activation was involved in angiotensin-induced Rho-kinase activation, which, in
      turn, was involved in angiotensin-induced NADPH-oxidase activation. In N9
      microglial cell line and primary microglial cultures, a crosstalk signaling
      between NADPH-oxidase and Rho-kinase occurred in a positive feedback fashion
      during angiotensin-induced microglial activation. Angiotensin-induced NADPH
      oxidase activation and superoxide generation led to NF-kB translocation and Rho
      kinase activation. Rho-kinase activation was involved in regulation of NADPH
      oxidase activation via p38 mitogen-activated protein kinase. Moreover, Rho-kinase
      activation, via NF-kB, upregulated AT1 receptor expression in microglial cells
      through a feed-forward mechanism. NADPH-oxidase and Rho-kinase pathways are known
      to be responsible for major components of the microglial response, such as
      changes involving microglial motility and phagocytosis, generation of superoxide,
      and release of inflammatory cytokines. The present results show that both
      pathways are linked by a common mechanism that may constitute a basic means of
      coordinating the microglial response.

PMID- 25377426
TI  - Development of a time-resolved fluorescence immunoassay for herpes simplex virus
      type 1 and type 2 IgG antibodies.
AB  - Enzyme-linked immunosorbent assays (ELISA) specific for anti-HSV glycoprotein G
      (gG) are most commonly used in the clinical diagnosis of HSV infection. But most
      of them are qualitative and with narrow detection ranges. A novel time-resolved
      fluoroimmunoassay (TRFIA) methodology was developed for the quantitative
      determination of HSV IgG in human serum. The assay was based on an indirect
      immunoassay format, and performed in 96-well microtiter plates. HSV-1 and HSV-2
      were used as the coating antigens. Eu(3+)-labeled goat anti-(human IgG)
      polyclonal antibodies were used as tracers. The fluorescence intensity of each
      well was measured and serum HSV IgG levels quantified against a calibration
      curve. The detection range of the novel TRFIA was between 5 and 500 AU/mL. Assay
      sensitivity was 0.568 AU/mL. The intra- and inter-assay coefficients of variation
      were 0.59-3.63% and 3.65-6.81%, respectively. Analytical recovery, dilution tests
      and serum panel tests were performed using TRFIA and the results proved
      satisfactory. There were no statistically significant differences in sensitivity
      and specificity between the TRFIA and commercial ELISAs. An effective, sensitive
      and accurate quantitative HSV type 1 and type 2 IgG TRFIA was successfully
      developed and provided diagnostic value in clinical use.

PMID- 25377427
TI  - Cardiomyocytes are Protected from Antiretroviral Nucleoside Analog-Induced
      Mitochondrial Toxicity by Overexpression of PGC-1alpha.
AB  - The nucleoside reverse transcriptase inhibitors (NRTIs), used for treatment of
      the human immunodeficiency virus-1, compromise mitochondria in cardiomyocytes and
      other host cells, limiting the clinical use of these drugs. To explore underlying
      mechanisms, we overexpressed PGC-1alpha, a master regulator of mitochondrial
      biogenesis, twofold in H9c2 rat cardiomyocyte cultures, hypothesizing that this
      might protect the mitochondria from damage induced by the NRTI combination
      zidovudine (AZT) and didanosine (ddI). The experimental groups, evaluated during
      16 passages (P) of drug exposure, included: PGC-1alpha-overexpressing cells with
      no exposure, or exposure to 50 uM AZT plus 50 uM ddI; and control cells with no
      exposure or exposure to the same doses of AZT and ddI. The AZT/ddI combination
      caused a growth inhibition of 15-20% in control cells, but none in PGC-1alpha
      cells. Apoptosis was highest in AZT/ddI-exposed control cells, and PGC-1alpha
      overexpression protected cells from AZT/ddI-induced apoptosis. At P3, P6, P8, and
      P12, uncoupled mitochondrial oxygen consumption rate, determined by Seahorse 24
      XF Analyzer, as higher in AZT/ddI-exposed PGC-1alpha cells, compared to AZT/ddI
      exposed control cells (p < 0.05 at all P). Complex I activity was higher in
      AZT/ddI-exposed PGC-1alpha overexpressing cells than that in AZT/ddI-exposed
      control cells (p < 0.05), and reactive oxygen species levels were lower in PGC
      1alpha overexpressing cells than that in control cells (p < 0.05) when both were
      exposed to AZT/ddI. Taken together, these experiments show proof of concept that
      overexpression of PGC-1alpha protects cardiomyocytes from NRTI-induced toxicity,
      and suggest that a pharmaceutical agent with similar activity may protect against
      NRTI-induced mitochondrial toxicity.

PMID- 25377428
TI  - Protective effect of apigenin on ischemia/reperfusion injury of the isolated rat
      heart.
AB  - Apigenin (Api), a mainly bioactive component of Apium graveolens L. var. dulce
      DC. (a traditional Chinese medicinal herb), possesses a wide range of biological
      activities, including antioxidant effects. It also has been shown to associate
      with lower prevalence of cardiovascular diseases, but its mechanisms of action
      remain unclear. The aim of the present study is to investigate the role of Api in
      isolated rat heart model of ischemia/reperfusion (I/R). Langendorff-perfused
      isolated rat hearts were used in our study. Api was added to the perfusate before
      ischemia and during reperfusion in the isolated pulsed rat heart exposed to 30
      min ischemia followed by 50-min reperfusion. The treatment with Api conferred a
      cardioprotective effect, and the treated hearts demonstrated an improved ischemic
      cardiac functional recovery, a decreased myocardial infarct size, a reduced
      activities of creatine kinase isoenzyme and lactate dehydrogenase in the coronary
      flow, a reduced number of apoptotic cardiomyocytes, a reduced activity of caspase
      3, up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the
      pro-apoptotic protein Bax. In addition, Api inhibited the phosphorylation of p38
      MAPKS during I/R. In conclusion, these observations provide preliminary evidence
      that Api can protect cardiomyocytes from I-/R-induced injury, at least partially,
      through the inhibition of p38 MAPKS signaling pathway. 

PMID- 25377429
TI  - Safety, tolerability, and pharmacokinetics of pregabalin in children with
      refractory partial seizures: a phase 1, randomized controlled study.
AB  - OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetics (PK) of
      pregabalin as adjunctive therapy in children with refractory partial seizures.
      METHODS: This was a phase 1, randomized, placebo-controlled, parallel-group,
      escalating-dose, multiple-dose study comprising a 7-day, double-blind treatment
      period and a single-blind, single dose of pregabalin administered to all children
      on day 8. Children in four age cohorts (1-23 months, 2-6, 7-11, and 12-16 years)
      received one of four doses of pregabalin (2.5, 5, 10, or 15 mg/kg/day) or
      placebo. Safety and tolerability were assessed throughout the study. Steady-state
      and single-dose PK parameters on day 8 were analyzed using standard
      noncompartmental procedures. RESULTS: Sixty-five children received at least one
      dose of treatment. Four pregabalin-treated children discontinued treatment, three
      of whom received 15 mg/kg/day. Two children experienced serious adverse events,
      one of whom received pregabalin 15 mg/kg/day. During double-blind treatment, the
      most common adverse events reported in the pregabalin-treated population were
      somnolence (27.1%) and dizziness (12.5%). Steady-state pregabalin peak and total
      exposure in each age cohort appeared to increase linearly with dose. Apparent
      oral clearance (CL/F) was directly related to creatinine clearance, consistent
      with adults. CL/F normalized for body weight was 43% higher in patients weighing
      <30 kg. Steady-state and single-dose PK were consistent. SIGNIFICANCE: Pregabalin
      at doses up to 10 mg/kg/day in children aged 1 month to 16 years, and at doses up
      to 15 mg/kg/day in those aged <6 years, demonstrated acceptable safety and
      tolerability. For children weighing <30 kg, a dose increase of 40% (mg/kg dosing)
      is required to achieve comparable exposure with adults or children weighing >=30
      kg. These data will inform dose selection in phase 3 trials of the efficacy and
      safety of adjunctive pregabalin in children with refractory partial seizures.

PMID- 25377430
TI  - Supramolecular water oxidation with Ru-bda-based catalysts.
AB  - Extremely slow and extremely fast new water oxidation catalysts based on the Ru
      bda (bda=2,2'-bipyridine-6,6'-dicarboxylate) systems are reported with turnover
      frequencies in the range of 1 and 900 cycles s(-1) , respectively. Detailed
      analyses of the main factors involved in the water oxidation reaction have been
      carried out and are based on a combination of reactivity tests, electrochemical
      experiments, and DFT calculations. These analyses give a convergent
      interpretation that generates a solid understanding of the main factors involved
      in the water oxidation reaction, which in turn allows the design of catalysts
      with very low energy barriers in all the steps involved in the water oxidation
      catalytic cycle. We show that for this type of system pi-stacking interactions
      are the key factors that influence reactivity and by adequately controlling them
      we can generate exceptionally fast water oxidation catalysts. 

PMID- 25377431
TI  - CW-laser-induced morphological changes of a single gold nanoparticle on glass:
      observation of surface evaporation.
AB  - Pulsed-laser heating of colloidal noble-metal nanoparticles in an aqueous
      solution induces morphological changes such as size reduction. However, the
      technique suffers disadvantages through polydispersed products. Here, we show
      that continuous-wave (CW) laser heating of single gold nanoparticles is capable
      of generating particles of smaller diameters with superb control in terms of
      exposure time and intensity. We show, based on calculations of particle
      temperatures under illumination, that surface evaporation below the boiling point
      of bulk gold occurs, resulting in a gradual diameter decrease in air. In our
      experiment, a focused illumination of Au NPs through an objective lens of a
      microscope provided peak-power densities (10(6)-10(7) W cm(-2)) equivalent to
      that of a typical nanosecond laser. Nevertheless the heating rate under CW laser
      illumination is much lower than that under pulsed-laser illumination, resulting
      in better control over nanoparticle heating and related morphological changes.
      Furthermore, the single-particle study of such heating helps us to clarify the
      evolution of such changes to a given particle. 

PMID- 25377432
TI  - Photodynamic therapy in the treatment of basal cell carcinoma: a systematic
      review and meta-analysis.
AB  - BACKGROUND/PURPOSE: This meta-analysis was designed to compare the efficacy,
      cosmetic outcome and safety of photodynamic therapy (PDT) with other procedures
      for the treatment of primary basal cell carcinoma (BCC). METHODS: A computerized
      search through electronic databases was performed to search for relevant
      randomized controlled trials (RCTs) published before October 2013. Only RCTs that
      compared PDT to non-PDT for patients with BCC were selected. The risk ratios
      (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Eight studies
      with a total of 1583 patients met the inclusion criteria. PDT was associated with
      lower complete clearance rate (RR: 0.93, 95% CI: 0.89-0.98), higher 1-year
      recurrence rate (RR: 12.42, 95% CI: 2.34-66.02) and 5-year recurrence rate (RR:
      6.79, 95% CI: 2.43-18.96) when compared with surgical excision. There was no
      statistically significant difference in complete clearance rate (RR: 0.92, 95%
      CI: 0.85-1.00), 1-year recurrence rate (RR: 1.04, 95% CI: 0.46 to 2.39) or 5-year
      recurrence rate (RR: 1.08, 95% CI: 0.62-1.86) when PDT was compared with
      cryotherapy. PDT had higher complete clearance rate compared with placebo but no
      statistically significant difference in complete clearance rate and 1-year
      recurrence rate when compared with pharmacologic treatment (topical imiquimod and
      5-fluorouracil). PDT had a significantly better cosmetic outcome than surgery and
      cryotherapy. CONCLUSIONS: PDT is a useful method for the treatment of BCC, more
      efficient than placebo and with a similar efficiency to cryosurgery and
      pharmacologic treatment. Even though it is less effective than surgical excision,
      PDT has cosmetic advantages over surgery and cryosurgery.

PMID- 25377433
TI  - Modelling releases of sterile mosquitoes with different strategies.
AB  - To prevent the transmissions of malaria, dengue fever, or other mosquito-borne
      diseases, one effective weapon is the sterile insect technique in which sterile
      mosquitoes are released to reduce or eradicate the wild mosquito population. To
      study the impact of the sterile insect technique on disease transmission, we
      formulate discrete-time mathematical models, based on difference equations, for
      the interactive dynamics of the wild and sterile mosquitoes, incorporating
      different strategies in releasing sterile mosquitoes. We investigate the model
      dynamics and compare the impact of the different release strategies. Numerical
      examples are given to demonstrate rich dynamical features of the models. 

PMID- 25377434
TI  - Hyalocytes in idiopathic epiretinal membranes: a correlative light and electron
      microscopic study.
AB  - PURPOSE: To describe characteristics of epiretinal cells at the vitreoretinal
      interface by correlative light and electron microscopy (CLEM). METHODS:
      Epiretinal membrane (ERM) specimens and internal limiting membrane (ILM)
      specimens were harvested by sequential peeling during vitrectomy from 27 eyes
      with idiopathic epiretinal gliosis, and processed for CLEM. Intraoperatively, the
      presence of posterior vitreous detachment (PVD) was documented. We used anti
      vimentin, anti-alpha-smooth muscle actin (alpha-SMA), and anti-CD45 as primary
      antibodies. A fluorescein-tagged immunonanogold cluster was used as secondary
      antibody and visualized under the fluorescence and transmission electron
      microscope. RESULTS: We demonstrated CD45-positive cells specifically labelled at
      their plasma membranes with ultrastructural features known for hyalocytes, such
      as oval nucleus with marginal chromatin, vacuoles, dense granules, and thin
      cytoplasmic protrusions. CD45-positive cells were mostly located on a thick layer
      of native vitreous collagen. They were covered by newly formed collagen strands
      with multilayered proliferation of myofibroblasts. We also demonstrated
      immunoreactivity for vimentin and alpha-SMA. Cell fragments with positive
      labelling for alpha-SMA and vimentin were not only found on the vitreal side of
      the ILM, but also on the retinal side. CONCLUSIONS: By CLEM, the majority of CD45
      positive cells in epiretinal cell proliferation were characterized as hyalocytes.
      In the context of anomalous PVD and vitreoschisis, ultrastructural features and
      topographic localization of hyalocytes suggest that these cells play a
      significant role in ERM formation. CLEM enables a more accurate characterization
      of epiretinal cell proliferation, and therefore, contributes to a better
      understanding of the pathogenesis of diseases at the vitreoretinal interface.

PMID- 25377435
TI  - Retrospective comparison of 25-gauge vitrectomy for repair of proliferative
      vitreoretinopathy with or without anterior proliferation.
AB  - PURPOSE: The purpose of the study was to compare the outcomes of 25-gauge
      vitrectomy for the repair of rhegmatogenous retinal detachment (RRD) complicated
      by proliferative vitreoretinopathy (PVR) with and without anterior PVR (A-PVR).
      METHODS: We reviewed the medical records of 26 eyes of 26 patients who underwent
      25-gauge vitrectomy for grade C PVR with A-PVR and 16 eyes of 16 patients who
      underwent the same procedure for grade C PVR without A-PVR. RESULTS: The number
      of previous surgeries for RRD was significantly higher in A-PVR cases than in
      those without A-PVR (P = 0.021). Scleral buckling and retinotomy/retinectomy were
      performed significantly more frequently in A-PVR eyes than in those without A-PVR
      (P = 0.017 and <0.001, respectively). The A-PVR eyes required longer surgical
      times than those without A-PVR (P =0.001). Final anatomical success was achieved
      in 24 of 26 (92.3 %) eyes with A-PVR and 16 of 16 (100 %) eyes without A-PVR (P
      =0.517). Best-corrected visual acuity before and six months after vitrectomy was
      1.41 +/- 0.96 and 0.86 +/- 0.78 logarithm of minimal angle of resolution (logMAR)
      units, respectively, in eyes with A-PVR and 1.17 +/- 0.87 and 0.63 +/- 0.72
      logMAR units, respectively, in eyes without A-PVR (P =0.355 and 0.276,
      respectively). CONCLUSIONS: These results indicate that 25-gauge vitrectomy can
      be used for both types of PVR, although eyes with A-PVR may require scleral
      buckling and retinotomy/retinectomy more often and may require longer surgical
      times.

PMID- 25377436
TI  - Thermal stress and predation risk trigger distinct transcriptomic responses in
      the intertidal snail Nucella lapillus.
AB  - Thermal stress and predation risk have profound effects on rocky shore organisms,
      triggering changes in their feeding behaviour, morphology and metabolism. Studies
      of thermal stress have shown that underpinning such changes in several intertidal
      species are specific shifts in gene and protein expression (e.g. upregulation of
      heat-shock proteins). But relatively few studies have examined genetic responses
      to predation risk. Here, we use next-generation RNA sequencing (RNA-seq) to
      examine the transcriptomic (mRNA) response of the snail Nucella lapillus to
      thermal stress and predation risk. We found that like other intertidal species,
      N. lapillus displays a pronounced genetic response to thermal stress by
      upregulating many heat-shock proteins and other molecular chaperones. In
      contrast, the presence of a crab predator (Carcinus maenas) triggered few
      significant changes in gene expression in our experiment, and this response
      showed no significant overlap with the snail's response to thermal stress. These
      different gene expression profiles suggest that thermal stress and predation risk
      could pose distinct and potentially additive challenges for N. lapillus and that
      genetic responses to biotic stresses such as predation risk might be more complex
      and less uniform across species than genetic responses to abiotic stresses such
      as thermal stress.

PMID- 25377437
TI  - Protective effects of resveratrol on postmenopausal osteoporosis: regulation of
      SIRT1-NF-kappaB signaling pathway.
AB  - Postmenopausal osteoporosis severely jeopardizes human health. Seeking for
      therapeutic drugs without side effects is of great necessity. Our study was
      designed to investigate whether resveratrol, an agonist of SIRT1, could have
      favorable effect on osteoporosis and to explore the underlying mechanisms. Rat
      osteoporosis model (ovariectomy group, OVX) was established by bilateral
      ovariectomy. Three different doses of resveratrol were used: 5 mg/kg/d (low
      dosed, RES(LD)), 25 mg/kg/d (medium-dosed, RES(MD)), and 45 mg/kg/d (high-dosed,
      RES(HD)). Results showed that RES(LD) did not show any significant effect on OVX
      alterations, while RES(MD) and RES(HD) significantly elevated the decreased bone
      mineral density induced by osteoporosis (RES(MD) 0.205 +/- 0.023, RES(HD) 0.214
      +/- 0.053 vs. OVX 0.165 +/- 0.050 g/cm(2) respectively; P < 0.05). Serum markers
      alkaline phosphatase (ALP) and osteocalcin were moderately restored by
      resveratrol. Moreover, resveratrol improved bone structure in OVX rats,
      demonstrated by hematoxylin-eosin staining and micro-computed tomographic
      results. In vitro results revealed that resveratrol promoted osteoblast
      differentiation of bone marrow mesenchymal stromal cells, evidenced by the
      increase of ALP generation and mRNA expression of collagen 1 (P < 0.05; RES(MD),
      RES(HD) vs. control group). SIRT1 gene silencing by siRNA transfection blocked
      these beneficial effects of resveratrol (P < 0.05; RES + SIRT1(KD) vs. RES(HD)).
      Western blot results showed that resveratrol activated SIRT1 and subsequently
      suppressed the activity of NF-kappaB with decreased expression level of p
      IkappaBalpha and NF-kappaB p65 (P < 0.05). Our findings verified the effects of
      specific dosed resveratrol on postmenopausal osteoporosis through osteoblast
      differentiation via SIRT1-NF-kappaB signaling pathway. This study suggested the
      therapeutic potential of resveratrol against osteoporosis and stressed the
      importance of effective doses.

PMID- 25377438
TI  - The immunologic and hematopoietic profiles of mesenchymal stem cells derived from
      different sections of human umbilical cord.
AB  - Mesenchymal stem cells (MSCs) have been widely used in allogeneic stem cell
      transplantation. We compared immunologic and hematopoietic characteristics of
      MSCs derived from whole human umbilical cord (UC), as well as from different
      sections of UCs, including the amniotic membrane (AM), Wharton's jelly (WJ), and
      umbilical vessel (UV). Cell phenotypes were examined by flow cytometry.
      Lymphocyte transformation test and mixed lymphocyte reaction were performed to
      evaluate the immuno-modulatory activity of MSCs derived from UCs. The mRNA
      expression of cytokines was detected by real-time polymerase chain reaction.
      Hematopoietic function was studied by co-culturing MSCs with CD34(+) cells
      isolated from cord blood. Our results showed that MSCs separated from these four
      different sections including UC, WJ, UV, and AM had similar biological
      characteristics. All of the MSCs had multi-lineage differentiation ability and
      were able to differentiate into osteoblasts, adipocytes, and chondrocytes. The
      MSCs also inhibited the proliferation of allogeneic T cells in a dose-dependent
      manner. The relative mRNA expression of cytokines was examined, and the results
      showed that UCMSCs had higher interleukin-6 (IL6), IL11, stem cell factor, and
      FLT3 expression than MSCs derived from specific sections of UCs. CD34(+) cells
      had high propagation efficiencies when co-cultured with MSCs derived from
      different sections of UCs, among which UCMSCs are the most efficient feeding
      layer. Our study demonstrated that MSCs could be isolated from whole UC or
      specific sections of UC with similar immunomodulation and hematopoiesis
      supporting characteristics. 

PMID- 25377439
TI  - Back to the future: a history of ACOG in social media's golden age.
AB  - PURPOSE OF REVIEW: To chronicle a medical professional society's adoption of
      innovation and to describe themes pertinent to the adoption. RECENT FINDINGS: In
      September 2013, the American College of Obstetricians and Gynecologists (ACOG)
      published a Committee Opinion on Toxic Environmental Agents that included an
      infographic and social media awareness campaign. To date, it claims one of the
      highest total audience reaches for an ACOG Facebook post reaching nearly 18 000
      viewers. Despite this powerful promise, ACOG's timely and successful social media
      campaign did not always appear an obvious strategy. Although social media took
      hold of popular culture in the early 2000s, social media's professional etiquette
      remained uncharted and rife, with cautionary tales through the latter half of the
      decade. SUMMARY: Through a thoughtful and dedicated process, the ACOG Fellow and
      Junior Fellow leadership partnered to navigate the appropriate balance of
      innovation and prudence that propelled ACOG into social media's golden age, and
      paved the pathway for more progressive institutional changes.

PMID- 25377441
TI  - Development and validation of the English Pain Interference Index and Pain
      Interference Index-Parent report.
AB  - OBJECTIVE: Measurement of pain interference in children is challenged by a lack
      of validated measures with a parent proxy report. This study investigated the
      psychometric properties of the Pain Interference Index (PII), a six-item
      questionnaire originally developed in Swedish, in chronically ill youth. METHODS:
      We adapted the PII for English-speaking participants and created a parallel
      parent proxy measure. Respondents indicate how much pain has interfered with the
      child's life in the past 2 weeks (0-6 scale); higher scores indicate more pain
      interference. Eligible participants included individuals 6-25 years with
      neurofibromatosis type 1 (NF1) and cancer. Internal consistency was assessed;
      validity was examined by correlating PII scores with existing measures of pain
      interference (Modified Brief Pain Inventory [MBPI]) and pain intensity (visual
      analogue scale [VAS]), and with measures of disease severity. RESULTS: Among 60
      participants (mean age 14.7 years, range 6-24) and their parents, PII internal
      consistency was 0.84 and 0.96, respectively. PII scores correlated with MBPI (r =
      0.81, P < 0.0001) and VAS (r = 0.55, P < 0.0001) scores and differentiated
      between patients with mild vs moderate/severe NF1 disease severity (P < 0.05).
      The PII-Parent was significantly correlated with the mothers' and fathers' VAS
      rating of the child's pain intensity (Ps < 0.01). CONCLUSIONS: Internal
      consistency of the English PII is high; validity is supported by the PII's
      correlations with other measures of pain interference and pain intensity, and
      with disease severity in patients with NF1. Preliminary data indicate that the
      English PII is a reliable, valid, feasible pain interference measure for youth
      with NF1 and cancer.

PMID- 25377442
TI  - Haemophilia Experiences, Results and Opportunities (HERO) study: treatment
      related characteristics of the population.
AB  - The HERO (Haemophilia Experiences, Results and Opportunities) quantitative
      surveys collected information on characteristics and perceptions of adult persons
      with haemophilia (PWH) and parents of children with haemophilia. The aim of this
      article is to describe the perceptions of PWH and parents on psychosocial aspects
      related to treatment. Two online surveys (one for PWH, one for parents) were
      conducted in 10 countries. Among 675 PWH respondents, 77% reported having
      responsibility for their own care; 72% of 561 parent respondents had the main
      responsibility for their son. PWH were most commonly treated on demand (45% of
      648 adults using factor concentrate), with 32% on regular prophylaxis and 23%
      treated on demand with short-term prophylaxis (e.g. for sports/physiotherapy).
      Children were most often treated with prophylaxis (65% of 549 children using
      factor concentrate), with 26% treated on demand and 8% treated on demand with
      short-term prophylaxis. Factor was generally used as instructed at home. Some
      respondents (41% PWH; 30% parents) had difficulties/concerns with factor
      availability/affordability. PWH reported more bleeds in the last 12 months than
      parents reporting their son's bleeds (mean 17.8 vs. 8.7). Both PWH and parents
      generally perceived that overall, their (their son's) haemophilia was well
      controlled. Results differed by country. The HERO study captured new, patient
      based data regarding many facets of life relevant to PWH, including treatment.
      The information conveyed in this article largely represents new insights
      regarding perceptions of treatment and provides initial benchmark statistics for
      further research.

PMID- 25377443
TI  - Longitudinal cerebral metabolic changes in pig-tailed macaques infected with the
      neurovirulent virus SIVsmmFGb.
AB  - Longitudinal cerebral metabolite changes in pig-tailed macaques inoculated with
      the simian immunodeficiency virus SIVsmmFGb were evaluated with in vivo proton
      MRS at 3 T. Blood sample collection, and MRS were carried out before and 2, 4, 8,
      12, 16, 20, and 24 weeks after SIV inoculation. Significant reduction of N
      acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in prefrontal
      gray matter (PGM) and glutamate/glutamine(Glx)/Cr ratio in striatum, and increase
      of myo-inositol (mI)/Cr in striatum were observed during acute SIV infection. The
      metabolite alterations during the SIVsmmFGb infection are largely in agreement
      with previous findings in other non-human primate models and HIV patients. Also,
      NAA/Cr in PGM and striatum and Glx/Cr in striatum are negatively correlated with
      the percentage of CD8+ T cells after the SIV infection, suggesting the
      interaction between brain metabolite and immune dysfunction. The present study
      complements previous studies by describing the time course of alterations of
      brain metabolites during SIVsmmFGb infection. The findings further demonstrate
      the efficacy of the SIVsmmFGb-infected macaque as a model to characterize central
      nervous system infection using novel neuroimaging approaches and also as a tool
      for exploration of novel and advanced neuroimaging techniques in HIV/AIDS
      studies.

PMID- 25377445
TI  - Cross-promotional alcohol discounting in Australia's grocery sector: a barrier to
      initiatives to curb excessive alcohol consumption?
AB  - OBJECTIVE: Excessive alcohol consumption is an increasing issue internationally.
      Pricing strategies, including discount restrictions, have been identified as one
      of the most effective policy means by which to reduce heavy alcohol consumption.
      In Australia, cross-promotional alcohol discounts are increasingly used by
      supermarket chains as a marketing tool. The purpose of the present study is to
      provide preliminary data on the nature and extent of cross-promotional alcohol
      discounting in the Australian grocery sector. METHODS: A purposive sample of 34
      supermarkets in Australia's three largest cities was selected and minor grocery
      purchases made to uncover the prevalence and level of cross-promotional alcohol
      discounting. RESULTS: Cross-promotional 'bundled' discounts were very common with
      33 of the 34 supermarkets offering a 'two for one' discount on bottles of wine.
      Even with minor purchases (mean purchase $1.35), the mean value of discounts
      received was substantial ($16.23). CONCLUSIONS: These results appear to be
      consistent with claims that major supermarket chains are using alcohol discounts
      as loss leaders to entice new consumers. IMPLICATIONS: These strategies are
      antithetical to public health strategies aimed at reducing excessive alcohol
      consumption. Further examination of the impact of major retailers on public
      health initiatives is warranted, particularly in light of increasing retailer
      concentration.

PMID- 25377446
TI  - Importance of Abdominal Ultrasound in 17 Patients with Histologically Confirmed
      Autoimmune Pancreatitis (AIP).
AB  - PURPOSE: Autoimmune pancreatitis (AIP) is an independent, underdiagnosed, rare
      form of chronic pancreatitis. The goal of this study is to document ultrasound
      findings in histologically confirmed AIP in order to determine the diagnostic
      value of ultrasound. MATERIALS AND METHODS: 6 of 74 DEGUM instructors for
      internal medicine (level 3 and 2) provided anonymized clinical and sonographic
      data from 17 patients with histologically confirmed AIP. RESULTS: 9/17 patients
      had diffuse AIP, 8/17 had focal AIP, 14/17 suffered from upper abdominal pain,
      9/17 had jaundice, and 3/9 had an elevated IgG4 level. Ultrasound showed diffuse
      hypoechoic organ enlargement in 9/17 cases and a hypoechoic tumor with an unclear
      border in 8/17 cases. AIP was verified by ultrasound-guided percutaneous core
      biopsy in 14 cases, by biopsy of the bile duct in 1 case, and by surgical biopsy
      in 2 cases. Involvement of the hepatobiliary system was present in 7/17 patients
      and autoimmune cholangitis was verified in 5 cases. All patients experienced
      remission after immunosuppressive treatment. The pancreatic duct had a normal
      width in 11 cases, was dilated in 5 cases, and was stenosed over a long stretch
      in 3 cases. Contrast-enhanced ultrasound did not show uniform signal increase but
      also no significantly reduced or absent perfusion. CONCLUSION: Ultrasound can be
      diagnostically useful if the clinical manifestations of AIP are known. While the
      diffuse form allows an ad-hoc suspected diagnosis, the focal form can only be
      suspected in the case of additional extrapancreatic involvement. Contrast
      enhanced ultrasound (CEUS) contributes greatly to the differentiation from ductal
      adenocarcinoma in the case of focal AIP.

PMID- 25377447
TI  - Evaluation of the chronic toxicity and carcinogenicity of perfluorohexanoic acid
      (PFHxA) in Sprague-Dawley rats.
AB  - Perfluorohexanoic acid (PFHxA), a 6-carbon perfluoroalkyl (C6; CAS # 307-24-4),
      has been proposed as a replacement for the commonly used 8-carbon
      perfluoroalkyls: perfluorooctanoic acid and perfluorooctane sulfonate. PFHxA is
      not currently a commercial product but rather the ultimate degradation product of
      C6 fluorotelomer used to make C6 fluorotelomer acrylate polymers. It can be
      expected that, to a greater or lesser extent, the environmental loading of PFHxA
      will increase, as C6 fluorotelomer acrylate treatments are used and waste is
      generated. This article reports on a chronic study (duration 104 weeks) that was
      performed to evaluate the possible toxicologic and carcinogenic effects of PFHxA
      in gavage (daily gavage, 7 days per week) treated male and female Sprague-Dawley
      (SD) rats. In the current study, dosage levels of 0, 2.5, 15, and 100 mg/kg/day
      of PFHxA (males) and 5, 30, and 200 mg/kg/day of PFHxA (females) were selected
      based on a previous subchronic investigation. No effects on body weights, food
      consumption, a functional observational battery, or motor activity were observed
      after exposure to PFHxA. While no difference in survival rates in males was seen,
      a dose-dependent decrease in survival in PFHxA-treated female rats was observed.
      Hematology and serum chemistry were unaffected by PFHxA. PFHxA-related histologic
      changes were noted in the kidneys of the 200-mg/kg/day group females. Finally,
      there was no evidence that PFHxA was tumorigenic in male or female SD rats at any
      of the dosage levels examined. 

PMID- 25377444
TI  - Impact of minocycline on cerebrospinal fluid markers of oxidative stress,
      neuronal injury, and inflammation in HIV-seropositive individuals with cognitive
      impairment.
AB  - Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress,
      neuronal injury, and inflammation and decreased neurotransmitter levels have been
      reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have
      a neuroprotective effect by inhibiting inducible nitric oxide synthase, which
      produces nitric oxide, a compound that induces oxygen free radical production. In
      A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of
      Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline
      was not associated with cognitive improvement, but the effect on the above CSF
      measures was not examined previously. The objective of this study was to examine
      the effect of minocycline on markers of oxidative stress, neuronal injury,
      neurotransmitter levels, and inflammation from CSF in participants in A5235. One
      hundred seven HIV+ individuals received either minocycline 100 mg or placebo
      orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional
      lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides
      and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine
      metabolites, neurofilament heavy chain, and inflammatory cytokines were measured
      in the CSF before and after treatment. The 24-week change in ceramides was larger
      in a beneficial direction in the minocycline group compared to the placebo group.
      The two groups did not differ in the 24-week changes for other markers.These
      results suggest that minocycline may decrease lipid markers of oxidative stress
      (ceramides) in individuals with HAND; however, an effect of minocycline on other
      CSF markers was not observed. A larger sample size is needed to further validate
      these results.

PMID- 25377448
TI  - Late-born intermittently fasted juvenile garden dormice use torpor to grow and
      fatten prior to hibernation: consequences for ageing processes.
AB  - Torpor is thought to slow age-related processes and to sustain growth and
      fattening of young individuals. Energy allocation into these processes represents
      a challenge for juveniles, especially for those born late in the season. We
      tested the hypothesis that late-born juvenile garden dormice (Eliomys quercinus)
      fed ad libitum ('AL', n = 9) or intermittently fasted ('IF', n = 9) use short
      torpor bouts to enhance growth and fat accumulation to survive winter. IF
      juveniles displayed more frequent and longer torpor bouts, compared with AL
      individuals before hibernation. Torpor frequency correlated negatively with
      energy expenditure and water turnover. Hence, IF juveniles gained mass at the
      same rate, reached similar pre-hibernation fattening and displayed identical
      hibernating patterns and mass losses as AL animals. We found no group differences
      in relative telomere length (RTL), an indicator of ageing, during the period of
      highest summer mass gain, despite greater torpor use by IF juveniles. Percentage
      change in RTL was negatively associated with mean and total euthermic durations
      among all individuals during hibernation. We conclude that torpor use promotes
      fattening in late-born juvenile dormice prior to hibernation. Furthermore, we
      provided the first evidence for a functional link between time spent in euthermy
      and ageing processes over winter. 

PMID- 25377449
TI  - Trunk orientation causes asymmetries in leg function in small bird terrestrial
      locomotion.
AB  - In contrast to the upright trunk in humans, trunk orientation in most birds is
      almost horizontal (pronograde). It is conceivable that the orientation of the
      heavy trunk strongly influences the dynamics of bipedal terrestrial locomotion.
      Here, we analyse for the first time the effects of a pronograde trunk orientation
      on leg function and stability during bipedal locomotion. For this, we first
      inferred the leg function and trunk control strategy applied by a generalized
      small bird during terrestrial locomotion by analysing synchronously recorded
      kinematic (three-dimensional X-ray videography) and kinetic (three-dimensional
      force measurement) quail locomotion data. Then, by simulating quail gaits using a
      simplistic bioinspired numerical model which made use of parameters obtained in
      in vivo experiments with real quail, we show that the observed asymmetric leg
      function (left-skewed ground reaction force and longer leg at touchdown than at
      lift-off) is necessary for pronograde steady-state locomotion. In addition,
      steady-state locomotion becomes stable for specific morphological parameters. For
      quail-like parameters, the most common stable solution is grounded running, a
      gait preferred by quail and most of the other small birds. We hypothesize that
      stability of bipedal locomotion is a functional demand that, depending on trunk
      orientation and centre of mass location, constrains basic hind limb morphology
      and function, such as leg length, leg stiffness and leg damping. 

PMID- 25377450
TI  - Cultural evolution of systematically structured behaviour in a non-human primate.
AB  - Culture pervades human life and is at the origin of the success of our species. A
      wide range of other animals have culture too, but often in a limited form that
      does not complexify through the gradual accumulation of innovations. We developed
      a new paradigm to study cultural evolution in primates in order to better
      evaluate our closest relatives' cultural capacities. Previous studies using
      transmission chain experimental paradigms, in which the behavioural output of one
      individual becomes the target behaviour for the next individual in the chain,
      show that cultural transmission can lead to the progressive emergence of
      systematically structured behaviours in humans. Inspired by this work, we
      combined a pattern reproduction task on touch screens with an iterated learning
      procedure to develop transmission chains of baboons (Papio papio). Using this
      procedure, we show that baboons can exhibit three fundamental aspects of human
      cultural evolution: a progressive increase in performance, the emergence of
      systematic structure and the presence of lineage specificity. Our results shed
      new light on human uniqueness: we share with our closest relatives essential
      capacities to produce human-like cultural evolution.

PMID- 25377451
TI  - Sex differences in developmental plasticity and canalization shape population
      divergence in mate preferences.
AB  - Sexual selection of high-quality mates can conflict with species recognition if
      traits that govern intraspecific mate preferences also influence interspecific
      recognition. This conflict might be resolved by developmental plasticity and
      learned mate preferences, which could drive preference divergence in populations
      that differ in local species composition. We integrate field and laboratory
      experiments on two calopterygid damselfly species with population genetic data to
      investigate how sex differences in developmental plasticity affect population
      divergence in the face of gene flow. Whereas male species recognition is fixed at
      emergence, females instead learn to recognize heterospecifics. Females are
      therefore more plastic in their mate preferences than males. We suggest that this
      results from sex differences in the balance between sexual selection for high
      quality mates and selection for species recognition. As a result of these sex
      differences, females develop more pronounced population divergence in their mate
      preferences compared with males. Local ecological community context and presence
      of heterospecifics in combination with sex differences in plasticity and
      canalization therefore shape population divergence in mate preferences. As
      ongoing environmental change and habitat fragmentation bring formerly allopatric
      species into secondary contact, developmental plasticity of mate preferences in
      either or both sexes might facilitate coexistence and prevent local species
      extinction.

PMID- 25377452
TI  - Sisters' curse: sexually antagonistic effects constrain the spread of a
      mitochondrial haplogroup superior in sperm competition.
AB  - Maternal inheritance of mitochondria creates a sex-specific selective sieve with
      implications for male longevity, disease susceptibility and infertility. Because
      males are an evolutionary dead end for mitochondria, mitochondrial mutations that
      are harmful or beneficial to males but not females cannot respond directly to
      selection. Although the importance of this male/female asymmetry in evolutionary
      response depends on the extent to which mitochondrial mutations exert
      antagonistic effects on male and female fitness, few studies have documented sex
      specific selection acting on mitochondria. Here, we exploited the discovery of
      two highly divergent mitochondrial haplogroups (A and B2) in central Panamanian
      populations of the pseudoscorpion Cordylochernes scorpioides. Next-generation
      sequencing and phylogenetic analyses suggest that selection on the ND4 and ND4L
      mitochondrial genes may partially explain sexually antagonistic mitochondrial
      effects on reproduction. Males carrying the rare B2 mitochondrial haplogroup
      enjoy a marked advantage in sperm competition, but B2 females are significantly
      less sexually receptive at second mating than A females. This reduced propensity
      for polyandry is likely to significantly reduce female lifetime reproductive
      success, thereby limiting the spread of the male beneficial B2 haplogroup. Our
      findings suggest that maternal inheritance of mitochondria and sexually
      antagonistic selection can constrain male adaptation and sexual selection in
      nature.

PMID- 25377454
TI  - A generalized sense of number.
AB  - Much evidence has accumulated to suggest that many animals, including young human
      infants, possess an abstract sense of approximate quantity, a number sense. Most
      research has concentrated on apparent numerosity of spatial arrays of dots or
      other objects, but a truly abstract sense of number should be capable of encoding
      the numerosity of any set of discrete elements, however displayed and in whatever
      sensory modality. Here, we use the psychophysical technique of adaptation to
      study the sense of number for serially presented items. We show that numerosity
      of both auditory and visual sequences is greatly affected by prior adaptation to
      slow or rapid sequences of events. The adaptation to visual stimuli was spatially
      selective (in external, not retinal coordinates), pointing to a sensory rather
      than cognitive process. However, adaptation generalized across modalities, from
      auditory to visual and vice versa. Adaptation also generalized across formats:
      adapting to sequential streams of flashes affected the perceived numerosity of
      spatial arrays. All these results point to a perceptual system that transcends
      vision and audition to encode an abstract sense of number in space and in time. 

PMID- 25377455
TI  - The reef-building coral Siderastrea siderea exhibits parabolic responses to ocean
      acidification and warming.
AB  - Anthropogenic increases in atmospheric CO2 over this century are predicted to
      cause global average surface ocean pH to decline by 0.1-0.3 pH units and sea
      surface temperature to increase by 1-4 degrees C. We conducted controlled
      laboratory experiments to investigate the impacts of CO2-induced ocean
      acidification (pCO2 = 324, 477, 604, 2553 uatm) and warming (25, 28, 32 degrees
      C) on the calcification rate of the zooxanthellate scleractinian coral
      Siderastrea siderea, a widespread, abundant and keystone reef-builder in the
      Caribbean Sea. We show that both acidification and warming cause a parabolic
      response in the calcification rate within this coral species. Moderate increases
      in pCO2 and warming, relative to near-present-day values, enhanced coral
      calcification, with calcification rates declining under the highest pCO2 and
      thermal conditions. Equivalent responses to acidification and warming were
      exhibited by colonies across reef zones and the parabolic nature of the corals'
      response to these stressors was evident across all three of the experiment's 30
      day observational intervals. Furthermore, the warming projected by the
      Intergovernmental Panel on Climate Change for the end of the twenty-first century
      caused a fivefold decrease in the rate of coral calcification, while the
      acidification projected for the same interval had no statistically significant
      impact on the calcification rate-suggesting that ocean warming poses a more
      immediate threat than acidification for this important coral species.

PMID- 25377456
TI  - A theoretical examination of the relative importance of evolution management and
      drug development for managing resistance.
AB  - Drug resistance is a serious public health problem that threatens to thwart our
      ability to treat many infectious diseases. Repeatedly, the introduction of new
      drugs has been followed by the evolution of resistance. In principle, there are
      two complementary ways to address this problem: (i) enhancing drug development
      and (ii) slowing the evolution of drug resistance through evolutionary
      management. Although these two strategies are not mutually exclusive, it is
      nevertheless worthwhile considering whether one might be inherently more
      effective than the other. We present a simple mathematical model that explores
      how interventions aimed at these two approaches affect the availability of
      effective drugs. Our results identify an interesting feature of evolution
      management that, all else equal, tends to make it more effective than enhancing
      drug development. Thus, although enhancing drug development will necessarily be a
      central part of addressing the problem of resistance, our results lend support to
      the idea that evolution management is probably a very significant component of
      the solution as well. 

PMID- 25377457
TI  - Spectral tuning by opsin coexpression in retinal regions that view different
      parts of the visual field.
AB  - Vision frequently mediates critical behaviours, and photoreceptors must respond
      to the light available to accomplish these tasks. Most photoreceptors are thought
      to contain a single visual pigment, an opsin protein bound to a chromophore,
      which together determine spectral sensitivity. Mechanisms of spectral tuning
      include altering the opsin, changing the chromophore and incorporating pre
      receptor filtering. A few exceptions to the use of a single visual pigment have
      been documented in which a single mature photoreceptor coexpresses opsins that
      form spectrally distinct visual pigments, and in these exceptions the functional
      significance of coexpression is unclear. Here we document for the first time
      photoreceptors coexpressing spectrally distinct opsin genes in a manner that
      tunes sensitivity to the light environment. Photoreceptors of the cichlid fish,
      Metriaclima zebra, mix different pairs of opsins in retinal regions that view
      distinct backgrounds. The mixing of visual pigments increases absorbance of the
      corresponding background, potentially aiding the detection of dark objects. Thus,
      opsin coexpression may be a novel mechanism of spectral tuning that could be
      useful for detecting prey, predators and mates. However, our calculations show
      that coexpression of some opsins can hinder colour discrimination, creating a
      trade-off between visual functions. 

PMID- 25377453
TI  - Multiple species of wild tree peonies gave rise to the 'king of flowers', Paeonia
      suffruticosa Andrews.
AB  - The origin of cultivated tree peonies, known as the 'king of flowers' in China
      for more than 1000 years, has attracted considerable interest, but remained
      unsolved. Here, we conducted phylogenetic analyses of explicitly sampled
      traditional cultivars of tree peonies and all wild species from the shrubby
      section Moutan of the genus Paeonia based on sequences of 14 fast-evolved
      chloroplast regions and 25 presumably single-copy nuclear markers identified from
      RNA-seq data. The phylogeny of the wild species inferred from the nuclear markers
      was fully resolved and largely congruent with morphology and classification. The
      incongruence between the nuclear and chloroplast trees suggested that there had
      been gene flow between the wild species. The comparison of nuclear and
      chloroplast phylogenies including cultivars showed that the cultivated tree
      peonies originated from homoploid hybridization among five wild species. Since
      the origin, thousands of cultivated varieties have spread worldwide, whereas four
      parental species are currently endangered or on the verge of extinction. The
      documentation of extensive homoploid hybridization involved in tree peony
      domestication provides new insights into the mechanisms underlying the origins of
      garden ornamentals and the way of preserving natural genetic resources through
      domestication. 

PMID- 25377459
TI  - Phylogenetic and functional dissimilarity does not increase during temporal
      heathland succession.
AB  - Succession has been a focal point of ecological research for over a century, but
      thus far has been poorly explored through the lens of modern phylogenetic and
      trait-based approaches to community assembly. The vast majority of studies
      conducted to date have comprised static analyses where communities are observed
      at a single snapshot in time. Long-term datasets present a vantage point to
      compare established and emerging theoretical predictions on the phylogenetic and
      functional trajectory of communities through succession. We investigated within,
      and between, community measures of phylogenetic and functional diversity in a
      fire-prone heathland along a 21 year time series. Contrary to widely held
      expectations that increased competition through succession should inhibit the
      coexistence of species with high niche overlap, plots became more
      phylogenetically and functionally clustered with time since fire. There were
      significant directional shifts in individual traits through time indicating
      deterministic successional processes associated with changing abiotic and/or
      biotic conditions. However, relative to the observed temporal rate of taxonomic
      turnover, both phylogenetic and functional turnover were comparatively low,
      suggesting a degree of functional redundancy among close relatives. These results
      contribute to an emerging body of evidence indicating that limits to the
      similarity of coexisting species are rarely observed at fine spatial scales. 

PMID- 25377458
TI  - The nutritionally responsive transcriptome of the polyphenic beetle Onthophagus
      taurus and the importance of sexual dimorphism and body region.
AB  - Developmental responses to nutritional variation represent one of the
      ecologically most important classes of adaptive plasticity. However, knowledge of
      genome-wide patterns of nutrition-responsive gene expression is limited. Here, we
      studied genome-wide transcriptional responses to nutritional variation and their
      dependency on trait and sex in the beetle Onthophagus taurus. We find that
      averaged across the transcriptome, nutrition contributes less to overall
      variation in gene expression than do sex or body region, but that for a modest
      subset of genes nutrition is by far the most important determinant of expression
      variation. Furthermore, our results reject the hypothesis that a common machinery
      may underlie nutrition-sensitive development across body regions. Instead, we
      find that magnitude (measured by number of differentially expressed contigs),
      composition (measured by functional enrichment) and evolutionary consequences
      (measured by patterns of sequence variation) are heavily dependent on exactly
      which body region is considered and the degree of sexual dimorphism observed on a
      morphological level. More generally, our findings illustrate that studies into
      the developmental mechanisms and evolutionary consequences of nutrition-biased
      gene expression must take into account the dynamics and complexities imposed by
      other sources of variation in gene expression such as sexual dimorphism and trait
      type.

PMID- 25377460
TI  - Examining predator-prey body size, trophic level and body mass across marine and
      terrestrial mammals.
AB  - Predator-prey relationships and trophic levels are indicators of community
      structure, and are important for monitoring ecosystem changes. Mammals colonized
      the marine environment on seven separate occasions, which resulted in differences
      in species' physiology, morphology and behaviour. It is likely that these changes
      have had a major effect upon predator-prey relationships and trophic position;
      however, the effect of environment is yet to be clarified. We compiled a dataset,
      based on the literature, to explore the relationship between body mass, trophic
      level and predator-prey ratio across terrestrial (n = 51) and marine (n = 56)
      mammals. We did not find the expected positive relationship between trophic level
      and body mass, but we did find that marine carnivores sit 1.3 trophic levels
      higher than terrestrial carnivores. Also, marine mammals are largely carnivorous
      and have significantly larger predator-prey ratios compared with their
      terrestrial counterparts. We propose that primary productivity, and its
      availability, is important for mammalian trophic structure and body size. Also,
      energy flow and community structure in the marine environment are influenced by
      differences in energy efficiency and increased food web stability. Enhancing our
      knowledge of feeding ecology in mammals has the potential to provide insights
      into the structure and functioning of marine and terrestrial communities. 

PMID- 25377461
TI  - The foraging benefits of being fat in a highly migratory marine mammal.
AB  - Foraging theory predicts that breath-hold divers adjust the time spent foraging
      at depth relative to the energetic cost of swimming, which varies with buoyancy
      (body density). However, the buoyancy of diving animals varies as a function of
      their body condition, and the effects of these changes on swimming costs and
      foraging behaviour have been poorly examined. A novel animal-borne accelerometer
      was developed that recorded the number of flipper strokes, which allowed us to
      monitor the number of strokes per metre swam (hereafter, referred to as strokes
      per-metre) by female northern elephant seals over their months-long, oceanic
      foraging migrations. As negatively buoyant seals increased their fat stores and
      buoyancy, the strokes-per-metre increased slightly in the buoyancy-aided
      direction (descending), but decreased significantly in the buoyancy-hindered
      direction (ascending), with associated changes in swim speed and gliding
      duration. Overall, the round-trip strokes-per-metre decreased and reached a
      minimum value when seals achieved neutral buoyancy. Consistent with foraging
      theory, seals stayed longer at foraging depths when their round-trip strokes-per
      metre was less. Therefore, neutrally buoyant divers gained an energetic advantage
      via reduced swimming costs, which resulted in an increase in time spent foraging
      at depth, suggesting a foraging benefit of being fat. 

PMID- 25377462
TI  - Serial founder effects and genetic differentiation during worldwide range
      expansion of monarch butterflies.
AB  - Range expansions can result in founder effects, increasing genetic
      differentiation between expanding populations and reducing genetic diversity
      along the expansion front. However, few studies have addressed these effects in
      long-distance migratory species, for which high dispersal ability might counter
      the effects of genetic drift. Monarchs (Danaus plexippus) are best known for
      undertaking a long-distance annual migration in North America, but have also
      dispersed around the world to form populations that do not migrate or travel only
      short distances. Here, we used microsatellite markers to assess genetic
      differentiation among 18 monarch populations and to determine worldwide
      colonization routes. Our results indicate that North American monarch populations
      connected by land show limited differentiation, probably because of the monarch's
      ability to migrate long distances. Conversely, we found high genetic
      differentiation between populations separated by large bodies of water. Moreover,
      we show evidence for serial founder effects across the Pacific, suggesting
      stepwise dispersal from a North American origin. These findings demonstrate that
      genetic drift played a major role in shaping allele frequencies and created
      genetic differentiation among newly formed populations. Thus, range expansion can
      give rise to genetic differentiation and declines in genetic diversity, even in
      highly mobile species.

PMID- 25377463
TI  - Natural allelic variations of xenobiotic-metabolizing enzymes affect sexual
      dimorphism in Oryzias latipes.
AB  - Sexual dimorphisms, which are phenotypic differences between males and females,
      are driven by sexual selection. Interestingly, sexually selected traits show
      geographical variations within species despite strong directional selective
      pressures. This paradox has eluded many evolutionary biologists for some time,
      and several models have been proposed (e.g. 'indicator model' and 'trade-off
      model'). However, disentangling which of these theories explains empirical
      patterns remains difficult, because genetic polymorphisms that cause variation in
      sexual differences are still unknown. In this study, we show that polymorphisms
      in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolizing enzyme, are
      associated with geographical differences in sexual dimorphism in the anal fin
      morphology of medaka fish (Oryzias latipes). Biochemical assays and genetic cross
      experiments show that high- and low-activity CYP1B1 alleles enhanced and declined
      sex differences in anal fin shapes, respectively. Behavioural and phylogenetic
      analyses suggest maintenance of the high-activity allele by sexual selection,
      whereas the low-activity allele possibly has experienced positive selection due
      to by-product effects of CYP1B1 in inferred ancestral populations. The present
      data can elucidate evolutionary mechanisms behind genetic variations in sexual
      dimorphism and indicate trade-off interactions between two distinct mechanisms
      acting on the two alleles with pleiotropic effects of xenobiotic-metabolizing
      enzymes.

PMID- 25377464
TI  - Costs and benefits of group living with disease: a case study of pneumonia in
      bighorn lambs (Ovis canadensis).
AB  - Group living facilitates pathogen transmission among social hosts, yet temporally
      stable host social organizations can actually limit transmission of some
      pathogens. When there are few between-subpopulation contacts for the duration of
      a disease event, transmission becomes localized to subpopulations. The number of
      per capita infectious contacts approaches the subpopulation size as pathogen
      infectiousness increases. Here, we illustrate that this is the case during
      epidemics of highly infectious pneumonia in bighorn lambs (Ovis canadensis). We
      classified individually marked bighorn ewes into disjoint seasonal
      subpopulations, and decomposed the variance in lamb survival to weaning into
      components associated with individual ewes, subpopulations, populations and
      years. During epidemics, lamb survival varied substantially more between ewe
      subpopulations than across populations or years, suggesting localized pathogen
      transmission. This pattern of lamb survival was not observed during years when
      disease was absent. Additionally, group sizes in ewe-subpopulations were
      independent of population size, but the number of ewe-subpopulations increased
      with population size. Consequently, although one might reasonably assume that
      force of infection for this highly communicable disease scales with population
      size, in fact, host social behaviour modulates transmission such that disease is
      frequency-dependent within populations, and some groups remain protected during
      epidemic events. 

PMID- 25377466
TI  - A proposed reinterpretation of Gerstmann's syndrome.
AB  - Gerstmann's syndrome includes the clinical tetrad of finger agnosia, agraphia,
      acalculia, and right-left confusion. Some disagreement remains with regard to the
      exact localization of the syndrome, but most probable it involves the left
      angular gyrus with a subcortical extension. Several authors have suggested that a
      defect in mental spatial rotations could simultaneously account for acalculia,
      right-left disorientation, and finger agnosia. It has been also suggested that
      semantic aphasia is always associated with acalculia; as a matter of fact, left
      angular gyrus has a significant involvement in semantic processing. In this
      paper, it is proposed that Gerstmann's syndrome should include: acalculia, finger
      agnosia, right-left disorientation, and semantic aphasia, but not agraphia. When
      the pathology extends toward the superior parietal gyrus, agraphia can be found.
      A fundamental defect (i.e., an impairment in verbally mediated spatial
      operations) could explain these apparently unrelated clinical signs. 

PMID- 25377465
TI  - Morphological patterns of the intraparietal sulcus and the anterior intermediate
      parietal sulcus of Jensen in the human brain.
AB  - Distinct parts of the intraparietal sulcal cortex contribute to sensorimotor
      integration and visual spatial attentional processing. A detailed examination of
      the morphological relations of the different segments of the complex
      intraparietal sulcal region in the human brain in standard stereotaxic space,
      which is a prerequisite for detailed structure-to-function studies, is not
      available. This study examined the intraparietal sulcus (IPS) and the related
      sulcus of Jensen in magnetic resonance imaging brain volumes registered in the
      Montreal Neurological Institute stereotaxic space. It was demonstrated that the
      IPS is divided into two branches: the anterior ramus and the posterior ramus of
      the IPS, often separated by a submerged gyral passage. The sulcus of Jensen
      emerges between the anterior and posterior rami of the IPS, and its ventral end
      is positioned between the first and second caudal branches of the superior
      temporal sulcus. In a small number of brains, the sulcus of Jensen may merge
      superficially with the first caudal branch of the superior temporal sulcus. The
      above morphological findings are discussed in relation to previously reported
      functional neuroimaging findings and provide the basis for future exploration of
      structure-to-function relations in the posterior parietal region of individual
      subjects. 

PMID- 25377467
TI  - Hepatitis C virus represses the cellular antiviral response by upregulating the
      expression of signal transducer and activator of transcription 3 through sponging
      microRNA-122.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that inhibit the expression of
      target protein coding genes at the post-transcriptional level. miR-122 is a liver
      specific miRNA. Notably, miR-122 is used by the hepatitis C virus (HCV) for
      triggering viral replication by interacting with the 5' untranslated region of
      the HCV RNA. The present study demonstrated that miR-122 inhibited the expression
      of signal transducer and activator of transcription 3 (STAT3), an antivirus
      response repressor. The HCV RNA acted as an 'miRNA sponge', which upregulated the
      expression of STAT3 by sealing miR-122. Subsequently, it was confirmed that this
      miR-122 sponge function of HCV RNA repressed the expression of polyinosinic
      polycytidylic acid-stimulated type I interferons. The present study provided a
      deeper understanding of the complex role of miR-122 in the progression of HCV
      infection and supported the miR-122 inhibition strategy in anti-HCV infection
      treatment.

PMID- 25377468
TI  - Microfluidic device for mechanical dissociation of cancer cell aggregates into
      single cells.
AB  - Tumors tissues house a diverse array of cell types, requiring powerful cell-based
      analysis methods to characterize cellular heterogeneity and identify rare cells.
      Tumor tissue is dissociated into single cells by treatment with proteolytic
      enzymes, followed by mechanical disruption using vortexing or pipetting. These
      procedures can be incomplete and require significant time, and the latter
      mechanical treatments are poorly defined and controlled. Here, we present a novel
      microfluidic device to improve mechanical dissociation of digested tissue and
      cell aggregates into single cells. The device design includes a network of
      branching channels that range in size from millimeters down to hundreds of
      microns. The channels also contain flow constrictions that generate well-defined
      regions of high shear force, which we refer to as "hydrodynamic micro-scalpels",
      to progressively disaggregate tissue fragments and clusters into single cells. We
      show using in vitro cancer cell models that the microfluidic device significantly
      enhances cell recovery in comparison to mechanical disruption by pipetting and
      vortexing after digestion with trypsin or incubation with EDTA. Notably, the
      device enabled superior results to be obtained after shorter proteolytic
      digestion times, resulting in fully viable cells in less than ten minutes. The
      device could also be operated under enzyme-free conditions that could better
      maintain expression of certain surface markers. The microfluidic format is
      advantageous because it enables application of well-defined mechanical forces and
      rapid processing times. Furthermore, it may be possible to directly integrate
      downstream processing and detection operations to create integrated cell-based
      analysis platforms. The enhanced capabilities enabled by our novel device may
      help promote applications of single cell detection and purification techniques to
      tumor tissue specimens, advancing the current understanding of cancer biology and
      enabling molecular diagnostics in clinical settings. 

PMID- 25377469
TI  - Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses
      in the solid tumor microenvironment.
AB  - High concentrations of adenosine in tumor microenvironments inhibit antitumor
      cytotoxic lymphocyte responses. Although T cells express inhibitory adenosine A2A
      receptors (A2AR) that suppress their activation and inhibit immune killing of
      tumors, a role for myeloid cell A2ARs in suppressing the immune response to
      tumors has yet to be investigated. In this study, we show that the growth of
      transplanted syngeneic B16F10 melanoma or Lewis lung carcinoma cells is slowed in
      Adora2a(f/f)-LysMCre(+/-) mice, which selectively lack myeloid A2ARs. Reduced
      melanoma growth is associated with significant increases in MHCII and IL12
      expression in tumor-associated macrophages and with >90% reductions in IL10
      expression in tumor-associated macrophages, dendritic cells (DC), and Ly6C(+) or
      Ly6G(+) myeloid-derived suppressor cells (MDSC). Myeloid deletion of A2ARs
      significantly increases CD44 expression on tumor-associated T cells and natural
      killer (NK) cells. Depletion of CD8(+) T cells or NK cells in tumor-bearing mice
      indicates that both cell types initially contribute to slowing melanoma growth in
      mice lacking myeloid A2A receptors, but tumor suppression mediated by CD8(+) T
      cells is more persistent. Myeloid-selective A2AR deletion significantly reduces
      lung metastasis of melanomas that express luciferase (for in vivo tracking) and
      ovalbumin (as a model antigen). Reduced metastasis is associated with increased
      numbers and activation of NK cells and antigen-specific CD8(+) T cells in lung
      infiltrates. Overall, the findings indicate that myeloid cell A2ARs have direct
      myelosuppressive effects that indirectly contribute to the suppression of T cells
      and NK cells in primary and metastatic tumor microenvironments. The results
      indicate that tumor-associated myeloid cells, including macrophages, DCs, and
      MDSCs all express immunosuppressive A2ARs that are potential targets of adenosine
      receptor blockers to enhance immune killing of tumors.

PMID- 25377470
TI  - Serine deprivation enhances antineoplastic activity of biguanides.
AB  - Metformin, a biguanide widely used in the treatment of type II diabetes, clearly
      exhibits antineoplastic activity in experimental models and has been reported to
      reduce cancer incidence in diabetics. There are ongoing clinical trials to
      evaluate its antitumor properties, which may relate to its fundamental activity
      as an inhibitor of oxidative phosphorylation. Here, we show that serine
      withdrawal increases the antineoplastic effects of phenformin (a potent biguanide
      structurally related to metformin). Serine synthesis was not inhibited by
      biguanides. Instead, metabolic studies indicated a requirement for serine to
      allow cells to compensate for biguanide-induced decrease in oxidative
      phosphorylation by upregulating glycolysis. Furthermore, serine deprivation
      modified the impact of metformin on the relative abundance of metabolites within
      the citric acid cycle. In mice, a serine-deficient diet reduced serine levels in
      tumors and significantly enhanced the tumor growth-inhibitory actions of
      biguanide treatment. Our results define a dietary manipulation that can enhance
      the efficacy of biguanides as antineoplastic agents that target cancer cell
      energy metabolism.

PMID- 25377471
TI  - Endothelin A receptor/beta-arrestin signaling to the Wnt pathway renders ovarian
      cancer cells resistant to chemotherapy.
AB  - The high mortality of epithelial ovarian cancer (EOC) is mainly caused by
      resistance to the available therapies. In EOC, the endothelin-1 (ET-1, EDN1)
      endothelin A receptor (ETAR, EDNRA) signaling axis regulates the epithelial
      mesenchymal transition (EMT) and a chemoresistant phenotype. However, there is a
      paucity of knowledge about how ET-1 mediates drug resistance. Here, we define a
      novel bypass mechanism through which ETAR/beta-arrestin-1 (beta-arr1, ARRB1)
      links Wnt signaling to acquire chemoresistant and EMT phenotype. We found that
      ETAR/beta-arr1 activity promoted nuclear complex with beta-catenin and p300,
      resulting in histone acetylation, chromatin reorganization, and enhanced
      transcription of genes, such as ET-1, enhancing the network that sustains
      chemoresistance. Silencing of beta-arr1 or pharmacologic treatment with the dual
      ETAR/ETBR antagonist macitentan prevented core complex formation and restored
      drug sensitivity, impairing the signaling pathways involved in cell survival,
      EMT, and invasion. In vivo macitentan treatment reduced tumor growth,
      vascularization, intravasation, and metastatic progression. The combination of
      macitentan and cisplatinum resulted in the potentiation of the cytotoxic effect,
      indicating that macitentan can enhance sensitivity to chemotherapy.
      Investigations in clinical specimens of chemoresistant EOC tissues confirmed
      increased recruitment of beta-arr1 and beta-catenin to ET-1 gene promoter. In
      these tissues, high expression of ETAR significantly associated with poor
      clinical outcome and chemoresistance. Collectively, our findings reveal the
      existence of a novel mechanism by which ETAR/beta-arr1 signaling is integrated
      with the Wnt/beta-catenin pathway to sustain chemoresistance in EOC, and they
      offer a solid rationale for clinical evaluation of macitentan in combination with
      chemotherapy to overcome chemoresistance in this setting.

PMID- 25377472
TI  - Mig-6 suppresses endometrial cancer associated with Pten deficiency and ERK
      activation.
AB  - PTEN mutations are the most common genetic alterations in endometrial cancer.
      Loss of PTEN and subsequent AKT activation stimulate estrogen receptor alpha
      dependent pathways that play an important role in endometrial tumorigenesis. The
      major pathologic phenomenon of endometrial cancer is the loss of ovarian steroid
      hormone control over uterine epithelial cell proliferation and apoptosis.
      However, the precise mechanism of PTEN/AKT signaling in endometrial cancer
      remains poorly understood. The progesterone signaling mediator MIG-6 suppresses
      estrogen signaling and it has been implicated previously as a tumor suppressor in
      endometrial cancer. In this study, we show that MIG-6 also acts as a tumor
      suppressor in endometrial cancers associated with PTEN deficiency. Transgenic
      mice, where Mig-6 was overexpressed in progesterone receptor-expressing cells,
      exhibited a relative reduction in uterine tumorigenesis caused by Pten
      deficiency. ERK1/2 was phosphorylated in uterine tumors and administration of an
      ERK1/2 inhibitor suppressed cancer progression in PR(cre/+)Pten(f/f) mice. In
      clinical specimens of endometrial cancer, MIG-6 expression correlated inversely
      with ERK1/2 phosphorylation during progression. Taken together, our findings
      suggest that Mig-6 regulates ERK1/2 phosphorylation and that it is crucial for
      progression of PTEN-mutant endometrial cancers, providing a mechanistic rationale
      for the evaluation of ERK1/2 inhibitors as a therapeutic treatment in human
      endometrial cancer.

PMID- 25377473
TI  - Mitochondrial MKP1 is a target for therapy-resistant HER2-positive breast cancer
      cells.
AB  - The MAPK phosphatase MKP1 (DUSP1) is overexpressed in many human cancers,
      including chemoresistant and radioresistant breast cancer cells, but its
      functional contributions in these settings are unclear. Here, we report that
      after cell irradiation, MKP1 translocates into mitochondria, where it prevents
      apoptotic induction by limiting accumulation of phosphorylated active forms of
      the stress kinase JNK. Increased levels of mitochondrial MKP1 after irradiation
      occurred in the mitochondrial inner membrane space. Notably, cell survival
      regulated by mitochondrial MKP1 was responsible for conferring radioresistance in
      HER2-overexpressing breast cancer cells, due to the fact that MKP1 serves as a
      major downstream effector in the HER2-activated RAF-MEK-ERK pathway. Clinically,
      we documented MKP1 expression exclusively in HER2-positive breast tumors,
      relative to normal adjacent tissue from the same patients. MKP1 overexpression
      was also detected in irradiated HER2-positive breast cancer stem-like cells
      (HER2(+)/CD44(+)/CD24(-/low)) isolated from a radioresistant breast cancer cell
      population after long-term radiation treatment. MKP1 silencing reduced clonogenic
      survival and enhanced radiosensitivity in these stem-like cells. Combined
      inhibition of MKP1 and HER2 enhanced cell killing in breast cancer. Together, our
      findings identify a new mechanism of resistance in breast tumors and reveal MKP1
      as a novel therapeutic target for radiosensitization.

PMID- 25377475
TI  - A meta-analysis of association between cerebral microbleeds and cognitive
      impairment.
AB  - BACKGROUND: The clinical effect of cerebral microbleeds (CMBs) on cognition has
      been receiving much research attention, but results are often inconsistent.
      MATERIAL/METHODS: We searched PubMed, Embase, Web of Science, and some Chinese
      electronic databases. A total of 15 studies were included. RESULTS: Patients with
      CMBs had higher incidence of cognitive dysfunction (OR 3.14; 95% CI 1.66-5.92)
      and lower scores of cognitive function (SMD was -0.36 [-0.55, -0.18] in the MMSE
      group and -0.65 [-0.99, -0.32] in the MoCA [Montreal Cognitive Assessment]
      group). The results also indicated that a higher number of CMB lesions led to
      more severe cognitive dysfunction (SMD was -2.41 [-5.04, -0.21] in the mild group
      and -2.75 [-3.50, -2.01] in the severe group). We also found that cognitive
      performance was significantly impaired when CMBs were located in deep (-0.4 [
      0.69, -0.11]), lobar regions (-0.50 [-0.92, -0.09]), basal ganglia (-0.72 [-1.03,
      -0.41]), and thalamus brain regions (-0.65 [-0.98, -0.32]). CONCLUSIONS: This
      meta-analysis showed that CMBs were associated with cognitive dysfunction
      according to higher number and different locations of CMBs. Future work should
      focus on long-term prognosis of continuing cognitive decline and specific
      treatments to reduce the formation of CMBs.

PMID- 25377476
TI  - Comparative attributional life cycle assessment of annual and perennial
      lignocellulosic feedstocks production under Mediterranean climate for biorefinery
      framework.
AB  - Annual fiber sorghum (FS) and perennial giant reed (GR) cultivated in the
      Mediterranean area are interesting due to their high productivity under drought
      conditions and their potential use as lignocellulosic feedstock for biorefinery
      purposes. This study compares environmental constraints related to FS and GR
      produced on experimental farms (in the Campania region) using an attributional
      life cycle assessment (LCA) approach through appropriate modeling of the
      perennial cultivation. For both crops, primary data were available for
      agricultural management. Direct field emissions (DFEs) were computed, including
      the potential soil carbon storage (SCS). Giant reed showed the lowest burdens for
      all impact categories analyzed (most were in the range of 40%-80% of FS values).
      More apparent were the differences for climate change and freshwater
      eutrophication (respectively 80% and 81% lower for GR compared to FS). These
      results are due to the short-term SCS, experimentally detected in the perennial
      GR crop (about 0.25 ton C ha(-1) yr(-1), with a global warming offsetting
      potential of about 0.03 ton CO2/ton(GR dry biomass)). The results are also due to
      the annual application of triple superphosphate at the sowing fertilization phase
      for FS, which occurs differently than it does for GR. Phosphorous fertilization
      was performed only when crops were being established and therefore properly
      spread along the overall crop lifetime. For both crops, after normalization,
      terrestrial acidification and particulate matter formation were relevant impact
      categories, as a consequence of the NH3 DFE by volatilization after urea were
      spread superficially. Therefore, the results suggest higher environmental
      benefits of the perennial crop than the annual crop.

PMID- 25377474
TI  - PELP1 overexpression in the mouse mammary gland results in the development of
      hyperplasia and carcinoma.
AB  - Estrogen receptor (ER) coregulator overexpression promotes carcinogenesis and/or
      progression of endocrine related-cancers in which steroid hormones are powerful
      mitogenic agents. Recent studies in our laboratory, as well as others,
      demonstrated that the estrogen receptor coregulator PELP1 is a proto-oncogene.
      PELP1 interactions with histone demethylase KDM1 play a critical role in its
      oncogenic functions and PELP1 is a prognostic indicator of decreased survival in
      patients with breast cancer. However, the in vivo significance of PELP1
      deregulation during initiation and progression of breast cancer remains unknown.
      We generated an inducible, mammary gland-specific PELP1-expressing transgenic
      (Tg) mouse (MMTVrtTA-TetOPELP1). We found more proliferation, extensive side
      branching, and precocious differentiation in PELP1-overexpressing mammary glands
      than in control glands. Aged MMTVrtTA-TetOPELP1 Tg mice had hyperplasia and
      preneoplastic changes as early as 12 weeks, and ER-positive mammary tumors
      occurred at a latency of 14 to 16 months. Mechanistic studies revealed that PELP1
      deregulation altered expression of a number of known ER target genes involved in
      cellular proliferation (cyclin D1, CDKs) and morphogenesis (EGFR, MMPs) and such
      changes facilitated altered mammary gland morphogenesis and tumor progression.
      Furthermore, PELP1 was hyper-phosphorylated at its CDK phosphorylation site,
      suggesting an autocrine loop involving the CDK-cyclin D1-PELP1 axis in promoting
      mammary tumorigenesis. Treatment of PELP1 Tg mice with a KDM1 inhibitor
      significantly reduced PELP1-driven hyperbranching, reversed alterations in cyclin
      D1 expression levels, and reduced CDK-driven PELP1 phosphorylation. These results
      further support the hypothesis that PELP1 deregulation has the potential to
      promote breast tumorigenesis in vivo and represent a novel model for future
      investigation into molecular mechanisms of PELP1-mediated tumorigenesis.

PMID- 25377477
TI  - From adverse drug event detection to prevention. A novel clinical decision
      support framework for medication safety.
AB  - BACKGROUND: Errors related to medication seriously affect patient safety and the
      quality of healthcare. It has been widely argued that various types of such
      errors may be prevented by introducing Clinical Decision Support Systems (CDSSs)
      at the point of care. OBJECTIVES: Although significant research has been
      conducted in the field, still medication safety is a crucial issue, while few
      research outcomes are mature enough to be considered for use in actual clinical
      settings. In this paper, we present a clinical decision support framework
      targeting medication safety with major focus on adverse drug event (ADE)
      prevention. METHODS: The novelty of the framework lies in its design that
      approaches the problem holistically, i.e., starting from knowledge discovery to
      provide reliable numbers about ADEs per hospital or medical unit to describe
      their consequences and probable causes, and next employing the acquired knowledge
      for decision support services development and deployment. Major design features
      of the framework's services are: a) their adaptation to the context of care (i.e.
      patient characteristics, place of care, and significance of ADEs), and b) their
      straightforward integration in the healthcare information technologies (IT)
      infrastructure thanks to the adoption of a service-oriented architecture (SOA)
      and relevant standards. RESULTS: Our results illustrate the successful
      interoperability of the framework with two commercially available IT products,
      i.e., a Computerized Physician Order Entry (CPOE) and an Electronic Health Record
      (EHR) system, respectively, along with a Web prototype that is independent of
      existing healthcare IT products. The conducted clinical validation with domain
      experts and test cases illustrates that the impact of the framework is expected
      to be major, with respect to patient safety, and towards introducing the CDSS
      functionality in practical use. CONCLUSIONS: This study illustrates an important
      potential for the applicability of the presented framework in delivering
      contextualized decision support services at the point of care and for making a
      substantial contribution towards ADE prevention. Nonetheless, further research is
      required in order to quantitatively and thoroughly assess its impact in
      medication safety.

PMID- 25377478
TI  - Oxygen- and temperature-dependent expression of survival protein kinases in
      crucian carp (Carassius carassius) heart and brain.
AB  - Living without oxygen is limited to very few vertebrates, one species being the
      fresh water fish crucian carp (Carassius carassius), which can survive months of
      anoxia at low temperatures. Mammalian heart and brain are particularly intolerant
      to oxygen deprivation, yet these organs can be conditioned to display increased
      resistance, possibly due to activation of several protein kinases. We
      hypothesized increased phosphorylation status of these kinases in hypoxic and
      anoxic crucian carp heart and brain. Moreover, we wanted to investigate whether
      the kinases showing the strongest phosphorylation during hypoxia/anoxia, ERK 1/2,
      p38-MAPK, JNK, PKCepsilon, and PKCdelta, also had increased expression and
      phosphorylation at cold temperatures, to better cope with the anoxic periods
      during winter. We found small differences in the phosphorylation status of ERK
      1/2, p38-MAPK, JNK, PKCepsilon, and PKCdelta during 10 days of severe hypoxia in
      both heart and brain (0.3 mg O2/l) and varying responses to reoxygenation. In
      contrast, 7 days of anoxia (<0.01 mg O2/l) markedly increased phosphorylation of
      ERK 1/2, p38-MAPK, JNK in the heart, and p38-MAPK and PKCepsilon in the brain.
      Similarly, varying acclimation temperature between 4, 10 and 20 degrees C induced
      large changes in phosphorylation status. Total protein expression in heart and
      brain neither changed during different oxygen regimes nor with different
      acclimation temperatures, except for ERK 1/2, which slightly decreased in the
      heart at 4 degrees C compared with 20 degrees C. A phylogenetic analysis
      confirmed that these protein kinases are evolutionarily conserved across a wide
      range of vertebrate species. Our findings indicate important roles of several
      protein kinases during oxygen deprivation.

PMID- 25377479
TI  - The calcium stored in the sarcoplasmic reticulum acts as a safety mechanism in
      rainbow trout heart.
AB  - Cardiomyocyte contraction depends on rapid changes in intracellular Ca(2+). In
      mammals, Ca(2+) influx as L-type Ca(2+) current (ICa) triggers the release of
      Ca(2+) from sarcoplasmic reticulum (SR) and Ca(2+)-induced Ca(2+) release (CICR)
      is critical for excitation-contraction coupling. In fish, the relative
      contribution of external and internal Ca(2+) is unclear. Here, we characterized
      the role of ICa to trigger SR Ca(2+) release in rainbow trout ventricular
      myocytes using ICa regulation by Ca(2+) as an index of CICR. ICa was recorded
      with a slow (EGTA) or fast (BAPTA) Ca(2+) chelator in control and isoproterenol
      conditions. In the absence of beta-adrenergic stimulation, the rate of ICa
      inactivation was not significantly different in EGTA and BAPTA (27.1 +/- 1.8 vs.
      30.3 +/- 2.4 ms), whereas with isoproterenol (1 MUM), inactivation was
      significantly faster with EGTA (11.6 +/- 1.7 vs. 27.3 +/- 1.6 ms). When barium
      was the charge carrier, inactivation was significantly slower in both conditions
      (61.9 +/- 6.1 vs. 68.0 +/- 8.7 ms, control, isoproterenol). Quantification
      revealed that without isoproterenol, only 39% of ICa inactivation was due to
      Ca(2+), while with isoproterenol, inactivation was Ca(2+)-dependent (~65%) and
      highly reliant on SR Ca(2+) (~46%). Thus, SR Ca(2+) is not released in basal
      conditions, and ICa is the main trigger of contraction, whereas during a stress
      response, SR Ca(2+) is an important source of cytosolic Ca(2+). This was not
      attributed to differences in SR Ca(2+) load because caffeine-induced transients
      were not different in both conditions. Therefore, Ca(2+) stored in SR of trout
      cardiomyocytes may act as a safety mechanism, allowing greater contraction when
      higher contractility is required, such as stress or exercise. 

PMID- 25377480
TI  - Disturbed flow induces systemic changes in metabolites in mouse plasma: a
      metabolomics study using ApoE-/- mice with partial carotid ligation.
AB  - Disturbed blood flow (d-flow) occurring in branched and curved arteries promotes
      endothelial dysfunction and atherosclerosis, in part, by altering gene expression
      and epigenomic profiles in endothelial cells. While a systemic metabolic change
      is known to play a role in atherosclerosis, it is unclear whether it can be
      regulated by local d-flow. Here, we tested this hypothesis by carrying out a
      metabolomics study using blood plasma samples obtained from ApoE(-/-) mice that
      underwent a partial carotid ligation surgery to induce d-flow. Mice receiving
      sham ligation were used as a control. To study early metabolic changes, samples
      collected from 1 wk after partial ligation when endothelial dysfunction occurs,
      but before atheroma develops, were analyzed by high-resolution mass spectrometry.
      A metabolome-wide association study showed that 128 metabolites were
      significantly altered in the ligated mice compared with the sham group. Of these,
      sphingomyelin (SM; m/z 703.5747), a common mammalian cell membrane sphingolipid,
      was most significantly increased in the ligated mice. Of the 128 discriminatory
      metabolites, 18 and 41 were positively and negatively correlated with SM,
      respectively. The amino acids methionine and phenylalanine were increased by d
      flow, while phosphatidylcholine and phosphatidylethanolamine were decreased by d
      flow, and these metabolites were correlated with SM. Other significantly affected
      metabolites included dietary and environmental agents. Pathway analysis showed
      that the metabolic changes of d-flow impacted broad functional networks. These
      results suggest that signaling from d-flow occurring in focal regions induces
      systemic metabolic changes associated with atherosclerosis. 

PMID- 25377481
TI  - Quantifying the effects of diuretics and beta-adrenoceptor blockers on glycaemic
      control in diabetes mellitus - a systematic review and meta-analysis.
AB  - AIMS: Although there are reports that beta-adrenoceptor antagonists (beta
      blockers) and diuretics can affect glycaemic control in people with diabetes
      mellitus, there is no clear information on how blood glucose concentrations may
      change and by how much. We report results from a systematic review to quantify
      the effects of these antihypertensive drugs on glycaemic control in adults with
      established diabetes. METHODS: We systematically reviewed the literature to
      identify randomized controlled trials in which glycaemic control was studied in
      adults with diabetes taking either beta-blockers or diuretics. We combined data
      on HbA1c and fasting blood glucose using fixed effects meta-analysis. RESULTS:
      From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies
      of diuretics to include in the meta-analysis. One study included both
      comparisons, totalling 21 included reports. Beta-blockers increased fasting blood
      glucose concentrations by 0.64 mmol l(-1) (95% CI 0.24, 1.03) and diuretics by
      0.77 mmol l(-1) (95% CI 0.14, 1.39) compared with placebo. Effect sizes were
      largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and
      thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c
      concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI -0.17,
      0.65) compared with placebo. There was no significant difference in the number of
      hypoglycaemic events between beta-blockers and placebo in three trials.
      CONCLUSIONS: Randomized trials suggest that thiazide diuretics and non-selective
      beta-blockers increase fasting blood glucose and HbA1c concentrations in patients
      with diabetes by moderate amounts. These data will inform prescribing and
      monitoring of beta-blockers and diuretics in patients with diabetes.

PMID- 25377483
TI  - Large surface relaxation in the organic semiconductor tetracene.
AB  - Organic crystals are likely to have a large degree of structural relaxation near
      their surfaces because of the weak inter-molecular interactions. The design of
      organic field-effect transistors requires a detailed knowledge of the surface
      relaxation as the carriers usually transfer within the first few molecular layers
      at the semiconductor surfaces, and their transport properties reflect the
      structural changes through the transfer integral. Here, we report the direct
      observation of the surface relaxation of an organic semiconductor, a tetracene
      single crystal, by means of X-ray crystal truncation rod scattering measurements.
      A significant degree of surface relaxation is observed, taking place only in the
      first monolayer at the semiconductor surface. First principles calculations show
      that the resultant transfer integrals are completely different between the bulk
      and surface of the semiconductor. 

PMID- 25377482
TI  - The effects of tympanomastoid paragangliomas on hearing and the audiological
      outcomes after surgery over a long-term follow-up.
AB  - The primary goals of surgery of tympanomastoid paragangliomas (TMPs) are tumor
      eradication and hearing preservation. Though the surgical management of TMPs has
      been dealt with widely in the literature, the effects of TMPs themselves on
      preoperative hearing and the audiological outcomes after surgery have not been
      analyzed in detail. This article comprehensively evaluates the preoperative
      hearing and the long-term hearing outcomes after surgery of TMPs. This study is
      based on a study population of 145 patients which is the largest reported in the
      literature. The surgical approaches for all patients with TMPs were formulated
      according to an algorithm developed by the authors. Complete tumor removal with
      excellent hearing results can be achieved by approaching the tumor classes by the
      right surgical technique. TMPs could possibly induce sensorineural hearing loss
      in higher frequencies, and future studies could be directed towards this.

PMID- 25377484
TI  - Phenol, 2,4-bis(1,1-dimethylethyl) of marine bacterial origin inhibits quorum
      sensing mediated biofilm formation in the uropathogen Serratia marcescens.
AB  - Intercellular communication in bacteria (quorum sensing, QS) is an important
      phenomenon in disease dissemination and pathogenesis, which controls biofilm
      formation also. This study reports the anti-QS and anti-biofilm efficacy of
      seaweed Gracilaria gracilis associated Vibrio alginolyticus G16 against Serratia
      marcescens. Purification and mass spectrometric analysis revealed the active
      principle as phenol, 2,4-bis(1,1-dimethylethyl) [PD]. PD affected the QS
      regulated virulence factor production in S. marcescens and resulted in a
      significant (p < 0.05) reduction in biofilm (85%), protease (41.9%), haemolysin
      (69.9%), lipase (84.3%), prodigiosin (84.5%) and extracellular polysaccharide
      (84.62%) secretion without hampering growth, as evidenced by XTT [2,3-bis (2
      methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. qPCR
      analysis confirmed the down-regulation of the fimA, fimC, flhD and bsmA genes
      involved in biofilm formation. Apart from biofilm inhibition and disruption, PD
      increased the susceptibility of S. marcescens to gentamicin when administered
      synergistically, which opens another avenue for combinatorial therapy where PD
      can be used to enhance the efficacy of conventional antibiotics. 

PMID- 25377485
TI  - Influence of substratum hydrophobicity on salivary pellicles: organization or
      composition?
AB  - Different physico-chemical properties (eg adsorption kinetics, thickness,
      viscoelasticity, and mechanical stability) of adsorbed salivary pellicles depend
      on different factors, including the properties (eg charge, roughness,
      wettability, and surface chemistry) of the substratum. Whether these differences
      in the physico-chemical properties are a result of differences in the composition
      or in the organization of the pellicles is not known. In this work, the influence
      of substratum wettability on the composition of the pellicle was studied. For
      this purpose, pellicles eluted from substrata of different but well-characterized
      wettabilities were examined by means of sodium dodecyl sulphate polyacrylamide
      gel electrophoresis (SDS-PAGE). The results showed that substratum hydrophobicity
      did not have a major impact on pellicle composition. In all substrata, the major
      pellicle components were found to be cystatins, amylases and large glycoproteins,
      presumably mucins. In turn, interpretation of previously reported data based on
      the present results suggests that variations in substratum wettability mostly
      affect the organization of the pellicle components. 

PMID- 25377486
TI  - Diatom community structure on in-service cruise ship hulls.
AB  - Diatoms are an important component of marine biofilms found on ship hulls.
      However, there are only a few published studies that describe the presence and
      abundance of diatoms on ships, and none that relate to modern ship hull coatings.
      This study investigated the diatom community structure on two in-service cruise
      ships with the same cruise cycles, one coated with an antifouling (AF) system
      (copper self-polishing copolymer) and the other coated with a silicone fouling
      release (FR) system. Biofilm samples were collected during dry docking from
      representative areas of the ship and these provided information on the horizontal
      and vertical zonation of the hull, and intact and damaged coating and niche
      areas. Diatoms from the genera Achnanthes, Amphora and Navicula were the most
      common, regardless of horizontal ship zonation and coating type. Other genera
      were abundant, but their presence was more dependent on the ship zonation and
      coating type. Samples collected from damaged areas of the hull coating had a
      similar community composition to undamaged areas, but with higher diatom
      abundance. Diatom fouling on the niche areas differed from that of the
      surrounding ship hull and paralleled previous studies that investigated
      differences in diatom community structure on static and dynamically exposed
      coatings; niche areas were similar to static immersion and the hull to dynamic
      immersion. Additionally, diatom richness was greater on the ship with the FR
      coating, including the identification of several new genera to the biofouling
      literature, viz. Lampriscus and Thalassiophysa. These results are the first to
      describe diatom community composition on in-service ship hulls coated with a FR
      system. This class of coatings appears to have a larger diatom community compared
      to copper-based AF systems, with new diatom genera that have the ability to stick
      to ship hulls and withstand hydrodynamic forces, thus creating the potential for
      new problematic species in the biofilm. 

PMID- 25377487
TI  - Reconstruction of biofilm images: combining local and global structural
      parameters.
AB  - Digitized images can be used for quantitative comparison of biofilms grown under
      different conditions. Using biofilm image reconstruction, it was previously found
      that biofilms with a completely different look can have nearly identical
      structural parameters and that the most commonly utilized global structural
      parameters were not sufficient to uniquely define these biofilms. Here,
      additional local and global parameters are introduced to show that these
      parameters considerably increase the reliability of the image reconstruction
      process. Assessment using human evaluators indicated that the correct
      identification rate of the reconstructed images increased from 50% to 72% with
      the introduction of the new parameters into the reconstruction procedure. An
      expanded set of parameters especially improved the identification of biofilm
      structures with internal orientational features and of structures in which colony
      sizes and spatial locations varied. Hence, the newly introduced structural
      parameter sets helped to better classify the biofilms by incorporating finer
      local structural details into the reconstruction process. 

PMID- 25377488
TI  - Nanofiber based triple layer hydro-philic/-phobic membrane--a solution for pore
      wetting in membrane distillation.
AB  - The innovative design and synthesis of nanofiber based hydro-philic/phobic
      membranes with a thin hydro-phobic nanofiber layer on the top and a thin
      hydrophilic nanofiber layer on the bottom of the conventional casted micro-porous
      layer which opens up a solution for membrane pore wetting and improves the pure
      water flux in membrane distillation. 

PMID- 25377489
TI  - Tricuspid regurgitation and implantable devices.
AB  - BACKGROUND: There are limited and conflicting data regarding the prevalence of
      tricuspid regurgitation (TR) after cardiac device implantation (implantable
      cardioverter defibrillator [ICD]; permanent pacemaker [PPM]). OBJECTIVE: The goal
      of this study was to assess the prevalence of TR after cardiac device
      implantation and determine its clinical significance. METHODS: A total of 1,596
      patients, who had cardiac devices implanted between 2005 and 2011 at the
      Cleveland Clinic and had at least one preimplantation echocardiogram and at least
      one postimplantation echocardiogram were included in this study. A total of 3,566
      postimplantation echocardiograms were available for the 1,596 patients (median
      follow-up 10 months). The primary end point was postimplantation TR and the
      secondary end point was all-cause mortality after implantation. We have used a
      cumulative logistic nonlinear mixed-effects model to assess the temporal trend of
      TR prevalence and a parametric multiphase hazard model to assess survival.
      RESULTS: Of the 1,596 patients (mean age: 60 +/- 10 years, 61% of patients were
      men), 985 (62%) had ICDs (including 334 patients with cardiac resynchronization
      therapy defibrillator) and 611 (38%) had PPMs. The prevalence of grade 3 or 4+ TR
      increased from 27% to 31% by 1 month and to 35% at 4 years. Accordingly,
      prevalence of grade 0/1+ TR decreased from 46% preimplantation to 37% at 1 month
      and to 32% at 4 years. Device type (ICD vs PPM) and the number of leads placed
      did not have an effect on postimplantation TR (P > 0.2). Right ventricular
      systolic pressure (RVSP) did not change over time (36 mm Hg baseline, 37.5 mm Hg
      by 3 months, and 37 mm Hg by 1 year). One-year and 5-year survival were 93% and
      73%, respectively. Postimplantation TR was an independent risk factor for late
      death (P < 0.05). CONCLUSION: Cardiac device implantation was associated with a
      small but significant increase in the prevalence of moderate and severe TR, both
      acutely and chronically after implantation. The increase in TR was similar with
      both ICD and PPM placement, which was not related to the number of leads
      implanted and not associated with a significant increase in RVSP.
      Postimplantation TR was associated with a higher risk of mortality.

PMID- 25377490
TI  - Neural stem cells in the immature, but not the mature, subventricular zone
      respond robustly to traumatic brain injury.
AB  - Pediatric traumatic brain injury is a significant problem that affects many
      children each year. Progress is being made in developing neuroprotective
      strategies to combat these injuries. However, investigators are a long way from
      therapies to fully preserve injured neurons and glia. To restore neurological
      function, regenerative strategies will be required. Given the importance of stem
      cells in repairing damaged tissues and the known persistence of neural precursors
      in the subventricular zone (SVZ), we evaluated regenerative responses of the SVZ
      to a focal brain lesion. As tissues repair more slowly with aging, injury
      responses of male Sprague Dawley rats at 6, 11, 17, and 60 days of age and
      C57Bl/6 mice at 14 days of age were compared. In the injured immature animals,
      cell proliferation in the dorsolateral SVZ more than doubled by 48 h. By
      contrast, the proliferative response was almost undetectable in the adult brain.
      Three approaches were used to assess the relative numbers of bona fide neural
      stem cells, as follows: the neurosphere assay (on rats injured at postnatal day
      11, P11), flow cytometry using a novel 4-marker panel (on mice injured at P14)
      and staining for stem/progenitor cell markers in the niche (on rats injured at
      P17). Precursors from the injured immature SVZ formed almost twice as many
      spheres as precursors from uninjured age-matched brains. Furthermore, spheres
      formed from the injured brain were larger, indicating that the neural precursors
      that formed these spheres divided more rapidly. Flow cytometry revealed a 2-fold
      increase in the percentage of stem cells, a 4-fold increase in multipotential
      progenitor-3 cells and a 2.5-fold increase in glial-restricted progenitor
      2/multipotential-3 cells. Analogously, there was a 2-fold increase in the mitotic
      index of nestin+/Mash1- immunoreactive cells within the immediately subependymal
      region. As the early postnatal SVZ is predominantly generating glial cells, an
      expansion of precursors might not necessarily lead to the production of many new
      neurons. On the contrary, many BrdU+/doublecortin+ cells were observed streaming
      out of the SVZ into the neocortex 2 weeks after injuries to P11 rats. However,
      very few new mature neurons were seen adjacent to the lesion 28 days after
      injury. Altogether, these data indicate that immature SVZ cells mount a more
      robust proliferative response to a focal brain injury than adult cells, which
      includes an expansion of stem cells, primitive progenitors and neuroblasts.
      Nonetheless, this regenerative response does not result in significant neuronal
      replacement, indicating that new strategies need to be implemented to retain the
      regenerated neurons and glia that are being produced.

PMID- 25377491
TI  - Rapid detection of dermatophytes and Candida albicans in onychomycosis specimens
      by an oligonucleotide array.
AB  - BACKGROUND: Onychomycosis is a fungal infection of nails, leading to the gradual
      destruction of the nail plate. Treatment of onychomycosis may need long-time oral
      antifungal therapy that can have potential side effects, thus accurate diagnosis
      of the disease before treatment is important. Culture for diagnosis of
      onychomycosis is time-consuming and has high false-negative rates. To expedite
      the diagnosis, an oligonucleotide array, based on hybridization between
      immobilized oligonucleotide probes and PCR products, for direct detection of
      dermatophytes and Candida albicans in clinical specimens was evaluated. METHODS:
      Species-specific oligonucleotide probes designed from the internal transcribed
      spacer (ITS) regions of the rRNA gene were immobilized on a nylon membrane. The
      assay procedures consisted of PCR amplification of the ITS using universal
      primers, followed by hybridization of the digoxigenin-labeled amplicons to probes
      on the array. Thirty two nail samples (29 patients) were analyzed by the array,
      and the results were compared with those obtained by culture. Array-positive but
      culture-negative samples were confirmed by cloning and re-sequencing of the
      amplified ITS and by reviewing patient's clinical data. The total recovery of
      culture and confirmed array-positive but culture-negative results was considered
      100% and was used for performance evaluation of both methods. RESULTS: Concordant
      results were obtained in 21 samples (10 positives and 11 negatives) by both
      methods. Eleven samples were array-positive but culture-negative; among them, 9
      samples were considered true positives after discrepant analysis. Comparing with
      culture, the array had significantly higher sensitivity [100% (95% CI 82.2% 
      100%) vs 52.6% (28.9% -75.5%), p <0.001] and negative predictive value [100%
      (71.3% -100%) vs 59.1% (36.4% -79.3%), p <0.05), while no significant differences
      were observed in specificity (84.6% vs 100%, p =0.48) and positive predictive
      value (90.5% vs 100%, p =1.0). The whole procedures of the array were about 24 h,
      whilst results from culture take 1 to 3 weeks. CONCLUSIONS: The array offers an
      accurate and rapid alternative to culture. Rapid diagnosis can expedite
      appropriate antifungal treatment of onychomycosis. However, the single site
      nature of this study conducted at a referral hospital invites caution.

PMID- 25377492
TI  - Krogh-cylinder and infinite-domain models for washout of an inert diffusible
      solute from tissue.
AB  - OBJECTIVE: Models based on the Krogh-cylinder concept are developed to analyze
      the washout from tissue by blood flow of an inert diffusible solute that
      permeates blood vessel walls. During the late phase of washout, the outflowing
      solute concentration decays exponentially with time. This washout decay rate is
      predicted for a range of conditions. METHODS: A single capillary is assumed to
      lie on the axis of a cylindrical tissue region. In the classic "Krogh-cylinder"
      approach, a no-flux boundary condition is applied on the outside of the cylinder.
      An alternative "infinite-domain" approach is proposed that allows for solute
      exchange across the boundary, but with zero net exchange. Both models are
      analyzed, using finite-element and analytical methods. RESULTS: The washout decay
      rate depends on blood flow rate, tissue diffusivity and vessel permeability of
      solute, and assumed boundary conditions. At low blood flow rates, the washout
      rate can exceed the value for a single well-mixed compartment. The infinite
      domain approach predicts slower washout decay rates than the Krogh-cylinder
      approach. CONCLUSIONS: The infinite-domain approach overcomes a significant
      limitation of the Krogh-cylinder approach, while retaining its simplicity. It
      provides a basis for developing methods to deduce transport properties of inert
      solutes from observations of washout decay rates.

PMID- 25377493
TI  - Three-dimensional Electrical Property Mapping with Nanometer Resolution.
AB  - The conductivity behavior of MWCNT networks within the volume of polymer
      nanocomposite samples is analyzed with nanometer resolution in all three
      dimensions. It is demonstrated that close to but above the percolation threshold
      for electrical conduction most of the MWCNTs do not contribute to the conductive
      network within the nanocomposite. 

PMID- 25377494
TI  - Difference in correspondence between visual field defect and inner macular layer
      thickness measured using three types of spectral-domain OCT instruments.
AB  - PURPOSE: To compare the relationship between visual field sensitivity (VFS) and
      macular parameters measured using three spectral-domain optical coherence
      tomography (SD-OCT) instruments and to determine a base level (=floor effect) for
      macular parameters. METHODS: We imaged 127 glaucomatous eyes (1 eye per subject)
      using three different OCT instruments, i.e., the Cirrus, RTVue and 3D OCT
      devices; 76 normal eyes were evaluated as controls using the same instruments.
      The thicknesses of the macular retinal nerve fiber layer (mRNFL), ganglion cell
      layer+inner plexiform layer (GCL/IPL), and mRNFL+GCL/IPL (GCC) were analyzed. The
      VFS of the area analyzed by OCT was expressed in decibels and the 1/Lambert
      scale. For each parameter, the structure-function relationship and the base level
      were evaluated by regression analysis. The strength of the correlations between
      the instruments was compared by the bootstrapping method. RESULTS: All of the
      macular parameters evaluated exhibited statistically significant correlations
      with VFS. The average GCC measured by all three SD-OCT instruments and the
      average mRNFL thickness measured by the Cirrus and 3D OCT instruments had similar
      correlations with VFS. The average GCL/IPL thickness measured by the Cirrus OCT
      instrument was better correlated with VFS that was measured by the 3D OCT
      instrument (p = 0.031). The base level GCC thickness measured by all three
      instruments was approximately 65% of that of normal eyes. The base level mRNFL
      thickness measured with the Cirrus and OCT instruments was 52 and 48%,
      respectively, of that of normal eyes. The base level GCL/IPL thickness measured
      with the Cirrus and 3D instruments was 71 and 75%, respectively, of that of
      normal eyes. CONCLUSIONS: The three SD-OCT instruments evaluated showed similar
      structure-function relationships in terms of GCC and mRNFL measurements. The base
      levels of the macular parameters determined by the three instruments differed,
      due, at least partly, to the scanning area defined by each instrument.

PMID- 25377495
TI  - Orbital blowout fracture location in Japanese and Chinese patients.
AB  - PURPOSE: To characterize the location of orbital blowout fractures in Asian
      individuals. METHODS: This was a retrospective review of 470 consecutive Asian
      patients with orbital blowout fractures who presented to four tertiary care
      hospitals in Japan and China. Computed tomography (CT) characterized the location
      and severity of fractures involving the medial wall, the orbital floor, and/or
      the maxilloethmoidal strut. RESULTS: A total of 475 orbital blowout fractures
      were identified. More than one fracture location was involved in 19% of all
      cases. The medial orbital wall was the most commonly involved location,
      presenting in 29 cases (61%), of which 204 (43%) were isolated medial blowout
      fractures. The orbital floor was the second most common location involved,
      present in 226 cases (48%) with 150 isolated orbital floor fractures (32%), while
      the maxilloethmoidal strut was involved in 45 cases (9%) with 30 of those being
      isolated strut fractures (6%). The majority of fractures (62%) were classified as
      moderately severe, whilst 14% were mild, and 24% were severe. Associated nasal
      fractures were present in 16% of the cases. CONCLUSIONS: Orbital blowout
      fractures in Japanese and Chinese individuals occur most commonly in the medial
      wall. This is in contrast to previous reports on white individuals, who tend to
      sustain fractures involving the orbital floor rather than the medial wall.

PMID- 25377497
TI  - Estrogens, the be-all and end-all of male hypogonadal bone loss?

PMID- 25377496
TI  - Preservation of volumetric bone density and geometry in trans women during cross
      sex hormonal therapy: a prospective observational study.
AB  - Although trans women before the start of hormonal therapy have a less bone and
      muscle mass compared with control men, their bone mass and geometry are preserved
      during the first 2 years of hormonal therapy, despite of substantial muscle loss,
      illustrating the major role of estrogen in the male skeleton. PURPOSE: The aim of
      this study is to examine the evolution of areal and volumetric bone density,
      geometry, and turnover in trans women undergoing sex steroid changes, during the
      first 2 years of hormonal therapy. METHODS: In a prospective observational study,
      we examined 49 trans women (male-to-female) before and after 1 and 2 years of
      cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men
      measuring grip strength (hand dynamometer), areal bone mineral density (aBMD),
      and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone
      geometry and volumetric bone mineral density, regional fat, and muscle area at
      the forearm and calf using peripheral quantitative computed tomography.
      Standardized treatment regimens were used with oral estradiol valerate, 4 mg
      daily (or transdermal 17-beta estradiol 100 MUg/24 h for patients >45 years old),
      both combined with oral cyproterone acetate 50 mg daily. RESULTS: Prior to CSH,
      trans women had lower aBMD at all measured sites (all p < 0.001), smaller
      cortical bone size (all p < 0.05), and lower muscle mass and strength and lean
      body mass (all p < 0.05) compared with control men. During CSH, muscle mass and
      strength decreased and all measures of fat mass increased (all p < 0.001). The
      aBMD increased at the femoral neck, radius, lumbar spine, and total body;
      cortical and trabecular bone remained stable and bone turnover markers decreased
      (all p < 0.05). CONCLUSIONS: Although trans women, before CSH, have a lower aBMD
      and cortical bone size compared with control men, their skeletal status is well
      preserved during CSH treatment, despite of substantial muscle loss.

PMID- 25377498
TI  - Trends in fall-related hospitalisations in older people living in aged care
      facilities.
AB  - The aim is to describe the trends in fall-related hospitalisations for older
      people living in aged care facilities. Over the 9-year period investigated, there
      were dramatic increases in fall-related hospitalisations. This worrying trend
      highlights that we may not be addressing falls in aged care facilities
      sufficiently. INTRODUCTION: The purposes of this study are to describe the trends
      in fall-related hospitalisations in older people living in aged care facilities
      and to compare these trends across different demographic groups and injury types.
      METHODS: This study was conducted in Australia's second most populous state,
      Victoria. Aged care facilities in Australia provide high- and low-level nursing
      care for people who can no longer live independently. Included in this study were
      hospital admitted episodes of care which met the following criteria: age 65+
      years at admission, an admission source indicating a transfer from an aged care
      facility, an external cause indicating a fall, a care type of 'acute', a
      Victorian postcode of residence, and an admission date between July 1, 2003 and
      June 30, 2012 (inclusive). Rate denominator data were Victorian aged care bed
      years. RESULTS: Over the last 9 years, 7098 episodes of care met the inclusion
      criteria. The age-standardised rate of hospitalisation increased by 11% (95%
      confidence interval [CI] 9%, 12%) per year. Serious injury increased at a slower
      pace than less serious injury. The slowest rate increase was for hip fracture
      (incidence rate ratio: 1.03 (95% CI 1.00, 1.06), the most common fracture type.
      CONCLUSIONS: Rates of fall-related hospitalisations in older people living in
      aged care facilities increased at a dramatic pace in the period studied. The
      relative slower increase in hip fracture may point towards changing referral
      practices, possible success in osteoporosis management, body mass index increases
      in older people living in aged care facilities or a combination of these factors.

PMID- 25377499
TI  - Frontotemporal dementia with parkinsonism linked to chromosome 17 with the MAPT
      R406W mutation presenting with a broad distribution of abundant senile plaques.
AB  - We report the autopsy results of a patient with familial dementia who was
      diagnosed as having frontotemporal dementia with parkinsonism linked to
      chromosome 17 (FTDP-17) with an R406W mutation in the microtubule-associated
      protein tau (MAPT) gene. This patient showed Alzheimer's disease (AD)-like
      clinical manifestations from the age of 59, with reduced beta-amyloid1-42
      (Abeta42 ) and elevated total and phosphorylated tau levels in the cerebrospinal
      fluid. He did not present with any apparent parkinsonism throughout the disease
      course. His autopsy at age 73 showed atrophy and neurodegeneration in many brain
      regions, particularly in the antero-medial temporal cortex and hippocampus,
      followed by the frontal lobes, with abundant neurofibrillary tangles. In
      addition, a diffuse distribution of Abeta-positive senile plaques, including many
      neuritic plaques, was observed and classified as stage C according to the
      Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.
      These results suggest that analyzing of the MAPT gene is essential for diagnosing
      familial dementia, even if amyloid markers such as Abeta42 in the cerebrospinal
      fluid and amyloid imaging are positive, or if neuropathological findings indicate
      a diagnosis of AD.

PMID- 25377500
TI  - Evaluating p97 inhibitor analogues for their domain selectivity and potency
      against the p97-p47 complex.
AB  - We previously found that p97 ATPase inhibitors 2-(2-amino-1H-benzo[d]imidazol-1
      yl)-N-benzyl-8-methoxyquinazolin-4-amine (ML240) and 2-(2H-benzo[b][1,4]oxazin
      4(3H)-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine (ML241) specifically
      target the D2 domain of wild-type p97. In addition, one of the major p97
      cofactors, p47, decreases their potencies by ~50-fold. In contrast, N(2) ,N(4) 
      dibenzylquinazoline-2,4-diamine (DBeQ) targets both the D1 and D2 domains and
      shows only a four- to sixfold decrease in potency against the p97-p47 complex. To
      elucidate structure-activity relationships for the inhibitors, we screened 200
      p97 inhibitor analogues for their ability to inhibit the ATPase activity of
      either or both of the D1 or D2 domains, as well for their effects on p47 potency.
      The selectivity of 29 of these compounds was further examined by eight-dose
      titrations. Four compounds showed modest selectivity for inhibiting the ATPase
      activity of D1. Eleven compounds inhibited D2 with greater potencies, and four
      showed similar potencies against D1 and D2. p47 decreased the potencies of the
      majority of the compounds and increased the potencies of five compounds. These
      results highlight the possibility of developing domain-selective and complex
      specific p97 inhibitors in order to further elucidate the physiological roles of
      p97 and its cofactors. 

PMID- 25377501
TI  - Arthroscopically Assisted Treatment of Navicular Osteochondral Defect Using
      Flowable Collagen, Iliac Crest Bone Marrow Aspirate and Fibrin Glue: A Case
      Report.
AB  - A 32-year-old male recreational athlete presented with activity-related chronic
      dorsal midfoot pain. Conservative treatment, including a prolonged period of
      immobilization, physical therapy, nonsteroidal anti-inflammatory drugs, and use
      of a bone stimulator, failed to resolve his symptoms. Computed tomography and
      magnetic resonance imaging demonstrated a cystic appearing focus within the
      navicular in conjunction with a osteochondral lesion within the proximal
      articular surface of the navicular. This case report presents an arthroscopically
      assisted treatment of a navicular osteochondral lesion using curettage and
      backfilling with fibrin glue, flowable collagen, and autogenous bone grafting.
      LEVELS OF EVIDENCE: Therapeutic, Level IV.

PMID- 25377502
TI  - Peroneal Tendon Impingement due to Bulky Osteochondroma: A Case Report.
AB  - Osteochondromas are the most common benign bone tumors. Although many are
      asymptomatic, they can produce a mass effect impinging against soft tissues or
      interfering with joint function. The authors present a case report and review of
      literature of an ankle osteochondroma successfully treated by excision. LEVELS OF
      EVIDENCE: Therapeutic, Level IV: Case Report.

PMID- 25377504
TI  - Single fetal demise in monochorionic pregnancies: incidence and patterns of
      cerebral injury.
AB  - OBJECTIVE: To evaluate the incidence, type and severity of cerebral injury in the
      surviving monochorionic (MC) cotwin after single fetal demise in twin
      pregnancies. METHODS: All MC pregnancies with single fetal demise that were
      evaluated at the Leiden University Medical Center between 2002 and 2013 were
      included. Perinatal characteristics, neonatal outcome and the presence of
      cerebral injury, observed on neuroimaging, were recorded for all cotwin
      survivors. RESULTS: A total of 49 MC pregnancies with single fetal demise,
      including one MC triplet, were included in the study (n = 50 cotwins). Median
      gestational age at occurrence of single fetal demise was 25 weeks and median
      interval between single fetal demise and live birth was 61 days, with a median
      gestational age at birth of 36 weeks. Severe cerebral injury was diagnosed in 13
      (26%) of the 50 cotwins and was detected antenatally in 4/50 (8%) and postnatally
      in 9/50 (18%) cases. Cerebral injury was mostly due to hypoxic-ischemic injury
      resulting in cystic periventricular leukomalacia, middle cerebral artery
      infarction or injury to basal ganglia, thalamus and/or cortex. Risk factors
      associated with severe cerebral injury were advanced gestational age at the
      occurrence of single fetal demise (odds ratio (OR), 1.14 (95% CI, 1.01-1.29) for
      each week of gestation; P = 0.03), twin-twin transfusion syndrome developing
      prior to single fetal demise (OR, 5.0 (95% CI, 1.30-19.13); P = 0.02) and a lower
      gestational age at birth (OR, 0.83 (95% CI, 0.69-0.99) for each week of
      gestation; P = 0.04). CONCLUSIONS: Single fetal demise in MC pregnancies is
      associated with severe cerebral injury occurring in 1 in 4 surviving cotwins.
      Routine antenatal and postnatal neuroimaging, followed by standardized long-term
      follow-up, is mandatory.

PMID- 25377505
TI  - Intra-articular treatment with triamcinolone compared with triamcinolone with
      hyaluronate: A randomised open-label multicentre clinical trial in 80 lame
      horses.
AB  - REASONS FOR PERFORMING STUDY: Intra-articular (IA) injection of corticosteroids
      with or without hyaluronate (HA) has been used for decades in equine practice for
      treatment of noninfectious synovitis and osteoarthritis. However, to date, no
      large-scale randomised equine field trials have been reported that address the
      supposed superior clinical efficacy of the combination of corticosteroid + HA
      compared with IA injection of corticosteroid alone. OBJECTIVES: To compare the
      clinical efficacy of IA triamcinolone acetonide (TA, 12 mg) compared with IA TA
      (12 mg) + high molecular weight HA (20 mg) in horses with clinical joint disease.
      STUDY DESIGN: Prospective, randomised, parallel, open label, multicentre clinical
      trial. METHODS: Eighty client-owned horses from 13 clinics were included.
      Lameness and effusion scores were assessed at baseline and 3 weeks after IA
      treatment. A standardised telephone questionnaire was completed between the owner
      and consulting veterinarian at 3 months. The primary outcome parameter was
      clinical success rate, defined as >=2 grades lameness reduction (on a 0-5 scale)
      at 3 weeks. Chi-square statistics and binary logistic regression were used to
      analyse data on an intention-to-treat basis for the 3 week outcome. RESULTS: The
      success rate of IA TA 3 weeks after treatment was 87.8%, while that of TA+HA was
      64.1% (P = 0.01). Age >13 years was associated with a reduced success rate for
      the combination treatment (P = 0.004) at 3 weeks. At 3 months, half the horses in
      each group had returned to their previous level of performance. CONCLUSIONS: The
      combination of TA with HA was associated with a lower short-term clinical success
      rate and a similar medium-term outcome compared with IA TA, with only half of the
      horses performing at their previous level of exercise after 3 months regardless
      of treatment group allocation.

PMID- 25377506
TI  - Risk factors and impact of retained fetal membranes on performance of dairy
      bovines reared under subtropical conditions.
AB  - The risk factors and impact of retained fetal membranes (RFM) on productive and
      reproductive performance of crossbred cattle, Zebu cattle, and Murrah buffalos
      were evaluated using data spread over 12 years. Multivariable logistic regression
      model was used to identify risk factors and to quantify their odds ratio (OR).
      Overall incidence of RFM in crossbred cattle, Zebu cattle, and Murrah buffalos
      were 26, 16, and 13 %, respectively; and significant risk factors for RFM in
      crossbred cattle were abortion (OR = 3.9), dead calf (OR = 4.1), dystocia (OR =
      4.3), pluriparity (OR = 1.5), and shorter gestation length (OR = 4.3). In Zebu
      cattle, abortion (OR = 4.0), dead calf (OR = 3.7), dystocia (OR = 3.9), lower
      birth weight of calf (OR = 1.6), and shorter gestation length (OR = 6.4) were
      significant risk factors for RFM. In Murrah buffalos, abortion (OR = 19.2), dead
      calf (OR = 4.4), dystocia (OR = 4.7), pluriparity (OR = 1.7), shorter gestation
      length (OR = 12.7), and calving during summer season (OR = 1.8) were the risk
      factors for RFM. Although the occurrence of RFM did not affect fertility
      parameters, a significant (P < 0.05) decrease in 305-day milk yield and total
      milk yield was observed in RFM-affected crossbred cattle. Taken together, it may
      be concluded that increased parity, abnormal calving, and short gestation length
      were the main risk factors for RFM in dairy bovine. 

PMID- 25377503
TI  - Medical follow-up for workers exposed to bladder carcinogens: the French evidence
      based and pragmatic statement.
AB  - BACKGROUND: The aim of this work was to establish recommendations for the medical
      follow-up of workers currently or previously exposed to carcinogenic substances
      for the bladder. METHODS: A critical synthesis of the literature was conducted.
      Sectors of activity where workers are or were exposed to carcinogenic substances
      for the bladder were listed and classified according to the level of bladder
      cancer risk. Performances of techniques available for the targeted screening of
      bladder cancer were analysed, including a simulation of results among high-risk
      populations in France. RESULTS: The risk level for the professional group and the
      latency period between the start of exposure and the natural history of the
      disease were selected to define a targeted screening protocol. The NMP22BC test,
      exclusive haematuria testing, and combinations of urine cytology with,
      respectively, the NMP22BC test and haematuria test, generated an extremely high
      proportion of false positive results. CONCLUSION: Urine cytology is the test that
      offers the best specificity. Although poor for all bladder cancer stages and
      grades combined, its sensitivity is better for high grades, which require early
      diagnosis since late-stage cancers are of very poor prognosis. These results
      suggest that urine cytology is currently the only technique suitable for proposal
      within the context of a first line targeted screening strategy for occupational
      bladder cancer. An algorithm summarising the recommended medical follow-up for
      workers currently or previously exposed to carcinogenic substances for the
      bladder is proposed, based on the level of risk of bladder cancer.

PMID- 25377507
TI  - Phase 2, randomized, open-label study of ramucirumab in combination with first
      line pemetrexed and platinum chemotherapy in patients with nonsquamous,
      advanced/metastatic non-small cell lung cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF)-mediated angiogenesis plays
      an important role in non-small cell lung cancer (NSCLC). Ramucirumab is a human
      immunoglobulin G1 monoclonal antibody that inhibits VEGF receptor 2. This phase 2
      study investigated ramucirumab in combination with first-line pemetrexed and
      platinum chemotherapy in advanced/metastatic NSCLC. METHODS: Eligible stage IV
      nonsquamous NSCLC patients with no prior chemotherapy for metastatic disease were
      randomized 1:1 to pemetrexed and carboplatin (or cisplatin) or ramucirumab (10
      mg/kg) plus pemetrexed and carboplatin (or cisplatin) once every 3 weeks.
      Treatment was given for 4 to 6 cycles, and this was followed by a maintenance
      phase with pemetrexed or ramucirumab and pemetrexed. The primary endpoint was
      progression-free survival (PFS) with a sample size of sufficient power to detect
      an increase from 7 to 10.4 months. RESULTS: From October 2010 to October 2011,
      140 patients were randomized (pemetrexed-platinum arm, 71; ramucirumab-pemetrexed
      platinum arm, 69), and most baseline characteristics were similar for the 2
      treatment arms. The median PFS was 5.6 months for the pemetrexed-platinum arm and
      7.2 months for the ramucirumab-pemetrexed-platinum arm (hazard ratio, 0.75; P =
      .132). The objective response rates were 38.0% and 49.3% for the pemetrexed
      platinum and ramucirumab-pemetrexed-platinum arms, respectively (P = .180). The
      disease control rate was 70.4% for the pemetrexed-platinum arm and 85.5% for the
      ramucirumab-pemetrexed-platinum arm (P = .032). The grade 3 or higher adverse
      events occurring in 10% or more of patients were thrombocytopenia, neutropenia,
      fatigue, anemia, nausea, back pain, and hypertension. CONCLUSIONS: The primary
      endpoint of significant prolongation of PFS was not met; however, ramucirumab
      showed evidence of clinical activity in combination with pemetrexed and platinum
      in nonsquamous NSCLC patients. The addition of ramucirumab to pemetrexed and
      platinum did not result in new or unexpected safety findings.

PMID- 25377508
TI  - Cueing others' memories.
AB  - Many situations require us to generate external cues to support later retrieval
      from memory. For instance, we create file names in order to cue our memory to a
      file's contents, and instructors create lecture slides to remember what points to
      make during classes. We even generate cues for others when we remind friends of
      shared experiences or send colleagues a computer file that is named in such a way
      so as to remind them of its contents. Here we explore how and how well learners
      tailor retrieval cues for different intended recipients. Across three
      experiments, subjects generated verbal cues for a list of target words for
      themselves or for others. Learners generated cues for others by increasing the
      normative cue-to-target associative strength but also by increasing the number of
      other words their cues point to, relative to cues that they generated for
      themselves. This strategy was effective: such cues supported higher levels of
      recall for others than cues generated for oneself. Generating cues for others
      also required more time than generating cues for oneself. Learners responded to
      the differential demands of cue generation for others by effortfully excluding
      personal, episodic knowledge and including knowledge that they estimate to be
      broadly shared. 

PMID- 25377509
TI  - Verbal and visual-spatial working memory and mathematical ability in different
      domains throughout primary school.
AB  - The relative importance of visual-spatial and verbal working memory for
      mathematics performance and learning seems to vary with age, the novelty of the
      material, and the specific math domain that is investigated. In this study, the
      relations between verbal and visual-spatial working memory and performance in
      four math domains (i.e., addition, subtraction, multiplication, and division) at
      different ages during primary school are investigated. Children (N = 4337) from
      grades 2 through 6 participated. Visual-spatial and verbal working memory were
      assessed using online computerized tasks. Math performance was assessed at the
      start, middle, and end of the school year using a speeded arithmetic test.
      Multilevel Multigroup Latent Growth Modeling was used to model individual
      differences in level and growth in math performance, and examine the predictive
      value of working memory per grade, while controlling for effects of classroom
      membership. The results showed that as grade level progressed, the predictive
      value of visual-spatial working memory for individual differences in level of
      mathematics performance waned, while the predictive value of verbal working
      memory increased. Working memory did not predict individual differences between
      children in their rate of performance growth throughout the school year. These
      findings are discussed in relation to three, not mutually exclusive, explanations
      for such age-related findings. 

PMID- 25377510
TI  - How does enactment affect the ability to follow instructions in working memory?
AB  - Recent studies examining working memory for sequences of instructions have
      demonstrated a performance advantage when the instructions are physically enacted
      rather than verbally recalled. However, little is known about the source of this
      effect, or how instructions are stored in working memory more generally. In
      particular, no previous studies have compared the impacts of enactment on
      encoding versus recall in working memory. We conducted an experiment to examine
      the impacts of enactment on both the encoding and recall phases of a task
      measuring memory for sequences of simple action-object pairs (e.g., touch the
      circle, spin the cross, flip the square, . . .) in young adult participants. An
      advantage for enacted over verbal recall was observed, in line with recent
      evidence. In addition, the enactment of actions during the encoding phase on each
      trial significantly facilitated subsequent performance; this effect was
      particularly apparent for verbal repetition rather than enacted recall. These
      findings are interpreted as reflecting a beneficial role for spatial-motoric
      coding in working memory that can be engaged through either action planning or
      physical performance. 

PMID- 25377511
TI  - TGF-beta1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human
      articular chondrocytes and marrow-derived stromal cells.
AB  - Replacement of degenerated cartilage with cell-based cartilage products may offer
      a long-term solution to halt arthritis' degenerative progression. Chondrocytes
      are frequently used in cell-based FDA-approved cartilage products; yet human
      marrow-derived stromal cells (hMSCs) show significant translational potential,
      reducing donor site morbidity and maintaining their undifferentiated phenotype
      with expansion. This study sought to investigate the effects of transforming
      growth factor beta1 (TGF-beta1), growth/differentiation factor 5 (GDF-5), and
      bone morphogenetic protein 2 (BMP-2) during postexpansion chondrogenesis in human
      articular chondrocytes (hACs) and to compare chondrogenesis in passaged hACs with
      that of passaged hMSCs. Through serial expansion, chondrocytes dedifferentiated,
      decreasing expression of chondrogenic genes while increasing expression of
      fibroblastic genes. However, following expansion, 10 ng/mL TGF-beta1, 100 ng/mL
      GDF-5, or 100 ng/mL BMP-2 supplementation during three-dimensional aggregate
      culture each upregulated one or more markers of chondrogenic gene expression in
      both hACs and hMSCs. Additionally, in both cell types, the combination of TGF
      beta1, GDF-5, and BMP-2 induced the greatest upregulation of chondrogenic genes,
      that is, Col2A1, Col2A1/Col1A1 ratio, SOX9, and ACAN, and synthesis of cartilage
      specific matrix, that is, glycosaminoglycans (GAGs) and ratio of collagen II/I.
      Finally, TGF-beta1, GDF-5, and BMP-2 stimulation yielded mechanically robust
      cartilage rich in collagen II and GAGs in both cell types, following 4 weeks
      maturation. This study illustrates notable success in using the self-assembling
      method to generate robust, scaffold-free neocartilage constructs using expanded
      hACs and hMSCs.

PMID- 25377512
TI  - Remote control of signaling pathways using magnetic nanoparticles.
AB  - Our ability to quantitatively control the spatiotemporal properties of cellular
      information processing is key for understanding biological systems at both
      mechanistic and systemic level. In this context, magnetic field offers a relevant
      strategy of control over cellular processes that broaden the toolbox currently
      available in cell biology. Among the increasing number of methods, we will focus
      on recent advances based on magnetic nanoparticles conjugated to proteins to
      trigger specific signaling pathways and cellular processes. Extracellular or
      intracellular manipulations of nanoparticles permit magnetic control of ion
      channels and membrane receptor activation, protein positioning within cells and
      cytoskeleton spatial engineering. These approaches provide powerful strategies to
      examine the organization principles of living cells.

PMID- 25377513
TI  - Commentary: Genetic testing in epilepsy: what do patients and families want to
      know?

PMID- 25377514
TI  - Simultaneous transcriptome analysis of Colletotrichum gloeosporioides and tomato
      fruit pathosystem reveals novel fungal pathogenicity and fruit defense
      strategies.
AB  - The fungus Colletotrichum gloeosporioides breaches the fruit cuticle but remains
      quiescent until fruit ripening signals a switch to necrotrophy, culminating in
      devastating anthracnose disease. There is a need to understand the distinct
      fungal arms strategy and the simultaneous fruit response. Transcriptome analysis
      of fungal-fruit interactions was carried out concurrently in the appressoria,
      quiescent and necrotrophic stages. Conidia germinating on unripe fruit cuticle
      showed stage-specific transcription that was accompanied by massive fruit defense
      responses. The subsequent quiescent stage showed the development of dendritic
      like structures and swollen hyphae within the fruit epidermis. The quiescent
      fungal transcriptome was characterized by activation of chromatin remodeling
      genes and unsuspected environmental alkalization. Fruit response was portrayed by
      continued highly integrated massive up-regulation of defense genes. During
      cuticle infection of green or ripe fruit, fungi recapitulate the same
      developmental stages but with differing quiescent time spans. The necrotrophic
      stage showed a dramatic shift in fungal metabolism and up-regulation of
      pathogenicity factors. Fruit response to necrotrophy showed activation of the
      salicylic acid pathway, climaxing in cell death. Transcriptome analysis of C.
      gloeosporioides infection of fruit reveals its distinct stage-specific lifestyle
      and the concurrent changing fruit response, deepening our perception of the
      unfolding fungal-fruit arms and defenses race. 

PMID- 25377515
TI  - Adult tonsillectomy: anatomical differences affect postoperative transient
      hypernasality.
AB  - OBJECTIVE: Our purpose was to determine how anatomical conditions of the throat
      influence the degree and duration of posttonsillectomy transient hypernasality.
      PATIENTS AND METHODS: A total of 82 tonsillectomies were performed. The
      participants were divided into groups: 1 - small tonsils, high soft palate
      position; 4 - large tonsils, low soft palate position, and 2 and 3 - intermediate
      tonsil dimensions and soft palate positions. Variables studied included the
      diameter of vapor (DV) on the mirror positioned under the patient's nose while
      articulating nasal sentences before and after surgery, the distance from the
      uvular tip to the posterior pharyngeal wall, healing grading as well as the
      degree and duration of hypernasality. RESULTS: The mean hypernasality after
      tonsillectomy was greatest in group 4 and lowest in group 2. Before
      tonsillectomy, the mean DV was largest in group 2 and smallest in group 4. After
      tonsillectomy, the mean DV was largest in group 4 and smallest in group 3.
      Overall, the mean DV was significantly greater after tonsillectomy compared to
      the value before surgery. CONCLUSION: The degree of hypernasality after
      tonsillectomy depends on the soft palate position in relation to the tongue base
      and the size of the tonsils. Hypernasality is greatest in patients with large
      tonsils and a low soft palate position in relation to the tongue base.

PMID- 25377517
TI  - [The Influence of Laparoscopic Fundoplication on Reflux-Associated Cough].
AB  - Introduction: The gastrooesophageal reflux disease (GERD) is a possible cause of
      chronic cough. The laparoscopic fundoplication is well established in the
      treatment of GERD. In a retrospective study, the effectivity of this operation on
      the GERD associated cough was examined and possible preoperative predictive
      factors concerning the post-surgical therapy effect were characterized. Patients
      and Methods: 85 patients after laparoscopic fundoplication due to GERD treated
      with proton pump inhibitors without (RS-H: n = 31) or with associated cough
      (RS+H: n = 54) were evaluated in a three-month follow-up by data analysis
      regarding an indication point score from typical symptoms as well as findings
      (gastroscopy, histology, 24-hour oesophagus pH-metry). Results: For the leading
      symptoms of heartburn and regurgitation a complete freedom from complaints was
      reached with 98.8 % of all patients postal-surgically. In the group RS+H 70.4 %
      of the patients were free of cough after 3 months, other 22.2 % with significant
      improvement and 7.4 % with unchanged irritant cough. Higher values of the typical
      reflux symptoms and a therapy resistance to proton pump inhibitors (PPI) were
      clearly seen in the RS-H patients. The RS+H patients showed less reflux
      complaints with lower PPI resistance, frequent allergies as well as significantly
      more often an acid or bitter taste and hoarseness. After further subdivision of
      the RS+H patients into the subgroups RS>H (mainly reflux, n = 31) and H>RS
      (mainly cough), the lowest values for heartburn, regurgitation and PPI resistance
      were found in subgroup H>RS. Diagnostics did not show any significiant
      differences between the groups although a trend could be seen towards fewer
      duodenogastric bile reflux, larger hiatus hernias and higher DeMeester scores in
      RS+H and H>RS. Also smokers, non-allergic asthmatics and polyallergic sufferers
      with cough profited from the intervention. Conclusion: Patients with reflux
      associated respiratory symptoms present an own entity with good PPI therapy
      response to heartburn, but not to cough. They should be considered more often for
      surgery. Since the cough symptoms in more than two-thirds of appropriately
      selected patients disappear in a short time after surgery, laparoscopic
      antireflux surgery should also be considered from pneumological aspects. There
      are no individual predictors for the success of antireflux surgery, only the sum
      of all relevant individual case history and clinical criteria, as they are
      combined in the used score, can provide a reliable indication for surgery.

PMID- 25377518
TI  - [Transcardiac Access Routes for Endovascular Treatment of Ascending Aortic
      Pathologies].
AB  - Gold standard for treatment of pathologies of the ascending aorta is still open
      surgery with extracorporal circulation in moderate to deep hypothermia. These
      procedures are associated with high morbidity and mortality, especially if
      performed in older patients or after previous cardiac surgery. Thoracic
      endovascular aortic repair (TEVAR) has become the preferred treatment option for
      thoracic aortic pathologies of the descending aorta even in high-risk patients
      with severe comorbidities resulting in reduced morbidity and mortality compared
      to open repair. Despite the continuous development of endograft technology an
      adequate arterial access still poses a relevant limitation of this treatment
      option accentuated in the proximal segments of the aorta. The transfemoral access
      may be limited due to severe kinking or arteriosclerotic plaque stenosis of
      femoral or iliac vessels. Furthermore, the long distance between femoral access
      vessels and the aortic lesion impairs device torsibility and exact deployment of
      the stent graft. To provide a practical alternative endovascular access to the
      ascending aorta, antegrade transcardiac access routes including transapical or
      transseptal techniques have recently gained increasing interest. 

PMID- 25377516
TI  - Influence of hepatitis B virus reactivation on the recurrence of HBV-related
      hepatocellular carcinoma after curative resection in patients with low viral
      load.
AB  - It is unclear whether the reactivation of hepatitis B virus (HBV) influences the
      prognosis of hepatocellular carcinoma (HCC) after resection in patients with
      chronic hepatitis B. The aim of this study was to identify the influence of HBV
      reactivation on the recurrence of hepatitis B-related HCC after curative
      resection in patients with low viral load (HBV DNA <2000 IU/mL). We
      retrospectively analysed a total of 130 patients who underwent curative resection
      for HBV-related early stage HCC (single nodule; <5 cm/two or three nodules; <3
      cm) with pre-operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The
      predictive factors including HBV reactivation for the recurrence of HBV-related
      HCC after curative resection were investigated. Fifty-three patients (41%) had
      HBV reactivation after resection among 130 patients. HBV reactivation was
      observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77
      patients with detectable baseline HBV DNA. Cumulative recurrence rates after
      resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The
      multivariable analysis demonstrated that the risk factors for the recurrence were
      the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003),
      multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03,
      P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after
      curative resection is associated with the recurrence of HBV-related HCC in
      patients with low viral load.

PMID- 25377519
TI  - Treatment of wet age-related macular degeneration by ranibizumab in "real life"
      in France: treatment behaviours and associated visual outcome.

PMID- 25377520
TI  - A geographical cluster randomised stepped wedge study of continuing medical
      education and cancer diagnosis in general practice.
AB  - BACKGROUND: Denmark has inferior cancer survival rates compared with many
      European countries. The main reason for this is suggested to be late diagnosis at
      advanced cancer stages. Cancer diagnostic work-up begins in general practice in
      85% of all cancer cases. Thus, general practitioners (GPs) play a key role in the
      diagnostic process. The latest Danish Cancer Plan included continuing medical
      education (CME) on early cancer diagnosis in general practice to improve early
      diagnosis. This dual aims of this protocol are, first, to describe the
      conceptualisation, operationalisation and implementation of the CME and, second,
      to describe the study design and outcomes chosen to evaluate the effects of the
      CME. METHODS/DESIGN: The intervention is a CME in early cancer diagnosis
      targeting individual GPs. It was developed by a step-wise approach. Barriers for
      early cancer diagnosis at GP level were identified systematically and analysed
      using the behaviour system involving capability, opportunity and motivation
      described by Michie et al. The study will be designed as a geographical cluster
      randomised stepped wedge study. The study population counts 836 GPs from 417
      general practices in the Central Denmark Region, geographically divided into
      eight clusters. GPs from each cluster will be invited to a CME meeting at a
      certain date three weeks apart. The primary outcomes will be primary care
      interval and GP referral rate on cancer suspicion. Data will be obtained from
      national registries, GP-completed forms on patients referred to cancer fast-track
      pathways and GP-completed online questionnaires before and after the
      intervention. DISCUSSION: To our knowledge, this will be the first study to
      measure the effect of a theory-based CME in early cancer diagnosis at three
      levels: GP knowledge and attitude, GP activity and patient outcomes. The achieved
      knowledge will contribute to the understanding of whether and how general
      practice's ability to perform cancer diagnosis may be improved. TRIAL
      REGISTRATION: Registered as NCT02069470 on ClinicalTrials.gov.

PMID- 25377521
TI  - Anti-JC Virus Antibody Prevalence in Canadian MS Patients.
AB  - BACKGROUND: Anti-John Cunningham (JCV) antibodies have been detected in
      approximately 50% to 60% of multiple sclerosis (MS) patients. Age, sex, and
      geographic location have been associated with seroprevalence differences. We
      describe anti-JCV antibody prevalence in the Canadian cohort of patients enrolled
      in the JCV Epidemiology in MS study. METHODS: This cross-sectional multicenter
      study evaluated the effects of demographic and disease characteristics on anti
      JCV antibody seroprevalence in MS patients irrespective of disease type and
      treatment. A single blood sample was collected for analysis of anti-JCV
      antibodies using a two-step enzyme-linked immunosorbent assay (ELISA). Chi-square
      and logistic regression tests were used to determine significance. RESULTS: A
      total of 4198 Canadian MS patients participated in the study; the overall anti
      JCV antibody prevalence was 56.3% (95% confidence interval: 54.8% to 57.8%).
      Seroprevalence was significantly associated with age (increasing from 45% in
      young to 61% in those >60 years), sex, and region (p<0.0001 for age and sex;
      p=0.005 for region). No significant differences in anti-JCV antibody prevalence
      were associated with race, MS disease type and duration, or number and duration
      of treatments. Immunosuppressant use was associated with a higher seroprevalence
      rate (63.4%) compared with no immunosuppressant use (55.9%; p=0.040).
      CONCLUSIONS: Canadian MS patients had an overall anti-JCV antibody seroprevalence
      that was consistent with previous studies using the two-step ELISA. Significant
      associations of anti-JCV antibody positivity were found with age, sex, region,
      and immunosuppressant therapy, whereas seroprevalence was not associated with
      race, MS type, MS duration, or number or duration of MS treatments.

PMID- 25377523
TI  - Co-victims of Homicide: A Systematic Review of the Literature.
AB  - This systematic literature review examines the effects of homicide on surviving
      family members, the "co-victims" or "survivors" of homicide. A content analysis
      was conducted on 40 articles identified through a search of the literature. The
      research samples were predominately located in the United States, but included
      two U.K. samples, one Jamaican sample, and one sample from Israel. All articles
      were written in English. Three themes were identified. Nineteen articles explored
      the psychological, academic, social, occupational, and familial effects of
      homicide. Thirteen articles considered survivors' grieving process and how it was
      altered by experiences with the criminal justice system as well as coping
      strategies used by survivors to deal with their grief. Eight articles explored
      treatment interventions available to help surviving family members deal with
      their grief. Key findings from the articles, limitations of the current research,
      and implications for future research, policy, and practice are included. 

PMID- 25377522
TI  - Impact of lithium alone and in combination with antidepressants on cytokine
      production in vitro.
AB  - Lithium is an important psychopharmacological agent for the treatment of unipolar
      as well as bipolar affective disorders. Lithium has a number of side effects such
      as hypothyroidism and aggravation of psoriasis. On the other hand, lithium has
      pro-inflammatory effects, which appear beneficial in some disorders associated
      with immunological deficits, such as human immunodeficiency virus (HIV) infection
      and systemic lupus erythematosus (SLE). Therefore, immunological characteristics
      of lithium may be an important consideration in individualized therapeutic
      decisions. We measured the levels of the cytokines interleukin (IL)-1beta, IL-2,
      IL-4, IL-6, IL-22, IL-17 and tumour necrosis factor (TNF)-alpha in the stimulated
      blood of thirty healthy subjects supplemented with lithium alone, the
      antidepressants citalopram, escitalopram or mirtazapine alone, the combination of
      each antidepressant with lithium, and a no drug control. These drugs were tested
      under three blood stimulant conditions: murine anti-human CD3 monoclonal antibody
      OKT3 and the 5C3 monoclonal antibody (OKT3/5C3), phytohemagglutinin (PHA), and
      unstimulated blood. Lithium, alone and in combination with any of the tested
      antidepressants, led to a consistent increase of IL-1beta, IL-6 and TNF-alpha
      levels in the unstimulated as well as the stimulated blood. In the OKT3/5C3- and
      PHA-stimulated blood, IL-17 production was significantly enhanced by lithium.
      Lithium additionally increased IL-2 concentrations significantly in PHA
      stimulated blood. The data support the view that lithium has pro-inflammatory
      properties. These immunological characteristics may contribute to side effects of
      lithium, but may also explain its beneficial effects in patients suffering from
      HIV infection or SLE. 

PMID- 25377524
TI  - Contribution of genetics to ecological restoration.
AB  - Ecological restoration of degraded ecosystems has emerged as a critical tool in
      the fight to reverse and ameliorate the current loss of biodiversity and
      ecosystem services. Approaches derived from different genetic disciplines are
      extending the theoretical and applied frameworks on which ecological restoration
      is based. We performed a search of scientific articles and identified 160
      articles that employed a genetic approach within a restoration context to shed
      light on the links between genetics and restoration. These articles were then
      classified on whether they examined association between genetics and fitness or
      the application of genetics in demographic studies, and on the way the studies
      informed restoration practice. Although genetic research in restoration is
      rapidly growing, we found that studies could make better use of the extensive
      toolbox developed by applied fields in genetics. Overall, 41% of reviewed studies
      used genetic information to evaluate or monitor restoration, and 59% provided
      genetic information to guide prerestoration decision-making processes. Reviewed
      studies suggest that restoration practitioners often overlook the importance of
      including genetic aspects within their restoration goals. Even though there is a
      genetic basis influencing the provision of ecosystem services, few studies
      explored this relationship. We provide a view of research gaps, future directions
      and challenges in the genetics of restoration. 

PMID- 25377525
TI  - Effect of capping agent concentration on thermoluminescence and photoluminescence
      of copper-doped zinc sulfide nanoparticles.
AB  - Copper-doped zinc sulfide (ZnS:Cu) nanoparticles with varying concentrations of
      capping agent were prepared using a chemical route technique. These particles
      were characterized by scanning electron microscopy (SEM), transmission electron
      microscopy and X-ray diffraction (XRD). Optical absorption studies showed that
      the absorption edge shifted towards the blue region as the concentration of the
      capping agent increased. Using effective mass approximation, calculation of the
      nanoparticle size indicated that effective band gap energy increases with
      decreasing particle size. The thermoluminescence (TL) properties of sodium
      hexameta phosphate (SHMP)-passivated ZnS:Cu nanoparticles were investigated after
      UV irradiation at room temperature. The TL glow curve of capped ZnS:Cu showed
      variations in TL peak position and intensity with the change in capping agent
      concentration. The photoluminescence (PL) spectra of ZnS:Cu nanoparticles excited
      at 254 nm exhibited a broad green emission band peaking around 510 nm, which
      confirmed the characteristic feature of Zn(2+) as well as Cu(2+) ions as the
      luminescent centres in the lattice. The PL spectra of ZnS:Cu nanoparticles with
      increasing capping agent concentrations revealed that the emission becomes more
      intense and shifted towards shorter wavelengths as the sizes of the samples were
      reduced.

PMID- 25377526
TI  - Peptide-induced hierarchical long-range order and photocatalytic activity of
      porphyrin assemblies.
AB  - Long-range structural order and alignment over different scales are of key
      importance for the regulation of structure and functionality in biology. However,
      it remains a great challenge to engineer and assemble such complex functional
      synthetic systems with order over different length scales from simple
      biologically relevant molecules, such as peptides and porphyrins. Herein we
      describe the successful introduction of hierarchical long-range order in
      dipeptide-adjusted porphyrin self-assembly by a thermodynamically driven self
      orienting assembly pathway associated with multiple weak interactions. The long
      range order and alignment of fiber bundles induced new properties, including
      anisotropic birefringence, a large Stokes shift, amplified chirality, and
      excellent photostability as well as sustainable photocatalytic activity. We also
      demonstrate that the aligned fiber bundles are able to induce the epitaxially
      oriented growth of Pt nanowires in a photocatalytic reaction. 

PMID- 25377527
TI  - A mechanically robust and highly ion-conductive polymer-blend coating for high
      power and long-life lithium-ion battery anodes.
AB  - A mechanically robust and ion-conductive polymeric coating containing two
      polymers, polyethylene glycol tert-octylphenyl ether and poly(allyl amine), with
      four tailored functional groups is developed for graphite and graphite-Si
      composite anodes. The coating, acting as an artificial solid electrolyte
      interphase, leads to remarkable enhancement in capacity reversibility and cycling
      stability, as well as a high-rate performance of the studied anodes. 

PMID- 25377528
TI  - Concentration and pattern changes of porcine serum apolipoprotein A-I in four
      different infectious diseases.
AB  - Apolipoprotein A-I (Apo A-I) is a major protein in lipid/lipoprotein metabolism
      and decreased serum levels have been observed in many species in response to
      inflammatory and infectious challenges. Little is known about the porcine
      homologue, therefore in this work we have characterized it through biochemical
      and proteomic techniques. In 2DE, porcine serum Apo A-I is found as three spots,
      the two more acidic ones corresponding to the mature protein, the more basic spot
      to the protein precursor. Despite high sequence coverage in LC-MS/MS, we did not
      find a sequence or PTM difference between the two mature protein species. Besides
      this biochemical characterization, we measured overall levels and relative
      species abundance of serum Apo A-I in four different viral and bacterial porcine
      infectious diseases. Lower overall amounts of Apo A-I were observed in Salmonella
      typhimurium and Escherichia coli infections. In the 2DE protein pattern, an
      increase of the protein precursor together with a lower level of mature protein
      species were detected in the porcine circovirus type 2-systemic disease and S.
      typhimurium infection. These results reveal that both the porcine serum Apo A-I
      concentration and the species pattern are influenced by the nature of the
      infectious disease. 

PMID- 25377529
TI  - Acid-sensing ion channels promote the inflammation and migration of cultured rat
      microglia.
AB  - Microglia, the major immune cells in central nervous system, act as the
      surveillance and scavenger of immune defense and inflammatory response. Previous
      studies suggest that there might be close relationship between acid-sensing ion
      channels (ASICs) and inflammation, however, the exact role of ASICs in microglia
      during inflammation remains elusive. In the present study, we identified the
      existence of ASICs in the primary cultured rat microglia and explored their
      functions. By using reverse transcriptase polymerase chain reaction (RT-PCR),
      quantitative real-time PCR (qPCR), western blotting, and immunofluorescence
      experiments, we demonstrated that ASIC1, ASIC2a, and ASIC3 were existed in
      cultured and in situ rat microglia. After lipopolysaccharide (LPS) stimulation,
      the expressions of microglial ASIC1 and ASIC2a were upregulated. Meanwhile, ASIC
      like currents and acid-induced elevation of intracellular calcium were increased,
      which could be inhibited by the nonspecific ASICs antagonist amiloride and
      specific homomeric ASIC1a blocker PcTx1. In addition, both inhibitors reduced the
      expression of inflammatory cytokines, including inducible nitric oxide synthase
      and cyclooxygenase 2 stimulated by LPS. Furthermore, we also observed significant
      increase in the expression of ASIC1 and ASIC2a in scrape-stimulated microglial
      migration. Amiloride and PcTx1 prevented the migration by inhibiting ERK
      phosphorylation. Taken together, these results suggest that ASICs participate in
      neuroinflammatory response, which will provide a novel therapeutic strategy for
      controlling the inflammation-relevant neuronal diseases.

PMID- 25377531
TI  - American parent perspectives on quality of life in pediatric cochlear implant
      recipients.
AB  - OBJECTIVES: Cochlear implantation influences not only communication but also
      psychosocial outcomes in children with severe to profound hearing loss. Focusing
      on issues specific to cochlear implantation (e.g., self-reliance, social
      relations, education, effects of implantation, and supporting the child) may
      provide a more accurate and relative view of functional status of pediatric
      cochlear implant (CI) recipients. The present study analyzes parental
      perspectives of CI-specific health-related quality of life (HRQoL) in children
      with CIs to determine (a) if parents differentially rate their child's quality of
      life according to psychosocial domain (e.g., communication, self-reliance,
      education); (b) if associations exist between quality of life domains specific to
      cochlear implantation in pediatric implant recipients; and (c) if demographic
      variables (i.e., chronologic age, age at cochlear implantation, duration of
      device experience) mediate parent ratings of quality of life in pediatric CI
      recipients. DESIGN: Parents of 33 children with CIs (mean age, 9.85 years; mean
      age of CI activation, 2.47 years; mean device experience, 7.47 years) completed a
      validated condition-specific questionnaire, Children With Cochlear Implants:
      Parental Perspectives. RESULTS: Parents positively rated most HRQoL domains,
      although education and effects of implantation received significantly less
      positive ratings (p < 0.01). Three domains (communication, self-reliance, and
      well-being) significantly correlated with at least 5 other domains, suggesting
      that positivity in one domain co-occurs with positivity in other domains.
      Demographic variables (chronologic age, CI activation age, and duration of CI
      use) did not correlate significantly with psychosocial outcomes; rather, parents
      reported positive HRQoL and successful functional use of CI across demographic
      variables. CONCLUSIONS: Parents of children and adolescents with CIs rate overall
      HRQoL positively across psychosocial domains. Significantly less positive ratings
      of education and effects of implantation may result from limited access to CI
      related accommodations and varying parent expectations, warranting further
      exploration to maximize psychosocial and performance outcomes in pediatric CI
      users.

PMID- 25377532
TI  - Mortality benefits of population-wide adherence to national physical activity
      guidelines: a prospective cohort study.
AB  - We quantified the mortality benefits and attributable fractions associated with
      engaging in physical activity across a range of levels, including those
      recommended by national guidelines. Data were from the Allied Dunbar National
      Fitness Survey, a population-based prospective cohort comprising 1,796 male and
      2,122 female participants aged 16-96 years, randomly selected from 30 English
      constituencies in 1990. Participants were tagged for mortality at the Office for
      National Statistics. Cox multivariable regression quantified the association
      between self-reported achievement of activity guidelines--150 min of at least
      moderate activity per week, equivalent here to 30 or more 20-min episodes of at
      least moderate activity per month--and mortality adjusting for age, sex, smoking
      status, social class, geographical area, anxiety/depression and interview season.
      There were 1,175 deaths over a median (IQR) of 22.9 (3.9) years follow-up; a
      mortality rate of 15.2, 95% confidence interval (CI) 14.4-16.1 per 1,000 person
      years. Compared with being inactive (no 20-min bouts per month), meeting activity
      guidelines (30+ bouts) was associated with a 25% lower mortality rate, adjusting
      for measured confounders. If everyone adhered to recommended-, or even low
      activity levels, a substantial proportion of premature mortality might be avoided
      (PAF, 95% CI 20.6, 6.9-32.3 and 8.9, 4.2-13.4%, respectively). Among a
      representative English population, adherence to activity guidelines was
      associated with significantly reduced mortality. Efforts to increase population
      wide activity levels could produce large public health benefits and should remain
      a focus of health promotion efforts.

PMID- 25377534
TI  - Should non-cardiovascular mortality be considered in the SCORE model? Findings
      from the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort.
AB  - Competing non-cardiovascular related deaths were not accounted for in the
      Systematic COronary Risk Evaluation (SCORE) model. In this study we assessed the
      impact of non-cardiovascular related deaths on the prognostic performance and
      yield of the SCORE model. 5,752 participants from the Prevention of Renal and
      Vascular End stage Disease cohort aged 40 years and older who were free of
      atherosclerotic cardiovascular disease (CVD) at baseline were included. A cause
      specific hazards (CSH) CVD-related mortality prediction model that accounted for
      non-CVD-related deaths was developed. The prognostic performance of this model
      was then compared with a refitted SCORE model. During a median follow-up period
      of 12.5 years, 139 CVD and 495 non-CVD-related deaths were reported.
      Discriminatory performance was comparable between the models (C-index = 0.64).
      The models showed good calibration although the CSH model underestimated risk in
      the highest decile while the refitted SCORE model showed overestimation. The CSH
      model classified more non-events into the low risk group compared to the refitted
      SCORE model (n = 51), yet it was accompanied by a misclassification of six events
      into the low risk group. The refitted SCORE model classified more individuals as
      high risk. However, the potential overtreatment that may result from utilizing
      the refitted SCORE model, when compared with the CSH model, still falls within
      acceptable limits. Our findings do not support the incorporation of non
      cardiovascular mortality into the estimation of total cardiovascular risk in the
      SCORE model.

PMID- 25377533
TI  - Fish consumption and mortality in the European Prospective Investigation into
      Cancer and Nutrition cohort.
AB  - Fish is a source of important nutrients and may play a role in preventing heart
      diseases and other health outcomes. However, studies of overall mortality and
      cause-specific mortality related to fish consumption are inconclusive. We
      examined the rate of overall mortality, as well as mortality from ischaemic heart
      disease and cancer in relation to the intake of total fish, lean fish, and fatty
      fish in a large prospective cohort including ten European countries. More than
      500,000 men and women completed a dietary questionnaire in 1992-1999 and were
      followed up for mortality until the end of 2010. 32,587 persons were reported
      dead since enrolment. Hazard ratios and their 99% confidence interval were
      estimated using Cox proportional hazard regression models. Fish consumption was
      examined using quintiles based on reported consumption, using moderate fish
      consumption (third quintile) as reference, and as continuous variables, using
      increments of 10 g/day. All analyses were adjusted for possible confounders. No
      association was seen for fish consumption and overall or cause-specific mortality
      for both the categorical and the continuous analyses, but there seemed to be a U
      shaped trend (p < 0.000) with fatty fish consumption and total mortality and with
      total fish consumption and cancer mortality (p = 0.046).

PMID- 25377535
TI  - Socio-economic status and co-morbidity as risk factors for trauma.
AB  - Clinical experience and previous studies indicate that low socioeconomic
      positions are overrepresented in trauma populations. The reason for this social
      variation in injury risk is likely to be multifactorial. Both individual and
      environmental sources of explanation are plausible to contribute. We investigated
      the impact of the influence of socioeconomic factors and co-morbidity on the risk
      of becoming a trauma victim in a case-control study including 7,382 trauma
      patients matched in a one to five ratio with controls matched by age-, gender-
      and municipality from a level 1 trauma centre. Data from the trauma cohort were
      linked to national registries. Associations between socioeconomic factors and co
      morbidity were estimated by conditional logistic regression. The trauma patients
      had been treated for psychiatric, substance abuse and somatic diagnoses to a
      higher extent than the controls. In the conditional logistic regression analysis
      a low level of education and income as well as co-morbidity (divided into
      psychiatric, substance abuse and somatic diagnoses) were all independent risk
      factors for trauma. Analysing patients with an injury severity score >15
      separately did not alter the results, except for somatic diagnoses not being a
      risk factor. Recent treatment for substance abuse significantly increased the
      risk for trauma. Low level of education and income as well as psychiatric,
      substance abuse and somatic co-morbidity were all independent risk factors for
      trauma. Active substance abuse strongly influenced the risk for trauma and had a
      time dependent pattern. These insights can facilitate future implementation of
      injury prevention strategies tailored to specific risk groups. 

PMID- 25377536
TI  - Influence of Carotino oil on in vitro rumen fermentation, metabolism and apparent
      biohydrogenation of fatty acids.
AB  - The study appraised the effects of Carotino oil on in vitro rumen fermentation,
      gas production, metabolism and apparent biohydrogenation of oleic, linoleic and
      linolenic acids. Carotino oil was added to a basal diet (50% concentrate and 50%
      oil palm frond) at the rate of 0, 2, 4, 6 and 8% dry matter of the diet. Rumen
      inoculum was obtained from three fistulated Boer bucks and incubated with 200 mg
      of each treatment for 24 h at 39 degrees C. Gas production, fermentation
      kinetics, in vitro organic matter digestibility (IVOMD), volatile fatty acids
      (VFA), in vitro dry matter digestibility (IVDMD), metabolizable energy and free
      fatty acids were determined. Carotino oil did not affect (P > 0.05) gas
      production, metabolizable energy, pH, IVOMD, IVDMD, methane, total and individual
      VFAs. However, Carotino oil decreased (P < 0.05) the biohydrogenation of linoleic
      and linolenic acids but enhanced (P < 0.05) the biohydrogenation of oleic acid.
      After 24 h incubation, the concentrations of stearic, palmitic, pentadecanoic,
      myristic, myristoleic and lauric acids decreased (P < 0.05) while the
      concentration of linolenic, linoleic, oleic and transvaccenic acids and
      conjugated linoleic acid (CLAc9t11) increased (P < 0.05) with increasing levels
      of Carotino oil. Carotino oil seems to enhance the accumulation of beneficial
      unsaturated fatty acids without disrupting rumen fermentation. 

PMID- 25377537
TI  - A mini-midwifery business institute in a midwifery professional roles course: an
      innovative teaching strategy for successful career planning and business
      management of practice.
AB  - It is essential to include teaching strategies in midwifery education that
      address career planning and the business aspects of practice. This article
      presents the Mini-Midwifery Business Institute (M-MBI), an innovative teaching
      strategy for midwives that can also be applied to other advanced practice
      professions. The M-MBI can be integrated into a professional roles course. Before
      and after graduation, midwifery students and other advanced practice
      professionals can use the information to gain confidence and skills for
      successful career planning and the business management of practice. 

PMID- 25377538
TI  - Should aspirin be used for the primary prevention of cardiovascular disease in
      the general population?

PMID- 25377540
TI  - Optimal therapy in hepatitis C virus liver transplant patients with direct acting
      antivirals.
AB  - Hepatitis C virus (HCV) end stage liver disease is a main indication for liver
      transplantation (LT). Recurrent HCV always occurs when patients are transplanted
      with a detectable viral load, leading to cirrhosis in 20-30% of patients within 5
      years. Achieving a sustained virological response (SVR) with antiviral treatment
      is the only way to improve patient and graft survival. Dual therapy based on
      pegylated interferon and ribavirin (PEG-IFN/RBV) was the standard of care for
      many years with limited efficacy and a poor safety profile. The addition of first
      generation NS3/4 protease inhibitors (PI) improved SVR rates from 30 to 50-60%.
      But the occurrence of serious adverse events and drug-drug interactions with
      calcineurin inhibitors have both been limiting factors for their use during LT.
      The preliminary results of the use of second generation direct acting antivirals
      (DAA) in transplant patients showed better efficacy with an SVR rate >70%. The
      pre- and post-transplantation safety profile is good. Although fewer drug-drug
      interactions are expected, some new DAA still interact with immunosuppressive
      drugs. Certain questions such as the use of RBV or the optimal duration of
      therapy have still not been resolved but should be answered by the many ongoing
      studies in the coming year.

PMID- 25377539
TI  - Echinacea purpurea up-regulates CYP1A2, CYP3A4 and MDR1 gene expression by
      activation of pregnane X receptor pathway.
AB  - 1.This study investigated the mechanism underlying Echinacea-mediated induction
      of CYP1A2, CYP3A4 and MDR1 in terms of human pregnane X receptor (PXR)
      activation. 2.Crude extracts and fractions of Echinacea purpurea were tested for
      PXR activation in HepG2 cells by a reporter gene assay. Quantitative real-time
      PCR was carried out to determine their effects on CYP1A2 and CYP3A4 mRNA
      expressions. Capsules and fractions were risk ranked as high, intermediate and
      remote risk of drug-metabolizing enzymes induction based on EC50 values
      determined for respective CYPs. 3. Fractions F1, F2 and capsule (2660) strongly
      activated PXR with 5-, 4- and 3.5-fold increase in activity, respectively.
      Echinacea preparations potentiated up-regulation of CYP1A2, CYP3A4 and MDR1 via
      PXR activation. 4.Thus E. purpurea preparations cause herb-drug interaction by up
      regulating CYP1A2, CYP3A4 and P-gp via PXR activation.

PMID- 25377541
TI  - A case of anti-NMDAR encephalitis induced by ovarian teratoma.
AB  - A young woman was received in the hospital with gradually worsening neurological
      symptoms consistent with encephalitis. After several cerebrospinal fluid
      examinations, infectious encephalitis (viral, bacterial, or linked to
      tuberculosis or parasites) and autoimmune encephalitis were ruled out. The
      possibility of autoantibody-mediated encephalitis was considered, and anti-N
      methyl-D-aspartate receptor (anti-NMDAR) antibodies were detected in
      cerebrospinal fluid and blood, thus confirming the diagnosis of anti-NMDAR
      encephalitis. After initial successful treatment, the disease relapsed and the
      repeated ultrasound investigation revealed teratoma in the left ovary, which was
      not observed at initial examination. Tumor was removed by laparoscopic
      oophorocystectomy, and the treatment with hormones and gamma globulin was
      continued after the surgery. The patient's conditions were gradually improving
      after the treatment. Correct diagnostic and prompt treatment of anti-NMDAR
      encephalitis remains a serious clinical challenge due to its unspecific
      manifestations and varying response to treatments. This article describes the
      details of a recent complicated case of a patient with this condition. The
      information will be of interest to clinicians working with encephalitis patients.

PMID- 25377542
TI  - Protective effects of Wusen Erlian granules in experimental model of viral
      myocarditis.
AB  - We wished to study the protective effects of Wusen Erlian granules, a therapy
      from traditional Chinese medicine, in experimental viral myocarditis (VMC). Sixty
      mice were divided into six groups: control group, infection group, ribavirin
      group, and three Wusen Erlian groups, treated with low, intermediate, or high
      doses (4, 12, or 20 mg/kg) of Wusen Erlian. Control animals were
      intraperitoneally injected with culture medium, while animals in other groups
      received intraperinoneal injections of CoxB3 virus. The Wusen Erlian granules
      were intragastrically administered on days 0, 1, 2, 3, 4, and 5 after virus
      inoculation. The experiment was terminated 2 h after the final drug
      administration. The mice were weighed, and specimens were collected for detection
      of myocardial enzymes, measurement of organ index, and natural killer (NK) cell
      activity. The levels of creatine kinase isoenzyme, troponin, and myoglobin were
      significantly increased in infected animals (all p < 0.05). Compared with
      infection group, the levels of creatine kinase isoenzyme and troponin were
      significantly (p < 0.05) decreased in animals that received ribavirin, and in
      animals that received high or intermediate dose of Wusen Erlian. Furthermore, the
      spleen and thymus indexes were increased in animals treated with ribavirin, or
      high/intermediate doses of Wusen Erlian, suggesting immunoregulating functions of
      these drugs. The NK cell activity was also markedly increased in the above three
      groups. Wusen Erlian alleviates the CoxB3-induced myocardial injury and exhibits
      immunoregulating features, leading to protective effects toward myocardial cells
      in experimental VMC. 

PMID- 25377543
TI  - Grading of peripheral cytopenias caused by nonalcoholic cirrhotic portal
      hypertension and its clinical significance.
AB  - This study investigates peripheral cytopenias in patients with splenomegaly
      caused by nonalcoholic cirrhotic portal hypertension. Data from 330 splenomegaly
      cases caused by nonalcoholic cirrhotic portal hypertension were collected and
      analyzed using univariate and multivariate analysis. The cytopenias were scored
      and graded according to the F value of the multiple linear regression equation.
      Based on the severity of thrombocytopenia, cytopenia was graded as mild,
      moderate, or severe, and determined by a score of <2 points, 2-3 points, and >3
      points. 30 % of the patients had monolineage cytopenias, 35.8 % had bilineage
      cytopenias, and 34.2 % had trilineage cytopenias. All patients were treated
      surgically. In the univariate analysis, the severity of erythropenia was
      different in the surgical outcome when compared to the intra-group (P < 0.05). In
      the multivariate analysis, thrombocytopenia was different in the surgical
      outcomes when compared with leukopenia and erythropenia (P < 0.05). There was a
      significant difference in surgical outcomes between the three grades (mild,
      moderate, and severe) of cytopenia (P < 0.05). Peripheral cytopenias have a
      significant impact on the clinical outcomes. The more severe the cytopenias, the
      worse the surgical outcomes are. Thrombocytopenia is a major factor influencing
      surgical outcomes. The thrombocytopenia-based three-level grading of cytopenias
      provides a basis for analyzing individual cases, planning treatment, and
      assessing prognosis in clinical practice.

PMID- 25377545
TI  - Calcipotriol pretreatment enhances methyl aminolevulinate-induced protoporphyrin
      IX: an in vivo study in hairless mice.

PMID- 25377544
TI  - Immunolabeling of gamma-glutamyl transferase 5 in normal human tissues reveals
      that expression and localization differ from gamma-glutamyl transferase 1.
AB  - Gamma-glutamyl transferase (GGT5) was discovered due to its ability to convert
      leukotriene C4 (LTC4, a glutathione S-conjugate) to LTD4 and may have an
      important role in the immune system. However, it was not known which cells
      express the enzyme in humans. We have developed a sensitive and specific antibody
      that can be used to detect human GGT5 on Western blots and in fixed tissue
      sections. We localized GGT5 expression in normal human tissues. We observed GGT5
      expressed by macrophages present in many tissues, including tissue-fixed
      macrophages such as Kupffer cells in the liver and dust cells in the lung. GGT5
      was expressed in some of the same tissues that have been shown to express gamma
      glutamyl transferase (GGT1), the only other enzymatically active protein in this
      family. But, the two enzymes were often expressed by different cell types within
      the tissue. For example, GGT5 was expressed by the interstitial cells of the
      kidney, whereas GGT1 is expressed on the apical surface of the renal proximal
      tubules. Other tissues with GGT5-positive cells included: adrenal gland, salivary
      gland, pituitary, thymus, spleen, liver, bone marrow, small intestine, stomach,
      testis, prostate and placenta. GGT5 and GGT1 are cell surface enzymes. The
      different pattern of expression results in their access to different
      extracellular fluids and therefore different substrates. GGT5 has access to
      substrates in blood and intercellular fluids, while GGT1 has access primarily to
      fluids in ducts and glands throughout the body. These data provide new insights
      into the different functions of these two related enzymes.

PMID- 25377546
TI  - Platinum(II) olefin hydroarylation catalysts: tuning selectivity for the anti
      Markovnikov product.
AB  - Pt(II) complexes containing unsymmetrical (pyridyl)pyrrolide ligands are shown to
      catalyze the hydroarylation of unactivated alkenes with selectivity for the anti
      Markovnikov product. Substitution on the pyrrolide portion of the ligand allows
      effective tuning of the selectivity to anti-Markovnikov alkylarene products,
      whereas substitution on the pyridyl portion can promote competitive alkenylarene
      production. 

PMID- 25377547
TI  - Exploring the complexity of quantum control optimization trajectories.
AB  - The control of quantum system dynamics is generally performed by seeking a
      suitable applied field. The physical objective as a functional of the field forms
      the quantum control landscape, whose topology, under certain conditions, has been
      shown to contain no critical point suboptimal traps, thereby enabling effective
      searches for fields that give the global maximum of the objective. This paper
      addresses the structure of the landscape as a complement to topological critical
      point features. Recent work showed that landscape structure is highly favorable
      for optimization of state-to-state transition probabilities, in that gradient
      based control trajectories to the global maximum value are nearly straight paths.
      The landscape structure is codified in the metric R >= 1.0, defined as the ratio
      of the length of the control trajectory to the Euclidean distance between the
      initial and optimal controls. A value of R = 1 would indicate an exactly straight
      trajectory to the optimal observable value. This paper extends the state-to-state
      transition probability results to the quantum ensemble and unitary transformation
      control landscapes. Again, nearly straight trajectories predominate, and we
      demonstrate that R can take values approaching 1.0 with high precision. However,
      the interplay of optimization trajectories with critical saddle submanifolds is
      found to influence landscape structure. A fundamental relationship necessary for
      perfectly straight gradient-based control trajectories is derived, wherein the
      gradient on the quantum control landscape must be an eigenfunction of the
      Hessian. This relation is an indicator of landscape structure and may provide a
      means to identify physical conditions when control trajectories can achieve
      perfect linearity. The collective favorable landscape topology and structure
      provide a foundation to understand why optimal quantum control can be readily
      achieved. 

PMID- 25377548
TI  - A medium throughput device to study the effects of combinations of surface
      strains and fluid-flow shear stresses on cells.
AB  - We report a medium throughput device to study the effects of combinations of two
      mechanical stimuli - surface strains and fluid flow shear stresses, on cells. The
      first generation prototype can screen combinations of five strain and five shear
      stress levels. Computational modeling and empirical measurements were used to
      determine the generated strains and flows. Uniform equibiaxial strains up to 20%
      and shear stresses up to 0.3 Pa can be generated. Compatibility of the device
      with cell culture and end point fixation, staining and imaging is shown using
      C2C12 mouse myoblast cells. 

PMID- 25377549
TI  - Stress exposure and postural control in young females.
AB  - The aim of this study was to determine if heightened stress had an adverse affect
      on the postural control of 14 young right-handed females during quiet standing in
      either the presence or the absence of visual input. The level of stress was
      evaluated by measuring the free cortisol response to awakening (cortisol
      awakening response; CAR) and by employing the perceived stress scale (PSS).
      Overall mood disturbance was measured using the profile of mood states (POMS).
      Postural control was evaluated using a force platform by measuring the 95%
      confidence ellipse area described by the center of pressure during 5 balance
      positions maintained for at least 52 sec, each with open and closed eyes. The
      results of this study revealed a significant positive correlation between CAR,
      PSS and POMS for each of the studied subjects. Furthermore, it was observed that
      whilst the level of stress was capable of influencing postural stability, this
      influence was particularly evident when no visual information was available.
      Additionally, it was determined that maintenance of posture is easier when the
      dominant foot is ahead, regardless of visual input.

PMID- 25377550
TI  - The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is
      essential for vascular development.
AB  - Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for
      embryonic development. Comparing different genetically engineered mouse models,
      we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1
      leads to lethal vascular defects with lack of proper investment with mural cells
      of both large and small vessels. We further demonstrate that LRP1 modulates Gi
      dependent sphingosine-1-phosphate (S1P) signaling and integrates S1P and PDGF-BB
      signaling pathways, which are both crucial for mural cell recruitment, via its
      intracellular domain. Loss of LRP1 leads to a lack of S1P-dependent inhibition of
      RAC1 and loss of constraint of PDGF-BB-induced cell migration. Our studies thus
      identify LRP1 as a novel player in angiogenesis and in the recruitment and
      maintenance of mural cells. Moreover, they reveal an unexpected link between
      lipoprotein receptor and sphingolipid signaling that, in addition to angiogenesis
      during embryonic development, is of potential importance for other targets of
      these pathways, such as tumor angiogenesis and inflammatory processes.

PMID- 25377551
TI  - TGFbeta signaling inhibits goblet cell differentiation via SPDEF in conjunctival
      epithelium.
AB  - The ocular surface epithelia, including the stratified but non-keratinized
      corneal, limbal and conjunctival epithelium, in concert with the epidermal
      keratinized eyelid epithelium, function together to maintain eye health and
      vision. Abnormalities in cellular proliferation or differentiation in any of
      these surface epithelia are central in the pathogenesis of many ocular surface
      disorders. Goblet cells are important secretory cell components of various
      epithelia, including the conjunctiva; however, mechanisms that regulate goblet
      cell differentiation in the conjunctiva are not well understood. Herein, we
      report that conditional deletion of transforming growth factor beta receptor II
      (Tgfbr2) in keratin 14-positive stratified epithelia causes ocular surface
      epithelial hyperplasia and conjunctival goblet cell expansion that invaginates
      into the subconjunctival stroma in the mouse eye. We found that, in the absence
      of an external phenotype, the ocular surface epithelium develops properly, but
      young mice displayed conjunctival goblet cell expansion, demonstrating that
      TGFbeta signaling is required for normal restriction of goblet cells within the
      conjunctiva. We observed increased expression of SAM-pointed domain containing
      ETS transcription factor (SPDEF) in stratified conjunctival epithelial cells in
      Tgfbr2 cKO mice, suggesting that TGFbeta restricted goblet cell differentiation
      directly by repressing Spdef transcription. Gain of function of Spdef in keratin
      14-positive epithelia resulted in the ectopic formation of goblet cells in the
      eyelid and peripheral cornea in adult mice. We found that Smad3 bound two
      distinct sites on the Spdef promoter and that treatment of keratin 14-positive
      cells with TGFbeta inhibited SPDEF activation, thereby identifying a novel
      mechanistic role for TGFbeta in regulating goblet cell differentiation.

PMID- 25377552
TI  - The sinus venosus contributes to coronary vasculature through VEGFC-stimulated
      angiogenesis.
AB  - Identifying coronary artery progenitors and their developmental pathways could
      inspire novel regenerative treatments for heart disease. Multiple sources of
      coronary vessels have been proposed, including the sinus venosus (SV),
      endocardium and proepicardium, but their relative contributions to the coronary
      circulation and the molecular mechanisms regulating their development are poorly
      understood. We created an ApjCreER mouse line as a lineage-tracing tool to map SV
      derived vessels onto the heart and compared the resulting lineage pattern with
      endocardial and proepicardial contributions to the coronary circulation. The data
      showed a striking compartmentalization to coronary development. ApjCreER-traced
      vessels contributed to a large number of arteries, capillaries and veins on the
      dorsal and lateral sides of the heart. By contrast, untraced vessels predominated
      in the midline of the ventral aspect and ventricular septum, which are vessel
      populations primarily derived from the endocardium. The proepicardium gave rise
      to a smaller fraction of vessels spaced relatively uniformly throughout the
      ventricular walls. Dorsal (SV-derived) and ventral (endocardial-derived) coronary
      vessels developed in response to different growth signals. The absence of VEGFC,
      which is expressed in the epicardium, dramatically inhibited dorsal and lateral
      coronary growth but left vessels on the ventral side unaffected. We propose that
      complementary SV-derived and endocardial-derived migratory routes unite to form
      the coronary vasculature and that the former requires VEGFC, revealing its role
      as a tissue-specific mediator of blood endothelial development.

PMID- 25377553
TI  - The Arabidopsis Mediator CDK8 module genes CCT (MED12) and GCT (MED13) are global
      regulators of developmental phase transitions.
AB  - Temporal coordination of developmental programs is necessary for normal ontogeny,
      but the mechanism by which this is accomplished is still poorly understood. We
      have previously shown that two components of the Mediator CDK8 module encoded by
      CENTER CITY (CCT; Arabidopsis MED12) and GRAND CENTRAL (GCT; Arabidopsis MED13)
      are required for timing of pattern formation during embryogenesis. A
      morphological, molecular and genomic analysis of the post-embryonic phenotype of
      gct and cct mutants demonstrated that these genes also promote at least three
      subsequent developmental transitions: germination, vegetative phase change, and
      flowering. Genetic and molecular analyses indicate that GCT and CCT operate in
      parallel to gibberellic acid, a phytohormone known to regulate these same three
      transitions. We demonstrate that the delay in vegetative phase change in gct and
      cct is largely due to overexpression of miR156, and that the delay in flowering
      is due in part to upregulation of FLC. Thus, GCT and CCT coordinate vegetative
      and floral transitions by repressing the repressors miR156 and FLC. Our results
      suggest that MED12 and MED13 act as global regulators of developmental timing by
      fine-tuning the expression of temporal regulatory genes.

PMID- 25377554
TI  - Two-pore channels function in calcium regulation in sea star oocytes and embryos.
AB  - Egg activation at fertilization is an excellent process for studying calcium
      regulation. Nicotinic acid adenine dinucleotide-phosphate (NAADP), a potent
      calcium messenger, is able to trigger calcium release, likely through two-pore
      channels (TPCs). Concomitantly, a family of ectocellular enzymes, the ADP-ribosyl
      cyclases (ARCs), has emerged as being able to change their enzymatic mode from
      one of nucleotide cyclization in formation of cADPR to a base-exchange reaction
      in the generation of NAADP. Using sea star oocytes we gain insights into the
      functions of endogenously expressed TPCs and ARCs in the context of the global
      calcium signals at fertilization. Three TPCs and one ARC were found in the sea
      star (Patiria miniata) that were localized in the cortex of the oocytes and eggs.
      PmTPCs were localized in specialized secretory organelles called cortical
      granules, and PmARCs accumulated in a different, unknown, set of vesicles,
      closely apposed to the cortical granules in the egg cortex. Using morpholino
      knockdown of PmTPCs and PmARC in the oocytes, we found that both calcium
      regulators are essential for early embryo development, and that knockdown of
      PmTPCs leads to aberrant construction of the fertilization envelope at
      fertilization and changes in cortical granule pH. The calcium signals at
      fertilization are not significantly altered when individual PmTPCs are silenced,
      but the timing and shape of the cortical flash and calcium wave are slightly
      changed when the expression of all three PmTPCs is perturbed concomitantly,
      suggesting a cooperative activity among TPC isoforms in eliciting calcium signals
      that may influence localized physiological activities.

PMID- 25377556
TI  - Heparan sulfate: a stem cell therapy target?
AB  - In this issue of Blood, Saez et al demonstrate that inhibition of heparan sulfate
      proteoglycan production by bone marrow osteolineage stromal cells results in
      hematopoietic stem cell egress from the bone marrow niche into the peripheral
      circulation.

PMID- 25377555
TI  - Repurposing an endogenous degradation system for rapid and targeted depletion of
      C. elegans proteins.
AB  - The capability to conditionally inactivate gene function is essential for
      understanding the molecular basis of development. In gene and mRNA targeting
      approaches, protein products can perdure, complicating genetic analysis. Current
      methods for selective protein degradation require drug treatment or take hours
      for protein removal, limiting their utility in studying rapid developmental
      processes in vivo. Here, we repurpose an endogenous protein degradation system to
      rapidly remove targeted C. elegans proteins. We show that upon expression of the
      E3 ubiquitin ligase substrate-recognition subunit ZIF-1, proteins tagged with the
      ZF1 zinc-finger domain can be quickly degraded in all somatic cell types examined
      with temporal and spatial control. We demonstrate that genes can be engineered to
      become conditional loss-of-function alleles by introducing sequences encoding the
      ZF1 tag into endogenous loci. Finally, we use ZF1 tagging to establish the site
      of cdc-42 gene function during a cell invasion event. ZF1 tagging provides a
      powerful new tool for the analysis of dynamic developmental events.

PMID- 25377557
TI  - Lymphotoxin-alpha keeps the gate open for T-cell infiltration in cHL.
AB  - In this issue of Blood, Fhu et al report that Reed-Sternberg cell-derived
      lymphotoxin-alpha activates endothelial cells to enhance T-cell recruitment in
      classical Hodgkin lymphoma (cHL), a process that is regulated by
      cyclooxygenase/nuclear factor-kappaB/activator protein 1 signaling pathways.

PMID- 25377558
TI  - Hit the spleen, JAK!
AB  - In this issue of Blood, Wang et al report on the response of splenic-derived
      hematopoietic stem and progenitor cells from patients with myelofibrosis (MF) to
      the Janus kinase (JAK) inhibitor, AZD1480.

PMID- 25377559
TI  - Leukemia cells make ruthless competitors.
AB  - In this issue of Blood, Kagoya et al provide evidence for an important role for
      factors secreted by leukemia cells in damaging and suppressing normal
      hematopoiesis.

PMID- 25377560
TI  - Identifying mutant pathways in the histiocytoses.
AB  - In this issue of Blood, the findings of Chakraborty et al and Emile et al support
      a model in which the mitogen-activated protein kinase (MAPK) and PI3K/AKT
      pathways are critical in the pathogenesis of 2 of the most common histiocytoses
      Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD)-whereas
      their respective mutational profiles demonstrate important similarities and
      differences.

PMID- 25377561
TI  - In contemporary patients with polycythemia vera, rates of thrombosis and risk
      factors delineate a new clinical epidemiology.

PMID- 25377562
TI  - Cryptic XPO1-MLLT10 translocation is associated with HOXA locus deregulation in T
      ALL.

PMID- 25377563
TI  - Two types of amyloid in a single heart.

PMID- 25377564
TI  - A germ line mutation in cathepsin B points toward a role in asparaginase
      pharmacokinetics.

PMID- 25377565
TI  - Bendamustine, etoposide, cytarabine, melphalan, and autologous stem cell rescue
      produce a 72% 3-year PFS in resistant lymphoma.

PMID- 25377566
TI  - Blockade of endothelial cell protein C receptor augments factor VIIa hemostatic
      effect in hemophilia treatment.

PMID- 25377567
TI  - Population pharmacokinetics of orally administered mefloquine in healthy
      volunteers and patients with uncomplicated Plasmodium falciparum malaria.
AB  - BACKGROUND: The determination of dosing regimens for the treatment of malaria is
      largely empirical and thus a better understanding of the
      pharmacokinetic/pharmacodynamic properties of antimalarial agents is required to
      assess the adequacy of current treatment regimens and identify sources of
      suboptimal dosing that could select for drug-resistant parasites. Mefloquine is a
      widely used antimalarial, commonly given in combination with artesunate. PATIENTS
      AND METHODS: Mefloquine pharmacokinetics was assessed in 24 healthy adults and 43
      patients with Plasmodium falciparum malaria administered mefloquine in
      combination with artesunate. Population pharmacokinetic modelling was conducted
      using NONMEM. RESULTS: A two-compartment model with a single transit compartment
      and first-order elimination from the central compartment most adequately
      described mefloquine concentration-time data. The model incorporated population
      parameter variability for clearance (CL/F), central volume of distribution (VC/F)
      and absorption rate constant (KA) and identified, in addition to body weight,
      malaria infection as a covariate for VC/F (but not CL/F). Monte Carlo simulations
      predict that falciparum malaria infection is associated with a shorter
      elimination half-life (407 versus 566 h) and T>MIC (766 versus 893 h).
      CONCLUSIONS: This is the first known population pharmacokinetic study to show
      falciparum malaria to influence mefloquine disposition. Protein binding, anaemia
      and other factors may contribute to differences between healthy individuals and
      patients. As VC/F is related to the earlier portion of the concentration-time
      profiles, which occurs during acute malaria, and CL/F is more related to the
      terminal phase during convalescence after treatment, this may explain why malaria
      was found to be a covariate for VC/F but not CL/F.

PMID- 25377568
TI  - Comment on: Antibiotic prophylaxis for transrectal prostate biopsy--a new
      strategy.

PMID- 25377570
TI  - [Reaction of bone tissue elements on synthetic bioresorbable materials based on
      lactic and glycolic acids].
AB  - The aim of the study was to evaluate the adverse effects of synthetic polymeric
      bioresorbable materials based on lactic and glycolic acids on the bone tissue.
      The study was carried-out on 40 Wister-line rats. Four types of bioresorbable
      polymeric materials were implanted: PolyLactide Glycolide Acid (PLGA), Poly-L
      Lactide Acid (PLLA); Poly-96L/4D-Lactide Acid (96/4 PLDLA); Poly-70L/30D-Lactide
      Acid (70/30 PLDLA). The results showed connective tissue formation
      (fibrointegration) bordering bone adjacent to implanted materials. This proved
      the materials to cause pathogenic influence on the bone which mechanisms are
      described in the article. 

PMID- 25377569
TI  - Imaging the distribution of polymyxins in the kidney.
AB  - OBJECTIVES: Dose-limiting nephrotoxicity remains the Achilles' heel of polymyxin
      B and polymyxin E (also known as colistin), which are important last-line
      antibiotics used against infections caused by MDR Gram-negative 'superbugs'. An
      understanding of the mechanisms of nephrotoxicity, including renal tissue
      distribution, is crucial for the development of safer polymyxin lipopeptide
      antibiotics. This is the first study to visualize the kidney distribution of
      polymyxin B using a mouse nephrotoxicity model and in situ immunostaining of
      kidney sections. METHODS: Polymyxin B nephrotoxicity in mice was induced over the
      course of 3 days (accumulated intravenous dose 175 mg/kg) and kidneys were
      harvested and frozen sectioned. The sections were fixed in cold acetone, dried
      and treated with 1% hydrogen peroxide. Endogenous mouse immunoglobulins were
      blocked and the tissue sections were treated with anti-polymyxin B mouse IgM
      antibody. The sections were incubated with a biotinylated anti-mouse secondary
      antibody conjugate followed by an Alexa Fluor 647-streptavidin conjugate.
      Polymyxin B distribution in the kidney sections was then visualized using a
      fluorescence scanning microscope. Kidney sections were also subjected to
      haematoxylin and eosin staining to assess pathological damage from the polymyxin
      induced nephrotoxicity. RESULTS: Immunostaining of kidney sections from a mouse
      with polymyxin B-induced nephrotoxicity revealed that polymyxin B distributed
      predominantly within the renal cortex. More specifically, polymyxin B accumulated
      within the proximal tubular cells. CONCLUSIONS: The observed accumulation of
      polymyxin B within proximal tubular cells is consistent with the extensive renal
      reabsorption of polymyxins and the likely cause of the associated nephrotoxicity.

PMID- 25377571
TI  - [Calcium and phosphorus content in erupted and impacted teeth enamel. The study
      in vivo].
AB  - This study shows that there are significant differences in the content of
      minerals in the enamel of the teeth to erupt in the near future after the
      eruption. Based on the data it can be concluded that immediately after the
      eruption of the tooth enamel entering the aggressive environment oral loses a
      certain amount of minerals. This explains the high dental caries is in the first
      fern years after the eruption. All figures are of high relevance in the planning
      of prevention. 

PMID- 25377572
TI  - [Evaluation of dental hard tissues by means of atomic force microscopy].
AB  - The paper presents modified method of teeth slice preparation for evaluating
      enamel and dentin morphological structure by means of atomic force microscopy
      (AFM). The method allows measuring directly and describing hydroxyappatite
      crystals on nanolevel. Structural properties of dental hard tissues were
      determined and comparative characteristic of form and density of enamel prisms
      particles with similar morphological inorganic elements of dentin were specified.

PMID- 25377573
TI  - [Glossodynia or burning mouth syndrome: equivalence or difference].
AB  - The term "Burning Mouth Syndrome (BMS)" is being used much more often than
      "Glossodynia", complicating diagnostic and treatment tactic choice. The aim of
      the study was to determine the difference between "Glossodynia" and "BMS"
      considering absence or presence of intraoral metal prosthetic devices and burning
      sensation in the mouth. To establish the frequency of glossodynia and BMS 2355
      patient records were analyzed admitting consultation for oral diseases for the
      last 10 years. Clinically we examined 408 patients aged 40 to 70. The research
      results showed that 17% of patients complained of "burning mouth": 10.2% of them
      had these symptoms due to oral mucosa diseases; 58.0% had glossodynia, 27.4% had
      discomfort because of intolerance to metal prosthodontic materials and 4.4% had
      combined pathology. Glossodynia and intolerance to metal prosthodontic materials
      had much in common in terms of clinical features, but the last one may be
      specified by changes in saliva composition. BMS thus proved to be the common
      definition corresponding to various diseases of oral mucosa and intolerance to
      intraoral metal appliances, while glossoldynia is a distinct neurogenic disease
      which is difficult to treat and requires comprehensive approach involving
      neurologist and physician. 

PMID- 25377574
TI  - [Systemic immunological response in children with chronic gingivitis and gastro
      intestinal pathology].
AB  - Study of the immune system mechanisms in chronic catarrhal gingivitis in children
      with gastrointestinal pathology was performed in 102 children (49 with chronic
      gastritis and duodenitis and 53 with no signs of gastrointestinal pathology).
      Forty-eight children with healthy periodontium constituted control group.
      Generalized chronic catarrhal gingivitis in children with gastroduodenal
      pathology is characterized by intense humoral response by simultaneous T-cell
      immunity suppression. Detection of high serum titers of circulating immune
      complexes in patients with chronic catarrhal gingivitis suggests a role of immune
      response in the pathogenesis of periodontal disease increases with concomitant
      diseases of the upper gastrointestinal tract. 

PMID- 25377575
TI  - [Computer capillaroscopy for periodontal microcirculation assessment in patients
      with early atherosclerotic lesions].
AB  - The study of gingival microvessels was carried out by means of computer
      capillaroscopy in patients with moderate periodontal disease and early symptoms
      of atherosclerosis of extracranial portions of cephalic arteries. The results
      proved the decreased density of the capillar network in the marginal gingiva, as
      well as of linear and volumetric blood flow velocities drop in the arterial and
      venular portions of capillaries in patients with periodontal diseases combined
      with early atherosclerosis. 

PMID- 25377576
TI  - [Structure and specific diagnostic features of neurologic deficiencies in
      patients with maxillofacial injuries admitted to Stavropol Maxillofacial Surgery
      Unit].
AB  - The purpose of the study was to evaluate the structure of maxillofacial trauma
      associated with brain injury in Stavropol to elaborate the diagnostic approach.
      We analyzed 2,604 case records of patients with maxillofacial trauma in the
      Stavropol region in the period from 2008 to 2012. Only 345 (13.2%) cases were
      diagnosed with maxillofacial trauma associated with mild brain injury. The
      analysis of case records showed that the incidence of brain damage depends on the
      location and type of fracture of the facial bones. It is noted that emotional and
      stress factors often mask neurological symptoms that are important in the
      diagnosis of traumatic brain injury. To ensure the treatment success and reduce
      the duration of disability patients with maxillofacial trauma must be provided
      with special treatment with a more thorough analysis of possible neurological
      deficit followed by mandatory therapy for neurological symptoms. 

PMID- 25377577
TI  - [The results of resonance frequency analysis by dental implantation after bone
      augmentation for alveolar bone atrophy].
AB  - The report concerns dental implantation effectiveness in case of jawbone atrophy.
      Thirty patients were included in the study to reveal resonance frequency analysis
      rates of intraosseous dental implants by dental implant placement with bone
      augmentation using the veneer technique of cortico-cancellous blocks and guided
      bone regeneration (GBR) with biodegradable membranes and pins having poly (dl-
      lactic acid) base. 

PMID- 25377578
TI  - [Wound bacterial flora by different methods of second-stage implant surgery].
AB  - Microbiological studies of wound around dental implants disclosed by different
      methods. Significant differences between the methods have not been identified
      that may be important in the choice of tactics of the operation. 

PMID- 25377579
TI  - [Clinical and radiological study on tissue regeneration after alveolar bone
      augmentation with various osteoplastic materials and membranes].
AB  - The aim of the study was to compare the efficiency of alveolar bone augmentation
      using a variety of osteoplastic materials and collagen membrane and healing under
      a clot. The study included patients undergoing the extraction of symmetric teeth.
      After extraction one of the sockets were filled with osteoplastic materials while
      symmetrically located socket with no bone grafting served as a control. In group
      1 augmentation was performed using Bio-Oss Collagen Bio-Gide membrane, in group 2
      - Osteodent-M and Collost membranes, in group 3 - BIOPLAST-dent and BIOPLAST-dent
      MK membranes. Clinical and radiological evaluation revealed positive impact of
      bioplastic materials on the bone tissue healing and recovery rates. The best
      results showed Bio-Oss Collagen with barrier bioresorbable membrane Bio-Gide
      allowing the creation of the most favorable conditions for delayed implantation. 

PMID- 25377580
TI  - [New in conservative therapy of chronic sialoadenitis].
AB  - The use of vasaprostan nucellary form in complex treatment of patients with
      chronic parenchymatous sialoadenitis in a stage of an aggravation in the field of
      amazed salivary gland renders good therapeutic effect, which is proved by
      clinical data and results of reografic and biosemical researches (laktoferrin
      concentration, middlemolecularpeptids and sum of primary and secondary products
      of hyperoxide acidification lipids, basis of Shiff). 

PMID- 25377581
TI  - [Bacteriological monitoring of patients with periimplantitis (preliminary
      study)].
AB  - Studied the microflora properties of pockets around implants of 14 patients at
      the age of 35-68 years old. The research has shown the presence of pathogens, who
      p included into PRC diagnosis. Lhe research also revealed high prevalence of
      obligate piriodontak pathogens in areas of inflammation during periimplantitis.
      with both full and partial adentia. 

PMID- 25377582
TI  - [Indication and technique of human fibrinogen/thrombin-coated collagen patch use
      in mucogingival surgery].
AB  - The aim of the study was to assess the effectiveness of fibrinogen/thrombin
      coated collagen patch by mucogingival operations in patients with somatic
      diseases. Twenty-seven patients aged 25 to 45 (15 males and 12 females) with
      somatic diseases such as arterial hypertension (11 patients), diabetes (8
      patients), bleeding disorders (8 patients) underwent Edlan-Mejcher
      vestibuloplasty. Using fibrinogen/thrombin-coated collagen patch as wound
      dressing caused marked hemostatic effect in 3 to 5 minutes even in hypertension
      and bleeding disorder patients. Wound heeling was observed 14 days post-op with
      no excessive scarring. 

PMID- 25377583
TI  - [Incidence of malocclusion in children living in areas with high fluoride content
      in water].
AB  - The paper presents the results of orthodontic examination of 503 schoolchildren
      from the region with high content of fluoride in drinking water. It was found
      that the prevalence of malocclusions in the examined population subgroup was
      71.38 +/- 2.02%. The highest rate was revealed in the village of Sosnivka 73.69
      +/- 3.20% followed by 69.04 +/- 3.71% and 70.89 +/- 3.61% in the cities of
      Chervonograd and Dobrotvir. Deep bite was diagnosed in 16.70 +/- 1.66% and distal
      occlusion in 13.32 +/- 1.52%. Open bite and mesial occlusion were diagnosed in
      7.35 +/- 1.17% and 4.38 +/- 0.92%. Transversal plane malocclusions were observed
      in 11.53 +/- 1.42%, in 5.37 +/- 1.00% cases the cause was narrow dental arch, in
      2.48 +/- 0.69% - disproportions of the width of the upper and lower dental
      arches. It was revealed that only 3.58 +/- 0.83% of all examined children were
      receiving orthodontic treatment.

PMID- 25377584
TI  - [Improvement of orthodontic treatment outcomes in 6-9 years old children].
AB  - The collaboration between an orthodontist and parents is essential to improve the
      effectiveness of orthodontic treatment of 6-9 years old children. The author
      suggests method for increasing motivation of parents and thus of children by
      using a diary of orthodontic patient as well as modified orthodontic appliance
      with vestibular basis to decrease treatment time. 

PMID- 25377585
TI  - [Efficacy of the caries preventive agents in children during mixed dentition
      period].
AB  - In this blind randomized study the results of the use of agents for dental caries
      prevention are presented. The study included 136 children of 7-12 years old,
      divided into four groups according to the used agent: 3M ESPE Clinpro XT Varnish
      (n=35), Multifluorid (n=37), Gluftored (n=23) and a control group (n=41) who was
      given the recommendations on individual oral hygiene with the use of fluoride
      toothpaste. The groups correlate to gender, age and the risk of dental caries
      development. Prevention efficacy was determined using the test of enamel
      resistance (painting of enamel area pretreated with acid). RESULTS: the use of
      long-acting fluorine varnish 3M ESPE Clinpro XT Varnish statistically
      significantly increases enamel resistance in comparison with other fluorine
      agents. The effect of the agent is due to the possibility of long-term exposure
      to the tooth enamel.

PMID- 25377586
TI  - [Review of legislation base considering requirements for oral hygiene means].
AB  - The paper reviews legislation base considering requirements for oral hygiene
      means in Russian Federation. 

PMID- 25377587
TI  - [Informed consent as an essential condition for dental care providing].
AB  - The paper reviews legislation base considering informed consent as an essential
      condition for dental care providing. 

PMID- 25377588
TI  - The impact of SASA!, a community mobilization intervention, on reported HIV
      related risk behaviours and relationship dynamics in Kampala, Uganda.
AB  - INTRODUCTION: Intimate partner violence (IPV) violates women's human rights, and
      it is a serious public health concern associated with increased HIV risk. SASA!,
      a phased community mobilization intervention, engages communities to prevent IPV
      and promote gender equity. The SASA! study assessed the community-level impact of
      SASA! on reported HIV-related risk behaviours and relationship dynamics. METHODS:
      Data were collected as part of a cluster randomized controlled trial conducted
      between 2007 and 2012 in eight communities in Kampala. An adjusted cluster-level
      intention to treat analysis, compares secondary outcomes in intervention and
      control communities at follow-up. The qualitative evaluation explored
      participants' subjective experience of SASA!. A total of 82 in-depth interviews
      were audio recorded at follow-up, transcribed verbatim and analyzed using
      thematic analysis. RESULTS: Men in intervention communities were significantly
      more likely than controls to report a broad range of HIV-protective behaviours,
      including higher levels of condom use (aRR 2.03, 95% CI 1.22-3.39), HIV testing
      (aRR 1.50, 95% CI 1.13-2.00) and fewer concurrent partners (aRR 0.60, 95% CI 0.37
      0.97). They were also more likely to report increased joint decision-making (aRR
      1.92, 95% CI 1.27-2.91), greater male participation in household tasks (aRR 1.48,
      95% CI 1.09-2.01), more open communication and greater appreciation of their
      partner's work inside (aRR 1.31, 95% CI 1.04-1.66) and outside (aRR 1.49, 95% CI
      1.08-2.06) the home. For women, all outcomes were in the hypothesized direction,
      but effect sizes were smaller. Only some achieved statistical significance. Women
      in intervention communities were significantly more likely to report being able
      to refuse sex with their partners (aRR 1.16, 95% CI 1.00-1.35), joint decision
      making (aRR 1.37, 95% CI 1.06-1.78) and more open communication on a number of
      indicators. Qualitative interviews suggest that shifts operated through broader
      improvements in relationships, including increased trust and cooperation,
      participants' greater awareness of the connections between HIV and IPV and their
      resultant desire to improve their relationships. Barriers to change include
      partial uptake of SASA!, partner resistance, fear and entrenched previous
      beliefs. CONCLUSIONS: SASA! impacted positively on reported HIV-related risk
      behaviours and relationship dynamics at a community level, especially among men.
      Social change programmes focusing on IPV and gender equity could play an
      important role in HIV prevention efforts.

PMID- 25377589
TI  - The effect of elevated carbon dioxide on the interaction between Eucalyptus
      grandis and diverse isolates of Pisolithus sp. is associated with a complex shift
      in the root transcriptome.
AB  - Using the newly available genome for Eucalyptus grandis, we sought to determine
      the genome-wide traits that enable this host to form mutualistic interactions
      with ectomycorrhizal (ECM) Pisolithus sp. and to determine how future predicted
      concentrations of atmospheric carbon dioxide (CO2 ) will affect this
      relationship. We analyzed the physiological and transcriptomic responses of E.
      grandis during colonization by different Pisolithus sp. isolates under conditions
      of ambient (400 ppm) and elevated (650 ppm) CO2 to tease out the gene expression
      profiles associated with colonization status. We demonstrate that E. grandis
      varies in its susceptibility to colonization by different Pisolithus isolates in
      a manner that is not predictable by geographic origin or the internal transcribed
      spacer (ITS)-based phylogeny of the fungal partner. Elevated concentrations of
      CO2 alter the receptivity of E. grandis to Pisolithus, a change that is
      correlated to a dramatic shift in the transcriptomic profile of the root. These
      data provide a starting point for understanding how future environmental change
      may alter the signaling between plants and their ECM partners and is a step
      towards determining the mechanism behind previously observed shifts in Eucalypt
      associated fungal communities exposed to elevated concentrations of atmospheric
      CO2 .

PMID- 25377590
TI  - Chemical assessment state of the science: Evaluation of 32 decision-support tools
      used to screen and prioritize chemicals.
AB  - The last decade has seen an increased focus on evaluating the safety and
      sustainability of chemicals in consumer and industrial products. In order to
      effectively and accurately evaluate safety and sustainability, tools are needed
      to characterize hazard, exposure, and risk pertaining to products and processes.
      Because many of these tools will be used to identify problematic chemistries, and
      because many have potential applications in various steps of an alternatives
      analysis, the limitations and capabilities of available tools should be
      understood by users so that, ultimately, potential chemical risk is accurately
      reflected. In our study, we examined 32 chemical characterization tools from
      government, industry, academia, and non-governmental organizations (NGOs). The
      tools we studied were diverse, and varied widely in their scope and assessment.
      As such, they were separated into five categories for comparison: 1) Screening
      and Prioritization; 2) Database Utilization; 3) Hazard Assessment; 4) Exposure
      and Risk Assessment; and 5) Certification and Labeling. Each tool was scored
      based on our weighted set of criteria, and then compared to other tools in the
      same category. Ten tools received a high score in one or more categories; 24
      tools received a medium score in one or more categories, and five tools received
      a low score in one or more categories. Although some tools were placed into more
      than one category, no tool encompassed all five of the assessment categories.
      Though many of the tools evaluated may be useful for providing guidance for
      hazards - and, in some cases, exposure - few tools characterize risk. To our
      knowledge, this study is the first to critically evaluate a large set of chemical
      assessment tools and provide an understanding of their strengths and limitations.

PMID- 25377592
TI  - A phase I dose-escalation and bioequivalence study of a trastuzumab biosimilar in
      healthy male volunteers.
AB  - BACKGROUND: Trastuzumab (Herceptin((r))) is a humanized monoclonal antibody
      targeting the human epidermal growth factor receptor 2 (HER2) and is used in the
      treatment of HER2-overexpressing breast and gastric cancer. FTMB is being
      developed as a biosimilar of trastuzumab. OBJECTIVE: In this combined dose
      escalation and bioequivalence study of parallel design, the pharmacokinetic
      profile of FTMB was compared with Herceptin((r)). METHODS: Healthy male
      volunteers received single doses of 0.5, 1.5, 3.0 or 6.0 mg/kg FTMB, or placebo,
      in consecutive dose-escalation cohorts to assess the safety profile. Thereafter,
      the 6 mg/kg cohort was expanded to establish bioequivalence between FTMB (Test)
      and Herceptin((r)) (Reference) based on an acceptance interval of 80.0-125.0 %.
      In total, 118 subjects were enrolled in the study. RESULT: The mean area under
      the concentration-time curve from time zero to infinity (AUCinfinity) was 1,609
      ug.day/mL (Test) and 1,330 ug.day/mL (Reference). The log-transformed geometric
      mean Test/Reference (T/R) ratio for AUCinfinity was 89.6 % (90 % confidence
      interval [CI] 85.1-94.4), demonstrating bioequivalence. For the secondary
      endpoint, the maximum concentration observed (Cmax), the geometric mean T/R ratio
      was 89.4 % (90 % CI 83.4-95.9). Non-linear, target-mediated pharmacokinetics were
      also observed. Adverse events other than the documented side effects of
      Herceptin((r)) (fever, influenza-like illness, and fatigue) did not occur. No
      signs of cardiotoxicity were observed. CONCLUSIONS: This bioequivalence study
      with a trastuzumab biosimilar in healthy male volunteers demonstrated
      bioequivalence of FTMB with Herceptin((r)). FTMB was well tolerated in doses up
      to 6 mg/kg. Non-linear target elimination was also observed in the
      pharmacokinetic profile of trastuzumab.

PMID- 25377591
TI  - Dried plasma/blood spots for monitoring antiretroviral treatment efficacy and
      pharmacokinetics: a cross-sectional study in rural Burundi.
AB  - AIMS: In limited resource settings monitoring antiretroviral (ARV) treatment
      efficacy is restrained by the lack of access to technological equipment. The aim
      of the study was to assess the use of dried plasma (DPS) and blood spots (DBS) to
      facilitate ARV monitoring in remote settings where clinical monitoring is the
      primary strategy. METHODS: A cross-sectional study in HIV-positive ARV-treated
      patients in Kiremba, Burundi was performed. DBS were used for HIV-1 viral load
      (limit of the assay 250 copies ml(-1)) and genotypic drug resistance tests and
      dried plasma spots were used for concentration measurements. RESULTS: Three
      hundred and seven patients [201 female (88.6%), 14 children (4.5%)] were
      enrolled. HIV-1 viral load was <250, 250-1000 and >1000 copies ml(-1) in 250
      (81.7%), 33 (10.8%) and 23 patients (7.5%). Eleven samples out of 23 were
      successfully amplified revealing nucleoside reverse transcriptase inhibitor
      (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistance
      associated mutations [in seven (58.3%) and six patients (50%)]. Nevirapine trough
      concentrations were <3000 ng ml(-1) in 28/189 patients (14.8%) and efavirenz 12 h
      concentrations were <1000 ng ml(-1) in 2/16 patients (12.5%). Children and
      patients with nevirapine exposure <3000 ng ml(-1) presented a higher risk of
      viral replication. CONCLUSIONS: Viral loads <250 copies ml(-1) were observed in
      81.7% of patients (83.6% adults and 42.9% children). Children and patients with
      low nevirapine concentrations had higher risk of viral replication. Dried blood
      and plasma spots may be useful for monitoring HIV-positive patients including
      viral load and drug level measurement as part of treatment management in remote
      areas.

PMID- 25377593
TI  - Experiencing reproductive concerns as a female cancer survivor is associated with
      depression.
AB  - BACKGROUND: Young adult female cancer survivors have unmet reproductive concerns
      and informational needs that are associated with poorer quality of life. The
      purpose of this study was to examine the association between current reproductive
      concerns and moderate to severe depression among young survivors. METHODS: This
      cross-sectional study included 200 female cancer survivors between the ages of 18
      and 35 years who completed a Web-based survey measuring reproductive history,
      parenthood desires, reproductive concerns after cancer, and quality-of-life
      indicators. RESULTS: The mean age of the participants was 28 years (standard
      deviation, 4.4 years), and almost two-thirds were diagnosed within 5 years of
      survey completion. A multivariate logistic regression analysis controlling for
      education, duration of survivorship, and social support revealed an association
      between experiencing reproductive concerns and moderate to severe depression
      (odds ratio for each 5-unit increase in the Reproductive Concerns After Cancer
      [RCAC] score, 1.30; 95% confidence interval, 1.06-1.60). Among those with
      moderate to severe depression, 23% had high RCAC scores, whereas 6% of those with
      minimal to mild depression did (P < .001). CONCLUSIONS: A higher level of
      reproductive concerns was associated with greater odds of experiencing moderate
      to severe depression. Almost a quarter of survivors in this sample reported
      moderate to severe depression, and addressing reproductive concerns represents
      one potential area of intervention for improving the psychosocial health of young
      survivors.

PMID- 25377595
TI  - Settling the "dead layer" debate in nanoscale capacitors.
AB  - Permittivity peaks in single crystal thin film capacitors are strongly suppressed
      compared to bulk in the case of Pt/SrTiO3 /Pt, but are relatively unaffected in
      Pt/BaTiO3 /Pt structures. This is consistent with the recent suggestion that
      subtle variations in interfacial bonding between the dielectric and electrode are
      critical in determining the presence or absence of inherent dielectric "dead
      layers". 

PMID- 25377596
TI  - A simple method for the investigation of cell separation effects of blood with
      physiological hematocrit values.
AB  - Even though the separation of blood into erythrocyte-rich and erythrocyte-poor
      areas is well known in physiological setups such as small vessels, it has
      recently come into focus in small gaps in cardiovascular applications. Studies
      show that separation effects occur, for example, in gaps in hydrodynamic
      bearings, where they can have a positive effect on hemolysis. Separation effects
      depend on the hematocrit value, but due to visualization issues, studies in small
      gaps used very low hematocrit values. In this study, a test setup and an
      evaluation method for the investigation of separation effects of blood with
      hematocrit values of 30, 45, and 60% were developed. The erythrocyte distribution
      was evaluated by means of gray scale value distribution. This principle is based
      on the fact that an erythrocyte-rich region is more opaque than an erythrocyte
      poor region. The experimental setup is designed in a way that no further
      processes (e.g., fluorescence labeling) need to be carried out which might change
      the properties of the membrane of the erythrocytes, and therefore their flow
      properties. Additionally, the method is executable with basic laboratory
      equipment, which makes it applicable for many laboratories. To validate the
      feasibility of the method, the influence of the diameter and the flow rate on the
      migration of erythrocytes were studied in micro channels for three different
      physiological hematocrit values. Even though no individual cells were traced,
      plasma layer and areas of high erythrocyte concentration could be identified.
      Dependencies of the erythrocyte distribution on flow rate and channel diameter
      were validated. The influence of the hematocrit value was demonstrated as well
      and showed the hematocrit value to be a crucial factor when investigating cell
      separation. The experimental results were consistent with findings in the
      literature. As the developed method is suitable for physiological hematocrit
      values and easy to handle, it provides an optimal basis for cell separation
      studies in gap models with whole blood, for example, hydrodynamic bearings, where
      it can be used to optimize these devices. 

PMID- 25377597
TI  - Impact of cell arrangement of pleural effusion in survival of patients with
      breast cancer.
AB  - OBJECTIVE: This study was performed to evaluate the potential influence of
      cytological differences between pleural effusions on the survival of women with
      metastatic breast cancer during 30 months of follow-up. STUDY DESIGN: A hospital
      based cohort study was performed. Pleural fluid cytology slides from patients
      with breast cancer were examined. Cases were grouped according to the pattern of
      tumor cells (spheroid and isolated), in order to access their prognostic value.
      RESULTS: The study comprised 87 patients. An isolated cell pattern was associated
      with higher mortality 30 months after the pleural effusion when compared to a
      spheroid pattern (p = 0.038). Patients with an isolated cell pattern showed
      higher risk of dying than patients with spheroid formations. The relative risk
      after adjustment of intervening variables was 5.336 (95% CI 1.054-27.020). The
      presence of a triple-negative immunohistochemical pattern significantly increased
      the risk of mortality before 30 months. CONCLUSION: Pleural effusion with
      isolated malignant cells is associated with worse prognosis after 30 months of
      follow-up.

PMID- 25377594
TI  - Plasmonic biosensors.
AB  - The unique optical properties of plasmon resonant nanostructures enable
      exploration of nanoscale environments using relatively simple optical
      characterization techniques. For this reason, the field of plasmonics continues
      to garner the attention of the biosensing community. Biosensors based on
      propagating surface plasmon resonances (SPRs) in films are the most well
      recognized plasmonic biosensors, but there is great potential for the new,
      developing technologies to surpass the robustness and popularity of film-based
      SPR sensing. This review surveys the current plasmonic biosensor landscape with
      emphasis on the basic operating principles of each plasmonic sensing technique
      and the practical considerations when developing a sensing platform with the
      various techniques. The 'gold standard' film SPR technique is reviewed briefly,
      but special emphasis is devoted to the up-and-coming localized surface plasmon
      resonance and plasmonically coupled sensor technology.

PMID- 25377598
TI  - Electric tuning of direct-indirect optical transitions in silicon.
AB  - Electronic band structures in semiconductors are uniquely determined by the
      constituent elements of the lattice. For example, bulk silicon has an indirect
      bandgap and it prohibits efficient light emission. Here we report the electrical
      tuning of the direct/indirect band optical transition in an ultrathin silicon-on
      insulator (SOI) gated metal-oxide-semiconductor (MOS) light-emitting diode. A
      special Si/SiO2 interface formed by high-temperature annealing that shows
      stronger valley coupling enables us to observe phononless direct optical
      transition. Furthermore, by controlling the gate field, its strength can be
      electrically tuned to 16 times that of the indirect transition, which is nearly
      800 times larger than the weak direct transition in bulk silicon. These results
      will therefore assist the development of both complementary MOS (CMOS)-compatible
      silicon photonics and the emerging "valleytronics" based on the control of the
      valley degree of freedom. 

PMID- 25377599
TI  - The impact of metformin treatment on adiponectin and resistin levels in women
      with polycystic ovary syndrome: a prospective clinical study.
AB  - Women with polycystic ovary syndrome (PCOS) are often characterized by adiposity
      and insulin resistance (IR). Recent studies in patients with obesity and diabetes
      mellitus type 2 (DMt2) indicate that adiponectin and resistin may play a role in
      the pathophysiology of IR. The aim of this study was to identify a possible
      correlation between the plasma levels of adiponectin and resistin and IR in
      patients with PCOS. Thirty-one women of reproductive age were enrolled in this
      prospective study after being diagnosed with PCOS and IR according to Rotterdam
      and American Diabetes Association (ADA) criteria, respectively. Every patient was
      treated with a daily dose of 1275 mg metformin for 6 months. Adiponectin,
      resistin, and the primary hormonal and metabolic parameters of the syndrome were
      evaluated at entry and endpoint of treatment. Adiponectin plasma levels were
      reduced after metformin treatment, but resistin levels were not significantly
      affected. Our study suggests that circulating levels of adiponectin should be
      evaluated with skepticism in patients with PCOS. The adipokine's role in the
      manifestation of IR in PCOS remains unclear and needs further investigation.

PMID- 25377600
TI  - Clinical and molecular characteristics of invasive community-acquired
      Staphylococcus aureus infections in Chinese children.
AB  - BACKGROUND: This study aims to investigate the clinical features of invasive
      community-acquired Staphylococcus aureus (CA-SA) infection in Chinese children
      and analyze its molecular features. METHODS: Clinical data and invasive CA-SA
      isolates were prospectively collected. Pediatric risk of mortality (PRISM) score
      was used for disease severity measurement. Molecular typing was then performed,
      followed by expression analysis for virulence genes. RESULTS: Among 163 invasive
      CA-SA infection cases, 71 (43.6%) were methicillin-resistant SA (MRSA) infections
      and 92 (56.4%) were methicillin-susceptible SA (MSSA). A total of 105 (64.4%)
      children were younger than 1 year old, and 79.7% (129/163) were under 3 years
      age. Thirteen kinds of diseases were observed, in which bacteremia and pneumonia
      accounted for 65.6% (107/163) and 52.8% (86/163), respectively. A total of 112
      (68.1%) patients had two or more infective sites simultaneously, and four cases
      (2.5%) died. CA-MSSA more frequently caused multi-sites infections, bacteremia,
      and musculoskeletal infection than MRSA. A total of 25 sequence types (STs) were
      detected. MRSA mainly comprised ST59 (49/71, 69%), whereas the most frequent
      clonotypes were ST88 (15/92, 16.3%), ST25 (13/92, 14.1%), ST7 (13/92, 14.1%),
      ST2155 (12/92, 13%), and ST188 (9/92, 9.8%) for MSSA. Seven STs were common to
      both MSSA and MRSA groups. No differences in clinical presentation or PRISM score
      were found between the two groups or among different ST. The expression levels of
      the four known virulence genes varied among the six main ST clones. CONCLUSIONS:
      Invasive CA-SA infections were characterized by high incidence and multi-site
      infections in young children in China. The clinical manifestations of CA-MSSA
      were more frequently associated with multi-site infections, bacteremia and
      musculoskeletal infection than those of CA-MRSA. Isolated genotypes may be
      relevant to the expressions of virulence genes, but not to clinical
      manifestations.

PMID- 25377601
TI  - Impact of gender on the decision to participate in a clinical trial: a cross
      sectional study.
AB  - BACKGROUND: In order for Informed Consent to be ethical and valid each clinical
      trial participant must be able to make a voluntary decision to participate, free
      from pressure or coercion. Nonetheless, many factors may influence the decision
      reached, and such influences may be different for male and female volunteers.
      Being aware of these differences may help researches develop better processes for
      obtaining consent that safeguard the right of autonomy for all participants. The
      goal of this study was to evaluate potential gender-based differences in the
      factors influencing clinical trial participation. METHODS: This cross-sectional
      study was conducted in the Northeast region of Minas Gerais, Brazil, in October
      2011. A structured questionnaire was administered to 143 volunteers (48 male, 95
      female) screened for participation in a clinical study of an investigational
      functional food with potential anthelminthic properties. Answers regarding their
      decision to participate in the study were compared, by gender, using chi-square
      and Mann Whitney tests. Odds ratios (OR) was used to measure association.
      RESULTS: A majority of subjects (58% of males, 59% of females) listed the desire
      to collaborate with the development of a product against parasitic worms as their
      main reason for participation. Females were significantly more likely to report a
      decision influenced by friends, family, or researchers (OR 3.14, 3.45, and 3.46
      respectively, p < 0.005). Females were also significantly more likely to report a
      decision influenced by general altruistic considerations (OR 8.45, p < 0.005).
      There was no difference, by gender, in the report of decisions influenced by
      informational meetings, understanding of the disease, or the availability of
      medical treatments or exams. There was also no difference in knowledge of the
      rights of research participants. CONCLUSION: Study results indicate that there is
      a strong difference between male and female participants regarding social
      influences on the decision to participate in clinical research. Further research
      into the impact this may have on autonomy is warranted.

PMID- 25377602
TI  - Emerging topics in bipolar disorder. Introduction.

PMID- 25377603
TI  - Restoring functioning in bipolar disorder: functional remediation.
AB  - Over the past several years, many evidence-based interventions have proven to be
      effective as adjunctive therapies in the treatment of bipolar disorder. Only a
      few, however, have addressed the issue of functional recovery in bipolar euthymic
      patients, which is difficult to achieve after an affective episode. The
      functional remediation program has been designed at the Hospital Clinic of
      Barcelona with the main aim of treating functional impairment in bipolar
      disorder. The program consists of 21 weekly group sessions and is based on a
      neuro-cognitive-behavioral approach. Throughout the sessions, euthymic patients
      are trained in the use of neurocognitive skills to be applied during their daily
      routines. Modeling techniques, role playing, self-instructions, verbal
      instructions, positive reinforcement, and metacognitive cues are some of the
      techniques that are used in the program. The present report aims at explaining
      this new intervention to improve functional outcomes in euthymic bipolar
      patients.

PMID- 25377604
TI  - The effects of HPA axis function on cognition and its implications for the
      pathophysiology of bipolar disorder.
AB  - Bipolar disorders (BDs) are common and complex diseases. Recent findings have
      provided the basis for an integrated approach linking seemingly disparate
      findings, based on a greater understanding of the effects of stress on those
      vulnerable to these illnesses and the brain's consequent responses. Genes are
      associated with this disorder, although their integration into current
      pathophysiological models is unclear. Manic states are associated with enhanced
      dopaminergic transmission, and experimental stress enhances dopamine
      neurotransmission and impairs cognition. Stress activates the hypothalamic
      pituitary-adrenal axis, and dysfunction of this axis and impairments in
      neurocognitive function have both been demonstrated in BD. Glucocorticoid
      receptors are abnormal in postmortem brain studies in BD and play an important
      role in the HPA axis. The glucocorticoid receptor antagonist RU-486 has been
      shown to improve aspects of cognitive function in BD. The implications of these
      findings for models of pathophysiology are discussed. Future efforts should focus
      on further integrating the current and emerging research findings into a coherent
      pathophysiological model that generates testable hypotheses. 

PMID- 25377606
TI  - Recent findings on the role of white matter pathology in bipolar disorder.
AB  - Patients with bipolar disorder (BD) experience difficulties in information
      processing and in the cognitive control of emotions. Mood-congruent biases, which
      parallel illness episodes, find a neural correlate in abnormal reactivity to
      stimuli in specific brain regions, and in disrupted functional connectivity among
      brain areas pertaining to corticolimbic circuitries. It is suggested that a
      reduced integrity of white matter tracts could underpin dysfunctions in networks
      implicated in the generation and control of affect. Recent studies using
      diffusion tensor imaging techniques found that (1) independent of drug treatment,
      patients with BD show widespread signs of disrupted white matter microstructure,
      suggesting significant demyelination/dysmyelination without axonal loss, and (2)
      effective long-term treatment with lithium is associated with increased axial
      connectivity, proportional to the duration of treatment. These findings suggest
      that changes of white matter microstructure in specific brain networks could
      parallel disrupted neural connectivity during illness episodes in BD and that
      these changes might play a major role in the mechanistic explanation of the
      biological underpinnings of BD psychopathology. 

PMID- 25377605
TI  - Glial abnormalities in mood disorders.
AB  - Multiple lines of evidence indicate that mood disorders are associated with
      abnormalities in the brain's cellular composition, especially in glial cells.
      Considered inert support cells in the past, glial cells are now known to be
      important for brain function. Treatments for mood disorders enhance glial cell
      proliferation, and experimental stimulation of cell growth has antidepressant
      effects in animal models of mood disorders. These findings suggest that the
      proliferation and survival of glial cells may be important in the pathogenesis of
      mood disorders and may be possible targets for the development of new treatments.
      In this article we review the evidence for glial abnormalities in mood disorders,
      and we discuss glial cell biology and evidence from postmortem studies of mood
      disorders. The goal is not to carry out a comprehensive review but to selectively
      discuss existing evidence in support of an argument for the role of glial cells
      in mood disorders. 

PMID- 25377607
TI  - Neurocognitive correlates of the course of bipolar disorder.
AB  - Significant cognitive dysfunction has been recognized as an important state and
      trait feature of bipolar disorder. In this article, longitudinal studies
      comparing cognitive performance in bipolar disorder patients and healthy controls
      are reviewed. In contrast to cross-sectional reports, current longitudinal
      research findings do not support a progressive cognitive decline over time.
      However, a higher within-person instability in cognitive performance was found
      relative to controls. The need for larger samples remains, as well as for longer
      and more frequent observations. 

PMID- 25377608
TI  - New ways of modeling bipolar disorder.
AB  - There is a well-known deficiency in valid animal models for bipolar disorder.
      Developing the single ideal model for the disorder-one that will represent its
      full scope-will probably not be possible until we have a much better
      understanding of the underlying pathology. Yet, intermediate models, even with
      partial validity, are critical in order to advance our knowledge and put us into
      position to develop even better models. The present article discusses the various
      efforts under way to develop the best models based on our current level of
      understanding. These efforts include (1) identifying new tests, (2) developing
      models based on the endophenotypes approach, (3) identifying the best rodent
      strains, (4) identifying the most appropriate species, (5) segregating
      susceptible versus resilient animals, and (6) segregating animals that respond or
      do not respond to treatment. It is suggested that a combined approach that
      includes these directions and others can result in better models with higher
      validity that will offer significant help in advancing research on bipolar
      disorder and developing new and better treatments. 

PMID- 25377609
TI  - Factors associated with lithium efficacy in bipolar disorder.
AB  - About one-third of lithium-treated, bipolar patients are excellent lithium
      responders; that is, lithium monotherapy totally prevents further episodes of
      bipolar disorder for ten years and more. These patients are clinically
      characterized by an episodic clinical course with complete remission, a bipolar
      family history, low psychiatric comorbidity, mania-depression episode sequences,
      a moderate number of episodes, and a low number of hospitalizations in the pre
      lithium period. Recently, it has been found that temperamental features of
      hypomania (a hyperthymic temperament) and a lack of cognitive disorganization
      predict the best results of lithium prophylaxis. Lithium exerts a neuroprotective
      effect, in which increased expression of brain-derived neurotrophic factor (BDNF)
      and inhibition of the glycogen synthase kinase-3 (GSK-3) play an important role.
      The response to lithium has been connected with the genotype of the BDNF gene and
      serum BDNF levels. A better response to lithium is connected with the Met allele
      of the BDNF Val/Met polymorphism, as is a hyperthymic temperament. Excellent
      lithium responders have normal cognitive functions and serum BDNF levels, even
      after long-term duration of the illness. The preservation of cognitive functions
      in long-term lithium-treated patients may be connected with the stimulation of
      the BDNF system, with the resulting prevention of affective episodes exerting
      deleterious cognitive effects, and possibly also with lithium's antiviral
      effects. A number of candidate genes that are related to neurotransmitters,
      intracellular signaling, neuroprotection, circadian rhythms, and other pathogenic
      mechanisms of bipolar disorder were found to be associated with the lithium
      prophylactic response. The Consortium on Lithium Genetics (ConLiGen) has recently
      performed the first genome-wide association study on the lithium response in
      bipolar disorder.

PMID- 25377610
TI  - Stimulants for treating bipolar disorder: pro and con.
AB  - The role of stimulants for treating severe depression remains controversial,
      especially when it comes to bipolar depression. Potential benefits have to be
      weighed against risks, including addictive potential and treatment-emergent
      mania. But not all stimulants are the same. Modafinil and its R-enantiomer
      armodafinil seem to have positive augmentation effects when coupled with standard
      treatment of bipolar depression, while also having a relative low risk of
      addiction and manic switches. A recent hypothesis derived from the observation of
      hypovigilance in manic patients postulates that modafinil may also have a
      beneficial effect in reducing manic behaviors. Further controlled studies are
      needed to clarify the benefits and risks of stimulants, both in bipolar
      depression and mania. 

PMID- 25377611
TI  - Role of adverse effects in medication nonadherence in bipolar disorder.
AB  - Nonadherence to medications is common and associated with poor or limited
      clinical outcomes in the treatment of bipolar disorder. A review of the
      literature discloses that adverse effects are one of the commonly reported
      reasons for nonadherence to mood stabilizers by patients with bipolar disorder.
      Nevertheless, other than such broad summaries, relatively little attention has
      been given to the role of adverse effects in relation to nonadherence. This
      review article is the first to consolidate the available data on this topic.
      Weight gain, perceived cognitive impairment, tremors, and sedation are the
      adverse effects most likely to lead to nonadherence. Further research is needed
      to anticipate, identify, manage, and potentially minimize the impact of adverse
      effects. 

PMID- 25377612
TI  - Critical issues on the use of network meta-analysis in psychiatry.
AB  - The need to support clinical decision making and cost-effectiveness analyses in
      medicine, despite a dearth of head-to-head treatment comparisons, has encouraged
      the development of methods enabling indirect comparisons of treatment
      alternatives, including network meta-analysis (NMA). Valid application of NMA
      requires close similarity of compared trials, including their design, patient
      characteristics, and methods of diagnosis and symptomatic assessment. When
      biological or other objective measures of outcomes are not available, as is the
      case in psychiatric disorders, subtle differences in characteristics of trials or
      participants may lead to unrecognized incoherence within a network and thus to
      inconsistent results. By considering comparative-efficacy analyses of
      psychotropic drugs in major psychiatric disorders as working examples, we
      underscore the risks of violating the fundamental transitivity assumption in the
      context of NMA and suggest precautions for creating a coherent network. We
      conclude that with thoughtful and critical application, NMA can add useful
      information concerning the comparative benefits, risks, and costs of specific
      treatments in psychiatry. 

PMID- 25377613
TI  - Unexplored areas of psychotherapy in bipolar disorder.
AB  - Several psychological interventions-including group psychoeducation, family
      focused psychoeducation, and interpersonal social-rhythm therapy-have
      demonstrated prophylactic efficacy as an adjunct to medication in bipolar
      disorders (BDs). The field of psychological interventions for BD has experienced
      impressive progress over the last 15 years. Certain unexplored areas, however,
      require further research in order to establish the full potential of
      psychological interventions for BD. Such research should focus, among other
      things, on cognitive impairment associated with BD, BD in the elderly, comorbid
      anxiety disorders and other comorbidities, the treatment of BD in pregnant women,
      and the improvement of patients' overall physical health. 

PMID- 25377614
TI  - Is antiepileptic-induced suicidality a data-based class effect or an
      exaggeration? A comment on the literature.
AB  - A few years ago the Food and Drug Administration, based on a meta-analysis,
      issued a warning stating that antiepileptic drugs (AEDs) are associated with an
      increased risk of suicidal ideation, suicide attempts, and completed suicide.
      This warning generated significant concern about the use of AEDs, especially in
      patients with epilepsy and affective disorders. Following the FDA report, several
      studies addressed this issue but only served to generate further concern and
      confusion. There seems to be no convincing data concerning a "class effect" of
      AEDs in inducing any type of suicide-related behaviors. Some data suggest a
      possible association of lamotrigine, levetiracetam, and topiramate with
      suicidality, but further research is needed. In any case, clinicians need to
      carefully assess suicidality in all patients treated with AEDs and inform them
      and their families on the possible increased risk of suicidality, though
      preferably in a way that keeps open the continuing use of AEDs. 

PMID- 25377618
TI  - Hearing preservation after lateral temporal bone resection for early-stage
      external auditory canal carcinoma.
AB  - OBJECTIVE: To evaluate postoperative hearing outcomes after lateral temporal bone
      resection (LTBR) with reconstruction of the external auditory canal (EAC) and
      conductive function for early-stage EAC carcinoma. METHODS: We retrospectively
      examined patients diagnosed with early-stage EAC carcinoma treated with surgery
      alone between January 2006 and December 2012. Patients who had postoperative
      adjuvant chemotherapy and/or radiotherapy were excluded. Patients receiving LTBR
      in combination with tympanoplasty were divided into two groups based on the
      reconstruction of the EAC with and without (w/o) split-thickness skin grafts
      (STSGs). Audiological data included the preoperative hearing thresholds and the
      most recent postoperative hearing thresholds obtained at least 12 months after
      surgery. The hearing outcome was evaluated based on pure-tone audiograms using
      the Committee on Hearing and Equilibrium guidelines of the American Academy of
      Otolaryngology-Head and Neck Surgery for the evaluation of the results of
      treatment of conductive hearing loss. The postoperative quality of life (QOL) for
      patients was evaluated using the Glasgow Benefit Inventory (GBI). RESULTS: All
      patients (n = 15) achieved disease-free survival without significant morbidity or
      mortality. When we compared the mean air-bone gaps after surgery, those in the
      STSG group (n = 8) were found to be significantly lower than those in the w/o
      STSG group (n = 7; p < 0.001). The success rate for postoperative hearing was
      75.0% in the STSG group, which was significantly higher than that in the w/o STSG
      group (p = 0.014). All patients in the w/o STSG group showed stenosis and closure
      of the EAC at fewer than 10 months after surgery. In contrast, all patients in
      the STSG group showed preserved conformation of the new EAC for more than 12
      months after surgery. When we compared the mean GBI score between the two groups
      of patients, the overall and general health scores in the STSG group were found
      to be significantly higher than those in the w/o STSG group (p = 0.021, p =
      0.001). CONCLUSIONS: Reconstruction of the EAC using a rolled-up STSG technique
      in combination with tympanoplasty after LTBR is useful for hearing preservation
      and the observation of locoregional lesions after surgery, resulting in improved
      QOL for patients.

PMID- 25377619
TI  - Forest filter effect versus cold trapping effect on the altitudinal distribution
      of PCBs: a case study of Mt. Gongga, eastern Tibetan Plateau.
AB  - Mountains are observed to preferentially accumulate persistent organic pollutants
      (POPs) at higher altitude due to the cold condensation effect. Forest soils
      characterized by high organic carbon are important for terrestrial storage of
      POPs. To investigate the dominant factor controlling the altitudinal distribution
      of POPs in mountainous areas, we measured concentrations of polychlorinated
      biphenyls (PCBs) in different environmental matrices (soil, moss, and air) from
      nine elevations on the eastern slope of Mt. Gongga, the highest mountain in
      Sichuan Province on the Tibetan Plateau. The concentrations of 24 measured PCBs
      ranged from 41 to 510 pg/g dry weight (dw) (mean: 260 pg/g dw) in the O-horizon
      soil, 280 to 1200 pg/g dw (mean: 740 pg/g dw) in moss, and 33 to 60 pg/m(3)
      (mean: 47 pg/m(3)) in air. Soil organic carbon was a key determinant explaining
      75% of the variation in concentration along the altitudinal gradient. Across all
      of the sampling sites, the average contribution of the forest filter effect (FFE)
      was greater than that of the mountain cold trapping effect based on principal
      components analysis and multiple linear regression. Our results deviate from the
      thermodynamic theory involving cold condensation at high altitudes of mountain
      areas and highlight the importance of the FFE. 

PMID- 25377621
TI  - Flow-driven triboelectric generator for directly powering a wireless sensor node.
AB  - A triboelectric generator (TEG) for scavenging flow-driven mechanical -energy to
      directly power a wireless sensor node is demonstrated for the first time. The
      output performances of TEGs with different dimensions are systematically
      investigated, indicating that a largest output power of about 3.7 mW for one TEG
      can be achieved under an external load of 3 MOmega.

PMID- 25377620
TI  - Therapeutic action of 5-HT3 receptor antagonists targeting peritoneal macrophages
      in post-operative ileus.
AB  - BACKGROUND AND PURPOSE: Post-operative ileus (POI) is induced by intestinal
      inflammation. Here, we aimed to clarify the effects of 5-HT3 receptor antagonists
      against POI. EXPERIMENTAL APPROACH: We administered three 5-HT3 receptor
      antagonists, ondansetron, tropisetron and palonosetron, to a mouse model of POI
      induced by surgical intestinal manipulation (IM). Immunohistochemistry,
      intestinal transit, inflammatory mediator mRNA expression and 5-HT content were
      measured. In some experiments, 5-HT3 A receptor null mice were used. KEY RESULTS:
      Three 5-HT3 receptor antagonists reduced IM-induced infiltration of inflammatory
      CD68-positive macrophages and myeloperoxidase-stained neutrophils. Ondansetron
      exhibited no anti-inflammatory actions in 5-HT3 A receptor null mice. Ondansetron
      inhibited expression of the chemokine CCL2, IL-1beta, IL-6, TNF-alpha and iNOS
      mRNAs up-regulated by IM, and also ameliorated the delayed gastrointestinal
      transit. Peritoneal macrophages, but not most infiltrating monocyte-derived
      macrophages, expressed 5-HT3 receptors. IM stimulation increased the 5-HT content
      of peritoneal lavage fluid, which up-regulated mRNA expression of proinflammatory
      cytokines in peritoneal macrophages. Immunohistochemical localization of 5-HT3
      receptors suggests that ondansetron suppressed expression of these mRNAs in
      activated peritoneal macrophages, adhering to the serosal region of the inflamed
      intestinal wall. CONCLUSION AND IMPLICATIONS: 5-HT3 receptor antagonists were
      anti-inflammatory, mainly targeting peritoneal macrophages expressing these
      receptors. They also restored the delayed gastrointestinal transit by IM. 5-HT3
      receptor antagonists should be therapeutically useful agents against POI.

PMID- 25377622
TI  - Temperament-based treatment for anorexia nervosa.
AB  - Anorexia nervosa (AN) tends to be a chronic and deadly disorder with no proven
      treatments that reverse core symptoms in adults. New insight into neurobiological
      mechanisms that contribute to symptoms may support development of more effective
      interventions. We describe the development of a temperament-based treatment for
      AN on the basis of empirically supported models. It uses a systemized approach
      and takes into consideration an understanding of how neurobiological mechanisms
      are expressed through behaviour and personality and contribute to specific AN
      symptomatology. This model integrates the development of AN-focused constructive
      coping strategies with carer-focused strategies to manage temperament traits that
      contribute to AN symptomatology. This intervention is consistent with the recent
      Novel Interventions for Mental Disorders initiative mandating that treatment
      trials follow an experimental medicine approach by identifying underlying
      mechanisms that are directly targeted by the intervention to influence symptoms.

PMID- 25377623
TI  - Systematic identification of the lysine succinylation in the protozoan parasite
      Toxoplasma gondii.
AB  - Lysine succinylation is a new posttranslational modification identified in
      histone proteins of Toxoplasma gondii, an obligate intracellular parasite of the
      phylum Apicomplexa. However, very little is known about their scope and cellular
      distribution. Here, using LC-MS/MS to identify parasite peptides enriched by
      immunopurification with succinyl lysine antibody, we produced the first lysine
      succinylome in this parasite. Overall, a total of 425 lysine succinylation sites
      that occurred on 147 succinylated proteins were identified in extracellular
      Toxoplasma tachyzoites, which is a proliferative stage that results in acute
      toxoplasmosis. With the bioinformatics analysis, it is shown that these
      succinylated proteins are evolutionarily conserved and involved in a wide variety
      of cellular functions such as metabolism and epigenetic gene regulation and
      exhibit diverse subcellular localizations. Moreover, we defined five types of
      definitively conserved succinylation site motifs, and the results imply that
      lysine residue of a polypeptide with lysine on the +3 position and without lysine
      at the -1 to +2 position is a preferred substrate of lysine succinyltransferase.
      In conclusion, our findings suggest that lysine succinylation in Toxoplasma
      involves a diverse array of cellular functions, although the succinylation occurs
      at a low level. 

PMID- 25377624
TI  - Synergistic steric effects in the development of a palladium-catalyzed alkyne
      carbohalogenation: stereodivergent synthesis of vinyl halides.
AB  - We report our finding that by exploiting the synergistic steric effects between
      substrate and catalyst, an intramolecular Pd-catalyzed alkyne carbohalogenation
      can be achieved. This operationally simple method uses the bulky Pd/Q-Phos
      combination and allows access to tetrasubstituted vinyl halides from the
      corresponding aryl chlorides, bromides, and iodides. Steric effects in the
      substrate play a key role by promoting C sp 2-halogen reductive elimination and
      enabling catalytic turnover. Through a reversible oxidative addition mechanism, a
      thermodynamically driven isomerization reaction is observed at elevated
      temperatures. Thus by changing the reaction temperature, both stereoisomers of
      the reaction become readily accessible. 

PMID- 25377625
TI  - Comparative anatomy of the pelvic vessels in the bearded capuchin (Sapajus
      libidinosus) and baboons, apes and modern humans.
AB  - Cebus/Sapajus has shown high cognitive and manipulatory behaviour as well as
      intermittent bipedalism. Although the function of the muscles and bones of this
      genus has been widely investigated, the arterial system that supports these
      tissues has not been studied in much detail, and a full description of the blood
      vessels of the pelvis is still missing. Therefore, we studied the vessels of the
      pelvis of Sapajus libidinosus in terms of their origin, distribution and muscle
      irrigation and compared them with those of other primates available in the
      literature. In general, the distribution pattern and origin of arteries in the
      pelvis of the bearded capuchin are more similar to those of baboons compared to
      other primates. This similarity may be because both have a tail, a similar body
      shape and use, preferentially, quadrupedal movement.

PMID- 25377626
TI  - Greater loss of white matter integrity in postural instability and gait
      difficulty subtype of Parkinson's disease.
AB  - BACKGROUND: Patients with the postural instability and gait difficulty (PIGD)
      subtype of Parkinson disease (PD) are at a higher risk of dysfunction and are
      less responsive to dopamine replacement therapy. The PIGD subtype was found to
      largely associate with white matter lesions, but details of the diffusion changes
      within these lesions have not been fully investigated. Voxel-based analysis for
      diffusion tensor imaging data is one of the preferred measures to compare
      diffusion changes in each voxel in any part of the brain. METHODS: PD patients
      with the PIGD (n=12) and non-PIGD subtypes (n=12) were recruited to compare
      diffusion differences in fractional anisotropy, axial diffusivity, and radial
      diffusivity with voxel-based analysis. RESULTS: Significantly reduced fractional
      anisotropy in bilateral superior longitudinal fasciculus, bilateral anterior
      corona radiata, and the left genu of the corpus callosum were shown in the PIGD
      subtype compared with the non-PIGD subtype. Increased radial diffusivity in the
      left superior longitudinal fasciculus was found in the PIGD subtype with no
      statistical differences in axial diffusivity found. CONCLUSIONS: Our study
      confirms previous findings that white matter abnormalities were greater in the
      PIGD subtype than in the non-PIGD subtype. Additionally, our findings suggested:
      (1) compared with the non-PIGD subtype, loss of white matter integrity was
      greater in the PIGD subtype; (2) bilateral superior longitudinal fasciculus may
      play a critical role in microstructural white matter abnormalities in the PIGD
      subtype; and (3) reduced white matter integrity in the PIGD subtype could be
      mainly attributed to demyelination rather than axonal loss.

PMID- 25377627
TI  - Spreading and sustaining best practices for home care of older adults: a grounded
      theory study.
AB  - BACKGROUND: Improving health care quality requires effective and timely spread of
      innovations that support evidence-based practices. However, there is limited
      rigorous research on the process of spread, factors influencing spread, and
      models of spread. It is particularly important to study spread within the home
      care sector given the aging of the population, expansion of home care services
      internationally, the high proportion of older adult users of home care services,
      and the vulnerability of this group who are frail and live with multiple chronic
      conditions. The purpose of this study was to understand how best practices
      related to older adults are spread within home care organizations. METHODS: Four
      home care organizations in Ontario, Canada that had implemented best practices
      related to older adults (falls prevention, pain management, management of venous
      leg ulcers) participated. Using a qualitative grounded theory design, interviews
      were conducted with frontline providers, managers, and directors at baseline (n =
      44) and 1 year later (n = 40). Open, axial, and selective coding and constant
      comparison analysis were used. RESULTS: A model of the process of spread of best
      practices within home care organizations was developed. The phases of spread
      included (1) committing to change, (2) implementing on a small scale, (3)
      adapting locally, (4) spreading internally to multiple users and sites, and (5)
      disseminating externally. Factors that facilitated progression through these
      phases were (1) leading with passion and commitment, (2) sustaining strategies,
      and (3) seeing the benefits. Project leads, champions, managers, and steering
      committees played vital roles in leading the spread process. Strategies such as
      educating/coaching and evaluating and feedback were key to sustaining the change.
      Spread occurred within the home care context of high staff and manager turnover
      and time and resource constraints. CONCLUSIONS: Spread of best practices is
      optimized through the application of the phases of spread, allocation of
      resources to support spread, and implementing strategies for ongoing
      sustainability that address potential barriers. Further research will help to
      understand how best practices are spread externally to other organizations.

PMID- 25377628
TI  - Single-breath analysis using a novel simple sampler and capillary electrophoresis
      with contactless conductometric detection.
AB  - The analysis of ionic content of exhaled breath condensate (EBC) from one single
      breath by CE with C(4) D is demonstrated for the first time. A miniature sampler
      made from a 2-mL syringe and an aluminum cooling cylinder for collection of EBC
      was developed. Various parameters of the sampler that influence its collection
      efficiency, repeatability, and effect of respiratory patterns were studied in
      detail. Efficient procedures for the cleanup of the miniature sampler were also
      developed and resulted in significant improvement of sampling repeatability.
      Analysis of EBC was performed by CE-C(4) D in a 60 mM MES/l-histidine BGE with 30
      MUM CTAB and 2 mM 18-crown-6 at pH 6 and excellent repeatability of migration
      times (RSD < 1.3% (n = 7)) and peak areas (RSD < 7% (n = 7)) of 12 inorganic
      anions, cations, and organic acids was obtained. It has been shown that the
      breathing pattern has a significant impact on the concentration of the analytes
      in the collected EBC. As the ventilatory pattern can be easily controlled during
      single exhalation, the developed collection system and method provides a highly
      reproducible and fast way of collecting EBC with applicability in point-of-care
      diagnostics. 

PMID- 25377629
TI  - Interventions to increase physician efficiency and comfort with an electronic
      health record system.
AB  - OBJECTIVE: To determine comfort when using the Electronic Health Record (EHR) and
      increase in documentation efficiency after an educational intervention for
      physicians to improve their transition to a new EHR. METHODS: This study was a
      single-center randomized, parallel, non-blinded controlled trial of real-time,
      focused educational interventions by physician peers in addition to usual
      training in the intervention arm compared with usual training in the control arm.
      Participants were 44 internal medicine physicians and residents stratified to
      groups using a survey of comfort with electronic media during rollout of a system
      wide EHR and order entry system. Outcomes were median time to complete a progress
      note, notes completed after shift, and comfort with EHR at 20 and 40 shifts.
      RESULTS: In the intervention group, 73 education sessions averaging 14.4 (SD:
      7.7) minutes were completed with intervention group participants, who received an
      average of 3.47 (SD: 2.1) interventions. Intervention group participants
      decreased their time to complete a progress note more quickly than controls over
      30 shifts (p < 0.001) and recorded significantly fewer progress notes after
      scheduled duty hours (77 versus 292, p < 0.001). Comfort with EHRs increased
      significantly in both groups from baseline but did not differ significantly by
      group. Intervention group participants felt that the intervention was more
      helpful than their standard training (3.47 versus 1.95 on 4-point scale).
      CONCLUSION: Physicians teaching physicians during clinical work improved
      physician efficiency but not comfort with EHRs. More study is needed to determine
      best methods to assist those most challenged with new EHR rollouts.

PMID- 25377630
TI  - sec-Butyl-propylacetamide (SPD) and two of its stereoisomers rapidly terminate
      paraoxon-induced status epilepticus in rats.
AB  - OBJECTIVE: Organophosphates (OPs) are commonly used insecticides for agriculture
      and domestic purposes, but may also serve as nerve agents. Exposure to OPs result
      in overstimulation of the cholinergic system and lead to status epilepticus (SE),
      a life-threatening condition that is often resistant to treatment. SE is
      associated with significant neuronal damage, neurocognitive dysfunction, and the
      development of lifelong epilepsy. Therefore, rapid termination of SE and
      prevention of brain damage is of high interest. Here we tested the efficacy of
      sec-butyl-propylacetamide (SPD) and two of its individual stereoisomers, (2S,3S)
      SPD and (2R,3R)-SPD, in discontinuing OP-induced seizures. SPD is a one carbon
      homolog of valnoctamide, a central nervous system (CNS)-active constitutional
      isomer of valproic acid (VPA) corresponding amide valpromide. METHODS: Rats were
      implanted with epidural telemetric electrodes to allow electrocorticography
      (ECoG) recording 24 h prior, during and 24 h after poisoning with the OP paraoxon
      (at a dose equivalent to 1.4 LD50 Median lethal dose). All rats were provided
      with antidotal treatment of atropine and toxogonin. Epileptic activity was
      measured using a novel automated system to evaluate the different effects of
      midazolam, SPD, and its individual stereoisomers in comparison to nontreated
      controls. RESULTS: Treatment with SPD or its individual stereoisomer (2S,3S)-SPD
      significantly shorten paraoxon-induced SE and reduced the duration of recorded
      pathologic activity after SE was terminated. (2S,3S)-SPD was superior to racemic
      SPD in diminishing delayed pathologic epileptiform activity within the first 8 h
      after SE. SIGNIFICANCE: These results suggest SPD as an efficient drug for the
      rapid termination of SE and pathological epileptiform activity following OP
      poisoning, a strategy to reduce neuronal dysfunction and the risk for lifelong
      epilepsy.

PMID- 25377631
TI  - Google Glass, ultrasound and palpation: the anatomy teacher of the future?
AB  - Traditional palpation techniques are used less often in today's modern medical
      arena. Technological advances in imaging, for example, often supplant the need
      for such types of tactility. Herein, we discuss our recent experience using
      Google Glass in the teaching of anatomy to medical students, a method that melds
      traditional medical palpation with cutting edge technology. Based on our study,
      teachers of the new millennium might use Google Glass coupled with ultrasound and
      palpation in the teaching of human anatomy to medical students. Such a technology
      combines palpation, diagnosis, visualization, and learning of anatomy. Glass has
      provided a platform to position a live ultrasound image for us to view while
      examining the patient. This technology will allow the physicians of the future to
      embrace placing ones hand on the body while receiving both palpation and visual
      stimulation.

PMID- 25377632
TI  - The need for toric intra-ocular lens implantation in public ophthalmology
      departments.

PMID- 25377633
TI  - Spatially resolved one-dimensional boundary states in graphene-hexagonal boron
      nitride planar heterostructures.
AB  - Two-dimensional interfaces between crystalline materials have been shown to
      generate unusual interfacial electronic states in complex oxides. Recently, a one
      dimensional interface has been realized in hexagonal boron nitride and graphene
      planar heterostructures, where a polar-on-nonpolar one-dimensional boundary is
      expected to possess peculiar electronic states associated with edge states of
      graphene and the polarity of boron nitride. Here we present a combined scanning
      tunnelling microscopy and first-principles theory study of the graphene-boron
      nitride boundary to provide a first glimpse into the spatial and energetic
      distributions of the one-dimensional boundary states down to atomic resolution.
      The revealed boundary states are about 0.6 eV below or above the Fermi level
      depending on the termination of the boron nitride at the boundary, and are
      extended along but localized at the boundary. These results suggest that
      unconventional physical effects similar to those observed at two-dimensional
      interfaces can also exist in lower dimensions. 

PMID- 25377634
TI  - IL2-IL21 gene cluster polymorphism is not associated with allograft function
      after kidney transplantation.
AB  - BACKGROUND: Cytokines are key mediators of the immune response after
      transplantation. The interleukin (IL)-2 cytokine family, which includes IL-2, IL
      4, IL-7, IL-9, IL-15, and IL-21, is of particular interest because of its
      importance in the allogenic response. The aim of this study was to examine the
      association between the rs6822844 gene polymorphism in the IL2-IL21 region and
      allograft function after kidney transplantation. METHODS: The study enrolled 270
      Caucasian kidney allograft recipients (166 males and 104 females, mean age 47.63
      +/- 12.96 years). Following parameters were recorded in each case: recipient's
      age, delayed graft function (DGF), occurrence and number of episodes of acute
      rejection (AR), and chronic allograft dysfunction (CAD). Genotyping of the
      rs6822844 IL2-IL21 cluster gene polymorphism was performed using real-time PCR
      assay. RESULTS: There were no statistically significant differences in the
      genotypes and alleles of the rs6822844 IL2-IL21 cluster gene polymorphism among
      patients with DGF (p = 0.72), AR (p = 0.69) and CAD (p = 0.77), or in creatinine
      concentrations 1, 3, 6, 12, 24 or 36 months after transplantation (p = 0.46, p =
      0.58, p = 0.6, p = 0.72, p = 0.7, p = 0.76, respectively). CONCLUSION: It seems
      that the rs6822844 IL2-IL21 gene cluster polymorphism is of little importance in
      allograft function after kidney transplantation.

PMID- 25377635
TI  - Characterization of homologous and heterologous interactions between viroplasm
      proteins P6 and P9-1 of the fijivirus southern rice black-streaked dwarf virus.
AB  - P6 of southern rice black-streaked dwarf virus (SRBSDV) is a multifunctional
      protein that is involved in the formation of viroplasms by interacting with P5-1.
      Here, we used yeast two-hybrid and bimolecular fluorescence complementation
      assays to show that there were homologous and heterologous interactions between
      SRBSDV P6 and P9-1 in yeast and plant cells. Mutational analysis showed that the
      N-terminal region (residues 1-93) of P6 was necessary for the interaction between
      P6 and P9-1. Self-interactions only occurred between the full-length P6 or P9-1.
      P9-1 was able to form viroplasm-like inclusion structures alone in the absence of
      other viral proteins. 

PMID- 25377636
TI  - Phylogenetic analysis of a G6P[5] bovine rotavirus strain isolated in a neonatal
      diarrhea outbreak in a beef cattle herd vaccinated with G6P[1] and G10P[11]
      genotypes.
AB  - The aim of this study was to perform the molecular characterization of the eleven
      genes of a G6P[5] bovine group A rotavirus (RVA) strain detected in a diarrhea
      outbreak from a vaccinated beef cattle herd. The outbreak affected 80 % of calves
      between 15-30 days old. RVA was identified by RT-PCR in 12 (70.6 %) out of 17
      diarrheic fecal samples evaluated. The rotavirus wild-type strain had the
      genotype constellation G6(IV)-P[5](IX)-I2c-R2-C2-M2-A3-N2-T6-E2e-H3a. This study
      confirms the importance of homotypic immunity against the bovine RVA P[5]
      genotype in neonatal diarrhea in cattle herds that are regularly vaccinated
      against rotaviruses. 

PMID- 25377637
TI  - Three-dimensional structure of foot-and-mouth disease virus and its biological
      functions.
AB  - Foot-and-mouth disease (FMD), an acute, violent, infectious disease of cloven
      hoofed animals, remains widespread in most parts of the world. It can lead to a
      major plague of livestock and an economical catastrophe. Structural studies of
      FMD virus (FMDV) have greatly contributed to our understanding of the virus life
      cycle and provided new horizons for the control and eradication of FMDV. To
      examine host-FMDV interactions and viral pathogenesis from a structural
      perspective, the structures of viral structural and non-structural proteins are
      reviewed in the context of their relevance for virus assembly and dissociation,
      formation of capsid-like particles and virus-receptor complexes, and viral
      penetration and uncoating. Moreover, possibilities for devising novel antiviral
      treatments are discussed. 

PMID- 25377638
TI  - Malignant meningioma with adenocarcinoma-like metaplasia: demonstration of
      intestinal phenotype.
AB  - Meningiomas show a diverse histopathologic appearance, often referred to as
      metaplastic changes; however, adenocarcinoma-like metaplasia is an extremely rare
      condition. Here, we present a novel case. A dura-based bulky mass located in the
      right frontotemporal region was identified radiologically in an 83-year-old
      woman. The tumor, yellow to ash-gray in color, was subtotally removed.
      Histopathological examination revealed robust adenocarcinoma-like structures
      within a conventional meningothelial neoplasm. Meningioma elements showed a WHO
      grade I to III histology. Morphological and immunophenotypic transition between
      meningothelial and columnar epithelial cells was confirmed on detailed
      observation. It was of note that the adenocarcinomatous components shared an
      immunophenotype with intestinal epithelium, expressing CDX2, MUC2 and cytokeratin
      20. The present case could be differentiated from secretory meningioma based on
      distinct cellular atypia, lack of intracytoplasmic lumina and pseudosammoma
      bodies, and the intact status of the KLF4 gene. In addition, the morphological
      and immunophenotypic transition excluded the possibility of metastatic carcinoma
      within meningioma. This is the first reported case of meningioma with
      adenocarcinoma-like metaplasia harboring an intestinal immunophenotype.

PMID- 25377640
TI  - Institutional learning curve of cytoreductive surgery and hyperthermic
      intraperitoneal chemoperfusion for peritoneal malignancies.
AB  - BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal
      chemoperfusion (HIPEC) is routinely used to treat certain peritoneal
      carcinomatoses (PC), but it can be associated with relatively high complication
      rates, prolonged hospital length of stay, and potential mortality. Our objective
      was to determine the learning curve (LC) of CRS/HIPEC in our high-volume
      institution. METHODS: A total of 370 patients with PC from mucinous appendiceal
      neoplasms (MAN = 282), malignant peritoneal mesothelioma (MPM = 60), and gastric
      cancer (GC = 24) were studied. Outcomes analyzed included incomplete
      cytoreduction (IC), severe morbidity (SM), 60-day mortality, progression-free
      survival (PFS), and overall survival (OS). Risk-adjusted sequential probability
      ratio test (RA-SPRT) was employed to assess the LC of CRS/HIPEC for IC and SM
      using prespecified odds ratio (OR) boundaries derived from previously published
      data. Risk adjusted-cumulative average probability (RA-CAP) was used to analyze 1
      year PFS and 2-year OS. RESULTS: Complete cytoreduction, severe morbidity, and 60
      day mortality were 84.2, 30, and 1.9 % respectively. Higher simplified peritoneal
      cancer index was the major independent risk factor for IC, whereas high-grade
      histology, IC, and diagnosis of MPM and GC (compared with MAN) were predictors of
      SM after CRS/HIPEC (p < 0.05). RA-SPRT showed that approximately 180 cases are
      needed to achieve the lowest risk of IC and SM. Ninety cases were needed to
      achieve a steady 1-year PFS and 2-year OS in RA-CAP plots. CONCLUSIONS: The
      completeness of cytoreduction, morbidity, and mortality rates for CRS/HIPEC at
      our institution are comparable to previously reported data. Approximately 180 and
      90 procedures are required to improve operative and oncologic outcomes
      respectively.

PMID- 25377639
TI  - Eye-specific retinogeniculate segregation proceeds normally following disruption
      of patterned spontaneous retinal activity.
AB  - BACKGROUND: Spontaneous retinal activity (SRA) is important during eye-specific
      segregation within the dorsal lateral geniculate nucleus (dLGN), but the
      feature(s) of activity critical for retinogeniculate refinement are
      controversial. Pharmacologically or genetically manipulating cholinergic
      signaling during SRA perturbs correlated retinal ganglion cell (RGC) spiking and
      disrupts eye-specific retinofugal refinement in vivo, consistent with an
      instructive role for SRA during visual system development. Paradoxically,
      ablating the starburst amacrine cells (SACs) that generate cholinergic
      spontaneous activity disrupts correlated RGC firing without impacting retinal
      activity levels or eye-specific segregation in the dLGN. Such experiments suggest
      that patterned SRA during retinal waves is not critical for eye-specific
      refinement and instead, normal activity levels are permissive for
      retinogeniculate development. Here we revisit the effects of ablating the
      cholinergic network during eye-specific segregation and show that SAC ablation
      disrupts, but does not eliminate, retinal waves with no concomitant impact on
      normal eye-specific segregation in the dLGN. RESULTS: We induced SAC ablation in
      postnatal ferret pups beginning at birth by intraocular injection of a novel
      immunotoxin selective for the ferret vesicular acetylcholine transporter (Ferret
      VAChT-Sap). Through dual-patch whole-cell and multi-electrode array recording we
      found that SAC ablation altered SRA patterns and led to significantly smaller
      retinal waves compared with controls. Despite these defects, eye-specific
      segregation was normal. Further, interocular competition for target territory in
      the dLGN proceeded in cases where SAC ablation was asymmetric in the two eyes.
      CONCLUSIONS: Our data demonstrate normal eye-specific retinogeniculate
      development despite significant abnormalities in patterned SRA. Comparing our
      current results with earlier studies suggests that defects in retinal wave size,
      absolute levels of SRA, correlations between RGC pairs, RGC burst frequency, high
      frequency RGC firing during bursts, and the number of spikes per RGC burst are
      each uncorrelated with abnormalities in eye-specific segregation in the dLGN. An
      increase in the fraction of asynchronous spikes occurring outside of bursts and
      waves correlates with eye-specific segregation defects in studies reported to
      date. These findings highlight the relative importance of different features of
      SRA while providing additional constraints for computational models of Hebbian
      plasticity mechanisms in the developing visual system.

PMID- 25377641
TI  - Influence of Er(3+) concentration on the photoluminescence characteristics and
      excitation mechanism of Gd2O3:Er(3+) phosphor synthesized via a solid-state
      reaction method.
AB  - An Er(3+) -doped phosphor of Gd2O3(Gd2O3:Er(3+)) was prepared using a
      conventional solid-state reaction method. The structure and particle size were
      determined from X-ray powder diffraction measurements. The average particle size
      of the phosphor was in between 20 and 50 nm. The particle size and structure of
      the phosphor were further confirmed by transmission electron microscopy (TEM)
      analysis. Luminescence spectra were recorded under excitation wavelengths of 275,
      380, 515 and 980 nm. The visible upconversion and downconversion luminescence
      spectra of the Gd2O3:Er(3+) phosphor were investigated as a function of Er(3+)
      ion concentration. The upconverted emission at 980 nm excitation shows enhanced
      red emission with respect to green emission as the dopant concentration
      increased. Similar results were observed for downconversion emission under 275
      and 380 nm excitation wavelengths. The mechanisms responsible for populating the
      (4)S3/2 and (4)F9/2 levels, for green and red emissions, respectively, are
      different for different excitations and for different concentrations of Er(3+).

PMID- 25377642
TI  - Differential regulation of AChR clustering in the polar and equatorial region of
      murine muscle spindles.
AB  - Intrafusal fibers of muscle spindles are innervated in the central region by
      afferent sensory axons and at both polar regions by efferent gamma-motoneurons.
      We previously demonstrated that both neuron-muscle contact sites contain
      cholinergic synapse-like specialisation, including aggregates of the nicotinic
      acetylcholine receptor (AChR). In this study we tested the hypothesis that agrin
      and its receptor complex (consisting of LRP4 and the tyrosine kinase MuSK) are
      involved in the aggregation of AChRs in muscle spindles, similar to their role at
      the neuromuscular junction. We show that agrin, MuSK and LRP4 are concentrated at
      the contact site between the intrafusal fibers and the sensory- and gamma
      motoneuron, respectively, and that they are expressed in the cell bodies of
      proprioceptive neurons in dorsal root ganglia. Moreover, agrin and LRP4, but not
      MuSK, are expressed in gamma-motoneuron cell bodies in the ventral horn of the
      spinal cord. In agrin- and in MuSK-deficient mice, AChR aggregates are absent
      from the polar regions. In contrast, the subcellular concentration of AChRs in
      the central region where the sensory neuron contacts the intrafusal muscle fiber
      is apparently unaffected. Skeletal muscle-specific expression of miniagrin in
      agrin(-/-) mice in vivo is sufficient to restore the formation of gamma
      motoneuron endplates. These results show that agrin and MuSK are major
      determinants during the formation of gamma-motoneuron endplates but appear
      dispensable for the aggregation of AChRs at the central region. Our results
      therefore suggest different molecular mechanisms for AChR clustering within two
      domains of intrafusal fibers. 

PMID- 25377643
TI  - Sequence analysis of the Ras-MAPK pathway genes SOS1, EGFR & GRB2 in silver foxes
      (Vulpes vulpes): candidate genes for hereditary hyperplastic gingivitis.
AB  - Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive disease that
      presents with progressive gingival proliferation in farmed silver foxes.
      Hereditary gingival fibromatosis (HGF) is an analogous condition in humans that
      is genetically heterogeneous with several known autosomal dominant loci. For one
      locus the causative mutation is in the Son of sevenless homologue 1 (SOS1) gene.
      For the remaining loci, the molecular mechanisms are unknown but Ras pathway
      involvement is suspected. Here we compare sequences for the SOS1 gene, and two
      adjacent genes in the Ras pathway, growth receptor bound protein 2 (GRB2) and
      epidermal growth factor receptor (EGFR), between HHG-affected and unaffected
      foxes. We conclude that the known HGF causative mutation does not cause HHG in
      foxes, nor do the coding regions or intron-exon boundaries of these three genes
      contain any candidate mutations for fox gum disease. Patterns of molecular
      evolution among foxes and other mammals reflect high conservation and strong
      functional constraints for SOS1 and GRB2 but reveal a lineage-specific pattern of
      variability in EGFR consistent with mutational rate differences, relaxed
      functional constraints, and possibly positive selection. 

PMID- 25377644
TI  - Effects of feeding polyphenol-rich winery wastes on digestibility, nitrogen
      utilization, ruminal fermentation, antioxidant status and oxidative stress in
      wethers.
AB  - Four wethers were used in a 4 * 4 Latin square design experiment to evaluate the
      availability of two types of winery wastes, winery sediment and grape pomace, as
      ruminant feeds possessing antioxidant activities. Each wether was assigned to one
      of the following four treatments: (i) 75 g/kg winery sediment (WS) on a dry
      matter (DM) basis; (ii) 166 g/kg DM winery grape pomace (WP); (iii) control diet
      (CD; 17 g/kg DM soybean meal);and (iv) only tall fescue hay (TFH; no additive).
      Winery sediment and grape pomace had high levels of polyphenols and of radical
      scavenging activities. Feeding with winery sediment and grape pomace did not
      negatively affect the intake, but it depressed crude protein (CP) digestibility
      compared with CD (P = 0.052 and P < 0.01 for WS and WP, respectively).
      Polyphenols in winery wastes decreased ruminal ammonia production (P = 0.089 and
      P < 0.05), likely due to their inhibitive effect on microbial activities in the
      rumen. The addition of winery sediment and grape pomace decreased urinary 8
      hydroxy-2'-deoxyguanosine (8-OHdG; an index of oxidative damages) excretion per
      day (P < 0.05 and P = 0.059). The results indicated that winery sediment and
      grape pomace could alter nitrogen metabolism and/or act as new antioxidants for
      ruminants. 

PMID- 25377645
TI  - Polymorphisms in the vitamin D receptor and risk of gout in Chinese Han male
      population.
AB  - Previous studies have showed that patients with gout showed lower serum 25(OH)D
      levels. As the specific receptor of vitamin D, VDR plays an important role in
      regulating immune system by combining with vitamin D. In this study, we
      investigated whether the functional VDR polymorphisms were associated with
      susceptibility to gout in Chinese Han male population. A total of 504 patients
      with gout and 523 gout-free controls were recruited from the Affiliated Hospital
      of the Medical College, Qingdao University. Genotyping of VDR rs11568820,
      rs2228570 and rs1544410 was performed by TaqMan allele discrimination assays. An
      association analysis was carried out using the chi(2) test. A genotype-phenotype
      analysis was also conducted. Our results showed that polymorphisms of rs11568820
      and rs1544410 in VDR were associated with gout in Chinese Han male population.
      The A allele of both rs11568820 and rs1544410 was associated with the risk of
      gout [P = 0.012 OR 1.251, 95% CI (1.051-1.490); P = 0.006, OR 1.574, 95% CI
      (1.139-2.175)]. However, there was no statistic significance between rs2228570
      and gout (P = 0.186). Our study suggested that the polymorphisms of VDR may be
      relevant host susceptibility factors for the development of gout in Chinese Han
      male population. However, further study should be done in a larger size sample
      and other ethic to test and verify our result.

PMID- 25377646
TI  - Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and
      systemic lupus erythematosus: a potentially useful tool in differential
      diagnosis.
AB  - Making a correct diagnosis is pivotal in the practice of clinical rheumatology.
      Occasionally, the consultation fails to provide desired clarity in making
      labeling an individual as having fibromyalgia (FM), systemic lupus erythematosus
      (SLE) or rheumatoid arthritis (RA). A chemokine and cytokine multiplex assay was
      developed and tested with the goal of improving and achieving an accurate
      differential diagnosis. 160 patients with FM, 98 with RA and 100 with SLE
      fulfilling accepted criteria were recruited and compared to 119 controls.
      Supernatant cytokine concentrations for IL-6, IL-8, MIP-1 alpha and MIP-1 beta
      were determined using the Luminex multiplex immunoassay bead array technology
      after mitogenic stimulation of cultured peripheral blood mononuclear cells. Each
      patient's profile was scored using a logistical regression model to achieve
      statistically determined weighting for each chemokine and cytokine. Among the 477
      patients evaluated, the mean scores for FM (1.7 +/- 1.2; 1.52-1.89), controls (
      3.56 +/- 5.7; -4.59 to -2.54), RA (-0.68 +/- 2.26; -1.12 to -0.23) and SLE (-1.45
      +/- 3.34, -2.1 to -0.79). Ninety-three percent with FM scored positive compared
      to only 11% of healthy controls, 69% RA or 71% SLE patients had negative scores.
      The sensitivity, specificity, positive predictive and negative predictive value
      for having FM compared to controls was 93, 89, 92 and 91%, respectively (p < 2.2
      * 10(-16)). Evaluating cytokine and chemokine profiles in stimulated cells
      reveals patterns that are uniquely present in patients with FM. This assay can be
      a useful tool in assisting clinicians in differentiating systemic inflammatory
      autoimmune processes from FM and its related syndromes and healthy individuals.

PMID- 25377647
TI  - Managing anxiety and depression during treatment.
AB  - Here, we review the prevalence and treatment of anxiety and depression among
      patients with breast cancer. Cancer-related symptoms include similarities to
      responses to traumatic stress. Well-developed screening devices for identifying
      and tracking psychiatric comorbidity are discussed. Basic principles of
      psychopharmacology, and individual and group psychotherapy are presented.
      Finally, effects of effective treatment of anxiety and depression on quality of
      life and overall survival are reviewed. 

PMID- 25377648
TI  - Time from nephrectomy as a prognostic factor in metastatic renal cell carcinoma
      patients receiving targeted therapies: overall results from a large cohort of
      patients.
AB  - OBJECTIVE: To investigate whether time from nephrectomy (Nx) to the diagnosis of
      metastatic disease may be an independent prognostic factor in metastatic renal
      cell carcinoma (mRCC) patients treated with targeted therapies (TTs). SUBJECTS
      AND METHODS: All patients who underwent Nx and at least 1 TT were considered. The
      patients were divided into two groups based on time from Nx [>1 year (Nx >1) and
      <1 year (Nx <1)] and a third group for cytoreductive Nx (cNx). Median overall
      survival (OS) represented the primary outcome. RESULTS: A total of 297 patients
      met the inclusion criteria. The time from Nx was >1 year in 47%, <1 year in 26%
      and concomitant with the diagnosis of metastatic disease in 27% of the cases
      (i.e. cNx). The median OS was 40.6 months (95% CI 30.5-50.7) for the Nx >1 group,
      24.3 months (95% CI 17.7-31) for the Nx <1 group and 16.2 months (95% CI 11.2
      21.3) for the cNx group (p < 0.05 for all comparisons). On multivariate analysis,
      time from Nx resulted to be an independent prognostic factor (Nx <1 vs. cNx: HR =
      0.62, 95% CI 0.42-0.90, p = 0.13; Nx >1 vs. cNx: HR = 0.43, 95% CI 0.31-0.61, p <
      0.001). CONCLUSION: We report that time from Nx is an independent prognostic
      factor for OS in patients affected by mRCC treated with TTs.

PMID- 25377649
TI  - Impact of the free-vaccine policy on timely initiation and completion of
      hepatitis B vaccination in Fujian, China.
AB  - The extent to which the free-vaccine policy impacts the initiation and completion
      of a hepatitis B vaccine series is poorly understood. The aim of this study was
      to evaluate the impact of the free-vaccine policy on hepatitis B vaccination. A
      provincial survey was conducted in 2006 in Fujian Province, south-east of China,
      where the free-vaccine policy for hepatitis B was announced in 2002 and
      implemented in 2003. A total of 1628 children were investigated, and 1443 (88.6%)
      were included in this analysis. Among the children studied, 55.2% were vaccinated
      within 24 h of birth, and 76.1% completed the hepatitis B vaccine series on time.
      The rate of hepatitis B surface antibody positivity increased from 29.9% among
      children born in 1992 to 90.5% among children born in 2005, while the
      corresponding HBV infection rate decreased from 30.4% to 1.72%. Logistic
      regression indicated that, compared to children born between 1996 and 2001, the
      odds ratios (ORs) for timely initiation were 2.57 (95% confidence interval [CI],
      1.71-3.84), 5.24 (95% CI, 3.26-8.43) and 9.06 (95% CI, 4.48-18.34) among children
      born in 2003, 2004 and 2005, respectively; the corresponding ORs for completing
      the vaccine series were 4.23 (95% CI, 1.97-9.10), 3.76 (95% CI, 1.81-7.82) and
      4.94 (95% CI, 1.74-14.00) among children born in 2003, 2004 and 2005,
      respectively. Children with delayed vaccine initiation (>24 h after birth) were
      less likely to complete the vaccine series than those who received a timely first
      dose (OR = 0.02, 95% CI, 0.005-0.09). The impact of the free-vaccine policy on
      vaccine initiation and vaccine series completion did not differ by children's
      residence area (rural vs urban). As hypothesized, the odds of completing the
      vaccine series increased after the free-vaccine policy was announced in 2002
      among children with delayed initiation (>24 h after birth) but not among those
      with timely initiation (<= 24 h after birth). In conclusion, the free-vaccine
      policy significantly improved the timely initiation and completion of the vaccine
      series. The impact of this policy on completion of the vaccine series was larger
      among children with delayed vaccine initiation.

PMID- 25377650
TI  - Anticancer profile of a series of gold(III) (2-phenyl)pyridine complexes.
AB  - Six phosphorescent (2-phenyl)pyridine (ppy) gold(III) 2,4,6
      tris(trifluoromethyl)phenyl (FMes) complexes were synthesized and investigated
      for their anticancer potential. The compounds demonstrated strong
      antiproliferative activity, with EC50 values in the low micromolar range, along
      with significant accumulation in HeLa cancer cells after treatment for only 6 h
      (up to 119 ng gold per milligram of protein as measured by high-resolution
      continuum source atomic spectroscopy). Enzyme inhibition studies showed
      interaction of the gold(III) complexes with thioredoxin reductase (TrxR), a key
      homeostasis-regulation flavoprotein. TrxR was inhibited with IC50 values in the
      micromolar range. Furthermore, five of the complexes displayed selectivity toward
      TrxR against glutathione reductase (GR, a disulfide reductase structurally
      related to TrxR) by up to >49-fold. Because no major differences in bioactivity
      were observed across the series, [(ppy)Au(FMes)(PPh3 )OTf] (complex 4) was chosen
      for further in-depth biological characterization. Complex 4 was also found to
      interact with guanosine monophosphate in (1) H NMR studies under long incubation
      times. Interestingly, 4 induced a significant increase in intracellular levels of
      reactive oxygen species, which led to late apoptotic events and cytocidal
      effects.

PMID- 25377652
TI  - Basophil responses to peanut allergens.

PMID- 25377651
TI  - Major changes in diagnosis and management of preeclampsia.
AB  - Preeclampsia and eclampsia continue to be major contributors to maternal
      mortality and morbidity. Lack of appreciation for the multi-organ involvement of
      preeclampsia, combined with overly rigid criteria for diagnosis, may hinder early
      diagnosis and appropriate management. Recently, the American College of
      Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy evaluated
      the evidence and formulated new recommendations for diagnosis and management.
      This article reviews some of these recommended changes, including the new
      classification of the hypertensive diseases of pregnancy. Systolic blood pressure
      has been shown to be as important as diastolic blood pressure in the diagnosis of
      preeclampsia. Changes in proteinuria are not predictive of disease severity or
      maternal or fetal complications; therefore, the magnitude of proteinuria or
      changes in the amount should not dictate diagnosis or management. Instead,
      symptoms of cerebral involvement, such as headache and visual changes or signs of
      end-organ involvement including abnormal laboratory tests (elevated serum
      creatinine or liver function tests, low platelet count), are evidence of
      preeclampsia with severe features. Immediate induction of labor is recommended
      for women with gestational hypertension or preeclampsia at 37 weeks' gestation or
      later. Pregnant and postpartum women need to know important warning signs and
      symptoms of preeclampsia. Prompt diagnosis of preeclampsia and appropriate
      management will improve the quality of care for women. 

PMID- 25377653
TI  - Water and electrolyte disorders at long-term post-treatment follow-up in
      paediatric patients with suprasellar tumours include unexpected persistent
      cerebral salt-wasting syndrome.
AB  - BACKGROUND: Patients with brain tumours have a high risk of water and electrolyte
      disorders (WED). Postsurgery diabetes insipidus (DI) may be transient or
      permanent, the syndrome of inappropriate antidiuretic hormone secretion (SIADH)
      and cerebral salt-wasting syndrome (CSWS) are usually transient. METHODS:
      Retrospective study, including patients with suprasellar tumours, treated at
      Hopital Necker, Institut Gustave-Roussy or Institut Curie, in Ile-de-France,
      between 2007 and 2011. WED were noted if they persisted >1 month after surgery.
      RESULTS: 159 patients were included, 54.1% girls, 43.9% boys. Tumour types were:
      glioma (43.4%), craniopharyngioma (43.4%), germinoma (11.3%), others (1.9%). Age
      at diagnosis was 7.1 +/- 4.6 years. The median time from end of treatment was 1.9
      (0-7.8) years. DI was the most frequent disorder after tumour treatment (50.3%)
      and was significantly associated with surgery (p < 0.001). Persistent CSWS was
      present in 3.6%, persistent SIADH in 1.3%. Two cases of hypernatraemia were due
      to adipsia. Thyrotropin deficiency after treatment was noted in 68.9% of patients
      tested, adrenocorticotropin deficiency in 66.2%. CONCLUSIONS: Patients with
      suprasellar tumours have a high incidence of long-term WED, mainly DI. Assessment
      of thyrotroph and corticotroph function, and thirst sensation, is necessary to
      diagnose and manage these disorders correctly. CSWS may be persistent in few
      patients and requires special attention to prescribe the appropriate care.

PMID- 25377654
TI  - Identification of cornifelin and early growth response-1 gene as novel biomarkers
      for in vitro eye irritation using a 3D reconstructed human cornea model MCTT
      HCETM.
AB  - Evaluation of the eye irritation is essential in the development of new cosmetic
      products. Draize rabbit eye irritation test has been widely used in which
      chemicals are directly applied to rabbit eye, and the symptoms and signs of eyes
      are scored. However, due to the invasive procedure, it causes substantial pain
      and discomfort to animals. Recently, we reported in vitro eye irritation test
      method using a 3D human corneal epithelial model (MCTT HCETM) which is
      reconstructed from remaining human tissues after a corneal transplantation. This
      model exhibited an excellent predictive capacity for 25 reference chemicals
      (sensitivity 100%, specificity 77% and accuracy 88% vs. GHS). To improve the test
      performance, we explored new biomarkers for the eye irritation through
      transcriptomic approach. Three surfactants were selected as model eye irritants
      that include sodium lauryl sulfate, benzalkonium chloride and triton X-100. After
      test chemicals were treated, we investigated differentially expressed genes
      through a whole-gene microarray (Affymetrix GeneChip((r)) Human Gene 2.0 ST
      Array, 48,000 probes). As a result, we identified that mRNAs of cornifelin
      (CNFN), a constituent of the insoluble cornified cell envelope of stratified
      squamous epithelia, and early growth response-1 (EGR1), a nuclear transcriptional
      regulator, were significantly up-regulated by all three irritants. Up-regulation
      of CNFN and EGR1 was further confirmed by Q-RT-PCR, and immunohistochemistry
      revealed increased level of CNFN in irritant-treated tissues, supporting the
      relevance of CNFN and EGR1 as new biomarkers for eye irritation.

PMID- 25377656
TI  - Resolution of anuric acute kidney injury in a dog with multiple organ dysfunction
      syndrome.
AB  - OBJECTIVE: To describe the management and resolution of anuric acute kidney
      injury (AKI) in a dog with multiple organ dysfunction syndrome (MODS) associated
      with gallbladder wall necrosis. CASE SUMMARY: An 11-year-old neutered female
      spayed dog was referred for evaluation of anuria following cholecystectomy.
      Following surgery, the patient became anuric with no response to appropriate
      medical therapy. During the course of hospitalization, the patient developed MODS
      as evidenced by alteration in renal function, but also cardiovascular
      dysfunction, coagulation disorders, and hypoglycemia. Several hemodialysis
      treatments were performed and, along with intensive care, led to resolution of
      clinical signs and return of urine production. NEW OR UNIQUE INFORMATION: This
      report describes resolution of anuria in a dog with AKI and MODS. In this
      clinical setting, despite a poor prognosis, survival and recovery of adequate
      renal function were possible with medical management that included hemodialysis.

PMID- 25377657
TI  - Psoriasis and daily low-emission phototherapy: effects on disease and vitamin D
      level.
AB  - BACKGROUND/PURPOSE: Hospital-based phototherapy is a widely accepted treatment
      modality in psoriasis patients. It, however, requires several hospital visits
      weekly, interfering with (school)work. Home ultraviolet (UV) treatment has been
      proven effective before but is only available in certain countries, and safety
      aspects play a part in reluctancy to prescribe this treatment. Patients, however,
      are usually keen on the use of phototherapy as it is effective and gives them the
      possibility of reducing the amount of topical treatment needed. In this study, we
      assess the effectivity of a low-emission UV device used daily. METHODS: Sixty-two
      patients were treated for 6 months either with daily low-emission UV treatment
      and mometasone ointment 0.1% or with mometasone ointment 0.1% alone. Psoriasis
      severity scores, quality of life, vitamin D level, and blood pressure were
      monitored every 2 months during the study. RESULTS: Patients treated with daily
      low-emission UV treatment showed a significant improvement in psoriasis severity,
      quality of life, amount of steroid ointment used, and vitamin D levels.
      CONCLUSION: Daily low-emission UV therapy is an effective treatment for psoriasis
      patients, diminishing the amount of steroid ointment needed and improving disease
      activity, quality of life, and vitamin D scores. Further investigation, however,
      is necessary.

PMID- 25377658
TI  - Cu(II) /TEMPO-promoted one-pot synthesis of highly substituted pyrimidines from
      amino acid esters.
AB  - A novel, Cu(OAc)2/TEMPO promoted one-step approach for the preparation of fully
      substituted pyrimidines from readily available amino acid esters has been
      described. In this reaction, the amino acid esters act as the only N-C sources
      for the construction of corresponding pyrimidines. The mechanism of this process
      includes oxidative dehydrogenation, the generation of an imine radical, and a
      formal [3+3] cycloaddition. This methodology proves to be a high atom-economic
      and straightforward strategy for the synthesis of pyrimidines and diverse
      substrates which are substituted by various functional groups have been afforded
      in moderate to good yield.

PMID- 25377659
TI  - Expression of HIF-1alpha and CAIX in nasopharyngeal carcinoma and their
      correlation with patients' prognosis.
AB  - This study investigates the expression of hypoxia-inducible factor-l alpha (HIF
      1alpha) and carbonic anhydrase IX (CAIX) in nasopharyngeal carcinoma (NPC)
      tissues and their correlation with clinicopathological features and prognosis in
      NPC patients. The expression of HIF-1alpha and CAIX proteins was detected by
      immunohistochemical staining in 129 samples of NPC and 20 samples of chronic
      nasopharyngitis. The correlations between the expression of these two proteins
      and clinicopathological features and prognosis were evaluated in NPC patients.
      Our results showed that the positive expression rates of HIF-1alpha and CAIX
      proteins in NPC were significantly higher than those in chronic nasopharyngitis
      (both P < 0.01). In addition, high HIF-1alpha protein expression was correlated
      with lymph node metastasis and advanced clinical stage for NPC patients (both P <
      0.01), whereas there were no findings of correlations between CAIX protein
      expression and gender, age, T stage, node involvement and clinical stage (all P >
      0.05). The Spearman analysis indicated that HIF-1alpha was positively correlated
      with CAIX expression (r = 0.249, P = 0.004). HIF-1alpha and CAIX co-expression
      was associated with the poor overall survival (OS), progression-free survival
      (PFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free
      survival (DMFS) in NPC patients (P = 0.017, P = 0.022, P = 0.033, and P = 0.017,
      respectively). Multivariate analysis showed that the positive expression of CAIX
      protein was an independent prognostic factor for PFS, LRRFS and DMFS. In
      conclusion, overexpression of HIF-1alpha and CAIX might be involved in the
      carcinogenesis and development of NPC and they were associated with patients'
      poor prognosis.

PMID- 25377660
TI  - Downregulated expression of PTK6 is correlated with poor survival in esophageal
      squamous cell carcinoma.
AB  - To investigate the clinical prognostic value of protein tyrosine kinase 6 (PTK6)
      in patients with esophageal squamous cell carcinoma (ESCC), quantitative RT-PCR
      and Western blotting were utilized to measure the mRNA and protein expression
      levels of PTK6 in 29 and eight pairs of ESCC and peritumoral normal esophageal
      tissues, respectively. Furthermore, the expression of PTK6 protein in 210 ESCCs
      was examined with immunohistochemistry (IHC), and its clinical value was analyzed
      using Kaplan-Meier plots and the Cox proportional hazards regression model. The
      results found that the expression levels of both PTK6 mRNA and protein in ESCC
      tissues were significantly lower than those in peritumoral normal esophageal
      tissues. Regarding the IHC analysis of ESCC, the cytoplasmic expression of PTK6
      was significantly correlated with tumor grade (P < 0.001). Compared with patients
      with low PTK6 expression, ESCC patients with overexpression of PTK6 displayed
      preferable disease-free survival (DFS) and overall survival (OS) (P < 0.001 and P
      = 0.001, respectively), especially in stage II disease (P = 0.002 and P = 0.021,
      respectively). PTK6 was evaluated as an independent prognostic factor for ESCC
      using multivariate Cox regression analysis. All data demonstrated that the
      expression level of PTK6 is an independent prognostic factor in ESCCs. Low
      expression of PTK6 is correlated with poor DFS and OS in ESCCs.

PMID- 25377661
TI  - A prognostic model based on pretreatment platelet lymphocyte ratio for stage
      IE/IIE upper aerodigestive tract extranodal NK/T cell lymphoma, nasal type.
AB  - Patients with stage IE/IIE natural killer T (NK/T) cell lymphomas have discrepant
      survival outcome. This study aims to establish a prognostic model based on the
      pretreatment platelet lymphocyte ratio (PLR) specifically for localized
      extranodal NK/T cell lymphoma to guide the therapy. We retrospectively analyzed
      the data of 252 patients with early-stage upper aerodigestive tract NK/T cell
      lymphoma. The 5-year overall survival rate in 252 patients was 67.1%. Prognostic
      factors for survival were female (P = 0.025; relative risk, 0.51; 95% CI 0.28
      0.92), older age (P = 0.000; relative risk, 3.34; 95% CI 1.94-5.75), stage II(P =
      0.020; relative risk, 1.79; 95% CI 1.10-2.91), lactate dehydrogenase (LDH) level
      (P = 0.009; relative risk, 2.00; 95% CI 1.19-3.35), and PLR (P = 0.020; relative
      risk, 1.77; 95% CI 1.10-2.87). Based on these five parameters, we identified
      three different risk groups: group 1(106 cases, 43.4%), no or one adverse factor;
      group 2(85 cases, 34.8%), two factors; group 3(53 cases, 21.7%), three to five
      factors. Five-year overall survival was 83.3% for group 1, 62.2% for group 2, and
      43.1% for group 3 (P = 0.000). Compared with International Prognostic Index and
      Korean Prognostic Index, the new model has a better prognostic discrimination for
      the patients of stage IE/IIE upper aerodigestive tract NK/T cell lymphoma. The
      PLR-based prognosis model is useful to stratify patients with localized
      extranodal NK/T cell lymphoma into different risk groups and guide the treatment
      modalities selection.

PMID- 25377662
TI  - The significant effect of heterojunction quality on photoelectrochemical water
      splitting in bilayer photoelectrodes: Rb(x)WO3 thin films on RbLaNb2O7 layers.
AB  - We have prepared nearly perfect hexagonal m-plane-oriented RbxWO3 films on (010)
      oriented RbLaNb2O7 layers. The prepared bilayer films showed Rb diffusion from
      the RbLaNb2O7 seed layers, and we obtained uniaxially oriented RbxWO3/Rb1
      yLaNb2O7 photoanodes. The RbxWO3/Rb1-yLaNb2O7 bilayer photoanodes exhibited
      enhanced photoelectrochemical water splitting compared with the RbxWO3 and
      RbLaNb2O7 monolayer photoanodes. Furthermore, we clearly demonstrated that the
      high crystal quality of the heterojunction significantly enhanced water
      splitting. The photocurrent density of the nearly perfectly oriented RbxWO3/Rb1
      yLaNb2O7 photoanode that we prepared was 9.4-fold that of an unoriented bilayer
      photoanode. This increase was attributed to the inhibition of photo-excited
      charge recombination and stimulated electron transfer derived from low grain
      boundary resistance. 

PMID- 25377663
TI  - Protective role of Klotho on cardiomyocytes upon hypoxia/reoxygenation via
      downregulation of Akt and FOXO1 phosphorylation.
AB  - Klotho is a novel anti-aging hormone involved in human coronary artery disease.
      The present study aimed to detect the effects and mechanism of Klotho on
      cardiomyocytes in a hypoxia/reoxygenation (H/R) model in vitro. Neonatal Sprague
      Dawley rat cardiomyocytes were randomly distributed into experimental groups as
      follows: Control group; H/R group, 4-h hypoxia followed by 3-h reoxygenation; and
      H/R+Klotho group, incubated with 0.1, 0.2 or 0.4 ug/ml Klotho protein for 16 h
      and then subjected to 4-h hypoxia/3-h reoxygenation. In order to evaluate
      cardiomyocyte damage, cell viability and lactate dehydrogenase (LDH) levels were
      measured. Cell apoptosis was measured by flow cytometry. The 2',7'
      dichlorofluorescein diacetate reagent was used to estimate the intracellular
      generation of reactive oxygen species (ROS). Immunofluorescence staining was used
      to test whether Klotho induced decreased nuclear translocation of forkhead box
      protein O1 (FOXO1). Western blot analysis was performed to detect protein levels
      of FOXO1, phospho-FOXO1, Akt, phospho-Akt and superoxide dismutase 2 (SOD2). Cell
      viability was significantly decreased, levels of LDH in the cardiomyocyte culture
      medium were significantly increased and the apoptotic rate was enhanced in the
      H/R group when compared with those of the control group. Compared with the H/R
      group, cell viability of the H/R+Klotho groups was significantly higher (P<0.05).
      Treatment with Klotho protein resulted in a significant resistance of
      cardiomyocytes to apoptosis and the release of LDH was decreased. Intracellular
      ROS levels in the H/R group were significantly elevated above those of the
      control group (P<0.05). Following treatment with Klotho, intracellular ROS levels
      were significantly decreased compared with those of the H/R group (P<0.05).
      Western blot analysis confirmed that Klotho protein treatment increased FOXO1
      levels in the nucleus and decreased FOXO1 levels in the cytoplasm. Furthermore,
      exogenous Klotho protein promoted translocation of FOXO1 from cytoplasm to
      nucleus. In addition, the administration of Klotho protein suppressed
      phosphorylation of FOXO1 and Akt, and markedly increased the protein expression
      levels of SOD2. In conclusion, treatment with Klotho protein had beneficial
      effects on cardiomyocytes undergoing H/R injury. The mechanism of this effect may
      be associated with suppressed apoptosis of cardiomyocytes, inhibition of
      phosphorylation of FOXO1 and Akt as well as suppression of cytoplasm transfer of
      FOXO1.

PMID- 25377664
TI  - Avoiding pitfalls in L1-regularised inference of gene networks.
AB  - Statistical regularisation methods such as LASSO and related L1 regularised
      regression methods are commonly used to construct models of gene regulatory
      networks. Although they can theoretically infer the correct network structure,
      they have been shown in practice to make errors, i.e. leave out existing links
      and include non-existing links. We show that L1 regularisation methods typically
      produce a poor network model when the analysed data are ill-conditioned, i.e. the
      gene expression data matrix has a high condition number, even if it contains
      enough information for correct network inference. However, the correct structure
      of network models can be obtained for informative data, data with such a signal
      to noise ratio that existing links can be proven to exist, when these methods
      fail, by using least-squares regression and setting small parameters to zero, or
      by using robust network inference, a recent method taking the intersection of all
      non-rejectable models. Since available experimental data sets are generally ill
      conditioned, we recommend to check the condition number of the data matrix to
      avoid this pitfall of L1 regularised inference, and to also consider alternative
      methods. 

PMID- 25377665
TI  - Food allergy, a summary of eight cases in the UK criminal and civil courts:
      effective last resort for vulnerable consumers?
AB  - Food allergy has a forensic context. The authors describe eight cases in the UK
      courts involving fatalities, personal injury or criminal non-compliance with food
      law from mainly 'grey' literature sources. The potentially severe consequences
      for people with food allergy of contraventions of labelling law have led to
      enforcement action up to criminal prosecution for what might otherwise be
      regarded as 'trivial' non-compliance. The authors suggest there should be central
      collation of such cases. Non-compliances should be followed up in a more rapid
      and robust manner. Evidence of fraud in the catering supply chain supports recent
      calls for zero tolerance of food fraud. Businesses must guard against gaps in
      allergen management, for which there are readily available sources of training
      and guidance, but also against fraudulent substitution in the supply chain, about
      which training and guidance should be developed. New allergen labelling
      legislation and case law appear to place responsibility on food businesses even
      for the forensically problematic area of allergen cross-contamination. The courts
      can be an effective last resort for vulnerable consumers; however, there is
      evidence of knowledge and skill gaps in both the investigation and prosecution of
      potentially serious incidents of food allergen mismanagement and mislabelling.
      Thorough investigation of food allergy deaths is required with a tenacious and
      skilled approach, including early realisation that samples of the food and/or
      stomach contents from a post mortem examination should be retained and analysed.
      The supply chain must be rigorously examined to find out where adulteration or
      contamination with the fatal allergen occurred.

PMID- 25377666
TI  - Resolute efforts to cure hepatitis C: Understanding patients' reasons for
      completing antiviral treatment.
AB  - Antiviral treatment for hepatitis C is usually difficult, demanding, and
      debilitating and has long offered modest prospects of successful cure. Most
      people who may need treatment have faced stigma of an illness associated with
      drug and alcohol misuse and thus may be deemed poor candidates for treatment,
      while completing a course of treatment typically calls for resolve and
      responsibility. Patients' efforts and their reasons for completing treatment have
      received scant attention in hepatitis C clinical policy discourse that instead
      focuses on problems of adherence and patients' expected failures. Thus, we
      conducted qualitative interviews with patients who had recently undertaken
      treatment to explore their reasons for completing antiviral treatment. Analysis
      of their narrative accounts identified four principal reasons: cure the
      infection, avoid a bad end, demonstrate the virtue of perseverance through a
      personal trial, and achieve personal rehabilitation. Their reasons reflect moral
      rationales that mark the social discredit ascribed to the infection and may
      represent efforts to restore creditable social membership. Their reasons may also
      reflect the selection processes that render some of the infected as good
      candidates for treatment, while excluding others. Explication of the moral
      context of treatment may identify opportunities to support patients' efforts in
      completing treatment, as well as illuminate the choices people with hepatitis C
      make about engaging in care. 

PMID- 25377667
TI  - The inherent tensions and ambiguities of hope: towards a post-formal analysis of
      experiences of advanced-cancer patients.
AB  - Sociological and anthropological analyses of hope in health-care contexts have
      tended to address institutional processes, especially the power dynamics that
      function through such systems or political economies of hope, which in turn shape
      interactions through which hopes are managed. This article extends this approach
      through a more detailed consideration of the experience of hoping itself. Our
      post-formal analysis denotes the tensions that are intrinsic and defining
      features of lifeworlds around hope, emphasising the dissonance and fragility of
      hoping. Drawing upon interview and observational data involving patients with
      advanced-cancer diagnoses who were taking part in clinical trials, we explore
      three main tensions which emerged within the analysis: tensions involving time
      and liminality between future and present; ontological tensions involving the
      concrete and the possible, the 'realistic' and the positive; and tensions in
      taken-for-grantedness between the reflective and the mundane, the specific and
      the ambiguous. Rather than three separate sets of tensions, those involving time,
      ontology and taken-for-grantedness are very much interwoven. In denoting the
      influence of social processes in engendering tensions, we bridge sociological and
      anthropological approaches with a more definition-oriented literature, developing
      understandings of hoping and its key characteristics in relation to other
      processes of coping amidst vulnerability and uncertainty. 

PMID- 25377668
TI  - [The focal infection encountered in the practical work of an
      otorhinolaryngologist].

PMID- 25377669
TI  - [The influence of the tracheal stents on the microbiocenoses of the larynx and
      trachea at different duration of the cannula-bearing period].
AB  - The objective of the present work was the microbiological analysis of laryngeal
      and tracheal mucosal swabs as well as the study of the contents of the
      tracheostomy tubes taken from the patients presenting with laryngeal and tracheal
      stenosis of different etiology. Both the in- and outpatients with different
      duration of the cannula-bearing period were involved. Special attention was given
      to the influence of the tracheal stents and the frequency of their cleaning on
      the microbiocenoses of the larynx and trachea. The study has demonstrated that
      the patients bearing cannulas are in need of everyday toilet of the tracheostomy
      tube and tracheostoma; also needed is the choice of the tubes with due regard for
      a the anatomical features along with general and local antibacterial therapy for
      reducing pathogenicity of microflora in the tracheobronchial tree and decreasing
      the frequency of postoperative complications. 

PMID- 25377670
TI  - [The morphofunctional state of the polypous tissue under conditions of
      radiofrequency-wave and laser interstitial thermal therapy].
AB  - The objective of the present work was to evaluate the morphofunctional state of
      the polypous tissue under conditions of radiofrequency-wave (from 15 to 40 W) and
      laser interstitial (from 1 to 10 W) thermal therapy. It was shown that both
      techniques exerted no influence on the structure and physiology of epithelial
      glands, regardless of the regime chosen for their application. The therapeutic
      effect was achieved due to the influence of radiation on the loose connective
      tissue leading to the modification of its structure and the reduction of the
      volume of the polypous tissue. Laser interstitial thermal therapy at 3-7 W was
      found to be the most efficacious and injurious regime. In contrast, laser
      radiation over 7 W and radiofrequency-wave treatment (15-40 W) proved the most
      traumatic regimes. They cause coagulation and tissue necrosis at the sites of
      their direct application; these effects were strongly dependent on the radiation
      power. 

PMID- 25377672
TI  - [The threshold levels of the stapedius reflex depending on the relationship
      between the gas pressure in the external auditory meatus and the middle ear].
AB  - The objective of the present work was to detect and elucidate effects of a single
      factor (gas pressure) responsible for the threshold levels of stapedius reflex.
      It was shown that the threshold reflexes were recorded at 105 dB SPL when the gas
      pressure in the external auditory meatus decreased by 150-200 pPa against the
      atmospheric pressure and when it increased by 100-150 pPa. These effects can be
      accounted for by the reduced compliance of the tympanic membrane and different
      changes in the state of the auditory ossicles undergoing compression and tension.
      When entering the most comfortable stapedial reflex levels into the patient's
      tuning chart, an account should be taken of the maximum value of tympanic
      membrane compliance. 

PMID- 25377671
TI  - [Hyposensitizing and antioxidative pharmacotherapy of the cyst-like structures in
      the maxillary sinuses].

PMID- 25377673
TI  - [The effectiveness of the auditory training of the subjects presenting with
      partial deafness following cochlear implantation as reported by the patients and
      speech therapists].
AB  - INTRODUCTION: Auditory training consists of the exercises taking advantage of the
      environmental sounds and human speech; it is designed to ensure hearing for a
      person suffering its impairment within the range of acoustic experiences
      comparable with that of the normally hearing subjects. The successful treatment
      of partial deafness with the use of a cochlear implant (CI) resulted in the
      increase of the number of patients who needed auditory training to enable them to
      recognize mid-and high-frequency sounds. Bearing in mind the lack of the teaching
      aids permitting to adequately address the specific hearing problems in such
      patients, the Rehabilitation Clinic of the Institute of Physiology and Pathology
      of Hearing undertook to develop the relevant materials to satisfy the needs of
      auditory training following surgical cochlear implantation. AIM: The evaluation,
      by the patients suffering partial deafness and speech therapists, of the
      usefulness and the difficulty of the proposed auditory training based on the use
      of environmental sounds and human speech in the mid- and high-frequency ranges.
      MATERIALS AND METHODS: The study included 29 adult CI users presenting with
      partial deafness participating in the Institute's rehabilitation program. Both
      the patients and the speech therapists independently evaluated the usefulness of
      the proposed training and the difficulties encountered with its practical
      realization by completing the questionnaire according to the Likert 5-point
      scale. RESULTS: The patients with partial deafness and speech therapists found
      out that the proposed auditory training was difficult to perform; this inference
      was especially true as regards the exercises designed to enable the
      identification of the mid- and high frequency speech sounds. The women
      experienced significantly more difficulties than men when performing the proposed
      exercises. Both the patients and the speech therapists confirmed the usefulness
      of the recommended auditory training as a component of the rehabilitation
      process. CONCLUSION: The surgical treatment of the patients presenting with
      partial deafness should be supplemented by the appropriate auditory training
      focused on the reception and identification of mid- and high-frequency sounds.
      The present study provided the rationale for the development of the materials to
      be used for rehabilitation of the subjects suffering partial deafness.

PMID- 25377674
TI  - [The clinical and functional evaluation of the combined treatment of vasomotor
      rhinitis in the children].
AB  - The objective of the present work was the comparative analysis of the results of
      the application of different methods for the treatment of the children presenting
      with vasomotor rhinitis. It was shown that the proposed combined approach
      including remedial therapy for the normalization of the function of the
      vegetative nervous system and the local application of fluctuating current to the
      nasal cavity mucosa has an advantage over the traditional modalities.
      Specifically, this newly developed simple and efficacious method for the combined
      conservative treatment of vasomotor rhinitis in the children has practically no
      contraindications for use, yields the most stable positive functional outcomes,
      and can by recommended for the application in both inpatient and outpatient
      settings to manage the patients with vasomotor rhinitis. 

PMID- 25377675
TI  - [Specific clinical and immunological features of chronic diseases of the nasal
      associated lymphoid tissue in the children].
AB  - The objective of the present work was to study the structure, clinical, and
      immunological features of various etiological variants of chronic diseases of the
      nasal-associated lymphoid tissue in the children. A total of 142 children at the
      age from 3 to 7 years presenting with this pathological condition were available
      for the observation. The study revealed differences in the clinical course of the
      disease and the cytokine response (IL-6, Ril-6, TNF, sYNFR55, sTNFR75) at the
      local and systemic levels for different pathogens (S. aureus, S. pneumoniae, S.
      pyrogenes). 

PMID- 25377676
TI  - [The morphofunctional prerequisites for the development of exudative otitis media
      in the children presenting with chronic adenoiditis].
AB  - The objective of the present study was to elucidate the structural and functional
      mechanisms underlying disturbances of the protective nasolaryngeal barrier with
      special reference to the following histological and immunohistochemical
      characteristics of the pharyngeal tonsils (CD4, CD20, CD68, IgA, P53, BCL2, Ki67,
      TGF-beta) in the children aged 3-6 years and presenting with complicated (n=20)
      or uncomplicated (n=20) chronic adenoiditis (CA). It was shown that adenoids of
      the patients with complicated chronic adenoiditis less frequently exhibit markers
      of active inflammation, such as hyperemia, intraepithelial infiltration, and
      hemosiderophages. Also, they have the smaller mean area of lymphoid follicles and
      the number of functional intrafollicular macrophages suggesting impaired
      immunological reactivity. Lymphoid follicles of the pharyngeal tonsils in the
      children with uncomplicated chronic adenoiditis show up enhanced density of B
      lymphocytes (CD20) and CD69-positive cells which may suggest functional tension.
      However, density of IgA-producing lymphocytes responsible for the protection of
      nasolaryngeal mucosa is identical in the patients with complicated and
      uncomplicated chronic adenoiditis. Taken together with the decreased number of T
      helpers (CG4), this finding indicates the compromised immunological response in
      the children with this pathology. It is concluded that the structural
      characteristics of pharyngeal tonsils revealed in the present study may provide a
      basis for the disturbances of congenital and adaptive immunity; moreover, they
      can serve as the predictors of complications of chronic adenoiditis. 

PMID- 25377677
TI  - [The clinical and polysomnographic characteristics of obstructive sleep apnea
      syndrome in the children].
AB  - The objective of the present work was to study peculiarities of the neurological,
      ororhinolaryngological status of the children presenting with obstructive sleep
      apnea syndrome (OSAS) as well as their clinical and polysomnographic (PSG) sleep
      characteristics. A total of 15 children at the age from 6 to 9 years with OSAS
      confirmed by the PSG study were included in the investigation. All the children
      suffered nasal obstruction of different etiology and non-specific neurological
      complaints of transient headache, emotional lability, impaired memory, enhanced
      fatigue, and poor attention; these conditions were responsible for school
      desadaptation. All the patients underwent dyssomnic events. The polysomnographic
      study revealed the disordered sleep structure manifested as the shortened
      drowsiness phase, lengthened latent period of the rapid eye movement (REM) sleep
      and its reduced representation in the overall sleep cycle, enhanced duration of
      delta-sleep. The sleep alertness time also increased alongside with a rise in the
      number of activations on the sleep electroencephalograms by virtue of increased
      respiratory efforts. A characteristic feature of the children presenting with
      obstructive sleep apnea syndrome was vegetative disorder during sleep associated
      with a rise in the number of tachycardia episodes. The results of this study
      facilitate the understanding of certain pathogenetic aspects of neurological
      problems in the children suffering respiratory tract obstruction and OSAS and
      outline the problems awaiting further investigations. 

PMID- 25377678
TI  - [The influence of hormonal therapy on the development of rhinitis in the pregnant
      women].
AB  - The objective of the present study was to evaluate the influence of hormonal
      therapy used to correct the hormonal status of the pregnant women during
      different periods of gestation on the development of the nasal obstruction
      symptoms. A total of 53 case histories of the pregnant women (urban residents)
      were available for the analysis. In 2012, all the patients were under observation
      of an obstetrician-gyneciologist based at an outpatient setting. 16 of them
      (30.2%) suffered stuffness in the nose that was especially well pronounced during
      the II and III trimesters (37.5% in each trimester). Mild stuffness predominated
      over the moderate and strong ones (62.5, 18.75 and 18.75% respectively). The
      disturbed hormonal status was documented in 13 (81.75%) pregnant women in the
      form of reduced progesterone and human CG-beta levels and increased serum DHEA-C
      concentration. The hormonal status was corrected during the I and II trimesters.
      The women having very high serum DHEA-C concentration were treated with metypred;
      those with the low progesterone level were given utrogestan. In both groups, the
      diseases was especially well manifested in the early II trimester. It is
      conjectured that therapy with the use of progesterone and glucocorticoid-based
      preparations had no appreciable effect on the development of rhinitis in the
      pregnant women. 

PMID- 25377679
TI  - [The experimentally-based rationale for the application of the new methods
      designed to treat fungal adenoiditis in the children].
AB  - The objective of the present was to evaluate the influence of local anesthetics
      protargol, miramistin, chlorohexidine, and photodynamic therapy (PDT) on the
      polyresistant strain of Candida tropicalis isolated from a sick child presenting
      with fungal adenoiditis. In vitro experiments were designed to estimate the
      inactivation potential of the Candida tropicalis blastospore suspension (5.107
      CFU/ml) following the preliminary incubation with a 5 mcmol/l methylene blue
      solution. A Kreolka FDT apparatus operated at the 680 nm wavelength was employed
      as the source of radiation in a broad power and time ranges. Simultaneously,
      experiments were carried out to determine the minimum concentration of the
      protargol, miramistin, and chlorohexidine solutions inhibiting the growth of the
      same fungal strain. The minimum growth inhibitory concentrations of these
      solutions were found to be 0.1%, 0.005%, and 0.005% respectively. The
      photodynamic therapy using the minimal inhibitory dose of 150 J with a 5 min
      exposition and an output power of 0.5 W completely suppressed the growth of the
      Candida tropicalis colonies in the presence of methylene blue as the
      photosensitizer.

PMID- 25377680
TI  - [The giant osteoma of the mastoid process of the temporal bone].

PMID- 25377681
TI  - [The transtympanic administration of steroids for the treatment of acute
      sensorineural hearing impairment].
AB  - The objective of the present study was to compare the effectiveness of two
      methods (transtympanic and intravenous) administration of steroids and standard
      therapy for the treatment of the patients presenting with acute sensorineural
      hearing impairment (OSNHI). MATERIALS AND METHODS: The study included 56 patients
      with this pathology. 18 of them were given transtympanic injections of steroids;
      10 others received steroids intravenously in the combination with standard
      therapy. 28 patients were treated by the standard therapy alone. The
      effectiveness of the treatment was estimated by means of tonal threshold
      audiometry. RESULTS: None of the patients in the first group enjoined total
      normalization of hearing. Its improvement by 10-29 dB was documented in 22
      (78.6%) patients. In the second group hearing improved by 15-20 dB in 4 (40%) and
      by 5-10 dB in 6 (60%) patients. In the third group, 14 (77.7%) patients reported
      improvement of hearing and reduced noise as early as the first puncture. By the
      time of discharge from the hospital, their hearing improved by 30-40 dB while the
      15-20 dB improvement was documented in 2 (11.1%) patients and the 5-10 dB
      improvement in another 2 (11.1%) patients. The study has demonstrated the high
      effectiveness of glucocorticoid therapy especially in the case of transtympanic
      administration of these steroids.

PMID- 25377682
TI  - [Diagnosis and treatment of allergic rhinitis aggravated by respiratory tract
      infection].
AB  - The objective of the present paper was to propose an optimal scope of diagnostic
      studies for the patients complaining of rhinitis symptoms for the early detection
      of allergic rhinitis, including a differential diagnosis with associated
      respiratory tract infections. A comprehensive treatment is offered including the
      use of vasoconstrictors and antihistamines, eliminationand
      immunocorrectivetherapy with Ribomunyl. 

PMID- 25377683
TI  - [Comparative effectiveness of preparations for cerumenolysis].

PMID- 25377684
TI  - [The problems of education in otosurgery: the current state-of-the-art].
AB  - An overview of the current problems of education in ear surgery is presented. The
      methods used for the purpose including the classical dissection of the temporal
      bone, application of synthetic and natural (animal) temporal bones are described
      alongside with the 3D models of the temporal bone and virtual dissection. In
      addition, the review covers the problem of enhancing effectiveness of the
      teaching methods, considers their advantages and disadvantages. 

PMID- 25377685
TI  - [The concept of the development of the otorhinolaryngological service in Moscow
      under conditions of modernization of the healthcare system and single-channel
      funding].
AB  - This paper highlights the complex of organizational and socio-economic measures
      designed to modify the healthcare system in the city of Moscow, improve the
      quality of medical aid, and ensure its availability for the urban population. The
      proposed methods were developed based on the results of analysis of the data
      obtained in the course of checking the work of the otorhinolaryngological
      services of the city, analysis of effectiveness of using the hospital stock in
      the therapeutic and prophylactic facilities of Moscow. 

PMID- 25377686
TI  - Mesoporosity changes from cambium to mature tension wood: a new step toward the
      understanding of maturation stress generation in trees.
AB  - In order to progress in the understanding of mechanical stress generation, the
      mesoporosity of the cell wall and its changes during maturation of poplar
      (Populus deltoides * P. nigra) tension wood (TW) and opposite wood (OW) were
      measured by nitrogen adsorption-desorption. Variations in the thickness of the
      gelatinous layer (G-layer) were also measured to clarify whether the mesoporosity
      change simultaneously with the deposition of the G-layer in TW. Results show that
      mesoporous structures of TW and OW were very similar in early development stages
      before the deposition of G-layers. With the formation of the S2 layer in OW and
      the G-layer in TW, the mesopore volume decreased steeply before lignification.
      However, in TW only, the decrease in mesopore volume occurred together with the
      pore shape change and a progressive increase in pore size. The different patterns
      observed in TW revealed that pores from G-layers appear with a different shape
      compared to those of the compound middle lamella, and their size increases during
      the maturation process until stabilising in mature wood. This observation
      strongly supports the hypothesis of the swelling of the G-layer matrix during
      maturation as the origin of maturation stress in poplar tension wood.

PMID- 25377687
TI  - New combination bronchodilators for chronic obstructive pulmonary disease:
      current evidence and future perspectives.
AB  - Fixed dose combination (FDC) dual bronchodilators that co-administer a long
      acting beta2 -adrenoceptor agonist (LABA) and a long acting muscarinic antagonist
      (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary
      disease (COPD). This review focuses on the clinical evidence for the benefit of
      LABA/LAMA FDCs compared with monocomponent treatments, and also compared with
      active comparators that are widely used for the treatment of COPD, namely
      tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include
      QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that
      QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough
      forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited
      to approximately 80-90% of the added monocomponent values. This suggests that the
      effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were
      associated with the largest mean changes in symptoms and health status that were
      above the minimal clinically important difference, in contrast to the
      monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over
      the active comparators tiotropium and salmeterol-fluticasone in terms of trough
      FEV1 and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of
      maximizing bronchodilation for COPD patients, with the improvements in lung
      function being mirrored by benefits in terms of symptoms and exacerbations. The
      use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are
      needed to define their optimal place in treatment guidelines.

PMID- 25377688
TI  - Myocardial fat overgrowth in Proteus syndrome.
AB  - Proteus syndrome (PS) is a rare, mosaic disorder with asymmetric and distorting
      overgrowth of the skeletal system, skin, and adipose tissues. Cardiac
      abnormalities are rare in this syndrome and only two prior cases have been
      reported. Many patients with PS followed at our institution underwent
      transthoracic echocardiograms for preoperative evaluation or as work-up for
      associated pulmonary disease. Some were noted to have prominent, focal echodense
      areas in the myocardium. We further investigated cardiac findings in a cohort of
      children and adult patients with PS. Patients with abnormal echocardiograms were
      referred for cardiac magnetic resonance imaging, Holter monitoring, and exercise
      treadmill testing. Twenty children and adults with PS, age 24 months to 50 years
      old, underwent transthoracic echocardiograms. Seven patients (35%) had focal
      bright echodense areas within the myocardium suggesting fatty infiltration. The
      majority of patients had significant involvement of the interventricular septum.
      The cardiac characteristics of all patients with fatty infiltration on
      transthoracic echocardiograms were compared to Proteus patients without these
      findings. There were no significant differences in chamber sizes, mass, systolic
      or diastolic function. No increased risk of conduction defects or arrhythmias was
      found. This study shows that abnormal fat overgrowth is a common finding in the
      myocardium in patients with Proteus syndrome; however, it is not associated with
      functional derangements or arrhythmias. Further evaluation of a larger number of
      Proteus patients is needed in order to determine the frequency and prognosis of
      cardiac involvement. Published 2014. This article is a U.S. Government work and
      is in the public domain in the USA. 

PMID- 25377689
TI  - The rise in metastasectomy across cancer types over the past decade.
AB  - BACKGROUND: Although studies of metastasectomy have been limited primarily to
      institutional experiences, reports of favorable long-term outcomes have generated
      increasing interest. In the current study, the authors attempted to define the
      national practice patterns in metastasectomy for 4 common malignancies with
      varying responsiveness to systemic therapy. METHODS: The National (Nationwide)
      Inpatient Sample was used to estimate the national incidence of metastasectomy
      for colorectal cancer, lung cancer, breast cancer, and melanoma from 2000 through
      2011. Incidence-adjusted rates were determined for liver, lung, brain, small
      bowel, and adrenal metastasectomies. The average annual percentage change (AAPC)
      in metastasectomy by cancer type was calculated using joinpoint regression.
      RESULTS: Colorectal cancer was the most common indication for metastasectomy
      (87,407 cases; 95% confidence interval [95% CI], 86,307-88,507 cases) followed by
      lung cancer (58,245 cases; 95% CI, 57,453-59,036 cases), breast cancer (26,271
      cases; 95% CI, 25,672-26,870 cases), and melanoma (20,298 cases; 95% CI, 19,897
      20,699 cases). Metastasectomy increased significantly for all cancer types over
      the study period: colorectal cancer (AAPC, 6.83; 95% CI, 5.7-7.9), lung cancer
      (AAPC, 5.8; 95% CI, 5.1-6.4), breast cancer (AAPC, 5.5; 95% CI, 3.7-7.3), and
      melanoma (AAPC, 4.03; 95% CI, 2.1-6.0). Despite an increasing number of
      comorbidities in patients undergoing metastasectomy (P<.05 for each cancer type),
      inpatient mortality rates after metastasectomy fell for all cancer types, most
      significantly for colorectal (AAPC, -5.49; 95% CI, -8.2 to -2.7) and lung (AAPC, 
      6.2; 95% CI, -11.7 to -0.3) cancers. The increasing performance of metastasectomy
      was largely driven by high-volume institutions, in which patients had a lower
      mean number of comorbidities (P<.01 for all cancer types) and lower inpatient
      mortality (P<.01 for all cancers except melanoma). CONCLUSIONS: From 2000 through
      2011, the performance of metastasectomy increased substantially across common
      cancer types, notwithstanding various advances in systemic therapies.
      Metastasectomy was performed more safely, despite increasing patient comorbidity.
      High-volume institutions appeared to drive practice patterns.

PMID- 25377690
TI  - Toward a comprehensive model of ?(9)-tetrahydrocannabinol pharmacokinetics using
      a population pharmacokinetics approach.

PMID- 25377692
TI  - Acute and Chronic Erysipelothrix rhusiopathiae Infection in Lambs.
AB  - Polyarthritis caused by Erysipelothrix rhusiopathiae is a relatively common
      infection in lambs characterized by low mortality and high morbidity. E.
      rhusiopathiae is a ubiquitous Gram-positive bacterium that is both a commensal
      and a pathogen of vertebrates. The disease was studied during an outbreak in a
      Norwegian Spael sheep flock. In the acute phase, 48 of 230 (20%) lambs developed
      clinical signs and 4 died (1.7%). One acute case was necropsied and E.
      rhusiopathiae was cultured from all major organs investigated and from joints.
      There was a fibrinous polyarthritis, increased presence of monocytes in vessels,
      and necrosis of Purkinje cells. Sixteen of the diseased animals (33%) developed a
      chronic polyarthritis. Eight of these lambs were necropsied; all had lesions in
      major limb joints, and 3 of 8 also had lesions in the atlanto-occipital joint. At
      this stage, E. rhusiopathiae was cultured only from the joints in 7 of 8 (87.5%)
      lambs, but by real-time polymerase chain reaction, we showed persistence of the
      bacterium in several organs. Pulsed-field gel electrophoresis typing of the
      bacterial isolates indicated that the same strain caused the acute and chronic
      disease. Five of 6 (83%) chronically affected animals had amyloidosis of the
      spleen, and 6 of 8 (75%) had amyloidosis of the liver. All chronically affected
      animals had a glomerulonephritis, and 6 of 8 (75%) had sparse degeneration in the
      brain. Ceruloplasmin and haptoglobin were significantly increased in the
      chronically diseased lambs. These results show that chronic ovine erysipelas is
      not restricted to joints but is a multisystemic disease. 

PMID- 25377693
TI  - Pathologic and Environmental Studies Provide New Pathogenetic Insights Into
      Ringtail of Laboratory Mice.
AB  - Ringtail is a pathologic condition of laboratory rodents characterized by annular
      constrictions of the tail. Traditionally, it is classified as an environmental
      disorder caused by low relative humidity, but other factors (temperature, dietary
      deficiencies, genetic susceptibility, and caging type) have also been proposed.
      Twenty litters of mice with ringtail lesions occurred from September 2010 to
      August 2013 in a facility located in the northern Italy. Mice were maintained
      under controlled environmental conditions and fed a standard diet. Retrospective
      analysis of environmental data (relative humidity, temperature) was carried out.
      Gross, histopathologic, scanning, and transmission electron microscopy
      examination of tails and limbs was performed. The incidence of ringtail was
      0.075% (20/26 800) of all weaned litters over the 3-year period of examination.
      Temperature and relative humidity remained within accepted limits in all cases
      except one. We observed annular constrictions in tail, digits of pes, crus, and
      antebrachium in 116 (100.0%), 47 (40.5%), 11 (9.5%), and 2 (1.7%) of 116 affected
      mice, respectively. Histologic and ultrastructural examination revealed abnormal
      keratin desquamation and presence of a keratin ring encircling the tail, causing
      progressive strangulation of the growing tail with subsequent compression and
      ulceration of underlying soft tissues, resulting in circulatory changes (edema,
      hyperemia, thrombosis, hemorrhages), ischemic necrosis, and eventually auto
      amputation distal to the constriction. On the basis of our findings, we suggest a
      disorder of cornification as the primary lesion of ringtail in mice. The cause of
      these cases, however, remained undetermined, even though traditional etiologic
      factors (relative humidity, temperature, diet, caging type) were reasonably
      excluded. 

PMID- 25377695
TI  - The relationship between R-wave magnitude and ventricular volume during
      continuous left ventricular assist device assistance: experimental study.
AB  - The current use of left ventricular assist devices (LVADs) as destination therapy
      is associated with the clinical need of monitoring patient-pump interaction. To
      this aim, the present work investigated the possibility of getting useful
      information about the status of the assisted left ventricle using
      electrocardiographic (ECG) data. A total of six animals, undergoing Gyro
      Centrifugal Pump 2 implantation (a new version of Gyro Centrifugal Pump C1E3
      [Kyocera Corporation, Kyoto, Japan]) and CircuLite Synergy Micropump (CircuLite,
      Inc., Saddlebrooke, NJ, USA) in atrio-aortic connection, were analyzed. Data
      refer to different LVAD speeds with consequently different levels of ventricular
      unloading. From ECG signal, the R wave peak was individuated together with the
      corresponding left ventricular volume. Then on both signals, a moving average
      analysis was performed to reduce the effect of the ventilation. A regression and
      correlation analysis performed on the two resulting signals evidenced that the R
      wave peak and the ventricular volume are strictly related. Specifically, any
      change of LVAD speed, inducing a change in ventricular volume, is associated with
      a change in R wave peak value. The present work is a first step in investigating
      the usefulness of the ECG signal during LVAD therapy, for the monitoring of
      mechanical parameters of the heart such as the ventricular volumes. The
      correlation found between the ECG and the ventricular volume can be a promising
      starting point for possible future noninvasive LVAD patient monitoring. 

PMID- 25377694
TI  - Critical role of the right uncinate fasciculus in emotional empathy.
AB  - OBJECTIVE: Common neurological diseases or injuries that can affect the right
      hemisphere, including stroke, traumatic brain injury, and frontotemporal
      dementia, disrupt emotional empathy-the ability to share in and make inferences
      about how other people feel. This impairment negatively impacts social
      interactions and relationships. Accumulating evidence indicates that emotional
      empathy depends on coordinated functions of orbitofrontal cortex, anterior
      insula, anterior cingulate, temporal pole, and amygdala, but few studies have
      investigated effects of lesions to white matter tracts that connect these
      structures. We tested the hypothesis that percentage damage to specific white
      matter tracts connecting these gray matter structures predicts error rate in an
      emotional empathy task after acute right hemisphere ischemic stroke. METHODS: We
      used multivariate linear regression with percentage damage to 8 white matter
      tracts, age, and education as independent variables and error rate on emotional
      empathy as the dependent variable to test a predictive model of emotional empathy
      in 30 patients with acute ischemic right hemisphere stroke. RESULTS: Percentage
      damage to 8 white matter tracts along with age and education predicted the error
      rate in emotional empathy, but only percentage damage to the uncinate fasciculus
      was independently associated with error rate. Participants with right uncinate
      fasciculus lesions were significantly more impaired than right hemisphere stroke
      patients without uncinate fasciculus lesions in the emotional empathy task.
      INTERPRETATION: The right uncinate fasciculus plays an important role in the
      emotional empathy network. Patients with lesions in this network should be
      evaluated for empathy, so that deficits can be addressed.

PMID- 25377691
TI  - Nanomedical engineering: shaping future nanomedicines.
AB  - Preclinical research in the field of nanomedicine continues to produce a steady
      stream of new nanoparticles with unique capabilities and complex properties. With
      improvements come promising treatments for diseases, with the ultimate goal of
      clinical translation and better patient outcomes compared with current standards
      of care. Here, we outline engineering considerations for nanomedicines, with
      respect to design criteria, targeting, and stimuli-triggered drug release
      strategies. General properties, clinical relevance, and current research advances
      of various nanomedicines are discussed in light of how these will realize their
      potential and shape the future of the field.

PMID- 25377696
TI  - Draft Genome Sequence of Chromobacterium haemolyticum Causing Human Bacteremia
      Infection in Japan.
AB  - Chromobacterium haemolyticum is a Gram-negative bacterium displaying remarkable
      hemolysis against human and sheep erythrocytes. In addition, C. haemolyticum
      infects humans, in which the infection mechanism remains unknown. We report here
      the draft genome sequence of C. haemolyticum strain T124, isolated from a young
      patient with sepsis in Japan. 

PMID- 25377697
TI  - Complete Genome Assembly of Staphylococcus epidermidis AmMS 205.
AB  - Staphylococcus epidermidis causes a large number of catheter-related sepsis
      infections annually in the United States. We present the 2.54-Mbp complete genome
      assembly of reference strain S. epidermidis AmMS 205, including a single 37.7-kbp
      plasmid. The annotated assembly is available in GenBank under accession numbers
      CP009046 and CP009047. 

PMID- 25377698
TI  - Draft Genome Sequence of Bacillus coagulans GBI-30, 6086, a Widely Used Spore
      Forming Probiotic Strain.
AB  - Bacillus coagulans GBI-30, 6086 is a safe strain, already available on the
      market, and characterized by certified beneficial effects. The draft genome
      sequence presented here constitutes the first pillar toward the identification of
      the molecular mechanisms responsible for its positive features and safety. 

PMID- 25377699
TI  - Draft Genome Sequence of Non-O1 and Non-O139 Vibrio cholerae Strain VCC19.
AB  - Vibrio cholerae O1 is the causative agent of cholera and is ubiquitous in the
      aquatic environment, while V. cholerae strains non-O1 and non-O139 are recognized
      as causative agents of sporadic and localized outbreaks of diarrhea. Here, we
      report the complete sequence of a non-O1 and non-O139 V. cholerae strain (VCC19),
      which was isolated from the environment in Brazil. The sequence includes the
      integrative conjugative element (ICE). This paper is the first report of the
      presence of such an element in a V. cholerae strain isolated in Brazil. 

PMID- 25377700
TI  - Complete genome sequence of a rat hepatitis e virus strain isolated in the United
      States.
AB  - Hepatitis E virus is a common cause of acute hepatitis in humans. Related viruses
      have been isolated from multiple animal species, including rats, but their impact
      on human health is unclear. We present the first full-length genome sequence of a
      rat hepatitis E virus strain isolated in the United States (LA-B350). 

PMID- 25377701
TI  - Complete Genome Sequence of the Quality Control Strain Staphylococcus aureus
      subsp. aureus ATCC 25923.
AB  - Staphylococcus aureus subsp. aureus ATCC 25923 is commonly used as a control
      strain for susceptibility testing to antibiotics and as a quality control strain
      for commercial products. We present the completed genome sequence for the strain,
      consisting of the chromosome and a 27.5-kb plasmid. 

PMID- 25377702
TI  - Draft Genome Sequences of Two Clostridium botulinum Group II (Nonproteolytic)
      Type B Strains (DB-2 and KAPB-3).
AB  - Clostridium botulinum is important for food safety and studies of neurotoxins
      associated with human botulism. We present the draft genome sequences of two
      strains belonging to group II type B: one collected from Pacific Ocean sediments
      (DB-2) and another obtained during a botulism outbreak (KAPB-3). 

PMID- 25377703
TI  - Draft Genome Sequence of Pseudomonas aeruginosa ATCC 33988, a Bacterium Highly
      Adapted to Fuel-Polluted Environments.
AB  - Pseudomonas aeruginosa ATCC 33988 is highly adapted to grow in jet and diesel
      fuel, with a defined regulation of adaptive genes and metabolization of n
      alkanes. The draft genome of strain ATCC 33988 is 6.4 Mb in size, with 5,975
      coding sequences and 66.3% G+C content, and it is highly similar to that of the
      clinical strain P. aeruginosa PAO1. 

PMID- 25377704
TI  - Genome Sequence of the Lactic Acid Bacterium Lactococcus lactis subsp. lactis
      TOMSC161, Isolated from a Nonscalded Curd Pressed Cheese.
AB  - Lactococcus lactis is a lactic acid bacterium used in the production of many
      fermented foods, such as dairy products. Here, we report the genome sequence of
      L. lactis subsp. lactis TOMSC161, isolated from nonscalded curd pressed cheese.
      This genome sequence provides information in relation to dairy environment
      adaptation. 

PMID- 25377705
TI  - Draft Genome Sequence of Sulfitobacter sp. CB2047, a Member of the Roseobacter
      Clade of Marine Bacteria, Isolated from an Emiliania huxleyi Bloom.
AB  - We announce the draft genome sequence of Sulfitobacter sp. strain CB2047, a
      marine bacterium of the Roseobacter clade, isolated from a phytoplankton bloom.
      The genome encodes pathways for the catabolism of aromatic compounds as well as
      transformations of carbon monoxide and sulfur species. The strain also encodes a
      prophage as well as the gene transfer agent (GTA), both of which are prevalent
      among members of the Rhodobacterales order. 

PMID- 25377706
TI  - Draft Genome Sequence of Bacillus fengqiuensis FJAT-14578, Isolated from a Soil
      Sample in China.
AB  - Here, we report the first high-quality draft genome sequence of Bacillus
      fengqiuensis FJAT-14578, isolated from a soil sample collected from China. The
      genome size was 5,569,389 bp, with a 40.93 mol% G+C content. The number of tRNAs
      was 69 and of rRNAs was 10 (5S, 16S, and 23S). 

PMID- 25377707
TI  - Draft Genome Sequence of Rhizobium sp. H41, a Rock-Weathering Bacterium from a
      Weathered Rock Surface.
AB  - Rhizobium sp. H41 isolated from weathered tuff can weather tuff and release Fe,
      Si, and Al from the rock under nutrient-poor conditions. Here, we report the
      draft genome sequence of strain H41, which may facilitate a better understanding
      of the molecular mechanism involved in rock weathering by the bacterium. 

PMID- 25377708
TI  - Draft Genome Sequence of Leuconostoc mesenteroides P45 Isolated from Pulque, a
      Traditional Mexican Alcoholic Fermented Beverage.
AB  - Leuconostoc mesenteroides P45 was isolated from the traditional Mexican pulque
      beverage. We report its draft genome sequence, assembled in 6 contigs consisting
      of 1,874,188 bp and no plasmids. Genome annotation predicted a total of 1,800
      genes, 1,687 coding sequences, 52 pseudogenes, 9 rRNAs, 51 tRNAs, 1 noncoding
      RNA, and 44 frameshifted genes. 

PMID- 25377709
TI  - Draft Genome Sequence of Lysinimicrobium mangrovi NBRC 105856T, Isolated from the
      Rhizosphere of a Mangrove.
AB  - Here, we report the draft genome sequence of the only species of the genus
      Lysinimicrobium, Lysinimicrobium mangrovi NBRC 105856(T), isolated from the
      rhizosphere of a mangrove. The first genomic sequence of this genus and species
      presented here will facilitate taxonomical, ecological, and functional studies of
      this rare actinobacterial group. 

PMID- 25377710
TI  - Metagenomics of the mucosal microbiota of European eels.
AB  - European eels are an economically important and threatened species that are prone
      to rapid collapse in farm conditions. Using metagenomics, we show that the eel
      mucosal microbiota has specific features distinguishing it from the surrounding
      aquatic community. This is a first step in dissecting the resident microbiota of
      this critical barrier that may have implications for maintenance of healthy eel
      populations. 

PMID- 25377711
TI  - Whole-Genome Sequences of Five Oligotrophic Bacteria Isolated from Deep within
      Lechuguilla Cave, New Mexico.
AB  - Here, we report the whole-genome sequences and annotation of five oligotrophic
      bacteria from two sites within the Lechuguilla Cave in the Carlsbad Caverns
      National Park, NM. Three of the five genomes contain an acyl-homoserine lactone
      signal synthase ortholog (luxI) that is involved in cell-to-cell communication
      via quorum sensing. 

PMID- 25377712
TI  - Genomic Sequence of the Yeast Kluyveromyces marxianus CCT 7735 (UFV-3), a Highly
      Lactose-Fermenting Yeast Isolated from the Brazilian Dairy Industry.
AB  - Here, we present the draft genome sequence of Kluyveromyces marxianus CCT 7735
      (UFV-3), including the eight chromosomes and the mitochondrial genomic sequences.

PMID- 25377713
TI  - Draft Genome Sequence of a Novel SAR11 Clade Species Abundant in a Tibetan Lake.
AB  - SAR11 clade bacteria are abundant and play a key role in the nutrient cycles of
      marine and, presumably, inland aquatic environments. We report here the draft
      genome sequence of a novel species in the SAR11 cluster, reconstructed from a
      metagenomic data set obtained from a Tibetan lake. 

PMID- 25377714
TI  - Complete genome sequence of an emerging genotype of tobacco streak virus in the
      United States.
AB  - We report here the complete genome sequence of an emerging genotype of tobacco
      streak virus (TSV) infecting zucchini squash in Florida (TSV_FL13-07), obtained
      using deep sequencing of short RNAs (sRNAs) and validation by Sanger sequencing.
      TSV_FL13-07 shares only <90% sequence identity in all three genomic RNAs to
      several known U.S. isolates. 

PMID- 25377715
TI  - Draft Genome Sequence of Bacillus subtilis Strain NKYL29, an Antimicrobial
      Peptide-Producing Strain from Soil.
AB  - Bacillus subtilis strain NKYL29 is an antimicrobial-peptide-producing strain
      isolated from the soil of Ranzhuang Tunnel in Hebei Province, China. Here, we
      present the draft genome of this strain, which provides the genetic basis for
      application of the antimicrobial peptide. 

PMID- 25377716
TI  - Complete Genome Sequence of Cellulophaga lytica HI1 Using PacBio Single-Molecule
      Real-Time Sequencing.
AB  - We report here the complete genome sequence of Cellulophaga lytica HI1 isolated
      from a seawater table located at the Kewalo Marine Laboratory (Honolulu, HI).
      This is the first complete de novo genome assembly of C. lytica HI1 using PacBio
      single-molecule real-time (SMRT) sequencing, which resulted in a single scaffold
      of 3.8 Mb. 

PMID- 25377717
TI  - Genome Sequence of Borrelia crocidurae Strain 03-02, a Clinical Isolate from
      Senegal.
AB  - The draft genome sequence of Borrelia crocidurae strain 03-02, a blood isolate
      from a febrile Senegalese patient, comprises a 920,021-bp linear chromosome
      (27.7% G+C content), 32 tRNAs, 818 open reading frames, and one cluster of
      regularly interspaced short palindromic repeats. Its genotype differs from that
      of the Achema reference strain. 

PMID- 25377718
TI  - Draft Genome Sequence of the Iron-Oxidizing Acidophile Leptospirillum ferriphilum
      Type Strain DSM 14647.
AB  - The genomic features of the Leptospirillum ferriphilum type strain DSM 14647 are
      described here. An analysis of the predicted genes enriches our knowledge of the
      molecular basis of iron oxidation, improves our understanding of its role in
      industrial bioleaching, and suggests how it is adapted to live at extremely low
      pH. 

PMID- 25377719
TI  - Genome Sequence of Rickettsia hoogstraalii, a Geographically Widely Distributed
      Tick-Associated Bacterium.
AB  - Rickettsia hoogstraalii is a tick-associated member of the spotted fever group
      rickettsiae that is geographically widely distributed. We report here the draft
      genome of R. hoogstraalii strain Croatica(T) (=DSM 22243 = UTMB 00003), which was
      isolated from Haemaphysalis sulcata ticks collected in Croatia. 

PMID- 25377720
TI  - A Versatile Synthetic Extracellular Matrix Mimic via Thiol-Norbornene
      Photopolymerization.
AB  - Step-growth, radically mediated thiol-norbornene photopolymerization is used to
      create versatile, stimuli-responsive poly(ethylene glycol)-co-peptide hydrogels
      The reaction is cytocompatible and allows for the encapsulation of human
      mesenchymal stem cells with a viability greater than 95%. Cellular spreading is
      dictated via three-dimensional biochemical photopatterning. 

PMID- 25377721
TI  - Understanding of how Propionibacterium acidipropionici respond to propionic acid
      stress at the level of proteomics.
AB  - Propionic acid (PA) is an important platform chemical in the food, agriculture,
      and pharmaceutical industries and is mainly biosynthesized by propionibacteria.
      Acid tolerance in PA-producing strains is crucial. In previous work, we
      investigated the acid tolerance mechanism of Propionibacterium acidipropionici at
      microenvironmental levels by analyzing physiological changes in the parental
      strain and three PA-tolerant mutants obtained by genome shuffling. However, the
      molecular mechanism of PA tolerance in P. acidipropionici remained unclear. Here,
      we performed a comparative proteomics study of P. acidipropionici CGMCC 1.2230
      and the acid-tolerant mutant P. acidipropionici WSH1105; MALDI-TOF/MS identified
      24 proteins that significantly differed between the parental and shuffled
      strains. The differentially expressed proteins were mainly categorized as key
      components of crucial biological processes and the acid stress response.
      Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used
      to confirm differential expression of nine key proteins. Overexpression of the
      secretory protein glyceraldehyde-3-phosphate dehydrogenase and ATP synthase
      subunit alpha in Escherichia coli BL21 improved PA and acetic acid tolerance;
      overexpression of NADH dehydrogenase and methylmalonyl-CoA epimerase improved PA
      tolerance. These results provide new insights into the acid tolerance of P.
      acidipropionici and will facilitate the development of PA production through
      fermentation by propionibacteria. 

PMID- 25377723
TI  - Prevalence of chronic medical conditions in Switzerland: exploring estimates
      validity by comparing complementary data sources.
AB  - BACKGROUND: Prevalence estimates of chronic medical conditions and their
      multiples (multimorbidity) in the general population are scarce and often rather
      speculative in Switzerland. Using complementary data sources, we assessed
      estimates validity of population-based prevalence rates of four common chronic
      medical conditions with high impact on cardiovascular health (diabetes mellitus,
      hypertension, dyslipidemia, obesity). METHODS: We restricted our analyses to
      patients 15-94 years old living in the German speaking part of Switzerland. Data
      sources were: Swiss Health Survey (SHS, 2007, n = 13,580); Family Medicine ICPC
      Research using Electronic Medical Record Database (FIRE, 2010-12, n = 99,441);
      and hospital discharge statistics (MEDSTAT, 2009-10, n = 883,936). We defined
      chronic medical conditions based on use of drugs, diagnoses, and measurements.
      RESULTS: After a careful harmonization of the definitions, a high degree of
      concordance, especially regarding the age- and gender-specific distribution
      patterns, was found for diabetes mellitus (defined as drug use or diagnosis in
      SHS, drug use or diagnosis or blood glucose measurement in FIRE, and ICD-10 codes
      E10-14 as secondary diagnosis in MEDSTAT) and for hypertension (defined as drug
      use alone in SHS and FIRE, and ICD-10 codes I10-15 or I67.4 as secondary
      diagnosis in MEDSTAT). A lesser degree of concordance was found for dyslipidemia
      (defined as drug use alone in SHS and FIRE, and ICD-10 code E78 in MEDSTAT), and
      for obesity (defined as BMI >= 30 kg/m(2) derived from self-reported height and
      weight in SHS, from measured height and weight or diagnosis of obesity in FIRE,
      and ICD-10 code E66 as secondary diagnosis in MEDSTAT). MEDSTAT performed well
      for clearly defined diagnoses (diabetes, hypertension), but underrepresented
      systematically more symptomatic conditions (dyslipidemia, obesity). CONCLUSION:
      Complementary data sources can provide different prevalence estimates of chronic
      medical conditions in the general population. However, common age and sex
      patterns indicate that a careful harmonization of the definition of each chronic
      medical condition permits a high degree of concordance.

PMID- 25377724
TI  - Melatonin: a "Higgs boson" in human reproduction.
AB  - As the Higgs boson could be a key to unlocking mysteries regarding our Universe,
      melatonin, a somewhat mysterious substance secreted by the pineal gland primarily
      at night, might be a crucial factor in regulating numerous processes in human
      reproduction. Melatonin is a powerful antioxidant which has an essential role in
      controlling several physiological reactions, as well as biological rhythms
      throughout human reproductive life. Melatonin, which is referred to as a hormone,
      but also as an autocoid, a chronobiotic, a hypnotic, an immunomodulator and a
      biological modifier, plays a crucial part in establishing homeostatic,
      neurohumoral balance and circadian rhythm in the body through synergic actions
      with other hormones and neuropeptides. This paper aims to analyze the effects of
      melatonin on the reproductive function, as well as to shed light on immunological
      and oncostatic properties of one of the most powerful hormones.

PMID- 25377725
TI  - Association between cervical screening and prevention of invasive cervical cancer
      in Ontario: a population-based case-control study.
AB  - OBJECTIVE: The aim of this study was to estimate the effect of cervical screening
      in the prevention of invasive cervical cancer among age groups, using a
      population-based case-control study in the province of Ontario, Canada. METHODS:
      Exposure was defined as cervical cytology history greater than 3 months before
      the diagnosis date of cervical cancer (index date). Cases were women who were
      diagnosed with cervical cancer between January 1, 1998, and December 31, 2008.
      Controls were women without a diagnosis of cervical cancer on, or before,
      December 31, 2008. Two controls were matched to each case on year of birth and
      income quintile, as of the index date. Conditional logistic regression was used
      to estimate the odds ratio for having been screened among those with cervical
      cancer. RESULTS: Cervical cancer screening performed between 3 and 36 months
      before the index date was protective against invasive cervical cancer in women
      aged 40 through 69 years. In women younger than 40 years, cervical cancer
      screening performed 3 to 36 months before the index date was not protective.
      CONCLUSIONS: Cervical screening is associated with a reduced risk for invasive
      cervical cancer among women older than 40 years. Cervical cancer resources should
      be focused on maximizing the risk reduction.

PMID- 25377722
TI  - Obesity-associated gene FTO rs9939609 polymorphism in relation to the risk of
      tuberculosis.
AB  - BACKGROUND: Obesity is known to affect cell-mediated immune responses. Recent
      studies have revealed that genetic polymorphisms in the fat mass and obesity
      associated (FTO) gene are related to human obesity. We hypothesize that this gene
      may also play a role in the risk of immune-related infectious diseases such as
      tuberculosis. METHODS: This case-control study included 1625 pulmonary
      tuberculosis cases and 1570 unaffected controls recruited from the Jiangsu
      province in China. Single nucleotide polymorphisms (SNPs), rs9939609 and
      rs8050136, in the FTO gene were genotyped using TaqMan allelic discrimination
      assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
      using the unconditional logistic regression model. RESULTS: We observed a
      significant association between the genetic polymorphism rs9939609 and
      tuberculosis risk. Compared with the common genotype TT, individuals carrying AA
      had a significantly increased risk, with an OR of 3.77 (95% CI: 2.26-6.28). After
      adjusting for potential confounders, the relationship remains significant. An
      additive model showed that carriers of an allele A had a 26% increased risk of
      tuberculosis compared with the T allele (OR: 1.26, 95% CI: 1.08-1.48). Compared
      with the common haplotype rs9939609T-rs8050136C, the haplotype rs9939609A
      rs8050136C was related to an increased risk of tuberculosis (OR = 6.09, 95% CI:
      3.27-12.34). CONCLUSIONS: The FTO polymorphism rs9939609 is associated with a
      risk of pulmonary tuberculosis in the Chinese population.

PMID- 25377726
TI  - Secretoneurin gene therapy improves hind limb and cardiac ischaemia in Apo E-/-
      mice without influencing systemic atherosclerosis.
AB  - AIMS: Hypercholesterolaemia is a major risk factor for cardiovascular diseases
      and has been shown to influence angiogenesis in the hind limb ischaemia (HLI)
      model. The impaired up-regulation of angiogenic factors seems to be one of the
      underlying mechanisms for reduced vessel formation. Since we found that
      secretoneurin (SN) is up-regulated in hypoxic skeletal muscle cells and exerts
      beneficial effects in myocardial and HLI, we hypothesized that SN therapy might
      improve neovascularization in hypercholesterolaemic Apo E(-/-) (Apo E knockout)
      mice suffering from an impaired vascular response. METHODS AND RESULTS: For in
      vitro experiments, endothelial cells (ECs) were incubated with oxidized low
      density lipoprotein (oxLDL) to mimic hypercholesterolaemia. EC function was
      impaired by oxLDL, but SN induced EC proliferation and in vitro tube formation
      under these conditions. In the HLI model, injection of SN plasmid resulted in a
      significant better outcome regarding blood flow recovery, amputation rate, and
      vessel density. In the myocardial infarction (MI) model, the SN group showed
      improvement in cardiac parameters. Aortic plaque area was not influenced by local
      SN injection. Interestingly, SN-induced recruitment of angiogenic monocytic cells
      was abolished under hypercholesterolaemia. CONCLUSIONS: SN gene therapy exerts
      beneficial effects in cardiovascular animal models in Apo E(-/-) mice without
      influencing atherosclerosis and might qualify as a promising therapy for
      cardiovascular disorders.

PMID- 25377727
TI  - Syringin may exert sleep-potentiating effects through the NOS/NO pathway.
AB  - Sleep is essential for basic survival as well as for optimal physical and
      cognitive performance in both human beings and animals. To investigate the effect
      of syringin on sleep of anesthetized mice and the potential mechanisms, 35 male
      Kunming mice were randomly divided into six experimental groups (n = 5) and one
      control group (n = 5). Sleep latency and sleep duration, as well as nitric oxide
      (NO) content and nitric oxide synthase (NOS) activity, were determined after
      syringin administration. The NO precursor l-Arginine (l-Arg) or NOS inhibitor NG
      Nitro-l-arginine methyl ester (l-NAME) was administered alone or in combination
      with syringin, and time for sleep latency and duration was recorded. After
      intragastric administration of syringin, sleep latency decreased in a dose- and
      time-dependent manner, concomitant with increased sleep duration. The optimal
      sleep performance was obtained when syringin was given at a dose of 80 mg/kg for
      eight consecutive days. Syringin significantly reduced NO concentration and NOS
      activity. Administration of l-Arg prolonged sleep latency and shortened sleep
      duration, and the effects were fully reversed by syringin coadministration.
      Administration of L-NAME induced a significant reduction in sleep latency and a
      corresponding increase in sleep duration, and coadministration of syringin
      further enhanced the effects. The finding of our study demonstrated that syringin
      could exert sleep-potentiating effects on anesthetized mice in a time- and dose
      dependent manner, and these effects may be intimately correlated with the NO/NOS
      pathway. 

PMID- 25377728
TI  - Mastoid obliteration for pediatric suppurative cholesteatoma: long-term safety
      and sustained effectiveness after 30 years' experience with cartilage
      obliteration.
AB  - OBJECTIVE: To analyze the long-term safety of mastoid obliteration with cartilage
      in children with suppurative cholesteatomatous ears. METHODS: The medical records
      of children (<=18 years) with cholesteatomas after primary tympanomastoidectomies
      were performed with cartilage obliteration over a 30-year period (1982-2012) were
      analyzed. The recidivism rate was calculated using the Kaplan-Meier survival
      analysis. Potentially confounding factors of recidivism were entered into a Cox
      regression model as covariates for multivariate analysis. RESULTS: Of the 150
      cholesteatomatous ears in 146 children, there were 95 discharging ears (63%) in
      94 children. Among the 95 discharging ears, tympanomastoidectomy was performed
      with cartilage obliteration (CO group) in 77 ears (81%) and without cartilage
      obliteration (WO group) in 18 ears (19%). The mean follow-up period was 12 years.
      Recidivism was observed in 16 ears in the CO group and 4 ears in the WO group.
      The 10-year cumulative recidivism rates were comparable between the CO and WO
      groups (19 vs. 25%, p = 0.762). Multivariate analysis confirmed that mastoid
      obliteration was not a negative predictor of recidivism (p = 0.760). Recidivism
      of cholesteatoma was detected within 6.5 years after surgery in the WO group and
      was found as late as 16.1 years after surgery in the CO group. Cartilage could be
      maintained in the cavity with limited resorption, preventing reretraction pockets
      and subsequent recidivism. CONCLUSION: This study provides evidence supporting
      the long-term safety, feasibility and effectiveness of mastoid cartilage
      obliteration for children with suppurative cholesteatomatous ears. Despite
      comparable recidivism rates between the groups, the potential for the delayed
      detection of recidivism with cavity obliteration may warrant long-term follow-up,
      with careful attention paid to the potential for recidivism during postoperative
      care in children.

PMID- 25377729
TI  - Contrasting effects of sulfur dioxide on cupric oxide and chloride during
      thermochemical formation of chlorinated aromatics.
AB  - Sulfur dioxide (SO2) gas has been reported to be an inhibitor of polychlorinated
      dibenzo-p-dioxins and furans (PCDD/Fs) formation in fly ash. However, other
      research has suggested little or no inhibitory effect of SO2 gas. Although these
      studies focused on reactions between SO2 gas and gas-phase chlorine (Cl) species,
      no attention was paid to thermochemical gas-solid reactions. In this study, we
      found contrasting effects of SO2 gas depending on the chemical form of copper
      (CuO vs CuCl2) with a solid-phase inorganic Cl source (KCl). Chlorinated
      aromatics (PCDD/Fs, polychlorinated biphenyls, and chlorobenzenes) increased and
      decreased in model fly ash containing CuO + KCl and CuCl2 + KCl, respectively,
      with increased SO2 injection. According to in situ Cu K-edge and S K-edge X-ray
      absorption spectroscopy, Cl gas and CuCl2 were generated and then promoted the
      formation of highly chlorinated aromatics after thermochemical reactions of SO2
      gas with the solid-phase CuO + KCl system. In contrast, the decrease in aromatic
      Cls in a CuCl2 + KCl system with SO2 gas was caused mainly by the partial
      sulfation of the Cu. The chemical form of Cu (especially the oxide/chloride
      ratio) may be a critical factor in controlling the formation of chlorinated
      aromatics using SO2 gas. 

PMID- 25377731
TI  - High-gain subnanowatt power consumption hybrid complementary logic inverter with
      WSe2 nanosheet and ZnO nanowire transistors on glass.
AB  - A 1D-2D hybrid complementary logic inverter comprising of ZnO nanowire and WSe2
      nanosheet field-effect transistors (FETs) is fabricated on glass, which shows
      excellent static and dynamic electrical performances with a voltage gain of ~60,
      sub-nanowatt power consumption, and at least 1 kHz inverting speed. 

PMID- 25377730
TI  - Interaction between positive allosteric modulators and trapping blockers of the
      NMDA receptor channel.
AB  - BACKGROUND AND PURPOSE: Memantine and ketamine are clinically used, open-channel
      blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities
      despite strikingly different clinical profiles. Although NMDA channel gating
      constitutes an important difference between memantine and ketamine, it is unclear
      how positive allosteric modulators (PAMs) might affect the pharmacodynamics of
      these NMDA blockers. EXPERIMENTAL APPROACH: We used two different PAMs: SGE-201,
      an analogue of an endogenous oxysterol, 24S-hydroxycholesterol, along with
      pregnenolone sulphate (PS), to test on memantine and ketamine responses in single
      cells (oocytes and cultured neurons) and networks (hippocampal slices), using
      standard electrophysiological techniques. KEY RESULTS: SGE-201 and PS had no
      effect on steady-state block or voltage dependence of a channel blocker. However,
      both PAMs increased the actions of memantine and ketamine on phasic excitatory
      post-synaptic currents, but neither revealed underlying pharmacodynamic
      differences. SGE-201 accelerated the re-equilibration of blockers during voltage
      jumps. SGE-201 also unmasked differences among the blockers in neuronal networks 
      measured either by suppression of activity in multi-electrode arrays or by
      neuroprotection against a mild excitotoxic insult. Either potentiating NMDA
      receptors while maintaining the basal activity level or increasing
      activity/depolarization without potentiating NMDA receptor function is sufficient
      to expose pharmacodynamic blocker differences in suppressing network function and
      in neuroprotection. CONCLUSIONS AND IMPLICATIONS: Positive modulation revealed no
      pharmacodynamic differences between NMDA receptor blockers at a constant voltage,
      but did expose differences during spontaneous network activity. Endogenous
      modulator tone of NMDA receptors in different brain regions may underlie
      differences in the effects of NMDA receptor blockers on behaviour.

PMID- 25377732
TI  - Activity-related parenting practices: development of the Parenting Related to
      Activity Measure (PRAM) and links with mothers' eating psychopathology and
      compulsive exercise beliefs.
AB  - This is a two-study paper that developed a measure to assess parenting practices
      related to children's physical activity and explored maternal predictors of such
      parenting practices. Study 1: A self-report measure of parents' activity-related
      practices (the Parenting Related to Activity Measure) was developed, and a
      principal component analysis was carried out using data from 233 mothers of 4.5-
      to 9-year-old children. The results supported a six-factor model and yielded the
      following subscales: Responsibility/monitoring; Activity regulation; Control of
      active behaviours; Overweight concern; Rewarding parenting; and Pressure to
      exercise. Study 2: Mothers (N = 170) completed the Parenting Related to Activity
      Measure, alongside measures of eating psychopathology and compulsive exercise, to
      identify predictors of activity-related parenting practices. Mothers' eating
      psychopathology and exercise beliefs predicted activity parenting practices with
      their sons and daughters, but different predictors were seen for mothers of
      daughters versus sons. Mothers' eating and exercise attitudes are important
      predictors of their activity-related parenting practices, particularly with
      girls. Identifying early interactions around activity/exercise could be important
      in preventing the development of problematic beliefs about exercise, which are
      often a key symptom of eating disorders. Copyright (c) 2014 John Wiley & Sons,
      Ltd and Eating Disorders Association. 

PMID- 25377733
TI  - The demise of gatekeeping in primary care.

PMID- 25377734
TI  - The evolving role of cardiac computed tomography angiography in an era of limited
      resources.

PMID- 25377735
TI  - The NHS: celebrated and damned.

PMID- 25377736
TI  - Emergency hospital admissions via accident and emergency departments in England:
      time trend, conceptual framework and policy implications.

PMID- 25377737
TI  - The mustard gas experiments done by the British Homoeopathic Society for the
      Ministry of Home Security, 1941-1942.

PMID- 25377741
TI  - Recent advances of proteomics applied to human diseases.

PMID- 25377742
TI  - Serum antibody signature directed against Candida albicans Hsp90 and enolase
      detects invasive candidiasis in non-neutropenic patients.
AB  - Invasive candidiasis (IC) adds significantly to the morbidity and mortality of
      non-neutropenic patients if not diagnosed and treated early. To uncover serologic
      biomarkers that alone or in combination could reliably detect IC in this
      population, IgG antibody-reactivity profiles to the Candida albicans
      intracellular proteome were examined by serological proteome analysis (SERPA) and
      data mining procedures in a training set of 24 non-neutropenic patients. Despite
      the high interindividual molecular heterogeneity, unsupervised clustering
      analyses revealed that serum 22-IgG antibody-reactivity patterns differentiated
      IC from non-IC patients. Univariate analyses further highlighted that 15 out of
      the 22 SERPA-identified IgG antibodies could be useful candidate IC biomarkers.
      The diagnostic performance of one of these candidates (anti-Hsp90 IgG antibodies)
      was validated using an ELISA prototype in a test set of 59 non-neutropenic
      patients. We then formulated an IC discriminator based on the combined
      immunoproteomic fingerprints of this and another SERPA-detected and previously
      validated IC biomarker (anti-Eno1 IgG antibodies) in the training set. Its
      consistency was substantiated using their ELISA prototypes in the test set.
      Receiver-operating-characteristic curve analyses showed that this two-biomarker
      signature accurately identified IC in non-neutropenic patients and provided
      better IC diagnostic accuracy than the individual biomarkers alone. We conclude
      that this serum IgG antibody signature directed against C. albicans Hsp90 and
      Eno1, if confirmed prospectively, may be useful for IC diagnosis in non
      neutropenic patients. 

PMID- 25377743
TI  - Body mass index and health service utilisation in the older population: results
      from The Irish Longitudinal Study on Ageing.
AB  - BACKGROUND: obesity is associated with higher healthcare costs in older people;
      however, estimates are predominantly based on the use of primary and secondary
      services. Our objective was to estimate the effect of overweight and obesity on
      the use and cost of allied health services among middle-aged and older people.
      METHODS: the study used data from The Irish Longitudinal Study of Ageing (TILDA),
      a nationally representative study of adults aged >=50 sampled using multistage
      stratified clustered sampling, which included objective measures of height and
      weight. Body mass index was categorised as normal (18.5-24.99 kg/m(2)),
      overweight (25.00-29.99 kg/m(2)), moderate obesity (30.00-34.99 kg/m(2)), severe
      obesity (35.00-39.99 kg/m(2)) or morbid obesity (>=40 kg/m(2)). Participants were
      asked about a range of allied health services including dietetic services, public
      health nurse visits, chiropody and home help. Adjusted seemingly unrelated
      biprobit models were used to account for unobserved heterogeneity associated with
      the use of services. RESULTS: among 5,841 participants, 77.6% (95% CI = 76-79%)
      were overweight or obese (n = 4,534). All classes of obesity were significantly
      associated with higher general practitioner service use (P < 0.05). Moderate and
      severe obesity were associated with increased use of out-patient services, while
      only moderate obesity was associated with increased hospital admissions (P <
      0.05). Moderate and severe obesity were significantly associated with chiropody
      service use (P < 0.05) with an estimated annual cost of ?919,662. Morbid obesity
      was associated with dietetic service use (P < 0.001) with an annual cost of
      ?580,013. CONCLUSION: given these costs and improvements in life expectancy, an
      increasingly obese older population presents new challenges for healthcare
      delivery.

PMID- 25377744
TI  - Objectively assessed physical activity and lower limb function and prospective
      associations with mortality and newly diagnosed disease in UK older adults: an
      OPAL four-year follow-up study.
AB  - BACKGROUND: Objective measures of physical activity and function with a diverse
      cohort of UK adults in their 70s and 80s were used to investigate relative risk
      of all-cause mortality and diagnoses of new diseases over a 4-year period.
      PARTICIPANTS: Two hundred and forty older adults were randomly recruited from 12
      general practices in urban and suburban areas of a city in the United Kingdom.
      Follow-up included 213 of the baseline sample. METHODS: Socio-demographic
      variables, height and weight, and self-reported diagnosed diseases were recorded
      at baseline. Seven-day accelerometry was used to assess total physical activity,
      moderate-to-vigorous activity and sedentary time. A log recorded trips from home.
      Lower limb function was assessed using the Short Physical Performance Battery.
      Medical records were accessed on average 50 months post baseline, when new
      diseases and deaths were recorded. ANALYSES: ANOVAs were used to assess socio
      demographic, physical activity and lower limb function group differences in
      diseases at baseline and new diseases during follow-up. Regression models were
      constructed to assess the prospective associations between physical activity and
      function with mortality and new disease. RESULTS: For every 1,000 steps walked
      per day, the risk of mortality was 36% lower (hazard ratios 0.64, 95% confidence
      interval (CI) 0.44-0.91, P=0.013). Low levels of moderate-to-vigorous physical
      activity (incident rate ratio (IRR) 1.67, 95% CI 1.04-2.68, P=0.030) and low
      frequency of trips from home (IRR 1.41, 95% CI 0.98-2.05, P=0.045) were
      associated with diagnoses of more new diseases. CONCLUSION: Physical activity
      should be supported for adults in their 70s and 80s, as it is associated with
      reduced risk of mortality and new disease development.

PMID- 25377746
TI  - The second national audit of intermediate care.
AB  - Intermediate care services have developed internationally to expedite discharge
      from hospital and to provide an alternative to an emergency hospital admission.
      Inconsistencies in the evidence base and under-developed governance structures
      led to concerns about the care quality, outcomes and provision of intermediate
      care in the NHS. The National Audit of Intermediate Care was therefore
      established by an interdisciplinary group. The second national audit reported in
      2013 and included crisis response teams, home-based and bed-based services in
      approximately a half of the NHS. The main findings were evidence of weak local
      strategic planning, considerable under-provision, delays in accessing the
      services and lack of mental health involvement in care. There was a very high
      level of positive patient experience reported across all types of intermediate
      care, though reported involvement with care decisions was less satisfactory. 

PMID- 25377745
TI  - Cognitive motor interference for preventing falls in older adults: a systematic
      review and meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: We conducted a systematic review to determine the effect of cognitive
      motor interference (CMI) for the prevention of falls in older adults. METHODS: We
      searched studies through Medline, Embase, the Cochrane Library, Web of Science,
      CINAHL, PEDro and the China Biology Medicine disc. Only randomised controlled
      trials examining the effects of CMI for older people were included. The primary
      outcome measure was falls; the secondary outcome measures included gait, balance
      function and reaction time. RESULTS: A total of 30 studies of 1,206 participants
      met the inclusion criteria, and 27 studies of 1,165 participants were used as
      data sources for the meta-analyses. The pooling revealed that CMI was superior to
      control group for fall rate [standard mean difference (SMD) (95% CI)=-3.03 (
      4.33, -1.73), P<0.0001], gait speed [SMD (95% CI)=0.36 (0.07, 0.66), P=0.01],
      step length [SMD (95% CI)=0.48 (0.16, 0.80), P=0.003], cadence [SMD (95% CI)=0.19
      (0.01, 0.36), P=0.03], timed up and go test [SMD (95% CI)=-0.22 (-0.38, -0.06),
      P=0.007], centre of pressure displacement [SMD (95% CI)=-0.32 (-1.06, 0.43),
      P=0.04] and reaction time [SMD (95% CI)=-0.47 (-0.86, -0.08), P=0.02].
      CONCLUSION: The systematic review demonstrates that CMI is effective for
      preventing falls in older adults in the short term. However, there is, as yet,
      little evidence to support claims regarding long-term benefits. Hence, future
      studies should investigate the long-term effectiveness of CMI in terms of fall
      prevention in older adults.

PMID- 25377747
TI  - A systems approach towards an intelligent and self-controlling platform for
      integrated continuous reaction sequences.
AB  - Performing reactions in flow can offer major advantages over batch methods.
      However, laboratory flow chemistry processes are currently often limited to
      single steps or short sequences due to the complexity involved with operating a
      multi-step process. Using new modular components for downstream processing,
      coupled with control technologies, more advanced multi-step flow sequences can be
      realized. These tools are applied to the synthesis of 2-aminoadamantane-2
      carboxylic acid. A system comprising three chemistry steps and three workup steps
      was developed, having sufficient autonomy and self-regulation to be managed by a
      single operator. 

PMID- 25377748
TI  - Increasing trends in the incidence and prevalence rates of type 1 diabetes among
      children and adolescents in the Netherlands.
AB  - OBJECTIVE: To assess the trends in the incidence and prevalence rates of type 1
      diabetes (T1D) among children and adolescents in the Netherlands. METHODS: A
      population-based cohort study was conducted in the Dutch PHARMO record linkage
      system (1998-2011). All children and adolescents aged <=19 yr with at least one
      insulin dispensing (as a proxy for T1D) were identified and the numbers of
      incident and prevalent cases (numerators) were calculated. Overall age-adjusted
      (0-19 yr) incidence and prevalence rates together with age- and sex-specific
      rates of T1D and their 95% confidence intervals (CI) were calculated using data
      from the Dutch Central Bureau of Statistics as denominator. Trends over time were
      assessed using Joinpoint regression software (National Cancer Institute,
      Bethesda, MD, USA). RESULTS: In 2011, the overall age-adjusted incidence and
      prevalence rates of T1D were 25.2/100 000 (95% CI, 23.7-26.8) person-years (PY)
      and 174.4/100 000 (95% CI, 170.2-178.5) children, respectively. The average
      annual percentage change (AAPC) in the overall age-adjusted incidence and
      prevalence rate was 3.7% (95% CI, 1.8-5.7) and 3.8% (95% CI, 2.4-5.2),
      respectively. While during the study period the largest increases in the
      incidence and prevalence rates of T1D were observed for the oldest age groups (10
      14 and 15-19 yr), a decreasing trend was detected for the 0- to 4-yr-old category
      (with AAPCs of -1.8 (95% CI, -9.9 to 7.1) and -6.9% (95% CI, -11.5 to -2.1) for
      incidence and prevalence, respectively). CONCLUSION: Age-adjusted incidence (1999
      2011) and prevalence rates (1998-2011) of T1D in Dutch children (aged 0-19 yr)
      continued to increase and a shift was observed to a later onset of the disease.

PMID- 25377749
TI  - Geographical distribution of indoor radon and related geological characteristics
      in Bonghwa County, a provisional radon-prone area in Korea.
AB  - The detailed indoor radon survey was conducted during a year (from September 2012
      to August 2013) quarterly in Bonghwa county, one of the provisional radon-prone
      areas in Korea. The surveyed area was selected on the basis of previously
      conducted nationwide radon survey results. In order to minimise statistical and
      environmental uncertainties, ~3 % of the entire dwellings were carefully selected
      based on the statistical annual report of Bonghwa county. The measurement is
      carried out by using solid-state nuclear track detector. The range of indoor
      radon concentration in each dwelling was 4.36-858 Bq m(-3) and that of annual
      effective dose due to inhaled radon of the resident in each dwelling was 0.19
      23.5 mSv y(-1). Each dwelling was determined for geology criterion using one-way
      Analysis of Variance for the purpose of comparing indoor radon distribution with
      geology. Geographical distribution of indoor radon is closely related to the
      geological characteristics of basement rocks. In addition, the comparison between
      geographical distribution of indoor radon and terrestrial gamma radiation was
      done.

PMID- 25377750
TI  - Radiation exposure during paediatric CT in Sudan: CT dose, organ and effective
      doses.
AB  - The purpose of this study was to assess the magnitude of radiation exposure
      during paediatric CT in Sudanese hospitals. Doses were determined from CT
      acquisition parameters using CT-Expo 2.1 dosimetry software. Doses were evaluated
      for three patient ages (0-1, 1-5 and 5-10 y) and two common procedures (head and
      abdomen). For children aged 0-1 y, volume CT air kerma index (Cvol), air Kerma
      length product and effective dose (E) values were 19.1 mGy, 265 mGy.cm and 3.1
      mSv, respectively, at head CT and those at abdominal CT were 8.8 mGy, 242 mGy.cm
      and 7.7 mSv, respectively. Those for children aged 1-5 y were 22.5 mGy, 305
      mGy.cm and 1.1 mSv, respectively, at head CT and 12.6 mGy, 317 mGy.cm, and 5.1
      mSv, respectively, at abdominal CT. Dose values and variations were comparable
      with those reported in the literature. Organ equivalent doses vary from 7.5 to
      11.6 mSv for testes, from 9.0 to 10.0 mSv for ovaries and from 11.1 to 14.3 mSv
      for uterus in abdominal CT. The results are useful for dose optimisation and
      derivation of national diagnostic reference levels.

PMID- 25377751
TI  - Comparison of two methods for high purity germanium detector efficiency
      calibration for charcoal canister radon measurement.
AB  - The charcoal canister method of radon measurement according to US Environment
      Protection Agency protocol 520/5-87-005 is widely used for screening. This method
      is based on radon adsorption on coal and measurement of gamma radiation of radon
      daughters. For the purpose of gamma spectrometry, appropriate efficiency
      calibration of the measuring system must be performed. The most usual method of
      calibration is using standard canister, a sealed canister with the same matrix
      and geometry as the canisters used for measurements, but with the known activity
      of radon. In the absence of standard canister, a different method of efficiency
      calibration has to be implemented. This study presents the results of efficiency
      calibration using the EFFTRAN efficiency transfer software. Efficiency was
      calculated using a soil matrix cylindrical secondary reference material as a
      starting point. Calculated efficiency is then compared with the one obtained
      using standard canister and applied to a realistic measurement in order to
      evaluate the results of the efficiency transfer. 

PMID- 25377752
TI  - Radioactive source security: the cultural challenges.
AB  - Radioactive source security is an essential part of radiation protection. Sources
      can be abandoned, lost or stolen. If they are stolen, they could be used to cause
      deliberate harm and the risks are varied and significant. There is a need for a
      global security protection system and enhanced capability to achieve this. The
      establishment of radioactive source security requires 'cultural exchanges'. These
      exchanges include collaboration between: radiation protection specialists and
      security specialists; the nuclear industry and users of radioactive sources;
      training providers and regulators/users. This collaboration will facilitate
      knowledge and experience exchange for the various stakeholder groups, beyond
      those already provided. This will promote best practice in both physical and
      information security and heighten security awareness generally. Only if all
      groups involved are prepared to open their minds to listen to and learn from,
      each other will a suitable global level of control be achieved. 

PMID- 25377753
TI  - Radiation protection challenges in the management of radioactive waste from high
      energy accelerators.
AB  - The European Laboratory for Particle Physics (CERN) has operated high-energy
      accelerators for fundamental physics research for nearly 60 y. The side-product
      of this activity is the radioactive waste, which is mainly generated as a result
      of preventive and corrective maintenance, upgrading activities and the
      dismantling of experiments or accelerator facilities. Prior to treatment and
      disposal, it is common practice to temporarily store radioactive waste on CERN's
      premises and it is a legal requirement that these storage facilities are safe and
      secure. Waste treatment typically includes sorting, segregation, volume and size
      reduction and packaging, which will depend on the type of component, its chemical
      composition, residual activity and possible surface contamination. At CERN, these
      activities are performed in a dedicated waste treatment centre under the
      supervision of the Radiation Protection Group. This paper gives an overview of
      the radiation protection challenges in the conception of a temporary storage and
      treatment centre for radioactive waste in an accelerator facility, based on the
      experience gained at CERN. The CERN approach consists of the classification of
      waste items into 'families' with similar radiological and physical-chemical
      properties. This classification allows the use of specific, family-dependent
      techniques for radiological characterisation and treatment, which are
      simultaneously efficient and compliant with best practices in radiation
      protection. The storage was planned on the basis of radiological and other
      possible hazards such as toxicity, pollution and fire load. Examples are given of
      technical choices for the treatment and radiological characterisation of selected
      waste families, which could be of interest to other accelerator facilities. 

PMID- 25377754
TI  - Apparent mortality as a result of an elevated parasite infection in Presbytis
      rubicunda.
AB  - We provide the first parasite assessment of wild red langurs (Presbytis
      rubicunda). Seven helminth taxa and 4 protozoa were recovered from faecal
      samples. We report the details of the death of an adult female red langur with
      potential association of an elevated parasite infection. There is a paucity of
      published literature on red langurs and nothing is known of the factors affecting
      interspecific parasite transmission and disease spread between other primate
      species. Parasites may be substantial determinants of host health and may present
      a significant influence on the survival and reproduction of individuals and the
      subsequent fecundity of populations. Further research into the connection of
      parasite burden with individual deaths and potential population declines is
      recommended for monitoring population health.

PMID- 25377755
TI  - Medicinal marijuana for epilepsy: a case series study.
AB  - OBJECTIVE: To describe the social, clinical and use-patterns characteristics of
      medicinal marijuana use among patients with epilepsy (PWEs). METHODS: Eighteen
      PWEs with prescriptions for medicinal marijuana from a Canadian adult-epilepsy
      clinic were included in this study. RESULTS: Eighteen patients had a prescription
      of medicinal marijuana from a total population of 800 PWEs in our center (2.2%).
      Mean age of patients was 30+/-7.4 (19-50) years. Twelve (67%) patients were
      males. Eleven (61%) patients had drug-resistant epilepsy. Eleven (61%) patients
      suffered a psychiatric comorbidity and reported the use of illicit substances or
      heavy alcohol or tobacco consumption. Only two (11%) patients were married; the
      rest of patients (89%) were single or divorced. The drug use pattern was similar
      among patients. All patients asked for marijuana permission in the epilepsy
      clinic. Most (83%) had a previous history of marijuana smoking, with a mean of
      6.6+/-3 (1-15) years. The mean consumption dose was 2.05+/-1.8 (0.5-8) grams per
      day. Ten (56%) patients reported withdrawal seizure exacerbation when they
      stopped the marijuana. Only two patients (11%) reported side effects, and all
      patients found medicinal marijuana very helpful for seizure control and
      improvement of mood disorder. CONCLUSIONS: PWEs using medicinal marijuana have a
      common profile. They are usually young single men with drug-resistant epilepsy
      and psychiatric comorbidity. Most used marijuana before formal prescription and
      all believe the drug was effective on their seizure control. Because of the
      concurrent use of other antiseizure medications, it is complex to estimate the
      actual effect of marijuana.

PMID- 25377756
TI  - Feasibility of extreme dose escalation for glioblastoma multiforme using 4pi
      radiotherapy.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) frequently recurs at the same location
      after radiotherapy. Further dose escalation using conventional methods is limited
      by normal tissue tolerance. 4pi non-coplanar radiotherapy has recently emerged as
      a new potential method to deliver highly conformal radiation dose using the C-arm
      linacs. We aim to study the feasibility of very substantial GBM dose escalation
      while maintaining normal tissue tolerance using 4pi. METHODS: 11 GBM patients
      previously treated with volumetric modulated arc therapy (VMAT/RapidArc) on the
      NovalisTxTM platform to a prescription dose of either 59.4 Gy or 60 Gy were
      included. All patients were replanned with 30 non-coplanar beams using a 4pi
      radiotherapy platform, which inverse optimizes both beam angles and fluence maps.
      Four different prescriptions were used including original prescription dose and
      PTV (4piPTVPD), 100 Gy to the PTV and GTV (4piPTV100Gy), 100 Gy to the GTV only
      while maintaining prescription dose to the rest of the PTV (4piGTV100Gy), and a 5
      mm margin expansion plan (4piPTVPD+5mm). OARs included in the study are the
      normal brain (brain - PTV), brainstem, chiasm, spinal cord, eyes, lenses, optical
      nerves, and cochleae. RESULTS: The 4pi plans resulted in superior dose gradient
      indices, as indicated by >20% reduction in the R50, compared to the clinical
      plans. Among all of the 4pi cases, when compared to the clinical plans, the
      maximum and mean doses were significantly reduced (p < 0.05) by a range of 47.01
      98.82% and 51.87-99.47%, respectively, or unchanged (p > 0.05) for all of the non
      brain OARs. Both the 4piPTVPD and 4pi GTV100GYplans reduced the mean normal brain
      mean doses. CONCLUSIONS: 4pi non-coplanar radiotherapy substantially increases
      the dose gradient outside of the PTV and better spares critical organs. Dose
      escalation to 100 Gy to the GTV or additional margin expansion while meeting
      clinical critical organ dose constraints is feasible. 100 Gy to the PTV result in
      higher normal brain doses but may be tolerated when delivered in proportionally
      increased treatment fractions. Therefore, 4pi non-coplanar radiotherapy on C-arm
      gantry may provide an accessible tool to improve the outcome of GBM radiotherapy
      through extreme dose escalation.

PMID- 25377757
TI  - Genitofemoral neuralgia: a review.
AB  - Genitofemoral neuralgia is a cause of neuropathic pain that is often debilitating
      in nature. It is characterized by chronic neuropathic groin pain that is
      localized along the distribution of the genitofemoral nerve. The symptoms include
      groin pain, paresthesias, and burning sensation spreading from the lower abdomen
      to the medial aspect of the thigh. It may present with scrotal pain in male,
      while females experience symptoms radiating to the labia majora and mons pubis.
      Genitofemoral neuropathy has been attributed to iatrogenic nerve injury occurring
      during inguinal and femoral herniorrhaphy, with cases developing after both open
      and laparoscopic techniques. Diagnosis of genitofemoral neuralgia can be
      challenging, due to the overlap in sensory distribution the nerve shares with the
      ilioinguinal and iliohypogastric nerve. Differential nerve blocks are recommended
      in effort to differentiate the nerves when patients present with lower abdominal
      and groin pain. Once a diagnosis has been made, there exist several treatment
      options for genitofemoral neuralgia ranging from medical management, non-invasive
      injections, and surgery. Literature has also brought light to radiofrequency
      ablation and cryoablation performed under ultrasound guidance as emerging
      treatments. The aim of the current article is to review the anatomy, diagnostic
      techniques, and treatment options for patients with genitofemoral neuralgia.

PMID- 25377758
TI  - Description of Events Where African Buffaloes (Syncerus caffer) Strayed from the
      Endemic Foot-and-Mouth Disease Zone in South Africa, 1998-2008.
AB  - African buffaloes (Syncerus caffer) are reservoir hosts of Southern African
      Territories (SAT) foot-and-mouth disease (FMD) virus strains. In South Africa,
      infected buffaloes are found in the FMD-infected zone comprising the Kruger
      National Park (KNP) and its adjoining reserves. When these buffaloes stray into
      livestock areas, they pose a risk of FMD transmission to livestock. We assessed
      645 records of stray buffalo events (3124 animals) from the FMD infected zone
      during 1998-2008 for (i) their temporal distribution, (ii) group size, (iii) age
      and gender composition, (iv) distance from the infected zone fence and (v)
      outcome reported for each event. A maximum entropy model was developed to
      evaluate spatial predictors of stray buffalo events and assess current disease
      control zones. Out of all buffaloes recorded straying, 38.5% escaped from the FMD
      infected zone during 2000/2001, following floods that caused extensive damage to
      wildlife fences. Escape patterns were not apparently influenced by season. The
      median size of stray groups was a single animal (IQR [1-2]). Adult animals
      predominated, comprising 90.4% (620/686) of the animals for which age was
      recorded. Of the 315 events with accurate spatial information, 204 (64.8%) were
      recorded within 1 km from the FMD infected zone. During late winter/spring (June
      October), stray buffaloes were found significantly closer to the FMD infected
      zone (median = 0.3 km, IQR [0.1-0.6]). Less than 13% (40/315) of stray groups
      reached the FMD protection zone without vaccination, posing a higher risk of
      spreading FMD to these more susceptible livestock. Model outputs suggest that
      distance from the FMD infected zone, urban areas and permanent water sources
      contributed almost 85% to the spatial probability of stray buffalo events. Areas
      with a high probability for stray buffalo events were well covered by current
      disease control zones, although FMD risk mitigation could be improved by
      expanding the vaccination zone in certain areas.

PMID- 25377759
TI  - Cooperative dual palladium/silver catalyst for direct difluoromethylation of aryl
      bromides and iodides.
AB  - Difluoromethylated arenes are one of the privileged structural motifs that are
      important for fine tuning the biological properties of drug molecules. No general
      catalytic method exists for the formation of difluoromethylarenes. Previous
      methods for the preparation of difluoromethylarenes typically required harsh
      conditions, multiple steps or stoichiometric amount of catalysts. Here we report
      a cooperative dual palladium/silver catalyst system for direct
      difluoromethylation of aryl bromides and iodides under mild conditions. We
      develop the system by initial preparation of the putative intermediates in the
      dual-catalytic cycles, followed by studying the elemental steps to demonstrate
      the viability of the proposed cooperative catalytic cycle. The reaction is
      compatible with a variety of functional groups such as ester, amide, protected
      phenoxide, protected ketone, cyclopropyl, bromide and heteroaryl subunits such as
      pyrrole, benzothiazole, carbazole or pyridine. 

PMID- 25377760
TI  - Seizure expression, behavior, and brain morphology differences in colonies of
      Genetic Absence Epilepsy Rats from Strasbourg.
AB  - OBJECTIVE: Originally derived from a Wistar rat strain, a proportion of which
      displayed spontaneous absence-type seizures, Genetic Absence Epilepsy Rats from
      Strasbourg (GAERS) represent the most widely utilized animal model of genetic
      generalized epilepsy. Here we compare the seizure, behavioral, and brain
      morphometric characteristics of four main GAERS colonies that are being actively
      studied internationally: two from Melbourne (MELB and STRAS-MELB), one from
      Grenoble (GREN), and one from Istanbul (ISTAN). METHODS: Electroencephalography
      (EEG) recordings, behavioral examinations, and structural magnetic resonance
      imaging (MRI) studies were conducted on GAERS and Non-Epileptic Control (NEC)
      rats to assess and compare the following: (1) characteristics of spike-and-wave
      discharges, (2) anxiety-like and depressive-like behaviors, and (3) MRI brain
      morphology of regions of interest. RESULTS: Seizure characteristics varied
      between the colonies, with MELB GAERS exhibiting the least severe epilepsy
      phenotype with respect to seizure frequency, and GREN GAERS exhibiting four times
      more seizures than MELB. MELB and STRAS-MELB colonies both displayed consistent
      anxiety and depressive-like behaviors relative to NEC. MELB and GREN GAERS showed
      similar changes in brain morphology, including increased whole brain volume and
      increased somatosensory cortical width. A previously identified mutation in the
      Cacna1h gene controlling the CaV 3.2 T-type calcium channel (R1584P) was present
      in all four GAERS colonies, but absent in all NEC rats. SIGNIFICANCE: This study
      demonstrates differences in epilepsy severity between GAERS colonies that were
      derived from the same original colony in Strasbourg. This multi-institute study
      highlights the potential impact of environmental conditions and/or genetic drift
      on the severity of epileptic and behavioral phenotypes in rodent models of
      epilepsy.

PMID- 25377761
TI  - From bench to bed: bridging from informatics theory to practice. An exploratory
      analysis.
AB  - BACKGROUND: In 2009, the journal Applied Clinical Informatics (ACI) commenced
      publication. Focused on applications in clinical informatics, ACI was intended to
      be a companion journal to METHODS of Information in Medicine (MIM). Both journals
      are official journals of IMIA, the International Medical Informatics Association.
      OBJECTIVES: To explore, after five years, which congruencies and
      interdependencies exist in publications of these journals and to determine if
      gaps exist. To achieve this goal, major topics discussed in ACI and in MIM had to
      be analysed. Finally, we wanted to explore, whether the intention of publishing
      these companion journals to provide an information bridge from informatics theory
      to informatics practice and from practice to theory could be supported by this
      model. In this manuscript we will report on congruencies and interdependencies
      from practise to theory and on major topis in ACI. Further results will be
      reported in a second paper. METHODS: Retrospective, prolective observational
      study on recent publications of ACI and MIM. All publications of the years 2012
      and 2013 from these journals were indexed and analysed. RESULTS: Hundred and
      ninety-six publications have been analysed (87 ACI, 109 MIM). In ACI publications
      addressed care coordination, shared decision support, and provider communication
      in its importance for complex patient care and safety and quality. Other major
      themes included improving clinical documentation quality and efficiency,
      effectiveness of clinical decision support and alerts, implementation of health
      information technology systems including discussion of failures and succeses. An
      emerging topic in the years analyzed was a focus on health information technology
      to predict and prevent hospital admissions and managing population health
      including the application of mobile health technology. Congruencies between
      journals could be found in themes, but with different focus in its contents.
      Interdependencies from practise to theory found in these publications, were only
      limited. CONCLUSIONS: Bridging from informatics theory to practise and vice versa
      remains a major component of successful research and practise as well as a major
      challenge.

PMID- 25377762
TI  - Maternal thoughts of harm in response to infant crying: an experimental analysis.
AB  - Ninety-eight mothers of healthy firstborn infants 0 to 6 months old were randomly
      assigned to listen to 10-min of infant crying or infant cooing while continuously
      rating subjective feelings of frustration. Participants completed pre-test
      measures of depressed mood, empathy, and trait anger and post-test measures of
      infant-related harm thoughts, negative and positive emotions, and urge to comfort
      and to flee. Twenty-three (23.5 %) participants endorsed unwanted thoughts of
      active harm (e.g., throwing, yelling at, shaking the infant). Women in the cry
      condition were more likely than women in the coo condition to report thoughts of
      harm. Women in the cry condition who endorsed thoughts of harm reported higher
      frustration levels over the 10 min of crying, higher levels of post-test negative
      emotions, and stronger urges to flee the infant but not stronger urges to comfort
      the infant. Trait anger and personal distress empathy predicted the occurrence of
      unwanted thoughts of infant harm, whereas negative mood did not. Unwanted,
      intrusive, infant-related thoughts of harm may be triggered by prolonged infant
      crying, are predicted by personal distress empathy and a tendency to experience
      anger, and are associated with higher frustration, negative emotions, and the
      urge to escape the infant. 

PMID- 25377763
TI  - Role for mammalian chitinase 3-like protein 1 in traumatic brain injury.
AB  - Traumatic brain injury (TBI) is accompanied by inflammatory infiltrates and CNS
      tissue response. The astrocytosis associated with TBI has been proposed to have
      both beneficial and detrimental effects on surviving neural tissue. We recently
      observed prominent astrocytic expression of YKL-40/chitinase 3-like protein 1
      (CHI3L1) associated with severity of brain injury. The physiological role of
      CHI3L1 in the CNS is unknown; however, its distribution at the perimeter of
      contusions and temporal course of expression suggested that in TBI it might be an
      important component of the astrocytic response to modulate CNS inflammation. To
      address this hypothesis, we used serially sectioned brains to quantitatively
      compare the neuropathological outcomes of TBI produced by controlled cortical
      impact in wild type (WT) and chi3l1 knockout (KO) mice where the murine YKL-40
      homologue, breast regression protein 39 (BRP-39/CHI3l1), had been homozygously
      disrupted. At 21 days post-injury, chi3l1 KO mice displayed greater astrocytosis
      (increased GFAP staining) in the hemispheres ipsilateral and contralateral to
      impact compared with WT mice. Similarly, Iba1 expression as a measure of
      microglial/macrophage response was significantly increased in chi3l1 KO compared
      with WT in the hemisphere contralateral to impact. We conclude that astrocytic
      expression of CHI3L1 limits the extent of both astrocytic and
      microglial/macrophage facets of neuroinflammation and suggests a novel potential
      therapeutic target for modulating neuroinflammation.

PMID- 25377765
TI  - Letter to the editor: in response to "Consistency among musculoskeletal models:
      caveat utilitor".

PMID- 25377766
TI  - Detecting slipping-like perturbations by using adaptive oscillators.
AB  - This study introduces a novel algorithm to detect unexpected slipping-like
      perturbations based on the comparison between actual leg joint angles and those
      predicted by a pool of adaptive oscillators. The approach grounds on the
      hypothesis that during postural transitions, the difference between these
      datasets diverges and can early signal that the dynamic balance is challenged. To
      test this hypothesis, leg joint angles of twelve healthy young participants were
      recorded while undergoing four different perturbations delivered during steady
      locomotion. Joint angles were estimated after spanning the whole domain of the
      adaptive oscillator dynamics. Results confirmed that the implemented strategy
      allows to early detect a postural transition induced by a slipping-like
      perturbation: the best performance is represented by a mean detection time
      ranging between 150 and 250 ms and a low rate (lower than 10%) of false alarms.
      On the whole, the proposed approach is efficient even if it is based on a quite
      simple threshold-based algorithm. Moreover, it does not need any falling-based
      training before being implemented, is not computationally heavy, and is not
      subject dependent. Finally, since it is based on leg joint angles, it appears
      well suited to be implemented in lower-limb orthoses/prostheses already equipped
      with joint position sensors. 

PMID- 25377764
TI  - Laccase production and metabolic diversity among Flammulina velutipes strains.
AB  - Twelve Flammulina velutipes strains originating from Poland were identified using
      internal transcribed spacer (ITS) region sequencing. Based on the sequences
      obtained, the genomic relationship of the analyzed strains was determined. All F.
      velutipes strains were also characterized using Biolog FF MicroPlates to obtain
      data on C-substrate utilization and mitochondrial activity. The ability to
      decompose various substrates differed among the F. velutipes strains up to five
      times. The highest catabolic activities were characteristic for only two strains
      with capabilities to decompose up to 22 carbon sources. The correlation between
      carbon repression and laccase production by F. velutipes was analyzed based on
      glucose assimilation by these strains. Moreover, the influence of metal ions
      (Cu(2+), Cd(2+)), veratric and ferulic acids, and temperature on laccase
      activities in the analyzed strains was determined. The results obtained proved
      that all the inducers influenced laccase expression in almost all the analyzed
      strains. However, the degree of induction depended not only on the strain used
      but also on the day of the induction. 

PMID- 25377767
TI  - Alterations in sagittal plane knee kinetics in knee osteoarthritis using a
      biomechanical therapy device.
AB  - Knee frontal (adduction/abduction) and sagittal (flexion/extension) moments have
      been implicated in the pathomechanics of knee osteoarthritis (OA). The aim of
      this study was to evaluate the change in the knee sagittal moment in a cohort of
      patients with knee OA undergoing a biomechanical training program. Twenty-five
      female patients with symptomatic medial compartment knee OA were enrolled in a
      customized biomechanical intervention program. All patients underwent consecutive
      gait analyses prior to treatment initiation, and after 3 months and 9 months of
      therapy. Self-evaluative questionnaires, spatiotemporal gait parameters, peak
      knee sagittal moments, knee sagittal impulses, and duration of knee moments were
      compared throughout the duration of therapy. Differences between baseline and
      follow-up values were examined using nonparametric tests. Peak knee flexion
      moment (KFM) at loading response decreased significantly with therapy (p =
      0.001). Duration of KFM and impulse of knee flexion also decreased significantly
      (p = 0.024 and p = 0.029, respectively). These changes were accompanied by
      increased walking velocity, significant pain reduction, and increased functional
      activity. Post-training kinetic evaluation demonstrated profound alterations of
      knee sagittal moments at the loading response KFM. We speculate that knee
      sagittal moments can potentially be improved in patients with knee OA over time
      with a biomechanical training program. 

PMID- 25377769
TI  - Using WatchMinder to Increase the On-Task Behavior of Students with Autism
      Spectrum Disorder.
AB  - This study assessed the use of WatchMinderTM, a vibrating prompt watch, and self
      graphing on the on-task behavior of students with autism spectrum disorder in an
      elementary special education setting. Using a multiple baseline across subjects
      design, results showed an immediate increase in on-task behavior when the
      intervention was introduced. Participants maintained high levels of on-task
      behavior during the follow-up phase. Implications for expanded self-monitoring
      treatment packages are discussed. 

PMID- 25377768
TI  - Pathogenic polyglutamine expansion length correlates with polarity of the
      flanking sequences.
AB  - BACKGROUND: Polyglutamine (polyQ) repeat expansion within coding sequence of a
      soluble protein is responsible for eight autosomal-dominant genetic
      neurodegenerative disorders. These disorders affect cerebellum, striatum, basal
      ganglia and other brain regions. The pathogenic polyQ-expansion threshold in
      these proteins varies from 32Q to 54Q. Understanding the reasons for variability
      in pathogenic polyQ threshold may provide insights into pathogenic mechanisms
      responsible for development of these disorders. FINDINGS: Here we established a
      quantitative correlation between the polarity of the flanking sequences and
      pathogenic polyQ-expansion threshold in this protein family. We introduced an
      "edge polarity index" (EPI) to quantify polarity effects of the flanking regions
      and established a strong correlation between EPI index and critical polyQ
      expansion length in this protein family. Based on this analysis we subdivided
      polyQ-expanded proteins into 2 groups - with strong and weak dependence of polyQ
      threshold on EPI index. The main difference between members of the first and the
      second group is a polarity profile of these proteins outside of polyQ and
      flanking regions. PolyQ proteins are known substrates for proteasome and most
      likely mechanistic explanation for the observed correlation is that proteasome
      may have an impaired ability to process continuous non-polar regions of proteins.
      CONCLUSIONS: The proposed hypothesis provides a quantitative explanation for
      variability in pathogenic threshold among polyQ-expansion disorders, which we
      established to correlate with polarity of flanking regions. To explain these
      results we propose that proteasome is not efficient in processing continuous non
      polar regions of proteins, resulting in release of undigested and partially
      digested fragments. If supported experimentally, our hypothesis may have wide
      implications for further understanding the pathogensis of polyglutamine expansion
      disorders.

PMID- 25377770
TI  - Distinct subsynaptic localization of type 1 metabotropic glutamate receptors at
      glutamatergic and GABAergic synapses in the rodent cerebellar cortex.
AB  - Type 1 metabotropic glutamate (mGlu1) receptors play a pivotal role in different
      forms of synaptic plasticity in the cerebellar cortex, e.g. long-term depression
      at glutamatergic synapses and rebound potentiation at GABAergic synapses. These
      various forms of plasticity might depend on the subsynaptic arrangement of the
      receptor in Purkinje cells that can be regulated by protein-protein interactions.
      This study investigated, by means of the freeze-fracture replica immunogold
      labelling method, the subcellular localization of mGlu1 receptors in the rodent
      cerebellum and whether Homer proteins regulate their subsynaptic distribution. We
      observed a widespread extrasynaptic localization of mGlu1 receptors and confirmed
      their peri-synaptic enrichment at glutamatergic synapses. Conversely, we detected
      mGlu1 receptors within the main body of GABAergic synapses onto Purkinje cell
      dendrites. Although Homer proteins are known to interact with the mGlu1 receptor
      C-terminus, we could not detect Homer3, the most abundant Homer protein in the
      cerebellar cortex, at GABAergic synapses by pre-embedding and post-embedding
      immunoelectron microscopy. We then hypothesized a critical role for Homer
      proteins in the peri-junctional localization of mGlu1 receptors at glutamatergic
      synapses. To disrupt Homer-associated protein complexes, mice were tail-vein
      injected with the membrane-permeable dominant-negative TAT-Homer1a. Freeze
      fracture replica immunogold labelling analysis showed no significant alteration
      in the mGlu1 receptor distribution pattern at parallel fibre-Purkinje cell
      synapses, suggesting that other scaffolding proteins are involved in the peri
      synaptic confinement. The identification of interactors that regulate the
      subsynaptic localization of the mGlu1 receptor at neurochemically distinct
      synapses may offer new insight into its trafficking and intracellular signalling.

PMID- 25377773
TI  - Depression in Parkinson's disease: the effectiveness and risk of pharmacotherapy.
      Clinical review.
AB  - Parkinson's disease (PD) is a neurological disease with a heterogeneous pattern
      of neurological symptoms and concomitant psychiatric syndromes. These syndromes
      are triggered by alterations to neurotransmission that are likely common for both
      neurological and psychiatric symptoms. Syndromes such as depression, anxiety, or
      cognitive impairment can precede motor symptoms of PD and delay its diagnosis.
      Recently, questions related to aetiological factors and treatment strategies of
      depression in PD have become a growing concern of PD researchers. This article
      describes the main features of depression in PD and presents current hypotheses
      on its aetiology and recommended treatment modes.

PMID- 25377772
TI  - Diagnostic performance of CT-arthrography and 1.5T MR-arthrography for the
      assessment of glenohumeral joint cartilage: a comparative study with arthroscopic
      correlation.
AB  - PURPOSE: To compare the diagnostic performance of multi-detector CT arthrography
      (CTA) and 1.5-T MR arthrography (MRA) in detecting hyaline cartilage lesions of
      the shoulder, with arthroscopic correlation. PATIENTS AND METHODS: CTA and MRA
      prospectively obtained in 56 consecutive patients following the same
      arthrographic procedure were independently evaluated for glenohumeral cartilage
      lesions (modified Outerbridge grade >=2 and grade 4) by two musculoskeletal
      radiologists. The cartilage surface was divided in 18 anatomical areas.
      Arthroscopy was taken as the reference standard. Diagnostic performance of CTA
      and MRA was compared using ROC analysis. Interobserver and intraobserver
      agreement was determined by kappa statistics. RESULTS: Sensitivity and
      specificity of CTA varied from 46.4 to 82.4 % and from 89.0 to 95.9 %
      respectively; sensitivity and specificity of MRA varied from 31.9 to 66.2 % and
      from 91.1 to 97.5 % respectively. Diagnostic performance of CTA was statistically
      significantly better than MRA for both readers (all p <= 0.04). Interobserver
      agreement for the evaluation of cartilage lesions was substantial with CTA (kappa
      = 0.63) and moderate with MRA (kappa = 0.54). Intraobserver agreement was almost
      perfect with both CTA (kappa = 0.94-0.95) and MRA (kappa = 0.83-0.87).
      CONCLUSION: The diagnostic performance of CTA and MRA for the detection of
      glenohumeral cartilage lesions is moderate, although statistically significantly
      better with CTA. KEY POINTS: * CTA has moderate diagnostic performance for
      detecting glenohumeral cartilage substance loss. * MRA has moderate diagnostic
      performance for detecting glenohumeral cartilage substance loss. * CTA is more
      accurate than MRA for detecting cartilage substance loss.

PMID- 25377771
TI  - An update on risk factors for cartilage loss in knee osteoarthritis assessed
      using MRI-based semiquantitative grading methods.
AB  - Arthroscopy-based semiquantitative scoring systems such as Outerbridge and Noyes'
      scores were the first to be developed for the purpose of grading cartilage
      defects. As magnetic resonance imaging (MRI) became available for evaluation of
      the osteoarthritic knee joint, these systems were adapted for use with MRI. Later
      on, grading methods such as the Whole Organ Magnetic Resonance Score, the Boston
      Leeds Osteoarthritis Knee Score and the MRI Osteoarthritis Knee Score were
      designed specifically for performing whole-organ assessment of the knee joint
      structures, including cartilage. Cartilage grades on MRI obtained with these
      scoring systems represent optimal outcome measures for longitudinal studies, and
      are designed to enhance understanding of the knee osteoarthritis disease process.
      The purpose of this narrative review is to describe cartilage assessment in knee
      osteoarthritis using currently available MRI-based semiquantitative whole-organ
      scoring systems, and to provide an update on the risk factors for cartilage loss
      in knee osteoarthritis as assessed with these scoring systems.

PMID- 25377774
TI  - Tunable multicolor and white-light upconversion luminescence in Yb3+/Tm3+/Ho3+
      tri-doped NaYF4 micro-crystals.
AB  - NaYF4 micro-crystals with various concentrations of Yb(3+) /Tm(3+) /Ho(3+) were
      prepared successfully via a simple and reproducible hydrothermal route using EDTA
      as the chelating agent. Their phase structure and surface morphology were studied
      using powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The
      XRD patterns revealed that all the samples were pure hexagonal phase NaYF4. SEM
      images showed that Yb(3+)/Tm(3+)/Ho(3+) tri-doped NaYF4 were hexagonal micro
      prisms. Upconversion photoluminescence spectra of Yb(3+)/Tm(3+)/Ho(3+) tri-doped
      NaYF4 micro-crystals with various dopant concentrations under 980 nm excitation
      with a 665 mW pump power were studied. Tunable multicolor (purple, purplish blue,
      yellowish green, green) and white light were achieved by simply adjusting the
      Ho(3+) concentration in 20%Yb(3+)/1%Tm(3+)/xHo(3+) tri-doped NaYF4 micro
      crystals. Furthermore, white-light emissions could be obtained using different
      pump powers in 20%Yb(3+)/1%Tm(3+)/1%Ho(3+) tri-doped NaYF4 micro-crystals at 980
      nm excitation. The pump power-dependent intensity relationship was studied and
      relevant energy transfer processes were discussed in detail. The results suggest
      that Yb(3+)/Tm(3+) Ho(3+) tri-doped NaYF4 micro-crystals have potential
      applications in optoelectronic devices such as photovoltaic, plasma display panel
      and white-light-emitting diodes.

PMID- 25377776
TI  - Expedient construction of the [5-6-7] tricyclic core of calyciphylline a-type
      alkaloids.
AB  - An efficient synthetic route toward the highly congested [5-6-7] tricyclic core
      of calyciphylline A-type alkaloids has been developed. This approach features a
      highly efficient intramolecular Diels-Alder cycloaddition to establish the aza
      five-membered C ring as well as the C1 all-carbon quaternary center, and a
      subsequent cyclopropanation together with a ring-expansion reaction of the
      resulted adduct to construct the seven-membered D ring. 

PMID- 25377775
TI  - Methamphetamine induces a rapid increase of intracellular Ca(++) levels in
      neurons overexpressing GCaMP5.
AB  - In this study, methamphetamine (Meth)- and glutamate (Glu)-mediated intracellular
      Ca(++) (Ca(++) i) signals were examined in real time in primary cortical neurons
      overexpressing an intracellular Ca(++) probe, GCaMP5, by adeno-associated viral
      (AAV) serotype 1. Binding of Ca(++) to GCaMP increased green fluorescence
      intensity in cells. Both Meth and Glu induced a rapid increase in Ca(++) i, which
      was blocked by MK801, suggesting that Meth enhanced Ca(++) i through Glu receptor
      in neurons. The Meth-mediated Ca(++) signal was also blocked by Mg(++) , low
      Ca(++) or the L-type Ca(++) channel inhibitor nifedipine. The ryanodine receptor
      inhibitor dantrolene did not alter the initial Ca(++) influx but partially
      reduced the peak of Ca(++) i. These data suggest that Meth enhanced Ca(++) influx
      through membrane Ca(++) channels, which then triggered the release of Ca(++) from
      the endoplasmic reticulum in the cytosol. AAV-GCaMP5 was also injected to the
      parietal cortex of adult rats. Administration of Meth enhanced fluorescence in
      the ipsilateral cortex. Using immunohistochemistry, Meth-induced green
      fluorescence was found in the NeuN-containing cells in the cortex, suggesting
      that Meth increased Ca(++) in neurons in vivo. In conclusion, we have used in
      vitro and in vivo techniques to demonstrate a rapid increase of Ca(++) i by Meth
      in cortical neurons through overexpression of GCaMP5. As Meth induces behavioral
      responses and neurotoxicity through Ca(++) i, modulation of Ca(++) i may be
      useful to reduce Meth-related reactions. 

PMID- 25377777
TI  - An enhanced droplet-based liquid microjunction surface sampling system coupled
      with HPLC-ESI-MS/MS for spatially resolved analysis.
AB  - Droplet-based liquid microjunction surface sampling coupled with high-performance
      liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass
      spectrometry (MS/MS) for spatially resolved analysis provides the possibility of
      effective analysis of complex matrix samples and can provide a greater degree of
      chemical information from a single spot sample than is typically possible with a
      direct analysis of an extract. Described here is the setup and enhanced
      capabilities of a discrete droplet liquid microjunction surface sampling system
      employing a commercially available CTC PAL autosampler. The system enhancements
      include incorporation of a laser distance sensor enabling unattended analysis of
      samples and sample locations of dramatically disparate height as well as reliably
      dispensing just 0.5 MUL of extraction solvent to make the liquid junction to the
      surface, wherein the extraction spot size was confined to an area about 0.7 mm in
      diameter; software modifications improving the spatial resolution of sampling
      spot selection from 1.0 to 0.1 mm; use of an open bed tray system to accommodate
      samples as large as whole-body rat thin tissue sections; and custom
      sample/solvent holders that shorten sampling time to approximately 1 min per
      sample. The merit of these new features was demonstrated by spatially resolved
      sampling, HPLC separation, and mass spectral detection of pharmaceuticals and
      metabolites from whole-body rat thin tissue sections and razor blade ("crude")
      cut mouse tissue. 

PMID- 25377778
TI  - Characterization and profiling of phenolic amides from Cortex Lycii by ultra-high
      performance liquid chromatography coupled with LTQ-Orbitrap mass spectrometry.
AB  - Cortex Lycii, the root bark of Lycium chinense Mill. or Lycium barbarum L., is a
      frequently used traditional Chinese medicine. Phytochemical studies have shown
      that phenolic amides are not only characteristic compounds but also abundant ones
      in this plant. In the present study, an effective method was developed for
      structural characterization of phenolic amides from Cortex Lycii by ultra-high
      performance liquid chromatography coupled with linear ion trap Orbitrap tandem
      mass spectrometry. The fragmentation of 14 compounds including six cinnamic acid
      amides, six neolignanamides, and two lignanamides were studied systematically for
      the first time. It was found that, in the positive ion mode, neutral loss of the
      tyramide moiety (137 Da) or N-(4-aminobutyl)acetamide moiety (130 Da) were
      characteristic for these compounds. At least 54 phenolic amides were detected in
      the extract and 48 of them were characterized, among which 14 known compounds
      were identified unambiguously by comparing the retention time and mass spectra
      with those of reference compounds, and 34 components were tentatively identified
      based on the fragmentation patterns, exact mass, UV spectra, as well as retention
      time. Fifteen compounds were characterized as potential new ones. Additionally,
      the developed method was applied to analyze eight batches of samples collected
      from the northwest of China, and it was found that cinnamic acid amides were the
      main type of phenolic amides in Cortex Lycii. In conclusion, the identification
      of these chemicals provided essential data for further phytochemical studies,
      metabolites identification, and the quality control of Cortex Lycii. 

PMID- 25377779
TI  - An integrated microfluidic chip enabling control and spatially resolved
      monitoring of temperature in micro flow reactors.
AB  - A strength of microfluidic chip laboratories is the rapid heat transfer that, in
      principle, enables a very homogeneous temperature distribution in chemical
      processes. In order to exploit this potential, we present an integrated chip
      system where the temperature is precisely controlled and monitored at the
      microfluidic channel level. This is realized by integration of a luminescent
      temperature sensor layer into the fluidic structure together with inkjet-printed
      micro heating elements. This allows steering of the temperature at the
      microchannel level and monitoring of the reaction progress simultaneously. A
      fabrication procedure is presented that allows for straightforward integration of
      thin polymer layers with optical sensing functionality in microchannels of glass
      polydimethylsiloxane (PDMS) chips of only 150 MUm width and 29 MUm height. Sensor
      layers consisting of polyacrylonitrile and a temperature-sensitive ruthenium tris
      phenanthroline probe with film thicknesses of about 0.5 to 6 MUm were generated
      by combining blade coating and abrasion techniques. Optimal coating procedures
      were developed and evaluated. The chip-integrated sensor layers were calibrated
      and investigated with respect to stability, reproducibility, and response times.
      These microchips allowed observation of temperature in a wide range with a signal
      change of around 1.6 % per K and a maximum resolution of around 0.07 K. The
      device is employed to study temperature-controlled continuous micro flow
      reactions. This is demonstrated exemplarily for the tryptic cleavage of coumarin
      modified peptides via fluorescence detection. 

PMID- 25377780
TI  - Molecular and cytogenetic evaluation of a patient with ring chromosome 13 and
      discordant results.
AB  - We describe the case of a male newborn with ring chromosome 13 found to have
      dysmorphic features, growth retardation, imperforate anus, and ambiguous
      genitalia. An initial karyotype showed 46,XY,r(13)(p13q34) in the 30 cells
      analyzed. SNP microarray from peripheral blood revealed not only an 8.14-Mb
      13q33.2q34 deletion, but also a duplication of 87.49 Mb suggesting partial
      trisomy 13q that the patient did not appear to have clinically. Further
      cytogenetic characterization detected 3 distinct cell lines in the repeated
      peripheral blood sample: 46,XY,r(13)(p13q34)[89]/
      46,XY,r(13;13)(p13q34)[7]/45,XY,-13[5] and 2 in cultured fibroblasts:
      46,XY,r(13)(p13q34)[65]/45,XY,-13[35]. Repeated molecular studies on peripheral
      blood and fibroblasts, however, failed to document the initially seen partial
      trisomy 13q. We postulate that the presence of duplicated material may be
      evidence of the high burden of duplicate rings in peripheral blood at any given
      time, with the high rates of cell death caused by mitotically unstable double
      rings accounting for the repeated microarray results that failed to detect any
      duplications. We emphasize the correlation between both cytogenetic and molecular
      studies with thorough clinical assessment and suggest that given the high
      sensitivity of newer molecular cytogenetic techniques, careful interpretation of
      results is critical in the context of ring chromosomes.

PMID- 25377781
TI  - Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal
      epithelial tight junctions by dextran sulfate sodium.
AB  - Disruption of intestinal epithelial tight junctions is an important event in the
      pathogenesis of ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis
      in mice with symptoms similar to ulcerative colitis. However, the mechanism of
      DSS-induced colitis is unknown. We investigated the mechanism of DSS-induced
      disruption of intestinal epithelial tight junctions and barrier dysfunction in
      Caco-2 cell monolayers in vitro and mouse colon in vivo. DSS treatment resulted
      in disruption of tight junctions, adherens junctions and actin cytoskeleton
      leading to barrier dysfunction in Caco-2 cell monolayers. DSS induced a rapid
      activation of c-Jun N-terminal kinase (JNK), and the inhibition or knockdown of
      JNK2 attenuated DSS-induced tight junction disruption and barrier dysfunction. In
      mice, DSS administration for 4 days caused redistribution of tight junction and
      adherens junction proteins from the epithelial junctions, which was blocked by
      JNK inhibitor. In Caco-2 cell monolayers, DSS increased intracellular Ca(2+)
      concentration, and depletion of intracellular Ca(2+) by 1,2-bis-(o
      aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)
      (BAPTA/AM) or thapsigargin attenuated DSS-induced JNK activation, tight junction
      disruption and barrier dysfunction. Knockdown of apoptosis signal-regulated
      kinase 1 (Ask1) or MKK7 blocked DSS-induced tight junction disruption and barrier
      dysfunction. DSS activated c-Src by a Ca2+ and JNK-dependent mechanism.
      Inhibition of Src kinase activity or knockdown of c-Src blocked DSS-induced tight
      junction disruption and barrier dysfunction. DSS increased tyrosine
      phosphorylation of occludin, zonula occludens-1 (ZO-1), E-cadherin and beta
      catenin. SP600125 abrogated DSS-induced tyrosine phosphorylation of junctional
      proteins. Recombinant JNK2 induced threonine phosphorylation and auto
      phosphorylation of c-Src. The present study demonstrates that
      Ca(2+)/Ask1/MKK7/JNK2/cSrc signalling cascade mediates DSS-induced tight junction
      disruption and barrier dysfunction.

PMID- 25377782
TI  - Eotaxin-3 (CCL26) exerts innate host defense activities that are modulated by
      mast cell proteases.
AB  - BACKGROUND: During bacterial infections of the airways, a Th1-profiled
      inflammation promotes the production of several host defense proteins and
      peptides with antibacterial activities including beta-defensins, ELR-negative CXC
      chemokines, and the cathelicidin LL-37. These are downregulated by Th2 cytokines
      of the allergic response. Instead, the eosinophil-recruiting chemokines eotaxin
      1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26 are expressed. This study set out
      to investigate whether these chemokines could serve as innate host defense
      molecules during allergic inflammation. METHODS: Antibacterial activities of the
      eotaxins were investigated using viable count assays, electron microscopy, and
      methods assessing bacterial permeabilization. Fragments generated by mast cell
      proteases were characterized, and their potential antibacterial, receptor
      activating, and lipopolysaccharide-neutralizing activities were investigated.
      RESULTS: CCL11, CCL24, and CCL26 all showed potent bactericidal activity,
      mediated through membrane disruption, against the airway pathogens Streptococcus
      pneumoniae, Staphylococcus aureus, Nontypeable Haemophilus influenzae, and
      Pseudomonas aeruginosa. CCL26 retained bactericidal activity in the presence of
      salt at physiologic concentrations, and the region holding the highest
      bactericidal activity was the cationic and amphipathic COOH-terminus. Proteolysis
      of CCL26 by chymase and tryptase, respectively, released distinct fragments of
      the COOH- and NH2 -terminal regions. The COOH-terminal fragment retained
      antibacterial activity while the NH2 -terminal had potent LPS-neutralizing
      properties in the order of CCL26 full-length protein. An identical fragment to
      NH2 -terminal fragment generated by tryptase was obtained after incubation with
      supernatants from activated mast cells. None of the fragments activated the CCR3
      receptor. CONCLUSIONS: Taken together, the findings show that the eotaxins can
      contribute to host defense against common airway pathogens and that their
      activities are modulated by mast cell proteases.

PMID- 25377783
TI  - How I treat poisoning with vitamin K antagonists.
AB  - Severe deficiency of vitamin K-dependent proteins in patients not maintained on
      vitamin K antagonists is most commonly associated with poisoning by or
      surreptitious ingestion of warfarin, warfarin-like anticoagulants, or potent
      rodenticides ("superwarfarins"), such as brodifacoum. Serious bleeding
      manifestations are common. Superwarfarins are 2 orders of magnitude more potent
      than warfarin and have a half-life measured in weeks. These rodenticides are
      readily available household environmental hazards and are sometimes consumed
      accidentally or as manifestations of psychiatric disease. Immediate diagnosis and
      proper therapy is critically important to minimize morbidity and mortality
      because this condition, affecting thousands of patients annually, is reversible.
      Treatment with large doses of oral vitamin K1, often over months to years, to
      maintain a near-normal prothrombin time can reverse the coagulopathy associated
      with superwarfarins. Although these patients initially present to various medical
      specialties, the hematologist is often consulted to offer the definitive
      diagnosis and proper therapy. 

PMID- 25377784
TI  - Deep sequencing identifies genetic heterogeneity and recurrent convergent
      evolution in chronic lymphocytic leukemia.
AB  - Recent high-throughput sequencing and microarray studies have characterized the
      genetic landscape and clonal complexity of chronic lymphocytic leukemia (CLL).
      Here, we performed a longitudinal study in a homogeneously treated cohort of 12
      patients, with sequential samples obtained at comparable stages of disease. We
      identified clonal competition between 2 or more genetic subclones in 70% of the
      patients with relapse, and stable clonal dynamics in the remaining 30%. By deep
      sequencing, we identified a high reservoir of genetic heterogeneity in the form
      of several driver genes mutated in small subclones underlying the disease course.
      Furthermore, in 2 patients, we identified convergent evolution, characterized by
      the combination of genetic lesions affecting the same genes or copy number
      abnormality in different subclones. The phenomenon affects multiple CLL putative
      driver abnormalities, including mutations in NOTCH1, SF3B1, DDX3X, and
      del(11q23). This is the first report documenting convergent evolution as a
      recurrent event in the CLL genome. Furthermore, this finding suggests the
      selective advantage of specific combinations of genetic lesions for CLL
      pathogenesis in a subset of patients. 

PMID- 25377786
TI  - Structural aspects of biological cybernetics: Valentino Braitenberg,
      neuroanatomy, and brain function.

PMID- 25377787
TI  - Correlation between conjunctival and corneal calcification and cardiovascular
      calcification in patients undergoing maintenance hemodialysis.
AB  - The purpose of this study was to investigate the correlation of conjunctival and
      corneal calcification (CCC) with cardiovascular calcification in patients
      undergoing maintenance hemodialysis (MHD). A total of 122 patients undergoing MHD
      in our hospital were included in this study. Conjunctival and corneal
      calcification was examined by slit lamp and graded. Abdominal aortic
      calcification (AAC), aortic valve calcification (AVC), and mitral valve
      calcification (MVC) were determined by X-ray or ultrasound. The correlation of
      CCC with AAC, AVC, and MVC was analyzed. Biochemical, hematological, and
      cardiovascular data were compared between patients with different severity of CCC
      or AAC. Mitral valve calcification was significantly associated with AAC in our
      patients. Conjunctival and corneal calcification positively correlated with AAC.
      We also found that patients with severe CCC exhibited significantly higher levels
      of serum calcium, phosphate, product of calcium and phosphate, serum copper,
      cystatin, intact parathyroid hormone, and vitamin D than patients with mild CCC.
      In addition to significantly increased levels of serum calcium, product of
      calcium and phosphate, serum copper, and cystatin, patients with severe AAC also
      had higher high-sensitivity C-reactive protein level and greater left ventricular
      posterior wall thickness and left ventricular end-diastolic interventricular
      septum thickness than patients with mild AAC. Our results suggest that patients
      undergoing MHD with severe CCC or AAC have high degree of mineral metabolism
      disorder, inflammation, and cardiovascular function disorder. The strong
      correlation between CCC and AAC indicates that CCC score might be used as an
      indirect indicator to predict cardiovascular risks in patients undergoing MHD. 

PMID- 25377785
TI  - High day 28 ST2 levels predict for acute graft-versus-host disease and transplant
      related mortality after cord blood transplantation.
AB  - While cord blood transplantation (CBT) is an effective therapy for hematologic
      malignancies, acute graft-versus-host disease (aGVHD) is a leading cause of
      transplant-related mortality (TRM). We investigated if biomarkers could predict
      aGVHD and TRM after day 28 in CBT recipients. Day 28 samples from 113 CBT
      patients were analyzed. Suppressor of tumorigenicity 2 (ST2) was the only
      biomarker associated with grades II-IV and III-IV aGVHD and TRM. Day 180 grade
      III-IV aGVHD in patients with high ST2 levels was 30% (95% confidence interval
      [CI], 18-43) vs 13% (95% CI, 5-23) in patients with low levels (P = .024). The
      adverse effect of elevated ST2 was independent of HLA match. Moreover, high day
      28 ST2 levels were associated with increased TRM with day 180 estimates of 23%
      (95% CI, 13-35) vs 5% (95% CI, 1-13) if levels were low (P = .001). GVHD was the
      most common cause of death in high ST2 patients. High concentrations of tumor
      necrosis factor receptor-1, interleukin-8, and regenerating islet-derived protein
      3-alpha were also associated with TRM. Our results are consistent with those of
      adult donor allografts and warrant further prospective evaluation to facilitate
      future therapeutic intervention to ameliorate severe aGVHD and further improve
      survival after CBT.

PMID- 25377788
TI  - Narrowband ultraviolet B phototherapy starting and incremental dose in patients
      with psoriasis: comparison of percentage dose and fixed dose protocols.
AB  - BACKGROUND/PURPOSE: It was aimed to investigate the ideal narrowband ultraviolet
      B (NB UVB) phototherapy protocol that has the maximal efficacy, minimal side
      effect profile, minimal cumulative UVB dose, and a shorter duration of therapy.
      METHODS: Fifty-one patients with psoriasis vulgaris were included in the study.
      The patients were divided into the percentage dose (group 1) and the fixed dose
      groups (group 2). In group 1, the initial NB UVB dose was 50% of the minimal
      erythema dose and 20% of the previous dose increase made in the next sessions,
      and in group 2, the starting dose and the dose increases were determined based on
      the skin types and applied with fixed doses. RESULTS: Psoriasis Area and Severity
      Index (PASI) 90 was achieved in 22 out of 27 (81.5%) patients in group 1, and in
      19 out of 24 (79.2%) patients in group 2. The difference was not statistically
      significant (P = 0.82). No statistically significant difference was found between
      the two regimens in the cumulative NB UVB dose, side effect profile, and the
      number of sessions with improvement of the initial PASI score by 90% (for all
      data, P > 0.05). CONCLUSION: These two treatment protocols were not superior to
      each other in terms of cumulative NB UVB dose, efficacy, total number of
      treatment sessions, and side effect profiles.

PMID- 25377789
TI  - Chitosan-templated synthesis of few-layers boron nitride and its unforeseen
      activity as a Fenton catalyst.
AB  - A novel procedure for the preparation of few-layers boron nitride (BN), either as
      films or as suspended BN platelets, is presented, based on the pyrolysis of
      chitosan, which serves both as a matrix to embed ammonium borate and as a
      template for BN synthesis. The resulting BN samples are characterized by XRD,
      Raman and X-ray photoelectron spectroscopy, and by TEM and AFM imaging. The
      samples exhibit deep UV emission, which is characteristic of high quality BN.
      This template synthesis and the easy exfoliation of BN platelets facilitate the
      use of BN as an extremely high-efficiency Fenton catalyst for the generation of
      highly aggressive hydroxyl radicals in water. 

PMID- 25377790
TI  - Separating mixtures by exploiting molecular packing effects in microporous
      materials.
AB  - We examine mixture separations with microporous adsorbents such as zeolites,
      metal-organic frameworks (MOFs) and zeolitic imidazolate frameworks (ZIFs),
      operating under conditions close to pore saturation. Pore saturation is realized,
      for example, when separating bulk liquid phase mixtures of polar compounds such
      as water, alcohols and ketones. For the operating conditions used in industrial
      practice, pore saturation is also attained in separations of hydrocarbon mixtures
      such as xylene isomers and hexane isomers. Separations under pore saturation
      conditions are strongly influenced by differences in the saturation capacities of
      the constituent species; the adsorption is often in favor of the component with
      the higher saturation capacity. Effective separations are achieved by exploiting
      differences in the efficiency with which molecules pack within the ordered
      crystalline porous materials. For mixtures of chain alcohols, the shorter alcohol
      can be preferentially adsorbed because of its higher saturation capacity. With
      hydrophilic adsorbents, water can be selectively adsorbed from water-alcohol
      mixtures. For separations of o-xylene-m-xylene-p-xylene mixtures, the pore
      dimensions of MOFs can be tailored in such a manner as to allow optimal packing
      of the isomer that needs to be adsorbed preferentially. Subtle configurational
      differences between linear and branched alkane isomers result in significantly
      different packing efficiencies within the pore topology of MFI, AFI, ATS, and CFI
      zeolites. A common characteristic feature of most separations that are reliant on
      molecular packing effects is that adsorption and intra-crystalline diffusion are
      synergistic; this enhances the separation efficiencies in fixed bed adsorbers. 

PMID- 25377791
TI  - Axis inhibition protein 2 polymorphisms may be a risk factor for families with
      isolated oligodontia.
AB  - The objective of the present study was to search for Msh homeobox 1 (MSX1),
      paired box gene 9 (PAX9), ectodysplasin-A (EDA) and axis inhibition protein 2
      (AXIN2) variants in a family with isolated oligodontia and analyse the
      pathogenesis of mutations that result in oligodontia phenotypes. Members of a
      single family (but of different descent) with oligodontia and unrelated healthy
      controls were enrolled in our study. Genomic DNA was isolated from blood samples.
      Mutation analysis was performed by amplifying MSX1, PAX9, EDA and AXIN2 exons as
      well as their exon-intron boundaries and sequencing the products. DNA sequencing
      of the AXIN2 gene revealed three mutations in the two patients with oligodontia:
      a homozygotic silent mutation c.1365A>G (p.Pro455=) in exon 3, two c.956+16A>G
      mutations (II-1: homozygosis; III-1: heterozygosis) and c.1200+71A>G
      (homozygosis) in the intron, which possibly contributed to structural and
      functional changes in proteins. The heterozygotic mutations c.1365A>G and
      c.1200+71A>G were identified in the proband's mother (II-2). No mutations were
      detected in the MSX1, PAX9 and EDA genes of oligodontia patients. The findings
      suggest that the c.956+16A>G, c.1365A>G and c.1200+71A>G mutations of AXIN2 may
      be responsible for the oligodontia phenotype in this family, but these findings
      require further study.

PMID- 25377792
TI  - Evaluation of Motor Neuron-Like Cell Differentiation of hEnSCs on Biodegradable
      PLGA Nanofiber Scaffolds.
AB  - Human endometrium is a high-dynamic tissue that contains human endometrial stem
      cells (hEnSCs) which can be differentiated into a number of cell lineages. The
      differentiation of hEnSCs into many cell lineages such as osteoblast, adipocyte,
      and neural cells has been investigated previously. However, the differentiation
      of these stem cells into motor neuron-like cells has not been investigated yet.
      Different biochemical and topographical cues can affect the differentiation of
      stem cells into a specific cell. The aim of this study was to investigate the
      capability of hEnSCs to be differentiated into motor neuron-like cells under
      biochemical and topographical cues. The biocompatible and biodegradable
      poly(lactic-co-glycolic acid) (PLGA) electrospun nanofibrous scaffold was used as
      a topographical cue. Human EnSCs were cultured on the PLGA scaffold and tissue
      culture polystyrene (TCP), then differentiation of hEnSCs into motor neuron-like
      cells under induction media including retinoic acid (RA) and sonic hedgehog (Shh)
      were evaluated for 15 days. The proliferation rate of cells was assayed by using
      MTT assay. The morphology of cells was studied by scanning electron microscopy
      imaging, and the expression of motor neuron-specific markers by real-time PCR and
      immunocytochemistry. Results showed that survival and differentiation of hEnSCs
      into motor neuron-like cells on the PLGA scaffold were better than those on the
      TCP group. Taken together, the results suggest that differentiated hEnSCs on PLGA
      can provide a suitable, three-dimensional situation for neuronal survival and
      outgrowth for regeneration of the central nervous system, and these cells may be
      a potential candidate in cellular therapy for motor neuron diseases.

PMID- 25377793
TI  - Spontaneous and Partial Repair of Ribbon Synapse in Cochlear Inner Hair Cells
      After Ototoxic Withdrawal.
AB  - Ototoxicity is one of the major causes of sensorineural deafness. However, it
      remains unclear whether sensorineural deafness is reversible after ototoxic
      withdrawal. Here, we report that the ribbon synapses between the inner hair cells
      (IHCs) and spiral ganglion nerve (SGN) fibers can be restored after ototoxic
      trauma. This corresponds with hearing restoration after ototoxic withdrawal. In
      this study, adult mice were injected daily with a low dose of gentamicin for 14
      consecutive days. Immunostaining for RIBEYE/CtBP2 was used to estimate the number
      and size of synaptic ribbons in the cochlea. Hearing thresholds were assessed
      using auditory brainstem responses. Auditory temporal processing between IHCs and
      SGNs was evaluated by compound action potentials. We found automatic hearing
      restoration after ototoxicity withdrawal, which corresponded to the number and
      size recovery of synaptic ribbons, although both hearing and synaptic recovery
      were not complete. Thus, our study indicates that sensorineural deafness in mice
      can be reversible after ototoxic withdrawal due to an intrinsic repair of ribbon
      synapse in the cochlea. 

PMID- 25377794
TI  - From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities
      for 5-HT3 Receptor Antagonists.
AB  - 5-HT3 receptor antagonists are extensively used as efficacious agents in
      counteracting chemotherapy-induced emesis. Recent investigations have shed light
      on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some
      studies have reported neuroprotective properties for the 5-HT3 receptor
      antagonists in vitro and in vivo. When administered to Abeta-challenged rat
      cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis,
      elevation of cytosolic Ca(2), glutamate release, reactive oxygen species (ROS)
      generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3
      receptor antagonists possess, alongside their anti-emetic effects, notable
      immunomodulatory properties in CNS. We found that pretreatment with tropisetron
      significantly improved neurological deficits and diminished leukocyte
      transmigration into the brain, TNF-alpha level, and brain infarction in a murine
      model of embolic stroke. Our recent investigation revealed that tropisetron
      protects against Abeta-induced neurotoxicity in vivo through both 5-HT3 receptor
      dependent and -independent pathways. Tropisetron, in vitro, was found to be an
      efficacious inhibitor of the signaling pathway leading to the activation of pro
      inflammatory NF-kappaB, a transcription factor pivotal to the upregulation of
      several neuroinflammatory mediators in brain. This mini review summarizes novel
      evidence concerning effects of 5-HT3 antagonists and their possible mechanisms of
      action in ameliorating neurodegenerative diseases including Alzheimer, multiple
      sclerosis, and stroke. Further, we discuss some newly synthesized 5-HT3 receptor
      antagonists with dual properties of 5-HT3 receptor blockade/alpha-7 nicotinic
      receptor activator and their potential in management of memory impairment. Since
      5-HT3 receptor antagonists possess a large therapeutic window, they can
      constitute a scaffold for design and synthesis of new neuroprotective
      medications. 

PMID- 25377795
TI  - Estradiol and Progesterone Administration After pMCAO Stimulates the Neurological
      Recovery and Reduces the Detrimental Effect of Ischemia Mainly in Hippocampus.
AB  - Epidemiological studies have suggested a differential response, males versus
      female, in stroke incidence and prognosis. These divergences in brain response
      after damage are based mostly on hormonal differences. To date, estradiol and
      progesterone administered independently have demonstrated neuroprotection after
      ischemia in animal models. Nonetheless, contradictory results were revealed using
      a combined administration. In order to evaluate the effects of combinatorial
      treatment administered after ischemia induction, we used two different
      approaches: in vivo and in vitro models. Male rats which underwent permanent
      middle cerebral artery occlusion were treated with a combination of
      estradiol/progesterone at 6, 24 and 48 h after injury and sacrificed at 54 h post
      ischemia. The rat brains were evaluated for reactive gliosis, NeuN-positive
      neurons, levels of synapse-associated proteins and activity levels of
      PI3K/Akt/GSK3/beta-catenin survival pathway. Also, primary cortical neurons were
      subjected to oxygen and glucose deprivation for 17 h and returned to a normal
      environment in the presence of estradiol or estradiol/progesterone. Cell
      viability was evaluated, and activity levels of the PI3K/Akt/GSK3/beta-catenin
      pathway. Our results indicate that some beneficial effects of estradiol were
      abolished in the presence of progesterone, particularly in the cerebral cortex
      (core). However, the combinatorial treatment showed positive effects in the
      hippocampus.

PMID- 25377797
TI  - Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes.
AB  - Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains
      of different molecular weight were assessed for their propensity to undergo
      biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO)
      or ex vivo using freshly isolated primary human neutrophils. Our findings suggest
      that under natural conditions, a combined process of 'stripping' (i.e.,
      defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG
      SWCNTs are a promising--and degradable--nanomedicine vector.

PMID- 25377798
TI  - Fortification of instant coffee beverages - influence of functional ingredients,
      packaging material and storage time on physical properties of newly formulated,
      enriched instant coffee powders.
AB  - BACKGROUND: Consumer demands for healthy, functional foods are growing rapidly
      nowadays. Coffee, as one of the most widespread commodities, represents an
      interesting aspect for enrichment, since it is consumed by millions of people on
      a daily basis. The aim of this study was to formulate enriched instant coffee
      powders with the purpose of estimating the influence of storage time, functional
      ingredients and packaging material on physical and sensory properties of the
      mixtures. RESULTS: Storage time of 6 months significantly (P <0.05) influenced
      moisture content of the mixtures, which rose linearly with an increase in storage
      time. Packaging material proved to be an important variable affecting moisture
      content, particle size, colour and cohesion index. Functional ingredients
      (vitamins A and C, iron, inulin and oligofructose) influenced particle size,
      dispersibility, wettability and, in terms of sensory analysis, grades for
      aftertaste, chemical taste and overall acceptability. CONCLUSION: Addition of
      functional ingredients significantly influenced some particle size distribution
      parameters and reconstitution properties, causing an increase in wettability and
      dispersibility times. Furthermore, in sensory terms, it influenced aftertaste and
      chemical taste grades. Packaging material significantly influenced moisture
      content, some particle size distribution parameters, colour and cohesion index.

PMID- 25377796
TI  - Progranulin Deficiency Reduces CDK4/6/pRb Activation and Survival of Human
      Neuroblastoma SH-SY5Y Cells.
AB  - Null mutations in GRN are associated with frontotemporal lobar degeneration with
      TDP-43 inclusions (FTLD-TDP). However, the influence of progranulin (PGRN)
      deficiency in neurodegeneration is largely unknown. In neuroblastoma cells,
      silencing of GRN gene causes significantly reduced cell survival after serum
      withdrawal. The following observations suggest that alterations of the
      CDK4/6/retinoblastoma protein (pRb) pathway, secondary to changes in PI3K/Akt and
      ERK1/2 activation induced by PGRN deficiency, are involved in the control of
      serum deprivation-induced apoptosis: (i) inhibiting CDK4/6 levels or their
      associated kinase activity by sodium butyrate or PD332991 sensitized control SH
      SY5Y cells to serum deprivation-induced apoptosis without affecting survival of
      PGRN-deficient cells; (ii) CDK4/6/pRb seems to be downstream of the PI3K/Akt and
      ERK1/2 signaling pathways since their specific inhibitors, LY294002 and PD98059,
      were able to decrease CDK6-associated kinase activity and induce death of control
      SH-SY5Y cells; (iii) PGRN-deficient cells show reduced stimulation of PI3K/Akt,
      ERK1/2, and CDK4/6 activities compared with control cells in the absence of
      serum; and (iv) supplementation of recombinant human PGRN was able to rescue
      survival of PGRN-deficient cells. These observations highlight the important role
      of PGRN-mediated stimulation of the PI3K/Akt-ERK1/2/CDK4/6/pRb pathway in
      determining the cell fate survival/death under serum deprivation. 

PMID- 25377799
TI  - Antimicrobial threat.

PMID- 25377800
TI  - Oral health: Risk definition in halitosis.

PMID- 25377801
TI  - Clinical assessment.

PMID- 25377802
TI  - Orthodontics: Misleading focus.

PMID- 25377804
TI  - BDA fights for fair fees and decent regulation.

PMID- 25377803
TI  - SCI-FI dentistry: Are bionic teeth the future?

PMID- 25377806
TI  - Over half of dental nurses have had a needlestick injury.

PMID- 25377809
TI  - New Assistant Editor for BDJ.

PMID- 25377810
TI  - A dentist's life: I never tire of the views in Devon.

PMID- 25377812
TI  - Dental wagon treated soldiers at the front.

PMID- 25377814
TI  - 'A new generation of dental nanomaterials could soon offer enhanced strength and
      caries protection'.
AB  - Dr Michele Barbour is Senior Lecturer in Dental Biomaterials at the University of
      Bristol. Michele's research group is focussed on oral nanoscience, exploiting
      developments in nanotechnology to confer improved antimicrobial and mechanical
      properties on dental and other biomaterials. She is also deputy head of Bristol
      Dental School. 

PMID- 25377815
TI  - Current controversies in training and/or education of dentists in the UK.
AB  - This opinion paper responds to Professor Kay's piece Dental education - shaping
      the future ( 2014; 216: 447-448), arguing that education is not the sole key to
      an innovative future and challenges her view that training discourages free
      thinking. A combination of appropriate training AND education is the sensible
      foundation upon which the future of dentistry can be built. 

PMID- 25377816
TI  - Is dental caries neglect?
AB  - The recent and widespread media interest highlighting the concerning number of
      children with poor oral health has, at last, put paediatric dentistry well and
      truly under the spotlight. Whether on the front page of the Sunday Times
      (http://www.thesundaytimes.co.uk/sto/news/uk_news/Health/Sugar/article1433860.ece
      , on GDPUK forums or live Twitter feeds as ITV's The Dentists was broadcast, the
      whole nation has suddenly awoken to the realisation that tens of thousands of
      children are undergoing multiple dental extractions under general anaesthesia in
      the UK every year. This is of course, not a new phenomenon, so why the sudden
      interest? 

PMID- 25377817
TI  - The role of the general dental practitioner in managing patients who self-harm.
AB  - There has been a reported increase in the incidence of self-harm within the
      United Kingdom. This is of great concern, as a number of studies have shown self
      harm to be a major risk factor to completed suicide. However, the identification
      of self-harm provides an opportunity for support and treatment. Mental health is
      an area that often receives little attention in the undergraduate dental
      curriculum. Yet dental practitioners, as healthcare professionals, need to be
      vigilant for any risk factors or signs of mental illness among their patients and
      make appropriate onward referrals. The purpose of this article is to examine the
      current evidence and aspects of self-harm, particularly in young adults and
      adolescents that are relevant within a dental settling. 

PMID- 25377818
TI  - The restorative management of the deep overbite.
AB  - A deep overbite is where the vertical overlap of the upper and lower incisors
      exceeds half of the lower incisal tooth height. Problems associated with the deep
      overbite can include soft tissue trauma, lack of inter-occlusal space and tooth
      wear, all of which can present significant challenges for the restorative
      dentist. While management options very much depend on the nature of the situation
      and patient's symptoms, options may range from provision of a simple removable
      appliance or splint and non-surgical periodontal therapy, to multidisciplinary
      care involving orthodontics, orthognathic surgery and restorative dentistry.
      Restorative management may involve an increase in the occlusal vertical dimension
      with fixed restorations or removable prostheses, and careful assessment and
      treatment planning is essential. This article discusses the aetiology and
      restorative management strategies for deep and traumatic overbites. 

PMID- 25377819
TI  - Interdisciplinary management of severe intrusion injuries in permanent incisors:
      a case series.
AB  - Intrusion injuries to the permanent dentition are amoung the most severe types of
      dental injuries, occurring in 0.3-1.9% of all dental trauma cases. The current
      clinical guidelines in the management of intrusion injuries are based on level B
      evidence due to the infrequent nature of this type of injury, coupled with a lack
      of high quality evidence-based studies. This paper presents four cases of severe
      intrusion injuries that were successfully managed using an interdisciplinary
      approach. The cases described here highlight the benefits of orthodontic
      repositioning of severely intruded teeth in the short and medium terms. Although
      orthodontic repositioning was unsuccessful in the final case, this did not
      preclude subsequent surgical repositioning. Interdisciplinary collaboration
      allowed two of the cases described to be effectively managed with premolar
      autotransplantation alongside orthodontic treatment. The cases demonstrated here
      indicate the difficulties in providing the current recommended treatment
      modalities at non-specialist clinics. They accentuate the importance of an
      immediate referral of such complex cases to a specialist centre where
      interdisciplinary management is readily available. 

PMID- 25377824
TI  - Summary of: the quality of online information regarding dental implants.

PMID- 25377825
TI  - Summary of: the development and piloting of a leadership questionnaire for
      general dental practitioners: preliminary results from the North West of England
      and Tokyo.

PMID- 25377826
TI  - A school-wide assessment of social media usage by students in a US dental school.
AB  - Social media sites have become an established means of communication due to the
      exponential growth in number of users across the world and the encouragement of
      interaction between users through site features. The purpose of this study was to
      determine the extent to which Loma Linda University School of Dentistry students
      use social media accounts, the types of accounts they prefer, their interest in
      incorporating social media into courses and their perceptions of the usefulness
      of social media in private practice. In addition, we wanted to determine the
      degree of student interest in the integration of these social tools into their
      instruction. One thousand one hundred and sixty-two students from Loma Linda
      University School of Dentistry were invited by e-mail to complete a confidential
      18 item multiple choice survey through Surveymonkey.com. The overall response
      rate was 30% (n = 351) from the pooled response periods; the first in 2011 and
      the second in 2013. Similar to other studies, Facebook was used by 91% of the
      School of Dentistry students, and less than half used Google+, Twitter and
      LinkedIn. Of the respondents, 68% of students reported communicating on social
      media daily and 80% saw value for practising dentists to operate accounts. Time
      and privacy concerns were the largest barriers to usage at 16% and 12%
      respectively. One third of respondents were in favour of the incorporation of
      social media in their courses. 

PMID- 25377827
TI  - 'Dentists' and the establishment of the Anglo-American dental profession in the
      eighteenth century: part 1. The need for a name and an identity.
AB  - This series of papers will examine how the Anglo-American dental profession was
      established in the eighteenth century, examining its need for a name and
      identity, public recognition and official status. This paper outlines the
      evolution of the names of the profession, from tooth-drawer to dentist, and notes
      the importance of the name to the profession. 

PMID- 25377845
TI  - The quality of online information regarding dental implants.
AB  - AIMS AND OBJECTIVES: To analyse the quality of online information available to
      patients regarding dental implants. DESIGN: Cross sectional survey.Setting The
      websites analysed were UK based, owned by private practices and NHS secondary and
      tertiary care services. Information was collated in November 2013. METHODS: UK
      based websites were analysed using UK based search engines.Outcome measures
      Websites were analysed based on content and reliability. Information regarding
      the speciality of authors and accreditation/affiliation to professional
      groups/medical institutions was also collated. RESULTS: Overall, website content
      quality was low, with 63% of sites averaging below 7/14 for their mean summed
      website content scores, and 67% of sites averaging below 8/16 for their mean
      reliability scores. 86.7% were accredited by a recognised national/international
      dental/surgical body but only 26.7% were affiliated to a professional
      group/medical institution. The authors were mainly dentists (73.3%). CONCLUSIONS:
      These findings suggest that the online information regarding implant treatment is
      generally of low quality and many aspects such as long term outcomes and
      complications are overlooked. There is a need for the improvement of the quality
      of online information available to patients in order to make the best use of this
      tool in helping patients to make informed choices about their dental care. The
      Internet has the potential to dramatically change the clinician-patient
      relationship. Moreover, in light of the guidelines produced by the General Dental
      Council (GDC) in 2012 on the principles of ethical advertising, GDC registrants
      run the risk of fitness to practise proceedings and medico-legal challenges if
      the website content has potential to mislead patients.

PMID- 25377846
TI  - The development and piloting of a leadership questionnaire for general dental
      practitioners: preliminary results from the North West of England and Tokyo.
AB  - OBJECTIVES: Key reforms in England and Japan have called for greater clinical
      leadership from general dental practitioners to deliver improvements in the
      quality of care for patients. In England, the reorganisation of the National
      Health Service has led to the development of Local Professional Networks to
      ensure services are clinically led, patient and outcome focused. In Japan, the
      rapidly changing demographics have led to calls for general dental practitioners
      to become more active in meeting the emerging population health challenges. Both
      require engagement at a strategic and a local level. However, little is known
      about what is meant by clinical leadership in dentistry or what training needs
      exist. The aim of this study was to develop and pilot a questionnaire to
      understand what general dental practitioners feel is important about clinical
      leadership and how they rate themselves. METHODS: A 61-item questionnaire was
      developed from the literature, an earlier qualitative study and refined through
      cognitive interviews. Questionnaires were distributed to general dental
      practitioners across the North West of England and Tokyo, using random sequence
      generation. For each item, the participant had to record whether they thought the
      statement was an important component of clinical leadership and how they rated
      themselves. Both were rated using a seven-point Likert scale. Data reduction was
      undertaken using principal component analysis to examine for factor loadings
      within the questionnaire. Differences in mean scores were also used to highlight
      substantive differences in how general dental practitioners rated the different
      components of leadership and how they rated themselves. RESULTS: The response
      rate for the pilot was low (22.9% and 7.5% for North West and Tokyo
      respectively). The items that were considered to be important in leadership
      reduced to two components in the North West (accounting for 62.1% of the total
      variance): 'How to lead' and 'How not to lead'. In Tokyo, 56.4% of the total
      variance was explained by three components: 'Demonstrating personal qualities',
      'Working with others' and 'How not to lead'. When the self-rated items were
      reduced, three factors were found to be important in the North West: 'Working
      with others', 'Setting direction' and 'Managing services' (55.1% of the
      variance). 'Working with others', 'Demonstrating personal qualities',
      'Pragmatism', 'Setting direction' and 'Improving services' were found to be
      important in Tokyo (52.8% of the variance). The questionnaire items relating to
      integrity, team-working and having a positive attitude during difficult times
      were rated highly by both groups. Items relating to providing vision for team,
      being assertive and having a positive attitude had the greatest mean difference,
      suggesting possible areas of training need. CONCLUSION: The nature of the pilot
      study and the poor response rate makes any conclusion difficult to infer. Among
      those that participated, leadership was understood to be more important at a
      practice level rather than at a strategic level. The questionnaire should be
      refined further based on the results of the pilot and the data reduction.

PMID- 25377847
TI  - An equivalence study comparing nitrous oxide and oxygen with low-dose sevoflurane
      and oxygen as inhalation sedation agents in dentistry for adults.
AB  - OBJECTIVE: The aim of this study was to examine whether sevoflurane in oxygen was
      equivalent to near equipotent concentrations of nitrous oxide in oxygen when used
      as an inhalation sedation agent in terms of patient and user acceptability.
      METHOD: Forty anxious dental patients referred to the sedation suite at Cardiff
      University School of Dentistry received either nitrous oxide to a maximum
      concentration of 40% or sevoflurane to a maximum concentration of 0.3% for a
      routine maxillary plastic restoration with articaine infiltration local
      analgesia. The inhalation sedation agent to be administered was chosen by a
      random number allocator. Measurements of blood pressure, oxygen saturation, heart
      rate, respiratory rate and bispectral index were recorded every 5 minutes. At the
      end of the treatment episode the patient, the operator and an observer who was
      unaware of the agent used, recorded their impressions about the episode by
      completing questionnaires. RESULTS: In the doses used in this study, sevoflurane
      was found to be as effective as an inhalation sedation agent as the standard dose
      of nitrous oxide used in normal inhalation sedation in the treatment of adult
      anxious dental patients. CONCLUSION: Sevoflurane in low concentrations is
      equivalent in effect to near equipotent concentrations of nitrous oxide. This
      would suggest that further research, perhaps with slightly higher concentrations
      of sevoflurane, is needed. If sevoflurane was shown to be acceptable at slightly
      higher concentrations, there is scope to explore the development of equipment
      specifically designed to deliver sevoflurane as an inhalation sedation agent in
      future.

PMID- 25377848
TI  - The Populus ARBORKNOX1 homeodomain transcription factor regulates woody growth
      through binding to evolutionarily conserved target genes of diverse function.
AB  - The class I KNOX homeodomain transcription factor ARBORKNOX1 (ARK1) is a key
      regulator of vascular cambium maintenance and cell differentiation in Populus.
      Currently, basic information is lacking concerning the distribution, functional
      characteristics, and evolution of ARK1 binding in the Populus genome. Here, we
      used chromatin immunoprecipitation sequencing (ChIP-seq) technology to identify
      ARK1 binding loci genome-wide in Populus. Computational analyses evaluated the
      distribution of ARK1 binding loci, the function of genes associated with bound
      loci, the effect of ARK1 binding on transcript levels, and evolutionary
      conservation of ARK1 binding loci. ARK1 binds to thousands of loci which are
      highly enriched proximal to the transcriptional start sites of genes of diverse
      functions. ARK1 target genes are significantly enriched in paralogs derived from
      the whole-genome salicoid duplication event. Both ARK1 and a maize (Zea mays)
      homolog, KNOTTED1, preferentially target evolutionarily conserved genes. However,
      only a small portion of ARK1 target genes are significantly differentially
      expressed in an ARK1 over-expression mutant. This study describes the functional
      characteristics and evolution of DNA binding by a transcription factor in an
      undomesticated tree, revealing complexities similar to those shown for
      transcription factors in model animal species. 

PMID- 25377849
TI  - Characterization of the inflammatory response to inhaled lipopolysaccharide in
      mild to moderate chronic obstructive pulmonary disease.
AB  - AIMS: Lipopolysaccharide (LPS) inhalation causes increased airway and systemic
      inflammation. We investigated LPS inhalation in patients with chronic obstructive
      pulmonary disease (COPD) as a model of bacterial exacerbations. We studied
      safety, changes in sputum and systemic biomarkers. We have also investigated
      interleukin (IL)-17 concentrations in this model. METHODS: Twelve COPD patients
      inhaled 5 MUg LPS. Safety was monitored over 24 h. Sputum was induced at
      baseline, 6 and 24 h for cells and IL-8, IL-17, neutrophil elastase, monocyte
      chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP
      1beta) in supernatants. Serum was collected at baseline, 4, 8 and 24 h for IL-6,
      C-reactive protein (CRP) and Clara cell protein (CC-16) concentrations.
      Peripheral blood mononuclear cells (PBMCs) were isolated at baseline and 4 h for
      systemic IL-17 analysis. RESULTS: LPS 5 MUg was well tolerated. The greatest FEV1
      change was 11.7% (mean) at 1 h (95% CI 5.1-18.2%). There was a large range in
      maximal fall (2.5-37.7%). Total sputum cell count and neutrophil count
      significantly increased 6 and 24 h post-LPS. There was no change in sputum
      supernatant mediators. IL-6, CRP and CC-16 increased post-inhalation, with
      different temporal patterns. CD4+ and CD8+ cell associated IL-17 significantly
      increased at 4 h. CONCLUSIONS: Inhaled LPS in COPD patients safely causes
      increased airway and systemic inflammation. This may be a model for studying COPD
      exacerbations.

PMID- 25377851
TI  - A la Fizeau in flow: pulse shape-assisted fluorescence lifetime.

PMID- 25377852
TI  - Predictors of survival outcomes in phase 1 relapsed or refractory multiple
      myeloma patients.
AB  - BACKGROUND: The categories of the International Myeloma Working Group (IMWG)
      response criteria for multiple myeloma are based on the magnitude of the change
      in paraprotein and the normalization of the free light chain ratio (rFLC).
      However, the relationship between the response by these biomarkers and clinical
      outcomes has not been validated with novel compounds in the phase 1 setting.
      Early response predictors may have prognostic value and speed development plans
      for new agents. METHODS: The relationship between biomarkers of response and
      clinical outcomes was examined in 87 relapsed or refractory multiple myeloma
      patients enrolled in nontransplant phase I clinical trials from January 2004
      through November 2011 at 4 time landmarks. Progression-free survival (PFS) was
      the primary outcome, and overall survival (OS) was also assessed. RESULTS: The
      normalization of rFLC within 4 months predicted improvement in PFS (11.3 vs 2.8
      months, P = .038), whereas the normalization of rFLC within 12 months predicted
      improvement in PFS (6.1 vs 2.8 months, P = .015) and OS (45 vs 17.4 months, P =
      .002). The magnitude of response in paraprotein predicted and correlated linearly
      with PFS at all time landmarks (R(2)  = 0.703-0.943) when it was assessed with 2
      different boundaries. CONCLUSIONS: These findings suggest that the normalization
      of rFLC and the magnitude of response are viable biomarkers for surrogate
      endpoints in early-phase clinical trials, validate the use of current IMWG
      response criteria in the phase 1 setting, and support the use of these biomarkers
      for drug development endpoints.

PMID- 25377850
TI  - A systematic review of cost-effectiveness analyses of drugs for postmenopausal
      osteoporosis.
AB  - BACKGROUND: Given the limited availability of healthcare resources and the recent
      introduction of new anti-osteoporosis drugs, the interest in the cost
      effectiveness of drugs in postmenopausal osteoporosis remains and even increases.
      OBJECTIVE: This study aims to identify all recent economic evaluations on drugs
      for postmenopausal osteoporosis, to critically appraise the reporting quality,
      and to summarize the results. METHODS: A literature search using Medline, the
      National Health Service Economic Evaluation database and the Cost-Effectiveness
      Analysis Registry was undertaken to identify original articles published between
      January 1, 2008 and December 31, 2013. Studies that assessed cost effectiveness
      of drugs in postmenopausal osteoporosis were included. The Consolidated Health
      Economic Evaluation Reporting Standards (CHEERS) statement was used to assess the
      quality of reporting of these articles. RESULTS: Of 1,794 articles identified, 39
      studies fulfilled the inclusion criteria. They were conducted in 14 different
      countries and nine active interventions were assessed. When compared with no
      treatment, active osteoporotic drugs were generally cost effective in
      postmenopausal women aged over 60-65 years with low bone mass, especially those
      with prior vertebral fractures. Key drivers of cost effectiveness included
      individual fracture risk, medication adherence, selected comparators and country
      specific analyses. Quality of reporting varied between studies with an average
      score of 17.9 out of 24 (range 7-21.5). CONCLUSION: This review found a
      substantial number of published cost-effectiveness analyses of drugs in
      osteoporosis in the last 6 years. Results and critical appraisal of these
      articles can help decision makers when prioritizing health interventions and can
      inform the development of future economic evaluations.

PMID- 25377853
TI  - Combining region-based and imprecise boundary-based cues for interactive medical
      image segmentation.
AB  - In this paper, we present an approach combining both region selection and user
      point selection for user-assisted segmentation as either an enclosed object or an
      open curve, investigate the method of image segmentation in specific medical
      applications (user-assisted segmentation of the media-adventitia border in
      intravascular ultrasound images, and lumen border in optical coherence tomography
      images), and then demonstrate the method with generic images to show how it could
      be utilized in other types of medical image and is not limited to the
      applications described. The proposed method combines point-based soft constraint
      on object boundary and stroke-based regional constraint. The user points act as
      attraction points and are treated as soft constraints rather than hard
      constraints that the segmented boundary has to pass through. The user can also
      use strokes to specify region of interest. The probabilities of region of
      interest for each pixel are then calculated, and their discontinuity is used to
      indicate object boundary. The combinations of different types of user constraints
      and image features allow flexible and robust segmentation, which is formulated as
      an energy minimization problem on a multilayered graph and is solved using a
      shortest path search algorithm. We show that this combinatorial approach allows
      efficient and effective interactive segmentation, which can be used with both
      open and closed curves to segment a variety of images in different ways. The
      proposed method is demonstrated in the two medical applications, that is,
      intravascular ultrasound and optical coherence tomography images, where image
      artefacts such as acoustic shadow and calcification are commonplace and thus user
      guidance is desirable. We carried out both qualitative and quantitative analysis
      of the results for the medical data; comparing the proposed method against a
      number of interactive segmentation techniques.

PMID- 25377855
TI  - Repairing polymers using oscillating magnetic field.
AB  - Repair of physically separated thermoplastic polymers containing gamma-Fe2 O3
      nanoparticles without sacrificing their mechanical properties is achieved by
      applying an oscillating magnetic field. As gamma-Fe2 O3 nanoparticles oscillate
      at the frequency of the magnetic field, localized amorphous flow occur, and a
      permanent repair of physically separated polymeric films is achieved. 

PMID- 25377856
TI  - What, how and from whom do health care professionals learn during collaboration
      in palliative home care: a cross-sectional study in primary palliative care.
AB  - BACKGROUND: Palliative care often requires inter-professional collaboration,
      offering opportunities to learn from each other. General practitioners often
      collaborate with specialized palliative home care teams. This study seeks to
      identify what, how and from whom health care professionals learn during this
      collaboration. METHODS: Cross-sectional survey in Belgium. All palliative home
      care teams were invited to participate. General practitioners (n = 267) and
      palliative care nurses (n = 73) filled in questionnaires. RESULTS: General
      practitioners (GPs) and palliative care nurses learned on all palliative care
      aspects. Different learning activities were used. Participants learned from all
      others involved in patient care. The professionals' discipline influences the
      content, the way of learning and who learns from whom. Multiple linear regression
      shows significant but limited association of gender with amount of learning by
      GPs (M < F; p = 0.042; Adj R2 = 0.07) and nurses (M > F; p = 0.019; Adj R2 =
      0.01). CONCLUSIONS: This study is the first to reveal what, how and from whom
      learning occurs during collaboration in palliative care. Training professionals
      in sharing expertise during practice and in detecting and adequately responding
      to others' learning needs, could optimize this way of learning.

PMID- 25377857
TI  - Rab2A is a pivotal switch protein that promotes either secretion or ER-associated
      degradation of (pro)insulin in insulin-secreting cells.
AB  - Rab2A, a small GTPase localizing to the endoplasmic reticulum (ER)-Golgi
      intermediate compartment (ERGIC), regulates COPI-dependent vesicular transport
      from the ERGIC. Rab2A knockdown inhibited glucose-stimulated insulin secretion
      and concomitantly enlarged the ERGIC in insulin-secreting cells. Large aggregates
      of polyubiquitinated proinsulin accumulated in the cytoplasmic vicinity of a
      unique large spheroidal ERGIC, designated the LUb-ERGIC. Well-known components of
      ER-associated degradation (ERAD) also accumulated at the LUb-ERGIC, creating a
      suitable site for ERAD-mediated protein quality control. Moreover, chronically
      high glucose levels, which induced the enlargement of the LUb-ERGIC and
      ubiquitinated protein aggregates, impaired Rab2A activity by promoting
      dissociation from its effector, glyceraldehyde-3-phosphate dehydrogenase (GAPDH),
      in response to poly (ADP-ribosyl)ation of GAPDH. The inactivation of Rab2A
      relieved glucose-induced ER stress and inhibited ER stress-induced apoptosis.
      Collectively, these results suggest that Rab2A is a pivotal switch that controls
      whether insulin should be secreted or degraded at the LUb-ERGIC and Rab2A
      inactivation ensures alleviation of ER stress and cell survival under chronic
      glucotoxicity. 

PMID- 25377858
TI  - Is the process for selecting indigents to receive free care in Burkina Faso
      equitable?
AB  - BACKGROUND: In Burkina Faso, patients are required to pay for healthcare. This
      constitutes a barrier to access for indigents, who are the most disadvantaged.
      User fee exemption systems have been created to facilitate their access. A
      community-based initiative was thus implemented in a rural region of Burkina Faso
      to select the worst-off and exempt them from user fees. The final selection was
      not based on pre-defined criteria, but rather on community members' tacit
      knowledge of the villagers. The objective of this study was to analyze the
      equitable nature of this community-based selection process. METHOD: Based on a
      cross-sectional study carried out in 2010, we surveyed 1,687 indigents. The
      variables collected were those that determine healthcare use according to the
      Andersen-Newman model (1969): sociodemographic variables; income; occupation;
      access to financial, food or instrumental assistance; presence of chronic
      illness; and disabilities related to vision, muscle strength, or mobility.
      Bivariate analyses and logistic regression were performed. RESULTS: User fee
      exemptions were given mainly to indigents who were widowed (OR = 1.40; CI 95%
      [1.10-1.78]), had no financial assistance from their household for healthcare (OR
      = 1.58; CI 95% [1.26-1.97], lived alone (OR = 1.28; CI 95% [1.01-1.63]), lived
      with their spouses, (OR = 2.00; CI 95% [1.35-2.96], had vision impairments (OR =
      1.45; CI 95% [1.14-1.84]), or had poor muscle strength and good mobility (OR =
      1.73; CI 95% [1.28-2.33]). The indigent selection was not determined by household
      income, self-reported chronic illness, or previous use of services. CONCLUSION:
      The community selection process took into account factors related to social
      vulnerability and functional limitations. However, we cannot affirm that the
      selection process was perfectly equitable, as it was very restrictive due to the
      limited budget available and the State's lack of engagement in this matter.
      Exemption processes should be temporary solutions, and the State should make a
      commitment to move toward universal healthcare coverage.

PMID- 25377859
TI  - The distribution of doublecortin-immunopositive cells in the brains of four
      afrotherian mammals: the Hottentot golden mole (Amblysomus hottentotus), the rock
      hyrax (Procavia capensis), the eastern rock sengi (Elephantulus myurus) and the
      four-toed sengi (Petrodromus tetradactylus).
AB  - Adult neurogenesis in the mammalian brain is now a widely accepted phenomenon,
      typically occurring in two forebrain structures: the subgranular zone (SGZ) of
      the hippocampal dentate gyrus and the subventricular zone (SVZ). Until recently,
      the majority of studies have focused on laboratory rodents, and it is under
      debate whether the process of adult neurogenesis occurs outside of the SGZ and
      the SVZ in other mammalian species. In the present study, we investigated
      potential adult neurogenetic sites in the brains of two elephant shrews/sengis, a
      golden mole and a rock hyrax, all members of the superorder Afrotheria.
      Doublecortin (DCX) immunoreactivity was used as a proxy to visualise adult
      neurogenesis, which is expressed in neuronal precursor cells and immature
      neurons. In all four species, densely packed DCX-positive cells were present in
      the SVZ, from where cells appear to migrate along the rostral migratory stream
      towards the olfactory bulb (OB). DCX-immunopositive cells were present in the
      granular cell layer and the glomerular layer of the OB. In the hippocampus, DCX
      immunopositive cells were observed in the SGZ and in the granular layer of the
      dentate gyrus, with DCX-immunopositive processes extending into the molecular
      layer. In addition to these well-established adult neurogenic regions, DCX
      immunopositive cells were also observed in layer II of the neocortex and the
      piriform cortex. While the present study reveals a similar pattern of adult
      neurogenesis to that reported previously in other mammals, further studies are
      needed to clarify if the cortical DCX-immunopositive cells are newly generated
      neurons or cells undergoing cortical remodelling.

PMID- 25377860
TI  - Visfatin concentrations in patients with endometrial cancer.
AB  - OBJECTIVE: Visfatin is one of the most recent proteins shown to be highly
      expressed in adipose tissue. The purpose of this study was to determine visfatin
      levels in patients with endometrial cancer (EC). METHODS: A total of 90 patients
      (46 EC patients and 44 healthy controls) were included in the study. Fasting
      venous blood samples were collected from all patients. Serum visfatin levels were
      measured by an enzyme-linked immunosorbent assay (ELISA). The correlation between
      serum visfatin levels and clinicopathologic variables were determined. RESULTS:
      Serum visfatin levels were found to be higher in patients with EC (p < 0.001).
      Visfatin concentrations were positively correlated with age (p = 0.002, r =
      0.323), body mass index (BMI) (p = 0.001, r = 0.354), fasting insulin (p = 0.002,
      r = 0.326), total cholesterol (TC) (p = 0.006, r = 0.285), triglyceride (TG) (p <
      0.001, r = 0.364) levels and homeostasis model-resistance index (HOMA-IR) (p =
      0.007, r = 0.281) of patients. By using classification and regression trees
      (C&RT) method, we found that visfatin predicted patients with EC 100% and
      controls 81.8%. CONCLUSION: Visfatin was the most important risk factor for
      occurrence of EC other than, age, BMI, Diabetes Mellitus and other biochemical
      factors like HDL, LDL, TG, TC. Clearly, there are largely unknown aspects of
      visfatin pathophysiology in EC and require further study.

PMID- 25377862
TI  - Serum Levels of Neurofilament-H are Elevated in Patients Suffering From Severe
      Burns.
AB  - In previous studies, after injury, burn patients experienced an increase in neuro
      inflammation, edema, and neuronal cell death. As demonstrated in other brain
      injury models, fluid-based biomarkers such as phosphorylated neurofilament-H
      (pNFL-H) have been shown to correlate with injury severity. In this study the
      authors hypothesized that burn-injured patients have an increase in pNFL-H in the
      blood during the acute and chronic time-points after injury. In this prospective
      clinical study, blood (8 cc) was collected from burn patients (n = 36; TBSA 10
      60%) at Parkland hospital, Dallas, Texas, on days 1, 7, and 14 after injury. The
      serum levels of pNFL-H were measured using the enzyme-linked immunoassay.
      Compared to noninjured controls, the burn patients exhibited a significant
      increase in the serum levels of pNFL-H on days 7 (P < .0001) and 14 (P < .0001)
      after burn injury. No significant increase was observed on day 1 (P < .07) after
      injury. A positive correlation between TBSA and pNFL-H levels was observed for
      day 14 (r = .55; P < .03). Additionally, using the receiver operating
      characteristic analysis, the authors determined the area under the curve was 98%
      for both day 7 and 14. In conclusion, this study describes the serum profile of
      pNFL-H in patients suffering from severe burns during the acute (day 1) and
      chronic (days 7 and 14) time-points. These results suggest that detection of pNFL
      H may be useful in determining which individuals suffer from nerve cell
      degeneration after burn. 

PMID- 25377861
TI  - ApoE: the role of conserved residues in defining function.
AB  - The amino acid sequences of apolipoprotein E (apoE) from 63 different mammalian
      species have been downloaded from the protein database. The sequences were
      compared to human apoE4 to determine conserved and non-conserved sequences of
      amino acids. ApoE4 is the major risk factor for the development of late onset
      Alzheimer's disease while apoE3, which differs from apoE4 by a single amino acid
      change at position 112, poses little or no risk for the development of this
      disease. Thus, the two proteins appear to be structurally and functionally
      different. Seven highly conserved regions, representing approximately 47 amino
      acids (of 299) have been found. These regions are distributed throughout the
      protein and reflect ligand binding sites as well as regions proposed to be
      involved in the propagation of the cysteine-arginine change at position 112 to
      distant regions of the protein in the N- and C-terminal domains. Highly non
      conserved regions are at the N- and C-terminal ends of the apoE protein. 

PMID- 25377863
TI  - Psychiatric Outcome Over a Decade After Electrical Injury: Depression as a
      Predictor of Long-Term Adjustment.
AB  - Electrical injury (EI) produces a variety of physical, cognitive, and emotional
      consequences. Psychiatric and neurocognitive symptoms may complicate survivors'
      psychosocial adjustment and ability to return to work. However, due to a paucity
      of longitudinal research, the long-term course of EI remains poorly understood.
      The purpose of this study was to investigate psychiatric and functional status in
      EI patients over a decade after injury. Fourteen EI patients who originally
      underwent baseline neuropsychological evaluation participated in this long-term
      follow-up. Participants completed a telephone survey of functional status,
      neuropsychological symptom checklist, and the Psychosocial Adjustment to Illness
      Scale Self-Report. Participants were grouped according to baseline Beck
      Depression Inventory (BDI) scores. After an average of 12.36 years postinjury,
      participants with elevated baseline BDI scores experienced difficulty across
      multiple domains of psychosocial adjustment at follow-up. This group was also
      less likely to return to work and exhibited a significant increase in
      psychological distress. EI results in significant chronic psychiatric complaints
      for many survivors. In the current sample, psychiatric sequelae of EI continue to
      persist over a decade after injury. Moreover, elevated baseline BDI scores
      predicted worse outcomes for vocational and psychosocial adjustment. Findings
      underscore the impact of emotional symptoms on recovery and need for specialized
      psychiatric intervention immediately following injury. 

PMID- 25377864
TI  - Management of Pneumatosis Intestinalis in a Pediatric Burn Patient.
AB  - Pneumatosis intestinalis is gas in the wall of the gastrointestinal tract. It is
      not well described in pediatric burn patients. The authors present the case of a
      23-month-old girl who sustained 40% total body surface area deep-partial and full
      thickness burns as well as a grade two inhalational injury. On postburn day two,
      radiographic imaging showed extensive pneumatosis of the colon. She was managed
      with bowel rest, broad-spectrum antibiotics, and parenteral nutrition.
      Radiographic resolution of pneumatosis intestinalis occurred several days later
      and was followed by reinitiation of enteral feeds and bowel function. The patient
      later developed an abscess and a subsequent colocutaneous fistula that resolved
      with percutaneous drainage and conservative management. She healed and was able
      to avoid a laparotomy with possible bowel resection. 

PMID- 25377865
TI  - First experiences of high-fidelity simulation training in junior nursing students
      in Korea.
AB  - AIM: This study was conducted to explore first experiences of high-fidelity
      simulation training in Korean nursing students, in order to develop and establish
      more effective guidelines for future simulation training in Korea. METHODS:
      Thirty-three junior nursing students participated in high-fidelity simulation
      training for the first time. Using both qualitative and quantitative methods,
      data were collected from reflective journals and questionnaires of simulation
      effectiveness after simulation training. Descriptive statistics were used to
      analyze simulation effectiveness and content analysis was performed with the
      reflective journal data. RESULTS: Five dimensions and 31 domains, both positive
      and negative experiences, emerged from qualitative analysis: (i) machine-human
      interaction in a safe environment; (ii) perceived learning capability; (iii)
      observational learning; (iv) reconciling practice with theory; and (v) follow-up
      debriefing effect. More than 70% of students scored high on increased ability to
      identify changes in the patient's condition, critical thinking, decision-making,
      effectiveness of peer observation, and debriefing in effectiveness of simulation.
      CONCLUSION: This study reported both positive and negative experiences of
      simulation. The results of this study could be used to set the level of task
      difficulty in simulation. Future simulation programs can be designed by
      reinforcing the positive experiences and modifying the negative results.

PMID- 25377866
TI  - A dyadic approach: applying a developmental-conceptual model to couples coping
      with chronic illness.
AB  - The purpose of the present study was to apply Berg and Upchurch's developmental
      conceptual model toward a better understanding of how couples cope with chronic
      illness. Specifically, a model was hypothesized in which proximal factors
      (relational quality), dyadic appraisal (illness interference), and dyadic coping
      (partner support) influence adjustment (health condition management). The study
      was cross-sectional and included 308 dyads in which one partner has a chronic
      health condition. The actor partner interdependence model shows how congruence
      and noncongruence in relational quality, dyadic appraisal, and dyadic coping
      influence dyadic adjustment. 

PMID- 25377867
TI  - On the anatomy of the 'hook' region of the human cochlea and how it relates to
      cochlear implantation.
AB  - BACKGROUND: The optimal insertion route for an electrode array in hearing
      preservation cochlear implantation (CI) surgery is still tentative. Both
      cochleostomy (CO) and round window (RW) techniques are used today. In the present
      study we analyzed size variations and topographic anatomy of the 'hook' region of
      the human cochlea to better comprehend the Testo effects of various electric
      array insertion modes. MATERIAL AND METHODS: Size variations of the cochlear
      'hook' region were assessed in 23 human, microdissected temporal bones by
      measuring the distances between the oval and round windows, also outlining the
      spiral ligament/spiral lamina. Influence of size variations on spiral ligament
      position and fundamentals for different surgical approaches were evaluated in a
      subset of 'small' and 'large' cochleae performing different types of CO. In
      addition, the relationship between the microdissected accessory canal housing the
      inferior cochlear vein and the RW was analyzed. RESULTS: The lateral vestibular
      wall and the cochlear 'hook' displayed large anatomic variations that greatly
      influenced the size of the potential surgical area. RESULTS showed that only very
      inferiorly located CO entered the scala tympani without causing trauma to the
      spiral ligament and spiral lamina. An inferior approach may challenge the
      inferior cochlear vein. CONCLUSION: Preoperative assessment of the distance
      between the round and oval windows may direct the surgeon before CI hearing
      preservation surgery. CO techniques, especially in 'small' ears, may lead to
      frequent damage to the inner ear structures. In those cases with substantial
      residual hearing, CI surgery may be better performed through a RW approach.

PMID- 25377868
TI  - Dehalococcoides mccartyi strain JNA dechlorinates multiple chlorinated phenols
      including pentachlorophenol and harbors at least 19 reductive dehalogenase
      homologous genes.
AB  - Pentachlorophenol and other chlorinated phenols are highly toxic ubiquitous
      environmental pollutants. Using gas chromatographic analysis we determined that
      Dehalococcoides mccartyi strain JNA in pure culture dechlorinated
      pentachlorophenol to 3,5-dichlorophenol (DCP) via removal of the ortho and para
      chlorines in all of the three possible pathways. In addition, JNA dechlorinated
      2,3,4,6-tetrachlorophenol via 2,4,6-trichlorophenol (TCP) and 2,4,5-TCP to 2,4
      DCP and 3,4-DCP, respectively, and dechlorinated 2,3,6-TCP to 3-chlorophenol (CP)
      via 2,5-DCP. JNA converted 2,3,4-TCP to 3,4-DCP and 2,4-DCP by ortho and meta
      dechlorination, respectively. 2,3-DCP was dechlorinated to 3-CP, and, because
      cultures using it could be transferred with a low inoculum (0.5 to 1.5% vol/vol),
      it may act as an electron acceptor to support growth. Using PCR amplification
      with targeted and degenerate primers followed by cloning and sequencing, we
      determined that JNA harbors at least 19 reductive dehalogenase homologous (rdh)
      genes including orthologs of pcbA4 and pcbA5, pceA, and mbrA, but not tceA or
      vcrA. Many of these genes are shared with D. mccartyi strains CBDB1, DCMB5, GT,
      and CG5. Strain JNA has previously been shown to extensively dechlorinate the
      commercial polychlorinated biphenyl (PCB) mixture Aroclor 1260. Collectively the
      data suggest that strain JNA may be well adapted to survive in sites contaminated
      with chlorinated aromatics and may be useful for in situ bioremediation. 

PMID- 25377870
TI  - High-resolution patterning of graphene by screen printing with a silicon stencil
      for highly flexible printed electronics.
AB  - High-resolution screen printing of pristine graphene is introduced for the rapid
      fabrication of conductive lines on flexible substrates. Well-defined silicon
      stencils and viscosity-controlled inks facilitate the preparation of high-quality
      graphene patterns as narrow as 40 MUm. This strategy provides an efficient method
      to produce highly flexible graphene electrodes for printed electronics. 

PMID- 25377869
TI  - Localization of alpha-adrenoceptors: JR Vane Medal Lecture.
AB  - This review is based on the JR Vane Medal Lecture presented at the BPS Winter
      Meeting in December 2011 by J.C. McGrath. A recording of the lecture is included
      as supporting information. It covers his laboratory's work from 1990 to 2010 on
      the localization of vascular alpha1 -adrenoceptors in native tissues, mainly
      arteries. MAIN POINTS: (i) alpha1 -adrenoceptors are present on several cell
      types in arteries, not only on medial smooth muscle, but also on adventitial,
      endothelial and nerve cells; (ii) all three receptor subtypes (alpha1 A , alpha1
      B , alpha1 D ) are capable of binding ligands at the cell surface, strongly
      indicating that they are capable of function and not merely expressed. (iii) all
      of these cell types can take up an antagonist ligand into the intracellular
      compartments to which endocytosing receptors move; (iv) each individual subtype
      can exist at the cell surface and intracellularly in the absence of the other
      subtypes. As functional pharmacological experiments show variations in the
      involvement of the different subtypes in contractions of different arteries, it
      is concluded that the presence and disposition of alpha1 -adrenoceptors in
      arteries is not a simple guide to their involvement in function. Similar
      locations of the subtypes, even in different cell types, suggest that differences
      between the distribution of subtypes in model systems do not directly correlate
      with those in native tissues. This review includes a historical summary of the
      alternative terms used for adrenoceptors (adrenergic receptors, adrenoreceptors)
      and the author's views on the use of colours to illustrate different items, given
      his partial colour-blindness.

PMID- 25377871
TI  - Identification of linear B-cell epitopes within Tarp of Chlamydia trachomatis.
AB  - Chlamydia trachomatis is one of the most prevalent sexually transmitted
      pathogens. There is currently no commercially available vaccine against C.
      trachomatis. Chlamydial translocated actin-recruiting phosphoprotein (Tarp) can
      induce cellular and humoral immune responses in murine models and has been
      regarded as a potential vaccine candidate. In this report, the amino acid
      sequence of Tarp was analyzed using computer-assisted techniques to scan B-cell
      epitopes, and six possible linear B-cell epitopes peptides (aa80-95, aa107-123,
      aa152-170, aa171-186, aa239-253 and aa497-513) with high predicted antigenicity
      and high conservation were investigated. Sera from mice immunized with these
      potential immunodominant peptides was analyzed by ELISA, which showed that
      epitope 152-170 elicited serum immunoglobulin G (IgG) response and epitope 171
      186 elicited both serum IgG and mucosal secretory immunoglobulin A response. The
      response of immune sera of epitope 171-186 to endogenous Tarp antigen obtained
      from the Hela229 cells infected with C. trachomatis was confirmed by Western blot
      and indirect fluorescence assay. In addition, binding of the antibodies against
      epitope 171-186 to endogenous Tarp was further confirmed by competitive ELISA.
      Our results demonstrated that the putative epitope (aa171-186) was an
      immunodominant B-cell epitope of Tarp. If proven protective and safe, this
      epitope, in combination with other well-documented epitopes, might be included
      into a candidate epitope-based vaccine against C. trachomatis.

PMID- 25377872
TI  - Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863)
      failed to improve measures of performance in subjects with claudication-limited
      peripheral artery disease.
AB  - Hypoxia inducible factor (HIF) stabilization by HIF-prolyl hydroxylase (PHD)
      inhibitors may improve ischemic conditions such as peripheral artery disease
      (PAD). This multicenter, randomized, placebo-controlled study evaluated the
      safety and efficacy of GSK1278863 (an oral PHD inhibitor) in subjects with PAD.
      The study assessed two active treatment paradigms: single dosing and subchronic
      daily dosing (300 mg single dose and 15 mg daily for 14 days, respectively).
      Neither regimen improved exercise performance compared with placebo (change from
      baseline in the 6-minute walk test (6MWT; feet), (GSK1278863, placebo): single
      dose (-46, -44), p=0.96; repeat dose (9, 8), p=0.99; change in number of
      contractions to onset of claudication (goniometry): single dose (4, -1), p=0.053;
      repeat dose (-2, 1), p=0.08). A calf-muscle biopsy substudy showed no increases
      in mRNA or protein levels of HIF target genes. More subjects receiving GSK1278863
      than placebo experienced adverse events, particularly following the 300 mg single
      dose. Thus, assessing the safety of GSK1278863 in this setting would require a
      larger population exposed to the agent for a longer duration. These data do not
      support a benefit of GSK1278863 in PAD using the regimens tested.
      CLINICALTRIALSGOV IDENTIFIER NCT01673555: 

PMID- 25377873
TI  - Effect of microelectrode structure on electrocatalysis at nucleic acid-modified
      sensors.
AB  - The electrochemical detection of nucleic acids using an electrocatalytic reporter
      system and nanostructured microelectrodes is a powerful approach to
      ultrasensitive biosensing. In this report we systematically study for the first
      time the behavior of an electrocatalytic reporter system at nucleic acid-modified
      electrodes with varying structures and sizes. [Ru(NH3)6](3+) is used as a primary
      electron acceptor that is electrostatically attracted to nucleic acid-modified
      electrodes, and [Fe(CN)6](3-) is introduced into the redox system as a secondary
      electron acceptor to regenerate Ru(3+) after electrochemical reduction. We found
      that the electrode structure has strong impact on mass transport and electron
      transfer kinetics, with structures of specific dimensions yielding much higher
      electrochemical signals and catalytic efficiencies. The electrocatalytic signals
      obtained when gold sensors were electrodeposited in both circular and linear
      apertures were studied, and the smallest structures plated in linear apertures
      were found to exhibit the best performance with high current densities and
      turnover rates. This study provides important information for optimal assay
      performance and insights for the future design and fabrication of high
      performance biomolecular assays. 

PMID- 25377874
TI  - Nanoparticle-mediated binning and profiling of heterogeneous circulating tumor
      cell subpopulations.
AB  - The analysis of circulating tumor cells (CTCs) is an important capability that
      may lead to new approaches for cancer management. CTC capture devices developed
      to date isolate a bulk population of CTCs and do not differentiate subpopulations
      that may have varying phenotypes with different levels of clinical relevance.
      Here, we present a new device for CTC spatial sorting and profiling that
      sequesters blood-borne tumor cells with different phenotypes into discrete
      spatial bins. Validation data are presented showing that cancer cell lines with
      varying surface expression generate different binning profiles within the device.
      Working with patient blood samples, we obtain profiles that elucidate the
      heterogeneity of CTC populations present in cancer patients and also report on
      the status of CTCs within the epithelial-to-mesenchymal transition (EMT). 

PMID- 25377875
TI  - In vivo pancreatic beta-cell-specific expression of antiaging gene Klotho: a
      novel approach for preserving beta-cells in type 2 diabetes.
AB  - Protein expression of an antiaging gene, Klotho, was depleted in pancreatic
      islets in patients with type 2 diabetes mellitus (T2DM) and in db/db mice, an
      animal model of T2DM. The objective of this study was to investigate whether in
      vivo expression of Klotho would preserve pancreatic beta-cell function in db/db
      mice. We report for the first time that beta-cell-specific expression of Klotho
      attenuated the development of diabetes in db/db mice. beta-Cell-specific
      expression of Klotho decreased hyperglycemia and enhanced glucose tolerance. The
      beneficial effects of Klotho were associated with significant improvements in
      T2DM-induced decreases in number of beta-cells, insulin storage levels in
      pancreatic islets, and glucose-stimulated insulin secretion from pancreatic
      islets, which led to increased blood insulin levels in diabetic mice. In
      addition, beta-cell-specific expression of Klotho decreased intracellular
      superoxide levels, oxidative damage, apoptosis, and DNAJC3 (a marker for
      endoplasmic reticulum stress) in pancreatic islets. Furthermore, beta-cell
      specific expression of Klotho increased expression levels of Pdx-1 (insulin
      transcription factor), PCNA (a marker of cell proliferation), and LC3 (a marker
      of autophagy) in pancreatic islets in db/db mice. These results reveal that beta
      cell-specific expression of Klotho improves beta-cell function and attenuates the
      development of T2DM. Therefore, in vivo expression of Klotho may offer a novel
      strategy for protecting beta-cells in T2DM. 

PMID- 25377876
TI  - Adipocyte pseudohypoxia suppresses lipolysis and facilitates benign adipose
      tissue expansion.
AB  - Prolyl hydroxylase enzymes (PHDs) sense cellular oxygen upstream of hypoxia
      inducible factor (HIF) signaling, leading to HIF degradation in normoxic
      conditions. In this study, we demonstrate that adipose PHD2 inhibition plays a
      key role in the suppression of adipocyte lipolysis. Adipose Phd2 gene ablation in
      mice enhanced adiposity, with a parallel increase in adipose vascularization
      associated with reduced circulating nonesterified fatty acid levels and normal
      glucose homeostasis. Phd2 gene-depleted adipocytes exhibited lower basal
      lipolysis in normoxia and reduced beta-adrenergic-stimulated lipolysis in both
      normoxia and hypoxia. A selective PHD inhibitor suppressed lipolysis in murine
      and human adipocytes in vitro and in vivo in mice. PHD2 genetic ablation and
      pharmacological inhibition attenuated protein levels of the key lipolytic
      effectors hormone-sensitive lipase and adipose triglyceride lipase (ATGL),
      suggesting a link between adipocyte oxygen sensing and fatty acid release. PHD2
      mRNA levels correlated positively with mRNA levels of AB-hydrolase domain
      containing-5, an activator of ATGL, and negatively with mRNA levels of lipid
      droplet proteins, perilipin, and TIP47 in human subcutaneous adipose tissue.
      Therapeutic pseudohypoxia caused by PHD2 inhibition in adipocytes blunts
      lipolysis and promotes benign adipose tissue expansion and may have therapeutic
      applications in obesity or lipodystrophy. 

PMID- 25377877
TI  - TLR2- and Dectin 1-associated innate immune response modulates T-cell response to
      pancreatic beta-cell antigen and prevents type 1 diabetes.
AB  - The progression of autoimmune diseases is dictated by deviations in the fine
      balance between proinflammatory versus regulatory responses, and pathogen
      recognition receptors (PRRs) play a key role in maintaining this balance.
      Previously, we have reported that ligation of Toll-like receptor 2 (TLR2) and
      Dectin 1 on antigen-presenting cells by zymosan results in a regulatory immune
      response that prevents type 1 diabetes (T1D). Here, we show that TLR2 and Dectin
      1 engagement by zymosan promotes regulatory T-cell (Treg) responses against the
      pancreatic beta-cell-specific antigen (Ag). Unlike the TLR4 ligand, bacterial
      lipopolysaccharide, which induced proinflammatory cytokines and pathogenic T
      cells, zymosan induced a mixture of pro- and anti-inflammatory factors and Tregs,
      both in vitro and in vivo. Ag-specific T cells that are activated using zymosan
      exposed dendritic cells (DCs) expressed Foxp3 and produced large amounts of IL
      10, TGF-beta1, and IL-17. NOD mice that received beta-cell-Ag-loaded, zymosan
      exposed DCs showed delayed hyperglycemia. Injection of NOD mice at the
      prediabetic age and early hyperglycemic stage with beta-cell-Ag, along with
      zymosan, results in a superior protection of the NOD mice from diabetes as
      compared with mice that received zymosan alone. This therapeutic effect was
      associated with increased frequencies of IL-10-, IL-17-, IL-4-, and Foxp3
      positive T cells, especially in the pancreatic lymph nodes. These results show
      that zymosan can be used as an immune regulatory adjuvant for modulating the T
      cell response to pancreatic beta-cell-Ag and reversing early-stage hyperglycemia
      in T1D. 

PMID- 25377879
TI  - Differential effects of type and quantity of leaf damage on growth, reproduction
      and defence of lima bean (Phaseolus lunatus L.).
AB  - Folivores are major plant antagonists in most terrestrial ecosystems. However,
      the quantitative effects of leaf area loss on multiple interacting plant traits
      are still little understood. We sought to contribute to filling this lack of
      understanding by applying different types of leaf area removal (complete leaflets
      versus leaflet parts) and degrees of leaf damage (0, 33 and 66%) to lima bean
      (Phaseolus lunatus) plants. We quantified various growth and fitness parameters
      including above- and belowground biomass as well as the production of
      reproductive structures (fruits, seeds). In addition, we measured plant
      cyanogenic potential (HCNp; direct chemical defence) and production of
      extrafloral nectar (EFN; indirect defence). Leaf damage reduced above- and
      belowground biomass production in general, but neither variation in quantity nor
      type of damage resulted in different biomass. Similarly, the number of fruits and
      seeds was significantly reduced in all damaged plants without significant
      differences between treatment groups. Seed mass, however, was affected by both
      type and quantity of leaf damage. Leaf area loss had no impact on HCNp, whereas
      production of EFN decreased with increasing damage. While EFN production was
      quantitatively affected by leaf area removal, the type of damage had no effect.
      Our study provides a thorough analysis of the quantitative and qualitative
      effects of defoliation on multiple productivity-related and defensive plant
      traits and shows strong differences in plant response depending on trait.
      Quantifying such plant responses is vital to our understanding of the impact of
      herbivory on plant fitness and productivity in natural and agricultural
      ecosystems. 

PMID- 25377878
TI  - Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of
      the mTORC2-Akt signaling.
AB  - Sestrin proteins have been implicated in multiple biological processes including
      resistance to oxidative and genotoxic stresses, protection against aging-related
      pathologies, and promotion of metabolic homeostasis; however, the underlying
      mechanisms are incompletely understood. Some evidence suggests that sestrins may
      inhibit mTORC1 (mechanistic target of rapamycin complex 1) through inhibition of
      RagA/B GTPases or activation of AMPK; however, whether sestrins are also involved
      in mTORC2 regulation and function is unclear. To investigate the functions and
      mechanisms of Sestrin 3 (Sesn3), we generated Sesn3 liver-specific transgenic and
      knockout mice. Our data show that Sesn3 liver-specific knockout mice exhibit
      insulin resistance and glucose intolerance, and Sesn3 transgenic mice were
      protected against insulin resistance induced by a high-fat diet. Using AMPK liver
      specific knockout mice, we demonstrate that the Sesn3 insulin-sensitizing effect
      is largely independent of AMPK. Biochemical analysis reveals that Sesn3 interacts
      with and activates mTORC2 and subsequently stimulates Akt phosphorylation at
      Ser473. These findings suggest that Sesn3 can activate Akt via mTORC2 to regulate
      hepatic insulin sensitivity and glucose metabolism. 

PMID- 25377880
TI  - Asthma: the role of low high-density-lipoprotein cholesterol in childhood and
      adolescence.
AB  - BACKGROUND: Several studies have examined the relationship of asthma with serum
      dyslipidemia and reported positive, negative or no association. Most studies were
      limited by their cross-sectional design and the wide age range of the
      participants. In a cohort of children in Cyprus, we explored the association of
      asthma with serum high-density-lipoprotein cholesterol (HDL-C) at age 16-18 years
      (follow-up) independently of and in relation to HDL-C at age 11-12 years
      (baseline). METHODS: In a case-control design, we recruited active asthmatics
      (AA; n = 68), current wheezers only (CWO; n = 123) and non-asthmatic controls (n
      = 660). Logistic regression models were used to evaluate associations of asthma
      with follow-up serum HDL-C and the role of baseline HDL-C. RESULTS: At follow-up,
      mean HDL-C levels in AA and CWO patients were significantly lower than in the
      controls (47.9 and 49.7 vs. 53.4 mg/dl; p = 0.001 and p = 0.011). We observed
      significant associations of AA patients with low HDL-C (<15th percentile; OR
      2.32, 95% CI 1.16-4.47) that remained significant after further adjustment for
      baseline HDL-C (OR 2.14, 95% CI 1.06-4.14). Stratification by baseline HDL-C
      indicated that the association was significant only in those with high baseline
      HDL-C (OR 2.40, 95% CI 1.03-5.20). Stratification by IgE sensitization showed
      that the association was pronounced only in subjects who were sensitized (OR
      3.41, 95% CI 1.12-9.88). CONCLUSIONS: Adolescent asthma is associated with low
      serum HDL-C independent of previous HDL-C levels in childhood. The association
      appears pronounced in those with a drop in HDL-C levels between childhood and
      adolescence and in those who have IgE sensitization.

PMID- 25377881
TI  - Effect of nitric oxide on spinal evoked potentials and survival rate in rats with
      decompression sickness.
AB  - Nitric oxide (NO) releasing agents have, in experimental settings, been shown to
      decrease intravascular nitrogen bubble formation and to increase the survival
      rate during decompression sickness (DCS) from diving. The effect has been
      ascribed to a possible removal of preexisting micronuclei or an increased
      nitrogen washout on decompression through augmented blood flow rate. The present
      experiments were conducted to investigate whether a short- or long-acting NO
      donor [glycerol trinitrate (GTN) or isosorbide-5-mononitrate (ISMN),
      respectively] would offer the same protection against spinal cord DCS evaluated
      by means of spinal evoked potentials (SEPs). Anesthetized rats were decompressed
      from a 1-h hyperbaric air dive at 506.6 kPa (40 m of seawater) for 3 min and 17
      s, and spinal cord conduction was studied by measurements of SEPs. Histological
      samples of the spinal cord were analyzed for lesions of DCS. In total, 58 rats
      were divided into 6 different treatment groups. The first three received either
      saline (group 1), 300 mg/kg iv ISMN (group 2), or 10 mg/kg ip GTN (group 3)
      before compression. The last three received either 300 mg/kg iv ISMN (group 4), 1
      mg/kg iv GTN (group 5), or 75 MUg/kg iv GTN (group 6) during the dive, before
      decompression. In all groups, decompression caused considerable intravascular
      bubble formation. The ISMN groups showed no difference compared with the control
      group, whereas the GTN groups showed a tendency toward faster SEP disappearance
      and shorter survival times. In conclusion, neither a short- nor long-acting NO
      donor had any protective effect against fatal DCS by intravenous bubble
      formation. This effect is most likely due to a fast ascent rate overriding the
      protective effects of NO, rather than the total inert tissue gas load. 

PMID- 25377882
TI  - Physiology in Medicine: physiological basis of diaphragmatic dysfunction with
      abdominal hernias-implications for therapy.
AB  - An incisional hernia is a common complication after abdominal surgery. Complaints
      of dyspnea in this population may be attributed to cardiopulmonary dysfunction or
      deconditioning. Large abdominal incisional hernias, however, may cause diaphragm
      dysfunction and result in dyspnea, which is more pronounced when standing
      (platypnea). The use of an abdominal binder may alleviate platypnea in this
      population. We discuss the link between diaphragm dysfunction and the lack of
      abdominal wall integrity and how abdominal wall support partially restores
      diaphragm function. 

PMID- 25377883
TI  - Effect of induced leg muscle fatigue on exertional dyspnea in healthy subjects.
AB  - The genesis of dyspnea is complex. It appears to be related to central
      respiratory drive although prevailing leg fatigue could independently potentiate
      dyspnea. We hypothesized that experimentally induced leg fatigue generates more
      intense exertional dyspnea for a given level of ventilatory drive. Following
      familiarization, 19 healthy subjects (32.2 +/- 7.6 yr; 11 men) performed a 5-min
      treadmill test (speed: ~4 km/h; grade: ~25%) on two separate days randomized
      between control (C) and experimentally induced leg fatigue (E) achieved by
      repeated knee extension against 40% body weight until task failure. Oxygen uptake
      (Vo2, l/min), carbon dioxide output (Vco2, l/min), ventilation (Ve, l/min), and
      respiratory rate (fR) were measured breath by breath. Heart rate (HR) and
      perceived dyspnea intensity (0-10 numerical scale) were recorded continuously.
      Data were averaged over 30-s intervals. Exertional dyspnea during E was
      statistically significantly higher (E vs. C: 4.2 +/- 0.2 vs. 3.4 +/- 0.2, P <
      0.001) and accompanied by a significant increase in Ve (E vs. C: 61.7 +/- 3.7 vs.
      55.3 +/- 2.8, P = 0.005) and fR (E vs. C: 26.7 +/- 1.0 vs. 24.2 +/- 1.3, P =
      0.036). Dyspnea following E remained significantly higher after allowing for the
      Ve confound (ANCOVA, P = 0.003). Vo2, Vco2, and HR were not significantly
      different between two conditions. However, the slopes for dyspnea vs. Vo2 and
      dyspnea vs. Ve were similar between E and C, which suggested that gain in dyspnea
      per unit change in Vo2 or Ve was not altered by leg fatigue. These findings
      support the hypothesis that the intensity of exertional dyspnea is exacerbated by
      peripheral afferent information from fatigued leg muscles. 

PMID- 25377885
TI  - Parabiotic model for differentiating local and systemic effects of continuous and
      intermittent hypoxia.
AB  - Hypoxia can be damaging either because cells are directly sensitive to low oxygen
      pressure in their local microenvironment and/or because they are exposed to
      circulating factors systemically secreted in response to hypoxia. The
      conventional hypoxia model, breathing hypoxic air, does not allow one to
      distinguish between these local and systemic effects. Here we propose and
      validate a model for differentially applying local and systemic hypoxic
      challenges in an animal. We used parabiosis, two mice sharing circulation by
      surgical union through the skin, and tested the hypothesis that when one of the
      parabionts breathes room air and the other one is subjected to hypoxic air, both
      mice share systemic circulation but remain normoxic and hypoxic, respectively. We
      tested two common hypoxic paradigms in 10 parabiotic pairs: continuous hypoxia
      (10% O2) mimicking chronic lung diseases, and intermittent hypoxia (40 s, 21% O2;
      20 s, 5% O2) simulating sleep apnea. Arterial oxygen saturation and oxygen
      partial pressure at muscle tissue were measured in both parabionts. Effective
      cross-circulation was assessed by intraperitoneally injecting a dye in one of the
      parabionts and measuring blood dye concentration in both animals after 2 h. The
      results confirmed the hypothesis that tissues of the parabiont under room air
      were perfused with normally oxygenated blood and, at the same time, were exposed
      to all of the systemic mediators secreted by the other parabiont actually
      subjected to hypoxia. In conclusion, combination of parabiosis and
      hypoxic/normoxic air breathing is a novel approach to investigate the effects of
      local and systemic hypoxia in respiratory diseases. 

PMID- 25377884
TI  - Sodium nitrite supplementation improves motor function and skeletal muscle
      inflammatory profile in old male mice.
AB  - Aging is associated with motor declines that lead to functional limitations and
      disability, necessitating the development of therapies to slow or reverse these
      events. We tested the hypothesis that sodium nitrite supplementation attenuates
      declines in motor function in older C57BL/6 mice. Motor function was assessed
      using a battery of tests (grip strength, open-field distance, rota-rod endurance)
      in old animals (age 20-24 mo) at baseline and after 8 wk of sodium nitrite (old
      nitrite, n = 22, 50 mg/liter) or no treatment (old control, n = 40), and in young
      reference animals (3 mo, n = 87). Eight weeks of sodium nitrite supplementation
      improved grip strength (old nitrite, +12.0 +/- 14.9% vs. old control, +1.5 +/-
      15.2%, P < 0.05) and open field distance (old nitrite, +9.5 +/- 7.7%, P < 0.01
      vs. old control, -28.1 +/- 2.0%) and completely restored rota-rod endurance-run
      time (old nitrite, +3.2 +/- 7.1%, P < 0.01 vs. old control, -21.5 +/- 7.2%; old
      nitrite after treatment P > 0.05 vs. young reference). Inflammatory cytokines
      were markedly increased in quadriceps of old compared with young reference
      animals (by ELISA, interleukin-1beta [IL-1beta] 3.86 +/- 2.34 vs. 1.11 +/- 0.74,
      P < 0.05; interferon-gamma [INF-gamma] 8.31 +/- 1.59 vs. 3.99 +/- 2.59, P < 0.01;
      tumor necrosis factor-alpha [TNF-alpha] 1.69 +/- 0.44 vs. 0.76 +/- 0.30 pg/ml, P
      < 0.01), but were reduced to young reference levels after treatment (old nitrite,
      IL-1beta 0.67 +/- 0.95; INF-gamma 5.22 +/- 2.01, TNF-alpha 1.21 +/- 0.39 pg/ml, P
      < 0.05 vs. old control, P > 0.05 vs. young reference). Cytokine expression and
      treatment (old nitrite vs. old control) predicted strength (R(2) = 0.822, P <
      0.001, IL-1beta, INF-gamma, group), open field distance (R(2) = 0.574, P < 0.01,
      IL-1beta, group) and endurance run time (R(2) = 0.477, P < 0.05, INF-gamma). Our
      results suggest that sodium nitrite improves motor function in old mice, in part
      by reducing low-grade inflammation in muscle. 

PMID- 25377886
TI  - Interstitial high-dose rate brachytherapy as boost for anal canal cancer.
AB  - AIM: To assess clinical outcomes of patients treated with a high-dose rate
      brachytherapy boost for anal canal cancer (ACC). METHODS: From August 2005 to
      February 2013, 28 patients presenting an ACC treated by split-course external
      beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a
      French regional cancer center in Nice were retrospectively analyzed. RESULTS:
      Median age was 60.6 years [34 - 83], 25 patients presented a squamous cell
      carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT
      was 45 Gy [43.2 - 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with
      a median duration of 2 days. Median overall treatment time was 63 days and median
      delay between EBRT and brachytherapy was 20 days. Two-year local relapse free,
      metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and
      87.7% respectively. Acute toxicities were frequent but not severe with mostly
      grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of
      cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two
      year colostomy-free survival was 75.1%, one patient had a definitive sphincter
      amputation. CONCLUSION: High-dose rate brachytherapy for anal canal carcinoma as
      boost represents a feasible technique compared to low or pulsed-dose rate
      brachytherapy. This technique remains an excellent approach to precisely boost
      the tumor in reducing the overall treatment time.

PMID- 25377887
TI  - Myocardial performance index in fetal anemia.
AB  - OBJECTIVE: The objective of the study was to examine the correlation between
      fetal myocardial performance index (MPI) and hemoglobin (Hb) levels. METHODS: It
      is a prospective study involving singleton pregnancies at risk of fetal anemia as
      a result of maternal anti-D alloimmune disease. Right and left ventricle (LV)
      MPIs were evaluated by ultrasound up to 72 h before cordocentesis. Zeta-score
      values for fetal MPI and Hb levels were calculated, and correlation was examined
      with linear regression analysis. Significance level was set as 0.05. RESULTS:
      Fourteen singleton pregnancies underwent 31 cordocentesis procedures at a mean
      gestation of 28.2 +/- 4.1 weeks. Zeta-score values for LV MPI, isovolumetric
      relaxation time (IRT), and ejection time (ET) correlated significantly with fetal
      Hb zeta-score (LV MPI zeta = 3.816 + 0.336 * Hb zeta, r = 0.59, p < 0.001; LV IRT
      zeta = 2.643 + 0.218 * Hb zeta, r = 0.45, p = 0.01; LV ET zeta = -2.474 - 0.271 *
      Hb zeta, r = -0.42, p = 0.02). LV isovolumetric contraction time (ICT) zeta-score
      and right ventricle (RV) MPI did not show significant correlation (LV ICT zeta, r
      = 0.35, p = 0.054; RV MPI, r = 0.12, p = 0.53). CONCLUSION: LV myocardial
      performance not only remains preserved but also is actually enhanced in cases of
      moderate/severe fetal anemia.

PMID- 25377888
TI  - C9orf72 repeat expansions in rapid eye movement sleep behaviour disorder.
AB  - BACKGROUND: A large hexanucleotide repeat expansion in C9orf72 has been
      identified as the most common genetic cause in familial amyotrophic lateral
      sclerosis and frontotemporal dementia. Rapid Eye Movement Sleep Behavior Disorder
      (RBD) is a sleep disorder that has been strongly linked to synuclein-mediated
      neurodegeneration. The aim of this study was to evaluate the role of the C9orf72
      expansions in the pathogenesis of RBD. METHODS: We amplified the C9orf72 repeat
      expansion in 344 patients with RBD by a repeat-primed polymerase chain reaction
      assay. RESULTS: We identified two RBD patients carrying the C9orf72 repeat
      expansion. Most interestingly, these patients have the same C9orf72 associated
      risk haplotype identified in 9p21-linked amyotrophic lateral sclerosis and
      frontotemporal dementia families. CONCLUSIONS: Our study enlarges the phenotypic
      spectrum associated with the C9orf72 hexanucleotide repeat expansions and
      suggests that, although rare, this expansion may play a role in the pathogenesis
      of RBD.

PMID- 25377889
TI  - Lassa and Marburg viruses elicit distinct host transcriptional responses early
      after infection.
AB  - BACKGROUND: Lassa virus and Marburg virus are two causative agents of viral
      hemorrhagic fever. Their diagnosis is difficult because patients infected with
      either pathogen present similar nonspecific symptoms early after infection.
      Current diagnostic tests are based on detecting viral proteins or nucleic acids
      in the blood, but these cannot be found during the early stages of disease,
      before the virus starts replicating in the blood. Using the transcriptional
      response of the host during infection can lead to earlier diagnoses compared to
      those of traditional methods. RESULTS: In this study, we use RNA sequencing to
      obtain a high-resolution view of the in vivo transcriptional dynamics of
      peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We
      report a subset of host mRNAs, including heat-shock proteins like HSPA1B,
      immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose
      differences in expression are strong enough to distinguish Lassa infection from
      Marburg infection in non-human primates. We have validated these infection
      specific expression differences by using microarrays on a larger set of samples,
      and by quantifying the expression of individual genes using RT-PCR. CONCLUSIONS:
      These results suggest that host transcriptional signatures are correlated with
      specific viral infections, and that they can be used to identify highly
      pathogenic viruses during the early stages of disease, before standard detection
      methods become effective.

PMID- 25377890
TI  - Clinical structural anatomy of the inferior pyramidal space reconstructed from
      the living heart: Three-dimensional visualization using multidetector-row
      computed tomography.
AB  - The inferior pyramidal space (IPS) comprises the epicardial visceral adipose
      tissue wedged between the bottoms of the four cardiac chambers from the postero
      inferior epicardial surface of the heart. Understanding the complex anatomy
      around the IPS is important for clinical cardiologists. Although leading
      anatomists and radiologists have clarified the anatomy of the IPS in detail, few
      studies have demonstrated this anatomy in three dimensions. The aim of this study
      was to visualize the three-dimensional anatomy of the IPS reconstructed from the
      living heart using multidetector-row computed tomography. We also developed an
      original paper model of the IPS to enhance understanding of its intricate
      structure.

PMID- 25377892
TI  - A reliable and time-saving semiautomatic spike-template-based analysis of
      interictal EEG-fMRI.
AB  - OBJECTIVE: A prerequisite for the implementation of interictal
      electroencephalography-correlated functional magnetic resonance imaging (EEG
      fMRI) in the presurgical work-up for epilepsy surgery is straightforward
      processing. We propose a new semi-automatic method as alternative for the
      challenging and time-consuming visual spike identification. METHODS: Our method
      starts from a patient-specific spike-template, built by averaging spikes recorded
      on the EEG outside the scanner. Spatiotemporal cross-correlations between the
      template and the EEG measured during fMRI were calculated. To minimize false
      positive detections, this time course of cross-correlations was binarized by
      means of a spike-template-specific threshold determined in healthy controls. To
      inform our model for statistical parametric mapping, this binarized regressor was
      convolved with the canonical hemodynamic response function. We validated our
      "template-based" method in 21 adult patients with refractory focal epilepsy with
      a well-defined epileptogenic zone and interictal spikes during EEG-fMRI.
      Sensitivity and specificity for detecting the epileptogenic zone were calculated
      and represented in receiver operating characteristic (ROC) curves. Our approach
      was compared with a previously proposed semiautomatic "topography-based" method
      that used the topographic amplitude distribution of spikes as a starting point
      for correlation-based fitting. RESULTS: Good diagnostic performance could be
      reached with our template-based method. The optimal area under the ROC curve was
      0.77. Diagnostic performance of the topography-based method was overall low.
      SIGNIFICANCE: Our new template-based method is more standardized and time-saving
      than visual spike identification on intra-scanner EEG recordings, and preserves
      good diagnostic performance for detecting the epileptogenic zone.

PMID- 25377891
TI  - Mechanistic determinants of the directionality and energetics of active export by
      a heterodimeric ABC transporter.
AB  - The ATP-binding cassette (ABC) transporter associated with antigen processing
      (TAP) participates in immune surveillance by moving proteasomal products into the
      endoplasmic reticulum (ER) lumen for major histocompatibility complex class I
      loading and cell surface presentation to cytotoxic T cells. Here we delineate the
      mechanistic basis for antigen translocation. Notably, TAP works as a molecular
      diode, translocating peptide substrates against the gradient in a strict
      unidirectional way. We reveal the importance of the D-loop at the dimer interface
      of the two nucleotide-binding domains (NBDs) in coupling substrate translocation
      with ATP hydrolysis and defining transport vectoriality. Substitution of the
      conserved aspartate, which coordinates the ATP-binding site, decreases NBD
      dimerization affinity and turns the unidirectional primary active pump into a
      passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not
      required for translocation per se, but is essential for both active and
      unidirectional transport. Our data provide detailed mechanistic insight into how
      heterodimeric ABC exporters operate. 

PMID- 25377893
TI  - Missing semantic annotation in databases. The root cause for data integration and
      migration problems in information systems.
AB  - Data integration is a well-known grand challenge in information systems. It is
      highly relevant in medicine because of the multitude of patient data sources.
      Semantic annotations of data items regarding concept and value domain, based on
      comprehensive terminologies can facilitate data integration and migration.
      Therefore it should be implemented in databases from the very beginning. 

PMID- 25377894
TI  - Insights into the posttranslational assembly of the Mo-, S- and Cu-containing
      cluster in the active site of CO dehydrogenase of Oligotropha carboxidovorans.
AB  - Oligotropha carboxidovorans is characterized by the aerobic chemolithoautotrophic
      utilization of CO. CO oxidation by CO dehydrogenase proceeds at a unique
      bimetallic [CuSMoO2] cluster which matures posttranslationally while integrated
      into the completely folded apoenzyme. Kanamycin insertional mutants in coxE, coxF
      and coxG were characterized with respect to growth, expression of CO
      dehydrogenase, and the type of metal center present. These data along with
      sequence information were taken to delineate a model of metal cluster assembly.
      Biosynthesis starts with the MgATP-dependent, reductive sulfuration of [Mo(VI)O3]
      to [Mo(V)O2SH] which entails the AAA+-ATPase chaperone CoxD. Then Mo(V) is
      reoxidized and Cu(1+)-ion is integrated. Copper is supplied by the soluble CoxF
      protein which forms a complex with the membrane-bound von Willebrand protein CoxE
      through RGD-integrin interactions and enables the reduction of CoxF-bound Cu(2+),
      employing electrons from respiration. Copper appears as Cu(2+)-phytate, is
      mobilized through the phytase activity of CoxF and then transferred to the CoxF
      putative copper-binding site. The coxG gene does not participate in the
      maturation of the bimetallic cluster. Mutants in coxG retained the ability to
      utilize CO, although at a lower growth rate. They contained a regular CO
      dehydrogenase with a functional catalytic site. The presence of a pleckstrin
      homology (PH) domain on CoxG and the observed growth rates suggest a role of the
      PH domain in recruiting CO dehydrogenase to the cytoplasmic membrane enabling
      electron transfer from the enzyme to the respiratory chain. CoxD, CoxE and CoxF
      combine motifs of a DEAD-box RNA helicase which would explain their mutual
      translation. 

PMID- 25377895
TI  - Computational evidence for structural consequences of kiteplatin damage on DNA.
AB  - The reaction of the potential anticancer drug kiteplatin, cis-[PtCl2(cis-1,4
      DACH)], with oligomers of single- and double-stranded DNA ranging from 2 to 12
      base pairs in length was performed as a model for DNA interaction. The potential
      for conformational flexibility of single-stranded adducts was examined with
      density functional theory (DFT) and compared with data from (1)H-NMR 1D and 2D
      spectroscopy. This indicates the presence of multiple conformations of an adduct
      with d(GpG), but only one form of the adduct with d(TGGT). The importance of a
      suitable theoretical model, and in particular basis set, in reproducing
      experimental data is demonstrated. The DFT theoretical model was extended to
      platinated base pair step (GG/CC), allowing a comparison to the related compounds
      cisplatin and oxaliplatin. Adducts of kiteplatin with larger fragments of double
      stranded DNA, including tetramer, octamer, and dodecamer, were studied
      theoretically using hybrid quantum mechanics/molecular mechanics methods.
      Structural parameters of all the base-paired models were evaluated and binding
      energies calculated in gas phase and in solution; these are compared across the
      series and also with the related complexes cisplatin and oxaliplatin, thus
      revealing insights into how kiteplatin binds to DNA and similarities and
      differences between this and related compounds. 

PMID- 25377896
TI  - Metastatic ovarian carcinoma to the brain: an approach to identification and
      classification for neuropathologists.
AB  - Brain metastasis is an uncommon but increasing manifestation of ovarian
      epithelial carcinoma and neuropathologists' collective experience with these
      tumors is limited. We present clinicopathological characteristics of 13 cases of
      brain metastases from ovarian epithelial carcinoma diagnosed at two academic
      institutions. The mean ages at diagnosis of the ovarian carcinoma and their
      subsequent brain metastases were 58.7 and 62.8 years, respectively. At the time
      of initial diagnosis of ovarian carcinoma the majority of patients had an
      advanced stage and none had brain metastases as their first manifestation of
      malignancy. Brain metastases tended to be multiple with ring-enhancing features
      on neuroimaging. Primary tumors and their brain metastases were all high-grade
      histologically and the histologic subtypes were: nine high-grade serous carcinoma
      (HGSC) cases, two clear cell carcinoma (CCC) cases and a single case each of
      carcinosarcoma and high-grade adenocarcinoma. A recommended histo- and
      immunopathological approach to these tumours are provided to aid
      neuropathologists in the recognition and classification of metastatic ovarian
      carcinoma to the brain.

PMID- 25377897
TI  - Heterogeneous bone marrow uptake on interim 18F-fluorodeoxyglucose positron
      emission tomography for lymphoma mimicking disease progression: a case report.
AB  - INTRODUCTION: The use of 18F-fluorodeoxyglucose positron emission tomography (18F
      FDG PET) scanning for baseline staging and assessment of treatment response for
      higher grade lymphomas is considered to be the standard of care. Evaluation of
      lymphomatous bone marrow infiltration on 18F-FDG PET can usually distinguish
      between normal regenerating marrow following chemotherapy by a characteristic
      pattern of uptake. CASE PRESENTATION: Here we report the case of a 51-year-old
      Caucasian woman with mixed low- and high-grade lymphoma with biopsy confirmed
      marrow infiltration. An interim post-three cycle chemotherapy 18F-FDG PET scan
      revealed apparent progression of marrow disease. Subsequent investigations were
      performed including bone marrow biopsies, repeat 18F-FDG PET scanning and a white
      cell scan. These revealed the interim 18F-FDG PET scan appearance was due to a
      highly unusual pattern of scattered islands of regenerating normal marrow, rather
      than progressive lymphoma. CONCLUSIONS: Our case report highlights that apparent
      severe bone marrow abnormalities on 18F-FDG PET scans in lymphoma patients
      treated with chemotherapy are not always due to disease. Clinicians should retain
      a high index of suspicion for benign causes when 18F-FDG PET scan results appear
      incongruent with clinical response.

PMID- 25377901
TI  - Foraging behaviour of the parasitoid Eretmocerus eremicus under intraguild
      predation risk by Macrolophus pygmaeus.
AB  - BACKGROUND: Intraguild predation (IGP), predation between species that use a
      common resource, can affect the populations of a pest, of the pest's natural
      enemy (IG prey) and of the predator of the pest's natural enemy (IG predator). In
      this study, we determined whether the parasitoid Eretmocerus eremicus
      (Hymenoptera: Aphelinidae) (IG prey), modifies its foraging behaviour under the
      risk of IGP by Macrolophus pygmaeus (Hemiptera: Miridae) (IG predator).
      Parasitoid behaviour was analysed using two bioassays (choice and no-choice) with
      the following treatments: (i) control, tomato leaf infested with whitefly nymphs;
      and (ii) PEP, tomato leaf infested with whitefly nymphs and previously exposed to
      the IG predator; and (iii) PP, tomato leaf infested with whitefly nymphs, with
      both, the IG predator and the IG prey present. RESULTS: In both bioassays, we
      found that E. eremicus did not significantly modify the number of ovipositions,
      time of residence, duration of oviposition or behavioural sequence. However, in
      the no-choice bioassay, the number of attacks was higher and their duration
      shorter in the PEP treatment than in the control. CONCLUSION: Our results
      indicate that the parasitoid may detect IGP risk to a certain extent, but it did
      not significantly modify its foraging behaviour, suggesting that simultaneous
      release of the two natural enemies can be successfully employed.

PMID- 25377899
TI  - Identification of antipsychotic drug fluspirilene as a potential p53-MDM2
      inhibitor: a combined computational and experimental study.
AB  - The inhibition of tumor suppressor p53 protein due to its direct interaction with
      oncogenic murine double minute 2 (MDM2) protein, plays a central role in almost
      50 % of all human tumor cells. Therefore, pharmacological inhibition of the p53
      binding pocket on MDM2, leading to p53 activation, presents an important
      therapeutic target against these cancers expressing wild-type p53. In this
      context, the present study utilized an integrated virtual and experimental
      screening approach to screen a database of approved drugs for potential p53-MDM2
      interaction inhibitors. Specifically, using an ensemble rigid-receptor docking
      approach with four MDM2 protein crystal structures, six drug molecules were
      identified as possible p53-MDM2 inhibitors. These drug molecules were then
      subjected to further molecular modeling investigation through flexible-receptor
      docking followed by Prime/MM-GBSA binding energy analysis. These studies
      identified fluspirilene, an approved antipsychotic drug, as a top hit with MDM2
      binding mode and energy similar to that of a native MDM2 crystal ligand. The
      molecular dynamics simulations suggested stable binding of fluspirilene to the
      p53-binding pocket on MDM2 protein. The experimental testing of fluspirilene
      showed significant growth inhibition of human colon tumor cells in a p53
      dependent manner. Fluspirilene also inhibited growth of several other human tumor
      cell lines in the NCI60 cell line panel. Taken together, these computational and
      experimental data suggest a potentially novel role of fluspirilene in inhibiting
      the p53-MDM2 interaction. It is noteworthy here that fluspirilene has a long
      history of safe human use, thus presenting immediate clinical potential as a
      cancer therapeutic. Furthermore, fluspirilene could also serve as a structurally
      novel lead molecule for the development of more potent, small-molecule p53-MDM2
      inhibitors against several types of cancer. Importantly, the combined
      computational and experimental screening protocol presented in this study may
      also prove useful for screening other commercially-available compound databases
      for identification of novel, small molecule p53-MDM2 inhibitors. 

PMID- 25377898
TI  - Ghrelin signalling on food reward: a salient link between the gut and the
      mesolimbic system.
AB  - 'Hunger is the best spice' is an old and wise saying that acknowledges the fact
      that almost any food tastes better when we are hungry. The neurobiological
      underpinnings of this lore include activation of the brain's reward system and
      the stimulation of this system by the hunger-promoting hormone ghrelin. Ghrelin
      is produced largely from the stomach and levels are higher preprandially. The
      ghrelin receptor is expressed in many brain areas important for feeding control,
      including not only the hypothalamic nuclei involved in energy balance regulation,
      but also reward-linked areas such as the ventral tegmental area. By targeting the
      mesoaccumbal dopamine neurones of the ventral tegmental area, ghrelin recruits
      pathways important for food reward-related behaviours that show overlap with but
      are also distinct from those important for food intake. We review a variety of
      studies that support the notion that ghrelin signalling at the level of the
      mesolimbic system is one of the key molecular substrates that provides a
      physiological signal connecting gut and reward pathways. 

PMID- 25377902
TI  - Collaboration amongst clinical nursing leadership teams: a mixed-methods
      sequential explanatory study.
AB  - AIM: To explore intra-professional collaboration amongst nursing leadership teams
      at a tertiary referral hospital in Sydney. BACKGROUND: Effective working within a
      wide network of alliances is critical to patient outcomes. An understanding of
      collaboration amongst nursing leadership teams is essential within this context.
      METHODS: A sequential explanatory mixed-methods design was used. The
      Collaborative Behaviour scale was sent to 106 Nurse Unit Managers, Nurse
      Educators and Clinical Nurse Consultants to measure pairwise collaborative
      behaviours; two follow-up focus groups with 15 participants were conducted. Data
      were collected between May 2012 and May 2013. A thematic analysis of focus group
      data provided a detailed explanation of the questionnaire findings. RESULTS: The
      findings identified high collaboration between dyad groups. Two themes emerged
      from the thematic analysis: (1) professional role and expectations; with sub
      themes of transparency and clarity of individual roles; and intra/interpersonal
      aspects of role functioning; and (2) organisational infrastructure and
      governance. CONCLUSION: These leadership teams can be effective and powerful
      vehicles for change and are central to optimum patient outcomes. Organisational
      strategic planning and evaluation can benefit from understanding how to promote
      collaborative behaviours in these nurse leaders. IMPLICATIONS FOR NURSING
      MANAGEMENT: To date, little research has explored collaboration amongst nursing
      leadership teams. Successful collaboration may contribute to the efficient use of
      nursing resources; improve patient outcomes, and ultimately, nurse satisfaction
      and retention.

PMID- 25377903
TI  - Evaluating catheter complications and outcomes in patients receiving home
      parenteral nutrition.
AB  - RATIONALE, AIMS AND OBJECTIVES: We describe catheter complications and outcomes
      in patients who received home parenteral nutrition (HPN) therapy. METHODS:
      Retrospective chart data were obtained from Boston Home Infusion agency that
      provided HPN therapy to 212 patients [International Classification of Diseases,
      9th revision (ICD-9) codes: gastrointestinal (GI)-related disorders and oncology]
      between 1 January 2005 and 30 September 2011. RESULTS: Of the 163 patients who
      represented 19104 home-catheter days, 19 (11.7%) patients experienced 25 catheter
      complications (CCs; 12 occlusions, 11 central line-associated bloodstream
      infections, one thrombosis and one line dislodgment). The overall CC rate was
      1.30 per 1000 peripherally inserted central catheter (PICC)-line days. The mean
      number of PICC-line days (278.7 +/- 335.0 vs. 95.9 +/- 154.0) and patients with
      at least one hospital admission were significantly higher for patients with one
      or more CCs compared with patients with no CCs (P<0.03). CONCLUSION: Patients who
      experienced CCs had more PICC-line days, more hospital admissions and had an ICD
      9 code for GI-related disorders compared with patients with oncology-related
      diagnoses.

PMID- 25377904
TI  - Consulting with children in the development of self-efficacy and recall tools
      related to nutrition and physical activity.
AB  - PURPOSE: This article chronicles our efforts to develop an instrument with and
      for children-complete with insights, multiple iterations, and missteps along the
      way. The instruments we developed assess children's self-efficacy and recall
      related to healthy eating and physical activity. DESIGN AND METHODS: Five focus
      groups were held with 39 children to discuss the evolving instrument. RESULTS: A
      nine-item self-efficacy instrument and a 10-item recall instrument were developed
      with Flesch-Kincaid grade levels of 1.8 and 4.0, respectively, which fifth
      graders can complete in less than 5 min. PRACTICE IMPLICATIONS: When assessing
      children in clinical practice or research, we should use instruments that have
      been developed with children's feedback and are child-centered. Without that
      assurance, assessment results can be questionable.

PMID- 25377906
TI  - Gaucher disease and bone manifestations.
AB  - Gaucher disease is a relatively rare metabolic disease caused by the inherited
      deficiency of the lysosomal enzyme glucocerebrosidase. Gaucher disease affects
      multiple organs, among which is the skeleton. Bone involvement occurs frequently
      in Gaucher disease, and is one of its most debilitating features, reducing the
      quality of life of patients. Bone status is an important consideration for
      treatment to ameliorate symptoms and reduce the risk of irreversible
      complications. We have conducted a systematic review of all the various aspects
      of Gaucher disease, focusing on different skeletal manifestations,
      pathophysiology of bone alterations, clinical symptoms, and current diagnostic
      and therapeutic approaches. 

PMID- 25377905
TI  - Aptamer CaCO3 nanostructures: a facile, pH-responsive, specific platform for
      targeted anticancer theranostics.
AB  - The application of cancer theranostics depends on the development of
      multifunctional nanostructured platforms for accurate cell targeting and
      controlled drug release, imaging, and therapy. Herein, a comprehensive, easily
      fabricated anticancer theranostic platform with a high drug-loading capacity,
      termed an aptamer-functionalized calcium carbonate (CaCO3 ) nanostructure (apt
      CCN), is reported. Flow cytometry and confocal fluorescence microscopy studies
      demonstrate that apt-CCNs can specifically bind to target cancer cells, but not
      to control cells, and that they possess highly efficient internalization to
      target cancer cells. This smart nanostructure selectively reaches the lysosomes
      through receptor-mediated endocytosis and is responsive to the relatively low
      lysosome pH (4.5-5.5), which facilitates the release of doxorubicin. The apt-CCN
      platform offers targeted and efficient drug transport, as well as target-specific
      delivery of imaging agents for cancer diagnosis and therapy. 

PMID- 25377907
TI  - Increased bone mineral density with monthly intravenous ibandronate contributes
      to fracture risk reduction in patients with primary osteoporosis: three-year
      analysis of the MOVER study.
AB  - The relationship between gains in bone mineral density (BMD) in the hip and the
      incidence of vertebral fractures in the MOVER study was examined. Japanese
      patients from the ibandronate and risedronate treatment groups whose hip BMD had
      increased during the 3-year treatment period were classified into those with or
      without vertebral fractures. In both the ibandronate group and the risedronate
      group, hip BMD gains in the patients who had developed no vertebral fractures
      during the treatment period were greater than in the patients who developed
      vertebral fractures. We categorized the gains in hip BMD at 6 months into 3
      groups (<=0, >0 to <=3, and >3%), and used logistic regression analysis to
      estimate odds ratios and the probabilities of incidence of vertebral fractures at
      12, 24, and 36 months. The current study demonstrated that greater gains in hip
      BMD during the first 6 months of treatment were associated with a reduction in
      the risk of subsequent vertebral fractures during the duration of treatment, and
      suggested that measurement of hip BMD gain at that time could lead to a
      prediction of the risk of the future vertebral fracture incidence.

PMID- 25377908
TI  - Guideline for the acquisition and preparation of conventional and endobronchial
      ultrasound-guided transbronchial needle aspiration specimens for the diagnosis
      and molecular testing of patients with known or suspected lung cancer.
AB  - RATIONALE: Conventional transbronchial needle aspiration (TBNA) and endobronchial
      ultrasound (EBUS)-TBNA are widely accepted tools for the diagnosis and staging of
      lung cancer and the initial procedure of choice for staging. Obtaining adequate
      specimens is key to provide a specific histologic and molecular diagnosis of lung
      cancer. OBJECTIVES: To develop practice guidelines on the acquisition and
      preparation of conventional TBNA and EBUS-TBNA specimens for the diagnosis and
      molecular testing of (suspected) lung cancer. We hope to improve the global
      unification of procedure standards, maximize the yield and identify areas for
      research. METHODS: Systematic electronic database searches were conducted to
      identify relevant studies for inclusion in the guideline [PubMed and the Cochrane
      Library (including the Cochrane Database of Systematic Reviews)]. MAIN RESULTS:
      The number of needle aspirations with both conventional TBNA and EBUS-TBNA was
      found to impact the diagnostic yield, with at least 3 passes needed for optimal
      performance. Neither needle gauge nor the use of miniforceps, the use of suction
      or the type of sedation/anesthesia has been found to improve the diagnostic yield
      for lung cancer. The use of rapid on-site cytology examination does not increase
      the diagnostic yield. Molecular analysis (i.e. EGFR, KRAS and ALK) can be
      routinely performed on the majority of cytological samples obtained by EBUS-TBNA
      and conventional TBNA. There does not appear to be a superior method for specimen
      preparation (i.e. slide staining, cell blocks or core tissue). It is likely that
      optimal specimen preparation may vary between institutions depending on the
      expertise of pathology colleagues.

PMID- 25377909
TI  - Effector cell signature in peripheral blood following nasal allergen challenge in
      grass pollen allergic individuals.
AB  - BACKGROUND: Several studies have demonstrated the time course of inflammatory
      mediators in nasal fluids following nasal allergen challenge (NAC), whereas the
      effects of NAC on cells in the periphery are unknown. We examined the time course
      of effector cell markers (for basophils, dendritic cells and T cells) in
      peripheral blood after nasal grass pollen allergen challenge. METHODS: Twelve
      participants with seasonal allergic rhinitis underwent a control (diluent)
      challenge followed by NAC after an interval of 14 days. Nasal symptoms and peak
      nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T
      cell and dendritic cell responses (flow cytometry), T-cell proliferative
      responses (thymidine incorporation), and cytokine expression (FluoroSpot assay).
      RESULTS: Robust increases in nasal symptoms and decreases in PNIF were observed
      during the early (0-1 h) response and modest significant changes during the late
      (1-24 h) response. Sequential peaks in peripheral blood basophil activation
      markers were observed (CD107a at 3 h, CD63 at 6 h, and CD203c(bright) at 24 h). T
      effector/memory cells (CD4(+) CD25(lo) ) were increased at 6 h and accompanied by
      increases in CD80(+) and CD86(+) plasmacytoid dendritic cells (pDCs). Ex vivo
      grass antigen-driven T-cell proliferative responses and the frequency of IL-4(+)
      CD4(+) T cells were significantly increased at 6 h after NAC when compared to the
      control day. CONCLUSION: Basophil, T-cell, and dendritic cell activation
      increased the frequency of allergen-driven IL-4(+) CD4(+) T cells, and T-cell
      proliferative responses are detectable in the periphery after NAC. These data
      confirm systemic cellular activation following a local nasal provocation.

PMID- 25377910
TI  - Angiotensin II-induced hypertension blunts thick ascending limb NO production by
      reducing NO synthase 3 expression and enhancing threonine 495 phosphorylation.
AB  - Thick ascending limbs reabsorb 30% of the filtered NaCl load. Nitric oxide (NO)
      produced by NO synthase 3 (NOS3) inhibits NaCl transport by this segment. In
      contrast, chronic angiotensin II (ANG II) infusion increases net thick ascending
      limb transport. NOS3 activity is regulated by changes in expression and
      phosphorylation at threonine 495 (T495) and serine 1177 (S1177), inhibitory and
      stimulatory sites, respectively. We hypothesized that NO production by thick
      ascending limbs is impaired by chronic ANG II infusion, due to reduced NOS3
      expression, increased phosphorylation of T495, and decreased phosphorylation of
      S1177. Rats were infused with 200 ng.kg(-1).min(-1) ANG II or vehicle for 1 and 5
      days. ANG II infusion for 5 days decreased NOS3 expression by 40 +/- 12% (P <
      0.007; n = 6) and increased T495 phosphorylation by 147 +/- 26% (P < 0.008; n =
      6). One-day ANG II infusion had no significant effect. NO production in response
      to endothelin-1 was blunted in thick ascending limbs from ANG II-infused animals
      [ANG II -0.01 +/- 0.06 arbitrary fluorescence units (AFU)/min vs. 0.17 +/- 0.02
      AFU/min in controls; P < 0.01]. This was not due to reduced endothelin-1 receptor
      expression. Phosphatidylinositol 3,4,5-triphosphate (PIP3)-induced NO production
      was also reduced in ANG II-infused rats (ANG II -0.07 +/- 0.06 vs. 0.13 +/- 0.04
      AFU/min in controls; P < 0.03), and this correlated with an impaired ability of
      PIP3 to increase S1177 phosphorylation. We conclude that in ANG II-induced
      hypertension NO production by thick ascending limbs is impaired due to decreased
      NOS3 expression and altered phosphorylation. 

PMID- 25377911
TI  - HMGB1 exacerbates renal tubulointerstitial fibrosis through facilitating M1
      macrophage phenotype at the early stage of obstructive injury.
AB  - Previous studies have indicated that macrophage phenotype diversity is involved
      in the progression of renal fibrosis. However, the factors facilitating M1 or M2
      phenotypes and the function of these polarized macrophages in kidney injury and
      fibrosis remain largely unknown. In the present study, we found that macrophages
      accumulated in the kidney interstitium exhibited mainly as the M1 phenotype at
      the early stage of unilateral ureter obstruction (UUO). High-mobility group box 1
      (HMGB1) protein expressed and released from tubular epithelial cells and
      interstitial macrophages was essential for the M1 macrophage transition. HMGB1
      significantly induced the expression of the M1 marker inducible nitric oxide
      synthase while decreasing the M2 marker IL-10 in macrophages. Moreover, a
      glycyrrhizic acid derivative, a blocker of HMGB1 release, reduced UUO-mediated
      kidney injury and ameliorated UUO-induced renal fibrosis. Interestingly and
      importantly, UUO caused a low pH value in the urine accumulated in the obstructed
      ureter, and the acidified urine induced HMGB1 release from tubular epithelial
      cells and macrophages in vitro. Our data demonstrate that HMGB1 is an essential
      contributor in facilitating M1 polarization at the early stage of UUO. Inhibition
      of HMGB1 release may alter macrophage phenotype and contribute to the protection
      of kidney tissue from injury and fibrosis. 

PMID- 25377912
TI  - Renal NHE expression and activity in neonatal NHE3- and NHE8-null mice.
AB  - Na(+)/H(+) exchanger (NHE)3 is the predominant NHE on the brush-border membrane
      of the proximal tubule in adult animals. NHE8 has been localized to the brush
      border membrane of proximal tubules and is more highly expressed in neonates than
      in adult animals. However, the relative role of NHE8 in neonatal renal
      acidification is unclear. The present study examined if there was a compensatory
      increase in NHE3 in NHE8-null neonatal mice and whether there was a compensatory
      increase in NHE8 in NHE3-null neonatal mice. In addition, we examined whether
      wild-type, NHE3-null, and NHE8-null mice had an increase in NHE activity in
      response to metabolic acidosis. We found that at baseline, there was comparable
      renal NHE3 mRNA, total protein, and brush-border membrane protein abundance as in
      neonatal control and NHE8-null mice. There was comparable renal NHE8 mRNA, total
      protein, and brush-border membrane protein abundance in NHE3-null neonatal and
      control mice. Both NHE3- and NHE8-null mice had a comparable but lower rate of
      NHE activity than control mice. We next imposed metabolic acidosis in wild-type,
      NHE3-null, and NHE8-null mice. Acidemic NHE8-null mice had an increase in brush
      border membrane vesicle NHE3 protein abundance and NHE activity compared with
      vehicle-treated mice. Likewise, NHE3-null mice had an increase in NHE8 brush
      border membrane protein abundance and NHE activity in response to metabolic
      acidosis. In conclusion, both NHE3 and NHE8 likely play a role in neonatal
      acidification. 

PMID- 25377914
TI  - Mesenchymal stem cells and their secretome partially restore nerve and urethral
      function in a dual muscle and nerve injury stress urinary incontinence model.
AB  - Childbirth injures muscles and nerves responsible for urinary continence.
      Mesenchymal stem cells (MSCs) or their secretome given systemically could provide
      therapeutic benefit for this complex multisite injury. We investigated whether
      MSCs or their secretome, as collected from cell culture, facilitate recovery from
      simulated childbirth injury. Age-matched female Sprague-Dawley rats received
      pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous
      (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv
      saline. Additional rats received PNC+VD and a single intraperitoneal (ip)
      injection of concentrated media conditioned by MSCs (CCM) or concentrated control
      media (CM). Controls received a sham injury and ip CM. Urethral and nerve
      function were assessed with leak point pressure (LPP) and pudendal nerve sensory
      branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal
      nerve anatomy were assessed qualitatively by blinded investigators. Quantitative
      data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P <
      0.05 indicating significant differences. Both LPP and PNSBP were significantly
      decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats,
      but not with MSC or CCM. Elastic fiber density in the urethra increased and
      changed in orientation after PNC+VD, with a greater increase in elastic fibers
      with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped
      after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide
      similar protective effects after PNC+VD, suggesting that MSCs act via their
      secretions in this dual muscle and nerve injury. 

PMID- 25377913
TI  - The discovery of hypertension: evolving views on the role of the kidneys, and
      current hot topics.
AB  - Primary hypertension is increasingly common and is associated with significant
      morbidity. Here, we review the history of its discovery and rise during the last
      century with an emphasis on studies trying to identify its cause. Early studies
      identified a defect in sodium excretion by the kidney as being central to the
      pathogenesis. Recent studies have focused on a variety of genetic, congenital
      (fetal programming), and acquired mechanisms for causing the defect in
      natriuresis. Certain risk factors are apparent, including genetic polymorphisms
      that regulate sodium excretion, a congenital reduction in nephron number, obesity
      and hyperleptinemia, an elevated sympathetic nervous system, diet (salt and
      fructose), and metabolic (hyperuricemia) mechanisms. The kidney shows evidence
      for renal arteriolar vasoconstriction, an intrarenal inflammatory response, local
      oxidative stress, and intrarenal activation of the renin-angiotensin system.
      Recent studies suggest that intrarenal T cells have an important role in causing
      hypertension to be persistent, likely due to the induction of a local autoimmune
      response to neoantigens such as heat shock protein 70 and protein aggregates
      formed by isoketals resulting from lipid peroxidation. Salt retention due to
      impairment in pressure-diuresis leads to the release of cardiotonic steroids and
      central nervous system effects that cause systemic vasoconstriction and a rise in
      blood pressure. Some recent studies suggest that salt may increase blood pressure
      not simply by effects on extracellular volume but rather as a consequence of
      hyperosmolarity. These new insights could lead to new approaches for the
      prevention and treatment of this important disease. 

PMID- 25377916
TI  - Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated
      type 1 diabetes mellitus.
AB  - Plasma uric acid (PUA) is associated with metabolic, cardiovascular, and renal
      abnormalities in patients with type 2 diabetes but is less well understood in
      type 1 diabetes (T1D). Our aim was to compare PUA levels and fractional uric acid
      excretion (FEUA) in patients with T1D vs. healthy controls (HC) during euglycemia
      and hyperglycemia. PUA, FEUA, blood pressure (BP), glomerular filtration rate
      (GFR-inulin), and effective renal plasma flow (ERPF-paraaminohippurate) were
      evaluated in patients with T1D (n = 66) during clamped euglycemia (glucose 4-6
      mmol/l) and hyperglycemia (9-11 mmol/l), and in HC (n = 41) during euglycemia. To
      separate the effects of hyperglycemia vs. increased glycosuria, parameters were
      evaluated during clamped euglycemia in a subset of T1D patients before and after
      sodium glucose cotransporter 2 (SGLT2) inhibition for 8 wk. PUA was lower in T1D
      vs. HC (228 +/- 62 vs. 305 +/- 75 MUmol/l, P < 0.0001). In T1D, hyperglycemia
      further decreased PUA (228 +/- 62 to 199 +/- 65 MUmol/l, P < 0.0001), which was
      accompanied by an increase in FEUA (7.3 +/- 3.8 to 11.6 +/- 6.7, P < 0.0001). In
      T1D, PUA levels correlated positively with SBP (P = 0.029) and negatively with
      ERPF (P = 0.031) and GFR (P = 0.028). After induction of glycosuria with SGLT2
      inhibition while maintaining clamped euglycemia, PUA decreased (P < 0.0001) and
      FEUA increased (P < 0.0001). PUA is lower in T1D vs. HC and positively correlates
      with SBP and negatively with GFR and ERPF in T1D. Glycosuria rather than
      hyperglycemia increases uricosuria in T1D. Future studies examining the effect of
      uric acid-lowering therapies should account for the impact of ambient glycemia,
      which causes an important uricosuric effect. 

PMID- 25377915
TI  - Pharmacological inhibition of soluble epoxide hydrolase prevents renal
      interstitial fibrogenesis in obstructive nephropathy.
AB  - Treating chronic kidney disease (CKD) has been challenging because of its
      pathogenic complexity. Epoxyeicosatrienoic acids (EETs) are cytochrome P-450
      dependent derivatives of arachidonic acid with antihypertensive, anti
      inflammatory, and profibrinolytic functions. We recently reported that genetic
      ablation of soluble epoxide hydrolase (sEH), an enzyme that converts EETs to less
      active dihydroxyeicosatrienoic acids, prevents renal tubulointerstitial fibrosis
      and inflammation in experimental mouse models of CKD. Here, we tested the
      hypothesis that pharmacological inhibition of sEH after unilateral ureteral
      obstruction (UUO) would attenuate tubulointerstitial fibrosis and inflammation in
      mouse kidneys and may provide a novel approach to manage the progression of CKD.
      Inhibition of sEH enhanced levels of EET regioisomers and abolished
      tubulointerstitial fibrosis, as demonstrated by reduced collagen deposition and
      myofibroblast formation after UUO. The inflammatory response was also attenuated,
      as demonstrated by decreased influx of neutrophils and macrophages and decreased
      expression of inflammatory cytokines keratinocyte chemoattractant, macrophage
      inflammatory protein-2, monocyte chemotactic protein-1, TNF-alpha, and ICAM-1 in
      kidneys after UUO. UUO upregulated transforming growth factor-beta1/Smad3
      signaling and induced NF-kappaB activation, oxidative stress, tubular injury, and
      apoptosis; in contrast, it downregulated antifibrotic factors, including
      peroxisome proliferator-activated receptor (PPAR) isoforms, especially PPAR
      gamma. sEH inhibition mitigated the aforementioned malevolent effects in UUO
      kidneys. These data demonstrate that pharmacological inhibition of sEH promotes
      anti-inflammatory and fibroprotective effects in UUO kidneys by preventing
      tubular injury, downregulation of NF-kappaB, transforming growth factor
      beta1/Smad3, and inflammatory signaling pathways, and activation of PPAR
      isoforms. Our data suggest the potential use of sEH inhibitors in treating
      fibrogenesis in the UUO model of CKD. 

PMID- 25377917
TI  - The chronic hypoxia hypothesis: the search for the smoking gun goes on.

PMID- 25377918
TI  - Vasopressin regulation of multisite phosphorylation of UT-A1 in the inner
      medullary collecting duct.
AB  - Vasopressin signaling is critical for the regulation of urea transport in the
      inner medullary collecting duct (IMCD). Increased urea permeability is driven by
      a vasopressin-mediated elevation of cAMP that results in the direct
      phosphorylation of urea transporter (UT)-A1. The identification of cAMP-sensitive
      phosphorylation sites, Ser(486) and Ser(499), in the rat UT-A1 sequence was the
      first step in understanding the mechanism of vasopressin action on the
      phosphorylation-dependent modulation of urea transport. To investigate the
      significance of multisite phosphorylation of UT-A1 in response to elevated cAMP,
      we used highly specific and sensitive phosphosite antibodies to Ser(486) and
      Ser(499) to determine cAMP action at each phosphorylation site. We found that
      phosphorylation at both sites was rapid and sustained. Furthermore, the rate of
      phosphorylation of the two sites was similar in both mIMCD3 cells and rat inner
      medullary tissue. UT-A1 localized to the apical membrane in response to
      vasopressin was phosphorylated at Ser(486) and Ser(499). We confirmed that
      elevated cAMP resulted in increased phosphorylation of both sites by PKA but not
      through the vasopressin-sensitive exchange protein activated by cAMP pathway.
      These results elucidate the multisite phosphorylation of UT-A1 in response to
      cAMP, thus providing the beginning of understanding the intracellular factors
      underlying vasopressin stimulation of urea transport in the IMCD. 

PMID- 25377919
TI  - Application of a novel regulatable Cre recombinase system to define the role of
      liver and gut metabolism in drug oral bioavailability.
AB  - The relative contribution of hepatic compared with intestinal oxidative
      metabolism is a crucial factor in drug oral bioavailability and therapeutic
      efficacy. Oxidative metabolism is mediated by the cytochrome P450 mono-oxygenase
      system to which cytochrome P450 reductase (POR) is the essential electron donor.
      In order to study the relative importance of these pathways in drug disposition,
      we have generated a novel mouse line where Cre recombinase is driven off the
      endogenous Cyp1a1 gene promoter; this line was then crossed on to a floxed POR
      mouse. A 40 mg/kg dose of the Cyp1a1 inducer 3-methylcholanthrene (3MC)
      eliminated POR expression in both liver and small intestine, whereas treatment at
      4 mg/kg led to a more targeted deletion in the liver. Using this approach, we
      have studied the pharmacokinetics of three probe drugs--paroxetine, midazolam,
      nelfinavir--and show that intestinal metabolism is a determinant of oral
      bioavailability for the two latter compounds. The Endogenous Reductase Locus
      (ERL) mouse represents a significant advance on previous POR deletion models as
      it allows direct comparison of hepatic and intestinal effects on drug and
      xenobiotic clearance using lower doses of a single Cre inducing agent, and in
      addition minimizes any cytotoxic effects, which may compromise interpretation of
      the experimental data.

PMID- 25377920
TI  - The life of phi: the development of phi thickenings in roots of the orchids of
      the genus Miltoniopsis.
AB  - Phi thickenings, bands of secondary wall thickenings that reinforce the primary
      wall of root cortical cells in a wide range of species, are described for the
      first time in the epiphytic orchid Miltoniopsis. As with phi thickenings found in
      other plants, the phi thickenings in Miltoniopsis contain highly aligned
      cellulose running along the lengths of the thickenings, and are lignified but not
      suberized. Using a combination of histological and immunocytochemical techniques,
      thickening development can be categorized into three different stages.
      Microtubules align lengthwise along the thickening during early and intermediate
      stages of development, and callose is deposited within the thickening in a
      pattern similar to the microtubules. These developing thickenings also label with
      the fluorescently tagged lectin wheat germ agglutinin (WGA). These associations
      with microtubules and callose, and the WGA labeling, all disappear when the phi
      thickenings are mature. This pattern of callose and WGA deposition show changes
      in the thickened cell wall composition and may shed light on the function of phi
      thickenings in plant roots, a role for which has yet to be established. 

PMID- 25377921
TI  - Does the extracorporeal blood flow affect survival of the arteriovenous vascular
      access?
AB  - Hemodiafiltration with high-convective volumes is associated with improved
      patient survival, whereby practical realization is contingent on high
      extracorporeal blood flow (Qb) and dialysis treatment time. However, Qb is
      restricted by vascular access (VA) quality and/or concerns that high Qb could
      damage the VA. Taking VA quality into consideration, one can investigate the
      relationship between Qb and VA survival. We analyzed data from 1039 patients
      treated by hemodiafiltration over a 21-month period where access blood flow (Qa)
      measurements were also available at baseline. VA failure was defined as a
      surgical intervention resulting in the generation of a new VA. Qa was included as
      a stratification variable within a Cox regression model. A second Cox
      proportional hazard model with a penalized spline was used to describe the
      association between Qb and VA survival. Compared with Qb in the 350-357 mL/min
      range, a significantly higher hazard ratio (HR) for VA failure was detected for
      fistula only, and then only for Qb < 312 mL/min (HR: 2.361, 95% confidence
      interval [CI]: 1.251-4.453), Qb = 387-397 mL/min (HR: 1.920, 95% CI: 1.007-3.660)
      and Qb >414 mL/min (HR: 2.207, 95% CI: 1.101-4.424). Age, gender, diabetes, VA
      vintage, position of the VA, and arterial pressure were not significantly
      associated with outcome. The form of the penalized spline confirmed higher risk
      for VA failure for the lowest and the highest values of Qb. Taking Qa into
      consideration, no association was found between VA failure and Qb up to flows as
      high as approximately 390 mL/min. 

PMID- 25377922
TI  - Stereoselective synthesis of alpha-linked 2-deoxy glycosides enabled by visible
      light-mediated reductive deiodination.
AB  - 2-Deoxy sugars and their derivatives occur abundantly in many pharmaceutically
      important natural products. However, the construction of specific 2-deoxy
      glycosidic bonds remains as a challenge. Herein, we report an efficient way to
      prepare 2-deoxy-alpha-glycosides by glycosylation of 2-iodo-glycosyl acetate and
      subsequent visible-light-mediated tin-free reductive deiodination. We have
      successfully applied the postglycosylational-deiodination strategy in the
      synthesis of more than 30 mono-, di-, tri-, tetra- and pentadeoxysaccharides with
      excellent stereoselectivity and efficiency. This method has also been applied to
      the synthesis of a 2-deoxy-tetrasaccharide containing four alpha-linkages. 

PMID- 25377923
TI  - Determination of apoptosis in actinic prurigo by TUNEL technique.

PMID- 25377924
TI  - Towards a high thermoelectric performance in rare-earth substituted SrTiO3:
      effects provided by strongly-reducing sintering conditions.
AB  - Donor-substituted strontium titanate ceramics demonstrate one of the most
      promising performances among n-type oxide thermoelectrics. Here we report a
      marked improvement of the thermoelectric properties in rare-earth substituted
      titanates Sr0.9R0.1TiO3+/-delta (R = La, Ce, Pr, Nd, Sm, Gd, Dy, Y) to achieve
      maximal ZT values of as high as 0.42 at 1190 K < T < 1225 K, prepared via a
      conventional solid state route followed by sintering under strongly reducing
      conditions (10%H2-90%N2, 1773 K). As a result of complex defect chemistry, both
      electrical and thermal properties were found to be dependent on the nature of the
      rare-earth cation and exhibit an apparent correlation with the unit cell size.
      High power factors of 1350-1550 MUW m(-1) K(-2) at 400-550 K were observed for R
      = Nd, Sm, Pr and Y, being among the largest reported so far for n-type conducting
      bulk-ceramic SrTiO3-based materials. Attractive ZT values at high temperatures
      arise primarily from low thermal conductivity, which, in turn, stem from
      effective phonon scattering in oxygen-deficient perovskite layers formed upon
      reduction. The results suggest that highly-reducing conditions are essential and
      should be employed, whenever possible, in other related micro/nanostructural
      engineering approaches to suppress the thermal conductivity in target titanate
      based ceramics. 

PMID- 25377926
TI  - A meta-analysis of the diagnostic accuracy of Autism Diagnostic Observation
      Schedule Module-1 for autism spectrum disorders.
AB  - OBJECTIVE: Autism Diagnostic Observation Schedule (ADOS) is considered gold
      standard for the diagnosis of Autism Spectrum Disorders (ASD). The authors
      evaluated the cumulative diagnostic accuracy of ADOS-Module 1 (ADOS(M1)) using
      the original diagnostic algorithm with meta-analysis and meta-regression.
      METHODS: The authors, electronically and manually searched for studies from 1999
      to 2013 that evaluated the accuracy of ADOS(M1) using the original diagnostic
      algorithm in detecting ASD. Primary results of Sensitivity (Sn), Specificity (Sp)
      and Diagnostic Odds Ratio (DOR) for ADOS(M1) were summarized using random-effects
      model. Summary Receiver Operating characteristic Curves and its Area Under the
      Curve (SROC-AUC) were used to summarize overall diagnostic accuracy of ADOS(M1).
      The modifying effects of quality of study and sample size, on the diagnostic odds
      ratio, were investigated using meta-regression. RESULTS: A total of 7 cross
      sectional studies provided data on 4057 children. The pooled Sn, Sp, DOR and SROC
      AUC for the overall diagnostic accuracy of ADOS (M1) were: 0.91 (95 %CI=0.89 to
      0.93), 0.73 (95 % CI=0.69 to 0.76), 44.20 (95 %CI=15.89 to 122.95) and 0.90
      respectively [corrected]. Meta-regression analysis showed a non-significant
      relationship between ADOS(M1) and study quality as well as sample size. There
      were subgroup differences in the DOR. CONCLUSIONS: It is concluded that ADOS (M1)
      with the original diagnostic algorithm has the overall diagnostic accuracy and
      pooled specificity suggesting moderate accuracy. The pooled sensitivity is high
      to be used as a screening test for Autism Spectrum Disorders. ADOS( M1)with the
      revised diagnostic algorithm should be used for diagnostic purpose [corrected]
      ADOS(M1) with the revised diagnostic algorithm should be used instead for the
      diagnosis of this group of disorders.

PMID- 25377925
TI  - GYY4137, a hydrogen sulfide-releasing molecule, inhibits the inflammatory
      response by suppressing the activation of nuclear factor-kappa B and mitogen
      activated protein kinases in Coxsackie virus B3-infected rat cardiomyocytes.
AB  - GYY4137 is a water-soluble, small molecule hydrogen sulfide (H2S)-release agent
      that possesses potent cardioprotective and anti-inflammatory properties in
      experimental models. Coxsackie virus B3 (CVB3) infection commonly causes viral
      myocarditis, which mainly involves immune cell infiltration, eventually resulting
      in heart failure. In the present study, the effects and underlying mechanisms of
      GYY4137 treatment of CVB3-induced myocarditis were investigated. The effects of
      GYY4137 on CVB3-induced nuclear factor-kappa B (NF-kappaB) activity were examined
      by western blotting, immunofluorescence and electrophoretic mobility shift assay.
      Mitogen-activated protein kinase (MAPK) signaling protein expression levels were
      detected by western blotting. Cardiomyocyte damage-related enzyme activities,
      such as lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB), were measured
      by ELISA, as well as the production of proinflammatory cytokines. The results
      revealed that GYY4137 suppressed CVB3-induced secretion of LDH, CK-MB and pro
      inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin (IL)
      1beta and IL-6. Furthermore, the activation of NF-kappaB and the IkappaBalpha
      degradation induced by CVB3 were also inhibited by GYY4137. Notably, the
      phosphorylation of p38, ERK1/2 and JNK1/2 induced by CVB3 was also inhibited by
      GYY4137. In conclusion, the data demonstrate that GYY4137 exerts anti
      inflammatory effects in CVB3-infected cardiomyocytes. This anti-inflammatory
      mechanism may be associated with suppression of NF-kappaB and MAPK signaling
      pathway activation.

PMID- 25377927
TI  - The effects of bruising and temperature on enzyme activity and textural qualities
      of tomato juice.
AB  - BACKGROUND: During harvest and transportation, processing tomatoes are exposed to
      elevated temperatures, compression and vibration in the harvester and truck,
      making them prone to bruising. The objective of this study was to determine how
      bruising and exposure to high temperatures affect pectin methylesterase (PME)
      activation and the textural quality of tomato juice. RESULTS: Tomatoes were both
      hand and mechanically harvested using current harvest practices. Mechanically
      harvested fruits were significantly softer, had greater PME activity and greater
      juice consistency than hand harvested fruits. In a controlled bruising study,
      whole tomatoes were exposed to various compressive forces at 21 or 40  degrees C
      and held for 0 or 4 h. Greater bruising force and higher temperature resulted in
      a decrease in firmness and an increase in PME activity. Consistency of tomato
      juice improved when tomatoes were exposed to 40  degrees C. Tomatoes subjected to
      a temperature range from 21 to 65  degrees C had activated PME at 40  degrees C
      and increased activity as temperature increased. Consistency increased at 35 
      degrees C but decreased with increasing temperature. CONCLUSION: Tomatoes
      harvested using current mechanical techniques are likely to be less firm and have
      increased PME activity; however, increased consistency of processed juice is
      observed. Tomatoes harvested at higher temperatures are also likely to have
      better consistency when processed.

PMID- 25377929
TI  - Child's Weight Status and Parent's Response to a School-Based Body Mass Index
      Screening and Parent Notification Program.
AB  - This study examined the response of parents of elementary school-aged children to
      a school-based body mass index (BMI) screening and parent notification program
      conducted in one Minnesota school district in 2010-2011 and whether parent's
      response was moderated by child's weight status. Randomly selected parents (N =
      122) of second- and fourth-grade students completed a mailed self-administered
      anonymous survey. Child's weight status was determined using measured height and
      weight. Most parents read the BMI notification letter and considered it helpful,
      independent of child's weight status. Parents of overweight children were
      significantly more likely than parents of normal weight children to report
      healthy lifestyle changes. This low-intensity intervention has the potential to
      support children, especially overweight children, and their parents to make
      healthy lifestyle changes. Future studies should investigate whether parent's
      response contributes to improved short- and long-term health outcomes for
      children. 

PMID- 25377930
TI  - Differences in Access to Care Among Students Using School-Based Health Centers.
AB  - Health care reform has changed the landscape for the nation's health safety net,
      and school-based health centers (SBHCs) remain an important part of this system.
      However, few large-scale studies have been conducted to assess their impact on
      access to care. This study investigated differences in access among a nationally
      representative sample of adolescent SBHC users. An analysis using multivariate
      logistic regression examined the association between student characteristics and
      access to care. We found no differences based on race/ethnicity or insurance
      status among adolescent SBHC users; however, we did observe significant
      differences with regard to unmet health needs. School nurses serve as invaluable
      frontline staff who can facilitate equitable access to care, provide high-quality
      primary care, coordinate care for students with community health services, and
      advocate for policy and funding support of SBHCs as a critical part of the safety
      net for underserved adolescents. 

PMID- 25377928
TI  - Loss to follow-up in the Australian HIV Observational Database.
AB  - BACKGROUND: Loss to follow-up (LTFU) in HIV-positive cohorts is an important
      surrogate for interrupted clinical care, which can potentially influence the
      assessment of HIV disease status and outcomes. After preliminary evaluation of
      LTFU rates and patient characteristics, we evaluated the risk of mortality by
      LTFU status in a high-resource setting. METHODS: Rates of LTFU were measured in
      the Australian HIV Observational Database for a range of patient characteristics.
      Multivariate repeated measures regression methods were used to identify
      determinants of LTFU. Mortality by LTFU status was ascertained using linkage to
      the National Death Index. Survival following combination antiretroviral therapy
      initiation was investigated using the Kaplan-Meier (KM) method and Cox
      proportional hazards models. RESULTS: Of 3,413 patients included in this
      analysis, 1,632 (47.8%) had at least one episode of LTFU after enrolment.
      Multivariate predictors of LTFU included viral load (VL)>10,000 copies/ml (rate
      ratio [RR] 1.63; 95% CI 1.45, 1.84; ref <=400), time under follow-up (per year;
      RR 1.03; 95% CI 1.02, 1.04) and prior LTFU (per episode; RR 1.15; 95% CI 1.06,
      1.24). KM curves for survival were similar by LTFU status (P=0.484). LTFU was not
      associated with mortality in Cox proportional hazards models (univariate hazard
      ratio [HR] 0.93; 95% CI 0.69, 1.26) and multivariate HR 1.04 (95% CI 0.77, 1.43).
      CONCLUSIONS: Increased risk of LTFU was identified amongst patients with
      potentially higher infectiousness. We did not find significant mortality risk
      associated with LTFU. This is consistent with timely re-engagement with
      treatment, possibly via high levels of unreported linkage to other health-care
      providers.

PMID- 25377931
TI  - Time Spent on the Internet and Adolescent Blood Pressure.
AB  - Internet use is nearly ubiquitous among adolescents. Growing evidence suggests
      heavy Internet use negatively impacts health, yet the relationship between time
      spent on the Internet and adolescent blood pressure (BP) is unknown. We examined
      the association between Internet use and elevated BP in a racially diverse cross
      sectional sample of 331 healthy adolescents (ages 14-17 years). Heavy Internet
      use was defined as >= 2 hr/day, moderate use as <2 hr/day and >= 5 days/week, and
      light use as < 2 hr/day and <= 4 days/week. Elevated BP was defined as systolic
      or diastolic BP >= 90 th percentile. Heavy Internet users had statistically
      significantly higher odds of elevated BP compared to light Internet users. School
      nurses can play an important role in preventing high BP through assessment of BP
      and other health behaviors including Internet use, and health teaching to
      individuals, student groups, faculty, and parents to increase awareness of the
      relationship between Internet use and health.

PMID- 25377932
TI  - Senescence, ageing and death of the whole plant: morphological prerequisites and
      constraints of plant immortality.

PMID- 25377933
TI  - Characterizing the PK/PD relationship for inhibition of capsaicin-induced dermal
      vasodilatation by MK-3207, an oral calcitonin gene related peptide receptor
      antagonist.
AB  - AIMS: Calcitonin gene related peptide (CGRP) receptor antagonists are effective
      acute migraine treatments. A capsaicin-induced dermal vasodilatation (CIDV) model
      has been developed to provide target-engagement information in healthy
      volunteers. In the model, CGRP release is provoked after dermal capsaicin
      application, by activating transient receptor potential vanilloid-type-1 (TRPV1)
      receptors at peripheral sensory nerves. Laser Doppler imaging is used to quantify
      CIDV and subsequent inhibition by CGRP receptor antagonists. We sought to
      evaluate a CGRP receptor antagonist, MK-3207, in the biomarker model and to
      assess the predictability of the CIDV response to migraine clinical efficacy.
      METHODS: An integrated population pharmacokinetic/pharmacodynamic (PK/PD) model
      was developed to describe the exposure-response relationship for CIDV inhibition
      by CGRP and TRPV1 receptor antagonists. MK-3207 dose-response predictions were
      made based on estimated potency from the PK/PD model and mean plasma
      concentrations observed at the doses investigated. RESULTS: The results suggested
      that a 20 mg dose of MK-3207 (EC50 of 1.59 nm) would be required to attain the
      peripheral CIDV response at a target level that was shown previously to correlate
      with 2 h clinical efficacy based on phase 3 telcagepant clinical data, and that a
      plateau of the dose-response would be reached around 40-100 mg. These predictions
      provided a quantitative rationale for dose selection in a phase 2 clinical trial
      of MK-3207 and helped with interpretation of the efficacy results from the trial.
      CONCLUSIONS: The integrated CIDV PK/PD model provides a useful platform for
      characterization of PK/PD relationships and predictions of dose-response
      relationships to aid in future development of CGRP and TRPV1 receptor
      antagonists.

PMID- 25377934
TI  - Video modelling for reducing anxiety related to the use of nasal masks place it
      for inhalation sedation: a randomised clinical trial.
AB  - AIM: A randomised controlled trial to investigate if video modelling can reduce
      the level of dental anxiety and increase the patient's acceptance of the nasal
      mask usage for children receiving dental treatment using inhalation sedation
      (IS). METHODS: A sample of 80 (8-16 years) children due to have dental treatments
      under IS were randomly allocated to either the modelling video or the control
      video (oral hygiene instruction). The level of anxiety was recorded before and
      after watching the video on the Abeer Children Dental Anxiety Scale and each
      child's ability to cope with the subsequent procedure was assessed on the visual
      analogue scale. A two-group Chi-square test was used as the basis for the sample
      size calculation; a significance level of 0.025 was chosen rather than the
      conventional 0.05 to avoid spurious results arising from multiple testing.
      RESULTS: Children in the test group had significantly less anxiety after watching
      the video than those in the control group throughout the subsequent dental
      procedure; particullary, at the time of the nasal mask administration (P<0.001).
      CONCLUSIONS: Video modelling appeared to be effective at reducing dental anxiety
      and has a significant impact on the acceptance of the nasal mask administration
      for Inhalation Sedation in children.

PMID- 25377935
TI  - Significant association between human osteosarcoma and simian virus 40.
AB  - BACKGROUND: Simian virus 40 (SV40) has been considered to be an oncogenic viral
      agent in the development of osteosarcoma (OS), which to the authors' knowledge
      continues to be of unknown etiology. METHODS: In the current study, serum samples
      from patients with OS were investigated with an indirect enzyme-linked
      immunoadsorbent assay (ELISA) to test for the presence of immunoglobulin G
      antibodies, which react with SV40 antigens. In ELISA, SV40 antigens were
      represented by 2 synthetic polypeptides that mimic epitopes of the viral capsid
      proteins 1 to 3. Additional sera from patients with breast cancer and
      undifferentiated nasopharyngeal carcinoma as well as healthy subjects were the
      controls. RESULTS: Immunologic results suggested that antibodies that react with
      SV40 mimotopes were more prevalent (44%) in serum samples from patients with OS
      compared with healthy subjects (17%). The difference in prevalence between these
      cohorts was statistically significant (P<.001). It is interesting to note that in
      the patients with OS, significance indicated the difference between OS versus
      breast cancer (44% vs 15%; P<.001) and OS versus undifferentiated nasopharyngeal
      carcinoma (44% vs 25%; P<.05). CONCLUSIONS: The data from the current study
      indicate an association between OS and SV40. These data could be transferred to
      clinical applications for innovative therapies to address SV40-positive OS.

PMID- 25377936
TI  - Topographical extracellular matrix cues on anticancer drug-induced cytotoxicity
      in stem cells.
AB  - In recent years, cell chip-based platforms have begun to show promise as a means
      of corroborating the findings of in vivo animal tests for cytotoxicity, and
      perhaps in the future partially replacing the need for such animal models. In
      contrast to the conventional culture methods, micro- and nanofabrication
      techniques can be utilized to provide a set of mechanostimulatory signals to the
      cells that mimic the context of extracellular matrix (ECM) of the tissue in which
      a particular cell line resides. Here, we report periodic lateral topographic
      striations, with a pitch ranging approximately from 200 to 800 nm with an
      intention to mimic a common geometry of fibrils in the ECM such as collagen or
      elastin, as a platform for investigating anticancer drug-induced cytotoxicity in
      stem cells. The ECM cues could facilitate perimeter, elongation, and gap junction
      formation of mesenchymal stem cells (MSCs), which eventually influenced the fate
      of cells in terms of death and survival against the common chemotherapeutic agent
      cisplatin. Interestingly, the appropriate inhibition of gap junctions of MSCs on
      the ECM mimicking substrates could prevent the cisplatin-induced cytotoxicity
      through the inhibition of the cisplatin-induced 'death signal communication' as
      compared to that on the flat substrates. Our results imply that nanoscale
      topography is an important consideration for chip-based cytotoxicity assays,
      which uniquely enable the consideration and rational design of ECM-like
      topographic features, and furthermore, that the natural topography of the ECM in
      the context of stem cell niches may serve as an important indicator for
      chemotherapeutic agent sensitivity.

PMID- 25377937
TI  - Applicability of the polynomial chaos expansion method for personalization of a
      cardiovascular pulse wave propagation model.
AB  - Patient-specific modeling requires model personalization, which can be achieved
      in an efficient manner by parameter fixing and parameter prioritization. An
      efficient variance-based method is using generalized polynomial chaos expansion
      (gPCE), but it has not been applied in the context of model personalization, nor
      has it ever been compared with standard variance-based methods for models with
      many parameters. In this work, we apply the gPCE method to a previously reported
      pulse wave propagation model and compare the conclusions for model
      personalization with that of a reference analysis performed with Saltelli's
      efficient Monte Carlo method. We furthermore differentiate two approaches for
      obtaining the expansion coefficients: one based on spectral projection (gPCE-P)
      and one based on least squares regression (gPCE-R). It was found that in general
      the gPCE yields similar conclusions as the reference analysis but at much lower
      cost, as long as the polynomial metamodel does not contain unnecessary high order
      terms. Furthermore, the gPCE-R approach generally yielded better results than
      gPCE-P. The weak performance of the gPCE-P can be attributed to the assessment of
      the expansion coefficients using the Smolyak algorithm, which might be hampered
      by the high number of model parameters and/or by possible non-smoothness in the
      output space.

PMID- 25377939
TI  - Domestication of the dog from the wolf was promoted by enhanced excitatory
      synaptic plasticity: a hypothesis.
AB  - Dogs shared a much closer relationship with humans than any other domesticated
      animals, probably due to their unique social cognitive capabilities, which were
      hypothesized to be a by-product of selection for tameness toward humans. Here, we
      demonstrate that genes involved in glutamate metabolism, which account partially
      for fear response, indeed show the greatest population differentiation by whole
      genome comparison of dogs and wolves. However, the changing direction of their
      expression supports a role in increasing excitatory synaptic plasticity in dogs
      rather than reducing fear response. Because synaptic plasticity are widely
      believed to be cellular correlates of learning and memory, this change may alter
      the learning and memory abilities of ancient scavenging wolves, weaken the fear
      reaction toward humans, and prompt the initial interspecific contact. 

PMID- 25377940
TI  - Multispecies coalescent analysis of the early diversification of neotropical
      primates: phylogenetic inference under strong gene trees/species tree conflict.
AB  - Neotropical primates (NP) are presently distributed in the New World from Mexico
      to northern Argentina, comprising three large families, Cebidae, Atelidae, and
      Pitheciidae, consequently to their diversification following their separation
      from Old World anthropoids near the Eocene/Oligocene boundary, some 40 Ma. The
      evolution of NP has been intensively investigated in the last decade by studies
      focusing on their phylogeny and timescale. However, despite major efforts, the
      phylogenetic relationship between these three major clades and the age of their
      last common ancestor are still controversial because these inferences were based
      on limited numbers of loci and dating analyses that did not consider the
      evolutionary variation associated with the distribution of gene trees within the
      proposed phylogenies. We show, by multispecies coalescent analyses of selected
      genome segments, spanning along 92,496,904 bp that the early diversification of
      extant NP was marked by a 2-fold increase of their effective population size and
      that Atelids and Cebids are more closely related respective to Pitheciids. The
      molecular phylogeny of NP has been difficult to solve because of population-level
      phenomena at the early evolution of the lineage. The association of evolutionary
      variation with the distribution of gene trees within proposed phylogenies is
      crucial for distinguishing the mean genetic divergence between species (the mean
      coalescent time between loci) from speciation time. This approach, based on
      extensive genomic data provided by new generation DNA sequencing, provides more
      accurate reconstructions of phylogenies and timescales for all organisms. 

PMID- 25377943
TI  - Structurally Controlled Bio-hybrid Materials Based on Unidirectional Association
      of Anisotropic Microparticles with Human Endothelial Cells.
AB  - Biocompatible anisotropic polymer particles with bipolar affinity towards human
      endothelial cells are a novel type of building blocks for microstructured bio
      hybrid materials. Functional polarity due to two biologically distinct
      hemispheres has been achieved by synthesis of anisotropic particles via electro
      hydrodynamic co-jetting of two different polymer solutions and subsequent
      selective surface modification. 

PMID- 25377941
TI  - The genome of a Mongolian individual reveals the genetic imprints of Mongolians
      on modern human populations.
AB  - Mongolians have played a significant role in modern human evolution, especially
      after the rise of Genghis Khan (1162[?]-1227). Although the social cultural
      impacts of Genghis Khan and the Mongolian population have been well documented,
      explorations of their genome structure and genetic imprints on other human
      populations have been lacking. We here present the genome of a Mongolian male
      individual. The genome was de novo assembled using a total of 130.8-fold genomic
      data produced from massively parallel whole-genome sequencing. We identified high
      confidence variation sets, including 3.7 million single nucleotide polymorphisms
      (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis
      predicted that the individual has a pathogenic risk for carnitine deficiency. We
      located the patrilineal inheritance of the Mongolian genome to the lineage D3a
      through Y haplogroup analysis and inferred that the individual has a common
      patrilineal ancestor with Tibeto-Burman populations and is likely to be the
      progeny of the earliest settlers in East Asia. We finally investigated the
      genetic imprints of Mongolians on other human populations using different
      approaches. We found varying degrees of gene flows between Mongolians and
      populations living in Europe, South/Central Asia, and the Indian subcontinent.
      The analyses demonstrate that the genetic impacts of Mongolians likely resulted
      from the expansion of the Mongolian Empire in the 13th century. The genome will
      be of great help in further explorations of modern human evolution and genetic
      causes of diseases/traits specific to Mongolians. 

PMID- 25377942
TI  - Genome-wide patterns of polymorphism in an inbred line of the African malaria
      mosquito Anopheles gambiae.
AB  - Anopheles gambiae is a major mosquito vector of malaria in Africa. Although
      increased use of insecticide-based vector control tools has decreased malaria
      transmission, elimination is likely to require novel genetic control strategies.
      It can be argued that the absence of an A. gambiae inbred line has slowed
      progress toward genetic vector control. In order to empower genetic studies and
      enable precise and reproducible experimentation, we set out to create an inbred
      line of this species. We found that amenability to inbreeding varied between
      populations of A. gambiae. After full-sib inbreeding for ten generations, we
      genotyped 112 individuals--56 saved prior to inbreeding and 56 collected after
      inbreeding--at a genome-wide panel of single nucleotide polymorphisms (SNPs).
      Although inbreeding dramatically reduced diversity across much of the genome, we
      discovered numerous, discrete genomic blocks that maintained high heterozygosity.
      For one large genomic region, we were able to definitively show that high
      diversity is due to the persistent polymorphism of a chromosomal inversion.
      Inbred lines in other eukaryotes often exhibit a qualitatively similar retention
      of polymorphism when typed at a small number of markers. Our whole-genome SNP
      data provide the first strong, empirical evidence supporting associative
      overdominance as the mechanism maintaining higher than expected diversity in
      inbred lines. Although creation of A. gambiae lines devoid of nearly all
      polymorphism may not be feasible, our results provide critical insights into how
      more fully isogenic lines can be created.

PMID- 25377944
TI  - A proposal for a primary screening tool: 'Keep your waist circumference to less
      than half your height'.
AB  - BACKGROUND: There is now overwhelming scientific evidence that central obesity,
      as opposed to total obesity assessed by body mass index (BMI), is associated with
      the most health risks and that the waist-to-height ratio (WHtR) is a simple proxy
      for this central fat distribution. This Opinion reviews the evidence for the use
      of WHtR to predict mortality and for its association with morbidity. A boundary
      value of WHtR of 0.5 has been proposed and become widely used. This translates
      into the simple screening message 'Keep your waist to less than half your
      height'. Not only does this message appear to be suitable for all ethnic groups,
      it also works well with children. DISCUSSION: Ignoring this simple message and
      continuing to use BMI as a sole indicator of risk would mean that 10% of the
      whole UK population, and more than 25% of the UK population who are judged to be
      normal weight using BMI, are misclassified and might not be alerted to the need
      to take care or to take action. SUMMARY: Accepting that a boundary value whereby
      WHtR should be less than 0.5 not only lends itself to the simple message 'Keep
      your waist to less than half your height' but it also provides a very cheap
      primary screening method for increased health risks: A piece of string, measuring
      exactly half a person's height should fit around that person's waist.

PMID- 25377945
TI  - Planar heterojunction perovskite solar cells with superior reproducibility.
AB  - Perovskite solar cells (PeSCs) have been considered one of the competitive next
      generation power sources. To date, light-to-electric conversion efficiencies have
      rapidly increased to over 10%, and further improvements are expected. However,
      the poor device reproducibility of PeSCs ascribed to their inhomogeneously
      covered film morphology has hindered their practical application. Here, we
      demonstrate high-performance PeSCs with superior reproducibility by introducing
      small amounts of N-cyclohexyl-2-pyrrolidone (CHP) as a morphology controller into
      N,N-dimethylformamide (DMF). As a result, highly homogeneous film morphology,
      similar to that achieved by vacuum-deposition methods, as well as a high PCE of
      10% and an extremely small performance deviation within 0.14% were achieved. This
      study represents a method for realizing efficient and reproducible planar
      heterojunction (PHJ) PeSCs through morphology control, taking a major step
      forward in the low-cost and rapid production of PeSCs by solving one of the
      biggest problems of PHJ perovskite photovoltaic technology through a facile
      method. 

PMID- 25377947
TI  - Longitudinal assessments of erythropoietin-stimulating agent responsiveness and
      the association with specific clinical outcomes in dialysis patients.
AB  - BACKGROUND: Dose requirements of erythropoietin-stimulating agents (ESAs) can
      vary considerably over time and may be associated with cardiovascular outcomes.
      We aimed to longitudinally assess ESA responsiveness over time and to investigate
      its association with specific clinical end points in a time-dependent approach.
      METHODS: The German Diabetes and Dialysis study (4D study) included 1,255
      diabetic dialysis patients, of whom 1,161 were receiving ESA treatment. In those
      patients, the erythropoietin resistance index (ERI) was assessed every 6 months
      during a median follow-up of 4 years. The association between the ERI and
      cardiovascular end points was analyzed by time-dependent Cox regression analyses
      with repeated ERI measures. RESULTS: Patients had a mean age of 66 +/- 8.2 years;
      53% were male. During follow-up, a total of 495 patients died, of whom 136 died
      of sudden death and 102 of infectious death. The adjusted and time-dependent risk
      for sudden death was increased by 19% per 5-unit increase in the ERI (hazard
      ratio, HR = 1.19, 95% confidence interval, CI = 1.07-1.33). Similarly, mortality
      increased by 25% (HR = 1.25, 95% CI = 1.18-1.32) and infectious death increased
      by 27% (HR = 1.27, 95% CI = 1.13-1.42). Further analysis revealed that lower 25
      hydroxyvitamin D levels were associated with lower ESA responsiveness (p =
      0.046). CONCLUSIONS: In diabetic dialysis patients, we observed that time-varying
      erythropoietin resistance is associated with sudden death, infectious
      complications and all-cause mortality. Low 25-hydroxyvitamin D levels may
      contribute to a lower ESA responsiveness.

PMID- 25377946
TI  - Effects of pamidronate disodium on the loss of osteoarthritic subchondral bone
      and the expression of cartilaginous and subchondral osteoprotegerin and RANKL in
      rabbits.
AB  - BACKGROUND: Osteoarthritis (OA) is a major health problem in the increasingly
      elderly population. Therefore, it is crucial to prevent and treat OA at an early
      stage. The present study investigated whether pamidronate disodium (PAM), a bone
      loss inhibitor, can significantly prevent or reverse the progression of early
      anterior cruciate ligament transection (ACLT)-induced OA. Whether therapeutic
      intervention is associated with regulation of the expression of osteoprotegerin
      (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL),
      metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or
      subchondral bone was also investigated. METHODS: 60 New Zealand rabbits were
      randomized into four groups: Sham-operated (n = 20); ACLT (n = 20); short-term
      treatment with PAM (PAM-S, n = 10) and long-term treatment with PAM (PAM-L, n =
      10). For cartilage and subchondral bone testing, rabbits from Sham and ACLT
      groups were harvested at 2, 4, 6, and 14 weeks. Rabbits were given PAM from the
      4th week after ACLT operation in PAM-S and PAM-L group, and were harvested at 6
      and 14 weeks, respectively. Trabecular characteristics and cartilage changes were
      detected using Micro-CT, safranin O and rapid green staining, respectively.
      Immunohistochemical staining for OPG and RANKL were also performed. OPG, RANKL,
      MMP-9 and TLR-4 expression was evaluated by western blot analysis. RESULTS: Micro
      CT and histology analyses indicated that PAM treatment for 2 or 10 weeks could
      completely prevent or reverse osteoarthritic subchondral bone loss and cartilage
      surface erosion. Immunohistochemistry and western blot analysis indicated that
      expression of OPG and RANKL increased, although RANKL expression increased more
      significantly than that of OPG. Therefore the ratio of OPG to RANKL was lower in
      the ACLT group. However, the ratio of OPG to RANKL in the PAM group was
      significantly higher than that in the ACLT group. Additionally, expression of MMP
      9 and TLR-4 were upregulated in the ACLT group and downregulated in the PAM
      treated groups. CONCLUSIONS: PAM can significantly inhibit and even reverse early
      osteoarthritic subchondral bone loss, thus alleviating the process of
      cartilaginous degeneration. The mechanisms involved may be associated with the
      upregulation of OPG expression, and downregulation of RANKL, MMP-9 and TLR-4
      expression.

PMID- 25377948
TI  - The involvement of the Toll-like receptor signaling and Nrf2-Keap1 pathways in
      the in vitro regulation of IL-8 and HMOX1 for skin sensitization.
AB  - In vitro gene profiling studies have associated the molecular pathways of Nrf2
      Keap1 and Toll-like receptor (TLR) signaling with skin sensitization. In this
      study, the role of these pathways in the regulation of protein biomarkers for
      skin sensitization was further elucidated using transient gene knock-down of key
      components of the signaling cascades in HaCaT cells after exposure to
      dinitrochlorobenzene (DNCB). The effect of targeting these pathways was
      established through evaluation of heme oxygenase1 (HMOX1) and interleukin (IL)-8
      production. These experiments showed that Nrf2 is not involved in regulating
      HMOX1 after exposure to DNCB, but that activation of TLR signaling moderates the
      expression of HMOX1. The regulation of IL-8 depended on Nrf2, but also on the
      Toll/interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon
      beta (TRIF) adaptor protein in TLR signaling. This study provides new insights
      into the regulation of HMOX1 and IL-8, but the exact regulating mechanisms remain
      to be further elucidated. 

PMID- 25377950
TI  - Role of the different sexuality domains on the sexual function of women with
      premature ovarian failure.
AB  - INTRODUCTION: Women with premature ovarian failure (POF) often manifest
      complaints involving different aspects of sexual function (SF), regardless of
      using hormone therapy. SF involves a complex interaction between physical,
      psychological, and sociocultural aspects. There are doubts about the impact of
      different complaints on the global context of SF of women with POF. AIM: To
      evaluate the percentage of influence of each of the sexuality domains on the SF
      in women with POF. METHODS: Cross-sectional study with 80 women with POF, matched
      by age to 80 women with normal gonadal function. We evaluated SF through the
      "Female Sexual Function Index" (FSFI), a comparison between the POF and control
      groups using the Mann-Whitney test. Component exploratory factor analysis was
      used to assess the proportional influence of each domain on the composition of
      the overall SF for women in the POF group. MAIN OUTCOME MEASURES: SF was
      evaluated using FSFI. Exploratory Factor Analysis for components was used to
      evaluate the role of each domain on the SF of women with POF. RESULTS: The FSFI
      score was significantly worse for women with POF, with a decrease in arousal,
      lubrication, orgasm, satisfaction, and dyspareunia. Exploratory factor analysis
      of SF showed that the domain with greater influence in the SF was arousal,
      followed by desire, together accounting for 41% of the FSFI. The domains with
      less influence were dyspareunia and lubrication, which together accounted for 25%
      of the FSFI. CONCLUSION: Women with POF have impaired SF, determined mainly by
      changes in arousal and desire. Aspects related to lubrication and dyspareunia
      complaints have lower determination coefficient in SF. These results are
      important in adapting the approach of sexual disorders in this group of women.

PMID- 25377951
TI  - Self and government regulations in all aspects of medical work: the new game in
      town.

PMID- 25377949
TI  - Severing of a hydrogen bond disrupts amino acid networks in the catalytically
      active state of the alpha subunit of tryptophan synthase.
AB  - Conformational changes in the beta2alpha2 and beta6alpha6 loops in the alpha
      subunit of tryptophan synthase (alphaTS) are important for enzyme catalysis and
      coordinating substrate channeling with the beta subunit (betaTS). It was
      previously shown that disrupting the hydrogen bond interactions between these
      loops through the T183V substitution on the beta6alpha6 loop decreases catalytic
      efficiency and impairs substrate channeling. Results presented here also indicate
      that the T183V substitution decreases catalytic efficiency in Escherchia coli
      alphaTS in the absence of the betaTS subunit. Nuclear magnetic resonance (NMR)
      experiments indicate that the T183V substitution leads to local changes in the
      structural dynamics of the beta2alpha2 and beta6alpha6 loops. We have also used
      NMR chemical shift covariance analyses (CHESCA) to map amino acid networks in the
      presence and absence of the T183V substitution. Under conditions of active
      catalytic turnover, the T183V substitution disrupts long-range networks
      connecting the catalytic residue Glu49 to the alphaTS-betaTS binding interface,
      which might be important in the coordination of catalytic activities in the
      tryptophan synthase complex. The approach that we have developed here will likely
      find general utility in understanding long-range impacts on protein structure and
      dynamics of amino acid substitutions generated through protein engineering and
      directed evolution approaches, and provide insight into disease and drug
      resistance mutations.

PMID- 25377952
TI  - Using pneumo-computerized tomography as a quantitative assessment of result in
      submucous fibrosis patients treated with surgical release and free flap
      reconstruction.
AB  - OBJECTIVE: This study investigates the efficacy of oral submucous fibrosis
      release and free flap reconstruction. STUDY DESIGN: Pneumo-computerized
      tomography (pneumo-CT) was used to evaluate postoperative changes in the buccal
      vestibular volume during maximum blowing. METHODS: From March 2003 to November
      2008, 9 patients underwent 18 microvascular flap reconstructions after oral
      submucous fibrosis release. The preoperative and postoperative buccal vestibular
      volumes were determined by capturing the air density in the selected region on CT
      images, which were composed of 0.75-mm-thick slices that were then summated using
      analysis software (Biomedical Imaging Resource; Mayo Foundation, Rochester, MN).
      RESULTS: Postoperative results were measured for a mean follow-up period of 15
      months (range, 6-36 mo). There was significant improvement in the interincisal
      distance from 12.44 (8.35) mm preoperatively to 32.56 (7.322) mm postoperatively
      (P = 0.000). There was an accompanying significant increase in the buccal
      vestibular volume from 5.66 (3.92) mL preoperatively to 9.38 (4.96) mL
      postoperatively on the right side (P = 0.032) and from 6.44 (4.20) mL
      preoperatively to 9.64 (4.65) mL postoperatively (P = 0.048) on the left side.
      CONCLUSIONS: Adequate release of the mucosa and resurfacing with a free flap can
      increase the interincisal distance and improve the maximal buccal vestibular
      volume. Air-contrast pneumo-CT studies demonstrate an improvement in buccal
      mucosal elasticity.

PMID- 25377953
TI  - Mandibular distraction combined with orthognathic techniques for the correction
      of severe adult mandibular hypoplasia.
AB  - BACKGROUND: Mandibular hypoplasia may result from congenital deformities or
      trauma or infection during the early stage of facial skeleton development.
      Deficiencies in the growth of the mandible can not only cause various degrees of
      facial deformity but also affect breathing and occlusal function. Here, we report
      our experiences with mandibular distraction combined with orthognathic surgical
      techniques for the treatment of severe adult mandibular hypoplasia. METHODS:
      Cephalometric analysis was conducted in all patients for quantitative evaluation.
      A computer-assisted surgical simulation was prepared before distraction.
      According to the simulation data, an operative osteotomy guide plate was designed
      and three-dimensionally printed with photosensitive resin. With the help of the
      guide plate, the osteotomy line was precisely placed. An internal distractor was
      then placed through an extraoral incision created under general anesthesia.
      Distraction began after 7 days of latency at the rate of 1 mm/d. After a 6- to 8
      month consolidation period, the distractor was removed. At the same time,
      genioplasty and/or subapical osteotomy was performed to correct the patient's
      crossbite and improve the facial contour for bilateral mandibular hypoplasia. For
      unilateral mandibular hypoplasia, a Le Fort I osteotomy was performed to correct
      the open bite on the affected side, whereas a mandibular outer cortex excision
      was performed on the unaffected side to improve lower facial symmetry. RESULTS:
      The mandible symmetry and chin protrusion were efficiently improved in all 36
      patients (mean age, 20.3 y). No facial nerve palsy was reported, nor were there
      complaints about postoperative facial scarring. The postoperative infection rate
      was 2.8%. The distance of lengthening was 26.2 (2.8) mm. The increased ramus
      length on the affected side was 18.9 (9.3) mm. At the end of the consolidation
      period (T2), the affected mandibular ramus length increased by 46.3% (23.6%) in
      unilateral distraction osteogenesis; however, it decreased by 18.6% (12.4%) after
      device removal (T3). For bilateral distraction osteogenesis, condylion-gonion
      increased by 34.0% (50.0%) in T2 but had no significant change in T3. CONCLUSION:
      Complicated mandibular hypoplasia can be well corrected with mandibular
      distraction combined with orthognathic surgery.

PMID- 25377954
TI  - Real-time ultrasound elastography for the differentiation of malignant and benign
      masses in the head and neck.
AB  - OBJECTIVES: The objective of this study was to evaluate head and neck masses with
      real-time elastography to differentiate malignant masses. MATERIALS AND METHODS:
      Between January 2011 and December 2012, a total of 51 patients with a palpable
      mass in the neck region were included in this study. Excisional histopathologic
      data were compared with elastographic results and Doppler ultrasonography.
      RESULTS: The study group comprised 27 males (52.9%) and 24 females (47.1%) (mean
      [SD] age, 41.47 [19.59] y; range, 4-80 y). Fourteen masses were malignant (27.5%)
      and 37 were benign (72.5%). Comparing the elastographic results of benign and
      malignant masses, elastographic scores of the malignant masses were significantly
      higher than those of the benign masses (P < 0.005).The elastographic scores were
      divided into 2 groups: 34 (91.9%) patients with the diagnosis of benign mass had
      the score of 1 to 2, whereas 9 (64.3%) patients with the diagnosis of malignant
      cases had the score of 3 to 4. There was a significant difference between the
      groups (P < 0.005).However, 2 squamous cell carcinomas (28.6%) and 1 lymphoma
      (8.1%) were diagnosed with an elastographic score of 1 (Table 2). This showed
      that even an elastographic score of 1 was not enough to issue a diagnosis of
      benign masses. CONCLUSIONS: With improvements in the device and increased
      experience, this modality can become a useful tool for the routine use. However,
      this modality cannot be used for screening to merely provide additional
      information about the nature of the masses.

PMID- 25377955
TI  - Neoadjuvant treatment combined with planned surgery in laryngeal function
      preservation for locally advanced pyriform sinus carcinoma.
AB  - OBJECTIVES: This study aimed to determine the efficacy and feasibility of
      preoperative radiotherapy with or without chemotherapy (XRT) followed by surgery
      of locally advanced pyriform sinus carcinoma. MATERIALS AND METHODS: We performed
      a retrospective study of 482 patients with T3 and T4 pyriform sinus carcinoma
      treated with curative intent between 1979 and 2008. The patients were divided
      into 4 groups according to different treatment patterns. RESULTS: The 5-year
      disease-special survival rate was 32%. Survival was best for the patients treated
      with surgery followed by XRT (41.1%) and with neoadjuvant XRT followed by surgery
      (39.4%), but it was worse with surgery only (27.1%) and XRT alone (23%). The
      disease-special survival was significantly different between the patients who
      accepted multidisciplinary therapy and those who accepted single therapy
      (P<0.001). The 5-year laryngeal function preservation survival rate of the
      patients with XRT followed by surgery was 13.6%, which was similar to those with
      XRT alone (16.2%), and superior to those who accepted surgery followed by XRT
      (3.8%) and surgery alone (0). Multivariate analysis results revealed that
      treatment pattern is an independent predictor of both overall and laryngeal
      function preservation survival rates (P < 0.001; hazard ratio, 0.56; 95%
      confidence interval, 0.44-0.71). Perioperative wound complications were not
      different among the patients in the 3 groups who accepted surgical treatment (P >
      0.05). CONCLUSIONS: The results suggested that neoadjuvant XRT followed by
      planned surgery was feasible with satisfactory oncological and functional
      outcomes.

PMID- 25377956
TI  - Does contribution of extended vomer flap to palatoplasty affects speech results.
AB  - Development of normal speech is the primary goal of successful palatoplasty. The
      purpose of this study was to determine the importance of the contribution of
      vomer flap to palatoplasty procedure for speech function. Eighty-one children who
      underwent 2 flap palatoplasty procedures for cleft palate repair between 2002 and
      2010 were retrospectively reviewed in 3 groups. Group 1 underwent palatoplasty
      without contribution of vomer flap. Group 2 underwent palatoplasty with standard
      dissection of vomer flap, whereas group 3 underwent palatoplasty with extended
      dissection of vomer flap. Speech function of the patients was evaluated using
      objective assessment tools such as nasopharyngoscopy and nasometer. Eighty-one
      children who underwent 2 flap palatoplasty were included in this study. The mean
      age at palatoplasty was 10.17 months, and mean length of follow-up was 72.33
      months. For most syllables, patients repaired using extended vomer flap
      demonstrated lower nasalance scores. Nasopharyngoscopic examination revealed
      velopharyngeal motility in 24 patients (80%) in group 1 and in 20 (83.3%) and 23
      (85.2%) patients in groups 2 and 3, respectively (P = 0.930). In velopharyngeal
      closure, there were only 5 patients (18.5%) in group 3, whereas there were 6
      patients (25.0%) for group 2 and 10 patients (33.3%) for group 1 with no closure
      (P = 0.311). Although most optimum results were observed in the group with
      extended dissection of the vomer flap, contribution of the extended vomer flap to
      the repair of the soft palate did not lead to significantly better speech
      results. 

PMID- 25377957
TI  - Thickness of labial alveolar bone overlying healthy maxillary and mandibular
      anterior teeth.
AB  - AIM: This study aimed to measure the thickness of labial bone overlying maxillary
      and mandibular anterior teeth and the distance between cementoenamel junction and
      bone crest in a Persian population. MATERIALS & METHODS: Two calibrated examiners
      evaluated tomographic data of 152 maxillary and 200 mandibular anterior teeth.
      Labial bone width was assessed at levels 1.0 to 5.0 mm apical to bone crest.
      Moreover, the distance between cementoenamel junction and bone crest was measured
      for both maxillary and mandibular teeth and its potential effect on the amount of
      labial bone thickness was assessed. RESULTS: One hundred-twenty nine maxillary
      central incisors, 77 lateral incisors, 70 canines, 105 mandibular central
      incisors, 103 lateral incisors and 81 canines were included for measurements. In
      maxilla, width of bone averaged 1.08mm, 1.11mm, and 1.3mm for central incisors,
      lateral incisors, and canines, respectively. Corresponding numbers for mandibular
      central incisors, lateral incisors, and canines were 0.74mm, 0.66mm and 0.40mm.
      High variation of cementoenamel junction to bone crest distance (range 0.5 to
      5.15 mm) was detected. The mean amount of labial bone width was not statistically
      different in patients with different distances between cementoenamel junction and
      bone crest; except for mandibular lateral incisors. CONCLUSION: The mean
      thickness of the labial alveolar bone overlying maxillary anterior teeth was
      found to be between 1 to 1.2 mm and between 0.5 to 0.8 mm for mandibular anterior
      teeth at the first 5 mm from bone crest in a Persian population.

PMID- 25377958
TI  - Verification of the reliability of the three-dimensional virtual presurgical
      orthodontic diagnostic protocol.
AB  - The precision of presurgical orthodontic diagnostic protocol plays a key role for
      the success of orthognathic surgery.Recently, the introduction of cone beam
      computed tomography and the development of digital technologies led to the
      possibility to create new virtual protocols of diagnostic protocol.The purposes
      of this study were to describe the virtual presurgical orthodontic diagnostic
      protocol experimented by the Orthodontics Department of the University of Milan
      and to assess its reliability by comparing it with the nonvirtual protocol.The
      study sample was a group of 18 adult patients who required surgical correction of
      skeletal asymmetric class II or III malocclusion: 9 of them were subjected to the
      virtual diagnostic protocol, whereas the other 9 were subjected to the
      traditional one. A comparison between the 2 methods was carried out by evaluating
      the degree of the discrepancy between setup and presurgical models in both
      groups. The values of maximum positive deviation, maximum negative deviation,
      mean deviation, and standard deviation that characterize the points of the
      superimpositions were considered.An optimal superimposition (>75%) between the
      scanning of the setup and presurgical models was obtained for all subjects except
      for 2 patients with asymmetry. The analysis of the punctual deviation variables
      did not show statistically significant differences between the techniques.The
      study suggested a high precision for both diagnostic protocols, and the
      reliability of the 2 methods is comparable. However, the virtual protocol has
      several advantages such as quantity of information obtainable, repeatability, and
      speed of execution. 

PMID- 25377959
TI  - Effects of lateral osteotomy on nasal sound intensity levels in patients who
      underwent rhinoplasty.
AB  - We investigated the effects of lateral osteotomy on nasal sound intensity levels
      in 34 patients who underwent rhinoplasty. Four groups were evaluated: group 1,
      preoperative rhinoplasty with lateral osteotomy (Preop-RPwithLO); group 2,
      postoperative rhinoplasty with lateral osteotomy (Postop-RPwithLO); group 3,
      preoperative rhinoplasty without lateral osteotomy (Preop-RPwithoutLO); and group
      4, postoperative rhinoplasty without lateral osteotomy (Postop-RPwithoutLO). By
      sound analysis, low-frequency (Lf; 500-1000 Hz), medium-frequency (Mf; 1-2 kHz),
      and high-frequency (Hf; 2-4 and 4-6 kHz) nasal sound intensities were defined. Mf
      left values of Postop-RPwithLO were significantly lower than those of Preop
      RPwithLO, and Mf-left values of Postop-RPwithoutLO were significantly higher than
      those of Postop-RPwithLO and Preop-RPwithoutLO. Hf-right values of Preop
      RPwithoutLO were significantly higher than those of Postop-RPwithLO and Postop
      RPwithoutLO. Hf-total values of Postop-RPwithoutLO were significantly lower than
      those of Preop-RPwithoutLO. Nasal airway width decreased and nasal sounds,
      especially Mf sound intensities, increased in the nonlateral osteotomy group
      (group 4). When lateral osteotomy is performed, the nasal air passage may be
      adjusted as required by the surgeon, the air passage in the nasal valve region
      may not be narrowed, and nasal sound intensities may decrease. During
      postoperative follow-ups, increased Mf and Lf nasal sound intensities should be
      considered for the narrowness of the nasal passage and lower patency of the nasal
      cavities. Nasal sound analysis is a noninvasive technique and can also be used to
      evaluate nasal patency in septoplasty and rhinoplasty patients and children and
      for cases in which official reports are needed in addition to acoustic rhinometry
      measurements. 

PMID- 25377960
TI  - Radiologic and surgical findings in chronic suppurative otitis media.
AB  - Our aim in this study was to evaluate the efficiency of preoperative temporal
      bone computed tomography (CT) in detecting pathologic conditions in patients with
      chronic suppurative otitis media (CSOM). The intraoperative findings and temporal
      bone CT results of 350 patients who were diagnosed with CSOM between September 1,
      2010, and June 1, 2013, were compared. Comparison parameters were as follows: the
      presence of cholesteatoma, erosion of the outer ear bone canal, erosion of the
      middle ear chain, erosion of the dural plate, erosion of the lateral semicircular
      canal, erosion of the sigmoid sinus wall, and dehiscence of the facial canal. The
      contribution of CT was limited in showing the outer ear canal destruction, dural
      plate destruction, facial canal destruction, lateral semicircular canal
      destruction, and destruction of the sigmoid sinus wall. However, CT was more
      sensitive in detecting cholesteatoma and erosion of the ossicular chain. These
      results indicate that preoperative CT of patients with CSOM serves as an
      important guide for otolaryngologists, although there are limitations in the
      evaluation of the CT results. 

PMID- 25377961
TI  - Early paper patching versus observation in patients with traumatic eardrum
      perforations: comparisons of anatomical and functional outcomes.
AB  - The purpose of this study was to compare the outcomes of patients with acute
      tympanic membrane perforation after spontaneous healing and paper-patching
      procedure. METHODS DESIGN, SETTING, AND PARTICIPANTS: In this study, we performed
      a retrospective chart review with a prospective follow-up in 63 patients with
      tympanic membrane perforations. The patients undergoing a paper-patching
      procedure were assigned to group 1 (n = 33), whereas the patients that healed
      spontaneously were included in group 2 (n = 30). Retrospective analyses of the
      otoscopic examination findings and audiometric test results of the groups at the
      sixth-week follow-up were compared. RESULTS: Eardrum healing was achieved in
      90.9% of the patients in group 1 and 76.7% of the patients in group 2 at the
      sixth week (P > 0.05). The mean values of air conduction were significantly
      improved, and the air-bone gap was markedly decreased in the patients treated
      with paper patching, when compared with the patients in group 2 (P < 0.001). The
      area of perforation was found to be inversely related to the healing success.
      CONCLUSIONS: Early intervention by paper patching, which is a readily applicable
      procedure, may be offered to the patients with acute perforation of the tympanic
      membrane, because of the slightly better closure rates and significantly higher
      hearing functions when compared with simple observation.

PMID- 25377962
TI  - Outcome of comminuted mandibular fracture repair using an intraoral approach for
      osteosynthesis.
AB  - PURPOSE: Traditionally, the treatment of comminuted mandibular fractures involves
      both closed and open reduction. However, modern treatment principles increasingly
      tend toward open reduction and internal fixation to shorten oro-functional
      rehabilitation. Although this method increasingly gained popularity to date, a
      controversy regarding the extraoral versus the intraoral surgical approach still
      exists. The current study aimed to objectively evaluate the outcome of comminuted
      mandibular fracture treatment involving open reduction and internal fixation
      using an intraoral approach. PATIENTS AND METHODS: Consecutive patients treated
      at the Department of Cranio-Maxillofacial and Oral Surgery, University Hospital
      of Zurich, between 2005 and 2012 were included. Demographic, presurgical,
      perisurgical, and postsurgical data were tabulated and statistically evaluated
      using the chi test and the Mann-Whitney U test. RESULTS: Forty-five patients
      could be included. Excellent postoperative results were seen in 84% (38 patients)
      of the total cohort. Postoperative complications were seen in 16% (7 patients).
      These 7 patients had the following complications: wound dehiscence (7% [n = 3]),
      osteomyelitis (7% [n = 3]), abscess development (4% [n = 2]), bone necrosis (2%
      [n = 1]), and severe nonocclusion (2% [n = 1]). CONCLUSION: Present data showed
      that the intraoral approach for open reduction and internal fixation in
      comminuted mandibular fractures represents a comparable surgical technique
      regarding fracture repositioning and occlusal rehabilitation. Considerably, the
      risk of concomitant neurovascular damage or even facial scarring, as demonstrated
      in the extraoral approach, can be neglected by using this technique.
      Nevertheless, each case has to be judged on its own accord as to which technique
      can best treat the underlying fracture.

PMID- 25377963
TI  - Management of frontal sinus fractures: treatment modality changes at a level I
      trauma center.
AB  - The optimal management of frontal sinus fractures remains controversial, and
      previously accepted indications for surgical intervention are being challenged.
      The goals of this study were to determine how frontal sinus fracture management
      has changed at a single institution across multiple disciplines and to evaluate
      the long-term outcomes of operative and nonoperative treatment
      modalities.Patients treated for a frontal sinus fracture at Stanford Hospital and
      Clinics between June 1998 and June 2009 were included in the study. Inpatient
      records, clinic notes, operative reports, and radiographic studies were reviewed.
      The patients were invited for a follow-up clinic visit, physical examination, and
      focused sinus computed tomography. For a period of 11 years, 124 patients were
      treated for a frontal sinus fracture by physicians from 3 surgical
      subspecialties: otolaryngology, plastic surgery, and neurosurgery. A low short
      term complication rate was observed (5.6%), and there was a trend toward
      nonsurgical management within the study population. Ten patients returned for a
      long-term follow-up. Of these, the 2 patients who underwent cranialization
      experienced as many or more long-term complications compared with the patients
      treated by other modalities. These complications included abnormal frontal bone
      contour with bony discontinuity and altered sensation in the distribution of the
      trigeminal nerve.The demonstrated trend toward nonsurgical management of frontal
      sinus fractures seems to be safe. In the limited group of patients who returned
      for follow-up, more long-term complications were observed in the patients who
      underwent cranialization. However, a larger long-term follow-up cohort will be
      necessary to elucidate the relationship between treatment modality and long-term
      outcomes and complications. 

PMID- 25377964
TI  - Ancillary procedures necessary for translational research in experimental
      craniomaxillofacial surgery.
AB  - INTRODUCTION: Swine are often regarded as having analogous facial skeletons to
      humans and therefore serve as an ideal animal model for translational
      investigation. However, there is a dearth of literature describing the pertinent
      ancillary procedures required for craniomaxillofacial research. With this in
      mind, our objective was to evaluate all necessary procedures required for
      perioperative management and animal safety related to experimental
      craniomaxillofacial surgical procedures such as orthotopic, maxillofacial
      transplantation. METHODS: Miniature swine (n = 9) were used to investigate
      perioperative airway management, methods for providing nutrition, and long
      dwelling intravenous access. Flap perfusion using near-infrared laser angiography
      and facial nerve assessment with electromyoneurography were explored. RESULTS:
      Bivona tracheostomy was deemed appropriate versus Shiley because soft, wire
      reinforced tubing reduced the incidence of tracheal necrosis. Percutaneous
      endoscopic gastrostomy tube, as opposed to esophagostomy, provided a reliable
      route for postoperative feeding. Femoral venous access with dorsal tunneling
      proved to be an ideal option being far from pertinent neck vessels. Laser
      angiography was beneficial for real-time evaluation of graft perfusion. Facial
      electromyoneurography techniques for tracing capture were found most optimal
      using percutaneous leads near the oral commissure.Experience shows that ancillary
      procedures are critical, and malpositioning of devices may lead to irreversible
      sequelae with premature animal death. CONCLUSIONS: Face-jaw-teeth transplantation
      in swine is a complicated procedure that demands special attention to airway,
      feeding, and intravascular access. It is critical that each ancillary procedure
      be performed by a dedicated team familiar with relevant anatomy and protocol.
      Emphasis should be placed on secure skin-level fixation for all tube/lines to
      minimize risk for dislodgement. A reliable veterinarian team is invaluable and
      critical for long-term success.

PMID- 25377965
TI  - Accuracy assessment of image-based surface meshing for volumetric computed
      tomography images in the craniofacial region.
AB  - BACKGROUND: Three-dimensional printing and computer-assisted surgery demand a
      high-precision three-dimensional mesh model created from computed tomography (CT)
      imaging data using an image-based meshing algorithm. We aimed to evaluate the
      three-dimensional geometric accuracy of surface meshes produced from CT images
      with commercially available software packages. METHODS: The CT images were
      acquired for 3 human dry skulls and 10 manufactured plastic skulls. Four
      commercially available software packages were used to produce the surface meshes
      in stereolithography (STL) file format. These CT-based STL surface meshes were
      registered and compared with three-dimensional optical-scanned reference mesh
      surface for evaluating the accuracy of the STL mesh produced with each software
      package. RESULTS: The surface geometries produced by the CT-image-based meshing
      process were all relatively accurate; differences from the three-dimensional
      optical-scanned data were in the voxel or subvoxel range. However, when
      comparisons with the three-dimensional optical-scanned surface data were
      performed in individual anatomic regions, we found significantly different
      accuracies of the CT-based STL surface meshes produced by the different software
      packages. CONCLUSIONS: We found that all 4 software packages showed reasonably
      good meshing accuracies for clinical use. However, the range of errors inherent
      in the CT-image-based meshing process demands that caution should be taken in
      selecting and manipulating the software to avoid potential errors in specific
      clinical applications.

PMID- 25377966
TI  - Platelet-rich fibrin plays a role on healing of acute-traumatic ear drum
      perforation.
AB  - OBJECTIVE: Our objective was to demonstrate the effects of platelet-rich fibrin
      (PRF) for the healing of acute ear drum perforation. METHODS: Thirty-two patients
      with acute traumatic ear drum perforations were randomly separated into 2 groups.
      In group 1 (n = 14), PRF was used for the repair of ear drum perforation; in
      group 2 (n = 18), we did not make any intervention. RESULTS: At initial
      inspection, perforation sizes were measured as 10.93 +/- 3.58 mm in group 1 and
      10.05 +/- 4.02 mm in group 2. After 1 month, perforation sizes were 1.35 +/- 2.53
      mm in group 1 and 4.44 +/- 3.34 mm in group 2 (P < 0.01). In the study group, the
      rate of ear drum closure was 64.3% and in the control group it was 22.2% (P <
      0.05). CONCLUSION: Here we found that PRF is a biomaterial that quickens the
      healing of ear drum which is autogenous and simply prepared.

PMID- 25377967
TI  - Epitheloid hemangioma treated with naproxen sodium.
AB  - Epitheloid hemangioma (EH) is a vascular tumor characterized by an epithelioid
      endothelial cell. Predominantly affecting the head and neck, fewer than 30 cases
      involving the scrotum have been published. As this represents an extremely rare
      entity, a multitude of anecdotal treatment modalities have been utilized
      including systemic/intralesional steroid therapy, radiotherapy, and chemical
      therapy. However, surgical excision remains the most widely accepted treatment
      option.We present a case of EH of the scrotum in a 14-year-old male patient that
      regressed after treatment with naproxen sodium. To the best of our knowledge,
      this represents the first reported case of scrotal EH regression following
      treatment with naproxen sodium. LEVEL OF EVIDENCE: V.

PMID- 25377968
TI  - Comparison of silkworm-cocoon-derived silk membranes of two different thicknesses
      for guided bone regeneration.
AB  - The objective of this study was to compare the effectiveness of silk membranes
      (SMs) of different thicknesses for guided bone regeneration. Two kinds of SMs
      were prepared (SM1: 0.01 mm thickness, SM2: 0.5 mm thickness). Before use in
      animal experiments, scanning electron microscope images were taken to examine the
      gross morphology of each membrane. Ten New Zealand white rabbits were used for
      this study. Bilateral round-shaped defects were created in the parietal bone
      (diameter: 8.0 mm) and each defect was covered with SM1 or SM2. Animals were
      killed at 4 weeks and 8 weeks. Bone regeneration was analyzed in each specimen by
      micro-computed tomography (MU-CT) and histological analysis. In the MU-CT
      analysis, the average amount of newly formed bone in the SM2 group was greater
      than that in the SM1 group. There was a significant difference at 4 weeks after
      surgery (P = 0.004). In the histological analysis, the amount of formed lamellar
      bone was much greater in the SM2 group than in the SM1 group at 8 weeks after
      surgery (P = 0.021). In conclusion, the thick SM was much more effective for bone
      regeneration of bone defects than the thin SM. 

PMID- 25377969
TI  - Nasal reconstruction with the paramedian forehead flap using the aesthetic
      subunits principle.
AB  - Reconstruction of nasal defects is challenging because it requires covering skin,
      supporting framework, and lining. Traditionally, the forehead flaps are
      transferred in 2 stages; however, it can be accomplished in a single stage or in
      3 stages. Few published studies are available about the paramedian forehead flap
      using the intermediate stage (3-stage) and the aesthetic subunits principle. The
      purpose of this study is to evaluate the use of the paramedian forehead flap in 2
      and 3 stages for nasal reconstructions, highlighting the indications,
      complications, and technical details and evaluating the patient's satisfaction
      through a questionnaire about the quality of life (Derriford Appearance Scale
      24). A retrospective review was performed between 2011 and 2013 for a consecutive
      series of 11 patients who underwent nasal reconstructions using the paramedian
      forehead flap in 2 or 3 stages. All preoperative and postoperative data were
      collected, and outcomes were also assessed through a questionnaire about the
      patients' postoperative quality of life. The causes of nasal lesions varied among
      skin cancer, trauma, and infection. Two-stage paramedian forehead flap
      reconstruction was performed upon 4 patients, whereas the 3-stage reconstruction
      was performed for 7 patients. Of the 10 survey respondents, 6 were highly
      satisfied (score of 11-27), and 4 were moderately satisfied (score of 28-44),
      whereas no one was dissatisfied after his/her surgical nasal reconstruction
      procedure. Whether the approach is accomplished in 2 or 3 stages, all areas of
      the reconstructed nose must be firmly supported. Applying the nasal subunits
      principle seems to contribute to an overall satisfied population in our study,
      according to the score obtained by the questionnaire about quality of life. 

PMID- 25377970
TI  - A new design of facial artery perforator flaps for the reconstruction of small-
      to medium-sized intraoral defects.
AB  - AIM: The aim of this study was to investigate the reliability and outcomes of a
      new design of facial artery perforator flaps, extending from the angle of the
      mouth to the border of the mandible, for the reconstruction of small- to medium
      sized intraoral defects. PATIENTS AND METHODS: The technique had been used in 23
      patients between February 2009 and August 2012. The locations of intraoral
      defects included the tongue, the floor of the mouth, the inferior gingival
      mucosa, and the sublingual gland. All flaps were monitored for complications
      including skin loss and ischemia. The functions of appearance, swallowing, and
      speech were assessed 6 months after operation with the University of Washington
      Quality of Life Questionnaire. RESULTS: All flaps presented with satisfactory
      results except for one, which demonstrated superficial tip necrosis that settled
      after conservative treatment. The follow-up period ranged from 6 to 12 months,
      and 1 patient died as a result of pulmonary metastasis, and 3 patients underwent
      second surgery because of local tumor recurrence (2patients) and cervical
      recurrence (1 patient). Nineteen patients were assessed with the University of
      Washington Quality of Life Questionnaire, and the mean (SD) scores of appearance,
      swallowing, and speech were 57.89 (14.45), 83.68 (19.98), and 81.58 (23.16),
      respectively. CONCLUSIONS: This design of facial artery perforator flaps could
      provide an efficient and cost-effective method for reconstruction of small- to
      medium-sized intraoral defects with a low surgical morbidity and satisfactory
      levels of quality of life.

PMID- 25377971
TI  - Frontal bone fractures.
AB  - The aim of this retrospective study was to evaluate the epidemiology, treatment,
      and complications of frontal bone fractures associated, or not, with other facial
      fractures. This evaluation also sought to minimize the influence of the surgeon's
      skills and the preference for any rigid internal fixation system. The files from
      3758 patients who attended the Oral and Maxillofacial Surgery Department of the
      School of Dentistry of Ribeirao Preto, University of Sao Paulo, from March 2004
      to November 2011 and presented with facial trauma were scanned, and 52 files were
      chosen for the review. Eleven (21.15%) of these patients had pure fractures of
      the frontal bone, and trauma incidence was more prevalent in men (92.3%), whites
      (61.53%), and adults (50%). Despite the use of helmets at the moment of the
      trauma, motorcycle crashes were the most common etiological factor (32.69%).
      Fracture of the anterior wall of the frontal sinus with displacement was the main
      injury observed (54.9%), and the most common treatment was internal fixation with
      a plate and screws (45.09%). Postoperative complications were observed in 35.29%
      of the cases. The therapy applied was effective in handling this type of
      fracture, and the success rate was comparable to that reported in other published
      studies. 

PMID- 25377972
TI  - Single-stage reconstruction of a full-thickness alar defect using a folded
      nasolabial flap combined with a redundant skin turnover flap.
AB  - BACKGROUND: The reconstructive strategy for full-thickness nasal skin defects
      should include recreation of a cutaneous cover, support, and internal nasal
      lining. The most challenging aspect of this procedure is provision of the nasal
      lining. These reconstructions typically require a 2-step process. Satisfactory
      nasal skin reconstruction in a single operation is ideal. OBJECTIVE: We used a
      folded nasolabial flap combined with a turnover flap for reconstruction of full
      thickness alar defects. METHODS: The donor material of the lining flap was a
      combination of the distal portion of the nasolabial flap and redundant skin
      resected during its transposition. The redundant skin flap was turned upside
      down, with the skin surface inside the nasal cavity. The remaining portion of the
      defect was covered with a folded nasolabial flap. RESULTS: This procedure was
      successful in all 5 patients. All flaps survived completely without evidence of
      necrosis or narrowing of airways. Aesthetic concerns, including effacement of the
      nasofacial sulcus, were minor. CONCLUSION: This method has the advantage of
      providing well-vascularized tissue of appropriate color, texture, and thickness
      for external coverage, as well as a satisfactory internal lining in a single
      stage procedure.

PMID- 25377973
TI  - Preliminary study of diffusion-weighted imaging and magnetic resonance
      spectroscopy imaging in Kimura disease.
AB  - In this study, we evaluated the value of diffusion-weighted imaging (DWI) and
      magnetic resonance (MR) spectroscopy imaging (MRSI) combined with computed
      tomography (CT) and conventional MR imaging (MRI) in the diagnosis of Kimura
      disease (KD). The clinical data and CT and MRI findings of 5 patients with KD
      proven by histopathologic examination were retrospectively reviewed. Diffusion
      weighted imaging and MRSI were performed at 1.5 T in 3 patients with KD. Apparent
      diffusion coefficient (ADC) values and the choline/creatine ratio of the lesions
      were compared with those of the contralateral normal parotid glands. All imaging
      results were compared with histopathologic findings. The typical features of KD
      were subcutaneous lesions, continuously infiltrative parotid lesions with or
      without intraparotid lymphadenopathies, and reactive cervical lymphadenopathies
      on CT and conventional MRI. On DWI, the ADC values of all subcutaneous and
      infiltrative parotid lesions were higher compared to those of normal parotid
      glands, and the ADC values of reactive lymphadenopathies were lower compared to
      both. The choline/creatine levels of subcutaneous and infiltrative parotid
      lesions were slightly higher than those of normal parotid glands. In conclusion,
      DWI and MRSI offer valuable information that may be characteristic of KD, which
      can highly suggest the diagnosis of KD when combined with morphological imaging. 

PMID- 25377974
TI  - DNA damage in children with obstructive adenotonsillar hypertrophy.
AB  - The objective of this prospective, controlled study was to evaluate oxidative DNA
      damage in children with obstructive adenotonsillar hypertrophy. This study
      included 30 patients with obstructive adenotonsillar hypertrophy (male/female
      ratio, 3:2; age range, 3-9 y) scheduled to undergo tonsillectomy and
      adenoidectomy and 25 control subjects of similar age and sex with no
      adenotonsillar disease or airway obstruction. Urine and blood samples were
      obtained from each child for 8-hydroxy 2-deoxyguanosine (8-OhdG) and
      malondialdehyde (MDA) concentrations. There were significant differences in
      leukocyte (3.28 [0.69/10] vs 0.70 [0.15/10] dG) and urine 8-OhdG (8.22 [2.27/10]
      vs 5.26 [1.3/10] dG) levels in patients with obstructive adenotonsillar
      hypertrophy and healthy subjects (P < 0.001 for both). Plasma (2.98 [1.31] vs
      1.14 [0.64] MUM) and urine (1.77 [0.84] vs 0.56 [0.32] MUM) MDA levels were also
      different (P < 0.001 for both). There were positive correlations between 8-OhdG
      in leukocyte DNA and plasma MDA (r = 0.648, P < 0.001) and between levels of
      urine 8-OhdG excretion and urine MDA (r = 0.588, P < 0.001). The DNA damage in
      children with adenotonsillar hypertrophy should be kept in mind, but further
      studies must be done with larger patient groups. 

PMID- 25377975
TI  - The evaluation of morphometry of nasal bone and pyriform aperture using
      multidetector computed tomography.
AB  - INTRODUCTION: The aim of this study was to measure nasal bone (NB) and pyriform
      aperture (PA), morphometrically. Besides, the different types of NB and PA were
      classified and determined the sexual differences. MATERIALS AND METHODS: Our
      study was performed on 120 (60 women, 60 men) multidetector computed tomography
      images obtained from patients who underwent radiologic examination in the
      Department of Radiology of Meram Faculty of Medicine, Necmettin Erbakan
      University. The right, left, and median heights of NB; the superior and inferior
      widths of NB; the width of PA; and the distance between rhinion and anterior
      nasal spine (as the height of PA) were measured. Frontonasal and internasal
      angles were also determined. All data were analyzed statistically using Student's
      t-test. RESULTS: The other data of men were higher than of women except for the
      superior and inferior widths of NB and the frontonasal angle. We also determined
      the ratio of the height of PA to the height of NB on median plane and the ratio
      of the height of PA to the width of PA. They were found less than 2.0 in 64.2%
      and 100% of the cases, respectively. The NB and PA were classified into 8 and 7
      different types, respectively. CONCLUSIONS: The knowledge of the morphometric
      data and different types of the NB and PA is essential for sex determination, all
      surgical procedures related to this area, and nasal reconstructions.

PMID- 25377976
TI  - Subtemporal-anterior transtentoral approach to middle cranial fossa microsurgical
      anatomy.
AB  - This study aimed to describe the topography of inferior and external dura mater
      of the middle cranial fossa through subtemporal-anterior transpetrosal approach
      and discuss the feasibility of improving the approach. Eight formalin-fixed adult
      cadaveric heads were studied, with the bones milled away in the lateral triangle
      region of the petrous bone, Kawase rhombus region, and inner triangle region of
      the petrous apex. The distances between the targets in these regions, as well as
      the angles after the dissection of zygomatic arch, were measured, and then the
      exposed petroclival and retrochiasmatic areas were observed under the microscope.
      There were significant variations in the distances between targets in the 3
      milled regions among the specimens. After the dissection of zygomatic arch, the
      surgical view got an average increase of 12 degrees. The subtemporal anterior
      transpetrosal approach, as an improved subtemporal approach, can expose the
      lesions optimally, causing no injury to the hearing and reducing injuries to
      temporal lobe. On the other hand, the lateral bone of the petrous parts of the
      temporal bone is removed so as to improve the view to the retrochiasmatic area
      and expand the operative field. 

PMID- 25377977
TI  - Suggested modification of the technique coronectomy for lower third molar.

PMID- 25377978
TI  - Epistaxis and Staphylococcus aureus colonization in the nasal vestibule: is it a
      cause or consequence?
AB  - The aim of this study was to investigate the relation between epistaxis and nasal
      colonization of Staphylococcus aureus in a population of patients with recurrent
      epistaxis. A total of 361 men and women were recruited, 245 patients with
      epistaxis (114 had crusting in the nasal vestibule; 131 did not) and 116 control
      subjects. A microbiology swab was taken from the anterior nasal cavity of each
      subject. Staphylococcus aureus was found to be more common in the epistaxis group
      when compared with the control group with a percentage of 31.8% and 4.3%,
      respectively (P < 0.05). There was no difference in the prevalence of S. aureus
      between the crust and non-crust groups (P > 0.05). When positive cultures were
      grouped and compared according to season, it was observed that the positive
      culture with epistaxis was much higher (44.82 %) in the autumn period.
      Staphylococcus aureus colonization in the nasal vestibule is more likely to be
      observed in individuals who have recurrent epistaxis than in those who do not
      have. It seems that this colonization may have a role in the etiology of
      epistaxis. However, with an altered medium of the nasal vestibule after each
      epistaxis period, it is also possible to speculate that this colonization is may
      be the consequence of epistaxis itself. 

PMID- 25377979
TI  - A simple score for evaluation of the complexity of third-molar extractions.
AB  - OBJECTIVES: This article proposes a simple preoperative score to evaluate the
      complexity of tooth extractions of the third mandibular molar and to estimate the
      time involved. STUDY DESIGN: We consider 11 factors (demographic, anatomic, and
      radiologic) that favor the surgery and that can be identified through standard
      clinical and radiologic examinations. The number of favorable factors (NFF)
      relative to each patient constitutes his/her score. The analysis of 1500
      extractions performed by various surgeons with experience from 2 to 25 years
      evidences a quadratic inverse correlation between NFF and the time required for
      the surgery. RESULTS: The shape of the time distribution suggests the existence
      of 3 major classes of patients characterized by time of 4 to 10 minutes, 11 to 20
      minutes, and 21 to 40 minutes. The corresponding NFF brackets, as identified by
      their frequency distributions and validated by the receiver operating
      characteristic curve method, are 5 to 11 (mean [SD], 6.8 [1.6]), 2 to 4 (3.3
      [1.3]), and 0 to 1 (0.8 [1.0]), respectively. CONCLUSIONS: Our results show the
      good performance of this score as a predictor of the surgical time and its
      applicability in daily practice regardless of operator experience, background,
      and level of surgical ability.

PMID- 25377980
TI  - Caries management by risk assessment in a cleft and craniofacial center.
AB  - Patients with craniofacial anomalies have an increased incidence of dental
      caries. The prevention program "Caries Management By Risk Assessment" (CAMBRA)
      has been previously validated but has not yet been introduced at a widespread
      level in a medical setting, particularly for this high-risk population.In this
      cross-sectional study, we aimed to evaluate the feasibility of implementing
      CAMBRA during the medical visit at an institutional tertiary care center, which
      treats children with craniofacial anomalies. The study included 161 participants
      aged 1 to 18 years. Patients and parents received a personalized educational
      session, toothbrushing tutorial, and fluoride varnish application. We assessed
      the prevalence of dental caries, caries risk factors, and knowledge of oral
      hygiene in this patient population.The overall caries prevalence in this group
      was higher than average (57% compared with 42%, according to the Centers for
      Disease Control and Prevention). The most prevalent risk factors were
      developmental delay, deep pits/fissures, low socioeconomic status, orthodontic
      appliances, and carbohydrate snacks. The greatest predictors of dental caries
      were having 1 or more risk factors and having low socioeconomic status. In
      summary, children with craniofacial anomalies were at high risk for dental
      caries, with high rates of risk factors and low rates of preventive factors.Our
      findings revealed that basic oral hygiene standards are not being met in this
      high-risk population, highlighting the need for implementation of protocols such
      as CAMBRA. The results of this study can aid healthcare workers in craniofacial
      centers and children's hospitals to improve the understanding of oral hygiene and
      dental care of their patients. 

PMID- 25377981
TI  - Pachydermoperiostosis: aesthetic treatment of prematurely aging face with
      facelift and botulinum toxin a.
AB  - Pachydermoperiostosis is a rare syndrome that hinders patients' quality of life
      thru its aesthetics manifestations and functional obstacles. Many techniques for
      addressing and correcting aesthetic defects associated with pachydermoperiostosis
      have been introduced, including facelift surgery. This case presentation includes
      treatment of facial pachydermoperiostosis and restoration of facial aesthetics
      via treatment with facelift, skin muscle excision, and botulinum toxin A. 

PMID- 25377982
TI  - Delayed cerebrospinal fluid rhinorrhea four years after gamma knife surgery for
      juvenile angiofibroma.
AB  - Juvenile angiofibroma (JA) is a highly vascularized tumor that often recurs or
      regrows. Recently, gamma knife surgery (GKS) was attempted on unresectable or
      remnant JA. We experienced a JA case that developed cerebrospinal fluid (CSF)
      rhinorrhea 4 years after GKS. Two surgical excisions using midfacial degloving
      approach were performed before GKS. After radiosurgery, the tumor was controlled,
      and no early complications were observed. However, 4 years after, intractable CSF
      leakage developed as a late complication, and we thus performed 4 subsequent
      endoscopic surgical repairs. The CSF leakage is very rare but can occur as a late
      complication of GKS and should be treated aggressively. 

PMID- 25377983
TI  - Primary malignant mucosal melanoma of the nasopharynx: an unusual cause of
      unilateral hearing loss.
AB  - There are many causes of unilateral hearing loss, and making the correct
      differential diagnosis, especially in elderly patients, is difficult. A primary
      malignant mucosal melanoma of the nasopharynx is extremely rare and can cause a
      variety of symptoms. Hearing loss, as a presenting symptom of mucosal malignant
      melanoma of the nasopharynx, has not yet been defined in the literature. Herein,
      we report a case of primary mucosal malignant melanoma of the nasopharynx
      presented with unilateral hearing loss in a 70-year-old man. 

PMID- 25377984
TI  - General and stomatologic aspects of bardet-biedl syndrome.
AB  - OBJECTIVE: The purpose of this study is to present a clinical report of a patient
      with Bardet-Biedl syndrome, aiming to help the dentist to identify the general
      aspects, systemic changes, alterations. CLINICAL REPORT: Bardet-Biedl syndrome is
      defined as a genetic disorder of autosomal recessive condition; this case is a
      male patient, 20 years old. The general features presented by the patient were
      strabismus, polydactyly, hypogonadism, obesity, cognitive impairment, and
      autistic behavior. Dentally, this patient presents with hypotonic face, high
      arched palate, dental crowding, unilateral crossbite, and difficulty in cleaning
      but with good-quality oral health. CONCLUSIONS: Many patients with this syndrome
      have compromised oral hygiene, difficulty in addressing dental cases,
      developmental delay, and autistic behavior. Thus, it is important to pay
      attention to these early children from an early age and encourage preventive
      approach.

PMID- 25377985
TI  - Salivary duct carcinoma in the mandible.
AB  - We reported 1 case of salivary duct carcinoma (SDC) in the mandible. The patient
      complained of pain and a growing mass in the right submandibular area for
      approximately 2 months. On clinical examination, there was a mass under the right
      angle of the mandible with a size of approximately 3 * 3 cm, a smooth surface, a
      poor activity, and a hard texture. Panoramic radiograph revealed poorly
      circumscribed area. Computed tomography presented mandible central destruction.
      Biopsy examination showed a malignant tumor that originated in the central
      epithelium of the mandible. An operation of unilateral selective neck dissection
      and mandible subtotal ectomy was performed. Postoperative pathology reported SDC.
      The patient received postoperative radiation and stayed alive at last follow-up
      without disease recurrence. Ablative resection and postoperative radiotherapy
      were the standard treatment stratagem for SDC, but trastuzumab therapy might play
      a key role in treating the disease in future.

PMID- 25377986
TI  - Radiofrequency versus electrocautery for inferior turbinate hypertrophy.
AB  - AIM: The aims of this study were to compare radiofrequency tissue reduction
      (RFTR) and electrocautery (EC) techniques by assessing preoperatively and 8 weeks
      postoperatively the visual analog scale (VAS), inspiratory peak flowmetry (IPF),
      and magnetic resonance imaging (MRI) volume measurement of the inferior turbinate
      and to see whether EC still stands as a valid treatment of inferior turbinate
      hypertrophy. METHODS: A total of 36 patients were included in the study. An equal
      number of patients were chosen randomly from 2 groups. Inferior turbinate volumes
      measured by MRI, IPF, the VAS, and the Sinonasal Outcome Test-20 were used to
      determine the efficacy of treatment and to compare the 2 groups. RESULTS:
      Postoperative IPF increase, VAS score decrease, and Sinonasal Outcome Test-20
      score decrease were statistically more significant in the EC group, compared with
      the RFTR group. Although statistically not significant, postoperative inferior
      turbinate MRI volume decrease was more evident in the EC group when compared with
      the RFTR group. CONCLUSIONS: Both RFTR and EC techniques could be used as an
      effective treatment of choice for inferior turbinate hypertrophy, and EC
      technique is superior to RFTR technique to achieve high efficiency.

PMID- 25377987
TI  - The development of auditory perception in children after auditory brainstem
      implantation.
AB  - Auditory brainstem implants (ABIs) can provide useful auditory perception and
      language development in deaf children who are not able to use a cochlear implant
      (CI). We prospectively followed up a consecutive group of 64 deaf children up to
      12 years following ABI surgery. The etiology of deafness in these children was:
      cochlear nerve aplasia in 49, auditory neuropathy in 1, cochlear malformations in
      8, bilateral cochlear postmeningitic ossification in 3, neurofibromatosis type 2
      in 2, and bilateral cochlear fractures due to a head injury in 1. Thirty-five
      children had other congenital nonauditory disabilities. Twenty-two children had
      previous CIs with no benefit. Fifty-eight children were fitted with the Cochlear
      24 ABI device and 6 with the MedEl ABI device, and all children followed the same
      rehabilitation program. Auditory perceptual abilities were evaluated on the
      Categories of Auditory Performance (CAP) scale. No child was lost to follow-up,
      and there were no exclusions from the study. All children showed significant
      improvement in auditory perception with implant experience. Seven children (11%)
      were able to achieve the highest score on the CAP test; they were able to
      converse on the telephone within 3 years of implantation. Twenty children (31.3%)
      achieved open set speech recognition (CAP score of 5 or greater) and 30 (46.9%)
      achieved a CAP level of 4 or greater. Of the 29 children without nonauditory
      disabilities, 18 (62%) achieved a CAP score of 5 or greater with the ABI. All
      children showed continued improvements in auditory skills over time. The long
      term results of ABI surgery reveal significant auditory benefit in most children,
      and open set auditory recognition in many.

PMID- 25377988
TI  - The Gateway Hypothesis of substance abuse: developmental, biological and societal
      perspectives.
AB  - The Gateway Hypothesis describes how tobacco or alcohol use precedes marijuana
      and other illicit drug use. We review the epidemiological data, explore the
      underlying molecular mechanisms in mice and discuss the societal implications of
      the hypothesis, including the use of e-cigarettes by young people. CONCLUSION:
      Our mouse model identifies biological processes underlying the hypothesis,
      showing that nicotine is a gateway drug that exerts a priming effect on cocaine
      through increased global acetylation in the striatum.

PMID- 25377990
TI  - A flux-gradient system for simultaneous measurement of the CH4, CO2, and H2O
      fluxes at a lake-air interface.
AB  - Inland lakes play important roles in water and greenhouse gas cycling in the
      environment. This study aims to test the performance of a flux-gradient system
      for simultaneous measurement of the fluxes of water vapor, CO2, and CH4 at a lake
      air interface. The concentration gradients over the water surface were measured
      with an analyzer based on the wavelength-scanned cavity ring-down spectroscopy
      technology, and the eddy diffusivity was measured with a sonic anemometer.
      Results of a zero-gradient test indicate a flux measurement precision of 4.8 W m(
      2) for water vapor, 0.010 mg m(-2) s(-1) for CO2, and 0.029 MUg m(-2) s(-1) for
      CH4. During the 620 day measurement period, 97%, 69%, and 67% of H2O, CO2, and
      CH4 hourly fluxes were higher in magnitude than the measurement precision, which
      confirms that the flux-gradient system had adequate precision for the measurement
      of the lake-air exchanges. This study illustrates four strengths of the flux
      gradient method: (1) the ability to simultaneously measure the flux of H2O, CO2,
      and CH4; (2) negligibly small density corrections; (3) the ability to resolve
      small CH4 gradient and flux; and (4) continuous and noninvasive operation. The
      annual mean CH4 flux (1.8 g CH4 m(-2) year(-1)) at this hypereutrophic lake was
      close to the median value for inland lakes in the world (1.6 g CH4 m(-2) year(
      1)). The system has adequate precision for CH4 flux for broad applications but
      requires further improvement to resolve small CO2 flux in many lakes. 

PMID- 25377991
TI  - A flexible sulfur-graphene-polypropylene separator integrated electrode for
      advanced Li-S batteries.
AB  - A flexible Li-S battery based on an integrated structure of sulfur and graphene
      on a separator is developed. The internal graphene current collector offers a
      continuous conductive pathway, a modified interface with sulfur, and a good
      barrier to and an effective reservoir for dissolved polysulfides, consequently
      improving the capacity and cyclic life of the Li-S battery. 

PMID- 25377989
TI  - Caveolins in cardioprotection - translatability and mechanisms.
AB  - Translation of preclinical treatments for ischaemia-reperfusion injury into
      clinical therapies has been limited by a number of factors. This review will
      focus on a single mode of cardiac protection related to a membrane scaffolding
      protein, caveolin, which regulates protective signalling as well as myocyte
      ultrastructure in the setting of ischaemic stress. Factors that have limited the
      clinical translation of protection will be considered specifically in terms of
      signalling and structural defects. The potential of caveolin to overcome barriers
      to protection with the ultimate hope of clinical translation will be discussed.

PMID- 25377993
TI  - Baccalaureate nursing students' perceptions of learning and supervision in the
      clinical environment.
AB  - This study is an exploration of nursing students' experiences within the clinical
      learning environment (CLE) and supervision provided in hospital settings. A total
      of 357 second-year nurse students from all universities in Cyprus participated in
      the study. Data were collected using the Clinical Learning Environment,
      Supervision and Nurse Teacher instrument. The dimension "supervisory relationship
      (mentor)", as well as the frequency of individualized supervision meetings, were
      found to be important variables in the students' clinical learning. However, no
      statistically-significant connection was established between successful mentor
      relationship and team supervision. The majority of students valued their mentor's
      supervision more highly than a nurse teacher's supervision toward the fulfillment
      of learning outcomes. The dimensions "premises of nursing care" and "premises of
      learning" were highly correlated, indicating that a key component of a quality
      clinical learning environment is the quality of care delivered. The results
      suggest the need to modify educational strategies that foster desirable learning
      for students in response to workplace demands. 

PMID- 25377992
TI  - Efficient synthesis of polypeptide-alpha-thioester by the method combining
      polypeptide expression and chemical activation for the semi-synthesis of
      interferon-gamma having oligosaccharides.
AB  - In order to synthesize interferon-gamma glycoform having an oligosaccharide at
      the 97 position by a semi-synthetic method, interferon-gamma-polypeptide-(1-94)
      alpha-hydrazide was prepared by the specific Cys-cyanylation of polypeptide-(1
      94)-Cys-His6 expressed from E. coli and subsequent hydrazinolysis in 22% yield
      (two steps). This polypeptide-alpha-hydrazide was then converted into
      corresponding polypeptide-alpha-thioester under NaNO2 /acid conditions followed
      by thiolysis in 83% yield.

PMID- 25377994
TI  - Conjugation of monocarboxybetaine molecules on amino-poly-p-xylylene films to
      reduce protein adsorption and cell adhesion.
AB  - A surface that resists protein adsorption and cell adhesion is highly desirable
      for many biomedical applications such as blood-contact devices and biosensors. In
      this study, we fabricated a carboxybetaine-containing surface and evaluated its
      antifouling efficacy. First, an amine-containing substrate was created by
      chemical vapor deposition of 4-aminomethyl-p-xylylene-co-p-xylylene (Amino-PPX).
      Aldehyde-ended carboxybetaine molecules were synthesized and conjugated onto
      Amino-PPX. The carboxybetaine-PPX surface greatly reduced protein adsorption and
      cell adhesion. The attachment of L929 cells on the carboxybetaine-PPX surface was
      reduced by 87% compared to the cell adhesion on Amino-PPX. Furthermore, RGD
      peptides could be conjugated on carboxybetaine-PPX to mediate specific cell
      adhesion. In conclusion, we demonstrate that a surface decoration with
      monocarboxybetaine molecules is useful for antifouling applications. 

PMID- 25377995
TI  - Differences in immunoreactive trypsin values between type of feeding and
      ethnicity in neonatal cystic fibrosis screening: a cross-sectional study.
AB  - BACKGROUND: We studied the differences in immunoreactive trypsin (IRT) in
      neonatal screening for cystic fibrosis (CF) associated individually with the age
      of the newborn, ethnicity and environmental temperature. In this study, we
      determine the overall influence of environmental temperature at birth, gender,
      feeding, gestational age, maternal age and ethnic origin on an abnormal IRT
      result. METHODS: Cross-sectional observational study. A sample was selected of
      newborns from Alicante (Spain) who underwent neonatal CF screening in 2012-2013.
      Primary variable: abnormal IRT levels (>=65 ng/ml). Secondary variables: gender,
      maternal origin, maternal age (years) (<20, 20-40, >40), gestational age (weeks)
      (<32, 32-37, >37), type of feeding (natural, formula, mixed and special
      nutrition), >20 days from birth to blood collection, and average temperature
      during the month of birth (in degrees C). Using a multivariate logistic
      regression model the adjusted odds ratios (ORs) were estimated to analyze the
      association between atypical IRT levels and the study variables. The alpha error
      was 5% and confidence intervals (CI) were calculated for the most relevant
      parameters. RESULTS: Of a total of 13,310 samples, 199 were abnormal (1.34%).
      Significant associated factors: feeding method (natural -> OR = 1; mixed -> OR =
      0.53, 95% CI: 0.31-0.89; formula -> OR = 0.72, 95% CI: 0.48-1.07; special -> OR =
      21.88, 95% CI: 6.92-69.14; p < 0.001). CONCLUSIONS: Newborns receiving special
      nutrition have a 20-fold higher risk for abnormal IRT levels, and screening is
      advisable once normalized feeding is initiated. It is advisable to consider
      ethnic variability. Seasonality was not important.

PMID- 25377996
TI  - Isolation of functionalized phenolic monomers through selective oxidation and C-O
      bond cleavage of the beta-O-4 linkages in lignin.
AB  - Functionalized phenolic monomers have been generated and isolated from an
      organosolv lignin through a two-step depolymerization process. Chemoselective
      catalytic oxidation of beta-O-4 linkages promoted by the DDQ/tBuONO/O2 system was
      achieved in model compounds, including polymeric models and in real lignin. The
      oxidized beta-O-4 linkages were then cleaved on reaction with zinc. Compared to
      many existing methods, this protocol, which can be achieved in one pot, is highly
      selective, giving rise to a simple mixture of products that can be readily
      purified to give pure compounds. The functionality present in these products
      makes them potentially valuable building blocks. 

PMID- 25377997
TI  - Influence of glutamic acid enantiomers on C-mineralization.
AB  - Seasonal dynamics in the mineralization of glutamic acid enantiomers in soils
      from selected ecosystems was determined and subjected to a range of treatments:
      ambient x elevated CO2 level and meadow x dense x thinned forest environment.
      Mineralization of glutamic acid was determined by incubation of the soil with 2
      mg L- or D-glutamic acid g(-1) of dry soil to induce the maximum respiration
      rate. Mineralization of glutamic acid enantiomers in soils fluctuates over the
      course of a vegetation season, following a similar trend across a range of
      ecosystems. Mineralization is affected by environmental changes and management
      practices, including elevated CO2 level and thinning intensity. L-glutamic acid
      metabolism is more dependent on soil type as compared to metabolism of its D
      enantiomer. The results support the hypothesis that the slower rate of D-
      compared to L- amino acid mineralization is due to different roles in anabolism
      and catabolism of the soil microbial community.

PMID- 25377998
TI  - Long-term outcome in children with infantile spasms treated with vigabatrin: a
      cohort of 180 patients.
AB  - OBJECTIVE: Evaluation of efficacy of vigabatrin as the first drug in infants with
      previously untreated infantile spasms (IS) and reporting the long-term outcome.
      METHODS: We analyzed a cohort of 180 infants with infantile spasms treated with
      vigabatrin as the first drug. Following initial evaluation and a 48-h basal
      period for counting the spasms, vigabatrin was administered using the same
      protocol in all. After 14 days all infants were assessed for therapeutic response
      (primary outcome). Psychomotor development was evaluated by a psychologist and
      neurologist prior to the initiation of treatment and during the follow-up.
      Seizure outcomes were followed prospectively, by seizure types and epilepsy
      syndromes. Long-term (secondary) outcomes included neurologic status, occurrence
      of late epilepsy, and developmental/cognitive status. RESULTS: Vigabatrin
      terminated the spasms in 101 patients (56.9%) at a mean period of 5 days.
      Patients with normal psychomotor development prior to the onset of spasms
      responded best. After follow-up of 2.4 to 18.9 years (mean 10.64; standard
      deviation [SD] 4.40), 38.1% of responders, treated with vigabatrin, had severe
      neurologic dysfunction, 42% had epilepsy, and 42.2% had unfavorable intellectual
      outcome. The group with symptomatic etiology and abnormal neurologic status at
      presentation demonstrated a significantly worse prognosis and a more unfavorable
      outcome than cryptogenic or idiopathic cases (85.1% and 81.6% versus 14.9% and 0%
      p = 0.001). Idiopathic patients treated with vigabatrin were all intellectually
      normal, except the youngest patient who had borderline cognitive function.
      SIGNIFICANCE: The most important prognostic factors were the underlying etiology
      and preexisting developmental profile. Long-term outcome in the patients treated
      with vigabatrin was similar to the outcome in patients treated with
      adrenocorticotropic hormone (ACTH) or corticosteroids, as reported in earlier
      studies. The long-term prognosis of idiopathic cases treated with vigabatrin was
      favorable.

PMID- 25377999
TI  - Left atrium dilatation and multiple vascular territory strokes.
AB  - BACKGROUND: Atrial fibrillation (AF) is a cause of ischemic stroke and is
      associated with recurrence and with acute multi-vessel territory non lacunar
      stroke. Many cryptogenic strokes could be secondary to undiagnosed paroxystic AF.
      As left atrium (LA) dilatation is a risk factor of AF, we sought to determine if
      moderate or severe LA dilatation was associated with multiple vascular territory
      infarcts on magnetic resonance imaging (MRI) in patients with acute ischemic
      stroke without known AF. Normal LA diameter values are <=4.0 cm for men and <=3.8
      for women. METHODS: Patients who presented at our center between 2006 and 2011
      with a diagnosis of acute ischemic stroke (AIS) or transient ischemick attack
      (TIA) who had a transthoracic echocardiography and a brain MRI were included.
      Patients with known or de novo AF diagnosed within 3 months of the event were
      excluded. The main outcome was the presence of acute multi-vessel territory
      infarct(s) on MRI. RESULTS: 356 patients were included. The mean LA diameter was
      37 mm in the control group (normal or mildly dilated LA) and 49 mm in those with
      moderately to severely enlarged LA (p<0.001). More patients in the LA dilatation
      group met the main outcome (20% vs 6%; OR 3.89; 95% CI 1.32-11.43; p=0.0014).
      CONCLUSIONS: LA dilatation (at least moderate) is associated with acute non
      lacunar multiple vascular territory infarcts on MRI in patients with AIS or TIA
      without known AF or a confirmed diagnosis of AF. Further studies are necessary to
      determine if this population might benefit from anticoagulation therapy.

PMID- 25378000
TI  - [Evaluation of a program for management of metabolic syndrome in adults with
      overweight and obesity].
AB  - BACKGROUND: The Chilean Ministry of Health developed a healthy lifestyles
      intervention directed to adults with overweight and cardiovascular risk factors,
      called "Program on Healthy Eating and Physical Activity" (PASAF). AIM: To
      evaluate the impact of PASAF on nutritional status and metabolic parameters.
      PATIENTS AND METHODS: We analyzed databases from three primary care centers
      belonging to a municipality of Metropolitan Santiago. We selected adults enrolled
      in the PASAF during three years (2007-2009). The program lasted four months and
      included an assessment of anthropometric and metabolic parameters at baseline and
      at the end, eight workshops with a nutritionist, seven with a psychologist and 32
      sessions of physical activity. RESULT: We evaluated 526 subjects aged >=18 years
      (93% females), of whom 85.6% attended the last appointment for assessment.
      Analyzing available data, attendance to workshops was <50% of the scheduled
      sessions. Weight, body mass index and waist circumference decreased significantly
      (median: -1.4 kg, -0.6 kg/m2 and -3 cm, respectively). The median weight loss was
      1.8% of initial weight and 17.1% of participants experienced a decrease >=5% of
      their initial weight. There were significant improvements in lipid levels and
      blood pressure among participants with lower initial excess weight. A reduction
      in fasting blood glucose was observed only among subjects who lost >=5% of their
      initial weight. CONCLUSIONS: The PASAF modestly reduced nutritional parameters.
      Correction of metabolic parameters was especially effective in less obese
      subjects. The attendance to workshops was low.

PMID- 25378001
TI  - [Development and validation of a clinical predictive model for delirium in
      hospitalized older people].
AB  - BACKGROUND: Delirium is a prevalent problem among older patients and it is
      frequently underdiagnosed. AIM: To develop and validate a clinical predictive
      model to identify patients at high risk of delirium. MATERIAL AND METHODS: Two
      consecutive prospective cohort studies were used to develop and validate the
      model. The development cohort included 542 consecutive medical inpatients, 65
      years or older. The validation cohort included 85 comparable patients. A
      predictive score was constructed with a multivariate analysis, using variables
      independently associated with delirium and subsequently tested in the new cohort.
      Patients were assessed within the first 48 hours of admission, and every 48 hours
      thereafter, using the Confusion Assessment Method to diagnose delirium,
      evaluating also the severity of underlying disease, comorbidities, functionality,
      and laboratory data. RESULTS: Delirium occurred in 192 patients (35.4%) of the
      development cohort and was independently associated with age and functional
      status assessed using the Barthel Index. With these two variables, the predictive
      score for delirium was developed and tested rendering an area under the receiver
      operating characteristic (ROC) of 0.80 (confidence intervals 0.77-0.85). Cut-off
      points were chosen to establish low, intermediate, and high-risk groups for
      delirium. According to these cut-off points, delirium frequencies in the
      development cohort were 8%, 23%, and 69%, and in the validation cohort 5%, 34%,
      and 66%, respectively (c2 p<0.05). CONCLUSIONS: This simple predictive model
      based on age and functional status may be a useful tool for identifying older
      patients risking delirium.

PMID- 25378002
TI  - [Feeding habits and lifestyles of male construction workers].
AB  - BACKGROUND: The less affluent and educated members of the society tend to be less
      prone to healthy lifestyles. AIM: To describe feeding habits, nutrition, quality
      of life and working conditions of construction workers comparing two recent
      surveys, namely the 2009 Chilean National Health Survey (NHS) and the 2010 Work,
      Employment and Health Survey (WEH). MATERIAL AND METHODS: One hundred ninety male
      workers aged 43+/-13 years were surveyed about feeding habits during working days
      and weekends, smoking and usual physical activity. Weight, height and blood
      pressure were also measured. RESULTS: In 2010, 82% of workers were overweight or
      obese compared with 67% rates in the NHS of 2009. The rate of sedentariness was
      86% compared with 84% in the NHS of 2009 and 93% in the WEH 2010. Forty one
      percent smoked and those aged less than 25 years consumed more calories than the
      other age groups. There was a high intake of carbonated beverages, bread, salted
      and red meats and a low consumption of fruits, vegetables, legumes and fish.
      Seventy seven percent had a meal at midafternoon and only 25% ate supper. Lunch
      had a fixed schedule, was considered good and usually was prepared by a family
      member. The level of satisfaction with work, family life and life in general was
      high. The satisfaction with health and physical condition was lower. CONCLUSIONS:
      The unhealthy lifestyles of these construction workers should alert health
      authorities.

PMID- 25378003
TI  - [Levels of glycosylated hemoglobin and the difference in the cost of health care
      for diabetic patients: an econometric study].
AB  - BACKGROUND: Complications increase treatment costs of diabetes mellitus (DM). An
      adequate metabolic control of the disease could reduce these costs. AIM: To
      evaluate the costs of medical care for a cohort of patients with DM, according to
      their degree of metabolic compensation. MATERIAL AND METHODS: All diabetic
      patients attended in a regional hospital from 2005 to 2010 were analyzed. A
      correlational study between costs of individual healthcare and levels of
      glycosylated hemoglobin (HbA1c), was performed in a series of annual cross
      sectional measurements. RESULTS: The study comprised 1,644 diabetic patients.
      During the study period the average cost of healthcare per patient increased from
      $878,000 to more than $1,000,000 Chilean pesos (CLP) during the study period. The
      percentage of patients with HbA1c levels below 7.0% varied between 43.0% and
      54.9%. Costs for patients with HbA1c levels between 7 and 8.9% were 1.3 to 1.5
      times greater. For the group of patients with HbA1c levels between 9 and 10.9%
      the costs increased 1.4 to 1.6 times. For patients with HbA1c levels greater than
      11.0%, healthcare costs doubled. CONCLUSIONS: Healthcare expenditure varied
      according to metabolic control, which is consistent with international findings.
      This study was limited by its selected population, incomplete information on
      health expenditures, and the inclusion of only direct costs to the health system.
      If all patients would achieve metabolic compensation, the yearly savings would be
      CLP $308,000,000 (or USD $657,000).

PMID- 25378004
TI  - [Household availability of ready-to-consume food and drink products in Chile:
      impact on nutritional quality of the diet].
AB  - BACKGROUND: Processed foodstuff may have a lower nutritional value than natural
      products. AIM: To analyze the impact of ready-to-consume products on diet quality
      of Chilean households. MATERIAL AND METHODS: A national representative sample of
      10,096 households, based on the 6th Survey on Household Budget and Expenses (VI
      Encuesta de Presupuestos y Gastos Familiares, 2006-2007), was studied. Foodstuffs
      were classified as follows: 1) Unprocessed foods or minimally processed foods
      (G1); 2) Processed culinary ingredients (G2); and 3) Ready-to-consume products
      (G3). Calorie contribution and energy availability of each household food group,
      was calculated. The nutritional profile of the national food basket was
      calculated and compared with two simulated baskets (G3 vs G1+G2), based on
      international nutritional recommendations. RESULTS: Overall energy availability
      was of 1,885 kcal per capita/ day; 24% derived from unprocessed foods (G1), 21%
      from processed culinary ingredients (G2) and 55% from ready-to-consume products
      (G3), whose proportion increased along with income level. The 2007 national food
      basket contained an excess of total fat (34% vs 30%), free sugars (16% vs 10%),
      energy density (2.1 vs 1.3 kcal/gram) and a low amount of fiber (8.4 vs 12.5
      g/1,000 kcal). The basket consisting in ready-to-consume products (G3) had a
      higher percentage of carbohydrates (61% vs 46%) than the basket consisting in
      unprocessed foods and ingredients (G1+G2). It also had a higher percentage of
      free sugars (17% vs 15%), less dietary fiber (7 vs. 10 g/1,000 kcal) and, above
      all, a higher energy density (2.6 vs 1.6 kcal/g). CONCLUSIONS: The Chilean
      dietary pattern, based on ready-to-consume products (G3), is affecting the
      nutritional quality of the diet.

PMID- 25378005
TI  - [Cutaneous manifestations detected in human T cell lymphotropic virus type 1
      infected Chilean blood donors].
AB  - BACKGROUND: Most human T cell lymphotropic virus type 1 (HTLV-1) infected
      individuals are asymptomatic, but they commonly present cutaneous lesions that
      could be considered warning signs of the disease. AIM: To identify the main
      cutaneous manifestations present in HTLV-1 infected blood donors and compare them
      with healthy donors. MATERIALS AND METHODS: Two blood donor groups from the blood
      bank of an emergency hospital were matched according to gender and age. One group
      was formed by HTLV-1 (+) (cases) and the other by HTLV-1 (-) donors (controls). A
      blind examiner to the serologic condition, evaluated their cutaneous
      manifestations. RESULTS: Twenty five cases and 25 controls aged 18 to 60 years
      (24 females) were evaluated. One or more cutaneous manifestations were found in
      24 (96%) cases and in 15 (60%) controls (p<0.01). Inflammatory cutaneous diseases
      were found in 19 (76%) cases and in 9 (36%) controls (p<0.01). Dermatophytosis
      was found in 18 (72%) cases and in 12 (48%) controls (NS). CONCLUSIONS: HTLV-1
      infected Chilean subjects have a higher frequency of dermatoses than their
      healthy counterparts.

PMID- 25378006
TI  - [Overlapping features of frontotemporal dementia and amyotrophic lateral
      sclerosis].
AB  - Recent genetic and neuropathologic advances support the concept that
      frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are
      overlapping multisystem disorders. While 10-15% of ALS patients fulfil criteria
      for FTD, features of motor neuron disease appear in approximately 15% of FTD
      patients, during the evolution of the disease. This overlap has been reinforced
      by the discovery of Transactive Response DNA Binding Protein 43 kDa (TDP43)
      inclusions as the main neuropathologic finding in the majority of ALS cases and
      almost a half of FTD cases. Also, an expansion in the intron of C9ORF72
      (chromosome 9p21) has been identified in families affected by ALS, ALS-FTD and
      FTD. This review provides an update on the recent genetic and neuropathologic
      findings of ALS and FTD and a characterization of their clinical presentation
      forms, based on the current diagnostic criteria. Finally it underscores the
      importance of having a national registry of patients with ALS and FTD, to provide
      an earlier diagnosis and a multidisciplinary care. 

PMID- 25378007
TI  - [New lipid lowering agents].
AB  - Statins are the preferred treatment for hypercholesterolemia and several studies
      have demonstrated their long-term safety and efficacy in reducing cardiovascular
      morbidity and mortality. However, in some cases of severe hypercholesterolemia
      such as homozygous and heterozygous familial hypercholesterolemia or statin
      intolerant patients, statins can be less efficient. In recent years, new lipid
      lowering agents with novel mechanisms of action have been developed to reduce LDL
      cholesterol in patients with severe hypercholesterolemia, associated or not to
      conventional lipid-lowering therapy. These therapies include microsomal transfer
      protein inhibitor (Lomitapide), antisense oligonucleotide to Apo B100
      (Mipomersen) and monoclonal antibodies against Proprotein convertase
      subtilisin/kexin type 9 (PCSK9). Different studies have shown the great
      effectiveness of these new therapies. Short-term studies confirmed their adequate
      security profile, especially in patients with homozygous familiar
      hypercholesterolemia or severe hypercholesterolemia. Some of these agents have
      been also tested in statin-intolerant patients. However, long-term studies are
      needed to evaluate their safety, effectiveness and impact on cardiovascular risk
      reduction. 

PMID- 25378008
TI  - [Experience of a research Ethics Committee and the challenges of the new Chilean
      legislation on research in human beings].
AB  - The welfare of research participants must be guaranteed by international ethical
      standards. This article communicates the procedures of the Research Ethics
      Committee of the School of Medicine, University of Chile (CEISH). The new Chilean
      legislation on research in human beings is also discussed. Law 20.120: "On
      scientific research in human beings, its genome and forbidding human cloning"
      establishes the ethical principles that must be accomplished in every research
      involving human beings. Article 28 of the Law 20.584 "Regulation of the rights
      and duties of health care users", forbids the participation of handicapped people
      who cannot express their will in scientific research. Article 13 states that
      people not related directly with patient care cannot have access to his clinical
      records (with the exception of people with notarial authorization by the
      patient). CEISH proposes that, in case of people with intellectual deficiency,
      the decision to approve a scientific research should be analyzed on an individual
      basis. If the person is capable of expressing his or her will or has stated his
      or her consent beforehand, the research can be authorized. If the person cannot
      express his or her will, the scientific research cannot take place. In
      prospective studies, a consent from the patient and an authorization of the
      health authority should be required to access clinical records. In retrospective
      studies, consent should be obtained from the patient when personal information is
      going to be used. If the information is nameless, the consent can be disregarded.

PMID- 25378009
TI  - [Medical and ethical basis for embryo cryopreservation].
AB  - As part of Assisted Reproductive Technologies (ART), the advent of embryo
      freezing lowered the number of embryos transferred, decreasing multiple births
      without jeopardizing pregnancy rates. Using vitrification technology, 90% of
      embryos survive after thawing, producing clinical pregnancy rates similar to
      those of fresh embryos (41.6%y 44.3% respectively). Furthermore, cumulative
      pregnancy rates, obtained after transferring fresh plus frozen/thawed embryos,
      can reach 70%. Frozen embryo transfers (FET) are reported by six of seven
      institutions, which are part of the Chilean ART registry, and altogether
      constitute 22.8% of all ART procedures. Increasing use of cryopreservation
      lowered overall multiple gestations from 33% in 1995 to 23% in 2011, reducing pre
      term births and perinatal mortality. For many people, embryo freezing generates
      ethical dilemmas, due to the potential risks to which embryos are exposed, and
      the uncontrolled accumulation and disposal of human embryos. Scientific evidence
      today shows that frozen/thawed embryos are not exposed to disproportionate risks,
      and by hindering its use, both women and their children are exposed to the risks
      of multiple gestation, repeated cycles of ovarian hormonal stimulation or the
      impossibility to afford repeated ART cycles. In this article, we provide
      biomedical, as well as ethical, arguments to sustain that embryo cryopreservation
      is not only justified but fundamental when offering infertility treatment with
      ART. 

PMID- 25378010
TI  - [Medical, ethical and legal issues in cryopreservation of human embryos].
AB  - Embryo cryopreservation improves efficiency and security of assisted reproduction
      techniques. Nonetheless, it can be questionable, so it must be justified from
      technical, legal and ethical points of view. This article analyses these
      perspectives. Embryo cryopreservation maximizes the probability of pregnancy,
      avoids new ovary stimulations and reduces the occurrence of multiple gestations.
      There is consensus that the in vitro embryo deserves legal protection by its own,
      although not as a newborn. Very few countries prohibit embryo cryopreservation
      based on the legal duty to protect human life since fecundation. Those countries
      that allow it, privilege women's reproductive rights. In Chile and in Latin
      America, no laws have been promulgated to regulate human assisted reproduction.
      The moral status of the embryo depends on how it is considered. Some believe it
      is a potential person while others think it is just a group of cells, but all
      recognize that it requires some kind of respect and protection. There is lack of
      information about the number of frozen embryos and their final destination. As a
      conclusion the authors propose that women or couples should have the right to
      decide autonomously, while institutions ought to be clear in their regulations.
      And the legislation must establish the legal status of the embryo before its
      implantation, the couples' rights and the regulation of the embryo
      cryopreservation. Personal, institutional or legal decisions must assume a
      concept about the moral status of the human embryo and try to avoid their
      destruction or indefinite storage.

PMID- 25378012
TI  - [Left ventricular assistant devices for end-stage heart failure: report of two
      cases].
AB  - In the last 2 decades, there have been significant advances in medical treatment
      of heart failure. However, there is a group of patients who are refractory to the
      available medical therapy and progress inevitably to a state of end-stage heart
      failure, whose only therapeutic alternative is cardiac transplantation. But this
      is an option limited by the scarce availability of donors. Therefore many
      patients die waiting for an organ. Recently, extra or intracorporeal left
      ventricular devices have emerged as a viable alternative for patients with end
      stage heart failure waiting for a heart transplant. These devices discharge the
      left ventricle, increasing cardiac output and improving systemic perfusion. This
      year, in our hospital we began a left ventricular device implantation program for
      the most severely ill patients on the waiting list for cardiac transplantation.
      We report two males aged 30 and 53 years, in whom a left ventricular device was
      successfully implanted, using a minimally invasive surgical technique developed
      at the University of Hannover in Germany. 

PMID- 25378013
TI  - Brown tumors of the femur and pelvis secondary to a parathyroid carcinoma: report
      of one case.
AB  - Brown tumors result from excess osteoclast activity and consist of collections of
      osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone.
      They are secondary to hyperparathyroidism (HPT). Their incidence is higher in
      primary than in secondary hyperparathyroidism. We report a 69 years-old male,
      admitted in a state of confusion, lethargy and bedridden, with a pathological
      fracture of the femur caused by a brown tumor. The laboratory examination
      revealed a hypercalcemia (8.85 mEq/L), with high levels of ionized Ca (5.48
      mEq/L), serum alkaline phosphatases (416 U/L) and serum parathormone (120 pg/mL).
      Ultrasound examination of the neck showed a large parathyroid tumor, probably
      corresponding to a carcinoma. A primary HPT was diagnosed. The patient was
      hydrated and high doses of diuretics and bisphosphonates were administered. After
      correction of serum calcium and neurologic symptoms, the patient was operated,
      performing an extensive resection of the tumor. The pathology report confirmed
      the diagnosis of parathyroid carcinoma.

PMID- 25378014
TI  - [Aortitis: report of three cases].
AB  - Aortitis is a nonspecific term that describes an inflammation of the aortic wall
      caused by inflammatory, infectious, paraneoplastic and idiopathic diseases. The
      symptoms are variable and nonspecific; therefore a high level of clinical
      suspicion is required to diagnose it. It is often an incidental finding while
      looking for other diagnoses and it is confirmed mainly through imaging studies.
      We report three cases of aortitis: A 29-year-old woman presenting with alopecia,
      oral and nasal ulcers and positive antinuclear antibodies. A CAT scan showed a
      segmental thickening of thoracic aorta, with dilated and stenotic areas. She was
      successfully treated with steroids, hydroxychloroquine, cyclophosphamide and
      azathioprine. A 41-year-old male presenting with dorsal pain and cough. The CAT
      scan showed an extra-intimal thickening of the descending aorta and stenosis of
      the celiac artery. The final diagnosis was a polyangiitis and was treated with
      steroids, cyclophosphamide and azathioprine. A 28-year-old woman presenting with
      pain in the left upper abdomen. Imaging studies showed a thickening of the aortic
      arch and subclavian artery. The final diagnosis was sarcoidosis and the patient
      was treated with prednisone. 

PMID- 25378015
TI  - [Landry, Kussmaul, and Guillain-Barre-Strohl syndrome].

PMID- 25378016
TI  - [Gastroduodenal cryptococcosis in an AIDS patient].

PMID- 25378017
TI  - [Incorporation of psychological first aid to the undergraduate curriculum].

PMID- 25378018
TI  - [Focused assessment of quality of life in adults].

PMID- 25378019
TI  - [Appendicitis and its history].

PMID- 25378020
TI  - An extremely low-density human population exterminated New Zealand moa.
AB  - New Zealand moa (Aves: Dinornithiformes) are the only late Quaternary megafauna
      whose extinction was clearly caused by humans. New Zealand offers the best
      opportunity to estimate the number of people involved in a megafaunal extinction
      event because, uniquely, both the Polynesian settlement of New Zealand and moa
      extinction are recent enough to be dated with a high degree of precision. In
      addition, the founding human population can be estimated from genetic evidence.
      Here we show that the Polynesian population of New Zealand would not have
      exceeded 2,000 individuals before extinction of moa populations in the habitable
      areas of the eastern South Island. During a brief (<150 years) period and at
      population densities that never exceeded ~0.01 km(-2), Polynesians exterminated
      viable populations of moa by hunting and removal of habitat. High human
      population densities are not required in models of megafaunal extinction. 

PMID- 25378021
TI  - Characteristic differences and reference ranges for mitral, tricuspid, aortic,
      and pulmonary Doppler velocity waveforms during fetal life.
AB  - OBJECTIVES: We aimed to construct reference ranges for time intervals of each
      component of cardiac flow velocity waveforms in normal fetuses, comparing those
      variables between right and left ventricles. METHODS: In 359 fetuses at the
      gestational age of 17-38 weeks, the durations of atrioventricular (AV) valve
      opening (AVVO), AV valve closure (AVVC), total E- (total-E) and A- (total-A)
      waves, total ejection time (total-ET), acceleration time (acc-E for E-wave, acc-A
      for A-wave, and acc-ET for ejection time), and deceleration time (dec-E for E
      wave, dec-A for A-wave, and dec-ET for ejection time) were studied cross
      sectionally. RESULTS: Both right and left acc-E showed the strongest correlations
      with gestational age (r = 0.478 and r = 0.519, respectively). Left AVVO showed a
      stronger correlation (r = 0.474) than right AVVO (r = 0.282) and, conversely,
      right AVVC showed a stronger correlation (r = 0.399) than left AVVC (r = 0.195)
      with gestational age. Significant differences (all P values <0.001) were observed
      for all right and left parameters other than total-A and acc-E. CONCLUSIONS:
      Characteristic differences between right and left ventricles were found in the
      reference ranges, suggesting the developmental properties of the fetal heart. (c)
      2014 John Wiley & Sons, Ltd.

PMID- 25378024
TI  - Is emotional restraint a healthy response to adversity?

PMID- 25378022
TI  - Genome-wide cloning, identification, classification and functional analysis of
      cotton heat shock transcription factors in cotton (Gossypium hirsutum).
AB  - BACKGROUND: Heat shock transcriptional factors (Hsfs) play important roles in the
      processes of biotic and abiotic stresses as well as in plant development. Cotton
      (Gossypium hirsutum, 2n=4x=(AD)2=52) is an important crop for natural fiber
      production. Due to continuous high temperature and intermittent drought, heat
      stress is becoming a handicap to improve cotton yield and lint quality. Recently,
      the related wild diploid species Gossypium raimondii genome (2n=2x=(D5)2=26) has
      been fully sequenced. In order to analyze the functions of different Hsfs at the
      genome-wide level, detailed characterization and analysis of the Hsf gene family
      in G. hirsutum is indispensable. RESULTS: EST assembly and genome-wide analyses
      were applied to clone and identify heat shock transcription factor (Hsf) genes in
      Upland cotton (GhHsf). Forty GhHsf genes were cloned, identified and classified
      into three main classes (A, B and C) according to the characteristics of their
      domains. Analysis of gene duplications showed that GhHsfs have occurred more
      frequently than reported in plant genomes such as Arabidopsis and Populus.
      Quantitative real-time PCR (qRT-PCR) showed that all GhHsf transcripts are
      expressed in most cotton plant tissues including roots, stems, leaves and
      developing fibers, and abundantly in developing ovules. Three expression patterns
      were confirmed in GhHsfs when cotton plants were exposed to high temperature for
      1 h. GhHsf39 exhibited the most immediate response to heat shock. Comparative
      analysis of Hsfs expression differences between the wild-type and fiberless
      mutant suggested that Hsfs are involved in fiber development. CONCLUSIONS:
      Comparative genome analysis showed that Upland cotton D-subgenome contains 40 Hsf
      members, and that the whole genome of Upland cotton contains more than 80 Hsf
      genes due to genome duplication. The expression patterns in different tissues in
      response to heat shock showed that GhHsfs are important for heat stress as well
      as fiber development. These results provide an improved understanding of the
      roles of the Hsf gene family during stress responses and fiber development.

PMID- 25378023
TI  - Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal
      and non-fatal cardiovascular events: patient level meta-analysis.
AB  - OBJECTIVES: To examine the safety and effectiveness of cobalt-chromium everolimus
      eluting stents compared with bare metal stents. DESIGN: Individual patient data
      meta-analysis of randomised controlled trials. Cox proportional regression models
      stratified by trial, containing random effects, were used to assess the impact of
      stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes
      were reported. DATA SOURCES AND STUDY SELECTION: Medline, Embase, the Cochrane
      Central Register of Controlled Trials. Randomised controlled trials that compared
      cobalt-chromium everolimus eluting stents with bare metal stents were selected.
      The principal investigators whose trials met the inclusion criteria provided data
      for individual patients. PRIMARY OUTCOMES: The primary outcome was cardiac
      mortality. Secondary endpoints were myocardial infarction, definite stent
      thrombosis, definite or probable stent thrombosis, target vessel
      revascularisation, and all cause death. RESULTS: The search yielded five
      randomised controlled trials, comprising 4896 participants. Compared with
      patients receiving bare metal stents, participants receiving cobalt-chromium
      everolimus eluting stents had a significant reduction of cardiac mortality
      (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial
      infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to
      0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73;
      P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a
      median follow-up of 720 days. There was no significant difference in all cause
      death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at
      multivariable regression after adjustment for the acuity of clinical syndrome
      (for instance, acute coronary syndrome v stable coronary artery disease),
      diabetes mellitus, female sex, use of glycoprotein IIb/IIIa inhibitors, and up to
      one year v longer duration treatment with dual antiplatelets. CONCLUSIONS: This
      meta-analysis offers evidence that compared with bare metal stents the use of
      cobalt-chromium everolimus eluting stents improves global cardiovascular outcomes
      including cardiac survival, myocardial infarction, and overall stent thrombosis.

PMID- 25378025
TI  - MPs raise alarm over underfunded mental health services for children.

PMID- 25378026
TI  - Frequencies of myohistological mitochondrial changes in patients with
      mitochondrial DNA deletions and the common m.3243A>G point mutation.
AB  - Frequencies of typical myohistological changes such as ragged red fibers (RRF)
      and cytochrome c oxidase (COX)-deficient fibers have been suggested to be
      dependent on underlying mitochondrial DNA (mtDNA) defect. However, there are no
      systematic studies comparing frequencies of myohistological changes and
      underlying genotypes. The histopathological changes were analysed in 29 patients
      with genetically confirmed mitochondrial myopathies. Genotypes included multiple
      mtDNA deletions due to POLG1 mutations (n = 11), single mtDNA deletion (n = 10)
      and mtDNA point mutation m.3243A>G (n = 8). Histochemical reactions, including
      Gomori-trichome, COX/SDH (succinate dehydrogenase) and SDH as well as
      immunohistological reaction with COX-antibody against subunit I (COI) were
      carried out in muscle biopsy sections of all patients. The COX-deficient fibers
      were observed most frequently in all three patient groups. The frequencies of
      myopathological changes were not significantly different in the different
      genotypes in all three histochemical stains. However, there was a tendency to
      lower means and variations in patients with point mutation. Only COI-negative
      fibers were histochemically negative for COX activity in all patient groups.
      Frequency of COI-negative fibers was significantly lower in patients with mtDNA
      point mutation than in patients with deletions. This suggests that impact of
      point mutation on protein synthesis is less than that of deletions.

PMID- 25378027
TI  - A gene network bioinformatics analysis for pemphigoid autoimmune blistering
      diseases.
AB  - OBJECTIVE: In this theoretical study, a text mining search and clustering
      analysis of data related to genes potentially involved in human pemphigoid
      autoimmune blistering diseases (PAIBD) was performed using web tools to create a
      gene/protein interaction network. METHODS: The Search Tool for the Retrieval of
      Interacting Genes/Proteins (STRING) database was employed to identify a final set
      of PAIBD-involved genes and to calculate the overall significant interactions
      among genes: for each gene, the weighted number of links, or WNL, was registered
      and a clustering procedure was performed using the WNL analysis. Genes were
      ranked in class (leader, B, C, D and so on, up to orphans). An ontological
      analysis was performed for the set of 'leader' genes. RESULTS: Using the above
      mentioned data network, 115 genes represented the final set; leader genes
      numbered 7 (intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFNG),
      interleukin (IL)-2, IL-4, IL-6, IL-8 and tumour necrosis factor (TNF)), class B
      genes were 13, whereas the orphans were 24. The ontological analysis attested
      that the molecular action was focused on extracellular space and cell surface,
      whereas the activation and regulation of the immunity system was widely involved.
      CONCLUSIONS: Despite the limited knowledge of the present pathologic phenomenon,
      attested by the presence of 24 genes revealing no protein-protein direct or
      indirect interactions, the network showed significant pathways gathered in
      several subgroups: cellular components, molecular functions, biological processes
      and the pathologic phenomenon obtained from the Kyoto Encyclopaedia of Genes and
      Genomes (KEGG) database. CLINICAL RELEVANCE: The molecular basis for PAIBD was
      summarised and expanded, which will perhaps give researchers promising directions
      for the identification of new therapeutic targets.

PMID- 25378028
TI  - Can exhaled nitric oxide be a surrogate marker of bronchial hyperresponsiveness
      to adenosine 5'-monophosphate in steroid-naive asthmatic children?
AB  - BACKGROUND: The interrelation between airway inflammation, bronchial
      hyperresponsiveness (BHR) and atopy remains controversial. OBJECTIVE: The aim of
      this study was to document whether exhaled nitric oxide (eNO) may be used as a
      surrogate marker that predicts BHR to adenosine 5'-monophosphate (AMP) in steroid
      naive school children with asthma. METHODS: This study was a retrospective
      analysis of steroid-naive school age children with atopic and non-atopic asthma.
      All patients whose eNO levels had been measured and who had been challenged with
      both methacholine (MCH) and AMP were included. Receiver operation characteristic
      analysis was performed, in both the atopic and the non-atopic groups, to evaluate
      the ability of eNO to detect the BHR to AMP. RESULTS: One hundred and sixteen
      patients, sixty-nine (59.5%) of whom had been atopic, were included in the
      analysis. In the atopic group, eNO values were significantly higher in patients
      with BHR to AMP compared to those without BHR to AMP (51.9 +/- 16.9 p.p.b. vs.
      33.7 +/- 16.4 p.p.b.; P < 0.001), whereas in the non-atopic group, the
      differences were not statistically significant (29.7 +/- 16.9 p.p.b. vs. 22.6 +/-
      8.1 p.p.b.; P = 0.152). In the atopic group, eNO levels (R(2) : 0.401; beta:
      0.092; 95% CI: 1.19-14.42; OR: 7.12; P = 0.008) were found to be the only
      independent factor for BHR to AMP, whereas none of the parameters predicted BHR
      to AMP in the non-atopic group. The best cut-off value of eNO that significantly
      predicts BHR to AMP was 33.3 p.p.b. in the atopic group (P < 0.001), whereas a
      significant cut-off value for eNO that predicts BHR to AMP was not determined in
      the non-atopic group (P = 0.142). An eNO <= 17.4 p.p.b. has 100% negative
      predictive values and 100% sensitivity and 60.47% PPV for prediction of BHR to
      AMP in the atopic group. CONCLUSIONS: Exhaled NO may be used to predict BHR to
      AMP in atopic but not in non-atopic steroid-naive asthmatic children.

PMID- 25378029
TI  - Sorption and desorption of Cr(VI) ions from water by biochars in different
      environmental conditions.
AB  - In the present research, the potential of two biochars produced by the thermal
      decomposition of wheat straw (BCS) and wicker (BCW) for Cr(VI) ions removing from
      wastewater was investigated. The pH and the presence of chlorides and nitrates
      were also investigated. The Freundlich and Langmuir models were applied for the
      characterization of adsorption isotherms. The Langmuir model has better fitting
      of adsorption isotherms than the Freundlich model. The sorption process can be
      described by the pseudo second-order equation. The optimal adsorption capacities
      were obtained at pH 2 and were 24.6 and 23.6 mg/g for BCS and BCW, respectively.
      X-ray photoelectron spectroscopy (XPS) studies confirmed that Cr(III) ions were
      the most abundant chromium species on the biochars' surface. The results
      indicated that the sorption mechanism of Cr(VI) on biochar involves anionic and
      cationic adsorption combined with Cr(VI) species reduction.

PMID- 25378030
TI  - Potentially toxic element phytoavailability assessment in Technosols from former
      smelting and mining areas.
AB  - This study reports the chemical bioavailability of several potentially toxic
      elements (Zn, Pb, Cd, As, and Sb) in contaminated Technosols from two former
      smelting and mining areas. Though these elements have long been recognized as
      potentially harmful elements, understanding of their toxicity and environmental
      behavior in Technosols developed on former mining and smelting sites are more
      limited, particularly for As and Sb. Surface soils were sampled from metallophyte
      grassland contaminated with Zn, Pb, and Cd located at Mortagne-du-Nord (North
      France) and from a former mining settling basin contaminated with As, Pb, and Sb
      located at la Petite Faye (Limoges, France). Various selective single extraction
      procedures (CaCl2, NaNO3, NH4NO3, DTPA, and EDTA) were used together with
      germination tests with dwarf beans whose shoots were analyzed for their
      potentially toxic element concentrations after 21 days of growth. The extraction
      capacity of the potentially toxic elements followed the order EDTA > DTPA >
      NH4NO3 > CaCl2 > NaNO3 for both studied areas. Pearson's correlation coefficient
      analysis between the concentrations of potentially toxic elements accumulated in
      bean primary leaves or their mineral mass with their extractable concentrations
      showed a positive significant correlation with dilute CaCl2 and nitrate solutions
      extraction procedures. In contrast, for all studied elements, except Pb, the
      complexing and chelating extractants (EDTA and DTPA) exhibited poor correlation
      with the dwarf bean leaves concentrations. Moreover, results showed that the 0.01
      M CaCl2 extraction procedure was the most suitable and provided the most useful
      indications of metal phytoavailability for studied elements.

PMID- 25378031
TI  - Ecological risk assessment and sources of heavy metals in sediment from Daling
      River basin.
AB  - To investigate the distribution, source, and ecological risk of heavy metals in
      Daling River basin, 28 surface sediments collected in this region were analyzed
      by experimental and theoretical methods. Seven heavy metals, including Pb, Cr,
      Hg, Cu, As, Cd, and Zn, were detected in all samples. Monte Carlo simulation was
      used to assess the ecological risks of these heavy metals. It was found that the
      pollution of Cd was the most serious; the ecological risks in Daling River and
      Bohai Bay were significantly higher than those in estuary, Bohai Sea, and
      wetland, but overall, the ecological risks of these heavy metals were low to
      aquatic organisms in Daling River basin at present. Correlation analysis,
      principal component analysis, and cluster analysis showed that these heavy metals
      might originate from the same pollution sources located near Daling River and
      Bohai Bay. 

PMID- 25378032
TI  - Ecology, functioning and management of wetland systems.

PMID- 25378033
TI  - Cytogenotoxicity assessment of monocrotophos and butachlor at single and combined
      chronic exposures in the fish Catla catla (Hamilton).
AB  - Cytogenotoxic effects in the form of micronuclei and deformed nucleus, nuclear
      buds, binucleated cells, vacuolated nucleus, vacuolated cytoplasm, echinocytes,
      and enucleus induced by two compounds belonging to two different chemical classes
      of agrochemicals (monocrotophos and butachlor) at sublethal concentrations
      (0.625, 1.3, and 2.3 ppm and 0.016, 0.032, and 0.064 ppm) in single and combined
      chronic exposures were studied under laboratory conditions for a period of 35
      days in the economically important Indian fish Catla catla. Statistically
      significant duration-dependent increases in the frequencies of micronucleus (MN)
      and other cytological anomalies were observed. Compared to single exposures, a
      twofold increase in micronuclei frequency was noted at combined exposures
      indicating the synergistic phenomenon. Binucleated and enucleated cells appeared
      only in fishes exposed to sublethal concentrations of butachlor. The present
      study is the first of its kind in exploring a significant positive correlation
      between micronuclei and other nuclear anomalies suggesting them as new possible
      biomarkers of genotoxicity after agrochemical exposures. The study highlights the
      sensitivity of the assay in exploring various predictive biomarkers of genotoxic
      and cytotoxic events and also elicits the synergistic effects of agrochemicals in
      apparently healthy fishes. C. catla can be considered as a suitable aquatic
      biomonitoring sentinel species of contaminated water bodies. 

PMID- 25378034
TI  - Oral glucose solution to alleviate pain induced by intramuscular injections in
      preterm infants.
AB  - PURPOSE: The purpose was to assess the effectiveness of 5% oral glucose solution
      in reducing pain in preterm infants during intramuscular injection. DESIGN AND
      METHODS: We conducted a prospective, randomized, controlled, unblinded trial to
      investigate the effect of glucose solution on the pain of intramuscular injection
      in preterm infants (N = 80). RESULTS: Infants who received oral glucose had
      significantly lower pain scores (p < .001), less crying time (p < .001), higher
      oxygen saturation (p < .001), and lower heart rate after compared with during the
      procedure (p = .02). PRACTICE IMPLICATIONS: Our results suggest that oral
      glucose, even if used in the lowest dose, may have a pain-relieving effect in
      preterm infants if administered pre-procedure.

PMID- 25378035
TI  - Catheter-tissue contact force values do not impact mid-term clinical outcome
      following pulmonary vein isolation in patients with paroxysmal atrial
      fibrillation.
AB  - PURPOSE: Catheter-tissue contact is critical for effective lesion creation in
      radiofrequency catheter ablation (RFCA). In a multicenter prospective study, we
      assessed the relationship between catheter contact force (CF) during RFCA for
      paroxysmal atrial fibrillation (AF) and clinical recurrences over a mid-term
      follow-up. METHODS: All patients underwent RFCA for paroxysmal AF by antral
      pulmonary vein (PV) isolation, aiming at entry and exit conduction block in all
      PVs. A new open-irrigated tip catheter with CF sensing (SmartTouch(TM), Biosense
      Webster Inc. CA) was used. All patients were followed for at least 12 months and
      the relationship between CF and clinical outcomes assessed. RESULTS: One year
      follow-up was available in 92/95 of the patients enrolled. Acute PV isolation was
      achieved in 100 % of the veins. Mean CF during RFCA was 12.2 +/- 3.9 g. Mean
      force-time integral (FTI) was 733 +/- 505 gs. Following the 3-month blanking
      period, 17 (18 %) patients experienced at least 1 atrial tachyarrhythmia relapse.
      There was no statistical difference in mean CF (13 +/- 3.4 g vs 12 +/- 4 g, p =
      0.32) and mean FTI (713 +/- 487 gs vs 822 +/- 590 gs, p = 0.42) between patients
      with and without arrhythmia recurrences. Recurrences were recorded in 22 % of
      patients achieving a mean FTI value below the median of 544 gs and in 15 % of
      patients with a mean FTI value above the median (p = 0.64). CONCLUSIONS: RFCA
      with CF data during PV isolation for paroxysmal AF improves physician's knowledge
      on catheter-tissue contact. In the present dataset, however, higher CF values did
      not impact mid-term clinical RFCA outcome.

PMID- 25378036
TI  - Visual impairment and hip fractures: a case-control study in elderly patients.
AB  - AIMS: To investigate the relationship between visual impairment and fall-related
      hip fracture and to determine the etiology of visual impairment in a population
      of elderly patients with hip fracture. METHODS: A case-control study compared 96
      patients diagnosed with hip fracture to a randomly selected control group of 103
      patients without hip fracture. Inclusion criteria for the case group were as
      follows: patients aged 60 years and over with a hip fracture. Clinical assessment
      included visual acuity and ophthalmic examination. RESULTS: Forty-three patients
      with hip fracture had a visual impairment compared to only 12 patients in the
      control group. Visual impairment was a significant risk factor for hip fracture
      (OR = 6.15; 95% CI 2.98-12.69). Twenty-seven hip fracture patients had an
      uncorrected refractive error compared to only 15 controls (OR = 2.78; 95% CI 0.92
      8.35). There was no significant difference of dense cataract between both groups
      (OR = 2.28; 95% CI 0.75-6.93). Fourteen hip fracture patients had a macular
      degeneration compared to only 8 controls (OR = 5.63; 95% CI 1.57-20.18), and 10
      patients had suspicion of glaucoma compared to only 5 controls (OR = 10.65; 95%
      CI 2.21-51.3). CONCLUSION: Visual impairment was significantly associated with an
      increased risk of hip fracture in elderly people. There are many etiologies that
      may contribute to hip fractures, most notably refractive error, cataract, macular
      degeneration and glaucoma.

PMID- 25378037
TI  - Examination of the influence of leptin and acute metabolic challenge on RFRP-3
      neurons of mice in development and adulthood.
AB  - BACKGROUND: The neuropeptide RFamide-related peptide-3 (RFRP-3; mammalian
      ortholog to gonadotropin-inhibiting hormone) can inhibit luteinizing hormone (LH)
      release and increases feeding, but the regulation and development of RFRP-3
      neurons remains poorly characterized, especially in mice. METHODS AND RESULTS: We
      first confirmed that peripheral injections of murine RFRP-3 peptide could
      markedly suppress LH secretion in adult mice, as in other species. Second, given
      RFRP-3's reported orexigenic properties, we performed double-label in situ
      hybridization for metabolic genes in Rfrp neurons of mice. While Rfrp neurons did
      not readily coexpress neuropeptide Y, thyrotropin-releasing hormone, or MC4R, a
      small subset of Rfrp neurons did express the leptin receptor in both sexes.
      Surprisingly, we identified no changes in Rfrp expression or neuronal activation
      in adult mice after acute fasting. However, we determined that Rfrp mRNA levels
      in the dorsal-medial nucleus were significantly reduced in adult obese (Ob) mice
      of both sexes. Given the lower Rfrp levels observed in adult Ob mice, we asked
      whether leptin might also regulate RFRP-3 neuron development. Rfrp gene
      expression changed markedly over juvenile development, correlating with the
      timing of the juvenile 'leptin surge' known to govern hypothalamic feeding
      circuit development. However, the dramatic developmental changes in juvenile Rfrp
      expression did not appear to be leptin driven, as the pattern and timing of Rfrp
      neuron development were unaltered in Ob juveniles. CONCLUSION: Leptin status
      modulates RFRP-3 expression in adulthood, but is not required for normal
      development of the RFRP-3 system. Leptin's regulation of adult RFRP-3 neurons
      likely occurs primarily via indirect signaling, and may be secondary to obesity,
      as only a small subset of RFRP-3 neurons express the long form of the leptin
      receptor (LepRb).

PMID- 25378039
TI  - Pediatric airway management in the emergency department: in urgent need of CPR.

PMID- 25378038
TI  - Metamizole-induced agranulocytosis revisited: results from the prospective Berlin
      Case-Control Surveillance Study.
AB  - PURPOSE: Treatment with metamizole (dipyrone) has steadily increased in Germany
      over the last decade. The consequences of this increase for metamizole-induced
      agranulocytosis (MIA) are unclear. The present study addressed this topic using
      data from the Berlin Case-Control Surveillance Study. METHODS: Adult patients
      (>=18 years of age) with acute nonchemotherapy-induced agranulocytosis were
      identified by active surveillance in all 51 Berlin hospitals between 2000 and
      2010. Cases related to metamizole were ascertained applying the drug causality
      criteria of the World Health Organization. The incidence rate of MIA was
      calculated and standardised by age and sex based on the German standard
      population in 2010. RESULTS: Twenty-six MIA cases out of 88 (30 %) patients with
      validated agranulocytosis were ascertained. The incidence of MIA was 0.96 (95 %
      confidence interval (CI) 0.95-0.97) cases per million per year. The median age of
      MIA cases was 50 years (quartile (Q)1 31 years; Q3 68 years) and 19 (73 %) of
      them were women. In 17 (65 %) cases, neutrophil granulocytes dropped below the
      value of 0.1 * 10(9) cells/L with three patients suffering from sepsis. Headache
      and postoperative pain were the most frequent indications for metamizole in
      outpatients (n = 16) and inpatients (n = 10), respectively. The median treatment
      duration was 6 days (Q1 4 days; Q3 19 days). CONCLUSIONS: MIA persists as a
      severe condition in current pharmacotherapy. The continuous increase of
      metamizole applications should be critically assessed, especially in regard to
      indications in the outpatient setting and with respect to metamizole treatment
      duration.

PMID- 25378040
TI  - Is anesthetic exposure in early life associated with ADHD?

PMID- 25378041
TI  - Novel use of Foley catheter to reduce leak around endotracheal tube in a child
      with temporo-mandibular joint ankylosis.

PMID- 25378042
TI  - The pharmacology of resuscitation training--time for a new treatment plan.

PMID- 25378043
TI  - Retrospective evaluation of antimicrobial prophylaxis in prevention of surgical
      site infection in the pediatric population.

PMID- 25378044
TI  - Reply to comments on our paper 'Does the Miller blade truly provide a better
      laryngoscopic view and intubating conditions than the Macintosh blade in small
      children?'.

PMID- 25378045
TI  - Three-finger tracheal palpation to guide endotracheal tube depth in children.

PMID- 25378046
TI  - Harm attributable to research distraction? Challenging conclusions on caudal
      epinephrine.

PMID- 25378048
TI  - Actinokineospora mzabensis sp. nov., a novel actinomycete isolated from Saharan
      soil.
AB  - A novel actinomycete strain, designated PAL84, was isolated from a Saharan soil
      sample collected from Beni-Isguen, Ghardaia (South of Algeria). This strain was
      studied for its taxonomic position using a polyphasic approach and was identified
      as a member of the genus Actinokineospora. Phylogenetic analysis showed that
      strain PAL84 had 16S rRNA gene sequence similarities with members of the genus
      Actinokineospora ranging from 96.2 % (Actinokineospora inagensis DSM 44258(T)) to
      97.8 % (Actinokineospora baliensis NBRC 104211(T)). The strain was observed to
      produce pinkish-purple aerial mycelium and purplish red substrate mycelium, which
      fragmented readily into chains of non-motile elements. The optimum growth
      temperature and pH were found to be 25-30  degrees C and 5.0-7.0, respectively.
      The cell-wall hydrolysate of strain PAL84 was found to contain meso
      diaminopimelic acid and the diagnostic whole-cell sugars were identified as
      arabinose and galactose. The predominant menaquinone was identified as MK-9 (H4).
      The major fatty acids were found to be iso-C16:0, iso-C15:0, iso-C16:1 H and iso
      C16:0 2OH. The diagnostic phospholipid detected was phosphatidylethanolamine. The
      genotypic and phenotypic data show that the strain represents a novel species of
      the genus Actinokineospora, for which the name Actinokineospora mzabensis sp.
      nov. is proposed, with the type strain PAL84(T) (=DSM 45961(T) = CECT 8578(T)). 

PMID- 25378049
TI  - Nutrient-dependent growth defects and mutability of mutators in Escherichia coli.
AB  - So-called mutators emerge when mismatch repair and proofreading mechanisms are
      defective. Mutators not only accelerate the accumulation of mutations that are
      beneficial for adaptation but also cause a large number of deleterious mutations
      that are disadvantageous for cell growth. However, such growth defects may be
      compensated by nutrient availability. How the growth burden is associated with
      high mutability in relation to nutritional variation is an intriguing question.
      To address this question, we constructed a variety of Escherichia coli mutator
      strains through combinatorial deletions of mismatch repair and proofreading genes
      and quantitatively evaluated their growth and mutation rates under different
      nutritional conditions. Growth defects caused by high mutation rates were
      commonly observed in all mutators, and these defects were alleviated by nutrient
      supplementation in most mutators. In addition, the mutation rates of the mutators
      fluctuated greatly in response to nutritional conditions, in contrast to the
      nearly constant mutation rate of the wild-type strain under varying nutritional
      conditions. The results showed conditional growth defects and nutrition-sensitive
      mutability as general features of mutators. This study indicates the importance
      of modulating mutability in response to changing nutrient conditions to minimize
      the risk of extinction due to genetic load. 

PMID- 25378050
TI  - Change in storage symptoms following laser prostatectomy: comparison between
      photoselective vaporization of the prostate (PVP) and holmium laser enucleation
      of the prostate (HoLEP).
AB  - PURPOSE: To compare serial changes of postoperative storage symptoms between PVP
      and HoLEP, and to identify the predictors influencing postoperative improvement
      of storage symptoms. METHODS: A total of 486 men (PVP group: 213 cases; HoLEP
      group: 273 cases), in whom 12-month follow-up data were available, were included
      in this retrospective study. Surgical outcomes were evaluated at 1-, 3-, 6-, and
      12 months postoperatively using the IPSS, uroflowmetry with post-void residual
      urine volume (PVR) and serum PSA levels. Improvement of storage symptoms was
      defined as a reduction by >=50 % of the subtotal storage symptom score
      postoperatively compared to baseline. RESULTS: In both PVP and HoLEP groups,
      total IPSS, quality-of-life index, frequency score, nocturia score, maximum flow
      rate and PVR were significantly decreased compared to baseline starting from 1
      month after surgery. Whereas urgency score was numerically increased compared to
      baseline at 1 month after PVP, it was reduced compared to baseline at 1 month
      after HoLEP. While the subtotal storage symptom score was significantly decreased
      compared to baseline starting from 3 months after PVP, it was significantly
      reduced starting from 1 month after HoLEP. On logistic regression analysis, a
      higher baseline subtotal storage symptom score was the only independent predictor
      of improvement in storage symptoms after PVP or HoLEP. CONCLUSIONS: Our data
      suggest that improvement in storage symptoms after HoLEP begins earlier than that
      after PVP. Also, this study indicates that patients with more severe baseline
      storage symptoms have a higher likelihood of improvement after PVP or HoLEP
      compared to those with less severe symptoms.

PMID- 25378052
TI  - Influence of work values and personality traits on intent to stay among nurses at
      various types of hospital in Taiwan.
AB  - AIM: In this study, the influence of work values and personality traits on the
      intent to stay at work was examined among nurses in Taiwan. BACKGROUND: No
      empirical studies in this area have been conducted in the nursing industry.
      METHODS: A cross-sectional predictive study was performed during 2012 with 1246
      nurses recruited from three different types of hospital located in northeastern
      Taiwan. A structured questionnaire based on the 5-factor model was used. Multiple
      regression analyses were used to investigate the various factors associated with
      the intent to stay at work among nurses. RESULTS: The overall response rate was
      85%. The nurses who had a high level of intent to stay at work were significantly
      more likely to be in senior roles; exhibited positive work values,
      conscientiousness, emotional stability; and worked at a non-religious hospital.
      CONCLUSION: Age, the role of work values, personality traits and type of hospital
      were crucial in enhancing the level of intent to stay at work. IMPLICATIONS FOR
      NURSING MANAGEMENT: The study findings provide evidence for managers to develop
      an optimal strategy for nurses with specific personality traits and highly
      positive work values, which can guide the recruitment and retention of nurses.

PMID- 25378053
TI  - A physiologically based pharmacokinetic model for quinoxaline-2-carboxylic acid
      in rats, extrapolation to pigs.
AB  - A multi-compartment physiologically based pharmacokinetic (PBPK) model to
      describe the disposition of cyadox (CYX) and its metabolite quinoxaline-2
      carboxylic acid (QCA) after a single oral administration was developed in rats
      (200 mg/kg b.w. of CYX). Considering interspecies differences in physiology and
      physiochemistry, the model efficiency was validated by pharmacokinetic data set
      in swine. The model included six compartments that were blood, muscle, liver,
      kidney, adipose, and a combined compartment for the rest of tissues. The model
      was parameterized using rat plasma and tissue concentration data that were
      generated from this study. Model simulations were achieved using a commercially
      available software program (ACSLXL ibero version 3.0.2.1). Results supported the
      validity of the model with simulated tissue concentrations within the range of
      the observations. The correlation coefficients of the predicted and
      experimentally determined values for plasma, liver, kidney, adipose, and muscles
      in rats were 0.98, 0.98, 0.98, 0.99, and 0.95, respectively. The rat model
      parameters were then extrapolated to pigs to estimate QCA disposition in tissues
      and validated by tissue concentration of QCA in swine. The correlation
      coefficients between the predicted and observed values were over 0.90. This model
      could provide a foundation for developing more reliable pig models once more data
      are available.

PMID- 25378051
TI  - Insulin-like genes in ascidians: findings in Ciona and hypotheses on the
      evolutionary origins of the pancreas.
AB  - Insulin plays an extensively characterized role in the control of sugar
      metabolism, growth and homeostasis in a wide range of organisms. In vertebrate
      chordates, insulin is mainly produced by the beta cells of the endocrine
      pancreas, while in non-chordate animals insulin-producing cells are mainly found
      in the nervous system and/or scattered along the digestive tract. However, recent
      studies have indicated the notochord, the defining feature of the chordate
      phylum, as an additional site of expression of insulin-like peptides. Here we
      show that two of the three insulin-like genes identified in Ciona intestinalis,
      an invertebrate chordate with a dual life cycle, are first expressed in the
      developing notochord during embryogenesis and transition to distinct areas of the
      adult digestive tract after metamorphosis. In addition, we present data
      suggesting that the transcription factor Ciona Brachyury is involved in the
      control of notochord expression of at least one of these genes, Ciona insulin
      like 2. Finally, we review the information currently available on insulin
      producing cells in ascidians and on pancreas-related transcription factors that
      might control their expression.

PMID- 25378054
TI  - Gremlin1 preferentially binds to bone morphogenetic protein-2 (BMP-2) and BMP-4
      over BMP-7.
AB  - Gremlin (Grem1) is a member of the DAN family of secreted bone morphogenetic
      protein (BMP) antagonists. Bone morphogenetic protein-7 (BMP-7) mediates
      protective effects during renal fibrosis associated with diabetes and other renal
      diseases. The pathogenic mechanism of Grem1 during diabetic nephropathy (DN) has
      been suggested to be binding and inhibition of BMP-7. However, the precise
      interactions between Grem1, BMP-7 and other BMPs have not been accurately
      defined. In the present study, we show the affinity of Grem1 for BMP-7 is lower
      than that of BMP-2 and BMP-4, using a combination of surface plasmon resonance
      and cell culture techniques. Using kidney proximal tubule cells and HEK (human
      embryonic kidney)-293 cell Smad1/5/8 phosphorylation and BMP-dependent gene
      expression as readouts, Grem1 consistently demonstrated a higher affinity for BMP
      2>BMP-4>BMP-7. Cell-associated Grem1 did not inhibit BMP-2- or BMP-4-mediated
      signalling, suggesting that Grem1-BMP-2 binding occurred in solution, preventing
      BMP receptor activation. These data suggest that Grem1 preferentially binds to
      BMP-2 and this may be the dominant complex in a disease situation where levels of
      Grem1 and BMPs are elevated. 

PMID- 25378056
TI  - Achieving balanced intermixed and pure crystalline phases in PDI-based non
      fullerene organic solar cells via selective solvent additives.
AB  - Herein, balanced intermixed and pure crystalline phases in N,N'-bis(1
      ethylpropyl)-perylene-3,4,9,10-tetracarboxylic diimide (EP-PDI)-based non
      fullerene organic solar cells (OSCs) were achieved via selective solvent
      additives (SAs). Poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene
      2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] (PTB7)
      and 7,7'-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b']dithiophene-2,6-diyl)bis(6
      fluoro-4-(5'-hexyl-[2,2'-bithiophen]-5-yl)benzo[c][1,2,5]thiadiazole) (F-DTS)
      possessing different compatibilities with EP-PDI were selected as model systems
      to investigate the guideline of SAs selection for different non-fullerene-based
      systems. According to the solubility parameter difference (Deltadelta) between EP
      PDI and SAs, five different SAs were divided into two types: (I) strong
      intermolecular interactions with EP-PDI molecules (with Deltadelta values less
      than 5 MPa(1/2)), (II) weak intermolecular interactions with EP-PDI molecules
      (with large Deltadelta values). For PTB7:EP-PDI system with large and obvious
      phase separation, the introduction of type (II) SAs provided extra interactions
      with EP-PDI molecules, thus effectively reducing EP-PDI aggregate domains and
      increasing intermixed fractions. The incorporation of type (II) SAs resulted in a
      greater yield of dissociated polarons, and the final device efficiency increased
      from 0.02% to 1.65%. On the contrary, for finely mixed F-DTS:EP-PDI systems, type
      (I) SAs were considerably more effective because of the fact that the required
      pure crystalline phases were readily induced by the unfavorable interactions. The
      charge transport pathways optimized by type (I) SAs improved device efficiency
      from 0.18% to 2.82%. Hence, by processing selective SAs, the fraction of
      intermixed and pure crystalline phases for PDI-based non-fullerene OSCs can be
      well regulated; therefore, the final performance for both systems can be
      significantly improved. 

PMID- 25378055
TI  - IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1
      and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.
AB  - Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a
      crucial role in modulating neuronal function and synaptic plasticity in the adult
      brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple
      anomalies in the inner ear and spiral ganglion. An issue that remains unknown is
      whether, in addition to these peripheral abnormalities, IGF-1 deficiency also
      results in structural changes along the central auditory pathway that may
      contribute to an imbalance between excitation and inhibition, which might be
      reflected in abnormal auditory brainstem responses (ABR). To assess such a
      possibility, we evaluated the morphological and physiological alterations in the
      cochlear nucleus complex of the adult mouse. The expression and distribution of
      the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory
      transporter (VGAT), which were used as specific markers for labeling excitatory
      and inhibitory terminals, and the involvement of the activity-dependent myocyte
      enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses
      were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial
      deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in
      the cochlear nucleus area and cell size along with cell loss in the cochlear
      nuclei of the deficient mouse. Additionally, our results demonstrate that there
      is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of
      MEF2 transcription factors together with increased wave II amplitude in the ABR
      recording. Our observations provide evidence of an abnormal neuronal
      cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that
      the increased efficacy of glutamatergic synapses might be mediated by MEF2
      transcription factors. 

PMID- 25378057
TI  - Embryonic development of fin spines in Callorhinchus milii (Holocephali);
      implications for chondrichthyan fin spine evolution.
AB  - Fin spines are commonly known from fossil gnathostomes (jawed vertebrates) and
      are usually associated with paired and unpaired fins. They are less common among
      extant gnathostomes, being restricted to the median fins of certain
      chondrichthyans (cartilaginous fish), including chimaerids (elephant sharks) and
      neoselachians (sharks, skates, and rays). Fin spine growth is of great interest
      and relevance but few studies have considered their evolution and development. We
      investigated the development of the fin spine of the chimaerid Callorhinchus
      milii using stained histological sections from a series of larval, hatchling, and
      adult individuals. The lamellar trunk dentine of the Callorhinchus spine first
      condenses within the mesenchyme, rather than at the contact surface between
      mesenchyme and epithelium, in a manner more comparable to dermal bone formation
      than to normal odontode development. Trabecular dentine forms a small component
      of the spine under the keel; it is covered externally with a thin layer of
      lamellar trunk dentine, which is difficult to distinguish in sectioned adult
      spines. We suggest that the distinctive characteristics of the trunk dentine may
      reflect an origin through co-option of developmental processes involved in dermal
      bone formation. Comparison with extant Squalus and a range of fossil
      chondrichthyans shows that Callorhinchus is more representative than Squalus of
      generalized chondrichthyan fin-spine architecture, highlighting its value as a
      developmental model organism. 

PMID- 25378058
TI  - A Fluorescent Indicator for Imaging Lysosomal Zinc(II) with Forster Resonance
      Energy Transfer (FRET)-Enhanced Photostability and a Narrow Band of Emission.
AB  - We demonstrate a strategy to transfer the zinc(II) sensitivity of a
      fluoroionophore with low photostability and a broad emission band to a bright and
      photostable fluorophore with a narrow emission band. The two fluorophores are
      covalently connected to afford an intramolecular Forster resonance energy
      transfer (FRET) conjugate. The FRET donor in the conjugate is a zinc(II)
      sensitive arylvinylbipyridyl fluoroionophore, the absorption and emission of
      which undergo bathochromic shifts upon zinc(II) coordination. When the FRET donor
      is excited, efficient intramolecular energy transfer occurs to result in the
      emission of the acceptor boron dipyrromethene (4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene or BODIPY) as a function of zinc(II) concentration. The broad emission
      band of the donor/zinc(II) complex is transformed into the strong, narrow
      emission band of the BODIPY acceptor in the FRET conjugates, which can be
      captured within the narrow emission window that is preferred for multicolor
      imaging experiments. In addition to competing with other nonradiative decay
      processes of the FRET donor, the rapid intramolecular FRET of the excited FRET
      conjugate molecule protects the donor fluorophore from photobleaching, thus
      enhancing the photostability of the indicator. FRET conjugates 3 and 4 contain
      aliphatic amino groups, which selectively target lysosomes in mammalian cells.
      This subcellular localization preference was verified by using confocal
      fluorescence microscopy, which also shows the zinc(II)-enhanced emission of 3 and
      4 in lysosomes. It was further shown using two-color structured illumination
      microscopy (SIM), which is capable of extending the lateral resolution over the
      Abbe diffraction limit by a factor of two, that the morpholino-functionalized
      compound 4 localizes in the interior of lysosomes, rather than anchoring on the
      lysosomal membranes, of live HeLa cells.

PMID- 25378059
TI  - Optimal duration of allergen immunotherapy in children with dust mite respiratory
      allergy.
AB  - BACKGROUND: Subcutaneous immunotherapy (SCIT) discontinuation data in children
      remain scarce. OBJECTIVE: We sought for differences in the clinical efficacy of 3
      vs. 5 yr of SCIT in children with dust mite respiratory allergy. METHODS: We
      performed a 5-yr, phase IV prospective study. After the first year, the patients
      were randomized to 3 (IT3) or 5 yr of treatment (IT5). Efficacy was assessed at
      3rd and 5th year by symptom and medication scores and visual analog scales (VAS).
      Skin tests with common allergens and in vitro assessments were also performed.
      RESULTS: Eighty-one children (mean age: 9 yr) were randomly assigned to 3 (IT3:
      41) or 5 yr (IT5: 40) of immunotherapy. After 3 years, rhinitis global scores
      decreased in IT3 (44%; p = 0.002) and in IT5 (50%; p = 0.001). Asthma global,
      symptom and medication scores decreased by 100% in IT3 (p = 0.001) and IT5 (p =
      0.001). VAS scores also diminished significantly (IT3: 70%, p = 0.001; IT5:
      62.5%; p = 0.001). At 5th year, global rhinitis scores were reduced an additional
      30% in IT5 children. Comparisons between both groups did not show differences in
      rhinitis (p = 0.055), asthma global scores (p = 0.948) or VAS scores at 5th year.
      Twenty percent of IT5 (p = 0.002) and 7% of IT3 children (p = 0.705) developed
      new sensitizations. At 5th year, sIgG4 determinations decreased in IT3 without
      significant variations in IT5. CONCLUSIONS: Three years of SCIT induced
      significant improvement in children with dust mite respiratory allergy, but a 5
      yr course added clinical improvement in rhinitis.

PMID- 25378060
TI  - Roscovitine-treated HeLa cells finalize autophagy later than apoptosis by
      downregulating Bcl-2.
AB  - The cell cycle is tightly regulated by the family of cyclin-dependent kinases
      (CDKs). CDKs act as regulatory factors on serine and threonine residues by
      phosphorylating their substrates and cyclins. CDK-targeting drugs have previously
      demonstrated promising effects as cancer therapeutics both in vitro and in vivo.
      Roscovitine, a purine-derivative and specific CDK inhibitor, has been
      demonstrated to arrest the cell cycle and induce apoptosis in a number of
      different cancer cell lines, including HeLa cervical cancer cells. In the present
      study, roscovitine was able to decrease both the cell viability and cell survival
      as well as induce apoptosis in a dose-dependent manner in HeLa cells by
      modulating the mitochondrial membrane potential. The decrease of anti-apoptotic B
      cell lymphoma 2 (Bcl-2) and Bcl-2 extra large protein expression was accompanied
      by the increase in pro-apoptotic Bcl-2-associated X protein and P53-upregulated
      modulator of apoptosis expression. The marked decrease in Bcl-2 following
      exposure to roscovitine (20 uM) for 48 h prompted us to determine the autophagic
      regulation. The outcome revealed that roscovitine triggered Beclin-1
      downregulation and microtubule-associated light chain 3 cleavage starting from 12
      h of incubation. Another biomarker of autophagy, p62, a crucial protein for
      autophagic vacuole formation, was diminished following 48 h. In addition,
      monodansyl cadaverin staining of autophagosomes also confirmed the autophagic
      regulation by roscovitine treatment. The expression levels of different Bcl-2
      family members determined whether apoptosis or autophagy were induced following
      incubation with roscovitine for different time periods. Downregulation of pro
      apoptotic Bcl-2 family members indicated induction of apoptosis, while the
      downregulation of anti-apoptotic Bcl-2 family members rapidly induced
      autophagosome formation in HeLa cells.

PMID- 25378061
TI  - Targeting DNA with small molecules: a comparative study of a library of azonia
      aromatic chromophores.
AB  - A library of azonia aromatic cations has been studied in order to gain insights
      into the effect of the size, shape and charge distribution on the fluorescence,
      DNA interactions and DNA sequence selectivity properties. Fluorescence-based
      thermal denaturation experiments, spectrofluorimetric titrations, circular
      dichroism measurements and theoretical simulations have shown that some of the
      studied chromophores have interesting fluorescence properties and two of them
      also show a consistent DNA-binding ability by intercalation, with a potential
      preference for AT-rich sequences. 

PMID- 25378062
TI  - Influence of carbon monoxide on the colour stability of defrosted yellowfin tuna
      (Thunnus albacares) muscle stored under aerobic and anaerobic conditions.
AB  - BACKGROUND: The use of carbon monoxide (CO) and various packaging types has been
      suggested to improve/stabilise the colour and oxidative processes of red meats,
      thereby improving the retail value and revenue. The main aim of this study was to
      investigate the influence of packaging type and CO treatment on the colour and
      oxidative stability of tuna. RESULTS: The addition of CO significantly increased
      the redness (a(*) ) of the tuna steaks but the redness was not equally stable for
      all treatments. The aerobically packaged steaks showed a temporal decrease in
      redness while the redness of anaerobically packaged steaks remained relatively
      stable. The addition of CO did not significantly affect (P >0.05) the brownness
      (b(*) ) (with one exception) and lightness (L(*) ) of the steaks. The
      anaerobically packaged steaks showed a significant difference (P <0.05) in the
      b(*) values. No significant differences (P >0.05) in lipid or protein oxidation
      were observed between treatments. The aerobically packaged steaks had a
      significant temporal increase (P <0.05) in lipid oxidation while no such trend
      was apparent in the anaerobically packaged steaks. Protein oxidation remained
      relatively stable over time for both aerobically and anaerobically packaged
      steaks. CONCLUSION: Storing CO treated tuna steaks in anaerobic packaging can
      improve the oxidative and colour stability of tuna. Such treatment can reduce
      spoilage and wastage thereby potentially increasing revenue.

PMID- 25378063
TI  - Microengineered in vitro model of cardiac fibrosis through modulating
      myofibroblast mechanotransduction.
AB  - Cardiac fibrosis greatly impairs normal heart function post infarction and there
      is no effective anti-fibrotic drug developed at present. The current therapies
      for cardiac infarction mainly take effect by eliminating occlusion in coronary
      artery by thrombolysis drugs, vascular stent grafting or heart bypass operation,
      which are capable to provide sufficient blood flow for intact myocardium yet
      showed subtle efficacy in ameliorating fibrosis condition. The advances of in
      vitro cell/tissue models open new avenues for drug assessment due to the low
      cost, good controllability and availability as well as the convenience for
      operation as compared to the animal models. To our knowledge, no proper
      biomimetic in vitro cardiac fibrosis model has been reported yet. Here we
      engineered an in vitro cardiac fibrosis model using heart-derived fibroblasts,
      and the fibrogenesis was recapitulated by patterning the substrate rigidity which
      mimicked the mechanical heterogeneity of myocardium post-infarction. Various
      biomarkers for cardiac fibrosis were assayed to validate the biomimicry of the
      engineered platform. Subsequent addition of Rho-associated protein kinase (ROCK)
      pathway inhibitor reduced the ratio of myofibroblasts, indicating the feasibility
      of applying this platform in screening anti-fibrosis drugs. 

PMID- 25378064
TI  - Imperatorin is a mechanism-based inactivator of CYP2B6.
AB  - Imperatorin (IMP) is the major active ingredient in many common medicinal herbs.
      We examined the irreversible inhibitory effect of IMP on CYP2B6. IMP produced a
      time- and concentration-dependent inactivation of CYP2B6. About 70% of activity
      of CYP2B6 was suppressed after its incubation with 1.5 MUM IMP for 9 minutes. KI
      and kinact were found to be 0.498 MUM and 0.079 min(-1), respectively. The loss
      of CYP2B6 activity required the presence of NADPH. Glutathione and
      catalase/superoxide dismutase showed little protection against the IMP-induced
      enzyme inactivation. Ticlopidine, a substrate of CYP2B6, showed protection of the
      enzyme against the inactivation induced by IMP. The estimated partition ratio of
      the inactivation was approximately 4. Additionally, a gamma-ketoenal intermediate
      was identified in microsomal incubations with IMP. CYP1A2, CYP2A6, CYP2B6,
      CYP2D6, CYP2E1, CYP3A4, and CYP3A5 were found to be involved in bioactivation of
      IMP. In conclusion, IMP is a mechanism-based inactivator of CYP2B6. The formation
      of gamma-ketoenal intermediate may account for the enzyme inactivation. 

PMID- 25378065
TI  - Control of tissue-localized immune responses by human regulatory T cells.
AB  - Treg cells control immune responses to self and nonharmful foreign antigens.
      Emerging data from animal models indicate that Treg cells function in both
      secondary lymphoid organs and tissues, and that these different microenvironments
      may contain specialized subsets of Treg cells with distinct mechanisms of action.
      The design of therapies for the restoration of tissue-localized immune
      homeostasis is dependent upon understanding how local immune responses are
      influenced by Treg cells in health versus disease. Here we review the current
      state of knowledge about human Treg cells in four locations: the skin, lung,
      intestine, and joint. Despite the distinct biology of these tissues, there are
      commonalities in the biology of their resident Treg cells, including phenotypic
      and functional differences from circulating Treg cells, and the presence of
      cytokine-producing (e.g. IL-17(+)) FOXP3(+) cells. We also highlight the
      challenges to studying tissue Treg cells in humans, and opportunities to use new
      technologies for the detailed analysis of Treg cells at the single-cell level. As
      emerging biological therapies are increasingly targeted toward tissue-specific
      effects, it is critical to understand their potential impact on local immune
      regulation.

PMID- 25378066
TI  - Exploring the "weight" of food cravings and thought suppression among Cuban
      adults.
AB  - PURPOSE: The current study aimed to analyze individual differences on food
      cravings, intrusive-related thoughts and its suppression between normal weight
      and overweight/obese Cuban adults. METHODS: Participants were 1,184 individuals
      from general population, aged between 18 and 64 years (M = 32.89; SD = 12.87),
      with 69.1 % females. All participants answered a set of questionnaires and
      provided demographic, anthropometric and clinical data. RESULTS: Overweight/obese
      individuals had higher mean scores than normal weight individuals on food
      cravings (including its nine dimensions) and food and body weight/shape thought
      suppression. Large effect sizes were found for body weight/shape thoughts
      suppression and lack of control over eating, where overweight and obese
      individuals showed the highest scores. This trend was also found for food
      thoughts suppression, food cravings trait, cue-dependent eating, preoccupation
      with food and guilty feelings, with effect sizes from medium to large. Finally,
      medium effect sizes were observed for intention to eat and negative affect.
      CONCLUSION: Overweight/obese individuals experienced more food cravings and food
      and body weight/shape thought suppression than normal weight individuals among
      Cuban adults.

PMID- 25378074
TI  - WAVE3 promotes epithelial-mesenchymal transition of gastric cancer through
      upregulation of Snail.
AB  - WAVE3, an actin cytoskeleton remodeling protein overexpressed in many kinds of
      cancers, has been associated with a lot of metastatic diseases. However, the role
      and mechanisms of the high expression of WAVE3 in human gastric cancer has not
      been fully elucidated. Here we demonstrated that WAVE3 was expressed in all six
      kinds of gastric-cancer cell lines: BGC-823, SGC-7901, AGS, MGC803, MKN28 and
      MKN45. Furthermore, a correlation was found between aggressiveness of these cell
      lines and expression of WAVE3. Next, we investigated the role of WAVE3 in SGC
      7901 cells and found that upregulating WAVE3 could promote the migration,
      invasion and proliferation of SGC-7901 cells in vitro. It has been reported that
      WAVE3 could induce cancer invasion and metastasis by participating epithelial
      mesenchymal transition (EMT). However, the mechanisms are not entirely clear. In
      this study we showed that elevated WAVE3 levels could induce EMT in SGC-7901
      cells by dampening the expression of E-cadherin while increasing the expression
      of vimentin. Elevated WAVE3 levels could also improve the expression of
      transcription factor Snail. In addition, downregulating Snail could particularly
      reduce EMT and the metastasis, invasion and proliferation activity in SGC-7901
      cells elevated by overexpression of WAVE3. Taken together, we demonstrated that
      WAVE3 promoted gastric-cancer-cells migration and invasion by taking part in EMT
      via upregulation of Snail. WAVE3 could be a useful target for gastric-cancer
      prevention and therapy. 

PMID- 25378075
TI  - The Multisystemic and Multilevel Investigation of the Expanded Therapeutic
      Alliance-Psychological Functioning Relationship in Individual Therapy.
AB  - The expanded therapeutic alliance, consisting of multiple interpersonal alliance
      relationships, is a common factor inherent to the practice of all systemic
      therapies. The following study has three specific aims: (a) Bring an expanded,
      multisystemic emphasis to the study of the therapeutic alliance in individual
      therapy; (b) Understand better the session-by-session relationship between
      alliance and psychological functioning, including distinguishing within-person
      from between-person variability by using multilevel modeling techniques; and (c)
      Explore the role of early attachment relationships and family-of-origin
      experiences in moderating the alliance-psychological functioning relationship.
      Instead of taking only one or two alliance measurements throughout treatment like
      in the majority of previous research, we measured both alliance and psychological
      functioning continuously at each session for 296 subjects. 

PMID- 25378076
TI  - Energy barrier at the N719-dye/CsSnI3 interface for photogenerated holes in dye
      sensitized solar cells.
AB  - This report is to address the question if black gamma-polymorph of cesium tin tri
      iodide (B-gamma-CsSnI3) can be used as a solid-state hole-transport material in
      the conventional DSSCs with the N719 dye to replace the liquid electrolyte as
      reported by I. Chung et al. on Nature 485, 486, (2012). Here we demonstrate
      rigorously that B-gamma-CsSnI3 is not energetically possible to collect
      photogenerated holes because of the large energy barrier at the interface of
      N719/B-gamma-CsSnI3. Therefore, it cannot serve as a hole-transporter for the
      conventional DSSCs although it is a good hole-conducting material. A solution
      based method was employed to synthesize the B-gamma-CsSnI3 polycrystalline thin
      films used for this work. These thin-films were then characterized by X-ray
      diffraction, Hall measurements, optical reflection, and photoluminescence (PL).
      Particularly, spatially resolved PL intensity images were taken after B-gamma
      CsSnI3 was incorporated in the DSSC structure to insure the material integrity.
      The means of ultraviolet photoemission spectroscopy (UPS) was used to reveal why
      B-gamma-CsSnI3 could not act as the substitute of liquid electrolyte in the
      conventional DSSCs. For the completeness, other two related compounds, one is the
      yellow polymorph of CsSnI3 and other is Cs2SnI6 with tetravalent tin instead of
      double-valent tin in CsSnI3 were also investigated by UPS. 

PMID- 25378077
TI  - Bile salt export pump: a sensitive and specific immunohistochemical marker of
      hepatocellular carcinoma.
AB  - AIMS: Bile salt export pump (BSEP) is a transporter expressed exclusively at
      hepatic canaliculi and drives bile-salt efflux. Minimal data exist about BSEP
      expression in tumours. We hypothesized that BSEP immunohistochemistry would be
      specific for hepatocellular carcinoma (HCC). METHODS AND RESULTS: Tissue
      microarrays, including 48 HCC, 41 cholangiocarcinomas and 24 metastatic tumours
      in liver, were immunostained for BSEP. Expression was compared with common
      markers of hepatocytic differentiation including CD10, hepatocyte paraffin-1
      antigen (HepPar-1), carcinoembryonic antigen, arginase-1 (ARG) and glypican-3
      (GPC-3). BSEP expression was assessed in normal tissues. Special attention was
      given to adrenal gland (normal and neoplasia). BSEP was easy to interpret and
      showed no background staining. Canalicular expression was seen in all normal
      livers, but not in other normal tissue. BSEP was 90% sensitive and 100% specific
      for HCC (canalicular in 33 of 43 positive cases). The sensitivity of ARG was
      slightly higher, but specificity was slightly lower (94% for both). HepPar-1 was
      90% sensitive and 97% specific. CD10, polyclonal carcinoembryonic antigen (pCEA)
      and GPC-3 all had lower sensitivity (74, 81 and 54%, respectively). CONCLUSIONS:
      In malignant tumours in the liver, BSEP marking was 100% specific and 90%
      sensitive for HCC. The specificity of BSEP for HCC obviates the need to identify
      a 'canalicular' pattern, which can limit the utility of other canalicular
      markers.

PMID- 25378078
TI  - A novel frameshift mutation of epithelial sodium channel beta-subunit leads to
      Liddle syndrome in an isolated case.
AB  - OBJECTIVE: Liddle syndrome, an autosomal dominant form of monogenic hypertension,
      is attributed to mutations in the genes encoding beta and gamma subunits (SCNN1B
      and SCNN1G) of the epithelial sodium channel (ENaC). The aim of this study was to
      search for pathogenic mutations of SCNN1B and SCNN1G in an adolescent under the
      impression of Liddle syndrome and no family history of hypertension. DESIGN AND
      PATIENTS: We screened the C-terminus of SCNN1B and SCNN1G in an adolescent with
      poorly controlled hypertension who was clinically diagnosed as having Liddle
      syndrome. We also screened for the mutation in his parents, 100 hypertensive
      patients and 100 controls. RESULTS: Genetic analysis of SCNN1B revealed a
      frameshift mutation induced by insertion of an additional cytosine into a string
      of six located between codons 617 and 618, which is predicted to introduce a new
      termination codon at position 621 and produce a protein truncated by 20 amino
      acids. This frameshift mutation was not detected in the patient's parents, the
      100 hypertensive patients or the 100 controls, indicating that this is a de novo
      mutation and not a common genetic polymorphism. There was no mutation of SCNN1G
      in any of the individuals examined. CONCLUSION: Based on direct DNA sequencing,
      we identified a novel frameshift mutation in the betaENaC gene in an isolated
      case of Liddle syndrome. Confirmation of the diagnosis and effective tailored
      treatment in the patient were achieved, implying that genetic testing is a useful
      tool to diagnose Liddle syndrome.

PMID- 25378079
TI  - Vertical epitaxial co5 ge7 nanowire and nanobelt arrays on a thin graphitic layer
      for flexible field emission displays.
AB  - Vertically aligned single-crystalline Co5 Ge7 nanowire (NW) and nanobelt arrays
      are grown on a very thin graphite layer as well as a curved graphite layer with a
      good epitaxial lattice match. Co5 Ge7 NW arrays, thus grown, show very efficient
      field emission properties comparable to those of carbon nanotubes and may be used
      for flexible field emission displays in the future. 

PMID- 25378080
TI  - Altered molecular specificity of surfactant phosphatidycholine synthesis in
      patients with acute respiratory distress syndrome.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening
      critical illness, characterised by qualitative and quantitative surfactant
      compositional changes associated with premature airway collapse, gas-exchange
      abnormalities and acute hypoxic respiratory failure. The underlying mechanisms
      for this dysregulation in surfactant metabolisms are not fully explored. Lack of
      therapeutic benefits from clinical trials, highlight the importance of detailed
      in-vivo analysis and characterisation of ARDS patients according to patterns of
      surfactant synthesis and metabolism. METHODS: Ten patients with moderate to
      severe ARDS were recruited. Most (90%) suffered from pneumonia. They had an
      infusion of methyl-D9-choline chloride and small volume bronchoalveolar lavage
      fluid (BALF) was obtained at 0,6,12,24,48,72 and 96 hours. Controls were healthy
      volunteers, who had BALF at 24 and 48 hours after methyl-D9-choline infusion.
      Compositional analysis and enrichment patterns of stable isotope labelling of
      surfactant phosphatidylcholine (PC) was determined by electrospray ionisation
      mass spectrometry. RESULTS: BALF of patients with ARDS consisted of diminished
      total PC and fractional PC16:0/16:0 concentrations compared to healthy controls.
      Compositional analysis revealed, reductions in fractional compositions of
      saturated PC species with elevated levels of longer acyl chain unsaturated PC
      species. Molecular specificity of newly synthesised PC fraction showed time
      course variation, with lower PC16:0/16:0 composition at earlier time points, but
      achieved near equilibrium with endogenous composition at 48 hours after methyl-D9
      choline infusion. The enrichment of methyl-D9-choline into surfactant total PC is
      nearly doubled in patients, with considerable variation between individuals.
      CONCLUSIONS: This study demonstrate significant alterations in composition and
      kinetics of surfactant PC extracted from ARDS patients. This novel approach may
      facilitate biochemical phenotyping of ARDS patients according to surfactant
      synthesis and metabolism, enabling individualised treatment approaches for the
      management of ARDS patients in the future.

PMID- 25378081
TI  - Examining the mediating role of cancer-related problems on spirituality and self
      rated health among African American cancer survivors: a report from the American
      Cancer Society's Studies of Cancer Survivors-II.
AB  - OBJECTIVE: African American (AA) cancer survivors report poorer self-rated health
      (SRH) compared to other racial/ethnic groups. Spirituality is often linked to
      positive health outcomes, with AAs reporting greater levels of spirituality. This
      study examined the potential mediating role of cancer-related problems in the
      relationship between spirituality and SRH among AA cancer survivors compared to
      non-African American (non-AA) survivors. METHODS: We analyzed data on 9006 adult
      cancer survivors from the American Cancer Society's Study of Cancer Survivors-II.
      Preliminary analyses compared characteristics of AAs and non-AAs and identified
      significant covariates of SRH. We tested a path model using multi-group
      structural equation modeling (SEM), and then examined race as a moderator.
      RESULTS: Of the three domains of spirituality assessed, AAs had higher levels of
      peace (p < .001) and faith (p < .001), but not meaning, compared to non-AAs; and
      of four domains of cancer-related problems assessed, AAs had greater physical
      distress (p < .001), emotional distress (p < .001), and employment/finance
      problems (p < .001), but not fear of recurrence. In SEM analyses adjusting for
      number of comorbidities and income, race moderated the impact of spirituality and
      cancer-related problems on SRH. Specifically, spirituality had significantly
      stronger associations with cancer-related problems among AAs than non-AAs.
      Spirituality was positively associated with all four domains of cancer-related
      problems, but only physical distress was associated with SRH among AAs.
      CONCLUSIONS: The negative effects of physical distress may attenuate the positive
      effects of spirituality on AA's SRH. Future studies should consider racial/ethnic
      differences in the determinants and conceptualization of SRH, which is a known
      predictor of survival.

PMID- 25378082
TI  - Changes in the sexual function during pregnancy.
AB  - INTRODUCTION: The physiological changes during each trimester of pregnancy have a
      significant impact on women's sexual behavior. AIM: The aim of the work was to
      assess changes in the sexual function during pregnancy. METHODS: The prospective
      study encompassed 520 pregnant women aged between 18 and 45, of whom 168 were
      qualified for the final analysis. The research tool was a purpose-designed
      research questionnaire and the standardized Female Sexual Function Index. MAIN
      OUTCOME MEASURES: To assess changes in the sexual function among pregnant women
      aged 18-45 in the three pregnancy trimesters. RESULTS: All the studied
      parameters, i.e., desire, arousal, lubrication, orgasm, satisfaction, and pain,
      decreased significantly with the progression of pregnancy. Analyzing the
      frequency of sexual intercourse in the studied group before and during pregnancy,
      a statistically significant decrease (P<0.000001) was observed. Sexual desire
      changed statistically significantly (P=0.0004). The direction of change concerned
      decreased sexual desire in the three trimesters compared with the situation
      before pregnancy. Statistical significance was demonstrated for: decreased sexual
      desire (P=0.00007), partner's reluctance (P=0.002), and pregnancy-related changes
      in appearance (P=0.03). CONCLUSIONS: Sexual function was compromised and sexual
      activity decreased as the pregnancy progressed. Changes in the domains of
      arousal, lubrication, and orgasm were particularly notable in primaparae in the
      third trimester of pregnancy. Unsatisfying partner relationship was a significant
      factor affecting the quality of sexual life during pregnancy.

PMID- 25378083
TI  - Unilateral versus bilateral pedicle screw fixation of minimally invasive
      transforaminal lumbar interbody fusion (MIS-TLIF): a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: A few studies focused on unilateral or bilateral pedicle screw (PS)
      fixation of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)
      to treat lumbar degenerative diseases have been published. There is still debate
      over whether one method is superior to another. A systematic review and meta
      analysis of randomized controlled trials (RCT) was performed to compare the
      efficacy of the two methods. METHODS: We searched the established electronic
      literature databases of MEDLINE, EMBASE, Web of Science and the Cochrane Central
      Register of Controlled Trials databases for RCTs comparing the unilateral with
      bilateral pedicle screw fixation of MIS-TLIF. Pooled mean differences (MD) and
      odds ratios (OR) and with 95% CIs were calculated for the outcomes. RESULTS:
      Three RCTs were identified and analyzed. The results showed that there is no
      significant difference between the two methods in terms of postoperative VAS-BP
      score (WMD = -0.09; 95% CI: -0.69 to 0.51; P =0.78), ODI (WMD, -0.09; 95% CI 
      5.85 to 5.67; P =0.98), fusion rate (OR = 2.99; 95% CI 0.55 to 16.38; P = 0.21)
      or complication rate (OR = 1.61, 95% CI: 0.49 to 5.37; P =0.43). Unilateral
      pedicle screw fixation was associated with less blood loss (WMD = -87.83; 95% CI:
      -160.70 to -14.96; P =0.02). CONCLUSIONS: The existing evidence indicate that no
      superiority exists between the two fixation methods of MIS-TLIF in terms of
      functional outcome, fusion rate and complication rate, in spite of that
      unilateral pedicle screw fixation can achieve less blood loss than bilateral
      fixation.

PMID- 25378084
TI  - Does the frequency of respiratory tract infections help to identify humoral
      immunodeficiencies in a primary health-care cohort?
AB  - BACKGROUND: Primary immune deficiency (PID) due to humoral defects is associated
      with recurrent respiratory tract infections (RTIs). Reliable clinical warning
      signs of PID would facilitate early diagnosis and thereby reduce long-term
      complications. The aim of the present study was to evaluate the accuracy of the
      warning sign, 'four or more antibiotic-treated RTIs annually for 3 or more
      consecutive years,' for detecting PID among adults in a primary health-care
      setting. METHODS: Fifty-three cases with 'four or more antibiotic-treated RTIs
      annually for 3 or more consecutive years' were selected from a Swedish primary
      health-care registry of RTIs. In addition, 66 age- and sex-matched controls were
      selected having a maximum of one antibiotic-treated RTI during the period covered
      by the study. Levels of immunoglobulin (Ig) IgG, IgA, IgM, IgG subclasses, and
      IgG antibodies against Haemophilus influenzae and Streptococcus pneumoniae as
      well as the inflammatory markers, C-reactive protein, interleukin (IL)-6 and IL-8
      were determined. RESULTS: IgG subclass deficiencies (IgGsd) were found in 5/53
      (9.4%) of the cases and in 7/66 (10.6%) controls. The most frequent deficiency
      was IgG3sd and this was found in three participants in the case group and seven
      in the control group. The mean level of IgG3 was lower in the control group (p =
      0.02). The mean level of IL-8 was lower in the case group (p = 0.02). CONCLUSION:
      The results show that physicians working in primary health care cannot solely
      rely on the frequency of antibiotic-treated RTIs as a warning sign for the
      detection of common humoral immune deficiencies.

PMID- 25378085
TI  - Oral human papillomavirus (HPV) prevalence in youth and cervical HPV prevalence
      in women attending a youth clinic in Sweden, a follow up-study 2013-2014 after
      gradual introduction of public HPV vaccination.
AB  - During 2009-2011, we reported that the oral and cervical prevalence of human
      papillomavirus (HPV) was high by international standards at 9.3% and 74%,
      respectively, in youth aged 15-23 years attending a youth clinic in Stockholm.
      After gradual introduction of public HPV vaccination during 2007-2012, between
      2013 and 2014, when 73% of the women were HPV-vaccinated, but not necessarily
      before their sexual debut, oral HPV prevalence had dropped to 1.4% as compared
      with 9.3% in 2009-2011 (p < 0.00001). Cervical HPV prevalence was high and common
      cervical high-risk types were HPV51, 56, 59, 73, 16, 39, 52, and 53. However, it
      was shown that HPV16, 31, and 70 were significantly less common among HPV
      vaccinated women than among those who had not received the vaccine.

PMID- 25378086
TI  - Spontaneous arterial calcification: a possible etiology for spontaneous splenic
      rupture in a patient on maintenance hemodialysis.
AB  - Spontaneous splenic rupture (SSR) is a rare condition in contrast to traumatic
      splenic hematoma, and vascular abnormality has rarely mentioned as an etiology in
      SSR with patients who had chronic kidney disease. We reported a 80-year-old
      female whose SSR might be related to splenic arterial calcification.

PMID- 25378087
TI  - Occult bacteraemia is uncommon in febrile infants who appear well, and close
      clinical follow-up is more appropriate than blood tests.
AB  - AIM: The rate of paediatric occult bacteraemia after the introduction of the 13
      valent pneumococcal conjugated vaccine is relatively unknown. We determined the
      rate, and identified isolated pathogens, in children aged three to 36 months who
      presented to a paediatric emergency department with fever, but otherwise appeared
      well. We also analysed the yield of laboratory parameters traditionally
      considered risk factors for occult bacteraemia. METHODS: Children aged three to
      36 months who were febrile, but otherwise appeared well, were included if they
      had blood tests in the paediatric emergency department between April 2010 and
      September 2012. RESULTS: Of the 591 patients, only six (1.0%) had a true
      bacterial pathogen and three of those were Streptococcus pneumoniae (0.5%). None
      of the children with pneumococcal bacteraemia had been immunised. The contaminant
      rate was 2.7%, and an elevated band count was the best predictor of occult
      bacteraemia, with positive and negative likelihood ratios of 10 and 0.4,
      respectively. The yield of the other laboratory parameters was very limited.
      CONCLUSION: In the era of the 13-valent pneumococcal conjugated vaccine, occult
      bacteraemia is an uncommon event in febrile children aged three to 36 who
      otherwise appear well and close follow-up should replace blood analysis in such
      cases.

PMID- 25378089
TI  - Re: "body mass index categories in observational studies of weight and risk of
      death" and "editorial: body mass index and risk of death".

PMID- 25378090
TI  - Flegal et al. reply.

PMID- 25378088
TI  - Novel strategies and underlying protective mechanisms of modulation of vagal
      activity in cardiovascular diseases.
AB  - Cardiovascular disease remains a major cause of disability and death worldwide.
      Autonomic imbalance, characterized by suppressed vagal (parasympathetic) activity
      and increased sympathetic activity, correlates with various pathological
      conditions, including heart failure, arrhythmia, ischaemia/reperfusion injury and
      hypertension. Conventionally, pharmacological interventions, such as beta-blocker
      treatment, have primarily targeted suppressing sympathetic over-activation, while
      vagal modulation has always been neglected. Emerging evidence has documented the
      improvement of cardiac and vascular function mediated by the vagal nerve. Many
      investigators have tried to explore the effective ways to enhance vagal tone and
      normalize the autonomic nervous system. In this review, we attempt to give an
      overview of these therapeutic strategies, including direct vagal activation
      (electrical vagal stimulation, ACh administration and ACh receptor activation),
      pharmacological modulation (adenosine, cholinesterase inhibitors, statins) and
      exercise training. This overview provides valuable information for combination
      therapy, contributing to establishment of a comprehensive system on vagal
      modulation from the aspects of clinical application and lifestyle improvement. In
      addition, the mechanisms contributing to the benefits of enhancing vagal tone are
      diverse and have not yet been fully defined. We endeavour to outline the recent
      findings that advance our knowledge regarding the many favourable effects exerted
      by vagal activation: anti-inflammatory pathways, modulation of NOS and NO
      signalling, regulation of redox state, improvement of mitochondrial biogenesis
      and function, and potential calcium regulation. This review may help to develop
      novel therapeutic strategies targeting enhancing vagal activity for the treatment
      of cardiovascular diseases.

PMID- 25378091
TI  - One-pot construction of multipodal hybrid periodic mesoporous organosilica
      nanoparticles with crystal-like architectures.
AB  - The design of hybrid multipodal PMO (mp-PMO) nanoparticles with crystal-like
      architectures elaborated in a one-pot, two-step process, involving the
      preparation of a benzene-based spherical PMO core followed by the formation of
      ethylene-based rod-shaped PMO pods on these cores is described. 

PMID- 25378092
TI  - Pregnancy outcomes in women with inflammatory bowel disease following exposure to
      thiopurines and antitumor necrosis factor drugs: a systematic review with meta
      analysis.
AB  - Several studies have indicated the harmful effect of flare-up periods in pregnant
      women with inflammatory bowel disease (IBD) on their newborns. Therefore, an
      effective and safe medical treatment during pregnancy is of great concern in IBD
      patients. The aim of this study was to perform a meta-analysis on the outcomes of
      thiopurines use and a systematic review of antitumor necrosis factor (anti-TNF)
      drugs used during pregnancy in women with IBD. The results of cohorts evaluating
      the safety of anti-TNF drugs during pregnancy up to July 2013 were collected and
      analyzed. In the meta-analysis, a total of 312 pregnant women with IBD who used
      thiopurines were compared with 1149 controls (women with IBD who were not treated
      with any medication and women who were exposed to drugs other than thiopurines)
      to evaluate the drug effect on different pregnancy outcomes, including
      prematurity, low birth weight, congenital abnormalities, spontaneous abortion,
      and neonatal adverse outcomes. Results of statistical analysis demonstrated that
      congenital abnormalities were increased significantly in thiopurine-exposed group
      in comparison with control group who did not receive any medicine for IBD
      treatment. The summary odds ratio was 2.95 with 95% confidence interval = 1.03
      8.43 (p = 0.04). We observed no significant differences in occurrence of other
      adverse pregnancy outcomes between compared groups. The results of cohorts
      evaluated the safety of anti-TNF drugs during pregnancy demonstrated no increase
      in occurrence of adverse pregnancy outcomes in comparison with controls except
      for the significant decrease in gestational age of newborns of drug-exposed
      mothers in one trial. In conclusion, a benefit-risk ratio should be considered in
      prescribing or continuing medicinal therapy during pregnancy of IBD patients. 

PMID- 25378093
TI  - Haematological and histopathological effects of apigenin, phloretin and myricetin
      based on uterotrophic assay in immature Wistar female albino rats.
AB  - In this study, it is aimed to determine the histopathological and haematological
      effects of apigenin, phloretin and myricetin on Wistar immature female rats using
      Tier 2 of the uterotrophic assay. The female rats were divided into 17 groups
      with 6 rats in each group. There was a negative control group and positive
      control dose groups that contained 0.07 ug/kg/day, 0.7 ug/kg/day and 7 ug/kg/day
      of ethinyl estradiol (EE), 0.7 ug/kg/day 17alpha-ethinyl estradiol + 1 mg/kg/day
      tamoxifen and genistein. The other dose groups contain 1 mg/kg/day, 10 mg/kg/day
      and 100 mg/kg/day of apigenin, myricetin and phloretin. All chemicals had been
      given to Wistar immature female rats with oral gavage for three consecutive days.
      At the end of the study, blood samples were analysed for haematological
      parameters. Tissue samples that were taken from the liver, kidney, spleen and
      thyroid were histopathologically and histomorphometrically examined. There were
      no significant differences between oil control and other dose groups for
      glomerular histomorphometry. However, there were significant differences for
      thyroid histomorphometry. Especially, 10 and 100 mg/kg/day of phloretin dose
      groups had a significant increase in colloid surface area in thyroid compared
      with the 1 mg/kg/day of phloretin and oil control groups. Significant
      histopathological changes (congestion, degeneration, fibrosis and mononuclear
      cell infiltration) were noted in the tissue specimens obtained from the treatment
      groups compared with the control group. According to the results of the
      haematological analysis of the groups, especially the values of erythrocytes and
      haematocrit were increased significantly in most of the dose groups according to
      the oil control group.

PMID- 25378094
TI  - Assessment of patients who presented to the emergency department with mushroom
      poisoning.
AB  - OBJECTIVE: This study aimed to assess the demographic characteristics, emergency
      department (ED) complaints, laboratory findings, and latent phase periods of
      patients who presented to the ED due to mushroom poisoning (MP) as well as the
      efficacy of conventional and hemofiltration therapies. METHOD: The study was
      conducted on patients who presented to the ED with MP between 2010 and 2012. The
      patient's demographic characteristics, complaints at the ED, latent phases,
      laboratory findings, and treatments of MP cases were evaluated. RESULTS: The mean
      age of patients was 38.03 +/- 15.96, where 63.8% of them were female and 36.2%
      were male. Visits occurred most frequently in the autumn (32.6%). When presenting
      to the ED, the most frequent complaint was nausea-vomiting. The aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), international normalised
      ratio (INR), and blood urea nitrogen values of patients with a latent phase
      between 0 h and 5 h were significantly lower than the values of patients with a
      latent phase between 6 h and 24 h. In this study, 62% of the patients (n = 36)
      had stomach lavage and received activated charcoal. Altogether, 55.2% of the
      patients had received conventional therapy, 37.9% of them received
      hemofiltration, and all of them received supportive treatment. The AST, ALT, and
      INR values of those who had received hemofiltration and conventional therapies
      were significantly higher than of those who received only supportive treatment (p
      < 0.01). CONCLUSION: Hemofiltration, in combination with conventional therapy,
      seems to be an effective treatment for reducing mortality in suspected MP cases
      involving late acting toxins.

PMID- 25378095
TI  - Edible mushroom-related poisoning: A study on circumstances of mushroom
      collection, transport, and storage.
AB  - BACKGROUND: The American Association of Poison Control Center (AAPCC) shows that
      in 2012 there were 0.3% of human exposures involving mushrooms. Only 17% of 6600
      cases were then identified by the species. The present retrospective study was
      designed to identify the epidemiology of mushroom poisoning in adults admitted to
      Krakow's Department of Clinical Toxicology (DCT) from 2002 to 2009. MATERIALS AND
      METHODS: This study was conducted retrospectively after examining the files of
      457 adult patients with wild mushroom poisoning. Mycological analysis was made
      and the species of the poisoning-inducing mushroom was determined. Furthermore,
      the circumstances related to the mushroom gathering, transport, storage,
      preparation, and consumption have been analyzed. RESULTS: The analysis revealed
      that in 400 (87.53%) out of 457 cases, the clinical symptoms were caused by
      ingestion of identified edible mushroom species. The main reason for edible
      mushroom poisoning is associated with their incorrect processing after harvest.
      The analysis of the circumstances of mushroom collection, transport, and storage
      shows that the largest percentage of poisoning was connected with long-term
      storage of mushroom dishes, collecting, and storing them in plastic bags, and
      long storage of mushrooms. CONCLUSION: Based on spore analysis of the gastric
      content, edible mushrooms were responsible for the great majority of mushroom
      poisoning cases admitted to the DCT. The toxicity of edible mushroom is
      associated with proceeding with them during collection, transport, and storage.
      The medical history should be supplemented by questions concerning these
      circumstances. The identification of the mushroom by a mycologist is highly
      desirable.

PMID- 25378096
TI  - Does the addition of visceral manipulation alter outcomes for patients with low
      back pain? A randomized placebo controlled trial.
AB  - BACKGROUND: This study aimed to investigate whether the addition of visceral
      manipulation, to a standard physiotherapy algorithm, improved outcomes in
      patients with low back pain. METHODS: Sixty-four patients with low back pain who
      presented for treatment at a private physiotherapy clinic were randomized to one
      of two groups: standard physiotherapy plus visceral manipulation (n = 32) or
      standard physiotherapy plus placebo visceral manipulation (n = 32). The primary
      outcome was pain (measured with the 0-10 Numerical Pain Rating Scale) at 6 weeks.
      Secondary outcomes were pain at 2 and 52 weeks, disability (measured with the
      Roland-Morris Disability Questionnaire) at 2, 6 and 52 weeks and function
      (measured with the Patient-Specific Functional Scale) at 2, 6 and 52 weeks. This
      trial was registered with the Australia and New Zealand Clinical Trials Registry
      (ACTRN12611000757910). RESULTS: The addition of visceral manipulation did not
      affect the primary outcome of pain at 6 weeks (-0.12, 95% CI = -1.45 to 1.21).
      There were no significant between-group differences for the secondary outcomes of
      pain at 2 weeks or disability and function at 2, 6 or 52 weeks. The group
      receiving addition of visceral manipulation had less pain than the placebo group
      at 52 weeks (mean 1.57, 95% CI = 0.32 to 2.82). Participants were adequately
      blinded to group status and there were no adverse effects reported in either
      group. CONCLUSIONS: Our study suggests that visceral manipulation in addition to
      standard care is not effective in changing short-term outcomes but may produce
      clinically worthwhile improvements in pain at 1 year.

PMID- 25378097
TI  - Evaporation-induced transition from Nepenthes pitcher-inspired slippery surfaces
      to lotus leaf-inspired superoleophobic surfaces.
AB  - The newly developed Nepenthes pitcher (NP)-inspired slippery surfaces, formed by
      immobilizing fluoroliquids on lotus leaf (LL)-inspired superoleophobic surfaces,
      are of great general interest, whereas there are many interesting phenomena and
      fundamental scientific issues remaining to be unveiled. Here we present our
      findings of the effects of evaporation of the fluoroliquid, an inevitable process
      in most cases, -induced transition from NP-inspired to LL-inspired surfaces on
      the wettability, transparency, and self-cleaning property of the surfaces. The
      transition is controlled by regulating the evaporation temperature of the model
      fluoroliquid, Krytox100. The evaporation of Krytox100 has great a influence on
      the wettability, transparency, and self-cleaning property. An intermediate
      "sticky" state is observed in the transition process. We believe that our
      findings in the transition process are helpful in understanding the similarities
      and differences between the NP-inspired and LL-inspired surfaces and in designing
      new bioinspired antiwetting surfaces and exploring their potential applications. 

PMID- 25378098
TI  - Electron-driven self-assembly of salt nanocrystals in liquid helium.
AB  - The self-assembly of salt nanocrystals from chemical reactions inside liquid
      helium is reported for the first time. Reaction is initiated by an electron
      impacting a helium nanodroplet containing sodium atoms and SF6 molecules, leading
      to preferential production of energetically favorable structures based on the
      unit cell of crystalline NaF. These favorable structures are observed as magic
      number ions (anomalously intense peaks) in mass spectra and are seen in both
      cationic and anionic channels in mass spectra, for example, (NaF)n Na(+) and
      (NaF)n F(-) . In the case of anions the self-assembly is not directly initiated
      by electrons: the dominant process involves resonant electron-induced production
      of metastable electronically excited He(-) anions, which then initiate anionic
      chemistry by electron transfer. 

PMID- 25378099
TI  - Enantioselective degradation of chiral insecticide dinotefuran in greenhouse
      cucumber and soil.
AB  - The enantioselective degradation behavior of the chiral insecticide dinotefuran
      in cucumber and soil was investigated under greenhouse conditions based on the
      method established with a normal-phase high-performance chromatography (HPLC) on
      a ChromegaChiral CCA column (250 * 4.6 mm, 5 um, ES Industries). The linearity
      range, matrix effect, precision, and accuracy of the method were evaluated and
      the method was then successfully applied for the enantioselective analysis of
      dinotefuran in cucumber and soil. Significant enantioselectivity of degradation
      was observed in soil according to the results. The (+)-dinotefuran was more
      persistent in soil with half-life of 21.7 d, which is much longer than that of (
      )-dinotefuran (16.5 d). In cucumber, the (-)-dinotefuran also tended to be
      preferentially degraded both in foliar and douche treatment. However, the
      statistical analysis indicated the enantioselectivity of degradation in cucumber
      was not significant. The research provides the first report concerning the
      enantioselective degradation of dinotefuran enantiomers and the results can be
      used for understanding the insect-controlling effect and food safety evaluation.

PMID- 25378100
TI  - Neuroinvasive phlebovirus infection in Greece: a case report.
AB  - OBJECTIVE: Sandfly fever phleboviruses are endemic in Mediterranean countries. We
      report a febrile phlebovirus case in a Greek patient who presented signs of
      neuroinvasive infection. METHODS: In summer 2010, a 20-year-old male was admitted
      to hospital with fever and lethargy; he was a resident of central Macedonia,
      northern Greece, where a large outbreak of West Nile virus (WNV) infections
      occurred at that time. Since there was no laboratory evidence of WNV infection,
      the patient's serum and cerebrospinal fluid were tested for a probable
      phlebovirus infection. RESULTS: High titers of IgM and IgG antibodies against
      Toscana virus were detected in serum and cerebrospinal fluid, while the titers
      against sandfly fever Naples virus were lower; no reactivity was detected against
      sandfly Sicilian and Cyprus viruses. Since neutralization assays were not
      performed and PCR resulted in being negative, it was concluded that the causative
      agent was a phlebovirus of the sandfly fever Naples serocomplex. CONCLUSION: The
      present case confirms results from previous seroprevalence studies showing that
      phleboviruses of the sandfly fever Naples serocomplex are present in Greece and
      provides evidence that they cause febrile neuroinvasive disease in humans,
      prompting for inclusion of phleboviral infections in the differential diagnosis
      of acute febrile cases during the time when sandflies are active.

PMID- 25378101
TI  - A White Paper on the medical and social needs of people with epilepsy and
      intellectual disability: the Task Force on Intellectual Disabilities and Epilepsy
      of the International League Against Epilepsy.
AB  - This White Paper builds on the publication of the International League Against
      Epilepsy (ILAE) and International Bureau for Epilepsy (IBE) report "Listening for
      a change-medical and social needs of people with intellectual disability who have
      epilepsy" (Listening for a change the medical and social needs of people with
      epilepsy and intellectual disability, ILAE, 2013). The Paper presents an overview
      of the recommendations of the report, which aim to improve the health and social
      care of this important population of people with epilepsy worldwide. Actions in
      four domains are indicated: (1) the development of standards and initiatives that
      would enhance diagnosis, pathways to investigation, and treatment; (2) the
      development of guidelines for treatment, specifically best practice in the
      management of antiepileptic drugs including rescue medication; (3) the
      development of standards for primary care, multidisciplinary teamwork, and
      clinical consultations, with emphasis on the need to enhance communication and
      improve access to information; and (4) the enhancement of links among different
      stakeholders including medical services, educational establishments, employment
      services, organizations providing opportunities for social engagement, and family
      members. The breadth of needs of this population is a challenge to the epilepsy
      world, spanning all the professional groupings, care providers, and the research
      modalities in epilepsy. 

PMID- 25378103
TI  - RNA-Seq-based toxicogenomic assessment of fresh frozen and formalin-fixed tissues
      yields similar mechanistic insights.
AB  - Formalin-fixed, paraffin-embedded (FFPE) pathology specimens represent a
      potentially vast resource for transcriptomic-based biomarker discovery. We
      present here a comparison of results from a whole transcriptome RNA-Seq analysis
      of RNA extracted from fresh frozen and FFPE livers. The samples were derived from
      rats exposed to aflatoxin B1 (AFB1 ) and a corresponding set of control animals.
      Principal components analysis indicated that samples were separated in the two
      groups representing presence or absence of chemical exposure, both in fresh
      frozen and FFPE sample types. Sixty-five percent of the differentially expressed
      transcripts (AFB1 vs. controls) in fresh frozen samples were also differentially
      expressed in FFPE samples (overlap significance: P < 0.0001). Genomic signature
      and gene set analysis of AFB1 differentially expressed transcript lists indicated
      highly similar results between fresh frozen and FFPE at the level of chemogenomic
      signatures (i.e., single chemical/dose/duration elicited transcriptomic
      signatures), mechanistic and pathology signatures, biological processes,
      canonical pathways and transcription factor networks. Overall, our results
      suggest that similar hypotheses about the biological mechanism of toxicity would
      be formulated from fresh frozen and FFPE samples. These results indicate that
      phenotypically anchored archival specimens represent a potentially informative
      resource for signature-based biomarker discovery and mechanistic characterization
      of toxicity.

PMID- 25378102
TI  - Genomic identification and characterization of the pseudoautosomal region in
      highly differentiated avian sex chromosomes.
AB  - The molecular characteristics of the pseudoautosomal region (PAR) of sex
      chromosomes remain elusive. Despite significant genome-sequencing efforts, the
      PAR of highly differentiated avian sex chromosomes remains to be identified. Here
      we use linkage analysis together with whole-genome re-sequencing to uncover the
      630-kb PAR of an ecological model species, the collared flycatcher. The PAR
      contains 22 protein-coding genes and is GC rich. The genetic length is 64 cM in
      female meiosis, consistent with an obligate crossing-over event. Recombination is
      concentrated to a hotspot region, with an extreme rate of >700 cM/Mb in a 67-kb
      segment. We find no signatures of sexual antagonism and propose that sexual
      antagonism may have limited influence on PAR sequences when sex chromosomes are
      nearly fully differentiated and when a recombination hotspot region is located
      close to the PAR boundary. Our results demonstrate that a very small PAR suffices
      to ensure homologous recombination and proper segregation of sex chromosomes
      during meiosis. 

PMID- 25378105
TI  - Chordoid meningiomas: incidence and clinicopathological features of a case series
      over 18 years.
AB  - Chordoid meningioma (CM) is a rare subtype of meningioma, classified as grade II,
      which exhibits a high rate of recurrence following subtotal resection. We
      retrospectively examined nine cases of chordoid meningioma over a case series of
      1743 meningiomas (0.52%) operated upon at our institution from 1995 to 2013. All
      the reported clinicopathological findings were analyzed. Two hundred and twenty
      one CM cases have been published to date worldwide and few single-center large
      case series have been issued. Seventy-five percent of the cases that underwent
      subtotal resection at our institution had recurrence within 1 year. Total
      resection of the tumor should be the major objective of surgery to reduce the
      possibility of tumor recurrence. The percentage of chordoid features within the
      tumor specimen could assist in predicting the pathogenesis of the lesion. The
      correlation of the index of proliferation to recurrence rate is still
      controversial. Much debate exists with regard to the role of adjuvant
      radiotherapy in CM cases. Immunohistochemical, cytological and ultrastructural
      studies should be used in combination to assure a correct diagnosis of CM. Owing
      to the rare occurrence of this meningioma subtype, larger case series are
      required to assist in providing a reference for diagnosis and to improve the
      therapeutic management of CM.

PMID- 25378104
TI  - Genome-wide patterns of copy number variation in the diversified chicken genomes
      using next-generation sequencing.
AB  - BACKGROUND: Copy number variation (CNV) is important and widespread in the
      genome, and is a major cause of disease and phenotypic diversity. Herein, we
      performed a genome-wide CNV analysis in 12 diversified chicken genomes based on
      whole genome sequencing. RESULTS: A total of 8,840 CNV regions (CNVRs) covering
      98.2 Mb and representing 9.4% of the chicken genome were identified, ranging in
      size from 1.1 to 268.8 kb with an average of 11.1 kb. Sequencing-based
      predictions were confirmed at a high validation rate by two independent
      approaches, including array comparative genomic hybridization (aCGH) and
      quantitative PCR (qPCR). The Pearson's correlation coefficients between
      sequencing and aCGH results ranged from 0.435 to 0.755, and qPCR experiments
      revealed a positive validation rate of 91.71% and a false negative rate of
      22.43%. In total, 2,214 (25.0%) predicted CNVRs span 2,216 (36.4%) RefSeq genes
      associated with specific biological functions. Besides two previously reported
      copy number variable genes EDN3 and PRLR, we also found some promising genes with
      potential in phenotypic variation. Two genes, FZD6 and LIMS1, related to disease
      susceptibility/resistance are covered by CNVRs. The highly duplicated SOCS2 may
      lead to higher bone mineral density. Entire or partial duplication of some genes
      like POPDC3 may have great economic importance in poultry breeding. CONCLUSIONS:
      Our results based on extensive genetic diversity provide a more refined chicken
      CNV map and genome-wide gene copy number estimates, and warrant future CNV
      association studies for important traits in chickens.

PMID- 25378106
TI  - Device-based in vitro techniques for mechanical stimulation of vascular cells: a
      review.
AB  - The most common cause of death in the developed world is cardiovascular disease.
      For decades, this has provided a powerful motivation to study the effects of
      mechanical forces on vascular cells in a controlled setting, since these cells
      have been implicated in the development of disease. Early efforts in the 1970 s
      included the first use of a parallel-plate flow system to apply shear stress to
      endothelial cells (ECs) and the development of uniaxial substrate stretching
      techniques (Krueger et al., 1971, "An in Vitro Study of Flow Response by Cells,"
      J. Biomech., 4(1), pp. 31-36 and Meikle et al., 1979, "Rabbit Cranial Sutures in
      Vitro: A New Experimental Model for Studying the Response of Fibrous Joints to
      Mechanical Stress," Calcif. Tissue Int., 28(2), pp. 13-144). Since then, a
      multitude of in vitro devices have been designed and developed for mechanical
      stimulation of vascular cells and tissues in an effort to better understand their
      response to in vivo physiologic mechanical conditions. This article reviews the
      functional attributes of mechanical bioreactors developed in the 21st century,
      including their major advantages and disadvantages. Each of these systems has
      been categorized in terms of their primary loading modality: fluid shear stress
      (FSS), substrate distention, combined distention and fluid shear, or other
      applied forces. The goal of this article is to provide researchers with a survey
      of useful methodologies that can be adapted to studies in this area, and to
      clarify future possibilities for improved research methods. 

PMID- 25378107
TI  - Recent international trends in psychotropic medication prescriptions for children
      and adolescents.
AB  - Prescriptions of psychotropic medications have become an important intervention
      for many children and adolescents with mental disorders, and the rise of these
      prescriptions is debated intensively both among experts and the public. This
      review reports some recent international findings on point prevalence rates,
      cross-country comparisons, and time trends in psychotropic medication
      prescriptions for children and adolescents. Besides the total prescription rates,
      figures for antidepressants, antipsychotics, stimulants, and anxiolytics
      prescriptions are provided. The overall prescription rates of psychotropics in
      general and the major medication subgroups prescribed to children and adolescents
      vary substantially between countries with the US consumption being markedly
      higher than the use in European countries. However, even among the latter there
      are marked variations in findings. Studies reporting on time trends clearly
      indicate that there was a marked increase in the use of psychotropics for
      children and adolescents in the recent past. However, only a single study
      adjusted prevalence rates for the increasing number of children and adolescents
      assessed and treated in institutions providing mental health care. Considering
      the increasing numbers of children and adolescents seen in psychiatric services,
      the increase of psychotropic medications is less strong though still pronounced
      enough to stimulate further reflections on the use of these interventions. 

PMID- 25378108
TI  - Giant pituitary adenoma.

PMID- 25378109
TI  - Muscle strength measurements and functional outcome of an untreated complete
      distal rectus femoris muscle tear.
AB  - A 46-year-old man sustained an injury to his right thigh while skiing. He sought
      medical advice after 6 weeks, presenting a palpable painful mass of his anterior
      proximal thigh but no functional deficit. An isolated complete distal
      intrasubstance tear of the rectus femoris muscle was diagnosed on ultrasound and
      MRI scans, and the patient received no medical treatment. Functional and
      dynamometer tests after 1 year showed high limb symmetry indexes and only
      slightly reduced values for peak torque and total work on the injured side. The
      patient had resumed skiing activities and reported slight pain after intense
      downhill skiing runs, but no functional limitations. MRI scans after 19 months
      showed increased retraction of the rectus femoris muscle. The natural history of
      an untreated complete distal rectus femoris muscle tear with no functional
      deficit may result in minimal disability.

PMID- 25378110
TI  - Is the use of high frequency oscillatory ventilator beneficial in managing severe
      chest injury with massive air leak?
AB  - Severe thoracic trauma can be associated with immediate life-threatening injuries
      including major air leak syndrome that can lead to acute respiratory failure and
      refractory hypoxaemia. Such injuries invariably require thoracotomy following
      failure of conventional ventilation strategy and paucity of other non-operative
      interventions. We describe a case in which we used high frequency oscillatory
      ventilation (HFOV) as a part of management of such injury and averted the need
      for thoracotomy. 

PMID- 25378111
TI  - High-dose tigecycline and colistin for successful treatment of disseminated
      carbapenem-resistant Klebsiella pneumoniae infection in a liver transplant
      recipient.
AB  - Solid organ transplantation (SOT) is a risk factor for the acquisition of
      carbapenem-resistant Klebsiella pneumoniae. This infection is associated with a
      high mortality rate given the limited armamentarium of antibiotics for multidrug
      resistant organisms along with continued immunosuppression to prevent graft
      rejection. We report a case of carbapenem-resistant K. pneumoniae pneumonia,
      bacteraemia and intra-abdominal infection in a newly transplanted liver
      recipient. The patient was successfully treated with a long course of high-dose
      tigecycline and colistin, along with surgical drainage. We discuss SOT-relevant
      epidemiology, therapeutic options and the rationale for our treatment choice. 

PMID- 25378112
TI  - Doubling back of Foley catheter in urethra in a tetraplegic patient: delayed
      recognition.
AB  - A 51-year-old man with C-6 tetraplegia had ureteric calculi, developed ureteric
      stricture and required bilateral nephrostomy. Following change of the left
      nephrostomy, bloody urine was drained per nephrostomy. The urethral catheter was
      also changed; bloody drainage per urethral catheter was attributed to blood
      seeping from the left kidney. The length of the Foley catheter outside the penis
      appeared correct; therefore, it was presumed that the catheter had been
      introduced into the bladder. The following day, bladder washout could not be
      performed due to blockage of the catheter. CT of the kidneys and bladder revealed
      doubling back of the Foley catheter in the bulbar urethra with the balloon
      inflated in the urethra. The urethral catheter was removed and another catheter
      inserted satisfactorily by a senior doctor. From this experience we learned that
      a 'Long Catheter Sign' will not be positive if the catheter doubles back in the
      urethra. When in doubt, imaging studies should be performed immediately to check
      the position of the Foley catheter. 

PMID- 25378113
TI  - Subcutaneous nodules as the presenting symptom of diffuse large B cell lymphoma.

PMID- 25378114
TI  - Negative urine pregnancy test in a molar pregnancy: is it possible?
AB  - A urine pregnancy test is commonly used to detect pregnancy and is based on
      finding intact beta-human chorionic gonadotrophin (hCG) molecules in the urine by
      an immunoassay system. However, the significantly large amount of beta-hCG in
      molar pregnancy may paradoxically lead to a false-negative result due to a
      phenomenon known as the 'high dose hook effect'. A case of molar pregnancy with
      negative urine pregnancy test but very high serum beta-hCG is reported. Every
      obstetrician should be aware of this limitation in the presence of a high index
      of suspicion of gestational trophoblastic disease but negative urine pregnancy
      test. 

PMID- 25378115
TI  - Paraneoplastic vertigo as the presenting symptom of a testicular seminoma.
AB  - Vertigo is a common presenting symptom, but rarely may be caused by a malignancy.
      We present a case of a 44-year-old man who presented with nystagmus and vertigo
      precipitated by movement, with accompanying nausea and weight loss. Diagnostic
      workup revealed a right testicular mass that was resected and found to be a
      seminoma. The patient's symptoms resolved after surgical resection and treatment
      with corticosteroids. 

PMID- 25378116
TI  - Unusual contents of a large incarcerated inguinal hernia.

PMID- 25378117
TI  - Immunoglobulin E antibodies to atracurium: a new diagnostic tool?

PMID- 25378118
TI  - Development of a measure for maternal confidence in knowledge and understanding
      and examination of psychosocial influences at the time of a child's heart
      surgery.
AB  - PURPOSE: The purpose was to develop a maternal confidence in knowledge and
      understanding scale (Maternal Knowledge and Understanding Scale [MKUS]) and
      examine the effect of psychosocial factors at the time of a child's heart
      surgery. DESIGN AND METHODS: Using cross-sectional design, the MKUS was developed
      and tested. Validated instruments were used to examine the impact of psychosocial
      factors. RESULTS: The MKUS showed acceptable internal consistency (Cronbach's
      alpha .78). Higher levels of maternal anxiety and lower levels of social support
      were associated with lower MKUS scores (p < .05). PRACTICE IMPLICATIONS: A
      measure of maternal confidence in knowledge and understanding could draw
      attention to psychosocial factors and opportunities to enhance nursing support.

PMID- 25378119
TI  - Work-related stress in midlife is associated with higher number of mobility
      limitation in older age-results from the FLAME study.
AB  - The aim of this study is to investigate whether work-related stress symptoms in
      midlife are associated with a number of mobility limitations during three decades
      from midlife to late life. Data for the study come from the Finnish Longitudinal
      Study of Municipal Employees (FLAME). The study includes a total of 5429 public
      sector employees aged 44-58 years at baseline who had information available on
      work-related stress symptoms in 1981 and 1985 and mobility limitation score
      during the subsequent 28-year follow-up. Four midlife work-related stress
      profiles were identified: negative reactions to work and depressiveness,
      perceived decrease in cognition, sleep disturbances, and somatic symptoms. People
      with a high number of stress symptoms in 1981 and 1985 were categorized as having
      constant stress. The number of self-reported mobility limitations was computed
      based on an eight-item list of mobility tasks presented to the participants in
      1992, 1997, and 2009. Data were analyzed using joint Poisson regression models.
      The study showed that depending on the stress profile, persons suffering from
      constant stress in midlife had a higher risk of 30-70 % for having one more
      mobility limitation during the following 28 years compared to persons without
      stress after adjusting for mortality, several lifestyle factors, and chronic
      conditions. A less pronounced risk increase (20-40 %) was observed for persons
      with occasional symptoms. The study suggests that effective interventions aiming
      to reduce work-related stress should focus on both primary and secondary
      prevention. 

PMID- 25378120
TI  - Volatiles emitted from tea plants infested by Ectropis obliqua larvae are
      attractive to conspecific moths.
AB  - Herbivore-induced plant volatiles have been reported to play a role in the host
      searching behavior of herbivores. However, next to nothing is known about the
      effect of volatiles emitted from tea plants infested by Ectropis obliqua larvae
      on the behavior of conspecific adults. Here, we found that tea plants infested by
      E. obliqua caterpillars for 24 h were more attractive to both virgin male and
      female E. obliqua adults than were intact, uninfested tea plants; moreover, mated
      female E. obliqua moths were more attracted by infested tea plants and
      preferentially oviposited on these plants, whereas male moths were repelled by
      infested plants once they had mated. Volatile analysis revealed that the
      herbivore infestation dramatically increased the emission of volatiles. Among
      these volatiles, 17 compounds elicited antennal responses from both male and
      female virginal moths. Using a Y-tube olfactometer, we found that 3 of the 17
      chemicals, benzyl alcohol, (Z)-3-hexenyl hexanoate, and (Z)-3-hexenal, were
      attractive, but two compounds, linalool and benzyl nitril, were repellent to
      virgin male and female moths. One chemical, (Z)-3-hexenyl acetate, was attractive
      only to virgin males. Mated females were attracted by three compounds, (Z)-3
      hexenyl hexanoate, (Z)-3-hexenyl acetate, and (Z)-3-hexenal; whereas mated males
      were repelled by (Z)-3-hexenol. The findings provide new insights into the
      interaction between tea plants and the herbivores, and may help scientists
      develop new measures with which to control E. obliqua. 

PMID- 25378121
TI  - Influence of the pathogen Candidatus Liberibacter solanacearum on tomato host
      plant volatiles and psyllid vector settlement.
AB  - Candidatus Liberibacter solanacearum (CLso) is an unculturable bacterium vectored
      by the tomato potato psyllid (TPP) Bactericera cockerelli and has been associated
      with Zebra chip disease in potato and with other economically relevant symptoms
      observed in solanaceous crops. By altering their host and vector's biological
      system, pathogens are able to induce changes that benefit them by increasing
      their transmission rate. Understanding these changes can enable better targeting
      of mechanisms to control pathogen outbreaks. Here, we explored how the CLso
      infectious status affects the volatile organic compounds (VOCs) of the tomato
      plant, and whether the CLso infectious status of TPP influences host plant
      settlement. These chemical and behavioral changes can ultimately affect the rate
      of encounter between the host and the vector. Results from headspace volatile
      collection of tomato plants showed that CLso infected tomato plants emitted a
      qualitatively and quantitatively different blend of VOCs compared to sham
      infected plants. By a factorial experiment, we showed that CLso negative (CLso-)
      TPP preferred to settle 70 % more often on infected tomato plants, while CLso
      positive (CLso+) TPP were found 68 % more often on sham-infected tomato plants.
      These results provide new evidence in favor of both host and vector manipulation
      by CLso.

PMID- 25378122
TI  - Evaluation of endometrial thickness and bone mineral density based on CYP2D6
      polymorphisms in Turkish breast cancer patients receiving tamoxifen treatment.
AB  - BACKGROUND: Several previous studies have examined the effect of CYP2D6 gene
      polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva,
      Nolvadex) in the treatment of breast cancer. In the present study, the metabolic
      profiles associated with various CYP2D6 genotypes were evaluated. METHOD: In the
      present study 92 Turkish breast cancer patients with early-stage hormone receptor
      positive tumors treated with adjuvant tamoxifen (20 mg) were evaluated for CYP2D6
      genotype and metabolic profiles. Known side effects of tamoxifen treatment,
      including endometrial thickening, changes in serum lipid levels and bone density,
      and hepatosteatosis, were evaluated according to the CYP2D6 polymorphism. RESULT:
      The distribution of metabolic characteristics in the Turkish population was as
      follows: 77.1% normal metabolism, 11.5% intermediate metabolism, 5.2% ultrarapid
      metabolism, and 2.1% poor metabolism. The CYP2D6 genotypes associated with rapid
      metabolism were CYP2D6 3X*1/*1 duplication (DUP) and CYP2D6 2X*1/*2, while poor
      metabolism was associated with the genotypes CYP2D6 *3/*4 and CYP2D6 *6/*6. There
      was no statistically significant relationship between metabolic characteristics
      and bone density or hepatosteatosis. A statistically significant difference in
      total cholesterol and triglycerides was detected in lipid profile analysis (p =
      0.003, p = 0.02). Assessment of endometrial thickness revealed a significant
      association of hyperplasia and poor metabolism, and an association between
      atrophy and ultrarapid metabolism (p = 0.01). CONCLUSION: Significant development
      of endometrial hyperplasia was identified among individuals with poor tamoxifen
      metabolism. As a result, tamoxifen may be a significant predictor of endometrial
      thickening among individuals with poor metabolic characteristics.

PMID- 25378123
TI  - Transformed nodal marginal zone lymphoma versus diffuse large B cell lymphoma:
      the microRNA aspect.

PMID- 25378124
TI  - Salinity-induced noise in membrane potential of Characeae Chara australis: effect
      of exogenous melatonin.
AB  - Salt sensitive Characeae Chara australis responds to 50 mM NaCl by a prompt
      appearance of noise in the trans-membrane potential difference (PD). The noise
      diminishes with time in saline and PD depolarization, leading to altered current
      voltage characteristics that could be modeled with H(+)/OH(-) channels. Beilby
      and Al Khazaaly (JMB 230:21-34, 2009) suggested that the noise might arise from
      cooperative transient opening of H(+)/OH(-) channels. Presoaking cells in 10 MUM
      melatonin over 24 h abolished the noise in some cells, postponed its appearance
      in others or changed its characteristics. As melatonin is a very effective
      antioxidant, we postulated opening of H(+)/OH(-) channels by reactive oxygen
      species (ROS). Measurement of ROS using dihydrodichlorofluorescein diacetate
      confirmed substantial reduction in ROS production in melatonin-treated cells in
      saline and sorbitol media. However, ROS concentration decreased as a function of
      time in saline medium. Possible schemes for activation of H(+)/OH(-) channels
      under salinity stress are considered.

PMID- 25378126
TI  - Risk assessment in travel medicine: how to obtain, interpret, and use risk data
      for informing pre-travel advice.
AB  - BACKGROUND: It has been recommended that numerical risk data should be provided
      during the pre-travel consultation in order for travelers to make informed
      decisions regarding uptake of preventive interventions. METHODS: In this article,
      we review the definitions of the various risk measures, particularly as they
      relate to travel health, and discuss the study designs and methodological details
      required to obtain each measure. RESULTS: Risk measures can be broadly divided
      into absolute risk measures (including incidence rate, attack rate, and incidence
      density) and risk factor measures (including relative risk, risk ratio, and odds
      ratio). Although there are limitations inherent to each measure, absolute risk
      measures estimate the baseline risk for an "average" traveler, and risk factor
      measures help determine whether the risks for an individual traveler are likely
      to be higher or lower than this average, which is determined by specific traveler
      and itinerary characteristics. Incremental risk considerations add additional
      complexity, and risk communication plus risk perception/risk tolerance have
      additional impact on the individual traveler's interpretation of risk measures.
      CONCLUSIONS: Travel health practitioners should be aware of the complexities,
      limitations, and difficulties in understanding numerical risk data, as these
      factors are important in travelers' acceptance or rejection of interventions
      offered.

PMID- 25378125
TI  - Ciprofloxacin metalloantibiotic: an effective antibiotic with an influx route
      strongly dependent on lipid interaction?
AB  - Fluoroquinolones are antibiotics that have a large spectrum of action against
      bacteria, especially Gram-negative. A strategy to enhance their pharmacological
      behavior, and try to counteract bacterial resistance, is their coordination to
      divalent metal ions and 1,10-phenanthroline. These stable complexes modify
      fluoroquinolones potency and specificity, possibly due to their alternative
      translocation through the bacterial membranes. In this work, we determined the
      interaction of ciprofloxacin and its copper(II) ternary complex with unilamellar
      liposomes of DMPC, POPE/POPG (0.75:0.25), POPE/POPG/cardiolipin (0.67:0.23:0.10),
      and E. coli total extract, using time-resolved and steady-state fluorescence
      spectroscopy. The association constants determined show that the interaction of
      both compounds depends on membrane lipids composition and is always higher for
      the metalloantibiotic, a trend already observed for other fluoroquinolone
      metalloantibiotics. Nevertheless, the interaction of ciprofloxacin
      metalloantibiotic is, normally, higher, which reflects the fluoroquinolone
      species that are present in solution at physiological pH. In overall, the results
      obtained suggest that ciprofloxacin and its metalloantibiotic have different
      translocation pathways, proposing that the diffusion of the metalloantibiotic is
      a hydrophobic mechanism and suggesting that this new metalloantibiotic may be a
      good choice to replace the pure ciprofloxacin and bypass, at least, one of the
      mechanisms of the bacterial resistance to fluoroquinolones. 

PMID- 25378127
TI  - U.S. Military Discharges and Pre-existing Personality Disorders: A Health Policy
      Review.
AB  - The Department of Defense (DoD) is facing allegations service members were
      wrongfully discharged for pre-existing personality disorders. From 2001 to 2007,
      26,000 enlisted service members were discharged for a pre-existing personality
      disorder (2.6 % of total discharges). With national media attention of the issue,
      personality disorder discharges were reduced by 31 % in 2008 with new discharge
      procedures issued by the DoD. Even with the reduction, a government review found
      the DoD did not adhere to its discharge protocols. The objective of this paper is
      to explore personality disorders in the military, analyze various costs to
      stakeholders, and identify potential policy alternatives.

PMID- 25378128
TI  - Adenotonsillectomy reduces acute asthma exacerbations in children, study shows.

PMID- 25378129
TI  - Caring until the end: a systematic literature review exploring Paediatric
      Intensive Care Unit end-of-life care.
AB  - AIMS AND OBJECTIVES: A systematic review of the literature focusing on the
      provision of end-of-life care (EOLC) on Paediatric Intensive Care Units (PICUs)
      and the options available to children and families within contemporary clinical
      practice. BACKGROUND: The death of a child is recognized as a uniquely traumatic
      experience for a parent. The care delivered to a child and family surrounding
      death can have a lasting effect on the grieving process. The majority of
      paediatric deaths occur within PICUs, often as a result of withdrawing or
      withholding treatment. Withdrawal of intensive care is becoming more common
      within UK PICUs, and this review will focus on the options available when a
      child's on-going treatment is deemed to be futile. SEARCH STRATEGIES: Literature
      published from 2002 to 2013 was obtained from a range of sources and critically
      reviewed. Cormack's (2000) framework for systematic literature review was
      utilized to critically review literature before analysis and synthesis of the
      literature was undertaken within the qualitative approach. INCLUSION/EXCLUSION
      CRITERIA: Each article focused on issues surrounding the topic area, excluded
      adult and neonatal intensive care and was published in English. CONCLUSIONS:
      Eight papers met the inclusion criteria and were suitable for review
      (highlighting difficulties in reviewing a small, complex subject area). Key
      themes identified included family views, staff views, decision-making, medico
      legal issues and resources. RELEVANCE TO CLINICAL PRACTICE: Although the number
      of relevant articles is limited, a wide range of challenges facing children,
      parents and staff are highlighted, whilst generally supporting the facilitation
      of transferring children to their homes or hospice for withdrawal of intensive
      care and continuing EOLC. Further research is required, particularly regarding
      long-term implications, legal issues and the effectiveness of clinical protocols.

PMID- 25378130
TI  - [Retinoblastoma in Kenya: survival and prognostic factors].
AB  - BACKGROUND: In industrialized nations a curative therapy of retinoblastoma can be
      achieved in a large number of patients due to timely diagnosis and therapy. In
      developing countries the survival rates are much lower and very little data have
      been published especially from Africa. OBJECTIVES: This study was performed to
      investigate the survival and prognostic factors of retinoblastoma patients
      admitted to Kenyatta National Hospital, the national referral hospital in Kenya.
      MATERIAL AND METHODS: In this study all records of patients admitted with
      retinoblastoma from January 2000 to December 2004 were reviewed. Demographic
      data, clinical presentation, intraoperative findings and histology reports were
      recorded and the patients or their relatives were contacted during follow-up to
      investigate the outcome and survival. RESULTS: Files of 160 patients (86 males
      and 74 females) were retrieved for this study. Data on 3-year survival could be
      acquired from 105 patients and the cumulative 3-year survival rate was 26.6 %.
      Factors significantly influencing survival were age at presentation less than 12
      months, early disease at presentation (leukocoria only), no extraocular growth
      and total delay of management <= 5 months. Proptosis and tumor recurrence were
      associated with a 3-year mortality of 100 %. CONCLUSION: The main reasons for
      poor outcome were late presentation and recurrent disease after initial treatment
      elsewhere, extraocular growth and delay between initial presentation and
      treatment. Awareness of the public and of healthcare workers should be increased
      in order to reduce the time delay until diagnosis and treatment.

PMID- 25378131
TI  - [Vitreous hemorrhage of unusual genesis].

PMID- 25378132
TI  - [Case numbers and revenues of main and affiliated ophthalmological departments:
      Developments since 2005].
AB  - BACKGROUND: Currently, very little data exist on the development of healthcare
      related and financial parameters of both types of inpatient treatment: clinical
      units run by affiliated physicians and those run by hospital physicians. AIM:
      This study used a methodology based on published secondary data to estimate the
      annual number of cases and revenues for in inpatient ophthalmological treatment
      differentiated into clinical units run by affiliated physicians and those run by
      hospital physicians. MATERIAL AND METHODS: The case-based flat-rate catalogs and
      accompanying research data published annually by the Institute for the Hospital
      Remuneration System (Institut fur Entgeltsysteme im Krankenhaus, InEK) served as
      a data source. The numbers of annual cases according to major diagnostic
      categories (MDC) and diagnosis-related groups (DRG), stratified by the unit type
      are reported for the period 2005-2012. The cumulative total revenues were
      calculated based on the number of ophthalmological cases, the effective DRG cost
      weighting, the length of stay and the national basic case values. RESULTS:
      Between 2005 and 2012 the units run by affiliated physicians showed a contrasting
      trend to those run by hospital physicians: the number of cases in units run by
      hospital physicians increased by  14 %, while those in units run by affiliated
      physicians decreased by  6 %. Up to 2012 the effective cost weighting for cases
      in units run by hospital physicians decreased to 0.60 (- 3 %) and increased to
      0.43 (+ 5 %) for units run by affiliated physicians. In 2012 the corresponding
      effective case revenue accounted for 1767 euros and 1271 euros, respectively.
      Total revenue estimates for all inpatient ophthalmological treatment increased
      from 549 million euros in 2005 to 630 million euros in 2012, while the share of
      units run by affiliated physicians amounted to 10.6 % and 9.7 %, respectively.
      CONCLUSION: According to the indicators "number of cases" and "total revenue",
      the affiliated ophthalmologists lost ground compared with inpatient units run by
      hospital physicians over the period from 2005-2012.

PMID- 25378133
TI  - Off-target assessment of CRISPR-Cas9 guiding RNAs in human iPS and mouse ES
      cells.
AB  - The CRISPR-Cas9 system consists of a site-specific, targetable DNA nuclease that
      holds great potential in gene editing and genome-wide screening applications. To
      apply the CRISPR-Cas9 system to these assays successfully, the rate at which Cas9
      induces DNA breaks at undesired loci must be understood. We characterized the
      rate of Cas9 off-target activity in typical Cas9 experiments in two human and one
      mouse cell lines. We analyzed the Cas9 cutting activity of 12 gRNAs in both their
      targeted sites and ~90 predicted off-target sites per gRNA. In a Cas9-based
      knockout experiment, gRNAs induced detectable Cas9 cutting activity in all on
      target sites and in only a few off-target sites genome-wide in human 293FT, human
      induced pluripotent stem (hiPS) cells, and mouse embryonic stem (ES) cells. Both
      the cutting rates and DNA repair patterns were highly correlated between the two
      human cell lines in both on-target and off-target sites. In clonal Cas9 cutting
      analysis in mouse ES cells, biallelic Cas9 cutting was observed with low off
      target activity. Our results show that off-target activity of Cas9 is low and
      predictable by the degree of sequence identity between the gRNA and a potential
      off-target site. Off-target Cas9 activity can be minimized by selecting gRNAs
      with few off-target sites of near complementarity.

PMID- 25378134
TI  - The role of clinical nurse specialists in the implementation and sustainability
      of a practice change.
AB  - AIM: This project's purpose was to promote and sustain a practice change focusing
      on delirium utilising the clinical nurse specialist (CNS) in a leadership role.
      BACKGROUND: Delirium is an altered state of consciousness accompanied by an acute
      change in cognition that tends to have a fluctuating course. Delirium is strongly
      associated with negative outcomes and is often unrecognised. METHOD: A policy was
      implemented stating that the RNs will screen patients for delirium with the
      confusion assessment method (CAM). Interdisciplinary delirium education was
      offered prior to the practice change and repeated at 3, 6 and 12 months after
      implementation. The documentation, completion and CAM accuracy screening were
      determined by the CNS. RESULTS: The CAM documentation and completion audit goal
      was met and sustained by week 21, and screenings were accurate 83% of the time.
      CONCLUSIONS: The CNS has an opportunity to take a leadership role when
      instituting an innovative practice change. Successful implementation of a new
      practice requires that patient care units are divided into cohorts with
      systematic roll-out of the initiative. IMPLICATIONS FOR NURSING MANAGEMENT: In
      addition to leadership, CNS availability on the patient care units is imperative
      to staff acceptance and sustainability of a practice change.

PMID- 25378135
TI  - Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in
      healthy horses.
AB  - The objectives of this study were to compare the pharmacokinetics and COX
      selectivity of three commercially available formulations of firocoxib in the
      horse. Six healthy adult horses were administered a single dose of 57 mg
      intravenous, oral paste or oral tablet firocoxib in a three-way, randomized,
      crossover design. Blood was collected at predetermined times for PGE2 and TXB2
      concentrations, as well as plasma drug concentrations. Similar to other reports,
      firocoxib exhibited a long elimination half-life (31.07 +/- 10.64 h), a large
      volume of distribution (1.81 +/- 0.59L/kg), and a slow clearance (42.61 +/- 11.28
      mL/h/kg). Comparison of the oral formulations revealed a higher Cmax , shorter
      Tmax , and greater AUC for the paste compared to the tablet. Bioavailability was
      112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE2
      was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and
      46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC50
      of approximately 27 ng/mL and an IC80 of 108 ng/ mL for COX2 inhibition.
      Inhibition of TXB2 production was not detected. This study indicates a lack of
      bioequivalence between the oral formulations of firocoxib when administered as a
      single dose to healthy horses.

PMID- 25378136
TI  - New aspects of the structure and mode of action of the human cathelicidin LL-37
      revealed by the intrinsic probe p-cyanophenylalanine.
AB  - The human cathelicidin peptide LL-37 is an important effector of our innate
      immune system and contributes to host defence with direct antimicrobial activity
      and immunomodulatory properties, and by stimulating wound healing. Its sequence
      has evolved to confer specific structural characteristics that strongly affect
      these biological activities, and differentiate it from orthologues of other
      primate species. In the present paper we report a detailed study of the folding
      and self-assembly of this peptide in comparison with rhesus monkey peptide RL-37,
      taking into account the different stages of its trajectory from bulk solution to
      contact with, and insertion into, biological membranes. Phenylalanine residues in
      different positions throughout the native sequences of LL-37 and RL-37 were
      systematically replaced with the non-invasive fluorescent and IR probe p
      cyanophenylalanine. Steady-state and time-resolved fluorescence studies showed
      that LL-37, in contrast to RL-37, forms oligomers with a loose hydrophobic core
      in physiological solutions, which persist in the presence of biological
      membranes. Fourier transform IR and surface plasmon resonance studies also
      indicated different modes of interaction for LL-37 and RL-37 with anionic and
      neutral membranes. This correlated with a distinctly different mode of bacterial
      membrane permeabilization, as determined using a flow cytometric method involving
      impermeant fluorescent dyes linked to polymers of defined sizes. 

PMID- 25378137
TI  - Using the mouse grimace scale to assess pain associated with routine ear notching
      and the effect of analgesia in laboratory mice.
AB  - Social housing is recommended where possible for laboratory mice. In order to
      achieve this, mice must be individually identifiable. Although, various methods
      are available, permanent identification is often required, such as ear notching.
      This method is likely to be painful and to date there is limited literature on
      pain assessment and alleviation for this routine husbandry practice. Here we
      aimed to determine if the mouse grimace scale (MGS) could be used to assess pain
      in C57BL/6 mice following routine ear notching. Langford et al. found that very
      acute noxious stimuli (i.e. < 10 min in duration) did not produce a change in MGS
      score in comparison to baseline. Here, no significant difference was found
      between MGS scores at baseline and immediately post ear notching, potentially
      indicating that the pain associated with ear notching is either too acute to
      assess using the MGS tool or the practice is not painful. Studies in other
      species indicate that ear notching is painful, therefore, unless we can
      confidently conclude that the process of ear notching is not painful, we should
      err on the side of caution and assume it is painful due to the large number of
      mice ear-notched and potential welfare consequences. Alternative methods of
      assessing pain following this routine practice should be used in order to assess
      both the potential pain in mice, and the effectiveness of analgesics or local
      anaesthetics to relieve any associated pain.

PMID- 25378138
TI  - A comparison of two common bile duct ligation methods to establish
      hepatopulmonary syndrome animal models.
AB  - The major drawback of the current common bile duct ligation (CBDL)-induced
      hepatopulmonary syndrome (HPS) animal model is the extremely high mortality rate
      that hinders experimental studies. The purpose of this study was to investigate
      an improved method of CBDL with the goal of developing a simple and reproducible
      rat HPS model after a single CBDL treatment. Two groups of male Sprague-Dawley
      rats underwent separate methods of CBDL: (1) the upper common bile duct ligation
      (UCBDL) group (n = 40), in which the first ligature was made near the junction of
      the hepatic ducts, and the second ligature was made above the entrance of the
      pancreatic duct; (2) the middle of the common bile duct ligation (MCBDL) group (n
      = 40), in which the first ligature was made in the middle of the common bile
      duct, and the second ligature was made above the entrance of the pancreatic duct.
      The CBDL-induced HPS rats were evaluated by pulse oximeter, arterial blood
      analysis, histopathology, and cerebral uptake of intravenous technetium-99m
      labeled albumin macroaggregates (which reflects intrapulmonary vascular
      dilation). The mortality rates of the UCBDL group and the MCBDL group were 42.5%
      and 77.5%, respectively (P < 0.05). These results suggest that the UCBDL, a
      single improved procedure, provides a better method compared to the established
      HPS model, because of the relatively high success rate and the decreased risk of
      complications. 

PMID- 25378139
TI  - The effect of midazolam on the recovery quality, recovery time and the minimum
      alveolar concentration for extubation in the isoflurane-anesthetized pig.
AB  - There are no reported studies evaluating the effect of midazolam on recovery
      quality, recovery time or minimum alveolar concentration (MAC) at which
      extubation occurs (MAC extubation). Our hypotheses were that midazolam
      administered prior to recovery would decrease MAC extubation, prolong recovery
      time but provide a smoother recovery. Sixteen Yorkshire pigs were anesthetized
      with isoflurane for approximately 5 h. The end-tidal isoflurane concentration was
      then stabilized at 1.4% for 20 min. Pigs were randomly assigned to receive
      midazolam or saline. The vaporizer was decreased by 10% every 10 min until
      extubation. Pigs were declared awake by a blinded observer and were assigned a
      recovery score by the same observer. Mean MAC extubation was not significantly
      different for pigs receiving saline prior to recovery compared with those pigs
      receiving midazolam. The overall mean MAC extubation for both groups was 0.6 +/-
      0.4 vol%. Time to extubation was not significantly longer with midazolam (124 +/-
      36 min) compared with the saline group (96 +/- 61 min; P = 0.09). Recovery score
      was not significantly different between groups (midazolam, 0.86 +/- 1.1; saline
      0.5 +/- 0.5; P = 0.26). In conclusion, midazolam did not affect MAC extubation.
      There was no advantage of administering midazolam in the recovery period when
      performing step-down titration of isoflurane anesthesia.

PMID- 25378140
TI  - Electronic effects of ligand substitution on metal-organic framework
      photocatalysts: the case study of UiO-66.
AB  - UiO-66-X (X = H, NH2, NO2, Br) have been successfully synthesized and tested for
      their photocatalytic activity in water treatment. Results show that electronic
      effect of the ligand substituents greatly affects the photocatalytic activity of
      UiO-66. The rates obtained by different substituents are linearly correlated with
      their Hammett coefficients. 

PMID- 25378142
TI  - Changing patterns of antigen exposure and their impact on the prevalence of
      allergy.
AB  - Industrial development has advanced at a varying pace in different parts of the
      world over the past 200 years. Inhabitants of the most industrially advanced
      regions have experienced major changes in patterns of antigen exposure to
      infectious agents and to environmental biologic substances. This article analyzes
      the major factors that affect the amounts and variety of antigens to which the
      immune system of a young child is exposed. Depending on individual living
      environments and lifestyles, the types of antigen exposure of young children are
      graded into five patterns: 'primitive', 'pre-modern', 'early modern', 'modern',
      and 'ultramodern'. These patterns represent increasing deviation from the pattern
      of human immune system exposure to antigens prior to the industrial revolution.
      This article further discusses how such changes in antigen exposure have affected
      the immunologic system, especially with regard to the development of total IgE
      and allergic response-relevant antigen-specific IgE, and how the patterns of
      antigen exposure are related to the propensity to develop allergy.

PMID- 25378143
TI  - Inhibition of osteosarcoma cell progression by MacroH2A via the downregulation of
      cyclin D and cyclin-dependent kinase genes.
AB  - MacroH2A is a histone modification factor the activity of which has been acutely
      studied in cancer progression, and a number of studies have shown that the
      progression of certain types of cancer is under regulation by MacroH2A. However,
      information regarding the underlying molecular mechanisms of MacroH2A inhibition
      on the cell cycle remains elusive, and elucidating this process may aid in the
      production of novel treatment strategies. The aim of the current study was to
      investigate the inhibitory effects of MacroH2A on osteosarcoma cell progression,
      and the possible molecular mechanisms of this process. MacroH2A overexpression
      and interference vectors were designed and transfected into U2-OS osteosarcoma
      cells. The cells underwent reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR), western blot analysis and immunofluorescence assays. The
      apoptosis rate and cell cycle stage were assayed using flow cytometry. The
      results revealed that the overexpression of MacroH2A inhibited the progression of
      U2-OS osteosarcoma cells, and the cells were arrested at the G2/M stage of the
      cell cycle. The molecular mechanism by which MacroH2A suppresses the cell
      progression involves the inhibition of the expression of cyclin D and cyclin
      dependent kinase (CDK) genes, including cyclin D1, cyclin D2, CDK4, CDK6 and
      CDK8. Taken together, the present results revealed that MacroH2A is an important
      modifier of chromatin that downregulates the progression of osteosarcoma cells
      and triggers disturbance of the cell cycle via the downregulation of cyclin D and
      CDK genes.

PMID- 25378144
TI  - Trifluoromethanesulfonyloxy-group-directed regioselective (3 + 2) cycloadditions
      of benzynes for the synthesis of functionalized benzo-fused heterocycles.
AB  - Highly regioselective (3 + 2) cycloadditions of
      (trifluoromethanesulfonyloxy)benzynes [(triflyloxy)benzynes] with 1,3-dipoles
      followed by cross-coupling reactions provided multisubstituted benzo-fused
      heterocycles. The triflyloxy group at the 3-position of benzynes, and even that
      at the remote 4-position, greatly affected the regiocontrol of the cycloaddition.
      These groups also served to install other substituents at their ipso-positions. 

PMID- 25378145
TI  - Near infrared spectroscopy is suitable for the classification of hazelnuts
      according to Protected Designation of Origin.
AB  - BACKGROUND: This study investigates the possibility of using near infrared
      spectroscopy for the authentication of the 'Nocciola Romana' hazelnut (Corylus
      avellana L. cvs Tonda Gentile Romana and Nocchione) as a Protected Designation of
      Origin (PDO) hazelnut from central Italy. Algorithms for the selection of the
      optimal pretreatments were tested in combination with the following discriminant
      routines: k-nearest neighbour, soft independent modelling of class analogy,
      partial least squares discriminant analysis and support vector machine
      discriminant analysis. RESULTS: The best results were obtained using a support
      vector machine discriminant analysis routine. Thus, classification performance
      rates with specificities, sensitivities and accuracies as high as 96.0%, 95.0%
      and 95.5%, respectively, were achieved. Various pretreatments, such as standard
      normal variate, mean centring and a Savitzky-Golay filter with seven smoothing
      points, were used. The optimal wavelengths for classification were mainly
      correlated with lipids, although some contribution from minor constituents, such
      as proteins and carbohydrates, was also observed. CONCLUSION: Near infrared
      spectroscopy could classify hazelnut according to the PDO 'Nocciola Romana'
      designation. Thus, the experimentation lays the foundations for a rapid, online,
      authentication system for hazelnut. However, model robustness should be improved
      taking into account agro-pedo-climatic growing conditions.

PMID- 25378146
TI  - Bioinspired self-assembly of tyrosinase-modified silicatein and fluorescent core
      shell silica spheres.
AB  - Inspired by the intermolecular cross-linking of mussel foot proteins and their
      adhesive properties, tyrosinase has been used to modify recombinant silicatein.
      DOPA/DOPAquinone-mediated cross-linking and interfacial interactions enhanced
      both self-assembly of silicatein building blocks and templating of core-shell
      silica spheres, resulting in fluorescent biomimetic silicatein-silica hybrid
      mesofibers. 

PMID- 25378148
TI  - Can object category-selectivity in the ventral visual pathway be explained by
      sensitivity to low-level image properties?

PMID- 25378147
TI  - Vitamin D and skin cancer.
AB  - Vitamin D signaling plays a key role in many important processes, including
      cellular proliferation, differentiation and apoptosis, immune regulation, hormone
      secretion and skeletal health. Furthermore, vitamin D production and
      supplementation have been shown to exert protective effects via an unknown
      signaling mechanism involving the vitamin D receptor (VDR) in several diseases
      and cancer types, including skin cancer. With over 3.5 million new diagnoses in 2
      million patients annually, skin cancer is the most common cancer type in the
      United States. While ultraviolet B (UVB) radiation is the main etiologic factor
      for nonmelanoma skin cancer (NMSC), UVB also induces cutaneous vitamin D
      production. This paradox has been the subject of contradictory findings in the
      literature in regards to amount of sun exposure necessary for appropriate vitamin
      D production, as well as any beneficial or detrimental effects of vitamin D
      supplementation for disease prevention. Further clinical and epidemiological
      studies are necessary to elucidate the role of vitamin D in skin carcinogenesis.

PMID- 25378149
TI  - Caspr and caspr2 are required for both radial and longitudinal organization of
      myelinated axons.
AB  - In myelinated peripheral axons, Kv1 potassium channels are clustered at the
      juxtaparanodal region and at an internodal line located along the mesaxon and
      below the Schmidt-Lanterman incisures. This polarized distribution is controlled
      by Schwann cells and requires specific cell adhesion molecules (CAMs). The
      accumulation of Kv1 channels at the juxtaparanodal region depends on the presence
      of Caspr2 at this site, as well as on the presence of Caspr at the adjacent
      paranodal junction. However, the localization of these channels along the
      mesaxonal internodal line still persists in the absence of each one of these
      CAMs. By generating mice lacking both Caspr and Caspr2 (caspr(-/-)/caspr2(-/-)),
      we now reveal compensatory functions of the two proteins in the organization of
      the axolemma. Although Kv1 channels are clustered along the inner mesaxon and in
      a circumferential ring below the incisures in the single mutants, in sciatic
      nerves of caspr(-/-)/caspr2(-/-) mice, these channels formed large aggregates
      that were dispersed along the axolemma, demonstrating that internodal
      localization of Kv1 channels requires either Caspr or Caspr2. Furthermore,
      deletion of both Caspr and Caspr2 also resulted in widening of the nodes of
      Ranvier, suggesting that Caspr2 (which is present at paranodes in the absence of
      Caspr) can partially compensate for the barrier function of Caspr at this site
      even without the formation of a distinct paranodal junction. Our results indicate
      that Caspr and Caspr2 are required for the organization of the axolemma both
      radially, manifested as the mesaxonal line, and longitudinally, demarcated by the
      nodal domains.

PMID- 25378150
TI  - Mirror neuron activation prior to action observation in a predictable context.
AB  - A fundamental capacity of social animals consists in the predictive
      representation of upcoming events in the outside world, such as the actions of
      others. Here, we tested the activity of ventral premotor area F5 mirror neurons
      (MNs) while monkeys observed an experimenter performing (Action condition) or
      withholding (Inaction condition) a grasping action, which could be predicted on
      the basis of previously presented auditory instructions. Many of the recorded MNs
      discharged only during action observation (Action MNs), but one-third also
      encoded the experimenter's withheld action (Inaction MNs). Interestingly, while
      most of Action MNs exhibited reactive discharge during action observation,
      becoming active after the go signal, the majority of Inaction MNs showed
      predictive discharge. MN population activity as a whole displayed an overall
      predictive activation pattern, becoming active, on average, 340 ms before the go
      signal. Furthermore, MNs became active earlier when the observed action was
      performed in the monkeys' extrapersonal rather than peripersonal space,
      suggesting that context-based neural prediction of others' actions plays
      different roles depending on the monkeys' ability to interact with the observed
      agent.

PMID- 25378151
TI  - The effects of incentive framing on performance decrements for large monetary
      outcomes: behavioral and neural mechanisms.
AB  - There is a nuanced interplay between the provision of monetary incentives and
      behavioral performance. Individuals' performance typically increases with
      increasing incentives only up to a point, after which larger incentives may
      result in decreases in performance, a phenomenon known as "choking." We
      investigated the influence of incentive framing on choking effects in humans: in
      one condition, participants performed a skilled motor task to obtain potential
      monetary gains; in another, participants performed the same task to avoid losing
      a monetary amount. In both the gain and loss frame, the degree of participants'
      behavioral loss aversion was correlated with their susceptibility to choking
      effects. However, the effects were markedly different in the gain and loss
      frames: individuals with higher loss aversion were susceptible to choking for
      large prospective gains and not susceptible to choking for large prospective
      losses, whereas individuals with low loss aversion choked for large prospective
      losses but not for large prospective gains. Activity in the ventral striatum was
      predictive of performance decrements in both the gain and loss frames. Moreover,
      a mediation analysis revealed that behavioral loss aversion hindered performance
      via the influence of ventral striatal activity on motor performance. Our findings
      indicate that the framing of an incentive has a profound effect on an
      individual's susceptibility to choking effects, which is contingent on their loss
      aversion. Furthermore, we demonstrate that the ventral striatum serves as an
      interface between incentive-driven motivation and instrumental action, regardless
      of whether incentives are framed in terms of potential losses or gains.

PMID- 25378152
TI  - Cerebellar-dependent expression of motor learning during eyeblink conditioning in
      head-fixed mice.
AB  - Eyeblink conditioning in restrained rabbits has served as an excellent model of
      cerebellar-dependent motor learning for many decades. In mice, the role of the
      cerebellum in eyeblink conditioning is less clear and remains controversial,
      partly because learning appears to engage fear-related circuits and lesions of
      the cerebellum do not abolish the learned behavior completely. Furthermore,
      experiments in mice are performed using freely moving systems, which lack the
      stability necessary for mapping out the essential neural circuitry with
      electrophysiological approaches. We have developed a novel apparatus for eyeblink
      conditioning in head-fixed mice. Here, we show that the performance of mice in
      our apparatus is excellent and that the learned behavior displays two hallmark
      features of cerebellar-dependent eyeblink conditioning in rabbits: (1) gradual
      acquisition; and (2) adaptive timing of conditioned movements. Furthermore, we
      use a combination of pharmacological inactivation, electrical stimulation, single
      unit recordings, and targeted microlesions to demonstrate that the learned
      behavior is completely dependent on the cerebellum and to pinpoint the exact
      location in the deep cerebellar nuclei that is necessary. Our results pave the
      way for using eyeblink conditioning in head-fixed mice as a platform for applying
      next-generation genetic tools to address molecular and circuit-level questions
      about cerebellar function in health and disease.

PMID- 25378153
TI  - Nucleotide bound to rab11a controls localization in rod cells but not interaction
      with rhodopsin.
AB  - Precise vectorial transport of rhodopsin is essential for rod photoreceptor
      health and function. Mutations that truncate or extend the C terminus of
      rhodopsin disrupt this transport, and lead to retinal degeneration and blindness
      in human patients and in mouse models. Here we show that such mutations disrupt
      the binding of rhodopsin to the small GTPase rab11a. The rhodopsin-rab11a
      interaction is a direct binding interaction that does not depend on the
      nucleotide binding state of rab11a. Expression of EGFP-rab11a fusion proteins in
      Xenopus laevis photoreceptors revealed that the nucleotide binding status of
      rab11a affects its subcellular localization, with GTP-locked mutants concentrated
      in the inner segment and GDP-locked mutants concentrated in the outer segment.
      shRNA-mediated knockdown of rab11a in rods led to shortened outer segments and
      retinal degeneration. Together, our results show the critical importance of
      direct rhodopsin-rab11a interactions for the formation and maintenance of
      vertebrate photoreceptors.

PMID- 25378154
TI  - A designated odor-language integration system in the human brain.
AB  - Odors are surprisingly difficult to name, but the mechanism underlying this
      phenomenon is poorly understood. In experiments using event-related potentials
      (ERPs) and functional magnetic resonance imaging (fMRI), we investigated the
      physiological basis of odor naming with a paradigm where olfactory and visual
      object cues were followed by target words that either matched or mismatched the
      cue. We hypothesized that word processing would not only be affected by its
      semantic congruency with the preceding cue, but would also depend on the cue
      modality (olfactory or visual). Performance was slower and less precise when
      linking a word to its corresponding odor than to its picture. The ERP index of
      semantic incongruity (N400), reflected in the comparison of nonmatching versus
      matching target words, was more constrained to posterior electrode sites and
      lasted longer on odor-cue (vs picture-cue) trials. In parallel, fMRI cross
      adaptation in the right orbitofrontal cortex (OFC) and the left anterior temporal
      lobe (ATL) was observed in response to words when preceded by matching olfactory
      cues, but not by matching visual cues. Time-series plots demonstrated increased
      fMRI activity in OFC and ATL at the onset of the odor cue itself, followed by
      response habituation after processing of a matching (vs nonmatching) target word,
      suggesting that predictive perceptual representations in these regions are
      already established before delivery and deliberation of the target word.
      Together, our findings underscore the modality-specific anatomy and physiology of
      object identification in the human brain.

PMID- 25378155
TI  - Impaired action potential initiation in GABAergic interneurons causes
      hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1
      mutation.
AB  - Mutations in SCN1A and other ion channel genes can cause different epileptic
      phenotypes, but the precise mechanisms underlying the development of
      hyperexcitable networks are largely unknown. Here, we present a multisystem
      analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which
      causes febrile seizures and epilepsy in humans. We found a ubiquitous
      hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without
      detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels
      in interneurons and persistent Na(+) currents were not significantly changed.
      Instead, the key mechanism of interneuron dysfunction was a deficit of action
      potential initiation at the axon initial segment that was identified by analyzing
      action potential firing. This deficit increased with the duration of firing
      periods, suggesting that increased slow inactivation, as recorded for recombinant
      mutated channels, could play an important role. The deficit in interneuron firing
      caused reduced action potential-driven inhibition of excitatory neurons as
      revealed by less frequent spontaneous but not miniature IPSCs. Multiple
      approaches indicated increased spontaneous thalamocortical and hippocampal
      network activity in mutant mice, as follows: (1) more synchronous and higher
      frequency firing was recorded in primary neuronal cultures plated on
      multielectrode arrays; (2) thalamocortical slices examined by field potential
      recordings revealed spontaneous activities and pathological high-frequency
      oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed
      increased spontaneous neuronal activity. Thus, an interneuron-specific
      generalized defect in action potential initiation causes multisystem
      disinhibition and network hyperexcitability, which can well explain the
      occurrence of seizures in the studied mouse model and in patients carrying this
      mutation.

PMID- 25378156
TI  - Prolonged deficits in parvalbumin neuron stimulation-evoked network activity
      despite recovery of dendritic structure and excitability in the somatosensory
      cortex following global ischemia in mice.
AB  - Relatively few studies have examined plasticity of inhibitory neuronal networks
      following stroke in vivo, primarily due to the inability to selectively monitor
      inhibition. We assessed the structure of parvalbumin (PV) interneurons during a 5
      min period of global ischemia and reperfusion in mice, which mimicked cerebral
      ischemia during cardiac arrest or forms of transient ischemic attack. The
      dendritic structure of PV-neurons in cortical superficial layers was rapidly
      swollen and beaded during global ischemia, but recovered within 5-10 min
      following reperfusion. Using optogenetics and a multichannel optrode, we
      investigated the function of PV-neurons in mouse forelimb somatosensory cortex.
      We demonstrated pharmacologically that PV-channelrhodopsin-2 (ChR2) stimulation
      evoked activation in layer IV/V, which resulted in rapid current sinks mediated
      by photocurrent and action potentials (a measure of PV-neuron excitability),
      which was then followed by current sources mediated by network GABAergic synaptic
      activity. During ischemic depolarization, the PV-ChR2-evoked current sinks
      (excitability) were suppressed, but recovered rapidly following reperfusion
      concurrent with repolarization of the DC-EEG. In contrast, the current sources
      reflecting GABAergic synaptic network activity recovered slowly and incompletely,
      and was coincident with the partial recovery of the forepaw stimulation-evoked
      current sinks in layer IV/V 30 min post reperfusion. Our in vivo data suggest
      that the excitability of PV inhibitory neurons was suppressed during global
      ischemia and rapidly recovered during reperfusion. In contrast, PV-ChR2
      stimulation-evoked GABAergic synaptic network activity exhibited a prolonged
      suppression even ~1 h after reperfusion, which could contribute to the
      dysfunction of sensation and cognition following transient global ischemia.

PMID- 25378157
TI  - Episodic memory encoding interferes with reward learning and decreases striatal
      prediction errors.
AB  - Learning is essential for adaptive decision making. The striatum and its
      dopaminergic inputs are known to support incremental reward-based learning, while
      the hippocampus is known to support encoding of single events (episodic memory).
      Although traditionally studied separately, in even simple experiences, these two
      types of learning are likely to co-occur and may interact. Here we sought to
      understand the nature of this interaction by examining how incremental reward
      learning is related to concurrent episodic memory encoding. During the
      experiment, human participants made choices between two options (colored
      squares), each associated with a drifting probability of reward, with the goal of
      earning as much money as possible. Incidental, trial-unique object pictures,
      unrelated to the choice, were overlaid on each option. The next day, participants
      were given a surprise memory test for these pictures. We found that better
      episodic memory was related to a decreased influence of recent reward experience
      on choice, both within and across participants. fMRI analyses further revealed
      that during learning the canonical striatal reward prediction error signal was
      significantly weaker when episodic memory was stronger. This decrease in reward
      prediction error signals in the striatum was associated with enhanced functional
      connectivity between the hippocampus and striatum at the time of choice. Our
      results suggest a mechanism by which memory encoding may compete for striatal
      processing and provide insight into how interactions between different forms of
      learning guide reward-based decision making.

PMID- 25378158
TI  - Constrained by our connections: white matter's key role in interindividual
      variability in visual working memory capacity.
AB  - Visual working memory (VWM) plays an essential role in many perceptual and higher
      order cognitive processes. Despite its reliance on a broad network of brain
      regions, VWM has a capacity limited to a few objects. This capacity varies
      substantially across individuals and relates closely to measures of overall
      cognitive function (Luck and Vogel, 2013). The mechanisms underlying these
      properties are not completely understood, although the amplitude of neural signal
      oscillations (Vogel and Machizawa, 2004) and brain activation in specific
      cortical regions (Todd and Marois, 2004) have been implicated. Variability in VWM
      performance may also reflect variability in white matter structural properties.
      However, data based primarily on diffusion tensor imaging approaches remain
      inconclusive. Here, we investigate the relationship between white matter and VWM
      capacity in human subjects using an advanced diffusion imaging technique,
      diffusion kurtosis imaging. Diffusion kurtosis imaging provides several novel
      quantitative white mater metrics, among them the axonal water fraction (f(axon)),
      an index of axonal density and caliber. Our results show that 59% of individual
      variability in VWM capacity may be explained by variations in f(axon) within a
      widely distributed network of white matter tracts. Increased f(axon) associates
      with increased VWM capacity. An additional 12% in VWM capacity variance may be
      explained by diffusion properties of the extra-axonal space. These data
      demonstrate, for the first time, the key role of white matter in limiting VWM
      capacity in the healthy adult brain and suggest that white matter may represent
      an important therapeutic target in disorders of impaired VWM and cognition.

PMID- 25378160
TI  - Effects of luminance contrast on the color selectivity of neurons in the macaque
      area v4 and inferior temporal cortex.
AB  - Appearance of a color stimulus is significantly affected by the contrast between
      its luminance and the luminance of the background. In the present study, we used
      stimuli evenly distributed on the CIE-xy chromaticity diagram to examine how
      luminance contrast affects neural representation of color in V4 and the anterior
      inferior temporal (AITC) and posterior inferior temporal (PITC) color areas
      (Banno et al., 2011). The activities of single neurons were recorded from monkeys
      performing a visual fixation task, and the effects of luminance contrast on the
      color selectivity of individual neurons and their population responses were
      systematically examined by comparing responses to color stimuli that were
      brighter or darker than the background. We found that the effects of luminance
      contrast differed considerably across V4 and the PITC and AITC. In both V4 and
      the PITC, the effects of luminance contrast on the population responses of color
      selective neurons depended on color. In V4, the size of the effect was largest
      for blue and cyan, whereas in the PITC, the effect gradually increased as the
      saturation of the color stimulus was reduced, and was especially large with
      neutral colors (white, gray, black). The pattern observed in the PITC resembles
      the effect of luminance contrast on color appearance, suggesting PITC neurons are
      closely involved in the formation of the perceived appearance of color. By
      contrast, the color selectivities of AITC neurons were little affected by
      luminance contrast, indicating that hue and saturation of color stimuli are
      represented independently of luminance contrast in the AITC. 

PMID- 25378159
TI  - Synaptic and cognitive improvements by inhibition of 2-AG metabolism are through
      upregulation of microRNA-188-3p in a mouse model of Alzheimer's disease.
AB  - Abnormal accumulation of beta-amyloid (Abeta) is the major neuropathological
      hallmark of Alzheimer's disease (AD). However, the mechanisms underlying aberrant
      Abeta formation in AD remain unclear. We showed previously that inhibition of
      monoacylglycerol lipase (MAGL), the primary enzyme that metabolizes the
      endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain, robustly reduces
      Abeta by inhibiting beta-site amyloid precursor protein cleaving enzyme 1
      (BACE1), a key enzyme responsible for Abeta formation. However, the molecular
      mechanisms responsible for suppression of BACE1 by inhibition of 2-AG metabolism
      are largely unknown. We demonstrate here that expression of the noncoding small
      RNA miR-188-3p that targets BACE1 was significantly downregulated both in the
      brains of AD humans and APP transgenic (TG) mice, a mouse model of AD. The
      downregulated miR-188-3p expression was restored by MAGL inhibition.
      Overexpression of miR-188-3p in the hippocampus reduced BACE1, Abeta, and
      neuroinflammation and prevented deteriorations in hippocampal basal synaptic
      transmission, long-term potentiation, spatial learning, and memory in TG mice. 2
      AG-induced suppression of BACE1 was prevented by miR-188-3p loss of function.
      Moreover, miR-188-3p expression was upregulated by 2-AG or peroxisome
      proliferator-activated receptor-gamma (PPARgamma) agonists and suppressed by
      PPARgamma antagonism or NF-kappaB activation. Reducing Abeta and
      neuroinflammation by MAGL inhibition was occluded by PPARgamma antagonism. In
      addition, BACE1 suppression by 2-AG and PPARgamma activation was eliminated by
      knockdown of NF-kappaB. Our study provides a novel molecular mechanism underlying
      improved synaptic and cognitive function in TG mice by 2-AG signaling, which
      upregulates miR-188-3p expression through PPARgamma and NF-kappaB signaling
      pathway, resulting in suppressions of BACE1 expression and Abeta formation.

PMID- 25378161
TI  - Parvalbumin and GAD65 interneuron inhibition in the ventral hippocampus induces
      distinct behavioral deficits relevant to schizophrenia.
AB  - Hyperactivity within the ventral hippocampus (vHPC) has been linked to both
      psychosis in humans and behavioral deficits in animal models of schizophrenia. A
      local decrease in GABA-mediated inhibition, particularly involving parvalbumin
      (PV)-expressing GABA neurons, has been proposed as a key mechanism underlying
      this hyperactive state. However, direct evidence is lacking for a causal role of
      vHPC GABA neurons in behaviors associated with schizophrenia. Here, we probed the
      behavioral function of two different but overlapping populations of vHPC GABA
      neurons that express either PV or GAD65 by selectively inhibiting these neurons
      with the pharmacogenetic neuromodulator hM4D. We show that acute inhibition of
      vHPC GABA neurons in adult mice results in behavioral changes relevant to
      schizophrenia. Inhibiting either PV or GAD65 neurons produced distinct behavioral
      deficits. Inhibition of PV neurons, affecting ~80% of the PV neuron population,
      robustly impaired prepulse inhibition of the acoustic startle reflex (PPI),
      startle reactivity, and spontaneous alternation, but did not affect locomotor
      activity. In contrast, inhibiting a heterogeneous population of GAD65 neurons,
      affecting ~40% of PV neurons and 65% of cholecystokinin neurons, increased
      spontaneous and amphetamine-induced locomotor activity and reduced spontaneous
      alternation, but did not alter PPI. Inhibition of PV or GAD65 neurons also
      produced distinct changes in network oscillatory activity in the vHPC in vivo.
      Together, these findings establish a causal role for vHPC GABA neurons in
      controlling behaviors relevant to schizophrenia and suggest a functional
      dissociation between the GABAergic mechanisms involved in hippocampal modulation
      of sensorimotor processes.

PMID- 25378162
TI  - Wnt5 and drl/ryk gradients pattern the Drosophila olfactory dendritic map.
AB  - During development, dendrites migrate to their correct locations in response to
      environmental cues. The mechanisms of dendritic guidance are poorly understood.
      Recent work has shown that the Drosophila olfactory map is initially formed by
      the spatial segregation of the projection neuron (PN) dendrites in the developing
      antennal lobe (AL). We report here that between 16 and 30 h after puparium
      formation, the PN dendrites undergo dramatic rotational reordering to achieve
      their final glomerular positions. During this period, a novel set of AL-extrinsic
      neurons express high levels of the Wnt5 protein and are tightly associated with
      the dorsolateral edge of the AL. Wnt5 forms a dorsolateral-high to ventromedial
      low pattern in the antennal lobe neuropil. Loss of Wnt5 prevents the ventral
      targeting of the dendrites, whereas Wnt5 overexpression disrupts dendritic
      patterning. We find that Drl/Ryk, a known Wnt5 receptor, is expressed in a
      dorsolateral-to-ventromedial (DL > VM) gradient by the PN dendrites. Loss of Drl
      in the PNs results in the aberrant ventromedial targeting of the dendrites, a
      defect that is suppressed by reduction in Wnt5 gene dosage. Conversely,
      overexpression of Drl in the PNs results in the dorsolateral targeting of their
      dendrites, an effect that requires Drl's cytoplasmic domain. We propose that Wnt5
      acts as a repulsive guidance cue for the PN dendrites, whereas Drl signaling in
      the dendrites inhibits Wnt5 signaling. In this way, the precise expression
      patterns of Wnt5 and Drl orient the PN dendrites allowing them to target their
      final glomerular positions.

PMID- 25378163
TI  - Migration of oligodendrocyte progenitor cells is controlled by transforming
      growth factor beta family proteins during corticogenesis.
AB  - During embryonic development oligodendrocyte precursor cells (OPCs) are generated
      first in the ventral forebrain and migrate dorsally to occupy the cortex. The
      molecular cues that guide this migratory route are currently completely unknown.
      Here, we show that bone morphogenetic protein-4 (Bmp4), Bmp7, and Tgfbeta1
      produced by the meninges and pericytes repelled ventral OPCs into the cortex at
      mouse embryonic stages. Ectopic activation of Bmp or Tgfbeta1 signaling before
      the entrance of OPCs into the cortex hindered OPC migration into the cortical
      areas. OPCs without Smad4 signaling molecules also failed to migrate into the
      cortex efficiently and formed heterotopia in ventral areas. OPC migration into
      the cortex was also dramatically reduced by conditional inhibition of Tgfbeta1 or
      Bmp expression from mesenchymal cells. The data suggest that mesenchymal Tgfbeta
      family proteins promote migration of ventral OPCs into the cortex during
      corticogenesis.

PMID- 25378164
TI  - Millisecond timescale synchrony among hippocampal neurons.
AB  - Inhibitory neurons in cortical circuits play critical roles in composing spike
      timing and oscillatory patterns in neuronal activity. These roles in turn require
      coherent activation of interneurons at different timescales. To investigate how
      the local circuitry provides for these activities, we applied resampled cross
      correlation analyses to large-scale recordings of neuronal populations in the
      cornu ammonis 1 (CA1) and CA3 regions of the hippocampus of freely moving rats.
      Significant counts in the cross-correlation of cell pairs, relative to jittered
      surrogate spike-trains, allowed us to identify the effective couplings between
      neurons in CA1 and CA3 hippocampal regions on the timescale of milliseconds. In
      addition to putative excitatory and inhibitory monosynaptic connections, we
      uncovered prominent millisecond timescale synchrony between cell pairs, observed
      as peaks in the central 0 ms bin of cross-correlograms. This millisecond
      timescale synchrony appeared to be independent of network state, excitatory
      input, and gamma oscillations. Moreover, it was frequently observed between cells
      of differing putative interneuronal type, arguing against gap junctions as the
      sole underlying source. Our observations corroborate recent in vitro findings
      suggesting that inhibition alone is sufficient to synchronize interneurons at
      such fast timescales. Moreover, we show that this synchronous spiking may cause
      stronger inhibition and rebound spiking in target neurons, pointing toward a
      potential function for millisecond synchrony of interneurons in shaping and
      affecting timing in pyramidal populations within and downstream from the circuit.

PMID- 25378165
TI  - Girdin phosphorylation is crucial for synaptic plasticity and memory: a potential
      role in the interaction of BDNF/TrkB/Akt signaling with NMDA receptor.
AB  - Synaptic plasticity in hippocampal neurons has been thought to represent a
      variety of memories. Although accumulating evidence indicates a crucial role of
      BDNF/TrkB/Akt signaling in the synaptic plasticity of the hippocampus, the
      mechanism by which Akt, a serine/threonine kinase, controls activity-dependent
      neuronal plasticity remains unclear. Girdin (also known as APE, GIV, and HkRP1),
      an actin-binding protein involved both in the remodeling of the actin
      cytoskeleton and in cell migration, has been identified as a substrate of Akt.
      Previous studies have demonstrated that deficit of neuronal migration in the
      hippocampus of Girdin-deficient (Girdin(-/-)) mice is independent on serine
      phosphorylation of Girdin at S1416 (Girdin S1416) by Akt. In the present study,
      we focused on the role of Girdin S1416 phosphorylation in BDNF/TrkB/Akt signaling
      associated with synaptic plasticity. We found that Girdin in the hippocampus was
      phosphorylated at S1416 in an activity-dependent manner. Phosphorylation
      deficient knock-in mice (Girdin(SA/SA) mice), in which S1416 is replaced with
      alanine, exhibited shrinkage of spines, deficit of hippocampal long-term
      potentiation, and memory impairment. These phenotypes of Girdin(SA/SA) mice
      resembled those of Girdin(+/-) mice, which have 50% loss of Girdin expression.
      Furthermore, Girdin interacted with Src kinase and NR2B subunit of NMDA receptor,
      leading to phosphorylation of the NR2B subunit and NMDA receptor activation. Our
      findings suggest that Girdin has two different functions in the hippocampus: Akt
      independent neuronal migration and Akt-dependent NR2B phosphorylation through the
      interaction with Src, which is associated with synaptic plasticity in the
      hippocampus underlying memory formation.

PMID- 25378166
TI  - Permittivity coupling across brain regions determines seizure recruitment in
      partial epilepsy.
AB  - Brain regions generating seizures in patients with refractory partial epilepsy
      are referred to as the epileptogenic zone (EZ). During a seizure, paroxysmal
      activity is not restricted to the EZ, but may recruit other brain regions and
      propagate activity through large brain networks, which comprise brain regions
      that are not necessarily epileptogenic. The identification of the EZ is crucial
      for candidates for neurosurgery and requires unambiguous criteria that evaluate
      the degree of epileptogenicity of brain regions. To obtain such criteria and
      investigate the mechanisms of seizure recruitment and propagation, we develop a
      mathematical framework of coupled neural populations, which can interact via
      signaling through a slow permittivity variable. The permittivity variable
      captures effects evolving on slow timescales, including extracellular ionic
      concentrations and energy metabolism, with time delays of up to seconds as
      observed clinically. Our analyses provide a set of indices quantifying the degree
      of epileptogenicity and predict conditions, under which seizures propagate to
      nonepileptogenic brain regions, explaining the responses to intracerebral
      electric stimulation in epileptogenic and nonepileptogenic areas. In conjunction,
      our results provide guidance in the presurgical evaluation of epileptogenicity
      based on electrographic signatures in intracerebral electroencephalograms.

PMID- 25378167
TI  - Back to the future: preserved hippocampal network activity during reverse
      ambulation.
AB  - During movement, there is a transition of activity across the population, such
      that place-field centers ahead of the rat are sequentially activated in the order
      that they will be encountered. Although the mechanisms responsible for this
      sequence updating are unknown, two classes of models can be considered. The first
      class involves head-direction information for activating neurons in the order
      that their place fields will be traversed. An alternative model contends that
      motion and turn-related information from the posterior parietal cortex shift the
      subset of active hippocampal cells across the population. To explicitly test
      these two models, rodents were trained to run backward on a linear track, placing
      movement in opposition with head orientation. Although head-direction did not
      change between running conditions, place-field activity remapped and there was an
      increase in place-field size during backward running compared with forward. The
      population activity, however, could still be used to reconstruct the location of
      the rat accurately. Moreover, theta phase precession was maintained in both
      running conditions, indicating preservation of place-field sequences on short
      time scales. The observation that sequence encoding persists even when the animal
      is orientated away from the direction of movement favors the concept that
      posterior parietal cortical mechanisms may be partially responsible for updating
      hippocampal activity patterns. 

PMID- 25378168
TI  - Development of intrinsic connectivity in the central nucleus of the mouse
      inferior colliculus.
AB  - The inferior colliculus (IC) in the mammalian midbrain is the major subcortical
      auditory integration center receiving ascending inputs from almost all auditory
      brainstem nuclei as well as descending inputs from the thalamus and cortex. In
      addition to these extrinsic inputs, the IC also contains a dense network of
      local, intracollicular connections, which are thought to provide gain control and
      contribute to the selectivity for complex acoustic features. However, in contrast
      to the organization of extrinsic IC afferents, the development and functional
      organization of intrinsic connections in the IC has remained poorly understood.
      Here we used laser-scanning photostimulation with caged glutamate to characterize
      the spatial distribution and strength of local synaptic connections in the
      central nucleus of the inferior colliculus of newborn mice until after hearing
      onset (P2-P22). We demonstrate the presence of an extensive excitatory and
      inhibitory intracollicular network already at P2. Excitatory and inhibitory
      synaptic maps to individual IC neurons formed continuous maps that largely
      overlapped with each other and that were aligned with the presumed isofrequency
      axis of the central nucleus of the IC. Although this characteristic organization
      was present throughout the first three postnatal weeks, the size of input maps
      was developmentally regulated as input maps underwent an expansion during the
      first week that was followed by a dramatic refinement after hearing onset. These
      changes occurred in parallel for excitatory and inhibitory input maps. However,
      the functional elimination of intrinsic connections was greater for excitatory
      than for inhibitory connections, resulting in a predominance of intrinsic
      inhibition after hearing onset.

PMID- 25378169
TI  - Neural substrates of view-invariant object recognition developed without
      experiencing rotations of the objects.
AB  - One fails to recognize an unfamiliar object across changes in viewing angle when
      it must be discriminated from similar distractor objects. View-invariant
      recognition gradually develops as the viewer repeatedly sees the objects in
      rotation. It is assumed that different views of each object are associated with
      one another while their successive appearance is experienced in rotation.
      However, natural experience of objects also contains ample opportunities to
      discriminate among objects at each of the multiple viewing angles. Our previous
      behavioral experiments showed that after experiencing a new set of object stimuli
      during a task that required only discrimination at each of four viewing angles at
      30 degrees  intervals, monkeys could recognize the objects across changes in
      viewing angle up to 60 degrees . By recording activities of neurons from the
      inferotemporal cortex after various types of preparatory experience, we here
      found a possible neural substrate for the monkeys' performance. For object sets
      that the monkeys had experienced during the task that required only
      discrimination at each of four viewing angles, many inferotemporal neurons showed
      object selectivity covering multiple views. The degree of view generalization
      found for these object sets was similar to that found for stimulus sets with
      which the monkeys had been trained to conduct view-invariant recognition. These
      results suggest that the experience of discriminating new objects in each of
      several viewing angles develops the partially view-generalized object selectivity
      distributed over many neurons in the inferotemporal cortex, which in turn bases
      the monkeys' emergent capability to discriminate the objects across changes in
      viewing angle.

PMID- 25378171
TI  - MicroRNA-19b associates with Ago2 in the amygdala following chronic stress and
      regulates the adrenergic receptor beta 1.
AB  - Activation of the stress response in the presence of diverse challenges requires
      numerous adaptive molecular and cellular changes. To identify specific microRNA
      molecules that are altered following chronic stress, mice were subjected to the
      chronic social defeat procedure. The amygdala from these mice was collected and a
      screen for microRNAs that were recruited to the RNA-induced silencing complex and
      differentially expressed between the stressed and unstressed mice was conducted.
      One of the microRNAs that were significantly altered was microRNA-19b (miR-19b).
      Bioinformatics analysis revealed the adrenergic receptor beta-1 (Adrb1) as a
      potential target for this microRNA with multiple conserved seed sites. Consistent
      with its putative regulation by miR-19b, Adrb1 levels were reduced in the
      basolateral amygdala (BLA) following chronic stress. In vitro studies using
      luciferase assays showed a direct effect of miR-19b on Adrb1 levels, which were
      not evident when miR-19b seed sequences at the Adrb1 transcript were mutated. To
      assess the role of miR-19b in memory stabilization, previously attributed to BLA
      Adrb1, we constructed lentiviruses designed to overexpress or knockdown miR-19b.
      Interestingly, adult mice injected bilaterally with miR-19b into the BLA showed
      lower freezing time relative to control in the cue fear conditioning test, and
      deregulation of noradrenergic circuits, consistent with downregulation of Adrb1
      levels. Knockdown of endogenous BLA-miR-19b levels resulted in opposite
      behavioral and noradrenergic profile with higher freezing time and increase 3
      methoxy-4-hydroxyphenylglycol/noradrenaline ratio. These findings suggest a key
      role for miR-19b in modulating behavioral responses to chronic stress and Adrb1
      as an important target of miR-19b in stress-linked brain regions. 

PMID- 25378170
TI  - Development of gonadotropin-releasing hormone secretion and pituitary response.
AB  - Acquisition of a mature pattern of gonadotropin-releasing hormone (GnRH)
      secretion from the CNS is a hallmark of the pubertal process. Little is known
      about GnRH release during sexual maturation, but it is assumed to be minimal
      before later stages of puberty. We studied spontaneous GnRH secretion in brain
      slices from male mice during perinatal and postnatal development using fast-scan
      cyclic voltammetry (FSCV) to detect directly the oxidation of secreted GnRH.
      There was good correspondence between the frequency of GnRH release detected by
      FSCV in the median eminence of slices from adults with previous reports of in
      vivo luteinizing hormone (LH) pulse frequency. The frequency of GnRH release in
      the late embryonic stage was surprisingly high, reaching a maximum in newborns
      and remaining elevated in 1-week-old animals despite low LH levels. Early high
      frequency GnRH release was similar in wild-type and kisspeptin knock-out mice
      indicating that this release is independent of kisspeptin-mediated excitation. In
      vivo treatment with testosterone or in vitro treatment with gonadotropin
      inhibitory hormone (GnIH) reduced GnRH release frequency in slices from 1-week
      old mice. RF9, a putative GnIH antagonist, restored GnRH release in slices from
      testosterone-treated mice, suggesting that testosterone inhibition may be GnIH
      dependent. At 2-3 weeks, GnRH release is suppressed before attaining adult
      patterns. Reduction in early life spontaneous GnRH release frequency coincides
      with the onset of the ability of exogenous GnRH to induce pituitary LH secretion.
      These findings suggest that lack of pituitary secretory response, not lack of
      GnRH release, initially blocks downstream activation of the reproductive system.

PMID- 25378173
TI  - A model of synaptic vesicle-pool depletion and replenishment can account for the
      interspike interval distributions and nonrenewal properties of spontaneous spike
      trains of auditory-nerve fibers.
AB  - In mammalian auditory systems, the spiking characteristics of each primary
      afferent (type I auditory-nerve fiber; ANF) are mainly determined by a single
      ribbon synapse in a single receptor cell (inner hair cell; IHC). ANF spike trains
      therefore provide a window into the operation of these synapses and cells. It was
      demonstrated previously (Heil et al., 2007) that the distribution of interspike
      intervals (ISIs) of cat ANFs during spontaneous activity can be modeled as
      resulting from refractoriness operating on a non-Poisson stochastic point process
      of excitation (transmitter release events from the IHC). Here, we investigate
      nonrenewal properties of these cat-ANF spontaneous spike trains, manifest as
      negative serial ISI correlations and reduced spike-count variability over short
      timescales. A previously discussed excitatory process, the constrained failure of
      events from a homogeneous Poisson point process, can account for these
      properties, but does not offer a parsimonious explanation for certain trends in
      the data. We then investigate a three-parameter model of vesicle-pool depletion
      and replenishment and find that it accounts for all experimental observations,
      including the ISI distributions, with only the release probability varying
      between spike trains. The maximum number of units (single vesicles or groups of
      simultaneously released vesicles) in the readily releasable pool and their
      replenishment time constant can be assumed to be constant (~4 and 13.5 ms,
      respectively). We suggest that the organization of the IHC ribbon synapses not
      only enables sustained release of neurotransmitter but also imposes temporal
      regularity on the release process, particularly when operating at high rates.

PMID- 25378172
TI  - Direct visualization of trans-synaptic neurexin-neuroligin interactions during
      synapse formation.
AB  - Neurexins and neuroligins are synaptic cell-adhesion molecules that are essential
      for normal synapse specification and function and are thought to bind to each
      other trans-synaptically, but such interactions have not been demonstrated
      directly. Here, we generated neurexin-1beta and neuroligin-1 and neuroligin-2
      fusion proteins containing complementary "split" GFP fragments positioned such
      that binding of neurexin-1beta to neuroligin-1 or neuroligin-2 allowed GFP
      reconstitution without dramatically changing their binding affinities. GFP
      fluorescence was only reconstituted from split-GFP-modified neurexin-1beta and
      neuroligin-1 if and after neurexin-1beta bound to its neuroligin partner;
      reassociation of the split-GFP components with each other did not mediate
      binding. Using trans-cellular reconstitution of GFP fluorescence from split-GFP
      modified neurexin-1beta and neuroligins as an assay, we demonstrate that trans
      synaptic neurexin/neuroligin binding indeed occurred when mouse hippocampal
      neurons formed synapses onto non-neuronal COS-7 cells expressing neuroligins or
      when mouse hippocampal neurons formed synapses with each other. This
      visualization of synapses by neurexin/neuroligin binding prompted us to refer to
      this approach as "SynView." Our data demonstrate that neurexin-1beta forms a
      trans-synaptic complex with neuroligin-1 and neuroligin-2 and that this
      interaction can be used to label synapses in a specific fashion in vivo.

PMID- 25378174
TI  - Catecholaminergic C3 neurons are sympathoexcitatory and involved in glucose
      homeostasis.
AB  - Brainstem catecholaminergic neurons play key roles in the autonomic,
      neuroendocrine, and behavioral responses to glucoprivation, yet the functions of
      the individual groups are not fully understood. Adrenergic C3 neurons project
      widely throughout the brain, including densely to sympathetic preganglionic
      neurons in the spinal cord, yet their function is completely unknown. Here we
      demonstrate in rats that optogenetic stimulation of C3 neurons induces
      sympathoexcitatory, cardiovasomotor functions. These neurons are activated by
      glucoprivation, but unlike the C1 cell group, not by hypotension. The
      cardiovascular activation induced by C3 neurons is less than that induced by
      optogenetic stimulation of C1 neurons; however, combined stimulation produces
      additive sympathoexcitatory and cardiovascular effects. The varicose axons of C3
      neurons largely overlap with those of C1 neurons in the region of sympathetic
      preganglionic neurons in the spinal cord; however, regional differences point to
      effects on different sympathetic outflows. These studies definitively demonstrate
      the first known function of C3 neurons as unique cardiovasomotor stimulatory
      cells, embedded in the brainstem networks regulating cardiorespiratory activity
      and the response to glucoprivation.

PMID- 25378175
TI  - Transnitrosylation from DJ-1 to PTEN attenuates neuronal cell death in
      parkinson's disease models.
AB  - Emerging evidence suggests that oxidative/nitrosative stress, as occurs during
      aging, contributes to the pathogenesis of Parkinson's disease (PD). In contrast,
      detoxification of reactive oxygen species and reactive nitrogen species can
      protect neurons. DJ-1 has been identified as one of several recessively inherited
      genes whose mutation can cause familial PD, and inactivation of DJ-1 renders
      neurons more susceptible to oxidative stress and cell death. DJ-1 is also known
      to regulate the activity of the phosphatase and tensin homolog (PTEN), which
      plays a critical role in neuronal cell death in response to various insults.
      However, mechanistic details delineating how DJ-1 regulates PTEN activity remain
      unknown. Here, we report that PTEN phosphatase activity is inhibited via a
      transnitrosylation reaction [i.e., transfer of a nitric oxide (NO) group from the
      cysteine residue of one protein to another]. Specifically, we show that DJ-1 is S
      nitrosylated (forming SNO-DJ-1); subsequently, the NO group is transferred from
      DJ-1 to PTEN by transnitrosylation. Moreover, we detect SNO-PTEN in human brains
      with sporadic PD. Using x-ray crystallography and site-directed mutagenesis, we
      find that Cys106 is the site of S-nitrosylation on DJ-1 and that mutation of this
      site inhibits transnitrosylation to PTEN. Importantly, S-nitrosylation of PTEN
      decreases its phosphatase activity, thus promoting cell survival. These findings
      provide mechanistic insight into the neuroprotective role of SNO-DJ-1 by
      elucidating how DJ-1 detoxifies NO via transnitrosylation to PTEN. Dysfunctional
      DJ-1, which lacks this transnitrosylation activity due to mutation or prior
      oxidation (e.g., sulfonation) of the critical cysteine thiol, could thus
      contribute to neurodegenerative disorders like PD.

PMID- 25378176
TI  - Hydrogel design of experiments methodology to optimize hydrogel for iPSC-NPC
      culture.
AB  - Bioactive signals can be incorporated in hydrogels to direct encapsulated cell
      behavior. Design of experiments methodology methodically varies the signals
      systematically to determine the individual and combinatorial effects of each
      factor on cell activity. Using this approach enables the optimization of three
      ligands concentrations (RGD, YIGSR, IKVAV) for the survival and differentiation
      of neural progenitor cells. 

PMID- 25378177
TI  - Regulatory T cells in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE), an autoimmune disease, develops when
      immunologic self-tolerance fails. Treg cells are a subset of CD4(+) T cells that
      maintain self-tolerance by suppressing autoreactive lymphocytes. Defects in Treg
      cells are therefore considered to be an aspect of SLE pathogenesis. Nevertheless,
      reports on the numbers and function of Treg cells in SLE are contradictory and
      the definitive role of Treg cells in SLE remains unclear. In this review, we
      summarize findings from murine models and ex vivo experiments, which provide
      insights into the mechanisms that result in the breakdown of tolerance. We also
      include recent findings about Treg-cell subsets and their markers in human SLE.
      The identification of unique markers to identify bona fide Treg cells, as well as
      therapies to reconstitute the balance between Treg cells and autoreactive T cells
      in SLE, are the future challenges for SLE research. 

PMID- 25378178
TI  - BMI better explains hypertension in Chinese senior adults and the relationship
      declines with age.
AB  - BACKGROUND: Researchers have been examining the relationship between obesity and
      hypertension. However, whether overall or abdominal obesity better explains
      senior adults' hypertension has not been studied. OBJECTIVES: The purpose of the
      study was to examine whether body mass index or waist circumference better
      predicts hypertension in Chinese senior adults and how the magnitude of the
      relationship is attenuated as they continue to age. METHODS: The study was based
      on the 2010 National Physique Monitoring data. There were 7,542 senior adults
      aged 60-69 years living in urban, suburban, and rural areas of Shanghai City. The
      participants were categorized into five age groups: 60-61, 62-63, 64-65, 66-67,
      and 68-69 years. RESULTS: The percentage of participants who had hypertension
      increased as people aged, which was mainly caused by the increase of systolic
      blood pressure. Logistic regression analysis showed that when body mass index or
      waist circumference was entered into the model, both were significant predictors
      for hypertension (p < 0.05). However, when body mass index and waist
      circumference were mutually entered into the model, body mass index was the only
      important predictor (p < 0.05). The values of odds ratios were found to decrease
      from the 60-61 to 68-69 years age groups. More senior adults have hypertension as
      they age. CONCLUSION: Body mass index, and not waist circumference, better
      predicts Chinese senior adults' hypertension. However, age attenuates the effects
      of obesity on hypertension as the senior adults continue to age.

PMID- 25378180
TI  - Crystal structure of a bacterial homologue of SWEET transporters.

PMID- 25378179
TI  - The molecular mechanism of sporocyteless/nozzle in controlling Arabidopsis ovule
      development.
AB  - Ovules are essential for plant reproduction and develop into seeds after
      fertilization. Sporocyteless/nozzle (SPL/NZZ) has been known for more than 15
      years as an essential factor for ovule development in Arabidopsis, but the
      biochemical nature of SPL function has remained unsolved. Here, we demonstrate
      that SPL functions as an adaptor-like transcriptional repressor. We show that SPL
      recruits topless/topless-related (TPL/TPR) co-repressors to inhibit the
      Cincinnata (CIN)-like Teosinte branched1/cycloidea/PCF (TCP) transcription
      factors. We reveal that SPL uses its EAR motif at the C-terminal end to recruit
      TPL/TPRs and its N-terminal part to bind and inhibit the TCPs. We demonstrate
      that either disruption of TPL/TPRs or overexpression of TCPs partially
      phenocopies the defects of megasporogenesis in spl. Moreover, disruption of TCPs
      causes phenotypes that resemble spl-D gain-of-function mutants. These results
      define the action mechanism for SPL, which along with TPL/TPRs controls ovule
      development by repressing the activities of key transcription factors. Our
      findings suggest that a similar gene repression strategy is employed by both
      plants and fungi to control sporogenesis.

PMID- 25378181
TI  - Migrasomes: a new organelle of migrating cells.
AB  - Cell migration is a multi-step process that involves the coordinated action of
      signaling networks, cytoskeletal dynamics and vesicular trafficking, leading to
      protrusion and adhesion at the leading edge of cells and contraction and
      detachment at their rear. In a recent paper in Cell Research, Ma et al. describe
      the biogenesis of a new exosome-like organelle--named migrasomes--that derive
      from retraction fibers at the rear of migrating cells and their potential roles
      in inter-cellular signaling.

PMID- 25378182
TI  - Information causality in the quantum and post-quantum regime.
AB  - Quantum correlations can be stronger than anything achieved by classical systems,
      yet they are not reaching the limit imposed by relativity. The principle of
      information causality offers a possible explanation for why the world is quantum
      and why there appear to be no even stronger correlations. Generalizing the no
      signaling condition it suggests that the amount of accessible information must
      not be larger than the amount of transmitted information. Here we study this
      principle experimentally in the classical, quantum and post-quantum regimes. We
      simulate correlations that are stronger than allowed by quantum mechanics by
      exploiting the effect of polarization-dependent loss in a photonic Bell-test
      experiment. Our method also applies to other fundamental principles and our
      results highlight the special importance of anisotropic regions of the no
      signalling polytope in the study of fundamental principles. 

PMID- 25378183
TI  - Adrenal responses to a low-dose short synacthen test in children with asthma.
AB  - OBJECTIVES: Corticosteroids are known to cause adrenal suppression. The aim of
      this study was to assess clinical factors affecting responses to a low dose short
      synacthen test (LDSST) in asthmatic children using corticosteroids. DESIGN:
      Patients were recruited from secondary care paediatric asthma populations within
      the UK. PATIENTS: Asthmatic children (5-18 years), receiving corticosteroids,
      underwent a LDSST (n = 525). MEASUREMENTS: Demographics and corticosteroid doses
      were tested for association with baseline and peak (stimulated) cortisol
      concentrations. RESULTS: Baseline cortisol was significantly associated with age
      (log baseline increased 0.04 nm per year of age, P < 0.0001), but not with gender
      or corticosteroid dose. Peak cortisol was significantly associated with total
      corticosteroid cumulative dose (decreased 0.73 nm per 200 mcg/day, P < 0.001) but
      not with age, gender inhaled/intranasal corticosteroid cumulative dose or number
      of courses of rescue corticosteroids. Biochemically impaired response (peak
      cortisol <=500 nm) occurred in 37.0% (161/435) overall, including children using
      GINA low (200-500 mcg/day beclomethasone-CFC equivalent 32%, n = 60), medium (501
      1000 mcg/day (33%, n = 57) and high (>1000 mcg/day 40%, n = 13) doses of inhaled
      corticosteroid (ICS) similarly, and 36.6% of those using fluticasone ICS >=500
      mcg/day (71/194). Impaired response was more frequent in patients on regular oral
      corticosteroids (66%, n = 27, P < 0.001). CONCLUSION: Children with asthma can
      develop biochemical adrenal suppression at similar frequencies for all ICS
      preparations and doses. The clinical consequence of biochemical suppression needs
      further study.

PMID- 25378184
TI  - Commentary on: Draper P. (2014) Editorial: a critique of concept analysis.
      Journal of Advanced Nursing 70, 1207-1208.

PMID- 25378185
TI  - The baby and the bathwater.

PMID- 25378186
TI  - Response to two JAN Forum commentaries on A critique of concept analysis, P.
      Draper, (2014). Journal of Advanced Nursing, 70: 1207-1208.

PMID- 25378188
TI  - High Plasticity and Substantial Deformation in Nanocrystalline NiFe Alloys Under
      Dynamic Loading.
AB  - A nanocrystalline (NC) NiFe alloy is presented, in which both highly improved
      plasticity and strength are achieved by the dynamic-loading-induced deformation
      mechanisms of de-twinning (that is, reduction of twin density) and significant
      grain coarsening. This work highlights potential ingenious avenues to exploit the
      superior behavior of NC materials under extreme conditions. 

PMID- 25378189
TI  - Regional differences in postneonatal childhood mortality in Finland, 1985-2004.
AB  - AIM: The Finnish healthcare system will undergo a major reform in the near
      future. This study examined whether postneonatal childhood mortality differed
      between university and central hospital districts in Finland from 1985 to 2004
      and whether the causes of death were preventable. METHODS: We analysed
      postneonatal childhood mortality in Finland during two 10-year periods - 1985 to
      1994 and 1995 to 2004 - analysing university and central hospital districts
      separately, as paediatric intensive care is centralised in university hospitals.
      The study looked at the main causes of death in each hospital, and the mortality
      rates were adjusted to demonstrate how many children were at risk of dying.
      RESULTS: Postneonatal childhood mortality decreased during the study period in
      university and central hospital districts. We found no significant difference in
      mortality rates between university hospital districts, but regional differences
      were notable in central hospital districts, partly because of historical
      differences in mortality. Accidents were the most common cause of death, with
      substantial regional differences. CONCLUSION: Regional postneonatal childhood
      mortality differed across central hospital districts, and this should be taken
      into account in the forthcoming restructuring of the Finnish healthcare system.
      Special attention is needed to prevent accidental deaths, both nationally and
      locally.

PMID- 25378190
TI  - Stopped extracorporeal circulation without alarm call due to voltage regulator
      failure.

PMID- 25378195
TI  - The capacity to cope with climate warming declines from temperate to tropical
      latitudes in two widely distributed Eucalyptus species.
AB  - As rapid climate warming creates a mismatch between forest trees and their home
      environment, the ability of trees to cope with warming depends on their capacity
      to physiologically adjust to higher temperatures. In widespread species,
      individual trees in cooler home climates are hypothesized to more successfully
      acclimate to warming than their counterparts in warmer climates that may approach
      thermal limits. We tested this prediction with a climate-shift experiment in
      widely distributed Eucalyptus tereticornis and E. grandis using provenances
      originating along a ~2500 km latitudinal transect (15.5-38.0 degrees S) in
      eastern Australia. We grew 21 provenances in conditions approximating summer
      temperatures at seed origin and warmed temperatures (+3.5  degrees C) using a
      series of climate-controlled glasshouse bays. The effects of +3.5  degrees C
      warming strongly depended on home climate. Cool-origin provenances responded to
      warming through an increase in photosynthetic capacity and total leaf area,
      leading to enhanced growth of 20-60%. Warm-origin provenances, however, responded
      to warming through a reduction in photosynthetic capacity and total leaf area,
      leading to reduced growth of approximately 10%. These results suggest that there
      is predictable intraspecific variation in the capacity of trees to respond to
      warming; cool-origin taxa are likely to benefit from warming, while warm-origin
      taxa may be negatively affected. 

PMID- 25378196
TI  - Nonrandom point defect configurations and driving force transitions for grain
      boundary segregation in trivalent cation doped ZrO2.
AB  - The energetically favorable spatial configuration of M(3+) ions and oxide-ion
      vacancies near a symmetrical grain boundary (GB) in cubic zirconia is determined
      for various trivalent species M(3+) (M = Al, Sc, Y, Gd, La), and the driving
      force for grain boundary segregation (GBS) quantitatively examined using
      atomistic Monte Carlo simulations in conjunction with static lattice
      calculations. For a high concentration of ~10 mol %, it is found that point
      defects near a GB plane preferentially occupy specific sites to minimize total
      lattice energy, rather than being randomly distributed. Systematic analysis shows
      that energetically stable configurations of segregants vary depending on their
      ionic radii. Analysis of the driving force for GBS as a function of dopant
      concentration reveals that three important factors govern GBS. First, occupation
      of specific sites by point defects is necessary to minimize the total lattice
      energy; enrichment of point defects near the GB plane with random configuration
      does not decrease the total lattice energy significantly because of strong
      Coulombic interactions. Second, the factors governing GBS change with increasing
      dopant concentration. At dilute concentrations, relief of bond strain is the
      dominant factor, while at high concentrations Coulombic interactions, which
      depend strongly on the specific arrangement of defects, become another dominant
      factor. Third, the stabilization of matrix cations, Zr(4+) ions, is the dominant
      factor to lower the driving force for GBS at all concentrations. In contrast, the
      stabilization of M(3+) ions does not necessarily contribute to GBS of point
      defects at high concentrations. These findings suggest practical ways to control
      GBS to enhance materials' properties or minimize detrimental effects. 

PMID- 25378197
TI  - Membranes with fast and selective gas-transport channels of laminar graphene
      oxide for efficient CO2 capture.
AB  - Graphene oxide (GO) nanosheets were engineered to be assembled into laminar
      structures having fast and selective transport channels for gas separation. With
      molecular-sieving interlayer spaces and straight diffusion pathways, the GO
      laminates endowed as-prepared membranes with excellent preferential CO2
      permeation performance (CO2 permeability: 100 Barrer, CO2/N2 selectivity: 91) and
      extraordinary operational stability (>6000 min), which are attractive for
      implementation of practical CO2 capture.

PMID- 25378198
TI  - Chiral 1,2-dialkenyl diaziridines: synthesis, enantioselective separation, and
      nitrogen inversion barriers.
AB  - trans-1,2-Disubstituted diaziridines form stable enantiomers at ambient
      conditions because of the two stereogenic pyramidal nitrogen atoms.
      Functionalized trans-1,2-disubstituted diaziridines can be utilized as a chiral
      switching moiety between two enantiomeric states in more complex molecular
      structures. However, the synthesis of functionalized diaziridines is quite
      challenging, because of the limited tolerance of reaction conditions that can be
      applied. Here we present a strategy to make trans-1,2-disubstituted diaziridines
      accessible as versatile building blocks in C-C-bond formations, i.e., the Heck
      reaction, and therefore introducing aryl substituents. The synthesis of trans-1,2
      dialkenyl diaziridines with terminal alkenyl substituents and their stereodynamic
      properties are described.

PMID- 25378199
TI  - Variable electrobehavioral patterns during focal nonconvulsive status epilepticus
      induced by unilateral intrahippocampal injection of kainic acid.
AB  - OBJECTIVE: Nonconvulsive status epilepticus (ncSE) is a severe condition that may
      result in neurologic sequelae and epilepsy resistant to pharmacologic treatment.
      We analyze here seizure and electroencephalography (EEG) patterns and their
      correlation to the development of a chronic epileptic condition in a guinea pig
      model of focal ncSE induced by intrahippocampal injection of kainic acid (KA).
      METHODS: Electrobehavioral patterns during ncSE induced by unilateral injection
      of 1 MUg of KA in the CA1 region of the hippocampus were characterized by
      continuous video-EEG monitoring in 13 guinea pigs bilaterally implanted with
      recording electrodes in the hippocampus and neocortex. RESULTS: Video-EEG
      analysis demonstrates a high variability of seizure type and duration during KA
      induced ncSE. Seizures showed focal signs correlated with diverse epileptiform
      EEG discharge distributions, either diffuse or localized. Nonfocal (bilateral
      motor) signs during seizures most likely correlated with a diffuse EEG pattern.
      The evolution into a chronic epileptic condition correlated neither with the
      severity of seizure pattern nor with the diffusion of the EEG discharges observed
      during the ncSE. SIGNIFICANCE: Video-EEG monitoring in a guinea pig model of ncSE
      induced by unilateral hippocampal injection of KA demonstrates a high variability
      of electrobehavioral patterns. We demonstrate that the seizure severity score
      during focal ncSE is not a predictor of the evolution into a chronic epileptic
      condition of mesial temporal lobe epilepsy.

PMID- 25378200
TI  - Refolding and simultaneous purification of recombinant human proinsulin from
      inclusion bodies on protein-folding liquid-chromatography columns.
AB  - Protein-folding liquid chromatography (PFLC) is an effective and scalable method
      for protein renaturation with simultaneous purification. However, it has been a
      challenge to fully refold inclusion bodies in a PFLC column. In this work,
      refolding with simultaneous purification of recombinant human proinsulin (rhPI)
      from inclusion bodies from Escherichia coli were investigated using the surface
      of stationary phases in immobilized metal ion affinity chromatography (IMAC) and
      high-performance size-exclusion chromatography (HPSEC). The results indicated
      that both the ligand structure on the surface of the stationary phase and the
      composition of the mobile phase (elution buffer) influenced refolding of rhPI.
      Under optimized chromatographic conditions, the mass recoveries of IMAC column
      and HPSEC column were 77.8 and 56.8% with purifies of 97.6 and 93.7%,
      respectively. These results also indicated that the IMAC column fails to refold
      rhPI, and the HPSEC column enables efficient refolding of rhPI with a low-urea
      gradient-elution method. The refolded rhPI was characterized by circular
      dichroism spectroscopy. The molecular weight of the converted human insulin was
      further confirmed with SDS-18% PAGE, Matrix-Assisted Laser Desorption/ Ionization
      Time of Flight Mass Spectrometry (MALDI-TOF-MS) and the biological activity assay
      by HP-RPLC.

PMID- 25378201
TI  - Immersive visualization for enhanced computational fluid dynamics analysis.
AB  - Modern biomedical computer simulations produce spatiotemporal results that are
      often viewed at a single point in time on standard 2D displays. An immersive
      visualization environment (IVE) with 3D stereoscopic capability can mitigate some
      shortcomings of 2D displays via improved depth cues and active movement to
      further appreciate the spatial localization of imaging data with temporal
      computational fluid dynamics (CFD) results. We present a semi-automatic workflow
      for the import, processing, rendering, and stereoscopic visualization of high
      resolution, patient-specific imaging data, and CFD results in an IVE. Versatility
      of the workflow is highlighted with current clinical sequelae known to be
      influenced by adverse hemodynamics to illustrate potential clinical utility. 

PMID- 25378202
TI  - CNS intravascular large cell lymphoma in a patient with autoimmune hemolytic
      anemia.
AB  - Intravascular large cell lymphoma (IVLCL) is a rare disease characterized by
      proliferation of malignant lymphocytes within the small blood vessel lumens. The
      association of IVLCL with autoimmune hemolytic anemia (AIHA) has been described
      in a single case report, but the true prevalence of this co-occurrence is not
      known because of declining autopsy rates. Here, we report a case of a 41-year-old
      woman who carried a diagnosis of AIHA for 2 years, with repeated hemolytic
      episodes that were initially well controlled with immunomodulatory treatment. At
      her last presentation, the patient developed rapidly progressive neurologic
      symptoms and leukoencephalopathy on MRI; she died 4 weeks later with a clinical
      impression of thrombotic microangiopathy, a known complication of AIHA. At
      autopsy, the brain showed widespread platelet thrombi and intraparenchymal
      hemorrhages characteristic of this disorder. In addition, there was evidence of a
      clinically unsuspected IVLCL, most likely of B-cell lineage. This case
      illustrates a potential association between IVLCL and AIHA, highlights the need
      for broad differential diagnosis in cases with atypical disease presentation or
      progression, and underlines the importance of autopsy in establishing the full
      cause of morbidity and mortality.

PMID- 25378203
TI  - 25-hydroxyvitamin D3 status is associated with developing adaptive and innate
      immune responses in the first 6 months of life.
AB  - BACKGROUND: Vitamin D (25[OH]D3) status in early life has been linked to the risk
      of allergic disease in multiple observational studies. While immunomodulating
      properties are well recognized, there are few longitudinal studies of 25(OH)D3
      status, immune function and allergic disease in infants. OBJECTIVE: To
      investigate 25(OH)D3 levels at birth [cord blood (CB)] and at 6 months of age in
      relation to immune function at 6 months of age, and clinical outcomes up to 30
      months of age in infants with a maternal history of atopy. METHODS: In a subset
      of infants (n = 225) enrolled in a RCT (ACTRN12606000281594), 25(OH)D3 levels
      were assessed in relation to peripheral blood mononuclear cell cytokine responses
      to house dust mite (HDM), ovalbumin (OVA) and beta-lactoglobulin allergens, or
      Toll-like receptor (TLR) ligands (lipopolysaccharide, lipoteichoic acid,
      polyinosinic : polycytidylic acid and CpG oligonucleotide) at 6 months of age, in
      addition to clinical outcomes (eczema, wheeze and allergen sensitisation) up to
      30 months of age. RESULTS: Infants with higher 25(OH)D3 at birth (>= 75 nmol/L,
      compared with < 50 nmol/L) had lower IL-5 and IL-13 responses to HDM by 6 months
      (P < 0.001 and P = 0.003, respectively). This was also reflected in strong
      inverse correlations between CB 25(OH)D3 levels and HDM IL-13 (rho = -0.57; P =
      0.0002) and IL-5 (rho = -0.59, P = 0.0001) responses, with a similar trend for IL
      5 (rho = -0.29; P = 0.009) responses to OVA. For innate stimulations, higher
      25(OH)D3 levels at 6 months were associated with greater responses to TLR
      ligands. Additionally, higher CB 25(OH)D3 was associated with reduced risk eczema
      at 6 months (P = 0.011) and 12 months (P = 0.034). CONCLUSION: This suggests that
      improving 25(OH)D3 status in pregnancy or early infancy may reduce the
      development of allergic disease in high-risk infants by inhibiting cytokine
      profiles associated with allergy. Results of clinical trials are awaited to
      determine the efficacy of vitamin D supplementation in allergy prevention.

PMID- 25378205
TI  - Pharmacokinetics and pharmacodynamics following intravenous administration of
      recombinant human hepatocyte growth factor in rats with renal injury.
AB  - BACKGROUND/AIM: Hepatocyte growth factor (HGF) plays a role in the regeneration
      and protection of the kidney, but little information is available concerning the
      pharmacokinetics of therapeutic treatment with HGF. In this study, HGF was
      administered after the onset of renal injury, and pharmacokinetic analysis was
      performed simultaneously with an efficacious dose. METHODS: For the study of
      pharmacodynamics, recombinant human HGF was intravenously administered to rats
      with glycerol-induced acute kidney injury (AKI). In the pharmacokinetic study,
      rats subjected to glycerol injection or renal ischemia-reperfusion were used as
      models of AKI, and rats subjected to 5/6 nephrectomy were used as models of
      chronic kidney disease (CKD). RESULTS: After intravenous administration of HGF at
      doses of 0.5-2.0 mg/kg, the elevation of blood urea nitrogen was suppressed,
      indicating that HGF had a pharmacodynamic effect. However, no significant
      difference was seen in the pharmacokinetic parameters such as clearance,
      distribution volume and half-life between the normal, AKI and CKD groups.
      CONCLUSION: The intravenous administration of HGF after the onset of renal
      dysfunction exerted a pharmacological effect on AKI, and renal injury did not
      affect the clearance of plasma HGF. This unaffected profile may serve as a base
      for the safety of HGF during therapeutic administration.

PMID- 25378206
TI  - Case report: concurrent Wilson disease and Huntington disease: lightning can
      strike twice.

PMID- 25378207
TI  - Return to play and recurrent instability after in-season anterior shoulder
      instability: a prospective multicenter study.
AB  - BACKGROUND: There is no consensus on the optimal treatment of in-season athletes
      with anterior shoulder instability, and limited data are available to guide
      return to play. PURPOSE: To examine the likelihood of return to sport and the
      recurrence of instability after an in-season anterior shoulder instability event
      based on the type of instability (subluxation vs dislocation). Additionally,
      injury factors and patient-reported outcome scores administered at the time of
      injury were evaluated to assess the predictability of eventual successful return
      to sport and time to return to sport during the competitive season. STUDY DESIGN:
      Cohort study (prognosis); Level of evidence, 2. METHODS: Over 2 academic years,
      45 contact intercollegiate athletes were prospectively enrolled in a multicenter
      observational study to assess return to play after in-season anterior
      glenohumeral instability. Baseline data collection included shoulder injury
      characteristics and shoulder-specific patient-reported outcome scores at the time
      of injury. All athletes underwent an accelerated rehabilitation program without
      shoulder immobilization and were followed during their competitive season to
      assess the success of return to play and recurrent instability. RESULTS: Thirty
      three of 45 (73%) athletes returned to sport for either all or part of the season
      after a median 5 days lost from competition (interquartile range, 13). Twelve
      athletes (27%) successfully completed the season without recurrence. Twenty-one
      athletes (64%) returned to in-season play and had subsequent recurrent
      instability including 11 recurrent dislocations and 10 recurrent subluxations. Of
      the 33 athletes returning to in-season sport after an instability event, 67%
      (22/33) completed the season. Athletes with a subluxation were 5.3 times more
      likely (odds ratio [OR], 5.32; 95% CI, 1.00-28.07; P = .049) to return to sport
      during the same season when compared with those with dislocations. Logistic
      regression analysis suggests that the Western Ontario Shoulder Instability Index
      (OR, 1.05; 95% CI, 1.00-1.09; P = .037) and Simple Shoulder Test (OR, 1.03; 95%
      CI, 1.00-1.05; P = .044) administered after the initial instability event are
      predictive of the ability to return to play. Time loss from sport after a
      shoulder instability event was most strongly and inversely correlated with the
      Simple Shoulder Test (P = .007) at the time of initial injury. CONCLUSION: In the
      largest prospective study evaluating shoulder instability in in-season contact
      athletes, 27% of athletes returned to play and completed the season without
      subsequent instability. While the majority of athletes who return to sport
      complete the season, recurrent instability events are common regardless of
      whether the initial injury was a subluxation or dislocation.

PMID- 25378208
TI  - Effect of accelerated weightbearing after matrix-associated autologous
      chondrocyte implantation on the femoral condyle: a prospective, randomized
      controlled study presenting MRI-based and clinical outcomes after 5 years.
AB  - BACKGROUND: Long-term effects of different weightbearing (WB) modalities after
      matrix-associated autologous chondrocyte implantation (MACI) on changes in knee
      articular cartilage and clinical outcomes are needed to establish more evidence
      based recommendations for postoperative rehabilitation. HYPOTHESIS: There will be
      no differences between accelerated WB compared with delayed WB regarding knee
      articular cartilage or patient self-reported knee function or activity level 5
      years after MACI. Furthermore, significant correlations between magnetic
      resonance imaging (MRI)-based outcomes and patient-reported outcome measures 5
      years postoperatively will exist. STUDY DESIGN: Randomized controlled trial;
      Level of evidence, 1. METHODS: After MACI, 31 patients (23 male, 8 female) were
      randomly assigned to the accelerated WB group (AWB group) or to the delayed WB
      group (DWB group). With the exception of time and increase to full WB, both
      groups underwent the same rehabilitation program. The AWB group was allowed full
      WB after 6 weeks and the DWB group after 10 weeks. Assessments were performed 3
      months, 2 years, and 5 years postoperatively, but this long-term follow-up study
      only included changes from 2 to 5 years postoperatively. The magnetic resonance
      observation of cartilage repair tissue (MOCART) score (primary outcome), the MRI
      based variables of bone edema and effusion, the Knee Injury and Osteoarthritis
      Outcome Score (KOOS), and the Tegner scale were included. In addition, the
      association between MRI-based outcomes and the KOOS at 5 years postoperatively
      was investigated. RESULTS: There was a significant decrease in the MOCART score
      and a significant increase in bone edema 2 and 5 years postoperatively but no
      significant group differences. The only significant correlation between the MRI
      based variables and the KOOS was found for bone edema and the KOOS subscale of
      pain (r=-0.435, P<.05) at 5-year follow-up. CONCLUSION: There were no significant
      differences in the MRI-based or clinical outcomes between the AWB group and DWB
      group 5 years after MACI. While the clinical outcomes remained stable, a decline
      of the MRI-based findings was observed between 2 and 5 years postoperatively.
      Furthermore, a significant association between bone edema and pain was found. No
      occurrence of unintended effects was observed.

PMID- 25378209
TI  - Use of PET/CT instead of CT-only when planning for radiation therapy does not
      notably increase life years lost in children being treated for cancer.
AB  - BACKGROUND: PET/CT may be more helpful than CT alone for radiation therapy
      planning, but the added risk due to higher doses of ionizing radiation is
      unknown. OBJECTIVE: To estimate the risk of cancer induction and mortality
      attributable to the [F-18]2-fluoro-2-deoxyglucose (FDG) PET and CT scans used for
      radiation therapy planning in children with cancer, and compare to the risks
      attributable to the cancer treatment. MATERIALS AND METHODS: Organ doses and
      effective doses were estimated for 40 children (2-18 years old) who had been
      scanned using PET/CT as part of radiation therapy planning. The risk of inducing
      secondary cancer was estimated using the models in BEIR VII. The prognosis of an
      induced cancer was taken into account and the reduction in life expectancy, in
      terms of life years lost, was estimated for the diagnostics and compared to the
      life years lost attributable to the therapy. Multivariate linear regression was
      performed to find predictors for a high contribution to life years lost from the
      radiation therapy planning diagnostics. RESULTS: The mean contribution from PET
      to the effective dose from one PET/CT scan was 24% (range: 7-64%). The average
      proportion of life years lost attributable to the nuclear medicine dose component
      from one PET/CT scan was 15% (range: 3-41%). The ratio of life years lost from
      the radiation therapy planning PET/CT scans and that of the cancer treatment was
      on average 0.02 (range: 0.01-0.09). Female gender was associated with increased
      life years lost from the scans (P < 0.001). CONCLUSION: Using FDG-PET/CT instead
      of CT only when defining the target volumes for radiation therapy of children
      with cancer does not notably increase the number of life years lost attributable
      to diagnostic examinations.

PMID- 25378211
TI  - Multimodal and multiplex spectral imaging of rat cornea ex vivo using a white
      light laser source.
AB  - We applied our multimodal nonlinear spectral imaging microscope to the
      measurement of rat cornea. We successfully obtained multiple nonlinear signals of
      coherent anti-Stokes Raman scattering (CARS), third-order sum frequency
      generation (TSFG), and second harmonic generation (SHG). Depending on the
      nonlinear optical processes, the cornea tissue was visualized with different
      image contrast mechanism simultaneously. Due to white-light laser excitation,
      multiplex CARS and TSFG spectra were obtained. Combined multimodal and spectral
      analysis clearly elucidated the layered structure of rat cornea with molecular
      structural information. This study indicates that our multimodal nonlinear
      spectral microscope is a promising bioimaging method for tissue study. Multimodal
      nonlinear spectral images of rat cornea at corneal epithelium and corneal stroma
      in the in-plane (XY) direction. With use of the combinational analysis of
      different nonlinear optical processes, detailed molecular structural information
      is available without staining or labelling. 

PMID- 25378210
TI  - Outcomes in children with deep vein thrombosis managed with percutaneous
      endovascular thrombolysis.
AB  - BACKGROUND: Our center has developed a multidisciplinary approach to percutaneous
      endovascular thrombolysis with the goal of improving outcomes in children with
      thrombosis. There is little data describing the safety and efficacy of
      endovascular thrombolysis and the frequency of post-thrombotic syndrome after
      thrombolysis in children. OBJECTIVE: Retrospective analysis of children
      undergoing percutaneous endovascular thrombolysis to determine (1) the safety and
      efficacy of this procedure and (2) the frequency of the diagnosis of post
      thrombotic syndrome after thrombolysis. MATERIALS AND METHODS: We reviewed the
      medical and imaging databases for children who underwent percutaneous
      endovascular thrombolysis for deep venous thrombosis (DVT) between November 2008
      and June 2013 at our institution. Demographic data were reviewed for the
      technical success and complications of thrombolysis and the last assigned post
      thrombotic syndrome score using standardized scoring tools. RESULTS: Forty-one
      children ages 3 months to 21 years (median age: 15 years; 44% male) underwent
      percutaneous endovascular thrombolysis between November 2008 and June 2013. Upper
      extremity DVT occurred in 13 patients (32%); lower extremity DVT occurred in 28
      patients (68%). All 41 patients received thrombolysis grading; 90% of those
      patients achieved greater than 50% thrombus lysis. Twenty-eight patients received
      formal post-thrombotic syndrome scoring and 4 (14%) met diagnostic criteria for
      post-thrombotic syndrome. One major bleeding episode and one pulmonary embolism
      occurred with no long-term sequelae. CONCLUSION: Endovascular thrombolysis for
      DVT in children is safe, effective at thrombus removal and may reduce the
      incidence of post-thrombotic syndrome. Randomized or larger clinical trials would
      be needed to determine the long-term benefits of endovascular thrombolysis.

PMID- 25378212
TI  - Vaccine-preventable travel health risks: what is the evidence--what are the gaps?
AB  - BACKGROUND: Existing travel health guidelines are based on a variety of data with
      underpinning evidence ranging from high-quality randomized controlled trials to
      best estimates from expert opinion. For strategic guidance and to set overall
      priorities, data about average risk are useful. The World Health Organization
      (WHO) plans to base future editions of "International Travel and Health" on its
      new "Handbook for Guideline Development." METHODS: Based on a systematic search
      in PubMed, the existing evidence and quality of data on vaccine-preventable
      disease (VPD) risks in travelers was examined and essentials of vaccine efficacy
      were briefly reviewed. The Grading of Recommendations, Assessment, Development
      and Evaluation (GRADE) framework was used to evaluate the quality of the data.
      RESULTS: Moderate-quality data to determine the risk of VPD exist on those that
      are frequently imported, whereas in most others the level of confidence with
      existing data is low or very low. CONCLUSIONS: In order for the WHO to produce
      graded risk statements in the updated version of "International Travel and
      Health," major investment of time plus additional high-quality, generalizable
      risk data are needed.

PMID- 25378213
TI  - Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the
      generation of behavioral preferences for cue-directed food choices.
AB  - BACKGROUND: Behavioral choices in habits and innate behaviors occur automatically
      in the absence of conscious selection. These behaviors are not easily modified by
      learning. Similar types of behaviors also occur in various mental illnesses
      including drug addiction, obsessive-compulsive disorder, schizophrenia, and
      autism. However, underlying mechanisms are not clearly understood. In the present
      study, we investigated the molecular mechanisms regulating unconditioned
      preferred behaviors in food-choices. RESULTS: Mice lacking adenylyl cyclase-5
      (AC5 KO mice), which is preferentially expressed in the dorsal striatum, consumed
      food pellets nearly one after another in cages. AC5 KO mice showed aversive
      behaviors to bitter tasting quinine, but they compulsively chose quinine
      containing AC5 KO-pellets over fresh pellets. The unusual food-choice behaviors
      in AC5 KO mice were due to the gain of behavioral preferences for food pellets
      containing an olfactory cue, which wild-type mice normally ignored. Such food
      choice behaviors in AC5 KO mice disappeared when whiskers were trimmed.
      Conversely, whisker trimming in wildtype mice induced behavioral preferences for
      AC5 KO food pellets, indicating that preferred food-choices were not learned
      through prior experience. Both AC5 KO mice and wildtype mice with trimmed
      whiskers had increased glutamatergic input from the barrel cortex into the dorsal
      striatum, resulting in an increase in the mGluR1-dependent signaling cascade. The
      siRNA-mediated inhibition of mGluR1 in the dorsal striatum in AC5 KO mice and
      wildtype mice with trimmed whiskers abolished preferred choices for AC5 KO food
      pellets, whereas siRNA-mediated inhibition of mGluR3 glutamate receptors in the
      dorsal striatum in wildtype mice induced behavioral preferences for AC5 KO food
      pellets, thus mimicking AC5 KO phenotypes. CONCLUSIONS: Our results show that the
      gain and loss of behavioral preferences for a specific cue-directed option were
      regulated by specific cellular factors in the dorsal striatum, such that the
      preferred food choices were switched on when either the mGluR3-AC5 pathway was
      inactive or the mGluR1 pathway was active, whereas the preferred food-choices
      were switched off when mGluR1 or its downstream pathway was suppressed. These
      results identify the AC5 and mGluR system in the dorsal striatum as molecular
      on/off switches to direct decisions on behavioral preferences for cue-oriented
      options.

PMID- 25378214
TI  - Local and systemic toxicity of Echis carinatus venom: neutralization by Cassia
      auriculata L. leaf methanol extract.
AB  - Viper bites cause high morbidity and mortality especially in tropical and
      subtropical regions, affecting a large number of the rural population in these
      areas. Even though anti-venoms are available, in most cases they fail to tackle
      viper venom-induced local manifestations that persist even after anti-venom
      administration. Several studies have been reported the use of plant products and
      approved drugs along side anti-venom therapy for efficient management of local
      tissue damage. In this regard, the present study focuses on the protective
      efficacy of Cassia auriculata L. (Leguminosae) against Echis carinatus venom
      (ECV) induced toxicity. C. auriculata is a traditional medicinal plant, much
      valued in alternative medicine for its wide usage in ayurveda, naturopathy, and
      herbal therapy. Further, it has been used widely by traditional healers for
      treatment of snake and scorpion bites in the Western Ghats of Karnataka, India.
      In the present study, C. auriculata leaf methanol extract (CAME) significantly
      inhibited enzymatic activities of ECV proteases (96 +/- 1 %; P = 0.001), PLA2 (45
      +/- 5 %; P = 0.01) and hyaluronidases (100 %; P = 0.0003) in vitro and
      hemorrhage, edema and myotoxicity in vivo. Further, CAME effectively reduced the
      lethal potency of ECV and increased the survival time of mice by ~6 times (17 vs
      3 h). These inhibitory potentials of CAME towards hydrolytic enzymes, mortal and
      morbid symptoms of ECV toxins clearly substantiates the use by traditional
      healers of C. auriculata as a folk medicinal remedy for snakebite. 

PMID- 25378215
TI  - BIGH3 protein and macrophages in retinal endothelial cell apoptosis.
AB  - Diabetes is a pandemic disease with a higher occurrence in minority populations.
      The molecular mechanism to initiate diabetes-associated retinal angiogenesis
      remains largely unknown. We propose an inflammatory pathway of diabetic
      retinopathy in which macrophages in the diabetic eye provide TGFbeta to retinal
      endothelial cells (REC) in the retinal microvasculature. In response to TGFbeta,
      REC synthesize and secrete a pro-apoptotic BIGH3 (TGFbeta-Induced Gene Human
      Clone 3) protein, which acts in an autocrine loop to induce REC apoptosis. Rhesus
      monkey retinal endothelial cells (RhREC) were treated with dMCM (cell media of
      macrophages treated with high glucose and LDL) and assayed for apoptosis (TUNEL),
      BIGH3 mRNA (qPCR), and protein (Western blots) expressions. Cells were also
      treated with TauGFbeta1 and 2 for BIGH3 mRNA and protein expression. Inhibition
      assays were carried out using antibodies for TGFbeta1 and for BIGH3 to block
      apoptosis and mRNA expression. BIGH3 in cultured RhREC cells were identified by
      immunohistochemistry (IHC). Distribution of BIGH3 and macrophages in the diabetic
      mouse retina was examined with IHC. RhRECs treated with dMCM or TGFbeta showed a
      significant increase in apoptosis and BIGH3 protein expression. Recombinant BIGH3
      added to RhREC culture medium led to a dose-dependent increase in apoptosis.
      Antibodies (Ab) directed against BIGH3 and TGFbeta, as well as TGFbeta receptor
      blocker resulted in a significant reduction in apoptosis induced by either dMCM,
      TGFbeta or BIGH3. IHC showed that cultured RhREC constitutively expressed BIGH3.
      Macrophage and BIGH3 protein were co-localized to the inner retina of the
      diabetic mouse eye. Our results support a novel inflammatory pathway for diabetic
      retinopathy. This pathway is initiated by TGFbeta released from macrophages,
      which promotes synthesis and release of BIGH3 protein by REC and REC apoptosis. 

PMID- 25378216
TI  - Oxygen-induced plasticity in tracheal morphology and discontinuous gas exchange
      cycles in cockroaches Nauphoeta cinerea.
AB  - The function and mechanism underlying discontinuous gas exchange in terrestrial
      arthropods continues to be debated. Three adaptive hypotheses have been proposed
      to explain the evolutionary origin or maintenance of discontinuous gas exchange
      cycles (DGCs), which may have evolved to reduce respiratory water loss,
      facilitate gas exchange in high CO2 and low O2 micro-environments, or to
      ameliorate potential damage as a result of oversupply of O2. None of these
      hypotheses have unequivocal support, and several non-adaptive hypotheses have
      also been proposed. In the present study, we reared cockroaches Nauphoeta cinerea
      in selected levels of O2 throughout development, and examined how this affected
      growth rate, tracheal morphology and patterns of gas exchange. O2 level in the
      rearing environment caused significant changes in tracheal morphology and the
      exhibition of DGCs, but the direction of these effects was inconsistent with all
      three adaptive hypotheses: water loss was not associated with DGC length,
      cockroaches grew fastest in hyperoxia, and DGCs exhibited by cockroaches reared
      in normoxia were shorter than those exhibited by cockroaches reared in hypoxia or
      hyperoxia. 

PMID- 25378217
TI  - Sex differences in the long-term repeatability of the acute stress response in
      long-lived, free-living Florida scrub-jays (Aphelocoma coerulescens).
AB  - There is increasing evidence that individual differences in the physiological
      stress response are persistent traits in many animals. To test the hypothesis
      that the stress-induced CORT (SI-CORT) response is repeatable over the adult life
      span of Florida scrub-jays (Aphelocoma coerulescens), we sampled 32 male and 25
      female free-living scrub-jays (aged 2-13 years) during a 9-year period (2004
      2012). Each individual was sampled two to five times and samples were collected
      one or more years apart during the pre-breeding season (Jan-March). In addition,
      individuals sampled over the greatest time period (6-8 years) were analyzed
      separately to more closely assess long-term repeatability. SI-CORT was repeatable
      in females, but not males, when values were not corrected for confounding
      variables (agreement repeatability). However, when the year and time of day of
      sample collection were controlled (adjusted repeatability), SI-CORT was
      repeatable in both sexes. SI-CORT was also repeatable in the males and females
      sampled 6-8 years apart. Finally, baseline CORT levels of males, but not females,
      exhibited low but significant repeatability when adjusted for year. The results
      of this study demonstrate that differences in SI-CORT levels were repeatable
      within adult scrub-jays sampled up to 8 years apart. Further, the female SI-CORT
      response was more consistent between pre-breeding seasons than males, which may
      have resulted from males having higher SI-CORT plasticity in response to
      environmental conditions. These data support the hypothesis that the SI-CORT
      response of Florida scrub-jays develops before adulthood and persists throughout
      much, if not all, of their natural adult life span.

PMID- 25378219
TI  - A green approach to offset the perturbation action of 1-butyl-3-methylimidazolium
      iodide on alpha-chymotrypsin.
AB  - Recently, studies have provided evidence for the negative effects of ionic
      liquids (ILs), "greener solvents," on proteins [Phys. Chem. Chem. Phys., 2014,
      16, 5514]. The search to offset the negative effects of ILs on proteins has come
      into limelight as the maintenance of a "green solvent medium" is a great
      challenge for chemists and biochemists. As the first step in this search, 1-butyl
      3-methylimidazolium bromide ([Bmim][Br]) has been applied to offset the
      deleterious action of 1-butyl-3-methylimidazolium iodide ([Bmim][I]) on alpha
      chymotrypsin (CT). Fluorescence and circular dichroism (CD) experiments results
      have indicated that [Bmim][Br] significantly offsets the deleterious action of
      [Bmim][I] at lower concentrations (0.025 M). Surprisingly, the stabilizing action
      of [Bmim][Br] turns into a deleterious action for CT at higher concentrations
      (>0.1 M). On the other hand, [Bmim][I] acted as a destabilizer for CT at all
      investigated concentrations (0.025-0.6 M). The results obtained from this study
      lead to valuable insights into the selection of suitable ILs to attenuate the
      deleterious action of another IL without disturbing the protein structure. 

PMID- 25378218
TI  - Heat loss in air of an Antarctic marine mammal, the Weddell seal.
AB  - The conflicting needs of homeostasis in air versus water complicate our
      understanding of thermoregulation in marine mammals. Large-scale modeling efforts
      directed at predicting the energetic impact of changing sea ice conditions on
      polar ecosystems require a better understanding of thermoregulation in air of
      free-ranging animals. We utilized infrared imaging as an indirect approach to
      determine surface temperatures of dry, hauled-out Weddell seals (Leptonychotes
      weddellii, n = 35) of varying age and body condition during the Antarctic summer.
      The study groups provided a fivefold range in body mass and a threefold range in
      blubber depth. Surface temperature (T s) did not vary by body region (head,
      shoulder, axilla, torso, hip, flippers). Average seal T s (mean 13.9 +/- 11.2 
      degrees C) was best described through a combination of the physical traits of
      body mass and environmental variables of ambient temperature T air, and wind
      speed. Additional factors of ice temperature (T ice), relative humidity and cloud
      cover did not improve the model. Heat transfer model estimates suggested that
      radiation contributed 56.6 +/- 7.7 % of total heat loss. Convection and
      conduction accounted for the remaining 15.7 +/- 12.3 and 27.7 +/- 9.3 %,
      respectively. Heat loss by radiation was primarily influenced by body mass and
      wind speed, whereas convective heat loss was influenced primarily by blubber
      depth and wind speed. Conductive heat loss was modeled largely as a function of
      physical traits of mass and blubber depth rather than any environmental
      covariates, and therefore was substantially higher in animals in leaner
      condition.

PMID- 25378221
TI  - The use of an extract of Hypericum perforatum and Azadirachta indica in a
      neuropathic patient with advanced diabetic foot.
AB  - The successful use of an extract of Hypericum flowers (Hypericum perforatum) and
      nimh oil (Azadirachta indica; Hyperoil) in foot wounds with exposed bone in a
      patient with bilateral advanced diabetic ulcers, has been reported previously. It
      was hypothesised that this amelioration was linked with the improved glycaemic
      control and peripheral microvascular circulation. In this case report, the
      surprisingly successful outcome of another patient using Hyperoil for infection
      damaged diabetic foot, without prior use of surgical procedure, is described. The
      patient had no macrovascular pattern impairment. Diabetic foot healing paralleled
      with controlled local infection and enhanced glycaemic control. The outcome of
      this patient suggests that the effectiveness of this inexpensive therapy using
      Hyperoil for diabetic foot is not only linked with the presence of severe
      microvascular disorder, but also with the appropriate local treatment for ulcer
      being a must for its recovery. 

PMID- 25378222
TI  - Salvaging a solitary necrotic testis in a quadriparetic.

PMID- 25378223
TI  - The 9-point hedonic scale and hedonic ranking in food science: some reappraisals
      and alternatives.
AB  - The 9-point hedonic scale has been used routinely in food science, the same way
      for 60 years. Now, with advances in technology, data from the scale are being
      used for more and more complex programs for statistical analysis and modeling.
      Accordingly, it is worth reconsidering the presentation protocols and the
      analyses associated with the scale, as well as some alternatives. How the brain
      generates numbers and the types of numbers it generates has relevance for the
      choice of measurement protocols. There are alternatives to the generally used
      serial monadic protocol, which can be more suitable. Traditionally, the 'words'
      on the 9-point hedonic scale are reassigned as 'numbers', while other '9-point
      hedonic scales' are purely numerical; the two are not interchangeable. Parametric
      statistical analysis of scaling data is examined critically and alternatives
      discussed. The potential of a promising alternative to scaling itself, simple
      ranking with a hedonic R-Index signal detection analysis, is explored in
      comparison with the 9-point hedonic scale.

PMID- 25378224
TI  - LncRNA and mRNA interaction study based on transcriptome profiles reveals
      potential core genes in the pathogenesis of human glioblastoma multiforme.
AB  - OBJECTIVES: To study the expression profiles of lncRNA and mRNA in glioblastoma
      multiforme (GBM) and to find potential core genes in the pathogenesis of this
      high malignant disease. METHODS: Agilent Microarray (Arrystar v2.0) was used to
      detect the expressions of 33,045 lncRNAs and 30,215 coding transcripts in 5 GBM
      and 5 normal brain samples. Differentially expressed lncRNAs and mRNAs were
      identified through Volcano Plot filtering. The expressions of six lncRNAs were
      further detected by qPCR to validate the results of microarray. The function of
      differential mRNA was determined by pathway and GO analysis, and the function of
      lncRNAs was studied by subgroup analysis and by their physical or functional
      relationships with corresponding mRNAs. RESULTS: A total of 815 lncRNAs and 738
      mRNAs are found to be differentially expressed between the GBM and normal brain
      groups. With the expression of these differentially expressed genes, the two
      group samples could be clearly differentiated. The result of qPCR has showed a
      good consistency with the microarray, thus proving the accuracy of the microarray
      data. GO and Pathway analyses have proved that the functions of differentially
      expressed mRNAs in GBM related closely with many processes that important in the
      cancer pathogenesis. Core lncRNAs and mRNAs that may play important roles in the
      pathogenesis of GBM are revealed and listed according to various methods.
      CONCLUSION: The GBM shows an aberrant expression profile of lncRNA and mRNA.
      Potential core genes are revealed by the lncRNA and mRNA interaction study based
      on transcriptome profiles in GBM.

PMID- 25378225
TI  - An observational, real-life safety study of a 5-grass pollen sublingual tablet in
      children and adolescents.
AB  - BACKGROUND: The safety and efficacy of pre- and coseasonal sublingual allergen
      immunotherapy (SLIT) with a 5-grass pollen sublingual tablet have been
      demonstrated in a randomized clinical trial (RCT) in children and adolescents.
      Observational, 'real-life' studies can usefully complement the results of RCTs.
      METHODS: A prospective, open-label, observational, multicentre post-marketing
      study of children and adolescents (aged 5-17, with grass pollen-induced allergic
      rhinitis) treated with the 5-grass pollen sublingual tablet was performed between
      June 2009 and January 2011 in Germany. Adverse events (AEs) were recorded during
      consultations with the investigating physicians; AEs judged to have at least a
      possible causal link to the tablet were classified as adverse drug reactions
      (ADRs). RESULTS: Eight hundred and forty-nine patients were enrolled (by 207
      investigating physicians), 829 (mean +/- s.d. age: 10.9 +/- 3.3 yr) completed the
      study without major protocol deviations, and 796 were fully documented with
      respect to AEs. Ninety-four of the 796 patients (11.8%) experienced at least one
      ADR on the first day of SLIT and 218 (27.4%) experienced at least one ADR during
      the study. Four hundred and sixty-six of the 596 ADRs (78.2%) were mild or
      moderate. The most common ADRs were throat irritation (19.1% of the reactions),
      oral paresthesia (8.2%), oral pruritus (6.5%) and oedema mouth (6.2%). Serious
      ADRs occurred in five patients. No epinephrine use was reported. Seventy-six of
      the 829 patients (9.2%) discontinued SLIT due to AEs. Tolerability was judged to
      be good or very good by patients (84.7%), parents (87.0%) and investigators
      (89.7%). CONCLUSIONS: In clinical practice, pre- and coseasonal treatment with a
      5-grass pollen sublingual tablet is safe and well tolerated in children and
      adolescents.

PMID- 25378226
TI  - Design and synthesis of a mitochondria-targeting carrier for small molecule
      drugs.
AB  - A novel mitochondria-targeting carrier QCy7HA was developed. QCy7HA transported
      the covalently attached doxorubicin (DOX) to mitochondria specifically. The
      conjugate limited the effects of P-glycoprotein (Pgp) efflux pumps of multidrug
      resistant cells on DOX, indicating that diverting drugs to mitochondria is a
      potential promising method for treatment of drug-resistant cancers. 

PMID- 25378227
TI  - Twist-related protein 1 enhances oral tongue squamous cell carcinoma cell
      invasion through beta-catenin signaling.
AB  - Accumulating evidence suggests that beta-catenin signaling may be involved in
      oral tongue squamous cell carcinoma (OTSCC) cell invasion. Abnormal activation of
      twist-related protein 1 (TWIST1 or TWIST) has been identified in several types of
      human cancer. A recent study showed that overexpression of TWIST is associated
      with a poor prognosis in patients with OTSCC and may enhance OTSCC cell invasion.
      This study investigated the effect of TWIST on beta-catenin signaling in OTSCC
      cells and its impact on OSTCC cell invasion. Stable overexpression of TWIST, with
      or without knockdown of beta-catenin, and stable knockdown of TWIST were
      performed in SCC-4 and TCA8113 human OTSCC cells. Overexpression of TWIST in SCC
      4 and TCA8113 cells increased beta-catenin signaling luciferase reporter
      activity, mRNA levels of the beta-catenin signaling target genes, c-Myc and c-Jun
      levels, soluble beta-catenin level, the phosphorylation status of glycogen
      synthase kinase-3beta (GSK-3beta) at serine 9, matrix metalloproteinase-2 (MMP-2)
      expression and cell invasion. Knockdown of TWIST had the opposite effect. All of
      these changes, with the exception of phosphorylation of GSK-3beta, were
      eliminated by stable knockdown of beta-catenin. In addition, the
      phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002 abrogated the enhancing
      effects of TWIST on mRNA levels of c-Myc and c-Jun, soluble beta-catenin levels,
      MMP-2 expression, cell invasion and GSK-3beta phosphorylation. In conclusion, the
      present study demonstrated that TWIST enhances cell invasion and MMP-2 expression
      in OTSCC cells through beta-catenin signaling, probably via a PI3K-dependent
      mechanism. This study provides novel insights into the molecular mechanisms
      underlying OTSCC progression.

PMID- 25378228
TI  - Rituximab monotherapy as a first-line treatment for pulmonary mucosa-associated
      lymphoid tissue lymphoma.
AB  - Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare extranodal
      lymphoma with a 5-year survival rate of 80-95 %. There is no standard treatment
      strategy for pulmonary MALT lymphoma. In the present study, we performed a
      retrospective evaluation of systemic rituximab monotherapy (375 mg m(-2) day(-1),
      4-8 cycles) as first-line treatment in patients with pulmonary MALT lymphoma. Of
      the eight patients enrolled, five achieved complete response, one achieved
      partial response, and two showed stable disease. Median progression-free survival
      was 66.0 months (range 9.7-87.2 months). Treatment was well tolerated and all
      patients were alive during the median follow-up period of 64.0 months. Rituximab
      monotherapy was efficacious in patients with pulmonary MALT lymphoma,
      demonstrating long-term disease stabilization and symptom reduction. Larger
      prospective studies are warranted to further assess the efficacy of rituximab
      monotherapy. In conclusion, rituximab monotherapy may be considered for first
      line therapy in patients with pulmonary MALT lymphoma.

PMID- 25378229
TI  - Human-inspired feedback synergies for environmental interaction with a dexterous
      robotic hand.
AB  - Effortless control of the human hand is mediated by the physical and neural
      couplings inherent in the structure of the hand. This concept was explored for
      environmental interaction tasks with the human hand, and a novel human-inspired
      feedback synergy (HFS) controller was developed for a robotic hand which
      synchronized position and force feedback signals to mimic observed human hand
      motions. This was achieved by first recording the finger joint motion profiles of
      human test subjects, where it was observed that the subjects would extend their
      fingers to maintain a natural hand posture when interacting with different
      surfaces. The resulting human joint angle data were used as inspiration to
      develop the HFS controller for the anthropomorphic robotic hand, which
      incorporated finger abduction and force feedback in the control laws for finger
      extension. Experimental results showed that by projecting a broader view of the
      tasks at hand to each specific joint, the HFS controller produced hand motion
      profiles that closely mimic the observed human responses and allowed the robotic
      manipulator to interact with the surfaces while maintaining a natural hand
      posture. Additionally, the HFS controller enabled the robotic hand to
      autonomously traverse vertical step discontinuities without prior knowledge of
      the environment, visual feedback, or traditional trajectory planning techniques. 

PMID- 25378231
TI  - Quantum discord as a resource for quantum cryptography.
AB  - Quantum discord is the minimal bipartite resource which is needed for a secure
      quantum key distribution, being a cryptographic primitive equivalent to non
      orthogonality. Its role becomes crucial in device-dependent quantum cryptography,
      where the presence of preparation and detection noise (inaccessible to all
      parties) may be so strong to prevent the distribution and distillation of
      entanglement. The necessity of entanglement is re-affirmed in the stronger
      scenario of device-independent quantum cryptography, where all sources of noise
      are ascribed to the eavesdropper. 

PMID- 25378230
TI  - Redirecting soluble antigen for MHC class I cross-presentation during
      phagocytosis.
AB  - Peptides presented by MHC class I molecules are mostly derived from proteins
      synthesized by the antigen-presenting cell itself, while peptides presented by
      MHC class II molecules are predominantly from materials acquired by endocytosis.
      External antigens can also be presented by MHC class I molecules in a process
      referred to as cross-presentation. Here, we report that mouse dendritic cell (DC)
      engagement to a phagocytic target alters endocytic processing and inhibits the
      proteolytic activities. During phagocytosis, endosome maturation is delayed,
      shows less progression toward the lysosome, and the endocytosed soluble antigen
      is targeted for MHC class I cross-presentation. The antigen processing in these
      arrested endosomes is under the control of NAPDH oxidase associated ROS. We also
      show that cathepsin S is responsible for the generation of the MHC class I
      epitope. Taken together, our results suggest that in addition to solid structure
      uptake, DC phagocytosis simultaneously modifies the kinetics of endosomal
      trafficking and maturation. As a consequence, external soluble antigens are
      targeted into the MHC class I cross-presentation pathway. 

PMID- 25378233
TI  - A two-enzyme immobilization approach using carbon nanotubes/silica as support.
AB  - Multiple enzyme mixtures are attractive for the production of many compounds at
      an industrial level. We report a practical and novel approach for
      coimmobilization of two enzymes. The system consists of a silica microsphere core
      coated with two layers of individually immobilized enzymes. The model enzymes
      alpha-amylase (AA) and glucoamylase (GluA) were individually immobilized on
      carbon nanotubes (CNTs). A CNT-GluA layer was formed by adsorbing CNT-GluA onto
      silica microsphere. A sol-gel layer with entrapped CNT-AA was then formed outside
      the CNT-GluA/silica microsphere conjugate. The coimmobilized alpha-amylase and
      glucoamylase exhibited 95.1% of the activity of the mixture of free alpha-amylase
      and glucoamylase. The consecutive use exhibited a good stability of the
      coimmobilized enzymes. The developed approach demonstrates advantages, including
      controlling the ratio of coimmobilized enzymes in an easy way, facilitating
      diffusion of small molecules in and out of the matrix, and preventing the
      leaching of enzymes.

PMID- 25378232
TI  - B-RafV600E inhibits sodium iodide symporter expression via regulation of DNA
      methyltransferase 1.
AB  - B-RafV600E mutant is found in 40-70% of papillary thyroid carcinoma (PTC) and has
      an important role in the pathogenesis of PTC. The sodium iodide symporter (NIS)
      is an integral plasma membrane glycoprotein that mediates active iodide transport
      into the thyroid follicular cells, and B-RafV600E has been known to be associated
      with the loss of NIS expression. In this study, we found that B-RafV600E
      inhibited NIS expression by the upregulation of its promoter methylation, and
      that specific regions of CpG islands of NIS promoter in B-RafV600E harboring PTC
      were highly methylated compared with surrounding normal tissue. Although DNA
      methyltransferase 3a and 3b (DNMT3a,3b) were not increased by B-RafV600E, DNMT1
      expression was markedly upregulated in PTC and B-RafV600E expressing thyrocytes.
      Furthermore, DNMT1 expression was upregulated by B-RafV600E induced NF-kappaB
      activation. These results led us to conclude that NIS promoter methylation, which
      was induced by B-RafV600E, is one of the possible mechanisms involved in NIS
      downregulation in PTC. 

PMID- 25378234
TI  - Characterization of quantum dot/conducting polymer hybrid films and their
      application to light-emitting diodes.
AB  - Quantum dot/conducting polymer hybrid films are used to prepare light-emitting
      diodes (LEDs). The hybrid films (CdSe@ZnS quantum dots excellently dispersed in a
      conducting polymer matrix, see figure) are readily prepared by various solution
      based processes and are also easily micropatterned. The LEDs exhibit a turn-on
      voltage of 4 V, an external quantum efficiency greater than 1.5%, and almost pure
      green quantum-dot electroluminescence. 

PMID- 25378235
TI  - Hg-contaminated terrestrial spiders pose a potential risk to songbirds at Caddo
      Lake (Texas/Louisiana, USA).
AB  - Methylmercury (MeHg) is an environmental contaminant that can have adverse
      effects on wildlife. Because MeHg is produced by bacteria in aquatic ecosystems,
      studies of MeHg contamination of food webs historically have focused on aquatic
      organisms. However, recent studies have shown that terrestrial organisms such as
      songbirds can be contaminated with MeHg by feeding on MeHg-contaminated spiders.
      In the present study, the authors examined the risk that MeHg-contaminated
      terrestrial long-jawed orb weaver spiders (Tetragnatha sp.) pose to songbirds at
      Caddo Lake (Texas/Louisiana, USA). Methylmercury concentrations in spiders were
      significantly different in river, wetland, and open-water habitats. The authors
      calculated spider-based wildlife values (the minimum spider MeHg concentrations
      causing physiologically significant doses in consumers) to assess exposure risks
      for arachnivorous birds. Methylmercury concentrations in spiders exceeded
      wildlife values for Carolina chickadee (Poecile carolinensis) nestlings, with the
      highest risk in the river habitat. The present study indicates that MeHg
      concentrations in terrestrial spiders vary with habitat and can pose a threat to
      small-bodied nestling birds that consume large amounts of spiders at Caddo Lake.
      This MeHg threat to songbirds may not be unique to Caddo Lake and may extend
      throughout the southeastern United States.

PMID- 25378236
TI  - Sex steroids levels in chronic kidney disease and kidney transplant recipients:
      associations with disease severity and prediction of mortality.
AB  - OBJECTIVE: Our objective was to characterize and evaluate prognostic implications
      of circulating sex steroids in patients at different stages of chronic kidney
      disease (CKD). DESIGN: Prospective observational cohort study. PATIENTS: We
      prospectively recruited patients with CKD III-IV, undergoing chronic dialysis and
      kidney transplant recipients (KTR) from a single centre in 2003-2004.
      MEASUREMENTS: Two stored samples taken 3 months apart were analysed for sex
      hormones using liquid chromatography/tandem mass spectrometry, and the mean of
      the two was used for analysis. We also measured novel biomarkers troponin T and
      NT-proBNP. Patients were followed until death, transplant or 30 June 2013, and
      survival analysis performed. RESULTS: In males, but not in females, both
      testosterone (P = 0.003) as well as oestradiol (P < 0.02) levels were lowest in
      dialysis patients and highest in KTR. Over a median follow up of 8.5 years
      (interquartile range 3.8-9.2), 52 men (36%) died and 24 (17%) received a kidney
      transplant. In Cox proportional hazards regression up to 9.6 years, an increase
      in total testosterone of 1 nmol/l was associated with a 9.8% (95% confidence
      interval 3.1-16.3) decrease in mortality independent of age, body mass index,
      stage of renal disease and circulating levels of NT-proBNP or troponin T. By
      contrast, sex steroid levels were not associated with mortality in females.
      CONCLUSIONS: Testosterone levels differ across stages of kidney disease and low
      testosterone levels predict mortality in males, independent of established and
      novel predictors of mortality.

PMID- 25378237
TI  - Functional characterization and classification of frequent low-density
      lipoprotein receptor variants.
AB  - Familial hypercholesterolemia (FH) is an autosomal-dominant disorder mostly
      caused by mutations in the low-density lipoprotein receptor (LDLR) gene leading
      to increased risk for premature cardiovascular diseases. According to functional
      studies, LDLR mutations may be classified into five classes. The main objective
      of this study was to characterize seven LDLR variants previously detected in FH
      patients. Analysis by flow cytometry and confocal microscopy of LDLR activity
      demonstrate that all the studied variants are pathogenic. Among the mutations
      located in beta-propeller, p.Trp577Gly and p.Ile624del were classified as class
      2, whereas p.Arg416Trp and p.Thr454Asn as class 5. p.Phe800Glyfs*129 (located in
      the cytoplasmic domain), p.Cys155Tyr (located in the binding domain), and
      p.Asn825Lys (inside FxNPxY motif) were classified as class 2, 3, and 4,
      respectively. The results also show that LDLR activity of these class 4 and 5
      variants is not completely abolished, showing a milder phenotype. We have also
      determined that statin response is more efficient lowering total cholesterol in
      heterozygous patients carrying p.Ile624del (class 2) compared with p.Arg416Trp
      and p.Thr454Asn (class 5) variants. In conclusion, these findings emphasize the
      importance of characterizing LDLR pathogenic variants to provide an indisputable
      FH diagnosis and to gain insight into the statin response depending on the LDLR
      class mutation. 

PMID- 25378239
TI  - Psychiatric symptoms induced by hydroxychloroquine.

PMID- 25378238
TI  - Pituitary dysfunction after aneurysmal subarachnoid haemorrhage: course and
      clinical predictors-the HIPS study.
AB  - OBJECTIVE: We describe the occurrence and course of anterior pituitary
      dysfunction (PD) after aneurysmal subarachnoid haemorrhage (SAH), and identify
      clinical determinants for PD in patients with recent SAH. METHODS: We
      prospectively collected demographic and clinical parameters of consecutive
      survivors of SAH and measured fasting state endocrine function at baseline, 6 and
      14 months. We included dynamic tests for growth-hormone function. We used
      logistic regression analysis to compare demographic and clinical characteristics
      of patients with SAH with and without PD. RESULTS: 84 patients with a mean age of
      55.8 (+/-11.9) were included. Thirty-three patients (39%) had PD in one or more
      axes at baseline, 22 (26%) after 6 months and 6 (7%) after 14 months.
      Gonadotropin deficiency in 29 (34%) patients and growth hormone deficiency (GHD)
      in 26 (31%) patients were the most common deficiencies. PD persisted until 14
      months in 6 (8%) patients: GHD in 5 (6%) patients and gonadotropin deficiency in
      4 (5%). Occurrence of a SAH-related complication was associated with PD at
      baseline (OR 2.6, CI 2.2 to 3.0). Hydrocephalus was an independent predictor of
      PD 6 months after SAH (OR 3.3 CI 2.7 to 3.8). PD was associated with a lower
      score on health-related quality of life at baseline (p=0.06), but not at 6 and 14
      months. CONCLUSIONS: Almost 40% of SAH survivors have PD. In a small but
      substantial proportion of patients GHD or gonadotropin deficiency persists over
      time. Hydrocephalus is independently associated with PD 6 months after SAH. TRIAL
      REGISTRATION NUMBER: NTR 2085.

PMID- 25378240
TI  - Diagnosis at your fingertips: splinters and microemboli--is it SLE?

PMID- 25378241
TI  - F3-Isoprostanes as a Measure of in vivo Oxidative Damage in Caenorhabditis
      elegans.
AB  - Oxidative stress has been implicated in the development of a wide variety of
      disease processes, including cardiovascular disease, cancer, and
      neurodegenerative diseases, as well as progressive and normal aging processes.
      Isoprostanes (IsoPs) are prostaglandin-like compounds that are generated in vivo
      from lipid peroxidation of arachidonic acid (AA, C20:4, omega-6) and other
      polyunsaturated fatty acids (PUFA). Since the discovery of IsoPs by Morrow and
      Roberts in 1990, quantification of IsoPs has been shown to be an excellent source
      of biomarkers of in vivo oxidative damage. Eicosapentaenoic acid (EPA, C20:5,
      omega-3) is the most abundant PUFA in Caenorhabditis elegans and gives rise to F3
      IsoPs upon nonenzymatic free-radical-catalyzed lipid peroxidation. The protocol
      presented is the current methodology that our laboratory uses to quantify F3
      IsoPs in C. elegans using gas chromatography/mass spectrometry (GC/MS). The
      methods described herein have been optimized and validated to provide the best
      sensitivity and selectivity for quantification of F3-IsoPs from C. elegans
      lysates.

PMID- 25378243
TI  - Functional binding surface of a beta-hairpin VEGF receptor targeting peptide
      determined by NMR spectroscopy in living cells.
AB  - In this study, the functional interaction of HPLW peptide with VEGFR2 (Vascular
      Endothelial Growth Factor Receptor 2) was determined by using fast (15)N-edited
      NMR spectroscopic experiments. To this aim, (15)N uniformly labelled HPLW has
      been added to Porcine Aortic Endothelial Cells. The acquisition of isotope-edited
      NMR spectroscopic experiments, including (15)N relaxation measurements, allowed a
      precise characterization of the in-cell HPLW epitope recognized by VEGFR2.

PMID- 25378242
TI  - The history and use of human hepatocytes for the treatment of liver diseases: the
      first 100 patients.
AB  - Orthotopic liver transplantation remains the only curative treatment for many end
      stage liver diseases, yet the number of patients receiving liver transplants
      remains limited by the number of organs available for transplant. There is a need
      for alternative therapies for liver diseases. The transplantation of isolated
      hepatocytes (liver cells) has been used as an experimental therapy for liver
      disease in a limited number of cases. Recently, the 100th case of hepatocyte
      transplantation was reported. This review discusses the history of the hepatocyte
      transplant field, the major discoveries that supported and enabled the first
      hepatocyte transplants, and reviews the cases and outcomes of the first 100
      clinical transplants. Some of the problems that limit the application or efficacy
      of hepatocyte transplantation are discussed, as are possible solutions to these
      problems. In conclusion, hepatocyte transplants have proven effective
      particularly in cases of metabolic liver disease where reversal or amelioration
      of the characteristic symptoms of the disease is easily quantified. However, no
      patients have been completely corrected of a metabolic liver disease for a
      significant amount of time by hepatocyte transplantation alone. It is likely that
      future developments in new sources of cells for transplantation will be required
      before this cellular therapy can be fully implemented and available for large
      numbers of patients.

PMID- 25378244
TI  - Rapid and efficient copper-catalyzed Finkelstein reaction of (hetero)aromatics
      under continuous-flow conditions.
AB  - A general, rapid, and efficient method for the copper-catalyzed Finkelstein
      reaction of (hetero)aromatics has been developed using continuous flow to
      generate a variety of aryl iodides. The described method can tolerate a broad
      spectrum of functional groups, including N-H and O-H groups. Additionally, in
      lieu of isolation, the aryl iodide solutions were used in two distinct multistep
      continuous-flow processes (amidation and Mg-I exchange/nucleophilic addition) to
      demonstrate the flexibility of this method. 

PMID- 25378246
TI  - The Transatlantic Trade and Investment Partnership and UK healthcare.

PMID- 25378245
TI  - Motif mismatches in microsatellites: insights from genome-wide investigation
      among 20 insect species.
AB  - We present a detailed genome-wide comparative study of motif mismatches of
      microsatellites among 20 insect species representing five taxonomic orders. The
      results show that varying proportions (~15-46%) of microsatellites identified in
      these species are imperfect in motif structure, and that they also vary in
      chromosomal distribution within genomes. It was observed that the genomic
      abundance of imperfect repeats is significantly associated with the length and
      number of motif mismatches of microsatellites. Furthermore, microsatellites with
      a higher number of mismatches tend to have lower abundance in the genome,
      suggesting that sequence heterogeneity of repeat motifs is a key determinant of
      genomic abundance of microsatellites. This relationship seems to be a general
      feature of microsatellites even in unrelated species such as yeast, roundworm,
      mouse and human. We provide a mechanistic explanation of the evolutionary link
      between motif heterogeneity and genomic abundance of microsatellites by examining
      the patterns of motif mismatches and allele sequences of single-nucleotide
      polymorphisms identified within microsatellite loci. Using Drosophila Reference
      Genetic Panel data, we further show that pattern of allelic variation modulates
      motif heterogeneity of microsatellites, and provide estimates of allele age of
      specific imperfect microsatellites found within protein-coding genes. 

PMID- 25378247
TI  - Scottish NHS comes under strain as budget heads for 1% cut over two years.

PMID- 25378248
TI  - Take-home emergency naloxone to prevent deaths from heroin overdose.

PMID- 25378249
TI  - Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks.
AB  - We introduce a method for simultaneous prediction of microRNA-target interactions
      and their mediated competitive endogenous RNA (ceRNA) interactions. Using high
      throughput validation assays in breast cancer cell lines, we show that our
      integrative approach significantly improves on microRNA-target prediction
      accuracy as assessed by both mRNA and protein level measurements. Our biochemical
      assays support nearly 500 microRNA-target interactions with evidence for
      regulation in breast cancer tumors. Moreover, these assays constitute the most
      extensive validation platform for computationally inferred networks of microRNA
      target interactions in breast cancer tumors, providing a useful benchmark to
      ascertain future improvements. 

PMID- 25378250
TI  - The discovery of integrated gene networks for autism and related disorders.
AB  - Despite considerable genetic heterogeneity underlying neurodevelopmental
      diseases, there is compelling evidence that many disease genes will map to a much
      smaller number of biological subnetworks. We developed a computational method,
      termed MAGI (merging affected genes into integrated networks), that
      simultaneously integrates protein-protein interactions and RNA-seq expression
      profiles during brain development to discover "modules" enriched for de novo
      mutations in probands. We applied this method to recent exome sequencing of 1116
      patients with autism and intellectual disability, discovering two distinct
      modules that differ in their properties and associated phenotypes. The first
      module consists of 80 genes associated with Wnt, Notch, SWI/SNF, and NCOR
      complexes and shows the highest expression early during embryonic development (8
      16 post-conception weeks [pcw]). The second module consists of 24 genes
      associated with synaptic function, including long-term potentiation and calcium
      signaling with higher levels of postnatal expression. Patients with de novo
      mutations in these modules are more significantly intellectually impaired and
      carry more severe missense mutations when compared to probands with de novo
      mutations outside of these modules. We used our approach to define subsets of the
      network associated with higher functioning autism as well as greater severity
      with respect to IQ. Finally, we applied MAGI independently to epilepsy and
      schizophrenia exome sequencing cohorts and found significant overlap as well as
      expansion of these modules, suggesting a core set of integrated
      neurodevelopmental networks common to seemingly diverse human diseases. 

PMID- 25378251
TI  - Race and ancestry in the age of inclusion: technique and meaning in post-genomic
      science.
AB  - This article examines how race and ancestry are taken up in gene-environment
      interaction (GEI) research on complex diseases such as heart disease, diabetes,
      and cancer. Using 54 in-depth interviews of 33 scientists and over 200 hours of
      observation at scientific conferences, we explore how GEI researchers use and
      interpret race, ethnicity, and ancestry in their work. We find that the use of
      self-identified race and ethnicity (SIRE) exists alongside ancestry informative
      markers (AIMs) to ascertain genetic ancestry. Our participants assess the utility
      of these two techniques in relative terms, downplaying the accuracy and value of
      SIRE compared to the precision and necessity of AIMs. In doing so, we argue that
      post-genomic scientists seeking to understand the interactions of genetic and
      environmental disease determinants actually undermine their ability to do so by
      valorizing precise characterizations of individuals' genetic ancestry over
      measurement of the social processes and relations that differentiate social
      groups. 

PMID- 25378252
TI  - Gold nanorods: from synthesis and properties to biological and biomedical
      applications.
AB  - Noble metal nanoparticles are capable of confining resonant photons in such a
      manner as to induce coherent surface plasmon oscillation of their conduction band
      electrons, a phenomenon leading to two important properties. Firstly, the
      confinement of the photon to the nanoparticle's dimensions leads to a large
      increase in its electromagnetic field and consequently great enhancement of all
      the nanoparticle's radiative properties, such as absorption and scattering.
      Moreover, by confining the photon's wavelength to the nanoparticle's small
      dimensions, there exists enhanced imaging resolving powers, which extend well
      below the diffraction limit, a property of considerable importance in potential
      device applications. Secondly, the strongly absorbed light by the nanoparticles
      is followed by a rapid dephasing of the coherent electron motion in tandem with
      an equally rapid energy transfer to the lattice, a process integral to the
      technologically relevant photothermal properties of plasmonic nanoparticles. Of
      all the possible nanoparticle shapes, gold nanorods are especially intriguing as
      they offer strong plasmonic fields while exhibiting excellent tunability and
      biocompatibility. We begin this review of gold nanorods by summarizing their
      radiative and nonradiative properties. Their various synthetic methods are then
      outlined with an emphasis on the seed-mediated chemical growth. In particular, we
      describe nanorod spontaneous self-assembly, chemically driven assembly, and
      polymer-based alignment. The final section details current studies aimed at
      applications in the biological and biomedical fields. 

PMID- 25378253
TI  - Solid waste collection automation in the United States.

PMID- 25378254
TI  - Partnerships for development: municipal solid waste management in Kasese, Uganda.
AB  - Municipal solid waste management systems of many developing countries are
      commonly constrained by factors such as limited financial resources and poor
      governance, making it a difficult proposition to break with complex, entrenched
      and unsustainable technologies and systems. This article highlights strategic
      partnerships as a way to affect a distributed agency among several sets of
      stakeholders to break so-called path dependencies, which occur when such
      unsustainable pathways arise, stabilize and become self-reinforcing over time.
      Experiences from a North-South collaborative effort provide some lessons in such
      partnership building: In Uganda and Denmark, respectively, the World Wildlife
      Fund and the network organization access2innovation have mobilized stakeholders
      around improving the municipal solid waste management system in Kasese District.
      Through a municipal solid waste management system characterization and mapping
      exercise, some emergent lessons and guiding principles in partnership building
      point to both pitfalls and opportunities for designing sustainable pathways.
      First, socio-technical lock-in effects in the municipal solid waste management
      system can stand in the way of partnerships based on introducing biogas or
      incineration technologies. However, opportunities in the municipal solid waste
      management system can exist within other areas, and synergies can be sought with
      interlinking systems, such as those represented with sanitation. 

PMID- 25378255
TI  - Hydrometallurgical process for the recovery of metal values from spent lithium
      ion batteries in citric acid media.
AB  - In this paper, a hydrometallurgical process has been proposed to recover valuable
      metals from spent lithium-ion batteries in citric acid media. Leaching
      efficiencies as high as 97%, 95%, 94%, and 99% of Ni, Co, Mn, and Li were
      achieved under the optimal leaching experimental conditions of citric acid
      concentration of 2 mol L(-1), leaching temperature of 80  degrees C, leaching
      time of 90 min, liquid-solid ratio of 30 ml g(-1), and 2 vol. % H2O2. For the
      metals recovery process, nickel and cobalt were selectively precipitated by
      dimethylglyoxime reagent and ammonium oxalate sequentially. Then manganese was
      extracted by Na-D2EHPA and the manganese-loaded D2EHPA was stripped with sulfuric
      acid. The manganese was recovered as MnSO4 in aqueous phase and D2EHPA could be
      reused after saponification. Finally, lithium was precipitated by 0.5 mol L(-1)
      sodium phosphate. Under their optimal conditions, the recovery percentages of Ni,
      Co, Mn, and Li can reach 98%, 97%, 98%, and 89%, respectively. This is a
      relatively simple route in which all metal values could be effectively leached
      and recovered in citric acid media. 

PMID- 25378256
TI  - Co-pyrolysis behaviour and kinetic of two typical solid wastes in China and
      characterisation of activated carbon prepared from pyrolytic char.
AB  - This is the first study on the co-pyrolysis of spent substrate of Pleurotus
      ostreatus and coal tar pitch, and the activated carbon prepared from the
      pyrolytic char. Thermogravimetry (TG) analysis was carried out taking spent
      substrate, coal tar pitch and spent substrate-coal tar pitch mixture. The
      activation energies of pyrolysis reactions were obtained via the Flynn-Wall-Ozawa
      and Kissinger-Akahira-Sunose methods. The kinetic models were determined by the
      master-plots method. The activated carbons were characterised by N2-adsorption,
      Fourier transform infrared spectroscopy and X-ray diffraction. Experimental
      results demonstrated a synergistic effect happened during co-pyrolysis, which was
      characterised by a decreased maximum decomposition rate and an enhanced char
      yield. The average activation energies of the pyrolysis reactions of spent
      substrate, coal tar pitch and the mixture were 115.94, 72.92 and 94.38 kJ mol(-1)
      for the Flynn-Wall-Ozawa method, and 112.17, 65.62 and 89.91 kJ mol(-1) for the
      Kissinger-Akahira-Sunose method. The reaction model functions were f(alpha) = (1
      alpha)(3.42), (1-alpha)(1.72) and (1-alpha)(3.07) for spent substrate, coal tar
      pitch and the mixture, respectively. The mixture char-derived activated carbon
      had a Brunauer-Emmett-Teller surface area up to 1337 m(2) g(-1) and a total pore
      volume of 0.680 cm(3) g(-1). Mixing spent substrate with coal tar pitch led to
      the creation of more micropores and a higher surface area compared with the
      single spent substrate and coal tar pitch char. Also, the mixture char-derived
      activated carbon had a higher proportion of aromatic stacking. This study
      provides a reference for the utilisation of spent substrate and coal tar pitch
      via co-pyrolysis, and their pyrolytic char as a promising precursor of activated
      carbon. 

PMID- 25378257
TI  - Construction technique of disposable bin from sludge cake and its environmental
      risk.
AB  - OBJECTIVES: Now, a lot of researchers have tried to make recycled rigid materials
      from the sludge cake produced in paper mill industries for the purpose of
      decreasing its volume. In this study, the researchers tried to make economically
      a disposable bin and to examine whether it is toxic or not to the outside
      environment. METHODS: To make a disposable bin, the researchers used the sludge
      cake, a plastic basket, as a fixed mold, white cloth or newspaper, as a removable
      supporter for wrapping around the mold, and latex or plaster, as a binder. The
      strength of the samples was measured by tensile-stress testing. The water
      absorption was evaluated by Cobb test. As toxicological tests, leaching test and
      seed germination test were selected. RESULTS: It was possible to form the
      disposal bin from the cleaned sludge cake. They seemed safe to carry garbage in
      the industry judging from the results of tensile-stress testing. Some of them
      showed less water absorptiveness (higher water resistance) in the results of Cobb
      test. The results of leaching test showed small values of three heavy metals,
      lead, nickel and copper, in the leachate. The seed germination test suggested no
      adverse effects of the bins in the clay and sand on the tomato growth.
      CONCLUSIONS: The results of these tests suggest that the bins have good strength,
      sufficient water resistance and no toxicological effect on the environment. This
      new recycled bin has the possibility to solve the environmental and health
      problems at disposing the sludge cake.

PMID- 25378258
TI  - Toxoplasma gondii infection among sheep and goats in Iran: a systematic review
      and meta-analysis.
AB  - Toxoplasmosis, a cosmopolitan parasitic infection caused by Toxoplasma gondii, is
      frequently found in meat-producing animals and human beings. This review and meta
      analysis study was performed to evaluate the overall prevalence of T. gondii
      infection among sheep and goats in Iran. Data were systematically collected from
      1977 to 2012 in Iran on the following electronic databases: PubMed, Google
      Scholar, Science Direct, Scopus, Web of Science, Magiran, Irandoc, IranMedex, and
      Scientific Information Database (SID). Additionally, abstracts of national
      scientific congresses and dissertations were included. A total of 34 articles in
      field of sheep and 18 articles about goat toxoplasmosis, totalizing to the
      examination of 14,372 sheep and 3,120 goats, reporting prevalence of
      toxoplasmosis from different regions of Iran fulfilled our eligibility criteria.
      The overall prevalence rate of toxoplasmosis in Iran was estimated to be 31% (95%
      confidence interval (CI) = 0.259825 to 0.352382) in sheep and 27% (95% CI =
      0.140097 to 0.424782) in goats, respectively. There was no significant difference
      in infection rate between males and females among sheep (odds ratio (OR) = 1.002,
      95% CI = 0.59 to 1.696) and goats (OR = 1.027, 95% CI = 0.685 to 1.541). Analysis
      revealed that infection rate in sheep over than 1 year old was 2.4 times more
      than that in less than 1 year old (OR = 2.396, 95% CI = 1.050 to 5.467). This
      systematic review and meta-analysis study revealed that infection is widespread
      in Iran. Further studies are required to improve strategies for controlling
      infection among flocks and consequently in human population.

PMID- 25378259
TI  - Removal of Anisakis simplex allergens from infected fish during the washing step
      of surimi production.
AB  - BACKGOUND: The washing operation of fish muscle is one of the key steps in the
      production of surimi. The aim of this study was to assess in parasitised minced
      fish the effect of the washing steps on the allergen removal of Anisakis simplex
      and on protein yield during surimi processing. Experimentally infected hake
      (Merluccius merluccius) (50 Anisakis simplex s.s L3 larvae per 100 g of muscle)
      underwent three successive washing steps with water, phosphate buffer (20 mmol L(
      1) ), sodium bicarbonate (60 mmol L(-1) ), or sodium hypochlorite (0.27 mmol L(
      1) ) in the surimi processing (4 kg muscle, 1:4 w/v for each solution). Total
      protein concentration and A. simplex antigens and allergens were evaluated in
      each waste fraction. RESULTS: The highest removal of Ani s 4 and A. simplex
      antigens was achieved by using phosphate buffer, together with a good protein
      yield in the raw surimi. Decrease of the concentration of allergens and antigens
      as a function of the washing steps rendered a linear trend (R(2) = 0.95 and 0.98
      for Ani s 4 and A. simplex antigens, respectively). CONCLUSION: The conditions
      for an optimal removal of Anisakis allergens can be established and calculated as
      a function of the washing steps. This approach opens a line to utilise
      parasitised fish in a safer way. (c) 2014 Society of Chemical Industry.

PMID- 25378260
TI  - An apocryphal case of craniopagus parasiticus: the legend of Edward Mordake.

PMID- 25378261
TI  - The collateral circulation in pediatric moyamoya disease.
AB  - PURPOSE: The descriptions of collateral circulation in moyamoya have so far been
      a mixture of topography-based and vessels' source-based analyses. We aimed to
      investigate the anatomy and systematize the vascular anastomotic networks in
      pediatric moyamoya disease. METHODS: From a series of 25 consecutive complete
      angiographic studies of newly diagnosed children with moyamoya, 14 children had
      moyamoya disease and 11 were diagnosed with moyamoya syndrome, i.e., moyamoya
      angiopathy with some additional concomitant systemic disease. We retrospectively
      analyzed the arterial branches supplying the moyamoya anastomotic networks, their
      origin, course, location, and connections with the recipient vessels. RESULTS: We
      describe four types of anastomotic networks in children with moyamoya disease,
      two superficial-meningeal and two deep-parenchymal. As superficial-meningeal, we
      defined the leptomeningeal and the durocortical networks. Apart from the
      previously described leptomeningeal network observed in the convexial watershed
      zones, we report on the basal temporo-orbitofrontal leptomeningeal network. The
      second superficial-meningeal network is the durocortical network, which can be
      basal or calvarian in location. We define as deep-parenchymal networks the
      nonpreviously described subependymal network and the inner striatal and inner
      thalamic networks. The subependymal network is fed by the intraventricular
      branches of the choroidal system and diencephalic perforators, which at the level
      of the periventricular subependymal zone, anastomose with medullary-cortical
      arteries as well as with striatal arteries. The inner striatal and thalamic
      networks are constituted by intrastriatal connections among striatal arteries and
      intrathalamic connections among thalamic arteries when the disease compromises
      the origin of one or more sources of their supply. CONCLUSION: The previously
      inexplicitly described "moyamoya abnormal network" in pediatric moyamoya disease
      can be described as a composition of four anastomotic networks with distinct
      angioarchitecture. A better understanding of the collateralization in moyamoya
      may help in defining a new staging system of the disease with clinical relevance.

PMID- 25378262
TI  - Hepatic artery stenosis after liver transplantation: is endovascular treatment
      always necessary?
AB  - Hepatic artery stenosis (HAS) is thought to predispose patients to biliary
      complications secondary to ischemic injury. Despite this, the clinical
      significance of HAS remains poorly defined. The aims of this study were to
      determine the prevalence and outcomes of HAS and to define which patients might
      benefit from endovascular treatment. From a prospective database of 662 adult
      patients undergoing liver transplantation between 2000 and 2011, we identified 54
      patients who developed HAS. HAS was defined as any stenosis > 70% that was seen
      during multidetector computed tomographic angiography (MDCTA) or digital
      subtraction angiography. The benefit of endovascular therapy was evaluated with
      propensity score matching. New biliary complications occurred in 17 patients
      (31.4%), and 23 of the 54 study patients with HAS received endovascular
      treatment. Among the propensity score-matched patients, the biliary stricture
      free survival time was significantly longer for those who received endovascular
      therapy (P = 0.03). An incidental diagnosis (P = 0.07) and a time from
      transplantation > 6 months (P = 0.021) were associated with a reduced risk of
      developing biliary stricture. Patients with symptomatic HAS who received
      treatment had better biliary stricture-free survival than patients who were
      treated conservatively, although no significant difference was recorded (P =
      0.11). No patient with asymptomatic HAS and normal liver function tests developed
      biliary strictures. In conclusion, HAS intervention was associated with improved
      biliary stricture-free survival. In patients with late-onset HAS (>=6 months) and
      asymptomatic patients, endovascular treatment is not warranted.

PMID- 25378264
TI  - Why women engage in anal intercourse: results from a qualitative study.
AB  - This study used qualitative methods to assess why women engage in heterosexual
      anal (receptive) intercourse (AI) with a male partner. Four focus groups which
      comprised women from diverse ethnicities were conducted. All groups were
      digitally recorded for transcription; transcripts were analyzed using the methods
      of grounded theory to determine themes. Women's reasons for engaging in anal
      intercourse with a male partner can be described in broad categories including
      that the women wanted to have anal intercourse, either because of their own
      desire, to please a male partner, or they were responding to a quid pro quo
      situation. The riskiness of AI was assessed within relationship contexts. Past
      experience with AI including emotional and physical reactions was identified.
      Among the negative physical experiences of AI were pain and disliking the
      sensation, and uncomfortable side effects, such as bleeding of the rectum.
      Negative emotional experiences of AI included feelings of shame, disgust, and
      being offended by something her male partner did, such as spitting on his penis
      for lubrication. Positive physical experiences included liking the sensation.
      Many of the women also endorsed positive emotional experiences of AI, including
      that it was more intimate than vaginal sex, and that it was something they
      reserved only for special partners. The majority of AI episodes were unplanned
      and not discussed prior to initiation. Pain during AI was mitigated by the use of
      lubricants or illicit drugs. Even those women who found pleasure in AI expressed
      a preference for vaginal intercourse. 

PMID- 25378265
TI  - Sexual Fluidity and Related Attitudes and Beliefs Among Young Adults with a Same
      Gender Orientation.
AB  - Little research has examined whether experiencing sexual fluidity--changes over
      time in attractions and sexual orientation identity--is related to specific
      cognitions. This study explored attitudes and beliefs among sexually fluid and
      non-sexually fluid individuals and developed two new measures of sexuality
      beliefs based on Diamond's sexual fluidity research and Dweck's psychological
      theory of intelligence beliefs. Participants were 188 female and male young
      adults in the United States with a same-gender orientation, ages 18-26 years.
      Participants completed an online questionnaire which assessed sexual fluidity in
      attractions and sexual orientation identity, attitudes toward bisexuality,
      sexuality beliefs, and demographics. Sexual fluidity in attractions was reported
      by 63 % of females and 50 % of males, with 48 % of those females and 34 % of
      those males reporting fluidity in sexual orientation identity. No significant
      gender differences in frequency of sexual fluidity were observed. Sexually fluid
      females had more positive attitudes toward bisexuality than non-sexually fluid
      females; however, no significant difference was observed for males. Females were
      more likely than males to endorse sexual fluidity beliefs and to believe that
      sexuality is changeable; and sexually fluid persons were more likely than non
      sexually fluid persons to hold those two beliefs. Among males, non-sexually fluid
      individuals were more likely than sexually fluid individuals to believe that
      sexuality is something an individual is born with. Females were more likely than
      males to endorse the belief that sexuality is influenced by the environment.
      Findings from this research link sexual fluidity with specific cognitions.

PMID- 25378263
TI  - Light-emitting diode therapy in exercise-trained mice increases muscle
      performance, cytochrome c oxidase activity, ATP and cell proliferation.
AB  - Light-emitting diode therapy (LEDT) applied over the leg, gluteus and lower-back
      muscles of mice using a LED cluster (630 nm and 850 nm, 80 mW/cm(2) , 7.2 J/cm(2)
      ) increased muscle performance (repetitive climbing of a ladder carrying a water
      filled tube attached to the tail), ATP and mitochondrial metabolism; oxidative
      stress and proliferative myocyte markers in mice subjected to acute and
      progressive strength training. Six bi-daily training sessions LEDT-After and LEDT
      Before-After regimens more than doubled muscle performance and increased ATP more
      than tenfold. The effectiveness of LEDT on improving muscle performance and
      recovery suggest applicability for high performance sports and in training
      programs. Positioning of the mice and light-emitting diode therapy (LEDT) applied
      on mouse legs, gluteus and lower-back muscles without contact. 

PMID- 25378268
TI  - An experimental and three-dimensional computational study on the aerodynamic
      contribution to the passive pitching motion of flapping wings in hovering flies.
AB  - The relative importance of the wing's inertial and aerodynamic forces is the key
      to revealing how the kinematical characteristics of the passive pitching motion
      of insect flapping wings are generated, which is still unclear irrespective of
      its importance in the design of insect-like micro air vehicles. Therefore, we
      investigate three species of flies in order to reveal this, using a novel fluid
      structure interaction analysis that consists of a dynamically scaled experiment
      and a three-dimensional finite element analysis. In the experiment, the dynamic
      similarity between the lumped torsional flexibility model as a first
      approximation of the dipteran wing and the actual insect is measured by the
      Reynolds number Re, the Strouhal number St, the mass ratio M, and the Cauchy
      number Ch. In the computation, the three-dimension is important in order to
      simulate the stable leading edge vortex and lift force in the present Re regime
      over 254. The drawback of the present experiment is the difficulty in satisfying
      the condition of M due to the limitation of available solid materials. The
      novelty of the present analysis is to complement this drawback using the
      computation. We analyze the following two cases: (a) The equilibrium between the
      wing's elastic and fluid forces is dynamically similar to that of the actual
      insect, while the wing's inertial force can be ignored. (b) All forces are
      dynamically similar to those of the actual insect. From the comparison between
      the results of cases (a) and (b), we evaluate the contributions of the
      equilibrium between the aerodynamic and the wing's elastic forces and the wing's
      inertial force to the passive pitching motion as 80-90% and 10-20%, respectively.
      It follows from these results that the dipteran passive pitching motion will be
      based on the equilibrium between the wing's elastic and aerodynamic forces, while
      it will be enhanced by the wing's inertial force. 

PMID- 25378267
TI  - Police on the front line of community geriatric health care: challenges and
      opportunities.
AB  - As the population ages, police increasingly serve as first responders to
      incidents involving older adults in which aging-related health plays a critical
      role. The goals of this study were to assess police officers' knowledge of aging
      related health, to identify challenges police experience in their encounters with
      older adults, and to describe their recommendations for how to address those
      challenges. This was a mixed-methods study of 141 San Francisco police officers
      recruited from mandatory police trainings between 2011 and 2013. Descriptive
      statistics were used to analyze 141 self-administered questionnaires, and
      principles of grounded theory were used to analyze open-ended questionnaire
      responses and 11 additional qualitative interviews. Eighty-nine percent of
      officers reported interacting with older adults at least monthly. Although 84% of
      police reported prior training in working with older adults, only 32% rated
      themselves as knowledgeable about aging-related health. Participants described
      themselves as first responders to medical and social emergencies involving older
      adults and identified several challenges, including identifying and responding to
      aging-related conditions and ensuring appropriate medical and social service
      handoffs. To address these challenges, officers recommended developing trainings
      focused on recognizing and responding to aging-related conditions and improving
      police knowledge of community resources for older adults. They also called for
      enhanced communication and collaboration between police and clinicians. These
      findings suggest that, because they assume a front-line role in responding to
      older adults with complex medical and social needs, many police may benefit from
      additional knowledge about aging-related health and community resources.
      Collaboration between police and healthcare providers presents an important
      opportunity to develop geriatrics training and interprofessional systems of care
      to support police work with a rapidly aging population. 

PMID- 25378269
TI  - A comparative study of monoclonal antibodies. 1. Phase behavior and protein
      protein interactions.
AB  - Protein phase behavior is involved in numerous aspects of downstream processing,
      either by design as in crystallization or precipitation processes, or as an
      undesired effect, such as aggregation. This work explores the phase behavior of
      eight monoclonal antibodies (mAbs) that exhibit liquid-liquid separation,
      aggregation, gelation, and crystallization. The phase behavior has been studied
      systematically as a function of a number of factors, including solution
      composition and pH, in order to explore the degree of variability among different
      antibodies. Comparisons of the locations of phase boundaries show consistent
      trends as a function of solution composition; however, changing the solution pH
      has different effects on each of the antibodies studied. Furthermore, the types
      of dense phases formed varied among the antibodies. Protein-protein interactions,
      as reflected by values of the osmotic second virial coefficient, are used to
      correlate the phase behavior. The primary findings are that values of the osmotic
      second virial coefficient are useful for correlating phase boundary locations,
      though there is appreciable variability among the antibodies in the apparent
      strengths of the intrinsic protein-protein attraction manifested. However, the
      osmotic second virial coefficient does not provide a clear basis to predict the
      type of dense phase likely to result under a given set of solution conditions.

PMID- 25378270
TI  - Determination of the polyphenolic content of a Capsicum annuum L. extract by
      liquid chromatography coupled to photodiode array and mass spectrometry detection
      and evaluation of its biological activity.
AB  - The present study was aimed to investigate the polyphenolic profile of a pepper
      (Capsicum annuum L.) extract from Algeria and evaluate its biological activity.
      The total polyphenol content of the extract was determined as 1.373 mg of gallic
      acid equivalents (+/-0.0046), whereas the flavonoids were determined as 0.098 mg
      of quercetin (+/-0.0015). The determination of the complete polyphenolic profile
      of the extract was achieved by liquid chromatography with an RP-amide column in
      combination with photodiode array and mass spectrometry detection through an
      electrospray ionization interface. A total of 18 compounds were identified, of
      which five were reported for the first time in the sample tested. Quercetin
      rhamnoside was the most abundant compound (82.6 MUg/g of fresh pepper) followed
      by quercetin glucoside (19.86 MUg/g). The antioxidant activity and antimicrobial
      effects were also determined. For the antimicrobial tests assessed against Gram
      positive and Gram-negative bacteria, kaempferol showed the strongest inhibitory
      effect followed by quercetin and caffeic acids. In the study of the cytotoxicity
      of the extract, the cancer cells (U937) were more affected than the normal cells
      (peripheral blood mononucleated cells), with more than 62% inhibition at the
      highest concentration. 

PMID- 25378271
TI  - Nanometer-Thick Single-Crystal Hexagonal Gd2 O3 on GaN for Advanced Complementary
      Metal-Oxide-Semiconductor Technology.
AB  - Hexagonal-phase single-crystal Gd2 O3 is deposited on GaN in a molecular beam
      epitaxy system. The dielectric constant is about twice that of its cubic
      counterpart when deposited on InGaAs or Si. The capacitive effective thickness of
      0.5 nm in hexagonal Gd2 O3 is perhaps the lowest on GaN-metal-oxide-semiconductor
      devices. The heterostructure is thermo dynamically stable at high temperatures
      and exhibits low interfacial densities of states after high-temperature
      annealing. 

PMID- 25378272
TI  - Sources of endocrine-disrupting compounds in North Carolina waterways: a
      geographic information systems approach.
AB  - The presence of endocrine-disrupting compounds (EDCs), particularly estrogenic
      compounds, in the environment has drawn public attention across the globe, yet a
      clear understanding of the extent and distribution of estrogenic EDCs in surface
      waters and their relationship to potential sources is lacking. The objective of
      the present study was to identify and examine the potential input of estrogenic
      EDC sources in North Carolina water bodies using a geographic information system
      (GIS) mapping and analysis approach. Existing data from state and federal
      agencies were used to create point and nonpoint source maps depicting the
      cumulative contribution of potential sources of estrogenic EDCs to North Carolina
      surface waters. Water was collected from 33 sites (12 associated with potential
      point sources, 12 associated with potential nonpoint sources, and 9 reference),
      to validate the predictive results of the GIS analysis. Estrogenicity (measured
      as 17beta-estradiol equivalence) ranged from 0.06 ng/L to 56.9 ng/L. However, the
      majority of sites (88%) had water 17beta-estradiol concentrations below 1 ng/L.
      Sites associated with point and nonpoint sources had significantly higher 17beta
      estradiol levels than reference sites. The results suggested that water 17beta
      estradiol was reflective of GIS predictions, confirming the relevance of
      landscape-level influences on water quality and validating the GIS approach to
      characterize such relationships.

PMID- 25378273
TI  - Acute exposure to ZnO nanoparticles induces autophagic immune cell death.
AB  - The increasing risk of incidental exposure to nanomaterials has led to mounting
      concerns regarding nanotoxicity. Zinc oxide nanoparticles (ZnO NPs) are produced
      in large quantities and have come under scrutiny due to their capacity to cause
      cytotoxicity in vitro and potential to cause harm in vivo. Recent evidence has
      indicated that ZnO NPs promote autophagy in cells; however, the signaling
      pathways and the role of ion release inducing toxicity remain unclear. In this
      study, we report that ZnO NPs are immunotoxic to primary and immortalized immune
      cells. Importantly, such immunotoxicity is observed in mice in vivo, since death
      of splenocytes is seen after intranasal exposure to ZnO NPs. We determined that
      ZnO NPs release free Zn(2+) that can be taken up by immune cells, resulting in
      cell death. Inhibiting free Zn(2+) ions in solution with EDTA or their uptake
      with CaCl2 abrogates ZnO NP-induced cell death. ZnO NP-mediated immune cell death
      was associated with increased levels of intracellular reactive oxygen species
      (ROS). ZnO NP death was not due to apoptosis, necroptosis or pyroptosis. Exposure
      of immune cells to ZnO NPs resulted in autophagic death and increased levels of
      LC3A, an essential component of autophagic vacuoles. Accordingly, ZnO NP-mediated
      upregulation of LC3A and induction of immune cell death were inhibited by
      blocking autophagy and ROS production. We conclude that release of Zn(2+) from
      ZnO NPs triggers the production of excessive intracellular ROS, resulting in
      autophagic death of immune cells. Our findings suggest that exposure to ZnO NPs
      has the potential to impact host immunity. 

PMID- 25378274
TI  - Pentalogy of Cantrell: the complete spectrum.

PMID- 25378275
TI  - Pyrogenic organic matter production from wildfires: a missing sink in the global
      carbon cycle.
AB  - Wildfires release substantial quantities of carbon (C) into the atmosphere but
      they also convert part of the burnt biomass into pyrogenic organic matter (PyOM).
      This is richer in C and, overall, more resistant to environmental degradation
      than the original biomass, and, therefore, PyOM production is an efficient
      mechanism for C sequestration. The magnitude of this C sink, however, remains
      poorly quantified, and current production estimates, which suggest that ~1-5% of
      the C affected by fire is converted to PyOM, are based on incomplete inventories.
      Here, we quantify, for the first time, the complete range of PyOM components
      found in-situ immediately after a typical boreal forest fire. We utilized an
      experimental high-intensity crown fire in a jack pine forest (Pinus banksiana)
      and carried out a detailed pre- and postfire inventory and quantification of all
      fuel components, and the PyOM (i.e., all visually charred, blackened materials)
      produced in each of them. Our results show that, overall, 27.6% of the C affected
      by fire was retained in PyOM (4.8 +/- 0.8 t C ha(-1)), rather than emitted to the
      atmosphere (12.6 +/- 4.5 t C ha(-1)). The conversion rates varied substantially
      between fuel components. For down wood and bark, over half of the C affected was
      converted to PyOM, whereas for forest floor it was only one quarter, and less
      than a tenth for needles. If the overall conversion rate found here were
      applicable to boreal wildfire in general, it would translate into a PyOM
      production of ~100 Tg C yr(-1) by wildfire in the global boreal regions, more
      than five times the amount estimated previously. Our findings suggest that PyOM
      production from boreal wildfires, and potentially also from other fire-prone
      ecosystems, may have been underestimated and that its quantitative importance as
      a C sink warrants its inclusion in the global C budget estimates.

PMID- 25378276
TI  - Functional morphology of the hallucal metatarsal with implications for inferring
      grasping ability in extinct primates.
AB  - Primate evolutionary morphologists have argued that selection for life in a fine
      branch niche resulted in grasping specializations that are reflected in the
      hallucal metatarsal (Mt1) morphology of extant "prosimians", while a transition
      to use of relatively larger, horizontal substrates explains the apparent loss of
      such characters in anthropoids. Accordingly, these morphological characters-Mt1
      torsion, peroneal process length and thickness, and physiological abduction angle
      have been used to reconstruct grasping ability and locomotor mode in the earliest
      fossil primates. Although these characters are prominently featured in debates on
      the origin and subsequent radiation of Primates, questions remain about their
      functional significance. This study examines the relationship between these
      morphological characters of the Mt1 and a novel metric of pedal grasping ability
      for a large number of extant taxa in a phylogenetic framework. Results indicate
      greater Mt1 torsion in taxa that engage in hallucal grasping and in those that
      utilize relatively small substrates more frequently. This study provides evidence
      that Carpolestes simpsoni has a torsion value more similar to grasping primates
      than to any scandentian. The results also show that taxa that habitually grasp
      vertical substrates are distinguished from other taxa in having relatively longer
      peroneal processes. Furthermore, a longer peroneal process is also correlated
      with calcaneal elongation, a metric previously found to reflect leaping
      proclivity. A more refined understanding of the functional associations between
      Mt1 morphology and behavior in extant primates enhances the potential for using
      these morphological characters to comprehend primate (locomotor) evolution.

PMID- 25378277
TI  - Design and evaluation of endosomolytic biocompatible peptides as carriers for
      siRNA delivery.
AB  - Gene therapy using RNA interference (RNAi) technology has been explored to treat
      cancers, by regulating the expression of oncogene. However, even though small
      interfering RNA (siRNA), which triggers RNAi, may have great therapeutic
      potential, efforts at using them in vivo have been hampered by the difficulty of
      effective and safe delivery into cells of interest. In this study, to develop a
      safe and efficient carrier for in vitro and in vivo siRNA delivery, we designed a
      peptide library. These peptides are improved variants of a known peptide based
      siRNA carrier C6. All the modifications improved the transfection efficiency of
      C6 to some degree. After completing prescreening for activity, several promising
      candidates were used for further evaluation. Selected peptides C6M3 and C6M6
      could form stable complexes with siRNA. These complexes could be greatly uptaken
      by cells and showed a punctate perinuclear distribution. Moreover, peptide/siRNA
      complexes achieved high transfection efficiency in vitro without inducing
      substantial cytotoxicity. We have validated the therapeutic potential of this
      strategy for cancer treatment by targeting Bcl-2 gene in mouse tumor models, and
      demonstrated that tumor growth was inhibited. In order to address possible immune
      side effects of these peptide carriers, biocompatibility study in terms of
      complement activation and cytokine activation assay were carried out, whereas
      none of the peptides induced such effects. In conclusion, these results support
      the potential of these peptides as therapeutic siRNA carrier. 

PMID- 25378278
TI  - The syn/anti-dichotomy in the palladium-catalyzed addition of nucleophiles to
      alkenes.
AB  - In this review the stereochemistry of palladium-catalyzed addition of
      nucleophiles to alkenes is discussed, and examples of these reactions in organic
      synthesis are given. Most of the reactions discussed involve oxygen and nitrogen
      nucleophiles; the Wacker oxidation of ethylene has been reviewed in detail. An
      anti-hydroxypalladation in the Wacker oxidation has strong support from both
      experimental and computational studies. From the reviewed material it is clear
      that anti-addition of oxygen and nitrogen nucleophiles is strongly favored in
      intermolecular addition to olefin-palladium complexes even if the nucleophile is
      coordinated to the metal. On the other hand, syn-addition is common in the case
      of intramolecular oxy- and amidopalladation as a result of the initial
      coordination of the internal nucleophile to the metal. 

PMID- 25378279
TI  - Ring reconstruction on a trichalcogenasumanene buckybowl: a facile approach to
      donor-acceptor-type [5-6-7] fused planar polyheterocycles.
AB  - The transformation of trichalcogenasumanene buckybowls into donor-acceptor-type
      [5-6-7] fused polyheterocycles is disclosed. The strategy involves a highly
      efficient ring-opening of the flanking benzene upon oxidation at room
      temperature, and facile ring closure by functional-group transformation.
      Crystallographic studies indicate that the resulting [5-6-7] fused
      polyheterocycles possess a planar conformation owing to the release of ring
      strain by expansion of one of the six-membered flanking rings to the seven
      membered one. Additionally, the [5-6-7] fused polyheterocycles bear electron
      withdrawing groups, which reduce the HOMO-LUMO energy gap, and display broad
      absorption bands extending to lambda=590 nm. Consequently, these compounds show
      strong red emission with fluorescence quantum yields of up to 38 %. 

PMID- 25378280
TI  - Development and validation of UHPLC-MS/MS assay for rapid determination of a
      carvone Schiff base of isoniazid (CSB-INH) in rat plasma: application to
      pharmacokinetic study.
AB  - In this study, a fast UHPLC-MS/MS method was developed and validated for the
      determination of a novel potent carvone Schiff base of isoniazid (CSB-INH) in rat
      plasma using carbamazepine as an internal standard (IS). After a single-step
      protein precipitation by acetonitrile, CSB-INH and IS were separated on an
      Acquity BEH(TM) C18 column (50 * 2.1 mm, 1.7 um) under an isocratic mobile phase,
      consisting of acetonitrile: 10 mM ammonium acetate (95:5, v/v), at a flow rate of
      0.3 mL/min. Quantification was performed on a triple quadrupole tandem mass
      spectrometer in multiple reactions monitoring mode by using positive electrospray
      ionization source. The precursor to product ion transitions were set at m/z
      270.08 -> 79.93 for CSB-INH and m/z 237.00 -> 178.97 for IS. The proposed method
      was validated in compliance with US Food and Drug Administration and European
      Medicines Agency guidelines for bioanalytical method validation. The method was
      found to be linear in the range of 0.35-2500 ng/mL (r(2)  >= 0.997) with a lower
      limit of quantification of 0.35 ng/mL. The intra- and inter-day precision values
      were <=12.0% whereas accuracy values ranged from 92.3 to 108.7%. In addition,
      other validation results were within the acceptance criteria and the method was
      successfully applied in a pharmacokinetic study of CSB-INH in rats.

PMID- 25378281
TI  - Controlled porosity solubility modulated osmotic pump tablets of gliclazide.
AB  - A system that can deliver drug at a controlled rate is very important for the
      treatment of various chronic diseases such as diabetes, asthma, and heart
      disease. Poorly water-soluble drug with pH-dependent solubility such as
      gliclazide (GLZ) offers challenges in the controlled-release formulation because
      of low dissolution rate and poor bioavailability. Solid dispersion (SD) of GLZ
      consisted of hydroxypropyl cellulose (HPC-SSL) as a polymeric solubilizer was
      manufactured by hot melt extrusion (HME) technology. Then, controlled porosity
      osmotic pump (CPOP) tablet of gliclazide was designed to deliver drug in a
      controlled manner up to 16 h. The developed formulation was optimized for type
      and level of pore former and coating weight gain. The optimized formulation was
      found to exhibit zero order kinetics independent of pH and agitation speed but
      depends on osmotic pressure of dissolution media indicated that mechanism of drug
      release was osmotic pressure. The in vivo performance prediction of developed
      formulation using convolution approach revealed that the developed formulation
      was superior to the existing marketed extended-release formulation in terms of
      attaining steady state plasma levels and indicated adequate exposure in
      translating hypoglycemic response. The prototype solubilization method combined
      with controlled porosity osmotic pump based technique could provide a unique way
      to increase dissolution rate and bioavailability of many poorly water-soluble,
      narrow therapeutic index drugs used in diabetes, cardiovascular diseases, etc. 

PMID- 25378282
TI  - Increases in lifestyle activities as a result of experience Corps(r)
      participation.
AB  - Experience Corps(r) (EC) was designed to simultaneously increase cognitive,
      social, and physical activity through high-intensity volunteerism in elementary
      school classrooms. It is, therefore, highly likely that EC participation may
      alter pre-existing patterns of lifestyle activity. This study examined the impact
      of "real-world" volunteer engagement on the frequency of participation in various
      lifestyle activities over a 2-year period. Specifically, we examined intervention
      related changes on reported activity levels at 12 and 24 months post-baseline
      using Intention-to-Treat (ITT) and Complier Average Causal Effect (CACE)
      analyses, which account for the amount of program exposure. ITT analyses
      indicated that, compared to the control group, EC participants reported modest
      increases (approximately half a day/month) in overall activity level, especially
      in intellectual and physical activities 12 months post-baseline. Increases in
      activity were not found at the 24-month assessment. CACE models revealed similar
      findings for overall activity as well as for intellectual and physical activities
      at 12 months. Additionally, CACE findings suggested modest increases in social
      activity at 12 months and in intellectual and passive activities at 24 months
      post-baseline. This community-based, health promotion intervention has the
      potential to impact lifestyle activity, which may lead to long-term increases in
      activity and to other positive cognitive, physical, and psychosocial health
      outcomes. 

PMID- 25378283
TI  - Telling stories about medicines safety.

PMID- 25378284
TI  - Epidermal barrier disorders and corneodesmosome defects.
AB  - Corneodesmosomes are modified desmosomes present in the stratum corneum (SC).
      They are crucial for SC cohesion and, thus, constitute one of the pivotal
      elements of the functional protective barrier of human skin. Expression of
      corneodesmosomes and, notably, the process of their degradation are probably
      altered during several dermatoses leading to the disruption of the permeability
      barrier or to abnormal, often compensative, SC accumulation. These different
      situations are reviewed in the present paper. 

PMID- 25378285
TI  - Differences in hormone localisation patterns of K and L type enteroendocrine
      cells in the mouse and pig small intestine and colon.
AB  - This study has investigated the patterns of colocalisation of the conventional K
      cell marker, glucagon-like insulinotropic peptide (GIP), and the L cell markers,
      glucagon like peptide-1 (GLP-1) and peptide YY (PYY), in enteroendocrine cells
      (EEC) of the small intestine and colon of mouse and pig. All combinations of the
      hormones, 3 in a cell, 2 in a cell and 1 at a time, were encountered. In both
      species, the three most common EEC types contained (1) both GLP-1 and PYY but not
      GIP, (2) GLP-1 alone or (3) GIP plus GLP-1 without PYY. Few GIP plus PYY cells
      and rare cells containing all 3 hormones were encountered. Gradients of cell
      types occurred along the intestine. For example, in mouse, there were no PYY
      cells in the duodenum and few in the jejunum, but >50% of labelled EEC in the
      distal ileum and colon were PYY immunoreactive. By contrast, over 40% of EEC in
      the pig duodenum contained PYY, and most also contained either GLP-1 or GIP. The
      gradient in pig was less pronounced. It is concluded that the traditional
      classification of K and L cells requires revision, and that there are major inter
      species differences in the patterns of colocalisation of hormones that have been
      used to characterise K and L cells.

PMID- 25378286
TI  - Doctors in Moscow rally against planned hospital closures.

PMID- 25378287
TI  - Quality changes during cod (Gadus morhua) desalting at different temperatures.
AB  - BACKGROUND: To advise consumers and manufacturers regarding decreasing the time
      needed to desalt salted cod (a time-consuming process), there is a need to
      develop knowledge about quality changes at different desalting temperatures. The
      objective of this work was to evaluate the physico-chemical, microbiological and
      sensory quality changes and their causes during cod desalting at 5, 10 and 15 
      degrees C, using a cod/water ratio of 1:9 without water changes. The influence of
      slices with different thickness and different desalting times was also evaluated.
      RESULTS: Desalting promoted a decrease in the levels of total volatile basic
      nitrogen, thiobarbituric acid reactive substances and free amino acids nitrogen
      (FAA-N). The highest FAA-N values were found in 'thicker' samples desalted at 15 
      degrees C due to the higher proteolytic bacteria number observed in these
      samples, which activity compensated the leaching of soluble components to the
      desalting solution. The water uptake and the salt leaching out of the muscle
      found during the processes created conditions for the bacterial growth,
      contributing to the spoilage at 15  degrees C. Based on fresh odour and 'off'
      flavours results, 'thicker' samples desalted at 15  degrees C after 72 h were
      close to spoilage and on microbial levels were spoiled. CONCLUSION: In order to
      extend the shelf life and safety of cod desalted products, desalting at
      temperatures above 10  degrees C is not advisable. (c) 2014 Society of Chemical
      Industry.

PMID- 25378289
TI  - Synthesis of cellulose methylcarbonate in ionic liquids using dimethylcarbonate.
AB  - Dialkylcarbonates are viewed as low-cost, low-toxicity reagents, finding
      application in many areas of green chemistry. Homogeneous alkoxycarbonylation of
      cellulose was accomplished by applying dialkycarbonates (dimethyl and diethyl
      carbonate) in the ionic liquid-electrolyte trioctylphosphonium acetate ([P8881
      ][OAc])/DMSO or 1-ethyl-3-methylimidazolium acetate ([emim][OAc]). Cellulose
      dialkylcarbonates with a moderate degree of substitution (DS~1) are accessible
      via this procedure and cellulose methylcarbonate was thoroughly characterized for
      its chemical and physical properties after regeneration. This included HSQC &
      HMBC NMR, ATR-IR, molecular weight distribution, morphology, thermal properties,
      and barrier properties after film formation. 

PMID- 25378290
TI  - The National Longitudinal Study of Adolescent to Adult Health (Add Health)
      sibling pairs genome-wide data.
AB  - Here we provide a detailed description of the genome-wide information available
      on the National Longitudinal Study of Adolescent to Adult Health (Add Health)
      sibling pair subsample (Harris et al. in Twin Res Hum Genet 16:391-398, 2013). A
      total of 2,020 samples were genotyped (including duplicates) arising from 1946
      Add Health individuals from the sibling pairs subsample. After various steps for
      quality control (QC) and quality assurance (QA), we have high quality genome-wide
      data available on 1,888 individuals. In this report, we first highlight the QC
      and QA steps that were taken to prune the data of poorly performing samples and
      genetic markers. We further estimate the pairwise biological relationships using
      genome-wide data and compare those estimates to the assumed relationships in Add
      Health. Additionally, using genome-wide data from known regional reference
      populations from Europe, West Africa, North and South America, Japan and China,
      we estimate the relative genetic ancestry of the respondents. Finally, rather
      than conducting a traditional cross-sectional genome-wide association study
      (GWAS) of body mass index (BMI), we opted to utilize the extensive publicly
      available genome-wide information to conduct a weighted GWAS of longitudinal BMI
      while accounting for both family and ethnic variation. 

PMID- 25378291
TI  - National survey of adult transplant hepatologists on the pediatric-to-adult care
      transition after liver transplantation.
AB  - Adult transplant hepatologists face challenges in providing care to young adults
      who received liver transplants during childhood. Because prior studies have
      focused mainly on pediatric providers, understanding these issues from the
      perspective of the adult hepatologist may provide novel insights and identify key
      barriers to care in this population. We conducted a national survey of adult
      transplant hepatologists to assess factors that may affect the transition of
      recipients from pediatric care to adult care. More than half of transplant
      hepatologists from all United Network for Organ Sharing regions (236/408 or
      57.8%) completed the survey, and they reported that only 46.1% of patients
      arrived at their first adult clinic with both adequate knowledge of their
      condition and a parent/guardian. Moreover, 32.4% reported having no transition
      strategy, and only 15.5% reported having a formal transition program. The
      respondents reported that the greatest barriers to optimal care were patients'
      poor adherence and their limited knowledge and management of their condition.
      Those who reported participating in a formal transition program were less likely
      to report an inability of patients to discuss the impact of their condition on
      their overall daily life, fitness, and sexuality as a barrier to transition (odds
      ratio = 0.40, 95% confidence interval = 0.16-1.00). Our survey suggests that a
      formalized transition process is uncommon in adult transplant hepatology clinics
      and that improving patient knowledge, understanding specific components of
      effective transition programs, and incorporating input from adult providers in
      designing such programs may improve this process.

PMID- 25378292
TI  - Roles of interstitial fraction and load conditions on the dynamic binding
      capacity of proteins on capillary-channeled polymer fiber columns.
AB  - Capillary-channeled polymer (C-CP) fibers are used as a stationary phase for ion
      exchange chromatography of proteins. Collinear packing of the fibers permits
      operation at high linear velocities (Uo  > 100 mm s(-1)) and low backpressure
      (<2,000 psi) on analytical-scale columns. Rapid solvent transport is matched with
      very efficient solute mass transfer as fibers are virtually non-porous with
      respect to the size of the target protein molecules. Lack of porosity of course
      limits the equilibrium binding capacity of stationary phases. Breakthrough curves
      and frontal analysis are used to better understand trade-offs between the kinetic
      and thermodynamic properties as C-CP fibers are applied in preparative
      situations. Fiber columns packed to different interstitial fraction values affect
      both the total fiber surface area (e.g., equilibrium binding capacity [EBC]) and
      the permittivity to flow and mass transport characteristics (e.g., dynamic
      binding capacity [DBC]). The EBC of the nylon 6 C-CP fibers was found to be 1.30
      mg g(-1), with isotherms that were best matched by a Moreau model, showing
      linearity up to solute concentrations of ~0.4 mg mL(-1). Isotherms generated
      under flow conditions were equally well approximated using Langmuir, Freundlich,
      and Moreau isotherm models. Fairly linear responses were seen up to the maximum
      load concentration of 1.2 mg mL(-1). Counterintuitively, dynamic studies revealed
      that conditions of high column porosity yielded a DBC that is ~70% higher than
      the EBC. These findings point to potential advantages in terms downstream
      processing applications, where protein throughput and yield are critical metrics.

PMID- 25378293
TI  - The kinematics of the California sea lion foreflipper during forward swimming.
AB  - To determine the two-dimensional kinematics of the California sea lion
      foreflipper during thrust generation, a digital, high-definition video is
      obtained using a non-research female sea lion at the Smithsonian National
      Zoological Park in Washington, DC. The observational videos are used to extract
      maneuvers of interest--forward acceleration from rest using the foreflippers and
      banked turns. Single camera videos are analyzed to digitize the flipper during
      the motions using 10 points spanning root to tip in each frame. Digitized shapes
      were then fitted with an empirical function that quantitatively allows for both
      comparison between different claps, and for extracting kinematic data. The
      resulting function shows a high degree of curvature (with a camber of up to 32%).
      Analysis of sea lion acceleration from rest shows thrust production in the range
      of 150-680 N and maximum flipper angular velocity (for rotation about the
      shoulder joint) as high as 20 rad s-1. Analysis of turning maneuvers indicate
      extreme agility and precision of movement driven by the foreflipper surfaces.

PMID- 25378294
TI  - No observable effect of a glyphosate-based herbicide on two top predators of
      temporal water bodies.
AB  - It has been implied that the application of pesticides is involved in the world
      wide decline of biodiversity, but little is known about the influence of these
      chemicals on key predators of temporary wetlands. The direct impacts were
      examined of a frequently applied glyphosate-based herbicide on larval Aeshna
      cyanea (Muller, 1764; Odonata, Insecta) and adult male Lissotriton vulgaris
      (Linnaeus, 1758; Caudata, Amphibia), 2 top predators of Central European
      ephemeral ponds. The effects of herbicide exposure were measured on survival,
      behavior, body mass change, and predatory activity in an outdoor mesocosm
      experiment lasting for 17 d. No significant effects of exposure were observed in
      either predator species. The results suggest that the herbicide has no immediate
      effect on the predators studied at environmentally relevant concentrations and
      that these predators can also fulfill their top-down regulatory role in
      contaminated ecosystems.

PMID- 25378295
TI  - Ligand-controlled regiodivergent nickel-catalyzed annulation of pyridones.
AB  - The 1,6-annulated 2-pyridone motif is found in many biologically active compounds
      and its close relation to the indolizidine and quinolizidine alkaloid core makes
      it an attractive building block. A nickel-catalyzed C-H functionalization of 2
      pyridones and subsequent cyclization affords 1,6-annulated 2-pyridones by
      selective intramolecular olefin hydroarylation. The switch between the exo- and
      endo-cyclization modes is controlled by two complementary sets of ligands.
      Irrespective of the ring size, the regioselectivity during the cyclization is
      under full catalyst control. Simple cyclooctadiene promotes an exo-selective
      cyclization, whereas a bulky N-heterocyclic carbene ligand results in an endo
      selective mode. The method was further applied in the synthesis of the lupin
      alkaloid cytisine.

PMID- 25378296
TI  - Angelina Jolie and medical decision science.

PMID- 25378297
TI  - Doctors and numbers: an assessment of the critical risk interpretation test.
AB  - BACKGROUND: Risk interpretation affects decision making. Yet, there is no valid
      assessment of how clinicians interpret the risk data that they commonly
      encounter. OBJECTIVE: To establish the reliability and validity of a 20-item test
      of clinicians' risk interpretation. METHODS: The Critical Risk Interpretation
      Test (CRIT) measures clinicians' abilities to 1) modify the interpretation based
      on meaningful differences in the outcome (e.g., disease specific v. all-cause
      mortality) and time period (e.g., lifetime v. 10-year mortality), 2) maintain a
      stable interpretation for different risk framings (e.g., relative v. absolute
      risk), and 3) correctly interpret how diagnostic testing modifies risk. There
      were 658 clinicians and medical trainees who participated: 116 nurse
      practitioners (NPs) at a national conference, 273 medical students at 1
      institution, 148 residents in internal medicine at 2 institutions, and 121
      internists at 1 institution. Participants completed a self-administered paper
      test during educational conferences. Seventeen evidence-based medicine experts
      took the test online and formally assessed content validity. Eighteen second-year
      medical students were recruited to take the test and a retest 3 weeks later to
      explore test-retest correlation. RESULTS: Expert review supported test clarity
      and content validity. Factor analysis supported that the CRIT identifies at least
      3 separable areas of clinician knowledge. Test-retest correlation was fair
      (intraclass correlation coefficient = 0.65; standard error = 0.15). Scores on our
      test correlated with other tests of related abilities. Mean test scores varied
      among groups, with differences in prior evidence-based medicine training and
      experience (93 for NPs, 101 for medical students, 101 for residents, 103 for
      academic internists, and 110 for physician experts; P < 0.001). CONCLUSIONS: Our
      results provide supporting evidence for the reliability and validity of the CRIT
      as an index of critical risk interpretation abilities, which is acceptable and
      feasible to administer in an educational setting.

PMID- 25378298
TI  - Touch at a distance sensing: lateral-line inspired MEMS flow sensors.
AB  - Evolution bestowed the blind cavefish with a resourcefully designed lateral-line
      of sensors that play an essential role in many important tasks including object
      detection and avoidance, energy-efficient maneuvering, rheotaxis etc. Biologists
      identified the two types of vital sensors on the fish bodies called the
      superficial neuromasts and the canal neuromasts that are responsible for flow
      sensing and pressure-gradient sensing, respectively. In this work, we present the
      design, fabrication and experimental characterization of biomimetic polymer
      artificial superficial neuromast micro-sensor arrays. These biomimetic micro
      sensors demonstrated a high sensitivity of 0.9 mV/(m s(-1)) and 0.022 V/(m s(-1))
      and threshold velocity detection limits of 0.1 m s(-1) and 0.015 m s(-1) in
      determining air and water flows respectively. Experimental results demonstrate
      that the biological canal inspired polymer encapsulation on the array of
      artificial superficial neuromast sensors is capable of filtering steady-state
      flows that could otherwise significantly mask the relevant oscillatory flow
      signals of high importance. 

PMID- 25378299
TI  - Personalizing, not patronizing: the case for patient autonomy by unbiased
      presentation of management options in stage I testicular cancer.
AB  - Testicular cancer (TC) is the most common neoplasm in males aged 15-40 years. The
      majority of patients have no evidence of metastases at diagnosis and thus have
      clinical stage I (CSI) disease [Oldenburg J, Fossa SD, Nuver J et al. Testicular
      seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi125-vi132; de Wit R,
      Fizazi K. Controversies in the management of clinical stage I testis cancer. J
      Clin Oncol 2006; 24: 5482-5492.]. Management of CSI TC is controversial and
      options include surveillance and active treatment. Different forms of adjuvant
      therapy exist, including either one or two cycles of carboplatin chemotherapy or
      radiotherapy for seminoma and either one or two cycles of cisplatin-based
      chemotherapy or retroperitoneal lymph node dissection for non-seminoma. Long-term
      disease-specific survival is ~99% with any of these approaches, including
      surveillance. While surveillance allows most patients to avoid additional
      treatment, adjuvant therapy markedly lowers the relapse rate. Weighing the net
      benefits of surveillance against those of adjuvant treatment depends on
      prioritizing competing aims such as avoiding unnecessary treatment, avoiding more
      burdensome treatment with salvage chemotherapy and minimizing the anxiety, stress
      and life disruption associated with relapse. Unbiased information about the
      advantages and disadvantages of surveillance and adjuvant treatment is a
      prerequisite for informed consent by the patient. In a clinical scenario like CSI
      TC, where different disease-management options produce indistinguishable long
      term survival rates, patient values, priorities and preferences should be taken
      into account. In this review, we provide an overview about risk factors for
      relapse, potential benefits and harms of adjuvant chemotherapy and active
      surveillance and a rationale for involving patients in individualized decision
      making about their treatment rather than adopting a uniform recommendation for
      all. 

PMID- 25378300
TI  - Opposing roles of mitochondrial and nuclear PARP1 in the regulation of
      mitochondrial and nuclear DNA integrity: implications for the regulation of
      mitochondrial function.
AB  - The positive role of PARP1 in regulation of various nuclear DNA transactions is
      well established. Although a mitochondrial localization of PARP1 has been
      suggested, its role in the maintenance of the mitochondrial DNA is currently
      unknown. Here we investigated the role of PARP1 in the repair of the
      mitochondrial DNA in the baseline and oxidative stress conditions. We used wild
      type A549 cells or cells depleted of PARP1. Our data show that intra
      mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision
      repair (BER) enzymes, namely EXOG and DNA polymerase gamma (Polgamma), which
      under oxidative stress become poly(ADP-ribose)lated (PARylated). Interaction
      between mitochondrial BER enzymes was significantly affected in the presence of
      PARP1. Moreover, the repair of the oxidative-induced damage to the mitochondrial
      DNA in PARP1-depleted cells was found to be more robust compared to control
      counterpart. In addition, mitochondrial biogenesis was enhanced in PARP1-depleted
      cells, including mitochondrial DNA copy number and mitochondrial membrane
      potential. This observation was further confirmed by analysis of lung tissue
      isolated from WT and PARP1 KO mice. In summary, we conclude that mitochondrial
      PARP1, in opposite to nuclear PARP1, exerts a negative effect on several
      mitochondrial-specific transactions including the repair of the mitochondrial
      DNA.

PMID- 25378301
TI  - miRDB: an online resource for microRNA target prediction and functional
      annotations.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that are extensively involved in
      many physiological and disease processes. One major challenge in miRNA studies is
      the identification of genes regulated by miRNAs. To this end, we have developed
      an online resource, miRDB (http://mirdb.org), for miRNA target prediction and
      functional annotations. Here, we describe recently updated features of miRDB,
      including 2.1 million predicted gene targets regulated by 6709 miRNAs. In
      addition to presenting precompiled prediction data, a new feature is the web
      server interface that allows submission of user-provided sequences for miRNA
      target prediction. In this way, users have the flexibility to study any custom
      miRNAs or target genes of interest. Another major update of miRDB is related to
      functional miRNA annotations. Although thousands of miRNAs have been identified,
      many of the reported miRNAs are not likely to play active functional roles or may
      even have been falsely identified as miRNAs from high-throughput studies. To
      address this issue, we have performed combined computational analyses and
      literature mining, and identified 568 and 452 functional miRNAs in humans and
      mice, respectively. These miRNAs, as well as associated functional annotations,
      are presented in the FuncMir Collection in miRDB. 

PMID- 25378302
TI  - Islander: a database of precisely mapped genomic islands in tRNA and tmRNA genes.
AB  - Genomic islands are mobile DNAs that are major agents of bacterial and archaeal
      evolution. Integration into prokaryotic chromosomes usually occurs site
      specifically at tRNA or tmRNA gene (together, tDNA) targets, catalyzed by
      tyrosine integrases. This splits the target gene, yet sequences within the island
      restore the disrupted gene; the regenerated target and its displaced fragment
      precisely mark the endpoints of the island. We applied this principle to search
      for islands in genomic DNA sequences. Our algorithm identifies tDNAs, finds
      fragments of those tDNAs in the same replicon and removes unlikely candidate
      islands through a series of filters. A search for islands in 2168 whole
      prokaryotic genomes produced 3919 candidates. The website Islander (recently
      moved to http://bioinformatics.sandia.gov/islander/) presents these precisely
      mapped candidate islands, the gene content and the island sequence. The algorithm
      further insists that each island encode an integrase, and attachment site
      sequence identity is carefully noted; therefore, the database also serves in the
      study of integrase site-specificity and its evolution. 

PMID- 25378303
TI  - iBeetle-Base: a database for RNAi phenotypes in the red flour beetle Tribolium
      castaneum.
AB  - The iBeetle-Base (http://ibeetle-base.uni-goettingen.de) makes available
      annotations of RNAi phenotypes, which were gathered in a large scale RNAi screen
      in the red flour beetle Tribolium castaneum (iBeetle screen). In addition, it
      provides access to sequence information and links for all Tribolium castaneum
      genes. The iBeetle-Base contains the annotations of phenotypes of several
      thousands of genes knocked down during embryonic and metamorphic epidermis and
      muscle development in addition to phenotypes linked to oogenesis and stink gland
      biology. The phenotypes are described according to the EQM (entity, quality,
      modifier) system using controlled vocabularies and the Tribolium morphological
      ontology (TrOn). Furthermore, images linked to the respective annotations are
      provided. The data are searchable either for specific phenotypes using a complex
      'search for morphological defects' or a 'quick search' for gene names and IDs.
      The red flour beetle Tribolium castaneum has become an important model system for
      insect functional genetics and is a representative of the most species rich
      taxon, the Coleoptera, which comprise several devastating pests. It is used for
      studying insect typical development, the evolution of development and for
      research on metabolism and pest control. Besides Drosophila, Tribolium is the
      first insect model organism where large scale unbiased screens have been
      performed. 

PMID- 25378304
TI  - RNA-dependent chromatin localization of KDM4D lysine demethylase promotes H3K9me3
      demethylation.
AB  - The JmjC-containing lysine demethylase, KDM4D, demethylates di-and tri
      methylation of histone H3 on lysine 9 (H3K9me3). How KDM4D is recruited to
      chromatin and recognizes its histone substrates remains unknown. Here, we show
      that KDM4D binds RNA independently of its demethylase activity. We mapped two non
      canonical RNA binding domains: the first is within the N-terminal spanning amino
      acids 115 to 236, and the second is within the C-terminal spanning amino acids
      348 to 523 of KDM4D. We also demonstrate that RNA interactions with KDM4D N
      terminal region are critical for its association with chromatin and subsequently
      for demethylating H3K9me3 in cells. This study implicates, for the first time,
      RNA molecules in regulating the levels of H3K9 methylation by affecting KDM4D
      association with chromatin.

PMID- 25378305
TI  - Revealing the amino acid composition of proteins within an expanded genetic code.
AB  - The genetic code can be manipulated to reassign codons for the incorporation of
      non-standard amino acids (NSAA). Deletion of release factor 1 in Escherichia coli
      enhances translation of UAG (Stop) codons, yet may also extended protein
      synthesis at natural UAG terminated messenger RNAs. The fidelity of protein
      synthesis at reassigned UAG codons and the purity of the NSAA containing proteins
      produced require careful examination. Proteomics would be an ideal tool for these
      tasks, but conventional proteomic analyses cannot readily identify the extended
      proteins and accurately discover multiple amino acid (AA) insertions at a single
      UAG. To address these challenges, we created a new proteomic workflow that
      enabled the detection of UAG readthrough in native proteins in E. coli strains in
      which UAG was reassigned to encode phosphoserine. The method also enabled
      quantitation of NSAA and natural AA incorporation at UAG in a recombinant
      reporter protein. As a proof-of-principle, we measured the fidelity and purity of
      the phosphoserine orthogonal translation system (OTS) and used this information
      to improve its performance. Our results show a surprising diversity of natural
      AAs at reassigned stop codons. Our method can be used to improve OTSs and to
      quantify amino acid purity at reassigned codons in organisms with expanded
      genetic codes. 

PMID- 25378306
TI  - Plastid-LCGbase: a collection of evolutionarily conserved plastid-associated gene
      pairs.
AB  - Plastids carry their own genetic material that encodes a variable set of genes
      that are limited in number but functionally important. Aside from orthology, the
      lineage-specific order and orientation of these genes are also relevant. Here, we
      develop a database, Plastid-LCGbase (http://lcgbase.big.ac.cn/plastid-LCGbase/),
      which focuses on organizational variability of plastid genes and genomes from
      diverse taxonomic groups. The current Plastid-LCGbase contains information from
      470 plastid genomes and exhibits several unique features. First, through a genome
      overview page generated from OrganellarGenomeDRAW, it displays general
      arrangement of all plastid genes (circular or linear). Second, it shows patterns
      and modes of all paired plastid genes and their physical distances across user
      defined lineages, which are facilitated by a step-wise stratification of
      taxonomic groups. Third, it divides the paired genes into three categories (co
      directionally-paired genes or CDPGs, convergently-paired genes or CPGs and
      divergently-paired genes or DPGs) and three patterns (separation, overlap and
      inclusion) and provides basic statistics for each species. Fourth, the gene
      pairing scheme is expandable, where neighboring genes can also be included in
      species-/lineage-specific comparisons. We hope that Plastid-LCGbase facilitates
      gene variation (insertion-deletion, translocation and rearrangement) and
      transcription-level studies of plastid genomes. 

PMID- 25378307
TI  - DEEP: a general computational framework for predicting enhancers.
AB  - Transcription regulation in multicellular eukaryotes is orchestrated by a number
      of DNA functional elements located at gene regulatory regions. Some regulatory
      regions (e.g. enhancers) are located far away from the gene they affect.
      Identification of distal regulatory elements is a challenge for the
      bioinformatics research. Although existing methodologies increased the number of
      computationally predicted enhancers, performance inconsistency of computational
      models across different cell-lines, class imbalance within the learning sets and
      ad hoc rules for selecting enhancer candidates for supervised learning, are some
      key questions that require further examination. In this study we developed DEEP,
      a novel ensemble prediction framework. DEEP integrates three components with
      diverse characteristics that streamline the analysis of enhancer's properties in
      a great variety of cellular conditions. In our method we train many individual
      classification models that we combine to classify DNA regions as enhancers or non
      enhancers. DEEP uses features derived from histone modification marks or
      attributes coming from sequence characteristics. Experimental results indicate
      that DEEP performs better than four state-of-the-art methods on the ENCODE data.
      We report the first computational enhancer prediction results on FANTOM5 data
      where DEEP achieves 90.2% accuracy and 90% geometric mean (GM) of specificity and
      sensitivity across 36 different tissues. We further present results derived using
      in vivo-derived enhancer data from VISTA database. DEEP-VISTA, when tested on an
      independent test set, achieved GM of 80.1% and accuracy of 89.64%. DEEP framework
      is publicly available at http://cbrc.kaust.edu.sa/deep/. 

PMID- 25378308
TI  - REBASE--a database for DNA restriction and modification: enzymes, genes and
      genomes.
AB  - REBASE is a comprehensive and fully curated database of information about the
      components of restriction-modification (RM) systems. It contains fully referenced
      information about recognition and cleavage sites for both restriction enzymes and
      methyltransferases as well as commercial availability, methylation sensitivity,
      crystal and sequence data. All genomes that are completely sequenced are analyzed
      for RM system components, and with the advent of PacBio sequencing, the
      recognition sequences of DNA methyltransferases (MTases) are appearing rapidly.
      Thus, Type I and Type III systems can now be characterized in terms of
      recognition specificity merely by DNA sequencing. The contents of REBASE may be
      browsed from the web http://rebase.neb.com and selected compilations can be
      downloaded by FTP (ftp.neb.com). Monthly updates are also available via email. 

PMID- 25378309
TI  - Optimization of transcription factor binding map accuracy utilizing knockout
      mouse models.
AB  - Genome-wide assessment of protein-DNA interaction by chromatin
      immunoprecipitation followed by massive parallel sequencing (ChIP-seq) is a key
      technology for studying transcription factor (TF) localization and regulation of
      gene expression. Signal-to-noise-ratio and signal specificity in ChIP-seq studies
      depend on many variables, including antibody affinity and specificity. Thus far,
      efforts to improve antibody reagents for ChIP-seq experiments have focused mainly
      on generating higher quality antibodies. Here we introduce KOIN (knockout
      implemented normalization) as a novel strategy to increase signal specificity and
      reduce noise by using TF knockout mice as a critical control for ChIP-seq data
      experiments. Additionally, KOIN can identify 'hyper ChIPable regions' as another
      source of false-positive signals. As the use of the KOIN algorithm reduces false
      positive results and thereby prevents misinterpretation of ChIP-seq data, it
      should be considered as the gold standard for future ChIP-seq analyses,
      particularly when developing ChIP-assays with novel antibody reagents.

PMID- 25378310
TI  - BRENDA in 2015: exciting developments in its 25th year of existence.
AB  - The BRENDA enzyme information system (http://www.brenda-enzymes.org/) has
      developed into an elaborate system of enzyme and enzyme-ligand information
      obtained from different sources, combined with flexible query systems and
      evaluation tools. The information is obtained by manual extraction from primary
      literature, text and data mining, data integration, and prediction algorithms.
      Approximately 300 million data include enzyme function and molecular data from
      more than 30,000 organisms. The manually derived core contains 3 million data
      from 77,000 enzymes annotated from 135,000 literature references. Each entry is
      connected to the literature reference and the source organism. They are
      complemented by information on occurrence, enzyme/disease relationships from text
      mining, sequences and 3D structures from other databases, and predicted enzyme
      location and genome annotation. Functional and structural data of more than
      190,000 enzyme ligands are stored in BRENDA. New features improving the
      functionality and analysis tools were implemented. The human anatomy atlas
      CAVEman is linked to the BRENDA Tissue Ontology terms providing a connection
      between anatomical and functional enzyme data. Word Maps for enzymes obtained
      from PubMed abstracts highlight application and scientific relevance of enzymes.
      The EnzymeDetector genome annotation tool and the reaction database BKM-react
      including reactions from BRENDA, KEGG and MetaCyc were improved. The website was
      redesigned providing new query options.

PMID- 25378311
TI  - The tmRNA website.
AB  - The transfer-messenger RNA (tmRNA) and its partner protein SmpB act together in
      resolving problems arising when translating bacterial ribosomes reach the end of
      mRNA with no stop codon. Their genes have been found in nearly all bacterial
      genomes and in some organelles. The tmRNA Website serves tmRNA sequences,
      alignments and feature annotations, and has recently moved to
      http://bioinformatics.sandia.gov/tmrna/. New features include software used to
      find the sequences, an update raising the number of unique tmRNA sequences from
      492 to 1716, and a database of SmpB sequences which are served along with the
      tmRNA sequence from the same organism. 

PMID- 25378312
TI  - T3DB: the toxic exposome database.
AB  - The exposome is defined as the totality of all human environmental exposures from
      conception to death. It is often regarded as the complement to the genome, with
      the interaction between the exposome and the genome ultimately determining one's
      phenotype. The 'toxic exposome' is the complete collection of chronically or
      acutely toxic compounds to which humans can be exposed. Considerable interest in
      defining the toxic exposome has been spurred on by the realization that most
      human injuries, deaths and diseases are directly or indirectly caused by toxic
      substances found in the air, water, food, home or workplace. The Toxin-Toxin
      Target Database (T3DB--www.t3db.ca) is a resource that was specifically designed
      to capture information about the toxic exposome. Originally released in 2010, the
      first version of T3DB contained data on nearly 2900 common toxic substances along
      with detailed information on their chemical properties, descriptions, targets,
      toxic effects, toxicity thresholds, sequences (for both targets and toxins),
      mechanisms and references. To more closely align itself with the needs of
      epidemiologists, toxicologists and exposome scientists, the latest release of
      T3DB has been substantially upgraded to include many more compounds (>3600),
      targets (>2000) and gene expression datasets (>15,000 genes). It now includes
      extensive data on 'normal' toxic compound concentrations in human biofluids as
      well as detailed chemical taxonomies, informative chemical ontologies and a large
      number of referential NMR, MS/MS and GC-MS spectra. This manuscript describes the
      most recent update to the T3DB, which was previously featured in the 2010 NAR
      Database Issue.

PMID- 25378313
TI  - An update on LNCipedia: a database for annotated human lncRNA sequences.
AB  - The human genome is pervasively transcribed, producing thousands of non-coding
      RNA transcripts. The majority of these transcripts are long non-coding RNAs
      (lncRNAs) and novel lncRNA genes are being identified at rapid pace. To
      streamline these efforts, we created LNCipedia, an online repository of lncRNA
      transcripts and annotation. Here, we present LNCipedia 3.0
      (http://www.lncipedia.org), the latest version of the publicly available human
      lncRNA database. Compared to the previous version of LNCipedia, the database grew
      over five times in size, gaining over 90,000 new lncRNA transcripts. Assessment
      of the protein-coding potential of LNCipedia entries is improved with state-of
      the art methods that include large-scale reprocessing of publicly available
      proteomics data. As a result, a high-confidence set of lncRNA transcripts with
      low coding potential is defined and made available for download. In addition, a
      tool to assess lncRNA gene conservation between human, mouse and zebrafish has
      been implemented.

PMID- 25378314
TI  - Epidaurus: aggregation and integration analysis of prostate cancer epigenome.
AB  - Integrative analyses of epigenetic data promise a deeper understanding of the
      epigenome. Epidaurus is a bioinformatics tool used to effectively reveal inter
      dataset relevance and differences through data aggregation, integration and
      visualization. In this study, we demonstrated the utility of Epidaurus in
      validating hypotheses and generating novel biological insights. In particular, we
      described the use of Epidaurus to (i) integrate epigenetic data from prostate
      cancer cell lines to validate the activation function of EZH2 in castration
      resistant prostate cancer and to (ii) study the mechanism of androgen receptor
      (AR) binding deregulation induced by the knockdown of FOXA1. We found that EZH2's
      noncanonical activation function was reaffirmed by its association with active
      histone markers and the lack of association with repressive markers. More
      importantly, we revealed that the binding of AR was selectively reprogramed to
      promoter regions, leading to the up-regulation of hundreds of cancer-associated
      genes including EGFR. The prebuilt epigenetic dataset from commonly used cell
      lines (LNCaP, VCaP, LNCaP-Abl, MCF7, GM12878, K562, HeLa-S3, A549, HePG2) makes
      Epidaurus a useful online resource for epigenetic research. As standalone
      software, Epidaurus is specifically designed to process user customized datasets
      with both efficiency and convenience. 

PMID- 25378315
TI  - Extendable blocking probe in reverse transcription for analysis of RNA variants
      with superior selectivity.
AB  - Here we provide the first strategy to use a competitive Extendable Blocking Probe
      (ExBP) for allele-specific priming with superior selectivity at the stage of
      reverse transcription. In order to analyze highly similar RNA variants, a reverse
      transcriptase primer whose sequence matches a specific variant selectively primes
      only that variant, whereas mismatch priming to the alternative variant is
      suppressed by virtue of hybridization and subsequent extension of the perfectly
      matched ExBP on that alternative variant template to form a cDNA-RNA hybrid. This
      hybrid will render the alternative RNA template unavailable for mismatch priming
      initiated by the specific primer in a hot-start protocol of reverse transcription
      when the temperature decreases to a level where such mismatch priming could
      occur. The ExBP-based reverse transcription assay detected BRAF and KRAS
      mutations in at least 1000-fold excess of wild-type RNA and detection was linear
      over a 4-log dynamic range. This novel strategy not only reveals the presence or
      absence of rare mutations with an exceptionally high selectivity, but also
      provides a convenient tool for accurate determination of RNA variants in
      different settings, such as quantification of allele-specific expression. 

PMID- 25378317
TI  - SnoVectors for nuclear expression of RNA.
AB  - Many long noncoding RNAs (lncRNAs) are constrained to the nucleus to exert their
      functions. However, commonly used vectors that were designed to express mRNAs
      have not been optimized for the study of nuclear RNAs. We reported recently that
      sno-lncRNAs are not capped or polyadenylated but rather are terminated on each
      end by snoRNAs and their associated proteins. These RNAs are processed from
      introns and are strictly confined to the nucleus. Here we have used these
      features to design expression vectors that can stably express virtually any
      sequence of interest and constrain its accumulation to the nucleus. Further,
      these RNAs appear to retain normal nuclear associations and function. SnoVectors
      should be useful in conditions where nuclear RNA function is studied or where
      export to the cytoplasm needs to be avoided. 

PMID- 25378316
TI  - IMGT(r), the international ImMunoGeneTics information system(r) 25 years on.
AB  - IMGT((r)), the international ImMunoGeneTics information
      system((r))(http://www.imgt.org) is the global reference in immunogenetics and
      immunoinformatics. By its creation in 1989 by Marie-Paule Lefranc (Universite de
      Montpellier and CNRS), IMGT((r)) marked the advent of immunoinformatics, which
      emerged at the interface between immunogenetics and bioinformatics. IMGT((r)) is
      specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR),
      major histocompatibility (MH) and proteins of the IgSF and MhSF superfamilies.
      IMGT((r)) is built on the IMGT-ONTOLOGY axioms and concepts, which bridged the
      gap between genes, sequences and 3D structures. The concepts include the
      IMGT((r)) standardized keywords (identification), IMGT((r)) standardized labels
      (description), IMGT((r)) standardized nomenclature (classification), IMGT unique
      numbering and IMGT Colliers de Perles (numerotation). IMGT((r)) comprises 7
      databases, 17 online tools and 15,000 pages of web resources, and provides a high
      quality and integrated system for analysis of the genomic and expressed IG and TR
      repertoire of the adaptive immune responses, including NGS high-throughput data.
      Tools and databases are used in basic, veterinary and medical research, in
      clinical applications (mutation analysis in leukemia and lymphoma) and in
      antibody engineering and humanization. The IMGT/mAb-DB interface was developed
      for therapeutic antibodies and fusion proteins for immunological applications
      (FPIA). IMGT((r)) is freely available at http://www.imgt.org.

PMID- 25378318
TI  - DBTSS as an integrative platform for transcriptome, epigenome and genome sequence
      variation data.
AB  - DBTSS (http://dbtss.hgc.jp/) was originally constructed as a collection of
      uniquely determined transcriptional start sites (TSSs) in humans and some other
      species in 2002. Since then, it has been regularly updated and in recent updates
      epigenetic information has also been incorporated because such information is
      useful for characterizing the biological relevance of these TSSs/downstream
      genes. In the newest release, Release 9, we further integrated public and
      original single nucleotide variation (SNV) data into our database. For our
      original data, we generated SNV data from genomic analyses of various cancer
      types, including 97 lung adenocarcinomas and 57 lung small cell carcinomas from
      Japanese patients as well as 26 cell lines of lung cancer origin. In addition, we
      obtained publically available SNV data from other cancer types and germline
      variations in total of 11,322 individuals. With these updates, users can examine
      the association between sequence variation pattern in clinical lung cancers with
      its corresponding TSS-seq, RNA-seq, ChIP-seq and BS-seq data. Consequently, DBTSS
      is no longer a mere storage site for TSS information but has evolved into an
      integrative platform of a variety of genome activity data. 

PMID- 25378319
TI  - Cyclebase 3.0: a multi-organism database on cell-cycle regulation and phenotypes.
AB  - The eukaryotic cell division cycle is a highly regulated process that consists of
      a complex series of events and involves thousands of proteins. Researchers have
      studied the regulation of the cell cycle in several organisms, employing a wide
      range of high-throughput technologies, such as microarray-based mRNA expression
      profiling and quantitative proteomics. Due to its complexity, the cell cycle can
      also fail or otherwise change in many different ways if important genes are
      knocked out, which has been studied in several microscopy-based knockdown
      screens. The data from these many large-scale efforts are not easily accessed,
      analyzed and combined due to their inherent heterogeneity. To address this, we
      have created Cyclebase--available at http://www.cyclebase.org--an online database
      that allows users to easily visualize and download results from genome-wide cell
      cycle-related experiments. In Cyclebase version 3.0, we have updated the content
      of the database to reflect changes to genome annotation, added new mRNA and
      protein expression data, and integrated cell-cycle phenotype information from
      high-content screens and model-organism databases. The new version of Cyclebase
      also features a new web interface, designed around an overview figure that
      summarizes all the cell-cycle-related data for a gene.

PMID- 25378320
TI  - Functional characterization of C. elegans Y-box-binding proteins reveals tissue
      specific functions and a critical role in the formation of polysomes.
AB  - The cold shock domain is one of the most highly conserved motifs between bacteria
      and higher eukaryotes. Y-box-binding proteins represent a subfamily of cold shock
      domain proteins with pleiotropic functions, ranging from transcription in the
      nucleus to translation in the cytoplasm. These proteins have been investigated in
      all major model organisms except Caenorhabditis elegans. In this study, we set
      out to fill this gap and present a functional characterization of CEYs, the C.
      elegans Y-box-binding proteins. We find that, similar to other organisms, CEYs
      are essential for proper gametogenesis. However, we also report a novel function
      of these proteins in the formation of large polysomes in the soma. In the absence
      of the somatic CEYs, polysomes are dramatically reduced with a simultaneous
      increase in monosomes and disomes, which, unexpectedly, has no obvious impact on
      animal biology. Because transcripts that are enriched in polysomes in wild-type
      animals tend to be less abundant in the absence of CEYs, our findings suggest
      that large polysomes might depend on transcript stabilization mediated by CEY
      proteins.

PMID- 25378321
TI  - A platform for rapid prototyping of synthetic gene networks in mammalian cells.
AB  - Mammalian synthetic biology may provide novel therapeutic strategies, help
      decipher new paths for drug discovery and facilitate synthesis of valuable
      molecules. Yet, our capacity to genetically program cells is currently hampered
      by the lack of efficient approaches to streamline the design, construction and
      screening of synthetic gene networks. To address this problem, here we present a
      framework for modular and combinatorial assembly of functional (multi)gene
      expression vectors and their efficient and specific targeted integration into a
      well-defined chromosomal context in mammalian cells. We demonstrate the potential
      of this framework by assembling and integrating different functional mammalian
      regulatory networks including the largest gene circuit built and chromosomally
      integrated to date (6 transcription units, 27kb) encoding an inducible memory
      device. Using a library of 18 different circuits as a proof of concept, we also
      demonstrate that our method enables one-pot/single-flask chromosomal integration
      and screening of circuit libraries. This rapid and powerful prototyping platform
      is well suited for comparative studies of genetic regulatory elements, genes and
      multi-gene circuits as well as facile development of libraries of isogenic
      engineered cell lines.

PMID- 25378322
TI  - UniPROBE, update 2015: new tools and content for the online database of protein
      binding microarray data on protein-DNA interactions.
AB  - The Universal PBM Resource for Oligonucleotide Binding Evaluation (UniPROBE)
      serves as a convenient source of information on published data generated using
      universal protein-binding microarray (PBM) technology, which provides in vitro
      data about the relative DNA-binding preferences of transcription factors for all
      possible sequence variants of a length k ('k-mers'). The database displays
      important information about the proteins and displays their DNA-binding
      specificity data in terms of k-mers, position weight matrices and graphical
      sequence logos. This update to the database documents the growth of UniPROBE
      since the last update 4 years ago, and introduces a variety of new features and
      tools, including a new streamlined pipeline that facilitates data deposition by
      universal PBM data generators in the research community, a tool that generates
      putative nonbinding (i.e. negative control) DNA sequences for one or more
      proteins and novel motifs obtained by analyzing the PBM data using the BEEML-PBM
      algorithm for motif inference. The UniPROBE database is available at
      http://uniprobe.org. 

PMID- 25378323
TI  - Structure-based predictions broadly link transcription factor mutations to gene
      expression changes in cancers.
AB  - Thousands of unique mutations in transcription factors (TFs) arise in cancers,
      and the functional and biological roles of relatively few of these have been
      characterized. Here, we used structure-based methods developed specifically for
      DNA-binding proteins to systematically predict the consequences of mutations in
      several TFs that are frequently mutated in cancers. The explicit consideration of
      protein-DNA interactions was crucial to explain the roles and prevalence of
      mutations in TP53 and RUNX1 in cancers, and resulted in a higher specificity of
      detection for known p53-regulated genes among genetic associations between TP53
      genotypes and genome-wide expression in The Cancer Genome Atlas, compared to
      existing methods of mutation assessment. Biophysical predictions also indicated
      that the relative prevalence of TP53 missense mutations in cancer is proportional
      to their thermodynamic impacts on protein stability and DNA binding, which is
      consistent with the selection for the loss of p53 transcriptional function in
      cancers. Structure and thermodynamics-based predictions of the impacts of
      missense mutations that focus on specific molecular functions may be increasingly
      useful for the precise and large-scale inference of aberrant molecular phenotypes
      in cancer and other complex diseases.

PMID- 25378324
TI  - Short loop-targeting oligoribonucleotides antagonize Lin28 and enable pre-let-7
      processing and suppression of cell growth in let-7-deficient cancer cells.
AB  - MicroRNAs (miRNAs) originate from stem-loop-containing precursors (pre-miRNAs,
      pri-miRNAs) and mature by means of the Drosha and Dicer endonucleases and their
      associated factors. The let-7 miRNAs have prominent roles in developmental
      differentiation and in regulating cell proliferation. In cancer, the tumor
      suppressor function of let-7 is abrogated by overexpression of Lin28, one of
      several RNA-binding proteins that regulate let-7 biogenesis by interacting with
      conserved motifs in let-7 precursors close to the Dicer cleavage site. Using in
      vitro assays, we have identified a binding site for short modified
      oligoribonucleotides ('looptomirs') overlapping that of Lin28 in pre-let-7a-2.
      These looptomirs selectively antagonize the docking of Lin28, but still permit
      processing of pre-let-7a-2 by Dicer. Looptomirs restored synthesis of mature let
      7 and inhibited growth and clonogenic potential in Lin28 overexpressing
      hepatocarcinoma cells, thereby demonstrating a promising new means to rescue
      defective miRNA biogenesis in Lin28-dependent cancers. 

PMID- 25378325
TI  - Timely binding of IHF and Fis to DARS2 regulates ATP-DnaA production and
      replication initiation.
AB  - In Escherichia coli, the ATP-bound form of DnaA (ATP-DnaA) promotes replication
      initiation. During replication, the bound ATP is hydrolyzed to ADP to yield the
      ADP-bound form (ADP-DnaA), which is inactive for initiation. The chromosomal site
      DARS2 facilitates the regeneration of ATP-DnaA by catalyzing nucleotide exchange
      between free ATP and ADP bound to DnaA. However, the regulatory mechanisms
      governing this exchange reaction are unclear. Here, using in vitro reconstituted
      experiments, we show that two nucleoid-associated proteins, IHF and Fis, bind
      site-specifically to DARS2 to activate coordinately the exchange reaction. The
      regenerated ATP-DnaA was fully active in replication initiation and underwent
      DnaA-ATP hydrolysis. ADP-DnaA formed heteromultimeric complexes with IHF and Fis
      on DARS2, and underwent nucleotide dissociation more efficiently than ATP-DnaA.
      Consistently, mutant analyses demonstrated that specific binding of IHF and Fis
      to DARS2 stimulates the formation of ATP-DnaA production, thereby promoting
      timely initiation. Moreover, we show that IHF-DARS2 binding is temporally
      regulated during the cell cycle, whereas Fis only binds to DARS2 in exponentially
      growing cells. These results elucidate the regulation of ATP-DnaA and replication
      initiation in coordination with the cell cycle and growth phase.

PMID- 25378326
TI  - Genomicus update 2015: KaryoView and MatrixView provide a genome-wide perspective
      to multispecies comparative genomics.
AB  - The Genomicus web server (http://www.genomicus.biologie.ens.fr/genomicus) is a
      visualization tool allowing comparative genomics in four different phyla
      (Vertebrate, Fungi, Metazoan and Plants). It provides access to genomic
      information from extant species, as well as ancestral gene content and gene order
      for vertebrates and flowering plants. Here we present the new features available
      for vertebrate genome with a focus on new graphical tools. The interface to enter
      the database has been improved, two pairwise genome comparison tools are now
      available (KaryoView and MatrixView) and the multiple genome comparison tools
      (PhyloView and AlignView) propose three new kinds of representation and a more
      intuitive menu. These new developments have been implemented for Genomicus portal
      dedicated to vertebrates. This allows the analysis of 68 extant animal genomes,
      as well as 58 ancestral reconstructed genomes. The Genomicus server also provides
      access to ancestral gene orders, to facilitate evolutionary and comparative
      genomics studies, as well as computationally predicted regulatory interactions,
      thanks to the representation of conserved non-coding elements with their putative
      gene targets. 

PMID- 25378327
TI  - The role of G-density in switch region repeats for immunoglobulin class switch
      recombination.
AB  - The boundaries of R-loops are well-documented at immunoglobulin heavy chain loci
      in mammalian B cells. Within primary B cells or B cell lines, the upstream
      boundaries of R-loops typically begin early in the repetitive portion of the
      switch regions. Most R-loops terminate within the switch repetitive zone, but the
      remainder can extend a few hundred base pairs further, where G-density on the non
      template DNA strand gradually drops to the genome average. Whether the G-density
      determines how far the R-loops extend is an important question. We previously
      studied the role of G-clusters in initiating R-loop formation, but we did not
      examine the role of G-density in permitting the elongation of the R-loop, after
      it had initiated. Here, we vary the G-density of different portions of the switch
      region in a murine B cell line. We find that both class switch recombination
      (CSR) and R-loop formation decrease significantly when the overall G-density is
      reduced from 46% to 29%. Short 50 bp insertions with low G-density within switch
      regions do not appear to affect either CSR or R-loop elongation, whereas a longer
      (150 bp) insertion impairs both. These results demonstrate that G-density is an
      important determinant of the length over which mammalian genomic R-loops extend.

PMID- 25378328
TI  - MyMpn: a database for the systems biology model organism Mycoplasma pneumoniae.
AB  - MyMpn (http://mympn.crg.eu) is an online resource devoted to studying the human
      pathogen Mycoplasma pneumoniae, a minimal bacterium causing lower respiratory
      tract infections. Due to its small size, its ability to grow in vitro, and the
      amount of data produced over the past decades, M. pneumoniae is an interesting
      model organisms for the development of systems biology approaches for unicellular
      organisms. Our database hosts a wealth of omics-scale datasets generated by
      hundreds of experimental and computational analyses. These include data obtained
      from gene expression profiling experiments, gene essentiality studies, protein
      abundance profiling, protein complex analysis, metabolic reactions and network
      modeling, cell growth experiments, comparative genomics and 3D tomography. In
      addition, the intuitive web interface provides access to several visualization
      and analysis tools as well as to different data search options. The availability
      and--even more relevant--the accessibility of properly structured and organized
      data are of up-most importance when aiming to understand the biology of an
      organism on a global scale. Therefore, MyMpn constitutes a unique and valuable
      new resource for the large systems biology and microbiology community.

PMID- 25378329
TI  - MatrixDB, the extracellular matrix interaction database: updated content, a new
      navigator and expanded functionalities.
AB  - MatrixDB (http://matrixdb.ibcp.fr) is a freely available database focused on
      interactions established by extracellular proteins and polysaccharides. It is an
      active member of the International Molecular Exchange (IMEx) consortium and has
      adopted the PSI-MI standards for annotating and exchanging interaction data,
      either at the MIMIx or IMEx level. MatrixDB content has been updated by curation
      and by importing extracellular interaction data from other IMEx databases. Other
      major changes include the creation of a new website and the development of a
      novel graphical navigator, iNavigator, to build and expand interaction networks.
      Filters may be applied to build sub-networks based on a list of biomolecules, a
      specified interaction detection method and/or an expression level by tissue,
      developmental stage, and health state (UniGene data). Any molecule of the network
      may be selected and its partners added to the network at any time. Networks may
      be exported under Cytoscape and tabular formats and as images, and may be saved
      for subsequent re-use. 

PMID- 25378330
TI  - Recent improvements to Binding MOAD: a resource for protein-ligand binding
      affinities and structures.
AB  - For over 10 years, Binding MOAD (Mother of All Databases;
      http://www.BindingMOAD.org) has been one of the largest resources for high
      quality protein-ligand complexes and associated binding affinity data. Binding
      MOAD has grown at the rate of 1994 complexes per year, on average. Currently, it
      contains 23,269 complexes and 8156 binding affinities. Our annual updates curate
      the data using a semi-automated literature search of the references cited within
      the PDB file, and we have recently upgraded our website and added new features
      and functionalities to better serve Binding MOAD users. In order to eliminate the
      legacy application server of the old platform and to accommodate new changes, the
      website has been completely rewritten in the LAMP (Linux, Apache, MySQL and PHP)
      environment. The improved user interface incorporates current third-party plugins
      for better visualization of protein and ligand molecules, and it provides
      features like sorting, filtering and filtered downloads. In addition to the field
      based searching, Binding MOAD now can be searched by structural queries based on
      the ligand. In order to remove redundancy, Binding MOAD records are clustered in
      different families based on 90% sequence identity. The new Binding MOAD, with the
      upgraded platform, features and functionalities, is now equipped to better serve
      its users.

PMID- 25378331
TI  - Integrated mechanism for the generation of the 5' junctions of LINE inserts.
AB  - To elucidate the molecular mechanism of the integration of long interspersed
      elements (LINEs), we characterized the 5' ends of more than 200 LINE de novo
      retrotransposition events into chicken DT40 or human HeLa cells. Human L1 inserts
      produced 15-bp target-site duplications (TSDs) and zebrafish ZfL2-1 inserts
      produced 5-bp TSDs in DT40 cells, suggesting that TSD length depends on the LINE
      species. Further analysis of 5' junctions revealed that the 5'-end-joining
      pathways of LINEs can be divided into two fundamental types-annealing or direct.
      We also found that the generation of 5' inversions depends on host and LINE
      species. These results led us to propose a new model for 5'-end joining, the type
      of which is determined by the extent of exposure of 3' overhangs generated after
      the second-strand cleavage and by the involvement of host factors.

PMID- 25378332
TI  - Aberrant transcriptional regulations in cancers: genome, transcriptome and
      epigenome analysis of lung adenocarcinoma cell lines.
AB  - Here we conducted an integrative multi-omics analysis to understand how cancers
      harbor various types of aberrations at the genomic, epigenomic and
      transcriptional levels. In order to elucidate biological relevance of the
      aberrations and their mutual relations, we performed whole-genome sequencing, RNA
      Seq, bisulfite sequencing and ChIP-Seq of 26 lung adenocarcinoma cell lines. The
      collected multi-omics data allowed us to associate an average of 536 coding
      mutations and 13,573 mutations in promoter or enhancer regions with aberrant
      transcriptional regulations. We detected the 385 splice site mutations and 552
      chromosomal rearrangements, representative cases of which were validated to cause
      aberrant transcripts. Averages of 61, 217, 3687 and 3112 mutations are located in
      the regulatory regions which showed differential DNA methylation, H3K4me3,
      H3K4me1 and H3K27ac marks, respectively. We detected distinct patterns of
      aberrations in transcriptional regulations depending on genes. We found that the
      irregular histone marks were characteristic to EGFR and CDKN1A, while a large
      genomic deletion and hyper-DNA methylation were most frequent for CDKN2A. We also
      used the multi-omics data to classify the cell lines regarding their hallmarks of
      carcinogenesis. Our datasets should provide a valuable foundation for biological
      interpretations of interlaced genomic and epigenomic aberrations. 

PMID- 25378333
TI  - The conserved GTPase LepA contributes mainly to translation initiation in
      Escherichia coli.
AB  - LepA is a paralog of EF-G found in all bacteria. Deletion of lepA confers no
      obvious growth defect in Escherichia coli, and the physiological role of LepA
      remains unknown. Here, we identify nine strains (DeltadksA, DeltamolR1,
      DeltarsgA, DeltatatB, DeltatonB, DeltatolR, DeltaubiF, DeltaubiG or DeltaubiH) in
      which DeltalepA confers a synthetic growth phenotype. These strains are
      compromised for gene regulation, ribosome assembly, transport and/or respiration,
      indicating that LepA contributes to these functions in some way. We also use
      ribosome profiling to deduce the effects of LepA on translation. We find that
      loss of LepA alters the average ribosome density (ARD) for hundreds of mRNA
      coding regions in the cell, substantially reducing ARD in many cases. By
      contrast, only subtle and codon-specific changes in ribosome distribution along
      mRNA are seen. These data suggest that LepA contributes mainly to the initiation
      phase of translation. Consistent with this interpretation, the effect of LepA on
      ARD is related to the sequence of the Shine-Dalgarno region. Global perturbation
      of gene expression in the DeltalepA mutant likely explains most of its
      phenotypes.

PMID- 25378334
TI  - Hug1 is an intrinsically disordered protein that inhibits ribonucleotide
      reductase activity by directly binding Rnr2 subunit.
AB  - Rad53 is a conserved protein kinase with a central role in DNA damage response
      and nucleotide metabolism. We observed that the expression of a dominant-lethal
      form of RAD53 leads to significant expression changes for at least 16 genes,
      including the RNR3 and the HUG1 genes, both of which are involved in the control
      of nucleotide metabolism. We established by multiple biophysical and biochemical
      approaches that Hug1 is an intrinsically disordered protein that directly binds
      to the small RNR subunit Rnr2. We characterized the surface of interaction
      involved in Hug1 binding to Rnr2, and we thus defined a new binding region to
      Rnr2. Moreover, we show that Hug1 is deleterious to cell growth in the context of
      reduced RNR activity. This inhibitory effect of Hug1 on RNR activity depends on
      the binding of Hug1 to Rnr2. We propose a model in which Hug1 modulates Rnr2-Rnr1
      association by binding Rnr2. We show that Hug1 accumulates under various
      physiological conditions of high RNR induction. Hence, both the regulation and
      the mode of action of Hug1 are different from those of the small protein
      inhibitors Dif1 and Sml1, and Hug1 can be considered as a regulator for fine
      tuning of RNR activity.

PMID- 25378335
TI  - MeT-DB: a database of transcriptome methylation in mammalian cells.
AB  - Methyltranscriptome is an exciting new area that studies the mechanisms and
      functions of methylation in transcripts. The MethylTranscriptome DataBase (MeT
      DB, http://compgenomics.utsa.edu/methylation/) is the first comprehensive
      resource for N6-methyladenosine (m(6)A) in mammalian transcriptome. It includes a
      database that records publicaly available data sets from methylated RNA
      immunoprecipitation sequencing (MeRIP-Seq), a recently developed technology for
      interrogating m(6)A methyltranscriptome. MeT-DB includes ~ 300 k m(6)A
      methylation sites in 74 MeRIP-Seq samples from 22 different experimental
      conditions predicted by exomePeak and MACS2 algorithms. To explore this rich
      information, MeT-DB also provides a genome browser to query and visualize context
      specific m(6)A methylation under different conditions. MeT-DB also includes the
      binding site data of microRNA, splicing factor and RNA binding proteins in the
      browser window for comparison with m(6)A sites and for exploring the potential
      functions of m(6)A. Analysis of differential m(6)A methylation and the related
      differential gene expression under two conditions is also available in the
      browser. A global perspective of the genome-wide distribution of m(6)A
      methylation in all the data is provided in circular ideograms, which also act as
      a navigation portal. The query results and the entire data set can be exported to
      assist publication and additional analysis.

PMID- 25378336
TI  - The GOA database: gene Ontology annotation updates for 2015.
AB  - The Gene Ontology Annotation (GOA) resource (http://www.ebi.ac.uk/GOA) provides
      evidence-based Gene Ontology (GO) annotations to proteins in the UniProt
      Knowledgebase (UniProtKB). Manual annotations provided by UniProt curators are
      supplemented by manual and automatic annotations from model organism databases
      and specialist annotation groups. GOA currently supplies 368 million GO
      annotations to almost 54 million proteins in more than 480,000 taxonomic groups.
      The resource now provides annotations to five times the number of proteins it did
      4 years ago. As a member of the GO Consortium, we adhere to the most up-to-date
      Consortium-agreed annotation guidelines via the use of quality control checks
      that ensures that the GOA resource supplies high-quality functional information
      to proteins from a wide range of species. Annotations from GOA are freely
      available and are accessible through a powerful web browser as well as a variety
      of annotation file formats.

PMID- 25378337
TI  - APASdb: a database describing alternative poly(A) sites and selection of
      heterogeneous cleavage sites downstream of poly(A) signals.
AB  - Increasing amounts of genes have been shown to utilize alternative
      polyadenylation (APA) 3'-processing sites depending on the cell and tissue type
      and/or physiological and pathological conditions at the time of processing, and
      the construction of genome-wide database regarding APA is urgently needed for
      better understanding poly(A) site selection and APA-directed gene expression
      regulation for a given biology. Here we present a web-accessible database, named
      APASdb (http://mosas.sysu.edu.cn/utr), which can visualize the precise map and
      usage quantification of different APA isoforms for all genes. The datasets are
      deeply profiled by the sequencing alternative polyadenylation sites (SAPAS)
      method capable of high-throughput sequencing 3'-ends of polyadenylated
      transcripts. Thus, APASdb details all the heterogeneous cleavage sites downstream
      of poly(A) signals, and maintains near complete coverage for APA sites, much
      better than the previous databases using conventional methods. Furthermore,
      APASdb provides the quantification of a given APA variant among transcripts with
      different APA sites by computing their corresponding normalized-reads, making our
      database more useful. In addition, APASdb supports URL-based retrieval, browsing
      and display of exon-intron structure, poly(A) signals, poly(A) sites location and
      usage reads, and 3'-untranslated regions (3'-UTRs). Currently, APASdb involves
      APA in various biological processes and diseases in human, mouse and zebrafish. 

PMID- 25378338
TI  - HIV-1, human interaction database: current status and new features.
AB  - The 'Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database',
      available through the National Library of Medicine at
      http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions,
      serves the scientific community exploring the discovery of novel HIV vaccine
      candidates and therapeutic targets. Each HIV-1 human protein interaction can be
      retrieved without restriction by web-based downloads and ftp protocols and
      includes: Reference Sequence (RefSeq) protein accession numbers, National Center
      for Biotechnology Information Gene identification numbers, brief descriptions of
      the interactions, searchable keywords for interactions and PubMed identification
      numbers (PMIDs) of journal articles describing the interactions. In addition to
      specific HIV-1 protein-human protein interactions, included are interaction
      effects upon HIV-1 replication resulting when individual human gene expression is
      blocked using siRNA. A total of 3142 human genes are described participating in
      12,786 protein-protein interactions, along with 1316 replication interactions
      described for each of 1250 human genes identified using small interfering RNA
      (siRNA). Together the data identifies 4006 human genes involved in 14,102
      interactions. With the inclusion of siRNA interactions we introduce a redesigned
      web interface to enhance viewing, filtering and downloading of the combined data
      set.

PMID- 25378339
TI  - Amplicon rearrangements during the extrachromosomal and intrachromosomal
      amplification process in a glioma.
AB  - The mechanisms of gene amplification in tumour cells are poorly understood and
      the relationship between extrachromosomal DNA molecules, named double minutes
      (dmins), and intrachromosomal homogeneously staining regions (hsr) is not
      documented at nucleotide resolution. Using fluorescent in situ hybridization and
      whole genome sequencing, we studied a xenografted human oligodendroglioma where
      the co-amplification of the EGFR and MYC loci was present in the form of dmins at
      early passages and of an hsr at later passages. The amplified regions underwent
      multiple rearrangements and deletions during the formation of the dmins and their
      transformation into hsr. In both forms of amplification, non-homologous end
      joining and microhomology-mediated end-joining rather than replication repair
      mechanisms prevailed in fusions. Small fragments, some of a few tens of base
      pairs, were associated in contigs. They came from clusters of breakpoints
      localized hundreds of kilobases apart in the amplified regions. The
      characteristics of some pairs of junctions suggest that at least some fragments
      were not fused randomly but could result from the concomitant repair of
      neighbouring breakpoints during the interaction of remote DNA sequences. This
      characterization at nucleotide resolution of the transition between extra- and
      intrachromosome amplifications highlights a hitherto uncharacterized organization
      of the amplified regions suggesting the involvement of new mechanisms in their
      formation.

PMID- 25378340
TI  - Europe PMC: a full-text literature database for the life sciences and platform
      for innovation.
AB  - This article describes recent developments of Europe PMC (http://europepmc.org),
      the leading database for life science literature. Formerly known as UKPMC, the
      service was rebranded in November 2012 as Europe PMC to reflect the scope of the
      funding agencies that support it. Several new developments have enriched Europe
      PMC considerably since then. Europe PMC now offers RESTful web services to access
      both articles and grants, powerful search tools such as citation-count sort order
      and data citation features, a service to add publications to your ORCID, a
      variety of export formats, and an External Links service that enables any related
      resource to be linked from Europe PMC content. 

PMID- 25378341
TI  - diArk--the database for eukaryotic genome and transcriptome assemblies in 2014.
AB  - Eukaryotic genomes are the basis for understanding the complexity of life from
      populations to the molecular level. Recent technological innovations have
      revolutionized the speed of data generation enabling the sequencing of eukaryotic
      genomes and transcriptomes within days. The database diArk (http://www.diark.org)
      has been developed with the aim to provide access to all available assembled
      genomes and transcriptomes. In September 2014, diArk contains about 2600
      eukaryotes with 6000 genome and transcriptome assemblies, of which 22% are not
      available via NCBI/ENA/DDBJ. Several indicators for the quality of the assemblies
      are provided to facilitate their comparison for selecting the most appropriate
      dataset for further studies. diArk has a user-friendly web interface with
      extensive options for filtering and browsing the sequenced eukaryotes. In this
      new version of the database we have also integrated species, for which
      transcriptome assemblies are available, and we provide more analyses of
      assemblies. 

PMID- 25378343
TI  - The Eukaryotic Promoter Database: expansion of EPDnew and new promoter analysis
      tools.
AB  - We present an update of EPDNew (http://epd.vital-it.ch), a recently introduced
      new part of the Eukaryotic Promoter Database (EPD) which has been described in
      more detail in a previous NAR Database Issue. EPD is an old database of
      experimentally characterized eukaryotic POL II promoters, which are conceptually
      defined as transcription initiation sites or regions. EPDnew is a collection of
      automatically compiled, organism-specific promoter lists complementing the old
      corpus of manually compiled promoter entries of EPD. This new part is exclusively
      derived from next generation sequencing data from high-throughput promoter
      mapping experiments. We report on the recent growth of EPDnew, its extension to
      additional model organisms and its improved integration with other bioinformatics
      resources developed by our group, in particular the Signal Search Analysis and
      ChIP-Seq web servers. 

PMID- 25378342
TI  - G-triplex structure and formation propensity.
AB  - The occurrence of a G-triplex folding intermediate of thrombin binding aptamer
      (TBA) has been recently predicted by metadynamics calculations, and
      experimentally supported by Nuclear Magnetic Resonance (NMR), Circular Dichroism
      (CD) and Differential Scanning Calorimetry (DSC) data collected on a 3' end TBA
      truncated 11-mer oligonucleotide (11-mer-3'-t-TBA). Here we present the solution
      structure of 11-mer-3'-t-TBA in the presence of potassium ions. This structure is
      the first experimental example of a G-triplex folding, where a network of
      Hoogsteen-like hydrogen bonds stabilizes six guanines to form two G:G:G triad
      planes. The G-triplex folding of 11-mer-3'-t-TBA is stabilized by the potassium
      ion and destabilized by increasing the temperature. The superimposition of the
      experimental structure with that predicted by metadynamics shows a great
      similarity, with only significant differences involving two loops. These new
      structural data show that 11-mer-3'-t-TBA assumes a G-triplex DNA conformation as
      its stable form, reinforcing the idea that G-triplex folding intermediates may
      occur in vivo in human guanine-rich sequences. NMR and CD screening of eight
      different constructs obtained by removing from one to four bases at either the 3'
      and the 5' ends show that only the 11-mer-3'-t-TBA yields a relatively stable G
      triplex.

PMID- 25378344
TI  - Indirect payments from drug companies to doctors for CME courses will be exempt
      from database.

PMID- 25378345
TI  - Glutathione S-transferase M1 and glutathione S-transferase T1 genotype in chronic
      pancreatitis: a meta-analysis.
AB  - OBJECTIVE: A meta-analysis to determine the association between chronic
      pancreatitis and glutathione-S transferase (GST) mu 1 (GSTM1) and theta 1 (GSTT1)
      deletions. METHODS: Case-control studies concerning the relationship between
      chronic pancreatitis and GSTM1 or GSTT1 deletions were identified (up to October
      2013). Meta-analyses of the association between GSTM1 and GSTT1 genotype and
      chronic pancreatitis or alcoholic chronic pancreatitis (ACP) were performed.
      RESULTS: Seven studies were included in the meta-analysis (650 patients/1382
      controls for GSTM1 and 536 patients/1304 controls for GSTT1). There were no
      significant relationships between GSTM1/GSTT1 and chronic pancreatitis or GSTT1
      and ACP. There was a significant association between GSTM1 null genotype and ACP
      (odds ratio 1.16, 95% confidence intervals 1.03, 1.30). CONCLUSION: The GSTM1
      null genotype was significantly associated with ACP risk.

PMID- 25378346
TI  - Clinical value of repeat blood cultures in neonatal patients receiving antibiotic
      treatment.
AB  - OBJECTIVE: Retrospective database study to determine the clinical usefulness of
      repeat blood cultures in antibiotic-treated neonates. METHODS: Data regarding
      blood culture indication and findings for patients admitted to a neonatal
      intensive care unit (NICU) over a 2-year period were obtained from the hospital
      database. Repeat blood culture was defined as culture performed <7 days from
      initial testing in a patient receiving antibiotic treatment. RESULTS: Repeat
      cultures made up 21.3% of all blood cultures originating in the NICU (500/2352
      cultures; 338 initial positive cultures; 210 patients). The most common
      indications for repeat culture were follow-up of clinically well babies with
      previous positive culture findings and the development of new symptoms. The
      majority of culture findings were negative (60.2%), with 7.2% indicating the
      presence of a new pathogen. Cultures repeated on day 5 were significantly more
      likely to reveal a new pathogen than those repeated on days 1-4. CONCLUSIONS:
      Repeat blood cultures in neonatal patients who have developed new symptoms >4
      days after initial testing may be beneficial. The use of repeat blood culture is
      not recommended for any other indication.

PMID- 25378347
TI  - The impact of the peritoneal glucose load index on hydration status and
      inflammation in peritoneal dialysis patients.
AB  - OBJECTIVE: To evaluate the impact of the peritoneal glucose load (PGL) on
      hydration status and inflammation in peritoneal dialysis (PD) patients. METHODS:
      This cross-sectional study evaluated stable PD patients using a novel PGL index
      (PGLI), which was calculated as the net glucose content (g) in the PD solutions
      administered in the daily PD prescription divided by the dry body weight (kg)
      assessed by whole-body bioimpedance spectroscopy. The relationship between PGLI
      and glycosylated haemoglobin (HbA1c), fluid overload (FO), and inflammatory
      markers was investigated. RESULTS: A total of 43 stable PD patients participated
      in the study. Significant positive correlations were found between PGLI and
      HbA1c, FO, plasma high sensitivity C-reactive protein (hsCRP), and plasma
      interleukin-6 (IL-6) levels. HbA1c, FO, plasma hsCRP and plasma IL-6 levels were
      significantly higher in patients with PGLI >3 g/kg/day compared with those with
      PGLI <=3 g/kg/day. CONCLUSIONS: PGLI values >3 g/kg/day may be associated with
      poor glycaemic control, over hydration and augmented inflammation. PGLI might be
      a useful tool for the quantitative assessment of the PGL and could be applied
      when managing PD patients.

PMID- 25378348
TI  - Outcomes of prenatally diagnosed lung lesions in multigestational pregnancies.
AB  - BACKGROUND: The outcomes of prenatally diagnosed lung lesions in the context of
      multigestational pregnancies are unknown. METHODS: Of 960 fetal lung lesion cases
      evaluated at a single tertiary center over 16 years, 30 occurred in
      multigestational pregnancies. We reviewed this series to aid in prenatal
      counseling of affected families and to provide prognostic information for
      decision making. Pre- and postnatal clinical characteristics were gathered for
      these pregnancies, and the morbidity and mortality were determined for both
      affected and normal fetuses, whether twins or triplets. RESULTS: Mortality was
      found to be 3/30 (10%) for affected fetuses, and morbidity in normal co-twins was
      consistent with the degree of prematurity. No morbidity was seen in co-twins born
      at or after 36 weeks of gestation. Median gestational age at delivery was 35 5/7
      weeks. CONCLUSIONS: Outcomes for the affected fetus correlate with the size and
      pathophysiologic consequences of the lesion and are not worse than previously
      reported outcomes for similar lesions in singleton pregnancies, while morbidity
      in the normal co-twin is consistent with prematurity related to the fetal age of
      the multiple gestation at delivery, irrespective of the fetal lung lesion.

PMID- 25378350
TI  - Clive Peedell: Pet hate is the "yes men" in medicine.

PMID- 25378349
TI  - TGFbeta responsive tyrosine phosphatase promotes rheumatoid synovial fibroblast
      invasiveness.
AB  - OBJECTIVE: In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) that
      line joint synovial membranes aggressively invade the extracellular matrix,
      destroying cartilage and bone. As signal transduction in FLS is mediated through
      multiple pathways involving protein tyrosine phosphorylation, we sought to
      identify protein tyrosine phosphatases (PTPs) regulating the invasiveness of RA
      FLS. We describe that the transmembrane receptor PTPkappa (RPTPkappa), encoded by
      the transforming growth factor (TGF) beta-target gene, PTPRK, promotes RA FLS
      invasiveness. METHODS: Gene expression was quantified by quantitative PCR. PTP
      knockdown was achieved using antisense oligonucleotides. FLS invasion and
      migration were assessed in transwell or spot assays. FLS spreading was assessed
      by immunofluorescence microscopy. Activation of signalling pathways was analysed
      by Western blotting of FLS lysates using phosphospecific antibodies. In vivo FLS
      invasiveness was assessed by intradermal implantation of FLS into nude mice. The
      RPTPkappa substrate was identified by pull-down assays. RESULTS: PTPRK expression
      was higher in FLS from patients with RA versus patients with osteoarthritis,
      resulting from increased TGFB1 expression in RA FLS. RPTPkappa knockdown impaired
      RA FLS spreading, migration, invasiveness and responsiveness to platelet-derived
      growth factor, tumour necrosis factor and interleukin 1 stimulation. Furthermore,
      RPTPkappa deficiency impaired the in vivo invasiveness of RA FLS. Molecular
      analysis revealed that RPTPkappa promoted RA FLS migration by dephosphorylation
      of the inhibitory residue Y527 of SRC. CONCLUSIONS: By regulating phosphorylation
      of SRC, RPTPkappa promotes the pathogenic action of RA FLS, mediating cross
      activation of growth factor and inflammatory cytokine signalling by TGFbeta in RA
      FLS.

PMID- 25378351
TI  - Differentiation of classical swine fever virus infection from CP7_E2alf marker
      vaccination by a multiplex microsphere immunoassay.
AB  - Classical swine fever (CSF) is a highly contagious viral disease of pigs that has
      a tremendous socioeconomic impact. Vaccines are available for disease control.
      However, most industrialized countries are implementing stamping-out strategies
      to eliminate the disease and avoid trade restrictions. These restrictions can be
      avoided through the use of marker vaccines such as CP7_E2alf. Marker vaccines
      have to be accompanied by reliable and robust discriminatory assays. In this
      context, a multiplex microsphere immunoassay for serological differentiation of
      infected from vaccinated animals (DIVA) was developed to distinguish CSF virus
      (CSFV)-infected animals from CP7_E2alf-vaccinated animals. To this end, three
      viral proteins, namely, CSFV E2, CSFV E(rns), and bovine viral diarrhea virus
      (BVDV) E2, were produced in insect cells using a baculovirus expression system;
      they were used as antigens in a microsphere immunoassay, which was further
      evaluated by testing a large panel of pig sera and compared to a well
      characterized commercial CSFV E2 antibody enzyme-linked immunosorbent assays
      (ELISAs) and a test version of an improved CSFV E(rns) antibody ELISA. Under a
      cutoff median fluorescence intensity value of 5,522, the multiplex microsphere
      immunoassay had a sensitivity of 98.5% and a specificity of 98.9% for the
      detection of antibodies against CSFV E2. The microsphere immunoassay and the CSFV
      E(rns) ELISA gave the same results for 155 out of 187 samples (82.8%) for the
      presence of CSFV E(rns) antibodies. This novel multiplex immunoassay is a
      valuable tool for measuring and differentiating immune responses to vaccination
      and/or infection in animals. 

PMID- 25378354
TI  - Multicomponent treatment for food selectivity in children: description and case
      report.
AB  - BACKGROUND: Food selectivity is common in children with and without developmental
      disabilities and can have negative implications for nutrition intake and family
      quality of life. The evidence base for effective treatment protocols is still
      developing. METHODS: The purpose of this study was to describe a pilot,
      multicomponent treatment protocol for food selectivity and present several case
      examples using a retrospective chart review. Elements in the treatment manual
      included sensory integration and behavioral modification strategies, including
      systematic desensitization. Also, parents were educated on factors associated
      with food selectivity and strategies for increasing food acceptance during family
      meals. RESULTS: Four children with food selectivity demonstrated increased food
      acceptance of previously refused foods. Incidence of negative behaviors,
      including gagging, vomiting, and aggressive behavior (eg, hitting, batting away
      spoon), during clinical meals was also evaluated. No aggressive behavior or
      vomiting was observed during treatment sessions, and gagging on foods at initial
      introduction was minimal. CONCLUSIONS: This descriptive study and case review
      provides information to inform treatment of food selectivity and may provide a
      catalyst for larger scale clinical trials.

PMID- 25378352
TI  - Immunogenicity of a bovine herpesvirus 1 glycoprotein D DNA vaccine complexed
      with bovine neutrophil beta-defensin 3.
AB  - Protective efficacy against bovine herpesvirus 1 (BoHV-1) has been demonstrated
      to be induced by a plasmid encoding bovine neutrophil beta-defensin 3 (BNBD3) as
      a fusion construct with truncated glycoprotein D (tgD). However, in spite of the
      increased cell-mediated immune responses induced by this DNA vaccine, the
      clinical responses of BoHV-1-challenged cattle were not reduced over those
      observed in animals vaccinated with the plasmid encoding tgD alone; this might
      have been because the vaccine failed to improve humoral responses. We
      hypothesized that an alternative vaccine design strategy that utilized the DNA
      vaccine pMASIA-tgD as a complex with BNBD3 might improve humoral responses while
      maintaining robust Th1-type cell-mediated responses. C57BL/6 mice were vaccinated
      with pMASIA-tgD complexed with 0, 0.01875, 0.1875, or 1.875 nmol of a stable
      synthesized analog of BNBD3 (aBNBD3). The best results were seen in mice
      immunized with the vaccine composed of pMASIA-tgD complexed to 0.1875 nmol
      aBNBD3. In this group, humoral responses were improved, as evidenced by increased
      virus neutralization, tgD-specific early IgG1, and later IgG2a titers, while the
      strong cell-mediated immune responses, measured based on specific gamma
      interferon (IFN-gamma)-secreting cells, were maintained relative to pMASIA-tgD.
      Modulation of the immune response might have been due in part to the effect of
      BNBD3 on dendritic cells (DCs). In vitro studies showed that murine bone marrow
      derived DCs (BMDCs) pretreated with aBNBD3 were activated, as evidenced by CD11c
      downregulation, and were functionally mature, as shown by increased
      allostimulatory ability. Native, synthetic, and analog forms of BNBD3 were
      equally capable of inducing functional maturation of BMDCs. 

PMID- 25378355
TI  - Comparison of complication rates, types, and average tube patency between
      jejunostomy tubes and percutaneous gastrostomy tubes in a regional home enteral
      nutrition support program.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are common enteral
      access devices for long-term enteral nutrition. Jejunostomy tubes (J-tubes) are
      able to provide postpyloric enteral access in patients who are not PEG tube
      candidates. There is a scarcity of literature comparing complication rates of J
      tubes to PEG tubes. OBJECTIVE: To compare and characterize J-tube and PEG tube
      complications requiring tube replacement. METHODS: A retrospective chart review
      was performed on 560 patients discharged from the Northern Alberta Home Enteral
      Nutrition Support Program (NAHENSP) from January 2010 to December 2011. Patients
      were followed for 3 years from initial tube insertion or until discharge from the
      NAHENSP, whichever was earliest. Comparisons were made in terms of complications
      requiring tube replacement, tube patency to first replacement, and indications
      for tube replacement. RESULTS: A total of 64 J-tube patients were identified and
      compared with 65 PEG tube patients. Tube replacement rates for the J-tube group
      included 3.2 cases per 1000 patient days compared with 0.86 cases per 1000
      patient days in the PEG group (P < .001). The mean +/- SEM duration to first tube
      replacement for J-tube and PEG tube patients was 160 +/- 26.3 days and 331 +/-
      53.6 days, respectively (P = .010). The most common causes for tube replacement
      in J-tube patients were dislodgement (35.6%) and obstruction (22.2%) compared
      with routine replacement (54.5%) and dislodgement (27.2%) in the PEG tube group.
      CONCLUSION: J-tubes are associated with higher complication rates requiring tube
      replacement compared with PEG tubes. The main causes of J-tube replacement are
      dislodgement and obstruction.

PMID- 25378356
TI  - Growth failure and nutrition considerations in chronic childhood wasting
      diseases.
AB  - Growth failure is a common problem in many children with chronic diseases. This
      article is an overview of the most common causes of growth failure/growth
      retardation that affect children with a number of chronic diseases. We also
      briefly review the nutrition considerations and treatment goals. Growth failure
      is multifactorial in children with chronic conditions, including patients with
      cystic fibrosis, chronic kidney disease, chronic liver disease, congenital heart
      disease, human immunodeficiency virus, inflammatory bowel disease, short bowel
      syndrome, and muscular dystrophies. Important contributory factors to growth
      failure include increased energy needs, increased energy loss, malabsorption,
      decreased energy intake, anorexia, pain, vomiting, intestinal obstruction, and
      inflammatory cytokines. Various metabolic and pathologic abnormalities that are
      characteristic of chronic diseases further lead to significant malnutrition and
      growth failure. In addition to treating disease-specific abnormalities, treatment
      should address the energy and protein deficits, including vitamin and mineral
      supplements to correct deficiencies, correct metabolic and endocrinologic
      abnormalities, and include long-term monitoring of weight and growth.
      Individualized, age-appropriate nutrition intervention will minimize the
      malnutrition and growth failure seen in children with chronic diseases. 

PMID- 25378357
TI  - Exploring the link between industry payments to doctors and prescribing habits.

PMID- 25378353
TI  - Intraocular levels of interleukin 17A (IL-17A) and IL-10 as respective
      determinant markers of toxoplasmosis and viral uveitis.
AB  - Uveitis is a potentially blinding inflammatory disease. Thirty to 50% of uveitis
      cases are considered idiopathic. The present study sought to determine the
      intraocular cytokine patterns in the different etiological types of uveitis in
      order to better understand their immunological regulation and to determine
      whether the cytokine pattern may be a useful diagnostic tool. From a multicenter
      institutional prospective study, the clinical and biological data from patients
      with uveitis of various etiologies, determined after a complete workup, were
      compared with those from a control group of cataract patients. A multiplex assay
      was used to assess the profiles of 27 cytokines and chemokines in aqueous humor
      samples from these patients. In total, 62 patients with infectious or
      noninfectious uveitis and 88 controls were included. After a complete workup, the
      cause of uveitis remained unknown in 25 patients (40% idiopathic uveitis).
      Interleukin 1beta (IL-1beta) levels were markedly increased in viral uveitis, as
      were IL-10 levels, whereas IL-17A levels were augmented in toxoplasmic uveitis.
      Based on the cytokine pattern, the patients were reassigned to specific groups.
      At the end of the study, the diagnosis of idiopathic uveitis was still valid in
      only 11 patients (18%). The observation that some markers are specific to certain
      diseases enables a better understanding of the disease pathogenesis and paves the
      way for new diagnostic methods aimed to identify inflammatory markers, which may
      perhaps be targeted by therapy. 

PMID- 25378358
TI  - Geriatric assessment for therapeutic decision-making regarding renal replacement
      in elderly patients with advanced chronic kidney disease.
AB  - In patients older than 75 years with advanced chronic kidney disease (CKD), the
      decision between treatment with dialysis [intention to treat with dialysis (ITD)]
      or conservative care (CC) is a challenge. Geriatric assessment can be helpful.
      The aim was to identify which factors had had an influence on decision-making.
      METHODS: We recruited 56 patients. At baseline we analyzed age, frailty (defined
      following the criteria of Fried et al. [J Gerontol A Biol Sci Med Sci 2001;56:146
      156]), dependence for activities of daily living (ADL), cognitive impairment,
      depression, comorbidity, cardiovascular disease, and diabetes. After full
      information about prognosis and treatment options, the preferences of the
      patients and families were taken into consideration as determinants in the
      decision-making process. During the follow-up, we evaluated clinical and
      laboratory parameters, hospitalization, mortality and reevaluated frailty.
      RESULTS: Twenty patients opted for CC, and 36 patients opted for ITD. On
      univariate analysis, the predictive factors of the election of CC were age,
      prefrailty, cognitive impairment, and dependence for ADL. In the multivariate
      analysis, age and prefrailty remained as predictors for the choice of CC.
      Hospitalizations were more frequent in CC. Survival was similar in both groups (p
      = 0.098). CONCLUSIONS: Frailty assessment could be useful for decision-making
      about the treatment in elderly patients with CKD. CC may be a good treatment
      option.

PMID- 25378359
TI  - Amyotrophic Lateral Sclerosis Genetic Studies: From Genome-wide Association
      Mapping to Genome Sequencing.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of obscure
      etiology. Multiple genetic studies have been conducted to advance our
      understanding of the disease, employing a variety of techniques such as linkage
      mapping in families, to genome-wide association studies and sequencing based
      approaches such as whole exome sequencing and whole genome sequencing and a few
      epigenetic analyses. While major progress has been made, the majority of the
      genetic variation involved in ALS is yet to be undefined. The optimal study
      designs to investigate ALS depend on the genetic model for the disease, and it is
      likely that different approaches will be required to map genes involved in
      familial and sporadic disease. The potential approaches and their strengths and
      weaknesses are discussed. 

PMID- 25378360
TI  - Minimally invasive atrial septal defect closure: what is that?

PMID- 25378361
TI  - Paediatric subvalvular aortic stenosis: a systematic review and meta-analysis of
      natural history and surgical outcome.
AB  - Sub-valvular aortic stenosis (SAS) is a common form of left ventricular outflow
      tract (LVOT) obstruction, which can lead to aortic valve damage. Although surgery
      for SAS is an accepted treatment, the timing of surgical intervention of SAS
      remains controversial. This review aims to establish an overview of the natural
      history and outcome after surgery and factors associated with prognosis in
      paediatric SAS patients. We searched PubMed and EMBASE for studies that reported
      factors that negatively affected the prognosis of patients with SAS. Studies were
      included if they were written in English, published between 1 January 1997 and 31
      December 2012 and the mean patient age was <18 years at the time of study entry.
      Studies were excluded if the study size was <20 patients. A distinction was made
      between natural history and surgical cohorts. Twenty-four studies were included
      in this review, encompassing a total of 809 natural history and 1476 surgical
      patients. Fifty-one percent of natural history patients required surgery. After
      surgery, there was a substantial reoperation rate. Higher LVOT gradient and the
      presence of aortic regurgitation (AR) were identified as the foremost independent
      predictors of a worse outcome. Valve-to-membrane distance was also found to be
      associated with prognosis, although the results were contradictory. This
      systematic review underlines the importance of LVOT gradient, aortic valve-to
      membrane distance and AR in surgical decision-making in paediatric SAS patients.
      There is need for collaborative effort to further study the optimal timing of
      surgery based on LVOT gradient, valve-to-membrane distance and the presence of
      AR. 

PMID- 25378362
TI  - Surgeon-specific mortality data: bury your head in the sand.

PMID- 25378363
TI  - Outcomes of mitral valve repair compared with replacement in patients undergoing
      concomitant aortic valve surgery: a meta-analysis of observational studies.
AB  - Long-term superiority of mitral valve (MV) repair compared with replacement is
      well established in degenerative MV disease. In rheumatic heart disease, its
      advantages are unclear and it is often performed in conjunction with aortic valve
      (AV) replacement. Herein, we performed a systematic review and meta-analysis
      comparing outcomes of MV repair vs replacement in patients undergoing concomitant
      AV replacement. PubMed, Cochrane and Web of Science databases were searched up to
      25 January 2014 for English language studies comparing outcomes of MV repair vs
      replacement in patients undergoing simultaneous AV replacement. Data of selected
      studies were extracted. Study quality, publication bias and heterogeneity were
      assessed. Analysis was performed using a random effects model (meta-analysis of
      observational studies in epidemiology recommendation). A total of 1202
      abstracts/titles were screened. Of these, 20 were selected for full text review
      and 8 studies (3924 patients) were included in the final analysis: 1255 underwent
      MV repair and 2669 underwent replacement. Late outcome data were available in
      seven studies (cumulative follow-up: 15 654 patient-years). The early (in
      hospital and up to 30 days post-surgery) mortality [risk ratio (RR): 0.68, 95%
      confidence interval (CI): 0.53-0.87, P = 0.003] and late (>30 days post-surgery)
      mortality (RR: 0.76, 95% CI: 0.64-0.90 P = 0.001) were significantly lower in the
      MV repair group compared with the MV replacement group. The MV reoperation rate
      (RR: 1.89, 95% CI: 0.87-4.10, P = 0.108), thromboembolism (including valve
      thrombosis) (RR: 0.65, 95% CI: 0.38-1.13, P = 0.128) and major bleeding rates
      (RR: 0.88, 95% CI: 0.49-1.57, P = 0.659) were found to be comparable between the
      two groups. In a separate analysis of studies with exclusively rheumatic patients
      (n = 1106), the early as well as late mortality benefit of MV repair was lost
      (RR: 0.92, 95% CI: 0.44-1.90, P = 0.81 and RR: 0.69, 95% CI: 0.39-1.22, P =
      0.199, respectively), whereas the MV reoperation rate became significantly higher
      (RR: 5.10, 95% CI: 1.62-16.05, P = 0.005) with MV repair. In patients undergoing
      concomitant mitral and AV surgery, MV repair is associated with improved early
      and late survival without any increased risk for mitral valve reoperation.
      However, in patients with rheumatic heart disease MV repair does not impart any
      survival advantage while the risk for MV reoperation remains significantly
      higher. 

PMID- 25378364
TI  - Impact of residual right ventricular outflow tract obstruction on biventricular
      strain and synchrony in patients after repair of tetralogy of Fallot: a cardiac
      magnetic resonance feature tracking study.
AB  - OBJECTIVES: Residual right ventricular outflow tract (RVOT) obstruction (RVOTO)
      is considered beneficial in patients after repair of tetralogy of Fallot (TOF)
      although underlying mechanisms are unknown. We sought to elucidate differences in
      myocardial strain and dyssynchrony parameters in patients after TOF repair with
      and without residual RVOTO using cardiovascular magnetic resonance (CMR) feature
      tracking (CMR-FT) analysis. METHODS: Fifty-four patients (mean age 16.4 +/- 8.4
      years) were assessed by CMR 14.2 +/- 7.3 years after repair of TOF. Residual
      RVOTO on echocardiography was defined as a peak systolic RVOT gradient >25 mmHg
      and was present in 27 patients (no RVOTO in n = 27 patients). Right ventricular
      (RV) and left ventricular (LV) strain measurements were performed using CMR-FT
      software. RESULTS: The two groups were well matched for age at CMR scan, time and
      type of surgical repair. There was no difference in the degree of pulmonary
      regurgitation (PR) and RV end-diastolic volume. Patients with RVOTO showed
      significant higher RV circumferential strain (CS) (P = 0.02) and RV radial strain
      (RS) (P = 0.02) values, whereas RV longitudinal strain (LS) did not differ
      between the two groups (P = 0.39). The degree of RVOTO showed a significant
      correlation with RV-CS (r = 0.37; P = 0.006) and RV-RS (r = 0.30; P = 0.03) while
      RV-LS was unrelated to RVOTO (r = 0.06; P = 0.68). Significant relationships
      between RV and LV strain parameters were only found in the RVOTO group.
      Interventricular dyssynchrony was significantly higher in the group without RVOTO
      (P = 0.03) while LV-LS (P = 0.03) and LV intraventricular synchrony (P = 0.05)
      were impaired in the RVOTO group. CONCLUSIONS: In patients after TOF repair,
      residual RVOTO seems to preserve RV strain and results in stronger RV-LV
      interactions and less interventricular dyssynchrony and may therefore possess an
      early protective effect on RV remodelling. However, the potential negative impact
      of residual pulmonary stenosis on LV strain and intraventricular synchrony needs
      further investigation.

PMID- 25378365
TI  - Personal navigation increases colorectal cancer screening uptake.
AB  - BACKGROUND: Prior randomized, controlled trials (RCTs) indicate that patient
      navigation can boost colorectal cancer screening rates in primary care. The
      sparse literature on pragmatic trials of interventions designed to increase
      colorectal cancer screening adherence motivated this trial on the impact of a
      patient navigation intervention that included support for performance of the
      participants' preferred screening test (colonoscopy or stool blood testing).
      MATERIALS AND METHODS: Primary care patients (n = 5,240), 50 to 74 years of age,
      with no prior diagnosis of bowel cancer and no record of a recent colorectal
      cancer screening test, were identified at the Group Health Centre in northern
      Ontario. These patients were randomly assigned to an intervention group (n =
      2,629) or a usual care control group (n = 2,611). Intervention group participants
      were contacted by a trained nurse navigator by telephone to discuss colorectal
      cancer screening. Interested patients met with the navigator, who helped them
      identify and arrange for performance of the preferred screening test. Control
      group participants received usual care. Multivariate analyses were conducted
      using medical records data to assess intervention impact on screening adherence
      within 12 months after randomization. RESULTS: Mean patient age was 59 years, and
      50% of participants were women. Colorectal cancer screening adherence was higher
      in the intervention group (35%) than in the control group (20%), a difference
      that was statistically significant (OR, 2.11; confidence interval, 1.87-2.39).
      CONCLUSION: Preference-based patient navigation increased screening uptake in a
      pragmatic RCT. IMPACT: Patient navigation increased colorectal cancer screening
      rates in a pragmatic RCT in proportions similar to those observed in explanatory
      RCTs.

PMID- 25378366
TI  - Comparison of uptake of colorectal cancer screening based on fecal immunochemical
      testing (FIT) in males and females: a systematic review and meta-analysis.
AB  - BACKGROUND: Colorectal cancer is the third most common cancer in males and the
      second in females worldwide. Incidence and mortality are higher in men than
      women. Colorectal cancer screening is effective in reducing mortality.
      Internationally, fecal immunochemical testing (FIT) is increasingly being
      recommended as the primary screening test. This systematic review and meta
      analysis aimed to determine whether uptake of FIT screening differs between men
      than women. METHODS: We searched PubMed and Embase for peer-reviewed articles
      published in English during 2000-2013 for randomized controlled trials (RCT) or
      observational studies of screening using FIT that quantified numbers invited and
      participating by gender. Meta-analysis was performed using a random effects
      model. RESULTS: Six hundred and eighty-five citations were identified, 19 meeting
      the inclusion criteria. Random effects meta-analysis found male uptake was
      significantly lower than female uptake [odds ratio (OR), 0.84; 95% confidence
      interval (CI), 0.75-0.95; P < 0.01]. This generally persisted throughout subgroup
      analysis of study design (RCTs vs. observational studies and study quality),
      screening organization (methods of invitation, number of samples, age range of
      screening, recommendations, and reminders), and setting. CONCLUSIONS: Meta
      analysis of FIT screening studies indicates significantly lower uptake among men.
      IMPACT: Further investigation is required into factors influencing acceptability
      and participation of FIT screening in both sexes.

PMID- 25378367
TI  - Axe the L55 payment for dementia diagnosis, say doctors.

PMID- 25378369
TI  - Crowding by a single bar: probing pattern recognition mechanisms in the visual
      periphery.
AB  - Whereas visual crowding does not greatly affect the detection of the presence of
      simple visual features, it heavily inhibits combining them into recognizable
      objects. Still, crowding effects have rarely been directly related to general
      pattern recognition mechanisms. In this study, pattern recognition mechanisms in
      visual periphery were probed using a single crowding feature. Observers had to
      identify the orientation of a rotated T presented briefly in a peripheral
      location. Adjacent to the target, a single bar was presented. The bar was either
      horizontal or vertical and located in a random direction from the target. It
      appears that such a crowding bar has very strong and regular effects on the
      identification of the target orientation. The observer's responses are determined
      by approximate relative positions of basic visual features; exact image-based
      similarity to the target is not important. A version of the "standard model" of
      object recognition with second-order features explains the main regularities of
      the data. 

PMID- 25378370
TI  - Effect of light level on the reference frames of visual motion processing.
AB  - It is empirically known that some action-related visual tasks, which may rely on
      the construction of spatiotopic coordinates, are not well conducted under mesopic
      vision. The aim of this study was to clarify the effect of light level on the
      reference frame, such as retinotopic and spatiotopic coordinate bases, associated
      with visual motion processing. For this purpose, we used a phenomenon called
      visual motion priming in which the perceived direction of a directionally
      ambiguous test stimulus is influenced by the moving direction of a priming
      stimulus. Previous studies have shown that negative and positive motion priming
      are conspicuously observed in retinotopic and spatiotopic coordinates,
      respectively. In the experiments, participants made a saccade after the
      termination of the priming stimulus and judged the perceived direction of the
      test stimulus presented subsequently in retinotopic or spatiotopic coordinates at
      different light levels. We found that in retinotopic coordinates, negative motion
      priming was observed at all light levels. In spatiotopic coordinates, positive
      motion priming was observed at photopic and scotopic light levels, whereas the
      strength of motion priming was greatly reduced at mesopic light levels. These
      results were robust to the change in the luminance contrast or the saccadic eye
      movement per se. Different spatiotemporal properties of cones and rods at mesopic
      light levels may disturb the construction of a spatiotopic representation of
      motion, which leads to the disappearance of visual motion priming in spatiotopic
      coordinates during mesopic vision. 

PMID- 25378368
TI  - Auditory motion processing after early blindness.
AB  - Studies showing that occipital cortex responds to auditory and tactile stimuli
      after early blindness are often interpreted as demonstrating that early blind
      subjects "see" auditory and tactile stimuli. However, it is not clear whether
      these occipital responses directly mediate the perception of auditory/tactile
      stimuli, or simply modulate or augment responses within other sensory areas. We
      used fMRI pattern classification to categorize the perceived direction of motion
      for both coherent and ambiguous auditory motion stimuli. In sighted individuals,
      perceived motion direction was accurately categorized based on neural responses
      within the planum temporale (PT) and right lateral occipital cortex (LOC). Within
      early blind individuals, auditory motion decisions for both stimuli were
      successfully categorized from responses within the human middle temporal complex
      (hMT+), but not the PT or right LOC. These findings suggest that early blind
      responses within hMT+ are associated with the perception of auditory motion, and
      that these responses in hMT+ may usurp some of the functions of nondeprived PT.
      Thus, our results provide further evidence that blind individuals do indeed "see"
      auditory motion. 

PMID- 25378371
TI  - BMI is an important driver of beta-cell loss in type 1 diabetes upon diagnosis in
      10 to 18-year-old children.
AB  - OBJECTIVE: Body weight-related insulin resistance probably plays a role in
      progression to type 1 diabetes, but has an uncertain impact following diagnosis.
      In this study, we investigated whether BMI measured at diagnosis was an
      independent predictor of C-peptide decline 1-year post-diagnosis. DESIGN:
      Multicentre longitudinal study carried out at diagnosis and up to 1-year follow
      up. METHODS: Data on C-peptide were collected from seven diabetes centres in
      Europe. Patients were grouped according to age at diagnosis (<5 years, n=126; >5
      years <10 years, n=295; >10 years <18 years, n=421; >18 years, n=410). Linear
      regression was used to investigate whether BMI was an independent predictor of
      change in fasting C-peptide over 1 year. Models were additionally adjusted for
      baseline insulin dose and HbA1c. RESULTS: In individuals diagnosed between 0 and
      5 years, 5 and 10 years and those diagnosed >18 years, we found no association
      between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at
      baseline was associated with a greater decline in fasting C-peptide over 1 year
      with a decrease (beta 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m(2)
      higher baseline BMI (P=0.001). This association remained significant after
      adjusting for gender and differences in HbA1c and insulin dose (beta=0.026, 95%
      CI=0.0097, 0.042; P=0.002). CONCLUSIONS: These observations indicate that
      increased body weight and increased insulin demand are associated with more rapid
      disease progression after diagnosis of type 1 diabetes in an age group 10-18
      years. This should be considered in studies of beta-cell function in type 1
      diabetes.

PMID- 25378372
TI  - Determination of Aflatoxin M1 in Milk Powder by Ultrasonic-Assisted Extraction
      and Dispersive Solid-Phase Clean-up.
AB  - This work describes the application of ultrasound-assisted dispersive solid-phase
      extraction (UA-DSPE) as a sample preparation approach for aflatoxin M1 (AFM1) and
      also its subsequent determination by HPLC-fluorescence detection. A Box-Behnken
      design in combination with response surface methodology was implemented to
      determine the variables affecting the extraction procedure. The effects of
      different variables, including type and quantity of clean-up phase,
      ultrasonication time, ultrasonication temperature, nature and volume of the
      leaching solvent, were investigated in the optimization study. Primary secondary
      amine (PSA) and acetonitrile were selected as the clean-up phase and the leaching
      solvent, respectively. The obtained optimized values were 30 mg of PSA, 10 min
      ultrasonication time, 32 degrees C ultrasonication temperature and 10 mL of
      acetonitrile. Under the optimal conditions, the limit of detection and limit of
      quantification were 0.0012 and 0.0045 ug kg(-1), respectively. The recoveries of
      the UA-DSPE procedure ranged from 80 to 92%, with relative standard deviations
      lower than 10% in all cases. Eventually, this method was successfully applied to
      the extraction of AFM1 in milk powder samples. 

PMID- 25378373
TI  - Postoperative observation of children after endoscopic type 1 posterior laryngeal
      cleft repair.
AB  - OBJECTIVES: To report the perioperative management and surgical outcomes in a
      large series of pediatric patients with endoscopically repaired type 1 posterior
      laryngeal cleft (PLC). STUDY DESIGN: Case series with chart review. SETTING:
      Urban, tertiary care, free-standing pediatric hospital. SUBJECTS AND METHODS:
      Patients who underwent endoscopic carbon dioxide laser-assisted repair of type 1
      posterior laryngeal clefts between January 2006 and December 2012. Medical
      records were reviewed. RESULTS: Fifty-four patients (34 male) underwent repair of
      type 1 PLC. Median age was 25.5 months (range, 2-120 months). Indications for
      repair included aspiration (n = 39; 72%), chronic bronchitis (n = 13; 24%), and
      stridor with feeds (n = 2; 4%). No children remained intubated postoperatively.
      Thirty-three patients (61%) stayed in overnight observation ("Obs PLC") and 21
      patients (39%) stayed in the pediatric intensive care unit ("PICU PLC")
      postoperatively. Between Obs PLC and PICU PLC groups, there was no significant
      difference in age (mean 22 vs 30 months, respectively; P = .28). Comorbidities
      were similar between the groups. Symptoms improved in 41 of the 54 patients
      (76%). No postoperative complications were noted. Two patients required revision
      PLC repair. The cost of admitting a patient to a lower acuity location was
      estimated to be 60% less per day than cost of a PICU admission. CONCLUSIONS: The
      endoscopic surgical repair of a type 1 PLC is successful and has a low morbidity
      and complication rate. Patients may be safely managed in an observation unit and
      without postoperative intubation. This approach achieved a marked cost reduction
      in postoperative care.

PMID- 25378374
TI  - Association of serum bicarbonate with bone fractures in hemodialysis patients:
      the mineral and bone disorder outcomes study for Japanese CKD stage 5D patients
      (MBD-5D).
AB  - BACKGROUND/AIMS: Bone fracture is often complicated in hemodialysis (HD)
      patients. Metabolic acidosis is related to bone disease and muscle wasting, but
      it is not known whether acid-base disturbance is associated with the risk of bone
      fractures. The aim of this study was to clarify the association of serum
      bicarbonate level with bone fracture in HD patients. METHODS: Using a subcohort
      of the Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D
      Patients (MBD-5D), 890 prevalent HD patients (age: 62 years old, male: 62.8%,
      duration of dialysis: 8.3 years) with secondary hyperparathyroidism were studied.
      After measuring predialysis serum bicarbonate at a 2-day interdialytic interval,
      we prospectively followed them every 3 months, and examined the occurrence of any
      type of bone fracture or hospitalization due to fracture over a 3-year
      observation period. RESULTS: Seventy-four bone fractures and 47 hospitalizations
      due to fracture were observed during the follow-up period. HD patients with serum
      bicarbonate <20 mmol/l had a 1.93 (95% CI 1.01-3.71)-fold higher risk for all
      cause fractures than those with serum bicarbonate of 20.0-21.9 mmol/l. A higher
      bicarbonate level (>=22 mmol/l) was also related to an increased risk of bone
      fracture. A restricted cubic regression spline disclosed that the higher or the
      lower than 21.0 mmol/l of serum bicarbonate, the greater the risk for bone
      fracture. CONCLUSION: Both a lower level and a higher level of predialysis
      bicarbonate concentration were associated with risk of bone fracture in HD
      patients with secondary hyperparathyroidism.

PMID- 25378375
TI  - Ophiopogonin D attenuates doxorubicin-induced autophagic cell death by relieving
      mitochondrial damage in vitro and in vivo.
AB  - It has been reported that ophiopogonin D (OP-D), a steroidal glycoside and an
      active component extracted from Ophiopogon japonicas, promotes antioxidative
      protection of the cardiovascular system. However, it is unknown whether OP-D
      exerts protective effects against doxorubicin (DOX)-induced autophagic
      cardiomyocyte injury. Here, we demonstrate that DOX induced excessive autophagy
      through the generation of reactive oxygen species (ROS) in H9c2 cells and in
      mouse hearts, which was indicated by a significant increase in the number of
      autophagic vacuoles, LC3-II/LC3-I ratio, and upregulation of the expression of
      GFP-LC3. Pretreatment with OP-D partially attenuated the above phenomena, similar
      to the effects of treatment with 3-methyladenine. In addition, OP-D treatment
      significantly relieved the disruption of the mitochondrial membrane potential by
      antioxidative effects through downregulating the expression of both
      phosphorylated c-Jun N-terminal kinase and extracellular signal-regulated kinase.
      The ability of OP-D to reduce the generation of ROS due to mitochondrial damage
      and, consequently, to inhibit autophagic activity partially accounts for its
      protective effects in the hearts against DOX-induced toxicity. 

PMID- 25378376
TI  - Efficacy of oral hydration in the prevention of contrast-induced acute kidney
      injury in patients undergoing coronary angiography or intervention.
AB  - BACKGROUND: Efficacy of intravenous (IV) volume expansion in preventing contrast
      induced acute kidney injury (CI-AKI) is well known. However, the role of oral
      hydration has not been well established. The aim of this work was to evaluate the
      efficacy of oral hydration in preventing CI-AKI. METHODS: We prospectively
      randomized 225 patients undergoing coronary angiography and/or percutaneous
      coronary intervention in either oral hydration or IV hydration groups. Patients
      who have at least one of the high-risk factors for developing CI-AKI (advanced
      age, type 2 diabetes mellitus, anemia, hyperuricemia, a history of cardiac
      failure or systolic dysfunction) were included in the study. All patients had
      normal renal function or stage 1-2 chronic kidney disease. Patients in the oral
      hydration group were encouraged to drink unrestricted amounts of fluids freely
      whereas isotonic saline infusion was performed by the standard protocol in the IV
      hydration group. RESULTS: CI-AKI occurred in 8/116 patients (6.9%) in the oral
      hydration group and 8/109 patients (7.3%) in the IV hydration group (p = 0.89).
      There was also no statistically significant difference between the two groups
      when different CI-AKI definitions were taken into account. CONCLUSION: Oral
      hydration is as effective as IV hydration in preventing CI-AKI in patients with
      normal kidney function or stage 1-2 chronic kidney disease, and who also have at
      least one of the other high-risk factors for developing CI-AKI.

PMID- 25378377
TI  - Disparities in the quality of primary healthcare for socially deprived children.

PMID- 25378378
TI  - Active management of food allergy: an emerging concept.
AB  - IgE-mediated food allergies are common and currently there is no cure.
      Traditionally, management has relied upon patient education, food avoidance and
      the provision of an emergency medication plan. Despite this, food allergy can
      significantly impact on quality of life. Therefore, in recent years, evolving
      research has explored alternative management strategies. A more active approach
      to management is being adopted, which includes early introduction of potentially
      allergenic foods, anticipatory testing, active monitoring, desensitisation to
      food allergens and active risk management. This review will discuss these areas
      in turn. 

PMID- 25378379
TI  - Current primary care management of children aged 1-36 months with urinary tract
      infections in Europe: large scale survey of paediatric practice.
AB  - OBJECTIVE: To describe current practice among European paediatricians regarding
      diagnosis and management of urinary tract infections in children aged 1-36 months
      and to compare these practices with recently published guidelines. DESIGN: Web
      based large scale survey evaluating knowledge of, attitudes towards and the
      methods for diagnosing, treating and managing urinary tract infections in
      children. SETTING: Primary and secondary care practices in Europe. SAMPLE: 1129
      paediatricians. RESULTS: A diagnosis of urinary tract infection is considered by
      62% of the respondents in children aged 1-36 months with unexplained fever. The
      preferred method of urine collection is use of a bag (53% for infants <3 months
      and 59% for children 4-36 months of age). 60% of paediatricians agree that oral
      and parenteral antibiotics have equal efficacy. Co-amoxiclav is the antibiotic of
      choice for 41% of participants, while 9% prescribe amoxicillin. 80% of
      respondents prescribe ultrasound in all children with a confirmed urinary tract
      infection. 63% of respondents prescribe a cystography when abnormalities are
      revealed during ultrasound evaluation. A quarter of respondents recommend
      antibiotic prophylaxis for all children with any vesicoureteral reflux. The data
      among European countries are very heterogeneous. The three most recent urinary
      tract infection guidelines (the National Institute for Health and Care Excellence
      (NICE), the American Academy of Paediatrics and the Italian Society of Paediatric
      Nephrology) are not followed properly. CONCLUSIONS: Management of febrile urinary
      tract infections remains controversial and heterogeneous in Europe. Simple,
      short, practical and easy-to-remember guidelines and educational strategies to
      ensure their implementation should be developed.

PMID- 25378380
TI  - Mechanical design, analysis, and laboratory testing of a dental implant with
      axial flexibility similar to natural tooth with periodontal ligament.
AB  - At the interface between the jawbone and the roots of natural teeth, a thin,
      elastic, shock-absorbing tissue, called the periodontal ligament, forms a cushion
      which provides certain flexibility under mechanical loading. The dental
      restorations supported by implants, however, involve comparatively rigid
      connections to the jawbone. This causes overloading of the implant while bearing
      functional loading together with neighboring natural teeth, which leads to high
      stresses within the implant system and in the jawbone. A dental implant, with
      resilient components in the upper structure (abutment) in order to mimic the
      mechanical behavior of the periodontal ligament in the axial direction, was
      designed, analyzed in silico, and produced for mechanical testing. The aims of
      the design were avoiding high levels of stress, loosening of the abutment
      connection screw, and soft tissue irritations. The finite element analysis of the
      designed implant revealed that the elastic abutment yielded a similar axial
      mobility with the natural tooth while keeping stress in the implant at safe
      levels. The in vitro mechanical testing of the prototype resulted in similar
      axial mobility predicted by the analysis and as that of a typical natural tooth.
      The abutment screw did not loosen under repeated loading and there was no static
      or fatigue failure. 

PMID- 25378381
TI  - Social dysfunctioning and brain in borderline personality disorder.
AB  - Interpersonal dysfunction is the most prominent and best discriminating
      characteristic in individuals with borderline personality disorder (BPD). Data
      from experimental psychopathology point to emotional lability, (auto-)aggression,
      threat hypersensitivity, poor chance of interpersonal repair, frequent
      misunderstandings and self/other diffusion as the most significant factors which
      contribute to the interpersonal derailments typical of BPD. Neuroscientific
      methods are suitable to elucidate the mechanisms which mediate deficient social
      functioning in BPD, i.e. affective dysregulation, impulsivity/disinhibition and
      poor social cognition as well as their neurobiological correlates. Low
      prefrontoamygdalar coupling together with low activity in inhibiting prefrontal
      areas, high activity in the mirror neuron system, low activity in the mentalizing
      circuit, and low anterior insular activity in case of social norm violations are
      the most significant functional neuroimaging findings that have been reported
      from individuals with BPD, up to now. In addition, peculiarities of facial
      emotion processing have been detected by means of psychophysiological methodology
      in BPD patients. Data have led to preliminary models of social dysfunctioning in
      BPD that have to be experimentally tested in the future, evolving neuroscience
      into an important tool to better understand what distresses patients with BPD
      when communicating with others.

PMID- 25378382
TI  - The effects of smokeless cookstoves on peak expiratory flow rates in rural
      Honduras.
AB  - BACKGROUND: The use of biomass fuel for cooking in traditional cookstove designs
      negatively affects respiratory health of communities in developing countries.
      Indoor pollution affects particularly women and children, who are participating
      in food preparation. The effects of smokeless cookstove designs on indoor
      pollution are well documented, but few studies exist to assess the effects of
      improved stove designs on the respiratory health of community members. METHODS:
      This study uses peak expiratory flow rate (PEFR) measurements in a before-and
      after format to assess respiratory function of inhabitants of all 30 houses of
      Buenas Noches in central Honduras. PEFRs are measured before and 6 months after
      the installation of Justa stoves in people's homes. Health behaviors, respiratory
      symptoms and fire wood use are evaluated in a door-to-door survey format.
      RESULTS: A total of 137 eligible women and children between 6 and 14 years
      participated in the study. PEFR improved by 9.9-18.5% (P < 0.001) depending on
      the participants' exposure to indoor pollution. Health complaints like cough and
      behaviors like clinic visits did not change with the introduction of smokeless
      cookstove technology. CONCLUSIONS: Smokeless stoves improve respiratory health in
      an environment of high levels of indoor pollution.

PMID- 25378383
TI  - Low pressure headaches caused by spontaneous intracranial hypotension.

PMID- 25378385
TI  - Safety of modern treatment for cervical pre-cancer.

PMID- 25378384
TI  - Risk of preterm delivery with increasing depth of excision for cervical
      intraepithelial neoplasia in England: nested case-control study.
AB  - OBJECTIVE: To determine the association between depth of excision of cervical
      intraepithelial neoplasia and risk of preterm birth. DESIGN: Case-control study
      nested in record linkage cohort study. SETTING: 12 hospitals in England.
      PARTICIPANTS: From a cohort of 11 471 women with at least one histological sample
      taken at colposcopy and a live singleton birth (before or after colposcopy), 1313
      women with a preterm birth (20-36 weeks) were identified and frequency matched on
      maternal age at delivery, parity, and study site to 1313 women with term births
      (38-42 weeks). MAIN OUTCOME MEASURES: Risk of preterm birth and very/extreme
      preterm birth by depth of excisional treatment of the cervical transformation
      zone. RESULTS: After exclusions, 768 preterm births (cases) and 830 term births
      after colposcopy remained. The risk of preterm birth was no greater in women with
      a previous small (<10 mm) excision (absolute risk 7.5%, 95% confidence interval
      6.0% to 8.9%) than in women with a diagnostic punch biopsy (7.2%, 5.9% to 8.5%).
      Women with a medium (10-14 mm) (absolute risk 9.6%; relative risk 1.28, 0.98 to
      1.68), large (15-19 mm) (15.3%; 2.04, 1.41 to 2.96), or very large (>= 20 mm)
      excision (18.0%; 2.40, 1.53 to 3.75) had a higher risk of preterm delivery than
      those with small excision. The same pattern was seen in 161 women with
      very/extremely preterm births (20-31 weeks) and with increasing volume excised.
      Most births were conceived more than three years after colposcopy, and the risk
      of preterm delivery did not seem to depend on time from excision to conception.
      CONCLUSIONS: The risk of preterm birth is at most minimally affected by a small
      excision. Larger excisions, particularly over 15 mm or 2.66 cm(3), are associated
      with a doubling of the risk of both preterm and very preterm births. The risk
      does not decrease with increasing time from excision to conception. Efforts
      should be made to excise the entire lesion while preserving as much healthy
      cervical tissue as possible. Close obstetric monitoring is warranted for women
      who have large excisions of the cervical transformation zone.

PMID- 25378387
TI  - Chrysanthemyl diphosphate synthase operates in planta as a bifunctional enzyme
      with chrysanthemol synthase activity.
AB  - Chrysanthemyl diphosphate synthase (CDS) is the first pathway-specific enzyme in
      the biosynthesis of pyrethrins, the most widely used plant-derived pesticide. CDS
      catalyzes c1'-2-3 cyclopropanation reactions of two molecules of dimethylallyl
      diphosphate (DMAPP) to yield chrysanthemyl diphosphate (CPP). Three proteins are
      known to catalyze this cyclopropanation reaction of terpene precursors. Two of
      them, phytoene and squalene synthase, are bifunctional enzymes with both
      prenyltransferase and terpene synthase activity. CDS, the other member, has been
      reported to perform only the prenyltransferase step. Here we show that the NDXXD
      catalytic motif of CDS, under the lower substrate conditions prevalent in plants,
      also catalyzes the next step, converting CPP into chrysanthemol by hydrolyzing
      the diphosphate moiety. The enzymatic hydrolysis reaction followed conventional
      Michaelis-Menten kinetics, with a Km value for CPP of 196 MUm. For the
      chrysanthemol synthase activity, DMAPP competed with CPP as substrate. The DMAPP
      concentration required for half-maximal activity to produce chrysanthemol was
      ~100 MUm, and significant substrate inhibition was observed at elevated DMAPP
      concentrations. The N-terminal peptide of CDS was identified as a plastid
      targeting peptide. Transgenic tobacco plants overexpressing CDS emitted
      chrysanthemol at a rate of 0.12-0.16 MUg h(-1) g(-1) fresh weight. We propose
      that CDS should be renamed a chrysanthemol synthase utilizing DMAPP as substrate.

PMID- 25378388
TI  - Scaffold protein X11alpha interacts with kalirin-7 in dendrites and recruits it
      to Golgi outposts.
AB  - Pyramidal neurons in the mammalian forebrain receive their synaptic inputs
      through their dendritic trees, and dendritic spines are the sites of most
      excitatory synapses. Dendritic spine structure is important for brain development
      and plasticity. Kalirin-7 is a guanine nucleotide-exchange factor for the small
      GTPase Rac1 and is a critical regulator of dendritic spine remodeling. The
      subcellular localization of kalirin-7 is thought to be important for regulating
      its function in neurons. A yeast two-hybrid screen has identified the adaptor
      protein X11alpha as an interacting partner of kalirin-7. Here, we show that
      kalirin-7 and X11alpha form a complex in the brain, and this interaction is
      mediated by the C terminus of kalirin-7. Kalirin-7 and X11alpha co-localize at
      excitatory synapses in cultured cortical neurons. Using time-lapse imaging of
      fluorescence recovery after photobleaching, we show that X11alpha is present in a
      mobile fraction of the postsynaptic density. X11alpha also localizes to Golgi
      outposts in dendrites, and its overexpression induces the removal of kalirin-7
      from spines and accumulation of kalirin-7 in Golgi outposts. In addition, neurons
      overexpressing X11alpha displayed thinner spines. These data support a novel
      mechanism of regulation of kalirin-7 localization and function in dendrites,
      providing insight into signaling pathways underlying neuronal plasticity.
      Dissecting the molecular mechanisms of synaptic structural plasticity will
      improve our understanding of neuropsychiatric and neurodegenerative disorders, as
      kalirin-7 has been associated with schizophrenia and Alzheimer disease. 

PMID- 25378389
TI  - Nitroxyl (HNO) reacts with molecular oxygen and forms peroxynitrite at
      physiological pH. Biological Implications.
AB  - Nitroxyl (HNO), the protonated one-electron reduction product of NO, remains an
      enigmatic reactive nitrogen species. Its chemical reactivity and biological
      activity are still not completely understood. HNO donors show biological effects
      different from NO donors. Although HNO reactivity with molecular oxygen is
      described in the literature, the product of this reaction has not yet been
      unambiguously identified. Here we report that the decomposition of HNO donors
      under aerobic conditions in aqueous solutions at physiological pH leads to the
      formation of peroxynitrite (ONOO(-)) as a major intermediate. We have
      specifically detected and quantified ONOO(-) with the aid of boronate probes,
      e.g. coumarin-7-boronic acid or 4-boronobenzyl derivative of fluorescein methyl
      ester. In addition to the major phenolic products, peroxynitrite-specific minor
      products of oxidation of boronate probes were detected under these conditions.
      Using the competition kinetics method and a set of HNO scavengers, the value of
      the second order rate constant of the HNO reaction with oxygen (k = 1.8 * 10(4)
      m(-1) s(-1)) was determined. The rate constant (k = 2 * 10(4) m(-1) s(-1)) was
      also determined using kinetic simulations. The kinetic parameters of the
      reactions of HNO with selected thiols, including cysteine, dithiothreitol, N
      acetylcysteine, captopril, bovine and human serum albumins, and hydrogen sulfide,
      are reported. Biological and cardiovascular implications of nitroxyl reactions
      are discussed. 

PMID- 25378390
TI  - Allosteric inhibition of the neuropeptidase neurolysin.
AB  - Neuropeptidases specialize in the hydrolysis of the small bioactive peptides that
      play a variety of signaling roles in the nervous and endocrine systems. One
      neuropeptidase, neurolysin, helps control the levels of the dopaminergic circuit
      modulator neurotensin and is a member of a fold group that includes the
      antihypertensive target angiotensin converting enzyme. We report the discovery of
      a potent inhibitor that, unexpectedly, binds away from the enzyme catalytic site.
      The location of the bound inhibitor suggests it disrupts activity by preventing a
      hinge-like motion associated with substrate binding and catalysis. In support of
      this model, the inhibition kinetics are mixed, with both noncompetitive and
      competitive components, and fluorescence polarization shows directly that the
      inhibitor reverses a substrate-associated conformational change. This new type of
      inhibition may have widespread utility in targeting neuropeptidases. 

PMID- 25378391
TI  - Modulation of the mevalonate pathway by akt regulates macrophage survival and
      development of pulmonary fibrosis.
AB  - Protein kinase B (Akt) is a key effector of multiple cellular processes,
      including cell survival. Akt, a serine/threonine kinase, is known to increase
      cell survival by regulation of the intrinsic pathway for apoptosis. In this
      study, we found that Akt modulated the mevalonate pathway, which is also linked
      to cell survival, by increasing Rho GTPase activation. Akt modulated the pathway
      by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser(96). This
      phosphorylation in macrophages increased activation of Rac1, which enhanced
      macrophage survival because mutation of MDD (MDDS96A) induced apoptosis. Akt
      mediated activation in macrophages was specific for Rac1 because Akt did not
      increase activity of other Rho GTP-binding proteins. The relationship between Akt
      and Rac1 was biologically relevant because Akt(+/-) mice had significantly less
      active Rac1 in alveolar macrophages, and macrophages from Akt(+/-) mice had an
      increase in active caspase-9 and -3. More importantly, Akt(+/-) mice were
      significantly protected from the development of pulmonary fibrosis, suggesting
      that macrophage survival is associated with the fibrotic phenotype. These
      observations for the first time suggest that Akt plays a critical role in the
      development and progression of pulmonary fibrosis by enhancing macrophage
      survival via modulation of the mevalonate pathway. 

PMID- 25378392
TI  - Post-translational regulation of the type III inositol 1,4,5-trisphosphate
      receptor by miRNA-506.
AB  - The type III isoform of the inositol 1,4,5-trisphosphate receptor (InsP3R3) is
      apically localized and triggers Ca(2+) waves and secretion in a number of
      polarized epithelia. However, nothing is known about epigenetic regulation of
      this InsP3R isoform. We investigated miRNA regulation of InsP3R3 in primary bile
      duct epithelia (cholangiocytes) and in the H69 cholangiocyte cell line, because
      the role of InsP3R3 in cholangiocyte Ca(2+) signaling and secretion is well
      established and because loss of InsP3R3 from cholangiocytes is responsible for
      the impairment in bile secretion that occurs in a number of liver diseases.
      Analysis of the 3'-UTR of human InsP3R3 mRNA revealed two highly conserved
      binding sites for miR-506. Transfection of miR-506 mimics into cell lines
      expressing InsP3R3-3'UTR-luciferase led to decreased reporter activity, whereas
      co-transfection with miR-506 inhibitors led to enhanced activity. Reporter
      activity was abrogated in isolated mutant proximal or distal miR-506 constructs
      in miR-506-transfected HEK293 cells. InsP3R3 protein levels were decreased by miR
      506 mimics and increased by inhibitors, and InsP3R3 expression was markedly
      decreased in H69 cells stably transfected with miR-506 relative to control cells.
      miR-506-H69 cells exhibited a fibrotic signature. In situ hybridization revealed
      elevated miR-506 expression in vivo in human-diseased cholangiocytes. Histamine
      induced, InsP3-mediated Ca(2+) signals were decreased by 50% in stable miR-506
      cells compared with controls. Finally, InsP3R3-mediated fluid secretion was
      significantly decreased in isolated bile duct units transfected with miR-506,
      relative to control IBDU. Together, these data identify miR-506 as a regulator of
      InsP3R3 expression and InsP3R3-mediated Ca(2+) signaling and secretion. 

PMID- 25378393
TI  - Tumor progression locus 2-dependent oxidative burst drives phosphorylation of
      extracellular signal-regulated kinase during TLR3 and 9 signaling.
AB  - Signal transduction via NFkappaB and MAP kinase cascades is a universal response
      initiated upon pathogen recognition by Toll-like receptors (TLRs). How activation
      of these divergent signaling pathways is integrated to dictate distinct immune
      responses to diverse pathogens is still incompletely understood. Herein, contrary
      to current perception, we demonstrate that a signaling pathway defined by the
      inhibitor of kappaB kinase beta (IKKbeta), MAP3 kinase tumor progression locus 2
      (Tpl2/MAP3K8), and MAP kinase ERK is differentially activated by TLRs. TLRs 2, 4,
      and 7 directly activate this inflammatory axis, inducing immediate ERK
      phosphorylation and early TNFalpha secretion. In addition to TLR adaptor
      proteins, IKKbeta-Tpl2-ERK activation by TLR4 is regulated by the TLR4 co
      receptor CD14 and the tyrosine kinase Syk. Signals from TLRs 3 and 9 do not
      initiate early activation of IKKbeta-Tpl2-ERK pathway but instead induce delayed,
      NADPH-oxidase-dependent ERK phosphorylation and TNFalpha secretion via autocrine
      reactive oxygen species signaling. Unexpectedly, Tpl2 is an essential regulator
      of ROS production during TLR signaling. Overall, our study reveals distinct
      mechanisms activating a common inflammatory signaling cascade and delineates
      differences in MyD88-dependent signaling between endosomal TLRs 7 and 9. These
      findings further confirm the importance of Tpl2 in innate host defense mechanisms
      and also enhance our understanding of how the immune system tailors pathogen
      specific gene expression patterns. 

PMID- 25378394
TI  - Tumor necrosis factor receptor 2 (TNFR2).interleukin-17 receptor D (IL-17RD)
      heteromerization reveals a novel mechanism for NF-kappaB activation.
AB  - TNF receptor 2 (TNFR2) exerts diverse roles in the pathogenesis of inflammatory
      and autoimmune diseases. Here, we report that TNFR2 but not TNFR1 forms a
      heteromer with interleukin-17 receptor D (IL-17RD), also named Sef, to activate
      NF-kappaB signaling. TNFR2 associates with IL-17RD, leading to mutual receptor
      aggregation and TRAF2 recruitment, which further activate the downstream cascade
      of NF-kappaB signaling. Depletion of IL-17RD impaired TNFR2-mediated activation
      of NF-kappaB signaling. Importantly, IL-17RD was markedly increased in renal
      tubular epithelial cells in nephritis rats, and a strong interaction of TNFR2 and
      IL-17RD was observed in the renal epithelia. The IL-17RD.TNFR2 complex in
      activation of NF-kappaB may explain the role of TNFR2 in inflammatory diseases
      including nephritis. 

PMID- 25378395
TI  - beta2-microglobulin amyloid fibrils are nanoparticles that disrupt lysosomal
      membrane protein trafficking and inhibit protein degradation by lysosomes.
AB  - Fragmentation of amyloid fibrils produces fibrils that are reduced in length but
      have an otherwise unchanged molecular architecture. The resultant nanoscale
      fibril particles inhibit the cellular reduction of the tetrazolium dye 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), a substrate commonly
      used to measure cell viability, to a greater extent than unfragmented fibrils.
      Here we show that the internalization of beta2-microglobulin (beta2m) amyloid
      fibrils is dependent on fibril length, with fragmented fibrils being more
      efficiently internalized by cells. Correspondingly, inhibiting the
      internalization of fragmented beta2m fibrils rescued cellular MTT reduction.
      Incubation of cells with fragmented beta2m fibrils did not, however, cause cell
      death. Instead, fragmented beta2m fibrils accumulate in lysosomes, alter the
      trafficking of lysosomal membrane proteins, and inhibit the degradation of a
      model protein substrate by lysosomes. These findings suggest that nanoscale
      fibrils formed early during amyloid assembly reactions or by the fragmentation of
      longer fibrils could play a role in amyloid disease by disrupting protein
      degradation by lysosomes and trafficking in the endolysosomal pathway. 

PMID- 25378396
TI  - Klotho up-regulates renal calcium channel transient receptor potential vanilloid
      5 (TRPV5) by intra- and extracellular N-glycosylation-dependent mechanisms.
AB  - The anti-aging protein Klotho is a type 1 membrane protein produced predominantly
      in the distal convoluted tubule. The ectodomain of Klotho is cleaved and secreted
      into the urine to regulate several ion channels and transporters. Secreted Klotho
      (sKL) up-regulates the TRPV5 calcium channel from the cell exterior by removing
      sialic acids from N-glycan of the channel and inhibiting its endocytosis. Because
      TRPV5 and Klotho coexpress in the distal convoluted tubule, we investigated
      whether Klotho regulates TRPV5 action from inside the cell. Whole-cell TRPV5
      mediated channel activity was recorded in HEK cells coexpressing TRPV5 and sKL or
      membranous Klotho (mKL). Transfection of sKL, but not mKL, produced detectable
      Klotho protein in cell culture media. As for sKL, mKL increased TRPV5 current
      density. The role of sialidase activity of mKL acting inside is supported by
      findings that mutations of putative sialidase activity sites in sKL and mKL
      abrogated the regulation of TRPV5 but that the extracellular application of a
      sialidase inhibitor prevented the regulation of TRPV5 by sKL only.
      Mechanistically, coexpression with a dominant-negative dynamin II prevented the
      regulation of TRPV5 by sKL but not by mKL. In contrast, blocking forward
      trafficking by brefeldin A prevented the effect with mKL but not with sKL.
      Therefore, Klotho up-regulates TRPV5 from both the inside and outside of cells.
      The intracellular action of Klotho is likely due to enhanced forward trafficking
      of channel proteins, whereas the extracellular action is due to inhibition of
      endocytosis. Both effects involve putative Klotho sialidase activity. These
      effects of Klotho may play important roles regarding calcium reabsorption in the
      kidney. 

PMID- 25378397
TI  - O-fucose monosaccharide of Drosophila Notch has a temperature-sensitive function
      and cooperates with O-glucose glycan in Notch transport and Notch signaling
      activation.
AB  - Notch (N) is a transmembrane receptor that mediates the cell-cell interactions
      necessary for many cell fate decisions. N has many epidermal growth factor-like
      repeats that are O-fucosylated by the protein O-fucosyltransferase 1 (O-Fut1),
      and the O-fut1 gene is essential for N signaling. However, the role of the
      monosaccharide O-fucose on N is unclear, because O-Fut1 also appears to have O
      fucosyltransferase activity-independent functions, including as an N-specific
      chaperon. Such an enzymatic activity-independent function could account for the
      essential role of O-fut1 in N signaling. To evaluate the role of the
      monosaccharide O-fucose modification in N signaling, here we generated a knock-in
      mutant of O-fut1 (O-fut1(R245A knock-in)), which expresses a mutant protein that
      lacks O-fucosyltransferase activity but maintains the N-specific chaperon
      activity. Using O-fut1(R245A knock-in) and other gene mutations that abolish the
      O-fucosylation of N, we found that the monosaccharide O-fucose modification of N
      has a temperature-sensitive function that is essential for N signaling. The O
      fucose monosaccharide and O-glucose glycan modification, catalyzed by Rumi,
      function redundantly in the activation of N signaling. We also showed that the
      redundant function of these two modifications is responsible for the presence of
      N at the cell surface. Our findings elucidate how different forms of
      glycosylation on a protein can influence the protein's functions. 

PMID- 25378398
TI  - Zymogen activation and subcellular activity of subtilisin kexin isozyme 1/site 1
      protease.
AB  - The proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease
      (S1P) plays crucial roles in cellular homeostatic functions and is hijacked by
      pathogenic viruses for the processing of their envelope glycoproteins. Zymogen
      activation of SKI-1/S1P involves sequential autocatalytic processing of its N
      terminal prodomain at sites B'/B followed by the herein newly identified C'/C
      sites. We found that SKI-1/S1P autoprocessing results in intermediates whose
      catalytic domain remains associated with prodomain fragments of different
      lengths. In contrast to other zymogen proprotein convertases, all incompletely
      matured intermediates of SKI-1/S1P showed full catalytic activity toward cellular
      substrates, whereas optimal cleavage of viral glycoproteins depended on B'/B
      processing. Incompletely matured forms of SKI-1/S1P further process cellular and
      viral substrates in distinct subcellular compartments. Using a cell-based sensor
      for SKI-1/S1P activity, we found that 9 amino acid residues at the cleavage site
      (P1-P8) and P1' are necessary and sufficient to define the subcellular location
      of processing and to determine to what extent processing of a substrate depends
      on SKI-1/S1P maturation. In sum, our study reveals novel and unexpected features
      of SKI-1/S1P zymogen activation and subcellular specificity of activity toward
      cellular and pathogen-derived substrates. 

PMID- 25378399
TI  - Human memory, but not naive, CD4+ T cells expressing transcription factor T-bet
      might drive rapid cytokine production.
AB  - We found that after stimulation for a few hours, memory but not naive CD4(+) T
      cells produced a large amount of IFN-gamma; however, the mechanism of rapid
      response of memory CD4(+) T cells remains undefined. We compared the expression
      of transcription factors in resting or activated naive and memory CD4(+) T cells
      and found that T-bet, but not pSTAT-1 or pSTAT-4, was highly expressed in resting
      memory CD4(+) T cells and that phenotypic characteristics of T-bet(+)CD4(+) T
      cells were CD45RA(low)CD62L(low) CCR7(low). After short-term stimulation,
      purified memory CD4(+) T cells rapidly produced effector cytokines that were
      closely associated with the pre-existence of T-bet. By contrast, resting naive
      CD4(+) T cells did not express T-bet, and they produced cytokines only after
      sustained stimulation. Our further studies indicated that T-bet was expressed in
      the nuclei of resting memory CD4(+) T cells, which might have important
      implications for rapid IFN-gamma production. Our results indicate that the pre
      existence and nuclear mobilization of T-bet in resting memory CD4(+) T cells
      might be a possible transcriptional mechanism for rapid production of cytokines
      by human memory CD4(+) T cells. 

PMID- 25378400
TI  - Aha1 can act as an autonomous chaperone to prevent aggregation of stressed
      proteins.
AB  - Aha1 (activator of Hsp90 ATPase) stimulates the ATPase activity of the molecular
      chaperone Hsp90 to accelerate the conformational cycle during which client
      proteins attain their final shape. Thereby, Aha1 promotes effective folding of
      Hsp90-dependent clients such as steroid receptors and many kinases involved in
      cellular signaling. In our current study, we find that Aha1 plays a novel,
      additional role beyond regulating the Hsp90 ATP hydrolysis rate. We propose a new
      concept suggesting that Aha1 acts as an autonomous chaperone and associates with
      stress-denatured proteins to prevent them from aggregation similar to the
      chaperonin GroEL. Our study reveals that an N-terminal sequence of 22 amino
      acids, present in human but absent from yeast Aha1, is critical for this
      capability. However, in lieu of fostering their refolding, Aha1 allows
      ubiquitination of bound clients by the E3 ubiquitin ligase CHIP. Accordingly,
      Aha1 may promote disposal of folding defective proteins by the cellular protein
      quality control. 

PMID- 25378401
TI  - NGX6a is degraded through a proteasome-dependent pathway without ubiquitination
      mediated by ezrin, a cytoskeleton-membrane linker.
AB  - Our previous study demonstrated that the NGX6b gene acts as a suppressor in the
      invasion and migration of nasopharyngeal carcinoma (NPC). Recently, we identified
      the novel isoform NGX6a, which is longer than NGX6b. In this study, we first
      found that NGX6a was degraded in NPC cells and that this degradation was mediated
      by ezrin, a linker between membrane proteins and the cytoskeleton. Specific
      siRNAs against ezrin increase the protein level of NGX6a in these cells. During
      degradation, NGX6a is not ubiquitinated but is degraded through a proteasome
      dependent pathway. The distribution pattern of ezrin was negatively associated
      with NGX6a in an immunochemistry analysis of a nasopharyngeal carcinoma tissue
      microarray and fetus multiple organ tissues and Western blot analysis in
      nasopharyngeal and NPC cell lines, suggesting that ezrin and NGX6a are associated
      and are involved in the progression and invasion of NPC. By mapping the
      interacting binding sites, the seven-transmembrane domain of NGX6a was found to
      be the critical region for the degradation of NGX6a, and the amino terminus of
      ezrin is required for the induction of NGX6a degradation. The knockdown of ezrin
      or transfection of the NGX6a mutant CO, which has an EGF-like domain and a
      transmembrane 1 domain, resulted in no degradation, significantly reducing the
      ability of invasion and migration of NPC cells. This study provides a novel
      molecular mechanism for the low expression of NGX6a in NPC cells and an important
      molecular event in the process of invasion and metastasis of nasopharyngeal
      carcinoma cells. 

PMID- 25378402
TI  - The prophage-encoded hyaluronate lyase has broad substrate specificity and is
      regulated by the N-terminal domain.
AB  - Streptococcus equi is the causative agent of the highly contagious disease
      "strangles" in equines and zoonotic meningitis in human. Spreading of infection
      in host tissues is thought to be facilitated by the bacterial gene encoded
      extracellular hyaluronate lyase (HL), which degrades hyaluronan (HA), chondroitin
      6-sulfate, and dermatan sulfate of the extracellular matrix). The clinical strain
      S. equi 4047 however, lacks a functional extracellular HL. The prophages of S.
      equi and other streptococci encode intracellular HLs which are reported to
      partially degrade HA and do not cleave any other glycosaminoglycans. The phage
      HLs are thus thought to play a role limited to the penetration of streptococcal
      HA capsules, facilitating bacterial lysogenization and not in the bacterial
      pathogenesis. Here we systematically looked into the structure-function
      relationship of S. equi 4047 phage HL. Although HA is the preferred substrate,
      this HL has weak activity toward chondroitin 6-sulfate and dermatan sulfate and
      can completely degrade all of them. Even though the catalytic triple-stranded
      beta-helix domain of phage HL is functionally independent, its catalytic
      efficiency and specificity is influenced by the N-terminal domain. The phage HL
      also interacts with human transmembrane glycoprotein CD44. The above results
      suggest that the streptococci can use phage HLs to degrade glycosaminoglycans of
      the extracellular matrix for spreading virulence factors and toxins while
      utilizing the disaccharides as a nutrient source for proliferation at the site of
      infection. 

PMID- 25378403
TI  - Metabolic control of Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      mediated caspase-2 suppression by the B55beta/protein phosphatase 2A (PP2A).
AB  - High levels of metabolic activity confer resistance to apoptosis. Caspase-2, an
      apoptotic initiator, can be suppressed by high levels of nutrient flux through
      the pentose phosphate pathway. This metabolic control is exerted via inhibitory
      phosphorylation of the caspase-2 prodomain by activated Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII). We show here that this activation of CaMKII
      depends, in part, on dephosphorylation of CaMKII at novel sites
      (Thr(393)/Ser(395)) and that this is mediated by metabolic activation of protein
      phosphatase 2A in complex with the B55beta targeting subunit. This represents a
      novel locus of CaMKII control and also provides a mechanism contributing to
      metabolic control of apoptosis. These findings may have implications for
      metabolic control of the many CaMKII-controlled and protein phosphatase 2A
      regulated physiological processes, because both enzymes appear to be responsive
      to alterations in glucose metabolized via the pentose phosphate pathway. 

PMID- 25378404
TI  - Negatively charged amino acids near and in transient receptor potential (TRP)
      domain of TRPM4 channel are one determinant of its Ca2+ sensitivity.
AB  - Transient receptor potential (TRP) channel melastatin subfamily member 4 (TRPM4)
      is a broadly expressed nonselective monovalent cation channel. TRPM4 is activated
      by membrane depolarization and intracellular Ca(2+), which is essential for the
      activation. The Ca(2+) sensitivity is known to be regulated by calmodulin and
      membrane phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate
      (PI(4,5)P2). Although these regulators must play important roles in controlling
      TRPM4 activity, mutation analyses of the calmodulin-binding sites have suggested
      that Ca(2+) binds to TRPM4 directly. However, the intrinsic binding sites in
      TRPM4 remain to be elucidated. Here, by using patch clamp and molecular
      biological techniques, we show that there are at least two functionally different
      divalent cation-binding sites, and the negatively charged amino acids near and in
      the TRP domain in the C-terminal tail of TRPM4 (Asp-1049 and Glu-1062 of rat
      TRPM4) are required for maintaining the normal Ca(2+) sensitivity of one of the
      binding sites. Applications of Co(2+), Mn(2+), or Ni(2+) to the cytosolic side
      potentiated TRPM4 currents, increased the Ca(2+) sensitivity, but were unable to
      evoke TRPM4 currents without Ca(2+). Mutations of the acidic amino acids near and
      in the TRP domain, which are conserved in TRPM2, TRPM5, and TRPM8, deteriorated
      the Ca(2+) sensitivity in the presence of Co(2+) or PI(4,5)P2 but hardly affected
      the sensitivity to Co(2+) and PI(4,5)P2. These results suggest a novel role of
      the TRP domain in TRPM4 as a site responsible for maintaining the normal Ca(2+)
      sensitivity. These findings provide more insights into the molecular mechanisms
      of the regulation of TRPM4 by Ca(2+). 

PMID- 25378405
TI  - Sestrin2 protein positively regulates AKT enzyme signaling and survival in human
      squamous cell carcinoma and melanoma cells.
AB  - Skin cancer is the most common cancer in the United States and is mainly caused
      by environmental UV radiation. Reducing skin cancer incidence is becoming an
      urgent issue. The stress-inducible protein Sestrin2 (Sesn2) plays an important
      role in maintaining redox and metabolic homeostasis and their related
      pathologies. However, the role of Sesn2 in cancer remains unclear. Here we show
      that UVB radiation induces Sesn2 expression in normal human keratinocytes, mouse
      skin, normal human melanocytes, and melanoma cells. In addition, Sesn2 promotes
      AKT activation through a PTEN-dependent mechanism. Sesn2 deletion or knockdown
      sensitizes squamous cell carcinoma (SCC) cells to 5-fluorouracil-induced
      apoptosis and melanoma cells to UVB- and vemurafenib-induced apoptosis. In mice
      Sesn2 knockdown suppresses tumor growth from injected human SCC and melanoma
      cells. Last, as compared with normal skin, Sesn2 is up-regulated in both human
      skin SCC and melanoma. Our findings demonstrate that Sesn2 promotes AKT
      activation and survival in response to UVB stress and chemotherapeutics and
      suggest that Sesn2 is oncogenic in skin SCC and melanoma. 

PMID- 25378406
TI  - Nucleosome-specific, time-dependent changes in histone modifications during
      activation of the early growth response 1 (Egr1) gene.
AB  - Histone post-translational modifications and nucleosome remodeling are coordinate
      events involved in eukaryotic transcriptional regulation. There are relatively
      few data on the time course with which these events occur in individual
      nucleosomes. As a contribution to fill this gap, we first describe the nature and
      time course of structural changes in the nucleosomes -2, -1, and +1 of the murine
      Egr1 gene upon induction. To initiate the transient activation of the gene, we
      used the stimulation of MLP29 cells with phorbol esters and the in vivo
      activation after partial hepatectomy. In both models, nucleosomes -1 and +1 are
      partially evicted, whereas nucleosomes +1 and -2 slide downstream during
      transcription. The sliding of the latter nucleosome allows the EGR1 protein to
      bind its site, resulting in the repression of the gene. To decide whether EGR1 is
      involved in the sliding of nucleosome -2, Egr1 was knocked down. In the absence
      of detectable EGR1, the nucleosome still slides and remains downstream longer
      than in control cells, suggesting that the product of the gene may be rather
      involved in the returning of the nucleosome to the basal position. Moreover, the
      presence of eight epigenetic histone marks has been determined at a
      mononucleosomal level in that chromatin region. H3S10phK14ac, H3K4me3, H3K9me3,
      and H3K27me3 are characteristic of nucleosome +1, and H3K9ac and H4K16ac are
      mainly found in nucleosome -1, and H3K27ac predominates in nucleosomes -2 and -1.
      The temporal changes in these marks suggest distinct functions for some of them,
      although changes in H3K4me3 may result from histone turnover. 

PMID- 25378407
TI  - Phosphorylation of rat melanopsin at Ser-381 and Ser-398 by light/dark and its
      importance for intrinsically photosensitive ganglion cells (ipRGCs) cellular Ca2+
      signaling.
AB  - The G protein-coupled light-sensitive receptor melanopsin is involved in non
      image-forming light responses including circadian timing. The predicted secondary
      structure of melanopsin indicates a long cytoplasmic tail with many potential
      phosphorylation sites. Using bioinformatics, we identified a number of amino
      acids with a high probability of being phosphorylated. We generated antibodies
      against melanopsin phosphorylated at Ser-381 and Ser-398, respectively. The
      antibody specificity was verified by immunoblotting and immunohistochemical
      staining of HEK-293 cells expressing rat melanopsin mutated in Ser-381 or Ser
      398. Using the antibody recognizing phospho-Ser-381 melanopsin, we demonstrated
      by immunoblotting and immunohistochemical staining in HEK-293 cells expressing
      rat melanopsin that the receptor is phosphorylated in this position during the
      dark and dephosphorylated when light is turned on. On the contrary, we found that
      melanopsin at Ser-398 was unphosphorylated in the dark and became phosphorylated
      after light stimulation. The light-induced changes in phosphorylation at both Ser
      381 and Ser-398 were rapid and lasted throughout the 4-h experimental period.
      Furthermore, phosphorylation at Ser-381 and Ser-398 was independent of each
      other. The changes in phosphorylation were confirmed in vivo by
      immunohistochemical staining of rat retinas during light and dark. We further
      demonstrated that mutation of Ser-381 and Ser-398 in melanopsin-expressing HEK
      293 cells affected the light-induced Ca(2+) response, which was significantly
      reduced as compared with wild type. Examining the light-evoked Ca(2+) response in
      a melanopsin Ser-381 plus Ser-398 double mutant provided evidence that the
      phosphorylation events were independent. 

PMID- 25378408
TI  - The human antimicrobial peptide LL-37 binds directly to CsrS, a sensor histidine
      kinase of group A Streptococcus, to activate expression of virulence factors.
AB  - Group A Streptococcus (GAS) responds to subinhibitory concentrations of LL-37 by
      up-regulation of virulence factors through the CsrRS (CovRS) two-component
      system. The signaling mechanism, however, is unclear. To determine whether LL-37
      signaling reflects specific binding to CsrS or rather a nonspecific response to
      LL-37-mediated membrane damage, we tested LL-37 fragments for CsrRS signaling and
      for GAS antimicrobial activity. We identified a 10-residue fragment (RI-10) of LL
      37 as the minimal peptide that retains the ability to signal increased expression
      of GAS virulence factors, yet it has no detectable antimicrobial activity against
      GAS. Substitution of individual key amino acids in RI-10 reduced or abrogated
      signaling. These data do not support the hypothesis that CsrS detects LL-37
      induced damage to the bacterial cell membrane but rather suggest that LL-37
      signaling is mediated by a direct interaction with CsrS. To test whether LL-37
      binds to CsrS, we used the purified CsrS extracellular domain to pull down LL-37
      in vitro, a result that provides further evidence that LL-37 binds to CsrS. The
      dissociation of CsrS-mediated signaling from membrane damage by LL-37 fragments
      together with in vitro evidence for a direct LL-37-CsrS binding interaction
      constitute compelling evidence that signal transduction by LL-37 through CsrS
      reflects a direct ligand/receptor interaction. 

PMID- 25378409
TI  - Multiple drugs compete for transport via the Plasmodium falciparum chloroquine
      resistance transporter at distinct but interdependent sites.
AB  - Mutations in the "chloroquine resistance transporter" (PfCRT) are a major
      determinant of drug resistance in the malaria parasite Plasmodium falciparum. We
      have previously shown that mutant PfCRT transports the antimalarial drug
      chloroquine away from its target, whereas the wild-type form of PfCRT does not.
      However, little is understood about the transport of other drugs via PfCRT or the
      mechanism by which PfCRT recognizes different substrates. Here we show that
      mutant PfCRT also transports quinine, quinidine, and verapamil, indicating that
      the protein behaves as a multidrug resistance carrier. Detailed kinetic analyses
      revealed that chloroquine and quinine compete for transport via PfCRT in a manner
      that is consistent with mixed-type inhibition. Moreover, our analyses suggest
      that PfCRT accepts chloroquine and quinine at distinct but antagonistically
      interacting sites. We also found verapamil to be a partial mixed-type inhibitor
      of chloroquine transport via PfCRT, further supporting the idea that PfCRT
      possesses multiple substrate-binding sites. Our findings provide new mechanistic
      insights into the workings of PfCRT, which could be exploited to design potent
      inhibitors of this key mediator of drug resistance. 

PMID- 25378410
TI  - Structural dynamics as a contributor to error-prone replication by an RNA
      dependent RNA polymerase.
AB  - RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp)
      are attenuated. The ability to predict residues of the RdRp required for faithful
      incorporation of nucleotides represents an essential step in any pipeline
      intended to exploit perturbed fidelity as the basis for rational design of
      vaccine candidates. We used x-ray crystallography, molecular dynamics
      simulations, NMR spectroscopy, and pre-steady-state kinetics to compare a mutator
      (H273R) RdRp from poliovirus to the wild-type (WT) enzyme. We show that the
      nucleotide-binding site toggles between the nucleotide binding-occluded and
      nucleotide binding-competent states. The conformational dynamics between these
      states were enhanced by binding to primed template RNA. For the WT, the occluded
      conformation was favored; for H273R, the competent conformation was favored. The
      resonance for Met-187 in our NMR spectra reported on the ability of the enzyme to
      check the correctness of the bound nucleotide. Kinetic experiments were
      consistent with the conformational dynamics contributing to the established pre
      incorporation conformational change and fidelity checkpoint. For H273R, residues
      comprising the active site spent more time in the catalytically competent
      conformation and were more positively correlated than the WT. We propose that by
      linking the equilibrium between the binding-occluded and binding-competent
      conformations of the nucleotide-binding pocket and other active-site dynamics to
      the correctness of the bound nucleotide, faithful nucleotide incorporation is
      achieved. These studies underscore the need to apply multiple biophysical and
      biochemical approaches to the elucidation of the physical basis for polymerase
      fidelity. 

PMID- 25378411
TI  - Plasminogen activator inhibitor-1 inhibits angiogenic signaling by uncoupling
      vascular endothelial growth factor receptor-2-alphaVbeta3 integrin cross talk.
AB  - OBJECTIVE: Plasminogen activator inhibitor-1 (PAI-1) regulates angiogenesis via
      effects on extracellular matrix proteolysis and cell adhesion. However, no
      previous study has implicated PAI-1 in controlling vascular endothelial growth
      factor (VEGF) signaling. We tested the hypothesis that PAI-1 downregulates VEGF
      receptor-2 (VEGFR-2) activation by inhibiting a vitronectin-dependent cooperative
      binding interaction between VEGFR-2 and alphaVbeta3. APPROACH AND RESULTS: We
      studied effects of PAI-1 on VEGF signaling in human umbilical vein endothelial
      cells. PAI-1 inhibited VEGF-induced phosphorylation of VEGFR-2 in human umbilical
      vein endothelial cells grown on vitronectin, but not on fibronectin or collagen.
      PAI-1 inhibited the binding of VEGFR-2 to beta3 integrin, VEGFR-2 endocytosis,
      and intracellular signaling pathways downstream of VEGFR-2. The anti-VEGF effect
      of PAI-1 was mediated by 2 distinct pathways, one requiring binding to
      vitronectin and another requiring binding to very low-density lipoprotein
      receptor. PAI-1 inhibited VEGF-induced angiogenesis in vitro and in vivo, and
      pharmacological inhibition of PAI-1 promoted collateral arteriole development and
      recovery of hindlimb perfusion after femoral artery interruption. CONCLUSIONS:
      PAI-1 inhibits activation of VEGFR-2 by VEGF by disrupting a vitronectin
      dependent proangiogenic binding interaction involving alphaVbeta3 and VEGFR-2.
      These results broaden our understanding of the roles of PAI-1, vitronectin, and
      endocytic receptors in regulating VEGFR-2 activation and suggest novel
      therapeutic strategies for regulating VEGF signaling.

PMID- 25378412
TI  - Inflammasome activation by mitochondrial oxidative stress in macrophages leads to
      the development of angiotensin II-induced aortic aneurysm.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) is considered a chronic inflammatory
      disease; however, the molecular basis underlying the sterile inflammatory
      response involved in the process of AAA remains unclear. We previously showed
      that the inflammasome, which regulates the caspase-1-dependent interleukin-1beta
      production, mediates the sterile cardiovascular inflammatory responses.
      Therefore, we hypothesized that the inflammasome is a key mediator of initial
      inflammation in AAA formation. APPROACH AND RESULTS: Apoptosis-associated speck
      like protein containing a caspase recruitment domain is highly expressed in
      adventitial macrophages in human and murine AAA tissues. Using an established
      mouse model of AAA induced by continuous infusion of angiotensin II in Apoe(-/-)
      mice, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck
      like protein containing a caspase recruitment domain, and caspase-1 deficiency in
      Apoe(-/-) mice were shown to decrease the incidence, maximal diameter, and
      severity of AAA along with adventitial fibrosis and inflammatory responses
      significantly, such as inflammatory cell infiltration and cytokine expression in
      the vessel wall. NLRP3, apoptosis-associated speck-like protein containing a
      caspase recruitment domain, and caspase-1 deficiency in Apoe(-/-) mice also
      reduced elastic lamina degradation and metalloproteinase activation in the early
      phase of AAA formation. Furthermore, angiotensin II stimulated generation of
      mitochondria-derived reactive oxygen species in the adventitial macrophages, and
      this mitochondria-derived reactive oxygen species generation was inhibited by
      NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment
      domain, and caspase-1 deficiency. In vitro experiments revealed that angiotensin
      II stimulated the NLRP3 inflammasome activation and subsequent interleukin-1beta
      release in macrophages, and this activation was mediated through an angiotensin
      type I receptor/mitochondria-derived reactive oxygen species-dependent pathway.
      CONCLUSIONS: Our results demonstrate the importance of the NLRP3 inflammasome in
      the initial inflammatory responses in AAA formation, indicating its potential as
      a novel therapeutic target for preventing AAA progression.

PMID- 25378414
TI  - Videoscopic inguinal lymphadenectomy in malignant melanoma: safe in pregnancy?
AB  - Lymphadenectomy is the standard of care for metastatic melanoma in the inguinal
      lymph node basin. Historically, open surgery was the only treatment option.
      However, in recent years, videoscopic inguinal lymphadenectomy (VIL) has become a
      popular approach as it offers a minimally invasive alternative, provides similar
      oncologic control and reduces wound complications. Even though the VIL approach
      is being used more frequently, the patient populations that stand to benefit the
      most from this approach are still under investigation. Despite continued advances
      in safety for laparoscopic surgery, many surgeons are hesitant to perform these
      procedures on pregnant women. In this report, we present a successful VIL in a
      pregnant patient, describe our technique and demonstrate the safety of performing
      VIL in expectant mothers. To our knowledge, this case represents the first VIL
      performed in an expectant mother. 

PMID- 25378415
TI  - Abscess formation within a Rathke's cleft cyst.
AB  - We report and discuss the rare case of a pituitary abscess forming within a
      Rathke's cleft cyst (RCC). A 66-year-old gentleman presented with visual
      deterioration and symptoms suggestive of hypopituitarism. The patient underwent
      transsphenoidal debulking of the lesion whereupon purulent material was
      discovered. Histological examination was suggestive of RCC together with numerous
      neutrophils characteristic of abscess. Microbiological culture of the material
      grew Staphylococcus aureus. The patient was treated for a RCC abscess and
      received antibiotics and endocrine replacement therapy. The patient has been
      followed up for 2 years without recurrence. Although uncommon, we recommend the
      consideration of RCC abscess as a differential diagnosis of a pituitary mass
      lesion as clinical presentation and radiological assessment are not specific in
      identifying these lesions preoperatively. 

PMID- 25378413
TI  - Inhibition of FOXO1/3 promotes vascular calcification.
AB  - OBJECTIVE: Vascular calcification is a characteristic feature of atherosclerosis,
      diabetes mellitus, and end-stage renal disease. We have demonstrated that
      activation of protein kinase B (AKT) upregulates runt-related transcription
      factor 2 (Runx2), a key osteogenic transcription factor that is crucial for
      calcification of vascular smooth muscle cells (VSMC). Using mice with SMC
      specific deletion of phosphatase and tensin homolog (PTEN), a major negative
      regulator of AKT, the present studies uncovered a novel molecular mechanism
      underlying PTEN/AKT/FOXO (forkhead box O)-mediated Runx2 upregulation and VSMC
      calcification. APPROACH AND RESULTS: SMC-specific PTEN deletion mice were
      generated by crossing PTEN floxed mice with SM22alpha-Cre transgenic mice. The
      PTEN deletion resulted in sustained activation of AKT that upregulated Runx2 and
      promoted VSMC calcification in vitro and arterial calcification ex vivo. Runx2
      knockdown did not affect proliferation but blocked calcification of the PTEN
      deficient VSMC, suggesting that PTEN deletion promotes Runx2-depedent VSMC
      calcification that is independent of proliferation. At the molecular level, PTEN
      deficiency increased the amount of Runx2 post-transcriptionally by inhibiting
      Runx2 ubiquitination. AKT activation increased phosphorylation of FOXO1/3 that
      led to nuclear exclusion of FOXO1/3. FOXO1/3 knockdown in VSMC phenocopied the
      PTEN deficiency, demonstrating a novel function of FOXO1/3, as a downstream
      signaling of PTEN/AKT, in regulating Runx2 ubiquitination and VSMC calcification.
      Using heterozygous SMC-specific PTEN-deficient mice and atherogenic ApoE(-/-)
      mice, we further demonstrated AKT activation, FOXO phosphorylation, and Runx2
      ubiquitination in vascular calcification in vivo. CONCLUSIONS: Our studies have
      determined a new causative effect of SMC-specific PTEN deficiency on vascular
      calcification and demonstrated that FOXO1/3 plays a crucial role in PTEN/AKT
      modulated Runx2 ubiquitination and VSMC calcification.

PMID- 25378416
TI  - Are patient- or procedure-related factors relevant to middle-term cognitive
      decline after cardiac surgery? This is the question.

PMID- 25378417
TI  - Research using qualitative, quantitative or mixed methods and choice based on the
      research.
AB  - Research is fundamental to the advancement of medicine and critical to
      identifying the most optimal therapies unique to particular societies. This is
      easily observed through the dynamics associated with pharmacology, surgical
      technique and the medical equipment used today versus short years ago.
      Advancements in knowledge synthesis and reporting guidelines enhance the quality,
      scope and applicability of results; thus, improving health science and clinical
      practice and advancing health policy. While advancements are critical to the
      progression of optimal health care, the high cost associated with these endeavors
      cannot be ignored. Research fundamentally needs to be evaluated to identify the
      most efficient methods of evaluation. The primary objective of this paper is to
      look at a specific research methodology when applied to the area of clinical
      research, especially extracorporeal circulation and its prognosis for the future.

PMID- 25378418
TI  - Dangerous surgical scavenger hunt: the complicated course of a patient with left
      ventricular assist device and end-stage renal disease undergoing reconstructive
      flap surgery.
AB  - Patients with left ventricular assist devices (LVADs) who develop stage IV sacral
      pressure sores (SPS) have an increased procedural risk. We present the
      complications, including severe intra- and postoperative bleeding, diarrhea with
      metabolic acidosis, volume loss and acute on chronic renal failure, flap
      dehiscence and late LVAD outflow cannula thrombosis, in a 54-year-old male who
      underwent diverting ileostomy (DI) and subsequent fasciocutaneous flap (FCF)
      surgery for stage IV SPS while supported with an LVAD. Our experience suggests
      that, despite continuous heparinization, life-threatening thrombotic
      complications, such as device clotting, can occur. Therefore, the benefit of
      intervention has to outweigh the risk of bleeding, which should be managed with
      meticulous surgical technique and substitution of red blood cells rather than the
      reversal of heparinization or the substitution of clotting factors. Continuation
      of double anti-platelet therapy should also be considered. 

PMID- 25378419
TI  - Who should we blame for the death of Baby P?

PMID- 25378420
TI  - Cerebral venous thrombosis in the absence of headache.
AB  - BACKGROUND AND PURPOSE: Although headache is the most common symptom in cerebral
      venous thrombosis, 5% to 30% of patients do not report headache at baseline.
      Characteristics of these patients have not been investigated. METHODS: In post
      hoc analysis of the International Study on Cerebral Vein and Dural Sinus
      Thrombosis study, patients who might not have been able to report headache
      (aphasia, stupor, coma, or mental status disorder) were excluded. RESULTS: Three
      hundred eighty-two of the original 624 patients (61%) were included, of whom 38
      (10%) did not report headache at baseline. Patients without headache were older
      (mean age, 45 versus 37; P=0.001) and less often female (63% versus 77%; P=0.06).
      Paresis (42% versus 27%; P=0.05) and seizures (58% versus 32%; P=0.001) were more
      common in patients without headache, whereas papilledema was less common (8%
      versus 35%; P=0.001). Isolated cortical vein thrombosis (16% versus 2%; P=0.001),
      brain parenchymal lesions (66% versus 46%; P=0.02), and malignancies (18% versus
      6%; P=0.009) were more common among patients without headache. Outcome at last
      follow-up was worse in patients without headache (modified Rankin Scale, 0-1; 76%
      versus 89%; P=0.04; mortality, 13% versus 5%; P=0.05), but after adjustment for
      prognostic variables, headache was not an independent predictor of outcome.
      CONCLUSIONS: Patients with cerebral venous thrombosis but without headache are a
      heterogeneous subgroup, in which older patients, men, and some associated
      conditions are over-represented. Patients without headache had a worse clinical
      outcome, but after adjustment for imbalances, headache was not an independent
      predictor of outcome.

PMID- 25378421
TI  - Off-hours admission and acute stroke care quality: a nationwide study of
      performance measures and case-fatality.
AB  - BACKGROUND AND PURPOSE: Studies have reported higher risks of death and other
      adverse outcomes in acute stroke patients admitted off-hours; however, little is
      known about the underlying mechanisms. According to time of admission, our aim
      was to examine compliance with performance measures for acute stroke care
      processes, including the effect of a systematic quality improvement program, and
      to examine 30 days case-fatality. METHODS: A population-based historical cohort
      study, including patients admitted to Danish hospitals with a first ever acute
      stroke (January 1, 2003, to December 31, 2011; N=64 975). Off-hours were weekends
      and evening and nighttime shifts on weekdays. Compliance with performance
      measures was compared using general linear modeling, and odds ratios for 30 days
      case-fatality were obtained using multivariable logistic regression. RESULTS:
      Patients admitted off-hours had a lower chance of compliance with 8 out of 10
      performance measures; however, these differences diminished over time. Unadjusted
      odds ratio for 30 days case-fatality, for patients admitted off-hours compared
      with patients admitted on-hours, was 1.15 (95% confidence interval, 1.09-1.21).
      Adjusting for patient characteristics (in particular, stroke severity) decreased
      the odds ratio to 1.03 (95% confidence interval, 0.97-1.10). Additional
      adjustment for hospital characteristics and compliance with performance measures
      had no effect on the odds ratio. CONCLUSION: Patients admitted off-hours received
      a poorer quality of care. However, the admission time-related differences in care
      were substantially reduced over time, and the differences in 30 days case
      fatality appeared primarily to be explained by differences in stroke severity.

PMID- 25378422
TI  - Antithrombotic therapy after acute ischemic stroke in patients with atrial
      fibrillation.
AB  - BACKGROUND AND PURPOSE: For patients with atrial fibrillation and ischemic stroke
      (IS), current guidelines recommend oral anticoagulation (OAC) alone for secondary
      prevention of IS. In a large prospective cohort of patients with acute IS and
      atrial fibrillation, we determine the association between antithrombotic regimen
      on discharge and risk of major vascular events. METHODS: Prospective cohort of
      consecutive patients included in the Ontario Stroke Registry. Multivariable Cox
      proportional hazard models were used to determine the association between
      antithrombotic regimen on discharge and time to death or admission for recurrent
      IS, myocardial infarction, or major bleeding. RESULTS: Two thousand one hundred
      sixty-two patients were hospitalized atrial fibrillation and acute IS. At
      discharge, 8.0% were prescribed no antithrombotic therapy, 21.6% antiplatelet
      therapy alone, 39.3% OAC (warfarin) alone, and 31.1% combination OAC and
      antiplatelet therapy. Compared with OAC alone (hazard ratio [HR], 1.0), no
      antithrombotic therapy (HR, 1.51; 95% confidence interval, 1.23-1.86) and
      antiplatelet therapy (HR, 1.31; 95% confidence interval, 1.14-1.50) were
      associated with an increased risk of the primary composite outcome, whereas
      combination OAC and antiplatelet therapy was associated with a trend toward a
      reduced risk (HR, 0.91; 95% confidence interval, 0.80-1.04 overall and HR, 0.79;
      95% confidence interval, 0.61-1.02 in those with coronary heart disease). Results
      were consistent in those with severe stroke: HR 1.58 (95% CI, 1.21-2.06), 1.34
      (95% CI, 1.09-1.63), and 0.91 (95% CI, 0.74-1.11), respectively. CONCLUSIONS:
      Contrary to current guidelines, 30% of patients with atrial fibrillation and
      recent IS are not prescribed any OAC therapy on discharge, whereas a further 30%
      are prescribed combination OAC and antiplatelet therapy. Combination OAC and
      antiplatelet therapy in patients at high cardiovascular risk requires evaluation
      in clinical trials, particularly with the newer OACs, given their more favorable
      risk-benefit ratio compared with warfarin.

PMID- 25378423
TI  - Some common misperceptions about P values.

PMID- 25378424
TI  - Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic
      stroke: a multicentric, randomized trial.
AB  - BACKGROUND AND PURPOSE: Pilot studies have suggested benefit from intravenous
      administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We
      explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke.
      METHODS: This was a phase II, multicenter, parallel group, randomized trial with
      blinded outcome assessment that included 120 patients. Patients with subacute
      ischemic stroke were randomly assigned to the arm that received intravenous
      infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy
      outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary
      outcomes were change in infarct volume, National Institute of Health Stroke Scale
      (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area
      of (18)fluorodeoxyglucose positron emission tomography uptake in any body part
      over 365 days. RESULTS: Fifty-eight patients received a mean of 280.75 million
      BMSCs at median of 18.5 days after stroke onset. There was no significant
      difference between BMSCs arm and control arm in the Barthel Index score (63.1
      versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3
      (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in
      infarct volume (-11.1 versus -7.36; P=0.63) at day 180. Adverse events were also
      similar in the 2 arms, and no patient showed any new area of
      (18)fluorodeoxyglucose uptake. CONCLUSIONS: With the methods used, results of
      this hitherto first randomized controlled trial indicate that intravenous
      infusion of BMSCs is safe, but there is no beneficial effect of treatment on
      stroke outcome. CLINICAL TRIAL REGISTRATION: URLs:
      http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique
      identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.

PMID- 25378425
TI  - Hospitalization within the first year after stroke: the Dijon stroke registry.
AB  - BACKGROUND AND PURPOSE: This population-based study aimed to identify unplanned
      hospitalization within the first year after stroke to determine factors
      associated with it and consequences on survival. METHODS: All first-ever acute
      strokes occurring in Dijon, France, from 2009 to 2011, were prospectively
      collected from a population-based registry. Demographics and clinical data,
      including stroke severity measured by the National Institutes of Health Stroke
      Scale and disability after stroke, were recorded. For each patient, the first
      unplanned hospitalization that occurred within 1 year after stroke was retrieved
      by linking data with the national French Hospital Discharge Database. Predictors
      of hospitalization and survival at 1 year were identified using logistic
      regression models. RESULTS: Among the 613 patients recorded, 94 (15.3%) were
      excluded because of early death. Of the 519 remaining patients, 167 (32.2%) were
      hospitalized at 1 year. Subsequent hospitalization led to in-hospital death for
      16 (9.6%) patients. In multivariable analyses, only a history of hypertension and
      atrial fibrillation were associated with hospitalization. In stratified analyses,
      the National Institutes of Health Stroke Scale score was associated with a higher
      risk of hospitalization (odds ratio, 1.13; 95% confidence interval, 1.03-1.22;
      P=0.006), whereas only a trend was noted for disability (odds ratio, 2.26; 95%
      confidence interval, 0.82-6.22; P=0.113) in patients who returned home after the
      index stroke. Hospitalization was negatively associated with being alive at 1
      year (odds ratio, 0.36; 95% confidence interval, 0.19-0.66; P<0.01). CONCLUSIONS:
      Stroke survivors are at high risk of hospitalization after the episode, and
      subsequent admission is associated with poor survival, thus highlighting the need
      for follow-up interventions after discharge to prevent readmission.

PMID- 25378426
TI  - Efficacy of synchronous verbal training during repetitive transcranial magnetic
      stimulation in patients with chronic aphasia.
AB  - BACKGROUND AND PURPOSE: Although multiple studies have suggested that repetitive
      transcranial magnetic stimulation (rTMS) may facilitate recovery after stroke,
      the efficacy of synchronous speech therapy integrated with an rTMS protocol has
      yet to be determined. We investigated language responses to this strategy and
      determined the longevity of the resulting therapeutic outcomes. METHODS: Forty
      five patients with stroke who presented with nonfluent aphasia were randomly
      assigned to the TMSsyn group and underwent synchronous picture-naming training
      together with contralesional 1 Hz-rTMS for 10 daily sessions. The TMSsub group
      underwent subsequent picture-naming activity after the primed 1 Hz-rTMS, and the
      TMSsham group received concurrent naming task along with the sham 1 Hz-rTMS. The
      Concise Chinese Aphasia test and the picture-naming test were performed before,
      immediately, and after 3 months of the intervention. RESULTS: TMSsyn showed
      significantly superior results in Concise Chinese Aphasia test score (P<0.001),
      expression and description subtests (P<0.001), and action (P=0.02) and object
      naming activity (P=0.008); the superior results lasted for 3 months (P=0.005), in
      comparison with the TMSsub and TMSsham groups. CONCLUSIONS: We established a real
      time model that involved implementing verbal tasks together with the rTMS
      protocol. Our results confirmed that the strategy yielded favorable outcomes that
      were of considerable longevity. The results also indicated that the rTMS protocol
      and language training can be combined to achieve outcomes superior to those
      obtained when used separately. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT02120508.

PMID- 25378427
TI  - Response to letter regarding article, "socioeconomic status inconsistency and
      risk of stroke among Japanese middle-aged women".

PMID- 25378428
TI  - Response to letter regarding article, "time and diffusion lesion size in major
      anterior circulation ischemic strokes".

PMID- 25378429
TI  - Embolic strokes of undetermined source in the Athens stroke registry: a
      descriptive analysis.
AB  - BACKGROUND AND PURPOSE: A new clinical construct termed embolic stroke of
      undetermined source (ESUS) was recently introduced, but no such population has
      been described yet. Our aim is to provide a detailed descriptive analysis of an
      ESUS population derived from a large prospective ischemic stroke registry using
      the proposed diagnostic criteria. METHODS: The criteria proposed by the
      Cryptogenic Stroke/ESUS International Working Group were applied to the Athens
      Stroke Registry to identify all ESUS patients. ESUS was defined as a
      radiologically confirmed nonlacunar brain infarct in the absence of (a)
      extracranial or intracranial atherosclerosis causing >=50% luminal stenosis in
      arteries supplying the ischemic area, (b) major-risk cardioembolic source, and
      (c) any other specific cause of stroke. RESULTS: Among 2735 patients admitted
      between 1992 and 2011, 275 (10.0%) were classified as ESUS. In the majority of
      ESUS (74.2%), symptoms were maximal at onset. ESUS were of moderate severity
      (median National Institute Health Stroke Scale score, 5). The most prevalent risk
      factor was arterial hypertension (64.7%), and 50.9% of patients were
      dyslipidemic. Among potential causes of the ESUS, covert atrial fibrillation (AF)
      was the most prevalent: in 30 (10.9%) patients, AF was diagnosed during
      hospitalization for stroke recurrence, whereas in 50 (18.2%) patients AF was
      detected after repeated ECG monitoring during follow-up. Also, covert AF was
      strongly suggested in 38 patients (13.8%) but never recorded. CONCLUSIONS: About
      10% of patients with first-ever ischemic stroke met criteria for ESUS; covert
      paroxysmal AF seems to be a frequent cause of ESUS.

PMID- 25378431
TI  - Letter by Dai et al regarding article, "time and diffusion lesion size in major
      anterior circulation ischemic strokes".

PMID- 25378433
TI  - Is the United Nations catching up with Ebola at last?

PMID- 25378432
TI  - Amplification of regulatory T cells using a CD28 superagonist reduces brain
      damage after ischemic stroke in mice.
AB  - BACKGROUND AND PURPOSE: Neuroinflammation plays an important role in ischemic
      brain injury. Regulatory T cells (Treg) are important endogenous immune
      modulators. We tested the hypothesis that Treg amplification with a CD28
      superagonistic monoclonal antibody (CD28SA) reduces brain damage in murine
      cerebral ischemia. METHODS: Cerebral ischemia was induced by coagulation of the
      distal middle cerebral artery or by 60 minutes filament occlusion of the proximal
      middle cerebral artery in C57BL6 mice. 150 MUg CD28SA was injected
      intraperitoneally 3 or 6 hours after ischemia onset. Outcome was determined by
      infarct volumetry and behavioral testing. Brain-infiltrating leukocyte
      subpopulations were analyzed by flow cytometry and immunohistochemistry 3 and 7
      days after middle cerebral artery occlusion. RESULTS: CD28SA reduced infarct size
      in both models and attenuated functional deficit 7 days after stroke induction.
      Mice treated with CD28SA increased numbers of Treg in spleen and brain. Tregs
      were functionally active and migrated into the brain where they accumulated and
      proliferated in the peri-infarct area. More than 60% of brain infiltrating Treg
      produced interleukin-10 in CD28SA compared with 30% in control. CONCLUSIONS: In
      vivo expansion and amplification of Treg by CD28SA attenuates the inflammatory
      response and improves outcome after experimental stroke.

PMID- 25378430
TI  - Pathogenic ischemic stroke phenotypes in the NINDS-stroke genetics network.
AB  - BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and
      Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic
      stroke studies that aims to generate high-quality phenotype data to identify the
      genetic basis of pathogenic stroke subtypes. This analysis characterizes the
      etiopathogenetic basis of ischemic stroke and reliability of stroke
      classification in the consortium. METHODS: Fifty-two trained and certified
      adjudicators determined both phenotypic (abnormal test findings categorized in
      major pathogenic groups without weighting toward the most likely cause) and
      causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed
      ischemic stroke from 12 US studies and 11 studies from 8 European countries using
      the web-based Causative Classification of Stroke System. Classification
      reliability was assessed with blinded readjudication of 1509 randomly selected
      cases. RESULTS: The distribution of pathogenic categories varied by study, age,
      sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given
      major ischemic stroke pathogenesis (phenotypic subtype) were classified into the
      same final causative category with high confidence. There was good agreement for
      both causative (kappa 0.72; 95% confidence interval, 0.69-0.75) and phenotypic
      classifications (kappa 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS:
      This study demonstrates that pathogenic subtypes can be determined with good
      reliability in studies that include investigators with different expertise and
      background, institutions with different stroke evaluation protocols and
      geographic location, and patient populations with different epidemiological
      characteristics. The discordance between phenotypic and causative stroke subtypes
      highlights the fact that the presence of an abnormality in a patient with stroke
      does not necessarily mean that it is the cause of stroke.

PMID- 25378434
TI  - Deciphering oncogenic drivers: from single genes to integrated pathways.
AB  - Technological advances in next-generation sequencing have uncovered a wide
      spectrum of aberrations in cancer genomes. The extreme diversity in cancer
      mutations necessitates computational approaches to differentiate between the
      'drivers' with vital function in cancer progression and those nonfunctional
      'passengers'. Although individual driver mutations are routinely identified,
      mutational profiles of different tumors are highly heterogeneous. There is
      growing consensus that pathways rather than single genes are the primary target
      of mutations. Here we review extant bioinformatics approaches to identifying
      oncogenic drivers at different mutational levels, highlighting the strategies for
      discovering driver pathways and networks from cancer mutation data. These
      approaches will help reduce the mutation complexity, thus providing a simplified
      picture of cancer. 

PMID- 25378435
TI  - Network inference from AP-MS data: computational challenges and solutions.
AB  - Protein-protein interaction is of primary importance to understand protein
      functions. In recent years, the high-throughput AP-MS experiments have generated
      a large amount of bait-prey data, posing great challenges on the computational
      analysis of such data for inferring true interactions and protein complexes. To
      date, many research efforts have been devoted to developing novel computational
      methods to analyze these AP-MS data sets. In this article, we review and classify
      the key computational methods developed for the inference of protein-protein
      interactions and the detection of protein complexes from the AP-MS experiments.
      We hope that our review as well as the challenges highlighted in the article will
      provide valuable insights into driving future research for further advancing the
      state-of-the-art technologies in computational prediction, characterization and
      analysis of protein-protein interactions and protein complexes from the AP-MS
      data. 

PMID- 25378436
TI  - Practical performance of tree comparison metrics.
AB  - The phylogenetic literature contains numerous measures for assessing differences
      between two phylogenetic trees. Individual measures have been criticized on
      various grounds, but little is known about their comparative performance in
      typical applications. We evaluate the performance of nine tree distance measures
      on two tasks: 1) distinguishing trees separated by lesser versus greater numbers
      of recombinations, and 2) distinguishing trees inferred with lower versus higher
      quality data. We find that when the trees being compared are similar, measures
      that make use of branch lengths are superior, with the branch-length version of
      the Robinson-Foulds metric performing best. In contrast, for dissimilar trees
      topology-only measures are superior, with the Alignment metric of Nye et al.
      performing best. We also apply the measures to a mammalian dataset and observe
      that the best metric depends on whether branch-length information is of interest.
      We give practical recommendations for choosing a tree distance metric in
      different applications. 

PMID- 25378437
TI  - Health charities call on UK prime minister to put prevention at top of agenda.

PMID- 25378438
TI  - Advancing paternal age and schizophrenia: the impact of delayed fatherhood.
AB  - OBJECTIVE: It is well known that advancing paternal age is associated with an
      increased risk of schizophrenia in offspring, but the mechanism behind this
      association remains unknown. This study investigates if delayed fatherhood rather
      than advancing paternal age per se might explain the increased risk of
      schizophrenia in offspring associated with advancing paternal age. METHODS: This
      is a register-based study of the Swedish population looking at people born 1955
      1985 who have 1 or 2 siblings (n = 2 589 502). The main analysis investigated
      whether the association between advancing paternal age and schizophrenia was
      explained by delayed fatherhood. Possible confounding factors were taken into
      account. Cox regression was used throughout. RESULTS: In the main analysis the
      association between advancing paternal age and increased risk of schizophrenia in
      offspring disappeared after controlling for delayed fatherhood (hazard ratio [HR]
      = 0.93, 95% CI = 0.72-1.21 comparing 45+ years old fathers to those 25-29),
      whereas delayed fatherhood showed an association with increased risk of
      schizophrenia in offspring comparing 35-39 and 40-44 years old fathers to 25-29
      year olds (HR = 1.37, 95% CI = 1.18-1.58; HR = 1.81, 95% CI = 1.44-2.28,
      respectively). The results remained when controlling for possible confounders.
      CONCLUSIONS: This study suggests that the association between paternal age and
      schizophrenia is not due to paternal age per se, but rather to an unknown factor
      associated with both delayed fatherhood and schizophrenia.

PMID- 25378444
TI  - Addressing health and well-being of U.S. Chinese older adults through community
      based participatory research: introduction to the PINE Study.
AB  - The PINE Study--the Population Study of ChINese Elderly in Chicago is a
      population-based epidemiological study of U.S. Chinese older adults in the
      greater Chicago area with primary aims to examine their health status and well
      being. This special issue is designed to expand our current understanding on the
      health status, medical conditions, and well-being of U.S. Chinese older adults
      using findings from the PINE Study. In this article, we present research design,
      study findings, and important implications for researchers, community
      gatekeepers, and health care professionals. Through the information reported in
      this special issue, we call for increased family and community care, improved
      delivery of care, practice changes, and policy reform, to prepare for the growing
      numbers of minority older adults in dire need of culturally and linguistically
      appropriate health and social services.

PMID- 25378445
TI  - The prevalence of medical conditions among U.S. Chinese community-dwelling older
      adults.
AB  - BACKGROUND: The burden of medical conditions is increasing among U.S. older
      adults, yet we have very limited knowledge about medical conditions among Chinese
      older adults in the United States. This study aimed to examine the prevalence of
      medical conditions and its sociodemographic and health-related correlates within
      the context of a population-based cohort study of U.S. Chinese older adults.
      METHOD: Using a community-based participatory research approach, community
      dwelling Chinese older adults aged 60 years and older in the Greater Chicago area
      were interviewed between 2011 and 2013. RESULTS: Of the 3,159 participants
      interviewed, 58.9% were female and the mean age was 72.8 years. In total, 84.3%
      of older adults had one or more medical condition, 24.6% reported two conditions,
      19.5% had three conditions, and 17.0% reported four or more conditions. A
      sizeable percentage of older adults had never been screened for dyslipidemia
      (24.4%) or had never been screened for diabetes mellitus (35.7%).For those who
      reported high cholesterol, 73.0% were taking medications when compared with 76.1%
      of those who reported having diabetes and 88.3% of those who reported having high
      blood pressure. Various sociodemographic and health-related characteristics were
      correlated with medical conditions. CONCLUSION: Medical conditions were common
      among U.S. Chinese older adults, yet screening and treatment rates were fairly
      low. Future longitudinal studies should be conducted to better understand the
      risk and protective factors associated with medical conditions.

PMID- 25378446
TI  - Physical function assessment in a community-dwelling population of U.S. Chinese
      older adults.
AB  - BACKGROUND: This report describes the levels of physical function in U.S. Chinese
      older adults utilizing self-reported and performance-based measures, and examines
      the association between sociodemographic characteristics and physical function.
      METHODS: The Population Study of Chinese Elderly in Chicago enrolled an
      epidemiological cohort of 3,159 community-dwelling Chinese older adults aged 60
      and older. We collected self-reported physical function using Katz activities of
      daily living and Lawton instrumental activities of daily living items, the Index
      of Mobility scale, and the Index of Basic Physical Activities scale. Participants
      were also asked to perform tasks in chair stand, tandem stand, and timed walk. We
      computed Pearson and Spearman correlation coefficients to examine the correlation
      between sociodemographic and physical function variables. RESULTS: A total of
      7.8% of study participants experienced activities of daily living impairment, and
      50.2% experienced instrumental activities of daily living impairment. With
      respect to physical performance testing, 11.4% of the participants were not able
      to complete chair stand for five times, 8.5% of the participants were unable to
      do chair stands at all. Older age, female gender, lower education level, being
      unmarried, living with fewer people in the same household, having fewer children,
      living fewer years in the United States, living fewer years in the community, and
      worsening health status were significantly correlated with lower levels of
      physical function. CONCLUSIONS: Utilizing self-reported and performance-based
      measures of physical function in a large population-based study of U.S. Chinese
      older adults, our findings expand current understanding of minority older adults'
      functional status.

PMID- 25378447
TI  - The prevalence of cardiopulmonary symptoms among Chinese older adults in the
      Greater Chicago area.
AB  - BACKGROUND: Cardiovascular and pulmonary symptoms influence health and well-being
      among older adults. However, minority aging populations are often
      underrepresented in most studies on cardiovascular and pulmonary symptoms. This
      study aims to examine the prevalence of cardiovascular and pulmonary symptoms
      among U.S. Chinese older adults. METHODS: Data were drawn from the Population
      Study of Chinese Elderly study, a population-based survey of U.S. Chinese older
      adults in the Greater Chicago area. Guided by a community-based participatory
      research approach, a total of 3,159 Chinese older adults aged 60 and above were
      surveyed. Clinical Review of Systems was used to assess participants' perceptions
      of their cardiovascular and pulmonary symptoms. RESULTS: Cardiovascular symptoms
      (31.6%) and pulmonary symptoms (42.2%) were commonly experienced by U.S. Chinese
      older adults. Symptoms such as cough (27.4%), sputum production (22.7%), chest
      pain or discomfort (16.3%), shortness of breath at rest (15.1%), and shortness of
      breath with activity (12.9%) were commonly reported. Older age, lower income,
      fewer years residing in the community, poorer self-perceived health status and
      quality of life, and worsened health over the last year were associated with
      report of any cardiovascular or pulmonary symptom. CONCLUSIONS: Cardiovascular
      and pulmonary symptoms are common among Chinese older adults in the U.S. Future
      longitudinal research is needed to examine changes in Chinese older adults'
      burden of cardiopulmonary symptoms and their health and well-being.

PMID- 25378448
TI  - Trust in physicians among U.S. chinese older adults.
AB  - BACKGROUND: Trust in physicians influences the health and well-being of older
      adults and is an important indicator to assess the quality of medical care.
      However, Asian aging populations are often underrepresented in studies of patient
      trust in physicians. This study aims to examine the level of trust in physicians
      among Chinese older adults in a community-dwelling Chinese aging population.
      METHODS: Data were drawn from the Population Study of Chinese Elderly, a
      population-based survey of U.S. Chinese older adults in the Greater Chicago area.
      Guided by a community-based participatory research approach, a total of 3,159
      Chinese older adults aged 60 and above were surveyed. An 11-item scale was used
      to measure participants' trust in physicians. RESULTS: On a scale of 11-55, the
      level of trust in physician among U.S. Chinese older adults was 42.0 (SD = 6.3).
      Items related to confidence in physicians' knowledge and skills were most
      commonly endorsed, including trusting physicians' judgment on medical care
      (84.8%), trusting physicians' advice (84.2%), and trusting physicians' words that
      something is so and must be true (81.2%). Younger age, male gender, higher
      educational level, fewer years of residing in the United States and in the
      community, poorer self-reported health status, and poorer quality of life were
      associated with lower level of trust in physicians. CONCLUSIONS: Trust in
      physician is commonly endorsed among U.S. Chinese older adults. However, future
      longitudinal studies are needed to improve our understanding of risk factors and
      outcomes associated with trust in physicians among U.S. Chinese older adults.

PMID- 25378449
TI  - Levels of health literacy in a community-dwelling population of Chinese older
      adults.
AB  - BACKGROUND: Lower levels of health literacy have been associated with adverse
      health outcomes, especially for older adults. However, limited research has been
      conducted to understand health literacy levels among Chinese American older
      adults. METHODS: The PINE study is an epidemiological cohort of 3,159 community
      dwelling Chinese older adults, 95% of whom do not speak or read English. Chinese
      older adults' health literacy levels were examined using the Chinese version of
      the Rapid Estimate of Adult Literacy in Medicine, Revised (REALM-R) test. Kruskal
      Wallis test and chi-square statistics were used to identify significant
      differences by sociodemographic and self-reported health characteristics. Pearson
      and Spearman correlation coefficients were used to examine correlations between
      personal characteristics and health literacy level. RESULTS: The mean age among
      this sample of Chinese older adults was 72.8 years (SD = 8.3, range = 60-105) and
      the mean REALM-R test score was 6.9 [SD = 2.3, range (0-8)]. Health literacy was
      positively associated with education, marriage status, and number of people
      living with. Older age, being female, greater number of children, years in the
      United States, and preference for speaking Cantonese or Taishanese were
      negatively associated with health literacy. Health literary was not associated
      with self-reported health status or quality of life. CONCLUSIONS: In this Chicago
      Chinese population, older adults had reasonable levels of health literacy in
      Chinese. Future longitudinal research is needed to understand risk/protective
      factors associated with health literacy level in Chinese older adults.

PMID- 25378450
TI  - Anxiety among community-dwelling U.S. Chinese older adults.
AB  - BACKGROUND: This study aimed to explore the prevalence and correlates of anxiety
      disorders and any anxiety symptoms among community-dwelling U.S. Chinese older
      adults. METHODS: Guided by a community-based participatory research approach,
      3,159 community-dwelling Chinese older adults in the Greater Chicago area were
      interviewed in person between 2011 and 2013. RESULTS: Of 3,159 older adults
      surveyed, 8.5% had anxiety disorders and 65.0% reported having any anxiety
      symptoms. Being female, unmarried, poorer health status, lower quality of life,
      and worsening health over the past year were positively correlated with anxiety
      disorders and any anxiety symptoms. Living with fewer people and having fewer
      children were only correlated with any anxiety symptoms and lower income was only
      correlated with anxiety disorders. CONCLUSIONS: This study emphasizes that
      interventions for anxiety among Chinese older adults should give special
      attention to older women, those who are unmarried, with impaired health status,
      and poorer quality of life. Further longitudinal studies should be conducted to
      better understand risk factors and outcomes associated with anxiety among U.S.
      Chinese older adults.

PMID- 25378451
TI  - Do the definitions of elder mistreatment subtypes matter? Findings from the PINE
      Study.
AB  - BACKGROUND: Elder mistreatment (EM) is a pervasive public health issue and is
      associated with morbidity and premature mortality. This study aimed to examine
      how the prevalence of EM and its subtypes vary using different definitions among
      U.S. Chinese older adults. METHODS: The Population Study of Chinese Elderly in
      Chicago is a population-based epidemiological survey of 3,159 U.S. Chinese older
      adults in the Greater Chicago area that is guided by a community-based
      participatory research approach. Participants answered questions regarding
      psychological, physical, and sexual abuse, caregiver neglect, and financial
      exploitation. Definitional approaches for EM and its subtypes were constructed
      from least restrictive to most restrictive. RESULTS: Using different definitional
      criteria, the prevalence of psychological abuse was 1.1%-9.8%, physical abuse was
      1.1%, sexual abuse was 0.2%, caregiver neglect was 4.6%-11.1%, and financial
      exploitation was 8.8%-9.3%. Overall, EM varied from 13.9% to 25.8%, depending on
      the defining criteria. Regardless of the definition used, those who experienced
      EM were more likely to be older and have higher educational attainment, poor
      health status, poor quality of life, and worsened health change in the last year.
      However, among the different definitions of overall EM, there were no
      statistically significant differences across sociodemographic characteristics or
      self-reported health status associated with EM criteria. CONCLUSIONS: Elder
      mistreatment is prevalent among U.S. Chinese older adults regardless of the
      definitional criteria. Sociodemographic characteristics associated with EM did
      not differ by definitional criteria. Future longitudinal studies are needed to
      quantify the risk and protective factors associated with EM in Chinese aging
      populations.

PMID- 25378452
TI  - Preventive care service usage among Chinese older adults in the Greater Chicago
      area.
AB  - BACKGROUND: Preventive care is important for reducing morbidity and mortality
      among the elderly, but racial/ethnic disparities exist in use of preventive care
      services. We aimed to develop a better understanding of preventive care service
      utilization among Chinese older adults in the Greater Chicago area. METHODS: We
      used data collected from the Population Study of Chinese Elderly in Chicago
      study, a population-based survey of 3,159 community-dwelling Chinese older adults
      in the Greater Chicago area. Preventive care services assessed include use of
      flu, pneumonia, and hepatitis B vaccines as well as colon, breast, cervical and
      prostate cancer screening. We also examined sociodemographic, health and quality
      of life correlates for preventive care service use. RESULTS: We found that
      although Chinese older adults had lower utilization rates for the pneumonia
      vaccine and cancer screening, their utilization of the flu shot was consistent
      with national utilization rates. No sociodemographic, self-reported health, or
      quality of life characteristics were associated with all nine of the preventive
      care services. CONCLUSION: Use of preventive care services except flu vaccination
      was low among Chinese older adults in the Greater Chicago area. However, future
      longitudinal studies may be necessary to further elucidate preventive care
      service utilization patterns among Chinese older adults.

PMID- 25378453
TI  - Social engagement among U.S. Chinese older adults--findings from the PINE Study.
AB  - BACKGROUND: Social engagement is a key indicator of older adults' later life
      quality and health status, but few studies have comprehensively examined social
      engagement patterns of U.S. Chinese older adults. This study assesses social
      engagement patterns among U.S. Chinese older adults. METHODS: Data were collected
      by the Population Study of Chinese Elderly project, a cross-sectional population
      based study of 3,159 U.S. Chinese older adults aged 60 and older in the greater
      Chicago area. Social engagement patterns were examined with a list of 16 social
      engagement activity related questions. Analysis of variance and Pearson or
      Spearman correlation coefficients were used to examine correlations between
      sociodemographic and health characteristics and social engagement. RESULTS: Age
      was negatively associated with social engagement actives for Chinese older
      adults. Although education had a significant positive correlation on older
      adults' participation in social engagement activities, income did not show any
      significant correlation. Perceived health status and quality of life were also
      positively correlated with social engagement. Chinese older adults were more
      likely to visit community centers than any other social or cultural venues.
      CONCLUSIONS: This study highlights the important role community centers play in
      the lives of Chinese older adults. Further, longitudinal studies are also
      necessary to understand the predictors and outcomes of social engagement levels
      among Chinese older adults.

PMID- 25378454
TI  - The association between filial piety and suicidal ideation: findings from a
      community-dwelling Chinese aging population.
AB  - BACKGROUND: Suicidal ideation is a public health issue that has a significant
      impact at the individual, family, community, and societal levels. This study
      aimed to examine the association between filial piety and suicidal ideation among
      U.S. Chinese older adults. METHODS: Guided by a community-based participatory
      research approach, 3,159 community-dwelling Chinese older adults in the Greater
      Chicago area were interviewed in person between 2011 and 2013. Independent
      variables were expectations and receipt of filial piety from the older adult's
      perspective. Dependent variables were suicidal ideation in the last 2 weeks and
      last 12 months. Logistic regression analyses were performed. RESULTS: Of the
      3,159 participants interviewed, 58.9% were female and the mean age was 72.8
      years. After adjusting for age, sex, education, income, medical comorbidities,
      and depressive symptoms, lower receipt of filial piety was associated with
      increased risk for 2-week suicidal ideation (odds ratio: 1.07, 95% confidence
      interval: 1.03-1.11) and 12-month suicidal ideation (odds ratio: 1.07, 95%
      confidence interval: 1.04-1.11). The lowest tertiles of filial piety receipt was
      associated with greater risk for 2-week suicidal ideation (odds ratio: 1.95, 95%
      confidence interval: 1.12-3.38) and 12-month suicidal ideation (odds ratio: 2.17,
      95% confidence interval: 1.35-3.48). However, no statistically significant
      associations were found between overall filial piety expectations and suicidal
      ideation in the last 2 weeks or in the last 12 months. DISCUSSION: This study
      suggests that filial piety receipt is an important risk factor for suicidal
      ideation among U.S. Chinese older adults. Future longitudinal studies are needed
      to quantify the temporal association between filial piety and suicidal ideation.

PMID- 25378455
TI  - Nurturing empathy: an oncologist looks at medicine and himself.

PMID- 25378456
TI  - A phase II trial of capecitabine concomitantly with whole-brain radiotherapy
      followed by capecitabine and sunitinib for brain metastases from breast cancer.
AB  - BACKGROUND: Brain metastasis from breast cancer presents a significant threat to
      women's health and quality of life. Capecitabine and sunitinib have shown some
      activity in this setting; therefore, we conducted a single-arm phase II trial
      with these agents. METHODS: Patients with breast cancer and central nervous
      system (CNS) metastases received whole-brain radiotherapy concurrently with
      capecitabine (1,000 mg/m(2) per day for 14 consecutive days), followed by
      concomitant capecitabine (2,000 mg/m(2) per day for 2 weeks followed by a 1-week
      break) and sunitinib (37.5 mg daily, continuously). The primary endpoint was
      progression-free survival (PFS). RESULTS: Of 25 planned patients that would be
      required to detect a 4-month improvement (from 5 to 9 months) in median PFS with
      80% power, 12 were enrolled, and the study was then closed for slow accrual.
      Median PFS was 4.7 months, and median overall survival was 10 months. In the CNS,
      25% had progressive disease, and 83% experienced extra-CNS progression. The most
      common side effects were fatigue and nausea. CONCLUSION: In 12 evaluable patients
      studied, concurrent capecitabine and whole-brain radiation followed by
      capecitabine and sunitinib did not extend PFS over historical rates and was
      associated with significant toxicity. Our study was small and closed due to slow
      accrual.

PMID- 25378457
TI  - Carpal tunnel syndrome.

PMID- 25378458
TI  - Successful detection and genotyping of rubella virus from preserved umbilical
      cord of patients with congenital rubella syndrome.

PMID- 25378460
TI  - Emerging Escherichia coli O25b/ST131 clone predicts treatment failure in urinary
      tract infections.
AB  - BACKGROUND: We described the clinical predictive role of emerging Escherichia
      coli O25b/sequence type 131 (ST131) in treatment failure of urinary tract
      infection. METHODS: In this prospective observational cohort study, the
      outpatients with acute cystitis with isolation of E. coli in their urine cultures
      were assessed. All the patients were followed up for clinical cure after 10 days
      of treatment. Detection of the E. coli O25:H4/ST131 clone was performed by
      multiplex polymerase chain reaction (PCR) for phylogroup typing and using PCR
      with primers for O25b rfb and allele 3 of the pabB gene. RESULTS: In a cohort of
      patients with diagnosis of acute urinary cystitis, 294 patients whose urine
      cultures were positive with a growth of >10(4) colony-forming units/mL of E. coli
      were included in the study. In empiric therapy, ciprofloxacin was the first
      choice of drug (27%), followed by phosphomycin (23%), trimethoprim
      sulfamethoxazole (TMP-SMX) (9%), and cefuroxime (7%). The resistance rate was 39%
      against ciprofloxacin, 44% against TMP-SMX, and 25% against cefuroxime. Thirty
      five of 294 (12%) isolates were typed under the O25/ST131 clone. The clinical
      cure rate was 85% after the treatment. In multivariate analysis, detection of the
      O25/ST131 clone (odds ratio [OR], 4; 95% confidence interval [CI], 1.51-10.93; P
      = .005) and diabetes mellitus (OR, 2.1; 95% CI, .99-4.79; P = .05) were found to
      be significant risk factors for the treatment failure. In another multivariate
      analysis performed among quinolone-resistant isolates, treatment failure was 3
      times more common among the patients who were infected with ST131 E. coli (OR, 3;
      95% CI, 1.27-7.4; P = .012). CONCLUSIONS: In urinary tract infections, the E.
      coli ST131 clone seems to be a consistent predictor of treatment failure.

PMID- 25378459
TI  - Influence of virulence genotype and resistance profile in the mortality of
      Pseudomonas aeruginosa bloodstream infections.
AB  - BACKGROUND: The type III secretion system (TTSS) is a major virulence determinant
      of Pseudomonas aeruginosa. The objective of this study was to determine whether
      the TTSS genotype is a useful prognostic marker of P. aeruginosa bacteremia
      mortality. We also studied the potential association between TTSS genotypes and
      multidrug-resistant (MDR) profiles, and how this interaction impacts the outcome
      of bloodstream infections. METHODS: We performed a post hoc analysis of a
      published prospective multicenter cohort of P. aeruginosa bloodstream infections.
      The impact in mortality of TTSS genotypes (exoS, exoT, exoU, and exoY genes) and
      resistance profiles was investigated. Cox regression analysis was used to control
      for confounding variables. RESULTS: Among 590 patients, the 30-day mortality rate
      was 30% (175 patients), and 53% of them died in the first 5 days (early
      mortality). The unadjusted probabilities of survival until 5 days was 31.4% (95%
      confidence interval [CI], 17.4%-49.4%) for the patients with exoU-positive
      isolates and 53.2% (95% CI, 44.6%-61.5%) for exoU-negative isolates (log rank P =
      .005). After adjustment for confounders, exoU genotype (adjusted hazard ratio
      [aHR], 1.90 [95% CI, 1.15-3.14]; P = .01) showed association with early
      mortality. In contrast, late (30-day) mortality was not influenced by TTSS
      genotype but was independently associated with MDR profiles (aHR,1.40 [95% CI,
      1.01-1.94]; P = .04). Moreover, the exoU genotype (21% of all isolates) was
      significantly less frequent (13%) among MDR strains (particularly among
      extensively drug-resistant isolates, 5%), but was positively linked to moderately
      resistant (1-2 antipseudomonals) phenotypes (34%). CONCLUSIONS: Our results
      indicate that the exoU genotype, which is associated with specific susceptibility
      profiles, is a relevant independent marker of early mortality in P. aeruginosa
      bacteremia.

PMID- 25378463
TI  - Mitochondria. Cell cycle-dependent regulation of mitochondrial preprotein
      translocase.
AB  - Mitochondria play central roles in cellular energy conversion, metabolism, and
      apoptosis. Mitochondria import more than 1000 different proteins from the
      cytosol. It is unknown if the mitochondrial protein import machinery is connected
      to the cell division cycle. We found that the cyclin-dependent kinase Cdk1
      stimulated assembly of the main mitochondrial entry gate, the translocase of the
      outer membrane (TOM), in mitosis. The molecular mechanism involved
      phosphorylation of the cytosolic precursor of Tom6 by cyclin Clb3-activated Cdk1,
      leading to enhanced import of Tom6 into mitochondria. Tom6 phosphorylation
      promoted assembly of the protein import channel Tom40 and import of fusion
      proteins, thus stimulating the respiratory activity of mitochondria in mitosis.
      Tom6 phosphorylation provides a direct means for regulating mitochondrial
      biogenesis and activity in a cell cycle-specific manner. 

PMID- 25378462
TI  - Paleogenomics. Genomic structure in Europeans dating back at least 36,200 years.
AB  - The origin of contemporary Europeans remains contentious. We obtained a genome
      sequence from Kostenki 14 in European Russia dating from 38,700 to 36,200 years
      ago, one of the oldest fossils of anatomically modern humans from Europe. We find
      that Kostenki 14 shares a close ancestry with the 24,000-year-old Mal'ta boy from
      central Siberia, European Mesolithic hunter-gatherers, some contemporary western
      Siberians, and many Europeans, but not eastern Asians. Additionally, the Kostenki
      14 genome shows evidence of shared ancestry with a population basal to all
      Eurasians that also relates to later European Neolithic farmers. We find that
      Kostenki 14 contains more Neandertal DNA that is contained in longer tracts than
      present Europeans. Our findings reveal the timing of divergence of western
      Eurasians and East Asians to be more than 36,200 years ago and that European
      genomic structure today dates back to the Upper Paleolithic and derives from a
      metapopulation that at times stretched from Europe to central Asia. 

PMID- 25378461
TI  - Black hole physics. Black hole lightning due to particle acceleration at
      subhorizon scales.
AB  - Supermassive black holes with masses of millions to billions of solar masses are
      commonly found in the centers of galaxies. Astronomers seek to image jet
      formation using radio interferometry but still suffer from insufficient angular
      resolution. An alternative method to resolve small structures is to measure the
      time variability of their emission. Here we report on gamma-ray observations of
      the radio galaxy IC 310 obtained with the MAGIC (Major Atmospheric Gamma-ray
      Imaging Cherenkov) telescopes, revealing variability with doubling time scales
      faster than 4.8 min. Causality constrains the size of the emission region to be
      smaller than 20% of the gravitational radius of its central black hole. We
      suggest that the emission is associated with pulsar-like particle acceleration by
      the electric field across a magnetospheric gap at the base of the radio jet. 

PMID- 25378464
TI  - Development of Six Arts, a Culturally Appropriate Multimodal Nonpharmacological
      Intervention in Dementia.
AB  - PURPOSE: There is accumulating evidence for the efficacy of nonpharmacological
      multimodal stimulation interventions in maintaining cognition and improving
      quality of life in people with mild-to-moderate dementia. However, the complex
      nature of these interventions limits their application in practice and research.
      We report here the design and development of a culturally appropriate framework,
      the Six Arts, to guide delivery of multimodal interventions in a Chinese
      community. DESIGN AND DEVELOPMENT: The Six Arts are a core set of Confucian
      philosophy comprising 6 disciplines of rites, music, archery, charioteering,
      literacy, and numeracy. They correspond to major mind-body functional domains of
      social functioning; music and rhythm; visuospatial and fine motor skills;
      kinesthetic and gross motor skills; language and verbal skills; and executive
      function. Using Six Arts as a framework, we mapped theoretical principles and
      evidence-based nonpharmacological interventions of cognitive stimulation,
      physical exercise, and social activities against the 6 functional domains. From
      2011, we field-tested the use of Six Arts in structuring intervention programs in
      263 people in a dementia day center in Hong Kong. RESULTS: The Six Arts was
      operationalized through the development of an intervention activity database, a
      scoring system for intensity level, and a service delivery model for application
      in dementia day centers. IMPLICATIONS: Six Arts can be used as framework for
      structuring nonpharmacological group intervention programs in dementia day center
      in a metropolitan Chinese city. Its cultural appropriateness may facilitate
      communication and shared decision making with families with dementia in
      communities influenced by Confucian philosophy.

PMID- 25378465
TI  - The INTERACT Institute: Observations on Dissemination of the INTERACT Quality
      Improvement Program Using Certified INTERACT Trainers.
AB  - Unnecessary hospitalizations of vulnerable nursing home (NH) residents can lead
      to hospital-acquired conditions, morbidity, mortality, and excess health care
      expenditures. Previous research has shown that a substantial percentage of these
      hospitalizations are preventable. Interventions to reduce acute care transfers
      (INTERACT) is a quality improvement program that has been adopted by many NHs
      throughout the United States. The original INTERACT toolkit was first created in
      a project supported by the Centers for Medicare and Medicaid Services. The
      toolkit was further refined and tested in a collaborative quality improvement
      project involving 30 NHs in 3 states, which resulted in a 17% reduction in all
      cause hospitalizations. This study was limited because it was not randomized or
      controlled. Nevertheless, the data provide evidence that the program, even in the
      absence of strong regulatory oversight or financial incentives, is feasible to
      implement and that more active program engagement is associated with higher
      reductions in hospitalization. This paper describes dissemination of the INTERACT
      program using a pragmatic and relatively low cost model to prepare certified
      INTERACT Trainers in collaboration with several professional organizations. 

PMID- 25378466
TI  - flowDensity: reproducing manual gating of flow cytometry data by automated
      density-based cell population identification.
AB  - SUMMARY: flowDensity facilitates reproducible, high-throughput analysis of flow
      cytometry data by automating a predefined manual gating approach. The algorithm
      is based on a sequential bivariate gating approach that generates a set of
      predefined cell populations. It chooses the best cut-off for individual markers
      using characteristics of the density distribution. The Supplementary Material is
      linked to the online version of the manuscript. AVAILABILITY AND IMPLEMENTATION:
      R source code freely available through BioConductor
      (http://master.bioconductor.org/packages/devel/bioc/html/flowDensity.html.). Data
      available from FlowRepository.org (dataset FR-FCM-ZZBW). CONTACT:
      rbrinkman@bccrc.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 25378468
TI  - Mechanisms and clinical significance of adenosine-induced dormant accessory
      pathway conduction after catheter ablation.
AB  - BACKGROUND: Adenosine can unmask dormant pulmonary vein conduction after
      isolation. The role of adenosine in uncovering dormant accessory pathway (AP)
      conduction after AP ablation is unknown. METHODS AND RESULTS: We evaluated 109
      consecutive patients (age, 41 +/- 28 years; 62 [57%] men) who were administered
      adenosine after successful AP ablation. Dormant AP conduction was defined as
      adenosine-induced recurrent AP conduction, as demonstrated by recurrent
      preexcitation or change in retrograde ventriculoatrial activation patterns.
      Dormant AP conduction was identified in 13 (12%) patients. Adenosine led to
      transient retrograde AP conduction in 6 patients and transient anterograde AP
      conduction in 8 patients. In all these cases, adenosine-induced AP conduction
      occurred during the bradycardia phase of adenosine effect and resulted in dormant
      AP conduction times shorter than atrioventricular nodal conduction times before
      adenosine administration. On the basis of analysis of timing of occurrence of
      dormant AP conduction, the mechanism of adenosine-induced AP conduction was
      determined to be caused by AP excitability recovery in >= 12 (92%) cases. The
      presence of dormant AP conduction was a significant predictor of chronic
      recurrent AP conduction requiring repeat ablation (odds ratio, 8.54; 95%
      confidence interval, 1.09-66.9; P=0.041). CONCLUSIONS: Adenosine can unmask
      dormant AP conduction after catheter ablation. Direct effects of adenosine on the
      AP, possibly via AP membrane potential hyperpolarization, are the dominant
      mechanism of adenosine-induced AP conduction after ablation. Dormant AP
      conduction is associated with higher rates of recurrent AP conduction requiring
      repeat ablation.

PMID- 25378469
TI  - Idiopathic accelerated idioventricular rhythm or ventricular tachycardia
      originating from the right bundle branch: unusual type of ventricular arrhythmia.
AB  - BACKGROUND: Accelerated idioventricular rhythm (AIVR) or ventricular tachycardia
      (VT) originating from the right bundle branch (RBB) is rare and published
      clinical data on such arrhythmia are scarce. In this study, we will describe the
      clinical manifestations, diagnosis, and management of a cohort of patients with
      this novel arrhythmia. METHODS AND RESULTS: Eight patients (5 men; median age, 25
      years) with RBB-AIVR/VT were consecutively enrolled in the study. Pharmacological
      testing, exercise treadmill testing, electrophysiological study, and catheter
      ablation were performed in the study patients, and ECG features were
      characterized. All RBB-AIVR/VTs were of typical left bundle-branch block
      morphology with atrioventricular dissociation. The arrhythmias, which
      demonstrated chronotropic variability, were often isorhythmic with sinus rhythm
      and were accelerated by physical exercise, stress, and intravenous isoprenaline
      infusion. The rate of RBB-AIVR/VT varied from 45 to 200 beats per minute. Two
      patients experienced syncope, and 3 had impaired left ventricular function.
      Metoprolol was proven to be the most effective drug to decelerate the arrhythmia
      rate and relieve symptoms. Electrophysiology study was performed in 5 patients
      and the earliest activation with a sharp RBB potential was localized in the mid
      or distal RBB area. Catheter ablation terminated the arrhythmia with subsequent
      RBB block morphology during sinus rhythm. During follow-up, patients' symptoms
      were controlled with normalization of left ventricular function either on
      metoprolol or by catheter ablation. CONCLUSIONS: RBB-AIVR/VT is an unusual type
      of ventricular arrhythmia. It can result in significant symptoms and depressed
      ventricular function and can be successfully treated with catheter ablation.

PMID- 25378470
TI  - The use of echocardiography in acute cardiovascular care: recommendations of the
      European Association of Cardiovascular Imaging and the Acute Cardiovascular Care
      Association.
AB  - Echocardiography is one of the most powerful diagnostic and monitoring tools
      available to the modern emergency/ critical care practitioner. Currently, there
      is a lack of specific European Association of Cardiovascular Imaging/Acute
      Cardiovascular Care Association recommendations for the use of echocardiography
      in acute cardiovascular care. In this document, we describe the practical
      applications of echocardiography in patients with acute cardiac conditions, in
      particular with acute chest pain, acute heart failure, suspected cardiac
      tamponade, complications of myocardial infarction, acute valvular heart disease
      including endocarditis, acute disease of the ascending aorta and post
      intervention complications. Specific issues regarding echocardiography in other
      acute cardiovascular care scenarios are also described. 

PMID- 25378471
TI  - Dynamic perfusion CT: what is normal myocardial blood flow?

PMID- 25378472
TI  - Dynamic CT myocardial perfusion measurements of resting and hyperaemic blood flow
      in low-risk subjects with 128-slice dual-source CT.
AB  - AIMS: The aim of the study was to measure rest and stress myocardial blood flow
      (MBF) values prospectively in a low-risk population with 128-slice dual-source
      computed tomography (CT) and to compare MBF/coronary flow reserve (CFR) values to
      that of a second population with a documented coronary artery disease (CAD).
      METHODS AND RESULTS: This study evaluates resting and hyperaemic MBF in 35 low
      risk individuals identified by the modified Framingham Risk score and a calcium
      score of <100. The patients were scanned using 80 kV and quantitative blood flow
      values were generated using complete time-attenuation curves. Global resting and
      hyperaemic MBF was 74.08 +/- 16.30 and 135.24 +/- 28.89 mL/100 g/min,
      respectively, with CFR of 1.86 +/- 0.38. Resting MBF was 76.98 +/- 25.68, 66.98
      +/- 19.66, 81.34 +/- 21.40, and 63.35 +/- 16.35 mL/100 g/min in anterior, septal,
      lateral, and inferior walls, respectively, and corresponding hyperaemic MBF was
      133.25 +/- 29.80, 123.47 +/- 31.03, 148.60 +/- 32.69, and 124.21 +/- 31.54 mL/100
      g/min, respectively. In the population with CAD, global resting and hyperaemic
      MBF were 82.29 +/- 16.87 and 81.98 +/- 18.54 mL/100 g/min and 107.95 +/- 25.25
      and 106.93 +/- 32.91 mL/100 g/min in the group with ischaemia only and infarction
      only, respectively, with corresponding CFR of 1.33 +/- 0.27 and 1.33 +/- 0.46,
      respectively (statistically different from the low-risk population). Radiation
      dose for CT myocardial perfusion imaging (CTMPI) was 6.72 +/- 2.71 and 6.19 +/-
      2.19 mSv for stress and rest scans, respectively. This was 30% lower than a
      radiation dose in the scanning historical cohort at 100 kV. There was no
      significant difference in the signal-to-noise ratio and contrast-to-noise ratio
      between low-risk cohort and historical cohort scanned at 80 and 100 kV,
      respectively. CONCLUSIONS: Baseline, hyperaemic MBF and CFR values in a low-risk
      cohort can be evaluated with dynamic myocardial perfusion imaging using 80 kV.

PMID- 25378473
TI  - In silico scrutiny of genes revealing phylogenetic congruence with clinical
      prevalence or tropism properties of Chlamydia trachomatis strains.
AB  - Microbes possess a multiplicity of virulence factors that confer them the ability
      to specifically infect distinct biological niches. Contrary to what is known for
      other bacteria, for the obligate intracellular human pathogen Chlamydia
      trachomatis, the knowledge of the molecular basis underlying serovars' tissue
      specificity is scarce. We examined all ~900 genes to evaluate the association
      between individual phylogenies and cell-appetence or ecological success of C.
      trachomatis strains. Only ~1% of the genes presented a tree topology showing the
      segregation of all three disease groups (ocular, urogenital, and lymphatic) into
      three well-supported clades. Approximately 28% of the genes, which include the
      majority of the genes encoding putative type III secretion system effectors and
      Inc proteins, present a phylogenetic tree where only lymphogranuloma venereum
      strains form a clade. Similarly, an exclusive phylogenetic segregation of the
      most prevalent genital serovars was observed for 61 proteins. Curiously, these
      serovars are phylogenetically cosegregated with the lymphogranuloma venereum
      serovars for ~20% of the genes. Some clade-specific pseudogenes were identified
      (novel findings include the conserved hypothetical protein CT037 and the
      predicted alpha-hemolysin CT473), suggesting their putative expendability for the
      infection of particular niches. Approximately 3.5% of the genes revealed a
      significant overrepresentation of nonsynonymous mutations, and the majority
      encode proteins that directly interact with the host. Overall, this in silico
      scrutiny of genes whose phylogeny is congruent with clinical prevalence or tissue
      specificity of C. trachomatis strains may constitute an important database of
      putative targets for future functional studies to evaluate their biological role
      in chlamydial infections. 

PMID- 25378474
TI  - A Shigella flexneri virulence plasmid encoded factor controls production of outer
      membrane vesicles.
AB  - Shigella spp. use a repertoire of virulence plasmid-encoded factors to cause
      shigellosis. These include components of a Type III Secretion Apparatus (T3SA)
      that is required for invasion of epithelial cells and many genes of unknown
      function. We constructed an array of 99 deletion mutants comprising all genes
      encoded by the virulence plasmid (excluding those known to be required for
      plasmid maintenance) of Shigella flexneri. We screened these mutants for their
      ability to bind the dye Congo red: an indicator of T3SA function. This screen
      focused our attention on an operon encoding genes that modify the cell envelope
      including virK, a gene of partially characterized function. We discovered that
      virK is required for controlled release of proteins to the culture supernatant.
      Mutations in virK result in a temperature-dependent overproduction of outer
      membrane vesicles (OMVs). The periplasmic chaperone/protease DegP, a known
      regulator of OMV production in Escherichia coli (encoded by a chromosomal gene),
      was found to similarly control OMV production in S. flexneri. Both virK and degP
      show genetic interactions with mxiD, a structural component of the T3SA. Our
      results are consistent with a model in which VirK and DegP relieve the
      periplasmic stress that accompanies assembly of the T3SA. 

PMID- 25378476
TI  - Correcting for sequencing error in maximum likelihood phylogeny inference.
AB  - Accurate phylogenies are critical to taxonomy as well as studies of speciation
      processes and other evolutionary patterns. Accurate branch lengths in phylogenies
      are critical for dating and rate measurements. Such accuracy may be jeopardized
      by unacknowledged sequencing error. We use simulated data to test a correction
      for DNA sequencing error in maximum likelihood phylogeny inference. Over a wide
      range of data polymorphism and true error rate, we found that correcting for
      sequencing error improves recovery of the branch lengths, even if the assumed
      error rate is up to twice the true error rate. Low error rates have little effect
      on recovery of the topology. When error is high, correction improves topological
      inference; however, when error is extremely high, using an assumed error rate
      greater than the true error rate leads to poor recovery of both topology and
      branch lengths. The error correction approach tested here was proposed in 2004
      but has not been widely used, perhaps because researchers do not want to commit
      to an estimate of the error rate. This study shows that correction with an
      approximate error rate is generally preferable to ignoring the issue. 

PMID- 25378475
TI  - Regulation of synaptic transmission at the Caenorhabditis elegans M4
      neuromuscular junction by an antagonistic relationship between two calcium
      channels.
AB  - In wild-type Caenorhabditis elegans, the synapse from motor neuron M4 to
      pharyngeal terminal bulb (TB) muscles is silent, and the muscles are instead
      excited by gap junction connections from adjacent muscles. An eat-5 innexin
      mutant lacking this electrical connection has few TB contractions and is unable
      to grow well on certain foods. We showed previously that this defect can be
      overcome by activation of the M4 -> TB synapse. To identify genes that negatively
      regulate synaptic transmission, we isolated new suppressors of eat-5. To our
      surprise, these suppressors included null mutations in NPQR-type calcium channel
      subunit genes unc-2 and unc-36. Our results are consistent with the hypothesis
      that Ca(2+) entry through the NPQR-type channel inhibits synaptic transmission by
      activating the calcium-activated K(+) channel SLO-1, thus antagonizing the EGL-19
      L-type calcium channel. 

PMID- 25378467
TI  - Interaction between digoxin and dronedarone in the PALLAS trial.
AB  - BACKGROUND: Elevated serum digoxin concentration can cause toxicity, including
      death. Dronedarone increases digoxin concentration by P-glycoprotein interaction.
      In Permanent Atrial Fibrillation Outcome Study Using Dronedarone On Top Of
      Standard Therapy Trial (PALLAS), dronedarone was associated with both increased
      cardiovascular death and heart failure in patients with permanent atrial
      fibrillation. The present analysis examines whether the dronedarone-digoxin
      interaction might explain these adverse outcomes. METHODS AND RESULTS: Subgroup
      analysis was performed to compare outcomes of patients on digoxin at baseline or
      not. In PALLAS, 1619 patients were randomized to dronedarone and 1617 to placebo,
      of whom 544 (33.6%) and 526 (32.5%) were receiving digoxin, respectively. Median
      (Q1,Q3) digoxin serum concentration on day 7 was 1.1 (0.7,1.5) ng/mL on
      dronedarone and 0.7 (0.5,1.1) ng/mL on placebo (P<0.001). Among patients on
      digoxin, there were 15 (8.6%/year) cardiovascular deaths on dronedarone and 2
      (1.2%/year) on placebo (adjusted hazard ratio, 7.31; 95% confidence interval,
      1.66-32.20; P=0.009). Among patients not on digoxin, there were 6 cardiovascular
      deaths on dronedarone (1.7%/year) and 8 on placebo (2.2%/year; adjusted hazard
      ratio, 0.67; 95% confidence interval, 0.23-1.95; P=0.46; interaction P value
      0.01). In patients on digoxin, there were 11 arrhythmic deaths on dronedarone and
      none on placebo; and in patients not on digoxin, there were 2 arrhythmic deaths
      on dronedarone and 4 on placebo (P value for interaction 0.002). There was no
      interaction between baseline digoxin use and the adverse effect of dronedarone on
      heart failure events. CONCLUSIONS: In PALLAS, there was a strong effect of
      concurrent digoxin use on the adverse effect of dronedarone on cardiovascular
      death, but not on occurrence of heart failure. CLINICAL TRIAL REGISTRATION:
      http://www.clinicaltrials.gov. Unique identifier: NCT01151137.

PMID- 25378477
TI  - Differential retrotranslocation of mitochondrial Bax and Bak.
AB  - The Bcl-2 proteins Bax and Bak can permeabilize the outer mitochondrial membrane
      and commit cells to apoptosis. Pro-survival Bcl-2 proteins control Bax by
      constant retrotranslocation into the cytosol of healthy cells. The stabilization
      of cytosolic Bax raises the question whether the functionally redundant but
      largely mitochondrial Bak shares this level of regulation. Here we report that
      Bak is retrotranslocated from the mitochondria by pro-survival Bcl-2 proteins.
      Bak is present in the cytosol of human cells and tissues, but low shuttling rates
      cause predominant mitochondrial Bak localization. Interchanging the membrane
      anchors of Bax and Bak reverses their subcellular localization compared to the
      wild-type proteins. Strikingly, the reduction of Bax shuttling to the level of
      Bak retrotranslocation results in full Bax toxicity even in absence of apoptosis
      induction. Thus, fast Bax retrotranslocation is required to protect cells from
      commitment to programmed death. 

PMID- 25378479
TI  - Suppressing nonsense--a surprising function for 5-azacytidine.
AB  - In this issue of EMBO Molecular Medicine, Bhuvanagiri et al report on a chemical
      means to convert molecular junk into gold. They identify a chemical inhibitor of
      a quality control pathway that is best known for its ability to clear cells of
      rubbish, but that in certain cases can be detrimental because it eliminates
      "useful" garbage. The chemical inhibitor identified by Bhuvanagiri et al perturbs
      Nonsense-Mediated RNA Decay (NMD), a RNA surveillance pathway that targets mRNAs
      harboring premature termination codons (PTCs) for degradation (Kervestin &
      Jacobson, 2012).

PMID- 25378478
TI  - The mammalian tRNA ligase complex mediates splicing of XBP1 mRNA and controls
      antibody secretion in plasma cells.
AB  - The unfolded protein response (UPR) is a conserved stress-signaling pathway
      activated after accumulation of unfolded proteins within the endoplasmic
      reticulum (ER). Active UPR signaling leads to unconventional, enzymatic splicing
      of XBP1 mRNA enabling expression of the transcription factor XBP1s to control ER
      homeostasis. While IRE1 has been identified as the endoribonuclease required for
      cleavage of this mRNA, the corresponding ligase in mammalian cells has remained
      elusive. Here, we report that RTCB, the catalytic subunit of the tRNA ligase
      complex, and its co-factor archease mediate XBP1 mRNA splicing both in vitro and
      in vivo. Depletion of RTCB in plasma cells of Rtcb(fl/fl) Cd23-Cre mice prevents
      XBP1s expression, which normally is strongly induced during plasma cell
      development. RTCB-depleted plasma cells show reduced and disorganized ER
      structures as well as severe defects in antibody secretion. Targeting RTCB and/or
      archease thus represents a promising strategy for the treatment of a growing
      number of diseases associated with elevated expression of XBP1s. 

PMID- 25378481
TI  - Brown is the new green: brownfield sites often harbour a surprisingly large
      amount of biodiversity.

PMID- 25378480
TI  - De novo design of a trans-beta-N-acetylglucosaminidase activity from a GH1 beta
      glycosidase by mechanism engineering.
AB  - Glycoside hydrolases are particularly abundant in all areas of metabolism as they
      are involved in the degradation of natural polysaccharides and glycoconjugates.
      These enzymes are classified into 133 families (CAZy server, http://www.cazy.org)
      in which members of each family have a similar structure and catalytic mechanism.
      In order to understand better the structure/function relationships of these
      enzymes and their evolution and to develop new robust evolved glycosidases, we
      undertook to convert a Family 1 thermostable beta-glycosidase into an exo-beta-N
      acetylglucosaminidase. This latter activity is totally absent in Family 1, while
      natural beta-hexosaminidases belong to CAZy Families 3, 20 and 84. Using
      molecular modeling, we first showed that the docking of N-acetyl-d-glucosamine in
      the subsite -1 of the beta-glycosidase from Thermus thermophilus (TtbetaGly)
      suggested several steric conflicts with active site amino-acids (N163, E338)
      induced by the N-acetyl group. Both N163A and N163D-E338G mutations induced
      significant N-acetylglucosaminidase activity in TtbetaGly. The double mutant
      N163D-E338G was also active on the bicyclic oxazoline substrate, suggesting that
      this mutated enzyme uses a catalytic mechanism involving a substrate-assisted
      catalysis with a noncovalent oxazoline intermediate, similar to the N
      acetylglucosaminidases from Families 20 and 84. Furthermore, a very efficient
      trans-N-acetylglucosaminidase activity was observed when the double mutant was
      incubated in the presence of NAG-oxazoline as a donor and N-methyl-O-benzyl-N
      (beta-d-glucopyranosyl)-hydroxylamine as an acceptor. More generally, this work
      demonstrates that it is possible to exchange the specificities and catalytic
      mechanisms with minimal changes between phylogenetically distant protein
      structures. 

PMID- 25378482
TI  - Epithelial-stromal interaction via Notch signaling is essential for the full
      maturation of gut-associated lymphoid tissues.
AB  - Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell
      differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located
      beneath the follicle-associated epithelium (FAE) abundantly express the Notch
      ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding
      a transcription factor implicated in Notch signaling-in intestinal epithelial
      cells have defective GALT maturation. This defect can be attributed to the
      expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE.
      These data demonstrate that epithelial Notch signaling maintained by stromal
      cells contributes to the full maturation of GALT by restricting secretory cell
      differentiation in FAE. 

PMID- 25378483
TI  - Foxd3 suppresses NFAT-mediated differentiation to maintain self-renewal of
      embryonic stem cells.
AB  - Pluripotency-associated transcription factor Foxd3 is required for maintaining
      pluripotent cells. However, molecular mechanisms underlying its function are
      largely unknown. Here, we report that Foxd3 suppresses differentiation induced by
      calcineurin-NFAT signaling to maintain the ESC identity. Mechanistically, Foxd3
      interacts with NFAT proteins and recruits co-repressor Tle4, a member of the Tle
      repressor family highly expressed in undifferentiated ESCs, to suppress NFATc3's
      transcriptional activities. Furthermore, global transcriptome analysis shows that
      Foxd3 and NFATc3 co-regulate a set of differentiation-associated genes in ESCs.
      Collectively, our study establishes a molecular and functional link between a
      pluripotency-associated factor and an important ESC differentiation-inducing
      pathway. 

PMID- 25378485
TI  - Replication of boid inclusion body disease-associated arenaviruses is temperature
      sensitive in both boid and mammalian cells.
AB  - Boid inclusion body disease (BIDB) is a fatal disease of boid snakes, the
      etiology of which has only recently been revealed following the identification of
      several novel arenaviruses in diseased snakes. BIBD-associated arenaviruses
      (BIBDAV) are genetically divergent from the classical Old and New World
      arenaviruses and also differ substantially from each other. Even though there is
      convincing evidence that BIBDAV are indeed the etiological agent of BIBD, the
      BIBDAV reservoir hosts--if any exist besides boid snakes themselves--are not yet
      known. In this report, we use University of Helsinki virus (UHV; a virus that we
      isolated from a Boa constrictor with BIBD) to show that BIBDAV can also replicate
      effectively in mammalian cells, including human cells, provided they are cultured
      at 30 degrees C. The infection induces the formation of cytoplasmic inclusion
      bodies (IB), comprised mainly of viral nucleoprotein (NP), similar to those
      observed in BIBD and in boid cell cultures. Transferring infected cells from 30
      degrees C to 37 degrees C ambient temperature resulted in progressive declines in
      IB formation and in the amounts of viral NP and RNA, suggesting that BIBDAV
      growth is limited at 37 degrees C. These observations indirectly indicate that IB
      formation is linked to viral replication. In addition to mammalian and reptilian
      cells, UHV infected arthropod (tick) cells when grown at 30 degrees C. Even
      though our findings suggest that BIBDAV have a high potential to cross the
      species barrier, their inefficient growth at mammalian body temperatures
      indicates that the reservoir hosts of BIBDAV are likely species with a lower body
      temperature, such as snakes. IMPORTANCE: The newly discovered boid inclusion body
      disease-associated arenaviruses (BIBDAV) of reptiles have drastically altered the
      phylogeny of the family Arenavirus. Prior to their discovery, known arenaviruses
      were considered mainly rodent-borne viruses, with each arenavirus species having
      its own reservoir host. BIBDAV have so far been demonstrated in captive boid
      snakes, but their possible reservoir host(s) have not yet been identified. Here
      we show, using University of Helsinki virus as a model, that these viruses are
      able to infect mammalian (including human) and arthropod cells. Our results
      provide in vitro proof of the considerable ability of arenaviruses to cross
      species barriers. However, our data indicate that BIBDAV growth occurs at 30
      degrees C but is inhibited at 37 degrees C, implying that crossing of the species
      barrier would be hindered by the body temperature of mammalian species.

PMID- 25378484
TI  - MicroRNA miR-21 attenuates human cytomegalovirus replication in neural cells by
      targeting Cdc25a.
AB  - Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth
      defects, primarily manifesting as neurological disorders. HCMV infection alters
      expression of cellular microRNAs (miRs) and induces cell cycle arrest, which in
      turn modifies the cellular environment to favor virus replication. Previous
      observations found that HCMV infection reduces miR-21 expression in neural
      progenitor/stem cells (NPCs). Here, we show that infection of NPCs and U-251MG
      cells represses miR-21 while increasing the levels of Cdc25a, a cell cycle
      regulator and known target of miR-21. These opposing responses to infection
      prompted an investigation of the relationship between miR-21, Cdc25a, and viral
      replication. Overexpression of miR-21 in NPCs and U-251MG cells inhibited viral
      gene expression, genome replication, and production of infectious progeny, while
      shRNA-knockdown of miR-21 in U-251MG cells increased viral gene expression. In
      contrast, overexpression of Cdc25a in U-251MG cells increased viral gene
      expression and production of infectious progeny and overcame the inhibitory
      effects of miR-21 overexpression. Three viral gene products-IE1, pp71, and UL26
      were shown to inhibit miR-21 expression at the transcriptional level. These
      results suggest that Cdc25a promotes HCMV replication and elevation of Cdc25a
      levels after HCMV infection are due in part to HCMV-mediated repression of miR
      21. Thus, miR-21 is an intrinsic antiviral factor that is modulated by HCMV
      infection. This suggests a role for miR-21 downregulation in the
      neuropathogenesis of HCMV infection of the developing CNS. IMPORTANCE: Human
      cytomegalovirus (HCMV) is a ubiquitous pathogen and has very high prevalence
      among population, especially in China, and congenital HCMV infection is a major
      cause for birth defects. Elucidating virus-host interactions that govern HCMV
      replication in neuronal cells is critical to understanding the neuropathogenesis
      of birth defects resulting from congenital infection. In this study, we confirm
      that HCMV infection downregulates miR-21 but upregulates Cdc25a. Further
      determined the negative effects of cellular miRNA miR-21 on HCMV replication in
      neural progenitor/stem cells and U-251MG glioblastoma/astrocytoma cells. More
      importantly, our results provide the first evidence that miR-21 negatively
      regulates HCMV replication by targeting Cdc25a, a vital cell cycle regulator. We
      further found that viral gene products of IE1, pp71, and UL26 play roles in
      inhibiting miR-21 expression, which in turn causes increases in Cdc25a and
      benefits HCMV replication. Thus, miR-21 appears to be an intrinsic antiviral
      factor that represents a potential target for therapeutic intervention.

PMID- 25378486
TI  - Complete genome characterization of recent and ancient Belgian pig group A
      rotaviruses and assessment of their evolutionary relationship with human
      rotaviruses.
AB  - Group A rotaviruses (RVAs) are an important cause of diarrhea in young pigs and
      children. An evolutionary relationship has been suggested to exist between pig
      and human RVAs. This hypothesis was further investigated by phylogenetic analysis
      of the complete genomes of six recent (G2P[27], G3P[6], G4P[7], G5P[7], G9P[13],
      and G9P[23]) and one historic (G1P[7]) Belgian pig RVA strains and of all
      completely characterized pig RVAs from around the globe. In contrast to the large
      diversity of genotypes found for the outer capsid proteins VP4 and VP7, a
      relatively conserved genotype constellation (I5-R1-C1-M1-A8-N1-T7-E1-H1) was
      found for the other 9 genes in most pig RVA strains. VP1, VP2, VP3, NSP2, NSP4,
      and NSP5 genes of porcine RVAs belonged to genotype 1, which is shared with human
      Wa-like RVAs. However, for most of these gene segments, pig strains clustered
      distantly from human Wa-like RVAs, indicating that viruses from both species have
      entered different evolutionary paths. However, VP1, VP2, and NSP3 genes of some
      archival human strains were moderately related to pig strains. Phylogenetic
      analysis of the VP6, NSP1, and NSP3 genes, as well as amino acid analysis of the
      antigenic regions of VP7, further confirmed this evolutionary segregation. The
      present results also indicate that the species barrier is less strict for pig
      P[6] strains but that chances for successful spread of these strains in the human
      population are hampered by the better adaptation of pig RVAs to pig enterocytes.
      However, future surveillance of pig and human RVA strains is warranted.
      IMPORTANCE: Rotaviruses are an important cause of diarrhea in many species,
      including pigs and humans. Our understanding of the evolutionary relationship
      between rotaviruses from both species is limited by the lack of genomic data on
      pig strains. In this study, recent and ancient Belgian pig rotavirus isolates
      were sequenced, and their evolutionary relationship with human Wa-like strains
      was investigated. Our data show that Wa-like human and pig strains have entered
      different evolutionary paths. Our data indicate that pig P[6] strains form the
      most considerable risk for interspecies transmission to humans. However,
      efficient spread of pig strains in the human population is most likely hampered
      by the adaptation of some crucial viral proteins to the cellular machinery of pig
      enterocytes. These data allow a better understanding of the risk for direct
      interspecies transmission events and the emergence of pig rotaviruses or pig
      human reassortants in the human population.

PMID- 25378487
TI  - A conserved regulatory module at the C terminus of the papillomavirus E1 helicase
      domain controls E1 helicase assembly.
AB  - Viruses frequently combine multiple activities into one polypeptide to conserve
      coding capacity. This strategy creates regulatory challenges to ascertain that
      the combined activities are compatible and do not interfere with each other. The
      papillomavirus E1 protein, as many other helicases, has the intrinsic ability to
      form hexamers and double hexamers (DH) that serve as the replicative DNA
      helicase. However, E1 also has the more unusual ability to generate local melting
      by forming a double trimer (DT) complex that can untwist the double-stranded
      origin of DNA replication (ori) DNA in preparation for DH formation. Here we
      describe a switching mechanism that allows the papillomavirus E1 protein to form
      these two different kinds of oligomers and to transition between them. We show
      that a conserved regulatory module attached to the E1 helicase domain blocks
      hexamer and DH formation and promotes DT formation. In the presence of the
      appropriate trigger, the inhibitory effect of the regulatory module is relieved
      and the transition to DH formation can occur. IMPORTANCE: This study provides a
      mechanistic understanding into how a multifunctional viral polypeptide can
      provide different, seemingly incompatible activities. A conserved regulatory
      sequence module attached to the AAA+ helicase domain in the papillomavirus E1
      protein allows the formation of different oligomers with different biochemical
      activities.

PMID- 25378488
TI  - Two classes of broadly neutralizing antibodies within a single lineage directed
      to the high-mannose patch of HIV envelope.
AB  - The high-mannose patch of human immunodeficiency virus (HIV) envelope (Env)
      elicits broadly neutralizing antibodies (bnAbs) during natural infection
      relatively frequently, and consequently, this region has become a major target of
      vaccine design. However, it has also become clear that antibody recognition of
      the region is complex due, at least in part, to variability in neighboring loops
      and glycans critical to the epitopes. bnAbs against this region have some shared
      features and some distinguishing features that are crucial to understand in order
      to design optimal immunogens that can induce different classes of bnAbs against
      this region. Here, we compare two branches of a single antibody lineage, in which
      all members recognize the high-mannose patch. One branch (prototype bnAb PGT128)
      has a 6-amino-acid insertion in CDRH2 that is crucial for broad neutralization.
      Antibodies in this branch appear to favor a glycan site at N332 on gp120, and
      somatic hypermutation is required to accommodate the neighboring V1 loop glycans
      and glycan heterogeneity. The other branch (prototype bnAb PGT130) lacks the
      CDRH2 insertion. Antibodies in this branch are noticeably effective at
      neutralizing viruses with an alternate N334 glycan site but are less able to
      accommodate glycan heterogeneity. We identify a new somatic variant within this
      branch that is predominantly dependent on N334. The crystal structure of PGT130
      offers insight into differences from PGT128. We conclude that different
      immunogens may be required to elicit bnAbs that have the optimal characteristics
      of the two branches of the lineage described. IMPORTANCE: Development of an HIV
      vaccine is of vital importance for prevention of new infections, and it is
      thought that elicitation of HIV bnAbs will be an important component of an
      effective vaccine. Increasingly, bnAbs that bind to the cluster of high-mannose
      glycans on the HIV envelope glycoprotein, gp120, are being highlighted as
      important templates for vaccine design. In particular, bnAbs from IAVI donor 36
      (PGT125 to PGT131) have been shown to be extremely broad and potent. Combination
      of these bnAbs enhanced neutralization breadth considerably, suggesting that an
      optimal immunogen should elicit several antibodies from this family. Here we
      study the evolution of this antibody family to inform immunogen design. We
      identify two classes of bnAbs that differ in their recognition of the high
      mannose patch and show that different immunogens may be required to elicit these
      different classes.

PMID- 25378490
TI  - Rotavirus entry: a deep journey into the cell with several exits.
AB  - Rotaviruses are the leading etiological agents of acute gastroenteritis in
      infants and young children worldwide. These nonenveloped viruses enter cells
      using different types of endocytosis and, depending on the virus strain, travel
      to different endosomal compartments before exiting to the cytosolic space. In
      this Gem, we review the viral and cellular factors involved in the different
      stages of a productive virus cell entry and share with the readers the journey
      that we have taken into the cell to learn about virus entry. 

PMID- 25378489
TI  - Cognate CD4 T-cell licensing of dendritic cells heralds anti-cytomegalovirus CD8
      T-cell immunity after human allogeneic umbilical cord blood transplantation.
AB  - Reactivation of human cytomegalovirus (CMV) is hazardous to patients undergoing
      allogeneic cord blood transplantation (CBT), lowering survival rates by
      approximately 25%. While antiviral treatment ameliorates viremia, complete viral
      control requires CD8+ T-cell-driven immunity. Mouse studies suggest that cognate
      antigen-specific CD4+ T-cell licensing of dendritic cells (DCs) is required to
      generate effective CD8+ T-cell responses. For humans, this was not fully
      understood. We here show that CD4+ T cells are essential for licensing of human
      DCs to generate effector and memory CD8+ T-cell immunity against CMV in CBT
      patients. First, we show in CBT recipients that clonal expansion of CMV-pp65
      specific CD4+ T cells precedes the rise in CMV-pp65-specific CD8+ T cells.
      Second, the elicitation of CMV-pp65-specific CD8+ T cells from rare naive
      precursors in cord blood requires DC licensing by cognate CMV-pp65-specific CD4+
      T cells. Finally, also CD8+ T-cell memory responses require CD4+ T-cell-mediated
      licensing of DCs in our system, by secretion of gamma interferon (IFN-gamma) by
      pp65-specific CD4+ T cells. Together, these data show that human DCs require
      licensing by cognate antigen-specific CD4+ T cells to elicit effective CD8+ T
      cell-mediated immunity and fight off viral reactivation in CBT patients.
      IMPORTANCE: Survival rates after stem cell transplantation are lowered by 25%
      when patients undergo reactivation of cytomegalovirus (CMV) that they harbor.
      Immune protection against CMV is mostly executed by white blood cells called
      killer T cells. We here show that for generation of optimally protective killer T
      cell responses that respond to CMV, the early elicitation of help from a second
      branch of CMV-directed T cells, called helper T cells, is required.

PMID- 25378491
TI  - Chronic administration of Delta9-tetrahydrocannabinol induces intestinal anti
      inflammatory microRNA expression during acute simian immunodeficiency virus
      infection of rhesus macaques.
AB  - Recreational and medical use of cannabis among human immunodeficiency virus (HIV)
      infected individuals has increased in recent years. In simian immunodeficiency
      virus (SIV)-infected macaques, chronic administration of Delta9
      tetrahydrocannabinol (Delta9-THC) inhibited viral replication and intestinal
      inflammation and slowed disease progression. Persistent gastrointestinal
      disease/inflammation has been proposed to facilitate microbial translocation and
      systemic immune activation and promote disease progression. Cannabinoids
      including Delta9-THC attenuated intestinal inflammation in mouse colitis models
      and SIV-infected rhesus macaques. To determine if the anti-inflammatory effects
      of Delta9-THC involved differential microRNA (miRNA) modulation, we profiled
      miRNA expression at 14, 30, and 60 days postinfection (days p.i.) in the
      intestine of uninfected macaques receiving Delta9-THC (n=3) and SIV-infected
      macaques administered either vehicle (VEH/SIV; n=4) or THC (THC/SIV; n=4).
      Chronic Delta9-THC administration to uninfected macaques significantly and
      positively modulated intestinal miRNA expression by increasing the total number
      of differentially expressed miRNAs from 14 to 60 days p.i. At 60 days p.i., ~28%
      of miRNAs showed decreased expression in the VEH/SIV group compared to none
      showing decrease in the THC/SIV group. Furthermore, compared to the VEH/SIV
      group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b,
      miR-145, miR-149, and miR-187, previously been shown to target proinflammatory
      molecules. NOX4, a potent reactive oxygen species generator, was confirmed as a
      direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was
      detected in VEH/SIV macaques compared to the THC/SIV group. We speculate that miR
      99b-mediated NOX4 downregulation may protect the intestinal epithelium from
      oxidative stress-induced damage. These results support a role for differential
      miRNA induction in THC-mediated suppression of intestinal inflammation. Whether
      similar miRNA modulation occurs in other tissues requires further investigation.
      IMPORTANCE: Gastrointestinal (GI) tract disease/inflammation is a hallmark of
      HIV/SIV infection. Previously, we showed that chronic treatment of SIV-infected
      macaques with Delta9-tetrahydrocannabinol (Delta9-THC) increased survival and
      decreased viral replication and infection-induced gastrointestinal inflammation.
      Here, we show that chronic THC administration to SIV-infected macaques induced an
      anti-inflammatory microRNA expression profile in the intestine at 60 days p.i.
      These included several miRNAs bioinformatically predicted to directly target
      CXCL12, a chemokine known to regulate lymphocyte and macrophage trafficking into
      the intestine. Specifically, miR-99b was significantly upregulated in THC-treated
      SIV-infected macaques and confirmed to directly target NADPH oxidase 4 (NOX4), a
      reactive oxygen species generator known to damage intestinal epithelial cells.
      Elevated miR-99b expression was associated with a significantly decreased number
      of NOX4+ epithelial cells in the intestines of THC-treated SIV-infected macaques.
      Overall, our results show that selective upregulation of anti-inflammatory miRNA
      expression contributes to THC-mediated suppression of gastrointestinal
      inflammation and maintenance of intestinal homeostasis.

PMID- 25378492
TI  - Expression of the epidermodysplasia verruciformis-associated genes EVER1 and
      EVER2 is activated by exogenous DNA and inhibited by LMP1 oncoprotein from
      Epstein-Barr virus.
AB  - EVER1 and EVER2 are mutated in epidermodysplasia verruciformis patients, who are
      susceptible to human betapapillomavirus (HPV) infection. It is unknown whether
      their products control the infection of other viruses. Here, we show that the
      expression of both genes in B cells is activated immediately after Epstein-Barr
      virus (EBV) infection, whereas at later stages, it is strongly repressed via
      activation of the NF-kappaB signaling pathway by latent membrane protein 1
      (LMP1). Ectopic expression of EVER1 impairs the ability of EBV to infect B cells.

PMID- 25378493
TI  - Prevention of measles virus infection by intranasal delivery of fusion inhibitor
      peptides.
AB  - Measles virus (MV) infection is undergoing resurgence and remains one of the
      leading causes of death among young children worldwide despite the availability
      of an effective measles vaccine. MV infects its target cells by coordinated
      action of the MV H and the fusion (F) envelope glycoprotein; upon receptor
      engagement by H, the prefusion F undergoes a structural transition, extending and
      inserting into the target cell membrane and then refolding into a postfusion
      structure that fuses the viral and cell membranes. By interfering with this
      structural transition of F, peptides derived from the heptad-repeat (HR) regions
      of F can potently inhibit MV infection at the entry stage. We show here that
      specific features of H's interaction with its receptors modulate the
      susceptibility of MV F to peptide fusion inhibitors. A higher concentration of
      inhibitory peptides is required to inhibit F-mediated fusion when H is engaged to
      its nectin-4 receptor than when H is engaged to its CD150 receptor. Peptide
      inhibition of F may be subverted by continued engagement of receptor by H, a
      finding that highlights the ongoing role of H-receptor interaction after F has
      been activated and that helps guide the design of more potent inhibitory
      peptides. Intranasal administration of these peptides results in peptide
      accumulation in the airway epithelium with minimal systemic levels of peptide and
      efficiently prevents MV infection in vivo in animal models. The results suggest
      an antiviral strategy for prophylaxis in vulnerable and/or immunocompromised
      hosts. IMPORTANCE: Measles virus (MV) infection causes an acute illness that may
      be associated with infection of the central nervous system (CNS) and severe
      neurological disease. No specific treatment is available. We have shown that
      parenterally delivered fusion-inhibitory peptides protect mice from lethal CNS MV
      disease. Here we show, using established small-animal models of MV infection,
      that fusion-inhibitory peptides delivered intranasally provide effective
      prophylaxis against MV infection. Since the fusion inhibitors are stable at room
      temperature, this intranasal strategy is feasible even outside health care
      settings, could be used to protect individuals and communities in case of MV
      outbreaks, and could complement global efforts to control measles.

PMID- 25378494
TI  - The influenza virus neuraminidase protein transmembrane and head domains have
      coevolved.
AB  - Transmembrane domains (TMDs) from single-spanning membrane proteins are commonly
      viewed as membrane anchors for functional domains. Influenza virus neuraminidase
      (NA) exemplifies this concept, as it retains enzymatic function upon proteolytic
      release from the membrane. However, the subtype 1 NA TMDs have become
      increasingly more polar in human strains since 1918, which suggests that
      selection pressure exists on this domain. Here, we investigated the N1 TMD-head
      domain relationship by exchanging a prototypical "old" TMD (1933) with a "recent"
      (2009), more polar TMD and an engineered hydrophobic TMD. Each exchange altered
      the TMD association, decreased the NA folding efficiency, and significantly
      reduced viral budding and replication at 37 degrees C compared to at 33 degrees
      C, at which NA folds more efficiently. Passaging the chimera viruses at 37
      degrees C restored the NA folding efficiency, viral budding, and infectivity by
      selecting for NA TMD mutations that correspond with their polar or hydrophobic
      assembly properties. These results demonstrate that single-spanning membrane
      protein TMDs can influence distal domain folding, as well as membrane-related
      processes, and suggest the NA TMD in H1N1 viruses has become more polar to
      maintain compatibility with the evolving enzymatic head domain. IMPORTANCE: The
      neuraminidase (NA) protein from influenza A viruses (IAVs) functions to promote
      viral release and is one of the major surface antigens. The receptor-destroying
      activity in NA resides in the distal head domain that is linked to the viral
      membrane by an N-terminal hydrophobic transmembrane domain (TMD). Over the last
      century, the subtype 1 NA TMDs (N1) in human H1N1 viruses have become
      increasingly more polar, and the head domains have changed to alter their
      antigenicity. Here, we provide the first evidence that an "old" N1 head domain
      from 1933 is incompatible with a "recent" (2009), more polar N1 TMD sequence and
      that, during viral replication, the head domain drives the selection of TMD
      mutations. These mutations modify the intrinsic TMD assembly to restore the head
      domain folding compatibility and the resultant budding deficiency. This likely
      explains why the N1 TMDs have become more polar and suggests the N1 TMD and head
      domain have coevolved.

PMID- 25378495
TI  - Evidence of lymphocytic choriomeningitis virus (LCMV) in domestic mice in Gabon:
      risk of emergence of LCMV encephalitis in Central Africa.
AB  - Lymphocytic choriomeningitis virus (LCMV) can cause acute fatal disease on all
      continents but was never detected in Africa. We report the first detection of
      LCMV RNA in a common European house mouse (Mus musculus domesticus) in Africa.
      Phylogenetic analyses show a close relationship with North American strains.
      These findings suggest that there is a risk of the appearance of LCMV acute
      encephalitis cases. This is a perfect example of virus dissemination by its
      natural host that may have dramatic public health consequences. 

PMID- 25378496
TI  - White spot syndrome virus protein kinase 1 defeats the host cell's iron
      withholding defense mechanism by interacting with host ferritin.
AB  - Iron is an essential nutrient for nearly all living organisms, including both
      hosts and invaders. Proteins such as ferritin regulate the iron levels in a cell,
      and in the event of a pathogenic invasion, the host can use an iron-withholding
      mechanism to restrict the availability of this essential nutrient to the invading
      pathogens. However, pathogens use various strategies to overcome this host
      defense. In this study, we demonstrated that white spot syndrome virus (WSSV)
      protein kinase 1 (PK1) interacted with shrimp ferritin in the yeast two-hybrid
      system. A pulldown assay and 27-MHz quartz crystal microbalance (QCM) analysis
      confirmed the interaction between PK1 and both ferritin and apoferritin. PK1 did
      not promote the release of iron ions from ferritin, but it prevented apoferritin
      from binding ferrous ions. When PK1 was overexpressed in Sf9 cells, the cellular
      labile iron pool (LIP) levels were elevated significantly. Immunoprecipitation
      and atomic absorption spectrophotometry (AAS) further showed that the number of
      iron ions bound by ferritin decreased significantly at 24 h post-WSSV infection.
      Taken together, these results suggest that PK1 prevents apoferritin from iron
      loading, and thus stabilizes the cellular LIP levels, and that WSSV uses this
      novel mechanism to counteract the host cell's iron-withholding defense mechanism.
      IMPORTANCE: We show here that white spot syndrome virus (WSSV) ensures the
      availability of iron by using a previously unreported mechanism to defeat the
      host cell's iron-withholding defense mechanism. This defense is often implemented
      by ferritin, which can bind up to 4,500 iron atoms and acts to sequester free
      iron within the cell. WSSV's novel counterstrategy is mediated by a direct
      protein-protein interaction between viral protein kinase 1 (PK1) and host
      ferritin. PK1 interacts with both ferritin and apoferritin, suppresses
      apoferritin's ability to sequester free iron ions, and maintains the
      intracellular labile iron pool (LIP), and thus the availability of free iron is
      increased within cells.

PMID- 25378497
TI  - Mutations in HIV-1 envelope that enhance entry with the macaque CD4 receptor
      alter antibody recognition by disrupting quaternary interactions within the
      trimer.
AB  - Chimeric simian immunodeficiency virus (SIV)/human immunodeficiency virus (HIV)
      (SHIV) infection of macaques is commonly used to model HIV type 1 (HIV-1)
      transmission and pathogenesis in humans. Despite the fact that SHIVs encode SIV
      antagonists of the known macaque host restriction factors, these viruses require
      additional adaptation for replication in macaques to establish a persistent
      infection. Additional adaptation may be required in part because macaque CD4
      (mCD4) is a suboptimal receptor for most HIV-1 envelope glycoprotein (Env)
      variants. This requirement raises the possibility that adaptation of HIV-1 Env to
      the macaque host leads to selection of variants that lack important biological
      and antigenic properties of the viruses responsible for the HIV-1 pandemic in
      humans. Here, we investigated whether this adaptation process leads to changes in
      the antigenicity and structure of HIV-1 Env. For this purpose, we examined how
      two independent mutations that enhance mCD4-mediated entry, A204E and G312V,
      impact antibody recognition in the context of seven different parental HIV-1 Env
      proteins from diverse subtypes. We also examined HIV-1 Env variants from three
      SHIVs that had been adapted for increased replication in macaques. Our results
      indicate that these different macaque-adapted variants had features in common,
      including resistance to antibodies directed to quaternary epitopes and
      sensitivity to antibodies directed to epitopes in the variable domains (V2 and
      V3) that are buried in the parental, unadapted Env proteins. Collectively, these
      findings suggest that adaptation to mCD4 results in conformational changes that
      expose epitopes in the variable domains and disrupt quaternary epitopes in the
      native Env trimer. IMPORTANCE: These findings indicate the antigenic consequences
      of adapting HIV-1 Env to mCD4. They also suggest that to best mimic HIV-1
      infection in humans when using the SHIV/macaque model, HIV-1 Env proteins should
      be identified that use mCD4 as a functional receptor and preserve quaternary
      epitopes characteristic of HIV-1 Env.

PMID- 25378498
TI  - Activation of the chicken type I interferon response by infectious bronchitis
      coronavirus.
AB  - Coronaviruses from both the Alphacoronavirus and Betacoronavirus genera interfere
      with the type I interferon (IFN) response in various ways, ensuring the limited
      activation of the IFN response in most cell types. Of the gammacoronaviruses that
      mainly infect birds, little is known about the activation of the host immune
      response. We show that the prototypical Gammacoronavirus, infectious bronchitis
      virus (IBV), induces a delayed activation of the IFN response in primary renal
      cells, tracheal epithelial cells, and a chicken cell line. In fact, Ifnbeta
      expression is delayed with respect to the peak of viral replication and the
      accompanying accumulation of double-stranded RNA (dsRNA). In addition, we
      demonstrate that MDA5 is the primary sensor for Gammacoronavirus infections in
      chicken cells. Furthermore, we provide evidence that accessory proteins 3a and 3b
      of IBV modulate the response at the transcriptional and translational levels.
      Finally, we show that, despite the lack of activation of the IFN response during
      the early phase of IBV infection, the signaling of nonself dsRNA through both
      MDA5 and TLR3 remains intact in IBV-infected cells. Taken together, this study
      provides the first comprehensive analysis of host-virus interactions of a
      Gammacoronavirus with avian innate immune responses. IMPORTANCE: Our results
      demonstrate that IBV has evolved multiple strategies to avoid the activation of
      the type I interferon response. Taken together, the present study closes a gap in
      the understanding of host-IBV interaction and paves the way for further
      characterization of the mechanisms underlying immune evasion strategies as well
      as the pathogenesis of gammacoronaviruses.

PMID- 25378499
TI  - Class switch recombination and somatic hypermutation of virus-neutralizing
      antibodies are not essential for control of friend retrovirus infection.
AB  - Toll-like receptor 7 and Myd88 are required for antiretroviral antibody and
      germinal center responses, but whether somatic hypermutation and class-switch
      recombination are required for antiretroviral immunity has not been examined.
      Mice deficient in activation-induced cytidine deaminase (AID) resisted Friend
      virus infection, produced virus-neutralizing antibodies, and controlled viremia.
      Passive transfer demonstrated that immune IgM from AID-deficient mice contributes
      to Friend virus control in the presence of virus-specific CD4+ T cells.

PMID- 25378502
TI  - Risk-factor analysis of adjacent-segment pathology requiring surgery following
      anterior, posterior, fusion, and nonfusion cervical spine operations:
      survivorship analysis of 1358 patients.
AB  - BACKGROUND: Adjacent-segment pathology is an important issue involving the
      cervical spine, but there have been few comprehensive studies of this problem.
      The purpose of the current study was to determine the risk factors for adjacent
      segment pathology and to compare the survivorship of adjacent segments in
      patients who underwent cervical spine operations including arthrodesis and motion
      sparing procedures. METHODS: This was a retrospective analysis of a consecutive
      series of 1358 patients with radiculopathy, myelopathy, or myeloradiculopathy who
      underwent cervical spine surgery performed by a single surgeon. We calculated the
      annual incidence of adjacent-segment pathology requiring surgery and, with use of
      Kaplan-Meier analysis, determined survivorship. Cox regression analysis was used
      to identify risk factors. RESULTS: The index surgical procedures included
      cervical arthrodesis (1095 patients; 1038 anterior, twenty-nine posterior, and
      twenty-eight combined anterior and posterior), posterior decompression (214
      patients; 145 laminoplasty and sixty-nine foraminotomy), arthroplasty (thirty-two
      patients), and a combination of arthroplasty and anterior arthrodesis (seventeen
      patients). Secondary surgery on adjacent segments occurred at a relatively
      constant rate of 2.3% per year (95% confidence interval, 1.9 to 2.9). Kaplan
      Meier analysis predicted that 21.9% of patients would need secondary surgery on
      adjacent segments by ten years postoperatively. Factors increasing the risk were
      smoking, female sex, and type of procedure. The posterior arthrodesis group
      (posterior-only or combined anterior and posterior arthrodesis) had a 7.5-times
      greater risk of adjacent-segment pathology requiring reoperation than posterior
      decompression, and a 3.0-times greater risk than the anterior arthrodesis group.
      However, when we compared the anterior cervical arthrodesis group, the
      arthroplasty group (arthroplasty or hybrid arthroplasty), and the posterior
      decompression group to each other, there were no significant differences. Age,
      neurological diagnosis, diabetes, and number of surgically treated segments were
      not significant risk factors. CONCLUSIONS: Patients treated with posterior or
      combined anterior and posterior arthrodesis were far more likely to develop
      clinical adjacent-segment pathology requiring surgery than those treated with
      posterior decompression or anterior arthrodesis. Smokers and women had a higher
      chance of clinical adjacent-segment pathology after cervical spine surgery.

PMID- 25378501
TI  - Short conserved sequences of HIV-1 are highly immunogenic and shift
      immunodominance.
AB  - Cellular immunity is pivotal in HIV-1 pathogenesis but is hampered by viral
      sequence diversity. An approach to minimize this diversity is to focus immunity
      on conserved proteome sequences; therefore, we selected four relatively conserved
      regions (Gag amino acids 148 to 214 and 250 to 335, Env amino acids 521 to 606,
      and Nef amino acids 106 to 148), each created in three mosaics, to provide better
      coverage of M-group HIV-1 sequences. A conserved-region vaccine (CRV) delivering
      genes for these four regions as equal mixtures of three mosaics each (each region
      at a separate injection site) was compared to a whole-protein vaccine (WPV)
      delivering equimolar amounts of genes for whole Gag, Env, and Nef as clade B
      consensus sequences (separate injection sites). Three rhesus macaques were
      vaccinated via three DNA primes and a recombinant adenovirus type 5 boost (weeks
      0, 4, 8, and 24, respectively). Although CRV inserts were about one-fifth that of
      WPV, the CRV generated comparable-magnitude blood CD4+ and CD8+ T lymphocyte
      responses against Gag, Env, and Nef. WPV responses preferentially targeted
      proteome areas outside the selected conserved regions in direct proportion to
      sequence lengths, indicating similar immunogenicities for the conserved regions
      and the outside regions. The CRV yielded a conserved-region targeting density
      that was approximately 5-fold higher than that of the WPV. A similar pattern was
      seen for bronchoalveolar lymphocytes, but with quadruple the magnitudes seen in
      blood. Overall, these findings demonstrate that the selected conserved regions
      are highly immunogenic and that anatomically isolated vaccinations with these
      regions focus immunodominance compared to the case for full-length protein
      vaccination. IMPORTANCE: HIV-1 sequence diversity is a major barrier limiting the
      capability of cellular immunity to contain infection and the ability of vaccines
      to match circulating viral sequences. To date, vaccines tested in humans have
      delivered whole proteins or genes for whole proteins, and it is unclear whether
      including only conserved sequences would yield sufficient cellular
      immunogenicity. We tested a vaccine delivering genes for four small conserved HIV
      1 regions compared to a control vaccine with genes for whole Gag, Env, and Nef.
      Although the conserved regions ranged from 43 to 86 amino acids and comprised
      less than one-fifth of the whole Gag/Env/Nef sequence, the vaccines elicited
      equivalent total magnitudes of both CD4+ and CD8+ T lymphocyte responses. These
      data demonstrate the immunogenicity of these small conserved regions and the
      potential for a vaccine to steer immunodominance toward conserved epitopes.

PMID- 25378500
TI  - Three-dimensional structure of a protozoal double-stranded RNA virus that infects
      the enteric pathogen Giardia lamblia.
AB  - Giardia lamblia virus (GLV) is a small, nonenveloped, nonsegmented double
      stranded RNA (dsRNA) virus infecting Giardia lamblia, the most common protozoan
      pathogen of the human intestine and a major agent of waterborne diarrheal disease
      worldwide. GLV (genus Giardiavirus) is a member of family Totiviridae, along with
      several other groups of protozoal or fungal viruses, including Leishmania RNA
      viruses and Trichomonas vaginalis viruses. Interestingly, GLV is more closely
      related than other Totiviridae members to a group of recently discovered metazoan
      viruses that includes penaeid shrimp infectious myonecrosis virus (IMNV).
      Moreover, GLV is the only known protozoal dsRNA virus that can transmit
      efficiently by extracellular means, also like IMNV. In this study, we used
      transmission electron cryomicroscopy and icosahedral image reconstruction to
      examine the GLV virion at an estimated resolution of 6.0 A. Its outermost
      diameter is 485 A, making it the largest totivirus capsid analyzed to date.
      Structural comparisons of GLV and other totiviruses highlighted a related "T=2"
      capsid organization and a conserved helix-rich fold in the capsid subunits. In
      agreement with its unique capacity as a protozoal dsRNA virus to survive and
      transmit through extracellular environments, GLV was found to be more
      thermoresistant than Trichomonas vaginalis virus 1, but no specific protein
      machinery to mediate cell entry, such as the fiber complexes in IMNV, could be
      localized. These and other structural and biochemical findings provide a basis
      for future work to dissect the cell entry mechanism of GLV into a "primitive"
      (early-branching) eukaryotic host and an important enteric pathogen of humans.
      IMPORTANCE: Numerous pathogenic bacteria, including Corynebacterium diphtheriae,
      Salmonella enterica, and Vibrio cholerae, are infected with lysogenic
      bacteriophages that contribute significantly to bacterial virulence. In line with
      this phenomenon, several pathogenic protozoa, including Giardia lamblia,
      Leishmania species, and Trichomonas vaginalis are persistently infected with
      dsRNA viruses, and growing evidence indicates that at least some of these
      protozoal viruses can likewise enhance the pathogenicity of their hosts.
      Understanding of these protozoal viruses, however, lags far behind that of many
      bacteriophages. Here, we investigated the dsRNA virus that infects the widespread
      enteric parasite Giardia lamblia. Using electron cryomicroscopy and icosahedral
      image reconstruction, we determined the virion structure of Giardia lamblia
      virus, obtaining new information relating to its assembly, stability, functions
      in cell entry and transcription, and similarities and differences with other
      dsRNA viruses. The results of our study set the stage for further mechanistic
      work on the roles of these viruses in protozoal virulence.

PMID- 25378503
TI  - Outcome of total ankle arthroplasty in patients with rheumatoid arthritis and
      noninflammatory arthritis. A multicenter cohort study comparing clinical outcome
      and safety.
AB  - BACKGROUND: Patients with rheumatoid arthritis often have degeneration of the
      ankle and ipsilateral hindfoot joints. Patients with rheumatoid arthritis
      undergoing total ankle arthroplasty have a higher risk of wound breakdown and
      infection. We compared intermediate-term clinical outcomes after total ankle
      arthroplasty in patients with rheumatoid arthritis and patients with
      noninflammatory arthritis. METHODS: Fifty patients with rheumatoid arthritis were
      compared with fifty patients with noninflammatory arthritis (the control group),
      matched for age within ten years, prosthesis type, and follow-up time. All
      patients underwent total ankle arthroplasty. Revisions and major complications
      were noted. Outcome scores included the Ankle Osteoarthritis Scale (AOS) and
      Short Form-36 (SF-36) Health Survey. RESULTS: The groups were similar with
      respect to body mass index and length of follow-up (mean, 63.8 months for the
      rheumatoid arthritis group and 65.6 months for noninflammatory arthritis group);
      the rheumatoid arthritis group was younger (mean, 58.5 years compared with 61.2
      years). The mean AOS pain scores were significantly different in the rheumatoid
      arthritis and noninflammatory arthritis groups preoperatively (p < 0.01), but
      were similar following total ankle arthroplasty (mean and standard deviation,
      18.5 +/- 17.8 for the rheumatoid arthritis group and 19.7 +/- 16.5 for the
      noninflammatory arthritis group; p = 0.93). Both groups showed significant
      improvement (p < 0.05) with regard to the AOS scores for pain and disability and
      SF-36 physical component summary scores following surgery. Postoperatively, AOS
      disability and SF-36 physical component summary scores were better for patients
      with noninflammatory arthritis. There were seven revisions in the rheumatoid
      arthritis group and five in noninflammatory arthritis group. There was one major
      wound complication in the rheumatoid arthritis cohort and none in the control
      cohort. CONCLUSIONS: Patients with rheumatoid arthritis benefit from total ankle
      arthroplasty and have similar outcomes to patients with noninflammatory
      arthritis. The overall pain and disability were worse for patients with
      rheumatoid arthritis than for those with noninflammatory arthritis
      preoperatively, but this did not negatively influence their final outcomes. When
      properly treated, patients with rheumatoid arthritis achieve good results.

PMID- 25378504
TI  - A novel approach for determining three-dimensional acetabular orientation:
      results from two hundred subjects.
AB  - BACKGROUND: The inherently complex three-dimensional morphology of both the
      pelvis and acetabulum create difficulties in accurately determining acetabular
      orientation. Our objectives were to develop a reliable and accurate methodology
      for determining three-dimensional acetabular orientation and to utilize it to
      describe relevant characteristics of a large population of subjects without
      apparent hip pathology. METHODS: High-resolution computed tomography studies of
      200 patients previously receiving pelvic scans for indications not related to
      orthopaedic conditions were selected from our institution's database. Three
      dimensional models of each osseous pelvis were generated to extract specific
      anatomical data sets. A novel computational method was developed to determine
      standard measures of three-dimensional acetabular orientation within an
      automatically identified anterior pelvic plane reference frame. Automatically
      selected points on the osseous ridge of the acetabulum were used to generate a
      best-fit plane for describing acetabular orientation. RESULTS: Our method showed
      excellent interobserver and intraobserver agreement (an intraclass correlation
      coefficient [ICC] of >0.999) and achieved high levels of accuracy. A significant
      difference between males and females in both anteversion (average, 3.5 degrees ;
      95% confidence interval [CI], 1.9 degrees  to 5.1 degrees  across all angular
      definitions; p < 0.0001) and inclination (1.4 degrees ; 95% CI, 0.6 degrees  to
      2.3 degrees  for anatomic angular definition; p < 0.002) was observed.
      Intrapatient asymmetry in anatomic measures showed bilateral differences in
      anteversion (maximum, 12.1 degrees ) and in inclination (maximum, 10.9 degrees ).
      CONCLUSIONS: Significant differences in acetabular orientation between the sexes
      can be detected only with accurate measurements that account for the entire
      acetabulum. While a wide range of interpatient acetabular orientations was
      observed, the majority of subjects had acetabula that were relatively symmetrical
      in both inclination and anteversion. CLINICAL RELEVANCE: A highly accurate and
      reproducible method for determining the orientation of the acetabulum's aperture
      will benefit both surgeons and patients, by further refining the distinctions
      between normal and abnormal hip characteristics. Enhanced understanding of the
      acetabulum could be useful in the diagnostic, planning, and execution stages for
      surgical procedures of the hip or in advancing the design of new implant systems.

PMID- 25378505
TI  - Anteverting periacetabular osteotomy for symptomatic acetabular retroversion:
      results at ten years.
AB  - BACKGROUND: Acetabular retroversion is associated with pincer-type
      femoroacetabular impingement and can lead to hip osteoarthritis. We report the
      ten-year results of a previously described patient cohort that had corrective
      periacetabular osteotomy for the treatment of symptomatic acetabular
      retroversion. METHODS: Clinical and radiographic parameters were assessed
      preoperatively and at two and ten years postoperatively. A Kaplan-Meier
      survivorship analysis of the twenty-two patients (twenty-nine hips) with a mean
      follow-up (and standard deviation) of 11 +/- 1 years (range, nine to twelve
      years) was performed. In addition, a univariate Cox regression analysis was done
      with conversion to total hip arthroplasty as the primary end point and
      progression of the osteoarthritis, a fair or poor result according to the Merle
      d'Aubigne score, or the need for revision surgery as the secondary end points.
      RESULTS: The mean Merle d'Aubigne score improved significantly from 14 +/- 1.4
      points (range, 12 to 17 points) preoperatively to 16.9 +/- 0.9 points (range, 15
      to 18 points) at ten years (p < 0.001). There were also significant improvements
      with regard to hip flexion (p = 0.003), internal rotation (p = 0.003), and
      adduction (p = 0.002) compared with the preoperative status. No significant
      increase of the mean Tonnis osteoarthritis score was seen at ten years (p =
      0.06). The cumulative ten-year survivorship, with conversion to a total hip
      arthroplasty as the primary end point, was 100%. The cumulative ten-year
      survivorship in achievement of one of the secondary end points was 71% (95%
      confidence interval, 54% to 88%). Predictors for poor outcome were the lack of
      femoral offset creation and overcorrection of the acetabular version resulting in
      excessive anteversion. CONCLUSIONS: Anteverting periacetabular osteotomy for
      acetabular retroversion leads to favorable long-term results with preservation of
      the native hip at a mean of ten years. Overcorrection resulting in excessive
      anteversion of the hip and omitting concomitant offset creation of the femoral
      head-neck junction are associated with an unfavorable outcome.

PMID- 25378506
TI  - Supracondylar humeral fractures with isolated anterior interosseous nerve
      injuries: is urgent treatment necessary?
AB  - BACKGROUND: It is unclear if pediatric patients with a supracondylar humeral
      fracture and isolated anterior interossous nerve injury require urgent treatment.
      METHODS: A retrospective, multicenter study of 4409 patients with operatively
      treated supracondylar humeral fractures was conducted. Exclusion criteria were
      additional nerve injuries other than the anterior interosseous nerve, any sensory
      changes, pulselessness, ipsilateral forearm fractures, open fractures, less than
      two months of follow-up, or pathological fractures. RESULTS: Thirty-five of 4409
      patients met inclusion criteria. The average time to surgery was 14.6 hours
      (range, two to thirty-six hours). No patient developed compartment syndrome.
      There was no significant difference in time to return of anterior interosseous
      nerve function relative to the time to surgical reduction and fixation (p =
      0.668). A complete return of anterior interosseous nerve function occurred in all
      patients with an average time of forty-nine days (range, two to 224 days). Ninety
      percent of patients recovered anterior interosseous nerve function by 149 days.
      CONCLUSIONS: To our knowledge, this is the largest series to date of
      supracondylar humeral fractures with anterior interosseous nerve injuries. There
      is no evidence that a supracondylar humeral fracture with an isolated anterior
      interosseous nerve injury requires urgent treatment. A delay in treatment up to
      twenty-four hours was not associated with an increased time of nerve recovery or
      other complications. This series excluded patients with sensory nerve injuries,
      pulselessness, and ipsilateral forearm fractures, which all may require urgent
      surgery. Barring other clinical indications for urgent treatment of a
      supracondylar humeral fracture, an isolated anterior interosseous nerve injury
      (no sensory changes) may not by itself be an indication for urgent surgery. The
      anterior interosseous nerve injuries in this series showed complete recovery at a
      mean time of forty-nine days.

PMID- 25378507
TI  - Improving residency training in arthroscopic knee surgery with use of a virtual
      reality simulator. A randomized blinded study.
AB  - BACKGROUND: There is a paucity of articles in the surgical literature
      demonstrating transfer validity (transfer of training). The purpose of this study
      was to assess whether skills learned on the ArthroSim virtual-reality
      arthroscopic knee simulator transferred to greater skill levels in the operating
      room. METHODS: Postgraduate year-3 orthopaedic residents were randomized into
      simulator-trained and control groups at seven academic institutions. The
      experimental group trained on the simulator, performing a knee diagnostic
      arthroscopy procedure to a predetermined proficiency level based on the average
      proficiency of five community-based orthopaedic surgeons performing the same
      procedure on the simulator. The residents in the control group continued their
      institution-specific orthopaedic education and training. Both groups then
      performed a diagnostic knee arthroscopy procedure on a live patient. Video
      recordings of the arthroscopic surgery were analyzed by five pairs of expert
      arthroscopic surgeons blinded to the identity of the residents. A proprietary
      global rating scale and a procedural checklist, which included visualization and
      probing scales, were used for rating. RESULTS: Forty-eight (89%) of the fifty
      four postgraduate year-3 residents from seven academic institutions completed the
      study. The simulator-trained group averaged eleven hours of training on the
      simulator to reach proficiency. The simulator-trained group performed
      significantly better when rated according to our procedural checklist (p =
      0.031), including probing skills (p = 0.016) but not visualization skills (p =
      0.34), compared with the control group. The procedural checklist weighted probing
      skills double the weight of visualization skills. The global rating scale failed
      to reach significance (p = 0.061) because of one extreme outlier. The duration of
      the procedure was not significant. This lack of a significant difference seemed
      to be related to the fact that residents in the control group were less thorough,
      which shortened their time to completion of the arthroscopic procedure.
      CONCLUSIONS: We have demonstrated transfer validity (transfer of training) that
      residents trained to proficiency on a high-fidelity realistic virtual-reality
      arthroscopic knee simulator showed a greater skill level in the operating room
      compared with the control group. CLINICAL RELEVANCE: We believe that the results
      of our study will stimulate residency program directors to incorporate surgical
      simulation into the core curriculum of their residency programs.

PMID- 25378508
TI  - Comparison of highly cross-linked and conventional polyethylene in posterior
      cruciate-substituting total knee arthroplasty in the same patients.
AB  - BACKGROUND: We are not aware of any information on in vivo clinical results at a
      minimum of five years after posterior cruciate-substituting total knee
      arthroplasties performed with a highly cross-linked polyethylene insert. The
      purpose of the study was to evaluate whether the clinical and radiographic
      results of posterior cruciate-substituting total knee prostheses, including the
      prevalences of fracture of the polyethylene post, failure of the locking
      mechanism of the tibial polyethylene insert, and osteolysis, would be similar
      between patients treated with conventional polyethylene and those treated with
      highly cross-linked polyethylene. METHODS: Three hundred and eight patients with
      a mean age of 60.3 years (range, twenty-two to sixty-five years) received a
      posterior cruciate-substituting total knee prosthesis with a conventional
      polyethylene tibial insert in one knee and the same prosthesis with a highly
      cross-linked polyethylene tibial insert in the contralateral knee. Twenty
      patients were men and 288 were women. The mean duration of follow-up was 5.9
      years (range, five to 6.8 years). At each follow-up visit, the patients were
      assessed radiographically and clinically with the rating system of the Knee
      Society; the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC); and the University of California, Los Angeles (UCLA) activity score.
      RESULTS: The two groups did not differ significantly (p > 0.05) with regard to
      the mean postoperative Knee Society total knee scores (93.5 compared with 93.7
      points), function scores (82.9 compared with 82.7 points), and pain scores (46.7
      compared with 47.1 points); WOMAC scores (16 compared with 15 points); range of
      motion (129.7 degrees  compared with 130.1 degrees ); or patient satisfaction
      assessed with a visual analog scale (7.6 compared with 7.9 points). The mean UCLA
      activity score was 6.4 points (p > 0.05). There were no significant differences
      between the two groups with regard to radiographic results. No knee in either
      group had a fracture of the tibial polyethylene post or failure of the locking
      mechanism of the tibial polyethylene insert. No knee in either group had
      osteolysis. One knee (0.3%), treated with highly cross-linked polyethylene, was
      revised because of infection. CONCLUSIONS: The data suggest that clinical and
      radiographic findings at five years after posterior cruciate-substituting total
      knee arthroplasty were the same for the patients treated with highly cross-linked
      polyethylene and those treated with conventional polyethylene.

PMID- 25378509
TI  - Thirty-five-year results after Charnley total hip arthroplasty in patients less
      than fifty years old. A concise follow-up of previous reports.
AB  - We report the updated results for a previously described cohort of patients who
      were less than fifty years old at the time of the index Charnley total hip
      arthroplasty with cement. The original cohort consisted of ninety-three
      consecutive hips in sixty-nine patients. The patients were followed for a minimum
      of thirty-five years after surgery or until death. At the latest follow-up
      evaluation, there were forty-one total hip replacements (44%) in thirty-two
      living patients. Thirty-four (37%) of the ninety-three total hip replacements in
      the original cohort had been revised or removed. Twenty acetabular (22%) and
      seven femoral (8%) components had been revised for aseptic loosening. Since the
      twenty-five-year follow-up, the average six-minute-walk distance decreased from
      395 m to 171 m, and this decrease correlated with increasing comorbidity. This
      study demonstrates the durability of cemented total hip replacements in a young
      patient population. Although 63% (fifty-nine) of the ninety-three original hip
      replacements were functioning at the latest follow-up or at the time of death, a
      significant decrease in activity level was seen over time (p < 0.001). Of the
      forty-one original implants in the patients who were alive at the time of the
      thirty-five-year follow-up, only 46% (nineteen) were retained.

PMID- 25378510
TI  - Distal radial fractures in older men. A missed opportunity?
AB  - BACKGROUND: Fractures of the distal aspect of the radius are common, yet little
      is known about this type of fracture among older men. The purpose of this study
      was to compare fracture characteristics, treatment, and osteoporosis evaluation
      among men and women who had sustained a distal radial fracture. We hypothesized
      that the men would have similar patterns of injury and lower rates of evaluation
      for osteoporosis. METHODS: We retrospectively reviewed the medical records of
      ninety-five men and 344 women over the age of fifty years who were treated for a
      distal radial fracture at a single institution over a five-year period. We
      assessed whether the patients had received a dual x-ray absorptiometry (DXA) scan
      and osteoporosis treatment within six months following the injury. Multivariate
      analysis identified independent predictors of bone mineral density (BMD) testing
      and osteoporosis treatment. RESULTS: Men had less severe fractures than women (a
      Type-C fracture rate of 20% for men compared with 40% for women; p = 0.014).
      While 184 (53%) of the women had a DXA scan after injury, only seventeen (18%) of
      the men were evaluated (p < 0.001). Among the patients who underwent DXA scan,
      nine men (9% of men overall) and sixty-five women (19% of women overall) had a
      diagnosis of osteoporosis (p = 0.01). Male sex was an independent predictor of
      failure to undergo BMD testing as well as receive subsequent treatment with
      calcium and vitamin D or bisphosphonates (p < 0.001). CONCLUSIONS: Significantly
      fewer men received evaluation for osteoporosis following a distal radial
      fracture, with rates of evaluation unacceptably low according to published
      guidelines.

PMID- 25378511
TI  - Are serum lipids involved in primary frozen shoulder? A case-control study.
AB  - BACKGROUND: Hyperlipidemia is a proposed, but unproven, risk factor for primary
      frozen shoulder. The purpose of this study was to evaluate the association
      between serum lipid profiles and primary frozen shoulder. METHODS: This was a
      case-control study. The case group comprised 300 patients diagnosed with frozen
      shoulder from October 2009 to April 2013. Patients with diabetes, thyroid
      disease, or previous shoulder surgery or trauma were excluded. The control group
      comprised 900 age and sex-matched persons with normal shoulder function who
      visited our health promotion center for general check-ups during the same period.
      We calculated the odds ratios and 95% confidence intervals to identify any
      association between serum lipid level and primary frozen shoulder, using
      conditional logistic regression analysis. We evaluated continuous data on the
      serum levels of total cholesterol, calculated low-density lipoprotein, measured
      low-density lipoprotein, high-density lipoprotein, triglyceride, and non-high
      density lipoprotein cholesterol. We also evaluated categorical data on hyper
      cholesterolemia, hyper-low-density lipoproteinemia (calculated and measured),
      hyper-high-density lipoproteinemia, hyper-triglyceridemia, and hyper-non-high
      density lipoprotein cholesterolemia. RESULTS: Univariate analysis of the
      continuous data showed total cholesterol (odds ratio, 1.010 [95% confidence
      interval, 1.006 to 1.013]; p < 0.001), calculated low-density lipoprotein (odds
      ratio, 1.008 [95% confidence interval, 1.004 to 1.012]; p < 0.001), measured low
      density lipoprotein (odds ratio, 1.007 [95% confidence interval, 1.003 to 1.011];
      p = 0.001), high-density lipoprotein (odds ratio, 1.015 [95% confidence interval,
      1.006 to 1.024]; p = 0.001), and non-high-density lipoprotein cholesterol (odds
      ratio, 1.007 [95% confidence interval, 1.004 to 1.011]; p < 0.001) to be
      significantly associated with primary frozen shoulder. Univariate analysis of
      categorical values showed hyper-cholesterolemia (odds ratio, 1.789 [95%
      confidence interval, 1.366 to 2.343]; p < 0.001), calculated hyper-low-density
      lipoproteinemia (odds ratio, 1.609 [95% confidence interval, 1.210 to 2.138]; p =
      0.001), measured hyper-low-density lipoproteinemia (odds ratio, 1.643 [95%
      confidence interval, 1.190 to 2.269]; p = 0.003), hyper-high-density
      lipoproteinemia (odds ratio, 1.440 [95% confidence interval, 1.062 to 1.953]; p =
      0.019), and hyper-non-high-density lipoprotein cholesterolemia (odds ratio, 1.645
      [95% confidence interval, 1.259 to 2.151]; p < 0.001) to be significantly
      associated with primary frozen shoulder. CONCLUSIONS: We conclude that
      hypercholesterolemia and inflammatory lipoproteinemias, particularly hyper-low
      density lipoproteinemia and hyper-non-high-density lipoprotein cholesterolemia,
      have a significant association with primary frozen shoulder. Further research is
      needed to evaluate whether a non-optimal serum lipid level is a cause, a related
      co-factor, or a result of primary frozen shoulder.

PMID- 25378512
TI  - Perioperative blood transfusions in orthopaedic surgery.
AB  - Blood transfusion after orthopaedic surgery accounts for 10% of all packed red
      blood-cell transfusions, but use varies substantially across hospitals and
      surgeons. Transfusions can cause systemic complications, including allergic
      reactions, transfusion-related acute lung injury, transfusion-associated
      circulatory overload, graft-versus-host disease, and infections. Tranexamic acid
      is a new cost-effective blood management tool to reduce blood loss and decrease
      the risk of transfusion after total joint arthroplasty. Current clinical evidence
      does not justify transfusions for a hemoglobin level of >8 g/dL in the absence of
      symptoms. Studies have also supported the use of this trigger in patients with a
      history or risk of cardiovascular disease.

PMID- 25378513
TI  - Medicaid payer status is associated with in-hospital morbidity and resource
      utilization following primary total joint arthroplasty.
AB  - BACKGROUND: Previous reports suggest that there are major disparities in outcomes
      following total joint arthroplasty among patients with different payer statuses.
      The explanation for these differences is largely unknown and may result from
      confounding variables. The Affordable Care Act expansion of Medicaid coverage in
      2014 makes the examination of these disparities particularly relevant. METHODS:
      The Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample
      (NIS) database was used to identify patients who had undergone primary hip or
      knee arthroplasty from 2002 through 2011. Complications, costs, and length of
      hospital stay for patients with Medicaid were compared with those for non
      Medicaid patients. Each Medicaid patient was matched to a non-Medicaid patient
      according to age, sex, race, type of total joint arthroplasty, procedure year,
      hospital characteristics, smoking status, and all twenty-nine comorbidities
      defined in the NIS-modified Elixhauser comorbidity measure. RESULTS: It was
      determined that 191,911 patients who underwent total joint arthroplasty had
      Medicaid payer status (2.8% of the entire total joint arthroplasty population),
      and 107,335 (56%) of these Medicaid patients were matched one to one to a non
      Medicaid patient for all variables for the adjusted analysis. After matching,
      Medicaid patients were found to have a higher prevalence of postoperative in
      hospital infection (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3 to
      2.1), wound dehiscence (OR, 2.2; 95% CI, 1.4 to 3.4), and hematoma or seroma (OR,
      1.3; 95% CI, 1.2 to 1.4) but a lower risk of cardiac complications (OR, 0.7; CI,
      0.6 to 0.9). The length of the hospital stay was longer, total cost was higher,
      and discharge to an inpatient facility was more frequent for patients with
      Medicaid status (p < 0.01). CONCLUSIONS: Compared with non-Medicaid patients,
      Medicaid patients have a significantly higher risk for certain postoperative in
      hospital complications and consume more resources following total joint
      arthroplasty even when the two groups have been matched for patient-related
      factors and comorbid conditions commonly associated with low socioeconomic
      status. Additional work is needed to understand the complex interplay between
      socioeconomic status and outcomes, to ensure appropriate resources are allocated
      to maintain access for this patient population, and to develop appropriate risk
      stratification.

PMID- 25378514
TI  - Management of thoracic insufficiency syndrome in patients with Jarcho-Levin
      syndrome using VEPTRs (vertical expandable prosthetic titanium ribs).
AB  - BACKGROUND: Jarcho-Levin syndrome represents a spectrum of clinical and
      radiographic irregularities including abnormal vertebral segmentation or
      formation defects, rib deformities, and short-trunk dwarfism. These abnormalities
      cause reduced thoracic capacity for lung development, resulting in thoracic
      insufficiency syndrome. In the present study, we reviewed outcome measures
      related to scoliotic curve correction, thoracic growth, and respiratory function
      following VEPTR treatment in patients with Jarcho-Levin syndrome. METHODS: Twenty
      nine patients with Jarcho-Levin syndrome, subclassified as spondylocostal
      dysostosis (SCD) or spondylothoracic dysplasia (STD), were treated with VEPTR
      expansion thoracoplasty and followed for at least two years since the initial
      implantation. Spinal and respiratory measures were collected prior to the initial
      VEPTR implantation, immediately after implantation, and at the most recent follow
      up. RESULTS: VEPTR treatment was associated with improved clinical respiratory
      function and with increases in thoracic height (by 50% in the SCD group and 42%
      in the STD group) and thoracic width (by 37% in the SCD group and 28% in the STD
      group). VEPTR treatment resulted in scoliosis curve correction (improvement in
      the Cobb angle of 41% [22 degrees ] in the SCD group and 26% [3.7 degrees ] in
      the STD group) and in improved thoracic symmetry in patients with SCD. Patients
      with SCD displayed increased lumbar lordosis, and both groups of patients
      developed increased thoracic kyphosis approaching normal. CONCLUSIONS: VEPTR
      treatment improved thoracic symmetry, controlled spinal deformity, and was
      associated with improved clinical respiratory function.

PMID- 25378516
TI  - Financial impact of third-party reimbursement changes for CPT Code 29826:
      experience of a large group practice.
AB  - BACKGROUND: On January 1, 2012, the Centers for Medicare & Medicaid Services
      converted Current Procedural Terminology (CPT) code 29826 (arthroscopic
      acromioplasty) from a stand-alone code to an add-on code and reduced the relative
      value units from 19.58 to 5.24. The goal of this study was to quantify the
      financial impact of this change on a large single-specialty orthopaedic surgery
      practice. METHODS: Custom software was used to query the database that harbors
      billing data for a large single-specialty orthopaedic group. Data were
      independently generated based on patient identification data and insurance class,
      and compared between 2011 and 2012. Codes 29826, 29827 (shoulder arthroscopy,
      rotator cuff repair), 29822 (shoulder arthroscopy, debridement, limited), 29823
      (shoulder arthroscopy, debridement, extensive), and 29824 (shoulder arthroscopy,
      distal claviculectomy) were all searched independently for each year and cross
      referenced with each other and all other shoulder codes. Modifier codes for
      surgical assistants were analyzed separately and subsequently combined with
      primary surgeon data for financial analysis. This included assessment of surgeon
      reimbursement per occurrence of code 29826 and surgeon reimbursement by Medicare
      compared with non-Medicare payers. RESULTS: Code 29826 was used 1536 times in
      2011 and 1410 times in 2012 (-2.59% after correcting for all shoulder arthroscopy
      cases per year). Code 29822 was used significantly more in 2012 both alone
      (1.45%, p = 0.001) and in total (2.45%), but the use of 29823 did not change (p =
      0.17). A combination of three of the five selected codes was used significantly
      less in 2012 (p < 0.001), while the use of any combination of four codes was used
      significantly more in 2012 (p < 0.001). Assistant use did not appreciably change
      between years. Average reimbursement for code 29826 by all payers in 2011 was
      $456.84 and $441.64 in 2012. Average payment by Medicare was $268.58 in 2011 and
      $171.02 in 2012 (-36.3%). Medicare paid 54.3% of other payers per case in 2011
      and 33.1% of other payers in 2012. CONCLUSIONS: Reimbursement for code 29826 by
      non-Medicare payers did not decrease dramatically between 2011 and 2012. However,
      Medicare reimbursement fell substantially.

PMID- 25378517
TI  - Teaming: an approach to the growing complexities in health care: AOA critical
      issues.

PMID- 25378518
TI  - Factors impacting musculoskeletal knowledge and clinical confidence in graduating
      medical students.
AB  - BACKGROUND: Despite the prevalence of musculoskeletal disorders, the degree to
      which medical schools are providing students with the knowledge and confidence to
      treat these problems is unclear. This study evaluated the factors that impact
      musculoskeletal knowledge and clinical confidence among fourth-year medical
      students. METHODS: Over a three-year period, 253 fourth-year medical students
      participated in the study at a single institution. Musculoskeletal knowledge was
      evaluated using a National Board of Medical Examiners' musculoskeletal medicine
      subject examination. Factors analyzed included sex, class year, musculoskeletal
      elective experience, duration of musculoskeletal elective, career choice, and
      musculoskeletal curriculum satisfaction. RESULTS: The participation rate was 95%.
      The mean National Board of Medical Examiners' musculoskeletal assessment score
      (and standard deviation) was 70.7 +/- 9.5 points for all fourth-year medical
      students. Taking a musculoskeletal elective significantly increased knowledge (p
      < 0.001) but not clinical confidence. Increased satisfaction with how
      musculoskeletal medicine was taught was associated with increased clinical
      confidence (p < 0.001). No significant differences were seen if students were
      going into musculoskeletal medicine or primary care for either musculoskeletal
      knowledge or clinical confidence. Multivariate analysis of musculoskeletal
      knowledge found that taking a musculoskeletal elective for two weeks led to an
      increase of 6 points (from a possible 100 points) in the National Board of
      Medical Examiners' subject examination scores. CONCLUSIONS: This study reveals
      that participation in a clinical elective is the only factor that led to a
      significant increase in musculoskeletal knowledge in fourth-year medical
      students. A two-week clinical elective can be sufficient time to have an impact
      on musculoskeletal knowledge, but it alone does not increase clinical confidence.
      Further studies are needed to determine how to improve musculoskeletal clinical
      confidence.

PMID- 25378519
TI  - Shame on us! Men need osteoporosis care, too! Commentary on an article by Carl M.
      Harper, MD, et al.: "Distal radial fractures in older men. A missed
      opportunity?".

PMID- 25378520
TI  - What's good for the heart is good for the shoulder? Commentary on an article by
      Chang-Meen Sung, MD, et al.: "Are serum lipids involved in primary frozen
      shoulder? A case-control study".

PMID- 25378521
TI  - Successful delivery of clinical gastroenterology studies in the UK.

PMID- 25378522
TI  - Strategies for the treatment of Hepatitis C in an era of interferon-free
      therapies: what public health outcomes do we value most?
AB  - OBJECTIVE: The expense of new therapies for HCV infection may force health
      systems to prioritise the treatment of certain patient groups over others. Our
      objective was to forecast the population impact of possible prioritisation
      strategies for the resource-rich setting of Scotland. DESIGN: We created a
      dynamic Markov simulation model to reflect the HCV-infected population in
      Scotland. We determined trends in key outcomes (e.g., incident cases of chronic
      infection and severe liver morbidity (SLM)) until the year 2030, according to
      treatment strategies involving prioritising, either: (A) persons with
      moderate/advanced fibrosis or (B) persons who inject drugs (PWID). RESULTS:
      Continuing to treat the same number of patients with the same characteristics
      will give rise to a fall in incident infection (from 600 cases in 2015 to 440 in
      2030) and a fall in SLM (from 195 cases in 2015 to 145 in 2030). Doubling
      treatment-uptake and prioritising PWID will reduce incident infection to
      negligible levels (<50 cases per year) by 2025, while SLM will stabilise (at 70
      75 cases per year) in 2028. Alternatively, doubling the number of patients
      treated, but, instead, prioritising persons with moderate/advanced fibrosis will
      reduce incident infection less favourably (only to 280 cases in 2030), but SLM
      will stabilise by 2023 (i.e., earlier than any competing strategy). CONCLUSIONS:
      Prioritising treatment uptake among PWID will substantially impact incident
      transmission, however, this approach foregoes the optimal impact on SLM.
      Conversely, targeting those with moderate/advanced fibrosis has the greatest
      impact on SLM but is suboptimal in terms of averting incident infection.

PMID- 25378523
TI  - A no biopsy strategy for adult patients with suspected coeliac disease: making
      the world gluten-free.

PMID- 25378525
TI  - Bleach processed smear for Acid fast bacilli staining in Papua New Guinea.
AB  - The conventional method of processing sputum for acid fast bacilli microscopy has
      been a primary tool for laboratory diagnosis of pulmonary tuberculosis in Papua
      New Guinea. In routine preparation, untreated sputum is directly smeared on a
      glass slide without undergoing any stage of processing. Mounting evidence
      suggests that direct smearing is less sensitive and, to a certain degree,
      compromises infection control. A few alternatives for processing sputum have been
      recommended in the literature; however, their consumables are not easily
      accessible and are expensive for wide use in rural laboratories. The bleach
      concentration and processing method appears to be the most preferable choice
      because bleach is inexpensive, readily available, and has bactericidal
      properties. 

PMID- 25378524
TI  - Epigenetic upregulation of metabotropic glutamate receptor 2 in the spinal cord
      attenuates oestrogen-induced visceral hypersensitivity.
AB  - OBJECTIVE: Epigenetic mechanisms are potential targets to relieve somatic pain.
      However, little is known whether epigenetic regulation interferes with visceral
      pain. Previous studies show that oestrogen facilitates visceral pain. This study
      aimed to determine whether histone hyperacetylation in the spinal cord could
      attenuate oestrogen-facilitated visceral pain. DESIGN: The effect of the histone
      deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on the magnitude of
      the visceromotor response (VMR) to colorectal distention was examined in
      ovariectomised rats with/without oestrogen replacement. An additional interaction
      with the metabotropic glutamate receptor 2/3 (mGluR2/3) antagonist LY341495 was
      tested. The levels of acetylated histone and mGluR2 mRNA and protein were
      analysed. The binding of acetylated H3 and oestrogen receptor alpha (ERalpha) to
      the GRM2 promoter was measured by chromatin immunoprecipitation coupled with
      qPCR. RESULTS: In ovariectomised rats, 17beta-estradiol (E2), but not safflower
      oil, increased the magnitude of the VMR to colorectal distention. SAHA attenuated
      the E2-facilitated VMR, but had no effect in safflower oil-treated rats.
      Subsequent spinal administration of LY341495 reversed the antinociceptive effect
      of SAHA in E2 rats. In addition, SAHA increased mGluR2 mRNA and protein in the
      spinal dorsal horn following E2, but not vehicle, treatment. In contrast, neither
      E2 nor SAHA alone altered mGluR2 mRNA. SAHA increased binding of H3K9ac and
      ERalpha to the same regions of the GRM2 promoter in E2-SAHA-treated animals.
      CONCLUSIONS: Histone hyperacetylation in the spinal cord attenuates the
      pronociceptive effects of oestrogen on visceral sensitivity, suggesting that
      epigenetic regulation may be a potential approach to relieve visceral pain.

PMID- 25378526
TI  - Anti-c (Little c) IgM: An Uncommonly Observed but Expected Phenomenon.
AB  - The c-antigen (little c) is part of the Rh blood group system and is found in
      approximately 80% of the United States population. Anti-c antibody develops in
      individuals sensitized through previous exposure and is associated with acute and
      delayed hemolytic transfusion reactions as well as hemolytic disease of the
      newborn (HDN). Most antibodies produced against Rh antigens are of the
      immunoglobulin (Ig) G type. We present a case of anti-c in a 30-year-old white
      woman who was gravida 2 para 1 (G2P1), whose laboratory workup at the time of
      admission for delivery suggests recent exposure and seroconversion in the latter
      part of her pregnancy, with evidence of the expected but rarely demonstrated
      presence of anti-c IgM and IgG. 

PMID- 25378527
TI  - Achieving universal health coverage goals in Thailand: the vital role of
      strategic purchasing.
AB  - Strategic purchasing is one of the key policy instruments to achieve the
      universal health coverage (UHC) goals of improved and equitable access and
      financial risk protection. Given favourable outcomes of Universal Coverage Scheme
      (UCS), this study synthesized strategic purchasing experiences in the National
      Health Security Office (NHSO) responsible for the UCS in contributing to
      achieving UHC goals. The UCS applied the purchaser-provider split concept where
      NHSO, as a purchaser, is in a good position to enforce accountability by public
      and private providers to the UCS beneficiaries, through active purchasing. A
      comprehensive benefit package resulted in high level of financial risk protection
      as reflected by low incidence of catastrophic health spending and impoverished
      households. The NHSO contracted the District Health System (DHS) network, to
      provide outpatient, health promotion and disease prevention services to the whole
      district population, based on an annual age-adjusted capitation payment. In most
      cases, the DHS was the only provider in a district without competitors.
      Geographical monopoly hampered the NHSO to introduce a competitive contractual
      agreement, but a durable, mutually dependent relationship based on trust was
      gradually evolved, while accreditation is an important channel for quality
      improvement. Strategic purchasing services from DHS achieved a pro-poor
      utilization due to geographical proximity, where travel time and costs were
      minimal. Inpatient services paid by Diagnostic Related Group within a global
      budget ceiling, which is estimated based on unit costs, admission rates and
      admission profiles, contained cost effectively. To prevent potential under
      provisions of the services, some high cost interventions were unbundled from
      closed end payment and paid on an agreed fee schedule. Executing monopsonistic
      purchasing power by NHSO brought down price of services given assured quality.
      Cost saving resulted in more patients served within a finite annual budget. 

PMID- 25378528
TI  - NOXious phosphorylation: Smooth muscle reactive oxygen species production is
      facilitated by direct activation of the NADPH oxidase Nox1.

PMID- 25378529
TI  - Targeting the sodium channel NaV1.5 to specific membrane compartments of cardiac
      cells: not a simple task!

PMID- 25378531
TI  - Till truth makes all things plain: human hearts and stem cells.

PMID- 25378530
TI  - Can endothelial progenitor cells treat patients with refractory angina?

PMID- 25378532
TI  - Letter by Makkar et al regarding article, "Cell therapy for heart failure: a
      comprehensive overview of experimental and clinical studies, current challenges,
      and future directions".

PMID- 25378533
TI  - Response to letter regarding article, "Cell therapy for heart failure: a
      comprehensive overview of experimental and clinical studies, current challenges,
      and future directions".

PMID- 25378534
TI  - Investigating the interaction between the neonatal Fc receptor and monoclonal
      antibody variants by hydrogen/deuterium exchange mass spectrometry.
AB  - The recycling of immunoglobulins by the neonatal Fc receptor (FcRn) is of crucial
      importance in the maintenance of antibody levels in plasma and is responsible for
      the long half-lives of endogenous and recombinant monoclonal antibodies. From a
      therapeutic point of view there is great interest in understanding and modulating
      the IgG-FcRn interaction to optimize antibody pharmacokinetics and ultimately
      improve efficacy and safety. Here we studied the interaction between a full
      length human IgG(1) and human FcRn via hydrogen/deuterium exchange mass
      spectrometry and targeted electron transfer dissociation to map sites perturbed
      by binding on both partners of the IgG-FcRn complex. Several regions in the
      antibody Fc region and the FcRn were protected from exchange upon complex
      formation, in good agreement with previous crystallographic studies of FcRn in
      complex with the Fc fragment. Interestingly, we found that several regions in the
      IgG Fab region also showed reduced deuterium uptake. Our findings indicate the
      presence of hitherto unknown FcRn interaction sites in the Fab region or a
      possible conformational link between the IgG Fc and Fab regions upon FcRn
      binding. Further, we investigated the role of IgG glycosylation in the
      conformational response of the IgG-FcRn interaction. Removal of antibody glycans
      increased the flexibility of the FcRn binding site in the Fc region.
      Consequently, FcRn binding did not induce a similar conformational stabilization
      of deglycosylated IgG as observed for the wild-type glycosylated IgG. Our results
      provide new molecular insight into the IgG-FcRn interaction and illustrate the
      capability of hydrogen/deuterium exchange mass spectrometry to advance structural
      proteomics by providing detailed information on the conformation and dynamics of
      large protein complexes in solution.

PMID- 25378536
TI  - Ion Torrent next-generation sequencing for routine identification of clinically
      relevant mutations in colorectal cancer patients.
AB  - AIMS: To evaluate the accuracy, consumable cost and time around testing (TAT) of
      a next-generation sequencing (NGS) assay, the Ion Torrent AmpliSeq Colon and Lung
      Cancer Panel, as an alternative to Sanger sequencing to genotype KRAS, NRAS and
      BRAF in colorectal cancer patients. METHODS: The Ion Torrent panel was first
      verified on cell lines and on control samples and then prospectively applied to
      routine specimens (n=114), with Sanger sequencing as reference. RESULTS: The Ion
      Torrent panel detected mutant alleles at the 5% level on cell lines and correctly
      classified all control tissues. The Ion Torrent assay was successfully carried
      out on most (95.6%) routine diagnostic samples. Of these, 12 (11%) harboured
      mutations in the BRAF gene and 47 (43%) in either of the two RAS genes, in two
      cases with a low abundance of RAS mutant allele which was missed by Sanger
      sequencing. The mean TAT, from sample receipt to reporting, was 10.4 (Sanger) and
      13.0 (Ion Torrent) working days. The consumable cost for genotyping KRAS, NRAS
      and BRAF was ?196 (Sanger) and ?187 (Ion Torrent). CONCLUSIONS: Ion Torrent
      AmpliSeq Colon and Lung Cancer Panel sequencing is as robust as Sanger sequencing
      in routine diagnostics to select patients for anti-epidermal growth factor
      receptor (EGFR) therapy for metastatic colorectal cancer.

PMID- 25378535
TI  - Iron, inflammation, and early death in adults with sickle cell disease.
AB  - RATIONALE: Patients with sickle cell disease (SCD) have markers of chronic
      inflammation, but the mechanism of inflammation and its relevance to patient
      survival are unknown. OBJECTIVE: To assess the relationship between iron,
      inflammation, and early death in SCD. METHODS AND RESULTS: Using peripheral blood
      mononuclear cell transcriptome profile hierarchical clustering, we classified 24
      patients and 10 controls in clusters with significantly different expression of
      genes known to be regulated by iron. Subsequent gene set enrichment analysis
      showed that many genes associated with the high iron cluster were involved in the
      toll-like receptor system (TLR4, TLR7, and TLR8) and inflammasome complex pathway
      (NLRP3, NLRC4, and CASP1). Quantitative PCR confirmed this classification and
      showed that ferritin light chain, TLR4, and interleukin-6 expression were >100
      fold higher in patients than in controls (P<0.001). Further linking intracellular
      iron and inflammation, 14 SCD patients with a ferroportin Q248H variant that
      causes intracellular iron accumulation had significantly higher levels of
      interleukin-6 and C-reactive protein compared with 14 matched SCD patients with
      the wild-type allele (P<0.05). Finally, in a cohort of 412 patients followed for
      a median period of 47 months (interquartile range, 24-82), C-reactive protein was
      strongly and independently associated with early death (hazard ratio, 3.0; 95%
      confidence interval, 1.7-5.2; P<0.001). CONCLUSIONS: Gene expression markers of
      high intracellular iron in patients with SCD are associated with markers of
      inflammation and mortality. The results support a model in which intracellular
      iron promotes inflammatory pathways, such as the TLR system and the inflammasome,
      identifying important new pathways for additional investigation.

PMID- 25378537
TI  - ERG expression in chondrogenic bone and soft tissue tumours.
AB  - AIM: We studied ERG expression in a large series of chondrogenic bone and soft
      tissue tumours to assess the value of ERG as a possible marker of
      chondroid/cartilaginous differentiation. METHODS: Formalin-fixed, paraffin
      embedded whole sections from 111 bone and soft tissue tumours with chondroid
      differentiation or a morphology that may mimic cartilaginous differentiation were
      retrieved. Immunohistochemistry was performed using anti-ERG monoclonal antibody
      directed against the N terminus. Nuclear staining was scored as negative (<5%),
      1+ (5%-25%), 2+ (26%-50%), 3+ (>51%). RESULTS: Nuclear ERG expression was seen in
      all cases of soft tissue chondroma (8), chondromyxoid fibroma (7), chondroblastic
      osteosarcoma (6) and clear cell chondrosarcoma (1). 10/12 conventional
      chondrosarcomas were also positive for ERG. In cases of dedifferentiated
      chondrosarcoma, the well-differentiated component was positive in 7/9 cases,
      while all dedifferentiated foci were negative. In cases of mesenchymal
      chondrosarcoma, the hyaline cartilage component was positive in 2/4 cases,
      whereas the primitive component in all cases was negative. Variable positivity
      was identified in extraskeletal myxoid chondrosarcomas (4/9), chondroblastomas
      (3/8) and mixed tumours/myoepitheliomas (2/11). Only 1/12 chordoma was positive
      for ERG (1+). Interestingly, 15/17 enchondromas were negative for ERG.
      CONCLUSIONS: In this study, we further characterise the expression of ERG in
      mesenchymal tumours and found relatively constant nuclear ERG expression in
      selected chondrogenic tumours including conventional chondrosarcoma,
      chondromyxoid fibroma, chondroblastic osteosarcoma and clear cell chondrosarcoma.
      We also show that ERG may be a helpful ancillary tool in certain select
      diagnostic scenarios and that awareness of ERG expression in tumours with
      cartilaginous differentiation is important.

PMID- 25378538
TI  - Diffuse decidual leucocytoclastic necrosis and NK cell aggregates: two distinct
      features of miscarriage.
AB  - AIMS: Primary histopathology of miscarriage remains undetermined in the majority
      of cases. This study was conducted to determine histological characteristics
      pertinent to miscarriage. METHODS: The study groups were composed of elective
      abortions (n=29) and miscarriages (n=45) comprised of chromosomally normal (n=15)
      and abnormal cases (n=30). Immunohistochemistry was done against CD3, CD8, TIA-1
      and CD56. RESULTS: Two histological features--diffuse decidual leucocytoclastic
      necrosis (DDLN) and decidual natural killer cell aggregates (NKCA)--were
      relatively common in miscarriages. The frequencies of DDLN and NKCA were
      different between the groups (p<0.05 and p<0.05, respectively). DDLN was found in
      13.8% (4/29) of elective abortions, while it was observed in 60.0% (9/15) and
      23.3% (7/30) of chromosomally normal and abnormal miscarriages, respectively.
      DDLN was more frequent in chromosomally normal miscarriages than in elective
      abortions (p=0.004). NKCA was present in 13.8% (4/29) of elective abortions,
      while being found in 33.3% (5/15) and 43.3% (13/30) of chromosomally normal and
      abnormal miscarriages, respectively. NKCA was more frequent in chromosomally
      abnormal miscarriages than in elective abortions (p=0.020). CONCLUSIONS: The
      findings strongly suggest that defective placentation and abnormal maternal
      immune response are associated with miscarriage. DDLN and NKCA seem to have
      diagnostic values in the pathological evaluation of miscarriage.

PMID- 25378539
TI  - Molecular pathology analyses of two fatal human infections of avian influenza
      A(H7N9) virus.
AB  - AIMS: To investigate the histopathological manifestations of two fatal cases of
      H7N9 influenza A virus infection. METHODS: Pulmonary and hepatic specimens from
      two fatal cases of H7N9 influenza virus infection were examined using H&E
      staining. Additionally, in situ hybridisation was performed with probes (ViewRNA)
      targeting H7N9 RNA and IP-10, interleukin (IL)-6 mRNA. The distribution of
      surfactant protein A (SP-A), surfactant protein B (SP-B), CD3, CD4, CD8, CD68 and
      C4d were determined with immunohistochemistry. RESULTS:  Apart from the typical
      diffuse alveolar damage and hyaline membrane observed in severe influenza
      infection, we detected H7N9 RNA and massive intrapulmonary production of IP-10
      and IL-6 mRNA using in situ hybridisation. Hyperplasia of type II pneumocytes was
      observed by H&E staining and immunohistochemistry. Proliferating macrophages and
      clustered neutrophils in the infected lungs were observed, whereas T lymphocytes,
      especially CD4T helper cells, were markedly depleted. No obvious complement
      deposition was found in lung tissues. CONCLUSIONS:  Our findings suggest that
      H7N9 influenza virus induced an immunological response towards overt pulmonary
      inflammation and systemic lymphopenia which led to intense alveolar damage and
      respiratory failure.

PMID- 25378540
TI  - Endotoxin detection in end-stage kidney disease.
AB  - AIMS: Endotoxin detection assays are not validated for use in end-stage kidney
      disease (ESKD). We investigated the accuracy and precision of the kinetic
      turbidimetric Limulus amoebocyte lysate (LAL) assay to detect endotoxin in plasma
      from patients with ESKD. Optimisation of endotoxin recovery from plasma using the
      detergent Tween 80 was also explored. METHODS: Plasma samples from 7 patients
      with ESKD and 7 healthy subjects were spiked with different concentrations of
      endotoxin. Repeated measurements for endotoxin at each level of spike were
      performed to assess the accuracy and precision of spike recovery. Endotoxin
      recovery in plasma samples diluted in Tween 80 and water was compared. RESULTS:
      Mean endotoxin spike recovery was 111.6% and 125.2% in ESKD and healthy subjects,
      respectively. There was no statistical difference in spike recovery between ESKD
      and healthy plasma. Precision of the LAL assay in plasma spiked with low (0.05
      EU/mL) and high (0.5 EU/mL) concentration of endotoxin spikes was 24.1% and 8.9%,
      respectively. The use of Tween 80 as a diluent for plasma significantly improved
      spike recovery in ESKD plasma (100.1% vs 70.4%, p<0.001). CONCLUSIONS: The
      kinetic LAL turbidimetric assay is a valid tool for the detection of blood
      endotoxin in patients with ESKD, although in blood specimens with low-level
      endotoxemia (<=0.05 EU/mL) the assay may be less accurate and precise. Tween 80
      can be used as a diluent to optimise recovery of endotoxin in ESKD plasma.

PMID- 25378541
TI  - Giant cell tumor of bone.

PMID- 25378542
TI  - In reply.

PMID- 25378543
TI  - Thoracentesis outcomes: a 12-year experience.
AB  - BACKGROUND: Despite a lack of evidence in the literature, several assumptions
      exist about the safety of thoracentesis in clinical guidelines and practice
      patterns. We aimed to evaluate specific demographic and clinical factors that
      have been commonly associated with complications such as iatrogenic pneumothorax,
      re-expansion pulmonary oedema (REPE) and bleeding. METHODS: We performed a cohort
      study of inpatients who underwent thoracenteses at Cedars-Sinai Medical Center
      (CSMC) from August 2001 to October 2013. Data were collected prospectively
      including information on volume of fluid removed, procedure side, whether the
      patient was on positive pressure ventilation, number of needle passes and supine
      positioning. Iatrogenic pneumothorax, REPE and bleeding were tracked for 24 h
      after the procedure or until a clinical question was reconciled. Demographic and
      clinical characteristics were obtained through query of electronic medical
      records. RESULTS: CSMC performed 9320 inpatient thoracenteses on 4618 patients
      during the study period. There were 57 (0.61%) iatrogenic pneumothoraces, 10
      (0.01%) incidents of REPE and 17 (0.18%) bleeding episodes. Iatrogenic
      pneumothorax was significantly associated with removal of >1500 mL fluid
      (p<0.0001), unilateral procedures (p=0.001) and more than one needle pass through
      the skin (p=0.001). For every 1 mL of fluid removed there was a 0.18% increased
      risk of REPE (95% CI 0.09% to 0.26%). There were no significant associations
      between bleeding and demographic or clinical variables including International
      Normalised Ratio, partial thromboplastin time and platelet counts. CONCLUSIONS:
      Our series of thoracenteses had a very low complication rate. Current clinical
      guidelines and practice patterns may not reflect evidence-based best practices.

PMID- 25378544
TI  - Non-coding RNAs and respiratory disease.
AB  - Recent scientific developments have radically changed the way we look at the vast
      'non-coding' part of our genome. It is now clear that this genomic 'dark matter'
      is transcribed into myriads of RNA species that act behind the scenes to veto, or
      boost, the production of proteins in our cells. As a consequence, non-coding RNAs
      (ncRNAs) represent an additional layer of regulation for fundamental biological
      processes such as organ development, tissue repair and immunity. It also follows
      that disturbances in ncRNA networks (among which microRNAs and long ncRNAs are
      the best studied) can give rise to a whole range of pathological conditions.
      Increasing preclinical and translational evidence places ncRNAs as key players in
      a wide spectrum of diseases affecting the lung. In this concise review, we will
      provide essential concepts of ncRNA science, with special emphasis on discoveries
      relevant to the pulmonary physician. 

PMID- 25378545
TI  - Diabetes mellitus in the absence of obesity: a risky condition.

PMID- 25378546
TI  - Body mass index and the risk of all-cause mortality among patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: Several prospective studies have evaluated the association between
      body mass index (BMI) and death risk among patients with diabetes mellitus;
      however, the results have been inconsistent. METHODS AND RESULTS: We performed a
      prospective cohort study of 19 478 black and 15 354 white patients with type 2
      diabetes mellitus. Cox proportional hazards regression models were used to
      estimate the association of different levels of BMI stratification with all-cause
      mortality. During a mean follow-up of 8.7 years, 4042 deaths were identified. The
      multivariable-adjusted (age, sex, smoking, income, and type of insurance) hazard
      ratios for all-cause mortality associated with BMI levels (18.5-22.9, 23-24.9, 25
      29.9, 30-34.9 [reference group], 35-39.9, and >=40 kg/m(2)) at baseline were 2.12
      (95% confidence interval [CI], 1.80-2.49), 1.74 (95% CI, 1.46-2.07), 1.23 (95%
      CI, 1.08-1.41), 1.00, 1.19 (95% CI, 1.03-1.39), and 1.23 (95% CI, 1.05-1.43) for
      blacks and 1.70 (95% CI, 1.42-2.04), 1.51 (95% CI, 1.27-1.80), 1.07 (95% CI, 0.94
      1.21), 1.00, 1.07 (95% CI, 0.93-1.23), and 1.20 (95% CI, 1.05-1.38) for whites,
      respectively. When stratified by age, smoking status, patient type, or the use of
      antidiabetic drugs, a U-shaped association was still present. When BMI was
      included in the Cox model as a time-dependent variable, the U-shaped association
      of BMI with all-cause mortality risk did not change. CONCLUSIONS: The present
      study indicated a U-shaped association of BMI with all-cause mortality risk among
      black and white patients with type 2 diabetes mellitus. A significantly increased
      risk of all-cause mortality was observed among blacks with BMI <30 kg/m(2) and
      >=35 kg/m(2) and among whites with BMI <25 kg/m(2) and >=40 kg/m(2) compared with
      patients with BMI of 30 to 34.9 kg/m(2).

PMID- 25378547
TI  - The value of registries for rare diseases: bacterial or mycotic aortic aneurysm.

PMID- 25378549
TI  - Creating human organs in chimaera pigs: an ethical source of immunocompatible
      organs?
AB  - New techniques in regenerative medicine may soon enable the creation of human
      organs inside animals using induced pluripotent stem cells. This technology has
      the potential to solve the organ scarcity problem by providing a limitless source
      of personalised organs for transplantation, but also raises several ethical
      issues, particularly concerning animal welfare, the 'human features' problem and
      human dignity. 

PMID- 25378548
TI  - Endovascular treatment of mycotic aortic aneurysms: a European multicenter study.
AB  - BACKGROUND: Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease.
      The aim of this European multicenter collaboration was to study the durability of
      endovascular aortic repair (EVAR) of MAA, by assessing late infection-related
      complications and long-term survival. METHODS AND RESULTS: All EVAR treated MAAs,
      between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One
      hundred twenty-three patients with 130 MAAs were identified. Mean age was 69
      years (range 39-86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47
      (38%) presented with rupture. Anatomic locations were ascending/arch (n=4),
      descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple
      (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and
      infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean
      follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were
      converted to open repair during follow-up. Survival was 91% (95% confidence
      interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%)
      after 1, 12, 60, and 120 months, respectively. Infection-related death occurred
      in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox
      regression analysis demonstrated non-Salmonella-positive culture as predictors
      for late infection-related death. CONCLUSIONS: Endovascular treatment of MAA is
      feasible and for most patients a durable treatment option. Late infections do
      occur, are often lethal, and warrant long-term antibiotic treatment and follow
      up. Patients with non-Salmonella-positive blood cultures were more likely to die
      from late infection.

PMID- 25378550
TI  - Coercion and choice in parent-child live kidney donation.
AB  - This paper explores whether donor-parents felt coerced to donate a kidney to
      their child. There is a paucity of UK literature on parental live kidney donors
      and the voluntariness of their decision-making. Data were gathered as part of a
      study exploring parental experiences of consenting for live donation at a UK
      specialist children's hospital. Parents who donated a kidney to their child
      between September 2006 and December 2010 and who consented at their child's
      hospital to be referred to an adult unit for consideration for live donation were
      invited to participate. Of the 19 eligible parents, seven fathers and three
      mothers consented to be interviewed. Their primary motivation for donation was
      being a parent (more specifically, the parent of a sick child). Participants
      expressed this in terms of parental love and concern. Participants conveyed
      certainty about their decision and viewed live donation as a positive
      opportunity. Most participants regarded the decision to donate, or not donate, as
      one every parent is entitled to make for their own reasons. In discussing our
      findings, we argue that when parents do not separate their child's interests from
      their own, this does not necessarily compromise autonomous decision-making: using
      one's own moral values to constrain one's own choices can be compatible with
      voluntary decision-making. Indeed, choices may be more constrained when parents
      are unable to donate, because this reduces the options available to parents to
      help their child. 

PMID- 25378551
TI  - Substituted judgment in real life.

PMID- 25378552
TI  - A comparison of justice frameworks for international research.
AB  - Justice frameworks have been developed for international research that provide
      guidance on the selection of research targets, ancillary care, research capacity
      strengthening, and post-trial benefits. Yet there has been limited comparison of
      the different frameworks. This paper examines the underlying aims and theoretical
      bases of three such frameworks--the fair benefits framework, the human
      development approach and research for health justice--and considers how their
      aims impact their guidance on the aforementioned four ethical issues. It shows
      that the frameworks' underlying objectives vary across two dimensions. First,
      whether they seek to prevent harmful or exploitative international research or to
      promote international research with health benefits for low and middle-income
      countries. Second, whether they address justice at the micro level or the macro
      level. The fair benefits framework focuses on reforming contractual elements in
      individual international research collaborations to ensure fairness, whereas the
      other two frameworks aim to connect international research with the reduction of
      global health inequities. The paper then highlights where there is overlap
      between the frameworks' requirements and where differences in the strength and
      content of the obligations they identify arise as a result of their varying
      objectives and theoretical bases. In doing so, it does not offer a critical
      comparison of the frameworks but rather seeks to add clarity to current debates
      on justice and international research by showing how they are positioned relative
      to one another.

PMID- 25378553
TI  - 'Neonatal' Nav1.2 reduces neuronal excitability and affects seizure
      susceptibility and behaviour.
AB  - Developmentally regulated alternative splicing produces 'neonatal' and 'adult'
      isoforms of four Na(+) channels in human brain, NaV1.1, NaV1.2, NaV1.3 and
      NaV1.6. Heterologously expressed 'neonatal' NaV1.2 channels are less excitable
      than 'adult' channels; however, functional importance of this difference is
      unknown. We hypothesized that the 'neonatal' NaV1.2 may reduce neuronal
      excitability and have a seizure-protective role during early brain development.
      To test this hypothesis, we generated NaV1.2(adult) mice expressing only the
      'adult' NaV1.2, and compared the firing properties of pyramidal cortical neurons,
      as well as seizure susceptibility, between the NaV1.2(adult) and wild-type (WT)
      mice at postnatal day 3 (P3), when the 'neonatal' isoform represents 65% of the
      WT NaV1.2. We show significant increases in action potential firing in
      NaV1.2(adult) neurons and in seizure susceptibility of NaV1.2(adult) mice,
      supporting our hypothesis. At postnatal day 15 (P15), when 17% of the WT NaV1.2
      is 'neonatal', the firing properties of NaV1.2(adult) and WT neurons converged.
      However, inhibitory postsynaptic currents in NaV1.2(adult) neurons were larger
      and the expression level of Scn2a mRNA was 24% lower compared with the WT. The
      enhanced seizure susceptibility of the NaV1.2(adult) mice persisted into adult
      age. The adult NaV1.2(adult) mice also exhibited greater risk-taking behaviour.
      Overall, our data reveal a significant impact of 'neonatal' NaV1.2 on neuronal
      excitability, seizure susceptibility and behaviour and may contribute to our
      understanding of NaV1.2 roles in health and diseases such as epilepsy and autism.

PMID- 25378554
TI  - L-leucine partially rescues translational and developmental defects associated
      with zebrafish models of Cornelia de Lange syndrome.
AB  - Cohesinopathies are human genetic disorders that include Cornelia de Lange
      syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in
      limb and craniofacial development as well as mental retardation. The
      developmental phenotypes of CdLS and other cohesinopathies suggest that mutations
      in the structure and regulation of the cohesin complex during embryogenesis
      interfere with gene regulation. In a previous project, we showed that RBS was
      associated with highly fragmented nucleoli and defects in both ribosome
      biogenesis and protein translation. l-leucine stimulation of the mTOR pathway
      partially rescued translation in human RBS cells and development in zebrafish
      models of RBS. In this study, we investigate protein translation in zebrafish
      models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E
      binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant
      embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis
      and rRNA production were decreased in the cohesin morphant embryo cells. l
      leucine partly rescued protein synthesis and rRNA production in the cohesin
      morphants and partially restored phosphorylation of RPS6 and 4EBP1.
      Concomitantly, l-leucine treatment partially improved cohesinopathy embryo
      development including the formation of craniofacial cartilage. Interestingly, we
      observed that alpha-ketoisocaproate (alpha-KIC), which is a keto derivative of
      leucine, also partially rescued the development of rad21 and nipbla/b morphants
      by boosting mTOR-dependent translation. In summary, our results suggest that
      cohesinopathies are caused in part by defective protein synthesis, and
      stimulation of the mTOR pathway through l-leucine or its metabolite alpha-KIC can
      partially rescue development in zebrafish models for CdLS. 

PMID- 25378556
TI  - Nuclear TDP-43 causes neuronal toxicity by escaping from the inhibitory
      regulation by hnRNPs.
AB  - Dysregulation of transactive response DNA-binding protein-43 (TDP-43) is thought
      to be linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and
      frontotemporal lobar degeneration (FTLD). TDP-43 normally localizes in the
      nucleus but its main localization shifts to the cytoplasm in most affected cells
      of ALS and FTLD patients. It is not yet known whether nuclear or cytoplasmic TDP
      43 is responsible for TDP-43-induced neurotoxicity. In this study, we show that
      nuclear TDP-43 causes TDP-43 neurotoxicity. DNA/RNA-binding and dimerization of
      TDP-43 are both essential for TDP-43-induced cell death. Moreover, endogenous
      heterogeneous nuclear ribonucleoprotein-U (hnRNP-U) binds to TDP-43 and knocking
      down of hnRNP-U induces neurotoxicity, whereas overexpression of hnRNP-U or hnRNP
      A2 inhibits TDP-43-induced neurotoxicity. In addition, hnRNP-U inhibits TDP-43
      mediated alterations in splicing of POLDIP3 mRNA. Altogether, these results
      suggest that nuclear TDP-43 becomes neurotoxic by escaping from the inhibitory
      regulation by hnRNPs. 

PMID- 25378555
TI  - Whole-genome sequencing to understand the genetic architecture of common gene
      expression and biomarker phenotypes.
AB  - Initial results from sequencing studies suggest that there are relatively few low
      frequency (<5%) variants associated with large effects on common phenotypes. We
      performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI
      study to test two primary hypotheses: (i) that sequencing would detect single low
      frequency-large effect variants that explained similar amounts of phenotypic
      variance as single common variants, and (ii) that some common variant
      associations could be explained by low-frequency variants. We tested two sets of
      disease-related common phenotypes for which we had statistical power to detect
      large numbers of common variant-common phenotype associations-11 132 cis-gene
      expression traits in 450 individuals and 93 circulating biomarkers in all 680
      individuals. From a total of 11 657 229 high-quality variants of which 6 129 221
      and 5 528 008 were common and low frequency (<5%), respectively, low frequency
      large effect associations comprised 7% of detectable cis-gene expression traits
      [89 of 1314 cis-eQTLs at P < 1 * 10(-06) (false discovery rate ~5%)] and one of
      eight biomarker associations at P < 8 * 10(-10). Very few (30 of 1232; 2%) common
      variant associations were fully explained by low-frequency variants. Our data
      show that whole-genome sequencing can identify low-frequency variants undetected
      by genotyping based approaches when sample sizes are sufficiently large to detect
      substantial numbers of common variant associations, and that common variant
      associations are rarely explained by single low-frequency variants of large
      effect. 

PMID- 25378558
TI  - Thinking regionally: narrative, the medical humanities and region.
AB  - Drawing on multiple literatures from history, geography, anthropology, sociology
      and literature, this essay asks questions about what we mean by region and why
      narratives of region should matter to the medical humanities. The essay surveys
      how region can be used as a lens of analysis, exploring the various academic
      approaches to region and their limitations. It argues that regions are dynamic
      but also unstable as a category of analysis and are often used uncritically by
      scholars. In encouraging scholars working in the medical humanities to be aware
      that regions are not simple objective or analytical boxes, the essay shows how an
      awareness of region helps challenge metropolitan whiggism and ideas of core and
      periphery to give a more prominent place to hinterlands, market towns and rural
      environments. Furthermore, the essay considers how incorporating region into our
      understanding of illness can offer new insights. It demonstrates the need for
      scholars to be attuned to the narratives constructed around regions, suggesting
      that regions can be viewed as discursive formations that provide a frame for
      understanding both collective and personal ideas of, and responses to, health and
      illness, disease and healing, to create what Megan Davies calls a more nuanced
      'intellectual cartography'. 

PMID- 25378559
TI  - Integrating plant hydraulics and gas exchange along the drought-response trait
      spectrum.

PMID- 25378560
TI  - Anabaena cell ageing monitored with confocal fluorescence spectroscopy.
AB  - Cyanobacteria use a sophisticated system of pigments to collect light energy
      across the visible spectrum for photosynthesis. The pigments are assembled in
      structures called phycobilisomes, composed of phycoerythrocyanin, phycocyanin and
      allophycocyanin, which absorb energy and transfer it to chlorophyll in
      photosystem II reaction centres. All of the components of this system are
      fluorescent, allowing sensitive measurements of energy transfer using single cell
      confocal fluorescence microscopy. The native pigments can be interrogated without
      the use of reporters. Here, we use confocal fluorescence microscopy to monitor
      changes in the efficiency of energy transfer as single cells age, between the
      time they are born at cell division until they are ready to divide again.
      Alteration of fluorescence was demonstrated to change with the age of the
      cyanobacterial cell. 

PMID- 25378561
TI  - Type II toxin-antitoxin systems are unevenly distributed among Escherichia coli
      phylogroups.
AB  - Type II toxin-antitoxin systems (TAs) are bicistronic operons ubiquitous in
      prokaryotic genomes, displaying multilevel association with cell physiology.
      Various possible functions have been assigned to TAs, ranging from beneficial for
      their hosts, such as a stress response, dormancy and protection against genomic
      parasites, to detrimental or useless functions, such as selfish alleles. As there
      is a link between several Escherichia coli features (e.g. virulence, lifestyle)
      and the phylogeny of this species, we hypothesized a similar association with
      TAs. Using PCR we studied the distribution of 15 chromosomal and plasmidic type
      II TA loci in 84 clinical E. coli isolates in relation to their main phylogenetic
      groups (A, B1, B2 and D). In addition, we performed in silico searching of these
      TA loci in 60 completely sequenced E. coli genomes deposited in GenBank. The
      highest number of TA loci per strain was observed in group A (mean 8.2, range 5
      12) and the lowest in group B2 (mean 4.2, range 2-8). Moreover, significant
      differences in the prevalence of nine chromosomal TAs among E. coli phylogroups
      were noted. In conclusion, the presence of some chromosomal TAs in E. coli is
      phylogroup-related rather than a universal feature of the species. In addition,
      their limited collection in group B2 clearly distinguish it from the other E.
      coli phylogroups. 

PMID- 25378562
TI  - Vsl1p cooperates with Fsv1p for vacuolar protein transport and homotypic fusion
      in Schizosaccharomyces pombe.
AB  - Members of the SNARE protein family participate in the docking-fusion step of
      several intracellular vesicular transport events. Saccharomyces cerevisiae Vam7p
      was identified as a SNARE protein that acts in vacuolar protein transport and
      membrane fusion. However, in Schizosaccharomyces pombe, there have been no
      reports regarding the counterpart of Vam7p. Here, we found that, although the
      SPCC594.06c gene has low similarity to Vam7p, the product of SPCC594.06c has a PX
      domain and SNARE motif like Vam7p, and thus we designated the gene Sch. pombe
      vsl1(+) (Vam7-like protein 1). The vsl1Delta cells showed no obvious defect in
      vacuolar protein transport. However, cells of the vsl1Delta mutant with a
      deletion of fsv1(+), which encodes another SNARE protein, displayed extreme
      defects in vacuolar protein transport and vacuolar morphology. Vsl1p was
      localized to the vacuolar membrane and prevacuolar compartment, and its PX domain
      was essential for proper localization. Expression of the fusion protein GFP-Vsl1p
      was able to suppress ZnCl2 sensitivity and the vacuolar protein sorting defect in
      the fsv1Delta cells. Moreover, GFP-Vsl1p was mislocalized in a pep12Delta mutant
      and in cells overexpressing fsv1(+). Importantly, overexpression of Sac.
      cerevisiae VAM7 could suppress the sensitivity to ZnCl2 of vsl1Delta cells and
      the vacuolar morphology defect of vsl1Deltafsv1Delta cells in Sch. pombe. Taken
      together, these data suggest that Vsl1p and Fsv1p are required for vacuolar
      protein transport and membrane fusion, and they function cooperatively with
      Pep12p in the same membrane-trafficking step. 

PMID- 25378564
TI  - No more Mr Nasty.

PMID- 25378563
TI  - The antibacterial properties of isothiocyanates.
AB  - Isothiocyanates (ITCs) are natural plant products generated by the enzymic
      hydrolysis of glucosinolates found in Brassicaceae vegetables. These natural
      sulfur compounds and their dithiocarbamate conjugates have been previously
      evaluated for their anti-cancerous properties. Their antimicrobial properties
      have been previously studied as well, mainly for food preservation and plant
      pathogen control. Recently, several revelations concerning the mode of action of
      ITCs in prokaryotes have emerged. This review addresses these new studies and
      proposes a model to summarize the current knowledge and hypotheses for the
      antibacterial effect of ITCs and whether they may provide the basis for the
      design of novel antibiotics. 

PMID- 25378567
TI  - Neutralization activity of patient sera collected during the 2008-2009
      Chikungunya outbreak in Thailand.
AB  - Chikungunya virus (CHIKV) infection typically causes fever, rash, myalgia, and
      arthralgia and sometimes results in recurrent joint pain or, in severe cases,
      neurological disorders or death. How CHIKV infection leads to prolonged or severe
      symptoms is still not well understood. In this study, we examined the
      neutralization (NT) titer of 98 serum samples collected from patients during the
      2008-2009 chikungunya outbreak in Thailand. While all serum samples showed
      neutralizing activity, virus was detected in 58% of the serum samples. When we
      analyzed a possible association between virus and antibody titers and the
      presence of typical symptoms of CHIKV infection, fever and joint pain, there was
      no significant association except that the number of patients with fever was over
      three times more than the number of those without fever when CHIKV was detectable
      in serum. This study indicates that although neutralizing antibody is critical to
      eliminate CHIKV, it appears not to be the main factor associated with clinical
      symptoms in some cases, so that other aspects of immune responses, such as those
      involving proinflammatory mediators and adaptive immune cells, should be
      considered altogether. 

PMID- 25378568
TI  - Laboratory evaluation of a dual rapid immunodiagnostic test for HIV and syphilis
      infection.
AB  - New dual tests for HIV and syphilis have been developed. Our study aimed to
      evaluate the laboratory performance of a dual rapid immunodiagnostic test for HIV
      and syphilis. Our evaluation showed high performance of this dual rapid test,
      which should be considered for implementation to increase screening coverage and
      efficiency. 

PMID- 25378569
TI  - Evaluating the Auto-MODS assay, a novel tool for tuberculosis diagnosis for use
      in resource-limited settings.
AB  - There is an urgent need for simple, rapid, and affordable diagnostic tests for
      tuberculosis (TB) to combat the great burden of the disease in developing
      countries. The microscopic observation drug susceptibility assay (MODS) is a
      promising tool to fill this need, but it is not widely used due to concerns
      regarding its biosafety and efficiency. This study evaluated the automated MODS
      (Auto-MODS), which operates on principles similar to those of MODS but with
      several key modifications, making it an appealing alternative to MODS in resource
      limited settings. In the operational setting of Chiang Rai, Thailand, we compared
      the performance of Auto-MODS with the gold standard liquid culture method in
      Thailand, mycobacterial growth indicator tube (MGIT) 960 plus the SD Bioline TB
      Ag MPT64 test, in terms of accuracy and efficiency in differentiating TB and non
      TB samples as well as distinguishing TB and multidrug-resistant (MDR) TB samples.
      Sputum samples from clinically diagnosed TB and non-TB subjects across 17
      hospitals in Chiang Rai were consecutively collected from May 2011 to September
      2012. A total of 360 samples were available for evaluation, of which 221 (61.4%)
      were positive and 139 (38.6%) were negative for mycobacterial cultures according
      to MGIT 960. Of the 221 true-positive samples, Auto-MODS identified 212 as
      positive and 9 as negative (sensitivity, 95.9%; 95% confidence interval [CI],
      92.4% to 98.1%). Of the 139 true-negative samples, Auto-MODS identified 135 as
      negative and 4 as positive (specificity, 97.1%; 95% CI, 92.8% to 99.2%). The
      median time to culture positivity was 10 days, with an interquartile range of 8
      to 13 days for Auto-MODS. Auto-MODS is an effective and cost-sensitive
      alternative diagnostic tool for TB diagnosis in resource-limited settings. 

PMID- 25378570
TI  - Streamlining HIV testing for HIV preexposure prophylaxis.
AB  - HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to
      minimize the risk of drug resistance, the time off PrEP required to evaluate
      false-positive screening results, and costs and to expedite the start of therapy
      for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies
      provide results in less than 1 h and can be conducted by nonlicensed staff at the
      point of care. In many regions, Western blot (WB) testing is required to confirm
      reactive RT results. WB testing, however, causes delays in diagnosis and adds
      expense. The iPrEx study evaluated the safety and efficacy of daily oral
      emtricitabine-tenofovir disoproxil fumarate among HIV-seronegative men and
      transgender women who have sex with men: HIV infection was assessed with two RTs
      plus WB confirmation, followed by HIV-1 plasma viral load testing. During the
      iPrEx study, there were 51,260 HIV status evaluations among 2,499 volunteers
      using RTs: 142 (0.28%) had concordant positive results (100% were eventually
      confirmed) and 19 (0.04%) had discordant results among 14 participants; 11 were
      eventually determined to be HIV infected. A streamlined approach using only one
      RT to screen and a second RT to confirm (without WB) would have had nearly the
      same accuracy. Discrepant RT results are best evaluated with nucleic acid
      testing, which would also increase sensitivity. 

PMID- 25378571
TI  - Comparison of Etest, disk diffusion, and broth macrodilution for in vitro
      susceptibility testing of Rhodococcus equi.
AB  - MICs of erythromycin, clarithromycin, azithromycin, rifampin, gentamicin, and
      doxycycline against 101 isolates of Rhodococcus equi were determined by broth
      macrodilution, disk diffusion, and Etest. Categorical agreement ranged between
      85.1 and 100%. Overall, the agreement between Etest and disk diffusion was better
      than the agreement between broth macrodilution and the agar-based methods. 

PMID- 25378572
TI  - Clinical outcomes of Enterobacteriaceae infections stratified by carbapenem MICs.
AB  - The Clinical and Laboratory Standards Institute (CLSI) lowered the MIC
      breakpoints for meropenem and imipenem from 4 mg/liter to 1 mg/liter for
      Enterobacteriaceae in 2010. The breakpoint change improves the probability of
      pharmacodynamic target attainment and eliminates the need for microbiology labs
      to perform confirmatory testing for Klebsiella pneumoniae carbapenemase (KPC)
      production or other beta-lactamases that hydrolyze carbapenems. However, there
      are limited data evaluating clinical outcomes of the affected breakpoints, and it
      is unknown if patients infected with Enterobacteriaceae with reduced
      susceptibility are more likely to have poor outcomes when treated with a
      carbapenem. We conducted a single-center retrospective matched-cohort analysis in
      adult patients with Enterobacteriaceae infections treated with meropenem,
      imipenem, or doripenem. Patients with Enterobacteriaceae infection with a
      carbapenem MIC of 2 to 8 mg/liter were matched based on pathogen, source of
      infection, comorbidities, and disease severity (1:1 ratio) to those with a
      carbapenem MIC of <=1 mg/liter. A total of 36 patients were included in the
      study. The group with carbapenem MICs of 2 to 8 mg/liter had a significantly
      higher 30-day mortality than the group with carbapenem MICs of <=1 mg/liter
      (38.9% compared to 5.6%, P = 0.04). Total hospital length of stay (LOS) and
      intensive care unit (ICU) LOS were longer in the group with MICs of 2 to 8
      mg/liter than in the group with MICs of <=1 mg/liter (57.6 days compared to 34.4
      days [P = 0.06] and 56.6 days compared to 21.7 days [P < 0.01], respectively).
      Patients infected with Enterobacteriaceae with a carbapenem MIC of 2, 4, or 8
      mg/liter had higher mortality rates and longer ICU LOS than matched cohorts with
      carbapenem MICs of <=1 mg/liter, which supports CLSI's recommendation to lower
      susceptibility breakpoints for carbapenems. 

PMID- 25378557
TI  - Fine-mapping of the HNF1B multicancer locus identifies candidate variants that
      mediate endometrial cancer risk.
AB  - Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are
      associated with the risk of Type II diabetes and multiple cancers. Evidence to
      date indicates that cancer risk may be mediated via genetic or epigenetic effects
      on HNF1B gene expression. We previously found single-nucleotide polymorphisms
      (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now
      report extensive fine-mapping and in silico and laboratory analyses of this
      locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37
      925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of
      association for SNP rs11263763 (P = 8.4 * 10(-14), odds ratio = 0.86, 95%
      confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype
      analysis and conditional analyses provide no evidence of further independent
      endometrial cancer risk variants at this locus. SNP rs11263763 genotype was
      associated with HNF1B mRNA expression but not with HNF1B methylation in
      endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses
      prioritized rs11263763 and four other SNPs in high-to-moderate linkage
      disequilibrium as the most likely causal SNPs. Three of these SNPs map to the
      extended HNF1B promoter based on chromatin marks extending from the minimal
      promoter region. Reporter assays demonstrated that this extended region reduces
      activity in combination with the minimal HNF1B promoter, and that the minor
      alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter
      activity. Our findings provide evidence for a single signal associated with
      endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via
      altered HNF1B gene expression. 

PMID- 25378575
TI  - Detection of intracellular parasites by use of the CellaVision DM96 analyzer
      during routine screening of peripheral blood smears.
AB  - Conventional microscopy is the gold standard for malaria diagnosis. The
      CellaVision DM96 is a digital hematology analyzer that utilizes neural networks
      to locate, digitize, and preclassify leukocytes and characterize red blood cell
      morphology. This study compared the detection rates of Plasmodium and Babesia
      species on peripheral blood smears utilizing the CellaVision DM96 with the rates
      for a routine red blood cell morphology scan. A total of 281 slides were
      analyzed, consisting of 130 slides positive for Plasmodium or Babesia species and
      151 negative controls. Slides were blinded, randomized, and analyzed by
      CellaVision and microscopy for red cell morphology scans. The technologists were
      blinded to prior identification results. The parasite detection rate was 73%
      (95/130) for CellaVision and 81% (105/130) for microscopy for positive samples.
      The interobserver agreement between CellaVision and microscopy was fair, as
      Cohen's kappa coefficient equaled 0.36. Pathologist review of CellaVision images
      identified an additional 15 slides with parasites, bringing the total number of
      detectable positive slides to 110 of 130 (85%). Plasmodium ovale had the lowest
      rate of detection at 56% (5 of 9); Plasmodium malariae and Babesia spp. had the
      highest rate of detection at 100% (3/3 and 6/6, respectively). The detection rate
      by CellaVision was 100% (23/23) when the parasitemia was >=2.5%. The detection
      rate for <0.1% parasitemia was 63% (15/24). Technologists appropriately
      classified all negative specimens. The percentage of positive specimens
      detectable by CellaVision (73%) approaches results for microscopy on routine scan
      of peripheral blood smears for red blood cell morphology. 

PMID- 25378573
TI  - Whole-genome phylogenomic heterogeneity of Neisseria gonorrhoeae isolates with
      decreased cephalosporin susceptibility collected in Canada between 1989 and 2013.
AB  - A large-scale, whole-genome comparison of Canadian Neisseria gonorrhoeae isolates
      with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology
      approach to investigate strain relatedness and dynamics. Although current typing
      methods have been very successful in tracing short-chain transmission of
      gonorrheal disease, investigating the temporal evolutionary relationships and
      geographical dissemination of highly clonal lineages requires enhanced resolution
      only available through whole-genome sequencing (WGS). Phylogenomic cluster
      analysis grouped 169 Canadian strains into 12 distinct clades. While some N.
      gonorrhoeae multiantigen sequence types (NG-MAST) agreed with specific
      phylogenomic clades or subclades, other sequence types (ST) and closely related
      groups of ST were widely distributed among clades. Decreased susceptibility to
      extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse
      strains in Canada during the 1990s with a variety of nonmosaic penA alleles,
      followed in 2000/2001 with the penA mosaic X allele and then in 2007 with ST1407
      strains with the penA mosaic XXXIV allele. Five genetically distinct ESC-DS
      lineages were associated with penA mosaic X, XXXV, and XXXIV alleles and
      nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was
      observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs
      associated with WGS decline and analysis tools are streamlined, WGS can provide a
      more thorough understanding of strain dynamics, facilitate epidemiological
      studies to better resolve social networks, and improve surveillance to optimize
      treatment for gonorrheal infections. 

PMID- 25378574
TI  - High-resolution hepatitis C virus subtyping using NS5B deep sequencing and
      phylogeny, an alternative to current methods.
AB  - Hepatitis C virus (HCV) is classified into seven major genotypes and 67 subtypes.
      Recent studies have shown that in HCV genotype 1-infected patients, response
      rates to regimens containing direct-acting antivirals (DAAs) are subtype
      dependent. Currently available genotyping methods have limited subtyping
      accuracy. We have evaluated the performance of a deep-sequencing-based HCV
      subtyping assay, developed for the 454/GS-Junior platform, in comparison with
      those of two commercial assays (Versant HCV genotype 2.0 and Abbott Real-time HCV
      Genotype II) and using direct NS5B sequencing as a gold standard (direct
      sequencing), in 114 clinical specimens previously tested by first-generation
      hybridization assay (82 genotype 1 and 32 with uninterpretable results).
      Phylogenetic analysis of deep-sequencing reads matched subtype 1 calling by
      population Sanger sequencing (69% 1b, 31% 1a) in 81 specimens and identified a
      mixed-subtype infection (1b/3a/1a) in one sample. Similarly, among the 32
      previously indeterminate specimens, identical genotype and subtype results were
      obtained by direct and deep sequencing in all but four samples with dual
      infection. In contrast, both Versant HCV Genotype 2.0 and Abbott Real-time HCV
      Genotype II failed subtype 1 calling in 13 (16%) samples each and were unable to
      identify the HCV genotype and/or subtype in more than half of the non-genotype 1
      samples. We concluded that deep sequencing is more efficient for HCV subtyping
      than currently available methods and allows qualitative identification of mixed
      infections and may be more helpful with respect to informing treatment strategies
      with new DAA-containing regimens across all HCV subtypes. 

PMID- 25378576
TI  - Comparative analysis of subtyping methods against a whole-genome-sequencing
      standard for Salmonella enterica serotype Enteritidis.
AB  - A retrospective investigation was performed to evaluate whole-genome sequencing
      as a benchmark for comparing molecular subtyping methods for Salmonella enterica
      serotype Enteritidis and survey the population structure of commonly encountered
      S. enterica serotype Enteritidis outbreak isolates in the United States. A total
      of 52 S. enterica serotype Enteritidis isolates representing 16 major outbreaks
      and three sporadic cases collected between 2001 and 2012 were sequenced and
      subjected to subtyping by four different methods: (i) whole-genome single
      nucleotide-polymorphism typing (WGST), (ii) multiple-locus variable-number tandem
      repeat (VNTR) analysis (MLVA), (iii) clustered regularly interspaced short
      palindromic repeats combined with multi-virulence-locus sequence typing (CRISPR
      MVLST), and (iv) pulsed-field gel electrophoresis (PFGE). WGST resolved all
      outbreak clusters and provided useful robust phylogenetic inference results with
      high epidemiological correlation. While both MLVA and CRISPR-MVLST yielded higher
      discriminatory power than PFGE, MLVA outperformed the other methods in
      delineating outbreak clusters whereas CRISPR-MVLST showed the potential to trace
      major lineages and ecological origins of S. enterica serotype Enteritidis. Our
      results suggested that whole-genome sequencing makes a viable platform for the
      evaluation and benchmarking of molecular subtyping methods. 

PMID- 25378577
TI  - Clinical isolates of Salmonella enterica serovar Agona producing NDM-1 metallo
      beta-lactamase: first report from Pakistan.
AB  - We report two cases of infantile diarrhea due to multidrug-resistant, NDM-1
      metallo-beta-lactamase-producing Salmonella enterica serovar Agona from Pakistan.
      This study alerts toward possible risk of NDM-1 transmission to enteric fever
      pathogens and encourages microbiologists to consider active screening of
      carbapenem resistance in nontyphoidal Salmonella isolates. 

PMID- 25378578
TI  - Utility of measuring (1,3)-beta-d-glucan in cerebrospinal fluid for diagnosis of
      fungal central nervous system infection.
AB  - (1-3)-beta-d-Glucan (BDG) from cerebrospinal fluid (CSF) is a promising marker
      for diagnostic and prognostic aid of central nervous system (CNS) fungal
      infection, but its relationship to serum values has not been studied. Herein, we
      detected BDG from CSF at levels 2-fold lower than those in serum in patients
      without evidence of fungal disease but 25-fold higher than those in in serum in
      noncryptococcal CNS fungal infections. CSF BDG may be a useful biomarker in the
      evaluation of fungal CNS disease. 

PMID- 25378579
TI  - Kinetics of poliovirus shedding following oral vaccination as measured by
      quantitative reverse transcription-PCR versus culture.
AB  - Amid polio eradication efforts, detection of oral polio vaccine (OPV) virus in
      stool samples can provide information about rates of mucosal immunity and allow
      estimation of the poliovirus reservoir. We developed a multiplex one-step
      quantitative reverse transcription-PCR (qRT-PCR) assay for detection of OPV Sabin
      strains 1, 2, and 3 directly in stool samples with an external control to
      normalize samples for viral quantity and compared its performance with that of
      viral culture. We applied the assay to samples from infants in Dhaka, Bangladesh,
      after the administration of trivalent OPV (tOPV) at weeks 14 and 52 of life (on
      days 0 [pre-OPV], +4, +11, +18, and +25 relative to vaccination). When 1,350
      stool samples were tested, the sensitivity and specificity of the quantitative
      PCR (qPCR) assay were 89 and 91% compared with culture. A quantitative
      relationship between culture(+)/qPCR(+) and culture(-)/qPCR(+) stool samples was
      observed. The kinetics of shedding revealed by qPCR and culture were similar.
      qPCR quantitative cutoffs based on the day +11 or +18 stool samples could be used
      to identify the culture-positive shedders, as well as the long-duration or high
      frequency shedders. Interestingly, qPCR revealed that a small minority (7%) of
      infants contributed the vast majority (93 to 100%) of the total estimated viral
      excretion across all subtypes at each time point. This qPCR assay for OPV can
      simply and quantitatively detect all three Sabin strains directly in stool
      samples to approximate shedding both qualitatively and quantitatively. 

PMID- 25378580
TI  - miR168 influences phase transition, leaf epinasty, and fruit development via
      SlAGO1s in tomato.
AB  - In Arabidopsis thaliana, Argonaute1 (AGO1) interacts with miR168 to modulate the
      small RNA regulatory pathway. However, the underlying mechanism of regulation and
      relationship between AGO1 and miR168 is poorly understood in the cash crop
      Solanum lycopersicum (tomato). We previously found that SlAGO1A and SlAGO1B were
      cleaved by miR168 in tomato. In this study, we show that SlAGO1A and SlAGO1B
      accumulate in miR168-sponge transgenic plants, and that expression of miR168
      resistant SlAGO1A (4m-SlAGO1A) and SlAGO1B (4m-SlAGO1B) in tomato results in a
      series of defects affecting growth rate, floral timing, leaves, and fruit.
      Accumulation of miR156 was found when 4m-SlAGO1A was at an early developmental
      stage compared to the wild type and original SlAGO1A transgenic plants, and
      miR172 was highly expressed in adult 4m-SlAGO1A compared to the controls. In
      addition, the expression of multiple small RNAs was altered in 4m-SlAGO1A. Taken
      together, our data provide novel insights into the interaction between SlAGO1s
      and miR168 in determining growth rate, phase change, leaf epinasty, fruit
      initiation and expansion, and other developmental processes in tomato.

PMID- 25378581
TI  - KIF5B transports BNIP-2 to regulate p38 mitogen-activated protein kinase
      activation and myoblast differentiation.
AB  - The Cdo-p38MAPK (p38 mitogen-activated protein kinase) signaling pathway plays
      important roles in regulating skeletal myogenesis. During myogenic
      differentiation, the cell surface receptor Cdo bridges scaffold proteins BNIP-2
      and JLP and activates p38MAPK, but the spatial-temporal regulation of this
      process is largely unknown. We here report that KIF5B, the heavy chain of kinesin
      1 motor, is a novel interacting partner of BNIP-2. Coimmunoprecipitation and far
      Western study revealed that BNIP-2 directly interacted with the motor and tail
      domains of KIF5B via its BCH domain. By using a range of organelle markers and
      live microscopy, we determined the endosomal localization of BNIP-2 and revealed
      the microtubule-dependent anterograde transport of BNIP-2 in C2C12 cells. The
      anterograde transport of BNIP-2 was disrupted by a dominant-negative mutant of
      KIF5B. In addition, knockdown of KIF5B causes aberrant aggregation of BNIP-2,
      confirming that KIF5B is critical for the anterograde transport of BNIP-2 in
      cells. Gain- and loss-of-function experiments further showed that KIF5B modulates
      p38MAPK activity and in turn promotes myogenic differentiation. Of importance,
      the KIF5B-dependent anterograde transport of BNIP-2 is critical for its
      promyogenic effects. Our data reveal a novel role of KIF5B in the spatial
      regulation of Cdo-BNIP-2-p38MAPK signaling and disclose a previously
      unappreciated linkage between the intracellular transporting system and
      myogenesis regulation. 

PMID- 25378582
TI  - A novel mechanism for the establishment of sister chromatid cohesion by the ECO1
      acetyltransferase.
AB  - Cohesin complex mediates cohesion between sister chromatids, which promotes high
      fidelity chromosome segregation. Eco1p acetylates the cohesin subunit Smc3p
      during S phase to establish cohesion. The current model posits that this Eco1p
      mediated acetylation promotes establishment by abrogating the ability of Wpl1p to
      destabilize cohesin binding to chromosomes. Here we present data from budding
      yeast that is incompatible with this Wpl1p-centric model. Two independent in vivo
      assays show that a wpl1? fails to suppress cohesion defects of eco1? cells.
      Moreover, a wpl1? also fails to suppress cohesion defects engendered by blocking
      just the essential Eco1p acetylation sites on Smc3p (K112, K113). Thus removing
      WPL1 inhibition is insufficient for generating cohesion without ECO1 activity. To
      elucidate how ECO1 promotes cohesion, we conducted a genetic screen and
      identified a cohesion activator mutation in the SMC3 head domain (D1189H). Smc3
      D1189H partially restores cohesion in eco1? wpl1? or eco1 mutant cells but
      robustly restores cohesion in cells blocked for Smc3p K112 K113 acetylation.
      These data support two important conclusions. First, acetylation of the K112 K113
      region by Eco1p promotes cohesion establishment by altering Smc3p head function
      independent of its ability to antagonize Wpl1p. Second, Eco1p targets other than
      Smc3p K112 K113 are necessary for efficient establishment. 

PMID- 25378583
TI  - FRET detection of lymphocyte function-associated antigen-1 conformational
      extension.
AB  - Lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18, alphaLbeta2
      integrin) and its ligands are essential for adhesion between T-cells and antigen
      presenting cells, formation of the immunological synapse, and other immune cell
      interactions. LFA-1 function is regulated through conformational changes that
      include the modulation of ligand binding affinity and molecular extension.
      However, the relationship between molecular conformation and function is unclear.
      Here fluorescence resonance energy transfer (FRET) with new LFA-1-specific
      fluorescent probes showed that triggering of the pathway used for T-cell
      activation induced rapid unquenching of the FRET signal consistent with extension
      of the molecule. Analysis of the FRET quenching at rest revealed an unexpected
      result that can be interpreted as a previously unknown LFA-1 conformation. 

PMID- 25378584
TI  - Polarized sorting of the copper transporter ATP7B in neurons mediated by
      recognition of a dileucine signal by AP-1.
AB  - Neurons are highly polarized cells having distinct somatodendritic and axonal
      domains. Here we report that polarized sorting of the Cu(2+) transporter ATP7B
      and the vesicle-SNARE VAMP4 to the somatodendritic domain of rat hippocampal
      neurons is mediated by recognition of dileucine-based signals in the cytosolic
      domains of the proteins by the sigma1 subunit of the clathrin adaptor AP-1. Under
      basal Cu(2+) conditions, ATP7B was localized to the trans-Golgi network (TGN) and
      the plasma membrane of the soma and dendrites but not the axon. Mutation of a
      dileucine-based signal in ATP7B or overexpression of a dominant-negative sigma1
      mutant resulted in nonpolarized distribution of ATP7B between the somatodendritic
      and axonal domains. Furthermore, addition of high Cu(2+) concentrations,
      previously shown to reduce ATP7B incorporation into AP-1-containing clathrin
      coated vesicles, caused loss of TGN localization and somatodendritic polarity of
      ATP7B. These findings support the notion of AP-1 as an effector of polarized
      sorting in neurons and suggest that altered polarity of ATP7B in polarized cell
      types might contribute to abnormal copper metabolism in the MEDNIK syndrome, a
      neurocutaneous disorder caused by mutations in the sigma1A subunit isoform of AP
      1. 

PMID- 25378585
TI  - Plasma membrane aminoglycerolipid flippase function is required for signaling
      competence in the yeast mating pheromone response pathway.
AB  - The class 4 P-type ATPases ("flippases") maintain membrane asymmetry by
      translocating phosphatidylethanolamine and phosphatidylserine from the outer
      leaflet to the cytosolic leaflet of the plasma membrane. In Saccharomyces
      cerevisiae, five related gene products (Dnf1, Dnf2, Dnf3, Drs2, and Neo1) are
      implicated in flipping of phosphatidylethanolamine, phosphatidylserine, and
      phosphatidylcholine. In MAT A: cells responding to alpha-factor, we found that
      Dnf1, Dnf2, and Dnf3, as well as the flippase-activating protein kinase Fpk1,
      localize at the projection ("shmoo") tip where polarized growth is occurring and
      where Ste5 (the central scaffold protein of the pheromone-initiated MAPK cascade)
      is recruited. Although viable, a MAT A: dnf1? dnf2? dnf3? triple mutant exhibited
      a marked decrease in its ability to respond to alpha-factor, which we could
      attribute to pronounced reduction in Ste5 stability resulting from an elevated
      rate of its Cln2?Cdc28-initiated degradation. Similarly, a MAT A: dnf1? dnf3?
      drs2? triple mutant also displayed marked reduction in its ability to respond to
      alpha-factor, which we could attribute to inefficient recruitment of Ste5 to the
      plasma membrane due to severe mislocalization of the cellular
      phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate pools.
      Thus proper remodeling of plasma membrane aminoglycerolipids and
      phosphoinositides is necessary for efficient recruitment, stability, and function
      of the pheromone signaling apparatus. 

PMID- 25378586
TI  - The ubiquitin-conjugating enzyme UBE2E3 and its import receptor importin-11
      regulate the localization and activity of the antioxidant transcription factor
      NRF2.
AB  - The transcription factor NF-E2 p45-related factor (Nrf2) induces the expression
      of cytoprotective proteins that maintain and restore redox homeostasis. Nrf2
      levels and activity are tightly regulated, and three subcellular populations of
      the transcription factor have been identified. During homeostasis, the majority
      of Nrf2 is degraded in the cytoplasm by ubiquitin (Ub)-mediated degradation. A
      second population is transcriptionally active in the nucleus, and a third
      population localizes to the outer mitochondrial membrane. Still unresolved are
      the mechanisms and factors that govern Nrf2 distribution between its subcellular
      locales. We show here that the Ub-conjugating enzyme UBE2E3 and its nuclear
      import receptor importin 11 (Imp-11) regulate Nrf2 distribution and activity.
      Knockdown of UBE2E3 reduces nuclear Nrf2, decreases Nrf2 target gene expression,
      and relocalizes the transcription factor to a perinuclear cluster of
      mitochondria. In a complementary manner, Imp-11 functions to restrict KEAP1, the
      major suppressor of Nrf2, from prematurely extracting the transcription factor
      off of a subset of target gene promoters. These findings identify a novel pathway
      of Nrf2 modulation during homeostasis and support a model in which UBE2E3 and Imp
      11 promote Nrf2 transcriptional activity by restricting the transcription factor
      from partitioning to the mitochondria and limiting the repressive activity of
      nuclear KEAP1. 

PMID- 25378587
TI  - Cholesterol-mediated activation of acid sphingomyelinase disrupts autophagy in
      the retinal pigment epithelium.
AB  - Autophagy is an essential mechanism for clearing damaged organelles and proteins
      within the cell. As with neurodegenerative diseases, dysfunctional autophagy
      could contribute to blinding diseases such as macular degeneration. However,
      precisely how inefficient autophagy promotes retinal damage is unclear. In this
      study, we investigate innate mechanisms that modulate autophagy in the retinal
      pigment epithelium (RPE), a key site of insult in macular degeneration. High
      speed live imaging of polarized adult primary RPE cells and data from a mouse
      model of early-onset macular degeneration identify a mechanism by which
      lipofuscin bisretinoids, visual cycle metabolites that progressively accumulate
      in the RPE, disrupt autophagy. We demonstrate that bisretinoids trap cholesterol
      and bis(monoacylglycero)phosphate, an acid sphingomyelinase (ASMase) cofactor,
      within the RPE. ASMase activation increases cellular ceramide, which promotes
      tubulin acetylation on stabilized microtubules. Live-imaging data show that
      autophagosome traffic and autophagic flux are inhibited in RPE with acetylated
      microtubules. Drugs that remove excess cholesterol or inhibit ASMase reverse this
      cascade of events and restore autophagosome motility and autophagic flux in the
      RPE. Because accumulation of lipofuscin bisretinoids and abnormal cholesterol
      homeostasis are implicated in macular degeneration, our studies suggest that
      ASMase could be a potential therapeutic target to ensure the efficient autophagy
      that maintains RPE health. 

PMID- 25378589
TI  - Haemodialysis adequacy monitoring for phosphate: an old problem with new
      solutions?

PMID- 25378588
TI  - Severe vascular calcification and tumoral calcinosis in a family with
      hyperphosphatemia: a fibroblast growth factor 23 mutation identified by exome
      sequencing.
AB  - BACKGROUND: Tumoral calcinosis is an autosomal recessive disorder characterized
      by ectopic calcification and hyperphosphatemia. METHODS: We describe a family
      with tumoral calcinosis requiring amputations. The predominant metabolic anomaly
      identified in three affected family members was hyperphosphatemia. Biochemical
      and phenotypic analysis of 13 kindred members, together with exome analysis of 6
      members, was performed. RESULTS: We identified a novel Q67K mutation in
      fibroblast growth factor 23 (FGF23), segregating with a null (deletion) allele on
      the other FGF23 homologue in three affected members. Affected siblings had high
      circulating plasma C-terminal FGF23 levels, but undetectable intact FGF23 or N
      terminal FGF23, leading to loss of FGF23 function. CONCLUSIONS: This suggests
      that in human, as in experimental models, severe prolonged hyperphosphatemia may
      be sufficient to produce bone differentiation proteins in vascular cells, and
      vascular calcification severe enough to require amputation. Genetic modifiers may
      contribute to the phenotypic variation within and between families.

PMID- 25378590
TI  - Allotransplantation using a diseased kidney: when a swallow makes a summer.

PMID- 25378591
TI  - Intestinal expression of Fas and Fas ligand is upregulated by bacterial signaling
      through TLR4 and TLR5, with activation of Fas modulating intestinal TLR-mediated
      inflammation.
AB  - TLRs play an important role in mediating intestinal inflammation and homeostasis.
      Fas is best studied in terms of its function in apoptosis, but recent studies
      demonstrate that Fas signaling may mediate additional functions such as
      inflammation. The role of Fas, and the Fas ligand (FasL), in the intestine is
      poorly understood. The aim of this study was to evaluate potential cross-talk
      between TLRs and Fas/FasL system in intestinal epithelial cells (IECs). IECs were
      stimulated with TLR ligands, and expression of Fas and FasL was investigated.
      Treatment with TLR4 and TLR5 ligands, but not TLR2 and 9 ligands, increased
      expression of Fas and FasL in IECs in vitro. Consistent with this finding,
      expression of intestinal Fas and FasL was reduced in vivo in the epithelium of
      TLR4 knockout (KO), 5KO, and germ-free mice, but not in TLR2KO mice. Modulating
      Fas signaling using agonistic anti-Fas augmented TLR4- and TLR5-mediated TNF
      alpha and IL-8 production by IECs. In addition, suppression of Fas in IECs
      reduced the ability of TLR4 and TLR5 ligands and the intestinal pathogens
      Salmonella typhimurium and Listeria monocytogenes to induce the expression of IL
      8. In conclusion, this study demonstrates that extensive cross-talk in IECs
      occurs between the Fas and TLR signaling pathways, with the FasL/Fas system
      playing a role in TLR-mediated inflammatory responses in the intestine. 

PMID- 25378592
TI  - Diet-induced obesity does not impact the generation and maintenance of primary
      memory CD8 T cells.
AB  - The extent to which obesity compromises the differentiation and maintenance of
      protective memory CD8 T cell responses and renders obese individuals susceptible
      to infection remains unknown. In this study, we show that diet-induced obesity
      did not impact the maintenance of pre-existing memory CD8 T cells, including
      acquisition of a long-term memory phenotype (i.e., CD27(hi), CD62L(hi),
      KLRG1(lo)) and function (i.e., cytokine production, secondary expansion, and
      memory CD8 T cell-mediated protection). Additionally, obesity did not influence
      the differentiation and maintenance of newly evoked memory CD8 T cell responses
      in inbred and outbred hosts generated in response to different types of systemic
      (LCMV, L. monocytogenes) and/or localized (influenza virus) infections.
      Interestingly, the rate of naive-to-memory CD8 T cell differentiation after a
      peptide-coated dendritic cell immunization was similar in lean and obese hosts,
      suggesting that obesity-associated inflammation, unlike pathogen- or adjuvant
      induced inflammation, did not influence the development of endogenous memory CD8
      T cell responses. Therefore, our studies reveal that the obese environment does
      not influence the development or maintenance of memory CD8 T cell responses that
      are either primed before or after obesity is established, a surprising notion
      with important implications for future studies aiming to elucidate the role
      obesity plays in host susceptibility to infections. 

PMID- 25378593
TI  - Cutting edge: Genetic variation in TLR1 is associated with Pam3CSK4-induced
      effector T cell resistance to regulatory T cell suppression.
AB  - TLR play essential roles in the initiation and modulation of immune responses.
      TLR1/TLR2 heterodimers recognize triacylated bacterial lipopeptides, including
      the synthetic TLR1/2 lipopeptide Pam3CSK4. Genetic variation in TLR1 is
      associated with outcomes in diseases in which regulatory T cells (Treg) play a
      role, including asthma and allergy. To determine whether genetic polymorphisms in
      TLR1 are associated with alterations in Treg suppression of effector T cells
      (Teff), we performed in vitro suppression assays in healthy individuals with
      various haplotypes in TLR1. We show that functional genetic polymorphisms in TLR1
      modify surface expression of TLR1 on T lymphocytes and confer enhanced Teff
      resistance to Treg suppression in the presence of Pam3CSK4. These effects are
      mediated, in part, by IL-6 and inhibited by blocking IL-6 signaling through
      STAT3. These findings suggest that TLR1 polymorphisms could influence immune
      related disease through Teff resistance to Treg suppression. 

PMID- 25378598
TI  - Conservation. Plan to protect Great Barrier Reef under fire.

PMID- 25378594
TI  - Rictor negatively regulates high-affinity receptors for IgE-induced mast cell
      degranulation.
AB  - Rictor is a regulatory component of the mammalian target of rapamycin (mTOR)
      complex 2 (mTORC2). We have previously demonstrated that rictor expression is
      substantially downregulated in terminally differentiated mast cells as compared
      with their immature or transformed counterparts. However, it is not known whether
      rictor and mTORC2 regulate mast cell activation. In this article, we show that
      mast cell degranulation induced by aggregation of high-affinity receptors for IgE
      (FcepsilonRI) is negatively regulated by rictor independently of mTOR. We found
      that inhibition of mTORC2 by the dual mTORC1/mTORC2 inhibitor Torin1 or by
      downregulation of mTOR by short hairpin RNA had no impact on FcepsilonRI-induced
      degranulation, whereas downregulation of rictor itself resulted in an increased
      sensitivity (~50-fold) of cells to FcepsilonRI aggregation with enhancement of
      degranulation. This was linked to a similar enhancement in calcium mobilization
      and cytoskeletal rearrangement attributable to increased phosphorylation of LAT
      and PLCgamma1. In contrast, degranulation and calcium responses elicited by the G
      protein-coupled receptor ligand, C3a, or by thapsigargin, which induces a
      receptor-independent calcium signal, was unaffected by rictor knockdown.
      Overexpression of rictor, in contrast with knockdown, suppressed FcepsilonRI
      mediated degranulation. Taken together, these data provide evidence that rictor
      is a multifunctional signaling regulator that can regulate FcepsilonRI-mediated
      degranulation independently of mTORC2. 

PMID- 25378595
TI  - CD4 T cells specific for a latency-associated gamma-herpesvirus epitope are
      polyfunctional and cytotoxic.
AB  - The oncogenic gamma-herpesviruses EBV and Kaposi sarcoma-associated herpesvirus
      are ubiquitous human pathogens that establish lifelong latent infections
      maintained by intermittent viral reactivation and reinfection. Effector CD4 T
      cells are critical for control of viral latency and in immune therapies for virus
      associated tumors. In this study, we exploited gammaHV68 infection of mice to
      enhance our understanding of the CD4 T cell response during gamma-herpesvirus
      infection. Using a consensus prediction approach, we identified 16 new CD4
      epitope-specific responses that arise during lytic infection. An additional
      epitope encoded by the M2 protein induced uniquely latency-associated CD4 T
      cells, which were not detected at the peak of lytic infection but only during
      latency and were not induced postinfection with a latency-deficient virus. M2
      specific CD4 T cells were selectively cytotoxic, produced multiple antiviral
      cytokines, and sustained IL-2 production. Identification of latency-associated
      cytolytic CD4 T cells will aid in dissecting mechanisms of CD4 immune control of
      gamma-herpesvirus latency and the development of therapeutic approaches to
      control viral reactivation and pathology. 

PMID- 25378599
TI  - Infectious Diseases. Delays hinder Ebola genomics.

PMID- 25378600
TI  - Ecology. What's killing the reindeer?

PMID- 25378596
TI  - Borrelia burgdorferi arthritis-associated locus Bbaa1 regulates Lyme arthritis
      and K/B*N serum transfer arthritis through intrinsic control of type I IFN
      production.
AB  - Localized upregulation of type I IFN was previously implicated in development of
      Borrelia burgdorferi-induced arthritis in C3H mice, and was remarkable due to its
      absence in the mildly arthritic C57BL/6 (B6) mice. Independently, forward
      genetics analysis identified a quantitative trait locus on Chr4, termed B.
      burgdorferi-associated locus 1 (Bbaa1), that regulates Lyme arthritis severity
      and includes the 15 type I IFN genes. Involvement of Bbaa1 in arthritis
      development was confirmed in B6 mice congenic for the C3H allele of Bbaa1 (B6.C3
      Bbaa1), which developed more severe Lyme arthritis and K/B*N model of rheumatoid
      arthritis (RA) than did parental B6 mice. Administration of a type I IFN receptor
      blocking mAb reduced the severity of both Lyme arthritis and RA in B6.C3-Bbaa1
      mice, formally linking genetic elements within Bbaa1 to pathological production
      of type I IFN. Bone marrow-derived macrophages from Bbaa1 congenic mice
      implicated this locus as a regulator of type I IFN induction and downstream
      target gene expression. Bbaa1-mediated regulation of IFN-inducible genes was
      upstream of IFN receptor-dependent amplification; however, the overall magnitude
      of the response was dependent on autocrine/paracrine responses to IFN-beta. In
      addition, the Bbaa1 locus modulated the functional phenotype ascribed to bone
      marrow-derived macrophages: the B6 allele promoted expression of M2 markers,
      whereas the C3H allele promoted induction of M1 responses. This report identifies
      a genetic locus physically and functionally linked to type I IFN that contributes
      to the pathogenesis of both Lyme and RA. 

PMID- 25378601
TI  - Social Science. An Internet research project draws conservative ire.

PMID- 25378603
TI  - A glimpse of cosmic dawn.

PMID- 25378602
TI  - Microbiology. Genetics may foster bugs that keep you thin.

PMID- 25378604
TI  - Rare earth.

PMID- 25378605
TI  - Astronomy. The other half of the universe?

PMID- 25378606
TI  - Evolution. Searching for new branches on the tree of life.

PMID- 25378607
TI  - Virology. Leaping the norovirus hurdle.

PMID- 25378608
TI  - Cell Biology. Local synthesis and disposal.

PMID- 25378609
TI  - Earth Science. Coping with low ocean sulfate.

PMID- 25378610
TI  - Melting Mechanisms. Simulations provide a rare look at real melting.

PMID- 25378611
TI  - Environment and Development. Brazil's environmental leadership at risk.

PMID- 25378612
TI  - Hidden effects of mouse chow.

PMID- 25378613
TI  - Earthshaking energy development plans.

PMID- 25378615
TI  - Give young scientists a level playing field.

PMID- 25378617
TI  - Coherent transmutation of electrons into fractionalized anyons.
AB  - Electrons have three quantized properties-charge, spin, and Fermi statistics-that
      are directly responsible for a vast array of phenomena. Here we show how these
      properties can be coherently and dynamically stripped from the electron as it
      enters a certain exotic state of matter known as a quantum spin liquid (QSL). In
      a QSL, electron spins collectively form a highly entangled quantum state that
      gives rise to the fractionalization of spin, charge, and statistics. We show that
      certain QSLs host distinct, topologically robust boundary types, some of which
      allow the electron to coherently enter the QSL as a fractionalized quasi
      particle, leaving its spin, charge, or statistics behind. We use these ideas to
      propose a number of universal, conclusive experimental signatures that would
      establish fractionalization in QSLs. 

PMID- 25378618
TI  - Reduction of aryl halides by consecutive visible light-induced electron transfer
      processes.
AB  - Biological photosynthesis uses the energy of several visible light photons for
      the challenging oxidation of water, whereas chemical photocatalysis typically
      involves only single-photon excitation. Perylene bisimide is reduced by visible
      light photoinduced electron transfer (PET) to its stable and colored radical
      anion. We report here that subsequent excitation of the radical anion accumulates
      sufficient energy for the reduction of stable aryl chlorides giving aryl
      radicals, which were trapped by hydrogen atom donors or used in carbon-carbon
      bond formation. This consecutive PET (conPET) overcomes the current energetic
      limitation of visible light photoredox catalysis and allows the photocatalytic
      conversion of less reactive chemical bonds in organic synthesis. 

PMID- 25378619
TI  - Microscopic mechanisms of equilibrium melting of a solid.
AB  - The melting of a solid, like other first-order phase transitions, exhibits an
      intrinsic time-scale disparity: The time spent by the system in metastable states
      is orders of magnitude longer than the transition times between the states. Using
      rare-event sampling techniques, we find that melting of representative solids
      here, copper and aluminum-occurs via multiple, competing pathways involving the
      formation and migration of point defects or dislocations. Each path is
      characterized by multiple barrier-crossing events arising from multiple
      metastable states within the solid basin. At temperatures approaching
      superheating, melting becomes a single barrier-crossing process, and at the limit
      of superheating, the melting mechanism is driven by a vibrational instability.
      Our findings reveal the importance of nonlocal behavior, suggesting a revision of
      the perspective of classical nucleation theory. 

PMID- 25378620
TI  - On the origin of near-infrared extragalactic background light anisotropy.
AB  - Extragalactic background light (EBL) anisotropy traces variations in the total
      production of photons over cosmic history and may contain faint, extended
      components missed in galaxy point-source surveys. Infrared EBL fluctuations have
      been attributed to primordial galaxies and black holes at the epoch of
      reionization (EOR) or, alternately, intrahalo light (IHL) from stars tidally
      stripped from their parent galaxies at low redshift. We report new EBL anisotropy
      measurements from a specialized sounding rocket experiment at 1.1 and 1.6
      micrometers. The observed fluctuations exceed the amplitude from known galaxy
      populations, are inconsistent with EOR galaxies and black holes, and are largely
      explained by IHL emission. The measured fluctuations are associated with an EBL
      intensity that is comparable to the background from known galaxies measured
      through number counts and therefore a substantial contribution to the energy
      contained in photons in the cosmos. 

PMID- 25378621
TI  - Sulfate was a trace constituent of Archean seawater.
AB  - In the low-oxygen Archean world (>2400 million years ago), seawater sulfate
      concentrations were much lower than today, yet open questions frustrate the
      translation of modern measurements of sulfur isotope fractionations into
      estimates of Archean seawater sulfate concentrations. In the water column of Lake
      Matano, Indonesia, a low-sulfate analog for the Archean ocean, we find large (>20
      per mil) sulfur isotope fractionations between sulfate and sulfide, but the
      underlying sediment sulfides preserve a muted range of delta(34)S values. Using
      models informed by sulfur cycling in Lake Matano, we infer Archean seawater
      sulfate concentrations of less than 2.5 micromolar. At these low concentrations,
      marine sulfate residence times were likely 10(3) to 10(4) years, and sulfate
      scarcity would have shaped early global biogeochemical cycles, possibly
      restricting biological productivity in Archean oceans. 

PMID- 25378622
TI  - Neoarchean carbonate-associated sulfate records positive Delta33S anomalies.
AB  - Mass-independent fractionation of sulfur isotopes (reported as Delta(33)S)
      recorded in Archean sedimentary rocks helps to constrain the composition of
      Earth's early atmosphere and the timing of the rise of oxygen ~2.4 billion years
      ago. Although current hypotheses predict uniformly negative Delta(33)S for
      Archean seawater sulfate, this remains untested through the vast majority of
      Archean time. We applied x-ray absorption spectroscopy to investigate the low
      sulfate content of particularly well-preserved Neoarchean carbonates and mass
      spectrometry to measure their Delta(33)S signatures. We report unexpected, large,
      widespread positive Delta(33)S values from stratigraphic sections capturing over
      70 million years and diverse depositional environments. Combined with the pyrite
      record, these results show that sulfate does not carry the expected negative
      Delta(33)S from sulfur mass-independent fractionation in the Neoarchean
      atmosphere. 

PMID- 25378623
TI  - Large sulfur isotope fractionations associated with Neoarchean microbial sulfate
      reduction.
AB  - The minor extent of sulfur isotope fractionation preserved in many Neoarchean
      sedimentary successions suggests that sulfate-reducing microorganisms played an
      insignificant role in ancient marine environments, despite evidence that these
      organisms evolved much earlier. We present bulk, microdrilled, and ion probe
      sulfur isotope data from carbonate-associated pyrite in the ~2.5-billion-year-old
      Batatal Formation of Brazil, revealing large mass-dependent fractionations
      (approaching 50 per mil) associated with microbial sulfate reduction, as well as
      consistently negative Delta(33)S values (~ -2 per mil) indicative of atmospheric
      photochemical reactions. Persistent (33)S depletion through ~60 meters of shallow
      marine carbonate implies long-term stability of seawater sulfate abundance and
      isotope composition. In contrast, a negative Delta(33)S excursion in lower
      Batatal strata indicates a response time of ~40,000 to 150,000 years, suggesting
      Neoarchean sulfate concentrations between ~1 and 10 MUM. 

PMID- 25378624
TI  - Bats jamming bats: food competition through sonar interference.
AB  - Communication signals are susceptible to interference ("jamming") from
      conspecifics and other sources. Many active sensing animals, including bats and
      electric fish, alter the frequency of their emissions to avoid inadvertent
      jamming from conspecifics. We demonstrated that echolocating bats adaptively jam
      conspecifics during competitions for food. Three-dimensional flight path
      reconstructions and audio-video field recordings of foraging bats (Tadarida
      brasiliensis) revealed extended interactions in which bats emitted sinusoidal
      frequency-modulated ultrasonic signals that interfered with the echolocation of
      conspecifics attacking insect prey. Playbacks of the jamming call, but not of
      control sounds, caused bats to miss insect targets. This study demonstrates
      intraspecific food competition through active disruption of a competitor's
      sensing during food acquisition. 

PMID- 25378625
TI  - Targeting and plasticity of mitochondrial proteins revealed by proximity-specific
      ribosome profiling.
AB  - Nearly all mitochondrial proteins are nuclear-encoded and are targeted to their
      mitochondrial destination from the cytosol. Here, we used proximity-specific
      ribosome profiling to comprehensively measure translation at the mitochondrial
      surface in yeast. Most inner-membrane proteins were cotranslationally targeted to
      mitochondria, reminiscent of proteins entering the endoplasmic reticulum (ER).
      Comparison between mitochondrial and ER localization demonstrated that the vast
      majority of proteins were targeted to a specific organelle. A prominent exception
      was the fumarate reductase Osm1, known to reside in mitochondria. We identified a
      conserved ER isoform of Osm1, which contributes to the oxidative protein-folding
      capacity of the organelle. This dual localization was enabled by alternative
      translation initiation sites encoding distinct targeting signals. These findings
      highlight the exquisite in vivo specificity of organellar targeting mechanisms. 

PMID- 25378626
TI  - Enteric bacteria promote human and mouse norovirus infection of B cells.
AB  - The cell tropism of human noroviruses and the development of an in vitro
      infection model remain elusive. Although susceptibility to individual human
      norovirus strains correlates with an individual's histo-blood group antigen
      (HBGA) profile, the biological basis of this restriction is unknown. We
      demonstrate that human and mouse noroviruses infected B cells in vitro and likely
      in vivo. Human norovirus infection of B cells required the presence of HBGA
      expressing enteric bacteria. Furthermore, mouse norovirus replication was reduced
      in vivo when the intestinal microbiota was depleted by means of oral antibiotic
      administration. Thus, we have identified B cells as a cellular target of
      noroviruses and enteric bacteria as a stimulatory factor for norovirus infection,
      leading to the development of an in vitro infection model for human noroviruses. 

PMID- 25378628
TI  - Reflections of a woman pioneer.

PMID- 25378629
TI  - Economics in the age of big data.
AB  - The quality and quantity of data on economic activity are expanding rapidly.
      Empirical research increasingly relies on newly available large-scale
      administrative data or private sector data that often is obtained through
      collaboration with private firms. Here we highlight some challenges in accessing
      and using these new data. We also discuss how new data sets may change the
      statistical methods used by economists and the types of questions posed in
      empirical research. 

PMID- 25378627
TI  - Phylogenomics resolves the timing and pattern of insect evolution.
AB  - Insects are the most speciose group of animals, but the phylogenetic
      relationships of many major lineages remain unresolved. We inferred the phylogeny
      of insects from 1478 protein-coding genes. Phylogenomic analyses of nucleotide
      and amino acid sequences, with site-specific nucleotide or domain-specific amino
      acid substitution models, produced statistically robust and congruent results
      resolving previously controversial phylogenetic relations hips. We dated the
      origin of insects to the Early Ordovician [~479 million years ago (Ma)], of
      insect flight to the Early Devonian (~406 Ma), of major extant lineages to the
      Mississippian (~345 Ma), and the major diversification of holometabolous insects
      to the Early Cretaceous. Our phylogenomic study provides a comprehensive reliable
      scaffold for future comparative analyses of evolutionary innovations among
      insects.

PMID- 25378630
TI  - Principles of ER cotranslational translocation revealed by proximity-specific
      ribosome profiling.
AB  - Localized protein synthesis is a fundamental mechanism for creating distinct
      subcellular environments. Here we developed a generalizable proximity-specific
      ribosome profiling strategy that enables global analysis of translation in
      defined subcellular locations. We applied this approach to the endoplasmic
      reticulum (ER) in yeast and mammals. We observed the large majority of secretory
      proteins to be cotranslationally translocated, including substrates capable of
      posttranslational insertion in vitro. Distinct translocon complexes engaged
      nascent chains at different points during synthesis. Whereas most proteins
      engaged the ER immediately after or even before signal sequence (SS) emergence, a
      class of Sec66-dependent proteins entered with a looped SS conformation. Finally,
      we observed rapid ribosome exchange into the cytosol after translation
      termination. These data provide insights into how distinct translocation
      mechanisms act in concert to promote efficient cotranslational recruitment. 

PMID- 25378633
TI  - Light at the end of the tunnel: towards an effective drug therapy for surgery-
      and radiation-refractory meningioma.

PMID- 25378632
TI  - Thrombin-processed Ecrg4 recruits myeloid cells and induces antitumorigenic
      inflammation.
AB  - BACKGROUND: Extensive infiltration of brain tumors by microglia and macrophages
      is a hallmark of tumor progression, and yet the overall tumor microenvironment is
      characterized by an immunosuppressive phenotype. Here we identify esophageal
      cancer-related gene 4 (Ecrg4) as a novel thrombin-processed monocyte
      chemoattractant that recruits myeloid cells, promotes their activation, and leads
      to a blockade of tumor progression. METHODS: Both xenograft glioma and syngeneic
      glioma models were used to measure orthotopic tumor progression and overall
      survival. Flow cytometry and immunohistochemical analyses were performed to
      assess myeloid cell localization, recruitment, and activation. RESULTS: Ecrg4
      promotes monocyte recruitment and activation of microglia in a T-/B-cell
      independent mechanism, which leads to a reduction in glioma tumor burden and
      increased survival. Mutational analysis reveals that the biological activity of
      Ecrg4 is dependent on a thrombin-processing site at the C-terminus, inducing
      monocyte invasion in vivo and in vitro. Furthermore, tumor-induced myeloid cell
      recruitment is impaired in Ecrg4 knockout mice, leading to increased tumor burden
      and decreased survival. CONCLUSIONS: Together, these results identify Ecrg4 as a
      paracrine factor that activates microglia and is chemotactic for monocytes, with
      potential as an antitumor therapeutic.

PMID- 25378634
TI  - Disulfiram modulates stemness and metabolism of brain tumor initiating cells in
      atypical teratoid/rhabdoid tumors.
AB  - BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RT) are among the most
      malignant pediatric brain tumors. Cells from brain tumors with high aldehyde
      dehydrogenase (ALDH) activity have a number of characteristics that are similar
      to brain tumor initiating cells (BTICs). This study aimed to evaluate the
      therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs
      from AT/RT. METHODS: Primary cultured BTICs from AT/RT were stained with
      Aldefluor and isolated by fluorescence activated cell sorting. The therapeutic
      effect of DSF against BTICs from AT/RT was confirmed in vitro and in vivo.
      RESULTS: AT/RT cells displayed a high expression of ALDH. DSF demonstrated a more
      potent cytotoxic effect on ALDH(+) AT/RT cells compared with standard anticancer
      agents. Notably, treatment with DSF did not have a considerable effect on normal
      neural stem cells or fibroblasts. DSF significantly inhibited the ALDH enzyme
      activity of AT/RT cells. DSF decreased self-renewal ability, cell viability, and
      proliferation potential and induced apoptosis and cell cycle arrest in ALDH(+)
      AT/RT cells. Importantly, DSF reduced the metabolism of ALDH(+) AT/RT cells by
      increasing the nicotinamide adenine dinucleotide ratio of NAD(+)/NADH and
      regulating Silent mating type Information Regulator 2 homolog 1 (SIRT1), nuclear
      factor-kappaB, Lin28A/B, and miRNA let-7g. Animals in the DSF-treated group
      demonstrated a reduction of tumor volume (P < .05) and a significant survival
      benefit (P = .02). CONCLUSION: Our study demonstrated the therapeutic potential
      of DSF against BTICs from AT/RT and suggested the possibility of ALDH inhibition
      for clinical application.

PMID- 25378635
TI  - Host fate is rapidly determined by innate effector-microbial interactions during
      Acinetobacter baumannii bacteremia.
AB  - BACKGROUND: Acinetobacter baumannii is one of the most antibiotic-resistant
      pathogens. Defining mechanisms driving pathogenesis is critical to enable new
      therapeutic approaches. METHODS: We studied virulence differences across a
      diverse panel of A. baumannii clinical isolates during murine bacteremia to
      elucidate host-microbe interactions that drive outcome. RESULTS: We identified
      hypervirulent strains that were lethal at low intravenous inocula and achieved
      very high early, and persistent, blood bacterial densities. Virulent strains were
      nonlethal at low inocula but lethal at 2.5-fold higher inocula. Finally,
      relatively avirulent (hypovirulent) strains were nonlethal at 20-fold higher
      inocula and were efficiently cleared by early time points. In vivo virulence
      correlated with in vitro resistance to complement and macrophage uptake.
      Depletion of complement, macrophages, and neutrophils each independently
      increased bacterial density of the hypovirulent strain but insufficiently to
      change lethality. However, disruption of all 3 effector mechanisms enabled early
      bacterial densities similar to hypervirulent strains, rendering infection 100%
      fatal. CONCLUSIONS: The lethality of A. baumannii strains depends on distinct
      stages. Strains resistant to early innate effectors are able to establish very
      high early bacterial blood density, and subsequent sustained bacteremia leads to
      Toll-like receptor 4-mediated hyperinflammation and lethality. These results have
      important implications for translational efforts to develop therapies that
      modulate host-microbe interactions.

PMID- 25378636
TI  - HIV Nef promotes expression of B-lymphocyte stimulator by blood dendritic cells
      during HIV infection in humans.
AB  - Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly
      through production of growth factors such as B lymphocyte stimulator (BLyS; also
      known as "B-cell factor belonging to the tumor necrosis factor family" [BAFF]).
      We have recently shown that, in human immunodeficiency virus (HIV)-infected
      individuals with rapid and those with classic disease progression, B-cell
      dysregulations were associated with increased BLyS expression in plasma and by
      blood myeloid DCs (mDCs), in contrast to aviremic HIV-infected individuals with
      slow disease progression (also known as "elite controllers"). In previous work
      with transgenic mice expressing HIV genes, B-cell dysregulations were concomitant
      with altered mDCs and dependent on HIV negative factor (Nef). We now report that
      HIV Nef is detected early after infection and despite successful therapy in
      plasma and BLyS-overexpressing blood mDCs of HIV-infected rapid and classic
      progressors, whereas it is low to undetectable in aviremic slow progressors. In
      vitro, HIV Nef drives monocyte-derived DCs toward BLyS overexpression through a
      process involving STAT1. Importantly, this is counteracted in the presence of all
      trans retinoic acid. Nef thus contributes to high BLyS proinflammatory profiles
      in HIV-infected individuals. 

PMID- 25378637
TI  - Effect of influenza A(H5N1) vaccine prepandemic priming on CD4+ T-cell responses.
AB  - INTRODUCTION: Previous priming with avian influenza vaccines results in more
      rapid and more robust neutralizing antibody responses upon revaccination, but the
      role CD4(+) T cells play in this process is not currently known. METHODS: Human
      subjects previously enrolled in trials of inactivated influenza A(H5N1) vaccines
      and naive subjects were immunized with an inactivated subunit influenza
      A/Indonesia/5/05(H5N1) vaccine. Neutralizing antibody responses were measured by
      a microneutralization assay, and hemagglutinin (HA)-specific and nucleoprotein
      (NP)-specific CD4(+) T-cell responses were quantified using interferon gamma
      enzyme-linked immunosorbent spot assays. RESULTS: While vaccination induced
      barely detectable CD4(+) T-cell responses specific for HA in the previously
      unprimed group, primed subjects had readily detectable HA-specific memory CD4(+)
      T cells at baseline and mounted a more robust response to HA-specific epitopes
      after vaccination. There were no differences between groups when conserved NP
      specific CD4(+) T-cell responses were examined. Interestingly, neutralizing
      antibody responses following revaccination were significantly higher in
      individuals who mounted a CD4(+) T-cell response to the H5 HA protein, a
      correlation not observed for NP-specific responses. CONCLUSIONS: These findings
      suggest that prepandemic vaccination results in an enriched population of HA
      specific CD4(+) T cells that are recruited on rechallenge with a drifted vaccine
      variant and contribute to more robust and more rapid neutralizing antibody
      responses.

PMID- 25378638
TI  - The Lazarus Funnel: a blinded prospective randomized in vitro trial of a novel CE
      marked thrombectomy assist device.
AB  - INTRODUCTION: The use of retrievable stents for acute ischemic stroke (AIS) may
      result in the release of distal emboli in 12-22% of cases. The Lazarus Funnel is
      a novel CE-marked thrombectomy assist device designed to capture the stentriever
      and thrombus to minimize the likelihood of distal embolization. To study this
      technology, we performed a randomized blinded in vitro evaluation of this device.
      METHODS: A cerebral flow model was used as an in vitro simulator for cerebral
      arterial thrombectomy procedures. Stratified block randomization was performed
      following embolus injection into one of three cohorts: Solitaire stentriever plus
      guide catheter (control); control plus proximal Funnel placement; or control plus
      distal Funnel placement. Time to embolectomy, recanalization, and incidence of
      distal emboli were determined by a blinded observer. RESULTS: Forty-five
      thrombectomy trials were performed (15 in each group). The average time required
      for thrombectomy in each group was 8 min 26 s, 11 min 0 s and 9 min 24 s,
      respectively (p=NS). Use of the Funnel was associated with significantly improved
      recanalization compared with stentriever alone (p<0.01). Use of the proximal
      Funnel resulted in a 25% increase in successful recanalization and a 20%
      reduction in distal emboli. Use of the distal Funnel resulted in a 200% increase
      in successful recanalization and a 60% reduction in emboli. CONCLUSIONS: In this
      AIS embolism flow model with Solitaire thrombectomy, the Lazarus Funnel resulted
      in a significant increase in recanalization and significant reduction in distal
      emboli without increase in time to recanalization.

PMID- 25378640
TI  - Endovascular management of intracranial blister aneurysms: spectrum and
      limitations of contemporary techniques.
AB  - BACKGROUND: Intracranial blister aneurysms are rare lesions that are notoriously
      more difficult to treat than typical saccular aneurysms. High complication rates
      associated with surgery have sparked considerable interest in endovascular
      techniques, though not well-studied, to treat blister aneurysms. OBJECTIVE: To
      evaluate our experience using various endovascular approaches to treat blister
      aneurysms. METHODS: All consecutive blister aneurysms treated using an
      endovascular approach by the study authors over a 3-year period were
      retrospectively analyzed. A literature review was also performed. RESULTS: Nine
      patients with blister aneurysms underwent 11 endovascular interventions. In
      various combinations, stents were used in 8/11, coils in 5/11, and Onyx in 3/11
      procedures. At mean angiographic follow-up of 200 days, 8/9 aneurysms were
      completely occluded by endovascular means alone requiring no further treatment
      and 1/9 aneurysms required surgical bypass/trapping after one failed surgical and
      two failed endovascular treatments. At mean clinical follow-up of 416 days,
      modified Rankin Scale scores were improved in six patients, stable in two, and
      worsened in one patient. One complication occurred in 11 procedures (9%),
      resulting in a permanent neurologic deficit. No unintended endovascular parent
      vessel sacrifice, intraprocedural aneurysmal ruptures, antiplatelet-related
      complications, post-treatment aneurysmal re-ruptures, or deaths occurred.
      CONCLUSION: This series highlights both the spectrum and limitations of
      endovascular techniques currently used to treat blister aneurysms, including a
      novel application of stent-assisted Onyx embolization. Long-term follow-up and
      experience in larger studies are required to better define the role of
      endovascular therapy in the management of these difficult lesions.

PMID- 25378639
TI  - Collateral flow as causative of good outcomes in endovascular stroke therapy.
AB  - BACKGROUND: Endovascular reperfusion techniques are a promising intervention for
      acute ischemic stroke (AIS). Prior studies have identified markers of initial
      injury (arrival NIH stroke scale (NIHSS) or infarct volume) as predictive of
      outcome after these procedures. We sought to define the role of collateral flow
      at the time of presentation in determining the extent of initial ischemic injury
      and its influence on final outcome. METHODS: Demographic, clinical, laboratory,
      and radiographic data were prospectively collected on a consecutive cohort of
      patients who received endovascular therapy for acute cerebral ischemia at a
      single tertiary referral center from September 2004 to August 2010. RESULTS:
      Higher collateral grade as assessed by the American Society of Interventional and
      Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR)
      grading scheme on angiography at the time of presentation was associated with
      improved reperfusion rates after endovascular intervention, decreased post
      procedural hemorrhage, smaller infarcts on presentation and discharge, as well as
      improved neurological function on arrival to the hospital, discharge, and 90 days
      later. Patients matched by vessel occlusion, age, and time of onset demonstrated
      smaller strokes on presentation and better functional and radiographic outcome if
      found to have superior collateral flow. In multivariate analysis, lower
      collateral grade independently predicted higher NIHSS on arrival. CONCLUSIONS:
      Improved collateral flow in patients with AIS undergoing endovascular therapy was
      associated with improved radiographic and clinical outcomes. Independent of age,
      vessel occlusion and time, in patients with comparable ischemic burdens, changes
      in collateral grade alone led to significant differences in initial stroke
      severity as well as ultimate clinical outcome.

PMID- 25378642
TI  - Public biobanks: calculation and recovery of costs.
AB  - A calculation grid developed by an international expert group was tested across
      biobanks in six countries to evaluate costs for collections of various types of
      biospecimens. The assessment yielded a tool for setting specimen-access prices
      that were transparently related to biobank costs, and the tool was applied across
      three models of collaborative partnership. 

PMID- 25378643
TI  - Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and
      long-lasting CD4-dependent tumor immunity.
AB  - Translating the recent success of chimeric antigen receptor (CAR) T cell therapy
      for hematological malignancies to solid tumors will necessitate overcoming
      several obstacles, including inefficient T cell tumor infiltration and
      insufficient functional persistence. Taking advantage of an orthotopic model that
      faithfully mimics human pleural malignancy, we evaluated two routes of
      administration of mesothelin-targeted T cells using the M28z CAR. We found that
      intrapleurally administered CAR T cells vastly outperformed systemically infused
      T cells, requiring 30-fold fewer M28z T cells to induce long-term complete
      remissions. After intrapleural T cell administration, prompt in vivo antigen
      induced T cell activation allowed robust CAR T cell expansion and effector
      differentiation, resulting in enhanced antitumor efficacy and functional T cell
      persistence for 200 days. Regional T cell administration also promoted efficient
      elimination of extrathoracic tumor sites. This therapeutic efficacy was dependent
      on early CD4(+) T cell activation associated with a higher intratumoral CD4/CD8
      cell ratios and CD28-dependent CD4(+) T cell-mediated cytotoxicity. In contrast,
      intravenously delivered CAR T cells, even when accumulated at equivalent numbers
      in the pleural tumor, did not achieve comparable activation, tumor eradication,
      or persistence. The ability of intrapleurally administered T cells to circulate
      and persist supports the concept of delivering optimal CAR T cell therapy through
      "regional distribution centers." On the basis of these results, we are opening a
      phase 1 clinical trial to evaluate the safety of intrapleural administration of
      mesothelin-targeted CAR T cells in patients with primary or secondary pleural
      malignancies. 

PMID- 25378644
TI  - Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome
      drug resistance to the microtubule inhibitor eribulin.
AB  - Eribulin mesylate was developed as a potent microtubule-targeting cytotoxic agent
      to treat taxane-resistant cancers, but recent clinical trials have shown that it
      eventually fails in many patient subpopulations for unclear reasons. To
      investigate its resistance mechanisms, we developed a fluorescent analog of
      eribulin with pharmacokinetic (PK) properties and cytotoxic activity across a
      human cell line panel that are sufficiently similar to the parent drug to study
      its cellular PK and tissue distribution. Using intravital imaging and automated
      tracking of cellular dynamics, we found that resistance to eribulin and the
      fluorescent analog depended directly on the multidrug resistance protein 1
      (MDR1). Intravital imaging allowed for real-time analysis of in vivo PK in tumors
      that were engineered to be spatially heterogeneous for taxane resistance, whereby
      an MDR1-mApple fusion protein distinguished resistant cells fluorescently. In
      vivo, MDR1-mediated drug efflux and the three-dimensional tumor vascular
      architecture were discovered to be critical determinants of drug accumulation in
      tumor cells. We furthermore show that standard intravenous administration of a
      third-generation MDR1 inhibitor, HM30181, failed to rescue drug accumulation;
      however, the same MDR1 inhibitor encapsulated within a nanoparticle delivery
      system reversed the multidrug-resistant phenotype and potentiated the eribulin
      effect in vitro and in vivo in mice. Our work demonstrates that in vivo
      assessment of cellular PK of an anticancer drug is a powerful strategy for
      elucidating mechanisms of drug resistance in heterogeneous tumors and evaluating
      strategies to overcome this resistance. 

PMID- 25378646
TI  - Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman
      primates.
AB  - Using therapeutic antibodies that need to cross the blood-brain barrier (BBB) to
      treat neurological disease is a difficult challenge. We have shown that
      bispecific antibodies with optimized binding to the transferrin receptor (TfR)
      that target beta-secretase (BACE1) can cross the BBB and reduce brain amyloid
      beta (Abeta) in mice. Can TfR enhance antibody uptake in the primate brain? We
      describe two humanized TfR/BACE1 bispecific antibody variants. Using a human TfR
      knock-in mouse, we observed that anti-TfR/BACE1 antibodies could cross the BBB
      and reduce brain Abeta in a TfR affinity-dependent fashion. Intravenous dosing of
      monkeys with anti-TfR/BACE1 antibodies also reduced Abeta both in cerebral spinal
      fluid and in brain tissue, and the degree of reduction correlated with the brain
      concentration of anti-TfR/BACE1 antibody. These results demonstrate that the TfR
      bispecific antibody platform can robustly and safely deliver therapeutic antibody
      across the BBB in the primate brain. 

PMID- 25378645
TI  - A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that
      primes, boosts, and sustains functional HCV-specific T cell memory.
AB  - A protective vaccine against hepatitis C virus (HCV) remains an unmet clinical
      need. HCV infects millions of people worldwide and is a leading cause of liver
      cirrhosis and hepatocellular cancer. Animal challenge experiments, immunogenetics
      studies, and assessment of host immunity during acute infection highlight the
      critical role that effective T cell immunity plays in viral control. In this
      first-in-man study, we have induced antiviral immunity with functional
      characteristics analogous to those associated with viral control in natural
      infection, and improved upon a vaccine based on adenoviral vectors alone. We
      assessed a heterologous prime-boost vaccination strategy based on a replicative
      defective simian adenoviral vector (ChAd3) and modified vaccinia Ankara (MVA)
      vector encoding the NS3, NS4, NS5A, and NS5B proteins of HCV genotype 1b.
      Analysis used single-cell mass cytometry and human leukocyte antigen class I
      peptide tetramer technology in healthy human volunteers. We show that HCV
      specific T cells induced by ChAd3 are optimally boosted with MVA, and generate
      very high levels of both CD8(+) and CD4(+) HCV-specific T cells targeting
      multiple HCV antigens. Sustained memory and effector T cell populations are
      generated, and T cell memory evolved over time with improvement of quality
      (proliferation and polyfunctionality) after heterologous MVA boost. We have
      developed an HCV vaccine strategy, with durable, broad, sustained, and balanced T
      cell responses, characteristic of those associated with viral control, paving the
      way for the first efficacy studies of a prophylactic HCV vaccine. 

PMID- 25378647
TI  - Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses
      determined from oral morphine rescue doses in the treatment of breakthrough
      cancer pain.
AB  - OBJECTIVE: A randomized, crossover, double-blinded placebo-controlled and non
      blinded active drug-controlled, comparative clinical trial was conducted to
      evaluate the efficacy and safety of sublingual fentanyl tablet. METHODS: Subjects
      were patients treated with strong opioids at fixed intervals for chronic cancer
      pain and with oral morphine as rescue medication for breakthrough pain.
      Sublingual fentanyl was administered at doses that were 1/25th (high dose) and
      1/50th (low dose) of the dose of rescue morphine and was compared with placebo
      and oral morphine. The primary endpoint was pain intensity difference at 30 min
      after administration. (Clinical Trials Government; NCT00684632). RESULTS: Fifty
      one patients were enrolled in the investigation. Their mean pain intensity in
      visual analog scale before rescue medication prior to the investigation was 60.96
      (16.44, standard deviation) mm. Compared with placebo, the low and high doses of
      sublingual fentanyl showed significant analgesic effects (least squares mean
      difference, 4.54 and 8.49 mm; P = 0.014, P < 0.001, respectively). Adverse
      reactions were observed in 17.6%, the most common being constipation, nausea and
      somnolence. The incidence of adverse reactions during the high-dose
      administration period was higher than that during the low-dose and active control
      drug administration periods. CONCLUSIONS: Patients treated with strong opioid
      analgesics at fixed intervals for chronic cancer pain and with oral morphine at
      doses up to 20 mg as rescue medication were investigated. The doses of sublingual
      fentanyl to treat breakthrough pain were determined from rescue morphine doses by
      use of conversion ratios. In these patients, administration of sublingual
      fentanyl at doses determined by a conversion ratio of 1/50 was effective and
      safe. Further studies are needed to validate the use of this conversion method.

PMID- 25378648
TI  - Randomized controlled trial comparing docetaxel-cisplatin combination with weekly
      docetaxel alone in elderly patients with advanced non-small-cell lung cancer:
      Japan Clinical Oncology Group (JCOG) 0207?.
AB  - OBJECTIVE: Prospective trials specifically designed for elderly patients with
      advanced non-small-cell lung cancer demonstrating the benefit of platinum-based
      therapies are still lacking. This trial was designed to clarify whether the
      addition of cisplatin to monotherapy could improve survival for elderly patients.
      METHODS: Elderly patients (age >=70 years, ECOG performance Status 0-1) with
      advanced non-small-cell lung cancer were randomized to receive docetaxel 20
      mg/m(2) plus cisplatin 25 mg/m(2) on Day 1, 8 and 15 (docetaxel plus cisplatin)
      or docetaxel 25 mg/m(2) on the same schedule (docetaxel). Both regimens were
      repeated every 4 weeks until disease progression. RESULTS: One hundred and twenty
      six patients were enrolled. Sixty-three were randomly assigned docetaxel plus
      cisplatin and 63 docetaxel monotherapy. Median age was 76 years (range 70-88).
      The second planned interim analysis was performed on 112 assessable patients
      (docetaxel/docetaxel plus cisplatin: 56/56). Although the formal criterion for
      stopping the trial was not met, the Data and Safety Monitoring Committee
      recommended study termination on ethical grounds based on the interaction (two
      sided P = 0.077, hazard ratios for <=74/>=75: 0.23/0.72) between age and subgroup
      and treatment arm, which suggested that docetaxel may not represent an adequate
      control arm regimen for the age subgroup of 70-74 years. CONCLUSIONS: The
      interpretation of study results is limited due to early stopping. Further study
      is needed to confirm survival benefit of platinum-based chemotherapy for elderly
      non-small-cell lung cancer [UMIN-CTR (www.umin.ac.jp/ctr/) ID: C000000146].

PMID- 25378649
TI  - Serum HER2 levels and HER2 status in tumor cells in advanced gastric cancer
      patients.
AB  - OBJECTIVE: Increased serum human epidermal growth factor receptor 2 levels have
      been found in metastatic breast cancer patients and are correlated with human
      epidermal growth factor receptor 2 overexpression in tumor cells. However, the
      prevalence of serum human epidermal growth factor receptor 2 in gastric cancer
      patients has not been elucidated. METHODS: We retrospectively analyzed formalin
      fixed paraffin-embedded tumor tissues and serum samples from 96 advanced gastric
      cancer patients. Human epidermal growth factor receptor 2 expression and gene
      amplification in tumor cells were determined by immunohistochemistry and
      fluorescence in situ hybridization. Serum human epidermal growth factor receptor
      2 levels were measured using a chemiluminescent immunoassay. Human epidermal
      growth factor receptor 2 positivity in tumor cells was defined as
      immunohistochemistry 2+ with fluorescence in situ hybridization positive or
      immunohistochemistry 3+ with any fluorescence in situ hybridization results.
      RESULTS: All tissue samples and serum samples were successfully measured.
      Nineteen patients (20%) were human epidermal growth factor receptor 2-positive in
      tumor cells. The median serum human epidermal growth factor receptor 2 level was
      9.3 ng/ml (range, 5.0-332.4 ng/ml), and serum human epidermal growth factor
      receptor 2 levels were significantly separated according to human epidermal
      growth factor receptor 2 status in tumor cells (P < 0.0001, Wilcoxon's rank sum
      test); median serum human epidermal growth factor receptor 2 levels in human
      epidermal growth factor receptor 2-negative patients and -positive patients were
      8.9 (range, 5.0-20.5) and 24.0 (range, 9.7-332.4), respectively. There were 15
      serum human epidermal growth factor receptor 2-positive patients (16%) using a
      cutoff value of 15 ng/ml. The sensitivity and the specificity of serum human
      epidermal growth factor receptor 2 with respect to human epidermal growth factor
      receptor 2 positivity in tumor cells were 53 and 94%, respectively. CONCLUSIONS:
      Serum human epidermal growth factor receptor 2 measurements cannot be substituted
      for tissue human epidermal growth factor receptor 2 diagnosis in advanced gastric
      cancer patients. However, serum human epidermal growth factor receptor 2 levels
      are associated with human epidermal growth factor receptor 2 overexpression in
      tumor cells. Further investigations of clinical significance of serum human
      epidermal growth factor receptor 2 as a predictive marker and a therapy
      monitoring marker are warranted.

PMID- 25378650
TI  - Effect of liver cirrhosis on metastasis in colorectal cancer patients: a
      nationwide population-based cohort study.
AB  - OBJECTIVE: The aim of this study is to evaluate the liver metastasis risk among
      colorectal cancer patients with liver cirrhosis. METHODS: This was a nationwide
      population-based cohort study of 2973 newly diagnosed colorectal cancer patients
      with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan
      between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio
      by the multivariate Cox proportional model and the incidence density were
      evaluated. RESULTS: The median time interval from the colorectal cancer diagnosis
      to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67
      months for non-liver cirrhosis group. The incidence density of liver metastasis
      was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non
      liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted
      hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk
      of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was
      27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with
      locoregional disease patients receiving surgery alone without adjuvant anti
      cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9
      vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs.
      16.6%, P = 0.009) both still had higher liver metastasis risk compared with their
      counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for
      hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus,
      other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%,
      respectively, (P = 0.03). CONCLUSIONS: Our study found that liver metastasis risk
      was underestimated and even higher in colorectal cancer patients with liver
      cirrhosis.

PMID- 25378651
TI  - Nidogen-1: a candidate biomarker for ovarian serous cancer.
AB  - OBJECTIVE: Effective biomarkers for early detection of ovarian cancer are needed.
      Our study previously showed that basement membrane protein, nidogen-1 plasma
      level was significantly increased in ovarian cancer patients. This study aimed to
      examine the plasma levels of nidogen-1 in a large patient population to evaluate
      its effectiveness in ovarian serous carcinoma and expression in tumor tissues.
      METHODS: The concentration of nidogen-1 in circulating plasma specimens of 265
      ovarian serous cancer patients and 98 healthy individuals were assayed by enzyme
      linked immunosorbent assay. The medical records of 265 ovarian serous cancer
      cases were reviewed retrospectively. The expression status of nidogen-1 in tumor
      tissues of 44 ovarian serous carcinoma patients was examined by
      immunohistochemical analysis. For statistical analysis, we used the Mann-Whitney
      U test, Fisher's exact test and receiver operating characteristic. RESULTS:
      Protein levels of nidogen-1 were considerably raised in the plasma from ovarian
      serous cancer patients compared with those in healthy controls (P < 0.001),
      especially elevated in patients with advanced stage and those received
      neoadjuvant chemotherapy followed by interval debulking surgery. However, it was
      irrelevant to the grade, chemotherapy sensitivity or residual tumor of the
      ovarian serous carcinoma cases investigated (P > 0.05). Receiver operating
      characteristic curve analysis for nidogen-1 showed that it could discriminate
      patients with ovarian serous carcinomas from healthy controls [areas under the
      curve (AUC): 0. 65, 95%CI, 0.59-0.71], but CA125 was superior (AUC: 0. 98, 95%CI,
      0.96-0.99). The immunohistochemical staining result showed that nidogen-1 protein
      was localized both in the cancer cell cytoplasm and intercellular substance,
      mainly expressed in extracellular matrix of ovarian serous carcinoma tissues (the
      positive rate was 77.3%). CONCLUSIONS: Our study suggests that plasma nidogen-1
      may be used as a diagnostic biomarker for ovarian serous carcinoma and can
      reflect the tumor burden.

PMID- 25378652
TI  - Proceedings: debilitating eye diseases.
AB  - Debilitating eye diseases such as age-related macular degeneration and retinitis
      pigmentosa currently represent a large unmet medical need that could potentially
      be addressed by stem cell therapy. A number of novel stem cell-based cellular
      therapies are now under development to treat a variety of eye diseases. The
      approaches being taken by the California Institute for Regenerative Medicine,
      together with its grantees, are discussed.

PMID- 25378653
TI  - Optimized cell survival and seeding efficiency for craniofacial tissue
      engineering using clinical stem cell therapy.
AB  - Traumatic injuries involving the face are very common, yet the clinical
      management of the resulting craniofacial deficiencies is challenging. These
      injuries are commonly associated with missing teeth, for which replacement is
      compromised due to inadequate jawbone support. Using cell therapy, we report the
      upper jaw reconstruction of a patient who lost teeth and 75% of the supporting
      jawbone following injury. A mixed population of bone marrow-derived autologous
      stem and progenitor cells was seeded onto beta-tricalcium phosphate (beta-TCP),
      which served as a scaffold to deliver cells directly to the defect. Conditions
      (temperature, incubation time) to achieve the highest cell survival and seeding
      efficiency were optimized. Four months after cell therapy, cone beam computed
      tomography and a bone biopsy were performed, and oral implants were placed to
      support an engineered dental prosthesis. Cell seeding efficiency (>81%) of the
      beta-TCP and survival during the seeding process (94%) were highest when cells
      were incubated with beta-TCP for 30 minutes, regardless of incubation
      temperature; however, at 1 hour, cell survival was highest when incubated at 4
      degrees C. Clinical, radiographic, and histological analyses confirmed that by 4
      months, the cell therapy regenerated 80% of the original jawbone deficiency with
      vascularized, mineralized bone sufficient to stably place oral implants.
      Functional and aesthetic rehabilitation of the patient was successfully completed
      with installation of a dental prosthesis 6 months following implant placement.
      This proof-of-concept clinical report used an evidence-based approach for the
      cell transplantation protocol used and is the first to describe a cell therapy
      for craniofacial trauma reconstruction. 

PMID- 25378654
TI  - Tissue-engineered vascular grafts created from human induced pluripotent stem
      cells.
AB  - The utility of human induced pluripotent stem cells (hiPSCs) to create tissue
      engineered vascular grafts was evaluated in this study. hiPSC lines were first
      induced into a mesenchymal lineage via a neural crest intermediate using a serum
      free, chemically defined differentiation scheme. Derived cells exhibited commonly
      known mesenchymal markers (CD90, CD105, and CD73 and negative marker CD45) and
      were shown to differentiate into several mesenchymal lineages (osteogenic,
      chondrogenic, and adipogenic). Functional vascular grafts were then engineered by
      culturing hiPSC-derived mesenchymal progenitor cells in a pulsatile bioreactor
      system over 8 weeks to induce smooth muscle cell differentiation and collagenous
      matrix generation. Histological analyses confirmed layers of calponin-positive
      smooth muscle cells in a collagen-rich matrix. Mechanical tests revealed that
      grafts had an average burst pressure of 700 mmHg, which is approximately half
      that of native veins. Additionally, studies revealed that karyotypically normal
      mesenchymal stem cell clones led to generation of grafts with predicted features
      of engineered vascular grafts, whereas derived clones having chromosomal
      abnormalities generated calcified vessel constructs, possibly because of cell
      apoptosis during culture. Overall, these results provide significant insight into
      the utility of hiPS cells for vascular graft generation. They pave the way for
      creating personalized, patient-specific vascular grafts for surgical
      applications, as well as for creating experimental models of vascular development
      and disease. 

PMID- 25378655
TI  - Concise review: umbilical cord blood transplantation: past, present, and future.
AB  - Allogeneic hematopoietic stem cell transplantation is an important treatment
      option for fit patients with poor-risk hematological malignancies; nevertheless,
      the lack of available fully matched donors limits the extent of its use.
      Umbilical cord blood has emerged as an effective alternate source of
      hematopoietic stem cell support. Transplantation with cord blood allows for
      faster availability of frozen sample and avoids invasive procedures for donors.
      In addition, this procedure has demonstrated reduced relapse rates and similar
      overall survival when compared with unrelated allogeneic hematopoietic stem cell
      transplantation. The limited dose of CD34-positive stem cells available with
      single-unit cord transplantation has been addressed by the development of double
      unit cord transplantation. In combination with improved conditioning regimens,
      double-unit cord transplantation has allowed for the treatment of larger
      children, as well as adult patients with hematological malignancies. Current
      excitement in the field revolves around the development of safer techniques to
      improve homing, engraftment, and immune reconstitution after cord blood
      transplantation. Here the authors review the past, present, and future of cord
      transplantation. 

PMID- 25378656
TI  - The rs738409 (I148M) variant of the PNPLA3 gene and cirrhosis: a meta-analysis.
AB  - The human patatin-like phospholipase domain-containing-3 (PNPLA3) gene rs738409
      C>G polymorphism is associated with several types of liver disease. The aim of
      this meta-analysis was to assess the risk of cirrhosis on the basis of rs738409
      allele frequency and genotype. Medline, the Cochrane Library, EMBASE, and Google
      Scholar were searched for prospective and retrospective studies assessing the
      effect of the rs738409 polymorphism on liver cirrhosis. Seven studies, involving
      2,023 patients with cirrhosis, were included. The G allele was associated with a
      significantly increased risk of cirrhosis versus the C allele [pooled odds ratio
      (OR) = 1.86, 95% confidence interval (CI) = 1.64-2.12, Z = 9.55, P < 0.001]. Both
      the GC and GG genotypes were associated with a significantly increased risk of
      cirrhosis versus the CC genotype (GC vs. CC: pooled OR = 1.73, 95% CI = 1.51
      1.98, Z = 7.86, P < 0.001; GG vs. CC: pooled OR = 3.41, 95% CI = 2.77-4.18, Z =
      11.65, P < 0.001). There was no evidence of publication bias. Our findings
      suggest that patients at risk for liver cirrhosis may benefit from PNPLA3
      genotyping and thus more intensive monitoring if the rs738409 C>G polymorphism is
      identified. 

PMID- 25378657
TI  - Relative roles of ABCG5/ABCG8 in liver and intestine.
AB  - ABCG5 (G5) and ABCG8 (G8) form a sterol transporter that acts in liver and
      intestine to prevent accumulation of dietary sterols. Mutations in either G5 or
      G8 cause sitosterolemia, a recessive disorder characterized by sterol
      accumulation and premature coronary atherosclerosis. Hepatic G5G8 mediates
      cholesterol excretion into bile, but the function and relative importance of
      intestinal G5G8 has not been defined. To determine the role of intestinal G5G8,
      we developed liver-specific (L-G5G8(-/-)), intestine-specific (I-G5G8(-/-)), and
      total (G5G8(-/-)) KO mice. Tissue levels of sitosterol, the most abundant plant
      sterol, were >90-fold higher in G5G8(-/-) mice than in WT animals. Expression of
      G5G8 only in intestine or only in liver decreased tissue sterol levels by 90%
      when compared with G5G8(-/-) animals. Biliary sterol secretion was reduced in L
      G5G8(-/-) and G5G8(-/-) mice, but not in I-G5G8(-/-) mice. Conversely, absorption
      of plant sterols was increased in I-G5G8(-/-) and G5G8(-/-) mice, but not in L
      G5G8(-/-) mice. Reverse cholesterol transport, as assessed from the fraction of
      intravenously administered (3)H-cholesterol that appeared in feces, was reduced
      in G5G8(-/-), I-G5G8(-/-), and L-G5G8(-/-) mice. Thus, G5G8 expression in both
      the liver and intestine protects animals from sterol accumulation, and intestinal
      G5G8 contributes to extrahepatic cholesterol efflux in mice. 

PMID- 25378658
TI  - Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid
      metabolism and atherosclerosis.
AB  - We performed silencing and overexpression studies of flavin containing
      monooxygenase (FMO) 3 in hyperlipidemic mouse models to examine its effects on
      trimethylamine N-oxide (TMAO) levels and atherosclerosis. Knockdown of hepatic
      FMO3 in LDL receptor knockout mice using an antisense oligonucleotide resulted in
      decreased circulating TMAO levels and atherosclerosis. Surprisingly, we also
      observed significant decreases in hepatic lipids and in levels of plasma lipids,
      ketone bodies, glucose, and insulin. FMO3 overexpression in transgenic mice, on
      the other hand, increased hepatic and plasma lipids. Global gene expression
      analyses suggested that these effects of FMO3 on lipogenesis and gluconeogenesis
      may be mediated through the PPARalpha and Kruppel-like factor 15 pathways. In
      vivo and in vitro results were consistent with the concept that the effects were
      mediated directly by FMO3 rather than trimethylamine/TMAO; in particular,
      overexpression of FMO3 in the human hepatoma cell line, Hep3B, resulted in
      significantly increased glucose secretion and lipogenesis. Our results indicate a
      major role for FMO3 in modulating glucose and lipid homeostasis in vivo, and they
      suggest that pharmacologic inhibition of FMO3 to reduce TMAO levels would be
      confounded by metabolic interactions. 

PMID- 25378661
TI  - EPAC2-mediated calreticulin regulates LIF and COX2 expression in human
      endometrial glandular cells.
AB  - The proper production of the implantation-related factors, leukemia inhibitory
      factor (LIF), cyclooxygenase 2 (COX2, PTGS2), and prostaglandin E2 (PGE2) in the
      uterine glands is essential for embryo implantation and the establishment of
      endometrial receptivity. It has been shown that cAMP-mediated protein kinase A
      (PKA) signaling regulates the production of these factors. We have previously
      reported that exchange protein directly activated by cAMP 2 (EPAC2, RAPGEF4),
      another cAMP mediator, is involved in the differentiation of endometrial stromal
      cells through the regulation of the expression of calreticulin (CALR). To address
      whether EPAC2-CALR signaling is involved in the expression of implantation
      related factors, we examined the effect of EPAC2 and CALR knockdown on their
      expression in cultured human endometrial glandular epithelial EM1 cells, treated
      with forskolin, an adenylyl cyclase activator, an EPAC-selective cAMP analog (8
      (4-chlorophenylthio)-2'-O-methyl cAMP (CPT)), or a PKA-selective cAMP analog
      (N(6)-phenyl-cAMP (Phe)). In addition, the status of cell senescence was
      examined. EPAC2 knockdown suppressed the expression of CALR protein and mRNA in
      EM1 cells. Forskolin- or Phe-, but not CPT-, induced expression of LIF or PTGS2
      and secretion of PGE2 was inhibited in EPAC2- or CALR-silenced EM1 cells. In
      addition, knockdown of EPAC2 or CALR increased senescence-associated beta
      galactosidase activity and expression of p21 but decreased expression of p53.
      These findings indicate that expression of CALR regulated by EPAC2 in endometrial
      glandular epithelial cells is critical for the expression of LIF and PTGS2
      mediated production of PGE2 through cAMP signaling. Furthermore, EPAC2 and CALR
      could play a role in the maintenance of gland function. 

PMID- 25378660
TI  - Discordance of HIV and HSV-2 biomarkers and self-reported sexual behaviour among
      orphan adolescents in Western Kenya.
AB  - BACKGROUND: This paper examines the discordance between biological data of HIV
      and herpes simplex virus type 2 (HSV-2) infections and self-reported
      questionnaire responses among orphan adolescents in Western Kenya. METHODS: In
      2011, 837 orphan adolescents from 26 primary schools were enrolled in an HIV
      prevention trial. At baseline, blood samples were drawn for HIV and HSV-2
      infection biomarker testing, and participants completed an audio computer
      assisted self-interviewing survey. RESULTS: Comparing biological data with self
      reported responses indicated that 70% of HIV-positive (7 out of 10) and 64% of
      HSV-2-positive (18 out of 28 positive) participants reported never having had
      sex. Among ever-married adolescents, 65% (57 out of 88) reported never having had
      sex. Overall, 10% of study participants appeared to have inconsistently reported
      their sexual behaviour. Logistic regression analyses indicated that lower
      educational level and exam scores were significant predictors of inconsistent
      reporting. CONCLUSIONS: Our study demonstrates the discordance between infections
      measured by biomarkers and self-reports of having had sex among orphan
      adolescents in Kenya. In order to detect programme effects accurately in
      prevention research, it is necessary to collect both baseline and endline
      biological data. Furthermore, it is recommended to triangulate multiple data
      sources about adolescent participants' self-reported information about marriage
      and pregnancies from school records and parent/guardians to verify the
      information. Researchers should recognise potential threats to validity in data
      and design surveys to consider cognitive factors and/or cultural context to
      obtain more accurate and reliable information from adolescents regarding
      HIV/sexually transmitted infection risk behaviours. CLINICAL TRAIL REGISTRATION
      NUMBER: NCT01501864.

PMID- 25378662
TI  - Cement pulmonary embolism after percutaneous vertebroplasty in multiple myeloma.

PMID- 25378659
TI  - Genetic loci associated with circulating levels of very long-chain saturated
      fatty acids.
AB  - Very long-chain saturated fatty acids (VLSFAs) are saturated fatty acids with 20
      or more carbons. In contrast to the more abundant saturated fatty acids, such as
      palmitic acid, there is growing evidence that circulating VLSFAs may have
      beneficial biological properties. Whether genetic factors influence circulating
      levels of VLSFAs is not known. We investigated the association of common genetic
      variation with plasma phospholipid/erythrocyte levels of three VLSFAs by
      performing genome-wide association studies in seven population-based cohorts
      comprising 10,129 subjects of European ancestry. We observed associations of
      circulating VLSFA concentrations with common variants in two genes, serine
      palmitoyl-transferase long-chain base subunit 3 (SPTLC3), a gene involved in the
      rate-limiting step of de novo sphingolipid synthesis, and ceramide synthase 4
      (CERS4). The SPTLC3 variant at rs680379 was associated with higher arachidic acid
      (20:0 , P = 5.81 * 10(-13)). The CERS4 variant at rs2100944 was associated with
      higher levels of 20:0 (P = 2.65 * 10(-40)) and in analyses that adjusted for
      20:0, with lower levels of behenic acid (P = 4.22 * 10(-26)) and lignoceric acid
      (P = 3.20 * 10(-21)). These novel associations suggest an inter-relationship of
      circulating VLSFAs and sphingolipid synthesis. 

PMID- 25378663
TI  - Delayed dorsal scapular artery pseudoaneurysm rupture after blunt chest injury.

PMID- 25378664
TI  - Diffuse left coronary artery fistulae.

PMID- 25378665
TI  - Reference intervals - ever met a normal person?

PMID- 25378666
TI  - The use of echocardiography in acute cardiovascular care: Recommendations of the
      European Association of Cardiovascular Imaging and the Acute Cardiovascular Care
      Association.
AB  - Echocardiography is one of the most powerful diagnostic and monitoring tools
      available to the modern emergency/critical care practitioner. Currently, there is
      a lack of specific European Association of Cardiovascular Imaging/Acute
      Cardiovascular Care Association recommendations for the use of echocardiography
      in acute cardiovascular care. In this document, we describe the practical
      applications of echocardiography in patients with acute cardiac conditions, in
      particular with acute chest pain, acute heart failure, suspected cardiac
      tamponade, complications of myocardial infarction, acute valvular heart disease
      including endocarditis, acute disease of the ascending aorta and post
      intervention complications. Specific issues regarding echocardiography in other
      acute cardiovascular care scenarios are also described.

PMID- 25378668
TI  - Frequent occurrence of cerebral demyelination in adrenomyeloneuropathy.
AB  - OBJECTIVE: To study the frequency of additional cerebral demyelination in Dutch
      patients with adrenomyeloneuropathy (AMN). METHODS: Consecutive patients with AMN
      from the Dutch X-linked adrenoleukodystrophy cohort without cerebral
      demyelination on MRI at inclusion, seen between January 1, 1992, and January 1,
      1999, were included. Primary endpoints were brain involvement, death, or the end
      of follow-up on January 1, 2011. Three levels of certainty were used for cerebral
      demyelination: (1) signs and symptoms reported by relatives and treating
      physicians, confirmed by brain MRI; if follow-up MRIs were not available, (2)
      based upon information from treating physicians and relatives, and (3) based upon
      information obtained from relatives only. Results were compared with a study
      published in 2001, in which 13/68 (19.1%) patients with AMN developed cerebral
      demyelination in 9.5 +/- 5.5 years. Differences of the proportions of patients
      with cerebral demyelination and their 95% confidence intervals (CIs) were
      calculated. RESULTS: Of 27 patients with AMN, 17 (63%) developed cerebral
      demyelination 10.2 +/- 6.9 years after onset of myelo(neuro)pathy. Mean survival
      was 3.4 +/- 2.9 years. Brain involvement was higher in Dutch patients with AMN
      (difference 44%, 95% CI 0.23-0.64). CONCLUSIONS: Cerebral demyelination in AMN
      may be more frequent than previously reported. Survival is as poor as in
      childhood cerebral adrenoleukodystrophy. Therapies that can halt cerebral
      demyelination in these patients are needed.

PMID- 25378667
TI  - Onset of multiple sclerosis before adulthood leads to failure of age-expected
      brain growth.
AB  - OBJECTIVE: To determine the impact of pediatric-onset multiple sclerosis (MS) on
      age-expected brain growth. METHODS: Whole brain and regional volumes of 36
      patients with relapsing-remitting MS onset prior to 18 years of age were
      segmented in 185 longitudinal MRI scans (2-11 scans per participant, 3-month to 2
      year scan intervals). MRI scans of 25 age- and sex-matched healthy normal
      controls (NC) were also acquired at baseline and 2 years later on the same
      scanner as the MS group. A total of 874 scans from 339 participants from the NIH
      funded MRI study of normal brain development acquired at 2-year intervals were
      used as an age-expected healthy growth reference. All data were analyzed with an
      automatic image processing pipeline to estimate the volume of brain and brain
      substructures. Mixed-effect models were built using age, sex, and group as fixed
      effects. RESULTS: Significant group and age interactions were found with the
      adjusted models fitting brain volumes and normalized thalamus volumes (p < 10(
      4)). These findings indicate a failure of age-normative brain growth for the MS
      group, and an even greater failure of thalamic growth. In patients with MS, T2
      lesion volume correlated with a greater reduction in age-expected thalamic
      volume. To exclude any scanner-related influence on our data, we confirmed no
      significant interaction of group in the adjusted models between the NC and NIH
      MRI Study of Normal Brain Development groups. CONCLUSIONS: Our results provide
      evidence that the onset of MS during childhood and adolescence limits age
      expected primary brain growth and leads to subsequent brain atrophy, implicating
      an early onset of the neurodegenerative aspect of MS.

PMID- 25378669
TI  - VZV brainstem encephalitis triggers NMDA receptor immunoreaction.

PMID- 25378670
TI  - Preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs and 30-day
      stroke mortality.
AB  - OBJECTIVES: To examine whether preadmission use of nonaspirin nonsteroidal anti
      inflammatory drugs (NSAIDs) influenced 30-day stroke mortality. METHODS: We
      conducted a nationwide population-based cohort study. Using medical databases, we
      identified all first-time stroke hospitalizations in Denmark between 2004 and
      2012 (n = 100,043) and subsequent mortality. We categorized NSAID use as current
      (prescription redemption within 60 days before hospital admission), former, and
      nonuse. Current use was further classified as new or long-term use. Cox
      regression was used to compute hazard ratios (HRs) of death within 30 days,
      controlling for potential confounding through multivariable adjustment and
      propensity score matching. RESULTS: The adjusted HR of death for ischemic stroke
      was 1.19 (95% confidence interval [CI]: 1.02-1.38) for current users of selective
      cyclooxygenase (COX)-2 inhibitors compared with nonusers, driven by the effect
      among new users (1.42, 95% CI: 1.14-1.77). Comparing the different COX-2
      inhibitors, the HR was driven by new use of older traditional COX-2 inhibitors
      (1.42, 95% CI: 1.14-1.78) among which it was 1.53 (95% CI: 1.02-2.28) for
      etodolac and 1.28 (95% CI: 0.98-1.68) for diclofenac. The propensity score
      matched analysis supported the association between older COX-2 inhibitors and
      ischemic stroke mortality. There was no association for former users. Mortality
      from intracerebral hemorrhage was not associated with use of nonselective NSAIDs
      or COX-2 inhibitors. CONCLUSIONS: Preadmission use of COX-2 inhibitors was
      associated with increased 30-day mortality after ischemic stroke, but not
      hemorrhagic stroke. Use of nonselective NSAIDs at time of admission was not
      associated with mortality from ischemic stroke or intracerebral hemorrhage.

PMID- 25378671
TI  - Vitamin D deficiency predicts cognitive decline in older men and women: The
      Pro.V.A. Study.
AB  - OBJECTIVE: To test the hypothesis that hypovitaminosis D is associated with a
      higher risk of cognitive decline over a 4.4-year follow-up in a large sample of
      older adults. METHODS: This research was part of the Progetto Veneto Anziani
      (Pro.V.A.), an Italian population-based cohort study of 1,927 elderly subjects.
      Serum 25-hydroxyvitamin D (25OHD) levels were measured at the baseline. Global
      cognitive function was measured with the Mini-Mental State Examination (MMSE);
      scores lower than 24 were indicative of cognitive dysfunction, and a decline of 3
      or more points on the MMSE over the follow-up was considered as clinically
      significant. Analyses were adjusted for relevant confounders, including health
      and performance status. RESULTS: Participants with 25OHD deficiency (<50 nmol/L)
      or insufficiency (50-75 nmol/L) were more likely to have declining MMSE scores
      during the follow-up than those who were 25OHD sufficient (>=75 nmol/L). Among
      participants cognitively intact (baseline MMSE scores >=24 and without diagnosis
      of dementia), the multivariate adjusted relative risk (95% confidence interval
      [CI]) of the onset of cognitive dysfunction was 1.36 (95% CI: 1.04-1.80; p =
      0.02) for those with vitamin D deficiency and 1.29 (95% CI: 1.00-1.76; p = 0.05)
      for those with vitamin D insufficiency by comparison with individuals with normal
      25OHD levels. CONCLUSION: The results of our study support an independent
      association between low 25OHD levels and cognitive decline in elderly
      individuals. In cognitively intact elderly subjects, 25OHD levels below 75 nmol/L
      are already predictive of global cognitive dysfunction at 4.4 years.

PMID- 25378672
TI  - Adiponectin and leptin levels in migraineurs in the Atherosclerosis Risk in
      Communities Study.
AB  - OBJECTIVE: To evaluate adiponectin and leptin levels in older men and women with
      migraine. METHODS: Fasting total and high molecular weight (HMW) adiponectin and
      leptin levels were evaluated in a case-cohort study of nondiabetic older migraine
      and nonmigraine control participants from the ongoing, longitudinal, general
      population, Atherosclerosis Risk in Communities Study at visit 1 (1987-1989). A
      standardized headache questionnaire was completed at visit 3 (1993-1995).
      Logistic regression models adjusted for age, sex, race, center, body mass index,
      and fasting glucose were used to evaluate the association of each adipocytokine
      with migraine. RESULTS: Of the 981 participants, the mean age at baseline was
      52.8 years (SE 0.3); 131 fulfilled migraine criteria. Crude, mean total
      adiponectin levels were greater in men and women with migraine (8.1 ug/mL, SE
      0.5) as compared to those without migraine (7.0 ug/mL, SE 0.2) (p = 0.031). After
      adjustments, the odds of migraine were increased by 88% with each SD increase in
      total adiponectin in men (odds ratio [OR] 1.86; 95% confidence interval [CI]
      1.15, 3.01; p = 0.011), but not in women (OR 1.05; 95% CI 0.80, 1.37; p = 0.728;
      p interaction = 0.029). Similar results were demonstrated for HMW adiponectin.
      Crude and adjusted leptin levels were not associated with migraine. CONCLUSIONS:
      Although crude, total adiponectin levels were higher in older men and women with
      migraine than controls, after adjustments, the prevalence of migraine was
      significantly associated with total adiponectin only in older men, suggesting the
      association may be confounded or absent in older women. Leptin was not associated
      with migraine in older men or women.

PMID- 25378673
TI  - LRRK2 exonic variants and risk of multiple system atrophy.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between common
      exonic variants in the leucine-rich repeat kinase 2 (LRRK2) gene and risk of
      multiple system atrophy (MSA). METHODS: One series from the United States (92
      patients with pathologically confirmed MSA, 416 controls) and a second series
      from the United Kingdom (85 patients with pathologically confirmed MSA, 352
      controls) were included in this case-control study. We supplemented these data
      with those of 53 patients from the United States with clinically probable or
      possible MSA. Seventeen common LRRK2 exonic variants were genotyped and assessed
      for association with MSA. RESULTS: In the combined series of 177 patients with
      pathologically confirmed MSA and 768 controls, there was a significant
      association between LRRK2 p.M2397T and MSA (odds ratio [OR] = 0.60, p = 0.002).
      This protective effect was observed more strongly in the US series (OR = 0.46, p
      = 0.0008) than the UK series (OR = 0.82, p = 0.41). We observed other noteworthy
      associations with MSA for p.G1624G (OR = 0.63, p = 0.006) and p.N2081D (OR =
      0.15, p = 0.010). The p.G1624G-M2397T haplotype was significantly associated with
      MSA in the US series (p < 0.0001) and combined series (p = 0.003) but not the UK
      series (p = 0.67). Results were consistent when additionally including the US
      patients with clinical MSA, where the strongest single-variant association was
      again observed for p.M2397T (OR = 0.59, p = 0.0005). CONCLUSIONS: These findings
      provide evidence that LRRK2 exonic variants may contribute to susceptibility to
      MSA. Validation in other series and meta-analytic studies will be important.

PMID- 25378674
TI  - Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after
      melphalan and SCT.
AB  - OBJECTIVE: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset
      myopathy that progresses subacutely. If associated with a monoclonal gammopathy
      of unknown significance (MGUS), the outcome is unfavorable: the majority of these
      patients die within 1 to 5 years of respiratory failure. This study aims to
      qualitatively assess the long-term treatment effect of high-dose melphalan (HDM)
      followed by autologous stem cell transplantation (SCT) in a series of 8 patients
      with SLONM-MGUS. METHODS: We performed a retrospective case series study (n = 8)
      on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT
      (HDM-SCT) on survival, muscle strength, and functional capacities. RESULTS: Seven
      patients showed a lasting moderate-good clinical response, 2 of them after the
      second HDM-SCT. All of them had a complete, a very good partial, or a partial
      hematologic response. One patient showed no clinical or hematologic response and
      died. CONCLUSIONS: This case series shows the positive effect of HDM-SCT in this
      rare disorder. Factors that may portend an unfavorable outcome are a long disease
      course before the hematologic treatment and a poor hematologic response. Age at
      onset, level and type of M protein (kappa vs lambda), and severity of muscle
      weakness were not associated with a specific outcome. CLASSIFICATION OF EVIDENCE:
      This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT
      increases the probability of survival and functional improvement.

PMID- 25378675
TI  - The speed of ultraearly hematoma growth in acute intracerebral hemorrhage.
AB  - OBJECTIVE: The prognostic importance of the speed of early hematoma growth in
      acute intracerebral hemorrhage (ICH) has not been well established. We aimed to
      determine the association between the rate of increase in hematoma volume and
      major clinical outcomes in the Intensive Blood Pressure Reduction in Acute
      Cerebral Hemorrhage Trial (INTERACT) studies. The effects of early intensive
      blood pressure (BP) lowering according to the speed of hematoma growth were also
      investigated. METHODS: Pooled analyses of the INTERACT1 (n = 404) and INTERACT2
      (n = 2,839) studies-randomized controlled trials of patients with spontaneous ICH
      with elevated systolic BP, randomly assigned to intensive (target systolic BP
      <140 mm Hg) or guideline-based (<180 mm Hg) BP management. The speed of
      ultraearly hematoma growth (UHG) was defined as hematoma volume (mL)/onset-to-CT
      time (hours). Primary outcome was death or major disability (modified Rankin
      Scale score of 3-6) at 90 days. RESULTS: Among a total of 2,909 patients (90%)
      with information on UHG and outcome, median speed of UHG was 6.2 mL/h. There was
      a linear association between UHG and outcome: multivariable-adjusted odd ratios
      1.90 (95% confidence interval 1.50-2.39) for 5-10 mL/h and 2.96 (2.36-3.71) for
      >10 mL/h vs the <5 mL/h group. There were no clear differences in the effects of
      intensive BP lowering according to 3 speeds of UHG on outcome (p = 0.75 for
      homogeneity). CONCLUSIONS: The speed of UHG in patients with ICH was continuously
      associated with increased risks of death or major disability, and from lower
      levels than previously reported (>=5 mL/h). The benefits of intensive BP lowering
      appear to be independent of the speed of bleeding.

PMID- 25378676
TI  - Reevaluating clinical measurement tools in therapeutic trials: time to make a
      Rasch decision?

PMID- 25378678
TI  - To revitalize neurology we need to address physician burnout.

PMID- 25378677
TI  - Changing outcome in inflammatory neuropathies: Rasch-comparative responsiveness.
AB  - OBJECTIVES: We performed responsiveness comparison between the patient-reported
      Inflammatory Rasch-built Overall Disability Scale (I-RODS) and the widely used
      clinician-reported Inflammatory Neuropathy Cause and Treatment-Overall Neuropathy
      Limitation Scale (INCAT-ONLS) in patients with Guillain-Barre syndrome (GBS),
      chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and
      immunoglobulin M-monoclonal gammopathy of undetermined significance related
      polyneuropathy (IgM-MGUSP). METHODS: One hundred thirty-seven patients (GBS: 55,
      CIDP: 59, IgM-MGUSP: 23) with a new diagnosis or clinical relapse assessed both
      scales. Patients with GBS/CIDP were examined at 0, 1, 3, 6, and 12 months;
      patients with IgM-MGUSP at 0, 3, and 12. We subjected all data to Rasch analyses,
      and calculated for each patient the magnitude of change on both scales using the
      minimal clinically important difference (MCID) related to the individual standard
      errors (SEs). A responder was defined as having an MCID-SE >=1.96. Individual
      scores on both measures were correlated with the EuroQoL thermometer (heuristic
      responsiveness). RESULTS: The I-RODS showed a significantly higher proportion of
      meaningful improvement compared with the INCAT-ONLS findings in GBS/CIDP. For IgM
      MGUSP, the lack of responsiveness during the 1-year study did not allow a clear
      separation. Heuristic responsiveness was consistently higher with the I-RODS.
      CONCLUSION: The I-RODS more often captures clinically meaningful changes over
      time, with a greater magnitude of change, compared with the INCAT-ONLS disability
      scale in patients with GBS and CIDP. The I-RODS offers promise for being a more
      sensitive measure and its use is therefore suggested in future trials involving
      patients with GBS and CIDP.

PMID- 25378679
TI  - Physician burnout: A neurologic crisis.
AB  - The prevalence of burnout is higher in physicians than in other professions and
      is especially high in neurologists. Physician burnout encompasses 3 domains: (1)
      emotional exhaustion: the loss of interest and enthusiasm for practice; (2)
      depersonalization: a poor attitude with cynicism and treating patients as
      objects; and (3) career dissatisfaction: a diminished sense of personal
      accomplishment and low self-value. Burnout results in reduced work hours,
      relocation, depression, and suicide. Burned-out physicians harm patients because
      they lack empathy and make errors. Studies of motivational factors in the
      workplace suggest several preventive interventions: (1) Provide counseling for
      physicians either individually or in groups with a goal of improving adaptive
      skills to the stress and rapid changes in the health care environment. (2)
      Identify and eliminate meaningless required hassle factors such as electronic
      health record "clicks" or insurance mandates. (3) Redesign practice to remove
      pressure to see patients in limited time slots and shift to team-based care. (4)
      Create a culture that promotes career advancement, mentoring, and recognition of
      accomplishments. 

PMID- 25378680
TI  - Inflaming the need for migraine biomarkers.

PMID- 25378681
TI  - Impact of MS during the critical window of brain development.

PMID- 25378682
TI  - Late-stage CTE pathology in a retired soccer player with dementia.

PMID- 25378683
TI  - Association between electronic cigarette use and openness to cigarette smoking
      among US young adults.
AB  - INTRODUCTION: Use of electronic nicotine delivery systems (ENDS), including
      electronic cigarettes (e-cigarettes), is increasing. One concern is the appeal of
      these products to youth and young adults and the potential to influence
      perceptions and use of conventional cigarettes. METHODS: Using data from the 2012
      2013 National Adult Tobacco Survey, characteristics of adults aged 18-29 years
      who had never established cigarette smoking behavior were examined by ever use of
      e-cigarettes, demographics, and ever use of other tobacco products (smokeless
      tobacco, cigars, hookah, and cigarettes). Multivariate logistic regression was
      used to examine the relationship between e-cigarette use and openness to
      cigarette smoking among young adults, defined as the lack of a firm intention not
      to smoke soon or in the next year. RESULTS: Among young adults who had never
      established cigarette smoking behavior (unweighted n = 4,310), 7.9% reported
      having ever tried e-cigarettes, and 14.6% of those who reported having ever tried
      e-cigarettes also reported current use of the product. Ever e-cigarette use was
      associated with being open to cigarette smoking (adjusted odds ratio = 2.4; 95%
      confidence interval = 1.7, 3.3), as was being male, aged 18-24 years, less
      educated, and having ever used hookah or experimented with conventional
      cigarettes. CONCLUSIONS: Ever use of e-cigarettes and other tobacco products was
      associated with being open to cigarette smoking. This study does not allow us to
      assess the directionality of this association, so future longitudinal research is
      needed to illuminate tobacco use behaviors over time as well as provide
      additional insight on the relationship between ENDS use and conventional
      cigarette use among young adult populations.

PMID- 25378684
TI  - Arabinoxylan in wheat is more responsible than cellulose for promoting intestinal
      barrier function in weaned male piglets.
AB  - BACKGROUND: The effect of dietary fiber on intestinal function primarily has been
      ascribed to its interaction with intestinal bacteria in the hindgut, whereas
      changes in intestinal bacteria in the host have been considered to depend on
      fiber composition. OBJECTIVES: The objectives of this study were to determine the
      contribution of the major fiber components to the health-promoting effects of
      wheat bran on intestinal mucosal barrier function and to elucidate the
      involvement of microbiota changes in weaned piglets. METHODS: Thirty freshly
      weaned male piglets were assigned to 5 dietary treatment groups (n = 6) according
      to litter and weight. The piglets consumed synthetic diets ad libitum for 30 d,
      including a basal control diet (CON) without fiber components, a wheat bran diet
      (WB) as reference diet (10% wheat bran), and 3 other diets containing amounts of
      fiber components equivalent to those in the WB, i.e., an arabinoxylan diet (AX),
      a cellulose diet (CEL), and a combined arabinoxylan and cellulose diet (CB).
      RESULTS: The groups consuming diets containing arabinoxylans (i.e., the WB, AX,
      and CB groups) had increased intestinal secretory immunoglobulin A
      concentrations, goblet cell number and cecal short-chain fatty acid
      concentrations, and reduced branched-chain fatty acid concentrations and pH
      values compared with the CON group. In the WB group, the stimulated secretion of
      Cl(-) was suppressed (60.8% and 47.5% change in short-circuit current caused by
      theophylline and carbachol, respectively) in the distal small intestine compared
      with the CON group. The AX and CB groups also had increased intestinal alkaline
      phosphatase activities and reduced intestinal transcellular permeability (by
      77.3% and 67.2%, respectively) compared with the CON group. Meanwhile, in the WB
      group, cecal Bacteroidetes and Enterobacteriaceae populations were lower, and the
      growth of Lactobacillus was higher in the AX and CB groups than in the CON group,
      whereas no positive effect on intestinal barrier function was observed in the CEL
      group. CONCLUSION: Arabinoxylan in wheat bran, and not cellulose, is mainly
      responsible for improving various functional components of the intestinal barrier
      function and the involvement of microbiota changes.

PMID- 25378685
TI  - Optimal serum selenium concentrations are associated with lower depressive
      symptoms and negative mood among young adults.
AB  - BACKGROUND: There is evidence that low, and possibly high, selenium status is
      associated with depressed mood. More evidence is needed to determine whether this
      pattern occurs in young adults with a wide range of serum concentrations of
      selenium. OBJECTIVE: The aim of this study was to determine if serum selenium
      concentration is associated with depressive symptoms and daily mood states in
      young adults. METHODS: A total of 978 young adults (aged 17-25 y) completed the
      Center for Epidemiological Studies-Depression scale and reported their negative
      and positive mood daily for 13 d using an Internet diary. Serum selenium
      concentration was determined by inductively coupled plasma mass spectrometry.
      ANCOVA and regression models tested the linear and curvilinear associations
      between decile of serum selenium concentration and mood outcomes, controlling for
      age, gender, ethnicity, BMI, and weekly alcohol intake. Smoking and childhood
      socioeconomic status were further controlled in a subset of participants.
      RESULTS: The mean +/- SD serum selenium concentration was 82 +/- 18 MUg/L and
      ranged from 49 to 450 MUg/L. Participants with the lowest serum selenium
      concentration (62 +/- 4 MUg/L; decile 1) and, to a lesser extent, those with the
      highest serum selenium concentration (110 +/- 38 MUg/L; decile 10) had
      significantly greater adjusted depressive symptoms than did participants with
      midrange serum selenium concentrations (82 +/- 1 to 85 +/- 1 MUg/L; deciles 6 and
      7). Depressive symptomatology was lowest at a selenium concentration of ~85
      MUg/L. Patterns for negative mood were similar but more U-shaped. Positive mood
      showed an inverse U-shaped association with selenium, but this pattern was less
      consistent than depressive symptoms or negative mood. CONCLUSIONS: In young
      adults, an optimal range of serum selenium between ~82 and 85 MUg/L was
      associated with reduced risk of depressive symptomatology. This range
      approximates the values at which glutathione peroxidase is maximal, suggesting
      that future research should investigate antioxidant pathways linking selenium to
      mood. This trial was registered with the Australian New Zealand Clinical Trials
      Registry as ACTRN12613000773730.

PMID- 25378686
TI  - The major facilitator superfamily transporter ZIFL2 modulates cesium and
      potassium homeostasis in Arabidopsis.
AB  - Potassium (K(+)) is an essential mineral nutrient for plant growth and
      development, with numerous membrane transporters and channels having been
      implicated in the maintenance and regulation of its homeostasis. The cation
      cesium (Cs(+)) is toxic for plants but shares similar chemical properties to the
      K(+) ion and hence competes with its transport. Here, we report that K(+) and
      Cs(+) homeostasis in Arabidopsis thaliana also requires the action of ZIFL2 (Zinc
      Induced Facilitator-Like 2), a member of the Major Facilitator Superfamily (MFS)
      of membrane transporters. We show that the Arabidopsis ZIFL2 is a functional
      transporter able to mediate K(+) and Cs(+) influx when heterologously expressed
      in yeast. Promoter-reporter, reverse transcription-PCR and fluorescent protein
      fusion experiments indicate that the predominant ZIFL2.1 isoform is targeted to
      the plasma membrane of endodermal and pericyle root cells. ZIFL2 loss of function
      and overexpression exacerbate and alleviate plant sensitivity, respectively, upon
      Cs(+) and excess K(+) supply, also influencing Cs(+) whole-plant partitioning. We
      propose that the activity of this Arabidopsis MFS carrier promotes cellular K(+)
      efflux in the root, thereby restricting Cs(+)/K(+) xylem loading and subsequent
      root to shoot translocation under conditions of Cs(+) or high K(+) external
      supply.

PMID- 25378687
TI  - Apple fruit copper amine oxidase isoforms: peroxisomal MdAO1 prefers diamines as
      substrates, whereas extracellular MdAO2 exclusively utilizes monoamines.
AB  - 4-Aminobutyrate (GABA) accumulates in apple fruit during controlled atmosphere
      storage. A potential source of GABA is the polyamine putrescine, which can be
      oxidized via copper-containing amine oxidase (CuAO), resulting in the production
      4-aminobutanal/Delta(1)-pyrroline, with the consumption of O2 and release of H2O2
      and ammonia. Five putative CuAO genes (MdAO genes) were cloned from apple (Malus
      domestica Borkh. cv. Empire) fruit, and the deduced amino acid sequences found to
      contain the active sites typically conserved in CuAOs. Genes encoding two of
      these enzymes, MdAO1 and MdAO2, were highly expressed in apple fruit and selected
      for further analysis. Amino acid sequence analysis predicted the presence of a C
      terminal peroxisomal targeting signal 1 tripeptide in MdAO1 and an N-terminal
      signal peptide and N-glycosylation site in MdAO2. Transient expression of green
      fluorescent fusion proteins in Arabidopsis protoplasts or onion epidermal cells
      revealed a peroxisomal localization for MdAO1 and an extracellular localization
      for MdAO2. The enzymatic activities of purified recombinant MdAO1 and MdAO2 were
      measured continuously as H2O2 production using a coupled reaction. MdAO1 did not
      use monoamines or polyamines and displayed high catalytic efficiency for 1,3
      diaminopropane, putrescine and cadaverine, whereas MdAO2 exclusively utilized
      aliphatic and aromatic monoamines, including 2-phenylethylamine and tyramine.
      Together, these results indicate that MdAO1 may contribute to GABA production via
      putrescine oxidation in the peroxisome of apple fruit under controlled atmosphere
      conditions. MdAO2 seems to be involved in deamination of 2-phenylethylamine,
      which is a step in the biosynthesis of 2-phenylethanol, a contributor to fruit
      flavor and flower fragrance.

PMID- 25378688
TI  - Jasmonates induce both defense responses and communication in monocotyledonous
      and dicotyledonous plants.
AB  - Jasmonic acid (JA) and its derivatives (jasmonates, JAs) are phytohormones with
      essential roles in plant defense against pathogenesis and herbivorous arthropods.
      Both the up- and down-regulation of defense responses are dependent on signaling
      pathways mediated by JAs as well as other stress hormones (e.g. salicylic acid),
      generally those involving the transcriptional and post-transcriptional regulation
      of transcription factors via protein modification and epigenetic regulation. In
      addition to the typical model plant Arabidopsis (a dicotyledon), advances in
      genetics research have made rice a model monocot in which innovative pest control
      traits can be introduced and whose JA signaling pathway can be studied. In this
      review, we introduce the dynamic functions of JAs in plant defense strategy using
      defensive substances (e.g. indole alkaloids and terpenoid phytoalexins) and
      airborne signals (e.g. green leaf volatiles and volatile terpenes) in response to
      biotrophic and necrotrophic pathogens as well as above-ground and below-ground
      herbivores. We then discuss the important issue of how the mutualism of
      herbivorous arthropods with viruses or bacteria can cause cross-talk between JA
      and other phytohormones to counter the defense systems.

PMID- 25378689
TI  - Whole-genome analysis of herbicide-tolerant mutant rice generated by
      Agrobacterium-mediated gene targeting.
AB  - Gene targeting (GT) is a technique used to modify endogenous genes in target
      genomes precisely via homologous recombination (HR). Although GT plants are
      produced using genetic transformation techniques, if the difference between the
      endogenous and the modified gene is limited to point mutations, GT crops can be
      considered equivalent to non-genetically modified mutant crops generated by
      conventional mutagenesis techniques. However, it is difficult to guarantee the
      non-incorporation of DNA fragments from Agrobacterium in GT plants created by
      Agrobacterium-mediated GT despite screening with conventional Southern blot
      and/or PCR techniques. Here, we report a comprehensive analysis of herbicide
      tolerant rice plants generated by inducing point mutations in the rice ALS gene
      via Agrobacterium-mediated GT. We performed genome comparative genomic
      hybridization (CGH) array analysis and whole-genome sequencing to evaluate the
      molecular composition of GT rice plants. Thus far, no integration of
      Agrobacterium-derived DNA fragments has been detected in GT rice plants. However,
      >1,000 single nucleotide polymorphisms (SNPs) and insertion/deletion (InDels)
      were found in GT plants. Among these mutations, 20-100 variants might have some
      effect on expression levels and/or protein function. Information about additive
      mutations should be useful in clearing out unwanted mutations by backcrossing.

PMID- 25378690
TI  - Strategies for optimization of mineral nutrient transport in plants: multilevel
      regulation of nutrient-dependent dynamics of root architecture and transporter
      activity.
AB  - How do sessile plants cope with irregularities in soil nutrient availability? The
      uptake of essential minerals from the soil influences plant growth and
      development. However, most environments do not provide sufficient nutrients;
      rather nutrient distribution in the soil can be uneven and change temporally
      according to environmental factors. To maintain mineral nutrient homeostasis in
      their tissues, plants have evolved sophisticated systems for coping with spatial
      and temporal variability in soil nutrient concentrations. Among these are
      mechanisms for modulating root system architecture in response to nutrient
      availability. This review discusses recent advances in knowledge of the two
      important strategies for optimizing nutrient uptake and translocation in plants:
      root architecture modification and transporter expression control in response to
      nutrient availability. Recent studies have determined (i) nutrient-specific root
      patterns; (ii) their physiological consequences; and (iii) the molecular
      mechanisms underlying these modulation systems that operate to facilitate
      efficient nutrient acquisition. Another mechanism employed by plants in nutrient
      heterogeneous soils involves modification of nutrient transport activities in a
      nutrient concentration-dependent manner. In recent years, considerable progress
      has been made in characterizing the diverse functions of transporters for
      specific nutrients; it is now clear that the expression and activities of
      nutrient transporters are finely regulated in multiple steps at both the
      transcriptional and post-transcriptional levels for adaptation to a wide range of
      nutrient conditions. 

PMID- 25378691
TI  - Identification of a unique 2-oxoglutarate-dependent flavone 7-O-demethylase
      completes the elucidation of the lipophilic flavone network in basil.
AB  - Small molecule demethylation is considered unusual in plants. Of the studied
      instances, the N-demethylation of nicotine is catalyzed by a Cyt P450
      monooxygenase, while the O-dealkylation of alkaloids in Papaver somniferum is
      mediated by 2-oxoglutarate-dependent dioxygenases (2-ODDs). This report describes
      a 2-ODD regiospecifically catalyzing the 7-O-demethylation of methoxylated
      flavones in peltate trichomes of sweet basil (Ocimum basilicum L.). Three
      candidate 2-ODDs were identified in the basil trichome transcriptome database.
      Only the candidate designated ObF7ODM1 was found to be active with and highly
      specific for the proposed natural substrates, gardenin B and 8-hydroxysalvigenin.
      Of the characterized 2-ODDs, ObF7ODM1 is most closely related to O-demethylases
      from Papaver. The demethylase activity in trichomes from four basil chemotypes
      matches well with the abundance of ObF7ODM1 peptides and transcripts in the same
      trichome preparations. Treatment of basil plants with a 2-ODD inhibitor
      prohexadione-calcium significantly reduced the accumulation of 7-O-demethylated
      flavone nevadensin, confirming the involvement of a 2-ODD in its formation.
      Notably, the full-length open reading frame of ObF7ODM1 contains a second in
      frame AUG codon 57 nucleotides downstream of the first translation initiation
      codon. Both AUG codons are recognized by bacterial translation machinery during
      heterologous gene expression. The N-truncated ObF7ODM1 is nearly inactive. The N
      terminus essential for activity is unique to ObF7ODM1 and does not align with the
      sequences of other 2-ODDs. Further studies will reveal whether alternative
      translation initiation plays a role in regulating the O-demethylase activity in
      planta. Molecular identification of the flavone 7-O-demethylase completes the
      biochemical elucidation of the lipophilic flavone network in basil.

PMID- 25378692
TI  - Transgenic perturbation of the decarboxylation phase of Crassulacean acid
      metabolism alters physiology and metabolism but has only a small effect on
      growth.
AB  - Mitochondrial NAD-malic enzyme (ME) and/or cytosolic/plastidic NADP-ME combined
      with the cytosolic/plastidic pyruvate orthophosphate dikinase (PPDK) catalyze two
      key steps during light-period malate decarboxylation that underpin secondary
      CO(2) fixation in some Crassulacean acid metabolism (CAM) species. We report the
      generation and phenotypic characterization of transgenic RNA interference lines
      of the obligate CAM species Kalanchoe fedtschenkoi with reduced activities of NAD
      ME or PPDK. Transgenic line rNAD-ME1 had 8%, and rPPDK1 had 5% of the wild-type
      level of activity, and showed dramatic changes in the light/dark cycle of CAM
      CO(2) fixation. In well-watered conditions, these lines fixed all of their CO(2)
      in the light; they thus performed C(3) photosynthesis. The alternative malate
      decarboxylase, NADP-ME, did not appear to compensate for the reduction in NAD-ME,
      suggesting that NAD-ME was the key decarboxylase for CAM. The activity of other
      CAM enzymes was reduced as a consequence of knocking out either NAD-ME or PPDK
      activity, particularly phosphoenolpyruvate carboxylase (PPC) and PPDK in rNAD
      ME1. Furthermore, the circadian clock-controlled phosphorylation of PPC in the
      dark was reduced in both lines, especially in rNAD-ME1. This had the consequence
      that circadian rhythms of PPC phosphorylation, PPC kinase transcript levels and
      activity, and the classic circadian rhythm of CAM CO(2) fixation were lost, or
      dampened toward arrhythmia, under constant light and temperature conditions.
      Surprisingly, oscillations in the transcript abundance of core circadian clock
      genes also became arrhythmic in the rNAD-ME1 line, suggesting that perturbing CAM
      in K. fedtschenkoi feeds back to perturb the central circadian clock.

PMID- 25378693
TI  - Direct x-ray microtomography observation confirms the induction of embolism upon
      xylem cutting under tension.

PMID- 25378694
TI  - Malate synthesis and secretion mediated by a manganese-enhanced malate
      dehydrogenase confers superior manganese tolerance in Stylosanthes guianensis.
AB  - Manganese (Mn) toxicity is a major constraint limiting plant growth on acidic
      soils. Superior Mn tolerance in Stylosanthes spp. has been well documented, but
      its molecular mechanisms remain largely unknown. In this study, superior Mn
      tolerance in Stylosanthes guianensis was confirmed, as reflected by a high Mn
      toxicity threshold. Furthermore, genetic variation of Mn tolerance was evaluated
      using two S. guianensis genotypes, which revealed that the Fine-stem genotype had
      higher Mn tolerance than the TPRC2001-1 genotype, as exhibited through less
      reduction in dry weight under excess Mn, and accompanied by lower internal Mn
      concentrations. Interestingly, Mn-stimulated increases in malate concentrations
      and exudation rates were observed only in the Fine-stem genotype. Proteomic
      analysis of Fine-stem roots revealed that S. guianensis Malate Dehydrogenase1
      (SgMDH1) accumulated in response to Mn toxicity. Western-blot and quantitative
      PCR analyses showed that Mn toxicity resulted in increased SgMDH1 accumulation
      only in Fine-stem roots, but not in TPRC2001-1. The function of SgMDH1-mediated
      malate synthesis was verified through in vitro biochemical analysis of SgMDH1
      activities against oxaloacetate, as well as in vivo increased malate
      concentrations in yeast (Saccharomyces cerevisiae), soybean (Glycine max) hairy
      roots, and Arabidopsis (Arabidopsis thaliana) with SgMDH1 overexpression.
      Furthermore, SgMDH1 overexpression conferred Mn tolerance in Arabidopsis, which
      was accompanied by increased malate exudation and reduced plant Mn
      concentrations, suggesting that secreted malate could alleviate Mn toxicity in
      plants. Taken together, we conclude that the superior Mn tolerance of S.
      guianensis is achieved by coordination of internal and external Mn detoxification
      through malate synthesis and exudation, which is regulated by SgMDH1 at both
      transcription and protein levels. 

PMID- 25378695
TI  - Decreasing electron flux through the cytochrome and/or alternative respiratory
      pathways triggers common and distinct cellular responses dependent on growth
      conditions.
AB  - Diverse signaling pathways are activated by perturbation of mitochondrial
      function under different growth conditions.Mitochondria have emerged as an
      important organelle for sensing and coping with stress in addition to being the
      sites of important metabolic pathways. Here, responses to moderate light and
      drought stress were examined in different Arabidopsis (Arabidopsis thaliana)
      mutant plants lacking a functional alternative oxidase (alternative oxidase1a
      [aox1a]), those with reduced cytochrome electron transport chain capacity (T3/T7
      bacteriophage-type RNA polymerase, mitochondrial, and plastidial [rpoTmp]), and
      double mutants impaired in both pathways (aox1a:rpoTmp). Under conditions
      considered optimal for growth, transcriptomes of aox1a and rpoTmp were distinct.
      Under adverse growth conditions, however, transcriptome changes in aox1a and
      rpoTmp displayed a highly significant overlap and were indicative of a common
      mitochondrial stress response and down-regulation of photosynthesis. This
      suggests that the role of mitochondria to support photosynthesis is provided
      through either the alternative pathway or the cytochrome pathway, and when either
      pathway is inhibited, such as under environmental stress, a common, dramatic, and
      succinct mitochondrial signal is activated to alter energy metabolism in both
      organelles. aox1a:rpoTmp double mutants grown under optimal conditions showed
      dramatic reductions in biomass production compared with aox1a and rpoTmp and a
      transcriptome that was distinct from aox1a or rpoTmp. Transcript data indicating
      activation of mitochondrial biogenesis in aox1a:rpoTmp were supported by a
      proteomic analysis of over 200 proteins. Under optimal conditions, aox1a:rpoTmp
      plants seemed to switch on many of the typical mitochondrial stress regulators.
      Under adverse conditions, aox1a:rpoTmp turned off these responses and displayed a
      biotic stress response. Taken together, these results highlight the diverse
      signaling pathways activated by the perturbation of mitochondrial function under
      different growth conditions. 

PMID- 25378696
TI  - Focus on weed control.

PMID- 25378697
TI  - Angelman syndrome imprinting center encodes a transcriptional promoter.
AB  - Clusters of imprinted genes are often controlled by an imprinting center that is
      necessary for allele-specific gene expression and to reprogram parent-of-origin
      information between generations. An imprinted domain at 15q11-q13 is responsible
      for both Angelman syndrome (AS) and Prader-Willi syndrome (PWS), two clinically
      distinct neurodevelopmental disorders. Angelman syndrome arises from the lack of
      maternal contribution from the locus, whereas Prader-Willi syndrome results from
      the absence of paternally expressed genes. In some rare cases of PWS and AS,
      small deletions may lead to incorrect parent-of-origin allele identity. DNA
      sequences common to these deletions define a bipartite imprinting center for the
      AS-PWS locus. The PWS-smallest region of deletion overlap (SRO) element of the
      imprinting center activates expression of genes from the paternal allele. The AS
      SRO element generates maternal allele identity by epigenetically inactivating the
      PWS-SRO in oocytes so that paternal genes are silenced on the future maternal
      allele. Here we have investigated functional activities of the AS-SRO, the
      element necessary for maternal allele identity. We find that, in humans, the AS
      SRO is an oocyte-specific promoter that generates transcripts that transit the
      PWS-SRO. Similar upstream promoters were detected in bovine oocytes. This result
      is consistent with a model in which imprinting centers become DNA methylated and
      acquire maternal allele identity in oocytes in response to transiting
      transcription. 

PMID- 25378698
TI  - Days to heading 7, a major quantitative locus determining photoperiod sensitivity
      and regional adaptation in rice.
AB  - Success of modern agriculture relies heavily on breeding of crops with maximal
      regional adaptability and yield potentials. A major limiting factor for crop
      cultivation is their flowering time, which is strongly regulated by day length
      (photoperiod) and temperature. Here we report identification and characterization
      of Days to heading 7 (DTH7), a major genetic locus underlying photoperiod
      sensitivity and grain yield in rice. Map-based cloning reveals that DTH7 encodes
      a pseudo-response regulator protein and its expression is regulated by
      photoperiod. We show that in long days DTH7 acts downstream of the photoreceptor
      phytochrome B to repress the expression of Ehd1, an up-regulator of the
      "florigen" genes (Hd3a and RFT1), leading to delayed flowering. Further, we find
      that haplotype combinations of DTH7 with Grain number, plant height, and heading
      date 7 (Ghd7) and DTH8 correlate well with the heading date and grain yield of
      rice under different photoperiod conditions. Our data provide not only a
      macroscopic view of the genetic control of photoperiod sensitivity in rice but
      also a foundation for breeding of rice cultivars better adapted to the target
      environments using rational design. 

PMID- 25378699
TI  - SUMOylation at K340 inhibits tau degradation through deregulating its
      phosphorylation and ubiquitination.
AB  - Intracellular accumulation of the abnormally modified tau is hallmark pathology
      of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not
      fully characterized. Here, we studied the effects of tau SUMOylation on its
      phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation
      induces tau hyperphosphorylation at multiple AD-associated sites, whereas site
      specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous
      inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small
      ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation
      promotes its SUMOylation; the latter in turn inhibits tau degradation with
      reduction of solubility and ubiquitination of tau proteins. Furthermore, the
      enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is
      detected in cerebral cortex of the AD brains, and beta-amyloid exposure of rat
      primary hippocampal neurons induces a dose-dependent SUMOylation of the
      hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally
      stimulates its phosphorylation and inhibits the ubiquitination-mediated tau
      degradation, which provides a new insight into the AD-like tau accumulation. 

PMID- 25378700
TI  - Osteoblast regulation via ligand-activated nuclear trafficking of the oxytocin
      receptor.
AB  - We report that oxytocin (Oxt) receptors (Oxtrs), on stimulation by the ligand
      Oxt, translocate into the nucleus of osteoblasts, implicating this process in the
      action of Oxt on osteoblast maturation. Sequential immunocytochemistry of intact
      cells or isolated nucleoplasts stripped of the outer nuclear membrane showed
      progressive nuclear localization of the Oxtr; this nuclear translocation was
      confirmed by monitoring the movement of Oxtr-EGFP as well as by immunogold
      labeling. Nuclear Oxtr localization was conclusively shown by Western
      immunoblotting and MS of nuclear lysate proteins. We found that the passage of
      Oxtrs into the nucleus was facilitated by successive interactions with beta
      arrestins (Arrbs), the small GTPase Rab5, importin-beta (Kpnb1), and transportin
      1 (Tnpo1). siRNA-mediated knockdown of Arrb1, Arrb2, or Tnpo1 abrogated Oxt
      induced expression of the osteoblast differentiation genes osterix (Sp7), Atf4,
      bone sialoprotein (Ibsp), and osteocalcin (Bglap) without affecting Erk
      phosphorylation. Likewise and again, without affecting pErk, inhibiting Arrb
      recruitment by mutating Ser rich clusters of the nuclear localization signal to
      Ala abolished nuclear import and Oxtr-induced gene expression. These studies
      define a previously unidentified mechanism for Oxtr action on bone and open
      possibilities for direct transcriptional modulation by nuclear G protein-coupled
      receptors. 

PMID- 25378701
TI  - Copper is an endogenous modulator of neural circuit spontaneous activity.
AB  - For reasons that remain insufficiently understood, the brain requires among the
      highest levels of metals in the body for normal function. The traditional
      paradigm for this organ and others is that fluxes of alkali and alkaline earth
      metals are required for signaling, but transition metals are maintained in
      static, tightly bound reservoirs for metabolism and protection against oxidative
      stress. Here we show that copper is an endogenous modulator of spontaneous
      activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3),
      a new fluorescent Cu(+) sensor for one- and two-photon imaging, we show that
      neurons and neural tissue maintain basal stores of loosely bound copper that can
      be attenuated by chelation, which define a labile copper pool. Targeted
      disruption of these labile copper stores by acute chelation or genetic knockdown
      of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal
      properties of spontaneous activity in developing hippocampal and retinal
      circuits. The data identify an essential role for copper neuronal function and
      suggest broader contributions of this transition metal to cell signaling. 

PMID- 25378703
TI  - Sphericity and symmetry breaking in the formation of Frank-Kasper phases from one
      component materials.
AB  - Frank-Kasper phases are tetrahedrally packed structures occurring in numerous
      materials, from elements to intermetallics to self-assembled soft materials. They
      exhibit complex manifolds of Wigner-Seitz cells with many-faceted polyhedra,
      forming an important bridge between the simple close-packed periodic and
      quasiperiodic crystals. The recent discovery of the Frank-Kasper sigma-phase in
      diblock and tetrablock polymers stimulated the experiments reported here on a
      poly(isoprene-b-lactide) diblock copolymer melt. Analysis of small-angle X-ray
      scattering and mechanical spectroscopy exposes an undiscovered competition
      between the tendency to form self-assembled particles with spherical symmetry,
      and the necessity to fill space at uniform density within the framework imposed
      by the lattice. We thus deduce surprising analogies between the symmetry breaking
      at the body-centered cubic phase to sigma-phase transition in diblock copolymers,
      mediated by exchange of mass, and the symmetry breaking in certain metals and
      alloys (such as the elements Mn and U), mediated by exchange of charge. Similar
      connections are made between the role of sphericity in real space for polymer
      systems, and the role of sphericity in reciprocal space for metallic systems such
      as intermetallic compounds and alloys. These findings establish new links between
      disparate materials classes, provide opportunities to improve the understanding
      of complex crystallization by building on synergies between hard and soft matter,
      and, perhaps most significantly, challenge the view that the symmetry breaking
      required to form reduced symmetry structures (possibly even quasiperiodic
      crystals) requires particles with multiple predetermined shapes and/or sizes. 

PMID- 25378702
TI  - Chromatin landscape and circadian dynamics: Spatial and temporal organization of
      clock transcription.
AB  - Circadian rhythms drive the temporal organization of a wide variety of
      physiological and behavioral functions in ~24-h cycles. This control is achieved
      through a complex program of gene expression. In mammals, the molecular clock
      machinery consists of interconnected transcriptional-translational feedback loops
      that ultimately ensure the proper oscillation of thousands of genes in a tissue
      specific manner. To achieve circadian transcriptional control, chromatin
      remodelers serve the clock machinery by providing appropriate oscillations to the
      epigenome. Recent findings have revealed the presence of circadian interactomes,
      nuclear "hubs" of genome topology where coordinately expressed circadian genes
      physically interact in a spatial and temporal-specific manner. Thus, a circadian
      nuclear landscape seems to exist, whose interplay with metabolic pathways and
      clock regulators translates into specific transcriptional programs. Deciphering
      the molecular mechanisms that connect the circadian clock machinery with the
      nuclear landscape will reveal yet unexplored pathways that link cellular
      metabolism to epigenetic control. 

PMID- 25378704
TI  - Forward genetic screens in mice uncover mediators and suppressors of metastatic
      reactivation.
AB  - We have developed a screening platform for the isolation of genetic entities
      involved in metastatic reactivation. Retroviral libraries of cDNAs from fully
      metastatic breast-cancer cells or pooled microRNAs were transduced into breast
      cancer cells that become dormant upon infiltrating the lung. Upon inoculation in
      the tail vein of mice, the cells that had acquired the ability to undergo
      reactivation generated metastatic lesions. Integrated retroviral vectors were
      recovered from these lesions, sequenced, and subjected to a second round of
      validation. By using this strategy, we isolated canonical genes and microRNAs
      that mediate metastatic reactivation in the lung. To identify genes that oppose
      reactivation, we screened an expression library encoding shRNAs, and we
      identified target genes that encode potential enforcers of dormancy. Our
      screening strategy enables the identification and rapid biological validation of
      single genetic entities that are necessary to maintain dormancy or to induce
      reactivation. This technology should facilitate the elucidation of the molecular
      underpinnings of these processes. 

PMID- 25378706
TI  - Field-induced superconducting phase of FeSe in the BCS-BEC cross-over.
AB  - Fermi systems in the cross-over regime between weakly coupled Bardeen-Cooper
      Schrieffer (BCS) and strongly coupled Bose-Einstein-condensate (BEC) limits are
      among the most fascinating objects to study the behavior of an assembly of
      strongly interacting particles. The physics of this cross-over has been of
      considerable interest both in the fields of condensed matter and ultracold atoms.
      One of the most challenging issues in this regime is the effect of large spin
      imbalance on a Fermi system under magnetic fields. Although several exotic
      physical properties have been predicted theoretically, the experimental
      realization of such an unusual superconducting state has not been achieved so
      far. Here we show that pure single crystals of superconducting FeSe offer the
      possibility to enter the previously unexplored realm where the three energies,
      Fermi energy epsilonF, superconducting gap Delta, and Zeeman energy, become
      comparable. Through the superfluid response, transport, thermoelectric response,
      and spectroscopic-imaging scanning tunneling microscopy, we demonstrate that
      epsilonF of FeSe is extremely small, with the ratio Delta/epsilonF ~ 1(~0.3) in
      the electron (hole) band. Moreover, thermal-conductivity measurements give
      evidence of a distinct phase line below the upper critical field, where the
      Zeeman energy becomes comparable to epsilonF and Delta. The observation of this
      field-induced phase provides insights into previously poorly understood aspects
      of the highly spin-polarized Fermi liquid in the BCS-BEC cross-over regime.

PMID- 25378705
TI  - Circular permutation of a synthetic eukaryotic chromosome with the telomerator.
AB  - Chromosome engineering is a major focus in the fields of systems biology,
      genetics, synthetic biology, and the functional analysis of genomes. Here, we
      describe the "telomerator," a new synthetic biology device for use in
      Saccharomyces cerevisiae. The telomerator is designed to inducibly convert
      circular DNA molecules into mitotically stable, linear chromosomes replete with
      functional telomeres in vivo. The telomerator cassette encodes convergent yeast
      telomere seed sequences flanking the I-SceI homing endonuclease recognition site
      in the center of an intron artificially transplanted into the URA3
      selectable/counterselectable auxotrophic marker. We show that inducible
      expression of the homing endonuclease efficiently generates linear molecules,
      identified by using a simple plate-based screening method. To showcase its
      functionality and utility, we use the telomerator to circularly permute a
      synthetic yeast chromosome originally constructed as a circular molecule, synIXR,
      to generate 51 linear variants. Many of the derived linear chromosomes confer
      unexpected phenotypic properties. This finding indicates that the telomerator
      offers a new way to study the effects of gene placement on chromosomes (i.e.,
      telomere proximity). However, that the majority of synIXR linear derivatives
      support viability highlights inherent tolerance of S. cerevisiae to changes in
      gene order and overall chromosome structure. The telomerator serves as an
      important tool to construct artificial linear chromosomes in yeast; the concept
      can be extended to other eukaryotes. 

PMID- 25378707
TI  - Talon noir: paring can eliminate the need for a biopsy.

PMID- 25378708
TI  - A Nth-order linear algorithm for extracting diffuse correlation spectroscopy
      blood flow indices in heterogeneous tissues.
AB  - Conventional semi-infinite analytical solutions of correlation diffusion equation
      may lead to errors when calculating blood flow index (BFI) from diffuse
      correlation spectroscopy (DCS) measurements in tissues with irregular geometries.
      Very recently, we created an algorithm integrating a Nth-order linear model of
      autocorrelation function with the Monte Carlo simulation of photon migrations in
      homogenous tissues with arbitrary geometries for extraction of BFI (i.e., alphaDB
      ). The purpose of this study is to extend the capability of the Nth-order linear
      algorithm for extracting BFI in heterogeneous tissues with arbitrary geometries.
      The previous linear algorithm was modified to extract BFIs in different types of
      tissues simultaneously through utilizing DCS data at multiple source-detector
      separations. We compared the proposed linear algorithm with the semi-infinite
      homogenous solution in a computer model of adult head with heterogeneous tissue
      layers of scalp, skull, cerebrospinal fluid, and brain. To test the capability of
      the linear algorithm for extracting relative changes of cerebral blood flow
      (rCBF) in deep brain, we assigned ten levels of alphaDB in the brain layer with a
      step decrement of 10% while maintaining alphaDB values constant in other layers.
      Simulation results demonstrate the accuracy (errors < 3%) of high-order (N >= 5)
      linear algorithm in extracting BFIs in different tissue layers and rCBF in deep
      brain. By contrast, the semi-infinite homogenous solution resulted in substantial
      errors in rCBF (34.5% <= errors <= 60.2%) and BFIs in different layers. The Nth
      order linear model simplifies data analysis, thus allowing for online data
      processing and displaying. Future study will test this linear algorithm in
      heterogeneous tissues with different levels of blood flow variations and noises.

PMID- 25378709
TI  - Interfacial tension based on-chip extraction of microparticles confined in
      microfluidic Stokes flows.
AB  - Microfluidics involving two immiscible fluids (oil and water) has been
      increasingly used to produce hydrogel microparticles with wide applications.
      However, it is difficult to extract the microparticles out of the microfluidic
      Stokes flows of oil that have a Reynolds number (the ratio of inertia to viscous
      force) much less than one, where the dominant viscous force tends to drive the
      microparticles to move together with the surrounding oil. Here, we present a
      passive method for extracting hydrogel microparticles in microfluidic Stokes flow
      from oil into aqueous extracting solution on-chip by utilizing the intrinsic
      interfacial tension between oil and the microparticles. We further reveal that
      the thickness of an "extended confining layer" of oil next to the interface
      between oil and aqueous extracting solution must be smaller than the radius of
      microparticles for effective extraction. This method uses a simple planar merging
      microchannel design that can be readily fabricated and further integrated into a
      fluidic system to extract microparticles for wide applications.

PMID- 25378710
TI  - A Reexamination of Developmental Changes in Causal Attributions.
AB  - The current study examined young children's use of the presence or absence of
      extrinsic reward to make inferences about the intrinsic motivation of another
      person. Previous research indicates that most kindergartners do not use a
      discounting heuristic, but it was hypothesized that they may have misinterpreted
      the questions asked. Kindergarten, second, and fourth graders were presented
      stories about children who were rewarded or not rewarded for performing various
      activities Two forms of questioning about motivation were compared. When a
      traditional form was used, kindergartners did not show evidence of a discounting
      heuristic. When the questions were adjusted to ask more specifically about
      intrinsic motivation, children at all grade levels appeared to use a discounting
      heuristic. Results are discussed in terms of the parameters of the attributional
      effects, the possible mechanisms responsible for the phenomena, and the
      significance of the findings for other developmental research using self-report
      techniques.

PMID- 25378711
TI  - Children's Conceptions of Friendship: A Multimethod Study of Developmental
      Changes.
AB  - Although previous research has examined the development of children's conceptions
      of friendship, two major limitations currently exist. First, previous
      investigators have relied principally on a single methodological approach-the
      open-ended interview. Second, little is known about children's expectations of
      other peer relationships or how friendship expectations are distinguished from
      them. These two issues were addressed in the present study by administering
      second-, fourth-, and sixth-grade children three measures: (a) an open-ended
      interview, (b) a story-recognition task, and (c) a questionnaire about the
      importance of different characteristics to friendships and acquaintances. In
      general, friendship expectations based on dispositional characteristics increased
      in saliency with age, whereas characteristics referring to overt behaviors
      remained constant. Several substantive differences were found among the three
      measures. Children recognized the importance of different friendship expectations
      before spontaneously reporting them in the interview. Moreover, the recognition
      tasks yielded a more complete set of friendship expectations than the interview
      did. Finally, children of all ages differentiated between expectations for
      friends and acquaintances, but the degree of differentiation increased with age.

PMID- 25378712
TI  - Theoretical and experimental studies of distance dependent response of micro-ring
      resonator-based ultrasonic detectors for photoacoustic microscopy.
AB  - We present in this paper a systematic study of the distance dependent detection
      characteristics of the newly developed micro-ring resonator (MRR)-based
      ultrasonic detector for photoacoustic microscopy (PAM). A simple analytic model
      was first developed to study the steady-state response to the continuous
      ultrasonic waves. While placing the MRR detector at the acoustic far-field
      provides longer working distance and broader field of view, the detection at
      acoustic near-field offers the improved sensitivity and broader bandwidth but at
      the cost of reduction in the field of view. Furthermore, a numerical model was
      developed to analyze the transient response to the photoacoustic-induced
      impulsive waves. Notably, far-field detection exhibits a flat wavefront of its
      response pattern in the time domain while large distortions are clearly visible
      in the case of near-field detection. Finally, both analytic and numerical models
      are validated by experimental studies. This work establishes a theoretical
      framework for quantitatively analyzing the trade-offs between near-field and far
      field detection using MRR detector, creating a guideline for optimizing the PAM
      for various applications in biomedical imaging and diagnostics.

PMID- 25378713
TI  - Web-Based Intervention for Returning Veterans with Symptoms of Posttraumatic
      Stress Disorder and Risky Alcohol Use.
AB  - A substantial number of military personnel who have served in Iraq (Operation
      Iraqi Freedom; OIF) and Afghanistan (Operating Enduring Freedom; OEF) develop
      symptoms of posttraumatic stress disorder (PTSD) in response to their military
      experiences and many of these same individuals will drink in a risky or
      problematic manner following deployment. If left untreated, PTSD symptoms and
      alcohol problems can become chronic and have a significant, negative impact on
      the lives of veterans, their families and communities. Further, OIF and OEF
      service members are often reluctant to seek treatment for mental health symptoms
      or alcohol problems secondary to stigma. In order to reach this population it is
      essential that new strategies and venues for delivering evidence-based care are
      explored. Web-based interventions are uniquely suited to this cohort of veterans
      in that they have the potential to reach a significant number of veterans who
      commonly use the Web and who might not otherwise receive care. This article will
      review the prevalence of PTSD and alcohol problems among OIF and OEF veterans,
      common barriers they experience with accessing care in traditional mental health
      settings, and what is known about the effectiveness of Web-based approaches for
      PTSD and alcohol problems. It also describes the components of a new Web-based
      intervention, developed by the authors, that uses motivational enhancement and
      cognitive-behavioral strategies to intervene with returning veterans who report
      PTSD symptoms and problem drinking. Recommendations for future directions in
      working with returning veterans with PTSD and alcohol problems will be offered.

PMID- 25378714
TI  - Ambivalence in Older Parent-Adult Child Relationships: Mixed Feelings, Mixed
      Measures.
AB  - This research compared direct and indirect measures of ambivalence, 2 commonly
      used strategies for measuring intergenerational ambivalence between older parents
      and their adult children. Directly and indirectly measured ambivalence,
      corresponding to felt and potential manifestations of the construct, were
      contrasted with each other and across generations. Data were derived from 253
      older parent-adult child dyads participating in the Longitudinal Study of
      Generations in 2005. Direct and indirect measures of ambivalence were moderately
      correlated with each other within each generation. Children expressed greater
      indirect ambivalence than their parents but were no different than their mothers
      or fathers in their levels of direct ambivalence. Multivariate regression
      analyses examining the relationship between each type of ambivalence with
      individual and relationship characteristics found differences in associations
      across equations. The results suggest that direct and indirect measures are
      related but represent 2 distinct conceptions of ambivalence. This research
      highlights the challenges in understanding the full complexity of
      intergenerational relations and suggests that both generational perspectives be
      considered in future research.

PMID- 25378715
TI  - Synthesis of Heterotelechelic Polymers for Conjugation of Two Different Proteins.
AB  - In this report we describe a straightforward approach to synthesize polymers with
      end-groups that bind site-specifically to two different proteins. Telechelic
      biotin, maleimide poly(N-isopropylacrylamide) (pNIPAAm) was synthesized for the
      formation of streptavidin (SAv)-bovine serum albumin (BSA) polymer conjugates.
      Reversible addition-fragmentation chain transfer (RAFT) polymerization of NIPAAm
      was conducted in the presence of biotinylated chain transfer agents (CTAs) with
      either ester or amide linkages, and the resultant alpha-biotinylated pNIPAAm were
      formed with low polydispersity indices (PDI <= 1.09). UV-Vis analysis of the
      trithiocarbonate chain-ends indicated 88% or greater retention of the group. A
      maleimide was introduced to the omega chain-end via a radical cross-coupling
      reaction with a functionalized azo-initiator. The polymer structures were
      characterized by 1H NMR spectroscopy and gel permeation chromatography (GPC). The
      resultant biotin-maleimide heterotelechelic polymer was used to form a SAv-BSA
      heterodimer conjugate. Bioconjugate formation was confirmed by gel
      electrophoresis.

PMID- 25378717
TI  - Photo-Mediated Copper(I)-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) "Click"
      Reactions for Forming Polymer Networks as Shape Memory Materials.
AB  - The formation of polymer networks polymerized with the Copper (I) - catalyzed
      azide - alkyne cycloaddition (CuAAC) click reaction is described along with their
      accompanying utilization as shape memory polymers. Due to the click nature of the
      reaction and the synthetic accessibility of azide and alkyne functional-monomers,
      the polymer architecture was readily controlled through monomer design to
      manipulate crosslink density, ability for further functionalization, and the
      glass transition temperature (55 to 120 degrees C). Free strain recovery is used
      to quantify the shape memory properties of a model CuAAC network resulting in
      excellent shape fixity and recovery of 99%. The step growth nature of this
      polymerization results in homogenous network formation with narrow glass
      transitions ranges having half widths of the transition close to 15 degrees C for
      these materials resulting in shape recovery sharpness of 3.9 %/ degrees C in a
      model system comparable to similarly crosslinked chain growth polymers.
      Utilization of the CuAAC reaction to form shape memory materials opens a range of
      possibilities and behaviors that are not readily achieved in other shape memory
      materials such as (meth) acrylates, thiolene, thiol-Michael, and
      poly(caprolactone) based shape memory materials.

PMID- 25378716
TI  - Particles and microfluidics merged: perspectives of highly sensitive diagnostic
      detection.
AB  - There is a growing need for diagnostic technologies that provide laboratories
      with solutions that improve quality, enhance laboratory system productivity, and
      provide accurate detection of a broad range of infectious diseases and cancers.
      Recent advances in micro- and nanoscience and engineering, in particular in the
      areas of particles and microfluidic technologies, have advanced the "lab-on-a
      chip" concept towards the development of a new generation of point-of-care
      diagnostic devices that could significantly enhance test sensitivity and speed.
      In this review, we will discuss many of the recent advances in microfluidics and
      particle technologies with an eye towards merging these two technologies for
      application in medical diagnostics. Although the potential diagnostic
      applications are virtually unlimited, the most important applications are
      foreseen in the areas of biomarker research, cancer diagnosis, and detection of
      infectious microorganisms.

PMID- 25378719
TI  - The need for data in the world's most violent country.

PMID- 25378720
TI  - Sustainable health: the need for new developmental models.

PMID- 25378722
TI  - Taking mental health into the community.
AB  - The Czech Republic's plan to pilot community-based mental health services is a
      welcome development for people with both mild and severe forms of mental illness.
      Petr Tresnak reports. 

PMID- 25378723
TI  - Glimmers of hope on the Ebola front.
AB  - Daniel Bausch has been assisting with patient care during the current Ebola virus
      disease outbreak in western Africa and - as part of a WHO-led international
      collaboration - is exploring the possible use of experimental therapies and
      vaccines. He tells Fiona Fleck why this outbreak is different. 

PMID- 25378724
TI  - Estimation of maternal and child mortality one year after user-fee elimination:
      an impact evaluation and modelling study in Burkina Faso.
AB  - OBJECTIVE: To estimate the impact on maternal and child mortality after
      eliminating user fees for pregnant women and for children less than five years of
      age in Burkina Faso. METHODS: Two health districts in the Sahel region eliminated
      user fees for facility deliveries and curative consultations for children in
      September 2008. To compare health-care coverage before and after this change, we
      used interrupted time series, propensity scores and three independent data
      sources. Coverage changes were assessed for four variables: women giving birth at
      a health facility, and children aged 1 to 59 months receiving oral rehydration
      salts for diarrhoea, antibiotics for pneumonia and artemesinin for malaria. We
      modelled the mortality impact of coverage changes in the Lives Saved Tool using
      several scenarios. FINDINGS: Coverage increased for all variables, however, the
      increase was not statistically significant for antibiotics for pneumonia. For
      estimated mortality impact, the intervention saved approximately 593 (estimate
      range 168-1060) children's lives in both districts during the first year. This
      lowered the estimated under-five mortality rate from 235 deaths per 1000 live
      births in 2008 to 210 (estimate range 189-228) in 2009. If a similar intervention
      were to be introduced nationwide, 14,000 to 19,000 (estimate range 4000-28,000)
      children's lives could be saved annually. Maternal mortality showed a modest
      decrease in all scenarios. CONCLUSION: In this setting, eliminating user fees
      increased use of health services and may have contributed to reduced child
      mortality.

PMID- 25378725
TI  - Health and happiness: cross-sectional household surveys in Finland, Poland and
      Spain.
AB  - OBJECTIVE: To explore the associations between health and how people evaluate and
      experience their lives. METHODS: We analysed data from nationally-representative
      household surveys originally conducted in 2011-2012 in Finland, Poland and Spain.
      These surveys provided information on 10 800 adults, for whom experienced well
      being was measured using the Day Reconstruction Method and evaluative well-being
      was measured with the Cantril Self-Anchoring Striving Scale. Health status was
      assessed by questions in eight domains including mobility and self-care. We used
      multiple linear regression, structural equation models and multiple
      indicators/multiple causes models to explore factors associated with experienced
      and evaluative well-being. FINDINGS: The multiple indicator/multiple causes model
      conducted over the pooled sample showed that respondents with younger age (effect
      size, beta = 0.19), with higher levels of education (beta = -0.12), a history of
      depression (beta = -0.17), poor health status (beta = 0.29) or poor cognitive
      functioning (beta = 0.09) reported worse experienced well-being. Additional
      factors associated with worse evaluative well-being were male sex (beta = -0.03),
      not living with a partner (beta = 0.07), and lower occupational (beta = -0.07) or
      income levels (beta = 0.08). Health status was the factor most strongly
      correlated with both experienced and evaluative well-being, even after
      controlling for a history of depression, age, income and other sociodemographic
      variables. CONCLUSION: Health status is an important correlate of well-being.
      Therefore, strategies to improve population health would also improve people's
      well-being.

PMID- 25378726
TI  - Developing an alcohol policy assessment toolkit: application in the western
      Pacific.
AB  - OBJECTIVE: To demonstrate the development and feasibility of a tool to assess the
      adequacy of national policies aimed at reducing alcohol consumption and related
      problems. METHODS: We developed a quantitative tool - the Toolkit for Evaluating
      Alcohol policy Stringency and Enforcement (TEASE-16) - to assess the level of
      stringency and enforcement of 16 alcohol control policies. TEASE-16 was applied
      to policy data from nine study areas in the western Pacific: Australia, China
      excluding Hong Kong Special Administrative Region (SAR), Hong Kong SAR, Japan,
      Malaysia, New Zealand, the Philippines, Singapore and Viet Nam. Correlation and
      regression analyses were then used to examine the relationship between alcohol
      policy scores and income-adjusted levels of alcohol consumption per capita.
      FINDINGS: Vast differences exist in how alcohol control policies are implemented
      in the western Pacific. Out of a possible 100 points, the nine study areas
      achieved TEASE-16 scores that ranged from 24.1 points for the Philippines to 67.5
      points for Australia. Study areas with high policy scores - indicating relatively
      strong alcohol policy frameworks - had lower alcohol consumption per capita.
      Sensitivity analyses indicated scores and rankings for each study area remained
      relatively stable across different weighting schemes, indicating that TEASE-16
      was robust. CONCLUSION: TEASE-16 could be used by international and national
      regulatory bodies and policy-makers to guide the design, implementation,
      evaluation and refinement of effective policies to reduce alcohol consumption and
      related problems.

PMID- 25378728
TI  - Measles incidence and reporting trends in Germany, 2007-2011.
AB  - OBJECTIVE: We aimed to quantify progress towards measles elimination in Germany
      from 2007 to 2011 and to estimate any potential underreporting over this period.
      METHODS: We determined the annual incidence of notified cases of measles - for
      each year - in northern, western, eastern and southern Germany and across the
      whole country. We then used measles-related health insurance claims to estimate
      the corresponding incidence. FINDINGS: In each year between 2007 and 2011, there
      were 6.9-19.6 (mean: 10.8) notified cases of measles per million population.
      Incidence decreased with age and showed geographical variation, with highest mean
      incidence - 20.3 cases per million - in southern Germany. Over the study period,
      incidence decreased by 10% (incidence rate ratio, IRR: 0.90; 95% confidence
      interval, CI: 0.85-0.95) per year in western Germany but increased by 77% (IRR:
      1.77; 95% CI: 1.62-1.93) per year in eastern Germany. Although the estimated
      incidence of measles based on insurance claims showed similar trends, these
      estimates were 2.0- to 4.8-fold higher than the incidence of notified cases.
      Comparisons between the data sets indicated that the underreporting increased
      with age and was generally less in years when measles incidence was high than in
      low-incidence years. CONCLUSION: Germany is still far from achieving measles
      elimination. There is substantial regional variation in measles epidemiology and,
      therefore, a need for region-specific interventions. Our analysis indicates
      underreporting in the routine surveillance system between 2007 and 2011,
      especially among adults.

PMID- 25378727
TI  - Trends in all-cause mortality during the scale-up of an antiretroviral therapy
      programme: a cross-sectional study in Lusaka, Zambia.
AB  - OBJECTIVE: To follow the trends in all-cause mortality in Lusaka, Zambia, during
      the scale-up of a national programme of antiretroviral therapy (ART). METHODS:
      Between November 2004 and September 2011, we conducted 12 survey rounds as part
      of a cross-sectional study in Lusaka, with independent sampling in each round. In
      each survey, we asked the heads of 3600 households to state the number of deaths
      in their households in the previous 12 months and the number of orphans aged less
      than 16 years in their households and investigated the heads' knowledge,
      attitudes and practices related to human immunodeficiency virus (HIV). FINDINGS:
      The number of deaths we recorded - per 100 person-years - in each survey ranged
      from 0.92 (95% confidence interval, CI: 0.78-1.09) in September 2011, to 1.94
      (95% CI: 1.60-2.35) in March 2007. We found that mortality decreased only
      modestly each year (mortality rate ratio: 0.98; 95% CI: 0.95-1.00; P = 0.093).
      The proportion of households with orphans under the age of 16 years decreased
      from 17% in 2004 to 7% in 2011. The proportions of respondents who had ever been
      tested for HIV, had a comprehensive knowledge of HIV, knew where to obtain free
      ART and reported that a non-pregnant household member was receiving ART gradually
      increased. CONCLUSION: The expansion of ART services in Lusaka was not associated
      with a reduction in all-cause mortality. Coverage, patient adherence and
      retention may all have to be increased if ART is to have a robust and lasting
      impact at population level in Lusaka.

PMID- 25378731
TI  - The case for global investment in rheumatic heart-disease control.

PMID- 25378729
TI  - Medical and nursing students' intentions to work abroad or in rural areas: a
      cross-sectional survey in Asia and Africa.
AB  - OBJECTIVE: To assess medical and nursing students' intentions to migrate abroad
      or practice in rural areas. METHODS: We surveyed 3199 first- and final-year
      medical and nursing students at 16 premier government institutions in Bangladesh,
      Ethiopia, India, Kenya, Malawi, Nepal, the United Republic of Tanzania and
      Zambia. The survey contained questions to identify factors that could predict
      students' intentions to migrate. Primary outcomes were the likelihoods of
      migrating to work abroad or working in rural areas in the country of training
      within five years post-training. We assessed predictors of migration intentions
      using multivariable proportional odds models. FINDINGS: Among respondents, 28%
      (870/3156) expected to migrate abroad, while only 18% (575/3158) anticipated a
      rural career. More nursing than medical students desired professions abroad (odds
      ratio, OR: 1.76; 95% confidence interval, CI: 1.25-2.48). Career desires before
      matriculation correlated with current intentions for international (OR: 4.49; 95%
      CI: 3.21-6.29) and rural (OR: 4.84; 95% CI: 3.52-6.66) careers. Time spent in
      rural areas before matriculation predicted the preference for a rural career (20
      versus 0 years: OR: 1.53, 95% CI: 1.19-1.98) and against work abroad (20 versus 0
      years: OR: 0.69, 95% CI: 0.50-0.96). CONCLUSION: A significant proportion of
      students surveyed still intend to work abroad or in cities after training. These
      intentions could be identified even before matriculation. Admissions standards
      that account for years spent in rural areas could promote greater graduate
      retention in the country of training and in rural areas.

PMID- 25378730
TI  - Catastrophic household expenditure on health in Nepal: a cross-sectional survey.
AB  - OBJECTIVE: To determine the incidence of - and illnesses commonly associated with
      - catastrophic household expenditure on health in Nepal. METHODS: We did a cross
      sectional population-based survey in five municipalities of Kathmandu Valley
      between November 2011 and January 2012. For each household surveyed, out-of
      pocket spending on health in the previous 30 days that exceeded 10% of the
      household's total expenditure over the same period was considered to be
      catastrophic. We estimated the incidence and intensity of catastrophic health
      expenditure. We identified the illnesses most commonly associated with such
      expenditure using a Poisson regression model and assessed the distribution of
      expenditure by economic quintile of households using the concentration index.
      FINDINGS: Overall, 284 of the 1997 households studied in Kathmandu, i.e. 13.8%
      after adjustment by sampling weight, reported catastrophic health expenditure in
      the 30 days before the survey. After adjusting for confounders, this expenditure
      was found to be associated with injuries, particularly those resulting from road
      traffic accidents. Catastrophic expenditure by households in the poorest quintile
      were associated with at least one episode of diabetes, asthma or heart disease.
      CONCLUSION: In an urban area of Nepal, catastrophic household expenditure on
      health was mostly associated with injuries and noncommunicable diseases such as
      diabetes and asthma. Throughout Nepal, interventions for the control and
      management of noncommunicable diseases and the prevention of road traffic
      accidents should be promoted. A phased introduction of health insurance should
      also reduce the incidence of catastrophic household expenditure.

PMID- 25378732
TI  - Economic crisis and increased immigrant mobility: new challenges in managing
      Chagas disease in Europe.

PMID- 25378734
TI  - Climate change and health: recent progress.

PMID- 25378735
TI  - Health for all: a pathway to economic growth in the Association of South-East
      Asian Nations.

PMID- 25378737
TI  - Making WHO recommendations more responsive.
AB  - Recent World Health Organization (WHO) guidelines not only advise countries on
      what treatment to give patients and when, but also how to roll this out in
      countries. Priya Shetty reports. 

PMID- 25378738
TI  - The science behind the sweetness in our diets.
AB  - Jim Mann tells Fiona Fleck what happened when WHO applied a rigorous new method
      of scientific evaluation to its guideline recommending that we keep our intake of
      "free sugars" in food and drink to less than 10% of dietary intake. 

PMID- 25378739
TI  - Age-specific prevalence of hepatitis B virus infection in young pregnant women,
      Hong Kong Special Administrative Region of China.
AB  - OBJECTIVE: To investigate the age-specific prevalence of hepatitis B virus (HBV)
      infection in young pregnant women in Hong Kong Special Administrative Region
      (SAR), China, and to determine whether an increase in prevalence occurs during
      adolescence. METHODS: HBV prevalence was quantified using data from routine
      antenatal screening for hepatitis B surface antigen (HBsAg) in 10 808 women aged
      25 years or younger born in Hong Kong SAR and managed at a single hospital
      between 1998 and 2011. The effect on prevalence of maternal age, parity and birth
      before or after HBV vaccine availability in 1984 was assessed, using Spearman's
      correlation and multiple logistic regression analysis. FINDINGS: Overall, 7.5% of
      women were HBsAg-positive. The prevalence ranged from 2.3% to 8.4% in those aged
      <= 16 and 23 years, respectively. Women born in or after 1984 and those younger
      than 18 years of age were less likely to be HBsAg-positive (odds ratio, OR:
      0.679; 95% confidence interval, CI: 0.578-0.797) and (OR: 0.311; 95% CI: 0.160
      0.604), respectively. For women born before 1984, there was no association
      between HBsAg carriage and being younger than 18 years of age (OR: 0.60; 95% CI:
      0.262-1.370) Logistic regression analysis showed that the prevalence of HBsAg
      carriage was influenced more by the woman being 18 years old or older (adjusted
      OR, aOR: 2.80; 95% CI: 1.46-5.47) than being born before 1984 (aOR: 1.42; 95% CI:
      1.21-1.67). CONCLUSION: Immunity to HBV in young pregnant women who had been
      vaccinated as neonates decreased in late adolescence.

PMID- 25378740
TI  - Asbestos: use, bans and disease burden in Europe.
AB  - OBJECTIVE: To analyse national data on asbestos use and related diseases in the
      European Region of the World Health Organization (WHO). METHODS: For each of the
      53 countries, per capita asbestos use (kg/capita/year) and age-adjusted mortality
      rates (deaths/million persons/year) due to mesothelioma and asbestosis were
      calculated using the databases of the United States Geological Survey and WHO,
      respectively. Countries were further categorized by ban status: early-ban (ban
      adopted by 2000, n = 17), late-ban (ban adopted 2001-2013, n = 17), and no-ban (n
      = 19). FINDINGS: Between 1920-2012, the highest per capita asbestos use was found
      in the no-ban group. After 2000, early-ban and late-ban groups reduced their
      asbestos use levels to less than or equal to 0.1 kg/capita/year, respectively,
      while the no-ban group maintained a very high use at 2.2 kg/capita/year. Between
      1994 and 2010, the European Region registered 106,180 deaths from mesothelioma
      and asbestosis, accounting for 60% of such deaths worldwide. In the early-ban and
      late-ban groups, 16/17 and 15/17 countries, respectively, reported mesothelioma
      data to WHO, while only 6/19 countries in the no-ban group reported such data.
      The age-adjusted mortality rates for mesothelioma for the early-ban, late-ban and
      no-ban groups were 9.4, 3.7 and 3.2 deaths/million persons/year, respectively.
      Asbestosis rates for the groups were 0.8, 0.9 and 1.5 deaths/million
      persons/year, respectively. CONCLUSION: Within the European Region, the early-ban
      countries reported most of the current asbestos-related deaths. However, this
      might shift to the no-ban countries, since the disease burden will likely
      increase in these countries due the heavy use of asbestos.

PMID- 25378741
TI  - Drug resistance of Mycobacterium tuberculosis in Malawi: a cross-sectional
      survey.
AB  - OBJECTIVE: To document the prevalence of multidrug resistance among people newly
      diagnosed with - and those retreated for - tuberculosis in Malawi. METHODS: We
      conducted a nationally representative survey of people with sputum-smear-positive
      tuberculosis between 2010 and 2011. For all consenting participants, we collected
      demographic and clinical data, two sputum samples and tested for human
      immunodeficiency virus (HIV).The samples underwent resistance testing at the
      Central Reference Laboratory in Lilongwe, Malawi. All Mycobacterium tuberculosis
      isolates found to be multidrug-resistant were retested for resistance to first
      line drugs - and tested for resistance to second-line drugs - at a Supranational
      Tuberculosis Reference Laboratory in South Africa. FINDINGS: Overall, M.
      tuberculosis was isolated from 1777 (83.8%) of the 2120 smear-positive
      tuberculosis patients. Multidrug resistance was identified in five (0.4%) of 1196
      isolates from new cases and 28 (4.8%) of 581 isolates from people undergoing
      retreatment. Of the 31 isolates from retreatment cases who had previously failed
      treatment, nine (29.0%) showed multidrug resistance. Although resistance to
      second-line drugs was found, no cases of extensive drug-resistant tuberculosis
      were detected. HIV testing of people from whom M. tuberculosis isolates were
      obtained showed that 577 (48.2%) of people newly diagnosed and 386 (66.4%) of
      people undergoing retreatment were positive. CONCLUSION: The prevalence of
      multidrug resistance among people with smear-positive tuberculosis was low for
      sub-Saharan Africa - probably reflecting the strength of Malawi's tuberculosis
      control programme. The relatively high prevalence of such resistance observed
      among those with previous treatment failure may highlight a need for a change in
      the national policy for retreating this subgroup of people with tuberculosis.

PMID- 25378742
TI  - Systematic review of statistics on causes of deaths in hospitals: strengthening
      the evidence for policy-makers.
AB  - OBJECTIVE: To systematically review the reliability of hospital data on cause of
      death and encourage periodic reviews of these data using a standard method.
      METHODS: We searched Google Scholar, Pubmed and Biblioteca Virtual de la Salud
      for articles in English, Spanish and Portuguese that reported validation studies
      of data on cause of death. We analysed the results of 199 studies that had used
      medical record reviews to validate the cause of death reported on death
      certificates or by the vital registration system. FINDINGS: The screened studies
      had been published between 1983 and 2013 and their results had been reported in
      English (n = 124), Portuguese (n = 25) or Spanish (n = 50). Only 29 of the
      studies met our inclusion criteria. Of these, 13 had examined cause of death
      patterns at the population level - with a view to correcting cause-specific
      mortality fractions - while the other 16 had been undertaken to identify
      discrepancies in the diagnosis for specific diseases before and after medical
      record review. Most of the selected studies reported substantial misdiagnosis of
      causes of death in hospitals. There was wide variation in study methodologies.
      Many studies did not describe the methods used in sufficient detail to be able to
      assess the reproducibility or comparability of their results. CONCLUSION: The
      assumption that causes of death are being accurately reported in hospitals is
      unfounded. To improve the reliability and usefulness of reported causes of death,
      national governments should do periodic medical record reviews to validate the
      quality of their hospital cause of death data, using a standard.

PMID- 25378743
TI  - Improving the estimation of the tuberculosis burden in India.
AB  - Although India is considered to be the country with the greatest tuberculosis
      burden, estimates of the disease's incidence, prevalence and mortality in India
      rely on sparse data with substantial uncertainty. The relevant available data are
      less reliable than those from countries that have recently improved systems for
      case reporting or recently invested in national surveys of tuberculosis
      prevalence. We explored ways to improve the estimation of the tuberculosis burden
      in India. We focused on case notification data - among the most reliable data
      available - and ways to investigate the associated level of underreporting, as
      well as the need for a national tuberculosis prevalence survey. We discuss
      several recent developments - i.e. changes in national policies relating to
      tuberculosis, World Health Organization guidelines for the investigation of the
      disease, and a rapid diagnostic test - that should improve data collection for
      the estimation of the tuberculosis burden in India and elsewhere. We recommend
      the implementation of an inventory study in India to assess the underreporting of
      tuberculosis cases, as well as a national survey of tuberculosis prevalence. A
      national assessment of drug resistance in Indian strains of Mycobacterium
      tuberculosis should also be considered. The results of such studies will be vital
      for the accurate monitoring of tuberculosis control efforts in India and
      globally. 

PMID- 25378744
TI  - The global diffusion of organ transplantation: trends, drivers and policy
      implications.
AB  - Rising incomes, the spread of personal insurance, lifestyle factors adding to the
      burden of illness, ageing populations, globalization and skills transfer within
      the medical community have increased worldwide demand for organ transplantation.
      The Global Observatory on Donation and Transplantation, which was built in
      response to World Health Assembly resolution WHA57.18, has conducted ongoing
      documentation of global transplantation activities since 2007. In this paper, we
      use the Global Observatory's data to describe the current distribution of - and
      trends in - transplantation activities and to evaluate the role of health systems
      factors and macroeconomics in the diffusion of transplantation technology. We
      then consider the implications of our results for health policies relating to
      organ donation and transplantation. Of the World Health Organization's Member
      States, most now engage in organ transplantation and more than a third performed
      deceased donor transplantation in 2011. In general, the Member States that engage
      in organ transplantation have greater access to physician services and greater
      total health spending per capita than the Member States where organ
      transplantation is not performed. The provision of deceased donor transplantation
      was closely associated with high levels of gross national income per capita.
      There are several ways in which governments can support the ethical development
      of organ donation and transplantation programmes. Specifically, they can ensure
      that appropriate legislation, regulation and oversight are in place, and monitor
      donation and transplantation activities, practices and outcomes. Moreover, they
      can allocate resources towards the training of specialist physicians, surgeons
      and transplant coordinators, and implement a professional donor-procurement
      network. 

PMID- 25378745
TI  - Achieving compliance with the International Health Regulations by overseas
      territories of the United Kingdom of Great Britain and Northern Ireland.
AB  - The 2005 International Health Regulations (IHR) came into force for all Member
      States of the World Health Organization (WHO) in June 2007 and the deadline for
      achieving compliance was June 2012. The purpose of the IHR is to prevent, protect
      against, control - and provide a public health response to - international spread
      of disease. The territory of the United Kingdom of Great Britain and Northern
      Ireland and that of several other Member States, such as China, Denmark, France,
      the Netherlands and the United States of America, include overseas territories,
      which cover a total population of approximately 15 million people. Member States
      have a responsibility to ensure that all parts of their territory comply with the
      IHR. Since WHO has not provided specific guidance on compliance in the special
      circumstances of the overseas territories of Member States, compliance by these
      territories is an issue for self-assessment by Member States themselves. To date,
      no reports have been published on the assessment of IHR compliance in countries
      with overseas territories. We describe a gap analysis done in the United Kingdom
      to assess IHR compliance of its overseas territories. The findings and
      conclusions are broadly applicable to other countries with overseas territories
      which may have yet to assess their compliance with the IHR. Such assessments are
      needed to ensure compliance across all parts of a Member States' territory and to
      increase global health security. 

PMID- 25378748
TI  - The 2014 Ebola outbreak: ethical use of unregistered interventions.

PMID- 25378746
TI  - Establishing an early warning alert and response network following the Solomon
      Islands tsunami in 2013.
AB  - PROBLEM: On 6 February 2013, an 8.0 magnitude earthquake generated a tsunami that
      struck the Santa Cruz Islands, Solomon Islands, killing 10 people and displacing
      over 4700. APPROACH: A post-disaster assessment of the risk of epidemic disease
      transmission recommended the implementation of an early warning alert and
      response network (EWARN) to rapidly detect, assess and respond to potential
      outbreaks in the aftermath of the tsunami. LOCAL SETTING: Almost 40% of the Santa
      Cruz Islands' population were displaced by the disaster, and living in cramped
      temporary camps with poor or absent sanitation facilities and insufficient access
      to clean water. There was no early warning disease surveillance system. RELEVANT
      CHANGES: By 25 February, an EWARN was operational in five health facilities that
      served 90% of the displaced population. Eight priority diseases or syndromes were
      reported weekly; unexpected health events were reported immediately. Between 25
      February and 19 May, 1177 target diseases or syndrome cases were reported. Seven
      alerts were investigated. No sustained transmission or epidemics were identified.
      Reporting compliance was 85%. The EWARN was then transitioned to the routine four
      syndrome early warning disease surveillance system. LESSON LEARNT: It was
      necessary to conduct a detailed assessment to evaluate the risk and potential
      impact of serious infectious disease outbreaks, to assess whether and how
      enhanced early warning disease surveillance should be implemented. Local
      capacities and available resources should be considered in planning EWARN
      implementation. An EWARN can be an opportunity to establish or strengthen early
      warning disease surveillance capabilities.

PMID- 25378749
TI  - Towards the world we want.

PMID- 25378751
TI  - China enters the global vaccine market.
AB  - China is gearing up to supply the world with affordable vaccines that fulfil all
      efficacy, safety and quality requirements. Jane Parry reports. 

PMID- 25378752
TI  - Most people can stay fit and healthy into old age.
AB  - Bruno Vellas tells Fiona Fleck why governments must act now to help older people
      stay fit and healthy. 

PMID- 25378754
TI  - Effect of the economic recession on pharmaceutical policy and medicine sales in
      eight European countries.
AB  - OBJECTIVE: To identify pharmaceutical policy changes during the economic
      recession in eight European countries and to determine whether policy measures
      resulted in lower sales of, and less expenditure on, pharmaceuticals. METHODS:
      Information on pharmaceutical policy changes between 2008 and 2011 in eight
      European countries was obtained from publications and pharmaceutical policy
      databases. Data on the volume and value of the quarterly sales of products
      between 2006 and 2011 in the 10 highest-selling therapeutic classes in each
      country were obtained from a pharmaceutical market research database. We compared
      these indicators in economically stable countries; Austria, Estonia and Finland,
      to those in economically less stable countries, Greece, Ireland, Portugal,
      Slovakia and Spain. FINDINGS: Economically stable countries implemented two to
      seven policy changes each, whereas less stable countries implemented 10 to 22
      each. Of the 88 policy changes identified, 33 occurred in 2010 and 40 in 2011.
      They involved changing out-of-pocket payments for patients in 16 cases, price
      mark-up schemes in 13 and price cuts in 11. Sales volumes increased moderately in
      all countries except Greece and Portugal, which experienced slight declines after
      2009. Sales values decreased in both groups of countries, but fell more in less
      stable countries. CONCLUSION: Less economically stable countries implemented more
      pharmaceutical policy changes during the recession than economically stable
      countries. Unexpectedly, pharmaceutical sales volumes increased in almost all
      countries, whereas sales values declined, especially in less stable countries.

PMID- 25378755
TI  - Adverse childhood experiences and associations with health-harming behaviours in
      young adults: surveys in eight eastern European countries.
AB  - OBJECTIVE: To evaluate the association between adverse childhood experiences -
      e.g. abuse, neglect, domestic violence and parental separation, substance use,
      mental illness or incarceration - and the health of young adults in eight eastern
      European countries. METHODS: Between 2010 and 2013, adverse childhood experience
      surveys were undertaken in Albania, Latvia, Lithuania, Montenegro, Romania, the
      Russian Federation, The former Yugoslav Republic of Macedonia and Turkey. There
      were 10,696 respondents - 59.7% female - aged 18-25 years. Multivariate modelling
      was used to investigate the relationships between adverse childhood experiences
      and health-harming behaviours in early adulthood including substance use,
      physical inactivity and attempted suicide. FINDINGS: Over half of the respondents
      reported at least one adverse childhood experience. Having one adverse childhood
      experience increased the probability of having other adverse childhood
      experiences. The number of adverse childhood experiences was positively
      correlated with subsequent reports of health-harming behaviours. Compared with
      those who reported no adverse experiences, respondents who reported at least four
      adverse childhood experiences were at significantly increased risk of many health
      harming behaviours, with odds ratios varying from 1.68 (95% confidence interval,
      CI: 1.32-2.15) - for physical inactivity - to 48.53 (95% CI: 31.98-76.65) - for
      attempted suicide. Modelling indicated that prevention of adverse childhood
      experiences would substantially reduce the occurrence of many health-harming
      behaviours within the study population. CONCLUSION: Our results indicate that
      individuals who do not develop health-harming behaviours are more likely to have
      experienced safe, nurturing childhoods. Evidence-based programmes to improve
      parenting and support child development need large-scale deployment in eastern
      European.

PMID- 25378756
TI  - Hand, foot and mouth disease in China: evaluating an automated system for the
      detection of outbreaks.
AB  - OBJECTIVE: To evaluate the performance of China's infectious disease automated
      alert and response system in the detection of outbreaks of hand, foot and mouth
      (HFM) disease. METHODS: We estimated size, duration and delay in reporting HFM
      disease outbreaks from cases notified between 1 May 2008 and 30 April 2010 and
      between 1 May 2010 and 30 April 2012, before and after automatic alert and
      response included HFM disease. Sensitivity, specificity and timeliness of
      detection of aberrations in the incidence of HFM disease outbreaks were estimated
      by comparing automated detections to observations of public health staff.
      FINDINGS: The alert and response system recorded 106,005 aberrations in the
      incidence of HFM disease between 1 May 2010 and 30 April 2012 - a mean of 5.6
      aberrations per 100 days in each county that reported HFM disease. The response
      system had a sensitivity of 92.7% and a specificity of 95.0%. The mean delay
      between the reporting of the first case of an outbreak and detection of that
      outbreak by the response system was 2.1 days. Between the first and second study
      periods, the mean size of an HFM disease outbreak decreased from 19.4 to 15.8
      cases and the mean interval between the onset and initial reporting of such an
      outbreak to the public health emergency reporting system decreased from 10.0 to
      9.1 days. CONCLUSION: The automated alert and response system shows good
      sensitivity in the detection of HFM disease outbreaks and appears to be
      relatively rapid. Continued use of this system should allow more effective
      prevention and limitation of such outbreaks in China.

PMID- 25378757
TI  - Childhood diarrhoeal deaths in seven low- and middle-income countries.
AB  - OBJECTIVE: To investigate the clinical characteristics of children who died from
      diarrhoea in low- and middle-income countries, such as the duration of diarrhoea,
      comorbid conditions, care-seeking behaviour and oral rehydration therapy use.
      METHODS: The study included verbal autopsy data on children who died from
      diarrhoea between 2000 and 2012 at seven sites in Bangladesh, Ethiopia, Ghana,
      India, Pakistan, Uganda and the United Republic of Tanzania, respectively. Data
      came from demographic surveillance sites, randomized trials and an extended
      Demographic and Health Survey. The type of diarrhoea was classified as acute
      watery, acute bloody or persistent and risk factors were identified. Deaths in
      children aged 1 to 11 months and 1 to 4 years were analysed separately. FINDINGS:
      The proportion of childhood deaths due to diarrhoea varied considerably across
      the seven sites from less than 3% to 30%. Among children aged 1-4 years, acute
      watery diarrhoea accounted for 31-69% of diarrhoeal deaths, acute bloody
      diarrhoea for 12-28%, and persistent diarrhoea for 12-56%. Among infants aged 1
      11 months, persistent diarrhoea accounted for over 30% of diarrhoeal deaths in
      Ethiopia, India, Pakistan, Uganda and the United Republic of Tanzania. At most
      sites, more than 40% of children who died from persistent diarrhoea were
      malnourished. CONCLUSION: Persistent diarrhoea remains an important cause of
      diarrhoeal death in young children in low- and middle-income countries. Research
      is needed on the public health burden of persistent diarrhoea and current
      treatment practices to understand why children are still dying from the
      condition.

PMID- 25378758
TI  - Proposed declassification of disease categories related to sexual orientation in
      the International Statistical Classification of Diseases and Related Health
      Problems (ICD-11).
AB  - The World Health Organization is developing the 11th revision of the
      International Statistical Classification of Diseases and Related Health Problems
      (ICD-11), planned for publication in 2017. The Working Group on the
      Classification of Sexual Disorders and Sexual Health was charged with reviewing
      and making recommendations on disease categories related to sexuality in the
      chapter on mental and behavioural disorders in the 10th revision (ICD-10),
      published in 1990. This chapter includes categories for diagnoses based primarily
      on sexual orientation even though ICD-10 states that sexual orientation alone is
      not a disorder. This article reviews the scientific evidence and clinical
      rationale for continuing to include these categories in the ICD. A review of the
      evidence published since 1990 found little scientific interest in these
      categories. In addition, the Working Group found no evidence that they are
      clinically useful: they neither contribute to health service delivery or
      treatment selection nor provide essential information for public health
      surveillance. Moreover, use of these categories may create unnecessary harm by
      delaying accurate diagnosis and treatment. The Working Group recommends that
      these categories be deleted entirely from ICD-11. Health concerns related to
      sexual orientation can be better addressed using other ICD categories. 

PMID- 25378759
TI  - Mobile clinics for antiretroviral therapy in rural Mozambique.
AB  - PROBLEM: Despite seven years of investment from the President's Emergency Plan
      For AIDS Relief (PEPFAR), the expansion of human immunodeficiency virus (HIV)
      related services continues to challenge Mozambique's health-care infrastructure,
      especially in the country's rural regions. APPROACH: In 2012, as part of a
      national acceleration plan for HIV care and treatment, Namacurra district
      employed a mobile clinic strategy to provide temporary manpower and physical
      space to expand services at four rural peripheral clinics. This paper describes
      the strategy deployed, the uptake of services and the key lessons learnt in the
      first 18 months of implementation. LOCAL SETTING: In 2012, Namacurra's adult
      population was estimated to be 125,425, and of those 15,803 were estimated to be
      HIV infected. Although there is consistent government support of antiretroviral
      therapy (ART) programmes, national coverage remains low, with less than 15% of
      those eligible having received ART by December 2012. RELEVANT CHANGES: Between
      April 2012 and September 2013, Namacurra district enrolled 4832 new patients into
      HIV care and treatment. By using the mobile clinic strategy for ART expansion,
      the district was able to expand provision of ART from two to six (of a desired
      seven) clinics by September 2013. LESSONS LEARNT: Mobile clinic strategies could
      rapidly expand HIV care and treatment in under-funded settings in ways that both
      build local capacity and are sustainable for local health systems. The clinics
      best serve as a transition to improved capacity at fixed-site services.

PMID- 25378760
TI  - Challenges encountered using standard vector control measures for dengue in Boa
      Vista, Brazil.
AB  - PROBLEM: In 2010, dengue virus (DENV) serotype-4 was detected during a dengue
      outbreak in the Amazonian city of Boa Vista. At that time Brazil was already
      endemic for DENV-1, DENV-2 and DENV-3. This was the first time DENV-4 was
      observed in the country after it was initially detected and eliminated in 1981.
      APPROACH: To hinder the spread of DENV-4 throughout Brazil, standard vector
      control measures were intensified. Vector control professionals visited 56 837
      households in 22 out of 31 districts of Boa Vista, to eliminate mosquito-breeding
      sites. Water storage containers were treated with the larvicide diflubenzuron,
      and deltamethrin was sprayed for adult Aedes aegypti mosquitoes. Fifteen days
      later, a second larvae survey and additional deltamethrin applications were
      performed. LOCAL SETTING: In Brazil, dengue vector control is managed at all
      three government levels. Regular surveillance of Aedes aegypti is done four to
      six times a year to strengthen mosquito control activities in areas with high
      vector density. Educational dengue control campaigns in communities are scarce,
      especially between outbreaks. RELEVANT CHANGES: In spite of extensive
      implementation of all standard control actions recommended by the Brazilian
      dengue control programme, only a slight decrease in mosquito density was
      detected. LESSONS LEARNT: There is a need to redesign all levels of dengue
      control. Public consultation and engagement, behaviour change and actions that go
      beyond technical impositions are required. Vector control programme managers need
      to reflect on what constitutes good practices and whether intermittent
      information campaigns are effective measures for dengue prevention and control.

PMID- 25378761
TI  - Sampling at community level by using satellite imagery and geographical analysis.
AB  - PROBLEM: Traditional random sampling at community level requires a list of every
      individual household that can be randomly selected in the study community. The
      longitudinal demographic surveillance systems often used as sampling frames are
      difficult to create in many resource-poor settings. APPROACH: We used Google
      Earth imagery and geographical analysis software to develop a sampling frame.
      Every household structure within the catchment area was digitized and assigned
      coordinates. A random sample was then generated from the list of households.
      LOCAL SETTING: The sampling took place in Lilongwe, Malawi and formed a part of
      an investigation of the intensity of Plasmodium falciparum transmission in a
      multi-site Phase III trial of a candidate malaria vaccine. RELEVANT CHANGES:
      Creation of a complete list of household coordinates within the catchment area
      allowed us to generate a random sample representative of the population. Once the
      coordinates of the households in that sample had been entered into the hand-held
      receivers of a global positioning system device, the households could be
      accurately identified on the ground and approached. LESSONS LEARNT: In the
      development of a geographical sampling frame, the use of Google Earth satellite
      imagery and geographical software appeared to be an efficient alternative to the
      use of a demographic surveillance system. The use of a complete list of household
      coordinates reduced the time needed to locate households in the random sample.
      Our approach to generate a sampling frame is accurate, has utility beyond
      morbidity studies and appears to be a cost-effective option in resource-poor
      settings.

PMID- 25378762
TI  - The Global Vaccine Safety Initiative: enhancing vaccine pharmacovigilance
      capacity at country level.

PMID- 25378763
TI  - Metabolism and upper thermal limits of Apis mellifera carnica and A. m.
      ligustica.
AB  - The Western honeybees Apis mellifera carnica and A. m. ligustica are closely
      related subspecies living in neighbouring regions. Metabolism and the upper
      lethal thermal limits are crucial physiological traits, adapted in the
      evolutionary process to environment and climate conditions. We investigated
      whether samples from these two ecotypes differ in these traits. The standard
      metabolic rate was higher in the A. m. ligustica population only at a high
      temperature (Ta~40  degrees C; dVCO2=12 nl s-1; P<0.05), probably due to a higher
      body temperature (dTthorax=1.5  degrees C; P<0.01). The critical thermal maximum
      of activity and respiration was similar (difference activity CTmax=0.8  degrees
      C, respiratory CTmax=1.1  degrees C). The lethal temperature (LT50, 8h) revealed
      higher tolerance and survival rates of the Ligustica bees (Carnica 50.3  degrees
      C; Ligustica 51.7  degrees C; P<0.02). Results reveal the adaptation of the two
      subspecies to their historic climate conditions, possibly favouring Ligustica in
      a warming environment.

PMID- 25378764
TI  - The Association of Multiple Neighborhood Perceptions with Depression among a
      Highly Impoverished Urban Sample.

PMID- 25378765
TI  - Nonverbal Social Withdrawal in Depression: Evidence from manual and automatic
      analysis.
AB  - The relationship between nonverbal behavior and severity of depression was
      investigated by following depressed participants over the course of treatment and
      video recording a series of clinical interviews. Facial expressions and head pose
      were analyzed from video using manual and automatic systems. Both systems were
      highly consistent for FACS action units (AUs) and showed similar effects for
      change over time in depression severity. When symptom severity was high,
      participants made fewer affiliative facial expressions (AUs 12 and 15) and more
      non-affiliative facial expressions (AU 14). Participants also exhibited
      diminished head motion (i.e., amplitude and velocity) when symptom severity was
      high. These results are consistent with the Social Withdrawal hypothesis: that
      depressed individuals use nonverbal behavior to maintain or increase
      interpersonal distance. As individuals recover, they send more signals indicating
      a willingness to affiliate. The finding that automatic facial expression analysis
      was both consistent with manual coding and revealed the same pattern of findings
      suggests that automatic facial expression analysis may be ready to relieve the
      burden of manual coding in behavioral and clinical science.

PMID- 25378766
TI  - Can serum glypican-3 be a biomarker for effective diagnosis of hepatocellular
      carcinoma? A meta-analysis of the literature.
AB  - OBJECTIVE: This review is to evaluate the diagnostic value of serum GPC3 for
      hepatocellular carcinoma (HCC) due to conflicting results reported. METHODS: NCBI
      PubMed and Embase were comprehensively searched for studies that have used serum
      GPC3 level as a diagnostic index for HCC. The quality of the included studies was
      assessed. Subgroup analyses were conducted to evaluate the sensitivity and
      specificity of GPC3 as a HCC marker. Statistical analysis was performed with the
      software STATA version 12.0. RESULTS: A total of 22 studies were included. The
      qualities of included studies were relatively poor. Among them, 18 studies have
      shown that serum GPC3 is a specific biomarker for HCC, and the pooled sensitivity
      and specificity of these studies were 69 and 93%, respectively. The other 4
      studies have reported conflicting results, which were not caused by races,
      infection status of HBV and HCV, or assay reagents but due to one common
      experimental design of enrolling liver cirrhosis patients as control subjects.
      CONCLUSIONS: This meta-analysis indicates that serum GPC3 is elevated in HCC
      patients compared with healthy individuals, but more studies are needed to
      evaluate its effectiveness to differentially diagnose HCC and liver cirrhosis.

PMID- 25378767
TI  - Demographic Change and Parent-Child Relationships in Adulthood.
AB  - Demographic changes in who becomes a parent, how many children parents have, and
      the marital statuses of parents and children affect the extent to which parents
      and adult children provide for each other later in life. We describe these
      demographic changes and their implications for the help parents and children give
      each other throughout their adult years. The changing demography of US families
      has increased both generations' need for family assistance among those already
      disadvantaged and has exacerbated differences between the socioeconomically
      advantaged and disadvantaged in the availability of kin support. Variations in
      the marital histories of parents and children also contribute to a divergence
      between mother-child and father-child relationships in later life. The churning
      of couple relationships in both generations blurs the boundaries between who is
      in the family and who is not, threatening the effectiveness of the family safety
      net among those who may need it the most.

PMID- 25378768
TI  - Computer Instruction in Handwriting, Spelling, and Composing for Students with
      Specific Learning Disabilities in Grades 4 to 9.
AB  - Effectiveness of iPad computerized writing instruction was evaluated for 4th to
      9th graders (n=35) with diagnosed specific learning disabilities (SLDs) affecting
      writing: dysgraphia (impaired handwriting), dyslexia (impaired spelling), and
      oral and written language learning disability (OWL LD) (impaired syntax
      composing). Each of the 18 two-hour lessons had multiple learning activities
      aimed at improving subword- (handwriting), word- (spelling), and syntax-
      (sentence composing) level language skills by engaging all four language systems
      (listening, speaking, reading, and writing) to create a functional writing
      system. To evaluate treatment effectiveness, normed measures of handwriting,
      spelling, and composing were used with the exception of one non-normed alphabet
      writing task. Results showed that the sample as a whole improved significantly
      from pretest to posttest in three handwriting measures, four spelling measures,
      and both written and oral syntax construction measures. All but oral syntax was
      evaluated with pen and paper tasks, showing that the computer writing instruction
      transferred to better writing with pen and paper. Performance on learning
      activities during instruction correlated with writing outcomes; and individual
      students tended to improve in the impaired skill associated with their diagnosis.
      Thus, although computers are often used in upper elementary school and middle
      school in the United States (US) for accommodations (alternatives to pen and
      paper) for students with persisting SLDs affecting writing, this study shows
      computers can also be used for Tier 3 instruction to improve the writing skills
      of students in grades 4 to 9 with history of persisting writing disabilities.

PMID- 25378769
TI  - Evolving clinical microbiology in the Armed Forces Laboratories for rapid
      detection of antimicrobial resistant bugs and emerging viruses.

PMID- 25378770
TI  - Clinical use of hydroxyethyl starch and serious adverse effects: Need for
      awareness amongst the medical fraternity.

PMID- 25378771
TI  - Usefulness of enzyme immunoassay (EIA) for screening of anti HIV antibodies in
      urinary specimens: A comparative analysis.
AB  - BACKGROUND: Standard HIV testing is done using serum or plasma. FDA approved
      ELISA to screen urine for IgG antibodies to HIV-1 in 1996. It is a simple,
      noninvasive test and is appropriate for developing countries where health care
      personnel may not be professionally trained or where clean needles for drawing
      blood may not always be available. METHODS: 436 individuals with high-risk
      behavior and strong clinical suspicion of HIV infection were screened for IgG
      antibodies to HIV-1 in urine by ELISA. Urine HIV testing was performed by enzyme
      immunoassay, at the ongoing Voluntary Confidential Counseling and Testing Center
      (VCCTC) at a large tertiary care microbiology lab. The individuals enrolled for
      the study had high-risk exposure to the virus and majorities were from a state
      with a high incidence of HIV infection. In all individuals, both serum and urine
      were tested for IgG antibodies to HIV-1. RESULTS: Overall, 135 individuals
      (30.96%) were HIV-positive, of whom 96 (71%) had never previously tested
      positive; 87% of those who tested positive received their results, and most were
      referred for medical care. Sensitivity, specificity and predictive values of HIV
      1 urine ELISA test kit were determined. Sensitivity was found to be 89.6%; 95% CI
      [82.9-94.0], specificity 97.3%; 95% CI [94.6-98.8], positive predictive value
      93.8%; 95% CI [87.8-97.1] and negative predictive value 95.4%; 95% CI [92.3
      97.4]. CONCLUSION: Efficiency, sensitivity, and specificity of the urine-based
      screening for HIV-1 test kits were excellent as compared to the reference test.

PMID- 25378773
TI  - Use of immunization as strategy for outbreak control of varicella zoster in an
      institutional setting.
AB  - BACKGROUND: Outbreaks of varicella gets reported often in India. However,
      outbreak in health care providers living in closed institutional setting and role
      of vaccination as post exposure prophylaxis for control of outbreak has not been
      studied extensively. This paper presents epidemiological investigation and
      control strategy undertaken in such scenario. METHODS: This is an epidemiological
      investigation of chickenpox in nursing students which highlights role of early
      identification and appropriate control strategy to prevent explosive outbreak in
      high risk vulnerable population. Vaccination of all susceptible in addition to
      isolation of cases, quarantine of suspects and proper screening for new cases was
      the major control strategy adopted. RESULTS: The index case was imported and all
      eight cases occurred within the incubation period of the case. Two cases occurred
      in students previously vaccinated for chickenpox. No second or third wave of
      infection occurred showing vaccination as effective tool in outbreak control
      strategy. CONCLUSION: Early identification of cases and vaccination of all
      susceptible contributed to effective control of the outbreak.

PMID- 25378772
TI  - In vitro vancomycin susceptibility amongst methicillin resistant Staphylococcus
      aureus.
AB  - BACKGROUND: Vancomycin is drug of choice for treatment of Methicillin Resistant
      Staphylococcus aureus (MRSA) infections. S. aureus with reduced vancomycin
      susceptibility (SA-RVS) is on rise. Current guidelines of detection of SA-RVS are
      based on MIC (Minimum Inhibitory Concentration) by broth or agar dilution
      methods. Vancomycin MIC by E test (Epsilometer Test) is an alternative. A study
      was undertaken to know the prevalence of SA-RVS and compare vancomycin MIC by
      agar dilution and E test. METHODS: A prospective study was undertaken at tertiary
      care hospital; 232 clinical MRSA isolates were included. Vancomycin MIC was
      undertaken by agar dilution method and E test. RESULTS: All isolates were
      sensitive to Linezolid. Two MRSA isolates had vancomycin MIC >=4 MUg/ml;
      vancomycin MIC50 and MIC90 of MRSA isolates was 0.5 and 0.2 MUg/ml respectively
      by agar dilution method. There was agreement over 93.5% isolates in vancomycin
      susceptibility by agar dilution and E test. E test had sensitivity and positive
      predictive value of 1.0 (CI - 0.34-1.0) and 0.5 (CI - 0.17-0.83) respectively
      compare to agar dilution method. CONCLUSIONS: MRSA isolates continues to be
      susceptible to vancomycin and Linezolid. E test was found equally suitable in
      initial screening for vancomycin susceptibility. Due to geographic variation in
      prevalence, there is need of ongoing surveillance of SA-RVC.

PMID- 25378774
TI  - A study of Hepatitis A and E virus seropositivity profile amongst young healthy
      adults in India.
AB  - BACKGROUND: Various Serosurveys and studies provide ample evidence of differing
      perspectives regarding epidemiology of HAV and HEV in India. This study was
      conducted to assess the seroprevalence of HAV and HEV and its associated factors
      with an aim to provide inputs to planners regarding requirement of HAV vaccine.
      METHODS: A multi-centric cross sectional survey amongst 4175 healthy trainees
      (young adults) was carried out in training centres, selected by multistage random
      sampling, giving equal representation to all regions of India. Sample size was
      calculated by taking prevalence of HAV seropositivity amongst adults as 60% and
      alpha 0.05. RESULTS: Seroprevalence for HAV and HEV was 92.68% (95% CI 91.82,
      93.47) and 17.05% (15.90, 18.26), respectively. Logistic regression showed that
      hand washing without soap, regular close contact with domestic animals,
      consumption of unpasteurized milk and regular consumption of food outside home
      were risk factors for HAV (p < 0.05). For HEV, irregular hand washing,
      consumption of unpasteurized milk and irregular consumption of freshly prepared
      food were risk factors (p < 0.05). CONCLUSION: High level of immunity against HAV
      among the healthy young adults clearly demonstrates that vaccination against HAV
      is not required at present in our country. The large proportion being susceptible
      to HEV points towards the requirement of preventive strategies in the form of
      safe drinking water supply, hygiene, sanitation, increasing awareness and
      behaviour change with respect to personal hygiene especially hand and food
      hygiene.

PMID- 25378775
TI  - Efficacy of contrast enhanced grey scale ultrasound in characterisation of
      hepatic focal lesions: A pilot study.
AB  - BACKGROUND: Contrast enhanced ultrasound (CEUS) has recently gained widespread
      acceptance as an adjunct to conventional grey scale ultrasound. The present pilot
      study was undertaken to evaluate the efficacy of this technique in
      characterisation of hepatic focal lesions. METHODS: Adult patients who had at
      least one focal liver lesion underwent ultrasound evaluation in regular and
      contrast mode before and after intravenous administration of sulphur
      hexafluoride. The diagnoses were confirmed by comparison with a reference
      standard (multidetector CT), response to treatment or pathological correlation.
      RESULTS: The rate of correct diagnosis for unenhanced ultrasound was 54%, CEUS
      was 72% and multidetector CT (MDCT) was 92%. A comparison of unenhanced
      ultrasound versus CEUS using the McNemar test yielded a p value of 0.0704
      (>0.05). However, comparison of CEUS versus MDCT using the McNemar test yielded a
      p value of 0.0265 (<0.05). Additionally, comparison of unenhanced ultrasound
      versus MDCT using the McNemar test yielded a p value of <0.0001. CONCLUSION: CEUS
      increases diagnostic efficacy over unenhanced ultrasound but does not have any
      significant advantages over MDCT. Currently it may be used as a problem solving
      tool in atypical haemangiomas, echogenic focal liver lesions, contrast
      sensitivity and to avoid multiple studies utilising ionising radiation.

PMID- 25378776
TI  - Patient satisfaction with services of the outpatient department.
AB  - BACKGROUND: Patients' satisfaction is a useful measure to provide an indicator of
      quality in healthcare and thus needs to be measured frequently. The aim of the
      study was to analyse and compare the level of satisfaction of patients attending
      the Outpatient Department of a Hospital. METHODS: Study was conducted by using a
      pre-structured questionnaire with 120 samples. Samples were further stratified
      into sub-populations of Officers, Junior Commissioned Officers (JCOs) and Other
      Ranks (ORs) including dependents as study population. RESULTS: JCOs predominantly
      expressed lower satisfaction judgement with several attributes. Overall
      satisfaction judgement with Outpatient Department services were rated lower by
      JCOs (2.56) when compared with Officers and ORs (3.10), the difference being
      statistically significant. CONCLUSION: Statistically significant differences have
      been identified by this study against various study attributes as well as overall
      impression towards OPD services among the study groups, which need to be
      addressed by the hospital leadership to achieve consumer delight.

PMID- 25378777
TI  - Drug-eluting balloon: Initial experience in patients with in-stent restenosis
      (ISR).
AB  - BACKGROUND: In-stent restenosis is the most important limitation of modern
      coronary angioplasty. Drug-eluting stents solve this problem but at the cost of
      late stent thrombosis and longer duration of dual-antiplatelet therapy. Drug
      eluting balloon (DEB) technology is now available and offers an attractive option
      for treatment of restenosis. METHODS: A cohort of 20 patients with in-stent
      restenosis after stenting were treated with a drug-eluting balloon and were
      followed up clinically and angiographically for 6 months. RESULTS AND CONCLUSION:
      Procedural success was achieved in all patients. 6 month clinical follow-up was
      available for all and 6 month angiographic follow up for 17 patients. On 6 month
      follow-up, 5 of the 20 patients had recurrence of angina and 4 patients had
      angiographic restenosis (2 focal, 2 diffuse). The mean Canadian Cardiovascular
      Society angina score improved significantly from 3.1 to 1.1. DEB offers a novel
      method of treatment for patients with in-stent restenosis with a good safety and
      efficacy profile.

PMID- 25378778
TI  - Comparative evaluation of botulinum toxin versus iontophoresis with topical
      aluminium chloride hexahydrate in treatment of palmar hyperhidrosis.
AB  - BACKGROUND: Hyperhidrosis is generalised or focal excessive sweating and carries
      a substantial psychological and social burden. This study compares botulinum
      toxin versus iontophoresis with topical aluminium chloride hexahydrate in palmar
      hyperhidrosis. METHODS: The study included 60 cases of palmar hyperhidrosis
      randomly allocated to 2 groups. One group was given botulinum toxin type A 100
      units per palm and the other group subjected to digital iontophoresis with
      topical application of aluminium chloride hexahydrate lotion for 4 weeks. They
      were assessed 4 weeks later and those without improvement were crossed over to
      the other arm for another 4 weeks. Those with improvement were followed up in the
      same arm for 6 months. RESULTS: Botulinum therapy showed significant improvement
      in the initial (80%) as well as cross over cases (75%) as compared to
      iontophoresis and aluminium chloride (47%) for initial cases and (17%) for cross
      over cases. CONCLUSION: Better improvements were seen with botulinum therapy than
      with iontophoresis and topical therapy. Residual effects of relief lasted on an
      average for 4 months for botulinum toxin whereas it was one month with
      iontophoresis and topical therapy. Advantage with iontophoresis and topical
      therapy was that it was non invasive and did not require regional anaesthesia as
      with botulinum therapy.

PMID- 25378779
TI  - Women empowerment and use of contraception.
AB  - BACKGROUND: Use of contraception is influenced by many processes most by the
      women's empowerment. Women's decision making power and their autonomy within the
      household is the most important factor affecting contraceptive use. This paper
      aims to analyze the relationship between these two indicators of women's
      empowerment and the use of contraception. METHODS: This cross sectional study was
      conducted by personally interviewing 385 currently married women selected by
      systematic sampling on a pretested and validated questionnaire. Two indices,
      women's decision-making power index and women's autonomy index, were constructed
      and association with contraception use analyzed. RESULTS & CONCLUSION: The study
      gives the evidence that decision making power is low in the respondents with
      48.2% (95% CI 43.34, 53.31) of them having low level of power, while 27.6% (95%
      CI 23.24, 32.16) have medium level and 3.6% (95% CI 2.08, 5.88) having high level
      of power. 22.4% (95% CI 18.39, 26.70) of women do not have any autonomy as
      against 43.9% (95% CI 38.99, 48.89) with low level, 25% (95% CI 20.80, 29.44)
      with medium autonomy and 8.7% (95% CI 6.29, 11.98) scoring above 7 (high level of
      autonomy). In the study population it was found that 273 (70.7%, 95% CI 66.2,
      75.28) of the respondents were using contraceptives. Women's autonomy, years of
      marriage and number of children were significant variables.

PMID- 25378780
TI  - Contact Endoscopy of mucosal lesions of oral cavity - Preliminary experience.
AB  - BACKGROUND: Contact Endoscopy is a non invasive tool to visualise alterations in
      cell architecture in vivo. In this study we investigated the diagnostic accuracy
      of Contact Endoscopy in detecting malignancy in oral mucosal lesions. METHODS: 76
      patients with oral mucosal lesions requiring biopsy were included. Contact
      Endoscopy was performed by Otolaryngologist before biopsy and findings recorded.
      The lesion was then biopsied and sent for histopathological examination by
      Pathologist who was blinded to Contact Endoscopy findings. Findings of Contact
      Endoscopy were compared with histopathological findings taking the latter as the
      gold standard. Two biopsies were reported as 'inconclusive' on histopathological
      examination and hence excluded from the final analysis. Data of the remaining 74
      patients is presented here. RESULTS: Clinically lesions were diagnosed as ulcero
      proliferative lesions in 34 patients, Leukoplakia in 19, Erythroplakia in 9,
      Lichen planus in 5 and Submucous fibrosis in 7 patients. Histopathological
      examination revealed presence of malignancy in 97.06% of ulcero-proliferative
      mucosal lesions, 10.53% of leukoplakia and 33.33% of erythroplakia while
      corresponding figures on Contact Endoscopy were 94.12%, 5.26% and 11.11%
      respectively. No malignancy was detected in lichen planus and submucous fibrosis
      by either technique. When compared with histopathological examination, CE showed
      sensitivity of 84.21%, specificity of 94.44% and accuracy of 89.19%. No adverse
      effects on the patients were seen due to the procedure or stain. CONCLUSION:
      Contact Endoscopy may be useful in determining cellular structure in vivo without
      biopsy to detect oral malignancy early. Further studies are suggested.

PMID- 25378781
TI  - Clinical evaluation of overdenture retention using indigenous dental implants.
AB  - BACKGROUND: The continuous resorption of the alveolar ridge after extraction of
      all the teeth can eventually result in a jaw anatomy which offers inadequate
      support for the dentures. This resorption can render the prosthesis inadequate in
      terms of both function and esthetics. METHODS: A study was conducted where 50
      edentulous, denture-wearing patients, of either sex, were given mandibular
      implant overdentures, using their existing denture. The implants used were one
      piece implants with an integrated ball and socket joint for retention. A healing
      time of 3-4 months was given before loading. RESULTS: Implant failure was seen in
      11 cases during the healing phase. A success rate of 78% was seen in this study
      during an observation period of 6 months. This success rate is significantly low
      as compared to global records where a success rate of 87-98% is documented. The
      patients were asked to grade the overdenture as poor, satisfactory, good and
      excellent in categories of masticatory efficiency, speech and overall comfort.
      71.79% patients rated the overall comfort as excellent and the same percentage of
      patients rated the speech as good. CONCLUSION: Implant retained overdentures help
      in improving the masticatory efficiency, speech and overall comfort of the
      patient as compared to conventional dentures.

PMID- 25378782
TI  - Statins: Can we advocate them for primary prevention of heart disease?
AB  - The discovery of cholesterol-lowering agents, namely HMG-CoA reductase inhibitors
      or statins, ushered in a series of large cholesterol reduction trials. The first
      of these studies was the Scandinavian Simvastatin Survival Study (4S) in which
      hypercholesterolemic men with CHD who were treated with simvastatin had a
      reduction in major coronary events of 44% and a reduction in total mortality of
      30%. Many more secondary prevention trials followed to establish unequivocally
      the benefit of cholesterol reduction. Strategies that aim to improve primary
      prevention are important for managing the overall burden of disease. Recently
      therefore, the role of statin in primary prevention is being debated. The JUPITER
      trial and more recently the Cholesterol Treatment Trialists collaborators, proved
      that incidences of first major cardiovascular events in apparently healthy
      individuals were reduced by statins. Statins have also been discussed to be
      having certain pleiotropic effects on other diseases like diabetes, cancer and
      osteoporosis. However, issues of cost effectiveness and adverse effects like
      myositis, and transaminitis still loom large. The medical community needs to
      debate and evolve a possible consensus on the path breaking subject. 

PMID- 25378783
TI  - Outbreak of Influenza (H1N1) amongst children in a residential school.
AB  - BACKGROUND: An outbreak of pandemic Influenza H1N1 occurred from 13 Feb to 20 Feb
      2010 in a residential school at Belgaum, India. METHODS: On report of sudden
      increase in number of students reporting sick with symptoms suggestive of flu
      like illness, an investigation was launched to detect the source of infection and
      to control the spread of infection amongst those not affected. Six random samples
      of throat from the initial cluster were collected and RT-PCR was done to confirm
      the diagnosis. The outbreak in this institution was effectively controlled by
      standard preventive & control measures in the absence of vaccine. RESULT: In a
      school of 335 children, 96 cases of Influenza like illness possibly resulting
      from pH1N1 (2009) were reported with an attack rate of 28.6%. Out of a total of
      96 cases reported, 73 (76%) were hospitalized and 23 treated as outdoor patients.
      Serogroup A of Influenza H1N1 pandemic was identified to be the agent responsible
      for this outbreak as 06 random samples drawn from initial cluster tested positive
      on RT-PCR. A visit to an exhibition in the city was possibly the source of
      exposure amongst the children. CONCLUSION: An outbreak of Influenza H1N1
      infection amongst students in a residential public School was found to be linked
      to a visit to an exhibition following which the secondary transmission led to
      further occurrence of cases.

PMID- 25378784
TI  - Intravenous immunoglobulin in pediatrics: A review.
AB  - There has been a rapid expansion of the use of intravenous immunoglobulin (IVIG)
      for an ever-growing number of conditions. IVIG is used at a 'replacement dose'
      (400-600 mg/kg/month) in antibody deficiencies and is used at a high dose (2
      g/kg) as an 'immunomodulatory' agent in an increasing number of immune and
      inflammatory disorders.(1) The limitations for IVIG are the cost of the
      preparation and the need for intravenous infusions. Due to the cost, shortages
      and growing use of IVIG there have been attempts to develop evidence-based
      guidelines for the use of IVIG in a wide variety of immune disorders in children
      and neonates. This commentary provides the recommendations and recent publication
      regarding the use of IVIG in various conditions in children. 

PMID- 25378785
TI  - Lupus pernio.

PMID- 25378786
TI  - A case of electric cataract.

PMID- 25378787
TI  - Atypical presentation of congenital diaphragmatic hernia.

PMID- 25378788
TI  - Massive ascites and bilateral pleural effusion causing respiratory embarrassment
      in a postnatal case of severe preeclampsia.

PMID- 25378789
TI  - A rare case of hypercholesterolemia in a young girl.

PMID- 25378790
TI  - Letter to the editor.

PMID- 25378791
TI  - Letter to the editor.

PMID- 25378792
TI  - Reply.

PMID- 25378793
TI  - Letter to the editor.

PMID- 25378794
TI  - Reply.

PMID- 25378795
TI  - Reply.

PMID- 25378796
TI  - Decline in CD4 counts in HIV patients.

PMID- 25378797
TI  - Monitoring of malaria, Japanese encephalitis and filariasis vectors: What to be
      concerned?

PMID- 25378798
TI  - Reply.

PMID- 25378799
TI  - Why Intensive Interventions Matter: Longitudinal Studies of Adolescents With
      Reading Disabilities and Poor Reading Comprehension.
AB  - We describe findings from a series of longitudinal studies utilizing a response
      to intervention framework implemented over 3 years with students in Grades 6
      through 8 with reading disabilities and poor reading comprehension. Students were
      identified based on reading comprehension scores in Grade 5 (n = 1,083) and then
      randomized to treatment or comparison conditions. Beginning in sixth grade,
      students assigned to intervention were provided treatment for 1, 2, or 3 years
      based on their response to instruction in each preceding year. Screening
      procedures, progress monitoring tools, tiers of instruction, and findings from
      each year of the study are reported. Additional studies investigating reading and
      behavioral outcomes through multi-level, growth modeling, and studies of the
      cognitive and neural correlates of inadequate response are also reported.

PMID- 25378800
TI  - An onset is an onset: Evidence from abstraction of newly-learned phonotactic
      constraints.
AB  - Phonotactic constraints are language-specific patterns in the sequencing of
      speech sounds. Are these constraints represented at the syllable level (ng cannot
      begin syllables in English) or at the word level (ng cannot begin words)? In a
      continuous recognition-memory task, participants more often falsely recognized
      novel test items that followed than violated the training constraints, whether
      training and test items matched in word structure (one or two syllables) or
      position of restricted consonants (word-edge or word-medial position). E.g.,
      learning that ps are onsets and fs codas, participants generalized from pef (one
      syllable) to putvif (two syllables), and from putvif (word-edge positions) to
      bufpak (word-medial positions). These results suggest that newly-learned
      phonotactic constraints are represented at the syllable level. The syllable is a
      representational unit available and spontaneously used when learning speech-sound
      constraints. In the current experiments, an onset is an onset and a coda a coda,
      regardless of word structure or word position.

PMID- 25378801
TI  - Green Tea Extract-induced Acute Hepatotoxicity in Rats.
AB  - Although green tea is considered to be a healthy beverage, hepatotoxicity
      associated with the consumption of green tea extract has been reported. In the
      present study, we characterized the hepatotoxicity of green tea extract in rats
      and explored the responsible mechanism. Six-week-old IGS rats received a single
      intraperitoneal (ip) injection of 200 mg/kg green tea extract (THEA-FLAN 90S). At
      8, 24, 48 and 72 hrs and 1 and 3 months after exposure, liver damage was assessed
      by using blood-chemistry, histopathology, and immunohistochemistry to detect cell
      death (TUNEL and caspase-3) and proliferative activity (PCNA). Analyses of
      malondialdehyde (MDA) in serum and the liver and of MDA and thymidine glycol (TG)
      by immunohistochemistry, as oxidative stress markers, were performed. Placental
      glutathione S-transferase (GST-P), which is a marker of hepatocarcinogenesis, was
      also immunohistochemically stained. To examine toxicity at older ages, 200 mg/kg
      green tea extract was administered to 18-wk-old female rats. In 6-wk-old rats,
      12% of males and 50% of females died within 72 hrs. In 18-wk-old rats, 88% died
      within 72 hrs. The serum levels of aspartate aminotransferase, alanine
      aminotransferase and/or total bilirubin increased in both males and females.
      Single-cell necrosis with positive signs of TUNEL and caspase-3 was seen in
      perilobular hepatocytes from 8 hrs onward in all lobular areas. PCNA-positive
      hepatocytes increased at 48 hrs. MDA levels in the serum and liver tended to
      increase, and MDA- and TG-positive hepatocytes were seen immunohistochemically.
      GST-P-positive hepatocellular altered foci were detected in one female rat at the
      3-month time point. In conclusion, a single injection of green tea extract
      induced acute and severe hepatotoxicity, which might be associated with lipid
      peroxidation and DNA oxidative stress in hepatocytes. 

PMID- 25378802
TI  - Immunohistochemical characteristics of surfactant proteins a, B, C and d in
      inflammatory and tumorigenic lung lesions of f344 rats.
AB  - Surfactant proteins (SPs), originally known as human lung surfactants, are
      essential to respiratory structure and function. There are 4 subtypes, SP-A, SP
      B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and
      SP-C having physicochemical properties that reduce the surface tension at
      biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C
      and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl)
      nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were
      examined and compared immunohistochemically. Formalin fixed paraffin embedded
      (FFPE) lung samples featuring inflammation were obtained with a rat quartz
      instillation model, and neoplastic lesions, hyperplasias and adenomas, were
      obtained with the rat DHPN-induced lung carcinogenesis model. In the rat quartz
      instillation model, male 10-week old F344 rats were exposed by intratracheal
      instillation (IT) to quartz at a dose of 2 mg/rat suspended in saline (0.2 ml) on
      day 0, and sacrificed on day 28. Lung tumorigenesis in F344 male rats was
      initiated by DHPN in drinking water for 2 weeks, and the animals were then
      sacrificed in week 30. Lung proliferative lesions, hyperplasias and adenomas,
      were observed with DHPN, and inflammation was observed with quartz. The
      expressions of SP-A, SP-B, SP-C and SP-D were examined immunohistochemically. SP
      B and SP-C showed strong expression in lung hyperplasias and adenomas, while SP-A
      and SP-D were observed in mucus or exudates in inflammatory alveoli. These
      results suggest the possibility that SP-B and SP-C are related to lung
      tumorigenesis. 

PMID- 25378803
TI  - Five-sixth Nephrectomy in Female Common Marmosets(Callithrix jacchus) as a
      Chronic Renal Failure Model: -A Longitudinal Course of Serum Biochemical,
      Hematological and Histopathological Changes-.
AB  - To assess the relevance and availability of subtotal nephrectomized common
      marmoset monkeys as a chronic renal failure (CRF) model, we observed for 26 weeks
      the pathophysiological condition of female marmosets subjected to five-sixth
      surgical nephrectomy (5/6Nx) by a two-step surgical method. The 5/6Nx marmosets
      showed a significant increase in serum levels of urea nitrogen, creatinine and
      cystatin-C immediately after 5/6Nx surgery. These renal disorder parameters
      subsequently tended to decrease with the passage of time but remained higher than
      the control levels by the end of the study. Hyperplastic parathyroid glands, a
      high turnover state of osteodystrophy in the femoral bone with higher serum ALP
      activity and anemia with hypocellularity of bone marrow were evident. The 5/6Nx
      marmosets showed a stable CRF condition for a long time and some characteristic
      disorders similar to those observed in CRF patients. These diagnostic aspects
      might be a species-specific anatomical and physiological signature, reflecting
      the nutritional condition. The CRF model using 5/6Nx marmosets might become a
      useful method of evaluating the unique mechanism of CRF development. 

PMID- 25378804
TI  - Intratracheal instillation methods and the distribution of administered material
      in the lung of the rat.
AB  - Intratracheal instillation is widely used for respiratory toxicity tests in
      experimental animals. However, there are wide variations in the techniques used
      for instillation, and it is thus difficult to compare the results obtained using
      different techniques. To examine the effect of instillation methods, we compared
      the distribution of a test substance in the lungs of rats after intratracheal
      instillations under various conditions. Rats received an intratracheal
      instillation of 0.3 mL of india ink suspension under different conditions as
      follows: 3 different angles of body restraint, 0 degrees  (supine horizontal), 45
      degrees  (supine head up) and 90 degrees  (vertical head up); 2 instillation
      speeds, high (40 mL/min) and low (4 mL/min); and 2 different devices, a standard
      bulb-tipped gavage needle and an aerosolizing microsprayer designed for
      intratracheal instillation. One hour after treatment under these various
      conditions, rats were sacrificed, and the local distribution of the suspension in
      the lungs was observed. No animal restrained in the supine head-up or vertical
      head-up position died from the treatment; however, fatalities were observed when
      rats were restrained in the supine horizontal position except under high-speed
      dosing conditions with a microsprayer. Better distribution of the suspension in
      the lungs was observed in the rats restrained in the supine head-up position
      after instillation at high speed when compared with other conditions. These
      results indicated that high-speed instillation to the subject restrained in the
      supine head-up position is an appropriate condition for performing intratracheal
      instillation. 

PMID- 25378806
TI  - Intratubular spermatocytic seminomas in 2 sprague-dawley rats.
AB  - This report describes 2 cases of spontaneous intratubular spermatocytic seminomas
      in Sprague-Dawley rats. These rats were sacrificed at 10 weeks old (case 1) and
      40 weeks old (case 2), respectively. Macroscopically, there were no remarkable
      changes in either case. Microscopically, tumor cells were observed within a
      single seminiferous tubule (case 1) or several seminiferous tubules (case 2). The
      proliferating tumor cells were a tripartite cell population comprising small
      lymphocyte-like, intermediate-sized or large-sized cells, with frequent mitoses,
      arranged in sheets or forming a basal layer around a tubule or tubules.
      Immunohistochemically, the tumor cells were strongly positive for proliferating
      cell nuclear antigen and weakly positive for c-kit, neuron specific enolase and
      VASA. Our cases provide valuable background control information for the
      occurrence of seminoma in rats. 

PMID- 25378805
TI  - Exposure to High Doses of Lipopolysaccharide during Ovalbumin Sensitization
      Prevents the Development of Allergic Th2 Responses to a Dietary Antigen.
AB  - Food allergies are driven by aberrant T helper (Th) 2 cells. Lipopolysaccharide
      (LPS) influences the development of Th2-mediated diseases, but its role in food
      allergy and tolerance remains unclear. To address this issue, we established
      mouse models presenting allergic or tolerant responses to ovalbumin (OVA). Mice
      sensitized with crude OVA developed Th2 responses including acute diarrhea,
      increases in serum OVA-specific IgE, dominant production of serum OVA-specific
      IgG1, increases in Th2-type cytokines and proliferation of mast cells in duodenal
      and colonic tissues. Sensitization of mice with crude OVA and LPS abrogated Th2
      type responses observed in allergic mice. The level of OVA-specific proliferation
      in mesenteric lymph node CD4(+) T cells was comparable in allergic and tolerant
      mice, indicating that the tolerance is not caused by anergy and apoptosis of
      antigen-primed T cells. Expression of Th1- and Th2-type cytokines was suppressed
      in whole spleen cells and/or purified spleen CD4(+) T cells of tolerant mice,
      indicating that the tolerance was not caused by the shift from Th2 to Th1. On the
      other hand, interleukin (IL)-10, a regulatory cytokine produced by regulatory T
      cells, was upregulated in whole spleen cells and purified spleen CD4(+) T cells
      of tolerant mice. Furthermore, spleen CD4(+) T cells from tolerant mice
      suppressed the growth of CD4(+) T cells from DO11.10 mice in co-culture. These
      results indicate that tolerance is induced in allergic mice by simultaneous
      exposure to LPS during sensitization with OVA and that a population of T cells
      producing IL-10 plays an important role in the tolerance induction. 

PMID- 25378807
TI  - Cardiotoxic changes of colchicine intoxication in rats: electrocardiographic,
      histopathological and blood chemical analysis.
AB  - The microtubule inhibitor colchicine is cardiotoxic and is suggested to impair
      impulse formation and conduction. However, little is known about the
      electrocardiographic (ECG) changes induced by colchicine in experimental animals
      and the detailed pathogenesis of its cardiotoxicity. Therefore, we analyzed
      cardiotoxicity in colchicine-treated rats using electrocardiographic,
      histopathological and blood-chemistry approaches. A telemetry device for
      transmitting ECG data was implanted into male Crl:CD(SD) rats, and ECG tracings
      were obtained. At 6 weeks of age, 1.25 mg/kg colchicine was injected
      intravenously once daily for 2 consecutive days, and ECG waveforms and heart rate
      variability were analyzed. Furthermore, 1.25 mg/kg colchicine or vehicle was
      injected for 1 or 2 consecutive days in other rats at 6 weeks of age. One day
      after the final dosing, heart and blood samples were taken for histopathological
      and bloodchemical examination. ECG analysis revealed a prolonged RR interval, QRS
      duration, PR interval and QT interval. Heart rate variability analysis showed an
      increase in high frequency (HF) components as an index of parasympathetic nervous
      activity. In blood chemical examinations, colchicine induced high levels of
      parameters of cardiac injury and low levels and/or variations in Ca, inorganic
      phosphorus, potassium and chloride. Histopathologically, colchicine-treated rats
      showed eosinophilic granular degeneration and cytoplasmic vacuolation of
      ventricular myocardial cells but no remarkable change in the atrioventricular
      node. Not only blood chemical and histopathological changes but also ECG changes
      were induced in colchicine-treated rats, which indicated a decrease in myocardium
      excitability and conductivity, and these changes might be related to increased
      parasympathetic nervous activity and low blood Ca levels. 

PMID- 25378808
TI  - Effects of Repeated Intravenous Administration of Dextrans,Water-soluble
      Macromolecules, in Rats.
AB  - We investigated the influence of repeated intravenous administration of dextrans
      (DEXs) to rats. Seven-week-old Sprague Dawley rats (6 males/group) were given
      intravenously 10% saline solutions of dextrans (DEXs), 40 kDa or 200-300 kDa, at
      a dose level of 5 mL/kg/day for 28 days and they were examined
      histopathologically. Another group (3 males/group) was administered saline in a
      similar manner and served as the control. Histopathological changes indicating
      accumulation of DEXs in the mononuclear phagocyte system (MPS) and the liver were
      noted in the treated groups. The incidence and severity of the findings were
      molecular weight-dependent, except for the lungs. These results are considered
      useful in interpreting data from preclinical studies, in which DEXs or their
      derivatives are administered as test or control substances. 

PMID- 25378809
TI  - Catalytic Enantioselective Allylic Amination of Olefins for the Synthesis of ent
      Sitagliptin.
AB  - The presence of nitrogen atoms in most chiral pharmaceutical drugs has motivated
      the development of numerous strategies for the synthesis of enantioenriched
      amines. Current methods are based on the multi-step transformation of pre
      functionalized allylic electrophiles into chiral allylic amines. The
      enantioselective allylic amination of unactivated olefins represents a more
      direct and attractive strategy. We report the enantioselective synthesis of ent
      sitagliptin via an allylic amination of an unactivated terminal olefin.

PMID- 25378810
TI  - Obstacles to the 'cleanliness of our race': HIV, reproductive risk, stratified
      reproduction, and population quality in Hanoi, Vietnam.
AB  - This paper focuses on the interactions between medical professionals in Hanoi,
      Vietnam and their HIV-positive patients who desire children. Drawing on
      ethnographic research, we argue that despite ongoing state and civil society
      efforts to reduce discrimination against people living with HIV (PLHIV), doctors
      do stigmatize patients who choose to reproduce, even if the patients are found to
      have carefully considered all associated risks. While the effects of the Social
      Evils Campaign linger, the doctors' prejudicial stance towards PLHIV's
      reproductive desires and risks also reflects the messages communicated by the
      more recent governmental campaign on Population Quality. The result of this
      stigmatization is a stratification of reproduction among the Vietnamese citizenry
      whereby PLHIV are considered obstacles to 'the cleanliness of the race'.

PMID- 25378812
TI  - A time of change.

PMID- 25378811
TI  - Elevated OPN, IP-10, and neutrophilia in loop-mediated isothermal amplification
      confirmed tuberculosis patients.
AB  - Tuberculosis (TB) is the second most common cause of death from infectious
      diseases and results in high socioeconomic losses to many countries. Proper
      diagnosis is the first step in TB eradication. To develop a rapid, simple, and
      accurate diagnostic TB test and to characterize the prevalence of Mycobacterium
      tuberculosis (MTB) genotypes and immune profiles of TB patients, a total of 37 TB
      patients and 30 healthy control (HC) from Metro Manila were enrolled. Loop
      mediated isothermal amplification (LAMP) reliably detected MTB infection. Manila
      genotype was identified by spoligotyping method in all TB patients. Osteopontin
      (OPN), interferon-gamma-induced protein 10 kDa (IP-10), and neutrophil counts
      were found to reflect the acute stage of MTB infection. The sensitivity and
      specificity were 94.6% and 93.3%, respectively, for both OPN and IP-10, and they
      were 83.8% and 78.6%, respectively, for neutrophils. The combination of OPN, IP
      10, neutrophil count, IL-6, IL-8, TNF-alpha, MCP-1, platelets, galectin-9, and
      leukocyte count correctly identifies all the HC and 96.3% of TB patients. LAMP
      method may serve as a rapid, supportive method in addition to time-consuming
      culture methods. OPN, IP-10, and neutrophil counts are useful in detecting MTB
      infection and may have utility in monitoring the course of the disease.

PMID- 25378813
TI  - Is it truly outrageous to consider radical prostatectomy for men with metastatic
      prostate cancer?
AB  - Radical prostatectomy is a leading form of treatment for non metastatic prostate
      cancer. It has been shown to improve survival in the long term as well as delay
      or prevent the onset of metastatic disease. However, as the treatment of
      metastatic prostate cancer has evolved in the last few years with the
      introduction of newer agents, the possible role of 'cytoreductive' radical
      prostatectomy is now being explored. Preliminary evidence suggests that radical
      prostatectomy may have a future role in this clinical scenario with a potential
      to improve quality and quantity of life in selected patients with metastatic
      disease. 

PMID- 25378814
TI  - Commenatry on Gautam G. Is it truly outrageous to consider radical prostatectomy
      for men with metastatic prostate cancer? Indian J Urol 2014;30:366-7.

PMID- 25378815
TI  - Painful varicoceles: Role of varicocelectomy.
AB  - The incidence of varicocele in the general population is up to 15%. It is
      estimated that the prevalence of pain with varicoceles is around 2-10%. Till the
      year 2000, only two studies evaluated efficacy of varicocelectomy in painful
      varicoceles with conflicting results. Over the past decade many other studies
      have addressed this issue and reported on the treatment outcome and predictors of
      success. We critically appraised studies published from March 2000 to May 2013
      evaluating surgical management in painful varicoceles to provide an evidence
      based review of effectiveness of varicocelectomy in relieving pain in patients
      with symptomatic painful varicoceles. The association between varicoceles and
      pain is not clearly established. Conservative treatment is warranted as the first
      line of treatment in men with painful clinical varicoceles. In carefully selected
      men with clinically palpable varicoceles and associated characteristic chronic
      dull ache, dragging or throbbing pain who do not respond to conservative therapy,
      varicocelectomy is warranted and is associated with approximately 80% success.
      However, surgical success does not always translate into resolution of pain and
      pain might persist even when no varicoceles are detected postoperatively. 

PMID- 25378816
TI  - Continence outcomes following robotic radical prostatectomy: Our experience from
      150 consecutive patients.
AB  - INTRODUCTION: Urinary continence is an important outcome parameter after robot
      assisted radical prostatectomy (RARP). We evaluated the continence outcomes
      following RARP using a double-layered urethrovesical reconstruction. MATERIALS
      AND METHODS: One hundred fifty consecutive patients undergoing RARP and double
      layered urethrovesical reconstruction were prospectively studied for
      preoperative, intraoperative and post operative parameters. Key points followed
      during surgery were: Minimal dissection of sphincteric complex, preservation of
      puboprostatic ligament, selective ligation of deep venous complex and both
      posterior and anterior reconstruction using the Von Velthoven stitch.
      Intraoperative bladder fill test was done at the end of anastomosis to rule out
      urine leak. Check cystogram was done prior to catheter removal in the outpatient
      department. Patients were subsequently followed at regular intervals regarding
      the status of urinary continence. All patients irrespective of adjuvant therapy
      were included in the analysis. RESULTS: The mean age was 64 years (standard
      deviation +/- 6.88), and mean serum PSA was 20.2 ng/ml. The mean BMI was 25.6
      (SD: +/-3.84). The mean prostate weight was 44.09 gm (range 18-103 gm, SD: +/
      15.59). Median days to catheter removal after surgery was 7 (range 4-14 days)
      days. Cystographically determined urinary leaks were seen in two patients. Urine
      leak was managed by delaying catheter removal for 1 week. Minimum 6 month follow
      up was available in 126 patients. 'No pad' status at 1 week, 1 month, 3 months, 6
      months and 1 year was 15.1%, 54.9%, 78%, 90.5% and 94.1%, respectively.
      CONCLUSION: Excellent continence outcomes are observed in patients undergoing
      double-layered urethrovesical reconstruction.

PMID- 25378817
TI  - Changes in pathologic outcomes and operative trends with robot-assisted
      laparoscopic radical prostatectomy.
AB  - INTRODUCTION: We hypothesized that there is a reverse stage migration, or a shift
      toward operating on higher-risk prostate cancer, in patients undergoing robot
      assisted laparoscopic prostatectomy (RALP). We therefore evaluated the stage of
      disease at the time of surgery for patients with prostate cancer at a large
      tertiary academic medical center. MATERIALS AND METHODS: After institutional
      review board approval, we reviewed all patients that had undergone robotic
      prostatectomy. These patients were separated into three categories: An early era
      of 2005-2008, intermediate era of 2009-2010, and a current era of 2011-2012.
      RESULTS: A total of 3451 patients underwent robotic prostatectomy from 2005 to
      2012. The proportion men with clinical T1 tumors declined from 88.3% in the early
      era to 72.2% in the current era (P < 0.0001). Men with preoperative biopsy
      Gleason 6 disease decreased from the early to the current era (P < 0.0001), while
      men with preoperative biopsy Gleason >= 8 showed the opposite trend, increasing
      from the early to the current era (P = 0.0002). From the early to the current
      era, the proportion of patients with National Comprehensive Cancer Network (NCCN)
      low risk prostate cancer decreased, while those with NCCN intermediate and high
      risk disease increased. The proportion of pathologic T3 disease increased from
      15.5% in the early to 30.6% in the current era (P < 0.0001). On the other hand,
      the proportion of pathologic T2/+ SMS (surgical margin status) decreased from
      6.6% in the early era to 3.1% in the current era (P = 0.0002). CONCLUSIONS: We
      have demonstrated a reverse stage migration in men undergoing robotic
      prostatectomy. Despite the increasing proportion of men with extra-capsular
      disease undergoing RALP, the surgical margin status has remained similar. This
      could reflect both the changing dynamics of the population opting for surgery as
      well as the learning curve of the surgeons.

PMID- 25378818
TI  - Practical approach to screen vesicoureteral reflux after a first urinary tract
      infection.
AB  - INTRODUCTION: Vesicoureteral reflux (VUR) is a common pediatric urologic
      disorder. After the first urinary tract infection (UTI), imaging studies are
      recommended, starting with a renal ultrasound (RUS). Voiding cystourethrography
      (VCUG) and dimercaptosuccinic acid (DMSA) scan are the other main radiologic
      studies used to detect VUR. We evaluated the use of RUS as a screening method for
      VUR in children below 2 years of age, in order to avoid unnecessary VCUG.
      MATERIALS AND METHODS: Medical records and imaging studies of infants (<2 years)
      who had their first UTI in a 6 year period were retrospectively reviewed. We
      evaluated the sensitivity, specificity, and negative predictive values of RUS and
      DMSA for diagnosing VUR. RESULTS: Among 155 children (51% males) with their first
      UTI, 148 RUS were performed, 128 VCUG and 29 DMSA. VUR was detected in 21%
      patients; 14.5% low grade and 6.5% high grade. One hundred and twenty-one
      patients underwent both RUS and VCUG, 101 RUS were normal and 20 abnormal. Of the
      normal RUS 98% had no or low grade VUR. Among those with an abnormality on RUS
      30% had high grade VUR (P < 0.001). CONCLUSIONS: After the first UTI in infants
      (<2 years) RUS is a good screening method for VUR. Among such shildren with a
      normal RUS, we do not recommend VCUG or DMSA. In our opinion, VCUG should be
      performed only in patients with abnormal findings in RUS or in recurrent UTI.

PMID- 25378819
TI  - Efficacy of nifedipine and alfuzosin in the management of distal ureteric stones:
      A randomized, controlled study.
AB  - INTRODUCTION: Stone disease is a significant and world-wide health problem.
      Recently, certain drugs have been used as a supplement to observation alone in an
      effort to improve spontaneous stone expulsion. We evaluated the efficacy of
      nifedipine and alfuzosin in the medical treatment of symptomatic, uncomplicated
      distal ureteral stones. MATERIALS AND METHODS: This was a randomized controlled
      prospective study to determine the efficacy of alfuzosin and nifedipine as an
      adjunctive medical therapy, to increases the stone-expulsion rates in distal
      ureteric calculus of size <=10 mm. Investigators and patients were blinded to the
      randomization scheme. Patients were randomly divided into three equal groups of
      35 patients each. Patients in Group I received tablet nifedipine 30 mg/day, Group
      II received alfuzosin 10 mg/day and Group III was the control group received
      tablet diclofenac sodium. The patient blood pressure, stone position on imaging,
      number of pain attacks, time of stone-expulsion, hospital re-admission and any
      adverse events were assessed. Patients were followed-up weekly and continued
      until the patient was rendered stone free or up to 28 days. Statistical analysis
      was performed and P < 0.05 was considered to be significant. RESULTS: Stone
      expulsion was observed in 60%, 85.7% and 20% patients in Group I, II and III
      respectively. A statistically significant difference was noted in between Groups
      I versus III, Groups II versus III and Groups I versus II (P < 0.0001, P <
      0.0001, and P < 0.0315 respectively). The mean number of pain attacks was 2.91 +/
      1.01 for Group I, 1.8 +/- 0.83 for Group II, and 2.82 +/- 1.12 for Group III,
      which is statistical significant in Groups II versus III, and Groups I versus II
      (P < 0.001 and P < 0.001). Hospital re-admission rate was less in treatment
      groups when compare to control group (P < 0.0001). CONCLUSION: The use of
      alfuzosin and nifedipine as a medical expulsive therapy for distal ureteric
      stones proved to be safe and effective in term of increased stone-expulsion rate,
      reduced pain attacks and decrease hospital re-admissions.

PMID- 25378821
TI  - Current concepts in robotic radical prostatectomy.

PMID- 25378820
TI  - Outcome of tubularized incised plate urethroplasty with spongioplasty alone as
      additional tissue cover: A prospective study.
AB  - INTRODUCTION: Additional cover after neourethra formation to decrease the fistula
      rate, has been described using the dartos, tunica, denuded skin and corpus
      spongiosum. The use of corpus spongiosum alone to cover the neourethra is
      infrequent. The objective of this study was to evaluate the efficacy of
      spongioplasty alone as an intervening layer in the prevention of urethral fistula
      following tubularized incised plate urethroplasty (TIPU). MATERIALS AND METHODS:
      A prospective study was performed including 113 primary hypospadias cases
      undergoing TIPU with spongioplasty from June 2010 to March 2012. Correction of
      chordee was carried out by penile degloving alone in 5, mobilization of urethral
      plate with spongiosum in 22 and combination of both in 45 cases. Intra
      operatively, spongiosum was taken to be poorly developed if it was thin and
      fibrous, moderate if good spongiosal tissue with good vascularization and well
      developed if healthy robust spongiosum, which became bulkier than native
      spongiosum after tubularisation. Spongioplasty was done in a single layer after
      mobilization of spongiosum, starting just proximal to the native meatus and into
      the glans distally. RESULTS: The mean age of the patients was 11.53 years. The
      type of hypospadias was distal, mid and proximal in 81, 12 and 20 cases
      respectively. Spongiosum was poorly developed in 13, moderate in 53 and well
      developed in 47 cases. The mean hospital stay was 8-10 days and follow-up ranged
      from 6 months to 2 years. Urethral fistula was seen in six patients (11.3%) with
      moderate spongiosum (distal 1, mid 1 and proximal 4), and three (23.03%) with
      poorly developed spongiosum (one each in distal, mid and proximal) with an
      overall 7.96% fistula rate. None of the patients with well-developed spongiosum
      developed a fistula. Poorer spongiosum correlated with a greater number of
      complications (P = 0.011). Five out of thirteen cases with poor spongiosum
      (38.46%) had proximal hypospadias, i.e. more proximal was the hypospadias, poorer
      was the development of the spongiosum (P = 0.05). Meatal stenosis was seen in two
      patients (1.76%) with proximal hypospadias, one with moderate and the other with
      poorly developed spongiosum. More proximal was the hypospadias, greater were the
      number of complications (P = 0.0019). CONCLUSION: TIPU with spongioplasty
      reconstructs a near normal urethra with low complications. Better developed and
      thicker spongiosum results in lower incidence of fistula and meatal stenosis.
      More proximal hypospadias is associated with poorer spongiosum. We recommend
      spongioplasty to be incorporated as an essential step in all patients undergoing
      tubularized incised-plate repair for hypospadias.

PMID- 25378822
TI  - Newer concepts in neural anatomy and neurovascular preservation in robotic
      radical prostatectomy.
AB  - With more than 60% of radical prostatectomies being performed robotically,
      robotic-assisted laparoscopic prostatectomy (RALP) has largely replaced the open
      and laparoscopic approaches and has become the standard of care surgical
      treatment option for localized prostate cancer in the United States.
      Accomplishing negative surgical margins while preserving functional outcomes of
      sexual function and continence play a significant role in determining the success
      of surgical intervention, particularly since the advent of nerve-sparing (NS)
      robotic prostatectomy. Recent evidence suggests that NS surgery improves
      continence in addition to sexual function. In this review, we describe the
      neuroanatomical concepts and recent developments in the NS technique of RALP with
      a view to improving the "trifecta" outcomes. 

PMID- 25378823
TI  - Role of robot-assisted radical prostatectomy in the management of high-risk
      prostate cancer.
AB  - We aimed to evaluate the role of robot-assisted radical prostatectomy (RARP) in
      the management of high-risk prostate cancer (PCa), with a focus on oncological,
      functional and perioperative outcomes. Further, we also aimed to briefly describe
      our novel modification to conventional RARP that allows immediate organ retrieval
      and examination for intra-operative surgical margin assessment. A literature
      search of PubMed was performed for articles on the management of high-risk PCa.
      Papers written in English and concerning clinical outcomes following RARP for
      locally advanced and high-risk PCa were selected. Outcomes data from our own
      center were also included. A total of 10 contemporary series were evaluated.
      Biopsy Gleason score >= 8 was the most common cause for classification of
      patients into the high-risk PCa group. Biochemical failure rate, in the few
      series that looked at long-term follow-up, varied from 9% to 26% at 1 year. The
      positive surgical margin rate varied from 12% to 53.3%. Urinary continence rates
      varied from 78% to 92% at 1 year. The overall complication rates varied from 2.4%
      to 30%, with anastomotic leak and lymphocele being the most common complications.
      Long-term data on oncological control following RARP in high-risk patients is
      lacking. Short-term oncological outcomes and functional outcomes are equivalent
      to open radical prostatectomy (RP). Safety outcomes are better in patients
      undergoing RARP when compared with open RP. Improved tools for predicting the
      presence of organ-confined disease (OCD) are available. High-risk patients with
      OCD would be ideal candidates for RARP and would benefit most from surgery alone.

PMID- 25378824
TI  - Handling difficult anastomosis. Tips and tricks in obese patients and narrow
      pelvis.
AB  - Vesico-urethral anastomosis (VUA) is a technically challenging step in robotic
      assisted laparoscopic prostatectomy (RALP) in obese individuals. We describe
      technical modifications to facilitate VUA encountered in obese individuals and in
      patients with a narrow pelvis. A Pubmed literature search was performed between
      2000 and 2012 to review all articles related to RALP, obesity and VUA for
      evaluation of technique, complications and outcomes of VUA in obese individuals.
      In addition to the technical modifications described in the literature, we
      describe our own experience to encounter the technical challenges induced by
      obesity and narrow pelvis. In obese patients, technical modifications like use of
      air seal trocar technology, steep Trendlenburg positioning, bariatric trocars,
      alterations in trocar placement, barbed suture and use of modified posterior
      reconstruction facilitate VUA in robotic-assisted radical prostatectomy. The
      dexterity of the robot and the technical modifications help to perform the VUA in
      challenging patients with lesser difficulty. The experience of the surgeon is a
      critical factor in outcomes in these technically challenging patients, and obese
      individuals are best avoided during the initial phase of the learning curve. 

PMID- 25378825
TI  - Significance and management of positive surgical margins at the time of radical
      prostatectomy.
AB  - Positive surgical margins (PSM) at the time of radical prostatectomy (RP) result
      in an increased risk of biochemical recurrence (BCR) and secondary treatment. We
      review current literature with a focus on stratifying the characteristics of the
      PSM that may define its significance, the impact of modern imaging and surgical
      approaches in avoidance of PSM, and management strategies when PSM do occur. We
      performed a review of the available literature to identify factors associated
      with PSM and their management. PSM have been repeatedly demonstrated to be
      associated with an increased risk of BCR following RP. The specific
      characteristics (size, number, location, Gleason score at the margin) of the PSM
      may influence the risk of recurrence. Novel imaging and surgical approaches are
      being investigated and may allow for reductions of PSM in the future. The use of
      adjuvant treatment for a PSM remains controversial and should be decided on an
      individual basis after a discussion about the risks and benefits. The goal of RP
      is complete resection of the tumor. PSM are associated with increased risk of BCR
      and secondary treatments. Of the risk factors associated with BCR after RP, a PSM
      is directly influenced by surgical technique. 

PMID- 25378826
TI  - Salvage robotic radical prostatectomy.
AB  - Failure of non-surgical primary treatment for localized prostate cancer is a
      common occurrence, with rates of disease recurrence ranging from 20% to 60%. In a
      large proportion of patients, disease recurrence is clinically localized and
      therefore potentially curable. Unfortunately, due to the complex and potentially
      morbid nature of salvage treatment, radical salvage surgery is uncommonly
      performed. In an attempt to decrease the morbidity of salvage therapy without
      sacrificing oncologic efficacy, a number of experienced centers have utilized
      robotic assistance to perform minimally invasive salvage radical prostatectomy.
      Herein, we critically evaluate the existing literature on salvage robotic radical
      prostatectomy with a focus on patient selection, perioperative complications and
      functional and early oncologic outcomes. These results are compared with
      contemporary and historical open salvage radical prostatectomy series and
      supplemented with insights we have gained from our experience with salvage
      robotic radical prostatectomy. The body of evidence by which conclusions
      regarding the efficacy and safety of robotic salvage radical prostatectomy can be
      drawn comprises fewer than 200 patients with limited follow-up. Preliminary
      results are promising and some outcomes have been favorable when compared with
      contemporary open salvage prostatectomy series. Advantages of the robotic
      platform in the performance of salvage radical prostatectomy include decreased
      blood loss, short length of stay and improved visualization. Greater experience
      is required to confirm the long-term oncologic efficacy and functional outcomes
      as well as the generalizability of results achieved at experienced centers. 

PMID- 25378828
TI  - Ureteritis cystica: A rare entity in children.
AB  - Ureteritis cystica (UC) is a benign condition. Although it can often be diagnosed
      with imaging techniques, we report a case of a child for whom we planned
      nephrectomy and ureteral augmentation cystoplasty, but abandoned the cystoplasty
      due to extensive UC in the ureter. 

PMID- 25378827
TI  - Erectile dysfunction in robotic radical prostatectomy: Outcomes and management.
AB  - Robot-assisted laparoscopic prostatectomy (RALP) has emerged as the most common
      treatment for localized prostate cancer. With improved surgical precision, RALP
      has produced hope of improved potency rates, especially with the advent of nerve
      sparing and other modified techniques. However, erectile dysfunction (ED) remains
      a significant problem for many men regardless of surgical technique. To identify
      the functional outcomes of robotic versus open and laparoscopic techniques, new
      robotic surgical techniques and current treatment options of ED following RALP. A
      Medline search was performed in March 2014 to identify studies comparing RALP
      with open retropubic radical prostatectomy (RRP) and laparoscopic radical
      prostatectomy, modified RALP techniques and treatment options and management for
      ED following radical prostatectomy. RALP demonstrates adequate potency rates
      without compromising oncologic benefit, with observed benefit for potency rates
      compared with RRP. Additionally, specific surgical technical modifications appear
      to provide benefit over traditional RALP. Phosphodiesterase-5 inhibitors (PDE5I)
      demonstrate benefit for ED treatment compared with placebo. However, long-term
      benefit is often lost after use. Other therapies have been less extensively
      studied. Additionally, correct patient identification is important for greatest
      clinical benefit. RALP appears to provide beneficial potency rates compared with
      RRP; however, these effects are most pronounced at high-volume centers with
      experienced surgeons. No optimal rehabilitation program with PDE5Is has been
      identified based on current data. Additionally, vacuum erection devices,
      intracavernosal injections and other techniques have not been well validated for
      post RALP ED treatment. 

PMID- 25378829
TI  - Small bowel intussusception due to metastatic bladder carcinoma.
AB  - The common sites of metastasis from a urinary bladder carcinoma include lymph
      nodes, bones, lung, liver, and peritoneum. Only a few cases of small bowel
      metastasis from urinary bladder malignancy have been reported in the English
      literature. Only one of these cases presented with bowel intussusception. We
      report a case of an adult small bowel intussusception due to metastasis from a
      urinary bladder carcinoma which is extremely rare as small bowel metastasis occur
      mostly from breast, lungs or melanomas. 

PMID- 25378830
TI  - Arteriovenous malformation causing obstructive uropathy: A different dimension to
      ovarian vein syndrome.
AB  - Ovarian vein syndrome is defined as obstructive uropathy caused by dilated
      ovarian vein with or without thrombosis. This is seen in the puerperal period as
      an acute condition with abdominal pain and fever and in multipara women with
      chronic recurrent abdominal pain. We report an ovarian vein syndrome caused by a
      true vascular anomaly in an 8-year-old child. Laparoscopic ureterolysis was
      performed with ligation of the arteriovenous malformation during the first
      operation. As ureterolysis was not effective, the patient was reoperated and
      ureteroureterostomy was performed after 3 months, which emphasizes the importance
      of removing the diseased segment even if it looks normal. 

PMID- 25378831
TI  - Massive left hemothorax following laparoscopic pyeloplasty.
AB  - Laparoscopic pyeloplasty is viable standard minimally invasive alternative to
      open pyeloplasty for the treatment of ureteropelvic junction obstruction.
      Intrathoracic bleeding is an extremely rare complication after laparoscopic
      urological surgery, but it should be suspected and promptly diagnosed in case of
      worsening hemodynamic status and respiratory parameters during the intra or post
      operative course. We report a case of hemothorax complicating an otherwise
      uneventful LP in an 18-year-old girl. 

PMID- 25378832
TI  - Spontaneous perinephric hemorrhage (Wunderlich syndrome) secondary to
      polyarteritis nodosa: Computed tomography and angiographic findings.
AB  - We report the case of a young man who presented with spontaneous left perinephric
      hematoma and per-rectal bleeding. Evaluation revealed renal and superior
      mesenteric arterial aneurysms secondary to polyarteritis nodosa (PAN). Computed
      tomography and angiographic findings are presented. The aetiology of spontaneous
      perinephric hemorrhage along with relevant features of PAN are discussed. 

PMID- 25378833
TI  - "The creeping tumor:" An unusual presentation of upper urinary tract malignancy.
AB  - Upper urinary tract urothelial malignancy accounts for 5-10% of urothelial
      carcinomas. Synchronous bladder carcinoma occurs in 2-4% of patients with upper
      urinary tract tumors. Urothelial malignancy involving the entire upper urinary
      tract is an extremely rare entity. Most upper urinary tract malignancies are
      transitional cell carcinomas (TCC), of which the sarcomatoid variant is very
      rare. These tumors pose a challenge to the radiologist. We herein report a case
      of TCC involving the entire collecting system of the left kidney, extending down
      along the ureter and projecting as a mass in the bladder. 

PMID- 25378834
TI  - Re: Parikh GP, Sonde SR, Kadam P. Venous air embolism: A complication during
      percutaneous nephrolithotomy. Indian J Urol 2014;30:348-9.

PMID- 25378835
TI  - Re: Sabharwal S, Macaden AR, Abrol N, Mukha RP, Kekre NS. A novel computer based
      stent registry to prevent retained stents: Will patient directed automated short
      message service and letter generator help? Indian J Urol 2014;30:150-2.

PMID- 25378836
TI  - Palliation in metastatic non-small cell lung cancer: Early integration with
      standard oncological care is the key.

PMID- 25378837
TI  - Laying the ground for research of interstitial lung disease in our country: ILD
      India registry.

PMID- 25378838
TI  - Utility of FDG-PET-CT scanning in assessing the extent of disease activity and
      response to treatment in sarcoidosis.
AB  - BACKGROUND: Radionuclide imaging modalities have increasingly been evaluated in
      the assessment of organ involvement in sarcoidosis. Fluoro-deoxyglucose positron
      emission tomography-computed tomography (FDG-PET-CT) scanning has received
      increasing attention in the recent years. The aim of our study was to evaluate
      the utility of FDG-PET-CT in determining the extent of organ involvement and
      disease activity in patients of sarcoidosis and to assess its utility in the
      evaluation of response to therapy. The secondary objective was to compare the
      agreement between clinical, radiological (HRCT) and metabolic indices (FDG-PET
      CT) of disease activity. MATERIALS AND METHODS: This was a prospective
      observational study conducted between March 2007 and December 2008 at a tertiary
      care referral center in north India. Twenty-five symptomatic and
      histopathologically proven cases of sarcoidosis underwent FDG-PET-CT scanning at
      baseline and a follow-up scan in 21 patients at 6-9 months post-treatment with
      glucocorticoids. RESULTS: FDG-PET-CT scan detected metabolic disease activity in
      24 of the 25 patients with clinically active sarcoidosis. It also demonstrated
      many clinically inapparent sites of disease activity. Complete or partial
      metabolic response was seen in 17 of the 21 patients in whom a follow-up scan was
      available. Substantial degree of agreement was found between the metabolic
      response and the radiological response, whereas moderate agreement was found
      between clinical and metabolic responses. CONCLUSIONS: FDG-PET-CT scanning is a
      useful imaging modality to assess disease activity, extent of disease involvement
      and response to treatment in clinically active sarcoidosis. There is substantial
      agreement between the HRCT and metabolic parameters of disease activity. Further,
      large sample size studies are proposed in order to identify the subset of
      patients who are likely to benefit the most from this sensitive modality of
      imaging, especially in developing countries where the cost of the procedure is an
      important concern.

PMID- 25378839
TI  - Utility of noninvasive ventilation in high-risk patients during endoscopic
      retrograde cholangiopancreatography.
AB  - BACKGROUND: There is little evidence on noninvasive ventilation (NIV) preventing
      respiratory complications in high-risk patients undergoing endoscopy procedures.
      OBJECTIVES: The objective of this study is to demonstrate that the application of
      NIV through a nasal interface can prevent the appearance of ventilatory
      alterations during endoscopic retrograde cholangiopancreatography (ERCP) in
      patients with risk factors associated with the development of hypoventilation.
      PATIENTS AND METHODS: A non-randomized interventional study was performed on 37
      consecutive high-risk patients undergoing ERCP. During the procedure, 21 patients
      received oxygen by nasal cannula (3 L/minute) and sixteen received NIV through a
      nasal mask. Arterial blood gas analyses were conducted before and immediately
      after the ERCP. An Acute Physiology and Chronic Health Evaluation (APACHE) score
      pre-ERCP was recorded. The complications during the procedure were recorded.
      RESULTS: The groups with and without NIV were comparable. A post-ERCP pH of <7.35
      was found in eight patients, who did not receive ventilatory support (38.1%)
      compared to zero patients in the NIV group (P = 0.006). A post-ERCP pCO2 >45 mmHg
      was found in one case (6.3%) in the NIV-group and in nine cases in the nasal
      cannula group (42.9%; P = 0.01). The median pCO2 post-ERCP was lower (36.5 +/-
      6.2 vs. 44.5 +/- 6.8 mmHg) (P = 0.001) and median pH post-ERCP was higher (7.41
      +/- 0.4 vs. 7.34 +/- 0.5) (P = 0.001) in patients treated with NIV. In the
      multivariate analysis, after adjusting for gender, the APACHE score, pH and pCO2
      pre-ERCP, age, propofol doses, and procedure duration, the following differences
      were maintained (pCO2 difference = 5.54, 95% Confidence Interval (CI) =2.3 - 8.7,
      pH difference = 0.047, and 95% CI = 0.013 - 0.081). Among the 37 procedures, four
      complications occurred: One in the NIV group and three in the nasal cannula
      group. None of them was related to NIV. CONCLUSIONS: Our preliminary results
      demonstrate that in high-risk patients undergoing ERCP, hypercapnia and
      respiratory acidosis are frequent. NIV prevents the appearance of these
      complications.

PMID- 25378840
TI  - Multidrug-resistant-tuberculosis treatment in the Indian private sector: Results
      from a tertiary referral private hospital in Mumbai.
AB  - BACKGROUND: There is very limited data on the experience and outcome of multidrug
      resistant tuberculosis (MDR-TB) patients treated privately out of the DOTS plus
      program. Goal of this study is to provide characteristics and treatment outcomes
      of a prospective cohort of MDR-TB patients managed at a private tertiary referral
      institute. MATERIALS AND METHODS: A prospective analysis of a cohort of MDR-TB
      patients treated in a tertiary private hospital, with the back-up of a Level 2
      mycobacterial laboratory, which has recently received recognition by the Revised
      National Tuberculosis Control Program (RNTCP) for second-line drug susceptibility
      (DST). All patients received an individualized MDR regimen on an ambulatory
      basis. RESULTS: Our 68% success rates are respectable and show that given the
      right laboratory backing, MDR-TB can be managed successfully in selected private
      practice settings.

PMID- 25378841
TI  - Correlation of exhaled nitric oxide, nasal nitric oxide and atopic status: A
      cross-sectional study in bronchial asthma and allergic rhinitis.
AB  - OBJECTIVE: Exhaled nitric oxide (FENO) and nasal nitric oxide (n NO) measurement
      is an area of ongoing research in the study of airway inflammation. The atopic
      status is known to influence the levels of FENO and n NO. This study was
      undertaken to study the relationship between nitric oxide measurements in
      bronchial asthma and allergic rhinitis along with their correlation with atopic
      profile of Indian population. MATERIALS AND METHODS: Ninety subjects were
      recruited for the study comprising of 25 each of bronchial asthma (BA), allergic
      rhinitis (AR), bronchial asthma with allergic rhinitis (BA-AR) and 15 healthy
      controls. These were assessed for atopy and exhaled breath analysis of nitric
      oxide. The measurements of FENO and n NO levels were done using NIOX
      chemiluminescence analyzer. Atopy was assessed by skin prick testing (SPT)
      against 58 common aero-allergens and subjects with >=1 positive SPT were labeled
      as atopic. RESULTS: The BA-AR and BA groups had higher FENO levels in comparison
      to the control (P < 0.05) and AR group (P < 0.05). The AR and BA-AR groups had
      higher n NO levels compared to the control group (P < 0.05) and BA group (P <
      0.05). The increasing FENO levels significantly correlated with the increase in
      the number of allergen sensitization in patients suffering from BA-AR (P < 0.05).
      However, the BA group showed a weaker positive correlation (P = 0.07).
      CONCLUSION: FENO is a non-invasive marker of airway inflammation. Also, FENO
      levels correlate with presence and degree of atopy in BA and AR. Simultaneously,
      n NO could be a surrogate marker of rhinitis.

PMID- 25378842
TI  - A comparative study of different dose fractionations schedule of thoracic
      radiotherapy for pain palliation and health-related quality of life in metastatic
      NSCLC.
AB  - INTRODUCTION: To investigate the effect of different hypo fractionated thoracic
      radiotherapy schedules in relation to thoracic pain relief, overall survival and
      post radiotherapy HRQOL in metastatic NSCLC. MATERIAL AND METHODS: Stage IV NSCLC
      and had intra-thoracic symptoms, included in the study. Patients were randomly
      assigned to three treatments arms. (i) 17 Gy in 2 fractions in one week (ii) 20
      Gy in five fractions in one week. (iii) 30 Gy in 10 fractions in two weeks. BPI
      module was used to assess pain score before and after the thoracic radiotherapy.
      Functional assessment of cancer therapy-G (FACT-G) used to investigate changes in
      HRQOL. Clinicians' assessment of symptom improvement were recorded at 2(nd),
      6(th) and 12(th) weeks after completion of TRT. RESULTS: Pain relief, HRQOL and
      OS were equivalent in all the three arms. The median OS were 6 months, 5 months,
      6 months in arm A, B and arm C, respectively. CONCLUSION: Protracted palliative
      thoracic radiotherapy renders no added advantage of relief of symptoms, HRQOL and
      overall survival compared to short course palliative TRT in metastatic NSCLC.

PMID- 25378843
TI  - Spectrum of diffuse parenchymal lung diseases with special reference to
      idiopathic pulmonary fibrosis and connective tissue disease: An eastern India
      experience.
AB  - OBJECTIVE: To evaluate the clinical spectrum of diffuse parenchymal lung diseases
      (DPLD) encountered in the Indian setting and to compare idiopathic pulmonary
      fibrosis (IPF) and connective tissue disease associated DPLD (CTD-DPLD), the two
      commonest aetiologies. MATERIALS AND METHODS: A prospective study of clinical,
      imaging and laboratory parameters of patients diagnosed as DPLD and followed up
      in the Pulmonary Medicine Department of a tertiary-care teaching institution in
      eastern India was conducted over a period of one year. RESULTS: 92 patients of
      DPLD were diagnosed in the study period with IPF (n = 35, 38.04%), CTD-DPLD (n =
      29, 31.5%), hypersensitivity pneumonitis (n = 10, 10.9%), sarcoidosis (n = 5,
      5.4%) and silicosis (n = 5, 5.4%) being the common causes. The CTD-DPLD group had
      a lower mean age (39.5 +/- 1.86 vs 56.9 +/- 1.12 years), a longer duration of
      symptoms (3.5 +/- 0.27 vs 2.5 +/- 0.26 years), more extra pulmonary
      manifestations, significantly more base line FVC and 6-minute-walk-distance than
      the IPF patients. 19 patients of IPF (54%) opted for treatment. All the IPF
      patients had a significant fall in FVC after six months (mean change -0.203 +/-
      0.01 litres) compared to the CTD-DPLD group (mean change - 0.05 +/- 0.04
      litres.). CONCLUSION: CTD-DPLD patients belong to a younger age group, with
      longer duration of symptoms, more extrapulmonary features, better physiological
      parameters and better response to therapy than IPF patients. Larger prospective
      epidemiological studies and enrolment in clinical trials are necessary for better
      understanding of the spectrum of diffuse parenchymal lung disorders and their
      therapeutic options.

PMID- 25378844
TI  - Evaluation of the effect of pulmonary hydatid cyst location on the surgical
      technique approaches.
AB  - PURPOSE: A hydatid cyst is the most common lung parasitic disease and is endemic
      in Iran. A hydatid cyst is more common in the right lung and lower lobes.
      OBJECTIVE: The aim of this study was to assess surgical treatment of pulmonary
      hydatid cysts and whether the location of cyst affects surgical technique
      approaches. MATERIALS AND METHODS: This study was performed on 87 patients with a
      pulmonary hydatid cyst who were referred to Qaem Hospital from 2010 to 2012.
      Selection of surgical technique was according to size, location, and the number
      of cysts. Patients were divided into two groups: (1) surgery with preserving lung
      parenchyma and (2) lobectomy. Afterward, the relationship between the location of
      cyst and surgical technique approaches was evaluated. Data was analyzed by Chi
      square and Fisher exact tests. RESULTS: In this study, no significant relation
      was found between the size (P = 0.682) and number (P = 0.344) of cysts and
      lobectomy necessity. But, there was a significant relation between the occurrence
      of cyst in middle lobe and lobectomy necessity (P = 0.016). CONCLUSIONS:
      According to the results, type of surgical technique does not depend on the size
      and number of cysts, but it may be related to the location of the cyst and the
      ratio of lung destruction.

PMID- 25378845
TI  - Ease-of-use, preference, confidence, and satisfaction with Revolizer((r)), a
      novel dry powder inhaler, in an Indian population.
AB  - CONTEXT: While prescribing an inhaler device, it is important to take into
      account the usability, preference, confidence, and satisfaction of the patients.
      AIMS: The present study assessed these parameters with Revolizer((r)), a novel
      dry powder inhaler (DPI), in patients with obstructive airway diseases and in
      device-naive healthy participants. SETTINGS AND DESIGN: In this open-label,
      prospective, multicentre study with 100 participants [n = 50 healthy
      participants, n = 45 mild asthma patients, and n = 5 mild chronic obstructive
      pulmonary disease (COPD) patients], all participants were instructed and trained
      on the use of Revolizer and then the participants subsequently demonstrated the
      inhalation technique at two visits. MATERIALS AND METHODS: The average time
      required to execute three correct consecutive attempts and the number of errors
      (including critical errors) were recorded. Participants were asked about the ease
      of use, preference, confidence, and satisfaction by means of a questionnaire at
      each visit. RESULTS: The average time required by the participants to achieve
      three correct consecutive attempts at visit 1 was 3.75 +/- 2.10 min, which
      significantly reduced at visit 2 (3.07 +/- 1.32 min, P < 0.01). The number of
      errors decreased from visit 1 to visit 2. More than 85% participants found the
      Revolizer easy to use, and it was preferred by more than 75% participants.
      Revolizer scored high on the confidence and satisfaction of all participants at
      both visits. CONCLUSIONS: Revolizer is an easy-to-use and a preferred device in
      patients with mild asthma and COPD, as well as in healthy participants with no
      previous experience of using inhalation devices. The participants felt confident
      and satisfied using the Revolizer.

PMID- 25378846
TI  - Potential impact of fireworks on respiratory health.
AB  - The world-wide use of fireworks with their consequent detrimental effect on the
      air quality is widely recognized with elevated ambient air levels of particulate
      matter and its several metallic components and gases identified in several
      studies carried out during such events. Exposed individuals may be at risk
      following inhalation of such produced pollutants. This review focuses on the
      impact of fireworks on air quality and the potential effect of fireworks on the
      respiratory system of healthy individuals as well as those suffering from
      underlying respiratory diseases, particularly asthma and chronic obstructive
      pulmonary disease (COPD). This applies not only to spectators including children
      but also to pyrotechnicians themselves. An extensive Medline search revealed that
      a strong evidence of the impact of fireworks on respiratory health is lacking in
      susceptible as well as healthy individuals with no formal studies on COPD or
      asthma, other than a few case reports in the latter. The implementation of global
      strategies to control the use of fireworks and hence improve air quality could
      possibly reduce their likely detrimental effect on human respiratory health in
      exposed individuals, but clearly a more targeted research is needed. 

PMID- 25378847
TI  - Pleuro-peritoneal lymphomatosis with concurrent tonsillar involvement in T-cell
      nonHodgkin's lymphoma: Clinical presentation mimicking disseminated tuberculosis.
AB  - A young male patient had been evaluated for pleural effusion at another center
      wherein on the basis of exudative, lymphocyte predominant pleural effusion with
      high pleural fluid adenosine deaminase (ADA) levels and tuberculin skin test
      (TST) reactivity, antituberculous medications had been administered. Reevaluation
      in view of worsening symptoms led to confirmation of the diagnosis of T-cell
      lymphoblastic lymphoma with pleuro-peritoneal lymphomatosis and tonsillar
      involvement. This case highlights the fact that elevated ADA levels should not be
      taken as surrogate for a diagnosis of TB in the absence of
      histopathological/microbiological confirmation even in countries with high
      tuberculosis (TB) prevalence. Tonsil in an uncommon site of involvement in
      patients with T-cell lymphoma. As the diagnosis in our patient was confirmed from
      biopsy of a tonsillar mass, a thorough physical examination should be performed
      in all patients with a suspected diagnosis of lymphoma. 

PMID- 25378848
TI  - Superior vena caval syndrome and ipsilateral pleural effusion: A rare
      presentation of anterior mediastinal thymoma.
AB  - Incidence of thymic malignancies is very low. Thymoma, a tumor of thymus gland,
      is of epithelial origin and is most common anterior mediastinal tumor. In most
      cases, thymomas are localized and locally advanced thymomas may rarely present
      with superior vena caval obstruction (SVCO) and malignant pleural deposits.
      Microscopically, capsular invasion is noted in case of locally advanced thymomas,
      which behave like a malignant neoplasm. Complete surgical removal of the tumor
      along with intact capsule is the treatment modality of choice in case of
      localized tumors. Neoadjuvant radiotherapy (RT) and chemotherapy followed by
      surgical resection of residual tumor is useful in case of locally advanced
      tumors. RT is especially useful in case of SVCO to relieve the distressing
      respiratory symptoms. Here, we report a rare case of locally advanced thymoma,
      complicated by SVCO and ipsilateral pleural effusion in a 53-year-old male
      patient. 

PMID- 25378849
TI  - Surgical lung biopsy to diagnose Behcet's vasculitis with adult respiratory
      distress syndrome.
AB  - A 34-year-old female presented with fever and abdominal pain. Past medical
      history includes Crohn's and Behcet's disease. Examination revealed multiple skin
      ulcerations, oral aphthae, and bilateral coarse rales. She developed respiratory
      distress with diffuse bilateral alveolar infiltrates on chest radiograph
      requiring intubation. PaO2/FiO2 ratio was 132. The chest computed tomography
      revealed extensive nodular and patchy ground-glass opacities. Bronchoalveolar
      lavage demonstrated a predominance of neutrophils. Methylprednisolone 60 mg every
      6 h and broad-spectrum antimicrobials were initiated. No infectious etiologies
      were identified. Surgical lung biopsy demonstrated diffuse alveolar damage (DAD)
      mixed with lymphocytic and necrotizing vasculitis with multiple small infarcts
      and thrombi consistent with Behcet's vasculitis. As she improved, steroids were
      tapered and discharged home on oral cyclophosphamide. Pulmonary involvement in
      Behcet's is unusual and commonly manifests as pulmonary artery aneurysms,
      thrombosis, infarction, and hemorrhage. Lung biopsy findings demonstrating DAD
      are consistent with the clinical diagnosis of adult respiratory distress
      syndrome. The additional findings of necrotizing vasculitis and infarcts may have
      led to DAD. 

PMID- 25378850
TI  - Bilateral pleural effusion with APLA positivity in a case of rhupus syndrome.
AB  - Rhupus syndrome is a rare syndrome characterized by overlap of rheumatoid
      arthritis (RA) and systemic lupus erythematosus (SLE). Our patient was a
      diagnosed case of RA and developed SLE 2 years after. She was a middle-aged
      woman, presented with bilateral pleural effusion with exacerbation of skin and
      joint symptoms of SLE. We diagnosed the case as tubercular pleural effusion by
      positive Mycobacterium tuberculosis in bactec 460 culture. She had also anti
      phospholipid antibody positivity without any symptoms and signs of thrombosis. 

PMID- 25378851
TI  - Common variable immunodeficiency disorder - An uncommon cause for bronchiectasis.
AB  - Bronchiectasis continues to be a common respiratory problem of varied etiology.
      Common variable immunodeficiency disorder (CVID) is an uncommon cause for
      bronchiectasis. However, the prevalence of bronchiectasis remains very high in
      patients with CVID. This remains largely an underdiagnosed entity as primary
      immunodeficiency is not suspected in adults as a cause of bronchiectasis and
      hence, serum immunoglobulin (Ig) levels are not measured routinely. In addition
      to bronchiectasis, patients with CVID usually present with various extrapulmonary
      symptoms. I report here a case of young man who presented with bronchiectasis and
      multisystem complains who was diagnosed as CVID. 

PMID- 25378852
TI  - Granulomatosis with polyangitis with mononeuritis multiplex-immunosuppressives
      playing a double-edged sword.
AB  - A 52-year-old female was diagnosed with rheumatoid arthritis and was on
      methotrexate and prednisolone. She developed fever, cough, hemoptysis, and
      cavitary lesion on chest skiagram. She was put on antitubercular therapy without
      any improvement, meanwhile she developed painful right foot drop.
      Clinicoradiology and C-ANCA study confirmed the diagnosis of granulomatosis with
      polyangitis (GPA). She was started on cyclophosphamide, corticosteroid, and co
      trimoxazole. While her treatment was being continued she showed significant
      improvement of pulmonary manifestations. About 1 year later, there was
      reappearance of fever, cough, and radiological opacity with oropharyngeal
      candidiasis. She became very ill with disseminated intravascular coagulation
      (DIC)-like features. Immunological markers were negative but bronchoalveolar
      lavage fluid study showed growth of Aspergillus spp. The patient was promptly put
      on intravenous voriconazole but unfortunately she succumbed to her illness. 

PMID- 25378853
TI  - Endobronchial ultrasound guided needle aspiration of a paraspinal mass with prior
      failed multiple diagnostic interventions: A case report and literature review.
AB  - The increasing frequency of tuberculosis (TB) in both developed and developing
      countries has continued to make spinal TB an important health problem. The
      present case report is about a patient who presented to us with progressive back
      pain and paraspinal mass. We performed endobronchial ultrasound guided needle
      aspiration from the paraspinal mass. The cytology showed granulomatous
      inflammation suggestive of TB. 

PMID- 25378854
TI  - Primary amyloidoma of lung treated with radiation: A rare case report.
AB  - Amyloidosis is a collection of diseases in which different proteins are deposited
      as insoluble beta-pleated sheets, disrupting organ function. Distribution of
      these deposits may be diffuse or localized throughout the body, depending on the
      pathophysiology of the underlying amyloid type. Isolated deposition of amyloid
      proteins in lung is a very rare entity. They are frequently misdiagnosed as
      bronchogenic carcinoma, metastatic disease, or focal fungal infections. The
      treatment of solitary pulmonary amyloidosis is not well-defined. We have treated
      a 65-year-old female patient with external beam radiation and corticosteroids in
      palliative intent and she is leading a good quality of life after six months of
      follow up. 

PMID- 25378855
TI  - Shrinking lung syndrome in systemic lupus erythematosus-scleroderma overlap.
AB  - Shrinking lung syndrome (SLS) is a infrequently reported manifestation of
      systemic lupus erythematosus (SLE). Reported prevalence of SLS is about 0.5% in
      SLE patients. Pathogenesis is not fully understood and different therapeutic
      modalities have been employed with variable results, as only 77 cases of SLS have
      been documented in literature. SLS in SLE-Scleroderma overlap has not been
      reported yet. We report a patient of SLE - scleroderma overlap presenting with
      dyspnea, intermittent orthopnea and pleuritic chest pain. Evaluation revealed
      elevated hemidiaphragms and severe restrictive defect. She was eventually
      diagnosed as a case of SLS. This case report is a reminder to the medical
      fraternity that SLS although a rare complication must be thought of in the
      special subset of patients of SLE having respiratory symptoms. 

PMID- 25378856
TI  - Pulmonary tumor thrombotic microangiopathy in an unknown primary cancer.
AB  - Pulmonary tumor thrombotic microangiopathy (PTTM) is a highly fatal complication
      of cancer leading to acute cor pulmonale and pulmonary hypertension. We present a
      case of 47-year-old male patient who developed acute breathlessness and died
      suddenly. The pulmonary vessels at autopsy on histopathologic examination showed
      the presence of fibrocellular intimal proliferation, fibrin thrombi and few tumor
      emboli consisting of malignant adenocarcinoma cells. There was associated
      lymphangiosis carcinomatosis. No primary visceral tumor was found despite
      extensive search. The patient had died following acute cor pulmonale with sudden
      pulmonary hypertension due to PTTM. This entity (PTTM) must be kept as a
      differential diagnosis in patients presenting with acute breathlessness
      especially in cases of cancers. 

PMID- 25378857
TI  - An extremely unusual presentation of isolated extrathoracic sarcoidosis of
      submandibular lymph node in a child.
AB  - A 12-year-old male child presented with left submandibular lymphadenopathy;
      excision biopsy revealed noncaseating granuloma with numerous Schaumann bodies in
      histopathology, suggestive of isolated extrathoracic sarcoidosis, which is an
      extremely rare entity in the pediatric age group. 

PMID- 25378858
TI  - Completely opaque hemithorax.

PMID- 25378859
TI  - Tracheal compression due to anomalous innominate artery in an adult.
AB  - A 47-year-old-female presented with dyspnea and unproductive cough for 4 months.
      General examination revealed pulsatile swelling in the midline below the thyroid
      cartilage present since childhood. Computed tomography-angiography of the neck
      showed right innominate artery dilated, elongated and coursing above downward,
      anterior to the trachea below the thyroid, compressing the trachea and origin of
      the right subclavian artery higher up. A case of anomalous innominate artery
      causing symptomatic compression of the trachea in adults is a rare entity. 

PMID- 25378860
TI  - Eventration of the right hemidiaphragm with multiple associations: A rare
      presentation.

PMID- 25378861
TI  - A case of recurrent massive right sided pleural effusion-an unusual presentation
      of carcinoma prostate.

PMID- 25378862
TI  - Protecting ourselves from tuberculosis. Describing a historic poster printed in
      italy on 1937.

PMID- 25378863
TI  - An increasingly breathless patient.

PMID- 25378864
TI  - Mobile vegetation leading to septic pulmonary embolism.

PMID- 25378865
TI  - Relationship between lung function and indoor air pollution.

PMID- 25378866
TI  - Author's reply.

PMID- 25378867
TI  - Bhang - beyond the purview of the narcotic drugs and psychotropic substances act.

PMID- 25378868
TI  - Author's reply.

PMID- 25378869
TI  - Adenosine deaminase in exudative pleural effusions.

PMID- 25378870
TI  - Author's reply.

PMID- 25378872
TI  - An eye for an eye.

PMID- 25378871
TI  - Glyco-epitope Diversity: An Evolving Area of Glycomics Research and Biomarker
      Discovery.

PMID- 25378873
TI  - Vascular endothelial growth factor trap-eye and trap technology: Aflibercept from
      bench to bedside.
AB  - Anti-vascular endothelial growth factor (VEGF) currently used to treat eye
      diseases have included monoclonal antibodies, antibody fragments, and an aptamer.
      A different method of achieving VEGF blockade in retinal diseases includes the
      concept of a cytokine trap. Cytokine traps technology are being evaluated for the
      treatment of various diseases that are driven by excessive cytokine levels. Traps
      consist of two extracellular cytokine receptor domains fused together to form a
      human immunoglobulin G (IgG). Aflibercept/VEGF trap-eye (VTE) is a soluble fusion
      protein, which combines ligand-binding elements taken from the extracellular
      components of VEGF receptors 1 and 2 fused to the Fc portion of IgG. This protein
      contains all human amino acid sequences, which minimizes the potential for
      immunogenicity in human patients. This review presents the latest data on VTE in
      regard to the pharmacokinetics, dosage and safety, preclinical and clinical
      experiences. Method of the literature search: A systematic search of the
      literature was conducted on PubMed, Scopus, and Google Scholar with no limitation
      on language or year of publication databases. It was oriented to articles
      published for VTE in preclinical and clinical studies and was focused on the
      pharmacokinetics, dosage and safety of VTE. 

PMID- 25378874
TI  - Long term refractive and structural outcome following laser treatment for zone 1
      aggressive posterior retinopathy of prematurity.
AB  - AIM: To report the long term refractive, visual and structural outcome post-laser
      for zone 1 aggressive posterior retinopathy of prematurity (AP-ROP). MATERIALS
      AND METHODS: A retrospective analysis was performed of refractive status of
      premature infants with zone 1 AP-ROP who underwent laser photocoagulation from
      2002 to 2007 and followed up till 2013. Once the disease regressed, children were
      followed up six monthly with detailed examination regarding fixation pattern,
      ocular motility, nystagmus, detailed anterior segment and posterior segment
      examination, and refractive status including best corrected visual acuity.
      RESULTS: Forty-eight eyes of 25 infants were included in the study. Average
      follow-up was 6.91 years (range, 3.8-9.5years) after laser treatment. Astigmatism
      was noted in 43 out of 48 eyes (89.6%). Two eyes had simple myopia whereas three
      eyes had no refractive error. CONCLUSION: After successful laser treatment for
      zone 1 retinopathy of prematurity (ROP), 94% of our cases developed refractive
      error. Although most had a favorable anatomical and visual outcome, long-term
      follow-up even after a successful laser treatment in ROP was necessary.

PMID- 25378875
TI  - Influence of visual angle on pattern reversal visual evoked potentials.
AB  - PURPOSE: The aim of this study was to find whether the visual evoked potential
      (VEP) latencies and amplitude are altered with different visual angles in healthy
      adult volunteers or not and to determine the visual angle which is the optimum
      and most appropriate among a wide range of check sizes for the reliable
      interpretation of pattern reversal VEPs (PRVEPs). MATERIALS AND METHODS: The
      present study was conducted on 40 healthy volunteers. The subjects were divided
      into two groups. One group consisted of 20 individuals (nine males and 11
      females) in the age range of 25-57 years and they were exposed to checks
      subtending a visual angle of 90, 120, and 180 minutes of arc. Another group
      comprised of 20 individuals (10 males and 10 females) in the age range of 36-60
      years and they were subjected to checks subtending a visual angle of 15, 30, and
      120 minutes of arc. The stimulus configuration comprised of the transient pattern
      reversal method in which a black and white checker board is generated (full
      field) on a VEP Monitor by an Evoked Potential Recorder (RMS EMG. EPMARK II). The
      statistical analysis was done by One Way Analysis of Variance (ANOVA) using EPI
      INFO 6. RESULTS: In Group I, the maximum (max.) P100 latency of 98.8 +/- 4.7 and
      the max. P100 amplitude of 10.05 +/- 3.1 MUV was obtained with checks of 90
      minutes. In Group II, the max. P100 latency of 105.19 +/- 4.75 msec as well as
      the max. P100 amplitude of 8.23 +/- 3.30 MUV was obtained with 15 minutes. The
      min. P100 latency in both the groups was obtained with checks of 120 minutes
      while the min. P100 amplitude was obtained with 180 minutes. A statistically
      significant difference was derived between means of P100 latency for 15 and 30
      minutes with reference to its value for 120 minutes and between the mean value of
      P100 amplitude for 120 minutes and that of 90 and 180 minutes. CONCLUSION:
      Altering the size of stimulus (visual angle) has an effect on the PRVEP
      parameters. Our study found that the 120 is the appropriate (and optimal) check
      size that can be used for accurate interpretation of PRVEPs. This will help in
      better assessment of the optic nerve function and integrity of anterior visual
      pathways.

PMID- 25378876
TI  - Spectral domain optical coherence tomography characteristics in diabetic
      retinopathy.
AB  - PURPOSE: To report the appearance of diabetic retinopathy lesions using spectral
      domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: A total of
      287 eyes of 199 subjects were included. All the subjects underwent complete
      ophthalmic examination including SD-OCT. RESULTS: The appearance of various
      lesions of diabetic retinopathy and the retinal layers involved were reported. In
      subjects with macular edema the prevalence of incomplete PVD was 55.6%.
      CONCLUSION: SD-OCT brings new insights into the morphological changes of the
      retina in diabetic retinopathy.

PMID- 25378877
TI  - Outcome of rhegmatogenous retinal detachment repair by scleral buckling: The
      experience of a tertiary referral center in Scotland.
AB  - PURPOSE: The primary aim of this study is to report the outcome of patients with
      rhegmatogenous retinal detachment (RRD) who underwent scleral buckling (SB)
      surgery. METHODS: This is a retrospective noncomparative case series study of all
      patients who underwent RRD repair by primary SB between March 2008 and February
      2009. Patient demographics, visual outcome, complications, and failure rates were
      identified and recorded. RESULTS: A total of 65 patients underwent RRD repair by
      SB, with a mean age of 44.44 years. Results showed that the primary outcome
      (primary anatomical success following index surgery) was 90.77%, while the
      secondary outcome (anatomical success following repeat surgery) was 98.46%.
      CONCLUSION: The study showed a high-success rate of SB in phakic eyes both in
      terms of postoperative best-corrected visual acuity and complication rates. We
      recommend the continued use of this technique in selected cases of RRD.

PMID- 25378878
TI  - Bilateral familial vertical Duane Syndrome with synergistic convergence, aberrant
      trigeminal innervation, and facial hypoplasia.
AB  - A 5-year-old girl presented with bilateral familial vertical Duane retraction
      syndrome with alternating esotropia, elevation deficit, Marcus gunn phenomenon,
      and facial hypoplasia. Abnormal adducting downshoots on attempting abduction
      suggestive of a synergistic convergence were noted. Hypothesis suggests aberrant
      innervations or peripheral anatomic connections between inferior and medial
      recti. 

PMID- 25378879
TI  - Resistant retinoblastoma in a 23-year-old patient.
AB  - Retinoblastoma is a very rare disease in adults. We are reporting a rare case of
      resistant retinoblastoma in 23-year-old patient. A 23-year-old male patient
      presented with loss of vision in the right eye over one-month duration.
      Examination showed an epiretinal membrane in the right macula in addition to a
      white mass located inferiorly and associated with vitreous seeds. The diagnosis
      of retinoblastoma was established. In order to save the patient's life and to
      preserve the eye and vision, he was treated with chemotherapy, focal therapy, and
      radioactive Iodine(125) plaque therapy. The tumor was resistant for treatment and
      recurred two years after plaque therapy, and enucleation showed well
      differentiated retinoblastoma. Retinoblastoma may present in adults, and it was
      resistant to both chemotherapy and plaque radiation therapy in our case. 

PMID- 25378880
TI  - Paediatric choroidal neovascular membrane secondary to toxoplasmosis treated
      successfully with anti-vascular endothelial growth factor.
AB  - The purpose of this report was to evaluate the role anti-VEGF in management of
      CNVM secondary to ocular toxoplasmosis. Young female diagnosed as a case of
      bilateral ocular toxoplasmosis presented with complaints of diminution of vision
      in the right eye. Fundus examination showed an active CNVM adjacent to
      toxoplasmosis scar. In view of active CNVM, patient was administered intravitreal
      ranibizumab. A total of 2 injections of intravitreal ranibizumab were given.
      Fundus showed a scarred CNVM adjacent to the toxoplasma scar with no clinical
      signs of activity. Anti-VEGF therapy has been successfully used to improve visual
      and anatomical outcome in juxtafoveal (deleted subfoveal)CNVM secondary to
      toxoplasmosis. 

PMID- 25378881
TI  - A case of submacular cysticercosis treated by pars plana vitrectomy in Kuwait.
AB  - We report a case of submacular cysticercosis in the left eye of an Indian patient
      living in Kuwait. Though he was systemically asymptomatic, his magnetic resonance
      imaging showed multiple cysts in the brain. The patient underwent pars plana
      vitrectomy (PPV), and the cyst was removed in total through a retinotomy over the
      cyst. He had another small cyst in the periphery that was also removed. He was
      treated with oral albendazole and systemic steroids after the surgery to treat
      his neurocysticercosis. He developed rhegmatogenous retinal detachment after the
      surgery, and the retina was successfully reattached with scleral buckling and PPV
      procedure. His final best corrected visual acuity improved from counting fingers
      at 1/2 m at presentation to 20/400. This case report shows that the ocular
      cysticercosis may be seen among expatriates working in the Middle East. It is
      important to rule out the presence of neurocysticercosis in such patients as well
      as multiple cysts in the affected eye. However, the functional outcome of
      surgical treatment of submacular cysticercosis can be disappointing. 

PMID- 25378882
TI  - Vitreous occlusion of tube implant in a phakic patient with traumatic glaucoma.
AB  - Tube implants or glaucoma drainage devices have become an important method of
      intraocular pressure reduction when treating complex cases of traumatic glaucoma.
      However, it is not uncommon to have complications associated with tube implants.
      The optimal treatment of patients who have undergone glaucoma implant surgery
      complicated by vitreous incarceration is uncertain. If vitreous is present or is
      able to prolapse into anterior chamber, as in aphakic or pseudophakic patient
      without an intact posterior capsule, a concurrent anterior vitrectomy is usually
      performed. In such cases, pars plana vitrectomy has been found to be more
      effective in several studies. However, there are no set guidelines for management
      of such a case in a phakic eye and the management can be more challenging
      especially when there is no obvious deficiency in posterior capsule, zonular
      dialysis, or loose vitreous gel in the anterior chamber prior to or during tube
      implantation. We describe a case of 14-year-old phakic patient with traumatic
      glaucoma without vitreous gel in anterior chamber whose tube implant became
      occluded by vitreous resulting in increased intra ocular pressure. This is the
      first documented report of vitreous incarceration in a phakic patient and its
      successful management. 

PMID- 25378883
TI  - Functional spasm of accommodation: Changes on scheimpflug imaging.
AB  - Spasm of accommodation is a rare condition characterized by a sudden increase in
      myopia. It can occur in emmetropes, hypermetropes and myopes. All the
      physiological changes that occur in normal accommodation are exaggerated. Mostly
      the cause is functional disorder and the condition gradually improves. We hereby
      present the changes occurring in spasm of accommodation as seen on Scheimpflug
      imaging. 

PMID- 25378884
TI  - Ocular findings in a case of periorbital giant congenital melanocytic nevus.
AB  - Giant congenital melanocytic nevus (GCMN) is a large melanocytic nevus that
      rarely occurs in the periorbital region. Various systemic, as well as ophthalmic
      associations, have been reported with GCMN. However, there is only one case
      report describing ophthalmic findings in periorbital GCMN. We describe the ocular
      findings in a case of periorbital GCMN. 

PMID- 25378886
TI  - Interdisciplinary approach: A boon for ocular rehabilitation.

PMID- 25378887
TI  - A 48-year-old female with sudden onset of painless diminution of vision in left
      eye.

PMID- 25378888
TI  - Pre-macular hemorrhage in chronic malaria.

PMID- 25378889
TI  - External ophthalmomyiasis.

PMID- 25378890
TI  - Recurrent microbial keratitis in eyes with keratoconjunctivitis sicca with
      coexisting ocular surface pathology.

PMID- 25378892
TI  - Predictors of Parenting and Infant Outcomes for Impoverished Adolescent Parents.
AB  - Adolescent mothers and their children are at risk for a myriad of negative
      outcomes. This study examined risk and protective factors and their impact on a
      sample (N=172) of impoverished adolescent mothers. Multiple regression analyses
      revealed that depressed adolescent mothers report higher levels of parenting
      stress, and that their children are more at risk for maltreatment and are
      developmentally behind other babies. In addition, adolescent mothers with
      restricted social support have babies who are at higher risk for maltreatment.
      Finally, mothers who were older during pregnancy were more likely to stay in
      school. Implications for program development are discussed.

PMID- 25378891
TI  - INTRACELLULAR SIGNALING BY BILE ACIDS.
AB  - Bile acids, synthesized from cholesterol, are known to produce beneficial as well
      as toxic effects in the liver. The beneficial effects include choleresis,
      immunomodulation, cell survival, while the toxic effects include cholestasis,
      apoptosis and cellular toxicity. It is believed that bile acids produce many of
      these effects by activating intracellular signaling pathways. However, it has
      been a challenge to relate intracellular signaling to specific and at times
      opposing effects of bile acids. It is becoming evident that bile acids produce
      different effects by activating different isoforms of phosphoinositide 3-kinase
      (PI3K), Protein kinase Cs (PKCs), and mitogen activated protein kinases (MAPK).
      Thus, the apoptotic effect of bile acids may be mediated via PI3K-110gamma, while
      cytoprotection induce by cAMP-GEF pathway involves activation of PI3K
      p110alpha/beta isoforms. Atypical PKCzeta may mediate beneficial effects and
      nPKCepsilon may mediate toxic effects, while cPKCalpha and nPKCdelta may be
      involved in both beneficial and toxic effects of bile acids. The opposing effects
      of nPKCdelta activation may depend on nPKCdelta phosphorylation site(s).
      Activation of ERK1/2 and JNK1/2 pathway appears to mediate beneficial and toxic
      effects, respectively, of bile acids. Activation of p38alpha MAPK and p38beta
      MAPK may mediate choleretic and cholestatic effects, respectively, of bile acids.
      Future studies clarifying the isoform specific effects on bile formation should
      allow us to define potential therapeutic targets in the treatment of cholestatic
      disorders.

PMID- 25378894
TI  - Lateral migration of a viscoelastic drop in a Newtonian fluid in a shear flow
      near a wall.
AB  - Wall induced lateral migration of a viscoelastic (FENE-MCR) drop in a Newtonian
      fluid is investigated. Just like a Newtonian drop, a viscoelastic drop reaches a
      quasi-steady state where the lateral velocity only depends on the instantaneous
      distance from the wall. The drop migration velocity and the deformation scale
      inversely with the square and the cube of the distance from the wall,
      respectively. The migration velocity varies non-monotonically with increasing
      viscoelasticity (increasing Deborah number); initially increasing and then
      decreasing. An analytical explanation has been given of the effects by computing
      the migration velocity as arising from an image stresslet field due to the drop.
      The semi-analytical expression matches well with the simulated migration velocity
      away from the wall. It contains a viscoelastic stresslet component apart from
      those arising from interfacial tension and viscosity ratio. The migration
      dynamics is a result of the competition between the viscous (interfacial tension
      and viscosity ratio) and the viscoelastic effects. The viscoelastic stresslet
      contribution towards the migration velocity steadily increases. But the
      interfacial stresslet-arising purely from the drop shape-first increases and then
      decreases with rising Deborah number causing the migration velocity to be non
      monotonic. The geometric effect of the interfacial stresslet is caused by a
      corresponding nonmonotonic variation of the drop inclination. High viscosity
      ratio is briefly considered to show that the drop viscoelasticity could stabilize
      a drop against breakup, and the increase in migration velocity due to
      viscoelasticity is larger compared to the viscosity-matched case.

PMID- 25378893
TI  - Bayesian Semiparametric Density Deconvolution in the Presence of Conditionally
      Heteroscedastic Measurement Errors.
AB  - We consider the problem of estimating the density of a random variable when
      precise measurements on the variable are not available, but replicated proxies
      contaminated with measurement error are available for sufficiently many subjects.
      Under the assumption of additive measurement errors this reduces to a problem of
      deconvolution of densities. Deconvolution methods often make restrictive and
      unrealistic assumptions about the density of interest and the distribution of
      measurement errors, e.g., normality and homoscedasticity and thus independence
      from the variable of interest. This article relaxes these assumptions and
      introduces novel Bayesian semiparametric methodology based on Dirichlet process
      mixture models for robust deconvolution of densities in the presence of
      conditionally heteroscedastic measurement errors. In particular, the models can
      adapt to asymmetry, heavy tails and multimodality. In simulation experiments, we
      show that our methods vastly outperform a recent Bayesian approach based on
      estimating the densities via mixtures of splines. We apply our methods to data
      from nutritional epidemiology. Even in the special case when the measurement
      errors are homoscedastic, our methodology is novel and dominates other methods
      that have been proposed previously. Additional simulation results, instructions
      on getting access to the data set and R programs implementing our methods are
      included as part of online supplemental materials.

PMID- 25378895
TI  - Dynamics of Magnetic Nanoparticle-Based Contrast Agents in Tissues Tracked Using
      Magnetomotive Optical Coherence Tomography.
AB  - Magnetomotive optical coherence tomography (MM-OCT) is an important tool for the
      visualization and quantitative assessment of magnetic nanoparticles in tissues.
      In this study, we demonstrate the use of MM-OCT for quantitative measurement of
      magnetic iron oxide nanoparticle transport and concentration in ex vivo muscle,
      lung, and liver tissues. The effect of temperature on the dynamics of these
      nanoparticles is also analyzed. We observe that the rate of transport of
      nanoparticles in tissues is directly related to the elasticity of tissues, and
      describe how the origin of the MM-OCT signal is associated with nanoparticle
      binding. These results improve our understanding of how iron oxide nanoparticles
      behave dynamically in biological tissues, which has direct implications for
      medical and biological applications of targeted nanoparticles for contrast
      enhancement and therapy.

PMID- 25378896
TI  - Magnetically Actuated Soft Capsule With the Multimodal Drug Release Function.
AB  - In this paper, we present a magnetically actuated multimodal drug release
      mechanism using a tetherless soft capsule endoscope for the treatment of gastric
      disease. Because the designed capsule has a drug chamber between both magnetic
      heads, if it is compressed by the external magnetic field, the capsule could
      release a drug in a specific position locally. The capsule is designed to release
      a drug in two modes according to the situation. In the first mode, a small amount
      of drug is continuously released by a series of pulse type magnetic field (0.01
      0.03 T). The experimental results show that the drug release can be controlled by
      the frequency of the external magnetic pulse. In the second mode, about 800 mm3
      of drug is released by the external magnetic field of 0.07 T, which induces a
      stronger magnetic attraction than the critical force for capsule's collapsing. As
      a result, a polymeric coating is formed around the capsule. The coated area is
      dependent on the drug viscosity. This paper presents simulations and various
      experiments to evaluate the magnetically actuated multimodal drug release
      capability. The proposed soft capsules could be used as minimally invasive
      tetherless medical devices with therapeutic capability for the next generation
      capsule endoscopy.

PMID- 25378897
TI  - MRI-Safe Robot for Endorectal Prostate Biopsy.
AB  - This paper reports the development of an MRI-Safe robot for direct
      (interventional) MRI-guided endorectal prostate biopsy. The robot is constructed
      of nonmagnetic and electrically nonconductive materials, and is electricity free,
      using pneumatic actuation and optical sensors. Targeting biopsy lesions of MRI
      abnormality presents substantial clinical potential for the management of
      prostate cancer. The paper describes MRI-Safe requirements, presents the
      kinematic architecture, design and construction of the robot, and a comprehensive
      set of preclinical tests for MRI compatibility and needle targeting accuracy. The
      robot has a compact and simple 3 degree-of-freedom (DoF) structure, two for
      orienting a needle-guide and one to preset the depth of needle insertion. The
      actual insertion is performed manually through the guide and up to the preset
      depth. To reduce the complexity and size of the robot next to the patient, the
      depth setting DoF is remote. Experimental results show that the robot is safe to
      use in any MRI environment (MRI-Safe). Comprehensive MRI tests show that the
      presence and motion of the robot in the MRI scanner cause virtually no image
      deterioration or signal to noise ratio (SNR) change. Robot's accuracy in bench
      test, CT-guided in-vitro, MRI-guided in-vitro and animal tests are 0.37mm,
      1.10mm, 2.09mm, and 2.58mm respectively. These values are acceptable for clinical
      use.

PMID- 25378898
TI  - Design Studies of a CZT-based Detector Combined with a Pixel-Geometry-Matching
      Collimator for SPECT Imaging.
AB  - Single Photon Emission Computed Tomography (SPECT) suffers limited efficiency due
      to the need for collimators. Collimator properties largely decide the data
      statistics and image quality. Various materials and configurations of collimators
      have been investigated in many years. The main thrust of our study is to evaluate
      the design of pixel-geometry-matching collimators to investigate their potential
      performances using Geant4 Monte Carlo simulations. Here, a pixel-geometry
      matching collimator is defined as a collimator which is divided into the same
      number of pixels as the detector's and the center of each pixel in the collimator
      is a one-to-one correspondence to that in the detector. The detector is made of
      Cadmium Zinc Telluride (CZT), which is one of the most promising materials for
      applications to detect hard X-rays and gamma-rays due to its ability to obtain
      good energy resolution and high light output at room temperature. For our current
      project, we have designed a large-area, CZT-based gamma camera (20.192 cm*20.192
      cm) with a small pixel pitch (1.60 mm). The detector is pixelated and hence the
      intrinsic resolution can be as small as the size of the pixel. Materials of
      collimator, collimator hole geometry, detection efficiency, and spatial
      resolution of the CZT detector combined with the pixel-matching collimator were
      calculated and analyzed under different conditions. From the simulation studies,
      we found that such a camera using rectangular holes has promising imaging
      characteristics in terms of spatial resolution, detection efficiency, and energy
      resolution.

PMID- 25378899
TI  - Sequential occlusion of the branch retinal artery and branch retinal vein in a
      patient with hypertension: an interventional case report.
AB  - BACKGROUND: There are some cases that reported central retinal vein occlusion
      accompanied by ciliary artery occlusion, however, combined branch retinal artery
      and vein occlusion is a rare condition that has been infrequently reported. We
      describe in this report one case of retinal vein occlusion and branch retinal
      artery occlusion occurring simultaneously. CASE PRESENTATION: A 50 year-old woman
      presented with acute visual loss in her right eye. Fundus photography showed
      retinal ischemia and tortuous, dilated retinal veins in the right eye. With early
      phase fluorescein angiography, retinal arteries revealed areas absent of
      branches. Late phase fluorescein angiography demonstrated that areas absent of
      branches were still present. CONCLUSION: It is a rare case of branch retinal
      artery and vein occlusion.

PMID- 25378900
TI  - Successful treatment of neovascular age-related macular degeneration following
      single bevacizumab failure using aflibercept in a vitrectomized eye.
AB  - Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy in
      vitrectomized eyes remains a challenge due to the reduced half-life of these
      agents. Aflibercept may have stronger binding activity and a longer intravitreal
      half-life compared to bevacizumab and ranibizumab, but its use in postvitrectomy
      eyes has not been reported. We present a case of an 89-year-old female, with
      recurrent choroidal neovascularization 10 years following prior macular
      translocation vitrectomy surgery for neovascular age-related macular
      degeneration, successfully treated with monthly aflibercept injections initiated
      following poor response to a single initial bevacizumab injection. This report
      suggests that aflibercept may be an important treatment option for vitrectomized
      eyes requiring anti-VEGF treatment. 

PMID- 25378901
TI  - Bilateral endogenous Candida albicans subretinal abscess with suspected mixed
      bacterial infection.
AB  - PURPOSE: Candida albicans subretinal abscess is extremely rare. To our knowledge,
      only one unilateral case has been reported. Herein, we report one bilateral case.
      Mixed bacterial infection was also suspected based on broad-range real-time
      polymerase chain reaction. METHODS: A 64-year-old man being treated with oral
      corticosteroids for interstitial pneumonia visited us for visual loss in the left
      eye. Best corrected visual acuity (BCVA) was 20/20 in the right eye and 8/200 in
      the left eye. Funduscopy revealed round yellowish-white subretinal lesions with
      retinal hemorrhage in both eyes. RESULTS: Broad-range polymerase chain reaction
      of the vitreous fluid from the left eye showed a high copy count of bacterial 16s
      ribosome RNA. Despite large doses of antibiotics, the abscess expanded and vision
      decreased to light perception in the left eye. Exenteration of the left eye was
      performed followed by microscopic examination showing Gram-negative bacilli, and
      C. albicans was also cultured. Antibiotics and the maximum doses of antifungal
      drugs were administered. However, the abscess in the right eye expanded, and BCVA
      decreased to 2/200. Vitrectomy and silicone oil tamponade were performed.
      Vitreous fluid culture revealed C. albicans. At 16 months follow-up, BCVA was
      stable at 4/200 with healing of the subretinal abscess under silicone oil.
      CONCLUSION: Since C. albicans subretinal abscess is extremely rare and there was
      a concurrent mixed bacterial infection, diagnostic procedures in our bilateral
      case were more complicated than usual. C. albicans infection should be included
      in the differential diagnosis of subretinal abscesses.

PMID- 25378902
TI  - A retrospective study of the association between Fuchs' endothelial dystrophy and
      glaucoma.
AB  - OBJECTIVE: The goal of this study was to examine a possible clinical association
      between Fuchs' endothelial dystrophy (FED) and glaucoma suspect (GS)/ocular
      hypertension (OHT) or open angle glaucoma (OAG). METHODS: A retrospective chart
      review was carried out using data from electronic medical records and paper
      records from a private ophthalmology clinic in Kansas City, MO, USA. The review
      included 257 patients with FED and 584 randomly selected controls with no history
      of endothelial dystrophy. Binomial and multinomial regression using generalized
      estimating equations was used to create models to examine the correlation between
      FED diagnosis/severity and glaucoma diagnosis/type of glaucoma adjusted for age,
      sex, presence of diabetes, number of guttae, and intraocular pressure (IOP).
      RESULTS: No statistically significant increase in prevalence of either OHT or
      GS/OHT compared to controls was observed (P>0.3). There was a statistically
      significant positive correlation between increasing age and IOP with increased
      glaucoma prevalence (P<0.05). There was also a statistically significant positive
      correlation between increasing age, IOP and male sex, with increased prevalence
      of the more severe glaucoma subtype of OAG versus GS/OHT and controls (P<0.05).
      Increasing severity of FED divided into category 1 and 2 based upon number of
      guttae was not associated with any significant increase in glaucoma prevalence
      (P>0.09), and was actually significantly negatively correlated to worsening
      glaucoma subtype for category 2 FED patients (P<0.05). Diabetes was not
      associated with the prevalence of either glaucoma or its subtypes of GS/OHT or
      OAG. CONCLUSION: The correlation between FED and glaucoma has been controversial.
      This study showed no statistically significant association between FED and
      glaucoma by prevalence or severity of FED as measured by corneal guttae. Further
      study is needed to determine if a connection between FED and glaucoma does exist,
      and if so, whether this relationship may impact earlier the detection and
      treatment of disease.

PMID- 25378903
TI  - Surgical therapies for corneal perforations: 10 years of cases in a tertiary
      referral hospital.
AB  - PURPOSE: To report surgical therapies for corneal perforations in a tertiary
      referral hospital. METHODS: Thirty-one eyes of 31 patients (aged 62.4+/-18.3
      years) with surgically treated corneal perforations from January 2002 to July
      2013 were included in this study. Demographic data such as cause of corneal
      perforation, surgical procedures, and visual outcomes were retrospectively
      analyzed. RESULTS: The causes of corneal perforation (n=31) were divided into
      infectious (n=8, 26%) and noninfectious (n=23, 74%) categories. Infectious causes
      included fungal ulcer, herpetic stromal necrotizing keratitis, and bacterial
      ulcer. The causes of noninfectious keratopathy included corneal melting after
      removal of a metal foreign body, severe dry eye, lagophthalmos, canaliculitis,
      the oral anticancer drug S-1, keratoconus, rheumatoid arthritis, neurotrophic
      ulcer, atopic keratoconjunctivitis, and unknown causes. Initial surgical
      procedures included central large corneal graft (n=17), small corneal graft
      (n=7), and amniotic membrane transplantation (n=7). In two cases the perforation
      could not be sealed during the first surgical treatment and required subsequent
      procedures. All infectious keratitis required central large penetrating
      keratoplasty to obtain anatomical cure. In contrast, several surgical options
      were used for the treatment of noninfectious keratitis. After surgical treatment,
      anatomical cure was obtained in all cases. Mean postoperative best corrected
      visual acuity was better at 6 months (logMAR 1.3) than preoperatively (logMAR
      1.8). CONCLUSION: Surgical therapies for corneal perforations in our hospital
      included central large lamellar/penetrating keratoplasty, small peripheral patch
      graft, and amniotic membrane transplantation. All treatments were effective.
      Corneal perforation due to the oral anticancer drug S-1 is newly reported.

PMID- 25378904
TI  - Optic neuropathy associated with the use of over-the-counter sexual enhancement
      supplements.
AB  - This case report details an association of the use of over-the-counter sexual
      enhancement supplements with atypical optic neuropathy. A 42-year-old man
      presented with right-sided headache and vision loss of the right eye, which
      deteriorated to a single quadrant of hand motion over 11 days. Serial orbital
      magnetic resonance imaging scans demonstrated progressive orbital optic nerve
      enhancement extending into the optic canal despite high-dose steroid treatment.
      The patient eventually admitted to using several over-the-counter sexual
      enhancement supplements prior to the onset of symptoms and throughout the course
      of his steroid treatment, which he subsequently discontinued. His vision improved
      to 20/200 with an expanded visual field. Anterior ischemic optic neuropathy has
      been reported in association with phosphodiesterase (PDE)-5 inhibitor use, but
      visual loss in association with unregulated sexual enhancement supplements has
      not been studied. While one case cannot establish association, our case is
      suggestive of potential dangers of over-the-counter sexual enhancement
      supplements, which may contain PDE-5 inhibitors, "male hormones," and "substances
      that enhance blood production." The case also underscores the importance of
      obtaining a careful history of supplements in patients with optic neuropathies. 

PMID- 25378905
TI  - Preclinical profile of cabazitaxel.
AB  - First-generation taxanes have changed the treatment paradigm for a wide variety
      of cancers, but innate or acquired resistance frequently limits their use.
      Cabazitaxel is a novel second-generation taxane developed to overcome such
      resistance. In vitro, cabazitaxel showed similar antiproliferative activity to
      docetaxel in taxane-sensitive cell lines and markedly greater activity in cell
      lines resistant to taxanes. In vivo, cabazitaxel demonstrated excellent antitumor
      activity in a broad spectrum of docetaxel-sensitive tumor xenografts, including a
      castration-resistant prostate tumor xenograft, HID28, where cabazitaxel exhibited
      greater efficacy than docetaxel. Importantly, cabazitaxel was also active against
      tumors with innate or acquired resistance to docetaxel, suggesting therapeutic
      potential for patients progressing following taxane treatment and those with
      docetaxel-refractory tumors. In patients with tumors of the central nervous
      system (CNS), and in patients with pediatric tumors, therapeutic success with
      first-generation taxanes has been limited. Cabazitaxel demonstrated greater
      antitumor activity than docetaxel in xenograft models of CNS disease and
      pediatric tumors, suggesting potential clinical utility in these special patient
      populations. Based on therapeutic synergism observed in an in vivo tumor model,
      cabazitaxel is also being investigated clinically in combination with cisplatin.
      Nonclinical evaluation of the safety of cabazitaxel in a range of animal species
      showed largely reversible changes in the bone marrow, lymphoid system,
      gastrointestinal tract, and male reproductive system. Preclinical safety signals
      of cabazitaxel were consistent with the previously reported safety profiles of
      paclitaxel and docetaxel. Clinical observations with cabazitaxel were consistent
      with preclinical results, and cabazitaxel is indicated, in combination with
      prednisone, for the treatment of patients with hormone-refractory metastatic
      prostate cancer previously treated with docetaxel. In conclusion, the
      demonstrated activity of cabazitaxel in tumors with innate or acquired resistance
      to docetaxel, CNS tumors, and pediatric tumors made this agent a candidate for
      further clinical evaluation in a broader range of patient populations compared
      with first-generation taxanes. 

PMID- 25378906
TI  - Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole
      derivatives as anti-inflammatory agents.
AB  - Sepsis, a typically acute inflammatory disease, is the biggest cause of death in
      ICU (intensive care unit). Novel anti-inflammatory alternatives are still in
      urgent need. In this study, we designed and synthesized 30 indole-2-one and 7-aza
      2-oxindole derivatives based on the skeleton of tenidap, and their anti
      inflammatory activity was determined by evaluating the inhibitory potency against
      lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6 release in RAW264.7 macrophages. Quantitative SAR (structure
      activity relationship) analysis revealed that a high molecular polarizability and
      low lipid/water partition coefficient (ALogP) in indole-2-one are beneficial for
      anti-inflammatory activity. Moreover, compounds 7i and 8e inhibited the
      expression of TNF-alpha, IL-6, COX-2, PGES, and iNOS in LPS-stimulated
      macrophages, and 7i exhibited a significant protection from LPS-induced septic
      death in mouse models. These data present a series of new indole-2-one compounds
      with potential therapeutic effects in acute inflammatory diseases. 

PMID- 25378907
TI  - Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of
      Alzheimer's disease: design, synthesis, biochemical evaluation, ADMET, molecular
      modeling, and QSAR analysis of novel donepezil-pyridyl hybrids.
AB  - The design, synthesis, and biochemical evaluation of donepezil-pyridyl hybrids
      (DPHs) as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors
      for the potential treatment of Alzheimer's disease (AD) is reported. The 3D
      quantitative structure-activity relationship study was used to define 3D
      pharmacophores for inhibition of MAO A/B, acetylcholinesterase (AChE), and
      butyrylcholinesterase (BuChE) enzymes and to design DPHs as novel multi-target
      drug candidates with potential impact in the therapy of AD. DPH14 (Electrophorus
      electricus AChE [EeAChE]: half maximal inhibitory concentration [IC50] =1.1+/-0.3
      nM; equine butyrylcholinesterase [eqBuChE]: IC50 =600+/-80 nM) was 318-fold more
      potent for the inhibition of AChE, and 1.3-fold less potent for the inhibition of
      BuChE than the reference compound ASS234. DPH14 is a potent human recombinant
      BuChE (hBuChE) inhibitor, in the same range as DPH12 or DPH16, but 13.1-fold less
      potent than DPH15 for the inhibition of human recombinant AChE (hAChE). Compared
      with donepezil, DPH14 is almost equipotent for the inhibition of hAChE, and 8.8
      fold more potent for hBuChE. Concerning human monoamine oxidase (hMAO) A
      inhibition, only DPH9 and 5 proved active, compound DPH9 being the most potent
      (IC50 [MAO A] =5,700+/-2,100 nM). For hMAO B, only DPHs 13 and 14 were moderate
      inhibitors, and compound DPH14 was the most potent (IC50 [MAO B] =3,950+/-940
      nM). Molecular modeling of inhibitor DPH14 within EeAChE showed a binding mode
      with an extended conformation, interacting simultaneously with both catalytic and
      peripheral sites of EeAChE thanks to a linker of appropriate length. Absortion,
      distribution, metabolism, excretion and toxicity analysis showed that structures
      lacking phenyl-substituent show better druglikeness profiles; in particular,
      DPHs13-15 showed the most suitable absortion, distribution, metabolism, excretion
      and toxicity properties. Novel donepezil-pyridyl hybrid DPH14 is a potent,
      moderately selective hAChE and selective irreversible hMAO B inhibitor which
      might be considered as a promising compound for further development for the
      treatment of AD. 

PMID- 25378908
TI  - Intestinal absorption, organ distribution, and urinary excretion of the rare
      sugar D-psicose.
AB  - BACKGROUND: The purpose of this study was to evaluate intestinal absorption,
      organ distribution, and urinary elimination of the rare sugar D-psicose, a 3
      carbon stereoisomer of D-fructose that is currently being investigated and which
      has been found to be strongly effective against hyperglycemia and hyperlipidemia.
      METHODS: This study was performed using radioactive D-psicose, which was
      synthesized enzymatically from radioactive D-allose. Concentrations in whole
      blood, urine, and organs were measured at different time points until 2 hours
      after both oral and intravenous administrations and 7 days after a single oral
      administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also
      performed by injecting 100 mg/kg body weight of (14)C-labeled D-psicose or
      glucose intravenously to C3H mice. RESULTS: Following oral administration, D
      psicose easily moved to blood. The maximum blood concentration (48.5+/-15.6
      MUg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33%
      within 2 hours. Accumulation to organs was detected only in the liver. Following
      intravenous administration, blood concentration was decreased with the half
      life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour.
      Similarly to the results obtained with oral administration, accumulation to
      organs was detected only in the liver. Seven days after the single-dose oral
      administration, the remaining amounts in the whole body were less than 1%.
      Autoradiography of mice showed results similar to those in rats. High signals of
      (14)C-labeled D-psicose were observed in liver, kidney, and bladder.
      Interestingly, no accumulation of D-psicose was observed in the brain.
      CONCLUSION: D-psicose was absorbed well after oral administration and eliminated
      rapidly after both oral and intravenous administrations, with short duration of
      action. The study provides valuable pharmacokinetic data for further drug
      development of D-psicose. Because the findings were mainly based on animal study,
      it is necessary to implement human trials to study the metabolism pathway, which
      would give an important guide for human intake and food application of D-psicose.

PMID- 25378909
TI  - Anticancer efficacy and absorption, distribution, metabolism, and toxicity
      studies of aspergiolide A in early drug development.
AB  - Since the first anthracycline was discovered, many other related compounds have
      been studied in order to overcome its defects and improve efficacy. In the
      present paper, we investigated the anticancer effects of a new anthracycline,
      aspergiolide A (ASP-A), from a marine-derived fungus in vitro and in vivo, and we
      evaluated the absorption, distribution, metabolism, and toxicity drug properties
      in early drug development. We found that ASP-A had activity against topoisomerase
      II that was comparable to adriamycin. ASP-A decreased the growth of various human
      cancer cells in vitro and induced apoptosis in BEL-7402 cells via a caspase
      dependent pathway. The anticancer efficacy of ASP-A on the growth of
      hepatocellular carcinoma xenografts was further assessed in vivo. Results showed
      that, compared with the vehicle group, ASP-A exhibited significant anticancer
      activity with less loss of body weight. A pharmacokinetics and tissue
      distribution study revealed that ASP-A was rapidly cleared in a first order
      reaction kinetics manner, and was enriched in cancer tissue. The maximal
      tolerable dose (MTD) of ASP-A was more than 400 mg/kg, and ASP-A was not
      considered to be potentially genotoxic or cardiotoxic, as no significant increase
      of micronucleus rates or inhibition of the hERG channel was seen. Finally, an
      uptake and transport assay of ASP-A was performed in monolayers of Caco-2 cells,
      and ASP-A was shown to be absorbed through the active transport pathway.
      Altogether, these results indicate that ASP-A has anticancer activity targeting
      topoisomerase II, with a similar structure and mechanism to adriamycin, but with
      much lower toxicity. Nonetheless, further molecular structure optimization is
      necessary. 

PMID- 25378910
TI  - Efficacy of short novel antimicrobial and anti-inflammatory peptides in a mouse
      model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection.
AB  - The therapeutic efficacy of two novel short antimicrobial and anti-inflammatory
      peptides (RR and RRIKA) was evaluated in a mouse model of staphylococcal skin
      infection. RR (2%) and RRIKA (2%) significantly reduced the bacterial counts and
      the levels of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, and
      interleukin (IL)-6, in methicillin-resistant Staphylococcus aureus USA 300-0114
      skin lesions. Furthermore, the combined therapy of RRIKA (1%) and lysostaphin
      (0.5%) had significantly higher antistaphylococcal and anti-inflammatory activity
      compared to monotherapy. This study supports the potential use of these peptides
      for topical treatment of methicillin-resistant Staphylococcus aureus skin
      infections. 

PMID- 25378911
TI  - Clinical efficacy of second-generation tyrosine kinase inhibitors in imatinib
      resistant gastrointestinal stromal tumors: a meta-analysis of recent clinical
      trials.
AB  - BACKGROUND: Primary and secondary resistance to imatinib, a selective receptor
      tyrosine kinase inhibitor (TKI), is a serious clinical problem in the control of
      advanced gastrointestinal stromal tumors (GIST). Here we report on a meta
      analysis we performed to evaluate the efficacy of second-generation TKIs in the
      treatment of patients with imatinib-resistant GIST. METHODS: Randomized
      controlled trials evaluating the clinical efficacy of second-generation TKIs were
      identified by searching PubMed and EMBASE from 2000 to February 2014. Outcomes
      subjected to analysis were progression-free survival and overall survival.
      Statistical analyses were performed using Review Manager version 5.1.0 (Cochrane
      Collaboration, Oxford, UK). Weighted hazard ratios (HR) with 95% confidence
      intervals (CIs) were calculated for the outcomes. Fixed-effects or random-effects
      models were used, depending on the degree of heterogeneity across the selected
      studies. RESULTS: Three randomized controlled trials were selected for meta
      analysis. Among imatinib-resistant or imatinib-intolerant patients, 541 received
      second-generation TKIs (sunitinib, nilotinib, or regorafenib) and 267 controls
      received placebo or best supportive care. Progression-free survival was
      significantly improved in the TKI-treated group (HR 0.38; 95% CI 0.24-0.59;
      P<0.0001). No statistically significant difference was detected in overall
      survival between the treatment group and the control group (HR 0.85; 95% CI 0.71
      1.03; P=0.09). In the subgroup of patients who were resistant or intolerant to
      both imatinib and sunitinib, TKI therapy (nilotinib or regorafenib) improved
      progression-free survival (HR 0.40; 95% CI 0.19-0.84; P=0.02) but not overall
      survival (HR 0.83; 95% CI 0.63-1.08; P=0.17). Regorafenib was shown to be
      effective in terms of progression-free survival across different subpopulations
      of patients who were resistant to both imatinib and sunitinib. CONCLUSION: Second
      generation TKIs (sunitinib, nilotinib, and regorafenib) are effective in
      improving progression-free survival but not overall survival in patients with
      GIST who are resistant or intolerant to imatinib or to imatinib and sunitinib.
      Regorafenib is promising as a third-line treatment option for patients with
      advanced GIST.

PMID- 25378912
TI  - Gastroprotective activity of Annona muricata leaves against ethanol-induced
      gastric injury in rats via Hsp70/Bax involvement.
AB  - The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and
      graviola, is a widely distributed plant in Central and South America and tropical
      countries. Leaves of A. muricata have been reported to possess antioxidant and
      anti-inflammatory activities. In this study, the gastroprotective effects of
      ethyl acetate extract of A. muricata leaves (EEAM) were investigated against
      ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in
      rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this
      plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five
      groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and
      with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological
      features showed the antiulcerogenic characterizations of EEAM. There was
      significant suppression on the ulcer lesion index of rats pretreated with EEAM,
      which was comparable to the omeprazole effect in the omeprazole control group.
      Oral administration of EEAM to rats caused a significant increase in the level of
      nitric oxide and antioxidant activities, including catalase, glutathione, and
      superoxide dismutase associated with attenuation in gastric acidity, and
      compensatory effect on the loss of gastric wall mucus. In addition, pretreatment
      of rats with EEAM caused significant reduction in the level of malondialdehyde,
      as a marker for oxidative stress, associated with an increase in prostaglandin E2
      activity. Immunohistochemical staining also demonstrated that EEAM induced the
      downregulation of Bax and upregulation of Hsp70 proteins after pretreatment.
      Collectively, the present results suggest that EEAM has a promising antiulcer
      potential, which could be attributed to its suppressive effect against oxidative
      damage and preservative effect toward gastric wall mucus. 

PMID- 25378914
TI  - Understanding of pictograms from the United States Pharmacopeia Dispensing
      Information (USP-DI) among elderly Brazilians.
AB  - OBJECTIVE: To assess the understanding and cultural acceptability of the United
      States Pharmacopeia Dispensing Information (USP-DI) in a group of elderly
      Brazilians. METHODS: The study participants were individuals between 60 and 90
      years old, of both sexes, with different levels of education and income. Fifteen
      of 81 pictograms from the USP-DI were presented to the elderly subjects,
      individually, without subtitles and in random order, so that the participants'
      understanding of the pictograms could be evaluated. RESULTS: The study included
      116 participants. Only one of the selected pictograms reached the comprehension
      criterion established by the International Organization for Standardization 3864.
      With regard to the relationship between understanding and sociodemographic
      characteristics, age, wage income, and level of education were all found to be
      significantly associated with participants' understanding of some of the
      pictograms. CONCLUSION: Most of the USP-DI pictograms evaluated were not well
      understood by the elderly Brazilians. This finding indicates that such pictograms
      need to be culturally adapted for the Brazilian context if they are to serve
      their purpose effectively in this country.

PMID- 25378913
TI  - The influence of goal-directed fluid therapy on the prognosis of elderly patients
      with hypertension and gastric cancer surgery.
AB  - PURPOSE: We aimed to investigate the influence of perioperative goal-directed
      fluid therapy (GDFT) on the prognosis of elderly patients with gastric cancer and
      hypertension. METHODS: Sixty elderly patients (>60 years old) with primary
      hypertension who received gastric cancer radical surgery and who were American
      Society of Anesthesiologists (ASA) class II or III were enrolled in the current
      study. Selected patients were divided randomly into two arms, comprising a
      conventional intraoperative fluid management arm (arm C, n=30) and a GDFT arm
      (arm G, n=30). Patients in arm C were infused with crystalloids or colloids
      according to the methods of Miller's Anesthesia (6th edition), while those in arm
      G were infused with 200 mL hydroxyethyl starch over 15 minutes under the
      FloTrac/Vigileo monitoring system, with stroke volume variation between 8% and
      13%. Hemodynamics and tissue perfusion laboratory indicators in patients were
      recorded continuously from 30 minutes before the operation to 24 hours after the
      operation. RESULTS: Compared with arm C, the average intraoperative intravenous
      infusion quantity in arm G was significantly reduced (2,732+/-488 mL versus
      3,135+/-346 mL, P<0.05), whereas average colloid fluid volume was significantly
      increased (1,235+/-360 mL versus 760+/-280 mL, P<0.05). In addition, there were
      more patients exhibiting intraoperatively and postoperatively stable hemodynamics
      and less patients with low blood pressure in arm G. Postoperative complications
      were less frequent, and the time of postoperative hospital stay shorter, in arm
      G. No significant differences were observed in mortality between the two arms.
      CONCLUSION: Our research showed that GDFT stabilized perioperative hemodynamics
      and reduced the occurrence of postoperative complications in elderly patients who
      underwent gastric cancer surgery.

PMID- 25378915
TI  - Helping patients make better decisions: how to apply behavioral economics in
      clinical practice.
AB  - Clinicians are committed to effectively educating patients and helping them to
      make sound decisions concerning their own health care. However, how do clinicians
      determine what is effective education? How do they present information clearly
      and in a manner that patients understand and can use to make informed decisions?
      Behavioral economics (BE) is a subfield of economics that can assist clinicians
      to better understand how individuals actually make decisions. BE research can
      help guide interactions with patients so that information is presented and
      discussed in a more deliberate and impactful way. We can be more effective
      providers of care when we understand the factors that influence how our patients
      make decisions, factors of which we may have been largely unaware. BE research
      that focuses on health care and medical decision making is becoming more widely
      known, and what has been reported suggests that BE interventions can be effective
      in the medical realm. The purpose of this article is to provide clinicians with
      an overview of BE decision science and derived practice strategies to promote
      more effective behavior change in patients. 

PMID- 25378916
TI  - Both deterioration and improvement in activities of daily living are related to
      falls: a 6-year follow-up of the general elderly population study Good Aging in
      Skane.
AB  - OBJECTIVES: To determine the relationship between long-term change in activities
      of daily living (ADL) and falls in the elderly and to identify characteristics of
      groups at risk for falls. METHODS: This was a 6-year, prospective cohort study
      using data from the Good Aging in Skane study in southern Sweden, involving 1,540
      elderly subjects, including the oldest-old (age, 60-93 years). The subjects were
      recruited from the general population. ADL was measured at a baseline and follow
      up assessment, using Sonn and Asberg's revised scale and the ADL staircase. Falls
      were recorded in a period of 6 months before the follow-up assessment. The
      association between falls and change in ADL was calculated using adjusted,
      multiple logistic regression analysis and presented in odds ratios (ORs).
      RESULTS: Thirteen percent of the study population reported one or several falls
      in the measured period. Over the course of 6 years, one in four participants
      changed their ADL status, and parts of this category had an increased risk for
      falls compared with those who stayed independent in ADL or who had no change in
      the ADL staircase. Groups with different characteristics had a prominent risk for
      falls: those with a reduction of two to eight steps in the ADL staircase (OR,
      4.05; 95% confidence interval [CI], 1.62-10.11) and those becoming independent
      from dependency in instrumental ADL (OR, 4.13; 95% CI, 1.89-9.00). The former
      group had advanced age with a greater burden of cognitive impairment, gait
      disability, arrhythmia, and fall risk medications. The latter group had a higher
      prevalence of ischemic heart disease and low walking speed. CONCLUSION: Both
      deterioration and improvement in ADL over the course of 6 years increased the
      risk for falls in a general elderly population. Interventional efforts may
      require different strategies, as groups with different characteristics were at
      risk. Those at risk with improved ADL function may have a history of sufficient
      burden of comorbidity combined with obtained mobility for exposure to a fall
      event.

PMID- 25378917
TI  - Comparison of activities of daily living after osteoporotic hip fracture surgery
      in patients admitted from home and from geriatric health service facilities.
AB  - With the population and proportion of the elderly increasing each year,
      difficulties with postoperative treatment outcomes after osteoporotic hip
      fracture are increasing. This study focused on activities of daily living (ADL)
      in patients who underwent surgery for hip fracture through an investigation of
      living arrangements, the presence of dementia, and other complications of aging.
      Information from 99 patients who lived either at home or in geriatric health
      service facilities was collected for this trial. Most patients were over 65 years
      of age and female, and about half of them had dementia. The postoperative ADL
      score (focusing on patients' walking ability) was significant for those living at
      home than for those living in facilities. In addition, patients with dementia
      were divided into the following two categories: an early-rising group, comprising
      patients who were able to use a wheelchair within 48 hours of their operation;
      and a late-rising group, who did not start using a wheelchair until more than 48
      hours after surgery. The ADL scores for the two groups were compared. Although
      the preoperative ADL scores were not significantly different between the two
      groups, postoperative ADL scores were significantly higher in the early-rising
      group than in the late-rising group, especially in patients who had undergone
      hemiarthroplasty. These data suggest that ADL in dementia patients following hip
      fracture depends on the surgical procedure performed and whether they are late or
      early risers after surgery. 

PMID- 25378918
TI  - Comparing the effectiveness of small-particle versus large-particle inhaled
      corticosteroid in COPD.
AB  - PURPOSE: Small airway changes and dysfunction contribute importantly to airway
      obstruction in chronic obstructive pulmonary disease (COPD), which is currently
      treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at
      Global initiative for Obstructive Lung Disease (GOLD) grades 2-4. This
      retrospective matched cohort analysis compared effectiveness of a representative
      small-particle ICS (extrafine beclomethasone) and larger-particle ICS
      (fluticasone) in primary care patients with COPD. PATIENTS AND METHODS: Smokers
      and ex-smokers with COPD >= 40 years old initiating or stepping-up their dose of
      extrafine beclomethasone or fluticasone were matched 1:1 for demographic
      characteristics, index prescription year, concomitant therapies, and disease
      severity during 1 baseline year. During 2 subsequent years, we evaluated
      treatment change and COPD exacerbations, defined as emergency
      care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for
      lower respiratory tract infection. RESULTS: Mean patient age was 67 years, 57%
      60% being male. For both initiation (n=334:334) and step-up (n=189:189) patients,
      exacerbation rates were comparable between extrafine beclomethasone and
      fluticasone cohorts during the 2 year outcome period. Odds of treatment stability
      (no exacerbation or treatment change) were significantly greater for patients
      initiating extrafine beclomethasone compared with fluticasone (adjusted odds
      ratio 2.50; 95% confidence interval, 1.32-4.73). Median ICS dose exposure during
      2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone
      than fluticasone cohorts (315 MUg/day versus 436 MUg/day for initiation, 438
      MUg/day versus 534 MUg/day for step-up patients). CONCLUSION: We observed that
      small-particle ICS at significantly lower doses had comparable effects on
      exacerbation rates as larger-particle ICS at higher doses, whereas initiation of
      small-particle ICS was associated with better odds of treatment stability during
      2-years' follow-up.

PMID- 25378919
TI  - How do COPD comorbidities affect ICU outcomes?
AB  - BACKGROUND AND AIM: Chronic obstructive pulmonary disease (COPD) patients with
      acute respiratory failure (ARF) frequently require admission to the intensive
      care unit (ICU) for application of mechanical ventilation (MV). We aimed to
      determine whether comorbidities and clinical variables present at ICU admission
      are predictive of ICU mortality. METHODS: A retrospective, observational cohort
      study was performed in a tertiary teaching hospital's respiratory ICU using data
      collected between January 2008 and December 2012. Previously diagnosed COPD
      patients who were admitted to the ICU with ARF were included. Patients'
      demographics, comorbidities, body mass index (BMI), ICU admission data,
      application of noninvasive and invasive MV (NIV and IMV, respectively), cause of
      ARF, length of ICU and hospital stay, and mortality were recorded from their
      files. Patients were grouped according to mortality (survival versus non
      survival), and all the variables were compared between the two groups. RESULTS:
      During the study period, a total of 1,013 COPD patients (749 male) with a mean
      age (standard deviation) of 70 +/- 10 years met the inclusion criteria.
      Comorbidities of the non-survival group (female/male, 40/131) were significantly
      higher compared with the survival group (female/male, 224/618): arrhythmia (24%
      vs 11%), hypertension (42% vs 34%), coronary artery disease (28% vs 11%), and
      depression (7% vs 3%) (P<0.001, P<0.035, P<0.001, and P<0.007, respectively).
      Logistic regression revealed the following mortality risk factors: need of IMV,
      BMI <20 kg/m(2), pneumonia, coronary artery disease, arrhythmia, hypertension,
      chronic hypoxia, and higher acute physiology and chronic health evaluation II
      (APACHE II) scores. The respective odds ratios, confidence intervals, and P
      values for each of these were as follows: 27.7, 15.7-49.0, P<0.001; 6.6, 3.5
      412.7, P<0.001; 5.1, 2.9-8.8, P<0.001; 2.9, 1.5-5.6, P<0.001; 2.7, 1.4-5.2,
      P<0.003; 2.6, 1.5-4.4, P<0.001; 2.2, 1.2-3.9, P<0.008; and 1.1, 1.03-1.11,
      P<0.001. CONCLUSION: Patients with severe COPD and cardiac comorbidities and
      cachexia should be closely monitored in ICU due to their high risk of ICU
      mortality.

PMID- 25378920
TI  - Optimizing nonpharmacological management following an acute exacerbation of
      chronic obstructive pulmonary disease.
AB  - Though the guidelines for the optimal management of chronic obstructive pulmonary
      disease (COPD) following an acute exacerbation (AE) are well established, issues
      associated with poor adherence to nonpharmacological interventions such as self
      management advice and pulmonary rehabilitation will impact on hospital
      readmission rates and health care costs. Systems developed for clinically stable
      patients with COPD may not be sufficient for those who are post-exacerbation. A
      redesign of the manner in which such interventions are delivered to patients
      following an AECOPD is necessary. Addressing two or more components of the
      chronic care model is effective in reducing health care utilization in patients
      with COPD, with self-management support contributing a key role. By refining self
      management support to incorporate the identification and treatment of
      psychological symptoms and by providing health care professionals adequate time
      and training to deliver respiratory-specific advice and self-management
      strategies, adherence to nonpharmacological therapies following an AE may be
      enhanced. Furthermore, following up patients in their own homes allows for the
      tailoring of advice and for the delivery of consistent health care messages which
      may enable knowledge to be retained. By refining the delivery of
      nonpharmacological therapies following an AECOPD according to components of the
      chronic care model, adherence may be improved, resulting in better disease
      management and possibly reducing health care utilization. 

PMID- 25378922
TI  - Toxicity assessment of repeated intravenous injections of arginine-glycine
      aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice.
AB  - BACKGROUND: Nanotechnology-based near-infrared quantum dots (NIR QDs) have many
      excellent optical properties, such as high fluorescence intensity, good
      fluorescence stability, and strong tissue-penetrating ability. Integrin
      alphavbeta3 is highly and specifically expressed in tumor angiogenic vessel
      endothelial cells of almost all carcinomas. Recent studies have shown that NIR
      QDs linked to peptides containing the arginine-glycine-aspartic acid (RGD)
      sequence (NIR QDs-RGD) can specifically target integrin alphavbeta3 expressed in
      endothelial cells of tumor angiogenic vessels in vivo, and they offer great
      potential for early cancer diagnosis, in vivo tumor imaging, and tumor
      individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been
      reported. This study was conducted to investigate the toxicity of NIR QDs-RGD
      when intravenously administered to mice singly and repeatedly at the dose
      required for successful tumor imaging in vivo. MATERIALS AND METHODS: A NIR QDs
      RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of
      800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously
      injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each
      injection). Phosphate-buffered saline solution was used as control. Fourteen days
      postinjection, toxicity tests were performed, including complete blood count
      (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and
      neutrophils) and serum biochemical analysis (total protein, albumin,
      albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood
      urea nitrogen). The coefficients of liver, spleen, kidney, and lung weight to
      body weight were measured, as well as their oxidation and antioxidation
      indicators, including superoxide dismutase, glutathione, and malondialdehyde. The
      organs were also examined histopathologically. RESULTS: After one or two
      intravenous injections of QD800-RGD, as compared with control, no significant
      differences were observed in the complete blood count; biochemical indicators of
      blood serum, organ coefficient, and oxidation and antioxidation indicators; and
      no cell necrosis or inflammation were seen in the liver, spleen, kidney, or lung
      through histopathological examination. CONCLUSION: Our data demonstrate that the
      single and repeated intravenous injection of QD800-RGD at a dose needed for
      successful tumor imaging in vivo is not toxic to mice. Our work lays a solid
      foundation for further biomedical applications of NIR QDs-RGD.

PMID- 25378921
TI  - Oxidative stress and free radicals in COPD--implications and relevance for
      treatment.
AB  - Oxidative stress occurs when free radicals and other reactive species overwhelm
      the availability of antioxidants. Reactive oxygen species (ROS), reactive
      nitrogen species, and their counterpart antioxidant agents are essential for
      physiological signaling and host defense, as well as for the evolution and
      persistence of inflammation. When their normal steady state is disturbed,
      imbalances between oxidants and antioxidants may provoke pathological reactions
      causing a range of nonrespiratory and respiratory diseases, particularly chronic
      obstructive pulmonary disease (COPD). In the respiratory system, ROS may be
      either exogenous from more or less inhalative gaseous or particulate agents such
      as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some
      occupational dusts, or endogenously generated in the context of defense
      mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS
      may also damage body tissues depending on the amount and duration of exposure and
      may further act as triggers for enzymatically generated ROS released from
      respiratory, immune, and inflammatory cells. This paper focuses on the general
      relevance of free radicals for the development and progression of both COPD and
      pulmonary emphysema as well as novel perspectives on therapeutic options.
      Unfortunately, current treatment options do not suffice to prevent chronic airway
      inflammation and are not yet able to substantially alter the course of COPD.
      Effective therapeutic antioxidant measures are urgently needed to control and
      mitigate local as well as systemic oxygen bursts in COPD and other respiratory
      diseases. In addition to current therapeutic prospects and aspects of genomic
      medicine, trending research topics in COPD are presented. 

PMID- 25378923
TI  - Chitosan-decorated selenium nanoparticles as protein carriers to improve the in
      vivo half-life of the peptide therapeutic BAY 55-9837 for type 2 diabetes
      mellitus.
AB  - PURPOSE: As a potential protein therapeutic for type 2 diabetes mellitus (T2DM),
      BAY 55-9837 is limited by poor stability and a very short half-life in vivo. The
      purpose of this study was to construct a novel nanostructured biomaterial by
      conjugating BAY 55-9837 to chitosan-decorated selenium nanoparticles (CS-SeNPs)
      to prolong the in vivo half-life of BAY 55-9837 by reducing its renal clearance
      rate. MATERIALS AND METHODS: BAY 55-9837-loaded CS-SeNPs (BAY-CS-SeNPs) were
      prepared, and their surface morphology, particle size, zeta potential, and
      structure were characterized. The stability, protein-loading rate, and in vitro
      release of BAY 55-9837 from CS-SeNPs were also quantified. Additionally, a
      sensitive high-performance liquid chromatography (HPLC) assay was developed for
      the quantification of BAY 55-9837 in mouse plasma. Thereafter, mice were injected
      via the tail vein with either BAY 55-9837 or BAY-CS-SeNPs, and the plasma
      concentration of BAY 55-9837 was determined via our validated HPLC method at
      different time intervals postinjection. Relevant in vivo pharmacokinetic
      parameters (half-life, area under the curve from time 0 to last sampling point,
      observed clearance) were then calculated and analyzed. RESULTS: BAY-CS-SeNPs were
      successfully synthesized, with diameters of approximately 200 nm. BAY-CS-SeNPs
      displayed good stability with a high protein-loading rate, and the release
      process of BAY 55-9837 from the CS-SeNPs lasted for over 70 hours, with the
      cumulative release reaching 78.9%. Moreover, the conjugation of CS-SeNPs to BAY
      55-9837 significantly reduced its renal clearance to a rate of 1.56 mL/h and
      extended its half-life to 20.81 hours. CONCLUSION: In summary, our work provides
      a simple method for reducing the renal clearance rate and extending the half-life
      of BAY 55-9837 in vivo by utilizing CS-SeNPs as nanocarriers.

PMID- 25378924
TI  - Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth
      with reduced myelosuppression toxicity.
AB  - Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid
      tumors; however, its toxicity and side effects limit its clinical efficacy.
      Herein, docetaxel-loaded solid lipid nanoparticles (DSNs) were developed to
      reduce systemic toxicity of docetaxel while still keeping its anticancer
      activity. To evaluate its anticancer activity and toxicity, and to understand the
      molecular mechanisms of DSNs, different cellular, molecular, and whole genome
      transcription analysis approaches were utilized. The DSNs showed lower
      cytotoxicity compared with the commercial formulation of docetaxel
      (Taxotere((r))) and induced more apoptosis at 24 hours after treatment in vitro.
      DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose
      dependent manner similar to Taxotere. They can also suppress tumor growth very
      effectively in a mice model with human xenograft breast cancer. Systemic analysis
      of gene expression profiles by microarray and subsequent verification experiments
      suggested that both DSNs and Taxotere regulate gene expression and gene function,
      including DNA replication, DNA damage response, cell proliferation, apoptosis,
      and cell cycle regulation. Some of these genes expressed differentially at the
      protein level although their messenger RNA expression level was similar under
      Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of
      Taxotere by greatly lowering myelosuppression toxicity to bone marrow cells from
      mice. Taken together, these results expound the antitumor efficacy and the
      potential working mechanisms of DSNs in its anticancer activity and toxicity,
      which provide a theoretical foundation to develop and apply a more efficient
      docetaxel formulation to treat cancer patients. 

PMID- 25378926
TI  - Gum arabic-coated radioactive gold nanoparticles cause no short-term local or
      systemic toxicity in the clinically relevant canine model of prostate cancer.
AB  - INTRODUCTION: Gum arabic-coated radioactive gold nanoparticles (GA-(198)AuNPs)
      offer several advantages over traditional brachytherapy in the treatment of
      prostate cancer, including homogenous dose distribution and higher dose-rate
      irradiation. Our objective was to determine the short-term safety profile of GA
      (198)AuNPs injected intralesionally. We proposed that a single treatment of GA
      (198)AuNPs would be safe with minimal-to-no evidence of systemic or local
      toxicity. METHODS: Nine dogs with spontaneously occurring prostatic cancer were
      treated. Injections were performed with ultrasound or computerized tomography
      guidance. Complete blood counts, chemistry panels, and urinalyses were performed
      at weekly intervals for 1 month and imaging was repeated 4 weeks postinjection.
      Planar scintigraphic images were obtained within 30 minutes of injection.
      RESULTS: No statistically significant difference was found in any hematologic or
      biochemical parameter studied, nor was any evidence of tumor swelling or
      abscessation found in eight dogs with repeat imaging; one dog died secondary to
      urethral obstruction 12 days following injection. At 30 minutes postinjection, an
      average of 53% of injected dose in seven dogs was retained in the prostate, with
      loss of remaining activity in the bladder and urethra; no systemic uptake was
      detected. CONCLUSION: GA-(198)AuNP therapy had no short-term toxicity in the
      treatment of prostatic cancer. While therapeutic agent was found in the prostate
      immediately following injection, some loss of agent was detected in the bladder
      and urethra. Localization of radioactivity within the prostate was lower than
      anticipated and likely due to normal vestigial prostatic ducts. Therefore,
      further study of retention, dosimetry, long-term toxicity, and efficacy of this
      treatment is warranted prior to Phase I trials in men.

PMID- 25378925
TI  - Enhancement of oral bioavailability of cyclosporine A: comparison of various
      nanoscale drug-delivery systems.
AB  - A variety of nanoscale delivery systems have been shown to enhance the oral
      absorption of poorly water-soluble and poorly permeable drugs. However, the
      performance of these systems has seldom been evaluated simultaneously. The aim of
      this study was to compare the bioavailability enhancement effect of lipid-based
      nanocarriers with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to
      highlight the importance of the lipid composition, with cyclosporine A (CyA) as a
      model drug. CyA-loaded PLGA NPs, nanostructured lipid carriers (NLCs), and self
      microemulsifying drug-delivery systems (SMEDDS) were prepared. The particle size
      of PLGA NPs (182.2 +/- 12.8 nm) was larger than that of NLCs (89.7 +/- 9.0 nm)
      and SMEDDS (26.9 +/- 1.9 nm). All vehicles are charged negatively. The entrapment
      efficiency of PLGA NPs and NLCs was 87.6%+/- 1.6% and 80.3%+/- 0.6%,
      respectively. In vitro release tests indicated that the cumulative release of CyA
      was lower than 4% from all vehicles, including Sandimmun Neoral((r)), according
      to the dialysis method. Both NLCs and SMEDDS showed high relative oral
      bioavailability, 111.8% and 73.6%, respectively, after oral gavage administration
      to beagle dogs, which was not statistically different from commercial Sandimmun
      Neoral((r)). However, PLGA NPs failed to achieve efficient absorption, with
      relative bioavailability of about 22.7%. It is concluded that lipid-based
      nanoscale drug-delivery systems are superior to polymeric NPs in enhancing oral
      bioavailability of poorly water-soluble and poorly permeable drugs.

PMID- 25378927
TI  - Controllably local gene delivery mediated by polyelectrolyte multilayer films
      assembled from gene-loaded nanopolymersomes and hyaluronic acid.
AB  - To explore a spatiotemporally controllable gene delivery system with high
      efficiency and safety, polyelectrolyte multilayer (PEM) films were constructed on
      titanium or quartz substrates via layer-by-layer self-assembly technique by using
      plasmid deoxyribonucleic acid-loaded lipopolysaccharide-amine nanopolymersomes
      (pNPs) as polycations and hyaluronic acid (HA) as polyanions. pNPs were chosen
      because they have high transfection efficiency (>95%) in mesenchymal stem cells
      (MSCs) and induce significant angiogenesis in zebrafish in conventional bolus
      transfection. The assembly process of PEM films was confirmed by analyses of
      quartz crystal microbalance with dissipation, X-ray photoelectron spectroscopy,
      infrared, contact angle, and zeta potential along with atomic force microscopy
      observation. Quartz crystal microbalance with dissipation analysis reveals that
      this film grows in an exponential mode, pNPs are the main contributor to the film
      mass, and the film mass can be modulated in a relatively wide range (1.0-29
      MUg/cm(2)) by adjusting the deposition layer number. Atomic force microscopy
      observation shows that the assembly leads to the formation of a patterned film
      with three-dimensional tree-like nanostructure, where the branches are composed
      of beaded chains (pNP beads are strung on HA molecular chains), and the
      incorporated pNPs keep structure intact. In vitro release experiment shows that
      plasmid deoxyribonucleic acid can be gradually released from films over 14 days,
      and the released plasmid deoxyribonucleic acid exists in a complex form. In vitro
      cell experiments demonstrate that PEM films can enhance the adhesion and
      proliferation of MSCs and efficiently transfect MSCs in situ in vitro for at
      least 4 days. Our results suggest that a (pNPs/HA)n system can mediate efficient
      transfection in stem cells in a spatially and temporally controllable pattern,
      highlighting its huge potential in local gene therapy. 

PMID- 25378928
TI  - Biological impact of superparamagnetic iron oxide nanoparticles for magnetic
      particle imaging of head and neck cancer cells.
AB  - BACKGROUND: As a tomographic imaging technology, magnetic particle imaging (MPI)
      allows high spatial resolution and sensitivity, and the possibility to create
      real-time images by determining the spatial distribution of magnetic particles.
      To ensure a prospective biosafe application of UL-D (University of Luebeck
      Dextran coated superparamagnetic nanoparticles), we evaluated the
      biocompatibility of superparamagnetic iron oxide nanoparticles (SPIONs), their
      impact on biological properties, and their cellular uptake using head and neck
      squamous cancer cells (HNSCCs). METHODS: SPIONs that met specific MPI
      requirements were synthesized as tracers. Labeling and uptake efficiency were
      analyzed by hematoxylin and eosin staining and magnetic particle spectrometry.
      Flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT) assays, and real-time cell analyzer assays were used to investigate
      apoptosis, proliferation, and the cytokine response of SPION-labeled cells. The
      production of reactive oxygen species (ROS) was determined using a fluorescent
      dye. Experimental results were compared to the contrast agent Resovist((r)), a
      standard agent used in MPI. RESULTS: UL-D nanoparticles and Resovist particles
      were taken up in vitro by HNSCCs via unspecific phagocytosis followed by
      cytosolic accumulation. To evaluate toxicity, flow cytometry analysis was
      performed; results showed that dose- and time-dependent administration of
      Resovist induced apoptosis whereas cell viability of UL-D-labeled cells was not
      altered. We observed decreased cell proliferation in response to increased SPION
      concentrations. An intracellular production of ROS could not be detected,
      suggesting that the particles did not cause oxidative stress. Tumor necrosis
      factor alpha (TNF-alpha) and interleukins IL-6, IL-8, and IL-1beta were measured
      to distinguish inflammatory responses. Only the primary tumor cell line labeled
      with >0.5 mM Resovist showed a significant increase in IL-1beta secretion.
      CONCLUSION: Our data suggest that UL-D SPIONs are a promising tracer material for
      use in innovative tumor cell analysis in MPI.

PMID- 25378929
TI  - Factors associated with adherence to medication among depressed patients from
      Saudi Arabia: a cross-sectional study.
AB  - BACKGROUND: Several studies have investigated the factors associated with
      adherence to antidepressants, with inconsistent conclusions. However, no similar
      study has investigated this issue among patients diagnosed with major depressive
      disorder in Saudi Arabia. The aim of this study is to explore patients' adherence
      to antidepressant medications, and the factors associated with adherence.
      METHODS: A non-experimental cross-sectional design was used to measure adherence
      to antidepressants among major depressive disorder patients, and the factors
      associated with adherence. The patients were recruited from the outpatient clinic
      at the Al-Amal Complex for Mental Health in Riyadh, Saudi Arabia, between August
      2013 and January 2014. Eligible participants met with one of the research
      coordinators for assessment of their adherence. Adherence was investigated
      indirectly by use of the Morisky Medication Adherence Scale, and patients'
      beliefs were assessed through the Beliefs about Medicine Questionnaire.
      Information about the severity of their depression, demographics, and other study
      variables were collected. RESULTS: A total of 403 patients met the inclusion
      criteria and participated in the study. Of those, 203 (50.37%) were females,
      while the remaining 200 (49.6%) were males. There was an average age of 39 years
      (standard deviation, +/-11 years). Half of the patients (52.9%) reported low
      adherence to their antidepressant medication, with statistically significant
      differences between the low adherence and high adherence scores relating to sex,
      age, and duration of illness. CONCLUSION: Low medication adherence is a common
      problem among major depressive disorder patients in Saudi Arabia. Medication
      taking behavior among depressed patients is influenced by several factors, mainly
      patients' beliefs regarding antidepressants. This study has improved the
      understanding of the factors associated with adherence to antidepressants.

PMID- 25378930
TI  - Post hoc analyses of the impact of previous medication on the efficacy of
      lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity
      disorder in a randomized, controlled trial.
AB  - BACKGROUND: Following the approval of lisdexamfetamine dimesylate (LDX) in
      several European countries for the treatment of attention-deficit/hyperactivity
      disorder (ADHD) in children and adolescents with an inadequate response to
      methylphenidate (MPH) treatment, the aim of the present analysis was to establish
      the response to LDX in subgroups of patients with different ADHD medication
      histories. METHODS: This was a post hoc subgroup analysis of data from a 7-week,
      European, double-blind, dose-optimized, Phase III study. Patients aged 6-17 years
      were randomized 1:1:1 to LDX, placebo, or osmotic-release oral system
      methylphenidate (OROS-MPH). OROS-MPH was included as a reference arm rather than
      as a direct comparator. Efficacy was assessed in patients categorized according
      to their ADHD medication history using the ADHD Rating Scale IV and Clinical
      Global Impressions-Improvement (CGI-I) scores. RESULTS: The difference between
      active drug and placebo in least-squares mean change from baseline to endpoint in
      ADHD Rating Scale IV total score (95% confidence interval) was similar between
      the overall study population (n=317; LDX, -18.6 [-21.5, -15.7]; OROS-MPH, -13.0 [
      15.9, -10.2]) and treatment-naive individuals (n=147; LDX, -15.1 [-19.4, -10.9];
      OROS-MPH, -12.7 [-16.8, -8.5]) or patients previously treated with any ADHD
      medication (n=170; LDX, -21.5 [-25.5, -17.6]; OROS-MPH, -14.2 [-18.1, -10.3]). In
      addition, similar proportions of patients receiving active treatment were
      categorized as improved based on CGI-I score (CGI-I of 1 or 2) in the overall
      study population and among treatment-naive individuals or patients previously
      treated with any ADHD medication. CONCLUSION: In these post hoc analyses, the
      response to LDX treatment, and to the reference treatment OROS-MPH, was similar
      to that observed for the overall study population in subgroups of patients
      categorized according to whether or not they had previously received ADHD
      medication.

PMID- 25378932
TI  - More than 9 years of continuous trastuzumab treatment in metastatic breast cancer
      without cardiac toxicity: a case report and literature review.
AB  - The main concern of long-term use of trastuzumab remains its association with
      potential cardiac side effects. Although these side effects are real, they are
      probably overemphasized. We report the case of a woman with metastatic breast
      cancer, who is currently in complete remission, and who received trastuzumab
      continuously for more than 9 years, without any significant cardiac toxicity. 

PMID- 25378931
TI  - Consumption of water containing over 3.5 mg of dissolved hydrogen could improve
      vascular endothelial function.
AB  - BACKGROUND: The redox imbalance between nitric oxide and superoxide generated in
      the endothelium is thought to play a pivotal role in the development of
      endothelial dysfunction. A third reactive oxygen species (ROS), H2O2, is known to
      have both beneficial and detrimental effects on the vasculature. Nonetheless, the
      influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and
      there is no direct evidence that the hydroxyl radical impairs endothelial
      function in conduit arteries. Molecular hydrogen (H2) neutralizes detrimental
      ROS, especially the hydroxyl radical. OBJECTIVES: To assess the influence of the
      hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant,
      H2, can be a useful modulator of blood vessel function. METHODS: The efficacy of
      water containing a high concentration of H2 was tested by measuring flow-mediated
      dilation (FMD) of the brachial artery (BA). The subjects were randomly divided
      into two groups: the high-H2 group, who drank high-H2 water containing 7 ppm H2
      (3.5 mg H2 in 500 mL water); and the placebo group. Endothelial function was
      evaluated by measuring the FMD of the BA. After measurement of diameter of the BA
      and FMD at baseline, volunteers drank the high-H2 water or placebo water
      immediately and with a 30-minute interval; FMD was compared to baseline. RESULTS:
      FMD increased in the high-H2 group (eight males; eight females) from 6.80%+/
      1.96% to 7.64%+/-1.68% (mean +/- standard deviation) and decreased from 8.07%+/
      2.41% to 6.87%+/-2.94% in the placebo group (ten males; eight females). The ratio
      to the baseline in the changes of FMD showed significant improvement (P<0.05) in
      the high-H2 group compared to the placebo group. CONCLUSION: H2 may protect the
      vasculature from shear stress-derived detrimental ROS, such as the hydroxyl
      radical, by maintaining the nitric oxide-mediated vasomotor response.

PMID- 25378933
TI  - B7-H3 expression in breast cancer and upregulation of VEGF through gene silence.
AB  - B7-H3, a novel member of the B7 family, was previously known as a regulatory
      ligand regulating T-cell-mediated immune response, and in recent years it was
      found to take a significant role in various cancers. In some tumor types, high
      expression of B7-H3 had been linked to a poor prognosis, whereas in other cancers
      the opposite effect had been observed. The precise role of B7-H3 in tumor
      immunity is unclear, and further investigations are needed. In the present study,
      we studied the expression of B7-H3 in the pathologic specimens of 221 patients
      treated for breast cancer by immunohistochemistry. Strong B7-H3 expression was
      found in cancer tissues from 80.55% patients, and B7-H3 expression had a negative
      relation with vascular endothelial growth factor (VEGF) expression, microvascular
      density for CD34, and tumor size. Furthermore, through lipopolysaccharide
      mediated delivery of stable short hairpin ribonucleic acid we observed that
      silencing of B7-H3 could increase the transcription and secreting of VEGF in
      breast cancer cell line MCF-7. In summary, the present study demonstrated that B7
      H3 suppressed tumor growth through inhibiting VEGF expression. These results
      increased knowledge of the nonimmunological role of B7-H3 protein and provided
      novel insights into great biological functions and a putative therapeutic target
      in breast cancer. 

PMID- 25378934
TI  - Ramucirumab: preclinical research and clinical development.
AB  - Ramucirumab (IMC-1121B, LY3009806), a fully humanized monoclonal antibody
      directed against the extracellular domain of vascular endothelial growth factor
      receptor 2 (VEGFR-2), is a new therapeutic option that selectively inhibits the
      human VEGFR-2 with a much greater affinity than its natural ligands. Based on the
      promising results of both preclinical and early clinical studies, ramucirumab has
      been tested in different tumor types either alone or in combination with
      chemotherapy. While it has recently been granted its first US Food and Drug
      Administration approval for use as a single agent in patients with advanced or
      metastatic gastric cancer or gastroesophageal junction carcinoma, its role for
      metastatic breast cancer or advanced non-small-cell lung cancer is still debated.
      The aims of this review are to recall and discuss the most significant
      preclinical and clinical studies that led to the development of ramucirumab and
      to present the results of the randomized clinical trials that have tested its
      efficacy in different malignancies, including gastric and lung cancer. 

PMID- 25378935
TI  - Gli3 silencing enhances cyclopamine suppressive effects on ovarian cancer.
AB  - Ovarian cancer is a leading gynecological malignancy associated with high
      mortality. Hedgehog signaling has been found to be important for cell
      proliferation and tumor growth for multiple cancers, including ovarian cancer.
      The present study showed that the drug cyclopamine, which blocks the hedgehog
      signaling pathway, could reduce cancer cell growth and proliferation and induce
      cell apoptosis. In addition, the silencing of the glioma-associated oncogene
      (Gli)3, a downstream component of the hedgehog signaling pathway, could further
      enhance the antitumor effects of cyclopamine. Our results suggest that Gli3 may
      act as resistance to cyclopamine's effect on tumor growth. The combined treatment
      of cyclopamine application and Gli3 silencing therapy, therefore, may provide
      novel directions for clinical management of ovarian cancer. 

PMID- 25378936
TI  - The effects of ponatinib, a multi-targeted tyrosine kinase inhibitor, against
      human U87 malignant glioblastoma cells.
AB  - Glioblastoma is one of the most common malignant tumors in the nervous system in
      both adult and pediatric patients. Studies suggest that abnormal activation of
      receptor tyrosine kinases contributes to pathological development of
      glioblastoma. However, current therapies targeting tyrosine kinase receptors have
      poor therapeutic outcomes. Here, we examined anticancer effects of ponatinib, a
      multi-targeted tyrosine kinase inhibitor, on glioblastoma cells both in the U87MG
      cell line and in the mouse xenograft model. We showed that ponatinib treatment
      reduced cell viability and induced cell apoptosis in a dose-dependent manner in
      U87MG cells. In addition, ponatinib suppressed migration and invasion of U87MG
      cells effectively. Furthermore, ponatinib-treated tumors showed an obvious
      reduction of tumor volume and an increase of apoptosis as compared with vehicle
      treated tumors in the mouse xenograft model. These findings support a potential
      application of ponatinib as a chemotherapeutic option against glioblastoma cells.

PMID- 25378937
TI  - Proapoptotic and antiinvasive activity of Rac1 small molecule inhibitors on
      malignant glioma cells.
AB  - Malignant gliomas are characterized by an intrinsic ability to invade diffusely
      throughout the normal brain tissue. This feature contributes mainly to the
      failure of existing therapies. Deregulation of small GTPases signaling, in
      particular Rac1 activity, plays a key role in the invasive phenotype of gliomas.
      Here we report the effect of ZINC69391, a specific Rac1 inhibitor developed by
      our group, on human glioma cell lines LN229 and U-87 MG. ZINC69391 is able to
      interfere with the interaction of Rac1 with Dock180, a relevant Rac1 activator in
      glioma invasion, and to reduce Rac1-GTP levels. The kinase Pak1, a downstream
      effector of Dock180-Rac1 signaling, was also downregulated upon ZINC69391
      treatment. ZINC69391 reduced cell proliferation, arrested cells in G1 phase, and
      triggered apoptosis in glioma cells. Importantly, ZINC69391 dramatically affected
      cell migration and invasion in vitro, interfering with actin cytoskeleton
      dynamics. We also evaluated the effect of analog 1A-116, a compound derived from
      ZINC69391 structure. 1A-116 showed an improved antiproliferative and antiinvasive
      activity on glioma cells. These findings encourage further preclinical testing in
      clinically relevant animal models. 

PMID- 25378938
TI  - Economic burden of asthma in Abu Dhabi: a retrospective study.
AB  - This study evaluates the direct costs of treating asthma in Abu Dhabi in the
      United Arab Emirates. Data was compiled for 2011 from health insurance claims
      covering all medical interventions or treatments coded as asthma. Costs were
      calculated from a health care perspective. The total direct cost of treating
      139,092 asthma patients was estimated to be United Arab Emirates Dirhams (AED)
      105 million (US$29 million), corresponding to around AED 750 per patient per
      annum. The total cost is principally generated by outpatient visits (>AED 85
      million; 81% of the total cost). Ten point four percent of patients had made an
      emergency room visit. The cost per visit seems to be higher during hospital
      admissions (AED 7,123) compared to outpatient visits and emergency room visits.
      The direct cost of asthma medications was around AED 33 million (31% of the total
      cost). The economic burden of asthma in Abu Dhabi is high and the number of
      emergency visits suggests that the disease is not optimally controlled. 

PMID- 25378939
TI  - Clinical response and hospital costs associated with the empirical use of
      vancomycin and linezolid for hospital-acquired pneumonia in a Chinese tertiary
      care hospital: a retrospective cohort study.
AB  - AIMS: To evaluate clinical outcomes and allocation of hospital costs associated
      with empirical use of vancomycin or linezolid for hospital-acquired pneumonia
      (HAP) in the People's Republic of China. METHODS: Hospital episodes including HAP
      treated by vancomycin or linezolid between 2008 and 2012 in a Chinese tertiary
      care hospital were retrospectively identified from hospital administrative
      databases. Propensity score methods created best-matched pairs for the
      antibiotics. The matched pairs were used for adjusted comparisons on clinical
      response and allocation of hospital costs. Multiple regression analyses adjusting
      residual imbalance after matching were performed to confirm adjusted comparisons.
      RESULTS: Sixty matched pairs were created. Adjusted comparisons between
      vancomycin and linezolid showed similar clinical response rates (clinical cure:
      30.0% versus 31.7%, respectively; P=0.847; treatment failure: 55.0% versus 45.0%,
      respectively; P=0.289) but a significantly lower in-hospital mortality rate for
      vancomycin (3.3% versus 18.3%, respectively; P=0.013). After further adjusting
      for the imbalanced variables between matched treatment groups, the risks of
      treatment failure associated with the two antibiotics were comparable (odds
      ratio: 1.139; P=0.308) and there was a nonsignificant trend of lower risk of in
      hospital mortality associated with vancomycin (odds ratio: 0.186; P=0.055). The
      total hospital costs associated with vancomycin had a nonsignificant trend of
      being lower, likely because of its significantly lower acquisition costs (median:
      RMB 2,880 versus RMB 8,194; P<0.001; 1 RMB =0.16 USD). CONCLUSION: In tertiary
      care hospitals in the People's Republic of China, empirical treatment of patients
      with HAP with vancomycin had a comparable treatment failure rate but likely had a
      lower in-hospital mortality rate when compared with linezolid. Vancomycin also
      costs significantly less for drug acquisition than linezolid when treating HAP
      empirically.

PMID- 25378940
TI  - Pain severity and the economic burden of neuropathic pain in the United States:
      BEAT Neuropathic Pain Observational Study.
AB  - BACKGROUND: As with many chronic conditions, patients with neuropathic pain (NeP)
      are high consumers of health care resources. However, limited literature exists
      on the economic burden of NeP, including its impact on productivity. The aim of
      this study was to characterize health care resource utilization, productivity,
      and costs associated with NeP by pain severity level in US adults. METHODS:
      Subjects (n=624) with painful diabetic peripheral neuropathy, human
      immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP,
      spinal cord injury with NeP, chronic low back pain with NeP, and small fiber
      neuropathy were recruited during routine office visits to US community-based
      general practitioners and specialists. Clinicians captured clinical
      characteristics, NeP-related medications, and health care resource utilization
      based on 6-month retrospective medical chart review. Subjects completed
      questionnaires on demographics, pain/symptoms, costs, and productivity. Brief
      Pain Inventory pain severity scores were used to classify subjects by mild,
      moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates)
      were estimated, and differences across pain severity groups were evaluated.
      RESULTS: In total, 624 subjects were recruited (mean age 55.5+/-13.7 years; 55.4%
      male), and 504/624 (80.8%) reported moderate or severe pain. Statistically
      significant differences were observed across pain severity levels for number of
      comorbidities, prescription medications, physician office visits, and lost
      productivity (all P<=0.0001). At all pain severity levels, indirect costs were
      the primary cost driver. After adjusting for demographic and clinical variables,
      total mean (95% confidence interval [CI]) annualized direct medical costs to
      payers, direct costs to subjects, and indirect costs per subject were US$6,016
      (95% CI 5,316-6,716), US$2,219 (95% CI 1,919-2,519), and US$19,000 (95% CI 17,197
      20,802), respectively, with significant differences across pain severity levels.
      CONCLUSION: Subjects with NeP, mainly those showing moderate or severe pain, had
      significant associations between pain severity and NeP-related health care
      resource utilization, productivity, and costs. The economic burden, particularly
      indirect costs, was highest among those with severe pain and higher than
      previously reported in studies of specific NeP conditions.

PMID- 25378941
TI  - Skin-whitening and skin-condition-improving effects of topical oxidized
      glutathione: a double-blind and placebo-controlled clinical trial in healthy
      women.
AB  - PURPOSE: Glutathione is a tripeptide consisting of cysteine, glycine, and
      glutamate and functions as a major antioxidant. It is synthesized endogenously in
      humans. Glutathione protects thiol protein groups from oxidation and is involved
      in cellular detoxification for maintenance of the cell environment. Reduced
      glutathione (GSH) has a skin-whitening effect in humans through its tyrosinase
      inhibitory activity, but in the case of oxidized glutathione (GSSG) this effect
      is unclear. We examined the skin-whitening and skin-condition effects of topical
      GSSG in healthy women. SUBJECTS AND METHODS: The subjects were 30 healthy adult
      women aged 30 to 50 years. The study design was a randomized, double-blind,
      matched-pair, placebo-controlled clinical trial. Subjects applied GSSG 2%
      (weight/weight [w/w]) lotion to one side of the face and a placebo lotion to the
      other side twice daily for 10 weeks. We objectively measured changes in melanin
      index values, moisture content of the stratum corneum, smoothness, wrinkle
      formation, and elasticity of the skin. The principal investigator and each
      subject also used subjective scores to investigate skin whitening, wrinkle
      reduction, and smoothness. Analysis of variance was used to evaluate differences
      between groups. RESULTS: The skin melanin index was significantly lower with GSSG
      treatment than with placebo from the early weeks after the start of the trial
      through to the end of the study period (at 10 weeks, P<0.001). In addition, in
      the latter half of the study period GSSG-treated sites had significant increases
      in moisture content of the stratum corneum, suppression of wrinkle formation, and
      improvement in skin smoothness. There were no marked adverse effects from GSSG
      application. CONCLUSION: Topical GSSG is safe and effectively whitens the skin
      and improves skin condition in healthy women.

PMID- 25378943
TI  - Optimal first-line and second-line treatments for metastatic renal cell
      carcinoma: current evidence.
AB  - Since 2005, an abundance of targeted agents has been approved for the treatment
      of metastatic renal cell carcinoma (mRCC), without any specification as to what
      may be the most optimal first-line and second-line sequence. Hence, our objective
      was to critically examine the evidence supporting the use of first-line and
      second-line agents in the management of mRCC. Our review suggests that in first
      line, sunitinib and pazopanib represent treatment options for patients with
      favorable or intermediate-risk features and clear cell histology. Unfortunately,
      the Phase III trial cannot conclusively prove the noninferiority of pazopanib
      relative to sunitinib. Hence, the use of sunitinib as first-line standard of care
      remains justified. Pazopanib represents an option for specific patients in whom
      sunitinib might not be tolerated. In patients with poor-risk features,
      temsirolimus represents the only option supported with level 1 evidence. Less
      optimal alternatives include sunitinib and bevacizumab combined with interferon,
      based on the minimal inclusion of poor-risk patients in pivotal Phase III studies
      of these two molecules. In patients with non-clear cell mRCC, the use of
      temsirolimus is supported by Phase III data, unlike for any other molecule. In
      second line, the options consist of everolimus and axitinib. However, the
      axitinib data are substantially more robust given the inclusion of more patients
      considered as true second-line, and validly justify the choice of axitinib over
      everolimus. Nonetheless, the Phase III trial of everolimus may be considered as
      level 1 evidence for use as third-line or subsequent lines of therapy. 

PMID- 25378942
TI  - Management of hyperhidrosis.
AB  - Primary hyperhidrosis (HH), a condition of sweating in excess of thermoregulatory
      requirements, affects nearly 3% of the US population and carries significant
      emotional and psychosocial implications. Unlike secondary HH, primary HH is not
      associated with an identifiable underlying pathology. Our limited understanding
      of the precise pathophysiologic mechanism for HH makes its treatment particularly
      frustrating. However, a wide array of interventions for the treatment of HH have
      been implemented throughout the world. Herein, we discuss the most extensively
      studied therapeutic options for primary HH, including systemic oxybutynin,
      botulinum toxin injections, skin excision, liposuction-curettage, and
      sympathotomy/sympathectomy. We conclude with a discussion of possible future
      therapies for HH, including the applications of laser, microwave, and ultrasound
      technologies. 

PMID- 25378944
TI  - Diagnosis and activity assessment of immunoglobulin A nephropathy: current
      perspectives on noninvasive testing with aberrantly glycosylated immunoglobulin A
      related biomarkers.
AB  - Immunoglobulin (Ig) A nephropathy (IgAN) is the most common form of glomerular
      disease worldwide and is associated with a poor prognosis. Thus, development of a
      curative treatment and strategies for early diagnosis and treatment are urgently
      needed. Pathological analysis of renal biopsy is the gold standard for the
      diagnosis and assessment of disease activity; however, immediate and frequent
      assessment based on biopsy specimens is difficult. Therefore, a simple and safe
      alternative is desirable. On the other hand, it is now widely accepted that multi
      hit steps, including production of aberrantly glycosylated serum IgA1 (first
      hit), and IgG or IgA autoantibodies that recognize glycan containing epitopes on
      glycosylated serum IgA1 (second hit) and their subsequent immune complex
      formation (third hit) and glomerular deposition (fourth hit), are required for
      continued progression of IgAN. Although the prognostic and predictive values of
      several markers have been discussed elsewhere, we recently developed a highly
      sensitive and specific diagnostic method by measuring serum levels of
      glycosylated serum IgA1 and related IgA immune complex. In addition, we confirmed
      a significant correlation between serum levels of these essential effector
      molecules and disease activity after treatment, suggesting that each can be
      considered as a practical surrogate marker of therapeutic effects in this slowly
      progressive disease. Such a noninvasive diagnostic and activity assessment method
      using these disease-oriented specific biomarkers may be useful in the early
      diagnosis of and intervention in IgAN, with appropriate indication for treatment,
      and thus aid in the future development and dissemination of specific and curative
      treatments. 

PMID- 25378946
TI  - Profiling and targeting HER2-positive breast cancer using trastuzumab emtansine.
AB  - PURPOSE: This article reviews the mechanism of action of trastuzumab emtansine (T
      DM1), existing clinical data relating to its use for human growth factor receptor
      2 (HER2)-positive breast cancer, potential pathways of resistance, and ongoing
      studies evaluating this novel agent. BACKGROUND: The development of HER2-targeted
      therapies has dramatically improved clinical outcomes for patients with any stage
      of HER2-positive breast cancer. Although the positive effect of these treatments
      cannot be overstated, treatment resistance develops in the vast majority of those
      diagnosed with stage IV HER2-positive breast cancer. Moreover, HER2-directed
      therapies are most effective when combined with cytotoxic chemotherapy. The need
      for chemotherapy leads to significant adverse effects and a clear decrease in
      quality of life for those dealing with a chronic incurable disease. T-DM1 is a
      recently developed, novel antibody-drug conjugate in which highly potent
      maytanisinoid chemotherapy is stably linked to the HER2-targeted monoclonal
      antibody, trastuzumab. RESULTS: Preclinical and phase 1-3 clinical data support
      the significant antitumor activity of T-DM1. Importantly, several randomized
      studies also now demonstrate its clear superiority in terms of tolerability
      compared with standard chemotherapy-containing regimens. Its role in the
      treatment of trastuzumab-resistant metastatic breast cancer has now been
      established on the basis of the results of two phase 3 randomized studies, EMILIA
      (An Open-label Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine + Lapatinib
      in Patients With HER2-positive Locally Advanced or Metastatic Breast Cancer) and
      TH3RESA (A Study of Trastuzumab Emtansine in Comparison With Treatment of
      Physician's Choice in Patients With HER2-positive Breast Cancer Who Have Received
      at Least Two Prior Regimens of HER2-directed Therapy). The most common toxicities
      seen with T-DM1 are thrombocytopenia and an elevation in liver transaminases.
      Significant cardiac toxicity has not been demonstrated. Both in vitro cell line
      based studies as well as exploratory analyses of archived tumor samples from the
      clinical trials are seeking to understand potential mechanisms of resistance to T
      DM1. Ongoing studies are also evaluating the use of T-DM1 in the first-line
      metastatic, neoadjuvant, and adjuvant settings, as well as in combination with
      other targeted therapies. CONCLUSION: T-DM1 represents the first successfully
      developed antibody drug conjugate for the treatment of HER2-positive advanced
      breast cancer.

PMID- 25378947
TI  - Use of the painDETECT tool in rheumatoid arthritis suggests neuropathic and
      sensitization components in pain reporting.
AB  - Rheumatoid arthritis (RA) is an inflammatory autoimmune condition typified by
      systemic inflammation targeted toward synovial joints. Inhibition of
      proinflammatory networks by disease-modifying antirheumatic drugs, eg,
      methotrexate and biologic therapies, including tumor necrosis factor-alpha
      inhibitors, often leads to suppression of disease activity observed at the
      clinical level. However, despite the era of widespread use of disease-modifying
      treatments, there remain significant groups of patients who continue to
      experience pain. Our study formulated a pain assessment tool in the arthritis
      clinic to assess feasibility of measurements including the visual analog scale
      (VAS) and painDETECT to assess multimodal features of pain in people with
      established RA (n=100). Clinical measures of disease activity (Disease Activity
      Score in 28 Joints [DAS28]) were also recorded. Our data showed that despite the
      majority of subjects on at least one disease-modifying agent, the majority of
      patients reported severe pain (54%) by VAS, despite well-controlled clinical
      disease, with mean DAS28 2.07+/-0.9. Using the painDETECT questionnaire, 67% of
      patients had unlikely neuropathic pain. A significant proportion of subjects
      (28%) had possible neuropathic pain and 5% had features of likely neuropathic
      pain by painDETECT scoring. We found a positive correlation between VAS and
      painDETECT (R (2)=0.757). Of note, the group who had likely or probable
      neuropathic pain also showed significantly increased pain reporting by VAS
      (P<0.01). Subjects who were clinically obese (body mass index >30) also had
      statistically higher proportions of pain reporting (VAS 89.0+/-0.7 mm) compared
      with subjects who had a normal body mass index (VAS 45.2+/-21.8 mm), P<0.05. Our
      findings suggest that multimodal features of pain perception exist in RA,
      including neuropathic and sensitization elements, perhaps explaining why a
      subgroup of people with RA continue to experience ongoing pain, despite their
      apparent suppression of inflammation. 

PMID- 25378945
TI  - Clinical significance of pharmacogenomic studies in tardive dyskinesia associated
      with patients with psychiatric disorders.
AB  - Pharmacogenomics is the study of the effects of genetic polymorphisms on
      medication pharmacokinetics and pharmacodynamics. It offers advantages in
      predicting drug efficacy and/or toxicity and has already changed clinical
      practice in many fields of medicine. Tardive dyskinesia (TD) is a movement
      disorder that rarely remits and poses significant social stigma and physical
      discomfort for the patient. Pharmacokinetic studies show an association between
      cytochrome P450 enzyme-determined poor metabolizer status and elevated serum
      antipsychotic and metabolite levels. However, few prospective studies have shown
      this to correlate with the occurrence of TD. Many retrospective, case-control and
      cross-sectional studies have examined the association of cytochrome P450 enzyme,
      dopamine (receptor, metabolizer and transporter), serotonin (receptor and
      transporter), and oxidative stress enzyme gene polymorphisms with the occurrence
      and severity of TD. These studies have produced conflicting and confusing results
      secondary to heterogeneous inclusion criteria and other patient characteristics
      that also act as confounding factors. This paper aims to review and summarize the
      pharmacogenetic findings in antipsychotic-associated TD and assess its clinical
      significance for psychiatry patients. In addition, we hope to provide insight
      into areas that need further research. 

PMID- 25378949
TI  - Assessment of HER2 testing patterns, HER2+ disease, and the utilization of HER2
      directed therapy in early breast cancer.
AB  - CONTEXT: Determining human epidermal growth factor receptor 2 (HER2) status is
      critical for the management of early-stage breast cancer (ESBC). An understanding
      of HER2 testing practices can provide insight into how test results influence the
      use of HER2-directed therapy. OBJECTIVE: To assess HER2 testing, HER2+ disease,
      and HER2-directed therapy in ESBC at the Huntsman Cancer Institute before and
      after the 2007 American Society of Clinical Oncology and College of American
      Pathologist (ASCO/CAP) guidelines on HER2 testing were published. METHODS:
      Patients were identified from an institutional tumor registry. HER2 testing
      patterns and results were examined using a chart review of pathology and clinical
      notes. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated
      descriptively. Discordance rate with reflex testing (immunohistochemistry [IHC]2+
      retested by fluorescence in situ hybridization [FISH]) was also evaluated.
      RESULTS: A total of 1,459 women were included (mean age: 57 years). The rate of
      HER2+ disease was 17% (number [N] =245). The discordance rate between IHC2+ and
      FISH was 10%. After the 2007 ASCO/CAP guidelines, fewer tumors were classified as
      IHC3+ (16% post- versus 21.9% pre-2007), more tumors were characterized as IHC2+
      (26.4% post- versus 20.7% pre-2007), and the overall HER2+ rate was decreased
      (18.7% versus 21.9%), but this was not statistically significant (P=0.519). Most
      patients with HER2+ ESBC received HER2-targeted therapy (N=185). CONCLUSION: The
      HER2+ rate was 17% and within the range of the reported rates in the literature.
      Reflex testing identified additional HER2+ tumors by approximately 10%, and
      should be considered a potential quality indicator. ASCO/CAP HER2 testing
      guidelines in 2007 appeared to impact the interpretation and classification of
      HER2+ tumors.

PMID- 25378948
TI  - Toward a systematic approach to opioid rotation.
AB  - Patients requiring chronic opioid therapy may not respond to or tolerate the
      first opioid prescribed to them, necessitating rotation to another opioid. They
      may also require dose increases for a number of reasons, including worsening
      disease and increased pain. Dose escalation to restore analgesia using the
      primary opioid may lead to increased adverse events. In these patients, rotation
      to a different opioid at a lower-than-equivalent dose may be sufficient to
      maintain adequate tolerability and analgesia. In published trials and case
      series, opioid rotation is performed either using a predetermined substitute
      opioid with fixed conversion methods, or in a manner that appears to be no more
      systematic than trial and error. In clinical practice, opioid rotation must be
      performed with consideration of individual patient characteristics, comorbidities
      (eg, concurrent psychiatric, pulmonary, renal, or hepatic illness), and
      concurrent medications, using flexible dosing protocols that take into account
      incomplete opioid cross-tolerance. References cited in this review were
      identified via a search of PubMed covering all English language publications up
      to May 21, 2013 pertaining to opioid rotation, excluding narrative reviews,
      letters, and expert opinion. The search yielded a total of 129 articles, 92 of
      which were judged to provide relevant information and subsequently included in
      this review. Through a review of this literature and from the authors' empiric
      experience, this review provides practical information on performing opioid
      rotation in clinical practice. 

PMID- 25378950
TI  - Preventative therapies for healthy women at high risk of breast cancer.
AB  - Tamoxifen has been shown to reduce the risk of developing estrogen receptor (ER)
      positive breast cancer by at least 50%, in both pre- and postmenopausal women.
      The current challenge is to find new agents with fewer side effects and to find
      agents that are specifically suitable for premenopausal women with ER-negative
      breast cancer. Other selective estrogen receptor modulators (SERMs), such as
      raloxifene, arzoxifene, and lasofoxifene, have been shown to reduce the incidence
      of breast cancer by 50%-80%. SERMs are interesting agents for the prevention of
      breast cancer, but longer follow-up is needed for some of them for a complete
      risk-benefit profile of these drugs. Aromatase inhibitors have emerged as new
      drugs in the prevention setting for postmenopausal women. In the Mammary
      Prevention 3 (MAP3) trial, a 65% reduction in invasive breast cancer with
      exemestane was observed, and the Breast Cancer Intervention Study-II trial, which
      compared anastrozole with placebo, reported a 60% reduction in those cancers.
      Although SERMs and aromatase inhibitors have been proven to be excellent agents
      in the preventive setting specifically for postmenopausal women and ER-positive
      breast cancer, newer agents have to be found specifically for ER-negative breast
      cancers, which mostly occur in premenopausal women. 

PMID- 25378951
TI  - Systemic AA amyloidosis: epidemiology, diagnosis, and management.
AB  - The term "amyloidosis" encompasses the heterogeneous group of diseases caused by
      the extracellular deposition of autologous fibrillar proteins. The global
      incidence of amyloidosis is estimated at five to nine cases per million patient
      years. While amyloid light-chain (AL) amyloidosis is more frequent in developed
      countries, amyloid A (AA) amyloidosis is more common in some European regions and
      in developing countries. The spectrum of AA amyloidosis has changed in recent
      decades owing to: an increase in the median age at diagnosis; a percent increase
      in the frequency of primary AL amyloidosis with respect to the AA type; and a
      substantial change in the epidemiology of the underlying diseases. Diagnosis of
      amyloidosis is based on clinical organ involvement and histological evidence of
      amyloid deposits. Among the many tinctorial characteristics of amyloid deposits,
      avidity for Congo red and metachromatic birefringence under unidirectional
      polarized light remain the gold standard. Once the initial diagnosis has been
      made, the amyloid subtype must be identified and systemic organ involvement
      evaluated. In this sense, the (123)I-labeled serum amyloid P component
      scintigraphy is a safe and noninvasive technique that has revolutionized the
      diagnosis and monitoring of treatment in systemic amyloidosis. It can
      successfully identify anatomical patterns of amyloid deposition throughout the
      body and enables not only an initial estimation of prognosis, but also the
      monitoring of the course of the disease and the response to treatment. Given the
      etiologic diversity of AA amyloidosis, common therapeutic strategies are scarce.
      All treatment options should be based upon a greater control of the underlying
      disease, adequate organ support, and treatment of symptoms. Nevertheless, novel
      therapeutic strategies targeting the formation of amyloid fibrils and amyloid
      deposition may generate new expectations for patients with AA amyloidosis. 

PMID- 25378952
TI  - Factors influencing repair of dental restorations with resin composite.
AB  - The presentation of patients with dental restorations that exhibit minor defects
      is one of the commonest clinical situations in the practice of general dentistry.
      The repair of such restorations, rather than replacement, is increasingly
      considered to be a viable alternative to replacement of the defective
      restoration. This paper considers factors influencing the repair of direct
      restorations, including indications and details of relevant techniques, based on
      the best available knowledge and understanding of this important aspect of
      minimal intervention dentistry. Practitioners who do not consider repair before
      deciding to replace restorations that present with limited defects are encouraged
      to consider including repair in the treatment options in such situations. The
      effective repair of direct restorations can greatly influence the rate of descent
      down the "restorative death spiral". 

PMID- 25378953
TI  - Topical steroid addiction in atopic dermatitis.
AB  - The American Academy of Dermatology published a new guideline regarding topical
      therapy in atopic dermatitis in May 2014. Although topical steroid addiction or
      red burning skin syndrome had been mentioned as possible side effects of topical
      steroids in a 2006 review article in the Journal of the American Academy of
      Dermatology, no statement was made regarding this illness in the new guidelines.
      This suggests that there are still controversies regarding this illness. Here, we
      describe the clinical features of topical steroid addiction or red burning skin
      syndrome, based on the treatment of many cases of the illness. Because there have
      been few articles in the medical literature regarding this illness, the
      description in this article will be of some benefit to better understand the
      illness and to spur discussion regarding topical steroid addiction or red burning
      skin syndrome. 

PMID- 25378954
TI  - Patient perceptions on the subject of medical research.
AB  - While performing medical research we often spend little time addressing patient's
      views on how research participants perceive the trial will affect their own
      condition. This manuscript identifies various ways in which the field of medicine
      must approach the important subject of patient's outlook. The described approach
      is vital to succeed at achieving meaningful patient's involvement in research. 

PMID- 25378955
TI  - Prevalence and perinatal mortality associated with preterm births in a tertiary
      medical center in South East Nigeria.
AB  - BACKGROUND: Preterm birth is a high risk condition associated with significant
      mortality and morbidity in the perinatal, neonatal, and childhood periods, and
      even in adulthood. Knowledge of the epidemiology of preterm births is necessary
      for planning appropriate maternal and fetal care. OBJECTIVE: The objective of
      this study was to determine the prevalence, pattern, and perinatal mortality
      associated with preterm births at the University of Nigeria Teaching Hospital,
      Enugu, South East Nigeria. METHODS: This was a review of prospectively collected
      routine delivery data involving preterm deliveries that occurred between 1
      January 2009 and 31 December 2013. Data analysis involved descriptive and
      inferential statistics at 95% level of confidence using SPSS version 17.0 for
      Windows. RESULTS: There were 3,760 live births over the 5-year study period out
      of which 636 were preterm births, giving a prevalence rate of 16.9%. Spontaneous
      preterm births occurred in approximately 57% of preterm births while provider
      initiated births occurred in 43%. The mean gestational age at preterm deliveries
      was 32.6+/-3.2 weeks while the mean birth weight was 2.0+/-0.8 kilograms.
      Approximately 89% of preterm births involved singleton pregnancies. Sixty-eight
      percent of preterm births were moderate to late preterm. The male:female ratio of
      preterm babies born during the period was 1.2:1. The adjusted perinatal mortality
      rate for preterm babies in the study center was 46.1% (236/512). The stillbirth
      rate for preterm babies was 22.0% (149/678) and the adjusted early neonatal death
      rate was 24.0% (87/363). CONCLUSION: The prevalence of preterm births and
      associated perinatal mortality were high which may be a reflection of suboptimal
      prenatal and newborn care. An urgent improvement in prenatal and newborn care is
      therefore needed in the study center in order to improve the capacity to prevent
      or abate preterm labor, and preterm premature rupture of membranes; and to reduce
      avoidable stillbirths. Further upgrading of personnel and facilities in the
      newborn special care unit is also required to minimize early neonatal deaths.

PMID- 25378956
TI  - Women's perspectives on termination service delivery in Vietnam: a cross
      sectional survey in three provinces.
AB  - OBJECTIVE: To explore the perspectives of abortion service users regarding
      termination methods and abortion service delivery in Vietnam. MATERIALS AND
      METHODS: Structured exit interviews were conducted between August and November
      2011 with women who underwent termination of pregnancy at 62 public health
      facilities in Hanoi, Khanh Hoa, and Ho Chi Minh City in Vietnam. All women
      presenting for termination during the study period were recruited to participate
      in the study. Following their abortion, women were asked about their perspectives
      on abortion service delivery and attributes of medical abortion (MA) versus
      manual vacuum aspiration (MVA). Multiple logistic regression was used to assess
      the association between current method uptake and each attribute. RESULTS: A
      total of 1,233 women were included in the survey: 541 (43.9%) from Hanoi, 163
      (13.2%) from Khanh Hoa, and 529 (42.9%) from Ho Chi Minh: 23.1% underwent MA;
      78.9% reported that women should be given a choice between MA and MVA; and 77.6%
      thought that abortion services were accessible. Among the 48% who responded,
      30.1% thought that MA should be made available at primary/secondary health care
      facilities. Among women who had previously undergone both methods, women who
      reported that MA "feels more natural" (like a menstrual regulation/period) were
      more likely to choose MA for their current abortion (odds ratio 2.15, 95%
      confidence interval 1.26-3.69). CONCLUSION: MA uptake is significantly lower than
      MVA uptake. Further insights to women's perceptions of MA in Vietnam could help
      improve abortion service delivery in the country.

PMID- 25378957
TI  - Use of a radio frequency shield during 1.5 and 3.0 Tesla magnetic resonance
      imaging: experimental evaluation.
AB  - Radiofrequency (RF) shields have been recently developed for the purpose of
      shielding portions of the patient's body during magnetic resonance imaging (MRI)
      examinations. We present an experimental evaluation of a commercially available
      RF shield in the MRI environment. All tests were performed on 1.5 T and 3.0 T
      clinical MRI scanners. The tests were repeated with and without the RF shield
      present in the bore, for comparison. Effects of the shield, placed within the
      scanner bore, on the RF fields generated by the scanner were measured directly
      using tuned pick-up coils. Attenuation, by as much as 35 dB, of RF field power
      was found inside the RF shield. These results were supported by temperature
      measurements of metallic leads placed inside the shield, in which no measurable
      RF heating was found. In addition, there was a small, simultaneous detectable
      increase (~1 dB) of RF power just outside the edges of the shield. For these
      particular scanners, the autocalibrated RF power levels were reduced for scan
      locations prescribed just outside the edges of the shield, which corresponded
      with estimations based on the pick-up coil measurements. Additionally, no
      significant heating during MRI scanning was observed on the shield surface. The
      impact of the RF shield on the RF fields inside the magnet bore is likely to be
      dependent on the particular model of the RF shield or the MRI scanner. These
      results suggest that the RF shield could be a valuable tool for clinical MRI
      practices. 

PMID- 25378959
TI  - People who perceive themselves as active cannot identify the intensity
      recommended by the international physical activity guidelines.
AB  - BACKGROUND: Many national and international organizations recommend that adults
      achieve at least 150 minutes of aerobic physical activity (PA) weekly, at a
      minimum moderate intensity to optimize health benefits. It is unknown if people
      who consider themselves as active have the ability to identify what is considered
      moderate intensity. METHODS: Fifty-one participants who reported achieving a
      minimum 150 minutes per week at a minimum of moderate intensity PA were recruited
      through a local fitness facility. All participants underwent a single assessment
      involving questionnaires, clinical measures, and a treadmill test to measure the
      ability to perceive moderate intensity. Following the visit, participants' PA
      level was evaluated by heart rate monitor, while exercising, for 7 consecutive
      days. RESULTS: Eighty percent of participants overestimated moderate intensity on
      the treadmill test; they were at vigorous intensity compared to what is
      considered moderate. Only 11.8% of participants accurately identified moderate
      intensity; all of them were women (P=0.03), had a high level of education
      (P=0.04), and knew that moderate intensity was the minimum intensity recommended
      by health organizations (P<0.01). Only 69.2% of participants reached the aerobic
      component of the International Physical Activity Guidelines with no significant
      advantage for those correctly identifying moderate intensity. CONCLUSION: Most
      people who perceive themselves as active are exercising at vigorous intensity
      while believing they are at moderate intensity. In addition, in this active
      sample, one-third of the participants were not reaching the aerobic component of
      the International Physical Activity Guidelines.

PMID- 25378958
TI  - Surgical treatment of nonalcoholic fatty liver disease in severely obese
      patients.
AB  - Obesity is a multi-organ system disease with underlying metabolic abnormalities
      and chronic systemic inflammation. Nonalcoholic fatty liver disease (NAFLD) is a
      hepatic manifestation of obesity metabolic dysfunction and its associated
      cardiovascular- and liver-related morbidities and mortality. Our current
      understanding of NAFLD pathogenesis, disease characteristics, the role of insulin
      resistance, chronic inflammation, gut-liver and gut-brain crosstalk and the
      effectiveness of pharmacotherapy is still evolving. Bariatric surgery
      significantly improves metabolic and NAFLD histology in severely obese patients,
      although its positive effects on fibrosis are not universal. Bariatric surgery
      benefits NAFLD through its metabolic effect on insulin resistance, inflammation,
      and insulinotropic and anorexinogenic gastrointestinal hormones. Further studies
      are needed to understand the natural course of NAFLD in severely obese patients
      and the role of weight loss surgery as a primary treatment for NAFLD. 

PMID- 25378960
TI  - Effects of a high-intensity intermittent training program on aerobic capacity and
      lipid profile in trained subjects.
AB  - BACKGROUND: Data regarding the effect of training on plasma lipids are
      controversial. Most studies have addressed continuous or long intermittent
      training programs. The present study evaluated the effect of short-short high
      intensity intermittent training (HIIT) on aerobic capacity and plasma lipids in
      soccer players. METHODS: The study included 24 male subjects aged 21-26 years,
      divided into three groups: experimental group 1 (EG1, n=8) comprising soccer
      players who exercised in addition to regular short-short HIIT twice a week for 12
      weeks; experimental group 2 (EG2, n=8) comprising soccer players who exercised in
      a regular football training program; and a control group (CG, n=8) comprising
      untrained subjects who did not practice regular physical activity. Maximal
      aerobic velocity and maximal oxygen uptake along with plasma lipids were measured
      before and after 6 weeks and 12 weeks of the respective training program.
      RESULTS: Compared with basal values, maximal oxygen uptake had significantly
      increased in EG1 (from 53.3+/-4.0 mL/min/kg to 54.8+/-3.0 mL/min/kg at 6 weeks
      [P<0.05] and to 57.0+/-3.2 mL/min/kg at 12 weeks [P<0.001]). Maximal oxygen
      uptake was increased only after 12 weeks in EG2 (from 52.8+/-2.7 mL/min/kg to
      54.2+/-2.6 mL/min/kg, [P<0.05]), but remain unchanged in CG. After 12 weeks of
      training, maximal oxygen uptake was significantly higher in EG1 than in EG2
      (P<0.05). During training, no significant changes in plasma lipids occurred.
      However, after 12 weeks, total and low-density lipoprotein cholesterol levels had
      decreased (by about 2%) in EG1 but increased in CG. High-density lipoprotein
      cholesterol levels increased in EG1 and EG2, but decreased in CG. Plasma
      triglycerides decreased by 8% in EG1 and increased by about 4% in CG. CONCLUSION:
      Twelve weeks of short-short HIIT improves aerobic capacity. Although changes in
      the lipid profile were not significant after this training program, they may have
      a beneficial impact on health.

PMID- 25378961
TI  - Prognostic factors for death and survival with or without complications in
      cardiac arrest patients receiving CPR within 24 hours of anesthesia for emergency
      surgery.
AB  - PURPOSE: To determine prognostic factors for death and survival with or without
      complications in cardiac arrest patients who received cardiopulmonary
      resuscitation (CPR) within 24 hours of receiving anesthesia for emergency
      surgery. PATIENTS AND METHODS: A retrospective cohort study approved by the
      Maharaj Nakorn Chiang Mai University Hospital Ethical Committee. Data used were
      taken from records of 751 cardiac arrest patients who received their first CPR
      within 24 hours of anesthesia for emergency surgery between January 1, 2003 and
      October 31, 2011. The reviewed data included patient characteristics, surgical
      procedures, American Society of Anesthesiologist (ASA) physical status
      classification, anesthesia information, the timing of cardiac arrest, CPR
      details, and outcomes at 24 hours after CPR. Univariate and polytomous logistic
      regression analyses were used to determine prognostic factors associated with the
      outcome variable. P-values of less than 0.05 were considered statistically
      significant. RESULTS: The outcomes at 24 hours were death (638/751, 85.0%),
      survival with complications (73/751, 9.7%), and survival without complications
      (40/751, 5.3%). The prognostic factors associated with death were: age between 13
      34 years (OR =3.08, 95% CI =1.03-9.19); ASA physical status three and higher (OR
      =6.60, 95% CI =2.17-20.13); precardiopulmonary comorbidity (OR =3.28, 95% CI
      =1.09-9.90); the condition of patients who were on mechanical ventilation prior
      to receiving anesthesia (OR =4.11, 95% CI =1.17-14.38); surgery in the upper
      abdominal site (OR =14.64, 95% CI =2.83-75.82); shock prior to cardiac arrest (OR
      =6.24, 95% CI =2.53-15.36); nonshockable electrocardiography (EKG) rhythm (OR
      =5.67, 95% CI =1.93-16.62); cardiac arrest occurring in postoperative period (OR
      =7.35, 95% CI =2.89-18.74); and duration of CPR more than 30 minutes (OR =4.32,
      95% CI =1.39-13.45). The prognostic factors associated with survival with
      complications were being greater than or equal to 65 years of age (OR =4.30, 95%
      CI =1.13-16.42), upper abdominal site of surgery (OR =10.86, 95% CI =1.99-59.13),
      shock prior to cardiac arrest (OR =3.62, 95% CI =1.30-10.12), arrhythmia prior to
      cardiac arrest (OR =4.61, 95% CI =1.01-21.13), and cardiac arrest occurring in
      the postoperative period (OR =3.63, 95% CI =1.31-10.02). CONCLUSION: The
      mortality and morbidity in patients who received anesthesia for emergency surgery
      within 24 hours of their first CPR were high, and were associated with
      identifiable patient comorbidity, age, shock, anatomic site of operation, the
      timing of cardiac arrest, EKG rhythm, and the duration of CPR. EKG monitoring
      helps to identify cardiac arrest quickly and diagnose the EKG rhythm as a
      shockable or nonshockable rhythm, with CPR being performed as per the American
      Heart Association (AHA) CPR Guidelines 2010. The use of the fast track system in
      combination with an interdisciplinary team for surgery, CPR, and postoperative
      care helps to rescue patients in a short time.

PMID- 25378962
TI  - Longitudinal assessment of sleep disordered breathing in Vietnam veterans with
      post-traumatic stress disorder.
AB  - PURPOSE: Previous work has demonstrated the relatively high prevalence of risk
      factors for cognitive impairment, such as sleep disordered breathing (SDB) and
      obesity, in Vietnam War era veterans with post-traumatic stress disorder (PTSD).
      No data are currently available on the longitudinal stability of SDB as a risk
      factor for cognitive decline in that population, which this study now reports.
      METHODS: Sample consisted of 48 veterans of the Vietnam War with PTSD who
      completed longitudinal sleep assessments over a 3-year period. The primary
      outcome measure, the Apnea-Hypopnea Index (AHI) indicator, was determined during
      standard overnight polysomnography. Body mass index (BMI) was calculated using
      standard measurements. Measures of cognitive function tapped auditory verbal
      memory as measured by the Rey Auditory Verbal Learning Test and executive
      functioning as measured by the Color-Word Interference Test of the Delis-Kaplan
      Executive Function System battery. Statistical analyses included mixed effects
      modeling. RESULTS: In this sample, AHI increased significantly by 2.19 points per
      year (beta=2.19; P<0.005). AHI worsened over the 3-year period, increasing from a
      mean of 18.7+/-15.7 to 24.7+/-17.4 points. Neither BMI nor cognition showed
      significant change over the 3-year period. CONCLUSION: SDB worsened in a group of
      veterans of the Vietnam War with PTSD over a 3-year period. The worsening of SDB
      over time suggests the need for appropriate countermeasures in populations at
      risk for progression of the condition.

PMID- 25378963
TI  - The Ukrainian version of the pediatric Canadian acute respiratory illness and flu
      scale: a linguistic validation study.
AB  - BACKGROUND: There is no internationally recognized outcome measure for the
      assessment of acute respiratory tract infections (ARTIs) in children. The only
      identifiable scale initially developed for pediatric application has been the
      Canadian acute respiratory illness and flu scale (CARIFS). The aim of our trial
      was to adapt the English version of the CARIFS to the Ukrainian language.
      MATERIALS AND METHODS: We performed forward and backward translation of the
      original version of the CARIFS according to the recommended standard. Then, the
      final CARIFS-based Ukrainian questionnaires were given to 149 caregivers whose 3
      12 years old children suffered from ARTI. The questionnaires were completed twice
      by a caregiver 3-6 hours apart and once by a physician just after the second
      completion by a caregiver. The database was analyzed to assess the consistency
      (the Cronbach's alpha coefficient), sensitivity (the standardized response mean;
      the effect size), reliability (test-retest analysis), and validity (Pearson's
      correlation) of the CARIFS in the Ukrainian language. RESULTS: The backward
      translation of the Ukrainian version of the CARIFS demonstrated its good
      correspondence to the English version. The Cronbach's alpha coefficient was
      0.805, and item to total correlation coefficients varied from 0.185 to 0.665. The
      standardized response mean was 1.73, and the effect size was 2.50 suggesting good
      sensitivity of the scale. In the test-retest reliability analysis of 99
      questionnaires, the median CARIFS score for the first and the second measurement
      was 19.0 (interquartile range [IQR]: 14.5-25.0) and 19.0 (IQR: 15.0-25.0),
      respectively, with a median change of 0.0 (IQR: -1.0 to 0.0, P=0.996). The
      Pearson's correlation coefficient between the CARIFS score completed by a
      responder and a physician was 0.832 (P=0.004). CONCLUSION: The Ukrainian version
      of the CARIFS-based English questionnaire proved to be a consistent, sensitive,
      reliable, and valid instrument in the assessment of ARTI in preschool and
      elementary school children in the Ukrainian population.

PMID- 25378964
TI  - Optimal management of hemophilic arthropathy and hematomas.
AB  - Hemophilia is a hematological disorder characterized by a partial or complete
      deficiency of clotting factor VIII or IX. Its bleeding complications primarily
      affect the musculoskeletal system. Hemarthrosis is a major hemophilia-related
      complication, responsible for a particularly debilitating chronic arthropathy, in
      the long term. In addition to clotting factor concentrates, usually prescribed by
      the hematologist, managing acute hemarthrosis and chronic arthropathy requires a
      close collaboration between the orthopedic surgeon and physiotherapist. This
      collaboration, comprising a coagulation and musculoskeletal specialist, is key to
      effectively preventing hemarthrosis, managing acute joint bleeding episodes,
      assessing joint function, and actively treating chronic arthropathy. This paper
      reviews, from a practical point of view, the pathophysiology, clinical
      manifestations, and treatment of hemarthrosis and chronic hemophilia-induced
      arthropathy for hematologists, orthopedic surgeons, and physiotherapists. 

PMID- 25378965
TI  - Facilitating the development of professional identity through peer assisted
      learning in medical education.
AB  - Peer assisted learning (PAL) is well documented in the medical education
      literature. In this paper, the authors explored the role of PAL in a graduate
      entry medical program with respect to the development of professional identity.
      The paper draws on several publications of PAL from one medical school, but here
      uses the theoretical notion of legitimate peripheral participation in a medical
      school community of practice to shed light on learning through participation. As
      medical educators, the authors were particularly interested in the development of
      educational expertise in medical students, and the social constructs that
      facilitate this academic development. 

PMID- 25378966
TI  - Role of modern 3D echocardiography in valvular heart disease.
AB  - Three-dimensional (3D) echocardiography has been conceived as one of the most
      promising methods for the diagnosis of valvular heart disease, and recently has
      become an integral clinical tool thanks to the development of high quality real
      time transesophageal echocardiography (TEE). In particular, for mitral valve
      diseases, this new approach has proven to be the most unique, powerful, and
      convincing method for understanding the complicated anatomy of the mitral valve
      and its dynamism. The method has been useful for surgical management, including
      robotic mitral valve repair. Moreover, this method has become indispensable for
      nonsurgical mitral procedures such as edge to edge mitral repair and
      transcatheter closure of paravaluvular leaks. In addition, color Doppler 3D echo
      has been valuable to identify the location of the regurgitant orifice and the
      severity of the mitral regurgitation. For aortic and tricuspid valve diseases,
      this method may not be quite as valuable as for the mitral valve. However, the
      necessity of 3D echo is recognized for certain situations even for these valves,
      such as for evaluating the aortic annulus for transcatheter aortic valve
      implantation. It is now clear that this method, especially with the continued
      development of real-time 3D TEE technology, will enhance the diagnosis and
      management of patients with these valvular heart diseases. 

PMID- 25378967
TI  - The scientific achievements of the decades in Korean Acute Myocardial Infarction
      Registry.
AB  - The Korea Acute Myocardial Infarction Registry (KAMIR) was the first nationwide
      registry data collection designed to track outcomes of patients with acute
      myocardial infarction (AMI). These studies reflect the current therapeutic
      approaches and management for AMI in Korea. The results of KAMIR could help
      clinicians to predict the prognosis of their patients and identify better
      diagnostic and treatment tools to improve the quality of care. The KAMIR score
      was proposed to be a predictor of the prognosis of AMI patients. Triple
      antiplatelet therapy, consisting of aspirin, clopidogrel and cilostazol, was
      effective at preventing major adverse clinical outcomes. Drug-eluting stents were
      effective and safe in AMI patients with no increased risk of stent thrombosis.
      Statin therapy was effective in Korean AMI patients, including those with very
      low levels of low density cholesterol. The present review summarizes the 10-year
      scientific achievements of KAMIR from admission to outpatient care during long
      term clinical follow-up. 

PMID- 25378969
TI  - The long-term outcome of balloon dilation versus botulinum toxin injection in
      patients with primary achalasia.

PMID- 25378968
TI  - Recent advances in treatment of aplastic anemia.
AB  - Recent advances in the treatment of aplastic anemia (AA) made most of patients to
      expect to achieve a long-term survival. Allogeneic stem cell transplantation
      (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line
      treatment option for younger patients with severe or very severe AA, whereas
      immunosuppressive treatment (IST) is an alternative option for others. Horse anti
      thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST
      regimen with acceptable response rate. Recently, horse ATG had been not available
      and replaced with rabbit ATG in most countries. Subsequently, recent comparative
      studies showed that the outcomes of patients who received rabbit ATG/CsA were
      similar or inferior compared to those who received horse ATG/CsA. Therefore,
      further studies to improve the outcomes of IST, including additional eltrombopag,
      are necessary. On the other hand, the upper age limit of patients who are able to
      receive MSD-SCT as first-line treatment is a current issue because of favorable
      outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In
      addition, further studies to improve the outcomes of patients who receive
      allogeneic SCT from alternative donors are needed. In this review, current issues
      and the newly emerging trends that may improve their outcomes in near futures
      will be discussed focusing the management of patients with AA. 

PMID- 25378970
TI  - Appropriate candidates for statin use in heart failure.

PMID- 25378971
TI  - Changes in the epidemiology and burden of community-acquired pneumonia in Korea.

PMID- 25378972
TI  - Long-term outcomes of balloon dilation versus botulinum toxin injection in
      patients with primary achalasia.
AB  - BACKGROUND/AIMS: We compared the long-term outcomes of balloon dilation versus
      botulinum toxin injection in Korean patients with primary achalasia and
      identified factors predicting remission. METHODS: We included 73 patients with
      achalasia newly diagnosed between January 1988 and January 2011. We ultimately
      enrolled 37 of 55 patients with primary achalasia through telephone interviews,
      who were observed for over 1 year. Short-term outcomes were evaluated from the
      medical records based on symptom relief after 1 month of treatment. Long-term
      outcomes were evaluated in a telephone interview using a questionnaire. RESULTS:
      Twenty-five patients were administered a botulinum toxin injection and 12
      underwent balloon dilation. One month after the botulinum toxin injection,
      improvements were seen in chest pain (14 [56.0%] to 4 patients [16.0%]),
      regurgitation (16 [64.0%] to 4 [16.0%]), and dysphagia (25 [100.0%] to 5
      [20.0%]). In the balloon dilation group, chest pain (8 [66.7%] to 1 [8.3%]),
      regurgitation (11 [91.7%] to 1 [8.3%]), and dysphagia (12 [100.0%] to 1 [8.3%])
      had improved. A significant difference was observed in the mean remission
      duration between the botulinum toxin injection and balloon dilation groups (13
      months [range, 1 to 70] vs. 29 months [range, 6 to 72], respectively; p = 0.036).
      Independent factors predicting long-term remission included treatment type (odds
      ratio [OR], 6.982; p = 0.036) and the difference in the lower esophageal
      sphincter pressure (OR, 7.198; p = 0.012). CONCLUSIONS: Balloon dilation may be
      more efficacious than botulinum toxin for providing long-term remission in Korean
      patients with achalasia. Follow-up manometry may predict the long-term outcome.

PMID- 25378973
TI  - The diagnostic utility of chest computed tomography scoring for the assessment of
      amiodarone-induced pulmonary toxicity.
AB  - BACKGROUND/AIMS: Amiodarone is one of the most widely used antiarrhythmic agents;
      however, amiodarone-induced pulmonary toxicity (APT) can be irreversible and
      sometimes fatal. The aim of this study was to evaluate the feasibility of chest
      computed tomography (CT) as a diagnostic tool for APT and to assess the utility
      of the CT APT score as an index for predicting the severity of APT. METHODS:
      Patients underwent amiodarone treatment for various reasons, most often atrial
      fibrillation, for more than 2 years, and those that received a cumulative dose >
      100 g were enrolled. A total of 34 patients who underwent chest CT between
      December 2011 and June 2012 were enrolled, whether or not they had clinical
      symptoms. The APT CT score was defined as the number of involved regions in the
      lung, which was divided into 18 regions (right and left, upper, middle, and
      lower, and central, middle, and peripheral). The CT findings were evaluated
      according to the total dose and duration of amiodarone treatment and the results
      of a pulmonary function test. Clinical symptoms and outcomes were also evaluated
      according to APT CT scores. RESULTS: Seven patients had positive APT CT scores
      (interstitial fibrosis in five, organizing pneumonia in one, and mixed
      interstitial fibrosis and organizing pneumonia in one), and these patients
      exhibited significantly lower diffusion capacity for carbon monoxide in the lungs
      compared with patients without an increased APT CT score (70.2% +/- 6.9% vs.
      89.7% +/- 19.4%; p = 0.011). Three of the seven patients experienced overt APT
      that required hospital admission. CONCLUSIONS: Chest CT is a useful diagnostic
      tool for APT, and the APT CT score might be a useful index for assessing the
      severity of APT.

PMID- 25378974
TI  - Effects of intensive versus mild lipid lowering by statins in patients with
      ischemic congestive heart failure: Korean Pitavastatin Heart Failure (SAPHIRE)
      study.
AB  - BACKGROUND/AIMS: This study was designed to evaluate the dose-effect relationship
      of statins in patients with ischemic congestive heart failure (CHF), since the
      role of statins in CHF remains unclear. METHODS: The South koreAn Pitavastatin
      Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic
      CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin. RESULTS: The
      low density lipoprotein cholesterol level decreased by 30% in the pitavastatin
      group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular
      systolic dimensions decreased significantly by 9% in the pitavastatin group and
      by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved
      significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in
      the pravastatin group. Although the extent of the EF change was greater in the
      pitavastatin group (16% vs. 11%) than that in the pravastatin group, no
      significant difference was observed between the groups (p = 0.386). Exercise
      capacity, evaluated by the 6-min walking test, improved significantly in the
      pravastatin group (p < 0.001), but no change was observed in the pitavastatin
      group (p = 0.371). CONCLUSIONS: Very low dose/low potency pravastatin and high
      dose/high potency pitavastatin had a beneficial effect on cardiac reverse
      remodeling and improved systolic function in patients with ischemic CHF. However,
      only pravastatin significantly improved exercise capacity. These findings suggest
      that lowering cholesterol too much may not be beneficial for patients with CHF.

PMID- 25378975
TI  - Disease burden of pneumonia in Korean adults aged over 50 years stratified by age
      and underlying diseases.
AB  - BACKGROUND/AIMS: This study was conducted to assess the disease burden of
      pneumonia according to age and presence of underlying diseases in patients
      admitted with community-acquired pneumonia (CAP). METHODS: We performed a
      retrospective, observational study and collected data targeting patients with CAP
      (>= 50 years) from 11 hospitals. Disease burden was defined as total per-capita
      medical fee, severity (CURB-65), hospital length of stay (LOS), and mortality.
      RESULTS: Of the 693 enrolled subjects, elderly subjects (age, >= 65 years) had a
      higher mean CURB-65 score (1.56 vs. 0.25; p < 0.01) and higher mortality than
      nonelderly subjects (4.4% [n = 21] vs. 0.5% [n = 1]; p = 0.00). In addition, the
      total cost of pneumonia treatment was higher in elderly patients compared to in
      nonelderly patients (KRW 2,088,190 vs. US $1,701,386; p < 0.01). Those with an
      underlying disease had a higher CURB-65 score (1.26 vs. 0.68; p < 0.01), were
      much older (mean age, 71.24 years vs. 64.24 years; p < 0.01), and had a higher
      mortality rate than those without an underlying disease (3.5% [n = 20] vs. 1.7%
      [n = 2]; p = 0.56). Total per-capita medical fees were higher (KRW 2,074,520 vs.
      US $1,440,471; p < 0.01) and hospital LOS was longer (mean, 8.38 days vs. 6.42
      days; p < 0.01) in patients with underlying diseases compared to those without.
      CONCLUSIONS: Due to the relatively high disease burden in Korea, particularly in
      the elderly and in those with an underlying disease, closer and more careful
      observation is needed to improve the outcomes of patients with CAP.

PMID- 25378976
TI  - The impact of high-flux dialysis on mortality rates in incident and prevalent
      hemodialysis patients.
AB  - BACKGROUND/AIMS: The effect of high-flux (HF) dialysis on mortality rates could
      vary with the duration of dialysis. We evaluated the effects of HF dialysis on
      mortality rates in incident and prevalent hemodialysis (HD) patients. METHODS:
      Incident and prevalent HD patients were selected from the Clinical Research
      Center registry for end-stage renal disease (ESRD), a Korean prospective
      observational cohort study. Incident HD patients were defined as newly diagnosed
      ESRD patients initiating HD. Prevalent HD patients were defined as patients who
      had been receiving HD for > 3 months. The primary outcome measure was all-cause
      mortality. RESULTS: This study included 1,165 incident and 1,641 prevalent HD
      patients. Following a median 24 months of follow-up, the mortality rates of the
      HF and low-flux (LF) groups did not significantly differ in the incident patients
      (hazard ratio [HR], 1.046; 95% confidence interval [CI], 0.592 to 1.847; p =
      0.878). In the prevalent patients, HF dialysis was associated with decreased
      mortality compared with LF dialysis (HR, 0.606; 95% CI, 0.416 to 0.885; p =
      0.009). CONCLUSIONS: HF dialysis was associated with a decreased mortality rate
      in prevalent HD patients, but not in incident HD patients.

PMID- 25378977
TI  - Clinical significance of nuclear factor kappaB and chemokine receptor CXCR4
      expression in patients with diffuse large B-cell lymphoma who received rituximab
      based therapy.
AB  - BACKGROUND/AIMS: This study investigated the expression of nuclear factor kappaB
      (NF-kappaB) and the chemokine receptor (CXCR4) in patients with diffuse large B
      cell lymphoma (DLBCL) who received rituximab-based therapy. METHODS: Seventy
      patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and
      immunohistochemistry was performed to determine the expression of NF-kappaB
      (IkappaB kinase alpha, p50, and p100/p52) and CXCR4. To classify DLBCL cases as
      germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical
      expression of CD10, bcl-6, or MUM1 was used in this study. The expression was
      divided into two groups according to the intensity score (negative, 0 or 1+;
      positive, 2+ or 3+). RESULTS: The median age of the patients was 66 years (range,
      17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV
      disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or
      high-intermediate risk according to their International Prognostic Indexs (IPIs).
      The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF
      kappaB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-kappaB
      expression was associated with CXCR4 expression (p = 0.002), and 56 patients
      (80.0%) showed coexpression. However, the expression of NF-kappaB or CXCR4 was
      not associated with overall survival and EFS. On multivariate analysis that
      included age, gender, performance status, stage, and the IPI, no significant
      association between the grade of NF-kappaB or CXCR4 expression and survival was
      observed. CONCLUSIONS: The current study suggests that the tissue expression of
      NF-kappaB and CXCR4 may not be an independent prognostic marker in DLBCL patients
      treated with R-CHOP.

PMID- 25378978
TI  - Kinetics of T-cell-based assays on cerebrospinal fluid and peripheral blood
      mononuclear cells in patients with tuberculous meningitis.
AB  - BACKGROUND/AIMS: The goal of this study was to monitor tuberculosis (TB)-specific
      T-cell responses in cerebrospinal fluid-mononuclear cells (CSF-MCs) and
      peripheral blood mononuclear cells (PBMCs) in patients with tuberculous
      meningitis (TBM) over the course of anti-TB therapy. METHODS: Adult patients (>=
      16 years) with TBM admitted to Asan Medical Center, Seoul, South Korea, were
      prospectively enrolled between April 2008 and April 2011. Serial blood or CSF
      samples were collected over the course of the anti-TB therapy, and analyzed using
      an enzyme-linked immunosorbent spot (ELISPOT) assay. RESULTS: Serial ELISPOT
      assays were performed on PBMCs from 17 patients (seven definite, four probable,
      and six possible TBM) and CSF-MC from nine patients (all definite TBM). The
      median number of interferon-gamma (IFN-gamma)-producing T-cells steadily
      increased during the first 6 months after commencement of anti-TB therapy in
      PBMCs. Serial CSF-MC ELISPOT assays revealed significant variability in immune
      responses during the first 6 weeks of anti-TB therapy, though early increases in
      CSF-MC ELISPOT results were associated with treatment failure or paradoxical
      response. CONCLUSIONS: Serial analysis of PBMCs by ELISPOT during the course of
      treatment was ineffective for predicting clinical response. However, increases in
      TB-specific IFN-gamma-producing T-cells in CSF-MC during the early phase of anti
      TB therapy may be predictive of clinical failure.

PMID- 25378979
TI  - Clinical features of elderly chronic urticaria.
AB  - BACKGROUND/AIMS: Chronic urticaria (CU) is defined as itchy wheals lasting 6
      weeks or more. As the aged population increases worldwide, it is essential to
      identify the specific features of this disease in the elderly population.
      METHODS: We investigated the prevalence and clinical features of CU in elderly
      patients. Medical records of 837 CU patients from the outpatient Allergy Clinic
      of Ajou University Hospital, Korea were analyzed retrospectively. Patients with
      chronic spontaneous urticaria according to the EAACI/GA2LEN/EDF/WAO guidelines
      were included. Patients older than 60 years were defined as elderly. RESULTS: Of
      the 837 patients, 37 (4.5%) were elderly. In elderly versus nonelderly CU
      patients, the prevalence of atopic dermatitis (AD) was significantly higher
      (37.8% vs. 21.7%, respectively; p = 0.022), while that of aspirin intolerance was
      lower (18.9% vs. 43.6%, respectively; p = 0.003) in terms of comorbid conditions.
      The prevalences of serum specific immunoglobulin E antibodies to staphylococcal
      enterotoxin A and staphylococcal enterotoxin B were considerably higher in
      elderly CU patients with AD than in those without AD (37.5% vs. 0%,
      respectively). CONCLUSIONS: Elderly patients with CU had a higher prevalence of
      AD. Therefore, there is a need to recognize the existence of AD in elderly CU
      patients.

PMID- 25378980
TI  - Early effects of tumor necrosis factor inhibition on bone homeostasis after
      soluble tumor necrosis factor receptor use.
AB  - BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble
      tumor necrosis factor (TNF) receptor affects circulating markers of bone
      metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA
      patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and
      glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum
      levels of bone metabolism markers were compared among patients treated with
      DMARDs at baseline and after etanercept treatment, normal controls and naive RA
      patients not previously treated with DMARDs (both age- and gender-matched).
      RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)
      1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA
      patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin
      levels increased. In patients whose DAS28 improved, the sclerostin level
      increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was
      statistically significant (p = 0.021). Increases in sclerostin levels after
      etanercept treatment were positively correlated with those of serum CTX-1 (r =
      0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with
      DMARDs showed depressed bone metabolism compared to naive RA patients. Increases
      in serum CTX-1 and sclerostin levels after short-term etanercept treatment
      suggest reconstitution of bone metabolism homeostasis.

PMID- 25378981
TI  - Complex repetitive discharge on electromyography as a risk factor for malignancy
      in idiopathic inflammatory myopathy.
AB  - BACKGROUND/AIMS: We investigated the electromyography (EMG) findings and
      demographic, clinical, and laboratory features that may predict the development
      of malignancy in patients with idiopathic inflammatory myopathy (IIM). METHODS:
      In total, 61 patients, 36 with dermatomyositis and 25 with polymyositis, were
      included. Patients were divided into those with and without malignancies, and
      comparisons were made between the groups in terms of their demographic, clinical,
      laboratory, and EMG findings. RESULTS: The frequencies of malignancies associated
      with dermatomyositis and polymyositis were 22% and 8%, respectively. Patients
      with malignancies showed a significantly higher incidence of dysphagia (odds
      ratio [OR], 21.50; 95% confidence interval [CI], 3.84 to 120.49), absence of
      interstitial lung disease (ILD; OR, 0.12; 95% CI, 0.01 to 0.98), and complex
      repetitive discharge (CRD) on the EMG (OR, 26.25; 95% CI, 2.67 to 258.52), versus
      those without. After adjustment for age, dysphagia and CRD remained significant,
      while ILD showed a trend for a difference but was not statistically significant.
      Multivariate analysis revealed that the CRD conferred an OR of 25.99 (95% CI,
      1.27 to 531.86) for malignancy. When the frequency of malignancy was analyzed
      according to the number of risk factors, patients with three risk factors showed
      a significantly higher incidence of malignancy, versus those with fewer than two
      (p = 0.014). CONCLUSIONS: We demonstrated for the first time that CRD on the EMG
      was an additional independent risk factor for malignancy in IIM. Further studies
      on a larger scale are needed to confirm the importance of CRD as a risk factor
      for malignancy in IIM.

PMID- 25378982
TI  - Funtional significance of the intermediate lesion in a single coronary artery
      assessed by fractional flow reserve.

PMID- 25378983
TI  - Graves' disease presenting with acute renal infarction.

PMID- 25378984
TI  - Persistent suboptimal molecular response in a patient with chronic myelogenous
      leukemia and Klinefelter syndrome.

PMID- 25378985
TI  - Transformation into large-cell neuroendocrine carcinoma associated with acquired
      resistance to erlotinib in nonsmall cell lung cancer.

PMID- 25378986
TI  - Parvimonas micra chest wall abscess following transthoracic lung needle biopsy.

PMID- 25378987
TI  - Crystals in a patient with asymptomatic proteinuria.

PMID- 25378988
TI  - Fibromuscular dysplasia: a cause of secondary hypertension.

PMID- 25378989
TI  - A review on the medicinal potentials of ginseng and ginsenosides on
      cardiovascular diseases.
AB  - Ginseng is widely used for its promising healing and restorative properties as
      well as for its possible tonic effect in traditional medicine. Nowadays, many
      studies focus on purified individual ginsenoside, an important constituent in
      ginseng, and study its specific mechanism of action instead of whole-plant
      extracts on cardiovascular diseases (CVDs). Of the various ginsenosides, purified
      ginsenosides such as Rb1, Rg1, Rg3, Rh1, Re, and Rd are the most frequently
      studied. Although there are many reports on the molecular mechanisms and medical
      applications of ginsenosides in the treatment of CVDs, many concerns exist in
      their application. This review discusses current works on the countless
      pharmacological functions and the potential benefits of ginseng in the area of
      CVDs. RESULTS: Both in vitro and in vivo results indicate that ginseng has
      potentially positive effects on heart disease through its various properties
      including antioxidation, reduced platelet adhesion, vasomotor regulation,
      improving lipid profiles, and influencing various ion channels. To date,
      approximately 40 ginsenosides have been identified, and each has a different
      mechanism of action owing to the differences in chemical structure. This review
      aims to present comprehensive information on the traditional uses,
      phytochemistry, and pharmacology of ginseng, especially in the control of
      hypertension and cardiovascular function. In addition, the review also provides
      an insight into the opportunities for future research and development on the
      biological activities of ginseng.

PMID- 25378990
TI  - Effects of Korean Red Ginseng (Panax ginseng), urushiol (Rhus vernicifera
      Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus
      acidophilus R0052) on the gut-liver axis of alcoholic liver disease.
AB  - BACKGROUND: Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely
      been established in the pathogenesis of alcoholic liver disease (ALD). METHODS:
      We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and
      probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in
      mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding
      groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol +
      urushiol, and alcohol + probiotics. Alcohol was administered via a Lieber-DeCarli
      liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines,
      and histology, as well as the results of liver function tests were evaluated and
      compared. RESULTS: No between-group differences were observed with regard to
      liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and
      probiotics groups than in the alcohol group (0.37 +/- 0.06 ng/mL, 0.39 +/- 0.12
      ng/mL, and 0.33 +/- 0.07 ng/mL, respectively, vs. 0.88 +/- 0.31 ng/mL; p < 0.05).
      Interleukin-1beta levels in liver tissues were decreased among the probiotics and
      KRG groups. The tumor necrosis factor-alpha level of liver tissue was decreased
      in the KRG group. CONCLUSION: The pathological findings showed that alcohol
      induced steatosis was significantly reduced by KRG and urushiol. As these agents
      improve immunologic capacity, they may be considered in potential anti-ALD
      treatments.

PMID- 25378991
TI  - Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and
      human rhinovirus 3.
AB  - BACKGROUND: Ginsenosides are the major components responsible for the biochemical
      and pharmacological actions of ginseng, and have been shown to have various
      biological activities. In this study, we investigated the antiviral activities of
      seven ginsenosides [protopanaxatriol (PT) type: Re, Rf, and Rg2; protopanaxadiol
      (PD) type: Rb1, Rb2, Rc, and Rd)] against coxsackievirus B3 (CVB3), enterovirus
      71 (EV71), and human rhinovirus 3 (HRV3). METHODS: Assays of antiviral activity
      and cytotoxicity were evaluated by the sulforhodamine B method using the
      cytopathic effect (CPE) reduction assay. RESULTS: The antiviral assays
      demonstrated that, of the seven ginsenosides, the PT-type ginsenosides (Re, Rf,
      and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a
      concentration of 100 MUg/mL. Among the PT-type ginsenosides, only ginsenoside Rg2
      showed significant anti-EV71 activity with no cytotoxicity to cells at 100
      MUg/mL. The PD-type ginsenosides (Rb1, Rb2, Rc, and Rd), by contrast, did not
      show any significant antiviral activity against CVB3, EV71, and HRV3, and
      exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral
      efficacies of PT-type ginsenosides were comparable to those of ribavirin, a
      commonly used antiviral drug. CONCLUSION: Collectively, our findings suggest that
      the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the
      treatment of CVB3, EV71, and HRV3 infection.

PMID- 25378992
TI  - Changes in ginsenoside compositions and antioxidant activities of hydroponic
      cultured ginseng roots and leaves with heating temperature.
AB  - BACKGROUND: This study evaluated changes in ginsenoside compositions and
      antioxidant activities in hydroponic-cultured ginseng roots (HGR) and leaves
      (HGL) with heating temperature. METHODS: Heat treatment was performed at
      temperatures of 90 degrees C, 110 degrees C, 130 degrees C, and 150 degrees C for
      2 hours. RESULTS: The ginsenoside content varied significantly with heating
      temperature. The levels of ginsenosides Rg1 and Re in HGR decreased with
      increasing heating temperature. Ginsenosides F2, F4, Rk3, Rh4, Rg3 (S form), Rg3
      (R form), Rk1, and Rg5, which were absent in the raw ginseng, were formed after
      heat treatment. The levels of ginsenosides Rg1, Re, Rf, and Rb1 in HGL decreased
      with increasing heating temperature. Conversely, ginsenosides Rk3, Rh4, Rg3 (R
      form), Rk1, and Rg5 increased with increasing heating temperature. In addition,
      ginsenoside contents of heated HGL were slightly higher than those of HGR. The
      highest extraction yield was 14.39% at 130 degrees C, whereas the lowest value
      was 10.30% at 150 degrees C. After heating, polyphenol contents of HGR and HGL
      increased from 0.43 mg gallic acid equivalent/g (mg GAE eq/g) and 0.74 mg GAE
      eq/g to 6.16 mg GAE eq/g and 2.86 mg GAE eq/g, respectively. CONCLUSION:
      Antioxidant activities of HGR and HGL, measured by 1,1-diphenyl-2-picrylhydrazyl
      and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging
      ability, increased with increasing heating temperature. These results may aid in
      improving the biological activity and quality of ginseng subjected to heat
      treatments.

PMID- 25378993
TI  - Discrimination of white ginseng origins using multivariate statistical analysis
      of data sets.
AB  - BACKGROUND: White ginseng (Panax ginseng Meyer) is commonly distributed as a
      health food in food markets. However, there is no practical method for
      distinguishing Korean white ginseng (KWG) from Chinese white ginseng (CWG),
      except for relying on the traceability system in the market. METHODS: Ultra
      performance liquid chromatography quadrupole time-of-flight mass spectrometry
      combined with orthogonal partial least squares discrimination analysis (OPLS-DA)
      was employed to discriminate between KWG and CWG. RESULTS: The origins of white
      ginsengs in two test sets (1.0 MUL and 0.2 MUL injections) could be successfully
      discriminated by the OPLS-DA analysis. From OPLS-DA S-plots, KWG exhibited
      tentative markers derived from ginsenoside Rf and notoginsenoside R3 isomer,
      whereas CWG exhibited tentative markers derived from ginsenoside Ro and
      chikusetsusaponin Iva. CONCLUSION: Results suggest that ultra-performance liquid
      chromatography quadrupole time-of-flight mass spectrometry coupled with OPLS-DA
      is an efficient tool for identifying the difference between the geographical
      origins of white ginsengs.

PMID- 25378994
TI  - Complete (1)H-NMR and (13)C-NMR spectral analysis of the pairs of 20(S) and 20(R)
      ginsenosides.
AB  - BACKGROUND: Ginsenosides, the major ingredients of Panax ginseng, have been
      studied for many decades in Asian countries as a result of their wide range of
      pharmacological properties. The less polar ginsenosides, with one or two sugar
      residues, are not present in nature and are produced during manufacturing
      processes by methods such as heating, steaming, acid hydrolysis, and enzyme
      reactions. (1)H-NMR and (13)C-NMR spectroscopic data for the identification of
      the less polar ginsenosides are often unavailable or incomplete. METHODS: We
      isolated 21 compounds, including 10 pairs of 20(S) and 20(R) less polar
      ginsenosides (1-20), and an oleanane-type triterpene (21) from a processed
      ginseng preparation and obtained complete (1)H-NMR and (13)C-NMR spectroscopic
      data for the following compounds, referred to as compounds 1-21 for rapid
      identification: 20(S)-ginsenosides Rh2 (1), 20(R)-Rh2 (2), 20(S)-Rg3 (3), 20(R)
      Rg3 (4), 6'-O-acetyl-20(S)-Rh2 [20(S)-AcetylRh2] (5), 20(R)-AcetylRh2 (6), 25
      hydroxy-20(S)-Rh2 (7), 25-hydroxy-20(S)-Rh2 (8), 20(S)-Rh1 (9), 20(R)-Rh1 (10),
      20(S)-Rg2 (11), 20(R)-Rg2 (12), 25-hydroxy-20(S)-Rh1 (13), 25-hydroxy-20(R)-Rh1
      (14), 20(S)-AcetylRg2 (15), 20(R)-AcetylRg2 (16), Rh4 (17), Rg5 (18), Rk1 (19),
      25-hydroxy-Rh4 (20), and oleanolic acid 28-O-beta-D-glucopyranoside (21).

PMID- 25378995
TI  - Effect of a soluble prebiotic fiber, NUTRIOSE, on the absorption of ginsenoside
      Rd in rats orally administered ginseng.
AB  - BACKGROUND: There is limited understanding of the effect of dietary components on
      the absorption of ginsenosides and their metabolites into the blood. METHODS:
      This study investigated the pharmacokinetics of the ginseng extract and its main
      constituent ginsenoside Rb1 in rats with or without pretreatment with a prebiotic
      fiber, NUTRIOSE, by liquid chromatography tandem mass spectrometry. When
      ginsenoside Rb1 was incubated with rat feces, its main metabolite was ginsenoside
      Rd. RESULTS: When the intestinal microbiota of rat feces were cultured in vitro,
      their ginsenoside Rd-forming activities were significantly induced by NUTRIOSE.
      When ginsenoside Rb1 was orally administered to rats, the maximum plasma
      concentration (Cmax) and area under the plasma drug concentration-time curve
      (AUC) for the main metabolite, ginsenoside Rd, were 72.4 +/- 31.6 ng/mL and 663.9
      +/- 285.3 MUg.h/mL, respectively. When the ginseng extract (2,000 mg/kg) was
      orally administered, Cmax and AUC for ginsenoside Rd were 906.5 +/- 330.2 ng/mL
      and 11,377.3 +/- 4,470.2 MUg.h/mL, respectively. When ginseng extract was orally
      administered to rats fed NUTRIOSE containing diets (2.5%, 5%, or 10%), Cmax and
      AUC were increased in the NUTRIOSE receiving groups in a dose-dependent manner.
      CONCLUSION: These findings reveal that intestinal microflora promote metabolic
      conversion of ginsenoside Rb1 and ginseng extract to ginsenoside Rd and promote
      its absorption into the blood in rats. Its conversion may be induced by prebiotic
      diets such as NUTRIOSE.

PMID- 25378996
TI  - Korean Red Ginseng saponin fraction modulates radiation effects on
      lipopolysaccharide-stimulated nitric oxide production in RAW264.7 macrophage
      cells.
AB  - BACKGROUND: In previous work, we reported that Korean Red Ginseng saponin
      fraction (RGSF) showed anti-inflammatory activities in vitro and in vivo.
      METHODS: The present study investigated the radioprotective properties of RGSF by
      examining its effects on ionizing radiation (IR)-enhanced and lipopolysaccharide
      (LPS)-mediated inflammatory responses in murine macrophage cells. RESULTS: RGSF
      induced strong downregulation of IR-enhanced and LPS-induced proinflammatory
      responses such as nitric oxide (NO) production (Inhibitory Concentration 50
      (IC50) = 5.1 +/- 0.8 MUM) and interleukin-1beta levels. RGSF was found to exert
      its radioprotective effects by inhibition of a signaling cascade that activated
      checkpoint kinase 2-nuclear factor-kappaB. In addition, RGSF strongly inhibited
      IR-enhanced LPS-induced expression of hemoxyganase-1, implying that the latter
      may be a potential target of RGSF. CONCLUSION: Taken together, our data suggest
      that RGSF can be considered and developed for use as an effective radioprotective
      agent with minimal adverse effects.

PMID- 25378997
TI  - Biological control of Colletotrichum panacicola on Panax ginseng by Bacillus
      subtilis HK-CSM-1.
AB  - BACKGROUND: Biological control of plant pathogens using benign or beneficial
      microorganisms as antagonistic agents is currently considered to be an important
      component of integrated pest management in agricultural crops. In this study, we
      evaluated the potential of Bacillus subtilis strain HK-CSM-1 as a biological
      control agent against Colletotrichum panacicola. METHODS: The potential of B.
      subtilis HK-CSM-1 as a biological control agent for ginseng anthracnose was
      assessed. C. panacicola was inoculated to ginseng plants and the incidence and
      severity of disease was assessed to examine the efficacy of the bacterium as a
      biological control against C. panacicola. RESULTS: Inoculation of Panax ginseng
      plants with B. subtilis significantly suppressed the number of disease lesions of
      C. panacicola and was as effective as the chemical fungicide iminoctadine
      tris(albesilate). The antifungal activity of B. subtilis against C. panacicola
      was observed on a co-culture medium. Interestingly, treatment with B. subtilis
      did not significantly affect the diameter of the lesions, suggesting that the
      mechanism of protection was through the reduction in the incidence of infection
      related to the initial events of the infection cycle, including penetration and
      infection via spore germination and appressorium formation rather than by the
      inhibition of invasive growth after infection. CONCLUSION: Our results suggest
      that B. subtilis HK-CSM-1 can be used as an effective and ecologically friendly
      biological control agent for anthracnose in P. ginseng.

PMID- 25378998
TI  - Plant regeneration of Korean wild ginseng (Panax ginseng Meyer) mutant lines
      induced by gamma-irradiation ((60)Co) of adventitious roots.
AB  - An efficient in vitro protocol has been established for somatic embryogenesis and
      plantlet conversion of Korean wild ginseng (Panax ginseng Meyer). Wild-type and
      mutant adventitious roots derived from the ginseng produced calluses on Murashige
      and Skoog (MS) medium supplemented with 0.5 mg/L 2,4-dichlorophenoxyacetic acid
      and 0.3 mg/L kinetin; 53.3% of the explants formed callus. Embryogenic callus
      proliferation and somatic embryo induction occurred on MS medium containing 0.5
      mg/L 2,4-dichlorophenoxyacetic acid. The induced somatic embryos further
      developed to maturity on MS medium with 5 mg/L gibberellic acid, and 85% of them
      germinated. The germinated embryos were developed to shoots and elongated on MS
      medium with 5 mg/L gibberellic acid. The shoots developed into plants with well
      developed taproots on one-third strength Schenk and Hildebrandt basal medium
      supplemented with 0.25 mg/L 1-naphthaleneacetic acid. When the plants were
      transferred to soil, about 30% of the regenerated plants developed into normal
      plants. 

PMID- 25378999
TI  - Red ginseng and H5N1 influenza infection.

PMID- 25379000
TI  - Research and implementation of good agricultural practice for traditional Chinese
      medicinal materials in Jilin Province, China.
AB  - Jilin Province is one of the principal production bases of traditional Chinese
      medicine (TCM) in China with its typical preponderance in TCM resources, research
      and development power, and industrialization capacity. The province has 2,790
      species of TCM materials in total. Over 20% of the TCM materials in common use
      are from Jilin Province. The province has established 36 good agricultural
      practice bases for 22 typical TCMs. The overall situation, in terms of
      collection, processing, and preparation, and the implementation of good
      agricultural practice of TCM materials in Jilin Province are summarized. 

PMID- 25379001
TI  - Ginseng total saponin modulates the changes of alpha-actinin-4 in podocytes
      induced by diabetic conditions.
AB  - BACKGROUND: The actin cytoskeleton in podocytes is essential for the maintenance
      of its normal structure and function. Its disruption is a feature of podocyte
      foot-process effacement and is associated with proteinuria. alpha-Actinin-4 in
      podocytes serves as a linker protein binding the actin filaments of the
      cytoskeleton. METHODS: To investigate the effect of ginseng total saponin (GTS)
      on the pathological changes of podocyte alpha-actinin-4 induced by diabetic
      conditions, we cultured mouse podocytes under normal glucose (5mM) or high
      glucose (HG, 30mM) conditions, with or without the addition of advanced
      glycosylation end products (AGE), and treated with GTS. RESULTS: In confocal
      imaging, alpha-actinin-4 colocalized with the ends of F-actin fibers in
      cytoplasm, but diabetic conditions disrupted F-actin fibers and concentrated
      alpha-actinin-4 molecules at the peripheral cytoplasm. GTS upregulated alpha
      actinin protein in a time- and dose-dependent manner, and suppressed the receptor
      for AGE levels in western blotting. Diabetic conditions, including HG, AGE, and
      both together, decreased cellular alpha-actinin-4 protein levels at 24 h and 48
      h. Such quantitative and qualitative changes of alpha-actinin-4 protein induced
      by diabetic conditions were mitigated by GTS. CONCLUSION: These findings imply
      that both HG and AGE have an influence on the distribution and amount of alpha
      actinin-4 in podocytes that can be recovered by GTS.

PMID- 25379002
TI  - An 8-wk, randomized, double-blind, placebo-controlled clinical trial for the
      antidiabetic effects of hydrolyzed ginseng extract.
AB  - BACKGROUND: To investigate the antidiabetic effects of hydrolyzed ginseng extract
      (HGE) for Korean participants in an 8-wk, randomized, double-blinded, placebo
      controlled clinical trial. METHODS: Impaired fasting glucose participants
      [fasting plasma glucose (FPG) >= 5.6mM or < 6.9mM] who had not been diagnosed
      with any disease and met the inclusion criteria were recruited for this study.
      The 23 participants were randomly divided into either the HGE (n = 12, 960 mg/d)
      or placebo (n = 11) group. Outcomes included measurements of efficacy (FPG,
      postprandial glucose, fasting plasma insulin, postprandial insulin, homeostatic
      model assessment-insulin resistance, and homeostatic model assessment-beta) and
      safety (adverse events, laboratory tests, electrocardiogram, and vital signs).
      RESULTS: After 8 wk of HGE supplementation, FPG and postprandial glucose were
      significantly decreased in the HGE group compared to the placebo group. No
      clinically significant changes in any safety parameter were observed. Our study
      revealed that HGE is a potent antidiabetic agent that does not produce noticeable
      adverse effects. CONCLUSION: HGE supplementation may be effective for treating
      impaired fasting glucose individuals.

PMID- 25379003
TI  - Rg3-enriched Korean Red Ginseng improves vascular function in spontaneously
      hypertensive rats.
AB  - BACKGROUND: Panax ginseng has distinct and impressive health benefits, such as
      improved blood pressure and immune system functioning. Rg3-enriched Korean Red
      Ginseng (REKRG) isolated from Korean Red Ginseng contains a high percentage of
      Rg3. METHODS: In this study, we examined the effects of REKRG on endothelial cell
      nitric oxide synthase (eNOS) activation and adhesion molecules in endothelial
      cells and vascular function in rats. RESULTS: REKRG dose-dependently increased
      eNOS phosphorylation and nitric oxide (NO) production in endothelial cells. In
      addition, REKRG markedly inhibited the tumor necrosis factor-alpha (TNF-alpha)
      mediated induction of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase
      (COX)-2 expressions in endothelial cells. REKRG improved endothelium-dependent
      vasorelaxation in the Wistar-Kyoto (WKY) rat and spontaneously hypertensive rats
      (SHRs) compared with controls. Furthermore, REKRG treatment for 6 weeks increased
      serum NO levels and reduced the mean aortic intima-media thickness compared with
      controls. CONCLUSION: Taken together, these results suggest that REKRG increased
      vascular function and improved immune system functioning. Therefore, REKRG is a
      very useful food for preventing or improving various cardiovascular diseases.

PMID- 25379004
TI  - Ginsenoside-Rp1-induced apolipoprotein A-1 expression in the LoVo human colon
      cancer cell line.
AB  - BACKGROUND: Ginsenoside Rp1 (G-Rp1) is a novel ginsenoside derived from
      ginsenoside Rk1. This compound was reported to have anticancer, anti-platelet,
      and anti-inflammatory activities. In this study, we examined the molecular target
      of the antiproliferative and proapoptotic activities of G-Rp1. METHODS: To
      examine the effects of G-Rp1, cell proliferation assays, propidium iodine
      staining, proteomic analysis by two-dimensional gel electrophoresis,
      immunoblotting analysis, and a knockdown strategy were used. RESULTS: G-Rp1 dose
      dependently suppressed the proliferation of colorectal cancer LoVo cells and
      increased their apoptosis. G-Rp1 markedly upregulated the protein level of
      apolipoprotein (Apo)-A1 in LoVo, SNU-407, DLD-1, SNU-638, AGS, KPL-4, and SK-BR-3
      cells. The knockdown of Apo-A1 by its small-interfering RNA increased the levels
      of cleaved poly(ADP-ribose) polymerase and p53 and diminished the proliferation
      of LoVo cells. CONCLUSION: These results suggest that G-Rp1 may act as an
      anticancer agent by strongly inhibiting cell proliferation and enhancing
      apoptosis through upregulation of Apo-A1.

PMID- 25379005
TI  - Korean Red Ginseng attenuates anxiety-like behavior during ethanol withdrawal in
      rats.
AB  - BACKGROUND: Korean Red Ginseng (KRG) is known to have antianxiety properties.
      This study was conducted to investigate the anxiolytic effects of KRG extract
      (KRGE) during ethanol withdrawal (EW) and the involvement of the mesoamygdaloid
      dopamine (DA) system in it. METHODS: Rats were treated with 3 g/kg/d of ethanol
      for 28 d, and subjected to 3 d of withdrawal. During EW, KRGE (20 mg/kg/d or 60
      mg/kg/d, p.o.) was given to rats once/d for 3 d. Thirty min after the final dose
      of KRGE, anxiety-like behavior was evaluated in an elevated plus maze (EPM), and
      plasma corticosterone (CORT) levels were determined by a radioimmunoassay (RIA).
      In addition, concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in
      the central nucleus of the amygdala (CeA) were also measured by high performance
      liquid chromatography (HPLC). RESULTS: The EPM test and RIA revealed KRGE
      inhibited anxiety-like behavior and the over secretion of plasma CORT during EW.
      Furthermore, the behavioral effect was blocked by a selective DA D2 receptor
      (D2R) antagonist (eticlopride) but not by a selective DA D1 receptor (D1R)
      antagonist (SCH23390). HPLC analyses showed KRGE reversed EW-induced decreases of
      DA and DOPAC in a dose-dependent way. Additionally, Western blotting and real
      time polymerase chain reaction (PCR) assays showed that KRGE prevented the EW
      induced reductions in tyrosine hydroxylase (TH) protein expression in the CeA and
      TH mRNA expression in the ventral tegmental area (VTA). CONCLUSION: These results
      suggest that KRGE has anxiolytic effects during EW by improving the
      mesoamygdaloid DA system.

PMID- 25379006
TI  - Enzymatic transformation of ginsenosides in Korean Red Ginseng (Panax ginseng
      Meyer) extract prepared by Spezyme and Optidex.
AB  - BACKGROUND: In this study, we examined the effects of various enzymes on chemical
      conversions of ginsenosides in ginseng extract prepared by amylases. METHODS:
      Rapidase, Econase CE, Viscozyme, Ultraflo L, and Cytolase PCL5 were used for
      secondary enzymatic hydrolysis after amylase treatment of ginseng extract, and
      ginsenoside contents, skin permeability, and chemical compositions including
      total sugar, acidic polysaccharide, and polyphenols were determined on the
      hydrolyzed ginseng extract. RESULTS: Rapidase treatment significantly elevated
      total ginsenoside contents compared with the control (p < 0.05). In particular,
      deglycosylated ginsenosides including Rg3, which are known as bioactive
      compounds, were significantly increased after Rapidase treatment (p < 0.05). The
      Rapidase-treated group also increased the skin permeability of polyphenols
      compared with the control, showing the highest level of total sugar content among
      the enzyme treatment groups. CONCLUSION: This result showed that Rapidase induced
      the conversion of ginsenoside glycosides to aglycones. Meanwhile, Cytolase PCL5
      and Econase treatments led to a significant increase of uronic acid (acidic
      polysaccharide) level. Taken together, our data showed that the treatments of
      enzymes including Rapidase are useful for the conversion and increase of
      ginsenosides in ginseng extracts or products.

PMID- 25379007
TI  - Investigation of ginsenosides in different tissues after elicitor treatment in
      Panax ginseng.
AB  - BACKGROUND: The effect of methyl jasmonate (MJ) on ginsenoside production in
      different organs of ginseng (Panax ginseng Meyer) was evaluated after the whole
      plant was dipped in an MJ-containing solution. MJ can induce the production of
      antioxidant defense genes and secondary metabolites in plants. In ginseng, MJ
      treatment in adventitious root resulted in the increase of dammarenediol synthase
      expression but a decrease of cycloartenol synthase expression, thereby enhancing
      ginsenoside biosynthesis. Although a previous study focused on the application of
      MJ to affect ginsenoside production in adventitious roots, we conducted our
      research on entire plants by evaluating the effect of exogenous MJ on ginsenoside
      production with the aim of obtaining new approaches to study ginsenoside
      biosynthesis response to MJ in vivo. METHODS: Different parts of MJ-treated
      ginseng plants were analyzed for ginsenoside contents (fine root, root body,
      epidermis, rhizome, stem, and leaf) by high-performance liquid chromatography.
      RESULTS: The total ginsenoside content of the ginseng root significantly
      increased after 2 d of MJ treatment compared with the control not subjected to
      MJ. Our results revealed that MJ treatment enhances ginsenoside production not in
      the epidermis but in the stele of the ginseng root, implying transportation of
      ginsenosides from the root vasculature to the epidermis. Application of MJ
      enhanced protopanaxadiol (PPD)-type ginsenosides, whereas chilling treatment
      induced protopanaxatriol (PPT)-type ginsenosides. CONCLUSION: These findings
      indicate that the production of PPD-type and PPT-type ginsenosides is differently
      affected by abiotic and biotic stresses in the ginseng plant, and they might play
      different defense mechanism roles.

PMID- 25379008
TI  - Transcriptome profiling and comparative analysis of Panax ginseng adventitious
      roots.
AB  - BACKGROUND: Panax ginseng Meyer is a traditional medicinal plant famous for its
      strong therapeutic effects and serves as an important herbal medicine. To
      understand and manipulate genes involved in secondary metabolic pathways
      including ginsenosides, transcriptome profiling of P. ginseng is essential.
      METHODS: RNA-seq analysis of adventitious roots of two P. ginseng cultivars,
      Chunpoong (CP) and Cheongsun (CS), was performed using the Illumina HiSeq
      platform. After transcripts were assembled, expression profiling was performed.
      RESULTS: Assemblies were generated from ~85 million and ~77 million high-quality
      reads from CP and CS cultivars, respectively. A total of 35,527 and 27,716
      transcripts were obtained from the CP and CS assemblies, respectively. Annotation
      of the transcriptomes showed that approximately 90% of the transcripts had
      significant matches in public databases. We identified several candidate genes
      involved in ginsenoside biosynthesis. In addition, a large number of transcripts
      (17%) with different gene ontology designations were uniquely detected in
      adventitious roots compared to normal ginseng roots. CONCLUSION: This study will
      provide a comprehensive insight into the transcriptome of ginseng adventitious
      roots, and a way for successful transcriptome analysis and profiling of resource
      plants with less genomic information. The transcriptome profiling data generated
      in this study are available in our newly created adventitious root transcriptome
      database (http://im-crop.snu.ac.kr/transdb/index.php) for public use.

PMID- 25379009
TI  - In vitro cytotoxic activity of ginseng leaf/stem extracts obtained by subcritical
      water extraction.
AB  - Ginseng leaf/stem extract produced by subcritical water extraction at high
      temperature (190 degrees C) possess higher cytotoxic activity against human
      cancer cell lines than ethanol extract. Subcritical water extraction can be a
      great candidate for extraction of functional substance from ginseng leaves/stems.

PMID- 25379010
TI  - A Wide Area of Air Pollutant Impact Downwind of a Freeway during Pre-Sunrise
      Hours.
AB  - We have observed a wide area of air pollutant impact downwind of a freeway during
      pre-sunrise hours in both winter and summer seasons. In contrast, previous
      studies have shown much sharper air pollutant gradients downwind of freeways,
      with levels above background concentrations extending only 300 m downwind of
      roadways during the day and up to 500 m at night. In this study, real-time air
      pollutant concentrations were measured along a 3 600 m transect normal to an
      elevated freeway 1-2 hours before sunrise using an electric vehicle mobile
      platform equipped with fast-response instruments. In winter pre-sunrise hours,
      the peak ultrafine particle (UFP) concentration (~95 000 cm-3) occurred
      immediately downwind of the freeway. However, downwind UFP concentrations as high
      as ~ 40 000 cm-3 extended at least 1 200 m from the freeway, and did not reach
      background levels (~15 000 cm-3) until a distance of about 2 600 m. UFP
      concentrations were also elevated over background levels up to 600 m upwind of
      the freeway. Other pollutants, such as NO and particle-bound polycyclic aromatic
      hydrocarbons, exhibited similar long-distance downwind concentration gradients.
      In contrast, air pollutant concentrations measured on the same route after
      sunrise, in the morning and afternoon, exhibited the typical daytime downwind
      decrease to background levels within ~300 m as found in earlier studies. Although
      pre-sunrise traffic volumes on the freeway were much lower than daytime
      congestion peaks, downwind UFP concentrations were significantly higher during
      pre-sunrise hours than during the daytime; UFP and NO concentrations were also
      strongly correlated with traffic counts on the freeway. We associate these
      elevated pre-sunrise concentrations over a wide area with a nocturnal surface
      temperature inversion, low wind speeds, and high relative humidity. Observation
      of a wide air pollutant impact area downwind of a major roadway prior to sunrise
      has important exposure assessment implications since it demonstrates extensive
      roadway impacts on residential areas during pre-sunrise hours, when most people
      are at home.

PMID- 25379011
TI  - Assessing language dominance in Mandarin-English bilinguals: Convergence and
      divergence between subjective and objective measures.
AB  - This study examines the convergence and divergence between subjective and
      objective measures of language proficiency for assessing language dominance in
      Mandarin-English bilinguals. Sixty-two young adults (Experiment 1) and 27
      children (Experiment 2) provided self-ratings of proficiency level (or were rated
      by their parents), were interviewed for spoken proficiency, and named pictures in
      the Multilingual Naming Test (MINT) and (in Experiment 1 only) the Boston Naming
      Test. In Experiment 1, the four measures converged in the number of people
      classified into different dominance groups but both naming tests indicated
      greater English dominance than self-report and interview measures. In Experiment
      2, parent report and interview measures converged in dominance classifications
      but the MINT indicated higher degrees of English dominance. To a large extent
      bilinguals were able to classify themselves (or their children) into dominance
      groups but some mismatches between measures in dominance classification were
      observed for all age and dominance groups. These results, together with previous
      findings with Spanish-English bilingual adults (Gollan et al., 2012), suggest
      that bilinguals may shift to English dominance in confrontation naming before
      they do so in conversational fluency, and that dominance shifts persist
      throughout the lifespan but may be relatively more pronounced in children. These
      findings caution against the use of self-reports as the sole means of classifying
      bilinguals into dominance groups and support a multi-measure approach including
      direct assessment of the relevant linguistic domain.

PMID- 25379013
TI  - Enhanced breast cancer therapy with nsPEFs and low concentrations of gemcitabine.
AB  - BACKGROUND: Chemotherapy either before or after surgery is a common breast cancer
      treatment. Long-term, high dose treatments with chemotherapeutic drugs often
      result in undesirable side effects, frequent recurrences and resistances to
      therapy. METHODS: The anti-cancer drug, gemcitabine (GEM) was used in combination
      with pulse power technology with nanosecond pulsed electric fields (nsPEFs) for
      treatment of human breast cancer cells in vitro. Two strategies include
      sensitizing mammary tumor cells with GEM before nsPEF treatment or sensitizing
      cells with nsPEFs before GEM treatment. Breast cancer cell lines MCF-7 and MDA-MB
      231 were treated with 250 65 ns-duration pulses and electric fields of 15, 20 or
      25 kV/cm before or after treatment with 0.38 MUM GEM. RESULTS: Both cell lines
      exhibited robust synergism for loss of cell viability 24 h and 48 h after
      treatment; treatment with GEM before nsPEFs was the preferred order. In
      clonogenic assays, only MDA-MB-231 cells showed synergism; again GEM before
      nsPEFs was the preferred order. In apoptosis/necrosis assays with Annexin-V
      FITC/propidium iodide 2 h after treatment, both cell lines exhibited apoptosis as
      a major cell death mechanism, but only MDA-MB-231 cells exhibited modest
      synergism. However, unlike viability assays, nsPEF treatment before GEM was
      preferred. MDA-MB-231 cells exhibited much greater levels of necrosis then in MCF
      7 cells, which were very low. Synergy was robust and greater when nsPEF treatment
      was before GEM. CONCLUSIONS: Combination treatments with low GEM concentrations
      and modest nsPEFs provide enhanced cytotoxicity in two breast cancer cell lines.
      The treatment order is flexible, although long-term survival and short-term cell
      death analyses indicated different treatment order preferences. Based on
      synergism, apoptosis mechanisms for both agents were more similar in MCF-7 than
      in MDA-MB-231 cells. In contrast, necrosis mechanisms for the two agents were
      distinctly different in MDA-MB-231, but too low to reliably evaluate in MCF-7
      cells. While disease mechanisms in the two cell lines are different based on the
      differential synergistic response to treatments, combination treatment with GEM
      and nsPEFs should provide an advantageous therapy for breast cancer ablation in
      vivo.

PMID- 25379014
TI  - Dynamic and influential interaction of cancer cells with normal epithelial cells
      in 3D culture.
AB  - BACKGROUND: The cancer microenvironment has a strong impact on the growth and
      dynamics of cancer cells. Conventional 2D culture systems, however, do not
      reflect in vivo conditions, impeding detailed studies of cancer cell dynamics.
      This work aims to establish a method to reveal the interaction of cancer and
      normal epithelial cells using 3D time-lapse. METHODS: GFP-labelled breast cancer
      cells, MDA-MB-231, were co-cultured with mCherry-labelled non-cancerous
      epithelial cells, MDCK, in a gel matrix. In the 3D culture, the epithelial cells
      establish a spherical morphology (epithelial sphere) thus providing cancer cells
      with accessibility to the basal surface of epithelia, similar to the in vivo
      condition. Cell movement was monitored using time-lapse analyses.
      Ultrastructural, immunocytochemical and protein expression analyses were also
      performed following the time-lapse study. RESULTS: In contrast to the 2D culture
      system, whereby most MDA-MB-231 cells exhibit spindle-shaped morphology as single
      cells, in the 3D culture the MDA-MB-231 cells were found to be single cells or
      else formed aggregates, both of which were motile. The single MDA-MB-231 cells
      exhibited both round and spindle shapes, with dynamic changes from one shape to
      the other, visible within a matter of hours. When co-cultured with epithelial
      cells, the MDA-MB-231 cells displayed a strong attraction to the epithelial
      spheres, and proceeded to surround and engulf the epithelial cell mass. The
      surrounded epithelial cells were eventually destroyed, becoming debris, and were
      taken into the MDA-MB-231 cells. However, when there was a relatively large
      population of normal epithelial cells, the MDA-MB-231 cells did not engulf the
      epithelial spheres effectively, despite repeated contacts. MDA-MB-231 cells co
      cultured with a large number of normal epithelial cells showed reduced expression
      of monocarboxylate transporter-1, suggesting a change in the cell metabolism. A
      decreased level of gelatin-digesting ability as well as reduced production of
      matrix metaroproteinase-2 was also observed. CONCLUSIONS: This culture method is
      a powerful technique to investigate cancer cell dynamics and cellular changes in
      response to the microenvironment. The method can be useful for various aspects
      such as; different combinations of cancer and non-cancer cell types, addressing
      the organ-specific affinity of cancer cells to host cells, and monitoring the
      cellular response to anti-cancer drugs.

PMID- 25379015
TI  - Tissue-infiltrating neutrophils constitute the major in vivo source of
      angiogenesis-inducing MMP-9 in the tumor microenvironment.
AB  - According to established notion, one of the major angiogenesis-inducing factors,
      pro-matrix metalloproteinase-9 (proMMP-9), is supplied to the tumor
      microenvironment by tumor-associated macrophages (TAMs). Accumulated evidence,
      however, indicates that tumor-associated neutrophils (TANs) are also critically
      important for proMMP-9 delivery, especially at early stages of tumor development.
      To clarify how much angiogenic proMMP-9 is actually contributed by TAMs and TANs,
      we quantitatively evaluated TAMs and TANs from different tumor types, including
      human xenografts and syngeneic murine tumors grown in wild-type and Mmp9-knockout
      mice. Whereas host MMP-9 competence was required for full angiogenic potential of
      both normal and tumor-associated leukocytes, direct comparisons of neutrophils
      versus macrophages and TANs versus TAMs demonstrated that macrophages and TAMs
      secrete 40- to 50-fold less proMMP-9 than the same numbers of neutrophils or
      TANs. Correspondingly, the levels of MMP-9-mediated in vivo angiogenesis induced
      by neutrophils and TANs substantially exceeded those induced by macrophages and
      TAMs. MMP-9-delivering TANs were also required for development of metastasis
      supporting intratumoral vasculature, characterized by >= 11-MUm size lumens and
      partial coverage with stabilizing pericytes. Importantly, MMP-9-producing TAMs
      exhibit M2-skewed phenotype but do not express tissue inhibitor of
      metalloproteinases-1 (TIMP-1), a novel characteristic allowing them to secrete
      TIMP-1-free, neutrophil-like MMP-9 zymogen unencumbered by its natural inhibitor.
      Together, our findings support the notion whereby TANs, capable of immediate
      release of their pre-stored cargo, are the major contributors of highly
      angiogenic MMP-9, whereas tumor-influxing precursors of macrophages require time
      to differentiate, polarize into M2-skewed TAMs, shut down their TIMP-1
      expression, and only then, initiate relatively low-level production of TIMP-free
      MMP-9 zymogen. 

PMID- 25379016
TI  - CK2 phosphorylates and inhibits TAp73 tumor suppressor function to promote
      expression of cancer stem cell genes and phenotype in head and neck cancer.
AB  - Cancer stem cells (CSC) and genes have been linked to cancer development and
      therapeutic resistance, but the signaling mechanisms regulating CSC genes and
      phenotype are incompletely understood. CK2 has emerged as a key signal
      serine/threonine kinase that modulates diverse signal cascades regulating cell
      fate and growth. We previously showed that CK2 is often aberrantly expressed and
      activated in head and neck squamous cell carcinomas (HNSCC), concomitantly with
      mutant (mt) tumor suppressor TP53, and inactivation of its family member, TAp73.
      Unexpectedly, we observed that classical stem cell genes Nanog, Sox2, and Oct4,
      are overexpressed in HNSCC with inactivated TAp73 and mtTP53. However, the
      potential relationship between CK2, TAp73 inactivation, and CSC phenotype is
      unknown. We reveal that inhibition of CK2 by pharmacologic inhibitors or siRNA
      inhibits the expression of CSC genes and side population (SP), while enhancing
      TAp73 mRNA and protein expression. Conversely, CK2 inhibitor attenuation of CSC
      protein expression and the SP by was abrogated by TAp73 siRNA. Bioinformatic
      analysis uncovered a single predicted CK2 threonine phosphorylation site (T27)
      within the N-terminal transactivation domain of TAp73. Nuclear CK2 and TAp73
      interaction, confirmed by co-immunoprecipitation, was attenuated by CK2
      inhibitor, or a T27A point-mutation of this predicted CK2 threonine phospho
      acceptor site of TAp73. Further, T27A mutation attenuated phosphorylation, while
      enhancing TAp73 function in repressing CSC gene expression and SP cells. A new
      CK2 inhibitor, CX-4945, inhibited CSC related SP cells, clonogenic survival, and
      spheroid formation. Our study unveils a novel regulatory mechanism whereby
      aberrant CK2 signaling inhibits TAp73 to promote the expression of CSC genes and
      phenotype. 

PMID- 25379017
TI  - FLI1 expression is correlated with breast cancer cellular growth, migration, and
      invasion and altered gene expression.
AB  - ETS factors have been shown to be dysregulated in breast cancer. ETS factors
      control the expression of genes involved in many biological processes, such as
      cellular proliferation, differentiation, and apoptosis. FLI1 is an ETS protein
      aberrantly expressed in retrovirus-induced hematological tumors, but limited
      attention has been directed towards elucidating the role of FLI1 in epithelial
      derived cancers. Using data mining, we show that loss of FLI1 expression is
      associated with shorter survival and more aggressive phenotypes of breast cancer.
      Gain and loss of function cellular studies indicate the inhibitory effect of FLI1
      expression on cellular growth, migration, and invasion. Using Fli1 mutant mice
      and both a transgenic murine breast cancer model and an orthotopic injection of
      syngeneic tumor cells indicates that reduced Fli1 contributes to accelerated
      tumor growth. Global expression analysis and RNA-Seq data from an invasive human
      breast cancer cell line with over expression of either FLI1 and another ETS gene,
      PDEF, shows changes in several cellular pathways associated with cancer, such as
      the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways. This
      study demonstrates a novel role for FLI1 in epithelial cells. In addition, these
      results reveal that FLI1 down-regulation in breast cancer may promote tumor
      progression. 

PMID- 25379018
TI  - The presence of telomere fusion in sporadic colon cancer independently of disease
      stage, TP53/KRAS mutation status, mean telomere length, and telomerase activity.
AB  - Defects in telomere maintenance can result in telomere fusions that likely play a
      causative role in carcinogenesis by promoting genomic instability. However, this
      proposition remains to be fully understood in human colon carcinogenesis. In the
      present study, the temporal sequence of telomere dysfunction dynamics was
      delineated by analyzing telomere fusion, telomere length, telomerase activity,
      hotspot mutations in KRAS or BRAF, and TP53 of tissue samples obtained from 18
      colon cancer patients. Our results revealed that both the deficiency of p53 and
      the shortening of mean telomere length were not necessary for producing telomere
      fusions in colon tissue. In five cases, telomere fusion was observed even in
      tissue adjacent to cancerous lesions, suggesting that genomic instability is
      initiated in pathologically non-cancerous lesions. The extent of mean telomere
      attrition increased with lymph node invasiveness of tumors, implying that mean
      telomere shortening correlates with colon cancer progression. Telomerase activity
      was relatively higher in most cancer tissues containing mutation(s) in KRAS or
      BRAF and/or TP53 compared to those without these hotspot mutations, suggesting
      that telomerase could become fully active at the late stage of colon cancer
      development. Interestingly, the majority of telomere fusion junctions in colon
      cancer appeared to be a chromatid-type containing chromosome 7q or 12q. In sum,
      this meticulous correlative study not only highlights the concept that telomere
      fusion is present in the early stages of cancer regardless of TP53/KRAS mutation
      status, mean telomere length, and telomerase activity, but also provides
      additional insights targeting key telomere fusion junctions which may have
      significant implications for colon cancer diagnoses. 

PMID- 25379020
TI  - A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy
      for the treatment of melanoma.
AB  - Melanomas are highly radioresistant tumors, mainly due to efficient DNA double
      strand break (DSB) repair. Dbait (which stands for DNA strand break bait)
      molecules mimic DSBs and trap DNA repair proteins, thereby inhibiting repair of
      DNA damage induced by radiation therapy (RT). First, the cytotoxic efficacy of
      Dbait in combination with RT was evaluated in vitro in SK28 and 501mel human
      melanoma cell lines. Though the extent of RT-induced damage was not increased by
      Dbait, it persisted for longer revealing a repair defect. Dbait enhanced RT
      efficacy independently of RT doses. We further assayed the capacity of DT01
      (clinical form of Dbait) to enhance efficacy of "palliative" RT (10 * 3 Gy) or
      "radical" RT (20 * 3 Gy), in an SK28 xenografted model. Inhibition of repair of
      RT-induced DSB by DT01 was revealed by the significant increase of micronuclei in
      tumors treated with combined treatment. Mice treated with DT01 and RT combination
      had significantly better tumor growth control and longer survival compared to RT
      alone with the "palliative" protocol [tumor growth delay (TGD) by 5.7-fold;
      median survival: 119 vs 67 days] or the "radical" protocol (TGD by 3.2-fold;
      median survival: 221 vs 109 days). Only animals that received the combined
      treatment showed complete responses. No additional toxicity was observed in any
      DT01-treated groups. This preclinical study provides encouraging results for a
      combination of a new DNA repair inhibitor, DT01, with RT, in the absence of
      toxicity. A first-in-human phase I study is currently under way in the palliative
      management of melanoma in-transit metastases (DRIIM trial).

PMID- 25379019
TI  - Inhibition of p70 S6 kinase (S6K1) activity by A77 1726 and its effect on cell
      proliferation and cell cycle progress.
AB  - Leflunomide is a novel immunomodulatory drug prescribed for treating rheumatoid
      arthritis. It inhibits the activity of protein tyrosine kinases and
      dihydroorotate dehydrogenase, a rate-limiting enzyme in the pyrimidine nucleotide
      synthesis pathway. Here, we report that A77 1726, the active metabolite of
      leflunomide, inhibited the phosphorylation of ribosomal protein S6 and two other
      substrates of S6K1, insulin receptor substrate-1 and carbamoyl phosphate
      synthetase 2, in an A375 melanoma cell line. A77 1726 increased the
      phosphorylation of AKT, p70 S6 (S6K1), ERK1/2, and MEK through the feedback
      activation of the IGF-1 receptor-mediated signaling pathway. In vitro kinase
      assay revealed that leflunomide and A77 1726 inhibited S6K1 activity with IC50
      values of approximately 55 and 80 MUM, respectively. Exogenous uridine partially
      blocked A77 1726-induced inhibition of A375 cell proliferation. S6K1 knockdown
      led to the inhibition of A375 cell proliferation but did not potentiate the
      antiproliferative effect of A77 1726. A77 1726 stimulated bromodeoxyuridine
      incorporation in A375 cells but arrested the cell cycle in the S phase, which was
      reversed by addition of exogenous uridine or by MAP kinase pathway inhibitors but
      not by rapamycin and LY294002 (a phosphoinositide 3-kinase inhibitor). These
      observations suggest that A77 1726 accelerates cell cycle entry into the S phase
      through MAP kinase activation and that pyrimidine nucleotide depletion halts the
      completion of the cell cycle. Our study identified a novel molecular target of
      A77 1726 and showed that the inhibition of S6K1 activity was in part responsible
      for its antiproliferative activity. Our study also provides a novel mechanistic
      insight into A77 1726-induced cell cycle arrest in the S phase. 

PMID- 25379021
TI  - Resistance to Selumetinib (AZD6244) in colorectal cancer cell lines is mediated
      by p70S6K and RPS6 activation.
AB  - Selumetinib (AZD6244, ARRY-142886) is a MEK1/2 inhibitor that has gained interest
      as an anti-tumour agent. We have determined the degree of sensitivity/resistance
      to Selumetinib in a panel of colorectal cancer cell lines using cell
      proliferation and soft agar assays. Sensitive cell lines underwent G1 arrest,
      whereas Selumetinib had no effect on the cell cycle of resistant cells. Some of
      the resistant cell lines showed high levels of ERK1/2 phosphorylation in the
      absence of serum. Selumetinib inhibited phosphorylation of ERK1/2 and RSK and had
      no effect on AKT phosphorylation in both sensitive and resistant cells.
      Furthermore, mutations in KRAS, BRAF, or PIK3CA were not clearly associated with
      Selumetinib resistance. Surprisingly, Selumetinib was able to inhibit
      phosphorylation of p70 S6 kinase (p70S6K) and its downstream target ribosomal
      protein S6 (RPS6) in sensitive cell lines. However, p70S6K and RPS6
      phosphorylation remained unaffected or even increased in resistant cells.
      Moreover, in some of the resistant cell lines p70S6K and RPS6 were phosphorylated
      in the absence of serum. Interestingly, colorectal primary cultures derived from
      tumours excised to patients exhibited the same behaviour than established cell
      lines. Pharmacological inhibition of p70S6K using the PI3K/mTOR inhibitor NVP
      BEZ235, the specific mTOR inhibitor Rapamycin and the specific p70S6K inhibitor
      PF-4708671 potentiated Selumetinib effects in resistant cells. In addition,
      biological inhibition of p70S6K using siRNA rendered responsiveness to
      Selumetinib in resistant cell lines. Furthermore, combination of p70S6K silencing
      and PF-47086714 was even more effective. We can conclude that p70S6K and its
      downstream target RPS6 are potential biomarkers of resistance to Selumetinib in
      colorectal cancer. 

PMID- 25379022
TI  - Chromosome 17 centromere duplication and responsiveness to anthracycline-based
      neoadjuvant chemotherapy in breast cancer.
AB  - Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha
      (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to
      anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe
      (CEP17) duplication has also been associated with increased responsiveness to
      anthracyclines. However, reports are conflicting and none of these tumor markers
      can yet be considered a clinically reliable predictor of response to
      anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene
      amplification, and CEP17 duplication with response to anthracycline-based
      neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast
      cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17
      by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved
      pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%)
      of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17
      duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with
      a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25
      34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on
      statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A
      amplification and CEP17 duplication combined were strongly associated with pCR
      (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with
      pCR. Our results suggest that CEP17 duplication predicts pCR to primary
      anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and
      HER2 amplifications were not associated with prognosis. 

PMID- 25379023
TI  - Adrenal medullary hyperplasia is a precursor lesion for pheochromocytoma in MEN2
      syndrome.
AB  - Adrenal medullary hyperplasias (AMHs) are adrenal medullary proliferations with a
      size < 1 cm, while larger lesions are considered as pheochromocytoma (PCC). This
      arbitrary distinction has been proposed decades ago, although the biological
      relationship between AMH and PCC has never been investigated. Both lesions are
      frequently diagnosed in multiple endocrine neoplasia type 2 (MEN2) patients in
      whom they are considered as two unrelated clinical entities. In this study, we
      investigated the molecular relationship between AMH and PCC in MEN2 patients.
      Molecular aberrations of 19 AMHs and 13 PCCs from 18 MEN2 patients were
      determined by rearranged during transfection (RET) proto-oncogene mutation
      analysis and loss of heterozygosity (LOH) analysis for chromosomal regions 1p13,
      1p36, 3p, and 3q, genomic areas covering commonly altered regions in RET-related
      PCC. Identical molecular aberrations were found in all AMHs and PCCs, at similar
      frequencies. LOH was seen for chromosomes 1p13 in 8 of 18 (44%), 1p36 in 9 of 15
      (60%), 3p12-13 in 12 of 18 (67%), and 3q23-24 in 10 of 16 (63%) of AMHs, and for
      chromosome 1p13 in 13 of 13 (100%), 1p36 in 7 of 11 (64%), 3p12-13 in 4 of 11
      (36%), and 3q23-24 in 11 of 12 (92%) of PCCs. Our results indicate that AMHs are
      not hyperplasias and, in clinical practice, should be regarded as PCCs, which has
      an impact on diagnosis and treatment of MEN2 patients. We therefore propose to
      replace the term AMH by micro-PCC to indicate adrenal medullary proliferations of
      less than 1 cm.

PMID- 25379025
TI  - (Self-)Surveillance, Anti-Doping, and Health in Non-Elite Road Running.

PMID- 25379024
TI  - Therapeutic efficacy of aldoxorubicin in an intracranial xenograft mouse model of
      human glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a
      median survival of 12 to 15 months after diagnosis. Acquired chemoresistance,
      high systemic toxicity, and low penetration of the blood brain barrier by many
      anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent
      some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM
      efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin
      (Aldoxo), which is less toxic, is released from albumin in an acidic environment
      and accumulates in tumor tissues. A human GBM cell line that expresses a
      luciferase reporter (U87-luc) was stereotactically injected into the left
      striatum of the brain of immunodeficient mice. Following initial tumor growth for
      12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or
      18 mg/kg of doxorubicin equivalents-3/4 maximum tolerated dose (MTD)], Doxo [6
      mg/kg (3/4 MTD)], or vehicle. Aldoxo-treated mice demonstrated significantly
      slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice.
      Five out of eight Aldoxo-treated mice remained alive more than 60 days with a
      median survival of 62 days, while the median survival of vehicle- and Doxo
      treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high
      levels of Doxo within the tumor tissue, accompanied by low tumor cell
      proliferation (Ki67) and abundant intratumoral programmed cell death (cleaved
      caspase-3). Effective accumulation of Aldoxo in brain tumor tissues but not
      normal brain, its anti-tumor efficacy, and low toxicity, provide a strong
      rationale for evaluating this novel drug conjugate as a treatment for patients
      afflicted with GBM. 

PMID- 25379026
TI  - Ten-year trends in major lifestyle risk factors using an ongoing population
      surveillance system in Australia.
AB  - BACKGROUND: Understanding how risk factors (tobacco, alcohol, physical
      inactivity, unhealthy diet, high blood pressure, and high cholesterol) change
      over time is a critical aim of public health. The associations across the social
      gradient over time are important considerations. Risk factor surveillance systems
      have a part to play in understanding the epidemiological distribution of the risk
      factors so as to improve preventive measures and design public health
      interventions for reducing the burden of disease. METHODS: Representative, cross
      sectional data were collected in South Australia using telephone interviews,
      conducted on a minimum of 600 randomly selected people (of all ages) each month.
      Data were collected from January 2004 to December 2013. Unadjusted prevalence
      over time, the relative percentage change over the 10 years, and the absolute
      change of the risk factors with sex, age group, and socio-economic status (SES)
      estimates are presented. RESULTS: In total 55,548 adults (>=18 years) were
      interviewed (mean age = 47.8 years, 48.8% male). Decreases were apparent for
      insufficient physical activity, inadequate fruit and vegetables, smoking, and
      soft drink consumption of >=500 ml/day. Increases were found over the 10 years
      for obesity, high cholesterol, diabetes, and for those with no risk factors.
      Apparent differences were noticeable by different sex, age, and SES categories.
      While increases in physical activity and fruit and vegetable consumption and
      decreases in smoking prevalence and multiple risk factors are to be expected in
      2020-2021, the prevalence of obesity, high blood pressure, high cholesterol, and
      diabetes are expected to increase. CONCLUSIONS: Public health efforts in
      increasing the proportion of the population undertaking appropriate risk factor
      behavior are showing signs of success, with data from 2004 to 2013 showing
      encouraging trends. Deriving comparable trends over time by key demographics and
      SES variables provides evidence for policymakers and health planners to encourage
      interventions aimed at preventing chronic disease.

PMID- 25379027
TI  - In vivo characterization of brain iron with magnetic field correlation imaging.

PMID- 25379028
TI  - Assessing TLI as a Predictor of Treatment Seeking for SUD among Youth
      Transitioning to Young Adulthood.
AB  - BACKGROUND: To date, few studies have been conducted evaluating predictors of
      treatment seeking for substance use disorders as persons make the transition from
      preadolescence (a period of very low substance use) to young adulthood (a period
      of peak substance use). The few studies of this area which have been conducted to
      date have generally been limited by their use of a cross-sectional rather than a
      longitudinal study design. We have conducted a longitudinal etiology study
      (CEDAR) to assess whether an index of behavioral undercontrol called the
      Transmissible Liability Index (TLI) measured during preadolescence serves as a
      predictor of the development of substance use disorders (SUD) and of treatment
      utilization during young adulthood. Our recent work has focuses on subjects with
      cannabis use disorders (CUD), since CUD are the most common SUD. In recent
      analyses, we found that TLI serves as a predictor of the development of cannabis
      use disorder (CUD) among young adults (Kirisci et al., 2009). OBJECTIVE: In the
      current study, we hypothesized that TLI as assessed during preadolescence would
      predict treatment seeking a decade later when the subjects were young adults.
      METHOD: The 375 participants in this study were initially recruited when they
      were 10-12 years of age. TLI status was determined at baseline, and subsequent
      assessments were conducted at 12-14, 16, 19, and 22 years of age. Variables
      examined included TLI as well as demographic variables. Path analyses were
      conducted. RESULTS: Of the 375 subjects recruited at age 10-12, 92 subjects
      (24.5%) were diagnosed with a CUD by the age of 22. TLI as assessed during pre
      adolescence (at age 10 to 12) was found to be associated with substance-related
      treatment during young adulthood (age 19 and at age 22). CONCLUSIONS: These
      findings confirmed our hypothesis that TLI assessed during preadolescent years
      serves as a predictor of treatment at age 19 and at age 22.

PMID- 25379029
TI  - Correlates of Posttraumatic Growth in Adult Sexual Assault Victims.
AB  - This exploratory study examined how demographics, child sexual abuse (CSA),
      assault-related factors, and post-assault responses predict posttraumatic growth
      in a diverse sample (N = 1863) of female adult sexual assault victims. Multiple
      regression analysis showed that demographics (older age, ethnic minority race,
      less education) were all significantly related to greater posttraumatic growth,
      while CSA was unrelated to posttraumatic growth. Assault characteristics were
      weaker predictors of posttraumatic growth; whereas women's perception of life
      threat during the assault was related to greater posttraumatic growth. Post
      assault factors including: greater levels of maladaptive coping,
      characterological self-blame, negative social reactions from others, and
      posttraumatic stress disorder (PTSD) symptoms were all related to less
      posttraumatic growth. Conversely, positive social reactions from others,
      perceived control over recovery, adaptive individual coping, and disrupted core
      beliefs were all related to greater posttraumatic growth. Clinicians should
      facilitate these modifiable social psychological factors when treating survivors.

PMID- 25379030
TI  - Securing Information Technology in Healthcare.
AB  - Dartmouth College's Institute for Security, Technology, and Society conducted
      three workshops on securing information technology in healthcare, attended by a
      diverse range of experts in the field. This article summarizes the three
      workshops.

PMID- 25379031
TI  - Effects of a carbohydrate-electrolyte solution on cognitive performance following
      exercise-induced hyperthermia in humans.
AB  - BACKGROUND: There is limited information on the effects of sports drinks on
      cognitive function after exercise in the heat. We aimed to investigate the
      effects of ingesting a commercially available carbohydrate-electrolyte (CHO)
      solution on cognitive performance following exercise-induced hyperthermia.
      METHODS: Twelve participants completed three practices of cognitive tests, one
      full familiarisation and two experimental trials in an environmental chamber (dry
      bulb temperature: 30.2 +/- 0.3 degrees C, relative humidity: 70 +/- 3%). The
      experimental trials consisted of five cognitive tests (symbol digit matching,
      search and memory, digit span, choice reaction time and psychomotor vigilance
      test) performed before and after a 75-min run on a treadmill at 70% VO2 max. One
      ml/kg body mass of a 6.8% CHO solution or placebo was consumed at the start,
      every 15 min during exercise and between cognitive tests after exercise. Core
      temperature, heart rate, blood glucose concentrations, subjective ratings and
      cognitive performance were assessed (symbol digit matching, search and memory,
      digit span, choice reaction time and psychomotor vigilance). RESULTS:
      Participants were hyperthermic at the end of the run (placebo: 39.5 +/- 0.4
      degrees C, CHO: 39.6 +/- 0.5 degrees C; Mean +/- SD; p = 0.37). The change in
      blood glucose was higher with CHO ingestion (1.6, 0.7 to 4.5 mmol/L) (median,
      range) than with placebo ingestion (0.9, -0.1 to 4.7 mmol/L; p < 0.05). CHO
      ingestion reduced the maximum span of digits memorized, in contrast to an
      increase in maximum span with placebo ingestion (p < 0.05). CHO solution had no
      effect on other cognitive tests (p > 0.05). CONCLUSIONS: These results suggest
      that CHO solution ingestion may impair short-term memory following exertional
      heat stress.

PMID- 25379032
TI  - BINGE DRINKING, SMOKING AND MARIJUANA USE: THE ROLE OF WOMEN's LABOR FORCE
      PARTICIPATION.
AB  - This study analyzed the role of women's labor force participation in relation to
      binge drinking, smoking and marijuana use among employment age married/cohabiting
      women. The sample consisted of 956 women who were employed as construction
      workers (n=104), or were unemployed (n=101), homemakers (n=227) or employed in
      non-physically demanding occupations (n=524). Results of multivariate logistic
      regression analyses showed that women construction workers were at elevated risk
      for smoking and monthly binge drinking; unemployed women were more likely to use
      marijuana. Women in both categories were at risk for polysubstance use.
      Additional research is needed to explicate how labor force participation
      influences women's substance use.

PMID- 25379033
TI  - Proteomic analysis of human plasma in chronic rheumatic mitral stenosis reveals
      proteins involved in the complement and coagulation cascade.
AB  - BACKGROUND: Rheumatic fever in childhood is the most common cause of Mitral
      Stenosis in developing countries. The disease is characterized by damaged and
      deformed mitral valves predisposing them to scarring and narrowing (stenosis)
      that results in left atrial hypertrophy followed by heart failure. Presently,
      echocardiography is the main imaging technique used to diagnose Mitral Stenosis.
      Despite the high prevalence and increased morbidity, no biochemical indicators
      are available for prediction, diagnosis and management of the disease. Adopting a
      proteomic approach to study Rheumatic Mitral Stenosis may therefore throw some
      light in this direction. In our study, we undertook plasma proteomics of human
      subjects suffering from Rheumatic Mitral Stenosis (n = 6) and Control subjects (n
      = 6). Six plasma samples, three each from the control and patient groups were
      pooled and subjected to low abundance protein enrichment. Pooled plasma samples
      (crude and equalized) were then subjected to in-solution trypsin digestion
      separately. Digests were analyzed using nano LC-MS(E). Data was acquired with the
      Protein Lynx Global Server v2.5.2 software and searches made against reviewed
      Homo sapiens database (UniProtKB) for protein identification. Label-free protein
      quantification was performed in crude plasma only. RESULTS: A total of 130
      proteins spanning 9-192 kDa were identified. Of these 83 proteins were common to
      both groups and 34 were differentially regulated. Functional annotation of
      overlapping and differential proteins revealed that more than 50% proteins are
      involved in inflammation and immune response. This was corroborated by findings
      from pathway analysis and histopathological studies on excised tissue sections of
      stenotic mitral valves. Verification of selected protein candidates by
      immunotechniques in crude plasma corroborated our findings from label-free
      protein quantification. CONCLUSIONS: We propose that this protein profile of
      blood plasma, or any of the individual proteins, could serve as a focal point for
      future mechanistic studies on Mitral Stenosis. In addition, some of the proteins
      associated with this disorder may be candidate biomarkers for disease diagnosis
      and prognosis. Our findings might help to enrich existing knowledge on the
      molecular mechanisms involved in Mitral Stenosis and improve the current
      diagnostic tools in the long run.

PMID- 25379035
TI  - A Novel Human Radixin Peptide Inhibits Hepatitis C Virus Infection at the Level
      of Cell Entry.
AB  - Hepatitis C virus infection of hepatocytes is a multistep process involving the
      interaction between viral and host cell molecules. Recently, we identified ezrin
      moesin-radixin proteins and spleen tyrosine kinase (SYK) as important host
      therapeutic targets for HCV treatment development. Previously, an ezrin hinge
      region peptide (Hep1) has been shown to exert anti-HCV properties in vivo, though
      its mechanism of action remains limited. In search of potential novel inhibitors
      of HCV infection and their functional mechanism we analyzed the anti-HCV
      properties of different human derived radixin peptides. Sixteen different radixin
      peptides were derived, synthesized and tested. Real-time quantitative PCR, cell
      toxicity assay, immuno-precipitation/western blot analysis and computational
      resource for drug discovery software were used for experimental analysis. We
      found that a human radixin hinge region peptide (Peptide1) can specifically block
      HCV J6/JFH-1 infection of Huh7.5 cells. Peptide 1 had no cell toxicity or
      intracellular uptake into Huh7.5 cells. Mechanistically, the anti-HCV activity of
      Peptide 1 extended to disruption of HCV engagement of CD81 thereby blocking
      downstream SYK activation, which we have recently demonstrated to be important
      for effective HCV infection of target hepatocytes. Our findings highlight a novel
      functional class of anti-HCV agents that can inhibit HCV infection, most likely
      by disrupting vital viral-host signaling interactions at the level of virus
      entry.

PMID- 25379034
TI  - Medicinal history of North American Veratrum.
AB  - Plants belonging to the genus Veratrum have been used throughout history for
      their medicinal properties. During the nineteenth and twentieth centuries,
      phytochemical investigations revealed a host of steroidal alkaloids in Veratrum
      species, some of which are potent bioactives. This review discusses Veratrum
      species that grow in North America with a focus on the medicinal history of these
      plants and the steroidal alkaloids they contain. While significant reviews have
      been devoted to singularly describing the plant species within the genus Veratrum
      (botany), the staggering breadth of alkaloids isolated from these and related
      plants (phytochemistry), and the intricacies of how the various alkaloids act on
      their biological targets (physiology and biochemistry), this review will straddle
      the margins of the aforementioned disciplines in an attempt to provide a unified,
      coherent picture of the Veratrum plants of North America and the medicinal uses
      of their bioactive steroidal alkaloids.

PMID- 25379036
TI  - Research staff training in a multisite randomized clinical trial: Methods and
      recommendations from the Stimulant Reduction Intervention using Dosed Exercise
      (STRIDE) trial.
AB  - BACKGROUND: Descriptions of and recommendations for meeting the challenges of
      training research staff for multisite studies are limited despite the recognized
      importance of training on trial outcomes. The STRIDE (STimulant Reduction
      Intervention using Dosed Exercise) study is a multisite randomized clinical trial
      that was conducted at nine addiction treatment programs across the United States
      within the National Drug Abuse Treatment Clinical Trials Network (CTN) and
      evaluated the addition of exercise to addiction treatment as usual (TAU),
      compared to health education added to TAU, for individuals with stimulant abuse
      or dependence. Research staff administered a variety of measures that required a
      range of interviewing, technical, and clinical skills. PURPOSE: In order to
      address the absence of information on how research staff are trained for
      multisite clinical studies, the current manuscript describes the conceptual
      process of training and certifying research assistants for STRIDE. METHODS:
      Training was conducted using a three-stage process to allow staff sufficient time
      for distributive learning, practice, and calibration leading up to implementation
      of this complex study. RESULTS: Training was successfully implemented with staff
      across nine sites. Staff demonstrated evidence of study and procedural knowledge
      via quizzes and skill demonstration on six measures requiring certification.
      Overall, while the majority of staff had little to no experience in the six
      measures, all research assistants demonstrated ability to correctly and reliably
      administer the measures throughout the study. CONCLUSIONS: Practical
      recommendations are provided for training research staff and are particularly
      applicable to the challenges encountered with large, multisite trials.

PMID- 25379038
TI  - Significance of antigen and epitope specificity in tuberculosis.

PMID- 25379037
TI  - A novel model for development, organization, and function of gonadotropes in fish
      pituitary.
AB  - The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
      are key regulators of the reproductive axis in vertebrates. Despite the high
      popularity of zebrafish as a model organism for studying reproductive functions,
      to date no transgenic zebrafish with labeled gonadotropes have been introduced.
      Using gonadotropin regulatory elements from tilapia, we generated two transgenic
      zebrafish lines with labeled gonadotropes. The tilapia and zebrafish regulatory
      sequences were highly divergent but several conserved elements allowed the
      tilapia promoters to correctly drive the transgenes in zebrafish pituitaries. FSH
      cells reacted to stimulation with gonadotropin releasing hormone by proliferating
      and showing increased transgene fluorescence, whereas estrogen exposure caused a
      decrease in cell number and transgene fluorescence. Transgene fluorescence
      reflected the expression pattern of the endogenous fshb gene. Ontogenetic
      expression of the transgenes followed typical patterns, with FSH cells appearing
      early in development, and LH cells appearing later and increasing dramatically in
      number with the onset of puberty. Our transgenic lines provide a powerful tool
      for investigating the development, anatomy, and function of the reproductive axis
      in lower vertebrates. 

PMID- 25379039
TI  - Impairment of hepatic and renal functions by 2,5-hexanedione is accompanied by
      oxidative stress in rats.
AB  - 2,5-Hexanedione (2,5-HD) is the toxic metabolite of n-hexane which is widely used
      as solvent in numerous industries. The present study elucidated the precise
      mechanism of 2,5-HD in hepatorenal toxicity by determining the involvement of
      oxidative stress in rats. Adult male Wistar rats were exposed to 0, 0.25, 0.5,
      and 1% 2,5-HD in drinking water for 21 days. Exposure to 2,5-HD caused liver and
      kidney atrophy evidenced by significant elevation in serum aminotransferases,
      alkaline phosphatase, albumin, bilirubin, urea, creatinine, and electrolytes
      levels compared with control. The marked dose-dependent increase in total
      cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) was
      accompanied with significant decrease in high-density lipoprotein (HDL) levels in
      2,5-HD-exposed animals when compared with the control. Administration of 2,5-HD
      significantly diminished glutathione (GSH) level but increased the activities of
      superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and
      glutathione-S-transferase (GST) concomitantly with marked elevation in hydrogen
      peroxide (H2O2) and malondialdehyde (MDA) levels in liver and kidney of the
      treated groups compared with control. These findings suggest that undue exposure
      to 2,5-HD at environmentally relevant levels may impair liver and kidney
      functions through induction of oxidative stress. 

PMID- 25379040
TI  - Effects of Human Mesenchymal Stem Cells Isolated from Wharton's Jelly of the
      Umbilical Cord and Conditioned Media on Skeletal Muscle Regeneration Using a
      Myectomy Model.
AB  - Skeletal muscle has good regenerative capacity, but the extent of muscle injury
      and the developed fibrosis might prevent complete regeneration. The in vivo
      application of human mesenchymal stem cells (HMSCs) of the umbilical cord and the
      conditioned media (CM) where the HMSCs were cultured and expanded, associated
      with different vehicles to induce muscle regeneration, was evaluated in a rat
      myectomy model. Two commercially available vehicles and a spherical hydrogel
      developed by our research group were used. The treated groups obtained
      interesting results in terms of muscle regeneration, both in the histological and
      in the functional assessments. A less evident scar tissue, demonstrated by
      collagen type I quantification, was present in the muscles treated with HMSCs or
      their CM. In terms of the histological evaluation performed by ISO 10993-6
      scoring, it was observed that HMSCs apparently have a long-term negative effect,
      since the groups treated with CM presented better scores. CM could be considered
      an alternative to the in vivo transplantation of these cells, as it can benefit
      from the local tissue response to secreted molecules with similar results in
      terms of muscular regeneration. Searching for an optimal vehicle might be the key
      point in the future of skeletal muscle tissue engineering. 

PMID- 25379041
TI  - Phenotypic and proteomic characteristics of human dental pulp derived mesenchymal
      stem cells from a natal, an exfoliated deciduous, and an impacted third molar
      tooth.
AB  - The level of heterogeneity among the isolated stem cells makes them less valuable
      for clinical use. The purpose of this study was to understand the level of
      heterogeneity among human dental pulp derived mesenchymal stem cells by using
      basic cell biology and proteomic approaches. The cells were isolated from a natal
      (NDPSCs), an exfoliated deciduous (stem cells from human exfoliated deciduous
      (SHED)), and an impacted third molar (DPSCs) tooth of three different donors. All
      three stem cells displayed similar features related to morphology, proliferation
      rates, expression of various cell surface markers, and differentiation potentials
      into adipocytes, osteocytes, and chondrocytes. Furthermore, using 2DE approach
      coupled with MALDI-TOF/TOF, we have generated a common 2DE profile for all three
      stem cells. We found that 62.3 +/- 7% of the protein spots were conserved among
      the three mesenchymal stem cell lines. Sixty-one of these conserved spots were
      identified by MALDI-TOF/TOF analysis. Classification of the identified proteins
      based on biological function revealed that structurally important proteins and
      proteins that are involved in protein folding machinery are predominantly
      expressed by all three stem cell lines. Some of these proteins may hold
      importance in understanding specific properties of human dental pulp derived
      mesenchymal stem cells. 

PMID- 25379042
TI  - Adrenal and thyroid function in the fetus and preterm infant.
AB  - Adrenal and thyroid hormones are essential for the regulation of intrauterine
      homeostasis, and for the timely differentiation and maturation of fetal organs.
      These hormones play complex roles during fetal life, and are believed to underlie
      the cellular communication that coordinates maternal-fetal interactions. They
      serve to modulate the functional adaptation for extrauterine life during the
      perinatal period. The pathophysiology of systemic vasopressor-resistant
      hypotension is associated with low levels of circulating cortisol, a result of
      immaturity of hypothalamic-pituitary-adrenal axis in preterm infants under
      stress. Over the past few decades, studies in preterm infants have shown abnormal
      clinical findings that suggest adrenal or thyroid dysfunction, yet the criteria
      used to diagnose adrenal insufficiency in preterm infants continue to be
      arbitrary. In addition, although hypothyroidism is frequently observed in
      extremely low gestational age infants, the benefits of thyroid hormone
      replacement therapy remain controversial. Screening methods for congenital
      hypothyroidism or congenital adrenal hyperplasia in the preterm neonate are
      inconclusive. Thus, further understanding of fetal and perinatal adrenal and
      thyroid function will provide an insight into the management of adrenal and
      thyroid function in the preterm infant. 

PMID- 25379043
TI  - Advancements in the treatment of pediatric acute leukemia and brain tumor -
      continuous efforts for 100% cure.
AB  - Treatment outcomes of pediatric cancers have improved greatly with the
      development of improved treatment protocols, new drugs, and better supportive
      measures, resulting in overall survival rates greater than 70%. Survival rates
      are highest in acute lymphoblastic leukemia, reaching more than 90%, owing to
      risk-based treatment through multicenter clinical trials and protocols developed
      to prevent central nervous system relapse and testicular relapse in boys. New
      drugs including clofarabine and nelarabine are currently being evaluated in
      clinical trials, and other targeted agents are continuously being developed.
      Chimeric antigen receptor-modified T cells are now attracting interest for the
      treatment of recurrent or refractory disease. Stem cell transplantation is still
      the most effective treatment for pediatric acute myeloid leukemia (AML). However,
      in order to reduce treatment-related death after stem cell transplantation, there
      is need for improved treatments. New drugs and targeted agents are also needed
      for improved outcome of AML. Surgery and radiation therapy have been the mainstay
      for brain tumor treatment. However, chemotherapy is becoming more important for
      patients who are not eligible for radiotherapy owing to age. Stem cell transplant
      as a means of high dose chemotherapy and stem cell rescue is a new treatment
      modality and is often repeated for improved survival. Drugs such as temozolomide
      are new chemotherapeutic options. In order to achieve 100% cure in children with
      pediatric cancer, every possible treatment modality and effort should be
      considered. 

PMID- 25379044
TI  - Serum interleukin-1beta and tumor necrosis factor-alpha in febrile seizures: is
      there a link?
AB  - PURPOSE: Febrile seizures are induced by fever and are the most common type of
      seizures in children. Although numerous studies have been performed on febrile
      seizures, their pathophysiology remains unclear. Recent studies have shown that
      cytokines may play a role in the pathogenesis of febrile seizures. The present
      study was conducted to identify potential links between serum interleukin-1beta
      (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and febrile seizures.
      METHODS: Ninety-two patients with simple or complex febrile seizures (46 patients
      per seizure type), and 46 controls with comparable age, sex, and severity of
      temperature were enrolled. RESULTS: The median concentrations of serum IL-1beta
      in the simple, complex febrile seizure, and control groups were 0.05, 0.1, and
      0.67 pg/mL, respectively (P=0.001). Moreover, the median concentrations of TNF
      alpha in the simple, complex febrile seizure, and control groups were 2.5, 1, and
      61.5 pg/mL, respectively (P=0.001). Furthermore, there were significant
      differences between the case groups in serum IL-1beta and TNF-alpha levels
      (P<0.05). CONCLUSION: Unlike previous studies, our study does not support the
      hypothesis that increased IL-1beta and TNF-alpha production is involved in the
      pathogenesis of febrile seizures.

PMID- 25379045
TI  - The large-conductance calcium-activated potassium channel holds the key to the
      conundrum of familial hypokalemic periodic paralysis.
AB  - PURPOSE: Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant
      channelopathy characterized by episodic attacks of muscle weakness and
      hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium
      channel gene, SCN4A, have been found to be responsible for HOKPP; however, the
      mechanism that causes hypokalemia remains to be determined. The aim of this study
      was to improve the understanding of this mechanism by investigating the
      expression of calcium-activated potassium (KCa) channel genes in HOKPP patients.
      METHODS: We measured the intracellular calcium concentration with fura-2
      acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy
      individuals. We examined the mRNA and protein expression of KCa channel genes
      (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. RESULTS: Patient
      cells exhibited higher cytosolic calcium levels than normal cells. Quantitative
      reverse transcription polymerase chain reaction analysis showed that the mRNA
      levels of the KCa channel genes did not significantly differ between patient and
      normal cells. However, western blot analysis showed that protein levels of the
      KCNMA1 gene, which encodes KCa1.1 channels (also called big potassium channels),
      were significantly lower in the membrane fraction and higher in the cytosolic
      fraction of patient cells than normal cells. When patient cells were exposed to
      50 mM potassium buffer, which was used to induce depolarization, the altered
      subcellular distribution of BK channels remained unchanged. CONCLUSION: These
      findings suggest a novel mechanism for the development of hypokalemia and
      paralysis in HOKPP and demonstrate a connection between disease-associated
      mutations in calcium/sodium channels and pathogenic changes in nonmutant
      potassium channels.

PMID- 25379046
TI  - Serum procalcitonin as a diagnostic marker of neonatal sepsis.
AB  - PURPOSE: We evaluated serum procalcitonin (PCT) as a diagnostic marker of
      neonatal sepsis, and compared PCT levels with C-reactive protein (CRP) levels.
      METHODS: We retrospectively reviewed the medical records of 269 neonates with a
      suspected infection, admitted to Wonkwang University School of Medicine &
      Hospital between January 2011 and December 2012, for whom PCT and CRP values had
      been obtained. Neonates were categorized into 4 groups according to infection
      severity. CRP and PCT values were analyzed and compared, and their effectiveness
      as diagnostic markers was determined by using receiver operating characteristic
      (ROC) curve analysis. We also calculated the sensitivity, specificity, and
      positive, and negative predictive values. RESULTS: The mean PCT and CRP
      concentrations were respectively 56.27+/-81.89 and 71.14+/-37.17 mg/L in the
      "confirmed sepsis" group; 15.64+/-32.64 and 39.23+/-41.41 mg/L in the "suspected
      sepsis" group; 9.49+/-4.30 and 0.97+/-1.16 mg/L in the "mild infection" group;
      and 0.21+/-0.12 and 0.72+/-0.7 mg/L in the control group. High concentrations
      indicated greater severity of infection (P<0.001). Five of 18 patients with
      confirmed sepsis had low PCT levels (<1.0 mg/L) despite high CRP levels. In the
      ROC analysis, the area under the curve was 0.951 for CRP and 0.803 for PCT. The
      cutoff concentrations of 0.5 mg/L for PCT and 1.0 mg/L for CRP were optimal for
      diagnosing neonatal sepsis (sensitivity, 88.29% vs. 100%; specificity, 58.17% vs.
      85.66%; positive predictive value, 13.2% vs. 33.3%; negative predictive value,
      98.6% vs. 100%, respectively). CONCLUSION: PCT is a highly effective early
      diagnostic marker of neonatal infection. However, it may not be as reliable as
      CRP.

PMID- 25379047
TI  - Overlapping Guillain-Barre syndrome and Bickerstaff's brainstem encephalitis
      associated with Epstein Barr virus.
AB  - A flaccid tetraparesis in Bickerstaff's brainstem encephalitis (BBE) is presumed
      to be a sign of overlapping Guillain-Barre syndrome (GBS). In addition, BBE and
      Fisher syndrome, which are clinically similar and are both associated with the
      presence of the immunoglobulin G anti-GQ1b antibody, represent a specific
      autoimmune disease with a wide spectrum of symptoms that include ophthalmoplegia
      and ataxia. A 2-year-old boy presented with rapidly progressive ophthalmoplegia,
      ataxia, hyporeflexia, weakness of the lower extremities, and, subsequently,
      disturbance of consciousness. He experienced bronchitis with watery diarrhea and
      had laboratory evidence of recent infection with Epstein-Barr virus (EBV). He was
      diagnosed as having overlapping GBS and BBE associated with EBV and received
      treatment with a combination of immunoglobulin and methylprednisolone, as well as
      acyclovir, and had recovered completely after 3 months. In addition, he has not
      experienced any relapse over the past year. We suggest that combinations of
      symptoms and signs of central lesions (disturbance of consciousness) and
      peripheral lesions (ophthalmoplegia, facial weakness, limb weakness, and
      areflexia) are supportive of a diagnosis of overlapping GBS and BBE and can be
      helpful in achieving an early diagnosis, as well as for the administration of
      appropriate treatments. 

PMID- 25379048
TI  - Inhaled iloprost for the treatment of patient with Fontan circulation.
AB  - Decreased exercise capacity after Fontan surgery is relatively common and the
      failure of the Fontan state gradually increases with age. However, there is no
      further treatment for patients with Fontan circulation. Pulmonary vasodilation
      therapy is an effective method to solve this problem because pulmonary vascular
      resistance is a major factor of the Fontan problem. Inhaled iloprost is a
      chemically stable prostacyclin analogue and a potent pulmonary vasodilator. We
      experienced two cases of Fontan patients treated with inhaled iloprost for 12
      weeks. The first patient was an 18-year-old female with pulmonary atresia with an
      intact ventricular septum, and the second patient was a 22-year-old male with a
      double outlet right ventricle. Fifteen years have passed since both patients
      received Fontan surgery. While the pulmonary pressure was not decreased
      significantly, improved exercise capacity and cardiac output were observed
      without any major side effects in both patients. The iloprost inhalation therapy
      was well tolerated and effective for the symptomatic treatment of Fontan
      patients. 

PMID- 25379049
TI  - Cytomorphology of columnar cell variant of papillary carcinoma thyroid: A case
      report and review of the literature.
AB  - A 58 years old lady reported with history of progressively increasing lump in the
      neck. Patient had earlier undergone sub-total thyroidectomy (details not
      available) in a private institute one year back. Fine needle aspiration cytology
      (FNAC) of the present lump revealed features of papillary carcinoma thyroid.
      Patient subsequently underwent total thyroidectomy along with excision of a tumor
      nodule in the larynx. Gross examination of the specimen revealed a tumor nodule
      in the right lobe of the thyroid. Microscopic examination of the tumor nodule in
      the thyroid and larynx revealed a columnar cell variant of papillary carcinoma
      thyroid. Very few reports describing the cytomorphologic features of this variant
      of papillary carcinoma are available in the published literature. These reports
      highlight the absence or paucity of nuclear grooves and intranuclear inclusions
      in this variant. We describe a case of columnar cell variant of papillary
      carcinoma where nuclear grooves were prominently seen. In addition, we report the
      occurrence of rosette-like structures which were brought out better on FNA
      smears. These rosette-like structures have not been emphasized earlier in the
      published literature. The cytomorphologic features of this rare variant are also
      reviewed in this report. 

PMID- 25379050
TI  - Is fine needle aspiration cytology a useful diagnostic tool for granular cell
      tumors? A cytohistological review with emphasis on pitfalls.
AB  - BACKGROUND: Granular cell tumors (GCT) formerly known as Abrikossoff tumor or
      granular cell myoblastoma, are rare neoplasms encountered in the fine needle
      aspiration (FNA) service. Named because of their highly granular cytoplasm which
      is invariably positive for the S-100 antibody, the classic GCT is thought to be
      of neural origin. The cytomorphological features range from highly cellular to
      scanty cellular smears with dispersed polygonal tumor cells. The cells have
      abundant eosinophilic granular cytoplasm, eccentric round to oval vesicular
      nuclei with small inconspicuous nucleoli. The fragility of the cells can result
      in many stripped nuclei in a granular background. The differential diagnosis
      occasionally can range from a benign or reactive process to features that are
      suspicious for malignancy. Some of the concerning cytologic features include
      necrosis, mitoses and nuclear pleomorphism. METHODS: We identified 6 cases of
      suspected GCT on cytology within the last 10 years and compared them to their
      final histologic diagnoses. RESULTS: Four had histologic correlation of GCT
      including one case that was suspicious for GCT on cytology and called atypical
      with features concerning for a malignant neoplasm. Of the other two cases where
      GCT was suspected, one showed breast tissue with fibrocystic changes, and the
      other was a Hurthle cell adenoma of the thyroid. CONCLUSIONS: These results imply
      that FNA has utility in the diagnosis of GCT, and should be included in the
      differential diagnoses when cells with abundant granular cytoplasm are seen on
      cytology. Careful attention to cytologic atypia, signs of reactive changes, use
      of immunohistochemistry, and clinical correlation are helpful in arriving at a
      definite diagnosis on FNA cytology.

PMID- 25379051
TI  - Child and Caregiver Concordance of Potentially Traumatic Events Experienced by
      Orphaned and Abandoned Children.
AB  - Exposure to trauma is associated with significant emotional and behavioral
      difficulties among children (Perepletchikova & Kaufman, 2010). Overall, reports
      of trauma and violence experienced by children are discrepant from those of their
      caregivers (Lewis et al., 2012). Even less is known about the extent of
      concordance between orphans and their caregivers. This study examines the
      correlates of concordance in reported traumatic experiences between 1,269
      orphaned and abandoned children (OAC) and their caregivers. The OAC lived in
      family-settings in 5 low and middle income countries and were part of a
      longitudinal study, "Positive Outcomes for Orphans" (POFO) that enrolled children
      aged 6 to 12 at baseline. By examining concordance with respect to specific types
      of trauma reported, this study expands the understanding of who reports which
      types of traumas experienced by orphaned and abandoned children, thereby
      improving the potential to provide targeted interventions for children who have
      experienced such events. In this study, children and caregivers were asked
      separately if the child had experienced different types of potentially traumatic
      events. Children were significantly more likely to report physical abuse, sexual
      abuse and family violence than were caregivers. Caregivers were significantly
      more likely than children to report natural disasters and accidents. High levels
      of concordance were found in the reporting of wars, riots, killings, and deaths
      in the family. The impacts of trauma on behavior and mental health are profound,
      and highly effective interventions targeting sequelae of childhood trauma are
      currently being developed for use in low resource areas. Findings from this study
      demonstrate that it is feasible to conduct screening for potentially traumatic
      events utilizing child self-report in resource limited settings and that child
      self-report is crucial in evaluating trauma, particularly family violence and
      physical or sexual assault.

PMID- 25379052
TI  - Home visiting programs for HIV-affected families: a comparison of service quality
      between volunteer-driven and paraprofessional models.
AB  - Home visiting is a popular component of programs for HIV-affected children in sub
      Saharan Africa, but its implementation varies widely. While some home visitors
      are lay volunteers, other programs invest in more highly trained paraprofessional
      staff. This paper describes a study investigating whether additional investment
      in paraprofessional staffing translated into higher quality service delivery in
      one program context. Beneficiary children and caregivers at sites in KwaZulu
      Natal, South Africa were interviewed after 2 years of program enrollment and
      asked to report about their experiences with home visiting. Analysis focused on
      intervention exposure, including visit intensity, duration and the kinds of
      emotional, informational and tangible support provided. Few beneficiaries
      reported receiving home visits in program models primarily driven by lay
      volunteers; when visits did occur, they were shorter and more infrequent.
      Paraprofessional-driven programs not only provided significantly more home
      visits, but also provided greater interaction with the child, communication on a
      larger variety of topics, and more tangible support to caregivers. These results
      suggest that programs that invest in compensation and extensive training for home
      visitors are better able to serve and retain beneficiaries, and they support a
      move toward establishing a professional workforce of home visitors to support
      vulnerable children and families in South Africa.

PMID- 25379053
TI  - The subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3: dynamics and
      interdependence.
AB  - BACKGROUND: The S-phase checkpoint aims to prevent cells from generation of
      extensive single-stranded DNA that predisposes to genome instability. The S.
      cerevisiae complex Tof1/Csm3/Mrc1 acts to restrain the replicative MCM helicase
      when DNA synthesis is prohibited. Keeping the replication machinery intact allows
      restart of the replication fork when the block is relieved. Although the subunits
      of the Tof1/Csm3/Mrc1 complex are well studied, the impact of every single
      subunit on the triple complex formation and function needs to be established.
      FINDINGS: This work studies the cellular localization and the chromatin binding
      of GFP-tagged subunits when the complex is intact and when a subunit is missing.
      We demonstrate that the complex is formed in cell nucleus, not the cytoplasm, as
      Tof1, Csm3 and Mrc1 enter the nucleus independently from one another. Via in situ
      chromatin binding assay we show that a Tof1-Csm3 dimer formation and chromatin
      binding is required to ensure the attachment of Mrc1 to chromatin. Our study
      indicates that the translocation into the nucleus is not the process to regulate
      the timing of chromatin association of Mrc1. We also studied the nuclear behavior
      of Mrc1 subunit in the process of adaptation to the presence hydroxyurea. Our
      results indicate that after prolonged HU incubation, cells bypass the S-phase
      checkpoint and proceed throughout the cell cycle. This process is accompanied by
      Mrc1 chromatin detachment and Rad53 dephosphorylation. CONCLUSIONS: In S.
      cerevisiae the subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3
      independently enter the cell nucleus, where a Tof1-Csm3 dimer is formed to ensure
      the chromatin binding of Mrc1 and favor DNA replication and S-phase checkpoint
      fork arrest. In the process of adaptation to the presence of hydroxyurea Mrc1 is
      detached from chromatin and Rad53 checkpoint activity is diminished in order to
      allow S-phase checkpoint escape and completion of the cell cycle.

PMID- 25379054
TI  - Capturing the response of Clostridium acetobutylicum to chemical stressors using
      a regulated genome-scale metabolic model.
AB  - BACKGROUND: Clostridia are anaerobic Gram-positive Firmicutes containing broad
      and flexible systems for substrate utilization, which have been used successfully
      to produce a range of industrial compounds. In particular, Clostridium
      acetobutylicum has been used to produce butanol on an industrial scale through
      acetone-butanol-ethanol (ABE) fermentation. A genome-scale metabolic (GSM) model
      is a powerful tool for understanding the metabolic capacities of an organism and
      developing metabolic engineering strategies for strain development. The
      integration of stress-related specific transcriptomics information with the GSM
      model provides opportunities for elucidating the focal points of regulation.
      RESULTS: We describe here the construction and validation of a GSM model for C.
      acetobutylicum ATCC 824, iCac802. iCac802 spans 802 genes and includes 1,137
      metabolites and 1,462 reactions, along with gene-protein-reaction associations.
      Both (13)C-MFA and gene deletion data in the ABE fermentation pathway were used
      to test the predicted flux ranges allowed by the model. We also describe the
      CoreReg method, introduced in this paper, to integrate transcriptomic data and
      identify core sets of reactions that, when their flux was selectively restricted,
      reproduced flux and biomass-formation ranges seen under all regulatory
      constraints. CoreReg was used in response to butanol and butyrate stress to
      tighten bounds for 50 reactions within the iCac802 model. These bounds affected
      the flux of tens of reactions in core metabolism. The model, incorporating the
      regulatory restrictions from CoreReg under chemical stress, exhibited an
      approximate 70% reduction in biomass yield for most stress conditions.
      CONCLUSIONS: The regulation placed on the model for the two stresses using
      CoreReg identified differences in the respective responses, including distinct
      core sets and the restriction of biomass production similar to experimental
      observations. Given the core sets predicted by the CoreReg method, remedial
      actions can be taken to counteract the effect of stress on metabolism. For less
      well-known systems, plausible regulatory loops can be suggested around the
      affected metabolic reactions, and the hypotheses can be tested experimentally.

PMID- 25379056
TI  - Glucose and lipid assessment in patients with acute stroke.
AB  - BACKGROUND: Stroke is a major health issue in Nigeria and it is also a common
      cause of emergency admissions. Stroke often results in increased morbidity,
      mortality and reduced quality of life in people thus affected. The risk factors
      for stroke include metabolic abnormalities such as dyslipidaemia and diabetes
      mellitus (DM). The stress of an acute stroke may present with hyperglycaemia and
      in persons without a prior history of DM, may be a pointer to stress
      hyperglycaemia or undiagnosed DM. METHODOLOGY: This was a cross sectional study
      carried out over a period of one year in a teaching hospital in Lagos, Nigeria.
      Patients with acute stroke admitted to the hospital within three days of the
      episode of stroke and who met other inclusion criteria for the Study were
      consecutively recruited. Clinically relevant data was documented and biochemical
      assessments were carried out within three days of hospitalization. Tests for
      lipid profile, glycosylated haemoglobin(HbA1c), and blood glucose at presentation
      were carried out. The presence of past history of DM, undiagnosed DM, stress
      hyperglycaemia and abnormal lipid profile were noted. Students t test and Chi
      square were the statistical tests employed. RESULTS: A total of 137 persons with
      stroke were recruited of which 107 (76%) met the defining criteria for ischaemic
      stroke. The mean age and age range of the Study subjects were 62.2 (11.7) and 26
      89 years respectively. The Study subjects were classified according to their
      glycaemic status into the following categories viz; stress hyperglycaemia,
      euglycaemia, DM and previously undiagnosed DM. Stress hyperglycaemia occurred
      commonly in the fifth decade of life and its incidence was comparable between
      those with cerebral and haemorrhagic stroke. The commonly occurring lipid
      abnormalities were elevated LDL-C and low HDL. CONCLUSIONS: The detection of
      abnormal metabolic milieu is a window of opportunity for aggressive management in
      persons with stroke as this will improve outcome. Routine screening for
      hyperglycaemia in persons with stroke using glycosylated haemoglobin tests and
      blood glucose may uncover previously undiagnosed DM.

PMID- 25379055
TI  - The exometabolome of Clostridium thermocellum reveals overflow metabolism at high
      cellulose loading.
AB  - BACKGROUND: Clostridium thermocellum is a model thermophilic organism for the
      production of biofuels from lignocellulosic substrates. The majority of
      publications studying the physiology of this organism use substrate
      concentrations of <=10 g/L. However, industrially relevant concentrations of
      substrate start at 100 g/L carbohydrate, which corresponds to approximately 150
      g/L solids. To gain insight into the physiology of fermentation of high substrate
      concentrations, we studied the growth on, and utilization of high concentrations
      of crystalline cellulose varying from 50 to 100 g/L by C. thermocellum. RESULTS:
      Using a defined medium, batch cultures of C. thermocellum achieved 93% conversion
      of cellulose (Avicel) initially present at 100 g/L. The maximum rate of substrate
      utilization increased with increasing substrate loading. During fermentation of
      100 g/L cellulose, growth ceased when about half of the substrate had been
      solubilized. However, fermentation continued in an uncoupled mode until substrate
      utilization was almost complete. In addition to commonly reported fermentation
      products, amino acids - predominantly L-valine and L-alanine - were secreted at
      concentrations up to 7.5 g/L. Uncoupled metabolism was also accompanied by
      products not documented previously for C. thermocellum, including isobutanol,
      meso- and RR/SS-2,3-butanediol and trace amounts of 3-methyl-1-butanol, 2-methyl
      1-butanol and 1-propanol. We hypothesize that C. thermocellum uses overflow
      metabolism to balance its metabolism around the pyruvate node in glycolysis.
      CONCLUSIONS: C. thermocellum is able to utilize industrially relevant
      concentrations of cellulose, up to 93 g/L. We report here one of the highest
      degrees of crystalline cellulose utilization observed thus far for a pure culture
      of C. thermocellum, the highest maximum substrate utilization rate and the
      highest amount of isobutanol produced by a wild-type organism.

PMID- 25379057
TI  - Testosterone, HDL and cardiovascular risk in men: the jury is still out.
AB  - "Even when reductions in HDL-cholesterol are observed as a consequence of
      androgen therapy, the implications for cardiovascular risk modification remain
      highly uncertain."

PMID- 25379058
TI  - El Nino and health risks from landscape fire emissions in Southeast Asia.
AB  - Emissions from landscape fires affect both climate and air quality1. In this
      study, we combine satellite-derived fire estimates and atmospheric modeling to
      quantify health effects from fire emissions in Southeast Asia from 1997 to 2006.
      This region has large interannual variability in fire activity due to coupling
      between El Nino-induced droughts and anthropogenic land use change2,3. We show
      that during strong El Nino years, fires contribute up to 200 MUg/m3 and 50 ppb in
      annual average fine particulate matter (PM2.5) and ozone (O3) surface
      concentrations near fire sources, respectively. This corresponds to a fire
      contribution of 200 additional days per year that exceed the World Health
      Organization (WHO) 50 MUg/m3 24-hour PM2.5 interim target (IT-2)4 and an
      estimated 10,800 (6,800-14,300) person (~2%) annual increase in regional adult
      cardiovascular mortality. Our results indicate that reducing regional
      deforestation and degradation fires would improve public health along with widely
      established benefits from reducing carbon emissions, preserving biodiversity, and
      maintaining ecosystem services.

PMID- 25379059
TI  - Empirical evaluation of meta-analytic approaches for nutrient and health outcome
      dose-response data.
AB  - The objective of this study is to empirically compare alternative meta-analytic
      methods for combining dose-response data from epidemiological studies. We
      identified meta-analyses of epidemiological studies that analyzed the association
      between a single nutrient and a dichotomous outcome. For each topic, we performed
      meta-analyses of odds ratios with five approaches: using extreme exposure
      categories only, two-step approach (first calculated study-specific effects then
      combined across studies) using unadjusted data, two-step approach using adjusted
      data, one-step approach (analyzed all data in one regression model) using
      unadjusted data, and one-step approach using adjusted data. Meta-analyses
      including only extreme exposure categories gave consistently bigger effects and
      wider confidence intervals than meta-analyses using all data. Confidence
      intervals of effect sizes were generally wider in meta-analyses with the two-step
      approach, compared with the one-step approach. Meta-analyses using unadjusted
      data and adjusted data differed, with no consistent pattern of discordance in
      direction, statistical significance, or magnitude of effect. We discourage using
      meta-analysis approaches that only use data from extreme exposure categories. The
      one-step approach generally has higher precision than the two-step approach.
      Sensitivity analysis comparing results between meta-analyses of adjusted and
      unadjusted data may be useful in indicating the presence of confounding.

PMID- 25379060
TI  - A study of acute otitis externa at Wellington Hospital, 2007-2011.
AB  - BACKGROUND: Acute otitis externa (AOE) is a common inflammatory condition
      affecting the external ear that occasionally presents with persistent, severe
      pain, which may be unresponsive to first-line therapy and require assessment and
      treatment in the hospital setting. AIMS: To identify the microorganisms
      responsible for cases of otitis externa presenting to Wellington Hospital, New
      Zealand, over a five-year period between 2007 and 2011. We also aim to evaluate
      current management of this condition and to recommend future treatment options.
      METHOD: A five-year retrospective study, with data obtained from case notes and
      electronic records for all patients presenting with otitis externa to Wellington
      Hospital between 2007 and 2011. RESULTS: Of three hundred and forty-seven cases
      identified, 144 were included in the study. Pseudomonas aeruginosa (P.
      aeruginosa) was the most common organism (46.5 per cent), while Staphylococcus
      aureus (S. aureus) was the second most common (31.9 per cent). Most patients
      received appropriate topical treatment. However, a significant number were
      treated with systemic antibiotics alone without adverse outcomes. CONCLUSION:
      Pseudomonas aeruginosa is the most common microbe causing acute otitis externa in
      patients that require hospital level management in Wellington, New Zealand. In
      most cases, patients received appropriate topical therapy; however, it appears a
      large number received systemic antibiotic therapy without topical treatment. We
      recommend broad-spectrum topical antimicrobial therapy in all patients with
      uncomplicated AOE and culture-sensitive topical treatment with consideration of
      systemic antimicrobials for severe AOE requiring hospital admission.

PMID- 25379061
TI  - Miliary tuberculosis with left brachial monoplegia: A case report.
AB  - Tuberculoma of the brain is a major neurological problem in developing countries
      accounting for 12 to 30 per cent of all intracranial masses. It often presents
      with focal neurological symptoms or seizures. Simultaneous occurrence of brain
      tuberculoma with miliary mottling in the lungs is uncommon in the immunocompetent
      patient. We report only the second case of monoplegia and miliary tuberculosis,
      wherein the patient presented with acute onset left brachial monoplegia, upper
      motor neuron facial palsy, and fever with an MRI of the brain showing multiple
      granulomas and chest x-ray showing miliary mottling. The patient's neurological
      deficit started to resolve with corticosteroids and anti-tubercular treatment. 

PMID- 25379062
TI  - SGLT2 inhibitors: New medicines for addressing unmet needs in type 2 diabetes.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) is rising in Australia. Sodium
      glucose co-transporter 2 (SGLT2) inhibitors are an emerging treatment for T2DM.
      SGLT2 inhibitors offer a novel approach to lowering hyperglycaemia by suppressing
      renal glucose reabsorption and increasing urinary glucose excretion. The
      increased urinary glucose excretion has also been associated with caloric loss
      and osmotic diuresis. Dapagliflozin and canagliflozin are the SGLT2 inhibitors
      that are approved for clinical use in the US, the European Union (EU), and
      Australia. Their use results in reductions in HbA1c and body weight across a
      broad range of patient populations ranging from drug-naive patients to those who
      require additional therapy due to inadequate glycaemic control on their existing
      treatment. In addition, reductions in blood pressure (BP), particularly systolic
      BP, have also been noted. SGLT2 inhibitors are generally well tolerated with low
      rates of adverse events. Episodes of hypoglycaemia were mostly classified as
      minor, with low and balanced rates of severe hypoglycaemia across studies. The
      proportions of patients with genital infections and urinary tract infections were
      higher with dapagliflozin and canagliflozin versus their comparators. However,
      these infections were generally mild-to-moderate in intensity, treated with
      standard antimicrobial therapies, and rarely led to discontinuation. No dosage
      adjustments for dapagliflozin and canagliflozin are recommended for normal-to
      mild renal impairment. Dapagliflozin and canagliflozin are not recommended for
      use in patients with eGFR<60 and <45mL/min/1.73m(2), respectively. Overall, SGLT2
      inhibitors have shown the potential to become an important addition to the
      treatment armamentarium for effective management of patients with T2DM. 

PMID- 25379063
TI  - Jejuno-jejunal intussusception: An unusual presentation of malignant melanoma.
AB  - Jejuno-jejunal intussusception is a rare mode of metastatic melanoma
      presentation, with only six cases being reported in the English medical
      literature to date. We present a case of a 55-year-old female who presented to us
      with features of obstruction. On exploration, it was discovered that she had
      jejuno-jejunal intussusception, with enlarged blackened mesenteric lymph nodes.
      Resection and anastomosis were performed. On further histopathological
      examination, a lesion was found to be a metastatic malignant melanoma. 

PMID- 25379064
TI  - An unorthodox innervation of the gluteus maximus muscle and other associated
      variations: A case report.
AB  - Knowledge of peripheral nerve morphology, location, and variation is important
      for facilitating appropriate diagnosis and intervention. We present a unique case
      of absence of the inferior gluteal nerve and high division of the sciatic nerve.
      In this instance, the common peroneal nerve was found piercing the piriformis
      muscle and emerging distally in the form of two trunks: thin medial and thick
      lateral. The medial trunk presented an interesting course, supplying the gluteus
      maximus muscle before joining the lateral trunk to form the common peroneal
      nerve. Additionally, the arteria nervi ischiadisci was also observed accompanying
      and supplying the tibial nerve passing inferior to the piriformis. These
      variations are important for clinicians and surgeons for some radiological
      diagnoses and surgical procedures in the lower limb. 

PMID- 25379065
TI  - Social media and the future of medicine.

PMID- 25379067
TI  - Increasing severity of aortic atherosclerosis in coronary artery bypass grafting
      patients evaluated by transesophageal echocardiography.
AB  - BACKGROUND: Atherosclerotic disease in coronary artery bypass grafting (CABG)
      patients is a potential contributor to complications in the perioperative
      periods. This study was undertaken to better define how the frequency of aortic
      atheromatous disease among patients coming for CABG has evolved over the last
      decade. METHODS: Data from elective patients coming for CABG who underwent
      transesophageal echocardiography (TEE) examinations following induction of
      anesthesia were obtained for the years 2002 and 2009. Aortas were graded
      according to the method of Kronzon, with the following interpretations: normal =
      grade I, intimal thickening = 2, atheroma of less than 5 mm = 3, atheroma of > 5
      mm = 4, and any mobile atheroma = 5. The data of 124 patients who underwent
      comprehensive exam of the aorta by one cardiac anesthesiologist were gathered and
      assigned into two groups based on the year TEE was done. Student's t-test was
      used for statistical analysis. A P value < 0.05 was considered significant. The
      data were presented as mean +/- SD. RESULTS: There was significant difference
      between group 2002 (2.05 +/- 1.28) and group 2009 (2.59 +/- 1.11) in atheroma
      grade (P = 0.013). CONCLUSIONS: Patients coming for CABG in group 2009 exhibited
      significantly higher grades of aortic atheroma on TEE, compared to group 2002.
      Understanding the risk of atheroma in the elderly CABG population may help in
      altering surgical approaches to lessen the risk of catastrophic stroke. Potential
      options needing further study include the off-pump approach and modification of
      cross-clamp site and technique as well as other modalities.

PMID- 25379066
TI  - Ethanol pharmacokinetics in neonates and infants.
AB  - INTRODUCTION: Ethanol has been used for years in neonatal and infant liquid
      medications, yet the pharmacokinetics, pharmacodynamics, and safety of ethanol in
      this vulnerable population have not been well characterized. The purpose of this
      review is to raise awareness of ethanol use as an excipient in neonatal and
      infant medications and to provide insight, based on the available evidence, into
      clearance rates of ethanol in babies. We also discuss ethanol pharmacokinetics in
      adults, theoretical pharmacokinetic changes in neonates and infants as it may
      apply to ethanol disposition, and case reports involving ethanol exposure in
      neonates and infants. MATERIALS AND METHODS: This study was a narrative review in
      which relevant papers were selected using databases and scientific search engines
      such as PubMed with the key words ethanol, infant, and newborn infant. RESULTS:
      It remains unclear what ethanol exposure is safe for neonates and infants. The
      Food and Drug Administration and American Academy of Pediatrics have both taken
      action, by either setting limits of ethanol content in over-the-counter
      medications or by recommending restricted exposure to ethanol-containing
      pediatric formulations. CONCLUSIONS: Until the short- and long-term health
      effects of chronic ethanol administration can be further characterized, ethanol
      containing medications should be used with caution.

PMID- 25379068
TI  - Arrest History and Intimate Partner Violence Perpetration in a Sample of Men and
      Women Arrested for Domestic Violence.
AB  - Intimate partner violence (IPV) is a serious and prevalent problem throughout the
      United States. Currently, individuals arrested for domestic violence are often
      court mandated to batterer intervention programs (BIPs). However, little is known
      about the arrest histories of these individuals, especially women. The current
      study examined the arrest histories of men (n = 303) and women (n = 82) arrested
      for domestic violence and court-referred to BIPs. Results demonstrated that over
      30% of the entire sample had been previously arrested for a non-violent offense,
      and over 25% of the participants had been previously arrested for a violent
      offense other than domestic violence. Moreover, men were arrested significantly
      more frequently for violence-related and non-violent offenses than their female
      counterparts. In addition, men were more likely than women to have consumed binge
      levels of alcohol prior to the offense that led to their most recent arrest and
      court-referral to a BIP. Lastly, arrest history was positively associated with
      physical and psychological aggression perpetration against an intimate partner
      for men only, such that more previous arrests were associated with more frequent
      aggression. These results provide evidence that many men and women arrested for
      domestic violence have engaged in a number of diverse criminal acts during their
      lifetimes, suggesting that BIPs may need to address general criminal behavior.

PMID- 25379069
TI  - An electrostatic microwell-based biochip for phytoplanktonic cell trapping.
AB  - A simple microwell-based microfluidic chip for microalgal cells trapping was
      fabricated. An electrostaticcell trapping mechanism, enabled by a positively
      charged glass surface, was used. The chip was capable of capturing multiple algal
      cell types. In the case of filamentous Spirulina platensis, we observed single
      filament occupancy of up to ~30% available wells, as high as some previously
      proposed methods. Captured filaments were not of any preferential size,
      suggesting well randomized cell trapping. It was found that the electrostatic
      attraction did not affect the cell growth. Total replacement of liquid inside the
      wells could be achieved by pumping new solutions via the inlet, making single
      cell experiments in controlled chemical conditions possible. After the top layer
      of the chip was removed, cells in the wells could be simply transferred using a
      micropipette, turning the chip into a platform for strain selection. 

PMID- 25379070
TI  - Deformation of red blood cells using acoustic radiation forces.
AB  - Acoustic radiation forces have been used to manipulate cells and bacteria in a
      number of recent microfluidic applications. The net force on a cell has been
      subject to careful investigation over a number of decades. We demonstrate that
      the radiation forces also act to deformcells. An ultrasonic standing wave field
      is created in a 0.1 mm glass capillary at a frequency of 7.9 MHz. Using
      osmotically swollen red-blood cells, we show observable deformations up to an
      aspect ratio of 1.35, comparable to deformations created by optical tweezing. In
      contrast to optical technologies, ultrasonic devices are potentially capable of
      deforming thousands of cells simultaneously. We create a finite element model
      that includes both the acoustic environment of the cell, and a model of the cell
      membrane subject to forces resulting from the non-linear aspects of the acoustic
      field. The model is found to give reasonable agreement with the experimental
      results, and shows that the deformation is the result of variation in an acoustic
      force that is directed outwards at all points on the cell membrane. We foresee
      applications in diagnostic devices, and in the possibility of mechanically
      stimulating cells to promote differentiation and physiological effects. 

PMID- 25379071
TI  - Mathematical and numerical model to study two-dimensional free flow isoelectric
      focusing.
AB  - Even though isoelectric focusing (IEF) is a very useful technique for sample
      concentration and separation, it is challenging to extract separated samples for
      further processing. Moreover, the continuous sample concentration and separation
      are not possible in the conventional IEF. To overcome these challenges, free flow
      IEF (FFIEF) is introduced in which a flow field is applied in the direction
      perpendicular to the applied electric field. In this study, a mathematical model
      is developed for FFIEF to understand the roles of flow and electric fields for
      efficient design of microfluidic chip for continuous separation of proteins from
      an initial well mixed solution. A finite volume based numerical scheme is
      implemented to simulate two dimensional FFIEF in a microfluidic chip. Simulation
      results indicate that a pH gradient forms as samples flow downstream and this pH
      profile agrees well with experimental results validating our model. In addition,
      our simulation results predict the experimental behavior of pI markers in a FFIEF
      microchip. This numerical model is used to predict the separation behavior of two
      proteins (serum albumin and cardiac troponin I) in a two-dimensional straight
      microchip. The effect of electric field is investigated for continuous separation
      of proteins. Moreover, a new channel design is presented to increase the
      separation resolution by introducing cross-stream flow velocity. Numerical
      results indicate that the separation resolution can be improved by three folds in
      this new design compare to the conventional straight channel design. 

PMID- 25379072
TI  - Versatile on-demand droplet generation for controlled encapsulation.
AB  - We present a droplet-based microfluidic system for performing bioassays requiring
      controlled analyte encapsulation by employing highly flexible on-demand droplet
      generation. On-demand droplet generation and encapsulation are achieved
      pneumatically using a microdispensing pump connected to a constant pressure
      source. The system generates single droplets to the collection route only when
      the pump is actuated with a designated pressure level and produces two-phase
      parallel flow to the waste route during the stand-by state. We analyzed the
      effect of actuation pressure on the stability and size of droplets and optimized
      conditions for generation of stable droplets over a wide pressure range. By
      increasing the duration of pump actuation, we could either trigger a short train
      of identical size droplets or generate a single larger droplet. We also
      investigated the methodology to control droplet contents by fine-tuning flow
      rates or implementing a resistance bridge between the pump and main channels. We
      demonstrated the integrated chip for on-demand mixing between two aqueous phases
      in droplets and on-demand encapsulation of Escherichia coli cells. Our unique on
      demand feature for selective encapsulation is particularly appropriate for
      bioassays with extremely dilute samples, such as pathogens in a clinical sample,
      since it can significantly reduce the number of empty droplets that impede
      droplet collection and subsequent data analysis. 

PMID- 25379074
TI  - Isolation of cells for selective treatment and analysis using a magnetic
      microfluidic chip.
AB  - This study describes the development and testing of a magnetic microfluidic chip
      (MMC) for trapping and isolating cells tagged with superparamagnetic beads (SPBs)
      in a microfluidic environment for selective treatment and analysis. The trapping
      and isolation are done in two separate steps; first, the trapping of the tagged
      cells in a main channel is achieved by soft ferromagnetic disks and second, the
      transportation of the cells into side chambers for isolation is executed by
      tapered conductive paths made of Gold (Au). Numerical simulations were performed
      to analyze the magnetic flux and force distributions of the disks and conducting
      paths, for trapping and transporting SPBs. The MMC was fabricated using standard
      microfabrication processes. Experiments were performed with E. coli (K12 strand)
      tagged with 2.8 MUm SPBs. The results showed that E. coli can be separated from a
      sample solution by trapping them at the disk sites, and then isolated into
      chambers by transporting them along the tapered conducting paths. Once the E.
      coli was trapped inside the side chambers, two selective treatments were
      performed. In one chamber, a solution with minimal nutrition content was added
      and, in another chamber, a solution with essential nutrition was added. The
      results showed that the growth of bacteria cultured in the second chamber
      containing nutrient was significantly higher, demonstrating that the E. coli was
      not affected by the magnetically driven transportation and the feasibility of
      performing different treatments on selectively isolated cells on a single
      microfluidic platform. 

PMID- 25379073
TI  - Probing transient protein-mediated DNA linkages using nanoconfinement.
AB  - We present an analytic technique for probing protein-catalyzed transient DNA
      loops that is based on nanofluidic channels. In these nanochannels, DNA is forced
      in a linear configuration that makes loops appear as folds whose size can easily
      be quantified. Using this technique, we study the interaction between T4 DNA
      ligase and DNA. We find that T4 DNA ligase binding changes the physical
      characteristics of the DNApolymer, in particular persistence length and effective
      width. We find that the rate of DNA fold unrolling is significantly reduced when
      T4 DNA ligase and ATP are applied to bare DNA. Together with evidence of T4 DNA
      ligase bridging two different segments of DNA based on AFM imaging, we thus
      conclude that ligase can transiently stabilize folded DNA configurations by
      coordinating genetically distant DNA stretches. 

PMID- 25379075
TI  - Tilted post arrays for separating long DNA.
AB  - Recent simulations by Chen and Dorfman [Electrophoresis 35, 405-411 (2014)]
      suggested that "tilting" the electric field with respect to the lattice vectors
      of a hexagonal post array would lead to a substantial improvement in
      electrophoretic DNA separations therein. We constructed such an array where the
      electric field is applied at an angle equidistant between the two lattice
      vectors. This tilted array leads to (i) baseline resolution of 20 kbp DNA and
      lambda DNA (48.5 kbp) in a 4 mm channel and (ii) measurable separation
      resolutions for electric fields up to 50 V/cm, both of which are improvements
      over untilted post arrays of the same post density. The predicted time required
      to reach a resolution of unity is approximately 5 min, independent of electric
      field. The separations are more reproducible at higher fields. 

PMID- 25379076
TI  - Modeling and validation of autoinducer-mediated bacterial gene expression in
      microfluidic environments.
AB  - Biosensors exploiting communication within genetically engineered bacteria are
      becoming increasingly important for monitoring environmental changes. Currently,
      there are a variety of mathematical models for understanding and predicting how
      genetically engineered bacteria respond to molecular stimuli in these
      environments, but as sensors have miniaturized towards microfluidics and are
      subjected to complex time-varying inputs, the shortcomings of these models have
      become apparent. The effects of microfluidic environments such as low oxygen
      concentration, increased biofilm encapsulation, diffusion limited molecular
      distribution, and higher population densities strongly affect rate constants for
      gene expression not accounted for in previous models. We report a mathematical
      model that accurately predicts the biological response of the autoinducer N-acyl
      homoserine lactone-mediated green fluorescent protein expression in reporter
      bacteria in microfluidic environments by accommodating these rate constants. This
      generalized mass action model considers a chain of biomolecular events from input
      autoinducer chemical to fluorescent protein expression through a series of six
      chemical species. We have validated this model against experimental data from our
      own apparatus as well as prior published experimental results. Results indicate
      accurate prediction of dynamics (e.g., 14% peak time error from a pulse input)
      and with reduced mean-squared error with pulse or step inputs for a range of
      concentrations (10 MUM-30 MUM). This model can help advance the design of
      genetically engineered bacteria sensors and molecular communication devices. 

PMID- 25379077
TI  - Dean flow-coupled inertial focusing in curved channels.
AB  - Passive particle focusing based on inertial microfluidics was recently introduced
      as a high-throughput alternative to active focusing methods that require an
      external force field to manipulate particles. In inertial microfluidics, dominant
      inertial forces cause particles to move across streamlines and occupy equilibrium
      positions along the faces of walls in flows through straight micro channels. In
      this study, we systematically analyzed the addition of secondary Dean forces by
      introducing curvature and show how randomly distributed particles entering a
      simple u-shaped curved channel are focused to a fixed lateral position exiting
      the curvature. We found the lateral particle focusing position to be fixed and
      largely independent of radius of curvature and whether particles entering the
      curvature are pre-focused (at equilibrium) or randomly distributed. Unlike
      focusing in straight channels, where focusing typically is limited to channel
      cross-sections in the range of particle size to create single focusing point, we
      report here particle focusing in a large cross-section area (channel aspect ratio
      1:10). Furthermore, we describe a simple u-shaped curved channel, with single
      inlet and four outlets, for filtration applications. We demonstrate continuous
      focusing and filtration of 10 MUm particles (with >90% filtration efficiency)
      from a suspension mixture at throughputs several orders of magnitude higher than
      flow through straight channels (volume flow rate of 4.25 ml/min). Finally, as an
      example of high throughput cell processing application, white blood cells were
      continuously processed with a filtration efficiency of 78% with maintained high
      viability. We expect the study will aid in the fundamental understanding of flow
      through curved channels and open the door for the development of a whole set of
      bio-analytical applications. 

PMID- 25379078
TI  - Coalescing drops in microfluidic parking networks: A multifunctional platform for
      drop-based microfluidics.
AB  - Multiwell plate and pipette systems have revolutionized modern biological
      analysis; however, they have disadvantages because testing in the submicroliter
      range is challenging, and increasing the number of samples is expensive. We
      propose a new microfluidic methodology that delivers the functionality of
      multiwell plates and pipettes at the nanoliter scale by utilizing drop
      coalescence and confinement-guided breakup in microfluidic parking networks
      (MPNs). Highly monodisperse arrays of drops obtained using a hydrodynamic self
      rectification process are parked at prescribed locations in the device, and our
      method allows subsequent drop manipulations such as fine-gradation dilutions,
      reactant addition, and fluid replacement while retaining microparticles contained
      in the sample. Our devices operate in a quasistatic regime where drop shapes are
      determined primarily by the channel geometry. Thus, the behavior of parked drops
      is insensitive to flow conditions. This insensitivity enables highly parallelized
      manipulation of drop arrays of different composition, without a need for fine
      tuning the flow conditions and other system parameters. We also find that drop
      coalescence can be switched off above a critical capillary number, enabling
      individual addressability of drops in complex MPNs. The platform demonstrated
      here is a promising candidate for conducting multistep biological assays in a
      highly multiplexed manner, using thousands of submicroliter samples. 

PMID- 25379079
TI  - Microfluidic sterilization.
AB  - Nowadays, microfluidics is attracting more and more attentions in the biological
      society and has provided powerful solutions for various applications. This paper
      reported a microfluidic strategy for aqueous sample sterilization. A well
      designed small microchannel with a high hydrodynamic resistance was used to
      function as an in-chip pressure regulator. The pressure in the upstream
      microchannel was thereby elevated which made it possible to maintain a boiling
      free high temperature environment for aqueous sample sterilization. A 120 
      degrees C temperature along with a pressure of 400 kPa was successfully achieved
      inside the chip to sterilize aqueous samples with E. coli and Staphylococcus
      aureus inside. This technique will find wide applications in portable cell
      culturing, microsurgery in wild fields, and other related micro total analysis
      systems. 

PMID- 25379080
TI  - Stable chemical bonding of porous membranes and poly(dimethylsiloxane) devices
      for long-term cell culture.
AB  - We have investigated the bonding stability of various silane treatments for the
      integration of track-etched membranes with poly(dimethylsiloxane) (PDMS)
      microfluidic devices. We compare various treatments using trialkoxysilanes or
      dipodal silanes to determine the effect of the organofunctional group, cross-link
      density, reaction solvent, and catalyst on the bond stability. We find that
      devices made using existing silane methods delaminated after one day when
      immersed in cell culture medium at 37  degrees C. In contrast, the dipodal
      silane, bis[3-(trimethoxysilyl)propyl]amine, is shown to yield stable and
      functional integration of membranes with PDMS that is suitable for long-term cell
      culture. To demonstrate application of the technique, we fabricated an open
      surface device in which cells cultured on a track-etched membrane can be
      stimulated at their basal side via embedded microfluidic channels. C2C12 mouse
      myoblasts were differentiated into myotubes over the course of two weeks on these
      devices to demonstrate biocompatibility. Finally, devices were imaged during the
      basal-side delivery of a fluorescent stain to validate the membrane operation and
      long-term stability of the bonding technique. 

PMID- 25379081
TI  - Magnetographic array for the capture and enumeration of single cells and cell
      pairs.
AB  - We present a simple microchip device consisting of an overlaid pattern of
      micromagnets and microwells capable of capturing magnetically labeled cells into
      well-defined compartments (with accuracies >95%). Its flexible design permits the
      programmable deposition of single cells for their direct enumeration and pairs of
      cells for the detailed analysis of cell-cell interactions. This cell arraying
      device requires no external power and can be operated solely with permanent
      magnets. Large scale image analysis of cells captured in this array can yield
      valuable information (e.g., regarding various immune parameters such as the
      CD4:CD8 ratio) in a miniaturized and portable platform. 

PMID- 25379082
TI  - A high-throughput cellulase screening system based on droplet microfluidics.
AB  - A new ultra-high-throughput screening assay for the detection of cellulase
      activity was developed based on microfluidic sorting. Cellulase activity is
      detected using a series of coupled enzymes leading to the formation of a
      fluorescent product that can be detected on a chip. Using this method, we have
      achieved up to 300-fold enrichments of the active population of cells and greater
      than 90% purity after just one sorting round. In addition, we proved that we can
      sort the cellulase-expressing cells from mixtures containing less than 1% active
      cells. 

PMID- 25379083
TI  - Bacteria under the physical constraints of periodic micro-nanofluidic junctions
      reveal morphological plasticity and dynamic shifting of Min patterns.
AB  - Morphological plasticity is an important survival strategy for bacteria adapting
      to stressful environments in response to new physical constraints. Here, we
      demonstrate Escherichia coli morphological plasticity can be induced by switching
      stress levels through the physical constraints of periodic micro-nanofluidic
      junctions. Moreover, the generation of diverse morphological aberrancies requires
      the intact functions of the divisome- and elongasome-directed pathways. It is
      also intriguing that the altered morphologies are developed in bacteria
      undergoing morphological reversion as stresses are removed. Cell filamentation
      underlies the most dominant morphological phenotypes, in which transitions
      between the novel pattern formations by the spatial regulators of the divisome,
      i.e., the Min system, are observed, suggesting their potential linkage during
      morphological reversion. 

PMID- 25379084
TI  - Perspectives on surface nanobubbles.
AB  - Materials of nanoscale size exhibit properties that macroscopic materials often
      do not have. The same holds for bubbles on the nanoscale: nanoscale gaseous
      domains on a solid-liquid interface have surprising properties. These include the
      shape, the long life time, and even superstability. Such so-called surface
      nanobubbles may have wide applications. This prospective article covers the basic
      properties of surface nanobubbles and gives several examples of potential
      nanobubble applications in nanomaterials and nanodevices. For example,
      nanobubbles can be used as templates or nanostructures in surface
      functionalization. The nanobubbles produced in situ in a microfluidic system can
      even induce an autonomous motion of the nanoparticles on which they form. Their
      formation also has implications for the fluid transport in narrow channels in
      which they form. 

PMID- 25379086
TI  - Dynamics of red blood cells in microporous membranes.
AB  - We have performed microfluidic experiments with erythrocytes passing through a
      network of microchannels of 20-25 MUm width and 5 MUm of height. Red blood cells
      (RBCs) were flowing in countercurrent directions through microchannels connected
      by MUm pores. Thereby, we have observed interesting flow dynamics. All pores were
      blocked by erythrocytes. Some erythrocytes have passed through pores, depending
      on the channel size and cell elasticity. Many RBCs split into two or more smaller
      parts. Two types of splits were observed. In one type, the lipid bilayer and
      spectrin network were cut at the same time. In the second type, the lipid bilayer
      reconnected, but the part of spectrin network stayed outside the cell forming a
      rope like structure, which could eventually break. The microporous membrane
      results in multiple breakups of the cells, which can have various clinical
      implications, e.g., glomerulus hematuria and anemia of patients undergoing
      dialysis. The cell breakup procedure is similar to the one observed in the
      droplet breakage of viscoelastic liquids in confinement. 

PMID- 25379085
TI  - Microfluidic approaches to rapid and efficient aptamer selection.
AB  - With their advantages as molecular recognition elements, aptamers have been
      extensively studied and used for bioanalytical and biomedical applications.
      However, the process of enrichment and screening of aptamers remains a bottleneck
      for aptamer development. Recently, microfluidic methods have been increasingly
      used for rapid and efficient aptamer selection, showing their remarkable
      advantages over conventional methods. This review briefly introduces aptamers and
      their advantages. The conventional process of generating aptamers is discussed,
      followed by the analysis of the key obstacles to efficient aptamer selection.
      Microfluidic methods for highly efficient enrichment and screening of aptamers
      are reviewed in detail. 

PMID- 25379087
TI  - Micromixing visualization and quantification in a microscale multi-inlet vortex
      nanoprecipitation reactor using confocal-based reactive micro laser-induced
      fluorescence.
AB  - A technique for visualizing and quantifying reactive mixing for laminar and
      turbulent flow in a microscale chemical reactor using confocal-based microscopic
      laser induced fluorescence (confocal MU-LIF) was demonstrated in a microscale
      multi-inlet vortex nanoprecipitation reactor. Unlike passive scalar MU-LIF, the
      reactive MU-LIF technique is able to visualize and quantify micromixing effects.
      The confocal imaging results indicated that the flow in the reactor was laminar
      and steady for inlet Reynolds numbers of 10, 53, and 93. Mixing and reaction were
      incomplete at each of these Reynolds numbers. The results also suggested that
      although mixing by diffusion was enhanced near the midplane of the reactor at Rej
      = 53 and 93 due to very thin bands of acidic and basic fluid forming as the fluid
      spiraled towards the center of the reactor, near the top, and bottom walls of the
      reactor, the lower velocities due to fluid friction with the walls hindered the
      formation of these thin bands, and, thus, resulted in large regions of unmixed
      and unreacted fluid. At Rej = 240, the flow was turbulent and unsteady. The
      mixing and reaction processes were still found to be incomplete even at this
      highest Reynolds number. At the reactor midplane, the flow images at Rej = 240
      showed unmixed base fluid near the center of the reactor, suggesting that just as
      in the Rej = 53 and 93 cases, lower velocities near the top and bottom walls of
      the reactor hinder the mixing and rection of the acidic and basic streams.
      Ensemble averages of line-scan profiles for the Rej = 240 were then calculated to
      provide statistical quantification of the microscale mixing in the reactor. These
      results further demonstrate that even at this highest Reynolds number
      investigated, mixing and reaction are incomplete. Visualization and
      quantification of micromixing using this reactive MU-LIF technique can prove
      useful in the validation of computational fluid dynamics models of micromixing
      within microscale chemical reactors. 

PMID- 25379088
TI  - Fluctuations of DNA mobility in nanofluidic entropic traps.
AB  - We studied the mobility of DNA molecules driven by an electric field through a
      nanofluidic device containing a periodic array of deep and shallow regions termed
      entropic traps. The mobility of a group of DNA molecules was measured by
      fluorescent video microscopy. Since the depth of a shallow region is smaller than
      the DNA equilibrium size, DNA molecules are trapped for a characteristic time and
      must compress themselves to traverse the boundary between deep and shallow
      regions. Consistent with previous experimental results, we observed a nonlinear
      relationship between the mobility and electric field strength, and that longer
      DNA molecules have larger mobility. In repeated measurements under seemingly
      identical conditions, we measured fluctuations in the mobility significantly
      larger than expected from statistical variation. The variation was more
      pronounced for lower electric field strengths where the trapping time is
      considerable relative to the drift time. To determine the origin of these
      fluctuations, we investigated the dependence of the mobility on several
      variables: DNA concentration, ionic strength of the solvent, fluorescent dye
      staining ratio, electroosmotic flow, and electric field strength. The mobility
      fluctuations were moderately enhanced in conditions of reduced ionic strength and
      electroosmotic flow. 

PMID- 25379089
TI  - Microfluidic platform for the study of intercellular communication via soluble
      factor-cell and cell-cell paracrine signaling.
AB  - Diffusion of autocrine and paracrine signaling molecules allows cells to
      communicate in the absence of physical contact. This chemical-based, long-range
      communication serves crucial roles in tissue function, activation of the immune
      system, and other physiological functions. Despite its importance, few in vitro
      methods to study cell-cell signaling through paracrine factors are available
      today. Here, we report the design and validation of a microfluidic platform that
      enables (i) soluble molecule-cell and/or (ii) cell-cell paracrine signaling. In
      the microfluidic platform, multiple cell populations can be introduced into
      parallel channels. The channels are separated by arrays of posts allowing
      diffusion of paracrine molecules between cell populations. A computational
      analysis was performed to aid design of the microfluidic platform. Specifically,
      it revealed that channel spacing affects both spatial and temporal distribution
      of signaling molecules, while the initial concentration of the signaling molecule
      mainly affects the concentration of the signaling molecules excreted by the
      cells. To validate the microfluidic platform, a model system composed of the
      signaling molecule lipopolysaccharide, mouse macrophages, and engineered human
      embryonic kidney cells was introduced into the platform. Upon diffusion from the
      first channel to the second channel, lipopolysaccharide activates the macrophages
      which begin to produce TNF-alpha. The TNF-alpha diffuses from the second channel
      to the third channel to stimulate the kidney cells, which express green
      fluorescent protein (GFP) in response. By increasing the initial
      lipopolysaccharide concentration an increase in fluorescent response was
      recorded, demonstrating the ability to quantify intercellular communication
      between 3D cellular constructs using the microfluidic platform reported here.
      Overall, these studies provide a detailed analysis on how concentration of the
      initial signaling molecules, spatiotemporal dynamics, and inter-channel spacing
      affect intercellular communication. 

PMID- 25379090
TI  - Engineered three-dimensional microfluidic device for interrogating cell-cell
      interactions in the tumor microenvironment.
AB  - Stromal cells in the tumor microenvironment play a key role in the metastatic
      properties of a tumor. It is recognized that cancer-associated fibroblasts (CAFs)
      and endothelial cells secrete factors capable of influencing tumor cell migration
      into the blood or lymphatic vessels. We developed a microfluidic device that can
      be used to image the interactions between stromal cells and tumor cell spheroids
      in a three dimensional (3D) microenvironment while enabling external control of
      interstitial flow at an interface, which supports endothelial cells. The
      apparatus couples a 200-MUm channel with a semicircular well to mimic the
      interface of a blood vessel with the stroma, and the design allows for
      visualization of the interactions of interstitial flow, endothelial cells,
      leukocytes, and fibroblasts with the tumor cells. We observed that normal tissue
      associated fibroblasts (NAFs) contribute to the "single file" pattern of
      migration of tumor cells from the spheroid in the 3D microenvironment. In
      contrast, CAFs induce a rapid dispersion of tumor cells out of the spheroid with
      migration into the 3D matrix. Moreover, treatment of tumor spheroid cultures with
      the chemokine CXCL12 mimics the effect of the CAFs, resulting in similar patterns
      of dispersal of the tumor cells from the spheroid. Conversely, addition of CXCL12
      to co-cultures of NAFs with tumor spheroids did not mimic the effects observed
      with CAF co-cultures, suggesting that NAFs produce factors that stabilize the
      tumor spheroids to reduce their migration in response to CXCL12. 

PMID- 25379091
TI  - Modulating patterns of two-phase flow with electric fields.
AB  - This paper describes the use of electro-hydrodynamic actuation to control the
      transition between three major flow patterns of an aqueous-oil Newtonian flow in
      a microchannel: droplets, beads-on-a-string (BOAS), and multi-stream laminar
      flow. We observed interesting transitional flow patterns between droplets and
      BOAS as the electric field was modulated. The ability to control flow patterns of
      a two-phase fluid in a microchannel adds to the microfluidic tool box and
      improves our understanding of this interesting fluid behavior. 

PMID- 25379092
TI  - Characterization of microfluidic shear-dependent epithelial cell adhesion
      molecule immunocapture and enrichment of pancreatic cancer cells from blood cells
      with dielectrophoresis.
AB  - Current microfluidic techniques for isolating circulating tumor cells (CTCs) from
      cancer patient blood are limited by low capture purity, and dielectrophoresis
      (DEP) has the potential to complement existing immunocapture techniques to
      improve capture performance. We present a hybrid DEP and immunocapture Hele-Shaw
      flow cell to characterize DEP's effects on immunocapture of pancreatic cancer
      cells (Capan-1, PANC-1, and BxPC-3) and peripheral blood mononuclear cells
      (PBMCs) with an anti-EpCAM (epithelial cell adhesion molecule) antibody. By
      carefully specifying the applied electric field frequency, we demonstrate that
      pancreatic cancer cells are attracted to immunocapture surfaces by positive DEP
      whereas PBMCs are repelled by negative DEP. Using an exponential capture model to
      interpret our capture data, we show that immunocapture performance is dependent
      on the applied DEP force sign and magnitude, cell surface EpCAM expression level,
      and shear stress experienced by cells flowing in the capture device. Our work
      suggests that DEP can not only repel contaminating blood cells but also enhance
      capture of cancer cell populations that are less likely to be captured by
      traditional immunocapture methods. This combination of DEP and immunocapture
      techniques to potentially increase CTC capture purity can facilitate subsequent
      biological analyses of captured CTCs and research on cancer metastasis and drug
      therapies. 

PMID- 25379094
TI  - A chitosan coated monolith for nucleic acid capture in a thermoplastic
      microfluidic chip.
AB  - A technique for microfluidic, pH modulated DNA capture and purification using
      chitosan functionalized glycidyl methacrylate monoliths is presented. Highly
      porous polymer monoliths are formed and subsequently functionalized off-chip in a
      batch process before insertion into thermoplastic microchannels prior to solvent
      bonding, simplifying the overall fabrication process by eliminating the need for
      on-chip surface modifications. The monolith anchoring method allows for the use
      of large cross-section monoliths enabling high flowrates and high DNA capture
      capacity with a minimum of added design complexity. Using monolith capture
      elements requiring less than 1 mm(2) of chip surface area, loading levels above
      100 ng are demonstrated, with DNA capture and elution efficiency of 54.2% +/-
      14.2% achieved. 

PMID- 25379093
TI  - A micropillar array for sample concentration via in-plane evaporation.
AB  - We present a method to perform sample concentration within a lab-on-a-chip using
      a microfluidic structure which controls the liquid-gas interface through a
      micropillar array fabricated in polydimethylsiloxane between microfluidic
      channels. The microstructure confines the liquid flow and a thermal gradient is
      used to drive evaporation at the liquid-gas-interface. The evaporation occurs in
      plane to the microfluidic device, allowing for precise control of the ambient
      environment. This method is demonstrated with a sample containing 1 MUm, 100 nm
      fluorescent beads and SYTO-9 labelled Escherichia coli bacteria. Over 100 s, the
      fluorescent beads and bacteria are concentrated by a factor of 10. 

PMID- 25379095
TI  - Microfluidic culture platform for studying neuronal response to mild to very mild
      axonal stretch injury.
AB  - A new model for studying localised axonal stretch injury is presented, using a
      microfluidic device to selectively culture axons on a thin, flexible poly
      (dimethylsiloxane) membrane which can be deflected upward to stretch the axons. A
      very mild (0.5% strain) or mild stretch injury (5% strain) was applied to primary
      cortical neurons after 7 days growth in vitro. The extent of distal degeneration
      was quantified using the degenerative index (DI, the ratio of fragmented axon
      area to total axon area) of axons fixed at 24 h and 72 h post injury (PI), and
      immunolabelled for the axon specific, microtubule associated protein-tau. At 24 h
      PI following very mild injuries (0.5%), the majority of the axons remained intact
      and healthy with no significant difference in DI when compared to the control,
      but at 72 h PI, the DI increased significantly (DI = 0.11 +/- 0.03). Remarkably,
      dendritic beading in the somal compartment was observed at 24 h PI, indicative of
      dying back degeneration. When the injury level was increased (5% stretch, mild
      injury), microtubule fragmentation along the injured axons was observed, with a
      significant increase in DI at 24 h PI (DI = 0.17 +/- 0.02) and 72 h PI (DI = 0.18
      +/- 0.01), relative to uninjured axons. The responses observed for both mild and
      very mild injuries are similar to those observed in the in vivo models of
      traumatic brain injury, suggesting that this model can be used to study neuronal
      trauma and will provide new insights into the cellular and molecular alterations
      characterizing the neuronal response to discrete axonal injury. 

PMID- 25379096
TI  - Electrocoalescence based serial dilution of microfluidic droplets.
AB  - Dilution of microfluidic droplets where the concentration of a reagent is
      incrementally varied is a key operation in drop-based biological analysis. Here,
      we present an electrocoalescence based dilution scheme for droplets based on
      merging between moving and parked drops. We study the effects of fluidic and
      electrical parameters on the dilution process. Highly consistent coalescence and
      fine resolution in dilution factor are achieved with an AC signal as low as 10 V
      even though the electrodes are separated from the fluidic channel by insulator.
      We find that the amount of material exchange between the droplets per coalescence
      event is high for low capillary number. We also observe different types of
      coalescence depending on the flow and electrical parameters and discuss their
      influence on the rate of dilution. Overall, we find the key parameter governing
      the rate of dilution is the duration of coalescence between the moving and parked
      drop. The proposed design is simple incorporating the channel electrodes in the
      same layer as that of the fluidic channels. Our approach allows on-demand and
      controlled dilution of droplets and is simple enough to be useful for assays that
      require serial dilutions. The approach can also be useful for applications where
      there is a need to replace or wash fluid from stored drops. 

PMID- 25379097
TI  - Modulation of rotation-induced lift force for cell filtration in a low aspect
      ratio microchannel.
AB  - Cell filtration is a critical step in sample preparation in many bioapplications.
      Herein, we report on a simple, filter-free, microfluidic platform based on
      hydrodynamic inertial migration. Our approach builds on the concept of two-stage
      inertial migration which permits precise prediction of microparticle position
      within the microchannel. Our design manipulates equilibrium positions of larger
      microparticles by modulating rotation-induced lift force in a low aspect ratio
      microchannel. Here, we demonstrate filtration of microparticles with extreme
      efficiency (>99%). Using multiple prostate cell lines (LNCaP and human prostate
      epithelial tumor cells), we show filtration from spiked blood, with 3-fold
      concentration and >83% viability. Results of a proliferation assay show normal
      cell division and suggest no negative effects on intrinsic properties.
      Considering the planar low-aspect-ratio structure and predictable focusing, we
      envision promising applications and easy integration with existing lab-on-a-chip
      systems. 

PMID- 25379098
TI  - Droplet-based microfluidic washing module for magnetic particle-based assays.
AB  - In this paper, we propose a continuous flow droplet-based microfluidic platform
      for magnetic particle-based assays by employing in-droplet washing. The droplet
      based washing was implemented by traversing functionalized magnetic particles
      across a laterally merged droplet from one side (containing sample and reagent)
      to the other (containing buffer) by an external magnetic field. Consequently, the
      magnetic particles were extracted to a parallel-synchronized train of washing
      buffer droplets, and unbound reagents were left in an original train of sample
      droplets. To realize the droplet-based washing function, the following four
      procedures were sequentially carried in a droplet-based microfluidic device:
      parallel synchronization of two trains of droplets by using a ladder-like channel
      network; lateral electrocoalescence by an electric field; magnetic particle
      manipulation by a magnetic field; and asymmetrical splitting of merged droplets.
      For the stable droplet synchronization and electrocoalescence, we optimized
      droplet generation conditions by varying the flow rate ratio (or droplet size).
      Image analysis was carried out to determine the fluorescent intensity of reagents
      before and after the washing step. As a result, the unbound reagents in sample
      droplets were significantly removed by more than a factor of 25 in the single
      washing step, while the magnetic particles were successfully extracted into
      washing buffer droplets. As a proof-of-principle, we demonstrate a magnetic
      particle-based immunoassay with streptavidin-coated magnetic particles and
      fluorescently labelled biotin in the proposed continuous flow droplet-based
      microfluidic platform. 

PMID- 25379099
TI  - Microfluidic-based measurement of erythrocyte sedimentation rate for biophysical
      assessment of blood in an in vivo malaria-infected mouse.
AB  - This study suggests a new erythrocyte sedimentation rate (ESR) measurement method
      for the biophysical assessment of blood by using a microfluidic device. For an
      effective ESR measurement, a disposable syringe filled with blood is turned
      upside down and aligned at 180 degrees  with respect to gravitational direction.
      When the blood sample is delivered into the microfluidic device from the top
      position of the syringe, the hematocrit of blood flowing in the microfluidic
      channel decreases because the red blood cell-depleted region is increased from
      the top region of the syringe. The variation of hematocrit is evaluated by
      consecutively capturing images and conducting digital image processing technique
      for 10 min. The dynamic variation of ESR is quantitatively evaluated using two
      representative parameters, namely, time constant (lambda) and ESR-area (AESR). To
      check the performance of the proposed method, blood samples with various ESR
      values are prepared by adding different concentrations of dextran solution.
      lambda and AESR are quantitatively evaluated by using the proposed method and a
      conventional method, respectively. The proposed method can be used to measure ESR
      with superior reliability, compared with the conventional method. The proposed
      method can also be used to quantify ESR of blood collected from malaria-infected
      mouse under in vivo condition. To indirectly compare with the results obtained by
      the proposed method, the viscosity and velocity of the blood are measured using
      the microfluidic device. As a result, the biophysical properties, including ESR
      and viscosity of blood, are significantly influenced by the parasitemia level.
      These experimental demonstrations support the notion that the proposed method is
      capable of effectively monitoring the biophysical properties of blood. 

PMID- 25379100
TI  - Dielectrophoretic sample preparation for environmental monitoring of
      microorganisms: Soil particle removal.
AB  - Detection of pathogens from environmental samples is often hampered by sensors
      interacting with environmental particles such as soot, pollen, or environmental
      dust such as soil or clay. These particles may be of similar size to the target
      bacterium, preventing removal by filtration, but may non-specifically bind to
      sensor surfaces, fouling them and causing artefactual results. In this paper, we
      report the selective manipulation of soil particles using an AC electrokinetic
      microfluidic system. Four heterogeneous soil samples (smectic clay, kaolinitic
      clay, peaty loam, and sandy loam) were characterised using dielectrophoresis to
      identify the electrical difference to a target organism. A flow-cell device was
      then constructed to evaluate dielectrophoretic separation of bacteria and clay in
      a continous flow through mode. The average separation efficiency of the system
      across all soil types was found to be 68.7% with a maximal separation efficiency
      for kaolinitic clay at 87.6%. This represents the first attempt to separate soil
      particles from bacteria using dielectrophoresis and indicate that the technique
      shows significant promise; with appropriate system optimisation, we believe that
      this preliminary study represents an opportunity to develop a simple yet highly
      effective sample processing system. 

PMID- 25379101
TI  - A novel miniature dynamic microfluidic cell culture platform using electro
      osmosis diode pumping.
AB  - An electro-osmosis (EOS) diode pumping platform capable of culturing cells in
      fluidic cellular micro-environments particularly at low volume flow rates has
      been developed. Diode pumps have been shown to be a viable alternative to
      mechanically driven pumps. Typically electrokinetic micro-pumps were limited to
      low-concentration solutions (<=10 mM). In our approach, surface mount diodes were
      embedded along the sidewalls of a microchannel to rectify externally applied
      alternating current into pulsed direct current power across the diodes in order
      to generate EOS flows. This approach has for the first time generated flows at
      ultra-low flow rates (from 2.0 nl/s to 12.3 nl/s) in aqueous solutions with
      concentrations greater than 100 mM. The range of flow was generated by changing
      the electric field strength applied to the diodes from 0.5 Vpp/cm to 10 Vpp/cm.
      Embedding an additional diode on the upper surface of the enclosed microchannel
      increased flow rates further. We characterized the diode pump-driven fluidics in
      terms of intensities and frequencies of electric inputs, pH values of solutions,
      and solution types. As part of this study, we found that the growth of A549 human
      lung cancer cells was positively affected in the microfluidic diode pumping
      system. Though the chemical reaction compromised the fluidic control overtime,
      the system could be maintained fully functional over a long time if the solution
      was changed every hour. In conclusion, the advantage of miniature size and
      ability to accurately control fluids at ultra-low volume flow rates can make this
      diode pumping system attractive to lab-on-a-chip applications and biomedical
      engineering in vitro studies. 

PMID- 25379103
TI  - Magnetophoretic-based microfluidic device for DNA isolation.
AB  - This paper presents a continuous flow microfluidic device for the separation of
      DNA from blood using magnetophoresis for biological applications and analysis.
      This microfluidic bio-separation device has several benefits, including decreased
      sample handling, smaller sample and reagent volumes, faster isolation time, and
      decreased cost to perform DNA isolation. One of the key features of this device
      is the use of short-range magnetic field gradients, generated by a micro
      patterned nickel array on the bottom surface of the separation channel. In
      addition, the device utilizes an array of oppositely oriented, external permanent
      magnets to produce strong long-range field gradients at the interfaces between
      magnets, further increasing the effectiveness of the device. A comprehensive
      simulation is performed using COMSOL Multiphysics to study the effect of various
      parameters on the magnetic flux within the separation channel. Additionally, a
      microfluidic device is designed, fabricated, and tested to isolate DNA from
      blood. The results show that the device has the capability of separating DNA from
      a blood sample with a purity of 1.8 or higher, a yield of up to 33 MUg of
      polymerase chain reaction ready DNA per milliliter of blood, and a volumetric
      throughput of up to 50 ml/h. 

PMID- 25379102
TI  - Examination of the role of transient receptor potential vanilloid type 4 in
      endothelial responses to shear forces.
AB  - Shear stress is the major mechanical force applied on vascular endothelial cells
      by blood flow, and is a crucial factor in normal vascular physiology and in the
      development of some vascular pathologies. The exact mechanisms of cellular
      mechano-transduction in mammalian cells and tissues have not yet been elucidated,
      but it is known that mechanically sensitive receptors and ion channels play a
      crucial role. This paper describes the use of a novel and efficient microfluidic
      device to study mechanically-sensitive receptors and ion channels in vitro, which
      has three independent channels from which recordings can be made and has a small
      surface area such that fewer cells are required than for conventional flow
      chambers. The contoured channels of the device enabled examination of a range of
      shear stresses in one field of view, which is not possible with parallel plate
      flow chambers and other previously used devices, where one level of flow-induced
      shear stress is produced per fixed flow-rate. We exposed bovine aortic
      endothelial cells to different levels of shear stress, and measured the resulting
      change in intracellular calcium levels ([Ca(2+)]i) using the fluorescent calcium
      sensitive dye Fluo-4AM. Shear stress caused an elevation of [Ca(2+)]i that was
      proportional to the level of shear experienced. The response was temperature
      dependant such that at lower temperatures more shear stress was required to
      elicit a given level of calcium signal and the magnitude of influx was reduced.
      We demonstrated that shear stress-induced elevations in [Ca(2+)]i are largely due
      to calcium influx through the transient receptor potential vanilloid type 4 ion
      channel. 

PMID- 25379104
TI  - Refillable and magnetically actuated drug delivery system using pear-shaped
      viscoelastic membrane.
AB  - We report a refillable and valveless drug delivery device actuated by an external
      magnetic field for on-demand drug release to treat localized diseases. The device
      features a pear-shaped viscoelastic magnetic membrane inducing asymmetrical
      deflection and consecutive touchdown motion to the bottom of the dome-shaped drug
      reservoir in response to a magnetic field, thus achieving controlled discharge of
      the drug. Maximum drug release with 18 +/- 1.5 MUg per actuation was achieved
      under a 500 mT magnetic flux density, and various controlled drug doses were
      investigated with the combination of the number of accumulated actuations and the
      strength of the magnetic field. 

PMID- 25379105
TI  - Tunable electrochemical pH modulation in a microchannel monitored via the proton
      coupled electro-oxidation of hydroquinone.
AB  - Electrochemistry is a promising tool for microfluidic systems because it is
      relatively inexpensive, structures are simple to fabricate, and it is straight
      forward to interface electronically. While most widely used in microfluidics for
      chemical detection or as the transduction mechanism for molecular probes,
      electrochemical methods can also be used to efficiently alter the chemical
      composition of small (typically <100 nl) microfluidic volumes in a manner that
      improves or enables subsequent measurements and sample processing steps. Here,
      solvent (H2O) electrolysis is performed quantitatively at a microchannel Pt band
      electrode to increase microchannel pH. The change in microchannel pH is
      simultaneously tracked at a downstream electrode by monitoring changes in the i-V
      characteristics of the proton-coupled electro-oxidation of hydroquinone, thus
      providing real-time measurement of the protonated forms of hydroquinone from
      which the pH can be determined in a straightforward manner. Relative peak heights
      for protonated and deprotonated hydroquinone forms are in good agreement with
      expected pH changes by measured electrolysis rates, demonstrating that solvent
      electrolysis can be used to provide tunable, quantitative pH control within a
      microchannel. 

PMID- 25379106
TI  - Simplified prototyping of perfusable polystyrene microfluidics.
AB  - Cell culture in microfluidic systems has primarily been conducted in devices
      comprised of polydimethylsiloxane (PDMS) or other elastomers. As polystyrene (PS)
      is the most characterized and commonly used substrate material for cell culture,
      microfluidic cell culture would ideally be conducted in PS-based microsystems
      that also enable tight control of perfusion and hydrodynamic conditions, which
      are especially important for culture of vascular cell types. Here, we report a
      simple method to prototype perfusable PS microfluidics for endothelial cell
      culture under flow that can be fabricated using standard lithography and wet
      laboratory equipment to enable stable perfusion at shear stresses up to 300
      dyn/cm(2) and pumping pressures up to 26 kPa for at least 100 h. This technique
      can also be extended to fabricate perfusable hybrid PS-PDMS microfluidics of
      which one application is for increased efficiency of viral transduction in non
      adherent suspension cells by leveraging the high surface area to volume ratio of
      microfluidics and adhesion molecules that are optimized for PS substrates. These
      biologically compatible microfluidic devices can be made more accessible to
      biological-based laboratories through the outsourcing of lithography to various
      available microfluidic foundries. 

PMID- 25379107
TI  - Microstructured multi-well plate for three-dimensional packed cell seeding and
      hepatocyte cell culture.
AB  - In this article, we present a microstructured multi-well plate for enabling three
      dimensional (3D) high density seeding and culture of cells through the use of a
      standard laboratory centrifuge to promote and maintain 3D tissue-like cellular
      morphology and cell-specific functionality in vitro without the addition of
      animal derived or synthetic matrices or coagulants. Each well has microfeatures
      on the bottom that are comprised of a series of ditches/open microchannels. The
      dimensions of the microchannels promote and maintain 3D tissue-like cellular
      morphology and cell-specific functionality in vitro. After cell seeding with a
      standard pipette, the microstructured multi-well plates were centrifuged to
      tightly pack cells inside the ditches in order to enhance cell-cell interactions
      and induce formation of 3D cellular structures during cell culture. Cell-cell
      interactions were optimized based on cell packing by considering dimensions of
      the ditches/open microchannels, orientation of the microstructured multi-well
      plate during centrifugation, cell seeding density, and the centrifugal force and
      time. With the optimized cell packing conditions, we demonstrated that after 7
      days of cell culture, primary human hepatocytes adhered tightly together to form
      cord-like structures that resembled 3D tissue-like cellular architecture.
      Importantly, cell membrane polarity was restored without the addition of animal
      derived or synthetic matrices or coagulants. 

PMID- 25379108
TI  - Optimizing design and fabrication of microfluidic devices for cell cultures: An
      effective approach to control cell microenvironment in three dimensions.
AB  - The effects of gradients of bioactive molecules on the cell microenvironment are
      crucial in several biological processes, such as chemotaxis, angiogenesis, and
      tumor progression. The elucidation of the basic mechanisms regulating cell
      responses to gradients requires a tight control of the spatio-temporal features
      of such gradients. Microfluidics integrating 3D gels are useful tools to fulfill
      this requirement. However, even tiny flaws in the design or in the fabrication
      process may severely impair microenvironmental control, thus leading to
      inconsistent results. Here, we report a sequence of actions aimed at the design
      and fabrication of a reliable and robust microfluidic device integrated with
      collagen gel for cell culturing in 3D, subjected to a predetermined gradient of
      biomolecular signals. In particular, we developed a simple and effective solution
      to the frequently occurring technical problems of gas bubble formation and 3D
      matrix collapsing or detaching from the walls. The device here proposed, in
      Polydimethylsiloxane, was designed to improve the stability of the cell-laden
      hydrogel, where bubble deprived conditioning media flow laterally to the gel. We
      report the correct procedure to fill the device with the cell populated gel
      avoiding the entrapment of gas bubbles, yet maintaining cell viability. Numerical
      simulations and experiments with fluorescent probes demonstrated the
      establishment and stability of a concentration gradient across the gel. Finally,
      chemotaxis experiments of human Mesenchymal Stem Cells under the effects of Bone
      Morphogenetic Protein-2 gradients were performed in order to demonstrate the
      efficacy of the system in controlling cell microenvironment. The proposed
      procedure is sufficiently versatile and simple to be used also for different
      device geometries or experimental setups. 

PMID- 25379110
TI  - A polystyrene-based microfluidic device with three-dimensional interconnected
      microporous walls for perfusion cell culture.
AB  - In this article, we present a simple, rapid prototyped polystyrene-based
      microfluidic device with three-dimensional (3D) interconnected microporous walls
      for long term perfusion cell culture. Patterned 3D interconnected microporous
      structures were created by a chemical treatment together with a protective mask
      and the native hydrophobic nature of the microporous structures were selectively
      made hydrophilic using oxygen plasma treatment together with a protective mask.
      Using this polystyrene-based cell culture microfluidic device, we successfully
      demonstrated the support of four days perfusion cell culture of hepatocytes (C3A
      cells). 

PMID- 25379109
TI  - Vascular smooth muscle cell culture in microfluidic devices.
AB  - This paper presents a microfluidic device enabling culture of vascular smooth
      muscle cells (VSMCs) where extracellular matrix coating, VSMC seeding, culture,
      and immunostaining are demonstrated in a tubing-free manner. By optimizing
      droplet volume differences between inlets and outlets of micro channels, VSMCs
      were evenly seeded into microfluidic devices. Furthermore, the effects of
      extracellular matrix (e.g., collagen, poly-l-Lysine (PLL), and fibronectin) on
      VSMC proliferation and phenotype expression were explored. As a platform
      technology, this microfluidic device may function as a new VSMC culture model
      enabling VSMC studies. 

PMID- 25379111
TI  - [Epidemiological, clinical and therapeutic aspects of otitis externa: about 801
      cases].

PMID- 25379112
TI  - [Beware of cosmetic lenses].

PMID- 25379113
TI  - [Cutaneous mesenchymal tumors: about 121 cases].

PMID- 25379114
TI  - Traumatic peroneal nerve injury in an adolescent with asymptomatic tibial
      osteochondroma.

PMID- 25379115
TI  - A study of the prevalence of diarrhoeagenic Escherichia coli in children from
      Gwagwalada, Federal Capital Territory, Nigeria.
AB  - INTRODUCTION: Diarrhoeagenic Escherichia coli (DEC) are major causes of diarrhoea
      in Nigeria. This study was conducted to determine the prevalence of diarrhoea
      caused by DEC within the Federal Capital Territory, Abuja, Nigeria. METHODS: A
      total of 730 rectal swabs obtained from 201 children with diarrhoea and 529
      healthy controls aged 0-24 months were cultured for the isolation of Escherichia
      coli. All E. coli isolates were investigated by PCR to determine their pathotype.
      RESULTS: A total of 61 DEC strains were recovered at a rate of 18.4% and 2.6%
      from children with diarrhoea and healthy controls respectively. The DEC strains
      recovered were Enteroaggregative Escherichia coli (34.4%), Shiga-toxin producing
      Escherichia coli (31.1%), Enterotoxigenic Escherichia coli(18.0%), typical
      enteropathogenic Escherichia coli (15.0%) and Enteroinvasive Escherichia coli
      (1.6%). Shiga-toxin producing Escherichia coli andEnteroinvasive Escherichia coli
      were recovered only from children suffering from diarrhoea and the overall
      prevalence of DEC strains was significantly higher among the children with
      diarrhoea (P < 0.0001). The number of DEC strains obtained during the dry season
      was significantly higher (P = 0.012) than the number obtained in the rainy
      season. CONCLUSION: Diarrhoea caused by E. coli in the Nigerian children studied
      is associated with several diarrhoeagenic pathotypes and a significant proportion
      of the healthy children were found to harbour EAEC and ETEC strains. These
      asymptomatic carriers may be regarded as potential transmitters of infection to
      vulnerable children in the study area.

PMID- 25379116
TI  - [When an erythema can save a life].

PMID- 25379117
TI  - [Cerebral hydatid cyst in children: report of 5 cases].

PMID- 25379118
TI  - [Complete radiological response of meningeal hemangiopericytoma after adjuvant
      radiotherapy to incomplete excision].

PMID- 25379120
TI  - The Hispanic Americans Baseline Alcohol Survey (HABLAS):Predictive invariance of
      Demographic Characteristics on Attitudes towards Alcohol across Hispanic National
      Groups.
AB  - This study compares the demographic predictors of items assessing attitudes
      towards drinking across Hispanic national groups. Data were from the 2006
      Hispanic Americans Baseline Alcohol Survey (HABLAS), which used a multistage
      cluster sample design to interview 5,224 individuals randomly selected from the
      household population in Miami, New York, Philadelphia, Houston, and Los Angeles.
      Predictive invariance of demographic predictors of alcohol attitudes over four
      Hispanic national groups (Puerto Rican, Cuban, Mexican, and South/Central
      Americans) was examined using multiple-group seemingly unrelated probit
      regression. The analyses examined whether the influence of various demographic
      predictors varied across the Hispanic national groups in their regression
      coefficients, item intercepts, and error correlations. The hypothesis of
      predictive invariance was supported. Hispanic groups did not differ in how
      demographic predictors related to individual attitudinal items (regression slopes
      were invariant). In addition, the groups did not differ in attitudinal
      endorsement rates once demographic covariates were taken into account (item
      intercepts were invariant). Although Hispanic groups have different attitudes
      about alcohol, the influence of multiple demographic characteristics on alcohol
      attitudes operates similarly across Hispanic groups. Future models of drinking
      behavior in adult Hispanics need not posit moderating effects of group on the
      relation between these background characteristics and attitudes.

PMID- 25379121
TI  - The search for a neural basis of communication: Learning, memory, perception and
      performance of vocal signals.
AB  - Brain mechanisms for communication must establish a correspondence between
      sensory perception and motor performance of individual signals. A class of
      neurons in the swamp sparrow forebrain is well suited for that task. Recordings
      from awake and freely behaving birds reveal that those cells express categorical
      auditory responses to changes in note duration, a learned feature of their songs,
      and the neural response boundary accurately predicts the perceptual boundary
      measured in field studies. Extremely precise auditory activity of those cells
      represents not only songs in the adult repertoire but also songs of others and
      tutor songs, including those imitated only very few times or perhaps not at all
      during development. Furthermore, recordings during singing reveal that these
      cells also express a temporally precise auditory-vocal correspondence, and limits
      on auditory responses to extremely challenging tutor songs may contribute to the
      emergence of a novel form of song syntax. Therefore, these forebrain neurons
      provide a mechanism through which sensory perception may influence motor
      performance to enable imitation. These cells constitute the projection from a
      premotor cortical-like area into the avian striatum (HVCX neurons), and data from
      humans implicate analogous or homologous areas in perception and performance of
      the sounds used in speech.

PMID- 25379122
TI  - PELVIC FLOOR SYMPTOMS AND QUALITY OF LIFE ANALYSES IN WOMEN UNDERGOING SURGERY
      FOR RECTAL PROLPASE.
AB  - OBJECTIVE: Characterize pelvic floor symptom distress and impact, sexual function
      and quality of life in women who underwent rectal prolapse surgery. METHODS:
      Subjects undergoing rectal prolapse surgery from 2004-2009 completed
      questionnaires including the Pelvic Floor Distress Inventory, Pelvic Floor Impact
      Questionnaire, and the Prolapse/Urinary Incontinence Sexual Questionnaire.
      Baseline demographic, medical, and surgical characteristics were extracted by
      chart review. Demographic and clinic outcomes of women undergoing transperineal
      and abdominal approaches were compared. Wilcoxon rank-sum test was used for
      continuous variables and Fisher's exact test for categorical measures. RESULTS:
      45 were identified; two deceased at follow-up. 28/43 subjects (65.1%) responded
      to the questionnaires. Mean time from original procedure was 3.9 +/- 3.1 years.
      No differences in median total Pelvic Floor Distress Inventory, Pelvic Floor
      Impact Questionnaire, and subscale scores, and Prolapse/Urinary Incontinence
      Sexual Questionnaire scores in women undergoing open rectopexy versus
      transperineal proctectomy were seen (all p>0.05). 26 (60%) participants answered
      the Prolapse/Urinary Incontinence Sexual Questionnaire, nine reported sexual
      activity within the last month. All underwent abdominal procedures. CONCLUSION:
      There are few colorectal or other pelvic floor symptoms after rectal prolapse
      repair. Robust prospective studies are needed to more fully characterize and
      understand issues associated with rectal prolapse surgery in women.

PMID- 25379123
TI  - Trauma Narratives: It's What You Say, Not How You Say It.
AB  - Structural and content- related features of trauma narratives of traumatic events
      may help explain the development of PTSD. In a sample of 35 female assault
      survivors, we examined the association between the structure and content of
      trauma narratives and PTSD and other trauma-related reactions (i.e., depression,
      anxiety, anger, dissociation, and guilt). When controlling for recounting style
      and recounting distress, narrative structure was not strongly associated with
      PTSD or other trauma-related reactions. In contrast, the content of the trauma
      narratives (more positive and negative emotion words, higher cognitive process,
      and less self-focus being) was associated with lower symptomatology. Taken
      together, trauma narrative content rather than grammatical structure of the
      narrative may be more reflective of underlying emotional processing of the
      traumatic memory or lack thereof.

PMID- 25379124
TI  - Management of the temporomandibular joint after ablative surgery.
AB  - Management of the temporomandibular joint in ablative head and neck surgery is
      controversial with no standardized approach. The aim of the study was to
      establish risk-based guidelines for the management of the temporomandibular joint
      after ablative surgery. Analysis of all patients' records receiving ablative
      surgery involving the temporomandibular joint in the Department of Cranio
      Maxillofacial and Oral Surgery, University Hospital of Zurich, from 2001 to 2012,
      was performed, identifying 15 patients and 14 reconstructive procedures. A
      literature search was done identifying all relevant literature on current
      approaches. Applicable cohorts were constructed, and relevant risks were
      extrapolated. Evaluated studies are not uniform in their reporting with
      nonhomogeneous patient groups. A diverse approach is used in the management of
      these patients with complications such as infection, ankylosis, limited mouth
      opening, plate penetration in the skull base, and plate loosening. Risk factors
      for complications appear to be radiation, costochondral graft, disk loss, and
      plate use alone. Clinical data suggest use of a plate with metal condyle
      reconstructions and previous radiation therapy as potential risks factors.
      Employing literature evidence and cumulated clinical data, a risk-based flowchart
      was developed to assist surgical decision making. Risk factors such as radiation,
      disk preservation, and soft tissue conditions are important complication
      associated factors when planning surgery. Free vascularized fibula grafts appear
      to have the least complications that must be weighed against donor site
      morbidity. 

PMID- 25379125
TI  - Supporting the diffusion of healthy public policy in Canada: the Prevention
      Policies Directory.
AB  - Healthy public policy plays an essential role in a comprehensive public health
      approach to preventing cancer and chronic disease. Public policies spread through
      the 'policy diffusion' process, enabling governments to learn from another's
      enacted policy solutions. The Prevention Policies Directory (the Directory), an
      online database of municipal, provincial/territorial, and federal cancer and
      chronic disease prevention policies from across Canada, was developed to
      facilitate the diffusion of healthy public policies and support the work of
      prevention researchers, practitioners, and policy specialists. This information
      technology solution was implemented, through a participatory engagement approach,
      as a communication channel or policy knowledge transfer tool. It also addressed
      the intrinsic shortcomings of environmental scanning for policy surveillance and
      monitoring. A combination of quantitative web metrics and qualitative anecdotal
      evidence have illustrated that the Directory is becoming an important tool for
      healthy public policy surveillance and policy diffusion in Canada. 

PMID- 25379126
TI  - Emergency Medical Text Classifier: New system improves processing and
      classification of triage notes.
AB  - OBJECTIVE: Automated syndrome classification aims to aid near real-time syndromic
      surveillance to serve as an early warning system for disease outbreaks, using
      Emergency Department (ED) data. We present a system that improves the automatic
      classification of an ED record with triage note into one or more syndrome
      categories using the vector space model coupled with a 'learning' module that
      employs a pseudo-relevance feedback mechanism. MATERIALS AND METHODS: Terms from
      standard syndrome definitions are used to construct an initial reference
      dictionary for generating the syndrome and triage note vectors. Based on cosine
      similarity between the vectors, each record is classified into a syndrome
      category. We then take terms from the top-ranked records that belong to the
      syndrome of interest as feedback. These terms are added to the reference
      dictionary and the process is repeated to determine the final classification. The
      system was tested on two different datasets for each of three syndromes: Gastro
      Intestinal (GI), Respiratory (Resp) and Fever-Rash (FR). Performance was measured
      in terms of sensitivity (Se) and specificity (Sp). RESULTS: The use of relevance
      feedback produced high values of sensitivity and specificity for all three
      syndromes in both test sets: GI: 90% and 71%, Resp: 97% and 73%, FR: 100% and
      87%, respectively, in test set 1, and GI: 88% and 69%, Resp: 87% and 61%, FR: 97%
      and 71%, respectively, in test set 2. CONCLUSIONS: The new system for pre
      processing and syndromic classification of ED records with triage notes achieved
      improvements in Se and Sp. Our results also demonstrate that the system can be
      tuned to achieve different levels of performance based on user requirements.

PMID- 25379127
TI  - Calls to the British Columbia Drug and Poison Information Centre: A summary of
      differences by health service areas.
AB  - OBJECTIVES: Poison control centres provide information on the management of
      poisoning incidents. The British Columbia (BC) Drug and Poison Information Centre
      recently implemented an electronic database system for recording case
      information, making it easier to use case data as a potential source of
      population-based information on health services usage and health status. This
      descriptive analysis maps poisoning case rates in BC, highlighting differences in
      patient age, substance type, medical outcome, and caller location. METHODS: There
      were 50,621 human exposure cases recorded during 2012 and 2013. Postal code or
      city name was used to assign each case to a Health Service Delivery Area (HSDA).
      Case rates per 1,000 person-years were calculated, including crude rates, age
      standardized rates, age-specific rates, and rates by substance type, medical
      outcome, and caller location. RESULTS: The lowest case rate was observed in
      Richmond, a city where many residents do not speak English as a first language.
      The highest rate was observed in the Northwest region, where the economy is
      driven by resource extraction. Pharmaceutical exposures were elevated in the
      sparsely populated northern and eastern areas. Calls from health care facilities
      were highest in the Northwest region, where there are many remote Aboriginal
      communities. CONCLUSIONS: Case rates were generally highest in the primarily
      rural northern and eastern areas of the province. Considering these results
      alongside contextual factors informs further investigation and action: addressing
      cultural and language barriers to accessing poison centre services, and
      developing a public health surveillance system for severe poisoning events in
      rural and remote communities.

PMID- 25379119
TI  - ICON: chronic rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is a public health problem that has a significant
      socio-economic impact. Moreover, the complexity of this disease due to its
      heterogeneous nature based on the underlying pathophysiology - leading to
      different disease variants - further complicates our understanding and directions
      for the most appropriate targeted treatment strategies. Several
      International/national guidelines/position papers and/or consensus documents are
      available that present the current knowledge and treatment strategies for CRS.
      Yet there are many challenges to the management of CRS especially in the case of
      the more severe and refractory forms of disease. Therefore, the International
      Collaboration in Asthma, Allergy and Immunology (iCAALL), a collaboration between
      EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus
      (ICON) on Chronic Rhinosinusitis. The purpose of this ICON on CRS is to highlight
      the key common messages from the existing guidelines, the differences in
      recommendations as well as the gaps in our current knowledge of CRS, thus
      providing a concise reference. In this document we discuss the definition of the
      disease, its relevance, pharmacoeconomics, pathophysiology, phenotypes and
      endotypes, genetics and risk factors, natural history and co-morbidities as well
      as clinical manifestations and treatment options in both adults and children
      comprising pharmacotherapy, surgical interventions and more recent biological
      approaches. Finally, we have also highlighted the unmet needs that wait to be
      addressed through future research. 

PMID- 25379128
TI  - Development and implementation of a clinical and business intelligence system for
      the Florida health data warehouse.
AB  - OBJECTIVE: To develop and implement a Clinical and Business Intelligence (CBI)
      system for the Florida Health Data Warehouse (FHDW) in order to bridge the gap
      between Florida's healthcare stakeholders and the health data archived in FHWD.
      MATERIALS AND METHODS: A gap analysis study has been conducted to evaluate the
      technological divide between the relevant users and FHWD health data, which is
      maintained by the Broward Regional Health Planning Council (BRHPC). The study
      revealed a gap between the health care data and the decision makers that utilize
      the FHDW data. To bridge the gap, a CBI system was proposed, developed and
      implemented by BRHPC as a viable solution to address this issue, using the System
      Development Life Cycle methodology. RESULTS: The CBI system was successfully
      implemented and yielded a number of positive outcomes. In addition to
      significantly shortening the time required to analyze the health data for
      decision-making processes, the solution also provided end-users with the ability
      to automatically track public health parameters. DISCUSSION: A large amount of
      data is collected and stored by various health care organizations at the local,
      state, and national levels. If utilized properly, such data can go a long way in
      optimizing health care services. CBI systems provide health care organizations
      with valuable insights for improving patient care, tracking trends for medical
      research, and for controlling costs. CONCLUSION: The CBI system has been found
      quite effective in bridging the gap between Florida's healthcare stake holders
      and FHDW health data. Consequently, the solution has improved in the planning and
      coordination of health care services for the state of Florida.

PMID- 25379129
TI  - An effective tool to manage the distribution of medicines and monitor the
      treatment in hospital pharmacies.
AB  - Introduction The purpose of the article is to share a modus operandi and a tool
      that allows the recruitment and management of thousands of patients and their
      treatment by using a simple software created by the author and made freely
      available to all colleague-pharmacists. The author, a pharmacist, created this
      database because there were no tools on the market with all the features needed
      to manage the treatment of patients and the orders of drugs to ensure continuity
      of care without waste of public money. Methods The data collection is facilitated
      by the software and allows the monitoring of treatment of the patients and their
      re-evaluation. This tool can create a table containing all the information needed
      to predict the demand for drugs, the timing of therapies and of the treatment
      plans. It is an effective instrument to calculate the optimal purchase of drugs
      and the delivery of therapies to patients. Conclusions A simple tool that allows
      the management of many patients, reduces research time and facilitates the
      control of therapies. It allows us to optimize inventory and minimize the stock
      of drugs. It allows the pharmacist to focus attention on the clinical management
      of the patient by helping him to follow therapy and respond to his needs. 

PMID- 25379130
TI  - Community based research network: opportunities for coordination of care, public
      health surveillance, and farmworker research.
AB  - INTRODUCTION: The lack of aggregated longitudinal health data on farmworkers has
      severely limited opportunities to conduct research to improve their health
      status. To correct this problem, we have created the infrastructure necessary to
      develop and maintain a national Research Data Repository of migrant and seasonal
      farmworker patients and other community members receiving medical care from
      Community and Migrant Health Centers (C/MHCs). Project specific research
      databases can be easily extracted from this repository. METHODS: The Community
      Based Research Network (CBRN) has securely imported and merged electronic health
      records (EHRs) data from five geographically dispersed C/MHCs. To demonstrate the
      effectiveness of our data aggregation methodologies, we also conducted a small
      pilot study using clinical, laboratory and demographic data from the CBRN Data
      Repository from two initial C/MHCs to evaluate HbA1c management. RESULTS:
      Overall, there were 67,878 total patients (2,858 farmworkers) that were seen by
      two C/MHCs from January to August 2013. A total of 94,189 encounters were
      captured and all could be linked to a unique patient. HbA1c values decreased as
      the number of tests or intensity of testing increased. CONCLUSION: This project
      will inform the foundation for an expanding collection of C/MHC data for use by
      clinicians for medical care coordination, by clinics to assess quality of care,
      by public health agencies for surveillance, and by researchers under
      Institutional Review Board (IRB) oversight to advance understanding of the needs
      and capacity of the migrant and seasonal farmworker population and the health
      centers that serve them. Approved researchers can request data that constitute a
      Limited Data Set from the CBRN Data Repository to establish a specific research
      database for their project.

PMID- 25379131
TI  - Molecular detection of virulence genes as markers in Pseudomonas aeruginosa
      isolated from urinary tract infections.
AB  - Catheter associated urinary tract infections by P. aeruginosa are related to
      variety of complications. Quorum sensing and related circuitry guard its
      virulence potential. Though P. aeruginosa accounts for an appreciable amount of
      virulence factors, this organism is highly unstable phenotypically. Thus,
      genotyping of clinical isolates of P. aeruginosa is of utmost importance for
      understanding the epidemiology of infection. This may contribute towards
      development of immunotherapeutic approaches against this multi drug resistant
      pathogen. Moreover, no epidemiological study has been reported yet on uroisolates
      of P. aeruginosa. Thus this study was planned to obtain information regarding
      presence, distribution and rate of occurrence of quorum sensing and some
      associated virulence genes at genetic level. The profiling of quorum sensing
      genes lasI, lasR, rhlI, rhlR and virulence genes like toxA, aprA, rhlAB, plcH,
      lasB and fliC of twelve strains of P. aeruginosa isolated from patients with UTIs
      was done by direct PCR. The results showed variable distribution of quorum
      sensing genes and virulence genes. Their percentage occurrence may be
      specifically associated with different levels of intrinsic virulence and
      pathogenicity in urinary tract. Such information can help in identifying these
      virulence genes as useful diagnostic markers for clinical P. aeruginosa strains
      isolated from UTIs. 

PMID- 25379132
TI  - Genetic and epigenetic analysis of monozygotic twins discordant for testicular
      cancer.
AB  - Despite the notion that monozygotic (identical) twins share 100% identical
      genetic information, genetic differences among monozygotic twin pairs do occur
      and can be explained by mechanisms occurring during post-zygotic events. Despite
      such twins being fundamentally "identical", these post-zygotic genetic changes
      may give rise to phenotypic differences and genetic diseases. Consequently,
      studies of monozygotic twin pairs discordant for specific genetic diseases
      represent an important tool for the identification of disease genes. We used
      array comparative genomic hybridization (aCGH) and methylation arrays to search
      for genetic and epigenetic differences in blood drawn from four monozygotic twin
      pairs discordant for testicular germ cell tumors. No consistent differences were
      identified. A larger twin study would be required to achieve confident discovery
      of very subtle differences between monozygotic twins discordant for testicular
      germ cell tumors. 

PMID- 25379133
TI  - Polycyclic aromatic hydrocarbons and risk of gastric cancer in the Shanghai
      Women's Health Study.
AB  - PURPOSE: Polycyclic aromatic hydrocarbons (PAHs) are byproducts of incomplete
      combustion of organic materials. Sources include tobacco smoke, charbroiled meat,
      and air pollution. Indirect evidence suggests that PAHs may be associated with
      carcinogenesis, but the association with gastric cancer is unclear. METHODS:
      Using a nested case-control study design, we examined prediagnostic urinary
      concentrations of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite, in 153
      gastric cancer cases and 306 matched controls within the Shanghai Women's Health
      Study. Conditional logistic regression adjusted for potential risk factors was
      used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).
      RESULTS: Urinary 1-OHPG concentrations were slightly higher among cases than
      controls, with medians of 0.29 MUmol/mol Cr (interquartile range, 0.16-0.48) and
      0.24 MUmol/mol Cr (interquartile range, 0.12-0.45), respectively. Increasing
      concentrations of 1-OHPG appeared to be associated with elevated risk of gastric
      cancer, but not within the highest category of 1-OHPG (Q4 vs Q1: OR = 1.4; 95% CI
      = 0.8-2.5). CONCLUSIONS: Our findings suggest that higher concentrations of 1
      OHPG are related to gastric cancer risk, but no clear dose-response relationship
      was observed.

PMID- 25379134
TI  - Genetic variants in anti-Mullerian hormone and anti-Mullerian hormone receptor
      genes and breast cancer risk in Caucasians and African Americans.
AB  - Anti-Mullerian hormone (AMH) regulates ovarian folliculogenesis by signaling via
      its receptors, and elevated serum AMH levels are associated with an increased
      risk of breast cancer. No previous studies have examined the effects of genetic
      variants in AMH-related genes on breast cancer risk. We evaluated the
      associations of 62 single nucleotide polymorphisms (SNPs) in AMH and its receptor
      genes, including AMH type 1 receptor (ACVR1) and AMH type 2 receptor (AMHR2),
      with the risk of breast cancer in the Women's Insights and Shared Experiences
      (WISE) Study of Caucasians (346 cases and 442 controls), as well as African
      Americans (149 cases and 246 controls). Of the 62 SNPs evaluated, two showed a
      nominal significant association (P for trend < 0.05) with breast cancer risk
      among Caucasians, and another two among African Americans. The age-adjusted
      additive odds ratios (ORs) (95% confidence interval (95% CI)) of those two SNPs
      (ACVR1 rs12694937[C] and ACVR1 rs2883605[T]) for the risk of breast cancer among
      Caucasian women were 2.33 (1.20-4.52) and 0.68 (0.47-0.98), respectively. The age
      adjusted additive ORs (95% CI) of those two SNPs (ACVR1 rs1146031[G] and AMHR2
      functional SNP rs2002555[G]) for the risk of breast cancer among African American
      women were 0.63 (0.44-0.92) and 1.67 (1.10-2.53), respectively. However, these
      SNPs did not show significant associations after correction for multiple testing.
      Our findings do not provide strong supportive evidence for the contribution of
      genetic variants in AMH-related genes to the risk of developing breast cancer in
      either Caucasians or African Americans. 

PMID- 25379135
TI  - Determinants of concentrations of N(epsilon)-carboxymethyl-lysine and soluble
      receptor for advanced glycation end products and their associations with risk of
      pancreatic cancer.
AB  - The soluble receptor for advanced glycation end-products (sRAGE) is shown to
      mitigate pro-inflammatory effects triggered by ligation of RAGE with N(epsilon)
      carboxymethyl-lysine (CML)-AGE or other ligands. We examined the associations
      among host, lifestyle, and genetic determinants of CML-AGE or sRAGE and risk of
      pancreatic cancer in the prospective ATBC Study. We obtained baseline exposure
      information, data on serological and genetic biomarkers from 141 patients with
      pancreatic cancer and 141 subcohort controls. Stepwise linear and logistic
      regression models were used for data analysis. Multiple linear regression
      analyses showed that CML-AGE concentrations were independently inversely
      correlated with the minor allele of rs640742 of DDOST, physical activity, alcohol
      consumption, diastolic blood pressure (BP), and positively correlated with heart
      rate, serum sRAGE and HDL concentrations (P < 0.05). sRAGE concentrations were
      independently inversely correlated with the 82Ser allele of rs2070600 of RAGE,
      age, body mass index, heart rate, and serum HDL; and positively correlated with
      serum CML-AGE, sucrose consumption, and diastolic BP (P < 0.05). The minor allele
      of rs1035786 of RAGE was associated with reduced risk of pancreatic cancer (any T
      compared with CC: multivariate OR = 0.61, 95% CI: 0.38-0.98). We identified host
      metabolic profile, lifestyle and genetic factors that explained approximately 50%
      of variability of CML-AGE or sRAGE in Finnish men smokers. The association
      between RAGE SNPs and pancreatic cancer risk warrants further investigation. 

PMID- 25379136
TI  - Sex hormone pathway gene polymorphisms are associated with risk of advanced
      hepatitis C-related liver disease in males.
AB  - BACKGROUND: Males have excess advanced liver disease and cirrhosis risk including
      from chronic hepatitis C virus (HCV) infection though the reasons are unclear.
      GOAL: To examine the role variants in genes involved in androgen and estrogen
      biosynthesis and metabolism play in HCV-related liver disease risk in males.
      METHODS: We performed a cross-sectional study evaluating single nucleotide
      polymorphisms (SNPs) in 16 candidate genes involved in androgen and estrogen
      ligand and receptor synthesis and risk of advanced hepatic fibrosis (F3/F4-F4)
      and inflammation (A2/A3-A3). We calculated adjusted odds ratios (ORs) using
      logistic regression and used multifactor dimensionality reduction (MDR) analysis
      to assess for gene-environment interaction. RESULTS: Among 466 chronically HCV
      infected males, 59% (n = 274) had advanced fibrosis and 54% (n = 252) had
      advanced inflammation. Nine of 472 SNPs were significantly associated with
      fibrosis risk; 4 in AKR1C3 (e.g., AKR1C3 rs2186174: ORadj = 2.04, 95% CI 1.38
      3.02), 1 each in AKR1C2 and ESR1, and 1 in HSD17B6. Four SNPs were associated
      with inflammation risk, 2 in SRD5A1 (e.g., SRD5A1 rs248800: ORadj = 1.86, 95% CI
      1.20-2.88) and 1 each in AKR1C2 and AKR1C3. MDR analysis identified a single
      AKR1C3 locus (rs2186174) as the best model for advanced fibrosis; while a 4-locus
      model with diabetes, AKR1C2 rs12414884, SRD5A1 rs6555406, and SRD5A1 rs248800 was
      best for inflammation. CONCLUSIONS: The consistency of our findings suggests
      AKR1C isoenzymes 2 and 3, and potentially SRD5A1, may play a role in progression
      of HCV-related liver disease in males. Future studies are needed to validate
      these findings and to assess if similar associations exist in females.

PMID- 25379137
TI  - Identification of a metabolic biomarker panel in rats for prediction of acute and
      idiosyncratic hepatotoxicity.
AB  - It has been estimated that 10% of acute liver failure is due to "idiosyncratic
      hepatotoxicity". The inability to identify such compounds with classical
      preclinical markers of hepatotoxicity has driven the need to discover a mechanism
      based biomarker panel for hepatotoxicity. Seven compounds were included in this
      study: two overt hepatotoxicants (acetaminophen and carbon tetrachloride), two
      idiosyncratic hepatotoxicants (felbamate and dantrolene), and three non
      hepatotoxicants (meloxicam, penicillin and metformin). Male Sprague-Dawley rats
      were orally gavaged with a single dose of vehicle, low dose or high dose of the
      compounds. At 6 h and 24 h post-dosing, blood was collected for metabolomics and
      clinical chemistry analyses, while organs were collected for histopathology
      analysis. Forty-one metabolites from previous hepatotoxicity studies were semi
      quantified and were used to build models to predict hepatotoxicity. The selected
      metabolites were involved in various pathways, which have been noted to be linked
      to the underlying mechanisms of hepatotoxicity. PLS models based on all 41
      metabolite or smaller subsets of 6 (6 h), 7 (24 h) and 20 (6 h and 24 h)
      metabolites resulted in models with an accuracy of at least 97.4% for the hold
      out test set and 100% for training sets. When applied to the external test sets,
      the PLS models predicted that 1 of 9 rats at both 6 h and 24 h treated with
      idiosyncratic liver toxicants was exposed to a hepatotoxic chemical. In
      conclusion, the biomarker panel might provide information that along with other
      endpoint data (e.g., transcriptomics and proteomics) may diagnose acute and
      idiosyncratic hepatotoxicity in a clinical setting. 

PMID- 25379138
TI  - Using biological networks to improve our understanding of infectious diseases.
AB  - Infectious diseases are the leading cause of death, particularly in developing
      countries. Although many drugs are available for treating the most common
      infectious diseases, in many cases the mechanism of action of these drugs or even
      their targets in the pathogen remain unknown. In addition, the key factors or
      processes in pathogens that facilitate infection and disease progression are
      often not well understood. Since proteins do not work in isolation, understanding
      biological systems requires a better understanding of the interconnectivity
      between proteins in different pathways and processes, which includes both
      physical and other functional interactions. Such biological networks can be
      generated within organisms or between organisms sharing a common environment
      using experimental data and computational predictions. Though different data
      sources provide different levels of accuracy, confidence in interactions can be
      measured using interaction scores. Connections between interacting proteins in
      biological networks can be represented as graphs and edges, and thus studied
      using existing algorithms and tools from graph theory. There are many different
      applications of biological networks, and here we discuss three such applications,
      specifically applied to the infectious disease tuberculosis, with its causative
      agent Mycobacterium tuberculosis and host, Homo sapiens. The applications include
      the use of the networks for function prediction, comparison of networks for
      evolutionary studies, and the generation and use of host-pathogen interaction
      networks. 

PMID- 25379139
TI  - The biological networks in studying cell signal transduction complexity: The
      examples of sperm capacitation and of endocannabinoid system.
AB  - Cellular signal transduction is a complex phenomenon, which plays a central role
      in cell surviving and adaptation. The great amount of molecular data to date
      present in literature, together with the adoption of high throughput
      technologies, on the one hand, made available to scientists an enormous quantity
      of information, on the other hand, failed to provide a parallel increase in the
      understanding of biological events. In this context, a new discipline arose, the
      systems biology, aimed to manage the information with a computational modeling
      based approach. In particular, the use of biological networks has allowed the
      making of huge progress in this field. HERE WE DISCUSS TWO POSSIBLE APPLICATION
      OF THE USE OF BIOLOGICAL NETWORKS TO EXPLORE CELL SIGNALING: the study of the
      architecture of signaling systems that cooperate in determining the acquisition
      of a complex cellular function (as it is the case of the process of activation of
      spermatozoa) and the organization of a single specific signaling systems
      expressed by different cells in different tissues (i.e. the endocannabinoid
      system). In both the cases we have found that the networks follow a scale free
      and small world topology, likely due to the evolutionary advantage of robustness
      against random damages, fastness and specific of information processing, and easy
      navigability. 

PMID- 25379140
TI  - The role of protein interaction networks in systems biomedicine.
AB  - The challenging task of studying and modeling complex dynamics of biological
      systems in order to describe various human diseases has gathered great interest
      in recent years. Major biological processes are mediated through protein
      interactions, hence there is a need to understand the chaotic network that forms
      these processes in pursuance of understanding human diseases. The applications of
      protein interaction networks to disease datasets allow the identification of
      genes and proteins associated with diseases, the study of network properties,
      identification of subnetworks, and network-based disease gene classification.
      Although various protein interaction network analysis strategies have been
      employed, grand challenges are still existing. Global understanding of protein
      interaction networks via integration of high-throughput functional genomics data
      from different levels will allow researchers to examine the disease pathways and
      identify strategies to control them. As a result, it seems likely that more
      personalized, more accurate and more rapid disease gene diagnostic techniques
      will be devised in the future, as well as novel strategies that are more
      personalized. This mini-review summarizes the current practice of protein
      interaction networks in medical research as well as challenges to be overcome. 

PMID- 25379141
TI  - Computational approaches to metabolic engineering utilizing systems biology and
      synthetic biology.
AB  - Metabolic engineering modifies cellular function to address various biochemical
      applications. Underlying metabolic engineering efforts are a host of tools and
      knowledge that are integrated to enable successful outcomes. Concurrent
      development of computational and experimental tools has enabled different
      approaches to metabolic engineering. One approach is to leverage knowledge and
      computational tools to prospectively predict designs to achieve the desired
      outcome. An alternative approach is to utilize combinatorial experimental tools
      to empirically explore the range of cellular function and to screen for desired
      traits. This mini-review focuses on computational systems biology and synthetic
      biology tools that can be used in combination for prospective in silico strain
      design. 

PMID- 25379143
TI  - 3D representations of amino acids-applications to protein sequence comparison and
      classification.
AB  - The amino acid sequence of a protein is the key to understanding its structure
      and ultimately its function in the cell. This paper addresses the fundamental
      issue of encoding amino acids in ways that the representation of such a protein
      sequence facilitates the decoding of its information content. We show that a
      feature-based representation in a three-dimensional (3D) space derived from amino
      acid substitution matrices provides an adequate representation that can be used
      for direct comparison of protein sequences based on geometry. We measure the
      performance of such a representation in the context of the protein structural
      fold prediction problem. We compare the results of classifying different sets of
      proteins belonging to distinct structural folds against classifications of the
      same proteins obtained from sequence alone or directly from structural
      information. We find that sequence alone performs poorly as a structure
      classifier. We show in contrast that the use of the three dimensional
      representation of the sequences significantly improves the classification
      accuracy. We conclude with a discussion of the current limitations of such a
      representation and with a description of potential improvements. 

PMID- 25379142
TI  - Current advances in systems and integrative biology.
AB  - Systems biology has gained a tremendous amount of interest in the last few years.
      This is partly due to the realization that traditional approaches focusing only
      on a few molecules at a time cannot describe the impact of aberrant or modulated
      molecular environments across a whole system. Furthermore, a hypothesis-driven
      study aims to prove or disprove its postulations, whereas a hypothesis-free
      systems approach can yield an unbiased and novel testable hypothesis as an end
      result. This latter approach foregoes assumptions which predict how a biological
      system should react to an altered microenvironment within a cellular context,
      across a tissue or impacting on distant organs. Additionally, re-use of existing
      data by systematic data mining and re-stratification, one of the cornerstones of
      integrative systems biology, is also gaining attention. While tremendous efforts
      using a systems methodology have already yielded excellent results, it is
      apparent that a lack of suitable analytic tools and purpose-built databases poses
      a major bottleneck in applying a systematic workflow. This review addresses the
      current approaches used in systems analysis and obstacles often encountered in
      large-scale data analysis and integration which tend to go unnoticed, but have a
      direct impact on the final outcome of a systems approach. Its wide applicability,
      ranging from basic research, disease descriptors, pharmacological studies, to
      personalized medicine, makes this emerging approach well suited to address
      biological and medical questions where conventional methods are not ideal. 

PMID- 25379144
TI  - Methods for integration of transcriptomic data in genome-scale metabolic models.
AB  - Several computational methods have been developed that integrate transcriptomic
      data with genome-scale metabolic reconstructions to infer condition-specific
      system-wide intracellular metabolic flux distributions. In this mini-review, we
      describe each of these methods published to date with categorizing them based on
      four different grouping criteria (requirement for multiple gene expression
      datasets as input, requirement for a threshold to define a gene's high and low
      expression, requirement for a priori assumption of an appropriate objective
      function, and validation of predicted fluxes directly against measured
      intracellular fluxes). Then, we recommend which group of methods would be more
      suitable from a practical perspective. 

PMID- 25379145
TI  - Characterization of self-assembled DNA concatemers from synthetic
      oligonucleotides.
AB  - Studies of DNA-ligand interaction on a single molecule level provide
      opportunities to understand individual behavior of molecules. Construction of DNA
      molecules with repetitive copies of the same segments of sequences linked in
      series could be helpful for enhancing the interaction possibility for sequence
      specific binding ligand to DNA. Here we report on the use of synthetic
      oligonucleotides to self-assembly into duplex DNA concatemeric molecules. Two
      strands of synthetic oligonucleotides used here were designed with 50-mer in
      length and the sequences are semi-complimentary so to hybridize spontaneously
      into concatemers of double stranded DNA. In order to optimize the length of the
      concatemers the oligonucleotides were incubated at different oligomer
      concentrations, ionic strengths and temperatures for different durations.
      Increasing the salt concentration to 200 mM NaCl was found to be the major
      optimizing factor because at this enhanced ionic strength the concatemers formed
      most quickly and the other parameters had no detectable effect. The size and
      shape of formed DNA concatemers were studied by gel electrophoresis in agarose,
      polyacrylamide gels and by AFM. Our results show that linear DNA constructs up to
      several hundred base pairs were formed and could be separated from a substantial
      fraction of non-linear constructs. 

PMID- 25379148
TI  - The CROWN Initiative: Journal Editors Invite Researchers to Develop Core Outcomes
      in Women's Health.

PMID- 25379149
TI  - The Luteal Phase after GnRHa Trigger-Understanding An Enigma.
AB  - The luteal phase of all stimulated in vitro fertilization/intra-cytoplasmic sperm
      injection (IVF/ICSI) cycles is disrupted, which makes luteal phase support (LPS)
      mandatory. The cause of the disruption is thought to be the multifollicular
      development achieved during ovarian stimulation which results in
      supraphysiological concentrations of steroids se- creted by a high number of
      corpora lutea during the early luteal phase. This will directly inhibit
      luteinizing hormone (LH) secretion by the pituitary via negative feedback at the
      level of the hypothalamic-pituitary axis, leading to a luteal phase defect. With
      the intro- duction of the gonadotropin-releasing hormone (GnRH) antagonist
      protocol, it became feasible to trigger final oocyte maturation and ovulation
      with a single bolus of GnRH agonist (GnRHa) as an alternative to human chorionic
      gonadotropin (hCG). GnRHa trig- gering presents several advantages, including the
      reduction in or even elimination of ovarian hyperstimulation syndrome. Despite
      the potential advantages of GnRHa trig- gering, previous randomized controlled
      trials reported a poor clinical outcome with high rates of early pregnancy
      losses, despite supplementation with a standard LPS in the form of progesterone
      and estradiol. Following these disappointing results, several studies now report
      a luteal phase rescue after modifications of the LPS, resulting in a reproductive
      outcome comparable to that seen after hCG triggering. We herein review luteal
      phase dif- ferences between the natural cycle, hCG trigger and GnRHa trigger and
      present the most recent data on handling the luteal phase after GnRHa triggering.

PMID- 25379147
TI  - A review of metabolic and enzymatic engineering strategies for designing and
      optimizing performance of microbial cell factories.
AB  - Microbial cell factories (MCFs) are of considerable interest to convert low value
      renewable substrates to biofuels and high value chemicals. This review highlights
      the progress of computational models for the rational design of an MCF to produce
      a target bio-commodity. In particular, the rational design of an MCF involves:
      (i) product selection, (ii) de novo biosynthetic pathway identification (i.e.,
      rational, heterologous, or artificial), (iii) MCF chassis selection, (iv) enzyme
      engineering of promiscuity to enable the formation of new products, and (v)
      metabolic engineering to ensure optimal use of the pathway by the MCF host.
      Computational tools such as (i) de novo biosynthetic pathway builders, (ii)
      docking, (iii) molecular dynamics (MD) and steered MD (SMD), and (iv) genome
      scale metabolic flux modeling all play critical roles in the rational design of
      an MCF. Genome-scale metabolic flux models are of considerable use to the design
      process since they can reveal metabolic capabilities of MCF hosts. These can be
      used for host selection as well as optimizing precursors and cofactors of
      artificial de novo biosynthetic pathways. In addition, recent advances in genome
      scale modeling have enabled the derivation of metabolic engineering strategies,
      which can be implemented using the genomic tools reviewed here as well. 

PMID- 25379150
TI  - Pregnancy rate following luteal phase support in Iranian women with polycystic
      ovarian syndrome.
AB  - BACKGROUND: To assess the efficacy of luteal phase support (LPS) using
      intravaginal progesterone (P) on pregnancy rate in Iranian women with polycystic
      ovarian syndrome (PCOS) who used a combination for ovulation induction consisting
      of letrozole or clomi- phene citrate (CC) and human menopausal gonadotropin
      (HMG). MATERIALS AND METHODS: This was a randomized clinical trial undertaken in
      a fertility clinic in Kashan, Isfahan Province, Iran. A total of 198 patients
      completed treatment and follow up. Base on chosen ovulation induction programs,
      they were divided into two following group: i. CC group (n=98) used a combination
      consisting of CC (100 mg*5 day) and HMG (150 IU*5 day) and ii. letrozole group
      (n=100) used a combination consisting of letrozole (5 mg*5 day) and HMG (150 IU*5
      day). After human chorionic gonadotropin (hCG) administration (5000 IU), the
      patients (n=122) who randomly re- ceived intravaginal P (Cyclogest, 400 mg daily)
      were included in LPS group, while the rest (n=123) were included in non-P cycles
      group. The outcome was the comparison of chemical pregnancy rate between the
      groups. RESULTS: Our findings showed that LPS was associated with a 10% higher
      pregnancy rate than in non-P cycles, although this difference did not reach
      statistical significant (p=0.08). LPS improved pregnancy rate in both CC (4%) and
      letrozole (6%) groups. In addition, patients who used letrozole for ovulation
      induction along with intravaginal P showed higher pregnancy rates than CC group.
      CONCLUSION: Administration of vaginal P for LPS may improve the pregnancy rate in
      women with PCOS using letrozole or CC in combination with HMG for ovulation induc
      tion (Registration Number: IRCT201206072967N4).

PMID- 25379146
TI  - Proteomics for systems toxicology.
AB  - Current toxicology studies frequently lack measurements at molecular resolution
      to enable a more mechanism-based and predictive toxicological assessment.
      Recently, a systems toxicology assessment framework has been proposed, which
      combines conventional toxicological assessment strategies with system-wide
      measurement methods and computational analysis approaches from the field of
      systems biology. Proteomic measurements are an integral component of this
      integrative strategy because protein alterations closely mirror biological
      effects, such as biological stress responses or global tissue alterations. Here,
      we provide an overview of the technical foundations and highlight select
      applications of proteomics for systems toxicology studies. With a focus on mass
      spectrometry-based proteomics, we summarize the experimental methods for
      quantitative proteomics and describe the computational approaches used to derive
      biological/mechanistic insights from these datasets. To illustrate how proteomics
      has been successfully employed to address mechanistic questions in toxicology, we
      summarized several case studies. Overall, we provide the technical and conceptual
      foundation for the integration of proteomic measurements in a more comprehensive
      systems toxicology assessment framework. We conclude that, owing to the critical
      importance of protein-level measurements and recent technological advances,
      proteomics will be an integral part of integrative systems toxicology approaches
      in the future. 

PMID- 25379151
TI  - Effect of Piroxicam on ART Outcome: A Pilot Study.
AB  - BACKGROUND: One of the most important factors affecting success rates in assisted
      reproductive techniques (ART) besides the number of oocytes retrieved and high
      quality embryos derived from them is the technical aspects of embryo transfer. It
      seems that pretreatement with uterine relaxants can be helpful in preventing un-
      pleasant cramps which can have an adverse effect on ART outcome. In this respect,
      some drugs such as prostaglandin inhibitors or sedatives have been evaluated but
      not confirmed yet remain controversial. This study was performed in order to
      assess the effect of administrating Piroxicam prior to embryo transfer on
      pregnancy rates in ART cycles. MATERIALS AND METHODS: This pilot study was
      performed from August 2010 through December 2011 on 50 infertile women in ART
      cycles. Recombinant follicle stimulating hormone (rFSH) with a long gonadotropin
      releasing hormone (GnRH) analogue protocol were used for controlled ovarian
      hyperstimulation. The subjects were randomly allocated into two groups of 25
      patients after obtaining written consent. Group A received a 10 mg Piroxicam
      capsule 30 minutes before embryo transfer and group B was the control group with
      no treatment. Data were analyzed by Chi-square and analysis of variance (ANOVA).
      RESULTS: Pregnancy rate was 34% (n=17) totally, with 32% (n=8) in group A and 36%
      (n=9) in group B (p=0.75). Uterine cramps were experienced by 4 women (16%) in
      group B, while none were reported by women in group A (p=0.037). CONCLUSION: It
      seems that Piroxicam administration 30 minutes prior to embryo transfer can- not
      increase pregnancy rates, but can prevent or reduce uterine cramps after the
      procedure.

PMID- 25379152
TI  - Comparison between Conventional Blind Embryo Transfer and Embryo Transfer Based
      on Previously Measured Uterine Length.
AB  - BACKGROUND: Embryo transfer (ET) is one of the most important steps in assisted
      re- productive technology (ART) cycles and affected by many factors namely the
      depth of embryo deposition in uterus. In this study, the outcomes of
      intracytoplasmic sperm injec- tion (ICSI) cycles after blind embryo transfer and
      embryo transfer based on previously measured uterine length using vaginal
      ultrasound were compared. MATERIALS AND METHODS: This prospective randomised
      clinical trial included one hun- dred and forty non-donor fresh embryo transfers
      during January 2010 to June 2011. In group I, ET was performed using conventional
      (blind) method at 5-6cm from the external os, and in group II, ET was done at a
      depth of 1-1.5 cm from the uterine fundus based on previously measured uterine
      length using vaginal sonography. Appropriate statistical analysis was performed
      using Student's t test and Chi-square or Fisher's exact test. The software that
      we used was PASW statistics version 18. A p value <0.05 was considered
      statistically significant. RESULTS: Chemical pregnancy rate was 28.7% in group I
      and 42.1% in group II, while the difference was not statistically significant
      (p=0.105). Clinical pregnancy, ongoing preg- nancy and implantation rates for
      group I were 21.2%, 17.7%, and 12.8%, while for group II were 33.9%, 33.9%, and
      22.1, respectively. In group I and group II, abortion rates were 34.7% and 0%,
      respectively, indicating a statistically significant difference (p<0.005). No
      ectopic pregnancy occurred in two groups. CONCLUSION: The use of uterine length
      measurement during treatment cycle in order to place embryos at depth of 1-1.5cm
      from fundus significantly increases clinical and ongo- ing pregnancy and
      implantation rates, while leads to a decrease in abortion rate (Registra- tion
      Number: IRCT2014032512494N1).

PMID- 25379153
TI  - Age, body mass index, and number of previous trials: are they prognosticators of
      intra-uterine-insemination for infertility treatment?
AB  - BACKGROUND: To examine whether pregnancy rate (PR) of intrauterine insemination
      (IUI) is related to certain demographic factors, such as age and body mass index
      (BMI), along with number of IUI cycles performed, a set of infertile Saudi women.
      MATERIALS AND METHODS: During this prospective study (a 24-month period), 301
      Saudi women with infertility underwent IUI in our infertility clinic. We
      investigated whether PR is correlated with patient age and BMI, and the number of
      IUI trials, in order to determine if they could be used as prognosticators of
      pregnancy success. RESULTS: The highest PR was 14.89% for ages 19-25 and the
      lowest PR was 4.16% for ages 41-45, indicating no statistically significant
      difference among PR in all age groups (p value of 0.225). Also, in terms of BMI,
      the highest PR was 13.04% for BMI >=35 and the lowest was 7.84% for BMI of <25 to
      18.5, indicating no significant difference among different BMI groups (p value of
      0.788). One-cycle treatment, as expected, was more successful (PR=12.84%) than 2
      cycle treatment (PR=5.75%), however, 3-5-cycles treatment still showed
      encouraging results (PR=17.24%); but the difference did not reach statistical
      significance (p value=0.167). CONCLUSION: PR after IUI treatment remained
      approximately 10% from 19 to 40 years of age and declined after 40. Although no
      significant difference was observed among different age groups, earlier treatment
      is still recommended. There was a positive but not statistically significant
      correlation between PR and patient's BMI indicating that BMI is not a determining
      factor. There was also no correlation between PR and number of IUI trials.
      Patients can thus try as many times as they want before moving on to in vitro
      fertilization (IVF) treatment.

PMID- 25379154
TI  - Polycystic ovary syndrome in university students: occurrence and associated
      factors.
AB  - BACKGROUND: The aim of this study was to assess the occurrence of polycystic
      ovary syndrome (PCOS) and its association with body composition among students in
      University of Sharjah (UOS). MATERIALS AND METHODS: This cross-sectional study
      included a total sample size of 50 female students registering in undergraduate
      programs at the University of Sharjah using convenience sampling technique. A
      pretested interview schedule was administered to elicit information pertaining to
      personal background and medical history related to PCOS. A diag- nostic
      ultrasound scan was performed for determining PCOS along with a body composition
      analysis using bioelectrical impedance analysis (BIA) technology. RESULTS: Twenty
      percent (10 out of 50 participants) were diagnosed with PCOS, of whom only 4
      individuals were previously diagnosed with PCOS and aware of their conditions,
      while the reports showed 16% with oligomenorrhea, 4% with polymenorrhea, and none
      with amen- orrhea. A positive family history was indicated as reported by 22% of
      the total participants. Significant difference between the body weights of
      participants having PCOS (66.7 kg) and those without it (58.8 kg) were noted
      (p=0.043, t=2.084). On the other hand, the body compo- sition related variables
      including waist-hip ratio (WHR), fat-free mass (FFM), percent body fat (PBF) and
      visceral fat area (VFA) were relatively higher in participants having PCOS than
      those without it. However, there was no statistical significance of differences.
      Comparatively, the participants with PCOS had lower bone mineral density (BMD)
      than those without it, whereas the difference was statistically non-significant.
      CONCLUSION: The occurrence of PCOS in the present study is consistent with the
      global preva- lence. Comparatively, the body composition of PCOS females is
      different from the normal fe- males. Further studies are required in the Middle
      East region on larger sample sizes and broader aspects of health including
      lifestyle and dietary components to understand these differences.

PMID- 25379155
TI  - Age at Menopause and Its Main Predictors among Iranian Women.
AB  - BACKGROUND: Since time of menopause is influenced by a variety of racial,
      environmental, and physiological factors, determining age at natural menopause
      and its main indicators seems to be necessary. The present study attempted to
      determine average age at menopause and its main predictors among Iranian women.
      MATERIALS AND METHODS: This descriptive-analytic study was carried out on 400
      postmenopausal women aged 43 to 65 years attending the health centers in Hamadan,
      Hamadan Province, Iran, during 2013. Due to potential effects of oral
      contraceptive pills (OCP) on age of menopause, we considered two groups of women
      with and without OCP use using cluster sampling method. Data were collected
      through individual interviews at the health centers. RESULTS: The findings showed
      significant univariate relationships between age at menopause with some baseline
      variables including mother's age at menopause (p<0.001), mother and spouse with
      high educational level (p<0.001), passive cigarette smoking (p<0.001), weekly
      physical activity (p<0.001), and high family income (p<001). Adversely, smoking
      was associated with early menopause. CONCLUSION: The postmenopausal women doing
      intense weekly physical activity, having mothers with late menopause, having
      higher monthly income, and experiencing later-age pregnancy are likely to reach
      menopause later than their contemporaries, while smokers have an early menopause.

PMID- 25379156
TI  - Sexual Functioning among Married Iranian Women with Polycystic Ovary Syndrome.
AB  - BACKGROUND: This study aimed to assess sexual functioning among women with
      polycystic ovary syndrome (PCOS) in Iran. MATERIALS AND METHODS: A cross
      sectional study was conducted to ascertain factors re- lated to sexual
      functioning in 300 PCOS patients attending to the private practice centers in
      Kashan, Isfahan Province, Iran, from May to October 2012. The Female Sexual
      Function Index (FSFI) was used to measure sexual functioning. Moreover, the socio
      demo-graphic details and clinical information of PCOS including obesity,
      hirsutism, acne, mestrual cycle disturbances, infertility and endocrine profile
      were recorded for each patient. RESULTS: Overall the prevalence of female sexual
      dysfunction (FSD) was 16.6%. In particular patients indicated poorer sexual
      functioning for the desire (48.3%) and the arousal (44.7%) subscales. Multiple
      logistic regression analysis suggested patients with lower educational level (OR:
      2.94; 95% CI: 1.46-5.92) and irregular menstrual status (OR: 4.61; 95% CI: 1.93
      11) were more likely to report sexual dysfunction. CONCLUSION: The findings
      suggest that desire and arousal were the most prevalent sexual disorders reported
      in this patient population. In addition, findings suggested that women with
      limited or no formal education and a history of menstrual irregularities were the
      most likely to report female sexual dysfunction. Further investigations are
      needed to examine female sexual functioning among women with PCOS, to educate
      their health care providers, and to develop therapeutic interventions.

PMID- 25379157
TI  - The study of sexual satisfaction in Iranian women applying for divorce.
AB  - BACKGROUND: Marital instability is affected by many factors. In Iran, socio
      cultural and political limitations are obstacles for sexuality-related studies;
      therefore, insufficient in- formation is available in this area. In the present
      research, we investigated the relation- ship between marital instability and
      sexual satisfaction among Iranian women. MATERIALS AND METHODS: A case-control
      study was carried out to investigate women ap- plying for divorce in comparison
      with our controls during 2011 to 2012 in Isfahan, Iran. Data gathering was done
      using a questionnaire including two parts: socio-demographic information and
      factors influencing sexual satisfaction. Larson Inventory of Sexual Sat-
      isfaction for determining sexual satisfaction was used to determine sexual
      satisfaction. RESULTS: Divorce rate is significantly related to sexual
      satisfaction (p=0.009). There were also significant relationships between sexual
      satisfaction and the following variables: age, economic status, amount of income,
      duration of marriage, number of children, hous- ing, alcohol/drug abuse by
      spouse, being beaten by spouse, compulsory marriage, second marriage of spouse,
      and being happy with current partner. CONCLUSION: Sexual satisfaction plays an
      important role in marital stability of Iranian women. Thus, development of
      practical strategies in order to provide cultural intervention is needed to
      improve Iranian couples' awareness of their sexual relationship. Indeed, train-
      ings in communication skills through sexual encounters are essential.

PMID- 25379158
TI  - A Survey on Oocyte Donation: Turkish Fertile and Infertile Women's Opinions.
AB  - BACKGROUND: There are various treatment options for infertility, and new
      techniques are also being developed as it is an important healthcare problem
      affecting approximately 15-20% of married couples. The purpose of this study was
      to evaluate the level of infor- mation of fertile and infertile Turkish women on
      oocyte donation in order to understand their awareness of the legal, ethical,
      social and religious issues regarding this technique and to compare these two
      groups in terms of these variables. MATERIALS AND METHODS: This cross-sectional
      study included infertile women being treated at the assisted reproductive
      technologies (ART) program of a university hos- pital and women who had presented
      at the gynecology outpatients department of the same university for routine check
      ups and who had no previous history of infertility. After consulting with
      specialists in the field and searching the related literature, a data collection
      form having 22 questions for infertile women and 18 questions for fertile women
      was prepared. RESULTS: The women were asked whether they would use the oocytes of
      another woman if necessary. The results showed that 67.6% of the fertile women
      said they would never want to use this method, while 63.9% of the infertile women
      stated they may accept to use this method under certain conditions (two distinct
      answers appeared in the answers, some women stated they would prefer donated
      oocytes from close relatives, while others stated they would prefer oocytes from
      total strangers), such as from a close relative or from someone they do not know
      at all. CONCLUSION: Infertile women mentioned that they could use illegal routes
      if necessary to have a child at much higher rates than stated by fertile women.
      This shows that desire to have a child is a strong source of motivation in
      Turkey.

PMID- 25379159
TI  - The attitude of South korean people regarding usage of the internet perinatal
      consultation.
AB  - BACKGROUND: To the general public, the Internet is an acceptable method of
      obtaining information. It also plays an important role in guiding patients and
      solving their problems. We investigated the clinical characteristics of an
      Internet website to provide guidelines and tips for consultation. MATERIALS AND
      METHODS: In this retrospective observational study, we analyzed the use of a free
      public Internet perinatal consultation website provided by the Ministry of Health
      and Welfare of Korea. We evaluated 2,254 Internet perinatal consultations and
      assessments of prenatal and obstetrics from August 2006 to December 2009. We
      evaluated the patients' questions based on Williams' textbook categories and
      their clinical characteristics. RESULTS: The mean age of patients seeking
      consultation was 33.9 +/- 13.2 years, and parity was 1.2 +/- 0.5. The most
      commonly asked questions were about drug safety during pregnancy (20.4%), and
      questions regarding prenatal care (18.7%) and labor pain (15.4%) were the second
      and third most commonly asked questions, respectively. CONCLUSION: The Internet
      can provide good information to patients. Thus, guidelines regarding pregnancy
      related questions and answers should be created. Obstetricians could use our data
      to identify question tendencies.

PMID- 25379160
TI  - A Sectional Study: The Relationship between Perceived Social Support and
      Depression in Turkish Infertile Women.
AB  - BACKGROUND: Studies conducted on infertile women in the literature investigated
      some features such as depression, anxiety, loneliness, and social support.
      However, there has been no study examining the relationship between levels of
      perceived social support and depression in infertile women. Considering this
      deficiency, the study was conducted to determine the relationship between
      perceived social support and depression in infertile women. The purpose of this
      study is to determine the relationship between perceived social support and
      depression in infertile women. MATERIALS AND METHODS: This descriptive and
      sectional study was conducted between 16 April and 31 October 2012 in in vitro
      fertilisation (IVF) Centre of Firat University Re- search Hospital. Sampling
      formula was used in cases when the number of elements in the population was not
      known to calculate minimum sample size required to be included in the study. A
      total of 238 women who applied to the relevant centre between the specified dates
      constituted the sample group of the study. A Questionnaire Form, Beck Depression
      Inventory (BDI) and the Multidimensional Scale of Perceived Social Support
      (MSPSS) were used to collect the data. A pilot study was carried out on nine
      infertile women. As a result of the pilot study, we formed the final version of
      the Questionnaire Form. The data of these nine women were not involved in the
      research. The data obtained from the study was assessed using Statistical Package
      for the Social Sciences (SPSS; SPSS Inc., Chicago, IL, USA) version 15.0.
      Percentage distribution, mean, t test, one-way analysis of variance (One-Way
      ANOVA), and Pearson correlation analysis were used to evaluate the data. RESULTS:
      The women's total mean score on the BDI was 12.55 +/- 8.07. Scores obtained by
      women on the MSPSS was 15.75 +/- 8.53 for the subscale of friend, 21.52 +/- 8.20
      for the subscale of family, and 15.62 +/- 8.45 for the subscale of significant
      others. The women's total MSPSS score was 52.89 +/- 21.75. CONCLUSION: A
      significant, negative relationship was found between total BDI score with
      subscale and total mean scores of MSPSS (r= -0.596, p<0.01). Symptoms of
      depression decreased as the women's perceived social support increased.

PMID- 25379161
TI  - Infertile individuals' marital relationship status, happiness, and mental health:
      a causal model.
AB  - BACKGROUND: This study examined the causal model of relation between marital
      relation- ship status, happiness, and mental health in infertile individuals.
      MATERIALS AND METHODS: In this descriptive study, 155 subjects (men: 52 and
      women: 78), who had been visited in one of the infertility Centers, voluntarily
      participated in a self-evaluation. Golombok Rust Inventory of Marital Status,
      Oxford Happiness Ques- tionnaire, and General Health Questionnaire were used as
      instruments of the study. Data was analyzed by SPSS17 and Amos 5 software using
      descriptive statistics, independent sample t test, and path analysis. RESULTS:
      Disregarding the gender factor, marital relationship status was directly related
      to happiness (p<0.05) and happiness was directly related to mental health,
      (p<0.05). Also, indirect relation between marital relationship status and mental
      health was significant (p<0.05). These results were confirmed in women
      participants but in men participants only the direct relation between happiness
      and mental health was significant (p<0.05). CONCLUSION: Based on goodness of
      model fit in fitness indexes, happiness had a mediator role in relation between
      marital relationship status and mental health in infertile individu- als
      disregarding the gender factor. Also, considering the gender factor, only in
      infertile women, marital relationship status can directly and indirectly affect
      happiness and mental health.

PMID- 25379162
TI  - Effects of In Vitro Zinc Sulphate Additive to The Semen Extender on Water Buffalo
      (Bubalusbubalis) Spermatozoa before and after Freezing.
AB  - BACKGROUND: The objective of the study was to investigate the effects of in vitro
      zinc sulphate additive to semen extender on sperm parameters (progressive
      motility, viability, membrane integrity and DNA stability) after
      cryopreservation. MATERIALS AND METHODS: In this Prospective longitudinal
      laboratory study, semen samples of 5 buffalo bulls of 3-5 years old were
      collected at 5 different occasions from Iran, Urmia during summer and autumn
      2011, 25 samples were used in each treatment. Sperm progressive motility,
      viability and abnormal morphology were measured before and at 0.5 (T0), 1(T1) and
      2(T2) hours after diluting semen(1:10 v/v) in Tris-citric acid based extender
      (without egg yolk and glycerol) at 37C containing none (control group), 0.072,
      0.144, 0.288, 0.576 and 1.152 mg/L zinc sulphate to investigate dose and time
      effects. Next, a Tris-citric acid-egg yolk-glycerol extender (20% egg yolk and 7%
      glycerol) containing the same amount of zinc sulphate was prepared, diluted semen
      (1:10 v/v) was cooled and kept into a refrigerated chamber (4C) for 4 hours to
      equilibrate. Sperm progressive motility, viability, abnormal morphology, membrane
      integrity and DNA damage were estimated.The equilibrated semen was loaded in 0.5
      ml French straws and frozen in liquid nitrogen. Later, the frozen semen was
      thawed and the same parameters as well as total antioxidant capacity (TAC) of the
      frozen-thawed semen were determined. RESULTS: The results showed that zinc
      sulphate additive at the rate of 0.288 mg/L gave a higher protection of sperm
      progressive motility (53.7 +/- 1.8% vs. 40.5 +/- 1.7%), viability (70.8 +/- 1.8%
      vs. 60.1 +/- 1.5%), membrane integrity (67.3 +/- 1.6% vs. 56.6 +/- 1.7%), DNA
      stability (10.1 +/- 0.47% vs. 11.8 +/- 0.33% damaged DNA) through the process of
      dilution, equilibration and freeze-thawing and caused a higher TAC level (81 +/-
      3.3% vs. 63 +/- 3.2 umol/L) after freez-thawing compared to the control group.
      Adding 0.576 and 1.152 mg/L zinc sulphate, however, was deleterious to the sperm
      and significantly reduced the studied sperm parameters. CONCLUSION: Adding 0.288
      mg/L zinc sulphate to the extender, compared to the control group, gives a better
      sperm preservation upon freezing processes which in turn, may results in higher
      semen fertility. But, addition of higher zinc sulphate concentrations (0.576 and
      1.152 mg/L) are detrimental to buffalo spermatozoa.

PMID- 25379164
TI  - Early pregnancy loss following laparoscopic management of ovarian abscess
      secondary to oocyte retrieval.
AB  - Severe pelvic infections following ultrasound-guided transvaginal oocyte
      retrieval (TVOR) are rare but challenging. Ovarian abscess formation is one of
      the consequences and management of such cases as highly debated in pregnant
      patients. In this case report, an early fetal loss following laparoscopic
      management of ovarian abscess is described and possible etiologies are discussed.

PMID- 25379163
TI  - Expression of RFamide-Related Peptide-3 (RFRP-3) mRNA in Dorsomedial Hypothalamic
      Nucleus and KiSS-1 mRNA in Arcuate Nucleus of Rat during Pregnancy.
AB  - BACKGROUND: RFamide-related peptide-3 (RFRP-3) and kisspeptin (KiSS-1) are known
      to respectively inhibit and stimulate gonadotropin releasing hormone (GnRH) and
      lute- inizing hormone (LH) secretion in rat. The aim of the present study was to
      evaluate the relative mRNA expression of RFRP-3 and KiSS-1 in the hypothalamus of
      pregnant rats. MATERIALS AND METHODS: In a randomized controlled experimental
      study, the exact preg- nancy day of 18 Sprague-Dawley rats were confirmed using
      the vaginal smear method and were equally assigned to three groups of days 7, 14
      and 21 of pregnancy. Four non- pregnant female rats were ovariectomized and
      assigned as the control group. All rats were decapitated, and the dorsomedial
      hypothalamic nucleus (DMH) and the arcuate nucleus (ARC) for detection of KiSS-1
      mRNA were separated from their hypothalamus to detect RFRP-3 and KiSS-1 mRNA
      respectively. Then, their relative expressions were compared between control and
      pregnant groups using real-time polymerase chain reac- tion (PCR). RESULTS: The
      relative expression of RFRP-3 mRNA in DMH did not change significantly during
      pregnancy (p>0.01). However, the relative expression of KiSS-1 mRNA in ARC was at
      its highest in day 7 of pregnancy and decreased until day 21 of pregnancy
      (p<0.01). CONCLUSION: Decrease in GnRH and LH secretion during the pregnancy of
      rat may be controlled by constant expression of RFRP-3 mRNA and reduced
      expression of KiSS-1 mRNA in hypothalamus.

PMID- 25379165
TI  - Placenta percreta resulting in incomplete spontaneous abortion in first
      trimester.
AB  - Placenta percreta is a rare complication potentially fatal to fetus and the
      mother. We present here a 41-year-old female patient who underwent curettage for
      incomplete abortion at 6(th) week of pregnancy. She had persistent vaginal
      bleeding for 2 months after the curettage, for which she was treated with
      hysterectomy. Preoperative ultrasonography and magnetic resonance imaging (MRI)
      made the diagnosis of placenta percreta. Postoperative pathological examination
      confirmed this diagnosis. 

PMID- 25379166
TI  - Late-stage [18F]Fluorination: New Solutions to Old Problems.
AB  - The last 2-3 years have seen numerous relationships develop between
      organometallic chemists, fluorine chemists and PET Centers around the world.
      These collaborations have led to the development of many new strategies for the
      late-stage introduction of fluorine-18 into complex bioactive molecules. In this
      perspective we highlight recent developments and key milestones since 2011.

PMID- 25379167
TI  - Illuminating HIV gp120-Ligand Recognition through Computationally-Driven
      Optimization of Antibody-Recruiting Molecules.
AB  - Here we report on the structure-based optimization of antibody-recruiting
      molecules targeting HIV gp120 (ARM-H). These studies have leveraged a combination
      of medicinal chemistry, biochemical and cellular assay analysis, and computation.
      Our findings have afforded an optimized analog of ARM-H, which is ~1000 fold more
      potent in gp120-binding and MT-2 antiviral assays than our previously reported
      derivative. Furthermore, computational analysis, taken together with experimental
      data, provides evidence that azaindole- and indole-based attachment inhibitors
      bind gp120 at an accessory hydrophobic pocket beneath the CD4-binding site and
      can also adopt multiple unique binding modes in interacting with gp120. These
      results are likely to prove highly enabling in the development of novel HIV
      attachment inhibitors, and more broadly, they suggest novel applications for ARMs
      as probes of conformationally flexible systems.

PMID- 25379168
TI  - Semi-automated literature mining to identify putative biomarkers of disease from
      multiple biofluids.
AB  - BACKGROUND: Computational methods for mining of biomedical literature can be
      useful in augmenting manual searches of the literature using keywords for disease
      specific biomarker discovery from biofluids. In this work, we develop and apply a
      semi-automated literature mining method to mine abstracts obtained from PubMed to
      discover putative biomarkers of breast and lung cancers in specific biofluids.
      METHODOLOGY: A positive set of abstracts was defined by the terms 'breast cancer'
      and 'lung cancer' in conjunction with 14 separate 'biofluids' (bile, blood,
      breastmilk, cerebrospinal fluid, mucus, plasma, saliva, semen, serum, synovial
      fluid, stool, sweat, tears, and urine), while a negative set of abstracts was
      defined by the terms '(biofluid) NOT breast cancer' or '(biofluid) NOT lung
      cancer.' More than 5.3 million total abstracts were obtained from PubMed and
      examined for biomarker-disease-biofluid associations (34,296 positive and
      2,653,396 negative for breast cancer; 28,355 positive and 2,595,034 negative for
      lung cancer). Biological entities such as genes and proteins were tagged using
      ABNER, and processed using Python scripts to produce a list of putative
      biomarkers. Z-scores were calculated, ranked, and used to determine significance
      of putative biomarkers found. Manual verification of relevant abstracts was
      performed to assess our method's performance. RESULTS: Biofluid-specific markers
      were identified from the literature, assigned relevance scores based on frequency
      of occurrence, and validated using known biomarker lists and/or databases for
      lung and breast cancer [NCBI's On-line Mendelian Inheritance in Man (OMIM),
      Cancer Gene annotation server for cancer genomics (CAGE), NCBI's Genes & Disease,
      NCI's Early Detection Research Network (EDRN), and others]. The specificity of
      each marker for a given biofluid was calculated, and the performance of our semi
      automated literature mining method assessed for breast and lung cancer.
      CONCLUSIONS: We developed a semi-automated process for determining a list of
      putative biomarkers for breast and lung cancer. New knowledge is presented in the
      form of biomarker lists; ranked, newly discovered biomarker-disease-biofluid
      relationships; and biomarker specificity across biofluids.

PMID- 25379170
TI  - Reducing the burden of tobacco: what's the endgame?
AB  - Tobacco use causes a tremendous amount of morbidity and mortality globally, with
      a staggering level of financial costs. In many countries, public health
      interventions have been able to reduce the prevalence of smoking and the
      associated burden. However, despite these successes, there is still much work
      left to be done. This commentary argues that the tobacco control interventions
      recommended by the World Health Organization are necessary but not sufficient to
      adequately address the consequences of tobacco use. 

PMID- 25379169
TI  - Retrospective study of the incidence of unstable and shock patients presenting to
      the emergency room.
AB  - BACKGROUND: Over a period of three decades, medical personnel working in our
      emergency room observed that fewer severe cases presented to the emergency
      department. The objective of this study is to assess whether a genuine change in
      the presentation rates of clinically unstable non-trauma patients to the
      emergency room indeed exists. METHODS: We conducted a retrospective review of
      patients treated in the shock room. Patients' demographic data, diagnoses and
      outcomes were accessed. Populations of patients presenting to the shock room over
      a span of four seasons, in two separate periods eight years apart were compared.
      This rate was compared with the complementary bulk rate of patients presenting to
      the emergency room at the center. RESULTS: While absolute rates of emergency room
      utilization rose, the rate of unstable patients demanding urgent intensive care
      showed a clear decline. An absolute reduction of close to 50% across the
      different seasons of the examined years was found. Per patient, the proportion of
      those requiring artificial respiration and urgent hemodialysis remained uniform
      in both periods. All parameters of patient outcomes were similar in both periods
      of the study. CONCLUSION: This unexplored aspect of emergency care demonstrates a
      dramatic decline in the incidence of unstable patients. While we should continue
      to reinforce delivery of superior care, our medical educational system should
      adapt itself to compensate for the diminished exposure of our trainees to
      emergencies. Further research in this field should explore whether the trend we
      observed exists in other geographical locations and whether this parameter can be
      utilized as a quality measure of medical systems.

PMID- 25379171
TI  - Summary of the findings of the International Collaboration on Mild Traumatic
      Brain Injury Prognosis.
AB  - In 2004, the WHO Collaborating Centre for Neurotrauma, Prevention, Management and
      Rehabilitation Task Force published the first large systematic review and best
      evidence synthesis on the clinical course and prognosis for recovery after MTBI.
      Ten years later, the International Collaboration on Mild Traumatic Brain Injury
      Prognosis (ICoMP) formed to update the original WHO Task Force results. This
      summary review highlights important clinical findings from the full ICoMP results
      including the current evidence on the course and prognosis of recovery after MTBI
      in diverse patient populations (e.g., adults, athletes and children) and injury
      environments (e.g., motor vehicle collisions) as well as on the risk of long-term
      outcomes after MTBI, such as Parkinson's disease and dementia. Additional
      clinical areas of interest in MTBI are also discussed including the similarities
      between MTBI and other traumatic injuries and the risk of Second Impact Syndrome
      after sport concussion. Clinicians can use this information to help inform
      patients on the likely course of recovery after MTBI/concussion and guide better
      decision-making in the care of these patients. 

PMID- 25379172
TI  - Longitudinal relaxographic imaging of white matter hyperintensities in the
      elderly.
AB  - BACKGROUND: Incidental white matter hyperintensities (WMHs) are common findings
      on T2-weighted magnetic resonance images of the aged brain and have been
      associated with cognitive decline. While a variety of pathogenic mechanisms have
      been proposed, the origin of WMHs and the extent to which lesions in the deep and
      periventricular white matter reflect distinct etiologies remains unclear. Our aim
      was to quantify the fractional blood volume (vb) of small WMHs in vivo using a
      novel magnetic resonance imaging (MRI) approach and examine the contribution of
      blood-brain barrier disturbances to WMH formation in the deep and periventricular
      white matter. METHODS: Twenty-three elderly volunteers (aged 59-82 years)
      underwent 7 Tesla relaxographic imaging and fluid-attenuated inversion recovery
      (FLAIR) MRI. Maps of longitudinal relaxation rate constant (R1) were prepared
      before contrast reagent (CR) injection and throughout CR washout. Voxelwise
      estimates of vb were determined by fitting temporal changes in R1 values to a two
      site model that incorporates the effects of transendothelial water exchange.
      Average vb values in deep and periventricular WMHs were determined after semi
      automated segmentation of FLAIR images. Ventricular permeability was estimated
      from the change in CSF R1 values during CR washout. RESULTS: In the absence of
      CR, the total water fraction in both deep and periventricular WMHs was increased
      compared to normal appearing white matter (NAWM). The vb of deep WMHs was 1.8 +/-
      0.6 mL/100 g and was significantly reduced compared to NAWM (2.4 +/- 0.8 mL/100
      g). In contrast, the vb of periventricular WMHs was unchanged compared to NAWM,
      decreased with ventricular volume and showed a positive association with
      ventricular permeability. CONCLUSIONS: Hyperintensities in the deep WM appear to
      be driven by vascular compromise, while those in the periventricular WM are most
      likely the result of a compromised ependyma in which the small vessels remain
      relatively intact. These findings support varying contributions of blood-brain
      barrier and brain-CSF interface disturbances in the pathophysiology of deep and
      periventricular WMHs in the aged human brain.

PMID- 25254105
TI  - False memory susceptibility is correlated with categorisation ability in humans.
AB  - Our memory is often surprisingly inaccurate, with errors ranging from
      misremembering minor details of events to generating illusory memories of entire
      episodes. The pervasiveness of such false memories generates a puzzle: in the
      face of selection pressure for accuracy of memory, how could such systematic
      failures have persisted over evolutionary time? It is possible that memory errors
      are an inevitable by-product of our adaptive memories and that semantic false
      memories are specifically connected to our ability to learn rules and concepts
      and to classify objects by category memberships. Here we test this possibility
      using a standard experimental false memory paradigm and inter-individual
      variation in verbal categorisation ability. Indeed it turns out that the error
      scores are significantly negatively correlated, with those individuals scoring
      fewer errors on the categorisation test being more susceptible to false memory
      intrusions in a free recall test. A similar trend, though not significant, was
      observed between individual categorisation ability and false memory
      susceptibility in a word recognition task. Our results therefore indicate that
      false memories, to some extent, might be a by-product of our ability to learn
      rules, categories and concepts. 

PMID- 25379174
TI  - Acute nutritional ketosis: implications for exercise performance and metabolism.
AB  - Ketone bodies acetoacetate (AcAc) and D-beta-hydroxybutyrate (betaHB) may provide
      an alternative carbon source to fuel exercise when delivered acutely in
      nutritional form. The metabolic actions of ketone bodies are based on sound
      evolutionary principles to prolong survival during caloric deprivation. By
      harnessing the potential of these metabolic actions during exercise, athletic
      performance could be influenced, providing a useful model for the application of
      ketosis in therapeutic conditions. This article examines the energetic
      implications of ketone body utilisation with particular reference to exercise
      metabolism and substrate energetics. 

PMID- 25379175
TI  - miRNA Temporal Analyzer (mirnaTA): a bioinformatics tool for identifying
      differentially expressed microRNAs in temporal studies using normal quantile
      transformation.
AB  - BACKGROUND: Understanding the biological roles of microRNAs (miRNAs) is a an
      active area of research that has produced a surge of publications in PubMed,
      particularly in cancer research. Along with this increasing interest, many open
      source bioinformatics tools to identify existing and/or discover novel miRNAs in
      next-generation sequencing (NGS) reads become available. While miRNA
      identification and discovery tools are significantly improved, the development of
      miRNA differential expression analysis tools, especially in temporal studies,
      remains substantially challenging. Further, the installation of currently
      available software is non-trivial and steps of testing with example datasets,
      trying with one's own dataset, and interpreting the results require notable
      expertise and time. Subsequently, there is a strong need for a tool that allows
      scientists to normalize raw data, perform statistical analyses, and provide
      intuitive results without having to invest significant efforts. FINDINGS: We have
      developed miRNA Temporal Analyzer (mirnaTA), a bioinformatics package to identify
      differentially expressed miRNAs in temporal studies. mirnaTA is written in Perl
      and R (Version 2.13.0 or later) and can be run across multiple platforms, such as
      Linux, Mac and Windows. In the current version, mirnaTA requires users to provide
      a simple, tab-delimited, matrix file containing miRNA name and count data from a
      minimum of two to a maximum of 20 time points and three replicates. To
      recalibrate data and remove technical variability, raw data is normalized using
      Normal Quantile Transformation (NQT), and linear regression model is used to
      locate any miRNAs which are differentially expressed in a linear pattern.
      Subsequently, remaining miRNAs which do not fit a linear model are further
      analyzed in two different non-linear methods 1) cumulative distribution function
      (CDF) or 2) analysis of variances (ANOVA). After both linear and non-linear
      analyses are completed, statistically significant miRNAs (P < 0.05) are plotted
      as heat maps using hierarchical cluster analysis and Euclidean distance matrix
      computation methods. CONCLUSIONS: mirnaTA is an open-source, bioinformatics tool
      to aid scientists in identifying differentially expressed miRNAs which could be
      further mined for biological significance. It is expected to provide researchers
      with a means of interpreting raw data to statistical summaries in a fast and
      intuitive manner.

PMID- 25379177
TI  - Congenital thyroid hemiagenesis with multinodular goiter.
AB  - Thyroid hemiagenesis is a rare form of thyroid dysgenesis characterized by an
      absence of half of the thyroid gland. Developmental hemi-thyroid anomalies can
      result from either an abnormal descent or an agenesis of one lobe of the thyroid
      gland. We report a case of a 40-year-old woman with history of a longstanding
      gradually progressive thyroid swelling without any complication. An
      ultrasonographic examination diagnosed the absence of the left thyroid lobe and
      enlargement of the right lobe, which was confirmed on a computed tomography (CT)
      angiogram and a radionuclide scan of the neck. A cytological examination showed
      nodular goiter with cystic degeneration. Right subtotal thyroidectomy was
      performed and histopathological examination confirmed adenomatous goiter with
      degenerative changes. We report the rarity of the condition and emphasize the
      role of a comprehensive radiological, cytological, and radionuclide algorithm for
      an accurate preoperative diagnosis and subsequent management. 

PMID- 25379176
TI  - Hydrogel scaffolds as in vitro models to study fibroblast activation in wound
      healing and disease.
AB  - Wound healing results from complex signaling between cells and their environment
      in response to injury. Fibroblasts residing within the extracellular matrix (ECM)
      of various connective tissues are critical for matrix synthesis and repair. Upon
      injury or chronic insult, these cells activate into wound-healing cells, called
      myofibroblasts, and repair the damaged tissue through enzyme and protein
      secretion. However, misregulation and persistence of myofibroblasts can lead to
      uncontrolled accumulation of matrix proteins, tissue stiffening, and ultimately
      disease. Extracellular cues are important regulators of fibroblast activation and
      have been implicated in their persistence. Hydrogel-based culture models have
      emerged as useful tools to examine fibroblast response to ECM cues presented
      during these complex processes. In this Mini-Review, we will provide an overview
      of these model systems, which are built upon naturally-derived or synthetic
      materials, and mimic relevant biophysical and biochemical properties of the
      native ECM with different levels of control. Additionally, we will discuss the
      application of these hydrogel-based systems for the examination of fibroblast
      function and fate, including adhesion, migration, and activation, as well as
      approaches for mimicking both static and temporal aspects of extracellular
      environments. Specifically, we will highlight hydrogels that have been used to
      investigate the effects of matrix rigidity, protein binding, and cytokine
      signaling on fibroblast activation. Last, we will describe future directions for
      the design of hydrogels to develop improved synthetic models that mimic the
      complex extracellular environment.

PMID- 25379178
TI  - CT diagnosis of a post-embolization ischemic diverticulitis of Meckel.
AB  - A 23-year-old man presented with hypovolemic shock due to a lower
      gastrointestinal bleeding. Radiological and endoscopic investigation did not
      reveal the bleeding site. Emergency visceral angiography showed contrast
      extravasation at a right-sided branch of the superior mesenteric artery (SMA).
      Embolization of the bleeding point was performed, resulting in bleeding
      cessation. One week later, the patient presented with a new episode of moderate
      anal blood loss associated with diffuse abdominal pain. Computed tomography (CT)
      revealed an ischemic small bowel diverticulum that was treated by a
      laparoscopically-assisted segmental small bowel resection. Intraoperative and
      pathologic analysis confirmed a post-embolization ischemic diverticulitis of
      Meckel. 

PMID- 25379180
TI  - Patient reported experiences of CT guided lung biopsy: a prospective cohort
      study.
AB  - BACKGROUND: CT guided lung biopsy is a commonly performed procedure to obtain
      tissue for a histological diagnosis in cases of suspected lung cancer. METHODS:
      This is a prospective cohort study to obtain information directly from patients
      about their experiences of the biopsy procedure, thus obtaining a more accurate
      picture of complications compared with previously performed retrospective
      reviews. Patients participated in a post-procedure telephone interview and
      information was gathered about any procedural complications and personal
      experiences. We also compared the patient reported complications with those
      obtained from a retrospective review of hospital databases, analogous to
      previously performed retrospective studies. RESULTS: In our patient group,
      reported procedural complication rates were 10% pneumothorax rate (4% requiring a
      chest drain) and 10% haemoptysis. Post-procedural pain and shortness of breath
      showed positive correlation, with one patient experiencing prolonged pain. No
      statistical difference was found between the patient reported complication rates
      and those obtained from retrospective review of the hospital database.
      CONCLUSIONS: Our study demonstrates CT guided lung biopsy is a safe procedure and
      is generally well tolerated. Some patients may experience significant and lasting
      pain and therefore should be counselled about this pre-procedure.

PMID- 25379179
TI  - Metabolic and transcriptional profiling reveals pyruvate dehydrogenase kinase 4
      as a mediator of epithelial-mesenchymal transition and drug resistance in tumor
      cells.
AB  - BACKGROUND: Accumulating preclinical and clinical evidence implicates epithelial
      mesenchymal transition (EMT) in acquired resistance to anticancer drugs; however,
      mechanisms by which the mesenchymal state determines drug resistance remain
      unknown. RESULTS: To explore a potential role for altered cellular metabolism in
      EMT and associated drug resistance, we analyzed the metabolome and transcriptome
      of three lung cancer cell lines that were rendered drug resistant following
      experimental induction of EMT. This analysis revealed evidence of metabolic
      rewiring during EMT that diverts glucose to the TCA cycle. Such rewiring was at
      least partially mediated by the reduced expression of pyruvate dehydrogenase
      kinase 4 (PDK4), which serves as a gatekeeper of the TCA cycle by inactivating
      pyruvate dehydrogenase (PDH). Overexpression of PDK4 partially blocked TGFbeta
      induced EMT; conversely, PDK4 inhibition via RNAi-mediated knockdown was
      sufficient to drive EMT and promoted erlotinib resistance in EGFR mutant lung
      cancer cells. We identified a novel interaction between PDK4 and apoptosis
      inducing factor (AIF), an inner mitochondrial protein that appears to play a role
      in mediating this resistance. In addition, analysis of human tumor samples
      revealed PDK4-low as a predictor of poor prognosis in lung cancer and that PDK4
      expression is dramatically downregulated in most tumor types. CONCLUSIONS:
      Together, these findings implicate PDK4 as a critical metabolic regulator of EMT
      and associated drug resistance.

PMID- 25379181
TI  - Meta analysis on the efficacy of pharmacotherapy versus placebo on anorexia
      nervosa.
AB  - BACKGROUND: Anorexia Nervosa (AN) has a devastating impact on the psychological
      and physical well being of affected individuals. There is an extensive body of
      literature on interventions in AN, however more studies are needed to establish
      which form of pharmacotherapy is effective. The few meta-analyses that have been
      done are based on one type of medication only. This article is the first to
      present data on three different, most commonly used, forms of pharmacotherapy.
      The primary objective of this meta-analysis was to create an overview and to
      determine the efficacy of three forms of pharmacotherapy (antidepressants,
      antipsychotics, hormonal therapy) compared to treatment with placebo in patients
      with AN. METHOD: A systematic literature search was performed to identify all
      randomized controlled intervention trials investigating the effectiveness of
      pharmacotherapy for AN within the following databases: PubMed, PsycINFO, Embase
      and Cochrane Library. In addition, 32 relevant reviews and meta-analyses were
      screened for additional intervention studies. A meta-analysis was performed on a
      total of 18 included studies (N = 869). Efficacy was measured in terms of weight
      gain or weight restoration. RESULTS: The pooled effect sizes indicating the
      difference between antidepressants and placebo, and between antipsychotics and
      placebo on weight were not significant. Because of the small sample size no meta
      regression and subgroup analyses could be conducted. The pooled effect size
      indicating the difference between hormonal therapy and the placebo condition on
      weight (all weight measures) at post-treatment was 0.42 (95% CI: 0.11 ~ 0.73),
      which was significant. For hormonal therapy heterogeneity was high (I(2) =
      64.70). No evidence for publication bias was found. Meta-regression analyses of
      the weeks of medication treatment (slope = -0.008) yielded a significant effect
      (p = 0.04). CONCLUSIONS: In this study we found that hormonal therapy has a
      significantly larger effect on weight compared to placebo in the treatment of AN.
      However for these analyses heterogeneity was high, which means that these results
      have to be regarded with caution. We found that anti-depressants and
      antipsychotics had no significant effect on weight compared to placebo in the
      treatment of AN, although the power to detect significant effects was too low.

PMID- 25379182
TI  - Primary hyperparathyroidism due to atypical vertically long cystic adenoma.
AB  - Parathyroid cystic adenomas are often misdiagnosed as thyroid cysts and routine
      preoperative diagnostic tools, such as ultrasonography (US) or 99m technetium
      sestamibi (99mTc-MIBI) scans, cannot clearly distinguish between these entities.
      We present a 67-year-old hypercalcemic woman with a cervical cystic lesion who
      had negative sestamibi scan results. Her laboratory data indicated primary
      hyperparathyroidism (serum calcium concentration 14.0 mg/dl, phosphate
      concentration 2.3 mg/dl, and intact parathyroid hormone (PTH) concentration 239
      pg/ml). The cervical US and computed tomography scans revealed a large and
      vertically long cystic mass (12*11*54 mm). A mass was located from the upper end
      of the left thyroid lobe to the submandibular region and was not clearly
      distinguishable from the thyroid. For preoperative definitive diagnosis, we
      carried out a parathyroid fine-needle aspiration (FNA) and PTH assay (PTH-FNA) of
      liquid aspirated from the cyst. The intact PTH-FNA concentration was 1.28*10(6)
      pg/ml, and the patient was diagnosed with primary hyperparathyroidism due to a
      cystic mass. She underwent a left upper parathyroidectomy and her serum calcium
      and intact PTH concentration immediately decreased to normal levels. This report
      describes the usefulness of PTH-FNA for localizing and differentiating an
      atypical functional parathyroid lesion from nonfunctional tissue in primary
      hyperparathyroidism. LEARNING POINTS: Cystic parathyroid lesions, even in the
      case of elevated PTH levels, can produce negative results in 99mTc-MIBI
      scans.Preoperative diagnosis of parathyroid cysts detectable on US is possible by
      parathyroid FNA and PTH assay (PTH-FNA) of liquid aspirated from the cyst, if
      malignancy is not suspected. PTH-FNA could be helpful in the differential
      diagnosis of an equivocal cervical tumor.

PMID- 25379183
TI  - Comparative assessment of medicine procurement prices in the United Nations
      Relief and Works Agency for Palestine Refugees in the Near East (UNRWA).
AB  - OBJECTIVES: The United Nations Relief and Works Agency for Palestine Refugees in
      the Near East (UNRWA), the main primary healthcare provider for 4.9 million
      Palestinian refugees, spent USD18.3 million on essential medicines dispensed free
      of-charge through clinics in five areas of operation ('fields'): Gaza, Jordan,
      Lebanon, Syria, and the West Bank (2010). Faced with budget contraints and an
      increasing demand for medicines to treat chronic conditions, the objective of our
      study was to assess UNRWA's medicine procurement prices to see if savings could
      be possible. METHODS: In July 2011, data was collected from UNRWA headquarters in
      Jordan. Price analyses focused on the top 80 medicines by value, accounting for
      93% of pharmaceutical expenditure from the General Fund, with comparisons to
      international, regional and national references. Prices were also compared for
      the few medicines procured both through UNRWA's central tender (centrally) and by
      the fields directly (locally). RESULTS: Central procurement prices did not differ
      markedly from reference prices: median ratios of UNRWA prices to Management
      Sciences for Health's International Drug Price Indicator Guide, Jordan's Joint
      Procurement Department, Gulf Cooperation Council, and IDA Foundation bulk packs
      were 0.99, 1.00, 0.98 and 1.12 respectively. Applying the lowest comparator price
      to five comparatively higher priced medicines would yield savings of USD1.4
      million. Local procurements were generally less cost-effective than central
      tender procurement, with notable differences across fields and medicines.
      CONCLUSIONS: Overall, UNRWA's procurement prices were competitive despite the
      relatively small quantities procured. Regular monitoring of procurement prices
      and quantities is needed in order to make informed decisions. Our evaluation also
      underscores the heavy burden of antidiabetic medicines and antimicrobials on
      UNRWA procurement expenditure.

PMID- 25379184
TI  - Removal of amoxicillin from wastewater by self-made Polyethersulfone membrane
      using nanofiltration.
AB  - The present study investigated the performance of a self-made nanofiltration (NF)
      membrane for the removal of antibiotics from wastewater under changing operating
      conditions such as pH, initial feed concentration, operating pressure, and
      temperature. Amoxicillin (AMX) was used as one of the commonly prescribed
      antibiotics. A self-made NF membrane containing Polyethersulfone (PES), and
      Polyvinylpyrrolidone (PVP) was modified with Polyethylene glycol hexadecyl ether
      (Brij(r)58) surfactant. The self-made membrane was characterized by water contact
      angle, zeta potential, ATR-FTIR spectroscopy, and scanning electronic microscope
      (SEM). The obtained results showed that the AMX rejection and permeation flux by
      the self-made membrane varied from 56.49% to 99.09% and from 15.14 L/m(2)h to
      110.29 L/m(2)h, respectively. The AMX rejection decreased at a higher level of
      initial feed concentration while other operating parameters such as pH, operating
      pressure, and temperature had a negligible effect on the removal of AMX from
      wastewater by the self-made NF membrane. The highest removal rate was achieved
      under conditions of pH 9.0, a temperature of 298 K, an operating pressure of 2
      MPa, and an initial feed concentration of 20 ppm. According to the research
      findings, the self-made NF membrane is recommended for the removal of AMX to a
      considerable extent at low initial feed concentrations. 

PMID- 25379185
TI  - The use of the GIS Kriging technique to determine the spatial changes of natural
      radionuclide concentrations in soil and forest cover.
AB  - BACKGROUND: The distribution of radionuclides occurring naturally in the earth
      depends on bedrock characteristics. Therefore, the spatial distribution of
      radionuclides is not uniform. Consequently, radionuclide information is vitally
      important in determining and monitoring the spatial variation of the radionuclide
      concentrations that are over the limits for the sustainable environment and human
      health. METHODS: This research was carried out using GIS methods and
      geostatistical analysis as Kriging techniques to reveal the spatial variation of
      the 226Ra, 232Th and 40 K concentrations of natural radionuclides in the Coruh
      and Aras Basin. The spatial variations of the detected radionuclides were
      correlated with soil groups and forest cover. RESULTS: In the study area, 43.17%
      of the concentration of 40 K, 26.67% of the concentration of 226Ra and 28.16% of
      the 232Th concentration was determined to be over the average limits.
      Concentrations of radionuclides that are over the average limits have been found
      to be on basalt and chestnut soils. Brown and reddish brown soils have a low
      concentration of the spatial distribution of the radionuclides. Statistically
      positive correlations were detected (0.865 **) between the 226Ra and 232Th. In
      addition, a positive relationship between forest cover and 226Ra and a negative
      relationship between 232Th and 40 K were identified. CONCLUSIONS: Excessive
      exposure to radiation may cause cancer and hereditary diseases. Ecological
      environments include the soil and the plants. Hence, the periodical monitoring of
      the spatial variation in concentrations of radionuclides is very important for
      the health of future generations.

PMID- 25379186
TI  - Wastewater treatment using integrated anaerobic baffled reactor and Bio-rack
      wetland planted with Phragmites sp. and Typha sp.
AB  - The purpose of this study is to examine the potential use of anaerobic baffled
      reactor (ABR) followed by Bio-rack wetland planted with Phragmites sp. and Typha
      sp. for treating domestic wastewater generated by small communities (751 mg
      COD/L, 500 SCOD mg/L, 348 mg BOD5/L). Two parallel laboratory-scale models showed
      that the process planted with Phragmites sp. and Typha sp. are capable of
      removing COD by 87% & 86%, SCOD by 90% & 88%, BOD5 by 93% & 92%, TSS by 88% &
      86%, TN by 79% & 77%, PO4-P by 21% & 14% at an overall HRT of 21 (843 g
      COD/m(3)/day & 392 g BOD5/m(3)/day) and 27 (622 g COD/m(3)/day & 302 g
      BOD5/m(3)/day) hours, respectively. Microbial analysis indicated a high reduction
      in the MPN of total coliform and TVC as high as 99% at the outlet end of the
      processes. The vegetated system using Phragmites sp. showed significantly greater
      (p <0.05) pollutant removal efficiencies due to its extensive root and mass
      growth rate (p <0.05) of the plant compared to Typha sp. The Phragmites sp.
      indicated a higher relative growth rate (3.92%) than Typha sp. (0.90%).
      Microorganisms immobilized on the surface of the Bio-rack media (mean TVC: 2.33 *
      10(7) cfu/cm(2)) were isolated, identified and observed using scanning electron
      microscopy (SEM). This study illustrated that the present integrated processes
      could be an ideal approach for promoting a sustainable decentralization, however,
      Phragmites sp. would be more efficient rather than Typha sp. 

PMID- 25379187
TI  - Blood lead levels of Korean lead workers in 2003-2011.
AB  - OBJECTIVES: This study aimed to document the trend in blood lead levels in Korean
      lead workers from 2003 until 2011 and blood lead levels within each of the main
      industries. METHODS: Nine years (2003-2011) of blood lead level data measured
      during a special health examination of Korean lead workers and collected by the
      Korea Occupational Safety and Health Agency were analyzed. Blood lead levels were
      determined by year, and a geometric mean (GM) was calculated for each industry
      division. RESULTS: The overall GM blood lead level for all years combined (n =
      365,331) was 4.35 MUg/dL. The GM blood lead level decreased from 5.89 MUg/dL in
      2003 to 3.53 MUg/dL in 2011. The proportion of the results >=30 MUg/dL decreased
      from 4.3% in 2003 to 0.8% in 2011. In the "Manufacture of Electrical Equipment"
      division, the GM blood lead level was 7.80 MUg/dL, which was the highest among
      the industry divisions. The GM blood lead levels were 7.35 MUg/dL and 6.77 MUg/dL
      in the "Manufacturers of Rubber and Plastic Products" and the "Manufacture of
      Basic Metal Products" division, respectively. CONCLUSIONS: The blood lead levels
      in Korean lead workers decreased from 2003 to 2011 and were similar to those in
      the US and UK. Moreover, workers in industries conventionally considered to have
      a high risk of lead exposure also tended to have relatively high blood lead
      levels compared to those in other industries.

PMID- 25379188
TI  - Role of early repeated renal biopsies in lupus nephritis.
AB  - OBJECTIVES: A renal biopsy is generally recommended for diagnosis and is
      necessary for classification of lupus nephritis (LN), but second biopsies after
      immunosuppressive therapy are seldom a routine procedure. We investigated how
      repeat biopsies contribute to the evaluation of treatment response and long-term
      outcome in LN. METHODS: Sixty-seven patients with active LN were included. Renal
      biopsies were performed at diagnosis and after standard induction
      immunosuppressive therapy in all patients (median 8 months), regardless of
      clinical outcome. Biopsies were evaluated according to the International Society
      of Nephrology/Renal Pathology Society classification. Clinical response was
      defined as complete (CR), partial (PR) or non-response (NR) according to recent
      definitions. Histological response (HR) was defined as Class I, II or III/IV-C on
      repeat biopsies. Long-term renal outcome was determined in 55 patients after a
      median of 10 years. RESULTS: CR was demonstrated in 25%, PR in 27% and NR in 48%
      of patients. HR was shown in 42% and histopathological non-response (HNR) in 58%
      of patients. Twenty-nine per cent of CR and 61% of patients with PR had active
      lesions on repeat biopsies, that is, were HNR. Poor long-term renal outcome was
      associated with high chronicity index at repeated biopsies, but not with clinical
      or histological response. CONCLUSIONS: Despite apparent clinical response to
      immunosuppressive therapy, repeated biopsies revealed persisting active nephritis
      in almost half of the patients, thus providing additional information to clinical
      response criteria. Repeated renal biopsies may be a tool to improve the
      evaluation of treatment response in LN.

PMID- 25379189
TI  - Incidence and prevalence of lupus in Buenos Aires, Argentina: a 11-year health
      management organisation-based study.
AB  - OBJECTIVES: Studies regarding the epidemiology of systemic lupus erythematosus
      (SLE) are lacking in Argentina. Our purpose was to estimate the incidence and
      prevalence of SLE in a university hospital-based health management organisation
      in Buenos Aires (HIMCP). METHODS: For incidence calculation, the population at
      risk included all adult members of the HIMCP, with continuous affiliation for at
      least 1 year from January 1998 to January 2009. Each person was followed until
      he/she voluntarily left the HIMCP, death or finalisation of the study. Multiple
      methods for case finding were used to ensure complete ascertainment: (a) patients
      with problem SLE, undifferentiated autoimmune disease or mixed connective tissue
      disease in the Computer-based Patient Record System, (b) patients with positive
      antinuclear antibody test, anti-Sm antibodies and/or anti-dsDNA antibodies in the
      laboratory database and (c) patients who consumed hydroxichloroquine,
      chloroquine, azathioprine, cyclophosphamide, mycophenolate, cyclosporine or
      rituximab, from the administrative HIMCP drugs database. Medical records of all
      patients found were reviewed, and only patients fulfilling ACR criteria for SLE
      were included. Global and gender incidence rate (IR) was calculated. Prevalence
      was estimated on 1 January 2009, and the denominator population was the number of
      active members >18 years at that date (n=127 959). RESULTS: In the study period,
      68 patients developed SLE. The observed IR (per 100 000 person-years, (CI 95%))
      was 6.3 (4.9 to 7.7) for total population; 8.9 (CI 6.6 to 11.2) for women and 2.6
      (1.2 to 3.9) for men. On 1 January 2009, 75 prevalent cases were identified.
      Prevalence rates (cases per 100 000 habitants, (CI 95%)) were 58.6 (46.1 to 73.5)
      for total population; 83.2 (63.9 to 106.4) for women and 23 (CI 11.9 to 40.1) for
      men. CONCLUSIONS: SLE incidence and prevalence rates in Argentina are in
      agreement with those of other studies from different parts of the world.

PMID- 25379190
TI  - Exploring lifetime occupational exposure and SLE flare: a patient-focussed pilot
      study.
AB  - INTRODUCTION: Environmental effectors, such as ultraviolet radiation exposure,
      infection and stress, have been established as having a role in exacerbating
      lupus symptoms. However, unpredictable patterns of flare events still remain a
      mystery. Occupational effectors have also been suggested as having a contributing
      role; however, they are not widely researched. In this paper we report a pilot
      study designed to generate focus areas for future research regarding occupational
      exposures and systemic lupus erythematosus (SLE). METHODS: The study explored
      potential links between exposures and the occurrence of patient-reported flare
      events in 80 Australian women with SLE (American College of Rheumatology (ACR)
      criteria classified). Specifically, the study assessed the hypothesis that
      occupational exposure is associated with significant changes in the likelihood of
      lupus flares. Lifetime employment history was analysed with the Finnish Job
      Exposure Matrix (FINJEM), 40 different semiquantified exposure class estimates
      for a wide number of occupations based on probability of exposure (p>=5%=exposed)
      were analysed with the construction of negative binomial regression models to
      test relationships between occupational agents and flare days. A backward
      stepwise elimination was used to generate a parsimonious model. RESULTS:
      Significant associations were noted for exposure classes of manual handling
      burden, (p=0.02, incidence rate ratio (IRR) 1.01), Iron (p=0.00, IRR 1.37), wood
      dust (p=0.00, IRR 3.34) and asbestos (p=0.03, IRR 2.48). CONCLUSION: Exposure
      assessment results indicated that occupations, such as nursing, with a high
      manual handling burden, posed increased risk to patients with SLE, however, the
      greatest risk was associated with wood dust and iron exposure with teachers and
      specialist labourers.

PMID- 25379193
TI  - Lupus Science and Medicine: the Editors present highlights for the bedside and
      for the bench in the inaugural issue.

PMID- 25379191
TI  - Adverse pregnancy outcomes and subsequent risk of cardiovascular disease in women
      with systemic lupus erythematosus.
AB  - BACKGROUND/OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at
      increased risk for adverse pregnancy outcomes and cardiovascular disease (CVD).
      The objective of this exploratory study was to investigate the association
      between a history of adverse pregnancy outcomes and subsequent risk of
      subclinical CVD assessed by imaging studies and verified clinical CVD events in
      129 women with SLE. METHODS: The occurrence of adverse pregnancy outcomes,
      specifically pre-eclampsia, preterm birth and low birth weight was ascertained by
      questionnaire. Subclinical CVD was assessed by coronary artery calcium (CAC) as
      measured by electron beam CT and carotid plaque measured by B mode ultrasound.
      Clinical CVD events were verified by medical record review. Logistic regression
      was used to estimate the association of pregnancy complications with occurrence
      of subclinical CVD and clinical CVD with a priori adjustment for age, which is
      associated with CVD and SLE disease duration as a measure of SLE disease burden.
      RESULTS: Fifty-six women reported at least one pregnancy complication while 73
      had none. Twenty-six women had at least one pregnancy complicated by pre
      eclampsia and were more likely to have a CAC score greater than or equal to 10
      (adjusted OR=3.7; 95% CI 1.2 to 11.9), but the presence of plaque was not
      associated with this pregnancy complication, OR=1.1, (95% CI 0.4 to 2.8). Low
      birth weight and preterm birth were not associated with CAC or plaque.
      CONCLUSIONS: Patients with SLE with a history of pre-eclampsia had a higher rate
      of subclinical CVD as measured by CAC score. Future studies are needed to confirm
      the relationship between adverse pregnancy outcomes and subsequent subclinical
      CVD and clinical CVD events.

PMID- 25379194
TI  - Increased usage of special educational services by children born to mothers with
      systemic lupus erythematosus and antiphospholipid antibodies.
AB  - INTRODUCTION: Surveys of long-term health and developmental outcomes of children
      born to mothers with systemic lupus erythematosus (SLE) have suggested an
      increase in learning disabilities among these children. We performed this
      observational study to investigate the relationship between maternal
      autoantibodies and antiphospholipid antibody syndrome (APS) in maternal lupus
      patients and neurocognitive development among their offspring. METHODS: SLE
      mothers with at least one live birth postlupus diagnosis were enrolled. Data on
      maternal medical/obstetric history and children's perinatal/medical history were
      collected by structured interview and medical record reviews. The primary outcome
      was requirement for special educational (SE) services, a proxy for developmental
      delays. Multiple logistic regression modelling was used to examine associations
      between APS and autoantibodies with SE usage, accounting for SLE disease severity
      and potential confounders. RESULTS: Data on 38 mothers and 60 offspring were
      analysed: SE service usage was reported for 15 of 60 (25%) offspring. Maternal
      APS history was significantly associated with increased use of SE services among
      offspring, including after adjustment for lupus anticoagulant (LA) positivity and
      potential confounders (OR 5.5-9.4 for delays age >=2; p<0.05). The presence of
      LA, but not other antiphospholipid antibodies, was also associated with increased
      SE services usage. CONCLUSIONS: Maternal APS and LA were independently associated
      with increased usage of special educational services among offspring of women
      with SLE.

PMID- 25379195
TI  - Challenges in understanding the role of pregnancy morbidity in cardiovascular
      risk in SLE.

PMID- 25379196
TI  - Lupus science and medicine: dialogue.

PMID- 25379192
TI  - Lower vitamin D levels are associated with higher systemic lupus erythematosus
      activity, but not predictive of disease flare-up.
AB  - OBJECTIVES: Growing evidence suggests that vitamin D plays a key role in the
      pathogenesis and progression of autoimmune diseases, including systemic lupus
      erythematosus (SLE). Recent studies have found an association between lower serum
      25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the
      relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease
      Activity Index (SLEDAI) score, and we assessed for the first time the role of
      vitamin D in predicting SLE flare-ups. METHODS: Serum 25(OH)D levels were
      measured in 170 patients with SLE who were prospectively followed up for 6 months
      (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). RESULTS:
      The mean SLEDAI score was 2.03+/-2.43 and 12.3% patients had active disease
      (SLEDAI >=6). The mean 25(OH)D level was 20.6+/-9.8 ng/mL. Deficiency (25(OH)D
      <10 ng/mL) was observed in 27 (15.9%), insufficiency (10<=25(OH)D<30) in 112
      (65.9%) and optimal vitamin D status (25(OH)D>=30) in 31 (18.2%) patients. In
      multivariate analysis, female gender (p=0.018), absence of defined
      antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004)
      were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D
      levels were associated with high SLE activity (p=0.02). Relapse-free survival
      rate was not statistically different according to the vitamin D status during the
      6-month follow-up (p=0.22). CONCLUSIONS: We found a low vitamin D status in the
      majority of patients with SLE, and a modest association between lower 25(OH)D
      levels and high disease activity. There was no association between baseline
      25(OH)D levels and relapse-free survival rate.

PMID- 25379197
TI  - Evolving from conventional video-assisted thoracoscopic lobectomy to uniportal:
      the story behind the evolution.

PMID- 25379198
TI  - The evolution of minimally invasive thoracic surgery: implications for the
      practice of uniportal thoracoscopic surgery.
AB  - The history of Minimally Invasive Surgery in the thorax is one of evolution, not
      revolution. The concept of video-assisted thoracic surgery (VATS) to greatly
      reduce the trauma of chest operations was born over two decades ago. Since then,
      it has undergone a series of step-wise modifications and improvement. The
      original practice of three access ports in a 'baseball diamond' pattern was
      modified to suit operational needs, and gradually developed into 'next
      generation' approaches, including Needlescopic and 2-port VATS. The logical,
      incremental progression has culminated in the Uniportal VATS approach which has
      stirred considerable interest within the field of Thoracic Surgery in recent
      years. This measured, evolutionary process has significant implications on how
      the surgeon should approach, master and realize the full potential of the
      Uniportal technique. This article gives a precis of the evolutionary history of
      minimally invasive thoracic surgery, and highlights the lessons it provides about
      its future. 

PMID- 25379199
TI  - The uni-portal video-assisted thoracic surgery: achievements and potentials.
AB  - Described for the first time in 2004 for performing minor lung resection, during
      the following ten years a growing scientific evidence supported the spread and
      evolution of the uni-portal video-assisted thoracic surgery (VATS). This novel
      approach, performed using a single thoracic incision, requires a change of
      perspective in relation to traditional VATS, offering on the other hand a great
      versatility for numerous surgical procedures. The present work reviews the
      literature inherent to the uni-portal VATS with the aim of highlighting the
      principles of this technique, the fields of application, the obtained results and
      the future perspectives. 

PMID- 25379200
TI  - Technical difficulties and extending the indications for VATS lobectomy.
AB  - BACKGROUND: Data on advantages of video-assisted thoracoscopic surgery (VATS)
      lobectomies has been accumulated during the last 10 years then number of
      thoracoscopic anatomic pulmonary resections rapidly increased. But still there is
      no agreement about limitations of the method. The most popular "technical
      contraindications" for VATS anatomic pulmonary resections are: dense pleural
      adhesions, incompleteness of interlobar fissure, previous chemo- or/and
      radiotherapy, perivascular or/and peribronchial fibrosis, tumor larger than 5 cm,
      chest wall involvement, centrally located tumor, severe comorbidity, advanced
      age, severe COPD and emphysema. Extending of indications for the VATS anatomic
      pulmonary resection and its influence on the immediate outcomes was investigated.
      METHODS: Ninety two consecutive cases of VATS anatomic pulmonary resection
      performed by the single surgeon from January 2012 till December 2013 at the
      Federal University Hospital #122 in Saint Petersburg, Russia were retrospectively
      analyzed. Forty three males and 49 females at the age from 21 to 87 years old
      (mean age 59+/-7.2). The most of the cases were comprised by lung cancer of I-III
      stage together with bronchiectasis and tuberculomas. Conversion rate was 3.2%
      mostly due to perivascular calcification and/or fibrosis. There were no cases of
      30-days mortality and readmission. All those patients retrospectively divided
      into two groups: with standard and extended indications for the VATS lobectomy.
      Inclusion in "extended" group was made if patients had one or more technical
      challenges among following: size of the lesion 5 cm and more; strong pleural
      adhesions and/or "bad fissure"; adjacent structures involvement; hilar or
      mediastinal lymph nodes enlargement or involvement; centrally located tumors;
      previous chemo- or chemoradiotherapy or previous thoracic surgery. RESULTS:
      According to these criteria, 45 standard (S) and 47 extended (E) patients were
      pair-matched with no statistically significant differences between the groups in
      common patients' characteristics. Postoperative comparison of "standard" and
      "expanded" groups revealed some differences in average operation time (152 vs.
      189 min), in number of resected mediastinal lymph nodes (10.2 vs. 13.1), and in
      the mean time before removal of the chest tube (3.9 vs. 5.2 days). But the blood
      loss, morbidity and the length of hospital stay were almost the same in the two
      groups. CONCLUSIONS: Extension of indications to VATS lobectomy does not
      compromise the short-term results. Incompleteness of interlobar fissures, pleural
      adhesions, preoperative chemotherapy, big size of lesion, and some cases of
      centrally located tumors are not supposed to be the contraindications for VATS
      lobectomy. Peribronchial and perivascular lymph node calcification may complicate
      and even preclude lobectomy by VATS.

PMID- 25379201
TI  - Modern impact of video assisted thoracic surgery.
AB  - With advancement in technology, experience and training over the last two
      decades, video assisted thoracic surgery (VATS) has become widely accepted and
      utilized all over the world. VATS started as a diagnostic tool in the early
      1990s, technique of VATS lobectomy evolved and became safer over the next 10-15
      years and now it is being used for more advanced and hybrid operations. VATS has
      contributed to the development of minimally invasive surgical interventions for
      other thoracic disorders like mediastinal tumors and esophageal cancer as well.
      This article looks at the advantages of VATS, technique advancements and its
      applications in other thoracic operations and its influence on the present and
      future of thoracic surgery. 

PMID- 25379202
TI  - Challenging cases: thoracoscopic lobectomy with chest wall resection and sleeve
      lobectomy-Duke experience.
AB  - Video-assisted thoracoscopic surgery (VATS) had recent advances in both equipment
      and technique so has been applied to more complex conditions in some thoracic
      surgery centers. We have adopted our VATS lobectomy experience for patients with
      chest wall invasion and endobronchial localized tumor requiring bronchial sleeve
      resection. We are describing our decision-making and surgical methods for these
      patients which we believe will be decreasing the number of contraindications for
      VATS and offering this surgical method for more patients. 

PMID- 25379203
TI  - Uniportal video assisted thoracoscopic lobectomy: going directly from open
      surgery to a single port approach.
AB  - Uniportal video-assisted thoracoscopy (VATS) has gaining a special place in the
      thoracic surgery scenario; nowadays even major pulmonary resections can be
      performed through this approach. We hereby review our initial experience with
      uniportal VAT lobectomy, performed passing directly from the open approach to a
      single port approach. We attempted 26 lobectomies through VATS with a single
      incision of about 5 cm and 22 of them were completed: eight left lower
      lobectomies, six right upper lobectomies, five left upper lobectomies and three
      right lower lobectomies. At pathological staging all but four patients were stage
      I; three patients were T2N1M0 and one had a micrometastasis in a lymph node of
      station 7 (T1N2M0-Stage IIIA) and they all underwent adjuvant chemotherapy. No
      perioperative mortality was observed. One patient had a myocardial infarction in
      the first postoperative day requiring placement of four stents and another one
      required thoracentesis after drainage removal. The mean time for drainage removal
      was 3 days and the length of hospitalization was 4.2+/-1.1. Pain as measured by
      the visual analogical scale (VAS) scale was graded as 4.9, 2.6 and 0.5 during the
      first postoperative day, at discharge and after 1 month respectively. 

PMID- 25379204
TI  - From open surgery to uniportal VATS: asturias experience.
AB  - OBJECTIVE: Uniportal video-assisted thoracic surgery (VATS) resections are of
      increasing interest in many thoracic surgery departments. This study shows our
      initial experience in uniportal VATS anatomical resections in direct transition
      from posterolateral thoracotomy. PATIENTS AND METHODS: We retrospectively
      reviewed the 82 files of patients on whom anatomical pulmonary resection via
      uniportal VATS was attempted in our department by a single surgeon experienced in
      VATS for almost all purposes except major pulmonary resections. Demographic data
      of patients, smoking habits, chronic obstructive pulmonary disease (COPD),
      presence of cardiopulmonary comorbidities, general characteristics of pulmonary
      lesions, preoperative FEV1, intraoperative findings, operative time,
      postoperative-drain-time, hospital-stay-time, successfully completed or converted
      to thoracotomy, intraoperative and postoperative complications and 30-day
      mortality were recorded. The patients were chronologically divided into two
      groups for analysis (A: operated on in the first year; B: operated on after the
      first year). We compare our results with the largest published experience in
      anatomical resections by uniportal VATS started from multiport technique and
      anterior thoracotomy in order to identify the feasibility of this transition.
      RESULTS: From January 2012 to January 2014, 82 uniportal VATS anatomical
      pulmonary resections were attempted. Of these 82 resections attempted, 74 (90.2%)
      were completely carried out. The median drain-time and hospital-stay-time were 3
      days, and 4 days for the first year of experience and 2 and 3 days for the second
      year of experience respectively. The most frequent intraoperative complication
      was bleeding in 10 (12.1%), of these 8 occurred in the first year of experience
      (group A). In 8 (9.75%) cases conversion to thoracotomy widening the incision was
      needed for different reasons, of these 6 occurred in group A. The most frequent
      minor complication was chest tube reinsertion in 12 (14.6%) patients. There were
      no major complications or mortality in the first year of experience (group A).
      Two cases of mortality in the 8(th) and 15(th) postoperative day respectively
      occurred in group B in two patients with serious comorbidities. CONCLUSIONS:
      Uniportal VATS for anatomical resections is a feasible and safe technique with
      good results even if experience is started in direct transition from open
      surgery, on condition that general recommendations for an initial VATS program
      were observed. Specific training courses with experts are also necessary. Patient
      selection is crucial. The number of procedures necessary to obtain appropriate
      experience may be similar to those reported for transition from open surgery to
      multiport technique.

PMID- 25379205
TI  - Uniportal VATS: the first German experience.
AB  - BACKGROUND: The acceptance of uniportal video-assisted thoracic surgery (VATS)
      for minor and major thoracic procedures is growing in Europe. This study presents
      the first experience with uniportal VATS in Germany. METHODS: In a retrospective
      study of prospectively collected data, 56 uniportal VATS were analyzed between
      06/2012 and 06/2014. The technique was used for diagnostic aims, pleurectomies,
      wedge resections, segmentectomies and major resections. All procedures were
      performed without rib spreading. Patients' demographic data, preoperative and
      postoperative management as well as results were analyzed. RESULTS: A total of 42
      patients (75%) were males. The mean age was 59.2+/-15 years. The uniportal VATS
      procedures included one or multiple wedge resections in 30 cases (53.6%), major
      resections in 9 cases (16.1%), anatomical segment resections in 6 cases (10.7%)
      and other indications in 11 cases (19.6%). The median operation time was 252,
      114, 88 and 73 minutes for major resections, anatomical segment resections, wedge
      resections and other indications, respectively. There were three conversions in
      two cases of major resections and in one anatomical segmentectomy. The mean chest
      tube duration was 3.4+/-2.1 days. The mean hospital stay was 8.3+/-5.3 days for
      the whole group. CONCLUSIONS: Uniportal VATS is a feasible and safe technique for
      various indications in thoracic surgery. The perioperative results are promising.
      It can be performed by thoracic surgeons experienced in the postero-lateral
      thoracotomy approach.

PMID- 25379206
TI  - Uniportal video-assisted thoracoscopic lobectomy in the animal model.
AB  - We introduce the training on uniportal video-assisted thoracoscopic (VATS)
      lobectomy in sheep. This animal model is helpful to learn the different view, the
      importance of lung exposure and the key points of the instrumentation. In this
      article we present three videos with the left upper lobectomy, the left lower
      lobectomy and the right upper lobectomy in the sheep. 

PMID- 25379207
TI  - Technique of uniportal VATS major pulmonary resections.
AB  - The surgical approach to lung resections is evolving constantly. Since the video
      assisted thoracoscopic surgery (VATS) anatomic lobectomy for lung cancer was
      described two decades ago, many units have successfully adopted this technique.
      The VATS lobectomy can be defined as the individual dissection of veins, arteries
      and bronchus, with a mediastinal lymphadenectomy, using a videothoracoscopic
      approach visualized on screen and involving 2 to 4 incisions or ports, with no
      rib spreading. However, the surgery can be performed by only one incision with
      similar outcomes. Since 2010, when the uniportal approach was introduced for
      major pulmonary resections, the technique has been spreading worldwide. This
      technique provides a direct view of the target tissue. The parallel
      instrumentation achieved during the single-port approach mimics the maneuvers
      performed during open surgery. It represents a less invasive approach than the
      multiport technique, and minimizes the compression of the intercostal nerve. As
      the surgeon's experience with the uniportal VATS lobectomy grows, more complex
      cases can be performed by using this approach, thus expanding the indications for
      single-incision thoracoscopic lobectomy. 

PMID- 25379208
TI  - Uniportal video-assisted thoracoscopic lymph node dissection.
AB  - Lymphadenectomy is an important part of lung cancer surgery. At the moment, video
      assisted thoracoscopic (VATS) is the most common approach to remove these tumors,
      when it is technically possible. With our current experience in VATS in major
      resections we have obtained a radical videothoracoscopic mediastinal
      lymphadenectomy, and single-port provides us with the best anatomic
      instrumentation and a direct view. 

PMID- 25379209
TI  - Management of complications by uniportal video-assisted thoracoscopic surgery.
AB  - Since the video-assisted thoracoscopic surgery (VATS) anatomic lobectomy for lung
      cancer was described two decades ago, many units have successfully adopted this
      technique. VATS lobectomy is a safe and effective approach for the treatment not
      only of early stage lung cancer but also for more advanced disease. It represents
      a technical challenge. As the surgeon's experience grows, more complex or
      advanced cases are approached using the VATS approach. However, as VATS lobectomy
      has been applied to more advanced cases, the rate of conversion to open
      thoracotomy has increased, particularly early in the surgeon's learning curve,
      mostly due to the occurrence of complications. The best strategy for facing
      complications of VATS lobectomy is to prevent them from happening. Avoiding
      complications is subject to an appropriate preoperative workup and patient
      selection. Planning for a VATS resection as safely as possible involves the
      consideration of the patient's characteristics and the anticipated technical
      aspects of the case. Awareness of the possibility of intraoperative complications
      of VATS lobectomy is mandatory to avoid them, and the development of management
      strategies is necessary to limit morbidity if they occur. 

PMID- 25379210
TI  - Uniportal video-assisted thoracoscopic sleeve lobectomy and other complex
      resections.
AB  - Thanks to the recent improvements in thoracoscopy, a great deal of complex lung
      resections can be performed without performing thoracotomies. During the last
      years, experience gained through video-assisted thoracoscopic techniques,
      enhancement of the surgical instruments and improvement of high definition
      cameras have been the greatest advances. The huge number of surgical videos
      posting on specialized websites, live surgery events and experimental courses has
      contributed to the rapid learning of minimally invasive surgery during the last
      years. Nowadays, complex resections, such as post chemo-radiotherapy resections,
      lobectomies with chest wall resection, bronchial and vascular sleeves are being
      performed by thoracoscopic approach in experienced centers. Additionally, surgery
      has evolved regarding the thoracoscopic surgical approach, allowing us to perform
      these difficult procedures by means of a small single incision, with excellent
      postoperative results. 

PMID- 25379211
TI  - Behavioral sciences: an international, open-access, peer reviewed journal.
AB  - On behalf of the Editorial Board and the editorial management staff of MDPI, it
      is my great pleasure to introduce this new journal Behavioral Sciences.
      Behavioral Sciences seeks to publish original research and scholarship
      contributing to our understanding of human behavior. The journal will provide a
      forum for work that furthers knowledge and stimulates research in the behavioral
      sciences. We are committed to building a diverse and methodologically rigorous
      literature of interest and benefit to behavioral and social scientists, as well
      as to clinical practitioners, educationalists, and the general public. 

PMID- 25379212
TI  - Toward a brighter future for psychology as an observation oriented science.
AB  - Serious criticisms of psychology's research practices and data analysis methods
      date back to at least the mid-1900s after the Galtonian school of thought had
      thoroughly triumphed over the Wundtian school. In the wake of Bem's (2011)
      recent, highly publicized study on psi phenomena in a prestigious journal,
      psychologists are again raising serious questions about their dominant research
      script. These concerns are echoed in the current paper, and Observation Oriented
      Modeling (OOM) is presented as an alternative approach toward data
      conceptualization and analysis for the social and life sciences. This approach is
      rooted in philosophical realism and an attitude toward data analysis centered
      around causality and common sense. Three example studies and accompanying data
      analyses are presented and discussed to demonstrate a number of OOM's advantages
      over current researcher practices. 

PMID- 25379214
TI  - Behavioral effects of upper respiratory tract illnesses: a consideration of
      possible underlying cognitive mechanisms.
AB  - Previous research has shown that both experimentally induced upper respiratory
      tract illnesses (URTIs) and naturally occurring URTIs influence mood and
      performance. The present study investigated possible cognitive mechanisms
      underlying the URTI-performance changes. Those who developed a cold (N = 47) had
      significantly faster, but less accurate, performance than those who remained
      healthy (N = 54). Illness had no effect on manipulations designed to influence
      encoding, response organisation (stimulus-response compatilibility) or response
      preparation. Similarly, there was no evidence that different components of
      working memory were impaired. Overall, the present research confirms that URTIs
      can have an effect on performance efficiency. Further research is required to
      identify the physiological and behavioral mechanisms underlying these effects. 

PMID- 25379213
TI  - Stress alters the discriminative stimulus and response rate effects of cocaine
      differentially in lewis and Fischer inbred rats.
AB  - Stress enhances the behavioral effects of cocaine, perhaps via hypothalamic
      pituitary-adrenal (HPA) axis activity. Yet, compared to Fischer 344 (F344) rats,
      Lewis rats have hyporesponsive HPA axis function and more readily acquire cocaine
      self-administration. We hypothesized that stress would differentially affect
      cocaine behaviors in these strains. The effects of three stressors on the
      discriminative stimulus and response rate effects of cocaine were investigated.
      Rats of both strains were trained to discriminate cocaine (10 mg/kg) from saline
      using a two-lever, food-reinforced (FR10) procedure. Immediately prior to
      cumulative dose (1, 3, 10 mg/kg cocaine) test sessions, rats were restrained for
      15-min, had 15-min of footshock in a distinct context, or were placed in the
      shock-paired context. Another set of F344 and Lewis rats were tested similarly
      except they received vehicle injections to test if stress substituted for
      cocaine. Most vehicle-tested rats failed to respond after stressor exposures.
      Among cocaine-tested rats, restraint stress enhanced cocaine's discriminative
      stimulus effects in F344 rats. Shock and shock-context increased response rates
      in Lewis rats. Stress-induced increases in corticosterone levels showed strain
      differences but did not correlate with behavior. These data suggest that the
      behavioral effects of cocaine can be differentially affected by stress in a
      strain-selective manner. 

PMID- 25379215
TI  - Summation by Asian Elephants (Elephas maximus).
AB  - Recent empirical evidence for complex cognition in elephants suggests that
      greater attention to comparative studies between non-human primates and other
      animals is warranted. We have previously shown that elephants possess the ability
      to judge the difference between two discrete quantities, and unlike other
      animals, their choice does not appear to be affected by distance or overall
      quantity. In this study, we investigated Asian elephants' ability to perform
      summation, as exemplified by the ability to combine four quantities into two sums
      and subsequently compare them. We presented two discrete sums (3-7) to the
      elephants by baiting two buckets; they were loaded sequentially with two discrete
      quantities (1-5 pieces) of food per bucket. All three elephants selected the
      larger grand sum significantly more often than the smaller grand sum. Moreover,
      their performance was not affected by either distance to the bait or the overall
      quantity evaluated. Studies report that the performance of other animal species
      on similar tasks declines as distance to the bait decreases and as the overall
      quantities evaluated increase. These results suggest that the numerical cognition
      of Asian elephants may be different from that of other animals, but further study
      is required to elucidate the differences precisely. 

PMID- 25379216
TI  - Physiological consequences of repeated exposures to conditioned fear.
AB  - Activation of the stress response evokes a cascade of physiological reactions
      that may be detrimental when repeated or chronic, and when triggered after
      exposure to psychological/emotional stressors. Investigation of the physiological
      mechanisms responsible for the health damaging effects requires animal paradigms
      that repeatedly evoke a response to psychological/emotional stressors. To this
      end, adult male Sprague Dawley rats were repeatedly exposed (2X per day for 20
      days) to a context that they were conditioned to fear (conditioned fear test,
      CFT). Repeated exposure to CFT produced body weight loss, adrenal hypertrophy,
      thymic involution, and basal corticosterone elevation. In vivo biotelemetry
      measures revealed that CFT evokes sympathetic nervous system driven increases in
      heart rate (HR), mean arterial pressure (MAP), and core body temperature.
      Extinction of behavioral (freezing) and physiological responses to CFT was
      prevented using minimal reinstatement footshock. MAP responses to the CFT did not
      diminish across 20 days of exposure. In contrast, HR and cardiac contractility
      responses declined by day 15, suggesting a shift toward vascular-dominated MAP (a
      pre-clinical marker of CV dysfunction). Flattened diurnal rhythms, common to
      stress-related mood/anxiety disorders, were found for most physiological
      measures. Thus, repeated CFT produces adaptations indicative of the health
      damaging effects of psychological/emotional stress. 

PMID- 25379217
TI  - Symptom persistence and memory performance in posttraumatic stress disorder: a
      gene x environment pilot stud.
AB  - The FKBP5 gene, a glucocorticoid receptor (GR)-regulating co-chaperone of stress
      proteins, is of special interest because of its role in hypothalamic-pituitary
      adrenal (HPA)-axis regulation. However, studies finding a genetic relationship
      between posttraumatic stress disorder (PTSD) and the FKBP5 gene have failed to
      distinguish between the development and persistence of PTSD, thereby limiting the
      prognostic usefulness of such a finding. The present study sought to
      longitudinally explore this question by examining the association between four
      single-nucleotide polymorphisms (SNPs) in the FKBP5 gene (rs3800373, rs9470080,
      rs1360780, and rs9296158), the persistence of PTSD (severity and diagnostic
      status), and memory performance among twenty-two treatment-seekers diagnosed with
      acute PTSD. Results showed that the four SNPs significantly interacted with
      improvement in PTSD symptoms as well as PTSD diagnostic status. Individuals
      homozygous for the dominant allele and having experienced higher levels of
      peritraumatic responses subsequently showed more memory dysfunction. The results
      of this study suggest that SNPs in the FKBP5 gene are associated with symptom
      persistence and memory dysfunction in acute PTSD. 

PMID- 25379218
TI  - Brief Treatment of Symptoms of Post-Traumatic Stress Disorder (PTSD) by Use of
      Accelerated Resolution Therapy (ART((r))).
AB  - Post-Traumatic Stress Disorder (PTSD) is a prevalent, disabling anxiety disorder.
      This prospective cohort study reports on a new exposure-based therapy known as
      Accelerated Resolution Therapy (ART((r))) that incorporates the use of eye
      movements administered in a brief treatment period (1-5 one-hour sessions within
      three weeks). Eighty adults aged 21-60 years with symptoms of PTSD were recruited
      from the Tampa Bay area. The ART-based psychotherapy was designed to minimize
      anxiety and body sensations associated with recall of traumatic memories and to
      replace distressing images with favorable ones. Participants' mean age was 40
      years, 77% were female, and 29% were Hispanic. Participants underwent a median of
      three ART sessions, 66 of 80 (82.5%) completed treatment, and 54 of 66 (81.8%)
      provided 2-month follow-up data. Mean scores pre- and post-ART and at 2-month
      follow-up were: PTSD Checklist: 54.5 +/- 12.2 vs. 31.2 +/- 11.4 vs. 30.0 +/-
      12.4; Brief Symptom Inventory: 30.8 +/- 14.6 vs. 10.1 +/- 10.8 vs. 10.1 +/- 12.1;
      Center for Epidemiologic Studies Depression Scale: 29.5 +/- 10.9 vs. 11.8 +/-
      11.1 vs. 13.5 +/- 12.1; Trauma Related Growth Inventory-Distress scale: 18.9 +/-
      4.1 vs. 7.4 +/- 5.9 vs. 8.2 +/- 5.9 (p < 0.0001 for all pre-ART vs. post-ART and
      2-month comparisons). No serious adverse events were reported. ART appears to be
      a brief, safe, and effective treatment for symptoms of PTSD. 

PMID- 25379219
TI  - Physical and Cognitive Performance of the Least Shrew (Cryptotis parva) on a
      Calcium-Restricted Diet.
AB  - Geological substrates and air pollution affect the availability of calcium to
      mammals in many habitats, including the Adirondack Mountain Region (Adirondacks)
      of the United States. Mammalian insectivores, such as shrews, may be particularly
      restricted in environments with low calcium. We examined the consequences of
      calcium restriction on the least shrew (Cryptotis parva) in the laboratory. We
      maintained one group of shrews (5 F, 5 M) on a mealworm diet with a calcium
      concentration comparable to beetle larvae collected in the Adirondacks (1.1 +/-
      0.3 mg/g) and another group (5 F, 3 M) on a mealworm diet with a calcium
      concentration almost 20 times higher (19.5 +/- 5.1 mg/g). Animals were given no
      access to mineral sources of calcium, such as snail shell or bone. We measured
      running speed and performance in a complex maze over 10 weeks. Shrews on the high
      calcium diet made fewer errors in the maze than shrews on the low-calcium diet
      (F1,14 = 12.8, p < 0.01). Females made fewer errors than males (F1,14 = 10.6, p <
      0.01). Running speeds did not markedly vary between diet groups or sexes, though
      there was a trend toward faster running by shrews on the high calcium diet (p =
      0.087). Shrews in calcium-poor habitats with low availability of mineral sources
      of calcium may have greater difficulty with cognitive tasks such as navigation
      and recovery of food hoards. 

PMID- 25379220
TI  - Psychiatric disorders and substance use in homeless youth: a preliminary
      comparison of san francisco and chicago.
AB  - Youth homelessness is a growing problem in the United States. The experience of
      homelessness appears to have numerous adverse consequences, including psychiatric
      and substance use disorders. This study compared the frequencies of psychiatric
      disorders, including substance use, between homeless youth (18-24 years-old) in
      San Francisco (N = 31) and Chicago (N = 56). Subjects were administered the Mini
      International Neuropsychiatric Interview (M.I.N.I.) to assess DSM-IV-TR diagnoses
      and substance use disorders. Eighty-seven percent of the San Francisco youth, and
      81% of the Chicago youth met criteria for at least one M.I.N.I. psychiatric
      diagnosis. Nearly two-thirds of the youth in both samples met criteria for a mood
      disorder. Approximately one-third met criteria for an anxiety disorder. Thirty
      two percent of the San Francisco sample and 18% of the Chicago met criteria for
      Antisocial Personality Disorder. Approximately 84% of the San Francisco youth and
      48% of the Chicago youth met criteria for a substance-related disorder, and more
      substances were used by San Francisco youth. In conclusion, the high rate of
      psychiatric disorders in homeless youth provides clear evidence that the mental
      health needs of this population are significant. Implications are discussed. 

PMID- 25379221
TI  - Adrenal steroids uniquely influence sexual motivation behavior in male rats.
AB  - The androgenic adrenal steroids dehydroepiandrosterone (DHEA) and 4alpha
      androstenedione (4-A) have significant biological activity, but it is unclear if
      the behavioral effects are unique or only reflections of the effects of
      testosterone (TS). Gonadally intact male Long-Evans rats were assigned to groups
      to receive supplements of DHEA, 4-A, TS, corticosteroid (CORT), all at 400 ug
      steroid/kg of body weight, or vehicle only for 5 weeks. All males were tested in
      a paradigm for sexual motivation that measures time and urinary marks near an
      inaccessible receptive female. It was found that DHEA and 4-A supplements failed
      to influence time near the estrous female in the same way TS supplements did,
      and, indeed, 5 weeks of 4-A administration reduced the time similar to the
      suppressive effects of CORT after 3 weeks. Further, animals treated with DHEA or
      4-A left fewer urinary marks near an estrous female than TS and control groups.
      These results suggest that DHEA and 4-A are not merely precursors of sex
      hormones, and provide support for these steroids influencing the brain and
      behavior in a unique fashion that is dissimilar from the effects of TS on male
      sexual behavior. 

PMID- 25379222
TI  - Working memory, language skills, and autism symptomatology.
AB  - While many studies have reported working memory (WM) impairments in autism
      spectrum disorders, others do not. Sample characteristics, WM domain, and task
      complexity likely contribute to these discrepancies. Although deficits in
      visuospatial WM have been more consistently documented, there is much controversy
      regarding verbal WM in autism. The goal of the current study was to explore
      visuospatial and verbal WM in a well-controlled sample of children with high
      functioning autism (HFA) and typical development. Individuals ages 9-17 with HFA
      (n = 18) and typical development (n = 18), were carefully matched on gender, age,
      IQ, and language, and were administered a series of standardized visuospatial and
      verbal WM tasks. The HFA group displayed significant impairment across WM
      domains. No differences in performance were noted across WM tasks for either the
      HFA or typically developing groups. Over and above nonverbal cognition, WM
      abilities accounted for significant variance in language skills and symptom
      severity. The current study suggests broad WM limitations in HFA. We further
      suggest that deficits in verbal WM are observed in more complex tasks, as well as
      in simpler tasks, such as phonological WM. Increased task complexity and
      linguistic demands may influence WM abilities. 

PMID- 25379223
TI  - Stereotypical behaviors in chimpanzees rescued from the african bushmeat and pet
      trade.
AB  - Many orphaned chimpanzees whose mothers are illegally killed for their meat
      (bushmeat) in Africa are sold as pets or kept caged at hotels and businesses to
      attract tourists. As a result of being separated from their mothers and other
      chimpanzees at an early age, and spending years in impoverished captive
      conditions, some of these individuals engage in abnormal behaviors, including
      stereotypically scratching at their flesh and repetitively rocking back and
      forth. This paper presents case studies of Poco and Safari, two chimpanzees who
      were rescued by sanctuaries after living alone on display for humans at
      businesses for the first 7 to 8 years of their lives. Decades after their rescue,
      they still engage in stereotypical behaviors as a result of the psychological and
      physical trauma they endured early on. This paper combines data from in depth
      interviews with caregivers and direct observations of abnormal behaviors to
      assess psychological distress in captive-living chimpanzees. Our results
      highlight some lesser known harms of the bushmeat trade and the detrimental life
      long consequences that keeping chimpanzees as "pets" can have on their mental
      health. 

PMID- 25379224
TI  - From Augustine of Hippo's Memory Systems to Our Modern Taxonomy in Cognitive
      Psychology and Neuroscience of Memory: A 16-Century Nap of Intuition before Light
      of Evidence.
AB  - Over the last half century, neuropsychologists, cognitive psychologists and
      cognitive neuroscientists interested in human memory have accumulated evidence
      showing that there is not one general memory function but a variety of memory
      systems deserving distinct (but for an organism, complementary) functional
      entities. The first attempts to organize memory systems within a taxonomic
      construct are often traced back to the French philosopher Maine de Biran (1766
      1824), who, in his book first published in 1803, distinguished mechanical memory,
      sensitive memory and representative memory, without, however, providing any
      experimental evidence in support of his view. It turns out, however, that what
      might be regarded as the first elaborated taxonomic proposal is 14 centuries
      older and is due to Augustine of Hippo (354-430), also named St Augustine, who,
      in Book 10 of his Confessions, by means of an introspective process that did not
      aim at organizing memory systems, nevertheless distinguished and commented on
      sensible memory, intellectual memory, memory of memories, memory of feelings and
      passion, and memory of forgetting. These memories were envisaged as different and
      complementary instances. In the current study, after a short biographical
      synopsis of St Augustine, we provide an outline of the philosopher's
      contribution, both in terms of questions and answers, and focus on how this
      contribution almost perfectly fits with several viewpoints of modern psychology
      and neuroscience of memory about human memory functions, including the notion
      that episodic autobiographical memory stores events of our personal history in
      their what, where and when dimensions, and from there enables our mental time
      travel. It is not at all meant that St Augustine's elaboration was the basis for
      the modern taxonomy, but just that the similarity is striking, and that the
      architecture of our current viewpoints about memory systems might have preexisted
      as an outstanding intuition in the philosopher's mind. 

PMID- 25379226
TI  - Problems of teaching the behaviorist perspective in the cognitive revolution.
AB  - This article offers some personal reflections on the difficulty of teaching the
      behaviorist perspective in the psychology classroom. The problems focus on the
      inadequacy of introductory textbooks-which mischaracterize behaviorism, only
      present the most extreme behaviorist positions, make no mention of the
      neobehaviorist perspective, fail to discuss that there is no accepted criteria
      for determining what type of behavior is cognitive, and provide a definition of
      cognition that is, not only inconsistent across texts, but so broad as to
      overshadow the behaviorist contributions. Suggestions are provided for
      instructors on how to present to their students an accurate portrayal of
      behaviorism. 

PMID- 25379225
TI  - Cognition is ... Fundamentally Cultural.
AB  - A prevailing concept of cognition in psychology is inspired by the computer
      metaphor. Its focus on mental states that are generated and altered by
      information input, processing, storage and transmission invites a disregard for
      the cultural dimension of cognition, based on three (implicit) assumptions:
      cognition is internal, processing can be distinguished from content, and
      processing is independent of cultural background. Arguing against each of these
      assumptions, we point out how culture may affect cognitive processes in various
      ways, drawing on instances from numerical cognition, ethnobiological reasoning,
      and theory of mind. Given the pervasive cultural modulation of cognition-on all
      of Marr's levels of description-we conclude that cognition is indeed
      fundamentally cultural, and that consideration of its cultural dimension is
      essential for a comprehensive understanding. 

PMID- 25379227
TI  - Response to hypothetical social scenarios in individuals with traumatic brain
      injury who present inappropriate social behavior: a preliminary report.
AB  - BACKGROUND: Very little research thus far has examined the decision making that
      underlies inappropriate social behavior (ISB) post-TBI (traumatic brain injury).
      OBJECTIVES: To verify the usefulness of a new instrument, the Social Responding
      Task, for investigating whether, in social decision making, individuals with TBI,
      who present inappropriate social behavior (ISB), have difficulty anticipating
      their own feelings of embarrassment and others' angry reactions following an ISB.
      METHODS: Seven subjects with TBI presenting with inappropriate social behavior
      (TBI-ISB), 10 presenting with appropriate social behavior (TBI-ASB), and 15
      healthy controls were given 12 hypothetical scenarios three times, each time
      ending with a different behavioral response. Subjects were asked to gauge the
      likelihood of their displaying the behavior in that situation (part A) and of it
      being followed by an angry reaction from the other or by feelings of
      embarrassment in themselves (part B). RESULTS: TBI-ISB subjects scored higher
      than TBI-ASB and healthy controls on a scale of likelihood of displaying an ISB.
      RESULTS regarding expectations of angry reactions from others and feelings of
      embarrassment after an ISB were similar among groups. Negative correlations
      between endorsement of an inappropriate behavior and anticipation of negative
      emotional consequences were significant for both TBI-ASB and control subjects,
      but not for TBI-ISB subjects. CONCLUSIONS: RESULTS suggest that the TBI-ISB
      participants were likely to endorse an ISB despite being able to anticipate a
      negative emotional response in themselves or others, suggesting that there were
      other explanations for their poor behavior. A self-reported likely response to
      hypothetical social scenarios can be a useful approach for studying the
      neurocognitive processes behind the poor choices of individuals with TBI-ISB, but
      the task needs further validation studies. A comprehensive discussion follows on
      the underlying mechanisms affecting social behaviors after a TBI.

PMID- 25379228
TI  - Long-Term Evaluation of Abnormal Behavior in Adult Ex-laboratory Chimpanzees (Pan
      troglodytes) Following Re-socialization.
AB  - Adverse rearing conditions are considered a major factor in the development of
      abnormal behavior. We investigated the overall levels, the prevalence and the
      diversity of abnormal behavior of 18 adult former laboratory chimpanzees, who
      spent about 20 years single caged, over a two-year period following re
      socialization. According to the onset of deprivation, the individuals were
      classified as early deprived (EDs, mean: 1.2 years) or late deprived (LDs, mean:
      3.6 years). The results are based on 187.5 hours of scan sampling distributed
      over three sample periods: subsequent to re-socialization and during the first
      and second year of group-living. While the overall levels and the diversity of
      abnormal behavior remained stable over time in this study population, the
      amplifying effects of age at onset of deprivation became apparent as the overall
      levels of abnormal behavior of EDs were far above those of LDs in the first and
      second year of group-living, but not immediately after re-socialization. The most
      prevalent abnormal behaviors, including eating disorders and self-directed
      behaviors, however, varied in their occurrence within subjects across the
      periods. Most important, the significance of social companionship became obvious
      as the most severe forms of abnormal behavior, such as dissociative and self
      injurious behaviors declined. 

PMID- 25379229
TI  - Narrowing perceptual sensitivity to the native language in infancy: exogenous
      influences on developmental timing.
AB  - The infancy literature situates the perceptual narrowing of speech sounds at
      around 10 months of age, but little is known about the mechanisms that influence
      individual differences in this developmental milestone. We hypothesized that such
      differences might in part be explained by characteristics of mother-child
      interaction. Infant sensitivity to syllables from their native tongue was
      compared longitudinally to sensitivity to non-native phonemes, at 6 months and
      again at 10 months. We replicated previous findings that at the group level, both
      6- and 10- month-olds were able to discriminate contrasts in their native
      language, but only 6-month-olds succeeded in discriminating contrasts in the non
      native language. However, when discrimination was assessed for separate groups on
      the basis of mother-child interaction-a 'high contingency group' and a 'moderate
      contingency' group-the vast majority of infants in both groups showed the
      expected developmental pattern by 10 months, but only infants in the 'high
      contingency' group showed early specialization for their native phonemes by
      failing to discriminate non-native contrasts at 6-months. The findings suggest
      that the quality of mother-child interaction is one of the exogenous factors
      influencing the timing of infant specialization for speech processing. 

PMID- 25379230
TI  - The search for cognitive terminology: an analysis of comparative psychology
      journal titles.
AB  - This research examines the employment of cognitive or mentalist words in the
      titles of articles from three comparative psychology journals (Journal of
      Comparative Psychology, International Journal of Comparative Psychology, Journal
      of Experimental Psychology: Animal Behavior Processes; 8,572 titles, >100,000
      words). The Dictionary of Affect in Language, coupled with a word search of
      titles, was employed to demonstrate cognitive creep. The use of cognitive
      terminology increased over time (1940-2010) and the increase was especially
      notable in comparison to the use of behavioral words, highlighting a
      progressively cognitivist approach to comparative research. Problems associated
      with the use of cognitive terminology in this domain include a lack of
      operationalization and a lack of portability. There were stylistic differences
      among journals including an increased use of words rated as pleasant and concrete
      across years for Journal of Comparative Psychology, and a greater use of
      emotionally unpleasant and concrete words in Journal of Experimental Psychology:
      Animal Behavior Processes. 

PMID- 25379231
TI  - An overview of the first use of the terms cognition and behavior.
AB  - Use of the terms cognition and behavior and their variants can be traced back to
      the middle-ages. What is not widely known is how the terms were first used in the
      literature. This article identifies variations of terms for cognition and
      behavior and traces the first use of the terms using the Oxford English
      Dictionary (OED). A systematic search of the OED was conducted, identifying terms
      in the cognition and behavior families. Terms are defined and the year the term
      first appeared in the literature is identified. Terms are sorted and grouped
      chronologically by first appearance to determine their first use in the
      literature as noted in the OED. Results indicated more words are related to
      cognition than behavior. The first term related to cognition to appear was
      cogitation in circa 1225; while the first term related to behavior was port,
      which appeared circa 1330. Each family of terms experienced tremendous growth
      during the first appearance of terms. The cognition family saw 60% of its terms
      appear in the 17(th) and 19(th) centuries. The behavior family saw nearly 75% of
      its terms make their first appearance during the 15(th) through the 17(th)
      centuries. 

PMID- 25379232
TI  - What do We Know about Neonatal Cognition?
AB  - Research on neonatal cognition has developed very recently in comparison with the
      long history of research on child behavior. The last sixty years of research have
      provided a great amount of evidence for infants' numerous cognitive abilities.
      However, only little of this research concerns newborn infants. What do we know
      about neonatal cognition? Using a variety of paradigms, researchers became able
      to probe for what newborns know. Amongst these results, we can distinguish
      several levels of cognitive abilities. First, at the perceptual or sensory level,
      newborns are able to process information coming from the social world and the
      physical objects through all their senses. They are able to discriminate between
      object shapes and between faces; that is, they are able to detect invariants,
      remember and recognize them. Second, newborns are able to abstract information,
      to compare different inputs and to match them across different sensory
      modalities. We will argue that these two levels can be considered high-level
      cognitive abilities: they constitute the foundations of human cognition.
      Furthermore, while some perceptual competencies can stem from the fetal period,
      many of these perceptual and cognitive abilities cannot be a consequence of the
      environment surrounding the newborn before birth. 

PMID- 25379233
TI  - Everyday problem solving and instrumental activities of daily living: support for
      domain specificity.
AB  - Research suggests that performance on cognitive tasks resembling daily challenges
      (i.e., everyday problem-solving tasks) may be a better indicator of functional
      ability in old age compared to traditional measures of cognitive ability.
      Findings demonstrating this link, however, have yielded mixed results. The
      current study examined performance on the Everyday Problems Test (EPT) and self
      reported ability to perform Instrumental Activities of Daily Living (IADLs) in a
      sample of adults over age 50. The EPT measures cognitive performance on tasks
      with domains consistent with IADLs (telephone use, shopping, meal preparation,
      housekeeping, transportation, health and finances). Although overall EPT scores
      and self-reported IADLs were significantly related (rs = 0.20; p < 0.05),
      additional analyses revealed that domain-specific EPT performance related to IADL
      reports within the same domain for shopping, meal preparation, housekeeping, and
      financial management after accounting for other variables such as age, sex, and
      measures of cognitive ability including total EPT score. These findings suggest
      that domain-specific performance on cognitive everyday problem-solving tasks may
      add to the predictability of specific IADLs. 

PMID- 25379235
TI  - Mill and mental phenomena: critical contributions to a science of cognition.
AB  - Attempts to define cognition preceded John Stuart Mill's life and continue to
      this day. John Stuart Mill envisioned a science of mental phenomena informed by
      associationism, empirical introspection, and neurophysiology, and he advanced
      specific ideas that still influence modern conceptions of cognition. The present
      article briefly reviews Mill's personal history and the times in which he lived,
      and it traces the evolution of ideas that have run through him to contemporary
      cognitive concepts. The article also highlights contemporary problems in defining
      cognition and supports specific criteria regarding what constitutes cognition. 

PMID- 25379234
TI  - Distinct episodic verbal memory profiles in schizophrenia.
AB  - According to some authors, episodic memory impairment may be a feature shared by
      all schizophrenic patients, whereas others argue in favor of the mnesic
      heterogeneity. Our aims were to determine whether patients can be grouped based
      on according to their mnesic performances. The California Verbal Learning Test
      (CVLT), an episodic verbal learning test, was compared in 61 schizophrenic
      patients and 61 matched healthy subjects. The 32 indices were calculated using
      CVLT Scoring Software. This process allowed us to describe patients' episodic
      processes in detail (encoding, storage, retrieval). We isolated one group with
      normative data, another showed impairment of both encoding and retrieval
      processes, and in the last one, only encoding process was impaired. As
      schizophrenia is heterogeneous with regard to episodic memory, impairments should
      not be considered as a common core to the various forms of the illness and it
      would be fruitful to systematically assess episodic processes in detail to take
      into account individual abilities and challenges. 

PMID- 25379236
TI  - St. Augustine's Reflections on Memory and Time and the Current Concept of
      Subjective Time in Mental Time Travel.
AB  - Reconstructing the past and anticipating the future, i.e., the ability of
      travelling in mental time, is thought to be at the heart of consciousness and, by
      the same token, at the center of human cognition. This extraordinary mental
      activity is possible thanks to the ability of being aware of 'subjective time'.
      In the present study, we attempt to trace back the first recorded reflections on
      the relations between time and memory, to the end of the fourth century's work,
      the Confessions, by the theologian and philosopher, St. Augustine. We concentrate
      on Book 11, where he extensively developed a series of articulated and detailed
      observations on memory and time. On the bases of selected paragraphs, we endeavor
      to highlight some concepts that may be considered as the product of the first or,
      at least, very early reflections related to our current notions of subjective
      time in mental time travel. We also draw a fundamental difference inherent to the
      frameworks within which the questions were raised. The contribution of St.
      Augustine on time and memory remains significant, notwithstanding the 16
      centuries elapsed since it was made, likely because of the universality of its
      contents. 

PMID- 25379237
TI  - The reality monitoring deficit as a common neuropsychological correlate of
      schizophrenic and affective psychosis.
AB  - For many decades, Neuropsychological functioning has been a key point in the
      study of psychotic disorders. The main aim of these studies is to give a
      description of the neurocognitive "profile" of schizophrenia, with only little
      attention being paid to the common and discriminating features of different
      psychotic disorders. Recent studies support the hypothesis that patients affected
      by psychiatric disorders with psychotic symptoms have specific abnormalities of
      reality testing of ongoing perception, which become evident with source
      monitoring task. Ninety-eight patients and 50 controls were studied. Patients
      were divided by diagnosis and previous history of psychotic features and were
      administered Source Monitoring Task to test reality testing of ongoing
      perception. Frequencies of correct and false attributions were recorded. To
      obtain measures of observer sensitivity and response biases, a signal detection
      analysis was performed. AIMS: Studying neuropsychological correlate of psychosis
      in euthymic mood disordered patients and patients with schizophrenia with or
      without delusions. RESULTS: Patients with psychotic features use more lax
      criteria in evaluating self-generated, but not perceived stimuli compared to
      patients without psychotic features. CONCLUSIONS: Our findings support the
      hypothesis of selective biases in reality monitoring as neuropsychological
      correlates of psychosis.

PMID- 25379238
TI  - Systems biology as a comparative approach to understand complex gene expression
      in neurological diseases.
AB  - Systems biology interdisciplinary approaches have become an essential analytical
      tool that may yield novel and powerful insights about the nature of human health
      and disease. Complex disorders are known to be caused by the combination of
      genetic, environmental, immunological or neurological factors. Thus, to
      understand such disorders, it becomes necessary to address the study of this
      complexity from a novel perspective. Here, we present a review of integrative
      approaches that help to understand the underlying biological processes involved
      in the etiopathogenesis of neurological diseases, for example, those related to
      autism and autism spectrum disorders (ASD) endophenotypes. Furthermore, we
      highlight the role of systems biology in the discovery of new biomarkers or
      therapeutic targets in complex disorders, a key step in the development of
      personalized medicine, and we demonstrate the role of systems approaches in the
      design of classifiers that can shorten the time for behavioral diagnosis of
      autism. 

PMID- 25379239
TI  - Discrimination within Recognition Memory in Schizophrenia.
AB  - Episodic memory is one of the most affected cognitive domains in schizophrenia.
      First-degree biological relatives of individuals with schizophrenia also have
      been found to exhibit a similar, but milder, episodic memory deficit. Unlike most
      studies that focus on the percent of previously presented items recognized, the
      current investigation sought to further elucidate the nature of memory
      dysfunction associated with schizophrenia by examining the discrimination of old
      and new material during recognition (measured by d') to consider false
      recognition of new items. Using the Recurring Figures Test and the California
      Verbal Learning Test (CVLT), we studied a sample of schizophrenia probands and
      the first-degree biological relatives of patients with schizophrenia, as well as
      probands with bipolar disorder and first-degree biological relatives to assess
      the specificity of recognition memory dysfunction to schizophrenia. The
      schizophrenia sample had poorer recognition discrimination in both nonverbal and
      verbal modalities; no such deficits were identified in first-degree biological
      relatives or bipolar disorder probands. Discrimination in schizophrenia and
      bipolar probands failed to benefit from the geometric structure in the designs in
      the manner that controls did on the nonverbal test. Females performed better than
      males in recognition of geometric designs. Episodic memory dysfunction in
      schizophrenia is present for a variety of stimulus domains and reflects poor use
      of item content to increase discrimination of old and new items. 

PMID- 25379241
TI  - The impact of precaution and practice on the performance of a risky motor task.
AB  - The association between threat perception and motor execution, mediated by
      evolved precaution systems, often results in ritual-like behavior, including many
      idiosyncratic acts that seem irrelevant to the task at hand. This study tested
      the hypothesis that threat-detection during performance of a risky motor task
      would result in idiosyncratic activity that is not necessary for task completion.
      We asked biology students to follow a particular set of instructions in mixing
      three solutions labeled "bio-hazardous" and then repeat this operation with "non
      hazardous" substances (or vice versa). We observed a longer duration of the
      overall performance, a greater repertoire of acts, longer maximal act duration,
      and longer mean duration of acts in the "risky" task when it was performed before
      the "non-risky" task. Some, but not all, of these differences were eliminated
      when a "non-risky" task preceded the "risky" one. The increased performance of
      idiosyncratic unnecessary activity is in accordance with the working hypothesis
      of the present study: ritualized idiosyncratic activities are performed in
      response to a real or illusionary threat, as a means to alleviate anxiety. 

PMID- 25379240
TI  - Hippocampal physiology, structure and function and the neuroscience of
      schizophrenia: a unified account of declarative memory deficits, working memory
      deficits and schizophrenic symptoms.
AB  - Memory impairment is a consistent feature of the schizophrenic syndrome.
      Hippocampal dysfunction has also been consistently demonstrated. This review will
      discuss neurophysiological and neuroanatomical aspects of memory formation and
      how they relate to memory impairment in schizophrenia. An understanding of the
      cellular physiology and connectivity of the hippocampus with other regions can
      also aid in understanding the relationship between schizophrenic declarative or
      relational memory deficits, working memory deficits and the clinical symptoms of
      the syndrome. 

PMID- 25379243
TI  - Emotional verbal fluency: a new task on emotion and executive function
      interaction.
AB  - The present study introduces "Emotional Verbal Fluency" as a novel (partially
      computerized) task, which is aimed to investigate the interaction between
      emotionally loaded words and executive functions. Verbal fluency tasks are
      thought to measure executive functions but the interaction with emotional aspects
      is hardly investigated. In the current study, a group of healthy subjects (n =
      21, mean age 25 years, 76% females) were asked to generate items that are either
      part of a semantic category (e.g., plants, toys, vehicles; standard semantic
      verbal fluency) or can trigger the emotions joy, anger, sadness, fear and
      disgust. The results of the task revealed no differences between performance on
      semantic and emotional categories, suggesting a comparable task difficulty for
      healthy subjects. Hence, these first results on the comparison between semantic
      and emotional verbal fluency seem to highlight that both might be suitable for
      examining executive functioning. However, an interaction was found between the
      category type and repetition (first vs. second sequence of the same category)
      with larger performance decrease for semantic in comparison to emotional
      categories. Best performance overall was found for the emotional category "joy"
      suggesting a positivity bias in healthy subjects. To conclude, emotional verbal
      fluency is a promising approach to investigate emotional components in an
      executive task, which may stimulate further research, especially in psychiatric
      patients who suffer from emotional as well as cognitive deficits. 

PMID- 25379242
TI  - Memory deficits in schizophrenia: a selective review of functional magnetic
      resonance imaging (FMRI) studies.
AB  - Schizophrenia is a complex chronic mental illness that is characterized by
      positive, negative and cognitive symptoms. Cognitive deficits are most predictive
      of long-term outcomes, with abnormalities in memory being the most robust
      finding. The advent of functional magnetic resonance imaging (fMRI) has allowed
      exploring neural correlates of memory deficits in vivo. In this article, we will
      give a selective review of fMRI studies probing brain regions and functional
      networks that are thought to be related to abnormal memory performance in two
      memory systems prominently affected in schizophrenia; working memory and episodic
      memory. We revisit the classic "hypofrontality" hypothesis of working memory
      deficits and explore evidence for frontotemporal dysconnectivity underlying
      episodic memory abnormalities. We conclude that fMRI studies of memory deficits
      in schizophrenia are far from universal. However, the current literature does
      suggest that alterations are not isolated to a few brain regions, but are
      characterized by abnormalities within large-scale brain networks. 

PMID- 25379245
TI  - Jung's "Psychology with the Psyche" and the Behavioral Sciences.
AB  - The behavioral sciences and Jung's analytical psychology are set apart by virtue
      of their respective histories, epistemologies, and definitions of subject matter.
      This brief paper identifies Jung's scientific stance, notes perceptions of Jung
      and obstacles for bringing his system of thought into the fold of the behavioral
      sciences. The impact of the "science versus art" debate on Jung's stance is
      considered with attention to its unfolding in the fin de siecle era. 

PMID- 25379244
TI  - Applying evolutionary thinking to the study of emotion.
AB  - This paper argues for invoking evolutionary, functional thinking in analyzing
      emotions. It suggests that the fitness needs of normal individuals be kept in
      mind when trying to understand emotional behavior. This point of view is
      elaborated in sections addressing these topics: defining emotion; applying
      comparative analysis to the study of emotions; focusing on the elicitors and
      resulting motivated behaviors mediated by the various affects; recognizing that
      not all emotions have prominent, distinct facial expressions; acknowledging all
      of the basic emotions and not just some exemplars; crediting the more sensible
      Cannon-Bard theory over James-Lange; recognizing the more ancient, fundamental
      role of the limbic system in emotion compared with that of the neocortex; and
      analyzing socio-emotional interactions as they occur naturally, not just
      individual emotional behavior studied under artificial conditions. Describing the
      various facets and neuroendocrine mechanisms of each basic emotion can provide a
      framework for understanding the normal and pathological development of each
      emotion. Such an inventory, or ethogram, would provide a comprehensive list of
      all of the observable behavioral tendencies of our species. 

PMID- 25379246
TI  - Psychological Detachment in the Relationship between Job Stressors and Strain.
AB  - We investigated the mediating versus moderating role of psychological detachment
      in the relationship between job stressors and psychological strain. Our sample
      consisted of 173 university students invested in challenging programs of advanced
      professional studies, who could find it difficult to detach from work.
      Hierarchical regression analyses of cross-sectional survey data affirmed the role
      of psychological detachment as a mediator in the relationship between job demands
      and perceived stress. Detachment also mediated the relationship between job
      demands and satisfaction with life, although the association disappeared when
      controlling for negative affectivity. Detachment did not mediate relationships
      between job demands and cognitive failures. Psychological detachment did not
      moderate any of the investigated relationships. The study contributes to a view
      of psychological detachment as less subject to individual differences than to the
      imposition of stressors in the given context. 

PMID- 25379247
TI  - Traumatic brain injury, boredom and depression.
AB  - Traumatic brain injury (TBI) often presents with co-morbid depression and
      elevated levels of boredom. We explored the relationship between boredom and
      depression in a group of mild (n = 38), moderate-to-severe TBI patients (n = 14)
      and healthy controls (n = 88), who completed the Beck Depression Inventory and
      Boredom Proneness Scales as part of a larger study. Results showed that the
      relationship between boredom and depression was strongest in moderate-to-severe
      TBI patients. We explored two boredom proneness factors that index an
      individual's need for external or internal stimulation. Results indicated that
      the need for external stimulation was the critical driver in the relation between
      boredom and depression. Once again, this relationship was strongest in the
      moderate-to-severe TBI group. These results suggest that one common factor
      underlying boredom and depression is the need for stimulation from the external
      environment and, presumably, a failure to satisfy that need-a disconnection felt
      most strongly in moderate-to-severe TBI. 

PMID- 25379248
TI  - Nausea in specific phobia of vomiting.
AB  - Specific phobia of vomiting (SPOV) is a clinical condition with early onset,
      chronic course and substantial psychosocial impairment due to a rigorous
      avoidance behavior. A primary symptom which drives patients to consult a medical
      practitioner is nausea. In this study our aim was to further analyze this symptom
      of SPOV and examined its role in the development and manifestation of the phobia.
      We conducted an internet survey in the german SPOV-internet-forum. We calculated
      a nausea score and grouped participants in a high-and low-nausea group to examine
      the relationship between nausea and characteristics of the fear of vomiting. In
      this sample (N = 131), nausea was fairly common in most participants with fear of
      vomiting. Participants in the high-nausea group had significantly higher ratings
      of subjective fear and significantly longer duration of fear of vomiting.
      Additionally, the high-nausea group contained more participants with a body mass
      index below 19 than the low-nausea group. The present findings suggest that
      nausea is a core symptom in SPOV which is closely related to intensity of the
      fear, duration of the fear, and body weight. Future research should investigate
      if nausea-specific design of treatment could improve therapy outcome. 

PMID- 25379249
TI  - On the function of boredom.
AB  - Boredom is frequently considered inconsequential and has received relatively
      little research attention. We argue that boredom has important implications for
      human functioning, based on emotion theory and empirical evidence. Specifically,
      we argue that boredom motivates pursuit of new goals when the previous goal is no
      longer beneficial. Exploring alternate goals and experiences allows the
      attainment of goals that might be missed if people fail to reengage. Similar to
      other discrete emotions, we propose that boredom has specific and unique impacts
      on behavior, cognition, experience and physiology. Consistent with a broader
      argument that boredom encourages the behavioral pursuit of alternative goals, we
      argue that, while bored, attention to the current task is reduced, the experience
      of boredom is negative and aversive, and that boredom increases autonomic arousal
      to ready the pursuit of alternatives. By motivating desire for change from the
      current state, boredom increases opportunities to attain social, cognitive,
      emotional and experiential stimulation that could have been missed. We review the
      limited extant literature to support these claims, and call for more experimental
      boredom research. 

PMID- 25379250
TI  - Explaining Differential Reporting of Victimization between Parents and Children:
      A Consideration of Social Biases.
AB  - Studies have shown that children and parents provide different reports of
      children's victimization, with children often reporting more victimization.
      However, the reason for this differential reporting is unclear. This study
      explored two types of social biases (emotion recognition and perceived
      impairment) in parents and children as possible reasons underlying differential
      reporting. Six- to 10-year-old children and one of their parents were tested in a
      lab. Testing included subjective measures of parent alexithymic traits, child
      perceived impairment from victimization, and child- and parent-reported frequency
      of children's peer victimization and internalizing and externalizing
      difficulties. Parents and children also completed an objective measure of emotion
      recognition. Both types of social bias significantly predicted reports of
      children's peer victimization frequency as well as internalizing and
      externalizing difficulties, as rated by parents and children. Moreover, child
      perceived impairment bias, rather than parent emotion bias, best predicted
      differential reporting of peer victimization. Finally, a significant interaction
      demonstrated that the influence of child perceived impairment bias on
      differential reporting was most salient in the presence of parent emotion bias.
      This underscores the importance of expanding interventions for victimized youth
      to include the restructuring of social biases. 

PMID- 25379251
TI  - Beatrice hinkle and the early history of jungian psychology in new york.
AB  - As the leading proponent of psychoanalysis, Jung made trips to New York in 1912
      and 1913. The first was to give his Fordham lectures, the second has escaped
      notice but was crucial in the early dissemination of Jungian psychology in the
      U.S. This paper will elaborate on this development by highlighting the career and
      influence of Beatrice Hinkle, the country's first Jungian psychoanalyst. She was
      an M.D. and ardent feminist who introduced Jung to her Greenwich Village circle,
      translated his magnum opus Transformations and Symbols of the Libido, and helped
      establish the institutional basis of Jungian psychology in America. 

PMID- 25379252
TI  - On the evolution and optimality of mood States.
AB  - Moods can be regarded as fluctuating dispositions to make positive and negative
      evaluations. Developing an evolutionary approach to mood as an adaptive process,
      we consider the structure and function of such states in guiding behavioural
      decisions regarding the acquisition of resources and the avoidance of harm in
      different circumstances. We use a drift diffusion model of decision making to
      consider the information required by individuals to optimise decisions between
      two alternatives, such as whether to approach or withdraw from a stimulus that
      may be life enhancing or life threatening. We show that two dimensions of
      variation (expectation and preparedness) are sufficient for such optimal
      decisions to be made. These two dispositional dimensions enable individuals to
      maximize the overall benefits of behavioural decisions by modulating both the
      choice made (e.g., approach/withdraw) and decision speed. Such a structure is
      compatible with circumplex models of subjectively experienced mood and core
      affect, and provides testable hypotheses concerning the relationships that occur
      between valence and arousal components of mood in differing ecological niches.
      The paper is therefore a useful step toward being able to predict moods (and the
      effect of moods) using an optimality approach. 

PMID- 25379253
TI  - Cognitive predictors of verbal memory in a mixed clinical pediatric sample.
AB  - Verbal memory problems, along with other cognitive difficulties, are common in
      children diagnosed with neurological and/or psychological disorders.
      Historically, these "memory problems" have been poorly characterized and often
      present with a heterogeneous pattern of performance across memory processes, even
      within a specific diagnostic group. The current study examined archival
      neuropsychological data from a large mixed clinical pediatric sample in order to
      understand whether functioning in other cognitive areas (i.e., verbal knowledge,
      attention, working memory, executive functioning) may explain some of the
      performance variability seen across verbal memory tasks of the Children's Memory
      Scale (CMS). Multivariate analyses revealed that among the cognitive functions
      examined, only verbal knowledge explained a significant amount of variance in
      overall verbal memory performance. Further univariate analyses examining the
      component processes of verbal memory indicated that verbal knowledge is
      specifically related to encoding, but not the retention or retrieval stages.
      Future research is needed to replicate these findings in other clinical samples,
      to examine whether verbal knowledge predicts performance on other verbal memory
      tasks and to explore whether these findings also hold true for visual memory
      tasks. Successful replication of the current study findings would indicate that
      interventions targeting verbal encoding deficits should include efforts to
      improve verbal knowledge. 

PMID- 25379254
TI  - Functional perspectives on emotion, behavior, and cognition.
AB  - This Editorial reviews the challenges and advantages posed by a functional
      perspective on the relationships among emotion, behavior, and cognition. We
      identify the core themes among the articles published as part of this Special
      Issue. The articles generally address two important questions: (1) are emotions
      functional and what is their impact on behavioral and cognitive processes, and
      (2) how do the interactions among emotion, cognition, and behavior play out in
      particular situations that present adaptive challenges? We also identify two core
      questions raised by the articles included in this Special Issue. Future research
      must address the extent to which emotions are best represented as discrete
      emotional constructs (e.g., anger, sadness, fear) versus emotions that vary along
      dimensions, such as valence and arousal. Functional perspectives would also be
      facilitated by identification of situations or environments that are likely to
      elicit particular emotions and reactions. 

PMID- 25379255
TI  - Symbol/Meaning paired-associate recall: an "archetypal memory" advantage?
AB  - The theory of the archetypes and the hypothesis of the collective unconscious are
      two of the central characteristics of analytical psychology. These provoke,
      however, varying reactions among academic psychologists. Empirical studies which
      test these hypotheses are rare. Rosen, Smith, Huston and Gonzales proposed a
      cognitive psychological experimental paradigm to investigate the nature of
      archetypes and the collective unconscious as archetypal (evolutionary) memory. In
      this article we report the results of a cross-cultural replication of Rosen et
      al. conducted in the German-speaking part of Switzerland. In short, this
      experiment corroborated previous findings by Rosen et al., based on English
      speakers, and demonstrated a recall advantage for archetypal symbol meaning pairs
      vs. other symbol/meaning pairings. The fact that the same pattern of results was
      observed across two different cultures and languages makes it less likely that
      they are attributable to a specific cultural or linguistic context. 

PMID- 25379256
TI  - Evidence for the effectiveness of jungian psychotherapy: a review of empirical
      studies.
AB  - Since the 1990s several research projects and empirical studies (process and
      outcome) on Jungian Psychotherapy have been conducted mainly in Germany and
      Switzerland. Prospective, naturalistic outcome studies and retrospective studies
      using standardized instruments and health insurance data as well as several
      qualitative studies of aspects of the psychotherapeutic process will be
      summarized. The studies are diligently designed and the results are well
      applicable to the conditions of outpatient practice. All the studies show
      significant improvements not only on the level of symptoms and interpersonal
      problems, but also on the level of personality structure and in every day life
      conduct. These improvements remain stable after completion of therapy over a
      period of up to six years. Several studies show further improvements after the
      end of therapy, an effect which psychoanalysis has always claimed. Health
      insurance data show that, after Jungian therapy, patients reduce health care
      utilization to a level even below the average of the total population. Results of
      several studies show that Jungian treatment moves patients from a level of severe
      symptoms to a level where one can speak of psychological health. These
      significant changes are reached by Jungian therapy with an average of 90
      sessions, which makes Jungian psychotherapy an effective and cost-effective
      method. Process studies support Jungian theories on psychodynamics and elements
      of change in the therapeutic process. So finally, Jungian psychotherapy has
      reached the point where it can be called an empirically proven, effective method.

PMID- 25379257
TI  - A desire for parsimony.
AB  - An understanding of wildness is being developed as a quality of interactive
      processing that increases survival opportunities in nature. A link is made
      between the need to improve interactive quality for wildness, and cognitive
      desires and interests in art, music, religion and philosophy as these can also be
      seen as attempts to improve interactive quality internally and externally.
      Interactive quality can be improved through gains in parsimony, that is,
      simplifications in the organisation of skills. The importance of parsimony in
      evolution is discussed, along with indicators of an internal parsimony desire
      that experiences joy if achieved through processes such as insight and
      understanding. A mechanism for the production and measurement of the parsimony
      desire is proposed, based on the number of subcortical pleasure hotspots that can
      be stimulated at once within the 'archipelago' available in the limbic system. 

PMID- 25379259
TI  - Carl gustav jung, quantum physics and the spiritual mind: a mystical vision of
      the twenty-first century.
AB  - We describe similarities in the ontology of quantum physics and of Carl Gustav
      Jung's psychology. In spite of the fact that physics and psychology are usually
      considered as unrelated, in the last century, both of these disciplines have led
      at the same time to revolutionary changes in the Western understanding of the
      cosmic order, discovering a non-empirical realm of the universe that doesn't
      consist of material things but of forms. These forms are real, even though they
      are invisible, because they have the potential to appear in the empirical world
      and act in it. We present arguments that force us to believe, that the empirical
      world is an emanation out of a cosmic realm of potentiality, whose forms can
      appear as physical structures in the external world and as archetypal concepts in
      our mind. Accordingly, the evolution of life now appears no longer as a process
      of the adaptation of species to their environment, but as the adaptation of minds
      to increasingly complex forms that exist in the cosmic potentiality. The cosmic
      connection means that the human mind is a mystical mind. 

PMID- 25379258
TI  - Psychological distress and post-traumatic symptoms following occupational
      accidents.
AB  - Depression and post-traumatic stress disorder frequently occur as a consequence
      of occupational accidents. To date, research has been primarily focused on high
      risk workers, such as police officers or firefighters, and has rarely considered
      individuals whose occupational environment involves the risk of severe, but not
      necessarily life-threatening, injury. Therefore, the present study was aimed at
      assessing the psychological consequences of accidents occurring in several
      occupational settings (e.g., construction and industry). Thirty-eight victims of
      occupational accidents (injured workers) and 38 gender-, age-, and years of
      education-matched workers who never experienced a work accident (control group)
      were recruited. All participants underwent a semi-structured interview
      administered by a trained psychologist, and then were requested to fill in the
      questionnaires. Injured workers reported more severe anxious, post-traumatic and
      depressive symptoms, and poorer coping skills, as compared to controls. In the
      injured group low levels of resilience predicted post-traumatic symptomatology,
      whereas the degree of physical injury and the length of time since the accident
      did not play a predictive role. The results suggest that occupational accidents
      may result in a disabling psychopathological condition, and that a brief
      psychological evaluation should be included in the assessment of seriously
      injured workers. 

PMID- 25379260
TI  - Accounting for material reality in the analytic subject.
AB  - Scientific advances made in the 21st century contend that the forces of nature
      and nurture work together through an ongoing series of complex correspondences
      between brain and mental activity in our daily activities with others. Jung's
      cosmological model of the psyche minimizes the fundamental corporeal condition of
      human nature and as such is critiqued and amended, influenced by the
      transcendental materialist theories of subjectivity inspired by Zizek, Johnston
      and Laplanche. 

PMID- 25379261
TI  - The Dialogical Jung: Otherness within the Self.
AB  - This paper explores dialogical currents in Jung's analytical psychology, with
      reference to contemporary theories of the dialogical self. The dialogical self is
      a notion that has gained increasing currency in psychology since the 1990s, in
      response to the limitations of traditional notions of the self, based on
      monological, encapsulated consciousness. Modern dialogical self theory construes
      the self as irrevocably embedded in a matrix of real and imagined dialogues with
      others. The theme of dialogical otherness within the self is also taken up in
      Jung's analytical psychology, both in the practice of active imagination and
      psychotherapy and in the theory of archetypes, and a dialogical approach to
      inquiry is evident in Jung's work from the outset. The implications of a
      dialogical re-conceptualization of analytical psychology and of analytical
      psychology for dialogical theory are considered in detail. 

PMID- 25379262
TI  - Normality in analytical psychology.
AB  - Although C.G. Jung's interest in normality wavered throughout his career, it was
      one of the areas he identified in later life as worthy of further research. He
      began his career using a definition of normality which would have been the target
      of Foucault's criticism, had Foucault chosen to review Jung's work. However, Jung
      then evolved his thinking to a standpoint that was more aligned to Foucault's
      own. Thereafter, the post Jungian concept of normality has remained relatively
      undeveloped by comparison with psychoanalysis and mainstream psychology. Jung's
      disjecta membra on the subject suggest that, in contemporary analytical
      psychology, too much focus is placed on the process of individuation to the
      neglect of applications that consider collective processes. Also, there is
      potential for useful research and development into the nature of conflict between
      individuals and societies, and how normal people typically develop in relation to
      the spectrum between individuation and collectivity. 

PMID- 25379263
TI  - Jung on the nature and interpretation of dreams: a developmental delineation with
      cognitive neuroscientific responses.
AB  - Post-Jungians tend to identify Jung's dream theory with the concept of
      compensation; they tend to believe that Jung's radically open stand constitutes
      his dream theory in its entirety. However, Jung's theory regarding dreams was a
      product of an evolving process throughout his whole intellectual and professional
      life. Unfortunately, the theory has not been understood in such a developmental
      light. Based on a historical and textual study of all dream articles found
      throughout The Collected Works of C.G. Jung, this paper maps a concise three
      phase trajectory of Jung's changing views on dreams and interpretation. The paper
      posits that Jung's last essay, "Symbols and the Interpretation of Dreams" (1961),
      epitomizes his final stand, although such a stand is also reflected in a less
      explicit and less emphatic way during the latter period of the second phase. The
      paper also briefly addresses where Jung and Jungians have been enigmatic or
      negligent. For example, it has not been explicated fully why compensation as
      slight modifications and compensation as parallels to waking life situations are
      rare in Jung's cases In addition, contemporary cognitive and neuroscientific
      approaches to the study of dreams, as represented by Harry Hunt, William Domhoff,
      and Allan Hobson, among others, are presented in connection with Jung. The
      juxtaposition of Jungian, cognitive, and neuroscientific approaches showcases how
      cognitive and scientific findings challenge, enrich, and in some ways confirm
      Jung's dream theory and praxis. 

PMID- 25379264
TI  - Archetypal-imaging and mirror-gazing.
AB  - Mirrors have been studied by cognitive psychology in order to understand self
      recognition, self-identity, and self-consciousness. Moreover, the relevance of
      mirrors in spirituality, magic and arts may also suggest that mirrors can be
      symbols of unconscious contents. Carl G. Jung investigated mirrors in relation to
      the unconscious, particularly in Psychology and Alchemy. However, the
      relationship between the conscious behavior in front of a mirror and the
      unconscious meaning of mirrors has not been clarified. Recently, empirical
      research found that gazing at one's own face in the mirror for a few minutes, at
      a low illumination level, produces the perception of bodily dysmorphic illusions
      of strange-faces. Healthy observers usually describe huge distortions of their
      own faces, monstrous beings, prototypical faces, faces of relatives and deceased,
      and faces of animals. In the psychiatric population, some schizophrenics show a
      dramatic increase of strange-face illusions. They can also describe the
      perception of multiple-others that fill the mirror surface surrounding their
      strange-face. Schizophrenics are usually convinced that strange-face illusions
      are truly real and identify themselves with strange-face illusions, diversely
      from healthy individuals who never identify with them. On the contrary, most
      patients with major depression do not perceive strange-face illusions, or they
      perceive very faint changes of their immobile faces in the mirror, like death
      statues. Strange-face illusions may be the psychodynamic projection of the
      subject's unconscious archetypal contents into the mirror image. Therefore,
      strange-face illusions might provide both an ecological setting and an
      experimental technique for "imaging of the unconscious". Future researches have
      been proposed. 

PMID- 25379265
TI  - Gender legacies of jung and freud as epistemology in emergent feminist research
      on late motherhood.
AB  - While conducting doctoral research in social science on late motherhood, two
      analytical engagements with the feminine came to my attention as evidence of a
      patriarchal bias toward the realm of womanhood. Jung's mythopoetic tension
      between symbolism and enactments with the feminine and Freud's supposition that a
      denial of the feminine was necessary for psychological and emotional development
      appeared to be perpetuating a social problem continuing in current times. Across
      affective behavior and narrative within stories of late procreative desire, dream
      journals and Word Association Tests of eight participants was the memory of a
      male sibling who had enjoyed primacy of place in the parental home over the
      daughter. The female body with a voice was missing in the one-sided perspectives
      of Analytical Psychology and Psychoanalysis on the subject of the feminine, until
      a whole view of psyche's discontents in Feminist inspired Psychoanalytic theories
      from both schools on the female body were included. Freud and Jung's views became
      evidence of patriarchy as background while extension of Feminist inspired
      psychoanalytical thinking, Queer theories and Creation Myth allowed new meanings
      of the embodied feminine to emerge through a recapitulation of a union of
      opposites as a union of epistemology and ethos. The essence of Jung's mid-life
      theories, altered by modernity and eclipsed by female advancement, remains
      replicatable and paradigmatic outside of essentialist gender performance. 

PMID- 25379266
TI  - Effectiveness of Group-Delivered Cognitive Therapy and Treatment Length in Women
      Veterans with PTSD.
AB  - The effectiveness and length of group-delivered cognitive treatment for
      Posttraumatic Stress Disorder (PTSD) was examined in a sample of women veterans.
      The sample included 271 primarily non-Hispanic white (61%) and Hispanic (25%)
      women veterans treated in 8-, 10-, or 12-group length sessions with manualized
      cognitive therapy for PTSD. Outcome was measured with the PTSD Symptom Checklist
      (PCL) in an intention-to-treat analysis (N = 271), in completer subjects (n =
      172), and with group as the unit of analysis (n = 47 groups). Significant
      decreases in PTSD were found in the full sample (effect size [ES] range = 0.27 to
      0.38), completers (ES range = 0.37 to 0.54), and group as the unit of analysis
      (ES range = 0.71 to 0.92), suggesting effectiveness of cognitive group treatment
      for PTSD. PCL scores significantly improved in the 8, 10, and 12 group lengths,
      with no differences between each. Clinical improvement showed a third decreasing
      10 or more PCL points and 22% no longer meeting PTSD diagnostic criteria, with
      the best results in the 10-session group. The results suggest group-delivered
      cognitive therapy is an effective, efficient, time-limited treatment for PTSD. 

PMID- 25379267
TI  - Neurotensin agonist attenuates nicotine potentiation to cocaine sensitization.
AB  - Tobacco usage typically precedes illicit drug use in adolescent and young adult
      populations. Several animal studies suggest nicotine increases the risk for
      subsequent cocaine abuse, and may be a negative prognostic factor for treatment
      of cocaine addiction; i.e., a "gateway drug". Neurotensin (NT) is a 13-amino acid
      neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA
      neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks
      behavioral sensitization (an animal model for psychostimulant addiction) to
      nicotine, and nicotine self-administration in rats. The present study tested the
      effect of NT69L on the potentiating effects of nicotine on cocaine-induced
      locomotor sensitization. Male Wistar rats were injected daily for seven days with
      nicotine or saline (control) followed by four daily injections of cocaine. NT69L
      was administered 30 min prior to the last cocaine injection. Behavior was
      recorded with the use of activity chambers. Subchronic administration of nicotine
      enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with
      an hypothesized gateway effect. These behavioral effects of cocaine were
      attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on
      cocaine sensitization in the nicotine treated group indicated a possible
      therapeutic effect for cocaine addiction, even in the presence of enhanced
      behavioral sensitization induced by nicotine. 

PMID- 25379270
TI  - Ethnic Differences in Personality Disorder Patterns among Women Veterans
      Diagnosed with PTSD.
AB  - Personality Disorders (PDs) impair the ability to function socially and
      occupationally. PD prevalence rates among veterans who have also been diagnosed
      with posttraumatic stress disorder (PTSD) range from 45%-79%. This study examined
      ethnic differences in PDs assessed with the Millon Clinical Multiaxial Inventory
      III in 260 non-Hispanic white (64%), Hispanic (27%), and African American (9%),
      mostly single, women veterans in treatment for PTSD. After adjusting for
      covariates including number and sexual-nature of trauma, findings revealed the
      adjusted odds ratio of having a cluster A PD was almost three times higher for
      African Americans (p = 0.046) then the other two ethnic groups, which may be
      driven by the paranoid PD scale and potentially reflects an adaptive response to
      racial discrimination. In cluster designation analysis, the odds were twice as
      high of having a cluster B PD with childhood trauma (p = 0.046), and a cluster C
      PD with sexual trauma (p = 0.004), demonstrating the significance of childhood
      and sexual trauma on long-term chronic personality patterns in women veterans.
      These results highlight the importance of using instruments with demonstrated
      diagnostic validity for minority populations. 

PMID- 25379268
TI  - Novelty, stress, and biological roots in human market behavior.
AB  - Although studies examining the biological roots of human behavior have been
      conducted since the seminal work Kahneman and Tversky, crises and panics have not
      disappeared. The frequent occurrence of various types of crises has led some
      economists to the conviction that financial markets occasionally praise
      irrational judgments and that market crashes cannot be avoided a priori (Sornette
      2009; Smith 2004). From a biological point of view, human behaviors are
      essentially the same during crises accompanied by stock market crashes and during
      bubble growth when share prices exceed historic highs. During those periods, most
      market participants see something new for themselves, and this inevitably induces
      a stress response in them with accompanying changes in their endocrine profiles
      and motivations. The result is quantitative and qualitative changes in behavior
      (Zhukov 2007). An underestimation of the role of novelty as a stressor is the
      primary shortcoming of current approaches for market research. When developing a
      mathematical market model, it is necessary to account for the biologically
      determined diphasisms of human behavior in everyday low-stress conditions and in
      response to stressors. This is the only type of approach that will enable
      forecasts of market dynamics and investor behaviors under normal conditions as
      well as during bubbles and panics. 

PMID- 25379271
TI  - Insights into Intraspecies Variation in Primate Prosocial Behavior: Capuchins
      (Cebus apella) Fail to Show Prosociality on a Touchscreen Task.
AB  - Over the past decade, many researchers have used food donation tasks to test
      whether nonhuman primates show human-like patterns of prosocial behavior in
      experimental settings. Although these tasks are elegant in their simplicity,
      performance within and across species is difficult to explain under a unified
      theoretical framework. Here, we attempt to better understand variation in
      prosociality by examining the circumstances that promote and hinder the
      expression of prosocial preferences. To this end, we tested whether capuchin
      monkeys (Cebus apella)-a species that has previously demonstrated prosocial
      preferences-would behave prosocially using a novel touchscreen task. In contrast
      to previous studies, we found that capuchins as a group did not prosocially
      deliver food to a partner. Importantly however, data from control conditions
      revealed that subjects demonstrated limited understanding of the reward
      contingencies of the task. We also compared individuals' performance in the
      current study with their performance in a previously published prosociality
      study. We conclude by discussing how continuing to explore intraspecies variation
      in performance on prosocial tasks may help inform debates regarding the existence
      of other-regarding preferences in nonhuman species. 

PMID- 25379272
TI  - Cultural adaptations of prolonged exposure therapy for treatment and prevention
      of posttraumatic stress disorder in african americans.
AB  - Posttraumatic stress disorder (PTSD) is a highly disabling disorder, afflicting
      African Americans at disproportionately higher rates than the general population.
      When receiving treatment, African Americans may feel differently towards a
      European American clinician due to cultural mistrust. Furthermore, racism and
      discrimination experienced before or during the traumatic event may compound
      posttrauma reactions, impacting the severity of symptoms. Failure to adapt
      treatment approaches to encompass cultural differences and racism-related traumas
      may decrease treatment success for African American clients. Cognitive behavioral
      treatment approaches are highly effective, and Prolonged Exposure (PE) in
      particular has the most empirical support for the treatment of PTSD. This article
      discusses culturally-informed adaptations of PE that incorporates race-related
      trauma themes specific to the Black experience. These include adding more
      sessions at the front end to better establish rapport, asking directly about race
      related themes during the assessment process, and deliberately bringing to the
      forefront race-related experiences and discrimination during treatment when
      indicated. Guidelines for assessment and the development of appropriate exposures
      are provided. Case examples are presented demonstrating adaptation of PE for a
      survivor of race-related trauma and for a woman who developed internalized racism
      following a sexual assault. Both individuals experienced improvement in their
      posttrauma reactions using culturally-informed adaptations to PE. 

PMID- 25379274
TI  - Street choice logit model for visitors in shopping districts.
AB  - In this study, we propose two models for predicting people's activity. The first
      model is the pedestrian distribution prediction (or postdiction) model by
      multiple regression analysis using space syntax indices of urban fabric and
      people distribution data obtained from a field survey. The second model is a
      street choice model for visitors using multinomial logit model. We performed a
      questionnaire survey on the field to investigate the strolling routes of 46
      visitors and obtained a total of 1211 street choices in their routes. We proposed
      a utility function, sum of weighted space syntax indices, and other indices, and
      estimated the parameters for weights on the basis of maximum likelihood. These
      models consider both street networks, distance from destination, direction of the
      street choice and other spatial compositions (numbers of pedestrians, cars,
      shops, and elevation). The first model explains the characteristics of the street
      where many people tend to walk or stay. The second model explains the mechanism
      underlying the street choice of visitors and clarifies the differences in the
      weights of street choice parameters among the various attributes, such as gender,
      existence of destinations, number of people, etc. For all the attributes
      considered, the influences of DISTANCE and DIRECTION are strong. On the other
      hand, the influences of Int.V, SHOPS, CARS, ELEVATION, and WIDTH are different
      for each attribute. People with defined destinations tend to choose streets that
      "have more shops, and are wider and lower". In contrast, people with undefined
      destinations tend to choose streets of high Int.V. The choice of males is
      affected by Int.V, SHOPS, WIDTH (positive) and CARS (negative). Females prefer
      streets that have many shops, and couples tend to choose downhill streets. The
      behavior of individual persons is affected by all variables. The behavior of
      people visiting in groups is affected by SHOP and WIDTH (positive). 

PMID- 25379275
TI  - Seeing the axial line: evidence from wayfinding experiments.
AB  - Space-geometric measures are proposed to explain the location of fixations during
      wayfinding. Results from an eye tracking study based on real-world stimuli are
      analysed; the gaze bias shows that attention is paid to structural elements in
      the built environment. Three space-geometric measures are used to explain the
      data: sky area, floor area and longest line of sight. Together with the finding
      that participants choose the more connected street, a relationship is proposed
      between the individual cognitive processes that occur during wayfinding, relative
      street connectivity measured through space syntactic techniques and the spatial
      geometry of the environment. The paper adopts an egocentric approach to gain a
      greater understanding on how individuals process the axial map. 

PMID- 25379276
TI  - Walk, Look, Remember: The Influence of the Gallery's Spatial Layout on Human
      Memory for an Art Exhibition.
AB  - The spatial organisation of museums and its influence on the visitor experience
      has been the subject of numerous studies. Previous research, despite reporting
      some actual behavioural correlates, rarely had the possibility to investigate the
      cognitive processes of the art viewers. In the museum context, where spatial
      layout is one of the most powerful curatorial tools available, attention and
      memory can be measured as a means of establishing whether or not the gallery
      fulfils its function as a space for contemplating art. In this exploratory
      experiment, 32 participants split into two groups explored an experimental, non
      public exhibition and completed two unanticipated memory tests afterwards. The
      results show that some spatial characteristics of an exhibition can inhibit the
      recall of pictures and shift the focus to perceptual salience of the artworks. 

PMID- 25379277
TI  - Attitudes and defaults save lives and protect the environment jointly and
      compensatorily: understanding the behavioral efficacy of nudges and other
      structural interventions.
AB  - A better understanding of when and why nudges (e.g., defaults, visibility or
      accessibility alterations) and other structural behavior-change measures work or
      fail can help avoid subsequent surprises such as unexpected political opposition.
      In this paper, we challenge the unilateral focus on structural interventions
      which seemingly control people's behavioral decisions-as such a focus ignores the
      flipside-namely, attitudes or, as they are called in economics, preferences. We
      argue for a conceptual understanding of individual behavior that views personal
      attitudes and behavioral costs as its two separate compensatorily effective
      determinants. This classical understanding was reintroduced into attitude
      research as the Campbell paradigm. In the logic of the Campbell paradigm, a
      person's attitude becomes obvious in the face of the behavioral costs the person
      surmounts. Technically, individual attitudes reveal themselves in a set of cost
      dependent transitively ordered performances. Behavioral costs in turn reflect the
      structural boundary conditions that are relevant as obstructive and/or supportive
      environmental forces that generically affect a specific behavior. So far, our
      research on people's attitudes toward environmental protection has demonstrated
      that the Campbell paradigm-and thus its conceptual account of individual behavior
      holds true for approximately 95% of the people in a given society. 

PMID- 25379273
TI  - Elucidating the role of neurotensin in the pathophysiology and management of
      major mental disorders.
AB  - Neurotensin (NT) is a neuropeptide that is closely associated with, and is
      thought to modulate, dopaminergic and other neurotransmitter systems involved in
      the pathophysiology of various mental disorders. This review outlines data
      implicating NT in the pathophysiology and management of major mental disorders
      such as schizophrenia, drug addiction, and autism. The data suggest that NT
      receptor analogs have the potential to be used as novel therapeutic agents acting
      through modulation of neurotransmitter systems dys-regulated in these disorders. 

PMID- 25379278
TI  - Trained Quantity Abilities in Horses (Equus caballus): A Preliminary
      Investigation.
AB  - Once believed to be a human prerogative, the capacity to discriminate between
      quantities now has also been reported in several vertebrates. To date, only two
      studies investigated numerical abilities in horses (Equus caballus) but reported
      contrasting data. To assess whether horses can be trained to discriminate between
      quantities, I have set up a new experimental protocol using operant conditioning.
      One adult female was trained to discriminate between 1 and 4 (Test 1) in three
      different conditions: non-controlled continuous variables (numerical and
      continuous quantities that co-vary with number are simultaneously available), 50%
      controlled continuous variables (intermediate condition), and 100% controlled
      continuous variables (only numerical information available). The subject learned
      the discrimination in all conditions, showing the capacity to process numerical
      information. When presented with a higher numerical ratio (2 vs. 4, Test 2), the
      subject still discriminated between the quantities but its performance was
      statistically significant only in the non-controlled condition, suggesting that
      the subject used multiple cues in presence of a more difficult discrimination. On
      the whole, the results here reported encourage the use of this experimental
      protocol as a valid tool to investigate the capacity to process numerical and
      continuous quantities in horses in future research. 

PMID- 25379279
TI  - Structure of attention and the logic of visual composition.
AB  - Two groups of subjects were presented with two facade designs, one with the front
      facade of the existing Atlanta Public Library, an exercise in modern abstract
      plastic composition by the Bauhaus-trained architect Marcel Breuer, and the other
      with alteration that toned down its plasticity and enhanced simple relations of
      its parts like symmetry and repetition. The subjects were asked to recall and
      copy the facades. The results showed that while significantly more students
      recalled elements of the altered facade, the performance was equivocal for the
      facades for the copying task. However, the copying task showed the subjects
      making greater errors in reproducing elements and relations on the periphery, and
      those that reflect a reading of depth in the facades. We present an account of
      the experiment, making the case that the results show the influence of visual
      design of the facade on the way that an interested and involved viewer attends to
      it in the course of parsing and comprehending it. The broader implication of this
      point is to see the visual design of buildings not as simple means to increase
      its aesthetic value, but as a sophisticated means to lead the viewer to specific
      forms of imaginative engagement. 

PMID- 25379280
TI  - Implementing an Assessment Clinic in a Residential PTSD Program.
AB  - Creating useful treatment plans can help improve services to consumers of mental
      health services. As more evidence-based practices are implemented, deciding what
      treatment, at what time, for whom becomes an important factor in facilitating
      positive outcomes. Readiness for trauma-focused treatments for Posttraumatic
      Stress Disorder (PTSD) such as Cognitive Processing Therapy or Prolonged Exposure
      Therapy may influence whether an individual can successfully complete either
      protocol. In addition, components of adjunctive therapies such as Acceptance and
      Commitment Therapy or Dialectical Behavior Therapy may be useful in moving a
      particular patient toward readiness and successful completion of treatment.
      Psychological assessment adds valuable data to inform these types of treatment
      decisions. This paper describes the implementation of a psychological assessment
      clinic in a residential PTSD treatment setting. Barriers to implementation, use
      of the data, and Veterans' reactions to the feedback provided to them are
      included. 

PMID- 25379281
TI  - Calculating the Social Rhythm Metric (SRM) and Examining Its Use in Interpersonal
      Social Rhythm Therapy (IPSRT) in a Healthy Population Study.
AB  - In psychiatry, the social zeitgeber theory argues that social life provides
      important social cues that entrain circadian rhythms. Disturbance of these social
      cues might lead do dis-entrainment of circadian rhythms and evoke somatic
      symptoms that increase the risk of mood disorders. In preventing and treating
      patients with bipolar disorders, the Interpersonal and Social Rhythm Therapy
      (IPSRT) relies on the Social Rhythm Metric (SRM) to (re)establish patients'
      social cues and an re-entrain circadian rhythms. Since the SRM quantifies social
      rhythms that are derived from a patient's interaction with a social environment,
      this contribution (a) calculates the SRM of the social environment of a
      representative healthy population study (n = 1249), (b) evaluates the robustness
      of the SRM as a quantifier of social rhythms by matching the scores of the pilot
      study, revealing the near absence of variance across population characteristics
      and investigation months-circadian rhythms need to be entrained for every month
      and for everyone-and (c) examines its use in IPSRT by relating high SRM-scores to
      lower psychological distress (p = 0.004) and low SRM-scores to higher social and
      emotional dysfunction (p = 0.018). 

PMID- 25379282
TI  - Measuring the Changes in Aggregate Cycling Patterns between 2003 and 2012 from a
      Space Syntax Perspective.
AB  - There has been a world-wide surge of interest in cycling over the last 10 years
      of which London has seen a continuous growth in cyclists and investment in
      infrastructure that has resulted in the introduction of the Barclays Cycle
      Superhighway and Barclays Cycling Hiring Scheme. Despite the investment in
      cycling infrastructure, there has been little understanding of cycling activity
      patterns in general and the effect of spatial configuration on cycling route
      choices. This research aims at measuring the impact of cycling infrastructure and
      spatial configuration on aggregate cyclist movement over two time periods. To do
      so, this paper presents a spatial-based cyclist movement statistical model that
      regress cyclist movement flows with measure of spatial configuration, safety and
      infrastructure and urban character attributes. Using Elephant and Castle, a
      Central London location, as a case study, the authors analyze cycling movement
      data sets from 2003 and 2012 to compare the change in cycling behaviour and the
      impact that the Cycling Superhighway 07, introduced in 2011, has had on cycling
      patterns. Findings confirm the growth of cycling in London with a 1000% increase
      in cyclists along some routes in comparison to a 10% increase in population at
      the same time. More importantly, results also suggest that higher cyclist
      movement were observed along routes with greater convenience and continuity-over
      and above route segregation from vehicular traffic. The relationship between
      spatial configuration and aggregate cyclists movement is consistent between 2003
      and 2012 where spatial configuration have remained the same while changes were
      observed in both modal split and cycling infrastructure. This result is in line
      with previous research wherein aggregate higher cyclists movement are observed on
      major routes offering direct connections than less direct routes. From a spatial
      cognition perspective, this research enriches our understanding on how the
      external built environment as measured by the spatial configuration measure
      relates to aggregated cyclists movement overtime and in identifying key potential
      factors in influencing cyclist wayfinding. Further research is needed into
      validating the results and examining this relationship at an individual basis on
      route choice. These results help us better understand the trade off between
      cycling safety and cycling legibility which could help inform cycling route
      design in the future. 

PMID- 25379283
TI  - Working memory training in schizophrenia and healthy populations.
AB  - Cognitive deficits are consistently demonstrated in individuals with
      schizophrenia. Cognitive training involves structured exercises prescribed and
      undertaken with the intention of enhancing cognitive abilities such as attention,
      memory, and problem solving. Thus, cognitive training represents a potentially
      promising intervention for enhancing cognitive abilities in schizophrenia.
      However, cognitive training programs are numerous and heterogeneous, hence, the
      generalizability of training related outcomes can be challenging to assess. This
      article will provide a brief overview of current literature on cognitive training
      and explore how knowledge of working memory training in healthy populations can
      potentially be applied to enhance cognitive functioning of individuals with
      schizophrenia. 

PMID- 25379284
TI  - Latino Veterans with PTSD: A Systematic Review.
AB  - Latinos have a long history of military service with recent service including
      combat conditions and multiple deployments, which are highly associated with
      posttraumatic stress disorder (PTSD). Clinical acumen underscores the importance
      of culture in assessment and treatment, but there has been little scientific
      literature that investigates the unique needs of veteran Latinos with PTSD. The
      primary goal of this systematic review was to analyze the existing literature on
      Latino veterans with PTSD and to critically evaluate attention to cultural
      issues. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      were used to guide this review. Peer-reviewed, research reports written in
      English on Latino Veterans with PTSD since 1980 were included; 20 were assessment
      related, and nine were treatment related. All studies were quantitative. Only 13
      studies mentioned culture as part of the context for Latino veterans, and only
      seven included cultural factors as part of the study design. Present findings
      highlight a lack of research focused on understanding cultural factors related to
      the assessment and treatment of Latino veterans with PTSD. Culturally-informed
      research on Latino veterans from current wars, Latina veterans and Latino veteran
      treatment outcomes are necessary to provide culturally-appropriate care to this
      growing veteran subgroup. 

PMID- 25379285
TI  - Amino Acid compositions of 27 food fishes and their importance in clinical
      nutrition.
AB  - Proteins and amino acids are important biomolecules which regulate key metabolic
      pathways and serve as precursors for synthesis of biologically important
      substances; moreover, amino acids are building blocks of proteins. Fish is an
      important dietary source of quality animal proteins and amino acids and play
      important role in human nutrition. In the present investigation, crude protein
      content and amino acid compositions of important food fishes from different
      habitats have been studied. Crude protein content was determined by Kjeldahl
      method and amino acid composition was analyzed by high performance liquid
      chromatography and information on 27 food fishes was generated. The analysis
      showed that the cold water species are rich in lysine and aspartic acid, marine
      fishes in leucine, small indigenous fishes in histidine, and the carps and
      catfishes in glutamic acid and glycine. The enriched nutrition knowledge base
      would enhance the utility of fish as a source of quality animal proteins and
      amino acids and aid in their inclusion in dietary counseling and patient guidance
      for specific nutritional needs. 

PMID- 25379286
TI  - Synthesis, characterization, and biological evaluation of some new functionalized
      terphenyl derivatives.
AB  - New functionalized terphenyl derivatives incorporating various heterocyclic rings
      are prepared by using 4,4''-difluoro-5'-hydroxy-1,1':3',1''-terphenyl-4'
      carbohydrazide as a key intermediate derived from 4,4'-difluoro chalcone, a
      versatile synthone. All the derivatives are characterized by (1)H NMR, IR, and
      mass spectral data. All the synthesized products are screened for their in vitro
      antimicrobial and antioxidant properties. The majority of the tested compounds
      exhibited significant antioxidant activity and some of them showed good
      antimicrobial activity. 

PMID- 25379287
TI  - A DFT and semiempirical model-based study of opioid receptor affinity and
      selectivity in a group of molecules with a morphine structural core.
AB  - We report the results of a search for model-based relationships between mu,
      delta, and kappa opioid receptor binding affinity and molecular structure for a
      group of molecules having in common a morphine structural core. The wave
      functions and local reactivity indices were obtained at the ZINDO/1 and B3LYP/6
      31G(**) levels of theory for comparison. New developments in the expression for
      the drug-receptor interaction energy expression allowed several local atomic
      reactivity indices to be included, such as local electronic chemical potential,
      local hardness, and local electrophilicity. These indices, together with a new
      proposal for the ordering of the independent variables, were incorporated in the
      statistical study. We found and discussed several statistically significant
      relationships for mu, delta, and kappa opioid receptor binding affinity at both
      levels of theory. Some of the new local reactivity indices incorporated in the
      theory appear in several equations for the first time in the history of model
      based equations. Interaction pharmacophores were generated for mu, delta, and
      kappa receptors. We discuss possible differences regulating binding and
      selectivity in opioid receptor subtypes. This study, contrarily to the
      statistically backed ones, is able to provide a microscopic insight of the
      mechanisms involved in the binding process. 

PMID- 25379288
TI  - Secondary Structural Preferences of Some Antibacterial Cyclooctapeptides in the
      Presence of Calcium(II).
AB  - The purpose of this study is to understand the interactions of some antibacterial
      cationic amphipathic cyclooctapeptides with calcium(II) and their secondary
      structural preferences. The thermodynamic parameters associated with calcium(II)
      interactions, between the antibacterial active cyclooctapeptides (COP 1-6) and
      those that did not exhibit significant activities (COP 7-9), were studied by
      isothermal titration calorimetry. Calcium(II) binding in the absence and presence
      of micellar dodecylphosphocholine (DPC), a membrane mimicking detergent, was
      conducted by circular dichroism (CD). Both groups of cyclopeptides showed weak
      binding affinities for calcium(II) (Kb ca. 10(-3) M(-1)). However, CD data showed
      that the antimicrobial peptides COP 1-6 adopted a twisted beta-sheet structure
      (positive CD absorption band at ca. 203 nm) in the presence of calcium(II) in
      micellar DPC. In contrast, COP 7-9, which lacked antibacterial activity, adopted
      a different conformational structure (negative CD absorption band at ca. 203 nm).
      These results indicate that these cyclopeptides could adopt secondary structural
      preferences in the presence of calcium(II) amidst a hydrophobic environment to
      elicit their antibacterial activity. These findings could be useful in
      facilitating the design of cyclopeptide derivatives that can adopt this beta
      sheet-like secondary structure and, thereby, provide a useful molecular template
      for crafting antibacterial compounds. 

PMID- 25379290
TI  - Estimation of Anti-HIV Activity of HEPT Analogues Using MLR, ANN, and SVM
      Techniques.
AB  - The present study deals with the estimation of the anti-HIV activity (log1/C) of
      a large set of 107 HEPT analogues using molecular descriptors which are
      responsible for the anti-HIV activity. The study has been undertaken by three
      techniques MLR, ANN, and SVM. The MLR model fits the train set with R (2)=0.856
      while in ANN and SVM with higher values of R (2) = 0.850, 0.874, respectively.
      SVM model shows improvement to estimate the anti-HIV activity of trained data,
      while in test set ANN have higher R (2) value than those of MLR and SVM
      techniques. R m (2) = metrics and ridge regression analysis indicated that the
      proposed four-variable model MATS5e, RDF080u, T(O?O), and MATS5m as correlating
      descriptors is the best for estimating the anti-HIV activity (log 1/C) present
      set of compounds. 

PMID- 25379289
TI  - Recent pharmacological developments on rhodanines and 2,4-thiazolidinediones.
AB  - Thiazolidines are five-member heterocyclic having sulfur, nitrogen, and oxygen
      atoms in their ring structure and exhibiting potent as well as wide range of
      pharmacological activities. In this minireview, recent updates on synthesis and
      pharmacological evaluations of molecules based on 2,4-thiazolidine and rhodanine
      are discussed. 

PMID- 25379291
TI  - Synthesis and evaluation of some novel chromone based dithiazoles as
      antimicrobial agents.
AB  - Novel substituted 1,2,4-dithiazolylchromones 3a-j were synthesized by the
      reaction of 3-formylchromones (1a-j) with two equivalents of p
      chlorothiobenzamide (2) in dry xylene and characterized spectroscopically (IR,
      (1)H and (13)C NMR, mass) and elemental analysis. All synthesized compounds were
      screened for in vitro antimicrobial activity against various pathogenic bacterial
      and fungal strains and were found to possess good to moderate inhibitory
      potential against all tested strains. Antimicrobial results reveal that compounds
      bearing lipophilic electron withdrawing groups such as chloro and bromo displayed
      significant inhibitory potential against both bacterial and fungal strains.
      Particularly, compound 3c displayed significant inhibitory against bacterial
      strains and compound 3h exhibits significant inhibitory potential in comparison
      to standard drug fluconazole against fungal strain S. cerevisiae. 

PMID- 25379292
TI  - Synthesis and in vitro cytotoxic activity of chromenopyridones.
AB  - Novel substituted chromenopyridones (3a-j and 6a-d) were synthesized and
      evaluated in vitro for the cytotoxic activity against various human cancer cell
      lines such as prostate (PC-3), breast (MCF-7), CNS (IMR-32), cervix (Hela), and
      liver (Hep-G2). preliminary cytotoxic screening showed that all the compounds
      possess a good to moderate inhibitory activity against various cancer cell lines.
      Particularly, compound 6b bearing allyl moiety displayed a significant cytotoxic
      potential in comparison to standard drugs. 

PMID- 25379293
TI  - Novel Antimicrobial Agents: Fluorinated 2-(3-(Benzofuran-2-yl) pyrazol-1
      yl)thiazoles.
AB  - A new series of 2-pyrazolin-1-ylthiazoles 8a-d and 13-16 was synthesized by
      cyclization of N-thiocarboxamide-2-pyrazoline with different haloketones and 2,3
      dichloroquinoxaline. The structures of the new compounds were confirmed by
      elemental analyses as well as NMR, IR, and mass spectral data. The newly
      synthesized compounds were evaluated for their antimicrobial activities, and also
      their minimum inhibitory concentration (MIC) against most of test organisms was
      performed. Amongst the tested ones, compound 8c displayed excellent antimicrobial
      activity. 

PMID- 25379294
TI  - Modified anchor shaped post core design for primary anterior teeth.
AB  - Restoring severely damaged primary anterior teeth is challenging to pedodontist.
      Many materials are tried as a post core but each one of them has its own
      drawbacks. This a case report describing a technique to restore severely damaged
      primary anterior teeth with a modified anchor shaped post. This technique is not
      only simple and inexpensive but also produces better retention. 

PMID- 25379295
TI  - Severe periodontal disease associated with long-term treatment with intravenous
      immunoglobulin.
AB  - Intravenous immunoglobulin (IVIG) is used in the treatment of neuropathy. This
      case report presents, for the first time, a patient with severe periodontal
      destruction after chronic therapy with IVIG. The patient reported having
      extracted his maxillary anterior teeth himself due to high mobility. Clinical
      examination and radiographic images show a generalized and severe periodontitis.
      No significant alterations in genetic or microbiological features were observed.
      The present case suggests that periodontal disease aggravation could be
      considered a new adverse effect of IVIG therapy. Postulated mechanisms are immune
      complexes formation, complement activation, and a direct effect in osteoclasts.
      In conclusion, it is important that patients that will receive IVIG treatment
      underwent dental evaluation. 

PMID- 25379296
TI  - Granulomatous cheilitis: successful treatment of two recalcitrant cases with
      combination drug therapy.
AB  - Granulomatous cheilitis is a rare, idiopathic, inflammatory disorder which
      usually affects young adults. It is characterized by persistent, diffuse,
      nontender, soft-to-firm swelling of one or both lips. Various treatment
      modalities have been suggested. In spite of the best treatment, recurrence of the
      disease is very common. We report two cases of granulomatous cheilitis treated
      with a combination of steroids, metronidazole, and minocycline with no signs of
      relapse at one-year follow-up. 

PMID- 25379297
TI  - Atypical Association of Angelman Syndrome and Klinefelter Syndrome in a Boy with
      47,XXY Karyotype and Deletion 15q11.2-q13.
AB  - Angelman syndrome (AS, OMIM 105830) is a neurogenetic disorder with firm clinical
      diagnostic guidelines, characterized by severe developmental delay and speech
      impairment, balanced and behavioral disturbance as well as microcephaly,
      seizures, and a characteristic electroencephalogram (EEG). The majority of AS
      cases (70%) are caused by a 15q11.2-q13 deletion on the maternally derived
      chromosome. The frequency of AS has been estimated to be between 1/10000 and
      1/20000. Klinefelter syndrome (KS) occurs due to the presence of an extra X
      chromosome (karyotype 47,XXY). The main features in KS are small testes,
      hypergonadotropic hypogonadism, gynecomastia, learning difficulties, and
      infertility. We present what is, to our knowledge, the first case of a patient
      with both KS and AS due to a 15q11.2-q13 deletion on the maternally derived
      chromosome and an extra X chromosome of paternal origin. He showed dysmorphic
      features, axial hypotonia, and delayed acquisition of motor skills. Early
      diagnosis is essential for optimal treatment of AS children; this is one of the
      earliest diagnosed cases of AS probably due to the presence of two syndromes.
      Clinical findings in this patient here described may be helpful to identify any
      other cases and to evaluate recurrence risks in these families. 

PMID- 25379298
TI  - Hepatic artery mycotic aneurysm associated with staphylococcal endocarditis with
      successful treatment: case report with review of the literature.
AB  - Mycotic hepatic artery aneurysm is a vascular pathology associated with bacterial
      endocarditis. It is rare in occurrence after the introduction of effective
      antibiotics. We present a young patient with injection drug abuse associated
      staphylococcal endocarditis which was successfully treated with antibiotics and
      valve replacement who presented with abdominal pain. He was found to have mycotic
      aneurysm of hepatic artery which was successfully treated with coil embolization.

PMID- 25379299
TI  - Epithelioid angiomyolipoma of liver with an inflammatory component: a case
      report.
AB  - Angiomyolipomas (AMLs) are benign mesenchymal tumors seen in kidneys in
      association with tuberous sclerosis. They are uncommon in liver. Angiomyolipomas
      of liver show great histological diversity and various types and patterns are
      described. Among them, epithelioid and inflammatory angiomyolipomas are rare. We
      report a case of epithelioid angiomyolipoma of Liver with an inflammatory
      component. 

PMID- 25379300
TI  - Severe starvation-induced hepatocyte autophagy as a cause of acute liver injury
      in anorexia nervosa: a case report.
AB  - Introduction. Mild elevation of transaminase may be observed in anorexia nervosa,
      but acute liver injury is uncommon. A complex programmed cell death in response
      to starvation, called autophagy, has been described in experimental and human
      studies. Case Presentation. A 24-year-old woman suffering from anorexia nervosa
      was hospitalized for severe malnutrition. At admission, there were biological
      signs of acute liver injury but no electrolytic imbalance. After having ruled out
      the most common causes of liver injury, the patient was carefully refed. As liver
      tests remained abnormal, liver biopsy was performed. At histology and electron
      microscopy, numerous signs suggestive of starvation-induced hepatocyte autophagy
      were found. Discussion. Severe starvation can be associated with acute liver
      injury that is slowly reversible with careful enteral nutrition. In this clinical
      situation, profound hepatic glycogen depletion in association with autophagy
      appears as the leading cause of liver injury. 

PMID- 25379301
TI  - Granulomatous hepatitis secondary to histoplasma infection after treatment with
      infliximab.
AB  - Classical presentation of Histoplasma infection includes fever and respiratory
      symptoms. Opportunistic microorganisms must be suspected on immunocompromised
      patients who develop bizarre symptoms. We present a case of a female patient with
      rheumatoid arthritis who received treatment with Infliximab during one and a half
      year; she developed granulomatous hepatitis secondary to Histoplasma infection.
      The patient was admitted with acute hepatitis and thrombocytopenic coagulopathy.
      A liver biopsy was performed revealing granulomatous hepatitis, microvesicular
      steatosis, isolated apoptotic cells, and parenchyma microabscesses. PAS and
      Gomori stains revealed areas with mycotic microorganisms morphologically
      compatible with Histoplasma spp. and confirmed by culture. 

PMID- 25379302
TI  - Transjugular Retrograde Obliteration prior to Liver Resection for Hepatocellular
      Carcinoma Associated with Hyperammonemia due to Spontaneous Portosystemic Shunt.
AB  - A 67-year-old woman had hepatocellular carcinoma (HCC) measuring 3.7 cm at S8 of
      the liver with hyperammonemia due to a spontaneous giant mesocaval shunt.
      Admission laboratory data revealed albumin, 2.9 g/dL; total bilirubin, 1.3 mg/dL;
      plasma ammonia level (NH3), 152 g/dL; total bile acid (TBA) 108.5 MUmoL/L;
      indocyanine green retention rate at 15 min (ICG15), 63%. Superior mesenteric
      arterial portography revealed a hepatofugal giant mesocaval shunt, and the portal
      vein was not visualized. Before surgery, transjugular retrograde obliteration
      (TJO) for the mesocaval shunt was attempted to normalize the portal blood flow.
      Via the right internal jugular vein, a 6 F occlusive balloon catheter was
      inserted superselectively into the mesocaval shunt. The mesocaval shunt was
      successfully embolized using absolute ethanol and a 50% glucose solution. Eleven
      days after TJO, NH3, TBA, and ICG15 decreased to 56, 44, and 33, respectively.
      Superior mesenteric arterial portography after TJO revealed a hepatopetal portal
      flow. Partial hepatectomy of S8 was performed 25 days after TJO. The subsequent
      clinical course showed no complications, and the woman was discharged on
      postoperative day 14. We conclude that the combined therapy of surgery and TJO is
      an effective means of treating HCC with hyperammonemia due to a spontaneous
      portosystemic shunt. 

PMID- 25379303
TI  - A girl with autoimmune cytopenias, nonmalignant lymphadenopathy, and recurrent
      infections.
AB  - We describe a girl, now 9 years of age, with chronic idiopathic thrombocytopenic
      purpura, persistent nonmalignant lymphadenopathy, splenomegaly, recurrent
      infections, and autoimmune hemolytic anemia. Her symptoms partly fit the
      definitions of both autoimmune lymphoproliferative syndrome (ALPS) and common
      variable immunodeficiency disorders (CVIDs). Genetic analysis showed no
      abnormalities in the ALPS-genes FAS, FASLG, and CASP10. The CVID-associated TACI
      gene showed a homozygous polymorphism (Pro251Leu), which is found also in healthy
      controls. 

PMID- 25379304
TI  - Effective treatment of rheumatoid arthritis-associated interstitial lung disease
      by B-cell targeted therapy with rituximab.
AB  - Rheumatoid arthritis- (RA-) associated interstitial lung disease (RA-ILD) is the
      extra-articular complication with most adverse impact on the quality of life and
      survival in RA patients. However, treatment options are limited and controlled
      studies are lacking. Here, we present the case of a 66-year-old patient suffering
      from severe RA-ILD, which has been successfully treated with Rituximab (RTX).
      After failure of conventional DMARD therapy, our patient showed sustained
      improvement of clinical pulmonary parameters as well as joint inflammation
      following B-cell depletion with RTX. The six-minute-walk test improved from 380
      meters to 536 meters and the forced vital capacity from 2.49 liters to 3.49. The
      disease activity score could be reduced from 7.7 to 2.8. Therefore, RTX might be
      considered as an alternative treatment for RA-ILD in patients not responding to
      conventional DMARD therapy. 

PMID- 25379305
TI  - Angora wool asthma in textile industry.
AB  - Up to now the exposures to hair and skin derivatives of animals have not yet been
      the subject of systematic studies. The observation of a clinical case has
      provided the opportunity for a review of the literature. The inpatient was a 49
      year-old man, a carder in a textile factory, exposed to angora wool. He noticed
      the appearance of dyspnea during working hours. There was no eosinophilia in
      blood, and the results of pulmonary function tests were normal. The nonspecific
      bronchial provocation test with methacholine demonstrated an abnormal bronchial
      reactivity. The challenge test with angora wool was positive (decrease in FEV1 of
      more than 40%) as well as total IGE and specific IgE to rabbit epithelium (433
      KU/l and 12.1 KUA/l, resp.). Several sources of allergens were found in the
      rabbit, and the main allergen was represented by proteins from epithelia, urine,
      and saliva. Most of these proteins belong to the family of lipocalin, they
      function as carriers for small hydrophobic molecules (vitamins and pheromones).
      If the diagnosis of occupational asthma caused by animal hair and skin
      derivatives may be relatively easy by means of the challenge test, defining
      etiology is complicated because of the lack of in vitro tests. 

PMID- 25379306
TI  - Visceral leishmaniasis or systemic lupus erythematosus flare?
AB  - Systemic lupus erythematosus (SLE) is a multisystem disorder characterised by B
      cell hyperactivity with production of multiple autoantibodies. Fever in SLE may
      be caused by disease exacerbation or by infection. We report a patient of SLE
      that was later complicated by fever, pancytopenia, and massive splenomegaly.
      Corticosteroid therapy for SLE might have masked the underlying infection at
      earlier stage. Despite negative results of rk-39 test and bone marrow biopsy, a
      very high suspicion for visceral leishmaniasis (VL) led us to go for direct
      agglutination test (DAT) and polymerase chain reaction (PCR) for leishmanial
      antigen that revealed positive results. Moreover, significant improvement in
      clinical and biochemical parameters was noted on starting the patient on
      antileishmanial therapy. 

PMID- 25379307
TI  - Autoimmune hepatitis with anti centromere antibodies.
AB  - We present the case report of a 49-year-old type 2 diabetes mellitus patient
      presenting with abdominal pain and black stool for 15 days. A proper workup of
      laboratory investigations helped us diagnose autoimmune hepatitis with
      anticentromere antibodies. The authors would like to highlight that screening AIH
      patients for anticentromere antibody is not mandatory but can be considered,
      especially in the presence of disease-related symptomatology for quicker, more
      accurate diagnosis and optimum management. 

PMID- 25379308
TI  - Chronic granulomatous disease presenting as aseptic ascites in a 2-year-old
      child.
AB  - Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency syndrome
      that results from abnormal nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase function. This defect leads to recurrent catalase-positive bacterial and
      fungal infections as well as associated granuloma formation. We review the case
      of a 2-year-old boy who presented with ascites and fever of an unknown origin as
      manifestations of CGD. Cultures were negative for infection throughout his
      course, and CGD was suspected after identification of granulomas on peritoneal
      biopsy. Genetic testing revealed a novel mutation in the CYBB gene underlying his
      condition. This paper highlights the importance of considering CGD in the
      differential diagnosis of fever of unknown origin and ascites in children. 

PMID- 25379309
TI  - Recurrent Skin and Lung Infections in Autosomal Dominant Hyper IgE Syndrome with
      Transactivation Domain STAT3 Mutation.
AB  - Background. Hyper IgE is a rare systemic disease characterized by the clinical
      triad of high serum levels of IgE (>2000 IU/mL), eczema, and recurrent
      staphylococcal skin and lung infections. The presentation of hyper IgE syndrome
      is highly variable, which makes it easy to confuse the diagnosis with that of
      severe atopy or other rare immunodeficiency disorders. Case Report. A 23-year-old
      Hispanic presented with history of frequent respiratory and gastrointestinal
      infections as a child and multiple episodes of skin and lung infections (abscess)
      with Staphylococcus aureus throughout his adult life. He had multiple eczematous
      lesions and folliculitis over his entire body, oral/esophageal candidiasis, and
      retention of his primary teeth. The IgE was elevated (>5000 IU/mL). Genetic
      mutation analysis revealed a mutation affecting the transactivation domain of the
      STAT3 gene. Conclusion. The hallmark of hyper IgE syndrome is serum IgE of >2000
      IU/mL. Hyper IgE syndrome is a genetic disorder that is either autosomal dominant
      or recessive. A definite diagnosis can be made with genetic mutation analysis,
      and in this case, it revealed a very rare finding of the transactivation domain
      STAT3 mutation. Hyper IgE syndrome is a challenge for clinicians in establishing
      a diagnosis in suspected cases. 

PMID- 25379311
TI  - Infectious and noninfectious granulomatosis in patient with multiple sclerosis:
      diagnostic dilemmas and followup.
AB  - Patient was followed up over the course of 30 years. In 1978, after severe
      systemic infection followed by fever, pulmonary edema, and numerous neurological
      manifestations, patient was differentially diagnosed with apoplectic form of
      multiple sclerosis (MS), which was confirmed a year later via neurological and
      MRI findings. Approximately 20 years following the initial attack, sarcoidosis
      was diagnosed during the regular preoperative procedures required for cataract
      surgery. As consequence of lower immune system, infectious granulomatosis in form
      of pulmonary tuberculosis developed. Ophthalmological findings revealed bilateral
      retrobulbar neuritis (RBN) approximately six years after initial attack. This
      developed into total uveitis with retinal periphlebitis and anterior
      granulomatous uveitis-all of which are clinically similar in both MS and
      sarcoidosis. 

PMID- 25379310
TI  - Increased IL-17, a Pathogenic Link between Hepatosplenic Schistosomiasis and
      Amyotrophic Lateral Sclerosis: A Hypothesis.
AB  - The immune system protects the organism from foreign invaders and foreign
      substances and is involved in physiological functions that range from tissue
      repair to neurocognition. However, an excessive or dysregulated immune response
      can cause immunopathology and disease. A 39-year-old man was affected by severe
      hepatosplenic schistosomiasis mansoni and by amyotrophic lateral sclerosis. One
      question that arose was, whether there was a relation between the parasitic and
      the neurodegenerative disease. IL-17, a proinflammatory cytokine, is produced
      mainly by T helper-17 CD4 cells, a recently discovered new lineage of effector
      CD4 T cells. Experimental mouse models of schistosomiasis have shown that IL-17
      is a key player in the immunopathology of schistosomiasis. There are also reports
      that suggest that IL-17 might have an important role in the pathogenesis of
      amyotrophic lateral sclerosis. It is hypothesized that the factors that might
      have led to increased IL-17 in the hepatosplenic schistosomiasis mansoni might
      also have contributed to the development of amyotrophic lateral sclerosis in the
      described patient. A multitude of environmental factors, including infections,
      xenobiotic substances, intestinal microbiota, and vitamin D deficiency, that are
      able to induce a proinflammatory immune response polarization, might favor the
      development of amyotrophic lateral sclerosis in predisposed individuals. 

PMID- 25379312
TI  - Bilateral lung transplantation in a patient with humoral immune deficiency: a
      case report with review of the literature.
AB  - Humoral immune deficiencies have been associated with noninfectious disease
      complications including autoimmune cytopenias and pulmonary disease. Herein we
      present a patient who underwent splenectomy for autoimmune cytopenias and
      subsequently was diagnosed with humoral immune deficiency in the context of
      recurrent infections. Immunoglobulin analysis prior to initiation of intravenous
      immunoglobulin (IVIG) therapy was notable for low age-matched serum levels of IgA
      (11 mg/dL), IgG2 (14 mg/L), and IgG4 (5 mg/L) with a preserved total level of
      IgG. Flow cytometry was remarkable for B cell maturation arrest at the IgM+/IgD+
      stage. Selective screening for known primary immune deficiency-causing genetic
      defects was negative. The disease course was uniquely complicated by the
      development of pulmonary arteriovenous malformations (AVMs), ultimately requiring
      bilateral lung transplantation in 2012. This is a patient with humoral immune
      deficiency that became apparent only after splenectomy, which argues for routine
      immunologic evaluation prior to vaccination and splenectomy. Lung transplantation
      is a rare therapeutic endpoint and to our knowledge has never before been
      described in a patient with humoral immune deficiency for the indication of
      pulmonary AVMs. 

PMID- 25379313
TI  - New Onset Refractory Status Epilepticus in a Young Man with H1N1 Infection.
AB  - Objective. To report a case of refractory status epilepticus (SE) as an unusual
      early manifestation of H1N1 influenza infection. Introduction. H1N1 neurological
      complications have been reported and consist mainly of seizures or encephalopathy
      occurring in children. However, we only found a single report of an adult
      developing complex partial SE with H1N1 infection. Case Report. A 21-year-old
      previously healthy man was brought to the emergency room (ER) after a witnessed
      generalized tonic clonic seizure (GTCS). He was fully alert and afebrile upon ER
      arrival, but a second GTCS prompted treatment with Lorazepam and Fosphenytoin.
      The initial EEG showed diffuse slowing, but a repeat one requested as the patient
      failed to regain consciousness revealed recurrent focal seizures of independent
      bihemispheric origin, fulfilling the criteria for nonconvulsive SE. Chest X-ray,
      followed by chest CT scan, showed a left upper lobe consolidation. H1N1 infection
      was confirmed with PCR on bronchoalveolar lavage material. Despite aggressive
      treatment with Midazolam, Propofol, and multiple high dose antiepileptic drugs,
      the electrographic seizures recurred at every attempt to reduce the intravenous
      sedative drugs. The patient died two weeks after his initial presentation.
      Conclusion. H1N1 should be added to the list of rare causes of refractory SE,
      regardless of the patient's age. 

PMID- 25379314
TI  - Postpartum prolapsed leiomyoma with uterine inversion managed by vaginal
      hysterectomy.
AB  - Background. Uterine inversion is a rare, but life threatening, obstetrical
      emergency which occurs when the uterine fundus collapses into the endometrial
      cavity. Various conservative and surgical therapies have been outlined in the
      literature for the management of uterine inversions. Case. We present a case of a
      chronic, recurrent uterine inversion, which was diagnosed following spontaneous
      vaginal delivery and recurred seven weeks later. The uterine inversion was likely
      due to a leiomyoma. This late-presenting, chronic, recurring uterine inversion
      was treated with a vaginal hysterectomy. Conclusion. Uterine inversions can occur
      in both acute and chronic phases. Persistent vaginal bleeding with the appearance
      of a prolapsing fibroid should prompt further investigation for uterine inversion
      and may require surgical therapy. A vaginal hysterectomy may be an appropriate
      management option in select populations and may be considered in women who do not
      desire to maintain reproductive function. 

PMID- 25379315
TI  - Serious delayed hair toe tourniquet syndrome with bone erosion and flexor tendon
      lesion.
AB  - Hair toe tourniquet syndrome (HTTS) is an uncommon pediatric condition occurring
      when the toe is circumferentially strangulated by human hair or fibers. An 8-week
      old little girl was admitted to the Emergency Department because of the worsening
      swelling in the right second and third toes, which had been been previously
      treated with a local antibiotic thinking of an infection. An unrecognized HTTS
      was leading the third toe to necrosis. An urgent release of the constricting band
      on the two toes was performed and bone erosion and partial flexor tendon lesion
      on the third toe were detected. We would like to raise awareness in the community
      and in colleagues about HTTS in children, because early recognition and urgent
      treatment are mandatory to provide an adequate management and prevent severe
      complications. 

PMID- 25379316
TI  - A case of priapism with risperidone.
AB  - Priapism is a urologic emergency defined as a prolonged, possibly painful, penile
      erection. There are several known causes of priapism including psychotropic
      medications. One of the mechanisms by which antipsychotics are believed to induce
      priapism is through alpha-1 antagonism. This is case of a 50-year-old male with a
      history of schizophrenia with previous priapism related to trazodone, who
      presents with new onset priapism associated with risperidone. In this case, the
      treatment of priapism includes discontinuation of the offending agent and
      drainage of the corpus cavernosum twice along with intracavernosal phenylephrine
      injections. It is important to educate patients on priapism as a possible side
      effect of medications. It is also important to consider previous episodes of
      medication-induced priapism when prescribing psychotropic medications as this may
      increase the patient's future risk of priapism. 

PMID- 25379317
TI  - Acute hemorrhagic myositis in inflammatory myopathy and review of the literature.
AB  - We describe two patients with dermatomyositis that presented with interstitial
      lung disease, positive V and Shawl sign who developed acute spontaneous
      abdominal/retroperitoneal bleed. Both patients expired despite aggressive
      treatment and resuscitation. Hemorrhagic myositis in these two patients with
      inflammatory myopathy is a very rare complication. The association of anti-Ro52
      with this potentially very serious complication remains unclear. This potential
      relationship should be further evaluated in future studies. 

PMID- 25379318
TI  - Multidimensional sternal fixation to overcome a "floating" sternum.
AB  - This case report describes the repair of a complete sternal dehiscence of the
      lower right sternum using sternal wires, manubrial plates, and a Talon closure
      device for rigid, multidimensional sternal fixation. Sternal dehiscence is a rare
      but significant cause of morbidity for patients undergoing median sternotomy. The
      risk factors for this complication are well described and although sternal wires
      have traditionally been used for primary closure, rigid fixation with sternal
      plates is a viable alternative to avoid dehiscence in this high-risk cohort. 

PMID- 25379319
TI  - Inflammatory pseudotumor containing necrotizing granulomatous lesions of kidney:
      a hitherto undescribed entity.
AB  - Herein reported is a case of inflammatory pseudotumor (IPT) of kidney. It is not
      described in WHO, AFIP, and other books. A review of the literature revealed
      about 35 cases. A 76-year-old man underwent nephrectomy under clinical diagnosis
      of renal pelvic carcinoma. Grossly, a solid tumor was seen in renal parenchyma.
      Microscopically, it was composed of spindle cell tissue with inflammation and
      many necrotizing granulomas. Epithelioid histiocytes were abundant but giant
      cells were few. Lymphocytes and plasma cells were also seen. The features
      suggested tuberculosis (TB), but Ziehl-Neelsen stains and PCR revealed no TB
      bacillus. Immunohistochemistry showed that the tumor spindle cells were positive
      for vimentin, CD68, CD45, and Ki-67 (labeling = 18%), alpha-smooth muscle
      antigen, and NSE. Focal staining of KIT (mast cells), S100 protein (Langerhans
      cells), and CD10 (spindle cells) was present. IgG4 was negative. The tumor
      spindle cells were negative for other antigens examined. 

PMID- 25379320
TI  - Short course high dose radiotherapy in the treatment of anaplastic thyroid
      carcinoma.
AB  - Purpose. Anaplastic thyroid carcinoma (ATC) is a rare but aggressive tumor with
      limited survival. To date, the ideal radiation treatment schedule, one that
      balances limited survival with treatment efficacy, remains undefined. In this
      retrospective series we investigate the effectiveness and tolerability of
      hypofractionated radiation therapy in the treatment of ATC. Methods. 17 patients
      with biopsy proven ATC treated between 2004 and 2012 were reviewed for outcomes
      and toxicity. All patients received short course radiation. Results. The most
      commonly prescribed dose was 54 Gy in 18 fractions. Median survival was 9.3
      months. 47% of patients were metastatic at diagnosis and the majority of patients
      (88%) went on to develop metastasis. Death from local progression was seen in 3
      patients (18%), 41% experienced grade 3 toxicity, and there were no grade 4
      toxicities. Conclusions. Here we demonstrated the safety and feasibility of
      hypofractionated radiotherapy in the treatment of ATC. This approach offers
      shorter treatment courses (3-4 weeks) compared to traditional fractionation
      schedules (6-7 weeks), comparable toxicity, local control, and the ability to
      transition to palliative care sooner. Local control was dependent on the degree
      of surgical debulking, even in the metastatic setting. 

PMID- 25379321
TI  - Poststroke outcomes.

PMID- 25379322
TI  - Fertility Desires and Intentions and the Relationship to Consistent Condom Use
      and Provider Communication Regarding Childbearing Among HIV Clients in Uganda.
AB  - OBJECTIVES: HIV prevention and reproductive health programs emphasize consistent
      condom use and preventing unplanned pregnancies, but do not account for the
      childbearing desires of many HIV clients. We examined the correlates of fertility
      desires and intentions, including condom use, among HIV clients in Uganda.
      METHODS: Baseline data from a prospective cohort study of clients starting
      antiretroviral therapy were analyzed. All measures were self-report, except
      abstracted CD4 count. RESULTS: The sample included 767 clients; 34% were men and
      50% had a primary sex partner. Among those with a desire (31%) or intention (24%)
      for having a child in the near future, 60% had not discussed this with providers.
      A majority (61%) had received advise about family planning, and 27% were told by
      their provider that they should not bear a child because of their HIV status. In
      regression analysis, male gender, younger age, higher CD4, having fewer children,
      and having a primary partner were significantly associated with fertility desires
      and intentions; having been told by one's provider not to have a child was
      associated with intentions but not desires. Among participants with a primary
      partner, consistent condom use was greater among those with no fertility
      intentions, as was receipt of advise about family planning, while HIV disclosure
      to partner was greater among those with intentions. Partner HIV status was not
      associated with fertility desires or intentions. CONCLUSIONS: These findings
      highlight the need for HIV care and reproductive health programs to incorporate
      safer conception counseling and improve provider/patient communication regarding
      childbearing.

PMID- 25379324
TI  - An Analysis of Trainers' Perspectives within an Ecological Framework: Factors
      that Influence Mine Safety Training Processes.
AB  - BACKGROUND: Satisfactory completion of mine safety training is a prerequisite for
      being hired and for continued employment in the coal industry. Although training
      includes content to develop skills in a variety of mineworker competencies,
      research and recommendations continue to specify that specific limitations in the
      self-escape portion of training still exist and that mineworkers need to be
      better prepared to respond to emergencies that could occur in their mine.
      Ecological models are often used to inform the development of health promotion
      programs but have not been widely applied to occupational health and safety
      training programs. METHODS: Nine mine safety trainers participated in in-depth
      semi-structured interviews. A theoretical analysis of the interviews was
      completed via an ecological lens. Each level of the social ecological model was
      used to examine factors that could be addressed both during and after mine safety
      training. RESULTS: The analysis suggests that problems surrounding communication
      and collaboration, leadership development, and responsibility and accountability
      at different levels within the mining industry contribute to deficiencies in
      mineworkers' mastery and maintenance of skills. CONCLUSION: This study offers a
      new technique to identify limitations in safety training systems and processes.
      The analysis suggests that training should be developed and disseminated with
      consideration of various levels-individual, interpersonal, organizational, and
      community-to promote skills. If factors identified within and between levels are
      addressed, it may be easier to sustain mineworker competencies that are
      established during safety training.

PMID- 25379323
TI  - Sex-specific Profiles of Blood Metal Levels Associated with Metal-Iron
      Interactions.
AB  - The mechanisms by which iron is absorbed are similar to those of divalent metals,
      particularly manganese, lead, and cadmium. These metals, however, show different
      toxicokinetics in relation to menarche or menopause, although their interaction
      with iron is the same. This review focuses on the kinetics of these three toxic
      metals (manganese, lead, and cadmium) in relation to menarche, pregnancy, and
      menopause. The iron-manganese interaction is the major factor determining sex
      specific differences in blood manganese levels throughout the whole life cycle.
      The effects of estrogen overshadow the association between iron deficiency and
      increased blood lead concentrations, explaining why women, despite having lower
      ferritin concentrations, have lower blood lead concentrations than men. Iron
      deficiency is associated with elevated cadmium levels in premenopausal women, but
      not in postmenopausal women or men; these findings indicate that sex-specific
      differences in cadmium levels at older ages are not due to iron-cadmium
      interactions, and that further studies are required to identify the source of
      these differences. In summary, the potential causes of sex-specific differences
      in the blood levels of manganese, lead, and cadmium differ from each other,
      although all these three metals are associated with iron deficiency. Therefore,
      other factors such as estrogen effects, or absorption rate as well as iron
      deficiency, should be considered when addressing environmental exposure to toxic
      metals and sex-specific differences in the blood levels of these metals. 

PMID- 25379325
TI  - Framework for continuous assessment and improvement of occupational health and
      safety issues in construction companies.
AB  - BACKGROUND: Construction industry is among the most hazardous industries, and
      needs a comprehensive and simple-to-administer tool to continuously assess and
      promote its health and safety performance. METHODS: Through the study of various
      standard systems (mainly Health, Safety, and Environment Management System;
      Occupational Health and Safety Assessment Series 180001; and British Standard,
      occupational health and safety management systems-Guide 8800), seven main
      elements were determined for the desired framework, and then, by reviewing
      literature, factors affecting these main elements were determined. The relative
      importance of each element and its related factors was calculated at
      organizational and project levels. The provided framework was then implemented in
      three construction companies, and results were compared together. RESULTS: THE
      RESULTS OF THE STUDY SHOW THAT THE RELATIVE IMPORTANCE OF THE MAIN ELEMENTS AND
      THEIR RELATED FACTORS DIFFER BETWEEN ORGANIZATIONAL AND PROJECT LEVELS:
      leadership and commitment are the most important elements at the organization
      level, whereas risk assessment and management are most important at the project
      level. CONCLUSION: The present study demonstrated that the framework is easy to
      administer, and by interpreting the results, the main factors leading to the
      present condition of companies can be determined.

PMID- 25379326
TI  - Incidence and Predictors of Hand-Arm Musculoskeletal Complaints among Vibration
      exposed African Cassava and Corn Millers.
AB  - BACKGROUND: Cassava and corn milling is a growing small-scale enterprise in
      Africa. We aimed to determine the incidence of hand-arm musculoskeletal
      complaints among vibration-exposed Congolese cassava and corn millers in the
      previous 12 months. METHODS: A cross-sectional study was conducted, prior to a
      follow-up study, from March to May 2013 among cassava/corn millers in Lubumbashi,
      Democratic Republic of Congo, in which 365 millers age-matched to 365 civil
      workers anonymously answered a questionnaire. RESULTS: Overall incidence of hand
      arm musculoskeletal complaints was 25.8% in millers (vs. 5.2% in civil workers; p
      < 0.001). The risk of experiencing musculoskeletal symptoms was seven times
      higher in millers [vs. civil workers; odds ratio (OR) = 7.10; 95% confidence
      interval (CI): 4.03-12.50; p < 0.0001]; 2.4 times higher in smoking millers (vs.
      smoking civil office workers; OR = 2.36; 95% CI: 1.42-3.88; p < 0.001); 3.6 times
      higher in millers with longer daily exposure (> 8 hours; vs. those working <= 8
      hours; OR = 3.56; 95% CI: 1.93-3.61; p = 0.026); and 7.4 times higher in young
      millers (vs. older millers, OR = 7.39; 95% CI: 1.29-75.52; p < 0.001). Smoking,
      number of cigarettes, and daily exposure duration were positively correlated with
      musculoskeletal complaints. CONCLUSION: This study revealed a relatively high
      incidence of musculoskeletal complaints among African cassava and corn millers.
      The use of anti-vibration protective equipment and the regulation of this
      hazardous occupation may reduce the burden of musculoskeletal disorders in
      millers.

PMID- 25379327
TI  - Oral health of stone mine workers of jodhpur city, rajasthan, India.
AB  - BACKGROUND: Occupational injuries cause major health problems, which the
      developed, developing, and underdeveloped nations worldwide are facing today. The
      present study aimed to assess dental caries, periodontal health of stone mine
      workers, and the relationship between wasting diseases and the years of working
      experience. METHODS: The study population comprised 510 men, selected based on
      the stratified cluster sampling procedure. Clinical oral examinations were
      carried out, and periodontal disease, dental caries, and wasting diseases were
      recorded. RESULTS: Workers were in the age group of 17-56 years; the prevalence
      of dental caries in the workers was found to be 74%, with a mean decayed,
      missing, filled teeth index of 2.89. A periodontal pocket of more than 6 mm was
      observed in 6% of the workers. CONCLUSION: The oral health of mine workers is in
      a poor state; steps should be taken so as to provide basic medical and dental
      care facilities.

PMID- 25379328
TI  - Knowledge and Experiences of Risks among Pupils in Vocational Education.
AB  - BACKGROUND: Young male and female workers are over-represented in statistics
      concerning negative outcomes of poor work environment and risky work. Young
      workers often have low awareness of risk, a lack of safety training, and
      inadequate introduction to the work. The aim of this study was to identify the
      knowledge and experiences of pupils of vocational schools concerning potential
      work environment risks in their future work. METHODS: The study design was a dual
      one, and included a questionnaire and focus group interviews. The study group
      consisted of 239 pupils from 10 upper secondary schools, who were graduating
      pupils in four vocational programs: the Industrial Technology Programme, the
      Restaurant Management and Food Programme, the Transport Programme, and the
      Handicraft Programme (in which students specialize in wood products). The upper
      secondary schools were located in the central region of Sweden. RESULTS: The
      pupils had limited knowledge that employers must, by law, conduct risk analyses
      and prevent risks. Many felt that they themselves are mainly responsible for
      performing their tasks safely. Pupils in all programs mentioned acute risk as the
      greatest risk at work. The theoretical education about safety at work was
      provided in the 1(st) year of the 3-year vocational programs. CONCLUSION: A
      systematic approach to pupils' training in work environment, which is a basis for
      a safe and healthy workplace, is lacking. The study findings indicate that pupils
      are offered knowledge far from that intended by laws and by state-of-the-art
      occupational health risk research.

PMID- 25379329
TI  - Nonfatal occupational injuries in norwegian farmers.
AB  - BACKGROUND: Agriculture ranks among the most dangerous trades worldwide. There
      is, however, still a lack of knowledge on nonfatal injuries in agriculture. The
      aim of this study was to describe the nature and occurrence of nonfatal injuries
      in farmers in two counties in central Norway. METHODS: A questionnaire was sent
      to 7,004 farmers in Norway. We asked for information about the respondents and
      the farm, whether the farmer had had work-related injuries on the farm during the
      past 12 months, and details about the incidence and seriousness of the injury.
      RESULTS: A total of 2,699 respondents gave a response rate of 42%. Of the
      respondents, 249 (9.2%) reported one or more work-related injuries. The most
      usual cause of injury involved an animal, and >75% of these happened inside the
      outbuilding. Among these, 17.5% had a consequence of sick leave or a more serious
      result. When all the accidents were analyzed by stepwise logistic regression,
      only the variables: works alone, has >3,500 stipulated working hours at the farm,
      and the type of production were statistical significant explanatory variables for
      having an injury. CONCLUSION: Incorporating safety aspects to a greater extend in
      the design and construction of outbuildings would make a substantial contribution
      to injury prevention in agriculture.

PMID- 25379331
TI  - Analysis of Two Electrocution Accidents in Greece that Occurred due to Unexpected
      Re-energization of Power Lines.
AB  - Investigation and analysis of accidents are critical elements of safety
      management. The over-riding purpose of an organization in carrying out an
      accident investigation is to prevent similar accidents, as well as seek a general
      improvement in the management of health and safety. Hundreds of workers have
      suffered injuries while installing, maintaining, or servicing machinery and
      equipment due to sudden re-energization of power lines. This study presents and
      analyzes two electrical accidents (1 fatal injury and 1 serious injury) that
      occurred because the power supply was reconnected inadvertently or by mistake. 

PMID- 25379330
TI  - Burnout and workload among health care workers: the moderating role of job
      control.
AB  - BACKGROUND: As health care workers face a wide range of psychosocial stressors,
      they are at a high risk of developing burnout syndrome, which in turn may affect
      hospital outcomes such as the quality and safety of provided care. The purpose of
      the present study was to investigate the moderating effect of job control on the
      relationship between workload and burnout. METHODS: A total of 352 hospital
      workers from five Italian public hospitals completed a self-administered
      questionnaire that was used to measure exhaustion, cynicism, job control, and
      workload. Data were collected in 2013. RESULTS: In contrast to previous studies,
      the results of this study supported the moderation effect of job control on the
      relationship between workload and exhaustion. Furthermore, the results found
      support for the sequential link from exhaustion to cynicism. CONCLUSION: This
      study showed the importance for hospital managers to carry out management
      practices that promote job control and provide employees with job resources, in
      order to reduce the burnout risk.

PMID- 25379332
TI  - Accuracy of Body Mass Index-defined Obesity Status in US Firefighters.
AB  - Obesity is a significant problem affecting United States (US) firefighters. While
      body mass index (BMI) is widely used to diagnose obesity, its use for this
      occupational group has raised concerns about validity. We examined rates and
      types of misclassification of BMI-based obesity status compared to body fat
      percentage (BF%) and waist circumference (WC). Male career firefighters (N = 994)
      from 20 US departments completed all three body composition assessments. Mean
      BMI, BF%, and WC were 29 kg/m(2), 23%, and 97 cm, respectively. Approximately 33%
      and 15% of BF%- and WC-defined obese participants were misclassified as non-obese
      (false negatives) using BMI, while 8% and 9% of non-obese participants defined by
      BF% and WC standards were identified as obese (false positives) using BMI. When
      stratified by race/ethnicity, Pacific Islanders showed high rates of false
      positive misclassification. Precision in obesity classification would be improved
      by using WC along with BMI to determine firefighters' weight status. 

PMID- 25379333
TI  - Developing a Best-Evidence Pre-employment Medical Examination: An Example from
      the Construction Industry.
AB  - The Dutch construction industry has introduced a compulsory preemployment medical
      examination (PE-ME). Best-evidence contents related to specific job demands are,
      however, lacking and need to be gathered. After the identification of job demands
      and health problems in the construction industry (systematic literature search
      and expert meeting), specific job demands and related requirements were defined
      and instruments proposed. Finally, a work ability assessment was linked to the
      instruments' outcomes, resulting in the modular character of the developed PE-ME.
      Twenty-two specific job demands for all Dutch construction jobs were identified,
      including kneeling/squatting, working under time pressure, and exposure to
      hazardous substances. The next step was proposing self-report questions,
      screening questionnaires, clinical tests, and/or performance-based tests, leading
      to a work ability judgment. "Lifting/carrying" is described as an example. The
      new modular PE-ME enables a job-specific assessment of work ability to be made
      for more than 100 jobs in the Dutch construction industry. 

PMID- 25379334
TI  - Species-level assessment of secondary metabolite diversity among Hamigera species
      and a taxonomic note on the genus.
AB  - Secondary metabolite phenotypes in nine species of the Hamigera clade were
      analysed to assess their correlations to a multi-gene species-level phylogeny.
      High-pressure-liquid-chromatography-based chemical analysis revealed three
      distinctive patterns of secondary metabolite production: (1) the nine species
      could be divided into two groups on the basis of production of the sesquiterpene
      tricinonoic acid; (2) the tricinonoic acid-producing group produced two cyclic
      peptides avellanins A and B; (3) the tricinonoic acid-non-producing group could
      be further divided into two groups according to the production of avellanins A
      and B. The chemical phenotype was consistent with the phylogeny of the species,
      although metabolite patterns were not diagnostic at the species level. In
      addition, the taxonomy of the Hamigera clade was updated with the new combination
      Hamigera ingelheimensis proposed for Merimbla ingelheimensis, so that all species
      in the clade are now in the same genus.

PMID- 25379335
TI  - Sporothriolide derivatives as chemotaxonomic markers for Hypoxylon monticulosum.
AB  - During the course of a screening for novel anti-infective agents from cultures of
      tropical Xylariaceae originating from French Guiana and Thailand, pronounced
      antifungal activity was noted in extracts of cultures of Hypoxylon monticulosum.
      A bioassay-guided fractionation led to the known metabolite sporothriolide as
      active principle. In addition, three new derivatives of sporothriolide were
      isolated, for which we propose the trivial names sporothric acid, isosporothric
      acid and dihydroisosporothric acid. Their chemical structures were elucidated by
      high-resolution electrospray mass spectrometry in conjunction with two
      dimensional nuclear magnetic resonance (2D-NMR) spectroscopy. From earlier
      studies on the biogenesis of the chemically similar canadensolides, we postulate
      that the new compounds were shunt products, rather than biogenetic precursors of
      sporothriolide. Interestingly, this compound class, as well as strong antifungal
      activities, was only observed in multiple cultures of H. monticulosum, but not in
      several hundreds of Hypoxylon cultures studied previously or concurrently.
      Therefore, sporothriolide production may constitute a species-specific feature
      with respect to Hypoxylon and the Xylariaceae, although the compound was
      previously reported from non-related fungal taxa.

PMID- 25379336
TI  - Bioactive natural products from fungicolous Hawaiian isolates: secondary
      metabolites from a Phialemoniopsis sp.
AB  - Chemical investigations of two fungal isolates initially identified as members of
      the genus Phialemonium are described. Both isolates were obtained as colonists of
      other fungi collected on the island of Hawaii and were later assigned as P.
      curvatum. However, P. curvatum has recently been reclassified as a member of a
      new genus (Phialemoniopsis) and renamed as Phialemoniopsis curvata. Studies of
      solid-substrate fermentation cultures of one of these isolates afforded an
      oxirapentyn analogue and destruxin A4 as major components, while analysis of the
      second strain led to the isolation of several simple aromatic metabolites and a
      compound of mixed biogenetic origin called gabusectin that had previously been
      reported only in a patent. Structures were assigned mainly by detailed nuclear
      magnetic resonance and mass spectrometry analysis, and those of two of the major
      components were confirmed by X-ray crystallography. This report constitutes the
      first description of secondary metabolites from a member of the genus
      Phialemoniopsis.

PMID- 25379337
TI  - Sea foam as a source of fungal inoculum for the isolation of biologically active
      natural products.
AB  - Due to a rate increase in the resistance of microbial pathogens to currently used
      antibiotics, there is a need in society for the discovery of novel
      antimicrobials. Historically, fungi are a proven source for antimicrobial
      compounds. The main goals of this study were to investigate the fungal diversity
      associated with sea foam collected around the coast of Prince Edward Island and
      the utility of this resource for the production of antimicrobial natural
      products. Obtained isolates were identified using ITS and nLSU rDNA sequences,
      fermented on four media, extracted and fractions enriched in secondary
      metabolites were screened for antimicrobial activity. The majority of the
      isolates obtained were ascomycetes, consisting of four recognized marine taxa
      along with other ubiquitous genera and many 'unknown' isolates that could not be
      identified to the species level using rDNA gene sequences. Secondary metabolite
      isolation efforts lead to the purification of the metabolites epolones A and B,
      pycnidione and coniothyrione from a strain of Neosetophoma samarorum; brefeldin
      A, leptosin J and the metabolite TMC-264 from an unknown fungus (probably
      representative of an Edenia sp.); and 1-hydroxy-6-methyl-8-hydroxymethylxanthone,
      chrysophanol and chrysophanol bianthrone from a Phaeospheria spartinae isolate.
      The biological activity of each of these metabolites was assessed against a panel
      of microbial pathogens as well as several cell lines.

PMID- 25379338
TI  - An assessment of natural product discovery from marine (sensu strictu) and marine
      derived fungi.
AB  - The natural products community has been investigating secondary metabolites from
      marine fungi for several decades, but when one attempts to search for validated
      reports of new natural products from marine fungi, one encounters a literature
      saturated with reports from 'marine-derived' fungi. Of the 1000+ metabolites that
      have been characterized to date, only approximately 80 of these have been
      isolated from species from exclusively marine lineages. These metabolites are
      summarized here along with the lifestyle and habitats of their producing
      organisms. Furthermore, we address some of the reasons for the apparent
      disconnect between the stated objectives of discovering new chemistry from marine
      organisms and the apparent neglect of the truly exceptional obligate marine
      fungi. We also offer suggestions on how to reinvigorate enthusiasm for marine
      natural products discovery from fungi from exclusive marine lineages and
      highlight the need for critically assessing the role of apparently terrestrial
      fungi in the marine environment.

PMID- 25379339
TI  - Lipopolysaccharide (LPS) stimulation of fungal secondary metabolism.
AB  - We report on a preliminary investigation of the use the Gram-negative bacterial
      cell wall constituent lipopolysaccharide (LPS) as a natural chemical cue to
      stimulate and alter the expression of fungal secondary metabolism. Integrated
      high-throughput micro-cultivation and micro-analysis methods determined that 6 of
      40 (15%) of fungi tested responded to an optimal exposure to LPS (0.6 ng/mL) by
      activating, enhancing or accelerating secondary metabolite production. To explore
      the possible mechanisms behind this effect, we employed light and fluorescent
      microscopy in conjunction with a nitric oxide (NO)-sensitive fluorescent dye and
      an NO scavenger to provide evidence that LPS stimulation of fungal secondary
      metabolism coincided with LPS activation of NO. Several case studies demonstrated
      that LPS stimulation can be scaled from single microplate well (1.5 mL) to
      preparative (>400 mL) scale cultures. For example, LPS treatment of Penicillium
      sp. (ACM-4616) enhanced pseurotin A and activated pseurotin A1 and pseurotin A2
      biosynthesis, whereas LPS treatment of Aspergillus sp. (CMB-M81F) substantially
      accelerated and enhanced the biosynthesis of shornephine A and a series of
      biosynthetically related ardeemins and activated production of neoasterriquinone.
      As an indication of broader potential, we provide evidence that cultures of
      Penicillium sp. (CMB-TF0411), Aspergillus niger (ACM-4993F), Rhizopus oryzae (ACM
      165F) and Thanatephorus cucumeris (ACM-194F) were responsive to LPS stimulation,
      the latter two examples being particular noteworthy as neither are known to
      produce secondary metabolites. Our results encourage the view that LPS
      stimulation can be used as a valuable tool to expand the molecular discovery
      potential of fungal strains that either have been exhaustively studied by or are
      unresponsive to traditional culture methodology.

PMID- 25379340
TI  - Assessing the effects of adsorptive polymeric resin additions on fungal secondary
      metabolite chemical diversity.
AB  - Adsorptive polymeric resins have been occasionally described to enhance the
      production of specific secondary metabolites (SMs) of interest. Methods that
      induce the expression of new chemical entities in fungal fermentations may lead
      to the discovery of new bioactive molecules and should be addressed as possible
      tools for the creation of new microbial chemical libraries for drug lead
      discovery. Herein, we apply both biological activity and chemical evaluations to
      assess the use of adsorptive resins as tools for the differential expression of
      SMs in fungal strain sets. Data automation approaches were applied to ultra high
      performance liquid chromatography analysis of extracts to evaluate the general
      influence in generating new chemical entities or in changing the production of
      specific SMs by fungi grown in the presence of resins and different base media.

PMID- 25379341
TI  - A genome-wide survey of the secondary metabolite biosynthesis genes in the wheat
      pathogen Parastagonospora nodorum.
AB  - The model pathogen Parastagonospora nodorum is a necrotroph and the causal agent
      of the wheat disease Septoria nodorum blotch (SNB). The sequenced P. nodorum
      genome has revealed that the fungus harbours a large number of secondary
      metabolite genes. Secondary metabolites are known to play important roles in the
      virulence of plant pathogens, but limited knowledge is available about the SM
      repertoire of this wheat pathogen. Here, we review the secondary metabolites that
      have been isolated from P. nodorum and related species of the same genus and
      provide an in-depth genome-wide overview of the secondary metabolite gene
      clusters encoded in the P. nodorum genome. The secondary metabolite gene survey
      reveals that P. nodorum is capable of producing a diverse range of small
      molecules and exciting prospects exist for discovery of novel virulence factors
      and bioactive molecules.

PMID- 25379342
TI  - Heterologous fermentation of a diterpene from Alternaria brassisicola.
AB  - A variety of different applications render terpenes and terpenoids attractive
      research targets. A promising but so far insufficiently explored family of
      terpenoids are the fusicoccanes that comprise a characteristic 5-8-5 fused
      tricyclic ring system. Besides herbicidal effects, these compounds also show
      apoptotic and anti-tumour effects on mammalian cells. The access to fusicoccanes
      from natural sources is scarce. Recently, we introduced a metabolically
      engineered Saccharomyces cerevisiae strain to enable the heterologous
      fermentation of the shared fusicoccane-diterpenoid precursor, fusicocca-2,10(14)
      diene. Here, we show experiments towards the identification of bottlenecks in
      this process. The suppression of biosynthetic by-products via medium optimisation
      was found to be an important aspect. In addition, the fermentation process seems
      to be improved under oxygen limitation conditions. Under fed-batch conditions,
      the fermentation yield was reproducibly increased to approximately 20 mg/L.
      Furthermore, the impact of the properties of the terpene synthase on the
      fermentation yield is discussed, and the preliminary studies on the engineering
      of this key enzyme are presented.

PMID- 25379343
TI  - [Microvascular decompresion for trigeminal neuralgia, report of 36 cases and
      literature review].
AB  - BACKGROUND: The aim of this study is to describe the results of 36 patients with
      trigeminal neuralgia treated with microvascular decompression. METHODS: Between
      June 2005 and May 2012, 36 patients with trigeminal neuralgia were operated by
      the first author (AC), underwent microvascular decompression. The age, sex,
      duration of symptoms before surgery, and surgical finds, were all evaluated. In
      addition, postoperative results were also analyzed. RESULTS: Twenty-five patients
      were women and 11 were men. The average age of the patients was 48 years. The
      average time of postoperative follow-up after the surgery was 36 months. Relief
      from pain until now occurred in 32 patients (88%). Pain recurrence was observed
      in 4 patients; of those, 2 cases showed a vein compression. CONCLUSION: The
      microvascular decompression for trigeminal neuralgia is a safe an effective
      option. A vein compression could point out an unfavorable follow-up.

PMID- 25379344
TI  - Regulatory barriers surrounding the use of whole slide imaging in the United
      States of America.

PMID- 25379345
TI  - American Telemedicine Association clinical guidelines for telepathology.

PMID- 25379346
TI  - A nuclear circularity-based classifier for diagnostic distinction of desmoplastic
      from spindle cell melanoma in digitized histological images.
AB  - CONTEXT: Distinction of spindle cell melanoma (SM) and desmoplastic melanoma (DM)
      is clinically important due to differences in metastatic rate and prognosis;
      however, histological distinction is not always straightforward. During a routine
      review of cases, we noted differences in nuclear circularity between SM and DM.
      AIM: The primary aim in our study was to determine whether these differences in
      nuclear circularity, when assessed using a basic ImageJ-based threshold
      extraction, can serve as a diagnostic classifier to distinguish DM from SM.
      SETTINGS AND DESIGN: Our retrospective analysis of an established patient cohort
      (SM n = 9, DM n = 9) was employed to determine discriminatory power. SUBJECTS AND
      METHODS: Regions of interest (total n = 108; 6 images per case) were selected
      from scanned H and E-stained histological sections, and nuclear circularity was
      extracted and quantified by computational image analysis using open source tools
      (plugins for ImageJ). STATISTICAL ANALYSIS: Using analysis of variance, t-tests,
      and Fisher's exact tests, we compared extracted quantitative shape measures;
      statistical significance was defined as P < 0.05. RESULTS: Classifying
      circularity values into four shape categories (spindled, elongated, oval, round)
      demonstrated significant differences in the spindled and round categories.
      Paradoxically, DM contained more spindled nuclei than SM (P = 0.011) and SM
      contained more round nuclei than DM (P = 0.026). Performance assessment using a
      combined shape-classification of the round and spindled fractions showed 88.9%
      accuracy and a Youden index of 0.77. CONCLUSIONS: Spindle cell melanoma and DM
      differ significantly in their nuclear morphology with respect to fractions of
      round and spindled nuclei. Our study demonstrates that quantifying nuclear
      circularity can be used as an adjunct diagnostic tool for distinction of DM and
      SM.

PMID- 25379347
TI  - Web-based oil immersion whole slide imaging increases efficiency and clinical
      team satisfaction in hematopathology tumor board.
AB  - BACKGROUND: Whole slide imaging (WSI) is widely used for education and research,
      but is increasingly being used to streamline clinical workflow. We present our
      experience with regard to satisfaction and time utilization using oil immersion
      WSI for presentation of blood/marrow aspirate smears, core biopsies, and tissue
      sections in hematology/oncology tumor board/treatment planning conferences (TPC).
      METHODS: Lymph nodes and bone marrow core biopsies were scanned at *20
      magnification and blood/marrow smears at 83X under oil immersion and uploaded to
      an online library with areas of interest to be displayed annotated digitally via
      web browser. Pathologist time required to prepare slides for scanning was
      compared to that required to prepare for microscope projection (MP). Time
      required to present cases during TPC was also compared. A 10-point evaluation
      survey was used to assess clinician satisfaction with each presentation method.
      RESULTS: There was no significant difference in hematopathologist preparation
      time between WSI and MP. However, presentation time was significantly less for
      WSI compared to MP as selection and annotation of slides was done prior to TPC
      with WSI, enabling more efficient use of TPC presentation time. Survey results
      showed a significant increase in satisfaction by clinical attendees with regard
      to image quality, efficiency of presentation of pertinent findings, aid in
      clinical decision-making, and overall satisfaction regarding pathology
      presentation. A majority of respondents also noted decreased motion sickness with
      WSI. CONCLUSIONS: Whole slide imaging, particularly with the ability to use oil
      scanning, provides higher quality images compared to MP and significantly
      increases clinician satisfaction. WSI streamlines preparation for TPC by
      permitting prior slide selection, resulting in greater efficiency during TPC
      presentation.

PMID- 25379348
TI  - The rare sprengel deformity: our experience with three cases.
AB  - Sprengel shoulder is a rare congenital deformity of one or both scapulae that is
      usually detected at birth. It occurs due to failure of the scapula to descend
      during intrauterine development and its cause is still unknown. Although the
      deformity appears randomly most of the time, familial cases have been reported.
      Sprengel shoulder is often associated with Klippel-Feil syndrome and other
      congenital skeletal deformities. Anteroposterior X-ray imaging can accurately
      diagnose Sprengel deformity. However, computed tomography and magnetic resonance
      scans with three-dimensional reconstruction are nowadays used in everyday
      practice in order to diagnose concomitant abnormalities, study in detail the
      anatomy of the affected shoulder(s), and plan appropriate management. We present
      here our imaging experience from three pediatric cases with Sprengel shoulder and
      take the opportunity to discuss this rare entity, which is, nevertheless, the
      commonest congenital defect of the scapula. 

PMID- 25379349
TI  - Pelvic pheochromocytoma mimicking as urinary bladder pheochromocytoma: looking
      beyond the obvious.
AB  - Pheochromocytomas located outside the adrenal glands are called paragangliomas. A
      pelvic location is rare, the most common location for a paraganglioma being the
      retroperitoneal space. Paragangliomas arise from neural crest cells. Pelvic
      pheochromocytomas may mimic urinary bladder pheochromocytomas on imaging studies.
      Patients may present with hypertensive crisis during micturition. We present a 26
      year-old female who presented to us with accelerated hypertension with episodes
      of severe headache and palpitation during micturition. Based on imaging studies,
      she was diagnosed to have a urinary bladder pheochromocytoma. However, on
      exploration, the patient was found to have an extravesical pheochromocytoma
      arising from the left posterolateral pelvic wall, which was excised while
      preserving the bladder. We present this case report as pelvic pheochromocytomas
      can mimic bladder pheochromocytomas and are difficult to differentiate on
      radiological imaging and can lead to inadvertent cystectomy. 

PMID- 25379350
TI  - Ewing's Sarcoma of the Finger.
AB  - Ewing's sarcoma is a mesenchymal cell tumor usually seen in long bones but very
      rarely seen in the bones of a finger. Swelling and pain are the most common
      complaints of the affected finger. In radiological imaging, it may be seen as
      permeative bone destruction accompanied by a soft tissue component or an
      expansile bone lesion. A 27-year-old right-hand dominant female patient presented
      with a swelling on the proximal phalanx of her right 3(rd) finger that had
      existed for 3 years. However, the mass started to gradually increase in size and
      the pain worsened over a period of 5 weeks. The mass was excised under regional
      intravenous anesthesia and Ewing's sarcoma was confirmed following a
      histopathological evaluation. No local recurrence or metastasis was detected 1
      year after surgery. Since Ewing's sarcoma is rarely seen in the finger, we
      present this case with its radiological and clinical findings. 

PMID- 25379351
TI  - MDCT Venography Evaluation of a Rare Collateral Vein Draining from the Left
      Subclavian Vein to the Great Cardiac Vein.
AB  - Congenital vascular anomalies of the venous drainage in the chest affect both
      cardiac and non-cardiac structures. Collateral venous drainage from the left
      subclavian vein to the great cardiac vein is a rare venous drainage pattern.
      These anomalies present a diagnostic challenge. Multi-detector computed
      tomography (MDCT) is useful in the diagnosis and treatment planning of these
      clinically complex disorders. We present a case report of an 18-year-old
      Caucasian male who came to our institute for evaluation of venous drainage
      patterns to the heart. We describe the contrast technique of bilateral dual
      injection MDCT venography and the imaging features of the venous drainage
      patterns to the heart. 

PMID- 25379352
TI  - Hermansky-pudlak syndrome complicated by pulmonary fibrosis: radiologic
      pathologic correlation and review of pulmonary complications.
AB  - Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder
      characterized by oculocutaneous hypopigmentation, platelet dysfunction, and in
      many cases, life-threatening pulmonary fibrosis. We report the clinical course,
      imaging, and postmortem findings of a 38-year-old female with HPS-related
      progressive pulmonary fibrosis, highlighting the role of imaging in assessment of
      disease severity and prognosis. 

PMID- 25379353
TI  - Unusual unilateral fracture of the condylar and coronoid processes of the
      mandible.
AB  - The incidence of condylar fracture is very high and most are not caused by direct
      trauma. On the other hand, fracture of the coronoid process is reported less
      often than fracture of other parts of the mandible. We report a case of right
      subcondylar and coronoid fractures without any evidence of direct trauma to the
      zygomatic area or an indirect trauma to the mandibular corpus or sypmheseal
      region. The possible cause was identified as acute reflex contraction of the
      temporalis muscles leading to coronoid and condylar stress fractures. 

PMID- 25379354
TI  - Diagnostic imaging for dental implant therapy.
AB  - Dental implant is a device made of alloplastic (foreign) material implanted into
      the jaw bone beneath the mucosal layer to support a fixed or removable dental
      prosthesis. Dental implants are gaining immense popularity and wide acceptance
      because they not only replace lost teeth but also provide permanent restorations
      that do not interfere with oral function or speech or compromise the self-esteem
      of a patient. Appropriate treatment planning for replacement of lost teeth is
      required and imaging plays a pivotal role to ensure a satisfactory outcome. The
      development of pre-surgical imaging techniques and surgical templates helps the
      dentist place the implants with relative ease. This article focuses on various
      types of imaging modalities that have a pivotal role in implant therapy. 

PMID- 25379356
TI  - Predicting Birth-Related Levator Ani Tear Severity in Primiparous Women:
      Evaluating Maternal Recovery from Labor and Delivery (EMRLD Study).
AB  - OBJECTIVE: To determine which maternal characteristics or birth events
      independently predict severity of levator ani muscle (LA) tears at first vaginal
      birth in a longitudinal/observational investigation in a tertiary care hospital.
      SAMPLE: Ninety primiparas with at least one at risk for LA tear inclusion factor
      at vaginal birth: maternal age >= 33 years, second stage >= 150 minutes,
      macrosomia, instrumented delivery, and/or anal sphincter laceration were studied.
      METHODS: Magnetic Resonance Imaging (MRI) was obtained early postpartum (mean +/-
      sd 48.9 +/- 21.6 days) to identify LA tear. Severity of LA muscle fiber loss was
      graded on an ordinal scale of: "0" as no loss, "1" as <50% unilateral loss, "2"
      as >=50% unilateral or <50% bilateral loss, and "3" as >=50% bilateral loss. Data
      were analyzed using proportional odds modeling. Inclusion factors were explored
      as predictors of LA tear severity and at analysis episiotomy, time spent actively
      pushing, epidural, and oxytocin were also considered. The main outcome measures
      of interest included grading of severity of LA muscle fiber loss on an ordinal
      scale. RESULTS: Respective counts/percentages of women within each 0 thru 3
      ordered category of LA tear severity were: "0" = 58(64%), "1" = 9(10%), "2" =
      15(17%), and "3" = 8(9%). Estimates and 95% CI for significant demographic or
      obstetric univariate predictors of LA tear severity level were age, OR 1.093 (CI
      1.012 - 1.180), p = 0.023; and time spent in active pushing, OR 1.089 (CI 1.005 -
      1.180), p = 0.038. The other factors considered were not significant. There were
      too few women with forceps deliveries to analyze. CONCLUSION: In our enriched
      sample of primiparous women, 26% showed a significant LA tear. Maternal age and
      time spent actively pushing independently predict LA tear severity.

PMID- 25379355
TI  - Roles of c-FLIP in Apoptosis, Necroptosis, and Autophagy.
AB  - Cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein (c-FLIP)
      is a major antiapoptotic protein and an important cytokine and chemotherapy
      resistance factor that suppresses cytokine- and chemotherapy-induced apoptosis. c
      FLIP is expressed as long (c-FLIPL), short (c-FLIPS), and c-FLIPR splice variants
      in human cells. c-FLIP binds to FADD and/or caspase-8 or -10 and TRAIL receptor 5
      (DR5). This interaction in turn prevents Death-Inducing Signaling Complex (DISC)
      formation and subsequent activation of the caspase cascade. c-FLIPL and c-FLIPS
      are also known to have multifunctional roles in various signaling pathways, as
      well as activating and/or upregulating several cytoprotective and pro-survival
      signaling proteins including Akt, ERK, and NF-kappaB. In addition to its role in
      apoptosis, c-FLIP is involved in programmed necroptosis (necrosis) and autophagy.
      Necroptosis is regulated by the Ripoptosome, which is a signaling intracellular
      cell death platform complex. The Ripoptosome contains receptor-interacting
      protein-1/Receptor-Interacting Protein-3 (RIP1), caspase-8, caspase-10, FADD, and
      c-FLIP isoforms involved in switching apoptotic and necroptotic cell death. c
      FLIP regulates the Ripoptosome; in addition to its role in apoptosis, it is
      therefore also involved in necrosis. c-FLIPL attenuates autophagy by direct
      acting on the autophagy machinery by competing with Atg3 binding to LC3, thereby
      decreasing LC3 processing and inhibiting autophagosome formation. Upregulation of
      c-FLIP has been found in various tumor types, and its silencing has been shown to
      restore apoptosis triggered by cytokines and various chemotherapeutic agents.
      Hence, c-FLIP is an important target for cancer therapy. This review focuses on
      (1) the anti-apoptotic role of c-FLIP splice variants in preventing apoptosis and
      inducing cytokine and chemotherapy drug resistance, as well as its roles in
      necrosis and autophagy, and (2) modulation of c-FLIP expression as a means to
      enhance apoptosis and modulate necrosis and autophagy in cancer cells.

PMID- 25379358
TI  - Synthesis, characterization, and stability of iron (III) complex ions possessing
      phenanthroline-based ligands.
AB  - It has previously been demonstrated that phenanthroline-based ligands used to
      make gold metallotherapuetics have the ability to exhibit cytotoxicity when not
      coordinated to the metal center. In an effort to help assess the mechanism by
      which these ligands may cause tumor cell death, iron binding and removal
      experiments have been considered. The close linkage between cell proliferation
      and intracellular iron concentrations suggest that iron deprivation strategies
      may be a mechanism involved in inhibiting tumor cell growth. With the creation of
      iron (III) phen complexes, the iron binding abilities of three polypyridal
      ligands [1,10-phenanthroline (phen), 2,9-dimethyl-1, 10-phenanthroline
      (methylphen), and 2,9-di-sec-butyl-1, 10-phenanthroline ( sec-butylphen)] can be
      tested via a competition reaction with a known iron chelator. Therefore, iron
      (III) complexes possessing all three ligands were synthesized. Initial mass
      spectrometric and infrared absorption data indicate that iron (III) tetrachloride
      complex ions with protonated phen ligands (RphenH+) were formed: [phenH][FeCl4],
      [methylphenH][FeCl4], [ sec-butylphenH][FeCl4]. UV-Vis spectroscopy was used to
      monitor the stability of the complex ions, and it was found that the sec
      butylpheniron complex was more stable than the phen and methylphen analogues.
      This was based on the observation that free ligand was observed immediately upon
      the addition of EDTA to the [phenH][FeCl4] and [methylphenH] [FeCl4] complex
      ions.

PMID- 25379357
TI  - Pharmacologic Means of Extending Lifespan.

PMID- 25379359
TI  - UPDATE ON DEMENTIA WITH LEWY BODIES.
AB  - Dementia with Lewy bodies (DLB) is the second most common form of dementia after
      Alzheimer disease (AD). DLB is characterized pathologically by Lewy body and Lewy
      neuritic pathology, often with variable levels of Alzheimer-type pathology. Core
      clinical features include fluctuating cognition, visual hallucinations, and
      parkinsonism resulting in greater impairments of quality of life, more caregiver
      burden, and higher health-related costs compared with AD. These issues, together
      with a high sensitivity to adverse events with treatment with antipsychotic
      agents, make the need for an early and accurate diagnosis of DLB essential.
      Unfortunately, current consensus criteria are highly specific but lack sufficient
      sensitivity. Use of composite risk scores may improve accuracy of clinical
      diagnosis. Imaging findings, particularly targeting dopaminergic systems have
      shown promise as potential markers to differentiate DLB from AD. A combination of
      non-pharmacologic treatments and pharmacotherapy interventions may maximize
      cognitive function and overall quality of life in DLB patients.

PMID- 25379360
TI  - Novel Flurometric Tool to Assess Mitochondrial Redox State of Isolated Perfused
      Rat Lungs after Exposure to Hyperoxia.
AB  - Recently we demonstrated the utility of optical fluorometry to detect a change in
      the redox status of mitochondrial autofluorescent coenzymes NADH (Nicotinamide
      Adenine Dinucleotide) and FAD (oxidized form of Flavin Adenine Dinucleotide
      (FADH2,)) as a measure of mitochondrial function in isolated perfused rat lungs
      (IPL). The objective of this study was to utilize optical fluorometry to evaluate
      the effect of rat exposure to hyperoxia (>95% O2 for 48 hours) on lung tissue
      mitochondrial redox status of NADH and FAD in a nondestructive manner in IPL.
      Surface NADH and FAD signals were measured before and after lung perfusion with
      perfusate containing rotenone (ROT, complex I inhibitor), potassium cyanide (KCN,
      complex IV inhibitor), and/or pentachlorophenol (PCP, uncoupler). ROT- or KCN
      induced increase in NADH signal is considered a measure of complex I activity,
      and KCN-induced decrease in FAD signal is considered a measure of complex II
      activity. The results show that hyperoxia decreased complex I and II activities
      by 63% and 55%, respectively, as compared to lungs of rats exposed to room air
      (normoxic rats). Mitochondrial complex I and II activities in lung homogenates
      were also lower (77% and 63%, respectively) for hyperoxic than for normoxic
      lungs. These results suggest that the mitochondrial matrix is more reduced in
      hyperoxic lungs than in normoxic lungs, and demonstrate the ability of optical
      fluorometry to detect a change in mitochondrial redox state of hyperoxic lungs
      prior to histological changes characteristic of hyperoxia.

PMID- 25379361
TI  - Comparison of the Growth of Lactobacillus delbrueckii, L. paracasei and L.
      plantarum on Inulin in Co-culture Systems.
AB  - Lactobacillus delbrueckii TU-1, which apparently takes intact inulin into its
      cells and then degrades it intracellularly, was co-cultured in vitro with L.
      paracasei KTN-5, an extracellular inulin degrader; or L. plantarum 22A-3, a
      strain that is able to utilize fructose but not inulin; or both in order to
      prequalify inulin as a prebiotic agent in vivo. When L. delbrueckii TU-1 was co
      cultured with L. paracasei KTN-5 on fructose or inulin, the growth of L.
      delbrueckii TU-1 on inulin was markedly higher than that of L. paracasei KTN-5,
      whereas the growth of L. delbrueckii TU-1 on fructose was much lower than that of
      L. paracasei KTN-5. These results suggest that L. delbrueckii TU-1 and L.
      paracasei KTN-5 were efficient at utilizing inulin and fructose, respectively.
      When L. plantarum 22A-3 was co-cultured with L. delbrueckii TU-1 on inulin, the
      growth of L. plantarum 22A-3 was enhanced by L. paracasei KTN-5 but not by L.
      delbrueckii TU-1, suggesting that the fructose moiety that L. paracasei KTN-5
      released temporarily into the medium was "scavenged" by L. plantarum 22A-3. Thus,
      L. delbrueckii TU-1, L. paracasei KTN-5, and L. plantarum 22A-3 were then
      cultured altogether on inulin. The growth of L. delbrueckii TU-1 was unaffected
      but that of L. paracasei KTN-5 was markedly suppressed. This evidence suggests
      that prebiotic use of inulin supported the selective growth of intracellular
      inulin degraders such as L. delbrueckii rather than extracellular inulin
      degraders such as L. paracasei in the host microbiota. 

PMID- 25379362
TI  - Beneficial Effects of Citrus Juice Fermented with Lactobacillus plantarum YIT
      0132 on Japanese Cedar Pollinosis.
AB  - Recently, the prevalence of allergies in Japan has been increasing. Certain types
      of fruit juice and lactic acid bacteria are known to alleviate allergic symptoms.
      Therefore, we examined whether citrus juice fermented by a specific lactic acid
      bacteria can improve the symptoms of Japanese cedar pollinosis (JCPsis).
      Lactobacillus plantarum YIT 0132 (LP0132) was selected based on its high
      proliferative activity in citrus juice and anti-inflammatory interleukin-10
      inducing activity. Dietary administration of heat-killed LP0132 cells or citrus
      juice fermented with LP0132 was found to significantly suppress nasal rubbing in
      a JCPsis mouse model, indicating relief of allergy symptoms. To evaluate the
      effects of LP0132-fermented citrus juice on pollinosis symptoms and quality of
      life (QOL) in humans with JCPsis, a single-blind, placebo-controlled, parallel
      group clinical trial was conducted. The participants were 42 adults with JCPsis.
      They ingested 100 mL of sterilized LP0132-fermented citrus juice (active group)
      or unfermented citrus juice (placebo group) once daily for 8 weeks. Immediately
      after the pollen peak when allergy symptoms and QOL loss were most severe, itchy
      eyes, itchy skin, and QOL loss by JCPsis were alleviated in the active group
      compared with the placebo group. At 10 weeks after starting the intervention,
      increased the levels of blood eosinophils were significantly suppressed in the
      active group compared with the placebo group. We conclude that continuous
      ingestion of citrus juice fermented with LP0132 may help alleviate the allergy
      symptoms and impaired QOL caused by JCPsis. 

PMID- 25379363
TI  - Lactobacillus acidophilus L-92 Cells Activate Expression of Immunomodulatory
      Genes in THP-1 Cells.
AB  - To understand the immunomodulatory effects of Lactobacillus acidophilus L-92
      cells suggested from our previous study of in vivo anti-allergy and anti-virus
      effects, host immune responses in macrophage-like THP-1 cells after 4 h (the
      early phase) and 24 h (the late phase) of cocultivation with L-92 cells were
      investigated by transcriptome analysis. In the early phase of L-92 treatment,
      various transcription regulator genes, such as, NFkB1, NFkB2, JUN, HIVEP2 and
      RELB, and genes encoding chemokines and cytokines, such as CCL4, CXCL11, CCL3 and
      TNF, were upregulated. Two transmembrane receptor genes, TLR7 and ICAM1, were
      also upregulated in the early phase of treatment. In contrast, many transmembrane
      receptor genes, such as IL7R, CD80, CRLF2, CD86, CD5, HLA-DQA1, IL2RA, IL15RA and
      CSF2RA, and some cytokine genes, including IL6, IL23A and CCL22, were
      significantly upregulated in the late phase after L-92 exposure. Some genes
      encoding cytokines, such as IL1A, IL1B and IL8, and the enzyme IDO1 were
      upregulated at both the early and the late phases of treatment. These results
      suggest that probiotic L-92 might promote Th1 and regulatory T-cell responses by
      activation of the MAPK signaling pathway, followed by the NOD-like receptor
      signaling pathway in THP-1 cells. 

PMID- 25379365
TI  - Causal Inference Under Multiple Versions of Treatment.

PMID- 25379364
TI  - Prevalence of cardio-respiratory factors in the occurrence of the decrease in
      oxygen uptake during supra-maximal, constant-power exercise.
AB  - PURPOSE: To investigate the physiological mechanisms that explain the end
      exercise decrease in oxygen uptake [Formula: see text] during strenuous constant
      power exercise, we recruited eleven trained, track cyclists. METHODS: On two
      separated days they performed 1) resting spirometric measures, followed by an
      incremental test on a cycle ergometer to determine the power output at [Formula:
      see text] and 2) an exhaustive isokinetic supramaximal cycling exercise
      (Tlimsupra) at 185 +/- 24% of [Formula: see text] (i.e., 640.5 +/- 50.8 W).
      During cycling exercise tests, [Formula: see text], ventilation parameters,
      stroke volume (SV) and heart rate were continuously recorded. Furthermore,
      arterialised capillary blood samples were collected to measure blood pH, arterial
      oxygen saturation, lactate and bicarbonate concentration before and 5 min after
      Tlimsupra. RESULTS: A > 5% decrease in [Formula: see text] and/or SV was observed
      in 6 subjects, with 5 out of 6 subjects presenting both phenomena. The magnitude
      of the [Formula: see text] decrease was correlated with the magnitude of the SV
      decrease (R = 0.75, P < 0.01), the peak-exercise end-tidal O2 partial pressure (R
      = 0.80, P < 0.005) and the resting, forced expiratory volume in 1 s (R = 0.72, P
      < 0.05), but not with any blood variables. The significant post-Tlimsupra
      decrease in forced vital capacity and forced inspiratory volume corroborate with
      a possible respiratory muscle fatigue. CONCLUSION: Based on these findings, we
      demonstrate that the occurrence of [Formula: see text] decrease in more than half
      of our subjects, during a strenuous constant-power exercise leading to a mild
      acidosis (pH = 7.21 +/- 0.04), results mainly from cardio-respiratory factors and
      not from blood metabolic responses.

PMID- 25379366
TI  - Summing up again.

PMID- 25379367
TI  - Management of hospital infection control in iran: a need for implementation of
      multidisciplinary approach.
AB  - Nosocomial, or hospital-acquired, infections are considered the most common
      complications affecting hospitalized patients. According to results obtained from
      studies conducted in the Children Medical Center Hospital, a teaching children's
      hospital and a tertiary care referral unit in Tehran, Iran, improvements in
      infection control practices in our hospital seem necessary. The aim of this study
      was to identify risk management and review potential hospital hazards that may
      pose a threat to the health as well as safety and welfare of patients in an
      Iranian referral hospital. Barriers to compliance and poor design of facilities,
      impractical guidelines and policies, lack of a framework for risk management,
      failure to apply behavioral-change theory, and insufficient obligation and
      enforcement by infection control personnel highlight the need of management
      systems in infection control in our hospital. In addition, surveillance and early
      reporting of infections, evaluation of risk-based interventions, and production
      of evidence-based guidelines in our country are recommended. 

PMID- 25379368
TI  - The Recency Period for Estimation of Human Immunodeficiency Virus Incidence by
      the AxSYM Avidity Assay and BED-Capture Enzyme Immunoassay in the Republic of
      Korea.
AB  - OBJECTIVES: Measurement of the incidence of the human immunodeficiency virus
      (HIV) is very important for epidemiological studies. Here, we determined the
      recency period with the AxSYM avidity assay and the BED-capture enzyme
      immunoassay (BED-CEIA) in Korean seroconverters. METHODS: Two hundred
      longitudinal specimens from 81 seroconverters with incident HIV infections that
      had been collected at the Korea National Institute of Health were subjected to
      the AxSYM avidity assay (cutoff = 0.8) and BED-CEIA (cutoff = 0.8). The
      statistical method used to estimate the recency period in recent HIV infections
      was nonparametric survival analyses. Sensitivity and specificity were calculated
      for 10-day increments from 120 days to 230 days to determine the recency period.
      RESULTS: The mean recency period of the avidity assay and BED-CEIA using a
      survival method was 158 days [95% confidence interval (CI), 135-181 days] and 189
      days (95% CI, 170-208 days), respectively. Based on the use of sensitivity and
      specificity, the mean recency period for the avidity assay and BED-CEIA was 150
      days and 200 days, respectively. CONCLUSION: We determined the recency period to
      estimate HIV incidence in Korea. These data showed that the nonparametric
      survival analysis often led to shorter recency periods than analysis of
      sensitivity and specificity as a new method. These findings suggest that more
      data from seroconverters and other methodologies are needed to determine the
      recency period for estimating HIV incidence.

PMID- 25379369
TI  - High Prevalence of Class 1 to 3 Integrons Among Multidrug-Resistant Diarrheagenic
      Escherichia coli in Southwest of Iran.
AB  - OBJECTIVES: Horizontal transfer of integrons is one of the important factors that
      can contribute to the occurrence of multidrug-resistant (MDR) bacteria. This
      study aimed to determine the prevalence of integrons among MDR Escherichia coli
      strains isolated from stool specimens and investigate the associations between
      the existence of integrons and MDR properties in the southwest of Iran. METHODS:
      There were 164 E. coli strains isolated from January 2012 to June 2012. Fecal
      specimens identified as E. coli by the conventional methods. Subsequently the
      antibiotic resistance was assessed using Clinical and Laboratory Standard
      Institute criteria. The presence of class 1-3 integrons and embedded gene
      cassettes was verified using specific primers by multiplex polymerase chain
      reaction assay. RESULTS: Among a total of 164 studied samples, 69 (42.07%)
      isolates were multidrug resistant. Class 1 and class 2 integrons were present in
      78.26% and 76.81% MDR isolates, respectively. For the first time in Iran, class 3
      integron was observed in 26.09% MDR isolates. Significant correlations were
      identified between: class 1 integron and resistance to amikacin, gentamicin,
      chloramphenicol, ampicillin, tetracycline, nalidixic acid, and co-trimoxazole;
      class 2 integron and resistance to aminoglycosides, co-trimoxazole, cefalexin,
      ampicillin, and chloramphenicol; and class 3 integron and resistance to
      gentamicin, kanamycin, and streptomycin. CONCLUSION: Our results indicate that
      integrons are common among MDR isolates and they can be used as a marker for the
      identification of MDR isolates. Therefore, due to the possibility of a widespread
      outbreak of MDR isolates, molecular surveillance and sequencing of the integrons
      in other parts of the country is recommended.

PMID- 25379370
TI  - Knowledge of diabetes mellitus: does gender make a difference?
AB  - OBJECTIVE: Diabetes mellitus (DM) is a chronic disease considered an important
      public health problem. In recent years, its prevalence has been exponentially
      rising in many developing countries. Chronic complications of DM are important
      causes of morbidity and mortality among patients, which impair their health and
      quality of life. Knowledge on disease prevention, etiology, and management is
      essential to deal with parents, patients, and caregivers. The aim of this study
      was to evaluate the knowledge regarding DM in an adult population from a Middle
      western Brazilian city. METHODS: This was a cross-sectional study covering 178
      adults, aged 18-64 years, who answered a diabetes knowledge questionnaire. In
      order to identify the difference between groups, analysis of variance was used.
      RESULTS: Higher knowledge scores were found regarding the role of sugars on DM
      causality, diabetic foot care, and the effects of DM on patients (blindness,
      impaired wound healing, and male sexual dysfunction). However, lower scores were
      found amongst types of DM, hyperglycemic symptoms, and normal blood glucose
      levels. Females tended to achieve better knowledge scores than males. CONCLUSION:
      Women had better knowledge regarding types of DM, normal blood glucose values,
      and consequences of hyperglycemia revealed that diabetes education should be
      improved.

PMID- 25379371
TI  - Relationship between Serum Levels of Body Iron Parameters and Insulin Resistance
      and Metabolic Syndrome in Korean Children.
AB  - OBJECTIVES: An increase in serum ferritin and levels of the cleaved soluble form
      of transferrin receptor (sTfR) are related to several metabolic conditions. We
      evaluated the relationship between body iron status indicators, including
      ferritin and sTfR, and insulin resistance and metabolic syndrome (MetS) in Korean
      children. METHODS: A cross-sectional study was conducted on 1350 children in
      Korea. Anthropometrical parameters; lipid profiles; levels of glucose, insulin,
      and leptin; and iron status indicators, including sTfR, serum ferritin, serum
      iron, total iron-binding capacity (TIBC), and transferrin saturation (TS), were
      analyzed. RESULTS: Although serum sTfR levels were significantly higher in boys
      than in girls (2.20 vs. 2.06 mg/L, p < 0.0001), serum iron and TS were higher in
      girls than in boys (101.38 vs. 95.77 mg/L, p = 0.027 and 30.15 vs. 28.91%, p =
      0.04, respectively). Waist circumference (WC) and leptin were most significantly
      associated with body iron indicators when adjusted for age and sex. After
      adjusting for age, sex, and WC, sTfR levels showed the strongest positive
      association with leptin levels (p = 0.0001). Children in the highest tertile for
      homeostasis model assessment-insulin resistance (HOMA-IR) had higher TIBC (p =
      0.0005) and lower serum iron (p = 0.0341), and the lowest TS (p < 0.0001) after
      adjustment for confounders. Children with higher sTfR were most significantly
      associated with risk of MetS compared with those lower sTfR (p = 0.0077).
      CONCLUSION: The associations of serum levels of iron metabolism markers with
      leptin levels, HOMA-IR, and MetS suggest that iron-related factors may involve
      insulin resistance and MetS.

PMID- 25379372
TI  - A novel approach for predicting disordered regions in a protein sequence.
AB  - OBJECTIVES: A number of published predictors are based on various algorithms and
      disordered protein sequence properties. Although many predictors have been
      published, the study of protein disordered region prediction is ongoing because
      different prediction methods can find different disordered regions in a protein
      sequence. METHODS: Therefore we have used a new approach to find the more varying
      disordered regions for more efficient and accurate prediction of protein
      structures. In this study, we propose a novel approach called "emerging
      subsequence (ES) mining" without using the characteristics of the disordered
      protein. We first adapted the approach to generate emerging protein subsequences
      on public protein sequence data. Second, the disordered and ordered regions in a
      protein sequence were predicted by searching the generated emerging protein
      subsequence with a sliding window, which tends to overlap. Third, the scores of
      the overlapping regions were calculated based on support and growthrate values in
      both classes. Finally, the score of predicted regions in the target class were
      compared with the score of the source class, and the class having a higher score
      was selected. RESULTS: In this experiment, disordered sequence data and ordered
      sequence data was extracted from DisProt 6.02 and PDB respectively and used as
      training data. The test data come from CASP 9 and CASP 10 where disordered and
      ordered regions are known. CONCLUSION: Comparing with several published
      predictors, the results of the experiment show higher accuracy rates than with
      other existing methods.

PMID- 25379373
TI  - Dental Procedures, Oral Practices, and Associated Anxiety: A Study on Late
      teenagers.
AB  - OBJECTIVES: The study aims to determine the degree of anxiety pertaining to
      dental procedures and various oral hygiene practices among college teenagers.
      METHODS: Corah's Modified Dental Anxiety Scale was administered on a randomly
      chosen sample of 100 Indian college students (50 males and 50 females) of Delhi
      University, belonging to the age group of 17-20 years. RESULTS: Descriptive
      statistical computations revealed 12.14 years as the mean age of first dental
      visit, with moderately high levels of anxiety (60.75%) for various dental
      procedures among the Indian teenagers and 5% lying in the "phobic or extremely
      anxious" category. With merely 4.16% people going for regular consultations,
      general check-ups evoked 78.3% anxiety and having an injection or a tooth removed
      was perceived as the most threatening. The sample subgroup not using mouthwash
      and mouthspray, smokers, and alcohol drinkers with improper oral hygiene
      practices experienced much higher anxiety towards routine dental procedures.
      CONCLUSION: The majority of the Indian youngsters had an evasive attitude of
      delaying dental treatment. The core problems lay in deficient health care
      knowledge, lack of patient-sensitive pedagogy to train dental professionals,
      inaccessibility of services, and a dismissive attitude towards medical help. The
      feelings of fear and anxiety prevalent among the Indian youth offer significant
      insights into causes and preventive measures for future research and practice.
      Methods of education and motivation could be developed to dissipate the anxiety
      amongst Indian teenagers that prevent routine dental visits and maintenance of
      adequate oral hygiene.

PMID- 25379374
TI  - A differential equation model for the dynamics of youth gambling.
AB  - OBJECTIVES: We examine the dynamics of gambling among young people aged 16-24
      years, how prevalence rates of at-risk gambling and problem gambling change as
      adolescents enter young adulthood, and prevention and control strategies.
      METHODS: A simple epidemiological model is created using ordinary nonlinear
      differential equations, and a threshold condition that spreads gambling is
      identified through stability analysis. We estimate all the model parameters using
      a longitudinal prevalence study by Winters, Stinchfield, and Botzet to run
      numerical simulations. Parameters to which the system is most sensitive are
      isolated using sensitivity analysis. RESULTS: Problem gambling is endemic among
      young people, with a steady prevalence of approximately 4-5%. The prevalence of
      problem gambling is lower in young adults aged 18-24 years than in adolescents
      aged 16-18 years. At-risk gambling among young adults has increased. The
      parameters to which the system is most sensitive correspond to primary
      prevention. CONCLUSION: Prevention and control strategies for gambling should
      involve school education. A mathematical model that includes the effect of early
      exposure to gambling would be helpful if a longitudinal study can provide data in
      the future.

PMID- 25379375
TI  - Fungal colonization with Pneumocystis correlates to increasing chloride channel
      accessory 1 (hCLCA1) suggesting a pathway for up-regulation of airway mucus
      responses, in infant lungs.
AB  - Fungal colonization with Pneumocystis is associated with increased airway mucus
      in infants during their primary Pneumocystis infection, and to severity of COPD
      in adults. The pathogenic mechanisms are under investigation. Interestingly,
      increased levels of hCLCA1 - a member of the calcium-sensitive chloride
      conductance family of proteins that drives mucus hypersecretion - have been
      associated with increased mucus production in patients diagnosed with COPD and in
      immunocompetent rodents with Pneumocystis infection. Pneumocystis is highly
      prevalent in infants; therefore, the contribution of Pneumocystis to hCLCA1
      expression was examined in autopsied infant lungs. Respiratory viruses that may
      potentially increase mucus, were also examined. hCLCA1 expression was measured
      using actin-normalized Western-blot, and the burden of Pneumocystis organisms was
      quantified by qPCR in 55 autopsied lungs from apparently healthy infants who died
      in the community. Respiratory viruses were diagnosed using RT-PCR for RSV,
      metapneumovirus, influenza, and parainfluenza viruses; and by PCR for adenovirus.
      hCLCA1 levels in virus positive samples were comparable to those in virus
      negative samples. An association between Pneumocystis and increased hCLCA1
      expression was documented (P=0.028). Additionally, increasing Pneumocystis burden
      correlated with increasing hCLCA1 protein expression levels (P=0.017). Results
      strengthen the evidence of Pneumocystis-associated up-regulation of mucus-related
      airway responses in infant lungs. Further characterization of this
      immunocompetent host-Pneumocystis-interaction, including assessment of potential
      clinical significance, is warranted. 

PMID- 25379376
TI  - Extracellular ATP does not induce P2X7 receptor-dependent responses in cultured
      renal- and liver-derived swine macrophages.
AB  - The P2X7 receptor (P2X7R) is an ATP-gated cation channel that is abundantly
      expressed in monocytes/macrophages. P2X7R activation by ATP results in various
      cellular responses including Ca(2+) influx, membrane pore formation, and cytokine
      secretion. Since P2X7R has low affinity for ATP, high concentrations of ATP (in
      the mM range) are generally required to activate this receptor in vitro.
      Functional expression of P2X7R has been detected in monocytes/macrophages
      obtained from different animal species including humans, rodents, dogs, and
      bovines, but so far it has not been detected in swine (Sus scrofa). In this
      study, we investigated the expression and functions of P2X7R in swine
      macrophages, which were isolated from mixed primary cultures of swine kidney or
      liver tissue. The P2X7R mRNA and protein expression observed in the swine
      macrophages was comparable to that seen in a c-myc-immortalized mouse kidney
      derived clonal macrophage cell line (KM-1). However, extracellular ATP did not
      induce P2X7R-dependent sustained Ca(2+) influx, membrane pore formation, or the
      secretion of the bioactive cytokine interleukin-1beta in the swine macrophages,
      whereas these responses were clearly observed in the mouse KM-1 cells after
      stimulation with millimolar concentrations of ATP as a positive control. These
      findings suggest that the ATP/P2X7R pathway is impaired in swine macrophages at
      least in the culture conditions used in the present study. 

PMID- 25379377
TI  - Establishment of c-myc-immortalized Kupffer cell line from a C57BL/6 mouse
      strain.
AB  - We recently demonstrated in several mammalian species, a novel procedure to
      obtain liver-macrophages (Kupffer cells) in sufficient numbers and purity using a
      mixed primary culture of hepatocytes. In this study, we applied this method to
      the C57BL/6 mouse liver and established an immortalized Kupffer cell line from
      this mouse strain. The hepatocytes from the C57BL/6 adult mouse liver were
      isolated by a two-step collagenase perfusion method and cultured in T25 culture
      flasks. Similar to our previous studies, the mouse hepatocytes progressively
      changed their morphology into a fibroblastic appearance after a few days of
      culture. After 7-10 days of culture, Kupffer-like cells, which were contaminants
      in the hepatocyte fraction at the start of the culture, actively proliferated on
      the mixed fibroblastic cell sheet. At this stage, a retroviral vector containing
      the human c-myc oncogene and neomycin resistance gene was introduced into the
      mixed culture. Gentle shaking of the culture flask, followed by the transfer and
      brief incubation of the culture supernatant, resulted in a quick and selective
      adhesion of Kupffer cells to a plastic dish surface. After selection with G418
      and cloning by limiting dilutions, a clonal cell line (KUP5) was established.
      KUP5 cells displayed typical macrophage morphology and were stably passaged at 4
      5 days intervals for more than 5 months, with a population doubling time of 19 h.
      KUP5 cells are immunocytochemically positive for mouse macrophage markers, such
      as Mac-1, F4/80. KUP5 cells exhibited substantial phagocytosis of polystyrene
      microbeads and the release of inflammatory cytokines upon lipopolysaccharide
      stimulation. Taken together, KUP5 cells provide a useful means to study the
      function of Kupffer cells in vitro. 

PMID- 25379378
TI  - Mycobacterium tuberculosis PE25/PPE41 protein complex induces necrosis in
      macrophages: Role in virulence and disease reactivation?
AB  - Necrotic cell death during TB infection is an important prerequisite for
      bacterial dissemination and virulence. The underlying mechanisms and the
      bacterial factors involved therein are not well understood. The Mycobacterium
      tuberculosis (M. tuberculosis) co-operonic PE25/PPE41 protein complex, similar to
      ESAT-6/CFP-10, belonging to the PE/PPE and ESAT-6 families of genes has co
      expanded and co-evolved in the genomes of pathogenic mycobacteria. We report a
      novel role of this highly immunogenic PE25/PPE41 protein complex in inducing
      necrosis, but not apoptosis, in macrophages. We propose that these protein
      complexes of M. tuberculosis, secreted by similar/unique transport system (Type
      VII), have an important role in M. tuberculosis virulence and disease
      reactivation. 

PMID- 25379379
TI  - A new pma1 mutation identified in a chronologically long-lived fission yeast
      mutant.
AB  - We isolated a chronologically long-lived mutant of Schizosaccharomyces pombe and
      found a new mutation in pma1 (+) that encoded for an essential P-type proton
      ATPase. An Asp-138 to Asn mutation resulted in reduced Pma1 activity, concomitant
      with an increase in the chronological lifespan of this fission yeast. This study
      corroborates our previous report indicating Pma1 activity is crucial for the
      determination of life span of fission yeast, and offers information for better
      understanding of the enzyme, Pma1. 

PMID- 25379380
TI  - An alternative allosteric regulation mechanism of an acidophilic l-lactate
      dehydrogenase from Enterococcus mundtii 15-1A.
AB  - A plant-derived Enterococcus mundtii 15-1A, that has been previously isolated
      from Brassica rapa L. subsp. nipposinica (L.H. Bailey) Hanelt var. linearifolia
      by our group, possesses two kinds of l-lactate dehydrogenase (l-LDH): LDH-1 and
      LDH-2. LDH-1 was activated under low concentration of fluctose-1,6-bisphosphate
      (FBP) at both pH 5.5 and 7.5. Although LDH-2 was also activated under the low
      concentration of FBP at pH 5.5, a high concentration of FBP is necessary to
      activate it at pH 7.5. The present study shows the crystal structures of the
      acidophilic LDH-2 in a complex with and without FBP and NADH. Although the
      tertiary structure of the ligands-bound LDH-2 is similar to that of the active
      form of other bacterial l-LDHs, the structure without the ligands is different
      from that of any other previously determined l-LDHs. Major structural alterations
      between the two structures of LDH-2 were observed at two regions in one subunit.
      At the N-terminal parts of the two regions, the ligands-bound form takes an alpha
      helical structure, while the form without ligands displays more disordered and
      extended structures. A vacuum-ultraviolet circular dichroism analysis showed that
      the alpha-helix content of LDH-2 in solution is approximately 30% at pH 7.5,
      which is close to that in the crystal structure of the form without ligands. A
      D241N mutant of LDH-2, which was created by us to easily form an alpha-helix at
      one of the two parts, exhibited catalytic activity even in the absence of FBP at
      both pH 5.5 and 7.5. 

PMID- 25379381
TI  - Irreversible hyperoxidation of peroxiredoxin 2 is caused by tert-butyl
      hydroperoxide in human red blood cells.
AB  - Peroxiredoxin 2 (Prx2) is the third most abundant protein in red blood cells
      (RBCs). In this study, we have succeeded in implementing the rapid and
      simultaneous detection of the hyperoxidized (Prx2-SO2/3) and reduced (Prx2-SH)
      forms of Prx2 in human RBCs using reverse phase high-performance liquid
      chromatography. The detection of a peak corresponding to Prx2-SO2/3 was clearly
      observed following treatment of tert-butyl hydroperoxide (t-BHP), but not H2O2,
      and was found to be dose-dependent. The identity of the peak was confirmed as
      Prx2 by immunoblotting and mass spectrometry analysis. Our results suggest that t
      BHP hyperoxidizes cysteine residues in Prx2 more readily than H2O2, and that
      accumulation of hyperoxidized Prx2 might reflect disruption of redox homeostasis
      in RBCs. 

PMID- 25379382
TI  - Contribution of protein phosphorylation to binding-induced folding of the SLBP
      histone mRNA complex probed by phosphorus-31 NMR.
AB  - Phosphorus-31 ((31)P) NMR can be used to characterize the structure and dynamics
      of phosphorylated proteins. Here, I use (31)P NMR to report on the chemical
      nature of a phosphothreonine that lies in the RNA binding domain of SLBP (stem
      loop binding protein). SLBP is an intrinsically disordered protein and
      phosphorylation at this threonine promotes the assembly of the SLBP-RNA complex.
      The data show that the (31)P chemical shift can be a good spectroscopic probe for
      phosphate-coupled folding and binding processes in intrinsically disordered
      proteins, particularly where the phosphate exhibits torsional strain and is
      involved in a network of hydrogen-bonding interactions. 

PMID- 25379383
TI  - Structural and functional characterization of salmon STAT1, STAT2 and IRF9
      homologs sheds light on interferon signaling in teleosts.
AB  - Mammalian IRF9 and STAT2, together with STAT1, form the ISGF3 transcription
      factor complex, which is critical for type I interferon (IFN)-induced signaling,
      while IFNgamma stimulation is mediated by homodimeric STAT1 protein. Teleost fish
      are known to possess most JAK and STAT family members, however, description of
      their functional activity in lower vertebrates is still scarce. In the present
      study we have identified two different STAT2 homologs and one IRF9 homolog from
      Atlantic salmon (Salmo salar). Both proteins have domain-like structures with
      functional motifs that are similar to higher vertebrates, suggesting that they
      are orthologs to mammalian STAT2 and IRF9. The two identified salmon STAT2s,
      named STAT2a and STAT2b, showed high sequence identity but were divergent in
      their transactivation domain (TAD). Like STAT1, ectopically expressed STAT2a and
      b were shown to be tyrosine phosphorylated by type I IFNs and, interestingly,
      also by IFNgamma. Microscopy analyses demonstrated that STAT2 co-localized with
      STAT1a in the cytoplasm of unstimulated cells, while IFNa1 and IFNgamma
      stimulation seemed to favor their nuclear localization. Overexpression of STAT2a
      or STAT2b together with STAT1a activated a GAS-containing reporter gene construct
      in IFNgamma-stimulated cells. The highest induction of GAS promoter activation
      was found in IFNgamma-stimulated cells transfected with IRF9 alone. Taken
      together, these data suggest that salmon STAT2 and IRF9 may have a role in
      IFNgamma-induced signaling and promote the expression of GAS-driven genes in bony
      fish. Since mammalian STAT2 is primarily an ISGF3 component and not involved in
      IFNgamma signaling, our finding features a novel role for STAT2 in fish. 

PMID- 25379384
TI  - Porcine SLITRK1: Molecular cloning and characterization.
AB  - The membrane protein SLITRK1 functions as a developmentally regulated stimulator
      of neurite outgrowth and variants in this gene have been implicated in Tourette
      syndrome. In the current study we have cloned and characterized the porcine
      SLITRK1 gene. The genomic organization of SLITRK1 lacks introns, as does its
      human and mouse counterparts. RT-PCR cloning revealed two SLITRK1 transcripts: a
      full-length mRNA and a transcript variant that results in a truncated protein.
      The encoded SLITRK1 protein, consisting of 695 amino acids, displays a very high
      homology to human SLITRK1 (99%). The porcine SLITRK1 gene is expressed
      exclusively in brain tissues. 

PMID- 25379385
TI  - N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion,
      which is unrelated to lipoid proteinosis.
AB  - Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues
      and plays important roles in extracellular matrix formation. Additionally, ECM1
      gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic
      origin. However, an effective therapeutic approach of LP is not established.
      Here, we showed that ECM1 gene mutation observed in LP patients significantly
      suppresses its secretion. As ECM1 has three putative N-glycosylation sites and
      most of mutated ECM1 observed in LP patients are defective in these N
      glycosylation sites, we investigated the correlation between LP and N
      glycosylation of ECM1. We identified that the Asn(354) and Asn(444) residues in
      ECM1 were N-glycosylated by mass spectrometry analysis. In addition, an N-linked
      glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient
      derived mutants. These results indicate that the defect of N-glycosylation in
      ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1. 

PMID- 25379386
TI  - Prenatal expression of thioredoxin reductase 1 (TRXR1) and microsomal glutathione
      transferase 1 (MGST1) in humans.
AB  - Thioredoxin reductase 1 (TRXR1) and microsomal glutathione transferase 1 (MGST1)
      are important redox and detoxifying enzymes in adult life. The aim of this study
      was to investigate the expression of these enzymes during fetal life. In
      addition, the role of gene methylation was studied since this might play an
      important role in the on-and-off switch of gene expression between fetal and
      adult life. To this end, the expression of the TRXR1-encoding gene TXNRD1 and the
      MGST1-encoding gene MGST1 was studied in fetal tissues. The mean mRNA expression
      of TXNRD1 in fetal livers were seven times higher compared to the mean expression
      in adult livers (p < 0.001). Of the six studied splice variants of TXNRD1, four
      had a significantly higher expression in the fetal livers as compared to adult
      livers. The mean expression of MGST1 was twofold higher in adult compared to
      fetal liver tissue (p = 0.01). For MGST1 the alternative first exon 1B was the
      predominant splice variant in both fetal and adult liver samples. The highest
      mRNA expression of both TXNRD1 and MGST1 was found in fetal adrenals, whereas
      expression was lower in fetal liver, lungs and kidneys. There was a significant
      correlation between the hepatic expression of TXNRD1 and MGST1. Treatment with
      the demethylating agent 5-AZA resulted in decreased levels of TXNRD1 in human
      liver HepG2 cells but did not affect the expression of MGST1. In conclusion, the
      expression of TXNRD1 is higher in fetuses than in adults and might be of
      importance during fetal life. Hepatic TXNRD1 and MGST1 are co-expressed in both
      fetuses and adults suggesting common regulatory mechanisms. 

PMID- 25379388
TI  - Acute respiratory distress caused by Neosartorya udagawae.
AB  - We describe the first reported case of acute respiratory distress syndrome (ARDS)
      attributed to Neosartorya udagawae infection. This mold grew rapidly in cultures
      of multiple respiratory specimens from a previously healthy 43-year-old woman.
      Neosartorya spp. are a recently recognized cause of invasive disease in
      immunocompromised patients that can be mistaken for their sexual teleomorph,
      Aspergillus fumigatus. Because the cultures were sterile, phenotypic
      identification was not possible. DNA sequencing of ITS, calmodulin and beta
      tubulin genes supported identification of Neosartorya udagawae. Our case is the
      first report of ARDS associated with Neosartorya sp. infection and defines a new
      clinical entity. 

PMID- 25379387
TI  - Cell surface N-glycans influence the level of functional E-cadherin at the cell
      cell border.
AB  - E-cadherin is crucial for adhesion of cells to each other and thereby development
      and maintenance of tissue. While it is has been established that N-glycans inside
      the cell impact the level of E-cadherin at the cell surface of epithelial-derived
      cells, it is unclear whether N-glycans outside the cell control the clustering of
      E-cadherin at the cell-cell border. Here, we demonstrate reduction of N-glycans
      at the cell surface weakened the recruitment and retention of E-cadherin at the
      cell-cell border, and consequently reduced the strength of cell-cell
      interactions. We conclude that N-glycans at the cell surface are tightly linked
      to the placement of E-cadherin at the cell-cell border and thereby control E
      cadherin mediated cell-cell adhesion. 

PMID- 25379389
TI  - Vertebral infection with Candida albicans failing caspofungin and fluconazole
      combination therapy but successfully treated with high dose liposomal
      amphotericin B and flucytosine.
AB  - A patient with Candida spondylitis failed two weeks of fluconazole combined with
      caspofungin, and the infection relapsed despite six weeks of liposomal
      amphotericin B followed by two months of fluconazole. Six months therapy with
      high dose liposomal amphotericin B combined with flucytosine effectively cured
      the patient. 

PMID- 25379390
TI  - Central nervous system cryptococcoma in a Ugandan patient with Human
      Immunodeficiency Virus.
AB  - Mortality due to AIDS-related Cryptococcal meningitis (CM) is often >50% in low
      middle income countries. Dissemination of CM can result in intracranial mass
      lesions known as cryptococcoma. Patients who develop cryptococcomas often have
      worse outcomes when compared to patients with cryptococcosis without
      cryptococcoma. We describe a cryptococcoma in the central nervous system (CNS) in
      a Ugandan patient with AIDS, and review the diagnosis and management with special
      focus on difficulties encountered in low or middle-income countries. 

PMID- 25379391
TI  - Multifocal Rhizopus microsporus lung infection following brush clearing.
AB  - We report a case of pulmonary Rhizopus microsporus infection in a patient with
      untreated diabetes following brush clearing. The patient was successfully treated
      with a combined medical and surgical approach with complete resolution of the
      lung lesions and remains asymptomatic at 11-month follow-up. 

PMID- 25379392
TI  - Disseminated mucormycosis in a paediatric patient: Lichthemia corymbifera
      successfully treated with combination antifungal therapy.
AB  - Mucormycosis is a severe fungal infection that largely affects immunocompromised
      individuals. It carries a high morbidity and mortality rate and is characterised
      by extensive angioinvasion and necrosis of host tissue. This case report details
      success in treating disseminated mucormycosis in a paediatric patient with an
      underlying haematological malignancy. Treatment included institution of
      combination antifungal therapy with liposomal amphotericin B and caspofungin,
      aggressive surgical debridement of infected tissue and reversal of underlying
      immunosuppression. 

PMID- 25379393
TI  - Miliary pulmonary cryptococcosis.
AB  - A 32-year-old HIV positive male presents with fevers and a non-productive cough.
      Initial X-ray and subsequent computerised tomography of the chest shows a
      bilateral miliary pattern of pulmonary infiltration highly suggestive of
      disseminated tuberculosis. However subsequent results were consistent with
      disseminated cryptococcosis, including pulmonary involvement, with cryptococcus
      identified on transbronchial tissue biopsy, and on blood and cerebrospinal fluid
      cultures. Imaging features of pulmonary cryptococcosis are generally of well
      defined pleural-based nodules and less commonly alveolar infiltrates,
      lymphadenopathy, pleural effusions or cavitating lesions. Miliary pulmonary
      infiltrates are an exceptionally rare presentation. 

PMID- 25379394
TI  - Aspergillus tracheobronchitis, bronchopleural fistula and empyema after lobectomy
      for aspergilloma.
AB  - Aspergillus tracheobronchitis and Aspergillus empyema are two rare manifestations
      of Aspergillus infection. This case report presents a patient with chronic
      obstructive pulmonary disease who developed a pseudomembranous Aspergillus
      tracheobronchitis, bronchopleural fistula and empyema 16 months after lobectomy
      for an aspergilloma. Bronchoscopy proved to be important for assessment of
      severity. Combined systemic anti-fungal treatment (voriconazole) and open window
      thoracostomy were used to successfully treat the patient. 

PMID- 25379395
TI  - Blastomycosis in a postpartum dog.
AB  - Transplacental infection with Blastomyces dermatitidis is rare in humans and
      unknown in the dog. A Doberman pinscher bitch was diagnosed with blastomycosis 25
      days after whelping. Clinical signs were noted after whelping and were
      progressive. All 9 pups were free of clinical signs and had negative urine
      Blastomyces antigen tests at 6 weeks of age and remained free of signs of illness
      through 11 months of age. The bitch responded to treatment with itraconazole. 

PMID- 25379396
TI  - Primary cutaneous cryptococcosis caused by Cryptococcus gattii VGII in a tsunami
      survivor from Thailand.
AB  - Skin and soft tissue fungal infections with Apophysomyces elegans, Fusarium
      solani, Cladophialophora bantiana have been reported in survivors from 2004
      Indian ocean Tsunami. We report the first case of primary cutaneous
      cryptococcosis caused by Cryptococcus gattii VGII in a Tsunami survivor from
      Thailand. 

PMID- 25379397
TI  - Pneumocystis jirovecii pneumonia following everolimus treatment of metastatic
      breast cancer.
AB  - Everolimus is an inhibitor of mammalian target of rapamycin with anti-tumour
      activity. While everolimus is known to cause drug-induced pneumonitis, it is
      rarely associated with Pneumocystis jirovecii pneumonia (PJP). We report a
      patient on everolimus therapy for metastatic breast cancer that developed PJP.
      Diagnosis was based on clinical features and a quantitative polymerase chain
      reaction for P. jirovecii DNA. Clinicians should consider PJP as a potential
      cause of pulmonary infiltrates in patients treated with everolimus. 

PMID- 25379398
TI  - Candida albicans endophthalmitis in a patient with a non-functioning pituitary
      adenoma evolving into Cushing's disease: A case report.
AB  - A 53-year-old woman presented with complaints of blurred vision in the left eye.
      She had been treated for recurrent non-functioning pituitary adenoma (NFPA). A
      vitreous biopsy followed by histopathologic examination showed the presence of
      Candida albicans. Meanwhile, Cushing's disease was diagnosed and gamma knife
      surgery was performed. Vitrectomy and antifungal treatment improved ocular
      infection and inflammation. Herein, we describe the first case of C. albicans
      endophthalmitis in a patient with NFPA evolving into Cushing's disease. 

PMID- 25379399
TI  - Occurrence of fruiting structures allows determination of Purpureocillium
      lilacinum as an inciting agent of pleuritis and pneumonia in a loggerhead sea
      turtle (Caretta caretta) by histopathologic correlation to culture.
AB  - Purpureocillium lilacinum and Beauveria bassiana were isolated from lung sampled
      at necropsy of a 12 year-old female loggerhead sea turtle (Caretta caretta) that
      had displayed abnormal buoyancy. Histopathologic evaluation revealed pleuritis
      and pneumonia with non-melanized, septate hyphae and fruiting structures
      identical to those of P. lilacinum. This case emphasizes the importance of a
      histological correlate to fungal culture when environmental fungi are isolated
      and demonstrates the infrequent phenomenon of fruiting or conidial production in
      tissue. 

PMID- 25379400
TI  - Rhodotorula mucilaginosa associacted meningitis: A subacute entity with high
      mortality. Case report and review.
AB  - A fatal case of meningitis due to Rhodotorula mucilaginosa in a 28 year-old HIV
      negative male with a history of Hodgkin lymphoma who underwent salvage
      chemotherapy is presented. Reviewing the literature we identified 13 cases with
      central nervous system infection due Rhodotorula spp. The disease usually occurs
      in HIV negative immunosupressed middle-aged males. It takes the form of subacute
      or chronic meningitis accompanied by fever with an overall mortality of 46.2%
      despite antifungal therapy. 

PMID- 25379401
TI  - Mucor irregularis-associated cutaneous mucormycosis: Case report and review.
AB  - Solid organ transplant recipients are at risk for invasive fungal diseases, and
      are also exposed to healthcare-associated mucormycosis. Mainly causing localized
      cutaneous mucormycosis, Mucor irregularis infection is reported for the first
      time in a kidney-transplant recipient. A healthcare-associated origin was highly
      suspected in this case. We performed a literature review and highlight the
      characteristics of this very rare fungus. 

PMID- 25379402
TI  - Why leptin keeps you warm.

PMID- 25379403
TI  - Chaperoning to the metabolic party: The emerging therapeutic role of heat-shock
      proteins in obesity and type 2 diabetes.
AB  - BACKGROUND: From their initial, accidental discovery 50 years ago, the highly
      conserved Heat Shock Proteins (HSPs) continue to exhibit fundamental roles in the
      protection of cell integrity. Meanwhile, in the midst of an obesity epidemic,
      research demonstrates a key involvement of low grade inflammation, and
      mitochondrial dysfunction amongst other mechanisms, in the pathology of insulin
      resistance and type 2 diabetes mellitus (T2DM). In particular, tumor necrosis
      factor alpha (TNFalpha), endoplasmic reticulum (ER) and oxidative stress all
      appear to be associated with obesity and stimulate inflammatory kinases such as c
      jun amino terminal kinase (JNK), inhibitor of NF-kappabeta kinase (IKK) and
      protein kinase C (PKC) which in turn, inhibit insulin signaling. Mitochondrial
      dysfunction in skeletal muscle has also been proposed to be prominent in the
      pathogenesis of T2DM either by reducing the ability to oxidize fatty acids,
      leading to the accumulation of deleterious lipid species in peripheral tissues
      such as skeletal muscle and liver, or by altering the cellular redox state. Since
      HSPs act as molecular chaperones and demonstrate crucial protective functions in
      stressed cells, we and others have postulated that the manipulation of HSP
      expression in metabolically relevant tissues represents a therapeutic avenue for
      obesity-induced insulin resistance. SCOPE OF REVIEW: This review summarizes the
      literature from both animal and human studies, that has examined how HSPs,
      particularly the inducible HSP, Heat Shock Protein 72 (Hsp72) alters glucose
      homeostasis and the possible approaches to modulating Hsp72 expression. A
      summation of the role of chemical chaperones in metabolic disorders is also
      included. MAJOR CONCLUSIONS: Targeted manipulation of Hsp72 or use of chemical
      chaperiones may have clinical utility in treating metabolic disorders such as
      insulin resistance and T2DM.

PMID- 25379404
TI  - The Polycomb protein, Bmi1, regulates insulin sensitivity.
AB  - OBJECTIVE: The Polycomb Repressive Complexes (PRC) 1 and 2 function to
      epigenetically repress target genes. The PRC1 component, Bmi1, plays a crucial
      role in maintenance of glucose homeostasis and beta cell mass through repression
      of the Ink4a/Arf locus. Here we have explored the role of Bmi1 in regulating
      glucose homeostasis in the adult animal, which had not been previously reported
      due to poor postnatal survival of Bmi1 (-/-) mice. METHODS: The metabolic
      phenotype of Bmi1 (+/-) mice was characterized, both in vivo and ex vivo. Glucose
      and insulin tolerance tests and hyperinsulinemic-euglycemic clamps were
      performed. The insulin signaling pathway was assessed at the protein and
      transcript level. RESULTS: Here we report a negative correlation between Bmi1
      levels and insulin sensitivity in two models of insulin resistance, aging and
      liver-specific insulin receptor deficiency. Further, heterozygous loss of Bmi1
      results in increased insulin sensitivity in adult mice, with no impact on body
      weight or composition. Hyperinsulinemic-euglycemic clamp reveals increased
      suppression of hepatic glucose production and increased glucose disposal rate,
      indicating elevated glucose uptake to peripheral tissues, in Bmi1 (+/-) mice.
      Enhancement of insulin signaling, specifically an increase in Akt
      phosphorylation, in liver and, to a lesser extent, in muscle appears to
      contribute to this phenotype. CONCLUSIONS: Together, these data define a new role
      for Bmi1 in regulating insulin sensitivity via enhancement of Akt
      phosphorylation.

PMID- 25379406
TI  - Combination therapy with interferon and JAK1-2 inhibitor is feasible: Proof of
      concept with rapid reduction in JAK2V617F-allele burden in polycythemia vera.
AB  - We report a 55 year old woman with post-ET PV for 12 years, who experienced
      resolution of severe constitutional symptoms within 3 days, a marked reduction in
      splenomegaly and a rapid decline in the JAK2V617F allele burden during
      combination therapy with interferon-alpha2a and ruxolitinib. Within 4 weeks the
      patient achieved complete hematological remission with normalization of
      peripheral blood counts and within 10 months the JAK2V617F-allele burden was
      reduced from 90% to 28%. Such a rapid decline in the JAK2V617F allele burden is
      highly unusual in PV-patients during low-dose IFN-alpha2 monotherapy and this
      finding warrants a prospective study with combination therapy. 

PMID- 25379405
TI  - CREB mediates the insulinotropic and anti-apoptotic effects of GLP-1 signaling in
      adult mouse beta-cells.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) plays a major role in pancreatic beta
      cell function and survival by increasing cytoplasmic cAMP levels, which are
      thought to affect transcription through activation of the basic leucine zipper
      (bZIP) transcription factor CREB. Here, we test CREB function in the adult beta
      cell through inducible gene deletion. METHODS: We employed cell type-specific and
      inducible gene ablation to determine CREB function in pancreatic beta-cells in
      mice. RESULTS: By ablating CREB acutely in mature beta-cells in tamoxifen-treated
      Creb (loxP/loxP);Pdx1-CreERT2 mice, we show that CREB has little impact on beta
      cell turnover, in contrast to what had been postulated previously. Rather, CREB
      is required for GLP-1 to elicit its full effects on stimulating glucose-induced
      insulin secretion and protection from cytokine-induced apoptosis.
      Mechanistically, we find that CREB regulates expression of the pro-apoptotic gene
      p21 (Cdkn1a) in beta-cells, thus demonstrating that CREB is essential to
      mediating this critical aspect of GLP-1 receptor signaling. CONCLUSIONS: In sum,
      our studies using conditional gene deletion put into question current notions
      about the importance of CREB in regulating beta-cell function and mass. However,
      we reveal an important role for CREB in the beta-cell response to GLP-1 receptor
      signaling, further validating CREB as a therapeutic target for diabetes.

PMID- 25379407
TI  - Interaction between IL-6 and TNF-alpha genotypes associated with bacteremia in
      multiple myeloma patients submitted to autologous stem cell transplantation
      (ASCT).
AB  - Stem cell transplantation affects patient's vulnerability to infections due to
      immunological changes related to chemotherapy. Multiple myeloma is characterized
      by susceptibility to infections, and IL-6 and TNF-alpha increased levels affect
      immune response (IR). Polymorphisms in promoter region of cytokine genes may
      alter expression levels and affect IR. We performed interaction analysis of IL-6
      (-174G/C) and TNF-alpha (-308G/A) polymorphisms with infection susceptibility in
      148 patients classified accordingly to infection status and found an interaction
      when compared groups with and without bacteremia (p=0.0380). The interaction may
      be more important than single effects for the IR associated with the infection
      susceptibility in ASCT. 

PMID- 25379408
TI  - The BH3-mimetic ABT-737 effectively kills acute myeloid leukemia initiating
      cells.
AB  - The anti-apoptotic proteins Bcl-XL and Bcl-2 are abundantly expressed in
      hematopoietic stem cells and/or progenitor cells. Furthermore, leukemic cells
      expressing these proteins are enriched in minimal residual disease cell
      populations. This prompted us to test the BH3-mimetic compound ABT-737 for its
      ability to eradicate putative leukemic stem cells. ABT-737 demonstrated potent
      cytotoxic effects in all patient samples tested. The efficacy of ABT-737 against
      AML blasts and the primitive CD34(+)/CD38(-) population was equal and independent
      of sensitivity to cytarabine/daunorubicin. These results, together with
      previously reported synergistic effects of ABT-737 with chemotherapeutics make
      BH3-mimetics promising candidates for future AML treatment regimens. 

PMID- 25379409
TI  - An unusual case of splenomegaly and increased lactate dehydrogenase heralding
      acute myeloid leukemia with eosinophilia and RUNX1-MECOM fusion transcripts.
AB  - We report the first case of acute myeloid leukemia (AML) with RUNX1-MECOM fusion
      transcripts, showing marked eosinophilia. A 63-year old man admitted in August
      2013, had previously been observed in April 2013, because of persisting
      homogeneous splenomegaly and increased LDH, which were initially attributed to
      both minor beta-thalassemia and previous acute myocardial infarction. However,
      based upon the retrospective analysis of clinical features combined with the
      documentation of both JAK2 V617F and c-KIT D816V mutations at AML diagnosis, an
      aggressive leukemic transformation with eosinophilia of a previously unrecognized
      myeloproliferative neoplasm, rather than the occurrence of de novo AML, may be
      hypothesized. 

PMID- 25379410
TI  - Deletion and deletion/insertion mutations in the juxtamembrane domain of the FLT3
      gene in adult acute myeloid leukemia.
AB  - In contrast to FLT3 ITD mutations, in-frame deletions in the FLT3 gene have
      rarely been described in adult acute leukemia. We report two cases of AML with
      uncommon in-frame mutations in the juxtamembrane domain of the FLT3 gene: a 3-bp
      (c.1770_1774delCTACGinsGT; p.F590_V592delinsLF) deletion/insertion and a 12-bp
      (c.1780_1791delTTCAGAGAATAT; p.F594_Y597del) deletion. We verified by sequencing
      that the reading frame of the FLT3 gene was preserved and by cDNA analysis that
      the mRNA of the mutant allele was expressed in both cases. Given the recent
      development of FLT3 inhibitors, our findings may be of therapeutic value for AML
      patients harboring similar FLT3 mutations. 

PMID- 25379411
TI  - Arterial spin labelling reveals prolonged arterial arrival time in idiopathic
      Parkinson's disease.
AB  - Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative
      disease, yet effective disease modifying treatments are still lacking.
      Neurodegeneration involves multiple interacting pathological pathways. The extent
      to which neurovascular mechanisms are involved is not well defined in IPD. We
      aimed to determine whether novel magnetic resonance imaging (MRI) techniques,
      including arterial spin labelling (ASL) quantification of cerebral perfusion, can
      reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD
      (mean +/- SD age 65.1 +/- 5.9 years) and 14 age and cardiovascular risk factor
      matched control participants (mean +/- SD age 64.6 +/- 4.2 years) underwent a 3T
      MRI scan protocol. ASL images were collected before, during and after a 6 minute
      hypercapnic challenge. FLAIR images were used to determine white matter lesion
      score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time
      (AAT) were calculated from the ASL data both at rest and during hypercapnia.
      Cerebrovascular reactivity (CVR) images were calculated, depicting the change in
      CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005)
      increase in whole brain averaged baseline AAT was observed in IPD participants
      (mean +/- SD age 1532 +/- 138 ms) compared to controls (mean +/- SD age 1335 +/-
      165 ms). Voxel-wise analysis revealed this to be widespread across the brain.
      However, there were no statistically significant differences in white matter
      lesion score, CBF, or CVR between patients and controls. Regional CBF, but not
      AAT, in the IPD group was found to correlate positively with Montreal cognitive
      assessment (MoCA) scores. These findings provide further evidence of alterations
      in NVS in IPD.

PMID- 25379412
TI  - Statistical normalization techniques for magnetic resonance imaging.
AB  - While computed tomography and other imaging techniques are measured in absolute
      units with physical meaning, magnetic resonance images are expressed in arbitrary
      units that are difficult to interpret and differ between study visits and
      subjects. Much work in the image processing literature on intensity normalization
      has focused on histogram matching and other histogram mapping techniques, with
      little emphasis on normalizing images to have biologically interpretable units.
      Furthermore, there are no formalized principles or goals for the crucial
      comparability of image intensities within and across subjects. To address this,
      we propose a set of criteria necessary for the normalization of images. We
      further propose simple and robust biologically motivated normalization techniques
      for multisequence brain imaging that have the same interpretation across
      acquisitions and satisfy the proposed criteria. We compare the performance of
      different normalization methods in thousands of images of patients with
      Alzheimer's disease, hundreds of patients with multiple sclerosis, and hundreds
      of healthy subjects obtained in several different studies at dozens of imaging
      centers. 

PMID- 25379413
TI  - The effects of deefferentation without deafferentation on functional connectivity
      in patients with facial palsy.
AB  - Cerebral plasticity includes the adaptation of anatomical and functional
      connections between parts of the involved brain network. However, little is known
      about the network dynamics of these connectivity changes. This study investigates
      the impact of a pure deefferentation, without deafferentation or brain damage, on
      the functional connectivity of the brain. To investigate this issue, functional
      MRI was performed on 31 patients in the acute state of Bell's palsy (idiopathic
      peripheral facial nerve palsy). All of the patients performed a motor paradigm to
      identify seed regions involved in motor control. The functional connectivity of
      the resting state within this network of brain regions was compared to a healthy
      control group. We found decreased connectivity in patients, mainly in areas
      responsible for sensorimotor integration and supervision (SII, insula, thalamus
      and cerebellum). However, we did not find decreased connectivity in areas of the
      primary or secondary motor cortex. The decreased connectivity for the SII and the
      insula significantly correlated to the severity of the facial palsy. Our results
      indicate that a pure deefferentation leads the brain to adapt to the current
      compromised state during rest. The motor system did not make a major attempt to
      solve the sensorimotor discrepancy by modulating the motor program. 

PMID- 25379414
TI  - Cellular correlates of longitudinal diffusion tensor imaging of axonal
      degeneration following hypoxic-ischemic cerebral infarction in neonatal rats.
AB  - Ischemically damaged brain can be accompanied by secondary degeneration of
      associated axonal connections e.g. Wallerian degeneration. Diffusion tensor
      imaging (DTI) is widely used to investigate axonal injury but the cellular
      correlates of many of the degenerative changes remain speculative. We
      investigated the relationship of DTI of directly damaged cerebral cortex and
      secondary axonal degeneration in the cerebral peduncle with cellular alterations
      in pan-axonal neurofilament staining, myelination, reactive astrocytes,
      activation of microglia/macrophages and neuronal cell death. DTI measures (axial,
      radial and mean diffusivity, and fractional anisotropy (FA)) were acquired at
      hyperacute (3 h), acute (1 and 2 d) and chronic (1 and 4 week) times after
      transient cerebral hypoxia with unilateral ischemia in neonatal rats. The tissue
      pathology underlying ischemic and degenerative responses had a complex
      relationship with DTI parameters. DTI changes at hyperacute and subacute times
      were smaller in magnitude and tended to be transient and/or delayed in cerebral
      peduncle compared to cerebral cortex. In cerebral peduncle by 1 d post-insult,
      there were reductions in neurofilament staining corresponding with decreases in
      parallel diffusivity which were more sensitive than mean diffusivity in detecting
      axonal changes. Ipsilesional reductions in FA within cerebral peduncle were
      robust in detecting both early and chronic degenerative responses. At one or four
      weeks post-insult, radial diffusivity was increased ipsilaterally in the cerebral
      peduncle corresponding to pathological evidence of a lack of ontogenic
      myelination in this region. The detailed differences in progression and magnitude
      of DTI and histological changes reported provide a reference for identifying the
      potential contribution of various cellular responses to FA, and, parallel,
      radial, and mean diffusivity.

PMID- 25379415
TI  - Lateral prefrontal cortex activity during cognitive control of emotion predicts
      response to social stress in schizophrenia.
AB  - LPFC dysfunction is a well-established neural impairment in schizophrenia and is
      associated with worse symptoms. However, how LPFC activation influences symptoms
      is unclear. Previous findings in healthy individuals demonstrate that lateral
      prefrontal cortex (LPFC) activation during cognitive control of emotional
      information predicts mood and behavior in response to interpersonal conflict,
      thus impairments in these processes may contribute to symptom exacerbation in
      schizophrenia. We investigated whether schizophrenia participants show LPFC
      deficits during cognitive control of emotional information, and whether these
      LPFC deficits prospectively predict changes in mood and symptoms following real
      world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or
      schizoaffective disorder and 24 healthy controls completed the Multi-Source
      Interference Task superimposed on neutral and negative pictures. Afterwards,
      schizophrenia participants completed a 21-day online daily-diary in which they
      rated the extent to which they experienced mood and schizophrenia-spectrum
      symptoms, as well as the occurrence and response to interpersonal conflict.
      Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive
      control of task-irrelevant negative emotional information. Within schizophrenia
      participants, DLPFC activity during cognitive control of emotional information
      predicted changes in positive and negative mood on days following highly
      distressing interpersonal conflicts. Results have implications for understanding
      the specific role of LPFC in response to social stress in schizophrenia, and
      suggest that treatments targeting LPFC-mediated cognitive control of emotion
      could promote adaptive response to social stress in schizophrenia. 

PMID- 25379416
TI  - Neural compensation in adulthood following very preterm birth demonstrated during
      a visual paired associates learning task.
AB  - Very preterm birth (VPT; < 33 weeks of gestation) is associated with an increased
      risk of learning disability, which contributes to more VPT-born children
      repeating grades and underachieving in school. Learning problems associated with
      VPT birth may be caused by pathophysiological alterations in neurodevelopment
      resulting from perinatal brain insult; however, adaptive neuroplastic processes
      may subsequently occur in the developing preterm brain which ameliorate, to an
      extent, the potential sequelae of altered neurophysiology. Here, we used
      functional magnetic resonance imaging (fMRI) to compare neuronal activation in 24
      VPT individuals and 22 controls (CT) in young adulthood during a learning task
      consisting of the encoding and subsequent recognition of repeated visual paired
      associates. Structural MRI data were also collected and analysed in order to
      explore possible structure-function associations. Whilst the two groups did not
      differ in their learning ability, as demonstrated by their capacity to recognize
      previously-seen and previously-unseen visual pairs, between-group differences in
      linear patterns of Blood Oxygenation Level Dependant (BOLD) activity were
      observed across the four repeated blocks of the task for both the encoding and
      recognition conditions, suggesting that the way learning takes place differs
      between the two groups. During encoding, significant between-group differences in
      patterns of BOLD activity were seen in clusters centred on the cerebellum, the
      anterior cingulate gyrus, the midbrain/substantia nigra, medial temporal
      (including parahippocampal) gyrus and inferior and superior frontal gyri. During
      the recognition condition, significant between-group differences in patterns of
      BOLD activity were seen in clusters centred on the claustrum and the posterior
      cerebellum. Structural analysis revealed smaller grey matter volume in right
      middle temporal gyrus in VPT individuals compared to controls, however volume in
      this region was not significantly associated with functional activation. These
      results demonstrate that although cognitive task performance between VPT
      individuals and controls may be comparable on certain measures, differences in
      BOLD signal may also be evident, some of which could represent compensatory
      neural processes following VPT-related brain insult.

PMID- 25379417
TI  - Localizing ECoG electrodes on the cortical anatomy without post-implantation
      imaging.
AB  - INTRODUCTION: Electrocorticographic (ECoG) grids are placed subdurally on the
      cortex in people undergoing cortical resection to delineate eloquent cortex. ECoG
      signals have high spatial and temporal resolution and thus can be valuable for
      neuroscientific research. The value of these data is highest when they can be
      related to the cortical anatomy. Existing methods that establish this
      relationship rely either on post-implantation imaging using computed tomography
      (CT), magnetic resonance imaging (MRI) or X-Rays, or on intra-operative
      photographs. For research purposes, it is desirable to localize ECoG electrodes
      on the brain anatomy even when post-operative imaging is not available or when
      intra-operative photographs do not readily identify anatomical landmarks.
      METHODS: We developed a method to co-register ECoG electrodes to the underlying
      cortical anatomy using only a pre-operative MRI, a clinical neuronavigation
      device (such as BrainLab VectorVision), and fiducial markers. To validate our
      technique, we compared our results to data collected from six subjects who also
      had post-grid implantation imaging available. We compared the electrode
      coordinates obtained by our fiducial-based method to those obtained using
      existing methods, which are based on co-registering pre- and post-grid
      implantation images. RESULTS: Our fiducial-based method agreed with the MRI-CT
      method to within an average of 8.24 mm (mean, median = 7.10 mm) across 6 subjects
      in 3 dimensions. It showed an average discrepancy of 2.7 mm when compared to the
      results of the intra-operative photograph method in a 2D coordinate system. As
      this method does not require post-operative imaging such as CTs, our technique
      should prove useful for research in intra-operative single-stage surgery
      scenarios. To demonstrate the use of our method, we applied our method during
      real-time mapping of eloquent cortex during a single-stage surgery. The results
      demonstrated that our method can be applied intra-operatively in the absence of
      post-operative imaging to acquire ECoG signals that can be valuable for
      neuroscientific investigations.

PMID- 25379419
TI  - A white matter lesion-filling approach to improve brain tissue volume
      measurements.
AB  - Multiple sclerosis white matter (WM) lesions can affect brain tissue volume
      measurements of voxel-wise segmentation methods if these lesions are included in
      the segmentation process. Several authors have presented different techniques to
      improve brain tissue volume estimations by filling WM lesions before segmentation
      with intensities similar to those of WM. Here, we propose a new method to refill
      WM lesions, where contrary to similar approaches, lesion voxel intensities are
      replaced by random values of a normal distribution generated from the mean WM
      signal intensity of each two-dimensional slice. We test the performance of our
      method by estimating the deviation in tissue volume between a set of 30 T1-w 1.5
      T and 30 T1-w 3 T images of healthy subjects and the same images where: WM
      lesions have been previously registered and afterwards replaced their voxel
      intensities to those between gray matter (GM) and WM tissue. Tissue volume is
      computed independently using FAST and SPM8. When compared with the state-of-the
      art methods, on 1.5 T data our method yields the lowest deviation in WM between
      original and filled images, independently of the segmentation method used. It
      also performs the lowest differences in GM when FAST is used and equals to the
      best method when SPM8 is employed. On 3 T data, our method also outperforms the
      state-of-the-art methods when FAST is used while performs similar to the best
      method when SPM8 is used. The proposed technique is currently available to
      researchers as a stand-alone program and as an SPM extension.

PMID- 25379418
TI  - Links between white matter microstructure and cortisol reactivity to stress in
      early childhood: evidence for moderation by parenting.
AB  - Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol
      reactivity) may be a biological marker of risk for depression and anxiety,
      possibly even early in development. However, the structural neural correlates of
      early cortisol reactivity are not well known, although these would potentially
      inform broader models of mechanisms of risk, especially if the early environment
      further shapes these relationships. Therefore, we examined links between white
      matter architecture and young girls' cortisol reactivity and whether early
      caregiving moderated these links. We recruited 45 6-year-old girls based on
      whether they had previously shown high or low cortisol reactivity to a stress
      task at age 3. White matter integrity was assessed by calculating fractional
      anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting
      styles were measured via a standardized parent-child interaction task.
      Significant associations were found between FA in white matter regions adjacent
      to the left thalamus, the right anterior cingulate cortex, and the right superior
      frontal gyrus (all ps < .001). Further, positive early caregiving moderated the
      effect of high cortisol reactivity on white matter FA (all ps <= .05), with high
      stress reactive girls who received greater parent positive affect showing white
      matter structure more similar to that of low stress reactive girls. Results show
      associations between white matter integrity of various limbic regions of the
      brain and early cortisol reactivity to stress and provide preliminary support for
      the notion that parenting may moderate associations.

PMID- 25379420
TI  - Cerebellar pathology in Friedreich's ataxia: atrophied dentate nuclei with normal
      iron content.
AB  - BACKGROUND: In Friedreich's ataxia (FA) the genetically decreased expression of
      the mitochondrial protein frataxin leads to disturbance of the mitochondrial iron
      metabolism. Within the cerebellum the dentate nuclei (DN) are primarily affected.
      Histopathological studies show atrophy and accumulation of mitochondrial iron in
      DN. Dentate iron content has been suggested as a biomarker to measure the effects
      of siderophores/antioxidant treatment of FA. We assessed the iron content and the
      volume of DN in FA patients and controls based on ultra-high-field MRI (7 Tesla)
      images. METHODS: Fourteen FA patients (mean age 38.1 yrs) and 14 age- and gender
      matched controls participated. Multi-echo gradient echo and susceptibility
      weighted imaging (SWI) sequences were acquired on a 7 T whole-body scanner. For
      comparison SWI images were acquired on a 1.5 T MR scanner. Volumes of the DN and
      cerebellum were assessed at 7 and 1.5 T, respectively. Parametric maps of T2 and
      T2* sequences were created and proton transverse relaxation rates were estimated
      as a measure of iron content. RESULTS: In FA, the DN and the cerebellum were
      significantly smaller compared to controls. However, proton transverse relaxation
      rates of the DN were not significantly different between both groups.
      CONCLUSIONS: Applying in vivo MRI methods we could demonstrate significant
      atrophy of the DN in the presence of normal iron content. The findings suggest
      that relaxation rates are not reliable biomarkers in clinical trials evaluating
      the potential effect of FA therapy.

PMID- 25379421
TI  - Disrupted functional connectivity of the periaqueductal gray in chronic low back
      pain.
AB  - Chronic low back pain is a common neurological disorder. The periaqueductal gray
      (PAG) plays a key role in the descending modulation of pain. In this study, we
      investigated brain resting state PAG functional connectivity (FC) differences
      between patients with chronic low back pain (cLBP) in low pain or high pain
      condition and matched healthy controls (HCs). PAG seed based functional
      connectivity (FC) analysis of the functional MR imaging data was performed to
      investigate the difference among the connectivity maps in the cLBP in the low or
      high pain condition and HC groups as well as within the cLBP at differing
      endogenous back pain intensities. Results showed that FC between the PAG and the
      ventral medial prefrontal cortex (vmPFC)/rostral anterior cingulate cortex (rACC)
      increased in cLBP patients compared to matched controls. In addition, we also
      found significant negative correlations between pain ratings and PAG-vmPFC/rACC
      FC in cLBP patients after pain-inducing maneuver. The duration of cLBP was
      negatively correlated with PAG-insula and PAG-amygdala FC before pain-inducing
      maneuver in the patient group. These findings are in line with the impairments of
      the descending pain modulation reported in patients with cLBP. Our results
      provide evidence showing that cLBP patients have abnormal FC in PAG centered pain
      modulation network during rest.

PMID- 25379422
TI  - Disrupted functional connectivity of the default mode network due to acute
      vestibular deficit.
AB  - Vestibular neuritis is defined as a sudden unilateral partial failure of the
      vestibular nerve that impairs the forwarding of vestibular information from the
      labyrinth. The patient suffers from vertigo, horizontal nystagmus and postural
      instability with a tendency toward ipsilesional falls. Although vestibular
      neuritis is a common disease, the central mechanisms to compensate for the loss
      of precise vestibular information remain poorly understood. It was hypothesized
      that symptoms following acute vestibular neuritis originate from difficulties in
      the processing of diverging sensory information between the responsible brain
      networks. Accordingly an altered resting activity was shown in multiple brain
      areas of the task-positive network. Because of the known balance between the task
      positive and task-negative networks (default mode network; DMN) we hypothesize
      that also the DMN is involved. Here, we employ functional magnetic resonance
      imaging (fMRI) in the resting state to investigate changes in the functional
      connectivity between the DMN and task-positive networks, in a longitudinal design
      combined with measurements of caloric function. We demonstrate an initially
      disturbed connectedness of the DMN after vestibular neuritis. We hypothesize that
      the disturbed connectivity between the default mode network and particular parts
      of the task-positive network might be related to a sustained utilization of
      processing capacity by diverging sensory information. The current results provide
      some insights into mechanisms of central compensation following an acute
      vestibular deficit and the importance of the DMN in this disease. 

PMID- 25379423
TI  - Random Forest ensembles for detection and prediction of Alzheimer's disease with
      a good between-cohort robustness.
AB  - Computer-aided diagnosis of Alzheimer's disease (AD) is a rapidly developing
      field of neuroimaging with strong potential to be used in practice. In this
      context, assessment of models' robustness to noise and imaging protocol
      differences together with post-processing and tuning strategies are key tasks to
      be addressed in order to move towards successful clinical applications. In this
      study, we investigated the efficacy of Random Forest classifiers trained using
      different structural MRI measures, with and without neuroanatomical constraints
      in the detection and prediction of AD in terms of accuracy and between-cohort
      robustness. From The ADNI database, 185 AD, and 225 healthy controls (HC) were
      randomly split into training and testing datasets. 165 subjects with mild
      cognitive impairment (MCI) were distributed according to the month of conversion
      to dementia (4-year follow-up). Structural 1.5-T MRI-scans were processed using
      Freesurfer segmentation and cortical reconstruction. Using the resulting output,
      AD/HC classifiers were trained. Training included model tuning and performance
      assessment using out-of-bag estimation. Subsequently the classifiers were
      validated on the AD/HC test set and for the ability to predict MCI-to-AD
      conversion. Models' between-cohort robustness was additionally assessed using the
      AddNeuroMed dataset acquired with harmonized clinical and imaging protocols. In
      the ADNI set, the best AD/HC sensitivity/specificity (88.6%/92.0% - test set) was
      achieved by combining cortical thickness and volumetric measures. The Random
      Forest model resulted in significantly higher accuracy compared to the reference
      classifier (linear Support Vector Machine). The models trained using parcelled
      and high-dimensional (HD) input demonstrated equivalent performance, but the
      former was more effective in terms of computation/memory and time costs. The
      sensitivity/specificity for detecting MCI-to-AD conversion (but not AD/HC
      classification performance) was further improved from 79.5%/75%-83.3%/81.3% by a
      combination of morphometric measurements with ApoE-genotype and demographics
      (age, sex, education). When applied to the independent AddNeuroMed cohort, the
      best ADNI models produced equivalent performance without substantial accuracy
      drop, suggesting good robustness sufficient for future clinical implementation.

PMID- 25379424
TI  - Measurement of brain perfusion in newborns: pulsed arterial spin labeling (PASL)
      versus pseudo-continuous arterial spin labeling (pCASL).
AB  - BACKGROUND: Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by
      magnetic resonance imaging (MRI) has been shown to be useful for identifying
      asphyxiated newborns at risk of developing brain injury, whether or not
      therapeutic hypothermia was administered. However, this technique has been only
      rarely used in newborns until now, because of the challenges to obtain sufficient
      signal-to-noise ratio (SNR) and spatial resolution in newborns. OBJECTIVE: To
      compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin
      labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL])
      to assess brain perfusion in asphyxiated newborns treated with therapeutic
      hypothermia and in healthy newborns. DESIGN/METHODS: We conducted a prospective
      cohort study of term asphyxiated newborns meeting the criteria for therapeutic
      hypothermia; four additional healthy term newborns were also included as
      controls. Each of the enrolled newborns was scanned at least once during the
      first month of life. Each MRI scan included conventional anatomical imaging, as
      well as PASL and pCASL PWI-MRI. Control and labeled images were registered
      separately to reduce the effect of motion artifacts. For each scan, the axial
      slice at the level of the basal ganglia was used for comparisons. Each scan was
      scored for its image quality. Quantification of whole-slice cerebral blood flow
      (CBF) was done afterwards using previously described formulas. RESULTS: A total
      number of 61 concomitant PASL and pCASL scans were obtained in nineteen
      asphyxiated newborns treated with therapeutic hypothermia and four healthy
      newborns. After discarding the scans with very poor image quality, 75% (46/61)
      remained for comparison between the two ASL methods. pCASL images presented a
      significantly superior image quality score compared to PASL images (p < 0.0001).
      Strong correlation was found between the CBF measured by PASL and pCASL (r =
      0.61, p < 0.0001). CONCLUSION: This study demonstrates that both ASL methods are
      feasible to assess brain perfusion in healthy and sick newborns. However, pCASL
      might be a better choice over PASL in newborns, as pCASL perfusion maps had a
      superior image quality that allowed a more detailed identification of the
      different brain structures.

PMID- 25379425
TI  - Multimodal assessments of the hippocampal formation in schizophrenia and bipolar
      disorder: evidences from neurobehavioral measures and functional and structural
      MRI.
AB  - A potential clinical and etiological overlap between schizophrenia (SZ) and
      bipolar disorder (BD) has long been a subject of discussion. Imaging studies
      imply functional and structural alterations of the hippocampus in both diseases.
      Thus, imaging this core memory region could provide insight into the
      pathophysiology of these disorders and the associated cognitive deficits. To
      examine possible shared alterations in the hippocampus, we conducted a multi
      modal assessment, including functional and structural imaging as well as
      neurobehavioral measures of memory performance in BD and SZ patients compared
      with healthy controls. We assessed episodic memory performance, using tests of
      verbal and visual learning (HVLT, BVMT) in three groups of participants: BD
      patients (n = 21), SZ patients (n = 21) and matched (age, gender, education)
      healthy control subjects (n = 21). In addition, we examined hippocampal resting
      state functional connectivity, hippocampal volume using voxel-based morphometry
      (VBM) and fibre integrity of hippocampal connections using diffusion tensor
      imaging (DTI). We found memory deficits, changes in functional connectivity
      within the hippocampal network as well as volumetric reductions and altered white
      matter fibre integrity across patient groups in comparison with controls.
      However, SZ patients when directly compared with BD patients were more severely
      affected in several of the assessed parameters (verbal learning, left hippocampal
      volumes, mean diffusivity of bilateral cingulum and right uncinated fasciculus).
      The results of our study suggest a graded expression of verbal learning deficits
      accompanied by structural alterations within the hippocampus in BD patients and
      SZ patients, with SZ patients being more strongly affected. Our findings imply
      that these two disorders may share some common pathophysiological mechanisms. The
      results could thus help to further advance and integrate current
      pathophysiological models of SZ and BD.

PMID- 25379426
TI  - Temporal-lobe morphology differs between healthy adolescents and those with early
      onset of depression.
AB  - Major depressive disorder (MDD) has previously been linked to structural changes
      in several brain regions, particularly in the medial temporal lobes (Bellani,
      Baiano, Brambilla, 2010; Bellani, Baiano, Brambilla, 2011). This has been
      determined using voxel-based morphometry, segmentation algorithms, and analysis
      of shape deformations (Bell-McGinty et al., 2002; Bergouignan et al., 2009;
      Posener et al., 2003; Vasic et al., 2008; Zhao et al., 2008): these are methods
      in which information related to the shape and the pose (the size, and anatomical
      position and orientation) of structures is lost. Here, we incorporate information
      about shape and pose to measure structural deformation in adolescents and young
      adults with and without depression (as measured using the Beck Depression
      Inventory and Diagnostic and Statistical Manual of Mental Disorders criteria). As
      a hypothesis-generating study, a significance level of p < 0.05, uncorrected for
      multiple comparisons, was used, so that subtle morphological differences in brain
      structures between adolescent depressed individuals and control participants
      could be identified. We focus on changes in cortical and subcortical temporal
      structures, and use a multi-object statistical pose and shape model to analyze
      imaging data from 16 females (aged 16-21) and 3 males (aged 18) with early-onset
      MDD, and 25 female and 1 male normal control participants, drawn from the same
      age range. The hippocampus, parahippocampal gyrus, putamen, and superior,
      inferior and middle temporal gyri in both hemispheres of the brain were
      automatically segmented using the LONI Probabilistic Brain Atlas (Shattuck et
      al., 2008) in MNI space. Points on the surface of each structure in the atlas
      were extracted and warped to each participant's structural MRI. These surface
      points were analyzed to extract the pose and shape features. Pose differences
      were detected between the two groups, particularly in the left and right
      putamina, right hippocampus, and left and right inferior temporal gyri. Shape
      differences were detected between the two groups, particularly in the left
      hippocampus and in the left and right parahippocampal gyri. Furthermore, pose
      measures were significantly correlated with BDI score across the whole (clinical
      and control) sample. Since the clinical participants were experiencing their very
      first episodes of MDD, morphological alteration in the medial temporal lobe
      appears to be an early sign of MDD, and is unlikely to result from treatment with
      antidepressants. Pose and shape measures of morphology, which are not usually
      analyzed in neuromorphometric studies, appear to be sensitive to depressive
      symptomatology.

PMID- 25379427
TI  - Changing facial affect recognition in schizophrenia: effects of training on brain
      dynamics.
AB  - Deficits in social cognition including facial affect recognition and their
      detrimental effects on functional outcome are well established in schizophrenia.
      Structured training can have substantial effects on social cognitive measures
      including facial affect recognition. Elucidating training effects on cortical
      mechanisms involved in facial affect recognition may identify causes of
      dysfunctional facial affect recognition in schizophrenia and foster remediation
      strategies. In the present study, 57 schizophrenia patients were randomly
      assigned to (a) computer-based facial affect training that focused on affect
      discrimination and working memory in 20 daily 1-hour sessions, (b) similarly
      intense, targeted cognitive training on auditory-verbal discrimination and
      working memory, or (c) treatment as usual. Neuromagnetic activity was measured
      before and after training during a dynamic facial affect recognition task (5 s
      videos showing human faces gradually changing from neutral to fear or to happy
      expressions). Effects on 10-13 Hz (alpha) power during the transition from
      neutral to emotional expressions were assessed via MEG based on previous findings
      that alpha power increase is related to facial affect recognition and is smaller
      in schizophrenia than in healthy subjects. Targeted affect training improved
      overt performance on the training tasks. Moreover, alpha power increase during
      the dynamic facial affect recognition task was larger after affect training than
      after treatment-as-usual, though similar to that after targeted perceptual
      cognitive training, indicating somewhat nonspecific benefits. Alpha power
      modulation was unrelated to general neuropsychological test performance, which
      improved in all groups. Results suggest that specific neural processes supporting
      facial affect recognition, evident in oscillatory phenomena, are modifiable. This
      should be considered when developing remediation strategies targeting social
      cognition in schizophrenia.

PMID- 25379428
TI  - Correlation between brain volume change and T2 relaxation time induced by
      dehydration and rehydration: implications for monitoring atrophy in clinical
      studies.
AB  - Brain volume change measured from magnetic resonance imaging (MRI) provides a
      widely used and useful in vivo measure of irreversible tissue loss. These
      measurements, however, can be influenced by reversible factors such as shifts in
      brain water content. Given the strong effect of water on T2 relaxation, we
      investigated whether an estimate of T2 relaxation time would correlate with brain
      volume changes induced by physiologically manipulating hydration status. We used
      a clinically feasible estimate of T2 ("pseudo-T2") computed from a dual turbo
      spin-echo MRI sequence and correlated pseudo-T2 changes to percent brain volume
      changes in 12 healthy subjects after dehydration overnight (16-hour thirsting)
      and rehydration (drinking 1.5 L of water). We found that the brain volume
      significantly increased between the dehydrated and rehydrated states (mean brain
      volume change = 0.36%, p = 0.0001) but did not change significantly during the
      dehydration interval (mean brain volume change = 0.04%, p = 0.57). The changes in
      brain volume and pseudo-T2 significantly correlated with each other, with
      marginal and conditional correlations (R (2)) of 0.44 and 0.65, respectively. Our
      results show that pseudo-T2 may be used in conjunction with the measures of brain
      volume to distinguish reversible water fluctuations and irreversible brain tissue
      loss (atrophy) and to investigate disease mechanisms related to neuro
      inflammation, e.g., in multiple sclerosis, where edema-related water fluctuations
      may occur with disease activity and anti-inflammatory treatment.

PMID- 25379429
TI  - Abnormal synchrony and effective connectivity in patients with schizophrenia and
      auditory hallucinations.
AB  - Auditory hallucinations (AH) are the most frequent positive symptoms in patients
      with schizophrenia. Hallucinations have been related to emotional processing
      disturbances, altered functional connectivity and effective connectivity
      deficits. Previously, we observed that, compared to healthy controls, the limbic
      network responses of patients with auditory hallucinations differed when the
      subjects were listening to emotionally charged words. We aimed to compare the
      synchrony patterns and effective connectivity of task-related networks between
      schizophrenia patients with and without AH and healthy controls. Schizophrenia
      patients with AH (n = 27) and without AH (n = 14) were compared with healthy
      participants (n = 31). We examined functional connectivity by analyzing
      correlations and cross-correlations among previously detected independent
      component analysis time courses. Granger causality was used to infer the
      information flow direction in the brain regions. The results demonstrate that the
      patterns of cortico-cortical functional synchrony differentiated the patients
      with AH from the patients without AH and from the healthy participants.
      Additionally, Granger-causal relationships between the networks clearly
      differentiated the groups. In the patients with AH, the principal causal source
      was an occipital-cerebellar component, versus a temporal component in the
      patients without AH and the healthy controls. These data indicate that an
      anomalous process of neural connectivity exists when patients with AH process
      emotional auditory stimuli. Additionally, a central role is suggested for the
      cerebellum in processing emotional stimuli in patients with persistent AH.

PMID- 25379430
TI  - Preterm birth and structural brain alterations in early adulthood.
AB  - Alterations in cortical development and impaired neurodevelopmental outcomes have
      been described following very preterm (VPT) birth in childhood and adolescence,
      but only a few studies to date have investigated grey matter (GM) and white
      matter (WM) maturation in VPT samples in early adult life. Using voxel-based
      morphometry (VBM) we studied regional GM and WM volumes in 68 VPT-born
      individuals (mean gestational age 30 weeks) and 43 term-born controls aged 19-20
      years, and their association with cognitive outcomes (Hayling Sentence Completion
      Test, Controlled Oral Word Association Test, Visual Reproduction test of the
      Wechsler Memory Scale-Revised) and gestational age. Structural MRI data were
      obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with
      a customized study-specific template. Similarly to results obtained at adolescent
      assessment, VPT young adults compared to controls demonstrated reduced GM volume
      in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and
      putamen. Increases in GM volume were noted in medial/anterior frontal gyrus.
      Smaller subcortical WM volume in the VPT group was observed in temporal, parietal
      and frontal regions, and in a cluster centred on posterior corpus
      callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in
      posterior brain regions, in areas beneath the parahippocampal and occipital gyri
      and in cerebellum. Gestational age was associated with GM and WM volumes in areas
      where VPT individuals demonstrated GM and WM volumetric alterations, especially
      in temporal, parietal and occipital regions. VPT participants scored lower than
      controls on measures of IQ, executive function and non-verbal memory. When
      investigating GM and WM alterations and cognitive outcome scores, subcortical WM
      volume in an area beneath the left inferior frontal gyrus accounted for 14% of
      the variance of full-scale IQ (F = 12.9, p < 0.0001). WM volume in posterior
      corpus callosum/thalamus/fornix and GM volume in temporal gyri bilaterally,
      accounted for 21% of the variance of executive function (F = 9.9, p < 0.0001) and
      WM in the posterior corpus callosum/thalamus/fornix alone accounted for 17% of
      the variance of total non-verbal memory scores (F = 9.9, p < 0.0001). These
      results reveal that VPT birth continues to be associated with altered structural
      brain anatomy in early adult life, although it remains to be ascertained whether
      these changes reflect neurodevelopmental delays or long lasting structural
      alterations due to prematurity. GM and WM alterations correlate with length of
      gestation and mediate cognitive outcome.

PMID- 25379431
TI  - Acute neuropharmacological effects of atomoxetine on inhibitory control in ADHD
      children: a fNIRS study.
AB  - The object of the current study is to explore the neural substrate for effects of
      atomoxetine (ATX) on inhibitory control in school-aged children with attention
      deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy
      (fNIRS). We monitored the oxy-hemoglobin signal changes of sixteen ADHD children
      (6-14 years old) performing a go/no-go task before and 1.5 h after ATX or placebo
      administration, in a randomized, double-blind, placebo-controlled, crossover
      design. Sixteen age- and gender-matched normal controls without ATX
      administration were also monitored. In the control subjects, the go/no-go task
      recruited the right inferior and middle prefrontal gyri (IFG/MFG), and this
      activation was absent in pre-medicated ADHD children. The reduction of right
      IFG/MFG activation was acutely normalized after ATX administration but not
      placebo administration in ADHD children. These results are reminiscent of the
      neuropharmacological effects of methylphenidate to up-regulate reduced right
      IFG/MFG function in ADHD children during inhibitory tasks. As with
      methylphenidate, activation in the IFG/MFG could serve as an objective neuro
      functional biomarker to indicate the effects of ATX on inhibitory control in ADHD
      children. This promising technique will enhance early clinical diagnosis and
      treatment of ADHD in children, especially in those with a
      hyperactivity/impulsivity phenotype.

PMID- 25379432
TI  - Reduced beta band connectivity during number estimation in autism.
AB  - Recent evidence suggests that disruption of integrative processes in sensation
      and perception may play a critical role in cognitive and behavioural
      atypicalities characteristic of ASD. In line with this, ASD is associated with
      altered structural and functional brain connectivity and atypical patterns of
      inter-regional communication which have been proposed to contribute to cognitive
      difficulties prevalent in this group. The present MEG study used atlas-guided
      source space analysis of inter-regional phase synchronization in ASD
      participants, as well as matched typically developing controls, during a dot
      number estimation task. This task included stimuli with globally integrated forms
      (animal shapes) as well as randomly-shaped stimuli which lacked a coherent global
      pattern. Early task-dependent increases in inter-regional phase synchrony in
      theta, alpha and beta frequency bands were observed. Reduced long-range beta-band
      phase synchronization was found in participants with ASD at 70-145 ms during
      presentation of globally coherent dot patterns. This early reduction in task
      dependent inter-regional connectivity encompassed numerous areas including
      occipital, parietal, temporal, and frontal lobe regions. These results provide
      the first evidence for inter-regional phase synchronization during numerosity
      estimation, as well as its alteration in ASD, and suggest that problems with
      communication among brain areas may contribute to difficulties with integrative
      processes relevant to extraction of meaningful 'Gestalt' features in this
      population.

PMID- 25379433
TI  - The Default Mode Network is functionally and structurally disrupted in amnestic
      mild cognitive impairment - a bimodal MEG-DTI study.
AB  - Over the past years, several studies on Mild Cognitive Impairment (MCI) and
      Alzheimer's disease (AD) have reported Default Mode Network (DMN) deficits. This
      network is attracting increasing interest in the AD community, as it seems to
      play an important role in cognitive functioning and in beta amyloid deposition.
      Attention has been particularly drawn to how different DMN regions are connected
      using functional or structural connectivity. To this end, most studies have used
      functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET)
      or Diffusion Tensor Imaging (DTI). In this study we evaluated (1) functional
      connectivity from resting state magnetoencephalography (MEG) and (2) structural
      connectivity from DTI in 26 MCI patients and 31 age-matched controls. Compared to
      controls, the DMN in the MCI group was functionally disrupted in the alpha band,
      while no differences were found for delta, theta, beta and gamma frequency bands.
      In addition, structural disconnection could be assessed through a decreased
      fractional anisotropy along tracts connecting different DMN regions. This
      suggests that the DMN functional and anatomical disconnection could represent a
      core feature of MCI. 

PMID- 25379434
TI  - Aberrant spontaneous brain activity in chronic tinnitus patients revealed by
      resting-state functional MRI.
AB  - OBJECTIVE: The neural mechanisms that give rise to the phantom sound of tinnitus
      are poorly understood. This study aims to investigate whether aberrant
      spontaneous brain activity exists in chronic tinnitus patients using resting
      state functional magnetic resonance imaging (fMRI) technique. MATERIALS AND
      METHODS: A total of 31 patients with chronic tinnitus patients and 32 healthy age
      , sex-, and education-matched healthy controls were prospectively examined. Both
      groups had normal hearing thresholds. We calculated the amplitude of low
      frequency fluctuations (ALFFs) of fMRI signals to measure spontaneous neuronal
      activity and detect the relationship between fMRI information and clinical data
      of tinnitus. RESULTS: Compared with healthy controls, we observed significant
      increased ALFF within several selected regions including the right middle
      temporal gyrus (MTG), right superior frontal gyrus (SFG), and right angular
      gyrus; decreased ALFF was detected in the left cuneus, right middle occipital
      gyrus and bilateral thalamus. Moreover, tinnitus distress correlated positively
      with increased ALFF in right MTG and right SFG; tinnitus duration correlated
      positively with higher ALFF values in right SFG. CONCLUSIONS: The present study
      confirms that chronic tinnitus patients have aberrant ALFF in many brain regions,
      which is associated with specific clinical tinnitus characteristics. ALFF
      disturbance in specific brain regions might be used to identify the neuro
      pathophysiological mechanisms in chronic tinnitus patients.

PMID- 25379435
TI  - Multivariate neuroanatomical classification of cognitive subtypes in
      schizophrenia: a support vector machine learning approach.
AB  - Heterogeneity in the structural brain abnormalities associated with schizophrenia
      has made identification of reliable neuroanatomical markers of the disease
      difficult. The use of more homogenous clinical phenotypes may improve the
      accuracy of predicting psychotic disorder/s on the basis of observable brain
      disturbances. Here we investigate the utility of cognitive subtypes of
      schizophrenia - 'cognitive deficit' and 'cognitively spared' - in determining
      whether multivariate patterns of volumetric brain differences can accurately
      discriminate these clinical subtypes from healthy controls, and from each other.
      We applied support vector machine classification to grey- and white-matter volume
      data from 126 schizophrenia patients previously allocated to the cognitive spared
      subtype, 74 cognitive deficit schizophrenia patients, and 134 healthy controls.
      Using this method, cognitive subtypes were distinguished from healthy controls
      with up to 72% accuracy. Cross-validation analyses between subtypes achieved an
      accuracy of 71%, suggesting that some common neuroanatomical patterns distinguish
      both subtypes from healthy controls. Notably, cognitive subtypes were best
      distinguished from one another when the sample was stratified by sex prior to
      classification analysis: cognitive subtype classification accuracy was relatively
      low (<60%) without stratification, and increased to 83% for females with sex
      stratification. Distinct neuroanatomical patterns predicted cognitive subtype
      status in each sex: sex-specific multivariate patterns did not predict cognitive
      subtype status in the other sex above chance, and weight map analyses
      demonstrated negative correlations between the spatial patterns of weights
      underlying classification for each sex. These results suggest that in typical
      mixed-sex samples of schizophrenia patients, the volumetric brain differences
      between cognitive subtypes are relatively minor in contrast to the large common
      disease-associated changes. Volumetric differences that distinguish between
      cognitive subtypes on a case-by-case basis appear to occur in a sex-specific
      manner that is consistent with previous evidence of disrupted relationships
      between brain structure and cognition in male, but not female, schizophrenia
      patients. Consideration of sex-specific differences in brain organization is thus
      likely to assist future attempts to distinguish subgroups of schizophrenia
      patients on the basis of neuroanatomical features. 

PMID- 25379436
TI  - Magnetization transfer ratio recovery in new lesions decreases during adolescence
      in pediatric-onset multiple sclerosis patients.
AB  - Children and adolescents diagnosed with multiple sclerosis rarely accrue physical
      disability early in their disease. This could be explained by greater
      remyelination in children, a capacity that may be lost in adolescence or early
      adulthood. Magnetization transfer ratio (MTR) MRI can be used to quantify changes
      in myelin in MS. We used serial MTR imaging and longitudinal random effects
      analysis to quantify recovery of MTR in acute lesions and to evaluate MTR changes
      in normal-appearing tissue in 19 adolescent MS patients. Our objective was to
      determine whether younger adolescents have a greater capacity for remyelination
      and whether this decreases as patients approach adulthood. We detected a
      significant decrease in MTR recovery between ages 16 and 20 years (p = 0.023),
      with older subjects approaching typical recovery levels for adult-onset MS. MTR
      recovery in acute MS lesions decreases with age in adolescents, suggesting loss
      of remyelination capacity. This may be related to the conclusion of primary
      myelination or other developmental factors.

PMID- 25379437
TI  - Insula and striatum activity in effort-related monetary reward processing in
      gambling disorder: the role of depressive symptomatology.
AB  - The neurobiological underpinnings of effort-related monetary reward processing of
      gambling disorder have not been previously studied. To date neuroimaging studies
      lack in large sample sizes and as a consequence less attention has been given to
      brain reward processing that could potentially be attributed to comorbid
      conditions such as depressive mood state. We assessed monetary reward processing
      using an effort-dependent task during 3 tesla functional magnetic resonance
      imaging. We investigated a large sample of male, right-handed, slot-machine
      playing disordered gamblers (DGs; N = 80) as well as age- and smoking-matched
      male healthy controls (HCs; N = 89). Depressive symptoms were assessed using the
      Beck Depression Inventory (BDI). DGs and HCs were divided into subgroups ("high"
      and "low") based on their BDI scores. Effort-related monetary reward processing
      did not differ between the complete groups of HCs and DGs. Brain activation
      during receipt of monetary reward though revealed a significant Group * BDI
      interaction: DGs with higher BDI scores compared to DGs with lower BDI scores
      showed greater brain activity in the right insula cortex and dorsal striatum
      while no differences were observed for HCs with higher versus lower BDI scores.
      Our results suggest that effort-related aspects of monetary motivation, i.e. when
      monetary output is tied to performance, are not altered in DG. Additionally, our
      findings strengthen the need for subgroup comparisons in future investigations of
      the disorder as part of a personalized medicine approach.

PMID- 25379438
TI  - Resting state connectivity correlates with drug and placebo response in
      fibromyalgia patients.
AB  - Fibromyalgia is a chronic pain syndrome characterized by widespread pain,
      fatigue, and memory and mood disturbances. Despite advances in our understanding
      of the underlying pathophysiology, treatment is often challenging. New research
      indicates that changes in functional connectivity between brain regions, as can
      be measured by magnetic resonance imaging (fcMRI) of the resting state, may
      underlie the pathogenesis of this and other chronic pain states. As such, this
      parameter may be able to be used to monitor changes in brain function associated
      with pharmacological treatment, and might also be able to predict treatment
      response. We performed a resting state fcMRI trial using a randomized, placebo
      controlled, cross-over design to investigate mechanisms of action of milnacipran
      (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in
      fibromyalgia patients. Our aim was to identify functional connectivity patterns
      at baseline that would differentially predict treatment response to MLN as
      compared to placebo. Since preclinical studies of MLN suggest that this
      medication works by augmenting antinociceptive processes, we specifically
      investigated brain regions known to be involved in pain inhibition. 15
      fibromyalgia patients completed the study, consisting of 6 weeks of drug and
      placebo intake (order counterbalanced) with an interspersed 2 week wash out
      period. As a main finding we report that reductions in clinical pain scores
      during MLN were associated with decreased functional connectivity between pro
      nociceptive regions and antinociceptive pain regions at baseline, specifically
      between the rostral part of the anterior cingulate cortex (ACC) and the insular
      cortex (IC), as well as between the periaqueductal gray (PAG) and the IC:
      patients with lower preexisting functional connectivity had the greatest
      reduction in clinical pain. This pattern was not observed for the placebo period.
      However a more robust placebo response was associated with lower baseline
      functional connectivity between the ACC and the dorsolateral prefrontal cortex.
      This study indicates that ACC-IC connectivity might play a role in the mechanism
      of action of MLN, and perhaps more importantly fcMRI might be a useful tool to
      predict pharmacological treatment response.

PMID- 25379439
TI  - Assessment of blood-brain barrier disruption using dynamic contrast-enhanced MRI.
      A systematic review.
AB  - There is increasing recognition of the importance of blood-brain barrier (BBB)
      disruption in aging, dementia, stroke and multiple sclerosis in addition to more
      commonly-studied pathologies such as tumors. Dynamic contrast-enhanced MRI (DCE
      MRI) is a method for studying BBB disruption in vivo. We review pathologies
      studied, scanning protocols and data analysis procedures to determine the range
      of available methods and their suitability to different pathologies. We
      systematically review the existing literature up to February 2014, seeking
      studies that assessed BBB integrity using T1-weighted DCE-MRI techniques in
      animals and humans in normal or abnormal brain tissues. The literature search
      provided 70 studies that were eligible for inclusion, involving 417 animals and
      1564 human subjects in total. The pathologies most studied are intracranial
      neoplasms and acute ischemic strokes. There are large variations in the type of
      DCE-MRI sequence, the imaging protocols and the contrast agents used. Moreover,
      studies use a variety of different methods for data analysis, mainly based on
      model-free measurements and on the Patlak and Tofts models. Consequently,
      estimated K (Trans) values varied widely. In conclusion, DCE-MRI is shown to
      provide valuable information in a large variety of applications, ranging from
      common applications, such as grading of primary brain tumors, to more recent
      applications, such as assessment of subtle BBB dysfunction in Alzheimer's
      disease. Further research is required in order to establish consensus-based
      recommendations for data acquisition and analysis and, hence, improve inter-study
      comparability and promote wider use of DCE-MRI. 

PMID- 25379440
TI  - Functional and structural changes in the brain associated with the increase in
      muscle sympathetic nerve activity in obstructive sleep apnoea.
AB  - Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with
      obstructive sleep apnoea (OSA) during daytime wakefulness, leading to
      hypertension, but the underlying mechanisms are poorly understood. By recording
      MSNA concurrently with functional Magnetic Resonance Imaging (fMRI) of the brain
      we aimed to identify the central processes responsible for the
      sympathoexcitation. Spontaneous fluctuations in MSNA were recorded via tungsten
      microelectrodes inserted percutaneously into the common peroneal nerve in 17 OSA
      patients and 15 healthy controls lying in a 3 T MRI scanner. Blood Oxygen Level
      Dependent (BOLD) contrast gradient echo, echo-planar images were continuously
      collected in a 4 s ON, 4 s OFF (200 volumes) sampling protocol. Fluctuations in
      BOLD signal intensity covaried with the intensity of the concurrently recorded
      bursts of MSNA. In both groups there was a positive correlation between MSNA and
      signal intensity in the left and right insulae, dorsolateral prefrontal cortex
      (dlPFC), dorsal precuneus, sensorimotor cortex and posterior temporal cortex, and
      the right mid-cingulate cortex and hypothalamus. In OSA the left and right dlPFC,
      medial PFC (mPFC), dorsal precuneus, anterior cingulate cortex, retrosplenial
      cortex and caudate nucleus showed augmented signal changes compared with
      controls, while the right hippocampus/parahippocampus signal intensity decreased
      in controls but did not change in the OSA subjects. In addition, there were
      significant increases in grey matter volume in the left mid-insula, the right
      insula, left and right primary motor cortices, left premotor cortex, left
      hippocampus and within the brainstem and cerebellum, and significant decreases in
      the mPFC, occipital lobe, right posterior cingulate cortex, left cerebellar
      cortex and the left and right amygdala in OSA, but there was no overlap between
      these structural changes and the functional changes in OSA. These data suggest
      that the elevated muscle vasoconstrictor drive in OSA may result from functional
      changes within these brain regions, which are known to be directly or indirectly
      involved in the modulation of sympathetic outflow via the brainstem. That there
      was no overlap in the structural and functional changes suggests that asphyxic
      damage due to repeated episodes of nocturnal obstructive apnoea is not the main
      cause of the sympathoexcitation.

PMID- 25379441
TI  - Novel ThickNet features for the discrimination of amnestic MCI subtypes.
AB  - BACKGROUND: Amnestic mild cognitive impairment (aMCI) is considered to be a
      transitional stage between healthy aging and Alzheimer's disease (AD), and
      consists of two subtypes: single-domain aMCI (sd-aMCI) and multi-domain aMCI (md
      aMCI). Individuals with md-aMCI are found to exhibit higher risk of conversion to
      AD. Accurate discrimination among aMCI subtypes (sd- or md-aMCI) and controls
      could assist in predicting future decline. METHODS: We apply our novel thickness
      network (ThickNet) features to discriminate md-aMCI from healthy controls (NC).
      ThickNet features are extracted from the properties of a graph constructed from
      inter-regional co-variation of cortical thickness. We fuse these ThickNet
      features using multiple kernel learning to form a composite classifier. We apply
      the proposed ThickNet classifier to discriminate between md-aMCI and NC, sd-aMCI
      and NC and; and also between sd-aMCI and md-aMCI, using baseline T1 MR scans from
      the Sydney Memory and Ageing Study. RESULTS: ThickNet classifier achieved an area
      under curve (AUC) of 0.74, with 70% sensitivity and 69% specificity in
      discriminating md-aMCI from healthy controls. The same classifier resulted in AUC
      = 0.67 and 0.67 for sd-aMCI/NC and sd-aMCI/md-aMCI classification experiments
      respectively. CONCLUSIONS: The proposed ThickNet classifier demonstrated
      potential for discriminating md-aMCI from controls, and in discriminating sd-aMCI
      from md-aMCI, using cortical features from baseline MRI scan alone. Use of the
      proposed novel ThickNet features demonstrates significant improvements over
      previous experiments using cortical thickness alone. This result may offer the
      possibility of early detection of Alzheimer's disease via improved discrimination
      of aMCI subtypes.

PMID- 25379442
TI  - Cerebellar language mapping and cerebral language dominance in pediatric epilepsy
      surgery patients.
AB  - OBJECTIVE: Children with epilepsy often have reorganization of language networks
      and abnormal brain anatomy, making determination of language lateralization
      difficult. We characterized the proportion and distribution of language task
      activation in the cerebellum to determine the relationship to cerebral language
      lateralization. METHODS: Forty-six pediatric epilepsy surgery candidates (aged 7
      19 years) completed an fMRI auditory semantic decision language task.
      Distribution of activated voxels and language laterality indices were computed
      using: (a) Broca's and Wernicke's areas and their right cerebral homologues; and
      (b) left and right cerebellar hemispheres. Language task activation was
      anatomically localized in the cerebellum. RESULTS: Lateralized language task
      activation in either cerebral hemisphere was highly correlated with lateralized
      language task activation in the contralateral cerebellar hemisphere (Broca vs.
      cerebellar: rho = -0.54, p < 0.01). Cerebellar language activation was located
      within Crus I/II, areas previously implicated in non-motor functional networks.
      CONCLUSIONS: Cerebellar language activation occurs in homologous regions of Crus
      I/II contralateral to cerebral language activation in patients with both right
      and left cerebral language dominance. Cerebellar language laterality could
      contribute to comprehensive pre-operative evaluation of language lateralization
      in pediatric epilepsy surgery patients. Our data suggest that patients with
      atypical cerebellar language activation are at risk for having atypical cerebral
      language organization.

PMID- 25379443
TI  - Reduced cortical thickness associated with visceral fat and BMI.
AB  - Structural brain imaging studies have shown that obesity is associated with
      widespread reductions in gray matter (GM) volume. Although the body mass index
      (BMI) is an easily accessible anthropometric measure, substantial health problems
      are more related to specific body fat compartments, like visceral adipose tissue
      (VAT). We investigated cortical thickness measures in a group of 72 healthy
      subjects (BMI range 20-35 kg/m(2), age range 19-50 years). Multiple regression
      analyses were performed using VAT and BMI as predictors and age, gender, total
      surface area and education as confounds. BMI and VAT were independently
      associated with reductions in cortical thickness in clusters comprising the left
      lateral occipital area, the left inferior temporal cortex, and the left
      precentral and inferior parietal area, while the right insula, the left fusiform
      gyrus and the right inferior temporal area showed a negative correlation with VAT
      only. In addition, we could show significant reductions in cortical thickness
      with increasing VAT adjusted for BMI in the left temporal cortex. We were able to
      detect widespread cortical thinning in a young to middle-aged population related
      to BMI and VAT; these findings show close resemblance to studies focusing on GM
      volume differences in diabetic patients. This may point to the influence of VAT
      related adverse effects, like low-grade inflammation, as a potentially harmful
      factor on brain integrity already in individuals at risk of developing diabetes,
      metabolic syndromes and arteriosclerosis.

PMID- 25379444
TI  - MRI correlates of disability progression in patients with CIS over 48 months.
AB  - BACKGROUND: Gray matter (GM) and white matter (WM) pathology has an important
      role in disease progression of multiple sclerosis (MS). OBJECTIVES: To
      investigate the association between the development of GM and WM pathology and
      clinical disease progression in patients with clinically isolated syndrome (CIS).
      METHODS: This prospective, observational, 48-month follow-up study examined 210
      CIS patients treated with 30 ug of intramuscular interferon beta-1a once a week.
      MRI and clinical assessments were performed at baseline, 6, 12, 24, 36 and 48
      months. Associations between clinical worsening [24-weeks sustained disability
      progression (SDP) and occurrence of a second clinical attack] and longitudinal
      changes in lesion accumulation and brain atrophy progression were investigated by
      a mixed-effect model analysis after correction for multiple comparisons. RESULTS:
      SDP was observed in 32 (15.2%) CIS patients, while 146 (69.5%) were stable and 32
      (15.2%) showed sustained disability improvement. 112 CIS patients (53.3%)
      developed clinically definite MS (CDMS). CIS patients who developed SDP showed
      increased lateral ventricle volume (p < .001), and decreased GM (p = .011) and
      cortical (p = .001) volumes compared to patients who remained stable or improved
      in disability. Converters to CDMS showed an increased rate of accumulation of
      number of new/enlarging T2 lesions (p < .001), decreased whole brain (p = .007)
      and increased lateral ventricle (p = .025) volumes. CONCLUSIONS: Development of
      GM pathology and LVV enlargement are associated with SDP. Conversion to CDMS in
      patients with CIS over 48 months is dependent on the accumulation of new lesions,
      LVV enlargement and whole brain atrophy progression.

PMID- 25379445
TI  - The circuitry of abulia: insights from functional connectivity MRI.
AB  - BACKGROUND: Functional imaging and lesion studies have associated willed behavior
      with the anterior cingulate cortex (ACC). Abulia is a syndrome characterized by
      apathy and deficiency of motivated behavior. Abulia is most frequently associated
      with ACC damage, but also occurs following damage to subcortical nuclei
      (striatum, globus pallidus, thalamic nuclei). We present resting state functional
      connectivity MRI (fcMRI) data from an individual who suffered a stroke leading to
      abulia. We hypothesized that, although structural imaging revealed no damage to
      the patient's ACC, fcMRI would uncover aberrant function in this region and in
      the relevant cortical networks. METHODS: Resting state correlations in the
      patient's gray matter were compared to those of age-matched controls. Using a
      novel method to identify abnormal patterns of functional connectivity in single
      subjects, we identified areas and networks with aberrant connectivity. RESULTS:
      Networks associated with memory (default mode network) and executive function
      (cingulo-opercular network) were abnormal. The patient's anterior cingulate was
      among the areas showing aberrant functional connectivity. In a rescan 3 years
      later, deficits remained stable and fcMRI findings were replicated. CONCLUSIONS:
      These findings suggest that the aberrant functional connectivity mapping approach
      described may be useful for linking stroke symptoms to disrupted network
      connectivity.

PMID- 25379446
TI  - Independent contribution of individual white matter pathways to language function
      in pediatric epilepsy patients.
AB  - BACKGROUND AND PURPOSE: Patients with epilepsy and malformations of cortical
      development (MCDs) are at high risk for language and other cognitive impairment.
      Specific impairments, however, are not well correlated with the extent and locale
      of dysplastic cortex; such findings highlight the relevance of aberrant cortico
      cortical interactions, or connectivity, to the clinical phenotype. The goal of
      this study was to determine the independent contribution of well-described white
      matter pathways to language function in a cohort of pediatric patients with
      epilepsy. MATERIALS AND METHODS: Patients were retrospectively identified from an
      existing database of pediatric epilepsy patients with the following inclusion
      criteria: 1. diagnosis of MCDs, 2. DTI performed at 3 T, and 3. language
      characterized by a pediatric neurologist. Diffusion Toolkit and Trackvis
      (http://www.trackvis.org) were used for segmentation and analysis of the
      following tracts: corpus callosum, corticospinal tracts, inferior longitudinal
      fasciculi (ILFs), inferior fronto-occipital fasciculi (IFOFs), uncinate fasciculi
      (UFs), and arcuate fasciculi (AFs). Mean diffusivity (MD) and fractional
      anisotropy (FA) were calculated for each tract. Wilcoxon rank sum test (corrected
      for multiple comparisons) was used to assess potential differences in tract
      parameters between language-impaired and language-intact patients. In a separate
      analysis, a machine learning algorithm (random forest approach) was applied to
      measure the independent contribution of the measured diffusion parameters for
      each tract to the clinical phenotype (language impairment). In other words, the
      importance of each tract parameter was measured after adjusting for the
      contribution of all other tracts. RESULTS: Thirty-three MCD patients were
      included (age range: 3-18 years). Twenty-one patients had intact language, twelve
      had language impairment. All tracts were identified bilaterally in all patients
      except for the AF, which was not identified on the right in 10 subjects and not
      identified on the left in 11 subjects. MD and/or FA within the left AF, UF, ILF,
      and IFOF differed between language-intact and language-impaired groups. However,
      only parameters related to the left uncinate, inferior fronto-occipital, and
      arcuate fasciculi were independently associated with the clinical phenotype.
      CONCLUSIONS: Scalar metrics derived from the left uncinate, inferior fronto
      occipital, and arcuate fasciculi were independently associated with language
      function. These results support the importance of these pathways in human
      language function in patients with MCDs.

PMID- 25379447
TI  - Functional neuroimaging of conversion disorder: the role of ancillary activation.
AB  - BACKGROUND: Previous functional neuroimaging studies investigating the
      neuroanatomy of conversion disorder have yielded inconsistent results that may be
      attributed to small sample sizes and disparate methodologies. The objective of
      this study was to better define the functional neuroanatomical correlates of
      conversion disorder. METHODS: Ten subjects meeting clinical criteria for
      unilateral sensory conversion disorder underwent fMRI during which a vibrotactile
      stimulus was applied to anesthetic and sensate areas. A block design was used
      with 4 s of stimulation followed by 26 s of rest, the pattern repeated 10 times.
      Event-related group averages of the BOLD response were compared between
      conditions. RESULTS: All subjects were right-handed females, with a mean age of
      41. Group analyses revealed 10 areas that had significantly greater activation (p
      < .05) when stimulation was applied to the anesthetic body part compared to the
      contralateral sensate mirror region. They included right paralimbic cortices
      (anterior cingulate cortex and insula), right temporoparietal junction (angular
      gyrus and inferior parietal lobule), bilateral dorsolateral prefrontal cortex
      (middle frontal gyri), right orbital frontal cortex (superior frontal gyrus),
      right caudate, right ventral-anterior thalamus and left angular gyrus. There was
      a trend for activation of the somatosensory cortex contralateral to the
      anesthetic region to be decreased relative to the sensate side. CONCLUSIONS:
      Sensory conversion symptoms are associated with a pattern of abnormal cerebral
      activation comprising neural networks implicated in emotional processing and
      sensory integration. Further study of the roles and potential interplay of these
      networks may provide a basis for an underlying psychobiological mechanism of
      conversion disorder.

PMID- 25379448
TI  - Brain atrophy rates in first degree relatives at risk for Alzheimer's.
AB  - A positive family history (FH) raises the risk for late-onset Alzheimer's disease
      though, other than the known risk conferred by apolipoprotein epsilon4 (ApoE4),
      much of the genetic variance remains unexplained. We examined the effect of
      family history on longitudinal regional brain atrophy rates in 184 subjects (42%
      FH+, mean age 79.9) with mild cognitive impairment (MCI) enrolled in a national
      biomarker study. An automated image analysis method was applied to T1-weighted MR
      images to measure atrophy rates for 20 cortical and subcortical regions. Mixed
      effects linear regression models incorporating repeated-measures to control for
      within-subject variation over multiple time points tested the effect of FH over a
      follow-up of up to 48 months. Most of the 20 regions showed significant atrophy
      over time. Adjusting for age and gender, subjects with a positive FH had greater
      atrophy of the amygdala (p < 0.01), entorhinal cortex (p < 0.01), hippocampus (p
      < 0.053) and cortical gray matter (p < 0.009). However, when E4 genotype was
      added as a covariate, none of the FH effects remained significant. Analyses by
      ApoE genotype showed that the effect of FH on amygdala atrophy rates was
      numerically greater in epsilon3 homozygotes than in E4 carriers, but this
      difference was not significant. FH+ subjects had numerically greater 4-year
      cognitive decline and conversion rates than FH- subjects but the difference was
      not statistically significant after adjusting for ApoE and other variables. We
      conclude that a positive family history of AD may influence cortical and temporal
      lobe atrophy in subjects with mild cognitive impairment, but it does not have a
      significant additional effect beyond the known effect of the E4 genotype.

PMID- 25379450
TI  - Atypical perception of affective prosody in Autism Spectrum Disorder.
AB  - Autism Spectrum Disorder (ASD) is characterized by impairments in language and
      social-emotional cognition. Yet, findings of emotion recognition from affective
      prosody in individuals with ASD are inconsistent. This study investigated emotion
      recognition and neural processing of affective prosody in high-functioning adults
      with ASD relative to neurotypical (NT) adults. Individuals with ASD showed mostly
      typical brain activation of the fronto-temporal and subcortical brain regions in
      response to affective prosody. Yet, the ASD group showed a trend towards
      increased activation of the right caudate during processing of affective prosody
      and rated the emotional intensity lower than NT individuals. This is likely
      associated with increased attentional task demands in this group, which might
      contribute to social-emotional impairments. 

PMID- 25379449
TI  - Intrinsic brain networks normalize with treatment in pediatric complex regional
      pain syndrome.
AB  - Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of
      chronic neuropathic pain as it either resolves spontaneously or through
      therapeutic interventions in most patients. Here we evaluated brain changes in
      well-characterized children and adolescents with P-CRPS by measuring resting
      state networks before and following a brief (median = 3 weeks) but intensive
      physical and psychological treatment program, and compared them to matched
      healthy controls. Differences in intrinsic brain networks were observed in P-CRPS
      compared to controls before treatment (disease state) with the most prominent
      differences in the fronto-parietal, salience, default mode, central executive,
      and sensorimotor networks. Following treatment, behavioral measures demonstrated
      a reduction of symptoms and improvement of physical state (pain levels and motor
      functioning). Correlation of network connectivities with spontaneous pain
      measures pre- and post-treatment indicated concomitant reductions in connectivity
      in salience, central executive, default mode and sensorimotor networks (treatment
      effects). These results suggest a rapid alteration in global brain networks with
      treatment and provide a venue to assess brain changes in CRPS pre- and post
      treatment, and to evaluate therapeutic effects.

PMID- 25379452
TI  - What affects detectability of lesion-deficit relationships in lesion studies?
AB  - Elucidating the brain basis for psychological processes and behavior is a
      fundamental aim of cognitive neuroscience. The lesion method, using voxel-based
      statistical analysis, is an important approach to this goal, identifying neural
      structures that are necessary for the support of specific mental operations, and
      complementing the strengths of functional imaging techniques. Lesion coverage in
      a population is by nature spatially heterogeneous and biased, systematically
      affecting the ability of lesion-deficit correlation methods to detect and
      localize functional associations. We have developed a simulator that allows
      investigators to model parameters in a lesion-deficit study and characterize the
      statistical bias in lesion deficit detection coverage that will result from
      specific assumptions. We used the simulator to assess the signal detection
      properties and localization accuracy of standard lesion-deficit correlation
      methods, under a simple truth model - that a critical region of interest (CR),
      when damaged, gives rise to a deficit. We considered voxel-based lesion-symptom
      mapping (VLSM) and proportional MAP-3 (PM3). Using regression analysis, we
      examined if the pattern of outcome statistics can be explained by simulation
      parameters, factors that are inherent to anatomic parcels, and lesion coverage of
      the population, which consisted of a representative sample of 351 subjects drawn
      from the Iowa Patient Registry. We examined the effect of using nonparametric
      versus parametric statistics to obtain thresholded maps and the effect of
      correcting for multiple comparisons using false discovery rate or cluster-based
      correction. Our results, which are derived from samples of realistic lesions,
      indicate that even a simple truth model yields localization errors that are
      systematic and pervasive, averaging 2 cm in the standard anatomic space, and
      tending to be directed towards areas of greater anatomic coverage. This
      displacement positions the center of mass of the detected region in a different
      anatomical region 87% of the time. This basic result is not affected by the
      choice of PM3 vs VLSM as the fundamental approach, nor is localization error
      ameliorated by incorporation of lesion size as a covariate in the VLSM approach,
      or by data distribution-driven approaches to controlling multiple spatial
      comparisons (false discovery rate or cluster-based correction approaches). Our
      simulations offer a quantitative basis for interpreting lesion studies in
      cognitive neuroscience. We suggest ways in which lesion simulation and analysis
      frameworks could be productively extended.

PMID- 25379451
TI  - White matter correlates of sensory processing in autism spectrum disorders.
AB  - Autism spectrum disorder (ASD) has been characterized by atypical socio
      communicative behavior, sensorimotor impairment and abnormal neurodevelopmental
      trajectories. DTI has been used to determine the presence and nature of
      abnormality in white matter integrity that may contribute to the behavioral
      phenomena that characterize ASD. Although atypical patterns of sensory responding
      in ASD are well documented in the behavioral literature, much less is known about
      the neural networks associated with aberrant sensory processing. To address the
      roles of basic sensory, sensory association and early attentional processes in
      sensory responsiveness in ASD, our investigation focused on five white matter
      fiber tracts known to be involved in these various stages of sensory processing:
      superior corona radiata, centrum semiovale, inferior longitudinal fasciculus,
      posterior limb of the internal capsule, and splenium. We acquired high angular
      resolution diffusion images from 32 children with ASD and 26 typically developing
      children between the ages of 5 and 8. We also administered sensory assessments to
      examine brain-behavior relationships between white matter integrity and sensory
      variables. Our findings suggest a modulatory role of the inferior longitudinal
      fasciculus and splenium in atypical sensorimotor and early attention processes in
      ASD. Increased tactile defensiveness was found to be related to reduced
      fractional anisotropy in the inferior longitudinal fasciculus, which may reflect
      an aberrant connection between limbic structures in the temporal lobe and the
      inferior parietal cortex. Our findings also corroborate the modulatory role of
      the splenium in attentional orienting, but suggest the possibility of a more
      diffuse or separable network for social orienting in ASD. Future investigation
      should consider the use of whole brain analyses for a more robust assessment of
      white matter microstructure.

PMID- 25379454
TI  - 48 echo T2 myelin imaging of white matter in first-episode schizophrenia:
      evidence for aberrant myelination.
AB  - Myelin water imaging provides a novel strategy to assess myelin integrity and
      corresponding clinical relationships in psychosis, of particular relevance in
      frontal white matter regions. In the current study, T2 myelin water imaging was
      used to assess the myelin water fraction (MWF) signal from frontal areas in a
      sample of 58 individuals experiencing first-episode psychosis (FEP) and 44
      healthy volunteers. No differences in frontal MWF were observed between FEP
      subjects and healthy volunteers; however, differences in normal patterns of
      associations between frontal MWF and age, education and IQ were seen. Significant
      positive relationships between frontal MWF and age, North American Adult Reading
      Test (NAART) IQ, and years of completed education were observed in healthy
      volunteers. In contrast, only the relationship between frontal MWF and NAART IQ
      was significant after Bonferroni correction in the FEP group. Additionally,
      significant positive relationships between age and MWF in the anterior and
      posterior internal capsules, the genu, and the splenium were observed in healthy
      volunteers. In FEP subjects, only the relationship between age and MWF in the
      splenium was statistically significant. Frontal MWF was not associated with local
      white matter volume. Altered patterns of association between age, years of
      education, and MWF in FEP suggest that subtle disturbances in myelination may be
      present early in the course of psychosis.

PMID- 25379453
TI  - GABA and glutamate in schizophrenia: a 7 T 1H-MRS study.
AB  - Schizophrenia is characterized by loss of brain volume, which may represent an
      ongoing pathophysiological process. This loss of brain volume may be explained by
      reduced neuropil rather than neuronal loss, suggesting abnormal synaptic
      plasticity and cortical microcircuitry. A possible mechanism is hypofunction of
      the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory
      GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal
      neurons. Disinhibition of pyramidal cells may result in excessive stimulation by
      glutamate, which in turn could cause neuronal damage or death through
      excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine
      and choline concentrations in the prefrontal and parieto-occipital cortices were
      measured in 17 patients with schizophrenia and 23 healthy controls using proton
      magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T.
      Significantly lower GABA/Cr ratios were found in patients with schizophrenia in
      the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios
      inversely correlated with cognitive functioning in the patients. No significant
      change in the GABA/Cr ratio was found between patients and controls in the
      parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and
      choline differed in patients and controls in the prefrontal and parieto-occipital
      cortices. Our findings support a mechanism involving altered GABA levels
      distinguished from glutamate levels in the medial prefrontal cortex in
      schizophrenia, particularly in high functioning patients. A (compensatory) role
      for GABA through altered inhibitory neurotransmission in the prefrontal cortex
      may be ongoing in (higher functioning) patients with schizophrenia.

PMID- 25379455
TI  - Cortical plasticity in episodic and chronic cluster headache.
AB  - Cluster headache (CH) is characterized by recurrent episodes of excruciatingly
      painful, unilateral headache attacks typically accompanied by trigeminal
      autonomic symptoms. Due to its rhythm with alternating episodes of pain and no
      pain, it is an excellent model to investigate whether structural brain changes
      detected by magnetic resonance based voxel-based-morphometry (VBM) reflect the
      cause of the disease, may be a consequence of the underlying disease other than
      pain, or may simply be caused by the sensation of pain itself. We investigated 91
      patients with CH in different stages of their disease using VBM and compared them
      to 78 age- and gender-matched healthy controls. We detected distinct regional
      gray matter (GM) changes in different brain regions including the temporal lobe,
      the hippocampus, the insular cortex and the cerebellum. The extent, location and
      direction of observed GM alterations depended on the state of disease and
      appeared dynamic in relation to pain state (i.e., pain vs. no-pain). No
      hypothalamic changes were detected in CH patients compared to healthy controls.
      The GM changes observed in this study are highly dynamic and thereby reflect the
      cortical plasticity of the brain in regard to pain. This observed dynamic may
      provide an explanation of the diverse results of previous VBM studies in pain.
      Regarding CH the results suggest that the disease is more likely to be caused by
      a network dysfunction rather than by a single malfunctioning structure. 

PMID- 25379457
TI  - Brain volume estimation from post-mortem newborn and fetal MRI.
AB  - OBJECTIVE: Minimally invasive autopsy using post-mortem magnetic resonance
      imaging (MRI) is a valid alternative to conventional autopsy in fetuses and
      infants. Estimation of brain weight is an integral part of autopsy, but manual
      segmentation of organ volumes on MRI is labor intensive and prone to errors,
      therefore unsuitable for routine clinical practice. In this paper we aim to show
      that volumetric measurements of the post-mortem fetal and neonatal brain can be
      accurately estimated using semi-automatic techniques and a high correlation can
      be found with the weights measured from conventional autopsy results. METHODS:
      The brains of 17 newborn subjects, part of Magnetic Resonance Imaging Autopsy
      Study (MaRIAS), were segmented from post-mortem MR images into cerebrum,
      cerebellum and brainstem using a publicly available neonate brain atlas and semi
      automatic segmentation algorithm. The results of the segmentation were averaged
      to create a new atlas, which was then used for the automated atlas-based
      segmentation of 17 MaRIAS fetus subjects. As validation, we manually segmented
      the MR images from 8 subjects of each cohort and compared them with the automatic
      ones. The semi-automatic estimation of cerebrum weight was compared with the
      results of the conventional autopsy. RESULTS: The Dice overlaps between the
      manual and automatic segmentations are 0.991 and 0.992 for cerebrum, 0.873 and
      0.888 for cerebellum and 0.819 and 0.815 for brainstem, for newborns and fetuses,
      respectively. Excellent agreement was obtained between the estimated MR weights
      and autopsy gold standard ones: mean absolute difference of 5 g and 2% maximum
      error for the fetus cohort and mean absolute difference of 20 g and 11% maximum
      error for the newborn one. CONCLUSIONS: The high correlation between the obtained
      segmentation and autopsy weights strengthens the idea of using post-mortem MRI as
      an alternative for conventional autopsy of the brain.

PMID- 25379456
TI  - Cortical substrates and functional correlates of auditory deviance processing
      deficits in schizophrenia.
AB  - Although sensory processing abnormalities contribute to widespread cognitive and
      psychosocial impairments in schizophrenia (SZ) patients, scalp-channel measures
      of averaged event-related potentials (ERPs) mix contributions from distinct
      cortical source-area generators, diluting the functional relevance of channel
      based ERP measures. SZ patients (n = 42) and non-psychiatric comparison subjects
      (n = 47) participated in a passive auditory duration oddball paradigm, eliciting
      a triphasic (Deviant-Standard) tone ERP difference complex, here termed the
      auditory deviance response (ADR), comprised of a mid-frontal mismatch negativity
      (MMN), P3a positivity, and re-orienting negativity (RON) peak sequence. To
      identify its cortical sources and to assess possible relationships between their
      response contributions and clinical SZ measures, we applied independent component
      analysis to the continuous 68-channel EEG data and clustered the resulting
      independent components (ICs) across subjects on spectral, ERP, and topographic
      similarities. Six IC clusters centered in right superior temporal, right inferior
      frontal, ventral mid-cingulate, anterior cingulate, medial orbitofrontal, and
      dorsal mid-cingulate cortex each made triphasic response contributions. Although
      correlations between measures of SZ clinical, cognitive, and psychosocial
      functioning and standard (Fz) scalp-channel ADR peak measures were weak or
      absent, for at least four IC clusters one or more significant correlations
      emerged. In particular, differences in MMN peak amplitude in the right superior
      temporal IC cluster accounted for 48% of the variance in SZ-subject performance
      on tasks necessary for real-world functioning and medial orbitofrontal cluster
      P3a amplitude accounted for 40%/54% of SZ-subject variance in positive/negative
      symptoms. Thus, source-resolved auditory deviance response measures including MMN
      may be highly sensitive to SZ clinical, cognitive, and functional
      characteristics.

PMID- 25379458
TI  - Dietary feeding of Flavokawain A, a Kava chalcone, exhibits a satisfactory safety
      profile and its association with enhancement of phase II enzymes in mice.
AB  - Flavokawain A (FKA), a major chalcone in the Kava plant, has recently
      demonstrated promising anti-cancer activities. A systematic evaluation of FKA's
      safety profile has not been reported before. In this study, male FVB/N mice were
      fed with an AIN-76A diet or AIN-76A diet supplemented with 0.6% (6 g/kg food) FKA
      or 0.6% commercial kava root extract (KRE) for three weeks. Dietary feeding of
      FKA did not affect food consumption and body weight. Histopathological
      examination of liver, kidney, colon, lung, heart, spleen, and thymus revealed no
      signs of FKA-induced toxicity. Biochemical serum analysis and histological
      examination confirmed normal organ function in FKA-treated mice. The cytotoxicity
      profile showed FKA had minimal side effects on bone marrow and small intestinal
      epithelial cells compared with Adriamycin. In addition, oral feeding of FKA
      increased activities of both glutathione S-transferase and quinone reductase in
      the liver, lung, prostate and bladder tissues of mice. In comparison, dietary
      feeding of 0.6% KRE increased liver/body weight ratio and decreased spleen,
      thymus, and testis/body weight ratios, as well as induced nodular proliferation
      in liver tissues. Therefore, dietary feeding FKA showed no adverse effects on
      major organ function and homeostasis in mice, suggesting the potential of FKA for
      chemoprevention study of human cancers.

PMID- 25379459
TI  - French pre-hospital trauma triage criteria: Does the "pre-hospital resuscitation"
      criterion provide additional benefit in triage?
AB  - AIM: To evaluate the performance of the specific French Vittel "Pre-Hospital (PH)
      resuscitation" criteria in selecting polytrauma patients during the pre-hospital
      stage and its potential to increase the positive predictive value (PPV) of pre
      hospital trauma triage. METHODS: This was a monocentric prospective cohort study
      of injured adults transported by emergency medical service to a trauma center.
      Patients who met any of the field trauma triage criteria were considered "triage
      positive". Hospital data was statistically linked to pre-hospital records. The
      primary outcome of defining a "major trauma patient" was Injury Severity Score
      (ISS) > 16. RESULTS: There were a total of 200 injured patients evaluated over a
      2 years period who met at least 1 triage criterion. The number of false positives
      was 64 patients (ISS < 16). The PPV was 68%. The sensitivity and the negative
      predictive value could not be evaluated in this study since it only included
      patients with positive Vittel criteria. The criterion of "PH resuscitation" was
      present for 64 patients (32%), but 10 of them had an ISS < 16. This was
      statistically significant in correlation with the severity of the trauma in
      univariate analysis (OR = 7.2; P = 0.005; 95%CI: 1.6-31.6). However, despite this
      correlation the overall PPV was not significantly increased by the use of the
      criterion "PH resuscitation" (68% vs 67.8%). CONCLUSION: The criterion of "pre
      hospital resuscitation" was statistically significant with the severity of the
      trauma, but did not increase the PPV. The use of "pre-hospital resuscitation"
      criterion could be re-considered if these results are confirmed by larger
      studies.

PMID- 25379460
TI  - Steroid hormone synthetic pathways in prostate cancer.
AB  - While androgen deprivation therapy (ADT) remains the primary treatment for
      metastatic prostate cancer (PCa) since the seminal recognition of the disease as
      androgen-dependent by Huggins and Hodges in 1941, therapy is uniformly marked by
      progression to castration-resistant prostate cancer (CRPC) over a period of about
      18 months, with an ensuing median survival of 1 to 2 years. Importantly,
      castration does not eliminate androgens from the prostate tumor microenvironment.
      Castration resistant tumors are characterized by elevated tumor androgens that
      are well within the range capable of activating the AR and AR-mediated gene
      expression, and by steroid enzyme alterations which may potentiate de novo
      androgen synthesis or utilization of circulating adrenal androgens. The
      dependence of CRPC on intratumoral androgen metabolism has been modeled in vitro
      and in vivo, and residual intratumoral androgens are implicated in nearly every
      mechanism by which AR-mediated signaling promotes castration-resistant disease.
      These observations suggest that tissue based alterations in steroid metabolism
      contribute to the development of CRPC and underscore these metabolic pathways as
      critical targets of therapy. Herein, we review the accumulated body of evidence
      which strongly supports intracrine (tumoral) androgen synthesis as an important
      mechanism underlying PCa progression. We first discuss the presence and
      significance of residual prostate tumor androgens in the progression of CRPC. We
      review the classical and non-classical pathways of androgen metabolism, and how
      dysregulated expression of these enzymes is likely to potentiate tumor androgen
      production in the progression to CRPC. Next we review the in vitro and in vivo
      data in human tumors, xenografts, and cell line models which demonstrate the
      capacity of prostate tumors to utilize cholesterol and adrenal androgens in the
      production of testosterone (T) and dihydrotestosterone (DHT), and briefly review
      the potential role of exogenous influences on this process. Finally, we discuss
      the emerging data regarding mechanisms of response and resistance to potent
      ligand synthesis inhibitors entering clinical practice, and conclude by
      discussing the implications of these findings for future therapy.

PMID- 25379462
TI  - Acupuncture ( zhen jiu) - an emerging adjunct in routine oral care.
AB  - Acupuncture ( Zhen Jiu) ('acus' (needle) + 'punctura' (to puncture)) is the
      stimulation of specific points along the skin of the body involving various
      methods such as penetration by thin needles or the application of heat, pressure,
      or laser light. Acupuncture ( Zhen Jiu) aims to treat a range of medical and
      dental ailments, though is most commonly used for pain relief. This article
      reviews about the various possible roles of acupuncture ( Zhen Jiu) in clinical
      dental practice. Acupuncture ( Zhen Jiu) has potential in supplementing
      conventional treatment procedures by its diverse applicability outreach. Role of
      acupuncture ( Zhen Jiu) in dental practice has been well supported by clinical
      trials. Its role in alleviating facial pain, pre-operative and post-operative
      dental pain has led to its widespread application. Its role as sole analgesic for
      treatment procedure has to be tested. It's It is a thought that acupuncture (
      Zhen Jiu) may prove an indispensible supplement to conventional treatment
      modalities and more of clinical trials and studies are required to prove the
      efficacy. Acupuncture ( Zhen Jiu) is not a miracle cure and is not going to
      replace the drill. However, the technique can be a supplement to conventional
      treatments in TMDs, facial pain, pain management Sjoegrens syndrome, and in
      phobias and anxiety. The application and use of Acupuncture ( Zhen Jiu) comes
      with some side effects. Proper training needs to be obtained before commencement
      of any procedure related to acupuncture ( Zhen Jiu). Various training programs
      are offered to train clinical practitioners the apt method to use acupuncture (
      Zhen Jiu). 

PMID- 25379463
TI  - Revisiting Terminalia arjuna - An Ancient Cardiovascular Drug.
AB  - Terminalia arjuna, commonly known as arjuna, belongs to the family of
      Combretaceae. Its bark decoction is being used in the Indian subcontinent for
      anginal pain, hypertension, congestive heart failure, and dyslipidemia, based on
      the observations of ancient physicians for centuries. The utility of arjuna in
      various cardiovascular diseases needs to be studied further. Therefore, the
      present review is an effort to give a detailed survey of the literature
      summarizing the experimental and clinical studies pertinent to arjuna in
      cardiovascular disorders, which were particularly performed during the last
      decade. Systematic reviews, meta-analyses, and clinical studies of arjuna were
      retrieved through the use of PubMed, Google Scholar, and Cochrane databases. Most
      of the studies, both experimental and clinical, have suggested that the crude
      drug possesses anti-ischemic, antioxidant, hypolipidemic, and antiatherogenic
      activities. Its useful phytoconstituents are: Triterpenoids, beta-sitosterol,
      flavonoids, and glycosides. Triterpenoids and flavonoids are considered to be
      responsible for its beneficial antioxidant cardiovascular properties. The drug
      has shown promising effect on ischemic cardiomyopathy. So far, no serious side
      effects have been reported with arjuna therapy. However, its long-term safety
      still remains to be elucidated. Though it has been found quite useful in angina
      pectoris, mild hypertension, and dyslipidemia, its exact role in
      primary/secondary coronary prevention is yet to be explored. 

PMID- 25379461
TI  - Dietary agents and phytochemicals in the prevention and treatment of experimental
      ulcerative colitis.
AB  - Inflammatory bowel diseases (IBDs), consisting mainly of ulcerative colitis (UC)
      and Crohn's disease (CD), are important immune-mediated diseases of the
      gastrointestinal tract. The etiology of the disease includes environmental and
      genetic factors. Its management presents a constant challenge for
      gastroenterologists and conventional surgeon. 5-Amninosalicylates, antibiotics,
      steroids, and immune modulators have been used to reduce the symptoms and for
      maintenance of remission. Unfortunately, long-term usage of these agents has been
      found to lead to severe toxicities, which are deterrent to the users. Pre
      clinical studies carried out in the recent past have shown that certain dietary
      agents, spices, oils, and dietary phytochemicals that are consumed regularly
      possess beneficial effects in preventing/ameliorating UC. For the first time,
      this review addresses the use of these dietary agents and spices in the treatment
      and prevention of IBD and also emphasizes on the mechanisms responsible for their
      effects. 

PMID- 25379464
TI  - Pomegranate from Oman Alleviates the Brain Oxidative Damage in Transgenic Mouse
      Model of Alzheimer's disease.
AB  - Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology.
      Pomegranates ( Shi Liu) contain very high levels of antioxidant polyphenolic
      substances, as compared to other fruits and vegetables. Polyphenols have been
      shown to be neuroprotective in different model systems. Here, the effects of the
      antioxidant-rich pomegranate fruit grown in Oman on brain oxidative stress status
      were tested in the AD transgenic mouse. The 4-month-old mice with double Swedish
      APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA. Four-month
      old Tg2576 mice were fed with 4% pomegranate or control diet for 15 months and
      then assessed for the influence of diet on oxidative stress. Significant increase
      in oxidative stress was found in terms of enhanced levels of lipid peroxidation
      (LPO) and protein carbonyls. Concomitantly, decrease in the activities of
      antioxidant enzymes was observed in Tg2576 mice treated with control diet.
      Supplementation with 4% pomegranate attenuated oxidative damage, as evidenced by
      decreased LPO and protein carbonyl levels and restoration in the activities of
      the antioxidant enzymes [superoxide dismutase (SOD), catalase, glutathione
      peroxidase (GPx), glutathione (GSH), and Glutathione S transferase (GST)]. The
      activities of membrane-bound enzymes [Na(+) K(+)-ATPase and acetylcholinesterase
      (AChE)] were altered in the brain regions of Tg2576 mouse treated with control
      diet, and 4% pomegranate supplementation was able to restore the activities of
      enzymes to comparable values observed in controls. The results suggest that the
      therapeutic potential of 4% pomegranate in the treatment of AD might be
      associated with counteracting the oxidative stress by the presence of active
      phytochemicals in it. 

PMID- 25379465
TI  - Induction of Angiogenesis in Zebrafish Embryos and Proliferation of Endothelial
      Cells by an Active Fraction Isolated from the Root of Astragalus membranaceus
      using Bioassay-guided Fractionation.
AB  - The objective of the study was to identify the active fraction(s) from AR aqueous
      extract responsible for promoting angiogenesis using bioassay-guided
      fractionation. The angiogenic activity was screened by monitoring the increase of
      sprout number in sub-intestinal vessel (SIV) of the transgenic zebrafish embryos
      after they were treated with 0.06-0.25 mg/ml of AR aqueous extract or its
      fraction(s) for 96 h. Furthermore, the angiogenic effect was evaluated in treated
      zebrafish embryos by measuring the gene expression of angiogenic markers (VEGFA,
      KDR, and Flt-1) using real-time polymerase chain reaction (RT-PCR), and in human
      microvascular endothelial cell (HMEC-1) by measuring cell proliferation using 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, (3)H
      thymidine uptake assay, and cell cycle analysis. A major active fraction (P1-1
      1), which was identified as glycoproteins, was found to significantly stimulate
      sprout formation (2.03 +/- 0.27) at 0.125 mg/ml (P < 0.001) and up-regulate the
      gene expression of VEGFA, KDR, and Flt-1 by 2.6-fold to 8.2-fold. Additionally,
      0.031-0.125 mg/ml of P1-1-1 was demonstrated to significantly stimulate cell
      proliferation by increasing cell viability (from 180% to 205%), (3)H-thymidine
      incorporation (from 126% to 133%) during DNA synthesis, and the shift of cell
      population to S phase of cell cycle. A major AR active fraction consisting of
      glycoproteins was identified, and shown to promote angiogenesis in zebrafish
      embryos and proliferation of endothelial cells in vitro. 

PMID- 25379466
TI  - Wound-healing Activity of the Aqueous Leaf Extract and Fractions of Ficus
      exasperata (Moraceae) and its Safety Evaluation on Albino Rats.
AB  - Ficus exasperata have been reported to have wide applications in the treatment of
      many human diseases. However, its traditional use in the treatment of wounds has
      not been validated by any scientific study. Also, its safety in the management of
      chronic disease conditions requires attention. We evaluated the wound-healing
      activity of the aqueous extract and fractions of F. exasperata, as well as its
      safety after subchronic oral administration. Similar percentage of wound
      contraction was observed with 5% w/w extract ointment application and
      administration of cicatrin powder (standard) on the 4(th) day, while better
      contraction than the standard was recorded with higher concentrations of the
      extract ointment. Of all the fractions tested, significant (P < 0.05) contraction
      was only noticed in chloroform fraction, though lower than that of the aqueous
      extract. The extract also showed concentration-dependent inhibition of all the
      tested microbial isolates. Extract administered up to 5000 mg/kg (single dose
      administration) did not cause any mortality after 24 h. Mortality was, however,
      recorded at 4000 mg/kg within the first 20 days of subchronic administration of
      the extract. Significant (P < 0.05) increases in alanine aminotransaminase (ALT),
      aspartate aminotransaminase (AST), and in particular, alkaline phosphatase (ALP)
      were observed at different doses and time periods. Pathological and histological
      changes were noticed in the liver and kidney on the 91(st) day of the study with
      4000 mg/kg of the extract. Except for the significant (P < 0.05) reduction in WBC
      on the 91(st) day, no other significant (P < 0.05) changes were observed in other
      hematological parameters. The aqueous extract demonstrated better wound-healing
      activity than its fractions; however, the extract may not be safe at higher doses
      for subchronic oral administration, as may be the case in the management of
      chronic disease conditions. 

PMID- 25379467
TI  - Evaluation of Anticancer, Antioxidant, and Possible Anti-inflammatory Properties
      of Selected Medicinal Plants Used in Indian Traditional Medication.
AB  - The present study was carried out to evaluate the anticancer, antioxidant, and
      possible anti-inflammatory properties of diverse medicinal plants frequently used
      in Indian traditional medication. The selected botanicals such as Soymida
      fembrifuga (Roxb.) A. Juss. (Miliaceae), Tinospora cordifolia (Willd.) Miers.
      (Menispermaceae), Lavandula bipinnata (L.) O. Ktze. (Lamiaceae), and Helicteres
      isora L. (Sterculiaceae) extracted in different solvents were evaluated for their
      in vitro anticancer and antioxidant activities. The results obtained indicate
      that H. isora has potent cytotoxic activity toward the selected cancer cells such
      as HeLa-B75 (34.21 +/- 0.24%), HL-60 (30.25 +/- 1.36%), HEP-3B (25.36 +/- 1.78%),
      and PN-15 (29.21 +/- 0.52%). Interestingly, the selected botanicals selectively
      inhibited cyclooxygenase-2 (COX-2) more than (COX-1), which are the key enzymes
      implicated in inflammation. COX-2 inhibition was observed to be in the range of
      19.66-49.52% as compared to COX-1 inhibition (3.93-19.61%). The results of the
      antioxidant study revealed that the selected plants were found to be effective
      1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and superoxide radical (SOR)
      scavenging agents. High-performance thin layer chromatography (HPTLC) fingerprint
      of flavonoids was used as a measure of quality control of the selected plant
      samples. The results of the present findings strengthen the potential of the
      selected plants as a resource for the discovery of novel anticancer, anti
      inflammatory, and antioxidant agents. 

PMID- 25379468
TI  - Antimicrobial Potential of Helicanthus elastica (Desr.) Danser - A less explored
      Indian mistletoe Growing on Mango Trees.
AB  - Helicanthus elastica (Desr.) Danser (Loranthaceae) is a less-known medicinally
      important mistletoe species occurring in India. It is used to check abortion, and
      also in vesical calculi and kidney affections. There are no detailed studies
      reporting the antimicrobial potential of this plant. Based on the traditional use
      and the rich phenolic composition of the whole plant, the antimicrobial property
      of the alcohol extract was analyzed and the results are outlined in the present
      paper. For the analysis, zone of inhibition, and minimum inhibitory concentration
      were used, and the total activity was assayed by standard methodologies. The
      antimicrobial activity was studied against bacteria like Aeromonas hydrophila,
      Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, methicillin-resistant
      Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, Vibrio
      fischeri, and a fungus Candida albicans. Of the eight tested bacteria, the
      alcoholic extract of H. elastica was found to be active against K. pneumoniae, A.
      hydrophila, E. coli, and V. fischeri at concentration ranging from 250 to 500
      MUg/ml. C. albicans showed inhibition only at a concentration of 2000 MUg/ml. 

PMID- 25379469
TI  - Comparative Evaluation of the Complementary and Alternative Medicine Therapy and
      Conventional Therapy Use for Musculoskeletal Disorders Management and Its
      Association with Job Satisfaction among Dentists of West India.
AB  - Musculoskeletal problems have become a significant issue in the profession of
      dentistry. There are currently no recommended effective disease-preventing and
      modifying remedies. High prevalence rates for musculoskeletal disorders (MSDs)
      among dentists have been reported in the literature. Complementary and
      alternative medicine can be helpful in managing and preventing the MSDs. The
      purpose of this study was to determine if dentists in the western part of India
      are using complementary and alternative medicine therapies for MSDs, and also to
      find if those who use complementary and alternative medicine therapies have
      greater job/career satisfaction compared to conventional therapy (CT) users.
      Dentists of western India registered under the Dental Council of India (N = 2166)
      were recruited for the study. Data were analyzed using univariate and bivariate
      analyses and logistic regression. A response rate of 73% (n = 1581) was obtained,
      of which 79% (n = 1249) was suffering from MSDs. The use of complementary and
      alternative medicine or CT was reported by 90% (n = 1124) of dentists with MSDs.
      Dentists using complementary and alternative medicine reported greater health (P
      < 0.001) and carrier satisfaction (P < 0.001) and were able to work as many hours
      they wanted (P < 0.001) compared to CT users. Complementary and alternative
      medicine therapies may improve the quality of life and enhance job satisfaction
      for a dentist who suffers from MSDs. 

PMID- 25379470
TI  - Sedative-hypnotic Effect of Ash of Silver in Mice: A Reverse Pharmacological
      Study.
AB  - Ash of silver is used in traditional systems of medicine for various neurological
      conditions like insomnias, neuralgias, anxiety disorders, and convulsions. The
      present study was conducted to evaluate the sedative-hypnotic activity of ash of
      silver in comparison to pentobarbitone (standard drug) in albino mice. The mice
      were divided into four groups as follows: Group 1 (control): Gum acacia [GA; 1%
      per os (p.o.)], group 2 (standard): Pentobarbitone [50 mg/kg intraperitoneal
      (i.p.)], group 3 (test): Ash of silver (50 mg/kg p.o.), and group 4: Ash of
      silver (50 mg/kg p.o.) given 30 min prior to administration of pentobarbitone (50
      mg/kg i.p.). Time of onset, recovery, and total duration of loss of righting
      reflex were studied. Ash of silver (test) produced significant sedation (P <
      0.01) compared to control (GA 1%), but the effect was significantly less compared
      to that of standard pentobarbitone at the doses used. Also, significant
      potentiation (P < 0.001) of the sedative-hypnotic effect of pentobarbitone was
      observed with the test drug. 

PMID- 25379471
TI  - Effect of two herbal mouthwashes on gingival health of school children.
AB  - This study aimed at determining the effect of indigenously prepared neem and
      mango chewing stick mouthwashes on plaque and gingival indices. A sample of 105
      children aged 12-15 years was randomized into three groups, namely neem, mango,
      and chlorhexidine mouthwash groups. All the children were examined at baseline
      and gingival and plaque indices were recorded. Baseline scores for plaque and
      gingivitis were fair and moderate, respectively, in all the three groups and
      there existed no statistically significant difference among them. Ten millilitres
      each of herbal and chlorhexidine mouthwashes (0.2%) were administered according
      to the group allocation twice daily for 21 days. Indices were reassessed at 21
      days (immediately after intervention) and at 1 month, 2 months, and 3 months
      after discontinuing the mouthwashes. Statistically significant reduction (P <
      0.001) in plaque index was found in all the three mouthwash groups at 21 days and
      at 1 month from discontinuing the mouthwash. Chlorhexidine additionally showed
      statistically significant reduction in plaque index at 2 months from
      discontinuing the mouthwash. Statistically significant reduction (P < 0.001) in
      gingival index was found in all the three mouthwash groups at 21 days
      (immediately after discontinuing the mouthwash) and at 1 and 2 months from
      discontinuing the mouthwash. To conclude, all the three mouthwashes were
      effective antiplaque and antigingivitis agents. Chlorhexidine and neem possess
      equivalent efficacy in reducing plaque, while chlorhexidine has superior
      antigingivitis properties. 

PMID- 25379472
TI  - Anticancer Studies of Aqueous Extract of Roots and Leaves of Pandanus
      Odoratissimus f. ferreus (Y. Kimura) Hatus: An In Vitro Approach.
AB  - A number of medicinal plant extracts are being used against various diseases in
      different systems of medicine such as Ayurveda, Unani, and Siddha, but only a few
      of them have been scientifically explored. The objective of the present study was
      to explore the dose-dependent in vitro anticancer effects of the extracts of
      Pandanus odoratissimus whose scientific documentation as an anticancer agent is
      lacking despite being used traditionally. The dried parts of roots and leaves
      were extracted with methanol (MEPO) and water (AEPO). The extracts were then
      subjected to in vitro cytotoxic and antimitotic screening by brine shrimp
      lethality assay and onion root tip method, respectively. Further, the behavior of
      the extracts on calu-6 (non-small cell lung cancer cell lines), PBMC (peripheral
      blood mononuclear cells) and WI (lung fibroblast cell lines) was studied using 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay followed by flow
      cytometric analysis on calu-6 cell lines. AEPO showed significant cytotoxic and
      antimitotic activities. It showed 100% lethality of brine shrimps at 80 MUg/ml
      and an LC50 of 33.33 MUg/ml, which was eightfold higher than that of synthetic
      standard podophyllotoxin (4.16 MUg/ml). AEPO at 10 mg/ml concentration showed
      significant antimitotic activity by showing 3% mitotic index. which was more than
      that of standard cyclophosphamide with 4% mitotic index in comparison to control.
      There was a significant reduction in cell proliferation of calu-6 cells, ranging
      from 56 to 35%, after 24-48 h of treatment with 200 MUg/ml (P < 0.001) of AEPO,
      while AEPO remained unaffected on PBMC and WI-38 cel lines. Cell cycle analysis
      revealed that AEPO at 50 MUg/ml and 100 MUg/ml significantly increased the number
      of cells in sub G0-G1 phase, indicating the cells entering in to apoptotic phase.
      These results suggest that aqueous extract of P. odoratissimus possesses better
      anticancer activity. The plant has the potential to be used in anticancer
      therapy, and this study scientifically validated the folklore use of this plant. 

PMID- 25379473
TI  - Total Phenol Content and In Vitro Antioxidant Potential of Helicanthus elastica
      (Desr.) Danser-A Less-explored Indian Mango Mistletoe.
AB  - Natural products are an important source of antioxidant molecules like tannins,
      phenolic compounds, flavonoids, etc., Helicanthus elastica (Desr.) Danser
      (Loranthaceae) is one such plant belonging to the category of mistletoe, and
      grows commonly on the mango trees in India. In the present study, an attempt has
      been made to assess the antioxidant properties of the plant. Ethanol extract of
      H. elastica growing on mango tree was studied using different in vitro models.
      Shade-dried whole plant material was extracted with ethanol by cold percolation.
      Fifty milligrams of the alcohol extract of H. elastica was weighed and dissolved
      in 10 ml of methanol. The resultant 5 mg/ml solution was suitably diluted to
      obtain different concentrations. Total phenol content, reducing power assay, and
      scavenging of free radicals like nitric oxide, hydroxyl, hydrogen peroxide, and
      1,1-diphenyl-2-picrylhydrazyl were studied by standardized in vitro chemical
      methods using ascorbic acid as the standard. The total phenol content of the
      plant was found to be 1.89% w/w. The extract showed good reducing power as well
      as scavenging of free radicals (nitric oxide, hydroxyl, superoxide anion, and
      hydrogen peroxide) at concentrations ranging from 5 to 100 MUg/ml. The study
      revealed the antioxidant potential of H. elastica. 

PMID- 25379474
TI  - A validation study of homeopathic prescribing and patient care indicators.
AB  - A preliminary version of the homeopathic prescribing and patient care indicators
      was available. The instrument was modified further in this study with an
      intention to address formally its validity and reliability, audit prescriptions,
      identify areas of sub-optimal prescribing, and highlight target areas for
      improving the quality of practices. A cross-sectional study with record analysis
      was conducted on systematically sampled 377 patients of Mahesh Bhattacharyya
      Homeopathic Medical College and Hospital (MBHMC and H), Howrah, West Bengal,
      India. The outcome measures were homeopathic prescribing indicators (6 items) and
      patient care indicators (5 items). Individualized homeopathic prescriptions
      predominated in the encounters. Areas demanding immediate attention were
      extremely poor labeling of drugs dispensed from the hospital pharmacy, improper
      record of case history and disease diagnosis, ongoing therapies, and
      investigational findings in the prescriptions. Internal consistency of the
      overall instrument was estimated to be good (Cronbach's alpha: Prescribing
      indicators 0.752 and patient care indicators 0.791). The prescribing indicators,
      except items 1 and 3, reflected acceptable item-corrected total correlations -
      Pearson's r from 0.58 (95% CI: 0.52-0.65) to 0.74 (95% CI: 0.69-0.78). The
      patient care indicators, except item 2, showed acceptable correlations -
      Pearson's r from 0.40 (95% CI: 0.31-0.48) to 0.82 (95% CI: 0.78-0.85). The
      instrument also showed high discriminant validity (prescribing indicators P <
      0.0001 and patient care indicators P < 0.0001). Improper prescribing practice was
      quite rampant and corrective measures are warranted. The developed indicators
      appeared to be validated and reliable; however, they are amendable for further
      development. 

PMID- 25379475
TI  - Effects of goshajinkigan, hachimijiogan, and rokumigan on mechanical allodynia
      induced by Paclitaxel in mice.
AB  - Peripheral neuropathy is a major dose-limiting side effect of the
      chemotherapeutic agent paclitaxel. This study examined whether the three related
      traditional herbal formulations, goshajinkigan (GJG; Niu Che Shen Qi Wan),
      hachimijiogan (HJG; Ba Wei Di Huang Wan), and rokumigan (RMG; Liu Wei Wan), would
      relieve paclitaxel-induced mechanical allodynia in mice. A single intraperitoneal
      injection of paclitaxel (5 mg/kg) induced mechanical allodynia, which peaked on
      day 14 after injection. On day 14 after paclitaxel injection, oral administration
      of GJG (0.1-1.0 g/kg) produced a significant inhibition of established allodynia,
      but HJG and RMG did not affect the allodynia. Repeated oral administration of GJG
      (0.1-1.0 g/kg) starting from the day after paclitaxel injection did not affect
      allodynia development, but significantly inhibited allodynia exacerbation.
      Repeated oral administration of HJG produced a slight inhibition of allodynia
      exacerbation, but that of RMG did not. These results suggest that prophylactic
      administration of GJG is effective in preventing the exacerbation of paclitaxel
      induced allodynia. The herbal medicines Plantaginis Semen ( Che Qian Zi) and
      Achyranthis Radix ( Niu Xi), which are present in GJG but not in HJG, may
      contribute to the inhibitory action of GJG on the exacerbation of paclitaxel
      induced allodynia. 

PMID- 25379476
TI  - The antinociceptive effects of tualang honey in male sprague-dawley rats: a
      preliminary study.
AB  - Tualang honey ( Feng Mi) is known to have anti-inflammatory property, but its
      antinociceptive property has not been extensively investigated. In this study, we
      examined the preemptive effects on administering different doses of Tualang honey
      and prednisolone on the nociceptive response in male Sprague-Dawley rats. Thirty
      five male Sprague-Dawley rats were randomized into five groups (n = 7) and each
      group received either distilled water, Tualang honey (0.2, 1.2 or 2.4 g/kg) or
      prednisolone (10 mg/kg) for 10 days. The response to noxious thermal stimulus was
      assessed using tail flick test on Day 10. The well-being of the rats was also
      assessed by monitoring their food intake and body weight. Data were analyzed
      using one-way Analysis of Variance (ANOVA) with post-hoc Scheffe's test and P
      value less than 0.05 was considered significant. In tail flick test, the tail
      flick latency time was significantly higher in the groups that received 1.2 g/kg
      and 2.4 g/kg of Tualang honey and 10 mg/kg of prednisolone, compared to the
      control group (P < 0.05). There was significant reduction in the total food
      pellet intake in the groups receiving prednisolone and Tualang honey (1.2 g/kg
      and 2.4 g/kg) compared to controls; however, the body weight gain was only
      significantly reduced in the prednisolone group. All the parameters were not
      significantly affected in the group receiving 0.2 g/kg of Tualang honey. In
      conclusion, preemptive administration of Tualang honey (1.2 g/kg and 2.4 g/kg)
      and prednisolone (10 mg/kg) had reduced the pain responses. The reduced weight
      gain in the prednisolone group is an unwanted effect due to its metabolic and
      central actions. Further studies are required to confirm the antinociceptive
      effects and elucidate the mechanism of antinociceptive action of Tualang honey in
      the rats. 

PMID- 25379477
TI  - In the memory of Professor Felicidad Cua-Lim.

PMID- 25379479
TI  - Hypersensitivity to pollen of four different species of Brassica: a clinico
      immunologic evaluation in patients of respiratory allergy in India.
AB  - BACKGROUND: Rapeseed-mustard is the second most important source of edible oil in
      India. Several species of Brassica are grown in different parts of country for
      its oilseeds. OBJECTIVE: The objective was to investigate allergenicity to
      antigenic extracts of pollen of 4 species of Brassica. METHODS: Brassica
      campestris, Brassica juncea, Brassica nigra, and Brassica napus were selected for
      the detailed investigation. Pollen samples from each of the four species were
      collected from the polliniferous materials. The antigenic and allergenic profiles
      of these extracts were evaluated by means of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, Skin prick test, enzyme linked immuno sorbent
      assay and Western blot on atopic individuals. RESULTS: Out of the 159 atopic
      subjects tested, 21.38% were positive to at least one or other species of
      Brassica pollen, with highest skin positivity (13.20%) to B. campestris extract.
      Raised IgE with significant linear correlation with intensity of skin reactions
      was obtained. Protein fractions of 20, 25, 32, 37, 56, and 90 kDa were recognized
      by B. campestris and B. juncea whereas 56, 76, 87, and 90 kDa were recognized by
      B. nigra and B. napus as major IgE binding protein fractions. The patients also
      showed positivity to other inhalant pollen allergens tested. CONCLUSION: IgE
      mediated hypersensitivity varied from 4.40% to 13.20% in Indian atopic subjects
      to pollen of one or the other species of Brassica. Protein fractions of 47, 56,
      76, 87, and 90 kDa were identified as IgE binding by all the four species,
      however individual heterogeneity exists. Thus a local species may be more
      pertinent for immunotherapy. The major allergen needs to be further
      characterized.

PMID- 25379478
TI  - Role of inflammasome activation in development and exacerbation of asthma.
AB  - Human airways contact with pathogen-associated molecular patterns and danger
      associated molecular patterns present in many environments. Asthmatic's airways
      may be more susceptible to these patterns and lead to inflammasome activation;
      however, the participation of inflammasome in the development and exacerbation of
      asthma is not fully understood and remains controversial. Asthma is a
      heterogeneous group composed of different airway inflammation patterns with
      different underlying immune mechanisms. One mechanism is neutrophilic airway
      inflammation based on the axis of inflammasome activation, interleukin (IL)
      1beta/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and
      neutrophilic inflammation. The role of inflammasome activation has been
      highlighted in experimental asthma models and some evidence of inflammasome
      activation has been recently demonstrated in human neutrophilic asthmatic
      airways. In addition to caspase-1 activation, proteinase 3 and other protease
      from activated neutrophils directly cleave pro-IL-1beta and pro-IL-18 to IL-1beta
      and IL-18, which contribute to the phenotype of subsequent adaptive immune
      responses without inflammasome activation. Data suggests that neutrophilics in
      asthmatic airways may have an additional effect in initiating inflammasome
      activation and amplifying immune responses. Among the mediators from neutrophils,
      S100A9 seems to be one candidate mediator to explain the action of neutrophils in
      amplifying the airway inflammation in concert with inflammasome. 

PMID- 25379480
TI  - Study of serum interleukin (IL) 18 and IL-6 levels in relation with the clinical
      disease severity in chronic idiopathic urticaria patients of Kashmir (North
      India).
AB  - BACKGROUND: Chronic urticaria is termed as idiopathic if there is an absence of
      any identifiable causes of mast cell and basophil degranulation. Various
      cytokines have been found to be involved in inflammatory processes associated
      with chronic idiopathic urticaria, including interleukin (IL) 18 and IL-6.
      OBJECTIVE: To evaluate any possible correlation of IL-18 and IL-6 cytokines with
      the clinical disease severity in chronic idiopathic urticaria (CIU). METHODS: IL
      18 and IL-6 levels of CIU patients (n = 62) and healthy controls (n = 27) were
      assessed by commercially available enzyme linked immunosorbent assay kits
      following the manufacturer's protocols. RESULTS: Serum IL-18 concentration (mean
      +/- standard deviation [SD], 62.95 +/- 36.09 pg/mL) in CIU patients and in
      healthy controls (54.35 +/- 18.45 pg/mL) showed no statistical significance (p >
      0.05). No statistically significant difference (p > 0.05) was observed between
      autologous serum skin test (ASST) positive and ASST negative patients with regard
      to the serum IL-18 levels either. Similarly, serum IL-6 concentration (0.82 +/-
      4.6 pg/mL) in CIU patients and in healthy controls (0.12 +/- 1.7 pg/mL), showed
      no statistical significance (p > 0.05). Also, comparison between positive and
      ASST negative patients with regard to the serum IL-6 levels was statistically
      nonsignificant (p > 0.05). However, statistical significance was found both in IL
      18 and IL-6 concentrations in certain grades with regard to the clinical disease
      severity of urticaria. CONCLUSION: There is no significant association as such
      found between IL-18 and IL-6 levels with CIU, however, these cytokines may help
      in predicting the clinical disease severity in CIU. Hence, these cytokines may
      indicate a potential role as a biomarker to assess the disease severity in CIU.

PMID- 25379481
TI  - Innate lymphoid cells and cytokines of the novel subtypes of helper T cells in
      asthma.
AB  - BACKGROUND: In this study, the expression of interleukin-9 (IL-9), IL-17, IL-22,
      and IL-25 genes that might be the potential predisposing factors for asthma as
      well as count of innate lymphoid cells (ILCs) as another source of inflammatory
      cytokines have been evaluated. OBJECTIVE: The aim of this study was to evaluate
      the expression of newly identified helper T cells signature cytokines and amount
      of ILCs. METHODS: Blood and sputum samples from 23 patients with moderate to
      severe asthma and 23 healthy volunteers were collected. The types of allergens to
      which our patients were sensitive were defined using immunoblotting method. Gene
      expression of studied cytokines was evaluated using quantitative transcription
      polymerase chain reaction and ILCs were counted by the flow cytometry method.
      RESULTS: In this research, the gene expressions of IL-9, IL-17, IL-22, and IL-25
      were significantly higher in asthmatics, especially in the severe form of the
      disease. This increase was even higher in serum samples compared with sputum
      samples. Counting ILCs revealed their increase in comparison with normal people.
      CONCLUSION: We showed the importance of IL-25, IL-22, IL-17, and IL-9 cytokines
      in patients with asthma as their expression levels are increased and these
      increase are correlated with the severity of the disease. We also showed that the
      increased amount of ILCs in asthmatics could confirm their potential role in the
      immunopathogenesis of asthma as another source of inflammatory cytokines.

PMID- 25379482
TI  - The impact of sinusitis on the long-term clinical outcomes of asthma.
AB  - BACKGROUND: Upper respiratory diseases have been linked with lower respiratory
      diseases. However, the long-term effect of sinusitis on the clinical outcomes of
      asthma has not been fully evaluated. OBJECTIVE: The aim of this study was to
      investigate the impact of sinusitis on the disease progression of asthma.
      METHODS: Seventy-five asthmatic patients confirmed with the methacholine
      bronchial provocation test or bronchodilator response were included. The study
      patients underwent paranasal sinus x-ray upon their asthma evaluation and they
      visited the hospital at least 3 years or longer. We retrospectively reviewed
      their medical records and compared data according to the presence of comorbid
      sinusitis. RESULTS: Among the 75 asthmatic subjects, 38 subjects (50.7%) had
      radiologic evidence of sinusitis. Asthmatics with sinusitis had significantly
      lower forced expiratory volume in 1 second (FEV1; 79.2% vs. 88.2%) and PC20
      values (5.2 mg/mL vs. 8.9 mg/mL) compared to asthmatics without sinusitis at the
      time of diagnosis. This difference in FEV1 disappeared (82.6% vs. 87.2%) in the 3
      year follow-up, although FEV1 was more variable (31.7% vs. 23.5%) and worst FEV1
      was also significantly lower in patients with sinusitis compared to those without
      (70.9% vs. 79.0%). There were no significant differences in the number of
      hospital visits, acute exacerbations, and scores for the asthma control test.
      CONCLUSION: Although sinusitis was associated with lower baseline lung function
      and higher hyperreactivity, sinusitis was not related with significant
      deterioration in lung function over 3 years of follow-up. Asthmatics with
      sinusitis showed more variability in lung function during the follow-up period.
      Healthcare utilization was not different except antibiotics use.

PMID- 25379483
TI  - The role of antiseptic agents in atopic dermatitis.
AB  - The skin of individuals with atopic dermatitis has a susceptibility to be
      colonized with Staphylococcus aureus. This has been associated with increased
      frequency and severity of exacerbations of atopic dermatitis. Therefore, there is
      a growing interest in the use of antiseptic agents to target primary bacterial
      colonization and infection. Antiseptic agents have been found to be better
      tolerated and less likely to induce bacterial resistance as compared to
      antibiotics. There is also a wide variety of antiseptic agents available. The
      efficacy of antiseptic agents has yet to be established as the studies reviewed
      previously have been small and of suboptimal quality. This review discusses the
      rationale behind targeting S. aureus with antiseptic agents and presents findings
      from a review of studies assessing the efficacy of antiseptics in atopic
      dermatitis in the last five years. Four studies were found, including a bleach
      bath study which has already been reviewed elsewhere. The remaining 3 studies
      assessed the efficacy of sodium hypochlorite containing cleansing body wash,
      sodium hypochlorite baths and 1% triclosan in leave on emollient. These studies
      suggested some benefit for the inclusion of antiseptic use with the mainstay
      management of atopic dermatitis, including a potential steroid sparring effect.
      However, there are many limitations to these studies which therefore warrant
      further investigation on the impact of antiseptic use in atopic dermatitis. 

PMID- 25379484
TI  - House dust mite allergy: environment evaluation and disease prevention.
AB  - There are two groups of dust mites, house dust mites (HDMs) and storage mites
      (SMs), that have been identified in the household environment. Both could induce
      airway inflammation through activation of innate and adaptive immunity and lead
      to asthma. In order to monitor environmental dust mite infestation, different
      methods can be used to detect their presence, such as the use of floating
      methods, monoclonal antibodies, and nanostructured biosensor. SM could be
      identified in the storage room, mainly in contaminated food such as mushrooms and
      corn starch. In HDM-sensitive subjects and mice that were challenged with HDM or
      SM after sensitization, these mites could up-regulate IgE levels, T helper 2
      associated cytokine production and airway hypersensitivity. Different age groups
      of subjects were sensitized by different species of mites. More subjects above 70
      years were sensitized by SM and more subjects below the age of 40 years were
      sensitized to HDM. Different allergenic components of dust mite extracts, such as
      Der p 1, Der p 2, could activate innate immunity through activating pattern
      recognition receptor (PRR) and then lead to allergic inflammation. The best
      modality to treat HDM allergy is immunomodulation through Treg cells and IgA
      production. In the recent years, many studies indicated probiotics could increase
      IgA secretion and the number of Treg cells. However, some studies conducted in
      adults have contradictory effects in reducing allergic symptoms. Therefore,
      probiotics confer inconclusive benefits on the allergic symptoms. 

PMID- 25379485
TI  - Lamotrigine-induced toxic epidermal necrolysis confirmed by in vitro granulysin
      and cytokine assays.
AB  - Lamotrigine is a recent medication which is prescribed for various
      neuropsychiatric conditions. It is generally well-tolerated, but recent
      pharmacoepidemiological evidence suggests that lamotrigine is associated with
      risks of developing severe cutaneous drug reactions like toxic epidermal
      necrolysis (TEN). However, there still remains the diagnostic challenge regarding
      how to confirm the drug causality in suspected cases. In most cases so far,
      lamotrigine causality has not been objectively demonstrated, which was possibly
      due to high risk of oral challenge tests or the lack of useful in vitro drug
      assays. Here we report a case of lamotrigine-induced TEN, of which the drug
      causality was confirmed by in vitro granulysin and cytokine assays. 

PMID- 25379486
TI  - Successful management of severe cow's milk allergy with omalizumab treatment and
      CD-sens monitoring.
AB  - Food allergy is common in children and young adults and may be difficult to
      diagnose and is at present treated with avoidance of the food in question. The
      aim of this report is to share our clinical experiences monitoring omalizumab
      treatment by basophil allergen threshold sensitivity, CD-sens. Five children, 6
      16 years of age, with a severe milk allergy including episodes of anaphylaxis and
      IgE-antibodies, between 30 and 160 kUA/L to casein and alpha-lactalbumin (milk
      proteins), were treated with omalizumab. CD-sens, was tested prior to and after 4
      months of omalizumab and if turned negative, it was followed by an oral milk
      challenge. All children became negative in CD-sens and had a negative milk
      challenge, but one child required doubling of the omalizumab dose to achieve a
      negative CD-sens before a challenge was done. Omalizumab appears useful in
      treatment of severe food allergy, e.g., anaphylaxis to milk, and CD-sens
      monitoring may decide when and how to perform a food challenge. 

PMID- 25379487
TI  - Comparison of the Effects of 1 Hz and 20 Hz rTMS on Motor Recovery in Subacute
      Stroke Patients.
AB  - OBJECTIVE: To compare the low frequency (1 Hz) repetitive transcranial magnetic
      stimulation (rTMS) with high frequency (20 Hz) rTMS on motor functional
      improvement of the affected upper extremity in subacute stroke patients. METHODS:
      Forty patients with subacute ischemic stroke participated in this study. The
      first group received 10 sessions of 20 Hz rTMS at ipsilesional M1 area and the
      other group received 10 sessions of 1 Hz rTMS at contralesional M1 area. Motor
      training of the hemiparetic hand was conducted after each rTMS train. All the
      patients received conventional occupational therapy immediately after each rTMS
      session. Manual function test (MFT), Fugl-Meyer Assessment scale (FMS), Modified
      Barthel Index (MBI), Brunnstrom recovery stage, and grip strength were used to
      assess motor function before, at the end of, and one month after the last session
      of rTMS. RESULTS: No adverse side effects were reported during the course of the
      experiment using rTMS. No significant difference in motor function of the
      affected upper extremity was observed between the two groups before rTMS.
      Significant improvements in MFT, FMS, MBI, and Brunnstrom stage were observed in
      the both groups at the end of the last rTMS session and one month later (p<0.05).
      No significant difference was found between the two groups (p>0.05). CONCLUSION:
      There was no significant difference in motor function of the affected upper
      extremity between 1 Hz and 20 Hz rTMS during the subacute period of ischemic
      stroke. Thus, we cannot conclude which has a greater effect.

PMID- 25379488
TI  - Effect of Low-Frequency rTMS and NMES on Subacute Unilateral Hemispheric Stroke
      With Dysphagia.
AB  - OBJECTIVE: To investigate the effect of low-frequency repetitive transcranial
      magnetic stimulation (rTMS) and neuromuscular electrical stimulation (NMES) on
      post-stroke dysphagia. METHODS: Subacute (<3 months), unilateral hemispheric
      stroke patients with dysphagia were randomly assigned to the conventional
      dysphagia therapy (CDT), rTMS, or NMES groups. In rTMS group, rTMS was performed
      at 100% resting motor threshold with 1 Hz frequency for 20 minutes per session (5
      days per week for 2 weeks). In NMES group, electrical stimulation was applied to
      the anterior neck for 30 minutes per session (5 days per week for 2 weeks). All
      three groups were given conventional dysphagia therapy for 4 weeks. We evaluated
      the functional dysphagia scale (FDS), pharyngeal transit time (PTT), the
      penetration-aspiration scale (PAS), and the American Speech-Language Hearing
      Association National Outcomes Measurement System (ASHA NOMS) swallowing scale at
      baseline, after 2 weeks, and after 4 weeks. RESULTS: Forty-seven patients
      completed the study; 15 in the CDT group, 14 in the rTMS group, and 18 in the
      NMES group. Mean changes in FDS and PAS for liquid during first 2 weeks in the
      rTMS and NMES groups were significantly higher than those in the CDT group, but
      no significant differences were found between the rTMS and NMES group. No
      significant difference in mean changes of FDS and PAS for semi-solid, PTT, and
      ASHA NOMS was observed among the three groups. CONCLUSION: These results
      indicated that both low-frequency rTMS and NMES could induce early recovery from
      dysphagia; therefore, they both could be useful therapeutic options for dysphagic
      stroke patients.

PMID- 25379489
TI  - Retrospective assessment of the implementation of critical pathway in stroke
      patients in a single university hospital.
AB  - OBJECTIVE: To evaluate the effects of the implementation of critical pathway (CP)
      in stroke patients treated at a single university hospital. METHODS: A
      retrospective medical review collected data from 497 patients who had suffered
      acute stroke in the rehabilitation center. Stroke outcomes were compared between
      before and after the implementation of CP based on factors including demographic
      factors, stroke characteristics, pre-existing medical conditions, medical
      complications, functional states, and length of stay (LOS). RESULTS: After the
      implementation of CP, the patients showed significantly higher stage for upper
      proximal (p=0.008) and lower extremity (p=0.001) on Brunnstrom stage and
      significantly lower scores for modified Rankin Scale (p=0.003) at transfer. For
      those with pre-existing medical conditions, there were significantly increased
      osteoarthritis (p=0.002) and valvular heart disease (p=0.011). Regarding medical
      complications during acute inpatient rehabilitation, there were significantly
      decreased shoulder pain (p=0.001) and dysphagia (p=0.017), and significantly
      increased gastrointestinal symptoms (p=0.001). Functional gain and efficiency of
      stroke patients during rehabilitation center hospitalization did not
      significantly change after implementation of CP. But, shorter LOS of total
      hospitalization, pre-rehabilitation center hospitalization, and rehabilitation
      center hospitalization were evident. CONCLUSION: After the implementation of CP,
      patients less often developed complications and displayed no changes in
      functional gain and efficiency. They had shorter LOS of total hospitalization,
      pre-rehabilitation center hospitalization and rehabilitation center
      hospitalization.

PMID- 25379490
TI  - Cutoff value of pharyngeal residue in prognosis prediction after neuromuscular
      electrical stimulation therapy for Dysphagia in subacute stroke patients.
AB  - OBJECTIVE: To determine the cutoff value of the pharyngeal residue for predicting
      reduction of aspiration, by measuring the residue of valleculae and pyriformis
      sinuses through videofluoroscopic swallowing studies (VFSS) after treatment with
      neuromuscular electrical stimulator (VitalStim) in stroke patients with
      dysphagia. METHODS: VFSS was conducted on first-time stroke patients before and
      after the VitalStim therapy. The results were analyzed for comparison of the
      pharyngeal residue in the improved group and the non-improved group. RESULTS: A
      total of 59 patients concluded the test, in which 42 patients improved well
      enough to change the dietary methods while 17 did not improve sufficiently.
      Remnant area to total area (R/T) ratios of the valleculae before treatment in the
      improved group were 0.120, 0.177, and 0.101 for solid, soft, and liquid foods,
      respectively, whereas the ratios for the non-improved group were 0.365, 0.396,
      and 0.281, respectively. The ratios of the pyriformis sinuses were 0.126, 0.159,
      and 0.121 for the improved group and 0.315, 0.338, and 0.244 for the non-improved
      group. The R/T ratios of valleculae and pyriformis sinus were significantly lower
      in the improved group than the non-improved group in all food types before
      treatment. The R/T ratio cutoff values were 0.267, 0.250, and 0.185 at valleculae
      and 0.228, 0.218, and 0.185 at pyriformis sinuses. CONCLUSION: In dysphagia after
      stroke, less pharyngeal residue before treatment serves as a factor for
      predicting greater improvement after VitalStim treatment.

PMID- 25379491
TI  - White matter hyperintensities and cognitive dysfunction in patients with
      infratentorial stroke.
AB  - OBJECTIVE: To determine whether cognitive function is associated with white
      matter hyperintensities (WMH) in patients with infratentorial stroke. METHODS:
      This was a retrospective, cross-sectional study. Twenty-four first-ever
      infratentorial stroke patients between 18 and 60 years of age were enrolled. WMH
      was evaluated by the Fazekas scale and the Scheltens scale. Cognitive functions
      were assessed using the Korean Mini-Mental Status Examination (K-MMSE), Rey
      Osterrieth Complex Figure Test, and the Seoul Computerized Neuropsychological
      Test Battery (SCNT) at one month after stroke. All participants were divided into
      two groups based on the presence of WMH (no-WMH group and WMH group). General
      characteristics and cognitive functions were compared between the groups.
      RESULTS: There were no significant differences in general characteristics, such
      as age, stroke type, hypertension history, and education level between the two
      groups. However, K-MMSE in the WMH group was significantly lower compared to the
      no-WMH group (p<0.05). The verbal learning test score in SCNT was significantly
      higher in the no-WMH group compared to the WMH group (p<0.05). Executive function
      in the no-WMH group tended to be higher compared to the WMH group. CONCLUSION:
      Impairment of cognitive function in patients with infratentorial stroke appeared
      to be associated with WMH. WMH should be carefully evaluated during
      rehabilitation of infratentorial stroke patients.

PMID- 25379492
TI  - Cardiovascular response during submaximal underwater treadmill exercise in stroke
      patients.
AB  - OBJECTIVE: To evaluate the cardiovascular response during head-out water
      immersion, underwater treadmill gait, and land treadmill gait in stroke patients.
      METHODS: Ten stroke patients were recruited for underwater and land treadmill
      gait sessions. Each session was 40 minutes long; 5 minutes for standing rest on
      land, 5 minutes for standing rest in water or on treadmill, 20 minutes for
      treadmill walking in water or on land, 5 minutes for standing rest in water or on
      treadmill, and 5 minutes for standing rest on land. Blood pressure (BP) and heart
      rate (HR) were measured during each session. In order to estimate the
      cardiovascular workload and myocardial oxygen demand, the rate pressure product
      (RPP) value was calculated by multiplying systolic BP (SBP) by HR. RESULTS: SBP,
      DBP, mean BP (mBP), and RPP decreased significantly after water immersion, but HR
      was unchanged. During underwater and land treadmill gait, SBP, mBP, DBP, RPP, and
      HR increased. However, the mean maximum increases in BP, HR and RPP of underwater
      treadmill walking were significantly lower than that of land treadmill walking.
      CONCLUSION: Stroke patients showed different cardiovascular responses during
      water immersion and underwater gait as opposed to standing and treadmill-walking
      on land. Water immersion and aquatic treadmill gait may reduce the workload of
      the cardiovascular system. This study suggested that underwater treadmill may be
      a safe and useful option for cardiovascular fitness and early ambulation in
      stroke rehabilitation.

PMID- 25379493
TI  - Post-polio syndrome and risk factors in korean polio survivors: a baseline survey
      by telephone interview.
AB  - OBJECTIVE: To obtain information on the socioeconomic, medical, and functional
      status of polio survivors, and to use these results as the preliminary data for
      establishing the middle-aged cohort of polio survivors. METHODS: The subjects
      were recruited based on the medical records of multiple hospitals and centers.
      They were assessed through a structured questionnaire over the phone. Post
      poliomyelitis syndrome (PPS) was identified according to the specified diagnostic
      criteria. Differences between polio survivors with or without PPS were evaluated,
      and the risk factors for PPS were analyzed by the odds ratio (OR). RESULTS:
      Majority of polio survivors were middle-aged and mean age was 51.2+/-8.3 years. A
      total of 188 out of 313 polio survivors met the adopted criteria for PPS based on
      the symptoms, yielding a prevalence of 61.6%. Mean interval between acute
      poliomyelitis and the development of PPS was 38.5+/-11.6 years. Female gender (OR
      1.82; confidence interval [CI] 1.09-3.06), the age at onset of poliomyelitis (OR
      1.75; CI 1.05-2.94), the use of orthoses or walking aids (OR 2.46; CI 1.44-4.20),
      and the history of medical treatment for paralysis, pain or gait disturbance (OR
      2.62; CI 1.52-4.51) represented independent risk factors for PPS. CONCLUSION: We
      found that the majority of Korean polio survivors entered middle age with many
      medical, functional, and social problems. Female gender, early age of onset of
      poliomyelitis, the use of orthoses or walking aids, and the history of medical
      treatment for paralysis, pain or gait disturbance were identified as the
      significant risk factors for PPS. A comprehensive and multidisciplinary plan
      should be prepared to manage polio survivors considering their need for health
      care services and the risk factors for late effects, such as PPS.

PMID- 25379494
TI  - The effect of two different hand exercises on grip strength, forearm
      circumference, and vascular maturation in patients who underwent arteriovenous
      fistula surgery.
AB  - OBJECTIVE: To compare the effect of two different hand exercises on hand strength
      and vascular maturation in patients who underwent arteriovenous fistula surgery.
      METHODS: We recruited 18 patients who had chronic kidney disease and had
      undergone arteriovenous fistula surgery for hemodialysis. After the surgery, 10
      subjects performed hand-squeezing exercise with GD Grip, and other 8 subjects
      used Soft Ball. The subjects continued the exercises for 4 weeks. The hand grip
      strength, pinch strength (tip, palmar and lateral pinch), and forearm
      circumference of the subjects were assessed before and after the hand-squeezing
      exercise. The cephalic vein size, blood flow velocity and volume were also
      measured by ultrasonography in the operated limb. RESULTS: All of the 3 types of
      pinch strengths, grip strength, and forearm circumference were significantly
      increased in the group using GD Grip. Cephalic vein size and blood flow volume
      were also significantly increased. However, blood flow velocity showed no
      difference after the exercise. The group using Soft Ball showed a significant
      increase in the tip and lateral pinch strength and forearm circumference. The
      cephalic vein size and blood flow volume were also significantly increased. On
      comparing the effect of the two different hand exercises, hand-squeezing exercise
      with GD Grip had a significantly better effect on the tip and palmar pinch
      strength than hand-squeezing exercise with Soft Ball. The effect on cephalic vein
      size was not significantly different between the two groups. CONCLUSION: The
      results showed that hand squeezing exercise with GD Grip was more effective in
      increasing the tip and palmar pinch strength compared to hand squeezing exercise
      with soft ball.

PMID- 25379495
TI  - Reduction of Continuous Theta Burst Stimulation-Induced Motor Plasticity in
      Healthy Elderly With COMT Val158Met Polymorphism.
AB  - OBJECTIVE: To delineate whether cortical plasticity induced by continuous theta
      burst stimulation (cTBS) differed according to catechol-O-methyltransferase
      (COMT) gene polymorphism in healthy older adults. METHODS: Eighteen healthy older
      volunteers (mean age 73.78+/-5.04; 12 females and 6 males) were recruited.
      Volunteers randomly assigned in either a sham-first or real cTBS first group
      participated in two separate TMS visits with at least a 2-day wash-out period.
      Genotyping was carried out at baseline by a separate researcher who was blinded.
      cTBS was delivered in a hot spot over M1 at an active motor threshold of 80%.
      Motor evoked potentials (MEPs) were obtained at 120% of the resting motor
      threshold before and after sham/cTBS. RESULTS: The relative MEP to baseline was
      significantly decreased 0 and 10 minutes post-stimulation and increased 40
      minutes post-stimulation, as compared with the sham condition. Immediately after
      cTBS, the Val/Val group had a significantly reduced relative MEP value, as
      compared with the MET carrier group. CONCLUSION: In healthy older persons, cTBS
      induced motor plasticity was reduced in the COMT Val/Val group as compared with
      the (158)Met carrier group.

PMID- 25379496
TI  - Correlations Between Electrically Quantified Pain Degree, Subjectively Assessed
      Visual Analogue Scale, and the McGill Pain Questionnaire: A Pilot Study.
AB  - OBJECTIVE: To evaluate the clinical utility of the electrically calculated
      quantitative pain degree (QPD) and to correlate it with subjective assessments of
      pain degree including a visual analogue scale (VAS) and the McGill Pain
      Questionnaire (MPQ). METHODS: We recruited 25 patients with low back pain. Of
      them, 21 patients suffered from low back pain for more than 3 months. The QPD was
      calculated using the PainVision (PV, PS-2100; Nipro Co., Osaka, Japan). We
      applied electrodes to the medial forearm of the subjects and the electrical
      stimulus was amplified sequentially. Minimum perceived current (MPC) and pain
      equivalent current (PEC) were defined as minimum electrical stimulation that
      could be sensed by the subject and electrical stimulation that could trigger
      actual pain itself. To eliminate individual differences, we defined QPD as the
      following: QPD=PEC-MPC/MPC. We scored pre-treatment QPD three times at admission
      and post-treatment QPD once at discharge. The VAS, MPQ, and QPD were evaluated
      and correlations between the scales were analyzed. RESULTS: Result showed
      significant test-retest reliability (ICC=0.967, p<0.001) and the correlation
      between QDP and MPQ was significant (at admission SRCC=0.619 and p=0.001; at
      discharge SRCC=0.628, p=0.001). However, the correlation between QPD and VAS was
      not significant (at admission SRCC=0.240, p=0.248; at discharge SRCC=0.289,
      p=0.161). CONCLUSION: Numerical values measured with PV showed consistent results
      with repeated calculations. Electrically measured QPD showed an excellent
      correlation with MPQ but not with VAS. These results demonstrate that PV is a
      significantly reliable device for quantifying the intensity of low back pain.

PMID- 25379497
TI  - Ultrasound-guided myofascial trigger point injection into brachialis muscle for
      rotator cuff disease patients with upper arm pain: a pilot study.
AB  - OBJECTIVE: To assess the efficacy of trigger point injection into brachialis
      muscle for rotator cuff disease patients with upper arm pain. METHODS: A
      prospective, randomized, and single-blinded clinical pilot trial was performed at
      university rehabilitation hospital. Twenty-one patients clinically diagnosed with
      rotator cuff disease suspected of having brachialis myofascial pain syndrome
      (MPS) were randomly allocated into two groups. Effect of ultrasound (US)-guided
      trigger point injection (n=11) and oral non-steroidal anti-inflammatory drug
      (NSAID) (n=10) was compared by visual analog scale (VAS). RESULTS: US-guided
      trigger point injection of brachialis muscle resulted in excellent outcome
      compared to the oral NSAID group. Mean VAS scores decreased significantly after 2
      weeks of treatment compared to the baseline in both groups (7.3 vs. 4.5 in the
      injection group and 7.4 vs. 5.9 in the oral group). The decrease of the VAS score
      caused by injection (DVAS=-2.8) was significantly larger than caused by oral
      NSAID (DVAS=-1.5) (p<0.05). CONCLUSION: In patients with rotator cuff disease, US
      guided trigger point injection of the brachialis muscle is safe and effective for
      both diagnosis and treatment when the cause of pain is suspected to be originated
      from the muscle.

PMID- 25379498
TI  - Analgesic effect of intrathecal gabapentin in a rat model of persistent muscle
      pain.
AB  - OBJECTIVE: To evaluate the analgesic effect of intrathecal gabapentin therapy on
      secondary hyperalgesia in a rat model of persistent muscle pain. METHODS:
      Intrathecal catheters were implanted into rats. Mechanical secondary hyperalgesia
      was induced by repeated intramuscular injections of acidic solution into the
      gastrocnemius muscle. Gabapentin was administrated intrathecally. Rats were
      allocated to control and experimental (gabapentin 30, 100, 300, and 1,000 ug)
      group. After gabapentin administration, mechanical withdrawal threshold was
      measured every 15 minutes and the motor function was measured 30 minutes later.
      RESULTS: Mechanical hyperalgesia was evoked after the second acidic buffer
      injection. There was a significant improvement on the mechanical threshold after
      administration of 100, 300, and 1,000 ug gabapentin compared to pre-injection and
      the control group. The analgesic effect continued for 105, 135, and 210 minutes,
      respectively. To discern side effects, motor function was measured. Motor
      function was preserved in both groups after gabapentin administration, except for
      rats who received 1,000 ug gabapentin. CONCLUSION: Intrathecal gabapentin
      administration produces dose-dependent improvements in mechanical hyperalgesia in
      a persistent muscle pain rat model. This implicates the central nervous system as
      having a strong influence on the development of persistent mechanical
      hyperalgesia. These results are helpful in understanding the pathophysiology of
      secondary hyperalgesia and in the treatment of patients with chronic muscle pain.

PMID- 25379499
TI  - Occipital condyle fracture with isolated unilateral hypoglossal nerve palsy.
AB  - Occipital condyle fractures (OCFs) with selective involvement of the hypoglossal
      canal are rare. OCFs usually occur after major trauma and combine multiple
      fractures. We describe a 38-year-old man who presented with neck pain and a
      tongue deviation to the right side after a traffic accident. Severe limitations
      were detected during active and passive range of neck motion in all directions. A
      physical examination revealed a normal gag reflex and normal mobility of the
      palate, larynx, and shoulder girdle. He had normal taste and general sensation in
      his tongue. However, he presented with a tongue deviation to the right side on
      protrusion. A videofluoroscopic swallowing study revealed piecemeal deglutition
      due to decreased tongue mobility but no aspiration of food. Plain X-ray film
      findings were negative, but a computed tomography study with coronal
      reconstruction demonstrated a right OCF involving the hypoglossal canal. An
      electrodiagnostic study revealed evidence of right hypoglossal nerve palsy. We
      report a rare case of isolated hypoglossal nerve palsy caused by an OCF. 

PMID- 25379500
TI  - Effect of ultrasonography-guided botulinum toxin type a injection in holmes'
      tremor secondary to pontine hemorrhage: case report.
AB  - Holmes' tremor is a low-frequency rest and intentional tremor secondary to
      various insults, including cerebral ischemia, hemorrhage, trauma, or neoplasm.
      Pharmacologic treatment is usually unsuccessful, and some cases require surgical
      intervention. We report a rare case of Holmes' tremor secondary to left pontine
      hemorrhage in a 29-year-old Asian male patient who developed 1.6-Hz postural and
      rest tremor of the right hand. He responded markedly to ultrasonography-guided
      botulinum toxin type A injection. To our knowledge, this is the first report of
      Homes' tremor treated with ultrasonography-guided botulinum toxin type A
      injection with favorable results. 

PMID- 25379501
TI  - Cerebral venous sinus thrombosis and venous hemorrhagic infarction in a young
      woman.
AB  - Cerebral venous sinus thrombosis (CVST) is an uncommon cause of cerebral
      infarction, compared to arterial diseases. It is often unrecognized at initial
      presentation due to the diversity of causes and clinical manifestations. A 29
      year-old female patient complained of severe headache and presented at the
      emergency room with altered consciousness. Brain computed tomography and brain
      magnetic resonance image revealed the left sigmoid sinus thrombosis with venous
      hemorrhagic infarction (VHI) in the left temporal lobe. The patient had no past
      medical and family history of bleeding diathesis. The laboratory finding at the
      admission showed severe iron-deficiency anemia (IDA), and protein C and S
      activities were decreased. After the neurosurgery, iron replacement, and
      neurorehabilitation, the patient had a good recovery. There has been no known
      recurrence. We report our therapeutic intervention on a very rare case of CVST
      and VHI, with IDA as a probable cause of cerebral thrombosis. 

PMID- 25379502
TI  - Locked-in Syndrome due to Central Pontine Myelinolysis: Case Report.
AB  - Central pontine myelinolysis (CPM) classically occurs in alcoholics, malnourished
      individuals, chronic liver diseases, and rapid correction of hyponatremia. This
      report presents locked-in syndrome due to CPM following rapid correction of
      hyponatremia. A 44-year-old male came to the hospital due to a short period of
      loss of consciousness. He was alert and had no focal neurological abnormalities
      at admission. The serum sodium concentration was 118 mEq/L and was corrected to
      134 mEq/L in the first 18 hours. One week later, progressive weakness in limbs
      developed and he progressed to a complete quadriplegic state and bulbar palsy,
      with only eye blinking preserved. Brain magnetic resonance imaging revealed a
      characteristic hyperintense signal abnormality in both pons, so he was diagnosed
      to locked-in syndrome caused by CPM. The patient gradually improved following
      continuous intensive rehabilitation for more than 2 years. He was able to move
      all joint muscles against gravity in generally and he could gait under
      supervision. 

PMID- 25379503
TI  - Usefulness of videofluoroscopic swallow study in treacher collins syndrome with
      cleft palate: a case report.
AB  - A 3-year-old girl had multiple anomalies compatible with Treacher Collins
      Syndrome (TCS). From the neonatal period, sucking was poor, making tube feeding
      necessary. Excessive saliva was retained in the oral cavity. Nasal leakage caused
      by the cleft palate was observed when she spoke. The initial videofluoroscopic
      swallow study (VFSS) showed a poor posterior bolus transit and nasopharyngeal
      regurgitation. A delayed swallow reflex and bolus stasis at the vallecular and
      pyriform sinuses were recognized. Based on the VFSS findings, the patient
      underwent palatoplasty at 20 months of age. At approximately 23 months of age, a
      follow-up VFSS was performed; poor posterior bolus transit, nasopharyngeal
      regurgitation, and delayed swallow reflex were not observed. Finally, the patient
      was able to eat ground or chopped foods and solid foods orally. We deem VFSS to
      be helpful in deciding the appropriate management of dysphagia in TCS. 

PMID- 25379504
TI  - Congenital muscular torticollis concurrent with sagittal synostosis: a case
      report.
AB  - Congenital muscular torticollis (CMT) and craniosynostosis are diseases that
      cause plagiocephaly and craniofacial asymmetry in children. In our literature
      review, we did not find any report of concurrent manifestation of CMT and
      craniosynostosis. A 41-month-old boy visited our hospital with left torticollis,
      right laterocollis, and craniofacial asymmetry as the main findings. During
      clinical examination, prominent right sternocleidomastoid muscle and limited
      range of motion of the neck were noted, and right CMT was confirmed by magnetic
      resonance imaging of the neck. Three-dimensional computed tomography of the
      skull, which was conducted due to the unusual appearance of the skull with a
      large head circumference, mild brachycephaly, as well as left plagiocephaly,
      revealed premature closure of the sagittal suture. Thus, we report the first case
      that showed concurrence of CMT and sagittal synostosis. We recommend that
      concurrently manifested craniosynostosis needs to be examined if the subject with
      CMT displays unusual craniofacial asymmetry to a greater extent than
      deformational plagiocephaly. 

PMID- 25379506
TI  - Opportunities for NanoTheranosis in Lung Cancer and Pulmonary Metastasis.
AB  - Malignancies of the lungs, both primary and metastatic, are the leading cause of
      death worldwide. Over 1.5 million new cases of primary lung cancer are diagnosed
      annually worldwide with a dismal five-year survival rate of approximately 15%,
      which remains unchanged despite major efforts and medical advances. As expected,
      survival for patients with lung metastases is even worse at about 5%. Early
      detection and staging are fundamental in improving survival rates and selecting
      the most effective treatment strategies. Recently, nanoparticles have been
      developed for imaging and treating various cancers, including pulmonary
      malignancies. In this work, three different examples of nanoparticle
      configurations for cancer theranosis are presented, namely conventional spherical
      polymeric nanoparticles with a diameter of ~ 150 nm; and discoidal mesoporous
      silicon nanoconstructs and discoidal polymeric nanoconstructs with a diameter of
      ~ 1,000 nm and a height of 400 and 500 nm, respectively. The spherical
      nanoparticles accumulate in tumors by means of the well-known enhanced permeation
      and retention effect, whereas sub-micrometer discoidal nanoconstructs are
      rationally designed to adhere firmly to the tortuous tumor vasculature. All three
      nanoparticles are characterized for their in vivo performance in terms of
      magnetic resonance, positron-emission tomography (PET), and optical imaging.
      Preliminary data on the in vivo and ex vivo PET/CT imaging of breast cancer
      metastasis in the lungs using discoidal nanoconstructs is presented. In
      conclusion, opportunities for nanoparticle-based theranosis in primary lung
      cancer and pulmonary metastasis are presented and discussed.

PMID- 25379507
TI  - Serum-free medium optimization based on trial design and support vector
      regression.
AB  - The Plackett-Burman design and support vector machine (SVM) were reported to be
      used on many fields such as some feature selections, protein structure
      prediction, or forecasting of other situations. Here, with suspension adapted
      Chinese hamster ovary (CHO) cells as the object of study, a serum-free medium for
      the culture of CHO cells in suspension was optimized by this method. Support
      vector machine based on genetic algorithm was used to predict the growth rate of
      CHO and prove the results from the trial designs. Experimental results indicated
      that ZnSO4, transferrin, and bovine serum albumin (BSA) were important ones. The
      same conclusion was arrived at when the support vector regression model analyzed
      the experimental results. With the methods mentioned, the influence of 7 medium
      supplements on the growth of CHO cells in suspension was evaluated efficiently. 

PMID- 25379509
TI  - A novel approach for development and characterization of effective mosquito
      repellent cream formulation containing citronella oil.
AB  - Citronella essential oil (CEO) has been reported as an excellent mosquito
      repellent; however, mild irritancy and rapid volatility limit its topical
      application. It was aimed to develop a nonirritant, stable, and consistent cream
      of CEO with improved residence time on skin using an industrial approach. Phase
      inversion temperature technique was employed to prepare the cream. It was
      optimized and characterized based on sensorial evaluation, emulsification, and
      consistency in terms of softness, greasiness, stickiness, and pH. The optimum
      batch (B5) was evaluated for viscosity (90249.67+/-139.95 cP), texture profile
      with respect to firmness (38.67+/-0.88 g), spreadability (70.33+/-0.88 mJ), and
      extrudability (639.67+/-8.09+/-0.1 mJ) using texture analyzer along with two most
      popular marketed products selected as reference standard. Subsequently, B5 was
      found to be stable for more than 90 days and showed enhanced duration of mosquito
      repellency as compared to CEO. HS-GC ensured the intactness of CEO in B5.
      Investigated primary irritation index (PII 0.45) positioned B5 into the category
      of irritation barely perceptible. The pronounced texture profile and stability of
      B5 with extended residence time and less PII revealed its potential application
      in industry and offered a promising alternative to the marketed products of
      synthetic origin.

PMID- 25379508
TI  - Chinese medicines induce cell death: the molecular and cellular mechanisms for
      cancer therapy.
AB  - Chinese medicines have long history in treating cancer. With the growing
      scientific evidence of biomedical researches and clinical trials in cancer
      therapy, they are increasingly accepted as a complementary and alternative
      treatment. One of the mechanisms is to induce cancer cell death. Aim. To
      comprehensively review the publications concerning cancer cell death induced by
      Chinese medicines in recent years and provide insights on anticancer drug
      discovery from Chinese medicines. Materials and Methods. Chinese medicines
      (including Chinese medicinal herbs, animal parts, and minerals) were used in the
      study. The key words including "cancer", "cell death", "apoptosis", "autophagy,"
      "necrosis," and "Chinese medicine" were used in retrieval of related information
      from PubMed and other databases. Results. The cell death induced by Chinese
      medicines is described as apoptotic, autophagic, or necrotic cell death and other
      types with an emphasis on their mechanisms of anticancer action. The relationship
      among different types of cell death induced by Chinese medicines is critically
      reviewed and discussed. Conclusions. This review summarizes that CMs treatment
      could induce multiple pathways leading to cancer cell death, in which apoptosis
      is the dominant type. To apply these preclinical researches to clinic application
      will be a key issue in the future. 

PMID- 25379510
TI  - Downregulation of type II diabetes mellitus and maturity onset diabetes of young
      pathways in human pancreatic islets from hyperglycemic donors.
AB  - Although several molecular pathways have been linked to type 2 diabetes (T2D)
      pathogenesis, it is uncertain which pathway has the most implication on the
      disease. Changes in the expression of an entire pathway might be more important
      for disease pathogenesis than changes in the expression of individual genes. To
      identify the molecular alterations in T2D, DNA microarrays of human pancreatic
      islets from donors with hyperglycemia (n = 20) and normoglycemia (n = 58) were
      subjected to Gene Set Enrichment Analysis (GSEA). About 178 KEGG pathways were
      investigated for gene expression changes between hyperglycemic donors compared to
      normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus
      (T2DM) and maturity onset diabetes of the young (MODY) pathways are downregulated
      in hyperglycemic donors, while proteasome and spliceosome pathways are
      upregulated. The mean centroid of gene expression of T2DM and MODY pathways was
      shown to be associated positively with insulin secretion and negatively with
      HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in
      islet function and might be involved in T2D. Also, the study demonstrates that
      gene expression profiles from pancreatic islets can reveal some of the biological
      processes related to regulation of glucose hemostats and diabetes pathogenesis. 

PMID- 25379511
TI  - Transgender Health Disparities: Comparing Full Cohort and Nested Matched-Pair
      Study Designs in a Community Health Center.
AB  - PURPOSE: U.S. health surveillance systems infrequently include measures to
      identify transgender respondents or monitor the health of this underserved and
      marginalized population. METHODS: From 2001-2002, transgender and non-transgender
      adults were sampled at a Massachusetts clinic. Health differences were
      formatively examined by transgender identity using a cross-sectional, clinic
      based sample (n=2,653); and a nested matched-pair subsample (n=155). RESULTS:
      Both designs produced virtually identical findings: (1) the prevalence of HIV,
      substance abuse, and smoking did not differ significantly for transgender and non
      transgender patients; (2) transgender patients were more likely to endorse a
      lifetime suicide attempt and ideation compared to non-transgender patients
      (p<0.05); (3) transgender patients disproportionately reported social stressors
      (violence, discrimination, childhood abuse) relative to non-transgender patients
      (p<0.05). CONCLUSION: Findings suggest that a nested design may provide an
      effective methodology for using clinical data to study transgender health, and
      underscore the need for routine collection of gender identity in clinical
      settings.

PMID- 25379512
TI  - Restrictive vs. non-restrictive composition: a magnetoencephalography study.
AB  - Recent research on the brain mechanisms underlying language processing has
      implicated the left anterior temporal lobe (LATL) as a central region for the
      composition of simple phrases. Because these studies typically present their
      critical stimuli without contextual information, the sensitivity of LATL
      responses to contextual factors is unknown. In this magnetoencephalography (MEG)
      study, we employed a simple question-answer paradigm to manipulate whether a
      prenominal adjective or determiner is interpreted restrictively, i.e., as
      limiting the set of entities under discussion. Our results show that the LATL is
      sensitive to restriction, with restrictive composition eliciting higher responses
      than non-restrictive composition. However, this effect was only observed when the
      restricting element was a determiner, adjectival stimuli showing the opposite
      pattern, which we hypothesise to be driven by the special pragmatic properties of
      non-restrictive adjectives. Overall, our results demonstrate a robust sensitivity
      of the LATL to high level contextual and potentially also pragmatic factors.

PMID- 25379513
TI  - Accounting for biological aggregation in heating and imaging of magnetic
      nanoparticles.
AB  - Aggregation is a known consequence of nanoparticle use in biology and medicine;
      however, nanoparticle characterization is typically performed under the pretext
      of well-dispersed, aqueous conditions. Here, we systematically characterize the
      effects of aggregation on the alternating magnetic field induced heating and
      magnetic resonance (MR) imaging performance of iron oxide nanoparticles (IONPs)
      in non-ideal biological systems. Specifically, the behavior of IONP aggregates
      composed of ~10 nm primary particles, but with aggregate hydrodynamic sizes
      ranging from 50 nm to 700 nm, was characterized in phosphate buffered saline and
      fetal bovine serum suspensions, as well as in gels and cells. We demonstrate up
      to a 50% reduction in heating, linked to the extent of aggregation. To quantify
      aggregate morphology, we used a combination of hydrodynamic radii distribution,
      intrinsic viscosity, and electron microscopy measurements to describe the
      aggregates as quasifractal entities with fractal dimensions in the 1.8-2.0 range.
      Importantly, we are able to correlate the observed decrease in magnetic field
      induced heating with a corresponding decrease in longitudinal relaxation rate
      (R1) in MR imaging, irrespective of the extent of aggregation. Finally, we show
      in vivo proof-of-principle use of this powerful new imaging method, providing a
      critical tool for predicting heating in clinical cancer hyperthermia.

PMID- 25379514
TI  - Antimicrobial susceptibility and genetic characterisation of Burkholderia
      pseudomallei isolated from Malaysian patients.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically
      resistant to many antibiotics. Ceftazidime (CAZ), the synthetic beta-lactam, is
      normally used as the first-line antibiotic therapy for treatment of melioidosis.
      However, acquired CAZ resistance can develop in vivo during treatment with CAZ,
      leading to mortality if therapy is not switched to a different antibiotic(s) in a
      timely manner. In this study, susceptibilities of 81 B. pseudomallei isolates to
      nine different antimicrobial agents were determined using the disk diffusion
      method, broth microdilution test and Etest. Highest percentage of susceptibility
      was demonstrated to CAZ, amoxicillin/clavulanic acid, meropenem, imipenem, and
      trimethoprim/sulfamethoxazole. Although these drugs demonstrated the highest
      percentage of susceptibility in B. pseudomallei, the overall results underline
      the importance of the emergence of resistance in this organism. PCR results
      showed that, of the 81 B. pseudomallei, six multidrug resistant (MDR) isolates
      carried bpeB, amrB, and BPSS1119 and penA genes. Genotyping of the isolates using
      random amplified polymorphic DNA analysis showed six different PCR fingerprinting
      patterns generated from the six MDR isolates clusters (A) and eight PCR
      fingerprinting patterns generated for the remaining 75 non-MDR isolates clusters
      (B). 

PMID- 25379515
TI  - Medical applications of microwave imaging.
AB  - Ultrawide band (UWB) microwave imaging is a promising method for the detection of
      early stage breast cancer, based on the large contrast in electrical parameters
      between malignant tumour tissue and the surrounding normal breast-tissue. In this
      paper, the detection and imaging of a malignant tumour are performed through a
      tomographic based microwave system and signal processing. Simulations of the
      proposed system are performed and postimage processing is presented. Signal
      processing involves the extraction of tumour information from background
      information and then image reconstruction through the confocal method delay-and
      sum algorithms. Ultimately, the revision of time-delay and the superposition of
      more tumour signals are applied to improve accuracy. 

PMID- 25379517
TI  - Patient and doctor delays in smear-negative and smear-positive pulmonary
      tuberculosis patients attending a referral hospital in Istanbul, Turkey.
AB  - OBJECTIVES: To measure delays from onset of symptoms to initiation of treatment
      in patients with smear-negative and smear-positive pulmonary tuberculosis and to
      identify reasons for these delays. METHODS: A total of 136 newly diagnosed
      pulmonary tuberculosis patients were interviewed using a structured
      questionnaire. RESULTS: The patients were divided into two groups. Group 1
      included 65 smear-negative patients. There were 71 smear-positive patients in
      group 2. The median application interval was 10 days in group 1 and 14 days in
      group 2. While 24.6% of the patients had patient delay in group 1, patient delay
      was present in 33.8% of the patients in group 2 (P > 0.05). The median health
      care system interval was 41 days in group 1 and 16 days in group 2 (P < 0.0001).
      The most common reason for patient delay was neglect of symptoms by patient in
      both groups. A low index of suspicion for tuberculosis by physicians was the most
      common reason for doctor delays. CONCLUSIONS: Delays are common problem in smear
      negative and smear-positive pulmonary tuberculosis patients. Delays should be
      reduced to reach an effective tuberculosis control. Education of public and
      physicians about tuberculosis is the most important effort to reduce delays.

PMID- 25379516
TI  - Today prospects for tissue engineering therapeutic approach in dentistry.
AB  - In dental practice there is an increasing need for predictable therapeutic
      protocols able to regenerate tissues that, due to inflammatory or traumatic
      events, may suffer from loss of their function. One of the topics arising major
      interest in the research applied to regenerative medicine is represented by
      tissue engineering and, in particular, by stem cells. The study of stem cells in
      dentistry over the years has shown an exponential increase in literature. Adult
      mesenchymal stem cells have recently been isolated and characterized from tooth
      related tissues and they might represent, in the near future, a new gold standard
      in the regeneration of all oral tissues. The aim of our review is to provide an
      overview on the topic reporting the current knowledge for each class of dental
      stem cells and to identify their potential clinical applications as therapeutic
      tool in various branches of dentistry. 

PMID- 25379518
TI  - Comparison of Medpor coated tear drainage tube versus silicon tear drainage tube
      in conjunctivodacryocystorhinostomy: problems and solutions.
AB  - PURPOSE: This study aims at comparing two different types of drainage tubes in
      conjunctivodacryocystorhinostomy, which are used for upper lacrimal system
      obstruction or damage, with respect to their respective postoperative problems
      and solutions. METHODS: Nineteen eyes of 17 patients who underwent
      conjunctivodacryocystorhinostomy (CDCR) or conjunctivorhinostomy (CR) surgery
      with a Medpor coated tear drainage tube or silicon tube placement between
      October, 2010, and February, 2014, were included in this retrospective
      comparative study. RESULTS: In the initial surgery, Medpor coated tear drainage
      tubes were used in 11 eyes by CDCR, whereas silicon tear drainage tubes were
      implanted into 2 eyes by CR and 6 eyes by CDCR. In group 1, proximal and distal
      obstructions developed postoperatively in 4 eyes, while 1 eye showed tube
      malposition and 3 eyes developed luminal obstruction by debris 3 times. In group
      2, tube extrusion developed in 4 eyes, whereas tube malposition developed in 6
      eyes and luminal obstruction by debris developed in 6 eyes at different times,
      for a total of 20 times. CONCLUSIONS: In our study, the most significant
      complication we observed in the use of silicon tear drainage tubes was tube
      extrusion,whereas the leading complication related to the use of Medpor coated
      tear drainage tubes was tube obstruction.

PMID- 25379519
TI  - Bone mineral density at diagnosis of celiac disease and after 1 year of gluten
      free diet.
AB  - Atypical or silent celiac disease may go undiagnosed for many years and can
      frequently lead to loss of bone mineral density, with evolution to osteopenia or
      osteoporosis. The prevalence of the latter conditions, in case of new diagnosis
      of celiac disease, has been evaluated in many studies but, due to the variability
      of epidemiologic data and patient features, the results are contradictory. The
      aim of this study was to evaluate bone mineral density by dual-energy X-ray
      absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per
      protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray
      absorptiometry was repeated after 1 year of gluten-free diet in those with T
      score value <-1 at diagnosis. Stratification of patients according to sex and age
      showed a higher prevalence of low bone mineral density in men older than 30 years
      and in women of all ages. A 1-year gluten-free diet led to a significant
      improvement in lumbar spine and femoral neck mean T-score value. We propose that
      dual-energy X-ray absorptiometry should be performed at diagnosis of celiac
      disease in all women and in male aged >30 years, taking into account each risk
      factor in single patients. 

PMID- 25379521
TI  - Analysis of blocking rate and bandwidth usage of mobile IPTV services in wireless
      cellular networks.
AB  - Mobile IPTV services over wireless cellular networks become more and more
      popular, owing to the significant growth in access bandwidth of wireless cellular
      networks such as 3G/4G and WiMAX. However, the spectrum resources of wireless
      cellular networks is rare. How to enhance the spectral efficiency of mobile
      networks becomes an important issue. Unicast, broadcast, and multicast are the
      most important transport schemes for offering mobile IPTV services over wireless
      cellular networks. Therefore, bandwidth usages and blocking rates of unicast,
      broadcast, and multicast IPTV services were analyzed and compared in this paper.
      Simulations were also conducted to validate the analytical results. Numerical
      results demonstrate that the presented analysis is correct, and multicast scheme
      achieves the best bandwidth usage and blocking rate performance, relative to the
      other two schemes. 

PMID- 25379520
TI  - Antiproliferative effects of methanolic extracts of Cryptocarya concinna Hance
      roots on oral cancer Ca9-22 and CAL 27 cell lines involving apoptosis, ROS
      induction, and mitochondrial depolarization.
AB  - Cryptocarya-derived natural products were reported to have several biological
      effects such as the antiproliferation of some cancers. The possible antioral
      cancer effect of Cryptocarya-derived substances was little addressed as yet. In
      this study, we firstly used the methanolic extracts of C. concinna Hance roots
      (MECCrt) to evaluate its potential function in antioral cancer bioactivity. We
      found that MECCrt significantly reduced cell viability of two oral cancer Ca9-22
      and CAL 27 cell lines in dose-responsive manners (P < 0.01). The percentages of
      sub-G1 phase and annexin V-positive of MECCrt-treated Ca9-22 and CAL 27 cell
      lines significantly accumulated (P < 0.01) in a dose-responsive manner as
      evidenced by flow cytometry. These apoptotic effects were associated with the
      findings that intracellular ROS generation was induced in MECCrt-treated Ca9-22
      and CAL 27 cell lines in dose-responsive and time-dependent manners (P < 0.01).
      In a dose-responsive manner, MECCrt also significantly reduced the mitochondrial
      membrane potential in these two cell lines (P < 0.01-0.05). In conclusion, we
      demonstrated that MECCrt may have antiproliferative potential against oral cancer
      cells involving apoptosis, ROS generation, and mitochondria membrane
      depolarization. 

PMID- 25379522
TI  - Aerobic training modulates the effects of exercise-induced oxidative stress on
      PON1 activity: a preliminary study.
AB  - The aim of the study was to compare the effect of maximal exercise (ME) on
      paraoxonase (PON) and arylesterase (ARE) activity depending on lifestyle in
      respect to physical activity. The study was performed on 46 young men divided
      into two groups: sedentary (S) and physically active (PA). All participants
      performed ME on a treadmill. PON1 activities, FRAP, uric acid, bilirubin, TBARS,
      and lipid profile were determined in their blood before, at the bout of, and
      after ME. No significant differences in PON1 activities were found between S and
      PA subjects at baseline. Nearly all biochemicals increased at ME in both groups.
      Both PON and ARE activity increased at the bout of ME in PA subjects and only ARE
      activity in S subjects. ARE/HDL-C ratio increased at the bout of ME in PA and S
      subjects. The difference in PON1 activity response to ME between study groups may
      be a result of adaptation of PA subjects to regular physical activity. We suggest
      that PON1 activity may be a marker of antioxidant protection at ME and an
      indicator of adaptation to exercise. 

PMID- 25379523
TI  - Bone healing by using Ilizarov external fixation combined with flexible
      intramedullary nailing versus Ilizarov external fixation alone in the repair of
      tibial shaft fractures: experimental study.
AB  - PURPOSE: Our research was aimed at studying the radiographic and histological
      outcomes of using flexible intramedullary nailing (FIN) combined with Ilizarov
      external fixation (IEF) versus Ilizarov external fixation alone on a canine model
      of an open tibial shaft fracture. MATERIALS AND METHODS: Transverse diaphyseal
      tibial fractures were modelled in twenty dogs. Fractures in the dogs of group 1
      (n = 10) were stabilized with the Ilizarov apparatus while it was combined with
      FIN in group 2 (n = 10). RESULTS: On day 14, a bone tissue envelope started
      developing round the FIN wires. Histologically, we revealed only endosteal bone
      union in group 1 while in group 2 the radiographs revealed complete bone union on
      day 28. At the same time-point, the areas of cancellous and mature lamellar bone
      tissues were observed in the intermediary area in group 2. The periosteal layers
      were formed of the trabeculae net of lamellar structure and united the bone
      fragments. The frame was removed at 30 days after the fracture in group 2 and
      after 45 days in group 1 according to bone regeneration. CONCLUSION: The
      combination of the Ilizarov apparatus and FIN accelerates bone repair and
      augments stabilization of tibial shaft fractures as compared with the use of the
      Ilizarov fixation alone.

PMID- 25379524
TI  - Investigation of a new handover approach in LTE and WiMAX.
AB  - Nowadays, one of the most important challenges in heterogeneous networks is the
      connection consistency between the mobile station and the base stations.
      Furthermore, along the roaming process between the mobile station and the base
      station, the system performance degrades significantly due to the interferences
      from neighboring base stations, handovers to inaccurate base station and
      inappropriate technology selection. In this paper, several algorithms are
      proposed to improve mobile station performance and seamless mobility across the
      long-term evolution (LTE) and Worldwide Interoperability for Microwave Access
      (WiMAX) technologies, along with a minimum number of redundant handovers.
      Firstly, the enhanced global positioning system (GPS) and the novel received
      signal strength (RSS) prediction approaches are suggested to predict the target
      base station accurately. Then, the multiple criteria with two thresholds
      algorithm is proposed to prioritize the selection between LTE and WiMAX as the
      target technology. In addition, this study also covers the intercell and
      cochannel interference reduction by adjusting the frequency reuse ratio 3 (FRR3)
      to work with LTE and WiMAX. The obtained results demonstrate high next base
      station prediction efficiency and high accuracy for both horizontal and vertical
      handovers. Moreover, the received signal strength is kept at levels higher than
      the threshold, while maintaining low connection cost and delay within acceptable
      levels. In order to highlight the combination of the proposed algorithms'
      performance, it is compared with the existing RSS and multiple criteria handover
      decision algorithms. 

PMID- 25379525
TI  - Considerations on the use of exogenous fibrolytic enzymes to improve forage
      utilization.
AB  - Digestion of cell wall fractions of forage in the rumen is incomplete due to the
      complex links which limit their degradation. It is therefore necessary to find
      options to optimize the use of forages in ruminant production systems. One
      alternative is to use exogenous enzymes. Exogenous fibrolytic enzymes are of
      fungal or bacterial origin and increase nutrient availability from the cell wall,
      which consists of three fractions in different proportions depending on the
      species of forage: digestible, potentially digestible, and indigestible. The
      response to addition of exogenous enzymes varies with the type of forage; many
      researchers infer that there are enzyme-forage interactions but fail to explain
      the biological mechanism. We hypothesize that the response is related to the
      proportion of the potentially digestible fraction. The exogenous enzyme activity
      depends on several factors but if the general conditions for enzyme action are
      available, the potentially digestible fraction may determine the magnitude of the
      response. Results of experiments with exogenous fibrolytic enzymes in domestic
      ruminants are inconsistent. This, coupled with their high cost, has made their
      use unattractive to farmers. Development of cheaper products exploring other
      microorganisms with fibrolytic activity, such as Fomes fomentarius or
      Cellulomonas flavigena, is required. 

PMID- 25379526
TI  - An investigation on forage yield capacity of kermes oak (Quercus coccifera L.)
      and grazing planning of Mediterranean maquis scrublands for traditional goat
      farming.
AB  - This study investigated grazing capacities of maquis scrubland and preparation
      principles of grazing management in forest resources. Kermes oak (Quercus
      coccifera L.), which is widespread as a main shrub species in maquis vegetation
      in Turkey, and pure hair goats (Capra hircus L.) feeding on shoots and leaves of
      this shrub were selected for study. The study was conducted in two stages. Green
      leaf and shoot samples were taken from kermes oaks in the first stage and the
      amount of green herbage yield (g * m(-1)) and dry matter yield (kg * ha(-1)) that
      may be obtained per unit area from these samples was identified. The considered
      amount of dry matter consumed by pure hair goats daily and the number of goats
      being fed within 1 year on land of 1 ha according to different land coverage
      rates of kermes oaks (goat head * ha * yr) were calculated. In the second stage,
      grazing capacities of sample areas where kermes oak spread were identified and
      compared with the grazing plan prepared by the forestry administration for this
      area. Forage yield variance according to land coverage rates of maquis scrublands
      should be considered when determining optimum animal numbers for grazing per area
      for sustainable goat farming.

PMID- 25379527
TI  - Reporting misconduct of a coworker to protect a patient: a comparison between
      experienced nurses and nursing students.
AB  - PURPOSE: Whistleblowing is the reporting of illegal, immoral, or illegitimate
      practices to persons or organizations that may affect the action. The current
      study compares experienced nurses to nursing students regarding their willingness
      to blow the whistle to protect a patient's interests. METHODS: 165 participants
      were divided into two groups: 82 undergraduate nursing students and 83
      experienced nurses. Participants responded to two vignettes that described a
      colleague's and a manager's misconduct at work. RESULTS: The nursing students
      perceived the severity of the misconduct significantly lower compared to the
      experienced nurses. The nursing students also ranked the internal and external
      whistleblowing indices higher than the nurses, but the differences did not reach
      statistical significance. For each of the examined internal and external indices,
      professional experience was found to be significant in multivariate regression
      analyses. CONCLUSIONS: Even though nursing students perceived the severity of the
      misconduct significantly lower than the experienced nurses, the students
      demonstrated a greater readiness to blow the whistle, both internally and
      externally. Recommendations for handling comparable situations are offered.

PMID- 25379528
TI  - Sex ratio estimations of loggerhead sea turtle hatchlings at Kuriat islands,
      Tunisia: can minor nesting sites contribute to compensate globally female-biased
      sex ratio?
AB  - Hatchling sex ratios in the loggerhead turtle Caretta caretta were estimated by
      placing electronic temperature recorders in seven nests at Kuriat islands
      (Tunisia) during the 2013 nesting season. Based on the mean temperatures during
      the middle third of the incubation period, and on incubation duration, the sex
      ratio of hatchlings at Kuriat islands was highly male-biased. Presently, the
      majority of hatchling sex ratio studies are focused on major nesting areas,
      whereby the sex ratios are universally believed to be heavily female-biased. Here
      we present findings from a minor nesting site in the Mediterranean, where the
      hatchling sex ratio was found to be male-biased, suggesting a potential
      difference between major and minor nesting sites. 

PMID- 25379529
TI  - Response surface methodology: optimisation of antifungal bioemulsifier from novel
      Bacillus thuringiensis.
AB  - An antifungal bioemulsifier compound was produced from a novel strain of Bacillus
      thuringiensis pak2310. To accentuate the production and as the first step to
      improve the yield, a central composite design (CCD) was used to study the effect
      of various factors like minimal salts (1X and 3X), glycerol concentration (2% and
      4%), beef extract concentration (1% and 3%), and sunflower oil concentration (2%
      and 4%) on the production of bioemulsifier molecule and to optimize the
      conditions to increase the production. The E 24 emulsification index was used as
      the response variable as the increase in surfactant production was seen to be
      proportional to increased emulsification. A quadratic equation was employed to
      express the response variable in terms of the independent variables. Statistical
      tools like student's t-test, F-test, and ANOVA were employed to identify the
      important factors and to test the adequacy of the model. Under optimum conditions
      (1X concentration of minimal salts (MS), 2.6% glycerol (v/v), 1% beef extract
      (w/v), and 2% sunflower oil (v/v)) a 65% increase in yield was produced. 

PMID- 25379531
TI  - Estimation of congestion in free disposal hull models using data envelopment
      analysis.
AB  - This paper deals with evaluating congestion in free disposal hull (FDH) models.
      There are several approaches in data envelopment analysis (DEA) literatures which
      discuss the theory and application of congestion. However, almost all of these
      approaches considered convex DEA technologies. So, in the case of nonconvex
      technologies, including FDH technology, this field is almost nil. This paper
      makes an attempt to fill in this void. To do so, this study provides a pairwise
      comparisons-based algorithm to evaluate congestion in FDH model. This algorithm
      identifies the sources of congestion and estimates its amounts. It is also
      capable of detecting the losses amounts of output due to congestion. The validity
      of the proposed model is demonstrated using some numerical and empirical
      examples. 

PMID- 25379530
TI  - Solid tumor-targeting theranostic polymer nanoparticle in nuclear medicinal
      fields.
AB  - Polymer nanoparticles can be prepared by self-assembling of amphiphilic polymers,
      and various types of molecular assemblies have been reported. In particular, in
      medicinal fields, utilization of these polymer nanoparticles as carriers for drug
      delivery system (DDS) has been actively tried, and some nanoparticulate drugs are
      currently under preclinical evaluations. A radionuclide is an unstable nucleus
      and decays with emission of radioactive rays, which can be utilized as a tracer
      in the diagnostic imaging systems of PET and SPECT and also in therapeutic
      purposes. Since polymer nanoparticles can encapsulate most of diagnostic and
      therapeutic agents with a proper design of amphiphilic polymers, they should be
      effective DDS carriers of radionuclides in the nuclear medicinal field. Indeed,
      nanoparticles have been recently attracting much attention as common platform
      carriers for diagnostic and therapeutic drugs and contribute to the development
      of nanotheranostics. In this paper, recent developments of solid tumor-targeting
      polymer nanoparticles in nuclear medicinal fields are reviewed. 

PMID- 25379532
TI  - Cytotoxicity of doxycycline effluent generated by the Fenton process.
AB  - This study aims at determining the Minimum Inhibitory Concentration with
      Escherichia coli ATCC 25922 and cytotoxicity to L929 cells (ATCC CCL-1) of the
      waste generated by doxycycline degradation by the Fenton process. This process
      has shown promise in this treatment thanks mainly to the fact that the waste did
      not show any relevant inhibitory effect on the test organism and no cytotoxicity
      to L-929 cells, thus demonstrating that the antibiotic properties were
      inactivated. 

PMID- 25379533
TI  - Anatomy of the facial nerve at the condylar area: measurement study and clinical
      implications.
AB  - The aim of this study was to elucidate the detailed anatomy of the facial nerve
      (FN) at the condylar area to helping physicians preventing the iatrogenic trauma
      on the nerve. We dissected 25 specimens of the embalmed Korean cadavers (13 males
      and 2 females; mean age 76.9 years). The FN course at the condylar was examined,
      and the location of the FN branches was measured with superficial standards. The
      trunks of the FN emerged in the condylar area as one trunk, two trunks, and a
      loop or plexiform in 36%, 12%, and 52% areas, respectively. The zygomatic branch
      (Zbr) of FN passed over the tragus-alar line 23 mm anterior to the tragus (Tg) in
      most of the cases. The Zbr passed over the vertical line 2 cm anterior to the Tg
      through the area about 6 to 20 mm inferior to the Tg. Regardless of careful
      approach techniques to the condylar area, the FN could be damaged by a careless
      manipulation. Any reference landmarks could not guarantee the safety during the
      approach to the condylar area because more than half of the cases present the
      complicated branching type in the front of the Tg.

PMID- 25379534
TI  - A three-dimensional reconstructive study of pelvic cavity in the New Zealand
      rabbit (Oryctolagus cuniculus).
AB  - The present study has been performed to reveal biometrical aspects and diameter
      related differences in terms of sexes regarding pelvic cavity via three
      dimensional (3D) reconstruction by using multidetector computed tomography (MDCT)
      images of pelvic cavity of the New Zealand rabbit. A total of 16 adult New
      Zealand rabbits, including 8 males and 8 females, were used in this study. Under
      anesthesia, the images obtained from MDCT were stacked and overlaid to
      reconstruct the 3D model of the pelvic cavity using 3D modeling software (Mimics
      13.1). Measurements, such as the conjugate, transverse, and vertical diameters of
      the pelvic cavity, and the pelvic inclination were calculated and analyzed
      statistically. Biometrical differences of the pelvic diameters in New Zealand
      rabbits of both sexes were shown clearly. It was concluded that the pelvic
      diameters revealed by 3D modeling techniques can shed light on medical students
      who take both anatomy training and gynecological applications. The authors hope
      that the synchronization of medical approaches may give rise to novel diagnostic
      and therapeutic developments related to pelvic cavity. 

PMID- 25379536
TI  - Working characteristics of variable intake valve in compressed air engine.
AB  - A new camless compressed air engine is proposed, which can make the compressed
      air energy reasonably distributed. Through analysis of the camless compressed air
      engine, a mathematical model of the working processes was set up. Using the
      software MATLAB/Simulink for simulation, the pressure, temperature, and air mass
      of the cylinder were obtained. In order to verify the accuracy of the
      mathematical model, the experiments were conducted. Moreover, performance
      analysis was introduced to design compressed air engine. Results show that,
      firstly, the simulation results have good consistency with the experimental
      results. Secondly, under different intake pressures, the highest output power is
      obtained when the crank speed reaches 500 rpm, which also provides the maximum
      output torque. Finally, higher energy utilization efficiency can be obtained at
      the lower speed, intake pressure, and valve duration angle. This research can
      refer to the design of the camless valve of compressed air engine.

PMID- 25379535
TI  - Radioimmunotherapy: a specific treatment protocol for cancer by cytotoxic
      radioisotopes conjugated to antibodies.
AB  - Radioimmunotherapy (RIT) represents a selective internal radiation therapy, that
      is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies
      (including those fragments) or peptides. In a clinical field, two successful
      examples of this treatment protocol are currently extended by (90)Y-ibritumomab
      tiuxetan (Zevalin) and (131)I-tositumomab (Bexxar), both of which are anti-CD20
      monoclonal antibodies coupled to cytotoxic radioisotopes and are approved for the
      treatment of non-Hodgkin lymphoma patients. In addition, some beneficial
      observations are obtained in preclinical studies targeting solid tumors. To date,
      in order to reduce the unnecessary exposure and to enhance the therapeutic
      efficacy, various biological, chemical, and treatment procedural improvements
      have been investigated in RIT. This review outlines the fundamentals of RIT and
      current knowledge of the preclinical/clinical trials for cancer treatment. 

PMID- 25379537
TI  - Wide-field fluorescein angiography in wet age-related macular degeneration.
AB  - PURPOSE: The aim of our study was to investigate if peripheral retinal ischaemia
      contributed to the pathogenesis of neovascular AMD (NvAMD), using wide-field
      fluorescein angiography (WFFA). METHODS: This prospective study included 30
      consecutive patients with newly diagnosed NvAMD in the index eye. Wide-field
      colour fundus images and fluorescein angiograms were obtained using P200C optomap
      FA and analysed using a grid with three concentric circles of 50 degrees , 100
      degrees , and 200 degrees  centred on the fovea to define zones Z1, Z2, and Z3.
      RESULTS: Areas of peripheral retinal nonperfusion were seen in 2 (7%) eyes,
      peripheral vascular leakage in 5 (17%) eyes, and diffuse dye leakage close to the
      ora in 5 (17%) eyes. A total of one-third of the study eyes showed changes on
      WFFA in Z2 and Z3. On comparing index eyes to nonindex eyes in these patients,
      the presence of NvAMD was associated with peripheral FA changes (P = 0.009,
      Fisher's test). CONCLUSION: Frank peripheral retinal non-perfusion does not
      appear to be associated with NvAMD. In some patients with active NvAMD there is
      degradation of the peripheral blood-retina barrier. Smoking was also found to be
      associated with the above-mentioned abnormalities.

PMID- 25379538
TI  - Volatile organic silicon compounds in biogases: development of sampling and
      analytical methods for total silicon quantification by ICP-OES.
AB  - Current waste management policies favor biogases (digester gases (DGs) and
      landfill gases (LFGs)) valorization as it becomes a way for energy politics.
      However, volatile organic silicon compounds (VOSiCs) contained into DGs/LFGs
      severely damage combustion engines and endanger the conversion into electricity
      by power plants, resulting in a high purification level requirement. Assessing
      treatment efficiency is still difficult. No consensus has been reached to provide
      a standardized sampling and quantification of VOSiCs into gases because of their
      diversity, their physicochemical properties, and the omnipresence of silicon in
      analytical chains. Usually, samplings are done by adsorption or absorption and
      quantification made by gas chromatography-mass spectrometry (GC-MS) or
      inductively coupled plasma-optical emission spectrometry (ICP-OES). In this
      objective, this paper presents and discusses the optimization of a patented
      method consisting in VOSiCs sampling by absorption of 100% ethanol and
      quantification of total Si by ICP-OES. 

PMID- 25379539
TI  - Contralateral abdominal pocketing in salvation of replanted fingertips with
      compromised circulation.
AB  - Abdominal pocketing is one of the most useful methods in salvation of compromised
      replanted fingertips. Abdominal pocketing has generally been performed in the
      ipsilateral lower abdominal quadrant, but we have also performed contralateral
      pocketing at our institute. To determine which approach is more beneficial, a
      total of 40 patients underwent an abdominal pocketing procedure in either the
      ipsilateral or contralateral lower abdominal quadrant after fingertip
      replantation. Dates of abdominal pocketing after initial replantation, detachment
      after abdominal pocketing, range of motion (ROM) before abdominal pocketing, and
      sequential ROM after the detachment operation and date of full ROM recovery and
      Disabilities of Arm, Shoulder, and Hand questionnaire (DASH) score were recorded
      through medical chart review. Mean detachment date, mean abduction of shoulder
      after the detachment operation, and mean days to return to full ROM were not
      significantly different between the ipsilateral and contralateral pocketing
      groups. However, the mean DASH score was significantly lower in the contralateral
      group than the ipsilateral group. There were also fewer postoperative wound
      complications in the contralateral group than in the ipsilateral group. We,
      therefore, recommend contralateral abdominal pocketing rather than ipsilateral
      abdominal pocketing to increase patient comfort and reduce pain and
      complications. 

PMID- 25379540
TI  - Assessment of serum acylated ghrelin in children and adolescents with chronic
      liver diseases: relation to nutritional status.
AB  - Because ghrelin is one of the key hormones in regulating feeding behavior and
      caloric status, it was suggested that ghrelin behavior might be closely
      associated with malnutrition state of patients with chronic liver disease (CLD).
      Thus, we aimed to assess serum ghrelin levels in children with CLD and its
      relation to anthropometric parameters and severity of CLD. Forty CLD patients
      were studied in comparison to 40 controls. All subjects were subjected to
      history, anthropometric, and laboratory assessment of liver functions and serum
      acylated ghrelin. Ghrelin was higher in patients than controls being higher with
      progress of Child's grade and with deterioration of liver functions.
      Hyperghrelinemia was detected in 62.5% of cases. Ghrelin correlated negatively
      with body mass index standard deviation score (BMISDS (r = -0.95, P < 0.001)),
      triceps skin fold thickness (TSFT (r = -0.88, P < 0.001)), and subscapular skin
      fold thickness (SSFT (r = 0.83, P < 0.001)) percentiles. In conclusion,
      hyperghrelinemia may represent a compensatory mechanism trying to overcome
      malnutrition state complicating CLD and can be used as a parameter for early
      detection and assessment of the severity of malnutrition in children with CLD. 

PMID- 25379541
TI  - Spinal anaesthesia with hyperbaric prilocaine in day-case perianal surgery:
      randomised controlled trial.
AB  - BACKGROUND: The local anaesthetics used in day-case spinal anaesthesia should
      provide short recovery times. We aimed to compare hyperbaric prilocaine and
      bupivacaine in terms of sensory block resolution and time to home readiness in
      day-case spinal anaesthesia. MeTHODS: Fifty patients undergoing perianal surgery
      were randomized into two groups. The bupivacaine-fentanyl group (Group B)
      received 7.5 mg, 0.5% hyperbaric bupivacaine + 20 MUg fentanyl in total 1.9 mL.
      The prilocaine-fentanyl group (Group P) received 30 mg, 0.5% hyperbaric
      prilocaine + 20 MUg fentanyl in the same volume. RESULTS: Time to L1 block and
      maximum block was shorter in Group P than in Group B (Group P 4.6 +/- 1.3 min
      versus Group B 5.9 +/- 01.9 min, P = 0.017, and Group P 13.2 +/- 7.5 min versus
      Group B 15.3 +/- 6.6 min, P = 0.04). The time to L1 regression and S3 regression
      of the sensorial block was significantly shorter in Group P than in Group B (45.7
      +/- 21.9 min versus 59.7 +/- 20.9 min, P = 0.024, and 133.8 +/- 41.4 min versus
      200.4 +/- 64.8 min, P < 0.001). The mean time to home readiness was shorter for
      Group P than for Group B (155 +/- 100.2 min versus 207.2 +/- 62.7 min (P <
      0.001)). CONCLUSION: Day-case spinal anaesthesia with hyperbaric prilocaine +
      fentanyl is superior to hyperbaric bupivacaine in terms of earlier sensory block
      resolution and home readiness and the surgical conditions are comparable for
      perianal surgery.

PMID- 25379542
TI  - Investigation of micro- and nanosized particle erosion in a 90 degrees  pipe bend
      using a two-phase discrete phase model.
AB  - This paper addresses erosion prediction in 3-D, 90 degrees  elbow for two-phase
      (solid and liquid) turbulent flow with low volume fraction of copper. For a range
      of particle sizes from 10 nm to 100 microns and particle volume fractions from
      0.00 to 0.04, the simulations were performed for the velocity range of 5-20 m/s.
      The 3-D governing differential equations were discretized using finite volume
      method. The influences of size and concentration of micro- and nanoparticles,
      shear forces, and turbulence on erosion behavior of fluid flow were studied. The
      model predictions are compared with the earlier studies and a good agreement is
      found. The results indicate that the erosion rate is directly dependent on
      particles' size and volume fraction as well as flow velocity. It has been
      observed that the maximum pressure has direct relationship with the particle
      volume fraction and velocity but has a reverse relationship with the particle
      diameter. It also has been noted that there is a threshold velocity as well as a
      threshold particle size, beyond which significant erosion effects kick in. The
      average friction factor is independent of the particle size and volume fraction
      at a given fluid velocity but increases with the increase of inlet velocities.

PMID- 25379543
TI  - Treatment of medial tibial stress syndrome according to the fascial distortion
      model: a prospective case control study.
AB  - Medial tibial stress syndrome (MTSS) is a common problem among athletes and
      soldiers. There is no proven theory that could explain the pathophysiology of
      shin splints. The therapies described so far are time-consuming and involve a
      high risk of relapse. The method according to the fascial distortion model (FDM)
      addresses local changes in the area of the lower leg fascia. It is suited to
      reduce pain and functional impairments associated with this symptom complex by
      applying targeted manual techniques. 32 patients (male: 30; female: 2)
      participated in this study. Visual analogue scale (VAS) was used for the
      quantification of pain. Scores were also given to rate the maximum painless
      exercise tolerance of the patients. Subsequently treatment of the crural fascia
      was performed. Patients retested ability of running and jumping. Therapy was
      continued until full exercise tolerance or painlessness was reached. A
      significant reduction of the VAS pain score from 5.2 to 1.1 could be achieved (P
      < 0.001). The impairment of exercise tolerance could be reduced from 7 to 2
      points (P < 0.001). The duration of treatment was 6.3 (SD: 4.3) days on average.
      The FDM therapy is a potential effective method for acute treatment of MTSS. 

PMID- 25379544
TI  - Management of intolerance to casting the upper extremities in claustrophobic
      patients.
AB  - INTRODUCTION: Some patients showed unusual responses to the immobilization
      without any objective findings with casts in upper extremities. We hypothesized
      their that intolerance with excessive anxiety to casts is due to claustrophobia
      triggered by cast immobilization. The aim of this study is to analyze the
      relevance of cast immobilization to the feeling of claustrophobia and discover
      how to handle them. METHODS: There were nine patients who showed the
      caustrophobic symptoms with their casts. They were assesed whether they were
      aware of their claustrophobis themselves. Further we investigated the alternative
      immobilization to casts. RESULTS: Seven out of nine cases that were aware of
      their claustrophobic tendencies either were given removable splints initially or
      had the casts converted to removable splints when they exhibited symptoms. The
      two patients who were unaware of their latent claustrophobic tendencies were
      identified when they showed similar claustrophobic symptoms to the previous
      patients soon after short arm cast application. We replaced the casts with
      removable splints. This resolved the issue in all cases. CONCLUSIONS: We should
      be aware of the claustrophobia if patients showed unusual responses to the
      immobilization without any objective findings with casts in upper extremities,
      where removal splint is practical alternative to cast to continue the treatment
      successfully.

PMID- 25379546
TI  - Separation and recovery of fine particles from waste circuit boards using an
      inflatable tapered diameter separation bed.
AB  - Recovering particle materials from discarded printed circuit boards can enhance
      resource recycling and reduce environmental pollution. Efficiently physically
      separating and recovering fine metal particles (-0.5 mm) from the circuit boards
      are a key recycling challenge. To do this, a new type of separator, an inflatable
      tapered diameter separation bed, was developed to study particle motion and
      separation mechanisms in the bed's fluid flow field. For 0.5-0.25 mm circuit
      board particles, metal recovery rates ranged from 87.56 to 94.17%, and separation
      efficiencies ranged from 87.71 to 94.20%. For 0.25-0.125 mm particles, metal
      recovery rates ranged from 84.76 to 91.97%, and separation efficiencies ranged
      from 84.74 to 91.86%. For superfine products (-0.125 mm), metal recovery rates
      ranged from 73.11 to 83.04%, and separation efficiencies ranged from 73.00 to
      83.14%. This research showed that the inflatable tapered diameter separation bed
      achieved efficient particle separation and can be used to recover fine particles
      under a wide range of operational conditions. The bed offers a new mechanical
      technology to recycle valuable materials from discarded printed circuit boards,
      reducing environmental pollution.

PMID- 25379545
TI  - Antimicrobial photodynamic therapy and dental plaque: a systematic review of the
      literature.
AB  - BACKGROUND: The aim of this study was to perform a systematic review of the
      literature on the efficacy of antimicrobial photodynamic therapy (PDTa) on
      cariogenic dental biofilm. TYPES OF STUDIES REVIEWED: Studies in vivo, in vitro,
      and in situ were included. Articles that did not address PDTa, those that did not
      involve cariogenic biofilm, those that used microorganisms in the plankton phase,
      and reviews were excluded. Data extraction and quality assessments were performed
      independently by two raters using a scale. RESULTS: Two hundred forty articles
      were retrieved; only seventeen of them met the eligibility criteria and were
      analyzed in the present review. Considerable variability was found regarding the
      methodologies and application protocols for antimicrobial PDTa. Two articles
      reported unfavorable results. PRACTICAL IMPLICATIONS: The present systematic
      review does not allow drawing any concrete conclusions regarding the efficacy of
      antimicrobial PDTa, although this method seems to be a promising option.

PMID- 25379547
TI  - Validation of a Spanish version of the Lille apathy rating scale for Parkinson's
      disease.
AB  - INTRODUCTION: To date, no rating scales for detecting apathy in Parkinson's
      disease (PD) patients have been validated in Spanish. For this reason, the aim of
      this study was to validate a Spanish version of Lille apathy rating scale (LARS)
      in a cohort of PD patients from Spain. PARTICIPANTS AND METHODS: 130 PD patients
      and 70 healthy controls were recruited to participate in the study. Apathy was
      measured using the Spanish version of LARS and the neuropsychiatric inventory
      (NPI). Reliability (internal consistency, test-retest, and interrater
      reliability) and validity (construct, content, and criterion validity) were
      measured. RESULTS: Interrater reliability was 0.93. Cronbach's alpha for LARS was
      0.81. The test-retest correlation coefficient was 0.97. The correlation between
      LARS and NPI scores was 0.61. The optimal cutoff point under the ROC curve was 
      14, whereas the value derived from healthy controls was -11. The prevalence of
      apathy in our population tested by LARS was 42%. CONCLUSIONS: The Spanish version
      of LARS is a reliable and useful tool for diagnosing apathy in PD patients. Total
      LARS score is influenced by the presence of depression and cognitive impairment.
      However, both disorders are independent identities with respect to apathy. The
      satisfactory reliability and validity of the scale make it an appropriate
      instrument for screening and diagnosing apathy in clinical practice or for
      research purposes.

PMID- 25379548
TI  - Feeding habits and trophic level of the Panama grunt Pomadasys panamensis, an
      important bycatch species from the shrimp trawl fishery in the Gulf of
      California.
AB  - The Panama grunt is an abundant and commercially important species in the
      southeastern Gulf of California, but the research undertaken on this species is
      scarce despite its ecological and economic importance. We studied the feeding
      habits of Panama grunt through stomach content analyses as a first step towards
      understanding the biology of this species in the study area. Our results indicate
      that the Panama grunt is a benthic predator throughout its life cycle and feeds
      mainly on infaunal crustaceans. Diet differences among grunt were not found
      according to size, diet, or season. Shannon diversity index results indicate that
      Panama grunt has a limited trophic niche breadth with a diet dominated by a
      limited number of taxa as crustaceans. The estimated trophic level of this
      species is 3.59. Overall, the Panama grunt is a carnivorous fish occupying the
      intermediate levels of the trophic pyramid. 

PMID- 25379549
TI  - Comprasion of ICare rebound tonometer and Goldmann applanation tonometer in high
      myopia.
AB  - PURPOSE: To compare intraocular pressure (IOP) measurements with the Goldmann
      applanation tonometer (GAT) and the ICare rebound tonometer (RBT) in high myopic
      eyes. PATIENTS AND METHODS: This randomized prospective study included 40 eyes of
      40 patients with high myopia. All patients' central corneal thickness (CCT),
      anterior chamber depth (ACD), axial length (AXL), keratometry, and refractive
      measurements were recorded and followed by IOP measurement with RBT and GAT.
      RESULTS: The average CCT, AXL, and ACD were determined to be 514.65 +/- 32 MUm,
      27.65 +/- 2.22 mm, and 3.25 +/- 0.51 mm, respectively. Mean K was 43.27 +/- 1.4 D
      and mean spherical equivalent was -11.31 +/- 4.30 D. The mean IOP values obtained
      by RBT and GAT were 17.18 +/- 3.72 mmHg and 16.48 +/- 3.19 mmHg, respectively.
      The deviations of RBT readings from corrected GAT values were highly correlated
      with CCT values (r = 0.588, P = 0.0001). The mean corrected GAT reading was 17.49
      +/- 3.01 mmHg. Linear regression analysis showed that a CCT change of 10 MUm
      resulted in an RBT reading deviation of 0.57 mmHg. The Bland-Altman scatter-plot
      and McNemar test showed a clinically good level of agreement between the two
      tonometers. CONCLUSION: This study found a good agreement level between the two
      tonometers in high myopic patients and that RBT measurements are influenced by
      CCT variations.

PMID- 25379551
TI  - Comparison of the level of boron concentrations in black teas with fruit teas
      available on the Polish market.
AB  - The determination of boron by inductively coupled plasma-atomic emission
      spectrometry has been carried in water-soluble and acid soluble (total content)
      fractions of 36 samples of traditional black tea and fruit brew. The estimation
      of the impact of the type of tea on the concentration of boron in water-soluble
      and acid extracts and potential human health risk from the daily intake of boron
      was carried out in this study. The levels of boron differed significantly in
      black and fruit tea types. The mean total content of boron ranged from 8.31 to
      18.40 mg/kg in black teas, from 12.85 to 15.13 mg/kg in black tea with fruit
      flavor, and from 12.09 to 22.77 mg/kg in fruit brews. The degree of extraction of
      boron in black tea ranged from 8% to 27% and for fruit tea from 17% to 69%. In
      addition, the values below 25% were of black teas with fruit flavors. The daily
      intake of B from tea infusions (three cups/day) is still within the average daily
      intake except for some of the fruit brews which exceed acceptable regulations of
      the daily intake of total boron by humans. Hence, it may not produce any health
      risks for human consumption, if other sources of metal contaminated food are not
      taken at the same time.

PMID- 25379550
TI  - Expression of angiogenesis regulatory proteins and epithelial-mesenchymal
      transition factors in platelets of the breast cancer patients.
AB  - Platelets play a role in tumor angiogenesis and growth and are the main
      transporters of several angiogenesis regulators. Here, we aimed to determine the
      levels of angiogenesis regulators and epithelial-mesenchymal transition factors
      sequestered by circulating platelets in breast cancer patients and age-matched
      healthy controls. Platelet pellets (PP) and platelet-poor plasma (PPP) were
      collected by routine protocols. Vascular endothelial growth factor (VEGF),
      platelet-derived growth factor BB (PDGF-BB), thrombospondin-1 (TSP-1), platelet
      factor 4 (PF4), and transforming growth factor-beta1 (TGF-beta1) were measured by
      enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF
      (2.1 pg/10(6) platelets versus 0.9 pg/10(6) platelets, P < 0.001), PF4 (21.2
      ng/10(6) platelets versus 10.2 ng/10(6) platelets, P < 0.001), PDGF-BB (42.9
      pg/10(6) platelets versus 19.1 pg/10(6) platelets, P < 0.001), and TGF-beta1
      (15.3 ng/10(6) platelets versus 4.3 ng/10(6) platelets, P < 0.001) differed in
      the PP samples of cancer and control subjects. In addition, protein
      concentrations were associated with clinical characteristics (P < 0.05).
      Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF
      BB, and TGF-beta1, suggesting a possible target for early diagnosis. VEGF, PDGF,
      and TGF-beta1 concentrations in platelets may be associated with prognosis.

PMID- 25379552
TI  - Safety evaluation of multiple strains of Lactobacillus plantarum and Pediococcus
      pentosaceus in Wistar rats based on the Ames test and a 28-day feeding study.
AB  - Three lactic acid bacterial strains, Lactobacillus plantarum, HK006, and HK109,
      and Pediococcus pentosaceus PP31 exhibit probiotic potential as antiallergy
      agents, both in vitro and in vivo. However, the safety of these new strains
      requires evaluation when isolated from infant faeces or pickled cabbage. Multiple
      strains (HK006, HK109, and PP31) were subject to a bacterial reverse mutation
      assay and a short-term oral toxicity study. The powder product exhibited
      mutagenic potential in Salmonella Typhimurium strains TA98 and TA1535 (with or
      without metabolic activation). In the short-term oral toxicity study, rats
      received a normal dosage of 390 mg/kg/d (approximately 9 * 10(9) CFU/kg/d) or a
      high dosage of 1950 mg/kg/d (approximately 4.5 * 10(10) CFU/kg/d) for 28 d. No
      adverse effects were observed regarding the general condition, behaviour, growth,
      feed and water consumption, haematology, clinical chemistry indices, organ
      weights, or histopathologic analysis of the rats. These studies have demonstrated
      that the consumption of multiple bacterial strains is not associated with any
      signs of mutagenicity of S. Typhimurium or toxicity in Wistar rats, even after
      consuming large quantities of bacteria.

PMID- 25379553
TI  - Development of strand-specific real-time RT-PCR to distinguish viral RNAs during
      Newcastle disease virus infection.
AB  - Newcastle disease virus (NDV) causes large losses in the global fowl industry. To
      better understand NDV replication and transcription cycle, quantitative detection
      methods for distinguishing NDV genomic RNA (gRNA), antigenomic RNA (cRNA), and
      messenger RNA (mRNA) in NDV-infected cells are indispensible. Three reverse
      transcription primers were designed to specifically target the nucleoprotein (NP)
      region of gRNA, cRNA, and NP mRNA, and a corresponding real-time RT-PCR assay was
      developed to simultaneously quantify the three types of RNAs in NDV-infected
      cells. This method showed very good specificity, sensitivity, and
      reproducibility. The detection range of the assay was between 5.5 * 10(2) and 1.1
      * 10(9) copies/MUL of the target gene. These methods were applied to investigate
      the dynamics of the gRNA, cRNA, and mRNA synthesis in NDV La Sota infected DF-1
      cells. The results showed that the copy numbers of viral gRNA, cRNA, and NP mRNA
      all exponentially increased in the beginning. The viral RNA copy number then
      plateaued at 10'h postinfection and gradually decreased from 16 h postinfection.
      No synthesis priority was observed between replication (gRNA and cRNA amounts)
      and transcription (mRNA amounts) during NDV infection. However, the cRNA
      accumulated more rapidly than gRNA, as the cRNA copy number was three- to tenfold
      higher than gRNA starting from 2 h postinfection. Conclusion. A real-time RT-PCR
      for absolute quantitation of specific viral RNA fragments in NDV-infected cells
      was developed for the first time. The development of this assay will be helpful
      for further studies on the pathogenesis and control strategies of NDV.

PMID- 25379554
TI  - Overweight and obesity epidemic in developing countries: a problem with diet,
      physical activity, or socioeconomic status?
AB  - Obesity is a significant public health concern affecting more than half a billion
      people worldwide. Obesity rise is not only limited to developed countries, but to
      developing nations as well. This paper aims to compare the mean body mass index
      trends in the World Health Organisation- (WHO-) categorised regions since 1980 to
      2008 and secondly to appraise how socioeconomic disparities can lead to
      differences in obesity and physical activity level across developing nations.
      Taking into account past and current BMI trends, it is anticipated that obesity
      will continue to take a significant ascent, as observed by the sharp increase
      from 1999 to 2008. Gender differences in BMI will continue to be as apparent,
      that is, women showing a higher BMI trend than men. In the coming years, the
      maximum mean BMI in more developed countries might be exceeded by those in less
      developed ones. Rather than focusing on obesity at the individual level, the
      immediate environment of the obese individual to broader socioeconomic contexts
      should be targeted. Most importantly, incentives at several organisational
      levels, the media, and educational institutions along with changes in food
      policies will need to be provided to low-income populations. 

PMID- 25379555
TI  - Influence of conventional and ultrasonic-assisted extraction on phenolic
      contents, betacyanin contents, and antioxidant capacity of red dragon fruit
      (Hylocereus polyrhizus).
AB  - The aim of this study was to examine the effects of extraction methods on
      antioxidant capacities of red dragon fruit peel and flesh. Antioxidant capacities
      were measured using ethylenebenzothiozoline-6-sulfonic acid (ABTS) radical cation
      assay and ferric reducing antioxidant power assay (FRAP). Total phenolic content
      (TPC) was determined using Folin-Ciocalteu reagent while quantitative
      determination of total flavonoid content (TFC) was conducted using aluminium
      trichloride colorimetric method. Betacyanin content (BC) was measured by
      spectrophotometer. Red dragon fruit was extracted using conventional (CV) and
      ultrasonic-assisted extraction (UE) technique to determine the most efficient way
      of extracting its antioxidant components. Results indicated that UE increased
      TFC, reduced the extraction yield, BC, and TPC, but exhibited the strongest
      scavenging activity for the peel of red dragon fruit. In contrast, UE reduced BC,
      TFC, and scavenging activity but increased the yield for the flesh. Nonetheless,
      UE slightly increases TPC in flesh. Scavenging activity and reducing power were
      highly correlated with phenolic and flavonoid compounds. Conversely, the
      scavenging activity and reducing power were weakly correlated with betacyanin
      content. This work gives scientific evidences for the consideration of the type
      of extraction techniques for the peel and flesh of red dragon fruit in applied
      research and food industry. 

PMID- 25379556
TI  - Utility of Preoperative CA125 Assay in the Management Planning of Women Diagnosed
      with Uterine Cancer.
AB  - Objective. This study assesses the role of preoperative serum CA125 levels in the
      planning treatment options for women diagnosed with uterine cancer. Material and
      Method. Ninety five consecutive patients diagnosed with uterine cancer during a
      four-year period were identified. Age ranged from 35 to 89 years with a mean age
      of 69 years. The preoperative CA125 levels were dichotomised at 28 U/mL (using
      ROC analysis to identify the best discriminating threshold for 5-year survival).
      This level was then correlated with preoperative prognostic indicators: patient
      age, tumour grade, and histopathological tumour cell type. Survival data was
      plotted using Kaplan-Meier curves and analysed using the log-rank test.
      Univariate and multivariate analysis were performed to identify the predictors of
      overall survival. Results. The mean age of patients was 69 years (range: 35-89).
      On univariate analysis, the use of preoperative CA125 levels of greater or less
      than 28 U/mL correlated significantly with age (P = 0.01), the grade of disease
      (P = 0.02) and unfavourable tissue type (P = 0.03). This threshold CA125 level
      had a sensitivity of 75%, specificity of 76%, positive predictive value of 35%
      and negative predicative value of 96.25%, and a likelihood ratio of 3.12 for
      predicting nodal disease. Using a threshold of preoperative CA125 level of 28
      U/mL (area under curve: 0.60) was also a significant predictor of 5-year survival
      (log-rank test, P = 0.01). Using Cox multivariate survival analysis to identify
      predictive preoperative factors overall, unfavourable cell type was the strongest
      predictor of survival (Chi square = 36.5, df = 4, and P = 0.001), followed by
      preoperative CA125 level (CA125 > 28 U/mL, P = 0.011) and unfavourable
      preoperative grade (P = 0.017). Amongst patients with a favourable histological
      tissue type (endometrioid), preoperative CA125 levels predicted overall survival
      (Chi square = 6.039, df = 2, P = 0.02); however unfavourable preoperative grade
      did not (P = 0.5). Overall, at five-year follow-up, while there were no deaths
      among the women with preoperative serum CA125 less than 12 U/mL, eleven of the
      twenty-three deaths (47.82%) in the study occurred in women with a preoperative
      CA125 more than 28 U/mL. Conclusions. A preoperative CA125 assay for women with
      uterine cancer is a relatively inexpensive, reproducible, and objective test
      which provides valuable information regarding the risk of metastatic disease and
      overall likelihood of long term survival. Patients with a low likelihood of
      metastatic/nodal disease (favourable tissue type and CA125 level < 28 U/mL) and
      significant comorbidities may benefit from avoiding an extended complete staging
      procedure. Alternatively, a high level of CA125 may prompt further imaging and
      multidisciplinary discussions to plan for individualised management and
      consideration for recruitment to clinical trials. 

PMID- 25379557
TI  - Treatment of sternoclavicular joint osteomyelitis with debridement and delayed
      resection with muscle flap coverage improves outcomes.
AB  - The objective of this study was to evaluate the efficacy of various treatment
      options for sternoclavicular joint osteomyelitis. We evaluated patients with a
      diagnosis of sternoclavicular joint osteomyelitis, treated at our hospital from
      2002 to 2012. Four treatment options were compared. Three out of twelve patients
      were successfully cured with antibiotics alone (25%). Debridement with or without
      negative pressure therapy was successful for one of three patients (33%).
      Simultaneous debridement, bone resection, and muscle flap coverage of the
      acquired defect successfully treated one of two patients (50%). Debridement with
      delayed bone resection and muscle flap coverage was successful in five of five
      patients (100%). Osteomyelitis of the sternoclavicular joint is a rare disease
      that has become more prevalent in recent years and can be associated with
      increasing use of long-term indwelling catheters. Initial debridement with
      delayed bone resection and pectoralis major muscle flap coverage can effectively
      treat sternoclavicular joint osteomyelitis. 

PMID- 25379558
TI  - Alterations in the Coagulation System during Major Visceral Surgery in Children.
AB  - Purpose. The description of the alterations in the hemostatic system in children
      undergoing abdominal surgery is sparse. Enhanced clinical outcomes for previously
      untreatable conditions have led to an increased incidence of venous
      thromboembolic complications. Alterations in children's coagulation system during
      major abdominal operations compared to minor procedures were examined. Methods.
      Children (0-12 years) undergoing either laparotomy, thoracotomy, or minor surgery
      were included. Participants were divided into two groups: group 1 was open
      laparotomy including operations for solid abdominal tumours and thoracotomy,
      while group 2 was minor surgery. Activated partial thromboplastin time (aPTT), D
      dimer, INR, and fibrinogen were measured. Results. Both groups had a shorter
      aPTT, higher INR, and lower fibrinogen concentrations after the operation, while
      D-dimer was unaltered. The changes were, however, discrete and probably not
      clinically significant. On day 3, all parameters except aPTT in group 1 (not
      measured in group 2) indicated a continuous coagulation activity. Conclusion. The
      tendency for coagulation activity altered based on the length and degree of
      surgery. A continuously altered activity was observed compatible with the
      reported increased risk of venous thromboembolism at day 3. However, before
      introducing thromboprophylaxis guidelines larger series of multicentre studies
      are needed. 

PMID- 25379559
TI  - A Surgeon's Perspective of Abdominal Wall Endometriosis at a Caesarean Section
      Incision: Nine Cases in a Single Institution.
AB  - Abdominal wall endometriosis in a Caesarean section scar (AEC) is an infrequent
      type of extrapelvic endometriosis which rarely transforms into a malignant
      lesion. A painful mass located in the scar of a Caesarean section is a typical
      sign of AEC. This condition is diagnosed preoperatively using imaging modalities
      such as computed tomography and ultrasonography, as well as fine-needle
      aspiration. Although AEC has typical signs, general surgeons often misdiagnose it
      due to its rarity. Herein, we report our experience of AEC in a single
      institution. 

PMID- 25379560
TI  - Flow cytometric evaluation of T cell activation markers after cardiopulmonary
      bypass.
AB  - Background. Cardiopulmonary bypass surgery (CPBS) is associated with an increased
      risk for infections or with subsequent organ dysfunction. As T cell activation is
      a central mechanism during inflammatory processes, we developed an assay to
      evaluate T cell activation pathways in patients undergoing CPBS. Methods. Blood
      was obtained from eleven patients undergoing CPBS preoperatively, on
      postoperative day (POD)-3, and on POD-7 and was stimulated with different
      concentrations of Concanavalin A (ConA). Cyclosporine and sirolimus, inhibiting
      different pathways of the T cell cycle, were added to blood ex vivo. Expression
      of T cell activation markers CD25 and CD95 was analyzed by flow cytometry.
      Results. In untreated blood, expression of CD25 and CD95 significantly increased
      with higher ConA concentrations (P < 0.05) and decreased for all ConA
      concentrations for both antigens over the study time (P < 0.05). Independently
      from the ConA concentration, inhibition of CD25 and CD95 expression was highest
      preoperatively for sirolimus and on POD-3 for cyclosporine. At all time points,
      inhibition of CD25 and CD95 expression was significantly higher after
      cyclosporine compared to sirolimus treatment (P < 0.001). Conclusion. Our results
      showed that different pathways of T cell activation are impaired after CPBS. Such
      knowledge may offer the opportunity to identify patients at risk for
      postoperative complications. 

PMID- 25379562
TI  - Awareness and attitude of healthcare workers to cosmetic surgery in osogbo,
      Nigeria.
AB  - This study aimed at understanding the level of awareness and elucidates the
      attitude and disposition of healthcare workers to cosmetic surgery in Osogbo,
      Nigeria. A questionnaire-based survey was done at LAUTECH Teaching Hospital,
      Osogbo, in 2012. Questionnaires were administered to 213 workers and students in
      the hospital. These were then analysed using SPSS version 16.0 with frequencies,
      means, and so forth. Respondents were 33 doctors, 32 nurses, 79 medical students,
      60 nursing students, 4 administrative staff, 1 pharmacist, and 4 ward maids.
      There is fair awareness about cosmetic surgery generally with 94.5% and its
      availability in Nigeria with 67.0%. A fewer proportion of the respondents (44.5%)
      were aware of the facility for cosmetic surgery in their locality. A large
      percentage (86.5%) favorably considers facilities outside Nigeria when making
      choice of facility to have cosmetic surgery done. 85.5% considered the
      information about cosmetic surgery reliable while 19.0% objected going for
      cosmetic surgery of their choice even if done free. Only 34.0% consider cosmetic
      surgery socially acceptable. Although the awareness of health workers about
      cosmetic surgery is high, their disposition to it is low. There is a need to
      increase the awareness in order to increase cosmetic surgery practice in Nigeria.

PMID- 25379561
TI  - Percutaneous vertebral body augmentation: an updated review.
AB  - There are many medical conditions like osteoporosis, tumor, or osteonecrosis that
      weaken the structural strength of the vertebral body and prone it to fracture.
      Percutaneous vertebral augmentation that is usually applied by
      polymethylmethacrylate is a relatively safe, effective, and long lasting
      procedure commonly performed in these situations. In this paper, we updated a
      review of biomechanics, indications, contraindications, surgical techniques,
      complications, and overall prognosis of these minimally invasive spinal
      procedures. 

PMID- 25379563
TI  - Pre- and postoperative vomiting in children undergoing video-assisted gastrostomy
      tube placement.
AB  - Background. The aim of this study was to determine the incidence of pre- and
      postoperative vomiting in children undergoing a Video-Assisted Gastrostomy (VAG)
      operation. Patients and Methods. 180 children underwent a VAG operation and were
      subdivided into groups based on their underlying diagnosis. An anamnesis with
      respect to vomiting was taken from each of the children's parents before the
      operation. After the VAG operation, all patients were followed prospectively at
      one and six months after surgery. All complications including vomiting were
      documented according to a standardized protocol. Results. Vomiting occurred
      preoperatively in 51 children (28%). One month after surgery the incidence was 43
      (24%) in the same group of children and six months after it was found in 40
      (22%). There was a difference in vomiting frequency both pre- and postoperatively
      between the children in the groups with different diagnoses included in the
      study. No difference was noted in pre- and postoperative vomiting frequency
      within each specific diagnosis group. Conclusion. The preoperative vomiting
      symptoms persisted after the VAG operation. Neurologically impaired children had
      a higher incidence of vomiting than patients with other diagnoses, a well-known
      fact, probably due to their underlying diagnosis and not the VAG operation. This
      information is useful in preoperative counselling. 

PMID- 25379564
TI  - Autologous fat transfer: an aesthetic and functional refinement for
      parotidectomy.
AB  - Parotidectomy is a surgical procedure associated to functional (Frey's syndrome)
      as well as aesthetic (facial asymmetry) complications that can be very disturbing
      for the patient. Several procedures have been described to primarily avoid or
      secondarily reconstruct the facial defect and treat the neurological iatrogenic
      syndrome. Autologous fat transfer was primarily used in 10 cases to avoid such
      complications. It is an easy technique widely used in cosmetic and reconstructive
      surgery. This technique gives very satisfying long-term results on the cosmetic
      as well as on the physiological point of view. 

PMID- 25379565
TI  - An Intra-Abdominal Pseudocyst around a Ventriculoperitoneal Shunt due to
      Streptococcus Infection 7 Years after Shunt Surgery.
AB  - In 1999, a 50-year-old woman underwent ventriculoperitoneal (VP) shunt surgery
      for hydrocephalus after subarachnoid hemorrhage. She was hospitalized for fever
      and recurrent systemic seizures in November 2006. Head computed tomography (CT)
      showed only old changes. The seizures and fever were controlled by medicinal
      therapy. However, in December, her consciousness level suddenly decreased, and
      she showed progressive lower abdominal distension. Head CT showed marked
      ventriculomegaly, and abdominal CT showed a giant cystic mass at the shunt-tube
      tip in the lower abdominal cavity. Because thick pus was aspirated from the intra
      abdominal mass, we diagnosed the patient with acute obstructive hydrocephalus due
      to an infected abdominal pseudocyst. Laparotomy and direct cyst drainage were
      performed, and antibiotic therapy against Streptococcus, the causative pathogen,
      was administered. The VP shunt tube was replaced. The postoperative course was
      uneventful, and postoperative CT showed hydrocephalus improvement and no
      pseudocyst recurrence. Abdominal pseudocysts, which are rare after VP shunt
      surgeries, usually occur after the subacute postoperative course in younger
      cerebral hemorrhagic cases. Our case was quite rare because the cyst developed in
      the chronic phase in an older patient and was caused by streptococcal infection.
      The cyst components should be examined before cyst drainage when choosing
      surgical strategies. 

PMID- 25379566
TI  - Laparoscopic cholecystectomy performed by residents: a retrospective study on 569
      patients.
AB  - Introduction. Aim of this study was to evaluate the safety of laparoscopic
      cholecystectomy performed by residents. Materials and Methods. We retrospectively
      reviewed 569 elective laparoscopic cholecystectomies. Results. Duration of
      surgery was 84 +/- 39 min for residents versus  66 +/- 47 min for staff surgeons,
      P < 0.001. Rate of conversion was 3.2% for residents versus 2.7% for staff
      surgeons, P = 0.7. There was no difference in the rates of intraoperative and
      postoperative complications for residents (1.2% and 3.2%) versus staff surgeons
      (1.5% and 3.1%), P = 0.7 and P = 0.9. Postoperative hospital stay was 3.3 +/- 1.8
      days for residents versus  3.4 +/- 3.2 days for staff surgeons, P = 0.6. One
      death in patients operated by residents (1/246) and one in patients operated by
      staff surgeons (1/323) were found, P = 0.8. No difference in the time to return
      to normal daily activities between residents (11.3 +/- 4.2 days) and staff
      surgeons (10.8 +/- 5.6 days) was found, P = 0.2. Shorter duration of surgery when
      operating the senior residents (75 +/- 31 minutes) than the junior residents (87
      +/- 27 minutes), P = 0.003. Conclusion. Laparoscopic cholecystectomy performed by
      residents is a safe procedure with results comparable to those of staff surgeons.

PMID- 25379567
TI  - Skin staples: a safe technique for securing mesh in lichtensteins hernioplasty as
      compared to suture.
AB  - Background. Lichtenstein tension free repair is the most commonly used technique
      due to cost effectiveness, low recurrence rate, and better patient satisfaction.
      This study was done to compare the duration of surgery and postoperative outcome
      of securing mesh with skin staples versus polypropylene sutures in Lichtenstein
      hernia repair. Materials and Methods. A total of 96 patients with inguinal hernia
      undergoing Lichtenstein mesh repair were randomly assigned into two groups. The
      mesh was secured either by using skin staples (group I) or polypropylene sutures
      (group II). Results. The operation time was significantly reduced from mesh
      insertion to completion of skin closure in group I (mean 20.7 min) as compared to
      group II (mean 32.7 min) with significant P value (P < 0.0001) and less
      complication rate in group I as compared to group II. Conclusion. Mesh fixation
      with skin staples is as effective as conventional sutures with added advantage of
      significant reduction in the operating time and complications or recurrence. The
      staples can be applied much more quickly than sutures for fixing the mesh, thus
      saving the operating time. Infection rate is significantly decreased with
      staples. 

PMID- 25379568
TI  - VorinostatSAHA Promotes Hyper-Radiosensitivity in Wild Type p53 Human
      Glioblastoma Cells.
AB  - Glioblastoma multiforme (GBM) is a very aggressive and locally invasive tumor.
      The current standard of care is partial brain radiation therapy (60 Gy)
      concurrently with the alkylating agent temozolomide (TMZ). However, patients'
      survival remains poor (6-12 months) mainly due to local and diffuse (distant)
      recurrence. The possibility to promote hyper radiosensitivity (HRS) with low dose
      radiation may contribute to improve outcome. Here, we evaluated the effect of
      VorinostatSAHA and TMZ on glioblastoma cells' sensitivity to low dose radiation.
      Clonogenic survivals were performed on D54 (p53 and PTEN wild type) and U118 (p53
      and PTEN mutants) cells exposed to clinically relevant doses of VorinostatSAHA
      and TMZ and increasing radiation doses. Apoptosis was measured by the activation
      of caspase-3 and the role of p53 and PTEN were evaluated with the p53 inhibitor
      pifithrin alpha and the PI3K/AKT pathway inhibitor LY29002. VorinostatSAHA
      promoted HRS at doses as low as 0.25 Gy in the D54 but not the U118 cells.
      Killing efficiency was associated with caspase-3 activation, delayed H2AX
      phosphorylation and abrogation of a radiation -induced G2 arrest. Inhibiting p53
      function with pifithrin alpha prevented the promotion of HRS by VorinostatSAHA.
      Moreover, LY29002, a PI-3K inhibitor, restored promotion of HRS by VorinostatSAHA
      in the p53 mutant U118 cells to levels similar to the p53 wild type cells. TMZ
      also promoted HRS at doses as low as 0.15 Gy. These finding indicate that HRS can
      be promoted in p53 wild type glioblastoma cells through a functional PTEN to
      delay DNA repair and sensitize cells to low dose radiation. Promotion of HRS thus
      appears to be a viable approach for GBM that could be used as a basis to develop
      new Phase I/II studies.

PMID- 25379569
TI  - Possible computational filter to detect proteins associated to influenza A
      subtype H1N1.
AB  - The design of drugs with bioinformatics methods to identify proteins and peptides
      with a specific toxic action is increasingly recurrent. Here, we identify toxic
      proteins towards the influenza A virus subtype H1N1 located at the UniProt
      database. Our quantitative structure-activity relationship (QSAR) approach is
      based on the analysis of the linear peptide sequence with the so-called Polarity
      Index Method that shows an efficiency of 90% for proteins from the Uniprot
      Database. This method was exhaustively verified with the APD2, CPPsite, Uniprot,
      and AmyPDB databases as well as with the set of antibacterial peptides studied by
      del Rio et al. and Oldfield et al. 

PMID- 25379570
TI  - Evaluation of the effects of antibiotics on cytotoxicity of EGFP and DsRed2
      fluorescent proteins used for stable cell labeling.
AB  - The use of fluorescent markers has proven to be an attractive tool in biological
      imaging. However, its usefulness may be confined by the cytotoxicity of the
      fluorescent proteins. In this article, for the first time, we have examined an
      influence of the antibiotics present in culture medium on cytotoxicity of the
      EGFP and DsRed2 markers used for whole-cell labeling. Results showed that
      doxycycline negatively affected albumin synthesis in DsRed2-expressing hepatoma
      cells, and that both hepatoma cells and human skin fibroblasts, labeled with this
      protein, were characterized by the lowered growth rates. Thus, the cytotoxic
      effect of fluorescent markers depends on both protein used for cell labeling and
      on growth conditions that may cause cell stress. 

PMID- 25379571
TI  - "V-junction": a novel structure for high-speed generation of bespoke droplet
      flows.
AB  - We present the use of microfluidic "V-junctions" as a droplet generation strategy
      that incorporates enhanced performance characteristics when compared to more
      traditional "T-junction" formats. This includes the ability to generate target
      sized droplets from the very first one, efficient switching between multiple
      input samples, the production of a wide range of droplet sizes (and size
      gradients) and the facile generation of droplets with residence time gradients.
      Additionally, the use of V-junction droplet generators enables the suspension and
      subsequent resumption of droplet flows at times defined by the user. The high
      degree of operational flexibility allows a wide range of droplet sizes, payloads,
      spacings and generation frequencies to be obtained, which in turn provides for an
      enhanced design space for droplet-based experimentation. We show that the V
      junction retains the simplicity of operation associated with T-junction formats,
      whilst offering functionalities normally associated with droplet-on-demand
      technologies. 

PMID- 25379572
TI  - Influence of moisture on the preparation, crystal structure, and photophysical
      properties of organohalide perovskites.
AB  - The effect of preparing lead-based organohalide perovskites under inert
      conditions has been investigated. We find that when prepared under anhydrous
      conditions, only poorly crystalline powders were obtained. On exposure to small
      amounts of moisture a rapid crystallization into the expected cubic unit cell for
      CH3NH3PbBr3 and tetragonal cell for CH3NH3PbI3 is observed. While the as-prepared
      iodide phase is non-emissive, the lifetime of the emission for the bromide is
      found to be much longer when prepared under atmospheric conditions. 

PMID- 25379573
TI  - G-spot: the facts to the fantasy.

PMID- 25379574
TI  - Need to evaluate empirical evidence before formulating theory.

PMID- 25379575
TI  - Causation or association: running before we can walk?

PMID- 25379576
TI  - Obesity substantially impacts low-risk pregnancies.

PMID- 25379577
TI  - Time to stop offering prophylactic chemotherapy after molar  pregnancies?

PMID- 25379578
TI  - Information provision for screening programmes requires a complex,   person
      centred approach.

PMID- 25379580
TI  - Behind the scenes.

PMID- 25379579
TI  - Male breast cancer: a rare disease  that might uncover underlying  pathways of
      breast cancer.
AB  - There are similarities between breast cancers that arise in men and women but
      there are also differences. What can be learned from male breast cancer to gain
      insight into breast cancer pathogenesis?

PMID- 25379581
TI  - Business intelligence analytics.

PMID- 25379582
TI  - Proceedings of the 6th International Veterinary Vaccines and Diagnostic
      Conference, July 29-Aug 2, 2012, Cairns, Australia.

PMID- 25379583
TI  - 2013 IEEE Scientific Visualization Contest winner: Observing genomics and
      phenotypical patterns in the developing mouse brain.

PMID- 25379584
TI  - Virtual reality for the masses.

PMID- 25379586
TI  - The eventual triumph of art.

PMID- 25379585
TI  - [Local hemostasis control by using of oxidized cellulose drugs].

PMID- 25379587
TI  - Proceedings of the 6th Computational Structural Bioinformatics Workshop, October
      4, 2012, Philadelphia, Pennsylvania.

PMID- 25379588
TI  - [Professor A. V. Martynov and his school].

PMID- 25379589
TI  - Special Issue in Honor of Marc Jeannerod.

PMID- 25379591
TI  - Reflections: neurology and the humanities. Aging doctors.

PMID- 25379590
TI  - Proceedings and abstracts of the 52nd Annual Congress of the German Nuclear
      Medicine Society, March 26-29, 2014, Hanover, Germany.

PMID- 25379592
TI  - Author response.

PMID- 25379593
TI  - Development and optimization of a non-enzymatic method of leukocyte isolation
      from macaque tissues.
AB  - BACKGROUND AND METHODS: Cell isolation from macaque tissues involves laborious
      enzymatic digestion. The Medimachine provides a simpler, quicker non-enzymatic
      method, yielding 1.5-5 million cells/g of vaginal or rectal tissue from pigtailed
      macaques. RESULTS AND CONCLUSIONS: Flow cytometry analysis of the two methods
      revealed similar levels of cell viability and most major cell lineage and
      activation markers.

PMID- 25379594
TI  - Pharmacokinetic evaluation of tenofovir disoproxil fumarate released from an
      intravaginal ring in pigtailed macaques after 6 months of continuous use.
AB  - BACKGROUND AND METHODS: A reservoir intravaginal ring (IVR) eluting tenofovir
      disoproxil fumarate (TDF) was evaluated for 6 months of continuous use in
      normally cycling female pigtailed macaques with monthly IVR exchanges to define
      pharmacokinetics and safety. RESULTS AND CONCLUSIONS: Tenofovir levels in vaginal
      secretions and tissue remained consistent for 6 months with no adverse safety
      concerns.

PMID- 25379596
TI  - MERS-CoV update: what you need to know.

PMID- 25379595
TI  - Preclinical evaluation of the immunomodulatory lymphocyte trafficking drug FTY720
      for HIV prevention in the female genital mucosa of macaques.
AB  - FTY720 has been shown to reduce inflammatory cytokines and immune cells in the
      genital mucosa of macaques. This pilot study examined the ability of FTY720 to
      inhibit HIV acquisition. Systemic treatment with FTY720 failed to prevent or
      delay vaginal SHIV transmission.

PMID- 25379597
TI  - Highlights from the 54th ICAAC.

PMID- 25379598
TI  - Are knee biomechanics different in those with and without patellofemoral
      osteoarthritis after anterior cruciate ligament reconstruction?
AB  - OBJECTIVE: Patellofemoral (PF) osteoarthritis (OA) is prevalent following
      anterior cruciate ligament reconstruction (ACLR). This study aimed to investigate
      differences in transverse plane rotation between knees with varus and valgus
      alignment during gait in people with and without PFOA after ACLR. METHODS: Thirty
      six individuals who were mean +/- SD 9 +/- 2 years post-ACLR (18 radiographic
      PFOA and 18 no knee OA) participated in this cross-sectional study. Knee internal
      external rotation angles were measured using a 3-dimensional motion analysis
      system during walking and running. Weight-bearing frontal plane knee alignment,
      measured with an inclinometer, was used to classify participants as having varus
      or valgus alignment. Two-way analysis of covariance was used to assess the effect
      of both PFOA and frontal plane knee alignment on dynamic knee internal-external
      rotation. RESULTS: Significant interactions were found between PFOA status and
      frontal plane alignment on knee internal-external rotation angles during walking
      (P = 0.019) and running (P = 0.002). Tests of simple effects revealed that during
      walking, individuals with valgus alignment and PFOA demonstrated a mean 3.9
      degrees  (95% confidence interval [95% CI] 0.7, 7.1) less knee internal rotation
      than those with valgus alignment and no OA. During running this difference
      increased to 6.1 degrees  (95% CI 1.8, 10.4). For individuals with varus
      alignment, no significant effects were observed. CONCLUSION: Less knee internal
      rotation during gait was found in individuals with PFOA and valgus alignment. A
      rotational shift of this magnitude may be sufficient to initiate or accelerate
      patellofemoral cartilage degeneration. Prospective studies are required to
      determine if these altered kinematic patterns result from, or contribute to, PFOA
      development after reconstruction.

PMID- 25379599
TI  - Hematoidin.

PMID- 25379600
TI  - Diffuse large B-cell lymphoma in leukemic  phase.

PMID- 25379601
TI  - Food for thought: the complex and  controversial interaction between diet  and
      physical activity.

PMID- 25379602
TI  - Diagnosis and management of urinary tract infections in the emergency department.
AB  - Urinary tract infections are a heterogeneous group of disorders, involving
      infection of all or part of the urinary tract, and are defined by bacteria in the
      urine with clinical symptoms that may be acute or chronic. Approximately 1
      million urinary tract infections are treated every year in United States
      emergency departments. The female-to-male ratio is 6:1. Urinary tract infections
      are categorized as upper versus lower tract involvement and as uncomplicated
      versus complicated. The emergency clinician must carefully categorize the
      infection and take into account patient host factors to optimally treat and
      disposition patients. A working knowledge of local or at least national
      susceptibility patterns of the most likely pathogens is essential. A variety of
      special populations exist that require special management, including pregnant
      females, patients with anatomic abnormalities, and instrumented patients.

PMID- 25379603
TI  - Molecular characteristics of humic acids isolated from vermicomposts and their
      relationship to bioactivity.
AB  - Vermitechnology is an effective composting method, which transforms biomass into
      nutrient-rich organic fertilizer. Mature vermicompost is a renewable organic
      product containing humic substances with high biological activity. The aim of
      this study was to assess the chemical characteristics and the bioactivity of
      humic acids isolated from different vermicomposts produced with either cattle
      manure, sugar cane bagasse, sunflower cake from seed oil extraction, or filter
      cake from a sugar cane factory. More than 200 different molecules were found, and
      it was possible to identify chemical markers on humic acids according to the
      nature of the organic source. The large hydrophobic character of humic extracts
      and the preservation of altered lignin derivatives confer to humic acids the
      ability to induce lateral root emergence in maize seedlings. Humic acid-like
      substances extracted from plant biomass residues represent an additional valuable
      product of vermicomposting that can be used as a plant growth promoter. 

PMID- 25379604
TI  - Transcranial direct current stimulation and cognitive training in the
      rehabilitation of Alzheimer disease: A case study.
AB  - In the present study we tested the cognitive effects of transcranial direct
      current stimulation (tDCS) in a case of probable Alzheimer disease (AD). The
      patient (male, 60 years, mild AD) underwent two cycles of treatments, separated
      by 2 months. In the first cycle, active stimulation (10 sessions, 2 mA for 20
      min; anode over the left dorsolateral prefrontal cortex) was followed by
      computerised tasks (CTs) specifically chosen to engage the most impaired
      cognitive processes in the patient (tDCS+CT condition). In the second cycle,
      which was structured as the first, CTs were administered after placebo
      stimulation (sham+CT condition). Effects on cognitive performance were evaluated
      not only by the CTs, but also by neuropsychological tests assessing global
      cognitive functioning. Statistical analyses revealed that whereas the tDCS+CT
      condition had few effects on the CTs, it induced a stability of the patient's
      global cognitive functioning lasting approximately 3 months, which was not
      achieved when the patient underwent sham+CT condition. Therefore, the synergetic
      use of tDCS and CTs appeared to slow down the cognitive decline of our patient.
      This preliminary result, although in need of further confirmation, suggests the
      potentiality of tDCS as an adjuvant tool for cognitive rehabilitation in AD.

PMID- 25379605
TI  - Carbon and chlorine isotope analysis to identify abiotic degradation pathways of
      1,1,1-trichloroethane.
AB  - This study investigates dual C-Cl isotope fractionation during 1,1,1-TCA
      transformation by heat-activated persulfate (PS), hydrolysis/dehydrohalogenation
      (HY/DH) and Fe(0). Compound-specific chlorine isotope analysis of 1,1,1-TCA was
      performed for the first time, and transformation-associated isotope fractionation
      epsilon bulk C and epsilon bulk Cl values were -4.0 +/- 0.20/00 and no chlorine
      isotope fractionation with PS, -1.6 +/- 0.20/00 and -4.7 +/- 0.10/00 for HY/DH, 
      7.8 +/- 0.40/00 and -5.2 +/- 0.20/00 with Fe(0). Distinctly different dual
      isotope slopes (Deltadelta13C/Deltadelta37Cl): infinity with PS, 0.33 +/- 0.04
      for HY/DH and 1.5 +/- 0.1 with Fe(0) highlight the potential of this approach to
      identify abiotic degradation pathways of 1,1,1-TCA in the field. The trend
      observed with PS agreed with a C-H bond oxidation mechanism in the first reaction
      step. For HY/DH and Fe(0) pathways, different slopes were obtained although both
      pathways involve cleavage of a C-Cl bond in their initial reaction step. In
      contrast to the expected larger primary carbon isotope effects relative to
      chlorine for C-Cl bond cleavage, epsilon bulk C < epsilon bulk Cl was observed
      for HY/DH and in a similar range for reduction by Fe(0), suggesting the
      contribution of secondary chlorine isotope effects. Therefore, different
      magnitude of secondary chlorine isotope effects could at least be partly
      responsible for the distinct slopes between HY/DH and Fe(0) pathways. Following
      this dual isotope approach, abiotic transformation processes can unambiguously be
      identified and quantified.

PMID- 25379607
TI  - Structure and molecular characterization of barley nudix hydrolase genes.
AB  - Putative nudix hydrolase (NUDX) genes, which encode amino acid sequences showing
      homology with those of Arabidopsis NUDXs and conserve nudix motif, were
      identified from barley. The 14 deduced barley NUDXs (HvNUDX1-14) were classified
      into established subfamilies, except for 8-oxo-deoxyguanosine 5'-triphosphate (8
      oxo-dGTP) pyrophosphohydrolase and mRNA decapping enzyme subfamilies, and three
      substrate-unknown subfamilies. Drought and UV-C stresses, respectively, up
      regulated 7 and 4 HvNUDX genes, but some homologs of Arabidopsis NUDXs showed
      different responses to abiotic stress. HvNUDX12 gene, belonging to diadenosine
      tetraphosphates (Ap4A) pyrophosphohydrolase subfamily gene and up-regulated by UV
      C, was expressed in Escherichia coli cells. The recombinant protein showed 8-oxo
      dGTP, Ap4A, and guanosine-3',5'-tetraphosphate (ppGpp) pyrophosphohydrolase
      activities, and the suppression of the lacZ amber mutation in a mutT-deficient E.
      coli cells caused by the incorporation of 8-oxo-GTP into mRNA was prevented to a
      significant degree. These results suggest that barley NUDXs have unique
      constitution and response of NUDX to abiotic stress.

PMID- 25379608
TI  - Landauer limit of energy dissipation in a magnetostrictive particle.
AB  - According to Landauer's principle, a minimum amount of energy proportional to
      temperature must be dissipated during the erasure of a classical bit of
      information compensating the entropy loss, thereby linking the information and
      thermodynamics. Here, we show that the Landauer limit of energy dissipation is
      achievable in a shape-anisotropic single-domain magnetostrictive nanomagnet
      having two mutually anti-parallel degenerate magnetization states that store a
      bit of information. We model the magnetization dynamics using the stochastic
      Landau-Lifshitz-Gilbert equation in the presence of thermal fluctuations and show
      that on average the Landauer bound is satisfied, i.e. it is in accordance with
      the generalized Landauer's principle for small systems with stochastic
      fluctuations. 

PMID- 25379606
TI  - Reactivity and chemoselectivity of allenes in Rh(I)-catalyzed intermolecular (5 +
      2) cycloadditions with vinylcyclopropanes: allene-mediated rhodacycle formation
      can poison Rh(I)-catalyzed cycloadditions.
AB  - Allenes are important 2pi building blocks in organic synthesis and engage as 2
      carbon components in many metal-catalyzed reactions. Wender and co-workers
      discovered that methyl substituents on the terminal allene double bond
      counterintuitively change the reactivities of allenes in [Rh(CO)2Cl]2-catalyzed
      intermolecular (5 + 2) cycloadditions with vinylcyclopropanes (VCPs). More
      sterically encumbered allenes afford higher cycloadduct yields, and such effects
      are also observed in other Rh(I)-catalyzed intermolecular cycloadditions. Through
      density functional theory calculations (B3LYP and M06) and experiment, we
      explored this enigmatic reactivity and selectivity of allenes in [Rh(CO)2Cl]2
      catalyzed intermolecular (5 + 2) cycloadditions with VCPs. The apparent low
      reactivity of terminally unsubstituted allenes is associated with a competing
      allene dimerization that irreversibly sequesters rhodium. With terminally
      substituted allenes, steric repulsion between the terminal substituents
      significantly increases the barrier of allene dimerization while the barrier of
      the (5 + 2) cycloaddition is not affected, and thus the cycloaddition prevails.
      Computation has also revealed the origin of chemoselectivity in (5 + 2)
      cycloadditions with allene-ynes. Although simple allene and acetylene have
      similar reaction barriers, intermolecular (5 + 2) cycloadditions of allene-ynes
      occur exclusively at the terminal allene double bond. The terminal double bond is
      more reactive due to the enhanced d-pi* backdonation. At the same time, insertion
      of the internal double bond of an allene-yne has a higher barrier as it would
      break pi conjugation. Substituted alkynes are more difficult to insert compared
      with acetylene, because of the steric repulsion from the additional substituents.
      This leads to the greater reactivity of the allene double bond relative to the
      alkynyl group in allene-ynes. 

PMID- 25379609
TI  - SAR studies on tetrahydroisoquinoline derivatives: the role of flexibility and
      bioisosterism to raise potency and selectivity toward P-glycoprotein.
AB  - The development of P-glycoprotein (P-gp) ligands remains of considerable
      interest, mostly for investigating the protein's structure and transport
      mechanism. In recent years, many different generations of ligands have been
      tested for their ability to modulate P-gp activity. The aim of the present work
      is to perform SAR studies on tetrahydroisoquinoline derivatives in order to
      design potent and selective P-gp ligands. For this purpose, the effect of
      bioisosteric replacement and the role of flexibility have been investigated, and
      four series of tetrahydroisoquinoline ligands have been developed: (a) 2
      aryloxazole bioisosteres, (b) elongated analogues, (c) 2H-chromene, and (d) 2
      biphenyl derivatives. The results showed that both 2-biphenyl derivative 20b and
      elongated derivative 6g behaved as strong P-gp substrates. In conclusion,
      important aspects for developing potent and selective P-gp ligands have been
      highlighted, providing a solid starting point for further optimization. 

PMID- 25379610
TI  - Downregulation of LRPPRC induces apoptosis in prostate cancer cells through the
      mitochondria-mediated pathway.
AB  - Leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) is a
      multifunctional protein involved in the mitochondrial gene expression and
      function, cell cycle progression, and tumorigenesis. However, the functional role
      of LRPPRC in prostate cancer (PCa) has not yet been elucidated. In this study,
      two PCa cell lines were examined to determine the effects of LRPPRC on cell
      proliferation, invasion, and apoptosis in vitro. Our results showed that the
      expression levels of LRPPRC were significantly decreased in the two PCa cell
      lines after transfection with small interfering RNA (siRNA)-LRPPRC. Knockdown of
      LRPPRC by siRNA significantly inhibited the invasion and promoted the apoptosis
      of PCa cells. In addition, downregulation of LRPPRC expression resulted in the
      reduced expression of Bcl-2, upregulation of Bax, and cleaved caspase-9 and
      caspase-3. Taken together, these results show that the downregulation of LRPRPC
      expression induces apoptosis through the mitochondria-mediated pathway in PCa
      cells. These experimental data seem to suggest that LRPPRC plays a critical role
      in the development of PCa, and its inhibition could present a potential molecular
      approach for the treatment of PCa.

PMID- 25379611
TI  - Op18/stathmin is involved in the resistance of taxol among different epithelial
      carcinoma cell lines.
AB  - PURPOSE: Taxol is an effective chemotherapeutic agent against epithelial-derived
      carcinomas, and resistance of carcinoma cells to taxol has developed with the
      wide prescription of the drug. In this study, five different epithelial carcinoma
      cell lines were randomly employed to screen the resistant cell line to taxol, and
      to explore the probable mechanism of taxol-resistant development. MATERIALS AND
      METHODS: Cells were grouped into the controls and the taxol treated. The
      treatment effects of five different epithelial carcinoma cell lines, including
      CNE1, Hep3B-2, MGC, MCF-7, and NCI-H1299, after being treated by taxol were
      analyzed through inspecting the ratios of cellular apoptosis, inhibition of
      cellular proliferation, the capability of cell colony formation and wound
      recovery, and the interference of cell motility and invasion, while western blot
      analysis and siRNA targeting Op18/stathmin were applied to explore the probable
      mechanism on the taxol resistance difference in these cells. RESULTS: Nonsmall
      cell lung cancer NCI-H1299 cells presented obvious taxol resistance, and the
      inhibition of cell motility and invasion was also the weakest in taxol-treated
      NCI-H1299 cells among these five cell lines. Microtubule dynamics analysis
      demonstrated that taxol treatment destroyed normal microtubule arrays and caused
      obvious microtubule collapse in CNE1, Hep3B-2, MGC, and MCF-7 rather than NCI
      H1299, while the latter expressed high levels of microtubule-destabilizing
      protein Op18/stathmin. Inhibition of Op18/stathmin expression increased the
      sensitivity to taxol and promoted cellular apoptosis in NCI-H1299 cells.
      CONCLUSION: NCI-H1299 cells are evidently resistant to taxol-induced cellular
      apoptosis, inhibition of cellular proliferation and wound recovery, as well as
      cell migration and invasion interference, which are closely associated with the
      changes of microtubule dynamics. High expression of Op18/stathmin is perhaps a
      crucial determinant of taxol-resistant development in NCI-H1299 cells.

PMID- 25379612
TI  - Improved kit formulation for preparation of (99m)Tc-HYNIC-TOC: results of
      preliminary clinical evaluation in imaging patients with neuroendocrine tumors.
AB  - (99m)Tc-HYNIC-TOC is a cost-effective and logistically viable agent for
      scintigraphy of neuroendocrine tumors overexpressing somatostatin receptors as
      compared with [(111)In-DTPA-D-Phe(1)] Octreotide (Octreoscan((r))). Several
      studies have been reported, wherein the efficacy of this agent is demonstrated.
      In the present article, the authors report the preparation of a single-vial HYNIC
      TOC kit suitable for the preparation of 4-5 patient doses (15 mCi/patient) of
      (99m)Tc-HYNIC-TOC. The kits were tested for sterility and bacterial endotoxins to
      assure safety of the product. A significant modification in this kit is the
      inclusion of buffer in the kit itself, unlike in commercially available kits
      where the buffer solution has to be added during preparation. (99m)Tc-HYNIC-TOC
      was prepared by adding 20-80 mCi (740-2960 MBq) of freshly eluted Na(99m)TcO4 in
      1-3 mL of sterile saline directly into the kit vial and heating the vial in a
      water bath at 100 degrees C for 20 minutes. The labeling yield and radiochemical
      purity of (99m)Tc-HYNIC-TOC, prepared using the lyophilized cold kit, were
      consistently >90%. The kits were evaluated over a period of 9 months and found to
      be stable when stored at -20 degrees C. Limited clinical studies performed with
      the (99m)Tc-HYNIC-TOC, formulated using the kit, showed adequate sensitivity and
      specificity for the detection of gasteroenteropancreatic neuroendocrine tumors.

PMID- 25379613
TI  - Biological effects of irradiating hepatocellular carcinoma cells by internal
      exposure with 125I-labeled 5-iodo-2'-deoxyuridine-chitosan drug loading
      nanoparticles.
AB  - In this study, the authors evaluate the biological effects of irradiation of
      hepatocellular carcinoma cells by internal exposure with (125)I-labeled 5-iodo-2'
      deoxyuridine ((125)I-UdR)-chitosan drug loading nanoparticles ((125)I-UdR-CS
      DLN). The authors observed that accumulation of nanoparticles was significantly
      (p<0.05) higher in hepatocellular carcinoma cells HepG2 than normal liver cells
      HL-7702 after treated with (125)I-UdR-CS-DLN for 30 minutes. Survival of HepG2
      cells was significantly lower at (125)I-UdR-CS-DLN doses higher than 37 kBq/mL
      (more significant in the G1 phase and G2/M phase) than the HL-7702 cells. In
      addition, (125)I-UdR-CS-DLN induced a higher level of DNA double-strand breaks
      than (125)I-UdR, and HepG2 cells exhibited a lower level of DNA repair when
      compared with HL-7702 cells. In vivo animal experiments, TUNEL staining, after
      targeted treatment, showed that (125)I-UdR-CS-DLN induced significant cell
      apoptosis in rabbit hepatocellular tumors in situ than (125)I-UdR infusion at the
      same dose. In conclusion, hepatocellular carcinoma cells were significantly
      irradiated with (125)I-UdR-CS-DLN compared with (125)I-UdR, and (125)I-UdR-CS-DLN
      irradiation enhanced DNA damage, induced liver cancer cell apoptosis, and
      prevented DNA damage repair. However, evaluating the extent of damage and organ
      sparing in vivo should also be considered.

PMID- 25379614
TI  - Diversity-oriented approach to CF3CHF-, CF3CFBr-, CF3CF2-, (CF3)2CH-, and
      CF3(SCF3)CH-substituted arenes from 1-(diazo-2,2,2-trifluoroethyl)arenes.
AB  - Arenes substituted with perfluoroalkyl groups are attractive targets for drug and
      agrochemical development. Exploiting the carbenic character of donor/acceptor
      diazo compounds, a diversity-oriented synthesis of perfluoroalkylated arenes, for
      late stage fluorofunctionalization, is described. The reaction of 1-(diazo-2,2,2
      trifluoroethyl)arenes with HF, F/Br, F2, CF3H, and CF3SH sources give direct
      access to a variety of perfluoroalkyl-substituted arenes presenting with
      incremental fluorine content. The value of this approach is also demonstrated for
      radiochemistry and positron emission tomography with the [(18)F]-labeling of
      CF3CHF-, CF3CBrF-, and CF3CF2-arenes from [(18)F]fluoride. 

PMID- 25379615
TI  - Enhanced performance of methamphetamine lateral flow cassettes using an
      electronic lateral flow reader.
AB  - Surface contamination from methamphetamine in meth labs continues to be a
      problem. We had previously developed a lateral flow assay cassette for field
      detection of methamphetamine contamination that is commercially available and has
      been used by a number of groups to assess contamination. This cassette uses the
      complete disappearance of the test line as an end point for detection of 50
      ng/100 cm2 of methamphetamine contamination for surface sampling with cotton
      swabs. In the present study, we further evaluate the response of the cassettes
      using an electronic lateral flow reader to measure the intensities of the test
      and control lines. The cassettes were capable of detecting 0.25 ng/ml for
      calibration solutions. For 100 cm2 ceramic tiles that were spiked with
      methamphetamine and wiped with cotton-tipped wooden swabs wetted in
      assay/sampling buffer, 1 ng/tile was detected using the reader. Semi-quantitative
      results can be produced over the range 0-10 ng/ml for calibration solutions and 0
      25 ng/tile for spiked tiles using either a 4-parameter logistic fit of test line
      intensity versus concentration or spiked mass or the ratio of the control line to
      the test line intensity fit to concentration or spiked mass. Recovery from the
      tiles was determined to be about 30% using the fitted curves. Comparison of the
      control line to the test line was also examined as a possible visual detection
      end point and it was found that the control line became more intense than the
      test line at 0.5 to 1 ng/ml for calibration solutions or 1 to 2 ng/tile for
      spiked tiles. Thus the lateral flow cassettes for methamphetamine have the
      potential to produce more sensitive semi-quantitative results if an electronic
      lateral flow reader is used and can be more sensitive for detection if the
      comparison of the control line to the test line is used as the visual end point.

PMID- 25379616
TI  - High vapor pressure deficit drives salt-stress-induced rice yield losses in
      India.
AB  - Flooded rice is grown across wide geographic boundaries from as far north as
      Manchuria and as far south as Uruguay and New South Wales, primarily because of
      its adaptability across diverse agronomic and climatic conditions. Salt-stress
      damage, a common occurrence in delta and coastal rice production zones, could be
      heightened by the interactions between high temperature and relative humidity
      (vapor pressure deficit--VPD). Using temporal and spatial observations spanning
      107 seasons and 19 rice-growing locations throughout India with varying
      electrical conductivity (EC), including coastal saline, inland saline, and
      alkaline soils, we quantified the proportion of VPD inducing salinity damage in
      rice. While controlling for time-invariant factors such as trial locations, rice
      cultivars, and soil types, our regression analysis indicates that EC has a
      nonlinear detrimental effect on paddy rice yield. Our estimates suggest these
      yield reductions become larger at higher VPD. A one standard deviation (SD)
      increase in EC from its mean value is associated with 1.68% and 4.13% yield
      reductions at median and maximum observed VPD levels, respectively. Yield
      reductions increase roughly sixfold when the one SD increase is taken from the
      75th percentile of EC. In combination, high EC and VPD generate near catastrophic
      crop loss as predicted yield approaches zero. If higher VPD levels driven by
      global warming materialize in conjunction with rising sea levels or salinity
      incursion in groundwater, this interaction becomes an important and necessary
      predictor of expected yield losses and global food security.

PMID- 25379617
TI  - Faggot-like cells observed in acute myeloid leukemia with myelodysplasia-related
      changes mimicking acute promyelocytic leukemia.

PMID- 25379618
TI  - Tumor suppressors in follicular lymphoma.
AB  - Follicular lymphoma (FL) is the most common indolent lymphoma. The vast majority
      of cases are associated with the chromosome translocation t(14;18), a somatic
      rearrangement that leads to constitutive expression of the anti-apoptotic BCL2
      protein. Although t(14;18) clearly represents an important early event in FL
      pathogenesis, abundant evidence indicates that it is not sufficient. In
      particular, the recent application of next-generation DNA sequencing technology
      has uncovered numerous recurrent somatic genomic alterations associated with FL,
      most of which affect tumor suppressor genes (TSGs). In this article we review the
      existing literature on TSGs involved in the development and progression of FL. We
      consider the genes that are most frequently targeted by deleterious mutation,
      deletion or epigenetic silencing, along with strategies for developing new
      treatments that exploit the susceptibilities that may be conferred on lymphoma
      cells by the loss of particular TSGs. 

PMID- 25379619
TI  - Patients with Philadelphia-positive leukemia with Y253H or F359V mutation have a
      high risk of developing new mutations in the setting of dasatinib resistance.
AB  - The treatment outcome and development of new mutations in patients with imatinib-
      and/or nilotinib-failure Philadelphia chromosome positive (Ph+) leukemia with
      highly nilotinib-resistant mutations (Y253H, E255K/V and F359V/C) were assessed
      on dasatinib therapy. A total of 111 patients with Ph+ leukemia were grouped into
      three cohorts by baseline BCR-ABL kinase domain mutation status: no mutation (n =
      44), non-nilotinib-resistant mutations (n = 26) or nilotinib-resistant mutations
      (n = 41). The frequencies of hematological, cytogenetic and molecular responses
      and clinical resistance to dasatinib were similar among the three cohorts during
      dasatinib therapy. In dasatinib-resistant patients, new mutations were most
      frequently observed in the cohort with nilotinib-resistant mutations (p = 0.001).
      Multivariate analysis revealed that advanced disease and harboring Y253H or F359V
      mutation before dasatinib were independent predictors of developing new
      mutations. We conclude that patients with Ph+ leukemia with Y253H or F359V
      mutation have a high likelihood of developing new mutations in the setting of
      dasatinib resistance. 

PMID- 25379620
TI  - Clonal Epstein-Barr virus-positive mucocutaneous ulcer mimicking a mature B-cell
      lymphoma in a patient with mycophenolate-induced immune suppression.

PMID- 25379621
TI  - Cell of origin predicts outcome to treatment with etoposide-containing
      chemotherapy in young patients with high-risk diffuse large B-cell lymphoma.
AB  - Addition of etoposide to the R-CHOP chemotherapy regimen with cyclophosphamide,
      doxorubicin, vincristine, prednisone and rituximab (R-CHOEP) has resulted in
      improved survival in young patients with high-risk diffuse large B-cell lymphoma
      (DLBCL). It is not known whether biological factors can predict this effect. In
      this study, 245 patients representing all young patients with high-risk DLBCL
      treated with R-CHOP or R-CHOEP in 2004-2012 in Denmark were extracted from the
      Danish lymphoma database. Patients were stratified according to cell of origin
      (COO) into germinal-center B-cell-like (GCB) or non-GCB by Hans' algorithm. Only
      in patients with the GCB phenotype was treatment with R-CHOEP associated with
      improved progression-free survival (PFS) and overall survival (OS) compared with
      R-CHOP. Patients with GCB phenotype treated with R-CHOEP also had superior OS
      compared with patients with non-GCB phenotype treated with R-CHOEP. This was not
      seen in R-CHOP treated patients. This could suggest that R-CHOEP should be
      restricted to patients with GCB phenotype. 

PMID- 25379622
TI  - Treatment of catheter-related deep vein thrombosis in patients with acute
      leukemia with anticoagulation.
AB  - Patients with acute leukemia develop venous thrombosis (VT) related to central
      venous catheters (CVCs). Anticoagulation (AC) in these patients who are
      thrombocytopenic and often coagulopathic is challenging. To evaluate the safety
      and efficacy of AC in treating CVC-related VT, we retrospectively compared
      outcomes of patients with acute leukemia who were treated or not with AC during
      induction chemotherapy and post-discharge. Twenty-one patients with CVC-related
      VT received AC, 14 did not. VT resolved in 80% of patients in the AC group
      (similarly with low-dose and high-dose enoxaparin) and 45% in the non-AC group (p
      = 0.11). Fourteen (67%) patients in the AC group are alive (median survival not
      reached), compared to four patients (29%) in the non-AC group (median survival 9
      months) (p = 0.015) with a hazard ratio (HR) of 0.32 (95% confidence interval:
      0.12-0.85) in favor of AC. HR remained < 1 after adjustments for leukemia type
      and cytogenetics. Bleeding (< grade 4) occurred in five and one patients in the
      AC vs. non-AC groups, respectively (p = 0.37). 

PMID- 25379623
TI  - Association of foods enriched in conjugated linoleic acid (CLA) and CLA
      supplements with lipid profile in human studies: a systematic review and meta
      analysis.
AB  - OBJECTIVE: The present study aimed to review the association of conjugated
      linoleic acid (CLA) consumption in two forms, foods enriched in CLA and CLA
      supplements, with serum lipid profile in human studies. DESIGN: Systematic review
      and meta-analysis. SETTING: Search process was conducted in PubMed, Cochrane
      Library, Google Scholar, Scopus and Science Direct. Clinical trials that
      investigated the association of CLA intakes either in the form of supplements or
      enriched foods with lipid profile in healthy adults were included. All outcomes
      were recorded as continuous variables, and the effect size was measured by
      analysis of the mean and standard deviation before and after the intervention for
      case and control groups. SUBJECTS: Healthy adult population. RESULTS: CLA
      supplementation was associated with a significant decrease in LDL cholesterol
      (mean difference = -0.218; 95% CI -0.358, -0.077; P = 0.002), a non-significant
      decrease in HDL cholesterol (mean difference = -0.051; 95% CI -0.188, 0.086; P =
      0.468), a non-significant increase in total cholesterol (mean difference = 0.009;
      95% CI -0.128, 0.146; P = 0.896) and a non-significant decrease in TAG (mean
      difference = -0.065; 95% CI -0.20, 0.07; P = 0.344). Foods enriched with CLA were
      associated with significantly decreased LDL cholesterol (mean difference = 
      0.231; 95% CI -0.438, -0.024; P = 0.028), non-significantly increased HDL-C (mean
      difference = 0.075; 95% CI -0.121, 0.270; P=0.455), non-significantly decreased
      total cholesterol (mean difference = -0.158; 95% CI -0.349, 0.042; P = 0.124) and
      non-significantly decreased TAG (mean difference = -0.078; 95% CI -0.274, 0.117;
      P = 0.433). CONCLUSIONS: According to our analysis, consumption of foods enriched
      with CLA or CLA supplements has favourable effects on LDL cholesterol levels.

PMID- 25379624
TI  - Texting teens in transition: the use of text messages in clinical intervention
      research.
AB  - BACKGROUND: The rapidly growing population of young adults living with congenital
      heart disease (CHD), currently challenging ill-prepared cardiac care systems,
      presents a novel population in which to consider the use of mHealth. This
      methodological study was part of a larger study that tested the effectiveness of
      a clinic-based nursing intervention to prepare teens for transfer from pediatric
      to adult cardiology care. The intervention included creation of a MyHealth
      Passport and subsequently SMS (short message service) text messages between the
      intervention nurse and study participant. OBJECTIVE: Our aim was to determine (1)
      the preference of teens with CHD to be contacted via text message following the
      nursing intervention, (2) the effectiveness of texting to collect data regarding
      the use of MyHealth Passport after participation in the intervention, (3) the
      nature of the texting interaction, and (4) the risks and benefits of texting.
      METHODS: Participants were recruited through the intervention study (n=24) by
      either choosing to receive information from the study coordinator through text
      message, or texting a question to the study nurses. Inclusion criteria were age
      15-17 years, diagnosed with moderate or complex heart disease, and currently
      being followed by the Division of Cardiology at Stollery Children's Hospital.
      Exclusion criteria were heart transplantation and/or less than a 6th grade
      reading and comprehension ability. Text message transcripts were analyzed by
      qualitative inductive content analysis. RESULTS: Two-thirds of teens (16/24, 67%)
      chose text messaging as their preferred contact, making them eligible for the
      study. Texting was effective in collecting information regarding the MyHealth
      Passport; all but one teen had their MyHealth Passport on them, and many reported
      carrying it with them wherever they went. All teens reported showing their
      MyHealth Passport to at least one person. Seven themes were identified in the
      texting transcripts: mixing formal and informal language, the passive teen,
      interaction with health care providers, texting teens in transition, texting as a
      mechanism to initiate other forms of communication, affirmation, and the nurse as
      an educator. Benefits of texting were identified as flexibility, ability to
      respond over time, information presented in byte-sized amounts, and information
      directly related to patient questions. Risks of texting were identified as the
      possibility that interactions may not be in-depth, distraction of teen and
      researcher, and invasiveness. CONCLUSIONS: Text messaging was useful in
      collecting data regarding the use of the MyHealth Passport. Text messaging
      resulted in conversations with the teens that were sometimes in-depth and
      meaningful, especially when combined with other communication modalities. Using
      text messaging in a manner resulting in full conversations with the patients
      requires more study and may benefit from protocols and the use of solid
      theoretical foundations that would standardize the interaction so that more
      conclusions could be drawn.

PMID- 25379625
TI  - Characteristics and health perceptions of complementary and alternative medicine
      users in the United States.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) use has been increasing
      and these unconventional therapies do have important adverse effects. We
      evaluated predictors of CAM use among U.S. adults. METHODS: We analyzed the 2007
      Health Information National Trends Survey (n=7503) and used logistic regression
      models to evaluate the association of demographic, lifestyle characteristics and
      healthcare perceptions of respondents who used CAM within the previous 12 months
      (n=1980) versus those who did not (n=5523). We used survey weights in all
      analyses and performed variance estimations using Taylor series linearization to
      account for the complex survey design. RESULTS: Females (odds ratio [OR]=1.46;
      95% confidence interval [CI]: 1.15-1.86), college graduates (OR=1.61; 95% CI:
      1.24-2.08) and those who considered the quality of their healthcare to be poor
      (OR=2.16; 95% CI: 1.28-3.65) were more likely to use CAM, whereas blacks
      (OR=0.58; 95% CI: 0.39-0.85) were less likely to use CAM. Among CAM users, 47.6%
      did not inform their doctors. However, no factor predicted those who did not
      inform their doctors of their CAM use. CONCLUSIONS: Many adults in the United
      States use CAM without informing their doctors. Care providers should inquire
      about CAM usage from their patients, document them and counsel their patients
      regarding their use of these less regulated therapies.

PMID- 25379626
TI  - Coronary artery aneurysms associated with ascending aortic aneurysms and
      abdominal aortic aneurysms: pathophysiologic implications.
AB  - BACKGROUND: Coronary artery aneurysms (CAA) are seen in 1-5% of angiograms.
      Aneurysmal coronary disease has been thought to be a variant of atherosclerotic
      coronary artery disease (CAD) in most patients, but this has not been
      systematically studied. METHODS: To better understand the pathophysiology of CAA,
      we reviewed the cardiac catheterization films of 403 patients with ascending
      thoracic aortic aneurysms and 74 patients with abdominal aortic aneurysms (AAA)
      who underwent surgery for their aortic aneurysms at our institution. Coronary
      aneurysms had diameters 1.5-fold that of a reference segment. RESULTS: The
      incidences of CAA in patients with ascending aneurysms and AAA were 17% and 16%
      respectively (P = 0.92). CAAs in the ascending group were larger (mean diameter
      5.9 vs. 5.0 mm, P = 0.12) with larger reference vessel size (3.1 vs. 2.6 mm, P =
      0.03). CAAs in the patients with ascending aneurysms were less likely to be CAD
      associated within the same vessel (12% vs. 75%, P < 0.001). This difference
      remained significant after controlling for the presence of generalized CAD. No
      other differences in CAAs between the two groups were found. Within the ascending
      aneurysm group, the only clinical variable independently associated with CAA was
      bicuspid aortic valve (OR 0.47, 95% confidence interval 0.25-0.89, P = 0.02). The
      majority of patients with CAA in the ascending aortic aneurysm population did not
      have CAD or any other previously identified cause of CAA. CONCLUSIONS: There is a
      high incidence of CAA in patients with aortic aneurysms. In patients with
      ascending aortic aneurysms there is likely a mechanism distinct from CAD that
      causes CAAs.

PMID- 25379627
TI  - Caregiver perceptions of children who have complex communication needs following
      a home-based intervention using augmentative and alternative communication in
      rural Kenya: an intervention note.
AB  - A high level of unmet communication need exists amongst children with
      developmental disabilities in sub-Saharan Africa. This study investigated
      preliminary evidence of the impact associated with a home-based, caregiver
      implemented intervention employing AAC methods, with nine children in rural Kenya
      who have complex communication needs. The intervention used mainly locally
      sourced low-tech materials, and was designed to make use of the child's strengths
      and the caregiver's natural expertise. A pretest-posttest design was used in the
      study. Data were gathered using an adapted version of the Communication Profile,
      which was based on the International Classification of Functioning, Disability,
      and Health (ICF) framework. The non-parametric Wilcoxon signed-rank test was
      applied to data from the first two sections of the Communication Profile-Adapted.
      Qualitative analysis was conducted on the final section. The data provided
      evidence of statistically significant positive changes in caregiver perceptions
      of communication at the levels of Body Structure and Function, and Activities for
      Communication. Also, analysis of the Participation for Communication section
      revealed some expansion to the children's social activities. The potential impact
      of the home-based intervention would benefit from investigation on a larger
      scale. Limitations of the study are discussed.

PMID- 25379628
TI  - Structures and energies of Cu clusters on Fe and Fe3C surfaces from density
      functional theory computation.
AB  - Spin-polarized density functional theory computations have been carried out to
      study the stable adsorption configurations of Cun (n = 1-7, 13) on Fe and Fe3C
      surfaces for understanding the initial stages of copper promotion in catalysis.
      At low coverage, two-dimensional aggregation is more preferred over dispersion
      and three-dimensional aggregation on the Fe(110) and Fe(100) surfaces as well as
      the metallic Fe3C(010) surfaces, while dispersion is more favorable over
      aggregation on the Fe(111) surface. On the Fe3C(001) and Fe3C(100) surfaces with
      exposed iron and carbon atoms, the adsorbed Cu atoms prefer dispersion at low
      coverage, while aggregation along the iron regions at high coverage. On the iron
      surfaces, the adsorption energies of Cun (n = 2-7) are highest on Fe(111), medium
      on Fe(100) and lowest on Fe(110). On the Fe3C surfaces, the adsorption energies
      of Cun (n = 1-3) are highest on Fe3C(100), medium on Fe3C(010) and lowest on
      Fe3C(001), while, for n = 4-7 and 13, Fe3C(010) has stronger adsorption than
      Fe3C(100). On the basis of their differences in electronegativity, the adsorbed
      Cu atoms can oxidize the metallic Fe(110), Fe(100) and Fe3C(010) surfaces and
      become negatively charged. On the Fe3C(001) and Fe3C(100) surfaces with exposed
      iron and carbon atoms, the adsorbed Cu atoms interacting with surface carbon
      atoms are oxidized and positively charged. Unlike the most stable Fe(110) and
      Fe3C(001) surfaces, where the Fe(110) surface has stronger Cu affinity than the
      Fe3C(001) surface, which is in agreement with the experimental finding, the less
      and least stable Fe3C(010) and Fe3C(100) surfaces have stronger Cu affinities
      than the Fe(110) and Fe(100) surfaces. Since less stable facets are not
      preferably formed thermodynamically, it is crucial to prepare such surfaces to
      explore Cu adsorption and promotion, and this provides challenges to surface
      sciences. 

PMID- 25379629
TI  - Proteomic and other mass spectrometry based "omics" biomarker discovery and
      validation in pediatric venous thromboembolism and arterial ischemic stroke:
      current state, unmet needs, and future directions.
AB  - Venous thromboembolism (VTE) and arterial ischemic stroke (AIS) are increasingly
      recognized health conditions in children, with both acute and chronic sequelae.
      Risk factors for, and pathogenesis of, VTE are readily related to three principal
      factors, consisting of venous stasis, endothelial damage, and the hypercoagulable
      state (i.e. thrombophilia), termed the triad of Virchow. In children, greater
      than 90% of VTE are provoked by an overt clinical risk factor, the most common of
      which is a central venous catheter. Risk factors for childhood-onset (beyond the
      neonatal period) AIS include sickle cell disease, infection, cerebral
      arteriopathy, and congenital cardiac disease. In perinatal AIS, risk factors are
      less well-defined, and have been hypothesized to include maternal-fetal
      conditions. While some acquired and inherited thrombophilias have been associated
      with increased risk of incident and/or recurrent VTE and AIS, knowledge of other
      diagnostic and prognostic biomarkers of VTE/AIS in children remains quite
      limited. To date, very few published studies have employed plasma mass
      spectrometry-based "omics" approaches (proteomics, lipidomics or metabolomics).
      Ongoing and future research efforts involving multicenter prospective study
      derived plasma biobanks in pediatric VTE (such as the Kids-DOTT trial) and AIS
      (including VIPS) along with new multi-omics-compatible sample processing methods
      offer fertile opportunities for discovery and validation of both novel risk
      factors and prognostic markers, with great potential to achieve improved
      prognostic stratification in these diseases. 

PMID- 25379630
TI  - Barriers to use of refractive services in Mozambique.
AB  - PURPOSE: Uncorrected refractive error remains a leading cause of visual
      impairment (VI) across the globe with Mozambique being no exception. The
      establishment of an optometry profession in Mozambique that is integrated into
      the public health system denotes significant progress with refractive services
      becoming available to the population. As the foundations of a comprehensive
      refractive service have now been established, this article seeks to understand
      what barriers may limit their uptake by the general population and inform
      decision making on improved service delivery. METHODS: A community-based cross
      sectional study using two-stage cluster sampling was conducted. Participants with
      VI were asked to identify barriers that were reflective of their experiences and
      perceptions of accessing refractive services. A total of 4601 participants were
      enumerated from 76 clusters in Nampula, Mozambique. RESULTS: A total of 1087
      visually impaired participants were identified (884 with near and 203 with
      distance impairment). Cost was the most frequently cited barrier, identified by
      more than one in every two participants (53%). Other barriers identified included
      lack of felt need (20%), distance to travel (15%), and lack of awareness (13%).
      In general, no significant influence of sex or type of VI on barrier selection
      was found. Location had a significant impact on the selection of several
      barriers. Pearson chi analysis indicated that participants from rural areas were
      found to feel disadvantaged regarding the distance to services (p <= 0.001) and
      adequacy of hospital services (p = 0.001). CONCLUSIONS: For a comprehensive
      public sector refractive service to be successful in Mozambique, those planning
      its implementation must consider cost and affordability. A clear strategy for
      overcoming lack of felt need will also be needed, possibly in the form of
      improved advocacy and health promotion. The delivery of refractive services in
      more remote rural areas merits careful and comprehensive consideration.

PMID- 25379631
TI  - Focal choroidal excavation associated with focal retinochoroiditis.
AB  - PURPOSE: To describe detailed spectral-domain optical coherence tomography (OCT)
      findings for two patients with focal choroidal excavation (FCE) associated with
      focal retinochoroiditis. CASE REPORT: Three eyes from two patients with FCE
      associated with focal retinochoroiditis were evaluated by funduscopy,
      fluorescence angiography, indocyanine green angiography, and spectral-domain OCT
      during follow-up. Both patients with focal retinochoroiditis developed new FCE
      after oral steroid treatment and two eyes showed regression of the FCE during the
      follow-up. Both eyes from one patient transformed from the conforming to the
      nonconforming type and neither of the eyes were stable during the follow-up.
      Ultimately, all eyes exhibited the conforming-type FCE. CONCLUSIONS: Focal
      choroidal excavation can be seen as a tomographic phenotype after the treatment
      of focal retinochoroiditis. Spectral-domain OCT was useful for detecting the
      development of FCE after the treatment and for observing FCE regression.

PMID- 25379632
TI  - Cone ratios in myopia and emmetropia: a pilot study.
AB  - PURPOSE: There is a suggestion that the long wavelength-sensitive (LWS)-to-middle
      wavelength-sensitive (MWS) cone ratio in the retina is associated with myopia.
      The aim was to measure the LWS/MWS amplitude modulation ratio, an estimate of the
      LWS/MWS cone ratio, in young adult emmetropes and myopes. METHODS: Multifocal
      visual evoked potentials were measured when the LWS and MWS cone systems were
      excited separately using the method of silent substitution. The 30 young adult
      participants (22 to 33 years) included 10 emmetropes (mean [+/-SD] refraction,
      +0.3 [+/-0.4] diopters [D]) and 20 myopes (mean [+/-SD] refraction, -3.4 [+/-1.7]
      D). RESULTS: The LWS/MWS amplitude modulation ratios ranged from 0.56 to 1.80 in
      the central 3- to 13-degree diameter ring and from 0.94 to 1.91 in the peripheral
      13- to 30-degree diameter ring. Within the central ring, the mean (+/-SD) ratios
      were 1.20 (+/-0.26) and 1.20 (+/-0.33) for the emmetropic and the myopic groups,
      respectively. For the peripheral ring, the mean (+/-SD) ratios were 1.48 (+/
      0.27) and 1.30 (+/-0.27), respectively. There were no significant differences in
      the ratios between the emmetropic and myopic groups for either the central (p =
      0.99) or peripheral (p = 0.08) rings. For the latter, more myopic refractive
      error was associated with lower LWS/MWS amplitude modulation ratio; the
      refraction explained 16% (p = 0.02) of variation in ratio. CONCLUSIONS: The
      relationship between the LWS/MWS amplitude modulation ratios and refraction at 13
      to 30 degrees indicates that a large longitudinal study of changes in refraction
      in persons with known cone ratio is required to determine if a low LWS/MWS cone
      ratio is associated with myopia development.

PMID- 25379633
TI  - pH response and molecular recognition in a low molecular weight peptide hydrogel.
AB  - In this article we report the preparation and characterization of a peptide-based
      hydrogel, which possesses characteristic rheological properties, is pH responsive
      and can be functionalized at its thiol function. The tripeptide N-(fluorenyl-9
      methoxycarbonyl)-L-Cys(acetamidomethyl)-L-His-L-Cys-OH 1 forms stable
      supramolecular aggregates in water leading to hydrogels above 1.5 wt%.
      Rheological analysis of the hydrogel revealed visco-elastic and shear thinning
      properties of samples containing 1.5 wt% of peptide 1. The hydrogel reversibly
      responds to pH changes. Below and above pH 6, electrostatic repulsion of the
      peptide results in a weakening of the three-dimensional gel network. Based on
      atomic force microscopy, small angle X-ray scattering and molecular dynamics
      simulations, it is proposed that the peptide assembles into nanostructures that
      tend to entangle at higher concentrations in water. The development of functional
      materials based on the peptide assemblies was possible via thiol-ene-click
      chemistry of the free thiol function at the C-terminal cysteine unit. As a proof
      of concept, the functionalization with adamantyl units to give 1-Ad was shown by
      molecular recognition of beta-cyclodextrin vesicles. These vesicles were used as
      supramolecular cross-linkers of the assemblies of peptide 1 mixed with peptide 1
      Ad leading to gel networks at a reduced peptide concentration.

PMID- 25379634
TI  - Cell-free RNA content in urine as a possible molecular diagnostic tool for clear
      cell renal cell carcinoma.
AB  - There is limited research on cell-free RNA (cf-RNA) in the urine of cancer
      patients. The present study was performed to detect the cf-RNA in the urine of
      patients with clear cell renal cell carcinoma (ccRCC). Ninety-five urine samples
      from ccRCC patients and 50 urine samples from control subjects were analyzed. The
      cf-RNA integrity index was calculated by using quantitative real-time RT-PCR
      assays of the small-sized fragment (106 bp) and the big-sized fragment (416 bp)
      in GAPDH mRNA. The initial analysis showed that cf-RNA was stable and detectable
      in the urine. The mean cf-RNA integrity index was significantly lower in the
      urine of ccRCC patients (mean: 0.07, 95%CI: 0.05-0.10) when compared with the
      urine from control subjects (mean: 0.25, 95%CI: 0.16-0.33) (p < 0.001). The value
      of the area under the receiver-operating characteristic curve by using the cf-RNA
      integrity index for the diagnosis of ccRCC was 0.858 with a sensitivity of 68.0%
      and a specificity of 92.6%. Moreover, the small-sized VEGF mRNA fragment (98 bp)
      was detected in 31 of 50 urine samples of patients with ccRCC and in only 2 of 50
      urine samples of control subjects (p < 0.001) while the detection of the big
      sized (420 bp) VEGF mRNA fragment was an infrequent event. Our findings suggest
      that the small-sized cf-RNA in urine was more abundant in cancer patients. The
      tumor-related gene VEGF mRNA fragment was detectable in the urine of cancer
      patients. Our finding may provide a new molecular assay for the diagnosis of
      renal cell carcinoma. 

PMID- 25379635
TI  - Synchrotron applications to f-element research in the nuclear fuel cycle.
AB  - Synchrotron-based techniques are increasingly used to characterize radioactive
      materials and elucidate determinant processes relevant to the nuclear fuel cycle.
      Many recent advances are driven by the need to characterize such materials with
      high resolution, for example spatial resolution for studies of localized
      components of heterogeneous systems and energy resolution for characterising the
      5f-element oxidation state. Examples of synchrotron-based investigations into f
      element chemistry are presented, which illustrate utilizing such high resolution,
      while pointing out various aspects of synchrotron R&D related to the nuclear fuel
      cycle. Specifically an example related to separation chemistry performance, an
      example elucidating immobilisation processes in bedrock, and high energy X-ray
      emission spectral fingerprint for hexavalent uranium are summarised. Synchrotron
      based tools are providing insight into f-element chemistry and geochemistry and
      are providing data for benchmarking theoretical calculations; the future looks
      bright. 

PMID- 25379636
TI  - A highly efficient asymmetric synthesis of quaternary stereocenter-containing
      indolizidine and quinolizidine alkaloids using aldehydes, nitroalkenes, and
      unactivated cyclic ketimines.
AB  - A highly efficient approach for the construction of indolizidines and
      quinolizidines bearing a bridged quaternary stereocenter has been established in
      a one-pot fashion using aldehydes, nitroalkenes, and cyclic ketimines with
      excellent enantioselectivities and in high yields. Moreover, this method could be
      applied to the synthesis of indolizidines in the gram scale. 

PMID- 25379637
TI  - Supplementation with selenium can influence nausea, fatigue, physical, renal, and
      liver function of children and adolescents with cancer.
AB  - The drugs used in chemotherapy treatments have little specificity, attack tumor
      cells, and also injure proliferative tissues. Knowledge of the functions of
      micronutrients has greatly increased, especially of Selenium (Se) that presents
      immunomodulatory and antitumor functions. The present study evaluated the health
      related quality of life of patients undergoing chemotherapy for the treatment of
      leukemias and lymphomas (LL) and solid tumors (ST) while receiving Selenium (Se)
      supplementation. This is a randomized, double-blind, crossover study that
      evaluated the quality of life (EORTC-QLQ-C30 questionnaire), renal and liver
      functions of patients supplemented with Se. There was no statistically
      significant alteration in LL patients. However, the fatigue and nausea scores
      after 30 days did decrease in this group as well as in the ST group. After 1 year
      supplementation with Selenium, a more noticeable decrease in the scores
      concerning fatigue and nausea could be observed in the ST group, when compared
      with the beginning of the study. The LL patients also presented a decrease in the
      fatigue scores and physical functions. The kidney function as well as liver
      function has improved after Selenium supplementation when compared with the
      placebo intake in LL and ST patients, more remarkably in the LL group.
      Supplementation with Selenium promotes the reduction of chemotherapy side effects
      in cancer patients, especially by improving the conditions of patients with
      fatigue, nausea, and impaired physical function. Renal and liver functions have
      also improved.

PMID- 25379638
TI  - Perineal robot-assisted laparoscopic radical prostatectomy: feasibility study in
      the cadaver model.
AB  - PURPOSE: To evaluate the feasibility of perineal robot-assisted laparoscopic
      radical prostatectomy (P-RALP) in the cadaver model. METHODS: The prostate was
      assessed by ultrasonography and cystoscopy in the lithotomy position. After
      incision and subcutaneous dissection, a single-port device was placed and the
      robot was docked. The rectourethralis muscle was divided and the levator ani
      fibers were split. The Denonvilliers fascia was incised and the posterior
      prostate and seminal vesicles were dissected. The apex was dissected and the
      urethra was transected. The anterior and lateral planes were dissected and the
      prostate pedicles were clipped. The prostate was freed from the bladder neck and
      the vesicourethral anastomosis was performed. The robot was undocked and the
      wound was sutured in layers. Cystoscopy confirmed integrity of the anastomosis.
      The specimen was sent for histopathology examination. RESULTS: Nerve-sparing P
      RALP was successfully completed in three cadavers. Median time for setting was 23
      minutes. Time for posterior dissection was 15 minutes. Dissection of the apex and
      section of the urethra took 9 minutes. Time for anterolateral dissection was 14
      minutes. Time for bladder neck dissection was 7 minutes. Vesicourethral
      anastomosis took 8 minutes. Total operative time was 89 minutes. The prostate
      capsule was grossly intact and histopathology examination was negative for
      prostatic tissue in all distal urethral sections and in two of three bladder neck
      sections. CONCLUSIONS: P-RALP is feasible in the cadaver. Future studies should
      evaluate the feasibility of lymph node dissection through the same incision,
      clinical feasibility, and prospective comparisons with standard techniques.

PMID- 25379639
TI  - Effects of tetraethyl orthosilicate (TEOS) on the light and temperature stability
      of a pigment from Beta vulgaris and its potential food industry applications.
AB  - A novel, simple and inexpensive modification method using TEOS to increase the UV
      light, pH and temperature stability of a red-beet-pigment extracted from Beta
      vulgaris has been proposed. The effects on the molecular structure of betalains
      were studied by FTIR spectroscopy. The presence of betacyanin was verified by UV
      Vis spectroscopy and its degradation in modified red-beet-pigment was evaluated
      and compared to the unmodified red-beet-pigment; performance improvements of
      88.33%, 16.84% and 20.90% for UV light, pH and temperature stability were
      obtained, respectively,. Measurements of reducing sugars, phenol, and antioxidant
      contents were performed on unmodified and modified red-beet-pigment and losses of
      close to 21%, 54% and 36%, respectively, were found to be caused by the addition
      of TEOS. Polar diagrams of color by unmodified and modified red-beet-pigment in
      models of a beverage and of a yogurt were obtained and the color is preserved,
      although here is a small loss in the chromaticity parameter of the modified red
      beet-pigment. 

PMID- 25379640
TI  - Exogenous spermidine improves seed germination of white clover under water stress
      via involvement in starch metabolism, antioxidant defenses and relevant gene
      expression.
AB  - This study was designed to determine the effect of exogenous spermidine (Spd) (30
      MUM) on white clover seed germination under water stress induced by polyethylene
      glycol 6000. Use of seed priming with Spd improved seed germination percentage,
      germination vigor, germination index, root viability and length, and shortened
      mean germination time under different water stress conditions. Seedling fresh
      weight and dry weight also increased significantly in Spd-treated seeds compared
      with control (seeds primed with distilled water). Improved starch metabolism was
      considered a possible reason for this seed invigoration, since seeds primed with
      Spd had significantly increased alpha-amylase/beta-amylase activities, reducing
      sugar, fructose and glucose content and transcript level of beta-amylase gene but
      not transcript level of alpha-amylase gene. In addition, the physiological
      effects of exogenous Spd on improving seeds' tolerance to water deficit during
      germination were reflected by lower lipid peroxidation levels, better cell
      membrane stability and significant higher seed vigour index in seedlings.
      Enhanced antioxidant enzyme activities (superoxide dismutase, peroxidase,
      catalase and ascorbate peroxidase), ascorbate-glutathione cycle (ASC-GSH cycle)
      and transcript level of genes encoding antioxidant enzymes induced by exogenous
      Spd may be one of the critical reasons behind acquired drought tolerance through
      scavenging of reactive oxygen species (ROS) in water-stressed white clover seeds.
      The results indicate that Spd plays an important function as a stress-protective
      compound or physiological activator. 

PMID- 25379641
TI  - Dysidinoid A, an unusual meroterpenoid with anti-MRSA activity from the South
      China Sea sponge Dysidea sp.
AB  - An unusual meroterpenoid, dysidinoid A (1), was isolated from the South China Sea
      sponge Dysidea sp. Its structure was elucidated by extensive spectroscopic
      methods including HRESIMS and 2D NMR, and its absolute configuration was
      determined by single-crystal X-ray diffraction analysis. Dysidinoid A (1) is the
      first meroterpenoid from Nature bearing a 9,4-friedodrime skeleton and a 2,5
      dionepyrrole unit. Dysidinoid A (1) showed potent antibacterial activity against
      two strains of pathogenic bacteria methicillin-resistant Staphylococcus aureus
      (MRSA) with MIC90 values of 8.0 MUg/mL against both. 

PMID- 25379642
TI  - Deciphering the role of phytoalexins in plant-microorganism interactions and
      human health.
AB  - Phytoalexins are low molecular weight antimicrobial compounds that are produced
      by plants as a response to biotic and abiotic stresses. As such they take part in
      an intricate defense system which enables plants to control invading
      microorganisms. In this review we present the key features of this diverse group
      of molecules, namely their chemical structures, biosynthesis, regulatory
      mechanisms, biological activities, metabolism and molecular engineering. 

PMID- 25379643
TI  - Synthesis and biological evaluation of liguzinediol mono- and dual ester prodrugs
      as promising inotropic agents.
AB  - The potent positive inotropic effect, together with the relatively low safety
      risk of liguzinediol (LZDO), relative to currently available inotropic drugs, has
      prompted us to intensively research and develop LZDO as a potent positive
      inotropic agent. In this study, to obtain LZDO alternatives for oral chronic
      administration, a series of long-chain fatty carboxylic mono- and dual-esters of
      LZDO were synthesized, and preliminarily evaluated for physicochemical properties
      and bioconversion. Enhanced lipophilic properties and decreased solubility of the
      prodrugs were observed as the side chain length increased. All esters showed
      conspicuous chemical stability in phosphate buffer (pH 7.4). Moreover, the
      enzymatic hydrolysis of esters in human plasma and human liver microsomes
      confirmed that the majority of esters were converted to LZDO, with release
      profiles that varied due to the size and structure of the side chain. In vivo
      pharmacokinetic studies following oral administration of monopivaloyl (M5),
      monodecyl (M10) and monododecyl (M12) esters demonstrated the evidently extended
      half-lives relative to LZDO dosed alone. In particular the monopivaloyl ester M5
      exhibited an optimal pharmacokinetic profile with appropriate physiochemical
      characteristics. 

PMID- 25379644
TI  - Anti-inflammatory effect of methylpenicinoline from a marine isolate of
      Penicillium sp. (SF-5995): inhibition of NF-kappaB and MAPK pathways in
      lipopolysaccharide-induced RAW264.7 macrophages and BV2 microglia.
AB  - In the course of a search for anti-inflammatory metabolites from marine-derived
      fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin
      sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO)
      production by suppressing the expression of inducible NO synthase (iNOS) in
      RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2
      (PGE2) production by suppressing cyclooxygenase-2 (COX-2) expression in a
      concentration-dependent manner (from 10 MUM to 80 MUM) without affecting cell
      viability. In addition, compound 1 reduced the production of the pro-inflammatory
      cytokine interleukin-1beta (IL-1beta). In a further study designed to elucidate
      the mechanism of its anti-inflammatory effects, compound 1 was shown to block
      nuclear factor-kappa B (NF-kappaB) activation in LPS-induced RAW264.7 macrophages
      and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-alpha
      (IkappaB-alpha), thereby suppressing the nuclear translocation of NF-kappaB
      dimers, namely p50 and p65, that are known to be crucial molecules associated
      with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation
      of mitogen-activated protein kinase (MAPK) pathways. Taken together, the results
      suggest that compound 1 might be a valuable therapeutic agent for the treatment
      of anti-inflammatory and anti-neuroinflammatory diseases. 

PMID- 25379645
TI  - Analysis on the interaction domain of VirG and apyrase by pull-down assay.
AB  - VirG is outer membrane protein of Shigella and affects the spread of Shigella.
      Recently it has been reported that apyrase influences the location of VirG,
      although the underlying mechanism remains poorly understood. The site of
      interaction between apyrase and VirG is the focus of our research. First we
      constructed recombinant plasmid pHIS-phoN2 and pS-(v1-1102, v53-758, v759-1102,
      v53-319, v320-507, v507-758) by denaturation-renaturation, the phoN2:kan mutant
      of Shigella flexneri 5a M90T by a modified version of the lambda red
      recombination protocol originally described by Datsenko and Wanner and the
      complemented strain M90TDeltaphoN2/pET24a(PhisphoN2). Second, the recombinant
      plasmid pHIS-phoN2 and the pS-(v1-1102, v53-758, v759-1102, v53-319, v320-507,
      v507-758) were transformed into E. coli BL21 (DE3) and induced to express the
      fusion proteins. Third, the fusion proteins were purified and the interaction of
      VirG and apyrase was identified by pull-down. Fourth, VirG was divided and the
      interaction site of apyrase and VirG was determined. Finally, how apyrase affects
      the function of VirG was analyzed by immunofluorescence. Accordingly, the results
      provided the data supporting the fact that apyrase combines with the alpha-domain
      of VirG to influence the function of VirG. 

PMID- 25379646
TI  - Coupled microwave/photoassisted methods for environmental remediation.
AB  - The microwave-induced acceleration of photocatalytic reactions was discovered
      serendipitously in the late 1990s. The activity of photocatalysts is enhanced
      significantly by both microwave radiation and UV light. Particularly relevant,
      other than as a heat source, was the enigmatic phenomenon of the non-thermal
      effect(s) of the microwave radiation that facilitated photocatalyzed reactions,
      as evidenced when examining various model contaminants in aqueous media. Results
      led to an examination of the possible mechanism(s) of the microwave effect(s). In
      the present article we contend that the microwaves' non-thermal effect(s) is an
      important factor in the enhancement of TiO2-photoassisted reactions involving the
      decomposition of organic pollutants in model wastewaters by an integrated
      (coupled) microwave-/UV-illumination method (UV/MW). Moreover, such coupling of
      no less than two irradiation methods led to the fabrication and ultimate
      investigation of microwave discharged electrodeless lamps (MDELs) as optimal
      light sources; their use is also described. The review focuses on the enhanced
      activity of photocatalytic reactions when subjected to microwave radiation and
      concentrates on the authors' research of the past few years. 

PMID- 25379647
TI  - Absorbability, mechanism and structure-property relationship of three phenolic
      acids from the flowers of Trollius chinensis.
AB  - The absorption properties, mechanism of action, and structure-property
      relationship of three phenolic acids isolated from the flowers of Trollius
      chinensis Bunge, namely, proglobeflowery acid (PA), globeflowery acid (GA) and
      trolloside (TS), were investigated using the human Caco-2 cell monolayer model.
      The results showed that these three phenolic acids were transported across the
      Caco-2 cell monolayer in a time and concentration dependent manner at the Papp
      level of 10-5 cm/s, and their extent of absorption correlated with their polarity
      and molecular weight. In conclusion, all three of these compounds were easily
      absorbed through passive diffusion, which implied their high bioavailability and
      significant contribution to the effectiveness of T. chinensis. 

PMID- 25379648
TI  - Quinone reductase 2 is an adventitious target of protein kinase CK2 inhibitors
      TBBz (TBI) and DMAT.
AB  - Quinone reductase 2 (NQO2) exhibits off-target interactions with two protein
      kinase CK2 inhibitors, 4,5,6,7-1H-tetrabromobenzimidazole (TBBz) and 2
      dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT). TBBz and DMAT induce
      apoptosis in cells expressing an inhibitor-resistant CK2, suggesting that the
      interaction with NQO2 may mediate some of their pharmacological effects. In this
      study, we have fully characterized the binding of TBBz and DMAT to NQO2.
      Fluorescence titrations showed that TBBz and DMAT bind oxidized NQO2 in the low
      nanomolar range; in the case of TBBz, the affinity for NQO2 was 40-fold greater
      than its affinity for CK2. A related CK2 inhibitor, 4,5,6,7
      tetrabromobenzotriazole (TBB), which failed to cause apoptosis in cells
      expressing inhibitor-resistant CK2, binds NQO2 with an affinity 1000-fold lower
      than those of TBBz and DMAT. Kinetic analysis indicated that DMAT inhibits NQO2
      by binding with similar affinities to the oxidized and reduced forms. Crystal
      structure analysis showed that DMAT binds reduced NQO2 in a manner different from
      that in the oxidized state. In oxidized NQO2, TBBz and DMAT are deeply buried in
      the active site and make direct hydrogen and halogen bonds to the enzyme. In
      reduced NQO2, DMAT occupies a more peripheral region and hydrogen and halogen
      bonds with the enzyme are mediated through three water molecules. Therefore,
      although TBB, TBBz, and DMAT are all potent inhibitors of CK2, they exhibit
      different activity profiles toward NQO2. We conclude that the active site of NQO2
      is fundamentally different from the ATP binding site of CK2 and the inhibition of
      NQO2 by CK2 inhibitors is adventitious. 

PMID- 25379649
TI  - A superior photocatalytic performance of a novel Bi2SiO5 flower-like microsphere
      via a phase junction.
AB  - A phase junction over a Bi(2)SiO(5) photocatalyst with the orthorhombic
      Bi(2)SiO(5) and the tetragonal Bi(2)SiO(5) structure was successfully synthesized
      via an ion exchange method using BiOBr solid microspheres as the sacrificial
      template. In the meantime, the as-prepared Bi(2)SiO(5) phase junction possesses a
      novel morphology of a flower-like microsphere with nanoparticles evenly embedded
      in its nano-petals. It was found that the Bi(2)SiO(5) phase junction not only
      showed a highly enhanced photocatalytic activity and excellent durability under
      UV or simulated solar irradiation, but also showed a remarkable visible-light
      activity for photo-degradation of phenol. Experimental results reveal that the
      tetragonal Bi(2)SiO(5) phase in this phase junction possesses a narrower band
      gap, thus leading to its extended light absorption. The efficient charge
      separation via a phase junction would make a great contribution to its highly
      enhanced photocatalytic activity under UV or simulated solar irradiation. The
      high efficiency in the degradation of organic pollutants makes the as-prepared
      photocatalyst a promising candidate for photocatalytic environmental
      purification.

PMID- 25379650
TI  - Abdominal pain in systemic lupus erythematosus: lupus enteritis, mesenteric
      thrombosis, or median arcuate ligament syndrome?

PMID- 25379651
TI  - Stimuli responsive fibrous hydrogels from hierarchical self-assembly of a
      triblock copolypeptide.
AB  - In this work, the self-assembly behavior and pH responsiveness of a triblock
      copolypeptide in aqueous media are demonstrated. The copolypeptide was composed
      of a central pH responsive poly(l-glutamic acid) (PGA), flanked by two
      hydrophobic poly(l-alanine) blocks (PAla) (PAla5-PGA11-PAla5). This system showed
      a pH-responsive transition from short tapes to spherical aggregates by increasing
      the pH, as a result of deprotonation of the PGA block and a conformational change
      from alpha-helix to random coil. Increasing the ionic strength to physiological
      conditions (0.15 M) has triggered fibrillar self-assembly through intermolecular
      hydrogen bonding of PAla end-blocks that form beta-sheet nanostructures, in
      conjunction with charge screening of the central random coil PGA segments. At
      elevated concentrations a thermo-responsive free supporting hydrogel was
      obtained, consisting of rigid beta-sheet based twisted superfibers, resulting
      from hierarchical self-assembly of the copolypeptide. Yet, morphological
      transformation of this nanostructure was observed upon switching the pH from
      physiological conditions to pH 4. An unexpected morphology constituted of alpha
      helix-based giant nanobelts was observed as a consequence of the secondary
      peptide transitions. 

PMID- 25379652
TI  - The beneficial properties of marine polysaccharides in alleviation of allergic
      responses.
AB  - Marine polysaccharides have been found as the principle component in cell wall
      structures of seaweeds or exoskeletons of crustaceans. Due to numerous
      pharmaceutical properties of marine polysaccharides such as antioxidant, anti
      inflammatory, antiallergic, antitumor, antiobesity, antidiabetes, anticoagulant,
      antiviral, immunomodulatory, cardioprotective, and antihepatopathy activities,
      they have been applied in many fields of biomaterials, food, cosmetic, and
      pharmacology. Recently, several marine polysaccharides such alginate, porphyran,
      fucoidan, and chitin and its derivatives have been evidenced as downregulators of
      allergic responses due to enhancement of innate immune system, alteration of
      Th1/Th2 balance forward to Th1 cells, inhibition of IgE production, and
      suppression of mast cell degranulation. This contribution, therefore, focuses on
      antiallergic properties of marine polysaccharides and emphasizes their potential
      application as bioactive food ingredients as well as nutraceuticals for
      prevention of allergic disorders. 

PMID- 25379653
TI  - The association between obesity and outcomes in critically ill patients.
AB  - BACKGROUND: Obesity rates are increasing worldwide, particularly in North
      America. The impact of obesity on the outcome of critically ill patients is
      unclear. METHODS: A prospective observational cohort study of consecutive
      patients admitted to a tertiary critical care unit in Canada between January 10,
      2008 and March 31, 2009 was conducted. Exclusion criteria were age <18 years,
      admission <24 h, planned cardiac surgery, pregnancy, significant ascites,
      unclosed surgical abdomen and brain death on admission. Height, weight and
      abdominal circumference were measured at the time of intensive care unit (ICU)
      admission. Coprimary end points were ICU mortality and a composite of ICU
      mortality, reintubation, ventilator-associated pneumonia, line sepsis and ICU
      readmission. Subjects were stratified as obese or nonobese, using two separate
      metrics: body mass index (BMI) >= 30 kg/m(2) and a novel measurement of 75th
      percentile for waist-to-height ratio (WHR). RESULTS: Among 449 subjects with a
      BMI >= 18.5 kg/m(2), both BMI and WHR were available for comparative analysis in
      348 (77.5%). Neither measure of obesity was associated with the primary end
      points. BMI >= 3 0 kg/m(2) was associated with a lower odds of six-month
      mortality than the BMI <30 kg/m(2) group (adjusted OR 0.59 [95% CI 0.36 to 0.97];
      P=0.04) but longer intubation times (adjusted RR 1.56 [95% CI 1.17 to 2.07];
      P=0.003) and longer ICU length of stay (adjusted RR 1.67 [95% CI 1.21 to 2.31];
      P=0.002). Conversely, measurement of 75th percentile for WHR was associated only
      with decreased ICU readmission (OR 0.23 [95% CI 0.07 to 0.79]; P=0.02).
      CONCLUSIONS: Obesity was not necessarily associated with worse outcomes in
      critically ill patients.

PMID- 25379654
TI  - Lung transplantation from donors after circulatory death using portable ex vivo
      lung perfusion.
AB  - BACKGROUND: Donation after circulatory death is a novel method of increasing the
      number of donor lungs available for transplantation. Using organs from donors
      after circulatory death has the potential to increase the number of transplants
      performed. METHODS: Three bilateral lung transplants from donors after
      circulatory death were performed over a six-month period. Following organ
      retrieval, all sets of lungs were placed on a portable ex vivo lung perfusion
      device for evaluation and preservation. RESULTS: Lung function remained stable
      during portable ex vivo perfusion, with improvement in partial pressure of
      oxygen/fraction of inspired oxygen ratios. Mechanical ventilation was
      discontinued within 48 h for each recipient and no patient stayed in the
      intensive care unit longer than eight days. There was no postgraft dysfunction at
      72 h in two of the three recipients. Ninety-day mortality for all recipients was
      0% and all maintain excellent forced expiratory volume in 1 s and forced vital
      capacity values post-transplantation. CONCLUSION: The authors report excellent
      results with their initial experience using donors after circulatory death after
      portable ex vivo lung perfusion. It is hoped this will allow for the most
      efficient use of available donor lungs, leading to more transplants and fewer
      deaths for potential recipients on wait lists.

PMID- 25379655
TI  - The association between sleep-disordered breathing and magnetic resonance imaging
      findings in a pediatric cohort with Chiari 1 malformation.
AB  - BACKGROUND: The prevalence of sleep-disordered breathing (SDB) reported in the
      literature for Chiari malformation type 1 (CM1) is uniformly high (24% to 70%).
      In Canada, there is limited access to pediatric polysomnography (PSG). Therefore,
      the identification of clinical features would be invaluable for triaging these
      children. OBJECTIVE: To identify demographic features, clinical symptoms/signs
      and radiological findings associated with SDB in a large pediatric cohort with
      CM1. METHODS: A retrospective review was conducted on children with CM1 who
      underwent baseline PSG. Data were collected on patient demographics (age, sex,
      weight, height, body mass index), clinical symptoms (chart review and clinical
      questionnaires), diagnostic imaging of the brain and cervicothoracic spine, and
      medical history at the time of referral. RESULTS: A total of 68 children were
      included in the review. The mean (+/- SD) age of the children at the time of PSG
      was 7.33 +/- 4.01 years; 56% (n=38) were male. There was a 49% prevalence of SDB
      in this cohort based on the overall apnea-hypopnea index. Obstructive sleep apnea
      was the predominant type of SDB. Tonsillar herniation was significantly
      correlated with obstructive apnea-hypopnea index (r=0.24; P=0.036). CONCLUSIONS:
      A direct relationship between the degree of cerebellar tonsillar herniation and
      obstructive sleep apnea was demonstrated. However, further prospective studies
      that include neurophysiological assessment are needed to further translate the
      central nervous system imaging findings to predict the presence of SDB.

PMID- 25379656
TI  - Is there an association between symptoms of anxiety and depression and quality of
      life in patients with chronic obstructive pulmonary disease?
AB  - BACKGROUND: In addition to symptoms, such as dyspnea and fatigue, patients with
      chronic obstructive pulmonary disease (COPD) also experience mood disturbances.
      OBJECTIVE: To explore the relationships between health-related quality of life
      measures collected from patients with stable COPD and a commonly used measure of
      depression and anxiety. METHODS: The present analysis was a retrospective study
      of patients with COPD enrolled in a pulmonary rehabilitation program. Hospital
      Anxiety and Depression Scale (HADS), Chronic Respiratory Disease Questionnaire
      (CRQ), Medical Research Council dyspnea scale and 6 min walk test data were
      collected. Statistical analyses were performed using Spearman's correlations, and
      categorical regression and categorical principal component analysis were
      interpreted using the biplot methodology. RESULTS: HADS anxiety scores retrieved
      from 80 patients were grouped as 'no anxiety' (n=43 [54%]), 'probable anxiety'
      (n=21 [26%]) and 'presence of anxiety' (n=16 [20%]). HADS depression scores were
      similarly grouped. There was a moderate relationship between the anxiety subscale
      of the HADS and both the emotional function (r=-0.519; P<0.01) and mastery (r=
      0.553; P<0.01) domains of the CRQ. Categorical regression showed that the CRQ
      mastery domain explained 40% of the total variation in anxiety. A principal
      component analysis biplot showed that the highest distance between the groups was
      along the mastery domain, which separated patients without feelings of anxiety
      from those with anxiety. However, none of the CRQ domains were able to
      discriminate the three depression groups. CONCLUSIONS: The CRQ-mastery domain may
      identify symptoms of anxiety in patients with COPD; however, the relationship is
      not strong enough to use the CRQ-mastery domain as a surrogate measure. None of
      the CRQ domains were able to discriminate the three depression groups (no
      depression, probable and presence); therefore, specific, validated tools to
      identify symptoms of depression should be used.

PMID- 25379657
TI  - Positive contrast of SPIO-labeled cells by off-resonant reconstruction of 3D
      radial half-echo bSSFP.
AB  - This article describes a new acquisition and reconstruction concept for positive
      contrast imaging of cells labeled with superparamagnetic iron oxides (SPIOs).
      Overcoming the limitations of a negative contrast representation as gained with
      gradient echo and fully balanced steady state (bSSFP), the proposed method
      delivers a spatially localized contrast with high cellular sensitivity not
      accomplished by other positive contrast methods. Employing a 3D radial bSSFP
      pulse sequence with half-echo sampling, positive cellular contrast is gained by
      adding artificial global frequency offsets to each half-echo before image
      reconstruction. The new contrast regime is highlighted with numerical intravoxel
      simulations including the point-spread function for 3D half-echo acquisitions.
      Furthermore, the new method is validated on the basis of in vitro cell phantom
      measurements on a clinical MRI platform, where the measured contrast-to-noise
      ratio (CNR) of the new approach exceeds even the negative contrast of bSSFP.
      Finally, an in vivo proof of principle study based on a mouse model with a clear
      depiction of labeled cells within a subcutaneous cell islet containing a cell
      density as low as 7 cells/mm(3) is presented. The resultant isotropic images show
      robustness to motion and a high CNR, in addition to an enhanced specificity due
      to the positive contrast of SPIO-labeled cells.

PMID- 25379659
TI  - All-cause pneumonia hospitalizations in children <2 years old in sweden, 1998 to
      2012: impact of pneumococcal conjugate vaccine introduction.
AB  - BACKGROUND: In late 2007, some Swedish County Councils started 7-valent
      pneumococcal conjugate vaccine (PCV7) implementation for children, and PCV7 was
      included in the national immunization program in 2009. By 2010, both PCV10 and
      PCV13 were licensed, and the selection of vaccine was subject to County Councils
      tenders. This study investigated the impact of the order of PCV introduction into
      vaccination programs on the incidence of all-cause pneumonia hospitalizations in
      children <2 years-old. METHODS: Using population-based data from the publicly
      available National Inpatient Registry, the incidence of inpatient pneumonia (ICD
      10 J12-J18) hospitalizations by County Councils among children <2 years old was
      identified between 1998 and 2012. Incidence rate ratios (IRR; 95% CI) were
      calculated during the nationwide implementation of PCV7 and then between County
      Councils, as based on the higher-valent vaccine chosen for a program. RESULTS:
      There was a lower risk of all-cause pneumonia hospitalization among <2 year-old
      children following the introduction of PCV7, as compared to the pre-PCV7 period
      (0.77; 0.63-0.93). A decreased risk of all-cause pneumonia was also observed in
      the County Councils that followed the order PCV7 then PCV13 (0.82; 0.66-1.01),
      while no trend was observed in County Councils with a program in the order PCV7
      then PCV10 (1.03; 0.82-1.30). When comparing the higher-valent vaccines, there
      was a 21% (0.79; 0.66-0.96) lower risk for childhood pneumonia hospitalization in
      County Councils finally using PCV13 as compared to the experience in County
      Councils that ultimately adopted PCV10. CONCLUSIONS: Among children <2 years-old,
      all-cause pneumonia hospitalizations were significantly reduced by 23% one to two
      years after introduction of PCV7 vaccination in Sweden. In those County Councils
      that next introduced PCV13, a further decline in all-cause pneumonia
      hospitalization was observed, in contrast to those County Councils that followed
      with PCV10; this 21% lower risk for childhood pneumonia hospitalization was
      statistically significant.

PMID- 25379660
TI  - Machine-driven versus manual insertion mode: influence on primary stability of
      orthodontic mini-implants.
AB  - PURPOSE: The study aimed to explore the effect of the insertion method on maximal
      insertion torque as a measure of primary stability while controlling for the
      effect of cortical bone thickness, mini-implant length and diameter, and vertical
      insertion force on insertion torque. METHODS: Six types of mini-implants (Dual
      Top; Jeil Medical, Corp.) with diameters of 1.4, 1.6, and 2.0 mm and lengths of 6
      and 8 mm were inserted manually and in a machine-driven mode into pig rib bone
      samples, and experiments were repeated 10 times, which totaled 120 tested
      implants in 120 pig rib samples. Cortical bone thickness was measured with a
      sliding caliper, whereas insertion torque and vertical insertion forces were
      recorded with a specially designed device. RESULTS: Significant predictors of
      better primary stability are thicker cortical bone (explaining 24.2% of
      variability), wider diameter (20.6%), manual insertion (9.9%), greater length
      (3.7%), higher maximal vertical insertion force (2.2%), and lower vertical force
      at maximal insertion torque (1.4%). CONCLUSIONS: Manual insertion is associated
      with higher primary stability of orthodontic mini-implants than mechanical
      insertion, but thicker cortical bone and larger implant diameter seem to be
      stronger predictors of primary stability.

PMID- 25379658
TI  - 4-Phenylbutyrate attenuates the ER stress response and cyclic AMP accumulation in
      DYT1 dystonia cell models.
AB  - Dystonia is a neurological disorder in which sustained muscle contractions induce
      twisting and repetitive movements or abnormal posturing. DYT1 early-onset primary
      dystonia is the most common form of hereditary dystonia and is caused by deletion
      of a glutamic acid residue (302/303) near the carboxyl-terminus of encoded
      torsinA. TorsinA is localized primarily within the contiguous lumen of the
      endoplasmic reticulum (ER) and nuclear envelope (NE), and is hypothesized to
      function as a molecular chaperone and an important regulator of the ER stress
      signaling pathway, but how the mutation in torsinA causes disease remains
      unclear. Multiple lines of evidence suggest that the clinical symptoms of
      dystonia result from abnormalities in dopamine (DA) signaling, and possibly
      involving its down-stream effector adenylate cyclase that produces the second
      messenger cyclic adenosine-3', 5'-monophosphate (cAMP). Here we find that
      mutation in torsinA induces ER stress, and inhibits the cyclic adenosine-3', 5'
      monophosphate (cAMP) response to the adenylate cyclase agonist forskolin. Both
      defective mechanins are corrected by the small molecule 4-phenylbutyrate (4-PBA)
      that alleviates ER stress. Our results link torsinA, the ER-stress-response, and
      cAMP-dependent signaling, and suggest 4-PBA could also be used in dystonia
      treatment. Other pharmacological agents known to modulate the cAMP cascade, and
      ER stress may also be therapeutic in dystonia patients and can be tested in the
      models described here, thus supplementing current efforts centered on the
      dopamine pathway.

PMID- 25379661
TI  - Occlusal contact of fixed implant prostheses using functional bite impression
      technique.
AB  - OBJECTIVE: Functional bite impression (FBI) has been described as a definitive
      impression made under occlusal force after functional generated path (FGP)
      recording. This study compared the accuracy of occlusal contact of implant-fixed
      prostheses using the FBI technique and the conventional impression technique.
      METHODS: Twelve subjects, each missing a single premolar or molar, were selected
      for this study. The conditions of the occlusal contacts were identified by the
      modified transillumination method. The occlusal contact condition was determined
      by comparing the rate of change in the occlusal contact area of the implant-fixed
      prostheses and both adjacent teeth before and after occlusal adjustment. RESULTS:
      The rate of change in the occlusal contact area using the FBI technique was 96%,
      and the rate using the conventional technique was 54%. The occlusal contact of
      implant prostheses using the FBI technique revealed better accuracy than that of
      the conventional technique. CONCLUSIONS: Regarding the FBI technique, a precise
      and functional prosthesis could be produced by completing the maxillomandibular
      registration, impression, and FGP at the same time.

PMID- 25379662
TI  - Osteotome sinus floor elevation procedure for first molar single-gap implant
      rehabilitation: a case series.
AB  - INTRODUCTION: This case series describes single implant rehabilitation in the
      maxillary first molar sites. It aims to show the surgical approaches carried out
      versus the residual bone height (RBH) and to evaluate implant success rate and
      bone anchorage height after 1 year. MATERIALS AND METHODS: Placement of 10-mm
      long tapered bone level implants was carried out according to the RBH: when RBH
      >=10 mm, standard implant placement; when 6 mm < RBH < 10 mm, osteotome sinus
      floor elevation procedure (OSFE) without graft; and, when RBH <=6 mm, OSFE with
      graft. RESULTS: Fourteen patients received 15 implants in a mean RBH of 5.0 +/-
      2.4 mm (range, 2.0-11.0 mm). One implant was placed with a standard placement
      technique, 4 using OSFE without graft, and 10 using OSFE with graft. The 1-year
      success rate was 100%, and mean bone anchorage height reached at least 9.5 mm.
      CONCLUSIONS: Almost all cases of maxillary single implant rehabilitation might be
      performed by using OSFE. In the extremely atrophic maxilla, simultaneous grafting
      ensures implant embedding in bone.

PMID- 25379663
TI  - Follow-up study of dental implants with bioactive oxide films on bone tissue
      healing and osseointegration: clinical radiography and bone quality analysis.
AB  - OBJECTIVE: The purpose of this study was to investigate osseointegration and bone
      stress resulted during the first 3 months after the installation of functional
      implants modified with bioactive oxide. METHODS: Several studies have
      investigated finite element models for dental implants; however, only a few have
      examined a model for the implants during different stages of osseointegration. In
      this study, mandible models were reconstructed using computer tomographic data,
      and bone qualities and stress distributions were investigated as well. RESULTS:
      Bone quality increased rapidly within the 3-month bone healing time. Data
      analysis indicated that the bone stresses increased with the progress of
      osseointegration, and the maximum stresses were obtained at the position around
      the first screw. CONCLUSION: The results confirmed that functional films could
      improve the biomechanical properties of the implants and promote the initial bone
      stability. Furthermore, potential clinical benefit can be obtained due to the
      inducing superior biomechanical behavior in dental implants.

PMID- 25379664
TI  - Primary stability of implants placed at different angulations in artificial bone.
AB  - INTRODUCTION: The aim of this study was to evaluate the primary stability (PS) of
      titanium implants with a progressive thread design and more thread stability in
      the apical threads placed in artificial bone materials. MATERIALS AND METHODS: A
      total of 120 implants were placed in commercially available polyurethane
      composite bone blocks. The angulations that were chosen to place the implants in
      bone types II and IV were 0, 10, and 20 degrees, respectively. The implant
      dimensions were 11 mm in length and 3.5 mm in diameter. Two clinicians placed all
      implants, and an independent examiner evaluated the PS using the Osstell (ISQ)
      and Periotest devices. The chi test was used to evaluate the statistical
      differences between the PS at different angulations. RESULTS: This study showed
      that there was a statistically significant difference (P = 0.02) of the PS
      values, when measured using the Periotest values, among all 3 angulations in both
      bone qualities. Tilted implants with 10 degrees, angulation had a better
      stability than conventionally placed implants. CONCLUSIONS: The PS of dental
      implants is higher for implants placed in type II when compared with type IV
      artificial bone. A higher stability was found for implants placed with 10-degree
      angulations.

PMID- 25379665
TI  - Piscivore-prey fish interactions: mechanisms behind diurnal patterns in prey
      selectivity in brown and clear water.
AB  - Environmental change may affect predator-prey interactions in lakes through
      deterioration of visual conditions affecting foraging success of visually
      oriented predators. Environmental change in lakes includes an increase in humic
      matter causing browner water and reduced visibility, affecting the behavioural
      performance of both piscivores and prey. We studied diurnal patterns of prey
      selection in piscivorous pikeperch (Sander lucioperca) in both field and
      laboratory investigations. In the field we estimated prey selectivity and prey
      availability during day and night in a clear and a brown water lake. Further,
      prey selectivity during day and night conditions was studied in the laboratory
      where we manipulated optical conditions (humic matter content) of the water.
      Here, we also studied the behaviours of piscivores and prey, focusing on foraging
      cycle stages such as number of interests and attacks by the pikeperch as well as
      the escape distance of the prey fish species. Analyses of gut contents from the
      field study showed that pikeperch selected perch (Perca fluviatilis) over roach
      (Rutilus rutilus) prey in both lakes during the day, but changed selectivity
      towards roach in both lakes at night. These results were corroborated in the
      selectivity experiments along a brown-water gradient in day and night light
      conditions. However, a change in selectivity from perch to roach was observed
      when the optical condition was heavily degraded, from either brown-stained water
      or light intensity. At longer visual ranges, roach initiated escape at distances
      greater than pikeperch attack distances, whereas perch stayed inactive making
      pikeperch approach and attack at the closest range possible. Roach anti-predatory
      behaviour decreased in deteriorated visual conditions, altering selectivity
      patterns. Our results highlight the importance of investigating both predator and
      prey responses to visibility conditions in order to understand the effects of
      degrading optical conditions on piscivore-prey interaction strength and thereby
      ecosystem responses to brownification of waters. 

PMID- 25379666
TI  - CT arteriography and venography in the evaluation of Pulsatile tinnitus with
      normal otoscopic examination.
AB  - OBJECTIVES/HYPOTHESIS: Our retrospective study aims to assess the ability of
      computed tomography arteriography and venography (CT A/V) to detect various
      findings that suggest a potential cause of pulsatile tinnitus and to examine the
      association between these findings and the side of pulsatile tinnitus. STUDY
      DESIGN: A retrospective review of CT arteriography and venography of 32 patients
      with established pulsatile tinnitus and normal otoscopic examination was
      performed. The scans were performed using a 64-slice multidetector scanner and
      were reviewed to look for findings that are known to cause pulsatile tinnitus.
      RESULTS: One or more findings that are known to cause pulsatile tinnitus were
      detected on the symptomatic side in 30 patients; on the asymptomatic side in 3
      patients, one patient with bilateral pulsatile tinnitus showed a potential cause
      of symptoms only on one side, and in one patient no potential cause could be
      identified. There is a significant association seen between the side of pulsatile
      tinnitus and various potential causes of pulsatile tinnitus detected (P < 0.001),
      between the side of pulsatile tinnitus and various potential venous cause
      detected (P < 0.001), and between the side of pulsatile tinnitus and the side of
      dominant venous system (P = 0.02). CONCLUSION: CT arteriography and venography is
      a useful tool in detecting many described potential causes of pulsatile tinnitus.
      Significant association is demonstrated between the side of pulsatile tinnitus
      and the potential causes of pulsatile tinnitus detected by CT arteriography and
      venography when the otoscopic examination is normal.

PMID- 25379667
TI  - Fluorescently activated cell sorting followed by microarray profiling of helper T
      cell subtypes from human peripheral blood.
AB  - BACKGROUND: Peripheral blood samples have been subjected to comprehensive gene
      expression profiling to identify biomarkers for a wide range of diseases.
      However, blood samples include red blood cells, white blood cells, and platelets.
      White blood cells comprise polymorphonuclear leukocytes, monocytes, and various
      types of lymphocytes. Blood is not distinguishable, irrespective of whether the
      expression profiles reflect alterations in (a) gene expression patterns in each
      cell type or (b) the proportion of cell types in blood. CD4+ Th cells are
      classified into two functionally distinct subclasses, namely Th1 and Th2 cells,
      on the basis of the unique characteristics of their secreted cytokines and their
      roles in the immune system. Th1 and Th2 cells play an important role not only in
      the pathogenesis of human inflammatory, allergic, and autoimmune diseases, but
      also in diseases that are not considered to be immune or inflammatory disorders.
      However, analyses of minor cellular components such as CD4+ cell subpopulations
      have not been performed, partly because of the limited number of these cells in
      collected samples. METHODOLOGY/PRINCIPAL FINDINGS: We describe fluorescently
      activated cell sorting followed by microarray (FACS-array) technology as a useful
      experimental strategy for characterizing the expression profiles of specific
      immune cells in the circulation. We performed reproducible gene expression
      profiling of Th1 and Th2, respectively. Our data suggest that this procedure
      provides reliable information on the gene expression profiles of certain small
      immune cell populations. Moreover, our data suggest that GZMK, GZMH, EOMES,
      IGFBP3, and STOM may be novel markers for distinguishing Th1 cells from Th2
      cells, whereas IL17RB and CNTNAP1 can be Th2-specific markers.
      CONCLUSIONS/SIGNIFICANCE: Our approach may help in identifying aberrations and
      novel therapeutic or diagnostic targets for diseases that affect Th1 or Th2
      responses and elucidating the involvement of a subpopulation of immune cells in
      some diseases.

PMID- 25379668
TI  - Tooth erosion and eating disorders: a systematic review and meta-analysis.
AB  - BACKGROUND: Eating disorders are associated with the highest rates of morbidity
      and mortality of any mental disorders among adolescents. The failure to recognize
      their early signs can compromise a patient's recovery and long-term prognosis.
      Tooth erosion has been reported as an oral manifestation that might help in the
      early detection of eating disorders. OBJECTIVES: The aim of this systematic
      review and meta-analysis was to search for scientific evidence regarding the
      following clinical question: Do eating disorders increase the risk of tooth
      erosion? METHODS: An electronic search addressing eating disorders and tooth
      erosion was conducted in eight databases. Two independent reviewers selected
      studies, abstracted information and assessed its quality. Data were abstracted
      for meta-analysis comparing tooth erosion in control patients (without eating
      disorders) vs. patients with eating disorders; and patients with eating disorder
      risk behavior vs. patients without such risk behavior. Combined odds ratios (ORs)
      and a 95% confidence interval (CI) were obtained. RESULTS: Twenty-three papers
      were included in the qualitative synthesis and assessed by a modified version of
      the Newcastle-Ottawa Scale. Fourteen papers were included in the meta-analysis.
      Patients with eating disorders had more risk of tooth erosion (OR = 12.4, 95%CI =
      4.1-37.5). Patients with eating disorders who self-induced vomiting had more risk
      of tooth erosion than those patients who did not self-induce vomiting (OR = 19.6,
      95%CI = 5.6-68.8). Patients with risk behavior of eating disorder had more risk
      of tooth erosion than patients without such risk behavior (Summary OR = 11.6,
      95%CI = 3.2-41.7). CONCLUSION: The scientific evidence suggests a causal
      relationship between tooth erosion and eating disorders and purging practices.
      Nevertheless, there is a lack of scientific evidence to fulfill the basic
      criteria of causation between the risk behavior for eating disorders and tooth
      erosion.

PMID- 25379669
TI  - Genotypic prediction of tropism of highly diverse HIV-1 strains from Cameroon.
AB  - BACKGROUND: The use of CCR5 antagonists involves determination of HIV-1 tropism
      prior to initiation of treatment. HIV-1 tropism can be assessed either by
      phenotypic or genotypic methods. Genotypic methods are extensively used for
      tropism prediction. However, their validation in predicting tropism of viral
      isolates belonging to group M non-B subtypes remains challenging. In Cameroon,
      the genetic diversity of HIV-1 strains is the broadest reported worldwide. To
      facilitate the integration of CCR5 antagonists into clinical practice in this
      region, there is a need to evaluate the performance of genotypic methods for
      predicting tropism of highly diverse group M HIV-1 strains. METHODS: Tropism of
      diverse HIV-1 strains isolated from PBMCs from Cameroon was determined using the
      GHOST cell assay. Prediction, based on V3 sequences from matched plasma samples,
      was determined using bioinformatics algorithms and rules based on position 11/25
      and net charge applied independently or combined according to Delobel's and
      Garrido's rules. Performance of genotypic methods was evaluated by comparing
      prediction generated with tropism assigned by the phenotypic assay. RESULTS:
      Specificity for predicting R5-tropic virus was high, ranging from 83.7% to 97.7%
      depending on the genotypic methods used. Sensitivity for X4-tropic viruses was
      fairly low, ranging from 33.3% to 50%. In our study, overall, genotypic methods
      were less able to accurately predict X4-tropic virus belonging to subtype
      CRF02_AG. In addition, it was found that of the methods we used the Garrido rule
      has the highest sensitivity rate of over 50% with a specificity of 93%.
      CONCLUSION: Our study demonstrated that overall, genotypic methods were less
      sensitive for accurate prediction of HIV-1 tropism in settings where diverse HIV
      1 strains co-circulate. Our data suggest that further optimization of genotypic
      methods is needed and that larger studies to determine their utility for tropism
      prediction of diverse HIV-1 strains may be warranted.

PMID- 25379670
TI  - Comparative metagenomic analysis of coral microbial communities using a reference
      independent approach.
AB  - By comparing the SEED and Pfam functional profiles of metagenomes of two
      Brazilian coral species with 29 datasets that are publicly available, we were
      able to identify some functions, such as protein secretion systems, that are
      overrepresented in the metagenomes of corals and may play a role in the
      establishment and maintenance of bacteria-coral associations. However, only a
      small percentage of the reads of these metagenomes could be annotated by these
      reference databases, which may lead to a strong bias in the comparative studies.
      For this reason, we have searched for identical sequences (99% of nucleotide
      identity) among these metagenomes in order to perform a reference-independent
      comparative analysis, and we were able to identify groups of microbial
      communities that may be under similar selective pressures. The identification of
      sequences shared among the metagenomes was found to be even better for the
      identification of groups of communities with similar niche requirements than the
      traditional analysis of functional profiles. This approach is not only helpful
      for the investigation of similarities between microbial communities with high
      proportion of unknown reads, but also enables an indirect overview of gene
      exchange between communities. 

PMID- 25379671
TI  - Asthma trajectories in early childhood: identifying modifiable factors.
AB  - BACKGROUND: There are conflicting views as to whether childhood wheezing
      represents several discreet entities or a single but variable disease.
      Classification has centered on phenotypes often derived using subjective
      criteria, small samples, and/or with little data for young children. This is
      particularly problematic as asthmatic features appear to be entrenched by age
      6/7. In this paper we aim to: identify longitudinal trajectories of wheeze and
      other atopic symptoms in early childhood; characterize the resulting trajectories
      by the socio-economic background of children; and identify potentially modifiable
      processes in infancy correlated with these trajectories. DATA AND METHODS: The
      Millennium Cohort Study is a large, representative birth cohort of British
      children born in 2000-2002. Our analytical sample includes 11,632 children with
      data on key variables (wheeze in the last year; ever hay-fever and/or eczema)
      reported by the main carers at age 3, 5 and 7 using a validated tool, the
      International Study of Asthma and Allergies in Childhood module. We employ
      longitudinal Latent Class Analysis, a clustering methodology which identifies
      classes underlying the observed population heterogeneity. RESULTS: Our model
      distinguished four latent trajectories: a trajectory with both low levels of
      wheeze and other atopic symptoms (54% of the sample); a trajectory with low
      levels of wheeze but high prevalence of other atopic symptoms (29%); a trajectory
      with high prevalence of both wheeze and other atopic symptoms (9%); and a
      trajectory with high levels of wheeze but low levels of other atopic symptoms
      (8%). These groups differed in terms of socio-economic markers and potential
      intervenable factors, including household damp and breastfeeding initiation.
      CONCLUSION: Using data-driven techniques, we derived four trajectories of
      asthmatic symptoms in early childhood in a large, population based sample. These
      groups differ in terms of their socio-economic profiles. We identified correlated
      intervenable pathways in infancy, including household damp and breastfeeding
      initiation.

PMID- 25379672
TI  - Identification of histological patterns in clinically affected and unaffected
      palm regions in dupuytren's disease.
AB  - Dupuytren's disease is a fibro-proliferative disease characterized by a disorder
      of the extracellular matrix (ECM) and high myofibroblast proliferation. However,
      studies failed to determine if the whole palm fascia is affected by the disease.
      The objective of this study was to analyze several components of the
      extracellular matrix of three types of tissues-Dupuytren's diseased contracture
      cords (DDC), palmar fascia clinically unaffected by Dupuytren's disease
      contracture (NPF), and normal forehand fascia (NFF). Histological analysis,
      quantification of cells recultured from each type of tissue, mRNA microarrays and
      immunohistochemistry for smooth muscle actin (SMA), fibrillar ECM components and
      non-fibrillar ECM components were carried out. The results showed that DDC
      samples had abundant fibrosis with reticular fibers and few elastic fibers, high
      cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did
      not show any of these findings. Interestingly, NPF tissues had more cells showing
      myofibroblasts differentiation and more collagen and reticular fibers, laminin
      and glycoproteins than NFF, although at lower level than DDC, with similar
      elastic fibers than DDC. Immunohistochemical expression of decorin was high in
      DDC, whereas versican was highly expressed NFF, with no differences for aggrecan.
      Cluster analysis revealed that the global expression profile of NPF was very
      similar to DDC, and reculturing methods showed that cells corresponding to DDC
      tissues proliferated more actively than NPF, and NPF more actively than NFF. All
      these results suggest that NPF tissues may be affected, and that a modification
      of the therapeutic approach used for the treatment of Dupuytren's disease should
      be considered. 

PMID- 25379673
TI  - A comparison between the EQ-5D and the SF-6D in patients with chronic obstructive
      pulmonary disease (COPD).
AB  - BACKGROUND: The appropriate use of generic preference-based measures determines
      the accuracy of disease assessment and further decision on healthcare policy
      using quality adjusted life years. The discriminative capacity of different
      instruments would differ across disease groups. Our study was to examine the
      difference in utility scores for COPD patients measured by EQ-5D and SF-6D and to
      assist the choice of a proper instrument in this disease group. METHODS:
      Differences of mean utility scores of EQ-5D and SF-6D in groups defined by socio
      demographic characteristics, comorbidities, health service utilisation and
      severity of illness were tested using Mann-Whitney test, t-test, Kruskal-Wallis
      test, Pearson's correlation coefficient and ANOVA, as appropriate. The
      discriminative properties of the two instruments were compared against indicators
      of quality of life using receiver operating characteristic curves. The
      statistical significance of the area under the curves (AUC) was tested by ANOVA
      and F-statistics used to compare the efficiency with which each instrument
      discriminated between disease severity groups. RESULTS: Mean utility scores of EQ
      5D and SF-6D were 0.644 and 0.629 respectively in the 154 subjects included in
      the analysis. EQ-5D scores were significantly higher than SF-6D in groups less
      severe and these differences corresponded to a minimally important difference of
      greater than 0.03 (p<0.001). EQ-5D and SF-6D scores were strongly correlated
      across the whole sample (r = 0.677, p<0.001) and in pre-defined groups (r>0.5 and
      p<0.05 for all correlation coefficients). AUCs were above 0.5 against the
      indicators of health-related quality of life for both instruments. F-ratios
      suggested SF-6D was more efficient in discriminating cases of different disease
      severity than EQ-5D. CONCLUSIONS: Both EQ-5D and SF-6D appeared to be valid
      preference-based measures in Chinese COPD patients. SF-6D was more efficient in
      detecting differences among subgroups with differing health status. EQ-5D and SF
      6D measured different things and might not be used interchangeably in COPD
      patients.

PMID- 25379674
TI  - Photoacoustic tomography of human hepatic malignancies using intraoperative
      indocyanine green fluorescence imaging.
AB  - Recently, fluorescence imaging following the preoperative intravenous injection
      of indocyanine green has been used in clinical settings to identify hepatic
      malignancies during surgery. The aim of this study was to evaluate the ability of
      photoacoustic tomography using indocyanine green as a contrast agent to produce
      representative fluorescence images of hepatic tumors by visualizing the spatial
      distribution of indocyanine green on ultrasonographic images. Indocyanine green
      (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing
      hepatectomy. Intraoperatively, photoacoustic tomography was performed on the
      surface of the resected hepatic specimens (n = 10) under excitation with an 800
      nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging
      identified indocyanine green accumulation in the cancerous tissue. In contrast,
      in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one
      intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic
      imaging delineated indocyanine green accumulation not in the cancerous tissue but
      rather in the peri-cancerous hepatic parenchyma. Although photoacoustic
      tomography enabled to visualize spatial distribution of ICG on ultrasonographic
      images, which was consistent with fluorescence images on cut surfaces of the
      resected specimens, photoacoustic signals of ICG-containing tissues decreased
      approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic
      tomography using indocyanine green also failed to identify any hepatocellular
      carcinoma nodules from the body surface of model mice with non-alcoholic
      steatohepatitis. In conclusion, photoacoustic tomography has a potential to
      enhance cancer detectability and differential diagnosis by ultrasonographic
      examinations and intraoperative fluorescence imaging through visualization of
      stasis of bile-excreting imaging agents in and/or around hepatic tumors. However,
      further technical advances are needed to improve the visibility of photoacoustic
      signals emitted from deeply-located lesions. 

PMID- 25379677
TI  - N-doped amorphous carbon coated Fe3O4/SnO2 coaxial nanofibers as a binder-free
      self-supported electrode for lithium ion batteries.
AB  - N-doped amorphous carbon coated Fe3O4/SnO2 coaxial nanofibers were prepared via a
      facile approach. The core composite nanofibers were first made by electrospinning
      technology, then the shells were conformally coated using the chemical bath
      deposition and subsequent carbonization with polydopamine as a carbon source.
      When applied as a binder-free self-supported anode for lithium ion batteries, the
      coaxial nanofibers displayed an enhanced electrochemical storage capacity and
      excellent rate performance. The morphology of the interwoven nanofibers was
      maintained even after the rate cycle test. The superior electrochemical
      performance originates in the structural stability of the N-doped amorphous
      carbon shells formed by carbonizing polydopamine. 

PMID- 25379676
TI  - Visualization of oxytocin release that mediates paired pulse facilitation in
      hypothalamic pathways to brainstem autonomic neurons.
AB  - Recent work has shown that oxytocin is involved in more than lactation and
      uterine contraction. The paraventricular nucleus of the hypothalamus (PVN)
      contains neuroendocrine neurons that control the release of hormones, including
      vasopressin and oxytocin. Other populations of PVN neurons do not release
      hormones, but rather project to and release neurotransmitters onto other neurons
      in the CNS involved in fluid retention, thermoregulation, sexual behavior and
      responses to stress. Activation of oxytocin receptors can be cardioprotective and
      reduces the adverse cardiovascular consequences of anxiety and stress, yet how
      oxytocin can affect heart rate and cardiac function is unknown. While anatomical
      work has shown the presence of peptides, including oxytocin, in the projections
      from the PVN to parasympathetic nuclei, electrophysiological studies to date have
      only demonstrated release of glutamate and activation of fast ligand gated
      receptors in these pathways. In this study, using rats, we directly show, using
      sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO,
      that optogenetic activation of channelrhodopsin-2 (ChR2) expressing PVN fibers in
      the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus
      (DMNV). We also demonstrate that while a single photoactivation of PVN terminals
      only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs),
      neurons that dominate the neural control of heart rate, both the paired pulse
      facilitation, and sustained enhancement of glutamate release in this pathway is
      mediated by activation of oxytocin receptors. Our results provide direct evidence
      that a pathway from the PVN likely releases oxytocin and enhances short-term
      plasticity of this critical autonomic connection. 

PMID- 25379678
TI  - Risk assessment of component failure modes and human errors using a new FMECA
      approach: application in the safety analysis of HDR brachytherapy.
AB  - Failure mode, effects and criticality analysis (FMECA) is a safety technique
      extensively used in many different industrial fields to identify and prevent
      potential failures. In the application of traditional FMECA, the risk priority
      number (RPN) is determined to rank the failure modes; however, the method has
      been criticised for having several weaknesses. Moreover, it is unable to
      adequately deal with human errors or negligence. In this paper, a new versatile
      fuzzy rule-based assessment model is proposed to evaluate the RPN index to rank
      both component failure and human error. The proposed methodology is applied to
      potential radiological over-exposure of patients during high-dose-rate
      brachytherapy treatments. The critical analysis of the results can provide
      recommendations and suggestions regarding safety provisions for the equipment and
      procedures required to reduce the occurrence of accidental events. 

PMID- 25379675
TI  - Is the readmission rate a valid quality indicator? A review of the evidence.
AB  - INTRODUCTION: Hospital readmission rates are increasingly used for both quality
      improvement and cost control. However, the validity of readmission rates as a
      measure of quality of hospital care is not evident. We aimed to give an overview
      of the different methodological aspects in the definition and measurement of
      readmission rates that need to be considered when interpreting readmission rates
      as a reflection of quality of care. METHODS: We conducted a systematic literature
      review, using the bibliographic databases Embase, Medline OvidSP, Web-of-Science,
      Cochrane central and PubMed for the period of January 2001 to May 2013. RESULTS:
      The search resulted in 102 included papers. We found that definition of the
      context in which readmissions are used as a quality indicator is crucial. This
      context includes the patient group and the specific aspects of care of which the
      quality is aimed to be assessed. Methodological flaws like unreliable data and
      insufficient case-mix correction may confound the comparison of readmission rates
      between hospitals. Another problem occurs when the basic distinction between
      planned and unplanned readmissions cannot be made. Finally, the multi-faceted
      nature of quality of care and the correlation between readmissions and other
      outcomes limit the indicator's validity. CONCLUSIONS: Although readmission rates
      are a promising quality indicator, several methodological concerns identified in
      this study need to be addressed, especially when the indicator is intended for
      accountability or pay for performance. We recommend investing resources in
      accurate data registration, improved indicator description, and bundling outcome
      measures to provide a more complete picture of hospital care.

PMID- 25379679
TI  - Active patient participation in the development of an online intervention.
AB  - BACKGROUND: An important and challenging part of living with cancer relates to
      the repeated visits to the hospital. Since how patients cope between these post
      diagnostic visits depends partly on the information and support received from
      their physician during the visits, it is important to make the most of them.
      Recent findings reinforce the importance of training not only the health care
      professionals in communication skills, but providing patients with support in
      communication as well. Delivering such supportive interventions online can have
      potential benefits in terms of accessibility, cost-effectiveness, and ability to
      tailor information to personal needs. However, problems with attrition (dropout,
      non-usage) during the test phase and poor uptake after implementation are
      frequently reported. The marginal level of engagement of the patient as end user
      seems to play a role in this. Therefore, recent research suggests integrating
      theory-based development methods with methods that promote involvement of the
      patient at an early stage. This paper describes a participatory protocol, used to
      let patients guide a theory-informed development process. OBJECTIVE: The
      objective of this project was to apply a bottom-up inspired procedure to develop
      a patient-centered intervention with corresponding evaluation and implementation
      plan. METHODS: The applied development protocol was based on the intervention
      mapping framework, combined with patient participatory methods that were inspired
      by the participation ladder and user-centred design methods. RESULTS: The applied
      protocol led to a self-directed online communication intervention aimed at
      helping patients gain control during their communications with health care
      professionals. It also led to an evaluation plan and an implementation plan. The
      protocol enabled the continuous involvement of patient research partners and the
      partial involvement of patient service users, which led to valuable insights and
      improvements. CONCLUSIONS: The applied protocol realized patient participation on
      different levels throughout the entire project. Early involvement, involvement on
      different levels, and flexibility in terms of planning and setup seem to be
      preconditions to creating a bottom-up inspired development procedure with
      (seriously ill) patients. Further research is necessary to find out if a more
      patient-centered approach improves the implementation and uptake of eHealth
      interventions. TRIAL REGISTRATION: Netherlands National Trial Register ID number:
      NTR3779; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3779 (Archived
      by WebCite at http://www.webcitation.org/6TdfALKxV).

PMID- 25379680
TI  - TiO2/ZnO inner/outer double-layer hollow fibers for improved detection of
      reducing gases.
AB  - TiO2/ZnO double-layer hollow fibers (DLHFs) are proposed as a superior sensor
      material in comparison to regular single-layer hollow fibers (HFs) for the
      detection of reducing gases. DLHFs were synthesized on sacrificial polymer fibers
      via atomic layer deposition of a first layer of TiO2 followed by a second layer
      of ZnO and by a final thermal treatment. The inner TiO2 receives electrons from
      the ZnO outer layer, which becomes more resistive due to the significant loss of
      electrons. This highly resistive ZnO layer partially regains its original
      resistivity when exposed to reducing gases such as CO, thus enabling more
      resistance variation in DLHFs. DLHFs are a novel material compared to HFs and can
      be successfully employed to fabricate chemical sensors for the accurate detection
      of reducing gases. 

PMID- 25379686
TI  - Spontaneous aryldiazonium film formation on 440C stainless steel in nonaqueous
      environments.
AB  - The ability of three aryldiazonium salts to spontaneously assemble onto the
      surface of type 440C stainless steel is investigated in acetonitrile (ACN) and
      the model hydraulic fluids tributyl phosphate (TBP) and hexamethyldisiloxane
      (HMDS). Competition between native oxide formation and organic film growth at
      different diazonium salt concentrations is monitored by electrochemical impedance
      spectroscopy. At 1 mM diazonium salt, 70% of total assembly is complete within 10
      min, though total surface coverage by organics is limited to ~0.15 monolayers.
      Adding HCl to the electrolyte renders native oxide formation unfavorable, yet the
      diazonium molecules are still unable to the increase surface coverage over 1 M-10
      MUM HCl in solution. X-ray photoelectron spectroscopy confirms preferential
      bonding of organic molecules to iron over chromium, while secondary ion mass
      spectroscopy reveals the ability of these films to self-heal when mechanically
      removed or damaged. Aging the diazonium salts in these nonaqueous environments
      demonstrates that up to 90% of the original diazonium salt concentration remains
      after 21 days at room temperature, while increasing the temperature beyond 50 
      degrees C results in complete decomposition within 24 h, regardless of solvent
      salt combination. It is concluded that the investigated diazonium molecules will
      not spontaneously form a continuous monolayer on 440C stainless steel immersed in
      ACN, TBP, or HMDS. 

PMID- 25379685
TI  - Assessing pulmonary hypertensive vascular disease in childhood. Data from the
      Spanish registry.
AB  - RATIONALE: There is a lack of knowledge regarding the epidemiology, clinical
      characterization, and survival in pediatric pulmonary hypertension. OBJECTIVES:
      To describe the epidemiology, outcomes, and risk factors for mortality in
      pediatric pulmonary hypertension in Spain. METHODS: We analyzed data from the
      Spanish Registry for Pediatric Pulmonary Hypertension. From January 2009 to June
      2012, a total of 225 patients diagnosed with pulmonary hypertension in 1998 or
      after were collected from 21 referral and nonreferral centers. We included all
      Nice etiologies, estimated incidence and prevalence of pulmonary hypertension in
      the Spanish pediatric population, and analyzed risk factors for mortality (Nice
      etiologic group, clinical and hemodynamic variables). Patients were classified as
      follows: group I, pulmonary arterial hypertension (n = 142; 61%); group II, left
      heart disease (n = 31; 14%); group III, respiratory disease (n = 41; 18%); group
      IV, thromboembolic pulmonary hypertension (n = 2; 1%); or group V, mostly
      inherited metabolic diseases (n = 10; 4.5%). Of the patients studied, 31% had
      multifactorial pulmonary hypertension. MEASUREMENTS AND MAIN RESULTS: Mean age at
      diagnosis was 4.3 +/- 4.9 years (50% < 2 yr). Survival rates at 1 and 3 years
      were 80 and 74% for the whole cohort, and 89 and 85% for patients with pulmonary
      arterial hypertension. Independent risk factors for mortality included an
      etiologic group other than pulmonary arterial hypertension (P < 0.001), age at
      diagnosis younger than 2 years old (P < 0.001), advanced functional class at
      diagnosis (P < 0.001), and high right atrial pressure at diagnosis (P = 0.002).
      CONCLUSIONS: In moderate to severe pediatric pulmonary hypertension, the
      prognosis is better in pulmonary arterial hypertension than in other Nice
      categories. In pediatric pulmonary hypertension age at diagnosis younger than 2
      years is a risk factor for mortality, in addition to the previously established
      risk factors.

PMID- 25379687
TI  - A coarse-grained simulation for tensile behavior of 2D Au nanocrystal
      superlattices.
AB  - We performed a coarse-grained. molecular dynamics (MD) simulation to study the
      unidirectional tension of 2D superlattices of alkythiol-ligated Au nanocrystals
      (NCs). Consistent with available experiments, the predicted Young's modulus is in
      the range of 6-15 GPa, exhibiting a trend of decreasing with the increasing NCs'
      size and decreasing ligand length. Our simulation shows that the deformation of
      the superlattice experiences elastic and nonelastic stages before defect
      nucleation at the NC level. The larger tensile strain gives rise to slips along
      the most densely packed lines, making them equal to [Formula: see text] with the
      tensile direction before deformation, which further triggers the occurrence of
      cavities and cracks and finally leads to the fracture of the specimen. These
      results provide a clear picture for the tensile behavior of 2D superlattices from
      deformation to rupture. 

PMID- 25379688
TI  - Antihypertensive potential of combined extracts of olive leaf, green coffee bean
      and beetroot: a randomized, double-blind, placebo-controlled crossover trial.
AB  - Extracts of olive leaf, green coffee bean and beetroot may deliver cardiovascular
      benefits. This study sought to evaluate the effects of regularly consuming a
      combination of these extracts on blood pressure (BP), arterial compliance, blood
      lipids, blood glucose and insulin sensitivity. A double-blind randomised placebo
      controlled crossover trial was conducted in adults with untreated high normal or
      borderline elevated BP. They were randomised to take an active supplement,
      comprising 500 mg olive leaf extract, 100 mg green coffee bean extract and 150 mg
      beet powder, or a matching placebo twice daily for six weeks, followed by the
      alternate supplement for a further six weeks. Assessments of 24-h ambulatory BP
      (ABP), clinic BP arterial compliance (pulse-wave analysis), blood lipids, blood
      glucose and insulin were obtained at baseline and at the end of each treatment
      phase. Baseline clinic BP in 37 overweight middle-aged men and women who
      completed the trial averaged 145/84 mmHg. There was no significant effect of
      treatment on ABP or any other outcome measure. The failure to confirm prior
      evidence of the antihypertensive benefits of these extracts emphasises the
      importance of placebo control and the value of ABP monitoring. Further dose
      response evaluation of olive leaf, green coffee bean or beetroot extracts is
      required to confirm or refute the purported benefits. 

PMID- 25379689
TI  - Gender differences in exercise dependence and eating disorders in young adults: a
      path analysis of a conceptual model.
AB  - The purpose of our study was to study the prevalence of exercise dependence (EXD)
      among college students and to investigate the role of EXD and gender on exercise
      behavior and eating disorders. Excessive exercise can become an addiction known
      as exercise dependence. In our population of 517 college students, 3.3% were at
      risk for EXD and 8% were at risk for an eating disorder. We used Path analysis
      the simplest case of Structural Equation Modeling (SEM) to investigate the role
      of EXD and exercise behavior on eating disorders. We observed a small direct
      effect from gender to eating disorders. In females we observed significant direct
      effect between exercise behavior (r = -0.17, p = 0.009) and EXD (r = 0.34, p <
      0.001) on eating pathology. We also observed an indirect effect of exercise
      behavior on eating pathology (r = 0.16) through EXD (r = 0.48, r2 = 0.23, p <
      0.001). In females the total variance of eating pathology explained by the SEM
      model was 9%. In males we observed a direct effect between EXD (r = 0.23, p <
      0.001) on eating pathology. We also observed indirect effect of exercise behavior
      on eating pathology (r = 0.11) through EXD (r = 0.49, r2 = 0.24, p < 0.001). In
      males the total variance of eating pathology explained by the SEM model was 5%. 

PMID- 25379690
TI  - [Health services research for the public health service (PHS) and the public
      health system].
AB  - INTRODUCTION: There is a great need for health services research in the public
      health system and in the German public health service. However, the public health
      service is underrepresented in health services research in Germany. This has
      several structural, historical and disciplinary-related reasons. The public
      health service is characterised by a broad range of activities, high
      qualification requirements and changing framework conditions. RESULTS: The
      concept of health services research is similar to that of the public health
      service and public health system, because it includes the principles of
      multidisciplinarity, multiprofessionalism and daily routine orientation. This
      article focuses on a specified system theory based model of health services
      research for the public health system and public health service. The model is
      based on established models of the health services research and health system
      research, which are further developed according to specific requirements of the
      public health service. It provides a theoretical foundation for health services
      research on the macro-, meso- and microlevels in public health service and the
      public health system. DISCUSSION: Prospects for public health service are seen in
      the development from "old public health" to "new public health" as well as in the
      integration of health services research and health system research. There is a
      significant potential for development in a better linkage between university
      research and public health service as is the case for the "Pettenkofer School of
      Public Health Munich".

PMID- 25379691
TI  - [Patient-centredness in health services research].
AB  - This paper provides a sketch of key research areas within health services
      research focusing on patient-centredness. The evaluation of patient-reported
      outcomes (PROs) is increasingly required for evaluating interventions in clinical
      trials and in routine health care. Often, however, it is un-clear which PROs are
      best suited for a particular research question. One of the most commonly used PRO
      is the construct of quality of life (QoL), which has become an established
      outcome in clinical trials and is also named as a health goal in the German
      Social Code of Law. The concept of patient empowerment implies that autonomy and
      room for manoeuver of the individual patient should be strengthened. However, it
      is un-clear how the concept is best operationalised. One prerequisite for patient
      empowerment in routine health care is the development and implementation of
      evidence-based patient information. Another prominent research area focuses on
      the role of self-help and patient organisations in health services. Topics of
      interest are aims and activities of self-help organisations, potentials and
      challenges of integrating self-help into professional health services, effects of
      organised self-help support on patients and barriers of use.

PMID- 25379692
TI  - Association of FK506 binding protein 5 (FKBP5) gene rs4713916 polymorphism with
      mood disorders: a meta-analysis.

PMID- 25379693
TI  - Dose-related effects of venlafaxine on pCREB and brain-derived neurotrophic
      factor (BDNF) in the hippocampus of the rat by chronic unpredictable stress.

PMID- 25379694
TI  - Multifocal visual-evoked potentials in patients with schizophrenia during
      treatment.

PMID- 25379695
TI  - p-Synephrine suppresses glucose production but not lipid accumulation in H4IIE
      liver cells.
AB  - p-Synephrine, the primary protoalkaloid in the extract of bitter orange and other
      citrus species, has gained interest due to its lipolytic activity in adipose
      tissues. We previously found that p-synephrine stimulates glucose consumption via
      AMP-activated protein kinase (AMPK) in L6 skeletal muscle cells. This study
      investigated the effect of p-synephrine on glucose production and lipid
      accumulation in H4IIE rat liver cells. Glucose production was increased in H4llE
      cells that were incubated in glucose-free medium but decreased dose dependently
      (1-100 MUM) with p-synephrine treatment. Protein levels of glucose-6-phosphatase
      (G6Pase) and phosphoenol pyruvate carboxykinase (PEPCK) were also decreased by
      treatment (4 h) with p-synephrine. Antagonists against alpha- and beta-adrenergic
      receptors (phentolamine and propranolol) and other inhibitors against signaling
      molecules did not interrupt p-synephrine-induced suppression in glucose
      production. However, H7 (an inhibitor of serine/threonine kinases PKA, PKC, and
      PKG) significantly blocked p-synephrine-induced suppression of glucose production
      and further increased basal glucose production. Unlike the suppressive effect on
      glucose production, p-synephrine failed to affect palmitic acid-induced
      cytoplasmic lipid accumulation. Protein levels of fatty acid synthase (FAS) and
      phosphorylation levels of AMPK and ACC were not changed by p-synephrine.
      Altogether, p-synephrine can suppress glucose production but does not affect
      lipid accumulation in H4IIE liver cells.

PMID- 25379696
TI  - Cue strength in second-language processing: an eye-tracking study.
AB  - This study used eye-tracking and grammaticality judgement measures to examine how
      second-language (L2) learners process syntactic violations in English.
      Participants were native Arabic and native Mandarin Chinese speakers studying
      English as an L2, and monolingual English-speaking controls. The violations
      involved incorrect word order and differed in two ways predicted to be important
      by the unified competition model [UCM; MacWhinney, B. (2005). A unified model of
      language acquisition. In J. F. Kroll & A. M. B. de Groot (Eds.), Handbook of
      bilingualism: Psycholinguistic approaches (pp. 49-67). Oxford: Oxford University
      Press.]. First, one violation had more and stronger cues to ungrammaticality than
      the other. Second, the grammaticality of these word orders varied in Arabic and
      Mandarin Chinese. Sensitivity to violations was relatively quick overall, across
      all groups. Sensitivity also was related to the number and strength of cues to
      ungrammaticality regardless of native language, which is consistent with the
      general principles of the UCM. However, there was little evidence of cross
      language transfer effects in either eye movements or grammaticality judgements. 

PMID- 25379697
TI  - Unique associations between anxiety, depression and motives for approach and
      avoidance goal pursuit.
AB  - This study investigated the shared and distinct associations between depressive
      and anxious symptoms and motives for pursuing personal goals. One hundred and
      thirty-six undergraduates generated approach and avoidance goals and rated each
      on intrinsic, identified, introjected and external motives. Anxious and
      depressive symptoms showed significant unique associations with distinct motives.
      Specifically, depressive symptoms predicted significant unique variance in
      intrinsic motivation for approach goals (but not avoidance goals), whereas
      anxious symptoms predicted significant unique variance in introjected regulation
      for approach and avoidance goals. Some of these findings were moderated by
      gender. The findings broadly support the notion that depression is uniquely
      characterised by reduced enjoyment of approach goal pursuit whereas anxiety is
      uniquely characterised by pursuit of goals in order to avoid negative outcomes.
      We suggest that these findings are compatible with regulatory focus theory and
      suggest that motives for goal pursuit are important in understanding the relation
      between goals and specific mood disorder symptoms. 

PMID- 25379698
TI  - Correlation between serum levels of IL-15 and IL-17 in patients with idiopathic
      inflammatory myopathies.
AB  - OBJECTIVES: To assess the serum levels of interleukin (IL)-15 and IL-17 in
      patients with idiopathic inflammatory myopathies (IIM) and correlate them with
      levels of IL-1 receptor antagonist (IL-1ra), IL-6, IL-10, interferon (IFN)-gamma,
      monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)
      1alpha, and MIP-1beta. Possible correlations with disease activity parameters
      were also evaluated. METHOD: Sera from 14 patients with new-onset polymyositis
      (PM), 10 with dermatomyositis (DM), seven with anti-synthetase syndrome (ASS) and
      19 healthy controls (HC) were analysed by multiplex immunoassay. Sera from 19
      patients were analysed after a median follow-up of 5 months. All patients
      underwent physical examination, manual muscle testing (MMT) using the five-point
      MMT scales, the Health Assessment Questionnaire (HAQ), and serum creatine kinase
      (CK) measurement. All patients received glucocorticoids, and 13 were taking
      immunosuppressive therapy. RESULTS: At baseline, serum levels of IL-15, IL-17,
      MCP-1, and MIP-1beta were significantly higher in IIM patients than in HC. IL-17
      serum levels were directly correlated (r = 0.39, p = 0.02) with disease duration
      while a significant inverse correlation was detected between IL-17 levels and MMT
      scores (r = -0.4, p = 0.02). The highest IL-15 levels were present in DM patients
      (p = 0.02 vs. PM). The most striking finding was the strong correlation between
      IL-15 and IL-17 levels (r = 0.60, p = 0.0001), and this correlation was even
      stronger in DM patients (r = 0.82, p = 0.006). CONCLUSIONS: The strong
      correlation between IL-15 and IL-17 in IIM patients, and especially in DM,
      suggests that there may be an interplay between the two cytokines in the
      pathogenesis of myositis. Further studies of larger patient cohorts and of muscle
      biopsies are needed to confirm these preliminary data.

PMID- 25379699
TI  - Enhancing of women functional status with metabolic syndrome by cardioprotective
      and anti-inflammatory effects of combined aerobic and resistance training.
AB  - These data describe the effects of combined aerobic plus resistance training (CT)
      with regards to risk factors of metabolic syndrome (MetS), quality of life,
      functional capacity, and pro- and anti-inflammatory cytokines in women with MetS.
      In this context, thirteen women (35.4 +/- 6.2 yr) completed 10 weeks of CT
      consisting of three weekly sessions of ~60 min aerobic training (treadmill at 65
      70% of reserve heart rate, 30 min) and resistance training (3 sets of 8-12
      repetitions maximum for main muscle groups). Dependent variables were maximum
      chest press strength; isometric hand-grip strength; 30 s chair stand test; six
      minute walk test; body mass; body mass index; body adiposity index; waist
      circumference; systolic (SBP), diastolic and mean blood pressure (MBP); blood
      glucose; HDL-C; triglycerides; interleukins (IL) 6, 10 and 12, osteoprotegerin
      (OPG) and serum nitric oxide metabolite (NOx); quality of life (SF-36) and Z
      Score of MetS. There was an improvement in muscle strength on chest press (p =
      0.009), isometric hand-grip strength (p = 0.03) and 30 s chair stand (p = 0.007).
      There was a decrease in SBP (p = 0.049), MBP (p = 0.041), Z-Score of MetS (p =
      0.046), OPG (0.42 +/- 0.26 to 0.38 +/- 0.19 ng/mL, p<0.05) and NOx (13.3 +/- 2.3
      umol/L to 9.1 +/- 2.3 umol/L; p<0.0005). IL-10 displayed an increase (13.6 +/-
      7.5 to 17.2 +/- 12.3 pg/mL, p < 0.05) after 10 weeks of training. Combined
      training also increased the perception of physical capacity (p = 0.011). This
      study endorses CT as an efficient tool to improve blood pressure, functional
      capacity, quality of life and reduce blood markers of inflammation, which has a
      clinical relevance in the prevention and treatment of MetS.

PMID- 25379701
TI  - Optimal Futility Interim Design: A Predictive Probability of Success Approach
      with Time-to-Event Endpoint.
AB  - An analytical way to compute predictive probability of success (PPOS) together
      with credible interval at interim analysis (IA) is developed for big clinical
      trials with time-to-event endpoints. The method takes account of the fixed data
      up to IA, the amount of uncertainty in future data, and uncertainty about
      parameters. Predictive power is a special type of PPOS. The result is confirmed
      by simulation. An optimal design is proposed by finding optimal combination of
      analysis time and futility cutoff based on some PPOS criteria. 

PMID- 25379700
TI  - Characterization of flower-bud transcriptome and development of genic SSR markers
      in Asian lotus (Nelumbo nucifera Gaertn.).
AB  - BACKGROUND: Asian lotus (Nelumbo nucifera Gaertn.) is the national flower of
      India, Vietnam, and one of the top ten traditional Chinese flowers. Although
      lotus is highly valued for its ornamental, economic and cultural uses, genomic
      information, particularly the expressed sequence based (genic) markers is
      limited. High-throughput transcriptome sequencing provides large amounts of
      transcriptome data for promoting gene discovery and development of molecular
      markers. RESULTS: In this study, 68,593 unigenes were assembled from 1.34 million
      454 GS-FLX sequence reads of a mixed flower-bud cDNA pool derived from three
      accessions of N. nucifera. A total of 5,226 SSR loci were identified, and 3,059
      primer pairs were designed for marker development. Di-nucleotide repeat motifs
      were the most abundant type identified with a frequency of 65.2%, followed by tri
      (31.7%), tetra- (2.1%), penta- (0.5%) and hexa-nucleotide repeats (0.5%). A
      total of 575 primer pairs were synthesized, of which 514 (89.4%) yielded PCR
      amplification products. In eight Nelumbo accessions, 109 markers were
      polymorphic. They were used to genotype a sample of 44 accessions representing
      diverse wild and cultivated genotypes of Nelumbo. The number of alleles per locus
      varied from 2 to 9 alleles and the polymorphism information content values ranged
      from 0.6 to 0.9. We performed genetic diversity analysis using 109 polymorphic
      markers. A UPGMA dendrogram was constructed based on Jaccard's similarity
      coefficients revealing distinct clusters among the 44 accessions. CONCLUSIONS:
      Deep transcriptome sequencing of lotus flower buds developed 3,059 genic SSRs,
      making a significant addition to the existing SSR markers in lotus. Among them,
      109 polymorphic markers were successfully validated in 44 accessions of Nelumbo.
      This comprehensive set of genic SSR markers developed in our study will
      facilitate analyses of genetic diversity, construction of linkage maps, gene
      mapping, and marker-assisted selection breeding for lotus.

PMID- 25379702
TI  - Posterior Precortical Vitreous Pocket in Children.
AB  - PURPOSE: The purpose of the present study was to investigate the profile of
      posterior precortical vitreous pocket (PPVP) in children using spectral-domain
      optical coherence tomography (OCT) and to compare the profile with that of
      adults. MATERIALS AND METHODS: In this retrospective comparative study, the
      height at the fovea and the horizontal diameter of PPVP in healthy children and
      adults in the upright position were measured based on OCT (Spectralis, Heidelberg
      Engineering GmbH, Heidelberg, Germany) images. PPVP diameter was divided into
      nasal length and temporal length based on the center of the fovea. The proportion
      of temporal length to the entire horizontal diameter was calculated as temporal
      length/horizontal diameter of PPVP. The association of age with the height and
      the proportion of temporal length to the entire horizontal diameter were
      evaluated in each group. The two values were also compared between the two
      groups. RESULTS: Sixty-three eyes of 63 children (mean age: 6.9 +/- 1.8 years)
      and 44 eyes of 44 young adults (mean age: 32.1 +/- 5.3 years) were included. The
      height of PPVP at the fovea was 355.3 +/- 80.3 um in children and 367.8 +/- 75.6
      um in adults. The proportion of temporal length to the entire horizontal diameter
      was 0.45 +/- 0.05 and 0.50 +/- 0.03. The proportion was significantly greater in
      adults than in children (p < 0.001), whereas the height (p = 0.349) was not
      different between the two groups. In children, there was a positive association
      between the age and the proportion of temporal length to the entire horizontal
      diameter (p = 0.001). CONCLUSION: The results suggest a progressive temporal
      extension of PPVP during childhood.

PMID- 25379703
TI  - miR-18a inhibits CDC42 and plays a tumour suppressor role in colorectal cancer
      cells.
AB  - The miR-17-92 cluster of microRNAs is elevated in colorectal cancer, and has a
      causative role in cancer development. Of the six miR-17-92 cluster members, miR
      19a and b in particular are key promoters of cancer development and cell
      proliferation, while preliminary evidence suggests that miR-18a may act in
      opposition to other cluster members to decrease cell proliferation. It was
      hypothesised that miR-18a may have a homeostatic function in helping to contain
      the oncogenic effect of the entire miR-17-92 cluster, and that elevated miR-17-92
      cluster activity without a corresponding increase in miR-18a may promote
      colorectal tumour progression. In colorectal cancer samples and corresponding
      normal colorectal mucosa, miR-18a displayed lower overall expression than other
      miR-17-92 cluster members. miR-18a was shown to have an opposing role to other
      miR-17-92 cluster members, in particular the key oncogenic miRNAs, miR-19a and b.
      Transfection of HCT116 and LIM1215 colorectal cancer cell lines with miR-18a
      mimics decreased proliferation, while a miR-18a inhibitor increased
      proliferation. miR-18a was also responsible for decreasing cell migration,
      altering cell morphology, inducing G1/S phase cell cycle arrest, increasing
      apoptosis, and enhancing the action of a pro-apoptotic agent. CDC42, a mediator
      of the PI3K pathway, was identified as a novel miR-18a target. Overexpression of
      miR-18a reduced CDC42 expression, and a luciferase assay confirmed that miR-18a
      directly targets the 3'UTR of CDC42. miR-18a mimics had a similar effect on
      proliferation as a small molecule inhibitor of CDC42. Inhibition of CDC42
      expression is likely to be a key mechanism by which miR-18a impairs cancer cell
      growth, with a target protector experiment revealing miR-18a influences
      proliferation via direct inhibition of CDC42. Inhibition of CCND1 by miR-18a may
      also assist in this growth-suppression effect. The homeostatic function of miR
      18a within the miR-17-92 cluster in colorectal cancer cells may be achieved
      through suppression of CDC42 and the PI3K pathway. 

PMID- 25379704
TI  - Clinical and molecular epidemiology of haemophilus influenzae causing invasive
      disease in adult patients.
AB  - OBJECTIVES: The epidemiology of invasive Haemophilus influenzae (Hi) has changed
      since the introduction of the Hi type b (Hib) vaccine. The aim of this study was
      to analyze the clinical and molecular epidemiology of Hi invasive disease in
      adults. METHODS: Clinical data of the 82 patients with Hi invasive infections
      were analyzed. Antimicrobial susceptibility, serotyping, and genotyping were
      studied (2008-2013). RESULTS: Men accounted for 63.4% of patients (whose mean age
      was 64.3 years). The most frequent comorbidities were immunosuppressive therapy
      (34.1%), malignancy (31.7%), diabetes, and COPD (both 22%). The 30-day mortality
      rate was 20.7%. The majority of the strains (84.3%) were nontypeable (NTHi) and
      serotype f was the most prevalent serotype in the capsulated strains. The highest
      antimicrobial resistance was for cotrimoxazole (27.1%) and ampicillin (14.3%).
      Twenty-three isolates (32.9%) had amino acid changes in the PBP3 involved in
      resistance. Capsulated strains were clonal and belonged to clonal complexes 6
      (serotype b), 124 (serotype f), and 18 (serotype e), whereas NTHi were
      genetically diverse. CONCLUSIONS: Invasive Hi disease occurred mainly in elderly
      and those with underlying conditions, and it was associated with a high mortality
      rate. NTHi were the most common cause of invasive disease and showed high genetic
      diversity.

PMID- 25379705
TI  - Unsupervised deconvolution of dynamic imaging reveals intratumor vascular
      heterogeneity and repopulation dynamics.
AB  - With the existence of biologically distinctive malignant cells originated within
      the same tumor, intratumor functional heterogeneity is present in many cancers
      and is often manifested by the intermingled vascular compartments with distinct
      pharmacokinetics. However, intratumor vascular heterogeneity cannot be resolved
      directly by most in vivo dynamic imaging. We developed multi-tissue compartment
      modeling (MTCM), a completely unsupervised method of deconvoluting dynamic
      imaging series from heterogeneous tumors that can improve vascular
      characterization in many biological contexts. Applying MTCM to dynamic contrast
      enhanced magnetic resonance imaging of breast cancers revealed characteristic
      intratumor vascular heterogeneity and therapeutic responses that were otherwise
      undetectable. MTCM is readily applicable to other dynamic imaging modalities for
      studying intratumor functional and phenotypic heterogeneity, together with a
      variety of foreseeable applications in the clinic. 

PMID- 25379706
TI  - Expression of the p53 target Wig-1 is associated with HPV status and patient
      survival in cervical carcinoma.
AB  - The p53 target gene WIG-1 (ZMAT3) is located in chromosomal region 3q26, that is
      frequently amplified in human tumors, including cervical cancer. We have examined
      the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell
      lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca
      Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype,
      comparative genomic hybridization and Southern blotting revealed WIG-1 is not the
      primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily
      expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical
      cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1
      expression by immunohistochemistry in 38 cervical tumor samples. We found higher
      nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p
      = 0.002) and in adenocarcinomas as compared to squamous cell lesions (p<0.0001).
      Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1
      staining showed longer survival than patients with strong nuclear and negative
      cytoplasmic staining (p = 0.042). Nuclear Wig-1 expression levels were positively
      associated with age at diagnosis (p = 0.023) and histologic grade (p = 0.034).
      These results are consistent with a growth-promoting and/or anti-cell death
      function of nuclear Wig-1 and suggest that Wig-1 expression can serve as a
      prognostic marker in cervical carcinoma.

PMID- 25379708
TI  - Iodide protects heart tissue from reperfusion injury.
AB  - Iodine is an elemental nutrient that is essential for mammals. Here we provide
      evidence for an acute therapeutic role for iodine in ischemia reperfusion injury.
      Infusion of the reduced form, iodide, but not the oxidized form iodate, reduces
      heart damage by as much as 75% when delivered intravenously following temporary
      loss of blood flow but prior to reperfusion of the heart in a mouse model of
      acute myocardial infarction. Normal thyroid function may be required because loss
      of thyroid activity abrogates the iodide benefit. Given the high degree of
      protection and the high degree of safety, iodide should be explored further as a
      therapy for reperfusion injury. 

PMID- 25379709
TI  - ISAAC position statement on facilitated communication. International Society for
      Augmentative and Alternative Communication.

PMID- 25379707
TI  - Modulation of gene expression by 3-iodothyronamine: genetic evidence for a
      lipolytic pattern.
AB  - 3-Iodothyronamine (T1AM) is an endogenous biogenic amine, structurally related to
      thyroid hormone, which is regarded as a novel chemical messenger. The molecular
      mechanisms underlying T1AM effects are not known, but it is possible to envisage
      changes in gene expression, since delayed and long-lasting phenotypic effects
      have been reported, particularly with regard to the modulation of lipid
      metabolism and body weight. To test this hypothesis we analysed gene expression
      profiles in adipose tissue and liver of eight rats chronically treated with T1AM
      (10 mg/Kg twice a day for five days) as compared with eight untreated rats. In
      vivo T1AM administration produced significant transcriptional effects, since 378
      genes were differentially expressed in adipose tissue, and 114 in liver. The
      reported changes in gene expression are expected to stimulate lipolysis and beta
      oxidation, while inhibiting adipogenesis. T1AM also influenced the expression of
      several genes linked to lipoprotein metabolism suggesting that it may play an
      important role in the regulation of cholesterol homeostasis. No effect on the
      expression of genes linked to toxicity was observed. The assay of tissue T1AM
      showed that in treated animals its endogenous concentration increased by about
      one order of magnitude, without significant changes in tissue thyroid hormone
      concentration. Therefore, the effects that we observed might have physiological
      or pathophysiological importance. Our results provide the basis for the reported
      effectiveness of T1AM as a lipolytic agent and gain importance in view of a
      possible clinical use of T1AM in obesity and/or dyslipidaemia. 

PMID- 25379712
TI  - Anti-ulcerogenic effect of methanolic extracts from Enicosanthellum pulchrum
      (King) Heusden against ethanol-induced acute gastric lesion in animal models.
AB  - A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which
      belongs to the family Annonaceae. In this study, methanol extract from the leaves
      and stems of this species was evaluated for its gastroprotective potential
      against mucosal lesions induced by ethanol in rats. Seven groups of rats were
      assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was
      administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups
      received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively.
      After an additional hour, the rats in groups 2-7 received ethanol (95% v/v; 8
      mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were
      sacrificed after 1 h and their stomachs subjected to further studies.
      Macroscopically and histologically, group 2 rats showed extremely severe
      disruption of the gastric mucosa compared to rats pre-treated with the E.
      pulchrum extracts based on the ulcer index, where remarkable protection was
      noticed. Meanwhile, a significant percentage of inhibition was shown with the
      stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with
      the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An
      increase in mucus content, nitric oxide, glutathione, prostaglandin E2,
      superoxide dismutase, protein and catalase, and a decrease in malondialdehyde
      level compared to group 2 were also obtained. Furthermore, immunohistochemical
      staining of groups 4-7 exhibited down-regulation of Bax and up-regulation of
      Hsp70 proteins. The methanol extract from the leaves and the stems showed notable
      gastroprotective potential against ethanol. 

PMID- 25379713
TI  - Neural mechanisms underlying the computation of hierarchical tree structures in
      mathematics.
AB  - Whether mathematical and linguistic processes share the same neural mechanisms
      has been a matter of controversy. By examining various sentence structures, we
      recently demonstrated that activations in the left inferior frontal gyrus (L.
      IFG) and left supramarginal gyrus (L. SMG) were modulated by the Degree of Merger
      (DoM), a measure for the complexity of tree structures. In the present study, we
      hypothesize that the DoM is also critical in mathematical calculations, and
      clarify whether the DoM in the hierarchical tree structures modulates activations
      in these regions. We tested an arithmetic task that involved linear and quadratic
      sequences with recursive computation. Using functional magnetic resonance
      imaging, we found significant activation in the L. IFG, L. SMG, bilateral
      intraparietal sulcus (IPS), and precuneus selectively among the tested
      conditions. We also confirmed that activations in the L. IFG and L. SMG were free
      from memory-related factors, and that activations in the bilateral IPS and
      precuneus were independent from other possible factors. Moreover, by fitting
      parametric models of eight factors, we found that the model of DoM in the
      hierarchical tree structures was the best to explain the modulation of
      activations in these five regions. Using dynamic causal modeling, we showed that
      the model with a modulatory effect for the connection from the L. IPS to the L.
      IFG, and with driving inputs into the L. IFG, was highly probable. The intrinsic,
      i.e., task-independent, connection from the L. IFG to the L. IPS, as well as that
      from the L. IPS to the R. IPS, would provide a feedforward signal, together with
      negative feedback connections. We indicate that mathematics and language share
      the network of the L. IFG and L. IPS/SMG for the computation of hierarchical tree
      structures, and that mathematics recruits the additional network of the L. IPS
      and R. IPS. 

PMID- 25379715
TI  - The first cytogenetic data on Strumigenys louisianae Roger, 1863 (Formicidae:
      Myrmicinae: Dacetini): the lowest chromosome number in the Hymenoptera of the
      neotropical region.
AB  - In the present study, the first cytogenetic data was obtained for the ant species
      Strumigenys louisianae, from a genus possessing no previous cytogenetic data for
      the Neotropical region. The chromosome number observed was 2n = 4, all possessing
      metacentric morphology. Blocks rich in GC base pairs were observed in the
      interstitial region of the short arm of the largest chromosome pair, which may
      indicate that this region corresponds to the NORs. The referred species presented
      the lowest chromosome number observed for the subfamily Myrmicinae and for the
      Hymenoptera found in the Neotropical region. Observation of a low chromosome
      number karyotype has been described in Myrmecia croslandi, in which the
      occurrence of tandem fusions accounts for the most probable rearrangement for its
      formation. The accumulation of cytogenetic data may carry crucial information to
      ensure deeper understanding of the systematics of the tribe Dacetini.

PMID- 25379714
TI  - Protective ventilation of preterm lambs exposed to acute chorioamnionitis does
      not reduce ventilation-induced lung or brain injury.
AB  - BACKGROUND: The onset of mechanical ventilation is a critical time for the
      initiation of cerebral white matter (WM) injury in preterm neonates, particularly
      if they are inadvertently exposed to high tidal volumes (VT) in the delivery
      room. Protective ventilation strategies at birth reduce ventilation-induced lung
      and brain inflammation and injury, however its efficacy in a compromised newborn
      is not known. Chorioamnionitis is a common antecedent of preterm birth, and
      increases the risk and severity of WM injury. We investigated the effects of high
      VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and
      injury, and whether a protective ventilation strategy could mitigate the
      response. METHODS: Pregnant ewes (n = 18) received intra-amniotic
      lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation
      at 127+/-1 days gestation. Lambs were either immediately euthanased and used as
      unventilated controls (LPSUVC; n = 6), or were ventilated using an injurious high
      VT strategy (LPSINJ; n = 5) or a protective ventilation strategy (LPSPROT; n = 7)
      for a total of 90 min. Mean arterial pressure, heart rate and cerebral
      haemodynamics and oxygenation were measured continuously. Lungs and brains
      underwent molecular and histological assessment of inflammation and injury.
      RESULTS: LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation
      requirements and cardiopulmonary and systemic haemodynamics were not different
      between ventilation strategies. Compared to unventilated lambs, LPSINJ and
      LPSPROT lambs had increases in pro-inflammatory cytokine expression within the
      lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in
      the WM, which were equivalent in magnitude between groups. CONCLUSIONS:
      Ventilation after acute chorioamnionitis, irrespective of strategy used,
      increases haemodynamic instability and lung and cerebral inflammation and injury.
      Mechanical ventilation is a potential contributor to WM injury in infants exposed
      to chorioamnionitis.

PMID- 25379716
TI  - Cryptogenic ischemic stroke and prevalence of asymptomatic atrial fibrillation: a
      prospective study.
AB  - BACKGROUND: Atrial fibrillation is responsible for up to one-third of ischemic
      strokes, and is also associated with silent cerebral infarctions and transient
      ischemic attacks (TIAs). The self-terminating and often asymptomatic nature of
      paroxysmal atrial fibrillation (PAF) may lead to its underdiagnosis. A continuous
      and long-term heart rhythm monitoring can be useful in unmasking PAF episodes.
      OBJECTIVE: Prevalence of asymptomatic PAF in patients suffering a cryptogenic
      stroke, at risk for atrial fibrillation but without any history of arrhythmia or
      palpitations, using a continuous electrocardiographic monitoring. METHODS: One
      hundred and forty-two consecutive patients were admitted to the Stroke Unit of
      'Citta della Salute e della Scienza' Hospital of Turin between June 2010 and
      March 2013 and discharged with the diagnosis of ischemic cryptogenic stroke.
      Sixty fulfilled predefined inclusion criteria. Follow-up was carried on and
      completed for the 54 patients who consented to implantable loop recorder (ILR)
      implantation. After ILR implantation, trans-telephonic data were collected
      monthly. RESULTS: Atrial fibrillation episodes lasting more than 5 min were
      recorded in 25 patients (46%), median detection time was 5.4 months (range 1-18)
      and median duration of atrial fibrillation episodes was 20 h (range 7 min-8 days)
      with 19 patients (76%) remaining asymptomatic and the others experiencing
      weakness and dyspnoea but not palpitations. CONCLUSION: Long-term heart rhythm
      monitoring is successful in unmasking silent atrial fibrillation in 46% of
      patients suffering a cryptogenic stroke with concomitant atrial fibrillation risk
      factors, but without history of arrhythmia or palpitations.

PMID- 25379717
TI  - Late constrictive pericarditis after surgical thymectomy: multimodal imaging.

PMID- 25379718
TI  - Coronary vasospasm complicated by ventricular fibrillation: arrhythmogenic
      morphological substrates detected in vivo by cardiac magnetic resonance.

PMID- 25379719
TI  - Low-density lipoprotein cholesterol lowering therapies: what is on the horizon?
AB  - Elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with
      an increased risk for cardiovascular disease (CVD). Statins have been the
      cornerstone of lipid therapy to lower LDL-C for the past two decades, but despite
      significant clinical efficacy in a majority of patients, a large residual risk
      remains for the development of initial or recurrent atherosclerotic CVD. In
      addition, owing to the side-effects, a significant percentage of patients cannot
      tolerate any statin dose or a high enough statin dose. Thus, novel therapeutic
      agents are currently being developed to lower LDL-C levels further. This review
      will highlight these novel therapeutic agents including antisense
      oligonucleotides focused on apolipoprotein B, proprotein convertase
      subtilisin/kexin type 9 (PCSK9) inhibitors, and microsomal triglyceride transfer
      protein inhibitors. For each therapeutic class, an overview of mechanism of
      action, pharmacokinetic data, and efficacy/safety evidence will be discussed. 

PMID- 25379720
TI  - Copy number variability analysis of pharmacogenes in patients with lymphoma,
      leukemia, hepatocellular, and lung carcinoma using The Cancer Genome Atlas data.
AB  - OBJECTIVE: Individual differences in drug efficacy and toxicity remain an
      important clinical concern. We investigated copy number variation (CNV)
      frequencies for pharmacogenes using The Cancer Genome Atlas dataset. MATERIALS
      AND METHODS: One hundred and fifty-two pharmacogenes were selected from liver
      hepatocellular carcinoma, lung squamous cell carcinoma (LUSC), acute myeloid
      leukemia, and lymphoid neoplasm diffuse large B-cell lymphoma (DLBL). The germ
      line and somatic CNV frequencies were analyzed. RESULTS: We found CNVs with more
      than 1% frequency in drug-metabolizing enzymes including CYP2A6, CYP2D6, GSTP1,
      CYP2E1, GSTM1, GSTT1, and SULT1A1, drug transporters such as SLC19A1 and SLC28A1,
      and targets such as FHIT in normal tissue or blood. GSTM1 had the highest
      frequency for gene gain (45.45, 39.18, 31.01, and 34.77%, respectively) and for
      gene loss (18.18, 29.38, 20.89, and 26.68%, respectively) in DLBL, acute myeloid
      leukemia, liver hepatocellular carcinoma, and LUSC. P2RY12 and P2RY1 had the
      highest frequency for gene gain in LUSC (26.95 and 26.68%, respectively) whereas
      ABCB1 and ABL2 had the highest frequency for gene gain in DLBL (27.27%) in cancer
      tissue or blood. CONCLUSION: Germ line and somatic CNVs of pharmacogenes may play
      a role in determining individual variations in drug responses. Inclusion of CNVs
      in pharmacogenetic variations holds promise as biomarkers that can increase the
      benefits and reduce the risks of drug therapy on an individual level.

PMID- 25379721
TI  - Genetic variants within obesity-related genes are associated with tumor
      recurrence in patients with stages II/III colon cancer.
AB  - OBJECTIVE: Obesity is an established risk factor for colorectal cancer (CRC)
      incidence and it is also linked to CRC recurrence and survival. Polymorphisms
      located in obesity-related genes are associated with an increased risk of
      developing several cancer types including CRC. We evaluated whether single
      nucleotide polymorphisms in obesity-related genes may predict tumor recurrence in
      colon cancer patients. MATERIALS AND METHODS: Genotypes were obtained from
      germline DNA from 207 patients with stage II or III colon cancer at the Norris
      Comprehensive Cancer Center. Nine polymorphisms in eight obesity-related genes
      (PPAR, LEP, NFKB, CD36, DRG1, NGAL, REGIA, and DSCR1) were evaluated. The primary
      endpoint of the study was the 3-year recurrence rate. Positive associations were
      also tested in an independent Japanese cohort of 350 stage III CRC patients.
      RESULTS: In univariate analysis, for PPARrs1801282, patients with a CC genotype
      had significantly lower recurrence probability (29 +/- 4% SE) compared with
      patients with a CG genotype (48 +/- 8% SE) [hazard ratio (HR): 1.77; 95%
      confidence interval (CI), 1.01-3.10; P = 0.040]. For DSCR1rs6517239, patients
      with an AA genotype had higher recurrence probability than patients carrying at
      least one allele G (37 +/- 4% SE vs. 15 +/- 6% SE) (HR: 0.51; 95% CI, 0.27-0.94;
      P = 0.027). This association was stronger in the patients bearing a left-sided
      tumor (HR: 0.34; 95% CI, 0.13-0.88; P = 0.018). In the Japanese cohort, no
      associations were found. CONCLUSION: This hypothesis-generating study suggests a
      potential influence of polymorphisms within obesity-related genes in the
      recurrence probability of colon cancer. These interesting results should be
      evaluated further.

PMID- 25379722
TI  - Function-impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify
      the therapeutic efficacy of statins in a population-based cohort.
AB  - BACKGROUND: The efficacy of statins, which are used commonly in primary and
      secondary prevention of cardiovascular diseases, shows a wide range of
      interindividual variability. Genetic variants of OATP1B1, a hepatic uptake
      transporter, can modify access of statins to its therapeutic target, thereby
      potentially altering drug efficacy. We studied the impact of genetic variants of
      OATP1B1 on the lipid-lowering efficacy of statins in a population-based setting.
      MATERIALS AND METHODS: The basis of the analysis was the Study of Health in
      Pomerania, a cohort of 2732 men and women aged 20-81 years. Included in the
      statistical analysis to evaluate the impact of OATP1B1 on therapeutic efficacy of
      statins were 214 individuals diagnosed with dyslipidaemia during initial
      recruitment and receiving statins during the 5-year follow-up. RESULTS: Analysing
      the impact of the OATP1B1 genotype, we observed a trend for lower statin-induced
      total cholesterol reduction in carriers of the SLCO1B1 512C variant. Restricting
      the analysis to patients receiving simvastatin, pravastatin, lovastatin and
      fluvastatin indicated a statistically significant association of the OATP1B1
      genotype on lipid parameters at the 5-year follow-up. No such effect was observed
      for atorvastatin. Calculation of achievement of treatment goals according to the
      NCEP-ATPIII guidelines showed a lower rate of successful treatment when
      harbouring the mutant allele for patients taking simvastatin (46.7 vs. 73.9%). A
      similar trend was observed for pravastatin (34.4 vs. 70.4%). CONCLUSION: Genetic
      variants of OATP1B1 leading to impaired hepatic uptake of statins translated into
      reduced drug efficacy in a population-based cohort.

PMID- 25379723
TI  - National trends in main causes of hospitalization: a multi-cohort register study
      of the finnish working-age population, 1976-2010.
AB  - BACKGROUND: The health transition theory argues that societal changes produce
      proportional changes in causes of disability and death. The aim of this study was
      to identify long-term changes in main causes of hospitalization in working-age
      population within a nation that has experienced considerable societal change.
      METHODOLOGY: National trends in all-cause hospitalization and hospitalizations
      for the five main diagnostic categories were investigated in the data obtained
      from the Finnish Hospital Discharge Register. The seven-cohort sample covered the
      period from 1976 to 2010 and consisted of 3,769,356 randomly selected Finnish
      residents, each cohort representing 25% sample of population aged 18 to 64 years.
      PRINCIPAL FINDINGS: Over the period of 35 years, the risk of hospitalization for
      cardiovascular diseases and respiratory diseases decreased. Hospitalization for
      musculoskeletal diseases increased whereas mental and behavioral hospitalizations
      slightly decreased. The risk of cancer hospitalization decreased marginally in
      men, whereas in women an upward trend was observed. CONCLUSIONS/SIGNIFICANCE: A
      considerable health transition related to hospitalizations and a shift in the
      utilization of health care services of working-age men and women took place in
      Finland between 1976 and 2010.

PMID- 25379724
TI  - No evidence for the association between a polymorphism in the PCLO depression
      candidate gene with memory bias in remitted depressed patients and healthy
      individuals.
AB  - The PCLO rs2522833 candidate polymorphism for depression has been associated to
      monoaminergic neurotransmission. In healthy and currently depressed individuals,
      the polymorphism has been found to affect activation of brain areas during memory
      processing, but no direct association of PCLO with memory bias was found. We
      hypothesized that the absence of this association might have been obscured by
      current depressive symptoms or genetically driven individual differences in
      reactivity to stressful events. Experiencing stressful childhood events fosters
      dysfunctional assumptions that are related to cognitive biases, and may modulate
      the predisposition for depression via epigenetic effects. The association between
      PCLO and memory bias, as well as interaction between PCLO and childhood events
      was studied in patients remitted from depression (N = 299), as well as a sample
      of healthy individuals (N = 157). The participants performed an emotional verbal
      memory task after a sad mood induction. Childhood trauma and adversity were
      measured with a questionnaire. The Genotype main effect, and Genotype by
      Childhood Events interaction were analyzed for memory bias in both samples. PCLO
      risk allele carrying remitted depressed patients did not show more negatively
      biased memory than non-risk allele carriers, not even patients with stressful
      childhood events. A similar pattern of results was found in healthy individuals.
      Memory bias may not be strongly associated with the PCLO rs2522833 polymorphism.
      We did not find any support for the PCLO-childhood events interaction, but the
      power of our study was insufficient to exclude this possibility. 

PMID- 25379725
TI  - The complex biogeography of the plant pathogen Xylella fastidiosa: genetic
      evidence of introductions and Subspecific introgression in Central America.
AB  - The bacterium Xylella fastidiosa is a plant pathogen with a history of
      economically damaging introductions of subspecies to regions where its other
      subspecies are native. Genetic evidence is presented demonstrating the
      introduction of two new taxa into Central America and their introgression into
      the native subspecies, X. fastidiosa subsp. fastidiosa. The data are from 10
      genetic outliers detected by multilocus sequence typing (MLST) of isolates from
      Costa Rica. Six (five from oleander, one from coffee) defined a new sequence type
      (ST53) that carried alleles at six of the eight loci sequenced (five of the seven
      MLST loci) diagnostic of the South American subspecies Xylella fastidiosa subsp.
      pauca which causes two economically damaging plant diseases, citrus variegated
      chlorosis and coffee leaf scorch. The two remaining loci of ST53 carried alleles
      from what appears to be a new South American form of X. fastidiosa. Four
      isolates, classified as X. fastidiosa subsp. fastidiosa, showed a low level of
      introgression of non-native DNA. One grapevine isolate showed introgression of an
      allele from X. fastidiosa subsp. pauca while the other three (from citrus and
      coffee) showed introgression of an allele with similar ancestry to the alleles of
      unknown origin in ST53. The presence of X. fastidiosa subsp. pauca in Central
      America is troubling given its disease potential, and establishes another route
      for the introduction of this economically damaging subspecies into the US or
      elsewhere, a threat potentially compounded by the presence of a previously
      unknown form of X. fastidiosa. 

PMID- 25379726
TI  - Development of a mimotope vaccine targeting the Staphylococcus aureus quorum
      sensing pathway.
AB  - A major hurdle in vaccine development is the difficulty in identifying relevant
      target epitopes and then presenting them to the immune system in a context that
      mimics their native conformation. We have engineered novel virus-like-particle
      (VLP) technology that is able to display complex libraries of random peptide
      sequences on a surface-exposed loop in the coat protein without disruption of
      protein folding or VLP assembly. This technology allows us to use the same VLP
      particle for both affinity selection and immunization, integrating the power of
      epitope discovery and epitope mimicry of traditional phage display with the high
      immunogenicity of VLPs. Previously, we showed that using affinity selection with
      our VLP platform identifies linear epitopes of monoclonal antibodies and
      subsequent immunization generates the proper antibody response. To test if our
      technology could identify immunologic mimotopes, we used affinity selection on a
      monoclonal antibody (AP4-24H11) that recognizes the Staphylococcus aureus
      autoinducing peptide 4 (AIP4). AIP4 is a secreted eight amino acid, cyclized
      peptide produced from the S. aureus accessory gene regulator (agrIV) quorum
      sensing operon. The agr system coordinates density dependent changes in gene
      expression, leading to the upregulation of a host of virulence factors, and
      passive transfer of AP4-24H11 protects against S. aureus agrIV-dependent
      pathogenicity. In this report, we identified a set of peptides displayed on VLPs
      that bound with high specificity to AP4-24H11. Importantly, similar to passive
      transfer with AP4-24H11, immunization with a subset of these VLPs protected
      against pathogenicity in a mouse model of S. aureus dermonecrosis. These data are
      proof of principle that by performing affinity selection on neutralizing
      antibodies, our VLP technology can identify peptide mimics of non-linear epitopes
      and that these mimotope based VLP vaccines provide protection against pathogens
      in relevant animal models. 

PMID- 25379727
TI  - Engagement with health agencies on twitter.
AB  - OBJECTIVE: To investigate factors associated with engagement of U.S. Federal
      Health Agencies via Twitter. Our specific goals are to study factors related to
      a) numbers of retweets, b) time between the agency tweet and first retweet and c)
      time between the agency tweet and last retweet. METHODS: We collect 164,104
      tweets from 25 Federal Health Agencies and their 130 accounts. We use negative
      binomial hurdle regression models and Cox proportional hazards models to explore
      the influence of 26 factors on agency engagement. Account features include
      network centrality, tweet count, numbers of friends, followers, and favorites.
      Tweet features include age, the use of hashtags, user-mentions, URLs, sentiment
      measured using Sentistrength, and tweet content represented by fifteen semantic
      groups. RESULTS: A third of the tweets (53,556) had zero retweets. Less than 1%
      (613) had more than 100 retweets (mean  = 284). The hurdle analysis shows that
      hashtags, URLs and user-mentions are positively associated with retweets;
      sentiment has no association with retweets; and tweet count has a negative
      association with retweets. Almost all semantic groups, except for geographic
      areas, occupations and organizations, are positively associated with retweeting.
      The survival analyses indicate that engagement is positively associated with
      tweet age and the follower count. CONCLUSIONS: Some of the factors associated
      with higher levels of Twitter engagement cannot be changed by the agencies, but
      others can be modified (e.g., use of hashtags, URLs). Our findings provide the
      background for future controlled experiments to increase public health engagement
      via Twitter.

PMID- 25379728
TI  - Conservation weighting functions enable covariance analyses to detect
      functionally important amino acids.
AB  - The explosive growth in the number of protein sequences gives rise to the
      possibility of using the natural variation in sequences of homologous proteins to
      find residues that control different protein phenotypes. Because in many cases
      different phenotypes are each controlled by a group of residues, the mutations
      that separate one version of a phenotype from another will be correlated. Here we
      incorporate biological knowledge about protein phenotypes and their variability
      in the sequence alignment of interest into algorithms that detect correlated
      mutations, improving their ability to detect the residues that control those
      phenotypes. We demonstrate the power of this approach using simulations and
      recent experimental data. Applying these principles to the protein families
      encoded by Dscam and Protocadherin allows us to make testable predictions about
      the residues that dictate the specificity of molecular interactions. 

PMID- 25379729
TI  - Respiratory gating during stereotactic body radiotherapy for lung cancer reduces
      tumor position variability.
AB  - PURPOSE: We evaluated the effects of respiratory gating on treatment accuracy in
      lung cancer patients undergoing lung stereotactic body radiotherapy by using
      electronic portal imaging device (EPID) images. MATERIALS AND METHODS: Our study
      population consisted of 30 lung cancer patients treated with stereotactic body
      radiotherapy (48 Gy/4 fractions/4 to 9 days). Of these, 14 were treated with-
      (group A) and 16 without gating (group B); typically the patients whose tumors
      showed three-dimensional respiratory motion ?5 mm were selected for gating. Tumor
      respiratory motion was estimated using four-dimensional computed tomography
      images acquired during treatment simulation. Tumor position variability during
      all treatment sessions was assessed by measuring the standard deviation (SD) and
      range of tumor displacement on EPID images. The two groups were compared for
      tumor respiratory motion and position variability using the Mann-Whitney U test.
      RESULTS: The median three-dimensional tumor motion during simulation was greater
      in group A than group B (9 mm, range 3-30 mm vs. 2 mm, range 0-4 mm; p<0.001). In
      groups A and B the median SD of the tumor position was 1.1 mm and 0.9 mm in the
      craniocaudal- (p = 0.24) and 0.7 mm and 0.6 mm in the mediolateral direction (p =
      0.89), respectively. The median range of the tumor position was 4.0 mm and 3.0 mm
      in the craniocaudal- (p = 0.21) and 2.0 mm and 1.5 mm in the mediolateral
      direction (p = 0.20), respectively. CONCLUSIONS: Although patients treated with
      respiratory gating exhibited greater respiratory tumor motion during treatment
      simulation, tumor position variability in the EPID images was low and comparable
      to patients treated without gating. This demonstrates the benefit of respiratory
      gating.

PMID- 25379730
TI  - LAT software induced savings on medical costs of alcohol addicts' care--results
      from a matched-pairs case-control study.
AB  - Lesch Alcoholism Typology (LAT) is one of the most widely used clinical
      typologies of alcohol addiction. Study tested whether introduction of LAT
      software in clinical practice leaded to improved outcomes and reduced costs.
      Retrospective matched-pairs case-control cost comparison study was conducted at
      the Regional Addiction Center of the University Clinic in Serbia involving 250
      patients during the four-year period. Mean relapse frequency followed by
      outpatient detoxification was 0.42 +/- 0.90 vs. 0.70 +/- 1.66 (LAT/non-LAT; p =
      0.267). Adding relapses after inpatient treatment total mean-number of relapses
      per patient was 0.70 +/- 1.74 vs. 0.97 +/- 1.89 (LAT/non-LAT; p = 0.201).
      However, these relapse frequency differentials were not statistically
      significant. Total hospital costs of Psychiatry clinic based non-LAT addicts'
      care (? 54,660) were significantly reduced to ? 36,569 after initiation of LAT.
      Mean total cost per patient was reduced almost by half after initiation of LAT
      based treatment: ? 331 +/- 381 vs. ? 626 +/- 795 (LAT/non-LAT; p = 0.001). Mean
      cost of single psychiatry clinic admission among non-LAT treatment group was ?
      320 +/- 330 (CI 95% 262-378) and among LAT ? 197 +/- 165 (CI 95% 168-226) (p =
      0.019). Mean LAT software induced net savings on psychiatric care costs were ?
      144 per patient. Total net savings on hospital care including F10 associated
      somatic co-morbidities amounted to ? 295 per patient. More sensitive diagnostic
      assessment and sub-type specific pharmacotherapy and psychotherapy following
      implementation of LAT software lead to significant savings on costs of hospital
      care.

PMID- 25379731
TI  - Anatomic distribution of nerves and microvascular density in the human anterior
      vaginal wall: prospective study.
AB  - BACKGROUND: The presence of the G-spot (an assumed erotic sensitive area in the
      anterior wall of the vagina) remains controversial. We explored the
      histomorphological basis of the G-spot. METHODS: Biopsies were drawn from a 12
      o'clock direction in the distal- and proximal-third areas of the anterior vagina
      of 32 Chinese subjects. The total number of protein gene product 9.5
      immunoreactive nerves and smooth muscle actin-immunoreactive blood vessels in
      each specimen was quantified using the avidin-biotin-peroxidase assay. RESULTS:
      Vaginal innervation was observed in the lamina propria and muscle layer of the
      anterior vaginal wall. The distal-third of the anterior vaginal wall had
      significantly richer small-nerve-fiber innervation in the lamina propria than the
      proximal-third (p = 0.000) and in the vaginal muscle layer (p = 0.006). There
      were abundant microvessels in the lamina propria and muscle layer, but no small
      vessels in the lamina propria and few in the muscle layer. Significant
      differences were noted in the number of microvessels when comparing the distal-
      with proximal-third parts in the lamina propria (p = 0.046) and muscle layer (p =
      0.002). CONCLUSIONS: Significantly increased density of nerves and microvessels
      in the distal-third of the anterior vaginal wall could be the histomorphological
      basis of the G-spot. Distal anterior vaginal repair could disrupt the normal
      anatomy, neurovascular supply and function of the G-spot, and cause sexual
      dysfunction.

PMID- 25379733
TI  - Short-term complications associated with TPLO in dogs using 2.0 and 2.7 mm
      plates.
AB  - The purpose of this study was to evaluate short-term complications associated
      with the tibial plateau leveling osteotomy (TPLO) procedure in dogs of small and
      medium sizes. These study findings could then be compared with similar studies in
      dogs of all sizes. Ninety-eight procedures (82 dogs) using 2 or 2.7 mm TPLO
      plates were included spanning a 6 yr period with a minimum of an 8 wk follow-up
      period. The overall complication rate was 36%. Complications were grouped into
      three categories: intraoperative (2%), those occurring up to 2 wk postoperatively
      (11%), and those occurring >2 wk postoperatively (30%). Radiographic evidence of
      delayed healing of the TPLO osteotomy site was the most common complication in
      the dogs (9%), none of which had clinical signs attributed to delayed healing.
      Other common complications included patellar tendon thickening (8%) and tibial
      tuberosity fracture (6%). Seven percent of the complications were considered
      major (requiring additional surgical intervention). Fifty-two percent of
      complications did not require treatment. Short-term complications should not
      dissuade an experienced surgeon from performing the TPLO procedure in small- and
      medium-sized dogs.

PMID- 25379732
TI  - A rare duplication on chromosome 16p11.2 is identified in patients with psychosis
      in Alzheimer's disease.
AB  - Epidemiological and genetic studies suggest that schizophrenia and autism may
      share genetic links. Besides common single nucleotide polymorphisms, recent data
      suggest that some rare copy number variants (CNVs) are risk factors for both
      disorders. Because we have previously found that schizophrenia and psychosis in
      Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs
      reported in schizophrenia and autism are also linked to AD+P. We searched for
      CNVs associated with AD+P in 7 recurrent CNV regions that have been previously
      identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad
      BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was
      identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without
      psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855
      non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was
      similar to that reported previously in schizophrenia (0.46%). This duplication
      CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The
      16p11.2 duplication has been associated with developmental delay, intellectual
      disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar
      disorder. These two AD+P patients had no personal of, nor any identified family
      history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our
      case report is the first suggestion that 16p11.2 duplication is also linked to
      AD+P. Although rare, this CNV may have an important role in the development of
      psychosis. 

PMID- 25379734
TI  - Adverse interaction between colchicine and ketoconazole in a Chinese shar pei.
AB  - A Chinese shar pei with a 2 yr history of episodic fever, lethargy, and shifting
      lameness was presumptively diagnosed with familial shar pei fever but had never
      been treated for the syndrome. After being presented for a superficial pyoderma
      with possible dermatophyte coinfection, treatment with a cephalosporin and
      ketoconazole were prescribed. One wk later, colchicine was initiated for familial
      shar pei fever using cautious dose escalation. Nevertheless, gastrointestinal
      toxicity, skeletal muscle myopathy, and hepatotoxicity developed within 2 wk.
      Abrupt resolution of gastrointestinal toxicity and myopathy followed drug
      withdrawal. However, escalating liver enzyme activity and hyperbilirubinemia led
      to liver biopsy to rule out an antecedent hepatopathy. Biopsy characterized
      canalicular cholestasis and colchicine-associated metaphase arrest and ring
      mitoses reflecting repression of mitotic spindle formation. Signs of illness
      completely resolved 3 mo after drug discontinuation. Although avoidable adverse
      interactions between ketoconazole and drugs reliant on cytochrome oxidase
      biotransformation and/or drug efflux mediated by multiple drug-resistant
      transporters are well documented in humans, these are rarely reported in
      veterinary patients. This case exemplifies an important and avoidable
      ketoconazole/colchicine drug interaction from which the patient completely
      recovered. The dog tested negative for the canine MDR1 loss of function mutation
      that also might potentiate colchicine toxicity. 

PMID- 25379735
TI  - Assessment of Digoxin-Specific Fab Fragment Dosages in Digoxin Poisoning.
AB  - Digoxin poisoning still remains a common cause of morbidity and mortality.
      Fortunately, digoxin-specific Fab fragments are commercially available as an
      antidote. However, these Fab fragments are several thousand dollars per vial.
      There is a standardized formula to calculate appropriate Fab fragment dosage
      based on the serum digoxin concentration. This can greatly reduce the amount of
      Fab fragment administered. There is also an empiric dosing guideline recommending
      6-10 vials be given; however, this may result in higher amounts of Fab fragments
      being administered than required. We performed this study to assess the amounts
      of digoxin-specific Fab fragments administered in the treatment of digoxin
      poisonings recorded in a poison control system database from January 1, 2000, to
      December 31, 2009, in which digoxin serum concentrations were available. This was
      a retrospective study of 278 patients, 107 with acute poisonings (group A) and
      171 following chronic poisoning (group B). In group A, the calculated Fab dose
      was higher than the calculated dose based on available concentrations in 39 (36%)
      of group A and 15 (9%) of group B patients. The average wholesale price cost of
      the excessive dosages ranged from $4818 to as high as $50,589 per patient. Our
      data suggests that clinician education on digoxin poisoning and the use of the
      standardized formula to calculate the Fab dose may decrease over utilization and
      decrease costs associated with the administration of digoxin-specific Fab
      fragments in the treatment of digoxin poisonings. 

PMID- 25379736
TI  - Comparison of Arginine Hydrochloride and Acetazolamide for the Correction of
      Metabolic Alkalosis in Pediatric Patients.
AB  - Metabolic alkalosis is a common acid-base disturbance occurring in critically ill
      pediatric patients. Acetazolamide and arginine hydrochloride are pharmacologic
      agents used at our institution for patients refractory to first-line therapy or
      those unable to tolerate fluid replacement. The objective of this retrospective
      review was to determine if a course of arginine hydrochloride or acetazolamide
      was more effective at correcting metabolic alkalosis within a 24-hour period.
      Patients included received a course of acetazolamide or arginine hydrochloride
      for metabolic alkalosis with a repeat metabolic panel 18-30 hours after treatment
      initiation. Exclusion criteria consisted of previous treatment with either drug
      within 24 hours or a documented metabolic disorder. Efficacy was determined by
      proportion of patients achieving resolution of metabolic alkalosis (treatment
      success: serum CO2 <30 mmol/L and Cl >96 mmol/L). Additionally, mean change in
      serum bicarbonate and chloride concentrations was assessed. Thirty-four patients
      met inclusion criteria, 19 patients received acetazolamide and 15 patients
      received arginine hydrochloride. Treatment success was similar in patients
      receiving acetazolamide and arginine hydrochloride (37% vs. 7%, P = 0.053).
      Correction of serum bicarbonate was observed in more patients treated with
      acetazolamide (42% vs. 7%, P = 0.047). Both groups had a similar increase in mean
      serum chloride concentration (5.7 +/- 5.3 vs. 4.4 +/- 4.4 mmol/L, P = 0.458).
      Mean decrease in serum bicarbonate concentration was equivalent between groups
      (5.6 +/- 5.2 vs. 2.8 +/- 4.7, mmol/L, P = 0.110). Acetazolamide and arginine
      hydrochloride appear to be equally effective in correcting metabolic alkalosis in
      critically ill pediatric patients.

PMID- 25379737
TI  - Diffuse Autoimmune Enteropathy and Colopathy in an Adult Patient Successfully
      Treated With Adalimumab and a Review of the Literature.
AB  - Autoimmune enteropathy (AIE) is a rare disease that causes intractable diarrhea
      not responsive to a gluten free diet and must be distinguished from refractory
      sprue. It is associated with circulating autoantibodies against goblet cells and
      enterocytes. AIE mainly involves the small intestines, with very few cases
      reported in adults. Because of the paucity of cases, the epidemiology of the
      disease remains unclear, and treatment is based on the cases found in the
      literature. Of the 35 adult cases reported, only 4 involved the colon. Because of
      the low number of cases, there have been no clear recommendations on treatment
      modalities with most reports heavily emphasizing steroids as the mainstay of
      treatment. We present the case of adult female patient who developed postpartum
      AIE and colopathy with profuse diarrhea successfully treated with adalimumab and
      a review of the literature. To the best of our knowledge, this case is only the
      fourth case of a tumor necrosis factor alpha antagonist being used in the
      treatment of AIE and the first case of adalimumab being used. 

PMID- 25379738
TI  - Stray light correction on array spectroradiometers for optical radiation risk
      assessment in the workplace.
AB  - The European directive 2006/25/EC requires the employer to assess and, if
      necessary, measure the levels of exposure to optical radiation in the workplace.
      Array spectroradiometers can measure optical radiation from various types of
      sources; however poor stray light rejection affects their accuracy. A stray light
      correction matrix, using a tunable laser, was developed at the National Institute
      of Standards and Technology (NIST). As tunable lasers are very expensive, the
      purpose of this study was to implement this method using only nine low power
      lasers; other elements of the correction matrix being completed by interpolation
      and extrapolation. The correction efficiency was evaluated by comparing CCD
      spectroradiometers with and without correction and a scanning double
      monochromator device as reference. Similar to findings recorded by NIST, these
      experiments show that it is possible to reduce the spectral stray light by one or
      two orders of magnitude. In terms of workplace risk assessment, this spectral
      stray light correction method helps determine exposure levels, with an acceptable
      degree of uncertainty, for the majority of workplace situations. The level of
      uncertainty depends upon the model of spectroradiometers used; the best results
      are obtained with CCD detectors having an enhanced spectral sensitivity in the UV
      range. Thus corrected spectroradiometers require a validation against a scanning
      double monochromator spectroradiometer before using them for risk assessment in
      the workplace. 

PMID- 25379741
TI  - The soil biota composition along a progressive succession of secondary vegetation
      in a karst area.
AB  - Karst ecosystems are fragile and are in many regions degraded by anthropogenic
      activities. Current management of degraded karst areas focuses on aboveground
      vegetation succession or recovery and aims at establishing a forest ecosystem.
      Whether progressive succession of vegetation in karst areas is accompanied by
      establishment of soil biota is poorly understood. In the present study, soil
      microbial and nematode communities, as well as soil physico-chemical properties
      were studied along a progressive succession of secondary vegetation (from
      grassland to shrubland to forest) in a karst area in southwest China. Microbial
      biomass, nematode density, ratio of fungal to bacterial biomass, nematode
      structure index, and nematode enrichment index decreased with the secondary
      succession in the plant community. Overall, the results indicated a pattern of
      declines in soil biota abundance and food web complexity that was associated with
      a decrease in soil pH and a decrease in soil organic carbon content with the
      progressive secondary succession of the plant community. Our findings suggest
      that soil biota amendment is necessary during karst ecosystem restoration and
      establishment and management of grasslands may be feasible in karst areas. 

PMID- 25379742
TI  - Vengeance is self-focused: Comparing vengeful to anger-driven responses.
AB  - Prior definitions and empirical research do not distinguish responses to
      transgressions driven by feelings of revenge from responses to transgressions
      driven by feelings of anger. We used autobiographical recalls to examine
      differences between vengeful and anger-driven responses. Our findings revealed
      that vengeful responses are not the same as anger-driven responses. Compared to
      anger-driven responses, vengeful responses resulted more from offences that
      induce a self-threat, which elicited more intense negative self-conscious
      emotions and more rumination. Moreover, compared to anger-driven responses,
      vengeful responses consisted more of behaviours that induced a self-threat to the
      other person, were motivated more by intrapersonal goals, were more delayed,
      elicited more positive emotions and resulted in less relationship restoration.
      Together, these findings suggest that more so than anger-driven responses,
      vengeance is self-focused. 

PMID- 25379743
TI  - Canthin-6-one displays antiproliferative activity and causes accumulation of
      cancer cells in the G2/M phase.
AB  - Canthinones are natural substances with a wide range of biological activities,
      including antipyretic, antiparasitic, and antimicrobial. Antiproliferative and/or
      cytotoxic effects of canthinones on cancer cells have also been described,
      although their mechanism of action remains ill defined. To gain better insight
      into this mechanism, the antiproliferative effect of a commercially available
      canthin-6-one (1) was examined dose-dependently on six cancer cell lines (human
      prostate, PC-3; human colon, HT-29; human lymphocyte, Jurkat; human cervix, HeLa;
      rat glioma, C6; and mouse embryonic fibroblasts, NIH-3T3). Cytotoxic effects of 1
      were investigated on the same cancer cell lines by procaspase-3 cleavage and on
      normal human skin fibroblasts. Strong antiproliferative effects of the compound
      were observed in all cell lines, whereas cytotoxic effects were very dependent on
      cell type. A better definition of the mechanism of action of 1 was obtained on PC
      3 cells, by showing that it decreases BrdU incorporation into DNA by 60% to 80%
      and mitotic spindle formation by 70% and that it causes a 2-fold accumulation of
      cells in the G2/M phase of the cell cycle. Together, the data suggest that the
      primary effect of canthin-6-one (1) is antiproliferative, possibly by interfering
      with the G2/M transition. Proapoptotic effects might result from this disturbance
      of the cell cycle. 

PMID- 25379744
TI  - Crisis in medicine: have we traded technology for our six senses?

PMID- 25379745
TI  - Visualization and reduction of a mensical capsular junction tear in the knee: an
      arthroscopic surgical technique.
AB  - Meniscal injuries commonly occur concomitantly with anterior cruciate ligament
      (ACL) injuries. Although many types of meniscal injuries have been described in
      the literature, there has not been much focus on meniscal capsular junction (MCJ)
      tears. This lack of attention is concerning given that, in a survey of 67
      orthopedic surgeons, 88% indicated that MCJ tears could be a source of chronic
      pain. In addition, we reviewed 781 ACL reconstructions at our clinic and found a
      12.3% incidence of MCJ tear with primary ACL injury and a 23.6% incidence of MCJ
      tear with revision ACL reconstruction. In this article, we describe an
      arthroscopic repair technique for MCJ tears at the posterior aspect of the medial
      meniscus root. The repair uses an accessory posterior medial portal. The
      technique can also be used for significant posterior medial capsular tears.

PMID- 25379746
TI  - Lower extremity injuries in snowboarders.
AB  - The popularity of skiing and snowboarding has increased tremendously over the
      past few decades. Whereas skiing has been an established winter sport for some
      time, snowboarding was created only in the 1960s. The great surge in popularity
      of snowboarding was sparked by its inclusion in the 1998 Winter Olympics. With
      increased participation in these winter activities has come a tremendous rise in
      injuries, despite equipment changes and promotion of safety behavior. Although
      participants in these sports share many common lower extremity injuries, the
      unique characteristics of skiing and snowboarding lead to marked differences in
      injury rates and mechanisms of many specific injuries of knee, foot, and ankle.
      In this article, we review the literature on the epidemiology of lower extremity
      injuries associated with snowboarding and the associated mechanisms of injury.

PMID- 25379747
TI  - Large-diameter femoral heads in total hip arthroplasty: an evidence-based review.
AB  - Recent advances in the wear characteristics and material properties of highly
      cross-linked polyethyl-ene and fourth-generation ceramic bearings have led to
      increasing use of large-diameter (>= 36 mm) femoral heads in total hip
      arthroplasty (THA). In this article, we review the current concepts and
      principles behind use of large-diameter ceramic or cobalt-chromium femoral heads
      on polyethylene bearings in THA. We specifically review the biomechanics, some of
      the early concerns about polyethylene wear and rim fractures, recent improvements
      in material properties of polyethylene and ceramic bearings, dislocation rates,
      and clinical and functional outcomes of large-diameter heads in THA. Recent
      literature suggests that the incidence of dislocation has been substantially
      reduced because of improvements in jump distance and impingement-free range of
      motion with use of large-diameter heads. Limited evidence suggests excellent
      short-term and midterm clinical and functional outcomes with these heads. 

PMID- 25379748
TI  - The role of computed tomography for postoperative evaluation of percutaneous
      sacroiliac screw fixation and description of a "safe zone".
AB  - We sought to determine whether computed tomography (CT) is an accurate tool for
      evaluation of reduction, prediction of neurologic deficit, and evaluation of need
      for revision surgery in unstable pelvic ring injuries treated with percutaneous
      sacroiliac (SI) screw fixation and whether any neural foramen penetration
      violation is safe. Using medical records and radiographic data, we
      retrospectively evaluated 46 patients with 51 fractures or widenings of the SI
      joint that were surgically treated with percutaneous SI screw fixation, either
      alone or associated with anterior fixation. Using the Young and Burgess
      classification, there were 3 vertical shear injuries, 13 lateral compression
      injuries, 17 anterior-posterior injuries, 7 sacral fractures, and 6 combination
      or unclassifiable pelvic injuries. Satisfactory reduction was obtained in all
      cases. All patients had postoperative CT scans, and 23 of 51 screws had some
      foramen penetration with an average of 3.3 mm (range, 1.4-7.0 mm). After
      percutaneous screw fixation, 10 of 46 patients had postoperative neurologic
      deficit, 4 of which were unchanged from preoperative evaluation. Of the 6
      patients with new or worsened neurologic deficit, CT showed neural foramen
      penetration of 2.1 and 7.0 mm in 2 patients. Both patients underwent screw
      revision, resulting in improved neurologic deficit. The remaining 4 patients did
      not have foramen penetration; their neurologic function improved, with full
      return at 6 weeks without screw removal. Neural foramen penetration documented
      with CT did not correlate with neurologic deficit unless the penetration was
      greater than 2.7 mm. Postoperative CT showing neural foramen penetration was the
      cause of revision surgery in 2 of 10 patients with postoperative neurologic
      deficit after percutaneous SI screw fixation. Based on these findings, we
      recommend postoperative CT only in those cases where there is new neurologic
      deficit and screw removal if foramen penetration is greater than 2.1 mm. We also
      describe a new "safe zone" for screw insertion encompassing the superior 2 mm of
      the sacral foramen with adequate pelvic reduction. 

PMID- 25379749
TI  - Dynamic magnetic resonance imaging of partial-thickness retearing of distal
      biceps tendon after endobutton repair.
AB  - We report a case of ruptured distal biceps tendon repaired with a 1-incision
      Endobutton technique with longitudinal clinical and dynamic magnetic resonance
      imaging (MRI) follow-up. During the postoperative period, heterotopic
      ossification (HO) adjacent to the radial tuberosity and retearing of the repaired
      distal biceps tendon were visible on imaging studies. This prompted gentler
      rehabilitation. By 1-year follow-up, the patient had returned to preinjury
      activity levels without additional surgery. In this case, dynamic MRI revealed
      the space-occupying nature of the focus of HO with resultant narrowing of the
      radioulnar space. This may have contributed to tendon impingement, retearing, and
      remodeling. Potential implications for gentler postoperative rehabilitation in
      patients with this pattern of HO are discussed.

PMID- 25379750
TI  - Application of epoxy resin to a solid-foam pelvic model: creating a dry-erase
      pelvis.
AB  - The value of preoperative planning and templating has been well-established in
      fracture surgery. We have found that using 3-dimensional (3-D) models in
      preoperative planning aids in the understanding of anatomy, fracture-reduction
      techniques, and fixation methods, particularly in pelvic and acetabular
      fractures. To facilitate the correction of errors and reuse for future cases, we
      coat pelvic models with dry-erase epoxy resin. Fracture lines and planned
      implants are drawn onto the models with dry-erase markers. The creation of 3-D
      planning tools is useful in understanding the anatomy of pelvic and acetabular
      fractures.

PMID- 25379751
TI  - To outsource or not to outsource your physical therapy service line management?

PMID- 25379752
TI  - Pilot study for an orthopedic surgical training laboratory for basic motor
      skills.
AB  - The most effective way to teach and assess a resident's knowledge of
      musculoskeletal medicine, including orthopedic-specific surgical skills, remains
      unclear. We designed a surgical skills training session to educate junior-level
      orthopedic residents in 4 core areas: comfort with basic power equipment,
      casting/splinting, suturing, and surgical instrument identification. As part of
      the study reported here, 11 orthopedic residents (postgraduate year 1-3)
      completed a skills session and were evaluated with written examinations and an
      ankle fracture model before and after the session. Four other junior residents
      were unable to attend the session because of clinical responsibilities. For the
      group of 11 residents who completed the written examination, mean (SD) presession
      percentile was 87.3 (10.4), mean (SD) postsession percentile was 92 (8.4), median
      was 96, and mode was 96. There was a significant pre-post difference among all
      test takers, regardless of training level (P < .05). In the ankle fracture model,
      for the entire group, mean (SD) overall presession percentile was 68.6 (13.9),
      and mean (SD) overall postsession percentile was 95.2 (5.2). There was a
      significant pre-post difference among all test takers, regardless of training
      level (P = .03). An intensive laboratory has the potential to improve junior
      level residents' basic surgical skills and knowledge.

PMID- 25379753
TI  - Does a prior hip arthroscopy affect clinical outcomes in metal-on-metal hip
      resurfacing arthroplasty?
AB  - The effect of a prior hip arthroscopy on the outcome of a subsequent metal-on
      metal hip resurfacing arthroplasty (HRA) has not been studied. Forty-three
      patients received an HRA after a prior hip arthroscopy (arthroscopy cohort). A
      1:2 matching analysis was performed to formulate a control cohort of 86 patients.
      Range of motion, Harris Hip Score, University of California at Los Angeles
      activity score, Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) score, and Short Form-12 scores were assessed at 6 weeks, 3 months, 6
      months, 1 year, and most recent follow-up visits. At 6-week follow-up, the
      arthroscopy cohort showed a decreased WOMAC score compared with the control
      cohort (72.9 [SD, 15.5] vs 80.5 [SD, 11.8], respectively; P = .05). However, no
      significant difference was appreciated between the 2 cohorts for any of the
      clinical indices measured after 6 weeks postoperatively. This study shows that a
      prior hip arthroscopy does not appear to affect the short-term, clinical outcomes
      of a metal-on-metal HRA.

PMID- 25379754
TI  - Improving visual estimates of cervical spine range of motion.
AB  - Cervical spine range of motion (ROM) is a common measure of cervical conditions,
      surgical outcomes, and functional impairment. Although ROM is routinely assessed
      by visual estimation in clinical practice, visual estimates have been shown to be
      unreliable and inaccurate. Reliable goniometers can be used for assessments, but
      the associated costs and logistics generally limit their clinical acceptance. To
      investigate whether training can improve visual estimates of cervical spine ROM,
      we asked attending surgeons, residents, and medical students at our institution
      to visually estimate the cervical spine ROM of healthy subjects before and after
      a training session. This training session included review of normal cervical
      spine ROM in 3 planes and demonstration of partial and full motion in 3 planes by
      multiple subjects. Estimates before, immediately after, and 1 month after this
      training session were compared to assess reliability and accuracy. Immediately
      after training, errors decreased by 11.9 degrees  (flexion-extension), 3.8
      degrees  (lateral bending), and 2.9 degrees  (axial rotation). These improvements
      were statistically significant. One month after training, visual estimates
      remained improved, by 9.5 degrees , 1.6 degrees , and 3.1 degrees , respectively,
      but were statistically significant only in flexion-extension. Although the
      accuracy of visual estimates can be improved, clinicians should be aware of the
      limitations of visual estimates of cervical spine ROM. Our study results support
      scrutiny of visual assessment of ROM as a criterion for diagnosing permanent
      impairment or disability.

PMID- 25379755
TI  - Surgery for blastomycosis of the spine.
AB  - Blastomycosis is a rare fungal infection that primarily produces acute lung
      infections but may disseminate to multiple sites, including the spine. Once
      vertebral involvement occurs, an untreated infection may result in vertebral body
      destruction and paraspinal and epidural abscess formation followed by neurologic
      injury and loss of structural integrity of the spine. We report the case of a 30
      year-old man who had pulmonary blastomycosis (treated with oral itraconazole for
      6 months) and presented with a 2-month history of mild thoracolumbar back pain
      and numbness and tingling in the lower extremities, but no neurologic deficits.
      Imaging revealed a destructive lesion of T11 with an extensive paravertebral and
      retropleural abscess tracking a spinal level above and below with extension into
      the spinal canal. The patient underwent incision and drainage, culture
      procurement and corpectomy of T11 with autogenous rib graft in a titanium cage,
      and, 1 week later, posterior fusion and instrumentation. Cultures were positive
      for Blastomycosis dermatitidis. Oral itraconazole was continued. Blastomycosis
      that disseminates to the spine may cause serious neurologic and structural
      complications. In most cases, long-term use of antifungal medication eradicates
      the infection. Should medical treatment fail, however, surgery is a useful
      option.

PMID- 25379756
TI  - Sacral insufficiency fracture after partial sacrectomy.
AB  - A 66-year-old woman presented with severe lower back pain. Magnetic resonance
      imaging (MRI) revealed a large, soft-tissue mass-a chordoma-at the S3-S4 level,
      eroding most of the S3 vertebral body and extending into S4. The mass extended
      beyond the involved sacrococcygeal segments and dorsally beyond normal cortical
      margins of the sacrum and coccyx. The patient underwent a noninstrumented
      sacrectomy distal to the S2 foramen, lumbar laminectomy L5, S1 and S2, and thecal
      sac transaction at the S3 nerve roots. At the third postoperative month, she
      noted onset of extreme pain in her groin and left thigh. MRI showed increased
      signal on short tau inversion recovery sequences, and T2-weighted images revealed
      a left sacral ala stress fracture with a vertically oriented fracture line. Over
      the next 3 months, the patient had a resolution of her pain and, at 2-year follow
      up, the patient remained disease-free. Surgeons contemplating performing partial
      sacrectomies should bear in mind, even with preservation of the S1 body, that the
      potential for fracture exists as evidenced by our patient. It is our opinion that
      this patient did not require instrumentation but a more gradual rehabilitation
      program.

PMID- 25379757
TI  - Concurrent treatment of a middle-third clavicle fracture and type IV
      acromioclavicular dislocation.
AB  - Acromioclavicular (AC) dislocation with an associated displaced fracture of the
      middle third of the clavicle is a rare injury with no established standard
      treatment. Previous AC fixation techniques described have not included
      simultaneous internal fixation of the clavicle. We present the case of a 19-year
      old man who sustained this combined injury pattern with a type IV AC dislocation.
      He underwent open reduction and internal fixation of the clavicle fracture with
      open reduction of the AC joint and coracoclavicular (CC) screw fixation through
      the plate to stabilize the AC dislocation. The CC screw was removed 3 months
      after surgery. By 1-year follow-up, the patient had returned to manual labor and
      normal activities of daily living. In comparison with previously described
      treatment, his case highlights a unique approach to this rare shoulder entity.

PMID- 25379758
TI  - Neonatal physeal separation of distal humerus during cesarean section.
AB  - Diagnosing physeal separation of the distal humerus in a newborn can be
      challenging. Skeletal immaturity and absence of secondary ossification centers
      make radiographic diagnosis difficult for inexperienced providers. This fracture
      is seen in the setting of complicated deliveries with excessive traction and
      rotation applied to the forearm. We report a case of physeal separation of the
      distal humerus in a newborn as a complication of cesarean section and describe
      the intervention used and the short-term results.

PMID- 25379759
TI  - Novel approach to characterizing the growth of a fouling layer during membrane
      filtration via optical coherence tomography.
AB  - Fouling control is one of the critical issues in membrane filtration and plays a
      very important role in water/wastewater treatment. Better understanding of the
      underlying fouling mechanisms entails novel characterization techniques that can
      realize a real-time noninvasive observation and provide high resolution images
      recording the formation of a fouling layer. This work presents a characterization
      method based on optical coherence tomography (OCT), which is able to detect the
      internal structures and motions by analyzing the interference signals. An OCT
      system was incorporated with a laboratory-scale membrane filtration system, and
      the growth of the fouling layer was observed by using the structural imaging.
      Taking advantage of the Doppler effects, the OCT-based characterization also
      provided the velocity profiles of the fluid field, which are of great value in
      analyzing the formation of the cake layer. The characterization results clearly
      reveal for the first time the evolution of the morphology of the cake layer under
      different microhydrodynamic environments. This study demonstrates that OCT-based
      characterization is a powerful tool for investigating the dynamic processes
      during membrane fouling. 

PMID- 25379760
TI  - Regulation of coagulation factor XI expression by microRNAs in the human liver.
AB  - High levels of factor XI (FXI) increase the risk of thromboembolic disease.
      However, the genetic and environmental factors regulating FXI expression are
      still largely unknown. The aim of our study was to evaluate the regulation of FXI
      by microRNAs (miRNAs) in the human liver. In silico prediction yielded four miRNA
      candidates that might regulate FXI expression. HepG2 cells were transfected with
      miR-181a-5p, miR-23a-3p, miR-16-5p and miR-195-5p. We used mir-494, which was not
      predicted to bind to F11, as a negative control. Only miR-181a-5p caused a
      significant decrease both in FXI protein and F11 mRNA levels. In addition,
      transfection with a miR-181a-5p inhibitor in PLC/PRF/5 hepatic cells increased
      both the levels of F11 mRNA and extracellular FXI. Luciferase assays in human
      colon cancer cells deficient for Dicer (HCT-DK) demonstrated a direct interaction
      between miR-181a-5p and 3'untranslated region of F11. Additionally, F11 mRNA
      levels were inversely and significantly correlated with miR-181a-5p levels in 114
      healthy livers, but not with miR-494. This study demonstrates that FXI expression
      is directly regulated by a specific miRNA, miR-181a-5p, in the human liver.
      Future studies are necessary to further investigate the potential consequences of
      miRNA dysregulation in pathologies involving FXI. 

PMID- 25379762
TI  - ["Everyone is in" - cover picture contest starts in its second round].

PMID- 25379763
TI  - [Prolongation of psychiatric training - pro].

PMID- 25379761
TI  - Reduction of T cell receptor diversity in NOD mice prevents development of type 1
      diabetes but not Sjogren's syndrome.
AB  - Non-obese diabetic (NOD) mice are well-established models of independently
      developing spontaneous autoimmune diseases, Sjogren's syndrome (SS) and type 1
      diabetes (T1D). The key determining factor for T1D is the strong association with
      particular MHCII molecule and recognition by diabetogenic T cell receptor (TCR)
      of an insulin peptide presented in the context of I-Ag7 molecule. For SS the
      association with MHCII polymorphism is weaker and TCR diversity involved in the
      onset of the autoimmune phase of SS remains poorly understood. To compare the
      impact of TCR diversity reduction on the development of both diseases we
      generated two lines of TCR transgenic NOD mice. One line expresses transgenic
      TCRbeta chain originated from a pathogenically irrelevant TCR, and the second
      line additionally expresses transgenic TCRalphamini locus. Analysis of TCR
      sequences on NOD background reveals lower TCR diversity on Treg cells not only in
      the thymus, but also in the periphery. This reduction in diversity does not
      affect conventional CD4+ T cells, as compared to the TCRmini repertoire on B6
      background. Interestingly, neither transgenic TCRbeta nor TCRmini mice develop
      diabetes, which we show is due to lack of insulin B:9-23 specific T cells in the
      periphery. Conversely SS develops in both lines, with full glandular
      infiltration, production of autoantibodies and hyposalivation. It shows that SS
      development is not as sensitive to limited availability of TCR specificities as
      T1D, which suggests wider range of possible TCR/peptide/MHC interactions driving
      autoimmunity in SS. 

PMID- 25379764
TI  - [Prolongation of psychiatric training - contra].

PMID- 25379765
TI  - [Obituary for Prof. Bernd Eikelmann, MD].

PMID- 25379766
TI  - [Reports from the Federal Directors Conference (BDK)].

PMID- 25379767
TI  - A review of the literature regarding nutritional supplements and their effect on
      vaginal flora and preterm birth.
AB  - PURPOSE OF REVIEW: The aim of this review was to evaluate recently published
      review articles which examine the use of nutritional supplements to prevent
      preterm birth (PTB) by modifying vaginal bacteria. RECENT FINDINGS: Probiotics,
      vitamin D and vitamin C were all identified as nutritional supplements that have
      the potential to alter bacterial flora and consequently reduce PTB and treat or
      prevent genital infections. Evidence shows that probiotics may reduce the
      incidence of PTB as well as being effective at treating bacterial vaginosis, a
      known cause for PTB. Low vitamin D levels may be associated with bacterial
      vaginosis, although no evidence was identified which demonstrated that vitamin D
      supplementation reduced the risk of having bacterial vaginosis or PTB.There is
      little evidence regarding vitamin C supplementation, although it does suggest a
      possible benefit with regard to preterm rupture of membranes; however, this did
      not appear to reduce rates of PTB. SUMMARY: Although there is evidence that
      taking probiotics in pregnancy may reduce the incidence of PTB, it is mainly
      derived from small, poor quality studies. Vitamin D and vitamin C may have
      potential benefits, but these remain to be proven. Large randomized controlled
      trials are needed to more accurately evaluate the potential benefits of these low
      cost interventions for reducing PTB and its consequences.

PMID- 25379768
TI  - Strong Start for Mothers and Newborns: implications for prenatal care delivery.
AB  - PURPOSE OF REVIEW: In February 2012, the Centers for Medicare and Medicaid
      Services announced a 4-year initiative to test new approaches to prenatal care
      delivery to improve rates of preterm birth for women enrolled in Medicaid. The
      Strong Start for Mothers and Newborns initiative was designed to achieve this
      goal through two strategies: first, a public awareness campaign designed to
      reduce the rate of elective deliveries prior to 39-week gestation, and second, a
      funding opportunity to test the effectiveness of enhanced prenatal care models
      designed to reduce the incidence of low-birth-weight infants among pregnant
      Medicaid beneficiaries. This article reviews previous prenatal care expansion
      efforts and provides insights into the alternative prenatal care delivery models
      currently being tested for low-income patient populations at high risk for
      adverse birth outcomes. RECENT FINDINGS: Alternative prenatal care models, such
      as prenatal home visitation and group prenatal care for patients at high risk for
      adverse birth outcomes, may provide more efficient and effective care than the
      traditional, predominantly medical model of prenatal care delivery. SUMMARY: The
      authors discuss the relationship between prenatal care utilization and adverse
      birth outcomes, such as low birth weight, and current efforts to reinvent
      prenatal care content, structure and delivery.

PMID- 25379769
TI  - Addressing reproductive health disparities as a healthcare management priority:
      pursuing equity in the era of the Affordable Care Act.
AB  - PURPOSE OF REVIEW: To summarize the newest available evidence on maternal and
      reproductive health disparities, and to describe elements of the Affordable Care
      Act most likely to impact these disparities. RECENT FINDINGS: Significant racial
      and ethnic disparities in maternal and reproductive health outcomes have
      persisted in recent years, contributing to poor outcomes and increasing costs.
      Pregnancy-related mortality ratios are up to three times higher in Black women
      compared with non-Hispanic White women, with the risk of severe maternal
      morbidity also significantly higher in Black and Hispanic women. Unintended
      pregnancy is twice as likely in minority women. Insurance status, socioeconomic
      status, and broader social determinants of health are implicated in these
      disparities. Coverage changes associated with the Affordable Care Act may provide
      some opportunities to reach communities most at risk. Delivery innovation,
      payment reform, and further public financing of key services are examples of
      further management approaches that can be used to address reproductive health
      disparities. SUMMARY: The Affordable Care Act offers important opportunities to
      address persistent reproductive health disparities, but significant gaps remain.
      Efforts must be made to reduce the negative outcomes and high financial and human
      costs associated with disparities in reproductive health.

PMID- 25379770
TI  - Stratified reproduction, family planning care and the double edge of history.
AB  - PURPOSE OF REVIEW: There is a growing clinical consensus that Medicaid
      sterilization consent protections should be revisited because they impede desired
      care for many women. Here, we consider the broad social and ideological contexts
      for past sterilization abuses, beyond informed consent. RECENT FINDINGS:
      Throughout the US history, the fertility and childbearing of poor women and women
      of color were not valued equally to those of affluent white women. This is
      evident in a range of practices and policies, including black women's treatment
      during slavery, removal of Native children to off-reservation boarding schools
      and coercive sterilizations of poor white women and women of color. Thus,
      reproductive experiences throughout the US history were stratified. This ideology
      of stratified reproduction persists today in social welfare programs, drug policy
      and programs promoting long-acting reversible contraception. SUMMARY: At their
      core, sterilization abuses reflected an ideology of stratified reproduction, in
      which some women's fertility was devalued compared to other women's fertility.
      Revisiting Medicaid sterilization regulations must therefore put issues of race,
      ethnicity, class, power and resources - not just informed consent - at the center
      of analyses.

PMID- 25379772
TI  - Transport and thermoelectric properties of polyaniline/reduced graphene oxide
      nanocomposites.
AB  - Polyanilines (PANI)/reduced graphene oxide (RGO) nanocomposites are chemically
      synthesized. Their structure and morphology are characterized by scanning and
      transmission electron microscopies, x-ray diffraction and Raman spectroscopy. In
      addition, the nanocomposites' electrical, thermal and thermoelectric (TE)
      transport characteristics are investigated as a function of RGO content. The
      power factor and figure of merit (ZT) of PANI/RGO hybrids are deduced from
      measurements of the electrical conductivity (sigma), Seebeck coefficient (alpha)
      and thermal conductivity (kappa). Experimental results reveal that the properties
      of PANI/RGO composites are inherently dependent on the volume fraction of RGO. It
      is observed that electrical percolation follows a 2D conduction process which
      takes place for samples having 0.099 vol% RGO content. Unlike electrical
      conductivity, the thermal conductivity of PANI/RGO increases only slightly with
      the RGO fraction and is successfully fitted using a modified MG-EMA model which
      provides an interfacial (PANI/RGO nanoplatelets) resistance (Rk) of 4.9 * 10(-10)
      m(2) K W(-1). This low Rk value is attributed to good interactions between the
      planar geometry of RGO platelets and PANI aromatic rings through pi-pi stackings
      as evidenced by Raman spectroscopy and x-ray studies. Compared to that of pure
      PANI, the TE performance of PANI/RGO composites exhibits a ZT enhancement of two
      orders of magnitude.

PMID- 25379773
TI  - Hand hygiene--evaluation of three disinfectant hand sanitizers in a community
      setting.
AB  - Hand hygiene is acknowledged as the single most important measure to prevent
      nosocomial infections in the healthcare setting. Similarly, in non-clinical
      settings, hand hygiene is recognised as a key element in helping prevent the
      spread of infectious diseases. The aim of this study was to evaluate the efficacy
      of three different disinfectant hand sanitizers in reducing the burden of
      bacterial hand contamination in 60 healthy volunteers in a community setting,
      both before and after education about the correct use of hand sanitizers. The
      study is the first to evaluate the efficacy and ease of use of different
      formulations of hand rubs used by the general population. The products tested
      were: Sterillium (perfumed, liquid), desderman pure gel (odorless, gel) and Lavit
      (perfumed, spray). Sterillium and desderman are EN1500 (hygienic hand rub)
      certified products (available in pharmacy) and Lavit is non EN1500 certified and
      available in supermarkets. The two EN1500 certified products were found to be
      significantly superior in terms of reducing bacterial load. desderman pure gel,
      Sterillium and Lavit reduced the bacterial count to 6.4%, 8.2% and 28.0%
      respectively. After education in the correct use of each hand rub, the bacterial
      load was reduced even further, demonstrating the value of education in improving
      hand hygiene. Information about the testers' perceptions of the three sanitizers,
      together with their expectations of a hand sanitizer was obtained through a
      questionnaire. Efficacy, followed by skin compatibility were found to be the two
      most important attributes of a hand disinfectant in our target group. 

PMID- 25379771
TI  - Potential compensation among group I PAK members in hindlimb ischemia and wound
      healing.
AB  - PAKs are serine/threonine kinases that regulate cytoskeletal dynamics and cell
      migration. PAK1 is activated by binding to the small EF hand protein, CIB1, or to
      the Rho GTPases Rac1 or Cdc42. The role of PAK1 in angiogenesis was established
      based only on in vitro studies and its role in angiogenesis in vivo has never
      been examined. Here we tested the hypothesis that PAK1 is an essential regulator
      of ischemic neovascularization (arteriogenesis and angiogenesis) and wound
      healing using a global PAK1 knockout mouse. Neovascularization was assessed using
      unilateral hindlimb ischemia. We found that plantar perfusion, limb use and
      appearance were not significantly different between 6-8 week old PAK1-/- and
      PAK1+/+ mice throughout the 21-day period following hindlimb ischemia; however a
      slightly delayed healing was observed in 16 week old PAK1-/- mice. In addition,
      the wound healing rate, as assessed with an ear punch assay, was unchanged in
      PAK1-/- mice. Surprisingly, however, we observed a notable increase in PAK2
      expression and phosphorylation in ischemic gastrocnemius tissue from PAK1-/- but
      not PAK1+/+ mice. Furthermore, we observed higher levels of activated ERK2, but
      not AKT, in ischemic and non-ischemic muscle of PAK1-/- mice upon hindlimb
      ischemic injury. A group I PAK inhibitor, IPA3, significantly inhibited
      endothelial cell sprouting from aortic rings in both PAK1-/- and PAK1+/+ mice,
      implying that PAK2 is a potential contributor to this process. Taken together,
      our data indicate that while PAK1 has the potential to contribute to
      neovascularization and wound healing, PAK2 may functionally compensate when PAK1
      is deficient. 

PMID- 25379774
TI  - Tuning graft- and host-derived vascularization in modular tissue constructs: a
      potential role of HIF1 activation.
AB  - A better understanding of the factors governing the vascularization of engineered
      tissues is crucial for their advancement as therapeutic platforms. Here, we
      studied the effect of implant volume and cell densities on the in vivo
      vascularization of modular engineered tissue constructs. Sub-millimeter collagen
      modules containing adipose-derived mesenchymal stromal cells (adMSC) and
      enveloped by human umbilical vein endothelial cells (HUVEC) were subcutaneously
      implanted in severe-combined immunodeficient mice with a beige-mutation (SCID-bg)
      mice. Implant volume and cell density was varied relative to a base case, defined
      as a 0.01 mL implant containing 1.5*10(7) adMSC/mL and 3.9*10(6) HUVEC/mL. At 7
      and 14 days post-transplantation, the constructs were harvested for
      immunohistochemical analysis of total (CD31(+)) and graft-derived (UEA1(+))
      vessel formation, hypoxia-inducible factor 1-alpha (HIF1alpha) expression,
      infiltration of host-derived leukocytes (CD45), and macrophages (F4/80). Implant
      volume and cell density affected the relative contributions of host- versus graft
      derived vascularization, highlighting that different mechanisms underlie the two
      processes. Graft-derived vessel formation was most rapid and robust in implants
      with high HIF1alpha expression, namely large volume implants and implants with
      high adMSC and HUVEC density (p<0.01 compared to base case at day 7). Many
      HIF1alpha(+) cells were vessel-lining HUVEC, suggesting that HIF1 activation may
      be key to vessel assembly in the graft. Host vessel ingrowth, however, dominated
      the vascularization of small volume implants (of high and low adMSC density
      alike), which showed low HIF1alpha expression at day 7. Host vessels were
      sustained to day 14 when adMSC density alone was increased, presumably due to
      increased paracrine secretions. This study points to a potential role of HIF1
      activation in the vascularization of tissue constructs, which may be harnessed to
      engineer robust vessels for therapeutic applications.

PMID- 25379775
TI  - Spatial temperature mapping within polymer nanocomposites undergoing ultrafast
      photothermal heating via gold nanorods.
AB  - Heat emanates from gold nanorods (GNRs) under ultrafast optical excitation of the
      localized surface plasmon resonance. The steady state nanoscale temperature
      distribution formed within a polymer matrix embedded with GNRs undergoing pulsed
      femtosecond photothermal heating is determined experimentally using two
      independent ensemble optical techniques. Physical rotation of the nanorods
      reveals the average local temperature of the polymer melt in the immediate
      spatial volume surrounding each rod while fluorescence of homogeneously
      distributed perylene molecules monitors temperature over sample regions at larger
      distances from the GNRs. Polarization-sensitive fluorescence measurements of the
      perylene probes provide an estimate of the average size of the quasi-molten
      region surrounding each nanorod (that is, the boundary between softened polymer
      and solid material as the temperature decreases radially away from each particle)
      and distinguishes the steady state temperature in the solid and melt regions.
      Combining these separate methods enables nanoscale spatial mapping of the average
      steady state temperature distribution caused by ultrafast excitation of the GNRs.
      These observations definitively demonstrate the presence of a steady-state
      temperature gradient and indicate that localized heating via the photothermal
      effect within materials enables nanoscale thermal manipulations without
      significantly altering the bulk sample temperature in these systems. These
      quantitative results are further verified by re-orienting nanorods within a solid
      polymer nanofiber without inducing any morphological changes to the highly
      temperature-sensitive nanofiber surface. Temperature differences of 70-90 
      degrees C were observed over a distances of ~ 100 nm.

PMID- 25379776
TI  - Facilely synthesized benzotriazole phenolate zirconium complexes as versatile
      catalysts for copolymerization of carbon dioxide with cyclohexene oxide and
      lactide polymerization.
AB  - A family of zirconium complexes containing bis-, tri- or tetra-BTP ligands (BTP =
      benzotriazole phenolate) were synthesized and structurally characterized.
      Treatment of Zr(O(i)Pr)4((i)PrOH) with 2.0 molar equivalents of 2-(2H
      benzotriazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)phenol ((C8)BTP-H) or 2-(2H
      benzotriazol-2-yl)-4,6-di-tert-butylphenol ((t-Bu)BTP-H) afforded zirconium
      alkoxide ([((C8)BTP)2Zr(O(i)Pr)2] (1); [((t-Bu)BTP)2Zr(O(i)Pr)2] (2)) in good
      yield. Similarly, the bis-adduct Zr amide [((t-Bu)BTP)2Zr(NMe2)2] (3) resulted
      from amine elimination of Zr(NMe2)4 as the metal precursor and (t-Bu)BTP-H as the
      pro-ligand under a similar synthetic method with a metal to ligand precursor
      ratio of 1:2 at 0  degrees C. The reaction of Zr(NMe2)4 with (C8)BTP-H or (t
      Bu)BTP-H (4.0 mol equiv.) gave the tetra-adduct zirconium complex ([((C8)BTP)4Zr]
      (4); [((t-Bu)BTP)4Zr] (5)) in ?70% yield. Interestingly, the tri-adduct Zr amide
      [((t-Bu)BTP)3Zr(NMe2)] (6) could be prepared by treatment of 3 with a
      stoichiometric amount of (t-Bu)BTP-H. The solid-state structure of 6 reveals a
      monomeric Zr(IV) amide with three (t-Bu)BTP ligands and one -NMe2 group, and the
      bonding modes between the BTP moiety and the metal centre adopt both N,O
      bidentate and O-monodentate types. Zr complexes 1 and 4 incorporating sterically
      less bulky (C8)BTP ligands were demonstrated to efficiently catalyse not only
      copolymerization of epoxide with CO2 but also lactide polymerization. The tetra
      BTP Zr catalyst 4 was able to copolymerize cyclohexene oxide and CO2 in a
      controllable manner, generating the high-molecular-weight copolymer (Mw > 10,000
      g mol(-1)) and a high degree of carbonate linkages (>90%). Single-site zirconium
      alkoxide 1 is the most active catalyst for living lactide polymerization in
      solution among these complexes, giving poly(lactide)s with the expected molecular
      weights and narrow molecular weight distributions (PDI ? 1.25). This is a
      successful example of utilizing versatile benzotriazole phenolate Zr(IV)
      catalysts for either the production of biodegradable poly(lactide) or
      poly(cyclohexene carbonate-co-cyclohexene oxide).

PMID- 25379777
TI  - Discrimination of complex human behavior by pigeons (Columba livia) and humans.
AB  - The cognitive and neural mechanisms for recognizing and categorizing behavior are
      not well understood in non-human animals. In the current experiments, pigeons and
      humans learned to categorize two non-repeating, complex human behaviors ("martial
      arts" vs. "Indian dance"). Using multiple video exemplars of a digital human
      model, pigeons discriminated these behaviors in a go/no-go task and humans in a
      choice task. Experiment 1 found that pigeons already experienced with
      discriminating the locomotive actions of digital animals acquired the
      discrimination more rapidly when action information was available than when only
      pose information was available. Experiments 2 and 3 found this same dynamic
      superiority effect with naive pigeons and human participants. Both species used
      the same combination of immediately available static pose information and more
      slowly perceived dynamic action cues to discriminate the behavioral categories.
      Theories based on generalized visual mechanisms, as opposed to embodied, species
      specific action networks, offer a parsimonious account of how these different
      animals recognize behavior across and within species. 

PMID- 25379779
TI  - Hydrogen storage in platinum decorated hydrogen exfoliated graphene sheets by
      spillover mechanism.
AB  - Development of lightweight materials with high hydrogen storage capacities is a
      great challenge for the hydrogen economy. Here, we report high pressure hydrogen
      adsorption-desorption studies of platinum-decorated hydrogen-exfoliated graphene
      sheets (Pt-HEG). Pt-HEG shows a maximum hydrogen uptake capacity of 1.4 wt% at 25
      degrees C and 3 MPa. Analysis of the isosteric heat of adsorption provides
      evidence of spillover mechanism. 

PMID- 25379778
TI  - Variability in vulnerability assessment of older people by individual general
      practitioners: a cross-sectional study.
AB  - BACKGROUND: In clinical practice, GPs appeared to have an internalized concept of
      "vulnerability." This study investigates the variability between general
      practitioners (GPs) in their vulnerability-assessment of older persons. METHODS:
      Seventy-seven GPs categorized their 75-plus patients (n = 11392) into non
      vulnerable, possibly vulnerable, and vulnerable patients. GPs personal and
      practice characteristics were collected. From a sample of 2828 patients the
      following domains were recorded: sociodemographic, functional [instrumental
      activities in daily living (IADL), basic activities in daily living (BADL)],
      somatic (number of diseases, polypharmacy), psychological (Mini-Mental State
      Examination, 15-item Geriatric Depression Scale; GDS-15) and social (De Jong
      Gierveld Loneliness Scale; DJG). Variability in GPs' assessment of vulnerability
      was tested with mixed effects logistic regression. P-values for variability
      (pvar) were calculated by the log-likelihood ratio test. RESULTS: Participating
      GPs assessed the vulnerability of 10,361 patients. The median percentage of
      vulnerable patients was 32.0% (IQR 19.5 to 40.1%). From the somatic and
      psychological domains, GPs uniformly took into account the patient
      characteristics 'total number of diseases' (OR 1.7, 90% range  = 0, p var = 1),
      'polypharmacy' (OR 2.3, 90% range  = 0, p var = 1) and 'GDS-15' (OR 1.6, 90%
      range  = 0, p var = 1). GPs vary in the way they assessed their patients'
      vulnerability in the functional domain (IADL: median OR 2.8, 90% range 1.6, p var
      < 0.001, BADL: median OR 2.4, 90% range 2.9, p var < 0.001) and the social domain
      (DJG: median OR 1.2, 90% range  = 1.2, p var < 0.001). CONCLUSIONS: GPs seem to
      share a medical concept of vulnerability, since they take somatic and
      psychological characteristics uniformly into account in the vulnerability
      assessment of older persons. In the functional and social domains, however,
      variability was found. Vulnerability assessment by GPs might be a promising
      instrument to select older people for geriatric care if more uniformity could be
      achieved. TRIAL REGISTRATION: Netherlands Trial Register NTR1946.

PMID- 25379781
TI  - Taurolidine lock is superior to heparin lock in the prevention of catheter
      related bloodstream infections and occlusions.
AB  - BACKGROUND AND AIMS: Patients on home parenteral nutrition (HPN) are at risk for
      catheter-related complications; mainly infections and occlusions. We have
      previously shown in HPN patients presenting with catheter sepsis that catheter
      locking with taurolidine dramatically reduced re-infections when compared with
      heparin. Our HPN population therefore switched from heparin to taurolidine in
      2008. The aim of the present study was to compare long-term effects of this
      catheter lock strategy on the occurrence of catheter-related bloodstream
      infections and occlusions in HPN patients. METHODS: Data of catheter-related
      complications were retrospectively collected from 212 patients who received HPN
      between January 2000 and November 2011, comprising 545 and 200 catheters during
      catheter lock therapy with heparin and taurolidine, respectively. We evaluated
      catheter-related bloodstream infection and occlusion incidence rates using
      Poisson-normal regression analysis. Incidence rate ratios were calculated by
      dividing incidence rates of heparin by those of taurolidine, adjusting for
      underlying disease, use of anticoagulants or immune suppressives, frequency of
      HPN/fluid administration, composition of infusion fluids, and duration of
      HPN/fluid use before catheter creation. RESULTS: Bloodstream infection incidence
      rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters.
      Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine
      locked catheters. Adjusted incidence ratios of heparin compared to taurolidine
      were 5.9 (95% confidence interval, 3.9-8.7) for bloodstream infections and 1.9
      (95% confidence interval, 1.1-3.1) for occlusions. CONCLUSIONS: Given that no
      other procedural changes than the catheter lock strategy were implemented during
      the observation period, these data strongly suggest that taurolidine decreases
      catheter-related bloodstream infections and occlusions in HPN patients compared
      with heparin.

PMID- 25379783
TI  - Thymus vulgaris (thyme) inhibits proliferation, adhesion, migration, and invasion
      of human colorectal cancer cells.
AB  - Colorectal cancer (CRC) remains one of the most common malignancies and a leading
      cause of cancer-related deaths. Its prognosis remains poor for patients with
      several grades of this disease. This underscores the need for alternative
      modalities, such as herbal medicines, to treat this disease. A commonly used
      plant that appears to be of high medicinal value is Thymus vulgaris L. However,
      the effects of this plant on the malignant behavior of human CRC cells remains
      poorly investigated. This study was undertaken to determine the anticancer
      efficacy of T. vulgaris extract (TVE) in CRC cells. Our results show that TVE
      inhibits proliferation in a concentration- and time-dependent fashion. This
      decreased proliferation was concomitant with increased apoptotic cell death as
      evidenced by increased caspase3/7 activity. Moreover, TVE also decreased adhesion
      to fibronectin in a concentration-dependent manner. The migratory and invasive
      capacities of HCT116 cells were significantly inhibited by TVE. Taken together,
      these data suggest that the TVE inhibits malignant phenotype of colon cancer
      cells. Therefore, T. vulgaris could have an anticancer effect and that some of
      its bioactive compounds may prove to be effective treatment modalities for human
      CRC.

PMID- 25379784
TI  - Tetraiodoethynyl resorcinarene cavitands as multivalent halogen bond donors.
AB  - The syntheses and halogen bonded (XB) complexes of tetrahalogenated ethynyl
      cavitands are presented. These cavitands act as quite rigid 3D multivalent
      halogen bond donors and show strong XB with oxygen, nitrogen and bromide XB
      acceptors. 

PMID- 25379782
TI  - Development of quantitative proteomics using iTRAQ based on the immunological
      response of Galleria mellonella larvae challenged with Fusarium oxysporum
      microconidia.
AB  - Galleria mellonella has emerged as a potential invertebrate model for
      scrutinizing innate immunity. Larvae are easy to handle in host-pathogen assays.
      We undertook proteomics research in order to understand immune response in a
      heterologous host when challenged with microconidia of Fusarium oxysporum. The
      aim of this study was to investigate hemolymph proteins that were differentially
      expressed between control and immunized larvae sets, tested with F. oxysporum at
      two temperatures. The iTRAQ approach allowed us to observe the effects of immune
      challenges in a lucid and robust manner, identifying more than 50 proteins, 17 of
      them probably involved in the immune response. Changes in protein expression were
      statistically significant, especially when temperature was increased because this
      was notoriously affected by F. oxysporum 104 or 106 microconidia/mL. Some
      proteins were up-regulated upon immune fungal microconidia challenge when
      temperature changed from 25 to 37 degrees C. After analysis of identified
      proteins by bioinformatics and meta-analysis, results revealed that they were
      involved in transport, immune response, storage, oxide-reduction and catabolism:
      20 from G. mellonella, 20 from the Lepidoptera species and 19 spread across
      bacteria, protista, fungi and animal species. Among these, 13 proteins and 2
      peptides were examined for their immune expression, and the hypothetical 3D
      structures of 2 well-known proteins, unannotated for G. mellonella, i.e., actin
      and CREBP, were resolved using peptides matched with Bombyx mori and Danaus
      plexippus, respectively. The main conclusion in this study was that iTRAQ tool
      constitutes a consistent method to detect proteins associated with the innate
      immune system of G. mellonella in response to infection caused by F. oxysporum.
      In addition, iTRAQ was a reliable quantitative proteomic approach to detect and
      quantify the expression levels of immune system proteins and peptides, in
      particular, it was found that 104 microconidia/mL at 37 degrees C over expressed
      many more proteins than other treatments. 

PMID- 25379785
TI  - Spatial segregation between invasive and native commensal rodents in an urban
      environment: a case study in Niamey, Niger.
AB  - Invasive rodents have been responsible for the diffusion worldwide of many
      zoonotic agents, thus representing major threats for public health. Cities are
      important hubs for people and goods exchange and are thus expected to play a
      pivotal role in invasive commensal rodent dissemination. Yet, data about urban
      rodents' ecology, especially invasive vs. native species interactions, are
      dramatically scarce. Here, we provide results of an extensive survey of urban
      rodents conducted in Niamey, Niger, depicting the early stages of rodent
      bioinvasions within a city. We explore the species-specific spatial distributions
      throughout the city using contrasted approaches, namely field sampling, co
      occurrence analysis, occupancy modelling and indicator geostatistics. We show
      that (i) two species (i.e. rural-like vs. truly commensal) assemblages can be
      identified, and that (ii) within commensal rodents, invasive (Rattus rattus and
      Mus musculus) and native (Mastomys natalensis) species are spatially segregated.
      Moreover, several pieces of arguments tend to suggest that these exclusive
      distributions reflect an ongoing native-to-invasive species turn over. The
      underlying processes as well as the possible consequences for humans are
      discussed. 

PMID- 25379786
TI  - Asymmetric synthesis of tetrahydropyridines via an organocatalytic one-pot
      multicomponent Michael/aza-Henry/cyclization triple domino reaction.
AB  - A low loading of a quinine-derived squaramide efficiently catalyzes the triple
      domino Michael/aza-Henry/cyclization reaction between 1,3-dicarbonyl compounds,
      beta-nitroolefins, and aldimines to provide tetrahydropyridines bearing three
      contiguous stereogenic centers in good yields, excellent enantiomeric excesses,
      and up to high diastereomeric ratios. 

PMID- 25379787
TI  - One-step click engineering considerably ameliorates the practicality of an
      unqualified rhodamine probe.
AB  - This study describes the exploitation of click chemistry in the one-step
      molecular engineering of an unqualified rhodamine probe, leading to its
      considerable functional enhancement in terms of water solubility, ion
      selectivity, and usefulness in detecting biological and environmental samples. A
      dipropargyl rhodamine dye previously identified as an unselective and poorly
      water-soluble mercury(II) probe was used to couple with an azido polyethylene
      glycol (PEG) by the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition click
      reaction in almost quantitative yield. The simple click-engineered rhodamine
      probe shows, remarkably, better water solubility and mercury(II) selectivity
      comparing to the raw counterpart, and can be used to sensitively image mercury
      ions internalized by live cells and to accurately quantify the ion spiked in
      river water specimens. This study provides insights into the simple functional
      improvement of unqualified molecular dye probes via the efficient "click
      engineering". 

PMID- 25379788
TI  - Technical tips and troubleshooting of endoscopic biliary drainage for
      unresectable malignant hilar biliary obstruction.
AB  - Unresectable malignant hilar biliary obstruction (MHBO) occurs in various
      diseases, such as cholangiocarcinoma, gallbladder carcinoma, hepatocellular
      carcinoma, pancreatic cancer, and lymph node metastasis of the hilum of the
      liver. The majority of patients with advanced MHBO are not candidates for
      surgical resection because of the tumor location in the hepatic hilum and
      adjacent areas, advanced tumor stage, or comorbidities. Therefore, these patients
      often have a poor prognosis in terms of survival and quality of life. Most of
      these patients will require non-surgical, palliative biliary drainage. To date,
      various biliary drainage techniques for unresectable MHBO (UMHBO) have been
      reported. Of these techniques, endoscopic biliary drainage is currently
      considered to be the most safe and minimally invasive procedure. However,
      endoscopic biliary drainage for UMHBO is still not standardized regarding the
      optimal stent, drainage area, stenting method, and reintervention technique.
      Recently, towards standardization of this technique for UMHBO, clinical research
      and trials including randomized controlled trials have been performed. In this
      article, we reviewed the most important issues regarding endoscopic biliary
      drainage for UMHBO, focusing on prospective studies. We also described in detail
      the techniques and future perspectives of endoscopic biliary drainage in patients
      with UMHBO. 

PMID- 25379790
TI  - Positive effects of non-native grasses on the growth of a native annual in a
      southern california ecosystem.
AB  - Fire disturbance is considered a major factor in the promotion of non-native
      plant species. Non-native grasses are adapted to fire and can alter environmental
      conditions and reduce resource availability in native coastal sage scrub and
      chaparral communities of southern California. In these communities persistence of
      non-native grasses following fire can inhibit establishment and growth of woody
      species. This may allow certain native herbaceous species to colonize and persist
      beneath gaps in the canopy. A field manipulative experiment with control, litter,
      and bare ground treatments was used to examine the impact of non-native grasses
      on growth and establishment of a native herbaceous species, Cryptantha muricata.
      C. muricata seedling survival, growth, and reproduction were greatest in the
      control treatment where non-native grasses were present. C. muricata plants
      growing in the presence of non-native grasses produced more than twice the number
      of flowers and more than twice the reproductive biomass of plants growing in the
      treatments where non-native grasses were removed. Total biomass and number of
      fruits were also greater in the plants growing in the presence of non-native
      grasses. Total biomass and reproductive biomass was also greater in late
      germinants than early germinants growing in the presence of non-native grasses.
      This study suggests a potential positive effect of non-native grasses on the
      performance of a particular native annual in a southern California ecosystem. 

PMID- 25379791
TI  - Asymmetric fluorocyclizations of alkenes.
AB  - CONSPECTUS: The vicinal fluorofunctionalization of alkenes is an attractive
      transformation that converts feedstock olefins into valuable cyclic fluorinated
      molecules for application in the pharmaceutical, agrochemical, medical, and
      material sectors. The challenges associated with asymmetric fluorocyclizations
      induced by F(+) reagents are distinct from other types of halocyclizations.
      Processes initiated by the addition of an F(+) reagent onto an alkene do not
      involve the reversible formation of bridged fluoronium ions but generate acyclic
      beta-fluorocationic intermediates. This mechanistic feature implies that
      fluorocyclizations are not stereospecific. A discontinuity exists between the
      importance of this class of fluorocyclization and the activation modes currently
      available to implement successful catalysis. Progress toward fluorocyclization
      has been achieved by investing in neutral and cationic [NF] reagent development.
      The body of work on asymmetric fluorination using chiral cationic [NF](+)
      reagents prepared by fluorine transfer from the dicationic [NF](2+) reagent
      Selectfluor to quinuclidines, inspired the development of asymmetric F(+)-induced
      fluorocyclizations catalyzed by cinchona alkaloids; for catalysis, the use of N
      fluorobenzenesulfonimide, which is less reactive than Selectfluor, ensures that
      the achiral F(+) source remains unreactive toward the alkene. These
      organocatalyzed enantioselective fluorocyclizations can be applied to indoles to
      install the fluorine on a quaternary benzylic stereogenic carbon center and to
      afford fluorinated analogues of natural products featuring the
      hexahydropyrrolo[2,3-b]indole or the tetrahydro-2H-furo[2,3-b]indole skeleton. In
      an alternative approach, the poor solubility of dicationic Selectfluor
      bis(tetrafluoroborate) in nonpolar solvent was exploited with anionic phase
      transfer catalysis as the operating activation mode. Exchange of the
      tetrafluoroborate ions of Selectfluor with bulky lipophilic chiral anions (e.g.,
      TRIP and derivatives) brings into solution the resulting chiral Selectfluor
      reagent, now capable of asymmetric fluorocyclization. This strategy is best
      applied to a subset of substrates bearing a nucleophilic pendent group (benzamide
      is best) capable of hydrogen bonding for association with the chiral phosphate
      catalyst. These contributions focused on fluoroheterocyclization involving either
      O- or N-nucleophiles. As for other halocyclizations, alkenes armed with pi C
      nucleophiles represent the most demanding class of substrates for asymmetric F(+)
      induced electrophilic fluorination-cyclization. Successful implementation
      required the design of new chiral Selectfluor reagents featuring stereogenicity
      on the DABCO core. These reagents, accessible from chiral vicinal diamines,
      allowed the synthesis of unusual chiral fluorine-containing tetracyclic
      compounds, some composed of carbon, hydrogen, and fluorine exclusively. The
      challenges associated with F(+)-induced fluorocarbocyclizations prompted
      methodologists to consider chemistry where the Csp(3)-F bond formation event
      follows a catalyst-controlled cyclization. An exciting development built on in
      the area of transition metal pi-cyclization of polyenes leading to cationic metal
      alkyl intermediates. When intercepted by oxidative fluorodemetalation with a F(+)
      source, the resulting products are complex polycyclic structures emerging from an
      overall catalytic cascade fluorocarbocyclization. Complementing F(+)-based
      reactions, examples of fluorocyclizations with fluoride in the presence of an
      oxidant were reported. Despite some exciting developments, the field of
      asymmetric fluorocyclizations is in its infancy and undoubtedly requires new
      activation modes, catalysts, as well as F(+) and F(-) reagents to progress into
      general retrosynthetic approach toward enantioenriched fluorocycles. Numerous
      opportunities emerge, not least the use of a latent fluorine source as a means to
      minimize background fluorination.

PMID- 25379789
TI  - Calcium-sensing receptor-mediated osteogenic and early-stage neurogenic
      differentiation in umbilical cord matrix mesenchymal stem cells from a large
      animal model.
AB  - BACKGROUND: Umbilical cord matrix mesenchymal stem cells (UCM-MSCs) present a
      wide range of potential therapeutical applications. The extracellular calcium
      sensing receptor (CaSR) regulates physiological and pathological processes. We
      investigated, in a large animal model, the involvement of CaSR in triggering
      osteogenic and neurogenic differentiation of two size-sieved UCM-MSC lines, by
      using AMG641, a novel potent research calcimimetic acting as CaSR agonist.
      METHODOLOGY/PRINCIPAL FINDINGS: Large (>8 um in diameter) and small (<8 um)
      equine UCM-MSC lines were cultured in medium with high calcium (Ca2+)
      concentration ([Ca2+]o; 2.87 mM) and dose-response effects of AMG641 (0.01 to
      3uM) on cell proliferation were evaluated. Both cell lines were then cultured in
      osteogenic or neurogenic differentiation medium containing: 1) low [Ca2+]o (0.37
      mM); 2) high [Ca2+]o (2.87 mM); 3) AMG641 (0.05, 0.1 or 1 uM) with high [Ca2+]o
      and 4) the CaSR antagonist NPS2390 (10 mM for 30 min) followed by incubation with
      AMG641 in high [Ca2+]o. Expression of osteogenic or neurogenic differentiation
      biomarkers was compared among groups. In both cell lines, AMG641 dose-dependently
      increased cell proliferation (up to P<0.001). Osteogenic molecular markers
      expression was differentially regulated by AMG641, with stimulatory (OPN up
      regulation) in large or inhibitory (RUNX2 and OPN down-regulation) effects in
      small cells, respectively. AMG641 significantly increased alkaline phosphatase
      activity and calcium phosphate deposition in both cell lines. Following treatment
      with AMG641 during osteogenic differentiation, in both cell lines CaSR expression
      was inversely related to that of osteogenic markers and inhibition of CaSR by
      NPS2390 blocked AMG641-dependent responses. Early-stage neurogenic
      differentiation was promoted/triggered by AMG641 in both cell lines, as Nestin
      and CaSR mRNA transcription up-regulation were observed.
      CONCLUSIONS/SIGNIFICANCE: Calcium- and AMG641-induced CaSR stimulation promoted
      in vitro proliferation and osteogenic and early-stage neurogenic differentiation
      of UCM-MSCs. CaSR activation may play a fundamental role in selecting specific
      differentiation checkpoints of these two differentiation routes, as related to
      cell commitment status.

PMID- 25379792
TI  - Suicide cases and venlafaxine.

PMID- 25379793
TI  - Relationship between heart rate variability and the severity of psychotic
      symptoms in schizophrenia.

PMID- 25379794
TI  - Sleep disturbance in mild cognitive impairment: differential effects of current
      and remitted depression.

PMID- 25379795
TI  - Escitalopram oxalate, a selective serotonin reuptake inhibitor, exhibits
      cytotoxic and apoptotic effects in glioma C6 cells.

PMID- 25379796
TI  - Paliperidone in the treatment of delirium: results of a prospective open-label
      pilot trial.

PMID- 25379797
TI  - The neurophilosophy of epileptic experiences.

PMID- 25379798
TI  - Aripiprazole-induced tardive dyskinesia treated with quetiapine: a case report.

PMID- 25379799
TI  - Low-dose clozapine monotherapy for recurring episodes of depression, hypersomnia
      and behavioural disturbances: a case report.

PMID- 25379800
TI  - Thorough QT studies: are we off target?

PMID- 25379801
TI  - The complete mitochondrial genome sequence of the prostate adenocarcinoma rat
      R3327.
AB  - The prostate adenocarcinoma of the Copenhagen rat (R3327) is recognized as a
      suitable model for human prostate carcinoma. In this study, we sequenced its
      complete mitogenome and total length of the genome was 16,310 bp (GenBank
      Accession Number KM820831). It contains 13 protein-coding genes, 2 ribosomal RNA
      genes, and 22 transfer RNA genes. This mitochondrial genome sequence will provide
      new genetic resource into prostate adenocarcinoma disease.

PMID- 25379802
TI  - Mitochondrial genome of a multiple myeloma bone cancer disease model rat strain
      (Muridae; Rattus).
AB  - We sequenced the complete mitochondrial genome sequencing of a multiple myeloma
      bone cancer disease model rat strain for the first time. The total length of the
      mitogenome was 16,302 bp and coding 13 protein-coding genes, two ribosomal RNA
      genes, 22 transfer RNA genes.

PMID- 25379803
TI  - Evaluation of Choroidal Thickness in Amblyopia Using Enhanced Depth Imaging
      Optical Coherence Tomography.
AB  - PURPOSE: To evaluate the choroidal thickness (CT) in hyperopic anisometropic
      amblyopic eyes, fellow non-amblyopic eyes, and age-matched normal eyes, using
      spectral-domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: In
      total 53 subjects (17.8 +/- 11.0 years, mean +/- SD) with hyperopic anisometropic
      amblyopia (AE) and 53 age-matched controls (17.7 +/- 11.0 years) were included in
      this prospective study. Each subject underwent a dilated eye examination,
      cycloplegic refraction and axial length (AL) measurement using Nidek AL-Scan
      optical biometer (Nidek CO, Aichi, Japan). The CT of subfoveal area and at a
      radius of 1 and 3 mm around the fovea was determined using the enhanced depth
      imaging program of a SD-OCT (Cirrus HD OCT, Carl-Zeiss Meditec, Dublin, CA). CT,
      AL and spherical equivalent refraction (SER) of the amblyopic eyes were compared
      to that of the fellow and control eyes. RESULTS: The mean subfoveal CT was 305.6
      +/- 26.0 um in the amblyopic eyes, 282.6 +/- 30.7 um in the fellow eyes and 280.1
      +/- 8.8 in the control eyes. The subfoveal choroid in amblyopic eyes was
      significantly thicker than that of the fellow eyes and control eyes (p <  0.001).
      There was a significant negative correlation between the subfoveal CT and the AL
      in amblyopic (r = -0.298, p=0.03) eyes but not in the control and fellow eyes.
      CONCLUSIONS: The subfoveal choroid of eyes with hyperopic AE is significantly
      thicker than that of the fellow eye and the age-matched controls. Hence, CT seems
      to be effected in AE.

PMID- 25379805
TI  - Elastic liposome-based gel for topical delivery of 5-fluorouracil: in vitro and
      in vivo investigation.
AB  - OBJECTIVE: This investigation has focused to characterize the elastic liposome
      containing 5-fluorouracil (5-FU) and to enhance drug permeation across stratum
      corneum (SC) of the skin (rat) using various surfactants and in vivo dermal
      toxicity evaluation. METHODOLOGY: 5-FU-loaded elastic liposomes were developed,
      prepared and characterized for their entrapment efficiency, vesicle size, number
      of vesicles, morphological characteristics, surface charge and turbidity. In
      vitro drug release profile, in vitro skin permeation potential and in vitro
      hemolytic ability of the formulation have been evaluated to compare with drug
      solution for 24 h. In vitro skin permeation potential was also compared with
      marketed cream. Furthermore, in vivo skin irritation potential, drug penetration
      into the skin using confocal laser scanning microscopy (CLSM) and in vivo
      toxicity studies were performed. RESULTS AND CONCLUSIONS: The optimized elastic
      liposomes demonstrated maximum drug entrapment efficiency, optimum vesicular size
      and considerable elasticity. In vitro skin permeation studies showed the highest
      drug permeation flux like 77.07 +/- 6.34, 89.74 +/- 8.5 and 70.90 +/- 9.6
      ug/cm(2)/h for EL3-S60, EL3-S80 and EL3-T80, respectively, as compared to drug
      solution (8.958 +/- 6.9 ug/cm(2)/h) and liposome (36.80 +/- 6.4 ug/cm(2)/h). Drug
      deposition of optimized elastic liposome EL3-S80 was about three fold higher than
      drug solution. Skin irritation and CLSM studies suggested that optimized gel was
      free from skin irritation and capable to deliver 5-FU into the epidermal area for
      enhanced topical delivery than drug solution. The in vitro study showed minimum
      hemolysis in the optimized formulation. Finally, in vivo toxicity studies
      followed with hisptopathological assessment showed that elastic liposome was able
      to extract SC to improve drug permeation without changing general anatomy of the
      skin.

PMID- 25379804
TI  - Intestinal colonization by Candida albicans alters inflammatory responses in
      Bruton's tyrosine kinase-deficient mice.
AB  - The commensal yeast Candida albicans is part of the human intestinal microflora
      and is considered a "pathobiont", a resident microbe with pathogenic potential
      yet harmless under normal conditions. The aim of this study was to investigate
      the effect of C. albicans on inflammation of the intestinal tract and the role of
      Bruton's tyrosine kinase (Btk). Btk is an enzyme that modulates downstream
      signaling of multiple receptors involved in innate and adaptive immunity,
      including the major anti-fungal receptor Dectin-1. Colitis was induced in wild
      type and Btk-/- mice by treatment with dextran sodium sulfate (DSS) and the
      gastrointestinal tract of selected treatment groups were then colonized with C.
      albicans. Colonization by C. albicans neither dampened nor exacerbated
      inflammation in wild type mice, but colon length and spleen weight were improved
      in Btk-deficient mice colonized with C. albicans. Neutrophil infiltration was
      comparable between wild type and Btk-/- mice, but the knockout mice displayed
      severely reduced numbers of macrophages in the colon during both DSS and
      DSS/Candida treatment. Smaller numbers and reduced responsiveness of Btk-/-
      macrophages might partially explain the improved colon length of Btk-/- mice as a
      result of Candida colonization. Surprisingly, DSS/Candida-treated Btk-/- animals
      had higher levels of certain pro-inflammatory cytokines and levels of the anti
      inflammatory cytokine TGF-beta were reduced compared to wild type. A clustering
      and correlation analysis showed that for wild type animals, spleen TGF-beta and
      colon IL-10 and for Btk-/- spleen and colon levels of IL-17A best correlated with
      the inflammatory parameters. We conclude that in Btk-/- immunocompromised
      animals, colonization of the gastrointestinal tract by the commensal yeast C.
      albicans alters inflammatory symptoms associated with colitis. 

PMID- 25379806
TI  - Development, optimization and characterization of glycyrrhetinic acid-chitosan
      nanoparticles of atorvastatin for liver targeting.
AB  - Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-targeted
      carrier for drug delivery. In this study, nanoparticles were prepared by ionic
      gelation process, and glycyrrhetinic acid act as the targeting ligand. The
      structure of the product was confirmed by IR and NMR techniques. The main aim of
      this study was to deliver atorvastatin directly to the liver by using same
      conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high
      dose. Characterization of the developed formulation was performed by differential
      scanning calorimetry, particle size measurements and cellular uptake studies.
      Release profile, pharmacokinetics studies and organ distribution studies showed
      that developed formulation shows a relative higher liver uptake. The optimized
      formulation showed increased plasma concentration than the CTS nanoparticles as
      well as plain drug and the accumulation in the liver was nearly 2.59 times more
      than that of obtained with the CTS nanoparticles. Pharmaceutical and
      pharmacological indicators suggested that the proposed strategy can be
      successfully utilized for liver targeting of therapeutics.

PMID- 25379807
TI  - Disordered Atom Molecular Potential for Water Parameterized against Neutron
      Diffraction Data. Application to the Structure of Ice Ih.
AB  - A disordered atom molecular potential (DAMP) for water is described that
      accurately accounts for the observed neutron interference differential scattering
      cross sections for light water, heavy water, and two different mixtures of these
      liquids (x = 0.5 and x = 0.64, where x is the mole fraction of light water in the
      mixtures) at T = 283 K. This potential, when used in a NVT Monte Carlo computer
      simulation, produces an intermolecular pressure of ~0 kbar and a configurational
      energy of approximately -50 kJ/mol, close to the values found in the ambient
      liquid at this temperature. The same potential is used as the reference potential
      in an empirical potential structure refinement of ice diffraction data at T = 258
      K measured at the same time as the water data and under the same conditions.
      Particularly intriguing is the finding that the O...O-H angle in ice, which would
      be 0 degrees  for a linear hydrogen bond, is actually more disordered in ice than
      in the liquid. A rationalization of these findings is presented. It remains to be
      seen whether this potential has any value other than simply as a description of
      the ambient liquid structure. 

PMID- 25379808
TI  - Catalytic Z-selective cross-metathesis in complex molecule synthesis: a
      convergent stereoselective route to disorazole C1.
AB  - A convergent diastereo- and enantioselective total synthesis of anticancer and
      antifungal macrocyclic natural product disorazole C1 is reported. The central
      feature of the successful route is the application of catalytic Z-selective cross
      metathesis (CM). Specifically, we illustrate that catalyst-controlled
      stereoselective CM can be performed to afford structurally complex Z-alkenyl
      B(pin) as well as Z-alkenyl iodide compounds reliably, efficiently, and with high
      selectivity (pin = pinacolato). The resulting intermediates are then joined in a
      single-step operation through catalytic inter- and intramolecular cross-coupling
      to furnish the desired 30-membered ring macrocycle containing the critical
      (Z,Z,E)-triene moieties. 

PMID- 25379812
TI  - Examining the contextual and temporal stability of perceptions of emotional
      utility.
AB  - The present research examined the degree to which perceptions of emotional
      utility are stable across contexts and over time. Self-reported perceptions of
      emotional utility and actual experience of emotion were measured in two samples
      of college students. In Study 1, participants were presented with two different
      types of goals (independent vs. interdependent) and were asked to rate the degree
      to which they found different types of emotions (e.g., appreciation, pride)
      useful in each context. In Study 2, participants completed daily online
      questionnaires in which they responded to questions assessing perceptions of
      emotional utility and actual affect in relation to personal goals. As predicted,
      across both samples, perceived utility of specific types of emotions was found to
      be associated with specific types of goals. Importantly, perceived utility of
      emotion was also found to be a relatively stable individual difference variable,
      even after taking into account the actual experience of emotion. 

PMID- 25379809
TI  - High utility of contact investigation for latent and active tuberculosis case
      detection among the contacts: a retrospective cohort study in Tbilisi, Georgia,
      2010-2011.
AB  - SETTING: The study was conducted at the National Center for Tuberculosis and Lung
      Diseases (NCTBLD) in Tbilisi, Georgia. OBJECTIVE: To assess the utility of
      contact investigation for tuberculosis (TB) case detection. We also assessed the
      prevalence and risk factors for active TB disease and latent TB infection (LTBI)
      among contacts of active pulmonary TB cases. DESIGN: A retrospective cohort study
      was conducted among the contacts of active pulmonary TB cases registered in 2010
      2011 at the NCTBLD in Tbilisi, Georgia. Contacts of active TB patients were
      investigated according to an "invitation model": they were referred to the NCTBLD
      by the index case; were queried about clinical symptoms suggestive of active TB
      disease; tuberculin skin testing and chest radiographs were performed.
      Demographic, laboratory, and clinical data of TB patients and their contacts were
      abstracted from existing records up to February 2013. RESULTS: 869 contacts of
      396 index cases were enrolled in the study; a median of 2 contacts were referred
      per index case. Among the 869 contacts, 47 (5.4%) were found to have or developed
      active TB disease: 30 (63.8%) were diagnosed with TB during the baseline period
      (co-prevalent cases) and 17 (36.2%) developed active TB disease during the follow
      up period (mean follow up of 21 months) (incident TB cases). The incidence rate
      of active TB disease among contacts was 1126.0 per 100,000 person years (95% CI
      655.7-1802.0 per 100,000 person-years). Among the 402 contacts who had a
      tuberculin skin test (TST) performed, 52.7% (95% CI 47.7-57.7%) had LTBI.
      CONCLUSIONS: A high prevalence of LTBI and active TB disease was found among the
      contacts of TB cases in Tbilisi, Georgia. Our findings demonstrated that an
      "invitation" model of contact investigation was an effective method of case
      detection. Therefore, contact investigation should be scaled up in Georgia.

PMID- 25379813
TI  - A real-time localization system for an endoscopic capsule using magnetic sensors.
AB  - Magnetic sensing technology offers an attractive alternative for in vivo tracking
      with much better performance than RF and ultrasound technologies. In this paper,
      an efficient in vivo magnetic tracking system is presented. The proposed system
      is intended to localize an endoscopic capsule which delivers biomarkers around
      specific locations of the gastrointestinal (GI) tract. For efficiently localizing
      a magnetic marker inside the capsule, a mathematical model has been developed for
      the magnetic field around a cylindrical magnet and used with a localization
      algorithm that provides minimum error and fast computation. The proposed tracking
      system has much reduced complexity compared to the ones reported in the
      literature to date. Laboratory tests and in vivo animal trials have demonstrated
      the suitability of the proposed system for tracking a magnetic marker with
      expected accuracy. 

PMID- 25379814
TI  - Temperature-independent fiber inclinometer based on orthogonally polarized modes
      coupling using a polarization-maintaining fiber bragg grating.
AB  - A reflection fiber inclinometer is proposed and experimentally demonstrated based
      on two linearly polarized (LP) modes coupling. The configuration consists of a
      section of polarization-maintaining fiber (PMF) containing a fiber Bragg grating
      (FBG) splicing with single mode fiber (SMF). Bending the PMF in the upstream of
      FBG can induce an additional birefringence of PMF, which results in the intensity
      changes of two LP modes owing to orthogonal polarization coupling. The
      experimental results represent that the device shows different bending responses
      at the angle range from 0 degrees  to 40 degrees and from 64 degrees  to 88
      degrees , respectively. Moreover, the temperature change just shifts the
      wavelengths of LP modes reflected and does not influence their intensities, which
      effectively avoid the temperature cross-sensitivity and make it a good candidate
      for measuring inclinometer and temperature simultaneously. 

PMID- 25379815
TI  - How good is the coverage and how accurate are exposure data in the Swedish
      Biologics Register (ARTIS)?
AB  - OBJECTIVES: To assess the coverage of the Swedish Biologics Register (Anti
      Rheumatic Therapy in Sweden, ARTIS) across indications, and the accuracy of the
      registered information on treatment with biologics. METHOD: Through cross
      reference of ARTIS to almost complete national health registers on prescriptions
      (adalimumab and etanercept), outpatient visits, and death/residency during 2008
      2010, we assessed: the treatment coverage of ARTIS for each treatment indication,
      the validity of the registered start and stop dates, ARTIS treatments with no
      corresponding drug dispensations, and the accuracy of the registered information
      on concomitant anti-rheumatic therapies. RESULTS: According to the national
      health registers, 3945 individuals with a spondyloarthropathy (SpA) and 8032
      patients with rheumatoid arthritis (RA) had filled at least one adalimumab or
      etanercept prescription during the study period. Of these, 86% of those with SpAs
      and 95% of patients with RA were also found in ARTIS with the corresponding
      treatment. Tumour necrosis factor (TNF) inhibitor prescriptions had been filled
      by 95% of patients between the ARTIS start and stop dates (allowing a 90-day
      window). More than 60 days before and more than 60 days after the registered
      start date in ARTIS, 5% and 4% respectively of patients had filled their first
      TNF inhibitor prescription. More than 90 days after the registered stop date in
      ARTIS, 8% of patients had filled one or more TNF inhibitor prescriptions.
      CONCLUSIONS: We observed a high coverage and accuracy of ARTIS data on biologics
      exposure, for both SpAs and RA. The combination of data from clinical registers
      such as ARTIS with data from national health registers offers a high quality
      measurement of actual treatment.

PMID- 25379816
TI  - The clinical, forensic and treatment outcome factors of patients with autism
      spectrum disorder treated in a forensic intellectual disability service.
AB  - BACKGROUND: To describe the characteristics of those with autism spectrum
      disorder (ASD) treated within a forensic intellectual disability hospital and to
      compare them with those without ASD. METHOD: Service evaluation of a cohort of
      138 patients treated over a 6-year period. RESULTS: Of the 138, 42 had an ASD.
      Personality disorders and harmful use or dependence on drugs were significantly
      lower in the ASD group. The ASD group was less likely to be subject to criminal
      sections or restriction orders. Self-harm was significantly higher in the ASD
      group. There were no differences in the length of stay and direction of care
      pathway. CONCLUSIONS: Although the ASD and non-ASD groups differ on clinical and
      forensic characteristics, their treatment outcomes appear similar. This suggests
      that the diagnostic category of ASD alone may be inadequate in predicting the
      treatment outcome. There is a case to identify distinct typologies within the ASD
      group.

PMID- 25379817
TI  - Clocks in algae.
AB  - As major contributors to global oxygen levels and producers of fatty acids,
      carotenoids, sterols, and phycocolloids, algae have significant ecological and
      commercial roles. Early algal models have contributed much to our understanding
      of circadian clocks at physiological and biochemical levels. The genetic and
      molecular approaches that identified clock components in other taxa have not been
      as widely applied to algae. We review results from seven species: the
      chlorophytes Chlamydomonas reinhardtii, Ostreococcus tauri, and Acetabularia
      spp.; the dinoflagellates Lingulodinium polyedrum and Symbiodinium spp.; the
      euglenozoa Euglena gracilis; and the red alga Cyanidioschyzon merolae. The
      relative simplicity, experimental tractability, and ecological and evolutionary
      diversity of algal systems may now make them particularly useful in integrating
      quantitative data from "omic" technologies (e.g., genomics, transcriptomics,
      metabolomics, and proteomics) with computational and mathematical methods. 

PMID- 25379818
TI  - Medial versus anterior open reduction for developmental hip dislocation in age
      matched patients.
AB  - BACKGROUND: The difference between medial (MAOR) and anterior (AAOR) approaches
      for open reduction of developmental hip dysplasia in terms of risk for avascular
      necrosis (AVN) and need for further corrective surgery (FCS, femoral and/or
      acetabular osteotomy) is unclear. This study compared age-matched cohorts
      undergoing either MAOR or AAOR in terms of these 2 primary outcomes. Prognostic
      impact of presence of ossific nucleus at time of open reduction was also
      investigated. METHODS: Institutional review board approval was obtained. Nineteen
      hips (14 patients) managed by MAOR were matched with 19 hips (18 patients)
      managed by AAOR based on age at operation (mean 6.0; range, 1.4 to 14.9 mo).
      Patients with neuromuscular conditions and known connective tissue disorders were
      excluded. Primary outcomes assessed at minimum 2 years' follow-up included
      radiographic evidence of AVN (Kalamchi and MacEwen) or requiring FCS. RESULTS:
      MAOR and AAOR cohorts were similar regarding age at open reduction, sex,
      laterality, and follow-up duration. One hip in each group had AVN before open
      reduction thus were excluded from AVN analysis. At minimum 2 years
      postoperatively (mean 6.2; range, 1.8 to 11.7 y), 4/18 (22%) MAOR and 5/18 (28%)
      AAOR met the same criteria for AVN (P=1.0). No predictors of AVN could be
      identified by regression analysis. Presence of an ossific nucleus preoperatively
      was not a protective factor from AVN (P=0.27). FCS was required in 4/19 (21%)
      MAOR and 7/19 (37%) AAOR hips (P=0.48). However, 7/12 (54%) hips failing closed
      reduction required FCS compared with 4/26 (16%) hips without prior failed closed
      reduction (P=0.024). Cox regression analysis showed that patients who failed
      closed reduction had an annual risk of requiring FCS approximately 6 times that
      of patients without a history of failed closed reduction (hazard ratio=6.1; 95%
      CI, 1.5-24.4; P=0.009), independent of surgical approach (P=0.55) or length of
      follow-up (P=0.78). CONCLUSIONS: In this study of age-matched patients undergoing
      either MAOR or AAOR, we found no association between surgical approach and risk
      of AVN or FCS. In addition, we identified no protective benefit of a preoperative
      ossific nucleus in terms of development of AVN. However, failing closed reduction
      was associated with a 6-fold increased annual risk of requiring FCS.
      SIGNIFICANCE: To the best of our knowledge, this is the first study comparing
      these 2 surgical techniques in an age-matched manner. It further corroborates
      previous studies stating that there may be no difference in risk of AVN based on
      surgical approach or presence of ossific nucleus preoperatively. LEVEL OF
      EVIDENCE: Level III-retrospective comparative study.

PMID- 25379819
TI  - A Modified Ogata-Goldsand Technique for Simplified Intraoperative Measurement of
      Femoral Version.
AB  - BACKGROUND: Femoral anteversion can be difficult to determine intraoperatively,
      particularly in cases with complicated deformity. Although biplanar methodology
      exists for measuring femoral anteversion, the measurements are generally based on
      the proximal femur, without consideration for the femoral bow. METHODS: We
      directly measured femoral version in 70 mature cadaveric femora. Using the
      standard Ogata-Goldsand approach, femoral version was geometrically calculated
      after measuring apparent neck-shaft angle and the beta-angle, which is the angle
      between the femoral neck and proximal femoral shaft on a direct lateral view. We
      then used a modified beta-angle, measured between the femoral neck and a line
      representing the entire femur. RESULTS: Mean anatomic femoral anteversion was
      20+/-11 degrees. Mean calculated femoral version using the standard Ogata
      Goldsand technique was 32+/-13 degrees, whereas mean calculated femoral version
      using the modified Ogata-Goldsand technique was 22+/-12 degrees. Repeated
      measures ANOVA analysis found an overall statistically significant difference
      between the 3 groups (P<0.0001). Pairwise comparisons revealed a significant
      difference between directly measured version and the standard Ogata-Goldsand
      technique (P<0.0001) but not between directly measured version and the modified
      Ogata-Goldsand technique (P=0.76). CONCLUSIONS: Standard biplanar imaging
      techniques do not account for the femoral bow and can significantly overestimate
      femoral anteversion. If a line is drawn from the posterior femoral condyles to
      the posterior aspect of the greater trochanter, femoral anteversion is better
      approximated. Intraoperatively, we obtain this line by positioning a marker over
      the skin under fluoroscopy. Clinically, if one aims for a modified beta-angle of
      5 degrees, a postosteotomy anteroposterior radiograph is no longer necessary,
      given the knowledge that with apparent neck-shaft angles ranging from 115 to 155
      degrees, version will lie within a generally accepted range between 2 and 11
      degrees. CLINICAL RELEVANCE: In complex operative cases where imaging is desired
      to measure intraoperative femoral version, we recommend a modified and simplified
      lateral view measurement technique, which improves accuracy by accounting for the
      femoral bow.

PMID- 25379820
TI  - Pediatric Humeral Osteomyelitis.
AB  - BACKGROUND: Osteomyelitis is a common problem among the pediatric population. The
      humerus is the most commonly affected bone in the upper limb; however, there are
      relatively few series in the literature. This article retrospectively reviews a
      large number of cases of pediatric humeral osteomyelitis. We aim to further
      define the disease and its clinical course to aid in improved treatment. METHODS:
      A 10-year retrospective review was performed of clinical records of pediatric
      humeral osteomyelitis at the 2 children's orthopaedic departments in the Auckland
      region. The Osteomyelitis Database was used to identify all cases between 1997
      and 2007 at Starship Children's Hospital, and 1998 and 2008 at Middlemore's Kidz
      First Hospital. RESULTS: Forty-nine patients were identified. Sixty-one percent
      were male with an average age of 4.2 years. Maori and Pacific Islanders were
      overrepresented. Seventy-eight percent were not using the limb, 70% complained of
      pain. Only 55% were febrile. White cell count, erythrocyte sedimentation rate,
      and C-reactive protein raised in 73%, 74%, and 79% of cases, respectively. X-ray,
      bone scintigraphy, and particularly magnetic resonance imaging were useful in
      radiologic diagnosis. Blood and tissue cultures revealed Staphylococcus aureus as
      the most common organism; there were 2 cases of community-acquired methicillin
      resistant S. aureus. The distal humerus was more commonly affected. Fifty-three
      percent required surgery. Antibiotic therapy averaged 2.7 weeks intravenous and
      2.6 weeks of oral therapy. There were 7 cases with adjacent septic arthritis,
      which had higher inflammatory markers. Major complications included 2 multiorgan
      failure and 1 growth disturbance. CONCLUSIONS: Humeral osteomyelitis can be
      diagnosed with an appropriate history, clinical examination, and investigations.
      One should be aware of concurrent septic arthritis and be prepared to treat this
      urgently. Those children with septic arthritis were not using the limb and had
      higher inflammatory markers. Treatment with intravenous and oral antibiotics and
      surgical debridement/washout if indicated can lead to good clinical outcomes with
      minimal complications. LEVEL OF EVIDENCE: Level IV-retrospective case series.

PMID- 25379821
TI  - Absence of Ligamentum Teres in Developmental Dysplasia of the Hip.
AB  - BACKGROUND: Ligamentum teres is hypertrophied and should be resected in
      developmental dysplasia of the hip (DDH). We have observed a relatively high
      prevalence of absence of ligamentum teres (ALT) in severe DDH. The purpose of
      this study was to determine: (1) the percentage of ALT in DDH; (2) the risk
      factors correlating with ALT; and (3) the pathologic characteristics of DDH with
      ALT. METHODS: In 2012, 123 patients were hospitalized for open reduction of DDH.
      Clinical records were retrospectively reviewed. The distribution of ALT was
      discerned. The risk factors correlating with ALT were analyzed. The pathologic
      changes of the DDH with ALT were observed. RESULTS: For the 123 patients, there
      were 14 males and 109 females with a mean age of 2.2+/-1.7 years old. Forty-one
      cases were diagnosed with bilateral DDH, and 27 of them had open reduction for
      both hips. Thus, 150 hips were included. According to the Tonnis grading, there
      were 1 grade I, 43 II, 67 III, and 39 IV patients. During operation, the
      ligamentum teres was confirmed absent in 24 patients (28 hips, 18.67%), 22 of the
      hips with ALT was Tonnis grade IV (78.57%). It was present in the other 99
      patients (122 hips). The difference of ALT among different grade (chi2=43.959,
      P=0.000) and different age (chi2=10.748, P=0.008) showed statistical
      significance, respectively. Logistic regression revealed only grading was the
      correlation factor of ALT (P=0.000). Pathologically, the femoral head was
      extremely small. The cartilage surface showed erosion-like change. The acetabulum
      was also diminutive but could match the femoral head well. CONCLUSIONS: At our
      institution, 18.67% of DDH needing open reduction was combined with ALT. The
      degree of dislocation was the only correlation factor of ALT. If the Tonnis grade
      was high, the hip was often associated with ALT. CLINICAL RELEVANCE: This study
      defines the prevalence of ALT and its risk factor in DDH, which will help to
      better understand the imaging, pathologic findings, and clinical outcome of DDH.

PMID- 25379822
TI  - Risk Factors for First Fractures Among Males With Duchenne or Becker Muscular
      Dystrophy.
AB  - BACKGROUND: Fractures are a significant concern for individuals with
      Duchenne/Becker muscular dystrophy with 21% to 44% of males experiencing a
      fracture. Factors that increase or decrease the risk for fracture have been
      suggested in past research, although statistical risk has not been determined.
      METHODS: In this retrospective cohort study, we used the Muscular Dystrophy
      Surveillance, Tracking and Research Network cohort, a large, population-based
      sample to identify risk factors associated with first fractures in patients with
      Duchenne or Becker muscular dystrophy. Our study cohort included males with
      Duchenne or Becker muscular dystrophy born between 1982 and 2006 who resided in
      Arizona, Colorado, Georgia, Iowa, and Western New York, retrospectively
      identified and followed through 2010. We utilized a multivariate Cox proportional
      hazard model to determine hazard ratios for relevant factors associated with
      first fracture risk including race/ethnicity, surveillance site, ambulation
      status, calcium/vitamin D use and duration, bisphosphonate use and duration, and
      corticosteroid use and duration. RESULTS: Of 747 cases, 249 had at least 1
      fracture (33.3%). Full-time wheelchair use increased the risk of first fracture
      by 75% for every 3 months of use (hazard ratio=1.75, 95% confidence interval,
      1.14, 2.68), but corticosteroid use, bisphosphonate use, and calcium/vitamin D
      use did not significantly affect risk in the final adjusted model. CONCLUSIONS:
      In this cohort, first fractures were common and full-time wheelchair use, but not
      corticosteroid use, was identified as a risk factor. The impact of prevention
      measures should be more thoroughly assessed. CLINICAL RELEVANCE: Fractures are a
      significant concern for individuals with dystrophinopathies, but the contribution
      of various risk factors has not been consistently demonstrated.

PMID- 25379823
TI  - Measurement Variability in the Evaluation of the Proximal Junction in Distraction
      based Growing Rods Patients.
AB  - BACKGROUND: Proximal junctional kyphosis (PJK) is a known complication of spinal
      fusion and has been shown to occur in the setting of growing rod instrumentation.
      Previous studies have shown good reliability in measuring PJK in adolescent
      idiopathic scoliosis. METHODS: Four pediatric orthopaedic spine surgeons measured
      the proximal junction in 10 patients with growing rod instrumentation using 2
      methods. In method 1, measurements were made from the inferior endplate of the
      upper instrumented vertebrae (UIV) to the superior endplate of 1 level above the
      UIV. In method 2, measurements were made from the inferior endplate 2 levels
      below the UIV to the superior endplate 2 levels above the UIV. These measurements
      were repeated 1 week later. RESULTS: Method 1 had an intraobserver variability of
      +/-13.2 degrees and interobserver variability of +/-21.6 degrees, whereas method
      2 had an intraobserver variability of +/-18.3 degrees and interobserver
      variability of +/-20.7 degrees. CONCLUSIONS: Interobserver variability of PJK is
      >20 degrees. As PJK is commonly defined as >10 degrees of kyphosis above the UIV,
      measurement of PJK in patients with distraction-based growing rods on lateral
      radiographs has too much variability to be useful. LEVEL OF EVIDENCE: Level III
      diagnostic studies.

PMID- 25379824
TI  - Surgical Treatment of Adolescent Acetabular Dysplasia With a Periacetabular
      Osteotomy: Does Obesity Increase the Risk of Complications?
AB  - BACKGROUND: The Bernese periacetabular osteotomy (PAO) is frequently used to
      treat symptomatic acetabular dysplasia in the adolescent age group. Despite
      encouraging results, factors predictive of the development of postoperative
      complications remain poorly understood. The purpose of this study was to
      investigate whether obesity is a risk factor for complications following PAO in
      adolescents. METHODS: A retrospective cohort study design was used to collect
      data from 3 different institutions. Children and adolescents (below 19 y of age)
      who underwent PAO and were followed for minimum of 12 months were included.
      Obesity was defined as a body mass index >=95 percentile. The modified Clavien
      Dindo classification was used to grade complications. A logistic regression
      analysis was used to identify factors related to the development of a
      complication that required treatment outside of routine postoperative care
      (complication grades II to V). Changes in radiographic parameters including
      Tonnis acetabular roof angle, anterior center-edge angle, and lateral center-edge
      angle among obese versus nonobese subjects were also evaluated. RESULTS: The mean
      age at surgery among the 84 adolescents included in the study was 16.5 years
      (range, 12 to 19 y). A total of 11% of the population was considered obese.
      Obesity (P=0.0047) was the only variable significantly associated with the
      development of a complication. After controlling for study site, the odds of an
      obese subject developing a complication were 10 [95% confidence interval (CI),
      1.89-59.8] times the odds of a nonobese subject developing a complication. There
      was no difference in the magnitude of change in anterior center-edge angle
      (P=0.1251), lateral center-edge angle (P=0.9774), or Tonnis (P=0.5770) angular
      correction that was achieved among the obese versus nonobese subjects following
      surgery. CONCLUSIONS: The Bernese PAO allows for adequate radiographic correction
      of acetabular dysplasia among obese and nonobese adolescents. However, the hip
      preservation surgeon should be aware of the higher risk of complications among
      obese adolescents undergoing PAO for the treatment of symptomatic acetabular
      dysplasia. LEVEL OF EVIDENCE: Level III-retrospective study.

PMID- 25379825
TI  - Long-term Functional Results of Neurological Complications of Pediatric Humeral
      Supracondylar Fractures.
AB  - PURPOSE: It has been reported that most neurological injuries after sustaining a
      supracondylar fracture will usually resolve spontaneously in the first months;
      however, studies are lacking regarding the influence of these injuries in the
      upper limb functionality in the long-term follow-up. The aim of this study is to
      report the long-term functional outcome of neurological complications associated
      to pediatric supracondylar fractures. METHODS: Medical records of 448 children
      who sustained a supracondylar humeral fracture were reviewed. Patients with a
      concomitant neurological injury were included. Clinical evaluation included grip
      and pinch strength and a thorough examination of sensibility. Clinical outcomes
      were described according to the Mayo Elbow Performance Score and Flynn criteria.
      Patients completed the quick Disabilities of the Arm, Shoulder and Hand
      questionnaire (QuickDASH) questionnaire. RESULTS: There were 29 patients with a
      supracondylar humeral fracture and a neurological injury (6.5%). The median nerve
      was injured in 13 patients, the radial nerve in 14 patients and the ulnar nerve
      in 9 patients. Of them, 16 patients returned for clinical evaluation. The mean
      age at the time of fracture was 7.5+/-1.9 years and at revision 16+/-5.3 years.
      The average follow-up was 8.6+/-4.8 years (3.4 to 17.4 y). There were no
      differences in terms of grip or pinch strength. Seven patients referred
      paresthesias, 6 of them in the ulnar nerve's territory. The average score was 4+/
      3 (median, 4) for the QuickDASH questionnaire and 96+/-7 for the Mayo Elbow
      Performance Score. According to Flynn criteria, results were satisfactory in 10
      cases. DISCUSSION: Functional results were excellent in the majority of patients.
      Almost half of the patients referred paresthesias, mostly in the ulnar nerve
      territory, that were not limiting normal daily activity. At final follow-up,
      although 100% of the radial nerve injuries and 87.5% of the median nerve injuries
      were fully recovered, only 25% of the ulnar nerve injuries were. LEVEL OF
      EVIDENCE: Level IV-prognostic study.

PMID- 25379826
TI  - Subaxial cervical spine injuries in children and adolescents.
AB  - BACKGROUND: Limited data exist on pediatric subaxial cervical spine injuries. The
      goal of this study was to characterize the injuries and initial treatment of a
      large consecutive series of patients with injuries from C3 to C7. METHODS:
      Medical records and radiographs of consecutive patients admitted with cervical
      spine fractures and/or dislocations at a single level 1 pediatric trauma center
      from 2003 to 2013 were reviewed. Data abstracted included age, injury type and
      level, mechanism of injury, associated nonspine injuries, neurological status,
      length of hospitalization, and initial treatment. RESULTS: Fifty-one patients
      were grouped into 3 age ranges: infant, 0 to 3 years (2); youth, 4 to 12 years
      (13); and adolescent, 13 to 16 years (36). Isolated fractures were identified in
      both infants and accounted for most of injuries in youths (85%) and adolescents
      (86%). Single vertebra or single vertebral level injuries were present in 65% of
      patients, most commonly at C7 (36%) or C6 (29%). No correlation existed between
      cervical level injured and patient age. Multiple cervical spine injuries occurred
      in 1 infant, 3 youths, and 14 adolescents. Other concomitant thoracic and/or
      lumbar spine injuries were found in 1 infant and 3 adolescents. The most common
      mechanisms of injury were motor vehicle accidents (53%) and sports (14%). High
      energy trauma was associated with higher rates of noncontiguous spinal injuries
      and associated nonspinal injuries, with a longer length of hospitalization.
      Neurological deficits were observed in 8 patients: 1 infant, 2 youths, and 5
      adolescents, of which 5 resulted from high-energy trauma. One infant and all
      youth patients were treated nonoperatively; 26 adolescents (73%) were treated in
      a cervical collar or with observation, 1 was treated with halo-vest
      immobilization, and 9 had surgical treatment. CONCLUSIONS: Most subaxial cervical
      spine injuries in pediatric and adolescent patients are isolated fractures at C6
      and C7. High-energy mechanisms are associated with noncontiguous spinal injuries
      and other nonspine injuries. Most patients can be treated in a cervical collar,
      but adolescent patients are more likely to require halo placement or surgical
      intervention. LEVEL OF EVIDENCE: Level IV-retrospective, diagnostic.

PMID- 25379827
TI  - Pelvic Incidence and Acetabular Version in Slipped Capital Femoral Epiphysis.
AB  - BACKGROUND: The etiology of slipped capital femoral epiphysis (SCFE) is
      multifactorial, but the role of sagittal balance of the pelvis as a contributing
      factor to its development has not been well studied. Our primary purpose was to
      determine whether a smaller pelvic incidence (PI), a position-independent
      anatomic parameter that regulates pelvic orientation, could be a factor that
      increases shear stress in the epiphyseal growth plate and potentially contributes
      to the development of SCFE. We also set out to determine whether acetabular
      retroversion was associated with SCFE. METHODS: We obtained 14 cadaveric pelvi
      from the Hamann-Todd Osteological Collection whose femurs showed evidence of post
      SCFE deformity. Two hundred age-matched, sex-matched, and race-matched pelvi were
      used as controls. PI and acetabular version were measured using standardized
      lateral photographs and goniometers, respectively. T tests were performed to
      evaluate for differences in measured parameters between groups. RESULTS: The mean
      PI was 40.6+/-6.1 degrees for SCFE specimens and 47.4+/-9.9 degrees for normal
      specimens (P=0.01). The mean version of SCFE and normal acetabula was 15+/-7 and
      17+/-6 degrees, respectively (P=0.39). There was also no significant difference
      in version between SCFE acetabula and the contralateral, uninvolved acetabular of
      the same specimen (15+/-7 vs. 17+/-8 degrees, P=0.33). CONCLUSIONS: Specimens
      with SCFE deformity demonstrated a smaller PI than a large cohort of normal
      control specimens. We found no significant difference between acetabular version
      of specimens with and without SCFE deformity. Contralateral or unaffected
      acetabuli of SCFE specimens were not more retroverted than the affected side of
      the same specimen. CLINICAL RELEVANCE: Sagittal balance of the pelvis, and
      particularly decreased PI, may play an important role in the development of SCFE.
      The influence of mechanical factors beyond the hip joint in the development of
      SCFE should be considered by clinicians.

PMID- 25379828
TI  - Outcome of Displaced Fractures of the Distal Metaphyseal-Diaphyseal Junction of
      the Humerus in Children Treated With Elastic Stable Intramedullary Nails.
AB  - BACKGROUND: The main objective of this study was to retrospectively evaluate the
      clinical and radiographic outcomes of displaced distal humeral metaphyseal
      diaphyseal junction fractures in children treated by elastic stable
      intramedullary nailing (ESIN). METHODS: During the study period, 14 consecutive
      children with fractures of the distal humeral metaphyseal-diaphyseal junction
      were surgically treated by ESIN. All patients underwent full-length preoperative
      and postoperative anteroposterior and lateral radiographs of the injured humerus.
      One year after the index surgery, patients were asked to answer the short version
      of the Disabilities of the Arm, Shoulder and Hand outcome questionnaire (Quick
      DASH). RESULTS: During the study period, fractures of the distal metaphyseal
      diaphyseal humeral junction represented 1.5% (16/1100) of all humeral fractures.
      Fourteen patients underwent surgery and met the inclusion criteria. The male to
      female ratio was 1:1. The average patient age at the time of injury was 9.7 years
      (range, 3.6 to 13.7 y). The left and right sides were equally affected. The mean
      follow-up was 28.1 months (range, 20 to 38 mo).Radiologically, no secondary
      displacement, nail migration, loss of fixation, consolidation delay, nonunion, or
      refracture was noted. None of the patients showed signs of growth arrest on
      either radiologic or clinical assessment.All patients returned to their previous
      daily and sport activities without discomfort or difficulty, and they were free
      of pain at their last follow-up visits. The injured elbow range of motion was
      comparable with that of the contralateral side at the last follow-up visit in all
      patients. The mean Quick DASH score was 0.81 (range, 0 to 6.8). CONCLUSIONS: We
      recommend surgery for displaced fractures of the distal humeral metaphyseal
      diaphyseal junction. ESIN results in stable reduction, good rotational control,
      and faster mobilization. LEVEL OF EVIDENCE: Level IV.

PMID- 25379829
TI  - Acetabular Protrusio and Proximal Femur Fractures in Patients With Osteogenesis
      Imperfecta.
AB  - BACKGROUND: Osteogenesis imperfect (OI) is a genetic disorder characterized by
      increased bone fragility, frequent fractures, and extremity deformities among
      other clinical findings. A frequent radiographic finding in OI patients is
      acetabular protrusio (AP). We hypothesized that AP incidence would be significant
      in OI patients and highest among type III OI patients, who have a more severe
      disease phenotype. In addition, we hypothesized that there would be a correlation
      between AP and proximal femur fracture incidence. METHODS: We retrospectively
      reviewed radiographs and medical records of 49 patients with OI evaluated at our
      institution. Demographic information and modified Sillence classification were
      recorded. AP was diagnosed using previously published radiographic criteria using
      the center-edge angle of Wiberg, acetabulum relative to the iliopectineal line,
      teardrop figure relative to the ilioischial (Kohler) line, and acetabulum
      relative to the ilioischial (Kohler) line. Medical record and radiographs were
      reviewed for evidence of proximal femur or acetabulum fracture. Associations
      between OI type, AP, and fracture incidence were examined with chi or Fisher
      exact tests. RESULTS: In this series of 49 OI patients, the overall incidence of
      AP was 55.1% (27/49) with the highest incidence among patients with type III OI
      (70.6%). There was an increased incidence of proximal femur, and particularly
      femoral neck, fractures among patients with AP compared with patients with normal
      hip anatomy. Overall, patients with AP had a 30% increased risk for proximal
      femur and acetabulum fractures (P=0.03). CONCLUSIONS: AP is a common deformity in
      OI patients (55.1%) and particularly type III OI (70.6%). Patients with AP have
      an increased risk for proximal femur fractures and particularly femoral neck
      fractures. This novel finding adds to the growing body of literature on clinical
      implications of AP in OI patients. LEVEL OF EVIDENCE: Level IV-Retrospective case
      series.

PMID- 25379830
TI  - The Outcome of Surgical Treatment of Multidirectionally Unstable (Type IV)
      Pediatric Supracondylar Humerus Fractures.
AB  - BACKGROUND: The outcome of multidirectionally unstable (type IV) supracondylar
      humerus fractures (SCHF) has been rarely described. We aimed to describe several
      aspects related to the diagnosis, treatment, and outcome of this complex injury.
      METHODS: We analyzed the clinical and radiographic data on 130 completely
      displaced SCHF in children, which was collected prospectively over a 6-year
      period (2007 to 2013), as part of an IRB-approved study. A minimum follow-up of 6
      weeks was required. We compared the outcome of type IV SCHF (n=12, group 1) with
      that of type III SCHF (n=118, group 2) by assessing the need for open reduction,
      length of operative time, recovery of range of motion (as compared with the
      normal, contralateral side), and rate of complications. RESULTS: An open
      reduction was required in 17% and 2% of fractures in groups 1 and 2, respectively
      (P=0.04). A medial pin was added to supplement the fixation in 42% and 17% of
      fractures in groups 1 and 2, respectively (P=0.05). An acceptable reduction was
      obtained in all fractures. Surgery was longer for fractures in group 1, by a mean
      of 22 minutes (P=0.0001). No patient in either group required a reoperation.
      There was no significant difference between groups with respect to the latest
      range of motion of the treated side, as compared with the normal contralateral
      side (98% vs. 97%, respectively, P=0.4). Satisfactory outcomes were found in 92%
      and 98% of patients in groups 1 and 2, respectively (P=0.6). CONCLUSIONS: The
      results of this study suggest that a satisfactory outcome can be expected when
      treating type IV SCHF in a child. Although these fractures are associated with
      increased levels of technical difficulty, given the increased need for open
      reduction, utilization of medial pins, and longer surgical times, adequate
      reductions and satisfactory mid-term to long-term outcomes can be achieved. LEVEL
      OF EVIDENCE: Level II.

PMID- 25379831
TI  - Response to letter to the editor re: immediate intramedullary flexible nailing of
      open pediatric tibial shaft fractures.

PMID- 25379832
TI  - Implications and impact of prior authorization policy on vancomycin use at a
      tertiary pediatric teaching hospital.
AB  - BACKGROUND: We evaluated the performance of two consecutive antimicrobial
      stewardship interventions on vancomycin use. METHODS: Prospective audit with
      intervention and real time feedback to providers were implemented in April 2004.
      In February 2009, the institutional vancomycin policy was modified requiring
      preauthorization by the pediatric infectious diseases clinician on-call. Monthly
      vancomycin use was calculated as doses administered per 1000 patient-days.
      RESULTS: After 5 years of prospective-audit vancomycin use declined from 378
      doses administered/1000 patient-days to 208 doses administered/1000 patient-days
      (45%). Following the implementation of preauthorization, vancomycin use decreased
      by an additional 16% in the subsequent 4 years. When compared with the trend of
      vancomycin use with prospective-audit, the trend of vancomycin use after the
      implementation of the restriction policy increased by 3.9 doses per month (SE:
      1.51, P=0.012) during the subsequent 51 months. CONCLUSIONS: Implementation of
      preauthorization didn't significantly reduce the use of vancomycin beyond the
      accomplishments by prospective-audit and feedback by a team of an infectious
      disease pharmacist and physician.

PMID- 25379833
TI  - Etiology and epidemiology of children with acute otitis media and spontaneous
      otorrhea in Suzhou, China.
AB  - BACKGROUND: There are scare data about bacterial etiology and the antibiotic
      susceptibility, serotype distribution and molecular characteristics of
      pneumococci in children with acute otitis media (AOM) in China. METHODS: A
      prospective study was conducted in Suzhou University Affiliated Children's
      Hospital. All children under 18 years of age diagnosed as AOM and with
      spontaneous otorrhea were offered enrollment, and collection of middle ear fluid
      was then cultured for bacterial pathogens. The antibiotic susceptibility,
      serotypes, macrolide resistance genes and sequence types of Streptococcus
      pneumoniae strains were identified. RESULTS: From January 2011 to December 2013,
      a total of 229 cases of AOM with spontaneous otorrhea were identified; of these,
      159 (69.4%) middle ear fluid specimens were tested positive for bacterial
      pathogens. The leading cause was S. pneumoniae (47.2%), followed by
      Staphylococcus aureus (18.8%) and Haemophilus influenzae (7.4%). The antibiotic
      resistance rates of S. pneumoniae isolates to erythromycin were 99.1%, and the
      nonsusceptible rate to penicillin was 54.6%. The most common serotypes identified
      were 19A (45.1%) and 19F (35.4%). The coverage against PCV7 serotypes for this
      outcome was 56.1% and of PCV13 was 97.6%. The macrolide resistance was mainly
      mediated by both ermB and mefA/E genes (88.6%). The CC271 was the major clonal
      complex identified. CONCLUSIONS: S. pneumoniae was a leading cause for AOM in
      children in Suzhou, China. Antibiotics resistance rates of S. pneumoniae were
      high and mainly due to the spread of CC271 clonal complex.

PMID- 25379834
TI  - Seasonal variation in penicillin susceptibility and invasive pneumococcal
      disease.
AB  - We evaluated prospectively laboratory surveillance data from Massachusetts to
      investigate whether seasonal variation in invasive pneumococcal disease is
      associated with the proportion of penicillin-susceptible isolates. The proportion
      of penicillin-susceptible isolates associated with invasive pneumococcal disease
      varied by season, with proportions highest in the winter and lowest in the
      summer, and rates of invasive disease were highest in the autumn and winter
      seasons and lowest in the summer. 

PMID- 25379835
TI  - Interpreting a post-partum Kleihauer test.

PMID- 25379836
TI  - Decreased whole blood RNA expression of cathelicidin in HIV-infected heroin users
      in Bandung, Indonesia.
AB  - The antimicrobial peptide cathelicidin is critical in killing pathogens by innate
      immune cells, including Mycobacterium tuberculosis and Candida albicans. These
      pathogens often cause infections in opioid users, a risk that is greatly
      increased with concurrent human immunodeficiency virus (HIV) infection.
      Therefore, we examined the association between opioid use and cathelicidin in HIV
      infected subjects from Bandung, Indonesia. The following three groups of HIV
      infected individuals were included: (i) Active drug users: used heroin in the
      last 30 days; (ii) Methadone clients: received methadone maintenance therapy in
      the last 30 days; and (iii) CONTROLS: never used opioids or did not use opioids
      in the year preceding inclusion. In addition to interviews, blood samples were
      taken to examine the RNA expression of cathelicidin. We found that the RNA
      expression of cathelicidin was significantly decreased (p=0.007) in heroin users,
      compared with controls. Opioids are associated with immunosuppression, and
      cathelicidin could be an important factor in this association. However, more
      research is needed to examine the direct effects of decreased cathelicidin
      levels.

PMID- 25379837
TI  - Artificial metalloenzymes for the diastereoselective reduction of NAD(+) to
      NAD(2)H.
AB  - Stereoselectively labelled isotopomers of NAD(P)H are highly relevant for
      mechanistic studies of enzymes which utilize them as redox equivalents. Whereas
      several methods are firmly established for their generation in high
      diastereomeric purity by enzymatic methods, alternative methods have so far not
      been investigated. The article presents the stereoselective deuteration of NAD(+)
      at the 4-position (90% de) of the pyridinium-ring by means of an artificial
      metalloenzyme. The artificial metalloenzyme consists of a biotinylated iridium
      cofactor embedded in streptavidin isoforms and the resulting constructs have been
      previously shown to be compatible with natural enzymes. Alternative methods for
      stereoselective NAD(P)(+) reduction are expected to be of high interest for the
      mechanistic study of enzymes that accept NAD(P)H mimics and for the synthesis of
      structurally related fine chemicals. 

PMID- 25379838
TI  - Choice of rating scale labels: implication for minimizing patient satisfaction
      response ceiling effect in telemedicine surveys.
AB  - BACKGROUND: Lack of response variability is problematic in surveys because of its
      detrimental effects on sensitivity and consequently reliability of the responses.
      In satisfaction surveys, this problem is caused by the ceiling effect resulting
      from high satisfaction ratings. A potential solution strategy is to manipulate
      the labels of the rating scale to create greater discrimination of responses on
      the high end of the response continuum. This study examined the effects of a
      positive-centered scale on the distribution and reliability of telemedicine
      satisfaction responses in a highly positive respondent population. MATERIALS AND
      METHODS: In total, 216 telemedicine participants were randomly assigned to one of
      three experimental conditions as defined by the form of Likert scale: (1) 5-point
      Balanced Equal-Interval, (2) 5-point Positive-Packed, and (3) 5-point Positive
      Centered Equal-Interval. RESULTS: Although the study findings were not
      statistically significant, partially because of sample size, the distribution and
      internal consistency reliability of responses occurred in the direction
      hypothesized. Loading the rating scale with more positive labels appears to be a
      useful strategy for reducing the ceiling effect and increases the discrimination
      ability of survey responses. CONCLUSIONS: The current research provides a survey
      design strategy to minimize ceiling effects. Although the findings provide some
      evidence suggesting the benefit of using rating scales loaded with positive
      labels, more research is needed to confirm this, as well as extend it to examine
      other types of rating scales and the interaction between rating scale formats and
      respondent characteristics.

PMID- 25379839
TI  - Controlling the characteristics of lamellar liquid crystals using counterion
      choice, fluorination and temperature.
AB  - The characteristics of robust and highly ordered fluorinated lamellar phases were
      explored as a function of temperature, counterion identity and fluorination of
      the surfactant and co-surfactant. Structural and composition effects were probed
      using a combination of small-angle scattering of X-rays and neutrons, polarising
      microscopy and calorimetry. It was found that in general, the phases remained
      remarkably stable with increasing temperature, showing only moderate loss of
      order and increased membrane flexibility. By changing the surfactant's cationic
      counterion, it was possible to exert influence on both the shape of micelles
      formed and the inter-layer spacing of the lamellar phases obtained. Ordering and
      crystallinity of the lamellar membranes could be controlled by the level of
      fluorination of both the surfactant and co-surfactant. These results suggest that
      subtle manipulations of selected control parameters including co-surfactant
      selection and counterion choice can provide a high level of control over membrane
      spacing and local order within lamellar phases, providing guidance where these
      materials are used as templates. 

PMID- 25379840
TI  - Anaesthetic techniques for risk of malignant tumour recurrence.
AB  - BACKGROUND: Surgery remains a mainstay of treatment for malignant tumours;
      however, surgical manipulation leads to a significant systemic release of tumour
      cells. Whether these cells lead to metastases is largely dependent on the balance
      between aggressiveness of the tumour cells and resilience of the body. Surgical
      stress per se, anaesthetic agents and administration of opioid analgesics
      perioperatively can compromise immune function and might shift the balance
      towards progression of minimal residual disease. Regional anaesthesia techniques
      provide perioperative pain relief; they therefore reduce the quantity of systemic
      opioids and of anaesthetic agents used. Additionally, regional anaesthesia
      techniques are known to prevent or attenuate the surgical stress response. In
      recent years, the potential benefit of regional anaesthesia techniques for tumour
      recurrence has received major attention and has been discussed many times in the
      literature. In preparing this review, we aimed to summarize the current evidence
      systematically and comprehensively. OBJECTIVES: To establish whether anaesthetic
      technique (general anaesthesia versus regional anaesthesia or a combination of
      the two techniques) influences the long-term prognosis for individuals with
      malignant tumours. SEARCH METHODS: We searched The Cochrane Library (2013, Issue
      12), PubMed (1950 to 15 December 2013), EMBASE (1974 to 15 December 2013), BIOSIS
      (1926 to 15 December 2013) and Web of Science (1965 to 15 December 2013). We
      handsearched relevant websites and conference proceedings and reference lists of
      cited articles. We applied no language restrictions. SELECTION CRITERIA: We
      included all randomized controlled trials or controlled clinical trials that
      investigated the effects of general versus regional anaesthesia on the risk of
      malignant tumour recurrence in patients undergoing resection of primary malignant
      tumours. Comparisons of interventions consisted of (1) general anaesthesia alone
      versus general anaesthesia combined with one or more regional anaesthetic
      techniques; (2) general anaesthesia combined with one or more regional
      anaesthetic techniques versus one or more regional anaesthetic techniques; and
      (3) general anaesthesia alone versus one or more regional anaesthetic techniques.
      Primary outcomes included (1) overall survival, (2) progression-free survival and
      (3) time to tumour progression. DATA COLLECTION AND ANALYSIS: Two review authors
      independently scanned the titles and abstracts of identified reports and
      extracted study data.All primary outcome variables are time-to-event data. If the
      individual trial report provided summary statistics with odds ratios, relative
      risks or Kaplan-Meier curves, extracted data enabled us to calculate the hazard
      ratio using the hazard ratio calculating spreadsheet. To assess risk of bias, we
      used the standard methodological procedures expected by The Cochrane
      Collaboration. MAIN RESULTS: We included four studies with a total of 746
      participants. All studies included adult patients undergoing surgery for primary
      tumour resection. Two studies enrolled male and female participants undergoing
      major abdominal surgery for cancer. One study enrolled male participants
      undergoing surgery for prostate cancer, and one study male participants
      undergoing surgery for colon cancer. Follow-up time ranged from nine to 17 years.
      All four studies compared general anaesthesia alone versus general anaesthesia
      combined with epidural anaesthesia and analgesia. All four studies are secondary
      data analyses of previously conducted prospective randomized controlled trials.Of
      the four included studies, only three contributed to the outcome of overall
      survival, and two each to the outcomes of progression-free survival and time to
      tumour progression. In our meta-analysis, we could not find an advantage for
      either study group for the outcomes of overall survival (hazard ratio (HR) 1.03,
      95% confidence interval (CI) 0.86 to 1.24) and progression-free survival (HR
      0.88, 95% CI 0.56 to 1.38). For progression-free survival, the level of
      inconsistency was high. Pooled data for time to tumour progression showed a
      slightly favourable outcome for the control group (general anaesthesia alone)
      compared with the intervention group (epidural and general anaesthesia) (HR 1.50,
      95% CI 1.00 to 2.25).Quality of evidence was graded low for overall survival and
      very low for progression-free survival and time to tumour progression. The
      outcome of overall survival was downgraded for serious imprecision and serious
      indirectness. The outcomes of progression-free survival and time to tumour
      progression were also downgraded for serious inconsistency and serious risk of
      bias, respectively.Reporting of adverse events was sparse, and data could not be
      analysed. AUTHORS' CONCLUSIONS: Currently, evidence for the benefit of regional
      anaesthesia techniques on tumour recurrence is inadequate. An encouraging number
      of prospective randomized controlled trials are ongoing, and it is hoped that
      their results, when reported, will add evidence for this topic in the near
      future.

PMID- 25379841
TI  - Core-shell nanoparticles and enhanced polarization in polymer based nanocomposite
      dielectrics.
AB  - We present a detailed study of the evolution and nature of metallic core-oxide
      shell particles and the role of nanostructure in the physics of enhanced
      polarization in polymer-nanocomposite (PNC) based dielectrics. Nylon-6 based PNCs
      consisting of aluminium (core)-aluminium oxide (shell) nanoparticles were
      fabricated by a vacuum deposition technique. Their resulting high polarizability
      was closely related to the formation and chemistry of the core-shell structure
      that was revealed by transmission electron microscopy to comprise a highly
      defective, strained and non-stoichiometric semi-crystalline/amorphous Al-oxide
      shell. 

PMID- 25379842
TI  - The pleasure of surgery: my pleasure in being a surgeon.

PMID- 25379843
TI  - Being a surgeon--the myth and the reality: a meta-synthesis of surgeons'
      perspectives about factors affecting their practice and well-being.
AB  - OBJECTIVES: Synthesize the findings from individual qualitative studies about
      surgeons' account of their practice. BACKGROUND: Social and contextual factors of
      practice influence doctors' well-being and therapeutic relationships. Little is
      known about surgery, but it is generally assumed that surgeons are not affected
      by them. METHODS: We searched international publications (2000-2012) to identify
      relevant qualitative research exploring how surgeons talk about their practice.
      Meta-ethnography (a systematic analysis of qualitative literature that
      compensates for the potential lack of generalizability of the primary studies and
      provides new insight by their conjoint interpretation) was used to identify key
      themes and synthesize them. RESULTS: We identified 51 articles (>1000 surgeons)
      from different specialties and countries. Two main themes emerged. (i) The
      patient-surgeon relationship, described surgeons' characterizations of their
      relationships with patients. We identified factors influencing surgical decision
      making, communication, and personal involvement in the process of care; these
      were surgeon-related, patient-related, and contextual. (ii) Group relations and
      culture described perceived issues related to surgical culture (image and
      education, teamwork, rules, and guidelines); it highlighted the influence of a
      social dimension on surgical practice. In both themes, we uncovered an emotional
      dimension of surgeons' practice. CONCLUSIONS: Surgeons' emphasis on technical
      aspects, individuality, and performance seems to impede a modern patient-centered
      approach to care and to act as a barrier to well-being. Our findings suggest that
      taking into account the relational and emotional dimensions of surgical practice
      (both with patients and within the institution) might improve surgical
      innovation, surgeons' well-being, and the attractiveness of this specialty.

PMID- 25379844
TI  - Multicenter double-blinded randomized controlled trial of standard abdominal
      wound edge protection with surgical dressings versus coverage with a sterile
      circular polyethylene drape for prevention of surgical site infections: a CHIR
      Net trial (BaFO; NCT01181206).
AB  - OBJECTIVE: To determine whether circular plastic wound edge protectors (CWEPs)
      significantly reduce the rate of surgical site infections (SSIs) in comparison to
      standard surgical towels in patients undergoing laparotomy. BACKGROUND: SSIs
      cause substantial morbidity, prolonged hospitalization, and costs and remain one
      of the most frequent surgical complications. CWEPs have been proposed as a
      measure to reduce the incidence of SSIs. METHODS: In this randomized controlled,
      multicenter, 2-arm, parallel-group design, patient- and observer-blinded trial
      patients undergoing open elective abdominal surgery were assigned to either
      intraoperative wound coverage with a CWEP or standard coverage with surgical
      towels. Primary endpoint was superiority of intervention over control in terms of
      the incidence of SSIs within a 30-day postoperative period. RESULTS: Between
      September 2010 and November 2012, 608 patients undergoing laparotomy were
      randomized at 16 centers across Germany. Three patients in the device group and
      11 patients in the control group did not undergo laparotomy. Patients' and
      procedural characteristics were well balanced between the 2 groups. Forty-eight
      patients discontinued the study prematurely, mainly because of relaparotomy
      (control, n=9; intervention, n=9) and death (control, n=4; intervention, n=7). A
      total of 79 patients experienced SSIs within 30 days of surgery, 27 of 274 (9.9%)
      in the device group and 52 of 272 (19.1%) in the control group (odds ratio=0.462,
      95% confidence interval: 0.281-0.762; P=0.002). Subgroup analyses indicate that
      the effect could be more pronounced in colorectal surgery, and in clean
      contaminated/contaminated surgeries. CONCLUSIONS: Our trial shows that CWEPs are
      effective at reducing the incidence of SSIs in elective and clean or clean
      contaminated open abdominal surgery.

PMID- 25379845
TI  - Effectiveness of regional hyperthermia with chemotherapy for high-risk
      retroperitoneal and abdominal soft-tissue sarcoma after complete surgical
      resection: a subgroup analysis of a randomized phase-III multicenter study.
AB  - OBJECTIVE: To determine whether regional hyperthermia (RHT) in addition to
      chemotherapy improves local tumor control after macroscopically complete
      resection of abdominal or retroperitoneal high-risk sarcomas. BACKGROUND: Within
      the prospectively randomized EORTC 62961 phase-III trial, RHT and systemic
      chemotherapy significantly improved local progression-free survival (LPFS) and
      disease-free survival (DFS) in patients with abdominal and extremity sarcomas.
      That trial included macroscopically complete and R2 resections. METHODS: A
      subgroup analysis of the EORTC trial was performed and long-term survival
      determined. From 341 patients, 149 (median age 52 years, 18-69) were identified
      with macroscopic complete resection (R0, R1) of abdominal and retroperitoneal
      soft-tissue sarcomas (median diameter 10 cm, G2 48.3%, G3 51.7%). Seventy-six
      patients were treated with EIA (etoposide, ifosfamide, doxorubicin)+RHT (>=5
      cycles: 69.7%) versus 73 patients receiving EIA alone (>=5 cycles: 52.1%,
      P=0.027). LPFS and DFS as well as overall survival were determined. RESULTS: RHT
      and systemic chemotherapy significantly improved LPFS (56% vs 45% after 5 years,
      P=0.044) and DFS (34% vs 27% after 5 years, P=0.040). Overall survival was not
      significantly improved in the RHT group (57% vs 55% after 5 years, P=0.82).
      Perioperative morbidity and mortality were not significantly different between
      groups. CONCLUSIONS: In patients with macroscopically complete tumor resection,
      RHT in addition to chemotherapy resulted in significantly improved local tumor
      control and DFS without increasing surgical complications. Within a multimodal
      therapeutic concept for abdominal and retroperitoneal high-risk sarcomas, RHT is
      a treatment option beside radical surgery and should be further evaluated in
      future trials.

PMID- 25379846
TI  - The comprehensive complication index: a novel and more sensitive endpoint for
      assessing outcome and reducing sample size in randomized controlled trials.
AB  - OBJECTIVE: To test whether the newly developed comprehensive complication index
      (CCI) is more sensitive than traditional endpoints for detecting between-group
      differences in randomized controlled trials (RCTs). BACKGROUND: A major challenge
      in RCTs is the choice of optimal endpoints to detect treatment effects. Mortality
      is no longer a sufficient marker in studies, and morbidity is often poorly
      defined. The CCI, integrating all complications including their severity in a
      linear scale ranging from 0 (no complication) to 100 (death), is a new tool,
      which may be more sensitive than other traditional endpoints to detect treatment
      effects on postoperative morbidity. METHODS: The CCI was tested in 3 published
      RCTs from European centers evaluating pancreas, esophageal and colon resections.
      To compare the sensitivity of the CCI with traditional morbidity endpoints, for
      example, presence of any (yes/no) or only the most severe complications, all
      postoperative events were assessed, and the CCI calculated. Treatment effects and
      sample size calculations were compared using the CCI and traditional endpoints.
      RESULTS: Although RCTs failed to show between-group differences using any or most
      severe complications, the CCI revealed significant differences between treatment
      groups in 2 RCTs-after pancreas (P=0.009) and esophageal surgery (P=0.014). The
      CCI in the RCT on colon resections confirmed the absence of between-group
      differences (P=0.39). The required sample sizes in trials are up to 9 times lower
      for the CCI than for traditional morbidity endpoints. CONCLUSIONS: This study
      demonstrates superiority of the CCI to traditional endpoints. The CCI may serve
      as an appealing endpoint for future RCTs and may reduce the sample size.

PMID- 25379848
TI  - New-onset atrial fibrillation post-surgery for esophageal and junctional cancer:
      incidence, management, and impact on short- and long-term outcomes.
AB  - OBJECTIVE: To study new-onset postoperative atrial fibrillation in patients with
      esophageal and junctional cancer. DESIGN: Retrospective cohort study from a
      prospective data base. BACKGROUND: Atrial fibrillation (AF) is common after
      thoracic and esophageal surgical procedures. The full spectrum of risk factors,
      associations, and implications are unclear. METHODS: All patients undergoing
      multimodal therapy or surgery with curative intent from 2006 to mid-2013 were
      studied. New-onset AF was recorded prospectively. Risk factors, management and
      resolution, association with other complications, and impact on in-hospital
      mortality and longer-term oncologic outcomes were analyzed in retrospective
      cohort analysis. RESULTS: A total of 473 patients (mean age: 63 years; 73% male)
      underwent resection, 51% 2-stage, 18% 3-stage, 12% transhiatal, and 19% extended
      total gastrectomy. Ninety-six (20%) patients developed new-onset AF, in 18%, 27%,
      29%, and 14% of 2-, 3-, transhiatal, and extended total gastrectomy cohorts,
      respectively (P=0.05). Age, diabetes, neoadjuvant therapy, and cardiac history
      predisposed (P<0.05) to AF, and AF was significantly (P<0.0001) associated with
      pneumonia, pleural effusions requiring drainage, and maximum postoperative C
      reactive protein (CRP) (P<0.05) but not with anastomotic leak/conduit necrosis or
      mortality. Amiodarone was the primary treatment in 63% of cases, 1% underwent
      cardioversion, and 92% were in sinus rhythm on discharge. At a median follow-up
      of 40 months (7-109 months), the median survival was 40 months versus 53 months
      in the AF and non-AF cohorts, respectively (P=0.353) CONCLUSIONS: New-onset AF is
      common, linked to age, diabetes, cardiac disease, and neoadjuvant therapy. It is
      strongly associated with complications, principally respiratory sepsis, and
      systemic inflammation. For most, it resolves, with no impact on oncologic
      outcomes.

PMID- 25379847
TI  - Impact of neoadjuvant chemoradiotherapy on postoperative outcomes after
      esophageal cancer resection: results of a European multicenter study.
AB  - OBJECTIVES: To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on
      anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer
      (EC) resection. BACKGROUND: Conflicting data have emerged from randomized studies
      regarding the impact of NCRT on AL. METHODS: Among 2944 consecutive patients
      operated on for EC between 2000 and 2010 in 30 European centers, patients treated
      by NCRT after surgery (n=593) were compared with those treated by primary surgery
      (n=1487). Multivariable analyses and propensity score matching were used to
      compensate for the differences in some baseline characteristics. RESULTS:
      Patients in the NCRT group were younger, with a higher prevalence of male sex,
      malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after
      2005 when compared with the primary surgery group. Postoperative AL rates were
      8.8% versus 10.6% (P=0.220), and 90-day postoperative mortality and morbidity
      rates were 9.3% versus 7.2% (P=0.110) and 33.4% versus 32.1% (P=0.564),
      respectively. Pulmonary complication rates did not differ between groups (24.6%
      vs 22.5%; P=0.291), whereas chylothorax (2.5% vs 1.2%; P=0.020), cardiovascular
      complications (8.6% vs 0.1%; P=0.037), and thromboembolic events (8.6% vs 6.0%;
      P=0.037) were higher in the NCRT group. After propensity score matching, AL rates
      were 8.8% versus 11.3% (P=0.228), with more chylothorax (2.5% vs 0.7%; P=0.030)
      and trend toward more cardiovascular and thromboembolic events in the NCRT group
      (P=0.069). Predictors of AL were high American Society of Anesthesiologists
      scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT.
      CONCLUSIONS: Neoadjuvant chemoradiotherapy does not have an impact on the AL rate
      after EC resection (NCT 01927016).

PMID- 25379849
TI  - Prognostic classification of histopathologic response to neoadjuvant therapy in
      esophageal adenocarcinoma.
AB  - OBJECTIVES: To evaluate the histopathologic response to neoadjuvant therapy in
      esophageal adenocarcinoma according to impact on prognosis and to suggest a
      classification for clinical routine. BACKGROUND: Measures of histopathologic
      response to neoadjuvant treatment of esophageal cancer such as Mandard tumor
      regression grading focus on the effect on the primary tumor. Although lymph node
      infiltration is of significant prognostic importance, this criterion is mostly
      not included in the response classifications. METHODS: A total of 370 patients
      (89% males, median age: 61 years) with neoadjuvant radiochemotherapy (40 Gy, 5
      FU, cisplatin) or chemotherapy (MAGIC or FLOT) for cT3, Nx, M0 esophageal
      adenocarcinoma were included in the analysis. All patients had undergone
      transthoracic en bloc esophagectomy, with a median of 27 resected lymph nodes and
      a R0-resection rate of 92%. Histopathologic regression grading differentiated
      major or minor response according to less or more than 10% vital cells in the
      primary tumor. The lymph nodes were classified as ypN0 or ypN+. RESULTS: From the
      patients with R0 resection and M0 category, 3 groups with significantly different
      5-year survival rates (5-YSR) could be differentiated: 1. Major response and ypN0
      (n=100) with 5-YSR of 64% 2. Either major response and ypN+ (n=34) 5-YSR 42% or
      minor response and ypN0 (n=84) 5-YSR 44%, together 42% 5-YSR 3. Minor response
      and ypN+ (n=111) and 5-YSR of 18%. CONCLUSIONS: A combined classification of
      primary tumor regression and lymph node status in 3 grades represents a simple
      and reproducible prognostic classification of the effect of neoadjuvant treatment
      in esophageal adenocarcinoma.

PMID- 25379850
TI  - Lymph node retrieval during esophagectomy with and without neoadjuvant
      chemoradiotherapy: prognostic and therapeutic impact on survival.
AB  - OBJECTIVES: We aimed to examine the association between total number of resected
      nodes and survival in patients after esophagectomy with and without nCRT.
      BACKGROUND: Most studies concerning the potentially positive effect of extended
      lymphadenectomy on survival have been performed in patients who underwent surgery
      alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear
      whether extended lymphadenectomy after nCRT is still useful. METHODS: Patients
      from the randomized CROSS-trial who completed the entire protocol (ie, surgery
      alone or chemoradiotherapy + surgery) were included. With Cox regression models,
      we compared the impact of number of resected nodes as well as resected positive
      nodes on survival in both groups. RESULTS: One hundred sixty-one patients
      underwent surgery alone, and 159 patients received multimodality treatment. The
      median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9
      21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent
      lymph node positivity after nCRT had a greater negative prognostic impact on
      survival as compared with lymph node positivity after surgery alone. The total
      number of resected nodes was significantly associated with survival for patients
      in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76;
      P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98).
      CONCLUSIONS: The number of resected nodes had a prognostic impact on survival in
      patients after surgery alone, but its therapeutic value is still controversial.
      After nCRT, the number of resected nodes was not associated with survival. These
      data question the indication for maximization of lymphadenectomy after nCRT.

PMID- 25379851
TI  - R1 rectal resection: look up and don't look down.
AB  - BACKGROUND: After rectal resection for adenocarcinoma, pathological examination
      may reveal invasion of the distal margin (DM) and/or a circumferential resection
      margin of the tumor (CRM-T) or of involved nodes (CRM-N) less than or equal to 1
      mm. Such findings transform a planned R0 resection to R1. AIM: : The aim was to
      analyze the impact of an R1 resection on prognosis, recurrence rate, and choice
      of adjuvant treatment. PATIENTS AND METHODS: All R1 resections observed between
      2006 and 2011 were retrospectively collected. Patients were matched with 80
      patients with R0 resections according to age, body mass index, gender,
      neoadjuvant treatment, type of resection, ypT/pT stages, and N stage. RESULTS:
      Among 472 rectal resections performed, 40 (8.5%) were R1 (CRM-T=34; CRM-N=11;
      invaded DM=4). Among the 4 patients with invaded DM, 3 underwent salvage
      abdominoperineal resection. Of the 12 patients who had not received neoadjuvant
      treatment, 5 received adjuvant radiotherapy. Mean follow-up was 49.3+/-29.3
      months for the 120 patients; 5-year overall survival (OS) and disease-free
      survival (DFS) were 72% and 56%. Comparison between R0 and R1 resections showed a
      trend toward worse OS in R1 resections: 62% versus 79% (P=0.0954), a
      significantly worse DFS: 41% versus 65% (P=0.0267). Local recurrence rates were
      similar: 12% versus 13% (P=0.9177), whereas distant recurrence was significantly
      more frequent after R1 resection: 56% versus 26% (P=0.0040). CONCLUSIONS: R1
      resection is associated with a worse prognosis, but local recurrence rate does
      not differ significantly from matched R0 resections. The difference was observed
      for distant recurrences, especially lung, favoring the use of chemotherapy and
      close surveillance of the thorax.

PMID- 25379852
TI  - Prolonged time to surgery after neoadjuvant chemoradiotherapy increases
      histopathological response without affecting survival in patients with esophageal
      or junctional cancer.
AB  - OBJECTIVE: To determine the relation between time to surgery (TTS) after
      neoadjuvant chemoradiotherapy (nCRT) and pathologically complete response (pCR),
      surgical outcome, and survival in patients with esophageal cancer. BACKGROUND:
      Standard treatment for potentially curable esophageal cancer is nCRT plus surgery
      after 4 to 6 weeks. In rectal cancer patients, evidence suggests that prolonged
      TTS is associated with a higher pCR rate and possibly with better survival.
      METHODS: We identified patients treated with nCRT plus surgery for esophageal
      cancer between 2001 and 2011. TTS (last day of radiotherapy to day of surgery)
      varied mainly for logistical reasons. Minimal follow-up was 24 months. The effect
      of TTS on pCR rate, postoperative complications, and survival was determined with
      (ordinal) logistic, linear, and Cox regression, respectively. RESULTS: In total,
      325 patients were included. Median TTS was 48 days (p25-p75=40-60). After 45
      days, TTS was associated with an increased probability of pCR [odds ratio
      (OR)=1.35 per additional week of TSS, P=0.0004] and a small increased risk of
      postoperative complications (OR=1.20, P<0.001). Prolonged TTS had no effect on
      disease-free and overall survivals (HR=1.00 and HR=1.06 per additional week of
      TSS, P=0.976 and P=0.139, respectively). CONCLUSIONS: Prolonged TTS after nCRT
      increases the probability of pCR and is associated with a slightly increased
      probability of postoperative complications, without affecting disease-free and
      overall survivals. We conclude that TTS can be safely prolonged from the usual 4
      to 6 weeks up to at least 12 weeks, which facilitates a more conservative wait
      and-see strategy after neoadjuvant chemoradiotherapy to be tested.

PMID- 25379853
TI  - Two-stage hepatectomy versus 1-stage resection combined with radiofrequency for
      bilobar colorectal metastases: a case-matched analysis of surgical and
      oncological outcomes.
AB  - OBJECTIVES: The aim of this study was to compare the long-term results of 2
      surgical strategies for patients with bilobar colorectal liver metastases
      (bCRLM). BACKGROUND: Two-stage hepatectomy is the surgical strategy mostly chosen
      for treating extensive BCLM with the pitfall of dropout after the first stage.
      One-stage strategy combining limited resections and radiofrequency ablation could
      be proposed as an option in this population. PATIENTS AND METHODS: Between 2000
      and 2010, 272 patients were consecutively operated in 2 expert centers practicing
      1- or 2-stage hepatectomy for bCRLM. A case-match study (1:1) was conducted using
      number and size of nodules, synchronous presentation, primary node status, and
      extrahepatic disease as matching variables to compare overall survival (OS) and
      disease-free survival (DFS). The analysis was performed in intention to treat,
      including patients who did not undergo the second stage. RESULTS: In the case
      match analysis (156 matched patients), median OS and DFS did not differ
      significantly between patients in 1- and 2-stage hepatectomy, respectively: 37.2
      and 34.5 months (P=0.6), 9.4 and 7.5 months (P=0.25). Multivariate analysis
      confirmed the absence of impact of strategy on OS and DFS. Primary advanced T
      stage and synchronous presentation were predictors of poor OS (HR=3.67 and 1.92);
      CEA more than 200 ng/mL, absence of postoperative chemotherapy, and extrahepatic
      disease were predictive of recurrence (HR=2.77, 1.85 and 1.69, respectively).
      CONCLUSIONS: This first case-match study demonstrates that on an intention-to
      treat analysis 1- and 2-stage hepatectomy in patients with bCRLM achieve
      comparable OS and DFS, despite the high dropout of the 2-stage strategy.

PMID- 25379855
TI  - ALPPS: from human to mice highlighting accelerated and novel mechanisms of liver
      regeneration.
AB  - OBJECTIVES: To develop a reproducible animal model mimicking a novel 2-staged
      hepatectomy (ALPPS: Associating Liver Partition and Portal Vein Ligation for
      Staged Hepatectomy) and explore the underlying mechanisms. BACKGROUND: ALPPS
      combines portal vein ligation (PVL) with liver transection (step I), followed by
      resection of the deportalized liver (step II) within 2 weeks after the first
      surgery. This approach induces accelerated hypertrophy of the liver remnant to
      enable resection of massive tumor load. To explore the underlying mechanisms, we
      designed the first animal model of ALPPS in mice. METHODS: The ALPPS group
      received 90% PVL combined with parenchyma transection. Controls underwent either
      transection or PVL alone. Regeneration was assessed by liver weight and
      proliferation-associated molecules. PVL-treated mice were subjected to splenic,
      renal, or pulmonary ablation instead of hepatic transection. Plasma from ALPPS
      treated mice was injected into mice after PVL. Gene expression of auxiliary
      mitogens in mouse liver was compared to patients after ALPPS or PVL. RESULTS: The
      hypertrophy of the remnant liver after ALPPS doubled relative to PVL, whereas
      mice with transection alone disclosed minimal signs of regeneration. Markers of
      hepatocyte proliferation were 10-fold higher after ALPPS, when compared with
      controls. Injury to other organs or ALPPS-plasma injection combined with PVL
      induced liver hypertrophy similar to ALPPS. Early initiators of regeneration were
      significantly upregulated in human and mice. CONCLUSIONS: ALPPS in mice induces
      an unprecedented degree of liver regeneration, comparable with humans.
      Circulating factors in combination with PVL seem to mediate enhanced liver
      regeneration, associated with ALPPS.

PMID- 25379854
TI  - Early survival and safety of ALPPS: first report of the International ALPPS
      Registry.
AB  - OBJECTIVES: To assess safety and outcomes of the novel 2-stage hepatectomy,
      Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy
      (ALPPS), using an international registry. BACKGROUND: ALPPS induces accelerated
      growth of small future liver remnants (FLR) to allow curative resection of liver
      tumors. There is concern about safety based on reports of higher morbidity and
      mortality. METHODS: A Web-based data entry system was created with password
      access and data pseudoencryption (NCT01924741). All patients with complete 90-day
      data were included. Multivariate logistic regression analysis was performed to
      identify independent risk factors for severe complications and mortality and
      volume growth of the FLR. RESULTS: Complete data were available for 202 patients.
      A total of 141 (70%) patients had colorectal liver metastases (CRLM). Median
      starting standardized future liver remnants of 21% increased by 80% within a
      median of 7 days. Ninety-day mortality was 19/202 (9%). Severe complications
      including mortalities (Clavien-Dindo>=IIIb) occurred in 27% of patients.
      Independent factors for severe complications were red blood cell transfusion
      [odds ratio (OR), 5.2), ALPPS stage I operating time greater than 300 minutes
      (OR, 4.4), age more than 60 years (OR, 3.8), and non-CRLM (OR, 2.7). Age, use of
      Pringle maneuver, and histologic changes led to less volume growth. In patients
      younger than 60 years with CRLM, 90-day mortality was similar to conventional 2
      stage hepatectomies for CRLM. CONCLUSIONS: This is the first analysis of the
      ALPPS registry showing that ALPPS has increased perioperative morbidity and
      mortality in older patients but better outcomes in patients with CRLM.

PMID- 25379856
TI  - Pancreatic main-duct involvement in branch-duct IPMNs: an underestimated risk.
AB  - OBJECTIVES: This study aimed to analyze a large single-center population of
      resected intraductal papillary mucinous neoplasms (IPMN) of the pancreas with
      respect to risk factors of malignant transformation. BACKGROUND: There is
      international consensus that main-duct (MD) as well as mixed-type IPMNs should be
      treated surgically due to a high risk of malignancy. In contrast, there is an
      ongoing controversy about surgery of branch-duct type IPMN (BD-IPMN). METHODS:
      All consecutive patients who underwent surgery for IPMN between January 2004 and
      December 2012 were included. Clinical characteristics and preoperative imaging
      were correlated with histopathological features. RESULTS: A total of 512 patients
      underwent pancreatic surgery and had a histological proof of IPMN. According to
      preoperative imaging, 74 patients had MD-IPMN (14%), 205 mixed-type (40%), and
      233 suspected BD-IPMN (46%). On histopathology, 162 of 512 patients revealed low
      grade, 105 moderate, and 52 high-grade dysplasia. One hundred ninety-three IPMN
      patients (38%) suffered from invasive carcinoma. Among invasive IPMNs, the
      majority (58%) were mixed-type lesions according to preoperative imaging. Of 141
      Sendai negative BD-IPMNs, a malignancy rate of 18% (high-grade dysplasia and
      invasive carcinoma) was found. Most interesting, 29% of suspected BD-IPMNs
      (67/233) revealed histological involvement of the main pancreatic duct not
      evident in preoperative imaging. CONCLUSIONS: All subtypes of IPMNs display a
      relevant risk for malignant transformation. By abdominal imaging, many IPMNs are
      misclassified as BD-IPMNs but reveal mixed-type lesions in histopathology.
      Because currently available preoperative diagnostics are not sufficient to
      reliably diagnose BD-IPMNs, surgical resection for suspected small branch-duct
      IPMN should be considered in patients fit for surgery.

PMID- 25379857
TI  - Resection of liver metastases from colorectal mucinous adenocarcinoma: is this a
      different disease? Results of a case-control study.
AB  - OBJECTIVES: To compare outcomes following liver resection of colorectal
      metastases (CRLM) from mucinous adenocarcinoma (Muc-CRLM) versus nonmucinous
      adenocarcinoma (non-Muc-CRLM). BACKGROUND: Among colorectal adenocarcinomas, 10%
      15% are mucinous and have worse prognoses than nonmucinous ones. Outcomes of
      liver resection for Muc-CRLM remain unknown. METHODS: Among 701 patients
      undergoing liver resection for CRLM between 1998 and 2012, 102 (14.6%) had Muc
      CRLM. Each was matched with a non-Muc-CRLM patient, based on tumor N status,
      disease-free interval (DFI) between primary tumor and metastases, CRLM number and
      diameter, extrahepatic disease, and preoperative chemotherapy. RESULTS: Within
      the 2 groups, 69.6% of patients had N+ primary tumor, 72.5% had DFI of less than
      12 months, 28.4% had 4 or more CRLM, and 22.5% had associated extrahepatic
      disease. 59.8% of patients received preoperative chemotherapy. Muc-CRLM patients
      had higher prevalences of right/transverse colon cancer (55.9% vs 29.4%;
      P<0.0001) and K-ras mutation (67 patients tested, 61.8% vs 36.4%; P=0.037), as
      well as lower response to preoperative chemotherapy (63.9% vs 85.2%; P=0.006).
      Multivariate analysis showed Muc-CRLM to have lower rates of 5-year overall
      (33.2% vs 55.2%; P=0.010) and disease-free survival (32.5% vs 49.3%; P=0.037).
      Muc-CRLM recurrence was more often peritoneal (20.3% vs 6.5%; P=0.024) and at
      multiple sites (47.5% vs 21.0%; P=0.002), and had lower rates of re-resection
      (16.9% vs 43.5%; P=0.002) and 3-year post-recurrence survival (11.7% vs 43.4%;
      P=0.0003). CONCLUSIONS: Muc-CRLM patients strongly differed from non-Muc-CRLM
      patients, showing a lower chemotherapy response and higher K-ras mutation
      prevalence. Muc-CRLM appears to be a separate disease, which is associated with
      worse survival and aggressive rarely re-resectable recurrences.

PMID- 25379858
TI  - Is minimal, [almost] steroid-free immunosuppression a safe approach in adult
      liver transplantation? Long-term outcome of a prospective, double blind, placebo
      controlled, randomized, investigator-driven study.
AB  - OBJECTIVE: To investigate the safety of minimal immunosuppression (IS) in liver
      transplantation (LT). BACKGROUND: The lack of long-term follow-up studies,
      including pathologic data, has led to a protean handling of IS in LT. METHODS:
      Between February 2000 and September 2004, 156 adults were enrolled in a
      prospective, randomized, double-blind, placebo-controlled minimization trial
      comparing tacrolimus placebo (TAC-PLAC) and TAC short-term steroid (TAC-STER) IS.
      All patients had a minimum clinical, biochemical, and histological follow-up of 5
      years. RESULTS: Five-year actual patient and graft survival rates in TAC-PLAC and
      TAC-STER groups were 78.1% and 82.1% (P=0.89) and 74.2% and 76.9% (P=0.90),
      respectively. Five-year biopsies were available in 112 (89.6%) of 125 survivors.
      Twelve patients refused a biopsy because of their excellent evolution; tissue
      material was insufficient in 1 patient; 11 had normal liver tests; and 2 patients
      had developed alcoholic and secondary biliary cirrhosis. Histology was normal in
      44 (39.3%) patients; 35 (31.3%) had disease recurrence. The remaining biopsies
      showed nonspecific chronic hepatitis (14.3%), mild inflammatory infiltrates
      (10.7%), and steatosis (3.5%). All findings were equally distributed between both
      groups. In each group, 3 patients (4.8%) presented with acute cellular rejection
      after the first year and only 1 (0.9%) TAC-PLAC patient developed chronic
      rejection after IS withdrawal because of pneumonitis. Arterial hypertension,
      diabetes mellitus, renal insufficiency, hypercholesterolemia, gout, and obesity
      were equally low in both groups. CONCLUSIONS: Excellent long-term results can be
      obtained under minimal IS and absence of steroids. TAC-based monotherapy is
      feasible in most adult liver recipients until 5 years of follow-up.

PMID- 25379859
TI  - Roux-en-Y gastric bypass versus adjustable gastric banding to reduce nonalcoholic
      fatty liver disease: a 5-year controlled longitudinal study.
AB  - OBJECTIVES: To compare the long-term benefit of gastric bypass [Roux-en-Y gastric
      bypass (RYGB)] versus adjustable gastric banding (AGB) on nonalcoholic fatty
      liver disease (NAFLD) in severely obese patients. BACKGROUND: NAFLD improves
      after weight loss surgery, but no histological study has compared the effects of
      the various bariatric interventions. METHODS: Participants consisted of 1236
      obese patients (body mass index=48.4+/-7.6 kg/m), enrolled in a prospective
      longitudinal study for up to 5 years after RYGB (n=681) or AGB (n=555). Liver
      biopsy samples were available for 1201 patients (97.2% of those at risk) at
      baseline, 578 patients (47.2%) at 1 year, and 413 patients (68.9%) at 5 years.
      RESULTS: At baseline, NAFLD was present in 86% patients and categorized as severe
      [NAFLD activity score (NAS)>=3] in 22% patients. RYGB patients had a higher body
      mass index (49.8+/-8.2 vs 46.8+/-6.5 kg/m, P<0.001) and more severe NAFLD (NAS:
      2.0+/-1.5 vs 1.7+/-1.4, P=0.004) than AGB patients. Weight loss at 5 years was
      25.5%+/-11.8% after RYGB versus 21.4%+/-12.7% after AGB (P<0.001). When analyzed
      with a mixed model, all NAFLD parameters improved after surgery (P<0.001) and
      improved significantly more after RYGB than after AGB [steatosis (%): 1 year,
      7.9+/-13.7 vs 17.9+/-21.5, P<0.001/5 years, 8.7+/-7.1 vs 14.5+/-20.8, P<0.05;
      NAS: 1 year, 0.7+/-1.0 vs 1.1+/-1.2, P<0.001/5 years, 0.7+/-1.2 vs 1.0+/-1.3,
      P<0.05]. In multivariate analysis, the superiority of RYGB was primarily but not
      entirely explained by weight loss. CONCLUSIONS: The improvement of NAFLD was
      superior after RYGB than after AGB.

PMID- 25379860
TI  - The impact of neural invasion severity in gastrointestinal malignancies: a
      clinicopathological study.
AB  - OBJECTIVES: Because neural invasion (NI) is still inconsistently reported and not
      well characterized within gastrointestinal malignancies (GIMs), our aim was to
      determine the exact prevalence and severity of NI and to elucidate the true
      impact of NI on patient's prognosis. BACKGROUND: The union internationale contre
      le cancer (UICC) recently added NI as a novel parameter in the current TNM
      classification. However, there are only a few existing studies with specific
      focus on NI, so that the distinct role of NI in GIMs is still uncertain.
      MATERIALS AND METHODS: NI was characterized in approximately 16,000 hematoxylin
      and eosin tissue sections from 2050 patients with adenocarcinoma of the
      esophagogastric junction (AEG)-I-III, squamous cell carcinoma (SCC) of the
      esophagus, gastric cancer (GC), colon cancer (CC), rectal cancer (RC),
      cholangiocellular cancer (CCC), hepatocellular cancer (HCC), and pancreatic
      cancer (PC). NI prevalence and severity was determined and related to patient's
      prognosis and survival. RESULTS: NI prevalence largely varied between HCC/6%,
      CC/28%, RC/34%, AEG-I/36% and AEG-II/36%, SCC/37%, GC/38%, CCC/58%, and AEG
      III/65% to PC/100%. NI severity score was uppermost in PC (24.9+/-1.9) and lowest
      in AEG-I (0.8+/-0.3). Multivariable analyses including age, sex, TNM stage, and
      grading revealed that the prevalence of NI was significantly associated with
      diminished survival in AEG-II/III, GC, and RC. However, increasing NI severity
      impaired survival in AEG-II/III and PC only. CONCLUSIONS: NI prevalence and NI
      severity strongly vary within GIMs. Determination of NI severity in GIMs is a
      more precise tool than solely recording the presence of NI and revealed dismal
      prognostic impact on patients with AEG-II/III and PC. Evidently, NI is not a
      concomitant side feature in GIMs and, therefore, deserves special attention for
      improved patient stratification and individualized therapy after surgery.

PMID- 25379861
TI  - Gastroesophageal reflux disease and laparoscopic sleeve gastrectomy: a
      physiopathologic evaluation.
AB  - OBJECTIVE: To evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on
      gastroesophageal reflux disease (GERD) in morbidly obese patients. BACKGROUND:
      Symptomatic GERD is considered by many a contraindication to LSG. However,
      studies evaluating the relationship between LSG and GERD by 24-hour pH monitoring
      are lacking. METHODS: Consecutive morbidly obese patients selected for LSG were
      included in a prospective clinical study. Gastroesophageal function was evaluated
      using a clinical validated questionnaire, upper endoscopy, esophageal manometry,
      and 24-hour pH monitoring before and 24 months after LSG. This trial is
      registered with ClinicalTrials.gov (no. NCT02012894). RESULTS: From June 2009 to
      September 2011, a total of 71 patients were enrolled into the study; 65 (91.5%)
      completed the 2-year protocol. On the basis of preoperative 24-hour pH
      monitoring, patients were divided into group A (pathologic, n=28) and group B
      (normal, n=37). Symptoms improved in group A, with the Gastroesophageal Reflux
      Disease Symptom Assessment Scale score decreasing from 53.1+/-10.5 to 13.1+/-3.5
      (P<0.001). The DeMeester score and total acid exposure (% pH<4) decreased in
      group A patients (DeMeester score from 39.5+/-16.5 to 10.6+/-5.8, P<0.001; % pH<4
      from 10.2+/-3.7 to 4.2+/-2.6, P<0.001). Real "de novo" GERD occurred in 5.4%
      group B patients. No significant changes in lower esophageal sphincter pressure
      and esophageal peristalsis amplitude were found in both groups. CONCLUSIONS: LSG
      improves symptoms and controls reflux in most morbidly obese patients with
      preoperative GERD. In obese patients without preoperative evidence of GERD, the
      occurrence of "de novo" reflux is uncommon. Therefore, LSG should be considered
      an effective option for the surgical treatment of obese patients with GERD.

PMID- 25379862
TI  - "Surgeons' intuition" versus "prognostic models": predicting the risk of liver
      resections.
AB  - OBJECTIVES: Analyze surgeons' anticipation of the risk of hepatectomy.
      BACKGROUND: Risk prediction enables adequate counseling and improves safety.
      Models are available that predict postoperative morbidity and length of stay
      (LOS), but their performance is ill-defined. Surgeons' ability to predict these
      endpoints is unknown. METHODS: This prospectively designed, multicenter trial
      included all adult patients undergoing elective hepatectomy. Primary endpoints
      were 90-day morbidity and mortality and LOS. Explanatory variables included (i)
      "surgeons' intuition" (surgeons' anticipation) of the difficulty of the
      procedure, postoperative morbidity, and LOS and (ii) "prognostic models" (models
      based on objective clinic-biological variables) available at the time of
      anticipation. The performance of "surgeons' intuition" and "prognostic models"
      was assessed by area under the receiver operating characteristic curve and its
      accuracy by the diagnostic odd ratios. RESULTS: Between October 2012 and
      September 2013, 946 patients operated on in hepato-pancreatico-biliary units in 9
      teaching hospitals by 26 surgeons were enrolled. Mortality, morbidity, and median
      LOS were 3.3%, 49.4%, and 8 days, respectively. Preoperative surgeons' intuition
      of difficulty correlated with actual difficulty (Kendall tau=0.97; P=0.0001) but
      not with morbidity (Kendall tau=0.01; P=0.0006) or LOS (Kendall tau=0.10;
      P=0.004). Morbidity was predicted accurately in 38.8% of patients and
      underestimated in 38.2%. Anticipation of LOS was accurate (+/-2 days) in 30.0%
      and underestimated in 47.1%. The accuracies and performance of preoperative and
      postoperative "surgeons' intuition" were not different and were not different
      between centers or surgeons' experience. The accuracy of "prognostic models" was
      significantly greater than that of anticipations and not improved by adding
      "anticipations" to the model. CONCLUSIONS: Surgeons should be aware of the
      limited accuracy of their intuition.

PMID- 25379863
TI  - Pulmonary valvotomy with echocardiographic guidance in neonates with pulmonary
      atresia and intact ventricular septum.
AB  - BACKGROUND: Percutaneous transcatheter valvotomy of the atretic pulmonary valve
      (PV) carries a risk of perforation of the right ventricle (RV) and requires
      standby of the cardiac surgical team for potential emergent cardiac management.
      The objective of this study was to introduce a successful and safe transcatheter
      wire perforation of the atretic PV using echocardiographic guidance in neonates
      with pulmonary atresia and an intact ventricular septum. METHODS: In addition to
      fluoroscopic guidance, echocardiography was used throughout the procedure. For
      positioning the Judkins right (JR) catheter at the point of 'tenting' indicating
      center of the PV, the morphology and position of the PV were confirmed using a
      left-tilted parasternal long axis view and a slight counterclockwise-rotated
      parasternal short axis view. After the JR catheter was positioned at the point of
      tenting of the atretic PV, the stiff end of the 0.014 mm PTCA wire was advanced
      through the PV toward the main pulmonary artery using echocardiographic guidance.
      During the first portion of the procedure, accurate perforation using
      echocardiographic imaging was confirmed. After then, pulmonary valvuloplasty with
      increasingly larger balloons, beginning with an initial 2.5 * 20 mm(2) PTCA
      balloon and finishing with a final 8 * 20 mm(2) PTA balloon was performed.
      RESULTS: In all patients, successful valve perforation and balloon valvuloplasty
      were achieved. There were no significant cardiac complications, including
      perforation of the RV. CONCLUSIONS: Pulmonary valvotomy using transthoracic
      echocardiographic guidance can reduce the risk of perforation of the RV and be
      more successful compared with that using only fluoroscopic guidance.

PMID- 25379864
TI  - Breast cancer chemoprevention by dietary natural phenolic compounds: specific
      epigenetic related molecular targets.
AB  - Breast cancer is a systemic malignant disease that is a major cause of cancer
      related death among women worldwide. Recently, multiple lines of evidence from
      epidemiologic studies have suggested that epigenetic and genetic changes are
      involved in breast cancer development. In breast cancer patients, hormone
      receptor status, breast cancer stem-like cell population, and tumor
      microenvironment are reflective of breast cancer progression, drug resistance,
      and tumor recurrence. Strong relationships between a phytochemical-rich diet and
      a reversal of epigenetic alterations and/or modulated signaling pathways of
      carcinogenesis (initiation, promotion, and progression) suggest a potential
      approach for preventing breast cancer. Additionally, dietary consumption of
      natural phenolic compounds containing phytoestrogen properties exerts beneficial
      effects in breast cancer chemoprevention. In this review, we summarize the
      specific chemopreventive targets of representative phenolic compounds with an
      emphasis on their efficacy at interfering with epigenetic event related hormonal
      and nonhormonal signaling cascades that are responsible for multistage breast
      carcinogenesis. 

PMID- 25379865
TI  - A multimeric carcinoembryonic antigen signal inhibits the activation of human T
      cells by a SHP-independent mechanism: a potential mechanism for tumor-mediated
      suppression of T-cell immunity.
AB  - Carcinoembryonic antigen (CEA) is a well-known tumor antigen that is found in the
      serum of patients with various cancers and is correlated with an increased risk
      of cancer recurrence and metastasis. To understand the tumor environment and to
      develop antitumor therapies, CEA has been studied as an antigen to
      activate/tolerate specific T cells. In this study, we show that CEA can function
      as a coinhibitory molecule and can inhibit the activation of human peripheral
      blood mononucleated cell-derived T cells. The addition of CEA-overexpressing
      tumor cells or immobilized CEA dampened both cell proliferation and the
      expression of IL-2 and CD69 expression in T cells after TCR stimulation. The
      phosphorylation of ERK and translocation of NFAT were hampered in these cells,
      whereas the phosphorylation of proximal TCR signaling molecules such as ZAP70 and
      phospholipase Cgamma was not affected by immobilized CEA. To determine the
      relevance of carcinoembryonic antigen-related cell adhesion molecule-1 and Src
      homology region 2 domain-containing phosphatase (SHP) molecules to CEA-mediated
      suppression, we tested the effect of the SHP inhibitor, NSC-87877, on CEA
      mediated suppression of T cells; however, it did not reverse the effect of CEA.
      Collectively, these results indicate that CEA can function as a modulator of T
      cell responses suggesting a novel mechanism of tumor evasion. 

PMID- 25379866
TI  - Hydration and ion pair formation in common aqueous La(III) salt solutions--a
      Raman scattering and DFT study.
AB  - Raman spectra of aqueous lanthanum perchlorate, triflate (trifluorosulfonate),
      chloride and nitrate solutions were measured over a broad concentration (0.121
      3.050 mol L(-1)) range at room temperature (23  degrees C). A very weak mode at
      343 cm(-1) with a full width at half height at 49 cm(-1) in the isotropic
      spectrum suggests that the nona-aqua La(III) ion is thermodynamically stable in
      dilute perchlorate solutions (~0.2 mol L(-1)) while in concentrated perchlorate
      solutions outer-sphere ion pairs and contact ion pairs are formed. The La(3+)
      nona-hydrate was also detected in a 1.2 mol L(-1) La(CF3SO3)3(aq). In lanthanum
      chloride solutions chloro-complex formation was detected over the measured
      concentration range from 0.5-3.050 mol L(-1). The chloro-complexes in LaCl3(aq)
      are fairly weak and disappear with dilution. At a concentration <0.1 mol L(-1)
      almost all complexes disappeared. In LaCl3 solutions, with additional HCl, a
      series of chloro-complexes of the type [La(OH2)(9-n)Cln](+3-n) (n = 1-3) were
      formed. The La(NO3)3(aq) spectra were compared with a spectrum of a 0.409 mol L(
      1) NaNO3(aq) and it was concluded that in La(NO3)3(aq) over the concentration
      range from 0.121-1.844 mol L(-1), nitrato-complexes, [La(OH2)(9-n)(NO3)n](+3-n)
      (n = 1, 2) were formed. These nitrato-complexes are quite weak and disappear with
      dilution <0.01 mol L(-1). DFT geometry optimizations and frequency calculations
      are reported for a lanthanum-nona-hydrate with a polarizable dielectric continuum
      in order to take the solvent into account. The bond distances and angles for the
      cluster geometry of [La(OH2)9](3+) with the polarizable dielectric continuum are
      in good agreement with data from recent structural experimental measurements and
      high quality simulations. The DFT frequency of the La-O stretching mode at 328.2
      cm(-1), is only slightly smaller than the experimental one.

PMID- 25379867
TI  - Lignans from the bark of Zanthoxylum simulans.
AB  - Investigation on the EtOAc extract of the bark of Zanthoxylum simulans led to the
      isolation of four new lignans including zanthoxylumin A (1), zanthoxylumin B (2),
      ( - )-magnolin (3), and ( - )-pinoresinol-di-3,3-dimethylallyl ether (4). Their
      structures were established by comprehensive analysis of the spectral data,
      especially 1D and 2D NMR spectra. 

PMID- 25379868
TI  - Descemet membrane endothelial keratoplasty in vitrectomized eyes: clinical
      results.
AB  - PURPOSE: The aim of this study was to evaluate clinical outcomes of Descemet
      membrane endothelial keratoplasty (DMEK) in vitrectomized eyes. METHODS: Medical
      records were reviewed for demographics, baseline and follow-up best spectacle
      corrected visual acuities (BCVAs), endothelial cell densities, and indication for
      DMEK. Operative notes were analyzed to identify any specific intraoperative
      event. RESULTS: A total of 281 DMEK cases were reviewed. Twenty cases were
      considered eligible for the study. Seven eyes had a history of anterior
      vitrectomy, and 13 eyes had a history of complete removal of the vitreous body.
      Ages ranged from 37 to 78 years (mean, 62.9 years) and mean follow-up after DMEK
      was 11.2 months (range, 3-29 months). The preoperative mean BCVA was 1.4 +/- 0.5
      logarithm of minimum angle of resolution (logMAR) and increased to 1.0 +/- 0.5
      logMAR after 4 weeks (P = 0.0290). After 6-month and 12-month follow-up, BCVA was
      0.8 +/- 0.6 logMAR (P = 0.0055) and 0.6 +/- 0.3 logMAR (P = 0.0001),
      respectively. All cases had ocular comorbidities affecting the BCVA. In 13 cases,
      significant intraoperative complications were experienced. In the immediate
      postoperative period, iatrogenic primary graft failure was reported in 2 eyes
      (2/20). In 4 eyes, late graft failure was observed. Two eyes had exacerbation of
      preexisting glaucoma. Mean preoperative endothelial cell density was 2301 +/- 159
      cells per square millimeter; postoperative follow-up visits at 6 and 12 months
      showed a decrease to 1398 +/- 161 cells per square millimeter and 1241 +/- 155
      cells per square millimeter, respectively. CONCLUSIONS: DMEK seems to be
      successful in restoring visual acuity even in vitrectomized eyes. Nevertheless,
      the overall complication rate was higher than that in standard DMEK.

PMID- 25379869
TI  - Clinical and ultrastructural characteristics of graft failure in DMEK: 1-year
      results after repeat DMEK.
AB  - PURPOSE: To evaluate the role of preexisting corneal pathology on the outcome of
      Descemet membrane endothelial keratoplasty (DMEK), and also to evaluate the long
      term outcome of repeat DMEK for graft failure after primary DMEK. METHODS:
      Eighteen patients undergoing repeat DMEK after failed DMEK were enrolled; 9 of 18
      patients had successful primary DMEK on the fellow eye. Evaluations included
      preoperative anterior chamber depth, intraoperative degree of difficulty,
      transmission electron microscopy images (n = 14), best-corrected visual acuity
      (BCVA), endothelial cell density, central corneal thickness, corneal volume, and
      patient satisfaction. RESULTS: Surgeries that led to graft failure had a higher
      intraoperative degree of difficulty compared with successful surgeries (P =
      0.002). Eight of 14 failed grafts showed ultrastructural abnormalities, that is,
      inclusions or deposits of abnormal fibrillar material in Descemet membrane,
      indicating endothelial dysfunction before transplantation. BCVA on day 10 after
      surgery was worse in eyes with graft failure compared with successful DMEK (P =
      0.008). Median BCVA (logarithm of the minimum angle of resolution) improved from
      0.5 before DMEK and 1.9 before repeat DMEK to 0.3 at 1-year follow-up (P =
      0.011). One year after repeat DMEK, endothelial cell density (cells/mm2) of donor
      corneas decreased from 2501 +/- 264 to 1373 +/- 270 (P < 0.001), central corneal
      thickness (um) decreased from 807 +/- 160 to 576 +/- 178 (P = 0.002), and corneal
      volume (mm3) decreased from 84.1 +/- 13.0 to 64.4 +/- 12.5 (P = 0.002). Patient
      satisfaction showed no difference between primary and repeat DMEK. CONCLUSIONS: A
      preexisting subclinical corneal endothelial dysfunction may contribute to primary
      DMEK failure. Repeat DMEK can be performed safely with good long-term outcome.

PMID- 25379870
TI  - Topographic and biomechanical evaluation of cornea in patients with acromegaly.
AB  - PURPOSE: The aim of this study was to compare topographic and biomechanical
      properties of corneas in patients with acromegaly with those of healthy
      individuals. METHODS: Thirty-five patients with acromegaly (study group) and 35
      healthy individuals (control group) were enrolled in this prospective study.
      Topographic measurements, including central corneal thickness (CCT), mean
      keratometry (K) value, K1, K2, surface asymmetry index, corneal volume (CV), and
      anterior chamber depth in the right eye of each participant were obtained using a
      Scheimpflug camera with a Placido disc topographer (Sirius; Costruzione Strumenti
      Oftalmici). Corneal hysteresis (CH), corneal resistance factor (CRF), corneal
      compensated intraocular pressure (IOP), and Goldmann-corelated intraocular
      pressure (IOPg) were measured using Reichert Ocular Response Analyzer (Reichert
      Ophthalmic Instruments). RESULTS: Mean CCT, CV, CH, CRF, and IOPg values were
      higher in acromegalic eyes (549.3 +/- 30.2 MUm, 59.1 +/- 3.1 MUm, 11.3 +/- 1.2 mm
      Hg, 11.3 +/- 1.2 mm Hg, and 17.5 +/- 2.9 mm Hg, respectively) than in healthy
      eyes (531.4 +/- 33.6 MUm, 57.4 +/- 2.7 MUm, 10.4 +/- 1.2 mm Hg, 10.2 +/- 1.6 mm
      Hg, and 14.8 +/- 3.1 mm Hg, respectively; CCT, P = 0.042; CV, P = 0.032; CH, P =
      0.044; CRF, P = 0.035; IOPg, P < 0.001). CONCLUSIONS: CCT, CV, CH, CRF, IOPg, and
      IOP with Goldmann applanation tonometry were significantly higher in acromegalic
      eyes. These corneal topographic and biomechanical properties, disease duration,
      and disease status should be considered when planning corneal refractive surgery
      and determining accurate intraocular pressure in patients with acromegaly.

PMID- 25379871
TI  - High-intensity (accelerated) corneal collagen cross-linking for keratoconus.

PMID- 25379872
TI  - Accelerated (9 mW/cm2) corneal collagen crosslinking for keratoconus--a 1-year
      follow-up.

PMID- 25379876
TI  - Computational studies of the gas-phase thermochemical properties of modified
      nucleobases.
AB  - In this Synopsis, we highlight some recent computational studies of the gas-phase
      thermochemical properties of modified nucleobases. Although this field is
      relatively nascent, we aim herein to show a few examples of insights that have
      already been gained by gas-phase calculations. We focus on modified nucleobases
      that are substrates for enzymes that excise damaged bases from DNA. Because these
      enzymes have hydrophobic active sites, calculations in the "ultimate" nonpolar
      environment of the gas phase prove to be particularly relevant, providing insight
      into enzyme mechanism. 

PMID- 25379877
TI  - Nocturnal enuresis and nocturia, differences and similarities - lessons to learn?
AB  - This review highlights the current views on and differences and similarities
      between nocturnal enuresis (NE) in children and nocturia in adults, which might
      be a guidance to elucidate the missing links in our knowledge. In both
      conditions, a genetic factor is suspected. Reduced bladder capacity and nocturnal
      polyuria are the main underlying lower urinary tract-related conditions. There is
      a link with sleep disorders, although it is not clear whether this is a cause or
      consequence. Physical and mental health are comprised in both conditions,
      however, in different ways. In NE, constipation and attention deficit disorder
      are the most important comorbidities and the effect on mental health and quality
      of life is mainly through the negative impact on self-esteem. In nocturia,
      cardiovascular disease and fall injuries are important comorbidities, mainly
      affecting the older nocturia population; personal distress and depression are
      consequences of the related poor sleep quality. For both conditions, treatment is
      often inadequate and a more individualized approach seems to be necessary. The
      main difference between NE and nocturia seems to be the difference in arousal to
      bladder stimuli, suggesting that sleep characteristics might be a key factor in
      these conditions. 

PMID- 25379878
TI  - Mimicking the hierarchical functions of dentin collagen cross-links with plant
      derived phenols and phenolic acids.
AB  - Proanthocyanidins (PACs) are secondary plant metabolites that mediate
      nonenzymatic collagen cross-linking and enhance the properties of collagen based
      tissue, such as dentin. The extent and nature of cross-linking is influenced by
      the composition and specific chemical structure of the bioactive compounds
      present in certain PAC-rich extracts. This study investigated the effect of the
      molecular weight and stereochemistry of polyphenol compounds on two important
      properties of dentin, biomechanics, and biostability. For that, purified phenols,
      a phenolic acid, and some of its derivatives were selected: PAC dimers (A1, A2,
      B1, and B2) and a trimer (C1), gallic acid (Ga), its esters methyl-gallate (MGa)
      and propyl-gallate (PGa), and a pentagalloyl ester of glucose (PGG). Synergism
      was assessed by combining the most active PAC and gallic acid derivative.
      Mechanical properties of dentin organic matrix were determined by the modulus of
      elasticity obtained in a flexural test. Biostability was evaluated by the
      resistance to collagenase degradation. PACs significantly enhanced dentin
      mechanical properties and decreased collagen digestion. Among the gallic acid
      derivatives, only PGG had a significant enhancing effect. The lack of observed
      C1:PGG synergy indicates that both compounds have similar mechanisms of
      interaction with the dentin matrix. These findings reveal that the molecular
      weight of polyphenols have a determinant effect on their interaction with type I
      collagen and modulates the mechanism of cross-linking at the molecular,
      intermolecular, and inter-microfibrillar levels. 

PMID- 25379879
TI  - Formation and dynamics of "waterproof" photoluminescent complexes of rare earth
      ions in crowded environment.
AB  - Understanding behavior of rare-earth ions (REI) in crowded environments is
      crucial for several nano- and bio-technological applications. Evolution of REI
      photoluminescence (PL) in small compartments inside a silica hydrogel, mimic to a
      soft matter bio-environment, has been studied and explained within a solvation
      model. The model uncovered the origin of high PL efficiency to be the formation
      of REI complexes, surrounded by bile salt (DOC) molecules. Comparative study of
      these REI-DOC complexes in bulk water solution and those enclosed inside the
      hydrogel revealed a strong correlation between an up to 5*-longer lifetime of
      REIs and appearance of the DOC ordered phase, further confirmed by dynamics of
      REI solvation shells, REI diffusion experiments and morphological
      characterization of microstructure of the hydrogel. 

PMID- 25379881
TI  - Direct C-H difluoromethylenephosphonation of arenes and heteroarenes with
      bromodifluoromethyl phosphonate via visible-light photocatalysis.
AB  - This communication reports a room temperature visible-light-driven protocol for
      the C-H difluoromethylenephosphonation of arenes and heteroarenes. Using
      commercially available diethyl bromodifluoromethyl phosphonate as a precursor of
      difluoromethyl radical, fac-Ir(ppy)3 as a photosensitizer and a 3 W blue LED as a
      light source, an array of aromatic compounds containing
      difluoromethylenephosphonyl groups were prepared directly from the corresponding
      arenes and heteroarenes in excellent to moderate yields. 

PMID- 25379880
TI  - Theranostic probe for simultaneous in vivo photoacoustic imaging and confined
      photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model.
AB  - Here, we report that polyethylene glycol (PEG)-coated copper(II) sulfide
      nanoparticles (PEG-CuS NPs) with their peak absorption tuned to 1064 nm could be
      used both as a contrast agent for photoacoustic tomographic imaging of mouse
      tumor vasculature and as a mediator for confined photothermolysis of tumor cells
      in an orthotopic syngeneic 4T1 breast tumor model. PEG-CuS NPs showed stronger
      photoacoustic signal than hollow gold nanospheres and single-wall carbon
      nanotubes at 1064 nm. MicroPET imaging of 4T1 tumor-bearing mice showed a gradual
      accumulation of the NPs in the tumor over time. About 6.5% of injected dose were
      taken up in each gram of tumor tissue at 24 h after intravenous injection of
      (64)Cu-labeled PEG-CuS NPs. For both photoacoustic imaging and therapeutic
      studies, nanosecond (ns)-pulsed laser was delivered with Q-switched Nd:YAG at a
      wavelength of 1064 nm. Unlike conventional photothermal ablation therapy mediated
      by continuous wave laser with which heat could spread to the surrounding normal
      tissue, interaction of CuS NPs with short pulsed laser deliver heat rapidly to
      the treatment volume keeping the thermal damage confined to the target tissues.
      Our data demonstrated that it is possible to use a single-compartment
      nanoplatform to achieve both photoacoustic tomography and highly selective tumor
      destruction at 1064 nm in small animals.

PMID- 25379882
TI  - Improving efficiency and decreasing scanning time of sonographic examination of
      the shoulder by using a poster illustrating proper shoulder positioning to the
      patient.
AB  - PURPOSE: Patients often have difficulty performing the various movements required
      for ideal positioning to enable accurate sonographic (US) assessment of the
      shoulder; this may result from pain and or unclear oral instructions. We
      performed this study to ascertain whether the use of a poster depicting the
      positions required during the examination would decrease scanning time and hence
      improve the overall efficiency of shoulder US. METHODS: We retrospectively
      compared results from 50 consecutive patients who underwent US examination
      without (group 1) and 50 with (group 2) the use of an illustrative poster
      produced by the European Society of Musculoskeletal Radiology. The difference in
      mean scanning time between the two groups was analyzed with Student's two-tailed
      t test. RESULTS: There was a statistically significant difference in scanning
      time between the two groups (group 1: 3 minutes and 5 seconds versus group 2: 2
      minutes and 9 seconds; p < 0.0001). The patients in group 2, especially those who
      had hearing difficulty, found the poster useful. CONCLUSIONS: The use of a poster
      illustrating positioning of the shoulder during an US examination is an effective
      way to improve patient compliance and significantly decreases scanning time.

PMID- 25379883
TI  - Anticancer properties of extracts from Opuntia humifusa against human cervical
      carcinoma cells.
AB  - In this study, we found that the total polyphenol and ascorbic acid levels in the
      fruit of Opuntia humifusa are higher than those in other parts of the plant. We
      further hypothesized that antioxidants in O. humifusa might affect the growth or
      survival of cancer cells. Hexane extracts of seeds and ethyl acetate extracts of
      fruits and stems significantly suppressed the proliferation of HeLa cervical
      carcinoma cells, but did not affect the proliferation of normal human BJ
      fibroblasts. Additionally, the extracts of O. humifusa induced G1 phase arrest in
      HeLa cells. The O. humifusa extracts reduced the levels of G1 phase-associated
      cyclin D1, cyclin-dependent kinase 4 (Cdk4), and phosphorylated retinoblastoma
      proteins. Moreover, p21(WAF1/Cip1) and p53 expression significantly increased
      after treatment. We examined the effects of ethyl acetate extracts of O. humifusa
      fruit (OHF) on HeLa cells xenograft tumor growth. OHF treatment significantly
      reduced tumor volume and this decrease was correlated with decreased Cdk4 and
      cyclin D1 expression. Furthermore, flavonoids, trans Taxifolin, and
      dihydrokaempferol, were isolated from OHF. Thus, this extract may be a promising
      candidate for treating human cervical carcinoma.

PMID- 25379884
TI  - A transparent and transferable framework for tracking quality information in
      large datasets.
AB  - The ability to evaluate the validity of data is essential to any investigation,
      and manual "eyes on" assessments of data quality have dominated in the past. Yet,
      as the size of collected data continues to increase, so does the effort required
      to assess their quality. This challenge is of particular concern for networks
      that automate their data collection, and has resulted in the automation of many
      quality assurance and quality control analyses. Unfortunately, the interpretation
      of the resulting data quality flags can become quite challenging with large data
      sets. We have developed a framework to summarize data quality information and
      facilitate interpretation by the user. Our framework consists of first compiling
      data quality information and then presenting it through 2 separate mechanisms; a
      quality report and a quality summary. The quality report presents the results of
      specific quality analyses as they relate to individual observations, while the
      quality summary takes a spatial or temporal aggregate of each quality analysis
      and provides a summary of the results. Included in the quality summary is a final
      quality flag, which further condenses data quality information to assess whether
      a data product is valid or not. This framework has the added flexibility to allow
      "eyes on" information on data quality to be incorporated for many data types.
      Furthermore, this framework can aid problem tracking and resolution, should
      sensor or system malfunctions arise. 

PMID- 25379885
TI  - Weight-bearing MR imaging as an option in the study of gravitational effects on
      the vocal tract of untrained subjects in singing phonation.
AB  - Magnetic Resonance Imaging (MRI) of subjects in a supine position can be used to
      evaluate the configuration of the vocal tract during phonation. However, studies
      of speech phonation have shown that gravity can affect vocal tract shape and bias
      measurements. This is one of the reasons that MRI studies of singing phonation
      have used professionally trained singers as subjects, because they are generally
      considered to be less affected by the supine body position and environmental
      distractions. A study of untrained singers might not only contribute to the
      understanding of intuitive singing function and aid the evaluation of potential
      hazards for vocal health, but also provide insights into the effect of the supine
      position on singers in general. In the present study, an open configuration 0.25
      T MRI system with a rotatable examination bed was used to study the effect of
      body position in 20 vocally untrained subjects. The subjects were asked to sing
      sustained tones in both supine and upright body positions on different pitches
      and in different register conditions. Morphometric measurements were taken from
      the acquired images of a sagittal slice depicting the vocal tract. The analysis
      concerning the vocal tract configuration in the two body positions revealed
      differences in 5 out of 10 measured articulatory parameters. In the upright
      position the jaw was less protruded, the uvula was elongated, the larynx more
      tilted and the tongue was positioned more to the front of the mouth than in the
      supine position. The findings presented are in agreement with several studies on
      gravitational effects in speech phonation, but contrast with the results of a
      previous study on professional singers of our group where only minor differences
      between upright and supine body posture were observed. The present study
      demonstrates that imaging of the vocal tract using weight-bearing MR imaging is a
      feasible tool for the study of sustained phonation in singing for vocally
      untrained subjects. 

PMID- 25379887
TI  - BiAg alloy nanospheres: a new photocatalyst for H2 evolution from water
      splitting.
AB  - We demonstrate for the first time that Bi and BiAg alloy nanospheres, fabricated
      with a facile hydrothermal method, display evident photocatalytic H2 production
      activities. Element Bi can serve as an active photocatalyst for both water
      splitting and photoelectrochemical applications. More interestingly, these
      activities of Bi can be greatly enhanced by introducing Ag to form BiAg alloy
      nanoparticles, which may be ascribed to the improved charge separation and
      enlarged carrier concentration. The constituent of the BiAg alloy can be
      rationally tuned by varying the amount of Ag nanowires, and it is found that
      Bi0.7Ag0.3 exhibits the highest photoelectrochemical property. 

PMID- 25379888
TI  - Commentary on: Increase in visceral fat per se does not induce insulin resistance
      in the canine model.

PMID- 25379889
TI  - Crystal structure of Bombyx mori lipoprotein 6: comparative structural analysis
      of the 30-kDa lipoprotein family.
AB  - The 30-kDa lipoprotein (LP) family of mulberry silkworm comprises major hemolymph
      proteins specific to the fifth instar larvae. The family consists of 46 members,
      24 of which are referred to as typical 30-kDa LPs. To date, two crystal
      structures of 30-kDa LPs from Bombyx mori have been described (Bmlp3 and Bmlp7).
      Here, we present the crystal structure of Bmlp6, another 30-kDa LP member. Bmlp6
      is comprised of two domains characteristic of this family, the VHS-type N
      terminal domain and beta-trefoil C-terminal domain. The structures of the three
      30-kDa LPs have been compared and a number of differences are noted, including
      loop conformation, the surface electrostatic potential, and the potential binding
      cavities. We discuss the observed structural differences in the light of the
      potential different roles of the particular 30-kDa LP members in silkworm
      physiology. 

PMID- 25379886
TI  - Identification of serum microRNA signatures for diagnosis of mild traumatic brain
      injury in a closed head injury model.
AB  - Wars in Iraq and Afghanistan have highlighted the problems of diagnosis and
      treatment of mild traumatic brain injury (mTBI). MTBI is a heterogeneous injury
      that may lead to the development of neurological and behavioral disorders. In the
      absence of specific diagnostic markers, mTBI is often unnoticed or misdiagnosed.
      In this study, mice were induced with increasing levels of mTBI and microRNA
      (miRNA) changes in the serum were determined. MTBI was induced by varying weight
      and fall height of the impactor rod resulting in four different severity grades
      of the mTBI. Injuries were characterized as mild by assessing with the
      neurobehavioral severity scale-revised (NSS-R) at day 1 post injury. Open field
      locomotion and acoustic startle response showed behavioral and sensory motor
      deficits in 3 of the 4 injury groups at day 1 post injury. All of the animals
      recovered after day 1 with no significant neurobehavioral alteration by day 30
      post injury. Serum microRNA (miRNA) profiles clearly differentiated injured from
      uninjured animals. Overall, the number of miRNAs that were significantly
      modulated in injured animals over the sham controls increased with the severity
      of the injury. Thirteen miRNAs were found to identify mTBI regardless of its
      severity within the mild spectrum of injury. Bioinformatics analyses revealed
      that the more severe brain injuries were associated with a greater number of
      miRNAs involved in brain related functions. The evaluation of serum miRNA may
      help to identify the severity of brain injury and the risk of developing adverse
      effects after TBI. 

PMID- 25379891
TI  - Na+,K+-ATPase activity is increased in rats subjected to chronic administration
      of ketamine.

PMID- 25379892
TI  - Bipolar disorder and adiposity: a study using whole body dual energy X-ray
      absorptiometry scans.

PMID- 25379890
TI  - Sensitive real-time PCR detection of pathogenic Leptospira spp. and a comparison
      of nucleic acid amplification methods for the diagnosis of leptospirosis.
AB  - BACKGROUND: Bacteria of the genus Leptospira, the causative agents of
      leptospirosis, are categorized into pathogenic and non-pathogenic species.
      However, the benefit of using a clinical diagnostic that is specific for
      pathogenic species remains unclear. In this study, we present the development of
      a real-time PCR (rtPCR) for the detection of pathogenic Leptospira (the
      pathogenic rtPCR), and we perform a comparison of the pathogenic rtPCR with a
      published assay that detects all Leptospira species [the undifferentiated febrile
      illness (UFI) assay] and a reference 16S Leptospira rtPCR, which was originally
      designed to detect pathogenic species. METHODOLOGY/PRINCIPAL FINDINGS: For the
      pathogenic rtPCR, a new hydrolysis probe was designed for use with primers from
      the UFI assay, which targets the 16S gene. The pathogenic rtPCR detected
      Leptospira DNA in 37/37 cultured isolates from 5 pathogenic and one intermediate
      species. Two strains of the non-pathogenic L. biflexa produced no signal.
      Clinical samples from 65 patients with suspected leptospirosis were then tested
      using the pathogenic rtPCR and a reference Leptospira 16S rtPCR. All 65 samples
      had tested positive for Leptospira using the UFI assay; 62 (95.4%) samples tested
      positive using the pathogenic rtPCR (p = 0.24). Only 24 (36.9%) samples tested
      positive in the reference 16S rtPCR (p<0.0001 for comparison with the pathogenic
      rtPCR and UFI assays). Amplicon sequencing confirmed the detection of pathogenic
      Leptospira species in 49/50 cases, including 3 cases that were only detected
      using the UFI assay. CONCLUSIONS/SIGNIFICANCE: The pathogenic rtPCR displayed
      similar sensitivity to the UFI assay when testing clinical specimens with no
      difference in specificity. Both assays proved significantly more sensitive than a
      real-time molecular test used for comparison. Future studies are needed to
      investigate the clinical and epidemiologic significance of more sensitive
      Leptospira detection using these tests.

PMID- 25379893
TI  - Association of social anxiety with stigmatisation and low self-esteem in remitted
      bipolar patients.

PMID- 25379894
TI  - Val66Met polymorphism and serum brain-derived neurotrophic factor concentration
      in depressed patients.

PMID- 25379895
TI  - Depression is associated with lower circulating endothelial progenitor cells and
      increased inflammatory markers.

PMID- 25379896
TI  - Administration of cannabidiol and imipramine induces antidepressant-like effects
      in the forced swimming test and increases brain-derived neurotrophic factor
      levels in the rat amygdala.

PMID- 25379898
TI  - Induced psychosis after withdrawal of varenicline: a case report.

PMID- 25379897
TI  - Foreign accent syndrome caused by a left temporal-parietal ischaemic stroke.
AB  - Karanasios P, Loukopoulou P, Zampakis P, Tiligadas T, Makridou A, Doukas V,
      Argyriou AA. Foreign accent syndrome caused by a left temporal-parietal ischaemic
      stroke. AIM: We present the first reported case of a Greek patient with foreign
      accent syndrome (FAS) secondary to a left temporal-parietal ischemic stroke. CASE
      REPORT: A 76 year-old right-handed, Greek in origin, male was referred because he
      had suddenly manifested changes in speech expression. The neurological
      examination revealed that his prior typical English-Australian accent resembled a
      mixture of Greek and English-Britain accent consistent with FAS, though he had
      visited only once Greece the last 15 years and never had been to United Kingdom.
      RESULTS: A brain Magnetic Resonance Imaging scan depicted an ischemic temporal
      lesion in the language-dominant left hemisphere, affecting the left posterior
      superior and middle temporal gyri, as well as the ipsilateral inferior
      supramarginal angular gyrus and posterior insula. CONCLUSION: We might suggest
      that FAS in our patient was induced because of interrupted cortical-subcortical
      feedback pathways. The phenomenon of subcortical-cortical diaschisis might also
      have contributed to its clinical manifestation.

PMID- 25379899
TI  - Automatic background knowledge selection for matching biomedical ontologies.
AB  - Ontology matching is a growing field of research that is of critical importance
      for the semantic web initiative. The use of background knowledge for ontology
      matching is often a key factor for success, particularly in complex and lexically
      rich domains such as the life sciences. However, in most ontology matching
      systems, the background knowledge sources are either predefined by the system or
      have to be provided by the user. In this paper, we present a novel methodology
      for automatically selecting background knowledge sources for any given ontologies
      to match. This methodology measures the usefulness of each background knowledge
      source by assessing the fraction of classes mapped through it over those mapped
      directly, which we call the mapping gain. We implemented this methodology in the
      AgreementMakerLight ontology matching framework, and evaluate it using the
      benchmark biomedical ontology matching tasks from the Ontology Alignment
      Evaluation Initiative (OAEI) 2013. In each matching problem, our methodology
      consistently identified the sources of background knowledge that led to the
      highest improvements over the baseline alignment (i.e., without background
      knowledge). Furthermore, our proposed mapping gain parameter is strongly
      correlated with the F-measure of the produced alignments, thus making it a good
      estimator for ontology matching techniques based on background knowledge. 

PMID- 25379902
TI  - Editorial: A marketplace for physics.

PMID- 25379901
TI  - Needles of Pinus halepensis as biomonitors of bioaerosol emissions.
AB  - We propose using the surface of pine trees needles to biomonitor the bioaerosol
      emissions at a composting plant. Measurements were based on 16S rRNA gene copy
      numbers of Saccharopolyspora rectivirgula, a bioindicator of composting plant
      emissions. A sampling plan was established based on 29 samples around the
      emission source. The abundance of 16S rRNA gene copies of S. rectivirgula per
      gram of Pinus halepensis needles varied from 104 to 102 as a function of the
      distance. The signal reached the background level at distances around the
      composting plant ranging from 2 km to more than 5.4 km, depending on the local
      topography and average wind directions. From these values, the impacted area
      around the source of bioaerosols was mapped. 

PMID- 25379903
TI  - Observable measure of quantum coherence in finite dimensional systems.
AB  - Quantum coherence is the key resource for quantum technology, with applications
      in quantum optics, information processing, metrology, and cryptography. Yet,
      there is no universally efficient method for quantifying coherence either in
      theoretical or in experimental practice. I introduce a framework for measuring
      quantum coherence in finite dimensional systems. I define a theoretical measure
      which satisfies the reliability criteria established in the context of quantum
      resource theories. Then, I present an experimental scheme implementable with
      current technology which evaluates the quantum coherence of an unknown state of a
      d-dimensional system by performing two programmable measurements on an ancillary
      qubit, in place of the O(d2) direct measurements required by full state
      reconstruction. The result yields a benchmark for monitoring quantum effects in
      complex systems, e.g., certifying nonclassicality in quantum protocols and
      probing the quantum behavior of biological complexes.

PMID- 25379904
TI  - Experimental detection of entanglement with optimal-witness families.
AB  - We report an experiment in which one determines, with least tomographic effort,
      whether an unknown two-photon polarization state is entangled or separable. The
      method measures whole families of optimal entanglement witnesses. We introduce
      adaptive measurement schemes that greatly speed up the entanglement detection.
      The experiments are performed on states of different ranks, and we find good
      agreement with results from computer simulations. 

PMID- 25379906
TI  - Experimental generation of continuous-variable hyperentanglement in an optical
      parametric oscillator.
AB  - We report on the generation of continuous-variable hyperentanglement of
      polarization and orbital angular momentum with a type II optical parametric
      oscillator. By compensating for the astigmatism between spatial modes, we produce
      an entangled pair of Hermite-Gauss beams. From correlations measurements, we
      verify the existence of continuous-variable hyperentanglement by the general
      entanglement criterion as well as by the continuous-variable version of the Peres
      Horodecki criterion visualized on an equivalent Poincare sphere. 

PMID- 25379905
TI  - Relaxation dynamics of a Fermi gas in an optical superlattice.
AB  - This Letter comprises an experimental and theoretical investigation of the time
      evolution of a Fermi gas following fast and slow quenches of a one-dimensional
      optical double-well superlattice potential. We investigate both the local
      tunneling in the connected double wells and the global dynamics towards a steady
      state, i.e., a time-independent state. The local observables in the steady state
      resemble those of a thermal equilibrium state, whereas the global properties
      indicate a strong nonequilibrium situation. 

PMID- 25379907
TI  - Fast thermalization and Helmholtz oscillations of an ultracold Bose gas.
AB  - We analyze theoretically the transport properties of a weakly interacting
      ultracold Bose gas enclosed in two reservoirs connected by a constriction. We
      assume that the transport of the superfluid part is hydrodynamic, and we describe
      the ballistic transport of the normal part using the Landauer-Buttiker formalism.
      Modeling the coupled evolution of the phase, atom number, and temperature
      mismatches between the reservoirs, we predict that Helmholtz (plasma)
      oscillations can be observed at nonzero temperatures below Tc. We show that,
      because of its strong compressibility, the Bose gas is characterized by a fast
      thermalization compared to the damping time for plasma oscillations, accompanied
      by a fast transfer of the normal component. This fast thermalization also affects
      the gas above Tc, where we present a comparison to the ideal fermionic case.
      Moreover, we outline the possible realization of a superleak through the
      inclusion of a disordered potential.

PMID- 25379908
TI  - Asymptotic freedom in Horava-Lifshitz gravity.
AB  - We use the Wetterich equation for foliated spacetimes to study the
      renormalization group flow of projectable Horava-Lifshitz gravity coupled to n
      Lifshitz scalars. Using novel results for anisotropic heat kernels, the matter
      induced beta functions for the gravitational couplings are computed explicitly.
      The renormalization group flow exhibits an UV attractive anisotropic Gaussian
      fixed point where Newton's constant vanishes and the extra scalar mode decouples.
      This fixed point ensures that the theory is asymptotically free in the large-n
      expansion, indicating that projectable Horava-Lifshitz gravity is perturbatively
      renormalizable. Notably, the fundamental fixed point action does not obey
      detailed balance. 

PMID- 25379909
TI  - Mechanism for thermal relic dark matter of strongly interacting massive
      particles.
AB  - We present a new paradigm for achieving thermal relic dark matter. The mechanism
      arises when a nearly secluded dark sector is thermalized with the standard model
      after reheating. The freeze-out process is a number-changing 3->2 annihilation of
      strongly interacting massive particles (SIMPs) in the dark sector, and points to
      sub-GeV dark matter. The couplings to the visible sector, necessary for
      maintaining thermal equilibrium with the standard model, imply measurable signals
      that will allow coverage of a significant part of the parameter space with future
      indirect- and direct-detection experiments and via direct production of dark
      matter at colliders. Moreover, 3->2 annihilations typically predict sizable 2->2
      self-interactions which naturally address the "core versus cusp" and "too-big-to
      fail" small-scale structure formation problems. 

PMID- 25379910
TI  - Scattering of massless particles in arbitrary dimensions.
AB  - We present a compact formula for the complete tree-level S-matrix of pure Yang
      Mills and gravity theories in arbitrary spacetime dimensions. The new formula for
      the scattering of n particles is given by an integral over the positions of n
      points on a sphere restricted to satisfy a dimension-independent set of
      equations. The integrand is constructed using the reduced Pfaffian of a 2n*2n
      matrix, Psi, that depends on momenta and polarization vectors. In its simplest
      form, the gravity integrand is a reduced determinant which is the square of the
      Pfaffian in the Yang-Mills integrand. Gauge invariance is completely manifest as
      it follows from a simple property of the Pfaffian. 

PMID- 25379913
TI  - Baryogenesis from strong CP violation and the QCD axion.
AB  - We show that strong CP violation from the QCD axion can be responsible for the
      matter antimatter asymmetry of the Universe in the context of cold electroweak
      baryogenesis if the electroweak phase transition is delayed below the GeV scale.
      This can occur naturally if the Higgs couples to a O(100)  GeV dilaton, as
      expected in some models where the Higgs is a pseudo-Nambu-Goldstone boson of a
      new strongly interacting sector at the TeV scale. The existence of such a second
      scalar resonance with a mass and properties similar to the Higgs boson will soon
      be tested at the LHC. In this context, the QCD axion would not only solve the
      strong CP problem, but also the matter antimatter asymmetry and dark matter. 

PMID- 25379912
TI  - Strong constraints on sub-GeV dark sectors from SLAC beam dump E137.
AB  - We present new constraints on sub-GeV dark matter and dark photons from the
      electron beam-dump experiment E137 conducted at SLAC in 1980-1982. Dark matter
      interacting with electrons (e.g., via a dark photon) could have been produced in
      the electron-target collisions and scattered off electrons in the E137 detector,
      producing the striking, zero-background signature of a high-energy
      electromagnetic shower that points back to the beam dump. E137 probes new and
      significant ranges of parameter space and constrains the well-motivated
      possibility that dark photons that decay to light dark-sector particles can
      explain the ~3.6sigma discrepancy between the measured and standard model value
      of the muon anomalous magnetic moment. It also restricts the parameter space in
      which the relic density of dark matter in these models is obtained from thermal
      freeze-out. E137 also convincingly demonstrates that (cosmic) backgrounds can be
      controlled and thus serves as a powerful proof of principle for future beam-dump
      searches for sub-GeV dark-sector particles scattering off electrons in the
      detector. 

PMID- 25379915
TI  - QCD sum rules for magnetically induced mixing between etac and J/psi.
AB  - We investigate the properties of charmonia in strong magnetic fields by using QCD
      sum rules. We show how to implement the mixing effects between eta(c) and J/psi
      on the basis of field-theoretical approaches, and then show that the sum rules
      are saturated by the mixing effects with phenomenologically determined
      parameters. Consequently, we find that the mixing effects are the dominant
      contribution to the mass shifts of the static charmonia in strong magnetic
      fields.

PMID- 25379916
TI  - Nonlinear interaction between single photons.
AB  - Harnessing nonlinearities strong enough to allow single photons to interact with
      one another is not only a fascinating challenge but also central to numerous
      advanced applications in quantum information science. Here we report the
      nonlinear interaction between two single photons. Each photon is generated in
      independent parametric down-conversion sources. They are subsequently combined in
      a nonlinear waveguide where they are converted into a single photon of higher
      energy by the process of sum-frequency generation. Our approach results in the
      direct generation of photon triplets. More generally, it highlights the potential
      for quantum nonlinear optics with integrated devices and, as the photons are at
      telecom wavelengths, it opens the way towards novel applications in quantum
      communication such as device-independent quantum key distribution. 

PMID- 25379917
TI  - Full transmission and reflection of waves propagating through a maze of disorder.
AB  - Thirty years ago, theorists showed that a properly designed combination of
      incident waves could be fully transmitted through (or reflected by) a disordered
      medium, based on the existence of propagation channels which are essentially
      either closed or open (bimodal law). In this Letter, we study elastic waves in a
      disordered waveguide and present direct experimental evidence of the bimodal law.
      Full transmission and reflection are achieved. The wave field is monitored by
      laser interferometry and highlights the interference effects that take place
      within the scattering medium. 

PMID- 25379918
TI  - Classical dynamical localization.
AB  - We consider classical models of the kicked rotor type, with piecewise linear
      kicking potentials designed so that momentum changes only by multiples of a given
      constant. Their dynamics display quasilocalization of momentum, or quadratic
      growth of energy, depending on the arithmetic nature of the constant. Such purely
      classical features mimic paradigmatic features of the quantum kicked rotor,
      notably dynamical localization in momentum, or quantum resonances. We present a
      heuristic explanation, based on a classical phase space generalization of a well
      known argument, that maps the quantum kicked rotor on a tight-binding model with
      disorder. Such results suggest reconsideration of generally accepted views that
      dynamical localization and quantum resonances are a pure result of quantum
      coherence. 

PMID- 25379921
TI  - Phonon localization by mass disorder in dense hydrogen-deuterium binary alloy.
AB  - Using a combination of the Raman spectroscopy and density functional theory
      calculations on dense hydrogen-deuterium mixtures of various concentrations, we
      demonstrate that, at 300 K and above 200 GPa, they transform into phase IV,
      forming a disordered binary alloy with six highly localized intramolecular
      vibrational (vibrons) and four delocalized low-frequency (<1200  cm(-1)) modes.
      Hydrogen-deuterium mixtures are unique in showing a purely mass-induced
      localization effect in the quantum solid: chemical bonding is isotope-independent
      while the mass varies by a factor of 2.

PMID- 25379920
TI  - Plasma-resistivity-induced strong damping of the kinetic resistive wall mode.
AB  - An energy-principle-based dispersion relation is derived for the resistive wall
      mode, which incorporates both the drift kinetic resonance between the mode and
      energetic particles and the resistive layer physics. The equivalence between the
      energy-principle approach and the resistive layer matching approach is first
      demonstrated for the resistive plasma resistive wall mode. As a key new result,
      it is found that the resistive wall mode, coupled to the favorable average
      curvature stabilization inside the resistive layer (as well as the toroidal
      plasma flow), can be substantially more stable than that predicted by drift
      kinetic theory with fast ion stabilization, but with the ideal fluid assumption.
      Since the layer stabilization becomes stronger with decreasing plasma
      resistivity, this regime is favorable for reactor scale, high-temperature fusion
      devices. 

PMID- 25379919
TI  - Grueneisen relaxation photoacoustic microscopy.
AB  - The temperature-dependent property of the Grueneisen parameter has been employed
      in photoacoustic imaging mainly to measure tissue temperature. Here we explore
      this property using a different approach and develop Grueneisen relaxation
      photoacoustic microscopy (GR-PAM), a technique that images nonradiative
      absorption with confocal optical resolution. GR-PAM sequentially delivers two
      identical laser pulses with a microsecond-scale time delay. The first laser pulse
      generates a photoacoustic signal and thermally tags the in-focus absorbers. When
      the second laser pulse excites the tagged absorbers within the thermal relaxation
      time, a photoacoustic signal stronger than the first one is produced, owing to
      the temperature dependence of the Grueneisen parameter. GR-PAM detects the
      amplitude difference between the two colocated photoacoustic signals, confocally
      imaging the nonradiative absorption. We greatly improved axial resolution from 45
      MUm to 2.3  MUm and, at the same time, slightly improved lateral resolution from
      0.63  MUm to 0.41  MUm. In addition, the optical sectioning capability
      facilitates the measurement of the absolute absorption coefficient without
      fluence calibration.

PMID- 25379922
TI  - Stability, energetics, and magnetic states of cobalt adatoms on graphene.
AB  - We investigate the stability and electronic properties of single Co atoms on
      graphene with near-exact many-body calculations. A frozen-orbital embedding
      scheme was combined with auxiliary-field quantum Monte Carlo calculations to
      increase the reach in system sizes. Several energy minima are found as a function
      of the distance h between Co and graphene. Energetics only permit the Co atom to
      occupy the top site at h=2.2  A in a high-spin 3d(8)4s(1) state, and the van der
      Waals region at h=3.3  A in a high-spin 3d(7)4s(2) state. The findings provide an
      explanation for recent experimental results with Co on free-standing graphene.

PMID- 25379923
TI  - Programmable mechanical metamaterials.
AB  - We create mechanical metamaterials whose response to uniaxial compression can be
      programmed by lateral confinement, allowing monotonic, nonmonotonic, and
      hysteretic behavior. These functionalities arise from a broken rotational
      symmetry which causes highly nonlinear coupling of deformations along the two
      primary axes of these metamaterials. We introduce a soft mechanism model which
      captures the programmable mechanics, and outline a general design strategy for
      confined mechanical metamaterials. Finally, we show how inhomogeneous confinement
      can be explored to create multistability and giant hysteresis. 

PMID- 25379924
TI  - Unexpected reconstruction of the alpha-boron (111) surface.
AB  - We report a novel reconstruction of the alpha-boron (111) surface, discovered
      using ab initio evolutionary structure prediction, and show that this unexpected
      neat structure has a much lower energy than the recently proposed (111)-I(R,(a))
      surface. In this reconstruction, all single interstitial boron atoms bridge
      neighboring B(12) icosahedra by polar covalent bonds, and this satisfies the
      electron counting rule, leading to the reconstruction-induced metal-semiconductor
      transition. The peculiar charge transfer between the interstitial atoms and the
      icosahedra plays an important role in stabilizing the surface.

PMID- 25379925
TI  - Phonon-assisted crossover from a nonmagnetic Peierls insulator to a magnetic
      Stoner metal.
AB  - We report a unique temperature-induced insulator-metal transition in MnB4 that is
      accompanied by a simultaneous magnetostructural change from a nonmagnetic
      monoclinic mP20 phase to a magnetic orthorhombic oP10 phase. Such a concurring
      magnetostructural and insulator-metal transformation is a manifestation of a
      strong competition between Peierls and Stoner mechanisms that governs a crossover
      from an electron-pairing to an electron-localization scenario in this system.
      Therefore, the phase stability of MnB4 is controlled by a subtle interplay among
      the Peierls mechanism, Stoner mechanism, and phonon free energy. Our findings not
      only resolve the longstanding magnetostructural puzzle of MnB4 but also provide a
      realistic system for the Peierls-Hubbard model.

PMID- 25379926
TI  - Quantum phases of the Shastry-Sutherland Kondo lattice: implications for the
      global phase diagram of heavy-fermion metals.
AB  - Considerable recent theoretical and experimental effort has been devoted to the
      study of quantum criticality and novel phases of antiferromagnetic heavy-fermion
      metals. In particular, quantum phase transitions have been discovered in heavy
      fermion compounds with geometrical frustration. These developments have motivated
      us to study the competition between the Ruderman-Kittel-Kasuya-Yosida and Kondo
      interactions on the Shastry-Sutherland lattice. We determine the zero-temperature
      phase diagram as a function of magnetic frustration and Kondo coupling within a
      slave-fermion approach. Pertinent phases include the valence bond solid and heavy
      Fermi liquid. In the presence of antiferromagnetic order, our zero-temperature
      phase diagram is remarkably similar to the global phase diagram proposed earlier
      based on general grounds. We discuss the implications of our results for the
      experiments on Yb2Pt2Pb and related compounds.

PMID- 25379927
TI  - Damping of confined modes in a ferromagnetic thin insulating film: angular
      momentum transfer across a nanoscale field-defined interface.
AB  - We observe a dependence of the damping of a confined mode of precessing
      ferromagnetic magnetization on the size of the mode. The micron-scale mode is
      created within an extended, unpatterned yttrium iron garnet film by means of the
      intense local dipolar field of a micromagnetic tip. We find that the damping of
      the confined mode scales like the surface-to-volume ratio of the mode, indicating
      an interfacial damping effect (similar to spin pumping) due to the transfer of
      angular momentum from the confined mode to the spin sink of ferromagnetic
      material in the surrounding film. Though unexpected for insulating systems, the
      measured intralayer spin-mixing conductance g_??=5.3*10(19)  m(-2) demonstrates
      efficient intralayer angular momentum transfer.

PMID- 25379928
TI  - Hybrid spin and valley quantum computing with singlet-triplet qubits.
AB  - The valley degree of freedom in the electronic band structure of silicon,
      graphene, and other materials is often considered to be an obstacle for quantum
      computing (QC) based on electron spins in quantum dots. Here we show that control
      over the valley state opens new possibilities for quantum information processing.
      Combining qubits encoded in the singlet-triplet subspace of spin and valley
      states allows for universal QC using a universal two-qubit gate directly provided
      by the exchange interaction. We show how spin and valley qubits can be separated
      in order to allow for single-qubit rotations. 

PMID- 25379929
TI  - First-principles approach to calculating energy level alignment at aqueous
      semiconductor interfaces.
AB  - A first-principles approach is demonstrated for calculating the relationship
      between an aqueous semiconductor interface structure and energy level alignment.
      The physical interface structure is sampled using density functional theory based
      molecular dynamics, yielding the interface electrostatic dipole. The  GW approach
      from many-body perturbation theory is used to place the electronic band edge
      energies of the semiconductor relative to the occupied 1b1 energy level in water.
      The application to the specific cases of nonpolar (101-0) facets of GaN and ZnO
      reveals a significant role for the structural motifs at the interface, including
      the degree of interface water dissociation and the dynamical fluctuations in the
      interface Zn-O and O-H bond orientations. These effects contribute up to 0.5 eV.

PMID- 25379930
TI  - Theoretical prediction of a time-reversal broken chiral superconducting phase
      driven by electronic correlations in a single TiSe2 layer.
AB  - Bulk TiSe2 is an intrinsically layered transition metal dichalcogenide hosting
      both superconducting and charge-density-wave ordering. Motivated by the recent
      progress in preparing two-dimensional transition metal dichalcogenides, we study
      these frustrated orderings in a single trilayer of TiSe2. Using a renormalization
      group approach, we find that electronic correlations can give rise to charge
      density-wave order and two kinds of superconductivity. One possible
      superconducting state corresponds to unconventional s(+-) pairing. The other is
      particularly exciting as it is chiral, breaking time-reversal symmetry. Its
      stability depends on the precise strength and screening of the electron-electron
      interactions in two-dimensional TiSe2.

PMID- 25379932
TI  - Odd-parity triplet superconducting phase in multiorbital materials with a strong
      spin-orbit coupling: application to doped Sr2IrO4.
AB  - We explore possible superconducting states in t(2g) multiorbital correlated
      electron systems with strong spin-orbit coupling (SOC). In order to study such
      systems in a controlled manner, we employ large-scale dynamical mean-field theory
      (DMFT) simulations with the hybridization expansion continuous-time quantum Monte
      Carlo (CTQMC) impurity solver. To determine the pairing symmetry, we go beyond
      the local DMFT formalism using parquet equations to introduce the momentum
      dependence in the two-particle vertex and correlation functions. In the strong
      SOC limit, a singlet, d-wave pairing state in the electron-doped side of the
      phase diagram is observed at weak Hund's coupling, which is triggered by
      antiferromagnetic fluctuations. When the Hund's coupling is comparable to SOC, a
      twofold degenerate, triplet p-wave pairing state with relatively high transition
      temperature emerges in the hole-doped side of the phase diagram, which is
      associated with enhanced charge fluctuations. Experimental implications to doped
      Sr2IrO4 are discussed.

PMID- 25379931
TI  - Neutron-scattering evidence for a periodically modulated superconducting phase in
      the underdoped cuprate La1.905Ba0.095CuO4.
AB  - The role of antiferromagnetic spin correlations in high-temperature
      superconductors remains a matter of debate. We present inelastic neutron
      scattering evidence that gapless spin fluctuations coexist with superconductivity
      in La1.905Ba0.095CuO4. Furthermore, we observe that both the low-energy magnetic
      spectral weight and the spin incommensurability are enhanced with the onset of
      superconducting correlations. We propose that the coexistence occurs through
      intertwining of spatial modulations of the pair wave function and the
      antiferromagnetic correlations. This proposal is also directly relevant to
      sufficiently underdoped La(2-x)Sr(x)CuO(4) and YBa(2)Cu(3)O(6+x).

PMID- 25379933
TI  - Disorder driven metal-insulator transition in BaPb(1-x)Bi(x)O3 and inference of
      disorder-free critical temperature.
AB  - We performed point-contact spectroscopy tunneling measurements on single crystal
      BaPb(1-x)Bi(x)O(3) for 0<=x<=0.28 at temperatures T=2-40  K and find a
      suppression in the density of states at low bias voltages that is characteristic
      of disordered metals. Both the correlation gap and the zero-temperature
      conductivity are zero at a critical concentration x(c)=0.30. Not only does this
      suggests that a disorder driven metal-insulator transition occurs before the
      onset of the charge disproportionated charge density wave insulator, but we also
      explore whether a scaling theory is applicable. In addition, we estimate the
      disorder-free critical temperature and compare these results to Ba(1
      x)K(x)BiO(3).

PMID- 25379934
TI  - In-plane magnetoresistance obeys Kohler's rule in the pseudogap phase of cuprate
      superconductors.
AB  - We report in-plane resistivity (rho) and transverse magnetoresistance (MR)
      measurements for underdoped HgBa(2)CuO(4+delta) (Hg1201). Contrary to the long
      standing view that Kohler's rule is strongly violated in underdoped cuprates, we
      find that it is in fact satisfied in the pseudogap phase of Hg1201. The
      transverse MR shows a quadratic field dependence, deltarho/rho(0)=aH(2), with
      a(T)?T(-4). In combination with the observed rho?T(2) dependence, this is
      consistent with a single Fermi-liquid quasiparticle scattering rate. We show that
      this behavior is typically masked in cuprates with lower structural symmetry or
      strong disorder effects.

PMID- 25379935
TI  - Tailoring the magnetism of Co atoms on graphene through substrate hybridization.
AB  - We determine the magnetic properties of individual Co atoms adsorbed on graphene
      (G) with x-ray absorption spectroscopy and magnetic circular dichroism. The
      magnetic ground state of Co adatoms strongly depends on the choice of the metal
      substrate on which graphene is grown. Cobalt atoms on G/Ru(0001) feature
      exceptionally large orbital and spin moments, as well as an out-of-plane easy
      axis with large magnetic anisotropy. Conversely, the magnetic moments are
      strongly reduced for Co/G/Ir(111), and the magnetization is of the easy-plane
      type. We demonstrate how the Co magnetic properties, which ultimately depend on
      the degree of hybridization between the Co 3d orbitals and graphene pi bands, can
      be tailored through the strength of the graphene-substrate coupling. 

PMID- 25379936
TI  - Detection of up-converted persistent luminescence in the near infrared emitted by
      the Zn3Ga2GeO8:Cr3+, Yb3+, Er3+ phosphor.
AB  - Up-conversion luminescence and long-persistent luminescence are two well-studied,
      special luminescence processes. By combining the unique features of these two
      luminescence processes, here we design a new luminescence process called up
      converted persistent luminescence (UCPL), which enables us to generate persistent
      luminescence having an emission energy higher than the excitation energy. Guided
      by the UCPL concept, we create the first UCPL phosphor Zn3Ga2GeO8:1%Cr3+, 5%Yb3+,
      0.5%Er3+ by incorporating an up-converting ion pair Yb3+/Er3+ into a
      Zn3Ga2GeO8:1%Cr3+ near-infrared persistent phosphor. After being excited by a 980
      nm laser, the phosphor emits long-lasting (>24  h) near-infrared persistent
      emission peaking at 700 nm. The UCPL concept and the associated phosphors are
      expected to have important implications for several fields such as biomedical
      imaging.

PMID- 25379937
TI  - Control of a two-dimensional electron gas on SrTiO3(111) by atomic oxygen.
AB  - We report on the formation of a two-dimensional electron gas (2DEG) at the bare
      surface of (111) oriented SrTiO3. Angle resolved photoemission experiments reveal
      highly itinerant carriers with a sixfold symmetric Fermi surface and strongly
      anisotropic effective masses. The electronic structure of the 2DEG is in good
      agreement with self-consistent tight-binding supercell calculations that
      incorporate a confinement potential due to surface band bending. We further
      demonstrate that alternate exposure of the surface to ultraviolet light and
      atomic oxygen allows tuning of the carrier density and the complete suppression
      of the 2DEG.

PMID- 25379938
TI  - Continuum modeling of secondary rheology in dense granular materials.
AB  - Recent dense granular flow experiments have shown that shear deformation in one
      region of a granular medium fluidizes its entirety, including regions far from
      the sheared zone, effectively erasing the yield condition everywhere. This
      enables slow creep deformation to occur when an external force is applied to a
      probe in the nominally static regions of the material. The apparent change in
      rheology induced by far-away motion is termed the "secondary rheology," and a
      theoretical rationalization of this phenomenon is needed. Recently, a new
      nonlocal granular rheology was successfully used to predict steady granular flow
      fields, including grain-size-dependent shear-band widths in a wide variety of
      flow configurations. We show that the nonlocal fluidity model is also capable of
      capturing secondary rheology. Specifically, we explore creep of a circular
      intruder in a two-dimensional annular Couette cell and show that the model
      captures all salient features observed in experiments, including both the rate
      independent nature of creep for sufficiently slow driving rates and the faster
      than-linear increase in the creep speed with the force applied to the intruder. 

PMID- 25379939
TI  - Artificial tribotactic microscopic walkers: walking based on friction gradients.
AB  - Friction, the resistive force between two surfaces sliding past each other, is at
      the core of a wide diversity of locomotion schemes. While such schemes are well
      described for homogeneous environments, locomotion based on friction in
      inhomogeneous environments has not received much attention. Here we introduce and
      demonstrate the concept of tribotaxis, a motion that is guided by gradients in
      the friction coefficient. Our system is composed of microwalkers that undergo an
      effective frictional interaction with biological receptors on the substrate,
      which is regulated by the density of such receptors. When actuated
      stochastically, microwalkers migrate to regions of higher friction, much like a
      chemotactic cell migrates to regions of higher chemoattractant concentration.
      Simulations and theory based on biased random walks are in excellent agreement
      with experiments. We foresee important implications for tribotaxis in artificial
      and natural locomotion in biological environments. 

PMID- 25379940
TI  - Gravity driven instability in elastic solid layers.
AB  - We demonstrate the instability of the free surface of a soft elastic solid facing
      downwards. Experiments are carried out using a gel of constant density rho, shear
      modulus MU, put in a rigid cylindrical dish of depth h. When turned upside down,
      the free surface of the gel undergoes a normal outgoing acceleration g. It
      remains perfectly flat for rhogh/MU<alpha* with alpha*?6, whereas a steady
      pattern spontaneously appears in the opposite case. This phenomenon results from
      the interplay between the gravitational energy and the elastic energy of
      deformation, which reduces the Rayleigh waves celerity and vanishes it at the
      threshold.

PMID- 25379941
TI  - Comment on "Formation of phase space holes and clumps".

PMID- 25379942
TI  - Lilley and Nyqvist reply.

PMID- 25379943
TI  - Comparative proteomics analysis of gastric cancer stem cells.
AB  - Cancer stem cells (CSCs) are responsible for cancer progression, metastasis, and
      recurrence. To date, the specific markers of CSCs remain undiscovered. The aim of
      this study was to identify novel biomarkers of gastric CSCs for clinical
      diagnosis using proteomics technology. CSC-like SP cells, OCUM-12/SP cells, OCUM
      2MD3/SP cells, and their parent OCUM-12 cells and OCUM-2MD3 cells were used in
      this study. Protein lysates from each cell line were analyzed using QSTAR Elite
      Liquid Chromatography with Tandem Mass Spectrometry, coupled with isobaric tags
      for relative and absolute quantitation technology. Candidate proteins detected by
      proteomics technology were validated by immunohistochemical analysis of 300
      gastric cancers. Based on the results of LC-MS/MS, eight proteins, including
      RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4, ALDOA, and KRT18, were up-regulated in
      both OCUM-12/SP cells and OCUM-2MD3/SP cells when compared to their corresponding
      parent cells. RT-PCR analysis indicated that the expression level of RBBP6,
      HSPA4, DCTPP1, HSPA9, VPS13A, ALDOA, GLG1, and CK18 was high in OCUM-12/SP and
      OCUM-2MD3/SP, in compared with the control of parent OCUM-12 and OCUM-2MD3. These
      proteins were significantly associated with advanced invasion depth, lymph node
      metastasis, distant metastasis, or advanced clinical stage. RBBP6, DCTPP1, HSPA4,
      and ALDOA expression in particular were significantly associated with a poor
      prognosis in the 300 gastric cancer patients. RBBP6 was determined to be an
      independent prognostic factor. The motility-stimulating ability of OCUM-12/SP
      cells and OCUM-2MD3/SP cells was inhibited by RBBP6 siRNA. These findings might
      suggest that the eight proteins, RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4,
      ALDOA, and KRT18, utilizing comparative proteomics analysis, were perceived to be
      potential CSC markers of gastric cancer. Of the eight candidate proteins, RBBP6
      was suggested to be a promising prognostic biomarker and a therapeutic target for
      gastric cancer. 

PMID- 25379945
TI  - Pyrazolylamidino ligands from coupling of acetonitrile and pyrazoles: a
      systematic study.
AB  - Mixed pyrazole-acetonitrile complexes, both neutral fac-[ReBr(CO)3(NCMe)(pz*H)]
      (pz*H = pzH, pyrazole; dmpzH, 3,5-dimethylpyrazole; or indzH, indazole) and
      cationic fac-[Re(CO)3(NCMe)(pz*H)2]A (A = BF4, ClO4, or OTf), are described.
      Their role as the only starting products to obtain final pyrazolylamidino
      complexes fac-[ReBr(CO)3(NH?C(Me)pz*-kappa(2)N,N)] and fac
      [Re(CO)3(pz*H)(NH?C(Me)pz*-kappa(2)N,N)]A, respectively, is examined. Other
      products involved in the processes, such as fac-[ReBr(CO)3(pz*H)2], fac
      [Re(CO)3(NCMe)(NH?C(Me)pz*-kappa(2)N,N)]A, and fac-[Re(CO)3(pz*H)2(OTf)] are also
      described. Warming CD3CN solutions of fac-[Re(CO)3(NCMe)(pz*H)2]A at 40  degrees
      C gives cleanly the pyrazolylamidino complexes [Re(CO)3(pz*H)(NH?C(Me)pz*
      kappa(2)N,N)]A as the only products, pointing to an intramolecular process. This
      is confirmed by carrying out reactions in the presence of one equivalent of a
      pyrazole different from that coordinated, which affords complexes where the
      pyrazolylamidino ligand contains only the pyrazole previously coordinated. When
      the reactions lead to an equilibrium mixture of the final and starting products,
      the reverse reaction gives the same equilibrium mixture, which indicates that the
      coupling reaction of pyrazoles and nitriles to obtain pyrazolylamidino ligands is
      a reversible intramolecular process. A systematic study of the possible factors
      which may affect the reaction gives the following results: (a) the yields of the
      direct reactions are higher for lower temperatures; (b) the tendency of the
      pyrazoles to give pyrazolylamidino complexes follows the sequence indzH > pzH >
      dmpzH; and (c) the reaction rates do not depend on the nature of the anion even
      when a large excess is added. The presence of a small amount of aqueous solution
      of NaOH catalyzes the reaction. Thus, addition of 0.5-1% of NaOH (aq) to
      solutions of fac-[ReBr(CO)3(NCMe)(pz*H)] (in CD3CN) or fac
      [Re(CO)3(NCMe)(pz*H)2]A (in CD3CN, CD3NO2 or (CD3)2CO) allowed the syntheses of
      the corresponding pyrazolylamidino complexes [ReBr(CO)3(NH?C(Me)pz*-kappa(2)N,N)]
      or [Re(CO)3(pz*H)(NH?C(Me)pz*-kappa(2)N,N)]A with better yields, more rapidly,
      and in milder conditions. 

PMID- 25379944
TI  - Correlation between Surgeon's experience, surgery complexity and the alteration
      of stress related physiological parameters.
AB  - INTRODUCTION: In the present work we analyzed the hormonal (salivary Cortisol;
      sC), immune (salivary Immunoglobulin A; sIgA) and cardiovascular (Heart rate, HR,
      and systolic blood pressure, SBP) responses induced by stress conditions in oral
      surgeons, randomly recruited according to their expertise level. MATERIALS AND
      METHODS: Each surgeon performed three different surgical procedures with
      increasing degrees of technical difficulty and under time-limited conditions, to
      assess whether these variants may influence the risks of stress-induced secondary
      hypertension among the involved health professionals. sC and sIgA samples and
      cardiovascular function measurements were taken up before, during, and two hours
      after every surgery. Salivary samples and cardiovascular measurements were taken
      also during non-surgical days, as baseline controls. RESULTS: We observed that
      more experienced surgeons showed a higher stress management ability compared to
      those with less experience or, generally, younger, which are more exposed to the
      risks of developing secondary hypertension. Nevertheless, indipendently of sex
      and experience, oral surgeons are constantly exposed to high risks of developing
      stress-related diseases. CONCLUSIONS: On the basis of the issues addressed and
      the results obtained, we have highlighted the importance of the investigated
      stress biomarkers to monitor and to prevent stress-related pathologies among oral
      surgeons. This approach is aimed to emphasize the significance of these specific
      stress-biomarkers, which represent a powerful instrument to evaluate stress
      levels in oral surgeons, and that may help to reduce the most severe life
      threatening risks to which they are daily exposed. In conclusion, final goal of
      this study is to suggest an useful guideline to monitor the stress levels of oral
      and maxillofacial surgeons in order to improve their quality of life, which is
      inevitably reflected on the quality of the performances provided and, finally, to
      prevent possible mistakes in their daily activities.

PMID- 25379946
TI  - MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible
      mechanism.
AB  - AIMS: Mechanisms regulating adiponectin expression have not been fully clarified.
      MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are
      involved in biological processes, including obesity and insulin resistance. We
      evaluated whether the miRNA-378 pathway is involved in regulating adiponectin
      expression. METHODS AND RESULTS: First, we determined a putative target site for
      miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by
      in silico analysis. The levels of adiponectin mRNA and protein were decreased in
      3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in
      HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was
      inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed
      by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory
      effects of the mimic were cancelled in a deleted mutant of the miR-378 3'-UTR
      binding site. Addition of tumor necrosis factor-alpha (TNFalpha) led a
      upregulation of miR-378 and downregulation of adiponectin at mRNA and protein
      levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin
      was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of
      miR378 and adiponectin were negatively well correlated (r = -0.624, p = 0.004).
      CONCLUSIONS: We found that levels of miRNA-378 could modulate adiponectin
      expression via the 3'UTR sequence-binding site. Our findings warrant further
      investigations into the role of miRNAs in regulating the adiponectin expression.

PMID- 25379947
TI  - Assessment of Short-Term Changes in Optic Nerve Head Hemodynamics in Hyperoxic
      Conditions with Laser Speckle Flowgraphy.
AB  - PURPOSE: To evaluate laser speckle flowgraphy (LSFG) measurements of the optic
      nerve head (ONH) blood flow (BF) response to hyperoxia. METHODS: This prospective
      study included 30 eyes of 30 healthy volunteers (mean age: 28.5 +/- 4.0,
      male:female = 13:17). The testing protocol had three phases: in the baseline
      phase, subjects breathed room air; in the hyperoxic phase, they breathed pure
      oxygen (6 L/min) for 15 min; and in the recovery phase, they were room air for 15
      min. LSFG measurements of mean blur rate (MBR), which represents ONH BF, were
      taken every minute. The MBR ratio in the hyperoxic and recovery phases was
      calculated with reference to this baseline. Clinical parameters, including
      systemic blood pressure, pulse rate, and saturation of pulse-oximetry oxygen
      (SpO2), were measured every 5 min. RESULTS: SpO2 increased significantly during
      hyperoxia (97.3 +/- 1.1% to 99.3 +/- 0.7%, p < 0.001). While clinical parameters
      were similar in hyperoxia and baseline, MBR decreased significantly after 2 min
      of hyperoxia (90.8 +/- 12.6%, p = 0.02), stayed steady throughout hyperoxia
      (mean: 89.5 +/- 10.8%, p range: <0.001-0.04) compared with baseline, and returned
      to baseline 1 min after recovery (93.7 +/- 10.3%, p = 0.25). A linear regression
      using a third-order polynomial fitting curve analysis revealed that the time to
      reach minimum MBR was 7.78 min (adjusted R(2 )= 0.87). CONCLUSION: LSFG could
      effectively assess ONH BF changes during hyperoxia.

PMID- 25379948
TI  - Paradoxical responses of plasma glucagon and bile acid levels after duodenal
      nutrient exclusion.

PMID- 25379914
TI  - Measurement of the B-s0 meson lifetime in Ds+pi- decays.
AB  - We present a measurement of the ratio of the B-s0 meson lifetime, in the flavor
      specific decay to Ds+pi-, to that of the B-0 meson. The pp collision data used
      correspond to an integrated luminosity of 1  fb(-1), collected with the LHCb
      detector, at a center-of-mass energy of 7 TeV. Combining our measured value of
      1.010+/-0.010+/-0.008 for this ratio with the known B-0 lifetime, we determine
      the flavor-specific B-s0 lifetime to be tau(B-s0 )=1.535+/-0.015+/-0.014  ps,
      where the uncertainties are statistical and systematic, respectively. This is the
      most precise measurement to date, and is consistent with previous measurements
      and theoretical predictions.

PMID- 25379949
TI  - Caspase-8 controls the gut response to microbial challenges by Tnf-alpha
      dependent and independent pathways.
AB  - OBJECTIVES: Intestinal epithelial cells (IEC) express toll-like receptors (TLR)
      that facilitate microbial recognition. Stimulation of TLR ligands induces a
      transient increase in epithelial cell shedding, a mechanism that serves the
      antibacterial and antiviral host defence of the epithelium and promotes
      elimination of intracellular pathogens. Although activation of the extrinsic
      apoptosis pathway has been described during inflammatory shedding, its functional
      involvement is currently unclear. DESIGN: We investigated the functional
      involvement of caspase-8 signalling in microbial-induced intestinal cell shedding
      by injecting Lipopolysaccharide (LPS) to mimic bacterial pathogens and poly(I:C)
      as a probe for RNA viruses in vivo. RESULTS: TLR stimulation of IEC was
      associated with a rapid activation of caspase-8 and increased epithelial cell
      shedding. In mice with an epithelial cell-specific deletion of caspase-8 TLR
      stimulation caused Rip3-dependent epithelial necroptosis instead of apoptosis.
      Mortality and tissue damage were more severe in mice in which IECs died by
      necroptosis than apoptosis. Inhibition of receptor-interacting protein (Rip)
      kinases rescued the epithelium from TLR-induced gut damage. TLR3-induced
      necroptosis was directly mediated via TRIF-dependent pathways, independent of Tnf
      alpha and type III interferons, whereas TLR4-induced tissue damage was critically
      dependent on Tnf-alpha. CONCLUSIONS: Together, our data demonstrate an essential
      role for caspase-8 in maintaining the gut barrier in response to mucosal
      pathogens by permitting inflammatory shedding and preventing necroptosis of
      infected cells. These data suggest that therapeutic strategies targeting the cell
      death machinery represent a promising new option for the treatment of
      inflammatory and infective enteropathies.

PMID- 25379950
TI  - Demonstration of the usefulness of epigenetic cancer risk prediction by a
      multicentre prospective cohort study.
AB  - BACKGROUND: Epigenetic alterations accumulate in normal-appearing tissues of
      patients with cancer, producing an epigenetic field defect. Cross-sectional
      studies show that the degree of the defect may be associated with risk in some
      types of cancer, especially cancers associated with chronic inflammation.
      OBJECTIVE: To demonstrate, by a multicentre prospective cohort study, that the
      risk of metachronous gastric cancer after endoscopic resection (ER) can be
      predicted by assessment of the epigenetic field defect using methylation levels.
      DESIGN: Patients with early gastric cancer, aged 40-80 years, who planned to
      have, or had undergone, ER, were enrolled at least 6 months after Helicobacter
      pylori infection discontinued. Methylation levels of three preselected genes (miR
      124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR.
      Patients were followed up annually by endoscopy, and the primary endpoint was
      defined as detection of a metachronous gastric cancer. Authentic metachronous
      gastric cancers were defined as cancers excluding those detected within 1 year
      after the enrolment. RESULTS: Among 826 patients enrolled, 782 patients had at
      least one follow-up, with a median follow-up of 2.97 years. Authentic
      metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at
      1-2, 2-3 and >=3 years after the enrolment, respectively. The highest quartile of
      the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17
      (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10);
      p=0.042) of developing authentic metachronous gastric cancers. Similar trends
      were seen for EMX1 and NKX6-1. CONCLUSIONS: Assessment of the degree of an
      epigenetic field defect is a promising cancer risk marker that takes account of
      life history.

PMID- 25379952
TI  - Trazodone and cognitive performance in Alzheimer disease.

PMID- 25379954
TI  - Valence-space compatibility effects depend on situated motor fluency in both
      right- and left-handers.
AB  - According to the body specificity hypothesis, the way we interact with our
      environment participates in our conceptualization of concepts and word meanings.
      For instance, valence is associated to horizontal space because of the motor
      fluency by which one acts with one's dominant hand. We propose that the decisive
      factor in the compatibility effects between valence and lateral actions is the
      interaction between the fluency of response movement and the situational
      constraints of the task. In a valence judgement task with positive and negative
      words, right-handers (Experiment 1) and left-handers (Experiment 2) responded
      with lateralized actions of either their dominant or their nondominant hand. To
      do so, we used a response device that was either congruent or noncongruent with
      the fluency of the response hand. Results highlighted that when the response
      device was congruent with the fluency of the responding hand, response times to
      positive evaluations were shorter than those to negative evaluations. Conversely,
      when the response device was noncongruent with the fluency of the responding
      hand, we observed faster responses for negative evaluations than for positive
      evaluations. Furthermore, we obtained similar patterns for right- and left
      handers, supporting the idea that compatibility effects are driven by the
      situated fluency of the responding hand. 

PMID- 25379953
TI  - Deficiency of the tumor promoter gene wip1 induces insulin resistance.
AB  - Diabetes is a growing health care issue, and prediabetes has been established as
      a risk factor for type 2 diabetes. Prediabetes is characterized by deregulated
      glucose control, and elucidating pathways which govern this process is critical.
      We have identified the wild-type (WT) p53-inducible phosphatase (WIP1)
      phosphatase as a regulator of glucose homeostasis. Initial characterization of
      insulin signaling in WIP1 knockout (WIP1(KO)) murine embryo fibroblasts
      demonstrated reduced insulin-mediated Ak mouse transforming activation. In order
      to assess the role of WIP1 in glucose homeostasis, we performed metabolic
      analysis on mice on a low-fat chow diet (LFD) and high fat diet (HFD). We
      observed increased expression of proinflammatory cytokines in WIP1(KO) murine
      embryo fibroblasts, and WIP1(KO) mice fed a LFD and a HFD. WIP1(KO) mice
      exhibited glucose intolerance and insulin intolerance on a LFD and HFD. However,
      the effects of WIP1 deficiency cause different metabolic defects in mice on a LFD
      and a HFD. WIP1(KO) mice on a LFD develop hepatic insulin resistance, whereas
      this is not observed in HFD-fed mice. Mouse body weights and food consumption
      increase slightly over time in LFD-fed WT and WIP1(KO) mice. Leptin levels are
      increased in LFD-fed WIP1(KO) mice, compared with WT. In contrast, HFD-fed
      WIP1(KO) mice are resistant to HFD-induced obesity, have decreased levels of food
      consumption, and decreased leptin levels compared with HFD-WT mice. WIP1 has been
      shown to regulate the nuclear factor kappa-light-chain-enhancer of activated B
      cells pathway, loss of which leads to increased inflammation. We propose that
      this increased inflammation triggers insulin resistance in WIP1(KO) mice on LFD
      and HFD. 

PMID- 25379955
TI  - Investigation of the use of spectral clustering for the analysis of molecular
      data.
AB  - Spectral clustering involves placing objects into clusters based on the
      eigenvectors and eigenvalues of an associated matrix. The technique was first
      applied to molecular data by Brewer [J. Chem. Inf. Model. 2007, 47, 1727-1733]
      who demonstrated its use on a very small dataset of 125 COX-2 inhibitors. We have
      determined suitable parameters for spectral clustering using a wide variety of
      molecular descriptors and several datasets of a few thousand compounds and
      compared the results of clustering using a nonoverlapping version of Brewer's use
      of Sarker and Boyer's algorithm with that of Ward's and k-means clustering. We
      then replaced the exact eigendecomposition method with two different approximate
      methods and concluded that Singular Value Decomposition is the most appropriate
      method for clustering larger compound collections of up to 100,000 compounds. We
      have also used spectral clustering with the Tversky coefficient to generate two
      sets of clusters linked by a common set of eigenvalues and have used this novel
      approach to cluster sets of fragments such as those used in fragment-based drug
      design.

PMID- 25379951
TI  - Highly specific plasmonic biosensors for ultrasensitive microRNA detection in
      plasma from pancreatic cancer patients.
AB  - MicroRNAs (miRs) are small noncoding RNAs that regulate mRNA stability and/or
      translation. Because of their release into the circulation and their remarkable
      stability, miR levels in plasma and other biological fluids can serve as
      diagnostic and prognostic disease biomarkers. However, quantifying miRs in the
      circulation is challenging due to issues with sensitivity and specificity. This
      Letter describes for the first time the design and characterization of a
      regenerative, solid-state localized surface plasmon resonance (LSPR) sensor based
      on highly sensitive nanostructures (gold nanoprisms) that obviates the need for
      labels or amplification of the miRs. Our direct hybridization approach has
      enabled the detection of subfemtomolar concentration of miR-X (X = 21 and 10b) in
      human plasma in pancreatic cancer patients. Our LSPR-based measurements showed
      that the miR levels measured directly in patient plasma were at least 2-fold
      higher than following RNA extraction and quantification by reverse transcriptase
      polymerase chain reaction. Through LSPR-based measurements we have shown nearly 4
      fold higher concentrations of miR-10b than miR-21 in plasma of pancreatic cancer
      patients. We propose that our highly sensitive and selective detection approach
      for assaying miRs in plasma can be applied to many cancer types and disease
      states and should allow a rational approach for testing the utility of miRs as
      markers for early disease diagnosis and prognosis, which could allow for the
      design of effective individualized therapeutic approaches. 

PMID- 25379956
TI  - Proteins and peptides: The need to improve them as promising therapeutics for
      ulcerative colitis.
AB  - The present review briefly describes the nature, type and pathogenesis of
      ulcerative colitis, and explores the potential use of peptides and proteins in
      the treatment of inflammatory bowel disease, especially ulcerative colitis.
      Intestinal absorption and the barrier mechanism of peptide and protein drugs are
      also discussed, with special emphasis on various strategies which make these
      drugs better therapeutics having high specificity, potency and molecular
      targeting ability. However, the limitation of such therapeutics are oral
      administration, poor pharmacokinetic profile and decreased bioavailability. The
      recent findings illustrated in this review will be helpful in designing the
      peptide/protein drugs as a promising treatment of choice for ulcerative colitis. 

PMID- 25379957
TI  - Ferromagnetic ordering in superatomic solids.
AB  - In order to realize significant benefits from the assembly of solid-state
      materials from molecular cluster superatomic building blocks, several criteria
      must be met. Reproducible syntheses must reliably produce macroscopic amounts of
      pure material; the cluster-assembled solids must show properties that are more
      than simply averages of those of the constituent subunits; and rational changes
      to the chemical structures of the subunits must result in predictable changes in
      the collective properties of the solid. In this report we show that we can meet
      these requirements. Using a combination of magnetometry and muon spin relaxation
      measurements, we demonstrate that crystallographically defined superatomic solids
      assembled from molecular nickel telluride clusters and fullerenes undergo a
      ferromagnetic phase transition at low temperatures. Moreover, we show that when
      we modify the constituent superatoms, the cooperative magnetic properties change
      in predictable ways. 

PMID- 25379958
TI  - Probing the relative orientation of molecules bound to DNA by second-harmonic
      generation.
AB  - We develop a model to probe the relative orientation of two second-order
      polarizable daunomycin molecules that are intercalated into a DNA duplex using
      optical second-harmonic (SH) generation. The SH field generated by the daunomycin
      molecules interfere with each other. Because the interference depends on the
      relative orientation of the daunomycin molecules, we can control the interference
      by changing the number of base pairs separating them. The relative orientation
      changes as the number of base pairs separating them, multiplied by 36 degrees ,
      which is the twist angle between neighboring base pairs. In this paper, we derive
      a set of relationships between the relative angle of the molecules and the
      nonlinear susceptibility elements, and we calculate the SH field generated by the
      DNA/molecular-pair complex attached to an isotropic dielectric sphere.
      Calculations reveal that the SH intensity varies periodically with the relative
      orientation of the two chromophores in the plane perpendicular to the helical
      axis. The predicted periodicity is in close agreement with experimental results.
      Structural changes induced by foreign molecules binding to DNA will change the
      relative orientation of the two chromophores and thereby change the SH
      interference pattern. We discuss the potential of this SH interference method in
      providing a new way to probe structural changes induced by the formation of
      biomolecule complexes. An important feature of the method is that it is label
      free, that is, the binding molecule, in this case, daunomycin, is not tagged. 

PMID- 25379959
TI  - A magnetic induction heating system with multi-cascaded coils and adjustable
      magnetic circuit for hyperthermia.
AB  - Based on the characteristics of cancer cells that cannot survive in an
      environment with temperature over 42  degrees C, a magnetic induction heating
      system for cancer treatment is developed in this work. First, the methods and
      analyses for designing the multi-cascaded coils magnetic induction hyperthermia
      system are proposed, such as internal impedance measurement of power generator,
      impedance matching of coils, and analysis of the system. Besides, characteristics
      of the system are simulated by a full-wave package for engineering optimization.
      Furthermore, by considering the safety factor of patients, a two-sectional needle
      is designed for hyperthermia. Finally, this system is employed to test the liver
      of swine in ex-vivo experiments, and through Hematoxylin and Eosin (H&E) stain
      and NADPH oxidase activity assay, the feasibility of this system is verified. 

PMID- 25379960
TI  - Regional principal color based saliency detection.
AB  - Saliency detection is widely used in many visual applications like image
      segmentation, object recognition and classification. In this paper, we will
      introduce a new method to detect salient objects in natural images. The approach
      is based on a regional principal color contrast modal, which incorporates low
      level and medium-level visual cues. The method allows a simple computation of
      color features and two categories of spatial relationships to a saliency map,
      achieving higher F-measure rates. At the same time, we present an interpolation
      approach to evaluate resulting curves, and analyze parameters selection. Our
      method enables the effective computation of arbitrary resolution images.
      Experimental results on a saliency database show that our approach produces high
      quality saliency maps and performs favorably against ten saliency detection
      algorithms. 

PMID- 25379961
TI  - Interplay of the bacterial ribosomal A-site, S12 protein mutations and
      paromomycin binding: a molecular dynamics study.
AB  - The conformational properties of the aminoacyl-tRNA binding site (A-site), and
      its surroundings in the Escherichia coli 30S ribosomal subunit, are of great
      relevance in designing antibacterial agents. The 30S subunit A-site is near
      ribosomal protein S12, which neighbors helices h27 and H69; this latter helix, of
      the 50S subunit, is a functionally important component of an intersubunit bridge.
      Experimental work has shown that specific point mutations in S12 (K42A, R53A)
      yield hyper-accurate ribosomes, which in turn confers resistance to the
      antibiotic 'paromomycin' (even when this aminoglycoside is bound to the A-site).
      Suspecting that these effects can be elucidated in terms of the local atomic
      interactions and detailed dynamics of this region of the bacterial ribosome, we
      have used molecular dynamics simulations to explore the motion of a fragment of
      the E. coli ribosome, including the A-site. We found that the ribosomal regions
      surrounding the A-site modify the conformational space of the flexible A-site
      adenines 1492/93. Specifically, we found that A-site mobility is affected by
      stacking interactions between adenines A1493 and A1913, and by contacts between
      A1492 and a flexible side-chain (K43) from the S12 protein. In addition, our
      simulations reveal possible indirect pathways by which the R53A and K42A
      mutations in S12 are coupled to the dynamical properties of the A-site. Our work
      extends what is known about the atomistic dynamics of the A-site, and suggests
      possible links between the biological effects of hyper-accurate mutations in the
      S12 protein and conformational properties of the ribosome; the implications for
      S12 dynamics help elucidate how the miscoding effects of paromomycin may be
      evaded in antibiotic-resistant mutants of the bacterial ribosome. 

PMID- 25379962
TI  - Effect of cardiac resynchronization therapy with implantable cardioverter
      defibrillator versus cardiac resynchronization therapy with pacemaker on
      mortality in heart failure patients: results of a high-volume, single-centre
      experience.
AB  - AIMS: There are limited and contradictory data on the effects of CRT with
      implantable cardioverter defibrillator (CRT-D) on mortality as compared with CRT
      with pacemaker (CRT-P). METHODS AND RESULTS: We evaluated the long-term outcome
      of patients implanted with a CRT-D or CRT-P device in our high-volume single
      centre experience. Data on all-cause mortality were derived from clinic visits
      and the Hungarian National Healthcare Fund Death Registry. Kaplan-Meier survival
      analyses and multivariate Cox regression models were used to evaluate all-cause
      mortality in patients with CRT-D vs. CRT-P, stratified by the aetiology of
      cardiomyopathy. From 2000 to 2011, 1122 CRT devices, 693 CRT-P (LVEF 28.2 +/-
      7.4%) and 429 CRT-D (LVEF 27.6 +/- 6.4%), were implanted at our centre. During
      the median follow-up of 28 months, 379 patients died from any cause, 250 patients
      (36%) with an implanted CRT-P and 129 patients (30%) with an implanted CRT-D.
      There was no evidence of mortality benefit in patients implanted with a CRT-D
      compared with a CRT-P in the total cohort [hazard ratio (HR) 0.98, 95% confidence
      interval (CI) 0.73-1.32, P = 0.884]. In patients with ischaemic cardiomyopathy,
      CRT-D treatment was associated with a significant 30% risk reduction in all-cause
      mortality compared with an implanted CRT-P (HR 0.70, 95% CI 0.51-0.97, P = 0.03).
      In non-ischaemic patients, there was no mortality benefit of CRT-D over CRT-P (HR
      0.98, 95% CI 0.73-1.32, P = 0.894, interaction P-value = 0.15). CONCLUSIONS: In
      heart failure patients with ischaemic cardiomyopathy, CRT-D was associated with a
      mortality benefit compared with CRT-P, but no benefit of CRT-D over CRT-P in
      mortality was observed in non-ischaemic cardiomyopathy.

PMID- 25379969
TI  - Red blood cell nitric oxide synthase activation is increased in patients with
      sickle cell hemoglobin C disease.

PMID- 25379970
TI  - A decrease of regulatory T cells and altered expression of NK receptors are
      observed in subacute sclerosing panencephalitis.
AB  - Subacute sclerosing panencephalitis (SSPE) is caused by a persistent measles
      virus infection. Regulatory mechanisms can be responsible for a failure of
      immunosurveillance in children with SSPE. In this study, peripheral blood cells
      of 71 patients with SSPE and 57 children with other diseases were compared
      phenotypically. The proportions of CD4(+), CD8(+) T, and NK cells were
      homogenous, whereas total CD3(+) T and Treg (CD4(+)CD25(+)CD152(+)) cells were
      decreased in patients with SSPE. The proportion of CD8(+) T cells expressing the
      inhibitory NKG2A(+) receptor was also decreased (1.7% +/- 1.7% vs. 2.6% +/- 1.9%,
      p = 0.007) in patients with SSPE, whereas the proportion of NK cells expressing
      activating NKG2C was increased compared with the control group (30.0% +/- 17.3%
      vs. 22.2% +/- 17.0%, p = 0.039). The decrease in the number of cells with
      regulatory phenotype, the lower presence of the inhibitory NK receptors on CD8(+)
      cells, and higher activating NK receptors on NK cells in SSPE indicate an
      upregulation of these cell types that favors their response. This state of active
      immune response may be caused by chronic stimulation of viral antigens leading to
      altered regulatory pathways.

PMID- 25379971
TI  - The fibrin network in diabetes: its role in thrombosis risk.
AB  - Despite advances in therapy, individuals with diabetes remain at high risk of
      cardiovascular disease and their clinical prognosis following vascular ischemia
      is worse than that of individuals with normal glucose metabolism. Current
      evidence suggests that the enhanced thrombotic environment in diabetes represents
      a key abnormality contributing to the adverse clinical outcome following vascular
      occlusion in this population. Thrombus formation occurs following a complex
      process that encompasses both the cellular (represented by platelets) and fluid
      phase of coagulation, involving a large number of plasma proteins. In the current
      review, we discuss some of the abnormalities encountered in coagulation factor
      levels or activity in diabetes. In particular, we focus on the pathological
      processes that lead to the formation of compact fibrin networks with increased
      resistance to lysis. We describe current knowledge on the mechanistic pathways
      responsible for the increased fibrin-related thrombosis risk in diabetes and
      explore alternative therapeutic targets. We also briefly cover various management
      strategies that may help control the enhanced thrombotic milieu in this
      population of patients at high cardiovascular risk. 

PMID- 25379973
TI  - "Blindsight" and subjective awareness of fearful faces: Inversion reverses the
      deficits in fear perception associated with core psychopathic traits.
AB  - Though emotional faces preferentially reach awareness, the present study utilised
      both objective and subjective indices of awareness to determine whether they
      enhance subjective awareness and "blindsight". Under continuous flash
      suppression, participants localised a disgusted, fearful or neutral face
      (objective index), and rated their confidence (subjective index). Psychopathic
      traits were also measured to investigate their influence on emotion perception.
      As predicted, fear increased localisation accuracy, subjective awareness and
      "blindsight" of upright faces. Coldhearted traits were inversely related to
      subjective awareness, but not "blindsight", of upright fearful faces. In a follow
      up experiment using inverted faces, increased localisation accuracy and
      awareness, but not "blindsight", were observed for fear. Surprisingly, awareness
      of inverted fearful faces was positively correlated with coldheartedness. These
      results suggest that emotion enhances both pre-conscious processing and the
      qualitative experience of awareness, but that pre-conscious and conscious
      processing of emotional faces rely on at least partially dissociable cognitive
      mechanisms. 

PMID- 25379972
TI  - Effective targeting of DC-SIGN by alpha-fucosylamide functionalized gold
      nanoparticles.
AB  - Dendritic Cells (DCs), the most potent antigen-presenting cells, play a critical
      role in the detection of invading pathogens, which are recognized also by
      multiple carbohydrate-specific receptors. Among them, DC-SIGN is one of the best
      characterized, with high-mannose and Lewis-type glycan specificity. In this
      study, we present a potent DC-SIGN targeting device developed using gold
      nanoparticles functionalized with alpha-fucosyl-beta-alanyl amide. The
      nanoparticles bound to cellular DC-SIGN and induced internalization as
      effectively as similar particles coated with comparable amounts of Lewis(X)
      oligosaccharide. They were found to be neutral toward dendritic cell maturation
      and IL-10 production, thus envisaging a possible use as targeted imaging tools
      and antigen delivery devices. 

PMID- 25379975
TI  - An enantioselective total synthesis of Sch-725674.
AB  - An enantioselective total synthesis of Sch-725674, a unique 14-membered
      macrolactone, has been accomplished in 13 steps. The step-wise dithiane
      alkylation served as a strategic step to assemble the upper and lower fragments
      of the molecule, whereas cross metathesis reaction, Yamaguchi macrolactonization
      and a substrate controlled stereoselective reduction are used as key steps to
      complete the total synthesis. 

PMID- 25379974
TI  - E-cadherin as an epithelial barrier protein in exhaled breath condensate.
AB  - Airway epithelium plays an important role as a physical barrier and a modulator
      of allergic response. Junctions between cells provide epithelial integrity and
      barrier function. The aim of this study was to investigate the influence of atopy
      on airway epithelial integrity in asthma and to measure E-cadherin levels in
      exhaled breath condensate as an indicator epithelial damage. A total of 74
      patients with asthma (35 atopic and 39 non-atopic) and 39 healthy children were
      enrolled in this case-control study. Sociodemographic characteristics and asthma
      severity parameters in the last three-month period were recorded and pulmonary
      function tests were performed. Blood samples were obtained to measure serum
      immunoglobulin E (IgE) levels and peripheral blood eosinophil count, and exhaled
      breath condensate (EBC) was obtained to measure E-cadherin.EBC E-cadherin levels
      were significantly lower in the asthmatics when compared to non-atopic controls
      (0.109 (0.076) versus 0.191 (0.184) ng mL(-1) respectively, p = 0.01). Atopic and
      non-atopic asthmatic groups had lower EBC E-cadherin levels compared to the
      control group. (0.112 (0.060) ng ml(-1), 0.106 (0.089) ng ml(-1) and 0.191
      (0.184) ng ml(-1), p = 0.02 and p < 0.01 respectively). However, EBC E-cadherin
      levels were not different between atopic and non-atopic asthmatics. The results
      of our study support the role of E-cadherin in the pathogenesis of asthma.
      However, the absence of difference in E-cadherin levels between atopic and non
      atopic asthmatics suggests that allergic sensitization is not the primary factor
      for development of epithelial barrier dysfunction in asthma.

PMID- 25379976
TI  - Physical activity behavior, barriers to activity, and opinions about a smartphone
      based physical activity intervention among rural residents.
AB  - BACKGROUND: Rural Americans engage in less physical activity (PA) and experience
      higher rates of consequent health problems (i.e., obesity, cardiovascular
      disease) than urban Americans. Although geographic barriers have historically
      made this population hard to reach, rural individuals are increasingly gaining
      access to smartphones. Thus, the purpose of this study was to evaluate PA
      behavior and barriers to PA among rural residents and to gauge their
      receptiveness to a smartphone-based PA intervention that is currently in the
      development stage. MATERIALS AND METHODS: Rural Floridian adults (n=113), 18
      years of age and older, completed surveys to assess PA behavior, PA barriers, and
      opinions about an intervention to increase PA. Specifically, they were asked to
      imagine a program that would require them to do PA with their mobile phones and
      whether they viewed intended aspects of the program as helpful. The present work
      is therefore formative research that sought to determine the feasibility and
      acceptability of a smartphone-based intervention among rural residents. RESULTS
      of the survey will inform the development of a tailored, smartphone-based PA
      intervention. RESULTS: The 37.2% of participants with low PA levels (<600
      metabolic equivalent [MET]-min per week) were more likely to report personal and
      environmental barriers to PA than the 47.8% of participants with moderate PA
      levels (>=600 MET-min per week). More barriers were reported among participants
      who self-reported as white and among participants of older age, lower education
      level, and lower socioeconomic status. Additionally, 75.9% of participants
      reported features of the intervention as at least somewhat helpful. CONCLUSIONS:
      The growing ubiquity of smartphones among rural residents, combined with
      participants' positive response to the program description, supports the
      acceptability of a smartphone-based PA intervention for rural communities. Given
      the participants' receptiveness, future research should evaluate the efficacy of
      smartphone-delivered health behavior interventions among this population.

PMID- 25379977
TI  - Microvascular abnormalities in patients with early systemic sclerosis: less
      severe morphological changes than in patients with definite disease.
AB  - OBJECTIVES: To evaluate the morphological and functional abnormalities of the
      microcirculation associated with markers of vascular injury in patients with
      early systemic sclerosis (SSc). METHOD: Forty-six patients with early SSc were
      compared with 80 patients with definite SSc, 40 patients with primary Raynaud's
      phenomenon (PRP), and 45 healthy subjects. Widefield nailfold capillaroscopy
      (NFC) (10-25 * magnification), videocapillaroscopy (200 * magnification), and
      laser Doppler imaging (LDI) assessment were performed in all participants. The
      number of capillaries/mm, enlarged, giant and ramified capillaries,
      microhaemorrhages, and the avascular score were determined by widefield NFC and
      videocapillaroscopy. Fingertip blood flow (FBF) was measured using LDI before and
      after cold stimulus (CS). Serum endothelin-1 (ET-1), von Willebrand factor (vWF),
      and transforming growth factor beta-1 (TGF-beta1) were measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Upon both widefield NFC and
      videocapillaroscopy, patients with early SSc showed significantly higher numbers
      of capillaries/mm, lower enlarged and giant capillaries, and a lower avascular
      score than definite SSc patients (p < 0.001). They also had more enlarged
      capillaries, microhaemorrhages and a higher avascular score compared to PRP and
      controls (p < 0.001). FBF before and after CS were significantly higher in
      controls than in PRP, early SSc, and definite SSc patients (p < 0.001), with no
      difference between early and definite SSc. Serum levels of ET-1, vWF, and TGF
      beta1 were similar between early and definite SSc patients. CONCLUSIONS: Early
      SSc patients showed functional changes and vascular injury marker levels similar
      to patients with established disease. Nonetheless, the morphological changes were
      less severe in early SSc, thus providing an opportunity for further prevention of
      vasculopathy progression.

PMID- 25379978
TI  - Human use of antibiotics marketed for pets: an alarming trend.

PMID- 25379979
TI  - Era of specialty pharmaceuticals expands opportunities for pharmacists.

PMID- 25379980
TI  - Implementation of targeted medication adherence interventions within a community
      chain pharmacy practice: The Pennsylvania Project.
AB  - OBJECTIVE: To identify facilitators and barriers to implementing targeted
      medication adherence interventions in community chain pharmacies, and describe
      adaptations of the targeted intervention and organizational structure within each
      individual pharmacy practice. DESIGN: Qualitative study. SETTING: Central and
      western Pennsylvania from February to April 2012. PARTICIPANTS: Rite Aid
      pharmacists staffed at the 118 Pennsylvania Project intervention sites. MAIN
      OUTCOME MEASURES: Qualitative analysis of pharmacists' perceptions of
      facilitators and barriers experienced, targeted intervention and organizational
      structure adaptations implemented, and training and preparation prior to
      implementation. RESULTS: A total of 15 key informant interviews were conducted
      from February to April 2012. Ten pharmacists from "early adopter" practices and
      five pharmacists from "traditionalist" practices were interviewed. Five themes
      emerged regarding the implementation of targeted interventions, including all
      pharmacists' need to understand the relationship of patient care programs to
      their corporation's vision; providing individualized, continual support and
      mentoring to pharmacists; anticipating barriers before implementation of patient
      care programs; encouraging active patient engagement; and establishing best
      practices regarding implementation of patient care services. CONCLUSION: This
      qualitative analysis revealed that there are a series of key steps that can be
      taken before the execution of targeted interventions that may promote successful
      implementation of medication therapy management in community chain pharmacies.

PMID- 25379982
TI  - Services provided by community pharmacies in Wayne County, Michigan: a comparison
      by ZIP code characteristics.
AB  - OBJECTIVE: To document the availability of selected pharmacy services and out-of
      pocket cost of medication throughout a diverse county in Michigan and to assess
      possible associations between availability of services and price of medication
      and characteristics of residents of the ZIP codes in which the pharmacies were
      located. DESIGN: Cross-sectional telephone survey of pharmacies coupled with ZIP
      code-level census data. SETTING: 503 pharmacies throughout the 63 ZIP codes of
      Wayne County, MI. MAIN OUTCOME MEASURES: The out-of-pocket cost for a 30 days'
      supply of levothyroxine 50 mcg and brand-name atorvastatin (Lipitor-Pfizer) 20
      mg, availability of discount generic drug programs, home delivery of medications,
      hours of pharmacy operation, and availability of pharmacy-based immunization
      services. Census data aggregated at the ZIP code level included race, annual
      household income, age, and number of residents per pharmacy. RESULTS: The overall
      results per ZIP code showed that the average cost for levothyroxine was $10.01 +/
      $2.29 and $140.45 + $14.70 for Lipitor. Per ZIP code, the mean (+/- SD)
      percentages of pharmacies offering discount generic drug programs was 66.9% +/-
      15.0%; home delivery of medications was 44.5% +/- 22.7%; and immunization for
      influenza was 46.7% +/- 24.3% of pharmacies. The mean (+/- SD) hours of operation
      per pharmacy per ZIP code was 67.0 +/- 25.2. ZIP codes with higher household
      income as well as higher percentage of residents being white had lower
      levothyroxine price, greater percentage of pharmacies offering discount generic
      drug programs, more hours of operation per week, and more pharmacy-based
      immunization services. The cost of Lipitor was not associated with any ZIP code
      characteristic. CONCLUSION: Disparities in the cost of generic levothyroxine, the
      availability of services such as discount generic drug programs, hours of
      operation, and pharmacy-based immunization services are evident based on race and
      household income within this diverse metropolitan county.

PMID- 25379981
TI  - Minimizing out-of-pocket prescription drug costs for Medicare beneficiaries: not
      just 'a drop in the bucket'.
AB  - OBJECTIVE: To identify the frequency of uptake and financial impact of four cost
      minimization strategies used to assist Medicare beneficiaries in lowering their
      out-of-pocket (OOP) costs. DESIGN: Cost-savings analysis. SETTING: Twelve
      outreach events were conducted in six different cities throughout Northern and
      Central California during the 2013 Medicare open enrollment period. PARTICIPANTS:
      Noninstitutionalized Medicare beneficiaries from various socioeconomic
      backgrounds, including those receiving Medicaid. MAIN OUTCOME MEASURES: Potential
      OOP cost savings for the upcoming year. RESULTS: In total, 621 beneficiaries were
      assisted. Part D plan optimization was performed for 535 beneficiaries; the
      findings indicated that 435 (81%) could save money (average: $1,334) by switching
      plans in the upcoming year. The results also demonstrated that 28 beneficiaries
      could save money (mean: $1,274) through a patient assistance program. In total,
      16 beneficiaries had self-reported income and/or assets that were low enough to
      qualify for additional governmental assistance through the low-income subsidy.
      Finally, less costly therapeutic alternatives were identified for 7 beneficiaries
      and prescribers accepted recommendations for change in 6 (85%) such cases. In
      total, beneficiaries could realize more than $770,000 in potential OOP savings
      from the performed interventions. CONCLUSION: Targeted assistance to
      beneficiaries through a variety of cost-lowering strategies can help
      significantly reduce OOP costs and thus may also result in lower cost-related
      medication nonadherence and improved beneficiary outcomes.

PMID- 25379983
TI  - Heart failure assessment at the community pharmacy level: a feasibility pilot
      study.
AB  - BACKGROUND: A key element missing in disease-management programs for heart
      failure (HF) is participation of the community pharmacist. The purpose of this
      study is to determine if a simple and efficient clinical tool will allow
      community pharmacists to identify patients at risk for worsening HF. DESIGN: The
      One Minute Clinic for Heart Failure (TOM-C HF) was developed as a simple six-item
      symptom screening tool to be used during routine patient/customer interactions.
      SETTING: Ten community pharmacies located in the upper Midwest. PATIENTS: Self
      identified HF patients. RESULTS: 121 unique patients were evaluated over a 12
      month period. The application of this clinical tool took between 1 and 5 minutes
      in over 80% of the interactions. Seventy-five patients (62%) had one or more
      signs or symptoms of worsening HF. The most common symptoms detected included
      edema (39%) and increased shortness of breath (17%). Self-reported weight gain of
      more than 5 pounds was seen in 19% of patients. CONCLUSION: The TOM-C HF tool was
      used to identify patients in a time-efficient manner in the community pharmacy
      setting who appear to be developing worsening HF. Inclusion of the community
      pharmacists as an early screen for HF decompensation may be an important link in
      disease-management programs to help reduce hospital readmission rates.

PMID- 25379984
TI  - Progress toward vaccines for cholera, dengue, malaria, and Ebola.

PMID- 25379985
TI  - Dalbavancin, tedizolid phosphate, oritavancin diphosphate, and vedolizumab.

PMID- 25379986
TI  - Medication regimen complexity indices: a tool to focus MTM efforts?

PMID- 25379988
TI  - Micro+nanotexturing of substrates to enhance ligand-assisted cancer cell
      isolation.
AB  - This paper presents a simple approach to create a two-tiered surface for superior
      cancer cell isolation. The idea is inspired by the interactions of cells with a
      nanotextured basement membrane. The texture mimicked the extracellular matrix and
      basement membrane for superior target cell adhesion. Prepared micro+nanotextured
      surfaces showed enhanced cell capture. Preparation of the two-tiered surface was
      done using micro- and nanotexturing and was easily reproducible. It has been
      shown before that the larger surface area of a nanotextured surface assists the
      cell's attachment through surface-anchored ligands. Taking it a step further,
      ligand functionalized two-level micro+nanotextured surfaces improved the
      sensitivity of the cancer cell isolation over simple flat nanotexturing. The
      isolation efficiency increased by 208% compared to the surface with a single
      level nanotexture. The two-tiered surface was compatible with previously reported
      nanotextured devices used for cancer cell isolation. Micro-texture on the glass
      surface was created using simple sand gritting, followed by reactive ion etching
      (RIE) of the entire surface. The approach could create large surface areas within
      a short time while maintaining superior cell isolation efficiency. 

PMID- 25379987
TI  - On a matter of seminal importance.
AB  - Egg and sperm have, understandably, been the "stars" of mammalian fertilization
      biology, particularly because artificial reproductive technologies allow for
      fertilization to occur outside of the female reproductive tract without other
      apparent contributions from either sex. Yet, recent research, including an
      exciting new paper, reveals unexpected and important contributions of seminal
      plasma to fertility. For example, seminal plasma proteins play critical roles in
      modulating female reproductive physiology, and a new study in mice demonstrates
      that effects of some of these proteins on the female can even affect the health
      of her progeny. Furthermore, although several actions of seminal plasma have been
      conserved across taxa, male accessory glands and their products are diverse -
      even among mammals. Taken together, these studies suggest that the actions of
      seminal plasma components are important to understand, and also to consider in
      future development of assisted reproductive technologies (ART) for humans, farm
      species and endangered species of mammals. 

PMID- 25379989
TI  - Perovskite ceramic nanoparticles in polymer composites for augmenting bone tissue
      regeneration.
AB  - There is increasing interest in the use of nanoparticles as fillers in polymer
      matrices to develop biomaterials which mimic the mechanical, chemical and
      electrical properties of bone tissue for orthopaedic applications. The objective
      of this study was to prepare poly(epsilon-caprolactone) (PCL) nanocomposites
      incorporating three different perovskite ceramic nanoparticles, namely, calcium
      titanate (CT), strontium titanate (ST) and barium titanate (BT). The tensile
      strength and modulus of the composites increased with the addition of
      nanoparticles. Scanning electron microscopy indicated that dispersion of the
      nanoparticles scaled with the density of the ceramics, which in turn played an
      important role in determining the enhancement in mechanical properties of the
      composite. Dielectric spectroscopy revealed improved permittivity and reduced
      losses in the composites when compared to neat PCL. Nanofibrous scaffolds were
      fabricated via electrospinning. Induction coupled plasma-optical emission
      spectroscopy indicated the release of small quantities of Ca(+2), Sr(+2), Ba(+2)
      ions from the scaffolds. Piezo-force microscopy revealed that BT nanoparticles
      imparted piezoelectric properties to the scaffolds. In vitro studies revealed
      that all composites support osteoblast proliferation. Expression of osteogenic
      genes was enhanced on the nanocomposites in the following order: PCL/CT > PCL/ST
      > PCL/BT > PCL. This study demonstrates that the use of perovskite nanoparticles
      could be a promising technique to engineer better polymeric scaffolds for bone
      tissue engineering. 

PMID- 25379990
TI  - Pharmacological interventions for somatoform disorders in adults.
AB  - BACKGROUND: Somatoform disorders are characterised by chronic, medically
      unexplained physical symptoms (MUPS). Although different medications are part of
      treatment routines for people with somatoform disorders in clinics and private
      practices, there exists no systematic review or meta-analysis on the efficacy and
      tolerability of these medications. We aimed to synthesise to improve optimal
      treatment decisions. OBJECTIVES: To assess the effects of pharmacological
      interventions for somatoform disorders (specifically somatisation disorder,
      undifferentiated somatoform disorder, somatoform autonomic dysfunction, and pain
      disorder) in adults. SEARCH METHODS: We searched the Cochrane Depression, Anxiety
      and Neurosis Review Group's Specialised Register (CCDANCTR) (to 17 January 2014).
      This register includes relevant randomised controlled trials (RCTs) from The
      Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and
      PsycINFO (1967 to date). To identify ongoing trials, we searched
      ClinicalTrials.gov, Current Controlled Trials metaRegister, the World Health
      Organization International Clinical Trials Registry Platform, and the Chinese
      Clinical Trials Registry. For grey literature, we searched ProQuest Dissertation
      & Theses Database, OpenGrey, and BIOSIS Previews. We handsearched conference
      proceedings and reference lists of potentially relevant papers and systematic
      reviews and contacted experts in the field. SELECTION CRITERIA: We selected RCTs
      or cluster RCTs of pharmacological interventions versus placebo, treatment as
      usual, another medication, or a combination of different medications for
      somatoform disorders in adults. We included people fulfilling standardised
      diagnostic criteria for somatisation disorder, undifferentiated somatoform
      disorder, somatoform autonomic dysfunction, or somatoform pain disorder. DATA
      COLLECTION AND ANALYSIS: One review author and one research assistant
      independently extracted data and assessed risk of bias. Primary outcomes included
      the severity of MUPS on a continuous measure, and acceptability of treatment.
      MAIN RESULTS: We included 26 RCTs (33 reports), with 2159 participants, in the
      review. They examined the efficacy of different types of antidepressants, the
      combination of an antidepressant and an antipsychotic, antipsychotics alone, or
      natural products (NPs). The duration of the studies ranged between two and 12
      weeks.One meta-analysis of placebo-controlled studies showed no clear evidence of
      a significant difference between tricyclic antidepressants (TCAs) and placebo for
      the outcome severity of MUPS (SMD -0.13; 95% CI -0.39 to 0.13; 2 studies, 239
      participants; I(2) = 2%; low-quality evidence). For new-generation
      antidepressants (NGAs), there was very low-quality evidence showing they were
      effective in reducing the severity of MUPS (SMD -0.91; 95% CI -1.36 to -0.46; 3
      studies, 243 participants; I(2) = 63%). For NPs there was low-quality evidence
      that they were effective in reducing the severity of MUPS (SMD -0.74; 95% CI 
      0.97 to -0.51; 2 studies, 322 participants; I(2) = 0%).One meta-analysis showed
      no clear evidence of a difference between TCAs and NGAs for severity of MUPS (SMD
      -0.16; 95% CI -0.55 to 0.23; 3 studies, 177 participants; I(2) = 42%; low-quality
      evidence). There was also no difference between NGAs and other NGAs for severity
      of MUPS (SMD -0.16; 95% CI -0.45 to 0.14; 4 studies, 182 participants; I(2) =
      0%).Finally, one meta-analysis comparing selective serotonin reuptake inhibitors
      (SSRIs) with a combination of SSRIs and antipsychotics showed low-quality
      evidence in favour of combined treatment for severity of MUPS (SMD 0.77; 95% CI
      0.32 to 1.22; 2 studies, 107 participants; I(2) = 23%).Differences regarding the
      acceptability of the treatment (rate of all-cause drop-outs) were neither found
      between NGAs and placebo (RR 1.01, 95% CI 0.64 to 1.61; 2 studies, 163
      participants; I(2) = 0%; low-quality evidence) or NPs and placebo (RR 0.85, 95%
      CI 0.40 to 1.78; 3 studies, 506 participants; I(2) = 0%; low-quality evidence);
      nor between TCAs and other medication (RR 1.48, 95% CI 0.59 to 3.72; 8 studies,
      556 participants; I(2) =14%; low-quality evidence); nor between antidepressants
      and the combination of an antidepressant and an antipsychotic (RR 0.80, 95% CI
      0.25 to 2.52; 2 studies, 118 participants; I(2) = 0%; low-quality evidence).
      Percental attrition rates due to adverse effects were high in all antidepressant
      treatments (0% to 32%), but low for NPs (0% to 1.7%).The risk of bias was high in
      many domains across studies. Seventeen trials (65.4%) gave no information about
      random sequence generation and only two (7.7%) provided information about
      allocation concealment. Eighteen studies (69.2%) revealed a high or unclear risk
      in blinding participants and study personnel; 23 studies had high risk of bias
      relating to blinding assessors. For the comparison NGA versus placebo, there was
      relatively high imprecision and heterogeneity due to one outlier study. Although
      we identified 26 studies, each comparison only contained a few studies and small
      numbers of participants so the results were imprecise. AUTHORS' CONCLUSIONS: The
      current review found very low-quality evidence for NGAs and low-quality evidence
      for NPs being effective in treating somatoform symptoms in adults when compared
      with placebo. There was some evidence that different classes of antidepressants
      did not differ in efficacy; however, this was limited and of low to very low
      quality. These results had serious shortcomings such as the high risk of bias,
      strong heterogeneity in the data, and small sample sizes. Furthermore, the
      significant effects of antidepressant treatment have to be balanced against the
      relatively high rates of adverse effects. Adverse effects produced by medication
      can have amplifying effects on symptom perceptions, particularly in people
      focusing on somatic symptoms without medical causes. We can only draw conclusions
      about short-term efficacy of the pharmacological interventions because no trial
      included follow-up assessments. For each of the comparisons where there were
      available data on acceptability rates (NGAs versus placebo, NPs versus placebo,
      TCAs versus other medication, and antidepressants versus a combination of an
      antidepressant and an antipsychotic), no clear differences between the
      intervention and comparator were found.Future high-quality research should be
      carried out to determine the effectiveness of medications other than
      antidepressants, to compare antidepressants more thoroughly, and to follow-up
      participants over longer periods (the longest follow up was just 12 weeks).
      Another idea for future research would be to include other outcomes such as
      functional impairment or dysfunctional behaviours and cognitions as well as the
      classical outcomes such as symptom severity, depression, or anxiety.

PMID- 25379992
TI  - Procyanidin B2 inhibits inflammasome-mediated IL-1beta production in
      lipopolysaccharide-stimulated macrophages.
AB  - SCOPE: Macrophage stimulation with bacterial LPS triggers inflammasome
      activation, resulting in pro-inflammatory IL-1beta cytokine maturation and
      secretion. IL-1beta underlies the pathologies of many diseases, including type-2
      diabetes. Thus, the modulation of the inflammatory response through bioactive
      food compounds, such as procyanidins, is a powerful tool to promote homeostasis.
      METHODS AND RESULTS: To determine the role of procyanidin B2 in inflammasome
      activation, LPS-primed THP-1-macrophages were supplemented with or without
      procyanidin B2 . Western blot analysis of COX2 , iNOS, p65, NLRP3 and IL-1beta
      was performed followed by p65 supershift assay, in vivo caspase-1 activation
      assay and NO, IL-1beta and IL-6 determination. Procyanidin B2 mediated inhibition
      of inflammasome activation includes the inactivation of the NF-kappaB signalling
      pathway, the first stage required for the transcription of inflammasome
      precursors, through the inhibition of p65 nuclear expression and DNA binding,
      resulting in the transcriptional repression of target genes, such as COX2 , iNOS
      and production of IL-6 and NO. Furthermore, procyanidin B2 decreases NLRP3 and
      pro-IL-1beta cytoplasmic pools, limiting components of inflammasome activation
      and impeding inflammasome assembly and caspase-1 activation, and finally
      secretion of active IL-1beta. CONCLUSION: This study provides the first evidence
      that procyanidin B2 inhibits inflammasome activation and IL-1beta secretion
      during LPS-induced acute inflammation in human macrophages.

PMID- 25379994
TI  - An expedient approach to synthesize fluorescent 3-substituted 4H-quinolizin-4
      ones via (eta(4)-vinylketene)-Fe(CO)3 complexes.
AB  - An efficient and practical methodology for the synthesis of 3-substituted 4H
      quinolizin-4-ones using (eta(4)-vinylketene)-Fe(CO)3 complexes as key
      intermediates has been developed. The advantage of this transformation lies in
      the use of simple and readily available starting materials and mild carbonylation
      conditions. The fluorescent properties of these compounds were determined and the
      quantum yield was obtained, ranging from 0.04 to 0.36 depending on the
      substituent. 

PMID- 25379995
TI  - Synthesis and cytotoxicity of triterpenoids derived from betulin and betulinic
      acid via click chemistry.
AB  - In this study, a series of triazole substituted betulin and betulinic acid
      derivatives was designed and synthesized via click chemistry at C-30 position.
      Eighteen target compounds were evaluated in vitro for their antitumor activities
      against leukemia cell-line HL-60. Seventeen compounds have not reported before.
      The cytotoxic experiment showed that most of betulinic acid derived triazoles
      have higher cytotoxic profile than betulinic acid. Among them, compound 30-[4-(4
      fluorophenyl)-1H-1,2,3-triazol-1-yl] betulinic acid (7b) showed the best IC50
      value (1.3 MUM) against leukemia cell-line HL-60 (eight- to ninefold higher
      potency than betulinic acid).

PMID- 25379993
TI  - Healthy lifestyle and risk of breast cancer among postmenopausal women in the
      European Prospective Investigation into Cancer and Nutrition cohort study.
AB  - Breast cancer is the most common cancer among women and prevention strategies are
      needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was
      generated to investigate the joint effect of modifiable lifestyle factors on
      postmenopausal breast cancer risk. The study included 242,918 postmenopausal
      women from the multinational European Prospective Investigation into Cancer and
      Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed
      at baseline. The HLIS was constructed from five factors (diet, physical activity,
      smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to
      categories of each component, for which higher values indicate healthier
      behaviours. Hazard ratios (HR) were estimated by Cox proportional regression
      models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases
      were identified. There was a 3% lower risk of breast cancer per point increase of
      the HLIS. Breast cancer risk was inversely associated with a high HLIS when
      fourth versus second (reference) categories were compared [adjusted HR = 0.74;
      95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category
      of the HLIS was associated with a lower risk for hormone receptor double positive
      (adjusted HR = 0.81, 95% CI: 0.67-0.98) and hormone receptor double negative
      breast cancer (adjusted HR = 0.60, 95% CI: 0.40-0.90). Findings suggest having a
      high score on an index of combined healthy behaviours reduces the risk of
      developing breast cancer among postmenopausal women. Programmes which engage
      women in long term health behaviours should be supported. 

PMID- 25379996
TI  - To cut is to cure? Elective resection after percutaneous drainage for
      diverticular abscess.

PMID- 25379997
TI  - A prospective multicenter clinical study of extralevator abdominoperineal
      resection for locally advanced low rectal cancer.
AB  - BACKGROUND: Recent studies have shown that extralevator abdominoperineal
      resection has the potential for reduced circumferential resection margin
      involvement, intraoperative bowl perforation, and local recurrence rates;
      however, it has been suggested that extended resection may be associated with
      increased morbidity because of the formation of a larger perineal defect.
      OBJECTIVE: This study was undertaken to demonstrate the feasibility and
      complications of extralevator abdominoperineal resection for locally advanced low
      rectal cancer in China. DESIGN: This was a prospective cohort study. SETTING: The
      study was conducted at 7 university hospitals throughout China. PATIENTS: A total
      of 102 patients underwent this procedure for primary locally advanced low rectal
      cancer between August 2008 and October 2011. MAIN OUTCOME MEASURES: The main
      outcome measures comprised circumferential resection margin involvement,
      intraoperative perforation, postoperative complications, and local recurrence.
      RESULTS: The most common complications included sexual dysfunction (40.5%),
      perineal complications (23.5%), urinary retention (18.6%), and chronic perineal
      pain (13.7%). Chronic perineal pain was associated with coccygectomy (p < 0.001),
      and the pain gradually eased over time. Reconstruction of the pelvic floor with
      biological mesh was associated with a lower rate of perineal dehiscence (p =
      0.006) and overall perineal wound complications (p = 0.02) in comparison with
      primary closure. A positive circumferential margin was demonstrated in 6 (5.9%)
      patients, and intraoperative perforations occurred in 4 (3.9%) patients. All
      circumferential margin involvements and intraoperative perforations were located
      anteriorly. The local recurrence was 4.9% at a median follow-up of 44 months
      (range, 18-68 months). LIMITATIONS: This was a nonrandomized, uncontrolled study.
      CONCLUSIONS: Extralevator abdominoperineal resection performed in the prone
      position for low rectal cancer is a relatively safe approach with acceptable
      circumferential resection margin involvement, intraoperative perforations, and
      local recurrences. Reconstruction of the pelvic floor with biological mesh might
      lower the rate of perineal wound complications (see Video, Supplemental Digital
      Content 1, http://links.lww.com/DCR/A161).

PMID- 25379998
TI  - Adjuvant chemotherapy for t1 node-positive colon cancers provides significant
      survival benefit.
AB  - BACKGROUND: Contemporary treatment of node-positive (N+) colon cancer consists of
      adjuvant chemotherapy; however, randomized data supporting this practice were
      derived from lesions T2 or greater. Minimal data exist regarding the use and need
      for adjuvant chemotherapy in T1N+ disease. OBJECTIVE: The aim of this study was
      to determine treatment trends and the effects of adjuvant chemotherapy on T1N+
      colon cancers by using the National Cancer Database. DESIGN: This was a
      retrospective study. Baseline demographics, tumor, and cancer treatment
      characteristics were compared. Groups were matched on the propensity to receive
      chemotherapy. Adjusted long-term survival stratified by chemotherapy use was
      compared by using the Kaplan-Meier method with the log-rank test. Predictors of
      not receiving chemotherapy were identified by using a multivariable logistic
      regression model. SETTINGS: Data were collected from the National Cancer
      Database, which collects cancer data from over 1500 cancer centers. PATIENTS: We
      identified patients from 1998 to 2006 with T1N+ disease, excluding those with
      metastatic disease or previous cancer. Patients were stratified based on whether
      or not they received chemotherapy. MAIN OUTCOME MEASURES: The primary outcome
      measure of this study was long-term survival. RESULTS: Three thousand one hundred
      thirty-seven patients had T1N+ disease; 70.6% (n = 2216) received chemotherapy,
      and utilization significantly increased from 1998 to 2011 (p < 0.001). Unadjusted
      analysis revealed that patients treated with chemotherapy were statistically
      younger and healthier, and had shorter postoperative lengths of stay (all p <
      0.001). Unadjusted 5-year survival was higher in patients receiving chemotherapy
      (87.9% vs 63.0% in patients with no chemotherapy; p < 0.001) and this persisted
      after propensity matching with (83.4% and 63.0% in patients with or without
      chemotherapy; p < 0.001). Only age (OR, 0.29; p < 0.001) predicted not receiving
      chemotherapy. LIMITATIONS: Limitations include potential selection bias as well
      as the inability to compare disease-free survival/recurrence. CONCLUSIONS:
      Adjuvant chemotherapy appears to significantly improve long-term survival in
      patients receiving chemotherapy in T1N+ disease. Thus, the use of chemotherapy in
      T1N+ disease is justified and provides a highly significant survival benefit.

PMID- 25379999
TI  - Subtotal colectomy in severe ulcerative and Crohn's colitis: what benefit does
      the laparoscopic approach confer?
AB  - BACKGROUND: Comparative outcome data for laparoscopic and open subtotal colectomy
      in IBD are lacking and often difficult to interpret owing to low case volumes,
      heterogeneity in case mix, and variation in laparoscopic technique. OBJECTIVE:
      This study aimed to determine the safety of laparoscopic subtotal colectomy in
      severe colitis and to determine whether the laparoscopic approach improved short
      term outcomes in comparison with the open approach. DESIGN: This was a
      retrospective cohort study using data from a prospectively maintained clinical
      database. SETTING: This study was conducted at a single center, Mount Sinai
      Hospital, Toronto. PATIENTS: All patients undergoing subtotal colectomy for
      either ulcerative or Crohn's colitis between 2000 and 2011 were included.
      INTERVENTION: A standardized operative technique was used for both laparoscopic
      and open subtotal colectomies. Cases performed by non-laparoscopic surgeons were
      excluded. MAIN OUTCOME MEASURES: Perioperative outcome measures were operative
      duration, estimated blood loss, total morphine requirement, and length of
      postoperative stay. Postoperative outcome measures were the rates of minor and
      major complications. RESULTS: Laparoscopic subtotal colectomies were performed in
      131 of 290 cases (45.2%). Nine patients required conversion to an open procedure
      (6.9%). The uptake of laparoscopic subtotal colectomy increased from 10.2% in
      2000/2001 to 71.7% in 2010/2011. Regression analysis with propensity-score
      adjustment for operative approach revealed that the operative duration was 25.5
      minutes longer in laparoscopic cases (95% CI 12.3-38.6; p < 0.001), but that
      patients experienced fewer minor complications (OR 0.47; 95% CI 0.23-0.96; p =
      0.04) and required less morphine (adjusted difference, -72.8 mg; 95% CI 4.9-141;
      p = 0.04). LIMITATIONS: The inherent selection bias of this retrospective cohort
      study may not be accounted for by multivariate analysis with propensity-score
      adjustment. CONCLUSIONS: Laparoscopic subtotal colectomy is safe and may reduce
      the rate of minor postoperative complications. The increase in operative duration
      reflects the technical demands associated with this procedure (see Video,
      Supplemental Digital Content 1, http://links.lww.com/DCR/A160).

PMID- 25380000
TI  - Initial surgical management of ulcerative colitis in the biologic era.
AB  - BACKGROUND: The initial minimum operation for ulcerative colitis is a total
      abdominal colectomy. Healthy patients may undergo proctectomy at the same time;
      however, for ill patients, proctectomy is delayed. Since the introduction of
      biologic medications in 2005, ulcerative colitis medical management has changed
      dramatically. OBJECTIVE: We examined how operative management for ulcerative
      colitis has changed from the prebiologic to biologic eras. DESIGN: We conducted a
      retrospective review of data on patients with ulcerative colitis who were
      included in the Nationwide Inpatient Sample database. SETTINGS: This study was
      conducted at a single university. PATIENTS: A total of 1,547,852 patients with
      ulcerative colitis who were admitted to a US hospital from 1991 to 2011 were
      included in the study. MAIN OUTCOME MEASURES: We examined patients whose initial
      operation consisted of total abdominal colectomy without proctectomy versus a
      total proctocolectomy with or without a pouch. We also examined which operation
      was done at the time of the construction of an ileoanal pouch. Patients who
      underwent colectomy and pouch construction in the same hospitalization were
      compared with those who received pouch formation at a subsequent hospitalization.
      RESULTS: Ulcerative colitis-related admissions rose by 170% during the years
      examined, and the number of patients who required total abdominal colectomy
      increased by 44%. Total abdominal colectomy increased by 15%, as opposed to total
      proctocolectomy (p < 0.001). Pouch construction at a subsequent operation
      increased by 16% (p = 0.002). Since 2008, total abdominal colectomy has surpassed
      total proctocolectomy as the most common initial surgical intervention for
      ulcerative colitis. LIMITATIONS: The Nationwide Inpatient Sample is a
      retrospective database, and we were limited to examining the variables within it.
      CONCLUSIONS: Total abdominal colectomy is currently the most common initial
      operation for patients with ulcerative colitis, and an ileoanal pouch is more
      frequently constructed at a subsequent hospitalization. These trends coincide
      with the initiation of biologic treatments and may imply that patients are
      acutely ill at the time of initial operation. Alternately, there may be surgeon
      perceived bias of increased surgical risk or a shift in care to specialized
      surgeons for pouch construction.

PMID- 25380001
TI  - Accuracy of CT enterography and magnetic resonance enterography imaging to detect
      lesions preoperatively in patients undergoing surgery for Crohn's disease.
AB  - BACKGROUND: CT enterography and magnetic resonance enterography have emerged as
      first-line imaging technologies for the evaluation of the gastrointestinal tract
      in Crohn's disease. OBJECTIVE: The purpose of this work was to evaluate the
      accuracy of these imaging modalities to identify Crohn's disease lesions
      preoperatively. DESIGN: This was a retrospective chart review. SETTINGS: The
      study was conducted at a single institution. PATIENTS: Seventy-six patients with
      Crohn's disease with preoperative CT enterography and/or magnetic resonance
      enterography were included in the study. MAIN OUTCOME MEASURES: The number of
      stenoses, fistulas, and abscesses on CT enterography and/or magnetic resonance
      enterography before surgery were compared with operative findings. RESULTS: Forty
      patients (53%) were women, 46 (60%) underwent surgery for recurrent Crohn's
      disease, and 46 (57%) had previous abdominal surgery. Thirty-six (47%) had a
      preoperative CT enterography and 43 (57%) had a preoperative magnetic resonance
      enterography. CT enterography sensitivity was 75% for stenosis and 50% for
      fistula. MRE sensitivity was 68% for stenosis and 60% for fistula. The negative
      predictive values of CT enterography and magnetic resonance enterography for
      stenosis were very low (54% and 65%) and were 85% and 81% for fistula. CT
      enterography had 76% accuracy for stenosis and 79% for fistula; magnetic
      resonance enterography had 78% accuracy for stenosis and 85% for fistula. Both
      were accurate for abscess. False-negative rates for CT enterography were 50% for
      fistula and 25% for stenosis. False-negative rates for magnetic resonance
      enterography were 40% for fistula and 32% for stenosis. Unexpected intraoperative
      findings led to modification of the planned surgical procedure in 20 patients
      (26%). LIMITATIONS: This study was limited by its small sample size, its
      retrospective nature, and that some studies were performed at outside
      institutions. CONCLUSIONS: CT enterography and magnetic resonance enterography in
      patients with Crohn's disease were accurate for the identification of abscesses
      but not for fistulas or stenoses. Surgeons should search for additional lesions
      intraoperatively. Patients should be appropriately counseled regarding the need
      for unexpected interventions (see Video, Supplemental Digital Content 1,
      http://links.lww.com/DCR/A162).

PMID- 25380003
TI  - Risk of catheter-associated deep venous thrombosis in inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease confers a hypercoagulable state. A large
      number of these patients require central venous access in the form of
      peripherally inserted central catheters for long-term intravenous therapies. Our
      clinical observations suggested that these patients had a higher incidence of
      catheter-associated deep venous thrombosis than that of the general population.
      OBJECTIVE: The aim of this study was to examine the relationship between IBD and
      catheter-associated deep venous thrombosis. DESIGN: A retrospective chart review
      was conducted of all patients who underwent peripherally inserted central
      catheter line placement between 2009 and 2011. SETTING: This study was performed
      at a single-institution tertiary referral center. PATIENTS: All patients who
      underwent peripherally inserted central catheter line placement were identified.
      OUTCOME MEASURES: The risk of catheter-associated deep venous thrombosis in IBD
      patients was assessed. This risk was compared with known risk factors such as
      malnutrition, malignancy, diabetes mellitus, and tobacco use. Multivariate
      analysis was performed. Catheter size, indication for placement, and vein
      location of catheter-associated deep venous thrombosis were identified in the IBD
      population. RESULTS: There were 7179 peripherally inserted central catheter lines
      placed during the study period; the overall incidence of catheter-associated deep
      venous thrombosis was 2.1% (148/7179). The incidence of catheter-associated deep
      venous thrombosis among patients with IBD was 6.8% (9/132). The incidence of
      catheter-associated deep venous thrombosis among non-IBD patients was 1.9%
      (139/7047) (relative risk, 3.5; 95% CI, 1.8-6.6; p < 0.001). The incidence of
      catheter-associated deep venous thrombosis was increased for patients with
      malnutrition (4.8%, 30/628, p < 0.001) and increasing age (95% CI, 1.01-1.12; p =
      0.02). There was no increased incidence of catheter-associated deep venous
      thrombosis for patients with diabetes mellitus (1.6%, 25/1574, p < 0.14),
      malignancy (2.8%, 30/1041, p = 0.06), or tobacco use (1.6%, 31/1938, p = 0.10).
      After multivariate analysis, IBD, malnutrition, and increasing age were found to
      be significant risk factors for the development of catheter-associated deep
      venous thrombosis. LIMITATIONS: The inability to track the number of catheter
      days, the inaccuracy of administrative data, the lack of outpatient follow-up,
      and the small number of events in the study cohort were limitations of this
      study. CONCLUSIONS: This is the first study to demonstrate IBD as an independent
      risk factor to the development of catheter-associated deep venous thrombosis. The
      placement of a peripherally inserted central catheter line in IBD should be
      utilized selectively.

PMID- 25380002
TI  - Factors associated with 30-day readmission after restorative proctocolectomy with
      IPAA: a national study.
AB  - BACKGROUND: Hospital readmission has been identified by many payers as a
      surrogate for surgical quality. The 30-day readmission rate and factors
      associated with hospital readmission after restorative proctocolectomy with IPAA
      have not been well studied. OBJECTIVE: The purpose of this work was to identify
      the rate of and factors associated with hospital readmission within 30 days of
      restorative proctocolectomy with IPAA. DESIGN: A retrospective review of patients
      undergoing IPAA from 2009 to 2012 in the University HealthSystem Consortium
      database was performed. Hospitals were stratified into quartiles according to the
      number of cases performed annually. SETTING: This study was conducted using a
      national database of university hospitals. PATIENTS: A total of 4952 patients
      within the 4-year study period were included in the analysis. MAIN OUTCOME
      MEASURES: The primary outcome measured was readmission within 30 days of
      discharge. RESULTS: The 30-day readmission rate was 22.8% overall, although high
      volume centers performed significantly better than low-volume centers (high vs
      low volume: 19.7% vs 28.2%; p < 0.001). When controlling for confounding
      variables, multivariate analysis identified female sex (OR, 1.191; p = 0.02),
      government-based (vs private) insurance (OR, 1.364; p < 0.001), and higher
      preoperative severity of illness (OR, 1.491; p = 0.001) to be associated with
      readmission. In addition, a significant volume-dependent relationship on 30-day
      readmission was identified, wherein undergoing operation at the higher-volume
      hospitals was protective for predicting readmission. Hierarchical regression
      modeling indicated that 31% of the variation in readmission rates among
      individual hospitals was accounted for by hospital volume. LIMITATIONS: This
      study was limited by its retrospective nature and limited postoperative
      complication data. CONCLUSIONS: The national 30-day readmission after IPAA
      creation was 22.8%, at least double that of other colorectal procedures. This
      high rate of readmission was mitigated by centers performing the highest volume
      of cases. Avoidance of referral to centers performing very few of these
      procedures annually may improve perioperative outcomes and reduce associated
      morbidity.

PMID- 25380004
TI  - Laparoscopic peritoneal lavage for Hinchey III diverticulitis: is it as effective
      as it is applicable?
AB  - BACKGROUND: Over the past few years, the laparoscopic peritoneal lavage has
      emerged as a therapeutic alternative to standard resection procedures. However,
      its effectiveness and applicability remain debatable. OBJECTIVE: The aim of this
      study was to assess laparoscopic lavage in controlling abdominal sepsis secondary
      to purulent peritonitis. DESIGN: This study was conducted as a retrospective
      analysis of prospectively collected data. SETTING: This study was conducted at a
      single tertiary care institution. PATIENTS: Patients requiring emergency surgery
      for perforated diverticulitis and generalized peritonitis between June 2006 and
      June 2013 were identified from a prospective database. Laparoscopic assessment
      was considered in all of the hemodynamically stable patients, and laparoscopic
      lavage was performed according to intraoperative strict criteria. MAIN OUTCOME
      MEASURES: Primary outcomes were the effectiveness and applicability of
      laparoscopic lavage. Secondarily, feasibility, morbidity, and mortality were also
      assessed. RESULTS: Seventy-five patients required emergency surgery for
      generalized peritonitis secondary to perforated diverticulitis. Forty-six
      patients who underwent laparoscopy presented a purulent generalized (Hinchey III)
      peritonitis and were examined under the intention-to-treat basis to perform a
      laparoscopic lavage. Thirty-two patients (70.0%; 95% CI 56.2-82.7) had no
      previous episodes of diverticulitis. Thirty-six patients (78.0%; 95% CI 66.3
      90.1) had free air on a CT scan. The conversion rate was 4% (95% CI 0-10). The
      feasibility of the method was 96.0% (95% CI 90.4-100), and its applicability was
      59.0% (95% CI 44.8-73.2). Median operative time was 89 minutes (range, 40-200
      minutes). Postoperative morbidity was 24.0% (95% CI 11.7-36.3), and the mortality
      rate was 0%. We registered 5 failures, and all of them underwent reoperation. The
      effectiveness of the procedure was 85% (95% CI 76-93). LIMITATIONS: This was a
      single-institution retrospective study. CONCLUSIONS: The effectiveness of
      laparoscopic lavage seems to be high. Although its applicability is lower, it
      could be applied in more than half of patients requiring emergency surgery. This
      alternative strategy should be considered when laparoscopic assessment reveals
      Hinchey III diverticulitis.

PMID- 25380005
TI  - Stimulation of the efferent limb before ileostomy closure: a randomized clinical
      trial.
AB  - BACKGROUND: Postoperative ileus is the most common complication after ileostomy
      closure with an increase in morbidity, hospital stay, and health care costs.
      OBJECTIVE: The aim of this study is to assess the utility of a new technique for
      reducing postoperative ileus after protective ileostomy closure. DESIGN: This is
      a prospective randomized study registered at ClinicalTrials.gov (NCT01881594).
      Patients were randomly assigned to undergo either stimulation through the
      efferent limb of the ileostomy before surgery or nonstimulation before surgery.
      SETTING: This study was conducted at the Department of Surgery of the Virgen de
      la Arrixaca Clinical University Hospital (Murcia). PATIENTS: Seventy patients
      underwent surgery for ileostomy closure. In 35 patients, during the 2 weeks
      before surgery, daily stimulation of the defunctionalized stomal segment was
      performed by using a thick solution (500 mL of physiological saline associated
      with 30 g of thickening agent, Nestle Resource, Vevey, Switzerland). In the other
      35 patients, stimulation was not performed before surgery. MAIN OUTCOME MEASURES:
      The primary outcome was postoperative ileus. The secondary outcomes included time
      to tolerating a diet and postoperative stay. RESULTS: Both groups of patients
      were homogenous for demographic data, characteristics of the first rectal cancer
      operation, and intersurgery periods. After ileostomy closure, the stimulated
      group of patients had an earlier return to oral tolerance (1.06 vs 2.57 days; p =
      0.007) and passage of flatus or stool (1.14 vs 2.85 days; p <0.001) than the
      nonstimulated group of patients. The incidence of postoperative ileus (2.85% vs
      20%; p = 0.024) and hospital stay (2.49 vs 4.61 days; p = 0.002) was also lower
      in the stimulated patients. LIMITATIONS: Small numbers of patients means that no
      definitive statements can be made regarding the effectiveness of this technique.
      CONCLUSIONS: Stimulation of the efferent limb of the ileostomy before closure is
      a safe technique that reduces postoperative ileus and fosters early intestinal
      transit and oral tolerance with a shorter postoperative hospital stay.

PMID- 25380006
TI  - Evolving practice patterns in the management of acute colonic diverticulitis: a
      population-based analysis.
AB  - BACKGROUND: There is increasing evidence to support the use of percutaneous
      abscess drainage, laparoscopy, and primary anastomosis in managing acute
      diverticulitis. OBJECTIVE: The aim of this study was to evaluate how practices
      have evolved and to determine the effects on clinical outcomes. DESIGN: This is a
      population-based retrospective cohort study using administrative discharge data.
      SETTING: This study was conducted in Ontario, Canada. PATIENTS: All patients had
      been hospitalized for a first episode of acute diverticulitis (2002-2012). MAIN
      OUTCOME MEASURES: Temporal changes in treatment strategies and outcomes were
      evaluated by using the Cochran-Armitage test for trends. Multivariable logistic
      regression with generalized estimating equations was used to test for trends
      while adjusting for patient characteristics. RESULTS: There were 18,543 patients
      hospitalized with a first episode of diverticulitis, median age 60 years
      (interquartile range, 48-74). From 2002 to 2012, there was an increase in the
      proportion of patients admitted with complicated disease (abscess, perforation),
      32% to 38%, yet a smaller proportion underwent urgent operation, 28% to 16% (all
      p < 0.001). The use of percutaneous drainage increased from 1.9% of admissions in
      2002 to 3.3% in 2012 (p < 0.001). After adjusting for changes in patient and
      disease characteristics over time, the odds of urgent operation decreased by 0.87
      per annum (95% CI, 0.85-0.89). In those undergoing urgent surgery (n = 3873), the
      use of laparoscopy increased (9% to 18%, p <0.001), whereas the use of the
      Hartmann procedure remained unchanged (64%). During this time, in-hospital
      mortality decreased (2.7% to 1.9%), as did the median length of stay (5 days,
      interquartile range, 3-9; to 3 days, interquartile range, 2-6; p <0.001).
      LIMITATIONS: There is the potential for residual confounding, because clinical
      parameters available for risk adjustment were limited to fields existing within
      administrative data. CONCLUSIONS: There has been an increase in the use of
      nonoperative and minimally invasive strategies in treating patients with a first
      episode of acute diverticulitis. However, the Hartmann procedure remains the most
      frequently used urgent operative approach. Mortality and length of stay have
      improved during this time.

PMID- 25380007
TI  - The use of negative-pressure wound therapy in pilonidal sinus disease: a
      randomized controlled trial comparing negative-pressure wound therapy versus
      standard open wound care after surgical excision.
AB  - BACKGROUND: Pilonidal sinus disease is associated with significant morbidity
      after surgical treatment with regard to wound healing. Recent case studies
      suggested that negative-pressure wound therapy as primary treatment following
      surgical excision may shorten the duration of wound healing. OBJECTIVE: The
      purpose of this randomized controlled trial was to evaluate the role of vacuum
      therapy in pilonidal sinus disease: negative-pressure wound therapy versus
      standard open wound care after surgical excision. METHODS: Patients were randomly
      assigned to either negative-pressure wound therapy for 2 weeks or standard open
      wound healing. The primary end point of the study was the time to complete wound
      healing. Secondary end points were visual analog scale score, wound size ratio at
      day 14 (ie, wound healing rate), time to resume daily activities, and recurrence
      within 6 months after wound closure. RESULTS: Forty-nine patients were included
      in the study: 24 patients were treated with vacuum therapy, and 25 patients
      underwent standard open wound care. Complete wound healing was achieved at a
      median of 84 days in the vacuum therapy group versus 93 days in control patients
      (p = 0.44). The wound size ratio was significantly lower in the vacuum therapy
      group (0.30 versus 0.57, p = 0.02), ie, higher wound healing rate in the first 2
      weeks. There was no difference in visual analog scale scores and disease
      recurrence between both groups. The time to resume full daily activities after
      surgery was 27 days in the patients undergoing vacuum therapy and 29 days in the
      control patients (p = 0.92). LIMITATIONS: This study is limited by the small
      number of patients, the lack of blinding to patients and doctors, and the absence
      of patient quality-of-life evaluation. CONCLUSION: It is feasible to apply vacuum
      therapy in the treatment of pilonidal sinus disease, and it has a positive effect
      on wound size reduction in the first 2 weeks. However, there is no difference in
      time to complete wound healing and time to resume daily life activities.

PMID- 25380008
TI  - Acute health care resource utilization for ileostomy patients is higher than
      expected.
AB  - BACKGROUND: Patients requiring an ileostomy following colorectal surgery are at
      risk for increased health-care utilization after discharge. Prior studies
      evaluating postoperative ileostomy care may underestimate health-care utilization
      by reporting only "same-institution" readmission rates. OBJECTIVE: The aim of
      this study was to determine the rates of health-care utilization of new ostomates
      within 30 days of discharge in a multicenter environment. DESIGN: This is a
      retrospective cohort study. SETTINGS: This study was conducted at acute-care,
      community hospitals in California, Florida, Nebraska, and New York. PATIENTS:
      Adult patients who underwent colorectal surgery with primary anastomosis,
      colostomy, or ileostomy between July 2009 and September 2010 were identified.
      MAIN OUTCOME MEASURES: The primary outcome measured was hospital-based acute
      care, defined as hospital readmission or emergency department visit, at any
      hospital within 30 days of surgery. Multivariate regression models were used to
      compare the outcomes across groups. RESULTS: Overall, 75,136 patients underwent
      colectomy with most receiving a primary anastomosis (79.3%), whereas colostomies
      were created in 12.8% and ileostomies were created in 8.0%. Diagnoses of
      colorectal cancer (36.1%) or diverticular disease (22.0%) were most common.
      Patients with a colostomy (18.8%; adjusted odds ratio [AOR], 1.23 [95% CI, 1.17
      1.30]) or ileostomy (36.1%; AOR, 2.28 [95% CI 2.15-2.42]) were significantly more
      likely than patients with a primary anastomosis (16.2%) to have a hospital-based
      acute-care encounter within 30 days of discharge. Among patients undergoing
      ileostomy, postoperative infection, renal failure, and dehydration were the most
      common diagnoses for hospital-based acute-care events. Overall, 20% of these
      encounters occurred at hospitals other than where the index surgery occurred.
      LIMITATIONS: Coding accuracy, the inability to capture events occurring in
      physician offices, and the retrospective study design were limitations of the
      study. CONCLUSIONS: Patients undergoing colorectal surgery with an ileostomy
      return to the hospital after discharge twice as frequently as those with a
      primary anastomosis or colostomy, often to hospitals other than the primary
      institution. As postdischarge health-care utilization becomes a measured quality
      metric, it is increasingly important to help these patients to safely transition
      to home.

PMID- 25380009
TI  - Clinical and financial impact of hospital readmissions after colorectal
      resection: predictors, outcomes, and costs.
AB  - BACKGROUND: After passage of the Affordable Care Act, 30 -day hospital
      readmissions have come under greater scrutiny. Excess readmissions for certain
      medical conditions and procedures now result in penalizations on all Medicare
      reimbursements. OBJECTIVE: The purpose of this work was to define the risk
      factors, outcomes, and costs of 30-day readmissions after colorectal surgery.
      DESIGN: Adults undergoing colorectal surgery were studied using data from the
      University HealthSystem Consortium. Univariate and multivariable analyses were
      used to identify patient-related risk factors for, and 30-day outcomes of,
      readmission after colorectal surgery. SETTINGS: This study was conducted at an
      academic hospital and its affiliates. PATIENTS: Adults >=18 years of age who
      underwent colorectal surgery for cancer, diverticular disease, IBD, or benign
      tumors between 2008 and 2011 were included in this study. MAIN OUTCOME MEASURES:
      Readmission within 30 days of index discharge was the main outcome measured.
      RESULTS: A total of 70,484 patients survived the index hospitalization after
      colorectal surgery; 9632 (13.7%) were readmitted within 30 days of discharge. The
      strongest independent predictors of readmission were length of stay >=4 days (OR
      1.44; 95% CI 1.32-1.57), stoma (OR 1.54; 95% CI 1.46-1.51), and discharge to
      skilled nursing (OR 1.62; 95% CI 1.49-1.76) or rehabilitation facility (OR 2.93;
      95% CI 2.53-3.40). Of those readmitted, half of the readmissions occurred within
      7 days, 13% required the intensive care unit, 6% had a reoperation, and 2% died
      during the readmission stay. The median combined total direct hospital cost was
      more than 2 times higher ($26,917 vs $13,817; p < 0.001) for readmitted than for
      nonreadmitted patients. LIMITATIONS: Follow-up was limited to 30 days after
      initial discharge. CONCLUSIONS: Readmissions after colorectal resection occur
      frequently and incur a significant financial burden on the health-care system.
      Future studies aimed at targeted interventions for high-risk patients may reduce
      readmissions and curb escalating health-care costs.

PMID- 25380010
TI  - Elective resection versus observation after nonoperative management of
      complicated diverticulitis with abscess: a systematic review and meta-analysis.
AB  - BACKGROUND: Initial management of diverticulitis with abscess formation has
      progressed from a surgical emergency to nonoperative management with antibiotics
      and percutaneous drainage followed by delayed resection. Controversy has arisen
      regarding the necessity of elective surgery, when nonoperative management has
      successfully resolved the index attack. OBJECTIVE: The aim of this systematic
      review was to analyze the literature to determine the recurrence rate in those
      patients who were successfully managed nonoperatively and determine the role of
      elective surgical resection. DATA SOURCES: An electronic literature search of
      PubMed, MEDLINE, EMBASE, and the Cochrane Database of Collected Reviews performed
      from 1986 to 2014. The search terms used were as follows: "diverticulitis,"
      "abscess," "diverticular abscess," "percutaneous drainage," and "surgery." STUDY
      SELECTION: Studies included for review evaluated the management of diverticular
      abscesses and the subsequent role of delayed elective resection. INTERVENTIONS:
      All of the studies were systematically reviewed and underwent a meta-analysis.
      MAIN OUTCOME MEASURES: End points were the need for surgery and recurrent attacks
      without surgery. RESULTS: Twenty-two studies reporting a total of 1051 patients
      with acute diverticulitis with abscess formation (modified Hinchey grades IB and
      II) were included in the review. Percutaneous drainage was successful in 49%
      patients (diameter, >3 cm) and antibiotic therapy in 14% patients. Urgent surgery
      during the index hospitalization was performed in 30% of patients, elective
      resection in 36%, and no surgery in 35%. Recurrence rates were high, with 39% in
      patients awaiting elective resection and 18% in the nonsurgery group, with an
      overall recurrence rate of 28%. Of the whole cohort, only 28% had no surgery and
      no recurrence during follow-up. LIMITATIONS: Sample size, heterogeneity,
      selection and treatment bias, and limited follow-up of included studies were
      limitations to this study. CONCLUSIONS: The evidence from the literature is weak
      but still suggests that complicated diverticulitis with abscess formation is
      associated with a high probability of resective surgery, whereas conservative
      management may result in chronic or recurrent diverticular symptoms.

PMID- 25380011
TI  - Laparoscopic resection rectopexy with preservation of the superior rectal artery,
      natural orifice specimen extraction, and assessment of anastomotic perfusion
      using indocyanine green imaging in rectal prolapse.

PMID- 25380012
TI  - Ventral mesh rectopexy: procedure of choice for the surgical treatment of pelvic
      organ prolapse?

PMID- 25380013
TI  - Ventral mesh rectopexy: is this the new standard for surgical treatment of pelvic
      organ prolapse?

PMID- 25380015
TI  - Parastomal hernia prevention: is it all about mesh reinforcement?

PMID- 25380016
TI  - The author replies.

PMID- 25380017
TI  - Anal fistulas.

PMID- 25380024
TI  - Costs and benefits of non-invasive fetal RhD determination.
AB  - OBJECTIVE: Non-invasive fetal Rhesus (Rh) D genotyping, using cell-free fetal DNA
      (cffDNA) in the maternal blood, allows targeted antenatal anti-RhD prophylaxis in
      unsensitized RhD-negative pregnant women. The purpose of this study was to
      determine the cost and benefit of this approach as compared to routine antenatal
      anti-RhD prophylaxis for all unsensitized RhD-negative pregnant women, as is the
      current policy in the province of Alberta, Canada. METHODS: This study was a
      decision analysis based on a theoretical population representing the total number
      of pregnancies in Alberta over a 1-year period (n = 69 286). A decision tree was
      created that outlined targeted prophylaxis for unsensitized RhD-negative pregnant
      women screened for cffDNA (targeted group) vs routine prophylaxis for all
      unsensitized RhD-negative pregnant women (routine group). Probabilities at each
      decision point and costs associated with each resource were calculated from local
      clinical and administrative data. Outcomes measured were cost, number of women
      sensitized and doses of Rh immunoglobulin (RhIG) administered. RESULTS: The
      estimated cost per pregnancy for the routine group was 71.43 compared with 67.20
      Canadian dollars in the targeted group. The sensitization rates per RhD-negative
      pregnancy were equal, at 0.0012, for the current and targeted programs.
      Implementing targeted antenatal anti-RhD prophylaxis would save 4072 doses
      (20.1%) of RhIG over a 1-year period in Alberta when compared to the current
      program. CONCLUSIONS: These data support the feasibility of a targeted antenatal
      anti-RhD prophylaxis program, at a lower cost than that of the existing routine
      prophylaxis program, with no increased risk of sensitization.

PMID- 25380025
TI  - Contamination of mercury during the wintering period influences concentrations at
      breeding sites in two migratory piscivorous birds.
AB  - Many aquatic fish-eating birds migrate long distances and are exposed to
      different mercury concentrations ([Hg]) during their annual cycle. Here we
      examined the importance of migration on [Hg] in two colonial migratory fish
      eating bird species. We determined temporal trends of [Hg] and stable isotopes of
      carbon (delta(13)C) and nitrogen (delta(15)N) during the annual cycle in Double
      crested Cormorants (Phalacrocorax auritus) and Caspian Terns (Hydroprogne caspia)
      breeding in Lake Ontario by a repeated sampling of breast feathers and blood from
      recaptured individuals. We found an effect of previous winter [Hg], species, sex,
      and location to explain variations of Hg at breeding sites. This suggests Hg
      carryover from winter to summer periods and that variations of [Hg] in the summer
      are partially explained by [Hg] in the winter. Carryover of Hg among seasons and
      slow changes in [Hg] over time were found especially for individuals in high
      winter exposure groups, suggesting a slow depuration rate and a fast uptake rate
      for both species. In contrast, stable isotope values rapidly switched to reach
      equilibrium at a similar midpoint regardless of winter habitat or diet suggesting
      minimal carryover of isotopic signatures. The potential of Hg carryover from
      wintering sites indicates that Hg concentrations in birds at a given time may be
      influenced by previous exposure from distant locations. 

PMID- 25380026
TI  - Myelofibrosis patients in Belgium: disease characteristics.
AB  - OBJECTIVE: To date, only a small number of epidemiological studies on
      myelofibrosis have been performed. The current study aimed to characterize the
      myelofibrosis patient population in Belgium according to pre-defined disease
      parameters (diagnosis, risk categories, hemoglobin <10 g/dl, spleen size,
      constitutional symptoms, platelet count, myeloblast count), with a view to
      obtaining a deeper understanding of the proportion of patients that may benefit
      from the novel myelofibrosis therapeutic strategies. METHODS: A survey was used
      to collect data on prevalence and disease parameters on all myelofibrosis
      patients seen at each of 18 participating hematologic centers in 2011. Aggregated
      data from all centers were used for analysis. Analyses were descriptive and
      quantitative. RESULTS: A total of 250 patients with myelofibrosis were captured;
      of these, 136 (54%) were male and 153 (61%) were over 65 years old. One hundred
      sixty-five (66%) of myelofibrosis patients had primary myelofibrosis and 85 (34%)
      had secondary myelofibrosis. One hundred ninety-three myelofibrosis patients
      (77%) had a palpable spleen. About a third of patients (34%) suffered from
      constitutional symptoms. Two hundred twenty-two (89%) myelofibrosis patients had
      platelet count ?50 000/MUl and 201 (80%) had platelet count ?100 000/MUl. Of 250
      patients, 85 (34%) had a myeloblast count ?1%. Six (2%) patients had undergone a
      splenectomy. Thirteen (5.2%) patients had undergone radiotherapy for
      splenomegaly. CONCLUSIONS: The results of this survey provide insight into the
      characteristics of the Belgian myelofibrosis population. They also suggest that a
      large proportion of these patients could stand to benefit from the therapies
      currently under development.

PMID- 25380027
TI  - Formulation pre-screening of inhalation powders using computational atom-atom
      systematic search method.
AB  - The synthonic modeling approach provides a molecule-centered understanding of the
      surface properties of crystals. It has been applied extensively to understand
      crystallization processes. This study aimed to investigate the functional
      relevance of synthonic modeling to the formulation of inhalation powders by
      assessing cohesivity of three active pharmaceutical ingredients (APIs,
      fluticasone propionate (FP), budesonide (Bud), and salbutamol base (SB)) and the
      commonly used excipient, alpha-lactose monohydrate (LMH). It is found that FP (
      11.5 kcal/mol) has a higher cohesive strength than Bud (-9.9 kcal/mol) or SB (
      7.8 kcal/mol). The prediction correlated directly to cohesive strength
      measurements using laser diffraction, where the airflow pressure required for
      complete dispersion (CPP) was 3.5, 2.0, and 1.0 bar for FP, Bud, and SB,
      respectively. The highest cohesive strength was predicted for LMH (-15.9
      kcal/mol), which did not correlate with the CPP value of 2.0 bar (i.e., ranking
      lower than FP). High FP-LMH adhesive forces (-11.7 kcal/mol) were predicted.
      However, aerosolization studies revealed that the FP-LMH blends consisted of
      agglomerated FP particles with a large median diameter (~4-5 MUm) that were not
      disrupted by LMH. Modeling of the crystal and surface chemistry of LMH identified
      high electrostatic and H-bond components of its cohesive energy due to the
      presence of water and hydroxyl groups in lactose, unlike the APIs. A direct
      comparison of the predicted and measured cohesive balance of LMH with APIs will
      require a more in-depth understanding of highly hydrogen-bonded systems with
      respect to the synthonic engineering modeling tool, as well as the influence of
      agglomerate structure on surface-surface contact geometry. Overall, this research
      has demonstrated the possible application and relevance of synthonic engineering
      tools for rapid pre-screening in drug formulation and design. 

PMID- 25380028
TI  - Plasmonic properties of regiospecific core-satellite assemblies of gold nanostars
      and nanospheres.
AB  - Solution-based molecularly-mediated bottom-up assembly of gold nanostars and
      nanospheres in regiospecific core-satellite nanoarchitectures is reported. The
      controlled assembly is driven by coupling reactions in solution between small,
      rigid, Raman-active organic molecules bound to the surface of the nanoparticles,
      and leads to much narrower interparticle gaps than achievable with DNA-based
      assembly methods. In the described system, gold nanostars with multiple sharp
      spikes, ideal for electromagnetic field enhancement, are used as the core
      particle onto which spherical satellites are assembled. Transmission electron
      micrographs show that the core-satellite structures assemble with <2 nm
      interparticle gaps and regiospecific binding of only one sphere per spike, and
      the process can be followed by monitoring changes in the surface enhanced Raman
      scattering (SERS) spectra of the Raman active linkers. The assembled structures
      give rise on average to two orders of magnitude SERS signal enhancement per
      nanoparticle in comparison to their constituents, which can be attributed to the
      creation of SERS "hot spots" between the nanostar tip and the satellite sphere.
      Two dimensional finite element electromagnetic models show strongly confined
      electromagnetic field intensity in the narrow interparticle gaps of core
      satellite assemblies, which is significantly enhanced in comparison to the
      constituent nanoparticles, thus corroborating the experimental findings. Thus,
      the assemblies reported here can be envisioned as SERS-tags for imaging purposes
      as well as a model system for SERS-based chemical sensing with improved
      sensitivity. 

PMID- 25380029
TI  - A two-dimensional hybrid with molybdenum disulfide nanocrystals strongly coupled
      on nitrogen-enriched graphene via mild temperature pyrolysis for high performance
      lithium storage.
AB  - A novel 2D hybrid with MoS(2) nanocrystals strongly coupled on nitrogen-enriched
      graphene (MoS(2)/NG(g-C(3)N(4))) is realized by mild temperature pyrolysis (550 
      degrees C) of a self-assembled precursor (MoS(3)/g-C(3)N(4)-H(+)/GO). With rich
      active sites, the boosted electronic conductivity and the coupled structure,
      MoS(2)/NG(g-C(3)N(4)) achieves superior lithium storage performance.

PMID- 25380030
TI  - CoMoO4 nanoparticles anchored on reduced graphene oxide nanocomposites as anodes
      for long-life lithium-ion batteries.
AB  - A self-assembled CoMoO4 nanoparticles/reduced graphene oxide (CoMoO4NP/rGO), was
      prepared by a hydrothermal method to grow 3-5 nm sized CoMoO4 particles on
      reduced graphene oxide sheets and used as an anode material for lithium-ion
      batteries. The specific capacity of CoMoO4NP/rGO anode can reach up to 920 mAh g(
      1) at a current rate of 74 mA g(-1) in the voltage range between 3.0 and 0.001 V,
      which is close to the theoretical capacity of CoMoO4 (980 mAh g(-1)). The
      fabricated half cells also show good rate capability and impressive cycling
      stability with 8.7% capacity loss after 600 cycles under a high current density
      of 740 mA g(-1). The superior electrochemical performance of the synthesized
      CoMoO4NP/rGO is attributed to the synergetic chemical coupling effects between
      the conductive graphene networks and the high lithium-ion storage capability of
      CoMoO4 nanoparticles. 

PMID- 25380031
TI  - Rim-functionalized cryptophane-111 derivatives via heterocapping, and their xenon
      complexes.
AB  - Capping of cyclotriphenolene (3a) by the more available cyclotriguaiacylene (3c)
      or trisbromocyclotriphenolene (3b) gives the first rim-functionalized cryptophane
      111 derivatives. Crystal structures of the xenon complexes reveal high cavity
      packing coefficients and unprecedentedly short Xe...C contacts.

PMID- 25380032
TI  - A case report of transverse testicular ectopia with testicular microlithiasis.
AB  - Transverse testicular ectopia is a rare congenital anomaly in which both testes
      migrate along the same inguinal canal toward the scrotum. This report describes
      the case of the rarest form of transverse testicular ectopia in a 23-year-old man
      with coexisting testicular microlithiasis in one of the two testes as diagnosed
      on sonography and confirmed on MRI. We are unaware of any previous published
      reports of this association. Although the etiology of both conditions is
      debatable, each is believed to be associated with an increased risk of testicular
      malignancy, and this poses a dilemma for the future management of this patient.

PMID- 25380033
TI  - Provider contribution to an episiotomy risk model.
AB  - OBJECTIVE: The extent to which the observed variation in episiotomy rates can be
      attributed to individual practitioners is not known. We sought to analyze the
      contribution of the attending midwife to a risk model for episiotomy. STUDY
      DESIGN: We prospectively collected data on 736 consecutive vaginal deliveries in
      nulliparas at a tertiary maternity hospital. The study measures the impact of the
      attending midwife on the decision to perform an episiotomy, controlling for a
      host of patient and clinical characteristics. Midwife effect is evaluated in
      terms of its overall contribution to the explanatory power of logistic regression
      model. RESULTS: The overall rate of episiotomy in primiparas was 40.6%.
      Individual midwife episiotomy rate ranged from 5.6% to 73.9% (p < 0.0001). After
      controlling for confounding factors with logistic regression, maternal age >=35
      years (OR 1.61, 95%CI: 1.02-2.52), vacuum extraction (OR 26.88, 95%CI: 2.57
      280.7), fundal pressure (OR 62.90, 95%CI: 18.39-214.98), second-stage duration
      (OR 2.24, 95%CI: 1.53-3.28), and the individual midwife were all associated with
      episiotomy use. The midwife attending the birth and fundal pressure provided the
      greatest explanatory power of the model. CONCLUSIONS: The attending provider adds
      a significant independent effect to the episiotomy risk model. This has
      implications for both practice and research in this clinical area.

PMID- 25380035
TI  - Exploitation of sperm-Escherichia coli interaction at the receptor-ligand level
      for the development of anti-receptor antibodies as the vaginal contraceptive.
AB  - In an earlier work performed in our laboratory, we have been able to isolate a
      sperm receptor (SR) from human spermatozoa playing critical role in fertilization
      using sperm--E. coli interactions at the receptor-ligand level. It has been
      hypothesized that for the development of an immunocontraceptive, antibodies
      generated against the SR should have the ability to impair sperm parameters. In
      this league, an attempt was made to generate anti-SR antibodies and their effect
      on sperm parameters such as motility, viability, Mg(2+) -dependent ATPase
      activity, acrosome status, and apoptotic index was examined. Loss of sperm
      motility was observed with 100% agglutination. Interaction of anti-SR antibodies
      with spermatozoa resulted in reduced Mg(2+) -dependent ATPase activity (1020 +/-
      0.53%), premature acrosomal loss (61.5 +/- 0.67%) as well as induced apoptosis
      (58.76 +/- 2.5%). The induction of sperm damage was specifically because of anti
      SR polyclonal antibodies as it could be mitigated by the addition of purified SR.
      Further, when in vivo efficacy of anti-SR antibodies was checked, results showed
      that a single intravaginal administration with anti-SR antibodies in female
      BALB/c mice led to the failure of conception. However, simultaneous
      administration of SR with anti-SR polyclonal antibodies resulted in sustenance of
      fertility. Infertility induced by anti-SR antibodies did not show any other
      tissue pathology; hence the present work highlights the potential of anti-SR
      polyclonal antibodies to be used as a vaginal contraceptive.

PMID- 25380034
TI  - Modulation of tumorigenesis by dietary intervention is not mediated by SIRT1
      catalytic activity.
AB  - The protein deacetylase SIRT1 is involved in the regulation of a large number of
      cellular processes that are thought to be required for cancer initiation and
      progression. Both SIRT1 activity and tumorigenesis can be influenced by dietary
      fat and polyphenolics. We set out to determine whether dietary modulations of
      tumorigenesis are mediated by SIRT1 catalytic functions. We introduced a mammary
      gland tumor-inducing transgene, MMTV-PyMT, into stocks of mice bearing a H355Y
      point mutation in the Sirt1 gene that abolishes SIRT1 catalytic activity. Tumor
      latency was reduced in animals fed a high fat diet but this effect was not
      dependent on SIRT1 activity. Resveratrol had little effect on tumor formation
      except in animals heterozygous for the mutant Sirt1 gene. We conclude that the
      effects of these dietary interventions on tumorigenesis are not mediated by
      modulation of SIRT1 catalytic activity. 

PMID- 25380036
TI  - Alanine scanning of cucumber mosaic virus (CMV) 2b protein identifies different
      positions for cell-to-cell movement and gene silencing suppressor activity.
AB  - The multifunctional 2b protein of CMV has a role in the long distance and local
      movement of the virus, in symptom formation, in evasion of defense mediated by
      salicylic acid as well as in suppression of RNA silencing. The role of conserved
      amino acid sequence domains were analyzed previously in the protein function, but
      comprehensive analysis of this protein was not carried out until recently. We
      have analyzed all over the 2b protein by alanine scanning mutagenesis changing
      three consecutive amino acids (aa) to alanine. We have identified eight aa
      triplets as key determinants of the 2b protein function in virus infection. Four
      of them (KKQ/22-24/AAA, QNR/31-33/AAA, RER/34-36/AAA, SPS/40-42/AAA) overlap with
      previously determined regions indispensable in gene silencing suppressor
      function. We have identified two additional triplets necessary for the suppressor
      function of the 2b protein (LPF/55-57/AAA, NVE/10-12/AAA), and two other
      positions were required for cell-to-cell movement of the virus (MEL/1-3/AAA,
      RHV/70-72/AAA), which are not essential for suppressor activity. 

PMID- 25380038
TI  - Impaired executive functions in paediatric obsessive-compulsive disorder
      patients.

PMID- 25380039
TI  - Olanzapine plus fluoxetine treatment alters mitochondrial respiratory chain
      activity in the rat brain.

PMID- 25380037
TI  - The Drosophila midkine/pleiotrophin homologues Miple1 and Miple2 affect adult
      lifespan but are dispensable for alk signaling during embryonic gut formation.
AB  - Midkine (MDK) and Pleiotrophin (PTN) are small heparin-binding cytokines with
      closely related structures. The Drosophila genome harbours two genes encoding
      members of the MDK/PTN family of proteins, known as miple1 and miple2. We have
      investigated the role of Miple proteins in vivo, in particular with regard to
      their proposed role as ligands for the Alk receptor tyrosine kinase (RTK). Here
      we show that Miple proteins are neither required to drive Alk signaling during
      Drosophila embryogenesis, nor are they essential for development in the fruit
      fly. Additionally we show that neither MDK nor PTN can activate hALK in vivo when
      ectopically co-expressed in the fly. In conclusion, our data suggest that Alk is
      not activated by MDK/PTN related growth factors Miple1 and Miple 2 in vivo. 

PMID- 25380040
TI  - Long-term depression is a stroke risk factor.

PMID- 25380041
TI  - Impact of neuropsychiatry screening in neurological in-patients: comparison with
      routine clinical practice.

PMID- 25380042
TI  - Perspective taking in Korsakoff's syndrome: the role of executive functioning and
      task complexity.

PMID- 25380043
TI  - Determinants of irritability in Huntington's disease.

PMID- 25380044
TI  - Abnormal gait and bradykinesia in the preclinical phase of Huntington's disease -
      psychogenic movement disorder?.

PMID- 25380045
TI  - Hydroxychloroquine-induced acute psychosis in a systemic lupus erythematosus
      female.

PMID- 25380047
TI  - Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent
      multivesicular body biogenesis.
AB  - Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton
      and membrane organization, cell division and host/pathogen interactions. The
      precise function of many family members remains elusive. We show that SEPT6 and
      SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular
      body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting
      cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3
      membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP
      interactions also influence the membrane interaction of ESCRT (endosomal-sorting
      complex required for transport)-I, which selects ubiquitinated cargos for
      degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7
      function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane
      domains, they uncover an unsuspected coordination of these sorting machineries
      during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3
      interactor regulating ESCRT-I sorting activity and whose mutations are linked
      with Charcot-Marie-Tooth neuropathies. 

PMID- 25380049
TI  - Synthesis and SHG properties of two new cyanurates: Sr3(O3C3N3)2 (SCY) and
      Eu3(O3C3N3)2 (ECY).
AB  - The new cyanurates Sr3(O3C3N3)2 (SCY) and Eu3(O3C3N3)2 (ECY) were prepared via
      exothermic solid state metathesis reactions from MCl2 (M = Sr, Eu) and K(OCN) in
      silica tubes at 525  degrees C. Both structures were characterized by means of
      powder and single crystal X-ray diffraction, and their structures are shown to
      crystallize with the noncentrosymmetric space group R3c (No. 161). Infrared
      spectra and nonlinear optical properties (NLO) of SCY and ECY are reported in
      comparison to those of CCY and beta-BaB2O4 (beta-BBO). 

PMID- 25380048
TI  - Natural variants of C. elegans demonstrate defects in both sperm function and
      oogenesis at elevated temperatures.
AB  - The temperature sensitivity of the germ line is conserved from nematodes to
      mammals. Previous studies in C. briggsae and Drosophila showed that isolates
      originating from temperate latitudes lose fertility at a lower temperature than
      strains originating from tropical latitudes. In order to investigate these
      relationships in C. elegans, analysis of the fertility of 22 different wild-type
      isolates of C. elegans isolated from equatorial, tropical and temperate regions
      was undertaken. It was found that there are significant temperature, genotype and
      temperature * genotype effects on fertility but region of isolation showed no
      significant effect on differences in fertility. For most isolates 100% of the
      population maintained fertility from 20 degrees C to 26 degrees C, but there was
      a precipitous drop in the percentage of fertile hermaphrodites at 27 degrees C.
      In contrast, all isolates show a progressive decrease in brood size as
      temperature increases from 20 degrees C to 26 degrees C, followed by a brood size
      near zero at 27 degrees C. Temperature shift experiments were performed to better
      understand the causes of high temperature loss of fertility. Males up-shifted to
      high temperature maintained fertility, while males raised at high temperature
      lost fertility. Down-shifting males raised at high temperature generally did not
      restore fertility. This result differs from that observed in Drosophila and
      suggested that in C. elegans spermatogenesis or sperm function is irreversibly
      impaired in males that develop at high temperature. Mating and down-shifting
      experiments with hermaphrodites were performed to investigate the relative
      contributions of spermatogenic and oogenic defects to high temperature loss of
      fertility. It was found that the hermaphrodites of all isolates demonstrated loss
      in both spermatogenic and oogenic germ lines that differed in their relative
      contribution by isolate. These studies uncovered unexpectedly high variation in
      both the loss of fertility and problems with oocyte function in natural variants
      of C. elegans at high temperature. 

PMID- 25380051
TI  - Rationale and study design of the RESERVOIR trial: a randomized trial comparing
      reservoir-based polymer-free amphilimus-eluting stents versus everolimus-eluting
      stents with durable polymer in patients with diabetes mellitus.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) remain at high risk for stent
      restenosis and adverse cardiovascular events in the drug-eluting stent era. The
      amphilimus-eluting stent (AES) is a third generation reservoir-based polymer-free
      drug-eluting stent that has shown promising preliminary results in patients with
      DM. It has been suggested that the formulation of the drug with fatty acids could
      not only modulate the drug release in a timely manner but also achieve convenient
      levels of drug concentration in diabetic cardiac cells. The aim of this trial is
      to assess the efficacy of the AES in patients with DM compared with the cobalt
      chromium everolimus-eluting stent with non-erodible polymer (EES). STUDY DESIGN:
      This is an investigator-initiated, multicenter, randomized clinical trial,
      performed in patients with DM. A total of 112 diabetic patients receiving glucose
      lowering agents and requiring percutaneous revascularization of a de novo lesion
      will be randomized in a 1:1 fashion to receive AES or EES. The primary endpoint
      is the neointimal volume obstruction at 9 months, evaluated by optical coherence
      tomography. Secondary endpoints will include strut coverage, angiographic in
      stent late loss and clinical endpoints such as target vessel revascularization or
      probable/definite stent thrombosis. This study completed the inclusion in October
      2013. CONCLUSIONS: The RESERVOIR trial is an investigator-initiated trial that
      will evaluate whether the polymer-free AES is not inferior to the EES inhibiting
      the neointimal hyperplasia in patients with DM. These results are also expected
      to improve our knowledge of the neointimal healing process in this population
      (Clinicaltrials.gov number NCT01710748).

PMID- 25380050
TI  - Differential effect of HDAC3 on cytoplasmic and nuclear huntingtin aggregates.
AB  - Histone deacetylases (HDACs) are potential therapeutic targets of polyglutamine
      (pQ) diseases including Huntington's disease (HD) that may function to correct
      aberrant transcriptional deactivation caused by mutant pQ proteins. HDAC3 is a
      unique class 1 HDAC found in both the cytoplasm and in the nucleus. However, the
      precise functions of HDAC3 in the two cellular compartments are only vaguely
      known. HDAC3 directly binds to huntingtin (Htt) with short pQ and this
      interaction is important for suppressing neurotoxicity induced by HDAC3. With
      long pQ Htt, the interaction with HDAC3 is inhibited, and this supposedly
      promotes neuronal death, indicating that HDAC3 would be a good therapeutic target
      for HD. However, the knockout of one HDAC3 allele did not show any efficacy in
      reducing neurodegenerative symptoms in a mouse model of HD. Therefore, the role
      of HDAC3 in the pathogenesis of HD has yet to be fully elucidated. We attempted
      to resolve this issue by focusing on the different roles of HDAC3 on cytoplasmic
      and nuclear Htt aggregates. In addition to supporting the previous findings, we
      found that HDAC3 preferentially binds to nuclear Htt over cytoplasmic ones.
      Specific HDAC3 inhibitors increased the total amount of Htt aggregates by
      increasing the amount of nuclear aggregates. Both cytoplasmic and nuclear Htt
      aggregates were able to suppress endogenous HDAC3 activity, which led to
      decreased nuclear proteasome activity. Therefore, we concluded that Htt
      aggregates impair nuclear proteasome activity through the inhibition of HDAC3.
      Our findings provide new insights regarding cross-compartment proteasome
      regulation.

PMID- 25380052
TI  - Expression profiling of rectal tumors defines response to neoadjuvant treatment
      related genes.
AB  - To date, no effective method exists that predicts the response to preoperative
      chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless,
      identification of patients who have a higher likelihood of responding to
      preoperative CRT could be crucial in decreasing treatment morbidity and avoiding
      expensive and time-consuming treatments. The aim of this study was to identify
      signatures or molecular markers related to response to pre-operative CRT in LARC.
      We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10
      responders and 16 non-responders) without metastasis using Human WG CodeLink
      microarray platform. Two hundred and fifty seven genes were differentially over
      expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed
      a significant ratio of differentially expressed genes related to cancer, cellular
      growth and proliferation pathways, and c-Myc network. We demonstrated that high
      Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic
      factor for response to treatment in LARC patients (p<0.05). Using this gene set,
      we were able to establish a new model for predicting the response to CRT in
      rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect
      the value of gene expression profiling to gain insight about the molecular
      pathways involved in the response to treatment of LARC patients. These findings
      could be clinically relevant and support the use of mRNA levels when aiming to
      identify patients who respond to CRT therapy. 

PMID- 25380054
TI  - Relationship Between Intraocular Pressure and Parameters of Obesity in Korean
      Adults: The 2008-2010 Korea National Health and Nutrition Examination Survey.
AB  - PURPOSE: To examine the associations of various parameters of obesity including
      adiposity with intraocular pressure (IOP) using nationally representative data of
      South Korean adults. MATERIAL AND METHODS: This cross-sectional study analyzed
      the data from the 2008-2010 Korea National Health and Nutrition Examination
      Survey. A total of 15,271 subjects (6600 men and 8671 women) participated. Body
      mass index (BMI), waist circumference (WC), total body fat mass, and total and
      regional body fat percentage were measured as parameters of obesity. RESULTS: IOP
      showed positive linear associations with BMI, WC, total fat mass, and total and
      regional body fat percentages in men, and with BMI, WC, total fat mass, and trunk
      fat percentage in women after adjusting for confounding variables. Men with
      higher BMI, WC, total fat mass, and total and regional body fat percentages
      exhibited increasing trends in odd ratios for having IOP >= 18 mmHg after
      adjusting for all confounding factors (p for trend <0.001 for BMI and total fat
      mass; p for trend = 0.038 for WC; 0.003 for total body fat percentage; 0.002 for
      trunk fat percentage; 0.004 for leg fat percentage). However, only BMI showed a
      significantly increasing trend in the risk of IOP >=18 mmHg in women.
      CONCLUSIONS: In addition to BMI, WC and total fat mass, total and regional body
      fat percentage in men and trunk fat percentage in women are positively associated
      with IOP. Increased BMI, WC, and total and regional body fat are positively
      associated with a risk of higher IOP (IOP >=18 mmHg), especially in Korean men.

PMID- 25380053
TI  - The molecular epidemiological characteristics and genetic diversity of salmonella
      typhimurium in Guangdong, China, 2007-2011.
AB  - BACKGROUND: Salmonella enterica serovar Typhimurium is the most important serovar
      associated with human salmonellosis worldwide. Here we aimed to explore the
      molecular epidemiology and genetic characteristics of this serovar in Guangdong,
      China. METHODOLOGY: We evaluated the molecular epidemiology and genetic
      characteristics of 294 endemic Salmonella Typhimurium clinical isolates which
      were collected from 1977 to 2011 in Guangdong, China, and compared them with a
      global set of isolates of this serovar using epidemiological data and Multilocus
      Sequence Typing (MLST) analysis. PRINCIPAL FINDING: The 294 isolates were
      assigned to 13 Sequencing types (STs) by MLST, of which ST34 and ST19 were the
      most common in Guangdong. All the STs were further assigned to two eBurst Groups,
      eBG1 and eBG138. The eBG1 was the major group endemic in Guangdong. Nucleotide
      and amino acid variability were comparable for all seven MLST loci. Tajima's D
      test suggested positive selection in hisD and thrA genes (p<0.01), but positive
      selection was rejected for the five other genes (p>0.05). In addition, The
      Tajima's D test within each eBG using the global set of isolates showed positive
      selection in eBG1 and eBG138 (p<0.05), but was rejected in eBG243 (p>0.05). We
      also analyzed the phylogenetic structure of Salmonella Typhimurium from worldwide
      sources and found that certain STs are geographically restricted. ACSSuT was the
      predominant multidrug resistance pattern for this serovar. The resistant profiles
      ACSSuTTmNaG, ACSSuTTmNa and ACSuTTmNaG seem to be specific for ST34, and ASSuTNa
      for ST19. CONCLUSION: Here we presented a genotypic characterization of
      Salmonella Typhimurium isolates using MLST and found two major STs are endemic in
      Guangdong. Our analyses indicate that genetic selection may have shaped the
      Salmonella Typhimurium populations. However, further evaluation with additional
      isolates from various sources will be essential to reveal the scope of the
      epidemiological characteristics of Salmonella Typhimurium in Guangdong, China.

PMID- 25380055
TI  - Novel roles for p53 in the genesis and targeting of tetraploid cancer cells.
AB  - Tetraploid (4N) cells are considered important in cancer because they can display
      increased tumorigenicity, resistance to conventional therapies, and are believed
      to be precursors to whole chromosome aneuploidy. It is therefore important to
      determine how tetraploid cancer cells arise, and how to target them. P53 is a
      tumor suppressor protein and key regulator of tetraploidy. As part of the
      "tetraploidy checkpoint", p53 inhibits tetraploid cell proliferation by promoting
      a G1-arrest in incipient tetraploid cells (referred to as a tetraploid G1
      arrest). Nutlin-3a is a preclinical drug that stabilizes p53 by blocking the
      interaction between p53 and MDM2. In the current study, Nutlin-3a promoted a p53
      dependent tetraploid G1 arrest in two diploid clones of the HCT116 colon cancer
      cell line. Both clones underwent endoreduplication after Nutlin removal, giving
      rise to stable tetraploid clones that showed increased resistance to ionizing
      radiation (IR) and cisplatin (CP)-induced apoptosis compared to their diploid
      precursors. These findings demonstrate that transient p53 activation by Nutlin
      can promote tetraploid cell formation from diploid precursors, and the resulting
      tetraploid cells are therapy (IR/CP) resistant. Importantly, the tetraploid
      clones selected after Nutlin treatment expressed approximately twice as much P53
      and MDM2 mRNA as diploid precursors, expressed approximately twice as many p53
      MDM2 protein complexes (by co-immunoprecipitation), and were more susceptible to
      p53-dependent apoptosis and growth arrest induced by Nutlin. Based on these
      findings, we propose that p53 plays novel roles in both the formation and
      targeting of tetraploid cells. Specifically, we propose that 1) transient p53
      activation can promote a tetraploid-G1 arrest and, as a result, may inadvertently
      promote formation of therapy-resistant tetraploid cells, and 2) therapy-resistant
      tetraploid cells, by virtue of having higher P53 gene copy number and expressing
      twice as many p53-MDM2 complexes, are more sensitive to apoptosis and/or growth
      arrest by anti-cancer MDM2 antagonists (e.g. Nutlin). 

PMID- 25380057
TI  - Ultrathin cobalt-manganese layered double hydroxide is an efficient oxygen
      evolution catalyst.
AB  - Cost-effective production of solar fuels requires robust and earth-abundant
      oxygen evolution reaction (OER) catalysts. Herein, we report that ultrathin
      nanoplates of cobalt-manganese layered double hydroxide (CoMn LDH) are a highly
      active and stable oxygen evolution catalyst. The catalyst was fabricated by a one
      pot coprecipitation method at room temperature, and its turnover frequency (TOF)
      is more than 20 times higher than the TOFs of Co and Mn oxides and hydroxides,
      and 9 times higher than the TOF of a precious IrO2 catalyst. The activity of the
      catalyst was promoted by anodic conditioning, which was proposed to form
      amorphous regions and reactive Co(IV) species on the surface. The stability of
      the catalyst was demonstrated by continued electrolysis. 

PMID- 25380056
TI  - Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in
      the blood plasma of children.
AB  - BACKGROUND: The diagnosis of autism spectrum disorder (ASD) at the earliest age
      possible is important for initiating optimally effective intervention. In the
      United States the average age of diagnosis is 4 years. Identifying metabolic
      biomarker signatures of ASD from blood samples offers an opportunity for
      development of diagnostic tests for detection of ASD at an early age. OBJECTIVES:
      To discover metabolic features present in plasma samples that can discriminate
      children with ASD from typically developing (TD) children. The ultimate goal is
      to identify and develop blood-based ASD biomarkers that can be validated in
      larger clinical trials and deployed to guide individualized therapy and
      treatment. METHODS: Blood plasma was obtained from children aged 4 to 6, 52 with
      ASD and 30 age-matched TD children. Samples were analyzed using 5 mass
      spectrometry-based methods designed to orthogonally measure a broad range of
      metabolites. Univariate, multivariate and machine learning methods were used to
      develop models to rank the importance of features that could distinguish ASD from
      TD. RESULTS: A set of 179 statistically significant features resulting from
      univariate analysis were used for multivariate modeling. Subsets of these
      features properly classified the ASD and TD samples in the 61-sample training set
      with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an
      independent 21-sample validation set. CONCLUSIONS: This analysis of blood plasma
      metabolites resulted in the discovery of biomarkers that may be valuable in the
      diagnosis of young children with ASD. The results will form the basis for
      additional discovery and validation research for 1) determining biomarkers to
      develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2)
      gaining new insight into the biochemical mechanisms of various subtypes of ASD 3)
      identifying biomolecular targets for new modes of therapy, and 4) providing the
      basis for individualized treatment recommendations.

PMID- 25380058
TI  - Ventilatory and sensory responses in adult survivors of preterm birth and
      bronchopulmonary dysplasia with reduced exercise capacity.
AB  - RATIONALE: Adults born very to extremely preterm, with or without
      bronchopulmonary dysplasia (BPD), have obstructive lung disease, but it is
      unknown whether this results in respiratory limitations, such as mechanical
      constraints to Vt expansion during exercise leading to intolerable dyspnea and
      reduced exercise tolerance, as it does in patients with chronic obstructive
      pulmonary disease. OBJECTIVES: To test the hypothesis that adult survivors of
      preterm birth (<=32 wk gestational age) with (n = 20) and without BPD (n = 15)
      with reduced exercise capacity demonstrate clinically important respiratory
      limitations at near-maximal exercise compared with full-term control subjects (n
      = 20). METHODS: Detailed ventilatory and sensory measurements were made before
      and during exercise on all patients in the three study groups. MEASUREMENTS AND
      MAIN RESULTS: During exercise at 90% of peak [Formula: see text]o2 ([Formula: see
      text]o2peak), inspiratory reserve volume decreased to ~0.5 L in all groups, but
      this occurred at significantly lower absolute workloads and [Formula: see text]e
      in ex-preterm subjects with and without BPD compared with full-term control
      subjects. Severe dyspnea was present and similar at comparable [Formula: see
      text]e between all groups, but leg discomfort at comparable workloads was greater
      in ex-preterm subjects with and without BPD compared with control subjects. At 50
      to 90% of [Formula: see text]o2peak, exercise-induced expiratory flow limitation
      was significantly greater in ex-preterm subjects with BPD compared with ex
      preterm subjects without BPD and control subjects. The degree of expiratory flow
      limitation in ex-preterm subjects with and without BPD was significantly related
      to neonatal O2 therapy duration. CONCLUSIONS: Severe dyspnea and leg discomfort
      associated with critical constraints on Vt expansion may lead to reduced exercise
      tolerance in adults born very or extremely preterm, whether or not their birth
      was complicated by BPD and despite differences in expiratory flow limitation. In
      this regard, adults born very or extremely preterm have respiratory limitations
      to exercise similar to patients with chronic obstructive pulmonary disease.

PMID- 25380059
TI  - Neurocognitive profiles of marginally housed persons with comorbid substance
      dependence, viral infection, and psychiatric illness.
AB  - INTRODUCTION: Individuals living in single-room occupancy (SRO) hotels constitute
      a socially marginalized group with exposure to multiple factors with adverse
      effects on neurocognition, including substance use, viral infection, psychiatric
      illness, and brain injury. Consequently, marked heterogeneity in neurocognitive
      functioning is observed. This study aimed to identify and describe distinct
      neurocognitive profiles within a marginally housed sample. METHOD: Two hundred
      and forty-nine (N = 249) SRO hotel residents (mean age = 43.5 years) were
      recruited. A battery of tests assessed neurocognition across six domains:
      premorbid IQ, verbal memory, attention, inhibition, mental flexibility, and
      decision making. Clinical examinations collected information pertaining to
      substance use and psychiatric diagnoses, viral infection, psychiatric symptoms,
      risk behaviors, and everyday functioning. Cluster analysis was used to identify
      subgroups of individuals with similar neurocognitive profiles and was
      supplemented with a discriminant function analysis. Analyses of variance and chi
      square tests were used to validate the derived clusters on key clinical and
      functional variables. RESULTS: A three-cluster solution was found to be optimal.
      Cluster 1 (n = 59) presented as overall higher functioning, whereas Cluster 3 (n
      = 87) exhibited overall lower functioning with a relative strength in decision
      making skills. Cluster 2 (n = 103) was characterized by neurocognitive abilities
      that generally bisected the performance of the other groups, but with a relative
      weakness in decision-making skills. Discriminant function analysis indicated the
      six neurocognitive variables comprised two underlying dimensions that accounted
      for between-group variance. Clusters meaningfully differed on demographics,
      substance use, viral exposure, psychiatric symptoms, neurological soft signs, and
      risk behavior. CONCLUSION: Neurocognitive functioning provides the basis for
      identifying meaningful subgroups of marginally housed individuals, which can be
      reliably differentiated on key variables. This approach facilitates an
      understanding of the neurocognitive dysfunction and associated vulnerabilities of
      marginalized persons and ultimately may elucidate intervention targets.

PMID- 25380060
TI  - Physicochemical analysis of structural alteration and advanced glycation end
      products generation during glycation of H2A histone by 3-deoxyglucosone.
AB  - Advanced glycation end-products comprise a complex and heterogeneous group of
      compounds that have been implicated in diabetes-related complications. The
      importance of the Maillard reaction is depicted by the formation of reactive
      intermediate products known as alpha-oxoaldehydes, such as 3-deoxyglucosone (3
      DG). This product has been found to be involved in accelerated vascular damage in
      diabetes. In the present study, calf thymus histone H2A was reacted with 3-DG,
      and the generation of advanced glycation end products was investigated by
      determining the degree of side chain modifications (lysine and arginine
      residues), Amadori products, carbonyl content, N(epsilon) -carboxymethyl lysine,
      and pentosidine using various physicochemical techniques. Moreover, fluorescence,
      absorbance as well as structural characteristics of glycated-H2A were
      comprehensively investigated. Overall, this study demonstrates structural
      perturbation, formation of different intermediates, and AGEs that are believed to
      hamper the normal functioning of H2A histone, compromising the integrity of
      chromatin structures and function in secondary complications of diabetes.

PMID- 25380062
TI  - Subwavelength lattice optics by evolutionary design.
AB  - This paper describes a new class of structured optical materials--lattice opto
      materials--that can manipulate the flow of visible light into a wide range of
      three-dimensional profiles using evolutionary design principles. Lattice opto
      materials are based on the discretization of a surface into a two-dimensional
      (2D) subwavelength lattice whose individual lattice sites can be controlled to
      achieve a programmed optical response. To access a desired optical property, we
      designed a lattice evolutionary algorithm that includes and optimizes
      contributions from every element in the lattice. Lattice opto-materials can
      exhibit simple properties, such as on- and off-axis focusing, and can also
      concentrate light into multiple, discrete spots. We expanded the unit cell shapes
      of the lattice to achieve distinct, polarization-dependent optical responses from
      the same 2D patterned substrate. Finally, these lattice opto-materials can also
      be combined into architectures that resemble a new type of compound flat lens.

PMID- 25380063
TI  - Adaptation in the visual cortex: influence of membrane trajectory and neuronal
      firing pattern on slow afterpotentials.
AB  - The input/output relationship in primary visual cortex neurons is influenced by
      the history of the preceding activity. To understand the impact that membrane
      potential trajectory and firing pattern has on the activation of slow
      conductances in cortical neurons we compared the afterpotentials that followed
      responses to different stimuli evoking similar numbers of action potentials. In
      particular, we compared afterpotentials following the intracellular injection of
      either square or sinusoidal currents lasting 20 seconds. Both stimuli were
      intracellular surrogates of different neuronal responses to prolonged visual
      stimulation. Recordings from 99 neurons in slices of visual cortex revealed that
      for stimuli evoking an equivalent number of spikes, sinusoidal current injection
      activated a slow afterhyperpolarization of significantly larger amplitude (8.5 +/
      3.3 mV) and duration (33 +/- 17 s) than that evoked by a square pulse (6.4 +/-
      3.7 mV, 28 +/- 17 s; p<0.05). Spike frequency adaptation had a faster time course
      and was larger during plateau (square pulse) than during intermittent
      (sinusoidal) depolarizations. Similar results were obtained in 17 neurons
      intracellularly recorded from the visual cortex in vivo. The differences in the
      afterpotentials evoked with both protocols were abolished by removing calcium
      from the extracellular medium or by application of the L-type calcium channel
      blocker nifedipine, suggesting that the activation of a calcium-dependent current
      is at the base of this afterpotential difference. These findings suggest that not
      only the spikes, but the membrane potential values and firing patterns evoked by
      a particular stimulation protocol determine the responses to any subsequent
      incoming input in a time window that spans for tens of seconds to even minutes.

PMID- 25380064
TI  - A 40-year-old woman with difficulty going down stairs in high-heeled shoes.

PMID- 25380065
TI  - The tumor suppressor rpl36 restrains KRAS(G12V)-induced pancreatic cancer.
AB  - Ribosomal proteins are known to be required for proper assembly of mature
      ribosomes. Recent studies indicate an additional role for ribosomal proteins as
      candidate tumor suppressor genes. Pancreatic acinar cells, recently identified as
      effective cells of origin for pancreatic adenocarcinoma, display especially high
      level expression of multiple ribosomal proteins. We, therefore, functionally
      interrogated the ability of two ribosomal proteins, rpl36 and rpl23a, to alter
      the response to oncogenic Kras in pancreatic acinar cells using a newly
      established model of zebrafish pancreatic cancer. These studies reveal that
      rpl36, but not rpl23a, acts as a haploinsufficient tumor suppressor, as
      manifested by more rapid tumor progression and decreased survival in
      rpl36(hi1807/+);ptf1a:gal4VP16(Tg);UAS:GFP-KRAS(G12V) fish compared with their
      rpl36(+/+);ptf1a:gal4VP16;UAS:GFP-KRAS(G12V) siblings. These results suggest that
      rpl36 may function as an effective tumor suppressor during pancreatic
      tumorigenesis.

PMID- 25380066
TI  - Colocalization of pseudodrusen and subretinal drusenoid deposits using high
      density en face spectral domain optical coherence tomography.
AB  - PURPOSE: To determine if pseudodrusen seen in fundus photography, particularly
      infrared scanning laser ophthalmoscopy, colocalize with subretinal drusenoid
      deposits imaged by optical coherence tomography. METHODS: The patients were
      scanned with spectral domain optical coherence tomography having an A-scan
      spacing of 5.9 MUm and a B-scan spacing of 11 MUm. En face slabs were derived
      from this data set at distances 50 MUm to 90 MUm above the Bruch membrane
      reference plane to image the subretinal drusenoid deposit and also 6 MUm below
      Bruch membrane to image the level of the choriocapillaris. The corresponding
      infrared scanning laser ophthalmoscopy image was registered to the optical
      coherence tomography data by aligning the retinal blood vessels in each imaging
      modality through elastic warping. RESULTS: All ten eyes of nine consecutively
      imaged patients showed a concordance between the pseudodrusen and the subretinal
      drusenoid deposit in every case. At their more internal aspects, subretinal
      drusenoid deposits were generally isolated foci of reflectivity and with
      decreasing distances above the reference plane appeared to become broader,
      reaching confluence with neighboring deposits analogous to a topographical map of
      mountains. In contrast to previous reports based on optical coherence tomography,
      and in keeping with histologic evaluation, no patient was seen to have widespread
      abnormalities in choriocapillaris imaging. CONCLUSION: This study, using an
      unprecedented scan density, showed that pseudodrusen appearance can be attributed
      to subretinal drusenoid deposits. The results of this study have widespread
      applicability in the understanding of age-related macular degeneration and the
      associations of the lesions with other structures in the outer retinal
      neurovascular unit.

PMID- 25380067
TI  - Correspondence.

PMID- 25380068
TI  - Correspondence.

PMID- 25380069
TI  - Retinal injury after inadvertent handheld laser exposure.
AB  - PURPOSE: To evaluate acute and long-term clinical and spectral domain optical
      coherence tomography features after handheld laser exposure to the retina.
      METHODS: Retrospective case series of three children with retinal injury
      secondary to inadvertent handheld laser exposure. All individuals underwent
      ophthalmologic examination and spectral domain optical coherence tomography at
      presentation and follow-up 11 months to 18 months after exposure. RESULTS: Three
      male children aged 6 years to 10 years sustained bilateral macular injury after
      exposure to a handheld green or red laser. Two of the three handheld lasers were
      ordered from foreign internet retailers and were labeled as Class 3B devices.
      Acutely, flat yellow deep retinal lesions with pigment irregularity were
      apparent. Spectral domain optical coherence tomography demonstrated disruption of
      the external limiting membrane and outer photoreceptors, a hyperreflective mound
      extending from the external limiting membrane to the retinal pigment epithelium,
      and linear opacification in Henle's layer. Over time, there was partial
      restoration of the external limiting membrane and persistent irregularity of the
      outer photoreceptor layers. Two individuals with severe vision loss acutely had
      some improvement of Snellen acuity at a 1-year follow-up. CONCLUSION: Handheld
      lasers can produce permanent retinal damage with visual sequelae if improperly
      used. Spectral domain optical coherence tomography demonstrates chronic
      disruption, primarily in the retinal pigment epithelium/photoreceptor region.

PMID- 25380070
TI  - Increases in serum CYFRA21-1 concentration during successful treatment with
      crizotinib.
AB  - BACKGROUND: Increases in tumor marker concentrations usually suggest disease
      progression. CASE REPORT: We here describe on 3 patients with non-small cell lung
      cancer whose serum concentrations of CYFRA21-1 increased in spite of successful
      treatment with crizotinib. Discontinuation of crizotinib resulted in a rapid
      decrease in serum CYFRA21-1 concentrations in all cases. In 1 patient with
      progressive disease, in spite of increasing the dose of crizotinib, CYFRA21-1
      concentrations decreased. CONCLUSIONS: Crizotinib can induce increases in CYFRA21
      1 concentration without disease progression. Pulmonologists and oncologists
      should be aware of this novel phenomenon, and focus on interpretation of CYFRA21
      1 concentrations in monitoring tumor response to crizotinib treatment.

PMID- 25380071
TI  - Novel hold-release functionality in a P300 brain-computer interface.
AB  - Assistive technology control interface theory describes interface activation and
      interface deactivation as distinct properties of any control interface.
      Separating control of activation and deactivation allows precise timing of the
      duration of the activation. Objective. We propose a novel P300 brain-computer
      interface (BCI) functionality with separate control of the initial activation and
      the deactivation (hold-release) of a selection. Approach. Using two different
      layouts and off-line analysis, we tested the accuracy with which subjects could
      (1) hold their selection and (2) quickly change between selections. Main results.
      Mean accuracy across all subjects for the hold-release algorithm was 85% with one
      hold-release classification and 100% with two hold-release classifications. Using
      a layout designed to lower perceptual errors, accuracy increased to a mean of 90%
      and the time subjects could hold a selection was 40% longer than with the
      standard layout. Hold-release functionality provides improved response time (6-16
      times faster) over the initial P300 BCI selection by allowing the BCI to make
      hold-release decisions from very few flashes instead of after multiple sequences
      of flashes. Significance. For the BCI user, hold-release functionality allows for
      faster, more continuous control with a P300 BCI, creating new options for BCI
      applications. 

PMID- 25380073
TI  - Considerations for safe EMS transport of patients infected with Ebola virus.
AB  - The Nebraska Biocontainment Unit through the Nebraska Medical Center in Omaha,
      Nebraska, recently received patients with confirmed Ebola virus from West Africa.
      The Nebraska Biocontainment Unit and Omaha Fire Department's emergency medical
      services (EMS) coordinated patient transportation from airport to the high-level
      isolation unit. Transportation of these highly infectious patients capitalized on
      over 8 years of meticulous planning and rigorous infection control training to
      ensure the safety of transport personnel as well as the community during
      transport. Although these transports occurred with advanced notice and after
      confirmed Ebola virus disease (EVD) diagnosis, approaches and key lessons
      acquired through this effort will advance the ability of any EMS provider to
      safely transport a confirmed or suspected patient with EVD. Three critical areas
      have been identified from our experience: ambulance preparation, appropriate
      selection and use of personal protective equipment, and environmental
      decontamination. 

PMID- 25380076
TI  - Closing the genotype-phenotype gap: emerging technologies for evolutionary
      genetics in ecological model vertebrate systems.
AB  - The analysis of genetic and epigenetic mechanisms of the genotype-phenotypic
      connection has, so far, only been possible in a handful of genetic model systems.
      Recent technological advances, including next-generation sequencing methods such
      as RNA-seq, ChIP-seq and RAD-seq, and genome-editing approaches including CRISPR
      Cas, now permit to address these fundamental questions of biology also in
      organisms that have been studied in their natural habitats. We provide an
      overview of the benefits and drawbacks of these novel techniques and experimental
      approaches that can now be applied to ecological and evolutionary vertebrate
      models such as sticklebacks and cichlid fish. We can anticipate that these new
      methods will increase the understanding of the genetic and epigenetic factors
      influencing adaptations and phenotypic variation in ecological settings. These
      new arrows in the methodological quiver of ecologist will drastically increase
      the understanding of the genetic basis of adaptive traits - leading to a further
      closing of the genotype-phenotype gap. 

PMID- 25380075
TI  - Infantile hepatitis B in immunized children: risk for fulminant hepatitis and
      long-term outcomes.
AB  - BACKGROUND: Infantile hepatitis B after neonatal immunoprophylaxis is a rare yet
      distinct disease. This study aimed to analyze the long-term outcomes and risk
      factors in immunized infants with hepatitis B. METHODS: The clinical parameters
      and outcomes of 41 infants born after universal immunization, and admitted for
      HBV-positive hepatitis were studied. All patients were followed for at least 6
      months (median  = 4.4 years, range 0.6-18.1 years). Patient survival, changes of
      HBsAg and HBeAg status, and complications were analyzed. RESULTS: Among the 41
      cases (32 males, 9 females), 21 presented with fulminant hepatitis (FH), and 20
      with non-fulminant hepatitis (NFH). Ninety-five percent (36/38) of the mothers
      were positive for hepatitis B surface antigen (HBsAg). Multivariate analyses
      revealed younger age of onset (age <7 months) and negative maternal hepatitis B e
      antigen (HBeAg) were associated with FH (p = 0.03 and p = 0.01, respectively). An
      infantile fulminant hepatitis B risk score using maternal/infant HBeAg positivity
      and onset age was proposed. Among the FH cases, the rate of mortality, HBsAg
      clearance, and chronic HBV infection were 47.6%, 38.1%, and 14.3%, respectively.
      Among the NFH cases, 35% developed chronic infection. Of the 9 chronically
      infected children received long-term follow-up, 8 had HBeAg seroconversion before
      4 years of age. One case of FH developed hepatocellular carcinoma 14 years later.
      CONCLUSIONS: Maternal HBsAg + /HBeAg- and early onset age were risk factors for
      FH in immunized infants. A significant portion of patients with FH or NFH evolve
      to chronic HBV infection, with HBeAg seroconversion in young childhood. Close
      surveillance for hepatocellular carcinoma is warranted in patients surviving
      infantile hepatitis B.

PMID- 25380074
TI  - Three-dimensional computer model of the right atrium including the sinoatrial and
      atrioventricular nodes predicts classical nodal behaviours.
AB  - The aim of the study was to develop a three-dimensional (3D) anatomically
      detailed model of the rabbit right atrium containing the sinoatrial and
      atrioventricular nodes to study the electrophysiology of the nodes. A model was
      generated based on 3D images of a rabbit heart (atria and part of ventricles),
      obtained using high-resolution magnetic resonance imaging. Segmentation was
      carried out semi-manually. A 3D right atrium array model (~3.16 million
      elements), including eighteen objects, was constructed. For description of
      cellular electrophysiology, the Rogers-modified FitzHugh-Nagumo model was further
      modified to allow control of the major characteristics of the action potential
      with relatively low computational resource requirements. Model parameters were
      chosen to simulate the action potentials in the sinoatrial node, atrial muscle,
      inferior nodal extension and penetrating bundle. The block zone was simulated as
      passive tissue. The sinoatrial node, crista terminalis, main branch and roof
      bundle were considered as anisotropic. We have simulated normal and abnormal
      electrophysiology of the two nodes. In accordance with experimental findings: (i)
      during sinus rhythm, conduction occurs down the interatrial septum and into the
      atrioventricular node via the fast pathway (conduction down the crista terminalis
      and into the atrioventricular node via the slow pathway is slower); (ii) during
      atrial fibrillation, the sinoatrial node is protected from overdrive by its long
      refractory period; and (iii) during atrial fibrillation, the atrioventricular
      node reduces the frequency of action potentials reaching the ventricles. The
      model is able to simulate ventricular echo beats. In summary, a 3D anatomical
      model of the right atrium containing the cardiac conduction system is able to
      simulate a wide range of classical nodal behaviours. 

PMID- 25380077
TI  - Shared care or nurse consultations as an alternative to rheumatologist follow-up
      for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA:
      cost-effectiveness based on a 2-year randomized trial.
AB  - OBJECTIVES: To compare the cost-effectiveness of three types of follow-up for
      outpatients with stable low-activity rheumatoid arthritis (RA). METHOD: In total,
      287 patients were randomized to either planned rheumatologist consultations,
      shared care without planned consultations, or planned nurse consultations.
      Effectiveness measures included disease activity (Disease Activity Score based on
      28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health
      Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ
      5D). Cost measures included activities in outpatient clinics and general
      practice, prescription and non-prescription medicine, dietary supplements, other
      health-care resources, and complementary and alternative care. Measures of
      effectiveness and costs were collected by self-reported questionnaires at
      inclusion and after 12 and 24 months. Incremental cost-effectiveness rates
      (ICERs) were estimated in comparison with rheumatologist consultations. RESULTS:
      Changes in disease activity, functional status, and health-related quality of
      life were not statistically significantly different for the three groups,
      although the mean scores were better for the shared care and nurse care groups
      compared with the rheumatologist group. Shared care and nurse care were non
      significantly less costly than rheumatologist care. As both shared care and nurse
      care were associated with slightly better EQ-5D improvements and lower costs,
      they dominated rheumatologist care. At EUR 10,000 per quality-adjusted life year
      (QALY) threshold, shared care and nurse care were cost-effective with more than
      90% probability. Nurse care was cost-effective in comparison with shared care
      with 75% probability. CONCLUSIONS: Shared care and nurse care seem to cost less
      but provide broadly similar health outcomes compared with rheumatologist
      outpatient care. However, it is still uncertain whether nurse care and shared
      care are cost-effective in comparison with rheumatologist outpatient care.

PMID- 25380078
TI  - Schottky contact on ultra-thin silicon nanomembranes under light illumination.
AB  - By repeating oxidation and subsequent wet chemical etching, we produced ultra
      thin silicon nanomembranes down to 10 nm based on silicon-on-insulator structures
      in a controllable way. The electrical property of such silicon nanomembranes is
      highly influenced by their contacts with metal electrodes, in which Schottky
      barriers (SBs) can be tuned by light illumination due to the surface doping.
      Thermionic emission theory of carriers is applied to estimate the SB at the
      interface between metal electrodes and Si nanomembranes. Our work reveals that
      the Schottky contacts with Si nanomembranes can be influenced by external stimuli
      (like light luminescence or surface state) more heavily compared to those in the
      thicker ones, which implies that such ultra-thin-film devices could be of
      potential use in optical detectors. 

PMID- 25380079
TI  - Deep transverse friction massage for treating lateral elbow or lateral knee
      tendinitis.
AB  - Background Deep transverse friction massage, one of several physical therapy
      interventions suggested for the management of tendinitis pain, was first
      demonstrated in the 1930s by Dr James Cyriax, a renowned orthopedic surgeon in
      England. Its goal is to prevent abnormal fibrous adhesions and abnormal scarring.
      This is an update of a Cochrane review first published in 2001.Objectives To
      assess the benefits and harms of deep transverse friction massage for treating
      lateral elbow or lateral knee tendinitis.Search methods We searched the following
      electronic databases: the specialized central registry of the Cochrane Field of
      Physical and Related Therapies,the Cochrane Central Register of Controlled Trials
      (CENTRAL),MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), Clinicaltrials.gov, and the Physiotherapy Evidence Database
      (PEDro), up until July 2014. The reference lists of these trials were consulted
      for additional studies.Selection criteria All randomized controlled trials (RCTs)
      and controlled clinical trials (CCTs) comparing deep transverse friction massage
      with control or other active interventions for study participants with two
      eligible types of tendinitis (ie, extensor carpi radialis tendinitis (lateral
      elbow tendinitis, tennis elbow or lateral epicondylitis or lateralis
      epicondylitis humeri) and iliotibial band friction syndrome (lateral knee
      tendinitis)) were selected. Only studies published in English and French
      languages were included.Data collection and analysis Two review authors
      independently assessed the studies on the basis of inclusion and exclusion
      criteria. Results of individual trials were extracted from the included study
      using extraction forms prepared by two independent review authors before the
      review was begun.Data were cross-checked by a third review author. Risk of bias
      of the included studies was assessed using the "Risk of bias"tool of The Cochrane
      Collaboration. A pooled analysis was performed using mean difference (MD) for
      continuous outcomes and risk ratio (RR)for dichotomous outcomes with 95%
      confidence intervals (CIs).Main results Two RCTs (no new additional studies in
      this update) with 57 participants met the inclusion criteria. These studies
      demonstrated high risk of performance and detection bias, and the risk of
      selection, attrition, and reporting bias was unclear.The first study included 40
      participants with lateral elbow tendinitis and compared (1) deep transverse
      friction massage combined with therapeutic ultrasound and placebo ointment (n =
      11) versus therapeutic ultrasound and placebo ointment only (n = 9) and (2)deep
      transverse friction massage combined with phonophoresis (n = 10) versus
      phonophoresis only (n = 10). No statistically significant differences were
      reported within five weeks for mean change in pain on a 0 to 100 visual analog
      scale (VAS) (MD -6.60, 95%CI -28.60 to 15.40; 7% absolute improvement), grip
      strength measured in kilograms of force (MD 0.10, 95% CI -0.16 to 0.36) and
      function ona 0 to 100 VAS (MD -1.80, 95% CI -0.18.64 to 15.04; 2% improvement),
      pain-free function index measured as the number of painfree items (MD 1.10, 95%
      CI -1.00 to 3.20) and functional status (RR 3.3, 95% CI 0.4 to 24.3) for deep
      transverse friction massage,and therapeutic ultrasound and placebo ointment
      compared with therapeutic ultrasound and placebo ointment only. Likewise for deep
      transverse friction massage and phonophoresis compared with phonophoresis alone,
      no statistically significant differences were found for pain (MD -1.2, 95% CI 
      20.24 to 17.84; 1% improvement), grip strength (MD -0.20, 95% CI -0.46 to 0.06)
      and function (MD3.70, 95% CI -14.13 to 21.53; 4% improvement). In addition, the
      GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach
      was used to evaluate the quality of evidence for the pain outcome, which received
      a score of "very low".Pain relief of 30% or greater, quality of life, patient
      global assessment, adverse events, and withdrawals due to adverse events were not
      assessed or reported.The second study included 17 participants with iliotibial
      band friction syndrome (knee tendinitis) and compared deep transverse friction
      massage with physical therapy intervention versus physical therapy intervention
      alone, at two weeks. Deep transverse friction massage with physical therapy
      intervention showed no statistically significant differences in the three
      measures of pain relief on a 0 to 10 VAS when compared with physical therapy
      alone: daily pain (MD -0.40, 95% CI -0.80 to -0.00; absolute improvement 4%),
      pain while running (scale from 0 to 150) (MD -3.00, 95% CI -11.08 to 5.08), and
      percentage of maximum pain while running (MD -0.10, 95% CI -3.97 to 3.77). For
      the pain outcome, absolute improvement showed a 4% reduction in pain. However,
      the quality of the body of evidence received a grade of "very low."Pain relief of
      30% or greater, function, quality of life, patient global assessment of success,
      adverse events, and withdrawals due to adverse events were not assessed or
      reported.Authors' conclusions We do not have sufficient evidence to determine the
      effects of deep transverse friction on pain, improvement in grip strength, and
      functional status for patients with lateral elbow tendinitis or knee tendinitis,
      as no evidence of clinically important benefits was found.The confidence
      intervals of the estimate of effects overlapped the null value for deep
      transverse friction massage in combination with physical therapy compared with
      physical therapy alone in the treatment of lateral elbow tendinitis and knee
      tendinitis. These conclusions are limited by the small sample size of the
      included randomized controlled trials. Future trials, utilizing specific methods
      and adequate sample sizes, are needed before conclusions can be drawn regarding
      the specific effects of deep transverse friction massage on lateral elbow
      tendinitis.

PMID- 25380080
TI  - Controlled mechnical modification of manganite surface with nanoscale resolution.
AB  - We investigated the surfaces of magnetoresistive manganites, La(1-x)Ca(x)MnO3 and
      La(2-2x)Sr(1+2x)Mn2O7, using a combination of ultrahigh vacuum conductive,
      electrostatic and magnetic force microscopy methods. Scanning as-grown film with
      a metal tip, even with zero applied bias, was found to modify the surface
      electronic properties such that in subsequent scans, the conductivity is reduced
      below the noise level of conductive probe microscopy. Scanned areas also reveal a
      reduced contact potential difference relative to the pristine surface by ~0.3 eV.
      We propose that contact-pressure of the tip modifies the electrochemical
      potential of oxygen vacancies via the Vegard effect, causing vacancy motion and
      concomitant changes of the electronic properties.

PMID- 25380081
TI  - Prevalence and risk factors of hypertension in myanmar: a systematic review and
      meta-analysis.
AB  - Hypertension (HPT) is the most common condition seen in primary care that can
      lead to health consequences and death if not detected early and treated
      appropriately.This study aimed to synthesize the prevalence, awareness, and
      control of HPT, and investigate the risk factors for HPT in Myanmar.We performed
      a meta-analysis of observational studies. Relevant studies were searched in
      electronic databases. The methodological quality of the included studies was
      assessed in 3 domains: selection bias, measurement bias, and bias related to data
      analysis. The overall prevalence and proportions was calculated using random
      effect model of DerSimonian-Laird method. To identify the risk factors for HPT in
      Myanmar, we entered the ratio measures of the (adjusted) effect as a log odds
      ratio (OR) and the standard error of the log OR using generic inverse-variance
      weighting method. For stability of results, we performed leave-one-study-out
      sensitivity analysis by omitting individual studies one at a time from the meta
      analysis.Seven studies (n = 20,901) were included in this analysis. Overall
      prevalence of HPT in Myanmar was 22% (95% confidence interval (CI): 14%-31.7%, I:
      99.6%), stratified as 21.5% (95% CI: 14.1%-29.9%, I: 98.7%) in men and 22.7% (95%
      CI: 10.8%-34.6%, I: 99.5%) in women. Overall, prevalence of HPT increased with an
      advancing age of the participants. The proportions of awareness and controlled
      HPT were 55% (95% CI: 43%-67%, I: 97.7%) and 11% (95% CI: 6%-15%, I: 93.8%),
      respectively. A weak but significant association was observed between HPT and
      alcohol drinking (summary OR: 1.38, 95% CI: 1.14%-1.65, I: 0%) and smoking
      (summary OR: 1.32, 95% CI: 1.0%-1.74, I: 50%). In sensitivity analysis, when a
      study that made confirmation of HPT by the former World Health Organization
      criteria was dropped, the prevalence increased to 26% (95% CI: 20.8%-32.1%, I:
      98.1%).HPT was considerably prevalent in Myanmar, while the levels of awareness
      and controlled HPT were low. Health promotion strategy tailored to the education
      on modifiable risk factors and establishment of blood pressure screening in
      primary health care context would be of immense value. Upcoming well-powered
      studies, using the standardized research design and covering more regions of the
      country are recommended. 

PMID- 25380082
TI  - Predictors of critical acute pancreatitis: a prospective cohort study.
AB  - Critical acute pancreatitis (CAP) has recently emerged as the most ominous
      severity category of acute pancreatitis (AP). As such there have been no studies
      specifically designed to evaluate predictors of CAP. In this study, we aimed to
      evaluate the accuracy of 4 parameters (Acute Physiology and Chronic Health
      Evaluation [APACHE] II score, C-reactive protein [CRP], D-dimer, and intra
      abdominal pressure [IAP]) for predicting CAP early after hospital admission.
      During the study period, data on patients with AP were prospectively collected
      and D-dimer, CRP, and IAP levels were measured using standard methods at
      admission whereas the APACHE II score was calculated within 24 hours of hospital
      admission. The receiver-operating characteristic (ROC) curve analysis was applied
      and the likelihood ratios were calculated to evaluate the predictive accuracy. A
      total of 173 consecutive patients were included in the analysis and 47 (27%) of
      them developed CAP. The overall hospital mortality was 11% (19 of 173). APACHE II
      score >=11 and IAP >=13 mm Hg showed significantly better overall predictive
      accuracy than D-dimer and CRP (area under the ROC curve-0.94 and 0.92 vs. 0.815
      and 0.667, correspondingly). The positive likelihood ratio of APACHE II score is
      excellent (9.9) but of IAP is moderate (4.2). The latter can be improved by
      adding CRP (5.8). In conclusion, of the parameters studied, APACHE II score and
      IAP are the best available predictors of CAP within 24 hours of hospital
      admission. Given that APACHE II score is rather cumbersome, the combination of
      IAP and CRP appears to be the most practical way to predict critical course of AP
      early after hospital admission.

PMID- 25380083
TI  - Positron emission tomography combined with computed tomography as a screening
      tool for occult malignancy in patients with unprovoked venous thromboembolism: an
      observational study.
AB  - Venous thromboembolism (VTE) can be the first clinical manifestation of an occult
      malignancy. We aimed to assess the value, in daily practice, of positron emission
      tomography combined with computed tomography (PET-CT) for occult malignancy
      diagnosis in patients with unprovoked VTE.All PET-CTs performed over 5-years
      period (from January 2009 to October 2013) in adult patients followed in the
      Department of Internal Medicine (Bichat Hospital, Paris, France) were
      retrospectively reviewed. Clinical history, imaging findings, and additional
      diagnostic tests performed because of PET-CT findings were analyzed.From January
      2009 to October 2013, PET-CT was performed for malignancy diagnosis in 67
      consecutive patients with unprovoked VTE. Seventeen patients were excluded
      because of congenital or acquired thrombophilia, known cancer, estrogen use,
      inability to confirm VTE diagnosis, or missing data. Fifty patients (25 women;
      mean age, 65.2 +/- 15.9 years) were included. VTE was a first episode in 84% of
      cases. In 22 (44%) patients, PET-CT showed increased uptake suspicious for
      malignancy. After additional procedures, malignancy was confirmed in 12/22
      patients. In all cases of confirmed malignancies, conventional computed
      tomography scan (CT-scan) had similar diagnosis yield, as compared with PET-CT.
      In 10/22 cases, the suspected diagnosis of malignancy could not be confirmed
      despite extensive workup including specialist visits (n = 5), magnetic resonance
      imaging (n = 4), gastrointestinal tract endoscopy (n = 3), endometrial biopsies
      (n = 2), and hysterectomy (n = 1). The cost of additional diagnosis procedures
      performed because of false positive PET-CT amounted to e1956/patient.
      Interestingly, considering CT-scan findings only, no further investigation would
      have been scheduled. No patient with negative or false positive PET-CT was
      diagnosed with cancer during a mean follow-up of 22 +/- 13.6 months.A diagnosis
      strategy based on PET-CT screening for malignancy in patients with unprovoked VTE
      had limited diagnosis value and may lead to unnecessary alarming and money- and
      time-consuming investigations. 

PMID- 25380084
TI  - Sarcoidosis occurring after lymphoma: report of 14 patients and review of the
      literature.
AB  - Sarcoidosis is a granulomatous disease that most frequently affects the lungs
      with pulmonary infiltrates and/or bilateral hilar and mediastinal
      lymphadenopathy. An association of sarcoidosis and lymphoproliferative disease
      has previously been reported as the sarcoidosis-lymphoma syndrome. Although this
      syndrome is characterized by sarcoidosis preceding lymphoma, very few cases of
      sarcoidosis following lymphoma have been reported. We describe the clinical,
      biological, and radiological characteristics and outcome of 39 patients
      presenting with sarcoidosis following lymphoproliferative disease, including 14
      previously unreported cases and 25 additional patients, after performing a
      literature review. Hodgkin lymphoma and non-Hodgkin lymphoma were equally
      represented. The median delay between lymphoma and sarcoidosis was 18 months.
      Only 16 patients (41%) required treatment. Sarcoidosis was of mild intensity or
      self-healing in most cases, and overall clinical response to sarcoidosis was
      excellent with complete clinical response in 91% of patients. Sarcoidosis was
      identified after a follow-up computerized tomography scan (CT-scan) or
      fluorodeoxyglucose-positron emission tomography/computerized tomography (FDG
      PET/CT) evaluation in 18/34 patients (53%). Sarcoidosis is therefore a
      differential diagnosis to consider when lymphoma relapse is suspected on a CT
      scan or FDG-PET/CT, emphasizing the necessity to rely on histological
      confirmation of lymphoma relapse. 

PMID- 25380085
TI  - The relationship between elemental carbon and diesel particulate matter in
      underground metal/nonmetal mines in the United States and coal mines in
      Australia.
AB  - In the United States, total carbon (TC) is used as a surrogate for determining
      diesel particulate matter (DPM) compliance exposures in underground
      metal/nonmetal mines. Since TC can be affected by interferences and elemental
      carbon (EC) is not, one method used to estimate the TC concentration is to
      multiply the EC concentration from the personal sample by a conversion factor to
      avoid the influence of potential interferences. Since there is no accepted single
      conversion factor for all metal/nonmetal mines, one is determined every time an
      exposure sample is taken by collecting an area sample that represents the TC/EC
      ratio in the miner's breathing zone and is away from potential interferences. As
      an alternative to this procedure, this article investigates the relationship
      between TC and EC from DPM samples to determine if a single conversion factor can
      be used for all metal/nonmetal mines. In addition, this article also investigates
      how well EC represents DPM concentrations in Australian coal mines since the
      recommended exposure limit for DPM in Australia is an EC value. When TC was
      predicted from EC values using a single conversion factor of 1.27 in 14 US
      metal/nonmetal mines, 95% of the predicted values were within 18% of the measured
      value, even at the permissible exposure limit (PEL) concentration of 160 MUg/m(3)
      TC. A strong correlation between TC and EC was also found in nine underground
      coal mines in Australia. 

PMID- 25380087
TI  - The origin of the antiferromagnetic behaviour of the charge-transfer compound
      (HMTTF)[Ni(mnt)2].
AB  - The charge-transfer (HMTTF)[Ni(mnt)2] material (1) was the first mixed-stack
      compound reported to present ferromagnetic (FM) interactions between the donor
      (D) and acceptor (A) units within each mixed-stack. Despite the presence of a
      dominant FM interaction, its magnetic susceptibility curve, chi(T), corresponded
      to that of an antiferromagnetic (AFM) compound at low temperatures, a fact that
      was tentatively explained in terms of a FM-to-AFM magnetic transition. In this
      work, the First-Principles Bottom-Up procedure has been applied to rationalize
      the magnetic properties of 1. The results presented herein indicate the presence
      of up to five sizeable JAB magnetic exchange interactions (26.0, -1.7, 1.9, 0.1,
      and -99.3 cm(-1)) that create a complex 2D magnetic network. This magnetic
      topology not only produces a calculated chi(T) curve that is in excellent
      agreement with the experimental measurements, but also allows us to understand
      the magnetic behaviour of 1, in the full range of temperatures, solely in terms
      of the different Boltzmann population of diamagnetic and paramagnetic spin states
      as the temperature changes. Our data thus provide a plausible explanation for the
      AFM behaviour of 1 at low temperatures that does not involve a phase transition. 

PMID- 25380088
TI  - Recent cancer survival in Germany: an analysis of common and less common cancers.
AB  - The monitoring of cancer survival by population-based cancer registries is a
      prerequisite to evaluate the current quality of cancer care. Our study provides 1
      , 5- and 10-year relative survival as well as 5-year relative survival
      conditional on 1-year survival estimates and recent survival trends for Germany
      using data from 11 population-based cancer registries, covering around one-third
      of the German population. Period analysis was used to estimate relative survival
      for 24 common and 11 less common cancer sites for the period 2007-2010. The
      German and the United States survival estimates were compared using the
      Surveillance, Epidemiology and End Results 13 database. Trends in cancer survival
      in Germany between 2002-2004 and 2008-2010 were described. Five-year relative
      survival increased in Germany from 2002-2004 to 2008-2010 for most cancer sites.
      Among the 24 most common cancers, largest improvements were seen for multiple
      myeloma (8.0% units), non-Hodgkin lymphoma (6.2% units), prostate cancer (5.2%
      units) and colorectal cancer (4.6% units). In 2007-2010, the survival
      disadvantage in Germany compared to the United States was largest for cancers of
      the mouth/pharynx (-11.0% units), thyroid (-6.8% units) and prostate (-7.5%
      units). Although survival estimates were much lower for elderly patients in both
      countries, differences in age patterns were observed for some cancer sites. The
      reported improvements in cancer survival might reflect advances in the quality of
      cancer care on the population level as well as increased use of screening in
      Germany. The survival differences across countries and the survival disadvantage
      in the elderly require further investigation. 

PMID- 25380086
TI  - Arctigenin in combination with quercetin synergistically enhances the
      antiproliferative effect in prostate cancer cells.
AB  - SCOPE: We investigated whether a combination of two promising chemopreventive
      agents arctigenin (Arc) and quercetin (Q) increases the anticarcinogenic potency
      at lower concentrations than necessary when used individually in prostate cancer.
      METHODS AND RESULTS: Androgen-dependent LAPC-4 and LNCaP prostate cancer cells
      were treated with low doses of Arc and Q alone or in combination for 48 h. The
      antiproliferative activity of Arc was 10- to 20-fold stronger than Q in both cell
      lines. Their combination synergistically enhanced the antiproliferative effect,
      with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in
      AR mutated LNCaP cells. Arc demonstrated a strong ability to inhibit AR protein
      expression in LAPC-4 cells. The combination treatment significantly inhibited
      both AR and PI3K/Akt pathways compared to control. A protein array analysis
      revealed that the mixture targets multiple pathways particularly in LAPC-4 cells
      including Stat3 pathway. The mixture significantly inhibited the expression of
      several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to
      control. The mixture also enhanced the inhibition of cell migration in both cell
      lines compared to individual compounds tested. CONCLUSION: The combination of Arc
      and Q that target similar pathways, at low physiological doses, provides a novel
      regimen with enhanced chemoprevention in prostate cancer.

PMID- 25380089
TI  - British Fertility Society Policy and Practice Committee: prevention of ovarian
      hyperstimulation syndrome.

PMID- 25380090
TI  - Discussion on The risorius muscle: anatomic considerations with reference to
      botulinum neurotoxin injection for masseteric hypertrophy.

PMID- 25380091
TI  - Lidocaine contact allergy is becoming more prevalent.
AB  - BACKGROUND: Allergic contact dermatitis (ACD) to lidocaine is rising in
      prevalence. This is due to a growing number of over-the-counter (OTC) products
      containing topical amide and ester anesthetics. The phenomenon poses a real
      threat to the authors' surgical anesthetic options. OBJECTIVE: To investigate the
      epidemiology of topical anesthetic ACD in British Columbia, Canada and provide an
      approach for clinicians to deal with this problem. MATERIALS AND METHODS: A
      retrospective chart review of 1,819 patients who underwent patch testing at the
      University of British Columbia Contact Dermatitis Clinic between January 2009 and
      June 2013 was completed. The authors also performed a detailed review of Canadian
      OTC preparations containing lidocaine in 2013. RESULTS: The prevalence of ACD to
      local anesthetics is significant at 2.4%. The most common allergen is benzocaine
      (45%) followed by lidocaine (32%) and dibucaine (23%). CONCLUSION: The proportion
      of ACD caused by lidocaine is higher than expected. This is likely secondary to
      an increase in OTC medicaments containing lidocaine. Patients who are patch test
      positive to a local anesthetic should be challenged intradermally to confirm
      clinical relevance. Because ACD is a delayed Type IV hypersensitivity reaction
      (localized dermatitis), the risk of anaphylaxis is not a concern.

PMID- 25380092
TI  - Fractional CO2 laser is an effective therapeutic modality for xanthelasma
      palpebrarum: a randomized clinical trial.
AB  - BACKGROUND: Xanthelasma palpebrarum (XP) is a common cosmetic concern. Although
      there is a wide range of therapeutic modalities for XP, there is no general
      consensus on the optimal treatment for such condition. OBJECTIVE: Compare the
      efficacy and safety of super pulsed (SP) and fractional CO2 lasers in the
      treatment of XP. PATIENTS AND METHODS: This prospective randomized comparative
      clinical study included 20 adult patients with bilateral and symmetrical XP
      lesions. Xanthelasma palpebrarum lesions were randomly assigned to treatment by
      either single session of ablative SP CO2 laser or 3 to 5 sessions of ablative
      fractional CO2 laser with monthly intervals. All patients were assessed using
      digital photography and optical coherence tomography images. RESULTS: Xanthelasma
      palpebrarum lesions on both sides were successfully removed with significant
      improvement in size, color, and thickness. Although lesions treated by SP CO2
      laser showed significantly better improvement regarding color and thickness of
      the lesions, downtime and patient satisfaction were significantly better for
      lesions treated with fractional CO2 laser. Scarring and recurrence were
      significantly higher in lesions treated by SP CO2 laser. CONCLUSION: Ablative
      fractional CO2 laser is an effective and safe therapeutic option for XP with
      significantly shorter downtime and higher patient satisfaction compared with SP
      CO2 laser.

PMID- 25380093
TI  - Repositioning the Cobb human archive: the merger of a skeletal collection and its
      texts.
AB  - The W. Montague Cobb skeletal collection, mainly comprised of African Americans
      living in Washington, DC, before 1969, is an important collection for human
      biological studies of the African Diaspora. This article outlines the process of
      constructing an improved study sample for biocultural analysis by merging
      skeletal remains from the collection with their associated texts. The merging
      allows for the inclusion of individuals from the original series for whom we no
      longer have skeletons. We argue that this step is necessary to construct a data
      set that reflects the demographic breadth (age, ethnicity, social class) of the
      original collection, taking into account a substantial number of skeletons lost
      during storage and disuse. The mechanics of this process were informed by a
      critical and humanistic orientation toward human biological study built upon the
      following premises: (1) scientific investigation is not an objective or passive
      practice, nor must it be; and, (2) relevant, publically accessible human
      biological research requires competence with social justice issues, as well as
      previous and current scholarship focused on addressing those issues. This
      approach to sample construction engages skeletal remains as biological and social
      products, and enhances the social and translational implications of our research
      practices.

PMID- 25380094
TI  - Silicon-substituted xanthene dyes and their applications in bioimaging.
AB  - Fluorescence imaging is one of the most powerful techniques for visualizing
      temporal and spatial changes of biological phenomena in living cells, and many
      fluorescent probes have been developed. In particular, xanthene dyes such as
      fluorescein and rhodamines have favorable characteristics, such as high water
      solubility, high fluorescence quantum yield and high molar extinction
      coefficient, and they have been utilized as fluorescent cores for fluorescent
      probes working in the green to red wavelength region. Recently, silicon
      substituted xanthene dyes such as 2,7-N,N,N',N'-tetramethyl-9-dimethyl-10-hydro-9
      silaanthracene (TMDHS), Si-rhodamines and TokyoMagentas, in which the O atom at
      the 10-position of xanthene is replaced with a Si atom, have been developed as
      novel far-red to near-infrared fluorescent cores that retain the key advantages
      of the parent structures. Fluorescent probes based on them have opened up new
      possibilities for imaging biological processes in living cells. This minireview
      covers recent progress in silicon-substituted xanthene dyes, including
      representative applications for in vivo tumor imaging, triple-color imaging of
      neuronal activity, and super-resolution microscopy. 

PMID- 25380095
TI  - Particle size distribution of halogenated flame retardants and implications for
      atmospheric deposition and transport.
AB  - This study investigates the distribution of polybrominated diphenyl ethers
      (PBDEs), hexabromocyclododecane (HBCD) and a group of novel flame retardants
      (NFRs) on atmospheric aerosols. Two high volume cascade impactors were used to
      collect particulate fractions of ambient air over a one year period at urban and
      rural sites. The majority of FRs were found on the finest aerosols (<0.95 MUm).
      Concentrations of HBCD were higher than those of SigmaPBDEs. Moreover, we noted
      seasonality and spatial differences in particle size distributions, yet a large
      portion of the observed differences were due to differences in particulate matter
      (PM) itself. When normalized by PM, the size distributions of the FRs exhibited
      much greater heterogeneity. Differences existed between the FR distributions by
      molecular weight, with the higher molecular weight FRs (e.g., BDE-209, Dechlorane
      Plus) distributed more uniformly across all particulate size fractions. The
      seasonal, spatial, and compound-specific differences are of crucial importance
      when estimating dry and wet deposition of FRs as smaller aerosols have longer
      atmospheric residence times. Estimated wet and dry deposition of four
      representative FRs (BDE-47, BDE-209, HBCD, and Dechlorane Plus) using size
      segregated aerosol data resulted in lower deposition estimates than when bulk
      aerosol data were used. This has implications for estimates of long-range
      atmospheric transport and atmospheric residence times, as it suggests that
      without size-specific distributions, these parameters could be underestimated for
      FRs. 

PMID- 25380097
TI  - When a diabetic foot ulcer results in amputation: a qualitative study of the
      lived experience of 15 patients.
AB  - Diabetes is a chronic disease that can lead to complications resulting in
      diabetic foot ulcers (DFUs), foot infections, osteomyelitis, and amputations.
      Almost 50,000 amputations performed every year in the United States are due to
      DFUs. A qualitative analysis using Colaizzi's step-by-step approach to
      phenomenology was conducted to describe the experiences of 15 patients with
      diabetes living with a foot amputation. Semi-structured interviews were recorded
      digitally,transcribed, and analyzed. The analysis included reading transcripts
      multiple times, identifying noteworthy verbatim statements, then abstracting key
      words and phrases; similar key words and phrases were grouped into a meaning
      unit. The researchers rereviewed original transcripts, verbatim statements, and
      extracted key words and phrases and devised meaning units to identify main
      themes. Rigor in this study was ensured by developing an audit trail that linked
      the meaning units and themes back to key words and verbatim statements in the
      original transcripts and then allowing the participant to ensure accuracy of
      recounted information. Five major themes emerged from the data regarding patient
      concern about the ability to be productive members of society (i.e.,
      transitioning from having a nonhealing wound to living as a new amputee)-
      financial burden, powerlessness, social support, placing blame, and uncertainty
      in one's continued ability--each having implications for health care providers as
      well as patients. By considering the experience from the patient perspective,
      health care professionals may be better prepared to discuss patient concerns with
      follow-up care and day to-day living, especially in getting help with finances.
      Additional research is needed to uncover models of care that may help these
      patients remain productive members of society and reduce the burden of amputation
      on patient quality of life.

PMID- 25380098
TI  - The Association for the Advancement of Wound Care (AAWC) venous and pressure
      ulcer guidelines.
AB  - Guidelines based on best available evidence to support pressure ulcer (PU) or
      venous ulcer (VU) management decisions can improve outcomes. Historically, such
      guidelines were consensus-based and differed in content and development methods
      used. Since 2002, the Association for the Advancement of Wound Care (AAWC)
      Guideline Task Force has used a systematic approach for developing "guidelines of
      guidelines" that unify and blend recommendations from relevant published
      guidelines while meeting Institute of Medicine and Agency for Healthcare Research
      and Quality standards. In addition to establishing the literature-based strength
      of each recommendation, guideline clinical relevance is examined using standard
      content validation procedures. All final recommendations included are clinically
      relevant and/or supported by the highest level of available evidence, cited with
      every recommendation. In addition, guideline implementation resources are
      provided. The most recent AAWC VU and PU guidelines and ongoing efforts for
      improving their clinical relevance are presented. The guideline development
      process must be transparent and guidelines must be updated regularly to maintain
      their relevance. In addition, end-user results and research studies to examine
      their construct and predictive validity are needed. 

PMID- 25380100
TI  - L-Valine derived chiral N-sulfinamides as effective organocatalysts for the
      asymmetric hydrosilylation of N-alkyl and N-aryl protected ketimines.
AB  - L-Valine derived N-sulfinamides have been developed as efficient enantioselective
      Lewis basic organocatalysts for the asymmetric reduction of N-aryl and N-alkyl
      ketimines with trichlorosilane. Catalyst 3c afforded up to 99% yield and 96% ee
      in the reduction of N-alkyl ketimines and up to 98% yield and 98% ee in the
      reduction of N-aryl ketimines.

PMID- 25380101
TI  - Enhanced catalytic activity toward O2 reduction on Pt-modified La1-xSrxCo1-yFeyO3
      delta cathode: a combination study of first-principles calculation and
      experiment.
AB  - Using the first-principles calculation and the electronic conductivity relaxation
      (ECR) experimental technique, we investigated the adsorption and dissociation
      behaviors of O2 on Pt-modified La0.625Sr0.375Co0.25Fe0.75O3-delta (LSCF) surface.
      Toward the O2 reduction, the calculation results show that the perfect LSCF (100)
      surface is catalytically less active than both the defective (100) surface and
      the perfect (110) surface. O2 molecule can weakly adsorb on the perfect LSCF
      (100) surface with a small adsorption energy of about -0.30 eV, but the
      dissociation energy barrier of the O2 molecule is about 1.33-1.43 eV. Doping of
      Pt cluster on the LSCF (100) surface can remarkably enhance its catalytic
      activity. The adsorption energies of O2 molecules become -1.16 and -1.89 eV for
      the interfacial Feint site and the Ptbri bridge site of Pt4-cluster,
      respectively. Meanwhile, the dissociation energy barriers are reduced to 0.37 and
      0.53 eV, respectively. The migration energy barrier of the dissociated oxygen
      from the interfacial Pt to the LSCF surface is 0.66 eV, and it is 2.58 eV from
      the top site of the Pt cluster to the interfacial Pt site, suggesting that it is
      extremely difficult for oxygen to migrate over the Pt cluster. The Bader charge
      analysis results further indicate that the charges transferring from Pt cluster
      to LSCF surface promote the adsorption and dissociation of O2 molecules.
      Experimentally, a dramatic decrease of the surface oxygen exchange relaxation
      time was observed on Pt-modified LSCF cathode, with a chemical surface exchange
      coefficient increased from 6.05 * 10(-5) cm/s of the bare LSCF cathode to 4.04 *
      10(-4) cm/s of the Pt-modified LSCF cathode, agreeing very well with our
      theoretical predictions.

PMID- 25380102
TI  - Characterization of ion-irradiated poly-L-lactic acid using nano-cutting.
AB  - Effects on the mechanical strength of poly-L-lactic acid (PLLA) upon irradiation
      with 150 keV He(+) ion were studied. Changes in the irradiated surface were
      investigated using a surface texture and contour measuring instrument and an
      atomic force microscope. Observations made with the atomic force microscope
      revealed that the irradiated surface subsided significantly as the fluence
      increased. In order to investigate the dependence on fluence of the depth of the
      Bragg peak for the ion implantation, the cutting strength, Sigma, was analysed
      [F. Saito, I. Nishiyama and T. Hyodo, Mater. Lett., 2012, 66, 144-146]; this
      value is an indicator of the strength of a material against cutting, and is
      obtained from the cutting resistance. The averaged ion projected range increased
      from about 1.1 MUm for a fluence of 1 * 10(15) He(+)/cm(2) to about 4 MUm for a
      fluence of 1 * 10(16) He(+)/cm(2). The density of the region following
      irradiation was estimated using a combination of cutting resistance measurements
      and positron annihilation gamma ray Doppler broadening measurements made with an
      energy-variable positron beam. The density decreased from the value of 1.27 g cm(
      3) to about 0.6 g cm(-3) after irradiation with a fluence of 3 * 10(15)
      He(+)/cm(2). By considering the decrease in the density and the subsidence of the
      surface, it is concluded that only 30% of the original weight remained in the
      irradiated region after exposure to the He(+) ions. Anisotropic change in the
      cutting resistance suggests that mechanical strength in the direction normal to
      the surface increased while that in the lateral direction decreased.

PMID- 25380103
TI  - International rotations and resident education.

PMID- 25380104
TI  - Outcome methods used in clinical studies of Chiari malformation Type I: a
      systematic review.
AB  - OBJECT: Chiari malformation Type I (CM-I) is a common and often debilitating
      neurological disease. Efforts to improve treatment of CM-I are impeded by
      inconsistent and limited methods of evaluating clinical outcomes. To understand
      current approaches and lay a foundation for future research, the authors
      conducted a systematic review of the methods used in original published research
      articles to evaluate clinical outcomes in patients treated for CM-I. METHODS: The
      authors searched PubMed, Embase, the Cumulative Index to Nursing and Allied
      Health Literature, ClinicalTrials.gov , and Cochrane databases to identify
      publications between January 2003 and August 2013 that met the following
      criteria: 1) reported clinical outcomes in patients treated for CM-I; 2) were
      original research articles; 3) included at least 10 patients or, if a comparative
      study, at least 5 patients per group; and 4) were restricted to patients with CM
      I. RESULTS: Among the 74 papers meeting inclusion criteria, there was wide
      variation in the outcome methods used. However, all approaches were broadly
      grouped into 3 categories: 1) "gestalt" impression of overall symptomatic
      improvement (n=45 papers); 2) postoperative change in specific signs or symptoms
      (n=20); or 3) results of various standardized assessment scales (n=22). Among
      standardized scales, 11 general function measures were used, compared with 6
      disease-specific tools. Only 3 papers used scales validated in patients with CM
      I. To facilitate a uniform comparison of these heterogeneous approaches, the
      authors appraised articles in multiple domains defined a priori as integral to
      reporting clinical outcomes in CM-I. Notably, only 7 articles incorporated
      patient-response instruments when reporting outcome, and only 22 articles
      explicitly assessed quality of life. CONCLUSIONS: The methods used to evaluate
      clinical outcomes in CM-I are inconsistent and frequently not comparable,
      complicating efforts to analyze results across studies. Development, validation,
      and incorporation of a small number of disease-specific patient-based instruments
      will improve the quality of research and care of CM-I patients.

PMID- 25380105
TI  - Cost-consequence analysis of antibiotic-impregnated shunts and external
      ventricular drains in hydrocephalus.
AB  - OBJECT: Despite multiple preventive strategies for reducing infection, up to 15%
      of patients with shunt catheters and 27% of patients with external ventricular
      drains (EVDs) may develop an infection. There are few data on the cost
      effectiveness of measures to prevent hydrocephalus catheter infection from the
      hospital perspective. The objective of this study was to perform a cost
      consequence analysis to assess the potential clinical and economic value of
      antibiotic-impregnated catheter (AIC) shunts and EVDs compared with non-AIC
      shunts and EVDs in the treatment of hydrocephalus from a hospital perspective.
      METHODS: The authors used decision analytical techniques to assess the clinical
      and economic consequences of using antibiotic-impregnated shunts and EVDs from a
      hospital perspective. Model inputs were derived from the published, peer-reviewed
      literature. Clinical studies comparing infection rates and the clinical and
      economic impact of infections associated with the use of AICs and standard
      catheters (non-AICs) were evaluated. Outcomes assessed included infections,
      deaths due to infection, surgeries due to infection, and cost associated with
      shunt- and EVD-related infection. A subanalysis using only AIC shunt and EVD
      Level I evidence (randomized controlled trial results) was conducted as an
      alternate to the cumulative analysis of all of the AIC versus non-AIC studies (13
      of the 14 shunt studies and 4 of the 6 EVD studies identified were
      observational). Sensitivity analyses were conducted to determine how changes in
      the values of uncertain parameters affected the results of the model. RESULTS: In
      100 patients requiring shunts, AICs may be associated with 0.5 fewer deaths, 71
      fewer hospital days, 11 fewer surgeries, and $128,228 of net savings in hospital
      costs due to decreased infection. Results of the subanalysis showed that AICs may
      be associated with 1.9 fewer deaths, 1611 fewer hospital days, 25 fewer
      surgeries, and $346,616 of net savings in hospital costs due to decreased
      infection. The rate of decrease in infection with AIC shunts was shown to have
      the greatest impact on the cost savings realized with use of AIC shunts. In 100
      patients requiring EVDs, AICs may be associated with 2.7 fewer deaths and 82
      fewer hospital days due to infection. The relative risk of more severe
      neurological impairment was estimated to be 5.33 times greater with EVD
      infection. Decreases in infection with AIC EVDs resulted in an estimated $264,069
      of net savings per 100 patients treated with AICs. Results of the subanalysis
      showed that AIC EVDs may be associated with 1.0 fewer deaths, 31 infection
      related hospital days averted, and $74,631 saved per 100 patients treated with
      AIC EVDs. As was seen with AIC shunts, the rate of decrease in infection with AIC
      EVDs was shown to have the greatest impact on the cost savings realized with use
      of AIC EVDs. CONCLUSIONS: The current value analysis demonstrates that evidence
      supports the use of AICs as effective and potentially cost-saving treatment.

PMID- 25380106
TI  - Intracranial inertial cavitation threshold and thermal ablation lesion creation
      using MRI-guided 220-kHz focused ultrasound surgery: preclinical investigation.
AB  - OBJECT: In biological tissues, it is known that the creation of gas bubbles
      (cavitation) during ultrasound exposure is more likely to occur at lower rather
      than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage.
      Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused
      ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are
      mandatory for laying the groundwork for the use of low-frequency systems in
      future clinical trials. The authors investigate here the in vivo potential
      thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal
      coagulation using MRI, acoustic spectroscopy, and histology. METHODS: Ten female
      piglets that had undergone a craniectomy were sonicated using a 220-kHz
      transcranial MRgFUS system over an acoustic energy range of 5600-14,000 J. For
      each piglet, a long-duration sonication (40-second duration) was performed on the
      right thalamus, and a short sonication (20-second duration) was performed on the
      left thalamus. An acoustic power range of 140-300 W was used for long-duration
      sonications and 300-700 W for short-duration sonications. Signals collected by 2
      passive cavitation detectors were stored in memory during each sonication, and
      any subsequent cavitation activity was integrated within the bandwidth of the
      detectors. Real-time 2D MR thermometry was performed during the sonications. T1
      weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI
      was performed after treatment to assess the lesions. The piglets were killed
      immediately after the last series of posttreatment MR images were obtained. Their
      brains were harvested, and histological examinations were then performed to
      further evaluate the lesions. RESULTS: Two types of lesions were induced: thermal
      ablation lesions, as evidenced by an acute ischemic infarction on MRI and
      histology, and hemorrhagic lesions, associated with inertial cavitation. Passive
      cavitation signals exhibited 3 main patterns identified as follows: no
      cavitation, stable cavitation, and inertial cavitation. Low-power and longer
      sonications induced only thermal lesions, with a peak temperature threshold for
      lesioning of 53 degrees C. Hemorrhagic lesions occurred only with high-power and
      shorter sonications. The sizes of the hemorrhages measured on macroscopic
      histological examinations correlated with the intensity of the cavitation
      activity (R2 = 0.74). The acoustic cavitation activity detected by the passive
      cavitation detectors exhibited a threshold of 0.09 V.Hz for the occurrence of
      hemorrhages. CONCLUSIONS: This work demonstrates that 220-kHz ultrasound is
      capable of inducing a thermal lesion in the brain of living swines without
      hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a
      thermal lesion, it seems that low-power, long-duration sonication is less likely
      to cause hemorrhage and may be safer. Although further study is needed to
      decrease the likelihood of ischemic infarction associated with the 220-kHz
      ultrasound, the threshold established in this work may allow for the detection
      and prevention of deleterious cavitations.

PMID- 25380107
TI  - Hypertonic saline reduces cumulative and daily intracranial pressure burdens
      after severe traumatic brain injury.
AB  - OBJECT: Increased intracranial pressure (ICP) in patients with traumatic brain
      injury (TBI) is associated with a higher mortality rate and poor outcome.
      Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but
      it is unclear which one is more effective. Here, the authors compare the effect
      of mannitol versus HTS on lowering the cumulative and daily ICP burdens after
      severe TBI. METHODS: The Brain Trauma Foundation TBI-trac New York State database
      was used for this retrospective study. Patients with severe TBI and intracranial
      hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS,
      were included. Patients in the 2 groups were individually matched for Glasgow
      Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of
      hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing
      or erroneous data were excluded. Cumulative and daily ICP burdens were used as
      primary outcome measures. The cumulative ICP burden was defined as the total
      number of days with an ICP of > 25 mm Hg, expressed as a percentage of the total
      number of days of ICP monitoring. The daily ICP burden was calculated as the mean
      daily duration of an ICP of > 25 mm Hg, expressed as the number of hours per day.
      The numbers of intensive care unit (ICU) days, numbers of days with ICP
      monitoring, and 2-week mortality rates were also compared between the groups. A 2
      sample t-test or chi-square test was used to compare independent samples. The
      Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing
      matched samples. RESULTS: A total of 35 patients who received only HTS and 477
      who received only mannitol after severe TBI were identified. Eight patients in
      the HTS group were excluded because of erroneous or missing data, and 2 other
      patients did not have matches in the mannitol group. The remaining 25 patients
      were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS
      as bolus therapy. All 25 patients in the mannitol group received 20% mannitol.
      The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and
      the mean (+/- SD) daily ICP burden (0.3 +/- 0.6 hours/day [HTS] vs 1.3 +/- 1.3
      hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The
      mean (+/- SD) number of ICU days was significantly lower in the HTS group than in
      the mannitol group (8.5 +/- 2.1 vs 9.8 +/- 0.6, respectively; p = 0.004), whereas
      there was no difference in the numbers of days of ICP monitoring (p = 0.09).
      There were no significant differences between the cumulative median doses of HTS
      and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group,
      but the difference was not statistically significant (p = 0.56). CONCLUSIONS: HTS
      given as bolus therapy was more effective than mannitol in lowering the
      cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had
      significantly lower number of ICU days. The 2-week mortality rates were not
      statistically different between the 2 groups.

PMID- 25380108
TI  - Editorial: industry-sponsored research.

PMID- 25380109
TI  - Gruber's ligament as a useful landmark for the abducens nerve in the transnasal
      approach.
AB  - OBJECT: Extended endoscopic transnasal surgeries for skull base lesions have
      recently been performed. Some expert surgeons have attempted to remove tumors
      such as chordomas, meningiomas, and pituitary adenomas in the clival region using
      the transnasal approach and have reported abducens nerve injury as a common
      complication. There have been many microsurgical anatomical studies of the
      abducens nerve, but none of these studies has described an anatomical landmark of
      the abducens nerve in the transnasal approach. In this study the authors used
      cadaver dissections to describe Gruber's ligament as the most reliable landmark
      of the abducens nerve in the transnasal transclival view. METHODS: The
      petroclival segment of the abducens nerve was dissected in the interdural space
      which is also called Dorello's canal, the petroclival venous gulf, or the
      sphenopetroclival venous confluence-using the transnasal approach in 20 specimens
      obtained from 10 adult cadaveric heads. RESULTS: The petroclival segment of the
      abducens nerve clearly crossed and attached to Gruber's ligament in the
      interdural space, as noted in the transnasal view. The average length of the
      dural porus to the intersection on the abducens nerve was 5.2 +/- 1.0 mm. The
      length of the posterior clinoid process (PCP) to the intersection on Gruber's
      ligament was 6.4 +/- 2.6 mm. The average width of Gruber's ligament at the
      midsection was 1.6 +/- 0.5 mm. CONCLUSIONS: Gruber's ligament is considered a
      useful landmark, and it is visible in most adults. Thus, surgeons can find the
      abducens nerve safely by visualizing inferolaterally along Gruber's ligament from
      the PCP.

PMID- 25380110
TI  - Hyperprolactinemia due to spontaneous intracranial hypotension.
AB  - OBJECT Spontaneous intracranial hypotension is an increasingly recognized cause
      of headaches. Pituitary enlargement and brain sagging are common findings on MRI
      in patients with this disorder. The authors therefore investigated pituitary
      function in patients with spontaneous intracranial hypotension. METHODS Pituitary
      hormones were measured in a group of 42 consecutive patients with spontaneous
      intracranial hypotension. For patients with hyperprolactinemia, prolactin levels
      also were measured following treatment. Magnetic resonance imaging was performed
      prior to and following treatment. RESULTS The study group consisted of 27 women
      and 15 men with a mean age at onset of symptoms of 52.2 +/- 10.7 years (mean +/-
      SD; range 17-72 years). Hyperprolactinemia was detected in 10 patients (24%),
      ranging from 16 ng/ml to 96.6 ng/ml in men (normal range 3-14.7 ng/ml) and from
      31.3 ng/ml to 102.5 ng/ml in women (normal range 3.8-23.2 ng/ml). In a
      multivariate analysis, only brain sagging on MRI was associated with
      hyperprolactinemia. Brain sagging was present in 60% of patients with
      hyperprolactinemia and in 19% of patients with normal prolactin levels (p =
      0.02). Following successful treatment of the spontaneous intracranial
      hypotension, hyperprolactinemia resolved, along with normalization of brain MRI
      findings in all 10 patients. CONCLUSIONS Spontaneous intracranial hypotension is
      a previously undescribed cause of hyperprolactinemia. Brain sagging causing
      distortion of the pituitary stalk (stalk effect) may be responsible for the
      hyperprolactinemia. 

PMID- 25380111
TI  - Frameless robotic stereotactic biopsies: a consecutive series of 100 cases.
AB  - OBJECT: Stereotactic biopsy procedures are an everyday part of neurosurgery. The
      procedure provides an accurate histological diagnosis with the least possible
      morbidity. Robotic stereotactic biopsy needs to be an accurate, safe, frameless,
      and rapid technique. This article reports the clinical results of a series of 100
      frameless robotic biopsies using a Medtech ROSA device. METHODS: The authors
      retrospectively analyzed their first 100 frameless stereotactic biopsies
      performed with the robotic ROSA device: 84 biopsies were performed by frameless
      robotic surface registration, 7 were performed by robotic bone fiducial marker
      registration, and 9 were performed by scalp fiducial marker registration.
      Intraoperative flat-panel CT scanning was performed concomitantly in 25 cases.
      The operative details of the robotic biopsies, the diagnostic yield, and
      mortality and morbidity data observed in this series are reported. RESULTS: A
      histological diagnosis was established in 97 patients. No deaths or permanent
      morbidity related to surgery were observed. Six patients experienced transient
      neurological worsening. Six cases of bleeding within the lesion or along the
      biopsy trajectory were observed on postoperative CT scans but were associated
      with transient clinical symptoms in only 2 cases. Stereotactic surgery was
      performed with patients in the supine position in 93 cases and in the prone
      position in 7 cases. The use of fiducial markers was reserved for posterior fossa
      biopsy via a transcerebellar approach, via an occipital approach, or for
      pediatric biopsy. CONCLUSIONS: ROSA frameless stereotactic biopsies appear to be
      accurate and safe robotized frameless procedures.

PMID- 25380112
TI  - Smoking is not associated with recurrence and retreatment of intracranial
      aneurysms after endovascular coiling.
AB  - OBJECT: Tobacco smoking is one of the most important risk factors for the
      formation of intracranial aneurysms and for aneurysmal subarachnoid hemorrhages.
      Smoking has also been suggested to contribute to the recurrence of aneurysms
      after endovascular coiling. To improve the understanding of the impact of smoking
      on long-term outcomes after coil embolization of intracranial aneurysms, the
      authors studied a consecutive contemporary series of patients treated at their
      institution. The aims of this study were to determine whether smoking is an
      independent risk factor for aneurysm recurrence and retreatment after
      endovascular coiling. METHODS: All patients who had received an intrasaccular
      coil embolization of an intracranial aneurysm, who had undergone a follow-up
      imaging exam at least 6 months later, and whose smoking history had been recorded
      from January 2005 through December 2012 were included in this study. Patients
      were stratified according to smoking status into 3 groups: 1) never a smoker, 2)
      current smoker (smoked at the time of treatment), and 3) former smoker (quit
      smoking before treatment). The 2 primary outcomes studied were aneurysm
      recurrence and aneurysm retreatment after treatment for endovascular aneurysms.
      Kruskal-Wallis and chi-square tests were used to test statistical significance of
      differences in the rates of aneurysm recurrence, retreatment, or of both among
      the 3 groups. A multivariate logistic regression analysis controlling for smoking
      status and for several characteristics of the aneurysm was also performed.
      RESULTS: In total, 384 patients with a combined total of 411 aneurysms were
      included in this study. The aneurysm recurrence rate was not significantly
      associated with smoking: both former smokers (OR 1.00, 95% CI 0.61-1.65; p =
      0.99) and current smokers (OR 0.58, 95% CI 0.31-1.09; p = 0.09) had odds of
      recurrence that were similar to those who were never smokers. Former smokers (OR
      0.78, 95% CI 0.46-1.35; p = 0.38) had odds of retreatment similar to those of
      never smokers, and current smokers had a lower odds of undergoing retreatment (OR
      0.44, 95% CI 0.21-0.91; p = 0.03) than never smokers. Moreover, an analysis
      adjusting for aneurysm rupture, diameter, and initial occlusion showed that
      former smokers (OR 0.65, 95% CI 0.33-1.28; p = 0.21) and current smokers (OR
      1.04, 95% CI 0.60-1.81; p = 0.88) had odds of aneurysm recurrence similar to
      those who were never smokers. Adjusting the analysis for aneurysm rupture,
      diameter, and occlusion showed that both former smokers (OR 0.49, 95% CI 0.23
      1.05; p = 0.07) and current smokers (OR 0.82, 95% CI 0.46-1.46; p = 0.50) had
      odds of retreatment similar to those of patients who were never smokers.
      CONCLUSIONS: The results show that smoking was not an independent risk factor for
      aneurysm recurrence and aneurysm retreatment among patients receiving
      endovascular treatment for intracranial aneurysms at the authors' institution.
      Nonetheless, patients with intracranial aneurysms should continue to be counseled
      about the risks of tobacco smoking.

PMID- 25380113
TI  - William H. Feindel (1918-2014).
AB  - William Howard Feindel (1918-2014) was one of the world's most distinguished
      neurosurgeons and a brilliant neuroscientist. As the Montreal Neurological
      Institute's third director, having succeeded Theodore Rasmussen and Wilder
      Penfield, he proved to be a visionary medical and scientific administrator. His
      keen interests in epilepsy and brain imaging were enhanced by a passion for
      medical history. Students and young people invariably gravitated to Dr. Feindel;
      he was a kind, patient, thoughtful, intelligent, and caring mentor who was never
      too busy for them. A pioneer in his own right, Dr. Feindel linked our modern
      neurosurgical world with the legacy of the first generations of important
      neurosurgeons and neuroscientists. 

PMID- 25380114
TI  - Petroclival meningiomas resected via a combined transpetrosal approach: surgical
      outcomes in 60 cases and a new scoring system for clinical evaluation.
AB  - OBJECT: Petroclival meningiomas are among the most challenging intracranial
      tumors to treat surgically. Many skull base approaches have been described to
      improve resection and decrease patient morbidity. The authors undertook this
      study to evaluate the results of their treatment of petroclival meningiomas using
      objective measurements of tumor volume and a new impairment scoring system to
      assess neurological symptoms that severely affect the patient's quality of life,
      such as impairment of swallowing and speaking, motor function, and consciousness
      and communication. METHODS: Between January 1990 and December 2009, the authors
      used a combined transpetrosal approach to treat 60 patients with benign (WHO
      Grade I) petroclival meningiomas. In this retrospective study, all 60 cases were
      analyzed in detail with regard to tumor volume, extent of resection (EOR), long
      term tumor control, neurological outcome, and the patient condition. In addition,
      patients were divided into 2 groups according to the period during which the
      surgery was performed: the early group, from 1990 to 1999, and the late group,
      from 2000 to 2009. A new scoring system, the petroclival meningioma impairment
      scale (PCMIS), was created for quantitative assessment of 8 categories of
      neurological functions, with scores assigned in each category according to the
      level of disability and its impact on the patient. The PCMIS was used
      preoperatively, at 3 months after surgery, and at the time of the last follow-up
      examination, and the results for the 2 groups were compared. RESULTS: There were
      24 cases in the early group (1990-1999), and the mean duration of follow-up was
      149.3 months. The mean EOR was 96.1%, and good long-term tumor control was
      obtained in 22 patients (91.7%). One of patients died because of a postoperative
      complication in the perioperative period. The PCMIS improved in 3 patients
      (12.5%), remained stable in 1 (4.2%), and worsened in 20 (83.3%). There were 36
      cases in the late group (2000-2009), and the mean duration of follow-up was 77.9
      months. The mean EOR was 92.7%, and good long-term tumor control was obtained in
      34 patients (94.4%). The PCMIS score improved in 23 patients (63.9%), remained
      stable in 5 (13.9%), and worsened in 8 (22.2%). CONCLUSIONS: The combined
      transpetrosal approach has provided satisfactory functional improvements and
      excellent tumor control for patients with petroclival meningiomas. The PCMIS
      provides a specific tool for quantitative assessment of the patient's state.

PMID- 25380115
TI  - Primary glioblastoma of the trigeminal nerve root entry zone: case report.
AB  - Gliomas of the cranial nerve root entry zone are rare clinical entities. There
      have been 11 reported cases in the literature, including only 2 glioblastomas.
      The authors report the case of a 67-year-old man who presented with isolated
      facial numbness and was found to have a glioblastoma involving the trigeminal
      nerve root entry zone. After biopsy the patient completed treatment with
      conformal radiation and concomitant temozolomide, and at 23 weeks after surgery
      he demonstrated symptom progression despite the treatment described. This is the
      first reported case of a glioblastoma of the trigeminal nerve root entry zone. 

PMID- 25380116
TI  - A novel acrosomal protein, IQCF1, involved in sperm capacitation and the acrosome
      reaction.
AB  - On the basis of the unknown tags in the mature human sperm serial analysis of
      gene expression library constructed by our laboratory, some transcripts were
      cloned, including Iqcf1 (IQ motif containing F1). To investigate the function of
      sperm-retained Iqcf1 in spermatogenesis and fertilization of mice, we
      investigated the spatial and temporal expression of IQCF1. By using the
      (transcription activator-like effector nuclease) strategy, Iqcf1-knockout mice
      were produced, and the phenotypes of the Iqcf1(-/-) mice were analyzed. The
      results showed that IQCF1 was localized in the acrosome of spermatozoa and
      spermatids; the expression of IQCF1 in testes was associated with spermatogenic
      capacity. The Iqcf1(-/-) mice were significantly less fertile than the wild-type
      mice (p = 0.0057) because of reduced sperm motility (p = 0.0094) and the acrosome
      reaction (AR) (p = 0.0093). In spermatozoa, IQCF1 interacted with calmodulin
      (CaM) and possibly participated in the tyrosine phosphorylation of sperm proteins
      during capacitation. In conclusion, a newly identified acrosomal protein, IQCF1,
      is closely related to sperm capacitation and AR; in particular, it is involved in
      tyrosine phosphorylation of sperm proteins through interaction with CaM. Research
      into the function of IQCF1 during fertilization could facilitate the
      investigation of the molecular mechanism of capacitation, which is unclear.

PMID- 25380117
TI  - Auditory research at the University of Memphis: faculty and students working
      together.

PMID- 25380118
TI  - Objective information-theoretic algorithm for detecting brainstem-evoked
      responses to complex stimuli.
AB  - BACKGROUND: The scalp-recorded frequency-following response (FFR), an auditory
      evoked potential with putative neural generators in the rostral brainstem,
      provides a robust representation of the neurophysiologic encoding of complex
      stimuli. The FFR is rapidly becoming a valuable tool for understanding the neural
      transcription of speech and music, language-related processing disorders, and
      brain plasticity at initial stages of the auditory pathway. Despite its potential
      clinical and empirical utility, determining the presence of a response is still
      dependent on the subjective interpretation by an experimenter/clinician. PURPOSE:
      The purpose of the present work was to develop and validate a fully objective
      procedure for the automatic detection of FFRs elicited by complex auditory
      stimuli, including speech. RESEARCH DESIGN: Mutual information (MI) was computed
      between the spectrographic representation of neural FFRs and their evoking
      acoustic stimuli to quantify the amount of shared time-frequency information
      between electrophysiologic responses and stimulus acoustics. To remove human
      subjectivity associated with typical response evaluation, FFRs were first
      simulated at known signal-to-noise ratios using a computational model of the
      auditory periphery. The MI at which model FFRs contained +3 dB Signal-to-noise
      ratio was taken as the criterion threshold (thetaMI) for the presence of a
      response. thetaMI was then applied as a binary classifier on actual
      neurophysiologic responses recorded previously in human participants (n = 35).
      Sham recordings, in which no stimulus was presented to participants, allowed us
      to determine the receiver operating characteristics of the MI metric and the
      capabilities of the algorithm to segregate true evoked responses from sham
      recordings. RESULTS: RESULTS showed high overall accuracy (93%) in the metric's
      ability to identify true responses from sham recordings. The metric's overall
      performance was considerably better than trained human observers who, on average,
      accurately identified only ~75% of the true neural responses. Complementary
      results were found in the metric's receiver operating characteristic test
      performance characteristics with a sensitivity and specificity of 97% and 85%,
      respectively. Additionally, MI increased monotonically and was asymptotic with
      increasing trials (i.e., sweeps) contributing to the averaged FFR and, thus, can
      be used as a stopping criteria for signal averaging. CONCLUSIONS: The present
      results demonstrate that the mutual information between a complex acoustic
      stimulus and its corresponding brainstem response can provide a completely
      objective and robust method for automated FFR detection. Application of the MI
      metric to evoked potential speech audiometry testing may provide clinicians with
      a more robust tool to quantitatively evaluate the presence and quality of speech
      evoked brainstem responses ultimately minimizing subjective interpretation and
      human error.

PMID- 25379911
TI  - Search for scalar diphoton resonances in the mass range 65-600 GeV with the ATLAS
      detector in pp collision data at ?s=8 TeV.
AB  - A search for scalar particles decaying via narrow resonances into two photons in
      the mass range 65-600 GeV is performed using 20.3  fb(-1) of ?s 8 TeV pp
      collision data collected with the ATLAS detector at the Large Hadron Collider.
      The recently discovered Higgs boson is treated as a background. No significant
      evidence for an additional signal is observed. The results are presented as
      limits at the 95% confidence level on the production cross section of a scalar
      boson times branching ratio into two photons, in a fiducial volume where the
      reconstruction efficiency is approximately independent of the event topology. The
      upper limits set extend over a considerably wider mass range than previous
      searches.

PMID- 25380119
TI  - Development of the Device-Oriented Subjective Outcome (DOSO) scale.
AB  - BACKGROUND: The empiric basis for this work is derived from previous research
      completed in our laboratory and published in 2005 and 2007. The previous work
      suggested that self-report hearing aid outcomes can be viewed as device oriented
      or wearer oriented. Furthermore, compared with wearer-oriented outcomes, device
      oriented outcomes were more independent of personality variables. PURPOSE: The
      purpose of this study was to develop a device-oriented questionnaire to measure
      self-report hearing aid outcomes. RESEARCH DESIGN: Design was a descriptive study
      in which 140 potential questionnaire items were evaluated and a questionnaire was
      devised. STUDY SAMPLE: A total of 306 adult hearing aid wearers participated: 189
      were clinical patients and 117 were participants in hearing aid field trials.
      DATA COLLECTION AND ANALYSIS: Some items and some participants were removed
      because of insufficient responses. The final dataset included 295 participants
      and 66 items. Response data were subjected to exploratory principal component
      analysis with orthogonal rotation. Six components, explaining 64% of the
      variance, were retained. Item statistics were examined. RESULTS: Six subscales
      were identified. Long and short forms of the questionnaire were developed. There
      are two equivalent versions of the short form. CONCLUSIONS: The Device-Oriented
      Subjective Outcome (DOSO) questionnaire is suitable for quantifying subjective
      hearing aid outcomes in both research and clinical settings. The DOSO is
      especially suited for comparing outcomes with different hearing aids. Future
      research is needed to cross-validate the results, determine retest consistency,
      and to explore the extent to which data from the DOSO is independent of
      personality.

PMID- 25380120
TI  - Recording and evaluation of an American dialect version of the Four Alternative
      Auditory Feature test.
AB  - BACKGROUND: The Four Alternative Auditory Feature test (FAAF) is a word-based
      closed-set speech recognition test. Because the original test materials were
      recorded in British English dialect, it is not appropriate for use in the United
      States. PURPOSE: The purpose of this study was to produce an American dialect
      FAAF (AFAAF). RESEARCH DESIGN: The AFAAF materials spoken by a native American
      English speaking male were recorded and digitally edited. In the validation
      study, the AFAAF was administered monaurally at five signal-to-noise ratios
      (SNRs) in both ears for each listener. STUDY SAMPLE: A total of 20 young adults
      with normal hearing participated in the validation study. DATA COLLECTION AND
      ANALYSIS: For each participant, speech recognition scores were collected in one
      session. The speech level was fixed at 70 dB SPL and the steady-state talker
      matched noise level was varied, resulting in five SNRs from -15 to -5 dB. One
      full list (80 words) was used for each SNR. For each participant, a performance
      intensity (PI) function was fit to the discrete mean percent correct scores for
      the five SNRs according to a best-fit, three-parameter sigmoid function. In
      addition, scores for the left and right ears were compared to examine test-retest
      reliability. RESULTS: RESULTS show that the slope of the PI function is 6% per
      dB, the mean test-retest difference scores for the five SNRs are within 3
      rationalized arcsine units (rau), and the 95% critical difference for the 80-word
      scores is 12 rau. Compared with the FAAF, the slope of the PI function for the
      AFAAF is slightly less steep. Test-retest reliability of the AFAAF is at least
      equal to that of the FAAF. CONCLUSIONS: It is concluded that the AFAAF is similar
      but not identical to the FAAF. The AFAAF is now available for measuring speech
      recognition performance in listeners who use American English as a native
      language.

PMID- 25380121
TI  - Modeling DPOAE input/output function compression: comparisons with hearing
      thresholds.
AB  - BACKGROUND: Basilar membrane input/output (I/O) functions in mammalian animal
      models are characterized by linear and compressed segments when measured near the
      location corresponding to the characteristic frequency. A method of studying
      basilar membrane compression indirectly in humans involves measuring distortion
      product otoacoustic emission (DPOAE) I/O functions. Previous research has linked
      compression estimates from behavioral growth-of-masking functions to hearing
      thresholds. PURPOSE: The aim of this study was to compare compression estimates
      from DPOAE I/O functions and hearing thresholds at 1 and 2 kHz. RESEARCH DESIGN:
      A prospective correlational research design was performed. The relationship
      between DPOAE I/O function compression estimates and hearing thresholds was
      evaluated with Pearson product-moment correlations. STUDY SAMPLE: Normal-hearing
      adults (n = 16) aged 22-42 yr were recruited. DATA COLLECTION AND ANALYSIS: DPOAE
      I/O functions (L2 = 45-70 dB SPL) and two-interval forced-choice hearing
      thresholds were measured in normal-hearing adults. A three-segment linear
      regression model applied to DPOAE I/O functions supplied estimates of compression
      thresholds, defined as breakpoints between linear and compressed segments and the
      slopes of the compressed segments. Pearson product-moment correlations between
      DPOAE compression estimates and hearing thresholds were evaluated. RESULTS: A
      high correlation between DPOAE compression thresholds and hearing thresholds was
      observed at 2 kHz, but not at 1 kHz. Compression slopes also correlated highly
      with hearing thresholds only at 2 kHz. CONCLUSIONS: The derivation of cochlear
      compression estimates from DPOAE I/O functions provides a means to characterize
      basilar membrane mechanics in humans and elucidates the role of compression in
      tone detection in the 1-2 kHz frequency range.

PMID- 25380123
TI  - Normative data for the Maryland CNC Test.
AB  - BACKGROUND: The Maryland consonant-vowel nucleus-consonant (CNC) Test is
      routinely used in Veterans Administration medical centers, yet there is a paucity
      of published normative data for this test. PURPOSE: The purpose of this study was
      to provide information on the means and distribution of word-recognition scores
      on the Maryland CNC Test as a function of degree of hearing loss for a veteran
      population. RESEARCH DESIGN: A retrospective, descriptive design was conducted.
      STUDY SAMPLE: The sample consisted of records from veterans who had Compensation
      and Pension (C&P) examinations at a Veterans Administration medical center (N =
      1,760 ears). DATA COLLECTION AND ANALYSIS: Audiometric records of veterans who
      had C&P examinations during a 10 yr period were reviewed, and the pure-tone
      averages (PTA4) at four frequencies (1000, 2000, 3000, and 4000 Hz) were
      documented. The maximum word-recognition score (PBmax) was determined from the
      performance-intensity functions obtained using the Maryland CNC Test.
      Correlations were made between PBmax and PTA4. RESULTS: A wide range of word
      recognition scores were obtained at all levels of PTA4 for this population. In
      addition, a strong negative correlation between the PBmax and the PTA4 was
      observed, indicating that as PTA4 increased, PBmax decreased. Word-recognition
      scores decreased significantly as hearing loss increased beyond a mild hearing
      loss. Although threshold was influenced by age, no statistically significant
      relationship was found between word-recognition score and the age of the
      participants. CONCLUSIONS: RESULTS from this study provide normative data in
      table and figure format to assist audiologists in interpreting patient results on
      the Maryland CNC test for a veteran population. These results provide a
      quantitative method for audiologists to use to interpret word-recognition scores
      based on pure-tone hearing loss.

PMID- 25380125
TI  - Effect of methyl-branched fatty acids on the structure of lipid bilayers.
AB  - Methyl-branched fatty acids are widespread in prokaryotic membranes. Although
      anteiso and iso branching (that is on the antepenultimate and penultimate
      carbons) and the presence of multiple methyl branches in the phytanoyl chain are
      known to modify the thermotropic behavior and enhance the fluidity of lipid
      bilayers, little is known about the effect of methyl branching on the structure
      of lipid bilayers. In this study, molecular dynamics simulations are used to
      examine systematically the impact of one or more methyl branches at different
      positions along the sn-1 palmitoyl chain on the structural properties of a 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayer. It is found that
      methyl branching reduces lipid condensation, decreases the bilayer thickness, and
      lowers chain ordering. Branching also results in the formation of kinks at the
      branching point, thereby enhancing the fluidity of lipid bilayers. Furthermore,
      this effect varies in a methyl-position-dependent fashion. In the case of
      polymethylated chains, the simulations suggest that if the gap between the methyl
      groups is sufficient (two or three carbons), the effects of the methyl branches
      are additive and equivalent to the combined effect of the corresponding
      monomethyl-branched lipids. 

PMID- 25380122
TI  - Challenges in ototoxicity monitoring in the pediatric oncology population.
AB  - BACKGROUND: Platinum-based chemotherapy and cranial radiation are effective
      treatment options commonly prescribed for a variety of childhood cancers. These
      therapies can, and often do, result in early- and late-onset adverse health
      effects such as hearing loss. Undetected hearing loss is particularly concerning
      in young children developing speech and language skills and can negatively affect
      academic achievement and the psychosocial well-being of both young and older
      children. Early detection of hearing loss in pediatric oncology patients and
      early intervention are critical to help these patients succeed in achieving these
      developmental milestones. PURPOSE: The primary goal of this study was to create a
      tutorial for audiologists concerning the monitoring of ototoxicity in the
      pediatric oncology population. Monitoring hearing for children receiving
      potentially ototoxic cancer treatments presents special issues and challenges for
      audiologists. This tutorial will orient the reader to these special issues and
      challenges, and potential solutions will be proposed. DESIGN: This tutorial is
      organized into sections, including an overview of platinum compound and cranial
      radiation treatments commonly used to treat pediatric cancer, modifications of
      the test battery required to appropriately monitor for ototoxic hearing loss in
      children, a proposal for a monitoring protocol, and descriptions of the grading
      scales that are frequently used by oncologists to determine the severity of
      ototoxic hearing loss. CONCLUSIONS: Identification of ototoxicity is crucial in
      children receiving cancer treatments because of the impact that acquired hearing
      loss has on social and educational outcomes in the developing child. Monitoring
      hearing in children presents challenges that are unique to this population. Much
      effort has been put forth in developing and validating the International Society
      of Pediatric Oncology ototoxicity grading scale for international use in
      reporting auditory outcomes in clinical trials. In the future, the development of
      standardized monitoring protocols will assist audiologists in providing optimal
      care to children treated for cancer.

PMID- 25380126
TI  - Severe neonatal presentation of Kleefstra syndrome in a patient with hypoplastic
      left heart syndrome and 9q34.3 microdeletion.
AB  - BACKGROUND: Kleefstra syndrome arises from haploinsufficiency of EHMT1 caused by
      either microdeletions at 9q34.3 or intragenic mutations. Patients with Kleefstra
      syndrome have multisystem involvement including intellectual disability,
      hypotonia, and characteristic facial features. METHODS: We report on the severe
      neonatal presentation of the first case of Kleefstra syndrome associated with
      hypoplastic left heart syndrome and multicystic renal disease in a patient with a
      9q34.3 microdeletion. RESULTS: Array-CGH analysis revealed a 2.1 Mb deletion at
      9q34.3, including EHMT1 and NOTCH1. CONCLUSION: Kleefstra syndrome is a
      multisystem disorder with a high frequency of congenital heart disease and less
      frequently, renal defects. Mortality has rarely been documented, particularly in
      infancy. Based on the present case and the extant literature, a routine
      echocardiogram and renal ultrasound should be ordered in all cases of Kleefstra
      syndrome. The cardiac changes seen in this patient could be the result of the
      haploinsufficiency of EHMT1, NOTCH1, or their combined effect.

PMID- 25380128
TI  - Mortality after distal radius fracture in men and women aged 50 years and older
      in southern Norway.
AB  - Increased mortality rates in patients sustaining hip and vertebral fractures are
      well documented; however in distal radius fracture patients the results are
      conflicting. The aim of this study was to examine short- and long-term mortality
      in distal radius fracture patient in comparison with the background population.
      Patients aged >= 50 years with distal radius fracture living in Southern Norway
      who suffered a fracture in the two year period 2004 and 2005 were included in the
      study. The mortality risk of the standard Norwegian population was used to
      calculate the standardized mortality ratio (SMR). The number of distal radius
      fractures was 883 (166 men and 717 women). Mean age was 69 years (men 65 years
      and women 70 years). After one year the overall mortality rate was 3.4% (men 5.4%
      and women 2.9%) and after five years 4.6% (men 4.0% and women 4.8%). The SMR for
      men and women compared to the Norwegian population for the first year was 1.6
      (95% confidence interval (CI): 0.6, 2.7) and 0.9 (95% CI: 0.4, 1.2),
      respectively, and after five years 1.7 (95% CI: 0.3, 3.0) and 2.0 (95% CI: 1.2,
      2.7). Stratified on age groups (50-70 and >70 years) an increased SMR was only
      seen in female patients aged >70 years five years after the fracture (SMR: 1.9,
      95% CI: 1.1, 2.6). In conclusion, increased SMR was found in female patients aged
      >70 years five years after the distal radius fracture, but not in men or in women
      younger than 70 years.

PMID- 25380127
TI  - Culture and Characterization of Oral Mucosal Epithelial Cells on a Fibrin Gel for
      Ocular Surface Reconstruction.
AB  - AIM OF THE STUDY: To develop a clinical grade fibrin gel for the culture of oral
      mucosal epithelial cells (OMEC) intended for ocular surface reconstruction in the
      treatment of limbal stem cell deficiency (LSCD). MATERIALS AND METHODS:
      Transparent fibrin gels composed of fibrinogen and thrombin were developed for
      the culture of epithelial cells. Oral mucosa was harvested from the buccal region
      of healthy volunteers and cultured as explants on fibrin gels. Tranexamic acid
      (TA), a clinically approved anti-fibrinolytic agent was added to prevent the
      fibrin gel from digesting due to cellular activity. The gels were stained for
      p63alpha (as a marker of poorly differentiated epithelial cells), CK19, CK13 and
      CK3 (expressed by OMEC). Epithelial cell stratification was observed using
      hematoxylin-eosin staining. RESULTS: Addition of TA prevented gels from
      dissolving during the culture period. OMEC proliferated on the fibrin gel and
      attained confluence over a 2-week period (+/-2 d) and exhibited a typical
      epithelial, cobblestone morphology. Basal OMEC exhibited positive staining for
      p63alpha while the superficial cells exhibited positive staining for CK3. The
      cells expressed a strong immunoreactivity for CK19 and CK13 suggesting that they
      retained a normal oral epithelial phenotype. CONCLUSION: Fibrin gels, maintained
      in the presence of TA, to control the rate of substrate degradation, provide a
      more robust yet transparent substrate for the culture and transplantation of
      cultured OMEC. The fibrin gels are easily standardized, the components
      commercially available, and produced from clinically approved materials. The
      resulting stratified OMEC-derived epithelium displays characteristics similar to
      that of a human cornea, e.g. CK3 expression. The conventional dependence on a
      murine feeder layer for support of epithelial cells is unnecessary with this
      technique and hence, provides for an attractive alternative for treatment of
      LSCD.

PMID- 25380129
TI  - Enantioselective selenocyclization via dynamic kinetic resolution of seleniranium
      ions by hydrogen-bond donor catalysts.
AB  - Highly enantioselective selenocyclization reactions are promoted by the
      combination of a new chiral squaramide catalyst, a mineral acid, and an achiral
      Lewis base. Mechanistic studies reveal that the enantioselectivity originates
      from the dynamic kinetic resolution of seleniranium ions through anion-binding
      catalysis. 

PMID- 25380130
TI  - Performance of healthy subjects on an ecologically valid test for social
      cognition: the short, Dutch Version of The Awareness of Social Inference Test
      (TASIT).
AB  - The present paper addresses the psychometric quality of the shortened Dutch
      version of The Awareness of Social Inference Test (TASIT), a social cognition
      task comprising dynamic social interactions. Because the original TASIT required
      a rather long administration time, two shortened parallel forms were developed.
      Results showed that TASIT-short was feasible and that the two alternate forms
      were reasonably comparable in a group of neurologically healthy individuals (N =
      98). Also, the results confirmed the ecological validity of TASIT-short in this
      healthy group. The test appeared sensitive to brain injury as it differentiated
      between the healthy subjects and a group of patients with acquired brain injury
      (N = 16). On the basis of the present study we conclude that TASIT-short has
      added value to the assessment of social cognition in patients with acquired brain
      injury. 

PMID- 25380131
TI  - Stereospecific synthesis of 23-hydroxyundecylprodiginines and analogues and
      conversion to antimalarial premarineosins via a Rieske oxygenase catalyzed
      bicyclization.
AB  - Facile and highly efficient synthetic routes for the synthesis of (S)- and (R)-23
      hydroxyundecylprodiginines ((23S)-2, and (23R)-2), 23-ketoundecylprodiginine (3),
      and deuterium-labeled 23-hydroxyundecylprodiginine ([23-d]-2) have been
      developed. We demonstrated a novel Rieske oxygenase MarG catalyzed
      stereoselective bicyclization of (23S)-2 to premarineosin A (4), a key step in
      the tailoring process of the biosynthesis of marineosins, using a marG
      heterologous expression system. The synthesis of various A-C-ring functionalized
      prodiginines 32-41 was achieved to investigate the substrate promiscuity of MarG.
      The two analogues 32 and 33 exhibit antimalarial and cytotoxic activities
      stronger than those of the marineosin intermediate 2, against Plasmodium
      falciparum strains (CQ(S)-D6, CQ(R)-Dd2, and 7G8) and hepatocellular HepG2 cancer
      cell line, respectively. Feeding of 34-36 to Streptomyces venezuelae expressing
      marG led to production of novel premarineosins, paving a way for the production
      of marineosin analogues via a combinatorial synthetic/biosynthetic approach. This
      study presents the first example of oxidative bicyclization mediated by a Rieske
      oxygenase. 

PMID- 25380132
TI  - Differential responses of the antioxidant system of ametryn and clomazone
      tolerant bacteria.
AB  - The herbicides ametryn and clomazone are widely used in sugarcane cultivation,
      and following microbial degradation are considered as soil and water
      contaminants. The exposure of microorganisms to pesticides can result in
      oxidative damage due to an increase in the production of reactive oxygen species
      (ROS). This study investigated the response of the antioxidant systems of two
      bacterial strains tolerant to the herbicides ametryn and clomazone. Bacteria were
      isolated from soil with a long history of ametryn and clomazone application.
      Comparative analyses based on 16S rRNA gene sequences revealed that strain CC07
      is phylogenetically related to Pseudomonas aeruginosa and strain 4C07 to P.
      fulva. The two bacterial strains were grown for 14 h in the presence of separate
      and combined herbicides. Lipid peroxidation, reduced glutathione content (GSH)
      and antioxidant enzymes activities were evaluated. The overall results indicated
      that strain 4C07 formed an efficient mechanism to maintain the cellular redox
      balance by producing reactive oxygen species (ROS) and subsequently scavenging
      ROS in the presence of the herbicides. The growth of bacterium strain 4C07 was
      inhibited in the presence of clomazone alone, or in combination with ametryn, but
      increased glutathione reductase (GR) and glutathione S-transferase (GST)
      activities, and a higher GSH concentration were detected. Meanwhile, reduced
      superoxide dismutase (SOD), catalase (CAT) and GST activities and a lower
      concentration of GSH were detected in the bacterium strain CC07, which was able
      to achieve better growth in the presence of the herbicides. The results suggest
      that the two bacterial strains tolerate the ametryn and clomazone herbicides with
      distinctly different responses of the antioxidant systems. 

PMID- 25380133
TI  - Sperm flagellum volume determines freezability in red deer spermatozoa.
AB  - The factors affecting the inter-individual differences in sperm freezability is a
      major line of research in spermatology. Poor sperm freezability is mainly
      characterised by a low sperm velocity, which in turn is associated with low
      fertility rates in most animal species. Studies concerning the implications of
      sperm morphometry on freezability are quite limited, and most of them are based
      on sperm head size regardless of the structural parts of the flagellum, which
      provides sperm motility. Here, for the first time, we determined the volumes of
      the flagellum structures in fresh epididymal red deer spermatozoa using a
      stereological method under phase contrast microscopy. Sperm samples from thirty
      three stags were frozen and classified as good freezers (GF) or bad freezers (BF)
      at two hours post-thawing using three sperm kinetic parameters which are strongly
      correlated with fertility in this species. Fourteen stags were clearly identified
      as GF, whereas nineteen were BF. No significant difference in sperm head size
      between the two groups was found. On the contrary, the GF exhibited a lower
      principal piece volume than the BF (6.13 um3 vs 6.61 um3, respectively, p =
      0.006). The volume of the flagellum structures showed a strong negative
      relationship with post-thawing sperm velocity. For instance, the volume of the
      sperm principal piece was negatively correlated with sperm velocity at two hours
      post-thawing (r = -0.60; p<0.001). Our results clearly show that a higher volume
      of the sperm principal piece results in poor freezability, and highlights the key
      role of flagellum size in sperm cryopreservation success. 

PMID- 25380134
TI  - Predicting nucleosome positioning based on geometrically transformed Tsallis
      entropy.
AB  - As the fundamental unit of eukaryotic chromatin structure, nucleosome plays
      critical roles in gene expression and regulation by controlling physical access
      to transcription factors. In this paper, based on the geometrically transformed
      Tsallis entropy and two index-vectors, a valid nucleosome positioning information
      model is developed to describe the distribution of A/T-riched and G/C-riched
      dimeric and trimeric motifs along the DNA duplex. When applied to train the
      support vector machine, the model achieves high AUCs across five organisms, which
      have significantly outperformed the previous studies. Besides, we adopt the
      concept of relative distance to describe the probability of arbitrary DNA
      sequence covered by nucleosome. Thus, the average nucleosome occupancy profile
      over the S.cerevisiae genome is calculated. With our peak detection model, the
      isolated nucleosomes along genome sequence are located. When compared with some
      published results, it shows that our model is effective for nucleosome
      positioning. The index-vector component [Formula in text] is identified to be an
      important influencing factor of nucleosome organizations.

PMID- 25380135
TI  - Spiroacetals in the colonization behaviour of the coffee berry borer: a 'push
      pull' system.
AB  - Coffee berries are known to release several volatile organic compounds, among
      which is the spiroacetal, conophthorin, an attractant for the coffee berry borer
      Hypothenemus hampei. Elucidating the effects of other spiroacetals released by
      coffee berries is critical to understanding their chemo-ecological roles in the
      host discrimination and colonization process of the coffee berry borer, and also
      for their potential use in the management of this pest. Here, we show that the
      coffee berry spiroacetals frontalin and 1,6-dioxaspiro [4.5] decane (referred
      thereafter as brocain), are also used as semiochemicals by the coffee berry borer
      for host colonization. Bioassays and chemical analyses showed that crowding
      coffee berry borers from 2 to 6 females per berry, reduced borer fecundity, which
      appeared to correlate with a decrease in the emission rates of conophthorin and
      frontalin over time. In contrast, the level of brocain did not vary significantly
      between borer- uninfested and infested berries. Brocain was attractive at lower
      doses, but repellent at higher doses while frontalin alone or in a blend was
      critical for avoidance. Field assays with a commercial attractant comprising a
      mixture of ethanol and methanol (1 ? 1), combined with frontalin, confirmed the
      repellent effect of this compound by disrupting capture rates of H. hampei
      females by 77% in a coffee plantation. Overall, our results suggest that the
      levels of frontalin and conophthorin released by coffee berries determine the
      host colonization behaviour of H. hampei, possibly through a 'push-pull' system,
      whereby frontalin acts as the 'push' (repellent) and conophthorin acting as the
      'pull' (attractant). Furthermore, our results reveal the potential use of
      frontalin as a repellent for management of this coffee pest.

PMID- 25380137
TI  - Cells producing their own nemesis: understanding methylglyoxal metabolism.
AB  - Methylglyoxal, which is technically known as 2-oxopropanal or pyruvaldehyde,
      shows typical reactions of carbonyl compounds as it has both an aldehyde and a
      ketone functional group. It is an extremely cytotoxic physiological metabolite,
      which is generated by both enzymatic and nonenzymatic reactions. The deleterious
      nature of the compound is due to its ability to glycate and crosslink
      macromolecules like protein and DNA, respectively. However, despite having toxic
      effects on cellular processes, methylglyoxal retains its efficacy as an
      anticancer drug. Indeed, methylglyoxal is one of the well-known anticancer
      therapeutic agents used in the treatment. Several studies on methylglyoxal
      biology revolve around the manifestations of its inhibitory effects and toxicity
      in microbial growth and diabetic complications, respectively. Here, we have
      revisited the chronology of methylglyoxal research with emphasis on metabolism of
      methylglyoxal and implications of methylglyoxal production or detoxification on
      bacterial pathogenesis and disease progression.

PMID- 25380138
TI  - European society of contraception statement on contraception in obese women.
AB  - The obesity 'epidemic' continues to increase, mostly but not only in developed
      countries. As overweight and obese women are at an increased risk for venous
      thromboembolism (VTE) at baseline and at a much higher risk during pregnancy, it
      is essential to help these women to plan pregnancies carefully and to use
      contraceptives with a positive ratio of benefits versus risks. The Expert Group
      on hormonal and molecular contraception of the European Society of Contraception
      convened to review the existing evidence and propose recommendations to the
      prescribers in line with most recent studies and with the Medical Eligibility
      Criteria of the World Health Organisation.

PMID- 25380136
TI  - Systems level analysis and identification of pathways and networks associated
      with liver fibrosis.
AB  - Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and
      liver failure. Despite recent progress in understanding the mechanism of liver
      fibrosis, our knowledge of the molecular-level details of this disease is still
      incomplete. The elucidation of networks and pathways associated with liver
      fibrosis can provide insight into the underlying molecular mechanisms of the
      disease, as well as identify potential diagnostic or prognostic biomarkers.
      Towards this end, we analyzed rat gene expression data from a range of chemical
      exposures that produced observable periportal liver fibrosis as documented in
      DrugMatrix, a publicly available toxicogenomics database. We identified genes
      relevant to liver fibrosis using standard differential expression and co
      expression analyses, and then used these genes in pathway enrichment and protein
      protein interaction (PPI) network analyses. We identified a PPI network module
      associated with liver fibrosis that includes known liver fibrosis-relevant genes,
      such as tissue inhibitor of metalloproteinase-1, galectin-3, connective tissue
      growth factor, and lipocalin-2. We also identified several new genes, such as
      perilipin-3, legumain, and myocilin, which were associated with liver fibrosis.
      We further analyzed the expression pattern of the genes in the PPI network module
      across a wide range of 640 chemical exposure conditions in DrugMatrix and
      identified early indications of liver fibrosis for carbon tetrachloride and
      lipopolysaccharide exposures. Although it is well known that carbon tetrachloride
      and lipopolysaccharide can cause liver fibrosis, our network analysis was able to
      link these compounds to potential fibrotic damage before histopathological
      changes associated with liver fibrosis appeared. These results demonstrated that
      our approach is capable of identifying early-stage indicators of liver fibrosis
      and underscore its potential to aid in predictive toxicity, biomarker
      identification, and to generally identify disease-relevant pathways. 

PMID- 25380140
TI  - Emergence, evolution and scaling of online social networks.
AB  - Online social networks have become increasingly ubiquitous and understanding
      their structural, dynamical, and scaling properties not only is of fundamental
      interest but also has a broad range of applications. Such networks can be
      extremely dynamic, generated almost instantaneously by, for example, breaking
      news items. We investigate a common class of online social networks, the user
      user retweeting networks, by analyzing the empirical data collected from Sina
      Weibo (a massive twitter-like microblogging social network in China) with respect
      to the topic of the 2011 Japan earthquake. We uncover a number of algebraic
      scaling relations governing the growth and structure of the network and develop a
      probabilistic model that captures the basic dynamical features of the system. The
      model is capable of reproducing all the empirical results. Our analysis not only
      reveals the basic mechanisms underlying the dynamics of the retweeting networks,
      but also provides general insights into the control of information spreading on
      such networks. 

PMID- 25380142
TI  - Effective passivation of exfoliated black phosphorus transistors against ambient
      degradation.
AB  - Unencapsulated, exfoliated black phosphorus (BP) flakes are found to chemically
      degrade upon exposure to ambient conditions. Atomic force microscopy,
      electrostatic force microscopy, transmission electron microscopy, X-ray
      photoelectron spectroscopy, and Fourier transform infrared spectroscopy are
      employed to characterize the structure and chemistry of the degradation process,
      suggesting that O2 saturated H2O irreversibly reacts with BP to form oxidized
      phosphorus species. This interpretation is further supported by the observation
      that BP degradation occurs more rapidly on hydrophobic octadecyltrichlorosilane
      self-assembled monolayers and on H-Si(111) versus hydrophilic SiO2. For
      unencapsulated BP field-effect transistors, the ambient degradation causes large
      increases in threshold voltage after 6 h in ambient, followed by a ~ 10(3)
      decrease in FET current on/off ratio and mobility after 48 h. Atomic layer
      deposited AlOx overlayers effectively suppress ambient degradation, allowing
      encapsulated BP FETs to maintain high on/off ratios of ~ 10(3) and mobilities of
      ~ 100 cm(2) V(-1) s(-1) for over 2 weeks in ambient conditions. This work shows
      that the ambient degradation of BP can be managed effectively when the flakes are
      sufficiently passivated. In turn, our strategy for enhancing BP environmental
      stability will accelerate efforts to implement BP in electronic and
      optoelectronic applications.

PMID- 25380141
TI  - Anti-angiogenic effects of a mutant endostatin: a new prospect for treating
      retinal and choroidal neovascularization.
AB  - PURPOSE: Pathological fundus angiogenesis is a major cause of vision loss in
      retina diseases. Endostatin, a C-terminal fragment of collagen XVIII, is an
      endogenous anti-angiogenic protein. The present study aimed to investigate the in
      vitro and in vivo anti-angiogenic properties of two proteins: an N-terminal
      H1D/H3D mutant endostatin (M-ES) and a polyethylene glycol propionaldehyde (PEG)
      covalent M-ES (PEG-M-ES). METHODS: M-ES and PEG-M-ES properties were
      characterized in vitro using a zinc ion binding assay and a stability test.
      Activity assays, including migration, proliferation, and tube formation assays,
      were performed with human retinal microvascular endothelial cells (HRMECs) and
      human umbilical vein endothelial cells (HUVECs). Mouse oxygen-induced retinopathy
      (OIR) and choroidal neovascularization (CNV) models were used to evaluate in vivo
      anti-angiogenic effects. In addition, a rabbit model was used to study the
      retinal pharmacokinetic profile following an intravitreal injection. RESULTS: The
      results indicated that the H1D/H3D mutations of endostatin reduced the zinc
      binding capacity of M-ES and facilitated PEG covalent binding. PEG-M-ES was more
      stable and persisted longer in the retina compared with M-ES. The in vitro
      studies demonstrated that M-ES and PEG-M-ES inhibited HRMEC and HUVEC
      proliferation, migration, and tube formation more efficiently than ES. In vivo, a
      single intravitreal injection of M-ES and PEG-M-ES significantly decreased
      neovascularization in both the OIR and CNV animal models. CONCLUSION: The present
      study demonstrated for the first time that PEG-M-ES exhibits a long-term
      inhibitory effect on neovascularization in vitro and in vivo. These data suggest
      that PEG-M-ES may represent an innovative therapeutic strategy to prevent fundus
      neovascularization.

PMID- 25380143
TI  - Micromilling enhances iron bioaccessibility from wholegrain wheat.
AB  - Cereals constitute important sources of iron in human diet; however, much of the
      iron in wheat is lost during processing for the production of white flour. This
      study employed novel food processing techniques to increase the bioaccessibility
      of naturally occurring iron in wheat. Iron was localized in wheat by Perl's
      Prussian blue staining. Soluble iron from digested wheat flour was measured by a
      ferrozine spectrophotometric assay. Iron bioaccessibility was determined using an
      in vitro simulated peptic-pancreatic digestion, followed by measurement of
      ferritin (a surrogate marker for iron absorption) in Caco-2 cells. Light
      microscopy revealed that iron in wheat was encapsulated in cells of the aleurone
      layer and remained intact after in vivo digestion and passage through the
      gastrointestinal tract. The solubility of iron in wholegrain wheat and in
      purified wheat aleurone increased significantly after enzymatic digestion with
      Driselase, and following mechanical disruption using micromilling. Furthermore,
      following in vitro simulated peptic-pancreatic digestion, iron bioaccessibility,
      measured as ferritin formation in Caco-2 cells, from micromilled aleurone flour
      was significantly higher (52%) than from whole aleurone flour. Taken together our
      data show that disruption of aleurone cell walls could increase iron
      bioaccessibility. Micromilled aleurone could provide an alternative strategy for
      iron fortification of cereal products. 

PMID- 25380144
TI  - Teaching evidence-based medicine at complementary and alternative medicine
      institutions: strategies, competencies, and evaluation.
AB  - BACKGROUND: As evidence-based medicine (EBM) becomes a standard in health care,
      it is essential that practitioners of complementary and alternative medicine
      (CAM) become experts in searching and evaluating the research literature. In
      support of this goal, the National Institutes of Health (NIH) National Center for
      Complementary and Alternative Medicine (NCCAM) provided R25 funding to nine CAM
      colleges to develop individual programs focused on teaching EBM. An overarching
      goal of these research education grants has been to provide CAM faculty and
      students with the skills they need to apply a rigorous evidence-based perspective
      to their training and practice. METHODS/RESULTS: This paper reviews the
      competencies and teaching strategies developed and implemented to enhance
      research literacy at all nine R25-funded institutions. While each institution
      designed approaches suitable for its research culture, the guiding principles
      were similar: to develop evidence-informed skills and knowledge, thereby helping
      students and faculty to critically appraise evidence and then use that evidence
      to guide their clinical practice. Curriculum development and assessment included
      faculty-driven learning activities and longitudinal curricular initiatives to
      encourage skill reinforcement and evaluate progress. CONCLUSION: As the field of
      integrative medicine matures, the NIH-NCCAM research education grants provide
      essential training for future clinicians and clinician-researchers. Building this
      workforce will facilitate multidisciplinary collaborations that address the
      unique needs for research that informs integrative clinical practice.

PMID- 25380145
TI  - Finger pointing to JC virus: a tale of two indexes.

PMID- 25380147
TI  - Tobacco smoking strengthens the association of elevated blood pressure with
      arterial stiffness: the Bogalusa Heart Study.
AB  - OBJECTIVES: The study assessed the hypothesis that smoking strengthens the
      association of adult arterial stiffness with long-term cumulative burden of blood
      pressure (BP) from childhood to adulthood. BACKGROUNDS: Tobacco smoking and
      elevated BPs are important risk factors of vascular stiffness. However, the
      synergistic effect of these two risk factors is not well established, especially
      for the long-term burden of elevated BP since childhood. METHODS: The study
      cohort consisted of 945 adults (661 whites and 284 blacks, aged 24-43 years) who
      have BP measured 4-15 times since childhood (aged 4-17 years) in Bogalusa,
      Louisiana. The adult arterial stiffness was measured as aorta-femoral pulse wave
      velocity (afPWV); the total area under the curve (AUC) and incremental AUC were
      used as a measure of long-term burden and trends of BP, respectively. RESULTS:
      Increased adult afPWV was significantly associated with higher adulthood (P <
      0.001), total AUC (P < 0.001) and incremental AUC (P < 0.001) values of SBP and
      DBP, but not with childhood BP, after adjusting for age, race, sex, BMI and heart
      rate. Furthermore, smoking was a significant predictor of increased adult afPWV
      and BP levels. In the interaction analyses, the increasing trend of afPWV with
      increasing adult SBP (P = 0.009) and its incremental AUC (P = 0.007) were
      significantly greater among the current smokers than among the nonsmokers. DBP
      showed a similar pattern regarding the smoking-BP interaction on afPWV.
      CONCLUSION: These results, by showing the synergistic effect of tobacco smoking
      and long-term BP measures from childhood to adulthood on arterial stiffening
      process, underscore the importance of undertaking preventive strategies early in
      life and smoking behavior control.

PMID- 25380148
TI  - Comparisons of auscultatory hybrid and automated sphygmomanometers with mercury
      sphygmomanometry in hypertensive and normotensive pregnant women: parallel
      validation studies.
AB  - OBJECTIVE: To find a suitable replacement for mercury sphygmomanometry to measure
      blood pressure (BP) accurately in normal and hypertensive pregnancy. METHODS: Two
      parallel validation studies were carried out in 340 pregnant women, 170 with a
      hypertensive disorder and 170 normotensive women. An auscultatory hybrid
      sphygmomanometer, A&D UM-101, and a professional automated oscillometric device
      for office and clinic use, Omron HEM-907, were tested. Using a modified British
      Hypertension Society (BHS) Protocol, nine sequential BP recordings were taken
      alternating between the mercury sphygmomanometer and the study device. The first
      readings for each device were discarded, and three differences between mercury
      and study device were calculated for each woman for SBP and DBP. Main outcome
      measures were the percentages of BP readings that were within 5, 10 and 15 mmHg
      absolute difference from mercury sphygmomanometry. RESULTS: Women in both studies
      were an average of 34 weeks' gestation and of similar ethnicity, age and BMI. In
      hypertensive women, 29% had preeclampsia and 73% were receiving
      antihypertensives. Amongst hypertensive women, SBP was within 5 mmHg of mercury
      BP in 94% of readings with the auscultatory device and 75% with the automated
      device (P = 0.021); DBP was within 5 mmHg in 97 and 61% readings, respectively (P
      = 0.001). Results were similar amongst normotensive pregnant women. Both devices
      achieved an A/A rating according to the BHS protocol. CONCLUSION: The
      auscultatory hybrid sphygmomanometer is more accurate than the automated
      oscillometric device in pregnancy, specifically in hypertensive pregnancies. It
      is an acceptable replacement for mercury sphygmomanometry in pregnancy.

PMID- 25380149
TI  - Comparison of single-pill strategies first line in hypertension:
      perindopril/amlodipine versus valsartan/amlodipine.
AB  - OBJECTIVES: An international double-blind, parallel-group, randomized controlled
      trial was performed to determine the efficacy and safety of a new first-line
      strategy in mild to moderate hypertension based on a single-pill combination of
      perindopril/amlodipine versus a validated stepped-care strategy (initiation with
      valsartan monotherapy, up-titrating to valsartan/amlodipine after 2 months).
      METHODS: At inclusion, patients received perindopril/amlodipine 3.5/2.5 mg or
      valsartan 80 mg. At 1, 2, and 3 months, patients were up-titrated if they had
      uncontrolled hypertension (>=140/90 mmHg). The up-titration steps were:
      perindopril/amlodipine 7/5 mg, 14/10 mg, and 14/10 mg + indapamide sustained
      release 1.5 mg; or valsartan 160 mg, valsartan/amlodipine 160/5 mg, and 160/10
      mg. The two groups were similar at baseline (55.5 years, 53% men, blood pressure
      163.5/100.2 mmHg); 881 perindopril/amlodipine and 876 valsartan/amlodipine
      patients were analyzed for efficacy. RESULTS: After 1 month, the rate of
      controlled hypertension was 33% with perindopril/amlodipine versus 27% with
      valsartan/amlodipine (estimate of difference, +6.1%; P = 0.005); this between
      strategy difference remained significant at every visit (P < 0.05). After 3
      months, blood pressure was 137.8 +/- 12.4/83.3 +/- 8.7 and 139.7 +/- 13.3/84.8 +/
      9.0 mmHg, respectively, with greater reductions from baseline with
      perindopril/amlodipine (primary endpoint -2.0/-1.5 mmHg; both P < 0.001). Similar
      results were observed at all other visits (all P <= 0.001). The safety of the two
      strategies was equivalent. CONCLUSIONS: The three-step strategy of initiation
      with single-pill perindopril/amlodipine produces greater reductions in blood
      pressure, and better and quicker rates of control of hypertension. This can be
      expected to be associated with benefits beyond blood pressure control, notably
      improved compliance and better cardioprotection.

PMID- 25380150
TI  - Pressure-dependence of arterial stiffness: potential clinical implications.
AB  - BACKGROUND: Arterial stiffness measures such as pulse wave velocity (PWV) have a
      known dependence on actual blood pressure, requiring consideration in
      cardiovascular risk assessment and management. Given the impact of ageing on
      arterial wall structure, the pressure-dependence of PWV may vary with age.
      METHODS: Using a noninvasive model-based approach, combining carotid artery echo
      tracking and tonometry waveforms, we obtained pressure-area curves in 23
      hypertensive patients at baseline and after 3 months of antihypertensive
      treatment. We predicted the follow-up PWV decrease using modelled baseline curves
      and follow-up pressures. In addition, on the basis of these curves, we estimated
      PWV values for two age groups (mean ages 41 and 64 years) at predefined
      hypertensive (160/90 mmHg) and normotensive (120/80 mmHg) pressure ranges.
      RESULTS: Follow-up measurements showed a near 1 m/s decrease in carotid PWV when
      compared with baseline, which fully agreed with our model-prediction given the
      roughly 10 mmHg decrease in diastolic pressure. The stiffness-blood pressure-age
      pattern was in close agreement with corresponding data from the 'Reference Values
      for Arterial Stiffness' study, linking the physical and empirical bases of our
      findings. CONCLUSION: Our study demonstrates that the innate pressure-dependence
      of arterial stiffness may have implications for the clinical use of arterial
      stiffness measurements, both in risk assessment and in treatment monitoring of
      individual patients. We propose a number of clinically feasible approaches to
      account for the blood pressure effect on PWV measurements.

PMID- 25380151
TI  - Identification of a common molecular pathway in hypertensive renal damage:
      comparison of rat and human gene expression profiles.
AB  - BACKGROUND: There is a common structural progression in hypertensive renal damage
      with early arterial damage and fibrosis in the juxtamedullary cortex. METHOD: The
      present investigation identifies a common pathway using three-gene expression
      profiles from hypertensive rat models: 60-week-old spontaneously hypertensive rat
      (SHR), salt-loaded stroke-prone SHR (SHRSP), and the non-clipped kidney after 24
      weeks of two-kidney, one-clip hypertension (2K1C). Kidney damage was scored using
      a specialized system. Gene-expression profiles were determined using microarrays
      and validated using a panel of 47 genes by quantitative real-time PCR. RESULTS:
      All groups showed kidney damage (SHRs: 0.32 +/- 0.09 vs. Wistar-Kyoto rats: 0.06
      +/- 0.03; 2K1C: 0.27 +/- 0.13 vs. pooled controls: 0.01 +/- 0.01; SHRSP: 1.13 +/-
      0.14 vs. WKY: 0.04 +/- 0.03; all P < 0.05). A total of 1614 genes were changed in
      the SHR experiment, 1323 in the SHRSP, and 576 in the 2K1C. Eighty-eight genes
      were similarly regulated in all three models. Gene ontology enrichment analysis
      identified 59 ontologies that were enriched in all three datasets. These included
      over-representation to extracellular matrix, response to oxidative stress, and
      immune system processes. Out of the 88 in-common genes, 40 could be connected in
      a common pathway that was compared to two gene-expression profiles from human
      kidneys with histologically verified fibrosis to identify a highly significant
      number of in-common genes that were also represented in the common genetic
      pathway. CONCLUSION: There is a common pathway during the development of
      hypertensive kidney damage in rats irrespective of model. Interestingly, large
      parts of this common pathway are conserved in human kidney damage, which may
      indicate a broader importance in the development of chronic kidney disease.

PMID- 25380152
TI  - Cocoa consumption dose-dependently improves flow-mediated dilation and arterial
      stiffness decreasing blood pressure in healthy individuals.
AB  - BACKGROUND: Cocoa flavonoids exert beneficial vascular effects and reduce the
      risk of cardiovascular morbidity and mortality. Nevertheless, the involved
      mechanisms have not been clarified and no study has yet focused on the dose
      response effects. OBJECTIVES: We aimed to investigate the effects of different
      doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1),
      pulse wave velocity (PWV), and SBP and DBP. DESIGN: According to a randomized,
      double-blind, controlled, cross-over design, 20 healthy volunteers (1.5%
      improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to
      receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500
      and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. RESULTS:
      Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and
      8.2% after the different flavonoid doses, respectively (P < 0.0001). Compared
      with the control, even 80  mg cocoa flavonoids per day increased FMD (P <
      0.0001). Cocoa dose-dependently decreased PWV (P < 0.0001). Cocoa intake
      decreased office blood pressure (BP) (SBP: -4.8 +/- 1.03  mmHg, P < 0.0001; DBP: 
      3.03 +/- 1.07 mmHg, P = 0.0011). With respect to control, cocoa ingestion
      decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064),
      daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with
      the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to
      15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses,
      respectively (P for treatment <0.05)]. Compared with the control, significant
      changes were observed for all doses of flavonoids (ET-1; P < 0.05). CONCLUSION:
      Our study showed for the first time that cocoa dose-dependently improved FMD and
      decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings
      are clinically relevant, suggesting cocoa, with very low calorie intake, might be
      reasonably incorporated into a dietary approach, representing a consistent tool
      in cardiovascular prevention.

PMID- 25380153
TI  - Motivating patients to exercise: translating high blood pressure into equivalent
      risk of inactivity.
AB  - OBJECTIVE: Even with the 2008 physical activity guidelines for Americans and the
      strong epidemiological evidence, physicians are not routinely emphasizing the
      importance of exercise. We try to explore an innovative way to communicate the
      benefits of physical activity in a term familiar to patients. METHODS AND
      RESULTS: A cohort of 470, 163 adults from a medical screening program in Taiwan
      were recruited between 1994 and 2008. Their vital status was followed up by
      matching with the National Death File. Individuals were classified as 'inactive',
      'low active', or 'fully active', with 'fully active' meeting the current exercise
      recommendation of 150  min per week or more. Cox proportional model was used to
      calculate the hazard ratio. More than one-half of the cohort was inactive (54%),
      with one-quarter fully active (24%). One in seven was hypertensive (14%), defined
      as SBP at least 140  mmHg. Among the hypertensive individuals, mortality risks
      were increased by 37% for the inactive. Inactive individuals had higher all-cause
      mortality than active ones across all blood pressure (BP) levels. At 110-119 
      mmHg, the inactive had a risk as high as the risk at 155  mmHg, an increased
      mortality risk equivalent to a risk of BP increase of 41.2 mmHg. CONCLUSION: The
      mortality risk of being inactive was equivalent to an increase of around 40  mmHg
      in SBP or 20  mmHg in DBP, a number relevant to hypertensive patients.
      Appreciating this relationship may convince the inactive to start exercising, a
      behavior as important as controlling BP.

PMID- 25380154
TI  - An estimate of the prevalence of hypertension in Nigeria: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Hypertension is a leading cause of morbidity and mortality in Africa,
      and Nigeria, the most populous country in the continent, hugely contributes to
      this burden. OBJECTIVE: To provide an improved estimate of the prevalence and
      number of cases of hypertension in Nigeria based on the cut-off 'at least 140/90 
      mmHg', towards ensuring better awareness, control and policy response in the
      country. METHODS: We conducted a systematic search of Medline, EMBASE and Global
      Health from January 1980 to December 2013 for population-based studies providing
      estimates on the prevalence of hypertension in Nigeria. From the extracted crude
      prevalence rates, we conducted a random-effects meta-analysis, and further
      estimated the overall awareness rate of hypertension in Nigeria, expressed as
      percentage of all hypertension cases. We applied a meta-regression
      epidemiological modelling, using United Nations population demographics for the
      years 2010 and 2030, to determine the prevalence and number of cases of
      hypertension in Nigeria for the 2 years. RESULTS: Our search returned 2260
      publications, 27 of which met our selection criteria. From the random-effects
      meta-analysis, we estimated an overall hypertension prevalence of 28.9% (25.1,
      32.8), with a prevalence of 29.5% (24.8, 34.3) among men and 25.0% (20.2, 29.7)
      among women. We estimated a prevalence of 30.6% (24.5, 36.6) and 26.4% (19.4,
      33.4) among urban and rural dwellers, respectively. The pooled awareness rate of
      hypertension was 17.4% (11.4, 23.3). The overall mean SBP was 128.6 (125.5,
      130.8) mmHg, and the DBP was 80.6 (78.5, 82.7) mmHg. From our modelling, we
      estimated about 20.8 million cases of hypertension in Nigeria among people aged
      at least 20 years in 2010, with a prevalence of 28.0% (24.6, 31.9) in both sexes 
      30.7% (24.9, 33.7) among men and 25.2% (22.7, 31.9) among women. By 2030, we
      projected an increase to 39.1 million cases of hypertension among people aged at
      least 20 years with a prevalence of 30.8% (24.5, 33.7) in both sexes - 32.6%
      (27.3, 38.2) among men and 29.0% (21.9-32.2) among women. CONCLUSIONS: Our
      findings suggest the prevalence of hypertension is high in Nigeria, and the
      overall awareness of raised blood pressure among hypertension cases is low in the
      country. We hope this study will inform appropriate public health response
      towards reducing this burden.

PMID- 25380155
TI  - Central blood pressure relates more strongly to retinal arteriolar narrowing than
      brachial blood pressure: the Nagahama Study.
AB  - OBJECTIVES: Although central blood pressure (BP) is considered to be more closely
      associated with large arterial remodeling and cardiovascular outcomes than
      brachial BP, few studies have investigated these associations with changes in
      small arteries. As morphological changes in retinal vessels might be associated
      with cardiovascular outcomes, we conducted a cross-sectional study to investigate
      the association of central BP with retinal vessel caliber. METHODS: The study
      included 8054 Japanese participants. Central BP was estimated by the radial
      arterial waveform by calibrating brachial BP. Central retinal arteriolar
      equivalent (CRAE) was computationally measured using fundus photography. RESULTS:
      CRAE was most strongly associated with central SBP (r = -0.324, P < 0.001),
      followed by DBP (r = -0.292, P < 0.001) and central pulse pressure (PP; r = 
      0.226, P < 0.001). The correlation coefficient between SBP and CRAE was
      significantly greater in central SBP than in brachial SBP (r = -0.300, P <
      0.001). After adjustment for possible covariates, brachial SBP (beta = -0.221, P
      < 0.001) and central SBP (beta = -0.239, P < 0.001) were independently associated
      with CRAE. Further, higher brachial SBP (beta = -0.226, P < 0.001) and smaller PP
      amplification (beta = 0.092, P < 0.001) were identified as independent
      determinants of narrowing of CRAE in the same equation, which indicated the
      superiority of central BP. Central BP-determined hypertensive individuals had a
      significantly narrower CRAE independent of brachial BP (central/brachial:
      hypertension/hypertension 121.4 +/- 11.5, hypertension/normotension 120.9 +/-
      11.2, normotension/hypertension 125.1 +/- 11.9, normotension/normotension 128.1
      +/- 11.5 MUm). CONCLUSION: Central BP was more closely associated with the
      narrowing of CRAE than brachial BP. Slight increases in central BP might be
      involved in the morphological changes in small retinal arteries, even in
      individuals with optimal brachial BP.

PMID- 25380156
TI  - c-Src, ERK1/2 and Rho kinase mediate hydrogen peroxide-induced vascular
      contraction in hypertension: role of TXA2, NAD(P)H oxidase and mitochondria.
AB  - AIM: : The aim of this study was to analyse the signalling pathways involved in
      H2O2 vascular responses in hypertension. METHODS: Vascular function, thromboxane
      A2 (TXA2) production, oxidative stress and protein expression were determined in
      mesenteric resistance arteries (MRAs) from hypertensive (spontaneously
      hypertensive rats, SHR) and normotensive Wistar Kyoto (WKY) rats. RESULTS: H2O2
      and the TP agonist U46619 induced greater contractile responses in MRA from SHR
      than WKY. Moreover, H2O2 increased TXA2 production more in SHR than in WKY. The c
      Src inhibitor PP1 reduced H2O2 and U46619-induced contraction and TXA2 release in
      both strains. The ERK1/2 inhibitor PD98059 reduced H2O2 but not U46619-induced
      contraction only in SHR arteries. The Rho kinase inhibitor Y26372 reduced H2O2
      and U46619-induced contractions only in SHR arteries. Basal c-Src, ERK1/2 and Rho
      kinase expression were greater in MRA from SHR than WKY. In SHR, the combination
      of PD98059 with the TP antagonist SQ29548 but not with Y27632 inhibited the H2O2
      contraction more than each inhibitor alone. H2O2 and U46619 increased NAD(P)H
      oxidase activity and O2 production and decreased mitochondrial membrane potential
      in vessels from SHR. The effects induced by H2O2 were abolished by inhibitors of
      TXA2 synthase, ERK1/2 and c-Src. The mitochondrial antioxidant mitoTEMPO reduced
      H2O2-induced contraction and NAD(P)H oxidase activation. CONCLUSION: In arteries
      from WKY, c-Src mediates H2O2 contractile responses by modulating TXA2 release
      and TXA2 effect. In SHR, H2O2 induces c-Src dependent TXA2 release that provokes
      vascular contractile responses through Rho kinase, c-Src and O2 from NAD(P)H
      Oxidase and mitochondria. Moreover, ERK1/2 activation contributes to H2O2
      contraction in SHR through effects on mitochondria/NAD(P)H Oxidase.

PMID- 25380157
TI  - Influence of obesity in central blood pressure.
AB  - BACKGROUND: Obesity is an important risk factor for cardiovascular disease and
      has become a major concern in healthcare due to its high prevalence worldwide.
      The aim of the present study was to investigate the impact of BMI on central
      blood pressure (BP) and pulse wave velocity (PWV) in normotensive and
      hypertensive patients. PATIENTS AND METHODS: Normotensive and hypertensive adult
      patients who attended the outpatient clinic of cardiovascular risk were included.
      Peripheral BP was obtained in the brachial artery by using an oscillometric
      device (OMRON M-6). Central aortic BP waveform was reconstructed from the radial
      artery pressure waveforms (SphygmoCor, AtCor Medical, Sydney, Australia) and
      central BP was calculated. Carotid-femoral PWV was measured by an automatic
      device (Complior, Artech, France). RESULTS: We examined a total of 351 patients
      [50.7% women; 77 patients normal-weight (BMI < 25 kg/m)], 274 patients overweight
      or obese (BMI >=25 kg/m). Central SBP showed a positive association with male sex
      and mean BP, but a negative association with overweight/obesity. PWV was
      positively associated with age, male sex, central BP, peripheral BP and BP
      treatment, whereas BMI of at least 25 kg/m led to a decrease in PWV in patients
      with the same central SBP levels. Likewise, PWV was lower in the overweight/obese
      group compared to the normal-weight group at the same central SBP. CONCLUSION:
      Overweight and obesity tend to have lower central SBP as compared to lean
      patients, mainly in women. Further research is required to assess the interaction
      between body weight and vascular dynamics and their clinical implications.

PMID- 25380158
TI  - Lectin-like oxidized low-density lipoprotein receptor-1 regulates autophagy and
      Toll-like receptor 4 in the brain of hypertensive mice.
AB  - BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)
      regulates blood pressure and is important for the development of inflammation,
      oxidative stress and autophagy. We posited that LOX-1 via NADPH oxidase
      activation may affect autophagy and Toll-like receptor (TLR)4 expression in the
      brains of hypertensive mice. METHODS: To examine this postulate, wild-type mice
      were given continuous infusion of angiotensin II (50 ng/min) for 28 days. As
      expected, these mice developed significant increase in blood pressure. RESULTS:
      Corpus callosum in the brains of these hypertensive mice revealed intense
      expression of NADPH oxidase (subunits P22phox and P47phox), activation of P38
      MAPK and nuclear factor-kappaB (P65), autophagy-related proteins (beclin-1 and
      conversion of LC3-I to LC3-II), and TLR4 (and associated signaling molecules
      myeloid differentiation primary response gene (88) and TIR-domain-containing
      adapter-inducing interferon-beta). These observations suggested activation of
      redox signals, autophagy and immune system. In parallel experiments, mice with
      LOX-1 deletion given similar infusion of angiotensin II showed much less
      expression of NADPH oxidase, activation of P38 MAPK and nuclear factor-kappaB,
      autophagy-related proteins and TLR4 [and myeloid differentiation primary response
      gene (88) and TIR-domain-containing adapter-inducing interferon-beta]. Mice with
      LOX-1 deletion also showed a smaller rise in blood pressure than wild-type mice,
      both groups given similar infusion of angiotensin II. CONCLUSION: These studies
      suggest immune activation in the brains of mice with angiotensin II-induced
      hypertension. Further, these observations imply the existence of a link between
      LOX-1, NADPH oxidase expression, development of autophagy and immune activation
      in hypertension.

PMID- 25380159
TI  - Acute effects of noise exposure on 24-h ambulatory blood pressure in hypertensive
      adults.
AB  - OBJECTIVE: Noise exposure is associated with elevated blood pressure, but the
      effects on susceptible workers have not been reported. This repeated-measure
      study investigated the effects of noise exposure on 24-h ambulatory blood
      pressure among hypertensive, pre-hypertensive, and normotensive adults. METHODS:
      We enrolled 113 volunteers in an occupational cohort in 2009. Individual noise
      exposure and personal blood pressure were measured simultaneously over 24 h on
      working and non-working days. Linear mixed-effects regressions were used to
      estimate the effects on SBP and DBP by controlling for potential confounders.
      RESULTS: Each A-weighted decibel (dBA) increase in a 30-min time-lagged exposure
      was associated with transient elevations of work-time SBP [0.30 (95% confidence
      interval: 0.06, 0.54) mmHg] on working days as well as sleep-time SBP [0.39
      (0.12, 0.66) mmHg] and DBP [0.33 (0.14, 0.51) mmHg] on non-working days among 19
      hypertensive adults. In contrast, 46 normotensive workers had transient increases
      in work-time SBP [0.16 (0.03, 0.29) mmHg] and DBP [0.25 (0.15, 0.34) mmHg] on
      working days as well as sleep-time SBP [0.17 (0.06, 0.29) mmHg] and DBP [0.21
      (0.14, 0.29) mmHg] on non-working days caused by a 1-dBA increase in the current
      exposure. All groups had sustained increases in 24-h average ambulatory SBP and
      DBP induced by noise exposure on 2 days, but the hypertensive workers had the
      most pronounced increase in SBP. CONCLUSION: Hypertensive adults are more
      susceptible to noise exposure with a greater effect on ambulatory SBP. These
      results suggest a need for more protection for this subpopulation.

PMID- 25380160
TI  - Efficacy of the superoxide dismutase mimetic tempol in animal hypertension
      models: a meta-analysis.
AB  - OBJECTIVE: Considering the growing body of evidence that indicates the
      contribution of superoxide anions (O2) and other reactive oxygen species (ROS) to
      the development of hypertension, we assessed whether animal models of
      hypertension have a benefic effect with tempol, a superoxide dismutase mimetic,
      to help augment the design of future studies. METHODS: Studies published between
      July 1998 and December 2012 on blood pressure (BP) in different hypertensive
      models were obtained after an electronic and manual search of PubMed. In-depth
      analyses of the methodological quality of the studies and the mean arterial
      pressure (MAP) changes after treatment with tempol were performed, as well as the
      subgroup analyses on the route of tempol delivery. RESULTS: Out of the 144
      identified studies, 28 were included after screening. The data showed that tempol
      reduced MAP by computing the standardized mean difference with the value of 4.622
      (95% confidence interval 3.24-5.99). The quality of studies included in the meta
      analysis was category II; however, omission of details in the trials might have
      biased the results. There was substantial heterogeneity in the results with an I
      of 94.45%, which persisted after stratifying for the route of tempol delivery.
      CONCLUSION: In conclusion, this analysis shows that antioxidant treatment with
      tempol can reduce BP, suggesting that ROS plays a role in the pathogenesis of
      increased BP in the hypertension models used in the current research practice.

PMID- 25380161
TI  - Genetics of systolic and diastolic heart failure.
AB  - Heart failure accounts for a significant portion of heart diseases. Molecular
      mechanisms gradually emerge that participate in pathways leading to left
      ventricular dysfunction in common systolic heart failure (SHF) and diastolic
      heart failure (DHF). A human genome-wide association study (GWAS) identified two
      markers for SHF and no GWAS on DHF has been documented. However, genetic analyses
      in rat models of SHF and DHF have begun to unravel the genetic components known
      as quantitative trait loci (QTLs) initiating systolic and diastolic function. A
      QTL for systolic function was detected and the gene responsible for it is
      identified to be that encoding the soluble epoxide hydrolase. Diastolic function
      is determined by multiple QTLs and the Ccl2/monocyte chemotactic protein gene is
      the strongest candidate. An amelioration on diastolic dysfunction is merely
      transient from changing such a single QTL accompanied by a blood pressure
      reduction. A long-term protection can be achieved only via combining alleles of
      several QTLs. Thus, distinct genes in synergy are involved in physiological
      mechanisms durably ameliorating or reversing diastolic dysfunction. These data
      lay the foundation for identifying causal genes responsible for individual
      diastolic function QTLs and the essential combination of them to attain a
      permanent protection against diastolic dysfunction, and consequently will
      facilitate the elucidation of pathophysiological mechanisms underlying
      hypertensive diastolic dysfunction. Novel pathways triggering systolic and
      diastolic dysfunction have emerged that will likely provide new diagnostic tools,
      innovative therapeutic targets and strategies in reducing, curing and even
      reversing SHF and DHF. 

PMID- 25380162
TI  - White-coat hypertension, as defined by ambulatory blood pressure monitoring, and
      subclinical cardiac organ damage: a meta-analysis.
AB  - AIM: : The clinical and prognostic relevance of white-coat hypertension (WCH) has
      not been fully elucidated; in particular, the association of this blood pressure
      phenotype with suclinical organ damage remains unclear. We performed a systematic
      meta-analysis in order to provide a comprehensive information on cardiac
      structural and functional changes in WCH, as defined by ambulatory blood pressure
      monitoring. DESIGN: Studies were identified by the following search terms: 'white
      coat hypertension', 'isolated clinic hypertension', 'cardiac organ damage',
      'target organ damage', 'left ventricle', 'left ventricular hypertrophy', 'cardiac
      hypertrophy', 'ventricular dysfunction', and 'echocardiography'. RESULTS: A total
      of 7382 untreated adult patients (2493 normotensive, 1705 WCH, and 3184
      hypertensive individuals) included in 25 studies were considered. Left
      ventricular mass index was higher in WCH than in normotensive patients
      [standardized difference in mean (SDM) 0.50, P < 0.01]; mitral E/A ratio was
      lower (SDM -0.27, P < 0.01) and left atrium larger (SDM 0.29, P < 0.05) in WCH
      than in the normotensive counterparts. Hypertensive patients showed a greater
      left ventricular mass index (SDM 0.42, P < 0.01), reduced E/A (SDM -0.15, P <
      0.01), and larger left atrium diameter (SDM 0.27, P < 0.01) than WCH patients.
      CONCLUSIONS: Our meta-analysis shows that alterations in cardiac structure and
      function in WCH patients, as defined by ambulatory blood pressure monitoring, are
      intermediate between sustained hypertensive patients and normotensive controls.
      The study supports the view that WCH should not be further considered a fully
      benign entity.

PMID- 25380163
TI  - Feasibility and quality of cardiovascular disease prevention within a community
      based health insurance program in rural Nigeria: an operational cohort study.
AB  - OBJECTIVE: To assess the feasibility of providing guideline-based cardiovascular
      disease (CVD) prevention care within the context of a community-based health
      insurance program (CBHI) in rural Nigeria. METHODS: A prospective operational
      cohort study was conducted in a primary healthcare clinic in rural Nigeria,
      participating in a CBHI program. The insurance program provided access to care
      and improved the quality of the clinics participating in the program, including
      CVD prevention guideline implementation. Insured adults at risk of CVD were
      consecutively included upon clinic attendance. The primary outcome was quality of
      care determined by scoring of quality indicators on patient files of the cohort,
      1.5 year after guideline implementation. RESULTS: Of the 368 screened patients,
      349 were included and 323 (93%) completed 1 year of follow-up. The majority of
      patients (331, 95%) had hypertension. Process indicators showed that 114/115
      (99%) new hypertension cases had a record of CVD risk assessment and 249/333
      (75%) eligible cases a record of lifestyle advice. Outcome indicators showed that
      in 292/328 (64%) hypertension cases, blood pressure was on target. Barriers to
      care included limited human resources, limited affordability of diagnostic tests
      and multidrug regimes for the healthcare provider, frequent doctor's
      appointments, and inefficient drug supplies. CONCLUSION: Implementation of CVD
      prevention care within the context of a CBHI program resulted in high-quality
      care in rural sub-Saharan Africa, comparable to high-income countries. However,
      guideline implementation was resource-intense and specific recommendations were
      not feasible. Simple models of care delivery are needed for rapid scale-up of CVD
      prevention services in sub-Saharan Africa.

PMID- 25380165
TI  - Portable indices for sarcopenia are associated with pressure wave reflection and
      central pulse pressure: the J-SHIPP study.
AB  - OBJECTIVE: We recently reported that thigh muscle sarcopenia measured by computed
      tomography is related to arterial stiffness, pressure wave reflection, and
      central pulse pressure (PP). However, it remains to be determined whether more
      straightforward and simple techniques such as hand grip strength and the bio
      impedance method are also useful for the clinical evaluation of sarcopenia.
      METHODS: A total of 1593 middle-aged to older patients participated in this cross
      sectional study. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an
      index of arterial stiffness. Second PP (PP2) at the second peak of radial SBP was
      used to estimate central PP. Radial augmentation index was calculated as PP2/PP.
      Thigh muscle cross-sectional area and abdominal visceral fat area were quantified
      by computed tomography. Patients were classified as sarcopenic if their hand grip
      strength or skeletal muscle mass (measured by bioelectrical impedance) was more
      than 1 SD lower than the mean of those in a reference group aged below 50 years,
      or in the lowest 20% of the studied population. Visceral obesity was defined as
      visceral fat area greater than 100 cm. RESULTS: Antidyslipidemia drug and
      antidiabetic drug were significantly associated with lower hand grip strength.
      Both sarcopenic indices were significantly and independently associated with
      baPWV, radial augmentation index, and PP2. Sarcopenia defined by either criterion
      was significantly associated with higher baPWV, radial augmentation index, and
      PP2. Visceral obesity was significantly associated only with baPWV. CONCLUSION:
      These findings indicate the clinical usefulness of noninvasive methods for
      assessment of sarcopenia, which is a risk factor for cardiovascular disease.

PMID- 25380164
TI  - Costs of cardiovascular disease prevention care and scenarios for cost saving: a
      micro-costing study from rural Nigeria.
AB  - OBJECTIVE: To assess the costs of cardiovascular disease (CVD) prevention care
      according to international guidelines, in a primary healthcare clinic in rural
      Nigeria, participating in a health insurance programme. METHODS: A micro-costing
      study was conducted from a healthcare provider perspective. Activities per
      patient per year (e.g., consultations, diagnostic tests) were based on clinical
      practice in the study clinic. Direct (e.g., staff, drugs) and indirect cost items
      (overheads) for each activity were measured. A cohort study, patient and staff
      observations, and interviews in the study clinic provided patient resource
      utilization data. Univariate sensitivity analyses were performed. Scenario
      analyses evaluated cost-saving options. The main outcome was the costs of CVD
      prevention care per patient per year. RESULTS: The costs of CVD prevention care
      were United States dollars (USD) 144 (range 130-158) per patient per year. Direct
      costs were USD 82 and indirect costs were USD 62. The main cost drivers were
      drugs (USD 39) and diagnostic tests (USD 36). The costs of hypertension care were
      USD 118 (107-132) and that of diabetes care USD 263 (236-289) per patient per
      year. A combination of task-shifting from doctors to nurses, reduction of
      appointment frequencies, and minimal organ damage screening would result in a
      direct cost reduction of 42%. CONCLUSION: This is the first study to report the
      costs of CVD prevention care in sub-Saharan Africa, based on prospectively
      collected operational data. The costs observed in our study are unaffordable in
      many countries in sub-Saharan Africa, highlighting the need for innovative
      financing mechanisms to fund CVD prevention care.

PMID- 25380166
TI  - Prevalence and control of hypertension in Bangladesh: a multilevel analysis of a
      nationwide population-based survey.
AB  - OBJECTIVES: We investigated the prevalence, awareness, treatment, and control of
      hypertension and associated risk factors in the Bangladeshi adult population.
      METHODS: The data for this study were extracted from the nationally
      representative 2011 Bangladesh Demographic and Health Survey. Socio-demographic
      profiles, height, weight, blood pressure measurements, and management were
      recorded from 7876 adults aged 35 years or older. Multilevel logistic regression
      models were used to identify the risk factors for hypertension awareness,
      treatment, and control. RESULTS: Overall, age-standardized prevalence of
      prehypertension and hypertension were 27.1 and 24.4%, respectively. Among
      patients with hypertension, 50.1% were aware of their condition, 41.2% were in
      treatment, but only 31.4% had controlled hypertension. There was a wide disparity
      in hypertension management between the poor and the wealthy households. Rich
      households were more likely to be aware of their hypertension [odds ratio (OR)
      1.92, 95% confidence interval (CI) 0.97-3.79, P = 0.06], receiving treatment (OR
      3.34, 95% CI 1.55-7.18, P < 0.001) and controlling their condition (OR 2.88, 95%
      CI 1.28-6.46, P = 0.01), as compared to the poor residents. Participants who had
      lower education were less likely to be aware of, in treatment for, and in control
      of their condition. CONCLUSION: One in four adults had hypertension in
      Bangladesh, and awareness and treatment of hypertension are quite low.
      Improvements in detection and treatment strategies are needed to prevent the
      growing disease burden associated with hypertension.

PMID- 25380167
TI  - Effects of multielectrode renal denervation on cardiac and neurohumoral
      adaptations in resistant hypertension with cardiac hypertrophy: an EnligHTN I
      substudy.
AB  - OBJECTIVE: This EnligHTN I nonrandomized substudy investigated the effect of
      multielectrode renal denervation (RDN) on cardiac and neurohumoral adaptations.
      METHODS: Eighteen patients with true drug-resistant hypertension [age: 56 +/- 10
      years, 12 men, BMI: 33.6 +/- 5.4 kg/m, office blood pressure (BP) by automatic
      device (Omron): 182 +/- 19/97 +/- 18 mmHg and ambulatory BP (Spacelabs): 153 +/-
      16/87 +/- 15 mmHg receiving 4.5 antihypertensive drugs/day] and left ventricular
      hypertrophy underwent multielectrode RDN (EnligHTN system; St. Jude Medical),
      whereas 10 patients served as controls. Both groups were followed-up for 6
      months. RESULTS: Demographic data were homogenous between both patient groups. In
      addition to reduction of office (-42/-17 mmHg, P < 0.001) and ambulatory (-19/-9
      mmHg, P < 0.001) BP, RDN contributed to attenuation of left ventricular mass
      index from 140.0 +/- 17.0 g/m (57.9 +/- 7.9 g/m) to 126.7 +/- 19.2 g/m (52.6 +/-
      8.4 g/m) (P < 0.01 for both) and left atrial diameter from 42.4 +/- 4.3 to 40.6
      +/- 3.6 mm (P = 0.004) at 6 months. Up to 56% of the RDN-group patients achieved
      a target of less than 140/90 mmHg in the office BP; proportion of RDN-group
      patients with concentric left ventricular hypertrophy had decreased by 39%;
      mitral lateral E/E' ratio decreased from 14.8 +/- 6.1 to 12.0 +/- 3.2 (P =
      0.016); isovolumic relaxation time shortened from 109.8 +/- 16.2 to 100.8 +/-
      17.1 ms (P = 0.003); and N-terminal pro B-type natriuretic peptide levels reduced
      from 84.9 +/- 35.9 to 57.2 +/- 38.8 pg/ml (P < 0.001) significantly at 6 months
      post-RDN. Control patients exhibited no significant changes in all the above
      parameters (P > 0.05) at 6 months. CONCLUSION: Multielectrode RDN contributes to
      improvement of diastolic dysfunction, reduction of left ventricular mass and
      attenuation of NT-proBNP, suggesting additional cardiovascular benefits in drug
      resistant hypertension associated with left ventricular hypertrophy.

PMID- 25380168
TI  - Low blood pressure during the acute period of ischemic stroke is associated with
      decreased survival.
AB  - OBJECTIVES: There is no agreement on optimal blood pressure (BP) level during the
      acute phase of stroke, because studies on the relation between BP and stroke
      outcome have shown contradicting results. The aim of this study was to compare
      the relationship of admission, maximal, discharge BP and its components during
      hospitalization for the first-ever acute ischemic stroke with total mortality
      after stroke. METHODS: In 532 consecutive patients (mean age 66 +/- 10 years, 59%
      of men) hospitalized for their first-ever ischemic stroke, the association
      between BP and total mortality during a median follow-up of 66 weeks
      (interquartile range 33-119 weeks) was analyzed. RESULTS: In multivariate
      analysis, both admission mean BP (MBP) and discharge SBP quartiles were
      independent predictors of mortality and outperformed other parameters of BP.
      After multivariate adjustments, patients with admission MBP below 100 mmHg had a
      higher risk of death than those with MBP between 100-110 and 110-121 mmHg,
      whereas the risk of mortality did not differ from the group with admission MBP
      above 122 mmHg. Similarly, patients with discharge SBP below 120 mmHg had an
      increased risk of death as compared to groups with SBP between 120-130 and 130
      141 mmHg, whereas the risk of death was similar to that with discharge SBP above
      141 mmHg. CONCLUSION: Among patients hospitalized for their first-ever ischemic
      stroke, the risk of all-cause death is significantly increased in those with
      admission MBP below 100 mmHg and discharge SBP below 120 mmHg, even after
      adjustments for other confounders.

PMID- 25380169
TI  - Distinct neural patterns enable grasp types decoding in monkey dorsal premotor
      cortex.
AB  - OBJECTIVE: Recent studies have shown that dorsal premotor cortex (PMd), a
      cortical area in the dorsomedial grasp pathway, is involved in grasp movements.
      However, the neural ensemble firing property of PMd during grasp movements and
      the extent to which it can be used for grasp decoding are still unclear.
      APPROACH: To address these issues, we used multielectrode arrays to record both
      spike and local field potential (LFP) signals in PMd in macaque monkeys
      performing reaching and grasping of one of four differently shaped objects. MAIN
      RESULTS: Single and population neuronal activity showed distinct patterns during
      execution of different grip types. Cluster analysis of neural ensemble signals
      indicated that the grasp related patterns emerged soon (200-300 ms) after the go
      cue signal, and faded away during the hold period. The timing and duration of the
      patterns varied depending on the behaviors of individual monkey. Application of
      support vector machine model to stable activity patterns revealed classification
      accuracies of 94% and 89% for each of the two monkeys, indicating a robust,
      decodable grasp pattern encoded in the PMd. Grasp decoding using LFPs, especially
      the high-frequency bands, also produced high decoding accuracies. SIGNIFICANCE:
      This study is the first to specify the neuronal population encoding of grasp
      during the time course of grasp. We demonstrate high grasp decoding performance
      in PMd. These findings, combined with previous evidence for reach related
      modulation studies, suggest that PMd may play an important role in generation and
      maintenance of grasp action and may be a suitable locus for brain-machine
      interface applications.

PMID- 25380170
TI  - The correlation between red blood cell distribution width levels with the
      severity of obstructive sleep apnea and carotid intima media thickness.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is characterized by
      repetitive collapse of the upper airway during sleep. Red blood cell distribution
      width (RDW) increases platelet activation and has been reported as an independent
      predictor of adverse outcomes in the general population and is believed to be
      associated with cardiovascular morbidity and mortality. We evaluated RDW, mean
      platelet volume (MPV), and platelet distribution width (PDW) as a severity index
      in OSAS and the relationship between carotid intima media thickness and pulmonary
      hypertension. MATERIAL/METHODS: The study population consisted of 99 patients who
      were admitted to the sleep laboratory. Based on the apnea-hypopnea index,
      patients were grouped into 3 OSAS severity categories. Morning blood samples were
      withdrawn from patients after a 12-hour fasting period. MPV, PDW, and RDW were
      measured in a blood sample. Bilateral common carotid arteries of the patients
      were scanned. RESULTS: Ninety-nine patients--73 with OSAS and 26 simple snoring
      control cases--were included. Mean values of MPV, PDW, and RDW were similar in
      patients compared to simple snoring subjects in the control group (p=0.162,
      p=0.656, p=0.091). RDW showed an inverse correlation with mean desaturation and
      lowest desaturation (p<0.01). Body mass index, apnea-hypopnea index, pulmonary
      artery pressure, and desaturation time under 90% were positively correlated with
      RDW (p<0.05). MPV, PDW, and carotid intima media thickness had no correlation
      with any other parameters. CONCLUSIONS: The study showed a positive relationship
      between RDW and the apnea-hypopnea index and systolic pulmonary hypertension in
      patients with OSAS.

PMID- 25380172
TI  - Complications following preresection shunting in patients with posterior fossa
      tumors.

PMID- 25380171
TI  - Differential antigen expression profile predicts immunoreactive subset of
      advanced ovarian cancers.
AB  - The presence and composition of lymphocytes characterizing an immune response has
      been connected to prognosis in advanced ovarian cancer. Our aim is to establish
      novel associations between prognosis and the expression of immune-related genes
      through a focused screen utilizing publicly available high-throughput assays. We
      consider transcriptome profiles from n=1137 advanced ovarian cancer patients
      observed in four separate studies divided into discovery/validation sets
      (n=503/n=634). We focus on a subset of lymphocyte markers, antigen presentation
      and processing genes, T cell receptor associated co-stimulatory/repressor genes
      and cancer testis (CT) antigens. We modeled differential expression and co
      expression using these subsets and tested for association with overall survival.
      Fifteen of 64 immune-related genes are associated with survival of which 5 are
      reproduced in the validation set. The expression of these genes defines an
      immunoreactive (IR) subgroup of patients with a favorable prognosis. Phenotypic
      characterization of the immune compartment signal includes upregulation of
      markers of CD8+ T-cell activation in these patients. Using multivariate model
      building, we find that the expression of 6 CT antigens can predict IR status in
      the discovery and validation sets. These analyses confirm that a genomic approach
      can reproducibly detect lymphocyte signals in tumor tissue suggesting a novel way
      to study the tumor microenvironment. Our search has identified new candidate
      prognostic markers associated with immune components and uncovered preliminary
      evidence of prognostic subgroups associated with different immune mechanisms.

PMID- 25380173
TI  - Cerebral paragonimiasis: a retrospective analysis of 27 cases.
AB  - OBJECT: The authors retrospectively analyzed the clinical characteristics,
      existing problems, and treatment experiences in recently diagnosed cerebral
      paragonimiasis (CP) cases and sought to raise awareness of CP and to supply
      reference data for early diagnosis and treatment. METHODS: Twenty-seven patients
      (22 male and 5 female; median age 20.3 years, range 4-47 years) with CP were
      diagnosed between September 2008 and September 2013. These diagnoses were
      confirmed by IgG enzyme-linked immunosorbent assays. Follow-up was performed in
      24 cases for a period of 6-56 months. RESULTS: Cerebral paragonimiasis accounted
      for 21.6% of paragonimiasis cases (27 of 125). The average duration from onset to
      praziquantel treatment was 69 days. All patients resided in rural areas. Twenty
      patients had positive lung results, which included visible lung lesions in 14
      cases. The lesions were surgically removed in 8 of these cases. Twenty-four
      patients had high eosinophil counts (>= 0.08 * 10(9)/L), and eosinophilic
      meningitis was noted in 17 cases. The rate of misdiagnosis and missed diagnosis
      was 30.4%. Most symptoms were markedly improved after treatment, but mild
      movement disorders combined with impaired memory and personality changes remained
      in a small number of patients. CONCLUSIONS: Clinicians should be alert to the
      possibility of CP in young patients (4-16 years) with the primary symptoms of
      epilepsy and hemorrhage. Early diagnosis and timely treatment can reduce the need
      for surgery and further impairments to brain function. Liquid-based cytological
      examination of CSF and peripheral blood eosinophil counts can aid in
      differentiating CP from similar lesions.

PMID- 25380174
TI  - Hemispherectomy for treatment of refractory epilepsy in the pediatric age group:
      a systematic review.
AB  - OBJECT: Evidence in support of hemispherectomy stems from a multitude of
      retrospective studies illustrating individual institutions' experience. A
      systematic review of this topic, however, is lacking in the literature. METHODS:
      A systematic review of hemispherectomy for the treatment of refractory epilepsy
      available up to October 2013 was performed using the following inclusion
      criteria: reports of a total of 10 or more patients in the pediatric age group
      (<= 20 years) undergoing hemispherectomy, seizure outcome reported after a
      minimum follow-up of 1 year after the initial procedure, and description of the
      type of hemispherectomy. Only the most recent paper from institutions that
      published multiple papers with overlapping study periods was included. Two
      reviewers independently applied the inclusion criteria and extracted all the
      data. RESULTS: Twenty-nine studies with a total of 1161 patients met the
      inclusion criteria. Seizure outcome was available for 1102 patients, and the
      overall rate of seizure freedom at the last follow-up was 73.4%. Sixteen studies
      (55.2%) exclusively reported seizure outcomes of a single type of
      hemispherectomy. There was no statistically significant difference in seizure
      outcome and type of hemispherectomy (p = 0.737). Underlying etiology was reported
      for 85.4% of patients with documented seizure outcome, and the overall
      distribution of acquired, developmental, and progressive etiologies was 30.5%,
      40.7%, and 28.8%, respectively. Acquired and progressive etiologies were
      associated with significantly higher seizure-free rates than developmental
      etiologies (p < 0.001). Twenty of the 29 studies (69%) reported complications.
      The overall rate of hydrocephalus requiring CSF diversion was 14%. Mortality
      within 30 days was 2.2% and was not statistically different between types of
      hemispherectomy (p = 0.787). CONCLUSIONS: Hemispherectomy is highly effective for
      treating refractory epilepsy in the pediatric age group, particularly for
      acquired and progressive etiologies. While the type of hemispherectomy does not
      have any influence on seizure outcome, hemispherotomy procedures are associated
      with a more favorable complication profile.

PMID- 25380175
TI  - Thrombosis and spontaneous recanalization of a giant intracranial aneurysm:
      diagnostic and management pearls in a pediatric patient.
AB  - The authors present the case of a boy who was successfully managed through the
      spontaneous thrombosis of a cavernous internal carotid artery (ICA) aneurysm, the
      subsequent occlusion of the ICA, its recanalization, and ultimate endovascular
      sacrifice, using only two angiograms because of the diagnostic capability of CT
      angiography. Spontaneous recanalization of the ICA following occlusion in the
      setting of a giant aneurysm has not been previously reported. 

PMID- 25380176
TI  - Infratentorial complications following preresection CSF diversion in children
      with posterior fossa tumors.
AB  - OBJECT: This report presents the incidence, causes, and morbidity and mortality
      of infratentorial complications following CSF diversion before resection in
      children with posterior fossa tumors. METHODS: The medical records of 437
      children admitted to Abo El-Reesh Pediatric University Hospital with a diagnosis
      of posterior fossa tumor between 2005 and 2012 were retrospectively reviewed.
      Seven children developed neurological deterioration following CSF diversion due
      to infratentorial complications. Computed tomography scans revealed intratumoral
      hemorrhage (ITH) in 5 cases, while upward transtentorial herniation (UTH), as
      evidenced by obliteration of the quadrigeminal and ambient cisterns, was
      diagnosed in 2 cases. RESULTS: Hydrocephalus was noted in 381 patients, and 301
      patients underwent CSF diversion before resection. A ventriculoperitoneal (VP)
      shunt was used in 214 patients, and 6 children (2.8% of shunted cases)
      deteriorated neurologically (4 due to ITH and 2 due to UTH). Endoscopic third
      ventriculostomy (ETV) was performed in 87 patients, 1 of whom developed ITH (1.1%
      of the patients undergoing ETV). Six patients deteriorated within 8 hours
      (85.7%), whereas 1 patient, the only survivor, deteriorated after 24 hours. The
      incidence of infratentorial complications between VP shunts and ETVs was not
      found to be significantly different (p = 0.659). There was a higher risk of such
      complications in large posterior fossa tumors (diameter >= 4 cm) extending close
      to the tentorial incisura, especially in patients with severe hydrocephalus and
      significant peritumoral edema. CONCLUSIONS: Infratentorial complications (ITH and
      UTH) in children with posterior fossa tumors are not uncommon (2.3%) after
      preresection CSF diversion (VP shunt or ETV) and are associated with a very poor
      prognosis in most cases, even with surgical intervention.

PMID- 25380177
TI  - A search for radical intermediates in the photocycle of LOV domains.
AB  - LOV domains are the light sensitive parts of phototropins and many other light
      activated enzymes that regulate the response to blue light in plants and algae as
      well as some fungi and bacteria. Unlike all other biological photoreceptors known
      so far, the photocycle of LOV domains involves the excited triplet state of the
      chromophore. This chromophore is flavin mononucleotide (FMN) which forms a
      covalent adduct with a cysteine residue in the signaling state. Since the
      formation of this adduct from the triplet state involves breaking and forming of
      two bonds as well as a change from the triplet to the singlet spin state, various
      intermediates have been proposed, e.g. a protonated triplet state (3)FMNH(+), the
      radical anion (2)FMN(-), or the neutral semiquinone radical (2)FMNH. We performed
      an extensive search for these intermediates by two-dimensional transient
      absorption (2D-TA) with a streak camera. However, no transient with a rate
      constant between the decay of fluorescence and the decay of the triplet state
      could be detected. Analysis of the decay associated difference spectra results in
      quantum yields for the formation of the adduct from the triplet of PhiA(LOV1) ~
      0.75 and PhiA(LOV2) ~ 0.80. This is lower than the values PhiA(LOV1) ~ 0.95 and
      PhiA(LOV2) ~ 0.99 calculated from the rate constants, giving indirect evidence of
      an intermediate that reacts either to form the adduct or to decay back to the
      ground state. Since there is no measurable delay between the decay of the triplet
      and the formation of the adduct, we conclude that this intermediate reacts much
      faster than it is formed. The LOV1-C57S mutant shows a weak and slowly decaying
      (tau > 100 MUs) transient whose decay associated spectrum has bands at 375 and
      500 nm, with a shoulder at 400 nm. This transient is insensitive to the pH change
      in the range 6.5-10.0 but increases on addition of beta-mercaptoethanol as the
      reducing agent. We assign this intermediate to the radical anion which is
      protected from protonation by the protein. We propose that the adduct is formed
      via the same intermediate by combination of the radical ion pair. 

PMID- 25380178
TI  - A reverse gear for transcription-coupled DNA repair? (Comment on DOI
      10.1002/bies.201400106).

PMID- 25380179
TI  - Emotion beliefs and cognitive behavioural therapy for social anxiety disorder.
AB  - Despite strong support for the efficacy of cognitive behavioural therapy (CBT)
      for social anxiety disorder (SAD), little is known about mechanisms of change in
      treatment. Within the context of a randomized controlled trial of CBT, this study
      examined patients' beliefs about the fixed versus malleable nature of anxiety
      their 'implicit theories'-as a key variable in CBT for SAD. Compared to waitlist
      (n = 29; 58% female), CBT (n = 24; 52% female) led to significantly lower levels
      of fixed beliefs about anxiety (Mbaseline = 11.70 vs. MPost = 7.08, d = 1.27).
      These implicit beliefs indirectly explained CBT-related changes in social anxiety
      symptoms (kappa(2) = .28, [95% CI = 0.12, 0.46]). Implicit beliefs also uniquely
      predicted treatment outcomes when controlling for baseline social anxiety and
      other kinds of maladaptive beliefs (perceived social costs, perceived social self
      efficacy, and maladaptive interpersonal beliefs). Finally, implicit beliefs
      continued to predict social anxiety symptoms at 12 months post-treatment. These
      findings suggest that changes in patients' beliefs about their emotions may play
      an important role in CBT for SAD.

PMID- 25380180
TI  - Tailoring the Ti surface via electropolishing nanopatterning as a route to obtain
      highly ordered TiO2 nanotubes.
AB  - Highly ordered TiO2 nanotubes (NTs) were synthesized by the electrochemical
      anodization of Ti foils subjected to electropolishing (EP) pre-treatment. We
      found that the Ti surface roughness plays an important role in the onset of pore
      nucleation in enhancing the local focusing effect of the electrical field.
      Additionally, EP induces the formation of dimple structures on the metal surface,
      which can work as a pre-pattern prior to anodization. These shallow ripples lead
      to a preferentially ordered pore nucleation, offering an organizational
      improvement of the anodic oxide NTs. We found that, depending on the EP applied
      potential, the roughness and the spatial period of the ripple-like structures
      varies from 8-2 nm and from 122-30 nm, respectively. Such tuning allowed us to
      focus on the influence of the initial Ti pre-surface topography features on the
      NTs' length, organization, and hexagonal arrangement quality, as well as diameter
      and density. Our results show that an EP under 10 V is the most suitable to
      obtain a small Ti surface roughness, the largest NT length (40% enhancement), and
      the effective improvement of the ordered hexagonal NTs' arrays over larger areas.
      Furthermore, the NTs' dimensions (pore diameters and density) were also found to
      depend on the initial Ti surface topography. The use of optimized EP allows us to
      obtain highly hexagonal self-ordered samples at a reduced time and cost. 

PMID- 25380181
TI  - The effect of the periodic boundary conditions of a ZnO-coated nanospring on its
      surface redox-induced electrical response.
AB  - A redox chemical sensor (chemiresistor) was constructed with a single ZnO coated
      silica nanospring. The chemiresistor response to toluene vapor as a function of
      the sensor temperature (T(NS)) and vapor temperature (T(V)) was measured and
      analyzed. The maximum sensitivity of the single ZnO coated nanospring device
      occurred at the sensor temperature (T(NS)) of 310  degrees C and at the vapor
      temperature (T(V)) of 250  degrees C. The characteristics of the electrical
      response of a single ZnO coated nanospring device were compared to those of a ZnO
      thin film. The single ZnO nanospring sensor was less responsive to small changes
      in toluene concentration relative to the ZnO thin film, but has a lower ultimate
      detection level. A computational model to simulate an electrical response of the
      single nanospring sensor and the thin film indicated that the differences between
      their response characteristics is due to the geometry of the nanospring and
      corresponding periodic boundary conditions imposed by the nanospring geometry,
      which is absent in a thin film.

PMID- 25380182
TI  - In-vitro activation of natural killer cells from regional lymph nodes of melanoma
      patients with interleukin-2 and interleukin-15.
AB  - Regional lymph nodes (LNs) represent the first barrier in lymphogenic tumor
      dissemination in melanoma. Natural killer (NK) cells, the effector cell
      subpopulation of the innate immune system, are in the first line of antitumor
      immune defense. Therefore, the aim of this study was to investigate the effect of
      interleukin (IL)-2 and IL-15, two cytokines with similar immune-enhancing
      effects, on antitumor cytotoxic function and immunophenotype of NK cells from
      regional LNs of melanoma patients. Mononuclear cells purified from regional LNs
      of 50 melanoma patients in clinical stage II-IV were treated in vitro for 72 h
      and 7 days with 200 IU/ml rhIL-2 and 25 ng/ml IL-15 at 37 degrees C in 5% CO2.
      Both cytokines significantly augmented NK cell cytotoxic activity, transcription
      of the cytotoxic molecule perforin, and the level of functionally mature perforin
      in both nonmetastatic and metastatic regional LNs. IL-2 treatment increased the
      percentage of CD3CD56 NK cells by increasing the CD56 NK cell subset in both
      nonmetastatic and metastatic LNs, whereas IL-15 treatment did not affect the
      percentage of NK cells and their subsets. Both cytokines increased on NK cells
      from nonmetastatic and metastatic LNs the expression of CD69 early activation
      antigen, the NKG2D activating receptor, as well as CD16 and inhibitory killer
      cell immunoglobulin-like receptor CD158b, both inherent to the mature and the
      cytotoxic NK cell phenotype. In conclusion, our data may indicate the therapeutic
      potential of the NK cell population from regional LNs either as immunotherapeutic
      targets or as adoptively transferred after activation with IL-2 or IL-15. 

PMID- 25380183
TI  - Eruptive naevi in a patient treated with LGX818 for BRAF mutant metastatic
      melanoma.
AB  - LGX818 is a new-generation BRAF inhibitor (BRAFi) that is currently undergoing
      phase 3 trials for the treatment of BRAF mutant metastatic melanoma patients
      (NCT01909453). Cutaneous toxicities associated with the administration of BRAF
      inhibitors are considered to be induced by the paradoxical activation of the
      mitogen-activated protein kinase pathway in wild-type BRAF cells. Changes in
      naevi, including new naevi, hyperpigmentation and fading of existing naevi, have
      also been reported. In addition, some patients receiving these therapies have
      developed second primary melanomas. As a consequence, the importance of
      sequential digital dermoscopy in all patients treated with a BRAFi to detect new
      primary melanomas has been emphasized. A 61-year-old man with BRAF mutant stage
      IV metastatic melanoma was commenced on the phase 1 trial of LGX818 at 300 mg
      daily in 2013. After 2 months of therapy, the patient was noted to have developed
      eruptive naevi, fading of existing naevi and darkening of other naevi. Excision
      of a new pigmented lesion from the back indicated a compound naevus.
      Immunohistochemistry showed that the naevus cells lacked a BRAF V600E mutation.
      This is the first reported case of eruptive naevi in a patient treated with
      LGX818. The absence of the BRAF V600E mutation within a changing naevus supports
      the theory that BRAFi stimulates the proliferation of wild-type BRAF cells. Close
      dermatological surveillance is important for all patients treated with any type
      of BRAFi. 

PMID- 25380184
TI  - Elemental analogues of graphene: silicene, germanene, stanene, and phosphorene.
AB  - The fascinating electronic and optoelectronic properties of free-standing
      graphene has led to the exploration of alternative two-dimensional materials that
      can be easily integrated with current generation of electronic technologies. In
      contrast to 2D oxide and dichalcogenides, elemental 2D analogues of graphene,
      which include monolayer silicon (silicene), are fast emerging as promising
      alternatives, with predictions of high degree of integration with existing
      technologies. This article reviews this emerging class of 2D elemental materials 
      silicene, germanene, stanene, and phosphorene--with emphasis on fundamental
      properties and synthesis techniques. The need for further investigations to
      establish controlled synthesis techniques and the viability of such elemental 2D
      materials is highlighted. Future prospects harnessing the ability to manipulate
      the electronic structure of these materials for nano- and opto-electronic
      applications are identified.

PMID- 25380185
TI  - The value of diffusion tensor imaging in differentiating high-grade gliomas from
      brain metastases: a systematic review and meta-analysis.
AB  - PURPOSE: Differentiation of high-grade gliomas and solitary brain metastases is
      an important clinical issue because the treatment strategies differ greatly. Our
      study aimed to investigate the potential value of diffusion tensor imaging (DTI)
      in differentiating high-grade gliomas from brain metastases using a meta-analytic
      approach. MATERIALS AND METHODS: We searched Pubmed, Embase and the Cochrane
      Library for relevant articles published in English. Studies that both
      investigated high-grade gliomas and brain metastases using DTI were included.
      Random effect model was used to compare fractional anisotropy (FA) and mean
      diffusivity (MD) values in the two tumor entities. RESULTS: Nine studies were
      included into the meta-analysis. In the peritumoral region, compared with brain
      metastases, high-grade gliomas had a significant increase of FA (SMD  = 0.47; 95%
      CI, 0.22-0.71; P<0.01) and a significant decrease of MD (SMD  = -1.49; 95% CI, 
      1.91 to -1.06; P<0.01). However, in the intratumoral area, no significant change
      in FA (SMD  = 0.16; 95% CI, -0.49 to 0.82; P = 0.73) or MD (SMD  = 0.34; 95% CI, 
      0.91 to 1.60; P = 0.59) was detected between gliomas and metastases. CONCLUSIONS:
      High-grade gliomas may be distinguished from brain metastases by comparing the
      peritumoral FA and MD values. DTI appears to be a promising tool in diagnosing
      solitary intracranial lesions.

PMID- 25380186
TI  - Neurological outcomes associated with low-level manganese exposure in an
      inception cohort of asymptomatic welding trainees.
AB  - OBJECTIVE: Long-term, high-level exposure to manganese (Mn) is associated with
      impaired central nervous system (CNS) function. We quantitatively explored
      relations between low-level Mn exposure and selected neurological outcomes in a
      longitudinal inception cohort of asymptomatic welder trainees. METHODS: Welders
      with no previous occupational Mn exposure were observed approximately every three
      months over the course of the five-quarter traineeship. Fifty-six welders were
      assessed for motor function using the Unified Parkinson Disease Rating Scale
      motor subsection part 3 (UPDRS3) and Grooved Pegboard tests. A subset of 17 also
      had MRI scans to assess T1-weighted indices. Personal exposure to Mn in welding
      fume was quantitatively assessed during the study period using a mixed model to
      obtain estimates of subject-specific exposure level by welding type. These
      estimates were summed to estimate cumulative exposure at the time of each
      neurological outcome test. RESULTS: When adjusting for possible learning effects,
      there were no associations between cumulative exposure and UPDRS3 score or
      Grooved Pegboard time. T1-weighted indices of the basal ganglia (caudate,
      anterior putamen, posterior putamen, and combined basal ganglia, but not the
      pallidal index) exhibited statistically significant increases in signal intensity
      in relation to increased cumulative Mn exposure. CONCLUSIONS: This study
      demonstrates that T1-weighted changes can be detected in the brain even at very
      low levels of exposure among humans before any clinically evident deficits. This
      suggests that with continued follow-up we could identify a T1 threshold of
      toxicity at which clinical symptoms begin to manifest.

PMID- 25380187
TI  - Long term storage of dry versus frozen RNA for next generation molecular studies.
AB  - The standard method for the storage and preservation of RNA has been at ultra-low
      temperatures. However, reliance on liquid nitrogen and freezers for storage of
      RNA has multiple downsides. Recently new techniques have been developed for
      storing RNA at room temperature utilizing desiccation and are reported to be an
      effective alternative for preserving RNA integrity. In this study we compared
      frozen RNA samples stored for up to one year to those which had been desiccated
      using RNAstable (Biomatrica, Inc., San Diego, CA) and stored at room temperature.
      RNA samples were placed in aliquots and stored after desiccation or frozen (at 
      80 degrees C), and were analyzed for RNA Integrity Number (RIN), and by qPCR, and
      RNA sequencing. Our study shows that RNAstable is able to preserve desiccated RNA
      samples at room temperature for up to one year, and that RNA preserved by
      desiccation is comparable to cryopreserved RNA for downstream analyses including
      real-time-PCR and RNA sequencing. 

PMID- 25380189
TI  - Effect of permafrost properties on gas hydrate petroleum system in the Qilian
      Mountains, Qinghai, Northwest China.
AB  - The gas hydrate petroleum system in the permafrost of the Qilian Mountains, which
      exists as an epigenetic hydrocarbon reservoir above a deep-seated hydrocarbon
      reservoir, has been dynamic since the end of the Late Pleistocene because of
      climate change. The permafrost limits the occurrence of gas hydrate reservoirs by
      changing the pressure-temperature (P-T) conditions, and it affects the migration
      of the underlying hydrocarbon gas because of its strong sealing ability. In this
      study, we reconstructed the permafrost structure of the Qilian Mountains using a
      combination of methods and measured methane permeability in ice-bearing sediment
      permafrost. A relationship between the ice saturation of permafrost and methane
      permeability was established, which permitted the quantitative evaluation of the
      sealing ability of permafrost with regard to methane migration. The test results
      showed that when ice saturation is >80%, methane gas can be completely sealed
      within the permafrost. Based on the permafrost properties and genesis of shallow
      gas, we suggest that a shallow "gas pool" occurred in the gas hydrate petroleum
      system in the Qilian Mountains. Its formation was related to a metastable gas
      hydrate reservoir controlled by the P-T conditions, sealing ability of the
      permafrost, fault system, and climatic warming. From an energy perspective, the
      increasing volume of the gas pool means that it will likely become a shallow gas
      resource available for exploitation; however, for the environment, the gas pool
      is an underground "time bomb" that is a potential source of greenhouse gas. 

PMID- 25380190
TI  - Neurochemical characterization of extrinsic nerves in myenteric ganglia of the
      guinea pig distal colon.
AB  - Extrinsic nerves to the gut influence the absorption of water and electrolytes
      and expulsion of waste contents, largely via regulation of enteric neural
      circuits; they also contribute to control of blood flow. The distal colon is
      innervated by extrinsic sympathetic and parasympathetic efferent and spinal
      afferent neurons, via axons in colonic nerve trunks. In the present study,
      biotinamide tracing of colonic nerves was combined with immunohistochemical
      labeling for markers of sympathetic, parasympathetic, and spinal afferent neurons
      to quantify their relative contribution to the extrinsic innervation. Calcitonin
      gene-related peptide, vesicular acetylcholine transporter, and tyrosine
      hydroxylase, which selectively label spinal afferent, parasympathetic, and
      sympathetic axons, respectively, were detected immunohistochemically in 1 +/-
      0.5% (n = 7), 15 +/- 4.7% (n = 6), and 24 +/- 4% (n = 7) of biotinamide-labeled
      extrinsic axons in myenteric ganglia. Immunoreactivity for vasoactive intestinal
      polypeptide, nitric oxide synthase, somatostatin, and vesicular glutamate
      transporters 1 and 2 accounted for a combined maximum of 14% of biotinamide
      labeled axons in myenteric ganglia. Thus, a maximum of 53% of biotinamide-labeled
      extrinsic axons in myenteric ganglia were labeled by antisera to one of these
      eight markers. Viscerofugal neurons were also labeled by biotinamide. They had
      distinct morphologies and spatial distributions that correlated closely with
      their immunoreactivity for nitric oxide synthase and choline acetyltransferase.
      As reported for the rectum, nearly half of all extrinsic nerve fibers to the
      distal colon lack the key immunohistochemical markers commonly used for their
      identification. Their abundance may therefore have been significantly
      underestimated in previous immunohistochemical studies.

PMID- 25380191
TI  - Aspirin and NSAIDs for breast cancer chemoprevention.
AB  - Novel treatment strategies are needed for breast cancer chemoprevention.
      Tamoxifen is the only drug approved for the chemoprevention of estrogen receptor
      positive breast cancer. However, to date, no treatment exists for the
      chemoprevention of estrogen receptor-negative breast cancer. NSAID use is
      associated with a reduced risk of breast cancer. However, the biological
      mechanisms underlying the effect of NSAID on breast cancer are not well defined.
      NSAIDs inhibit cyclooxygenases, thus preventing the formation of prostaglandins,
      prostacyclin, and thromboxane. NSAIDs also exert other biological effects,
      including generation of reactive oxygen species and inhibition of nuclear factor
      kappaB-mediated signals. This review synthesizes the evidence on the COX-2
      independent mechanisms of action of aspirin, salicylates, and other NSAIDs on
      breast cancer. 

PMID- 25380192
TI  - Prevalence of colorectal adenoma in an average-risk population aged 40-50 versus
      50-60 years.
AB  - According to current guidelines, screening colonoscopy begins at 50 years for the
      average-risk population, although there are not enough data on the incidence of
      precancerous lesions of individuals in the preceding decades. To evaluate the
      prevalence of colorectal polyps including potentially premalignant lesions in
      asymptomatic, average-risk individuals aged 40-49 versus 50-59 years, we offered
      total colonoscopy screening to individuals without any lower gastrointestinal
      symptoms. The primary end point was the prevalence of colorectal adenoma in two
      age groups. Of a total of 737 studies, 333 participants were 40-49 years old and
      407 participants were 50-59 years old. The overall prevalence of adenomas was
      11.2 and 16.4% in the group of 40-49 and 50-59 year olds, respectively. Advanced
      adenoma was more common in 50-59 year olds (1.2 vs. 2.9%). Malignancy was not
      reported in these groups. Furthermore, 77.5 and 68.6% of adenomas were observed
      in the distal colon in the groups of 40-49 year olds and 50-59 year olds, whereas
      in the proximal colon, 22.2 and 57.1% of adenomas in the groups of 40-49 year
      olds and 50-59 year olds, respectively, were advanced adenomas. In our study,
      male sex showed an association with adenoma. However, importantly, there was no
      significant association between age and colorectal adenoma. Although the
      prevalence of colorectal adenoma was similar in the two age groups investigated,
      the rate of advanced adenoma was higher in the group of individuals who were 50
      59 years old, suggesting that colorectal cancer screening could be recommended at
      an age younger than 50 years. 

PMID- 25380193
TI  - Safety, tolerability, and plasma exposure of tiotropium Respimat(r) in children
      and adults with cystic fibrosis.
AB  - BACKGROUND: People with cystic fibrosis (CF) suffer from chronic lung disease
      that is often treated with a bronchodilator. This trial evaluated the
      pharmacokinetics, safety, and tolerability of single and multiple doses of
      tiotropium inhaled via the Respimat(r) Soft MistTM Inhaler in patients with CF.
      METHODS: Patients received a single dose (placebo, 2.5 MUg, 5 MUg, or 10 MUg)
      and/or multiple doses (placebo, 2.5 MUg, or 5 MUg) of tiotropium daily for 28
      days. RESULTS: Ninety-two patients, aged 5-57 years, were treated. All doses
      showed a satisfactory safety profile for adverse events, vital signs, laboratory
      evaluations, and physical examination. At steady-state, peak exposure to
      tiotropium was comparable between adult patients with CF and patients with
      chronic obstructive pulmonary disease. CONCLUSIONS: Tiotropium 2.5 MUg or 5 MUg
      inhaled via the Respimat(r) Soft MistTM Inhaler once daily was well tolerated in
      patients with CF.

PMID- 25380197
TI  - Effects of maternal deprivation and the duration of reunion time on rat pup
      ultrasonic vocalization responses to isolation: possible implications for human
      infant studies.
AB  - In a paradigm that may serve as a translational model for maternal separation
      experiences of human infants in neonatal intensive care units, we examined how
      the duration of reunion with the dam influenced the phenomenon of maternal
      potentiation of ultrasonic vocalizations, in which isolated rat pups increase
      rates of vocalization following brief interactions with dams. We report that
      maternal potentiation in 12-13 day-old rats did not occur after reunions with
      their anesthetized dam that lasted longer than 15-min. However, after 18 hr
      maternal separation, isolated pups given reunions with their anesthetized dam
      increased vocalization rate even with reunions as long as 3 hr. Using a split
      cage apparatus that prevented physical contact, the impact of 18 hr separations
      on maternal potentiation was partially offset by experiencing olfactory and/or
      auditory stimuli of the mother. These results suggest that maintaining partial
      maternal sensory exposure during prolonged maternal separation can reduce
      responses elicited by subsequent maternal separation.

PMID- 25380194
TI  - Designing mental health interventions informed by child development and human
      biology theory: a social ecology intervention for child soldiers in Nepal.
AB  - The anthropological study of human biology, health, and child development
      provides a model with potential to address the gap in population-wide mental
      health interventions. Four key concepts from human biology can inform public
      mental health interventions: life history theory and tradeoffs, redundancy and
      plurality of pathways, cascades and multiplier effects in biological systems, and
      proximate feedback systems. A public mental health intervention for former child
      soldiers in Nepal is used to illustrate the role of these concepts in
      intervention design and evaluation. Future directions and recommendations for
      applying human biology theory in pursuit of public mental health interventions
      are discussed.

PMID- 25380199
TI  - 17beta-estradiol causes abnormal development in embryos of the viviparous
      eelpout.
AB  - Elevated frequencies of malformations among the offspring of Baltic eelpout
      (Zoarces viviparus) have been observed in aquatic environments receiving high
      anthropogenic input suggesting that manmade chemicals could be the causative
      agent. However, causal links between exposure to chemicals and abnormal
      development have never been confirmed in laboratory experiments. The purpose of
      this study was to investigate if exposure to 17beta-estradiol (E2) causes
      abnormal development in larvae of the viviparous eelpout. Wild female eelpout
      were collected immediately after fertilization and exposed to E2 concentrations
      ranging from 5.7 to 133 ng L(-1) for 6 weeks in a flow through test system. The
      experiment shows that E2 concentrations of 53.6 and 133 ng L(-1) cause severe
      abnormal development among eelpout embryos. Reduced amount of ovarian fluid and
      increased weight of the ovarian sac indicate disturbance of ovarian function.
      Female plasma concentrations of E2 and vitellogenin increase in a monotonic
      concentration-response relationship with significant induction in the low
      concentration range. Our findings support the plausibility that the abnormal
      development among eelpout embryos encountered in monitoring programs may actually
      be caused by exposure to chemicals in the environment. 

PMID- 25380198
TI  - Coculture of stem cells from apical papilla and human umbilical vein endothelial
      cell under hypoxia increases the formation of three-dimensional vessel-like
      structures in vitro.
AB  - The success of bioengineered dental pulp depends on two principles, (1) whether
      the transplanted tissue can develop its own vascular endothelial tubule network
      and (2) whether the host vasculature can be induced to penetrate the
      bioengineered pulp replacement and conjoin. Major inductive molecules that
      participate in laying down blood vessels include vascular endothelial growth
      factor (VEGF), ephrinB2, and hypoxia-inducible factor 1alpha (HIF-1alpha). Being
      able to modulate the genes encoding these angiogenic molecules is a therapeutic
      target in pulp regeneration for endogenous blood vessel formation, prevention of
      graft rejection, and exclusion of infection. Once implanted inside the root
      canal, bioengineered pulp is subjected to severe hypoxia that causes tissue
      degeneration. However, short-term hypoxia is known to stimulate angiogenesis.
      Thus, it may be feasible to prime dental cells for angiogenic activity before
      implantation. Stem cells from apical papilla (SCAP) are arguably one of the most
      potent and versatile dental stem cell populations for bioengineering pulp in
      vitro. Our study aimed to investigate whether coculture of SCAP and human
      umbilical vein endothelial cells (HUVECs) under hypoxia promotes the formation of
      endothelial tubules and a blood vessel network. In addition, we clarified the
      interplay between the genes that orchestrate these important angiogenic molecules
      in SCAP under hypoxic conditions. We found that SCAP cocultured with HUVEC at a
      1:5 ratio increased the number of endothelial tubules, tubule lengths, and
      branching points. Fluorescence staining showed that HUVEC formed the trunk of
      tubular structures, whereas SCAP located adjacent to the endothelial cell line,
      resembling the pericyte location. When we used CoCl2 (0.5 mM) to induce hypoxic
      environment, the expression of proteins, HIF-1alpha and VEGF, and transcript of
      ephrinB2 in SCAP was upregulated. However, minimal VEGF levels in supernatants of
      HUVEC and coculture Petri dishes were detected, suggesting that VEGF secreted by
      SCAP might be used by HUVEC to accelerate the formation of vessel-like
      structures. Taken together, we revealed that artificial hypoxia stimulates
      angiogenic responses in SCAP for possible use in engineering dental pulp
      replacements. Our results may help to delineate the optimal therapeutic target to
      promote angiogenesis so that future bioengineered pulp replacements integrate
      faster and permanently within the host. 

PMID- 25380201
TI  - [Obesity and gastrointestinal neoplasms].
AB  - Being overweight or obese is a significant public health problem in the 21st
      century due to its scale, common existence and its cause-effect association with
      multiple diseases. Excessive accumulation of adipose tissue in humans is regarded
      as a major risk factor for development of cardiovascular and skeletal diseases.
      However, data from recent years have revealed that obesity is also strongly
      associated with increased risk of the majority of cancers in humans, including
      those originating from the gastrointestinal tract. During the last few year this
      association has been thoroughly proven and supported by several epidemiological
      analyses. The authors present i) the current state of knowledge regarding key
      (patho)mechanisms that link metabolism of human adipose tissue to
      development/progression of neoplasms (especially in the gastrointestinal tract),
      as well as ii) the results of selected clinical studies in which the influence of
      obesity on risk of gastrointestinal cancer development has been addressed. 

PMID- 25380202
TI  - [Fish intake and risk of prostate cancer].
AB  - The aim of the study was to present the current state of knowledge concerning the
      relationship between the consumption of fish as materials rich in long chain
      polyunsaturated fatty acids (LC PUFA) omega-3, and the risk of prostate cancer.
      Many scientific reports confirm the health benefits from the consumption of fish
      and protective properties of LC PUFA omega-3 in relation to prostate cancer.
      However, there are reports that indicate a relationship of the high consumption
      of PUFA with the risk of prostate cancer. The way of processing and preservation
      of the fish, and other factors not included in previous studies, could have some
      importance in the etiology of this disease. High susceptibility of PUFA to
      oxidation changes and the technological fish processing (smoking, high
      temperature cooking methods) contribute to the formation of many compounds, such
      as polycyclic aromatic hydrocarbons and heterocyclic amines - which may influence
      the formation of cancers - including prostate cancer. It is necessary to ensure
      an adequate amount of LC PUFA omega-3 in the diet through the consumption of
      proper quality fish and fish oils. Particular attention should be paid to the
      high susceptibility of PUFA to the oxidative processes, and the method of
      processing, preservation and storage of fish. Also pollution from the environment
      can significantly reduce the impact of health benefits of PUFA and fish, and even
      be the cause of cancers, including prostate cancer. Further research in this area
      should be more targeted to assess the impact of nutritional factors for the
      development of such tumors. 

PMID- 25380200
TI  - Relationships between bacterial community composition, functional trait
      composition and functioning are context dependent--but what is the context?
AB  - Bacterial communities are immensely diverse and drive many fundamental ecosystem
      processes. However, the role of bacterial community composition (BCC) for
      functioning is still unclear. Here we evaluate the relative importance of BCC
      (from 454-sequencing), functional traits (from Biolog Ecoplates) and
      environmental conditions for per cell biomass production (BPC; 3H-leucine
      incorporation) in six data sets of natural freshwater bacterial communities. BCC
      explained significant variation of BPC in all six data sets and most variation in
      four. BCC measures based on 16S rRNA (active bacteria) did not consistently
      explain more variation in BPC than measures based on the 16S rRNA-gene (total
      community), and adding phylogenetic information did not, in general, increase the
      explanatory power of BCC. In contrast to our hypothesis, the importance of BCC
      for BPC was not related to the anticipated dispersal rates in and out of
      communities. Functional traits, most notably the ability to use cyclic and
      aromatic compounds, as well as local environmental conditions, i.e.
      stoichiometric relationships of nutrients, explained some variation in all six
      data sets. In general there were weak associations between variation in BCC and
      variation in the functional traits contributing to productivity. This indicates
      that additional traits may be important for productivity as well. By comparing
      several data sets obtained in a similar way we conclude that no single measure of
      BCC was obviously better than another in explaining BPC. We identified some key
      functional traits for productivity, but although there was a coupling between
      BCC, functional traits and productivity, the strength of the coupling seems
      context dependent. However, the exact context is still unresolved. 

PMID- 25380203
TI  - [Selected biological markers in various vascular lesions of the head and neck].
AB  - Vascular anomalies are divided according to the contemporary system of
      classification into two groups: tumors and malformations. However, there is no
      consensus on juvenile angiofibroma's place in that system. The general
      characteristics of selected markers of angiogenesis and tissue remodeling are
      presented in the series in the context of current knowledge in the field of
      pathophysiology of vascular lesions. The mentioned markers are currently the
      subjects of multidirectional studies in oncology, as they take part in the
      process of neoangiogenesis and proliferation of tumors. Nevertheless, they have
      not been widely examined in vascular lesions. The indirect goal of that series is
      to indicate the possible research direction on vascular lesions to determine
      their molecular profile, to create a more specific system of classification, and
      above all to develop new diagnostic and treatment methods. 

PMID- 25380204
TI  - [Immunostimulatory properties of mistletoe extracts and their application in
      oncology].
AB  - For a long time cancer immunotherapy was overshadowed by chemotherapy and
      radiotherapy. Recently, "Science", one of the world's top scientific journals,
      named the stimulation of the body's own immune system to fight cancer cells as
      the "breakthrough of the year". In Germany, Switzerland and Austria, extracts
      derived from mistletoe (Viscum album L.) such as Iscador, Abnobaviscum, Helixor,
      Iscar, Iscucin and Isorel have been used in oncology for many years. These
      extracts have immunomodulating and immunostimulating properties, as demonstrated
      by experimental studies as well as in clinical trials. The aim of our paper is to
      present immunological disorders associated with cancer, which can be counteracted
      by treatment with extracts derived from mistletoe. Although these drugs cannot
      replace conventional cancer treatment, they may improve the patient's quality and
      length of life. 

PMID- 25380205
TI  - Superfamily of G-protein coupled receptors (GPCRs)--extraordinary and outstanding
      success of evolution.
AB  - The G protein-coupled receptors (GPCRs) are considered as very diverse and also
      surprisingly successful structures during the whole evolutionary process, being
      capable of transducing the different forms of "information" within the cell and
      also between cells, such as different peptides, lipids, proteins, nucleotides,
      nucleosides, organic odorants and photons. Complex studies as well as two
      dimensional crystallization of rhodopsin, their paradigm, led to the creation of
      a useful model having a common central core, consisting of seven transmembrane
      helical domains, which undergoes appropriate structural modification during
      activation and signal transduction. After the complete delineation of the human
      genome, which is the apogee of human scientific civilization and culture, it was
      possible to identify more than 800 human GPCR sequences and in parallel analyze
      342 unique functional nonolfactory human GPCR sequences with phylogenetic
      analyses. These results support, with high bootstrap values, the existence of
      five main families, named by the authors glutamate, rhodopsin, adhesion,
      frizzle/taste2, and secretin, forming the GRAFS classification system. Positions
      of the GPCRs in chromosomal paralogous regions indicate the importance of
      tetraploidizations or local gene duplication events during their creation. Some
      families of GPCRs show, however, very little or no similarity in the sequence of
      amino acid chains. They utilize an enormous number of different domains to bind
      ligands and to activate the appropriate G-proteins. The delicate tuning of their
      coupling to G proteins is further regulated by splicing, RNA editing and
      phosphorylation. A number of GPCRs may also form homodimers or heterodimers with
      structurally different GPCRs and also with membrane-bound proteins having one
      transmembrane domain. It should also be stressed that not all GPCRs are strictly
      faithful to G proteins because growing evidence indicates that they can interact
      directly, via their C-terminal domain, with proteins containing PDZ domains,
      which are present in the PDZ proteins. These proteins organize the NMDA receptors
      and some K+ channels while their PDZ domains generally bind 3-4 amino-acid
      stretches of C-terminal sequences of target proteins. The -S/TXV motif was found
      in some PDZ target proteins. GPCRs can also interact with the Enabled/VASP
      homology (EVH)-like domain which interacts directly with group 1 mGluR receptors.
      Every year brings new very important data in research of these proteins, which
      should be called "the most successful structures evolved during the whole of
      animal evolution". 

PMID- 25380206
TI  - [Conjugated linolenic acids (CLnA, super CLA)--natural sources and biological
      activity].
AB  - Polyunsaturated fatty acids (PUFA) have a wide range of biological activity.
      Among them conjugated fatty acids are of great interest. Conjugated linoleic
      acids (CLA), which exert a multidirectional health-benefiting influence, and
      conjugated linolenic acids (CLnA, super CLA) are examples of this group of fatty
      acids. CLnA are a group of positional and geometric isomers of octadecatrienoic
      acid (C18:3), which possess double bonds at positions 9, 11, 13 or 8, 10, 12 of
      their chain. Some vegetable oils are rich sources of CLnA, e.g. bitter melon oil
      (from Momordica charantia seeds) and pomegranate oil (from Punica granatum
      seeds). The aim of this paper was to present information concerning natural
      sources and health-promoting activities of conjugated linolenic acids. The
      presented data reveal that conjugated linolenic acids may be very useful in
      prevention and treatment of many diseases, especially diabetes, arteriosclerosis
      , obesity and cancers (mammary, prostate and colon cancer). Among many potential
      mechanisms of their action, the fact that some CLnA are converted by
      oxidoreductases into CLA is very important. It seems to be very reasonable to
      conduct research concerning the possibility of CLnA use in prevention of many
      diseases. 

PMID- 25380207
TI  - [The role of Escherichia coli strain Nissle 1917 in the gastro-intestinal
      diseases].
AB  - In this paper a review of the researches on the role of Escherichia coli strain
      Nissle 1917 (EcN) in gastrointestinal diseases was presented. EcN is a non
      pathogenic strain of the Enterobacteriaceae family, which has probiotic
      properties. In a number of studies conducted among humans and  experimental
      animals the application of EcN in treatment of gastrointestinal diseases was
      observed. Most studies about EcN has been devoted to this organism efficacy in
      ulcerative colitis treatment. Comparable results were obtained, by citied
      authors, in the treatment (sustaining remission) of EcN and mesalazine in
      ulcerative colitis. Moreover, this probiotic therapy, compared to placebo,
      contributes to obtaining a faster remission and improvement of intestinal
      histopathology. The use of EcN in Crohn's disease has not been the subject of as
      many studies as in the case of ulcerative colitis. Assessing the importance of
      EcN in treatment of other gastrointestinal disorders, authors of the studies
      observed, that in patients with irritable bowel syndrome, who receiving this
      probiotic there was a pain, nausea and bloating reduction. In studies conducted
      among children a positive impact of EcN in prevention and treatment of diarrhea
      was demonstrated. Similar results were obtained in studies conducted in
      experimental animals. Based on the presented review it can be concluded that the
      strain of Escherichia coli Nissle 1917 is useful in treatment of gastrointestinal
      diseases, especially in treatment of ulcerative colitis. This probiotic may
      constitute a part of treatment of irritable bowel syndrome and diarrhea. The
      effectiveness of this strain in treatment of Crohn's disease is not clearly
      established and further research are require. 

PMID- 25380208
TI  - Association and family studies of DRD2 gene polymorphisms in alcohol dependence
      syndrome.
AB  - INTRODUCTION: The human dopamine receptor 2 gene DRD2 plays a central role in
      susceptibility to Alcohol Dependence Syndrome (ADS). The aim of this study was to
      evaluate 3 single nucleotide polymorphisms: D2 (rs1076560), Tag1D (rs1800498),
      Tag1B (rs1079597) located in dopamine receptor 2 DRD2 gene and its role in
      alcohol dependence. MATERIAL AND METHODS: DNA was provided from alcohol dependent
      (AD) patients (n=171) and healthy control subjects (n=160) all of Polish descent.
      The history of alcoholism was obtained using the Polish version of the SSAGA
      (Semi-Structured Assessment for the Genetics of Alcoholism). We conducted case
      control association study and transmission disequilibrium test (TDT). Samples
      were genotyped using real-time PCR method. RESULTS: We did not confirm the
      association between studied polymorphisms and alcohol dependence syndrome. TDT
      reveled an adequate transmission of both alleles in the group of alcohol
      families. CONCLUSIONS: The lack of association of studied polymorphisms and ADS
      does not preclude its participation in the pathogenesis. Further research is
      needed to determine the actual contribution of DRD2 gene in the pathogenesis of
      alcoholism.

PMID- 25380209
TI  - [Perspectives on the pharmacotherapy of diseases extending with advanced
      oxidation protein products participation].
AB  - In the view of constantly increasing number of reports about participation of
      advanced oxidation protein products (AOPPs) in pathogenesis of many diseases as
      well as in the pathomechanism of their biochemical disturbances and clinical
      complications, the possibility of treatment of these diseases by reducing of
      AOPPs concentration and prevention or inhibition of their formation poses the
      object of intensive investigations. The first investigated agents, with proven
      efficacy in prevention of AOPPs formation, was N-acetylcysteine. In relationship
      with the fact, that the intensified formation of AOPPs is closely connected with
      intensity of oxidative stress (OS), so the possibility of use of agents and/or
      drugs with well-known antioxidative proprieties, also natural origin, was
      examined. It is very important in aspects of its self-treatment by patients. The
      next step was the estimation of possibility of utilization of pleiotropic
      properties of drugs routinely applied in the treatment of civilization diseases,
      especially hypertension and diabetes, often with kidneys insufficiency. On the
      basis of known mechanism of the unfavorable acting of AOPPs (induction of
      intracellular signal transduction, and secondary intensyfication of OS), on the
      way of its connection with the RAGE receptor [similarly as advanced glycation end
      products (AGEs)], indicated on the possibility of new therapeutic strategies,
      through the blocking of RAGE-AGEs interactions or using the soluble form of this
      receptor. Discussed in this paper results of investigations shows the possibility
      to introduction in the near future, the innovative therapeutic strategies,
      directed just on the AOPPs, permitting on the limitation of their formation and
      accumulation in tissues and organs, especially in kidneys. This will permit for
      the break of mechanism of vicious circle of interaction OS and oxidatively
      modified macromolecules and attenuating of biochemical and clinical disturbances
      in the diseases connected with AOPPs participating. 

PMID- 25380210
TI  - [Noncovalent cation-pi interactions--their role in nature].
AB  - Non-covalent interactions play an extremely important role in organisms. The main
      non-covalent interactions in nature are: ion-ion interactions, dipole-dipole
      interactions, hydrogen bonds, and van der Waals interactions. A new kind of
      intermolecular interactions--cation-pi interactions--is gaining increasing
      attention. These interactions occur between a cation and a pi system. The main
      contributors to cation-pi interactions are electrostatic, polarization and, to a
      lesser extent, dispersion interactions. At first, cation-pi interactions were
      studied in a gas phase, with metal cation-aromatic system complexes. The
      characteristics of these complexes are as follows: an increase of cation atomic
      number leads to a decrease of interaction energy, and an increase of cation
      charge leads to an increase of interaction energy. Aromatic amino acids bind with
      metal cations mainly through interactions with their main chain. Nevertheless,
      cation-pi interaction with a hydrophobic side chain significantly enhances
      binding energy. In water solutions most cations preferentially interact with
      water molecules rather than aromatic systems. Cation-pi interactions occur in
      environments with lower accessibility to a polar solvent. Cation-pi interactions
      can have a stabilizing role on the secondary, tertiary and quaternary structure
      of proteins. These interactions play an important role in substrate or ligand
      binding sites in many proteins, which should be taken into consideration when the
      screening of effective inhibitors for these proteins is carried out. Cation-pi
      interactions are abundant and play an important role in many biological
      processes.

PMID- 25380214
TI  - Dual relaxation and structural changes under uniaxial strain in main-chain
      smectic-C liquid crystal elastomer.
AB  - The relationship between strain-dependent macroscopic elastic behavior and the
      changes in microscopic structure of the smectic-C liquid crystal elastomer (LCE),
      C11MeHQSi8 were investigated using synchrotron X-ray studies. At very low strains
      epsilon <= 0.2, the smectic layers are randomly oriented. As the strain increases
      beyond 0.2, the smectic layers reorient and become parallel to the direction of
      the applied strain. The polydomain to monodomain (P-M) transition accompanied by
      the formation of chevron structure ensues for epsilon > 0.2 and is nearly
      complete for epsilon = 0.7. The chevron structure relaxes after the applied
      strain changes, with a time constant taualpha ~ 45 min while the orientation
      order parameters of the mesogenic and elastomeric components gradually increase
      and saturate at 0.83 and 0.4, respectively at epsilon = 1.7 which is near the end
      of the plateau region. Relaxation rates taualpha for the tilt angle and taud
      corresponding to the smectic layer spacing both become about 10 times faster when
      the strain exceeds 0.7. The LCE remains "locked" into the monodomain state and
      retains 90% and 80% values of alpha and S, respectively for 24 hours after the
      applied strain is removed. The viscoelastic properties of the liquid crystal
      appear to dominate the equilibration process at low strains while the elastomeric
      properties control the system's response at high strains. 

PMID- 25380215
TI  - Synthesis and evaluation of protein arginine N-methyltransferase inhibitors
      designed to simultaneously occupy both substrate binding sites.
AB  - The protein arginine N-methyltransferases (PRMTs) are a family of enzymes that
      function by specifically transferring a methyl group from the cofactor S-adenosyl
      L-methionine (AdoMet) to the guanidine group of arginine residues in target
      proteins. The most notable is the PRMT-mediated methylation of arginine residues
      that are present in histone proteins which can lead to chromatin remodelling and
      influence gene transcription. A growing body of evidence now implicates
      dysregulated PRMT activity in a number of diseases including various forms of
      cancer. The development of PRMT inhibitors may therefore hold potential as a
      means of developing new therapeutics. We here report the synthesis and evaluation
      of a series of small molecule PRMT inhibitors designed to simultaneously occupy
      the binding sites of both the guanidino substrate and AdoMet cofactor. Potent
      inhibition and surprising selectivity were observed when testing these compounds
      against a panel of methyltransferases.

PMID- 25380216
TI  - Excellent sun-light-driven photocatalytic activity by aurivillius layered
      perovskites, Bi5-xLaxTi3FeO15 (x = 1, 2).
AB  - Aurivillius phase layered perovskites, Bi5-xLaxTi3FeO15 (x = 1, 2) are
      synthesized by solid-state reaction. The compounds are characterized by powder X
      ray diffraction (PXD), field-emission scanning electron microscopy (FE-SEM),
      energy-dispersive X-ray spectroscopy (EDS), UV-vis diffuse reflectance (UV-vis
      DRS), and photoluminescence (PL) spectroscopy. UV-vis DRS data revealed that the
      compounds are visible light absorbing semiconductors with band gaps ranging from
      ~2.0-2.7 eV. Photocatalytic activity studies by Rhodamine B (RhB) degradation
      under sun-light irradiation showed that these layered oxides are very efficient
      photocatalysts in mild acidic medium. Scavenger test studies demonstrated that
      the photogenerated holes and superoxide radicals (O2(*-)) are the active species
      responsible for RhB degradation over the Aurivillius layered perovskites.
      Comparison of PL intensity, dye adsorption and zeta-potential suggested that a
      slow e(-)-h(+) recombination and effective dye adsorption are crucial for the
      degradation process over these photocatalysts. Moreover, relative positioning of
      the valence and conduction band edges of the semiconductors, O2/O2(*-), (*)OH/H2O
      potential and HOMO-LUMO levels of RhB appears to be responsible for making the
      degradation hole-specific. Photocatalytic cycle tests indicated high stability of
      the catalysts in the reaction medium without any observable loss of activity.
      This work shows great potential in developing novel photocatalysts with layered
      structures for sun-light-driven oxidation and degradation processes largely
      driven by holes and without any intervention of hydroxyl radicals, which is one
      of the most common reactive oxygen species (ROS) in many advanced oxidation
      processes. 

PMID- 25380217
TI  - Size effects on cation heats of formation. III. Methyl and ethyl substitutions in
      group IV XH4, X = C, Si, Ge, Sn, Pb.
AB  - The heats of formation of alkyl-substituted XH4 (X = C, Si, Ge, Sn, Pb)
      DeltafH(M(+)) = IEad(M) + DeltafH (M) molecular ions have often never been
      measured or are not known to better than 10 or 20 kJ/mol. The present study on
      these Main Group IV compounds adopts a graphical approach that relates cation
      heats of formation to cation size. A study of methyl substitution in XH4 is
      followed by a similar examination of heat of formation data on ethyl substitution
      in methane, silane, germane, stannane, and plumbane. The results provide tests of
      the validity of this graphical method as well as its use as a predictive tool for
      determining cation and neutral heats of formation. Suggestions are made of the
      need to investigate or reinvestigate the ionization energies and/or the heats of
      formation of several of the molecules studied. Results and conclusions are
      tabulated.

PMID- 25380218
TI  - Stacking disorder in ice I.
AB  - Traditionally, ice I was considered to exist in two well-defined crystalline
      forms at ambient pressure: stable hexagonal ice (ice Ih) and metastable cubic ice
      (ice Ic). However, it is becoming increasingly evident that what has been called
      cubic ice in the past does not have a structure consistent with the cubic crystal
      system. Instead, it is a stacking-disordered material containing cubic sequences
      interlaced with hexagonal sequences, which is termed stacking-disordered ice (ice
      Isd). In this article, we summarise previous work on ice with stacking disorder
      including ice that was called cubic ice in the past. We also present new
      experimental data which shows that ice which crystallises after heterogeneous
      nucleation in water droplets containing solid inclusions also contains stacking
      disorder even at freezing temperatures of around -15  degrees C. This supports
      the results from molecular simulations, that the structure of ice that
      crystallises initially from supercooled water is always stacking-disordered and
      that this metastable ice can transform to the stable hexagonal phase subject to
      the kinetics of recrystallization. We also show that stacking disorder in ice
      which forms from water droplets is quantitatively distinct from ice made via
      other routes. The emerging picture of ice I is that of a very complex material
      which frequently contains stacking disorder and this stacking disorder can vary
      in complexity depending on the route of formation and thermal history. 

PMID- 25380219
TI  - Predictors of six-month mortality among nursing home residents: diagnoses may be
      more predictive than functional disability.
AB  - OBJECTIVE: Loss of daily living functions can be a marker for end of life and
      possible hospice eligibility. Unfortunately, data on patient's functional
      abilities is not available in all settings. In this study we compare predictive
      accuracy of two indices designed to predict 6-month mortality among nursing home
      residents. One is based on traditional measures of functional deterioration and
      the other on patients' diagnoses and demography. METHODS: We created the Hospice
      ELigibility Prediction (HELP) Index by examining mortality of 140,699 Veterans
      Administration (VA) nursing home residents. For these nursing home residents, the
      available data on history of hospital admissions were divided into training
      (112,897 cases) and validation (27,832 cases) sets. The training data were used
      to estimate the parameters of the HELP Index based on (1) diagnoses, (2) age on
      admission, and (3) number of diagnoses at admission. The validation data were
      used to assess the accuracy of predictions of the HELP Index. The cross-validated
      accuracy of the HELP Index was compared with the Barthel Index (BI) of functional
      ability obtained from 296,052 VA nursing home residents. A receiver operating
      characteristic curve was used to examine sensitivity and specificity of the
      predicted odds of mortality. RESULTS: The area under the curve (AUC) for the HELP
      Index was 0.838. This was significantly (alpha <0.01) higher than the AUC for the
      BI of 0.692. CONCLUSIONS: For nursing home residents, comorbid diagnoses predict
      6-month mortality more accurately than functional status. The HELP Index can be
      used to estimate 6-month mortality from hospital data and can guide prognostic
      discussions prior to and following nursing home admission.

PMID- 25380220
TI  - Modeling and optimization of phospholipase A1-catalyzed hydrolysis of
      phosphatidylcholine using response surface methodology for
      lysophosphatidylcholine production.
AB  - Modeling the phospholipase A1 (PLA1 )-catalyzed partial hydrolysis of soy
      phosphatidylcholine (PC) in hexane for the production of lysophosphatidylcholine
      (LPC) and optimizing the reaction conditions using response surface methodology
      were described. The reaction was performed with 4 g of PC in a stirred batch
      reactor using a commercial PLA1 (Lecitase Ultra) as the biocatalyst. The effects
      of temperature, reaction time, water content, and enzyme loading on LPC and
      glycerylphosphorylcholine (GPC) content in the reaction products were elucidated
      using the models established. Optimal reaction conditions for maximizing the LPC
      content while suppressing acyl migration, which causes GPC formation, were as
      follows: temperature, 60 degrees C; reaction time, 3 h; water content, 10% of PC;
      and enzyme loading, 1% of PC. When the reaction was conducted with 40 g of PC
      under these conditions, the reaction products contained 83.7 mol % LPC and were
      free of GPC. LPC had a higher total unsaturated fatty acid content than original
      PC had and was mainly composed of linoleic acid (78.0 mol % of the total fatty
      acids).

PMID- 25380221
TI  - Evaluation of Celecoxib Addition to Pain Protocol After Total Hip and Knee
      Arthroplasty Stratified by Opioid Tolerance.
AB  - OBJECTIVE: This study seeks to determine the impact that celecoxib has on
      patients' postoperative opioid consumption on the basis of whether the patient is
      opioid naive or opioid tolerant for total hip and knee arthroplasty. METHODS:
      This was a retrospective study over 1.5 years that encompassed a preperiod and
      postperiod for adding celecoxib to the pain protocol. Prescriptions for opioids
      dispensed 6 months before surgery were analyzed to assess for preoperative opioid
      tolerance. Unadjusted results were presented. Primary outcome measure was change
      in milligrams of morphine per day associated with celecoxib use as per linear
      regression analysis. Secondary outcome measures included total opioid dose,
      average pain score, length of stay, and as-needed opioid doses. RESULTS: Analysis
      included 142 patients. Unadjusted results showed that opioid-naive patients had
      greater reductions in opioid dose per day with celecoxib (49.1 vs. 80.8 mg)
      compared with tolerant patients (86.6 vs. 100.1 mg). Regression results showed
      similar results, with opioid-naive patients having a 29.9 mg reduction (95%
      confidence interval, -47.9 to -12.1; P=0.009) in opioid use per day associated
      with celecoxib use versus 5.5 mg reduction (95% confidence interval, -33.6 to
      22.5; P=0.69) for opioid-tolerant group. Opioid-naive patients also had
      significant reductions in pain scores, as-needed opioid doses, and total opioid
      dose. Opioid-tolerant patients had significant reductions only in pain scores.
      CONCLUSIONS: Both opioid-tolerant and opioid-naive patients benefited from
      celecoxib therapy, although in different ways. Opioid-tolerant patients saw
      benefits other than reductions in opioid use; opioid-naive patients had similar
      benefits, but also had significant reductions in opioid use.

PMID- 25380222
TI  - Individualized Guided Internet-delivered Cognitive-Behavior Therapy for Chronic
      Pain Patients With Comorbid Depression and Anxiety: A Randomized Controlled
      Trial.
AB  - OBJECTIVES: Depression and anxiety are commonly seen in patients with chronic
      pain which affects the patient's daily life functioning. Although considerable
      attention has been devoted to explain why depression and anxiety are frequent
      comorbid with chronic pain, little empirical work has been conducted on
      interventions that target depression and anxiety and chronic pain. The present
      study was designed to test an individualized cognitive-behavioral treatment
      delivered through the internet for persons with chronic pain and emotional
      distress. MATERIALS AND METHODS: A total of 52 patients with chronic pain and
      depression were included and randomized to either treatment for 8 weeks or to a
      control group that participated in a moderated online discussion forum. RESULTS:
      Intent-to-treat analyses showed significant decreases regarding depressive
      symptoms and pain disability in the treatment group. Results on the primary
      outcomes of depression and anxiety were in favor of the treatment group.
      Reductions were also found on pain catastrophizing. DISCUSSION: One-year follow
      up showed maintenance of improvements. We conclude that an individualized guided
      internet-delivered treatment based on cognitive-behavior therapy can be effective
      for persons with chronic pain comorbid emotional distress.

PMID- 25380223
TI  - Leading a Horse to Water: Facilitating Registration and Use of a Prescription
      Drug Monitoring Program.
AB  - OBJECTIVES: Prescription Drug Monitoring Programs (PDMPs) can help inform patient
      management, coordinate care, and identify drug safety risks, abuse, or diversion.
      However, many clinicians are not registered to use these systems, and use may be
      suboptimal. We sought to describe outreach efforts in 1 state (Oregon); quantify
      uptake of system use; identify barriers; and identify potential system
      improvements. METHODS: Program reports of outreach efforts and operational
      metrics provided rates of registration and use. A statewide survey identified
      perceived barriers and potential improvements from users and nonusers of the
      system. RESULTS: Even with extensive registration efforts, <25% of clinicians and
      pharmacists acquired PDMP accounts over 2 years of operation. Rapid increases in
      registration and use in 2013 corresponded to new requirements among large
      pharmacy chains that pharmacists register for and use the PDMP. Among surveyed
      PDMP nonusers, nearly half were unaware that they could register. Among users and
      nonusers, over two thirds indicated that time constraints were a major barrier
      and over half thought that inability to delegate access was a major barrier.
      Desired improvements included linking state systems, faster entry of pharmacy
      data, and use of unique patient identifiers. Users also wanted better insurance
      coverage for mental health and addiction referrals. DISCUSSION: Increasing
      registration and use of PDMPs remains important. Clinician feedback indicates
      that program enhancements and health care system changes would facilitate using
      and responding to PDMP information. It appears premature to judge the efficacy of
      PDMPs until best practices for their use are identified and impacts are assessed.

PMID- 25380224
TI  - Relationship Between Electromyographic Signal Amplitude and Thickness Change of
      the Trunk Muscles in Patients With and Without Low Back Pain.
AB  - OBJECTIVES: To compare the relative thickness change of the transversal abdominal
      (TrA) and lumbar multifidus (LM) muscles during activation in individuals with
      and without low back pain (LBP), and to establish a relationship between surface
      electromyography (sEMG) signal amplitude and the relative thickness change of the
      corresponding muscle during clinically relevant activity, with preferential
      activation of TrA/LM. MATERIALS AND METHODS: Thirty-seven pain-free participants
      and 36 LBP patients were assessed by ultrasound for thickness changes of TrA and
      LM and by sEMG for changes of electrical activity of the same muscles. sEMG is
      done with wireless LUMBIA system. The position of the sEMG sensors and activation
      maneuvers were chosen carefully. RESULTS: Significant group effect was found for
      relative thickness change of TrA (F1,142=60.69, P<0.0001) and LM (F1,142=36.01,
      P<0.0001). We found significant correlations between relative thickness change of
      TrA and sEMG signal amplitude on both sides for LBP (r=0.46 to 0.63, P<0.05) and
      pain-free patients (r=0.43-0.47, P<0.05). The correlation between LM thickness
      change and sEMG was significant in pain-free participants for both sides (r=0.36
      to 0.38 P<0.05), and right LM in LBP participants (r=0.43, P<0.05), but not for
      LM in LBP group (r=0.16, P=0.351). DISCUSSION: US and sEMG measurements can be
      used for objective TrA/LM assessment. Correlation results suggest that the
      relative change of the muscle thickness could be used as the indicator of the
      muscle activity. Insight into the activity of TrA/LM in pain-free individuals and
      LBP patients during and after painful episodes may clarify the role of functional
      abnormalities of these muscles in LBP.

PMID- 25380225
TI  - Pressure-induced conformation transition of o-phenylene solvated in bulk
      hydrocarbons.
AB  - The conformational behavior of o-phenylene 8-mers and 10-mers solvated in a
      series of linear alkane solvents by means of classical molecular dynamics and
      first-principles calculations was studied. Irrespective of the solvent used, we
      find that at ambient pressure the molecule sits in the well-defined close-helical
      arrangement previously observed in light polar solvents. However, for pressures
      greater than 50 atm, and for tetradecane or larger solvent molecules, our
      simulations predict that o-phenylene undergoes a conformational transition to an
      uncoiled, extended geometry with a 35% longer head-to-tail distance and a much
      larger overlap between its lateral aromatic ring groups. The free energy barrier
      for the transition was studied as a function of pressure and temperature for both
      solute molecules in butane and hexadecane. Gas-phase density functional theory
      based nudged elastic band calculations on 8-mer and 10-mer o-phenylene were used
      to estimate how the pressure-induced transition energy barrier changes with
      solute length. Our results indicate that a sufficiently large solvent molecule
      size is the key factor enabling a configuration transition upon pressure changes
      and that longer solute molecules associate with higher conformation transition
      energy barriers. This suggests the possibility of designing systems in which a
      solute molecule can be selectively "activated" by a controlled conformation
      transition achieved at a predefined set of pressure and temperature conditions. 

PMID- 25380228
TI  - Servo-integrated patterned media by hybrid directed self-assembly.
AB  - A hybrid directed self-assembly approach is developed to fabricate unprecedented
      servo-integrated bit-patterned media templates, by combining sphere-forming block
      copolymers with 5 teradot/in.(2) resolution capability, nanoimprint and optical
      lithography with overlay control. Nanoimprint generates prepatterns with
      different dimensions in the data field and servo field, respectively, and optical
      lithography controls the selective self-assembly process in either field. Two
      distinct directed self-assembly techniques, low-topography graphoepitaxy and high
      topography graphoepitaxy, are elegantly integrated to create bit-patterned
      templates with flexible embedded servo information. Spinstand magnetic test at 1
      teradot/in.(2) shows a low bit error rate of 10(-2.43), indicating fully
      functioning bit-patterned media and great potential of this approach for
      fabricating future ultra-high-density magnetic storage media. 

PMID- 25380226
TI  - Musashi proteins are post-transcriptional regulators of the epithelial-luminal
      cell state.
AB  - The conserved Musashi (Msi) family of RNA binding proteins are expressed in
      stem/progenitor and cancer cells, but generally absent from differentiated cells,
      consistent with a role in cell state regulation. We found that Msi genes are
      rarely mutated but frequently overexpressed in human cancers and are associated
      with an epithelial-luminal cell state. Using ribosome profiling and RNA-seq
      analysis, we found that Msi proteins regulate translation of genes implicated in
      epithelial cell biology and epithelial-to-mesenchymal transition (EMT), and
      promote an epithelial splicing pattern. Overexpression of Msi proteins inhibited
      the translation of Jagged1, a factor required for EMT, and repressed EMT in cell
      culture and in mammary gland in vivo. Knockdown of Msis in epithelial cancer
      cells promoted loss of epithelial identity. Our results show that mammalian Msi
      proteins contribute to an epithelial gene expression program in neural and
      mammary cell types. 

PMID- 25380227
TI  - Integrated control of transporter endocytosis and recycling by the arrestin
      related protein Rod1 and the ubiquitin ligase Rsp5.
AB  - After endocytosis, membrane proteins can recycle to the cell membrane or be
      degraded in lysosomes. Cargo ubiquitylation favors their lysosomal targeting and
      can be regulated by external signals, but the mechanism is ill-defined. Here, we
      studied the post-endocytic trafficking of Jen1, a yeast monocarboxylate
      transporter, using microfluidics-assisted live-cell imaging. We show that the
      ubiquitin ligase Rsp5 and the glucose-regulated arrestin-related trafficking
      adaptors (ART) protein Rod1, involved in the glucose-induced internalization of
      Jen1, are also required for the post-endocytic sorting of Jen1 to the yeast
      lysosome. This new step takes place at the trans-Golgi network (TGN), where Rod1
      localizes dynamically upon triggering endocytosis. Indeed, transporter
      trafficking to the TGN after internalization is required for their degradation.
      Glucose removal promotes Rod1 relocalization to the cytosol and Jen1
      deubiquitylation, allowing transporter recycling when the signal is only
      transient. Therefore, nutrient availability regulates transporter fate through
      the localization of the ART/Rsp5 ubiquitylation complex at the TGN. 

PMID- 25380231
TI  - Absolute quantitative (1)h NMR spectroscopy for compound purity determination.

PMID- 25380229
TI  - Prevention of Selenite-Induced Cataratogenesis by Ginkgo biloba Extract (Egb761)
      in Wistar Rats.
AB  - OBJECTIVE: To investigate whether Ginkgo biloba extract retards selenite-induced
      cataractogenesis in Wistar rat pups. METHODS: On postpartum day eight, Group I
      rat pups (n = 12) received an intraperitoneal injection of physiological saline.
      Groups II and III rat pups (n = 12) received a subcutaneous injection of sodium
      selenite. Group III also received an intraperitoneal injection of G. biloba
      extract once daily on postpartum days 9-14. Both eyes of each pup were examined
      from postpartum day 16 up to day 30. After sacrifice, encapsulated pup lens were
      analyzed for mean activities of catalase, superoxide dismutase, glutathione
      peroxidase (GPx), glutathione S-transferase and glutathione reductase. In
      addition, the mean concentrations of reduced glutathione (GSH) and
      malondialdehyde were analyzed in samples of lens and serum. RESULTS: Dense
      lenticular opacification occurs 100% in Group II, but only minimal opacification
      occurs in three pups of Group III (25%), no opacification in 75% of Group III,
      none in Group I. Compared with Groups I and III, Group II rat showed lower
      lenticular antioxidant enzyme activity, lower level of GSH, and higher level of
      malondidehyde (mean +/- standard deviation SD, p < 0.05 respectively).
      CONCLUSIONS: The treatment with G. biloba extract is effective against oxidative
      stress - a crucial factor of cataractogenesis in rat pups, possibly by preventing
      depletion of antioxidant enzymes and by inhibiting lipid peroxidation.

PMID- 25380232
TI  - A longitudinal investigation of children internationally adopted at school age.
AB  - Most existing research on children adopted internationally has focused on those
      adopted as infants and toddlers. The current study longitudinally tracked several
      outcomes, including cognitive, behavioral, emotional, attachment, and family
      functioning, in 25 children who had been internationally adopted at school age (M
      = 7.7 years old at adoption, SD = 3.4, range = 4-15 years). We examined the
      incidence of clinically significant impairments, significant change in outcomes
      over the three study points, and variables that predicted outcomes over time.
      Clinically significant impairments in sustained attention, full-scale
      intelligence, reading, language, executive functioning, externalizing problems,
      and parenting stress were common, with language and executive functioning
      impairments present at higher levels in the current study compared with past
      research focusing on children adopted as infants and toddlers. Over the three
      study points, significant improvements across most cognitive areas and attachment
      functioning were observed, though significant worsening in executive functioning
      and internalizing problems was present. Adoptive family-specific variables, such
      as greater maternal education, smaller family size, a parenting approach that
      encouraged age-expected behaviors, home schooling, and being the sole adopted
      child in the family were associated with greater improvement across several
      cognitive outcomes. In contrast, decreased parenting stress was predicted by
      having multiple adopted children and smaller family sizes were associated with
      greater difficulties with executive functioning. Child-specific variables were
      also linked to outcomes, with girls displaying worse attachment and poorer
      cognitive performance and with less time in orphanage care resulting in greater
      adoption success. Implications for future research and clinical applications are
      discussed.

PMID- 25380233
TI  - Assessment of lumbar intervertebral disc glycosaminoglycan content by gadolinium
      enhanced MRI before and after 21-days of head-down-tilt bedrest.
AB  - During spaceflight, it has been shown that intervertebral discs (IVDs) increase
      in height, causing elongation of the spine up to several centimeters. Astronauts
      frequently report dull lower back pain that is most likely of discogenic origin
      and may result from IVD expansion. It is unknown whether disc volume solely
      increases by water influx, or if the content of glycosaminoglycans also changes
      in microgravity. Aim of this pilot study was to investigate effects of the
      spaceflight analog of bedrest on the glycosaminoglycan content of human lumbar
      IVDs. Five healthy, non-smoking, male human subjects of European descent were
      immobilized in 6 degrees  head-down-tilt bedrest for 21 days. Subjects remained
      in bed 24 h a day with at least one shoulder on the mattress. Magnetic Resonance
      Imaging (MRI) scans were taken according to the delayed gadolinium-enhanced
      magnetic resonance imaging (dGEMRIC) protocol before and after bedrest. The
      outcome measures were T1 and DeltaT1. Scans were performed before and after
      administration of the contrast agent Gd-DOTA, and differences between T1-values
      of both scans (DeltaT1) were computed. DeltaT1 is the longitudinal relaxation
      time in the tissue and inversely related to the glycosaminoglycan-content. For
      data analysis, IVDs L1/2 to L4/5 were semi-automatically segmented. Zones were
      defined and analyzed separately. Results show a highly significant decrease in
      DeltaT1 (p<0.001) after bedrest in all IVDs, and in all areas of the IVDs. The
      DeltaT1-decrease was most prominent in the nucleus pulposus and in L4/5, and was
      expressed slightly more in the posterior than anterior IVD. Unexpected negative
      DeltaT1-values were found in Pfirrmann-grade 2-discs after bedrest. Significantly
      lower T1 before contrast agent application was found after bedrest compared to
      before bedrest. According to the dGEMRIC-literature, the decrease in DeltaT1 may
      be interpreted as an increase in glycosaminoglycans in healthy IVDs during
      bedrest. This interpretation seems contradictory to previous findings in IVD
      unloading. 

PMID- 25380234
TI  - Metal-free alpha-hydroxylation of alpha-unsubstituted beta-oxoesters and beta
      oxoamides.
AB  - A direct metal-free alpha-hydroxylation of alpha-unsubstituted beta-oxoesters and
      beta-oxoamides was developed using m-chloroperbenzoic acid as the oxidant. This
      transformation enabled straightforward metal-free access to important alpha
      hydroxy-beta-dicarbonyl moieties under mild reaction conditions. Furthermore, the
      hydroxylated products were readily converted into vicinal tricarbonyl compounds,
      which are useful synthetic precursors of numerous biological targets. 

PMID- 25380235
TI  - A five-coordinate heme dioxygen adduct isolated within a metal-organic framework.
AB  - The porphyrinic metal-organic framework (MOF) PCN-224 is metalated with Fe(II) to
      yield a 4-coordinate ferrous heme-containing compound. The heme center binds O2
      at -78  degrees C to give a 5-coordinate heme-O2 complex. For the first time,
      this elusive species is structurally characterized, revealing an Fe(III) center
      coordinated to superoxide via an end-on, eta(1) linkage. Mossbauer spectroscopy
      supports the structural observations and indicates the presence of a low-spin
      electronic configuration for Fe(III). Finally, variable-temperature O2 adsorption
      data enable quantification of the Fe-O2 interaction, providing a binding enthalpy
      of -34(4) kJ/mol. This value is nearly half of that observed for comparable 6
      coordinate, imidazole-bound heme-O2 complexes, a difference that further
      illustrates the importance of axial ligands in biological heme-mediated O2
      transport and storage. These results demonstrate the ability of a MOF, by virtue
      of its rigid solid-state structure, to enable isolation and thorough
      characterization of a species that can only be observed transiently in molecular
      form. 

PMID- 25380236
TI  - Efficient quasisolid dye- and quantum-dot-sensitized solar cells using
      thiolate/disulfide redox couple and CoS counter electrode.
AB  - For the first time, a quasisolid thiolate/disulfide-based electrolyte was
      prepared using succinonitrile as a matrix. An optimized configuration of the
      quasisolid electrolyte contains 5-mercapto-1-methyltetrazole N
      tetramethylammonium/disulfide/LiClO4/N-methylbenzimidazole in the molar ratio of
      0.8:0.8:0.1:0.1. Dye-sensitized solar cells fabricated using this quasisolid
      electrolyte, together with N719 dye-sensitized photoelectrode and CoS counter
      electrode, attained power conversion efficiencies of 4.25% at 1 sun and 6.19% at
      0.1 sun illumination intensities. The optimized quasisolid electrolyte, when
      introduced to quasisolid CdS quantum-dot-sensitized solar cells, exhibited a
      power conversion efficiency of 0.94%, despite the fact that CdS absorbs only a
      small fraction of the visible light, unlike dyes. The encouraging results show
      the potential for the utilization of the quasisolid thiolate/disulfide-based
      electrolyte in sensitized solar cells.

PMID- 25380237
TI  - Role of retinoic acid and platelet-derived growth factor receptor cross talk in
      the regulation of neonatal gonocyte and embryonal carcinoma cell differentiation.
AB  - Neonatal gonocytes are direct precursors of spermatogonial stem cells, the cell
      pool that supports spermatogenesis. Although unipotent in vivo, gonocytes express
      pluripotency genes common with embryonic stem cells. Previously, we found that
      all-trans retinoic acid (RA) induced the expression of differentiation markers
      and a truncated form of platelet-derived growth factor receptor (PDGFR)beta in
      rat gonocytes, as well as in F9 mouse embryonal carcinoma cells, an embryonic
      stem cell-surrogate that expresses somatic lineage markers in response to RA. The
      present study is focused on identifying the signaling pathways involved in RA
      induced gonocyte and F9 cell differentiation. Mitogen-activated protein kinase
      kinase (MEK) 1/2 activation was required during F9 cell differentiation towards
      somatic lineage, whereas its inhibition potentiated RA-induced Stra8 expression,
      suggesting that MEK1/2 acts as a lineage specification switch in F9 cells. In
      both cell types, RA increased the expression of the spermatogonial/premeiotic
      marker Stra8, which is in line with F9 cells being at a stage before somatic
      germline lineage specification. Inhibiting PDGFR kinase activity reduced RA
      induced Stra8 expression. Interestingly, RA increased the expression of
      PDGFRalpha variant forms in both cell types. Together, these results suggest a
      potential cross talk between RA and PDGFR signaling pathways in cell
      differentiation. RA receptor-alpha inhibition partially reduced RA effects on
      Stra8 in gonocytes, indicating that RA acts in part via RA receptor-alpha. RA
      induced gonocyte differentiation was significantly reduced by inhibiting SRC (v
      src avian sarcoma [Schmidt-Ruppin A-2] viral oncogene) and JAK2/STAT5 (Janus
      kinase 2/signal transducer and activator of transcription 5) activities, implying
      that these signaling molecules play a role in gonocyte differentiation. These
      results suggest that gonocyte and F9 cell differentiation is regulated via cross
      talk between RA and PDGFRs using different downstream pathways.

PMID- 25380239
TI  - An antifungal mechanism of curcumin lies in membrane-targeted action within
      Candida albicans.
AB  - The aim of this study is to investigate the antifungal mechanism of curcumin.
      This polyphenolic compound has been used traditionally in Asia for medicinal,
      culinary, and other purposes. Although antifungal effect of curcumin has been
      reported, this is the first study for its mode of action underlying disruption of
      plasma membrane in Candida albicans. The leakage of potassium ion from the fungal
      cytosol and dissipation in membrane potential was detected by bis-(1,3
      dibutylbarbituric acid)trimethine oxonol [DiBAC4 ] staining. We also investigated
      an increase in membrane permeability in curcumin-treated C. albicans with influx
      of propidium iodide assay. Fluorescence analysis with 1,6-diphenyl-1,3,5
      hexatriene supported the membrane-targeted mechanism of action indicating
      membrane disruption. On the basis of these results, we studied the effects of
      curcumin treatment on model membrane to elucidate its antifungal mechanism. Using
      calcein leakage assays from curcumin-treated large unilamellar vesicles and giant
      unilamellar vesicles, we found that curcumin has membrane-active mechanism
      inducing leakage of intracellular component through the flappy membrane.
      Therefore, this study suggests that curcumin exerts antifungal activity via
      inducing disruption of fungal plasma membrane.

PMID- 25380240
TI  - Insecticidal activities of chiral N-trifluoroacetyl sulfilimines as potential
      ryanodine receptor modulators.
AB  - This is the first report of novel chiral N-trifluoroacetyl sulfilimines during
      research for new environmentally benign and ecologically safe novel insecticides
      with new modes of action. Four series of phthalamides containing 20 new
      structures were designed, synthesized, and evaluated against oriental armyworm
      (Pseudaletia separata Walker) and diamondback moth (Plutella xylostella (L.)) for
      their insecticidal activities. The target compounds were established by
      corresponding (1)H NMR, HRMS (or elemental analysis), X-ray diffraction analysis,
      and optical polarimetry. Introduction of chiral N-trifluoroacetyl sulfiliminyl
      moieties into the new scaffolds showed that some target compounds possessed
      impressive activities as commercial flubendiamide. These N-trifluoroacetyl
      sulfilimines exhibited the sequence of activity against oriental armyworm as (Sc,
      Ss) >= (Sc, Rs) ? (Rc, Rs) > (Rc, Ss), in which the chiral carbon influenced the
      activities stronger than sulfur. For diamondback moth, compounds If, IIa, and IIc
      exhibited even stronger activity than flubendiamide; especially If displayed a
      death rate of 100% at 10(-6) mg L(-1), much better than that of flubendiamide (0%
      at 10(-4) mg L(-1)). Comparative molecular field analysis calculation indicated
      that stereoisomers with Sc configurations containing more electronegative group
      as COCF3 are favorable to the insecticidal activity. The present work
      demonstrated that chiral N-trifluoroacetyl sulfilimines can be considered as
      potential insect ryanodine receptor modulators. From the standpoint of molecular
      design, it was concluded that the conventional second methyl group in the
      aliphatic amido side chain of dicarboxamide might not be a requisite in our
      research on novel sulfiliminyl insecticides. 

PMID- 25380241
TI  - Long-term effectiveness of bee venom acupuncture and physiotherapy in the
      treatment of adhesive capsulitis: a one-year follow-up analysis of a previous
      randomized controlled trial.
AB  - OBJECTIVE: An earlier randomized controlled trial (RCT) study showed that bee
      venom acupuncture (BVA) in combination with physiotherapy can be more effective
      in functional improvement and pain reduction in patients with adhesive capsulitis
      (AC). The objective of the current study was to examine the long-term effect of
      BVA in combination with physiotherapy on AC of the shoulder. DESIGN:
      Retrospective 1-year follow-up analysis of a previous RCT using a telephone
      interview method. SETTING: Outpatient joint center at the Gang Dong Kyung Hee
      University Hospital of Seoul, Republic of Korea. PATIENTS: A total of 192
      patients had been enrolled in the previous study, and 124 of these were excluded
      from the current study. Sixty-eight patients who had been treated with combined
      BVA and physiotherapy for AC of the shoulder for 2 months were interviewed at
      approximately 1 year after treatment by telephone. INTERVENTION: Sixty of 68
      patients were included in the follow-up analysis. Twenty received BV 1 treatment
      (1:10,000 concentration BVA plus physiotherapy), 22 received BV 2 treatment
      (1:30,000 concentration BVA plus physiotherapy), and 18 received control
      treatment (normal saline injection plus physiotherapy). OUTCOME MEASURES: The
      primary outcome measure was Shoulder Pain And Disability Index (SPADI) score.
      Secondary outcome measure was score on verbal rating scale for pain and patient
      satisfaction. RESULTS: Baseline characteristics of the groups did not
      significantly differ. SPADI scores at 1 year significantly differed between the
      BV 1 group and the control group (p=0.043). No significant differences were found
      in pain verbal rating scores after 1 year. Treatment satisfaction with therapy
      was also assessed, and the BV 1 and BV 2 groups showed significantly greater
      satisfaction compared with the control group. CONCLUSIONS: BVA combined with
      physiotherapy remains clinically effective 1 year after treatment and may help
      improve long-term quality of life in patients with AC of the shoulder.

PMID- 25380242
TI  - A comprehensive genomic approach for neuromuscular diseases gives a high
      diagnostic yield.
AB  - OBJECTIVE: Neuromuscular diseases (NMDs) are a group of >200 highly genetically
      as well as clinically heterogeneous inherited genetic disorders that affect the
      peripheral nervous and muscular systems, resulting in gross motor disability. The
      clinical and genetic heterogeneities of NMDs make disease diagnosis complicated
      and expensive, often involving multiple tests. METHODS: To expedite the molecular
      diagnosis of NMDs, we designed and validated several next generation sequencing
      (NGS)-based comprehensive gene panel tests that include complementary deletion
      and duplication testing through comparative genomic hybridization arrays. Our
      validation established the targeted gene panel test to have 100% sensitivity and
      specificity for single nucleotide variant detection. To compare the clinical
      diagnostic yields of single gene (NMD-associated) tests with the various NMD NGS
      panel tests, we analyzed data from all clinical tests performed at the Emory
      Genetics Laboratory from October 2009 through May 2014. We further compared the
      clinical utility of the targeted NGS panel test with that of exome sequencing
      (ES). RESULTS: We found that NMD comprehensive panel testing has a 3-fold greater
      diagnostic yield (46%) than single gene testing (15-19%). Sanger fill-in of low
      coverage exons, copy number variation analysis, and thorough in-house validation
      of the assay all complement panel testing and allow the detection of all types of
      causative pathogenic variants, some of which (about 18%) may be missed by ES.
      INTERPRETATION: Our results strongly indicate that for molecular diagnosis of
      heterogeneous disorders such as NMDs, targeted panel testing has the highest
      clinical yield and should therefore be the preferred first-tier approach.

PMID- 25380243
TI  - Facile palladium-catalyzed hydrocarboxylation of olefins without external CO gas.
AB  - An effective Pd-catalyzed hydrocarboxylation of olefins with phenyl formate and
      formic acid is described. A variety of carboxylic acids are obtained in good
      yields with high regioselectivities under operationally simple conditions without
      the use of toxic CO gas. 

PMID- 25380238
TI  - Expression and distribution of glucagon-like peptide-1 receptor mRNA, protein and
      binding in the male nonhuman primate (Macaca mulatta) brain.
AB  - Glucagon-like peptide-1 (GLP-1) is released from endocrine L-cells lining the gut
      in response to food ingestion. However, GLP-1 is also produced in the nucleus of
      the solitary tract, where it acts as an anorectic neurotransmitter and key
      regulator of many autonomic and neuroendocrine functions. The expression and
      projections of GLP-1-producing neurons is highly conserved between rodent and
      primate brain, although a few key differences have been identified. The GLP-1
      receptor (GLP-1R) has been mapped in the rodent brain, but no studies have
      described the distribution of GLP-1Rs in the nonhuman primate central nervous
      system. Here, we characterized the distribution of GLP-1R mRNA and protein in the
      adult macaque brain using in situ hybridization, radioligand receptor
      autoradiography, and immunohistochemistry with a primate specific GLP-1R
      antibody. Immunohistochemistry demonstrated that the GLP-1R is localized to cell
      bodies and fiber terminals in a very selective distribution throughout the brain.
      Consistent with the functional role of the GLP-1R system, we find the highest
      concentration of GLP-1R-immunoreactivity present in select hypothalamic and
      brainstem regions that regulate feeding, including the paraventricular and
      arcuate hypothalamic nuclei, as well as the area postrema, nucleus of the
      solitary tract, and dorsal motor nucleus of the vagus. Together, our data
      demonstrate that GLP-1R distribution is highly conserved between rodent and
      primate, although a few key species differences were identified, including the
      amygdala, where GLP-1R expression is much higher in primate than in rodent.

PMID- 25380244
TI  - In silico pooling of ChIP-seq control experiments.
AB  - As next generation sequencing technologies are becoming more economical, large
      scale ChIP-seq studies are enabling the investigation of the roles of
      transcription factor binding and epigenome on phenotypic variation. Studying such
      variation requires individual level ChIP-seq experiments. Standard designs for
      ChIP-seq experiments employ a paired control per ChIP-seq sample. Genomic
      coverage for control experiments is often sacrificed to increase the resources
      for ChIP samples. However, the quality of ChIP-enriched regions identifiable from
      a ChIP-seq experiment depends on the quality and the coverage of the control
      experiments. Insufficient coverage leads to loss of power in detecting
      enrichment. We investigate the effect of in silico pooling of control samples
      within multiple biological replicates, multiple treatment conditions, and
      multiple cell lines and tissues across multiple datasets with varying levels of
      genomic coverage. Our computational studies suggest guidelines for performing in
      silico pooling of control experiments. Using vast amounts of ENCODE data, we show
      that pairwise correlations between control samples originating from multiple
      biological replicates, treatments, and cell lines/tissues can be grouped into two
      classes representing whether or not in silico pooling leads to power gain in
      detecting enrichment between the ChIP and the control samples. Our findings have
      important implications for multiplexing samples. 

PMID- 25380245
TI  - Comparison of surface markers between human and rabbit mesenchymal stem cells.
AB  - This study investigated whether there are marked differences in surface markers
      between rabbit and human mesenchymal stem cells (MSCs). Murine and rabbit MSCs
      have been reported to be CD90-negative. Rat MSCs have been reported to be CD71
      negative. Our previous study also shows that rabbit MSCs are CD29-negative.
      However, human MSCs are generally considered to be CD29-, CD71-, and CD90
      positive. Therefore, the surface markers of human MSCs might differ from those of
      other species. Rabbit bone marrow MSCs were obtained that had a multi
      differentiation potential. The phenotype of these cells was studied using flow
      cytometry antibodies for 25 rabbit surface markers, namely, CD13, CD14, CD29,
      CD31, CD34, CD44, CD45, CD49d, CD49f, CD51, CD54, CD59, CD71, CD73, CD90, CD105,
      CD106, CD133, CD166, MHC I, MHC II, alpha-smooth muscle actin (alpha-SMA),
      cytokeratin, desmin, and vimentin. The phenotype of commercially available human
      MSCs was similarly studied using antibodies for human surface markers. CD14,
      CD31, CD34, CD45, CD49d, CD49f, CD51, CD54, CD71, CD106, CD133, MHC II, and
      cytokeratin were absent from both rabbit and human MSCs, while CD44, alpha-SMA,
      and vimentin were present on both cell lines. CD13, CD29, CD59, CD73, CD90,
      CD105, CD166, and MHC I were present on human MSCs, but not on rabbit MSCs.
      However, desmin was present on rabbit MSCs, but not on human MSCs. In total, the
      surface expression of nine markers differed between human and rabbit MSCs,
      whereas the surface expression of 16 markers was the same in the two cell lines. 

PMID- 25380246
TI  - Further insights into metal-DOM interaction: consideration of both fluorescent
      and non-fluorescent substances.
AB  - Information on metal binding with fluorescent substances has been widely studied.
      By contrast, information on metal binding with non-fluorescent substances remains
      lacking despite the dominance of these substances in aquatic systems. In this
      study, the metal binding properties of both fluorescent and non-fluorescent
      substances were investigated by using metal titration combined with two
      dimensional correlation spectroscopy (2D-COS) analysis. The organic matters in
      the eutrophic algae-rich lake, including natural organic matters (NOM) and algae
      induced extracellular polymeric substances (EPS), both contained fluorescent and
      non-fluorescent substances. The peaks in the one-dimensional spectra strongly
      overlapped, while 2D-COS can decompose the overlapped peaks and thus enhanced the
      spectral resolution. Moreover, 2D FTIR COS demonstrated that the binding
      susceptibility of organic ligands in both NOM and algal EPS matrices followed the
      order: 3400>1380>1650 cm-1, indicative the significant contribution of non
      fluorescent ligands in metal binding. The modified Stern-Volmer equation also
      revealed a substantial metal binding potential for the non-fluorescent substances
      (logKM: 3.57~4.92). As for the effects of organic ligands on metal binding, EPS
      was characterized with higher binding ability than NOM for both fluorescent and
      non-fluorescent ligands. Algae-induced EPS and the non-fluorescent substances in
      eutrophic algae-rich lakes should not be overlooked because of their high metal
      binding potential. 

PMID- 25380247
TI  - A motivational determinant of facial emotion recognition: regulatory focus
      affects recognition of emotions in faces.
AB  - Two studies examined an unexplored motivational determinant of facial emotion
      recognition: observer regulatory focus. It was predicted that a promotion focus
      would enhance facial emotion recognition relative to a prevention focus because
      the attentional strategies associated with promotion focus enhance performance on
      well-learned or innate tasks - such as facial emotion recognition. In Study 1, a
      promotion or a prevention focus was experimentally induced and better facial
      emotion recognition was observed in a promotion focus compared to a prevention
      focus. In Study 2, individual differences in chronic regulatory focus were
      assessed and attention allocation was measured using eye tracking during the
      facial emotion recognition task. Results indicated that the positive relation
      between a promotion focus and facial emotion recognition is mediated by shorter
      fixation duration on the face which reflects a pattern of attention allocation
      matched to the eager strategy in a promotion focus (i.e., striving to make hits).
      A prevention focus did not have an impact neither on perceptual processing nor on
      facial emotion recognition. Taken together, these findings demonstrate important
      mechanisms and consequences of observer motivational orientation for facial
      emotion recognition. 

PMID- 25380249
TI  - 3D Cultures of prostate cancer cells cultured in a novel high-throughput culture
      platform are more resistant to chemotherapeutics compared to cells cultured in
      monolayer.
AB  - Despite monolayer cultures being widely used for cancer drug development and
      testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively
      poor predictors of whether a drug will provide clinical benefit. Whilst generally
      more complicated, three dimensional (3D) culture systems often better
      recapitulate true cancer architecture and provide a more accurate drug response.
      As a step towards making 3D cancer cultures more accessible, we have developed a
      microwell platform and surface modification protocol to enable high throughput
      manufacture of 3D cancer aggregates. Herein we use this novel system to
      characterize prostate cancer cell microaggregates, including growth kinetics and
      drug sensitivity. Our results indicate that prostate cancer cells are viable in
      this system, however some non-cancerous prostate cell lines are not. This system
      allows us to consistently control for the presence or absence of an apoptotic
      core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D
      microaggregates display poor polarity. Critically the response of 3D
      microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with
      in vivo results than the equivalent 2D controls. Cumulatively, our results
      demonstrate that these prostate cancer microaggregates better recapitulate the
      morphology of prostate tumors compared to 2D and can be used for high-throughput
      drug testing. 

PMID- 25380248
TI  - A longitudinal assessment of sleep timing, circadian phase, and phase angle of
      entrainment across human adolescence.
AB  - The aim of this descriptive analysis was to examine sleep timing, circadian
      phase, and phase angle of entrainment across adolescence in a longitudinal study
      design. Ninety-four adolescents participated; 38 (21 boys) were 9-10 years
      ("younger cohort") and 56 (30 boys) were 15-16 years ("older cohort") at the
      baseline assessment. Participants completed a baseline and then follow-up
      assessments approximately every six months for 2.5 years. At each assessment,
      participants wore a wrist actigraph for at least one week at home to measure self
      selected sleep timing before salivary dim light melatonin onset (DLMO) phase - a
      marker of the circadian timing system - was measured in the laboratory. Weekday
      and weekend sleep onset and offset and weekend-weekday differences were derived
      from actigraphy. Phase angles were the time durations from DLMO to weekday sleep
      onset and offset times. Each cohort showed later sleep onset (weekend and
      weekday), later weekend sleep offset, and later DLMO with age. Weekday sleep
      offset shifted earlier with age in the younger cohort and later in the older
      cohort after age 17. Weekend-weekday sleep offset differences increased with age
      in the younger cohort and decreased in the older cohort after age 17. DLMO to
      sleep offset phase angle narrowed with age in the younger cohort and became
      broader in the older cohort. The older cohort had a wider sleep onset phase angle
      compared to the younger cohort; however, an age-related phase angle increase was
      seen in the younger cohort only. Individual differences were seen in these
      developmental trajectories. This descriptive study indicated that circadian phase
      and self-selected sleep delayed across adolescence, though school-day sleep
      offset advanced until no longer in high school, whereupon offset was later. Phase
      angle changes are described as an interaction of developmental changes in sleep
      regulation interacting with psychosocial factors (e.g., bedtime autonomy).

PMID- 25380250
TI  - Metabolic syndrome triggered by high-fructose diet favors choroidal
      neovascularization and impairs retinal light sensitivity in the rat.
AB  - Diabetic retinopathy and age-related macular degeneration are the leading causes
      of blindness in Western populations. Although it is a matter of controversy,
      large-scale population-based studies have reported increased prevalence of age
      related macular degeneration in patients with diabetes or diabetic retinopathy.
      We hypothesized that metabolic syndrome, one of the major risk factors for type 2
      diabetes, would represent a favorable environment for the development of
      choroidal neovascularization, the main complication of age-related macular
      degeneration. The fructose-fed rat was used as a model for metabolic syndrome in
      which choroidal neovascularization was induced by laser photocoagulation. Male
      Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated
      chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals
      expectedly developed significant body adiposity (+17%), liver steatosis at 3 and
      6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and
      hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained
      normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss
      of rod sensitivity to light stimulus and reduced amplitude of oscillatory
      potentials at 6 months. Fructose-fed rats developed significantly more choroidal
      neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3
      months of diet compared to animals fed the control diet. These results were
      consistent with infiltration/activation of phagocytic cells and up-regulation of
      pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data
      therefore suggested that metabolic syndrome would exacerbate the development of
      choroidal neovascularization in our experimental model. 

PMID- 25380251
TI  - Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat
      trigeminal ganglions with orofacial inflammatory pain.
AB  - Orofacial inflammatory pain is a difficult clinical problem, and the specific
      molecular mechanisms for this pain remain largely unexplained. The present study
      aimed to determine the differential expression of microRNAs (miRNAs) and disclose
      the underlying role of miR-125a-3p in orofacial inflammatory pain induced by
      complete Freund's adjuvant (CFA). Thirty-two differentially expressed miRNAs were
      first screened using a microarray chip in ipsilateral trigeminal ganglions (TGs)
      following CFA injection into the orofacial skin innervated by trigeminal nerve,
      and a portion of them, including miR-23a*, -24-2*, -26a, -92a, -125a-3p, -183 and
      -299 were subsequently selected and validated by qPCR. The target genes were
      predicted based on the miRWalk website and were further analyzed by gene ontology
      (GO). Further studies revealed miR-125a-3p expression was down-regulated, whereas
      both the expression of p38 MAPK (mitogen-activated protein kinase) alpha and CGRP
      (calcitonin gene-related peptide) were up-regulated in ipsilateral TGs at
      different time points after CFA injection compared with control. Furthermore,
      mechanistic study revealed that miR-125a-3p negatively regulates p38 alpha gene
      expression and is positively correlated with the head withdrawal threshold
      reflecting pain. Luciferase assay showed that binding of miR-125a-3p to the 3'UTR
      of p38 alpha gene suppressed the transcriptional activity, and overexpression of
      miR-125a-3p significantly inhibited the p38 alpha mRNA level in ND8/34 cells.
      Taken together, our results show that miR-125a-3p is negatively correlated with
      the development and maintenance of orofacial inflammatory pain via regulating p38
      MAPK. 

PMID- 25380253
TI  - Computational study of the thermochemistry of N2O5 and the kinetics of the
      reaction N2O5 + H2O -> 2 HNO3.
AB  - The multistructural method for torsional anharmonicity (MS-T) is employed to
      compute anharmonic conformationally averaged partition functions which then serve
      as the basis for the calculation of thermochemical parameters for N2O5 over the
      temperature range 0-3000 K, and thermal rate constants for the hydrolysis
      reaction N2O5 + H2O -> 2 HNO3 over the temperature range 180-1800 K. The M06-2X
      hybrid meta-GGA density functional paired with the MG3S basis set is used to
      compute the properties of all stationary points and the energies, gradients, and
      Hessians of nonstationary points along the reaction path, with further energy
      refinement at stationary points obtained via single-point CCSD(T)-F12a/cc-pVTZ
      F12 calculations including corrections for core-valence and scalar relativistic
      effects. The internal rotations in dinitrogen pentoxide are found to generate
      three structures (conformations) whose contributions are included in the
      partition function via the MS-T formalism, leading to a computed value for S
      degrees (298.15)(N2O5) of 353.45 J mol(-1) K(-1).This new estimate for S degrees
      (298.15)(N2O5) is used to reanalyze the equilibrium constants for the reaction
      NO3 + NO2 = N2O5 measured by Osthoff et al. [Phys. Chem. Chem. Phys. 2007, 9,
      5785-5793] to arrive at DeltafH  degrees (298.15) (N2O5) = 14.31 +/- 0.53 kJ mol(
      1)via the third law method, which compares well with our computed ab initio value
      of 13.53 +/- 0.56 kJ mol(-1). Finally, multistructural canonical variational
      transition-state theory with multidimensional tunneling (MS-CVT/MT) is used to
      study the kinetics for hydrolysis of N2O5 by a single water molecule, whose rate
      constant can be summarized by the Arrhenius expression 9.51 * 10(-17) (T/298
      K)(3.354) e(-7900K/T) cm3 molecule(-1) s(-1) over the temperature range 180-1800
      K.

PMID- 25380252
TI  - Determination of morphological, biometric and biochemical susceptibilities in
      healthy Eurasier dogs with suspected inherited glaucoma.
AB  - In both humans and dogs, the primary risk factor for glaucoma is high intraocular
      pressure (IOP), which may be caused by iridocorneal angle (ICA) abnormalities.
      Oxidative stress has also been implicated in retinal ganglion cell damage
      associated with glaucoma. A suspected inherited form of glaucoma was recently
      identified in Eurasier dogs (EDs), a breed for which pedigrees are readily
      available. Because of difficulties in assessing ICA morphology in dogs with
      advanced glaucoma, we selected a cohort of apparently healthy dogsfor the
      investigation of ICA morphological status, IOP and plasma concentrations of
      oxidative stress biomarkers. We aimed to establish correlations between these
      factors, to identify predictive markers of glaucoma in this dog breed. A cohort
      of 28 subjects, volunteered for inclusion by their owners, was selected by
      veterinary surgeons. These dogs were assigned to four groups: young males, young
      females (1-3 years old), adult males and adult females (4-8 years old). Ocular
      examination included ophthalmoscopy, tonometry, gonioscopy, biometry and
      ultrasound biomicroscopy (UBM), and the evaluation of oxidative stress biomarkers
      consisting of measurements of plasma glutathione peroxidase (GP) activity and
      taurine and metabolic precursor (methionine and cysteine) concentrations in
      plasma. The prevalence of pectinate ligament abnormalities was significantly
      higher in adult EDs than in young dogs. Moreover, in adult females, high IOP was
      significantly correlated with a short axial globe length, and a particularly
      large distance between Schwalbe's line and the anterior lens capsule. GP activity
      levels were significantly lower in EDs than in a randomized control group of
      dogs, and plasma taurine concentrations were higher. Hence, ICA abnormalities
      were associated with weaker antioxidant defenses in EDs, potentially counteracted
      by higher plasma taurine concentrations. This study suggests that EDs may
      constitute an appropriate canine model for the development of glaucoma. This
      cohort will be used as a sentinel for longitudinal monitoring. 

PMID- 25380254
TI  - Volume conductor model of transcutaneous electrical stimulation with kilohertz
      signals.
AB  - OBJECTIVE: Incorporating high-frequency components in transcutaneous electrical
      stimulation (TES) waveforms may make it possible to stimulate deeper nerve fibers
      since the impedance of tissue declines with increasing frequency. However, the
      mechanisms of high-frequency TES remain largely unexplored. We investigated the
      properties of TES with frequencies beyond those typically used in neural
      stimulation. APPROACH: We implemented a multilayer volume conductor model
      including dispersion and capacitive effects, coupled to a cable model of a nerve
      fiber. We simulated voltage- and current-controlled transcutaneous stimulation,
      and quantified the effects of frequency on the distribution of potentials and
      fiber excitation. We also quantified the effects of a novel transdermal amplitude
      modulated signal (TAMS) consisting of a non-zero offset sinusoidal carrier
      modulated by a square-pulse train. MAIN RESULTS: The model revealed that high
      frequency signals generated larger potentials at depth than did low frequencies,
      but this did not translate into lower stimulation thresholds. Both TAMS and
      conventional rectangular pulses activated more superficial fibers in addition to
      the deeper, target fibers, and at no frequency did we observe an inversion of the
      strength-distance relationship. Current regulated stimulation was more strongly
      influenced by fiber depth, whereas voltage regulated stimulation was more
      strongly influenced by skin thickness. Finally, our model reproduced the
      threshold-frequency relationship of experimentally measured motor thresholds.
      SIGNIFICANCE: The model may be used for prediction of motor thresholds in TES,
      and contributes to the understanding of high-frequency TES.

PMID- 25380255
TI  - [A tribute to Francois Gremy].

PMID- 25380256
TI  - [National health strategy: mixed reception of the bill].

PMID- 25380257
TI  - [School bathrooms: children's perceptions and prevalence of gastrointestinal and
      urinary disorders, a survey in 3 secondary schools near Saint-Etienne].
AB  - INTRODUCTION: Irregular use of toilets can contribute to urinary and
      gastrointestinal disorders. The aim of this study was to assess the prevalence of
      gastrointestinal and urinary symptoms among a secondary school teenage population
      and to evaluate their perception and use of school toilets. METHODS: 791
      adolescents aged 12 to 16 filled in an anonymous questionnaire, which was
      administered in three secondary schools near Saint-Etienne, France. RESULTS: 22%
      reported abdominal pain at least once a week during the past two months and 26%
      experienced abdominal pain about once every month. 9% of schoolchildren suffered
      from urinary incontinence at least once during the two months before the study:
      4% of boys and 13% of girls. Children had a negative perception of school
      toilets: 62% didn't feel safe and 54% of boys reported a lack of privacy. 34% of
      students avoided school toilets: 21% never used them to urinate and 85% never
      used them to defecate. 28% of children acknowledged they had experienced
      abdominal pain because they couldn't use school toilets and 29% said that they
      had experienced poor concentration as a result of their pain. DISCUSSION:
      Abdominal pain and urinary disorders are common among secondary schoolchildren.
      Stool and urine withholding behaviours are be widespread and affect students'
      concentration while at school.

PMID- 25380258
TI  - [Creation of a consumer representatives committee in a multidisciplinary primary
      health care center. Findings, limitations and prospects].
AB  - INTRODUCTION: The St Claude multidisciplinary health centre in Besancon
      encouraged the creation of a consumer representatives committee to promote health
      democracy in primary health care. This project was developed with the help of a
      local consumers association. This study evaluated the perception and expectations
      of these fifteen health users/citizens. METHODS: A qualitative study based on
      individual semistructured interviews was carried out before initiation of the
      project. RESULTS: The results highlight the motivation and sense of initiative of
      the participants in this innovative project, who wish to discuss a wide range of
      topics. These topics were compared to the health centre's health project. Four
      common themes emerged: maintenance at home for the elderly, management of urgent
      consultations in the health centfre, prevention and information. These themes
      were used to guide the formation of this consumer group. The limitations defined
      by the consumers were also taken into account to ensure durability of the
      project. This study identified several markers: the original modality of
      identification of representatives, the themes shared with professionals, the
      proposed method of structuring activities. DISCUSSION: These preliminary
      observations and orientations could be used by other organizations to facilitate
      the creation of a group of consumer representatives.

PMID- 25380259
TI  - [Evaluation of a workplace health promotion program].
AB  - OBJECTIVE: Some studies suggest that a workplace prevention programme could
      reduce health inequalities related to education level and improve the health
      status of the employees. The objective of the study was to demonstrate the
      advantages for a company to implement a health prevention programme in the
      workplace in order to: 1-improve health literacy 2 - change health-related
      behaviours 3-improve the company image. METHODS: A "before - after" methodology
      was used in a population of 2153 employees of three companies. Three areas of
      prevention were considered: nutrition, physical activity and prevention of back
      pain. The successive steps of the EBS programme included general communication,
      group workshops and individual coaching. Data collection was carried out using
      anonymous questionnaires sent by e-mail. A global assessment was performed based
      on the companies' pooled data, with separate analysis according to the steps of
      the programme. RESULTS: The programme mobilized employees with participation
      rates ranging from 25% to 45.5%. After completion of the full programme, 77.5% of
      respondents reported an improvement of their health knowledge versus 50.3% of
      those who only received general communication. Behavioural modification was
      observed, especially in the fields of nutrition and back pain.. EBS can be
      considered to be a vector of the company image for almost 7 out of 10 employees.
      CONCLUSION: A health prevention education programme provided by the company in
      the workplace mobilizes employees and contributes to improvement of health
      knowledge and behaviour change. All approaches tested were important and
      applicable to various types of companies or workers.

PMID- 25380260
TI  - [Health promotion: a relevant concept for a management and organizational
      dynamics tool in the restructuring of a geriatric hospital].
AB  - INTRODUCTION: The financial difficulties encountered by Martinique hospitals has
      led to restructuring of the territory's medical project with the merger of three
      healthcare facilities. These new constraints impacting the work environment with
      organizational consequences in services. METHODS: A management experiment was
      attempted in a geriatric day care hospital based on the use of health promotion
      concepts. After an overview of the unit's activity based on the perceptions of
      staff, patients and private physicians, a one-day research-action structural
      seminar was organized. RESULTS: Group dynamics, unit functioning, shared values,
      success factors, and improvement strategies were discussed. This seminar resulted
      in the development of a business model based on five values (respect,
      professionalism, cohesion, empathy, communication). Three operational working
      groups were established to implement the conclusions of the seminar in the unit.
      DISCUSSION: This experiment focused on an alternative approach to the management
      of small health care services by the use of health promotion.

PMID- 25380261
TI  - [Logic model of the Franche-Comte Regional Health Project: advantages and
      limitations for the evaluation process].
AB  - The French "Hospitals, patients, health and territories" law of July 2009 created
      the Regional Health Project (PRS) to support regional health policy, and requires
      evaluation of these projects. The construction of these projects, which includes
      prevention planning, care planning, and medical and social welfare planning,
      presents an unprecedented complexity in France, where evaluation programmes are
      still in their infancy. To support future evaluations, the Franche-Comte Regional
      Health Agency (ARS FC), assisted by the expertise of EFECT Consultants, decided
      to reconstruct the PRS logic model. This article analyzes the advantages and
      limitations of this approach. The resulting logic model allows visualization of
      the strategy adopted to achieve the Franche-Comte PRS ambitions and expected
      results. The model highlights four main aspects of structural change to the
      health system, often poorly visible in PRS presentation documents. This model
      also establishes links with the usual public policy evaluation issues and
      facilitates their prioritization. This approach also provides a better
      understanding of the importance of analysis of the programme construction in
      order to be effective rather than direct analysis of the effects, which
      constitutes the natural tendency of current practice. The main controversial
      limit concerns the retrospective design of the PRS framework, both in terms of
      the reliability of interpretation and adoption by actors not directly involved in
      this initiative. 

PMID- 25380262
TI  - [Reviewing the shared strategy health bill: further measures to meet the
      structural challenges of the health system].
AB  - This article reviews the draft health bill entitled "Federate health
      professionals around a shared strategy", currently submitted for consultation in
      the context of the national health strategy in France. This bill comprises
      innovative measures for prevention and health care in France. In particular, it
      is designed to develop, strengthen and structure the prevention sector,
      especially in children and young people. It is also designed to organize health
      care trajectories and acquire the necessary tools to promote their development.
      However, the bill sometimes presents limited ambitions in terms of objectives and
      means. In particular, the project comprises almost none of the necessary actions
      on the social determinants of health. Overall, the orientations of this bill
      represent a first major step towards a health policy in France beyond the field
      of health care. However, we must remain vigilant concerning application of these
      orientations in the process of elaboration of the bill and its related
      regulations, and implementation of the national health strategy.

PMID- 25380263
TI  - [Oral hygiene of children and adolescents participating in the dental examination
      program].
AB  - OBJECTIVE: This study was designed to analyse the dental care needs of young
      people aged 6, 9, 12, 15 and 18 years based on dental examination, assess their
      compliance with the dental care programme and improvement of their dental status
      during the nine months following the dental examination programme, in 2007 and
      2010. METHODS: Comparative study of two random samples of young people derived
      from twenty representative funds of the general national health insurance scheme:
      first sample of 24,151 young people in whom a dental examination was performed
      between 1st May and 31 July 2007, and a second sample of 24,768 young people in
      whom a dental examination was performed during the same period in 2010. RESULTS:
      The proportion of young people aged 9, 12, 15 and 18 years not requiring dental
      care and free of caries increased significantly between 2007 and 2010, in the
      context of the dental examination programme, and the DMF index (number of
      decayed, missing and filled teeth) decreased for all ages. Regardless of age, the
      proportion of children requiring dental care and who completed this care
      following the dental examination programme was not significantly different
      between the two years. The proportion of 15-year-olds and 18-year-olds requiring
      dental care, but who failed to complete dental care decreased significantly
      between 2007 and 2010. Regardless of age, nine months after the dental
      examination programme, the caries index declined significantly in 2007 and 2010.
      CONCLUSION: The dental status of young people with caries who participated in the
      dental examination programme globally improved with generally good compliance
      with their dental care programme. The current challenge is to include populations
      with more severe caries in this programme.

PMID- 25380264
TI  - [Management of sexually transmitted infections by private pharmacies in Hanoi].
AB  - AIM: This cross-sectional study comprising quantitative and qualitative analysis
      of clinical practices was designed to evaluate the quality and relevance of
      management of sexually transmitted infections (STI) based on a syndrome approach
      by private pharmacies in Hanoi in 2010 compared to a similar study conducted in
      2000. METHODS: One investigator played the role of a customer presenting signs of
      STI. He visited 60 randomly selected private pharmacies in Hanoi and noted the
      treatments, questions and advice provided by pharmacists. RESULTS: The results
      show that pharmacists proposed a treatment for 87% of cases of urethral discharge
      and 30% of cases of genital ulcers. The patient was not asked any questions in
      55% of cases. None of the prescriptions complied with national guidelines. Only
      8.3% of pharmacists/shop assistants asked the "patient" questions concerning the
      spouse/partner and 20% provided advice (the use of condoms in 26.6% of cases and
      a screening test for HIV in only one case). Pharmacists/shop assistants
      recommended consulting a doctor in only 43.3% of cases or a specialized STI
      clinic in only 16.7% of cases. CONCLUSION: The behaviour of private
      pharmacists/shop assistants in Hanoi have not changed over the last ten years
      (2000-2010). They readily treat STI inappropriately and provide little advice
      concerning prevention, screening and treatment. In the age of the HIV pandemic
      and microbial resistance to antibiotics, patients with STI should be advised to
      seek management by competent public services.

PMID- 25380265
TI  - [Patient satisfaction survey and the place of users in the Oran university
      hospital quality project].
AB  - AIM: Quality of care is a strategic priority of any management approach in order
      to meet users' expectations of health care systems. This study tried to define
      the role of patient satisfaction surveys and the place of user in the quality of
      care project. METHODS: The results of patient satisfaction surveys conducted
      between 2010 and 2012 and the draft quality of care project were analysed.
      RESULTS: Patient satisfaction surveys from 2010 to 2012 focused on logistic
      shortcomings. No comment was formulated about health care. Comments and
      suggestions did not provide any contribution in terms of patient involvement in
      the health care process. CONCLUSION: The multiple perspectives of quality of care
      include clinical care and other social objectives of respect for the individual
      and attention to the patient. User satisfaction as assessed by patient
      satisfaction surveys or patients' experiences only reflect the health
      professionals' representation. However, the objective is to measure what the user
      perceives and feels and his/her representation of the attention provided. These
      approaches, conducted outside of the quality of care strategic plan, only provide
      a basis for actions with limited or no effectiveness.

PMID- 25380266
TI  - [Determinants of strategic management of a health center].
AB  - AIM: The article highlights the value of a strategic approach for the development
      of a primary care health centre. METHODS: The method is adapted from corporate
      strategy: (i) analysis of the situation of the health centre and the obstacles to
      its development. (ii) selection of relations on which the strategy can be
      developed. (iii) elaboration of a system of interventions to create a cumulative
      development process. (iv) Illustration of the method by application to a case.
      RESULTS: The example illustrates the principles and method and highlights the
      importance of interpretations and choices in elaboration of a strategy, which is
      therefore always a unique construction. CONCLUSION: The strategic approach
      provides a framework that (i) provides a subject of discussion and negotiation
      between members of the health centre, (ii) strengthens the consistency of
      structural decisions, (iii) helps the health centre to overcome obstacles and
      initiate a development process.

PMID- 25380267
TI  - [Improving health care practices and organization: methodology for intervention
      studies].
AB  - Interventions designed to improve professional practices and healthcare
      organization are regularly implemented in all health systems. Their effectiveness
      on quality of care should be properly evaluated prior to their widespread
      implementation. Intervention studies can be conducted for this purpose according
      to a rigorous methodology in order to provide results with a good level of
      evidence. This article describes the main phases of an intervention study,
      including definition of the intervention, choice of study design, outcomes
      assessment, and writing of the report. It also addresses methodological issues of
      intervention studies designed to improve quality of care, such as cluster
      randomization or the use of quasi-experimental designs. One of the specific
      features of these studies is that professionals are the targets, while patients
      are the beneficiaries of the intervention. A good knowledge of the specific
      features of studies designed to improve quality of care is essential to conduct
      research, or to evaluate the quality of the evidence from published studies. 

PMID- 25380268
TI  - [Governance of HIV/AIDS organizations in Bobo-Dioulasso (Burkina Faso)].
AB  - INTRODUCTION: Although HIV/AIDS organizations continue to play a major role in
      the fight against pandemic HIV infections, they are still faced with enormous
      governance challenges that impair their operations / interventions and their
      sustainability. The objective of this study was to develop an inventory of the
      quality of governance within HIV/AIDS organizations in Bobo-Dioulasso. METHODS:
      This qualitative research was conducted in 40 organizations from Bobo-Dioulasso.
      Qualitative data were collected over a 45-day period using an interview guide.
      Thematic analysis of the data was performed and the results were reported.
      RESULTS: Although all 40 organizations had established good governance
      mechanisms, only fifteen complied with the major rules of democratic functioning
      and the roles of the various bodies. The majority of these organizations (29/40)
      ignored many democratic rules. The number of members required for the Executive
      Board was not met in 29/40 organizations resulting in monopolization of decision
      making by a handful of people. Technical and financial reports were not
      published, resulting in limited access to information on the organization's
      activities. Gender equality also constituted a weakness. DISCUSSION: Application
      of good governance principles was limited in these organizations. Organization
      members, leaders and technical and financial partners must reinforce good
      governance efforts in order to improve good governance in these organizations.

PMID- 25380269
TI  - [Knowledge, attitudes and practices of emergency contraception among female
      students at Parakou University (Benin)].
AB  - OBJECTIVE: This study was designed to assess emergency contraception knowledge,
      attitude and practices among female students at Parakou University. METHODS: A
      descriptive cross-sectional survey was conducted on 570 female students recruited
      after cluster sampling in the various university departments. A predefined
      questionnaire was used to interview students after they consented to participate
      in the survey. The data collected were analysed by Epi Info software and
      variables were compared by Chi-square test with a limit of significance of 5%.
      RESULTS: More than half of the students (51%) were familiar with the emergency
      contraception method and had been informed by friends and the media. Only 18% of
      them had already used this method at least once following unprotected sexual
      intercourse. Most of them were under the age of 24 and reported having irregular
      sexual partners. CONCLUSION: Students were familiar with and had easy access to
      the method. However, repeated use of this method highlights the need for better
      information of these students concerning classical methods of contraception. An
      awareness campaign should be conducted on the campus in order to reduce the
      currently high rate of non-medical clandestine abortion.

PMID- 25380270
TI  - [Knowledge, attitudes and practices of household heads regarding rabies in the
      Abobo district (Abidjan, Cote d'Ivoire) in 2008].
AB  - INTRODUCTION: In order to investigate the factors predisposing to human rabies in
      Abobo, we conducted a study to assess the knowledge, attitudes and practices of
      household heads in this district. MATERIALS AND METHODS: This cross-sectional
      study was conducted from 13 September to 13 December 2008 and consisted of
      interviewing, by means of a questionnaire, household heads or their
      representatives at home. We randomly selected 53 households in each sub-district,
      with a total of 702 households for the 13 sub-districts. Informed consent was
      obtained from each participant prior to the interview. Data were analysed using
      Epi-Info 2000. RESULTS: Of the total of 152 households, 22% had a pet; 109
      (71.7%) households had a dog, that was not vaccinated in 38% of cases.
      Furthermore, 577 (82.19%) of household heads knew about rabies and school was the
      source of information for 511 households (88.6%). Five hundred fifty five
      household heads (96.18%) did not know that the wound should be washed with soap
      and water immediately after exposure and 118 household heads (20.45%) reported
      that nothing should be done after a bite. After exposure, only 30.70% of
      household heads would attend a health centre 50 kilometres from home. CONCLUSION:
      This study shows a good level of knowledge of household heads concerning rabies.
      However, harmful health practices persist. Public awareness of rabies therefore
      needs to be reinforced.

PMID- 25380271
TI  - [Socioeconomic factors influencing exclusive breastfeeding among primiparous
      women in Abidjan (Ivory Coast)].
AB  - OBJECTIVE: To ensure complete adhesion of primiparous women with exclusive
      breastfeeding, we need to understand the factors influencing this practice. The
      objective of this study was to determine the socioeconomic factors related to
      exclusive breastfeeding of infants less than six months old born to primiparous
      mothers. METHODS: This cross-sectional descriptive and analytical study was
      conducted over a two-month period from 4 June to 6 August 2012 in three health
      facilities in the city of Abidjan. A total of 188 primiparous women were surveyed
      by a direct face-to-face questionnaire-based interview technique. RESULTS: The
      mean age of primiparous women was 26.56 +/- 5.05 years. The majority (76.60%)
      were in a couple relationship and 40.43% had completed higher education. 36.17%
      of women were working, while 23.94% were students. Only 33.51% of women performed
      exclusive breastfeeding. Exclusive breastfeeding rates decreased progressively
      with increasing age of the infant, from 46.67% at the age of one month to 16.67%
      at the age of six months. Factors associated with failure to perform exclusive
      breastfeeding were marriage, working in the public or private sector, delivery in
      a private health facility, delivery by caesarean section, living in Cocody, and
      lack of knowledge concerning exclusive breastfeeding. CONCLUSION: It is essential
      to take socio-economic factors into account when developing strategies designed
      to increase exclusive breastfeeding rates and maintenance of exclusive
      breastfeeding until the age of six months among primiparous women in Abidjan.

PMID- 25380273
TI  - Response of Daphnia's antioxidant system to spatial heterogeneity in
      Cyanobacteria concentrations in a lowland reservoir.
AB  - Many species and clones of Daphnia inhabit ecosystems with permanent algal
      blooms, and they can develop tolerance to cyanobacterial toxins. In the current
      study, we examined the spatial differences in the response of Daphnia longispina
      to the toxic Microcystis aeruginosa in a lowland eutrophic dam reservoir between
      June (before blooms) and September (during blooms). The reservoir showed a
      distinct spatial pattern in cyanobacteria abundance resulting from the wind
      direction: the station closest to the dam was characterised by persistently high
      Microcystis biomass, whereas the upstream stations had a significantly lower
      biomass of Microcystis. Microcystin concentrations were closely correlated with
      the cyanobacteria abundance (r = 0.93). The density of daphniids did not differ
      among the stations. The main objective of this study was to investigate how the
      distribution of toxic Microcystis blooms affects the antioxidant system of
      Daphnia. We examined catalase (CAT) activity, the level of the low molecular
      weight antioxidant glutathione (GSH), glutathione S-transferase (GST) activity
      and oxidative stress parameters, such as lipid peroxidation (LPO). We found that
      the higher the abundance (and toxicity) of the cyanobacteria, the lower the
      values of the antioxidant parameters. The CAT activity and LPO level were always
      significantly lower at the station with the highest M. aeruginosa biomass, which
      indicated the low oxidative stress of D. longispina at the site with the
      potentially high toxic thread. However, the low concentration of GSH and the
      highest activity of GST indicated the occurrence of detoxification processes at
      this site. These results demonstrate that daphniids that have coexisted with a
      high biomass of toxic cyanobacteria have effective mechanisms that protect them
      against the toxic effects of microcystins. We also conclude that Daphnia's
      resistance capacity to Microcystis toxins may differ within an ecosystem,
      depending on the bloom's spatial distribution. 

PMID- 25380274
TI  - A cross-sectional study of equol producer status and self-reported vasomotor
      symptoms.
AB  - OBJECTIVE: This study aims to evaluate the associations of vasomotor symptom
      (VMS) frequency, bother, and severity with equol producer status and dietary
      daidzein intake. METHODS: This is an observational study. This study included
      women aged 45 to 55 years, in postmenopause or in the menopausal transition, who
      had soy food intake of three or more servings per week. Exclusion criteria
      included severe concurrent disease, pregnancy or planned pregnancy, and current
      use of oral or transdermal hormones or selective estrogen receptor modulators.
      After screening, 375 participants completed a 3-day VMS diary and a 24-hour urine
      collection. Women with a urine daidzein or genistein concentration of 100 ng/mL
      or higher were included. We evaluated the association of VMS--dichotomized as
      lower than or equal to versus higher than the mean number of VMS per day (<2.33,
      >= 2.33)--with quartiles of daidzein intake. RESULTS: Overall, 129 (35%) of 365
      women were equol producers. The mean (SD) urinary equol excretion was 0.67 (1.57)
      mg/day (50th percentile, 0 mg/d; 95th percentile, 4.12 mg/d). Among equol
      producers, the mean (SD) urinary equol excretion was 1.91 (2.15) mg/day (50th
      percentile, 1.09 mg/d; 95th percentile, 6.27 mg/d). Among equol producers,
      compared with those in the lowest quartile of dietary daidzein intake (mean, 4.9
      mg/d), those in the highest quartile (mean, 28.5 mg/d) were 76% less likely to
      have VMS higher than the mean number of VMS (odds ratio, 0.24; 95% CI, 0.07-0.83;
      trend test across all daidzein levels, P = 0.06). Among equol nonproducers, there
      were no associations between daidzein intake and VMS frequency. There were no
      differences in VMS bother or severity among equol producers or nonproducers by
      dietary daidzein level. CONCLUSIONS: Among equol producers, higher equol
      availability attributable to higher soy consumption contributes to decreased VMS.

PMID- 25380275
TI  - Methods and baseline cardiovascular data from the Early versus Late Intervention
      Trial with Estradiol testing the menopausal hormone timing hypothesis.
AB  - OBJECTIVE: This study aims to present methods and baseline data from the Early
      versus Late Intervention Trial with Estradiol (ELITE), the only clinical trial
      designed to specifically test the timing hypothesis of postmenopausal hormone
      therapy (HT). The timing hypothesis posits that HT effects depend on the temporal
      initiation of HT relative to time since menopause. METHODS: ELITE is a
      randomized, double-blind, placebo-controlled trial with a 2 * 2 factorial design.
      Six hundred forty-three healthy postmenopausal women without cardiovascular
      disease were randomized to oral estradiol or placebo for up to 6 to 7 years
      according to time since menopause (<6 or >=10 y). Carotid artery intima-media
      thickness (CIMT) and cardiac computed tomography were conducted to determine HT
      effects on subclinical atherosclerosis across menopause strata. RESULTS:
      Participants in the early and late postmenopausal strata were well-separated by
      mean age (55.4 vs 65.4 y) and median time since menopause (3.5 vs 14.3 y).
      Expected risk factors (age, blood pressure, and body mass index) were associated
      with CIMT at baseline in both strata. In the early postmenopausal group, but not
      in the late postmenopausal group, we observed significant associations between
      CIMT and factors that may play a role in the responsiveness of atherosclerosis
      progression according to timing of HT initiation. These include low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, sex hormone
      binding globulin, and serum total estradiol. CONCLUSIONS: The ELITE randomized
      controlled trial is timely and unique. Baseline data indicate that ELITE is well
      positioned to test the HT timing hypothesis in relation to atherosclerosis
      progression and coronary artery disease.

PMID- 25380276
TI  - Disability and multimorbidity in women older than 50 years: a population-based
      household survey.
AB  - OBJECTIVE: This study aims to evaluate the prevalence of disability and
      associated factors in Brazilian women older than 50 years. METHODS: We conducted
      a cross-sectional study (in the form of a population survey) of 622 women older
      than 50 years and residing in Campinas, Brazil. Disability was assessed through a
      questionnaire with seven items and defined as "being completely unable to perform
      any of them." Independent variables included self-perception of health,
      sociodemographic data, health-related habits, and morbidities. Statistical
      analysis was carried out by chi(2) test and Poisson regression. RESULTS: The mean
      age of women was 64.1 years, and the prevalence of disability was 43.4%. Age
      (prevalence ratio [PR], 1.02; 95% CI, 1.01-1.03), fear of falling (PR, 1.59; 95%
      CI, 1.17-2.16), higher body mass index (PR, 1.03; 95% CI, 1.01-1.05), personal
      history of myocardial infarction (PR, 1.36; 95% CI, 1.06-1.76), smoking more than
      15 cigarettes per day (PR, 1.34; 95% CI, 1.04-1.72), hospitalization in the past
      year (PR, 1.29; 95% CI, 1.03-1.62), multimorbidity (PR, 1.43; 95% CI, 1.02-2.02),
      and use of any medication prescribed by a doctor (PR, 1.57; 95% CI, 1.02-2.41)
      were associated with a higher prevalence of disability. Self-perception of health
      as good/very good (PR, 0.67; 95% CI, 0.52-0.86), use of alternative medications
      (PR, 0.54; 95% CI, 0.33-0.90), and more years of schooling (PR, 0.65; 95% CI,
      0.45-0.93) were associated with a lower prevalence of disability. CONCLUSIONS:
      The results improve our understanding of the factors associated with disability
      in Brazilian women and may help identify those who need multidisciplinary support
      to reduce effects on quality of life.

PMID- 25380277
TI  - The prevalence and correlates of lifetime psychiatric disorders and trauma
      exposures in urban and rural settings: results from the national comorbidity
      survey replication (NCS-R).
AB  - INTRODUCTION: Distinctions between rural and urban environments produce different
      frequencies of traumatic exposures and psychiatric disorders. We examine the
      prevalence of psychiatric disorders and frequency of trauma exposures by position
      on the rural-urban continuum. METHODS: The National Comorbidity Survey
      Replication (NCS-R) was used to evaluate psychiatric disorders among a nationally
      representative sample of the U.S. population. Rurality was designated using the
      Department of Agriculture's 2003 rural-urban continuum codes (RUCC), which
      differentiate counties into levels of rurality by population density and
      adjacency to metropolitan areas. Lifetime psychiatric disorders included post
      traumatic stress disorder (PTSD), anxiety disorders, major depressive disorder,
      mood disorders, impulse-control disorders, and substance abuse. Trauma exposures
      were classified as war-related, accident-related, disaster-related, interpersonal
      or other. Weighted logistic regression models examined the odds of psychiatric
      disorders and trauma exposures by position on the rural-urban continuum, adjusted
      for relevant covariates. RESULTS: 75% of participants were metropolitan, 12.2%
      were suburban, and 12.8% were from rural counties. The most common disorder
      reported was any anxiety disorder (38.5%). Drug abuse was more common among
      metropolitan (8.7%, p = 0.018), compared to nonmetropolitan (5.1% suburban, 6.1%
      rural) participants. A one-category increase in rurality was associated with
      decreased odds for war-related trauma (aOR = 0.86, 95%CI 0.78-0.95). Rurality was
      not associated with risk for any other lifetime psychiatric disorders or trauma
      exposure. DISCUSSION/CONCLUSIONS: Contrary to the expectation of some rural
      primary care providers, the frequencies of most psychiatric disorders and trauma
      exposures are similar across the rural-urban continuum, reinforcing calls to
      improve mental healthcare access in resource-poor rural communities.

PMID- 25380278
TI  - Weak gelation of hydrophobic guar by albumin in simulated human tear solutions.
AB  - This initial study shows that hydrophobic modification of guar polymers used in
      eye drops forms weak gels with human serum albumin (HSA), suggesting that
      modified guar may offer advantages for treatment of dry eye diseases that lead to
      elevated HSA concentrations in tears. Specifically, hydroxypropyl guar samples
      were oxidized and derivatized with linear alkyl amines to give a series of
      modified guar polymers (MGuar) bearing hydroxypropyl, N-alkylamide, and carboxyl
      moieties. MGuar interactions with lysozyme and HSA were measured by binding and
      rheological methods as functions of the alkyl chain length and the extent of
      hydrophobic modification. HSA binds MGuar, giving weak gels, whereas lysozyme
      shows little tendency to bind MGuar or to interfere with HSA binding. Six mole
      percent substitution of decyl hydrophobes gave the strongest gels in the presence
      of HSA. 

PMID- 25380279
TI  - Crystallographically driven magnetic behaviour of arrays of monocrystalline Co
      nanowires.
AB  - Cobalt nanowires, 40 nm in diameter and several micrometers long, have been grown
      by controlled electrodeposition into ordered anodic alumina templates. The hcp
      crystal symmetry is tuned by a suitable choice of the electrolyte pH (between 3.5
      and 6.0) during growth. Systematic high resolution transmission electron
      microscopy imaging and analysis of the electron diffraction patterns reveals a
      dependence of crystal orientation from electrolyte pH. The tailored modification
      of the crystalline signature results in the reorientation of the
      magnetocrystalline anisotropy and increasing experimental coercivity and
      squareness with decreasing polar angle of the 'c' growth axis. Micromagnetic
      modeling of the demagnetization process and its angular dependence is in
      agreement with the experiment and allows us to establish the change in the
      character of the magnetization reversal: from quasi-curling to vortex domain wall
      propagation modes when the crystal 'c' axis tilts more than 75 degrees  in
      respect to the nanowire axis. 

PMID- 25380280
TI  - Phase aggregation and morphology effects on nanocarbon optoelectronics.
AB  - Controllable morphology and interfacial interactions within bulk heterojunction
      nanostructures show significant effects on optoelectronic device applications. In
      this study, a nanocarbon heterojunction, consisting of single-walled carbon
      nanotubes (s-SWCNTs) and fullerene derivatives, is reported by
      assembling/blending its structures through solution-based processes. A uniform
      and dense graphene oxide hole transport layer is used to facilitate the
      photoconversion at a near infrared (NIR) wavelength. Effective interfacial
      interaction between the s-SWCNTs and fullerene is suggested by the redshifted
      photoabsorption and nanoscale/micron-scale fluorescence, which is associated with
      self-assembled nanocarbon morphology. 

PMID- 25380281
TI  - High-performance countercurrent chromatography separation of Peucedanum cervaria
      fruit extract for the isolation of rare coumarin derivatives.
AB  - For the first time, rare major and minor compounds from fruits of Peucedanum
      cervaria were isolated. High-performance countercurrent chromatography with two
      different solvent systems, heptane/ethyl acetate/methanol/water (3:2:3:2 and
      2:1:2:1, v/v), was successfully used in the reversed-phase mode. A scale-up
      process from analytical to semipreparative in a very short time was developed.
      The structures of isolated compounds were evaluated by high-performance liquid
      chromatography with diode array detection and electrospray ionization mass
      spectrometry, gas chromatography with mass spectrometry, and one- and two
      dimensional NMR spectroscopy. (8S,9R)-9-(3-Methylbutenoyloxy)-O-acetyl-8,9
      dihydrooroselol (compound B), (8S,9R)-9-(2-methyl-Z-butenoyloxy)-O-acetyl-8,9
      dihydrooroselol (edultin, compound C), and (8S,9R)-9-acetoxy-O-(2alpha
      methylbutyryl)-8,9-dihydrooroselol (compound D) were obtained using heptane/ethyl
      acetate/methanol/water (2:1:2:1, v/v) in <40 min. The method yielded 4.6 mg of a
      mixture of compounds B and C (11:89) and 3.7 mg of compound D. These amounts were
      obtained from the crude extract (0.5 g) in a single run. Although the compounds
      are known, their isolation by countercurrent chromatography and the analysis of
      their relative stereochemistry by two-dimensional NMR spectroscopy have been
      performed for the first time. Additionally, heptane/ethyl acetate/methanol/water
      (3:2:3:2, v/v) led to the isolation of oxypeucedanin (1.2 mg; compound A). This
      is the first time that angular dihydrofuranocoumarin was isolated from plant
      extract by countercurrent chromatography. 

PMID- 25380283
TI  - Head and Trunk Acceleration During Intermediate Transport on Medical Utility
      Vehicles.
AB  - OBJECTIVE: To compare head and trunk acceleration during transport on 2 medical
      utility vehicles. DESIGN: Within subject. SETTING: Controlled laboratory.
      PARTICIPANTS: Nineteen male volunteers (21.8 +/- 1.4 years, 176.5 +/- 5.5 cm,
      90.3 +/- 16.1 kg). INTERVENTIONS: Participants were secured to a spineboard and
      stretcher on the Husqvarna HUV 4421DXL ambulance (HUV) and modified John Deere
      Gator TH (Gator) and driven over synthetic field turf transitioning to concrete
      slab (interval 1) and concrete slab transitioning to natural grass (interval 2).
      Three-dimensional (x, y, and z) accelerometers recorded head and trunk
      acceleration. At each data point, acceleration of the trunk was subtracted from
      the acceleration of the head and the peak acceleration difference was determined.
      Independent variables were vehicle (HUV, Gator) and interval (interval 1,
      interval 2). MAIN OUTCOME MEASURES: The average peak acceleration differences in
      3 directions (x, y, z) were analyzed using a 2-factor within analysis of variance
      (P <= 0.05). RESULTS: For x, Gator in interval 2 (28.34 +/- 7.45 m/s/s) was
      greater than HUV in interval 2 (21.87 +/- 6.28 m/s/s), and HUV (11.05 +/- 3.29
      m/s/s) and Gator (12.56 +/- 4.32 m/s/s) in interval 1. The HUV in interval 2 was
      greater than HUV and Gator in interval 1. For z, Gator in interval 2 (22.12 +/-
      4.8 m/s/s) was greater than HUV in interval 2 (15.21 +/- 2.84 m/s/s), and HUV
      (9.51 +/- 3.01 m/s/s) and Gator (12.5 +/- 3.78 m/s/s) in interval 1. The HUV in
      interval 2 was greater than HUV and Gator in interval 1. Gator in interval 1 was
      greater than HUV in interval 1. CONCLUSIONS: Varying head and trunk accelerations
      exist in healthy spine-boarded participants during transport on medical utility
      vehicles dependent on surface and vehicle type. CLINICAL RELEVANCE: Intermediate
      transport vehicles vary in their ability to mitigate perturbations conveyed to
      the patient from the terrain travelled over.

PMID- 25380282
TI  - Does Visual Performance Influence Head Impact Severity Among High School Football
      Athletes?
AB  - OBJECTIVE: To compare the odds of sustaining moderate and severe head impacts,
      rather than mild, between high school football players with high and low visual
      performance. DESIGN: Prospective quasi-experimental. SETTING: Clinical Research
      Center/On-field. PARTICIPANTS: Thirty-seven high school varsity football players.
      INTERVENTIONS: Athletes completed the Nike SPARQ Sensory Station visual
      assessment before the season. Head impact biomechanics were captured at all
      practices and games using the Head Impact Telemetry System. MAIN OUTCOME
      MEASURES: Each player was classified as either a high or low performer using a
      median split for each of the following visual performance measures: visual
      clarity, contrast sensitivity, depth perception, near-far quickness, target
      capture, perception span, eye-hand coordination, go/no go, and reaction time. We
      computed the odds of sustaining moderate and severe head impacts against the
      reference odds of sustaining mild head impacts across groups of high and low
      performers for each of the visual performance measures. RESULTS: Players with
      better near-far quickness had increased odds of sustaining moderate [odds ratios
      (ORs), 1.27; 95% confidence intervals (CIs), 1.04-1.56] and severe head impacts
      (OR, 1.45; 95% CI, 1.05-2.01) as measured by Head Impact Technology severity
      profile. High and low performers were at equal odds on all other measures.
      CONCLUSIONS: Better visual performance did not reduce the odds of sustaining
      higher magnitude head impacts. Visual performance may play less of a role than
      expected for protecting against higher magnitude head impacts among high school
      football players. Further research is needed to determine whether visual
      performance influences concussion risk. CLINICAL RELEVANCE: Based on our results,
      we do not recommend using visual training programs at the high school level for
      the purpose of reducing the odds of sustaining higher magnitude head impacts.

PMID- 25380284
TI  - Ozone depletion and climate change: impacts on UV radiation.
AB  - We assess the importance of factors that determine the intensity of UV radiation
      at the Earth's surface. Among these, atmospheric ozone, which absorbs UV
      radiation, is of considerable importance, but other constituents of the
      atmosphere, as well as certain consequences of climate change, can also be major
      influences. Further, we assess the variations of UV radiation observed in the
      past and present, and provide projections for the future. Of particular interest
      are methods to measure or estimate UV radiation at the Earth's surface. These are
      needed for scientific understanding and, when they are sufficiently sensitive,
      they can serve as monitors of the effectiveness of the Montreal Protocol and its
      amendments. Also assessed are several aspects of UV radiation related to
      biological effects and health. The implications for ozone and UV radiation from
      two types of geoengineering methods that have been proposed to combat climate
      change are also discussed. In addition to ozone effects, the UV changes in the
      last two decades, derived from measurements, have been influenced by changes in
      aerosols, clouds, surface reflectivity, and, possibly, by solar activity. The
      positive trends of UV radiation observed after the mid-1990s over northern mid
      latitudes are mainly due to decreases in clouds and aerosols. Despite some
      indications from measurements at a few stations, no statistically significant
      decreases in UV-B radiation attributable to the beginning of the ozone recovery
      have yet been detected. Projections for erythemal irradiance (UVery) suggest the
      following changes by the end of the 21(st) century (2090-2100) relative to the
      present time (2010-2020): (1) Ozone recovery (due to decreasing ozone-depleting
      substances and increasing greenhouse gases) would cause decreases in UVery, which
      will be highest (up to 40%) over Antarctica. Decreases would be small (less than
      10%) outside the southern Polar Regions. A possible decline of solar activity
      during the 21(st) century might affect UV-B radiation at the surface indirectly
      through changes induced in stratospheric ozone. (2) The projected changes in
      cloud cover would lead to relatively small effects (less than 3%), except at
      northern high latitudes where increases in cloud cover could lead to decreases in
      UVery by up to 7%. (3) Reductions in reflectivity due to the melting of sea-ice
      in the Arctic would lead to decreases of UVery by up to 10%, while at the margins
      of the Antarctic the decreases would be smaller (2-3%). The melting of the sea
      ice would expose the ocean surface formerly covered by ice to UV-B radiation up
      to 10 times stronger than before. (4) The expected improvement of air-quality and
      reductions of aerosols over the most populated areas of the northern hemisphere
      may result in 10-20% increases in UVery, except over China where even larger
      increases are projected. The projected aerosol effect for the southern hemisphere
      is generally very small. Aerosols are possibly the most important factor for
      future UV levels over heavily populated areas, but their projected effects are
      the most uncertain. 

PMID- 25380285
TI  - Specific activation of dendritic cells enhances clearance of Bacillus anthracis
      following infection.
AB  - Dendritic cells are potent activators of the immune system and have a key role in
      linking innate and adaptive immune responses. In the current study we have used
      ex vivo pulsed bone marrow dendritic cells (BMDC) in a novel adoptive transfer
      strategy to protect against challenge with Bacillus anthracis, in a murine model.
      Pre-pulsing murine BMDC with either recombinant Protective Antigen (PA) or CpG
      significantly upregulated expression of the activation markers CD40, CD80, CD86
      and MHC-II. Passive transfusion of mice with pulsed BMDC, concurrently with
      active immunisation with rPA in alum, significantly enhanced (p<0.001) PA
      specific splenocyte responses seven days post-immunisation. Parallel studies
      using ex vivo DCs expanded from human peripheral blood and activated under the
      same conditions as the murine DC, demonstrated that human DCs had a PA dose
      related significant increase in the markers CD40, CD80 and CCR7 and that the
      increases in CD40 and CD80 were maintained when the other activating components,
      CpG and HK B. anthracis were added to the rPA in culture. Mice vaccinated on a
      single occasion intra-muscularly with rPA and alum and concurrently transfused
      intra-dermally with pulsed BMDC, demonstrated 100% survival following lethal B.
      anthracis challenge and had significantly enhanced (p<0.05) bacterial clearance
      within 2 days, compared with mice vaccinated with rPA and alum alone. 

PMID- 25380286
TI  - 25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid
      resistance in severe asthma exacerbation.
AB  - Oxidative stress plays a significant role in exacerbation of asthma. The role of
      vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed
      to determine the relationship between vitamin D status and oxidative stress in
      asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin
      D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D
      sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed
      lower forced expiratory volume in one second (FEV1) compared to that with V-D
      sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased
      TNF-alpha, OGG1 and NFkappaB expression and NFkappaB phosphorylation in severe
      asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of
      FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3
      inhibited LPS-induced ROS and DNA damage and were associated with a decline in
      TNF-alpha and NFkappaB in epithelial cells. H2O2 reduces nuclear translocation of
      glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment
      enhanced the dexamethasone-induced nuclear translocation of glucocorticoid
      receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3
      deficiency asthma patients. These findings indicate that V-D deficiency
      aggravates oxidative stress and DNA damage, suggesting a possible mechanism for
      corticosteroid resistance in severe asthma exacerbation. 

PMID- 25380287
TI  - Real-life GOLD 2011 implementation: the management of COPD lacks correct
      classification and adequate treatment.
AB  - Chronic obstructive pulmonary disease (COPD) is a serious, yet preventable and
      treatable, disease. The success of its treatment relies largely on the proper
      implementation of recommendations, such as the recently released Global Strategy
      for Diagnosis, Management, and Prevention of COPD (GOLD 2011, of late December
      2011). The primary objective of this study was to examine the extent to which
      GOLD 2011 is being used correctly among Czech respiratory specialists, in
      particular with regard to the correct classification of patients. The secondary
      objective was to explore what effect an erroneous classification has on
      inadequate use of inhaled corticosteroids (ICS). In order to achieve these goals,
      a multi-center, cross-sectional study was conducted, consisting of a general
      questionnaire and patient-specific forms. A subjective classification into the
      GOLD 2011 categories was examined, and then compared with the objectively
      computed one. Based on 1,355 patient forms, a discrepancy between the subjective
      and objective classifications was found in 32.8% of cases. The most common reason
      for incorrect classification was an error in the assessment of symptoms, which
      resulted in underestimation in 23.9% of cases, and overestimation in 8.9% of the
      patients' records examined. The specialists seeing more than 120 patients per
      month were most likely to misclassify their condition, and were found to have
      done so in 36.7% of all patients seen. While examining the subjectively driven
      ICS prescription, it was found that 19.5% of patients received ICS not according
      to guideline recommendations, while in 12.2% of cases the ICS were omitted,
      contrary to guideline recommendations. Furthermore, with consideration to the
      objectively-computed classification, it was discovered that 15.4% of patients
      received ICS unnecessarily, whereas in 15.8% of cases, ICS were erroneously
      omitted. It was therefore concluded that Czech specialists tend either to under
      prescribe or overuse inhaled corticosteroids. 

PMID- 25380288
TI  - Applying the community partnership approach to human biology research.
AB  - Contemporary human biology research employs a unique skillset for biocultural
      analysis. This skillset is highly appropriate for the study of health disparities
      because disparities result from the interaction of social and biological factors
      over one or more generations. Health disparities research almost always involves
      disadvantaged communities owing to the relationship between social position and
      health in stratified societies. Successful research with disadvantaged
      communities involves a specific approach, the community partnership model, which
      creates a relationship beneficial for researcher and community. Paramount is the
      need for trust between partners. With trust established, partners share research
      goals, agree on research methods and produce results of interest and importance
      to all partners. Results are shared with the community as they are developed;
      community partners also provide input on analyses and interpretation of findings.
      This article describes a partnership-based, 20 year relationship between
      community members of the Akwesasne Mohawk Nation and researchers at the
      University at Albany. As with many communities facing health disparity issues,
      research with Native Americans and indigenous peoples generally is inherently
      politicized. For Akwesasne, the contamination of their lands and waters is an
      environmental justice issue in which the community has faced unequal exposure to,
      and harm by environmental toxicants. As human biologists engage in more
      partnership-type research, it is important to understand the long term goals of
      the community and what is at stake so the research circle can be closed and
      'helicopter' style research avoided.

PMID- 25380289
TI  - Defining landscape resistance values in least-cost connectivity models for the
      invasive grey squirrel: a comparison of approaches using expert-opinion and
      habitat suitability modelling.
AB  - Least-cost models are widely used to study the functional connectivity of habitat
      within a varied landscape matrix. A critical step in the process is identifying
      resistance values for each land cover based upon the facilitating or impeding
      impact on species movement. Ideally resistance values would be parameterised with
      empirical data, but due to a shortage of such information, expert-opinion is
      often used. However, the use of expert-opinion is seen as subjective, human
      centric and unreliable. This study derived resistance values from grey squirrel
      habitat suitability models (HSM) in order to compare the utility and validity of
      this approach with more traditional, expert-led methods. Models were built and
      tested with MaxEnt, using squirrel presence records and a categorical land cover
      map for Cumbria, UK. Predictions on the likelihood of squirrel occurrence within
      each land cover type were inverted, providing resistance values which were used
      to parameterise a least-cost model. The resulting habitat networks were measured
      and compared to those derived from a least-cost model built with previously
      collated information from experts. The expert-derived and HSM-inferred least-cost
      networks differ in precision. The HSM-informed networks were smaller and more
      fragmented because of the higher resistance values attributed to most habitats.
      These results are discussed in relation to the applicability of both approaches
      for conservation and management objectives, providing guidance to researchers and
      practitioners attempting to apply and interpret a least-cost approach to mapping
      ecological networks. 

PMID- 25380291
TI  - Influence of combined dust reducing carpet and compact air filtration unit on the
      indoor air quality of a classroom.
AB  - Primary schools mostly rely on natural ventilation but also have an interest in
      affordable technology to improve indoor air quality (IAQ). Laboratory tests show
      promising results for dust reducing carpets and compact air filtration systems
      but there is no information available on the performance of these interventions
      in actual operating classrooms. An exploratory study was performed to evaluate a
      combination of the two systems in a primary school. Measurements of PM-10 and PM
      2.5 were performed by filter sampling and aerosol spectrometry. Other IAQ
      parameters included black smoke (BS), volatile organic compounds (VOC), nitrogen
      dioxide (NO2) and formaldehyde. Both interventions were introduced in one
      classroom during one week, using another classroom as a reference. In a second
      week the interventions were moved to the other classroom, using the first as a
      reference (cross-over design). In three remaining weeks the classrooms were
      compared without interventions. Indoor IAQ parameters were compared to the
      corresponding outdoor parameters using the indoor/outdoor (I/O) ratio. When the
      classrooms were occupied (teaching hours) interventions resulted in 27-43%
      reductions of PM-10, PM-2.5 and BS values. During the weekends the systems
      reduced these levels by 51-87%. Evaluations using the change in I/O ratios gave
      comparable results. Levels of VOC, NO2 and formaldehyde were rather low and a
      contribution of the interventions to the improvement of these gas phase IAQ
      parameters was inconclusive. 

PMID- 25380290
TI  - Combining forces--the use of Landsat TM satellite imagery, soil parameter
      information, and multiplex PCR to detect Coccidioides immitis growth sites in
      Kern County, California.
AB  - Coccidioidomycosis is a fungal disease acquired through the inhalation of spores
      of Coccidioides spp., which afflicts primarily humans and other mammals. It is
      endemic to areas in the southwestern United States, including the San Joaquin
      Valley portion of Kern County, California, our region of interest (ROI).
      Recently, incidence of coccidioidomycosis, also known as valley fever, has
      increased significantly, and several factors including climate change have been
      suggested as possible drivers for this observation. Up to date details about the
      ecological niche of C. immitis have escaped full characterization. In our
      project, we chose a three-step approach to investigate this niche: 1) We examined
      Landsat-5-Thematic-Mapper multispectral images of our ROI by using training
      pixels at a 750 m * 750 m section of Sharktooth Hill, a site confirmed to be a C.
      immitis growth site, to implement a Maximum Likelihood Classification scheme to
      map out the locations that could be suitable to support the growth of the
      pathogen; 2) We used the websoilsurvey database of the US Department of
      Agriculture to obtain soil parameter data; and 3) We investigated soil samples
      from 23 sites around Bakersfield, California using a multiplex Polymerase Chain
      Reaction (PCR) based method to detect the pathogen. Our results indicated that a
      combination of satellite imagery, soil type information, and multiplex PCR are
      powerful tools to predict and identify growth sites of C. immitis. This approach
      can be used as a basis for systematic sampling and investigation of soils to
      detect Coccidioides spp.

PMID- 25380292
TI  - Order parameter and connectivity topology analysis of crystalline ceramics for
      nuclear waste immobilization.
AB  - We apply bond order and topological methods to the problem of analysing the
      results of radiation damage cascade simulations in ceramics. Both modified
      Steinhardt local order and connectivity topology analysis techniques provide
      results that are both translationally and rotationally invariant and which do not
      rely on a particular choice of a reference structure. We illustrate the methods
      with new analyses of molecular dynamics simulations of single cascades in the
      pyrochlores Gd(2)Ti(2)O(7) and Gd(2)Zr(2)O(7) similar to those reported
      previously (Todorov et al 2006 J. Phys.: Condens. Matter 18 2217). Results from
      the Steinhardt and topology analyses are consistent, while often providing
      complementary information, since the Steinhardt parameters are sensitive to
      changes in angular arrangement even when the overall topological connectivity is
      fixed. During the highly non-equilibrium conditions at the start of the cascade,
      both techniques reveal significant localized transient structural changes and
      variation in the cation connectivity. After a few picoseconds, the connectivity
      is largely fixed, while the order parameters continue to change. In the zirconate
      there is a shift to the anion disordered system while in the titanate there is
      substantial reversion and healing back to the parent pyrochlore structure.

PMID- 25380293
TI  - Changes in anti-thyroglobulin IgG glycosylation patterns in Hashimoto's
      thyroiditis patients.
AB  - OBJECTIVE: Sera of Hashimoto's thyroiditis (HT) patients are known to exhibit
      elevated levels of anti-thyroglobulin IgG (TgAb IgG). Therefore, TgAb IgG
      represents a hallmark of this debilitating autoimmune disease. The aim of our
      study was to investigate the differential expression of specific glycosylation
      patterns of TgAb IgG from HT patients and healthy blood donors. METHODS: HT
      patients (n = 32) were divided into two subgroups, medium level group (mHT, n =
      15) and high level group (hHT, n = 17), according to the serum levels of TgAb
      detected by electrochemiluminescence immunoassay. TgAb IgG was purified by
      affinity chromatography from the sera of the HT group and control group (n = 15).
      MALDI-QIT-TOF-MS/MS spectrometry was performed to identify the glycosylation
      profiles of purified TgAb IgG. Lectin microarray technology was used to compare
      the abundance of different glycans found on TgAb IgG between HT patients and
      controls, and between the mHT and hHT groups. RESULTS: The results by MALDI-QIT
      TOF-MS/MS showed that the glycosylation profiles of TgAb IgG were similar between
      the mHT, hHT, and control groups. Furthermore, the lectin microarray showed that
      compared to the control group (all P < .001), there were higher levels present of
      (1) mannose (detected as lectin LCA, VFA, and MNA-M); (2) terminal sialic acid
      (detected as SNA-I and PSA); (3) core fucose (detected as LcH); and (4) Gal(beta1
      4)GlcNAc(beta1-2)Man glycans (detected as PHA-L) on TgAb IgG from the HT group. A
      similar trend was observed between the hHT and mHT group, with elevated levels of
      mannose, terminal sialic acid, core fucose, and Gal(beta1-4)GlcNAc(beta1-2)Man
      glycans on TgAb IgG found in the hHT group compared with the mHT group (all P <
      .05). CONCLUSIONS: TgAb IgG of HT patients exhibits higher glycosylation levels
      than those observed for TgAb IgG of healthy controls. Our results provide new
      clues for exploring the role of TgAb in the pathogenesis of HT.

PMID- 25380294
TI  - Vitamin d and physical activity status: associations with five-year changes in
      body composition and muscle function in community-dwelling older adults.
AB  - CONTEXT: High vitamin D and physical activity (PA) levels are independently
      associated with improved body composition and muscle function in older adults.
      OBJECTIVE: The objective of this study was to investigate the interaction of 25
      hydroxyvitamin D (25OHD) and PA status in maintenance of body composition and
      muscle function in older adults. DESIGN AND SETTING: This was a 5-year
      prospective population-based study of Australian community-dwelling older adults.
      PARTICIPANTS: Participants in the study included 615 community-dwelling
      volunteers aged 50 years old or older [61.4 +/- 6.9 (mean +/- SD) y; 48% female]
      randomly selected from electoral rolls and categorized according to baseline
      serum 25OHD (>= or <50 nmol/L) and PA (>= or <10,000 pedometer determined
      steps/d) levels as follows: high 25OHD and high PA (VitD+PA+); high 25OHD and low
      PA (VitD+PA-); low 25OHD and high PA (VitD-PA+); and low 25OHD and low PA (VitD
      PA-). A subset of 518 participants completed accelerometer assessments during
      follow-up. MAIN OUTCOME MEASURES: Changes in dual-energy X-ray absorptiometry
      assessed body composition and lower-limb muscle function were measured. RESULTS:
      VitD+PA+ had significantly smaller increases in body fat over 5 years compared
      with other groups (all P < .05). Higher baseline pedometer-determined PA resulted
      in declines in total body fat (beta = -.23 kg per 100 steps/d, P = .001) over 5
      years for participants with high 25OHD but not those with low 25OHD (P > .05).
      Among participants with accelerometer data, these associations were generally
      mediated by higher levels of moderate/vigorous PA. CONCLUSIONS: High vitamin D
      status appears to enhance PA-related declines in body fat during aging, but the
      mechanism may be greater amounts of outdoor moderate/vigorous PA rather than a
      direct effect of 25OHD.

PMID- 25380295
TI  - HLA class I and class II associations with ESRD in Saudi Arabian population.
AB  - BACKGROUND: Chronic renal failure (CRF) leads in the majority of instances to end
      stage renal disease (ESRD) requiring renal replacement therapy. Our interest was
      to evaluate the possible associations of HLA class I and class II antigens with
      ESRD independent of other factors, in Saudi Arabia population. METHODOLOGY: A
      retrospective study to determine the HLA class I and class II polymorphisms and
      their association with ESRD, was performed on 350 patients with ESRD, and 105
      healthy unrelated control. Patients and control groups were typed by SSOP lumenix
      techniques. The alleles positively associated to the ESRD were: HLA-B*15, B*18,
      B*49 - DRB1*03, negatively associated alleles were A*26, HLA-B*39, B*50. The
      haplotypes positively associated with ESRD were: HLA-A*01-DRB1*13 and HLA-A*30
      DRBI*03. The negatively associated haplotypes were: HLA-A*02-B*39, A*02-B*50,
      A*24-B*35, A*24-B*58, A*24-DRB1*16, A*68-DRB1*04, A*02-DQB1*03, A*29-DQB1*02,
      A*29-DOB1*05 and B*27-DRB1*07 and the last one is the most significant protective
      haplotypes. CONCLUSION: The high Relative Risk (RR) observed and its statistical
      correlation reflect the strength of the described association between HLA
      antigens and ESRD.

PMID- 25380296
TI  - The effect of vigorous physical activity and body composition on cortical bone
      mass in adolescence.

PMID- 25380297
TI  - Excited-state proton transfer of photoacids adsorbed on biomaterials.
AB  - The interaction between a photoacid (8-hydroxy-1,3,6-pyrenetrisulfonate, HPTS)
      and the surfaces of biomaterials and the diffusion of protons along the
      biomaterial surfaces were examined by following the excited-state proton transfer
      (ESPT) from the photoacid, adsorbed on the surfaces, to water molecules next to
      it. We chose two different types of biomaterial surfaces, hydrophobic insulin
      amyloid fibrils and hydrophilic cellulose surfaces. With the help of steady-state
      and time-resolved fluorescence techniques, we found that the rate of ESPT from
      HPTS on insulin fibrils to adjacent water molecules is about 1/10 that in bulk
      water. However, the proton geminate recombination takes place with an efficiency
      similar to that in bulk water. ESPT from HPTS in wet cellulose to water depends
      on the weight percentage of water adsorbed by the cellulose. In a semidry sample
      (<100% weight percentage of water), the ESPT rate is rather low and thus the
      quantum efficiency of the ESPT is also low within the excited-state lifetime.
      When the water content is higher, the ESPT rate is almost that of bulk water. We
      explain these results by the existence of pools of water in cellulose of high
      water content, in which the triple-negatively charged HPTS molecules desorb from
      the cellulose surface to these pools. The use of HPTS has allowed us to examine
      the biological surface and its interaction with water molecules, while obtaining
      important information regarding the hydration state of the surface that otherwise
      could not have been obtained. The model that we propose here for the use of
      photoacids to follow the hydrated state of a given surface is a promising new
      method of examining the interaction of water molecules with biological surfaces.

PMID- 25380298
TI  - Life-cycle fossil energy consumption and greenhouse gas emissions of bioderived
      chemicals and their conventional counterparts.
AB  - Biomass-derived chemical products may offer reduced environmental impacts
      compared to their fossil-derived counterparts and could improve profit margins at
      biorefineries when coproduced with higher-volume, lower-profit margin biofuels.
      It is important to assess on a life-cycle basis the energy and environmental
      impacts of these bioproducts as compared to conventional, fossil-derived
      products. We undertook a life-cycle analysis of eight bioproducts produced from
      either algal-derived glycerol or corn stover-derived sugars. Selected on the
      basis of technology readiness and market potential, the bioproducts are propylene
      glycol, 1,3-propanediol, 3-hydroxypropionic acid, acrylic acid, polyethylene,
      succinic acid, isobutanol, and 1,4-butanediol. We developed process simulations
      to obtain energy and material flows in the production of each bioproduct and
      examined sensitivity of these flows to process design assumptions. Conversion
      process data for fossil-derived products were based on the literature. Conversion
      process data were combined with upstream parameters in the Greenhouse gases,
      Regulated Emissions, and Energy use in Transportation (GREET) model to generate
      life-cycle greenhouse gas (GHG) emissions and fossil energy consumption (FEC) for
      each bioproduct and its corresponding petroleum-derived product. The bioproducts
      uniformly offer GHG emissions reductions compared to their fossil counterparts
      ranging from 39 to 86% on a cradle-to-grave basis. Similarly, FEC was lower for
      bioproducts than for conventional products. 

PMID- 25380299
TI  - Methyl effect in azumamides provides insight into histone deacetylase inhibition
      by macrocycles.
AB  - Natural, nonribosomal cyclotetrapeptides have traditionally been a rich source of
      inspiration for design of potent histone deacetylase (HDAC) inhibitors. We
      recently disclosed the total synthesis and full HDAC profiling of the naturally
      occurring azumamides ( J. Med. Chem. 2013 , 56 , 6512 ). In this work, we
      investigate the structural requirements for potent HDAC inhibition by macrocyclic
      peptides using the azumamides along with a series of unnatural analogues obtained
      through chemical synthesis. By solving solution NMR structures of selected
      macrocycles and combining these findings with molecular modeling, we pinpoint
      crucial enzyme-ligand interactions required for potent inhibition of HDAC3.
      Docking of additional natural products confirmed these features to be generally
      important. Combined with the structural conservation across HDACs 1-3, this
      suggests that while cyclotetrapeptides have provided potent and class-selective
      HDAC inhibitors, it will be challenging to distinguish between the three major
      class I deacetylases using these chemotypes. 

PMID- 25380301
TI  - How compatible are participatory ergonomics programs with occupational health and
      safety management systems?
AB  - OBJECTIVES: Musculoskeletal disorders (MSD) are a major cause of pain,
      disability, and costs. Prevention of MSD at work is frequently described in terms
      of implementing an ergonomics program, often a participatory ergonomics (PE)
      program. Most other workplace injury prevention activities take place under the
      umbrella of a formal or informal occupational health and safety management system
      (OHSMS). This study assesses the similarities and differences between OHSMS and
      PE as such knowledge could help improve MSD prevention activities. Methods Using
      the internationally recognized Occupational Health and Safety Assessment Series
      (OHSAS 18001), 21 OHSMS elements were extracted. In order to define PE
      operationally, we identified the 20 most frequently cited papers on PE and
      extracted content relevant to each of the OHSAS 18001 elements. RESULTS: The PE
      literature provided a substantial amount of detail on five elements: (i) hazard
      identification, risk assessment and determining controls; (ii) resources, roles,
      responsibility, accountability, and authority; (iii) competence, training and
      awareness; (iv) participation and consultation; and (v) performance measurement
      and monitoring. However, of the 21 OHSAS elements, the PE literature was silent
      on 8 and provided few details on 8 others. CONCLUSIONS: The PE literature did not
      speak to many elements described in OHSMS and even when it did, the language used
      was often different. This may negatively affect the effectiveness and
      sustainability of PE initiatives within organizations. It is expected that paying
      attention to the approaches and language used in management system frameworks
      could make prevention of MSD activities more effective and sustainable.

PMID- 25380300
TI  - Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver
      fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression.
AB  - Hepatocyte growth factor (HGF) gene transfer inhibits liver fibrosis by
      regulating aberrant cellular functions, while mutant matrix metalloproteinase-9
      (mMMP-9) enhances matrix degradation by neutralizing the elevated tissue
      inhibitor of metalloproteinase-1 (TIMP-1). It was shown that ASH1 and EZH2
      methyltransferases are involved in development of liver fibrosis; however, their
      role in the resolution phase of liver fibrosis has not been investigated. This
      study evaluated the role of ASH1 and EZH2 in two mechanistically different
      therapeutic modalities, HGF and mMMP-9 gene transfer in CCl4 induced rat liver
      fibrosis. Liver fibrosis was induced in rats with twice a week intraperitoneal
      injection of CCl4 for 8 weeks. Adenovirus vectors encoding mMMP-9 or HGF genes
      were injected through tail vein at weeks six and seven and were sacrificed one
      week after the second injection. A healthy animal group was likewise injected
      with saline to serve as a negative control. Rats treated with mMMP-9 showed
      significantly lower fibrosis score, less Sirius red stained collagen area,
      reduced hydroxyproline and ALT concentration, decreased transforming growth
      factor beta 1 (TGF-beta1) mRNA and lower labeling indices of alpha smooth muscle
      actin (alpha-SMA) and proliferating cell nuclear antigen (PCNA) stained cells
      compared with HGF- or saline-treated rats. Furthermore, TIMP-1 protein expression
      in mMMP-9 group was markedly reduced compared with all fibrotic groups. ASH1 and
      EZH2 protein expression was significantly elevated in fibrotic liver and
      significantly decreased in mMMP-9- and HGF-treated compared to saline-treated
      fibrotic livers with further reduction in the mMMP-9 group. CONCLUSION: Gene
      transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2
      methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which
      underlines the central role of these enzymes during fibrogenesis. Future studies
      should evaluate the role of selective pharmacologic inhibitors of ASH1 and EZH2
      in resolution of liver fibrosis.

PMID- 25380302
TI  - Transsclera Drug Delivery by Pulsed High-Intensity Focused Ultrasound (HIFU): An
      Ex Vivo Study.
AB  - PURPOSE/AIM OF STUDY: Drug delivery to the ocular posterior segment is of
      importance, but it is a challenge in the treatment of irreversible blindness
      disease, such as age-related macular degeneration. Although some methods (i.e.
      intraocular injection, sustained release by polymer and iontophoresis) have been
      applied, some technical drawbacks, such as slow rate and damage to the eye, need
      to be overcome for wide use. MATERIALS AND METHODS: In this study, the
      feasibility of high-intensity focused ultrasound (HIFU) to enhance the
      transsclera drug delivery was tested for the first time. One-hundred HIFU pulses
      with the driving frequency of 1.1 MHz, acoustic power of 105.6 W, pulse duration
      of 10-50 ms and pulse repetition frequency of 1 Hz were delivered to the fresh ex
      vivo porcine sclera specimen. RESULTS: In comparison to the passive diffusion
      (control), 50-ms HIFU can increase the penetration depth by 2.0 folds (501.7 +/-
      126.4 um versus 252.4 +/- 29.2 um) using bicinchoninic acid assay and Rhodamine 6
      G fluorescence intensity by 3.1 folds (22.4 +/- 12.3 versus 7.1 +/- 4.1) and
      coverage area by 2.6 folds (40.4 +/- 9.1% versus 15.8 +/- 2.9%). No morphological
      changes on the sonicated sclera samples were found using a surface electron
      microscope. CONCLUSIONS: In summary, pulsed-HIFU may be an effective modality in
      the transsclera drug delivery with a high transporting rate and depth. In vivo
      studies are necessary to further evaluate its performance, including the drug
      penetration and its possible side effects.

PMID- 25380303
TI  - CD117 expression in fibroblasts-like stromal cells indicates unfavorable clinical
      outcomes in ovarian carcinoma patients.
AB  - The stem cell factor (SCF) receptor CD117 (c-kit), is widely used for
      identification of hematopoietic stem cells and cancer stem cells. Moreover, CD117
      expression in carcinoma cells indicates a poor prognosis in a variety of cancers.
      However the potential expression in tumor microenvironment and the biological and
      clinical impact are currently not reported. The expression of CD117 was
      immunohistochemically evaluated in a serial of 242 epithelial ovarian cancer
      (EOC) cases. Thirty-eight out of 242 cases were CD117 positive in fibroblast-like
      stromal cells and 22 cases were positive in EOC cells. Four cases were both
      positive in fibroblast-like stromal cells and EOC cells for CD117. CD117
      expression in fibroblast-like stromal cells in ovarian carcinoma was closely
      linked to advanced FIGO stage, poor differentiation grade and histological
      subtype (p<0.05), and it was significantly associated with poor overall survival
      (OS) and progression free survival (PFS) (Kaplan-Meier analysis; p<0.05, log-rank
      test). CD117 expression in ovarian carcinoma cells was not associated with these
      clinicopathological variables. The CD117 positive fibroblast-like stromal cells
      were all positive for mesenchymal stem/stromal cell (MSC) marker CD73 but
      negative for fibroblast markers fibroblast activation protein (FAP) and alpha
      smooth muscle actin (alpha-SMA), indicating that the CD117+/CD73+ fibroblast-like
      stromal cells are a subtype of mesenchymal stem cells in tumor stroma, although
      further characterization of these cells are needed. It is concluded herewith that
      the presence of CD117+/CD73+ fibroblast-like stromal cells in ovarian carcinoma
      is an unfavorable clinical outcome indication. 

PMID- 25380304
TI  - Dental status of new caledonian children: is there a need for a new oral health
      promotion programme?
AB  - BACKGROUND: Before implementing a new oral health promotion program in the French
      overseas territory of Nouvelle Caledonie, the health authorities needed recent
      data about dental status of the New Caledonian child population. OBJECTIVES: This
      study aimed to describe the dental status of 6, 9 and 12-yr-old New Caledonian
      children and to investigate the environmental and behavioural risk factors
      related to oral health. METHODS: A randomly selected sample of 2734 children (744
      6-yr-olds, 789 9-yr-olds, and 1201 12-yr-olds) was examined clinically by seven
      calibrated investigators and participants responded to a questionnaire. The main
      variables were objective criteria about dental status and subjective criteria
      about experience of dental care, dental fear, self-perception of oral health,
      cultural or ethnic identity and environmental and behavioural risk factors.
      RESULTS: Overall, most of the children had infectious oral diseases: more than
      50% had gingivitis, and 60% of 6- and 9 yr-olds had at least one deciduous or
      permanent tooth with untreated caries. The mean 12-yr-old number of decayed
      missing and filled teeth (DMFT) was 2.09+/-2.82. The number of carious lesions
      was related to the unfavourable lifestyle, deprived social status and no
      preventive dental care. Kanak, Polynesians and Caledonians (respectively 27%, 18%
      and 45% of the study sample) were more affected by caries than metropolitan
      French and Asian children. Children with many untreated carious lesions had
      negative perceptions of their oral health; they complained of chewing difficulty
      and had higher scores for dental anxiety. CONCLUSION: This study highlights the
      need for new strategies aimed at improving oral health and at reducing
      inequalities in New Caledonia. An oral health promotion program would need to be
      developed in connection with other health programmes using the common risk factor
      approach within the context of the local environment.

PMID- 25380305
TI  - A Comparison of the Immunochemical Methods, PETINIA and EMIT, With That of HPLC
      UV for the Routine Monitoring of Mycophenolic Acid in Heart Transplant Patients.
AB  - BACKGROUND: The aim of this study was to evaluate particle enhanced turbidimetric
      inhibition immunoassay (PETINIA) recently developed for mycophenolic acid (MPA)
      determination in plasma and to compare it with a reference high-performance
      liquid chromatography (HPLC) method, using samples from heart transplant
      recipients. The results are presented in the context of PETINIA being compared
      with enzyme multiplied immunoassay technique (EMIT). METHODS: PETINIA evaluation
      was performed using 194 routine trough plasma samples at steady state. EMIT was
      evaluated using 677 samples from 61 steady-state 12-hour profiles obtained from
      35 heart transplant patients. Evaluation was undertaken on a Dimension EXL 200
      analyzer (PETINIA) and on a Viva-E analyzer (EMIT). RESULTS: The mean MPA
      concentration measured by PETINIA was significantly higher than that measured by
      high-performance liquid chromatography combined with UV detector (2.36 +/- 1.30
      mcg/mL versus 1.82 +/- 1.23 mcg/mL, respectively, P < 0.0001). Bland-Altman
      analysis revealed a mean bias of 0.54 mcg/mL [95% confidence interval (CI), 0.49
      0.59] comprising 33.48% (95% CI, 30.34-36.61). Passing-Bablok regression was: y =
      1.100x + 0.38 (95% CI for slope: 1.044-1.154 and for intercept: 0.30-0.47).
      Regardless of a significant observed correlation (r = 0.9230, P < 0.0001), the
      statistical analyses showed a significant difference between PETINIA and the
      reference chromatographic method. The mean MPA concentration measured by EMIT was
      significantly higher than that measured by HPLC (7.48 +/- 8.34 mcg/mL versus 5.57
      +/- 6.61 mcg/mL, respectively, P < 0.0001) with a mean bias of 1.91 mcg/mL (95%
      CI, 1.75-2.07) comprising 35.91% (95% CI, 34.37-37.45). The significant
      difference between EMIT and HPLC was confirmed by Passing-Bablok regression: y =
      1.300x + 0.24 (95% CI for slope: 1.279-1.324 and for intercept: 0.18-0.29). The
      analysis of the determinations, grouped by sampling time, revealed positive bias
      between EMIT and HPLC ranging from 24.54% to 42.77% and inversely proportional to
      MPA concentrations with r = 0.9122 (P < 0.001). CONCLUSIONS: The new
      immunochemical PETINIA method was associated with significantly higher MPA
      concentrations in routine therapeutic drug monitoring samples from heart
      transplant patients. The magnitude of the MPA overestimation was similar to that
      observed by use of the EMIT method.

PMID- 25380306
TI  - Biocompatible ionic liquid-biopolymer electrolyte-enabled thin and compact
      magnesium-air batteries.
AB  - With the surge of interest in miniaturized implanted medical devices (IMDs),
      implantable power sources with small dimensions and biocompatibility are in high
      demand. Implanted battery/supercapacitor devices are commonly packaged within a
      case that occupies a large volume, making miniaturization difficult. In this
      study, we demonstrate a polymer electrolyte-enabled biocompatible magnesium-air
      battery device with a total thickness of approximately 300 MUm. It consists of a
      biocompatible polypyrrole-para(toluene sulfonic acid) cathode and a bioresorbable
      magnesium alloy anode. The biocompatible electrolyte used is made of choline
      nitrate (ionic liquid) embedded in a biopolymer, chitosan. This polymer
      electrolyte is mechanically robust and offers a high ionic conductivity of 8.9 *
      10(-3) S cm(-1). The assembled battery delivers a maximum volumetric power
      density of 3.9 W L(-1), which is sufficient to drive some types of IMDs, such as
      cardiac pacemakers or biomonitoring systems. This miniaturized, biocompatible
      magnesium-air battery may pave the way to a future generation of implantable
      power sources.

PMID- 25380307
TI  - Mangiferin activates the Nrf2-ARE pathway and reduces etoposide-induced DNA
      damage in human umbilical cord mononuclear blood cells.
AB  - CONTEXT: Mangiferin (2-C-beta-d-gluco-pyranosyl-1,3,6,7-tetrahydroxyxanthone) is
      a well-known natural antioxidant distributed in various plants of the
      Anacardiaceae and Gentianaceae families. Mangiferin can inhibit carcinogen
      induced lung or colon tumor formation in experimental animals. However, the
      molecular mechanisms of its chemopreventive activity remain unexplored.
      OBJECTIVE: This study aimed to investigate the effects of mangiferin on chemical
      carcinogen-induced DNA damage and Nrf2-ARE signaling in hematopoietic cells.
      MATERIALS AND METHODS: Mononuclear cells (MNCs) were isolated from human
      umbilical cord blood (hUCB). DNA damage was evaluated by comet and micronucleus
      assays. The expression of Nrf2 and NQO1 was examined by immunofluorescence and
      western blotting. An electrophoretic mobility shift assay (EMSA) was used to
      detect the binding activity of Nrf2 with NQO1-ARE sequences. RESULTS: We found
      that mangiferin treatment significantly reduced DNA damage in etoposide-treated
      MNCs, which was verified by decreased olive tail moment (OTM) and micronucleus
      (MN) frequency. Mangiferin treatment significantly promoted Nrf2 translocation
      into the nucleus and increased nuclear Nrf2 expression. Moreover, NQO1, an Nrf2
      signaling target, was significantly upregulated by mangiferin treatment, and the
      binding activity of Nrf2 with NQO1-ARE sequences was elevated after mangiferin
      treatment. DISCUSSION AND CONCLUSION: Mangiferin activated Nrf2 signaling,
      upregulated NQO1 expression, and significantly reduced etoposide-induced DNA
      damage. Thus, mangiferin is a potential cytoprotective agent for hematopoietic
      cells.

PMID- 25380309
TI  - Total synthesis of muricadienin, the putative key precursor in the solamin
      biosynthesis.
AB  - The first total synthesis of muricadienin, the unsaturated putative precursor in
      the biosynthesis of trans- and cis-solamin is described. Key steps in the
      synthesis are a chemoselective hydroboration, a Z-selective Wittig reaction, and
      a Fries rearrangement for introducing the terminal alpha-substituted butenolide.
      Thus, muricadienin can be synthesized in 11 steps from commercially available
      starting materials in 42% overall yield. 

PMID- 25380310
TI  - Evidence of unfolded protein translocation through a protein nanopore.
AB  - Protein nanopores are mainly used to study transport, unfolding, intrinsically
      disordered proteins, protein-pore interactions, and protein-ligand complexes.
      This single-molecule sensor for biomedical and biotechnological applications is
      promising but until now direct proof of protein translocation through a narrow
      channel is lacking. Here, we report the translocation of a chimera molecule
      through the aerolysin nanopore in the presence of a denaturing agent, guanidium
      chloride (1.5 M) and KCl (1 M). The chimera molecule is composed of the
      recombinant MalE protein with a unique cysteine residue at the C-terminal
      position covalently linked to a single-stranded DNA oligonucleotide. Real-time
      polymerase chain reaction (PCR) was used to detect the presence of chimera
      molecules that have been effectively translocated from the cis to trans chamber
      of the set up. Comparing the electrical signature of the chimera related to the
      protein or oligonucleotide alone demonstrates that each type of molecule displays
      different dynamics in term of transport time, event frequency, and current
      blockade. This original approach provides the possibility to study protein
      translocation through different biological, artificial, and biomimetic nanopores
      or nanotubes. New future applications are now conceivable such as protein
      refolding at the nanopore exit, peptides and protein sequencing, and peptide
      characterization for diagnostics. 

PMID- 25380308
TI  - Seeking health information and support online: does it differ as a function of
      engagement in risky health behaviors? Evidence from the health information
      national trends survey.
AB  - BACKGROUND: The Internet is an important tool to deliver health behavior
      interventions, yet little is known about Internet access and use of health
      related information, or support, by the intended intervention recipients.
      OBJECTIVE: Our aim was to evaluate whether health-related Internet use differed
      as a function of common health-risk behaviors (excessive alcohol consumption,
      smoking, low fruit/vegetable intake, inactive/sedentary lifestyle, unprotected
      sun exposure, or obesity). METHODS: Sociodemographic, health behavior
      characteristics, and information on Internet access and use were assessed in the
      nationally representative US Health Information National Trends Survey (HINTS) 4.
      Data from 3911 participants collated in 2011/12 were included. RESULTS: Of the
      78.2% (95% CI 76.1-80.1) of participants who had ever accessed the Internet,
      approximately three-quarters (78.2%, 95% CI 75.4-80.7) had obtained health
      related information online last year. About half had used the Internet as the
      first source of health-related information (47.8%, 95% CI 44.8-50.7) or to access
      behavioral support (56.9%, 95% CI 53.7-60.0) in the last year. Adjusting for
      sociodemographic determinants of going online (being younger, white, female, with
      at least college education) revealed few differences in Internet access and use
      between health-risk behaviors. Participants with inadequate sun protection were
      less likely to access the Internet (OR 0.59, 95% CI 0.04-0.88) and those with low
      fruit/vegetable intake were less likely to have gone online to obtain health
      related information last year (OR 0.60, 95% CI 0.45-0.80). Smokers in particular
      were likely to use the Internet to obtain behavioral support (OR 1.90, 95% CI
      1.35-2.68). CONCLUSIONS: Internet access and use to obtain health-related
      information and support is widespread and mostly independent of engagement in
      various health-risk behaviors. However, those with low fruit/vegetable intake or
      inadequate sun-protective behaviors may be more difficult to reach with Internet
      based interventions. In addition, when developing online health promotions,
      relevant sociodemographic determinants of Internet use need to be targeted to
      maximize their impact.

PMID- 25380311
TI  - Transforming growth factor beta 1 augments calvarial defect healing and promotes
      suture regeneration.
AB  - BACKGROUND: Repair of complex cranial defects is hindered by a paucity of
      appropriate donor tissue. Bone morphogenetic protein 2 (BMP2) and transforming
      growth factor beta 1 (TGFbeta1) have been shown separately to induce bone
      formation through physiologically distinct mechanisms and potentially improve
      surgical outcome for cranial defect repair by obviating the need for donor
      tissue. We hypothesize that a combination of BMP2 and TGFbeta1 would improve
      calvarial defect healing by augmenting physiologic osteogenic mechanisms.
      METHODS/RESULTS: Coronal suturectomies (3*15 mm) were performed in 10-day-old New
      Zealand White rabbits. DermaMatrixTM (3*15mm) patterned with four treatments
      (vehicle, 350 ng BMP2, 200 ng TGFbeta1, or 350 ng BMP2+200 ng TGFbeta1) was
      placed in suturectomy sites and rabbits were euthanized at 6 weeks of age. Two
      dimensional (2D) defect healing, bone volume, and bone density were quantified by
      computed tomography. Regenerated bone was qualitatively assessed histologically.
      One-way analysis of variance revealed significant group main effects for all bone
      quantity measures. Analysis revealed significant differences in 2D defect
      healing, bone volume, and bone density between the control group and all
      treatment groups, but no significant differences were detected among the three
      growth factor treatment groups. Qualitatively, TGFbeta1 treatment produced bone
      with morphology most similar to native bone. TGFbeta1-regenerated bone contained
      a suture-like tissue, growing from the lateral edge of the defect margin toward
      the midline. Unique to the BMP2 treatment group, regenerated bone contained
      lacunae with chondrocytes, demonstrating the presence of endochondral
      ossification. CONCLUSIONS/SIGNIFICANCE: Total healing in BMP2 and TGFbeta1
      treatment groups is not significantly different. The combination of BMP2+TGFbeta1
      did not significantly increase bone healing compared with treatment with BMP2 or
      TGFbeta1 alone postoperatively at 4 weeks. We highlight the potential use of
      TGFbeta1 to regenerate calvarial bone and cranial sutures. TGFbeta1 therapy
      significantly augmented bony defect healing at an earlier time point when
      compared with control, regenerated bone along the native intramembranous
      ossification pathway, and (unlike BMP2 alone or in combination with TGFbeta1)
      permitted normal suture reformation. We propose a novel method of craniofacial
      bone regeneration using low-dose, spatially controlled growth factor therapies to
      minimize potentially harmful effects while maximizing local bioavailability and
      regenerating native tissues.

PMID- 25380316
TI  - Influence of N-alkylpyridinium halide based ionic liquids on micellization of
      P123 in aqueous solutions: a SANS, DLS, and NMR study.
AB  - The isotropic micellar state of Pluronic P123 in the presence and absence of N
      alkylpyridinium halide ionic liquids (ILs) is investigated using SANS, DLS, and
      (1)H NMR studies. The micellar structural parameters are obtained as a function
      of variation in alkyl chain length, anions, and concentrations of ILs by fitting
      the SANS scattering data with a model composed of core-shell form factor and a
      hard sphere structure factor of interaction. Addition of ILs decreases the
      micellar core, aggregation number, and hard sphere radius of P123 micelles. From
      quantitative analysis, we determined the amount of solvent (D2O + IL) present
      inside the core and the core-shell interface along with cationic head groups.
      This is further supported by monitoring interaction between ILs and polymer
      micelle using (1)H NMR spectroscopy. The results are discussed and explained as a
      function of concentration of C8PyCl, alkyl chain length, and anions of N
      alkylpyridinium halides. 

PMID- 25380312
TI  - Lis1 regulates dynein by sterically blocking its mechanochemical cycle.
AB  - Regulation of cytoplasmic dynein's motor activity is essential for diverse
      eukaryotic functions, including cell division, intracellular transport, and brain
      development. The dynein regulator Lis1 is known to keep dynein bound to
      microtubules; however, how this is accomplished mechanistically remains unknown.
      We have used three-dimensional electron microscopy, single-molecule imaging,
      biochemistry, and in vivo assays to help establish this mechanism. The three
      dimensional structure of the dynein-Lis1 complex shows that binding of Lis1 to
      dynein's AAA+ ring sterically prevents dynein's main mechanical element, the
      'linker', from completing its normal conformational cycle. Single-molecule
      experiments show that eliminating this block by shortening the linker to a point
      where it can physically bypass Lis1 renders single dynein motors insensitive to
      regulation by Lis1. Our data reveal that Lis1 keeps dynein in a persistent
      microtubule-bound state by directly blocking the progression of its
      mechanochemical cycle. 

PMID- 25380315
TI  - A novel approach of dynamic cross correlation analysis on molecular dynamics
      simulations and its application to Ets1 dimer-DNA complex.
AB  - The dynamic cross correlation (DCC) analysis is a popular method for analyzing
      the trajectories of molecular dynamics (MD) simulations. However, it is difficult
      to detect correlative motions that appear transiently in only a part of the
      trajectory, such as atomic contacts between the side-chains of amino acids, which
      may rapidly flip. In order to capture these multi-modal behaviors of atoms, which
      often play essential roles, particularly at the interfaces of macromolecules, we
      have developed the "multi-modal DCC (mDCC)" analysis. The mDCC is an extension of
      the DCC and it takes advantage of a Bayesian-based pattern recognition technique.
      We performed MD simulations for molecular systems modeled from the (Ets1)2-DNA
      complex and analyzed their results with the mDCC method. Ets1 is an essential
      transcription factor for a variety of physiological processes, such as immunity
      and cancer development. Although many structural and biochemical studies have so
      far been performed, its DNA binding properties are still not well characterized.
      In particular, it is not straightforward to understand the molecular mechanisms
      how the cooperative binding of two Ets1 molecules facilitates their recognition
      of Stromelysin-1 gene regulatory elements. A correlation network was constructed
      among the essential atomic contacts, and the two major pathways by which the two
      Ets1 molecules communicate were identified. One is a pathway via direct protein
      protein interactions and the other is that via the bound DNA intervening two
      recognition helices. These two pathways intersected at the particular cytosine
      bases (C110/C11), interacting with the H1, H2, and H3 helices. Furthermore, the
      mDCC analysis showed that both pathways included the transient interactions at
      their intermolecular interfaces of Tyr396-C11 and Ala327-Asn380 in multi-modal
      motions of the amino acid side chains and the nucleotide backbone. Thus, the
      current mDCC approach is a powerful tool to reveal these complicated behaviors
      and scrutinize intermolecular communications in a molecular system. 

PMID- 25380317
TI  - Molecular dynamics simulations reveal a dielectric-responsive coronal structure
      in protein-polymer surfactant hybrid nanoconstructs.
AB  - Solvent-free liquid proteins are a new class of thermally stable hybrid
      bionanomaterials that are produced by extensive lyophilization of aqueous
      solutions of protein-polymer surfactant nanoconjugates followed by thermal
      annealing. The hybrid constructs, which consist of a globular protein core
      surrounded by a monolayer of electrostatically coupled polymer surfactant
      molecules, exhibit nativelike structure, function, and backbone dynamics over a
      large temperature range. Despite the key importance of the polymer surfactant
      shell, very little is known about the atomistic structure of the corona and how
      it influences the phase behavior and properties of these novel nanoscale objects.
      Here we present molecular dynamics simulations of protein-polymer surfactant
      nanoconjugates consisting of globular cores of myoglobin or lysozyme and
      demonstrate that the derived structural parameters are highly consistent with
      experimental values. We show that the coronal layer structure is responsive to
      the dielectric constant of the medium and that the mobility of the polymer
      surfactant molecules is significantly hindered in the solvent-free state,
      providing a basis for the origins of retained protein dynamics in these novel
      biofluids. Taken together, our results suggest that the extension of molecular
      dynamics simulations to hybrid nanoscale objects could be of generic value in
      diverse areas of soft matter chemistry, bioinspired engineering, and biomolecular
      nanotechnology. 

PMID- 25380318
TI  - Do physiological scoring and a novel point of care metabolic screen predict 48-h
      outcome in admissions from the emergency department resuscitation area?
AB  - OBJECTIVE: We aimed to compare the performance of a widely used physiological
      score [Modified Early Warning Score (MEWS)] and a novel metabolic score (derived
      from a blood gas) in predicting outcome in emergency department patients. DESIGN,
      SETTING AND PARTICIPANTS: We carried out a prospective observational study using
      a convenience sample of 200 patients presenting to the resuscitation area of an
      inner-city teaching hospital over 4 months. MAIN OUTCOME MEASURES: We looked
      primarily at whether either score predicted new organ failure at 48 h. Our
      secondary outcome measures were escalation of care and mortality at 48 h.
      RESULTS: In univariate analysis, MEWS and the metabolic score predicted 48-h
      organ failure [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.04-1.35,
      P=0.009, and OR 1.34, 95% CI 1.015-1.56, P<0.001, respectively]. Both MEWS and
      the metabolic score predicted 48-h death (OR 1.32, 95% CI 1.02-1.71, P=0.03, and
      OR 1.56, 95% CI 1.18-2.06, P=0.002, respectively) in univariate analysis. Neither
      predicted 48-h escalation of care. The metabolic score remained statistically
      significant at predicting organ failure or death after controlling for MEWS
      parameters (OR 1.35, 95% CI 1.13-1.62, P=0.001, and OR 1.74, 95% CI 1.13-2.69,
      P=0.01, respectively). In contrast, MEWS was no longer associated with these
      outcomes; however, our study has small participant numbers. CONCLUSION: This
      pilot data suggest that a blood gas-derived metabolic score on emergency
      department arrival may be superior to MEWS at predicting organ failure and death
      at 48 h.

PMID- 25380319
TI  - Self-referrals in a Dutch Emergency Department: how appropriate are they?
AB  - OBJECTIVE: Self-referred visits account for an average of 30% of all Emergency
      Department (ED) visits in the Netherlands. Some of these are considered
      inappropriate, because patients receive care that a GP can provide. Worldwide,
      studies have used various methods to determine the proportion of inappropriate
      visits by self-referred patients, resulting in diverging percentages. The aim of
      this study was to find a reliable percentage of appropriate visits to the ED by
      self-referred patients in the Netherlands. METHODS: This observational,
      prospective study was performed in the ED of a hospital in the Netherlands. Data
      were collected on all self-referred patients in four separate months over 1 year.
      The appropriateness of an ED visit was determined at two time points: first,
      after primary assessment of the patient, using predefined criteria, and second
      the moment the patient left the ED, on the basis of the diagnosis and treatment
      received. Finally, the perspective of the patients was taken into account using a
      questionnaire. RESULTS: In 4 months 3196 self-referred patients were included. In
      all, 1862 (58.8%) visits were classified as appropriate according to the
      predefined criteria. When the second time point was taken into consideration,
      48.1% of the patients had a secondary care diagnosis and/or needed secondary care
      treatment, classifying their visits as appropriate. According to the opinion of
      the patients 76.7% classified their visit as appropriate. CONCLUSION: The
      percentage of appropriate ED visits by self-referred patients in the Netherlands
      ranges from 48.1 to 58.8%, as determined using two different methods.

PMID- 25380321
TI  - Clinical and genomic characterization of two patients with a duplication of 9q34:
      comparison and review of the literature.

PMID- 25380322
TI  - Branchiootorenal syndrome with skeletal defects: a novel association in a Mexican
      child.

PMID- 25380324
TI  - Solution-processed field-effect transistors based on dihexylquaterthiophene films
      with performances exceeding those of vacuum-sublimed films.
AB  - Solution-processable oligothiophenes are model systems for charge transport and
      fabrication of organic field-effect transistors (OFET) . Herein we report a
      structure vs function relationship study focused on the electrical
      characteristics of solution-processed dihexylquaterthiophene (DH4T)-based OFET.
      We show that by combining the tailoring of all interfaces in the bottom-contact
      bottom-gate transistor, via chemisorption of ad hoc molecules on electrodes and
      dielectric, with suitable choice of the film preparation conditions (including
      solvent type, concentration, volume, and deposition method), it is possible to
      fabricate devices exhibiting field-effect mobilities exceeding those of vacuum
      processed DH4T transistors. In particular, the evaporation rate of the solvent,
      the processing temperature, as well as the concentration of the semiconducting
      material were found to hold a paramount importance in driving the self-assembly
      toward the formation of highly ordered and low-dimensional supramolecular
      architectures, confirming the kinetically governed nature of the self-assembly
      process. Among the various architectures, hundreds-of-micrometers long and thin
      DH4T crystallites exhibited enhanced charge transport.

PMID- 25380325
TI  - The structure of insulin at the air/water interface: monomers or dimers?
AB  - The hydrophobic character of the air/water interface affects the oligomeric
      composition of insulin. By using interface-specific vibrational sum frequency
      spectroscopy and calculations of insulin monomer and dimer second-order nonlinear
      susceptibilities chi((2)), we show that insulin monomers segregate to the
      air/water interface. 

PMID- 25380323
TI  - Temporal trends in the inflammatory cytokine profile of human breastmilk.
AB  - A longer lifetime duration of breastfeeding may decrease the risk of breast
      cancer by reducing breast inflammation and mitigating inflammatory cytokine
      expression during postlactational involution. However, little is known about how
      the inflammatory cytokine profile in human breastmilk changes over time. To study
      temporal trends in breastmilk cytokine expression, we measured 80 human cytokines
      in the whey fraction of breastmilk samples from 15 mothers at 1, 4, 8, and 12
      weeks postpartum. We used mixed models to identify temporal changes in cytokine
      expression and investigated parity status (multiparous vs. primiparous) as a
      potential confounder. Nine cytokines (monocyte chemoattractant protein-1,
      epithelial-derived neutrophil-activating protein-78, hepatocyte growth factor,
      insulin-like growth factor-binding protein-1, interleukin-16, interleukin-8,
      macrophage colony-stimulating factor, osteoprotegerin, and tissue inhibitor of
      metallopeptidase-2) had significantly decreased expression with increasing
      breastfeeding duration; all nine have known roles in breast involution,
      inflammation, and cancer and may serve as biomarkers of changing breast
      microenvironment. No cytokine significantly increased in level over the study
      period. Total protein concentration significantly decreased over time (p<0.0001),
      which may mediate the association between length of breastfeeding and
      inflammatory cytokine expression. Parity status did not confound temporal trends,
      but levels of several cytokines were significantly higher among multiparous
      versus primiparous women. Our results suggest that inflammatory cytokine
      expression during lactation is dynamic, and expressed milk may provide a
      noninvasive window into the extensive biological changes that occur in the
      postpartum breast.

PMID- 25380327
TI  - A large-scale superhydrophobic surface-enhanced Raman scattering (SERS) platform
      fabricated via capillary force lithography and assembly of Ag nanocubes for
      ultratrace molecular sensing.
AB  - An analytical platform with an ultratrace detection limit in the atto-molar (aM)
      concentration range is vital for forensic, industrial and environmental sectors
      that handle scarce/highly toxic samples. Superhydrophobic surface-enhanced Raman
      scattering (SERS) platforms serve as ideal platforms to enhance detection
      sensitivity by reducing the random spreading of aqueous solution. However, the
      fabrication of superhydrophobic SERS platforms is generally limited due to the
      use of sophisticated and expensive protocols and/or suffers structural and signal
      inconsistency. Herein, we demonstrate a high-throughput fabrication of a stable
      and uniform superhydrophobic SERS platform for ultratrace molecular sensing.
      Large-area box-like micropatterns of the polymeric surface are first fabricated
      using capillary force lithography (CFL). Subsequently, plasmonic properties are
      incorporated into the patterned surfaces by decorating with Ag nanocubes using
      the Langmuir-Schaefer technique. To create a stable superhydrophobic SERS
      platform, an additional 25 nm Ag film is coated over the Ag nanocube-decorated
      patterned template followed by chemical functionalization with
      perfluorodecanethiol. Our resulting superhydrophobic SERS platform demonstrates
      excellent water-repellency with a static contact angle of 165 degrees  +/- 9
      degrees  and a consequent analyte concentration factor of 59-fold, as compared to
      its hydrophilic counterpart. By combining the analyte concentration effect of
      superhydrophobic surfaces with the intense electromagnetic "hot spots" of Ag
      nanocubes, our superhydrophobic SERS platform achieves an ultra-low detection
      limit of 10(-17) M (10 aM) for rhodamine 6G using just 4 MUL of analyte
      solutions, corresponding to an analytical SERS enhancement factor of 10(13). Our
      fabrication protocol demonstrates a simple, cost- and time-effective approach for
      the large-scale fabrication of a superhydrophobic SERS platform for ultratrace
      molecular detection. 

PMID- 25380326
TI  - Endovascular therapy by CO2 angiography to prevent contrast-induced nephropathy
      in patients with chronic kidney disease: a prospective multicenter trial of CO2
      angiography registry.
AB  - OBJECTIVES: To assess the safety and efficacy of carbon dioxide (CO2) angiography
      guided endovascular therapy (EVT) for renal, iliofemoral artery disease.
      BACKGROUND: Patients with peripheral vascular disease (PVD) often have chronic
      kidney disease (CKD) and the use of iodinated contrast media may enhance the risk
      of contrast-induced nephropathy (CIN). Contrast volume reduction is an effective
      CIN preventive strategy. METHODS: A prospective multicenter registry was
      developed and six clinical centers participated in the study. Patients with an
      estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 and stage-3 CKD
      were recruited between February 2012 and March 2013. CO2 angiography-guided EVT
      was performed; incomplete CO2 angiograms were supplemented by intravascular
      ultrasound, pressure wire, and/or minimal iodinated contrast media. The primary
      endpoint was a composite of freedom from renal events and freedom from major CO2
      angiography related complications. RESULTS: This study included 98 patients with
      109 lesions. The mean eGFR baseline was 35.2+/-12.7 ml min(-1). CO2 angiography
      guided angioplasty were performed in 16 renal arteries, 31 aortoiliac arteries,
      and 62 superficial femoral arteries. The technical success rate was 97.9%.
      Average CO2 consumption was 281.4+/-155.8 ml, average dose of iodinated contrast
      media was 15.0+/-18.1 ml. Primary endpoint was 92.8% (91/98). Incidence of CIN
      was 5.1% (5/98) and CO2 angiography-related complications occurred in 17.3%
      (17/98). Two cases (2%) developed severe, fatal, nonocclusive mesenteric ischemia
      (NOMI). CONCLUSIONS: This trial showed that CO2 angiography-guided angioplasty
      was effective for preventing CIN, however, CO2 angiography related complication
      was somewhat high.

PMID- 25380329
TI  - Micromagnetism of permalloy antidot arrays prepared from alumina templates.
AB  - Magnetic hysteresis processes of hexagonal arrays of permalloy antidots have been
      studied by means of micromagnetic simulations as a function of geometrical
      parameters. The ideal system shows a maximum of the coercive field as a function
      of the antidot diameter. The simulated magnetic behavior has been compared with
      experimental values for antidot arrays of permalloy prepared from alumina
      templates with thicknesses between 2 and 60 nm, showing a monotonic increase of
      the coercive field as a function of the antidot diameter. We show that the
      introduction into simulations of the combination of variable antidot diameters
      from bottom to top due to the fabrication process and, more importantly, large
      geometrical domains, which break the sample symmetry, solves the discrepancy
      between the simulations and the experiment. 

PMID- 25380328
TI  - Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4
      based dissection of protocerebral bridge neurons and circuits.
AB  - Insects exhibit an elaborate repertoire of behaviors in response to environmental
      stimuli. The central complex plays a key role in combining various modalities of
      sensory information with an insect's internal state and past experience to select
      appropriate responses. Progress has been made in understanding the broad spectrum
      of outputs from the central complex neuropils and circuits involved in numerous
      behaviors. Many resident neurons have also been identified. However, the specific
      roles of these intricate structures and the functional connections between them
      remain largely obscure. Significant gains rely on obtaining a comprehensive
      catalog of the neurons and associated GAL4 lines that arborize within these brain
      regions, and on mapping neuronal pathways connecting these structures. To this
      end, small populations of neurons in the Drosophila melanogaster central complex
      were stochastically labeled using the multicolor flip-out technique and a catalog
      was created of the neurons, their morphologies, trajectories, relative
      arrangements, and corresponding GAL4 lines. This report focuses on one structure
      of the central complex, the protocerebral bridge, and identifies just 17
      morphologically distinct cell types that arborize in this structure. This work
      also provides new insights into the anatomical structure of the four components
      of the central complex and its accessory neuropils. Most strikingly, we found
      that the protocerebral bridge contains 18 glomeruli, not 16, as previously
      believed. Revised wiring diagrams that take into account this updated
      architectural design are presented. This updated map of the Drosophila central
      complex will facilitate a deeper behavioral and physiological dissection of this
      sophisticated set of structures.

PMID- 25380330
TI  - A bioinspired polymer-bound Mn-porphyrin as an artificial active center of
      catalase.
AB  - The complex comprising a cationic Mn-porphyrin and carboxymethyl poly(1
      vinylimidazole) (CM-PVIm) was prepared as an artificial active center of
      catalase. Interestingly, the catalase activity of the complex depends on the
      chain length of the polymer and the chemical structure of Mn-porphyrin. This
      study is one step forward in the development of a new class of water-soluble
      catalase mimics. 

PMID- 25380331
TI  - Dynamics of gamma bursts in local field potentials.
AB  - In this letter, we provide a stochastic analysis of, and supporting simulation
      data for, a stochastic model of the generation of gamma bursts in local field
      potential (LFP) recordings by interacting populations of excitatory and
      inhibitory neurons. Our interest is in behavior near a fixed point of the
      stochastic dynamics of the model. We apply a recent limit theorem of stochastic
      dynamics to probe into details of this local behavior, obtaining several new
      results. We show that the stochastic model can be written in terms of a rotation
      multiplied by a two-dimensional standard Ornstein-Uhlenbeck (OU) process. Viewing
      the rewritten process in terms of phase and amplitude processes, we are able to
      proceed further in analysis. We demonstrate that gamma bursts arise in the model
      as excursions of the modulus of the OU process. The associated pair of stochastic
      phase and amplitude processes satisfies their own pair of stochastic differential
      equations, which indicates that large phase slips occur between gamma bursts.
      This behavior is mirrored in LFP data simulated from the original model. These
      results suggest that the rewritten model is a valid representation of the
      behavior near the fixed point for a wide class of models of oscillatory neural
      processes. 

PMID- 25380332
TI  - Natural gradient learning algorithms for RBF networks.
AB  - Radial basis function (RBF) networks are one of the most widely used models for
      function approximation and classification. There are many strange behaviors in
      the learning process of RBF networks, such as slow learning speed and the
      existence of the plateaus. The natural gradient learning method can overcome
      these disadvantages effectively. It can accelerate the dynamics of learning and
      avoid plateaus. In this letter, we assume that the probability density function
      (pdf) of the input and the activation function are gaussian. First, we introduce
      natural gradient learning to the RBF networks and give the explicit forms of the
      Fisher information matrix and its inverse. Second, since it is difficult to
      calculate the Fisher information matrix and its inverse when the numbers of the
      hidden units and the dimensions of the input are large, we introduce the adaptive
      method to the natural gradient learning algorithms. Finally, we give an explicit
      form of the adaptive natural gradient learning algorithm and compare it to the
      conventional gradient descent method. Simulations show that the proposed adaptive
      natural gradient method, which can avoid the plateaus effectively, has a good
      performance when RBF networks are used for nonlinear functions approximation. 

PMID- 25380333
TI  - Toward a multisubject analysis of neural connectivity.
AB  - Directed acyclic graphs (DAGs) and associated probability models are widely used
      to model neural connectivity and communication channels. In many experiments,
      data are collected from multiple subjects whose connectivities may differ but are
      likely to share many features. In such circumstances, it is natural to leverage
      similarity among subjects to improve statistical efficiency. The first exact
      algorithm for estimation of multiple related DAGs was recently proposed by Oates,
      Smith, Mukherjee, and Cussens ( 2014 ). In this letter we present examples and
      discuss implications of the methodology as applied to the analysis of fMRI data
      from a multisubject experiment. Elicitation of tuning parameters requires care,
      and we illustrate how this may proceed retrospectively based on technical
      replicate data. In addition to joint learning of subject-specific connectivity,
      we allow for heterogeneous collections of subjects and simultaneously estimate
      relationships between the subjects themselves. This letter aims to highlight the
      potential for exact estimation in the multisubject setting. 

PMID- 25380334
TI  - Graph degree sequence solely determines the expected hopfield network pattern
      stability.
AB  - We analyze the effect of network topology on the pattern stability of the
      Hopfield neural network in the case of general graphs. The patterns are randomly
      selected from a uniform distribution. We start the Hopfield procedure from some
      pattern v. An error in an entry e of v is the situation where, if the procedure
      is started at e, the value of e flips. Such an entry is an instability point.
      Note that we disregard the value at e by the end of the procedure, as well as
      what happens if we start the procedure from another pattern v' or another entry
      e' of v. We measure the instability of the system by the expected total number of
      instability points of all the patterns. Our main result is that the instability
      of the system does not depend on the exact topology of the underlying graph, but
      rather only on its degree sequence. Moreover, for a large number of nodes, the
      instability can be approximated by mSigmani=1(1 - Phi(?deltai/m-1)), where is the
      standard normal distribution function and delta1, . . . , deltan are the degrees
      of the nodes.

PMID- 25380336
TI  - Optimizing the representation of orientation preference maps in visual cortex.
AB  - The colorful representation of orientation preference maps in primary visual
      cortex has become iconic. However, the standard representation is misleading
      because it uses a color mapping to indicate orientations based on the HSV (hue,
      saturation, value) color space, for which important perceptual features such as
      brightness, and not just hue, vary among orientations. This means that some
      orientations stand out more than others, conveying a distorted visual impression.
      This is particularly problematic for visualizing subtle biases caused by slight
      overrepresentation of some orientations due to, for example, stripe rearing. We
      show that displaying orientation maps with a color mapping based on a slightly
      modified version of the HCL (hue, chroma, lightness) color space, so that
      primarily only hue varies between orientations, leads to a more balanced visual
      impression. This makes it easier to perceive the true structure of this seminal
      example of functional brain architecture. 

PMID- 25380335
TI  - Spike train SIMilarity Space (SSIMS): a framework for single neuron and ensemble
      data analysis.
AB  - Increased emphasis on circuit level activity in the brain makes it necessary to
      have methods to visualize and evaluate large-scale ensemble activity beyond that
      revealed by raster-histograms or pairwise correlations. We present a method to
      evaluate the relative similarity of neural spiking patterns by combining spike
      train distance metrics with dimensionality reduction. Spike train distance
      metrics provide an estimate of similarity between activity patterns at multiple
      temporal resolutions. Vectors of pair-wise distances are used to represent the
      intrinsic relationships between multiple activity patterns at the level of single
      units or neuronal ensembles. Dimensionality reduction is then used to project the
      data into concise representations suitable for clustering analysis as well as
      exploratory visualization. Algorithm performance and robustness are evaluated
      using multielectrode ensemble activity data recorded in behaving primates. We
      demonstrate how spike train SIMilarity space (SSIMS) analysis captures the
      relationship between goal directions for an eight-directional reaching task and
      successfully segregates grasp types in a 3D grasping task in the absence of
      kinematic information. The algorithm enables exploration of virtually any type of
      neural spiking (time series) data, providing similarity-based clustering of
      neural activity states with minimal assumptions about potential information
      encoding models. 

PMID- 25380337
TI  - Using multilayer perceptron computation to discover ideal insect olfactory
      receptor combinations in the mosquito and fruit fly for an efficient electronic
      nose.
AB  - The model organism, Drosophila melanogaster, and the mosquito Anopheles gambiae
      use 60 and 79 odorant receptors, respectively, to sense their olfactory world.
      However, a commercial "electronic nose" in the form of an insect olfactory
      biosensor demands very low numbers of receptors at its front end of detection due
      to the difficulties of receptor/sensor integration and functionalization. In this
      letter, we demonstrate how computation via artificial neural networks (ANNs), in
      the form of multilayer perceptrons (MLPs), can be successfully incorporated as
      the signal processing back end of the biosensor to drastically reduce the number
      of receptors to three while still retaining 100% performance of odorant detection
      to that of a full complement of receptors. In addition, we provide a detailed
      performance comparison between D. melanogaster and A. gambiae odorant receptors
      and demonstrate that A. gambiae receptors provide superior olfaction detection
      performance over D. melanogaster for very low receptor numbers. The results from
      this study present the possibility of using the computation of MLPs to discover
      ideal biological olfactory receptors for an olfactory biosensor device to provide
      maximum classification performance of unknown odorants. 

PMID- 25380338
TI  - Foundations of support constraint machines.
AB  - The mathematical foundations of a new theory for the design of intelligent agents
      are presented. The proposed learning paradigm is centered around the concept of
      constraint, representing the interactions with the environment, and the parsimony
      principle. The classical regularization framework of kernel machines is naturally
      extended to the case in which the agents interact with a richer environment,
      where abstract granules of knowledge, compactly described by different linguistic
      formalisms, can be translated into the unified notion of constraint for defining
      the hypothesis set. Constrained variational calculus is exploited to derive
      general representation theorems that provide a description of the optimal body of
      the agent (i.e., the functional structure of the optimal solution to the learning
      problem), which is the basis for devising new learning algorithms. We show that
      regardless of the kind of constraints, the optimal body of the agent is a support
      constraint machine (SCM) based on representer theorems that extend classical
      results for kernel machines and provide new representations. In a sense, the
      expressiveness of constraints yields a semantic-based regularization theory,
      which strongly restricts the hypothesis set of classical regularization. Some
      guidelines to unify continuous and discrete computational mechanisms are given so
      as to accommodate in the same framework various kinds of stimuli, for example,
      supervised examples and logic predicates. The proposed view of learning from
      constraints incorporates classical learning from examples and extends naturally
      to the case in which the examples are subsets of the input space, which is
      related to learning propositional logic clauses. 

PMID- 25380340
TI  - Conditional density estimation with dimensionality reduction via squared-loss
      conditional entropy minimization.
AB  - Regression aims at estimating the conditional mean of output given input.
      However, regression is not informative enough if the conditional density is
      multimodal, heteroskedastic, and asymmetric. In such a case, estimating the
      conditional density itself is preferable, but conditional density estimation
      (CDE) is challenging in high-dimensional space. A naive approach to coping with
      high dimensionality is to first perform dimensionality reduction (DR) and then
      execute CDE. However, a two-step process does not perform well in practice
      because the error incurred in the first DR step can be magnified in the second
      CDE step. In this letter, we propose a novel single-shot procedure that performs
      CDE and DR simultaneously in an integrated way. Our key idea is to formulate DR
      as the problem of minimizing a squared-loss variant of conditional entropy, and
      this is solved using CDE. Thus, an additional CDE step is not needed after DR. We
      demonstrate the usefulness of the proposed method through extensive experiments
      on various data sets, including humanoid robot transition and computer art. 

PMID- 25380339
TI  - Spatiotemporal conditional inference and hypothesis tests for neural ensemble
      spiking precision.
AB  - The collective dynamics of neural ensembles create complex spike patterns with
      many spatial and temporal scales. Understanding the statistical structure of
      these patterns can help resolve fundamental questions about neural computation
      and neural dynamics. Spatiotemporal conditional inference (STCI) is introduced
      here as a semiparametric statistical framework for investigating the nature of
      precise spiking patterns from collections of neurons that is robust to
      arbitrarily complex and nonstationary coarse spiking dynamics. The main idea is
      to focus statistical modeling and inference not on the full distribution of the
      data, but rather on families of conditional distributions of precise spiking
      given different types of coarse spiking. The framework is then used to develop
      families of hypothesis tests for probing the spatiotemporal precision of spiking
      patterns. Relationships among different conditional distributions are used to
      improve multiple hypothesis-testing adjustments and design novel Monte Carlo
      spike resampling algorithms. Of special note are algorithms that can locally
      jitter spike times while still preserving the instantaneous peristimulus time
      histogram or the instantaneous total spike count from a group of recorded
      neurons. The framework can also be used to test whether first-order maximum
      entropy models with possibly random and time-varying parameters can account for
      observed patterns of spiking. STCI provides a detailed example of the generic
      principle of conditional inference, which may be applicable to other areas of
      neurostatistical analysis. 

PMID- 25380341
TI  - Efficient training of convolutional deep belief networks in the frequency domain
      for application to high-resolution 2D and 3D images.
AB  - Deep learning has traditionally been computationally expensive, and advances in
      training methods have been the prerequisite for improving its efficiency in order
      to expand its application to a variety of image classification problems. In this
      letter, we address the problem of efficient training of convolutional deep belief
      networks by learning the weights in the frequency domain, which eliminates the
      time-consuming calculation of convolutions. An essential consideration in the
      design of the algorithm is to minimize the number of transformations to and from
      frequency space. We have evaluated the running time improvements using two
      standard benchmark data sets, showing a speed-up of up to 8 times on 2D images
      and up to 200 times on 3D volumes. Our training algorithm makes training of
      convolutional deep belief networks on 3D medical images with a resolution of up
      to 128*128*128 voxels practical, which opens new directions for using deep
      learning for medical image analysis.

PMID- 25380342
TI  - Concept for simultaneous and specific in situ monitoring of amyloid oligomers and
      fibrils via Forster resonance energy transfer.
AB  - Oligomeric species of amyloidogenic peptides or proteins are often considered as
      the most toxic species in several amyloid disorders, like Alzheimer or
      Parkinson's diseases, and hence came into the focus of research interest and as a
      therapeutic target. An easy and specific monitoring of oligomeric species would
      be of high utility in the field, as it is the case for thioflavin T fluorescence
      for the fibrillar aggregates. Here, we show proof of concept for a new sensitive
      method to increase specific detection of oligomers by two extrinsic fluorophores.
      This is achieved by exploiting a Forster resonance energy transfer (FRET) between
      the two fluorophores. Thus, a mixture of two extrinsic fluorophores, bis-ANS and
      a styrylquinoxalin derivative, enabled one to monitor simultaneously and in situ
      the presence of oligomers and fibrils of amyloidogenic peptides. Thereby, the
      formation of oligomers and their transformation into fibrils can be followed. 

PMID- 25380343
TI  - Pressure dependence of butyl nitrate formation in the reaction of butylperoxy
      radicals with nitrogen oxide.
AB  - The yield of 1- and 2-butyl nitrates in the gas-phase reactions of NO with n
      C4H9O2 and sec-C4H9O2, obtained from the reaction of F atoms with n-butane in the
      presence of O2, was determined over the pressure range of 100-600 Torr at 298 K
      using a high-pressure turbulent flow reactor coupled with a chemical ionization
      quadrupole mass spectrometer. The yield of butyl nitrates was found to increase
      linearly with pressure from about 3% at 100 Torr to about 8% at 600 Torr. The
      results obtained are compared with the available data concerning nitrate
      formation from NO reaction with other small alkylperoxy radicals. These results
      are also discussed through the topology of the lowest potential energy surface
      mainly obtained from DFT(B3LYP/aug-cc-pVDZ) calculations of the RO2 + NO reaction
      paths. The formation of alkyl nitrates, due essentially to collision processes,
      is analyzed through a model that points out the pertinent physical parameters of
      this system. 

PMID- 25380344
TI  - The effectiveness of propolis on gingivitis: a randomized controlled trial.
AB  - BACKGROUND: A randomized, double-blind, controlled clinical trial was conducted
      to evaluate the effectiveness of a propolis rinse on induced gingivitis by using
      the co-twin study design. METHODS: Twenty-one twin pairs (n=42) were enrolled in
      a gingivitis study with oral hygiene promotion (14 days) and gingivitis induction
      (21 days). During the gingivitis induction phase, one member of the twin pair was
      randomly assigned to a 2% typified propolis rinse, and the other was assigned a
      color-matched 0.05% sodium fluoride plus 0.05% cetylpyridinium chloride rinse
      (positive control). Patients rinsed twice daily with 20 mL for 30 seconds for 21
      days. Gingivitis was measured on days -14 (baseline), 0 (after hygiene phase),
      and 21 (after no-hygiene phase) by using the Papillary Bleeding Score (PBS) and
      by standard digital imaging of the gum tissues (G-parameter). RESULTS: The 38
      persons who completed the study (age 13-22 years) were well balanced according to
      PBS at baseline and G-parameter after the initial hygiene phase. After 21 days
      without oral hygiene, the propolis rinse and positive control rinse groups did
      not differ significantly for average PBS measurements or G-parameter.
      CONCLUSIONS: Use of a 2% typified propolis rinse was equivalent to a positive
      control rinse during a 21-day no-hygiene period.

PMID- 25380346
TI  - In response to the comments to the paper 'Modelling of cell killing due to
      sparsely ionizing radiation in normoxic and hypoxic conditions and an extension
      to high LET radiation' by T. Friedrich et al.

PMID- 25380345
TI  - Rosmarinic acid exerts an antiosteoporotic effect in the RANKL-induced mouse
      model of bone loss by promotion of osteoblastic differentiation and inhibition of
      osteoclastic differentiation.
AB  - SCOPE: Bone homeostasis is ensured by the balance between bone formation and
      resorption. Thus, control of the recruitment, proliferation, and differentiation
      of bone cells is essential to maintain bone mass. The aim of this study was to
      elucidate the effects of rosmarinic acid as a potential therapeutic agent on bone
      metabolism using bone cells and a mouse model. METHODS AND RESULTS: Rosmarinic
      acid increased alkaline phosphatase activity and induced mineralization in
      osteoblasts. Addition of rosmarinic acid to cultures of calvarial osteoblastic
      cells prepared from T-cell factor/beta-catenin TOP-GAL mutant mice strongly
      induced the expression of LacZ and promoted stabilization of beta-catenin in the
      cytoplasm of ST2 cells, suggesting that rosmarinic acid affects the canonical Wnt
      signaling pathway. Moreover, rosmarinic acid inhibited not only osteoclast
      formation in cocultures of mouse bone marrow cells and osteoblasts, but also
      receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastic
      differentiation in bone marrow-derived macrophages. RANKL-induced p38 mitogen
      activated protein kinase and the expression of nuclear factor of activated T
      cell, c-Jun, and c-Fos were inhibited by rosmarinic acid in bone marrow
      macrophages. Finally, we confirmed that rosmarinic acid improved bone mass in a
      soluble RANKL-induced bone loss mouse model. CONCLUSION: Rosmarinic acid has dual
      regulatory effects on bone metabolism and may control the bone functions by
      controlling osteoblastic and osteoclastic differentiation.

PMID- 25380348
TI  - Effects of stratospheric ozone depletion, solar UV radiation, and climate change
      on biogeochemical cycling: interactions and feedbacks.
AB  - Climate change modulates the effects of solar UV radiation on biogeochemical
      cycles in terrestrial and aquatic ecosystems, particularly for carbon cycling,
      resulting in UV-mediated positive or negative feedbacks on climate. Possible
      positive feedbacks discussed in this assessment include: (i) enhanced UV-induced
      mineralisation of above ground litter due to aridification; (ii) enhanced UV
      induced mineralisation of photoreactive dissolved organic matter (DOM) in aquatic
      ecosystems due to changes in continental runoff and ice melting; (iii) reduced
      efficiency of the biological pump due to UV-induced bleaching of coloured
      dissolved organic matter (CDOM) in stratified aquatic ecosystems, where CDOM
      protects phytoplankton from the damaging solar UV-B radiation. Mineralisation of
      organic matter results in the production and release of CO2, whereas the
      biological pump is the main biological process for CO2 removal by aquatic
      ecosystems. This paper also assesses the interactive effects of solar UV
      radiation and climate change on the biogeochemical cycling of aerosols and trace
      gases other than CO2, as well as of chemical and biological contaminants.
      Interacting effects of solar UV radiation and climate change on biogeochemical
      cycles are particularly pronounced at terrestrial-aquatic interfaces. 

PMID- 25380347
TI  - Preliminary associations between childhood neglect, MIF, and cortisol: potential
      pathways to long-term disease risk.
AB  - The study examined Hypothalamus-Pituitary-Adrenal (HPA) axis and inflammatory
      signaling in 206 youth with histories of prenatal drug exposure and self-reported
      histories of maltreatment. Youth with histories of severe neglect showed elevated
      levels of cortisol, the end product of the HPA axis, in comparison to youth with
      lower or minimal levels of neglect. Histories of severe neglect also were
      associated with increased levels of Macrophage Migration Inhibitory Factor (MIF),
      a cytokine known to be intricately involved in HPA axis regulation. Salivary MIF
      levels also were positively associated with youth age and prenatal drug exposure.
      These MIF and cortisol alterations may signal pathophysiological disruptions in
      the neuro-endocrine and immune systems, which may lead to trajectories of
      increased disease risk among vulnerable youth. Our findings also provide
      preliminary support for the validity and reliability of a noninvasive salivary
      assessment of MIF.

PMID- 25380349
TI  - Detection and biological activities of carboxyethylpyrrole ethanolamine
      phospholipids (CEP-EPs).
AB  - Oxidation of docosahexaenoate phospholipids produces 4-hydroxy-7-oxo-hept-5-eonyl
      phospholipids (HOHA-PLs) that react with protein lysyl epsilon-amino residues to
      generate 2-omega-carboxyethylpyrrole (CEP) derivatives, endogenous factors that
      induce angiogenesis in the retina and tumors. It seemed likely, but remained
      unproven, that HOHA-PLs react with ethanolamine phospholipids (EPs) in vivo to
      generate CEP-EPs. We now show that CEP-EPs are present in human blood at 4.6-fold
      higher levels in age-related macular degeneration plasma than in normal plasma.
      We also show that CEP-EPs are pro-angiogenic, inducing tube formation by human
      umbilical vein endothelial cells by activating Toll-like receptor 2. CEP-EP
      levels may be a useful biomarker for clinical assessment of AMD risk and CEP
      associated tumor progression and a tool for monitoring the efficacy of
      therapeutic interventions.

PMID- 25380352
TI  - Molecular dynamics simulation of thermal ripples in graphene with bond-order
      informed harmonic constraints.
AB  - We describe the results of atomistic molecular dynamics simulations of thermal
      rippling in graphene with the use of a generic harmonic constraint model. The
      distance and angular constraint constants are calculated directly from the second
      generation bond-order interatomic potential that describes carbon binding in
      graphene. We quantify the thermal rippling process in detail by calculating the
      overall rippling averages, the normal-normal correlation distributions and the
      height distributions. In addition, we consider the effect of a dihedral angular
      constraint, as well as the effect of sample size on the simulated rippling
      averages. The dynamic corrugation morphologies of simulated graphene samples
      obtained with the harmonic constraint model at various temperatures are, overall,
      consistent with those obtained with the bond-order potential and are in
      qualitative accord with previously reported findings. Given the wide availability
      of the harmonic constraint model in various molecular mechanics implementations,
      along with its high computational efficiency, our results indicate a possible use
      for the presented model in multicomponent dynamic simulations, including
      atomically thin layers. 

PMID- 25380351
TI  - IMP-3 promotes migration and invasion of melanoma cells by modulating the
      expression of HMGA2 and predicts poor prognosis in melanoma.
AB  - IGF II mRNA-binding protein 3 (IMP-3) has been reported to be a marker of
      melanoma progression. However, the mechanisms by which it impacts melanoma are
      incompletely understood. In this study, we investigate the clinical significance
      of IMP-3 in melanoma progression and also its underlying mechanisms. We found
      that IMP-3 expression was much higher in advanced-stage/metastatic melanomas and
      that it was associated with a poor prognosis (P=0.001). Univariate analysis
      showed that IMP-3 expression was associated with stage III/IV melanomas (odds
      ratio=5.40, P=0.031) and the acral lentiginous subtype (odds ratio=3.93,
      P=0.0034). MeWo cells with overexpression of IMP-3 showed enhanced proliferation
      and migration and significantly increased tumorigenesis and metastatic ability in
      nude mice. We further demonstrated that IMP-3 could bind and enhance the
      stability of the mRNA of high mobility group AT-hook 2 (HMGA2). It was also
      confirmed that IMP-3 had an important role in melanoma invasion and metastasis
      through regulating HMGA2 mRNA expression. IMP-3 expression was positively
      correlated with HMGA2 expression in melanoma cells and also in melanoma tissues.
      Our results show that IMP-3 expression is a strong prognostic factor for
      melanoma, especially acral lentiginous melanoma. 

PMID- 25380350
TI  - Anti-apoptotic NF-kappaB and "gain of function" mutp53 in concert act pro
      apoptotic in response to UVB+IL-1 via enhanced TNF production.
AB  - In response to genotoxic stress, including UVB radiation, transcription factors
      NF-kappaB and p53 inevitably influence the cellular fate. Loss of p53 function
      has been attributed to malignant transformation and interferes with therapeutic
      interventions, whereas "gain of function" mutants even enhance tumor promotion.
      Constitutive NF-kappaB activation is linked to tumor maintenance and resistance
      against chemotherapy. The cross talk between p53 and NF-kappaB, however, is still
      under debate. Using the non-transformed keratinocyte cell line HaCaT, we shed
      light on the interplay between p53 and NF-kappaB by providing clear evidence that
      chronically activated NF-kappaB together with designated "gain of function"
      mutp53 promotes apoptosis via cooperative tumor necrosis factor (TNF) production
      in response to UVB+IL-1. Performing chromatin immunoprecipitation analysis we
      demonstrate that both transcription factors bind to the TNF promoter, whereas UVB
      induced inhibition of Ser-Thr-phosphatase protein phosphatase 2A facilitates
      prolonged phosphorylation of NF-kappaB and the transcriptional cofactor cAMP
      response element-binding protein, both being required for extended TNF
      transcription. Thus, two major anti-apoptotic factors, NF-kappaB and mutp53, in
      concert may generate pro-apoptotic responses. As human skin is constantly exposed
      to UVB, causing IL-1 production as well, we hypothesize that the remarkable
      amount of hotspot p53 mutations within the epidermis (4%) may serve a protective
      function to eliminate precancerous cells at an early stage.

PMID- 25380354
TI  - In ovo and in vitro susceptibility of American alligators (Alligator
      mississippiensis) to avian influenza virus infection.
AB  - Avian influenza has emerged as one of the most ubiquitous viruses within our
      biosphere. Wild aquatic birds are believed to be the primary reservoir of all
      influenza viruses; however, the spillover of H5N1 highly pathogenic avian
      influenza (HPAI) and the recent swine-origin pandemic H1N1 viruses have sparked
      increased interest in identifying and understanding which and how many species
      can be infected. Moreover, novel influenza virus sequences were recently isolated
      from New World bats. Crocodilians have a slow rate of molecular evolution and are
      the sister group to birds; thus they are a logical reptilian group to explore
      susceptibility to influenza virus infection and they provide a link between birds
      and mammals. A primary American alligator (Alligator mississippiensis) cell line,
      and embryos, were infected with four, low pathogenic avian influenza (LPAI)
      strains to assess susceptibility to infection. Embryonated alligator eggs
      supported virus replication, as evidenced by the influenza virus M gene and
      infectious virus detected in allantoic fluid and by virus antigen staining in
      embryo tissues. Primary alligator cells were also inoculated with the LPAI
      viruses and showed susceptibility based upon antigen staining; however, the
      requirement for trypsin to support replication in cell culture limited
      replication. To assess influenza virus replication in culture, primary alligator
      cells were inoculated with H1N1 human influenza or H5N1 HPAI viruses that
      replicate independent of trypsin. Both viruses replicated efficiently in culture,
      even at the 30 C temperature preferred by the alligator cells. This research
      demonstrates the ability of wild-type influenza viruses to infect and replicate
      within two crocodilian substrates and suggests the need for further research to
      assess crocodilians as a species potentially susceptible to influenza virus
      infection.

PMID- 25380353
TI  - Affective, sensory and empathic sharing of another's pain: The Empathy for Pain
      Scale.
AB  - BACKGROUND: Through two studies, we introduce and validate the Empathy for Pain
      Scale (EPS), which characterizes the phenomenology of empathy for pain, including
      the vicarious experience of pain when seeing others in pain. METHODS: In study 1,
      406 individuals completed the EPS and Interpersonal Reactivity Index (IRI). In
      the EPS, four painful scenarios (witnessing surgery, patient recovering from
      surgery, assault and accidental injury) were rated for 12 emotional, empathic and
      sensory responses. In study 2, 59 participants completed the same questionnaires
      and then watched and rated videos of sporting injuries. RESULTS: In study 1, we
      identified three factors of the EPS with principal component analysis, which were
      validated with confirmatory factor analysis: affective distress; vicarious pain;
      and empathic concern. The EPS demonstrated good psychometric properties, re-test
      reliability (n = 105) and concurrent validity. In study 2, we validated the EPS
      against empathic reactions to the pain of others as displayed in video clips
      depicting sporting injuries and showed that the scale has unique utility to
      characterize empathic reactions to pain above general trait empathy measures.
      Both studies showed that the affective distress and empathic concern subscales of
      the EPS correlated with measures of cognitive and affective empathy from the IRI,
      whereas the vicarious pain subscale was only correlated with the personal
      distress IRI subscale. CONCLUSIONS: The EPS is a psychometrically sound new scale
      that characterizes empathy for pain and vicarious pain. The EPS offers valuable
      insight to the phenomenological profile of the affective, empathic and sensory
      dimensions of empathy for pain.

PMID- 25380355
TI  - Anticoagulant rodenticide exposure and toxicosis in coyotes (Canis latrans) in
      the Denver Metropolitan Area.
AB  - Anticoagulant rodenticides are widely used in urban areas to control rodent pests
      and are responsible for secondary poisoning in many nontarget wildlife species.
      We tested the livers of five coyotes (Canis latrans) in the Denver Metropolitan
      Area, Colorado, US, for anticoagulant rodenticides. All five livers were positive
      for brodifacoum, with values ranging from 95 ppb to 320 ppb, and one liver was
      positive for bromadiolone, with a value of 885 ppb. Both of these rodenticides
      are second-generation anticoagulants, which are more potent and more likely to
      cause secondary poisoning than first-generation anticoagulants due to their
      accumulation and persistence in the liver. We concluded that exposure to these
      rodenticides may have caused the death of at least two of the five coyotes, and
      urban coyotes in our study area are commonly exposed to rodenticides.

PMID- 25380356
TI  - Antigen detection, rabies virus isolation, and Q-PCR in the quantification of
      viral load in a natural infection of the North American beaver (Castor
      canadensis).
AB  - All mammals are believed susceptible to rabies virus infection, yet transmission
      from nonreservoir hosts to humans is uncommon. However, interactions between
      nonreservoir hosts and humans occur frequently and risk of exposure increases
      where rabies is enzootic. We describe rabies and apparent pantropism of rabies
      virus in a beaver (Castor canadensis).

PMID- 25380358
TI  - Isolation of type A influenza viruses from Red-necked Grebes (Podiceps
      grisegena).
AB  - Six type-A low pathogenic influenza viruses from 14 Red-necked Grebes (Podiceps
      grisegena) from Agassiz National Wildlife Refuge were sequenced. The grebe
      viruses were closely related to North American duck viruses. The genetic and
      temporal subtype consistency between the duck and grebe isolates suggest
      spillover events, potentially enhanced by feather eating.

PMID- 25380357
TI  - Multiplex serology for common viral infections in feral pigs (Sus scrofa) in
      Hawaii between 2007 and 2010.
AB  - Multiplex serology was performed for the detection of total immunoglobulin (Ig)
      and IgM antibodies against porcine circovirus type 2 (PCV2), porcine reproductive
      and respiratory syndrome virus (PRRSV), and swine influenza virus (SIV) antigens
      in feral swine (Sus scrofa). Serum samples were collected from the islands of
      Oahu (292 pigs) and Hawaii (52 pigs) between 2007 and 2010. The highest antibody
      prevalence was to PCV2 (63%), followed by SIV (7.8%) and PRRSV (5.8%). Antigen
      specific IgM was detected at a much lower prevalence. PCR amplification and
      sequence analysis of PCV2 in three IgM-positive samples identified PCV2b as the
      only genotype. While the prevalence of PCV2 and PRRSV remained similar between
      2007 and 2010, the percentage of SIV-positive samples on Oahu increased from 2%
      to 19%. Our results demonstrate the utility of multiplex serology for pathogen
      surveillance in feral pig populations.

PMID- 25380359
TI  - Ketamine and midazolam anesthesia in Pacific martens (Martes caurina).
AB  - Abstract The use of midazolam as a tranquilizer for anesthesia in mustelids in
      conjunction with the cyclohexamine ketamine is not well documented. Because
      midazolam is fast acting, inexpensive, and quickly metabolized, it may serve as a
      good alternative to other more commonly used tranquilizers. We trapped and
      anesthetized 27 Pacific martens (Martes caurina) in Lassen National Forest
      (northern California, US) August 2010-April 2013. We assessed anesthesia with
      ketamine at 18 and 25 mg/kg combined with 0.2 mg/kg of midazolam by comparing
      mean times of induction, return to consciousness, and recovery, plus physiologic
      parameters. No reversal was used for the midazolam portion of the anesthetic.
      Mean (+/-SD) induction for both ketamine dosages was 1.7+/-0.5 and 1.8+/-1.0 min,
      respectively. Return to consciousness mean times were 8.0 min longer (P<0.001)
      for martens receiving a 25 mg/kg ketamine dosage. Mean recoveries were 15.1 min
      longer (P<0.003) for the 25 mg/kg ketamine dosage. Physiologic parameter means
      were similar for both ketamine dosages with no statistically significant
      differences. Body temperatures and heart and respiratory rates were generally
      stable, but percentage of oxygen saturation and end tidal carbon dioxide values
      were below those seen in previous mustelid studies. The combination of ketamine,
      at both dosages, and midazolam provided reliable field anesthesia for Pacific
      martens, and supplemental oxygen is recommended as needed. 

PMID- 25380360
TI  - Distinguishing disease effects from environmental effects in a mountain ungulate:
      seasonal variation in body weight, hematology, and serum chemistry among Iberian
      ibex (Capra pyrenaica) affected by sarcoptic mange.
AB  - Our study focuses on the Iberian ibex (Capra pyrenaica) from the Sierra Nevada
      Natural Space (southern Spain), where sarcoptic mange is an endemic disease and
      animals are affected by a highly seasonal environment. Our aim was to distinguish
      between disease and environmental influences on seasonal variation in body
      weight, hematology, and serum biochemistry in Iberian ibex. We sampled 136
      chemically immobilized male ibexes. The single effect of mange influenced
      hemoglobin, hematocrit, mean corpuscular volume, leukocytes, band neutrophils,
      monocytes, cholesterol, urea, creatine, and aspartate aminotransferase. Both
      mange and the period of the year also affected values of mean corpuscular
      hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, glucose, and
      serum proteins. Scabietic animals showed a marked reduction in body weight (21.4
      kg on average), which was more pronounced in winter. These results reveal that 1)
      infested animals are anemic, 2) secondary infections likely occur, and 3)
      sarcoptic mange is catabolic.

PMID- 25380361
TI  - Bartonella spp. in a Puerto Rican bat community.
AB  - We captured and sampled 68 bats of six species from a shared roosting site in
      Puerto Rico in April 2012. Bats were screened for Bartonella spp. by culture and
      confirmed by PCR and sequencing for the gltA gene. Bartonella cultures were
      obtained from blood specimens of 9/51 (18%) individuals from three species
      (Artibeus jamaicensis, Brachyphylla cavernarum, and Monophyllus redmani).
      Phylogenetic analysis of the gltA sequences showed that M. redmani was infected
      with multiple, diverse Bartonella strains, and A. jamaicensis was infected with a
      strain related to a strain from a congeneric host. Ectoparasite load could
      possibly explain observed differences in Bartonella diversity and prevalence
      between bat species in this community, and we suggest future research to
      substantiate these preliminary findings.

PMID- 25380362
TI  - Prevalence of Theileria equi and Babesia caballi as well as the identification of
      associated ticks in sympatric Grevy's zebras (Equus grevyi) and donkeys (Equus
      africanus asinus) in northern Kenya.
AB  - The role of equine piroplasmosis as a factor in the population decline of the
      Grevy's zebra is not known. We determined the prevalence of Babesia caballi and
      Theileria equi in cograzing Grevy's zebras (Equus grevyi) and donkeys (Equus
      africanus asinus) in northern Kenya and identified the associated tick vectors.
      Blood samples were taken from 71 donkeys and 16 Grevy's zebras from March to May
      2011. A nested PCR reaction using 18s ribosomal (r)RNA primers on 87 blood spots
      showed 72% (51/71; 95% confidence interval [CI] 60.4-81.0%) of donkeys and 100%
      (16/16; 95% CI, 77.3-100%) of Grevy's zebras were T. equi positive. No samples
      were positive for B. caballi. Sequence comparison using the National Center for
      Biotechnology Information's basic local alignment search tool identified
      homologous 18s rRNA sequences with a global geographic spread. The T. equi
      derived sequences were evaluated using Bayesian approaches with independent
      Metropolis-coupled Markov chain Monte Carlo runs. The sequences clustered with
      those found in Sudan, Croatia, Mongolia, and the US, with statistical support
      greater than 80% for the two main clades. Hyalomma tick species were found on
      both donkeys and Grevy's zebras, whereas Rhipicephalus pulchellus was found
      exclusively on Grevy's zebras and Hyalomma marginatum rupfipes on donkeys. The
      prevalence of T. equi was 100% in Grevy's zebras and 72% in donkeys with common
      tick vectors identified. Our results suggest that donkeys and Grevy's zebras can
      be asymptomatic carriers and that piroplasmosis is endemic in the study area.

PMID- 25380363
TI  - Feline immunodeficiency virus and feline leukemia virus infection in free-ranging
      guignas (Leopardus guigna) and sympatric domestic cats in human perturbed
      landscapes on Chiloe Island, Chile.
AB  - Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are two of
      the most common viruses affecting domestic cats (Felis catus). During the last
      two decades, reports show that both viruses also infect or affect other species
      of the family Felidae. Human landscape perturbation is one of the main causes of
      emerging diseases in wild animals, facilitating contact and transmission of
      pathogens between domestic and wild animals. We investigated FIV and FeLV
      infection in free-ranging guignas (Leopardus guigna) and sympatric domestic cats
      in human perturbed landscapes on Chiloe Island, Chile. Samples from 78 domestic
      cats and 15 guignas were collected from 2008 to 2010 and analyzed by PCR
      amplification and sequencing. Two guignas and two domestic cats were positive for
      FIV; three guignas and 26 domestic cats were positive for FeLV. The high
      percentage of nucleotide identity of FIV and FeLV sequences from both species
      suggests possible interspecies transmission of viruses, facilitated by increased
      contact probability through human invasion into natural habitats, fragmentation
      of guigna habitat, and poultry attacks by guignas. This study enhances our
      knowledge on the transmission of pathogens from domestic to wild animals in the
      global scenario of human landscape perturbation and emerging diseases.

PMID- 25380364
TI  - Identification of avian coronavirus in wild aquatic birds of the central and
      eastern USA.
AB  - Coronaviruses (CoVs) are worldwide in distribution, highly infectious, and
      difficult to control because of their extensive genetic diversity, short
      generation time, and high mutation rates. Genetically diverse CoVs have been
      reported from wild aquatic birds that may represent a potential reservoir for
      avian CoVs as well as hosts for mutations and recombination events leading to new
      serotypes or genera. We tested 133 pooled samples representing 700 first-passage
      (in eggs) and 303 direct cloacal swab transport media samples from wild aquatic
      birds in the US that were avian influenza-negative. We isolated RNA from frozen
      samples and performed reverse transcriptase-PCR using a published universal CoV
      primer set. Of the samples tested, one from a Ruddy Turnstone (Arenaria
      interpres) was positive for CoV, showing nucleotide sequence similarity to a duck
      coronavirus (DK/CH/HN/ZZ2004). These data indicate a possible low prevalence of
      CoVs circulating in wild aquatic birds in the eastern half of the US.

PMID- 25380365
TI  - Risk factors associated with prevalence of antibodies to Leptospira interrogans
      in a metapopulation of black-tailed prairie dogs in Mexico.
AB  - Interest in the study of infectious diseases of wildlife has grown in recent
      decades and now focuses on understanding host-parasite dynamics and factors
      involved in disease occurrence. The black-tailed prairie dog (Cynomys
      ludovicianus) is a useful species for this type of investigation because it lives
      in heterogeneous landscapes where human activities take place, and its
      populations are structured as a metapopulation. Our goal was to determine if
      colony area, density, and proximity to human settlements are associated with
      prevalence of antibodies to Leptospira interrogans in black-tailed prairie dogs
      of northwestern Chihuahua State, Mexico. We captured 266 prairie dogs in 11
      colonies in 2009 and analyzed 248 serum samples with the microscopic
      agglutination test (MAT) for antibody to any of the 12 pathogenic serovars of L.
      interrogans. Serologically positive test results for only serovars Bratislava,
      Canicola, Celledoni, and Tarassovi were considered for statistical analysis.
      Almost 80% of sera were positive for at least one pathogenic serovar (MAT titer
      >=1?80). The highest recorded antibody prevalences were to serovars Bratislava
      and Canicola. Correlation analysis showed a negative relationship between L.
      interrogans antibody prevalence and colony area (r = -0.125, P<0.005), suggesting
      that animals living in larger colonies were at a lower risk than those in smaller
      colonies. The correlation between the serovar Canicola and distance was negative
      (r = -0.171, P<0.007), and this relationship may be explained by the presence of
      domestic dogs associated with human dwellings. This is the first study of
      Leptospira spp. antibody prevalence in prairie dogs, and it provides valuable
      insights into the dynamics of leptospirosis in threatened wildlife species.
      Further studies are needed to evaluate the impact of Leptospira serovars in
      metapopulations of prairie dogs and other domestic and wild mammals in grassland
      communities.

PMID- 25380366
TI  - Serologic, trace element, and fecal parasite survey of free-ranging, female mule
      deer (Odocoileus hemionus) in eastern Washington, USA.
AB  - Blood and fecal samples collected from 97 free-ranging mule deer (Odocoileus
      hemionus), from four distinct herds during the spring of 2000 or 2001 in eastern
      Washington, US, were tested for exposure to selected pathogens, concentrations of
      trace elements, and presence of parasites in feces. Antibodies were detected to
      the following: Leptospira interrogans serovar Bratislava (4%), Leptospira
      interrogans serovar Canicola (1%), Leptospira interrogans serovar Grippotyphosa
      (13%), Bovine viral diarrhea virus 1 (57%), Bovine respiratory syncytial virus
      (71%), Infectious bovine rhinotracheitis virus (51%), Bovine parainfluenza virus
      3 (61%), Bluetongue virus (25%), and Epizootic hemorrhagic disease virus (25%); 3
      of 63 (5%) samples had antibody to Neospora spp. All samples tested for antibody
      to Brucella abortus and L. interrogans serovar Icterohaemorrhagiae, L.
      interrogans serovar Pomona, and L. interrogans serovar Hardjo samples were
      negative. Trace element concentrations from 97 sera were deficient for selenium
      (17%), copper (19%), iron (34%), calcium (3%), and phosphorus (2%) compared with
      thresholds established for domestic livestock. Parasites detected in 97 fecal
      samples included dorsal-spined larvae (probably Parelaphostrongylus sp.) (40%),
      abomasal nematode eggs (1%), Capillaria sp. eggs (1%), Nematodirus sp. eggs
      (26%), Moniezia sp. eggs (1%), and Eimeria sp. (2%).

PMID- 25380367
TI  - Postmortem findings in four south American sea lions (Otaria byronia) from an
      urban colony in Valdivia, Chile.
AB  - We performed postmortem examination on four South American sea lions (Otaria
      byronia) from an urban colony in Valdivia, Chile. Chronic leptospirosis and
      suspected morbillivirus-like infection were diagnosed in one individual.
      Antibodies against Toxoplasma gondii and the zoonotic helminthes Contracaecum
      sp., Pseudoterranova sp., and Diphyllobothrium sp. were also detected.

PMID- 25380368
TI  - Isolation of pathogenic Yersinia enterocolitica 1B/O:8 from Apodemus mice in
      Japan.
AB  - Yersinia enterocolitica was isolated from 15.7% (88/560) of wild rodents captured
      in 15 prefectures in Japan. Prevalences by rodent species were 18.0% (70/388) in
      Japanese field mice (Apodemus speciosus), 20% (14/71) in small Japanese field
      mice (Apodemus argenteus), and 11% (4/38) in gray red-backed vole (Myodes
      rufocanus bedfordiae), suggesting that these rodent species are important
      reservoirs of Y. enterocolitica. Although most of the isolates were identified as
      biotype 1A, the pathogenic bioserotype 1B/O:8 was detected in one of the A.
      speciosus and in three of the A. argenteus captured in Aomori Prefecture. It is
      suggested that Apodemus mice may be an important reservoir of Y. enterocolitica,
      and that there are foci of the pathogenic bioserotype 1B/O:8 in Aomori
      Prefecture, because human sporadic cases by the serotype have been reported in
      this prefecture.

PMID- 25380369
TI  - Aerobic bacterial microbiota isolated from the cloaca of the European pond turtle
      (Emys orbicularis) in Poland.
AB  - We conducted a comparative analysis of the aerobic cloacal bacteria of European
      pond turtles (Emys orbicularis) living in their natural environment and juvenile
      turtles reared under controlled conditions in a breeding center. We included 130
      turtles in the study. The aerobic bacteria isolated from the cloaca of the
      juvenile turtles were less diverse and more prevalent than the bacteria isolated
      from free-living adults. We isolated 17 bacterial species from juvenile captive
      turtles, among which the dominant species were Cellulomonas flavigena (77/96),
      Enterococcus faecalis (96/96), Escherichia coli (58/96), and Proteus mirabilis
      (41/96). From the adult, free-living turtles, we isolated 36 bacterial species,
      some of which are a potential threat to public health (e.g., Salmonella enterica
      serovars Newport, Daytona, and Braenderup; Listeria monocytogenes; Yersinia
      enterocolitica; Yersinia ruckeri; Klebsiella pneumoniae; Vibrio fluvialis; and
      Serratia marcescens), and pathogens that are etiologic agents of diseases of
      ectothermic animals (e.g., Aeromonas sobria, Aeromonas caviae, Hafnia alvei,
      Edwardsiella tarda, and Citrobacter braakii; the last two species were isolated
      from both groups of animals). The cloacal bacterial biota of the European pond
      turtle was characterized by numerous species of bacteria, and its composition
      varied with turtle age and environmental conditions. The small number of isolated
      bacteria that are potential human pathogens may indicate that the European pond
      turtle is of relatively minor importance as a threat to public health.

PMID- 25380371
TI  - [Health promotion: a new approach in Africa].

PMID- 25380370
TI  - Induction of Nrf2-mediated genes by Antrodia salmonea inhibits ROS generation and
      inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages.
AB  - Antrodia salmonea (AS), a well-known medicinal mushroom in Taiwan, has been
      reported to exhibit anti-oxidant, anti-angiogenic, anti-atherogenic, and anti
      inflammatory effects. In the present study, we investigated the activation of
      Nrf2-mediated antioxidant genes in RAW264.7 macrophages by the fermented culture
      broth of AS, studied the resulting protection against lipopolysaccharide (LPS)
      stimulated inflammation, and revealed the molecular mechanisms underlying these
      protective effects. We found that non-cytotoxic concentrations of AS (25-100 MUg
      mL-1) protected macrophages from LPS-induced cell death and ROS generation in a
      dose-dependent manner. The antioxidant potential of AS was directly correlated
      with the increased expression of the antioxidant genes HO-1, NQO-1, and gamma
      GCLC, as well as the level of intracellular GSH followed by an increase in the
      nuclear translocation and transcriptional activation of the Nrf2-ARE pathway.
      Furthermore, Nrf2 knockdown diminished the protective effects of AS, as evidenced
      by the increased production of pro-inflammatory cytokines and chemokines,
      including PGE2, NO, TNF-alpha, and IL-1beta, in LPS-stimulated macrophages.
      Notably, AS treatment significantly inhibited LPS-induced ICAM-1 expression in
      macrophages. Our data suggest that the anti-inflammatory potential of Antrodia
      salmonea is mediated by the activation of Nrf2-dependent antioxidant defense
      mechanisms. Results support the traditional usage of this beneficial mushroom for
      the treatment of free radical-related diseases and inflammation.

PMID- 25380372
TI  - [Health promotion: an issue at the heart of our editorial concerns].

PMID- 25380373
TI  - [Health promotion in Africa: history and prospects].
AB  - Since the Ottawa Charter (1986), the majority of regions of the world has done
      considerable progress in health promotion (HP) and has got frameworks of
      reflection, methodologies and tools related to it. In Africa, HP was adopted by
      the Member States of the WHO regional office of Africa since 2001. However many
      efforts remain to be deployed at countries' level for its appropriation in the
      context of the triple burden of communicable diseases, non-communicable diseases
      and socio-behavioral over the region. Francophone Africa barely begins to take
      its first steps in the recognition and adoption of this approach. It favors
      however strategies such as information, education and communication (IEC), health
      education (HE), behavior change communication (BCC), social mobilization, social
      marketing, etc. Things are stressed and done under HP theme without for as much
      fit in its characteristics. What is the current situation in francophone Africa ?
      The particularities of HP evolution in this region and its practice by
      professionals with regard to the priority health issues of the region deserve
      reflection. This is the question to which it is proposed to answer in this
      article. We will review, among other things, HP history and why it matters, then
      briefly the various concepts and strategies used. We will finish by the potential
      development of HP in the region. 

PMID- 25380374
TI  - [Evaluation: an avenue to improvement of health promotion in Africa?].
AB  - Are the methods used to evaluate health promotion interventions in Africa adapted
      to the specificities of this field ? The authors try to answer this question
      based on reflective analysis of four evaluations that they conducted in Benin,
      Burkina Faso and Mali. The experiences reported illustrate the desire to conduct
      the evaluation approach in line with the principles of health promotion but also
      the difficulties involved to overcome the obstacles to practical application of
      evaluation. Considerable progress has yet to be made to ensure that evaluation
      fully meets the expectations of stakeholders and the values of health promotion :
      all of the dynamics generated by health promotion interventions must be taken
      into account, equity must be integrated at the heart of the reflection,
      innovative practices must be supported in view of their durability. Because it
      facilitates the emergence and sharing of multiple visions of this still poorly
      defined concept, evaluation constitutes an avenue to improvement of health
      promotion in Africa.

PMID- 25380375
TI  - [Health promotion in Cameroon: current situation and prospects].
AB  - Health promotion (HP) is insufficiently implemented in Cameroon, despite a
      ministerial body in charge of HP. Health promotion activities are essentially
      limited to disease prevention and health education, while social determinants of
      health are virtually ignored. Although the Ottawa Charter constitutes the basic
      guidelines for HP, it presents a number of weaknesses when applied to the field,
      as the actions conducted do not comprise all lines of intervention of the
      charter. No action plane and no precise HP objectives have been defined and its
      conceptual framework is still poorly understood by the various stakeholders of
      the health system. Health is still considered to result from organization of
      health care and can only be ensured by medical personnel. In view of this fairly
      critical analysis of HP in Cameroon, concrete actions must be conducted to
      acquire a better knowledge of the conceptual framework of health promotion and
      its real application. Based on a critical review of the available literature on
      the social and health situation of Cameroon and the current status of HP, this
      article proposes actions to be conducted on organizational and political levels
      to ensure that HP has a real place in Cameroon and in order to improve
      significantly health indicators in this country. This approach inevitably
      requires the development of policies in favour of HP, reinforcement of HP
      capacities and finally the development of university structures specialized in HP
      practices and research. 

PMID- 25380376
TI  - [Community-based approaches in the fight against Buruli ulcer : review of the
      literature].
AB  - Buruli ulcer (BU) is an infectious skin disease caused by Mycobacterium ulcerans.
      It mainly affects poor communities living close to bodies of water. In the
      absence of early treatment, this "neglected" disease can cause lasting
      deformities and may require limb amputation. It is reported in 34 countries and
      is the third most common mycobacterial disease in immunocompetent patients.
      Considerable progress has been made in treatment and prevention. The Cotonou
      Declaration (2009) describes the recommended control strategies. Although
      effective, current control strategies are limited because they do not take into
      account all the factors that influence emergence, prevention and cure of the
      disease. The control of Buruli ulcer mainly depends on intervention on social,
      cultural and psychosocial factors that influence preventive and self-care
      behaviour. The health promotion approach requires collaboration with populations
      in order to perform simultaneous actions on BU factors in the community setting.
      Although effective on many health problems, health promotion is not applied in
      the fight against BU due to the absence of action on all factors such as poverty.
      This article presents a review of the literature on BU strategies and community
      approaches. 407 relevant articles published in 1998-2013 period were examined.
      Eleven programmes are based on a top-down approach, which does not include
      populations in decision-making processes, unlike the bottom-up participatory
      approaches recommended in health promotion. Three health promotion programmes and
      6 community-based participatory approaches were identified and examined.
      Community participation and empowerment constitute the basis for a community
      approach in the fight against Buruli ulcer.

PMID- 25380377
TI  - ["Protect the next generation": promote the end of female genital mutilation in
      the Kayes health district in Mali].
AB  - Female genital mutilation (FGM) comprises all procedures that involve partial or
      total removal of the external female genitalia, or other injury to the female
      genital organs for non-medical reasons. FGM is not just a public health problem,
      but a violation of the human rights of girls and women. Equilibres & Populations
      and AMSOPT are developing a pilot project designed to promote abandonment of FGM
      in the Kayes health district by demonstrating that social change is possible and
      reproducible. The strategy is based on the organized diffusion of change among
      communities linked by marital ties. The communication process is based on
      promotion of health and human rights. The project collaborates with political and
      social actors so that they can take charge of the ongoing changes. The project
      also works in France with migrants from villages involved in these interventions
      because they also have an important role to play. Evaluation of the results
      showed that 80 of the 250 villages of the district declared abandonment of FGM. A
      positive debate is emerging in the communities, but messages must be repeated.
      The response of the health system has been reinforced, as 1328 women received
      medical care for complications of excision. The project now needs to be further
      developed in order to achieve its goals. Although the search for funding has been
      an obstacle, the acquisition of pluriannual funds will provide greater
      flexibility in management of the project. Beyond abandonment of FSM, the project
      also wants to reinforce the status and health of women and give them the
      possibilities to defend their rights. 

PMID- 25380379
TI  - [Facilitating access to care for most-at-risk populations : the Bamako night
      sexual health clinic experience (Mali)].
AB  - The estimated prevalence of HIV in Mali is 1.3 % of the general population. The
      epidemic is concentrated in certain groups, particularly men who have sex with
      men (MSM) and sex workers (SW). Access to care is limited for these populations,
      notably because of structural obstacles (e.g. marked social rejection ; health
      care services poorly adapted to the real needs of these people). Innovative
      strategies must be envisaged to ensure access to care services and retention in
      care for these populations. As part of a health promotion process, ARCAD-SIDA, a
      Malian NGO involved in the fight against AIDS since 1995, set up a night sexual
      health clinic in 2010 as part of a strategy to more adequately respond to the
      health needs of these populations. This clinic adapts health service timetables
      to match the lifestyles of the targeted populations, brings services in closer
      physical proximity to the places in which these populations live, proposes
      patient-tailored consultations, works to improve the patients' psychosocial
      skills, and promotes community-based peer mobilization. In an environment which
      is generally hostile to MSM and SW, ARCAD-SIDA also works in advocacy, targeting
      political decision-makers, defense forces and journalists. The NGO has also
      played a key role in ensuring that these populations are taken into account in
      the national strategy for the fight against HIV. Since opening in 2010, the
      clinic has helped reach a large number of MSM and SW and has improved retention
      in care. This innovative strategy has also enabled the NGO to improve its
      professional practices in terms of an individual-based approach to prevention.
      Interventions that are better adapted to the needs and environment of the
      populations for whom they are intented to have a positive effect on access to and
      use of healthcare services.

PMID- 25380378
TI  - [Promotion of community-based care in Africa: example of community general
      practice in Benin].
AB  - Considerable effort has been made to provide rural African populations with basic
      health care, but the quality of this care remains unsatisfactory due to the
      absence of first-line GPs. This is a paradoxical situation in view of the large
      number of physicians trained in medical schools in French-speaking Africa and
      Madagascar. of the lack of GPs working in rural areas is a real concern, as many
      young doctors remain unemployed in cities. For more than 20 years, the NGO Sante
      Sud has proposed a Community General Medicine concept, which, combined with a
      support system, has allowed the installation of more than 200 community GPs in
      Mali and Madagascar. The advantage of this concept is that it provides family
      medicine and primary health care in the same practice. Since 2009, Sante Sud
      supports an installation project in rural areas of northern Benin, where
      community GPs work independently, as a complementary partner of the public
      sector. Since 2013, the installation process comprises a university degree
      created with the University of Parakou Faculty of Medicine. Based on this
      experience in Benin, the authors show that the presence of a first-line general
      practitioner is an original strategy that provides a major contribution to health
      promotion : reducing health inequalities between rural and urban populations,
      allowing women to receive medically assisted childbirth close to home, developing
      family planning activities, education and health care for chronic diseases,
      strengthening health coverage by participating in vaccination campaigns, etc. Due
      to their functions and proximity, community GPs represent an added value for
      health promotion.

PMID- 25380380
TI  - [Exploratory study of road safety in Brazzaville and Pointe-Noire in Republic of
      the Congo].
AB  - Although road accidents in the Congo are reaching alarming levels (2,720
      accidents in 2010 and 3,126 accidents in 2011), especially with the massive
      arrival of "Jakarta" mopeds, no evaluation has been conducted to identify and
      understand the factors responsible for this problem. This article reports the
      results of an exploratory study conducted in Brazzaville and Pointe-Noire based
      on information collected from existing documents and by semidirective
      questionnaire of people from various sectors able to elucidate the problem of
      road safety. Using William Haddon's matrix, the parameters investigated were :
      road user behaviour ; environmental and technological factors ; characteristics
      of road accident victims ; quality of care ; intervention times and organization
      of prevention. This study demonstrated the absence of a road safety policy in
      Congo. It also showed that the main factors responsible for road accidents are
      behavioural (failure to wear safety belts, failure to comply with road signs,
      fatigue, use of a telephone while driving, etc.), followed by environmental and
      technological factors (insufficient traffic lights, absence of sidewalks,
      disorganized occupation of roads, general state of vehicles). This study shows
      that, in order to improve road safety in the Congo, it is essential to promote
      the development of national road safety policies and an action plan, intervention
      on the determinants of road accidents, and a change of road user behaviours
      (compulsory use of safety belts, ban on the use of a telephone and smoking while
      driving, etc.). Effective organization of the management of road accident victims
      and allocation of a budget to implement a road safety policy are also necessary.

PMID- 25380381
TI  - [Health programme evaluation training in Africa : personal experience and
      discussion].
AB  - There is still a major need for health programme evaluation training in French
      speaking West Africa. Based on a ten-year experience of this type of training in
      a number of countries, this review article describes and discusses the content of
      proposed training programmes. These short vocational and participative training
      programmes concern the essential themes of evaluation practice : general
      introduction to the concepts and the evaluation approach, the pre-evaluation
      phase and intervention theory/logic, the various approaches to (participative,
      directive, etc.) and types of evaluation (needs, implantation, process, efficacy,
      etc.), data collection methods and tools, communication and use of the results,
      professional practice standards. Reflective analysis shows that a non-directive,
      participative educational approach, based on case studies is highly appreciated
      by participants. Several essential elements of professional evaluation practice
      are perceived as very novel by participants : the pre-evaluation phase, the
      rigorous approach, the primary concern for the usefulness of the results,
      practice standards. Quantitative analyses are well known, but not well utilized
      and qualitative analyses are poorly known and poorly understood. The deployment
      of health promotion evaluation programme training has become essential. It is
      consubstantial with rigorous professional practice, which must be useful to
      decision-makers in Africa.

PMID- 25380382
TI  - [The "health promotion" approach, a strategic alternative to teenagers' health in
      the Democratic Republic of Congo?].
AB  - This paper describes a review of the possibilities of improving HIV/AIDS
      prevention and reproductive health of teenagers and adolescents in the Democratic
      Republic of Congo (DRC). This approach was based on compilation of institutional,
      political, legislative and national strategy data. The document review was
      completed by information collected from 15 key informants and by direct
      observation of the work of peer educators and community workers, allowing
      evaluation of the possibilities of development of the priority domains of the
      Ottawa Charter for Health Promotion in young adolescents. Health promotion
      interventions for adolescents are globally ensured institutionally by three
      specialized programmes of the Ministry of Health, in collaboration with numerous
      national and international partners. Organized operationally outside of the
      primary health care circuit, strategic actions are more specifically directed
      towards acquisition of knowledge than individual skills by means of IEC
      (information, education and communication) and (BCC) (behaviour change
      communication) approaches, but with disappointing results. Although traces of
      these five priority domains of the Ottawa Charter are perceptible in the national
      response to the health problems of adolescents, the work of the various actors is
      not coordinated and organized in compliance with health promotion guidelines. The
      training of health workers appears to be a major determinant to structure this
      response around a dynamic federating the actions of all stakeholders to orient
      them towards the options of the health promotion approach. 

PMID- 25380383
TI  - Simultaneous determination of a novel oral Janus kinase inhibitor ASP015K and its
      sulfated metabolite in rat plasma using LC-MS/MS.
AB  - A sensitive and selective liquid chromatography with tandem mass spectrometry (LC
      MS/MS) was developed for determining the concentrations of novel Janus kinase
      inhibitor ASP015K and its sulfated metabolite M2 in rat plasma. This method
      involves solid-phase extraction (SPE) from 25 MUL of rat plasma. LC separation
      was performed on an Inertsil PH-3 column (100 mm L *4.6 mm I.D., 5 um) with a
      mobile phase consisting of 10 mM ammonium acetate and methanol under linear
      gradient conditions. Analytes were introduced to the LC-MS/MS through an
      electrospray ionization source and detected in positive-ion mode using selected
      reaction monitoring. Standard curves were linear from 0.25 to 500 ng/mL (r
      >=0.9964). This assay enabled quantification of ASP015K and M2 at a concentration
      as low as 0.25 ng/mL in rat plasma. Validation data demonstrated that the method
      is selective, sensitive and accurate. Further, we also successfully applied this
      method to a preclinical pharmacokinetic study in rats.

PMID- 25380384
TI  - Outcomes of a hospital-based employee lactation program.
AB  - BACKGROUND: Little has been published about employee lactation support in
      hospitals and other healthcare facilities. The Children's Hospital of
      Philadelphia (CHOP), Philadelphia, PA, has a comprehensive employee lactation
      program. The objective of this study was to describe the breastfeeding practices
      of our employees and compare these results with national Centers for Disease
      Control and Prevention (CDC) data. MATERIALS AND METHODS: The human resources
      department generated a list of all employees who filed for maternity leave
      between 2007 and 2011. These employees were contacted confidentially via e-mail
      to complete an electronic-based (SurveyMonkey.com) questionnaire. An initial
      message and three reminder messages were sent over a 3-month period during the
      last quarter of 2012, with 545 women completing the survey (response rate, 40%).
      RESULTS: Women who responded to the survey had significantly higher breastfeeding
      initiation rates compared with national CDC data (94.5% vs. 76.9%; p<0.0001). At
      6 months, significantly more CHOP employees were breastfeeding (78.6% vs. 47.2%;
      p<0.0001). At 12 months 32.4% of CHOP employees were still breastfeeding compared
      with CDC data of 25.5% (p=0.0003). Additionally, over 20% of CHOP employees
      breastfed their infants for over 12 months (no national data for comparison).
      CONCLUSIONS: Within CHOP's comprehensive employee lactation program, women
      achieved breastfeeding milestones that well exceeded national data and the
      Healthy People 2020 targets for breastfeeding initiation and duration. CHOP's
      employee lactation program can serve as a model for other institutions.

PMID- 25380385
TI  - Particle size distributions of particulate emissions from the ferroalloy industry
      evaluated by electrical low pressure impactor (ELPI).
AB  - The present article presents a comprehensive evaluation of the potential use of
      an Electrical Low Pressure Impactor (ELPI) in the ferroalloy industry with
      respect to indoor air quality and fugitive emission control. The ELPI was used to
      assess particulate emission properties, particularly of the fine particles (Dp <=
      1 MUm), which in turn may enable more satisfactory risk assessments for the
      indoor working conditions in the ferroalloy industry. An ELPI has been applied to
      characterize the fume in two different ferroalloy plants, one producing
      silicomanganese (SiMn) alloys and one producing ferrosilicon (FeSi) alloys. The
      impactor classifies the particles according to their aerodynamic diameter and
      gives real-time particle size distributions (PSD). The PSD based on both number
      and mass concentrations are shown and compared. Collected particles have also
      been analyzed by transmission and scanning electron microscopy with energy
      dispersive spectroscopy. From the ELPI classification, particle size
      distributions in the range 7 nm - 10 MUm have been established for industrial
      SiMn and FeSi fumes. Due to the extremely low masses of the ultrafine particles,
      the number and mass concentration PSD are significantly different. The average
      aerodynamic diameters for the FeSi and the SiMn fume particles were 0.17 and 0.10
      MUm, respectively. Based on this work, the ELPI is identified as a valuable tool
      for the evaluation of airborne particulate matter in the indoor air of
      metallurgical production sites. The method is well suited for real-time
      assessment of morphology (particle shape), particle size, and particle size
      distribution of aerosols. 

PMID- 25380386
TI  - Palladium-catalyzed aromatic C-H bond nitration using removable directing groups:
      regiospecific synthesis of substituted o-nitrophenols from related phenols.
AB  - A general and regiospecific transformation of substituted phenols into the
      related o-nitrophenols has been achieved via a three-step process involving the
      palladium-catalyzed chelation-assisted ortho-C-H bond nitration as the key step.
      In the process, 2-pyridinyloxy groups act as removable directing groups for the
      palladium-catalyzed ortho-nitration of substituted 2-phenoxypridines, and they
      can be readily removed in the subsequent conversion of the resulting 2-(2
      nitrophenoxy)pyridines into 2-nitrophenols. 

PMID- 25380387
TI  - Pseudogap in cuprates driven by D-wave flux-phase order proximity effects: a
      theoretical analysis from Raman and ARPES experiments.
AB  - One of the puzzling characteristics of the pseudogap phase of high-Tc cuprates is
      the nodal-antinodal dichotomy. While the nodal quasiparticles have a Fermi liquid
      behaviour, the antinodal ones show non-Fermi liquid features and an associated
      pseudogap. Angle-resolved photoemission spectroscopy and electronic Raman
      scattering are two valuable tools which have shown universal features which are
      rather material-independent, and presumably intrinsic to the pseudogap phase. The
      doping and temperature dependence of the Fermi arcs and the pseudogap observed by
      photoemission near the antinode correlates with the non-Fermi liquid behaviour
      observed by Raman for the B(1g) mode. In contrast, and similar to the nodal
      quasiparticles detected by photoemission, the Raman B(2g) mode shows Fermi liquid
      features. We show that these two experiments can be analysed, in the context of
      the t-J model, by self-energy effects in the proximity to a D-wave flux-phase
      order instability. This approach supports a crossover origin for the pseudogap,
      and a scenario of two competing phases. The B(2g) mode shows, in an underdoped
      case, a depletion at intermediate energy which has attracted renewed interest. We
      study this depletion and discuss its origin and relation with the pseudogap.

PMID- 25380389
TI  - Novel uranyl(VI) complexes incorporating propylene-bridged salen-type N2O2
      ligands: a structural and computational approach.
AB  - The synthesis of the tetradentate dianionic ligand, H2L (2,2'-(1E,1'E)-(2,2
      dimethylpropane-1,3-dyl)bis(azanylylidene)bis(methanylylidene)diphenol), from 2,2
      dimethyl-1,3-diaminopropane and its reaction with UO2(CH3COO)2.2H2O in a 1:1
      molar ratio in methanol to produce the complex [UO2(L)(CH3OH)] are reported. The
      isolated compounds have been characterized by elemental analysis, ionization mass
      spectrometry (ESI-MS), UV/Vis, FT-IR, (1)H- and (13)C-NMR, DEPT-135 spectroscopy,
      TGA and single-crystal X-ray diffraction. As shown by X-ray crystallography, the
      coordination geometry around the uranium centre is distorted pentagonal
      bipyramidal with two imine nitrogen atoms, two phenolic oxygen atoms and one
      methanol O atom occupying equatorial sites, together with two axial oxo groups.
      To obtain insights into the structure and spectral properties of the studied
      complex, density functional theory (DFT) and time dependent density functional
      theory (TD-DFT) calculations have been carried out. The computed results show
      that LUMO of the complex is featured with uranium f orbital character. TD-DFT
      results indicate that the complex displays two intense bands and one weak charge
      transfer band. The charge transfer band is primarily due to HOMO -> LUMO (53%).
      Two intense bands have main contributions from HOMO-2 -> LUMO (81%) and HOMO-3 ->
      LUMO (77%) transitions, respectively. TD-DFT results indicate that the complex
      displays the charge transfer band primarily due to HOMO -> LUMO (53%) and other
      two charge transfer bands have main contributions from HOMO-2 -> LUMO (81%), HOMO
      3 -> LUMO (77%) transitions, respectively. NBO analysis reveals that the ground
      state of the complex is mainly stabilized by n->n* interaction. EDA analysis
      reveals that the interaction existing between the ligand and other parts of the
      complex is mainly electrostatic in nature.

PMID- 25380388
TI  - Cervical spondylotic myelopathy caused by single-level vertebral spontaneous
      fusion.
AB  - PURPOSE: To evaluate the clinical features, imaging characteristics, surgical
      options, and clinical outcomes of patients with Cervical spondylotic myelopathy
      (CSM) caused by single-level vertebral spontaneous fusion (SLVSF). METHODS:
      Sixteen consecutive patients with SLVSF who underwent anterior surgery were
      included in this study and 38 patients with CSM caused by spinal degeneration
      were enrolled as a control group. Demographic features, clinical presentations,
      imaging characteristics, surgery strategy, Nurick grade, Japanese Orthopedic
      Association (JOA) score, neck disability index (NDI), and complications were
      evaluated. RESULTS: There were significant differences between the two groups in
      the mean age and the average duration of neck pain. There was no significant
      difference between the two groups in length of cervical spine. In the SLVSF
      group, 13 patients had upper segment translational instability and none had
      rotational instability. Pre- and postoperative Nurick grades were 2.94+/-0.77 and
      2.19+/-0.54 in the SLVSF group, and 2.97+/-0.72 and 2.16+/-0.64 in the control
      group. Pre- and postoperative JOA scores were 9.25+/-2.02 and 11.69+/-1.62 in the
      SLVSF group, and 9.87+/-2.58 and 12.53+/-2.69 in the control group. Pre- and
      postoperative NDI values were 28.5+/-7.75 and 15.56+/-5.51 in the SLVSF group,
      and 16+/-6.13 and 11.29+/-4.58 in the control group. CONCLUSIONS: Patients with
      SLVSF have necks of normal lengths, which can be used to distinguish this
      disorder from Klippel-Feil syndrome. There are three main features of SLVSF: (1)
      hypoplasia at both of the spontaneously fused vertebral bodies; (2) a major
      pathological feature of translational instability of the upper vertebra to the
      fused level; and (3) severe neck pain. Anterior surgery has a good therapeutic
      effect for patients with cervical SLVSF.

PMID- 25380391
TI  - Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in
      diabetic rats.
AB  - This study was designed to investigate the effects of mangiferin on renal
      fibrosis, osteopontin production, and inflammation in the kidney of diabetic
      rats. Diabetes was induced through the single administration of streptozotocin
      (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60
      mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus
      fibrosis examination using Masson trichrome staining. Kidney and blood were
      obtained for assays of the associated biochemical parameters. Chronic mangiferin
      treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason
      stained positive area of glomeruli, protein expression of type IV collagen, and
      alpha-smooth muscle actin in the kidney of diabetic rats, in comparison with
      decreases in mRNA and protein expression of osteopontin as well as protein
      expression of cyclooxygenase 2 and NF-kB p65 subunit in the renal cortex of
      diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1beta in
      both the serum and the kidney of diabetic rats. Our findings demonstrate that
      mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is
      realized through the suppression of osteopontin overproduction and inflammation
      likely via inactivation of NF-kB.

PMID- 25380392
TI  - Dynamics of lipids, cholesterol, and transmembrane alpha-helices from microsecond
      molecular dynamics simulations.
AB  - Extensive all-atom molecular dynamics (~24 MUs total) allowed exploration of
      configurational space and calculation of lateral diffusion coefficients of the
      components of a protein-embedded, cholesterol-containing model bilayer. The three
      model membranes are composed of an ~50/50 (by mole)
      dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayer and contained an alpha
      helical transmembrane protein (HIV-1 gp41 TM). Despite the high concentration of
      cholesterol, normal Brownian motion was observed and the calculated diffusion
      coefficients (on the order of 10(-9) cm(2)/s) are consistent with experiments.
      Diffusion is sensitive to a variety of parameters, and a temperature difference
      of ~4 K from thermostat artifacts resulted in 2-10-fold differences in diffusion
      coefficients and significant differences in lipid order, membrane thickness, and
      unit cell area. Also, the specific peptide sequence likely underlies the
      consistently observed faster diffusion in one leaflet. Although the simulations
      here present molecular dynamics (MD) an order of magnitude longer than those from
      previous studies, the three systems did not approach ergodicity. The
      distributions of cholesterol and DPPC around the peptides changed on the
      microsecond time scale, but not significantly enough to thoroughly explore
      configurational space. These simulations support conclusions of other recent
      microsecond MD in that even longer time scales are needed for equilibration of
      model membranes and simulations of more realistic cellular or viral bilayers. 

PMID- 25380390
TI  - Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate
      cancer stem/progenitor cells.
AB  - Cancer stem cells (CSCs), including those of advanced prostate cancer, are a
      suggested reason for tumor resistance toward conventional tumor therapy.
      Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite
      the minimal understanding of their modes of action, natural products and herbal
      therapies have been commonly used in the prevention and treatment of many
      cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may
      possess anti-cancer activity and a high potential for eliminating CSCs. We tested
      the effect of BLE on prostate cancer cells and our data indicated that this
      extract induced significant reduction in cell viability and inhibited the
      proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a
      dose- and time-dependent manner. BLE extract induced a perturbation of the cell
      cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death,
      characterized by the production of high levels of reactive oxidative species
      (ROS). Inhibition of cellular migration and invasion was also achieved upon
      treatment with BLE extract, suggesting a role in inhibiting metastasis.
      Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D
      sphere-formation assay to enrich for a population of cancer stem/progenitor
      cells. Our results showed a significant reduction in sphere formation ability.
      Three rounds of treatment with BLE extract were sufficient to eradicate the self
      renewal ability of highly resistant CSCs. In conclusion, our results suggest a
      high therapeutic potential of BLE extract in targeting prostate cancer and its
      CSCs. 

PMID- 25380393
TI  - Active and selective conversion of CO2 to CO on ultrathin Au nanowires.
AB  - In this communication, we show that ultrathin Au nanowires (NWs) with dominant
      edge sites on their surface are active and selective for electrochemical
      reduction of CO2 to CO. We first develop a facile seed-mediated growth method to
      synthesize these ultrathin (2 nm wide) Au NWs in high yield (95%) by reducing
      HAuCl4 in the presence of 2 nm Au nanoparticles (NPs). These NWs catalyze CO2
      reduction to CO in aqueous 0.5 M KHCO3 at an onset potential of -0.2 V (vs
      reversible hydrogen electrode). At -0.35 V, the reduction Faradaic efficiency
      (FE) reaches 94% (mass activity 1.84 A/g Au) and stays at this level for 6 h
      without any noticeable activity change. Density functional theory (DFT)
      calculations suggest that the excellent catalytic performance of these Au NWs is
      attributed both to their high mass density of reactive edge sites (>=16%) and to
      the weak CO binding on these sites. These ultrathin Au NWs are the most efficient
      nanocatalyst ever reported for electrochemical reduction of CO2 to CO. 

PMID- 25380394
TI  - A systematic review of the prevalence of mildly abnormal liver function tests and
      associated health outcomes.
AB  - Liver function tests (LFTs) are commonly performed to investigate asymptomatic
      individuals or those with nonspecific symptoms. Understanding the prevalence of
      mildly abnormal LFTs in the general population and the prevalence of liver
      disease following abnormal LFTs has important implications for the planning of
      care pathways and the provision of healthcare services. A systematic review of
      the literature on the prevalence of abnormal LFTs in the general population and
      their respective health outcomes was conducted. A total of 37 studies reporting
      data on the prevalence of abnormal LFTs (published between 2000 and 2014) were
      identified from online database searches or were manually selected from article
      bibliographies. The prevalence of mildly abnormal LFTs, with one or more abnormal
      constituents in the LFT, was high at 10-21.7%. The prevalence of severe liver
      disease within cohorts with abnormal LFTs is relatively low (<5%), and a large
      proportion of abnormal LFTs remains unexplained. Among individuals with
      unexplained abnormal LFTs, risk factors include obesity and insulin resistance.
      Common aetiologies for abnormal LFTs were non-alcohol-related fatty liver disease
      (NAFLD), followed by alcohol use and viral infections. In addition, normal LFTs
      do not rule out liver disease. The prevalence of abnormal LFTs depends on the
      definition and population but is likely to be between 10 and 20% in the general
      population. Abnormal LFTs are associated with a range of health outcomes but are
      not necessarily strongly diagnostic of severe liver pathology. Important areas of
      future research include further studies on the prevalence and predictive ability
      of LFTs in large, population-representative samples. 

PMID- 25380397
TI  - Simple synthesis and photoelectrochemical characterizations of
      polythiophene/Pd/TiO2 composite microspheres.
AB  - We report here a simple, effective, and low cost method to synthesize
      polythiophene/Pd/TiO2 (PTh/Pd/TiO2) ternary composite microspheres and apply such
      a composite to photoelectrochemical (PEC) sensing. TiO2 spherical aggregates of
      200 nm diameter, consisting of nanoscale building blocks of TiO2, have been
      prepared by hydrolysis of tetrabutyl titanate in a water-in-oil emulsion system
      (Vwater/Vacetone=1/100). Pd species and PTh layer were decorated onto TiO2
      microspherical substrates by reduction of Pd salts and polymerization of
      thiophene, respectively. The high surface area, effective charge transfer, and
      enhanced light absorption of the ternary composite could improve PEC performance
      under simulated sunlight. The sensitivity, selectivity, and stability of PEC
      sensor for detecting l-cysteine were much higher than those of the traditional
      electrochemical sensor. The detection limit of l-cysteine was 9.24 MUM in the
      linear range of 0.31-5.30 mM. Moreover, the results also indicated a good anti
      interference and acceptable accuracy in practical application, providing a rapid
      and sensitive detection method.

PMID- 25380398
TI  - Ruthenium-catalyzed redox-neutral C-H activation via N-N cleavage: synthesis of N
      substituted indoles.
AB  - The first Ru-catalyzed redox-neutral C-H activation reaction via N-N bond
      cleavage is reported. Pyrazolidin-3-one is demonstrated as an internally
      oxidative directing group that enables C-H annulation reactions with a broad
      scope of alkynes, including previously incompetent terminal alkynes.
      Pharmacologically privileged 3-(1H-indol-1-yl)propanamides were synthesized in
      high yields. 

PMID- 25380396
TI  - Solution formulation development and efficacy of MJC13 in a preclinical model of
      castration-resistant prostate cancer.
AB  - MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of
      castration-resistant prostate cancer. The purpose of this work was to develop a
      solution formulation of MJC13, and obtain its efficacy profile in a human
      prostate cancer xenograft mouse model. Preformulation studies were conducted to
      evaluate the physicochemical properties. Co-solvent systems were evaluated for
      aqueous solubility and tolerance. A human prostate cancer xenograft mouse model
      was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The
      optimal formulation was used to study the efficacy of MJC13 in this preclinical
      model of castrate-resistant prostate cancer. We found that MJC13 was stable (at
      least for 1 month), highly lipophilic (logP = 6.49), poorly soluble in water
      (0.28 ug/mL), and highly plasma protein bound (>98%). The optimal formulation
      consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13
      concentration of 7.5 mg/mL, and tolerated an aqueous environment. After twice
      weekly intratumoral injection with 10 mg/kg MJC13 in this formulation for four
      consecutive weeks, tumor volumes were significantly reduced compared to vehicle
      treated controls. 

PMID- 25380399
TI  - Physical activity and psychiatric symptoms in adults with schizophrenia spectrum
      disorders.
AB  - People diagnosed with schizophrenia spectrum disorders (SSDs) experience
      significant health disparity due to cardiovascular disease. One key to
      cardiovascular health is physical activity (PA). In addition, sedentary behavior
      is recognized as a health threat, independent of PA levels. The current study
      sought to identify the relationship of psychiatric symptoms of SSD to measured PA
      and sedentary behavior. Findings indicated that less than half of the sample
      obtained the recommended minutes of moderate-to-vigorous PA (MVPA) per week.
      Subjects who were younger and had greater cognitive disorganization engaged in
      more minutes of MVPA. In contrast, sedentary behavior was only associated with
      aspects of metacognitive functioning, such that subjects who had greater ability
      for forming integrated representations of themselves and the related capacity to
      use knowledge of themselves spent less time in sedentary behaviors. This study
      expands upon the limited literature available on individuals with SSD and PA
      levels. 

PMID- 25380400
TI  - Impacts of ionic strength on three-dimensional nanoparticle aggregate structure
      and consequences for environmental transport and deposition.
AB  - The transport of nanoparticles through aqueous systems is a complex process with
      important environmental policy ramifications. Ferrihydrite nanoparticles commonly
      form aggregates, with structures that depend upon solution chemistry. The impact
      of aggregation state on transport and deposition is not fully understood. In this
      study, small-angle X-ray scattering (SAXS) and cryogenic transmission electron
      microscopy (cryo-TEM) were used to directly observe the aggregate structure of
      ferrihydrite nanoparticles and show how the aggregate structure responds to
      changing ionic strength. These results were correlated with complementary studies
      on ferrihydrite transport through saturated quartz sand columns. Within deionized
      water, nanoparticles form stable suspensions of low-density fractal aggregates
      that are resistant to collapse. The particles subsequently show limited
      deposition on sand grain surfaces. Within sodium nitrate solutions the aggregates
      collapse into denser clusters, and nanoparticle deposition increases dramatically
      by forming thick, localized, and mechanically unstable deposits. Such deposits
      limit nanoparticle transport and make transport less predictable. The action of
      ionic strength is distinct from simpler models of colloidal stability and
      transport, in that salt not only drives aggregation or attachment but also alters
      the behavior of preexisting aggregates by triggering their collapse. 

PMID- 25380402
TI  - Polymer-nanocomposite brush-like architectures as an all-solid electrolyte
      matrix.
AB  - Herein, we report on polymer-nanocomposites with brush-like architectures and
      evaluate their feasibility as an all-solid electrolyte matrix supporting Li(+)
      ion conduction. Showcased as a first example in the domain of electrolyte
      research, the study probes several key factors, such as (i) core morphology, (ii)
      surface modifiers/functionality, (iii) grafting length, and (iv) density of the
      brushes, and determines their role on the overall electrochemical properties of
      these nanostructured organic-inorganic hybrids. Nanostructured titania was
      synthesized via wet-chemical approaches using either controlled hydrolysis or
      hydrothermal methods. Exercising suitable control on reaction parameters led to
      well-defined morphologies/phases, such as nanoparticles, nanospindles,
      nanourchins, nanorods or nanotubes, in either anatase, rutile or mixed forms.
      Covalent anchoring on titania nanostructures was achieved using dopamine, gallic
      acid and glycerol as small organic moieties. A one-pot process of priming the
      available surface functional groups postmodification with isocyanate chemistry
      was followed by grafting polyethylene glycol monomethyl ethers of desired chain
      lengths. Finally, complexation with lithium salt yielded electrolyte compositions
      where the ethylene oxide (EO) fractions aid in ion-solvation with ease. The
      synthesized materials were characterized in detail employing XRD, TEM, DRS-UV,
      FTIR, micro-Raman, TG-DTA and DSC at each stage to confirm the products and
      ascertain the physicochemical properties. Comprehensive evaluation using
      temperature-step electrochemical impedance spectroscopy (EIS) of these brush-like
      nanocomposites provided crucial leads toward establishing a plausible physical
      model for the system and understanding the mechanism of ion transport in these
      all-solid matrices. The preliminary results on ionic conductivity (sigma)
      obtained for some of the compositions are estimated to be within the range of
      ~10(-4) to 10(-5) S cm(-1) in the temperature window of the study that holds
      excellent promise for further improvement. 

PMID- 25380401
TI  - Spatial and temporal variations of crop fertilization and soil fertility in the
      loess plateau in china from the 1970s to the 2000s.
AB  - Increased fertilizer input in agricultural systems during the last few decades
      has resulted in large yield increases, but also in environmental problems. We
      used data from published papers and a soil testing and fertilization project in
      Shaanxi province during the years 2005 to 2009 to analyze chemical fertilizer
      inputs and yields of wheat (Triticum aestivum L.) and maize (Zea mays L.) on the
      farmers' level, and soil fertility change from the 1970s to the 2000s in the
      Loess Plateau in China. The results showed that in different regions of the
      province, chemical fertilizer NPK inputs and yields of wheat and maize increased.
      With regard to soil nutrient balance, N and P gradually changed from deficit to
      surplus levels, while K deficiency became more severe. In addition, soil organic
      matter, total nitrogen, alkali-hydrolysis nitrogen, available phosphorus and
      available potassium increased during the same period. The PFP of N, NP and NPK on
      wheat and maize all decreased from the 1970s to the 2000s as a whole. With the
      increase in N fertilizer inputs, both soil total nitrogen and alkali-hydrolysis
      nitrogen increased; P fertilizer increased soil available phosphorus and K
      fertilizer increased soil available potassium. At the same time, soil organic
      matter, total nitrogen, alkali-hydrolysis nitrogen, available phosphorus and
      available potassium all had positive impacts on crop yields. In order to promote
      food safety and environmental protection, fertilizer requirements should be
      assessed at the farmers' level. In many cases, farmers should be encouraged to
      reduce nitrogen and phosphate fertilizer inputs significantly, but increase
      potassium fertilizer and organic manure on cereal crops as a whole. 

PMID- 25380403
TI  - Generalizing attentional control across dimensions and tasks: evidence from
      transfer of proportion-congruent effects.
AB  - Three experiments investigated transfer of list-wide proportion congruent (LWPC)
      effects from a set of congruent and incongruent items with different frequency
      (inducer task) to a set of congruent and incongruent items with equal frequency
      (diagnostic task). Experiments 1 and 2 mixed items from horizontal and vertical
      Simon tasks. Tasks always involved different stimuli that varied on the same
      dimension (colour) in Experiment 1 and on different dimensions (colour, shape) in
      Experiment 2. Experiment 3 mixed trials from a manual Simon task with trials from
      a vocal Stroop task, with colour being the relevant stimulus in both tasks. There
      were two major results. First, we observed transfer of LWPC effects in
      Experiments 1 and 3, when tasks shared the relevant dimension, but not in
      Experiment 2. Second, sequential modulations of congruency effects transferred in
      Experiment 1 only. Hence, the different transfer patterns suggest that LWPC
      effects and sequential modulations arise from different mechanisms. Moreover, the
      observation of transfer supports an account of LWPC effects in terms of list-wide
      cognitive control, while being at odds with accounts in terms of stimulus
      response (contingency) learning and item-specific control. 

PMID- 25380404
TI  - Pd(II)-catalyzed C-H arylation of aryl and benzyl Weinreb amides.
AB  - The first example of palladium-catalyzed ortho-C-H arylation of aryl and benzyl
      Weinreb amides was developed, in which HOTf was used as a key promoter. This
      method exhibits good functional group tolerance, a broad substrate scope of both
      Weinreb amides and aryl iodides, high mono-selectivity and mild reaction
      conditions. 

PMID- 25380405
TI  - Effect of therapeutic hypothermia on C-reactive protein levels in patients with
      perinatal asphyxia.
AB  - OBJECTIVE: To determine the changes in serum C-reactive protein (CRP) levels
      during therapeutic hypothermia. STUDY DESIGN: Between January 2011 and June 2013,
      133 hypoxic-ischemic encephalopathy patients being followed up in the neonatal
      intensive care unit of Dr. Sami Ulus Maternity and Children's Hospital are
      prospectively evaluated. Group 1; patients that received therapeutic hypothermia
      (n = 74) and group 2; patients that did not required therapeutic hypothermia (n =
      59). All the patients underwent serial complete blood cell count and CRP
      assessments; blood cultures were obtained from all the cases at the time of
      admission and when CRP levels were elevated. RESULTS: Positive blood cultures
      were encountered in five cases (6.7%) in group 1 while no blood culture-proven
      septicemia was encountered in group 2. The CRP levels elevated gradually reaching
      a peak level on the 4th day and then decreased during the therapeutic hypothermia
      in patients with no blood culture-proven septicemia in group 1. The CRP levels
      showed statistically significant changes reaching a peak level on the 7th day in
      patients with blood culture-proven septicemia in group 2. Also, the CRP levels
      showed no alteration with time in group 2. CONCLUSION: Therapeutic hypothermia
      itself might be associated with CRP elevation rather than an actual infection.

PMID- 25380406
TI  - Transseptal puncture to facilitate device closure of "long-tunnel" patent foramen
      ovale.
AB  - BACKGROUND: Patent foramen ovale (PFO) is common and may predispose to
      paradoxical embolism. Transcatheter device closure of PFO can be challenging in
      certain cases of "long-tunnel" PFO morphology. We report our experience with
      device closure of long-tunnel PFO using transseptal puncture. METHODS: We
      retrospectively reviewed all cases of PFO device closure using transseptal
      puncture at the Mayo Clinic from January 1, 2010 to September 30, 2013. We
      arbitrarily defined a PFO tunnel configuration as a tunnel length >= 12 mm as
      observed in intracardiac echocardiography (ICE) at the time of device closure.
      RESULTS: Twelve patients (mean age 40.8 [range 15-67] years; 7 males [58%])
      underwent PFO device closure with transseptal puncture. The most common
      indication for PFO closure was previous stroke (n = 7, 58%). Median tunnel length
      measured by ICE was 15 mm (12-20 mm). GORE(r) HELEX(r) Septal Occluder was used
      for closure in all but one patient. The only significant procedural complication
      was a minor perforation of the left atrial wall during attempted septal puncture,
      which resulted in a trivial pericardial effusion that resolved without
      intervention. At latest follow-up (mean 543 days, [range 170-1162]) one patient
      had a residual shunt and subsequently died due to complications during surgical
      PFO closure. No recurrent strokes or TIAs were reported. CONCLUSION: Though not
      without risk, transseptal puncture can be a valuable tool for facilitating device
      closure of long-tunnel type PFOs. GORE(r) HELEX(r) Septal Occluder may be an
      effective option for facilitating device closure for patients with long-tunnel
      type PFO.

PMID- 25380407
TI  - Porous aromatic frameworks impregnated with fullerenes for enhanced
      methanol/water separation.
AB  - Molecular simulation techniques have revealed that the incorporation of
      fullerenes within porous aromatic frameworks (PAFs) remarkably enhances methanol
      uptake while inhibiting water uptake. The highest selectivity of methanol over
      water is found to be 1540 at low pressure (1 kPa) and decreases gradually with
      increasing pressure. The adsorption of water is very small compared to methanol,
      a useful material property for membrane and adsorbent-based separations. Grand
      canonical Monte Carlo (GCMC) simulations are utilized to calculate the pure
      component and mixture adsorption isotherms. The water and methanol mixture
      simulations show that water uptake is further inhibited above the pure component
      results because of the dominant methanol adsorption. Molecular dynamics (MD)
      simulations confirm that water diffusivity is also inhibited by strong methanol
      adsorption in the mixture. Overall, this study reveals profound hydrophobicity in
      C60@PAF materials and recommends C60@PAFs as suitable applicants for adsorbent
      and membrane-based separations of methanol/water mixtures and other alcohol/water
      separation applications. 

PMID- 25380408
TI  - Postoperative cystogram findings predict incontinence following robot-assisted
      radical prostatectomy.
AB  - INTRODUCTION: The factors that contribute to continence following robot-assisted
      radical prostatectomy (RARP) are currently being investigated. The purpose of
      this study is to determine the relationship of the bladder neck location on
      postoperative cystogram to subsequent continence rates following RARP. PATIENTS
      AND METHODS: A retrospective review of 611 consecutive RARP patients identified
      215 patients with a postoperative cystogram. A ratio was created by measuring the
      distance from the superior edge of the pubic symphysis to the bladder neck and
      dividing it by the total pubic symphysis height, termed the bladder neck to pubic
      symphysis (BNPS) ratio. Odds ratios with 95% confidence intervals (CI) were
      calculated for the relationship between incontinence and BNPS tertile categories.
      RESULTS: At 3-month follow-up, continent patients had a mean BNPS ratio of 0.39
      (95% CI 0.35, 0.43), while incontinent patients had a mean BNPS ratio of 0.49
      (95% CI 0.42, 0.56; p=0.01). At 12 months, the mean BNPS ratio was 0.40 (95% CI
      0.37, 0.44) for continent patients, whereas incontinent patients had a mean BNPS
      ratio of 0.60 (95% CI 0.43, 0.77; p=0.001). When analyzed as tertile groups, the
      corresponding incontinence rates at 12 months were 2.8%, 2.8%, and 19.4% for the
      lowest, middle, and highest BNPS tertiles, respectively. CONCLUSIONS:
      Postprostatectomy bladder neck location defined by the BNPS ratio on cystogram
      correlates with continence rates and may predict patients at risk for prolonged
      incontinence. Efforts designed to preserve support of the bladder neck and
      sphincteric complex in relation to the pubic symphysis may improve both early and
      late continence.

PMID- 25380409
TI  - First-principles study of ground-state properties of U2Mo.
AB  - By means of first-principles calculations, we have systematically investigated
      the structural, elastic, vibrational, thermal and electronic properties of the
      ground-state phase for the intermetallic compound U2Mo. Our results reveal that
      the previously synthesized I4/mmm structure of U2Mo is a metastable phase and
      unstable, neither thermodynamically nor vibrationally at the ground state. In
      combination with the evolutionary structural searches, our first-principles
      calculations suggest a new ground-state Pmmn phase, which has been confirmed
      theoretically to be stable, both thermodynamically and vibrationally. Moreover,
      through the DFT + D technique we have discussed the influence of van der Waals
      interactions on the structural, elastic and vibrational properties, revealing a
      weak effect in pure U and Mo solids and U2Mo alloy. The analysis of the
      electronic band structures evidences its electronic stabilities with the
      appearance of a deep valley in the density of states at the Fermi level.
      Moreover, we have investigated further the temperature-dependent structural,
      thermal expansion and elastic properties of our proposed Pmmn ground-state phase.
      These results are expected to stimulate further experimental investigations of
      the ground-state phase of U2Mo. 

PMID- 25380410
TI  - Copper-catalyzed enantioselective 1,4-addition of alkyl groups to N-sulfonyl
      imines.
AB  - In copper(I)/phosphoramidite-catalyzed asymmetric 1,4-additions of dialkylzinc, N
      sulfonyl imines are more reactive and furnish higher enantiomeric excesses than
      the respective cycloalk-2-enones. This enables formation of a quaternary
      stereocenter as well as a cis-selective addition to an imine derived from 5
      methylcyclohex-2-enone. The 1,4-adducts can be transformed in stereodivergent
      reductions yielding cis- or trans-3-alkylcycloalkyl amides.

PMID- 25380411
TI  - Synthesis of strongly fluorescent molybdenum disulfide nanosheets for cell
      targeted labeling.
AB  - MoS2 nanosheets with polydispersity of the lateral dimensions from natural
      mineral molybdenite have been prepared in the emulsions microenvironment built by
      the water/surfactant/CO2 system. The size, thickness, and atomic structure are
      characterized by transmission electron microscopy (TEM), atomic force microscopy
      (AFM), and laser-scattering particle size analysis. Meanwhile, by the analysis of
      photoluminescence spectroscopy and microscope, the MoS2 nanosheets with smaller
      lateral dimensions exhibit extraordinary photoluminescence properties different
      from those with relatively larger lateral dimensions. The discovery of the
      excitation dependent photoluminescence for MoS2 nanosheets makes them potentially
      of interests for the applications in optoelectronics and biology. Moreover, we
      demonstrate that the fabricated MoS2 nanosheets can be a nontoxic fluorescent
      label for cell-targeted labeling application. 

PMID- 25380412
TI  - Discovery and optimization of an azetidine chemical series as a free fatty acid
      receptor 2 (FFA2) antagonist: from hit to clinic.
AB  - FFA2, also called GPR43, is a G-protein coupled receptor for short chain fatty
      acids which is involved in the mediation of inflammatory responses. A class of
      azetidines was developed as potent FFA2 antagonists. Multiparametric optimization
      of early hits with moderate potency and suboptimal ADME properties led to the
      identification of several compounds with nanomolar potency on the receptor
      combined with excellent pharmacokinetic (PK) parameters. The most advanced
      compound, 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]
      (3-chloro-benzyl)-amino]-butyric acid 99 (GLPG0974), is able to inhibit acetate
      induced neutrophil migration strongly in vitro and demonstrated ability to
      inhibit a neutrophil-based pharmacodynamic (PD) marker, CD11b activation-specific
      epitope [AE], in a human whole blood assay. All together, these data supported
      the progression of 99 toward next phases, becoming the first FFA2 antagonist to
      reach the clinic. 

PMID- 25380413
TI  - No effects of hydrocortisone and dexamethasone on pain sensitivity in healthy
      individuals.
AB  - BACKGROUND: There is some evidence that stress-induced cortisol increase leads to
      a decrease in pain, while lowering cortisol levels enhances pain sensitivity, but
      no study has yet investigated both pharmacological enhancement and reduction of
      cortisol levels in the same individuals. METHODS: Firstly, we tested in 16
      healthy individuals whether the treatment with hydrocortisone and dexamethasone,
      respectively, results in altered pain thresholds. Secondly, we aimed to test
      whether hormone effects are different across the pain range by using ratings for
      pain stimuli with varying intensity; and thirdly, we tested whether cortisol
      levels influence the discrimination ability for painful stimuli. RESULTS: Despite
      substantial effects of dexamethasone and hydrocortisone administration on
      cortisol levels, no effect of these drugs was seen in terms of pain sensitivity
      (pain threshold, pain rating, pain discrimination ability), although
      comprehensively examined. However, in the placebo condition, a significant
      negative correlation between cortisol and pain thresholds was seen. Similarly,
      there were also strong negative associations between cortisol levels in the
      placebo condition and pain thresholds after drug treatment (especially after
      hydrocortisone). CONCLUSION: These findings suggest that short-term variations of
      cortisol do not influence pain sensitivity whereas, in general, high levels of
      cortisol are associated with increased pain sensitivity, at least for weak to
      moderate stimuli.

PMID- 25380415
TI  - Profiling of esterified fatty acids as biomarkers in the blood of dengue fever
      patients using a microliter-scale extraction followed by gas chromatography and
      mass spectrometry.
AB  - An improved gas chromatography with mass spectrometry procedure was developed to
      highlight the esterified fatty acids in 100 MUL blood of dengue fever patients in
      the early febrile phase versus healthy volunteers. 24 adult patients and 24
      healthy volunteers were included in this study. The recoveries of targeted
      esterified fatty acids content were in the range of 92.10-101.00% using
      methanol/dichloromethane (2:1, v/v) as the extraction solvent. An efficient
      chromatographic separation of targeted 17 esterified fatty acid methyl esters was
      obtained. The limits of detection and quantification were within the range of 16
      131 and 53-430 ng/mL, respectively. The relative standard deviation of intraday
      and interday precision values ranged from 0.4 to 5.0%. The statistical data
      treatment showed a significant decrease of the content of four saturated fatty
      acids, C14:0, C15:0, C16:0, and C18:0 (P value < 0.05), and also showed a
      decrease of the content of eight unsaturated fatty acids, C16:1, C18:3n6,
      C18:2n6, C18:1n9, C20:3n3, C20:4n6, C20:2, and C22:6n3 (P value < 0.05) in dengue
      fever patients. Moreover, the amount of three omega-6 fatty acids including
      C18:3n6, C18:2n6, and C20:4n6 was dramatically decreased in the blood of dengue
      fever patients to a limit of 50 +/- 10%. 

PMID- 25380414
TI  - Tissue-engineered heart valve with a tubular leaflet design for minimally
      invasive transcatheter implantation.
AB  - Transcatheter aortic valve implantation of (nonviable) bioprosthetic valves has
      been proven a valid alternative to conventional surgical implantation in patients
      at high or prohibitive mortality risk. In this study we present the in vitro
      proof-of-principle of a newly developed tissue-engineered heart valve for
      minimally invasive implantation, with the ultimate aim of adding the unique
      advantages of a living tissue with regeneration capabilities to the continuously
      developing transcatheter technologies. The tube-in-stent is a fibrin-based tissue
      engineered valve with a tubular leaflet design. It consists of a tubular
      construct sewn into a self-expandable nitinol stent at three commissural
      attachment points and along a circumferential line so that it forms three
      coaptating leaflets by collapsing under diastolic back pressure. The tubular
      constructs were molded with fibrin and human umbilical vein cells. After 3 weeks
      of conditioning in a bioreactor, the valves were fully functional with
      unobstructed opening (systolic phase) and complete closure (diastolic phase).
      Tissue analysis showed a homogeneous cell distribution throughout the valve's
      thickness and deposition of collagen types I and III oriented along the
      longitudinal direction. Immunohistochemical staining against CD31 and scanning
      electron microscopy revealed a confluent endothelial cell layer on the surface of
      the valves. After harvesting, the valves underwent crimping for 20 min to
      simulate the catheter-based delivery. This procedure did not affect the valvular
      functionality in terms of orifice area during systole and complete closure during
      diastole. No influence on the extracellular matrix organization, as assessed by
      immunohistochemistry, nor on the mechanical properties was observed. These
      results show the potential of combining tissue engineering and minimally invasive
      implantation technology to obtain a living heart valve with a simple and robust
      tubular design for transcatheter delivery. The effect of the in vivo remodeling
      on the functionality of the tube-in-stent valve remains to be tested.

PMID- 25380416
TI  - Changes in air quality and tropospheric composition due to depletion of
      stratospheric ozone and interactions with changing climate: implications for
      human and environmental health.
AB  - UV radiation is an essential driver for the formation of photochemical smog,
      which includes ground-level ozone and particulate matter (PM). Recent analyses
      support earlier work showing that poor outdoor air quality is a major
      environmental hazard as well as quantifying health effects on regional and global
      scales more accurately. Greater exposure to these pollutants has been linked to
      increased risks of cardiovascular and respiratory diseases in humans and is
      associated globally with several million premature deaths per year. Ozone also
      has adverse effects on yields of crops, leading to loss of billions of US dollars
      each year. These detrimental effects also may alter biological diversity and
      affect the function of natural ecosystems. Future air quality will depend mostly
      on changes in emission of pollutants and their precursors, but changes in UV
      radiation and climate will contribute as well. Significant reductions in
      emissions, mainly from the energy and transportation sectors, have already led to
      improved air quality in many locations. Air quality will continue to improve in
      those cities/states that can afford controls, and worsen where the regulatory
      infrastructure is not available. Future changes in UV radiation and climate will
      alter the rates of formation of ground-level ozone and photochemically-generated
      particulate matter and must be considered in predictions of air quality. The
      decrease in UV radiation associated with recovery of stratospheric ozone will,
      according to recent global atmospheric model simulations, lead to increases in
      ground-level ozone at most locations. If correct, this will add significantly to
      future ground-level ozone trends. However, the spatial resolution of these global
      models is insufficient to inform policy at this time, especially for urban areas.
      UV radiation affects the atmospheric concentration of hydroxyl radicals, OH,
      which are responsible for the self-cleaning of the atmosphere. Recent
      measurements confirm that, on a local scale, OH radicals respond rapidly to
      changes in UV radiation. However, on large (global) scales, models differ in
      their predictions by nearly a factor of two, with consequent uncertainties for
      estimating the atmospheric lifetime and concentrations of key greenhouse gases
      and air pollutants. Projections of future climate need to consider these
      uncertainties. No new negative environmental effects of substitutes for ozone
      depleting substances or their breakdown-products have been identified. However,
      some substitutes for the ozone depleting substances will continue to contribute
      to global climate change if concentrations rise above current levels. 

PMID- 25380418
TI  - Asymmetric effects of low doses of progesterone on GABA(A) receptor alpha4
      subunit protein expression in the olfactory bulb of female rats.
AB  - The aim of this study was to evaluate the effect of progesterone on the protein
      expression of alpha4 subunit of GABA(A) receptor, serotonin transporter (SERT),
      Akt, Erk, and caspase-3 in the olfactory bulb (OB) of female rats exposed to the
      forced swimming test (FST). Female rats were injected daily with progesterone
      (0.4 mg/kg body mass) or vehicle during 2 complete oestrous cycles and exposed to
      the FST, and the protein expression of GABA(A) receptor alpha4 subunit, SERT,
      Akt, Erk, and caspase-3 in the OB were evaluated. Progesterone increased the
      expression of the alpha4 subunit in the right OB and decreased its expression in
      the left OB, although it did not change the expression of other proteins. In
      summary, our findings indicate that progesterone has an asymmetric modulatory
      effect on the expression of GABA(A) receptor alpha4 subunit in the OB. This
      effect could be related to the antidepressant-like effect of progesterone in
      female rats. 

PMID- 25380419
TI  - Outpaced by an outbreak.

PMID- 25380420
TI  - Landmark approvals in idiopathic pulmonary fibrosis.

PMID- 25380421
TI  - Takeda's second bet on DARTs.

PMID- 25380417
TI  - Connectivity of pacemaker neurons in the neonatal rat superficial dorsal horn.
AB  - Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing
      have been characterized in lamina I of the neonatal spinal cord, where they are
      innervated by high-threshold sensory afferents. However, little is known about
      the output of these pacemakers, as the neuronal populations that are targeted by
      pacemaker axons have yet to be identified. The present study combines patch-clamp
      recordings in the intact neonatal rat spinal cord with tract-tracing to
      demonstrate that lamina I pacemaker neurons contact multiple spinal motor
      pathways during early life. Retrograde labeling of premotor interneurons with the
      trans-synaptic pseudorabies virus PRV-152 revealed the presence of burst-firing
      in PRV-infected lamina I neurons, thereby confirming that pacemakers are
      synaptically coupled to motor networks in the spinal ventral horn. Notably, two
      classes of pacemakers could be distinguished in lamina I based on cell size and
      the pattern of their axonal projections. Whereas small pacemaker neurons
      possessed ramified axons that contacted ipsilateral motor circuits, large
      pacemaker neurons had unbranched axons that crossed the midline and ascended
      rostrally in the contralateral white matter. Recordings from identified spino
      parabrachial and spino-periaqueductal gray neurons indicated the presence of
      pacemaker activity within neonatal lamina I projection neurons. Overall, these
      results show that lamina I pacemakers are positioned to regulate both the level
      of activity in developing motor circuits and the ascending flow of nociceptive
      information to the brain, thus highlighting a potential role for pacemaker
      activity in the maturation of pain and sensorimotor networks in the central
      nervous system.

PMID- 25380423
TI  - Gilead's interferon-free HCV combo approved.

PMID- 25380422
TI  - $675 million for MRSA antibiotic.

PMID- 25380424
TI  - Novo sets sights on obesity market with diabetes drug.

PMID- 25380425
TI  - Dow's newly approved Enlist fights superweeds.

PMID- 25380427
TI  - Illumina, Thermo Fisher build consortia to develop 'universal' cancer tests.

PMID- 25380426
TI  - J&J buys antiviral firm Alios.

PMID- 25380429
TI  - Anti-IL-5 biologics carve out severe-asthma niche.

PMID- 25380430
TI  - Mouse mAb patent revoked.

PMID- 25380431
TI  - EMA adopts transparency policy.

PMID- 25380432
TI  - Australia upholds BRCA1 gene patent.

PMID- 25380436
TI  - Technology comes to typing.
AB  - As mass spectrometry makes inroads into pathogen identification in the clinical
      laboratory, deep sequencing - even nanopore sequencing - is waiting in the wings.
      Jeffrey L. Fox investigates.

PMID- 25380433
TI  - Big-cap buying bonanza trickles down to small biotech.

PMID- 25380438
TI  - 3D printing for the many, not the few.

PMID- 25380439
TI  - Genetically engineered crops that fly under the US regulatory radar.

PMID- 25380440
TI  - Screening cellular metabolic activity.

PMID- 25380441
TI  - Gregory Stephanopoulos and colleagues reply to Screening cellular metabolic
      activity.

PMID- 25380442
TI  - Antibody claims granted by the European Patent Office.
AB  - A survey of the claims of antibody-related patents granted by the European Patent
      Office and a review of the type and scope of product claims granted for
      antibodies.

PMID- 25380444
TI  - Closing in on pancreatic beta cells.

PMID- 25380445
TI  - Antibacterials for any target.

PMID- 25380446
TI  - Making biology transparent.

PMID- 25380447
TI  - Allosteric targeting of receptor tyrosine kinases.
AB  - The drug discovery landscape has been transformed over the past decade by the
      discovery of allosteric modulators of all major mammalian receptor superfamilies.
      Allosteric ligands are a rich potential source of drugs and drug targets with
      clear therapeutic advantages. G protein-coupled receptors, ligand-gated ion
      channels and intracellular nuclear hormone receptors have all been targeted by
      allosteric modulators. More recently, a receptor tyrosine kinase (RTK) has been
      targeted by an extracellular small-molecule allosteric modulator. Allosteric
      mechanisms of structurally distinct molecules that target the various receptor
      families are more alike than originally anticipated and include selectivity,
      orthosteric probe dependence and pathway-biased signaling. 

PMID- 25380455
TI  - CT features of early type II endoleaks after endovascular repair of abdominal
      aortic aneurysms help predict aneurysm sac enlargement.
AB  - PURPOSE: To determine computed tomographic (CT) features of early type II
      endoleaks associated with aneurysm sac enlargement after endovascular aortic
      aneurysm repair (EVAR) of abdominal aortic aneurysm. MATERIALS AND METHODS:
      Institutional review board approval was not required for this retrospective
      study. The authors reviewed imaging and clinical data from 56 patients (seven
      women, 49 men; mean age +/- standard deviation, 71 years +/- 7.9; age range, 52
      85 years) with early type II endoleak who had undergone EVAR between December
      2002 and December 2011 and who had been followed up with imaging and clinical
      evaluation for at least 6 months. The number and diameter of all feeding and/or
      draining arteries were measured, and endoleaks were classified according to their
      sources into simple inferior mesenteric artery (IMA), simple lumbar artery (LA),
      complex LA, and complex IMA-LA type II endoleaks. Volume and attenuation of the
      nidus were measured. Aneurysm enlargement was defined as an increase in the
      aneurysm volume of more than 5% during follow-up. Simple and multivariate
      logistic regression analyses were performed to identify independent clinical and
      imaging variables associated with aneurysm enlargement. RESULTS: Twenty-three of
      the 56 patients (41%) showed aneurysm sac enlargement during follow-up (mean
      follow-up, 3.0 years +/- 2.0). With the multivariate model, the variables that
      showed the strongest indicators for aneurysm sac enlargement were complex IMA-LA
      type II endoleak (odds ratio [OR] = 10.29, P = .004) and the diameter of the
      largest feeding and/or draining artery (OR = 4.55, P = .013). Patients without
      complex IMA-LA type II endoleak in whom the largest feeding and/or draining
      artery was larger than 3.8 mm and patients with a complex IMA-LA type II endoleak
      in whom the largest feeding and/or draining artery was larger than 2.2 mm were at
      high risk for aneurysm sac enlargement. CONCLUSION: The strongest indicators for
      aneurysm sac enlargement are complex IMA-LA type II endoleak and the diameter of
      the largest feeding and/or draining artery.

PMID- 25380454
TI  - Quality assurance assessment of diagnostic and radiation therapy-simulation CT
      image registration for head and neck radiation therapy: anatomic region of
      interest-based comparison of rigid and deformable algorithms.
AB  - PURPOSE: To develop a quality assurance (QA) workflow by using a robust, curated,
      manually segmented anatomic region-of-interest (ROI) library as a benchmark for
      quantitative assessment of different image registration techniques used for head
      and neck radiation therapy-simulation computed tomography (CT) with diagnostic CT
      coregistration. MATERIALS AND METHODS: Radiation therapy-simulation CT images and
      diagnostic CT images in 20 patients with head and neck squamous cell carcinoma
      treated with curative-intent intensity-modulated radiation therapy between August
      2011 and May 2012 were retrospectively retrieved with institutional review board
      approval. Sixty-eight reference anatomic ROIs with gross tumor and nodal targets
      were then manually contoured on images from each examination. Diagnostic CT
      images were registered with simulation CT images rigidly and by using four
      deformable image registration (DIR) algorithms: atlas based, B-spline, demons,
      and optical flow. The resultant deformed ROIs were compared with manually
      contoured reference ROIs by using similarity coefficient metrics (ie, Dice
      similarity coefficient) and surface distance metrics (ie, 95% maximum Hausdorff
      distance). The nonparametric Steel test with control was used to compare
      different DIR algorithms with rigid image registration (RIR) by using the post
      hoc Wilcoxon signed-rank test for stratified metric comparison. RESULTS: A total
      of 2720 anatomic and 50 tumor and nodal ROIs were delineated. All DIR algorithms
      showed improved performance over RIR for anatomic and target ROI conformance, as
      shown for most comparison metrics (Steel test, P < .008 after Bonferroni
      correction). The performance of different algorithms varied substantially with
      stratification by specific anatomic structures or category and simulation CT
      section thickness. CONCLUSION: Development of a formal ROI-based QA workflow for
      registration assessment demonstrated improved performance with DIR techniques
      over RIR. After QA, DIR implementation should be the standard for head and neck
      diagnostic CT and simulation CT allineation, especially for target delineation.

PMID- 25380456
TI  - Catechol formation: a novel pathway in the metabolism of sterigmatocystin and 11
      methoxysterigmatocystin.
AB  - The mycotoxin sterigmatocystin (STC) has an aflatoxin-like structure including a
      furofuran ring system. Like aflatoxin B1, STC is a liver carcinogen and forms DNA
      adducts after metabolic activation to an epoxide at the furofuran ring. In
      incubations of STC with human P450 isoforms, one monooxygenated and one
      dioxygenated STC metabolite were recently reported, and a GSH adduct was formed
      when GSH was added to the incubations. However, the chemical structures of these
      metabolites were not unambiguously elucidated. We now report that hepatic
      microsomes from humans and rats predominantly form the catechol 9-hydroxy-STC via
      hydroxylation of the aromatic ring. No STC-1,2-oxide and only small amounts of
      STC-1,2-dihydrodiol were detected in microsomal incubations, suggesting that
      epoxidation is a minor pathway compared to catechol formation. Catechol formation
      was also much more pronounced than furofuran epoxidation in the microsomal
      metabolism of 11-methoxysterigmatocystin (MSTC). In support of the preference of
      catechol formation, only trace amounts of the thiol adduct of the 1,2-oxides but
      large amounts of the thiol adducts of the 9-hydroxy-8,9-quinones were obtained
      when N-acetyl-l-cysteine was added to the microsomal incubations of STC and MSTC.
      In addition to hydroxylation at C-9, smaller amounts of 12c-hydroxylated, 9,12c
      dihydroxylated, and 9,11-dihydroxylated metabolites were formed. Our study
      suggests that hydroxylation of the aromatic ring, yielding a catechol, represents
      a major and novel pathway in the oxidative metabolism of STC and MSTC, which may
      contribute to the toxic and genotoxic effects of these mycotoxins.

PMID- 25380457
TI  - Multivariate optimization for extraction of pyrethroids in milk and validation
      for GC-ECD and CG-MS/MS analysis.
AB  - A simple and inexpensive method based on solvent extraction followed by low
      temperature clean-up was applied for determination of seven pyrethroids residues
      in bovine raw milk using gas chromatography coupled to tandem mass spectrometry
      (GC-MS/MS) and gas chromatography with electron-capture detector (GC-ECD). Sample
      extraction procedure was established through the evaluation of seven different
      extraction protocols, evaluated in terms of analyte recovery and cleanup
      efficiency. Sample preparation optimization was based on Doehlert design using
      fifteen runs with three different variables. Response surface methodologies and
      polynomial analysis were used to define the best extraction conditions. Method
      validation was carried out based on SANCO guide parameters and assessed by
      multivariate analysis. Method performance was considered satisfactory since mean
      recoveries were between 87% and 101% for three distinct concentrations. Accuracy
      and precision were lower than +/-20%, and led to no significant differences (p <
      0.05) between results obtained by GC-ECD and GC-MS/MS techniques. The method has
      been applied to routine analysis for determination of pyrethroid residues in
      bovine raw milk in the Brazilian National Residue Control Plan since 2013, in
      which a total of 50 samples were analyzed.

PMID- 25380459
TI  - Expression of mRNA encoding IGF-I, IGF-II, type-I,and II IGF-receptors and IGF
      binding proteins-1-4 during ovarian follicular development in buffalo (Bubalus
      bubalis).
AB  - The present study was designed to investigate the expression pattern of IGF-I,
      IGF-II, type-I and II IGF-receptors, and IGFBP-1-4 in different stages of buffalo
      ovarian preantral follicles (PFs), antral follicles (AFs), ovulatory follicles
      (OFs), and immature (IM) and in vitro matured (MO) oocytes. Buffalo ovaries were
      collected from local abattoir, PFs (200-250 um), AFs (1-3 mm), and OFs (5-8 mm)
      were isolated by mechanical method. PFs, AFs, OFs, and oocytes were lysed to
      release mRNA, reverse transcribed, and then subjected to RT-PCR, whereas protein
      were localized through immunohistochemistry. Relative expression of mRNA
      transcripts was clearly seen for IGF-II, type-I and II IGF-receptors, and IGFBP-1
      4 in all the stages of developing follicles and oocytes. We were unable to detect
      mRNA and protein expression of IGF-1 in any of the oocytes or follicles at any
      stage of the development. IGF-II and both IGF receptors mRNA expression were
      found higher (P < 0.05) in PFs compared to AFs and OFs. Expression of IGFBP-1 and
      2 in PFs, as well as IGFBP-3 and 4 in AFs, was found with higher (P < 0.05)
      levels. The expression results were further confirmed by localization of IGF-II,
      type-I and II IGF-receptors, and IGFBP-1-4 proteins. In conclusion, IGF-II
      appears to be the only ligand that is endogenously expressed by all the
      follicular stages and oocytes, which may act in an autocrine manner through the
      Type-1 IGF receptor. Expression of IGFBP-1-4 and IGF-II suggests the possible
      role of these genes in recruitment, growth, proliferation, and steroidogenic
      responses during developmental phases of buffalo ovarian follicles.

PMID- 25380458
TI  - Intrahippocampal infusion of crotamine isolated from Crotalus durissus terrificus
      alters plasma and brain biochemical parameters.
AB  - Crotamine is one of the main constituents of the venom of the South American
      rattlesnake Crotalus durissus terrificus. Here we sought to investigate the
      inflammatory and toxicological effects induced by the intrahippocampal
      administration of crotamine isolated from Crotalus whole venom. Adult rats
      received an intrahippocampal infusion of crotamine or vehicle and were euthanized
      24 h or 21 days after infusion. Plasma and brain tissue were collected for
      biochemical analysis. Complete blood count, creatinine, urea, glutamic
      oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine
      kinase (CK), creatine kinase-muscle B (CK-MB) and oxidative parameters (assessed
      by DNA damage and micronucleus frequency in leukocytes, lipid peroxidation and
      protein carbonyls in plasma and brain) were quantified. Unpaired and paired t
      tests were used for comparisons between saline and crotamine groups, and within
      groups (24 h vs. 21 days), respectively. After 24 h crotamine infusion promoted
      an increase of urea, GOT, GPT, CK, and platelets values (p <= 0.01), while red
      blood cells, hematocrit and leukocytes values decreased (p <= 0.01).
      Additionally, 21 days after infusion crotamine group showed increased creatinine,
      leukocytes, TBARS (plasma and brain), carbonyl (plasma and brain) and
      micronucleus compared to the saline-group (p <= 0.01). Our findings show that
      crotamine infusion alter hematological parameters and cardiac markers, as well as
      oxidative parameters, not only in the brain, but also in the blood, indicating a
      systemic pro-inflammatory and toxicological activity. A further scientific
      attempt in terms of preserving the beneficial activity over toxicity is required.

PMID- 25380460
TI  - Next generation semiconductor based-sequencing of a nutrigenetics target gene
      (GPR120) and association with growth rate in Italian Large White pigs.
AB  - The GPR120 gene (also known as FFAR4 or O3FAR1) encodes for a functional omega-3
      fatty acid receptor/sensor that mediates potent insulin sensitizing effects by
      repressing macrophage-induced tissue inflammation. For its functional role,
      GPR120 could be considered a potential target gene in animal nutrigenetics. In
      this work we resequenced the porcine GPR120 gene by high throughput Ion Torrent
      semiconductor sequencing of amplified fragments obtained from 8 DNA pools
      derived, on the whole, from 153 pigs of different breeds/populations (two Italian
      Large White pools, Italian Duroc, Italian Landrace, Casertana, Pietrain, Meishan,
      and wild boars). Three single nucleotide polymorphisms (SNPs), two synonymous
      substitutions and one in the putative 3'-untranslated region (g.114765469C > T),
      were identified and their allele frequencies were estimated by sequencing reads
      count. The g.114765469C > T SNP was also genotyped by PCR-RFLP confirming
      estimated frequency in Italian Large White pools. Then, this SNP was analyzed in
      two Italian Large White cohorts using a selective genotyping approach based on
      extreme and divergent pigs for back fat thickness (BFT) estimated breeding value
      (EBV) and average daily gain (ADG) EBV. Significant differences of allele and
      genotype frequencies distribution was observed between the extreme ADG-EBV groups
      (P < 0.001) whereas this marker was not associated with BFT-EBV.

PMID- 25380462
TI  - Influence of DGAT1 K232A polymorphism on milk fat percentage and fatty acid
      profiles in Romanian holstein cattle.
AB  - Milk and dairy products are considered the main sources of saturated fatty acids,
      which are a valuable source of nutrients in the human diet. Fat composition can
      be adjusted through guided nutrition of dairy animals but also through selective
      breeding. Recently, a dinucleotide substitution located in the exon 8 of the gene
      coding for acyl CoA: diacylglycerol acyltransferase 1 (DGAT1), that alters the
      amino acid sequence from a lysine to an alanine (p.Lys232Ala) in the mature
      protein, was shown to have a strong effect on milk fat content in some cattle
      breeds. Therefore, the objectives of this work were to study the occurrence of
      the DGAT1 p.Lys232Ala polymorphism in Romanian Holstein cattle and Romanian
      Buffalo breeds and to further investigate its possible influence on fat
      percentage and fatty acid profiles. The results obtained in this study show that
      in Romanian Holstein cattle the K allele is associated with increased fat
      percentage and higher levels of C16:0 and C18:0 fatty acids. The ratio of
      saturated fatty acids versus unsaturated fatty acids (SFA/UFA) was also higher in
      KK homozygous individuals, whereas the fractions of C14:0, unsaturated C18
      decreased. The DGAT1 p.Lys232Ala polymorphism revealed a high genetic variance
      for fat percentage, unsaturated C18, C16:0, and SFA/UFA. Although the effect of
      this polymorphism was not so evident for short chain fatty acids such as C4:0
      C8:0, it was significant for C14:0 fatty acids. We concluded that selective
      breeding of carriers of the A allele in Romanian Holsteins can contribute to
      improvement in unsaturated fatty acids content of milk. However, in buffalo, the
      lack of the A allele makes selection inapplicable because only the K allele,
      associated with higher saturated fatty acids contents in milk, was identified. 

PMID- 25380461
TI  - Association and expression analysis of single nucleotide polymorphisms of partial
      tumor necrosis factor alpha gene with mastitis in crossbred cattle.
AB  - A total of 129 crossbred cows were selected to explore the genotypic and
      expression profiling of partial TNF-alpha gene and its association with mastitis
      susceptibility. Two exon spanning region of TNF-alpha gene (221 bp and 239 bp)
      were amplified by Polymerase Chain Reaction (PCR). The different genotypic
      analysis by SSCP revealed that 221 bp fragment was monomorphic, whereas 239 bp
      was polymorphic. Association studies revealed that AA genotypes of 239 bp were
      more prevalent in mastitis group and the mRNA expression of TNF-alpha was
      significantly (P < 0.05) higher in AA genotypic animals compare to AB and BB.
      This suggested that genotypes AB and BB may be used as candidate markers for
      mastitis resistance selection in dairy cattle. 

PMID- 25380463
TI  - In-vitro characterization and evaluation of apoptotic potential of bicistronic
      plasmid encoding HN gene of Newcastle disease virus and human TNF-alpha.
AB  - The viral gene oncotherapy in combination with cytokines emerges as an exciting
      strategy for cancer therapy due to its minimal side effects and tumor
      specificity. HN is the surface protein of NDV which is involved in virus
      infectivity and is known to kill many cancerous cell types. TNF-alpha, a
      multifactorial cytokine has direct anti-tumor activity by activating the
      extrinsic pathways of apoptosis. In the present study, HN gene of NDV and TNF
      alpha of human were cloned at multiple cloning sites (MCS) 1 and 2 of bicistronic
      expression vector pVIVO2. Expression pattern of recombinant clone was checked on
      transcriptional and translational level by RT-PCR, Immunofluorescence assay and
      flow cytometry. On flow cytometric analysis HN gene expression was found to be
      28.30 +/- 1.21; 5.22 +/- 0.60%, and TNF-alpha gene expression was found to be
      15.44 +/- 0.42; 6.51 +/- 0.757%, in HeLa cells transfected with
      pVIVO.nd.hn.hu.tnf and pVIVO2 empty vector control, respectively. These assays
      confirm that HN and TNF-alpha act synergistically in the induction of apoptosis
      in HeLa cells. 

PMID- 25380465
TI  - Differential Toll-like receptor (TLR) mRNA expression patterns during chicken
      embryological development.
AB  - Toll-like receptors (TLRs), important components of innate immune response, play
      a pivotal role in early recognition of pathogen as well as in the initiation of
      robust and specific adaptive immune response. In the present study, the
      expression profile of chicken TLRs (TLR2A, TLR3, TLR4, TLR5, TLR7, TLR15, and
      TLR21) in various chicken embryonic tissues during embryo development was
      examined by real-time PCR assay. All the TLR mRNAs were expressed in whole
      embryonic tissue as early as 3rd embryonic day (ED). Four of the seven TLRs
      (TLR2, TLR3, TLR4, and TLR7) mRNA expressions were significantly (P < 0.01)
      higher at 12ED relative to expression at 3 ED, whereas TLR15 mRNA expression was
      significantly (P < 0.01) higher on 7ED and TLR5 and 21 were highly expressed on
      18 ED. Among all the TLRs investigated TLR4 mRNA was the highest expressed and
      TLR15 mRNA expression was the lowest in all tissues during chicken embryo
      development. Tissue wise analysis of mRNA expression of TLRs showed that liver
      expressed significantly (P < 0.01) higher levels of most of the genes (TLR2,
      TLR4, and TLR21). However no significant difference was found in TLR15 mRNA
      expression among the tissues during development. Our results suggest the innate
      preparedness of chicken embryos and also a possible role for TLRs in the
      regulation of chicken embryo development that needs to be further evaluated. 

PMID- 25380464
TI  - Molecular cloning, sequence, and phylogenetic analysis of T helper 1 cytokines of
      Pashmina goats.
AB  - Cytokines play an important role in regulation of immune responses either in
      health or disease. In the present study, the cDNAs encoding mature Interleukin
      (IL)-2, interferon gamma (IFN-gamma), and IL-12 p35 and p40 of Pashmina goat were
      cloned and sequenced. The amino acid sequence was deduced from nucleotide
      sequence and compared with those available in GeneBank. Mature forms of goat IL
      2, IFN-gamma, IL-12 p35, and IL-12 p40 composed of 135, 143, 196, and 305 amino
      acid residues, respectively. Comparison of amino acid sequence of goat IL-2 with
      sheep, buffalo, cattle, pig, camel, cat, and human sequences showed homology
      percentages of 100, 97.8, 96.3, 72.4, 72.4, 67.2, and 64.7, respectively. Amino
      acid sequence of goat IFN-gamma showed 98.6, 95.8, 81.1, 81.8, 80.4, and 62.9
      percent homology with sheep, bovine, pig, horse, dog, and humans, respectively.
      Homology ranging from 81.6 to 99% for IL-12 p35 sequences and 85.6 to 100% for IL
      12 p40 sequences at amino acid level were observed across these species. Multiple
      sequence alignment and phylogenetic analysis of goat cytokines revealed close
      relationship with sheep sequence. 

PMID- 25380467
TI  - Association of IL8 -105G/A with mastitis somatic cell score in Chinese Holstein
      dairy cows.
AB  - The single nucleotide polymorphisms (SNPs) in the 5' upstream of bovine IL8 gene
      were investigated in 810 Chinese Holstein cows from 35 bull families in a dairy
      farm in Shanghai using polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) technique. The Real-time PCR and Western blot were used
      to detect the mRNA and protein levels of genotype Chinese Holstein dairy cows.
      The results showed that one SNP -105G>A was detected, designating three genotypes
      (GG, GA and AA) with respective frequencies of 0.38, 0.46, and 0.16. The
      significant association of the SNP -105G>A with somatic cell score (SCS) was
      identified. Genotype GG had a significantly lower SCS than genotype GA or AA (P <
      0.01), and the relative mRNA expression and protein level of GG was found to be
      the highest. These results suggest that the genotype GG may be a useful genetic
      marker for mastitis resistance selection and breeding in Chinese Holstein dairy
      cows.

PMID- 25380466
TI  - MAC-T cells as a tool to evaluate lentiviral vector construction targeting
      recombinant protein expression in milk.
AB  - Prior to generating transgenic animals for bioreactors, it is important to
      evaluate the vector constructed to avoid poor protein expression. Mammary
      epithelial cells cultured in vitro have been proposed as a model to reproduce the
      biology of the mammary gland. In the present work, three lentiviral vectors were
      constructed for the human growth hormone (GH), interleukin 2 (IL2), and
      granulocyte colony-stimulating factor 3 (CSF3) genes driven by the bovine beta
      casein promoter. The lentiviruses were used to transduce mammary epithelial cells
      (MAC-T), and the transformed cells were cultured on polystyrene in culture medium
      with and without prolactin. The gene expression of transgenes was evaluated by
      PCR using cDNA, and recombinant protein expression was evaluated by Western
      blotting using concentrated medium and cellular extracts. The gene expression, of
      the three introduced genes, was detected in both induced and non induced MAC-T
      cells. The human GH protein was detected in the concentrated medium, whereas CSF3
      was detected in the cellular extract. Apparently, the cellular extract is more
      appropriate than the concentrated medium to detect recombinant protein,
      principally because concentrated medium has a high concentration of bovine serum
      albumin. The results suggest that MAC-T cells may be a good system to evaluate
      vector construction targeting recombinant protein expression in milk. 

PMID- 25380468
TI  - Assessment of genetic variability and structuring of riverine buffalo population
      (Bubalus bubalis) of Indo-Gangetic basin.
AB  - The buffalo population of Uttar Pradesh (UP) constitutes 26.1% of the total
      buffalo population of India, yet this population has not been classified into
      distinct breeds or subpopulations due to lack of systematic study. Genetic
      variation at 30 microsatellite loci was examined and statistical analysis was
      carried out to reveal genetic diversity, demographic parameters of these
      buffaloes and to investigate the existence of population substructures underlying
      geographical distribution. The mean number of alleles per locus was 13.26 and
      mean effective number of alleles was 3.74, whereas mean observed and expected
      heterozygosities were found to be 0.57 and 0.67 in UP buffaloes. Principal
      component analysis (PCA) based on allele frequency data revealed subclustering of
      UP buffalo population. Bayesian analysis result also revealed clear membership of
      individuals into five clusters indicating a genetic subdivision within the UP
      buffalo population. The buffaloes of Western and Central regions of UP were
      subtly separated while buffaloes of Tarai area and Bhadawari buffaloes revealed
      distinctive population structure. The buffaloes of Mau, Ballia and Ghazipur
      districts of Eastern region also had a distinctive genetic structure. The
      analysis of data on buffaloes of Indo-Gangetic plains revealed that population
      was in mutation drift equilibrium. The observed mean M ratio in the population
      was above the critical significance value (Mc) suggesting that it has not
      suffered any severe reduction in effective population size. The statistical tests
      revealed a historical constancy of size of buffalo in this geographical area. The
      high level of genetic variability indicates UP buffalo population is a vast
      reservoir of genetic diversity and this shall help in taking informed
      conservation decisions and sustainable utilization. 

PMID- 25380469
TI  - Novel polymorphisms in porcine 3'UTR of the leptin gene, including a rare variant
      within target sequence for MIR-9 gene in Duroc breed, not associated with
      production traits.
AB  - The leptin gene (LEP) is considered as a functional candidate for production
      traits in livestock due to its crucial role in energy homeostasis. Because
      polymorphisms in regulatory sequences may affect gene expression, we searched for
      them in the 3'UTR of LEP and analyzed their association with production traits.
      Four breeds and a composite line were studied. In the Polish Landrace and Polish
      Large White breeds, 8 SNPs and 1 indel were observed; whereas, in the Duroc
      breed, 9 specific SNPs were found. Pietrain and Line 990 were monomorphic. One
      SNP (g.+168C>T), observed in the Duroc breed only, was located within a target
      site for microRNA (miR-9). Association studies showed a weak association between
      one SNP (c.+846C>T) and abdominal fat weight in the Polish Landrace only. Thus,
      we concluded that contribution of polymorphisms in the 3'UTR to phenotypic
      variability of pig production traits is marginal. Moreover, we presented an
      overview of known polymorphisms (128) in the pig leptin gene. 

PMID- 25380471
TI  - Reactive Oxygen Species, Mitochondria, and Endothelial Cell Death during In Vitro
      Simulated Dives.
AB  - PURPOSE: Excessive reactive oxygen species (ROS) is considered a consequence of
      hyperoxia and a major contributor to diving-derived vascular endothelial damage
      and decompression sickness. The aims of this work were: 1) to directly observe
      endothelial ROS production during simulated air dives as well as its relation
      with both mitochondrial activity and cell survival; and 2) to determine which
      ambient factor during air diving (hydrostatic pressure or oxygen and/or nitrogen
      partial pressure) is responsible for the observed modifications. METHODS: In
      vitro diving simulation was performed with bovine arterial endothelial cells
      under real-time observation. The effects of air diving, hydrostatic, oxygen and
      nitrogen pressures, and N-acetylcysteine (NAC) treatment on mitochondrial ROS
      generation, mitochondrial membrane potential and cellular survival during
      simulation were investigated. RESULTS: Vascular endothelial cells performing air
      diving simulation suffered excessive mitochondrial ROS, mitochondrial
      depolarization, and cell death. These effects were prevented by NAC: after NAC
      treatment, the cells presented no difference in damage from nondiving cells.
      Oxygen diving showed a higher effect on ROS generation but lower impacts on
      mitochondrial depolarization and cell death than hydrostatic or nitrogen diving.
      Nitrogen diving had no effect on the inductions of ROS, mito-depolarization, or
      cell death. CONCLUSION: This study is the first direct observation of
      mitochondrial ROS production, mitochondrial membrane potential and cell survival
      during diving. Simulated air SCUBA diving induces excessive ROS production, which
      leads to mitochondrial depolarization and endothelial cell death. Oxygen partial
      pressure plays a crucial role in the production of ROS. Deleterious effects of
      hyperoxia-induced ROS are potentiated by hydrostatic pressure. These findings
      hold new implications for the pathogenesis of diving-derived endothelial
      dysfunction.

PMID- 25380470
TI  - Multi-residue method for determination of 238 pesticides in Chinese cabbage and
      cucumber by liquid chromatography-tandem mass spectrometry: comparison of
      different purification procedures.
AB  - This paper describes the comparison of five sample cleanup procedures for the
      determination of 238 pesticides via triple quadrupole liquid chromatography
      tandem mass spectrometry (LC-MS/MS, with only 10 min of chromatographic running
      time) in Chinese cabbage and cucumber. Samples were extracted with a quick, easy,
      cheap, effective, rugged, and safe (QuECHERS) preparation method and cleanup with
      different sorbents, including primary secondary amine (PSA), multi-walled carbon
      nanotubes (MWCNTs), and polystyrene (PLS), to find out the most suitable cleanup
      methods for Chinese cabbage and cucumber. The recovery and matrix effect were
      evaluated by monitoring the main parameters in one group of 238 pesticides at the
      spiked level of 8 and 40 MUg/kg. In Chinese cabbage, when PSA dispersive solid
      phase extraction (D-SPE) was applied, recoveries of 183 pesticides ranged between
      70 and 120% with relative standard deviation (RSD) values lower than 20% at a
      spiked level of 40 MUg/kg, indicating the effectiveness of the purification step.
      In cucumber, 203 pesticides were in the 70-120% recovery range with good
      reproducibility by PSA mini-cartridge column cleanup at a spiked level of 40
      MUg/kg and RSD values were generally below 20%. The limits of quantitation [LOQs;
      signal-to-noise (S/N) = 10] were in the range of 0.16-10.20 MUg/kg for Chinese
      cabbage and 0.06-21.06 MUg/kg for cucumber, while the limits of detection (LODs;
      S/N = 3) were between 0.05 and 3.06 MUg/kg and between 0.02 and 6.32 MUg/kg in
      Chinese cabbage and cucumber, respectively. The proposed methods that might be
      applied for the multi-residue analysis in Chinese cabbage and cucumber are
      contributed to their rapid speed and good recoveries. 

PMID- 25380472
TI  - Exercise Intensity and Duration Effects on In Vivo Immunity.
AB  - PURPOSE: To examine the effects of intensity and duration of exercise stress on
      induction of in vivo immunity in humans using experimental contact
      hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP).
      METHODS: Sixty-four healthy males completed either 30 min running at 60% VO2peak
      (30MI), 30 min running at 80% VO2peak (30HI), 120 min running at 60% VO2peak
      (120MI), or seated rest (CON). Twenty min later, the subjects received a
      sensitizing dose of DPCP; and 4 wk later, the strength of immune reactivity was
      quantified by measuring the cutaneous responses to a low dose-series challenge
      with DPCP on the upper inner arm. Circulating epinephrine, norepinephrine and
      cortisol were measured before, after, and 1 h after exercise or CON. Next, to
      understand better whether the decrease in CHS response on 120MI was due to local
      inflammatory or T-cell-mediated processes, in a crossover design, 11 healthy
      males performed 120MI and CON, and cutaneous responses to a dose series of the
      irritant, croton oil (CO), were assessed on the upper inner arm. RESULTS: Immune
      induction by DPCP was impaired by 120MI (skinfold thickness -67% vs CON; P <
      0.05). However, immune induction was unaffected by 30MI and 30HI despite elevated
      circulating catecholamines (30HI vs pre: P < 0.01) and greater circulating
      cortisol post 30HI (vs CON; P < 0.01). There was no effect of 120MI on skin
      irritant responses to CO. CONCLUSIONS: Prolonged moderate-intensity exercise, but
      not short-lasting high- or short-lasting moderate-intensity exercise, decreases
      the induction of in vivo immunity. No effect of prolonged moderate-intensity
      exercise on the skin's response to irritant challenge points toward a suppression
      of cell-mediated immunity in the observed decrease in CHS. Diphenylcyclopropenone
      provides an attractive tool to assess the effect of exercise on in vivo immunity.

PMID- 25380473
TI  - Decreased Prevalence of Exercise Expiratory Flow Limitation from Pre- to
      Postpuberty.
AB  - PURPOSE: We recently reported a high prevalence of expiratory flow limitation
      (EFL) independent of sex in prepubescent children that exceeds the prevalence
      reported in adults. It is unknown how transpubertal maturation and growth affect
      pulmonary function, specifically EFL, during exercise. The purpose of this
      longitudinal study was to investigate the changes in EFL, including sex
      differences, from pre- to postpuberty. METHODS: Twenty-one children (age 12-16
      yr, 11 boys and 10 girls) were recruited from 40 prepubescent children who
      completed testing in our laboratory ~5 yr ago. Subjects completed pulmonary
      function tests before and after an incremental exercise test to exhaustion on a
      cycle ergometer. EFL was determined using the percent tidal volume overlap
      method. RESULTS: Nineteen of 21 subjects (10 boys and 9 girls, ~90%) exhibited
      EFL prepuberty, whereas only 7 of 21 subjects (5 boys and 2 girls, 33%) exhibited
      EFL postpuberty. Boys had a significantly greater forced vital capacity (FVC)
      than girls both pre- (~15%) and postpuberty (boys: 4.73 +/- 0.53 L; girls: 3.80
      +/- 0.29 L). Maximal aerobic capacity (VO2max) significantly increased (boys:
      ~120%; girls: ~110%) from pre- to postpuberty and was greater (P < 0.05) in boys
      postpuberty (boys: 2.76 +/- 0.43 L.min; girls: 1.94 +/- 0.35 L.min). VE/VCO2
      significantly decreased (~13%) in boys and girls during maximal exercise.
      Postpuberty, subjects regulated tidal breathing at significantly higher lung
      volumes (greater expiratory reserve volume/FVC and lower inspiratory reserve
      volume/FVC) during exercise compared with prepuberty. CONCLUSION: Our findings
      suggest that the prevalence of EFL declines as children mature from pre- to
      postpuberty, likely because of increases in lung size, decreases in VE/VCO2,
      and/or changes in breathing mechanics that are greater than increases in maximal
      ventilation that occur with increased pulmonary gas exchange.

PMID- 25380474
TI  - Accelerometer Validation of Questionnaires Used in Clinical Settings to Assess
      MVPA.
AB  - INTRODUCTION: The exercise vital sign (EVS) and General Practice Physical
      Activity Questionnaire (GPPAQ) are questionnaires designed for clinical settings
      to identify individuals who are not meeting physical activity (PA) guidelines in
      the United States and United Kingdom, respectively. To date, neither has been
      objectively validated. METHODS: Subjects (N = 76) from the United States (n = 38;
      age, 49 +/- 20 yr) and United Kingdom (n = 38; age, 43 +/- 21 yr) completed a
      health history questionnaire, wore an accelerometer for 7 d, and then completed
      the EVS and GPPAQ. Accelerometry, EVS, and GPPAQ data were scored to dichotomize
      subjects into groups of meeting (>=150 min of moderate-to-vigorous PA (MVPA) per
      week) or not meeting (<150 min of MVPA per week) the PA guidelines, and
      accelerometry was used as a criterion measure for comparing both questionnaires.
      The sensitivity and specificity of the EVS and GPPAQ were calculated to represent
      the ability of the questionnaires to identify subjects who did not and did meet
      the PA guidelines. Total MVPA accumulated in >=10-min bouts were compared between
      accelerometry and the EVS using a 2 * 2 * 2 repeated measures ANOVA with one
      within-subjects effect (PA assessment method) and two between-subjects effects
      (gender and country). The alpha level was P = 0.05 for all analyses. RESULTS: The
      EVS had marginally better sensitivity (59% vs 46%) and specificity (77% vs 50%)
      than the GPPAQ. The EVS grossly overestimated the minutes of MVPA when compared
      to accelerometry (P < 0.05) for all subjects, except UK women. CONCLUSION: In
      practice, the EVS and GPPAQ may not identify ~50% of patients who should be
      advised to increase their PA. Therefore, physicians should advocate that all of
      their patients adopt an active lifestyle, including the achievement of >=150 min
      of MVPA per week.

PMID- 25380475
TI  - Soft Tissue Deformations Contribute to the Mechanics of Walking in Obese Adults.
AB  - Obesity not only adds to the mass that must be carried during walking but also
      changes body composition. Although extra mass causes roughly proportional
      increases in musculoskeletal loading, less well understood is the effect of
      relatively soft and mechanically compliant adipose tissue. PURPOSE: This purpose
      of this study was to estimate the work performed by soft tissue deformations
      during walking. The soft tissue would be expected to experience damped
      oscillations, particularly from high force transients after heel strike, and
      could potentially change the mechanical work demands for walking. METHODS: We
      analyzed treadmill walking data at 1.25 m.s for 11 obese (BMI >30 kg.m) and nine
      nonobese (BMI <30 kg.m) adults. The soft tissue work was quantified with a method
      that compares the work performed by lower extremity joints as derived using
      assumptions of rigid body segments, with that estimated without rigid body
      assumptions. RESULTS: Relative to body mass, obese and nonobese individuals
      perform similar amounts of mechanical work. However, negative work performed by
      soft tissues was significantly greater in obese individuals (P = 0.0102),
      equivalent to approximately 0.36 J.kg vs 0.27 J.kg in nonobese individuals. The
      negative (dissipative) work by soft tissues occurred mainly after heel strike
      and, for obese individuals, was comparable in magnitude to the total negative
      work from all of the joints combined (0.34 J.kg vs 0.33 J.kg for obese and
      nonobese adults, respectively). Although the joints performed a relatively
      similar amount of work overall, obese individuals performed less negative work
      actively at the knee. CONCLUSIONS: The greater proportion of soft tissues in
      obese individuals results in substantial changes in the amount, location, and
      timing of work and may also affect metabolic energy expenditure during walking.

PMID- 25380476
TI  - Neuromuscular Strategies during Cycling at Different Muscular Demands.
AB  - PURPOSE: This study investigated muscle coordination while pedaling at 150 and
      300 W with a cadence of 90 rpm. Changes in the variability of the
      electromyographic (EMG) signals were quantified in 14 subjects. METHODS:
      Principal component analysis was used to find correlated EMG patterns among seven
      leg muscles that reflect neuromuscular strategies while pedaling. Sample entropy
      was used to assess the regularity of the short-term fluctuations of the EMG.
      Signal structure relates to the autocorrelation and to the information in the
      phase of the signal. This study used the information encrypted in the phase to
      quantify neuromuscular control and compared the results to phase-randomized
      surrogate data. RESULTS: Although the pattern remained similar, the correlation
      between individual muscles showed effort-dependent differences. Increased
      workload altered the overall neuromuscular strategy indicated by changes in the
      contribution of individual muscles to the movement. Additionally, the executed
      strategy was characterized by increased structure. Regularity of the short-term
      fluctuations in the EMG increased significantly with effort level. Both
      experimental conditions showed more structure in the phase of the EMG compared to
      the surrogate data. CONCLUSIONS: This increased structure in the EMG signal may
      represent a less random and more orderly recruited firing pattern during the
      pedaling task at higher effort levels.

PMID- 25380477
TI  - Perceived Sources of Team Confidence in Soccer and Basketball.
AB  - PURPOSE: Although it is generally accepted that team confidence is beneficial for
      optimal team functioning and performance, little is known about the predictors of
      team confidence. The present study was aimed to shed light on the precursors of
      both high and low team confidence in two different sports. A distinction is made
      between sources of process-oriented team confidence (i.e., collective efficacy)
      and sources of outcome-oriented team confidence (i.e., team outcome confidence),
      which have often been confounded in previous research. METHODS: In a first step,
      two qualitative studies were conducted to identify all possible sources of team
      confidence in basketball and in soccer. In a second step, three quantitative
      studies were conducted to further investigate the sources of team outcome
      confidence in soccer (N = 1028) and in basketball (N = 867), and the sources of
      collective efficacy in basketball (N = 825). RESULTS: Players perceived high
      quality performance as the most important factor for their team outcome
      confidence. With regard to collective efficacy, team enthusiasm was perceived as
      most predictive determinant. Positive coaching emerged as second most decisive
      factor for both types of team confidence. In contrast, negative communication and
      expression by the players or the coach was perceived as the most decisive
      predictor of low levels of team confidence. At item level, all studies pointed to
      the importance of team confidence expression by the athlete leaders (i.e., leader
      figures within the team) and the coach. CONCLUSION: The present manuscript sheds
      light on the precursors of high and low levels of team confidence. Athlete
      leaders and the coach emerged as key triggers of both upward and downward spirals
      of team confidence, thereby contaminating all team members.

PMID- 25380478
TI  - Targeting Abdominal Adiposity and Cardiorespiratory Fitness in the Workplace.
AB  - PURPOSE: The prevalence of numerous chronic metabolic diseases is increasing
      worldwide with considerable personal and societal consequences. The aim of our
      study was to test the hypothesis that assessment of waist circumference (WC) and
      of cardiorespiratory fitness (CRF) could be relevant clinical targets of a simple
      preventive approach designed to improve cardiometabolic risk (CMR) profile at the
      workplace. METHODS: A total of 787 employees participated in a pilot project of
      the "Grand Defi Entreprise." This challenge involved a 3-month in-house
      competition to favor peer support in the adoption of healthier lifestyle habits.
      For that purpose, the participating companies offered a comprehensive
      cardiometabolic/cardiorespiratory health assessment performed at the workplace
      with a mobile risk assessment unit before and after the contest
      (nutrition/physical activity (PA) questionnaires, resting blood pressure (BP),
      anthropometric measurements, lipid profile, and submaximal treadmill test).
      RESULTS: At baseline, more than 43% of workers were considered sedentary or
      moderately inactive (<3.5 h.wk of physical activity). Furthermore, the proportion
      of subjects in the high-risk category of nutritional quality index (NQI) was high
      (49%). After 3 mo, NQI and PA level improved. Reductions in WC (-4.2 +/- 4.0 cm,
      P < 0.0001), in heart rate at a standardized submaximal workload (-4 +/- 10 bpm,
      P < 0.0001) as well as in resting systolic (-6 +/- 11 mm Hg) and diastolic (-4 +/
      7 mm Hg) blood pressure were also observed. Improvements in WC and CRF were
      associated with improvements in the CMR profile. CONCLUSION: Results of this
      study show the added value of measuring/targeting WC and CRF as a relevant
      approach to reduce CMR at the workplace. Results also suggest that putting in
      place a permissive "in-house ecosystem" within the company is relevant to promote
      the adoption of healthier lifestyle habits.

PMID- 25380479
TI  - VO(2max) and Microgravity Exposure: Convective versus Diffusive O(2) Transport.
AB  - Exposure to a microgravity environment decreases the maximal rate of O2 uptake
      (VO(2max)) in healthy individuals returning to a gravitational environment. The
      magnitude of this decrease in VO(2max) is, in part, dependent on the duration of
      microgravity exposure, such that long exposure may result in up to a 38% decrease
      in VO(2max). This review identifies the components within the O(2) transport
      pathway that determine the decrease in postmicrogravity VO(2max) and highlights
      the potential contributing physiological mechanisms. A retrospective analysis
      revealed that the decline in VO(2max) is initially mediated by a decrease in
      convective and diffusive O(2) transport that occurs as the duration of
      microgravity exposure is extended. Mechanistically, the attenuation of O(2)
      transport is the combined result of a deconditioning across multiple organ
      systems including decreases in total blood volume, red blood cell mass, cardiac
      function and mass, vascular function, skeletal muscle mass, and, potentially,
      capillary hemodynamics, which become evident during exercise upon re-exposure to
      the head-to-foot gravitational forces of upright posture on Earth. In summary,
      VO(2max) is determined by the integration of central and peripheral O(2)
      transport mechanisms, which, if not maintained during microgravity, will have a
      substantial long-term detrimental impact on space mission performance and
      astronaut health.

PMID- 25380480
TI  - Unveiling the inner workings of live bacteria using super-resolution microscopy.

PMID- 25380482
TI  - Strong vortical flows generated by the collective motion of magnetic particle
      chains rotating in a fluid cell.
AB  - Magnetic microparticles, assembled into chains that are actuated with rotating
      magnetic fields, can be used as microstirrers to promote fluid transport and
      biochemical reactions in microfluidic systems. We show that, within a certain
      range of magnetic field rotation frequency, the microstirrers exhibit a coherent
      collective motion: the rotating magnetic particle chains move throughout the
      volume of a flat fluid cell and generate very strong (~1 mm s(-1)) and global (9
      mm) vortical fluid flows, with many eddy-type substructures that fluctuate
      continuously in time, resembling turbulent flow. The collective motion makes the
      microstirrers not only defy gravity, but also move against magnetic field
      gradients. The induced fluid flow is directly related to the stirring rate and
      the amount of magnetic particle chains. The observed behavior is caused by the
      magnetic and hydrodynamic interactions between the magnetic microparticles and
      the fluid. We utilized the phenomenon of swarming particles to enhance
      biochemical assays with magnetic capture particles (4000 MUL(-1)) and IgG targets
      (500 pM). When compared to a reference system of sedimented magnetic capture
      particles, magnetic actuation leads to both a ~9 times increase in the initial
      assay kinetics as well as a ~7 times increase of target capture signal after 30
      minutes. 

PMID- 25380481
TI  - Identification of master genes involved in liver key functions through
      transcriptomics and epigenomics of methyl donor deficiency in rat: relevance to
      nonalcoholic liver disease.
AB  - SCOPE: Our study aims to investigate molecular events associated to methyl donor
      deficiency (MDD) by analyzing the transcriptome and the methylome of MDD rats in
      liver. METHODS AND RESULTS: Twenty-one-day-old rats born to mothers fed either
      with a standard diet or a MDD diet during gestation and lactation were compared.
      From a total of 44 000 probes for 26 456 genes, we found two gene clusters in MDD
      rats whose expression levels had significant differences compared with controls:
      3269 overexpressed (p < 0.0009) and 2841 underexpressed (p < 0.0004) genes.
      Modifications of DNA methylation were found in the promoter regions of 1032 genes
      out of 14 981 genes. Ontological analyses revealed that these genes are mainly
      involved in glucose and lipid metabolism, nervous system, coagulation, ER stress,
      and mitochondrial function. CONCLUSION: Putative master genes exhibiting changes
      in both gene expression and DNA methylation are limited to 266 genes and are
      mainly involved in the renin-angiotensin system (n = 3), mitochondrion metabolism
      (n = 18), and phospholipid homeostasis (n = 3). Most of these master genes
      participate in nonalcoholic fatty liver disease. The adverse effects of MDD on
      the metabolic process indicate the beneficial impact of folate and vitamin B12,
      especially during the perinatal period.

PMID- 25380483
TI  - Effects of tadalafil-Type-V phosphodiesterase enzyme inhibitor-On rats with
      spinal trauma.
AB  - In this research, the effect of tadalafil, a selective inhibitor of cyclic
      guanosine monophosphate-specific phosphodiesterase type 5, on rats with spinal
      trauma was evaluated. The evaluation consisted of neurological examination and
      biochemical parameters. Twenty healthy male Wistar albino rats were used in this
      study. They were separated into three groups: tadalafil-receiving (TD) group
      (n=7), laminectomy and trauma (LT) group (n=7), and just laminectomy group (n=6).
      The TD group received daily dose of tadalafil (10 mg/kg) for a week along with
      bait and water. Each rat's spinal cord was dissected with utter caution. The
      spinal cord was traumatized by Allen's weight-drop method. Using a standard
      apparatus, 5 g of weight was dropped from a height of 10 cm on the spinal cords
      of the TD and LT (laminectomy+trauma) group. No extra maneuvers were conducted on
      the laminectomy group. A day later, the rat's functional neurological status was
      examined followed by re-exploration of the spinal cord for sampling 1 cm of
      tissue. The Tarlov scale was used to evaluate the functional neurological status.
      The modified Tarlov scale was rated to be significantly higher in the TD group
      than that in the LT group. For the biochemical parameters, malondialdehyde (MDA)
      and cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha) involved in the inflammatory process were examined. MDA--an indicator of
      lipid peroxidation--was found to be significantly lower in the TD group compared
      with that in the LT group. TNF-alpha and IL-6 levels were also found to be lower
      in the TD group compared with those in the LT group. Shortly, this research
      showed that the use of TD group in spinal trauma resulted in better neurological
      outcome and significant improvement in biochemical parameters.

PMID- 25380484
TI  - Transforming growth factor-beta-induced long noncoding RNA promotes liver cancer
      metastasis via RNA-RNA crosstalk.

PMID- 25380485
TI  - Evaluation of Retinal Nerve Fiber Layer Thickness in Acromegalic Patients Using
      Spectral-Domain Optical Coherence Tomography.
AB  - PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness in acromegalic
      patients. METHODS: A study group of 29 patients with acromegaly and a control
      group of 38 age-matched healthy individuals were enrolled in a cross-sectional
      study. The study group was further divided by tumor size into two subgroups, a
      macroadenoma group and a microadenoma group. Serum growth hormone (GH) and
      insulin-like growth factor-1 (IGF-I) levels were detected at the time of
      ophthalmological examination in the study group. In both the study and control
      group, the RNFL thickness in the four quadrants was measured by optical coherence
      tomography. The relationship between GH and IGF-I levels and RNLF thickness was
      also evaluated. RESULTS: The difference in mean RNLF thickness in all quadrants
      between the study and control groups was not statistically significant. In
      acromegalic patients with macroadenoma, the mean RNLF thickness of the inferior
      quadrant decreased significantly compared to both patients with microadenoma and
      healthy individuals (p = 0,032 and p = 0,046). GH and IGF-1 levels were not
      significantly correlated with the RNLF thickness in the study group. CONCLUSIONS:
      Excessive GH and IGF-1 levels do not affect the optic nerve or RNLF thickness,
      whereas the RNLF becomes thinner in the inferior quadrant in acromegalic patients
      with macroadenoma as a result of the chiasmal compression.

PMID- 25380487
TI  - Tunable optical properties of hybrid inorganic-organic [(TiO2)m(Ti-O-C6H4-O-)k]n
      superlattice thin films.
AB  - A combined atomic layer deposition (ALD) and molecular layer deposition (MLD)
      process was developed to fabricate inorganic-organic [(TiO2)m(Ti-O-C6H4-O-)k]n
      thin films from TiCl4, water and hydroquinone (HQ) precursors, and in particular,
      superlattice structures where single-molecular organic layers (k = 1) are
      periodically sandwiched between thicker TiO2 layers (m > 1). The incorporation of
      organic layers was found to systematically blue-shift the optical band gap of
      TiO2 with decreasing superlattice period and--most importantly--to sensitize the
      TiO2 layers to visible light over a considerable part of the visible range below
      700 nm, a fact that could be of substantial interest for photocatalysis and solar
      cell applications.

PMID- 25380488
TI  - Preparation of double emulsions using hybrid polymer/silica particles: new
      pickering emulsifiers with adjustable surface wettability.
AB  - A facile route for the preparation of water-in-oil-in-water (w/o/w) double
      emulsions is described for three model oils, namely, n-dodecane, isopropyl
      myristate, and isononyl isononanoate, using fumed silica particles coated with
      poly(ethylene imine) (PEI). The surface wettability of such hybrid PEI/silica
      particles can be systematically adjusted by (i) increasing the adsorbed amount of
      PEI and (ii) addition of 1-undecanal to the oil phase prior to homogenization. In
      the absence of this long-chain aldehyde, PEI/silica hybrid particles (PEI/silica
      mass ratio = 0.50) produce o/w Pickering emulsions in all cases. In the presence
      of 1-undecanal, this reagent reacts with the primary and secondary amine groups
      on the PEI chains via Schiff base chemistry, which can render the PEI/silica
      hybrid particles sufficiently hydrophobic to stabilize w/o Pickering emulsions at
      20  degrees C. Gas chromatography, (1)H NMR and X-ray photoelectron spectroscopy
      provide compelling experimental evidence for this in situ surface reaction, while
      a significant increase in the water contact angle indicates markedly greater
      hydrophobic character for the PEI/silica hybrid particles. However, when
      PEI/silica hybrid particles are prepared using a relatively low adsorbed amount
      of PEI (PEI/silica mass ratio = 0.075) only o/w Pickering emulsions are obtained,
      since the extent of surface modification achieved using this Schiff base
      chemistry is insufficient. Fluorescence microscopy and laser diffraction studies
      confirm that highly stable w/o/w double emulsions can be achieved for all three
      model oils. This is achieved by first homogenizing the relatively hydrophobic
      PEI/silica hybrid particles (PEI/silica mass ratio = 0.50) with an oil containing
      3% 1-undecanal to form an initial w/o emulsion, followed by further
      homogenization using an aqueous dispersion of relatively hydrophilic PEI/silica
      particles (PEI/silica mass ratio = 0.075). Dye release from the internal aqueous
      cores into the aqueous continuous phase was monitored by visible absorption
      spectroscopy. These studies indicate immediate loss of 12-18% dye during the high
      speed homogenization that is required for double emulsion formation, but no
      further dye release is observed at 20  degrees C for at least 15 days thereafter.

PMID- 25380486
TI  - Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing
      breast cancer survival, stemness and pro-metastatic properties.
AB  - Treating metastasis has been challenging due to tumors complexity and
      heterogeneity. This complexity is partly related to the crosstalk between tumor
      and its microenvironment. Endothelial cells -the building blocks of tumor
      vasculature- have been shown to have additional roles in cancer progression than
      angiogenesis and supplying oxygen and nutrients. Here, we show an alternative
      role for endothelial cells in supporting breast cancer growth and spreading
      independent of their vascular functions. Using endothelial cells and breast
      cancer cell lines MDA-MB231 and MCF-7, we developed co-culture systems to study
      the influence of tumor endothelium on breast tumor development by both in vitro
      and in vivo approaches. Our results demonstrated that endothelial cells conferred
      survival advantage to tumor cells under complete starvation and enriched the
      CD44HighCD24Low/- stem cell population in tumor cells. Moreover, endothelial
      cells enhanced the pro-metastatic potential of breast cancer cells. The in vitro
      and in vivo results concordantly confirmed a role for endothelial Jagged1 to
      promote breast tumor through notch activation. Here, we propose a role for
      endothelial cells in enhancing breast cancer progression, stemness, and pro
      metastatic traits through a perfusion-independent manner. Our findings may be
      beneficial in developing novel therapeutic approaches. 

PMID- 25380490
TI  - Mass spectrometry studies of lycodine-type Lycopodium alkaloids: sauroxine and N
      demethylsauroxine.
AB  - RATIONALE: Sauroxine and N-demethylsauroxine are lycodine-type Lycopodium
      alkaloids. In recent years, Lycopodium alkaloids have gained significant interest
      due to their unique skeletal characteristics as well as due to their
      acetylcholinesterase activity. It is known that drugs that inhibit
      acetylcholinesterase can be used to treat the early stages of Alzheimer's
      disease. METHODS: Sauroxine and N-demethylsauroxine were isolated from the aerial
      parts of Huperzia saururus (Lam.) Trevis. Electron ionization mass spectrometry
      (EI-MS) (low resolution) and collision-induced dissociation tandem mass
      spectrometry (CID-MS/MS) fragmentation was conducted using an ion trap, GCQ Plus
      mass spectrometer with MS/MS. Electron ionization high-resolution mass
      spectrometry (EI-HRMS) was performed in a magnetic sector mass spectrometer
      (Micromass VG). RESULTS: Using GC/EI-CID-MS/MS we obtained different
      fragmentation routes that connect all the ionic populations. In addition, the use
      of EI-HRMS allowed us to measure the exact masses of all the fragment ions, and,
      with all this information gathered, we tried to establish a fragmentation scheme
      concordant with the ascendant and descendant species. CONCLUSIONS: The mass
      spectrometry studies presented in this work complete our mass studies of
      Lycopodium alkaloids. The mass spectrometry work presented has been very useful
      to confirm the structures as well as to support the biogenetic relationships
      between the lycodine-type Lycopodium alkaloids: sauroxine and N
      demethylsauroxine.

PMID- 25380489
TI  - Studies on quantitative phosphopeptide analysis by matrix-assisted laser
      desorption/ionization mass spectrometry without label, chromatography or
      calibration curves.
AB  - RATIONALE: Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry
      combined with isotope labeling methods are effective for protein and peptide
      quantification, but limited in their multiplexing capacity, cost-effectiveness
      and dynamic range. This study investigates MALDI-MS-based quantification of
      peptide phosphorylation without labeling, and aims to overcome the shot-to-shot
      variability of MALDI using a mathematical transformation and extended data
      acquisition times. METHODS: A linear relationship between the reciprocal of
      phosphopeptide mole fraction and the reciprocal of phosphorylated-to
      unphosphorylated signal ratio is derived, and evaluated experimentally using
      three separate phosphopeptide systems containing phosphorylated serine, threonine
      and tyrosine residues: mixtures of phosphopeptide and its des-phospho-analog with
      known stoichiometry measured by vacuum MALDI-linear ion trap mass spectrometry
      and fit to the linear model. The model is validated for quantifying in vitro
      phosphorylation assays with inhibition studies on Cdk2/cyclinA. RESULTS: Dynamic
      range of picomoles to femtomoles, good accuracy (deviations of 1.5-3.0% from
      expected values) and reproducibility (relative standard deviation (RSD) = 4.3
      6.3%) are achieved. Inhibition of cyclin-dependent kinase phosphorylation by the
      classical inhibitors olomoucine and r-roscovitine was evaluated and IC50 values
      found to be in agreement with reported literature values. These results, achieved
      with single-point calibration, without isotope or chromatography, compare
      favorably to those arrived at using isotope dilution (p > 0.5 for accuracy).
      CONCLUSIONS: The mathematical relationship derived here can be applied to a
      method that we term Double Reciprocal Isotope-free Phosphopeptide Quantification
      (DRIP-Q), as a strategy for quantification of in vitro phosphorylation assays,
      the first MALDI-based, isotope- and calibration curve-free method of its type.
      These results also pave the way for further systematic studies investigating the
      effect of peptide composition and experimental conditions on quantitative, label
      free MALDI.

PMID- 25380491
TI  - Post-acquisition analysis of untargeted accurate mass quadrupole time-of-flight
      MS(E) data for multiple collision-induced neutral losses and fragment ions of
      glutathione conjugates.
AB  - RATIONALE: Analytical methods to assess glutathione (GSH) conjugate formation
      based on mass spectrometry usually take advantage of the specific fragmentation
      behavior of the glutathione moiety. However, most methods used for GSH adduct
      screening monitor only one specific neutral loss or one fragment ion, even though
      the peptide moiety of GSH adducts shows a number of other specific neutral
      fragments and fragment ions which can be used for identification. METHODS: Nine
      reference drugs well known to form GSH adducts were incubated with human liver
      microsomes. Mass spectrometric analysis was performed with a quadrupole time-of
      flight mass spectrometer in untargeted accurate mass MS(E) mode. The data
      analysis and evaluation was achieved in an automated approach with software to
      extract and identify GSH conjugates based on the presence of multiple collision
      induced neutral losses and fragment ions specific for glutathione conjugates in
      the high-energy MS spectra. RESULTS: In total 42 GSH adducts were identified.
      Eight (18%) adducts did not show the neutral loss of 129 but were identified
      based on the appearance of other GSH-specific neutral losses or fragment ions. In
      high-energy MS(E) spectra the GSH-specific fragment ions of m/z 308 and 179 as
      well as the neutral loss of 275 Da were complementary to the commonly used
      neutral loss of 129 Da. Further, one abundant (yet unpublished) GSH conjugate of
      troglitazone formed in human liver microsomes was found. CONCLUSIONS: A software
      aided approach was developed to reliably retrieve GSH adduct formation data out
      of untargeted complex full scan QTOFMS(E) data in a fast and efficient way. The
      present approach to detect and analyze multiple collision-induced neutral losses
      and fragment ions of glutathione conjugates in untargeted MS(E) data might be
      applicable to higher throughput to assess reactive metabolite formation in drug
      discovery.

PMID- 25380492
TI  - Rapid, high-precision measurements of boron isotopic compositions in marine
      carbonates.
AB  - RATIONALE: The isotopic composition and elemental abundance of boron (B) in
      marine carbonates provide a powerful tool for tracking changes in seawater pH and
      carbonate chemistry. Progress in this field has, however, been hampered by the
      volatile nature of B, its persistent memory, and other uncertainties associated
      with conventional chemical extraction and mass spectrometric measurements. Here
      we show that for marine carbonates, these limitations can be overcome by using a
      simplified, low-blank, chemical extraction technique combined with robust multi
      collector inductively couple plasma mass spectrometry (MC-ICPMS) methods.
      METHODS: Samples are dissolved in dilute HNO3 and loaded first onto on a cation
      exchange column with the major cations (Ca, Mg, Sr, Na) being quantitatively
      retained while the B fraction is carried in the eluent. The eluent is then passed
      directly through an anion column ensuring that any residual anions, such as SO4(2
      ), are removed. Isotopic measurements of (11)B/(10)B ratios are undertaken by
      matching both the B concentration and the isotopic compositions of the samples
      with the bracketing standard, thereby minimising corrections for cross
      contamination. RESULTS: The veracity of the MC-ICPMS procedure is demonstrated
      using a gravimetrically prepared laboratory standard, UWA24.7, relative to the
      international reference standard NIST SRM 951 (delta(11)B = 00/00). This gives
      values consistent with gravimetry (delta(11)B = 24.7 +/- 0.30/00 2sd) for
      solutions ranging in concentration from 50 to 500 ppb, equivalent to ~2-10 mg
      size coral samples. The overall integrity of the method for carbonate analysis is
      demonstrated by measurements of the international carbonate standard JCp-1
      (delta(11)B = 24.3 +/- 0.340/00 2sd). CONCLUSIONS: A streamlined, integrated
      approach is described here that enables rapid, accurate, high-precision
      measurements of boron isotopic compositions and elemental abundances in commonly
      analysed biogenic carbonates, such as corals, bivalves, and large benthic forams.
      The overall simplicity of this robust approach should greatly facilitate the
      wider application of boron isotope geochemistry, especially to marine carbonates.

PMID- 25380493
TI  - Identification of xenobiotic metabolites from biological fluids using flow
      injection analysis high-resolution mass spectrometry and post-acquisition data
      filtering.
AB  - RATIONALE: Concern for public health entails the need to evaluate the degree of
      exposure of population to toxicants. To do this, robust high-throughput
      approaches are required to be able to perform a large number of analyses in
      cohort studies. In this study, a data-filtering procedure was applied to mass
      spectral data acquired by direct analysis of biological fluids leading to rapid
      detection of metabolites in a model xenobiotic system. METHODS: Flow injection
      analysis (FIA) coupled to negative electrospray ionization (ESI)-LTQ Orbitrap
      Fourier transform mass spectrometry was used to directly analyze urine of rats
      treated with vinclozolin. Tandem mass spectrometry (MS/MS) experiments were
      subsequently performed for confirmation of a new metabolite structure. The
      isotope filtering based on the difference between accurate masses of (35)Cl and
      (37)Cl was applied to the raw data for the specific detection of ions containing
      at least one chlorine atom. RESULTS: Seven metabolites of vinclozolin were
      manually identified thanks to the characteristic isotope pattern of dichlorinated
      compounds. A new metabolite of vinclozolin was detected for the first time and
      identified as a sulfate conjugate. The application of an isotope-filtering
      procedure allowed the selective extraction of pertinent signals from the data.
      The processed mass spectrum was greatly simplified, significantly facilitating
      the detection of the seven metabolites previously identified. CONCLUSIONS: The
      use of FIA-HRMS in combination with dedicated bio-informatics data processing is
      shown to be an efficient approach for the rapid detection of metabolites in
      biological fluids. This is a very promising high-throughput approach for rapid
      characterization of the exposure status to xenobiotics.

PMID- 25380495
TI  - Radical-directed dissociation of peptides and proteins by infrared multiphoton
      dissociation and sustained off-resonance irradiation collision-induced
      dissociation with Fourier transform ion cyclotron resonance mass spectrometry.
AB  - RATIONALE: Recent experiments utilizing photodissociation in linear ion traps
      have enabled significant development of Radical-Directed Dissociation (RDD) for
      the examination of peptides and proteins. The increased mass accuracy and
      resolution available in Fourier transform ion cyclotron resonance mass
      spectrometry (FTICR-MS) should enable further progress in this area. Preliminary
      experiments with photoactivated radicals are reported herein. METHODS: A 266 nm
      Nd:YAG laser is coupled to a FTICR or linear ion trap mass spectrometer. Radical
      peptides and proteins are generated by ultraviolet photodissociation (PD) and
      further activated by collisions or infrared photons. RESULTS: A 266 nm UV laser
      and an IR laser can be simultaneously coupled to a 15 Tesla FTICR mass
      spectrometer. The ultra-low-pressure environment in FTICR-MS makes collisional
      cooling less competitive, and thus more secondary fragments are generated by UVPD
      than in linear ion traps. Activation by sustained off-resonance irradiation
      collision-induced dissociation (SORI-CID) or infrared multiphoton dissociation
      (IRMPD) also yields additional secondary fragmentation relative to CID in an ion
      trap. Accurate identification of RDD fragments is possible in FTICR-MS.
      CONCLUSIONS: Relative to linear ion trap instruments, PD experiments in FTICR-MS
      are more difficult to execute due to poor ion cloud overlap and the low pressure
      environment. However, the results can be more easily interpreted due to the
      increased resolution and mass accuracy.

PMID- 25380494
TI  - A rapid, sensitive and solvent-less method for determination of malonaldehyde in
      meat by stir bar sorptive extraction coupled thermal desorption and gas
      chromatography/mass spectrometry with in situ derivatization.
AB  - RATIONALE: The traditional methods for analysis of malonaldehyde (MDA), such as
      the thiobarbituric acid (TBA) assay, require strong acidity at high temperature
      for derivatization and lack specificity in analysis. Stir bar sorptive extraction
      (SBSE) coupled with thermal desorption-gas chromatography/mass spectrometry (TD
      GC/MS) with in situ derivatization using pentafluorophenylhydrazine (PFPH) under
      mild conditions is an emerging technique for MDA analysis. METHODS: MDA in meat
      was derivatized with PFPH at pH ~4 for 1 h at room temperature, forming a
      relative stable derivative of MDA-PFPH. The derivative of MDA-PFPH was
      simultaneously extracted using SBSE. Then, MDA-PFPH was thermally released and
      quantitatively analyzed by GC/MS in selected ion monitoring (SIM) mode. RESULTS:
      The method of SBSE-TD-GC/MS for MDA analysis with in situ derivatization was
      optimized and validated with good linearity, specificity and limit of
      detection/quantification (LOD/LOQ). The method was successfully applied for
      analysis of MDA in raw and cooked meat (pork). CONCLUSIONS: The SBSE-TD-GC/MS
      method was suitable to monitor and analyze MDA in meat samples at trace levels.
      The simple, sensitive and solvent-less method with moderated in situ
      derivatization can be applied for analysis of MDA in a wide variety of foods and
      biological samples.

PMID- 25380496
TI  - Enzymatic generation of peptides flanked by basic amino acids to obtain MS/MS
      spectra with 2* sequence coverage.
AB  - RATIONALE: Tandem mass (MS/MS) spectra generated by collision-induced
      dissociation (CID) typically lack redundant peptide sequence information in the
      form of e.g. b- and y-ion series due to frequent use of sequence-specific
      endopeptidases cleaving C- or N-terminal to Arg or Lys residues. METHODS: Here we
      introduce arginyl-tRNA protein transferase (ATE, EC 2.3.2.8) for proteomics. ATE
      recognizes acidic amino acids or oxidized Cys at the N-terminus of a substrate
      peptide and conjugates an arginine from an aminoacylated tRNA(Arg) onto the N
      terminus of the substrate peptide. This enzymatic reaction is carried out under
      physiological conditions and, in combination with Lys-C/Asp-N double digest,
      results in arginylated peptides with basic amino acids on both termini. RESULTS:
      We demonstrate that in vitro arginylation of peptides using yeast arginyl tRNA
      protein transferase 1 (yATE1) is a robust enzymatic reaction, specific to only
      modifying N-terminal acidic amino acids. Precursors originating from arginylated
      peptides generally have an increased protonation state compared with their non
      arginylated forms. Furthermore, the product ion spectra of arginylated peptides
      show near complete 2* fragment ladders within the same MS/MS spectrum using
      commonly available electrospray ionization peptide fragmentation modes.
      Unexpectedly, arginylated peptides generate complete y- and c-ion series using
      electron transfer dissociation (ETD) despite having an internal proline residue.
      CONCLUSIONS: We introduce a rapid enzymatic method to generate peptides flanked
      on either terminus by basic amino acids, resulting in a rich, redundant MS/MS
      fragment pattern.

PMID- 25380498
TI  - Generation of new Agm Ten clusters via laser ablation synthesis using Ag-Te nano
      composite as precursor. Quadrupole ion trap time-of-flight mass spectrometry.
AB  - RATIONALE: Silver tellurides find applications in the development of infrared
      detection, imaging, magnetics, sensors, memory devices, and optic materials.
      However, only a limited number of silver tellurides have been described to date.
      Laser ablation synthesis (LAS) was selected to generate new Ag-Te clusters.
      METHODS: Isothermal adsorption was used to study the formation of silver nano
      particles-tellurium aggregates. Laser desorption ionization quadrupole ion trap
      time-of-flight mass spectrometry (LDI-QIT-TOFMS) was used for the generation and
      analysis of Agm Ten clusters. Scanning electron microscopy and energy-dispersive
      X-ray spectroscopy were used to visualize the structure of materials. The
      stoichiometry of the generated clusters was determined by computer modeling of
      isotopic patterns. RESULTS: A simple, one-pot method for the preparation of Ag-Te
      nano-composite was developed and found suitable for LAS of silver tellurides. The
      LDI of Ag-Te nano-composite leads to the formation of 11 unary and 52 binary
      clusters. The stoichiometry of the 34 novel Agm Ten clusters is reported here for
      the first time. CONCLUSIONS: LAS with TOFMS detection was proven to be a powerful
      technique for the generation of silver telluride clusters. Knowledge of the
      stoichiometry of the generated clusters might facilitate the further development
      of novel high-tech silver tellurium nano-materials.

PMID- 25380497
TI  - Effects of decalcification on bulk and compound-specific nitrogen and carbon
      isotope analyses of dentin.
AB  - RATIONALE: For bulk carbon and nitrogen isotope analysis of dentin, samples are
      typically decalcified. Since the non-protein carbon in dentin is low, whole
      sample analysis may produce reliable data. Compound-specific isotope analysis
      (CSIA) of bone and tooth dentin protein is a powerful tool for reconstructing the
      flow of carbon and nitrogen in modern and past food webs. Decalcification has
      also been used to prepare bone and dentin samples for CSIA, but the effects of
      this process on bulk dentin, amino acid composition, and their specific isotope
      values are not known. METHODS: The bulk isotope values of raw and decalcified
      dentin from a sperm whale tooth were measured to determine the effects of
      decalcification and the accuracy of untreated dentin results. CSIA was also
      performed on decalcified and raw dentin to examine differences in the amino acid
      isotope values and molar composition between these two approaches. RESULTS:
      Analysis of raw dentin yields precise and accurate bulk isotope measurements for
      this animal. The isotopic values of decalcified samples and raw dentin for
      individual amino acids were similar, but the average of the isotope value offsets
      between the two sample types was significant. The presence of inorganic material
      complicated raw sample processing for individual amino acid isotope values, and
      may have contributed to the isotopic differences between decalcified and raw
      samples. CONCLUSIONS: Decalcification is not needed to measure bulk isotope
      values in dentin from this modern odontocete, probably because the lipid and
      carbonate concentrations are low and the carbon isotope values of dentin protein
      and carbonate are similar. This method should not be applied in some cases (e.g.,
      with fossil dentin and modern bone). Decalcification should still be used prior
      to CSIA since significant matrix issues occur with raw dentin processing and
      decalcification does not alter the amino acid molar composition or isotopic
      values of dentin.

PMID- 25380499
TI  - Formation of the [M+Cu+4Cl]+ ion under laser desorption ionization conditions as
      a result of Cl addition to a C = C bond (M - methyl or ethyl ester of 3,5
      bis(2,2'-bipyridin-4-ylethynyl)benzoic acid).

PMID- 25380500
TI  - Odd-even effects in charge transport across n-alkanethiolate-based SAMs.
AB  - This paper compares rates of charge transport across self-assembled monolayers
      (SAMs) of n-alkanethiolates having odd and even numbers of carbon atoms (nodd and
      neven) using junctions with the structure M(TS)/SAM//Ga2O3/EGaIn (M = Au or Ag).
      Measurements of current density, J(V), across SAMs of n-alkanethiolates on Au(TS)
      and Ag(TS) demonstrated a statistically significant odd-even effect on Au(TS),
      but not on Ag(TS), that could be detected using this technique. Statistical
      analysis showed the values of tunneling current density across SAMs of n
      alkanethiolates on Au(TS) with nodd and neven belonging to two separate sets, and
      while there is a significant difference between the values of injection current
      density, J0, for these two series (log|J0Au,even| = 4.0 +/- 0.3 and log|J0Au,odd|
      = 4.5 +/- 0.3), the values of tunneling decay constant, beta, for nodd and neven
      alkyl chains are indistinguishable (betaAu,even = 0.73 +/- 0.02 A(-1), and
      betaAu,odd= 0.74 +/- 0.02 A(-1)). A comparison of electrical characteristics
      across junctions of n-alkanethiolate SAMs on gold and silver electrodes yields
      indistinguishable values of beta and J0 and indicates that a change that
      substantially alters the tilt angle of the alkyl chain (and, therefore, the
      thickness of the SAM) has no influence on the injection current density across
      SAMs of n-alkanethiolates. 

PMID- 25380502
TI  - Variation in predictive ability of common genetic variants by established strata:
      the example of breast cancer and age.
AB  - BACKGROUND: Recent studies of breast cancer and common genetic markers have
      failed to identify pervasive gene-gene and gene-environment interactions.
      Theoretical considerations also suggest that the contribution of modest
      interactions to risk discrimination in the general population is likely small.
      However, the clinical utility of common breast cancer risk markers may
      nonetheless differ across strata defined by known risk factors, such as age.
      METHODS: We examined the age-specific per-allele odds ratios of 15 common single
      nucleotide polymorphisms (SNPs) found to be associated with breast cancer in 1142
      breast cancer cases and 1145 controls from the Nurses' Health Study. We
      calculated the age-specific discriminatory ability of risk models incorporating
      these SNPs. We then conducted simulation studies to explore how hypothetical
      underlying genetic models may fit the observed results. RESULTS: Although all
      individual SNP-by-age interactions were modest, we found a negative interaction
      effect between age and a genetic risk score defined by the sum of risk alleles (P
      = 0.04). We also observed a decrease in discriminatory ability, as measured by
      the area under the curve (AUC), of the SNPs with age (P = 0.04). Simulation
      studies revealed models where the AUC can differ by strata defined by a risk
      factor without the presence of interactions; however, our study suggests that the
      observed differences in AUC are explained by the age-specific effect of the SNPs.
      CONCLUSION: The identification of risk factors that alter the effect of multiple
      genetic variants can help to explain the genetic architecture of multifactorial
      diseases and identify subgroups of persons who may benefit from genetic
      screening.

PMID- 25380504
TI  - Sandmeyer difluoromethylation of (hetero-)arenediazonium salts.
AB  - A Sandmeyer-type difluoromethylation process has been developed that allows the
      straightforward conversion of (hetero-)arenediazonium salts into the
      corresponding difluoromethyl (hetero-)arenes under mild conditions. The actual
      difluoromethylating reagent, a difluoromethyl-copper complex, is formed in situ
      from copper thiocyanate and TMS-CF2H. The diazonium salts are either preformed or
      generated in situ from broadly available aromatic amines. 

PMID- 25380501
TI  - Modulation of non steroidal anti-inflammatory drug induced membrane fusion by
      copper coordination of these drugs: anchoring effect.
AB  - Membrane fusion, an integral event in several biological processes, is
      characterized by several intermediate steps guided by specific energy barriers.
      Hence, it requires the aid of fusogens to complete the process. Common fusogens,
      such as proteins/peptides, have the ability to overcome theses barriers by their
      conformational reorganization, an advantage not shared by small drug molecules.
      Hence, drug induced fusion at physiologically relevant drug concentrations is
      rare and occurs only in the case of the oxicam group of non steroidal anti
      inflammatory drugs (NSAIDs). To use drugs to induce and control membrane fusion
      in various biochemical processes requires the understanding of how different
      parameters modulate fusion. Also, fusion efficacy needs to be enhanced. Here we
      have synthesized and used Cu(II) complexes of fusogenic oxicam NSAIDs, Meloxicam
      and Piroxicam, to induce fusion in model membranes monitored by using DSC, TEM,
      steady-state, and time-resolved spectroscopy. The ability of the complexes to
      anchor apposing model membranes to initiate/facilitate fusion has been
      demonstrated. This results in better fusion efficacy compared to the bare drugs.
      These complexes can take the fusion to its final step. Unlike other designed
      membrane anchors, the role of molecular recognition and strength of interaction
      between molecular partners is obliterated for these preformed Cu(II)-NSAIDs. 

PMID- 25380503
TI  - Estimating seroprevalence of human papillomavirus type 16 using a mixture model
      with smoothed age-dependent mixing proportions.
AB  - BACKGROUND: The presence in serum of antibodies to viral antigens is generally
      considered a well-defined marker of past infection or vaccination. However,
      analyses of serological data that use a cut-off value to classify individuals as
      seropositive are prone to misclassification bias, in particular when studying
      infections with a weak serological response, such as the sexually transmitted
      human papillomavirus (HPV). METHODS: We analyzed the serological concentrations
      of HPV type 16 (HPV16) antibodies in the general Dutch population in 2006-2007,
      before the introduction of mass vaccination against HPV. We used a 2-component
      mixture model to represent persons who were seronegative or seropositive for
      HPV16. Component densities were assumed to be log-normally distributed, with
      parameters possibly dependent on sex. The age-dependent mixing proportions were
      smoothed using penalized splines to obtain a flexible seroprevalence profile.
      RESULTS: Our results suggest that HPV16 seropositivity is associated with higher
      antibody concentrations in women as compared with men. Seroprevalence shows an
      increase starting from adolescence in men and women alike, coinciding with the
      age of sexual debut. Seroprevalence stabilizes in men around age 40, whereas it
      has a decreasing trend from age 50 onwards in women. Analyses that rely on a cut
      off value to classify persons as seropositive yield substantially different
      seroprevalence profiles, leading to a qualitatively different interpretation of
      HPV16 infection dynamics. CONCLUSIONS: Our results provide a benchmark for
      examining the effect of HPV16 vaccination in future serological surveys. Our
      method may prove useful for estimating seroprevalence of other infections with a
      weak serological response.

PMID- 25380505
TI  - Fixed-gap tunnel junction for reading DNA nucleotides.
AB  - Previous measurements of the electronic conductance of DNA nucleotides or amino
      acids have used tunnel junctions in which the gap is mechanically adjusted, such
      as scanning tunneling microscopes or mechanically controllable break junctions.
      Fixed-junction devices have, at best, detected the passage of whole DNA molecules
      without yielding chemical information. Here, we report on a layered tunnel
      junction in which the tunnel gap is defined by a dielectric layer, deposited by
      atomic layer deposition. Reactive ion etching is used to drill a hole through the
      layers so that the tunnel junction can be exposed to molecules in solution. When
      the metal electrodes are functionalized with recognition molecules that capture
      DNA nucleotides via hydrogen bonds, the identities of the individual nucleotides
      are revealed by characteristic features of the fluctuating tunnel current
      associated with single-molecule binding events. 

PMID- 25380507
TI  - Carbon stock loss from deforestation through 2013 in Brazilian Amazonia.
AB  - The largest carbon stock in tropical vegetation is in Brazilian Amazonia. In this
      ~5 million km(2) area, over 750,000 km(2) of forest and ~240,000 km(2) of
      nonforest vegetation types had been cleared through 2013. We estimate current
      carbon stocks and cumulative gross carbon loss from clearing of premodern
      vegetation in Brazil's 'Legal Amazonia' and 'Amazonia biome' regions. Biomass of
      'premodern' vegetation (prior to major increases in disturbance beginning in the
      1970s) was estimated by matching vegetation classes mapped at a scale of 1 :
      250,000 and 29 biomass means from 41 published studies for vegetation types
      classified as forest (2317 1-ha plots) and as either nonforest or contact zones
      (1830 plots and subplots of varied size). Total biomass (above and below-ground,
      dry weight) underwent a gross reduction of 18.3% in Legal Amazonia (13.1 Pg C)
      and 16.7% in the Amazonia biome (11.2 Pg C) through 2013, excluding carbon loss
      from the effects of fragmentation, selective logging, fires, mortality induced by
      recent droughts and clearing of forest regrowth. In spite of the loss of carbon
      from clearing, large amounts of carbon were stored in stands of remaining
      vegetation in 2013, equivalent to 149 Mg C ha(-1) when weighted by the total area
      covered by each vegetation type in Legal Amazonia. Native vegetation in Legal
      Amazonia in 2013 originally contained 58.6 Pg C, while that in the Amazonia biome
      contained 56 Pg C. Emissions per unit area from clearing could potentially be
      larger in the future because previously cleared areas were mainly covered by
      vegetation with lower mean biomass than the remaining vegetation. Estimates of
      original biomass are essential for estimating losses to forest degradation. This
      study offers estimates of cumulative biomass loss, as well as estimates of
      premodern carbon stocks that have not been represented in recent estimates of
      deforestation impacts.

PMID- 25380506
TI  - Biochemical and structural analysis of inhibitors targeting the ADC-7
      cephalosporinase of Acinetobacter baumannii.
AB  - beta-Lactam resistance in Acinetobacter baumannii presents one of the greatest
      challenges to contemporary antimicrobial chemotherapy. Much of this resistance to
      cephalosporins derives from the expression of the class C beta-lactamase enzymes,
      known as Acinetobacter-derived cephalosporinases (ADCs). Currently, beta
      lactamase inhibitors are structurally similar to beta-lactam substrates and are
      not effective inactivators of this class C cephalosporinase. Herein, two boronic
      acid transition state inhibitors (BATSIs S02030 and SM23) that are chemically
      distinct from beta-lactams were designed and tested for inhibition of ADC
      enzymes. BATSIs SM23 and S02030 bind with high affinity to ADC-7, a chromosomal
      cephalosporinase from Acinetobacter baumannii (Ki = 21.1 +/- 1.9 nM and 44.5 +/-
      2.2 nM, respectively). The X-ray crystal structures of ADC-7 were determined in
      both the apo form (1.73 A resolution) and in complex with S02030 (2.0 A
      resolution). In the complex, S02030 makes several canonical interactions: the O1
      oxygen of S02030 is bound in the oxyanion hole, and the R1 amide group makes key
      interactions with conserved residues Asn152 and Gln120. In addition, the
      carboxylate group of the inhibitor is meant to mimic the C3/C4 carboxylate found
      in beta-lactams. The C3/C4 carboxylate recognition site in class C enzymes is
      comprised of Asn346 and Arg349 (AmpC numbering), and these residues are conserved
      in ADC-7. Interestingly, in the ADC-7/S02030 complex, the inhibitor carboxylate
      group is observed to interact with Arg340, a residue that distinguishes ADC-7
      from the related class C enzyme AmpC. A thermodynamic analysis suggests that
      DeltaH driven compounds may be optimized to generate new lead agents. The ADC
      7/BATSI complex provides insight into recognition of non-beta-lactam inhibitors
      by ADC enzymes and offers a starting point for the structure-based optimization
      of this class of novel beta-lactamase inhibitors against a key resistance target.

PMID- 25380508
TI  - Endoscopic sleeve gastroplasty for the treatment of obesity.
AB  - BACKGROUND AND STUDY AIMS: Emerging endoscopic techniques are minimally invasive
      and can mimic the anatomic alterations achieved by surgical sleeve gastrectomy.
      The objective of this study was to evaluate endoscopic sleeve gastroplasty.
      PATIENTS AND METHODS: This was a prospective, single-center study of 20 patients
      who underwent flexible endoscopic suturing for endoluminal gastric volume
      reduction. A multidisciplinary team provided postprocedure care. Patient status
      and weight were recorded at baseline, and at 1, 3, and 6 months after the
      procedure. RESULTS: There were no adverse events and all patients were discharged
      in less than 24 hours. Baseline mean body mass index was 38.5 kg/m(2), and mean
      age was 45.8 years. Initial body weight (108.5 +/- 14.9 kg) was significantly
      reduced. Following the procedure, the mean body weight reduction was 8.2 +/- 2.5
      kg at 1 month (% of initial weight loss 7.6 %; P < 0.05), 13.6 +/- 4.8 kg at 3
      months (12.4 % weight loss; P < 0.05), and 19.3 +/- 8.9 kg at 6 months (17.8 %
      weight loss; P < 0.05). CONCLUSION: Endoscopic sleeve gastroplasty can be
      effective for the treatment of patients with obesity.

PMID- 25380510
TI  - Initial experience with endoscopic sleeve gastroplasty: technical success and
      reproducibility in the bariatric population.
AB  - BACKGROUND AND AIMS: Novel endoscopic techniques have been developed as effective
      treatments for obesity. Recently, reduction of gastric volume via endoscopic
      placement of full-thickness sutures, termed endoscopic sleeve gastroplasty (ESG),
      has been described. Our aim was to evaluate the safety, technical feasibility,
      and clinical outcomes for ESG. PATIENT AND METHODS: Between August 2013 and May
      2014, ESG was performed on 10 patients using an endoscopic suturing device. Their
      weight loss, waist circumference, and clinical outcomes were assessed. RESULTS:
      Mean patient age was 43.7 years and mean body mass index (BMI) was 45.2 kg/m(2).
      There were no significant adverse events noted. After 1 month, 3 months, and 6
      months, excess weight loss of 18 %, 26 %, and 30 %, and mean weight loss of 11.5
      kg, 19.4 kg, and 33.0 kg, respectively, were observed. The differences observed
      in mean BMI and waist circumference were 4.9 kg/m(2) (P = 0.0004) and 21.7 cm (P
      = 0.003), respectively. CONCLUSIONS: ESG is effective in achieving weight loss
      with minimal adverse events. This approach may provide a cost-effective
      outpatient procedure to add to the steadily growing armamentarium available for
      treatment of this significant epidemic.

PMID- 25380509
TI  - Endoscopic full-thickness resection of gastric subepithelial tumors: a single
      center series.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic full-thickness resection of gastric
      subepithelial tumors with a full-thickness suturing device has been described as
      feasible in two small case series. The aim of this study was to evaluate the
      efficacy, safety, and clinical outcome of this resection technique. PATIENTS AND
      METHODS: After 31 patients underwent endoscopic full-thickness resection, the
      data were analyzed retrospectively. Before snare resection, 1 to 3 full-thickness
      sutures were placed underneath each tumor with a device originally designed for
      endoscopic anti-reflux therapy. RESULTS: All tumors were resected successfully.
      Bleeding occurred in 12 patients (38.7 %); endoscopic hemostasis could be
      achieved in all cases. Perforation occurred in 3 patients (9.6 %), and all
      perforations could be managed endoscopically. Complete resection was
      histologically confirmed in 28 of 31 patients (90.3 %). Mean follow-up was 213
      days (range, 1 - 1737), and no tumor recurrences were observed. CONCLUSION:
      Endoscopic full-thickness resection of gastric subepithelial tumors with the
      suturing technique described above is feasible and effective. After the resection
      of gastrointestinal stromal tumors (GISTs), we did not observe any recurrences
      during follow-up, indicating that endoscopic full-thickness resection may be an
      alternative to surgical resection for selected patients.

PMID- 25380512
TI  - Naphthalene diimides as red fluorescent pH sensors for functional cell imaging.
AB  - A small library of hydrosoluble naphthalene diimides (NDIs) was designed and
      synthesized, as cell permeable pH "turned-on" fluorescent sensors, for cellular
      applications. The NDIs exhibit a non-emitting twisted intramolecular charge
      transfer (TICT) state, which has been described by a DFT computational
      investigation. These NDIs do not emit as a free base, but they become strong
      emitters when protonated. Switching of the red emission was achieved in the pH
      window 2.5-6, tuning steric and electronic features of the amine moiety. The
      least acidic protonated NDI (pKa 5.1), was investigated in normal and cancer
      cells. Its selective redistribution in cancer cells from acidic vesicular
      organelles to the cytoplasm and the nucleus describes an effective application of
      these NDIs as a valuable functional tool. 

PMID- 25380511
TI  - A multidisciplinary consensus document on follow-up strategies for patients
      treated with percutaneous coronary intervention.
AB  - The number of percutaneous coronary interventions (PCI) is increasing worldwide.
      Follow-up strategies after PCI are extremely heterogeneous and can greatly affect
      the cost of medical care. Of note, clinical evaluations and non-invasive exams
      are often performed to low risk patients. In the present consensus document,
      practical advises are provided with respect to a tailored follow-up strategy on
      the basis of patients' risk profile. Three strategies follow-up have been defined
      and types and timing of clinical and instrumental evaluations are reported.
      Clinical and interventional cardiologists, cardiac rehabilitators, and general
      practitioners, who are in charge to manage post-PCI patients, equally contributed
      to the creation of the present document.

PMID- 25380513
TI  - Micellization of antineoplastic agent to significantly upregulate efficacy and
      security.
AB  - The amphiphilic diblock copolymer composed of methoxy poly(ethylene glycol) and
      racemic oligoleucine was synthesized which formed into micelle with uniform size
      in aqueous environment. Doxorubicin (DOX) was loaded into micelle aided by
      noncovalent interactions with high drug loading efficiency. The DOX-loaded
      micelle (referred as M-DOX) demonstrated the sustained drug release in vitro and
      excellent antiproliferative capability toward both MG63 and Saos-2 cells.
      Furthermore, for both MG63 and Saos-2-xenografted BALB/c nude mouse models, M-DOX
      exhibited enhanced intratumoral distribution, improved antitumor efficacy, and
      reduced side effects compared with free DOX. Therefore, the polypeptide micelle
      showed a bright prospect for controlled delivery of antitumor drugs in vivo. 

PMID- 25380514
TI  - Highly diastereo- and enantioselective construction of a
      spiro[cyclopenta[b]indole-1,3'-oxindole] scaffold via catalytic asymmetric formal
      [3+2] cycloadditions.
AB  - An organocatalytic asymmetric formal [3+2] cycloaddition of isatin-derived 3
      indolylmethanol with 3-methyl-2-vinylindole has been established, leading to
      highly stereoselective construction of a spiro[cyclopenta[b]indole-1,3'-oxindole]
      scaffold with the concomitant creation of three contiguous stereogenic centers
      (72-99% yield, all >95 : 5 dr, 90-98% ee), one of which is an all-carbon
      quaternary stereogenic center. 

PMID- 25380515
TI  - Altered behavior, physiology, and metabolism in fish exposed to polystyrene
      nanoparticles.
AB  - The use of nanoparticles in consumer products, for example, cosmetics,
      sunscreens, and electrical devices, has increased tremendously over the past
      decade despite insufficient knowledge about their effects on human health and
      ecosystem function. Moreover, the amount of plastic waste products that enter
      natural ecosystems, such as oceans and lakes, is increasing, and degradation of
      the disposed plastics produces smaller particles toward the nano scale.
      Therefore, it is of utmost importance to gain knowledge about how plastic
      nanoparticles enter and affect living organisms. Here we have administered 24 and
      27 nm polystyrene nanoparticles to fish through an aquatic food chain, from algae
      through Daphnia, and studied the effects on behavior and metabolism. We found
      severe effects on feeding and shoaling behavior as well as metabolism of the
      fish; hence, we conclude that polystyrene nanoparticles have severe effects on
      both behavior and metabolism in fish and that commonly used nanosized particles
      may have considerable effects on natural systems and ecosystem services derived
      from them. 

PMID- 25380516
TI  - Shape transformations of toroidal vesicles.
AB  - Morphologies of genus-1 and 2 toroidal vesicles are studied numerically by
      dynamically triangulated membrane models and experimentally by confocal laser
      microscopy. Our simulation results reproduce shape transformations observed in
      our experiments well. At large reduced volumes of the genus-1 vesicles, obtained
      vesicle shapes agree with the previous theoretical prediction, in which
      axisymmetric shapes are assumed: double-necked stomatocyte, discoidal toroid, and
      circular toroid. However, for small reduced volumes, it is revealed that a non
      axisymmetric discoidal toroid and handled discocyte exist in thermal equilibrium
      in the parameter range, in which the previous theory predicts axisymmetric
      discoidal shapes. Polygonal toroidal vesicles and subsequent budding transitions
      are also found. The entropy caused by shape fluctuations slightly modifies the
      stability of the vesicle shapes. 

PMID- 25380517
TI  - Synthesis, biological evaluation, and 3D QSAR study of 2-methyl-4-oxo-3
      oxetanylcarbamic acid esters as N-acylethanolamine acid amidase (NAAA)
      inhibitors.
AB  - N-(2-Oxo-3-oxetanyl)carbamic acid esters have recently been reported to be
      noncompetitive inhibitors of the N-acylethanolamine acid amidase (NAAA)
      potentially useful for the treatment of pain and inflammation. In the present
      study, we further explored the structure-activity relationships of the carbamic
      acid ester side chain of 2-methyl-4-oxo-3-oxetanylcarbamic acid ester
      derivatives. Additional favorable features in the design of potent NAAA
      inhibitors have been found together with the identification of a single digit
      nanomolar inhibitor. In addition, we devised a 3D QSAR using the atomic property
      field method. The model turned out to be able to account for the structural
      variability and was prospectively validated by designing, synthesizing, and
      testing novel inhibitors. The fairly good agreement between predictions and
      experimental potency values points to this 3D QSAR model as the first example of
      quantitative structure-activity relationships in the field of NAAA inhibitors. 

PMID- 25380518
TI  - Single nanowire electrode electrochemistry of silicon anode by in situ atomic
      force microscopy: solid electrolyte interphase growth and mechanical properties.
AB  - Silicon nanowires (SiNWs) have attracted great attention as promising anode
      materials for lithium ion batteries (LIBs) on account of their high capacity and
      improved cyclability compared with bulk silicon. The interface behavior,
      especially the solid electrolyte interphase (SEI), plays a significant role in
      the performance and stability of the electrodes. We report herein an in situ
      single nanowire atomic force microscopy (AFM) method to investigate the interface
      electrochemistry of silicon nanowire (SiNW) electrode. The morphology and Young's
      modulus of the individual SiNW anode surface during the SEI growth were
      quantitatively tracked. Three distinct stages of the SEI formation on the SiNW
      anode were observed. On the basis of the potential-dependent morphology and
      Young's modulus evolution of SEI, a mixture-packing structural model was proposed
      for the SEI film on SiNW anode. 

PMID- 25380519
TI  - Tunable and rapid self-assembly of block copolymers using mixed solvent vapors.
AB  - Pattern generation of well-controlled block copolymers (BCPs) with a high Flory
      Huggins interaction parameter (chi) is important for applications in sub-20 nm
      nanolithography. We used mixed solvents of dimethylformamide (DMF) and toluene to
      control the morphology as well as the time to achieve the targeted morphology via
      self-assembly of BCPs. By precisely controlling the volume ratio of DMF and
      toluene, well-ordered line, honeycomb, circular hole, and lamellar nanostructures
      were obtained from a cylinder-forming poly(styrene-b-2-vinylpyridine) (PS-b-P2VP)
      BCP with high chi. Furthermore, a well-aligned 12 nm line pattern was
      successfully achieved in the guiding template within one minute using the mixed
      solvents. This practical method may also be applicable to self-assembly of other
      BCPs, providing more opportunities for the next-generation sub-10 nm lithography
      applications. 

PMID- 25380520
TI  - Cartilage oligomeric matrix protein gene multilayers inhibit osteogenic
      differentiation and promote chondrogenic differentiation of mesenchymal stem
      cells.
AB  - There are still many challenges to acquire the optimal integration of biomedical
      materials with the surrounding tissues. Gene coatings on the surface of
      biomaterials may offer an effective approach to solve the problem. In order to
      investigate the gene multilayers mediated differentiation of mesenchymal stem
      cells (MSCs), gene functionalized films of hyaluronic acid (HA) and lipid-DNA
      complex (LDc) encoding cartilage oligomeric matrix protein (COMP) were
      constructed in this study via the layer-by-layer self-assembly technique.
      Characterizations of the HA/DNA multilayered films indicated the successful build
      up process. Cells could be directly transfected by gene films and a higher
      expression could be obtained with the increasing bilayer number. The multilayered
      films were stable for a long period and DNA could be easily released in an
      enzymatic condition. Real-time polymerase chain reaction (RT-PCR) assay presented
      significantly higher (p<0.01) COMP expression of MSCs cultured with HA/COMP
      multilayered films. Compared with control groups, the osteogenic gene expression
      levels of MSCs with HA/COMP multilayered films were down-regulated while the
      chondrogenic gene expression levels were up-regulated. Similarly, the alkaline
      phosphatase (ALP) staining and Alizarin red S staining of MSCs with HA/COMP films
      were weakened while the alcian blue staining was enhanced. These results
      demonstrated that HA/COMP multilayered films could inhibit osteogenic
      differentiation and promote chondrogenic differentiation of MSCs, which might
      provide new insight for physiological ligament-bone healing.

PMID- 25380521
TI  - MicroRNAs associated with the efficacy of photodynamic therapy in biliary tract
      cancer cell lines.
AB  - Photodynamic therapy (PDT) is a palliative treatment option for unresectable
      hilar biliary tract cancer (BTC) showing a considerable benefit for survival and
      quality of life with few side effects. Currently, factors determining the
      cellular response of BTC cells towards PDT are unknown. Due to their multifaceted
      nature, microRNAs (miRs) are a promising analyte to investigate the cellular
      mechanisms following PDT. For two photosensitizers, Photofrin(r) and Foscan(r),
      the phototoxicity was investigated in eight BTC cell lines. Each cell line
      (untreated) was profiled for expression of n=754 miRs using TaqMan(r) Array Human
      MicroRNA Cards. Statistical analysis and bioinformatic tools were used to
      identify miRs associated with PDT efficiency and their putative targets,
      respectively. Twenty miRs correlated significantly with either high or low PDT
      efficiency. PDT was particularly effective in cells with high levels of clustered
      miRs 25-93*-106b and (in case of miR-106b) a phenotype characterized by high
      expression of the mesenchymal marker vimentin and high proliferation (cyclinD1
      and Ki67 expression). Insensitivity towards PDT was associated with high miR-200
      family expression and (for miR-cluster 200a/b-429) expression of differentiation
      markers Ck19 and Ck8/18. Predicted and validated downstream targets indicate
      plausible involvement of miRs 20a*, 25, 93*, 130a, 141, 200a, 200c and 203 in
      response mechanisms to PDT, suggesting that targeting these miRs could improve
      susceptibility to PDT in insensitive cell lines. Taken together, the miRNome
      pattern may provide a novel tool for predicting the efficiency of PDT and
      following appropriate functional verification-may subsequently allow for
      optimization of the PDT protocol.

PMID- 25380522
TI  - A microdeletion of chromosome 9q33.3 encompasses the entire LMX1B gene in a
      Chinese family with nail patella syndrome.
AB  - Nail patella syndrome (NPS) is an autosomal dominant disorder characterized by
      nail malformations, patellar apoplasia, or patellar hypoplasia. Mutations within
      the LMX1B gene are found in 85% of families with NPS; thus, this gene has been
      characterized as the causative gene of NPS. In this study, we identified a
      heterozygous microdeletion of the entire LMX1B gene using multiplex ligation
      dependent probe amplification (MLPA) in a Chinese family with NPS. The
      determination of the deletion breakpoints by Illumina genome-wide DNA analysis
      beadchip showed that the deletion was located in chromosome 9q33.3 and spanned
      about 0.66 Mb in size. This heterozygous deletion provides strong evidence for
      haploinsufficiency as the pathogenic mechanism of NPS. 

PMID- 25380526
TI  - Formation and yield of multi-walled carbon nanotubes synthesized via chemical
      vapour deposition routes using different metal-based catalysts of FeCoNiAl,
      CoNiAl and FeNiAl-LDH.
AB  - Multi-walled carbon nanotubes (MWCNTs) were prepared via chemical vapor
      deposition (CVD) using a series of different catalysts, derived from FeCoNiAl,
      CoNiAl and FeNiAl layered double hydroxides (LDHs). Catalyst-active particles
      were obtained by calcination of LDHs at 800  degrees C for 5 h. Nitrogen and
      hexane were used as the carrier gas and carbon source respectively, for
      preparation of MWCNTs using CVD methods at 800  degrees C. MWCNTs were allowed to
      grow for 30 min on the catalyst spread on an alumina boat in a quartz tube. The
      materials were subsequently characterized through X-ray diffraction, Fourier
      transform infrared spectroscopy, surface area analysis, field emission scanning
      electron microscopy and transmission electron microscopy. It was determined that
      size and yield of MWCNTs varied depending on the type of LDH catalyst precursor
      that is used during synthesis. MWCNTs obtained using CoNiAl-LDH as the catalyst
      precursor showed smaller diameter and higher yield compared to FeCoNiAl and
      FeNiAl LDHs. 

PMID- 25380527
TI  - Insights into the crystal-packing effects on the spin crossover of [Fe(II)(1
      bpp)](2+)-based materials.
AB  - Iron(II) complexes of the [Fe(II)(1-bpp2)](2+) type (1-bpp = 2,6-di(pyrazol-1
      yl)pyridine) have been intensively investigated in the context of crystal
      engineering of switchable materials because their spin-crossover (SCO) properties
      dramatically depend on the counterions. Here, by means of DFT + U calculations at
      the molecular and solid state levels we provide a rationale for the different SCO
      behaviour of the BF4(-) and ClO4(-) salts of the parent complex; the former
      features Fe(II) complexes with a regular coordination geometry and undergoes a
      spin transition, whereas the Fe(II) complexes of the latter adopt a distorted
      structure and remain in the high-spin state at all temperatures. The different
      SCO behaviour of both salts can be explained on the basis of a combination of
      thermodynamic and kinetic effects. The shape of the SCO units at high temperature
      is thermodynamically controlled by the intermolecular interactions between the
      SCO units and counterions within the crystal. The spin trapping at low
      temperatures in the ClO4(-) salt, in turn, is traced back to a kinetic effect
      because our calculations have revealed the existence of a more stable polymorph
      having SCO units in their low-spin state that feature a regular structure. From
      the computational point of view, it is the first time that the U parameter is
      fine-tuned on the basis of CASPT2 calculations, thereby enabling an accurate
      description of the energetics of the spin transition at both molecular and solid
      state levels.

PMID- 25380524
TI  - Microenvironment of tumor-draining lymph nodes: opportunities for liposome-based
      targeted therapy.
AB  - The World Health Organization (WHO) recently reported that the total number of
      global cancer cases in 2013 reached 14 million, a 10% rise since 2008, while the
      total number of cancer deaths reached 8.2 million, a 5.2% increase since 2008.
      Metastasis is the major cause of death from cancer, accounting for 90% of all
      cancer related deaths. Tumor-draining lymph nodes (TDLN), the sentinel nodes, are
      the first organs of metastasis in several types of cancers. The extent of
      metastasis in the TDLN is often used in disease staging and prognosis evaluation
      in cancer patients. Here, we describe the microenvironment of the TDLN and review
      the recent literature on liposome-based therapies directed to immune cells within
      the TDLN with the intent to target cancer cells. 

PMID- 25380525
TI  - Pressure overload-induced cardiac hypertrophy response requires janus kinase 2
      histone deacetylase 2 signaling.
AB  - Pressure overload induces cardiac hypertrophy through activation of Janus kinase
      2 (Jak2), however, the underlying mechanisms remain largely unknown. In the
      current study, we tested whether histone deacetylase 2 (HDAC2) was involved in
      the process. We found that angiotensin II (Ang-II)-induced re-expression of fetal
      genes (Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) in
      cultured cardiomyocytes was prevented by the Jak2 inhibitor AG-490 and HDAC2
      inhibitor Trichostatin-A (TSA), or by Jak2/HDAC2 siRNA knockdown. On the other
      hand, myocardial cells with Jak2 or HDAC2 over-expression were hyper-sensitive to
      Ang-II. In vivo, pressure overload by transverse aorta binding (AB) induced a
      significant cardiac hypertrophic response as well as re-expression of ANP and BNP
      in mice heart, which were markedly reduced by AG-490 and TSA. Significantly, AG
      490, the Jak2 inhibitor, largely suppressed pressure overload-/Ang-II-induced
      HDAC2 nuclear exportation in vivo and in vitro. Meanwhile, TSA or HDAC2 siRNA
      knockdown reduced Ang-II-induced ANP/BNP expression in Jak2 over-expressed H9c2
      cardiomyocytes. Together, these results suggest that HDAC2 might be a downstream
      effector of Jak2 to mediate cardiac hypertrophic response by pressure overload or
      Ang-II. 

PMID- 25380528
TI  - The role of pain-related anxiety in adolescents' disability and social
      impairment: ALSPAC data.
AB  - BACKGROUND: Anxiety, in particular pain-related anxiety, plays an important role
      in explaining the severity of pain complaints and pain-related disability in both
      adults and children with chronic pain. The fear-avoidance model (FAM) describes
      how pain-related anxiety plays a critical role in the maintenance of pain
      avoidance behaviour, which in turn influences pain-related disability. However,
      the FAM does not take into account broader aspects of adolescence, such as social
      functioning, which could be negatively impacted by anxiety. In addition, most
      studies examining the role of anxiety in pain have used small convenience or
      clinical samples. By using a large UK epidemiological database, this study
      investigated the associations between pain-related anxiety, disability and
      judgements of social impairment. METHODS: Participants (n = 856) with recurrent
      pain were selected from a larger epidemiological study (Avon Longitudinal Study
      of Parents and Children) of adolescents attending a research clinic at the age of
      17 (n = 5170). Adolescents completed a self-report questionnaire on pain-related
      anxiety, disability and perceived social impairment. RESULTS: High levels of pain
      related anxiety were associated with more disability. In girls, higher levels of
      pain-related anxiety were also related to the self-perception of greater
      impairment in social functioning compared with their peers. CONCLUSIONS: Pain
      related anxiety was associated with greater pain-related disability and impaired
      social functioning. Social functioning should be explored as an integral part of
      fear-avoidance models of adolescent chronic pain.

PMID- 25380529
TI  - Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents
      Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface
      Failure.
AB  - Limbal epithelial stem cell deficiency can cause blindness, but transplantation
      of these cells on a carrier such as human amniotic membrane can restore vision.
      Unfortunately, clinical graft manufacture using amnion can be inconsistent.
      Therefore, we have developed an alternative substrate, Real Architecture for 3D
      Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion.
      Epithelial organization is improved when human limbal fibroblasts (hLF) are
      incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to
      transdifferentiate into a pro-scarring cell type, which would be incompatible
      with therapeutic transplantation. The aim of this work was to assess the scarring
      phenotype of hLF in RAFT TEs in hLE+ and hLE- RAFT TEs and in nonairlifted and
      airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic
      conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as
      a pro-scarring positive control against which hLF were compared using surrogate
      scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen
      synthesis, alpha-smooth muscle actin (alpha-SMA) expression, and transforming
      growth factor-beta (TGF-beta) secretion. Normal hLF and dFib maintained different
      phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and
      alpha-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although
      TGF-beta1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal
      hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs
      and, therefore, may be safe to include in therapeutic RAFT TE, where they can
      support hLE, although in vivo work is required to confirm this. dFib RAFT TEs
      (used in this study as a positive control) may be useful toward the development
      of an ex vivo disease model of Oc-MMP. 

PMID- 25380523
TI  - Current experience in testing mitochondrial nutrients in disorders featuring
      oxidative stress and mitochondrial dysfunction: rational design of
      chemoprevention trials.
AB  - An extensive number of pathologies are associated with mitochondrial dysfunction
      (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed
      "mitochondrial nutrients" (MN), such as alpha-lipoic acid (ALA), Coenzyme Q10
      (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number
      of clinical trials, and this review is focused on the use of MN-based clinical
      trials. The papers reporting on MN-based clinical trials were retrieved in
      MedLine up to July 2014, and evaluated for the following endpoints: (a) treated
      diseases; (b) dosages, number of enrolled patients and duration of treatment; (c)
      trial success for each MN or MN combinations as reported by authors. The reports
      satisfying the above endpoints included total numbers of trials and frequencies
      of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports
      testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved
      testing double MN associations, while no report was found testing a triple MN
      combination. A total of 28 reports tested MN associations with "classical"
      antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed
      better outcomes than individual MN, suggesting forthcoming clinical studies. The
      criteria in study design and monitoring MN-based clinical trials are discussed. 

PMID- 25380532
TI  - Cardiac outcomes 3 years after screening for asymptomatic coronary artery disease
      in patients with type 2 diabetes: value of myocardial perfusion imaging and
      coronary calcium score.
AB  - OBJECTIVE: The aim of the study was to identify the possible association among
      myocardial perfusion imaging (MPI) variables, coronary calcium score (CCS), and
      adverse events at medium term in type 2 asymptomatic diabetes mellitus patients.
      MATERIALS AND METHODS: Patients who participated in a first study that included a
      stress-rest MPI and a CCS assessment were asked to take part in this study. The
      present study protocol required a control single-photon emission computerized
      tomography after 3 years. Forty-one patients gave their informed consent.
      RESULTS: Of the 41 patients, 13 (32%) showed perfusion defects at the initial
      MPI. Of them, at 3 years, five continued showing perfusion defects, whereas
      another two had new defects (incidence of ischemia of 17%). Thus, 61% of the
      initial positive MPIs were normal at 3 years (P=0.04). In these cases the therapy
      was modified between the two studies. Left ventricular ejection fraction at
      stress showed a slight increase at 3 years (P=NS). Ventricular volumes
      significantly decreased at 3 years (P<0.01). Three patients (7.3%) developed an
      event during the follow-up (FU): two noncardiac deaths and one non-ST elevation
      myocardial infarction. The only variables that showed a possible association with
      the occurrence of events at FU were a CCS higher than 100 and less than 5
      metabolic equivalents (METS) reached during the stress test (P=0.01). CONCLUSION:
      A CCS higher than 100 and a low functional capacity (<5 METS), but not an
      abnormal MPI, can be associated with cardiac events at 3-year FU in asymptomatic
      type 2 diabetic patients.

PMID- 25380533
TI  - Structure of L-serine dehydratase from Legionella pneumophila: novel use of the C
      terminal cysteine as an intrinsic competitive inhibitor.
AB  - Here we report the first complete structure of a bacterial Fe-S l-serine
      dehydratase determined to 2.25 A resolution. The structure is of the type 2 l
      serine dehydratase from Legionella pneumophila that consists of a single
      polypeptide chain containing a catalytic alpha domain and a beta domain that is
      structurally homologous to the "allosteric substrate binding" or ASB domain of d
      3-phosphoglycerate dehydrogenase from Mycobacterium tuberculosis. The enzyme
      exists as a dimer of identical subunits, with each subunit exhibiting a bilobal
      architecture. The [4Fe-4S](2+) cluster is bound by residues from the C-terminal
      alpha domain and is situated between this domain and the N-terminal beta domain.
      Remarkably, the model reveals that the C-terminal cysteine residue (Cys 458),
      which is conserved among the type 2 l-serine dehydratases, functions as a fourth
      ligand to the iron-sulfur cluster producing a "tail in mouth" configuration. The
      interaction of the sulfhydryl group of Cys 458 with the fourth iron of the
      cluster appears to mimic the position that the substrate would adopt prior to
      catalysis. A number of highly conserved or invariant residues found in the beta
      domain are clustered around the iron-sulfur center. Ser 16, Ser 17, Ser 18, and
      Thr 290 form hydrogen bonds with the carboxylate group of Cys 458 and the
      carbonyl oxygen of Glu 457, whereas His 19 and His 61 are poised to potentially
      act as the catalytic base required for proton extraction. Mutation of His 61
      produces an inactive enzyme, whereas the H19A protein variant retains substantial
      activity, suggesting that His 61 serves as the catalytic base. His 124 and Asn
      126, found in an HXN sequence, point toward the Fe-S cluster. Mutational studies
      are consistent with these residues either binding a serine molecule that serves
      as an activator or functioning as a potential trap for Cys 458 as it moves out of
      the active site prior to catalysis. 

PMID- 25380530
TI  - Childhood and adolescent obesity and long-term cognitive consequences during
      aging.
AB  - The prevalence of childhood/adolescent obesity and insulin resistance has reached
      an epidemic level. Obesity's immediate clinical impacts have been extensively
      studied; however, current clinical evidence underscores the long-term
      implications. The current study explored the impacts of brief
      childhood/adolescent obesity and insulin resistance on cognitive function in
      later life. To mimic childhood/adolescent obesity and insulin resistance, we
      exposed 9-week-old C57BL/6J mice to a high-fat diet for 15 weeks, after which the
      mice exhibited diet-induced obesity and insulin resistance. We then put these
      mice back on a normal low-fat diet, after which the mice exhibited normal body
      weight and glucose tolerance. However, a spatial memory test in the forms of the
      Morris water maze (MWM) and contextual fear conditioning at 85 weeks of age
      showed that these mice had severe deficits in learning and long-term memory
      consolidation. Mechanistic investigations identified increased expression of
      histone deacetylases 5, accompanied by reduced expression of brain-derived
      neurotrophic factor, in the brains 61 weeks after the mice had been off the high
      fat diet. Electrophysiology studies showed that hippocampal slices isolated from
      these mice are more susceptible to synaptic impairments compared with slices
      isolated from the control mice. We demonstrated that a 15-week occurrence of
      obesity and insulin resistance during childhood/adolescence induces irreversible
      epigenetic modifications in the brain that persist following restoration of
      normal metabolic homeostasis, leading to brain synaptic dysfunction during aging.
      Our study provides experimental evidence that limited early-life exposure to
      obesity and insulin resistance may have long-term deleterious consequences in the
      brain, contributing to the onset/progression of cognitive dysfunction during
      aging.

PMID- 25380534
TI  - Dunaliella salina exhibits an antileukemic immunity in a mouse model of WEHI-3
      leukemia cells.
AB  - Dunaliella salina has been shown to have antioxidant property and induce
      apoptotic cell death of human cancer cells in vitro. However, there is no
      information available on D. salina showing an antileukemia effect or
      immunomodulatory activity in vivo. This study applied D. salina to syngeneic
      leukemia-implanted mice (BALB/c and WEHI-3) to investigate its immunological and
      antileukemia properties. Oral administration of D. salina (184.5, 369, and 922.5
      mg/kg) inhibited spleen metastasis and prolonged the survival in BALB/c mice that
      had received an intravenous injection of WEHI-3 cells. The results revealed that
      D. salina had reduced spleen enlargement in murine leukemia. It had also
      increased the population and proliferation of T-cells (CD3) and B-cells (CD19)
      following Con A/LPS treatment on flow cytometry and MTT assay, respectively.
      Furthermore, D. salina increased the phagocytosis of macrophages and enhanced the
      cytotoxicity of natural killer cells on flow cytometry and LDH assay. Moreover,
      D. salina enhanced the levels of interferon-gamma and interleukin 2 (IL-2) but
      reduced the levels of IL-4 and IL-10 in leukemic mice. In conclusion, these
      results demonstrated that the application of D. salina had beneficial effects on
      WEHI-3 leukemic mice by prolonging survival via modulating the immune responses. 

PMID- 25380535
TI  - The case for cost-effectively treating cryoglobulinemic vasculitis with
      interferon-free anti-hepatitis C virus therapy.

PMID- 25380536
TI  - Influence of depression symptoms on patient expectations and clinical outcomes in
      the surgical management of spinal stenosis.
AB  - OBJECT: This prospective cohort study was designed to determine the influence of
      depressive symptoms on patient expectations and the clinical outcomes of the
      surgical management of lumbar spinal stenosis. METHODS: Patients with an age > 45
      years, a diagnosis of lumbar spinal stenosis at one level, and an indication for
      decompressive surgery were included in this study. Data for all of the following
      parameters were recorded: age, sex, highest level of education, and employment
      status. Depression symptoms (Beck Depression Inventory), disability (Oswestry
      Disability Index), and back and leg pain (visual analog scale) were assessed
      before surgery and at 12 months thereafter. The reasons for surgery and patient
      expectations (North American Spine Society lumbar spine questionnaire) were noted
      before surgery. The global effectiveness of surgery (Likert scale) was assessed
      at the 1-year follow-up. RESULTS: Fifty-eight patients were divided into two
      groups based on the presence (Group 1) or absence (Group 2) of depressive
      symptoms preoperatively; each group comprised 29 patients. Demographic data were
      similar in both groups before surgery. The main reason to undergo surgery was
      "fear of a worse situation" in 34% of the patients in Group 1 and "to reduce
      pain" in 24% of the patients in Group 2. The most prevalent expectation was to
      improve my social life and my mental health in both groups. Surgery had a
      relieving effect on the depressive symptoms in 14 patients (48%). Thus, in the
      postoperative period, the number of patients who were free of depressive symptoms
      was 43 compared with the 15 who were depressed (p = 0.001). The 15 patients with
      persistent depression symptoms after surgery had a worse clinical outcome
      compared with the 43 patients free of depression symptoms at the 1-year follow-up
      in terms of severe back pain (20% vs. 0%, respectively), severe leg pain (40% vs.
      2.3%, respectively), and severe disability (53% vs. 9.3%, respectively). Only 33%
      of patients with persistent depression symptoms after surgery chose the option
      "surgery helped a lot" compared with 76% of patients without depression symptoms.
      Moreover, in terms of expectations regarding improvement in back pain, leg pain,
      walking capacity, independence, physical duties, and social activities, fewer
      patients were "completely satisfied" in the group with persistent depression
      symptoms after surgery. CONCLUSIONS: Surgery for spinal stenosis had a relieving
      effect on preoperative depression symptoms at the 1-year follow-up. The
      persistence of depressive symptoms after surgery correlated with a worse clinical
      outcome and a higher rate of unmet expectations. Screening measures to detect and
      treat depression symptoms in the perioperative period could lead to better
      clinical results and increased patient satisfaction.

PMID- 25380537
TI  - Evaluation of monoenergetic imaging to reduce metallic instrumentation artifacts
      in computed tomography of the cervical spine.
AB  - OBJECT: Monoenergetic imaging with dual-energy CT has been proposed to reduce
      metallic artifacts in comparison with conventional polychromatic CT. The purpose
      of this study is to systematically evaluate and define the optimal dual-energy CT
      imaging parameters for specific cervical spinal implant alloy compositions.
      METHODS: Spinal fixation rods of cobalt-chromium or titanium alloy inserted into
      the cervical spine section of an Alderson Rando anthropomorphic phantom were
      imaged ex vivo with fast-kilovoltage switching CT at 80 and 140 peak kV. The
      collimation width and field of view were varied between 20 and 40 mm and medium
      to large, respectively. Extrapolated monoenergetic images were generated at 70,
      90, 110, and 130 kiloelectron volts (keV). The standard deviation of voxel
      intensities along a circular line profile around the spine was used as an index
      of the magnitude of metallic artifact. RESULTS: The metallic artifact was more
      conspicuous around the fixation rods made of cobalt-chromium than those of
      titanium alloy. The magnitude of metallic artifact seen with titanium fixation
      rods was minimized at monoenergies of 90 keV and higher, using a collimation
      width of 20 mm and large field of view. The magnitude of metallic artifact with
      cobalt-chromium fixation rods was minimized at monoenergies of 110 keV and
      higher; collimation width or field of view had no effect. CONCLUSIONS:
      Optimization of acquisition settings used with monoenergetic CT studies might
      yield reduced metallic artifacts.

PMID- 25380538
TI  - Two-level total disc replacement with Mobi-C cervical artificial disc versus
      anterior discectomy and fusion: a prospective, randomized, controlled multicenter
      clinical trial with 4-year follow-up results.
AB  - OBJECT: The purpose of this study was to evaluate the safety and effectiveness of
      2-level total disc replacement (TDR) using a Mobi-C cervical artificial disc at
      48 months' follow-up. METHODS: A prospective randomized, US FDA investigational
      device exemption pivotal trial of the Mobi-C cervical artificial disc was
      conducted at 24 centers in the U.S. Three hundred thirty patients with
      degenerative disc disease were randomized and treated with cervical total disc
      replacement (225 patients) or the control treatment, anterior cervical discectomy
      and fusion (ACDF) (105 patients). Patients were followed up at regular intervals
      for 4 years after surgery. RESULTS: At 48 months, both groups demonstrated
      improvement in clinical outcome measures and a comparable safety profile. Data
      were available for 202 TDR patients and 89 ACDF patients in calculation of the
      primary endpoint. TDR patients had statistically significantly greater
      improvement than ACDF patients for the following outcome measures compared with
      baseline: Neck Disability Index scores, 12-Item Short Form Health Survey Physical
      Component Summary scores, patient satisfaction, and overall success. ACDF
      patients experienced higher subsequent surgery rates and displayed a higher rate
      of adjacent-segment degeneration as seen on radiographs. Overall, TDR patients
      maintained segmental range of motion through 48 months with no device failure.
      CONCLUSIONS: Four-year results from this study continue to support TDR as a safe,
      effective, and statistically superior alternative to ACDF for the treatment of
      degenerative disc disease at 2 contiguous cervical levels. Clinical trial
      registration no.: NCT00389597 ( clinicaltrials.gov ).

PMID- 25380539
TI  - Experience with intrawound vancomycin powder for posterior cervical fusion
      surgery.
AB  - OBJECT: Recent studies have reported that the local delivery of vancomycin powder
      is associated with a decrease in spinal surgical site infection. This
      retrospective cohort study compares posterior cervical fusion cases before and
      after the routine application of spinal vancomycin powder to evaluate the ability
      of local vancomycin powder to prevent deep wound infection after posterior
      cervical spinal fusion. METHODS: Posterior cervical fusion spinal surgeries
      performed at a single institution were reviewed from January 2011 to July 2013.
      Each cohort's baseline characteristics, operative data, and rates of wound
      infection were compared. Associations between infection and vancomycin powder,
      with and without propensity score adjustment for risk factors, were determined
      using logistic regression. RESULTS: A total of 289 patients (174 untreated and
      115 treated with vancomycin powder) were included in the study. The cohorts were
      similar in terms of baseline and operative variables. No significant change in
      deep wound infection rate was seen between the control group (6.9%) and
      intervention group (5.2%, p = 0.563). Logistic regression, with and without
      propensity score adjustment, demonstrated that the use of vancomycin powder did
      not impact the development of surgical site infection (OR 0.743 [95% CI 0.270
      2.04], p = 0.564) and (OR 0.583 [95% CI 0.198-1.718], p = 0.328), respectively.
      CONCLUSIONS: Within the context of an ongoing debate on the effectiveness of
      locally administered vancomycin powder, the authors found no significant
      difference in the incidence of deep wound infection rates after posterior
      cervical fusion surgery with routine use of locally applied vancomycin powder.
      Future prospective randomized series are needed to corroborate these results.

PMID- 25380540
TI  - A modified Bohlman technique using a novel implant for treatment of high-grade
      spondylolisthesis.
AB  - Several surgical options for managing high-grade spondylolisthesis have been
      described in the literature and range from posterior-only in situ fusion to
      circumferential fusion with complete reduction of the dislocation. The level of
      evidence supporting any one technique is weak, and to date there is no Level I or
      II evidence supporting any current surgical treatment option. Techniques have
      evolved as implant technology has advanced and surgeons have gained experience
      with deformity correction. Still, the paucity of cases at any one institution
      limits the ability to perform clinical studies in a prospective and randomized
      fashion. To the authors' knowledge, the use of the AxiaLif bolt in a modified
      Bohlman technique has not been described. In the setting of a case of symptomatic
      high-grade spondylolisthesis refractory to nonoperative management, the authors
      describe a modified Bohlman technique in which they used the AxiaLif bolt rather
      than the fibula graft that was originally described. They then supplemented this
      with pedicle screw instrumentation and an iliac crest autograft. At the 2-year
      follow-up exam, the patient exhibited relief of his preoperative back and leg
      pain and he had returned to all activities. The latest radiographs demonstrated
      successful fusion. A single-stage, posterior instrumented fusion in which the
      AxiaLif bolt is used in lieu of fibula autograft or allograft in a modified
      Bohlman technique is technically less demanding, does not have the morbidity
      associated with harvesting a fibula autograft, and carries no risk of disease
      transmission associated with the use of allograft. 

PMID- 25380541
TI  - Spinal stimulator peri-electrode masses: case report.
AB  - The authors describe a case of delayed spastic quadriparesis caused by a peri
      electrode mass following the implantation of a minimally invasive percutaneous
      spinal cord stimulator (SCS). Prior reports with paddle-type electrodes are
      reviewed, and a detailed histological and pathophysiological comparison with the
      present case is made. The patient developed tolerance to a cervical percutaneous
      SCS 4 months after implantation, followed by the onset of spastic quadriparesis 9
      months after implantation. The stimulator was removed, and contrast-enhanced MRI
      revealed an enhancing epidural mass where the system had been placed, with severe
      spinal cord compression. Decompression was carried out, and the patient
      experienced neurological improvement. Pathological examination revealed fibrotic
      tissue with granulomatous and multinucleated giant cell reactions. No evidence of
      infection or hemorrhage was found. Professionals treating patients with SCSs or
      contemplating their insertion should be aware of this delayed complication and
      associated risk factors. 

PMID- 25380542
TI  - In vitro enzymic hydrolysis of chlorogenic acids in coffee.
AB  - SCOPE: Coffee is rich in quinic acid esters of phenolic acids (chlorogenic acids)
      but also contains some free phenolic acids. A proportion of phenolic acids appear
      in the blood rapidly after coffee consumption due to absorption in the small
      intestine. We investigated in vitro whether this appearance could potentially be
      derived from free phenolic acids in instant coffee or from hydrolysis of
      chlorogenic acids by pancreatic or brush border enzymes. METHODS AND RESULTS: We
      quantified six free phenolic acids in instant coffees using HPLC-DAD-mass
      spectrometry. The highest was caffeic acid, but all were present at low levels
      compared to the chlorogenic acids. Roasting and decaffeination significantly
      reduced free phenolic acid content. We estimated, using pharmacokinetic modelling
      with previously published data, that the contribution of these compounds to small
      intestinal absorption is minimal. Hydrolysis of certain chlorogenic acids was
      observed with human-differentiated Caco-2 cell monolayers and with porcine
      pancreatin, which showed maximal rates on 3- and 5-O-caffeoylquinic acids,
      respectively. CONCLUSION: The amounts of certain free phenolic acids in coffee
      could only minimally account for small intestinal absorption based on modelling.
      The hydrolysis of caffeoylquinic, but not feruloylquinic acids, by enterocyte and
      pancreatic esterases is potentially a contributing mechanism to small intestinal
      absorption.

PMID- 25380543
TI  - Electrocatalytic H2 production from seawater over Co, N-codoped nanocarbons.
AB  - One of the main barriers blocking sustainable hydrogen production is the use of
      expensive platinum-based catalysts to produce hydrogen from water. Herein we
      report the cost-effective synthesis of catalytically active, nitrogen-doped,
      cobalt-encased carbon nanotubes using inexpensive starting materials-urea and
      cobalt chloride hexahydrate (CoCl2.6H2O). Moreover, we show that the as-obtained
      nanocarbon material exhibits a remarkable electrocatalytic activity toward the
      hydrogen evolution reaction (HER); and thus it can be deemed as a potential
      alternative to noble metal HER catalysts. In particular, the urea-derived carbon
      nanotubes synthesized at 900  degrees C (denoted as U-CNT-900) show a superior
      catalytic activity for HER with low overpotential and high current density in our
      study. Notably also, U-CNT-900 has the ability to operate stably at all pH values
      (pH 0-14), and even in buffered seawater (pH 7). The possible synergistic effects
      between carbon-coated cobalt nanoparticles and the nitrogen dopants can be
      proposed to account for the HER catalytic activity of U-CNT-900. Given the high
      natural abundance, ease of synthesis, and high catalytic activity and durability
      in seawater, this U-CNT-900 material is promising for hydrogen production from
      water in industrial applications. 

PMID- 25380544
TI  - Late-stage diversification of biologically active pyridazinones via a direct C-H
      functionalization strategy.
AB  - Divergent C-H functionalization reactions (arylation, carboxylation, olefination,
      thiolation, acetoxylation, halogenation, naphthylation) using a pyridazinone
      moiety as an internal directing group were successfully established. This
      approach offers a late-stage, ortho-selective diversification of a biologically
      active pyridazinone scaffold. Seven series of novel pyridazinone analogues were
      synthesized conveniently as the synthetic precursors of potential sortase A
      (SrtA) inhibitors. 

PMID- 25380545
TI  - Heterogeneous carbon gels: N-doped carbon xerogels from resorcinol and N
      containing heterocyclic aldehydes.
AB  - Direct, acid (HCl) initiated sol-gel polycondensation of resorcinol with pyrrole
      2-carboxaldehyde or its derivative N-methyl-2-pyrrolecarboxaldehyde yields
      thermosetting phenolic organic gels with N-content of up to 8.4 wt %. After
      carbonization, sturdy monoliths of N-doped carbon xerogels with N-content of up
      to 8 wt % are produced. The morphology and porosity of the doped carbons can be
      tuned by the solvent composition and the amount of polymerization catalyst used.
      An increase in carbonization temperature from 600 to 1000  degrees C strongly
      affects the carbon gels' microporosity, resulting in a decrease in N2 adsorption
      capacity, but a significant increase in H2 adsorption capacity (at -196  degrees
      C). The growing H2 sorption capacity with the decreasing specific surface area
      (measured by N2) is related to the gradual shrinkage of the carbon xerogel matrix
      and narrowing of the small micropores. In addition, it is demonstrated that
      pyridine-based heterocyclic aldehydes, that is, 2- or 4-pyridinecarboxaldehyde,
      condensate with resorcinol in basic conditions (KOH, NH4OH). However, in this
      case, monoliths cannot be produced and powders/rigid solid precipitates are
      obtained instead. If NH4OH is used as a sol-gel polycondensation catalyst, N
      doped foams are obtained as a final carbonaceous product. 

PMID- 25380546
TI  - Insight into deactivation of commercial SCR catalyst by arsenic: an experiment
      and DFT study.
AB  - Fresh and arsenic-poisoned V2O5-WO3/TiO2 catalysts are investigated by
      experiments and DFT calculations for SCR activity and the deactivation mechanism.
      Poisoned catalyst (1.40% of arsenic) presents lower NO conversion and more N2O
      formation than fresh. Stream (5%) could further decrease the activity of poisoned
      catalyst above 350  degrees C. The deactivation is not attributed to the loss of
      surface area or phase transformation of TiO2 at a certain arsenic content, but
      due to the coverage of the V2O5 cluster and the decrease in the surface acidity:
      the number of Lewis acid sites and the stability of Bronsted acid sites. Large
      amounts of surface hydroxyl induced by H2O molecules provide more unreactive As
      OH groups and give rise to a further decrease in the SCR activity. N2O is mainly
      from NH3 unselective oxidation at high temperatures since the reducibility of
      catalysts and the number of surface-active oxygens are improved by As2O5.
      Finally, the reaction pathway seems unchanged after poisoning: NH3 adsorbed on
      both Lewis and Bronsted acid sites is reactive.

PMID- 25380547
TI  - How inhibiting nitrification affects nitrogen cycle and reduces environmental
      impacts of anthropogenic nitrogen input.
AB  - Anthropogenic activities, and in particular the use of synthetic nitrogen (N)
      fertilizer, have doubled global annual reactive N inputs in the past 50-100
      years, causing deleterious effects on the environment through increased N
      leaching and nitrous oxide (N2 O) and ammonia (NH3 ) emissions. Leaching and
      gaseous losses of N are greatly controlled by the net rate of microbial
      nitrification. Extensive experiments have been conducted to develop ways to
      inhibit this process through use of nitrification inhibitors (NI) in combination
      with fertilizers. Yet, no study has comprehensively assessed how inhibiting
      nitrification affects both hydrologic and gaseous losses of N and plant nitrogen
      use efficiency. We synthesized the results of 62 NI field studies and evaluated
      how NI application altered N cycle and ecosystem services in N-enriched systems.
      Our results showed that inhibiting nitrification by NI application increased NH3
      emission (mean: 20%, 95% confidential interval: 33-67%), but reduced dissolved
      inorganic N leaching (-48%, -56% to -38%), N2 O emission (-44%, -48% to -39%) and
      NO emission (-24%, -38% to -8%). This amounted to a net reduction of 16.5% in the
      total N release to the environment. Inhibiting nitrification also increased plant
      N recovery (58%, 34-93%) and productivity of grain (9%, 6-13%), straw (15%, 12
      18%), vegetable (5%, 0-10%) and pasture hay (14%, 8-20%). The cost and benefit
      analysis showed that the economic benefit of reducing N's environmental impacts
      offsets the cost of NI application. Applying NI along with N fertilizer could
      bring additional revenues of $163 ha(-1)  yr(-1) for a maize farm, equivalent to
      8.95% increase in revenues. Our findings showed that NIs could create a win-win
      scenario that reduces the negative impact of N leaching and greenhouse gas
      production, while increases the agricultural output. However, NI's potential
      negative impacts, such as increase in NH3 emission and the risk of NI
      contamination, should be fully considered before large-scale application. 

PMID- 25380548
TI  - Precipitates of Al(III), Sc(III), and La(III) at the muscovite-water interface.
AB  - The interaction of Al(III), Sc(III), and La(III) with muscovite-water interfaces
      was studied at pH 4 and 10 mM NaCl using second harmonic generation (SHG) and X
      ray photoelectron spectroscopy (XPS). SHG data for Sc(III) and La(III) suggest
      complete and/or partial irreversible adsorption that is attributed by XPS to the
      growth of Sc(III) and La(III) hydroxides/oxides on the muscovite surface. Al(III)
      adsorption appears to coincide with the growth of gibbsite (Al(OH)3) deposits on
      the muscovite surface, as indicated by the magnitude of the interfacial potential
      computed from the SHG data. This interpretation of the data is consistent with
      previous studies reporting the epitaxial growth of gibbsite on the muscovite
      surface under similar conditions. The implication of our findings is that the
      surface charge density of mica may change (and in the case of Al(III), even flip
      sign from negative (mica) to positive (gibbsite)) when Al(III), Sc(III), or
      La(III) is present in aqueous phases in contact with heterogeneous geochemical
      media rich in mica-class minerals, even at subsaturation conditions. 

PMID- 25380549
TI  - Could red cell distribution width be a marker in Hashimoto's thyroiditis?
AB  - AIMS: Hashimoto's Thyroiditis (HT) is the most common autoimmune thyroiditis
      worldwide and characterized with lymphomonocytic inflammation of the thyroid
      gland. Red cell distribution width (RDW) reflects erythrocyte anisocytosis and
      besides it increases in iron deficiency anemia, recent studies reported that RDW
      was also associated with conditions characterized with overt or subclinical
      inflammation. We aimed to answer whether RDW increased in Hashimoto's
      thyroiditis. METHODS: Patients with HT admitted to outpatient clinic of our
      hospital were included to the study. Patients with anemia (especially iron
      deficiency), diabetes mellitus, chronic inflammatory disease and on medication
      that may affect hemogram results (e. g., aspirin) excluded from the study.
      Patient characteristics, thyroid stimulating hormone (TSH), Free T3 (FT3), Free
      T4 (FT4), Anti-thyroid peroxidase (Anti-TPO), Anti-Thyroglobulin (Anti-TG),
      leukocyte count (WBC), Hemoglobin (Hb), Hematocrit (Htc), mean corpuscular volume
      (MCV), RDW and platelet count (PLT) values of the study cohort were obtained from
      computerized database of our institution. RESULTS: There was no significant
      difference between study and control groups in terms of WBC, Hb, Htc, MCV, PLT,
      PDW and FT3 levels. However, FT4 level was significantly lower and TSH was
      significantly higher in study group compared to controls. RDW was significantly
      increased in study group compared to control group. CONCLUSION: We suggest that
      elevated RDW values in patients without iron deficiency anemia may require
      further evaluation for HT, especially in female population.

PMID- 25380550
TI  - Relationship between the level of hippocampal leptin receptor gene expression and
      learning performance in diabetic rats.
AB  - Diabetes mellitus may be associated with impaired cognitive function. Decreased
      peripheral glucose regulation was associated with decreased general cognitive
      performance, memory impairments, and atrophy of the hippocampus, a brain area
      that is key for learning and memory. Leptin that is a peptide hormone, acts in
      the hippocampus where it facilitates the induction of long-term potentiation and
      enhances NMDA receptor mediated transmission. The aim of the present study is to
      investigate possible relationship between the hippocampal leptin receptor gene
      expression and learning performance in streptozotocin (STZ) induced diabetic
      rats. In this study was conducted on a total of 40 Winstar albino female rats,
      including a control group consisting of 20 rats and experimental group comprising
      of 20 rats in which diabetes was induced by means of STZ administration. Leptin
      receptor gene expression was detected in hippocampal samples by using real time
      PCR. According to the evaluation, the learning performance of rats with induced
      diabetes was found to be same throughout the first 3 days after STZ in comparison
      to the control group rats. End of the 45 days the learning performance of the
      control group was found to be better than the diabetic group (p<0.05). Hipocampal
      leptin receptor expression was found lower in diabetic group than the control
      group (p<0.05). The results provide evidence that leptin receptor gene may
      related to learning performance in diabetic rats. Further, detailed studies are
      needed to address the exact role of leptin and related molecules in learning
      performance. 

PMID- 25380551
TI  - Analysis of expressed sequence tags (ESTs) from a normalized cDNA library and
      isolation of EST simple sequence repeats from the invasive cotton mealybug
      Phenacoccus solenopsis.
AB  - The cotton mealybug, Phenacoccus solenopsis Tinsley, is a serious and invasive
      pest. At present, genetic resources for studying P. solenopsis are limited, and
      this negatively affects genetic research on the organism and, consequently,
      translational work to improve management of this pest. In the present study,
      expressed sequence tags (ESTs) were analyzed from a normalized complementary DNA
      library of P. solenopsis. In addition, EST-derived microsatellite loci (also
      known as simple sequence repeats or SSRs) were isolated and characterized. A
      total of 1107 high-quality ESTs were acquired from the library. Clustering and
      assembly analysis resulted in 785 unigenes, which were classified functionally
      into 23 categories according to the Gene Ontology database. Seven EST-based SSR
      markers were developed in this study and are expected to be useful in
      characterizing how this invasive species was introduced, as well as providing
      insights into its genetic microevolution. 

PMID- 25380552
TI  - Should patients with hepatitis C genotype 2/3 infection who are slow responders
      to pegylated interferon/ribavirin have treatment duration extended?

PMID- 25380553
TI  - Take the bite out of food allergies.

PMID- 25380555
TI  - One-step transepithelial photorefractive keratectomy with mitomycin C as an early
      treatment for LASIK flap buttonhole formation.
AB  - PURPOSE: To assess the efficacy and safety of early one-step transepithelial
      photorefractive keratectomy (PRK) with mitomycin C as treatment for buttonhole
      formation during LASIK. METHODS: Eight patients who developed a buttonhole during
      LASIK with mechanical or femtosecond flap creation underwent one-step
      transepithelial PRK a few days after the formation of the buttonhole. The re
      treatment procedure was performed after complete epithelial healing and smooth
      epithelial fluorescein profile were ensured. Postoperative manifest refraction,
      uncorrected and corrected distance visual acuity, and haze formation were
      assessed during 6 months of follow-up. RESULTS: Mean duration of the re-treatment
      procedure after buttonhole formation was 5 days (range: 4 to 7 days). Mean
      manifest refractive spherical equivalent and cylinder refraction were -0.05 +/-
      0.18 and -0.18 +/- 0.22 diopters, respectively, at 6 months postoperatively.
      Uncorrected distance visual acuity was 20/20 in all patients after 3 months of
      follow-up. No haze formation was detected. CONCLUSIONS: Early one-step
      transepithelial PRK with mitomycin C seems to be a safe and effective treatment
      for LASIK buttonhole complication.

PMID- 25380556
TI  - Exploring factors associated with sexual activity in community-dwelling older
      adults.
AB  - Sexuality is an important, yet often overlooked, aspect of successful aging. The
      current article explores potential relationships between sexual activity in older
      adults and marital status, health, mobility, urinary incontinence, and caffeine
      and alcohol use, as well as sexual desire and erectile function in women and men,
      respectively. A survey was mailed to community-dwelling older adults 60 and
      older. Of 242 respondents (79% ages 60 to 74, 53% male), 159 (65.7%) were
      sexually active. A higher proportion of sexually active adults were married (p =
      0.0005), had better health (p = 0.0003), and drank alcohol (p = 0.007). A lower
      proportion of sexually active adults had urinary incontinence (p = 0.006).
      Similar proportions of men and women were sexually active (62.8% and 68.2%,
      respectively; p = 0.38). Sexually active women had better sexual desire scores (p
      < 0.0001) and more drank alcohol (p = 0.0013). Sexually active men had better
      mobility (p = 0.012) and erectile function (p < 0.0001). Fewer sexually active
      men had incontinence (p < 0.0001). Only alcohol use and no urinary incontinence
      were predictors unique to women and men, respectively. Health care providers must
      be aware of factors that may impact sexual health in older adults.

PMID- 25380557
TI  - High-yield, ultrafast, surface plasmon-enhanced, Au nanorod optical field
      electron emitter arrays.
AB  - Here we demonstrate the design, fabrication, and characterization of ultrafast,
      surface-plasmon enhanced Au nanorod optical field emitter arrays. We present a
      quantitative study of electron emission from Au nanorod arrays fabricated by high
      resolution electron-beam lithography and excited by 35 fs pulses of 800 nm light.
      We present accurate models for both the optical field enhancement of Au nanorods
      within high-density arrays, and electron emission from those nanorods. We have
      also studied the effects of surface plasmon damping induced by metallic interface
      layers at the substrate/nanorod interface on near-field enhancement and electron
      emission. We have identified the peak optical field at which the electron
      emission mechanism transitions from a 3-photon absorption mechanism to strong
      field tunneling emission. Moreover, we have investigated the effects of nanorod
      array density on nanorod charge yield, including measurement of space-charge
      effects. The Au nanorod photocathodes presented in this work display 100-1000
      times higher conversion efficiency relative to previously reported UV triggered
      emission from planar Au photocathodes. Consequently, the Au nanorod arrays
      triggered by ultrafast pulses of 800 nm light in this work may outperform
      equivalent UV-triggered Au photocathodes, while also offering nanostructuring of
      the electron pulse produced from such a cathode, which is of interest for X-ray
      free-electron laser (XFEL) development where nanostructured electron pulses may
      facilitate more efficient and brighter XFEL radiation. 

PMID- 25380558
TI  - Clinic and electromyographic results of latissimus dorsi transfer for irreparable
      posterosuperior rotator cuff tears.
AB  - BACKGROUND: This study examines the clinical and electromyographic results of
      latissimus dorsi transfer (LDT) using a combined open and arthroscopic technique
      for the treatment of symptomatic irreparable posterosuperior rotator cuff tears.
      METHODS: Between 2006 and 2009, LDT was performed in 14 patients (mean age 59
      years) with massive and symptomatic irreparable posterosuperior rotator cuff
      tear. The patients were examined preoperatively and postoperatively with mean
      follow-up of 52 months using the Constant score, and the integrity of the
      latissimus dorsi (LD) transfer was assessed by ultrasound in all cases and by MRI
      in ten cases. The functional activity of the LD transfer was compared to the non
      operated side using surface electromyography. RESULTS: All patients demonstrated
      a significant improvement in the Constant score (p = 0.001), from a preoperative
      score of 33 points (range 10-55 points) to a postoperative score of 59 points
      (range 13-80 points). The subjective assessment score was good to excellent in 12
      patients (85%), and 11 patients (78%) would be willing to undergo surgery again.
      Integrity of the transferred tissue was confirmed in 13 of the 14 cases using
      ultrasound and MRI. Surface electromyographic signal showed increased activation
      of the transferred latissimus dorsi when performing active movements of external
      rotation (p = 0.002) and abduction-elevation (p = 0.009). CONCLUSIONS: Our
      results indicate that LDT significantly improves function and diminishes pain in
      patients with a massive posterosuperior rotator cuff tear. The combined open and
      arthroscopic technique preserves the deltoid muscle and controls the LD tendon
      reinsertion. Surface electromyographic signal confirms the active function of the
      transferred muscle.

PMID- 25380559
TI  - Flow sensing in developing Xenopus laevis is disrupted by visual cues and
      ototoxin exposure.
AB  - We explored how lateral line cues interact with visual cues to mediate flow
      sensing behaviors in the nocturnal developing frog, Xenopus laevis, by exposing
      animals to current flows under different lighting conditions and after exposure
      to the ototoxin gentamicin. Under dark conditions, Xenopus tadpoles move
      downstream at the onset of current flow, then turn, and orient toward the
      direction of the flow with high accuracy. Postmetamorphic froglets also exhibit
      positive rheotaxis but with less accuracy and longer latency. The addition of
      discrete light cues to an otherwise dark environment disrupts rheotaxis and
      positioning. Orientation is less accurate, latency to orient is longer, and
      animals do not move as far downstream in the presence of light. Compared with
      untreated tadpoles tested in the dark, tadpoles exposed to gentamicin show less
      accurate rheotaxis with longer latency and do not move as far downstream in
      response to flow. These effects are compounded by the presence of light cues. The
      disruptive effects of light on flow sensing in Xenopus emphasize the disturbances
      to natural behaviors that may be produced by anthropogenic illumination in
      nocturnal habitats. 

PMID- 25380561
TI  - The management of sportsman's groin hernia in professional and amateur soccer
      players: a revised concept.
AB  - BACKGROUND: Chronic groin pain appears in athletes with a diverse etiology. In a
      select few, it can be defined as a sportsman's hernia, that may be related, among
      other pathologies, to weakness of the posterior inguinal wall and may
      successfully respond to surgery. HYPOTHESIS: Surgical repair of the sportsman's
      hernia is associated with good functional outcomes, if the diagnosis is based on
      meticulous examination and follows a simple selection flowchart. STUDY DESIGN:
      Prospective case cohort study. METHODS: The study assessed patients recruited
      from 2006 until the present assessed by a dedicated team with clinical and
      radiographic features of a sportsman's hernia who had failed a specified period
      of conservative therapies. Surgery was performed using a tension-free mesh open
      inguinal hernia repair. RESULTS: Of 246 male patients with chronic groin pain, 51
      underwent surgery (mean age 20.7 years, range 14-36 years) with 58 inguinal
      procedures performed. Of the operated group, seven underwent bilateral surgery
      with a direct hernia found in 9/58 operated sides (15.5%), an indirect hernial
      sac in 8/58 (14%) and a direct and indirect hernia being found in 3/58 (5%) of
      operated sides. There was no post-operative morbidity (median follow-up 36.1
      months; range 1-74 months), with two failures (3.45 % of operated sides). All
      other patients were asymptomatic, returned to full sports activity within 4.3
      weeks (range 3-8 weeks) after surgery, and required no analgesics or further
      treatment. CONCLUSION: Selective surgical hernia repair, based on meticulous
      anamnesis and physical examination is effective in the management of chronic
      groin pain in athletes.

PMID- 25380560
TI  - A systematic review of the surgical treatment of large incisional hernia.
AB  - PURPOSE: Incisional hernia (IH) is one of the most frequent postoperative
      complications. Of all patients undergoing IH repair, a vast amount have a hernia
      which can be defined as a large incisional hernia (LIH). The aim of this study is
      to identify the preferred technique for LIH repair. METHODS: A systematic review
      of the literature was performed and studies describing patients with IH with a
      diameter of 10 cm or a surface of 100 cm2 or more were included. Recurrence
      hazards per year were calculated for all techniques using a generalized linear
      model. RESULTS: Fifty-five articles were included, containing 3,945 LIH repairs.
      Mesh reinforced techniques displayed better recurrence rates and hazards than
      techniques without mesh reinforcement. Of all the mesh techniques, sublay repair,
      sandwich technique with sublay mesh and aponeuroplasty with intraperitoneal mesh
      displayed the best results (recurrence rates of <3.6%, recurrence hazard <0.5%
      per year). Wound complications were frequent and most often seen after complex
      LIH repair. CONCLUSIONS: The use of mesh during LIH repair displayed the best
      recurrence rates and hazards. If possible mesh in sublay position should be used
      in cases of LIH repair.

PMID- 25380562
TI  - A case report of retroperitoneal pararenal Castleman's disease associated with
      myasthenia gravis.
AB  - BACKGROUND: Castleman's disease (CD) is a relatively rare disorder characterized
      by the benign proliferation of lymphoid tissue. The combination of an occurrence
      of retroperitoneal pararenal CD with myasthenia gravis (MG) is extremely rare.
      CASE PRESENTATION: The patient was admitted to our hospital for investigation of
      a retroperitoneal pararenal tumor which had been coincidentally diagnosed at a
      local hospital where he was admitted because of MG. The patient subsequently
      underwent an exploratory laparotomy and suffered from postoperative myasthenic
      crisis. Pathological examination revealed a left retroperitoneal mass of CD
      (hyaline vascular type). There was no recurrence of disease found after 7 months.
      CONCLUSIONS: CD with MG is a rare condition. Postoperative myasthenic crisis is a
      severe complication. The possibility of its occurrence must be in physicians'
      minds and the risk of postoperative myasthenic crisis must be carefully
      considered when evaluating MG patients undergoing surgery.

PMID- 25380563
TI  - Changes in attitudes toward and patterns in traditional Korean medicine among the
      general population in South Korea: a comparison between 2008 and 2011.
AB  - BACKGROUND: Traditional Korean medicine (TKM) is acknowledged to be prevalent
      among the Korean public, but few follow-up studies are available to confirm this
      commonly held belief. Whereas most survey studies have focused on the demographic
      factors influencing the usage of TKM, only a few studies have conducted a pattern
      or trend analysis over time. The purpose of this paper is to observe and document
      recent trends in the usage of TKM in South Korea and to compare overall patterns
      of TKM use over a period of several years. METHODS: A cross-sectional survey was
      conducted in 2011 to assess TKM usage patterns and public perceptions regarding
      TKM. An online questionnaire was administered to consenting respondents that
      focused upon individual preferences between TKM and current Western medicine,
      respondents' reasons for using TKM, the frequency of respondents' visits to TKM
      clinics, the reasons respondents visited TKM clinics, and respondents' perceived
      satisfaction. RESULTS: The results revealed that 66.6% of the respondents showed
      a positive attitude toward TKM. In addition, 69.3% of the respondents had visited
      TKM clinics one to four times during the previous year. Patients used TKM with
      the intentions of receiving acupuncture (95.3%), moxibustion (40.1%), and cupping
      (36.0%) treatments or to take herbal medicines (35.7%). Most respondents who had
      visited TKM clinics were largely satisfied with the clinics' effectiveness
      (56.1%). The factors most commonly associated with TKM usage included sex
      (female), age (50s), and education (college or higher), but the within-factor
      differences were not significant. Compared with a previous survey of other
      groups, TKM usage was found to have increased from 45.8% in 2008 to 69.3% in
      2011. With the exception of acupuncture and physical therapy, most usage doubled
      or more than doubled. CONCLUSIONS: The attitudes toward and usage of TKM in South
      Korea have improved between 2008 and 2011. This result will be used to explain
      outcomes of certain social phenomena and to argue for national support in the
      promotion of TKM.

PMID- 25380564
TI  - [Physical training for neurological and mental diseases].
AB  - BACKGROUND: Physical activity has beneficial effects on somatic and mental health
      factors; therefore, regular exercise has preventive and therapeutic capabilities
      to improve neurological and mental dysfunction. OBJECTIVES: In this overview of
      the current literature, the evidence of the effects of exercise on such disorders
      is summarized. Physical exercise interventions for stroke, Parkinson's disease,
      dementia, depression, psychoses, anxiety disorders, and chronic pain syndromes
      are considered in detail. RESULTS: Physical activity reduces the risk of
      suffering from stroke, dementia and Parkinson's disease. Furthermore, it is
      negatively correlated with dysthymia and other depressive symptoms and various
      anxiety and pain disorders as well as headache syndromes. A therapeutic effect of
      systematic physical exercise was revealed for depression, some symptoms of
      psychosis and multiple sclerosis, addiction, eating disorders, the fibromyalgia
      syndrome as well as short-term interventions for anxiety disorders. CONCLUSION:
      The concerted integration of physical exercise into prophylactic and therapeutic
      interventions can lower the burden of neurological and mental diseases; however,
      scientific evidence is still lacking concerning the optimal duration, type, and
      intensity as well as potential risks of physical exercise.

PMID- 25380565
TI  - Epigenetic regulation of Tbx18 gene expression during endochondral bone
      formation.
AB  - Endochondral bone formation is tightly regulated by the spatial and sequential
      expression of a series of transcription factors. To disclose the roles of TBX18,
      a member of the T-box transcription factor family, during endochondral bone
      formation, its spatial and temporal expression patterns were characterized in the
      limb skeletal region of the developing mouse together with those of established
      osteochondrogenic markers Sox9, Col2a1, and Runx2. TBX18 expression first
      appeared in condensed mesenchymal cells (chondro-progenitors) in embryonic-day
      10.5 (E10.5) limb bud and was co-localized with Sox9 expression, whereas at E11.5
      and E12.5, it became undetectable in mesenchymal cells committed to the
      chondrocyte lineage. From E13.5 to E18.5, TBX18 expression reappeared in
      chondrocytes, correlating strongly with Col2a1 expression; furthermore, low level
      TBX18 expression was found in the Runx2-positive perichondral osteoblastic cell
      lineage. At the postnatal stage, TBX18 expression was observed in epiphyseal
      chondrocytes and osteocytes within the lacunae of mature trabecular bone. On the
      assumption that such characteristic Tbx18 gene expression is epigenetically
      regulated during mouse limb development, we examined the methylation status of
      the CpG-island in the mouse Tbx18 gene by methylation-specific polymerase chain
      reaction. Hypermethylation of the Tbx18 gene promoter became evident at an early
      embryonic stage in TBX18-negative cells and then disappeared at a late embryonic
      stage in TBX18-positive cells. Therefore, the temporal suppression of Tbx18 gene
      expression by the hypermethylation of its promoter seems to trigger the
      differentiation of mesenchymal cells into hypertrophic chondrocytes in the early
      stages of endochondral ossification. 

PMID- 25380566
TI  - Clustering of Kir4.1 at specialized compartments of the lateral membrane in
      ependymal cells of rat brain.
AB  - Brain ependymal cells, which form an epithelial layer covering the cerebral
      ventricles, have been shown to play a role in the regulation of cerebrospinal and
      interstitial fluids. The machinery underlying this, however, remains largely
      unknown. Here, we report the specific localization of an inwardly rectifying K(+)
      channel, Kir4.1, on the ependymal cell membrane suggesting involvement of the
      channel in this function. Immunohistochemical study with confocal microscopy
      identified Kir4.1 labeling on the lateral but not apical membrane of ependymal
      cells. Ultrastructural analysis revealed that Kir4.1-immunogold particles were
      specifically localized and clustered on adjacent membranes at puncta adherens
      type junctions, whereas an aquaporin water channel, AQP4, that was also detected
      on the lateral membrane only occurred at components other than adherens
      junctions. Therefore, in ependymal cells, Kir4.1 and AQP4 are partitioned into
      distinct membrane compartments that might respectively transport either K(+) or
      water. Kir4.1 was also expressed in a specialized form of ependymal cell, namely
      the tanycyte, being abundant in tanycyte processes wrapping neuropils and blood
      vessels. These specific localizations suggest that Kir4.1 mediates intercellular
      K(+) exchange between ependymal cells and also K(+)-buffering transport via
      tanycytes that can interconnect neurons and vessels/ventricles. We propose that
      ependymal cells and tanycytes differentially operate Kir4.1 and AQP4 actively to
      control the property of fluids at local areas in the brain. 

PMID- 25380568
TI  - Ross River virus infection in a Thuringian traveller returning from south-east
      Australia.
AB  - Ross River virus (RRV) is an arbovirus transmitted by Aedes and Culex mosquitos.
      It is endemic in Australia, New Zealand and south-east Asia. Clinical
      manifestation rates in adults range about 20-40%. Symptoms involve arthralgia,
      myalgia, lymphadenopathy, fever and rash. Here we report a case of RRV in a
      Thuringian traveller who visited the urban South-East of Australia.

PMID- 25380567
TI  - The Amsterdam Sexual Abuse Case (ASAC)-study in day care centers: longitudinal
      effects of sexual abuse on infants and very young children and their parents, and
      the consequences of the persistence of abusive images on the internet.
AB  - BACKGROUND: Little research has been done on the signs of child sexual abuse
      (CSA) in infants and very young children, or on the consequences that such abuse 
      including the persistence of the abusive pornographic images on the internet -
      might have for the children and their parents. The effects of CSA can be severe,
      and a variety of risk- and protective factors, may influence those effects. CSA
      may affect the psychosocial-, emotional-, cognitive-, and physical development of
      children, their relationships with their parent(s), and the relations between
      parents. In the so called 'the Amsterdam sexual abuse case' (ASAC), infants and
      very young children were victimized by a day-care employee and most of the
      victims were boys. Research involving the children and their parents would enable
      recognition of the signs of CSA in very young children and understanding the
      consequences the abuse might have on the long term. METHODS/DESIGN: The proposed
      research project consists of three components: (I) An initial assessment to
      identify physical- or psychological signs of CSA in infants and very young
      children who are thought to have been sexually abused (n = 130); (II) A cross
      sequential longitudinal study of children who have experienced sexual abuse, or
      for whom there are strong suspicions; (III) A qualitative study in which
      interviews are conducted with parents (n = 25) and with therapists treating
      children from the ASAC. Parents will be interviewed on the perceived condition of
      their child and family situation, their experiences with the service responses to
      the abuse, the effects of legal proceedings and media attention, and the impact
      of knowing that pornographic material has been disseminated on the internet.
      Therapists will be interviewed on their clinical experiences in treating children
      and parents. The assessments will extend over a period of several years. The
      outcome measures will be symptoms of posttraumatic stress disorder (PTSD),
      dissociative symptoms, age-inappropriate sexual behaviors and knowledge,
      behavioral problems, attachment disturbances, the quality of parent-child
      interaction, parental PTSD, parental partner relation, and biological outcomes
      (BMI and DNA). DISCUSSION: The ASAC-project would facilitate early detection of
      symptoms and prompt therapeutic intervention when CSA is suspected in very young
      children.

PMID- 25380569
TI  - Severe thrombocytopenia in hantavirus-induced nephropathia epidemica.
AB  - Nephropathia epidemica is a milder form of hemorrhagic fever with renal syndrome,
      caused by Puumala virus. The clinical picture is characterized by a rapid loss of
      renal function (acute kidney injury) and thrombocytopenia. The purpose of the
      current analysis was to compare the clinical course of patients presenting with
      or without severe thrombocytopenia. In 47 out of 456 patients with acute
      nephropathia epidemica, the nadir count of thrombocytes was available for the
      acute course of the disease. The clinical course of these patients was further
      analyzed. No major bleeding (e.g., intracranial bleeding or gastrointestinal
      bleeding) occurred in either group. Creatinine peak levels were higher and
      proteinuria was more frequently present in the severely thrombocytopenic group.
      In conclusion, severe thrombocytopenia is common in nephropathia epidemica and is
      associated with a more severe course of the disease; however, bleeding
      complications are rare. 

PMID- 25380570
TI  - Osteoma of long bone: an expanding spectrum of imaging findings.
AB  - Osteoma of long bone is an extremely rare, benign bone-forming surface lesion
      with the largest published case series consisting of only 14 patients. The most
      important and often most difficult lesion to differentiate from osteoma of long
      bone radiographically is parosteal osteosarcoma, which is a rare, low-grade
      surface osteosarcoma with the potential for dedifferentiation. Reports of imaging
      studies of osteoma of long bone depict a well-defined ossified mass arising from
      the surface of the diaphysis or metadiaphysis of a long bone. A characteristic
      feature is the homogeneity of the mass, with uniform density near or equal to
      that of cortical bone from the base of the lesion to its periphery. The 45-year
      old female in this case presented with left hip fullness and was subsequently
      found to have a proximal femoral osteoma, which was unique in that it contained
      large fatty marrow spaces that corresponded to bands of relatively low density on
      plain radiography and computed tomography, giving it a heterogeneous appearance
      atypical of osteoma of long bone. Furthermore, the osteoma reported here was
      associated with a small but separate nodular focus of ossification in the
      adjacent soft tissue. These findings led to a presumptive diagnosis of parosteal
      osteosarcoma with a local soft tissue metastasis or satellite nodule resulting in
      radical resection of the tumor. Definitive diagnosis of osteoma was made on
      histology of both the parent lesion and ossified nodule as no neoplastic spindle
      cell proliferation was present to establish a diagnosis of low-grade
      osteosarcoma. This represents, to the best of our knowledge, the first such
      presentation of osteoma of long bone. 

PMID- 25380571
TI  - Preclinical assessment of a new magnetic resonance-based technique for
      determining bone quality by characterization of trabecular microarchitecture.
AB  - The utility of HR-CT to study longitudinal changes in bone microarchitecture is
      limited by subject radiation exposure. Although MR is not subject to this
      limitation, it is limited both by patient movement that occurs during prolonged
      scanning at distal sites, and by the signal-to-noise ratio that is achievable for
      high-resolution images in a reasonable scan time at proximal sites. Recently, a
      novel MR-based technique, fine structure analysis (FSA) (Chase et al. Localised
      one-dimensional magnetic resonance spatial frequency spectroscopy.
      PCT/US2012/068284 2012, James and Chase Magnetic field gradient structure
      characteristic assessment using one-dimensional (1D) spatial frequency
      distribution analysis. 7932720 B2, 2011) has been developed which provides both
      high-resolution and fast scan times, but which generates at a designated set of
      spatial positions (voxels) a one-dimensional signal of spatial frequencies.
      Appendix 1 provides a brief introduction to FSA. This article describes an
      initial exploration of FSA for the rapid, non-invasive characterization of
      trabecular microarchitecture in a preclinical setting. For L4 vertebrae of sham
      and ovariectomized (OVX) rats, we compared FSA-generated metrics with those from
      CT datasets and from CT-derived histomorphometry parameters, trabecular number
      (Tb.N), bone volume density (BV/TV), trabecular thickness (Tb.Th) and trabecular
      separation (Tb.Sp). OVX caused a reduction of the higher frequency structures
      that correspond to a denser trabecular lattice, while increasing the
      preponderance of lower frequency structures, which correspond to a more open
      lattice. As one example measure, the centroid of the FSA spectrum (which we refer
      to as fSAcB) showed strong correlation in the same region with CT-derived
      histomorphometry values: Tb.Sp: r -0.63, p < 0.001; Tb.N: r 0.71, p < 0.001;
      BV/TV: r 0.64, p < 0.001, Tb.Th: r 0.44, p < 0.05. Furthermore, we found a 17.5%
      reduction in fSAcB in OVX rats (p < 0.0001). In a longitudinal study, FSA showed
      that the age-related increase in higher frequency structures was abolished in OVX
      rats, being replaced with a 78-194% increase in lower frequency structures (2.4
      2.8 objects/mm range), indicating a more sparse trabecular lattice (p < 0.05).
      The MR-based fine structure analysis enables high-resolution, radiation-free,
      rapid quantification of bone structures in one dimension (the specific point and
      direction being chosen by the clinician) of the spine.

PMID- 25380572
TI  - Impact of tropomyosin isoform composition on fast skeletal muscle thin filament
      regulation and force development.
AB  - Tropomyosin (Tm) plays a central role in the regulation of muscle contraction and
      is present in three main isoforms in skeletal and cardiac muscles. In the present
      work we studied the functional role of alpha- and betaTm on force development by
      modifying the isoform composition of rabbit psoas skeletal muscle myofibrils and
      of regulated thin filaments for in vitro motility measurements. Skeletal
      myofibril regulatory proteins were extracted (78%) and replaced (98%) with Tm
      isoforms as homogenous alphaalphaTm or betabetaTm dimers and the functional
      effects were measured. Maximal Ca(2+) activated force was the same in
      alphaalphaTm versus betabetaTm myofibrils, but betabetaTm myofibrils showed a
      marked slowing of relaxation and an impairment of regulation under resting
      conditions compared to alphaalphaTm and controls. betabetaTm myofibrils also
      showed a significantly shorter slack sarcomere length and a marked increase in
      resting tension. Both these mechanical features were almost completely abolished
      by 10 mM 2,3-butanedione 2-monoxime, suggesting the presence of a significant
      degree of Ca(2+)-independent cross-bridge formation in betabetaTm myofibrils.
      Finally, in motility assay experiments in the absence of Ca(2+) (pCa 9.0),
      complete regulation of thin filaments required greater betabetaTm versus
      alphaalphaTm concentrations, while at full activation (pCa 5.0) no effect was
      observed on maximal thin filament motility speed. We infer from these
      observations that high contents of betabetaTm in skeletal muscle result in
      partial Ca(2+)-independent activation of thin filaments at rest, and longer
      lasting and less complete tension relaxation following Ca(2+) removal.

PMID- 25380574
TI  - CORR Insights(r): Medical services and associated costs vary widely among
      surgeons treating patients with hand osteoarthritis.

PMID- 25380573
TI  - Myogenic progenitors and imaging single-cell flow analysis: a model to study
      commitment of adult muscle stem cells.
AB  - Research on skeletal muscles suffers from a lack of appropriate human models to
      study muscle formation and regeneration on the regulatory level of single cells.
      This hampers both basic understanding and the development of new therapeutic
      approaches. The use of imaging multicolour flow cytometry and myogenic stem cells
      can help fill this void by allowing researchers to visualize and quantify the
      reaction of individual cultured cells to bioactives or other physiological
      impulses. As proof of concept, we subjected human CD56+ satellite cells to
      reference bioactives follistatin and Malva sylvestris extracts and then used
      imaging multicolor flow cytometry to visualize the stepwise activation of
      myogenic factors MyoD and myogenin in individual cells. This approach enabled us
      to evaluate the potency of these bioactives to stimulate muscle commitment. To
      validate this method, we used multi-photon confocal microscopy to confirm the
      potential of bioactives to stimulate muscle differentiation and expression of
      desmin. Imaging multicolor flow cytometry revealed statistically significant
      differences between treated and untreated groups of myogenic progenitors and we
      propose the utilization of this concept as an integral part of future muscle
      research strategies. 

PMID- 25380575
TI  - Reply to the letter to the editor: how does ulnar shortening osteotomy influence
      morphologic changes in the triangular fibrocartilage complex?

PMID- 25380576
TI  - BRCA1 alterations are associated with endometriosis, but BRCA2 alterations show
      no detectable endometriosis risk: a study in Indian population.
AB  - PURPOSE: To investigate the role of genetic variations and expression alterations
      of BRCA1 and BRCA2 genes in the pathophysiology of endometriosis. METHODS: A
      genetic association study was conducted in 573 endometriosis cases and 490
      controls of Indian origin. We genotyped 13 selected promoter SNPs of BRCA1 gene
      and 2 selected promoter SNPs of BRCA2 gene by PCR-sequencing analysis. In
      addition, to better understand genetic contributions to the pathophysiology of
      endometriosis, the expression pattern of BRCA1 & 2 was analyzed in the eutopic
      endometria of endometriosis cases and controls by western-blot and
      immunohistochemical analysis. RESULTS: Our results revealed significant
      association between BRCA1 rs71361504 (-/GTT) SNP and endometriosis risk in Indian
      women (P < 0.0001), while the remaining SNPs of both BRCA1 & 2 genes showed no
      difference between cases and controls. Western-blot and immunohistochemical
      analysis revealed significantly decreased BRCA1 expression levels in eutopic
      endometria of patients compared with controls (P < 0.05). Furthermore, nuclear
      BRCA1 was frequently lost compared with cytoplasmic BRCA1 in eutopic endometria
      of patients. Expression of BRCA2 did not differ between patients and controls.
      CONCLUSIONS: BRCA1 rs71361504 SNP may modify the endometriosis risk in Indian
      women. In addition, decreased expression of BRCA1 may play an important role in
      the pathophysiology of endometriosis. The analysis of BRCA1 genetic variants
      and/or expression might help to identify patients at high risk for disease
      outcome.

PMID- 25380578
TI  - Repair of gastric defects with an equine pericardial patch.
AB  - PURPOSES: The objective of this study was to test the efficacy of an equine
      pericardial patch for repairing full-thickness defects of the stomach wall.
      METHODS: Circular defects, 1.5 cm in diameter, were created on the anterior wall
      of the stomach of 12 female New Zealand rabbits. The defects were repaired by an
      equine pericardial patch. After euthanasia at different time intervals (3 days to
      8 weeks) a macroscopic evaluation of the abdominal cavity (including adhesion
      scoring), mechanical testing and a histological examination of the stomach were
      performed. RESULTS: The animals survived the surgical procedure and underwent an
      uneventful recovery until euthanasia. None of the patches failed. Adhesions were
      observed in all animals and were significant in 3/12 animals. Bursting pressure
      testing indicated that the repair was durable and that adequate strength to
      prevent patch failure was achieved by the second week. A histological examination
      showed gradual narrowing of the perforation site by mucosal and limited muscular
      regeneration. CONCLUSIONS: The equine pericardial patch was successfully used to
      repair a gastric defect in our experimental model, and it seems that it could
      have potential as a material suitable for further research concerning the repair
      of upper gastrointestinal defects.

PMID- 25380577
TI  - Functional Histology of Salivary Gland Pleomorphic Adenoma: An Appraisal.
AB  - The complex microstructure of salivary gland pleomorphic adenoma is examined in
      relation to function. Events related to secretion of macromolecules and
      absorption, responses to the altered microenvironment and controversies
      concerning epithelial-mesenchymal transition versus modified myoepithelial
      differentiation are explored. Their effects on tumor cell phenotypes and
      arrangements are emphasized. Heterotopic differentiation and attempts at
      organogenesis are also considered. The approach allows interpreting
      microstructure independently of histogenetic perceptions, envisaging the tumor
      cells as a continuum, endorsing luminal structures as the principal components,
      and defining pleomorphic adenoma as a benign epithelial tumour characterized by
      variable epithelial-mesenchymal transition, secretion/differentiation and
      metaplasia. 

PMID- 25380579
TI  - The effect of cobalt on the human eye.
AB  - PURPOSE: The effect of elevated serum cobalt on the human visual system has not
      yet been established. In light of recent reports of visual problems with elevated
      cobalt in association with hip prostheses, this review examines the literature
      for evidence regarding the effects of cobalt on human visual function. METHODS: A
      systematic literature review was undertaken in July 2013. The electronic
      databases of PubMed (1955 to July week 1 2013), Cochrane Library and EMBASE were
      searched. Only human studies or case reports written in English were included.
      RESULTS: Eight case reports were identified. Five case reports involved patients
      with metal hip arthroplasties, two cases involved patients exposed to
      environmental cobalt, and one case involved a patient treated medically for
      anaemia with cobalt chloride. No human prospective studies were identified.
      CONCLUSIONS: Several case reports showed that high serum cobalt may be associated
      with both irreversible and reversible visual loss, optic neuropathy and atrophy,
      electrophysiological evidence of abnormal retinal and retinal pigment epithelium
      function and fluorescein angiographic evidence of abnormal choroidal perfusion.

PMID- 25380580
TI  - Runx2, a target gene for activating transcription factor-3 in human breast cancer
      cells.
AB  - Activating transcription factor (ATF-3) is a stress response gene and is induced
      by transforming growth factor beta 1 (TGF-beta1) in breast cancer cells. In this
      study, we dissected the functional role of ATF-3 gene in vitro by knocking down
      its expression stably in human bone metastatic breast cancer cells (MDA-MB231).
      Knockdown of ATF-3 expression in these cells decreased cell number, altered cell
      cycle phase transition, and decreased mRNA expression of cell cycle genes.
      Knockdown of ATF-3 expression in MDA-MB231 cells also decreased cell migration,
      and the expression levels of invasive and metastatic genes such as MMP-13 and
      Runx2 were found to be decreased in these cells. Most importantly, ATF-3 was
      associated with Runx2 promoter in MDA-MB231 cells and knockdown of ATF-3
      expression decreased its association with Runx2 promoter. Hence, our results
      suggested that ATF-3 plays a role in proliferation and invasion of bone
      metastatic breast cancer cells in vitro and we identified for the first time that
      Runx2 is a target gene of ATF-3 in MDA-MB231 cell line. 

PMID- 25380581
TI  - A retrospective cohort study of patients with stomach and liver cancers: the
      impact of comorbidity and ethnicity on cancer care and outcomes.
AB  - BACKGROUND: Comorbidity has an adverse impact on cancer survival partly through
      its negative impact on receipt of curative treatment. Comorbidity is unevenly
      distributed within populations, with some ethnic and socioeconomic groups having
      considerably higher burden. The aim of this study was to investigate the inter
      relationships between comorbidity, ethnicity, receipt of treatment, and cancer
      survival among patients with stomach and liver cancer in New Zealand. METHODS:
      Using the New Zealand Cancer Registry, Maori patients diagnosed with stomach and
      liver cancers were identified (n = 269), and compared with a randomly selected
      group of non-Maori patients (n = 255). Clinical and outcome data were collected
      from medical records, and the administrative hospitalisation and mortality
      databases. Logistic and Cox regression modelling with multivariable adjustment
      were used to examine the impacts of ethnicity and comorbidity on receipt of
      treatment, and the impact of these variables on all-cause and cancer specific
      survival. RESULTS: More than 70% of patients had died by two years post
      diagnosis. As comorbidity burden increased among those with Stage I-III disease,
      the likelihood that the patient would receive curative surgery decreased (e.g. C3
      Index score 6 vs 0, adjusted OR: 0.32, 95% CI 0.13-0.78) and risk of mortality
      increased (e.g. C3 Index score 6 vs 0, adjusted all-cause HR: 1.44, 95% CI 0.93
      2.23). Receipt of curative surgery reduced this excess mortality, in some cases
      substantially; but the extent to which this occurred varied by level of
      comorbidity. Maori patients had somewhat higher levels of comorbidity (34% in
      highest comorbidity category compared with 23% for non-Maori) and poorer survival
      that was not explained by age, sex, site, stage, comorbidity or receipt of
      curative surgery (adjusted cancer-specific HR: 1.36, 95% CI 0.97-1.90; adjusted
      all-cause HR: 1.33, 95% CI 0.97-1.82). Access to healthcare factors accounted for
      25-36% of this survival difference. CONCLUSIONS: Patients with comorbidity were
      substantially less likely to receive curative surgery and more likely to die than
      those without comorbidity. Receipt of curative surgery markedly reduced their
      excess mortality. Despite no discernible difference in likelihood of curative
      treatment receipt, Maori remained more likely to die than non-Maori even after
      adjusting for confounding and mediating variables.

PMID- 25380582
TI  - Factors influencing the clinical expression of intermediate CAG repeat length
      mutations of the Huntington's disease gene.
AB  - Our aim is to elucidate the clinical variables associated with the development of
      manifest HD in patients with intermediate CAG repeat lengths. 2,167 participants
      were seen throughout 44 research sites in the United States, Canada or Australia
      over a five-year natural history observational study (2006-2011) (Trial #
      NCT00313495). The Chi-square test and a generalised linear model were used to
      examine the differences in demographics and cognitive tests among three groups of
      CAG repeat length. The mixed model was then used to examine the time effect on
      cognitive assessments by CAG groups. No patient with CAG repeat length 27-35
      developed manifest HD, whereas three patients with 36-39 did. Total motor score,
      maximal chorea score and maximal dystonia score were significantly different at
      baseline (p < 0.001) for each measure between those patients with a repeat length
      27-35 versus those 36-39; as were total functional assessment, independence scale
      and total functional capacity (p < 0.001). Being aged 65 years or more (OR 5.81,
      95 % CI 0.37-90.58, p = 0.02) and smoking (OR 13.99, 95 % CI 2.03-96.44, p =
      0.007) were related to manifest HD in patients with CAG 36-39; those with an
      associated university degree or higher education were less frequently diagnosed
      as manifest HD (OR 0.10, 95 % CI 0.02-0.54, p = 0.007). Age, smoking and lower
      education achievement were found to be significantly associated with higher odds
      of manifest HD in patients with intermediate CAG repeat length mutations.

PMID- 25380583
TI  - Correlates of cerebrospinal fluid levels of oligomeric- and total-alpha-synuclein
      in premotor, motor and dementia stages of Parkinson's disease.
AB  - High-oligomeric and low-total-alpha-synuclein cerebrospinal fluid (CSF) levels
      have been found in Parkinson's disease (PD), but with inconsistent or limited
      data, particularly on their clinical and structural correlates in earliest
      (premotor) or latest (dementia) PD stages. We determined CSF oligomeric- and
      total-alpha-synuclein in 77 subjects: 23 with idiopathic REM-sleep behaviour
      disorder (iRBD, a condition likely to include a remarkable proportion of subjects
      in the premotor stage of PD) and 41 with PD [21 non-demented (PDND) + 20 demented
      (PDD)], intended to reflect the premotor-motor-dementia PD continuum, along with
      13 healthy controls. The study protocol also included the Unified PD Rating Scale
      motor-section (UPDRS-III), mini mental state examination (MMSE),
      neuropsychological cognitive testing, 3T brain MRI for cortical-thickness
      analyses, CSF tau and CSF Abeta. CSF oligomeric-alpha-synuclein was higher in
      PDND than iRBD and in PDD than iRBD and controls, and correlated with UPDRS-III,
      MMSE, semantic fluency and visuo-perceptive scores across the proposed premotor
      motor-dementia PD continuum (iRBD + PDND + PDD). CSF total-alpha-synuclein
      positively correlated with age, CSF Abeta, and, particularly, CSF tau, tending
      towards lower levels in PD (but not iRBD) vs. controls only when controlling for
      CSF tau. Low CSF total-alpha-synuclein was associated with dysfunction in
      phonetic-fluency (a frontal-lobe function) in PD and with frontal cortical
      thinning in iRBD and PDND independently of CSF tau. Conversely, the associations
      of high (instead of low) CSF total-alpha-synuclein with posterior-cortical
      neuropsychological deficits in PD and with posterior cortical thinning in PDD
      were driven by high CSF tau. These findings suggest that CSF oligomeric- and
      total-alpha-synuclein have different clinical, neuropsychological and MRI
      correlates across the proposed premotor-motor-dementia PD continuum. CSF total
      alpha-synuclein correlations with CSF tau and Abeta support the hypothesis of an
      interaction among these proteins in PD, with CSF tau probably influencing the
      presence of high (instead of low) CSF total-alpha-synuclein and its correlates
      mostly in the setting of PD-related dementia. 

PMID- 25380584
TI  - Crossed aphasia and preserved visuospatial functions in logopenic variant primary
      progressive aphasia.

PMID- 25380585
TI  - Natural history of skeletal muscle involvement in myotonic dystrophy type 1: a
      retrospective study in 204 cases.
AB  - Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adult.
      The aim of this study was to investigate the natural history of skeletal muscle
      weakness in adults, in a cross-sectional, retrospective study. In a cohort of 204
      adult DM1 patients, we quantified muscle impairment, handgrip force and physical
      disability. Muscle strength was similarly affected in the legs and in the arms,
      the right and left side, and distally more than proximally in patients. The
      earliest and the most affected skeletal muscles were the digit flexors, foot
      dorsiflexors and neck flexors; whereas the elbow and knee extensors and flexors
      were the least affected muscle groups. The rate of decline of the muscle strength
      was -0.111 units/year. The handgrip values were lower in DM1 patients than the
      normative values and the rate of decline in handgrip force per year was -0.24 kg.
      Limitation in mobility or walking is observed in 84 % of DM1 patients but
      requirement of wheelchair is infrequent (3 %). The decrease in muscle strength,
      handgrip force and the increase in physical disability were highly correlated
      with duration of the disease and the number of CTG repeats in the blood.
      Significant association was found between decline in muscle strength and the age
      at onset, physical disability and the age of patients at evaluation, handgrip
      force and gender. Decline in muscle weakness is very slow and although limitation
      when walking is a common manifestation of DM1 in patients, the requirement of
      wheelchair is infrequent.

PMID- 25380586
TI  - Nitric oxide synthase inhibitors: a review of patents from 2011 to the present.
AB  - INTRODUCTION: Nitric oxide synthases (NOSs) are a family of enzymes that play an
      essential role in synthesizing nitric oxide (NO) by oxidizing l-arginine. As
      previously reported, NO is a significant mediator in cellular signaling pathways.
      It serves as a crucial regulator in insulin secretion, vascular tone,
      peristalsis, angiogenesis, neural development and inflammation. Due to its
      important role, the inhibition of these vital enzymes provides, as tools, the
      opportunity to gain an insight into potential therapeutic applications targeting
      NOSs. AREAS COVERED: This paper reviews the patent literature between 2011 and
      mid-2014 that specified inhibitors of NOS family members as the significant
      targets. Google and Baidu search engines were used to find relevant patents and
      clinical information using NOSs or NOS inhibitor as search terms. EXPERT OPINION:
      Considerable recent progress has been made in the development of NOS inhibitors
      with pharmacodynamic and pharmacokinetic properties, and such development is
      likely to continue. The patented compounds attenuated mostly embodying evidence
      from in vitro and in vivo trials that demonstrate good potential for future
      clinical human trials and industrial applications. Furthermore, new techniques
      such as X-ray ligand crystallographic study and structure-activity relationship
      were popularly utilized, which give new insights for developing novel, safe,
      efficient and selective NOS inhibitors.

PMID- 25380587
TI  - Nutrition and the prevalence of dementia in mainland China, Hong Kong, and
      Taiwan: an ecological study.
AB  - BACKGROUND: Western diets are associated with obesity, vascular diseases, and
      metabolic syndrome and might increase dementia risk in later life. If these
      associations are causal, those low- and middle-income countries experiencing
      major changes in diet might also see an increasing prevalence of dementia.
      OBJECTIVE: To investigate the relationship of dietary supply and the prevalence
      of dementia in mainland China, Hong Kong, and Taiwan over time using existing
      data and taking diagnostic criteria into account. METHODS: Estimated total energy
      supply and animal fat from the United Nations was linked to the 70 prevalence
      studies in mainland China, Hong Kong, and Taiwan from 1980 to 2012 according to
      the current, 10 years, and 20 years before starting year of investigation.
      Studies using newer and older diagnostic criteria were separated into two groups.
      Spearman's rank correlation was calculated to investigate whether trends in total
      energy, animal fat supply, and prevalence of dementia were monotonically related.
      RESULTS: The supply of total energy and animal fat per capita per day in China
      increased considerably over the last 50 years. The original positive relationship
      of dietary supply and dementia prevalence disappeared after stratifying by newer
      and older diagnostic criteria and there was no clear time lag effect. CONCLUSION:
      Taking diagnostic criteria into account, there is no cross-sectional or time lag
      relationship between the dietary trends and changes in dementia prevalence. It
      may be too early to detect any such changes because current cohorts of older
      people did not experience these dietary changes in their early to mid-life.

PMID- 25380588
TI  - Integrated whole transcriptome and DNA methylation analysis identifies gene
      networks specific to late-onset Alzheimer's disease.
AB  - Previous transcriptome studies observed disrupted cellular processes in late
      onset Alzheimer's disease (LOAD), yet it is unclear whether these changes are
      specific to LOAD, or are common to general neurodegeneration. In this study, we
      address this question by examining transcription in LOAD and comparing it to
      cognitively normal controls and a cohort of "disease controls." Differential
      transcription was examined using RNA-seq, which allows for the examination of
      protein coding genes, non-coding RNAs, and splicing. Significant transcription
      differences specific to LOAD were observed in five genes: C10orf105, DIO2, a
      lincRNA, RARRES3, and WIF1. These findings were replicated in two independent
      publicly available microarray data sets. Network analyses, performed on 2,504
      genes with moderate transcription differences in LOAD, reveal that these genes
      aggregate into seven networks. Two networks involved in myelination and innate
      immune response specifically correlated to LOAD. FRMD4B and ST18, hub genes
      within the myelination network, were previously implicated in LOAD. Of the five
      significant genes, WIF1 and RARRES3 are directly implicated in the myelination
      process; the other three genes are located within the network. LOAD specific
      changes in DNA methylation were located throughout the genome and substantial
      changes in methylation were identified within the myelination network. Splicing
      differences specific to LOAD were observed across the genome and were decreased
      in all seven networks. DNA methylation had reduced influence on transcription
      within LOAD in the myelination network when compared to both controls. These
      results hint at the molecular underpinnings of LOAD and indicate several key
      processes, genes, and networks specific to the disease. 

PMID- 25380589
TI  - A comprehensive visual rating scale of brain magnetic resonance imaging:
      application in elderly subjects with Alzheimer's disease, mild cognitive
      impairment, and normal cognition.
AB  - BACKGROUND: Brain magnetic resonance imaging (MRI) shows cerebral structural
      changes. However, a unified comprehensive visual rating scale (CVRS) has seldom
      been studied. Thus, we combined brain atrophy and small vessel disease scales and
      used an MRI template as a CVRS. OBJECTIVE: The aims of this study were to design
      a simple and reliable CVRS, validate it by investigating cerebral structural
      changes in clinical groups, and made comparison to the volumetric measurements.
      METHODS: Elderly subjects (n = 260) with normal cognition (NC, n = 65), mild
      cognitive impairment (MCI, n = 101), or Alzheimer's disease (AD, n = 94) were
      evaluated with brain MRI according to the CVRS of brain atrophy and small vessel
      disease. Validation of the CVRS with structural changes, neuropsychological
      tests, and volumetric analyses was performed. RESULTS: The CVRS revealed a high
      intra-rater and inter-rater agreement and it reflected the structural changes of
      subjects with NC, MCI, and AD better than volumetric measures (CVRS-coronal: F =
      13.5, p < 0.001; CVRS-axial: F = 19.9, p < 0.001). The area under the receiver
      operation curve (aROC) of the CVRS showed higher accuracy than volumetric
      analyses. (NC versus MCI aROC: CVRS-coronal, 0.777; CVRS-axial, 0.773; MCI versus
      AD aROC: CVRS-coronal, 0.680; CVRS-axial, 0.681). CONCLUSION: The CVRS can be
      used clinically to conveniently measure structural changes of brain. It reflected
      cerebral structural changes of clinical groups and correlated with the age better
      than volumetric measures.

PMID- 25380590
TI  - Memory impairment in rats after desflurane anesthesia is age and dose dependent.
AB  - Post-operative cognitive dysfunction (POCD) predominantly affects the elderly who
      suffer memory and concentration deficits after anesthesia and surgery. Animal
      studies have demonstrated anesthetic alone may contribute to POCD but results are
      variable and little is known about common anesthetics other than isoflurane. The
      present study investigated dose-dependence of desflurane anesthesia in young
      adult and aged rats. We hypothesize higher concentrations of desflurane will
      result in memory impairment in the water maze and that impairment will be worse
      in aged rats. Effects of anesthesia (1 or 1.5 MAC, 4 h) desflurane, or sham
      exposure on cognition were investigated in young adult (3 months) and aged (20-24
      months) rats at 1, 4, and 12 weeks post-exposure. The Morris water maze was used
      to assess acquisition and retention of spatial reference memory. Latency to find
      the hidden platform and swimming speed were compared between treatments. Aged
      rats showed significant impairment in task acquisition after exposure to 1.5 MAC,
      but not 1.0 MAC desflurane anesthetic when tested 1 week following exposure.
      Latency to find the platform and distance travelled were significantly longer in
      aged rats given 1.5 MAC desflurane (latency: F(1,108) = 19.71, p < 0.0001;
      distance: F(1,108) = 5.79, p = 0.018). Deficits were not long-lasting and were no
      longer present at 4 or 12 weeks. In contrast, young adult rats performed equally
      as well as sham-exposed control rats irrespective of desflurane dose. This study
      showed the effects of desflurane on learning and memory in the water maze are age
      and dose dependent and are brief in duration. 

PMID- 25380591
TI  - Downsizing of lean body mass is a key determinant of Alzheimer's disease.
AB  - Lean body mass (LBM) encompasses all metabolically active organs distributed into
      visceral and structural tissue compartments and collecting the bulk of N and K
      stores of the human body. Transthyretin (TTR) is a plasma protein mainly secreted
      by the liver within a trimolecular TTR-RBP-retinol complex revealing from birth
      to old age strikingly similar evolutionary patterns with LBM in health and
      disease. TTR is also synthesized by the choroid plexus along distinct regulatory
      pathways. Chronic dietary methionine (Met) deprivation or cytokine-induced
      inflammatory disorders generates LBM downsizing following differentiated
      physiopathological processes. Met-restricted regimens downregulate the
      transsulfuration cascade causing upstream elevation of homocysteine (Hcy)
      safeguarding Met homeostasis and downstream drop of hydrogen sulfide (H2S)
      impairing anti-oxidative capacities. Elderly persons constitute a vulnerable
      population group exposed to increasing Hcy burden and declining H2S protection,
      notably in plant-eating communities or in the course of inflammatory illnesses.
      Appropriate correction of defective protein status and eradication of
      inflammatory processes may restore an appropriate LBM size allowing the hepatic
      production of the retinol circulating complex to resume, in contrast with the
      refractory choroidal TTR secretory process. As a result of improved health
      status, augmented concentrations of plasma-derived TTR and retinol may reach the
      cerebrospinal fluid and dismantle senile amyloid plaques, contributing to the
      prevention or the delay of the onset of neurodegenerative events in elderly
      subjects at risk of Alzheimer's disease. 

PMID- 25380593
TI  - Long Latency Auditory Evoked Potentials during Meditation.
AB  - The auditory sensory pathway has been studied in meditators, using midlatency and
      short latency auditory evoked potentials. The present study evaluated long
      latency auditory evoked potentials (LLAEPs) during meditation. Sixty male
      participants, aged between 18 and 31 years (group mean+/-SD, 20.5+/-3.8 years),
      were assessed in 4 mental states based on descriptions in the traditional texts.
      They were (a) random thinking, (b) nonmeditative focusing, (c) meditative
      focusing, and (d) meditation. The order of the sessions was randomly assigned.
      The LLAEP components studied were P1 (40-60 ms), N1 (75-115 ms), P2 (120-180 ms),
      and N2 (180-280 ms). For each component, the peak amplitude and peak latency were
      measured from the prestimulus baseline. There was significant decrease in the
      peak latency of the P2 component during and after meditation (P<.001; analysis of
      variance and post hoc analysis with Bonferroni adjustment). The P1, P2, and N2
      components showed a significant decrease in peak amplitudes during random
      thinking (P<.01; P<.001; P<.01, respectively) and nonmeditative focused thinking
      (P<.01; P<.01; P<.05, respectively). The results suggest that meditation
      facilitates the processing of information in the auditory association cortex,
      whereas the number of neurons recruited was smaller in random thinking and non
      meditative focused thinking, at the level of the secondary auditory cortex,
      auditory association cortex and anterior cingulate cortex.

PMID- 25380592
TI  - Potentially suboptimal prescribing for older veteran nursing home patients with
      dementia.
AB  - BACKGROUND: Nursing home patients with dementia may be more likely to suffer
      adverse drug events from suboptimal prescribing. Previous studies have not used
      national samples, nor have they examined multiple types of suboptimal prescribing
      by dementia severity. OBJECTIVE: To examine the prevalence of and factors
      associated with potentially suboptimal prescribing in older veteran nursing home
      patients with dementia. METHODS: This is a retrospective descriptive study of
      1303 veterans 65 years or older admitted between January 1, 2004, and June 30,
      2005, with dementia for long stays (90+ days) to 133 Veterans Affairs Community
      Living Centers. Dementia severity was determined by the Cognitive Performance
      Scale and functional status dependences. RESULTS: Overall, 70.2% with mild
      moderate dementia (n = 1076) had underuse because they did not receive an
      acetylcholinesterase inhibitor (AChEI), and 27.2% had evidence of inappropriate
      use because of a drug-disease or drug-drug-disease interaction. Of the 227 with
      severe dementia, 36.1% had overuse by receiving an AChEI or lipid-lowering or
      other agents, and 25.1% had evidence of inappropriate use as a result of a drug
      disease or drug-drug interaction. Multinomial logistic regression analyses among
      those with mild to moderate dementia identified that living in the South versus
      other regions was the single factor associated with all 3 types of suboptimal
      prescribing. In those with severe dementia, antipsychotic use was associated with
      all 3 suboptimal prescribing types. CONCLUSIONS: Potentially suboptimal
      prescribing was common in older veteran nursing home patients with dementia.
      Clinicians should develop a heightened awareness of these problems. Future
      studies should examine associations between potentially suboptimal prescribing
      and health outcomes in patients with dementia.

PMID- 25380595
TI  - India's ambition to eliminate visceral leishmaniasis.

PMID- 25380594
TI  - Global quality of life modifies terminal change in physical functioning among
      older adult women.
AB  - BACKGROUND: the factors that moderate decline in physical functioning as death
      approaches are understudied. This study aimed to assess death-related decline in
      global quality of life (QoL) and physical functioning and to test whether
      baseline QoL moderates terminal decline in physical functioning. METHODS: four
      thousand six hundred and fifty-one decedents from the Women's Health Initiative
      Study (WHI) rated QoL and physical functioning each year throughout 5 years of
      follow-up. RESULTS: both QoL and physical functioning showed a steeper decline as
      a function of years to death than as a function of chronological age. Moreover,
      decedents with higher QoL at baseline showed a less steep decline in physical
      functioning as death approached than those with lower QoL at baseline.
      CONCLUSION: although QoL strongly decreases across the terminal years, its
      beneficial influence on physical functioning is evident till the very end of
      life.

PMID- 25380596
TI  - Translatome profiling: methods for genome-scale analysis of mRNA translation.
AB  - During the past decade, there has been a rapidly increased appreciation of the
      role of translation as a key regulatory node in gene expression. Thereby, the
      development of methods to infer the translatome, which refers to the entirety of
      mRNAs associated with ribosomes for protein synthesis, has facilitated the
      discovery of new principles and mechanisms of translation and expanded our view
      of the underlying logic of protein synthesis. Here, we review the three main
      methodologies for translatome analysis, and we highlight some of the recent
      discoveries made using each technique. We first discuss polysomal profiling, a
      classical technique that involves the separation of mRNAs depending on the number
      of bound ribosomes using a sucrose gradient, and which has been combined with
      global analysis tools such as DNA microarrays or high-throughput RNA sequencing
      to identify the RNAs in polysomal fractions. We then introduce ribosomal
      profiling, a recently established technique that enables the mapping of ribosomes
      along mRNAs at near-nucleotide resolution on a global scale. We finally refer to
      ribosome affinity purification techniques that are based on the cell-type
      specific expression of tagged ribosomal proteins, allowing the capture of
      translatomes from specialized cells in organisms. We discuss the advantages and
      disadvantages of these three main techniques in the pursuit of defining the
      translatome, and we speculate about future developments. 

PMID- 25380598
TI  - Putting things in order.

PMID- 25380597
TI  - Interference-mediated synaptonemal complex formation with embedded crossover
      designation.
AB  - Biological systems exhibit complex patterns at length scales ranging from the
      molecular to the organismic. Along chromosomes, events often occur stochastically
      at different positions in different nuclei but nonetheless tend to be relatively
      evenly spaced. Examples include replication origin firings, formation of
      chromatin loops along chromosome axes and, during meiosis, localization of
      crossover recombination sites ("crossover interference"). We present evidence in
      the fungus Sordaria macrospora that crossover interference is part of a broader
      pattern that includes synaptonemal complex (SC) nucleation. This pattern
      comprises relatively evenly spaced SC nucleation sites, among which a subset are
      crossover sites that show a classical interference distribution. This pattern
      ensures that SC forms regularly along the entire length of the chromosome as
      required for the maintenance of homolog pairing while concomitantly having
      crossover interactions locally embedded within the SC structure as required for
      both DNA recombination and structural events of chiasma formation. This pattern
      can be explained by a threshold-based designation and spreading interference
      process. This model can be generalized to give diverse types of related and/or
      partially overlapping patterns, in two or more dimensions, for any type of
      object. 

PMID- 25380599
TI  - Multisystem physiologic impairments and changes in gait speed of older adults.
AB  - BACKGROUND: Slowed gait is an important health indicator in older adults but a
      single identifiable cause is often lacking. We assessed whether a summary index
      measuring impairments across multiple physiologic systems was associated with
      slowed gait in older individuals. METHODS: Data from the Cardiovascular Health
      Study (n = 3,010) were used to assess associations between baseline physiologic
      index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism;
      range 0-10 with 0-2 points/system and lower score indicating higher function) and
      annual gait speed (m/s) over 6 years. Participants with complete data on the
      physiologic index and at least two gait speed measures were included. Mean gait
      speed and 95% confidence intervals (CI) by category of index were calculated
      using mixed effects models. RESULTS: Those with scores of three or higher on the
      index had significantly slower gait speed at baseline compared to those with
      scores of 0-2 (7-10: mean speed = 0.83 m/s, 95% CI: 0.80, 0.84; 0-2: mean speed =
      1.01 m/s, 95% CI: 0.99, 1.03). Those with higher indices also had faster decline
      in gait speed compared to those with lower scores after adjustment for
      demographic and health characteristics (7-10: change in speed = -0.020 m/s/year,
      95% CI: -0.024, -0.016; 0-2: change in speed= -0.010 m/s/year, 95% CI: -0.014, 
      0.006). CONCLUSIONS: Greater impairment across five organ systems was associated
      with slower gait speed and greater declines in gait speed over 6 years.
      Impairments accumulated over multiple physiologic systems may make older adults
      more vulnerable to slow gait speed.

PMID- 25380600
TI  - Nordihydroguaiaretic Acid Extends the Lifespan of Drosophila and Mice, Increases
      Mortality-Related Tumors and Hemorrhagic Diathesis, and Alters Energy Homeostasis
      in Mice.
AB  - Mesonordihydroguaiaretic acid (NDGA) extends murine lifespan. The studies
      reported here describe its dose dependence, effects on body weight, toxicity
      related clinical chemistries, and mortality-related pathologies. In flies, we
      characterized its effects on lifespan, food consumption, body weight, and
      locomotion. B6C3F1 mice were fed AIN-93M diet supplemented with 1.5, 2.5, 3.5, or
      4.5 g NDGA/kg diet (1.59, 2.65, 3.71 and 4.77 mg/kg body weight/day) beginning at
      12 months of age. Only the 3.5 mg/kg diet produced a highly significant increase
      in lifespan, as judged by either the Mantel-Cox log-rank test (p = .008) or the
      Gehan-Breslow-Wilcoxon test (p = .009). NDGA did not alter food intake, but dose
      responsively reduced weight, suggesting it decreased the absorption or increased
      the utilization of calories. NDGA significantly increased the incidence of liver,
      lung, and thymus tumors, and peritoneal hemorrhagic diathesis found at necropsy.
      However, clinical chemistries found little evidence for overt toxicity. While
      NDGA was not overtly toxic at its therapeutic dosage, its association with severe
      end of life pathologies does not support the idea that NDGA consumption will
      increase human lifespan or health-span. The less toxic derivatives of NDGA which
      are under development should be explored as anti-aging therapeutics.

PMID- 25380603
TI  - Myelination Delay and Allan-Herndon-Dudley Syndrome Caused by a Novel Mutation in
      the SLC16A2 Gene.
AB  - Allan-Herndon-Dudley syndrome is an X-linked disease caused by mutations in the
      solute carrier family 16 member 2 (SLC16A2) gene. As SLC16A2 encodes the
      monocarboxylate transporter 8 (MCT8), a thyroid hormone transporter, patients
      with Allan-Herndon-Dudley syndrome present a specific altered thyroid hormone
      profile. Allan-Herndon-Dudley syndrome has been associated with myelination delay
      on the brain magnetic resonance imaging (MRI) of affected subjects. We report a
      patient with Allan-Herndon-Dudley syndrome characterized by developmental delay,
      hypotonia, and delayed myelination caused by a novel SLC16A2 mutation (p.L291R).
      The thyroid hormones profile in our patient was atypical for Allan-Herndon-Dudley
      syndrome. The follow-up examinations showed that the progression of the
      myelination was not accompanied by a clinical improvement. Our paper suggests
      that SLC16A2 mutations should be investigated in patients with myelination delay
      even when the thyroid function is not conclusively altered. 

PMID- 25380601
TI  - Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term
      survival.
AB  - BRCA1-associated protein-1 (BAP1) mutations cause a new cancer syndrome, with a
      high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM
      associated with germline BAP1 mutations has a better prognosis compared with
      sporadic MM. We compared survival among germline BAP1 mutation MM patients with
      that of all MM (N = 10 556) recorded in the United States Surveillance,
      Epidemiology, and End Results (SEER) data from 1973 to 2010. We identified 23 MM
      patients--11 alive--with germline BAP1 mutations and available data on survival.
      Ten patients had peritoneal MM, ten pleural MM and three MM in both locations.
      Thirteen patients had one or more malignancies in addition to MM. Actuarial
      median survival for the MM patients with germline BAP1 mutations was 5 years, as
      compared with <1 year for the median survival in the United States SEER MM group.
      Five-year survival was 47%, 95% confidence interval (24-67%), as compared with
      6.7% (6.2-7.3%) in the control SEER group. Analysis of the pooled cohort of
      germline BAP1 mutation MM showed that patients with peritoneal MM (median
      survival of 10 years, P = 0.0571), or with a second malignancy in addition to MM
      (median survival of 10 years, P = 0.0716), survived for a longer time compared
      with patients who only had pleural MM, or MM patients without a second
      malignancy, respectively. In conclusion, we found that MM patients with germline
      BAP1 mutations have an overall 7-fold increased long-term survival, independently
      of sex and age. Appropriate genetic counseling and clinical management should be
      considered for MM patients who are also BAP1 mutation carriers.

PMID- 25380602
TI  - Neonatal Neurocritical Care Service Is Associated With Decreased Administration
      of Seizure Medication.
AB  - This cohort study examines medication use in term neonates with hypoxic-ischemic
      encephalopathy and seizures before and after implementation of a Neonatal
      Neurocritical Care Service (N = 108), which included increased seizure
      monitoring. Nearly all neonates received phenobarbital (96% pre- vs 95% post
      Neonatal Neurocritical Care Service) and total loading dose did not vary among
      groups (33 [95% confidence interval 29-37] vs 30 [26-34] mg/kg). After adjustment
      for seizure burden, neonates managed during the Neonatal Neurocritical Care
      Service era, on average, received 30 mg/kg less cumulative phenobarbital (95%
      confidence interval 15-46 mg/kg) and were on maintenance 5 fewer days (95%
      confidence interval 3-8 days) than those who were treated prior to implementation
      of the service. In spite of the enhanced ability to detect seizures because of
      improved monitoring and increased vigilance by bedside practitioners,
      implementation of the Neonatal Neurocritical Care Service was associated with
      decreased use of potentially harmful phenobarbital treatment among neonates with
      hypoxic-ischemic encephalopathy. 

PMID- 25380604
TI  - Physical and mental workload in single-incision laparoscopic surgery and
      conventional laparoscopy.
AB  - OBJECTIVES: The aim of the present study is to evaluate mental workload and
      fatigue in fingers, hand, arm, shoulder in single-incision laparoscopic surgery
      (SILS) and multiport laparoscopy. METHODS: Volunteers performed chosen tasks by
      standard laparoscopy and SILS. Time to complete tasks and finger and hand
      strength were evaluated. Lateral, tripod, and pulp pinch strengths were measured.
      Hand dexterity was determined by pegboard. Electromyography recordings were taken
      from biceps and deltoid muscles of both extremities. The main outcome measurement
      was median frequency (MF) slope. NASA-TLX was used for mental workload. RESULTS:
      Time to complete laparoscopic tasks were longer in the SILS group (P < .05).
      Decrease of strength in fingers and hand were similar in SILS and standard
      laparoscopy. Pegboard time was increased in both hands after SILS (P < .05). MF
      slope of biceps muscle and deltoid muscle in SILS was far away from the reference
      slope. MF slope of biceps muscle and deltoid muscle in standard laparoscopy was
      close to reference slope, indicating there was more fatigue in biceps and deltoid
      muscles of both upper extremities in SILS group. NASA-TLX score was 73 +/- 13.3
      and 42 +/- 19.5 in SILS and multiport laparoscopy, respectively (P < .01). Mental
      demand, physical demand, temporal demand, performance, effort, and frustration
      were, respectively, scored 10.7 +/- 3.8, 11.7 +/- 3.5, 12.2 +/- 2.7, 11 +/- 3,
      13.6 +/- 2.7, and 13.5 +/- 2.8 in SILS and 6.3 +/- 3.1, 6.6 +/- 3.3, 7.3 +/- 3.3,
      7.1 +/- 4.1, 7.9 +/- 3.9, and 6.6 +/- 3.8 in standard laparoscopy (P < .01).
      CONCLUSIONS: SILS is mentally and physically demanding, particularly on arms and
      shoulders. Fatigue of big muscles, effort, and frustration were major challenges
      of SILS. Ergonomic intervention of instruments are needed to decrease mental and
      physical workload.

PMID- 25380605
TI  - Sir Gordon Gordon-Taylor (1878-1960), Anatomist and Surgeon: Surgical Innovations
      in the "Laboratory of War," His 1948 Lecture in Athens.

PMID- 25380606
TI  - What is the cost of quality for diabetes care?
AB  - Increasing the quality of care and reducing cost growth are core objectives of
      numerous private- and public-sector performance improvement initiatives. Using a
      unique panel data set for a commercially insured population and multivariate
      regression analysis, this study examines the relationship between medical care
      spending and diabetes-related quality measures, including provider-initiated
      processes of care and patient-dependent quality activities. Empirical evidence
      generated from this analysis of the relationship between a comprehensive set of
      diabetes quality measures and diabetes-related spending does not lend support for
      the assumption that high-quality preventive and primary care combined with
      effective patient self-management can lead to lower costs in the near term.
      Finally, we find no relationship between adjusted spending and intermediate
      clinical outcomes (e.g., HbA1c level) measured at the clinic level. 

PMID- 25380607
TI  - Social networks of professionals in health care organizations: a review.
AB  - In this article, we provide an overview of social network research in health
      care, with a focus on social interactions between professionals in organizations.
      We begin by introducing key concepts defining the social network approach,
      including network density, centrality, and brokerage. We then review past and
      current research on the antecedents of health care professionals' social networks
      including demographic attributes, professional groups, and organizational
      arrangements-and their consequences-including satisfaction at work, leadership,
      behaviors, knowledge transfer, diffusion of innovation, and performance. Finally,
      we examine future directions for social network research in health care, focusing
      on micro-macro linkages and network dynamics. 

PMID- 25380608
TI  - Examining the validity of AHRQ's patient safety indicators (PSIs): is variation
      in PSI composite score related to hospital organizational factors?
AB  - Increasing use of Agency for Healthcare Research and Quality's Patient Safety
      Indicators (PSIs) for hospital performance measurement intensifies the need to
      critically assess their validity. Our study examined the extent to which
      variation in PSI composite score is related to differences in hospital
      organizational structures or processes (i.e., criterion validity). In site visits
      to three Veterans Health Administration hospitals with high and three with low
      PSI composite scores ("low performers" and "high performers," respectively), we
      interviewed a cross-section of hospital staff. We then coded interview
      transcripts for evidence in 13 safety-related domains and assessed variation
      across high and low performers. Evidence of leadership and coordination of
      work/communication (organizational process domains) was predominantly favorable
      for high performers only. Evidence in the other domains was either mixed, or
      there were insufficient data to rate the domains. While we found some evidence of
      criterion validity, the extent to which variation in PSI rates is related to
      differences in hospitals' organizational structures/processes needs further
      study. 

PMID- 25380609
TI  - Impact of different etiologies of bronchiectasis on the pulmonary function tests.
AB  - BACKGROUND: Bronchiectasis develops along the natural course of several
      respiratory and systemic conditions and induces significant changes in the
      morphofunctional structure of airways. Our objective was to assess the impact of
      various causes of bronchiectasis on clinical data, pulmonary function tests, and
      high-resolution computed tomography (HRCT). METHODS: The present report was a
      cross-sectional study that was conducted with 112 consecutive patients with
      bronchiectasis, who were allocated to five groups, as follows: sequelae of
      tuberculosis, history of non-tuberculosis infection, cystic fibrosis (CF),
      primary ciliary dyskinesia (PCD), and rheumatoid arthritis. All of the
      participants underwent spirometry, whole-body plethysmography, measurement of the
      diffusing capacity for carbon monoxide (DLco), and HRCT. RESULTS: The highest
      HRCT score was exhibited in patients with CF (6.03 +/- 1.03). The values of
      forced expiratory volume in 1 second (FEV1) (52.2 +/- 17.7%) and DLco (74.1 +/-
      15.2%) were lower in patients with sequelae of tuberculosis. The increase in the
      residual volume was more accentuated in the patients with CF (193.5 +/- 39.5%)
      and PCD (189 +/- 36.4%). By the multivariate analysis, the cause of FEV1 and
      bronchiectasis, HRCT score, and degree of dyspnea behaved as independent
      predictors of DLco. CONCLUSION: In individuals with bronchiectasis, the pulmonary
      function abnormalities are associated with the etiology of the underlying
      disease.

PMID- 25380610
TI  - The emergent reversal of coagulopathies encountered in neurosurgery and
      neurology: a technical note.
AB  - It is imperative for neurologists, neurosurgeons, and neurointensivists to know
      how to stop life-threatening hemorrhage in both surgical and non-surgical
      patients. However, knowing how to medically correct a coagulopathy has become
      increasingly challenging as more contemporary and sophisticated anticoagulation
      agents are developed and prescribed. In a time-sensitive and life-threatening
      situation, where there is little margin for error, the neurosurgeon may not have
      ready access to information about the drug or condition that caused the
      coagulopathy or the information on how to treat it. This thorough review of the
      literature provides a comprehensive overview of the medications and conditions
      that can lead to persistent and/or life-threatening intracranial hemorrhage.

PMID- 25380611
TI  - Non-motor Factors Associated with the Attainment of Community Ambulation after
      Stroke.
AB  - OBJECTIVE: Detect the main predictive non-motor factors related to independent
      community ambulation after stroke. Furthermore, we propose a scale to estimate
      the probability of a stroke patient achieving independent community ambulation
      after 6 months of rehabilitation. DESIGN AND SETTINGS: Prospective cohort.
      Subjects treated in a rehabilitation center in a large metropolitan area.
      Independent community ambulation was evaluated after rehabilitation according to
      the Hoffer classification. Functional ambulation was assessed at four levels:
      nonambulatory, nonfunctional ambulation, household ambulation, and community
      ambulation. PARTICIPANTS: Patients (n=201) with a moderate disability after
      stroke. RESULTS: The average time of hospitalization was 19.3 days. However, only
      32.8% of the patients started the rehabilitation program during the first 6
      months after stroke. We found that 121 patients achieved community ambulation
      (60.2%), 40 achieved household ambulation (19.9%), 12 achieved therapeutic
      ambulation (5.9%), and 28 were non-ambulatory after 6 months of treatment. Based
      on our final model, a scoring scale was created in order to evaluate the
      probability of stroke patients achieving independent community ambulation after 6
      months of rehabilitation. Higher scores were associated with better chances of
      community ambulation within 6 months. CONCLUSIONS: The scale that evaluated these
      factors proved to have acceptable sensitivity and specificity to establish the
      prognosis of community ambulation after 6 months of rehabilitation.

PMID- 25380612
TI  - Extensive plexiform neurofibroma in a premature neonate.
AB  - We describe a premature neonate with an extensive plexiform neurofibroma.
      Prenatal ultrasound at 32 weeks of gestation was normal. Postnatal examination
      was significant for a palpable left neck mass. Magnetic resonance imaging (MRI)
      of the head demonstrated a mass involving the left cavernous sinus with spreading
      to the left orbital region. MRI of the neck was positive for extensive
      adenopathy, left more than right, with extension into the deep face region and
      infratemporal fossa on the left side. MRI of the chest, abdomen, and pelvis
      demonstrated a mass extending from the superior mediastinum to the left pelvic
      retroperitoneal region, including the mesenteric vasculature and spinal canal at
      multiple levels with compression of the spinal cord. Biopsy of the left neck mass
      confirmed for plexiform neurofibroma. A careful search of the literature revealed
      no previous report of such an extensive neurofibroma in a premature neonate.
      Surgical decompression in this premature neonate was not possible because of the
      extensive nature of the disease; it is known that neurofibroma is non-respondent
      to chemotherapy and radiotherapy. Therefore, alternative treatment is needed to
      improve the outcome.

PMID- 25380613
TI  - Cerebral venous thrombosis with subarachnoid hemorrhage: a case report.
AB  - Cerebral venous thrombosis (CVT) presenting as subarachnoid hemorrhage (SAH) is
      infrequent. We present the case of a man with CVT of the right transverse sinus
      who presented with a SAH in the right parietal sinus. In this case, we describe a
      hyper-homocysteinemia in a heterozygous patient for the methylenetetrahydrofolate
      reductase C667T mutation. Our report highlights the value of an early diagnosis
      of CVT, the importance of identifying possible causes that could be reversed with
      an appropriate treatment, and the controversy about the timing for starting
      anticoagulation therapy in such cases. 

PMID- 25380614
TI  - Improving Immunizations in Children: A Clinical Break-even Analysis.
AB  - INTRODUCTION: Immunizing the population is a vital public health priority. This
      article describes a resident-led continuous quality improvement project to
      improve the immunization rates of children under 3 years of age at two urban
      family medicine residency clinics in Salt Lake City, Utah, as well as a break
      even cost analysis to the clinics for the intervention. METHODS: Immunization
      records were distributed to provider-medical assistant teamlets daily for each
      pediatric patient scheduled in clinic to decrease missed opportunities. An
      outreach intervention by letter, followed by telephone call reminders, was
      conducted to reach children under 3 years of age who were behind on recommended
      immunizations for age (total n=457; those behind on immunizations n=101).
      Immunization rates were monitored at 3 months following start of intervention. A
      break-even analysis to the clinics for the outreach intervention was performed.
      RESULTS: Immunizations were improved from a baseline of 75.1% (n=133) and 79.6%
      (n=223) at the two clinics to 92.1% (n=163) and 89.6% (n=251), respectively, at 3
      months following the start of intervention (P<0.01). The average revenue per
      immunization given was $81.57. The financial break-even point required 36
      immunizations to be administered. CONCLUSION: Significant improvement in the
      immunization rate of patients under 3 years of age at two family medicine
      residency training clinics was achieved through decreasing missed opportunities
      for immunization in clinic, and with outreach through letters and follow-up phone
      calls. The intervention showed positive revenue to both clinics.

PMID- 25380615
TI  - Multiplexed modular genetic targeting of quantum dots.
AB  - While DNA-directed nanotechnology is now a well-established platform for
      bioinspired nanoscale assembly in vitro, the direct targeting of various
      nanomaterials in living biological systems remains a significant challenge.
      Hybrid biological systems with integrated and targeted nanomaterials may have
      interesting and exploitable properties, so methods for targeting various
      nanomaterials to precise biological locations are required. Fluorescence imaging
      has benefited from the use of nanoparticles with superior optical properties
      compared to fluorescent organic dyes or fluorescent proteins. While single
      particle tracking (SPT) in living cells with genetically encoded proteins is
      limited to very short trajectories, the high photon output of genetically
      targeted and multiplexed quantum dots (QDs) would enable long-trajectory analysis
      of multiple proteins. However, challenges with genetic targeting of QDs limit
      their application in these experiments. In this report, we establish a modular
      method for targeting QD nanoparticles selectively to multiple genetically encoded
      tags by precomplexing QD-streptavidin conjugates with cognate biotinylated hapten
      molecules. This approach enables labeling and SPT of multiple genetically encoded
      proteins on living cells at high speed and can label expressed proteins in the
      cytosol upon microinjection into living cells. While we demonstrate labeling with
      three distinct QD conjugates, the approach can be extended to other specific
      hapten-affinity molecule interactions and alternative nanoparticles, enabling
      precise directed targeting of nanoparticles in living biological systems. 

PMID- 25380616
TI  - Musculoskeletal sequelae in patients with obstetric fistula - a case-control
      study.
AB  - BACKGROUND: Obstetric fistula is essentially a result of pelvic injury caused by
      prolonged obstructed labour. Foot drop and walking difficulties in some of these
      women signify that the injury may extend beyond the loss of tissue that led to
      the fistula. However, these aspects of the pelvic injury are scarcely addressed
      in the literature. Here we specifically aimed at assessing musculoskeletal
      function in women with obstetric fistula to appreciate the extent of the sequelae
      of their pelvic injury. METHODS: This case-control study compared 70 patients
      with obstetric fistula with 100 controls matched for age and years since
      delivery. The following was recorded: height, weight, past and present walking
      difficulties, pain, muscle strength and joint range of motion, circumference and
      reflexes. Differences between groups were analysed using independent sample t
      test and chi-square test for independence. RESULTS: A history of leg pain was
      more common among cases compared to controls, 20% versus 7% (p = 0.02), and 29%
      of the cases had difficulties walking following the injuring delivery compared to
      none of the controls (p <= 0.001). Of these, four women reported spontaneous
      recovery. Cases had 7 degrees  less range of motion in ankle dorsal flexion
      (95%CI: -8.1, -4.8), 8 degrees  less ankle plantar flexion (95%CI: -10.6, -6.5),
      12 degrees  less knee flexion (95%CI: -14.1, -8.9), and 4 degrees  less knee
      extension (95%CI: 2.9, 5.0) compared to controls. Twelve % of the cases had lower
      ankle dorsal flexion strength (p = 0.009). Foot drop was present in three (4.3%)
      compared with none among controls. Women with fistula had 4 degrees  greater
      movement in hip extension (95%CI: -5.9, -3.1), 2 degrees  greater hip lateral
      rotation (95%CI: 0.7, 3.3) and 9 degrees  greater hip abduction (95%CI: 6.4,
      10.7). Twelve % of the cases had stronger medial rotation in the hip (p = 0.04),
      20% had stronger hip lateral rotation (p <= 0.001), 29% had stronger hip
      extension (p <= 0.001), and 15% had stronger hip abduction (p = 0.04) than
      controls. CONCLUSIONS: Women with obstetric fistula commonly experienced walking
      difficulties after the delivery, had often leg pain and reduced function in the
      ankle and knee joints that may have been compensated by increased motion and
      strength in the hip.

PMID- 25380617
TI  - Imaging features of adrenal ganglioneuroma: a case report.
AB  - BACKGROUND: Adrenal ganglioneuroma is a rare tumor constituting 20-30% of all
      ganglioneuromas. It is a benign tumor and can present diagnostic problems when
      confused with other adrenal solid tumors. CASE PRESENTATION: We herein report a
      case of adrenal ganglioneuroma in a 28-year-old Arabic patient and emphasize the
      diagnostic role of cross-sectional imaging modalities (computed tomography and
      magnetic resonance imaging). CONCLUSION: Imaging of adrenal ganglioneuromas is
      diagnostically challenging. Differentiation between adrenal ganglioneuroma and
      other solid adrenal tumors can be difficult. However, some suggestive features on
      computed tomography and magnetic resonance imaging are helpful in achieving a
      correct diagnosis.

PMID- 25380618
TI  - Hyperthermic intraperitoneal chemotherapy with oxaliplatin as treatment for
      peritoneal carcinomatosis arising from the appendix and pseudomyxoma peritonei: a
      survival analysis.
AB  - BACKGROUND: Appendiceal peritoneal carcinomatosis (PC) is rare and its long-term
      prognosis is poor. The aim of this study was to evaluate the results of an
      aggressive treatment approach used in our institution for the last eight years.
      METHODS: Data from all patients with PC arising from the appendix were
      prospectively collected and analyzed. Treatment consisted of complete surgical
      cytoreduction (CRS), followed by hyperthermic intraperitoneal chemotherapy
      (HIPEC) with oxaliplatin (460 mg/m2) at 43 degrees C over 30 minutes. Ronnett's
      histologic classification was used for tumor grading. RESULTS: Between February
      2003 and April 2011, 78 patients underwent laparotomy with curative intent. The
      mean follow-up period was 33.7 months. A total of 58 patients received HIPEC, but
      11 patients could not have CRS and received no HIPEC. Nine patients with a
      negative second-look surgery also received no HIPEC. The five-year overall
      survival for the entire cohort was 66.2%; 100% for the negative second-look
      patients, 77% for the HIPEC patients and 9% for the unresectable patients
      (P<0.0001). A total of 15 patients (25.9%) had isolated peritoneal recurrence, no
      patient had visceral recurrence only, and five patients (8.6%) had both. In
      regards to the five-year disease-free survival for the HIPEC patients, histologic
      grade (disseminated peritoneal adenomucinosis 100%, peritoneal mucinous
      carcinomatosis with intermediate features 40%, peritoneal mucinous carcinomatosis
      20%; p=0.0016) and completeness of cytoreduction (CCR-0 56%, CCR-1 24%; P=0.0172)
      were prognostic factors. There was one postoperative mortality. The major
      complication rate for patients treated with HIPEC was 40%, including intra
      abdominal abcess (17%), hemorrhage (12%) and anastomotic leak (10%). One patient
      in the HIPEC group experienced temporary grade II neuropathy and grade III
      thrombocytopenia. CONCLUSIONS: This therapeutic approach seems both feasible and
      safe in selected patients. Recurrence is, however, frequent and represents a
      challenge.

PMID- 25380619
TI  - ROCK1 as a novel prognostic marker in vulvar cancer.
AB  - BACKGROUND: Vulvar carcinoma is an infrequent tumour, accounting for fewer than
      3% of all malignant tumours that affect women, but its incidence is rising in the
      past few decades. In young women, the manifestation of the vulvar carcinoma is
      often linked to risk factors such as smoking and HPV infection, but most cases
      develop in women aged over 50 years through poorly understood genetic mechanisms.
      Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) has been
      implicated in many cellular processes, but its function in vulvar cancer has
      never been examined. In this study, we aimed to determine the prognostic value of
      ROCK1 gene and protein analysis in vulvar squamous cell carcinoma (VSCC).
      METHODS: ROCK1 expression levels were measured in 16 vulvar tumour samples and
      adjacent normal tissue by qRT-PCR. Further, 96 VSCC samples were examined by
      immunohistochemistry (IHC) to confirm the involvement of ROCK1 in the disease.
      The molecular and pathological results were correlated with the clinical data of
      the patients. Sixteen fresh VSCC samples were analyzed by array-based comparative
      genomic hybridization (aCGH). RESULTS: In each pair of samples, ROCK1 levels were
      higher by qRT-PCR in normal tissue compared with the tumour samples (p = 0.016).
      By IHC, 100% of invasive front areas of the tumour and 95.8% of central tumour
      areas were positive for ROCK1. Greater expression of ROCK1 was associated with
      the absence of lymph node metastasis (p = 0.022) and a lower depth of invasion (p
      = 0.002). In addition, higher ROCK1 levels correlated with greater recurrence
      free survival (p = 0.001). Loss of ROCK1 was independently linked to worse cancer
      specific survival (p = 0.0054) by multivariate analysis. This finding was
      validated by IHC, which demonstrated enhanced protein expression in normal versus
      tumour tissue (p < 0.001). By aCGH, 42.9% of samples showed a gain in copy number
      of the ROCK1 gene. CONCLUSIONS: ROCK1 is lower expressed in tumour tissue when
      compared with adjacent normal vulvar epithelia. In an independent sample set of
      VSCCs, lower expression levels of ROCK1 correlated with worse survival rates and
      a poor prognosis. These findings provide important information for the clinical
      management of vulvar cancer.

PMID- 25380620
TI  - Profiling gene promoter occupancy of Sox2 in two phenotypically distinct breast
      cancer cell subsets using chromatin immunoprecipitation and genome-wide promoter
      microarrays.
AB  - INTRODUCTION: Aberrant expression of the embryonic stem cell marker Sox2 has been
      reported in breast cancer (BC). We previously identified two phenotypically
      distinct BC cell subsets separated based on their differential response to a Sox2
      transcription activity reporter, namely the reporter-unresponsive (RU) and the
      more tumorigenic reporter-responsive (RR) cells. We hypothesized that Sox2, as a
      transcription factor, contributes to their phenotypic differences by mediating
      differential gene expression in these two cell subsets. METHODS: We used
      chromatin immunoprecipitation and a human genome-wide promoter microarray (ChIP
      chip) to determine the promoter occupancies of Sox2 in the MCF7 RU and RR breast
      cancer cell populations. We validated our findings with conventional chromatin
      immunoprecipitation, quantitative reverse transcription polymerase chain reaction
      (qPCR), and western blotting using cell lines, and also performed qPCR using
      patient RU and RR samples. RESULTS: We found a largely mutually exclusive profile
      of gene promoters bound by Sox2 between RU and RR cells derived from MCF7 (1830
      and 456 genes, respectively, with only 62 overlapping genes). Sox2 was bound to
      stem cell- and cancer-associated genes in RR cells. Using quantitative RT-PCR, we
      confirmed that 15 such genes, including PROM1 (CD133), BMI1, GPR49 (LGR5), and
      MUC15, were expressed significantly higher in RR cells. Using siRNA knockdown or
      enforced expression of Sox2, we found that Sox2 directly contributes to the
      higher expression of these genes in RR cells. Mucin-15, a novel Sox2 downstream
      target in BC, contributes to the mammosphere formation of BC cells. Parallel
      findings were observed in the RU and RR cells derived from patient samples.
      CONCLUSIONS: In conclusion, our data supports the model that the Sox2 induces
      differential gene expression in the two distinct cell subsets in BC, and
      contributes to their phenotypic differences.

PMID- 25380621
TI  - Effect of Nigella sativa on immune response in treadmill exercised rat.
AB  - BACKGROUND: In the present study the effect of Nigella sativa (N. sativa)
      ethanolic extract on cytokine profile in control, moderate and overtrained heavy
      exercised rat was examined. METHODS: Male Wistar rats were randomly divided into
      control sedentary (C), moderate trained (MT), (V = 20 m/min, 30 min/day, 6 days a
      week, for 8 weeks), overtrained (OT) (V = 25 m/min, 60 min/day, 6 days a week,
      for 11 weeks), control sedentary + N. sativa (NC), moderate trained + N. sativa
      (NM) and overtrained + N. sativa (NO). Immediately and 24 h after the last bout
      of exercise blood samples were obtained. The serum concentrations of TNFalpha, IL
      6, IL-10, IL-4 and IFNgamma were measured by ELISA method. RESULTS: Immediately
      after exercise the following findings were observed; IL-6, IL-10 and TNFalpha
      concentration increased in OT and NC groups but Just IL-6 in MT groups compared
      with control (P< 0.05-P< 0.001). Serum level of IL-4 decreased in MT and NC (P<
      0.05-P< 0.001) but IFNgamma increased (P< 0.05) just in MT group vs control. In
      addition, circulatory levels of TNFalpha, IL-6, IL-10 and IL-4 were higher in OT
      and NM groups but the IFNgamma concentration was lower in the OT group than the
      MT group (P< 0.05-P< 0.01). The IFN-gamma/IL4 ratio was significantly increased
      in MT and NC (P< 0.05-P< 0.01) while it decreased in OT group. There were not
      statistical differences in TNFalpha, IL-6, and IFNgamma levels between different
      time intervals after exercise in all groups. CONCLUSIONS: Chronic administration
      of N. sativa may change pro and anti-inflammatory cytokines profiles. Also it may
      act as a balancing factor on Th1/Th2 lymphocytes in different exercise loads and
      act as an inhibitory factor on Th2 phenotype in control animals.

PMID- 25380622
TI  - Normative data for the Montreal Cognitive Assessment in an Italian population
      sample.
AB  - The Montreal Cognitive Assessment (MoCA) is a rapid screening battery, also
      including subtests to assess frontal functions such as set-shifting, abstraction
      and cognitive flexibility. MoCA seems to be useful to identify non-amnestic mild
      cognitive impairment (MCI) and subcortical dementia; it has high sensitivity and
      specificity in distinguishing MCI from mild Alzheimer's Disease. Previous studies
      revealed that certain items of MoCA may be culturally biased and highlighted the
      need for population-based norms for the MoCA. The aim of present study was to
      collect normative values in a sample of Italian healthy subjects. Four hundred
      and fifteen Italian healthy subjects (252 women and 163 men) of different ages
      (age range 21-95 years) and educational level (from primary to university)
      underwent MoCA and Mini Mental State Examination (MMSE). Multiple linear
      regression analysis revealed that age and education significantly influenced
      performance on MoCA. No significant effect of gender was found. From the derived
      linear equation, a correction grid for MoCA raw scores was built. Inferential cut
      off score, estimated using a non-parametric technique, is 15.5 and equivalent
      scores were computed. Correlation analysis showed a significant but weak
      correlation between MoCA adjusted scores with MMSE adjusted scores (r = 0.43, p <
      0.001). The present study provided normative data for the MoCA in an Italian
      population useful for both clinical and research purposes.

PMID- 25380623
TI  - The beta-amyloid precursor protein analog P165 improves impaired insulin signal
      transduction in type 2 diabetic rats.
AB  - This study was performed to understand whether P165 improves learning and memory
      by restoring insulin action using a diabetes mellitus (DM) rat model. A total of
      34 male Sprague-Dawley rats were randomly divided into four groups: control group
      (n = 8), DM group (n = 8), DM group treated with a low dose of P165 (n = 9), and
      DM group treated with a high dose of P165 (n = 9). After 8 weeks of treatment,
      the animals were killed and the expression of insulin signaling-related proteins
      was examined in the hippocampus by Western blot and immunohistochemical staining.
      Administration of P165 in diabetic rats did not induce a significant effect on
      the fasting blood glucose level. The expression of IR, IRS-1, AKT, p-CREB, and
      Bcl-2 proteins was significantly enhanced in the hippocampus in diabetic rats.
      Treatment of diabetic rats with P165 at both low and high doses significantly
      attenuated the expression levels of these proteins. Moreover,
      immunohistochemistry staining showed that IR, IRS-1, AKT, p-CREB, and Bcl-2 were
      abundantly expressed in the CA1 region of the hippocampus. The number of cells
      positively stained for the above proteins was significantly higher in diabetic
      tissues compared to control tissues, whereas P165 treatments induced a
      significant reduction in the expression of these proteins. The expression of IR,
      IRS-1, AKT, p-CREB, and Bcl-2 was enhanced in DM rats, and administration of P165
      normalized the expression of these molecules, suggesting that P165 can improve
      impaired insulin signal transduction.

PMID- 25380624
TI  - Effect of negative emotions evoked by light, noise and taste on trigeminal
      thermal sensitivity.
AB  - BACKGROUND: Patients with migraine often have impaired somatosensory function and
      experience headache attacks triggered by exogenous stimulus, such as light, sound
      or taste. This study aimed to assess the influence of three controlled
      conditioning stimuli (visual, auditory and gustatory stimuli and combined
      stimuli) on affective state and thermal sensitivity in healthy human
      participants. METHODS: All participants attended four experimental sessions with
      visual, auditory and gustatory conditioning stimuli and combination of all
      stimuli, in a randomized sequence. In each session, the somatosensory sensitivity
      was tested in the perioral region with use of thermal stimuli with and without
      the conditioning stimuli. Positive and Negative Affect States (PANAS) were
      assessed before and after the tests. Subject based ratings of the conditioning
      and test stimuli in addition to skin temperature and heart rate as indicators of
      arousal responses were collected in real time during the tests. RESULTS: The
      three conditioning stimuli all induced significant increases in negative PANAS
      scores (paired t-test, P <=0.016). Compared with baseline, the increases were in
      a near dose-dependent manner during visual and auditory conditioning stimulation.
      No significant effects of any single conditioning stimuli were observed on
      trigeminal thermal sensitivity (P >=0.051) or arousal parameters (P >=0.057). The
      effects of combined conditioning stimuli on subjective ratings (P <=0.038) and
      negative affect (P = 0.011) were stronger than those of single stimuli.
      CONCLUSIONS: All three conditioning stimuli provided a simple way to evoke a
      negative affective state without physical arousal or influence on trigeminal
      thermal sensitivity. Multisensory conditioning had stronger effects but also
      failed to modulate thermal sensitivity, suggesting that so-called exogenous
      trigger stimuli e.g. bright light, noise, unpleasant taste in patients with
      migraine may require a predisposed or sensitized nervous system.

PMID- 25380625
TI  - Circulating levels of apelin, glucagon-like peptide and visfatin in
      hypercholesterolemic-hyperhomocysteinemic guinea-pigs: their relation with NO
      metabolism.
AB  - The aim of this study was to determine the levels of regulatory peptides apelin,
      glucagon-like peptide (GLP-1) and visfatin in hypercholesterolemic and
      hyperhomocysteinemic state and to examine their relation with nitric oxide (NO)
      metabolism. 32 Male guinea pigs were divided into four groups and each group was
      fed as follows: (a) commercial chow, (b) cholesterol (chol)-rich diet, (c)
      methionine (meth)-rich diet, and (d) chol + meth-rich diet. Blood samples were
      drawn at the end of 10 weeks, and abdominal aorta was dissected for
      histopathological examination. Serum insulin, GLP-1, apelin, visfatin, and
      nitrotyrosine concentrations were measured by the manufacturer's kits based on
      ELISA; asymmetric dimethylarginine (ADMA) and arginine levels were measured by
      the high performance liquid chromatography. Homocysteine level was measured by
      the chemiluminescence immunoassay; glucose, total chol and triglyceride levels
      were measured by the autoanalyzer. The microscopic examination of aorta indicated
      varying degrees of vascular disturbance in chol- and chol + meth-fed groups. High
      levels of chol and homocysteine, accompanied with significantly low levels of
      apelin and GLP-1 were detected in the plasma. Visfatin, ADMA, and nitrotyrosine
      levels both in chol- and chol + meth-fed groups were significantly higher than
      those in control animals, whereas arginine and arginine/ADMA ratio were lower.
      This study indicated that circulating levels of apelin, GLP-1, and visfatin are
      markedly altered during the development of atherosclerotic changes in close
      association with chol, homocysteine, NO, and ADMA levels. The measurements of
      these peptides in serum may help for the diagnosis and follow-up of vascular
      dysfunction.

PMID- 25380626
TI  - Antimicrobial peptide GW-H1-induced apoptosis of human gastric cancer AGS cell
      line is enhanced by suppression of autophagy.
AB  - Gastric cancer is one of the most common malignant cancers worldwide. Due to its
      poor prognosis and high mortality rate, development of an effective therapeutic
      method is of urgent need. It has been reported that antimicrobial peptides
      (AMPs), also known as host-defense peptides, can selectively bind to negatively
      charged prokaryotic and cancer cell membranes and exert cytotoxicity, without
      harming normal cells or causing severe drug resistance. We have designed a series
      of novel cationic AMPs with potent antimicrobial activity against a broad
      spectrum of bacterial pathogens. In the current study, we evaluated their
      anticancer potency toward gastric cancer AGS cell line. Cell viability assay
      revealed that GW-H1 exhibited the lowest IC50 value (less than 20 MUM). Flow
      cytometry showed that upon GW-H1 treatment for 0-24 h, apoptotic cell populations
      of AGS increased in a dose- and time-dependent manner. Western blot analysis
      further revealed that upon treatment for 2-6 h, apoptosis-related caspases-3, 7,
      8, 9, and PARP were cleaved and activated, while autophagy-related LC3-II and
      beclin-1 were concomitantly increased. These results indicated that both
      apoptosis and autophagy were involved in the early stage of GW-H1-induced AGS
      cell death. However, upon treatment for 12-24 h, LC3-II began to decrease and
      cleaved beclin-1 increased in a time-dependent manner, suggesting that
      consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus
      enhancing apoptosis at the final stage. These findings provided support for
      future application of GW-H1 as a potential anticancer agent for gastric cancer
      treatment.

PMID- 25380627
TI  - Role of GPR120 in cell motile activity induced by 12-O-tetradecanoylphorbol-13
      acetate in liver epithelial WB-F344 cells.
AB  - G-protein-coupled receptor 120 (GPR120) is identified as a G-protein-coupled
      receptor for unsaturated long-chain free fatty acids that mediates insulin
      signaling and anti-inflammatory effects. Recently, it has been reported that
      GPR120 promotes the cell motile activity and angiogenesis in cancer cells. In
      this study, we assessed the role of GPR120 in the cell motile activity induced by
      12-O-tetradecanoylphorbol-13-acetate (TPA) in rat liver epithelial WB-F344 cells.
      Cells were treated with TPA at a concentration of 5 nM for 72 h. The expression
      level of the Gpr120 gene was measured by quantitative real-time RT-PCR analysis.
      Cells treated with TPA showed the elevated Gpr120 expression, in comparison with
      untreated cells. In cell motility assays, the cell motile activity of cells
      treated with TPA was significantly higher than that of untreated cells. To
      confirm whether GPR120 is involved in the cell motile activity mediated by TPA,
      we generated GPR120 knockdown cells from WB-F344 cells. The cell motile activity
      induced by TPA was significantly suppressed by GPR120 knockdown. These results
      suggest that GPR120 plays an important role in the cell motile activity induced
      by TPA in WB-F344 cells.

PMID- 25380628
TI  - Nonlinear mixed effects modelling approach in investigating phenobarbital
      pharmacokinetic interactions in epileptic patients.
AB  - PURPOSE: The present study aimed to establish population pharmacokinetic model
      for phenobarbital (PB), examining and quantifying the magnitude of PB
      interactions with other antiepileptic drugs concomitantly used and to demonstrate
      its use for individualization of PB dosing regimen in adult epileptic patients.
      METHODS: In total 205 PB concentrations were obtained during routine clinical
      monitoring of 136 adult epilepsy patients. PB steady state concentrations were
      measured by homogeneous enzyme immunoassay. Nonlinear mixed effects modelling
      (NONMEM) was applied for data analyses and evaluation of the final model.
      RESULTS: According to the final population model, significant determinant of
      apparent PB clearance (CL/F) was daily dose of concomitantly given valproic acid
      (VPA). Typical value of PB CL/F for final model was estimated at 0.314 l/h. Based
      on the final model, co-therapy with usual VPA dose of 1000 mg/day, resulted in PB
      CL/F average decrease of about 25 %, while 2000 mg/day leads to an average 50 %
      decrease in PB CL/F. CONCLUSIONS: Developed population PB model may be used in
      estimating individual CL/F for adult epileptic patients and could be applied for
      individualizing dosing regimen taking into account dose-dependent effect of
      concomitantly given VPA.

PMID- 25380630
TI  - Assessment of bioaerosol pollution over Indo-Gangetic plain.
AB  - Aerosol plays a very important role in climate change and public health. It
      affects cloud condensation nuclei and causes a number of epidemic diseases. The
      correlations of aerosol with epidemic diseases are due to the biotic components
      of aerosol. The present study deals with the measurements and characterization of
      bioaerosol over Indo-Gangetic plain. The levels of PM10 and PM2.5 are much higher
      than the recommended value set by NAAQS in India. Bacterial and fungal
      concentrations are in the reported range. Bacterial concentration is higher than
      fungal concentration. Gram-positive bacteria contribute 75% while gram-negative
      bacteria contribute 25% only. A total seven types of fungi are identified in
      aerosols. Aspergillus niger is dominant. Meteorological parameters play important
      roles in growth and presence of microorganism in the air. Bacterial
      concentrations are governed mainly by temperature while fungal concentration is
      influenced by relative humidity.

PMID- 25380631
TI  - Assessment of metal contamination in water, sediment, and tissues of Arius
      thalassinus fish from the Red Sea coast of Yemen and the potential human risk
      assessment.
AB  - Heavy metal pollution is one of the most serious environmental issues globally.
      To evaluate the metal pollution in the Red Sea coast of Hodeida, Yemen Republic,
      the concentrations of Fe, Cu, Ni, Pb, and Cd in water, sediment, and some vital
      organs of sea catfish, Arius thalassinus collected from polluted and unpolluted
      sites, were determined. The risk of these metals to humans through fish
      consumption was then assessed. The results showed that the concentration order of
      metals in water, sediment, and fish tissues were Fe > Cu > Ni > Pb > Cd. The
      levels of studied metals in water, sediment, and fish tissues were significantly
      higher in the polluted site than those of the unpolluted site, with few
      exceptions. Linear correlation incorporating paired variables (water-sediment,
      water-fish, and fish-fish) exhibited several significant correlations indicating
      a common metal pollution. The risk assessment performed revealed that fish
      consumption was safe for consumers. This field investigation provides a baseline
      data on metal pollution in this region. 

PMID- 25380629
TI  - Optimizing elderly pharmacotherapy: polypharmacy vs. undertreatment. Are these
      two concepts related?
AB  - PURPOSE: This study aimed to estimate the prevalence of polypharmacy and
      potential prescribing omissions (PPO) and their related factors in community
      dwelling elderly patients and to examine any possible relationship between these
      two concepts. METHODS: A cross-sectional study was carried out including patients
      65 years of age or over living on the island of Lanzarote (Spain).
      Sociodemographic, clinical and functional variables were collected, together with
      full data on drug therapy. The percentage of patients receiving >=5 medications
      (polypharmacy) and the percentage of patients receiving at least one PPO
      according to Screening Tool to Alert doctors to Right Treatment (START) criteria
      (underprescription) were the two primary endpoints. RESULTS: A total of 1844
      medications were prescribed to the 407 patients included in our study. The
      overall prevalence of polypharmacy was 45 %. The risk factors associated with
      polypharmacy were comorbidity (OR 1.98, 95 % CI 1.63-2.44), limitations in
      activities of daily living (ADL; OR 3.0, 95 % CI 1.51-6.11), and being prescribed
      a drug in the Anatomical Therapeutic Chemical classification (ATC) C group (OR
      7.92, 95 % CI 4.10-16.25) or in the N group (OR 3.80, 95 % CI 2.25-6.55). START
      criteria identified a total of 303 PPO in 170 (41.8 %) subjects. The risk of PPO
      increased by 60 % for every additional point in the Charlson Comorbidity Index
      (OR 1.60, 95 % CI 1.35-1.91). Polypharmacy also independently predicted the odds
      of at least one PPO according to START criteria (OR 2.19, 95 % CI 1.36-3.55).
      CONCLUSION: Our findings show high rates of polypharmacy and PPO, as well as a
      clear relationship between these two concepts.

PMID- 25380632
TI  - Membrane-integrated physico-chemical treatment of coke-oven wastewater: transport
      modelling and economic evaluation.
AB  - A modelling and simulation study with economic evaluation was carried out for an
      advanced membrane-integrated hybrid treatment process that ensures reuse of water
      with recovery of ammoniacal nitrogen as struvite from coke-oven wastewater.
      Linearized transport model was developed based on extended Nernst-Plank and
      concentration polarization modulus equation. Effects of pH, transmembrane
      pressure and cross-flow rate of interest on membrane charge density, solute
      rejection and solvent flux were investigated. The membrane module was successful
      in yielding a pure water flux as high as 120 L m(-2) h(-1) removing more than 95
      and 96% of the cyanide and phenol, respectively, while permeating more than 90%
      NH4 (+)-N at a transmembrane pressure of only 15 * 10(2) KPa and at a pH of 10
      for a volumetric cross-flow rate of 800 L h(-1). The Fenton's reagents were used
      to degrade more than 99% of pollutants present in the concentrated stream. The
      developed model could successfully predict the plant performance as reflected in
      the very low relative error (0.01-0.12) and overall high correlation coefficient
      (R(2) > 0.96). Economic analysis indicated that such a membrane-integrated hybrid
      system could be quite promising in coke wastewater treatment at low cost i.e.
      $0.934/m(2) of wastewater.

PMID- 25380633
TI  - Diversity of acidophilic prokaryotes at two acid mine drainage sites in Turkey.
AB  - The biodiversity of acidophilic prokaryotes in two acidic (pH 2.8-3.05) mine
      drainage (AMD) sites (Balya and Can) in Turkey was examined using a combined
      cultivation-based and cultivation-independent approach. The latter included
      analyzing microbial diversity using fluorescent in situ hybridization (FISH),
      terminal restriction enzyme fragment length polymorphism ('T-RFLP), and
      quantitative PCR (qPCR). Numbers of cultivatable heterotrophic acidophilic
      bacteria were over an order of magnitude greater than those of chemolithotrophic
      acidophiles in both AMD ponds examined. Isolates identified as strains of
      Acidithiobacillus ferrivorans, Acidiphilium organovorum, and Ferrimicrobium
      acidiphilum were isolated from the Balya AMD pond, and others identified as
      strains of Leptospirillum ferriphilum, Acidicapsa ligni, and Acidiphilium rubrum
      from Can AMD. Other isolates were too distantly related (from analysis of their
      16S rRNA genes) to be identified at the species level. Archaeal diversity in the
      two ponds appeared to be far more limited. T-RFLP and qPCR confirmed the presence
      of Ferroplasma-like prokaryotes, but no archaea were isolated from the two sites.
      qPCR generated semiquantitative data for genera of some of the iron-oxidizing
      acidophiles isolated and/or detected, suggesting the order of abundance was
      Leptospirillum > Ferroplasma > Acidithiobacillus (Balya AMD) and Ferroplasma >
      Leptospirillum > Acidithiobacillus (Can AMD).

PMID- 25380634
TI  - Daily social enjoyment interrupts the cycle of same-day and next-day fatigue in
      women with fibromyalgia.
AB  - BACKGROUND: Fatigue is a debilitating symptom of fibromyalgia (FM) that has
      limited treatment options. Some evidence, however, has linked positive social
      engagement with reduced within-day fatigue. PURPOSE: This study elaborated
      longitudinal within-day and across-day relations between FM fatigue and social
      enjoyment. METHODS: One hundred seventy-six women with FM completed 21-day
      automated diaries assessing morning and end-of-day fatigue, and both afternoon
      social enjoyment and stress within two social domains: non-spousal and spousal.
      RESULTS: In the non-spousal domain, analysis supported a mediational path from
      lower morning fatigue to higher afternoon social enjoyment, which predicted lower
      end-of-day fatigue, and subsequently, lower next-morning fatigue. Enjoyment
      exerted a greater impact on within-day fatigue than did stress. Patterns in the
      spousal domain were similar, but the mediated path was nonsignificant.
      CONCLUSIONS: Positive social engagement offers relief from FM fatigue that
      carries over across days and may provide an additional target to enhance the
      effectiveness of current interventions.

PMID- 25380635
TI  - A phase I pharmacokinetic and safety analysis of epothilone folate (BMS-753493),
      a folate receptor targeted chemotherapeutic agent in humans with advanced solid
      tumors.
AB  - Background The folate receptor alpha is selectively over-expressed in a number of
      human cancers. BMS-753493 is a folate conjugate of the epothilone analog BMS
      748285 that was designed to selectively target folate receptor expressing cancer
      cells. Methods BMS-753493 was investigated in two parallel multi-institutional
      first-in-human phase I/IIa studies in patients with advanced solid tumors. In
      Study 1, patients were treated on a schedule of once daily dosing of BMS-753493
      administered on Days 1, 4, 8 and 11 every 21 days with a starting dose of 5 mg
      daily and in Study 2, patients were treated once daily on Days 1-4 every 21 days,
      with a starting dose of 2.5 mg daily. Results A total of 65 patients were treated
      across the two studies. The maximum tolerated dose (MTD) was 26 mg in Study 1 and
      15 mg in Study 2. Fatigue, transaminitis, gastrointestinal toxicity, and
      mucositis were dose-limiting toxicities. One patient in Study 2 developed Stevens
      Johnson syndrome attributed to BMS-753493. Plasma exposures of both the
      conjugated and free epothilone increased in a dose related fashion in both
      studies and the half-life of the conjugated epothilone was 0.2-0.6 h across dose
      levels. No objective tumor responses were seen in either study. Conclusions BMS
      753493 was generally tolerable and toxicities known to be associated with
      epothilone class of anticancer agents were common, although peripheral neuropathy
      and neutropenia appear to have been less frequent and less severe as compared to
      epothilones. Antitumor activity was not demonstrated and further development of
      BMS-753493 has been discontinued.

PMID- 25380636
TI  - A phase I study of farletuzumab, a humanized anti-folate receptor alpha
      monoclonal antibody, in patients with solid tumors.
AB  - Farletuzumab is a humanized monoclonal antibody against folate receptor alpha
      (FRA). The purpose of the study is to assess safety and tolerability, the
      pharmacokinetic (PK) profile, and preliminary antitumor effect. Patients with
      ovarian cancer (OC) or FRA-expressing solid tumors who are resistant to standard
      treatments were eligible for the study. After single-dose administration for PK
      assessment, farletuzumab was administered by intravenous injection, repeating
      every week until disease progression. Dose-limiting toxicities (DLTs) were
      defined as grade 4 hematological and grade 3/4 nonhematological toxicities. Dose
      escalation was planned in 4 cohorts (50, 100, 200, and 400 mg/m(2)). Fourteen
      patients with OC and two patients with gastric cancer (GC) received farletuzumab
      infusion. Neither DLTs nor grade 3/4 toxicities were reported in all cohorts.
      Major adverse events, including grade 1/2 infusion related reaction (15 patients,
      93.8%), headache (seven patients, 43.8%), and nausea and decreased appetite (five
      patients each, 31.3%), were observed and medically managed. AUC and Cmax
      increased dose-dependently and linear PK profiles were observed. No tumor
      shrinkage was recorded, but long-term disease stabilization for 25 and 20 months
      was observed in one patient with clear cell OC (100 mg/m(2)) and one patient with
      GC (400 mg/m(2)), respectively. No cumulative toxicity occurred in any patient.
      Farletuzumab was well tolerated in Japanese patients with a similar PK profile as
      compared with the US population. Long-term disease stabilization was observed in
      a subpopulation of clear cell OC and GC; both of them were resistant and
      progressive after standard chemotherapies (ClinicalTrials.gov Identifier:
      NCT01049061).

PMID- 25380637
TI  - Dendritic morphology predicts pattern recognition performance in multi
      compartmental model neurons with and without active conductances.
AB  - In this paper we examine how a neuron's dendritic morphology can affect its
      pattern recognition performance. We use two different algorithms to
      systematically explore the space of dendritic morphologies: an algorithm that
      generates all possible dendritic trees with 22 terminal points, and one that
      creates representative samples of trees with 128 terminal points. Based on these
      trees, we construct multi-compartmental models. To assess the performance of the
      resulting neuronal models, we quantify their ability to discriminate learnt and
      novel input patterns. We find that the dendritic morphology does have a
      considerable effect on pattern recognition performance and that the neuronal
      performance is inversely correlated with the mean depth of the dendritic tree.
      The results also reveal that the asymmetry index of the dendritic tree does not
      correlate with the performance for the full range of tree morphologies. The
      performance of neurons with dendritic tapering is best predicted by the mean and
      variance of the electrotonic distance of their synapses to the soma. All
      relationships found for passive neuron models also hold, even in more accentuated
      form, for neurons with active membranes. 

PMID- 25380638
TI  - Comparing willingness to pay for improved drinking-water quality using stated
      preference methods in rural and urban Kenya.
AB  - BACKGROUND: Access to safe drinking water has been on the global agenda for
      decades. The key to safe drinking water is found in household water treatment and
      safe storage systems. OBJECTIVE: In this study, we assessed rural and urban
      household demand for a new gravity-driven membrane (GDM) drinking-water filter.
      METHODS: A choice experiment (CE) was used to assess the value attached to the
      characteristics of a new GDM filter before marketing in urban and rural Kenya.
      The CE was followed by a contingent valuation (CV) question. Differences in
      willingness to pay (WTP) for the same filter design were tested between methods,
      as well as urban and rural samples. RESULTS: The CV follow-up approach produces
      more conservative and statistically more efficient WTP values than the CE, with
      only limited indications of anchoring. The effect of the new filter technology on
      children with diarrhea is among the most important drivers behind choice behavior
      and WTP in both areas. The urban sample is willing to pay more in absolute terms
      than the rural sample irrespective of the valuation method. Rural households are
      more price sensitive, and willing to pay more in relative terms compared with
      disposable household income. CONCLUSION: A differentiated marketing strategy
      across rural and urban areas is expected to increase uptake and diffusion of the
      new filter technology.

PMID- 25380639
TI  - Microwave-mediated extracellular synthesis of metallic silver and zinc oxide
      nanoparticles using macro-algae (Gracilaria edulis) extracts and its anticancer
      activity against human PC3 cell lines.
AB  - A rapid and novel microwave-mediated protocol was established for extracellular
      synthesis of metallic silver (Ag) and zinc oxide (ZnO) nanoparticles using the
      extracts of macro-algae Gracilaria edulis (GE) and also examined its anticancer
      activity against human prostate cancer cell lines (PC3). The formation of silver
      nanoparticles (GEAgNPs) and zinc oxide nanoparticles (GEZnONPs) in the reaction
      mixture was determined by ultraviolet-visible spectroscopy. The synthesized Ag
      and ZnO nanoparticles were characterized by X-ray diffraction, Fourier transform
      infra-red spectroscopy, energy dispersive X-ray, and field emission scanning
      electron microscopy. The silver and zinc oxide nanoparticles were spherical and
      rod-shaped, respectively. Cell viability assays were carried out to determine the
      cytotoxic effects of AgNPs and ZnONPs against PC3 and normal African monkey
      kidney (VERO) cell line. The inhibitory concentration values were found to be
      39.60, 28.55, 53.99 MUg/mL and 68.49, 88.05, 71.98 MUg/mL against PC3 cells and
      Vero cells for AgNPs, ZnONPs, and aqueous G. edulis extracts, respectively, at 48
      h incubation period. As evidenced by acridine orange/ethidium bromide staining,
      the percentage of the apoptotic bodies was found to be 62 and 70 % for AgNPs and
      ZnONPs, respectively. The present results strongly suggest that the synthesized
      ZnONPs showed an effective anticancer activity against PC3 cell lines than AgNPs.

PMID- 25380640
TI  - The effect of heavy metal-induced oxidative stress on the enzymes in white rot
      fungus Phanerochaete chrysosporium.
AB  - Prevalence of heavy metals in the living environment causes chemical stress and
      reactive oxygen species (ROS) formation in Phanerochaete chrysosporium (P.
      chrysosporium). However, the mechanisms involved in ROS defense are still under
      investigation. In the present study, we evaluated the effect of lead- and cadmium
      induced oxidative stress on the activities of catalase (CAT), peroxidase (POD),
      lignin peroxidase (LiP), and manganese peroxidase (MnP). A time-dependent change
      in all enzyme activities was observed following exposure to 50 MUM cadmium and 25
      MUM lead. The lowest values were recorded at 4 h after exposure. Both cadmium and
      lead inhibited CAT and POD. The cytochrome P450 (CYP450) levels increased under
      50-100 MUM cadmium or lead exposure and decreased when heavy metal concentration
      was under 50 MUM; this suggested that ROS is not the only factor that alters the
      CYP450 levels. The cadmium removal rate in the sample containing 900 MUM
      taxifolin (inhibitor of CYP450) and 100 MUM cadmium was reduced to 12.34 %, 9.73
      % lower than that of 100 MUM cadmium-induced sample, indicating CYP450 may play
      an indirect but key role in the process of clearance of heavy metals. The pH of
      the substrate solution decreased steadily during the incubation process.

PMID- 25380641
TI  - In vitro alpha-glucosidase inhibition, antioxidant, anticancer, and
      antimycobacterial properties of ethyl acetate extract of Aegle tamilnadensis
      Abdul Kader (Rutaceae) leaf.
AB  - The present study was aimed to investigate in vitro alpha-glucosidase inhibition,
      antioxidant, anticancer, and antimycobacterial activities of the ethyl acetate
      extract of A. tamilnadensis leaves. The extract recorded strong alpha-glucosidase
      inhibition with an IC50 value of 100 MUg/ml. The antioxidant potential of the
      extract was evaluated by nitric oxide radical inhibition, lipid peroxidation
      inhibition, ferric thiocyanate, and ABTS radical scavenging assay, and the
      extract recorded significant antioxidant activity. The ferric thiocyanate
      activity of extract was superior to butylated hydroxyl anisol (BHA), the standard
      antioxidant agent. The anticancer activity of the extract was evaluated against
      (1) breast cancer cell lines (MDAM B-231), (2) cervical cancer cell lines (HeLa),
      and (3) lung cancer cell line (A 549) using MTT assay, and significant activity
      was recorded against A 549 with an IC50 value of 64 MUg/ml. Further studies on
      the morphology, acridine orange/ethidium bromide staining, and cell cycle
      analysis by flow cytometry confirm the extract-induced apoptosis in A 549. This
      extract also recorded significant anti-tuberculosis activity against
      Mycobacterium smegmatis. The current study suggests that the ethyl acetate
      extract of A. tamilnadensis is a potential source of natural alpha-glucosidase
      inhibitor and antioxidant for protection as well as prevention of life
      threatening diseases like cancer.

PMID- 25380642
TI  - Metabolism of reactive oxygen species in cytoplasmic male sterility of rice by
      marking upmost pulvinus interval.
AB  - Reactive oxygen species (ROS) and malondialdehyde (MDA) in plant cell are thought
      to be important inducible factors of cell apoptosis if excessively accumulated in
      cells. To elucidate the metabolic mechanism of MDA production and scavenging in
      the cytoplasmic male-sterile (CMS) rice, CMS line and maintainer were employed
      for studying the relationship at different developmental stages by marking upmost
      pulvinus interval method of experiment. The results showed that the panicles and
      leaves of the CMS line had a noticeable higher MDA content than those of
      maintainer line at all five stages that had been investigated (p < 0.05). MDA
      content in the CMS line in the flag leaves of auricle in the distance 0 mm stage
      (the meiosis stage) was the highest of the five stages. The increase of MDA
      contents in sterile panicles and leaves had inducible effects on the enzymic
      activity of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD).
      However, at the abortion peak stage, MDA was excessively accumulated and
      antioxidant enzymic activity reduced significantly, resulting in the generation
      and scavenging of MDA out of balance.

PMID- 25380643
TI  - Cytotoxicity of zinc oxide nanoparticles on antioxidant enzyme activities and
      mRNA expression in the cocultured C2C12 and 3T3-L1 cells.
AB  - The present study was aimed to investigate the dose-dependent effect of zinc
      oxide (ZnO) nanoparticles on antioxidant enzyme activities and messenger RNA
      (mRNA) expression in the cocultured C2C12 and 3T3-L1 cells. Coculturing
      experiments are 3D and more reliable compared to mono-culture (2D) experiment.
      Even though, there are several studies on ZnO nanoparticle-mediated cytotoxicity,
      but there are no studies on the effect of ZnO nanoparticle on antioxidant enzyme
      activities and mRNA expression in the cocultured C2C12 and 3T3-L1 cells. A
      cytotoxicity assay was carried out to determine the effect of ZnO nanoparticles
      on the C2C12 and 3T3-L1 cell viability. At higher concentration of ZnO
      nanoparticles, C2C12 and 3T3-L1 cells almost die. ZnO nanoparticles increased
      reactive oxygen species (ROS) and lipid peroxidation and reduced glutathione
      (GSH) levels in a dose-dependent manner in the C2C12 and 3T3-L1 cells. In
      addition, ZnO nanoparticles increased antioxidant enzyme activities and their
      mRNA expression in the C2C12 and 3T3-L1 cells. In conclusion, the present study
      showed that ZnO nanoparticles increased oxidative stress, antioxidant enzyme
      activities, and their mRNA expression in the cocultured C2C12 and 3T3-L1 cells. 

PMID- 25380644
TI  - Successful management of a patient with a C3 Glomerulonephritis and crescentic
      pattern: a case report.
AB  - BACKGROUND: Crescentic glomerulonephritis is a rare condition in children and is
      typically associated with renal insufficiency. Dysfunction of the alternative
      complement pathway is an unusual aetiology with an unknown mechanism. CASE
      PRESENTATION: We report a case of a previously healthy 12-year-old Caucasian girl
      who was examined on emergency owing to an asymptomatic gross haematuria. An
      active urinary sediment and nephrotic-range proteinuria were identified, and
      serologic examination showed a decreased serum C3 concentration not associated
      with any immunologic or infectious cause. Oedema, hypertension, and renal
      insufficiency were not observed. A renal biopsy was performed, and crescentic
      glomerulonephritis associated with C3 glomerulonephritis was diagnosed. Prompt
      treatment with intravenous steroids resulted in complete resolution of the gross
      haematuria. Further examination did not detect any underlying acquired cause. A
      combination of oral steroids and cyclophosphamide, followed by mycophenolate
      mofetil, was maintained and resulted in clinical remission during an 8-month
      follow-up. CONCLUSION: The presence of severe injury such as crescentic
      glomerulonephritis secondary to C3 glomerulonephritis is extremely unusual in
      children. This is the first known case of paediatric crescentic
      glomerulonephritis secondary to C3 glomerulonephritis that presented with gross
      haematuria and was treated early and effectively with immunosuppressive therapy
      based on its severe histologic features.

PMID- 25380645
TI  - Interactive impacts of a herbivore and a pathogen on two resistance types of
      Barbarea vulgaris (Brassicaceae).
AB  - It is well known that pathogens and arthropod herbivores attacking the same host
      plant may affect each other. Little is known, however, about their combined
      impact on plant fitness, which may differ from simple additive expectations. In a
      2-year common garden field experiment, we tested whether the pathogen Albugo sp.
      (white blister rust) and the herbivorous flea beetle Phyllotreta nemorum affected
      each other's performance on two resistance types (G-type and P-type) of the
      crucifer Barbarea vulgaris ssp. arcuata, and whether biomass, reproduction and
      survival of the plants were affected by interactive impacts of the antagonists.
      Most of the insect-resistant G-plants were severely affected by white rust, which
      reduced biomass and reproductive potential compared to the controls. However,
      when also exposed to flea beetles, biomass loss was mitigated in G-plants, even
      though apparent disease symptoms were not reduced. Most of the insect-susceptible
      P-plants were resistant to white rust; however, the number of flea beetle mines
      tended to increase in plants also exposed to Albugo, and biomass at the last
      harvest was slightly lower in the combined treatment. Thus, interactive impacts
      of the herbivore and pathogen differed between the two resistance types, with an
      antagonistic combined impact in G-plants, which lasted surprisingly long, and a
      slight synergistic impact in P-plants. 

PMID- 25380646
TI  - Incidence and clinical significance of lesions presenting as a scalp mass in
      adult patients.
AB  - BACKGROUND: Lesions initially presenting as a scalp mass are quite common
      entities with a wide spectrum of causes. They may be directly related to the
      scalp itself or may be secondary stigmata of an underlying process in the skull.
      The rate and clinical significance of the differential diagnosis of these lesions
      are not well studied in the adult population. METHODS: Three hundred sixty
      patients were operated on for scalp masses at our hospital between January 2011
      and February 2014. The patients were defined retrospectively by using the
      hospital coding system for scalp lesions. Among these patients, 15 were excluded
      for being younger than 16 years old. RESULTS: A total of 345 patients, consisting
      of 172 females (49.9 %) and 173 males (50.1 %), were included in the study. The
      mean age at diagnosis was 44.3 (16-89). There were no mortalities during the
      follow-up period (mean 17.99 months). Mean numbers of scalp lesions and surgeries
      were 1.25 and 1.18, respectively. There were 32 distinct histopathological
      diagnoses, the 5 most common being trichilemmal cyst, epidermal cyst, lipoma,
      nevus and sebaceous cyst in order of frequency. The rate of "clinically
      significant" pathologies, meaning malignancies or those needing follow-up, was
      around 7.8 %. The incidence of correct preoperative diagnosis with respect to the
      departments was 13-27 %. CONCLUSIONS: Our series indicated that generally scalp
      masses were underestimated and detailed preoperative diagnostic workup or
      interdisciplinary consultations were not performed regularly. The overall
      incidence of clinically significant lesions warrants a high degree of vigilance
      for accurate diagnosis and management of these lesions, because their etiology
      can be so variable and challenging.

PMID- 25380647
TI  - Effect of saponin on the phytoextraction of Pb, Cd and Zn from soil using Italian
      ryegrass.
AB  - Chemically enhanced phytoextraction has been proposed as an effective approach to
      remove metals from contaminated soil through the Italian ryegrass (Lolium
      multiflorum Lam.). The bioconcentration factor (BCF) and translocation factor
      (TF) are important determinants for phytoextraction of metals. In microcosm
      experiments, effects of saponin on the uptake of Pb, Zn and Cd by Italian
      ryegrass were studied. Results of BCF indicated that Italian ryegrass was the
      most efficient in Zn uptake, followed by Cd and Pb (Zn > Cd > Pb). TF results
      were identical to the BCF results. In addition, the effect of metal stress on
      antioxidative enzyme activity was studied. Results revealed that under the metal
      stress, saponin played an important role in the antioxidative activities of
      Italian ryegrass.

PMID- 25380648
TI  - Impacts of geochemical and environmental factors on seasonal variation of heavy
      metals in a coastal lagoon Yucatan, Mexico.
AB  - This study investigated the influence of geochemical and environmental factors on
      seasonal variation in metals in Yucatan's Chelem lagoon. Anthropogenic activities
      discharge non-treated wastewater directly into it with detrimental environmental
      consequences. Accordingly, this study established the spatial and temporal
      patterns of fine grain sediments and concentrations of heavy metals. Multivariate
      analyses showed fine grain facies deposition, transition sites dominated by fine
      grain transport, and fine grain erosion sites. Spatial and temporal variations of
      heavy metals concentration were significant for Cd, Cu, Cr, and Pb. As, Cd, and
      Sn were as much as 12 times higher than SQuiRTs standards (Buchman 2008). The
      results indicate that aquifer water is bringing metals from relatively far inland
      and releasing them into the lagoon. Thus, it appears that the contamination of
      this lagoon is highly complex and must take into account systemic connections
      with inland anthropogenic activates and pollution, as well as local factors. 

PMID- 25380649
TI  - Screening concentration of E1, E2 and EE2 in sewage effluents and surface waters
      of the "Pampas" region and the "Rio de la Plata" estuary (Argentina).
AB  - Concentrations of estrone (E1), 17beta-estradiol (E2) and 17alpha
      ethinylestradiol (EE2) were investigated for the first time in sewage effluents
      and receiving waters of the "Rio de la Plata" estuary and neighboring areas by
      means of LC-MS/MS. E2 and EE2 were ubiquitous in the evaluated sewage effluent
      samples showing concentrations ranging between 122-631 and 65-187 ng/L,
      respectively. In surface waters, these estrogens were only detected in the
      "Girado" stream (Chascomus) at 369 and 43 ng/L, respectively. No significant
      relationship was found among the size of the served population and the
      concentration of the estrogens in the sewage effluent. The detection of these
      estrogens in receiving waters was dependent on the dilution capacity of the
      system. The studied estrogens were undetectable at the La Plata City water supply
      station. Conversely, concentrations found at the "Girado" stream indicate a
      potential ecotoxicological risk of these estrogens to the local aquatic biota.

PMID- 25380651
TI  - Equilibrium conformational ensemble of the intrinsically disordered peptide n16N:
      linking subdomain structures and function in nacre.
AB  - n16 is a framework protein family associated with biogenic mineral stabilization,
      thought to operate at three key interfaces in nacre: protein/beta-chitin,
      protein/protein, and protein/CaCO3. The N-terminal half of this protein, n16N, is
      known to be active in conferring this mineral stabilization and organization.
      While some details relating to the stabilization and organization of the mineral
      are known, the molecular mechanisms that underpin these processes are not yet
      established. To provide these molecular-scale details, here we explore current
      hypotheses regarding the possible subdomain organization of n16N, as related to
      these three interfaces in nacre, by combining outcomes of Replica Exchange with
      Solute Tempering molecular dynamics simulations with NMR experiments, to
      investigate the conformational ensemble of n16N in solution. We verify that n16N
      lacks a well-defined secondary structure, both with and without the presence of
      Ca(2+) ions, as identified from previous experiments. Our data support the
      presence of three different, functional subdomains within n16N. Our results
      reveal that tyrosine, chiefly located in the center of the peptide, plays a
      multifunctional role in stabilizing conformations of n16N, for intrapeptide and
      possibly interpeptide interactions. Complementary NMR spectroscopy data confirm
      the participation of tyrosine in this stabilization. The C-terminal half of n16N,
      lacking in tyrosine and highly charged, shows substantive conformational
      diversity and is proposed as a likely site for nucleation of calcium carbonate.
      Finally, dominant structures from our predicted conformational ensemble suggest
      the presentation of key residues thought to be critical to the selective binding
      to beta-chitin surfaces.

PMID- 25380652
TI  - Assessing exposures to household air pollution in public health research and
      program evaluation.
AB  - Exposure to smoke from the use of solid fuels and inefficient stoves for cooking
      and heating is responsible for approximately 4 million premature deaths yearly.
      As increasing investments are made to tackle this important public health issue,
      there is a need for identifying and providing guidance on best practices for
      exposure and stove performance monitoring, particularly for public health
      research and evaluation studies. This paper, which builds upon the discussion at
      an expert consultation on exposure assessment convened by the Global Alliance for
      Clean Cookstoves, the Centers for Disease Control and Prevention, and PATH in
      late 2012, aims to provide general guidance on what to monitor, who and where to
      monitor, and how to monitor household air pollution exposures. In addition, we
      summarize information about commercially available monitoring equipment and the
      technical properties of these monitors most important for household air pollution
      exposure assessment. The target audience includes epidemiologists conducting
      health studies and program evaluators aiming to quantify changes in exposures to
      estimate the potential health benefits of cookstoves intervention projects. 

PMID- 25380653
TI  - Organizational readiness for knowledge translation in chronic care: a Delphi
      study.
AB  - BACKGROUND: Health-care organizations need to be ready prior to implement
      evidence-based interventions. In this study, we sought to achieve consensus on a
      framework to assess the readiness of health-care organizations to implement
      evidence-based interventions in the context of chronic care. METHODS: We
      conducted a web-based modified Delphi study between March and May 2013. We
      contacted 76 potentially eligible international experts working in the fields of
      organizational readiness (OR), knowledge translation (KT), and chronic care to
      comment upon the 76 elements resulting from our proposed conceptual map. This
      conceptual map was based on a systematic review of the existing frameworks of
      Organizational Readiness for Change (ORC) in health-care. We developed a
      conceptual map that proposed a set of core concepts and their associated 17
      dimensions and 59 sub-dimensions. Experts rated their agreement concerning the
      applicability and importance of ORC elements on a 5-point Likert scale, where 1
      indicates total disagreement and 5 indicates total agreement. Two rounds were
      needed to get a consensus from the experts. Consensus was a priori defined as
      strong (>=75%) or moderate (60-74%). Simple descriptive statistics was used.
      RESULTS: In total, 14 participants completed the first round and 10 completed the
      two rounds. Panel members reached consensus on the applicability and importance
      of 6 out of 17 dimensions and 28 out of 59 sub-dimensions to assess OR for KT in
      the context of chronic care. A strong level of consensus (>=75%) was attained on
      the Organizational contextual factors, Leadership/participation, Organizational
      support, and Motivation dimensions. The Organizational climate for change and
      Change content dimensions reached a moderate consensus (60-74%). Experts also
      reached consensus on 28 out of 59 sub-dimensions to assess OR for KT. Twenty-one
      sub-dimensions reached a strong consensus (>=75%) and seven a moderate consensus
      (60-74%). CONCLUSION: This study results provided the most important and
      applicable dimensions and sub-dimensions for assessing OR-KT in the context of
      chronic care. They can be used to guide the design of an assessment tool to
      improve knowledge translation in the field of chronic care.

PMID- 25380654
TI  - Lauren classification combined with HER2 status is a better prognostic factor in
      Chinese gastric cancer patients.
AB  - BACKGROUND: Lauren-classification and human epidermal growth factor receptor 2
      (HER2) status are two important pathological features of gastric cancer patients.
      The prognostic value of HER2 in gastric cancer remains controversial. Intestinal
      type gastric cancer has better prognosis and higher HER2 positive proportion.
      What is the interaction between these two factors? We hypothesized that a
      combination of Lauren-classification and human epidermal growth factor receptor 2
      (HER2) status (L-H status) might be more meaningful than either factor alone.
      METHODS: We collected 838 gastric cancer patients at all stages who had received
      treatment in our cancer center. This study was registered in the website of
      ClinicalTrials.Gov, with the number NCT01927146. We divided the patients into six
      groups according to their L-H status: Group A, HER2 negative and intestinal type;
      Group B, HER2 positive and intestinal type; Group C, HER2 negative and diffuse
      type; Group D, HER2 positive and diffuse type; Group E, HER2 negative and mixed
      type; and Group F, HER2 positive and mixed type. RESULTS: Diffuse type and
      intestinal type accounted for 51.0% and 33.9%, respectively. The proportion of
      HER2 positive patients was 11.2%, 25.4%, 2.1% and 10.2% in the whole patient
      group, intestinal, diffuse and mixed type, respectively. Median overall survival
      was 34.0 months, 25.3 months, 27.6 months, 19.2 months, 25.9 months and 26.4
      months in the six groups patients, P = 0.053. There was a significant difference
      in survival among the first four groups (P < 0.001). HER2 was an independent
      prognostic factor in the intestinal type and in stage I + II patients, but not in
      the diffuse type or stage III + IV patients. L-H status was an independent
      prognostic factor in patients at all stages. For the diffuse and intestinal
      types, the multivariate analysis showed that HER2 was not an independent
      prognostic factor, while Lauren classification and L-H status were. Moreover, L-H
      status was a better prognostic factor than the Lauren classification.
      CONCLUSIONS: L-H status is a prognostic factor in diffuse and intestinal type
      patients, but not in the mixed type. Patients with HER2 negative and intestinal
      type had the best survival, while patients with HER2 positive status and diffuse
      type had the worst survival.

PMID- 25380655
TI  - Mapping and manipulating the Mycobacterium  tuberculosis transcriptome using a
      transcription  factor overexpression-derived regulatory network.
AB  - BACKGROUND: Mycobacterium tuberculosis senses and responds to the shifting and
      hostile landscape of the host. To characterize the underlying intertwined gene
      regulatory network governed by approximately 200 transcription factors of M.
      tuberculosis, we have assayed the global transcriptional consequences of
      overexpressing each transcription factor from an inducible promoter. RESULTS: We
      cloned and overexpressed 206 transcription factors in M. tuberculosis to identify
      the regulatory signature of each. We identified 9,335 regulatory consequences of
      overexpressing each of 183 transcription factors, providing evidence of
      regulation for 70% of the M. tuberculosis genome. These transcriptional
      signatures agree well with previously described M. tuberculosis regulons. The
      number of genes differentially regulated by transcription factor overexpression
      varied from hundreds of genes to none, with the majority of expression changes
      repressing basal transcription. Exploring the global transcriptional maps of
      transcription factor overexpressing (TFOE) strains, we predicted and validated
      the phenotype of a regulator that reduces susceptibility to a first line anti
      tubercular drug, isoniazid. We also combined the TFOE data with an existing model
      of M. tuberculosis metabolism to predict the growth rates of individual TFOE
      strains with high fidelity. CONCLUSION: This work has led to a systems-level
      framework describing the transcriptome of a devastating bacterial pathogen,
      characterized the transcriptional influence of nearly all individual
      transcription factors in M. tuberculosis, and demonstrated the utility of this
      resource. These results will stimulate additional systems-level and hypothesis
      driven efforts to understand M. tuberculosis adaptations that promote disease.

PMID- 25380656
TI  - Awareness, use, attitude and perceived need for Complementary and Alternative
      Medicine (CAM) education among undergraduate pharmacy students in Sierra Leone: a
      descriptive cross-sectional survey.
AB  - BACKGROUND: The widespread use of CAM around the world requires health
      professionals including pharmacists to have the required knowledge to better
      advise their patients. This has lead to an increased need for the inclusion of
      CAM instruction into the mainstream undergraduate Pharmacy education. This study
      was designed to describe pharmacy students awareness, use, attitude and perceived
      need for CAM education at COMAHS-USL and at the same time, determine how these
      descriptive outcomes are influenced by the socio-demographic variables considered
      in this study. METHODS: A descriptive cross-sectional survey was conducted among
      undergraduate pharmacy students (n = 90) at the College of Medicine and Allied
      Health Sciences, University of Sierra Leone using a structured questionnaire. Chi
      square, fisher exact test, and general linear model univariate analysis were used
      to compare data between independent cohorts. RESULTS: All 90 (100%) of the
      students were aware and have used (except Ayurveda) at least one of the listed
      CAM modalities. Herbal/Botanical/Supplements followed by Spirituality/Prayer were
      the most commonly known and used CAM modalities. Almost two thirds of students
      considered the CAM modalities they have used to be effective and not harmful.
      Overall, pharmacy students had a positive attitude towards CAM (Mean attitudinal
      score = 34.9 +/- 4. 5 (range 19-43)) with fourth and fifth year students showing
      a significantly less positive attitude as compared to the first, second and third
      year (B = -3.203 p = 0.001, 95% confidence interval -5.093 to -1.314). The media
      [53 (58.9%)] was the most frequent source of information about CAM. Nearly all
      students [89 (98.9%)] agreed that CAM knowledge is important to them as future
      pharmacist and that CAM should be included into the Pharmacy curriculum at COMAHS
      USL [81 (90.0%)]. CONCLUSION: Pharmacy students in Sierra Leone are aware of and
      have used at least one of the CAM modalities and do show a positive attitude
      towards CAM. This was demonstrated by their overwhelming endorsement for CAM
      course to be part of the undergraduate pharmacy training at COMAHS-USL. This
      study among others will inform and guide the development and implementation of
      CAM instruction at COMAHS-USL.

PMID- 25380658
TI  - Medication adherence to oral cancer therapy: The promising role of the
      pharmacist.
AB  - Medication adherence to oral cancer therapy is a critical component to achieving
      optimal patient outcomes. As the US population ages, growing numbers of patients
      will be prescribed oral cancer therapy regimens, highlighting the need for
      innovative and scalable solutions. Clinical pharmacists offer tremendous promise
      to help patients improve their adherence to oral cancer therapy. Moreover,
      addition of oral chemotherapy to Centers for Medicare & Medicaid Services (CMS)
      medication adherence quality measures has the potential to improve care and
      result in better therapeutic outcomes with fewer costs for patients and payers.
      Future research is needed to test the use of pharmacist-managed interventions to
      improve adherence to oral cancer therapy. 

PMID- 25380657
TI  - Toxic effects of levofloxacin on rat annulus fibrosus cells: an in-vitro study.
AB  - BACKGROUND: Fluoroquinolones are in wide clinical use as safe and effective
      antibiotics. Articular cartilage, tendons, and epiphyseal growth plates have been
      recognized as targets of fluoroquinolone-induced connective tissue toxicity.
      However, the effects of fluoroquinolones on annulus fibrosus (AF) cells are still
      unknown. MATERIAL/METHODS: The main objective of this study was to investigate
      the effects of levofloxacin, a typical fluoroquinolone antibiotic drug, on rat AF
      cells in vitro. Rat annulus fibrosus (RAF) cells were treated with levofloxacin
      at different concentrations (0, 10, 20, 30, 40, 60, 80, and 90 MUg/ml) and were
      assessed to determine the possible cytotoxic effects of levofloxacin. Inverted
      phase-contrast microscopy was used to accomplish the morphological observation of
      apoptosis of treated cells. Western blot and real-time quantitative RT-PCR (qPCR)
      was used to explore the expression of active caspase-3 and MMP-3. Flow cytometry
      was used to measure the apoptotic incidences. RESULTS: Our study showed that
      levofloxacin, with concentrations at 30, 60, and 90 MUg/ml, induced dose
      dependent RAF cell apoptosis and higher expression of caspase-3 and MMP-3. More
      apoptotic cells were observed by inverted phase-contrast microscopy. Moreover,
      levofloxacin increased the activity of caspase-3, and it also reduced cell
      viability with different concentrations ranging from 10 to 80 MUg/ml.
      CONCLUSIONS: Our study results suggest that levofloxacin has cytotoxic effects on
      RAF cells, characterized by enhancing apoptosis and reducing cell viability, and
      indicate a potential toxic effect of fluoroquinolones on RAF cells.

PMID- 25380659
TI  - Response to Ebola in the US: misinformation, fear, and new opportunities.

PMID- 25380661
TI  - Central auditory processing and migraine: a controlled study.
AB  - BACKGROUND: This study aimed to verify and compare central auditory processing
      (CAP) performance in migraine with and without aura patients and healthy
      controls. METHODS: Forty-one volunteers of both genders, aged between 18 and 40
      years, diagnosed with migraine with and without aura by the criteria of "The
      International Classification of Headache Disorders" (ICDH-3 beta) and a control
      group of the same age range and with no headache history, were included. Gaps-in
      noise (GIN), Duration Pattern test (DPT) and Dichotic Digits Test (DDT) tests
      were used to assess central auditory processing performance. RESULTS: The
      volunteers were divided into 3 groups: Migraine with aura (11), migraine without
      aura (15), and control group (15), matched by age and schooling. Subjects with
      aura and without aura performed significantly worse in GIN test for right ear (p
      = .006), for left ear (p = .005) and for DPT test (p < .001) when compared with
      controls without headache, however no significant differences were found in the
      DDT test for the right ear (p = .362) and for the left ear (p = .190).
      CONCLUSIONS: Subjects with migraine performed worsened in auditory gap detection,
      in the discrimination of short and long duration. They also presented impairment
      in the physiological mechanism of temporal processing, especially in temporal
      resolution and temporal ordering when compared with controls. Migraine could be
      related to an impaired central auditory processing. CLINICAL TRIAL REGISTRATION:
      Research Ethics Committee (CEP 0480.10) - UNIFESP.

PMID- 25380662
TI  - A systematic review of prevalence and risk factors for elder abuse in Asia.
AB  - The number of older victims of domestic violence is expected to increase
      drastically in Asia as many countries are experiencing rapid population aging. In
      2012, 11% of the population in Asia were aged 60 years and over. This is expected
      to rise to 24% by 2050. This article discusses the unique features of Asian
      cultures that are relevant to the understanding of elder abuse and summarizes the
      existing literature looking at the prevalence and risk factors of such abuse in
      Asian populations. 

PMID- 25380660
TI  - Astrogliosis.
AB  - In addition to their many functions in the healthy central nervous system (CNS),
      astrocytes respond to CNS damage and disease through a process called
      astrogliosis. For many decades, astrogliosis was sparsely studied and enigmatic.
      This article examines recent evidence supporting a definition of astrogliosis as
      a spectrum of heterogeneous potential changes in astrocytes that occur in a
      context-specific manner as determined by diverse signaling events that vary with
      the nature and severity of different CNS insults. Astrogliosis is associated with
      essential beneficial functions, but under specific circumstances can lead to
      harmful effects. Potential dysfunctions of astrocytes and astrogliosis are being
      identified that can contribute to, or be primary causes of, CNS disorders,
      leading to the notion of astrocytopathies. A conceptual framework is presented
      that allows consideration of normally occurring and dysfunctional astrogliosis
      and their different roles in CNS disorders. 

PMID- 25380663
TI  - A low dietary intake of cod protein is sufficient to increase growth, improve
      serum and tissue fatty acid compositions, and lower serum postprandial glucose
      and fasting non-esterified fatty acid concentrations in obese Zucker fa/fa rats.
AB  - PURPOSE: Studies in rats suggest that fish proteins may improve lipid and glucose
      regulation and could thus be a potential tool in the treatment of obesity-related
      comorbidities. To date, all published rat studies on dietary fish protein have
      been designed with 50 or 100% of dietary proteins from fish. As it is not common,
      nor advised, to consume fish as the only protein source in a healthy diet,
      mechanistic studies on the effects of diets with low dose fish proteins are
      needed. Here, we investigate whether a low dose of cod protein would affect
      glucose homeostasis and lipid metabolism in obese Zucker fa/fa rats. METHODS:
      Twelve male obese Zucker fa/fa rats consumed diets where cod proteins accounted
      for 25% of the total protein intake with the remaining 75% from casein (COD) or
      100% of protein as casein (CAS) for 4 weeks. RESULTS: Rats fed COD achieved a
      higher body weight without affecting adiposity and thigh muscle mass after 4
      weeks, but liver weight and hepatic cholesterol level were higher than in CAS-fed
      rats. Fasting serum level of non-esterified fatty acids and 2 h postprandial
      glucose level were lower in COD than in CAS. The fatty acid metabolism was
      beneficially affected by the COD diet, with e.g., higher ratio of n-3/n-6 PUFAs
      in serum, liver and adipose tissue when compared to CAS. CONCLUSIONS: A low
      intake of cod protein (25% of protein intake) was sufficient to beneficially
      affect lipid metabolism and postprandial glucose regulation in obese fa/fa rats.

PMID- 25380664
TI  - Case study: using sequence homology to identify putative phosphorylation sites in
      an evolutionarily distant species (honeybee).
AB  - The majority of scientific resources are devoted to studying a relatively small
      number of model species, meaning that the ability to translate knowledge across
      species is of considerable importance. Obtaining species-specific knowledge
      enables targeted investigations of the biology and pathobiology of a particular
      species, and facilitates comparative analyses. Phosphorylation is the most
      widespread posttranslational modification in eukaryotes, and although many
      phosphorylation sites have been experimentally identified for some species,
      little or no data are available for others. Using the honeybee as a test
      organism, this case study illustrates the process of using protein sequence
      homology to identify putative phosphorylation sites in a species of interest
      using experimentally determined sites from other species. A number of issues
      associated with this process are examined and discussed. Several databases of
      experimentally determined phosphorylation sites exist; however, it can be
      difficult for the nonspecialist to ascertain how their contents compare. Thus,
      this case study assesses the content and comparability of several phosphorylation
      site databases. Additional issues examined include the efficacy of homology-based
      phosphorylation site prediction, the impact of the level of evolutionary
      relatedness between species in making these predictions, the ability to translate
      knowledge of phosphorylation sites across large evolutionary distances and the
      criteria that should be used in selecting probable phosphorylation sites in the
      species of interest. Although focusing on phosphorylation, the issues discussed
      here also apply to the homology-based cross-species prediction of other
      posttranslational modifications, as well as to sequence motifs in general. 

PMID- 25380665
TI  - Glucagon-like peptide-1 (GLP-1) receptor agonist prevents development of
      tolerance to anti-anxiety effect of ethanol and withdrawal-induced anxiety in
      rats.
AB  - Despite major advances in the understanding about ethanol actions, the precise
      underlying neurobiological mechanisms for ethanol dependence remain largely
      elusive. We recently reported that inhibition of dipeptidyl-peptidase IV (DPP
      IV), an enzyme responsible for metabolism of endogenous glucagon-like peptide-1
      (GLP-1), delays tolerance to anti-anxiety effect of ethanol and withdrawal
      induced anxiety in rats. Intrigued with this report, present study examined the
      role of glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide in (1)
      acute anti-anxiety effect of ethanol; (2) tolerance to ethanol's anti-anxiety
      effect and (3) ethanol withdrawal-induced anxiety using elevated plus maze (EPM)
      test in rats. Ethanol (2 g/kg, i.p.; 8 % w/v) and liraglutide (50 MUg/kg, i.p.)
      treatments exhibited anti-anxiety effect in EPM test. Doses of ethanol (1.0 or
      1.5 g/kg, i.p.) that were not effective per se elicited anti-anxiety when
      combined with sub-effective dose of liraglutide (25 MUg/kg, i.p.). Rats consuming
      ethanol-diet (6 % v/v) exhibited tolerance to anti-anxiety effect of ethanol from
      day-7 of ethanol consumption. Peak ethanol withdrawal-induced anxiety was
      observed at 8-10 h upon abstinence from ethanol-diet after 15-days consumption.
      Rats on simultaneous once-daily liraglutide treatment (50 MUg/kg, i.p.) neither
      had any signs of tolerance to anti-anxiety effect of ethanol nor did they exhibit
      withdrawal-induced anxiety. IN CONCLUSION: (1) GLP-1 agonist, liraglutide
      exhibited anti-anxiety effect per se; (2) potentiated anti-anxiety effect of
      ethanol; (3) prevented development tolerance to anti-anxiety effect of ethanol
      and (4) prevented withdrawal-induced anxiety. Further studies examining
      intracellular cascade of events contributing to these effects may help to improve
      understanding about role of GLP-1 receptors in ethanol mediated behaviors.

PMID- 25380666
TI  - The low level laser therapy (LLLT) operating in 660 nm reduce gene expression of
      inflammatory mediators in the experimental model of collagenase-induced rat
      tendinitis.
AB  - Tendinopathy is a common disease with a variety of treatments and therapies.
      Laser therapy appears as an alternative treatment. Here, we investigate the
      effects of laser irradiation in an experimental model of tendinitis induced by
      collagenase injection on rats' Achilles tendon, verifying its action in important
      inflammatory markers. Male Wistar rats were used and divided into five groups:
      control saline (C), non-treated tendinitis (NT) and tendinitis treated with
      sodium diclofenac (D) or laser (1 J) and (3 J). The tendinitis was induced by
      collagenase (100 MUg/tendon) on the Achilles tendon, which was removed for
      further analyses. The gene expression for COX-2; TNF-alpha; IL-6; and IL-10 (RT
      PCR) was measured. The laser irradiation (660 nm, 100 mW, 3 J) used in the
      treatment of the tendinitis induced by collagenase in Achilles tendon in rats was
      effective in the reduction of important pro-inflammatory markers such as IL-6 and
      TNF-alpha, becoming a promising tool for the treatment of tendon diseases. 

PMID- 25380667
TI  - In vitro assessment of effects of hyperglycemia on the optical properties of
      blood during coagulation using optical coherence tomography.
AB  - No published reports have demonstrated the capability of the optical coherence
      tomography technique for quantifying the optical coherence tomography signal
      slope, 1/e light penetration depth, and attenuation coefficient of hyperglycemic
      blood by an in vitro assessment. The purpose of this study was to investigate the
      effects of hyperglycemia on optical properties during in vitro blood coagulation
      by optical coherence tomography. Normal whole blood acted as the control group.
      After 1-h coagulation, the average optical coherence tomography signal slope
      decreased approximately 23.3 and 16.7%, and the 1/e light penetration depths
      increased approximately 21.5 and 19.2% for the control and hyperglycemic groups,
      respectively. It could be seen from the 1/e light penetration depth evolution
      curves that the blood coagulation time was about (425 +/- 19) s for normal whole
      blood and (367 +/- 15) s for the hyperglycemic blood. The coagulation time
      decreased 13.6% for the hyperglycemic blood compared with that for normal whole
      blood. There was statistically significant difference in blood coagulation time
      between the hyperglycemic and normal whole blood (p < 0.05). The results
      suggested that hyperglycemia has a procoagulant effect. Our experiment was the
      first reported study of monitoring hyperglycemic blood coagulation using OCT. We
      conclude that OCT is potential technique to quantify and follow the liquid-gel
      transition of hyperglycemic blood coagulation.

PMID- 25380669
TI  - Am I my brother's keeper? A survey of 10 healthcare professions in the
      Netherlands about experiences with impaired and incompetent colleagues.
AB  - BACKGROUND: Dealing with poor individual performance of healthcare professionals
      is essential in patient safety management. The objective of the current study was
      to explore potential differences regarding experiences with impaired and
      incompetent colleagues between a broad range of healthcare professions. METHODS:
      A survey of 10 legally regulated professions in the Netherlands on knowledge on
      dealing with impaired/incompetent colleagues, experiences with such colleagues,
      action taken upon an impaired and incompetent colleague and reasons for not
      taking action. RESULTS: We approached 4348 professionals, of whom 1238 responded
      (28.5%). One-third of the respondents (31.3%) had an experience with an impaired
      or incompetent colleague in the preceding 12 months, and 84% of these reported
      cases concerned incompetence. Even under the extreme assumption that all non
      respondents had no such experiences, our results indicate that at least 9% of the
      total sample had dealt with an impaired or incompetent colleague in the previous
      12 months. Two-thirds of the professionals (68.6%) who had an experience reported
      having acted upon it. Respondents significantly less often reported to have acted
      (49.6% vs 79.1%, p=0.000) when the colleague was working at a different
      organisation. The primary reason for not taking action was that
      impairment/incompetence could not be proven. CONCLUSIONS: Even using an extreme
      correction for our low response rate, at least 9% of healthcare professionals
      reported dealing with impaired or incompetent colleagues in the past year.
      Creating and clarifying reporting opportunities when confronted with an
      incompetent or impaired colleague should be a priority for professional
      organisations, policymakers and regulatory bodies.

PMID- 25380670
TI  - A first-degree relative with diabetes mellitus is an important risk factor for
      rural Thai villagers to develop type 2 diabetes mellitus.
AB  - The screening of 609 villagers in rural areas of northeastern Thailand resulted
      in the detection of 110 (18.1%) new cases of type 2 diabetes (T2DM). The
      diagnoses were made on the basis of a glycated hemoglobin (HbA1c) value <= 6.5%.
      Among all those screened, 243 (40%) reported having a father or mother with T2DM.
      Among the new cases, 66 (60%) reported a first-degree relative, predominantly
      their mothers, who had the disease. Together with age and the body mass index, a
      mother or father with DM was strong risk factor for the development of T2DM
      (adjusted odds ratio = 2.9, 95% confidence interval = 1.84-4.57) when compared
      with the absence of a first-degree relative with DM. It is concluded that family
      history of a first-degree relative is an important additional information that
      might improve the validity of the screening procedure.

PMID- 25380671
TI  - Idiopathic pericarditis and pericardial effusion in children: contemporary
      epidemiology and management.
AB  - BACKGROUND: Multicenter studies on idiopathic or viral pericarditis and
      pericardial effusion (PPE) have not been reported in children. Colchicine use for
      PPE in adults is supported. We explored epidemiology and management for inpatient
      hospitalizations for PPE in US children and risk factors for readmission. METHODS
      AND RESULTS: We analyzed patients in the Pediatric Health Information System
      database for (1) a code for PPE; (2) absence of codes for underlying systemic
      disease (eg, neoplastic, cardiac, rheumatologic, renal); (3) age >=30 days and
      <21 years; and (4) discharge between January 1, 2007, and December 31, 2012, from
      38 hospitals contributing complete data for each year of the study period. Among
      11 364 hospitalizations with PPE codes during the study period, 543 (4.8%) met
      entry criteria for idiopathic or viral PPE. Significantly more boys were noted,
      especially among adolescents. No temporal trends were noted. Median age was 14.5
      years (interquartile range 7.3 to 16.6 years); 78 patients (14.4%) underwent
      pericardiocentesis, 13 (2.4%) underwent pericardiotomy, and 11 (2.0%) underwent
      pericardiectomy; 157 (28.9%) had an intensive care unit stay, including 2.0% with
      tamponade. Median hospitalization was 3 days (interquartile range 2 to 4 days).
      Medications used at initial admission were nonsteroidal anti-inflammatory drugs
      (71.3%), corticosteroids (22.7%), aspirin (7.0%), and colchicine (3.9%).
      Readmissions within 1 year of initial admission occurred in 46 of 447 patients
      (10.3%), mostly in the first 3 months. No independent predictors of readmission
      were noted, but our statistical power was limited. Practice variation was noted
      in medical management and pericardiocentesis. CONCLUSIONS: Our report provides
      the first large multicenter description of idiopathic or viral PPE in children.
      Idiopathic or viral PPE is most common in male adolescents and is treated
      infrequently with colchicine.

PMID- 25380672
TI  - Glyceria maxima as new test species for the EU risk assessment for herbicides: a
      microcosm study.
AB  - In its recent guidance document on tiered risk assessment for plant protection
      products for aquatic organisms, the European Food Safety Authority (EFSA)
      proposed to use Glyceria maxima as monocotyledonous grass species for the testing
      of special herbicide groups. However, published toxicity data for this species is
      very limited and there is no test guideline for Glyceria sp. For this reason a
      microcosm study was conducted in order to gain experience on the degree of
      sensitivity of G. maxima to the herbicidal substances clodinafop-propargyl (grass
      herbicide) and fluroxypyr (auxin) in comparison to the already established test
      organism water milfoil Myriophyllum spicatum and the duckweed species Landoltia
      punctata. Five concentrations without replicates were tested for each test
      substance using 10 microcosms and three microcosms served as controls. The
      experiment was run for 8 weeks. Morphological endpoints were used to determine
      growth and EC50 values. The results show that M. spicatum was most sensitive to
      fluroxypyr (37 days EC50 for roots: 62 ug/L) and G. maxima most sensitive to
      clodinafop-propargyl (22 days EC50 for total shoot length: 48 ug/L) whereas the
      duckweed species was considerable less sensitive. Hence, G. maxima turns out to
      be a good candidate for testing grass specific herbicides, supporting its
      inclusion as an additional macrophyte test for the risk assessment of herbicides
      as proposed by the EFSA. 

PMID- 25380673
TI  - Malariometric indices from Iganga, Uganda: baseline characterization in
      preparation of GMZ2 vaccine trial.
AB  - BACKGROUND: Malaria still remains the leading cause of childhood morbidity and
      mortality in Uganda. Interventions like malaria vaccines which reduce the malaria
      burden are needed in malaria endemic communities. There is need to establish
      baseline characteristics in vaccine trial study sites. This study determined the
      following baseline malariometric indices: spleen rates, bed net use, malaria
      parasitaemia and malaria episodes in an inception cohort of children aged 12 - 60
      months in Iganga district, Uganda. METHODS: In a longitudinal cohort study, 748
      children were enrolled with 397 in an active follow up arm and 351 in a passive
      arm. The children in the two arms were followed for 6 months to determine the
      incidence of malaria episodes. RESULTS: The overall baseline spleen rate was 8.2%
      (61/748) among the study participants. Of the households surveyed, about 36%
      reported using bed nets and almost 30% of the users had insecticide-treated nets.
      274 (36.6%) of the study participants had a history of fever in the past 24 hrs
      at the time of the baseline survey. All participants had a peripheral blood smear
      for malaria parasites done at enrollment with 76.8% having the asexual form of
      malaria parasites. The malaria episodes per child per year were 1.5 and 0.79 in
      the active and passive follow up arms respectively. CONCLUSIONS: There is a high
      prevalence of malaria asexual parasitaemia in children below five years. The bed
      net usage still remains low among this population. These baseline malariometric
      indices have important implication for malaria control interventions.

PMID- 25380675
TI  - Acute exercise increases resistance to oxidative stress in young but not older
      adults.
AB  - A single bout of acute exercise increases oxidative stress and stimulates a
      transient increase in antioxidant enzymes. We asked whether this response would
      induce protection from a subsequent oxidative challenge, different from that of
      exercise, and whether the effects were affected by aging. We compared young (20
      +/- 1 years, n = 8) and older (58 +/- 6 years, n = 9) healthy men and women.
      Resistance to oxidative stress was measured by the F2-isoprostane response to
      forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R
      trial twice, in random order; once after performing 45 min of cycling on the
      preceding day (IRX) and a control trial without any physical activity (IRC).
      Baseline F2-isoprostane levels were significantly lower at IRX compared to IRC (P
      < 0.05) and not different between groups. F2-isoprostane response to IRX was
      significantly lower compared to IRC in young (P < 0.05) but not different in the
      older group. Superoxide dismutase activity in response to acute exercise was
      significantly higher in young compared to older adults (P < 0.05). These data
      suggest that signal transduction of acute exercise may be impaired with aging.
      Repeated bouts of transient reactive oxygen species production as seen with
      regular exercise may be needed to increase resistance to oxidative stress in
      older individuals. 

PMID- 25380676
TI  - Effect of iron supplementation on the expression of hypoxia-inducible factor and
      antioxidant status in rats exposed to high-altitude hypoxia environment.
AB  - Iron and oxygen are essential substance for cellular activity in body tissues.
      Hypoxia-inducible factors (HIFs) can respond to available oxygen changes in the
      cellular environment and regulate the transcription of a series of target genes.
      The study was conducted to investigate the effects of iron supplementation on the
      expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) and antioxidant
      status in rats exposed to high-altitude hypoxia environment. Forty rats were
      divided into control (CON), hypobaric hypoxia (HH), and hypobaric hypoxia plus
      ferrous sulfate (FeSO4) (9.93 mg/kg body weight (BW)/day) (HFS) and hypobaric
      hypoxia plus iron glycinate chelate (Fe-Gly) (11.76 mg/kg BW/day) (HFG) groups.
      Results showed that Fe-Gly effectively alleviated weight loss and intestinal
      mucosa damage induced by hypobaric hypoxia, whereas FeSO4 aggravated hypobaric
      hypoxia-induced weight loss, liver enlargement, spleen atrophy, and intestinal
      damage. Iron supplementation decreased liver superoxide dismutase (T-SOD) and
      catalase (CAT) activity (P < 0.01) and increased iron concentration in the liver
      compared to HH group (P < 0.001). Moreover, Fe-Gly upregulated liver transferrin
      expression in messenger RNA (mRNA) level (P < 0.05) and downregulated serum
      erythropoietin (EPO) concentration (P < 0.01) and liver HIF-1alpha expression
      level (P < 0.05 in mRNA level; P < 0.001 in protein level) compared to HH group.
      The study indicated that FeSO4 supplementation at high altitudes aggravated the
      oxidative damage of tissues and organs that could be mediated through production
      of malondialdehyde (MDA) and inhibition antioxidant enzyme activities. Fe-Gly can
      protect hypobaric hypoxia-induced tissues injury. Moreover, iron supplementation
      at high altitudes affected HIF-1alpha-mediated regulating expression of targeting
      genes such as EPO and transferrin. The study highlights that iron supplementation
      under hypobaric hypoxia environment has possible limitation, and efficient
      supplementation form and dosage need careful consideration.

PMID- 25380677
TI  - Erratum to: Decreased tongue pressure is associated with sarcopenia and
      sarcopenic dysphagia in the elderly.
AB  - Erratum to: Dysphagia DOI 10.1007/s00455-014-9577-y. In the original publication
      of the article the percentages of sarcopenia in Table 4 were interchanged and
      published incorrectly. The authors apologize for this error and the correct
      version of Table 4 is given below.

PMID- 25380674
TI  - Glycogen synthase kinase-3 as a therapeutic target for cognitive dysfunction in
      neuropsychiatric disorders.
AB  - The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) is involved in a
      broad range of cellular processes including cell proliferation, apoptosis and
      inflammation. It is now also increasingly acknowledged as having a role to play
      in cognitive-related processes such as neurogenesis, synaptic plasticity and
      neural cell survival. Cognitive impairment represents a major debilitating
      feature of many neurodegenerative and psychiatric disorders, including
      Alzheimer's disease, mood disorders, schizophrenia and fragile X syndrome, as
      well as being a result of traumatic brain injury or cranial irradiation.
      Accordingly, GSK-3 has been identified as an important therapeutic target for
      cognitive impairment, and recent preclinical studies have yielded important
      evidence demonstrating that GSK-3 inhibitors may be useful therapeutic
      interventions for restoring cognitive function in some of these brain disorders.
      The current review summarises the role of GSK-3 as a regulator of cognitive
      dependent functions, examines current preclinical and clinical evidence of the
      potential of GSK-3 inhibitors as therapeutic agents for cognitive impairments in
      neuropsychiatric disorders, and offers some insight into the current obstacles
      that are impeding the clinical use of selective GSK-3 inhibitors in the treatment
      of cognitive impairment. 

PMID- 25380678
TI  - Safety and Efficacy of Oral Feeding in Infants with BPD on Nasal CPAP.
AB  - Safety and efficacy of oral feeding was examined in infants with bronchopulmonary
      dysplasia (BPD) on nasal continuous positive airway pressure (NCPAP). We
      hypothesized that repetitive oral feeding enhances aero-digestive outcomes and
      reduces resource utilization. Data from infants with BPD (37-42 weeks post
      menstrual age) that were orally fed while on NCPAP (n = 26) were compared with
      those that were exclusively gavage fed on NCPAP (n = 27). Subject assignment was
      random and physician practice based. Specifically, we compared the differences in
      aero-digestive milestones, resource utilization, and safety metrics. Demographic
      characteristics such as gender distribution, gestational age, and birth weight,
      clinical characteristics such as frequency of intraventricular hemorrhage and
      patent ductus arteriosus needing surgical ligation were similar in both groups (p
      > 0.05). Characteristics of respiratory support and airway milestones were
      similar in both groups (p > 0.05). However, infants in NCPAP-oral fed group had
      earlier acquisition of full oral feeding milestone by 17 days (median) versus
      infants who were not orally fed during NCPAP (p < 0.05). Discharge weights and
      the frequency of gastrostomy tube placement were also similar in both groups (p >
      0.05). There were no tracheostomies in either group. There was no incidence of
      clinically significant aspiration pneumonia in infants during the period of the
      oral feeding while on NCPAP. Controlled introduction of oral feedings in infants
      with BPD during NCPAP is safe and may accelerate the acquisition of oral feeding
      milestones. 

PMID- 25380679
TI  - Effect of phloretin on the binding of 1-anilino-8-naphtalene sulfonate (ANS) to
      1,2-Dimyristoyl-sn-glycero-3-phosphocoline (DMPC) vesicles in the gel and liquid
      crystalline state.
AB  - Phloretin is a known modifier of the internal dipole potential of lipid
      membranes. We studied the interaction of phloretin with model lipid membranes and
      how it influences the membrane dipole organization using ANS as fluorescent
      probe. The fluorescence increase observed when ANS binds to DMPC liposomes in gel
      phase (13  degrees C) was 2.5 times larger in the presence of phloretin. This
      effect was due to an increase in ANS affinity, which can be related to the known
      capability of phloretin in decreasing the dipole potential. Conversely, when the
      experiments were carried out at 33  degrees C (liquid crystalline phase),
      phloretin completely inhibited the increase in ANS fluorescence. In addition,
      phloretin only affected the electrical properties of the membrane in the gel
      phase, whereas it modifies structural ones in the liquid-crystalline state. We
      postulate that phloretin was bound only to the DMPC interface in the gel phase
      decreasing the surface negative charge density without modifying the structural
      properties of the ANS binding sites. In the liquid-crystalline phase instead, it
      increased the accessibility of water to the ANS binding sites decreasing the
      intrinsic affinity and the fluorescence quantum yield of ANS.

PMID- 25380680
TI  - The Ac124 protein is not essential for the propagation of Autographa californica
      multiple nucleopolyhedrovirus, but it is a viral pathogenicity factor.
AB  - orf124 (ac124) of AcMNPV is one of the highly conserved unique genes in group I
      lepidopteran nucleopolyhedroviruses. So far, its function remains unknown. In
      this study, infection with a virus expressing an ac124-gfp fusion showed that
      Ac124 localized to the cytoplasm throughout the infection. In addition, an ac124
      knockout virus was generated to determine the role of ac124 in the baculovirus
      life cycle. Our results showed that an ac124 knockout AcMNPV could produce
      infectious budded viruses (BVs) and occlusion bodies (OBs) like those produced by
      the wild virus and ac124 repair virus. These three viruses had similar growth
      kinetics during the infection phase. There was no significant difference in
      nucleocapsids, occlusion-derived viruses and OBs visualized by electron
      microscopy. The ac124 deletion mutant did not reduce AcMNPV infectivity for S.
      exigua in an LD50 bioassay. However, it took 20 h longer for the ac124 deletion
      mutant to kill S. exigua than wild-type virus in the LT50 bioassay. Altogether,
      these results demonstrate that ac124 is not required for viral replication, but
      it accelerates the killing of infected larvae.

PMID- 25380681
TI  - Aggregates of pseudo-Gaucher cells after treatment of chronic myeloid leukemia in
      blastic phase.

PMID- 25380682
TI  - Contribution of non-infectious transplantation-related complications to the
      outcome of hematopoietic stem cell transplantation in patients with acute myeloid
      leukemia: a single institute analysis.
AB  - Cord blood (CB) is becoming an increasingly attractive alternative stem cell
      source for allogeneic hematopoietic stem cell transplantation (HSCT), but the
      outcomes of CB transplantation (CBT) are inconsistent. In the present study, we
      compared non-infectious transplantation-related complications (NITRCs) post-CBT
      in patients with acute myeloid leukemia (AML) with those following related bone
      marrow and peripheral blood transplantation and unrelated BM transplantation. We
      analyzed 108 patients with AML who received HSCT at the Konan Kosei Hospital
      between 1992 and 2013. After a median follow-up of 74 months, the 3-year overall
      survival (OS) rate was 49.4 % with no differences between graft sources. The
      cumulative incidence of total NITRCs was 36 % at day 100. After adjusted
      analyses, patients with NITRCs showed significantly decreased OS [relative risk
      (RR) 3.51; p < 0.001) and increased non-relapse mortality (NRM) (RR 6.49; p <
      0.001) compared with patients without NITRCs. Although the cumulative NITRC
      incidence did not differ among transplantation groups, NRM in patients with
      NITRCs was significantly lower in CB recipients than in other graft recipients
      (11.2 versus 68.4 %, p = 0.015). These data suggest that NITRCs contribute
      significantly to the outcome of HSCT and that the low virulence of NITRCs favored
      CBT for adult AML.

PMID- 25380684
TI  - Adolescent-parent communication on sexual and reproductive health issues among
      high school students in Dire Dawa, Eastern Ethiopia: a cross sectional study.
AB  - BACKGROUND: Sexual and reproductive health communications are most likely
      promoting healthy sexual development and reduce sexual risks. Communication is
      the principal means for parents to transmit sexual values, beliefs, expectations
      and knowledge to their adolescents. However, there is a paucity of evidence about
      adolescent parent communication in Ethiopia. This study aimed to determine
      adolescent-parent communication on sexual and reproductive health issues and
      associated factors among high school students in Dire Dawa, Eastern Ethiopia.
      METHODS: Institution based cross sectional study was conducted among high school
      students in Dire Dawa administrative council from February to March 2011. Simple
      random sampling technique was used to select 695 students from 9-12 grades.
      Qualitative data were collected through focus group discussion separately for
      female and male parents. Data were entered in Epi info version 3.5.1 and analyzed
      by SPSS version 16.1. Logistic regression with OR and 95% confidence interval was
      used to identify the independent predictors of adolescent parent communication.
      RESULTS: Thirty seven percent of students had ever discussed on at least two
      sexual and reproductive health topics with their parents. Of which, majority of
      student preferred to discuss with their peers than parent. Condom use during
      first intercourse was associated with having communication about sexual and
      reproductive health [AOR=1.9, 95% CI: 1.0, 3.8]. Cultural taboo, shame and lack
      of communication skill were reasons that hinder communication between parent and
      adolescent about sexual matters. CONCLUSION: Communication on sexual and
      reproductive health issue between adolescent and their parent was low. School
      based education is important to improve adolescent parent communication about
      sexual and reproductive health issues.

PMID- 25380683
TI  - [Perioperative pain management: what is evidence based?].
AB  - BACKGROUND: Adequate post-operative acute pain therapy after spinal surgical
      procedures is essential for many patients. However, patients already receiving
      chronic opioid therapy pre-operatively present a special challenge for the
      treating physician during the post-operative period when managing their acute
      pain. The team must consider multiple approaches of acute pain management and it
      is important to proceed according to current evidence-based methods. THERAPY: A
      wide spectrum of options for pain management after spinal surgery is currently
      available. This includes various therapeutic methods as well as regional
      anesthesia. Considering the various options, the method of choice for post
      operative analgesia depends on the expected pain, therapy effectiveness, and the
      applicability with regard to potential side-effects. METHOD: In addition to the
      basic analgesic therapy consisting of opioid and non-opioid drugs, chronic pain
      patients may require co-analgesics or combination analgesics from this class.
      CONCLUSION: Regional anesthesia is currently the predominant method of choice for
      post-operative acute pain management. Neuraxial blockage is especially important
      when considering all spinal procedures.

PMID- 25380686
TI  - Erratum to: Pure Laparoscopic Liver Resection for Large Malignant Tumors: Does
      Size Matter?

PMID- 25380685
TI  - Palliative care training in surgical oncology and hepatobiliary fellowships: a
      national survey of the fellows.
AB  - BACKGROUND: Surgical oncologists (SO) and hepatobiliary (HPB) surgeons frequently
      care for patients with advanced diseases near the end of life, yet little is
      known about their training, comfort, and readiness in the provision of palliative
      care. This study sought to assess the quality, adequacy, and extent of palliative
      care training and the readiness of SO and HPB fellows in delivering palliative
      care. METHODS: A self-administered survey was distributed to all fellows enrolled
      in Society of Surgical Oncology (SSO) and HPB fellowships during the 2013-2014
      academic year. The survey assessed attitudes, training, experience, and readiness
      of fellows in caring for patients at the end of life. Descriptive analysis was
      performed, and Chi square, Student's t test, and the Mann-Whitney U test were
      used to compare mean or median values as appropriate. RESULTS: The response rate
      was 47.2 %, and 50.9 % of the fellows reported exposure to a palliative care
      specialty service during their fellowship. Of the study participants, 75 %
      observed their faculty discussing the side effects of surgery compared with 54 %
      who observed faculty communication with patients regarding end-of-life goals (p <
      0.01). On the other hand, 40 % of the fellows were never observed by faculty
      discussing symptoms management, goals of care, or hospice referral with patients,
      and 56.7 % never received feedback on their palliative skills. CONCLUSION: The
      fellows rated the quality of their palliative care education as poor compared
      with other aspects of their fellowship training, implying the lack and need of
      palliative care teaching. Surgical oncology and HPB fellows and ultimately
      patients may benefit from increased clinical and didactic palliative care
      training.

PMID- 25380687
TI  - Femoroacetabular impingement syndrome--efficacy of surgical treatment with
      regards to age and basic diagnosis.
AB  - PURPOSE: The aim of this study was to assess the outcome of hip preserving
      surgery for femoroacetabular impingement relative to the condition resulting in
      FAI and to the patient's age at the time of the surgery. METHODS: With the
      conditions for exclusion duly met, enrolled in our study were a total of 100 hip
      joints (83 operated on with the aid of SHD, 17 with AMIS). The minimum follow-up
      period was 12 months, and the mean follow-up time was three years four months.
      WOMAC and NAHS questionnaires were used as rating instruments. To analyse the
      significance of the differences relative to the age at the time of surgery and to
      the basic diagnosis leading to FAI and subsequently to surgical operation we used
      non-parametric forms of analysis of variance (Friedman test and Kruskal-Wallis
      test), i.e., comparisons of the patients' pre-operative and postoperative states,
      estimation of the rate of improvement in the postoperative functional skills in
      relation to the age at the time of surgery and/or relative to the basic diagnosis
      necessitating surgical intervention, with respect to statistical significance at
      the level of p < 0.05. RESULTS: As testing of our cohort of patients and results
      analysis showed, the youngest group (<30 years) compared with the rest of the
      cohort shows greater postoperative improvement and consequently also a better
      surgical result. Proof was also obtained that the diagnosis leading to surgery
      for FAI has no effect on the patient's pre- or postoperative state or on the
      degree of improvement. CONCLUSIONS: The results of the study affirm the relevance
      of hip preserving surgery, especially in younger-aged groups.

PMID- 25380688
TI  - Coating with a novel gentamicinpalmitate formulation prevents implant-associated
      osteomyelitis induced by methicillin-susceptible Staphylococcus aureus in a rat
      model.
AB  - PURPOSE: Implant-associated osteomyelitis still represents a demanding challenge
      due to unfavourable biological conditions, bacterial properties and incremental
      resistance to antibiotic treatment. Therefore different bactericide or
      bacteriostatic implant coatings have been developed recently to control local
      intramedullary infections. Controlled local release of gentamicin base from a
      highly lipophilic gentamicin palmitate compound achieves extended intramedullary
      retention times and thus may improve its bactericide effect. METHODS: Forty male
      Sprague-Dawley rats were divided into two groups receiving an intramedullary
      femoral injection of 10(2) colony-forming units (CFU) of a common methicillin
      susceptible Staphylococcus aureus strain (MSSA Rosenbach) and either an uncoated
      femur nail (Group I) or a nail coated with gentamicin palmitate (Group II).
      Animals were observed for 28 and 42 days. Serum haptoglobin and relative weight
      gain were assessed as well as rollover cultures of explanted femur nails and
      histological scores of periprosthetic infection in dissected femurs. RESULTS:
      Implants coated with gentamicin palmitate significantly reduced periprosthetic
      bacterial growth as well as signs of systemic inflammation compared with uncoated
      implants. CONCLUSIONS: Gentamicin palmitate appears to be a viable coating for
      the prevention of implant-associated infections. These findings will have to be
      confirmed in larger animal models as well as in clinical trials.

PMID- 25380689
TI  - IMatter: validation of the NHS Scotland Employee Engagement Index.
AB  - BACKGROUND: Employee engagement is a fundamental component of quality healthcare.
      In order to provide empirical data of engagement in NHS Scotland an Employee
      Engagement Index was co-constructed with staff. 'iMatter' consists of 25 Likert
      questions developed iteratively from the literature and a series of validation
      events with NHS Scotland staff. The aim of this study was to test the face,
      content and construct validity of iMatter. METHODS: Cross sectional survey of NHS
      Scotland staff. In January 2013 iMatter was sent to 2300 staff across all
      disciplines in NHS Scotland. 1280 staff completed it. Demographic data were
      collected. Internal consistency of the scale was calculated. Construct validity
      consisted of concurrent application of factor analysis and Rasch analysis. Face
      and content validity were checked using 3 focus groups. RESULTS: The sample was
      representative of the NHSScotland population. iMatter showed very strong
      reliability (alpha = 0.958). Factor analysis revealed a four-factor structure
      consistent with the following interpretation: CONCLUSIONS: iMatter showed
      evidence of high reliability and validity. It is a popular measure of staff
      engagement in NHS Scotland. Implications for practice focus on the importance of
      coproduction in psychometric development.

PMID- 25380690
TI  - Different protein expression associated with chemotherapy response in
      oropharyngeal cancer according to HPV status.
AB  - BACKGOUND: Oropharyngeal cancer (OPC) associated with human papilloma virus (HPV
      OPC) shows better treatment outcomes than non-HPV OPC. We investigated the
      expression of p53, beta-tubulin, bcl-2 and ERCC 1, which are well-known
      biomarkers to predict the chemotherapy response, according to HPV status in OPC
      patients. METHODS: Patients who treated with at least 2 cycles of induction
      chemotherapy followed by concurrent chemoradiotherapy for locally advanced
      oropharyngeal cancer were reviewed. HPV PCR and immunohistochemical stain was
      done in paraffin embedded tumor tissue and evaluated the relation with the
      chemotherapy response and survival outcomes according to HPV status. RESULTS:
      Seventy-four patients were enrolled for this study and all patients received
      induction chemotherapy with docetaxel, 5-FU and cisplatin. After induction
      chemotherapy, complete response (CR) was shown in 22 patients (30%) and partial
      response (PR) in 46 patients (62%). HPV + was detected in 21 patients (28%),
      while 35 patients (47%) showed p16+ expression by IHC analysis. p16 positive
      patients showed better overall response, PFS and OS than p16 negative patients.
      p53 and class III beta-tubulin expression were significantly higher in HPV- and
      p16- than HPV + and p16+ patients. Conversely, bcl-2 expression was greater in
      HPV + or p16+ than HPV- or p16- patients. ERCC1 expression did not differ
      significantly according to HPV status. In multivariate analyses, early T stage (p
      = 0.036) and good PS (PS 0) (p = 0.029) showed a better 3Y-PFS rate, and low p53
      expression (p = 0.012) and complete response after induction chemotherapy (p =
      0.026) were highly associated with 3Y-OS rate. Low expression of p53 and p16
      positive patients showed significantly prolonged OS than others (p = 0.010).
      CONCLUSION: P53, class III beta-tubulin and bcl-2 were differently expressed in
      OPC according to HPV status and present study suggested the underlying mechanism
      of better response to chemotherapy in case of HPV OPC than non-HPV OPC. Among
      these biomarkers, p53 is the strongest prognostic marker in OPC and p53 in
      addition to p16 support the rationale to study of de-escalation strategy for OPC.

PMID- 25380691
TI  - Application of a high-resolution melting technique for the rapid detection of
      partial replacement of HCV-1b by HCV-1a after PEG-IFNalpha/RBV therapy.
AB  - A modified method which can be used for the rapid screening of mutations in the
      protein kinase R-binding domain (PKR-BD) region and the hypervariable region 1
      (HVR1) of hepatitis C virus (HCV) is described. This method is based on a high
      resolution melting (HRM) technique used for genotyping single nucleotide
      polymorphisms and allows the detection of single nucleotide substitutions in the
      DNA sequence by measuring its Tm. The modified method, in addition to precisely
      measuring the Tm, allows the recording of the melting curve of the investigated
      cDNA fragment, which can provide provisional information about the number of
      different quasi-species present in the sample. The HRM analysis of the amplified
      cDNAs encoding the PKR-BD and HVR1 allowed the detection of partial replacement
      of HCV-1b by HCV-1a subspecies in one of our patients, as well as evaluation of
      the effectiveness of pegylated interferon alpha/ribavirin (PEG-IFNalpha/RBV)
      therapy. The HRM technique has never been used for the rapid screening of
      sequence variations in these regions and may be used for a similar purpose in any
      viral genome. 

PMID- 25380692
TI  - Growth inhibition of Candida species by Wickerhamomyces anomalus mycocin and a
      lactone compound of Aureobasidium pullulans.
AB  - BACKGROUND: The increasing resistance of Candida yeasts towards antifungal
      compounds and the limited choice of therapeutic drugs have spurred great interest
      amongst the scientific community to search for alternative anti-Candida
      compounds. Mycocins and fungal metabolites have been reported to have the
      potential for treatment of fungal infections. In this study, the growth
      inhibition of Candida species by a mycocin produced by Wickerhamomyces anomalus
      and a lactone compound from Aureobasidium pullulans were investigated. METHODS:
      Mycocin was purified from the culture supernatant of an environmental isolate of
      W. anomalus using Sephadex G-75 gel filtration column chromatography. The mycocin
      preparation was subjected to SDS-PAGE analysis followed by MALDI TOF/TOF mass
      spectrometry analysis. The thermal and temperature stability of the mycocin were
      determined. The glucanase activity of the mycocin was investigated by substrate
      staining of the mycocin with 4-methyl-umbelliferyl-beta-D-glucoside (MUG). Gas
      chromatography mass spectrometry (GCMS) analysis was used to identify anti
      Candida metabolite in the culture supernatant of an environmental isolate of
      Aureobasidium pullulans. The inhibitory effects of the anti-Candida compound
      against planktonic and biofilm cultures of various Candida species were
      determined using broth microdilution and biofilm quantitation methods. RESULTS: A
      mycocin active against Candida mesorugosa but not C. albicans, C. parapsilosis
      and C. krusei was isolated from the culture supernatant of W. anomalus in this
      study. The mycocin, identified as exo-beta-1,3 glucanase by MALDI TOF/TOF mass
      spectrometry, was stable at pH 3-6 and temperature ranging from 4-37 degrees C.
      The glucanase activity of the mycocin was confirmed by substrate staining with
      MUG. 5-hydroxy-2-decenoic acid lactone (HDCL) was identified from the culture
      supernatant of A. pullulans. Using a commercial source of HDCL, the planktonic
      and biofilm MICs of HDCL against various Candida species were determined in this
      study. CONCLUSIONS: W. anomalus mycocin demonstrated a narrow spectrum of
      activity targeting only against C. mesorugosa, while HDCL demonstrated a broad
      spectrum of inhibitory action against multiple Candida species. The growth
      inhibition of W. anomalus mycocin and the lactone compound from A. pullulans
      against Candida yeasts should be further explored for therapeutic potentials
      against candidiasis.

PMID- 25380693
TI  - Is mucinous adenocarcinoma of the endometrium a risk factor for lymph node
      involvement? A multicenter case-control study.
AB  - PURPOSE: The purpose of this multicenter case-control study was to compare the
      demographic and clinical characteristics of patients with mucinous adenocarcinoma
      of the endometrium (MAE) and endometrioid endometrial carcinoma (EEC). METHODS: A
      retrospective review of two cancer registry databases in Turkey was conducted to
      identify patients diagnosed with MAE between January 1996 and December 2012. Each
      patient was matched with a control EEC patient by age and tumor grade. Cases and
      controls were compared in terms of known risk factors for lymph node metastasis,
      disease-free survival (DFS), and overall survival (OS). RESULTS: The analysis
      included 112 patients with MAE and 112 with EEC. No significant difference in
      baseline characteristics was evident between the two groups. Lymphovascular space
      invasion, deep myometrial invasion, cervical involvement, and tumor diameter did
      not differ significantly between the mucinous and endometrioid cases.
      Multivariate analysis confirmed that only mucinous histology (OR 2.2, 95 % CI 1.1
      4.5; P = 0.02) was an independent predictor of lymph node involvement. Although
      the median DFS and OS tended to be better in the endometrioid group, the
      differences were not statistically significant. Routine appendectomy was
      performed in 52 (46.2 %) patients with MAE. No mucinous tumor of the appendix was
      identified. CONCLUSION: Routine appendectomy is not necessary when the appendix
      is grossly normal at the time of surgery for MAE. Although the DFS and OS of EEC
      and MAE patients were similar, the risk of nodal metastasis in MAE patients was
      greater than that in ECC patients, and we thus suggest to perform retroperitoneal
      lymphadenectomy (both pelvic and para-aortic) for patients with MAE during the
      initial operation.

PMID- 25380695
TI  - [Hugo von Ziemssen Poster Prize 2014].

PMID- 25380694
TI  - A deep transcriptomic analysis of pod development in the vanilla orchid (Vanilla
      planifolia).
AB  - BACKGROUND: Pods of the vanilla orchid (Vanilla planifolia) accumulate large
      amounts of the flavor compound vanillin (3-methoxy, 4-hydroxy-benzaldehyde) as a
      glucoside during the later stages of their development. At earlier stages, the
      developing seeds within the pod synthesize a novel lignin polymer, catechyl (C)
      lignin, in their coats. Genomic resources for determining the biosynthetic routes
      to these compounds and other flavor components in V. planifolia are currently
      limited. RESULTS: Using next-generation sequencing technologies, we have
      generated very large gene sequence datasets from vanilla pods at different times
      of development, and representing different tissue types, including the seeds,
      hairs, placental and mesocarp tissues. This developmental series was chosen as
      being the most informative for interrogation of pathways of vanillin and C-lignin
      biosynthesis in the pod and seed, respectively. The combined 454/Illumina RNA-seq
      platforms provide both deep sequence coverage and high quality de novo
      transcriptome assembly for this non-model crop species. CONCLUSIONS: The
      annotated sequence data provide a foundation for understanding multiple aspects
      of the biochemistry and development of the vanilla bean, as exemplified by the
      identification of candidate genes involved in lignin biosynthesis. Our
      transcriptome data indicate that C-lignin formation in the seed coat involves
      coordinate expression of monolignol biosynthetic genes with the exception of
      those encoding the caffeoyl coenzyme A 3-O-methyltransferase for conversion of
      caffeoyl to feruloyl moieties. This database provides a general resource for
      further studies on this important flavor species.

PMID- 25380696
TI  - The glutamine-glutamate/GABA cycle: function, regional differences in glutamate
      and GABA production and effects of interference with GABA metabolism.
AB  - The operation of a glutamine-glutamate/GABA cycle in the brain consisting of the
      transfer of glutamine from astrocytes to neurons and neurotransmitter glutamate
      or GABA from neurons to astrocytes is a well-known concept. In neurons, glutamine
      is not only used for energy production and protein synthesis, as in other cells,
      but is also an essential precursor for biosynthesis of amino acid
      neurotransmitters. An excellent tool for the study of glutamine transfer from
      astrocytes to neurons is [(14)C]acetate or [(13)C]acetate and the glial specific
      enzyme inhibitors, i.e. the glutamine synthetase inhibitor methionine sulfoximine
      and the tricarboxylic acid cycle (aconitase) inhibitors fluoro-acetate and 
      citrate. Acetate is metabolized exclusively by glial cells, and [(13)C]acetate is
      thus capable when used in combination with magnetic resonance spectroscopy or
      mass spectrometry, to provide information about glutamine transfer. The present
      review will give information about glutamine trafficking and the tools used to
      map it as exemplified by discussions of published work employing brain cell
      cultures as well as intact animals. It will be documented that considerably more
      glutamine is transferred from astrocytes to glutamatergic than to GABAergic
      neurons. However, glutamine does have an important role in GABAergic neurons
      despite their capability of re-utilizing their neurotransmitter by re-uptake. 

PMID- 25380698
TI  - Validity of a Claims-Based Diagnosis of Obesity Among Medicare Beneficiaries.
AB  - Population-level data on obesity are difficult to obtain. Claims-based data sets
      are useful for studying public health at a population level but lack physical
      measurements. The objective of this study was to determine the validity of a
      claims-based measure of obesity compared to obesity diagnosed with clinical data
      as well as the validity among older adults who suffer from chronic disease. This
      study used data from the National Health and Nutrition Examination Survey 1999
      2004 for adults aged >= 65 successfully linked to 1999-2007 Medicare claims (N =
      3,554). Sensitivity, specificity, positive and negative predictive values, kappa
      statistics as well as logistic regression analyses were computed for the claims
      based diagnosis of obesity versus obesity diagnosed with body mass index. The
      claims-based diagnosis of obesity underestimates the true prevalence in the older
      Medicare population with a low sensitivity (18.4%). However, this method has a
      high specificity (97.3%) and is accurate when it is present. Sensitivity was
      improved when comparing the claim-based diagnosis to Class II obesity (34.2%) and
      when used in combination with chronic conditions such as diabetes, congestive
      heart failure, chronic obstructive pulmonary disease, or depression.
      Understanding the validity of a claims-based obesity diagnosis could aid
      researchers in understanding the feasibility of conducting research on obesity
      using claims data.

PMID- 25380697
TI  - Glial reaction in the spinal cord of the degenerating muscle mouse (Scn8a (dmu)).
AB  - The glial reaction was investigated in the spinal cord of the degenerating muscle
      (dmu) mouse, which harbours a null mutation in the voltage-gated sodium channel
      gene Scn8a and does not produce functional Nav1.6 channel. Glial fibrillary
      acidic protein (GFAP)- and Iba1-immunoreactivity were detected in numerous cells
      throughout the spinal cord of wild type mice. These cells had small cell bodies
      and ramified processes. The dmu mutation increased the number of GFAP
      immunoreactive (-IR) cells and the length of their processes in the ventral horn
      but not in the dorsal horn of the lumbar spinal cord. The number of Iba1-IR cells
      was similar in cervical and lumbar spinal cords of wild type and dmu mice.
      However, Iba1-IR processes and their branches became thinner and showed a fine
      varinose appearance in dmu mice. The length of Iba1-IR processes was
      significantly reduced in dorsal and ventral horns of dmu mice. Double
      immunofluorescence also demonstrated the relationship between glial cells and
      motor neurons containing calcitonin gene-related peptide (CGRP), a marker for
      their degeneration. The dmu mutation caused increase in the length of GFAP-IR
      processes surrounding CGRP-IR motor neurons in the ventral horn. However, the
      thickness and length of Iba1-IR processes around CGRP-IR motor neurons were
      reduced by the mutation. The present study suggests that the dmu mutation causes
      astrocytic activation and microglial inactivation in the spinal cord. These
      changes may be associated with degeneration and activity of motor and sensory
      neuron in dmu mice.

PMID- 25380700
TI  - Ebola is causing moral distress among African healthcare workers.

PMID- 25380699
TI  - Patient Assessment of Chronic Illness Care (PACIC) in Type 2 Diabetes: A
      Longitudinal Study.
AB  - The Patient Assessment of Chronic Illness Care (PACIC) was designed to measure
      care congruent with several elements of the chronic care model (CCM), including
      self-management support and delivery system design. However, support for the a
      priori 5-subscale structure of the PACIC in previous research has been
      conflicting. Thus, we aim to investigate psychometric characteristics of the
      PACIC including the content and stability of its construct over time. A
      population-based prospective cohort study of patients with type 2 diabetes was
      conducted in Queensland, Australia, from 2008 (N = 3,761) to 2010 (N = 3,040).
      Participants completed annually the 20-item PACIC as well as measures of
      providers' adherence to guideline-recommended self-management support activities.
      We used exploratory factor analysis to determine its factor structure and
      examined internal consistency as well as agreement between the PACIC at baseline
      with repeated measurements at follow-up after 1 and 2 years. We also determined a
      criterion-related validity using multinomial logistic regression to explore
      PACIC's association with providers' self-management support. A one-factor
      structure was deemed optimal according to our findings. High internal consistency
      and moderate agreement within the scales over time were observed. Higher PACIC
      scores predicted better providers' self-management support. In conclusion, the
      PACIC is a reliable, valid, and reproducible instrument for assessment of
      diabetes care, and we recommend its promotion and use as a single scale rather
      than subscales as originally proposed.

PMID- 25380701
TI  - The kidney biopsy in lupus nephritis: time to move beyond histology.

PMID- 25380702
TI  - Erratum to: Preoperative Biliary Drainage of Severely Jaundiced Patients
      Increases Morbidity of Pancreaticoduodenectomy: Results of a Case-Control Study.

PMID- 25380703
TI  - A comparison of bleeding complications between warfarin, dabigatran, and
      rivaroxaban in patients undergoing cryoballoon ablation.
AB  - INTRODUCTION: In recent years, several novel anticoagulants have been approved
      for the prevention of thromboembolic strokes as an alternative to warfarin in
      patients with atrial arrhythmias. Studies have evaluated these medications in
      patients undergoing radiofrequency ablation, yet no data exists to evaluate the
      bleeding risk in patients undergoing cryoballoon ablation procedures. METHODS:
      Patients that underwent either cryoballoon ablation alone or with additional
      radiofrequency ablation over the past 3 years were included in the study.
      Patients were stratified into one of three subsets based on type of
      anticoagulation (warfarin, dabigatran, or rivaroxaban). Bleeding complications
      during the first 48 h and first 2 weeks following the ablation were recorded.
      Major complications were defined as hemorrhage requiring blood products or need
      for vascular intervention. Minor complications included prolonged bleeding from
      catheter insertion site, development of ecchymosis, or hematoma formation.
      Intraprocedural activated clotting times (ACT) were assessed and compared.
      RESULTS: A total of 217 patients met inclusion criteria of which 87 (40.1 %)
      patients were on warfarin, 90 (41.5 %) patients on dabigatran, and 40 (18.4 %)
      patients on rivaroxaban. The overall bleeding complication rate was 12.0 %. All
      complications occurred within the first 48 h post-ablation. Nine (10.3 %)
      complications occurred in the warfarin subset, ten (11.1 %) in the rivaroxaban
      subset, and seven (17.5 %) in the dabigatran subset (p = 0.49). The warfarin and
      dabigatran subsets had higher average ACT levels (424.9 versus 406.5) compared to
      the rivaroxaban subset (393.4; p < 0.01). Subanalyses found no difference in
      bleeding complications based on procedure type. CONCLUSION: Bleeding
      complications post-ablation were similar for warfarin, dabigatran, and
      rivaroxaban in patients undergoing cryoballoon ablation. Compared with
      radiofrequency ablation, cryoablation does not place patients at an increased
      bleeding risk.

PMID- 25380704
TI  - Paced QRS axis as a predictor of pacing-induced left ventricular dysfunction.
AB  - PURPOSE: The selection of the optimal right ventricular (RV) pacing site remains
      unclear. We hypothesized that a normal paced QRS axis would provide a
      physiological ventricular activation and lead to a better long-term outcome.
      METHODS: We evaluated 187 patients who underwent a permanent pacemaker
      implantation and were dependent on RV pacing. The pacing sites were classified as
      the apex and non-apex according to the chest radiography. A paced QRS axis was
      defined as that between -30 degrees  and 90 degrees . Preservation of the left
      ventricular (LV) systolic function was defined as that with a <10 % decrease in
      the ejection fraction after the pacemaker implantation. RESULTS: The median
      follow-up period was 5.8 years (interquartile 3.9-9.0). Radiographically, the RV
      leads were located in the apex (n = 148, 79 %) or non-apex (n = 39, 21 %). In the
      electrocardiogram, normal paced and abnormal paced QRS axes were observed in 28
      patients (15 %) and 159 patients (85 %), respectively. The LV ejection fraction
      was decreased in the patients with an abnormal paced QRS axis (-10 +/- 10 %, P <
      0.001), but not in those with a normal axis (0 +/- 6 %, P = 0.80). The
      electrocardiographic determinant differentiated a preserved LV function (95 % vs.
      35 %, log-rank P = 0.04). Among the patients with radiographically non-apical
      pacing, a normal paced QRS axis was an additional meaningful predictor of a
      preserved LV function after the pacemaker implantation (95 % vs. 24 %, log-rank P
      = 0.002). CONCLUSION: Compared with the radiographic method, a normal paced QRS
      axis was associated with a preserved LV function.

PMID- 25380705
TI  - Multiple multisite low-temperature and low-power radiofrequency currents for the
      induction of atrioventricular nodal reentry tachycardia in non-inducible
      patients.
AB  - AIMS: Some patients with documented episodes of paroxysmal supraventricular
      tachycardia (PSVT) do not have inducible tachycardia during the
      electrophysiological study. In this study, we describe how multiple low
      temperature, low-power radiofrequency (RF) currents in the atrioventricular (AV)
      junction region can increase the rate of the induction of atrioventricular nodal
      reentrant tachycardia (AVNRT) in non-inducible cases. METHOD: We enrolled 31
      consecutive patients (mean age = 50.9 +/- 11.9 years; 5 [16.1 %] male) who
      presented with documented clinical PSVT in superficial electrocardiography but
      had non-inducible arrhythmia in the electrophysiology laboratory despite applying
      different stimulation protocols. We delivered low-power (25 W), low-temperature
      (45  degrees C) RF currents into the AV junction region to induce AVNRT. RESULTS:
      Arrhythmia was induced in 20 (64.5 %) patients, and it was non-sustained in 3
      (9.6 %) patients. RF current was delivered into the posterior region near the
      coronary sinus ostium and midseptal region. RF ablation target in inducible
      patients was the non-inducibility of the AVNRT at the end of the procedure, while
      the target in the non-inducible patients was slow pathway ablation with no
      antegrade conduction over the slow pathway. During the follow-up period, none of
      the patients (either with inducible or non-inducible arrhythmia) had recurrence
      of AVNRT. CONCLUSION: Multiple low-power, low-temperature RF current application
      into the AV junction region is a more effective method for the induction of AVNRT
      in comparison with a single current use into the slow pathway.

PMID- 25380706
TI  - Prospective study of acute complication rates and associated risk factors in
      endoscopic therapy for duodenal adenomas.
AB  - BACKGROUND: Endoscopic therapy for duodenal adenomas is becoming increasingly
      important. However, only a few studies have been published on the topic, mainly
      with retrospective data. METHODS: This prospective study was carried out to
      determine complication rates and associated risk factors during and after
      endoscopic therapy for duodenal adenomas. Between May 2011 and October 2012, 50
      patients (with 61 duodenal adenomas) were included. Sixty-one duodenal adenomas
      were resected endoscopically. Complications (e.g., bleeding, pain, fever,
      pancreatitis, and perforation) were recorded. Associations between bleeding and
      other factors--sex, age, anticoagulation, location and size of adenomas,
      etiology, lesion morphology, resection type, and argon plasma coagulation (APC)
      for bleeding prophylaxis--were then investigated. RESULTS: Bleeding was the main
      complication. Major bleeding occurred in four cases (6.5%) and minor bleeding in
      11 (18%). One occult perforation also occurred. There was a statistically
      significant association between bleeding and the size of the adenoma (P = 0.012).
      APC for bleeding prophylaxis showed a promising trend, with an odds ratio of
      0.31, reducing the bleeding risk by two-thirds in this study. However, due to the
      small number of six patients that received bleeding prophylaxis with APC therapy,
      this result was not statistically significant (P = 0.31). CONCLUSIONS: Bleeding
      is the main complication in endoscopic therapy for duodenal adenomas. The
      bleeding risk increases significantly with adenoma size. Prophylactic APC seems
      to reduce the bleeding rate--however, because of the relatively small number of
      patients treated with APC, this partial result was not statistically relevant.
      Due to the relevant rate of complications, endoscopic resection of duodenal
      adenomas is only recommended in an in-patient setting.

PMID- 25380707
TI  - Laparoscopic anti-reflux revision surgery after transoral incisionless
      fundoplication is safe and effective.
AB  - BACKGROUND: Transoral incisionless fundoplication (TIF) treats gastroesophageal
      reflux disease (GERD) by creating a full-thickness esophagogastric plication
      using transmural fasteners. If unsuccessful, revision laparoscopic anti-reflux
      surgery (rLARS) may be performed. This study evaluated operative findings and
      clinical outcomes of rLARS in 28 patients with prior primary TIF. METHODS:
      Intraoperative findings, complications, and symptomatic outcomes with GERD health
      related quality of life (GERD-HRQL) were evaluated prospectively in patients
      having rLARS after TIF. Results are median with interquartile range (IQR).
      RESULTS: Between 03/2009 and 08/2013, 28 patients underwent rLARS at 14 (13-50)
      months post-TIF for recurrent symptoms after initial improvement. Pre-rLARS
      endoscopies found hiatal hernia (9) and wrap disruption (12). All revisions were
      completed laparoscopically in 88 (70-90) min. Eight patients underwent partial
      fundoplication, the rest Nissen. No intraoperative or postoperative complications
      occurred. Operative findings included: No axial hernia in 65%; Dense adhesions in
      14%; Fasteners incorporating the lateral crus in 95%; Traction diverticuli from
      esophagus to crura in 21%. Residual plication was noted anteriorly in 75%,
      posteriorly in 0%. Operative approaches: (1) Areas where the TIF fundoplication
      remained were left intact. This necessitated rolling the fundoplication over the
      fused area to prevent an endoscopic appearance of 'fold'. (2) Fasteners were cut
      and left to migrate into the lumen, rather than being pulled out. (3) In 8
      patients with fusion of the lateral crus to TIF fundoplication and no axial
      hernia, revision fundoplication was performed without mediastinal mobilization
      but with posterior hernia repair. One patient required subsequent surgery for
      small paraesophageal hernia, one for refractory gas-bloat after rLARS. Dysphagia
      in 2 patients resolved with dilation. GERD-HRQL improved from a median of 20 (8
      27) pre-TIF and 10 (1-20) pre-rLARS to 3 (0-4) at 28 months (12-40) post-rLARS (p
      = 0.020 for pre-rLARS to post-rLARS). CONCLUSION: rLARS after TIF can be
      performed safely with excellent clinical outcomes.

PMID- 25380709
TI  - Outcomes of linear-stapled versus hand-sewn gastrojejunal anastomosis in
      laparoscopic Roux en-Y gastric bypass.
AB  - BACKGROUND: In laparoscopic Roux en-Y gastric bypass (LRYGB), the gastrojejunal
      anastomosis (GJA) may be performed using linear-stapled (LS) or completely hand
      sewn (HS) techniques. No published study has compared operative and clinical
      outcomes following LS and HS LRYGB when performed by surgeons beyond the learning
      curve. This study examined outcomes of both techniques performed by two
      'technique-specific' bariatric fellowship-trained surgeons. METHODS: Data on
      consecutive primary LRYGB undertaken in two university hospitals were
      prospectively collected over 28-months and included demographics, co-morbidities,
      postoperative morbidity, mortality, length of stay (LOS), reoperations, and
      excess weight loss (EWL). Data were presented as mean +/- SD. RESULTS: There were
      366 LRYGB studied (LS = 144 and HS = 222 patients) with 96 % 12-month follow-up.
      All procedures were completed laparoscopically with no anastomotic leak or
      mortality. The LS cohort had a lower body mass index (48.3 +/- 5.0 vs 53.8 +/-
      7.1, P < 0.001), greater incidence of diabetes mellitus (P = 0.009) and sleep
      apnea (P = 0.007). The HS cohort had more patients in Obesity Surgery Mortality
      Risk Score classes B and C (P = 0.004 and P = 0.01), and shorter operating time
      (127 +/- 30 vs 172 +/- 30 min, P < 0.001). There were no differences in LOS,
      complications, or reoperations. The HS technique was associated with more GJA
      stenoses requiring endoscopic dilatation (7.7 vs 0 %, P < 0.001). At 12 months,
      EWL (%) was comparable between the two techniques (LS 71.0 +/- 15.5 vs HS 66.5 +/
      13.7, P = 0.09). CONCLUSIONS: When performed by 'technique-specific' surgeons,
      both LS and HS GJA in LRYGB may be performed safely with no significant
      differences in morbidity, reoperations, or EWL.

PMID- 25380710
TI  - Evaluation of pre- and post-operative symptoms in patients submitted to linear
      stapler nodulectomy due to anterior rectal wall endometriosis.
AB  - BACKGROUND: The objective of this study was to evaluate the feasibility and
      safety of a more versatile rectosigmoid nodulectomy technique using a linear
      stapler. METHODS: Case series. SETTING: tertiary care (reference center for
      endometriosis surgery). PATIENTS: Sixty-one consecutive patients who were
      operated on between January 2006 and February 2013. INTERVENTION: anterior rectal
      wall nodulectomy technique using sequential bites of the linear stapler.
      MEASUREMENTS: Perioperative complications were recorded, and a condition-specific
      bowel dysfunction quality of life questionnaire (Rome III--Constipation) was
      applied pre-operatively and post-operatively during the first week of April 2013.
      DESIGN CLASSIFICATION: Canadian Task Force III RESULTS: A total of 61 patients
      were submitted to the intervention. After a mean follow-up period of 1.83 years
      (.25-7.1 +/- 1.97), no post-operative fistula or leakage was observed. In
      addition, no cases of rectal stenosis or bowel obstruction were recorded, and two
      patients were excluded for not answering the post-operative questionnaire.
      According to the Rome III questionnaire, constipation symptoms improved
      significantly in 12 out of 17 questions. No patient reported worsening of
      symptoms in question. CONCLUSIONS: Linear stapler resection is a safe alternative
      to segmentar resection for endometriotic nodules on the anterior rectal wall.

PMID- 25380711
TI  - Heavy metals in the irrigation water, soils and vegetables in the Philippi
      horticultural area in the Western Cape Province of South Africa.
AB  - The aims of this study were to investigate the extent of heavy metal
      contamination in the Philippi horticultural area in the Western Cape Province,
      South Africa. Concentrations of Cd, Cr, Cu, Mn, Ni, Pb and Zn were determined in
      the irrigation water, soils and vegetables in both winter and summer cropping
      seasons with an ICP-AES and tested against certified standards. Differences were
      found in heavy metal concentrations between the winter and summer cropping
      seasons in the irrigation water, soils and vegetables. Certain heavy metals
      exceeded the maximum permissible concentrations in the irrigation water, soils
      and vegetables produced in South Africa. These toxic concentrations were
      predominantly found in the summer cropping season for the soils and in the crops
      produced in winter. It is thus suggested that further studies are carried out in
      the Philippi horticultural area to determine the sources of the heavy metals to
      try and mitigate the inputs thereof and therefore reduce the amount of heavy
      metals entering the human food chain. 

PMID- 25380712
TI  - Mercury contamination in the estuaries and coastal sediments of the Strait of
      Malacca.
AB  - Sediment is a great indicator for assessing coastal mercury contamination. This
      work profiled the magnitude of mercury pollution in the tropical estuaries and
      coastal sediments of the Strait of Malacca. Mercury was extracted through the
      ultrasound-assisted mercury extraction method and analyzed using the flow
      injection mercury system. The mean concentration of mercury in the sediment
      samples was 61.43 +/- 23.25 MUg/kg, ranging from 16.55 +/- 0.61 to 114.02 +/-
      1.54 MUg/kg. Geoaccumulation index revealed that a total of 13% of sampling sites
      were moderately enriched with mercury. The northern part of the Strait of Malacca
      had the highest mean mercury (Hg) concentration (76.36 +/- 27.25 MUg/kg),
      followed by the southern (64.59 +/- 16.09 MUg/kg) and central (39.33 +/- 12.91
      MUg/kg) parts. Sediment mercury concentration in the current study was lower than
      other regions like Japan, China, Indian, east Mediterranean, and Taiwan. When
      compared to the Canadian interim marine and freshwater sediment, China's soil
      interim environmental guidelines, mercury contamination in the Strait of Malacca
      was found to be below these permissible limits. Sediment organic matter content
      was found to have significant correlation with sediment mercury concentration.
      This study could provide the latest benchmark of mercury pollution and prove
      beneficial to future pollution studies in relation to monitoring works in
      tropical estuaries and coastal sediments.

PMID- 25380713
TI  - Field dissipation of trifloxystrobin and its metabolite trifloxystrobin acid in
      soil and apples.
AB  - The dissipation of trifloxystrobin and its metabolite trifloxystrobin acid in
      apples and soil was studied, and the half-life (DT50) was estimated in a field
      study carried out at three different locations for apples and four different
      locations for soil. Trifloxystrobin was sprayed on apples at 127 g a.i./ha for
      the dissipation study. Samples of apple and soil for the dissipation experiment
      were collected at time intervals of 0, 1, 3, 7, 14, 21, 30, and 45 days after
      treatment. The quantification of residues was done by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). The DT50 of trifloxystrobin ranged from 0.54
      to 8.8 and 4.8 to 9.5 days in soil and apples at different latitude sites.
      Photolysis may be the main dissipation pathway for trifloxystrobin, and the
      number of sunshine hours may be the main factor affecting the trifloxystrobin
      dissipation rate in the field. For trifloxystrobin acid residues in soil and
      apples, it first increased and then began decreasing. It was indicated that the
      risk of trifloxystrobin application in shorter sunshine hour area should be
      considered.

PMID- 25380714
TI  - Integration of multi-disciplinary geospatial data for delineating agroecosystem
      uniform management zones.
AB  - Understanding agricultural ecosystems and their complex interactions with the
      environment is important for improving agricultural sustainability and
      environmental protection. Developing the necessary understanding requires
      approaches that integrate multi-source geospatial data and interdisciplinary
      relationships at different spatial scales. In order to identify and delineate
      landscape units representing relatively homogenous biophysical properties and eco
      environmental functions at different spatial scales, a hierarchical system of
      uniform management zones (UMZ) is proposed. The UMZ hierarchy consists of seven
      levels of units at different spatial scales, namely site-specific, field, local,
      regional, country, continent, and globe. Relatively few studies have focused on
      the identification of the two middle levels of units in the hierarchy, namely the
      local UMZ (LUMZ) and the regional UMZ (RUMZ), which prevents true eco
      environmental studies from being carried out across the full range of scales.
      This study presents a methodology to delineate LUMZ and RUMZ spatial units using
      land cover, soil, and remote sensing data. A set of objective criteria were
      defined and applied to evaluate the within-zone homogeneity and between-zone
      separation of the delineated zones. The approach was applied in a farming and
      forestry region in southeastern Ontario, Canada, and the methodology was shown to
      be objective, flexible, and applicable with commonly available spatial data. The
      hierarchical delineation of UMZs can be used as a tool to organize the spatial
      structure of agricultural landscapes, to understand spatial relationships between
      cropping practices and natural resources, and to target areas for application of
      specific environmental process models and place-based policy interventions. 

PMID- 25380715
TI  - Research on phosphorus loads and characteristics of adsorption and release in
      surface sediments of Nanyang Lake and Weishan Lake in China.
AB  - The characteristics of phosphate adsorption and the transformation of phosphorus
      forms in the release process of the sediments in Nanyang Lake and Weishan Lake
      are researched. Distribution of maximal amount of phosphorus adsorbed (Q max) is
      112.76 and 93.91 mg kg(-1), respectively, and the adsorption processes of Nanyang
      Lake and Weishan Lake reach equilibrium after 48 h. Total maximal amount of
      phosphorus adsorbed is the amount of Q max and native adsorbed phosphorus (NAP).
      The m is the sum of the adsorption efficiency of the sediments adsorbing the
      phosphorus coming from external sources and the phosphorus desorbed from the
      sediments. Mutual transformation between phosphorus forms exists in the process
      of phosphorus release. The contents of NH4Cl-P, BD-P, and HCl-P in the sediments
      reduced, and the content of NaOH-P increased in the process. But the amount of
      NaOH-P increased is less than the amount of NH4Cl-P, BD-P, and HCl-P reduced. So
      other forms of phosphorus transformation relations exist. 

PMID- 25380716
TI  - Adjusting the effect of seasonal variability in the bioassessment of streams.
AB  - Bioassessment tools should distinguish between the effects of anthropogenic
      degradation in communities and natural temporal changes. The present study tests
      the influence of natural seasonal variability on macroinvertebrate stream
      communities assessed by a predictive model (PORTRIV) and a multimetric index
      (IPtI) calibrated for spring. The scores of PORTRIV decreased significantly
      between spring and autumn, and between spring and winter (ca. 37 to 53%,
      respectively), while those of IPtI did not change significantly between seasons.
      For non-reference samples, the results of the predictive model also indicate no
      significant differences. A correction factor (CF) was calculated to adjust the
      existing differences in the model assessments between seasons, based on the
      percentage of variation of reference site scores from spring to autumn and
      winter. After the application of the CF to the OE50 scores of spring reference
      samples, the differences were no longer significant. Independent reference
      validation sites confirmed this tendency. This method has the advantage of
      avoiding large efforts required for the construction of databases from other
      seasons and the development of new models to allow the assessment of streams in
      seasons other than spring. Further tests with models developed in regions with
      more marked seasonal changes should be done to confirm its wider applicability.

PMID- 25380717
TI  - Earthworm responses to different reclamation processes in post opencast mining
      lands during succession.
AB  - This study provides earthworm population data obtained from localities with a
      substantial anthropogenic impact spoils. The spoil heaps were reclaimed at the
      end of an opencast brown coal mining period. We studied spoils reclaimed by the
      two most commonly used reclamation processes: forestry and agricultural. The
      results show the significance of the locality age and the utilized reclamation
      process and treatment and their effect on earthworm communities. Our data
      indicate that apart from soil physical and chemical properties, the reclamation
      process itself may also induce viability and distribution of earthworm
      communities. Under standardized soil properties, the changes in earthworm
      populations during the succession were larger within the agricultural reclamation
      process as opposed to the forestry reclamation process for earthworm ecological
      groups and individual species. 

PMID- 25380718
TI  - Exclusive breastfeeding among women taking HAART for PMTCT of HIV-1 in the Kisumu
      Breastfeeding Study.
AB  - BACKGROUND: One of the most effective ways to promote the prevention of mother-to
      child transmission (PMTCT) of HIV-1 in resource-limited settings is to encourage
      HIV-positive mothers to practice exclusive breastfeeding (EBF) for the first 6
      months post-partum while they receive antiretroviral therapy (ARV). Although EBF
      reduces mortality in this context, its practice has been low. We studied the rate
      of adherence to EBF and assessed associated maternal and infant characteristics
      using data from a phase II PMTCT clinical trial conducted in Western Kenya which
      included a counseling intervention to encourage EBF by all participants. METHODS:
      We analyzed data from the Kisumu Breastfeeding Study (KiBS), conducted between
      July 2003 and February 2009. This study enrolled a total of 522 HIV-1 infected
      pregnant women. Data on breastfeeding were available for 480 mother-infant pairs.
      Infant feeding and general nutrition counseling began at 35 weeks gestation and
      continued throughout the 6 month post-partum intervention period, following World
      Health Organization (WHO) infant feeding guidelines. Data on infant feeding were
      collected during routine clinic visits and home visits using food frequency
      questionnaires and dietary recall methods. Participants were instructed to
      exclusively breastfeed until initiation of weaning at 5.5 months post-partum. We
      used Kaplan-Meier methods to estimate the rates of EBF at 5.25 months post
      partum, stratified by maternal and infant characteristics measured at enrollment,
      delivery, and 2 weeks post-partum. RESULTS: The estimated EBF rate at 5.25 months
      post-partum was 80.4%. Only 3% of women introduced other foods (most commonly
      water with or without glucose, cow's milk, formula, and fruit) by 2 months; this
      percentage increased to 5% of women by 4 months. Women who had >=3 previous
      births (p < 0.01) and who were not living with the infant's father (p = 0.04)
      were more likely to exclusively breastfeed. Mixed feeding was more common for
      male infants than for female infants (p = 0.04). CONCLUSION: Exclusive
      breastfeeding was common in this clinical trial, which emphasized EBF as a best
      practice until infants reached 5.5 months of age. Counseling initiated prior to
      delivery and continued during the post-partum period provided a consistent
      message reinforcing the benefits of EBF. The findings from this study suggest
      high adherence to EBF in resource limited settings can be achieved by a
      comprehensive counseling intervention that encourages EBF.

PMID- 25380719
TI  - 454 Pyrosequencing reveals diversity of Bdellovibrio and like organisms in fresh
      and salt water.
AB  - Bdellovibrio-and-like organisms (BALOs) are Gram-negative, predatory bacteria
      that inhabit terrestrial, freshwater and saltwater environments. They have been
      detected primarily by culture-dependent methods which have limitations. In this
      study, diversity and community structure of BALOs in freshwater and saltwater
      samples were characterized by 16S rRNA gene pyrosequencing with specific BALO
      group primers. Novel Bacteriovorax 16S rDNA sequences were found both in
      saltwater enrichment cultures and in situ environmental samples, but no new
      operational taxonomic units were detected in the freshwater samples. The results
      revealed unexpected diversity of BALOs and advance understanding of the
      similarities and differences between Bdellovibrio and Bacteriovorax diversity and
      distribution in the environment. 

PMID- 25380708
TI  - European Association of Endoscopic Surgeons (EAES) consensus statement on the use
      of robotics in general surgery.
AB  - Following an extensive literature search and a consensus conference with subject
      matter experts the following conclusions can be drawn: 1. Robotic surgery is
      still at its infancy, and there is a great potential in sophisticated
      electromechanical systems to perform complex surgical tasks when these systems
      evolve. 2. To date, in the vast majority of clinical settings, there is little or
      no advantage in using robotic systems in general surgery in terms of clinical
      outcome. Dedicated parameters should be addressed, and high quality research
      should focus on quality of care instead of routine parameters, where a clear
      advantage is not to be expected. 3. Preliminary data demonstrates that robotic
      system have a clinical benefit in performing complex procedures in confined
      spaces, especially in those that are located in unfavorable anatomical locations.
      4. There is a severe lack of high quality data on robotic surgery, and there is a
      great need for rigorously controlled, unbiased clinical trials. These trials
      should be urged to address the cost-effectiveness issues as well. 5. Specific
      areas of research should include complex hepatobiliary surgery, surgery for
      gastric and esophageal cancer, revisional surgery in bariatric and upper GI
      surgery, surgery for large adrenal masses, and rectal surgery. All these fields
      show some potential for a true benefit of using current robotic systems. 6.
      Robotic surgery requires a specific set of skills, and needs to be trained using
      a dedicated, structured training program that addresses the specific knowledge,
      safety issues and skills essential to perform this type of surgery safely and
      with good outcomes. It is the responsibility of the corresponding professional
      organizations, not the industry, to define the training and credentialing of
      robotic basic skills and specific procedures. 7. Due to the special economic
      environment in which robotic surgery is currently employed special care should be
      taken in the decision making process when deciding on the purchase, use and
      training of robotic systems in general surgery. 8. Professional organizations in
      the sub-specialties of general surgery should review these statements and issue
      detailed, specialty-specific guidelines on the use of specific robotic surgery
      procedures in addition to outlining the advanced robotic surgery training
      required to safely perform such procedures.

PMID- 25380720
TI  - Nocardiopsis algeriensis sp. nov., an alkalitolerant actinomycete isolated from
      Saharan soil.
AB  - An alkalitolerant actinomycete strain, designated B32(T), was isolated from a
      Saharan soil sample collected from Adrar province (South of Algeria), and then
      investigated using a polyphasic taxonomic approach. The strain was observed to
      produce short chains of spores on the dichotomous branched aerial mycelium and
      formed a fragmented substrate mycelium. The optimum NaCl concentration for growth
      was found to be 0-5 % (w/v) and the optimum growth temperature and pH were found
      to be 25-35  degrees C and 7.0-10.0  degrees C, respectively. The diagnostic
      diamino acid in the cell-wall peptidoglycan was identified as meso-diaminopimelic
      acid. The predominant menaquinones of strain B32(T) were identified as MK-10 (H4)
      and MK-11 (H4). The major fatty acids were found to be iso-C16:0 and anteiso
      C15:0. The diagnostic phospholipids detected were phosphatidylcholine,
      phosphatidylmethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and
      phosphatidylethanolamine. The chemotaxonomic properties of strain B32(T) are
      consistent with those shared by members of the genus Nocardiopsis. 16S rRNA gene
      sequence analysis indicated that strain B32(T) is most closely related to
      Nocardiopsis alba DSM 43377(T) (98.7 %), Nocardiopsis lucentensis DSM 44048(T)
      (98.6 %), Nocardiopsis aegyptia DSM 44442(T) (98.6 %), Nocardiopsis sinuspersici
      HM6(T) (98.6 %) and Nocardiopsis arvandica HM7(T) (98.5 %). However, the DNA-DNA
      relatedness values between strain B32(T) and the closely related type strains
      were 17.9, 14.6, 31.1, 27.1 and 14.1 %, respectively. Based on the combined
      genotypic and phenotypic evidence, it is proposed that strain B32(T) should be
      classified as representative of a novel species, for which the name Nocardiopsis
      algeriensis sp. nov. is proposed. The type strain is B32(T) (=DSM 45462(T) = CECT
      8712(T)).

PMID- 25380721
TI  - Ovary organization and oogenesis in the tardigrade Macrobiotus polonicus Pilato,
      Kaczmarek, Michalczyk & Lisi, 2003 (Eutardigrada, Macrobiotidae): ultrastructural
      and histochemical analysis.
AB  - The female reproductive system, the process of oogenesis, and the morphology of
      the egg capsule of Macrobiotus polonicus were analyzed using transmission and
      scanning electron microscopy and histochemical methods. The female reproductive
      system of Macrobiotus polonicus consists of a single ovary and a single oviduct
      that opens into the cloaca. The seminal receptacle filled with sperm cells is
      present. The ovary is divided into two parts: a germarium that is filled with
      oogonia and a vitellarium that is filled with branched clusters of the germ
      cells. Meroistic oogenesis occurs in the species that was examined. The yolk
      material is synthesized by the oocyte (autosynthesis) and by the trophocytes and
      is transported to the oocyte through cytoplasmic bridges. The process of the
      formation of the egg envelopes starts in the late vitellogenesis. The egg capsule
      is composed of two envelopes-the vitelline envelope and the three-layered
      chorion. The vitelline envelope is of the primary type while the chorion is of a
      secondary type. The surface of the chorion is covered with conical processes that
      terminate with a strongly indented terminal disc.

PMID- 25380722
TI  - Objective measures of the built environment and physical activity in children:
      from walkability to moveability.
AB  - Features of the built environment that may influence physical activity (PA)
      levels are commonly captured using a so-called walkability index. Since such
      indices typically describe opportunities for walking in everyday life of adults,
      they might not be applicable to assess urban opportunities for PA in children.
      Particularly, the spatial availability of recreational facilities may have an
      impact on PA in children and should be additionally considered. We linked
      individual data of 400 2- to 9-year-old children recruited in the European
      IDEFICS study to geographic data of one German study region, based on individual
      network-dependent neighborhoods. Environmental features of the walkability
      concept and the availability of recreational facilities, i.e. playgrounds, green
      spaces, and parks, were measured. Relevant features were combined to a
      moveability index that should capture urban opportunities for PA in children. A
      gamma log-regression model was used to model linear and non-linear effects of
      individual variables on accelerometer-based moderate-to-vigorous physical
      activity (MVPA) stratified by pre-school children (<6 years) and school children
      (>=6 years). Single environmental features and the resulting indices were
      separately included into the model to investigate the effect of each variable on
      MVPA. In school children, commonly used features such as residential density
      [Formula: see text], intersection density [Formula: see text], and public transit
      density [Formula: see text] showed a positive effect on MVPA, while land use mix
      revealed a negative effect on MVPA [Formula: see text]. In particular, playground
      density [Formula: see text] and density of public open spaces, i.e., playgrounds
      and parks combined [Formula: see text], showed positive effects on MVPA. However,
      availability of green spaces showed no effect on MVPA. Different moveability
      indices were constructed based on the walkability index accounting for the
      negative impact of land use mix. Moveability indices showed also strong effects
      on MVPA in school children for both components, expanded by playground density
      [Formula: see text] or by public open space density [Formula: see text], but no
      effects of urban measures and moveability indices were found in pre-school
      children. The final moveability indices capture relevant opportunities for PA in
      school children. Particularly, availability of public open spaces seems to be a
      strong predictor of MVPA. Future studies involving children should consider
      quantitative assessment of public recreational facilities in larger cities or
      urban sprawls in order to investigate the influence of the moveability on
      childhood PA in a broader sample. 

PMID- 25380723
TI  - Immunogenicity of antibody drug conjugates: bioanalytical methods and monitoring
      strategy for a novel therapeutic modality.
AB  - Immunogenicity (the development of an adaptive immune response reactive with a
      therapeutic) is a well-described but unwanted facet of biotherapeutic
      development. There are commonly applied procedures for immunogenicity risk
      assessment, testing strategies, and bioanalysis. With some modifications, these
      can be applied to new biotherapeutic modalities. For novel therapies such as
      antibody-drug conjugates (ADCs), the unique structural components may contribute
      additional complexities to both immunologic responses and bioanalytical methods.
      US product inserts (USPIs) for two commercially available ADCs detail the
      incidence of immunogenicity; however, the body of literature on immunogenicity of
      ADCs is limited. We recently participated in a conference session on this topic
      (Annual meeting of the American Association of Pharmaceutical Scientists, held
      November 2013 in San Antonio, TX, USA. The meeting featured the Symposium:
      Immunogenicity Assessment for Novel Antibody Drug Conjugates, Nonclinical to
      Clinical) which prompted an effort to share our perspectives on how
      immunogenicity risk assessment, testing strategies, and bioanalytical methods can
      be adapted to reflect the complexity of ADC therapeutics.

PMID- 25380724
TI  - Elective orthopedic and cardiopulmonary bypass surgery causes a reduction in
      serum endostatin levels.
AB  - BACKGROUND: Endostatin is an endogenous inhibitor of angiogenesis that inhibits
      neovascularisation. The aim of the study was to evaluate the effect of elective
      surgery on endostatin levels. METHODS: Blood samples were collected prior to
      elective surgery and 4 and 30 days postoperatively in 2 patient groups:
      orthopedic surgery (n =27) and coronary bypass patients (n =21). Serum endostatin
      levels were measured by ELISA. RESULTS: Serum endostatin was significantly
      reduced 30 days after surgery in comparison with presurgical values in both the
      orthopedic (P =0.03) and cardiopulmonary surgery (P =0.04) group. CONCLUSION:
      Serum endostatin is reduced 30 days after surgery. This reduction would favor
      angiogenesis and wound-healing.

PMID- 25380725
TI  - Erratum to: Clinically assessed consequences of workplace physical violence.

PMID- 25380726
TI  - Psychological approach of occupational health service to sick leave due to mental
      problems: a systematic review and meta-analysis.
AB  - PURPOSE: The effects of interventions by occupational health services on sick
      leave prompted by psychiatric disorders were examined with respect to
      intervention method and the number of sick leave days. METHODS: The intervention
      methods used by occupational health services were systematically reviewed by
      searching three databases and manual searching. A meta-analysis of the number of
      sick leave days comparing the intervention group [intervention + care as usual
      (CAU)] and control group (CAU alone) was performed. In addition, subanalyses were
      conducted for the duration until sick-listed workers' return to work after sick
      leave (Subgroup 1) and the number of non-sick-listed workers' total sick leave
      days (Subgroup 2). RESULTS: Ten studies were extracted and integrated, and the
      subjects were subsequently sorted into the intervention group (n = 434, 322, and
      756 in subgroup 1, subgroup 2, and total, respectively) and control group (n =
      413, 385, and 798 in subgroup 1, subgroup 2, and total, respectively). All
      studies employed an intervention method of problem-solving treatment or cognitive
      behavioral therapy (CBT). There were no significant differences between the
      intervention and control groups in subgroup 1 or 2. However, the combined
      intervention group had significantly fewer total sick leave days than the
      combined control group (mean difference -6.64 days, 95% CI -12.68 to -0.59, I(2)
      = 0%). CONCLUSIONS: The combined study of sick-listed and non-sick-listed workers
      indicates occupational health services implement problem-solving treatment or CBT
      interventions, which can shorten total sick leave duration.

PMID- 25380727
TI  - Implementation of collaborative governance in cross-sector innovation and
      education networks: evidence from the National Health Service in England.
AB  - BACKGROUND: Increasingly, health policy-makers and managers all over the world
      look for alternative forms of organisation and governance in order to add more
      value and quality to their health systems. In recent years, the central
      government in England mandated several cross-sector health initiatives based on
      collaborative governance arrangements. However, there is little empirical
      evidence that examines local implementation responses to such centrally-mandated
      collaborations. METHODS: Data from the national study of Health Innovation and
      Education Clusters (HIECs) are used to provide comprehensive empirical evidence
      about the implementation of collaborative governance arrangements in cross-sector
      health networks in England. The study employed a mixed-methods approach,
      integrating both quantitative and qualitative data from a national survey of the
      entire population of HIEC directors (N = 17; response rate = 100%), a group
      discussion with 7 HIEC directors, and 15 in-depth interviews with HIEC directors
      and chairs. RESULTS: The study provides a description and analysis of local
      implementation responses to the central government mandate to establish HIECs.
      The latter represent cross-sector health networks characterised by a vague
      mandate with the provision of a small amount of new resources. Our findings
      indicate that in the case of HIECs such a mandate resulted in the creation of
      rather fluid and informal partnerships, which over the period of three years made
      partial-to-full progress on governance activities and, in most cases, did not
      become self-sustaining without government funding. CONCLUSION: This study has
      produced valuable insights into the implementation responses in HIECs and
      possibly other cross-sector collaborations characterised by a vague mandate with
      the provision of a small amount of new resources. There is little evidence that
      local dominant coalitions appropriated the central HIEC mandate to their own
      ends. On the other hand, there is evidence of interpretation and implementation
      of the central mandate by HIEC leaders to serve their local needs. These findings
      augur well for Academic Health Science Networks, which pick up the mantle of
      large-scale, cross-sector collaborations for health and innovation. This study
      also highlights that a supportive policy environment and sufficient time would be
      crucial to the successful implementation of new cross-sector health
      collaborations.

PMID- 25380728
TI  - 5-hydroxymethylcytosine is not present in appreciable quantities in Arabidopsis
      DNA.
AB  - 5-Hydroxymethylcytosine (5-hmC) is an intermediate in active demethylation in
      metazoans, as well as a potentially stable epigenetic mark. Previous reports
      investigating 5-hydroxymethylcytosine in plants have reached conflicting
      conclusions. We systematically investigated whether 5-hmC is present in plant DNA
      using a range of methods. Using the model organism Arabidopsis thaliana, in
      addition to other plant species, we assayed the amount or distribution of 5
      hydroxymethylcytosine by thin-layer chromatography, immunoprecipitation-chip,
      ELISA, enzymatic radiolabeling, and mass spectrometry. The failure to observe 5
      hydroxymethylcytosine by thin-layer chromatography established an upper bound for
      the possible fraction of the nucleotide in plant DNA. Antibody-based methods
      suggested that there were low levels of 5-hmC in plant DNA, but these experiments
      were potentially confounded by cross-reactivity with the abundant base 5
      methylcytosine. Enzymatic radiolabeling and mass spectrometry, the most sensitive
      methods for detection that we used, failed to detect 5-hydroxymethylcytosine in
      A. thaliana genomic DNA isolated from a number of different tissue types and
      genetic backgrounds. Taken together, our results led us to conclude that 5-hmC is
      not present in biologically relevant quantities within plant genomic DNA. 

PMID- 25380729
TI  - Relationships of RNA polymerase II genetic interactors to transcription start
      site usage defects and growth in Saccharomyces cerevisiae.
AB  - Transcription initiation by RNA Polymerase II (Pol II) is an essential step in
      gene expression and regulation in all organisms. Initiation requires a great
      number of factors, and defects in this process can be apparent in the form of
      altered transcription start site (TSS) selection in Saccharomyces cerevisiae
      (Baker's yeast). It has been shown previously that TSS selection in S. cerevisiae
      is altered in Pol II catalytic mutants defective in a conserved active site
      feature known as the trigger loop. Pol II trigger loop mutants show growth
      phenotypes in vivo that correlate with biochemical defects in vitro and exhibit
      wide-ranging genetic interactions. We assessed how Pol II mutant growth
      phenotypes and TSS selection in vivo are modified by Pol II genetic interactors
      to estimate the relationship between altered TSS selection in vivo and organismal
      fitness of Pol II mutants. We examined whether the magnitude of TSS selection
      defects could be correlated with Pol II mutant-transcription factor double mutant
      phenotypes. We observed broad genetic interactions among Pol II trigger loop
      mutants and General Transcription Factor (GTF) alleles, with reduced-activity Pol
      II mutants especially sensitive to defects in TFIIB. However, Pol II mutant
      growth defects could be uncoupled from TSS selection defects in some Pol II
      allele-GTF allele double mutants, whereas a number of other Pol II genetic
      interactors did not influence ADH1 start site selection alone or in combination
      with Pol II mutants. Initiation defects are likely only partially responsible for
      Pol II allele growth phenotypes, with some Pol II genetic interactors able to
      exacerbate Pol II mutant growth defects while leaving initiation at a model TSS
      selection promoter unaffected. 

PMID- 25380731
TI  - Primary leiomyosarcoma of the anterior mediastinum.

PMID- 25380730
TI  - How big is your Y? A genome sequence-based estimate of the size of the male
      specific region in Megaselia scalaris.
AB  - The scuttle fly, Megaselia scalaris, is often cited as a model in which to study
      early sex chromosome evolution because of its homomorphic sex chromosomes, low
      but measurable molecular differentiation between sex chromosomes, and occasional
      transposition of the male-determining element to different chromosomes in
      laboratory cultures. Counterintuitively, natural isolates consistently show sex
      linkage to the second chromosome. Frequent natural transposition of the male
      determining element should lead to the loss of male specificity of any
      nontransposed material on the previous sex-linked chromosome pair. Using next
      generation sequencing data from a newly obtained natural isolate of M. scalaris,
      we show that even highly conservative estimates for the size of the male-specific
      genome are likely too large to be contained within a transposable element. This
      result strongly suggests that transposition of the male-determining region either
      is extremely rare or has not persisted recently in natural populations, allowing
      for differentiation of the sex chromosomes of this species. 

PMID- 25380733
TI  - Biomarkers of exposure among U.S. cigar smokers: an analysis of 1999-2012
      National Health and Nutrition Examination Survey (NHANES) data.
AB  - BACKGROUND: Cigar consumption is increasing in the United States, but little
      information is available about exposure to toxic constituents from cigar smoking.
      METHODS: We conducted a cross-sectional analysis of biomarkers of tobacco
      exposure among 25,522 participants from the National Health and Nutrition
      Examination Survey (NHANES, 1999-2012). The biomarkers analyzed were serum
      cotinine, urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), blood
      lead, blood cadmium, and urinary arsenic. We calculated geometric mean
      concentrations for each biomarker by tobacco use category and geometric mean
      ratios controlling for demographic factors. RESULTS: Cigar smokers had higher
      cotinine, NNAL, and lead concentrations than nontobacco users. The geometric mean
      concentration [95% confidence interval (CI)] of cotinine for primary cigar
      smokers (i.e., current cigar/never cigarette smokers) was 6.2 (4.2-9.2) ng/mL
      versus 0.045 (0.043-0.048) ng/mL for nontobacco users, and the NNAL concentration
      was 19.1 (10.6-34.3) pg/mg creatinine for primary cigar smokers versus 1.01 (0.95
      1.07) pg/mg creatinine for nontobacco users. Secondary cigar smokers (i.e.,
      current cigar/former cigarette smokers) and dual cigar/cigarette smokers had
      higher cadmium concentrations than nontobacco users. Cigar smoking was associated
      with significantly higher concentrations of cotinine, NNAL, cadmium, and lead,
      after adjusting for demographic factors. Secondary cigar smokers had
      significantly higher cotinine and NNAL concentrations than primary cigar smokers.
      The NNAL concentrations in daily cigar smokers were comparable with those in
      daily cigarette smokers. CONCLUSIONS: Cigar smokers have higher concentrations of
      several toxic and carcinogenic substances than nontobacco users. IMPACT: Our
      results are consistent with epidemiologic evidence demonstrating cigar smoking as
      a cause of disease and premature death.

PMID- 25380732
TI  - The effectiveness of melatonin for promoting healthy sleep: a rapid evidence
      assessment of the literature.
AB  - A systematic review was conducted using Samueli Institute's Rapid Evidence
      Assessment of the Literature (REAL) process to determine the evidence base for
      melatonin as an agent to optimize sleep or improve sleep quality, and generalize
      the results to a military, civilian, or other healthy, active, adult population.
      Multiple databases were searched yielding 35 randomized controlled trials (RCTs)
      meeting the review's inclusion criteria, which were assessed for methodological
      quality as well as for melatonin effectiveness. The majority of included studies
      were high quality (83.0%). Overall, according to Grading Recommendations,
      Assessment Development and Evaluation (GRADE) methodology, weak recommendations
      were made for preventing phase shifts from jet lag, for improving insomnia in
      both healthy volunteers and individuals with a history of insomnia, and for
      initiating sleep and/or improving sleep efficacy. Based on the literature to
      date, no recommendations for use in shift workers or to improve hormonal phase
      shift changes in healthy people can be made at this time. Larger and longer
      duration RCTs utilizing well characterized products are needed to warrant
      melatonin recommendations in young, healthy adults.

PMID- 25380734
TI  - Change in population prevalences of human papillomavirus after initiation of
      vaccination: the high-throughput HPV monitoring study.
AB  - BACKGROUND: Organized human papillomavirus (HPV) vaccination was introduced in
      Sweden in 2012. On-demand vaccination was in effect from 2006 to 2011. We
      followed the HPV prevalences in Southern Sweden from 2008 to 2013. METHODS:
      Consecutive, anonymized samples from the Chlamydia trachomatis screening were
      analyzed for HPV DNA for two low-risk types and 14 high-risk types using PCR with
      genotyping using mass spectrometry. We analyzed 44,146 samples in 2008, 5,224 in
      2012, and 5,815 in 2013. RESULTS: Registry-determined HPV vaccination coverages
      of the population in Southern Sweden increased mainly among 13- to 22-year-old
      women. Most analyzed samples contained genital swabs from women and the HPV6
      prevalence in these samples decreased from 7.0% in 2008 to 4.2% in 2013 [-40.0%;
      P < 0.0005 (chi(2) test)]. HPV16 decreased from 14.9% to 8.7% (-41.6%; P <
      0.0005) and HPV18 decreased from 7.9% to 4.3% (-45.6%; P < 0.0005) among 13- to
      22-year-old women. There were only small changes in vaccination coverage among 23
      to 40-year-old women. In this age group, HPV18 decreased marginally (-19.6%; P =
      0.04) and there were no significant changes for HPV6 or HPV16. Two nonvaccine HPV
      types (HPV52 and HPV56) were increased among 13- to 22-year-old women, both in
      2012 and 2013. CONCLUSIONS: A major reduction of HPV6, 16, and 18 prevalences is
      seen in the age groups with a concomitant increase in HPV vaccination coverage.
      The minor changes seen for nonvaccine types will require further investigation.
      IMPACT: Monitoring of type-specific HPV prevalences may detect early effects of
      HPV vaccination.

PMID- 25380736
TI  - "Alone in Eden: care aides' perceptions of consistent assignments" by Elizabeth
      Anderson and Jude Spiers.

PMID- 25380735
TI  - Changing inequalities in cervical cancer: modeling the impact of vaccine uptake,
      vaccine herd effects, and cervical cancer screening in the post-vaccination era.
AB  - BACKGROUND: Inequalities in cervical cancer may be increased following mass
      vaccination against the human papillomavirus (HPV) if girls with low vaccine
      uptake also have low future participation in cervical cancer screening. We
      evaluated how vaccine uptake distribution affects inequalities in squamous cell
      carcinoma (SCC) incidence between groups with different screening participation.
      METHODS: We used an individual-based transmission dynamic model of HPV infection
      and disease (HPV-ADVISE). Females were stratified by routine screening frequency.
      We modeled the impact of vaccination on SCC incidence rate differences (absolute
      inequality) and incidence rate ratios (relative inequality) between women who
      have routine screening intervals of <5 years (frequently screened), >=5 years
      (underscreened), and who are never screened. We compared simulations with uniform
      vaccine uptake with scenarios with unequal vaccine uptake, in which never and
      underscreened women have lower vaccine uptake than frequently screened women.
      RESULTS: Absolute SCC inequalities between groups with different screening rates
      were predicted to decrease after vaccination, even when women with the lowest
      screening participation had the lowest vaccine uptake. Herd effects helped reduce
      absolute inequalities when vaccine uptake was unequal. Conversely, relative SCC
      inequalities remained unchanged or increased after vaccination. Results were
      robust to different overall vaccination coverages and sexual mixing scenarios.
      CONCLUSION: Though mass HPV vaccination is predicted to substantially decrease
      SCC incidence rates, never screened women will still have the highest disease
      burden after vaccination. IMPACT: To reduce both absolute and relative SCC
      inequalities, public health initiatives will need to address inequalities in both
      vaccine uptake and in cervical cancer screening participation.

PMID- 25380737
TI  - Paying the price for open access.

PMID- 25380738
TI  - Calcifying vascular smooth muscle cells and osteoblasts: independent cell types
      exhibiting extracellular matrix and biomineralization-related mimicries.
AB  - BACKGROUND: Ectopic vascular calcifications represent a major clinical problem
      associated with cardiovascular disease and mortality. However, the mechanisms
      underlying pathological vascular calcifications are largely unknown hampering the
      development of therapies to tackle this life threatening medical condition.
      RESULTS: In order to gain insight into the genes and mechanisms driving this
      pathological calcification process we analyzed the transcriptional profile of
      calcifying vascular smooth muscle cells (C-VSMCs). These profiles were compared
      to differentiating osteoblasts, cells that constitute their physiological
      calcification counterparts in the body. Overall the transcriptional program of C
      VSMC and osteoblasts did not overlap. Several genes, some of them relevant for
      bone formation, were distinctly modulated by C-VSMCs which did not necessarily
      lose their smooth muscle cell markers while calcifying. Bioinformatics gene
      clustering and correlation analysis disclosed limited bone-related mechanisms
      being shared by two cell types. Extracellular matrix (ECM) and biomineralization
      genes represented common denominators between pathological vascular and
      physiological bone calcifications. These genes constitute the strongest link
      between these cells and represent potential drivers for their shared end-point
      phenotype. CONCLUSIONS: The analyses support the hypothesis that VSMC trans
      differentiate into C-VSMCs keeping their own identity while using mechanisms that
      osteoblasts use to mineralize. The data provide novel insights into groups of
      genes and biological processes shared in MSC and VSMC osteogenic differentiation.
      The distinct gene regulation between C-VSMC and osteoblasts might hold clues to
      find cell-specific pathway modulations, opening the possibility to tackle
      undesired vascular calcifications without disturbing physiologic bone formation
      and vice versa.

PMID- 25380739
TI  - Results of sacral nerve neuromodulation for double incontinence in adults.
AB  - Faecal incontinence and urinary incontinence are common and often associated.
      Sacral neurostimulation is a validated technique for treating each of these two
      types of incontinence, taken separately. The purpose of this study was to review
      the literature on the results of this treatment for double incontinence. A
      literature search was conducted using MEDLINE, PubMed, EMBASE and the Cochrane
      Library using the keywords "faecal incontinence", "anal incontinence", "urinary
      incontinence", "urgency", "urinary disorder", "neurostimulation", "sacral nerve
      stimulation" and "electric nerve stimulation". We limited the search to English
      language articles on faecal and urinary incontinence in adults published from
      1995 to the present. We identified six articles, comprising 113 patients who were
      followed for 3-62 months. Improved faecal incontinence was observed in 44-100 %
      of cases, while improved urinary incontinence was observed in 20-100 % of cases.
      Patient satisfaction with the correction of double incontinence, both anal and
      urinary, was highly variable, ranging from 20 to 100 %. As anal incontinence and
      urinary incontinence are often associated and are sometimes responsive to sacral
      neuromodulation, it seems attractive to provide such treatment for double
      incontinence, to improve both digestive and urinary symptoms.

PMID- 25380740
TI  - One-third of patients fail to return to work 1 year after surgery for colorectal
      cancer.
AB  - BACKGROUND: Achieving full recovery after colorectal cancer surgery means a
      return to normal physical and psychological health and to a normal social life.
      Recovery data focusses on time to discharge rather than longer term functionality
      including return to work (RTW). We aim to assess return to normal holistic
      function at 1 year after colorectal cancer surgery. METHOD: Questionnaires were
      created and dispatched to 204 patients who had undergone surgery with curative
      intent for colorectal cancer, in 2011-2012, in a single teaching hospital.
      RESULTS: Response rate was 75 % (153/204), 82 % (129/157) for open surgery (OS)
      and 51 % (24/47) for laparoscopic surgery (LS). Median age was 68 (48-91) years
      for OS and 65 (36-84) for LS. Eighty-four per cent of patients felt 'ready' and
      95 % had adequate pain control upon discharge (no difference between groups). LS
      reported earlier 'return to full fitness' (1-3 months) than OS (>6 months; Mann
      Whitney U, p < 0.05). Recovery from LS was 'better than expected' compared to OS
      'worse than expected' (Mann-Whitney U test, p < 0.05). Forty-nine patients were
      employed preoperatively and 61 % (n = 30) returned to work. RTW was more frequent
      after LS (Chi-square test, p < 0.05). Length of time to RTW was significantly
      less after LS [44 (6-84) days] than OS [71 (14-252) days] (t test, p < 0.05).
      Levels of self-employment were equal between groups. CONCLUSIONS: One-third of
      patients failed to RTW at 1 year post-surgery. Patients having LS returned to
      full fitness faster, felt recovery was shorter and returned to work earlier than
      OS. We must invest more in managing expectations and provide better post
      discharge support to improve RTW.

PMID- 25380741
TI  - Transanal total mesorectal excision: a systematic review of the experimental and
      clinical evidence.
AB  - Achieving a clear distal or circumferential resection margins with laparoscopic
      total mesorectal excision (TME) may be laborious, especially in obese males and
      when operating on advanced distal rectal tumors with a poor response to
      neoadjuvant treatment. Transanal (TaTME) is a new natural orifice translumenal
      endoscopic surgery modality in which the rectum is mobilized transanally using
      endoscopic techniques with or without laparoscopic assistance. We conducted a
      comprehensive systematic review of publications on this new technique in PubMed
      and Embase databases from January, 2008, to July, 2014. Experimental and clinical
      studies written in English were included. Experimental research with TaTME was
      done on pigs with and without survival models and on human cadavers. In these
      studies, laparoscopic or transgastric assistance was frequently used resulting in
      an easier upper rectal dissection and in a longer rectal specimen. To date, 150
      patients in 16 clinical studies have undergone TaTME. In all but 15 cases,
      transabdominal assistance was used. A rigid transanal endoscopic
      operations/transanal endoscopic microsurgery (TEO/TEM) platform was used in 37
      patients. Rectal adenocarcinoma was the indication in all except for nine cases
      of benign diseases. Operative times ranged from 90 to 460 min. TME quality was
      deemed intact, satisfactory, or complete. Involvement in circumferential
      resection margins was detected in 16 (11.8 %) patients. The mean lymph node
      harvest was equal or greater than 12 in all studies. Regarding morbidity,
      pneumoretroperitoneum, damage to the urethra, and air embolism were reported
      intraoperatively. Mean hospital stay varied from 4 to 14 days. Postoperative
      complications occurred in 34 (22.7 %) patients. TaTME with TEM is feasible in
      selected cases. Oncologic safety parameters seem to be adequate although the
      evidence relies on small retrospective series conducted by highly trained
      surgeons. Further studies are expected.

PMID- 25380742
TI  - Extended lateral pelvic sidewall excision (ELSiE): an approach to optimize
      complete resection rates in locally advanced or recurrent anorectal cancer
      involving the pelvic sidewall.
AB  - BACKGROUND: Complete pathological resection of locally advanced or recurrent
      rectal and anal cancer is regarded as one of the most important determinants of
      oncological outcome. Disease in the lateral pelvic sidewall has been considered a
      contraindication for pelvic exenteration surgery owing to the significant
      likelihood of incomplete resection. METHODS: We describe a novel technique
      (ELSiE) to resect disease involving the lateral pelvic sidewall. Patient
      demographics, post-operative histology, length of hospital stay and complications
      were collected from prospectively maintained electronic patient database.
      RESULTS: During 2011-2013, six patients underwent pelvic exenteration surgery
      with the ELSiE approach. All patients had R0 resection. Three patients required
      sciatic nerve excision. Four patients developed post-operative complications
      although no major complications occurred. CONCLUSIONS: Patients with locally
      advanced and recurrent cancer involving the lateral pelvic sidewall may be
      rendered suitable for potentially curative radical resection with a modification
      in the approach to the lateral pelvic sidewall. Our pilot series seems to
      indicate that our novel technique (ELSiE) is feasible, safe and yields high rates
      of complete pathological resection.

PMID- 25380743
TI  - A randomized pilot study on single-port versus conventional laparoscopic rectal
      surgery: effects on postoperative pain and the stress response to surgery.
AB  - BACKGROUND: Potential benefits of single-port laparoscopic surgery may include
      improved cosmetic results, less postoperative pain, surgical trauma and faster
      recovery. Results of randomized prospective studies with a focus on single-port
      rectal surgery have not yet been presented. The aim of the present study was to
      compare single-port and conventional laparoscopic surgery for rectal cancer in
      terms of short-term outcomes including postoperative pain and trauma-induced
      changes in certain bioactive substances. METHODS: Patients with non-metastasized
      rectal cancer were prospectively randomized to single-port (n = 20) or
      conventional laparoscopic rectal surgery (n = 20). Postoperative pain was
      assessed at rest, at coughing and during mobilization, with a numeric pain
      ranking score and was recorded at 6 h after the operation and subsequently every
      morning daily for 4 days. Levels of C-reactive protein (CRP), interleukin-6 (IL
      6) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were determined. Blood
      samples were collected preoperatively (baseline), and 6, 24, 48, 72 and 96 h
      after skin incision. RESULTS: Pain scores were significantly reduced in the
      single-port group on postoperative days 2, 3 and 4 during coughing and
      mobilization. In addition, the patients in the single-port group suffered
      significantly less pain at rest at 6 h after surgery and on postoperative days 1,
      3 and 4. The levels of the three markers increased significantly after surgery.
      The increase was similar between groups for plasma IL-6 and TIMP-1 at all time
      points, while the CRP levels were significantly lower in the single-port group at
      6 (p < 0.001) and 24 h (p < 0.05) after skin incision. Abdominal incisions
      lengths were significantly shorter in the single-port group (p = 0.001). There
      was no significant difference between groups in operating time and blood loss,
      morbidity or mortality rate. The short-term oncological outcome in the two groups
      was similar. CONCLUSIONS: Single-port rectal surgery may reduce postoperative
      pain. Although CRP levels were lower at some time points, results of the present
      randomized, pilot study suggest that the trauma-induced inflammatory response of
      single-port operations may be similar to the trauma-induced inflammatory response
      of conventional laparoscopic surgery.

PMID- 25380744
TI  - Malignant melanoma metastasis to the colon: a curable lesion.

PMID- 25380746
TI  - New insights in the biology of ABC transporters ABCC2 and ABCC3: impact on drug
      disposition.
AB  - INTRODUCTION: For the elimination of environmental chemicals and metabolic waste
      products, the body is equipped with a range of broad specificity transporters
      that are present in excretory organs as well as in several epithelial blood
      tissue barriers. AREAS COVERED: ABCC2 and ABCC3 (also known as MRP2 and MRP3)
      mediate the transport of various conjugated organic anions, including many drugs,
      toxicants and endogenous compounds. This review focuses on the physiology of
      these transporters, their roles in drug disposition and how they affect drug
      sensitivity and toxicity. It also examines how ABCC2 and ABCC3 are coordinately
      regulated at the transcriptional level by members of the nuclear receptor (NR)
      family of ligand-modulated transcription factors and how this can be
      therapeutically exploited. EXPERT OPINION: Mutations in both ABCC2 and ABCC3 have
      been associated with changes in drug disposition, sensitivity and toxicity. A
      defect in ABCC2 is associated with Dubin-Johnson syndrome, a recessively
      inherited disorder characterized by conjugated hyperbilirubinemia.
      Pharmacological manipulation of the activity of these transporters can
      potentially improve the pharmacokinetics and thus therapeutic activity of
      substrate drugs but also affect the physiological function of these transporters
      and consequently ameliorate associated disease states.

PMID- 25380747
TI  - UK built Ebola treatment centre opens in Sierra Leone.

PMID- 25380745
TI  - Antioxidants inhibit the inflammatory and apoptotic processes in an intermittent
      hypoxia model of sleep apnea.
AB  - BACKGROUND: Sleep apnea causes intermittent hypoxia (IH). We aimed to investigate
      the proteins related to oxidative stress, inflammation and apoptosis in liver
      tissue subjected to IH as a simulation of sleep apnea in conjunction with the
      administration of either melatonin (MEL, 200 MUL/kg) or N-acetylcysteine (NAC, 10
      mg/kg). METHODS: Seventy-two adult male Balb-C mice were divided: simulation of
      IH (SIH), SIH + MEL, SIH + NAC, IH, IH + MEL and IH + NAC. The animals were
      subjected to simulations of sleep apnea for 8 h a day for 35 days. The data were
      analyzed with ANOVA and Tukey tests with the significance set at p < 0.05.
      RESULTS: In IH, there was a significant increase in oxidative stress and
      expression of HIF-1a. In addition, we observed increase in the activation levels
      of NF-kB. This increase may be responsible for the increased expression of TNF
      alpha and iNOS as well as the significant increase of VEGF signaling and
      expression of caspase-3 and caspase-6, which suggests an increase in apoptosis.
      In the groups treated with antioxidants, the analysis showed that the enzyme
      activity and protein levels were similar to those of the non-simulated group.
      CONCLUSIONS: Thus, we show that IH causes liver inflammation and apoptosis, which
      may be protected with either MEL or NAC.

PMID- 25380748
TI  - Success rates with nicotine personal vaporizers: a prospective 6-month pilot
      study of smokers not intending to quit.
AB  - BACKGROUND: Electronic cigarettes (e-Cigs) are an attractive long-term
      alternative nicotine source to conventional cigarettes. Although they may assist
      smokers to remain abstinent during their quit attempt, studies using first
      generation e-Cigs report low success rates. Second generation devices (personal
      vaporisers - PVs) may result in much higher quit rates, but their efficacy and
      safety in smoking cessation and/or reduction in clinical trials is unreported.
      METHOD: We conducted a prospective proof-of-concept study monitoring
      modifications in smoking behaviour of 50 smokers (unwilling to quit) switched
      onto PVs. Participants attended five study visits: baseline, week-4, week-8, week
      12 and week-24. Number of cigarettes/day (cigs/day) and exhaled carbon monoxide
      (eCO) levels were noted at each visit. Smoking reduction/abstinence rates,
      product usage, adverse events and subjective opinions of these products were also
      reviewed. RESULTS: Sustained 50% and 80% reduction in cigs/day at week-24 was
      reported in 15/50 (30%) and 7/50 (14%) participants with a reduction from
      25cigs/day to 6cigs/day (p < 0.001) and 3cigs/day (p < 0.001), respectively.
      Smoking abstinence (self-reported abstinence from cigarette smoking verified by
      an eCO <=10 ppm) at week-24 was observed in 18/50 (36%) participants, with 15/18
      (83.3%) still using their PVs at the end of the study. Combined 50% reduction and
      smoking abstinence was shown in 33/50 (66%) participants. Throat/mouth irritation
      (35.6%), dry throat/mouth (28.9%), headache (26.7%) and dry cough (22.2%) were
      frequently reported early in the study, but waned substantially by week-24.
      Participants' perception and acceptance of the products was very good.
      CONCLUSION: The use of second generation PVs substantially decreased cigarette
      consumption without causing significant adverse effects in smokers not intending
      to quit. TRIAL REGISTRATION: (ClinicalTrials.gov Identifier: NCT02124200).

PMID- 25380749
TI  - Aberrant expression of osteopontin and E-cadherin indicates radiation resistance
      and poor prognosis for patients with cervical carcinoma.
AB  - Radiotherapy is the first-line treatment for all stages of cervical cancer,
      whether it is used for radical or palliative therapy. However, radioresistance of
      cervical cancer remains a major therapeutic problem. Consequently, we explored if
      E-cadherin (a marker of epithelial-mesenchymal transition) and osteopontin could
      predict radioresistance in patients with locally advanced cervical squamous cell
      carcinoma (LACSCC). Patients were retrospectively reviewed and 111 patients
      divided into two groups (radiation-resistant and radiation-sensitive groups)
      according to progression-free survival (PFS). In pretreated paraffin-embedded
      tissues, we evaluated E-cadherin and osteopontin expression using
      immunohistochemical staining. The percentage of patients with high osteopontin
      but low E-cadherin expression in the radiation-resistant group was significantly
      higher than those in the radiation-sensitive group (p<0.001). These patients also
      had a lower 5-year PFS rate (p<0.001). Our research suggests that high
      osteopontin but low E-cadherin expression can be considered as a negative,
      independent prognostic factor in patients with LACSCC ([Hazard ratios (95% CI)
      6.766 (2.940, 15.572)], p<0.001).

PMID- 25380750
TI  - Understanding the roles of FAK in cancer: inhibitors, genetic models, and new
      insights.
AB  - Focal adhesion kinase (FAK) is a protein tyrosine kinase that regulates cellular
      adhesion, motility, proliferation and survival in various types of cells.
      Interestingly, FAK is activated and/or overexpressed in advanced cancers, and
      promotes cancer progression and metastasis. For this reason, FAK became a
      potential therapeutic target in cancer, and small molecule FAK inhibitors have
      been developed and are being tested in clinical phase trials. These inhibitors
      have demonstrated to be effective by inducing tumor cell apoptosis in addition to
      reducing metastasis and angiogenesis. Furthermore, several genetic FAK mouse
      models have made advancements in understanding the specific role of FAK both in
      tumors and in the tumor environment. In this review, we discuss FAK inhibitors as
      well as genetic mouse models to provide mechanistic insights into FAK signaling
      and its potential in cancer therapy.

PMID- 25380751
TI  - The Hsp90 cochaperones Cpr6, Cpr7, and Cns1 interact with the intact ribosome.
AB  - The abundant molecular chaperone Hsp90 is essential for the folding and
      stabilization of hundreds of distinct client proteins. Hsp90 is assisted by
      multiple cochaperones that modulate Hsp90's ATPase activity and/or promote client
      interaction, but the in vivo functions of many of these cochaperones are largely
      unknown. We found that Cpr6, Cpr7, and Cns1 interact with the intact ribosome and
      that Saccharomyces cerevisiae lacking CPR7 or containing mutations in CNS1
      exhibited sensitivity to the translation inhibitor hygromycin. Cpr6 contains a
      peptidyl-prolyl isomerase (PPIase) domain and a tetratricopeptide repeat (TPR)
      domain flanked by charged regions. Truncation or alteration of basic residues
      near the carboxy terminus of Cpr6 disrupted ribosome interaction. Cns1 contains
      an amino-terminal TPR domain and a poorly characterized carboxy-terminal domain.
      The isolated carboxy-terminal domain was able to interact with the ribosome.
      Although loss of CPR6 does not cause noticeable growth defects, overexpression of
      CPR6 results in enhanced growth defects in cells expressing the temperature
      sensitive cns1-G90D mutation (the G-to-D change at position 90 encoded by cns1).
      Cpr6 mutants that exhibit reduced ribosome interaction failed to cause growth
      defects, indicating that ribosome interaction is required for in vivo functions
      of Cpr6. Together, these results represent a novel link between the Hsp90
      molecular-chaperone machine and protein synthesis. 

PMID- 25380752
TI  - The Dictyostelium discoideum GPHR ortholog is an endoplasmic reticulum and Golgi
      protein with roles during development.
AB  - Dictyostelium discoideum GPHR (Golgi pH regulator)/Gpr89 is a developmentally
      regulated transmembrane protein present on the endoplasmic reticulum (ER) and the
      Golgi apparatus. Transcript levels are low during growth and vary during
      development, reaching high levels during the aggregation and late developmental
      stages. The Arabidopsis ortholog was described as a G protein-coupled receptor
      (GPCR) for abscisic acid present at the plasma membrane, whereas the mammalian
      ortholog is a Golgi apparatus-associated anion channel functioning as a Golgi
      apparatus pH regulator. To probe its role in D. discoideum, we generated a strain
      lacking GPHR. The mutant had different growth characteristics than the AX2 parent
      strain, exhibited changes during late development, and formed abnormally shaped
      small slugs and fruiting bodies. An analysis of development-specific markers
      revealed that their expression was disturbed. The distributions of the
      endoplasmic reticulum and the Golgi apparatus were unaltered at the
      immunofluorescence level. Likewise, their functions did not appear to be
      impaired, since membrane proteins were properly processed and glycosylated. Also,
      changes in the external pH were sensed by the ER, as indicated by a pH-sensitive
      ER probe, as in the wild type. 

PMID- 25380754
TI  - Evidence for a regulatory role of diatom silicon transporters in cellular silicon
      responses.
AB  - The utilization of silicon by diatoms has both global and small-scale
      implications, from oceanic primary productivity to nanotechnological applications
      of their silica cell walls. The sensing and transport of silicic acid are key
      aspects of understanding diatom silicon utilization. At low silicic acid
      concentrations (<30 MUM), transport mainly occurs through silicic acid transport
      proteins (SITs), and at higher concentrations it occurs through diffusion.
      Previous analyses of the SITs were done either in heterologous systems or without
      a distinction between individual SITs. In the present study, we examined
      individual SITs in Thalassiosira pseudonana in terms of transcript and protein
      abundance in response to different silicic acid regimes and examined knockdown
      lines to evaluate the role of the SITs in transport, silica incorporation, and
      lipid accumulation resulting from silicon starvation. SIT1 and SIT2 were
      localized in the plasma membrane, and protein levels were generally inversely
      correlated with cellular silicon needs, with a distinct response being found when
      the two SITs were compared. We developed highly effective approaches for RNA
      interference and antisense knockdowns, the first such approaches developed for a
      centric diatom. SIT knockdown differentially affected the uptake of silicon and
      the incorporation of silicic acid and resulted in the induction of lipid
      accumulation under silicon starvation conditions far earlier than in the wild
      type cells, suggesting that the cells were artificially sensing silicon
      limitation. The data suggest that the transport role of the SITs is relatively
      minor under conditions with sufficient silicic acid. Their primary role is to
      sense silicic acid levels to evaluate whether the cell can proceed with its cell
      wall formation and division processes. 

PMID- 25380753
TI  - Targeting Toxoplasma tubules: tubulin, microtubules, and associated proteins in a
      human pathogen.
AB  - Toxoplasma gondii is an obligate intracellular parasite that causes serious
      opportunistic infections, birth defects, and blindness in humans. Microtubules
      are critically important components of diverse structures that are used
      throughout the Toxoplasma life cycle. As in other eukaryotes, spindle
      microtubules are required for chromosome segregation during replication.
      Additionally, a set of membrane-associated microtubules is essential for the
      elongated shape of invasive "zoites," and motility follows a spiral trajectory
      that reflects the path of these microtubules. Toxoplasma zoites also construct an
      intricate, tubulin-based apical structure, termed the conoid, which is important
      for host cell invasion and associates with proteins typically found in the
      flagellar apparatus. Last, microgametes specifically construct a microtubule
      containing flagellar axoneme in order to fertilize macrogametes, permitting
      genetic recombination. The specialized roles of these microtubule populations are
      mediated by distinct sets of associated proteins. This review summarizes our
      current understanding of the role of tubulin, microtubule populations, and
      associated proteins in Toxoplasma; these components are used for both novel and
      broadly conserved processes that are essential for parasite survival. 

PMID- 25380755
TI  - Both the charged linker region and ATPase domain of Hsp90 are essential for Rad51
      dependent DNA repair.
AB  - The inhibition of Hsp90 in cancerous cells has been correlated with the reduction
      in double-strand break (DSB repair) activity. However, the precise effect of
      Hsp90 on the DSB repair pathway in normal cells has remained enigmatic. Our
      results show that the Hsp82 chaperone, the ortholog of mammalian Hsp90, is
      indispensable for homologous-recombination (HR)-mediated DNA repair in the
      budding yeast Saccharomyces cerevisiae. A considerable reduction in cell
      viability is observed in an Hsp82-inactivated mutant upon methyl methanesulfonate
      (MMS) treatment as well as upon UV treatment. The loss of Hsp82 function results
      in a dramatic decrease in gene-targeting efficiency and a marked decrease in the
      endogenous levels of the key recombination proteins Rad51 and Rad52 without any
      notable change in the levels of RAD51 or RAD52 transcripts. Our results establish
      Rad51 as a client of Hsp82, since they interact physically in vivo, and also show
      that when Hsp82 is inhibited by 17-AAG, Rad51 undergoes proteasomal degradation.
      By analyzing a number of point mutants with mutations in different domains of
      Hsp82, we observe a strong association between the sensitivity of an ATPase
      mutant of Hsp82 to DNA damage and the decreases in the amounts of Rad51 and Rad52
      proteins. The most significant observations include the dramatic abrogation of HR
      activity and the marked decrease in Rad51 focus formation in the charged linker
      deletion mutant of Hsp82 upon MMS treatment. The charged linker region of Hsp82
      is evolutionarily conserved in all eukaryotes, but until now, no biological
      significance has been assigned to it. Our findings elucidate the importance of
      this region in DNA repair for the first time. 

PMID- 25380756
TI  - Measuring symptomatic relief in men with lower urinary tract symptoms.

PMID- 25380758
TI  - Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal
      obstruction in a general adolescent population.
AB  - BACKGROUND: Exercise-induced respiratory symptoms are common among adolescents.
      Exercise is a known stimulus for transient narrowing of the airways, such as
      exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal
      obstruction (EILO). Our aim was to investigate the prevalence of EIB and EILO in
      a general population of adolescents. METHODS: In this cross-sectional study, a
      questionnaire on exercise-induced dyspnoea was sent to all adolescents born in
      1997 and 1998 in Uppsala, Sweden (n=3838). A random subsample of 146 adolescents
      (99 with self-reported exercise-induced dyspnoea and 47 without this condition)
      underwent standardised treadmill exercise tests for EIB and EILO. The exercise
      test for EIB was performed while breathing dry air; a positive test was defined
      as a decrease of >=10% in FEV1 from baseline. EILO was investigated using
      continuous laryngoscopy during exercise. RESULTS: The estimated prevalence of EIB
      and EILO in the total population was 19.2% and 5.7%, respectively. No gender
      differences were found. In adolescents with exercise-induced dyspnoea, 39.8% had
      EIB, 6% had EILO and 4.8% had both conditions. In this group, significantly more
      boys than girls had neither EIB nor EILO (64.7% vs 38.8%; p=0.026). There were no
      significant differences in body mass index, lung function, diagnosed asthma or
      medication between the participants with exercise-induced dyspnoea who had or did
      not have a positive EIB or EILO test result. CONCLUSIONS: Both EIB and EILO are
      common causes of exercise-induced dyspnoea in adolescents. EILO is equally common
      among girls and boys and can coexist with EIB.

PMID- 25380757
TI  - PART and SNAP.

PMID- 25380759
TI  - A national survey of occupational radiation exposure among diagnostic radiologic
      technologists in South Korea.
AB  - The objective of this study was to investigate representative occupational
      characteristics and radiation exposure for South Korean radiologic technologists.
      The authors conducted a national survey by stratified sampling of South Korean
      administrative districts and types of medical facilities. A total of 585
      technologists were surveyed, and survey data were linked with dosimetry data from
      the National Dose Registry. A total of 73 % of radiologic technologists sampled
      were male, 62 % were younger than age 40 and 86.5 % began employment after 1990.
      The most frequent practices among radiologic technologists were diagnostic
      routine X-ray followed by computed tomography (CT) and portable X-ray. Male
      workers were more frequently involved in CT, portable X-ray and interventional
      radiology whereas female workers carried out most mammography procedures. The
      average annual effective dose was 2.3 mSv for male and 1.3 mSv for female
      workers. The dose was significantly higher for workers in the provinces and those
      who had recently started work.

PMID- 25380760
TI  - Radiation protection culture: a global challenge.
AB  - The central motto 'Radiation Protection Culture-A Global Challenge' of the fourth
      European IRPA Congress is discussed on the basis of the IRPA Guiding Principles
      Establishing a Radiation Protection Culture and the contributions presented in
      the plenary sessions of the conference. 

PMID- 25380761
TI  - Creating a culture of breastfeeding to reduce disparities.

PMID- 25380762
TI  - Socioeconomic position and early adolescent smoking development: evidence from
      the British Youth Panel Survey (1994-2008).
AB  - OBJECTIVE: Smoking usually develops in adolescence and is patterned by
      socioeconomic position (SEP). We examined whether early adolescent smoking
      development and associations with SEP have changed over time in a population with
      well-developed tobacco control policies. We additionally investigated the
      relative importance of socioeconomic inequalities at different stages of smoking
      development. METHODS: An annual UK rotating panel survey including data from 5122
      adolescents (51% male) aged 11-15 years between 1994 and 2008. Rates of smoking
      initiation, progression to occasional smoking (experimentation), progression to
      daily smoking (escalation), and quitting were examined using discrete-time event
      history analysis. RESULTS: Initiation, experimentation and escalation rates
      declined over the study period while quitting rates increased. Decreases in
      initiation were concentrated among older adolescents and decreases in escalation
      among those who spent a year or two as occasional smokers. Socioeconomic
      disadvantage was associated with higher rates of initiation and escalation, with
      similar findings across SEP measures. Inequalities in initiation were stronger at
      younger ages. There was less evidence of associations between SEP and quitting or
      experimentation. Inequalities in escalation remained constant over time, while
      inequalities in initiation widened before narrowing. Further modelling suggested
      that differential initiation rates contributed more to inequalities in daily
      smoking at age 15 than did differential escalation. CONCLUSIONS: Increasing
      tobacco control in the UK is associated with reduced uptake and more quitting in
      early adolescence, but socioeconomic inequalities remain. Interventions should
      focus on reducing inequalities in initiation among early adolescents.

PMID- 25380764
TI  - Identification of a novel MSH6 germline variant in a family with multiple gastro
      intestinal malignancies by next generation sequencing.
AB  - The identification of germline variants that predispose to cancer is important to
      further our understanding of tumorigenesis, guide patient management, prevent
      disease in unaffected relatives, and inform best practice for health care. We
      describe a kindred with multiple gastrointestinal malignancies where a novel MSH6
      germline susceptibility variant was identified by exome sequencing after eluding
      serial routine testing in multiple affected members. This case fosters discussion
      of our current understanding of DNA mismatch repair deficiency, the management of
      Lynch Syndrome, and the emerging role of next generation sequencing in laboratory
      medicine to identify rare pathogenic germline variants in a comprehensive,
      unbiased fashion. 

PMID- 25380763
TI  - Crystal structure of the HIV neutralizing antibody 2G12 in complex with a
      bacterial oligosaccharide analog of mammalian oligomannose.
AB  - Human immunodeficiency virus-1 (HIV-1) is a major public health threat that
      continues to infect millions of people worldwide each year. A prophylactic
      vaccine remains the most cost-effective way of globally reducing and eliminating
      the spread of the virus. The HIV envelope spike, which is the target of many
      vaccine design efforts, is densely mantled with carbohydrate and several potent
      broadly neutralizing antibodies to HIV-1 recognize carbohydrate on the envelope
      spike as a major part of their epitope. However, immunizing with recombinant
      forms of the envelope glycoprotein does not typically elicit anti-carbohydrate
      antibodies. Thus, studies of alternative antigens that may serve as a starting
      point for carbohydrate-based immunogens are of interest. Here, we present the
      crystal structure of one such anti-carbohydrate HIV neutralizing antibody (2G12)
      in complex with the carbohydrate backbone of the lipooligosaccharide from
      Rhizobium radiobacter strain Rv3, which exhibits a chemical structure that
      naturally mimics the core high-mannose carbohydrate epitope of 2G12 on HIV-1
      gp120. The structure described here provides molecular evidence of the structural
      homology between the Rv3 oligosaccharide and highly abundant carbohydrates on the
      surface of HIV-1 and raises the potential for the design of novel glycoconjugates
      that may find utility in efforts to develop immunogens for eliciting carbohydrate
      specific neutralizing antibodies to HIV. 

PMID- 25380765
TI  - Dedifferentiation of emotion regulation strategies in the aging brain.
AB  - Different emotion regulation strategies are distinctly represented in the brains
      of younger adults. Decreasing a reaction to a negative situation by
      reinterpreting it (reappraisal) relies on cognitive control regions in the
      prefrontal cortex, while distracting away from a stressor involves more posterior
      medial structures. In this study, we used Multi-Voxel pattern analyses (MVPA) to
      examine whether reappraisal and distraction strategies have distinct
      representations in the older adult brain, or whether emotion regulation
      strategies become more dedifferentiated in later life. MVPA better differentiated
      the two emotion regulation strategies for younger adults than for older adults,
      and revealed the greatest age-related differences in differentiation in the
      posterior medial cortex (PMC). Univariate analyses revealed equal PMC recruitment
      across strategies for older adults, but greater activity during distraction than
      reappraisal for younger adults. The PMC is central to self-focused processing,
      and thus our findings are consistent with the possibility that focusing on the
      self may be a default mechanism across emotion regulation strategies for older
      people. 

PMID- 25380767
TI  - Long-chain flavodoxin FldB from Escherichia coli.

PMID- 25380766
TI  - A protective effect of musical expertise on cognitive outcome following brain
      damage?
AB  - The current review examines the possibility that training-related changes that
      take place in the brains of musicians may have a beneficial effect on their
      cognitive outcome and recovery following neurological damage. First, we propose
      three different mechanisms by which training-related brain changes might result
      in relatively preserved function in musicians as compared to non-musicians with
      cerebral lesions. Next, we review the neuropsychological literature examining
      musical ability in professional musicians following brain damage, specifically of
      vascular, tumoral and epileptic aetiology. Finally, given that assessment of
      musician patients can greatly inform our understanding of the influence of
      premorbid experience on postmorbid recovery, we suggest some basic guidelines for
      the future evaluation of relevant patients. 

PMID- 25380768
TI  - Prediction of T-cell epitopes of hepatitis C virus genotype 5a.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a public health problem with almost 185
      million people estimated to be infected worldwide and is one of the leading
      causes of hepatocellular carcinoma. Currently, there is no vaccine for HCV
      infection and the current treatment does not clear the infection in all patients.
      Because of the high diversity of HCV, protective vaccines will have to overcome
      significant viral antigenic diversities. The objective of this study was to
      predict T-cell epitopes from HCV genotype 5a sequences. METHODS: HCV near full
      length protein sequences were analyzed to predict T-cell epitopes that bind human
      leukocyte antigen (HLA) class I and HLA class II in HCV genotype 5a using Propred
      I and Propred, respectively. The Antigenicity score of all the predicted epitopes
      were analysed using VaxiJen v2.0. All antigenic predicted epitopes were analysed
      for conservation using the IEDB database in comparison with 406, 221, 98, 33, 45,
      45 randomly selected sequences from each of the HCV genotypes 1a, 1b, 2, 3, 4 and
      6 respectively, downloaded from the GenBank. For epitope prediction binding to
      common HLA alleles found in South Africa, the IEDB epitope analysis tool was
      used. RESULTS: A total of 24 and 77 antigenic epitopes that bind HLA class I and
      HLA class II respectively were predicted. The highest number of HLA class I
      binding epitopes were predicted within the NS3 (63%), followed by NS5B (21%). For
      the HLA class II, the highest number of epitopes were predicted in the NS3 (30%)
      followed by the NS4B (23%) proteins. For conservation analysis, 8 and 31
      predicted epitopes were conserved in different genotypes for HLA class I and HLA
      class II alleles respectively. Several epitopes bind with high affinity for both
      HLA class I alleles and HLA class II common in South Africa. CONCLUSION: The
      predicted conserved T-cell epitopes analysed in this study will contribute
      towards the future design of HCV vaccine candidates which will avoid variation in
      genotypes, which in turn will be capable of inducing broad HCV specific immune
      responses.

PMID- 25380770
TI  - What is "severe burnout" and can its prevalence be assessed?

PMID- 25380771
TI  - Phenotyping carrot (Daucus carota L.) for yield-determining temperature response
      by calorespirometry.
AB  - MAIN CONCLUSION: Calorespirometric measurements proved to be useful for
      phenotyping temperature response in terms of optimum temperatures for growth and
      low temperature limits for growth respiration in diverse carrot genotypes. High
      and low-temperature tolerance is an important trait in many breeding programs,
      but to date, improvement strategies have had limited success. Developing new,
      cost efficient and reliable screening tools to identify and select the most
      tolerant crop plant genotypes is necessary to assist plant breeding on cold and
      heat tolerance, and calorespirometry is proposed for this. Calorespirometry is a
      technique to simultaneously measure metabolic heat rates and CO2 emission rates
      of respiring tissues and can be used as a rapid method to determine how changes
      in the environment (e.g., temperature) influence plant growth. The main aim of
      this work was, therefore, to test the usefulness of calorespirometry as a
      phenotyping tool for carrot taproot growth in response to temperature.
      Calorespirometric measurements in the carrot taproot meristems of plants from
      eight carrot inbred lines allowed identification of optimum and minimum
      temperatures for growth of plants and to distinguish between phenotypes based on
      those characteristics. The technique proved to be useful for predicting yield
      determining temperature responses in diverse carrot genotypes. Preliminary
      screening of new crop plant genotypes with calorespirometry based on their
      temperature adaptation and acclimation capability could make the screening
      process much less laborious by allowing selection of genotypes presenting the
      best growth performance under particular biotic or abiotic conditions before
      field tests.

PMID- 25380769
TI  - Common variants in the MKL1 gene confer risk of schizophrenia.
AB  - Genome-wide association studies (GWAS) of schizophrenia have identified multiple
      risk variants with robust association signals for schizophrenia. However, these
      variants could explain only a small proportion of schizophrenia heritability.
      Furthermore, the effect size of these risk variants is relatively small (eg, most
      of them had an OR less than 1.2), suggesting that additional risk variants may be
      detected when increasing sample size in analysis. Here, we report the
      identification of a genome-wide significant schizophrenia risk locus at 22q13.1
      by combining 2 large-scale schizophrenia cohort studies. Our meta-analysis
      revealed that 7 single nucleotide polymorphism (SNPs) on chromosome 22q13.1
      reached the genome-wide significance level (P < 5.0*10(-8)) in the combined
      samples (a total of 38441 individuals). Among them, SNP rs6001946 had the most
      significant association with schizophrenia (P = 2.04*10(-8)). Interestingly, all
      7 SNPs are in high linkage disequilibrium and located in the MKL1 gene.
      Expression analysis showed that MKL1 is highly expressed in human and mouse
      brains. We further investigated functional links between MKL1 and proteins
      encoded by other schizophrenia susceptibility genes in the whole human protein
      interaction network. We found that MKL1 physically interacts with GSK3B, a
      protein encoded by a well-characterized schizophrenia susceptibility gene.
      Collectively, our results revealed that genetic variants in MKL1 might confer
      risk to schizophrenia. Further investigation of the roles of MKL1 in the
      pathogenesis of schizophrenia is warranted. 

PMID- 25380772
TI  - New radiographic parameter assessing hindfoot alignment in stage II adult
      acquired flatfoot deformity.
AB  - BACKGROUND: The hindfoot moment arm is a reliable measurement of hindfoot valgus
      deformity in stage II adult-acquired flatfoot deformity (AAFD) and can be used to
      guide intraoperative correction of the hindfoot. There is currently little
      understanding of how the hindfoot moment arm relates to angular measurements of
      hindfoot alignment. The purpose of this study was to develop a new hindfoot
      alignment angle that can reliably quantify hindfoot valgus in patients with AAFD
      and to establish the relationship of this angle with the hindfoot moment arm.
      METHODS: Preoperative hindfoot alignment radiographs were reviewed for 10
      consecutive patients (10 feet) who were indicated for reconstruction for stage II
      AAFD. A second group of 10 patients (10 feet) without flatfoot were identified to
      serve as normal controls. The hindfoot moment arm and the new hindfoot alignment
      angle were measured in blinded fashion by 2 readers. Reliability was assessed
      using intraclass correlation coefficients (ICCs). The difference in angle between
      normal and flatfoot patients was assessed with a Mann-Whitney U test. A linear
      regression model was used to assess the relationship between hindfoot moment arm
      and the new hindfoot alignment angle. RESULTS: Intra- and interrater reliability
      for the hindfoot alignment angle was excellent (ICC = 0.979 and 0.965,
      respectively). Flatfoot patients had greater mean angles than did normal patients
      (22.5 +/- 4.9 vs 5.6 +/- 5.4 degrees, P < .001). The hindfoot moment arm was
      correlated significantly with the hindfoot alignment angle (P < .001), increasing
      by 0.81 mm for every degree increase in angle (adjusted R (2) = 0.9046).
      CONCLUSION: These results indicate that the new hindfoot alignment angle is a
      reliable measure of hindfoot valgus and can differentiate between flatfoot and
      normal patients. In addition, the strong linear relationship between the hindfoot
      alignment angle and moment arm may allow for the use of this angle in the
      intraoperative correction of hindfoot valgus. LEVEL OF EVIDENCE: Level III,
      retrospective case control study.

PMID- 25380773
TI  - Sagittal subtalar and talocrural joint assessment with weight-bearing fluoroscopy
      during barefoot ambulation.
AB  - BACKGROUND: Identifying talar position during ambulation has proved difficult as
      the talus lacks palpable landmarks for skin marker placement and more invasive
      methodologies such as bone pins are not practical for most clinical subjects. A
      fluoroscopic motion system was used to track the talus and calcaneus, allowing
      kinematic analysis of the talocrural and subtalar joints. METHODS: Thirteen male
      subjects (mean age 22.9 +/- 3.0 years) previously screened for normal gait were
      tested. A fluoroscopy unit was used to collect images at 120 fps during stance.
      Sagittal motion of the talocrural and subtalar joints were analyzed. RESULTS: The
      intersubject mean and standard deviation values for all 58 trials of 13 subjects
      are reported. Maximum talocrural joint plantarflexion of 11.2 degrees (4.3
      degrees of standard deviation) occurred at 11% stance and maximum dorsiflexion of
      -6.9 degrees (5.6 degrees of standard deviation) occurred at 85%. Maximum
      subtalar joint plantarflexion of 4.8 degrees (1.0 degrees of standard deviation)
      occurred at 96% stance and maximum dorsiflexion of -3.6 degrees (2.3 degrees of
      standard deviation) occurred at 30%. Talocrural and subtalar range of motion
      values during stance were 18.1 and 8.4 degrees, respectively. CONCLUSION:
      Existing fluoroscopic technology was capable of defining sagittal plane
      talocrural and subtalar motion during gait. These kinematic results compare
      favorably with more invasive techniques. This type of assessment could support
      more routine analysis of in vivo bony motion during gait. CLINICAL RELEVANCE:
      Fluoroscopic technology offers improved sagittal plane motion evaluation during
      weight-bearing with potential application in patients with end-stage ankle
      arthritis, postoperative ankle replacements and fusions, and orthotics and
      braces.

PMID- 25380774
TI  - Biomechanical evaluation of varying the number of loops in a repair of a
      physiological model of Achilles tendon rupture.
AB  - BACKGROUND: Numerous suturing techniques have been described to treat Achilles
      tendon ruptures. No prior studies have evaluated frayed tendon ends on construct
      strength and whether this allows for less extensile exposure. METHODS: Forty
      bovine Achilles tendons were divided into groups: 1 control and 4 experimental.
      Experimental groups were sectioned with ends frayed longitudinally in 2 mm
      intervals for 2 cm with no fraying for the control group. Four-stand Krackow
      sutures were used for repairs with 3 loops in the control group, 2 loops in
      frayed section for experimental groups, and varying numbers of loops (1-4) in
      healthy tendon. Samples were tested in loading cells at 100 N and 190 N for 1000
      cycles. Gap width and maximum load failure were measured. RESULTS: Gapping was <5
      mm in controls at 100 N-190 N, significantly lower than experimentals. Greatest
      gapping occurred in groups with 1-2 loops in healthy tendon (10.9-13.9 mm). Most
      early catastrophic failures (5/8) occurred in groups with 1-2 loops in healthy
      tendon. Two failures at 100 N occurred in 1-loop healthy tendons. The least
      failures occurred in controls (2/8), at 190 N. CONCLUSION: Suture loops
      incorporated into frayed tendon portions predisposed repairs to significantly
      greater gapping and lower maximal failure forces than 4-strand Krackow repairs in
      unfrayed tendons. CLINICAL RELEVANCE: We cannot recommend attempting more limited
      exposures with sutures in frayed tendon as this may lead to early repair failure.
      We provided a physiologic model utilizing frayed tendon ends that resembles in
      vivo Achilles tendon rupture.

PMID- 25380775
TI  - Assessment of coronal plane subtalar joint alignment in peritalar subluxation via
      weight-bearing multiplanar imaging.
AB  - BACKGROUND: Patients with adult-acquired flatfoot deformity (AAFD) develop
      peritalar subluxation, which may stem from valgus inclination of the inferior
      surface of the talus. We hypothesized that patients with AAFD would have an
      increased valgus tilt of the subtalar joint in the coronal plane compared to
      controls when assessed with a novel multiplanar weight-bearing imaging (MP-WB).
      METHODS: Eighteen normal and 36 stage II AAFD patients scheduled to undergo
      operative reconstruction were evaluated by MP-WB through measuring 3 novel angles
      of the subtalar joint in the coronal view: (1) angle between inferior facet of
      the talus and the horizontal/floor (inftal-hor), (2) angle between inferior and
      superior facets of the talus (inftal-suptal), and (3) angle between inferior
      facet of the talus and superior facet of the calcaneus (inftal-supcal). Intra-
      and interobserver reliability were evaluated via intraclass correlation
      coefficients (ICCs). Differences in angles between AAFD patients and controls
      were evaluated using Wilcoxon rank-sum test. RESULTS: Intra- and interobserver
      reliability were excellent for inftal-hor (ICC .942 and .991, respectively) and
      inftal-suptal (ICC .948 and .989, respectively), and moderate-good for inftal
      supcal (ICC .604 and .742, respectively). Inftal-hor and inftal-suptal angles
      were found to be significantly greater in AAFD patients (P < 0.001) at all 3
      locations along the posterior subtalar joint, while inftal-supcal did not
      demonstrate a significant difference (P = .741). While controls exhibited varus
      orientation at the anterior aspect of the joint, AAFD patients maintained a
      valgus orientation throughout. CONCLUSION: Inftal-hor and inftal-suptal angles
      provided a reliable means of evaluating the orientation of the subtalar joint
      axis in AAFD via MP-WB, and showed that the subtalar joint had increased valgus
      orientation in AAFD compared to controls. This may allow for identification of
      patients at risk for developing AAFD, and could potentially be used in guiding
      operative reconstruction.

PMID- 25380776
TI  - Joseph E. Campana (1952-2014).

PMID- 25380777
TI  - XMS: cross-platform normalization method for multimodal mass spectrometric tissue
      profiling.
AB  - Here we present a proof of concept cross-platform normalization approach to
      convert raw mass spectra acquired by distinct desorption ionization methods
      and/or instrumental setups to cross-platform normalized analyte profiles. The
      initial step of the workflow is database driven peak annotation followed by
      summarization of peak intensities of different ions from the same molecule. The
      resulting compound-intensity spectra are adjusted to a method-independent
      intensity scale by using predetermined, compound-specific normalization factors.
      The method is based on the assumption that distinct MS-based platforms capture a
      similar set of chemical species in a biological sample, though these species may
      exhibit platform-specific molecular ion intensity distribution patterns. The
      method was validated on two sample sets of (1) porcine tissue analyzed by laser
      desorption ionization (LDI), desorption electrospray ionization (DESI), and rapid
      evaporative ionization mass spectrometric (REIMS) in combination with Fourier
      transformation-based mass spectrometry; and (2) healthy/cancerous colorectal
      tissue analyzed by DESI and REIMS with the latter being combined with time-of
      flight mass spectrometry. We demonstrate the capacity of our method to reduce MS
      platform specific variation resulting in (1) high inter-platform concordance
      coefficients of analyte intensities; (2) clear principal component based
      clustering of analyte profiles according to histological tissue types,
      irrespective of the used desorption ionization technique or mass spectrometer;
      and (3) accurate "blind" classification of histologic tissue types using cross
      platform normalized analyte profiles. 

PMID- 25380778
TI  - A Web-based database of genetic association studies in cutaneous melanoma
      enhanced with network-driven data exploration tools.
AB  - The publicly available online database MelGene provides a comprehensive,
      regularly updated, collection of data from genetic association studies in
      cutaneous melanoma (CM), including random-effects meta-analysis results of all
      eligible polymorphisms. The updated database version includes data from 192
      publications with information on 1114 significantly associated polymorphisms
      across 280 genes, along with new front-end and back-end capabilities. Various
      types of relationships between data are calculated and visualized as networks. We
      constructed 13 different networks containing the polymorphisms and the genes
      included in MelGene. We explored the derived network representations under the
      following questions: (i) are there nodes that deserve consideration regarding
      their network connectivity characteristics? (ii) What is the relation of either
      the genome-wide or nominally significant CM polymorphisms/genes with the ones
      highlighted by the network representation? We show that our network approach
      using the MelGene data reveals connections between statistically significant
      genes/ polymorphisms and other genes/polymorphisms acting as 'hubs' in the
      reconstructed networks. To the best of our knowledge, this is the first database
      containing data from a comprehensive field synopsis and systematic meta-analyses
      of genetic polymorphisms in CM that provides user-friendly tools for in-depth
      molecular network visualization and exploration. The proposed network connections
      highlight potentially new loci requiring further investigation of their relation
      to melanoma risk. Database URL: http://www.melgene.org. 

PMID- 25380779
TI  - PolyprOnline: polyproline helix II and secondary structure assignment database.
AB  - The polyproline helix type II (PPII) is a regular protein secondary structure
      with remarkable features. Many studies have highlighted different crucial
      biological roles supported by this local conformation, e.g. in the interactions
      between biological macromolecules. Although PPII is less frequently present than
      regular secondary structures such as canonical alpha helices and beta strands, it
      corresponds to 3-10% of residues. Up to now, PPII is not assigned by most popular
      assignment tools, and therefore, remains insufficiently studied. PolyprOnline
      database is, therefore, dedicated to PPII structure assignment and analysis to
      facilitate the study of PPII structure and functional roles. This database is
      freely accessible from www.dsimb.inserm.fr/dsimb_tools/polyproline. 

PMID- 25380780
TI  - VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and
      their targets.
AB  - Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to
      benefit the virus. Hence, miRNAs play a key role in host-virus interactions and
      pathogenesis of viral diseases. Lately, miRNAs have also shown potential as
      important targets for the development of novel antiviral therapeutics. Although
      several miRNA and their target repositories are available for human and other
      organisms in literature, but a dedicated resource on viral miRNAs and their
      targets are lacking. Therefore, we have developed a comprehensive viral miRNA
      resource harboring information of 9133 entries in three subdatabases. This
      includes 1308 experimentally validated miRNA sequences with their isomiRs encoded
      by 44 viruses in viral miRNA ' VIRMIRNA: ' and 7283 of their target genes in '
      VIRMIRTAR': . Additionally, there is information of 542 antiviral miRNAs encoded
      by the host against 24 viruses in antiviral miRNA ' AVIRMIR': . The web interface
      was developed using Linux-Apache-MySQL-PHP (LAMP) software bundle. User-friendly
      browse, search, advanced search and useful analysis tools are also provided on
      the web interface. VIRmiRNA is the first specialized resource of experimentally
      proven virus-encoded miRNAs and their associated targets. This database would
      enhance the understanding of viral/host gene regulation and may also prove
      beneficial in the development of antiviral therapeutics. Database URL:
      http://crdd.osdd.net/servers/virmirna. 

PMID- 25380781
TI  - ChloroSSRdb: a repository of perfect and imperfect chloroplastic simple sequence
      repeats (cpSSRs) of green plants.
AB  - Simple sequence repeats (SSRs) are regions in DNA sequence that contain repeating
      motifs of length 1-6 nucleotides. These repeats are ubiquitously present and are
      found in both coding and non-coding regions of genome. A total of 534 complete
      chloroplast genome sequences (as on 18 September 2014) of Viridiplantae are
      available at NCBI organelle genome resource. It provides opportunity to mine
      these genomes for the detection of SSRs and store them in the form of a database.
      In an attempt to properly manage and retrieve chloroplastic SSRs, we designed
      ChloroSSRdb which is a relational database developed using SQL server 2008 and
      accessed through ASP.NET. It provides information of all the three types
      (perfect, imperfect and compound) of SSRs. At present, ChloroSSRdb contains 124
      430 mined SSRs, with majority lying in non-coding region. Out of these, PCR
      primers were designed for 118 249 SSRs. Tetranucleotide repeats (47 079) were
      found to be the most frequent repeat type, whereas hexanucleotide repeats (6414)
      being the least abundant. Additionally, in each species statistical analyses were
      performed to calculate relative frequency, correlation coefficient and chi-square
      statistics of perfect and imperfect SSRs. In accordance with the growing interest
      in SSR studies, ChloroSSRdb will prove to be a useful resource in developing
      genetic markers, phylogenetic analysis, genetic mapping, etc. Moreover, it will
      serve as a ready reference for mined SSRs in available chloroplast genomes of
      green plants. Database URL: www.compubio.in/chlorossrdb/ 

PMID- 25380782
TI  - The Virtual Xenbase: transitioning an online bioinformatics resource to a private
      cloud.
AB  - As a model organism database, Xenbase has been providing informatics and genomic
      data on Xenopus (Silurana) tropicalis and Xenopus laevis frogs for more than a
      decade. The Xenbase database contains curated, as well as community-contributed
      and automatically harvested literature, gene and genomic data. A GBrowse genome
      browser, a BLAST+ server and stock center support are available on the site. When
      this resource was first built, all software services and components in Xenbase
      ran on a single physical server, with inherent reliability, scalability and inter
      dependence issues. Recent advances in networking and virtualization techniques
      allowed us to move Xenbase to a virtual environment, and more specifically to a
      private cloud. To do so we decoupled the different software services and
      components, such that each would run on a different virtual machine. In the
      process, we also upgraded many of the components. The resulting system is faster
      and more reliable. System maintenance is easier, as individual virtual machines
      can now be updated, backed up and changed independently. We are also experiencing
      more effective resource allocation and utilization. Database URL:
      www.xenbase.org. 

PMID- 25380783
TI  - Postpartum depression screening by telephone: a good alternative for public
      health and research.
AB  - This study verified the reliability and validity of the Edinburg Postpartum
      Depression Scale (EPDS) administered by telephone interviews. In a cross
      sectional study of a cohort from Brazil (BRISA), the EPDS was administered by
      telephone to 1,083 women within 12 months postpartum, and 257 (23.7 %)
      participants had an EPDS score >=10. At 67 +/- 48 days after their telephone
      interview, 199 (EPDS >=10 = 96; EPDS <10 = 103) participants were interviewed
      face-to-face using the Structured Clinical Interview for DSM-IV (SCID) and
      completed the EPDS again by self-report. In 90 participants, the diagnosis of
      major depressive episode was confirmed by the SCID (EPDS >=10 = 65; EPDS <10 =
      25). The Cronbach's alpha coefficient was 0.861. The Spearman's correlation
      between the EPDS administered by telephone and the self-reported EPDS was 0.69 (p
      < 0.001). The receiver-operating characteristic (ROC) curve for the EPDS
      administered by telephone was 0.78 (95 % confidence interval (CI) = 0.72 to
      0.84). Scores >=10 showed a sensitivity of 72.2 %, a specificity of 71.6 %, and a
      positive predictive value of 67.7 %. The application of the EPDS by telephone is
      a suitable alternative for clinical practice and research and represents a method
      to optimize the diagnosis of postpartum depression. 

PMID- 25380784
TI  - Childhood sexual abuse and posttraumatic stress disorder among pregnant and
      postpartum women: review of the literature.
AB  - The aims of this review are (i) to summarize and evaluate current knowledge on
      the association between childhood sexual abuse (CSA) and posttraumatic stress
      disorder (PTSD) in pregnant and postpartum women, (ii) to provide suggestions for
      future research on this topic, and (iii) to highlight some clinical implications.
      Relevant publications were identified through literature searches of four
      databases (PubMed, Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), PsycINFO, and PsycARTICLES) using keywords such as "child abuse,"
      "posttraumatic stress," "pregnancy," and "postpartum". Five studies were included
      in this review. Findings across all studies were consistent with higher
      prevalence of PTSD diagnosis or symptomatology among women with history of CSA.
      However, only findings from two studies were statistically significant. One study
      observed higher overall PTSD scores in women with CSA history compared to women
      with non-CSA trauma history or no trauma history during pregnancy (mean +/- SD
      1.47 (0.51) vs. 1.33 (0.41) vs. 1.22 (0.29), p < 0.001), at 2 months postpartum
      (mean +/- SD 1.43 (0.49) vs. 1.26 (0.38) vs. 1.19 (0.35), p < 0.001), and at 6
      months postpartum (mean +/- SD 1.36 (1.43) vs. 1.20 (0.33) vs. 1.14 (0.27), p <
      0.001). Another study observed that the prevalence of PTSD during pregnancy was
      4.1 % in women with no history of physical or sexual abuse, 11.4 % in women with
      adult physical or sexual abuse history, 16.0 % in women with childhood physical
      or sexual abuse history, and 39.0 % in women exposed to both childhood and adult
      physical or sexual abuse (p < 0.001); in a subsequent analysis, the investigators
      reported that pregnant women with PTSD had over 5-fold odds of having a history
      of childhood completed rape compared to counterparts without PTSD (OR = 5.3, 95 %
      CI 3.2, 8.7). Overall, available evidence suggests positive associations of CSA
      with clinical PTSD or PTSD symptomatology among pregnant and postpartum women.

PMID- 25380785
TI  - Application of a deformable registration technique to investigate breath-hold
      reproducibility.
AB  - PURPOSE: To develop an objective and less invasive method for evaluating breath
      hold status, and to investigate breath-hold reproducibility during voluntary
      breath-holding irradiation. MATERIALS AND METHODS: We enrolled 20 patients who
      were treated using a voluntary breath-holding technique. Four or five sessions of
      cone beam computed tomography (CT) were performed during the radiotherapy
      session. An image of the lung with respiratory tract was extracted from the CT
      findings. The rigid registration of subsequent CT findings was completed using
      the first fraction CT findings. Next, subsequent CT images already subjected to
      rigid registration were deformed using the first CT images. We compared the
      differences in the subsequent CT images before and after the deformable
      registration. RESULTS: We were able to complete the method to evaluate breath
      hold status without having to consider set-up uncertainty, manual processes,
      visual estimates, or excessive patient cooperation. Tumor dislocation was almost
      within 3 mm in all directions and deformation was much smaller than 30 % period
      of free breathing. CONCLUSION: This method we have developed may have great
      potential for the objective verification of breath-hold reproducibility in a less
      invasive manner. This method assumed that the voluntary breath-hold status was
      reproducible enough at a clinically satisfactory level.

PMID- 25380786
TI  - Effectiveness of CT assists for intraarterial chemotherapy: therapeutic outcome
      of chemoradiation for advanced head and neck cancer extending across the
      anatomical midline.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of CT
      assist for intraarterial chemotherapy in relation to the therapeutic outcomes of
      intraarterial chemoradiation for advanced head and neck cancer with extension
      across the anatomical midline (EAM). METHODS: This retrospective study evaluated
      64 consecutive patients. In total, 26 and 38 patients had cancer with or without
      EAM, respectively. These patients underwent an intraarterial cisplatin infusion
      (200 mg/m(2), days 1 and 35) and intravenous 5-FU infusion (800 mg/m(2), days 1-5
      and 36-39) concomitantly with radiotherapy. Angiography-assisted CT was performed
      to confirm complete coverage during the intraarterial chemotherapy. The accuracy
      of diagnosing tumor vessels by digital subtraction angiography (DSA) was
      evaluated using receiver-operating characteristic analysis by two radiologists.
      The overall survival and locoregional control rates were calculated by the Kaplan
      Meier method. RESULTS: DSA was not useful for diagnosing tumor vessels. The 2
      year overall survival rates for the patients with cancer with or without EAM were
      83 and 90 %, while the 2-year locoregional control rates were 95 and 82 %,
      respectively. Locoregional control or the overall survival rates showed no
      significant differences. CONCLUSIONS: Intraarterial chemotherapy using
      angiography-assisted CT during chemoradiation therapy can achieve comparable
      therapeutic outcomes for cancer with and without EAM.

PMID- 25380787
TI  - Psychocultural Correlates of Mental Health Service Utilization Among African
      American and European American Girls.
AB  - Structural equation modeling was used to examine the effects of cultural factors
      (ethnic identity, perceived discrimination), family relations, and child problem
      type on mental health service utilization in a community sample of 1,480
      adolescent girls (860 African American, 620 European American) between ages 15
      and 17 years enrolled in the Pittsburgh Girls Study. Results revealed ethnic
      identity, caregiver attachment, and conduct disorder were related to service use
      among African American girls. Among European American girls, correlate patterns
      differed by clinical need. Findings highlight the need for research on health
      disparities to examine racially specific influences on service utilization.

PMID- 25380788
TI  - Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis
      in the CKiD cohort.
AB  - BACKGROUND: Hepcidin, a key iron regulatory protein, is elevated in patients with
      chronic kidney disease (CKD). Its role in the development and progression of the
      anemia of CKD in children remains poorly defined. METHODS: Cross-sectional and
      longitudinal study in children aged 1-16 years with stage 2-4 CKD in the Chronic
      Kidney Disease in Children (CKiD) cohort (n = 133) with hepcidin measured at
      baseline and hemoglobin (HGB) measured annually at follow-up. Anemia was defined
      as HGB <5th percentile for age/sex OR treatment with an erythropoiesis
      stimulating agent (ESA). RESULTS: Hepcidin levels correlated negatively with
      glomerular filtration rate (GFR; r = -0.22, p = 0.01) and positively with
      ferritin (r = 0.67, p < 0.001). At the lower end of the GFR spectrum at baseline
      (10th percentile, 27.5 mL/min/1.73 m(2)), higher hepcidin was associated with a
      0.87 g/dL decrease in HGB during follow-up (95 % CI -1.69, -0.05 g/dL, p =
      0.038). At higher GFR percentiles there was no significant association between
      baseline hepcidin and HGB during follow-up. Among 90 non-anemic subjects at
      baseline, 23.3 % developed incident anemia. In subjects with GFR  <=  the median,
      a higher hepcidin level was associated with an increased risk of incident anemia
      (at the 10th percentile GFR, HR 3.471, 95 % CI 1.228, 9.810, p = 0.019; at the
      25th percentile GFR, HR 2.641, 95 % CI 1.213, 5.750, p = 0.014; at the 50th
      percentile GFR, HR 1.953, 95 % CI 1.011, 3.772, p = 0.046). Among subjects with
      GFR at the 75th percentile or above, incrementally higher baseline hepcidin was
      not associated with increased anemia risk. CONCLUSIONS: Higher hepcidin levels
      are associated with a decreased HGB and an increased risk of incident anemia, and
      this association is most significant among subjects with lower GFR.

PMID- 25380789
TI  - Does obesity or hyperuricemia influence lithogenic risk profile in children with
      urolithiasis?
AB  - BACKGROUND: There are indications that obesity and hyperuricemia may influence
      the formation and composition of urinary stones. The aim of our study was to
      determine the effect of obesity and hyperuricemia on the urinary lithogenic risk
      profile in a large cohort of pediatric patients. METHODS: The study population
      comprised 478 children with urolithiasis and 517 healthy children (reference
      group). We studied the effects of obesity on the lithogenic profile by dividing
      the patients with urolithiasis into two groups based on body mass index Z-score
      (patients who were overweight/obese vs. those with normal weight for age) and
      comparing the two groups. To study the effect of hyperuricemia on the lithogenic
      profile, we divided the patients with urolithiasis into two groups based on the
      presence or not of hyperuricemia (110 patients with urolithiasis accompanied by
      hyperuricemia vs. 368 patients with urolithiasis and normal serum uric acid
      levels) and compared the groups. RESULTS: Among the children and adolescents with
      urolithiasis and hyperuricemia, there was a significantly lower excretion of
      crystallization inhibitors (citrates, magnesium). We also found significantly
      negative correlations between serum uric acid levels and the urine
      citrate/creatinine ratio (citrate/cr.; r = -0.30, p < 0.01), as well as the
      magnesium/cr. ratio (Mg/cr.; r = -0.33, p < 0.01). There was no statistically
      significant differences in the urinary excretion of oxalates, citrates, calcium,
      phosphorus, magnesium and uric acid between children with urolithiasis who were
      either overweight or obese and children with urolithiasis who had a normal body
      weight. CONCLUSIONS: In our pediatric patient cohort, hyperuricemia was
      associated with a decrease in the excretion of crystallization inhibitors in the
      urine, but the clinical relevance of this observation needs to be confirmed in
      future studies. Obesity and overweight had no direct influence on the lithogenic
      risk profile in the urinary stone formers in our study, but there was an
      indication that higher serum uric acid may be associated with impairment in renal
      function, which in turn could influence the excretion of lithogenic parameters.

PMID- 25380790
TI  - Kinetic modelling for the assay of nortriptyline hydrochloride using potassium
      permanganate as oxidant.
AB  - Kinetic methods for accurate determination of nortriptyline hydrochloride have
      been described. The methods are based on the oxidation of nortriptyline
      hydrochloride with KMnO4 in acidic and basic media. In acidic medium, the
      decrease in absorbance at 525.5 nm and in basic medium, the increase in
      absorbance at 608.5 nm were measured as a function of time. The variables
      affecting the reactions were carefully investigated and optimised. Kinetic models
      such as initial rate, rate constant, variable time and fixed time were employed
      to construct the calibration curves. The initial rate and fixed time methods were
      selected for quantification of nortriptyline hydrochloride. In acidic medium, the
      calibration curves showed a linear response over the concentration range 10-50
      MUg mL(-1) for initial rate and 10-60 MUg mL(-1) for fixed time method (2 min).
      In basic medium, the calibration graphs were linear over the concentration range
      10-100 MUg mL(-1) for initial rate and fixed time methods (4 min). In acidic
      medium, the limits of detection for initial rate and fixed time methods (2 min)
      were 1.02 and 3.26 MUg mL(-1), respectively. In basic medium, the limits of
      detection were found to be 1.67 and 1.55 MUg mL(-1) for initial rate and fixed
      time methods (4 min), respectively. The initial rate and fixed time methods have
      been successfully applied to the determination of nortriptyline hydrochloride in
      commercial dosage form. Statistical comparison of the results of the proposed
      methods with those of reference method exhibited excellent agreement and there is
      no significant difference between the compared methods in terms of accuracy and
      precision. 

PMID- 25380791
TI  - Adaptation to hot environmental conditions: an exploration of the performance
      basis, procedures and future directions to optimise opportunities for elite
      athletes.
AB  - Extreme environmental conditions present athletes with diverse challenges;
      however, not all sporting events are limited by thermoregulatory parameters. The
      purpose of this leading article is to identify specific instances where hot
      environmental conditions either compromise or augment performance and, where heat
      acclimation appears justified, evaluate the effectiveness of pre-event
      acclimation processes. To identify events likely to be receptive to pre
      competition heat adaptation protocols, we clustered and quantified the magnitude
      of difference in performance of elite athletes competing in International
      Association of Athletics Federations (IAAF) World Championships (1999-2011) in
      hot environments (>25  degrees C) with those in cooler temperate conditions (<25 
      degrees C). Athletes in endurance events performed worse in hot conditions (~3 %
      reduction in performance, Cohen's d > 0.8; large impairment), while in contrast,
      performance in short-duration sprint events was augmented in the heat compared
      with temperate conditions (~1 % improvement, Cohen's d > 0.8; large performance
      gain). As endurance events were identified as compromised by the heat, we
      evaluated common short-term heat acclimation (<=7 days, STHA) and medium-term
      heat acclimation (8-14 days, MTHA) protocols. This process identified beneficial
      effects of heat acclimation on performance using both STHA (2.4 +/- 3.5 %) and
      MTHA protocols (10.2 +/- 14.0 %). These effects were differentially greater for
      MTHA, which also demonstrated larger reductions in both endpoint exercise heart
      rate (STHA: -3.5 +/- 1.8 % vs MTHA: -7.0 +/- 1.9 %) and endpoint core temperature
      (STHA: -0.7 +/- 0.7 % vs -0.8 +/- 0.3 %). It appears that worthwhile acclimation
      is achievable for endurance athletes via both short-and medium-length protocols
      but more is gained using MTHA. Conversely, it is also conceivable that heat
      acclimation may be counterproductive for sprinters. As high-performance athletes
      are often time-poor, shorter duration protocols may be of practical preference
      for endurance athletes where satisfactory outcomes can be achieved.

PMID- 25380792
TI  - Use of thermography to monitor sole haemorrhages and temperature distribution
      over the claws of dairy cattle.
AB  - Subclinical laminitis, an early pathological event in the development of many
      claw diseases, is an important factor in the welfare and economics of high
      producing dairy cows. However, the aetiology and pathogenesis of this complex
      claw disease are not well understood. The present study investigated to what
      extent thermographic examination of claws is able to give information about
      corium inflammation, and whether the technique may be used as a diagnostic tool
      for early detection of subclinical laminitis. Moreover, the temperature
      distribution over the individual main claws was investigated to obtain further
      knowledge about pressure distribution on the claws. For this purpose the claws of
      123 cows were evaluated in the first week after calving as well as after the
      second month of lactation for presence of sole haemorrhages (a sign of
      subclinical laminitis). Furthermore, the ground contact area was analysed by
      thermography. Sole haemorrhages were significantly increased by the second month
      of lactation. Thermography showed clear differences between the claws of the
      front limbs and hindlimbs, as well as between lateral and medial claws. Although
      the distribution of sole haemorrhages was consistent with the pattern of the
      temperature distribution over the main claws, no clear correlation was found
      between the claw temperature after calving and the visible laminitis-like changes
      (sole haemorrhages) eight weeks later. 

PMID- 25380793
TI  - Primary prevention of lead poisoning in children: a cross-sectional study to
      evaluate state specific lead-based paint risk reduction laws in preventing lead
      poisoning in children.
AB  - BACKGROUND: Children younger than 72 months are most at risk of environmental
      exposure to lead from ingestion through normal mouthing behavior. Young children
      are more vulnerable to lead poisoning than adults because lead is absorbed more
      readily in a child's gastrointestinal tract. Our focus in this study was to
      determine the extent to which state mandated lead laws have helped decrease the
      number of new cases of elevated blood-lead levels (EBLL) in homes where an index
      case had been identified. METHODS: A cross-sectional study was conducted to
      compare 682 residential addresses, identified between 2000 and 2009, in two
      states with and one state without laws to prevent childhood lead poisoning among
      children younger than 72 months, to determine whether the laws were effective in
      preventing subsequent cases of lead poisoning detected in residential addresses
      after the identification of an index case. In this study, childhood lead
      poisoning was defined as the blood lead level (BLL) that would have triggered an
      environmental investigation in the residence. The two states with lead laws,
      Massachusetts (MA) and Ohio (OH), had trigger levels of >=25 MUg/dL and >=15
      MUg/dL respectively. In Mississippi (MS), the state without legislation, the
      trigger level was >=15 MUg/dL. RESULTS: The two states with lead laws, MA and OH,
      were 79% less likely than the one without legislation, MS, to have residential
      addresses with subsequent lead poisoning cases among children younger than 72
      months, adjusted OR = 0.21, 95% CI (0.08-0.54). CONCLUSIONS: For the three states
      studied, the evidence suggests that lead laws such as those studied herein
      effectively reduced primary exposure to lead among young children living in
      residential addresses that may have had lead contaminants.

PMID- 25380795
TI  - Use of probiotics to reduce faecal shedding of Shiga toxin-producing Escherichia
      coli in sheep.
AB  - Shiga toxin-producing Escherichia coli (STEC) are zoonotic, foodborne pathogens
      of humans. Ruminants, including sheep, are the primary reservoirs of STEC and
      there is a need to develop intervention strategies to reduce the entry of STEC
      into the food chain. The initiation of the majority of bacterial, enteric
      infections involves colonisation of the gut mucosal surface by the pathogen.
      However, probiotic bacteria can serve to decrease the severity of infection via a
      number of mechanisms including competition for receptors and nutrients, and/or
      the synthesis of organic acids and bacteriocins that create an environment
      unfavourable for pathogen development. The aim of the current study was to
      determine whether the administration of a probiotic mixture to sheep
      experimentally infected with a non-O157 STEC strain, carrying stx1, stx2 and eae
      genes, was able to decrease faecal shedding of the pathogen. The probiotic
      mixture contained Lactobacillus acidophilus, Lactobacillus helveticus,
      Lactobacillus bulgaricus, Lactobacillus lactis, Streptococcus thermophilus and
      Enterococcus faecium. The numbers of non-O157 STEC in faecal samples collected
      from sheep receiving daily doses of the probiotic mixture were significantly
      lower at the 3rd, 5th and 6th week post-inoculation when compared to the levels
      recorded in untreated animals. It was concluded that administration of the
      probiotic mixture reduced faecal shedding of non-O157 STEC in sheep, and holds
      potential as a pre-harvest intervention method to reduce transmission to humans. 

PMID- 25380794
TI  - [Acute perioperative hemodilution without using hydroxyethyl starch : hemodynamic
      alterations under "controlled" hypovolemia].
AB  - BACKGROUND: Up to now hydroxyethyl starch preparations have frequently been used
      to compensate for volume deficits accompanying blood withdrawal during acute
      normovolemic hemodilution. This approach was questioned with respect to the
      current limitations for use of hydroxyethyl starch solutions imposed by the
      European Medicines Agency. Because crystalloids distribute evenly across the
      whole extracellular compartment, 80 % of the infused solution will be "lost" to
      the interstitial space. Thus, a physiological adjustment of blood loss caused by
      hemodilution with crystalloids alone (1:5 ratio) seems hardly feasible and
      according to current data perhaps not even desirable. A 3:1 ratio (crystalloids
      versus blood loss) as applied in the current study can be regarded as a practical
      compromise between physiological needs and recommendations according to the
      literature (1.4:1) but will lead to moderate hypovolemia the hemodynamic
      consequences of which are not well described. AIM: The current study investigates
      the hemodynamic impact of a hemodilution with crystalloids under the precondition
      of a 3:1 substitution ratio compared to withdrawn blood. METHODS: In the context
      of acute perioperative hemodilution 10 otherwise healthy women graded I and II on
      the American Society of Anesthesiologists (ASA) classification scheduled for open
      gynecological cancer surgery underwent an average blood withdrawal of 1097 +/-
      285 ml which was substituted by an average of 3430 +/- 806 ml of Ringer's
      lactate. The resulting deficit in blood volume was exactly quantified by a double
      tracer technique. Hemodynamic changes were evaluated by a combination of
      thermodilution and pulse contour analysis (PiCCO system(r)). Subsequently, the
      remaining volume deficit was compensated by 245 +/- 64 ml of a 20 % albumin
      solution and hemodynamic parameters were again evaluated. RESULTS: When infusing
      Ringer's lactate in a 3:1 ratio compared to the actual blood loss, the blood
      volume decreased by 12 %. The volume effect of Ringer's lactate proved to be 17
      %. While mean arterial pressure and heart rate remained constant, key hemodynamic
      parameters changed relevantly during the time course. A significant rise in
      cardiac output and myocardial contractility could be observed which was
      accompanied by a decrease in systemic vascular resistance. In contrast, cardiac
      preload and the parameters representing pulmonary vascular permeability remained
      unaltered. The infusion of 245 +/- 64 ml of a 20 % albumin solution nearly
      completely restituted blood volume and led to an insignificant rise in systemic
      vascular resistance but did not normalize cardiac output or myocardial
      contractility. CONCLUSION: In the study population, the loss of intravascular
      fluid during perioperative haemodilution could be compensated by an increase in
      cardiac performance. However, whether patients with a reduced cardiac capacity
      (i.e. older patients) are capable to improve their cardiac output sufficiently in
      order to compensate hypovolemia accompanying perioperative haemodilution with
      crystalloids remains questionable.

PMID- 25380797
TI  - Impact of a probiotic, inulin, or their combination on the piglets' microbiota at
      different intestinal locations.
AB  - Natural feed additives are used to maintain health and to promote performance of
      pigs without antibiotics. Effects of a probiotic, inulin, and their combination
      (synbiotic), on the microbial diversity and composition at different intestinal
      locations were analysed using denaturing gradient gel electrophoresis (DGGE),
      real-time PCR, and 16S rRNA gene pyrosequencing. Bacterial diversity assessed by
      DGGE and/or pyrosequencing was increased by inulin in all three gut locations and
      by the synbiotic in the caecum and colon. In contrast, the probiotic did only
      affect the microbiota diversity in the ileum. Shifts in the DGGE microbiota
      profiles of the caecum and colon were detected for the pro- and synbiotic fed
      animals, whereas inulin profiles were more similar to the ones of the control.
      16S rRNA gene pyrosequencing revealed that all three additives could reduce
      Escherichia species in each gut location, indicating a potential beneficial
      effect on the gut microbiota. An increase of relative abundance of Clostridiaceae
      in the large intestine was found in the inulin group and of Enterococcaceae in
      the ileum of probiotic fed pigs. Furthermore, real-time PCR results showed that
      the probiotic and synbiotic increased bifidobacterial numbers in the ileum, which
      was supported by sequencing results. The probiotic and inulin, to different
      extents, changed the diversity, relative abundance of phylotypes, and community
      profiles of the porcine microbiota. However, alterations of the bacterial
      community were not uniformly between gut locations, demonstrating that
      functionality of feed additives is site specific. Therefore, gut sampling from
      various locations is crucial when investigations aim to identify the composition
      of a healthy gut microbiota after its manipulation through feed additives. 

PMID- 25380796
TI  - Bifidobacterium infantis has a beneficial effect on 5-fluorouracil-induced
      intestinal mucositis in rats.
AB  - Intestinal mucositis is a common toxic side effect in cancer patients receiving
      high-dose chemotherapy. This study aimed to evaluate the beneficial effects of
      Bifidobacterium infantis in a rat model of intestinal mucositis induced by 5
      fluorouracil (5-FU). Thirty male Sprague-Dawley rats were divided into three
      groups: control, 5-FU, and 5-FU + B. infantis. A single intraperitoneal injection
      of 5-FU (150 mg/kg) was used to induce intestinal mucositis. B. infantis (1*109
      cfu) was administered for 11 days, starting from 7 days before 5-FU injection.
      Intestinal mucositis was evaluated based on body weight, villus height,
      immunohistological expression of proliferating cell nuclear antigen (PCNA) and
      nuclear factor kappa beta (NF-kappaB), levels of the pro-inflammatory factors
      interleukin 1 beta and tumour necrosis factor alpha, and myeloperoxidase (MPO)
      concentration. The results showed that the 5-FU + B. infantis group demonstrated
      a higher body weight and villus height, increased expression of PCNA, reduced
      expression of NF-kappaB and pro-inflammatory factors, and lower MPO concentration
      compared to the 5-FU group. These data suggest that probiotic B. infantis is
      effective in reducing chemotherapy-induced intestinal mucositis in rats. 

PMID- 25380798
TI  - Impact of different cryoprotectants on the survival of freeze-dried Lactobacillus
      rhamnosus and Lactobacillus casei/paracasei during long-term storage.
AB  - The production of long shelf-life highly concentrated dried probiotic/starter
      cultures is of paramount importance for the food industry. The aim of the present
      study was to evaluate the protective effect of glucose, lactose, trehalose, and
      skim milk applied alone or combined upon the survival of potentially probiotic
      Lactobacillus rhamnosus CTC1679, Lactobacillus casei/paracasei CTC1677 and L.
      casei/paracasei CTC1678 during freeze-drying and after 39 weeks of storage at 4
      and 22  degrees C. Immediately after freeze-drying, the percentage of survivors
      was very high (>= 94%) and only slight differences were observed among strains
      and cryoprotectants. In contrast, during storage, survival in the dried state
      depended on the cryoprotectant, temperature and strain. For all the protectants
      assayed, the stability of the cultures was remarkably higher when stored under
      refrigeration (4  degrees C). Under these conditions, skim milk alone or
      supplemented with trehalose or lactose showed the best performance (reductions <=
      0.9 log units after 39 weeks of storage). The lowest survival was observed during
      non-refrigerated storage and with glucose and glucose plus milk; no viable cells
      left at the end of the storage period. Thus, freeze-drying in the presence of
      appropriate cryoprotectants allows the production of long shelf-life highly
      concentrated dried cultures ready for incorporation in high numbers into food
      products as starter/potential probiotic cultures.

PMID- 25380799
TI  - Effects of lactic acid bacteria on low-density lipoprotein susceptibility to
      oxidation and aortic fatty lesion formation in hyperlipidemic hamsters.
AB  - We investigated the effects of Streptococcus thermophilus YIT 2001, a strain of
      lactic acid bacteria, on the susceptibility of low-density lipoprotein (LDL) to
      oxidation and the formation of aortic fatty lesions in hyperlipidemic hamsters.
      S. thermophilus YIT 2001 had the highest in vitro antioxidative activity against
      LDL oxidation among the 79 strains of lactic acid bacteria and bifidobacteria
      tested, which was about twice that of S. thermophilus YIT 2084. The lag time of
      LDL oxidation in the YIT 2001 feeding group was significantly longer than in
      controls, but was unchanged in the YIT 2084 group. After the feeding of YIT 2001,
      lag times were prolonged and areas of aortic fatty lesions were dose-dependently
      attenuated, although there were no effects on plasma lipid levels. These results
      suggest that YIT 2001 has the potential to prevent the formation of aortic fatty
      lesions by inhibiting LDL oxidation. 

PMID- 25380800
TI  - Inhibitory activity in vitro of probiotic lactobacilli against oral Candida under
      different fermentation conditions.
AB  - Clinical studies have shown that probiotics positively affect oral health by
      decreasing gum bleeding and/or reducing salivary counts of certain oral
      pathogens. Our aim was to investigate the inhibitory effect of six probiotic
      lactobacilli against opportunistic oral Candida species. Sugar utilisation by
      both lactobacilli and Candida was also assessed. Agar overlay assay was utilised
      to study growth inhibition of Candida albicans, Candida glabrata and Candida
      krusei by Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Lactobacillus
      reuteri SD2112, Lactobacillus brevis CD2, Lactobacillus bulgaricus LB86 and L.
      bulgaricus LB Lact. The inhibitory effect was measured at pH 5.5, 6.4, and 7.2,
      respectively, and in the presence of five different carbohydrates in growth
      medium (glucose, fructose, lactose, sucrose, and sorbitol). Growth and final pH
      values were measured at two-hour time points to 24 h. L. rhamnosus GG showed the
      strongest inhibitory activity in fructose and glucose medium against C. albicans,
      followed by L. casei Shirota, L. reuteri SD2112 and L. brevis CD2. None of the
      lactobacilli tested affected the growth of C. krusei. Only L. rhamnosus GG
      produced slight inhibitory effect on C. glabrata. The lower pH values led to
      larger inhibition zones. Sugar fermentation profiles varied between the strains.
      L. casei Shirota grew in the presence of all sugars tested, whereas L. brevis CD2
      could utilise only glucose and fructose. All Candida species metabolised the
      available sugars but the most rapid growth was observed with C. glabrata. The
      results suggest that commercially available probiotics differ in their inhibitory
      activity and carbohydrate utilisation; the above properties are modified by
      different pH values and sugars with more pronounced inhibition at lower pH. 

PMID- 25380801
TI  - Effect of fermented milk containing Lactobacillus casei strain Shirota on
      constipation-related symptoms and haemorrhoids in women during puerperium.
AB  - Constipation and haemorrhoids are common complaints after childbirth. The
      objective of this pilot study was to evaluate impact of fermented milk containing
      Lactobacillus casei strain Shirota (LcS) on stool consistency and frequency,
      constipation-related symptoms and quality of life, and incidence of haemorrhoids
      in women during puerperium. Forty women who had natural childbirth were
      randomised to group consuming either one bottle/day of fermented milk containing
      at least 6.5*109 cfu of LcS, or placebo, for 6 weeks after childbirth. Subjects
      filled in a diary on their bowel habits including number of bowel movement, stool
      consistency and incidence of haemorrhoids, and answered questionnaires on
      constipation-related symptoms (PAC-SYM) and quality of life (PAC-QOL) during the
      study period. The probiotic group showed the better scores on overall PAC-SYM
      (P=0.013), PAC-SYM subscales of abdominal symptoms (P=0.043) and rectal symptoms
      (P=0.031), and PAC-QOL satisfaction subscale (P=0.037) in comparison with the
      placebo group. In the probiotic group, two to four subjects experienced
      haemorrhoids during the first 3 weeks of treatment. The number decreased in week
      4 and no one had haemorrhoids on most days in week 5-6. In the placebo group, on
      average four subjects had haemorrhoids from the beginning, and no obvious change
      was observed until week 6. No statistically significant effect was observed on
      stool consistency and frequency. The study products did not cause any adverse
      event in the subjects. Results of this study indicate that continuous consumption
      of fermented milk containing LcS might alleviate constipation-related symptoms,
      provide satisfactory bowel habit and result in earlier recovery from haemorrhoids
      in women during puerperium. Nonetheless, there are several limitations in
      interpretation of the results attributed to the study design, including lack of
      baseline data. Further study is required in order to confirm the efficacy. 

PMID- 25380802
TI  - Acid resistance and response to pH-induced stress in two Lactobacillus plantarum
      strains with probiotic potential.
AB  - Two new Lactobacillus plantarum strains, KR6-DSM 28780 and M5 isolated from sour
      turnip and traditional dried fresh cheese, respectively, were evaluated for
      species identity, antibiotic susceptibility, resistance to gastrointestinal
      conditions and adaptive response to low pH. Resistance mechanisms involved in the
      adaptation to acid-induced stress in these two strains were investigated by
      quantitative PCR of the atpA, cfa1, mleS and hisD genes. In addition to absence
      of antibiotic resistance, the two L. plantarum strains showed excellent survival
      rates at pH values as low as 2.4. Adaptive response to low pH was clearly
      observed in both strains; strain KR6 was superior to M5, as demonstrated by its
      ability to survive during 3 h incubation at pH 2.0 upon adaptation to moderately
      acidic conditions. In contrast, acid adaptation did not significantly affect the
      survival rate during simulated passage through the gastrointestinal tract. In
      both strains, induction of histidine biosynthesis (hisD) was upregulated during
      the acid adaptation response. In addition, significant upregulation of the cfa1
      gene, involved in modulation of membrane fatty acid composition, was observed
      during the adaptation phase in strain KR6 but not in strain M5. Cells adapted to
      moderately acidic conditions also showed a significantly increased viability
      after the lyophilisation procedure, a cross-protection phenomenon providing
      additional advantage in probiotic application.

PMID- 25380803
TI  - Clinical compliance of donepezil in treating Alzheimer's disease in taiwan.
AB  - BACKGROUND/RATIONALE: Adherence to cholinesterase inhibitor (ChEI) is associated
      with treatment effectiveness in the treatment of Alzheimer's disease (AD). We
      investigated the clinical adherence to donepezil in Taiwan. METHODS: This was a
      retrospective study. Patients treated with donepezil were recruited from
      Kaohsiung Medical University Hospital and Kaohsiung Municipal Ta-Tung Hospital
      from February 2004 to April 2013. We analyzed their treatment duration in months.
      RESULTS: A total of 273 patients were included in our analysis. Sixty-seven
      patients withdrew from donepezil treatment with mean treatment duration of 28.0
      +/- 25.9 months. Better initial scores on the Mini-Mental Status Examination (P =
      .007), Cognitive Abilities Screening Instrument (P = .003), and the Clinical
      Dementia Rating Scale (CDR) Sum of Boxes (P = .011) were positively associated
      with clinical adherence. The clinical adherent rate was higher in the CDR-0.5
      group than in the CDR-2.0 group with significant difference. CONCLUSION: Although
      there are some limitations in our study, these findings indicate that early
      intervention with ChEI in patients with AD should be emphasized and may lead to a
      better clinical adherence.

PMID- 25380804
TI  - The hypothalamus in Alzheimer's disease: a Golgi and electron microscope study.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder,
      characterized by irreversible decline of mental faculties, emotional and
      behavioral changes, loss of motor skills, and dysfunction of autonomic nervous
      system and disruption of circadian rhythms (CRs). We attempted to describe the
      morphological findings of the hypothalamus in early cases of AD, focusing our
      study mostly on the suprachiasmatic nucleus (SCN), the supraoptic nucleus (SON),
      and the paraventricular nucleus (PVN). Samples were processed for electron
      microscopy and silver impregnation techniques. The hypothalamic nuclei
      demonstrated a substantial decrease in the neuronal population, which was
      particularly prominent in the SCN. Marked abbreviation of dendritic arborization,
      in association with spinal pathology, was also seen. The SON and PVN demonstrated
      a substantial number of dystrophic axons and abnormal spines. Alzheimer's
      pathology, such as deposits of amyloid-beta peptide and neurofibrillary
      degeneration, was minimal. Electron microscopy revealed mitochondrial alterations
      in the cell body and the dendritic branches. The morphological alterations of the
      hypothalamic nuclei in early cases of AD may be related to the gradual alteration
      of CRs and the instability of autonomic regulation. 

PMID- 25380805
TI  - Transporter-mediated uptake of UDP-glucuronic acid by human liver microsomes:
      assay conditions, kinetics, and inhibition.
AB  - This study characterized the kinetics, variability, and factors that affect UDP
      glucuronic acid (UDP-GlcUA) uptake by human liver microsomes (HLM). Biphasic
      kinetics were observed for UDP-GlcUA uptake by HLM. Uptake affinities (assessed
      as Kd) of the high- and low-affinity components differed by more than an order of
      magnitude (13 +/- 6 vs. 374 +/- 175 uM), but were comparable in terms of the
      maximal rate of uptake, with mean Vmax values differing less than 2.3-fold (56 +/
      26 vs. 131 +/- 35 pmol/min per mg). Variability in total intrinsic transporter
      activity (Uint) for microsomal UDP-GlcUA uptake across 12 livers was less than 4
      fold. Experiments performed to optimize the conditions for microsomal UDP-GlcUA
      uptake demonstrated that both components were trans-stimulated by preloading
      (luminal addition) with an alternate UDP-sugar, and essentially abolished by the
      thiol-alkylating agent N-ethylmaleimide. Furthermore, interaction studies
      undertaken with a panel of drugs, alternate UDP-sugars, and glucuronide
      conjugates, at low (2.5 MUM) and high (1000 MUM) UDP-GlcUA concentrations,
      demonstrated that both components were inhibited to varying extents. Notably, the
      nucleoside analogs zidovudine, stavudine, lamivudine, and acyclovir inhibited
      both the high- and low- affinity components of microsomal UDP-GlcUA uptake by
      >45% at an inhibitor concentration of 100 MUM. Taken together, these data
      demonstrate that human liver microsomal UDP-GlcUA uptake involves multiple
      protein-mediated components, and raises the possibility of impaired in vivo
      glucuronidation activity resulting from inhibition of UDP-GlcUA uptake into the
      endoplasmic reticulum membrane by drugs and other compounds. 

PMID- 25380806
TI  - Assessing steatotic liver function after ischemia-reperfusion injury by in vivo
      multiphoton imaging of fluorescein disposition.
AB  - Ischemia-reperfusion injury, a common complication during liver surgery where
      steatotic livers are more prone to the injury, may become more prevalent in the
      growing obese population. This study characterizes liver morphology toward
      understanding changes in subcellular function in steatotic livers exposed to
      ischemia-reperfusion injury through quantitative description of fluorescein
      distribution obtained by minimally invasive in vivo multiphoton microscopy using
      a physiologic pharmacokinetic model. Rats were fed a high-fat diet for 7 days to
      induce liver steatosis. Partial ischemia was induced after reperfusion for 4
      hours, when fluorescein (10 mg/kg) was injected intravenously. Liver images,
      bile, and blood were collected up to 180 minutes after injection. Ischemia
      reperfusion injury was associated with an increase in alanine transaminase levels
      and apoptosis. In addition, steatosis featured lipid droplets and an increase in
      fluorescein-associated fluorescence observed in hepatocytes via multiphoton
      imaging. Analysis of the hepatic concentration-time profiles has suggested that
      the steatosis-induced increase in fluorescein-associated fluorescence mainly
      arises by inducing hepatic fluorescein metabolism. The combination of ischemia
      reperfusion with steatosis exacerbates these effects further. This was confirmed
      by fluorescence lifetime imaging microscopy showing a decreased average
      fluorescence lifetime of the liver, which is indicative of an increased
      production of the metabolite. Our results show the potential of noninvasive dye
      imaging for improving our understanding of liver disease induced by subcellular
      changes in vivo, providing further quantitative measures of metabolic and biliary
      liver function, and hence extending the qualitative liver function tests now
      available. 

PMID- 25380808
TI  - Characteristics of a self-management support programme applicable in primary
      health care: a qualitative study of users' and health professionals' perceptions.
AB  - BACKGROUND: Development of more self-management support programmes in primary
      health care has been one option used to enhance positive outcomes in chronic
      disease management. At present, research results provide no consensus on what
      would be the best way to develop support programmes into new settings. The aim of
      the present study was therefore to explore users' and health professionals'
      perceptions of what would be the vital elements in a self - management support
      programme applicable in primary health care, how to account for them, and why.
      METHODS: Four qualitative, semi-structured focus group interviews were conducted
      in Central Norway. The informants possessed experience in development, provision,
      or participation in a self-management support programme. Data was analysed by the
      Systematic Text Condensation method. RESULTS: The results showed an overall
      positive expectation to the potential benefits of development of a self
      management support programme in primary health care. Despite somewhat different
      arguments and perspectives, the users and the health professionals had a joint
      agreement on core characteristics; a self-management support programme in primary
      health care should therefore be generic, not disease specific, and delivered in a
      group- based format. A special focus should be on the everyday- life of the
      participants. The most challenging aspect was a present lack of competence and
      experience among health professionals to moderate self-management support
      programmes. CONCLUSIONS: The development and design of a relevant and applicable
      self-management support programme in primary health care should balance the
      interests of the users with the possibilities and constraints within each
      municipality. It would be vital to benefit from the closeness of the patients'
      every-day life situations. The user informants' perception of a self-management
      support programme as a supplement to regular medical treatment represented an
      expanded understanding of the self-management support concept. An exploring
      approach should be applied in the development of the health professionals'
      competence in practice. The effect of a self-management support programme based
      on the core characteristics found in this study needs to be evaluated.

PMID- 25380807
TI  - A novel approach for multi-domain and multi-gene family identification provides
      insights into evolutionary dynamics of disease resistance genes in core eudicot
      plants.
AB  - BACKGROUND: Recent advances in DNA sequencing techniques resulted in more than
      forty sequenced plant genomes representing a diverse set of taxa of agricultural,
      energy, medicinal and ecological importance. However, gene family curation is
      often only inferred from DNA sequence homology and lacks insights into
      evolutionary processes contributing to gene family dynamics. In a comparative
      genomics framework, we integrated multiple lines of evidence provided by gene
      synteny, sequence homology and protein-based Hidden Markov Modelling to extract
      homologous super-clusters composed of multi-domain resistance (R)-proteins of the
      NB-LRR type (for NUCLEOTIDE BINDING/LEUCINE-RICH REPEATS), that are involved in
      plant innate immunity. RESULTS: To assess the diversity of R-proteins within and
      between species, we screened twelve eudicot plant genomes including six major
      crops and found a total of 2,363 NB-LRR genes. Our curated R-proteins set shows a
      50% average for tandem duplicates and a 22% fraction of gene copies retained from
      ancient polyploidy events (ohnologs). We provide evidence for strong positive
      selection and show significant differences in molecular evolution rates (Ka/Ks
      ratio) among tandem- (mean = 1.59), ohnolog (mean = 1.36) and singleton (mean =
      1.22) R-gene duplicates. To foster the process of gene-edited plant breeding, we
      report species-specific presence/absence of all 140 NB-LRR genes present in the
      model plant Arabidopsis and describe four distinct clusters of NB-LRR
      "gatekeeper" loci sharing syntenic orthologs across all analyzed genomes.
      CONCLUSION: By curating a near-complete set of multi-domain R-protein clusters in
      an eudicot-wide scale, our analysis offers significant insight into evolutionary
      dynamics underlying diversification of the plant innate immune system.
      Furthermore, our methods provide a blueprint for future efforts to identify and
      more rapidly clone functional NB-LRR genes from any plant species.

PMID- 25380809
TI  - Clinical signs in young patients with stroke related to FAST: results of the
      sifap1 study.
AB  - OBJECTIVES: The present study aimed to evaluate the frequency of warning signs in
      younger patients with stroke with a special regard to the 'FAST' scheme, a public
      stroke recognition instrument (face, arm, speech, timely). SETTING: Primary
      stroke care in participating centres of a multinational European prospective
      cross-sectional study (Stroke in Young Fabry Patients; sifap1). Forty-seven
      centres from 15 European countries participate in sifap1. PARTICIPANTS: 5023
      acute patients with stroke (aged 18-55 years) patients (96.5% Caucasians) were
      enrolled in the study between April 2007 and January 2010. PRIMARY AND SECONDARY
      OUTCOME MEASURES: sifap1 was originally designed to investigate the relation of
      juvenile stroke and Fabry disease. A secondary aim of sifap1 was to investigate
      stroke patterns in this specific group of patients. The present investigation is
      a secondary analysis addressing stroke presenting symptoms with a special regard
      to signs included in the FAST scheme. RESULTS: 4535 patients with transient
      ischaemic attack (TIA; n=1071), ischaemic stroke (n=3396) or other (n=68) were
      considered in the presented analysis. FAST symptoms could be traced in 76.5% of
      all cases. 35% of those with at least one FAST symptom had all three symptoms. At
      least one FAST symptom could be recognised in 69.1% of 18-24 years-old patients,
      in 74% of those aged 25-34 years, in 75.4% of those aged 35-44 years, and 77.8%
      in 45-55 years-old patients. With increasing stroke severity signs included in
      the FAST scheme were more prevalent (National Institute of Health Stroke Scale,
      NIHSS<5: 69%, NIHSS 6-15: 98.9%, NIHSS>15: 100%). Clustering clinical signs
      according to FAST lower percentages of strokes in the posterior circulation
      (65.2%) and in patients with TIA (62.3%) were identified. CONCLUSIONS: FAST may
      be applied as a useful and rapid tool to identify stroke symptoms in young
      individuals aged 18-55 years. Especially in patients eligible for thrombolysis
      FAST might address the majority of individuals. STUDY REGISTRATION: The study was
      registered in http://www.clinicaltrials.gov (No. NCT00414583).

PMID- 25380810
TI  - Introducing the non-invasive prenatal test for trisomy 21 in Belgium: a cost
      consequences analysis.
AB  - BACKGROUND: The first- and second-trimester screening for trisomy 21 (T21) are
      reimbursed for all pregnant women in Belgium. Using a cut-off risk of 1:300 for
      T21, about 5% of all pregnant women are referred for definitive prenatal
      diagnosis using an invasive test, at a sensitivity of (only) 72.5%. The
      sensitivity and specificity of the non-invasive prenatal test (NIPT) are over 99%
      but come at a cost of ?460 (L373) per test. The objective is to estimate the
      consequences of introducing NIPT for the detection of T21. METHODS: A cost
      consequences analysis was performed presenting the impact on benefits, harms and
      costs. Context-specific real-world information was available to set up a model
      reflecting the current screening situation in Belgium. This model was used to
      construct the second and first line NIPT screening scenarios applying information
      from the literature on NIPT's test accuracy. RESULTS: Introducing NIPT in the
      first or second line reduces harm by decreasing the number of procedure-related
      miscarriages after invasive testing. In contrast with NIPT in the second line,
      offering NIPT in the first line additionally will miss fewer cases of T21 due to
      less false-negative test results. The introduction of NIPT in the second line
      results in cost savings, which is not true for NIPT at the current price in the
      first line. If NIPT is offered to all pregnant women, the price should be lowered
      to about ?150 to keep the screening cost per T21 diagnosis constant. CONCLUSIONS:
      In Belgium, the introduction and reimbursement of NIPT as a second line triage
      test significantly reduces procedure-related miscarriages without increasing the
      short-term screening costs. Offering and reimbursing NIPT in the first line to
      all pregnant women is preferred in the long term, as it would, in addition, miss
      fewer cases of T21. However, taking into account the government's limited
      resources for universal reimbursement, the price of NIPT should first be lowered
      substantially before this can be realised.

PMID- 25380811
TI  - One lithium level >1.0 mmol/L causes an acute decline in eGFR: findings from a
      retrospective analysis of a monitoring database.
AB  - OBJECTIVES: Lithium is a mainstay of bipolar disorder treatment, however, there
      are still differences in opinion on the effects of lithium use on renal function.
      The aim of this analysis was to determine if there is an association between
      short-term exposure to various elevated lithium levels and estimated-glomerular
      filtration rate (eGFR) at <=3 months, 6 months (+/-3 months) and 1 year (+/-3
      months) follow-up. SETTING: Norfolk-wide (UK) lithium register and database.
      PARTICIPANTS: 699 patients from the Norfolk database. PRIMARY OUTCOME MEASURES:
      eGFR change from baseline at <=3 months, 6 months (+/-3 months) and 1 year (+/-3
      months) after exposure to a lithium level within these ranges: 0.81-1.0 mmol/L
      (group 2), 1.01-1.2 mmol/L (group 3) and 1.21-2.0 mmol/L (group 4). The reference
      group was patients whose lithium levels never exceeded 0.8 mmol/L. RESULTS:
      Compared to the reference group, groups 3 and 4 showed a significant decrease in
      eGFR in the first 3 months after exposure (p=0.047 and p=0.040). At 6 months (+/
      3 months) postexposure group 4 still showed a decline in eGFR, however, this
      result was not significant (p=0.298). CONCLUSIONS: These results show for the
      first time that a single incident of a lithium level >1.0 mmol/L is associated
      with a significant decrease in eGFR in the following 3 months when compared to
      patients whose lithium levels never exceeded 0.8 mmol/L. It is still not known
      whether the kidneys can recover this lost function and the impact that more than
      a single exposure to a level within these ranges can have on renal function.
      These results suggest that lithium level monitoring should be undertaken at least
      every 3 months, in line with current UK guidelines and not be reduced further
      until the impact of more than one exposure to these lithium levels has been fully
      established.

PMID- 25380812
TI  - Bee venom acupuncture for rheumatoid arthritis: a systematic review of randomised
      clinical trials.
AB  - OBJECTIVE: To assess the clinical evidence for bee venom acupuncture (BVA) for
      rheumatoid arthritis (RA). DESIGN: Systematic review of randomised controlled
      trials (RCTs). SETTING: We searched 14 databases up to March 2014 without a
      language restriction. PARTICIPANTS: Patients with RA. INTERVENTION: BVA involved
      injecting purified, diluted BV into acupoints. We included trials on BVA used
      alone or in combination with a conventional therapy versus the conventional
      therapy alone. PRIMARY OUTCOMES: Morning stiffness, pain and joint swelling
      SECONDARY OUTCOMES: Erythrocyte sedimentation rate (ESR), C reactive protein
      (CRP), rheumatoid factor, the number of joints affected by RA and adverse effects
      likely related to RA. RESULTS: A total of 304 potentially relevant studies were
      identified; only one RCT met our inclusion criteria. Compared with placebo, BVA
      may more effectively improve joint pain, swollen joint counts, tender joint
      counts, ESR and CRP but was not shown to improve morning stiffness. CONCLUSIONS:
      There is low-quality evidence, based on one trial, that BVA can significantly
      reduce pain, morning stiffness, tender joint counts, swollen joint counts and
      improve the quality of life of patients with RA compared with placebo (normal
      saline injection) control. However, the number of trials, their quality and the
      total sample size were too low to draw firm conclusions. TRIAL REGISTRATION
      NUMBER: PROSPERO 2013: CRD42013005853.

PMID- 25380813
TI  - Increased coagulation and suppressed generation of activated protein C in aged
      mice during intra-abdominal sepsis.
AB  - Sepsis is a life-threatening clinical condition that is particularly serious
      among the elderly who experience considerably higher mortality rates compared
      with younger patients. Using a sterile endotoxemia model, we previously reported
      age-dependent mortality in conjunction with enhanced coagulation and insufficient
      levels of anti-coagulant factor activated protein C (aPC). The purpose of the
      present study was to further investigate the mechanisms for age-dependent
      coagulation and aPC insufficiency during experimental sepsis. Intra-abdominal
      sepsis was induced by cecal ligation and puncture (CLP) using 21 or 16 gauge (G)
      needles (double-puncture) on young (4 to 6 mo old) and aged (20 to 25 mo old)
      male C57BL/6 mice. When compared with young mice, aged mice showed significantly
      increased mortality (92% vs. 28%), systemic inflammation, and coagulation in the
      lung and kidney after 21G CLP. Young mice with more severe CLP (16G) showed a
      mortality rate and inflammation equivalent to aged mice with 21G CLP; however,
      enhanced coagulation and kidney dysfunction were significant only in the aged. In
      young mice, increased levels of aPC after CLP were coupled with reduced levels of
      protein C (PC), suggesting the conversion of PC to aPC; however, PC and aPC
      levels remained unchanged in aged mice, indicating a lack of PC to aPC
      conversion. Activation of fibrinolysis, determined by plasma d-dimer levels, was
      similar regardless of age or CLP severity, and plasminogen activator inhibitor-1,
      an inhibitor of fibrinolysis, showed severity-dependent induction independent of
      age. These results suggest that enhanced coagulation in aged mice during sepsis
      is due to dysfunction of the PC activation mechanism. 

PMID- 25380815
TI  - SnoN as a novel negative regulator of TGF-beta/Smad signaling: a target for
      tailoring organ fibrosis.
AB  - Remodeling of the extracellular matrix is beneficial during the acute wound
      healing stage following tissue injury. In the short term, resident fibroblasts
      and myofibroblasts regulate the matrix remodeling process through production of
      matricellular protein components that provide structural support to the damaged
      tissue. This process is largely governed by the transforming growth factor-beta1
      (TGF-beta1) pathway, a critical mediator of the remodeling process. In the long
      term, chronic activation of the TGF-beta1 pathway promotes excessive synthesis
      and deposition of matrix proteins, including fibrillar collagens, which
      ultimately leads to organ failure. SnoN (and its alternatively-spliced isoforms
      SnoN2, SnoA, and SnoI) is one of four members of a family of negative regulators
      of TGF-beta1 signaling that includes Ski and functional Smad-suppressing elements
      on chromosomes 15 and 18. SnoN has been shown to be structurally and functionally
      similar to Ski and has been demonstrated to directly interact with Ski to
      abrogate gene expression. Despite this, little progress has been made in
      delineating a specific role for SnoN in the regulation of myofibroblast phenotype
      and function. This review outlines the current body of knowledge of what we refer
      to as the "Ski-Sno superfamily," with a focus on the structural and functional
      importance of SnoN in mediating the fibrotic response by myofibroblasts following
      tissue injury. 

PMID- 25380814
TI  - Downregulation of adenine nucleotide translocator 1 exacerbates tumor necrosis
      factor-alpha-mediated cardiac inflammatory responses.
AB  - Inflammation contributes significantly to cardiac dysfunction. Although the
      initial phase of inflammation is essential for repair and healing, excessive
      proinflammatory cytokines are detrimental to the heart. We found that adenine
      nucleotide translocator isoform-1 (ANT1) protein levels were significantly
      decreased in the inflamed heart of C57BL/6 mice following cecal ligation and
      puncture. To understand the molecular mechanisms involved, we performed small
      interfering RNA-mediated knockdown of ANT1 and studied tumor necrosis factor
      alpha (TNFalpha)-induced inflammatory responses in myocardium-derived H9c2 cells
      and cardiomyocytes. ANT1 knockdown significantly increased swollen mitochondria
      and mitochondrial reactive oxygen species, concomitant with increased TNFalpha
      induced NF-kappaB reporter gene activity and interleukin-6 and TNFalpha
      expression. A mitochondrial-targeted antioxidant mito-TEMPO attenuated TNFalpha
      induced mitochondrial reactive oxygen species, NF-kappaB reporter gene activity,
      and cytokine expression in ANT1 knockdown cells. Interestingly, TNFalpha or
      lipopolysaccharide (LPS) treatment significantly decreased ANT1 protein levels,
      suggesting a feed-forward regulation of proinflammatory cytokine expression
      activated by ANT1 downregulation. These data suggest that ANT1 downregulation
      contributes to cardiac inflammation post-cecal ligation and puncture. Preventing
      ANT1 downregulation could provide a novel molecular target to temper cardiac
      inflammation. 

PMID- 25380816
TI  - Akt/eNOS signaling pathway mediates inhibition of endothelial progenitor cells by
      palmitate-induced ceramide.
AB  - Palmitate (PA) impairs endothelial progenitor cells (EPCs). However, the
      molecular mechanism underlying the suppressive function of PA remains largely
      unknown. Ceramide, a free fatty acid metabolite, mediates multiple cellular
      signals. We hypothesized that ceramide acts as an intermediate molecule to
      mediate inhibition of EPCs by PA. We first demonstrated that PA could inhibit the
      attachment, migration, and tube formation of EPCs through suppression of the
      Akt/endothelial nitric oxide (NO) synthase (eNOS) signaling pathway. In addition,
      we observed that PA could induce ceramide accumulation in EPCs. To test whether
      the accumulation of ceramide causes EPC dysfunction, the ceramide synthesis
      inhibitors myriocin and fumonisin B1 were used. We that found both inhibitors
      could effectively abolish PA-mediated EPC inhibition. Furthermore, the ceramide
      deacylation inhibitor N-oleoylethanolamine could augment the inhibitory effect of
      PA on EPCs, indicating that it is ceramide, not its metabolites, that mediates
      the suppression of EPCs by PA. We have previously shown that Akt/eNOS
      phosphorylation was reduced after PA treatment, which, in turn, hampered the
      normal bioavailability of NO, leading to impaired functions of EPCs. To test the
      role for ceramide in this process, a clinically used NO donor, sodium
      nitroprusside, was used. We found that sodium nitroprusside could rescue the
      suppressive effects of ceramide on EPCs, suggesting that ceramide-mediated EPC
      inhibition might be through reduction of NO production. Taken together, our
      findings indicated that ceramide-induced reduction of NO might be the molecular
      mechanism for PA-mediated EPC inhibition; thus, targeting either ceramide or NO
      production might be an effective means for improvement of EPC functions in
      diseases. 

PMID- 25380817
TI  - Distribution volumes of macromolecules in human ovarian and endometrial cancers-
      effects of extracellular matrix structure.
AB  - Elements of the extracellular matrix (ECM), notably collagen and
      glucosaminoglycans, will restrict part of the space available for soluble
      macromolecules simply because the molecules cannot occupy the same space. This
      phenomenon may influence macromolecular drug uptake. To study the influence of
      steric and charge effects of the ECM on the distribution volumes of
      macromolecules in human healthy and malignant gynecologic tissues we used as
      probes 15 abundant plasma proteins quantified by high-resolution mass
      spectrometry. The available distribution volume (VA) of albumin was increased in
      ovarian carcinoma compared with healthy ovarian tissue. Furthermore, VA of plasma
      proteins between 40 and 190 kDa decreased with size for endometrial carcinoma and
      healthy ovarian tissue, but was independent of molecular weight for the ovarian
      carcinomas. An effect of charge on distribution volume was only found in healthy
      ovaries, which had lower hydration and high collagen content, indicating that a
      condensed interstitium increases the influence of negative charges. A number of
      earlier suggested biomarker candidates were detected in increased amounts in
      malignant tissue, e.g., stathmin and spindlin-1, showing that interstitial fluid,
      even when unfractionated, can be a valuable source for tissue-specific proteins.
      We demonstrate that the distribution of abundant plasma proteins in the
      interstitium can be elucidated by mass spectrometry methods and depends markedly
      on hydration and ECM structure. Our data can be used in modeling of drug uptake,
      and give indications on ECM components to be targeted to increase the uptake of
      macromolecular substances. 

PMID- 25380818
TI  - Restoration of thyroid hormone balance: a game changer in the treatment of heart
      failure?
AB  - The link between low thyroid hormone (TH) function and heart failure is reviewed
      in the present report. The idea that TH dysfunction may contribute to diseases
      leading to HF has been discussed for over 60 yr. A growing body of evidence from
      animal and human studies, particularly in recent years, suggests that TH
      treatment may improve clinical outcomes. Indeed, if a similar amount of positive
      information were available for a newly developed heart drug, there is little
      doubt that large-scale clinical trials would be underway with considerable
      excitement. THs offer the promise of improving ventricular contraction and
      relaxation, improving coronary blood flow, and inhibiting atherosclerosis, and
      new results suggest they may even reduce the incidence of arrhythmias in heart
      diseases. Are the potential clinical benefits worth the risk of possible
      overdosing? After so many years, why has this question not been answered?
      Clearly, the concept has not been disproven. This review explores the body of
      clinical evidence related to TH dysfunction and heart failure, discuss insights
      into pathophysiological, cellular, and molecular mechanisms provided by animal
      research, and discuss what is needed to resolve this long-standing issue in
      cardiology and move forward. 

PMID- 25380819
TI  - Reactivation of the inactive X chromosome and post-transcriptional reprogramming
      of Xist in iPSCs.
AB  - Direct reprogramming of somatic cells to pluripotent stem cells entails the
      obliteration of somatic cell memory and the reestablishment of epigenetic events.
      Induced pluripotent stem cells (iPSCs) have been created by reprogramming somatic
      cells through the transduction of reprogramming factors. During cell
      reprogramming, female somatic cells must overcome at least one more barrier than
      male somatic cells in order to enter a pluripotent state, as they must reactivate
      an inactive X chromosome (Xi). In this study, we investigated whether the sex of
      somatic cells affects reprogramming efficiency, differentiation potential and the
      post-transcriptional processing of Xist RNA after reprogramming. There were no
      differences between male and female iPSCs with respect to reprogramming
      efficiency or their differentiation potential in vivo. However, reactivating Xi
      took longer than reactivating pluripotency-related genes. We also found that
      direct reprogramming leads to gender-appropriate post-transcriptional
      reprogramming - like male embryonic stem cells (ESCs), male iPSCs expressed only
      the long Xist isoform, whereas female iPSCs, like female ESCs, expressed both the
      long and short isoforms.

PMID- 25380820
TI  - Negative-feedback regulation of the Wnt pathway by conductin/axin2 involves
      insensitivity to upstream signalling.
AB  - Axin and conductin (also known as axin2) are structurally related inhibitors of
      Wnt/beta-catenin signalling that promote degradation of beta-catenin. Whereas
      axin is constitutively expressed, conductin is a Wnt target gene implicated in
      Wnt negative-feedback regulation. Here, we show that axin and conductin differ in
      their functional interaction with the upstream Wnt pathway component Dvl.
      Conductin shows reduced binding to Dvl2 compared to axin, and degradation of beta
      catenin by conductin is only poorly blocked by Dvl2. We propose that
      insensitivity to Dvl is an important feature of the role of conductin as a
      negative-feedback regulator of Wnt signalling.

PMID- 25380821
TI  - CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse
      meiotic prophase.
AB  - In most organisms, telomeres attach to the nuclear envelope at the onset of
      meiosis to promote the crucial processes of pairing, recombination and synapsis
      during prophase I. This attachment of meiotic telomeres is mediated by the
      specific distribution of several nuclear envelope components that interact with
      the attachment plates of the synaptonemal complex. We have determined by
      immunofluorescence and electron microscopy that the ablation of the kinase CDK2
      alters the nuclear envelope in mouse spermatocytes, and that the proteins SUN1,
      KASH5 (also known as CCDC155) and lamin C2 show an abnormal cap-like distribution
      facing the centrosome. Strikingly, some telomeres are not attached to the nuclear
      envelope but remain at the nuclear interior where they are associated with SUN1
      and with nuclear-envelope-detached vesicles. We also demonstrate that mouse
      testis CDK2 phosphorylates SUN1 in vitro. We propose that during mammalian
      prophase I the kinase CDK2 is a key factor governing the structure of the nuclear
      envelope and the telomere-led chromosome movements essential for homolog pairing.

PMID- 25380822
TI  - The exocyst is required for trypanosome invasion and the repair of mechanical
      plasma membrane wounds.
AB  - The process of host cell invasion by Trypanosoma cruzi shares mechanistic
      elements with plasma membrane injury and repair. Both processes require Ca(2+)
      triggered exocytosis of lysosomes, exocytosis of acid sphingomyelinase and
      formation of ceramide-enriched endocytic compartments. T. cruzi invades at
      peripheral sites, suggesting a need for spatial regulation of membrane traffic.
      Here, we show that Exo70 and Sec8 (also known as EXOC7 and EXOC4, respectively),
      components of the exocyst complex, accumulate in nascent T. cruzi vacuoles and at
      sites of mechanical wounding. Exo70 or Sec8 depletion inhibits T. cruzi invasion
      and Ca(2+)-dependent resealing of mechanical wounds, but does not affect the
      repair of smaller lesions caused by pore-forming toxins. Thus, T. cruzi invasion
      and mechanical lesion repair share a unique requirement for the exocyst,
      consistent with a dependence on targeted membrane delivery. 

PMID- 25380823
TI  - Proteasome dysfunction induces muscle growth defects and protein aggregation.
AB  - The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes
      of protein and organelle clearance. The role of the proteasome pathway in
      mammalian muscle has not been examined in vivo. In this study, we report that the
      muscle-specific deletion of a crucial proteasomal gene, Rpt3 (also known as
      Psmc4), resulted in profound muscle growth defects and a decrease in force
      production in mice. Specifically, developing muscles in conditional Rpt3-knockout
      animals showed dysregulated proteasomal activity. The autophagy pathway was
      upregulated, but the process of autophagosome formation was impaired. A
      microscopic analysis revealed the accumulation of basophilic inclusions and
      disorganization of the sarcomeres in young adult mice. Our results suggest that
      appropriate proteasomal activity is important for muscle growth and for
      maintaining myofiber integrity in collaboration with autophagy pathways. The
      deletion of a component of the proteasome complex contributed to myofiber
      degeneration and weakness in muscle disorders that are characterized by the
      accumulation of abnormal inclusions. 

PMID- 25380824
TI  - DAPK-HSF1 interaction as a positive-feedback mechanism stimulating TNF-induced
      apoptosis in colorectal cancer cells.
AB  - Death-associated protein kinase (DAPK) is a serine-threonine kinase with tumor
      suppressor function. Previously, we demonstrated that tumor necrosis factor (TNF)
      induced DAPK-mediated apoptosis in colorectal cancer. However, the protein
      protein interaction network associated with TNF-DAPK signaling still remains
      unclear. We identified HSF1 as a new DAPK phosphorylation target in response to
      low concentrations of TNF and verified a physical interaction between DAPK and
      HSF1 both in vitro and in vivo. We show that HSF1 binds to the DAPK promoter.
      Transient overexpression of HSF1 protein led to an increase in DAPK mRNA level
      and consequently to an increase in the amount of apoptosis. By contrast,
      treatment with a DAPK-specific inhibitor as well as DAPK knockdown abolished the
      phosphorylation of HSF1 at Ser230 (pHSF1(Ser230)). Furthermore, translational
      studies demonstrated a positive correlation between DAPK and pHSF1(Ser230)
      protein expression in human colorectal carcinoma tissues. Taken together, our
      data define a novel link between DAPK and HSF1 and highlight a positive-feedback
      loop in DAPK regulation under mild inflammatory stress conditions in colorectal
      tumors. For the first time, we show that under TNF the pro-survival HSF1 protein
      can be redirected to a pro-apoptotic program.

PMID- 25380825
TI  - EFR3s are palmitoylated plasma membrane proteins that control responsiveness to G
      protein-coupled receptors.
AB  - The yeast Efr3p protein is a main regulator of the Stt4p phosphatidylinositol 4
      kinase at contact sites between the endoplasmic reticulum and the plasma
      membrane. A mutation in its fly homologue Rbo, leads to diminished light
      responses in the eye attributed to progressively impaired PLC signaling. Here, we
      find that Efr3s plays a role in maintaining responsiveness to the type-I
      angiotensin II (AngII) receptors. siRNA-mediated depletion of EFR3A and EFR3B
      impaired the sustained phase of cytosolic Ca(2+) response to high concentration
      of AngII in HEK293 cells that express wild type but not truncated AGTR1 (AT1a
      receptor), missing the phosphorylation sites. Efr3 depletion had minimal effect
      on the recovery of plasma membrane phosphoinositides during stimulation, and AT1
      receptors still underwent ligand-induced internalization. A higher level of basal
      receptor phosphorylation and a larger response was observed after stimulation.
      Moreover, Gq activation more rapidly desensitized after AngII stimulation in Efr3
      downregulated cells. A similar but less pronounced effect of EFR3 depletion was
      observed on the desensitization of the cAMP response after stimulation with
      isoproterenol. These data suggest that mammalian Efr3s contribute to the control
      of the phosphorylation state and, hence, desensitization of AT1a receptors, and
      could affect responsiveness of G-protein-coupled receptors in higher eukaryotes.

PMID- 25380826
TI  - PHD3-SUMO conjugation represses HIF1 transcriptional activity independently of
      PHD3 catalytic activity.
AB  - By controlling HIFalpha hydroxylation and stability, the prolyl hydroxylase
      domain (PHD)-containing proteins are essential to the maintenance of oxygen
      homeostasis; therefore these enzymes are tightly regulated. Small ubiquitin-like
      modifier (SUMO) is a 10-kDa protein readily conjugated to lysine residues of the
      targeted proteins in a process termed SUMOylation. In this study, we introduce
      SUMO conjugation as a novel regulator of PHD3 (also known as EGLN3). PHD3
      SUMOylation occurs at a cluster of four lysines at the C-terminal end of the
      protein. Furthermore, PHD3 SUMOylation by SUMO2 or SUMO3 contributes to PHD3
      mediated repression of HIF1-dependent transcriptional activity. Interestingly,
      PHD3-SUMO conjugation does not affect PHD3 hydroxylase activity or HIF1alpha
      stability, providing new evidence for a dual role of PHD3 in HIF1 regulation.
      Moreover, we show that hypoxia modulates PHD3-SUMO conjugation and that this
      modification inversely correlates with HIF1 activation. PHD3 SUMOylation
      highlights a new and additional layer of regulation that is likely required to
      fine-tune HIF function.

PMID- 25380827
TI  - ATR suppresses apoptosis after UVB irradiation by controlling both translesion
      synthesis and alternative tolerance pathways.
AB  - Ultraviolet (UV) light can stall replication forks owing to the formation of
      bulky lesions in the DNA. Replication across these blocking lesions occurs
      through translesion DNA synthesis, and cells activate the ATR damage responses to
      UV. However, it remains unclear whether lesion bypass requires the replication
      checkpoint because ATR is not necessary for PCNA ubiquitylation. We observed that
      ATR knockdown by siRNA increased replication stress and promoted early induction
      of apoptosis following UVB irradiation in SV40-immortalized human cells,
      including cells from XP-V and XP-C patients. XP-V cells were further sensitized
      by the silencing, indicating that DNA polymerase eta (Pol eta) remains active
      despite ATR control. However, following UVB irradiation, ATR-depleted cells were
      unable to achieve mitosis, as would be expected after the loss of a DNA
      checkpoint control. Thus, ATR also regulates replication arrest recovery
      following UVB-induced damage, independently of Pol eta, in SV40-immortalized cell
      lines. The ATR-mediated DNA damage response regulates replication and different
      tolerance pathways, and in these cells, ATR depletion induces replication
      catastrophe, which contributes to explain the potential of ATR inhibition to
      protect against UVB-induced carcinogenesis. 

PMID- 25380828
TI  - Right lump kidney with varied vasculature and urinary system revealed by
      multidetector computed tomographic (MDCT) angiography.
AB  - Renal ectopia also known as ectopic kidney is an embryological renal anomaly
      characterised by abnormal anatomical location of one or both of the kidneys. This
      can occur in various forms such as (1) crossed fused renal ectopia, (2) ectopic
      thoracic kidney and (3) pelvic kidneys. The lump kidney is one of the six
      variations of crossed fused ectopic kidney. Throughout life, the patient may
      remain asymptomatic, however, symptomatic patients may present with minor
      traumatic injuries due to the abnormal location or normal kidney pathologies.
      During normal embryological development, there is cephalic migration during which
      the kidneys ascend to their normal retroperitoneal location; therefore, an
      ectopic location is as a result of arrested migration. During this embryological
      development the kidney has multiple aorto-illiac branches, which degenerate when
      the kidney reaches its normal location. Here they develop new renal branches from
      the aorta and during an arrested ascent the ectopic kidney tends to retain some
      of the older aorto-iliac vessels. Hence, the arterial supply and the veineux
      drainage are grossly abnormal, reflecting the metanephric malascent and the
      primitive vascular arrangement. The collecting systems also present with
      important anatomical variations. We present an extremely rare case of right lump
      kidney with six renal arteries, two renal veins and two duplicated pelvicalyceal
      systems. 

PMID- 25380829
TI  - Variant arterial supply to the lesser curvature of the stomach and duodenum from
      double inferior phrenic arteries.
AB  - A rare case of the left accessory inferior phrenic artery (IPA) supplying the
      lesser curvature of the stomach and the right accessory IPA supplying the
      duodenum was observed during interventional radiography. To our knowledge,
      variation arteries supplying the stomach and duodenum have never been reported in
      English literature; herein, we report the first case of variant arterial supply
      to the lesser curvature of the stomach and duodenum from double IPAs. 

PMID- 25380833
TI  - Acupuncture points in the book of Serefeddin Sabuncuoglu, a 15th century Turkish
      physician.
AB  - Serefeddin Sabuncuoglu (1385-1468?), the author of Cerrahiyetu'l-Haniyye
      (Imperial Surgery), was a distinguished Ottoman Turkish surgeon. The first
      illustrated Turkish surgical textbook, Cerrahiyetu'l-Haniyye consisted of three
      chapters (ie, cauterisation treatments, surgical procedures and fractures and
      dislocations). Although the main source of the book was Al-Tasrif (Textbook of
      Surgery) by Albucasis (Abu al-Qasim al-Zahrawi; 936-1013 AD), Sabuncuoglu added
      much new information, his clinical experiences and suggestions. The original
      illustrations and human figures made Cerrahiyetu'l-Haniyye the first illustrated
      medical textbook in Turkish and Islamic medicine literature. Cerrahiyetu'l
      Haniyye was also a valuable source for acupuncturists. Some new sections and
      additions revealed that Sabuncuoglu had knowledge of Chinese medicine. In four
      sections of Cerrahiyetu'l-Haniyye (ie, toothache, haemorrhoids, eczema and
      dermatophytosis) Sabuncuoglu described acupuncture techniques and point
      locations. It is likely that the Chinese medicine content of Cerrahiyetu'l
      Haniyye was derived from Central Asian roots of Anatolian Turkish people. 

PMID- 25380834
TI  - Factors affecting the successful implementation and sustainability of the
      Liverpool Care Pathway for dying patients: a realist evaluation.
AB  - OBJECTIVES: The Liverpool Care Pathway (LCP) for the dying patient was designed
      to improve end-of-life care in generalist healthcare settings. Controversy has
      led to its withdrawal in some jurisdictions. The main objective of this research
      was to identify the influences that facilitated or hindered successful LCP
      implementation. METHOD: An organisational case study using realist evaluation in
      one health and social care trust in Northern Ireland. Two rounds of
      semistructured interviews were conducted with two policymakers and 22
      participants with experience and/or involvement in management of the LCP during
      2011 and 2012. RESULTS: Key resource inputs included facilitation with a view to
      maintaining LCP 'visibility', reducing anxiety among nurses and increasing their
      confidence regarding the delivery of end-of-life care; and nurse and medical
      education designed to increase professional self-efficacy, and reduce misuse and
      misunderstanding of the LCP. Key enabling contexts were consistent senior
      management support; ongoing education and training tailored to the needs of each
      professional group; and an organisational cultural change in the hospital setting
      that encompassed end-of-life care. CONCLUSIONS: There is a need to appreciate the
      organisationally complex nature of intervening to improve end-of-life care.
      Successful implementation of evidence-based interventions for end-of-life care
      requires commitment to planning, training and ongoing review that takes account
      of different perspectives, institutional hierarchies and relationships, and the
      educational needs of professional disciplines. There is a need also to recognise
      that medical consultants require particular support in their role as gatekeepers
      and as a lead communication channel with patients and their relatives.

PMID- 25380836
TI  - Hindfoot deformity and calcaneal tuberosity osteotomies.
AB  - Calcaneal tuberosity osteotomies are commonly used to treat coronal plane
      deformities of the hindfoot. Assessing hindfoot alignment can be difficult and
      there is little evidence to guide the physician when considering the surgical
      treatment of these deformities. The indications for a calcaneal osteotomy are
      unclear in the literature because most of the published studies supporting their
      use are confounded by concurrent procedures such as in adult-acquired flatfoot
      correction or cavovarus reconstruction. For the same reason, the biomechanical
      consequences, long-term effects, and performance in vivo are largely unknown.
      LEVEL OF EVIDENCE: Expert opinion, Level V.

PMID- 25380837
TI  - Comparing fixation used for calcaneal displacement osteotomies: a look at removal
      rates and cost.
AB  - BACKGROUND: The calcaneal displacement osteotomy is a procedure frequently used
      by foot and ankle surgeons for hindfoot angular deformity. Traditional techniques
      use compression screw fixation that can result in prominent hardware. While the
      results of the procedure are generally good, a common concern is the development
      of plantar heel pain related to prominent hardware. The primary purpose of this
      study is to retrospectively compare clinical outcomes of 2 fixation methods for
      the osteotomy. Secondarily a cost analysis will compare implant costs to hardware
      removal costs. METHODS: Records were reviewed for patients who had undergone a
      calcaneal displacement osteotomy fixated with either lag screw or a locked
      lateral compression plate (LLCP). Neuropathy, previous ipsilateral calcaneus
      surgery, heel pad trauma, or incomplete radiographic follow-up were exclusionary.
      RESULTS: Thirty-two patients (19.4%) required hardware removal from the screw
      fixation group compared to 1 (1.6%) of the LLCP group, which is significant (P <
      .05). Time to radiographic healing was not significantly different (P = .87). The
      screw fixation group required more follow-up visits over a longer period of time
      (P < .05). Implant cost was remarkably different with screw fixation costing on
      average $247.12, compared to the LLCP costing $1175.59. Although the LLCP cost
      was significantly higher, cost savings were identified when the cost of removal
      and removal rates were included. CONCLUSION: This study demonstrates that this
      device provides adequate stabilization for healing in equivalent time to screw
      fixation. The LLCP required decreased rates of hardware removal with fewer
      postoperative visits over a shorter period of time. Significant savings were
      demonstrated in the LLCP group despite the higher implant cost. LEVELS OF
      EVIDENCE: Therapeutic, Level III, Retrospective Comparative Study.

PMID- 25380838
TI  - Evaluation of standing stability in individuals with flatfeet.
AB  - OBJECTIVE: Flatfoot is one of the most common foot disorders, which not only
      influences the performance of the foot but also affects the alignments of the
      ankle, knee, and hip joints. The performance of the flat-arched individuals
      differs from that of normal individuals during walking. However, there is not
      enough information in the literature regarding their standing stability.
      Moreover, the influence of use of foot insole on standing stability has not been
      evaluated. Therefore, the aim of this study was to evaluate standing stability in
      individuals with flatfoot with and without insole. METHODS: Two groups of normal
      and flat-arched individuals were recruited into this study. A Kistler force plate
      was used to measure the center of pressure (CoP), which is recognized as a good
      approximation of sway of center of gravity in a horizontal plane. Stability was
      determined by calculating the CoP excursions, path length, and velocity in the
      mediolateral and anteroposterior directions. The difference between stability in
      normal individuals and those with flatfoot was examined using the independent t
      test. The paired t test was used to determine the difference between stability in
      each group with and without insole. Significant P value was set at alpha <=.05.
      RESULTS: There was a significant difference between stability of flat-arched and
      normal individuals based on CoP velocity and total velocity. In addition, there
      was no direct correlation between the severity of flatfoot and instability during
      quiet standing. However, the mean values of CoP total velocity during standing
      with and without insole were significantly different (P < .001). CONCLUSION: This
      study suggests that individuals with flatfoot are more unstable when compared
      with normal individuals during quiet standing. It seems that the foot insole
      improves the alignment of foot structure and reduces the forces applied on the
      ligament, thus, improving standing stability. Therefore, stability assessment in
      patients with flatfoot may be important, and the insole is a useful modality that
      can be used to improve stability in this patient group. LEVELS OF EVIDENCE:
      Therapeutic, Level II: Prospective, comparative trial.

PMID- 25380839
TI  - Anatomical transosseous fixation of the deep and superficial fibers of the
      radioulnar ligaments.
AB  - INTRODUCTION: The triangular fibrocartilage complex is in conjunction with the
      interosseous membrane the most important stabilizer of the distal radioulnar
      joint. Lesions of the triangular fibrocartilage complex may cause instability of
      the distal radioulnar joint with serious consequences. Therefore, the goal is to
      reconstruct and provide stability to prevent further harm. SURGICAL TECHNIQUE:
      Based on the anatomical configuration of the radioulnar ligaments, we present a
      technique which addresses both the deep and the superficial fibers of the
      radioulnar ligaments. This surgical procedure can be performed either openly or
      arthroscopically assisted. Two osseous 2-mm tunnels starting from the ulnar neck
      to the foveal surface are created. A nonabsorbable suture is passed through the
      tunnels and the triangular fibrocartilage using a 20-gauge venipuncture needle in
      order to attach the deep fibers. Then a third osseous tunnel starting from the
      lateral base of the styloid process to the medial aspect is created. The suture
      is passed through this tunnel and through the triangular fibrocartilage and
      around the styloid process palmarily using the same needle as before in order to
      anchor the superficial fibers anatomically. After reducing the ulna head the
      sutures are tightened. CONCLUSION: This technique is quite simple and addresses
      the anatomical configuration of the radioulnar ligaments.

PMID- 25380840
TI  - Cisplatin sensitivity is enhanced in non-small cell lung cancer cells by
      regulating epithelial-mesenchymal transition through inhibition of eukaryotic
      translation initiation factor 5A2.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) has been believed to be
      related with chemotherapy resistance in non-small cell lung cancer (NSCLC).
      Recent studies have suggested eIF5A-2 may function as a proliferation-related
      oncogene in tumorigenic processes. METHODS: We used cell viability assays,
      western blotting, immunofluorescence, transwell-matrigel invasion assay, wound
      healing assay combined with GC7 (a novel eIF5A-2 inhibitor) treatment or siRNA
      interference to investigate the role of eIF5A-2 playing in NSCLC chemotherapy.
      RESULTS: We found low concentrations of GC7 have little effect on NSCLC
      viability, but could enhance cisplatin cytotoxicity in NSCLC cells. GC7 also
      could reverse mesenchymal phenotype in NCI-H1299 and prevented A549 cells
      undergoing EMT after TGF-beta1 inducement. eIF5A-2 knockdown resulted in EMT
      inhibition. CONCLUSION: Our data indicated GC7 enhances cisplatin cytotoxicity
      and prevents the EMT in NSCLC cells by inhibiting eIF5A-2.

PMID- 25380841
TI  - A linear relationship between serum high-sensitive C-reactive protein and
      hemoglobin in hemodialysis patients.
AB  - BACKGROUND: Inflammatory process in hemodialysis patients involves hematopoiesis.
      The aim of the study was to determine the relationship between serum C-reactive
      protein (CRP) as a marker of inflammation with hemoglobin in patients under
      hemodialysis. METHODS: Patients under maintenance hemodialysis for more than 3
      months were studied. Serum high-sensitive CRP (hs-CRP) was measured by
      immunoturbidimetric method and hemoglobin < 11 g/dl was considered as anemia.
      Iron deficiency anemia was confirmed by percent transferrin saturation < 20 %.
      Correlation coefficient, linear regression and odds ratio (OR) were used to
      determine the relationship. RESULTS: A total of 73 patients aged 50 +/- 16.9
      years with median hemodialysis duration of 24 (3-280) months entered the study.
      High serum hs-CRP (> 5 mg/l) was found in 42 (57.5 %) and anemia in 32 (43.8 %)
      patients. High CRP was significantly associated with anemia OR = 20.8 (95 % CI
      5.35-81, p = 0.001). After adjustment for age, dialysis duration, blood indices
      and serum albumin, the odds of anemia in the high CRP group remained at a
      significant level of 16.7 (95 % CI 3.7-75, p = 0.001). Hemoglobin levels
      conversely correlated with serum hs-CRP (r = -0.607, r (2) = 0.36, p = 0.001). In
      linear regression analysis for each 1 mg/l increase in serum hs-CRP, hemoglobin
      value increased by 12.4 % (p = 0.002). Serum iron at cutoff level of 54 ug/dl
      discriminated patients with and without iron deficiency anemia with sensitivity
      of 93.3 %, specificity of 84 % and accuracy of 90 % (AUC +/- SE = 0.901 +/- 0.04
      (95 % CI, 0.805-0.998, p = 0.001). CONCLUSION: These findings indicate that in
      hemodialysis patients, the inflammatory process alters hemoglobin level in
      converse correlation with CRP concentration with a linear relationship pattern.
      Serum iron <54 ug/dl indicates iron deficiency anemia with high accuracy.

PMID- 25380842
TI  - The clinical research of the endoscopic sequential treatment for patients with
      intermediate-advanced esophageal cancer: a randomized clinical trial.
AB  - We tried to find an ideal therapeutic regimen for patients with advanced
      esophageal cancer. Totally 240 patients with advanced esophageal cancer were
      randomly divided into experimental group (endoscopic sequential treatment, 126
      cases) and control group (traditional treatment, 114 cases) with a 2-year follow
      up period. The experimental group was randomly divided into three subgroups:
      group A: local chemotherapeutic drug injection with ordinary metal stent
      implantation; group B: local chemotherapeutic drug injection with iodine-125
      particle implantation; and group C: radiofrequency (RF) therapy with ordinary
      metal stent group. The control group was also randomly divided into three
      subgroups: group D: local chemotherapeutic drug injection group; group E: RF
      therapy group; and group F: common metal stent implantation group. The survival
      rate, survival quality, adverse reactions, and complications were compared among
      these groups. A significant improvement of curative effect was found in the
      experimental group. Group A and B had higher survival rate and survival quality,
      and lower esophagotracheal fistula incidence and metastasis rate, compared with
      group C. There was no significant difference in survival rate between group A and
      group B, while the quality of life was higher in group B than in group A. While
      patients in group B had lower esophagotracheal fistula incidence and metastasis
      rate comparing with group A. Local chemotherapeutic drug injection combined with
      iodine-125 particle stent might be an effective sequential treatment to improve
      the life quality of advanced esophageal cancer patients. 

PMID- 25380843
TI  - Resistive index of prostatic capsular arteries as a predictor of prostate cancer
      in patients undergoing initial prostate biopsy.
AB  - To evaluate the value of resistive index (RI) of prostatic capsular arteries in
      diagnosis and evaluation of prostate cancer (PCa) in Chinese patients undergoing
      initial prostate biopsy. A total of 532 consecutive patients undergoing prostate
      biopsy were enrolled in this study. RI was measured on the largest transverse
      section of prostate for each individual. The predictive value of RI was evaluated
      using multivariate logistic regression and receiver operating characteristic
      (ROC) curve analyses. PCa was identified in 217 (40.79%) patients. RI was 0.69 +/
      0.08 and 0.8 +/- 0.08 for patients without and with PCa (p < 0.01). On logistic
      regression RI was significantly associated with PCa (p < 0.01). Using ROC
      analysis RI outperformed tPSA in prediction of PCa in all patients [area under
      ROC curve (AUC) = 0.83, 0.78, respectively]. With the cutoff value of 0.73, RI
      discriminated PCa from non-PCa patients with 81.9% sensitivity, 75.9% specificity
      and 77.63% diagnostic accuracy. Furthermore, The AUC for RI in the discrimination
      of PCa from non-PCa patients in a subset with PSA of 4 to 10 ng/ml, high grade
      from non-high grade PCa patients and advanced from localized PCa patients was
      0.70, 0.77 and 0.80, higher than other parameters (p < 0.05). RI is proved a
      practicable parameter in identifying patients at risk for PCa and predicting the
      grade and stage of PCa before initial prostate biopsy. The value of RI should be
      further explored in the future.

PMID- 25380844
TI  - Measuring residual estrogen receptor availability during fulvestrant therapy in
      patients with metastatic breast cancer.
AB  - It is unknown whether the current dose of fulvestrant, an estrogen receptor (ER)
      antagonist, is sufficient for maximal ER downregulation in patients with
      metastatic breast cancer. We performed a feasibility study to assess ER
      availability before and during fulvestrant. Sixteen patients with ER-positive
      metastatic breast cancer underwent positron emission tomography/computed
      tomography (PET/CT) at baseline (scan 1), day 28 (scan 2), and day 84 (scan 3) to
      monitor tumor [(18)F]fluoroestradiol (FES) uptake. Incomplete reduction in ER
      availability was predefined as <75% decrease in median tumor FES uptake and a
      residual standardized uptake value (SUVmax) of >=1.5. In total, 131 FES-positive
      lesions were identified (median SUVmax of 2.9; range, 1.7-6.5). The median change
      in patients during fulvestrant treatment was -85% at scan 2, but varied widely (
      99% to +60%). Fulvestrant reduced tumor FES uptake incompletely at scan 2 in 6
      (38%) of the 16 patients, which was associated with early progression.
      SIGNIFICANCE: Serial imaging of tumor estrogen uptake by FES-PET can give insight
      into the dose needed for ER antagonists to completely abolish ER. FES-PET showed
      significant residual ER availability in tumors during fulvestrant therapy in 38%
      of patients, which was associated with early progression.

PMID- 25380845
TI  - In vitro immunological effects of blocking CCR5 on T cells.
AB  - Blockade of CC chemokine receptor 5 (CCR5) by maraviroc may induce immunological
      changes independent of its antiviral effects and may have immunoregulation
      properties. This study was designed to determine the effects of blocking CCR5 on
      human activated T cells in vitro and investigate the potential immunological
      mechanisms. Human CD3+ T cells were purified from peripheral blood mononuclear
      cells and then activated by cytokines. We tested the surface expressions and
      relative messenger RNA (mRNA) levels of CCR2, CCR5, CCR6, CCR7, and CXCR3,
      chemotaxis toward their cognate ligands, internalization of chemokine receptors,
      and production of cytokines. In conclusion, blocking CCR5 by maraviroc not only
      can block CCR5 and CCR2 internalization processes induced by CCL5 and CCL2, but
      also inhibit T cell chemotactic activities toward their cognate ligands,
      respectively. Moreover, blocking CCR5 with maraviroc at high doses tends to
      decrease the production of TNF-alpha and IFN-gamma. In addition, there might be a
      form of cross talk between CCR5 and CCR2, and this may offer a novel
      immunological effect for blockade of CCR5. 

PMID- 25380846
TI  - Predicting Improvement After a Bystander Program for the Prevention of Sexual and
      Dating Violence.
AB  - Although evidence suggests that bystander prevention programs are promising
      interventions for decreasing sexual violence and dating violence on college
      campuses, there have been no studies to date evaluating moderators of bystander
      program effectiveness. The current study evaluates whether different demographic
      characteristics, attitudes, knowledge, and behaviors at pretest predict change
      over a 6-month follow-up for students who participated in a bystander prevention
      program. Participants in the three assessments (pretest, posttest, 6-month follow
      up) included 296 college students who were mandated to attend a bystander program
      during their first year orientation. Analyses showed that with few exceptions,
      the bystander program worked best for students who were most at risk given their
      pretest demographics and levels of attitudes condoning dating violence and sexual
      violence, bystander efficacy, and bystander behaviors. Results are discussed in
      terms of suggestions for future research. 

PMID- 25380848
TI  - Activity of hospital transplant coordinators in Malopolskie Province (Poland).
AB  - BACKGROUND: In Poland as well as in other European countries, the number of
      organs from deceased donors is too small to meet the needs of transplantation
      therapy. METHODS: This situation can be improved by increasing the number of
      hospital transplant coordinators in hospitals with potential of donation. Since
      2010, 200 Polish hospitals have employed coordinators whose role is to recruit
      deceased organ donors, to monitor the potential of donation (quality assurance
      program), and to run the training courses. In Malopolskie Province, there are 26
      hospitals in which organ procurement from brain-dead donors is possible. In 13
      hospitals, donor transplant coordinators have been employed. The objective of
      this study was to evaluate the activity of hospitals in Malopolskie Province in
      the field of donor recruitment before and after employment of coordinators (19
      months before and after). For the purpose of the study, the number of hospitals
      with positive effects and with no effects of coordinator employment was
      calculated, and several donation rates were compared in the period before and
      after employment of the coordinator. We also compared the number of deceased
      organ donors in 13 hospitals employing a coordinator and in 13 hospitals without
      a coordinator. RESULTS: The desired impact of employment of coordinators in
      Malopolskie Province measured by improvement of organ donation rates was observed
      in half of the hospitals (7 of 13; 54%) with a transplant donor coordinator. The
      number of potential organ donors increased by 100% (from 24 to 48), and the
      number of actual organ donors increased by 113% (from 16 to 34). The percentage
      of family objections to organ donation decreased (from 17% to 8%). The best
      result of employing coordinators was observed at university hospitals and
      multidisciplinary hospitals and at hospitals in which the coordinator was a
      physician. The worst effect was recorded at county hospitals. CONCLUSIONS: The
      employment of hospital transplant coordinators in Malopolskie Province has a
      global impact on the increase of the number of actual organ donors in that region
      and improvement of organ donation rates, but it is effective only in half of the
      hospitals with coordinators. It indicates that other measurements should also be
      undertaken to run donation programs.

PMID- 25380849
TI  - Correlations between demographics, knowledge, beliefs, and attitudes regarding
      organ transplantation among academic students in Poland and their potential use
      in designing society-wide educational campaigns.
AB  - BACKGROUND: Family objection precludes 10% of cadaveric donations in Poland.
      Academic students represent a socially influential demographic group. Educational
      campaigns improving their attitudes may increase overall donation rates. The aim
      of this study was to assess correlations between knowledge, beliefs, and
      attitudes regarding organ transplantation and the identification of the most
      critical factors affecting one's donation preferences. METHODS: Eight hundred
      students from 4 public universities in Krakow, Poland, participated in the study;
      participants were diverse in age, sex, hometown population, and academic
      discipline (400 medical, 400 non-medical). This cross-sectional study was
      conducted with the use of a group-administered questionnaire inquiring into
      demographics, general and professional knowledge, beliefs, and attitudes toward
      organ transplantation. RESULTS: Attitudes toward organ donation correlate
      positively with beliefs (rho = 0.36), general knowledge (rho = 0.48), and
      professional knowledge (rho = 0.23) scores. Beliefs were proven to correlate with
      general (rho = 0.21) and professional (rho = 0.26) knowledge as well.
      Misconceptions about the medical criteria allowing cadaveric organ recovery,
      distrust for brain death reliability, fear of "do not resuscitate" approach
      toward Organ Donor Card holders, a strong belief in organ trafficking, and
      unawareness of family members' attitudes are the most important factors
      influencing one's refusal/uncertainty to donate. CONCLUSIONS: Knowledge,
      attitudes, and refusal rates differ, depending on the academic discipline as well
      as other demographics, indicating a need for a specifically targeted approach in
      designing educational campaigns. Sources of knowledge are related to donation
      rates, with pre-academic education evaluated as unfavorable, as opposed to
      healthcare providers and the media.

PMID- 25380850
TI  - Attitudes of members of the Baptist Church toward organ transplantation.
AB  - INTRODUCTION: The Baptist Church in Poland has not presented its official stance
      on organ, tissue, or cell transplantation so far. The aim of the work was to find
      out Baptists' knowledge and opinions concerning organ transplantation. METHODS:
      The respondents were 296 members of the Baptist Church. The research tool used in
      the study was an original survey questionnaire. RESULTS: The vast majority of
      Baptists (72%) would agree to have organs removed from a deceased family member.
      The fact of knowing someone who has had an organ transplanted was a factor
      promoting such a decision. Three fourths of the respondents would agree on
      removal of their organs for transplantation after death, but only 47% have talked
      about that with their families. Of the respondents, 37% think that the transplant
      recipient should have the opportunity to meet the family of the donor. The
      respondents who did not agree to have organs removed from a deceased person most
      often mentioned such reasons as aversion to violating bodily integrity of the
      deceased person (55%), religious beliefs (54%), failure to agree with the death
      of the deceased person (46%), not knowing the deceased person's will (34%), and
      lack of trust in health service (32%). CONCLUSION: Propagation of knowledge of
      transplantation is the only effective method of increasing the number of organ
      transplantations, because many ethical, social, and religious barriers in the
      society result from insufficient education.

PMID- 25380851
TI  - Opinions of town residents on organ transplantation.
AB  - INTRODUCTION: Organ transplantation is connected with many very difficult ethical
      and social issues that evoke a lot of emotion. The aim of this work was to
      determine the knowledge and opinions of the 612 residents of selected towns in
      Podlaskie voivodeship (in northeastern Poland) on organ transplantation. MATERIAL
      AND METHODS: A diagnostic poll with the use of a survey questionnaire was
      implemented in the study. The respondents were divided into 2 groups (towns
      <100,000 and >100,000 residents). RESULTS: Respondents from larger towns were
      more often willing to donate organs of close relatives for transplantation than
      those from small towns (67.1% vs 32.9%; P = .022). Respondents with higher
      education levels accepted organ donation from close relatives after their death
      significantly often than those with no more than a primary education (46.7% vs
      22.2%; P < .001). Of the respondents, 83% would agree to donation after death and
      to donating their own organs (higher with primary education, 90.6% vs 63.5%; P <
      .001). Of respondents from big towns, 61.0% have informed their family of the
      decision for donation after death compared with 38.5% of respondents from small
      towns. Respondents with higher education significantly more often informed their
      family of such decision than persons with primary education (60.9% vs 42.9%; P <
      .007). CONCLUSIONS: More emphasis should be on educating the communities living
      in small towns and people with primary and vocational education, because an
      adequate level of knowledge is a significant factor influencing the readiness to
      give one's organs for transplantation.

PMID- 25380852
TI  - Profiles of all 550 procurements and transplantations of kidneys from living
      donors in Poland, 1967-2012.
AB  - INTRODUCTION: Nationwide live organ donor registry is mandatory to ensure the
      quality and safety of kidney procurement from living donors and for donor
      protection. In Poland, this concept is achieved with the use of an Internet tool
      (www.rejestry.net); donation centers are obligated to collect donors' data
      (demographic characteristics, including pre-, peri-, and post-donation and long
      term follow-up). The registry currently handles data from 2008 but is incomplete
      in the collection of historical procurements. The goal of the research was to
      collect in one database all information regarding cases of kidney procurements
      and transplantations from living donors in Poland starting from the first such
      transplant in 1967. MATERIALS AND METHODS: Data were gathered from several
      existing but incomplete records stored by transplant centers. RESULTS: A total of
      550 kidney procurements and transplantations from living donors were made in the
      years 1967 to 2012. We collected 100% of information on the date and donation
      centers and 100% of information regarding the recipients but only 65% of
      information regarding the donor and 80% regarding donor-recipient relations.
      According to the data, women accounted for 60% of living donors and men for 40%
      of living donors. The mean age of a donor was 45 years, and the mean age of a
      recipient was 28 years. Among related donors, parents constituted the majority
      (59%), siblings accounted for 21%, and spouses accounted for 12%. CONCLUSIONS:
      Although the collected data are incomplete, our research provided the Polish live
      donor registry a solid starting point (eg, all dates, center procurements,
      records of transplantations) to enter remaining data and to build a serviceable
      tool for full assessment of all live-donor kidney donations in the country.

PMID- 25380853
TI  - System of donor hospital transplant coordinators maintained and financed by
      national transplant organization improves donation rates, but it is effective
      only in one half of hospitals.
AB  - INTRODUCTION: In 2010, the system of donor hospital transplant coordinators was
      implemented in 200 hospitals in Poland on the basis of contracts with
      Poltransplant. METHODS: This study evaluated whether the system (nationwide,
      maintained and funded by national organization) is sufficient, improved donation
      after brain death rates, and hospital activities. RESULTS: Donation indicators
      over a 21-month period of coordinators' work were compared with the 21-month
      period before their employment. The number of hospitals with a positive effect
      and with no effect was analyzed overall and in groups of hospitals with specific
      profiles. The implemented system resulted in increasing the number of potential
      donors by 27% (effectively, 24%); increasing utilized organs by 20% and
      multiorgan retrievals from 54% to 56%; decreasing the rate of utilized
      organs/actual donors from 2.65 to 2.57; and increasing family refusals from 8.5%
      to 9.3%. A positive effect was achieved in 102 hospitals (51%). Better results
      were achieved in regions where donation were initially low, namely, 59% in
      university hospitals, 63% in hospitals in large cities, 77% in hospitals with 2
      coordinators, 67% in hospitals for adults, and 52% in hospitals where the
      coordinator was a doctor and not a nurse. This system resulted globally in
      increasing donation rates, but was effective only in one half of hospitals.
      CONCLUSIONS: Additional activities should be introduced to improve these results
      (quality systems, trainings, techniques for monitoring potential of donation,
      changes in profile of a coordinator). A formal analysis of coordinators'
      activities gives also the national organization a rational basis for their
      employment policy, taking into account the characteristics of hospitals and
      coordination teams.

PMID- 25380854
TI  - Influence of empathy, beliefs, attitudes, and demographic variables on
      willingness to donate organs.
AB  - BACKGROUND: As organ transplantation has become a more routine medical procedure,
      there has been a growing interest in studying people's attitudes and knowledge
      concerning organ donation. Trait empathy and self-interest influence different
      pro-social behaviors to a great extent; still, their role in the promotion of
      organ donation registration and willingness to donate organs remains unclear.
      However, people with higher levels of empathy report more altruistic beliefs. We
      assessed the influence of empathy, beliefs, and demographic variables on
      willingness to donate organs. METHODS: We included 191 subjects (135 female, 56
      male) aged 16-61 years (mean, 26.86 +/- 12.88), who participated in educational
      meetings concerning organ donation. The group was composed of students, teachers,
      and nurses. Survey tools included the Individual Questionnaire: Study of
      Attitudes Towards Transplantation, consisting of 26 closed-ended questions (with
      the consent of the Krakow Statistical Office) and the Empathy Scale by Mehrabian
      and Epstein. RESULTS: Of the respondents, 97.4% accept transplantation from
      living donors, 95.8% accept deceased donations, and 78.5% agree with posthumous
      life-saving organ donation. The majority of respondents (73%) achieved an average
      level of empathy, and 20.4% of respondents exhibited considerably higher empathy
      levels. There was a significant difference between the respondents' sex and their
      agreement to make a life-saving organ donation. Differences were found among the
      groups, the attitudes and willingness to donate organs, and between the level of
      empathy and agreement/consent for organ donation. CONCLUSIONS: Our findings show
      that the group in general has favorable beliefs about transplantation and
      declares a willingness to make a posthumous organ donation. These beliefs vary
      based on demographic variables. Education about organ and tissue donation a has a
      positive impact on donation and transplantation rates.

PMID- 25380855
TI  - Current state of knowledge, beliefs, and attitudes toward organ transplantation
      among academic students in Poland and the potential means for altering them.
AB  - INTRODUCTION: Students manifest a high level of social commitment. Improving
      their knowledge and developing more positive attitudes toward organ
      transplantation may increase the number of organ donations. This study was an
      assessment of the knowledge and attitudes toward organ transplantation among
      young people in Poland, with an overview of current beliefs and potential methods
      for improving transplantology awareness. SUBJECTS AND METHODS: The study included
      400 medical students and 400 nonmedical students from public universities in
      Krakow, Poland. Data were collected by using an anonymous questionnaire examining
      demographic factors and transplantology issues. RESULTS: Despite the overall
      positive attitude toward transplantology among academic students in Poland, the
      state of knowledge of the nonmedical population remains relatively low. The most
      important issues for social education to focus on are the role of presumed
      consent and brain death diagnosis, actual hazards of living donations, recipient
      qualification criteria, and the attitudes of religious authorities. The overall
      level of knowledge and the number of positive attitudes were significantly higher
      among medical students than among nonmedical students, proving that formal
      educational programs are more efficient than the more accessible but less
      reliable sources of knowledge. CONCLUSIONS: Introduction of transplantology
      issues in schools and churches, promoting the positive outcomes of organ
      transplantation rather than negating false beliefs, and eliminating misleading
      information from the media may significantly increase young people's knowledge
      and result in more positive attitudes toward transplantology in a society-wide
      fashion. This outcome could create a favorable background for introducing an opt
      in system of consent for organ donation.

PMID- 25380856
TI  - Organ Donor Cards--concepts versus reality: a study among academic students in
      Poland.
AB  - INTRODUCTION: Organ Donor Cards (ODCs), despite presenting no legal value in
      Poland, are considered an important mean of expressing one's intent toward organ
      donation. This study was an assessment of the effectiveness of ODCs in social
      communication and their connection to one's transplantology knowledge, attitude,
      and beliefs. SUBJECTS AND METHODS: The study included 400 medical students and
      400 nonmedical students from public universities in Krakow, Poland. Data were
      collected by using an anonymous questionnaire with attached ODCs examining
      demographic factors and transplantology issues. RESULTS: Approximately 41% of
      students possess an ODC, and the majority of the remaining group are willing to
      sign one. The main reasons for not having an ODC originate from a positive or
      neutral interest in organ donation (eg, previous conversation with the family,
      lack of knowledge about ODCs and how to obtain them) rather than a negative one
      (fear of "do not resuscitate" approach or organ trade) and remain open for
      modification. Eighty-three percent of ODC holders are aware of its ethical rather
      than legal value, and 3 of 4 have informed their family about their attitude,
      proving ODCs are an effective way of expressing one's intent toward organ
      donation. An actual ODC holder presents a more explicit positive attitude than a
      potential one, and his or her level of transplantology knowledge is significantly
      higher. CONCLUSIONS: The support for informed consent for organ donation is
      particularly strong among students presenting with the highest level of
      transplantology awareness, with a good/very good state of knowledge and extremely
      positive attitudes, already owning an ODC, and using it correctly. Thus, such a
      decision will have the status of a truly conscious and thoroughly considered
      choice.

PMID- 25380857
TI  - Brain death versus irreversible cardiac arrest--the background and consequences
      of young people's opinions on stating death in Polish transplantology.
AB  - BACKGROUND: Brain death and irreversible cardiac arrest (ICA) are legally valid
      diagnoses obligatory for stating organ donors' death in Poland. Their
      misinterpretation may affect one's attitude toward organ donation. We assessed
      young people's knowledge and attitudes toward stating death in transplantology
      and their impact on attitude toward organ transplantation. METHODS: A total of
      400 medical and 400 nonmedical students from public universities in Krakow,
      Poland, participated. Data were collected with a questionnaire examining
      demographic factors and transplantologic issues. RESULTS: Brain death diagnosis
      has a stronger association with stating death in transplantology than ICA,
      although the level of trust for this diagnosis remains relatively low among
      nonmedical respondents (38.5% vs 78.5%). Professional knowledge about stating
      brain death did not correlate with the level of trust for said diagnosis as
      strongly as it was expected, suggesting the presence of alternate contributing
      factors, some identified as doubts about brain death criteria (31.5%), distrust
      for the medical staff's education (25%), and objectivity (20%). CONCLUSIONS: The
      number of nonpositive attitudes toward organ transplantation was significantly
      higher among respondents unwilling to accept brain death as the death of a human
      being, a statement proven to be related to one's opinion about the reliability of
      said diagnosis, one's awareness of an alternative diagnosis of ICA, and one's
      general transplantologic knowledge. However, a low number of respondents
      acknowledging ICA as the only diagnosis valid for stating death of a cadaveric
      donor (7.6%) suggests that the majority of young Poles are willing to accept
      brain death as an equally valid, if not more significant, diagnosis.

PMID- 25380858
TI  - Analysis of the effect of cryoprotectant medium composition to viability of
      autologous hematopoietic cells collected by leukapheresis.
AB  - OBJECTIVES: Cryopreservation of hematopoietic stem cells intended for autologous
      transplantation is a crucial element of the banking process. Although
      cryopreservation techniques are well known, improvement is needed. This study was
      designed to optimize cryopreservation to improve the quantitative and qualitative
      parameters of hematopoietic stem cells in the material intended for
      transplantation. We used available opportunities to provide the best quantitative
      and qualitative parameters of hematopoietic stem cell transplants processed in a
      closed system. MATERIAL AND METHODS: Two hundred forty-eight products of
      hematopoietic stem cells collected by leukapheresis from patients with
      lymphoproliferative disorders create the basis of this report. The material was
      frozen in a controlled-rate freezer and stored in containers in the vapor phase
      of LN2 (-160 degrees C). The composition of a cryoprotectant medium was modified.
      For freezing, 192 probes were used with a cryoprotective medium containing 20%
      dimethyl sulfoxide (DMSO) and enriched RPMI 1640. For 56 samples, we used 20%
      DMSO in autologous plasma harvested during leukapheresis. Products of
      hematopoietic stem cells and cryoprotectant medium were combined in a 1:1 ratio.
      The final number of nuclear cells did not exceed 2 * 10(8)/mL. Analysis was
      performed after thawing the probes. Viability of nuclear cells has been assessed
      using the microscopic technique after incubation in Trypan blue and the CD34+
      cells by flow cytometry using the 7-aminoactynomycin D. A statistical analysis
      has been conducted using the Statistica program (StatSoft, Cracow, Poland).
      RESULTS AND CONCLUSIONS: The results show that the application of autologous
      plasma is linked with higher viability of nuclear cells and CD34+ cells.
      Moreover, statistical analysis of the nuclear cells and CD34+ cells viability
      differs significantly between groups frozen using RPMI 1640 and autologous plasma
      (P < .05). To assess the viability of CD34+, cells frozen using RPMI 1640 results
      showed a large span of at 16.4% to 99.1% living cells.

PMID- 25380859
TI  - Biolasol: novel perfusion and preservation solution for kidneys.
AB  - INTRODUCTION: Biolasol solution (Pharmaceutical Research and Production Plant
      "Biochefa," Sosnowiec, Poland) is a novel extracellular perfusion and ex vivo
      hypothermic kidney preservation solution. It ensures maintenance of homeostasis,
      reduces tissue edema, has low viscosity, and allows the graft to preserve
      structural and functional integrity. It minimizes ischemia-reperfusion damage.
      METHODS: Perfundates from control and transplanted kidneys flushed with Biolasol
      or ViaSpan solutions (Arkas, Warszawa, Poland) were analyzed. Parameters of serum
      and urine collected from 12 pigs after auto-transplantation were also analyzed.
      Renal medulla was investigated for structural alterations by analyzing
      hematoxylin and eosin-stained slides. The mean survival time of pigs after the
      auto-transplantation procedure was the measure for the novel Biolasol solution
      effectiveness. RESULTS: We observed a statistically significant decrease in
      marker enzyme levels alanine transaminase, aspartate transaminase, lactic
      dehydrogenase, and ions (Na and K) in pigs with grafts flushed with Biolasol.
      Histopathologic examination revealed that the renal cortex structure was not
      damaged after the use of Biolasol solution. CONCLUSION: Biolasol solution
      protects kidneys against ischemia damage and does not differ significantly from
      the "golden standard" ViaSpan solution.

PMID- 25380860
TI  - Comparison of endothelial nitric oxide synthase and endothelin-1 levels in
      kidneys removed from living pigs after cardiac arrest and brain death.
AB  - OBJECTIVES: The aim of this paper was to describe differences between levels of
      endothelial nitric oxide synthase (NOS-3) and endothelin-1 (ET-1) in swine
      kidneys removed from living donors (group I) and after inducing brain death by
      brain herniation (group II) and cardiac arrest (group III). METHODS: Each group
      consisted of 3 animals who underwent dual renal removal procedure; kidneys were
      further rinsed according to standardized procedure with Biolasol perfusion
      liquid, stored for 24 hours (4 degrees C), and rinsed again. Renal specimens of 4
      g mass, including renal cortex and medulla, were collected before and after
      perfusion (times 0 and 1), after 12 hours (time 2), and after reperfusion (time
      3). Enzyme-linked immunosorbent assay was used to describe levels of NOS-3 and ET
      1 in collected tissues homogenates. Mann-Whitney U test was used to compare
      results in groups in relation to total protein content (ng/mg), and the
      correlation between the 2 substances was measured with the use of Spearman rho.
      RESULTS: Group I presented low and stable levels of NOS-3 in all time intervals
      (averages, 0.73, 0.99, 0.52, and 0.89, respectively). Level sof ET-1 were similar
      (0.87, 0.63, 0.69, and 0.86, respectively), and significant correlation between
      levels of the 2 substances was observed. Increased levels of NOS-3 (1.89 and
      1.86) and ET-1 (1.38 and 1.49) were observed directly after removal in groups II
      and III and further maintained during organ storage. No correlation in group I
      was observed, and after perfusion significantly lower level of NOS-3 was observed
      in kidneys removed after brain death in relation to group III (1.77 vs 2.60).
      CONCLUSIONS: The lowest and stable levels of NOS-3 and ET1 during storage were
      observed in kidneys removed from living donors. Levels of analyzed substances in
      this group showed correlation in subsequent time intervals.

PMID- 25380861
TI  - Toll-like receptors 2 and 4 in pigs' kidneys early after autotransplantation
      procedure.
AB  - OBJECTIVES: The aim of this paper was to evaluate mRNA expression of Toll-like
      receptors 2 (TLR2) and 4 (TLR4) and the adaptor protein myeloid differentiation
      primary-response protein 88 (MyD88) in pigs' kidneys 14 and 30 days after
      autotransplantation. METHODS: The research was conducted on 12 animals that
      underwent left renal transplantation procedure with further standardized rinsing
      with Biolasol solution and 24 hours' storage in 4 degrees C; subsequently the
      kidneys were implanted in the right retroperitoneal space after right-side
      nephrectomy. Six randomly chosen animals (group I) were under observation for 14
      days, the other 6 (group II) for 30 days. After these observation periods, the
      animals were killed and 4-g samples were collected from the renal cortex and
      medulla. RESULTS: Expression of mRNA in homogenates of collected samples were
      determined with the use of reverse-transcription polymerase chain reaction
      analysis. Obtained results in both groups, presented in relation to GAPDH, were
      compared with the use of Mann-Whitney U test. Stable graft function was observed
      in all animals from the 2nd day after the procedure. TLR2 in group I reached the
      mean value of 3.64 and was statistically significantly higher than in group II
      (2.19). Inverse proportion was observed in case of mRNA for TLR4: group II
      presented 2 times higher value than group I (0.25 vs 0.11). Similarly,
      significant difference was observed in MyD88 (group I, 0.067; group II, 0.45).
      CONCLUSIONS: At 14 days after autotransplantation of a pig kidney, mRNA
      expression for TLR2 is dominant; later, expression increases for TLR4 and MyD88.

PMID- 25380862
TI  - Cytochrome P450 3 A expression in pigs livers after 24-hour preservation in
      Biolasol solution depending on the type of transgenesis.
AB  - BACKGROUND: An insufficient number of organs for transplantation shows the need
      for the development of new technologies. Xenotransplantation might be the answer.
      OBJECTIVE: To determine if the type of transgenesis influences the level of
      CYP3A4, which takes an active part in xenobiotics metabolism in livers after 24
      hour storage, depending on the kind of solution used for preservation. MATERIALS
      AND METHODS: The experiment was carried out on 30 livers of Polish White Landrace
      divided into 5 groups depending on transgene type. The following human genes were
      transferred: alpha1,2-fucosyltransferase (groups I and II), alpha-galactosidase
      (III), combined alpha1,2-fucosyltransferase/alpha-galactosidase transgene (IV),
      and livers without modification (V). The livers were perfused and subsequently
      stored for 24 hours in Ringer's solution (group I) or Biolasol solution (II-V).
      Reperfusion/reflush was performed. CYP3A29 isomer concentration was analyzed in
      liver specimens collected twice: 30 minutes after perfusion and 30 minutes after
      reperfusion/reflush. Expression of mRNA CYP3A29 was marked using RT-PCR analysis
      and of protein CYP3A29 using Western blotting technique. RESULTS: The most
      significant decrease in protein CYP3A29 expression after 24-hour preservation was
      observed in group I (55.88% decrease), while the least significant was observed
      in group IV (10.44% decrease). mRNA expression evaluation was similar: the most
      significant decrease was observed in group I (87.8% decrease) and the least
      significant in group III (4.6% decrease). CONCLUSION: alpha1,2-Fcosyltransferase
      transgene seems to influence mRNA and protein CYP3A expression in case of liver
      grafting and preservation for transplantation. CYP3A expression was also
      influenced by the kind of preservation solution used.

PMID- 25380863
TI  - Interleukin-6 concentration in the transgenic pig's liver preserved for 24 hours
      in Biolasol solution.
AB  - INTRODUCTION: Increasing the human lifespan contributes to a higher number of
      patients with end-stage organ failure, which in turn stimulates the search for
      alternative sources. Xenotransplantation seems to be a promising approach in this
      respect. OBJECTIVE: Analysis of changes in interleukin (IL)-6 concentration
      during 24-hour preservation of transgenic swine livers, depending on the kind of
      transgenesis and preservation solution used. MATERIALS AND METHODS: The
      experiment was carried out in swine livers with transferred human genes that were
      divided into 5 groups. The following human genes were transferred: alpha1,2
      fucosyltransferase (group I and II), alpha-galactosidase (III), combined alpha1,2
      fucosyltransferase/alpha-galactosidase transgene (IV), and livers without
      modification (V). The livers were perfused and subsequently stored for 24 hours
      in Ringer's (group I) or Biolasol solutions (II-V). Reflush was then performed.
      IL-6 concentration was analyzed in the solution samples collected at the
      beginning and end of perfusion, and after 24 hours of preservation. ELISA was
      used to evaluate IL-6 concentration. RESULTS: In liver homogenates from group I,
      IL-6 concentration after 24 hours of preservation increased by 8.24% compared to
      the levels observed after perfusion, whereas in the other groups IL-6
      concentration decreased. The most significant decrease, 49.51%, was observed in
      group II; the least significant in group IV, 10.72%. In case of supernatants, a
      statistically significant increase of AUC0-30min level in relation to perfusion
      was observed in every group after 24-hour preservation and reperfusion. The
      highest values of AUC0-30min were observed in group I (alpha1,2
      fucosyltransferase, Ringer's solution). CONCLUSION: The study indicates the
      hepatoprotective action of Biolasol solution.

PMID- 25380865
TI  - Splenectomy attenuates the course of kidney ischemia-reperfusion injury in rats.
AB  - INTRODUCTION: Renal ischemia-reperfusion injury (IRI) initiates inflammatory
      response with synthesis of free oxygen radicals, chemokines, and cytokines which
      attract neutrophils and monocytes, which then differentiate into macrophages and
      dendritic cells, activating adaptive immune response. The spleen is the main
      source of both monocytes and lymphocytes. The aim of this study was to assess
      whether splenectomy performed before or upon IRI affects post-ischemic and long
      term renal function. METHODS: Two weeks after right nephrectomy, the left kidney
      pedicle was clamped for 45 minutes in 24 rats. After the clip insertion, the
      spleen was removed in 12 animals and the remaining 12 rats underwent sham
      splenectomy. In the second experiment, splenectomy (n = 9) or sham procedure (n =
      9) was performed simultaneously with right nephrectomy, 2 weeks before left
      kidney ischemia. The excretory function of the kidney was evaluated 48 hours and
      7 days after ischemia. In the experimental model of chronic renal failure, 14
      days before right nephrectomy, the prolonged 90-minute ischemia was induced in 32
      rats with simultaneous splenectomy (n = 16) or sham procedure (n = 16). In long
      term observation, the renal function and mortality rate was evaluated. RESULTS:
      Kidney function preservation was superior in rats that underwent splenectomy
      together with renal ischemia when compared to controls. This was further
      expressed with a 2 times lower mortality rate in splenectomized animals in 6
      months observation after prolonged renal ischemia. Renoprotective effect was not
      observed when splenectomy was performed 2 weeks before IRI. CONCLUSIONS: The
      results suggest a detrimental influence of the spleen on the development of renal
      IRI.

PMID- 25380864
TI  - Nephroprotective effect of pentoxifylline in renal ischemia-reperfusion in rat
      depends on the timing of its administration.
AB  - BACKGROUND: Renal ischemia-reperfusion injury (IRI) induces inflammatory reaction
      damaging kidney. Pentoxifylline (PTX) given before IRI attenuates inflammation
      and prevents ischemic acute kidney injury (iAKI). Given that in clinical settings
      IRI is not always predictable, we aimed to assess whether PTX administration
      during or shortly after IRI affects the course of iAKI in the rat. METHODS: In 58
      male 10-week-old Sprague-Dawley rats, 14 days after right nephrectomy, a 45
      minute clamping of solitary renal pedicle was conducted. PTX 100 mg/kg body
      weight or 0.9% NaCl 1 mL were given subcutaneously either 60 minutes before renal
      ischemia, 1 minute into ischemia, or 60 minutes after clamp release. Creatinine
      clearance (ClCr; mL/min/kg body weight), fractional excretions of sodium (FENa
      [%]) and potassium (FEK [%]), and urine protein/ClCr ratio (Uprot/ClCr [mg/1 mL
      ClCr]) at 48 hours after IRI were compared between PTX-treated animals and
      respective controls (Mann-Whitney U test). RESULTS: Kidney function was improved
      in rats given PTX before IRI compared with controls: ClCr 2.10 +/- 0.44 versus
      1.03 +/- 0.18; FENa 0.16 +/- 0.12 versus 0.84 +/- 0.55; FEK 40.3 +/- 13.0 versus
      75.5 +/- 17.9, respectively (all P < .001). There was no difference in
      proteinuria: Uprot/ClCr 0.004 +/- 0.002 versus 0.004 +/- 0.002. Conversely, the
      analyzed parameters did not differ between animals administered PTX during IRI
      and controls: ClCr 0.42 +/- 0.34 versus 0.73 +/- 0.43; FENa 2.98 +/- 2.71 versus
      3.16 +/- 3.05; FEK 280.1 +/- 155.7 versus 206.2 +/- 154.1; and Uprot/ClCr 0.031
      +/- 0.029 versus 0.029 +/- 0.031, respectively, nor between rats given PTX after
      IRI and controls: ClCr 0.29 +/- 0.38 versus 0.40 +/- 0.47; FENa 4.25 +/- 3.55
      versus 3.80 +/- 3.94; FEK 284.9 +/- 117.5 versus 243.0 +/- 150.6; and Uprot/ClCr
      0.044 +/- 0.018 versus 0.055 +/- 0.061, respectively. CONCLUSIONS: PTX given only
      before, and not at the time of renal ischemia or after reperfusion, alleviates
      subsequent iAKI in the rat. This implicates usefulness of PTX in the clinical
      settings of expected renal ischemia, like kidney transplantation, and suggests
      potential benefits of PTX in peritransplant period foremost with donor
      pretreatment.

PMID- 25380866
TI  - Influence of the hemodynamic status of multiorgan donors on long-term kidney
      graft survival--a multivariable analysis.
AB  - BACKGROUND: The quality of transplanted organ and timing of the initiation of its
      effective function depends on many factors potentially causing graft dysfunction.
      The aim of this study was to evaluate the influence of the cardiovascular status
      of multiorgan donors on the long-term kidney graft survival over a 15-year
      observation period. METHODS: In 2007, the authors of this study published a
      multicenter prospective study evaluating the influence of the hemodynamic status
      of multiorgan donors on the early function of transplanted kidney. The results of
      that study showed that mean arterial pressure, central venous pressure, and
      pulmonary capillary wedge pressure values of the donor importantly influence the
      frequency of delayed graft function after renal transplantation. The present
      analysis covers the effect of the donor's hemodynamic status parameters on graft
      function time within the 15-year observation period. Univariate and multivariate
      analyses using the Cox regression proportional hazard model were performed to
      evaluate the prognostic parameters for overall survival and renal graft survival
      time. P < .05 was considered to be significant. RESULTS: The univariate analysis
      showed a significantly shorter time of graft survival in the group of recipients
      who had a kidney retrieved from donors with lower pulmonary capillary wedge
      pressure values (P = .038) and lower cardiac index values (P = .039). The same
      results were obtained for the multifactorial Cox logistic regression analysis.
      CONCLUSIONS: The filling of the intravascular bed of the donor as determined by
      pulmonary capillary wedge pressure and maintained donor tissue perfusion as
      determined by cardiac index, impose important factors influencing long-term
      kidney graft survival.

PMID- 25380867
TI  - Anti-human leukocyte antigen antibodies are present in blood of blood donors: is
      therapy with blood preparations safe for graft recipients?
AB  - BACKGROUND: Blood products infusions are often administrated to graft recipients.
      Post-transfusion reactions of anti-human leukocyte antigen antibodies (anti-HLA)
      are responsible for transfusion-related acute lung injury, but cases of graft
      rejection after blood product infusions were recently also proven. METHODS: The
      aim of this study was to assess, with the use of the very sensitive Luminex
      technology and traditional lymphocytotoxic test, the prevalence and cytotoxic
      activity of anti-HLA in blood donors with different medical histories to evaluate
      a potential risk of post-transfusion immune complications. Data were analyzed
      according to different normalized background cutoffs (1.5, 2.2; and the high
      cutoffs-10.8 for I class and 6.9 for II class anti-HLA). RESULTS: We observed
      that anti-HLA may be present in 36% of donors, and even in up to 73.6% of risk
      groups. Significant risk factors included female sex (23.9% to 64.2% for
      different cutoffs) and pregnancy history (30% to 72.5%), regardless of the cutoff
      used in analysis, whereas sera from female donors showed lower cytotoxicity
      (panel reactive antibodies). Anti-HLA were also detected in men (3.7% to 37%), in
      donors after a transfusion (0% to 62.5%), and even with no known risk factors
      (3.8% to 26.9%). CONCLUSIONS: Luminex technology is a sensitive tool in anti-HLA
      detection, but consensus in measurement interpretation for blood donors is
      needed. Selection of blood products on the basis of medical history can be a
      useful alternative for routine testing of blood donors. The clinical significance
      of treatment of graft recipients with blood products requires further study;
      until then, more attention should be paid to possible complications.

PMID- 25380868
TI  - Cytomegaloviral infection in solid organ transplant recipients: preliminary
      report of one transplant center experience.
AB  - BACKGROUND: Despite advances in immunosuppressive therapy and post
      transplantation care, antiviral prevention, and therapy, cytomegalovirus (CMV)
      infection remains the most common viral infection after solid organ
      transplantation (SOT). METHODS: This study included 2,375 patients under the care
      of our transplant center during the 1-year period from June 2012 to June 2013.
      There were 351 patients (14.78%) suspected and tested for CMV infection with the
      use of viral DNA amplification test. RESULTS: Symptoms that triggered diagnostics
      were graft dysfunction in 24 (55.8%), diarrhea in 18 (41.9%), fever in 15
      (34.9%), leukopenia in 14 (32.6%), abdominal pain in 13 (30.2%), nausea in 7
      (16.3%), cough in 6 (14%), and shivers in 2 (4.7%). Positive test results were
      obtained in 43 patients (12.3% of patients tested and 1.8% of the entire cohort).
      The group consisted of 17 women (39.5%) and 26 men (60.5%), 26 kidney (60.5%) and
      17 liver (39.5%) transplant recipients, aged 49.3 years (SD 14.9). The initial
      viral load was median 8,093 (range: 4,232-219,180) copies/mL. The mean
      ganciclovir (GCV) treatment duration was 19.05 (SD 8.1) days. GCV doses ranged
      from 100 to 1,000 mg/d, mean 370.6 (SD 254.2) mg/d. Clinical resistance to
      treatment was diagnosed in 5 patients (11.6%). We found a positive correlation of
      GCV treatment duration with natural logarithm of initial CMV viremia (r = 0.56; P
      = .0002) and of time in months to CMV infection with mean cyclosporine level (r =
      -0.74; P = .04) and GCV dose (r = -0.34; P = .03). The duration of GCV therapy
      was positively influenced by CMV load and tacrolimus administration and
      negatively by patient's age and male sex. CONCLUSIONS: Appearance of any symptoms
      occurring after transplantation, even nonspecific, should lead to diagnostics for
      CMV infection. The duration of treatment depends on the severity of the infection
      expressed by CMV viremia. Clinical resistance to GCV is not frequent, but it is
      an important transplantologic problem.

PMID- 25380869
TI  - Molecular analysis of carbapenem-resistant strains of Pseudomonas aeruginosa
      isolated from patients hospitalized in various transplantation wards between 2008
      and 2011.
AB  - BACKGROUND: Recent years have seen a concerning increase in the number of
      carbapenem-resistant Pseudomonas aeruginosa strains. P aeruginosa is one of the
      most dangerous factors causing nosocomial infections, and immunosuppressed
      patients constitute a special risk group. The purpose of our study was to conduct
      a molecular analysis of 22 clinical isolates of carbapenem-resistant P aeruginosa
      obtained between 2008 and 2011. MATERIALS AND METHODS: Metallo-beta-lactamase
      (MBL) phenotype tests were conducted. A polymerase chain reaction technique was
      used to detect VIM, IMP, NDM, and GIM carbapenemase-encoding genes. The minimum
      inhibitory concentrations were determined for imipenem, meropenem, and doripenem.
      Molecular typing was conducted with the use of restriction fragment length
      polymorphism/pulsed-field gel electrophoresis (RFLP-PFGE). RESULTS: Of the 22
      strains initially resistant to at least one carbapenem, we selected 18 that
      exhibited the MBL phenotype. Of those 18, we identified 15 strains expressing VIM
      carbapenemase-encoding genes. None of the other evaluated genes were detected.
      VIM-positive isolates exhibited higher levels of resistance than the other ones.
      The RFLP technique revealed 10 different PFGE types and 6 epidemic foci.
      Identical strains were isolated over the period of up to 3 years. CONCLUSIONS:
      The reason for resistance to carbapenems in the majority (68%) of P aeruginosa
      strains isolated at the evaluated hospital was the presence of VIM carbapenemase.
      It is safe to say that the VIM carbapenemase is responsible for a higher level of
      resistance than unidentified mechanisms. Carbapenem-resistant strains of P
      aeruginosa spread clonally within individual wards and are likely to be of
      hospital origin.

PMID- 25380870
TI  - Molecular and phenotypic characteristics of methicillin-resistant Staphylococcus
      aureus strains isolated from hospitalized patients in transplantation wards.
AB  - OBJECTIVES: Hospital-acquired methicillin-resistant Staphylococcus aureus (HA
      MRSA) frequently causes therapeutic problems and provides information about the
      epidemiological condition of the ward. MATERIALS AND METHODS: HA-MRSA isolated
      from patients on transplantation wards in 1991, 1994, 1996, and from 2005 to 2007
      were compared using molecular methods such as restriction fragment length
      polymorphism-pulse field gel electrophoresis, multilocus sequence typing (MLST),
      multiplex polymerase chain reaction (PCR) for detection type of staphylococcal
      chromosomal cassette mec, and PCR for detection. RESULTS: The analysis covered HA
      MRSA strains, each from a different patient. All organisms were typed using
      molecular methods. MLST results were compared with an international base. The
      examined strains belonged to five different worldwide known clonal complexes: CC8
      (78%), CC5 (12%), CC1 (4%), CC30 (2%), and CC51 (4%). All could be recognized as
      representatives of a clonal complex CC8 clones: ST239-III (sequence type 239 and
      SCCmec type III named EMRSA-1, -4, -11, Brasilian, Hungarian) occurred with a
      frequency of 35.9%, ST254-IV (EMRSA-10, Hannover) occurred in 33.3%, ST247-I
      (EMRSA-5,-7, Iberian) occurred in 20.5%, ST241-III (Finland-UK) occurred in
      5.15%, and ST8-IV (EMRSA-2,-6) occurred in 5.15%. CONCLUSION: The predomination
      of different clones of HA-MRSA in the particular years was observed. In 1991, the
      EMRSA-10 (Hannover) clone predominated (53.3%). The Brasilian-Hungarian (EMRSA-1,
      -4, -11) clone predominated in 1994 (50%) as well as from 2005 to 2007 (41.3%),
      whereas in 1996 the Iberian clone was most frequent (53.9%).

PMID- 25380871
TI  - Evaluation of the prevalence of insertion element IS16 in vancomycin-resistant
      enterococci strains of Enterococcus faecium isolated from transplantology
      patients from a Warsaw Hospital between 2010 and 2012.
AB  - The study included 79 vancomycin-resistant Enterococcus faecium (VRE) strains
      isolated from 33 patients after kidney (n = 19) or liver (n = 14)
      transplantation; these patients were hospitalized between 2010 and 2012. The
      strains were obtained from infected persons as well as from carriers. All
      examined strains were tested for the susceptibility to antimicrobials active
      against enterococci and for the presence of vanA and vanB genes as well as the
      presence of the insertion sequence IS16 considered as one of the markers of
      hospital-associated strains. All 79 VRE strains of E faecium possessed IS16 and
      the vanA (vanB-negative) determinant. All tested strains were resistant to at
      least three groups of drugs; therefore, they were recognized as multidrug
      resistant. All isolates were resistant to glycopeptides, ampicillin, and most
      were resistant to tetracyclines, macrolides, nitrofurans, and high concentrations
      of aminoglycosides. The presence of insertion element IS16 and multiple
      resistance determinants prove that strains colonizing or infecting solid organ
      recipients were typical nosocomial pathogens.

PMID- 25380872
TI  - Specific character of anaerobic bacterial infections in patients treated in
      transplantation wards at one of the clinical hospitals in Warsaw.
AB  - Immunocompromised patients and patients undergoing invasive procedures are
      predisposed to bacterial infections, due to the possibility of micro-organism
      translocation from their physiological habitat. Infectious complications may
      occur both in the early and late post-transplantation periods. The purpose of
      this study was to evaluate the proportion as well as susceptibility profiles of
      obligatory anaerobes in the etiology of infections in patients hospitalized at
      transplantation wards of a large clinical hospital in Warsaw. A total of 104
      strains of obligatory anaerobes derived from patients hospitalized in two
      transplantation clinics at a clinical hospital in Warsaw were evaluated. The
      strains were isolated from 87 clinical samples collected from 84 patients of two
      transplantation wards between 2007 and 2012. A total of 104 obligatory anaerobic
      bacterial strains were isolated and identified, with Gram-positive and Gram
      negative bacteria constituting 60.6% and 39.4% of the isolates, respectively.
      Almost exclusively non-spore-forming anaerobes were detected in evaluated
      samples. The present study showed all isolated Gram-positive bacteria to be
      susceptible to beta-lactam antibiotics. Metronidazole-resistant bacteria were
      found among the genera Propionibacterium and Actinomyces. All Gram-negative rods
      were susceptible to imipenem and metronidazole. Among them, Bacteroides spp. and
      Parabacteroides distasonis showed resistance to penicillin G (100%). Because of
      their pathogenicity and altered antibiotic susceptibility profiles, the bacteria
      of the genera Bacteroides and Parabacteroides are of greatest clinical
      importance. Approximately 25% of isolates exhibit also resistance to clindamycin.
      Because of the growing rates of clindamycin resistance, the role of metronidazole
      in the treatment of Bacteroides spp. is of increasing importance.

PMID- 25380873
TI  - Blood infections in patients treated at transplantation wards of a clinical
      hospital in Warsaw.
AB  - Establishment of the etiology in blood infection is always advisable. The purpose
      of this study was to evaluate the proportion of different bacterial species,
      including aerobic and anaerobic bacteria in blood cultures of patients
      hospitalized in transplantation wards of a large clinical hospital between 2010
      and 2012. A total of 1994 blood samples from patients who were treated at one of
      two transplantation wards of a large hospital in Warsaw were analyzed using an
      automated blood culture system, BacT/ALERT (bioMerieux, France). The 306
      bacterial strains were obtained from the examined samples. The highest proportion
      were bacteria from the family Enterobacteriaceae (112 strains; 36.6%) with
      Escherichia coli (61 strains), Klebsiella pneumoniae (30 strains), and
      Enterobacter cloacae (10 strains) most commonly isolated. The non-fermenting
      bacilli constituted 21.6% (66 strains), with most common Stenotrophomonas
      maltophilia (31 strains), Pseudomonas aeruginosa (14 strains), Achromobacter spp.
      (12 strains), and Acinetobacter baumannii (3 strains). Most frequent Gram
      positive bacteria were staphylococci (25.2%). Of 77 staphylococcal strains, 56
      were coagulase-negative staphylococci and 21 Staphylococcus aureus. Other Gram
      positive bacteria included enterococci (14 strains) and Streptococcus pneumoniae
      (1 strain). Obligatory anaerobic bacteria were represented by 19 strains (6.2% of
      total isolates). Among all Enterobacteriaceae, 49 isolates (43.7%) produced
      extended-spectrum beta-lactamases (ESBLs). Resistance to methicillin was detected
      in 62% of S aureus isolates and in 46% of coagulase-negative staphylococci. Of 14
      enterococci cultured from blood samples, 2 strains (14.3%) were resistant to
      vancomycin. Both were Enterococcus faecium. Resistant strains of Gram-negative
      and Gram-positive bacteria are significant problems for patients in the
      transplantation ward.

PMID- 25380874
TI  - Glomerular filtration rate estimation in prospective living kidney donors:
      preliminary study.
AB  - INTRODUCTION: Kidney transplantation prolongs life expectancy in end-stage renal
      disease patients at a lesser cost than dialysis. Estimation of kidney function is
      crucial in the evaluation of prospective living kidney donors. Although
      unsurpassed in their precision methods of glomerular filtration rate (GFR)
      measurement with exogenous substances are invasive, expensive, and carry a risk
      for anaphylactic reactions. Alternatively, kidney function can also be assessed
      by GFR estimation formulas based on serum creatinine or novel markers such as
      cystatin C or beta-trace protein (BTP). The aim of this study was to compare the
      performance of GFR estimation methods with reference scintigraphy-measured GFR in
      population of living kidney donor candidates. METHODS: We included 25 prospective
      kidney donors (aged 28-64 years) and measured GFR with the following equations:
      Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Mayo Clinic,
      Nankivell, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; including
      cystatin C), and BTP based. GFR were assessed by (99)mTc-DTPA for reference. All
      estimation methods were compared with a reference by general linear models.
      RESULTS: The precision of GFR estimation by all methods is unsatisfactory (30%
      margin of reference held in <50% of cases). Direction of regression coefficients
      is negative for some of the methods even when adjusted for body mass index (BMI).
      Of the study subjects, 64% were overweight/obese. BMI value is significantly
      correlated with measured GFR (P < .01). CKD-EPI estimation equations are the most
      precise methods of GFR estimation in this analysis; in addition, CKD-EPI cystatin
      C and combined creatinine/cystatin C estimators are robust to overweight/obesity.
      CONCLUSIONS: The precision of GFR estimation is unsatisfactory, in part because
      of overweight, which adversely influences measured GFR, but also renders
      estimation methods unusable, except for CKD-EPI cystatin C and combined
      creatinine/cystatin C formulae. GFR measurement with exogenous substances remains
      the method of choice in the assessment of kidney function in prospective kidney
      donors. In addition, it provides useful information on differential (split) renal
      function.

PMID- 25380875
TI  - Kidney transplantation does not increase the level of basic hope or life
      satisfaction compared with hemodialysis in patients with chronic kidney disease.
AB  - INTRODUCTION: Although renal replacement therapy can lead to improved health, it
      also can cause emotional disturbances in patients. It is believed that the
      success of renal replacement therapy hinges not only on medical parameters, but
      also on psychosocial factors, which is why modern medicine provides an ever
      increasing role in the improvement of patients' quality of life. PURPOSE: The
      purpose of this study was to compare the level of life satisfaction, purpose in
      life, and basic hope in patients who had received renal replacement due to
      chronic kidney disease. We also tested whether the specific type of renal
      replacement therapy and kidney function parameters were influential factors on
      the above variables. PATIENTS AND METHODS: Sixty-one adult patients treated via
      renal replacement for chronic kidney disease took part in the study. Patients
      were divided into two groups: 31 hemodialysis patients (15 women and 16 men, ages
      23-77 years, mean 51.19 years, SD 14.53 years) and 30 patients who had undergone
      kidney transplantation (14 women and 16 men, ages 22-69 years, mean 48.40 years,
      SD 12.64 years). The following research tools were used for analysis:
      Satisfaction With Life Scale (SWLS), Purpose in Life Test (PIL), and Basic Hope
      Inventory (BHI-12). RESULTS: There were no statistical differences in the level
      of satisfaction with life between hemodialysis patients and postkidney transplant
      patients. The results for the SWLS obtained from both groups fell within the
      normal range. The average SWLS for hemodialysis patients remained 20.61, SD =
      5.79; for postkidney transplant patients, it was 22.57, SD = 5.16. The PIL level
      in the group of hemodialysis patients (101.5, SD = 15.64) was significantly lower
      than in the group of postkidney transplant patients (109.7, SD = 15.54). The
      average BHI-12 level was similar in both groups. The average BHI-12 result for
      hemodialysis patients was 29.00 (SD = 5.06), and for postkidney transplant
      patients 29.93 (SD = 3.55). The correlations between the psychological variables
      and selected biochemical parameters are worthy of particular attention. Among
      hemodialysis patients, there was an additional correlation between SWLS and
      hematocrit; whereas for postkidney transplant patients, there was an additional
      correlation of PIL and eGFR. CONCLUSIONS: Our data show that satisfaction with
      life and basic hope do not increase in patients after renal replacement therapy.
      The form of renal replacement therapy (hemodialysis or kidney transplantation)
      does not change the above variables. Patients treated via renal replacement
      require specialized psychological support to improve the efficacy of renal
      replacement therapy.

PMID- 25380876
TI  - No effect of pretransplantation bilateral nephrectomy on the resistive indices
      measured in the kidney allograft.
AB  - BACKGROUND: The cirrhotic kidney is the cause of sympathetic nervous system and
      the renin-angiotensin system activation leading to increased vascular resistance
      and arterial hypertension. The impact of unilateral or bilateral nephrectomy (UN
      or BN) performed before kidney transplantation on kidney graft intrarenal
      resistance has not been assessed yet. The aim of this study is to assess the
      intrarenal resistance parameters measured by Doppler ultrasound in the
      transplanted kidney in either nephrectomized or non-nephrectomized kidney
      transplant recipients. METHODS: Among 686 consecutive successful first cadaveric
      kidney graft recipients transplanted from 1998 to 2012, we identified 43 patients
      who underwent BN and 49 patients who underwent UN. Patients with acute rejection
      episodes within an early post-transplantation period were excluded. We have
      analyzed both pulsatility (PI) and resistance (RI) indices measured within the
      kidney graft before discharge from the hospital. RESULTS: The prevalence of
      hypertension in the follow-up period after transplantation was significantly
      lower in the BN group (65.1% versus 81.0% in other groups). Neither BN nor UN
      influenced the PI or RI values. The mean PI and RI values were 1.50 (1.38-1.61)
      and 0.75 (0.73-0.78) in BN, 1.48 (1.37-1.58) and 0.76 (0.73-0.79) in UN, and 1.47
      (1.43-1.50) and 0.74 (0.73-0.75) in non-nephrectomized patients, respectively.
      The results of multivariate analysis confirmed the lack of influence of
      nephrectomy on kidney graft resistive indices. CONCLUSION: BN before
      transplantation resulted in lower frequency of hypertension, but it did not
      affect the intrarenal vascular resistance measured in the kidney graft.

PMID- 25380877
TI  - Analysis of specificity of anti-human leukocyte antigen antibodies in kidney
      recipients in reference to clinical outcome.
AB  - BACKGROUND: Anti-human leukocyte antigens antibodies (HLA) are not always the
      main cause of graft injury but can be a marker of immune response to the graft.
      The aim of this study was to analyze anti-HLA specificities with the use of the
      most sensitive detection method (Luminex) in reference to clinical condition.
      METHODS: Sera of 65 kidney recipients (n = 443) were screened with the use of the
      mixed LABScreen kit, and, for 47 recipients, sera with maximal normalized
      background ratio (NBG) were subjected to specificity testing. NBG, numbers of
      specificities, donor-specific antibodies (DSA), and normalized mean fluorescence
      index (nMFI) of DSA and maximal anti-HLA were analyzed in reference to clinical
      (acute rejection [AR] diagnosis, immunosuppression), histopathological (C4d
      staining, chronic allograft nephropathy, AR type), and laboratory parameters
      (creatinine). RESULTS: We observed 1 to 51 specificities, class I DSA in 26.7%,
      class II in 10%, and estimated DQ-DSA in 63.3% of tested patients. Patients with
      AR and humoral AR had significantly higher NBG, number of anti-HLA class I, DQ
      and DQ-DSA types, and more frequently had anti-HLA and class II DSA-positive sera
      (P < .052). C4d staining was associated with higher anti-HLA class I (P = .053)
      and class I DSA (P = .002) type numbers, and maximal anti-HLA nMFI (P = .036) and
      was more frequent in AR (P = .048) and class II DSA positive patients (P = .046).
      Patients with chronic allograft nephropathy showed higher DQ-DSA-nMFI (P = .036).
      DQ-DSA-nMFI and maximal anti-HLA-nMFI correlated with creatinine increase
      (Spearman range [SR] = 0.64, SR = 0.41). Together with NBG, maximal class I and
      class II anti-HLA-nMFI correlated with the number of transplantation and maximal
      panel-reactive antibodies ratio (SR = 0.19-0.40). CONCLUSIONS: Anti-HLA detection
      allows for humoral AR diagnosis but also for identification of patients with risk
      of any rejection. However, clear rules of anti-HLA interpretation and studies on
      their clinical impact are needed.

PMID- 25380878
TI  - A significant role for anti-human leukocyte antigen antibodies and antibody
      mediated rejection in the biopsy-for-cause population.
AB  - The role of anti-human leukocyte antigen (HLA) antibodies and antibody-mediated
      rejection is well known, but our comprehension and the preventive measures we
      take seem to be insufficient. One of the major causes of premature renal
      transplant loss is recepients' immunologic hyperactivity to donors' antigens.
      Monitoring of humoral alloreactivity gives hope for early diagnosis and adequate
      therapy. The goal of our analysis was the assessment of the influence of anti-HLA
      antibodies on the function and survival of transplants. In our study we included
      60 consecutive renal transplant recipients who had a renal transplant biopsy-for
      cause performed due to insufficiency. Transplant biopsies were performed between
      the 7th day and 12th year (median, 2 years) after transplantation. Anti-HLA
      antibodies were present in 20 patients (33%). The patients were divided into 2
      groups according the presence of anti-HLA antibodies. In a 12-month observation,
      10/20 (50%) patients in the anti-HLA(+) group returned to dialysis in contrast
      with 7/40 (17.5%; P = .014) in the anti-HLA(-) group. Also, 8/10 (80%) of the
      anti-HLA(+) patients who lost the transplant had anti-HLA Abs class II and only
      2/10 (20%) had anti-HLA Abs class I. Anti-HLA antibodies were specific to a donor
      (donor-specific antibodies [DSA]) in 8/10 (80%) of the patients who lost the
      transplant. Anti-HLA antibodies appeared de novo in 50% of patients who lost the
      transplant. Nonadherence was suspected in 50% of patients. Acute humoral
      rejection occurred in 1 patient. Also, 8/10 (90%) developed chronic active
      humoral rejection. Our study revealed that graft loss in the renal transplant
      biopsy-for-cause population with the presence of anti-HLA Abs during a 12-month
      observation reached 50%. Nonadherence in these patients was very high and
      amounted to 50%. Monitoring of renal transplant recipients and individualization
      of therapy considering humoral activity should prolong renal graft survival.

PMID- 25380879
TI  - Non-HLA antibodies: angiotensin II type 1 receptor (anti-AT1R) and endothelin-1
      type A receptor (anti-ETAR) are associated with renal allograft injury and graft
      loss.
AB  - INTRODUCTION: Non-HLA antibodies specific for angiotensin II type 1 receptor
      (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells
      activate signaling pathways leading to cell proliferation and vascular injury.
      The aim of this study was to evaluate the impact of non-HLA antibodies on kidney
      allograft morphology and function in patients who underwent a kidney biopsy due
      to renal function impairment. PATIENTS AND METHODS: The study included 65
      consecutive renal transplant patients who were evaluated for the presence of non
      HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre
      transplant CDC cross-match were negative. A kidney allograft biopsy was performed
      between 6 days and 13 years (42 +/- 49 months) after transplantation, and the
      diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti
      AT1R and anti-ETAR antibodies was considered high. RESULTS: A high level of non
      HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients
      at the time of biopsy. Graft loss in the non-HLA-positive patients was
      significantly higher (71% in non-HLA-positive cases after 7.8 +/- 2.6 months vs
      11% after 6 months in non-HLA-negative cases [P = .00099]). In these non-HLA
      positive patients, the mean anti-AT1R level was 15.3 +/- 9.4 U/L and the mean
      anti-ETAR level was 13.8 +/- 8.6 U/L. In only 2 of these patients were anti-HLA
      antibodies additionally detected: anti-class I in 1 and anti-class II in both
      patients. The mean serum creatinine level was 2.34 +/- 0.6 mg/dL at the time of
      biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade
      IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in
      the remaining 6 patients. C4d was present in 3 of 7 patients. CONCLUSIONS: High
      levels of anti-AT1R and/or anti-ETAR antibodies were associated with
      morphological and functional allograft injury and graft loss in these study
      patients. Non-HLA antibodies can be helpful in assessing the risk of graft
      failure.

PMID- 25380880
TI  - Adipokines and nutritional status in kidney transplant recipients.
AB  - BACKGROUND: Obesity and disturbances of adipokine concentrations are often
      recognized in kidney transplant recipients (KTRs). Leptin plays a key role in
      regulating energy intake and expenditure, including appetite and hunger,
      metabolism, and behavior. Adiponectin modulates certain metabolic processes,
      including glucose regulation and fatty acid oxidation, and exerts some weight
      reduction effects. Visfatin has various functions, including the promotion of
      vascular smooth muscle cell maturation and inhibition of neutrophil apoptosis. It
      also activates insulin receptors and has insulin-mimetic effects, lowering blood
      glucose and improving insulin sensitivity. The aim of this study was to evaluate
      the prevalence of leptin, adiponectin, and visfatin and nutritional status
      abnormalities in stable KTRs. METHODS: Eighty KTRs aged 52.4 +/- 14.0 years
      participated in the study. Nutritional status was determined with the use of the
      7-point Subjective Global Assessment (SGA), anthropometric measurements
      (bioimpedance analysis), and serum concentration. Concentrations of leptin,
      adiponectin, and visfatin were measured with the use of enzyme-linked
      immunosorbent assay. RESULTS: Mean time after transplantation and estimated
      glomerular filtration rate (eGFR; Modification of Diet in Renal Disease formula)
      were 82.5 +/- 56.5 months and 42.0 +/- 15.0 mL/min/1.73 m(2), respectively; 29
      (36.2%) of the KTRs, despite high body mass index (BMI >=25 kg/m(2)), presented
      mild malnutrition (SGA <=5). BMI, content of body fat, and leptin concentration
      correlated positively with time from transplantation and negatively with eGFR.
      Additionally, patients with BMI >=25 kg/m(2) presented significantly higher
      leptin-to-adiponectin ratios compared with lean patients (3.5 vs 1.1,
      respectively; P < .05). KTRs with eGFR >=60 mL/min/1.73 m(2) presented
      significantly lower leptin concentration and BMI. CONCLUSIONS: Despite high BMI,
      mild malnutrition was present in one-third of KTRs. Increased BMI, abdominal
      obesity, and high leptin concentration were aggravated by time from
      transplantation and deterioration of graft function. Overweight/obesity and
      incorrect leptin-to-adiponectin ratio could increase cardiovascular risk in KTRs.

PMID- 25380881
TI  - Nutritional status and carnitine level in kidney transplant recipients.
AB  - INTRODUCTION: Overweight/obesity, malnutrition, and abnormalities in carnitine
      metabolism are recognized in kidney transplant recipients (KTRs). AIM: The aim of
      this study was to evaluate the prevalence of nutritional abnormalities and
      carnitine status in KTRs. METHODS: The study was performed in 80 stable KTRs aged
      52.4 +/- 14.0 years, without carnitine supplementation. Nutritional status was
      determined using a 7-point Subjective Global Assessment, anthropometric
      measurements, and s-albumin level. Urinary excretion and serum concentration of
      total (TC), free (FC) carnitine were measured using enzymatic methods according
      to Cederblad. RESULTS: Mean transplantation vintage and estimated glomerular
      filtration rate (Modification of Diet in Renal Disease; 4 points) were 82.5 +/-
      56.5 months and 42.0 +/- 15.0 mL/min/1.73 m(2), respectively. Overweight and
      obesity were noticed in 41% and 14% of patients, respectively. Signs of
      malnutrition were present in 64% (21/33) of the overweight patients, and in 91%
      (10/11) of the obese patients. KTRs with malnutrition (Subjective Global
      Assessment <=5) were significantly older, with longer transplantation vintage,
      lower eGFR, higher body mass index (BMI), higher body fat, and decreased hand
      grip strength in comparison to KTR with good nutritional status (Subjective
      Global Assessment >5). In 8.6% of KTRs, deficiency of FC (in serum and urine) was
      observed. Carnitine (TC and FC) and FC/TC ratio were not correlated with
      anthropometric and laboratory parameters of nutritional status. Serum of TC and
      FC concentrations negatively correlated with graft function. CONCLUSIONS: Plasma
      carnitine deficiency (limited availability) can appear in the KTR group and does
      not correspond with signs of both malnutrition and obesity. In spite of
      overweight/obesity, KTRs showed features of malnutrition and they need thorough
      nutritional evaluation and appropriate nutritional interventions.

PMID- 25380882
TI  - Vitamin B6 status, immune response and inflammation markers in kidney transplant
      recipients treated with polyclonal anti-thymocyte globulin.
AB  - BACKGROUND/OBJECTIVES: Vitamin B6 status has an impact on the body's inflammatory
      and immune responses. Immunosuppressive therapy may influence vitamin B6
      metabolism in kidney transplant recipients. Treatment with polyclonal anti
      thymocyte globulin (ATG) is associated with long-term changes in inflammatory and
      immune parameters. It is not known if ATG therapy also may have an impact on
      vitamin B6 status in kidney transplant recipients. We aimed to analyze the impact
      of therapy with ATG on vitamin B6 status, immune response, and the profile of
      inflammatory cytokines. SUBJECT/METHODS: This was a retrospective, observational
      study that included 44 kidney allograft recipients. Twenty patients received
      induction therapy with ATG (6 to 24 months before enrollment). Twenty-four
      patients constituted the control group, matched with respect to time since
      transplantation. The B6 vitamers, total lymphocyte count, CD3 percentage,
      interleukin (IL)-6, -7, and -10, transforming growth factor beta, interferon
      gamma, and chemokine ligand 21 were analyzed in a study group. RESULTS: All
      indicators of vitamin B6 status were lower in the ATG group than in the control
      group. There were also significant differences with respect to immune response
      (significantly lower total lymphocyte count and CD3 in the ATG group) and
      inflammatory status (significantly higher IL-6 and IL-10 in the ATG group).
      Vitamin B6 vitamers and derivatives were not related to lymphocyte count and
      cytokine levels or to estimated glomerular filtration rate and age of the study
      population. CONCLUSIONS: Vitamin B6 stores and active forms are lower in kidney
      transplant recipients treated with ATG. ATG therapy promotes CD3 and total
      lymphocyte depletion and increases indicators of inflammation. We found no
      associations between vitamers of B6, immune response cells, and inflammatory
      cytokines in study population.

PMID- 25380883
TI  - Increased plasma matrix metalloproteinase-2 (MMP-2), tissue inhibitor of
      proteinase-1 (TIMP-1), TIMP-2, and urine MMP-2 concentrations correlate with
      proteinuria in renal transplant recipients.
AB  - BACKGROUND: The most frequent cause of kidney allograft loss is chronic allograft
      injury, often with proteinuria as the clinical feature. Occurrence of proteinuria
      late after kidney transplantation is associated with worse graft function and
      patient survival. AIM: The aim of the study was to assess plasma and urine matrix
      metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases
      (TIMP-1 and TIMP-2) in proteinuric renal transplant recipients (RTRs). The
      factors were determined by enzyme-linked immunosorbent assay in 150 RTRs (51
      women and 99 men), aged 49.2 +/- 11.5 years, at mean 73.4 +/- 41.2 months after
      kidney transplantation (range: 12 to 240 months). RESULTS: Proteinuric RTRs
      compared with non-proteinuric RTRs had higher median plasma MMP-2 (P = .012),
      TIMP-1 (P = .0003), and TIMP-2 (P = .0021) concentrations, as well as higher
      urine MMP-2 (P < .0001) excretion. The presence of proteinuria had no impact on
      plasma MMP-9 and urine MMP-9, TIMP-1, and TIMP-2. Proteinuria and estimated daily
      proteinuria (uPr:uCr) correlated positively with plasma MMP-2 (rs = 0.226, P =
      .0054 and rs = 0.241, P = .003), TIMP-1 (rs = 0.305, P = .00015 and rs = 0.323, P
      = .000055), TIMP-2 (rs = 0.273, P = .0007 and rs = 0.269, P = .001) and urine MMP
      2 (rs = 0.464, P < .0001 and rs = 0.487, P < .0001), respectively. Proteinuric
      RTRs had impaired graft function with higher median serum creatinine
      concentrations (1.91 [1.60-2.43] mg/dL versus 1.41 [1.20-1.65] mg/dL, P < .00001)
      and lower estimated glomerular filtration rate (36 [28-45] mL/min/1.73 m(2)
      versus 53 [43-61] mL/min/1.73 m(2), P < .00001) than RTRs without proteinuria.
      CONCLUSIONS: Our research revealed that in RTRs, proteinuria was significantly
      associated with increased concentrations of enzymes involved in extracellular
      matrix (ECM) degradation: plasma MMP-2, TIMP-1, TIMP-2, and urine MMP-2. Findings
      strongly emphasize increased plasma TIMPs in proteinuric RTRs that inhibit
      degradation of ECM by MMPs and favor excessive deposition of ECM proteins.

PMID- 25380884
TI  - Advanced age of renal transplant recipients correlates with increased plasma
      concentrations of interleukin-6, chemokine ligand 2 (CCL2), and matrix
      metalloproteinase 2, and urine concentrations of CCL2 and tissue inhibitor of
      metalloproteinase 1.
AB  - BACKGROUND: Advanced age of renal transplant recipients (RTRs) has a negative
      impact on kidney allograft survival through impaired extracellular matrix
      degradation by the matrix metalloproteinases/tissue inhibitors of
      metalloproteinases (MMPs/TIMPs) system. Moreover, older RTRs are at risk of
      smoldering inflammation, known as inflammaging. AIM: The aim of the study was to
      assess the impact of a RTR's age on plasma and urine concentrations of
      interleukin 6 (IL-6), chemokine ligand 2 (CCL2), and the MMPs/TIMPs system.
      MATERIAL AND METHODS: One hundred fifty adult RTRs (8.7% >= 65 years) and 37
      adult healthy volunteers (10.8% >= 65 years) were enrolled in the study. The
      studied factors (IL-6, CCL2, MMP-2, MMP-9, TIMP-1 and TIMP-2) were quantified in
      plasma and urine with enzyme-linked immunosorbent assay. The Mann-Whitney U test
      and Spearman's (rs) rank correlation were applied, and differences with a P < .05
      were considered statistically significant. RESULTS: There was a weak but
      significant positive correlation between increasing RTR's age and plasma IL-6 (rs
      = 0.18, P = .028), CCL2 (rs = 0.27, P = .001), and MMP-2 (rs = 0.20, P = .017),
      as well as urine CCL2 (rs = 0.16, P = 0.050) and TIMP-1 (rs = 0.20, P = .014)
      concentrations. CONCLUSIONS: Advancing age of RTRs correlates with increasing
      plasma IL-6 and CCL2 concentrations, reflecting smoldering inflammation (known as
      inflammaging) and alterations in MMPs/TIMPs profiles, especially with increased
      plasma MMP-2 and urine TIMP-1 concentrations.

PMID- 25380885
TI  - Zonulin, iron status, and anemia in kidney transplant recipients: are they
      related?
AB  - BACKGROUND: In patients after kidney transplantation, anemia is relatively common
      and is associated with impaired kidney function, subclinical inflammatory state,
      and immunosuppressive treatment. Zonulin-prehaptoglobin-2, a newly discovered
      protein, is necessary for integrity of intracellular tight junctions in the gut.
      Taking into consideration iron metabolism, including its absorption in the gut,
      we designed a cross-sectional study to look for the possible interactions among
      zonulin, iron status, and anemia in kidney transplant recipients. METHODS: The
      study was performed on 72 stable kidney transplant recipients and 22 healthy
      volunteers. Zonulin, iron status, and inflammatory markers were assessed with the
      use of commercially available kits. RESULTS: Zonulin was significantly lower in
      kidney allograft recipients than in healthy volunteers (P < .001). Zonulin
      correlated with systolic blood pressure (r = -0.33; P < .05), thyroid-binding
      globulin (r = 0.24; P < .05), hematocrit (r = 0.28; P < .005), hemoglobin (r =
      0.32; P < .01), total protein (r = -0.33; P < .01), erythrocyte count (r = 0.26;
      P < .05), and fasting glucose (r = -0.25; P < .05). Zonulin was not affected by
      sex, type of immunosuppressive therapy, presence of diabetes, coronary artery
      disease, heart failure, hypertension, or cause of end-stage renal disease.
      Zonulin was not related to any of the iron parameters studied. In multiple
      regression analysis, predictors of zonulin were total protein and thyroglobulin
      binding protein, explaining 46% of variation. CONCLUSIONS: Zonulin, with its
      poorly defined function, does not seem to play a role in the anemia in kidney
      allograft recipients; however, it seems to be related to the absorption process
      in the gut.

PMID- 25380886
TI  - FGF23 and Klotho in relation to markers of endothelial dysfunction in kidney
      transplant recipients.
AB  - BACKGROUND: Fibroblast growth factor (FGF) 23 is a newly discovered member of the
      FGF family. Klotho is a cofactor of FGF23. Activation of the FGF23-Klotho system
      is responsible for negative phosphate balance. In addition, FGF23 appears to be a
      risk factor for cardiovascular complications. The aim of this study was to assess
      levels of FGF23 and Klotho in stable kidney transplant recipients on triple
      immunosuppressive therapy in relation to comorbidities and markers endothelial
      dysfunction. Healthy volunteers served as a control group. METHODS: Hemoglobin,
      urea, and creatinine were studied with the use of standard laboratory methods in
      the hospital central laboratory. We assessed FGF23 and Klotho, markers of
      endothelial function/injury von Willebrand factor (vWF), intercellular adhesion
      molecule (ICAM), vascular cell adhesion molecule (VCAM), and interleukin (IL) 6,
      N-terminal pro-B-type natriuretic peptide (NT-proBNP) and copeptin with the use
      of commercially available assays. RESULTS: FGF23 was significantly higher and
      Klotho significantly lower in kidney transplant recipients compared with healthy
      volunteers. FGF23 correlated with copeptin (r = 0.28; P < .05), IL-6 (r = 0.39; P
      < .01), VCAM (r = 0.36; P < .01), time after transplantation (r = 0.31; P < .05),
      platelet count (r = 0.31; P < .05), mean corpuscular volume (r = -0.40; P < .01),
      and phosphate (r = 0.31; P < .05). Klotho correlated with NT-proBNP (r = 0.38; P
      < .01), vWF (r = -0.26; P < .05), calcium (r = -0.39; P < .01), and age (r =
      0.45; P < .001). FGF23 was significantly higher and Klotho significantly lower in
      patients with estimated glomerular filtration rate (eGFR) >60 mL/min compared
      with patients with eGFR <60 mL/min. CONCLUSIONS: Disturbances in the FGF23-Klotho
      system appeared to be related to the endothelial cell injury. Thus they are
      involved not only in pathogenesis of the metabolic bone disease but also in
      cardiovascular complications, particularly in kidney disease.

PMID- 25380887
TI  - YKL-40, a marker of cardiovascular disease and endothelial dysfunction, in kidney
      transplant recipients.
AB  - BACKGROUND: YKL-40 is an inflammatory glycoprotein involved in endothelial
      dysfunction and expressed in macrophages in the earliest lesion of
      atherosclerosis. Because cardiovascular mortality is the main cause of death,
      there are no data on kidney transplant recipients, so the aim of the study was to
      assess YKL-40 in that population, with particular attention being paid to the
      relationship with endothelial damage. METHODS: We studied 68 patients after
      kidney transplantation. Complete blood count, creatinine, lipids, and fasting
      glucose were studied with the use of standard laboratory methods. We assessed YKL
      40; markers of inflammation high-sensitivity C-reactive protein (hs-CRP), von
      Willebrand factor, thrombomodulin, interleukin-6, intracellular adhesion
      molecule, and vascular cell adhesion molecule; markers of hemostasis plasmin
      antiplasmin complexes, thrombin-antithrombin complexes, prothrombin fragments
      1+2; and marker of kidney function neutrophil gelatinase-associated lipocalin
      (NGAL) with the use of commercially available assays. RESULTS: Mean levels of YKL
      40 were significantly higher in kidney allograft recipients than in the control
      group (P < .001). YKL-40 was also significantly higher in patients with coronary
      artery disease, hypertension, and diabetes compared with their counterparts
      without these diseases. YKL-40, in univariate analysis, was related to NGAL,
      protein Z, plasmin-antiplasmin complex, mean corpuscular volume, cyclosporine
      level, and hs-CRP. YKL-40 was not related to serum lipids, markers of endothelial
      cell injury, or causes of end-stage renal failure. YKL-40 was predicted by
      cyclosporine level, NGAL, and hs-CRP, explaining 37% of the variation.
      CONCLUSIONS: Elevated YKL-40 may contribute to enhanced risk of cardiovascular
      complication, mainly owing to endothelial cell injury and inflammation in
      patients after kidney transplantation treated with calcineurin inhibitors.

PMID- 25380888
TI  - Preemptive kidney transplantation: analysis of kidney grafts from the same donor.
AB  - BACKGROUND: From November 2003 to December 2012, in the Gdansk Center, 64
      patients received preemptive transplantation (PET). PET comprised 8% of 794
      kidney transplantations performed during this time. The benefits for individual
      patients and for the health care system are discussed. METHODS: This study
      compares the outcomes of these PET patients who had their kidney pairs
      transplanted after a variable duration of dialysis (PTD), a total of 51 pairs.
      RESULTS: The mean Charlson comorbidity index was 2.57 vs 3.04 (P > .05) for the
      PET and PTD groups, respectively. Both groups did not differ significantly with
      respect to 1-year patient and graft survivals, and incidences of acute rejection.
      Five (9.8%) PET patients and 20 (39%) PTD patients experienced delayed graft
      function (P < .05). The graft function (serum creatinine/4p MDRD) 1 year after
      transplantation was similar in both groups (1.42/53.7 vs 1.43/57.4;
      mg/dL/mL/min/1.73 m(2)). More PET patients continued normal professional
      activities or education before and after transplantation (P < .05). CONCLUSIONS:
      Our single-center results confirmed that for both medical and socioeconomic
      reasons, PET is an optimal mode of renal replacement therapy.

PMID- 25380889
TI  - Epidemiology of posttransplantation chronic kidney disease can be altered by
      choice of formula estimating glomerular filtration rate.
AB  - BACKGROUND: Epidemiology of posttransplantation chronic kidney disease (CKDPT)
      has different characteristics than in the general population. Precise
      determination of glomerular filtration rate (GFR) is essential in the clinical
      decision making process as well as in management of a population that is based on
      epidemiological data. The aim of our study was to analyze the impact of an
      applied GFR estimation method on the epidemiology of CKDPT during the first year
      after transplantation. METHODS: We estimated GFR (eGFR) using the 4-variable
      Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) formula in 215 renal transplant recipients.
      We also measured and estimated creatinine clearance using the Cockroft-Gault (C
      G) formula. Based on these data, we analyzed the influence of these formulas on
      the epidemiology of CKDPT. RESULTS: The largest fraction of patients is in stage
      3 of CKDPT (40% to 62%). Application of the CKD-EPI formula instead of MDRD
      results in a decrease of prevalence of stage 3 by 3.9% at the early period (weeks
      2 to 8) and by 13.8% at the late period (weeks 9 to 52) after transplantation.
      This is coexistent with reclassification from stage 3B to 3A and 3A to stage 2.
      Use of a measured or C-G-based creatinine clearance instead of the MDRD formula
      results in decrease of prevalace of stage 3 by 16.5% and 13%, respectively, in
      the early period and by 32.5% or 27%, respectively, in the late period.
      CONCLUSIONS: Epidemiology of CKDPT depends on the method of calculation of eGFR.
      Application of creatinine clearance or the C-G formula results in an increase of
      prevalence of patients with better graft function.

PMID- 25380890
TI  - The modification of diet in renal disease and chronic kidney disease epidemiology
      collaboration formulas versus measured or estimated creatinine clearance in
      kidney transplant recipients.
AB  - BACKGROUND: Estimation of glomerular filtration rate (eGFR) after renal
      transplantation is performed with the use of methods that are standardized for a
      population of nontransplantation patients with chronic kidney disease. The aim of
      the study was to compare the performance of GFR estimation formulas in renal
      transplant recipients. METHODS: The Modification of Diet in Renal Disease (MDRD)
      and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were
      compared with measured creatinine clearance or clearance estimated by the
      Cockroft-Gault (C-G) formula. The influence of age, body mass index, and eGFR on
      the relative performance of these formulas also was studied by subgroups
      analysis. RESULTS: Mean measured or estimated creatinine clearance overestimates
      the values of GFR calculated using the MDRD or CKD-EPI equation. This was
      statistically significant (P < .05) in whole-study population and in subgroups of
      patients at age above 25 years, with body mass index above 25, and in a subgroup
      with eGFR-MDRD <50 mL/min/m(2). The mean bias from creatinine clearance was 7.46
      mL/min for MDRD, 4.4 mL/min for CKD-EPI and -1.65 mL/min for C-G formula. There
      was a statistically significant (P < .05) negative correlation between eGFR value
      and bias from creatinine clearance for all 3 methods of estimation. The
      correlation coefficient was -0.4 for MDRD, -0.36 for CKD-EPI, and -0.46 for C-G
      clearance. CONCLUSIONS: Measured and estimated creatinine clearance overestimate
      values of eGFR calculated by the MDRD or CKD-EPI formula in a population of
      kidney transplant recipients, especially in subjects with obesity and worse renal
      function. Accuracy of analyzed GFR estimation formulas decreases with
      deterioration of renal graft function.

PMID- 25380891
TI  - Pregnancy after kidney transplantation: a single-center experience and review of
      the literature.
AB  - After kidney transplantation (KT), pregnancy is possible, although the risk of
      maternal and fetal complications is much higher than in the general population.
      Outcome of 22 pregnancies in 17 patients transplanted in the Gdansk center in the
      period 1980-2012 was studied. Mean maternal age at pregnancy was 30 +/- 5 (range,
      23-39) years, interval between transplantation and conception 3.4 +/- 2.5 (range,
      0.6-11) years. Mean creatinine concentration before conception was 1.29 +/- 0.36
      (range, 0.8-2.45) mg/dL and was stable during 1 year preceding pregnancy (mean
      increase, 0.01 mg/dL). Nine of the 17 patients received 1 and 4 received >=2
      antihypertensive drugs, and 1 had proteinuria. Twelve of the 17 patients were
      primagravidas, 1 was pregnant 3 times, and 14 times. At the time of conception,
      20 patients received CNI (14 cyclosporine, 6 tacrolimus), 15 antimetabolites (3
      mycophenolate mofetil [MMF], 12 azathioprine), 1 mammalian target of rapamycin
      inhibitor (mTORi; sirolimus), and all prednisone. MMF and mTORi were discontinued
      before or during the 1st weeks of pregnancy. Maternal outcome: all survived the
      pregnancy. None experienced rejection or graft loss as a direct result of
      pregnancy. Maternal complications included edema (5/17), worsening of blood
      pressure control (5/17), and worsening (1/17) or new onset of proteinuria (2/17).
      Mean creatinine decrease during pregnancy was 0.06 mg/dL. Mean creatinine 1 year
      after pregnancy was 1.49 +/- 0.53 mg/dL. There were 12 cesarean sections. Fetal
      outcomes: 17 live births (2 with serious congenital defects), 2 spontaneous and 1
      induced abortion, 2 stillbirths. Mean pregnancy age and neonate birth weights
      were 35 +/- 4 (range, 23-39) weeks and 2,552 +/- 629 (range, 1,480-3,420) g,
      respectively. During mean 8.5 (range, 1-25) years of follow-up after pregnancy,
      4/17 patients lost grafts. Grafts were lost in the 3rd to 7th years after
      pregnancy. We conclude that pregnancy does not exert a direct negative influence
      on patient and graft survivals; 68% of all pregnancies resulted in delivering
      healthy neonates.

PMID- 25380892
TI  - Chronic allograft dysfunction in kidney transplant recipients: long-term single
      center study.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence and risk factors
      responsible for the occurrence and progression of chronic allograft dysfunction
      (CAD) among patients treated in our transplant center. MATERIAL AND METHODS:
      Retrospective analysis included 637 kidney allograft recipients transplanted
      between 1990 and 2003 with functioning graft for at least 1 year. CAD was
      diagnosed based on increased creatinine concentration >= 2 mg/dL, occurrence of
      proteinuria, and worsening of arterial hypertension. In immunosuppressive
      treatment, 50% of patients received cyclosporine A (CsA), azathioprine, and
      prednisone; 25% received CsA, mycophenolate mofetil (MMF), and prednisone;
      whereas 20% received tacrolimus, MMF, and prednisone. The influence of immune and
      non-immune factors before and after transplantation on the occurrence and
      progression of CAD was analyzed. RESULTS: CAD was diagnosed in 43.1% of patients
      within 10 years after kidney transplantation. CAD development considerably
      worsened the actual 10-year survival rate of patients (80% versus 92%) and the
      graft (42% versus 92%). The following factors had the greatest influence (as
      confirmed with multivariate regression analysis) on CAD progression: proteinuria
      (odds ratio [OR]: 11.3; P < .0001), serum creatinine concentration > 1.5 mg/dL at
      12th month (OR: 3.5; P < .0001) and 24th month (OR: 6.69; P < .0001),
      cytomegalovirus (CMV) infections (OR: 3.15; P < .0001), and male gender of
      recipients (OR: 1.48; P < .04). In the CAD patients, acute rejection episodes,
      delayed graft function, urinary tract infections, and hepatitis C virus (HCV)
      infections were statistically significantly more often observed compared with the
      group of patients with stable renal function (reference group). Moreover, in the
      CAD group, donors were older and recipients younger. The CAD patients had higher
      arterial pressure and uric acid concentration. CONCLUSIONS: During the 10-year
      follow-up, chronic renal allograft dysfunction developed in 43.1% of patients.
      Proteinuria, serum creatinine level >1.5 mg/dL at 12th and 24th month, and CMV
      infections were identified as the most significant CAD progression factors. CAD
      had detrimental effects both on graft and patient survival rates.

PMID- 25380893
TI  - Recipient uridine 5'-diphospho-glucuronosyltransferase UGT1A9 c.98T>C variant
      determines transplanted kidney filtration rate.
AB  - Mycophenolic acid preparations are commonly used in prophylaxis of kidney
      allograft acute rejection. The medication is metabolized by uridine diphosphate
      glucuronosyltransferases, mainly UGT1A9 present in liver, kidney, and intestine.
      The effect of UGT1A9 allelic variants on drug metabolism in healthy volunteers
      and transplant recipients has been previously evaluated; these studies included
      the UGT1A9 c.98T>C polymorphism (rs72551330, p.Met33Thr) causing methionine-to
      threonine substitution in the polypeptide chain. The study objective was to
      evaluate the relationship between UGT1A9 c.98T>C polymorphism and kidney graft
      function and survival and the risk of acute allograft rejection. Kidney
      recipients who underwent transplantation between 2000 and 2007 at the Medical
      University of Warsaw were included. Clinical data originated from standard
      medical records, UGT1A9 c.98T>C was genotyped using a polymerase chain reaction
      restriction fragment length polymorphism method. A group of 243 kidney transplant
      recipients was enrolled in the study. The frequency of the c.98C allele was 2.4%
      (12 of 486). Most of the carriers of the allelic variant (10 of 12) received
      cyclosporine A at transplantation. In the c.98C allele carriers, worse function
      of the renal allograft, manifested by a significantly lower glomerular filtration
      rate, was found in the first posttransplantation month and persisted at a lower
      level for 8 years after the procedure (for comparison of the UGT1A9 c.98 TT vs
      the UGT1A9 c.98 TC groups, P = .03). No association was found between the
      presence of the UGT1A9 c.98C allele and the risk of delayed renal graft function,
      acute rejection, dysfunction of the renal graft, or dialysis treatment
      reintroduction. Significantly lower estimated glomerular filtration rate of the
      renal allograft in UGT1A9 c.98C carriers did not translate into decreased
      allograft survival.

PMID- 25380894
TI  - Generic formulation of mycophenolate mofetil (Myfenax) in de novo renal
      transplant recipients: results of 12-month observation.
AB  - BACKGROUND: The aim of this study was to show the preliminary outcomes of
      transplantation in patients treated with the generic formulation of mycophenolate
      mofetil (Myfenax, Teva). MATERIALS AND METHODS: Over the past 4 years, 60
      patients received generic mycophenolate mofetil (Myfenax) after renal
      transplantation at the Gdansk Transplantology Center. During the same time
      period, another 273 kidney transplantations were performed in our department, and
      these patients were treated with other formulations of mycophenolate (CellCept
      [Roche], Myfortic, or mycophenolate mofetil-Apotex) as a part of the
      immunosuppressive plan. Thirty of the Myfenax patients received a pair of kidneys
      from the same donor and received original mycophenolate mofetil CellCept with
      observation for at least 12 months. RESULTS: The outcomes of the renal
      transplantations in both groups (Myfenax vs pair) were good, with satisfactory
      function of grafts. One case of graft loss was reported in the Myfenax group
      (renal vein thrombosis, graftectomy 5 days after transplantation). There was no
      difference in the incidence of acute renal graft rejection in either group.
      Moderate adverse reactions to immunosuppression were observed in both groups. On
      the other hand, a comparison between the 60 patients with Myfenax and the 273
      other patients with other formulations of mycophenolate revealed no differences
      in the incidence of acute renal graft rejection, delayed graft function, graft
      loss, and death. CONCLUSIONS: There were no differences in the incidence of acute
      renal graft rejection, delayed graft function, graft loss, and death in patients
      with Myfenax vs original CellCept and other formulations of mycophenolate. To
      confirm its complete biological and pharmacokinetic equivalence with the
      reference medicine, long-term, randomized observations carried out on larger
      renal transplant patients groups are needed.

PMID- 25380895
TI  - Impact of pretransplant body mass index on early kidney graft function.
AB  - BACKGROUND: An increase in the number of obese patients on transplantation
      waiting lists can be observed. There are conflicting results regarding the
      influence of body mass index (BMI) on graft function. METHODS: We performed a
      single-center, retrospective study of 859 adult patients who received a renal
      graft from deceased donors. BMI (kg/m(2)) was calculated from patients' height
      and weight at the time of transplantation. Kidney recipients were subgrouped into
      4 groups, according to their BMI: Groups A (<18.5; n = 57), B (18.6-24.9; n =
      565), C (25-29.9; n = 198) and D (>30; n = 39). Primary or delayed graft function
      (DGF), acute rejection (AR) episodes, and number of reoperations, graft function
      expressed by glomerular filtration rate (GFR) and serum creatinine concentration
      and number of graft loss as well as the recipient's death were analyzed. The
      follow-up period was 1 year. RESULTS: Obese patients' grafts do not develop any
      function more frequently in comparison with their nonobese counterparts (P <
      .0001; odds ratio [OR], 32.364; 95% CI, 2.174-941.422). Other aspects of the
      procedure were analyzed to confirm that thesis: Cold ischemia time and number of
      HLA mismatches affect the frequency of AR (OR, 1.0182 [P = .0029] and OR, 1.1496
      [P = .0147], respectively); moreover, donor median creatinine serum concentration
      (P = .00004) and cold ischemia time (P = .00019) are related to delayed graft
      function. BMI did not influence the incidence of DGF (P = .08, OR; 1.167; 95% CI,
      0.562-2.409), the number of AR episodes (P > .1; OR, 1.745; 95% CI, 0.846-3.575),
      number of reoperations, GFR (P = .22-.92), or creatinine concentration (P = .09).
      Number of graft losses (P = .12; OR, 1.8; 95% CI, 0.770-4.184) or patient deaths
      (P = .216; OR, 3.69; 95% CI, 0.153-36.444) were not influenced. CONCLUSION:
      Greater recipient BMI at the time of transplantation has a significant influence
      on the incidence of primary graft failure.

PMID- 25380896
TI  - Impaired kidney allograft: how long can it function? A single-center study of the
      transplantation population.
AB  - Impaired renal graft function is a matter of particular concern during post
      transplantation care because low estimated glomerular filtration rate (eGFR) is a
      risk factor for graft loss. The aim of the study was to assess risk factors for
      inferior outcomes of kidney transplantations with low eGFRs. We identified 72
      patients who underwent transplantation between 1999 and 2005 who had chronic
      renal graft dysfunction after 6 months post-transplantation (eGFR < 40
      mL/min/1.73 m(2)), received a kidney transplant between 1999 and 2005, and were
      treated in one center through the entire post-transplantation course. Three
      patients who were lost for follow up after 6.4, 6.7, and 8.5 years are not
      included in this analysis. A group of 23 patients (33%) had chronic kidney
      disease stage 4 (eGFR < 30 mL/min/1.73 m(2)) at 6 months. In 39 patients (56%),
      delayed graft function was diagnosed. Forty-eight patients (70%) had at least one
      episode of acute graft rejection. Results were confirmed using biopsy in 39
      patients. Eight patients (12%) died and 35 patients (51%) lost their grafts
      between 1.6 and 14 years (median, 6.3 years). The remaining 26 (38%) patients
      have still functioning allografts 11 years after transplantation (median). The
      initial immunosuppression included calcineurin inhibitor (CNI) in all cases. At
      the end of study, 6 (8.3%) patients received mammalian target of rapamycin
      inhibitor plus steroids, whereas the remaining were treated with CNIs.
      Improvement of kidney function by 15% was observed in 23% of the studied
      population between 6 and 24 months. This satisfactory outcome was a result of the
      careful follow-up examinations and comprehensive medical care provided by our
      dedicated staff of nurses and physicians. Improvement of kidney function may
      reflect a state of immune quiescence in some patients which allows them to
      sustain a functioning kidney despite injury. 

PMID- 25380898
TI  - Effect of recipient sensitization (peak panel reactive antibodies) on 15-year
      survival after kidney transplantation.
AB  - BACKGROUND: Despite dynamic development within the field of transplantology, the
      immunization of a potential organ recipient remains an important issue for
      transplant teams. Panel reactive antibodies (PRA) identification in the serum of
      the recipient remains routine practice in the majority of transplantation
      centers. The influence of peak PRA levels on graft function is a well known fact.
      The aim of this study was to determine the effect of peak PRA on long-term
      survival after renal transplantation. METHODS: The study was conducted on a group
      of 232 kidney recipients from multiorgan donors, transplanted in 6 transplant
      centers in Poland from 1995 to 1997. Data analyzed in this study included
      recipients' age, sex, PRA, HLA, number and time of hemodialyses after the
      transplantation, cold ischemia time, and etiology of end-stage renal disease. The
      effect of data examined in this study on mortality was evaluated at set time
      points at 5, 10, and 15 years after transplantation. The statistical methods
      included monofactorial and multifactorial Kaplan-Meier survival analysis and Cox
      proportional hazards model for mortality prediction. A P value of <.05 was
      considered to be statistically significant. RESULTS: Among all of the analyzed
      factors, only peak PRA concentrations significantly correlated with increased
      mortality among renal transplant recipients. The results were analyzed in all of
      the set time points: P = .007 at 5 years, P = .014 at 10 years, and P = .05 at 15
      years after transplantation. CONCLUSIONS: The increased level of PRA in kidney
      recipients is a risk factor increasing mortality after the transplantation.

PMID- 25380897
TI  - Influence of selected factors on long-term kidney graft survival--a multivariable
      analysis.
AB  - BACKGROUND: Long-term function of transplanted kidney is the factor determining
      quality of life for transplant recipients. The aim of this study was to evaluate
      the effect of selected factors on time of graft function after renal
      transplantation within 15 years of observation. METHODS: Preoperative and
      intraoperative factors were analyzed in 232 kidney recipients within a 15-year
      observation period. Analysis included age, sex, cause of recipient's renal
      failure, length of hemodialyses before transplantation, peak panel reactive
      antibodies test, human leukocyte antigen compatibility, cold ischemia time,
      delayed graft function occurrence, length and time of hemodialyses after
      transplantation, early graft rejection, creatinine level at days 1, 3, 7, 30, 90,
      and 180 after transplantation, and influence of these factors on the time of
      graft function. Statistical analysis was performed with the use of univariate and
      multivariate Kaplan-Meier test and Cox regression proportional hazards model,
      with P < .05 considered to be significant. RESULTS: Univariate analysis showed
      significantly shorter renal graft function in the group of recipients with higher
      creatinine levels in all of the analyzed time periods and in patients
      experiencing delayed graft function. Length of time of hemodialyses after
      transplantation and number of dialyses had significant impact on worsening of
      late transplant results. Multivariate analysis reported that early graft
      rejection in the postoperative period is an independent factor improving late
      graft function: P = .002; hazard ratio (HR), 0.49 (95% confidence interval [CI],
      0.31-0.78). Higher creatinine level at day 90 after kidney transplantation is a
      predictive factor of late graft dysfunction: P = .002; HR, 1.68 (95% CI 1.2
      2.35). CONCLUSIONS: Creatinine level at day 90 after renal transplantation is the
      prognostic factor of long-term kidney function. Early transplant rejection leads
      to introduction of more aggressive immunosuppression protocol, which improves
      long-term transplant results.

PMID- 25380899
TI  - Evaluation of selected markers of the immune system in children of renal
      transplant recipients.
AB  - OBJECTIVE: The aim of this study was to evaluate whether chronic use of
      immunosuppressive drugs during pregnancy in women after renal transplantation
      affects the concentration of immunoglobulin G (IgG) and IgM in the serum of their
      children. MATERIAL: Seventy-eight children aged 1 day to 15 years were enrolled.
      The study group consisted of 39 children born to renal transplant recipient
      mothers. The control group comprised 39 children whose mothers had not received
      immunosuppressive medications during pregnancy and were born at similar
      gestational age. METHODS: Serum concentrations of IgG and IgM were evaluated with
      the use of agglutination immunoassays on Siemens or Cobas device. Age-adjusted
      reference values for immunoglobulins formulated by Wolska-Kusnierz et al were
      used. Statistical analysis was performed with the use of Statistica 10.0 software
      with P value <.05 considered significant. RESULTS: Normal IgG concentrations were
      found in 82.05% (32) of children from the study group and 79.49% (31) of the
      control group. IgG concentrations below normal range were observed in 12.82% (5)
      of children from the study group and in 15.38% (6) of the control group. Normal
      concentrations of IgM were found in 53.85% (21) of children from the study group
      and in 61.54% (24) of the control group. Decreased levels of IgM were observed in
      38.46% (15) of children from the study group and 35.9% (14) of the control group.
      There were no significant differences regarding the analyzed values between the
      groups. CONCLUSION: The exposure to chronic intrauterine immunosuppression had no
      significant effect on the concentration of IgG or IgM in children born to kidney
      transplant recipients.

PMID- 25380900
TI  - Dynamics of changes in heart conduction system in dialyzed young adults after
      kidney transplantation--pilot study.
AB  - BACKGROUND: Cardiovascular complications are the main clinical problem in
      patients with end-stage renal failure (ESRF). After successful kidney
      transplantation, this situation improves, although cardiovascular complications
      remain a risk factor for increased mortality in these patients; therefore, their
      early identification is of key therapeutic and prognostic significance. This
      study was designed to determine a dynamics of changes in the heart conduction
      system in hemodialyzed young adult patients after kidney transplantation in a
      long-term follow-up, based on the body surface potential mapping (BSPM) method.
      METHODS: The study comprised 5 patients (mean age, 20.8 +/- 1.16 years) after
      kidney transplantation (KT) who had been chronically dialyzed before. The mean
      observation period was 6.7 +/- 1.71 years. All of the patients were submitted to
      the following examinations before and after KT: 12-lead electrocardiography
      (ECG), echocardiography, standard biochemistry, and BSPM (isochronous maps). The
      mean creatinine concentration was 1.38 +/- 0.05 mg/dL. The control group
      comprised 30 healthy persons. RESULTS: BSPM maps taken from the dialyzed patients
      demonstrated disturbed spreading of electric impulses within the heart ventricles
      in a type of left bundle branch block, despite normal 12-lead ECG and
      echocardiography results. A relationship was demonstrated between the BSPM
      changes and dialysis duration. After KT, the abnormal distribution of isochrones
      and ventricular activation times (VAT) presented some significant and specific
      regression. CONCLUSIONS: 1) In dialyzed patients, BSPM is a more sensitive method
      than ECG and enables early identification of changes in the heart conduction
      system presented as left bundle branch block. 2) Dialysotherapy duration before
      and after KT determines the extent of the BSPM changes. 3) Successful effects of
      KT bring about regression of intraventricular conduction disorders. 4) The
      observations need verification in a larger patient group.

PMID- 25380902
TI  - Left ventricular hypertrophy in renal transplant recipients in the first year
      after transplantation.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is a significant risk factor for
      cardiovascular complications in renal transplant recipients. The study objective
      here was to assess LVH and related factors in renal transplant recipients in the
      1st year after transplantation. METHODS: Echocardiographic examinations were
      performed in the early post-transplantation period in 43 patients (age, 43.9 +/-
      12.4 years; male, 53.5%) and at 1 year after transplantation in 40 patients. At
      the same time, basic blood tests, N-terminal pro-B-type natriuretic peptide (NT
      proBNP) level tests, and ambulatory blood pressure measurements were performed.
      LVH was diagnosed when LV mass index was >95 g/m(2) in women and >115 g/m(2) in
      men. Statistical analyses were performed with the use of the R Package. RESULTS:
      LVH (mainly concentric) was found in 51.2% of the patients in the early period
      and in 50% of the patients at 1 year. In 30% of the patients with baseline LVH it
      regressed at 1 year and in another 30% LVH developed de novo. In the early
      period, LV mass was influenced by age, sex, body mass index (BMI), estimated
      glomerular filtration rate (eGFR), and a history of cardiovascular disorders
      during dialysis therapy, whereas at 1 year after transplantation it was
      influenced by age, sex, BMI, 24-hour systolic blood pressure, a history of
      hypertension during dialysis therapy, and abnormal 24-hour blood pressure
      profile. Weight gain interfered with LVH regression during the 1st year after
      transplantation, whereas no improvement in blood pressure control contributed to
      de novo development of LVH. All other patients (those without LVH) had a
      morphologic abnormality of the left ventricle, the so-called concentric
      remodeling. Higher NT-proBNP levels were observed in patients with LVH.
      CONCLUSIONS: LVH is present in one-half of renal transplant recipients in the 1st
      year after transplantation, and concentric remodeling is present in the remaining
      patients of this group. An echocardiographic examination is indicated in every
      renal transplant recipient. Measurements of NT-proBNP levels are helpful in LVH
      diagnostics.

PMID- 25380903
TI  - Assessment of cardiovascular risk during peritransplant period in renal
      transplant recipients.
AB  - BACKGROUND: Cardiovascular (CV) diseases are the leading cause of death among
      patients with chronic kidney disease, including patients on dialysis and after
      kidney transplantation. The aim of study was the retrospective assessment of CV
      risk in renal transplant recipients during the peritransplant period. MATERIAL
      AND METHODS: Evaluation of CV risk was made using the Revised Cardiac Risk Index
      (RCRI). One hundred kidney transplant recipient (60 males/40 females)
      participated in the study. In 82 recipients (82%), the RCRI index was 2 points,
      which was associated with a 6.6% risk of cardiac events. The remaining 18
      patients (18%) had >=3 RCRI points, which was associated with an 11% risk. The
      median RCRI score in the study group was 2.26, which was related to a risk of
      7.39%. RESULTS: In the perioperative period, there were no CV events. The study
      group was observed for 5 years after transplantation, and during this time, 11 CV
      incidents occurred. Most of CV incidents occurred during the first 25 months
      after transplantation. Among patients, who underwent a CV incident, the RCRI was
      3 and 2 points in 4 and 5 patients, respectively. Significant correlations were
      found between RCRI and both age and time spent on dialysis (P < .001).
      CONCLUSIONS: Patients who qualify for a transplant are at a significant risk of
      having a CV incident in the peri- and postoperative periods. CV incidents did not
      occur in the perioperative period, although as many as 6% of patients experienced
      CV incidents within 2 years after transplant. Four (44%) of the 9 patients who
      experienced CV incidents after transplantation had a very high RCRI. This
      indicates the need for a very thorough long-term cardiologic supervision of
      transplanted patients.

PMID- 25380901
TI  - Open prospective study to evaluate cardiovascular risk factors and renal function
      in 2 dosage regimens of tacrolimus combined with mycophenolate mofetil and
      steroids in renal transplant patients: 5-year results.
AB  - BACKGROUND: Cyclosporine and tacrolimus (TAC) are the most potent
      immunosuppressants. TAC is considered less nephrotoxic, but may be an important
      factor in chronic graft dysfunction. The aim of the study was to evaluate kidney
      function and cardiovascular risk profile in 2 groups of low immunological risk
      kidney allograft recipients receiving 2 TAC dosages. MATERIALS AND METHODS:
      Patients were randomly assigned to 2 TAC-based treatments (group I [n = 14],
      standard dose; group II [n = 15], reduced dose). Patient and graft survival,
      graft function, occurrence of cardiovascular events (cardiac death, myocardial
      infarction, stroke), incidence of new-onset diabetes mellitus after
      transplantation, and cardiovascular risk factors were assessed over a 5-year
      period. RESULTS: Patient demographics and transplant characteristics were not
      statistically different between groups. TAC trough levels were significantly
      higher in group I for 24 months post transplant. Patient survival did not differ,
      but there were more acute rejection episodes and graft losses in group II. There
      were no significant differences in the rate of cardiac events. Graft function
      measured as serum creatinine levels and calculated glomerular filtration rate did
      not differ between groups. The same applies to new-onset diabetes mellitus after
      transplantation incidence. Office blood pressures were numerically higher in
      group I up to 24 months but this difference did not reach significance at any
      time. Similar results were obtained for serum lipids. CONCLUSIONS:
      Immunosuppression based on low doses of tacrolimus seems to be safe in the group
      of low immunological risk patients but in the 60-month follow-up does not offer
      any clear benefits in terms of potential nephrotoxicity or cardiovascular risk.

PMID- 25380904
TI  - N-terminal pro-B-type natriuretic peptide (NT-proBNP) assessment in the first
      year after renal transplantation and its relationship with graft function and
      left ventricular hypertrophy.
AB  - BACKGROUND: NT-proBNP is a natriuretic neurohormone released mainly from
      ventricular cardiomyocytes in conditions of volumetric or pressure overload; it
      is suitable for use as a marker of left ventricular hypertrophy (LVH), a common
      disorder in renal transplant recipients. The study objective here was to assess
      NT-proBNP levels in the 1st year after renal transplantation (RT) and its
      relationship with graft function and LVH. METHODS: Sixty patients (age, 49 +/-
      16.9 y; male, 58%) were subjected to prospective 1-year follow-up. Basic blood
      tests and NT-proBNP level measurements were performed twice (in the early period
      and at 1 year after transplantation). Cardiac echography was performed in 40
      patients. LVH was diagnosed when left ventricular mass index was >95 g/m(2) in
      women and >115 g/m(2) in men. Statistical analyses were performed with the use of
      the R Package. RESULTS: At 1 year after RT, the NT-proBNP level decreased >2-fold
      compared with the early period (median 171 pg/mL [interquartile range (IQR),
      104.5-283] vs 368 pg/mL[IQR, 170-629]; P = .00008). In the early post
      transplantation period, NT-proBNP correlated with the patient's age, body mass
      index, estimated glomerular filtration rate (eGFR), and left ventricular end
      diastolic dimension, and at 1 year after transplantation its correlation with the
      eGFR range (patients with eGFR >=60 mL min(-1) 1.73 m(-2) had significantly lower
      NT-proBNP levels than those with eGFR <60 mL min(-1) 1.73 m(-2)), with age,and
      with ejection fraction was found. Patients with LVH had higher NT-proBNP levels
      than those without LVH in the early period (median 511 pg/mL [IQR, 190-736] vs
      380 pg/mL [IQR, 217-511]; P = .09), and at 1 year (median 269 pg/mL [IQR, 155
      474] vs 133 pg/mL [IQR, 99-134]; P = .057). At NT-proBNP >480 pg/mL in the early
      period and >280 pg/mL at 1 year, LVH occurred with a 68% probability (P = .05 and
      P = .03, respectively). CONCLUSIONS: During the 1st year after RT, NT-proBNP
      levels decrease >=2-fold and are primarily related to eGFR. NT-proBNP
      measurements are useful in identifying patients with LVH.

PMID- 25380905
TI  - Bacterial and fungal infections in the early post-transplant period after kidney
      transplantation: etiological agents and their susceptibility.
AB  - BACKGROUND: Infections remain serious complications in solid-organ transplant
      recipients, despite professional medical care, the introduction of new
      immunosuppressive drugs, and treatment that decreases the risk of infections.
      METHODS: The study covered 295 adult patients undergoing kidney transplantation
      (KTx) between September 2001 and December 2007. All the patients were followed
      prospectively for infections from the KTx date and during the first 4 weeks after
      surgery. Samples of clinical materials were investigated for microbiological
      cultures. The microorganisms were cultured and identified in accordance with
      standard bacteriological procedures. Susceptibility testing was carried out
      through the use of Clinical and Laboratory Standards Institute procedures.
      RESULTS: From 295 KTx recipients, 1073 clinical samples were taken for
      microbiological examination. Positive cultures were 26.9% (n = 289) of all
      samples tested; 525 strains were collected. Gram-positive bacteria were isolated
      in 52.2% (n = 274), Gram-negative bacteria were isolated in 40.8% (n = 214), and
      fungal strains were isolated in 7% (n = 37). Urine specimens (n = 582) were
      obtained from 84.5% of 245 recipients during the first month after
      transplantation. Among the isolated bacterial strains (n = 291), the most common
      were Gram-negative bacteria (56.4%). Gram-positive bacteria comprised 35.7%;
      fungal strains were found in 23 cases (7.9%). In surgical site specimens (n =
      309), Gram-positive bacteria (72.1%) were the most common. Gram-negative bacteria
      comprised 24.4%. In blood specimens (n = 138), Gram-positive bacteria (81.6%)
      were the most common. Gram-negative bacteria comprised 15.8%; fungi were isolated
      in 2.6%. In respiratory tract specimens (n = 13), among the isolated bacterial
      strains (n = 8), the most common were Gram-positive bacteria (57.1%). Gram
      negative bacteria comprised 14.3%; fungi were isolated in 28.6%. CONCLUSIONS:
      Urine samples were predominantly positive after KTx. Our study showed Gram
      positive bacteria in 52.2% after kidney transplantation. The proportion of
      isolates of multi-drug-resistant bacterial strains (MRCNS, vancomycin-resistant
      strains, high-level aminoglycoside-resistant strains, extended-spectrum beta
      lactamase producers, and high-level aminoglycoside-resistant strains) was
      increased. These data indicate the need for strict adherence to infection control
      procedures in these patients.

PMID- 25380906
TI  - Superficial fungal infections in renal transplant recipients.
AB  - BACKGROUND: Renal transplant recipients (RTRs) are predisposed to fungal
      infections because of long-term graft-preserving immunosuppressive therapy.
      METHODS: We prospectively enrolled 223 consecutive adult RTRs. Patients were
      transplanted at 1 of 2 transplant centers in Poland. The group consisted of 97
      women (43%) and 126 men (57%). The control group consisted of 100 patients (39
      women and 61 men) randomly selected from the outpatient dermatology clinic and
      from hospital personnel. All RTRs and the control group were screened for the
      presence of superficial fungal infections. All patients were examined by the same
      dermatologist. The oral mucosa and the entire body surface were fully examined.
      Mucosal swabs were obtained from all patients in both the examined and control
      groups. Skin scrapings and swabs were obtained from any clinically suspicious
      lesions. Nail clippings were collected in the case of any nail changes. RESULTS:
      Superficial fungal infections have been detected in 133 RTRs (60%)and 27 controls
      (27%; P = .00001). One hundred eight RTRs (62%) developed superficial fungal
      infections in the first year after transplantation (P < .008). The most common
      site for superficial fungal infections in the RTRs group was the oral cavity.
      Candida albicans was the most frequently isolated species in the oral cavity.
      CONCLUSIONS: Superficial fungal infections in RTRs are statistically more common
      among RTRs than in the general population. Whether the drug was used separately
      or administrated under immunosuppressive combinations had no influence on the
      occurrence of fungal infections. The final results showed no correlation between
      patient age and the occurrence of fungal infections. Dermatologists who care for
      transplant patients should be aware of the clinical course of fungal species in
      RTRs compared with the general population.

PMID- 25380907
TI  - Acute graft pyelonephritis during the first year after renal transplantation.
AB  - INTRODUCTION: Urinary tract infections are the most common infections in renal
      transplant recipients. Acute graft pyelonephritis (AGPN) is considered a
      potential risk factor for poorer graft outcomes; however, its clinical impact
      still remains controversial. METHODS: This study analyzed urine cultures
      performed within the first 12 months after renal transplantation with reference
      to clinical data of patients who received a renal transplant at Gdansk
      Transplantation Centre between January 2007 and December 2009. Renal function
      assessed by creatinine concentration and estimated glomerular filtration rate was
      recorded 24 months after renal transplantation. RESULTS: This study examined
      urine cultures and clinical data from 209 renal transplant recipients, including
      59.3% men, with a mean age of 46 +/- 14 years. We observed 70 AGPN episodes
      defined as the presence of significant bacteriuria, fever >38 degrees , and/or
      graft pain and/or acute graft function impairment, including 13 cases of
      bacteremia, in 46 patients. This accounted for 22% of all diagnosed urinary tract
      infections. Over 80% of all AGPN episodes were diagnosed beginning from the
      second month posttransplantation, and the most frequently isolated uropathogen
      was Escherichia coli (65.7%, n = 46). Female sex, vesicoureteral reflux, or
      strictures at the ureterovesical junction and a history of cytomegalovirus
      infection emerged as independent predictors of AGPN. The evolution of renal graft
      function measured by serum creatinine concentration and MDRG eGFR rate did not
      differ significantly between patients with and without AGPN. CONCLUSIONS: AGPN
      may be a marker of an underlying impairment of urine flow, eg, due to
      vesicoureteral reflux or strictures at the ureterovesical junction, whereas it
      does not affect graft function in renal transplant recipients.

PMID- 25380908
TI  - Klebsiella spp urinary tract infections during first year after renal
      transplantation.
AB  - BACKGROUND: Urinary tract infections (UTIs) are the most common infections in
      renal transplant recipients (RTR). Klebsiella spp is a well-recognized source of
      nosocomial infections in immunocompromised patients and is also the most common
      pathogen capable of producing extended-spectrum beta-lactamases (ESBLs). METHODS:
      We performed a retrospective cohort study reviewing medical records of patients
      followed-up at Gdansk Transplantation Centre. We analyzed urine cultures
      performed within the first 12 months after renal transplantation (RT) with
      reference to clinical data. We recorded all Klebsiella spp UTIs. RESULTS: We
      studied urine cultures and clinical data from 335 RTRs. We observed 59 Klebsiella
      spp episodes in 24 RT patients, including 10 cases of acute graft pyelonephritis
      and 8 of urosepsis. More than half were caused by ESBL+, whereas there were no
      carbapenemase-producing strains. Almost 80% of episodes were diagnosed beginning
      from the second month post-transplantation. More than 60% of upper Klebsiella spp
      UTIs were due to ESBL+ strains, although we did not identify any host risk
      factors including vesico-ureteral reflux, strictures at the uretero-vesical
      junction, history of recurrent UTIs before RT, comorbidity measured by Charlson
      Comorbidity Index, history of acute rejection, use of induction, and type of
      immunosuppression used. Upper Klebsiella spp UTIs were slightly more prevalent in
      males with urinary flow impairment due to various reasons. CONCLUSIONS:
      Klebsiella spp virulence factors, not the host factors, seem to be mostly
      responsible for developing upper UTIs in RT patients.

PMID- 25380909
TI  - Impact of graft infection on long-term survival after kidney transplant.
AB  - BACKGROUND: Patients undergoing transplantation procedures are at a high risk of
      developing infections because of the need for immunosuppression. Infections
      presenting directly after renal transplantation greatly influence the overall
      success of the procedure. The aim of this study was to evaluate the influence of
      postoperative infection on the length of survival after renal transplant.
      METHODS: In 2009 a multicenter prospective trial evaluating the factors that
      influence the occurrence of postoperative infective complications was published
      by the authors. That study reported that 25 out of 232 recipients of a renal
      transplant were diagnosed with an infection. The present study shows the effect
      of postoperative infection on the length of survival after renal transplantation
      during a 15-year observation period. Statistical methods involved monofactorial
      and multifactorial Kaplan-Meier analysis for the length of survival and the Cox
      proportional hazards model for mortality prediction. A P value of <.05 was
      considered to indicate statistical significance. RESULTS: The analysis
      demonstrated that the lifespan of renal transplant recipients was decreased in
      those with postoperative infection, at both year 10 of the observation period (P
      = .013) and 15 years after transplantation (P = .012). Moreover, it was
      ascertained that an infection in the postoperative period was an independent risk
      factor increasing the mortality after renal transplantation: P = .026; hazard
      ratio 2.90 (95% confidence interval, 1.13-7.41). CONCLUSIONS: The occurrence of
      an infection in the postoperative period significantly decreases the lifespan of
      a renal transplantation recipient.

PMID- 25380910
TI  - Reliability of frozen section in the assessment of allograft steatosis in liver
      transplantation.
AB  - BACKGROUND: Because liver allograft steatosis is an important risk factor of
      graft dysfunction after liver transplantation, it must be taken into
      consideration during graft acceptance. The aim of this study was to evaluate the
      reliability of frozen section in the assessment of liver steatosis before
      transplantation. METHODS: The retrospective analysis was based on data of 112
      liver allograft procurements performed between 2003 and 2012. Hepatic steatosis
      was assessed in frozen and routine sections. Sensitivity, specificity, and
      positive and negative predictive values of the frozen section were evaluated with
      respect to detection of >30% and >50% steatosis. RESULTS: According to routine
      section assessment, there were 32 (28.6%) cases of steatosis >30% and 16 (14.3%)
      of >50%. The results of frozen section assessment were underestimated and
      overestimated in a similar low number of cases, both for the >30% (0.0% and 0.9%,
      respectively, P < 1.000) and the >50% (4.5% and 0.9%, respectively, P = .221)
      cutoff. Sensitivity, specificity, positive and negative predictive values of
      frozen section assessment were 100.0%, 98.8%, 97.0%, and 100.0%, respectively,
      for detection of >30% steatosis, and 68.8%, 99.0%, 91.7%, and 95.0%,
      respectively, for >50% steatosis. CONCLUSIONS: Considering high positive
      predictive value of frozen section assessment in detection of >50% steatosis, it
      may serve as a base to discard the use of graft for transplantation. However,
      according to the relatively moderate sensitivity of this method, decision of
      graft acceptance must also be made on consideration of other well-known factors
      for poor posttransplant function.

PMID- 25380911
TI  - The effects of in vitro hemodilution and fibrinogen concentrate substitution on
      thromboelastometry analysis in patients qualified for liver transplantation -
      preliminary results.
AB  - BACKGROUND: Dilutional coagulopathy might cause life-threatening hemorrhages in
      liver transplantation. Liver insufficiency is usually accompanied by alteration
      in fibrinogen (Fib) synthesis, which is one of the main clotting factors
      providing appropriate hemostasis. Intraoperative hemodilution results in further
      Fib concentration reduction enhancing coagulopathy and blood loss. Exogenous Fib
      substitution might prevent this. METHODS: A prospective study with a control
      group was designed. The study group consists of patients with cirrhosis who
      qualified for liver transplantation. Inclusion and exclusion criteria were
      strictly established. The blood collected from participants was diluted up to 30%
      and 60% with crystalloid (saline) or colloid (hydroxyethyl starch) in 2 parallel
      series. The first series consisted of diluted blood, the second of diluted blood
      with Fib concentrate. Thromboelastometry tests were performed on every blood
      sample. After collecting data from the first 12 participants, we performed a
      preliminary analysis. RESULTS: The maximum clot formation (MCF) in the EXTEM test
      decreased with progressive blood dilution in both study arms. The MCF values were
      lower than 35 mm in every diluted blood sample of the study group. The recovery
      of decreased MCF after Fib concentrate substitution was observed in both groups.
      The improvement in clot formation was also expressed as amplitude of clot
      firmness in the 10th minute (A10) in the FIBTEM test. CONCLUSIONS: Clot formation
      is disturbed more profoundly by hemodilution in cirrhotic patients. Fib
      concentrate substitution might be effective in the management of dilutional
      coagulopathy.

PMID- 25380912
TI  - Results of liver transplantation from old donors.
AB  - INTRODUCTION: Faced with a shortage of organs for liver transplantation, the use
      of grafts from older donors is justified. However, there remains little consensus
      on how this use impacts the graft and patient outcomes after transplantation from
      these older donors. The aim of the present analysis was to assess the graft and
      patient outcomes after liver transplantation from deceased donors >60 years of
      age. METHODS: From January 2007 to January 2011, 505 subjects were identified as
      liver graft donors after brain death, of which 7.35% were >=60. To determine the
      effect of donor age on graft and patient outcomes, we analyzed donor age,
      recipient age, the Model for End-State Liver Disease (MELD) score of recipients
      at the time of transplantation, early posttransplant complications, and
      mortality. RESULTS: The posttransplant follow-up was 29 +/- 25.5 months, and 3
      year patient mortality from donors, grouped according to age, was 7.92% with
      donors <30; 15.78% with donors 30-50, 10.68% with donors 50-60, and 12.50% with
      donors >60. After analysis of patient and graft survival based on donor graft
      age, 3-year patient survival according donor age was 89.29% with donors <30,
      83.85% with donors 30-50, 89.89% with donors 50-60, and 87.50% with donors >60.
      Analysis showed overall patient and graft survival rates from older donors were
      not worse than those from younger donors (P > .1). Among the cases, 3-year
      patient survival according to MELD score was 91.19% with a MELD of I, 85.37% with
      a MELD of II, and 67.67% with a MELD of III; differences in graft and patient
      survival when comparing low MELD I and high MELD III were significantly different
      (P < .01). CONCLUSIONS: A more advanced age of a donor should not be a
      contraindication for liver transplantation. The present analysis shows that liver
      grafts from donors >60 can be used safely in older recipients who presented with
      relatively low MELD scores. Analyses also indicate that high MELD obtained before
      transplantation may be an important prognostic factor for graft and patient
      survival.

PMID- 25380913
TI  - Outcomes following liver transplantation for metastatic neuroendocrine tumors.
AB  - INTRODUCTION: Metastatic disease is generally considered as an absolute
      contraindication for liver transplantation. However, due to relatively low
      aggressiveness and slow progression rates, liver metastases from neuroendocrine
      tumors (NETs) form an exception to this rule. Given the scarcity of available
      data, the purpose of this study was to evaluate long-term outcomes following
      liver transplantation for NET metastases. MATERIAL AND METHODS: There were 12
      primary liver transplantations in patients with NET metastases out of 1334 liver
      transplantations performed in the Department of General, Transplant and Liver
      Surgery (Medical University of Warsaw) in the period between December 1989 and
      October 2013. Overall survival (OS) and disease-free survival (DFS) were set as
      primary and secondary outcome measures, respectively. RESULTS: Median follow-up
      was 7.9 years. For all patients, OS rate was 78.6% at 10 years and DFS rate was
      15.5% at 9 years. Intraoperative transfusions of packed red blood cells (P =
      .021), Ki-67 proliferative index more than 2% (P = .048), and grade 2 tumors (P =
      .037) were identified as factors significantly associated with worse DFS.
      Notably, loss of E-cadherin expression (P = .444), mitotic rate (P = .771),
      extent of liver involvement (P = .548), primary tumor site (P = .983), and
      recipient age (P = .425) were not significantly associated with DFS. CONCLUSIONS:
      Excellent long-term OS rates support liver transplantation for unresectable NET
      metastases despite almost universal post-transplantation tumor recurrence.
      Selection of patients with G1 tumors with Ki-67 index not exceeding 2% and
      reducing the requirement for intraoperative blood transfusions might improve DFS
      rates.

PMID- 25380914
TI  - Relationship between pretransplantation liver status and health-related quality
      of life after grafting: a single-center prospective study.
AB  - BACKGROUND: Severity of liver disease evaluated with Model for End-Stage Liver
      Disease (MELD)/Child-Pugh-Turcotte (CPT) score is of importance in liver
      transplantation (LTx) assessment. The Medical Outcomes Study Short Form (SF-36)
      is a widely used generic questionnaire of health-related quality of life (HRQoL).
      This study was a prospective analysis of the effect of pretransplantation liver
      status on HRQoL after the procedure. MATERIALS AND METHODS: One hundred and seven
      (62 male, 45 female, median age 52 years) consecutive patients were included.
      MELD/CPT score and diabetes status were evaluated during LTx assessment. Patients
      were divided into 3 groups depending on the period after LTx: 6 to 12 months
      (group I), 13 to 36 months (group II), and >37 months (group III). They also were
      divided into 2 groups depending on the age at LTx: group I (<50 years) and group
      II (>50 years). SF-36 was used in the assessment of HRQoL. RESULTS: Correlation
      between pretransplantation MELD/CPT score and HRQoL was only seen in the general
      health domain of the SF-36 in patients from group I (r = 0.64; P = .004 and r =
      0.61; P = .02, respectively). Diabetes exerted a significant effect on the
      physical component summary (P = .02), again in group I. No significant
      correlation was observed between MELD/CPT score and the presence of diabetes in
      groups II and III. Regarding age at LTx, no significant correlation between
      MELD/CPT score and HRQoL was seen. CONCLUSIONS: Liver status assessed with MELD
      and CPT scores before transplantation has a minor effect on HRQoL after LTx and
      exerts no significant effect in patients evaluated >12 months after LTx. Patients
      with diabetes seem to have worse quality of life early after surgery; however,
      diabetic and nondiabetic patients had comparable HRQoL scores later on after LTx.

PMID- 25380915
TI  - Poor outcomes after liver transplantation in patients with incidental
      cholangiocarcinoma irrespective of tumor localization.
AB  - INTRODUCTION: After liver transplantation for cholangiocarcinoma (CCC), patients
      have a poor prognosis without use of specific therapeutic strategies.
      Accordingly, recipients with incidental CCC might have the highest risk of
      recurrent disease; however, sparse data on the long-term outcome of unselected
      patients with incidental CCC have been published. The aim of this study was to
      evaluate the post-transplantation outcomes of patients with incidental CCC with
      special focus on tumor localization. MATERIAL AND METHODS: There were 11 primary
      liver transplantations in patients with incidental CCC of 1310 liver
      transplantation procedures performed between December 1994 and August 2013. All
      patients with incidental CCC received a chemotherapy regiment including
      gemcitabine/5 fluorouracil, doxorubicin, and mitomycin. The patients were
      switched from calcineurin inhibitors to mammalian target of rapamycin inhibitor
      based immunosuppression shortly after CCC diagnosis. RESULTS: Intra- and
      extrahepatic tumors were found in 6 and 5 patients, respectively. At median
      follow-up examination of 26.3 months there were 8 CCC recurrences and 7 patient
      deaths. Overall survival after liver transplantation for incidental CCC was 88.9%
      at 1 year, 44.4% at 2 years, and 14.8% at 3 years. The corresponding rates of
      recurrence-free survival were 45.7%, 45.7%, and 0.0%, respectively. Post
      transplantation CCC recurrences were universal with 0% 3-year recurrence-free
      survival both in patients with intra- and extrahepatic tumors (P = .475).
      CONCLUSIONS: Incidental CCC in liver transplantation is associated with poor
      outcomes irrespective of tumor localization. Introduction of new adjuvant
      multimodal treatment concepts is necessary to improve the prognosis for this
      subgroup of patients.

PMID- 25380916
TI  - Bacterial and fungal infections in the early post-transplantation period after
      liver transplantation: etiologic agents and their susceptibility.
AB  - OBJECTIVE: It has been reported in many studies that one of the main factors
      influencing morbidity and mortality in patients receiving transplants is
      infection after transplantation. PATIENTS AND METHODS: The study included 190
      adult patients undergoing orthotopic liver transplantation (OLT) between
      September 2001 and December 2007. All the patients were followed prospectively
      for infections from the OLT date and during the first 4 weeks after surgery.
      Immunosuppression consisted of steroids and tacrolimus. Antimicrobial prophylaxis
      included piperacillin/tazobactam, fluconazole, and selective bowel
      decontamination (SBD) was performed. Samples of clinical materials were
      investigated for microbiological cultures. The micro-organisms were cultured and
      identified in accordance with standard bacteriological procedures. Susceptibility
      testing was performed using Clinical and Laboratory Standards Institute
      procedures. RESULTS: From 190 OLT recipients, 2213 clinical samples were obtained
      for microbiological examination. Positive cultures were found in 27.2% (n = 603)
      of all samples tested; 1252 strains were collected. Gram-positive bacteria were
      found in 64.1% (n = 802), Gram-negative bacteria were found in 31.6% (n = 396),
      and fungal strains were isolated in 4.3% (n = 54). Surgical site specimens (n =
      1031) were obtained from 190 recipients during the first month after
      transplantation. Positive cultures accounted for 29.2% (n = 301) of all samples
      tested. Among the isolated microbial strains (n = 677), most common were Gram
      positive bacteria (73.7%; n = 499). Gram-negative bacteria comprised 25.1% (n =
      170). There were fungal strains in 1.2% (n = 8). There were 539 urine specimens.
      Positive cultures accounted for 16.7% (n = 90) of those. Among the isolated
      microbial strains (n = 210), most common were Gram-negative bacteria (62.4%; n =
      131). Gram-positive bacteria comprised 28.6% (n = 60) and fungi 9% (n = 19).
      There were 549 blood specimens. Positive cultures were found in 30.6% (n = 168)
      of all samples tested. Among the isolated microbial strains (n = 263), most
      common were Gram-positive bacteria in 72.3% (n = 190); Gram-negative bacteria
      were found in 26.2% (n = 69), and fungal strains were isolated in 1.5% (n = 4).
      There were 69 respiratory tract specimens. Positive cultures were found in 46.4%
      (n = 32) of all samples tested. Among the isolated microbial strains (n = 84),
      most common were Gram-positive bacteria (51.2%; n = 43); Gram-negative bacteria
      comprised 27.4% (n = 23) and fungi 21.4% (n = 18). CONCLUSIONS: (1) Surgical site
      samples were predominated samples after LTx. (2) Our study showed Gram-positive
      bacteria were 64.1% (n = 802), Gram-negative bacteria, 31.6% (n = 396) and fungal
      strains isolated in 4.3% (n = 54). (3) The increased proportion of isolates of
      multi-drug-resistant bacterial strains (methicillin resistant coagulase negative
      Staphylococcus, vancomycin-resistant Enterococcus, high-level aminoglycoside
      resistance, and extended- spectrum beta-lactamase). (4) These data indicate
      strict cooperation infection control procedures in these patients.

PMID- 25380917
TI  - Is neutrophil gelatinase-associated lipocalin an optimal marker of renal function
      and injury in liver transplant recipients?
AB  - BACKGROUND: Recently, research has focused on the association of neutrophil
      gelatinase-associated lipocalin (NGAL) with acute and/or active kidney injury.
      However, it should be remembered that NGAL is involved in iron metabolism and
      antimicrobial defense mechanisms. METHODS: One hundred seven consecutive liver
      transplant recipients were included in this study. Plasma and urine NGAL levels
      were measured with the use of enzyme-linked immunosorbent assay. NGAL levels were
      studied as plasma concentrations (pNGAL), urine concentrations (uNGAL), urinary
      NGAL to creatinine ratio (uNGAL/Cr), and fractional NGAL secretion (fNGAL).
      RESULTS: pNGAL was found to be inversely correlated with estimated glomerular
      filtration rate (eGFR) and plasma cystatine C (pCysC) (r = -0.26 and P = .007, r
      = -0.38 and P = .00006, respectively). uNGAL was positively correlated with
      urinary cystatine C to creatinine ratio (uCysC/Cr) and fractional cystatine C
      excretion (fCysC) (r = 0.43 and P = .000004; r = 0.4 and P = .1; respectively).
      uNGAL/Cr was inversely correlated with hematocrit (Htc) and hemoglobin (Hb) (r = 
      0.35 and P = .0002; r = -0.39 and P = .00004; respectively), and positively
      correlated with uCysC/Cr (r = 0.5 and P < .0000001). fNGAL was directly
      correlated with uCysC/Cr and fCysC (r = 0.53 and P < .0000001; r = 0.39 and P =
      .00005; respectively) and inversely correlated with red blood cell count (RBC; r
      = -0.31 and P = .001). We observed significant differences of pNGAL, uNGAL/Cr,
      and fNGAL between sexes, with highest values of uNGAL, uNGAL/Cr, and fNGAL in
      women and pNGAL in men. In multivariate regression analysis, pNGAL was positively
      correlated with time elapsed from liver transplantation, neutrophil count, pCysC,
      and sex (beta = 0.36 and P = .00001; beta = 0.32 and P = .0001; beta = 0.58 and P
      < .0000001; beta = 0.17 and P = .025; respectively) and inversely correlated with
      patient's age (beta = -0.18 and P = .02) with R = 0.67 and R(2) = 0.45,
      independently from blood glucose, eGFR, RBC, white blood cell count, Hb, uCysC,
      uCysC/Cr, and fCysC. CONCLUSIONS: Plasma and urine NGAL levels are strongly
      correlated not only with kidney function parameters, but also with red and white
      blood cell parameters and patient's age and sex.

PMID- 25380918
TI  - Risk factors of acute renal failure after orthotopic liver transplantation:
      single-center experience.
AB  - BACKGROUND: Acute renal failure (ARF) is one of the most significant
      complications of orthotopic liver transplantation (OLT), associated with
      increased mortality rate and the development of chronic renal dysfunction. The
      aim of the study was to determine the perioperative risk factors for ARF in
      patients without previous history of renal disease who are undergoing OLT.
      MATERIALS AND METHODS: Forty-six patients who developed ARF after OLT performed
      in 1 transplant center were included in the study, and 52 consecutive patients
      without that complication served as a control group. Renal dysfunction was
      defined as a glomerular filtration rate <60 mL/min/1.73 m(2). The data concerning
      preoperative diseases, perioperative renal function, first-line immunosuppressive
      therapy, and blood transfusion requirement were retrospectively analyzed and
      compared among groups. Logistic regression modeling was used to determine risk
      factors for ARF. RESULTS: Patients who developed ARF were significantly older
      (mean age 53.3 vs 46.3 years, P = .057), had higher level of preoperative (0.79
      vs 0.71 mg/dL, P = .0062) and intraoperative (0.85 vs 0.74 mg/dL, P = .0045)
      creatinine. The risk factors for ARF were intraoperative and 24-hour post
      transplant creatinine level >0.9 mg/dL and high-dose tacrolimus-based
      immunosuppression. Transfusion of <=6 units of red blood cells diminished the
      risk of ARF. Sex and preoperative diseases were not predictive to ARF in our
      regression models. CONCLUSION: Careful operative technique with low blood loss
      and immunosuppressive therapy of low nephrotoxic potential should be recommended
      in older patients to diminish the risk of renal dysfunction after orthotopic
      liver transplantation. Patients with higher levels of perioperative creatinine
      should be considered to have first-line immunosuppression without calcineurin
      inhibitors or with low-dose immunosuppressants of known nephrotoxic potential.

PMID- 25380919
TI  - Analysis of the selected biochemical parameters of liver and kidney function in
      children of mothers after liver transplantation.
AB  - INTRODUCTION: Children of mothers after liver transplantation (LT) are exposed
      during fetal life to the immunosuppressive agents. These drugs may have
      hepatotoxic and nephrotoxic effects. OBJECTIVES: The aim of the work was to
      assess liver and kidney parameters of children born from mothers who had LT.
      MATERIALS AND METHODS: The research included 51 children of mothers after LT and
      51 children from a control group who were born in the First Department of
      Obstetrics and Gynecology in Warsaw between 2001 and 2013. The control group
      consisted of children born in the similar gestational age. Analysis concerned
      neonates, infants, and children older than 12 months. Two liver parameters
      (alanine transaminase [ALT] and aspartate transaminase [AST]) as well as two
      kidney parameters (urea and creatinine) were assessed. For statistical analysis
      we used Fisher's exact test and the Mann-Whitney test. RESULTS: All children from
      the LT group had correct ALT levels. In the control group, 5 of 51 cases (9.8 %)
      had levels that were greater than the norm, and those cases concerned only
      children younger than 12 months. The average concentration of ALT in the LT group
      was 15.14 U/L and the average for the control group was 22.6 U/L (P = .012699,
      Mann-Whitney test). Three of 51 children in the LT group (5.9%) and 8 of 51
      (15.7%) in the control group had AST levels that were increased (P = .2003;
      Fisher's exact test). Incorrect AST levels were reported in all age groups.
      Incorrect values of kidney parameters concerned only neonates. Increased
      creatinine levels were reported in 3 of 51 cases (5.9%) in the LT group and in 1
      of 51 cases (1.96%) in the control group (P = .6175; Fisher's exact test). The
      average concentration of creatinine in children of mothers after LT was 0.51
      mg/dL, and the average of the control group was 0.44 mg/dL (P = .223698; Mann
      Whitney test). Only 1 of 51 children in the LT group (1.96%) had an increased
      urea level. All children from both the LT and the control groups had normal
      ultrasound images of urinary tract and liver. CONCLUSION: Exposure to
      immunosuppressive drugs during fetal life does not result in the occurrence of
      serious disturbances of liver function and kidneys function in children of
      mothers after LT.

PMID- 25380920
TI  - Intrauterine growth restriction in pregnant renal and liver transplant
      recipients: risk factors assessment.
AB  - BACKGROUND: Nowadays pregnancy after organ transplantation is possible due to
      advances in surgical and immunosuppressive therapies. One of the possible
      complications in pregnancy after organ transplantation is intrauterine growth
      restriction (IUGR). This may lead to various adverse perinatal outcomes.
      Prevalence of IUGR in the general population is estimated at 3%-10% with smoking
      being the most frequent maternal risk factor. The aim of this study was to
      determine the risk factors of IUGR in pregnant renal transplant recipients (RTR)
      or liver transplant recipients (LTR) in comparison with healthy pregnant women.
      METHODS: Retrospective analysis included 48 RTR and 52 LTR. IUGR was defined as
      estimated fetal weight less than the 10th percentile for gestational age. IUGR
      was diagnosed in 15 (31.3%) pregnant RTR and in 10 (19.2%) LTR. The control group
      consisted of 60 healthy pregnant women diagnosed with IUGR. Fisher exact test and
      Student t test were used to assess the differences in fractions and means,
      respectively, between distinguished groups of patients. Test for fractions based
      on asymptotic normal distribution was used to compare the proportion of patients
      with IUGR with the proportion of 10% in the general population. The logistic
      regression model was used to assess the statistical significance of correlations
      between the assumed risk factors and the prevalence of IUGR in multivariate
      settings. RESULTS: Hypertension, anemia, and proteinuria were the most frequent
      complications in the study group. They were more prominent in RTR than in LTR.
      Hypertension was diagnosed in all RTR, whereas severe anemia requiring
      erythropoietin treatment or blood transfusion was found in 4 RTR and in 1 LTR.
      CONCLUSION: IUGR is more common in organ recipients. Therefore, vigilant
      obstetric care is highly recommended in pregnant patients after renal or liver
      transplantation. Hypertension, severe anemia, and proteinuria proved not to be
      statistically significantly correlated with the prevalence of IUGR among patients
      after transplantation.

PMID- 25380921
TI  - Neurological development of children born to liver transplant recipients.
AB  - INTRODUCTION: Immunosuppressive treatment used in pregnant liver recipients may
      have a negative impact on fetal development and successively a child. AIM: The
      aim of the study was to make a neurological assessment of infants and children
      born to liver transplant recipients (LTRs) born between December 4, 2001, and
      February 11, 2013, in the 1(st) Department of Obstetrics and Gynecology, Medical
      University of Warsaw. METHODS AND MATERIALS: The study involved 88 children, of
      whom 44 children were born to LTR mothers, and 44 children born to women who were
      not organ recipients and delivered at a similar gestational age. The gestational
      age of neonates ranged from 33 to 41 weeks, and the birth weight ranged from 1420
      g to 4100 g. The neurological examination was performed in children from 7 weeks
      to 10 years of age. The neurological development was assessed by a specialist in
      pediatric neurology. The results of the examination were divided according to the
      following criteria: 1) normal development, 2) slight disorders, 3) moderate
      disorders, and 4) severe disorders. The Fisher's exact test was used for
      statistical analysis. RESULTS: Normal development was found in 35 of 44 (79.54%)
      children in the LTR group and 39 of 44 (88.63%) children in the control group (P
      = .3827). Slight disorders were observed in 6 of 44 (13.63%) children in LTR
      group and 5 of 44 (11.36%) children in the control group. Moderate disorders were
      found only in 3 of 44 (6.81%) children in the LTR group. No severe disorders were
      observed in both groups. CONCLUSIONS: Neurological development of children born
      to the liver recipients who were exposed to chronic immunosuppressive treatment
      in their fetal lives is the same as that of children whose mothers have not
      undergone organ transplantation.

PMID- 25380922
TI  - Bacterial and fungal infections in the early post-transplantation period after
      simultaneous pancreas-kidney transplantation: etiological agents and their
      susceptibility.
AB  - OBJECTIVE: This study aims to evaluate the frequency of microbial isolates and
      their susceptibility profiles cultured from clinical samples obtained from 26
      simultaneous pancreas-kidney transplant (SPK) recipients suspected of infections
      during the early post-transplantation period. PATIENTS AND METHODS: Data on
      microbiologic culture of 26 adult patients undergoing SPK were collected
      prospectively from 2001 to the end of 2006. Isolation and identification of
      cultured micro-organisms were performed according to standard microbiological
      procedures and commercially available tests. Susceptibility of the strains to
      antibacterial agents was made by the Clinical and Laboratory Standards Institute
      guidelines. RESULTS: All the patients were followed prospectively for the first 4
      weeks after surgery. In total, 263 samples from clinical materials obtained from
      26 SPK recipients were cultured. Bacterial cultures were positive in 29.3% (n =
      77) clinical samples. Of these, 219 microbial strains were cultured. Gram
      positive bacteria were found in 64% (n = 140), Gram-negative bacteria in 22.8% (n
      = 50), and fungal strains were isolated in 13.2% (n = 29). Incidence rate values
      for subsequent isolation of micro-organisms in the sub-periods of time for
      decreasing the SPK were Gram-positive bacteria (102.3-18.7; I versus IV), growing
      the Gram-negative bacteria (14-46.1 I versus III) IV were 14, decreasing to fungi
      (22.1-1.6, I versus IV). Until now this early post-transplantation period was
      considered homogeneous time after transplantation. This study shows that this
      period is actually heterogenous, with statistically significant differences being
      observed between results obtained in consecutive 4 weeks after transplantation.
      CONCLUSIONS: The results of this study show that the incidence rate was elevated
      with increasing age in the SPK group of patients. In the SPK group, our data
      showed the highest rate of isolation of micro-organisms compared with recipients
      of kidneys or liver.

PMID- 25380923
TI  - Multivariate analysis of complications after simultaneous pancreas and kidney
      transplantation.
AB  - OBJECTIVE: Identification of factors that have an impact on postoperative
      complications after simultaneous pancreas and kidney transplantation (SPKTx)
      could help overcome limitations of this kind of treatment. METHODS: Postoperative
      complications among 112 SPKTx recipients were divided into 3 groups: related to
      transplanted pancreas (n = 66), related to transplanted kidney (n = 23) and
      general surgical complications (n = 31) 120 refers to complications among 112
      recipients. According to the modified Clavien-Dindo scale, complications were
      classified according to their severity for each group. Risk factors for
      complication development related to donor, recipient, surgical technique, and
      immunosuppression were included to establish the multivariable model using
      logistic regression. RESULTS: Multiple regression analysis showed the following
      independent factors influenced mortal complications due to transplanted pancreas:
      age of donor (OR, 1.07; P < .04), duration of vascular pancreas anastomosis above
      35 minutes (OR, 3.94; P < .04) and duration of recipient dialysis above 24 months
      before transplantation (OR, 0.14; P < .01). Area under receiver operating
      characteristic curve for this model was 0.8. CONCLUSION: To improve results, the
      following modification of identified risk factors should be assumed: selection of
      donor in term of age, shortening of the second warm ischemia time, and adjustment
      of the waiting list to avoid prolongation of recipient dialysis before SPKTx.

PMID- 25380924
TI  - Quality of pancreatic transplant program assessment using a risk-adjusted
      cumulative sum chart: experience from a single, small center.
AB  - BACKGROUND: The high rate of complication after pancreas transplantation not only
      had an impact on recipient quality of life and survival but also had significant
      financial implications. Thus, monitoring transplant center performance was
      crucial to indentifying changes in clinical practice that result in quality
      deterioration. OBJECTIVE: To evaluate retrospectively the quality of the single,
      small pancreatic transplant program and to establish prospective monitoring of
      the center using risk-adjusted cumulative sum (CUSUM). METHODOLOGY: From 1988 to
      2014, 119 simultaneous pancreas and the kidney transplantations (SPKTx) were
      performed. The program was divided into 3 eras, based on surgical technique and
      immunosuppression. Analyses of the 15 fatal outcomes due to complication from
      pancreatic graft were performed. The risk model was developed using multivariable
      logistic regression analysis based on retrospective data of 112 SPKTx recipients.
      The risk-adjusted 1-sided CUSUM chart was plotted for retrospective and
      prospective events. The upper control limit was set to 2. RESULTS: There were 2
      main causes of death: multiorgan failure (73.3%; 11/15) and septic hemorrhage
      (26.7%; 4/15). Quality analysis using the CUSUM chart revealed that the process
      was not homogeneous; however, no significant signal of program deterioration was
      obtained and the performance of the whole program was within the settled control
      limit. CONCLUSION: For a single pancreatic transplant center. The risk-adjusted
      CUSUM chart was a useful tool for quality program assessment. It could support
      decision making during traditional surgical morbidity and mortality conferences.
      For small transplant centers, increasing the sensitivity of the CUSUM method by
      lowering the upper control limit should be considered. However, an individual
      assessment approach of the for particular centers is recommended.

PMID- 25380925
TI  - Early complications related to the transplanted kidney after simultaneous
      pancreas and kidney transplantation.
AB  - OBJECTIVE: Simultaneous pancreas and kidney transplantation (SPKTx) is the most
      often performed multiorgan transplantation. The main source of complication is
      transplanted pancreas; as a result, early complications related to kidney
      transplant are rarely assessed. The aim of this study was to evaluate prevalence,
      types, and severity of postoperative complications due to kidney graft among the
      simultaneous pancreas and kidney recipients. METHODS: Complications related to
      transplanted kidney among 112 SPKTx recipients were analyzed. The indication for
      SPKTx was end-stage diabetic nephropathy due to long-lasting diabetes type 1. The
      cumulative survival rates for kidney graft function and cumulative freedom from
      complication on days 60 and 90 after transplantation were assessed. Severity of
      complications was classified according to the modified Dindo-Clavien scale.
      RESULTS: The 12-month cumulative survival rate for kidney graft was 0.91.
      Cumulative freedom from complication on the 60th day after transplantation was
      0.84. The rates for II, IIIA, IIIB, IVA, and IVB severity grades were: 34.9%,
      4.3%, 26.1%, 26.1%, and 8.6%, respectively. Acute tubular necrosis and rejection
      were the most frequent (43.4%) cause of complication. The most frequent reasons
      for graft nephrectomy were infections (2/7; 28.6%) and vascular thrombosis due to
      atherosclerosis of recipient iliac arteries (2/7; 28.6%). The most severe (IVB)
      complications were caused by fungal infection. CONCLUSION: Rate and severity of
      complications due to renal graft after SPKTx was low; however, to prevent the
      most serious ones reduction of fungal infection was necessary.

PMID- 25380926
TI  - Surgical complications related to transplanted pancreas after simultaneous
      pancreas and kidney transplantation.
AB  - OBJECTIVE: Simultaneous pancreas and kidney transplantation (SPTKx) is
      characterized by the high rate and variability of postoperative complications,
      which could be a limitation of this treatment. The aim of this study was to
      evaluate prevalence, types, and severity of postoperative complications due to
      pancreas graft among the simultaneous pancreas and kidney recipients. METHODS:
      Postoperative complications related to transplanted pancreas among 112 SPTKx
      recipients were analyzed. The cumulative survival rates for pancreas graft
      function and cumulative freedom from complication on day 60 after transplantation
      were assessed. Severity of complications was classified according to a modified
      Clavien-Dindo scale. RESULTS: The 12-month cumulative survival rate for
      pancreatic graft was 0.74. Cumulative freedom from complication on the 60th day
      after transplantation was 0.57. The rates for II, IIIA, IIIB, IVA, and IVB
      severity grades were 10,6%, 4,5%, 19,7%, 44%, and 21,2%, respectively. The most
      severe (IVB) transplanted pancreas complications were due to graft inflammation,
      infection, pancreatic abscess, and local or diffuse necrosis. The most frequent
      reason for graft pancreatectomy was vascular thrombosis 35.9% (14/39). The
      mortality rate after graft pancreatectomy was significantly lower for vascular
      thrombosis than for infection (0/14 vs 11/25; P < .05). CONCLUSION: Reducing
      vascular thrombosis could preserve graft function rate. Preventing graft
      inflammation and infection would reduce mortality.

PMID- 25380927
TI  - Role of 16-multidetector computerized tomography in evaluation of graft failure
      risk in patients with pancreatic graft thrombosis after simultaneous pancreas and
      kidney transplantation.
AB  - BACKGROUND: Thrombosis of the pancreatic graft vessels is a common complication
      in patients after pancreas transplantation. The aim of this study was to evaluate
      the usefulness of 16-multidetector computerized tomography (16-MDCT) with volume
      rendering (VR) and maximum intensity projection (MIP) reconstruction as a
      predicting method of pancreatic graft loss after simultaneous pancreas and kidney
      transplantation. METHODS: Within 6-8 days after combined kidney-pancreas
      transplantation, MDCT was performed in 60 patients. Secondary reconstructions
      were obtained with the application of VR and MIP algorithms. Vessel anastomosis,
      extra- and intrapancreatic arteries, venous morphology, and enhancement of
      graft's parenchyma were evaluated. The stenosis grade of pancreatic graft vessels
      and the areas of graft parenchyma malperfusion were evaluated. RESULTS:
      Thrombosis of pancreatic graft vessels was recognized in 26 patients (43%),
      however only one-half of them required graftectomy. There were 17 cases of large
      vessel thrombosis and 9 cases of small intragraft vessel thrombosis. In 13
      (86.6%) out of 15 recipients parenchymal malperfusion resulted in graft lost. It
      appeared that vessel narrowing >40% was a threshold for pancreatic graft loss
      with sensitivity and false positive values of 100% and 9%, respectively. For
      parenchyma nonenhancement >60% the sensitivity and false positive values of 100%
      and 0% were significantly associated with pancreatic graft loss (P < .0001).
      CONCLUSIONS: Vascular occlusion of >40% and necrosis >60% of parenchymal volume
      correspond with pancreatic graft loss.

PMID- 25380928
TI  - Effect of immunosuppressive therapy on the serum fatty acids of phospholipids
      fraction in patients after heart transplantation.
AB  - BACKGROUND: The effects of tacrolimus (Tac) and cyclosporine (CsA) on lipid
      profile is well known; however, little is known about the changes in fatty acids
      (FA) of phosholipids fraction (PL) in heart transplant patients after treatment
      with these immunosuppressants. This study aimed to investigate the effect of Tac
      and CsA on serum FA of PL in heart transplant patients. METHODS: The study
      included 23 patients after heart transplantation on Tac (n = 14; group II) or CsA
      (n = 9; group I). Eleven healthy persons served as a control group. Serum FA of
      PL were extracted, separated on Sep-Pak NH2, methylated, and measured with the
      use of gas chromatography. Chemstation software was used to analyze the data.
      RESULTS: No differences between the studied groups and control were noted for
      saturated FA, monounsaturated FA, polyunsaturated FA (PUFA), total FA, and PUFA n
      6. The mean value of PUFA n-3 was significantly higher in the CsA group compared
      with the Tac group (P < .015) and control (P < .002) as well as in the Tac group
      compared with control (P < .001). For individual FA, higher mean concentration,
      compared with control, was found for C24, C20:2, C20:4, and C22:6 (P < .001 in
      all cases) and lower for C18:2cis (P < .001 in both groups) and for C18:3 in the
      Tac group. The mean values of PUFA n-6 to PUFA n-3 ratios were lower than in
      control (both P < .001). CONCLUSIONS: Different pattern of FA of PL may indicate
      the different FA metabolism in heart transplant patients treated by different
      immunosuppressants. This should be taken into account when FA supplementation in
      these patients is considered.

PMID- 25380929
TI  - Inadequate blood pressure control in orthotopic heart transplant: is there a role
      of kidney function and immunosuppressive regimen?
AB  - INTRODUCTION: Cardiac transplantation is the definitive therapy for eligible
      patients with end-stage heart failure. Hypertension is a widely accepted risk
      factor for its outcome. PATIENTS AND METHODS: We analyzed 169 heart transplant
      recipients. The diagnosis of hypertension was made on the basis of information
      gathered at 3 consecutive visits. Complete blood count, urea, serum lipids,
      fasting glucose, creatinine, and N-terminal pro-B-type natriuretic peptide were
      also studied. RESULTS: In the orthotopic heart transplantation (OHT) population,
      11% had diabetes and 68% had chronic kidney disease. Hypertension was diagnosed
      and treated in 68% of the OHT patients. Hypertensive patients were significantly
      older, with a lower estimated glomerular filtration rate and higher serum
      creatinine and erythrocyte count. Thirty-three percent of patients did not
      achieve target blood pressure despite optimal medical treatment. Patients treated
      with tacrolimus had similar systolic blood pressure compared with those treated
      with cyclosporine (with a tendency to have lower values). Patients treated with
      mammalian target of rapamycin inhibitors had similar systolic and diastolic blood
      pressures compared with those treated without these inhibitors. In the group of
      patients given steroids, systolic and diastolic blood pressures were
      significantly lower than in the group not treated with steroids. In addition,
      steroid-treated patients had a significantly lower estimated glomerular
      filtration rate, hemoglobin, and erythrocyte count and higher serum creatinine, N
      terminal pro-B-type natriuretic peptide, and New York Heart Association class.
      Chronic kidney disease was also more prevalent in this group. Blood pressure was
      not related to the kidney function. CONCLUSIONS: Despite polytherapy, optimal
      blood pressure control was not achieved in the majority of patients. OHT patients
      have a high prevalence of hypertension, which should be treated adequately. More
      efforts should be made to optimize blood pressure control, particularly when
      other comorbidities are present. Blood pressure was not related to patient kidney
      function.

PMID- 25380931
TI  - Psychological predictors (personal recourses) of quality of life for heart
      transplant recipients.
AB  - BACKGROUND: Heart transplantation (HTx) has a significant impact on all areas of
      the operation, adjustment, and quality of life (QOL) in patients after heart
      transplantation. In the process of healing and coping with the new situation, it
      is important to have personal resources. AIM: The main objectives of this study
      were to assess subjective QOL of patients after HTx and to determine the
      relationship between personal resources and QOL in this group of patients.
      MATERIAL AND METHODS: The study included 121 patients who received a heart
      transplant. A standardized instrument used to measure the quality of life was the
      World Health Organization (WHO) QOL Brief Questionnaire. The personal resources
      and deficits were determined using the following research techniques:
      Antonovsky's Sense of Coherence (SOC), coping strategies for stress (Brief-COPE),
      Generalized Self Efficacy Scale (GSES), and Life Orientation Test (LOT-R). The
      data were analyzed statistically. RESULTS: The patients gained an average level
      of QOL (13.75). The results indicate a positive relationship between the QOL in
      all its domains and personal resources: a sense of coherence (r = 0.65; P < .05),
      optimism (r = 0.55; P < .05), self-efficacy (r = 0.58; P < .05), and strategies
      for coping (active coping [r = 0.41; P < .05], planning [r = 0.42; P < .05; P <
      .05], and positive revaluing [r = 0.40; P < .05]). The regression model explained
      56% of the predictors of QOL in patients after HTx. APPLICATIONS: It is necessary
      to strengthen personal resources in this group of patients as well as to detect
      early and treat symptoms of depression and to cope with stress.

PMID- 25380930
TI  - Dopamine and noradrenaline are unrelated to renalase, heart rate, and blood
      pressure in heart transplant recipients.
AB  - INTRODUCTION: Renalase may degrade catecholamines and regulate sympathetic tone
      and blood pressure. The aim of this study was to assess dopamine, norepinephrine,
      and renalase in 80 heart transplant recipients and 22 healthy volunteers and
      their correlations with heart rate, blood pressure control, type of hypotensive
      therapy, and renal function. PATIENTS AND METHODS: Renalase, dopamine, and
      norepinephrine were studied by using commercially available assays. RESULTS:
      Renalase levels were higher in heart transplant recipients compared with healthy
      volunteers, and noradrenaline levels were lower in the studied cohort patients
      than in the healthy volunteers. Noradrenaline was correlated with white blood
      cell count (r = -0.21, P < .05), copeptin (r = 0.41, P < .01), and left
      ventricular diameter (r = -0.29, P < .05), whereas dopamine was correlated in
      univariate analysis with white blood cell count (r = -0.22, P < .05), posterior
      wall of left ventricular diameter (r = 0.58, P < .01), and left atrium diameter
      (r = -0.31, P < .05). Neither noradrenaline nor dopamine was correlated with
      heart rate, blood pressure, kidney function, or New York Heart Association class.
      Noradrenaline was significantly higher in patients with elevated diastolic blood
      pressure (>90 mm Hg) compared with those with normal diastolic blood pressure (P
      < .05). Renalase was related to kidney function but was unrelated to
      catecholamines. CONCLUSIONS: Elevated renalase levels in heart transplant
      patients were related to kidney function but not linked to the sympathetic
      nervous system activity in this study population. In heart transplant recipients,
      these findings might suggest that sympathetic denervation and the modulation of
      beta-receptors persist.

PMID- 25380932
TI  - Post-transplantation body mass index in heart transplant recipients: determinants
      and consequences.
AB  - BACKGROUND: Heart transplantation (HTx) is an important treatment for end-stage
      chronic heart failure. After HTx, recipients frequently become obese. Gaining
      weight measured by body mass index (BMI) has been reported as a common phenomenon
      for patients before and after solid organ transplantation, becoming specifically
      significant for the long-term follow up after organ transplantation. In the long
      term following HTx, overweight and obesity may lead to increased risk of
      cardiovascular complications, developing metabolic syndrome-a topic well
      documented in previous studies. AIM: The aims of this study were to calculate the
      BMI in patients after HTx with follow up in our center and to assess potential
      predictors for overweight and obesity as well as their consequences. METHODS: A
      complete assessment of the BMI among all available heart transplant (HT)
      recipients (n = 169) was performed. Data were retrieved from patients' charts.
      Data were statistically analyzed. RESULTS: The sample mean age was 55.12 +/-
      13.34 years, mean years since transplantation being 10.70 +/- 5.26 years and the
      majority of study subjects were males (76.33%). Overall BMI was mean 26.33 +/-
      3.79. Based on the World Health Organization (WHO) classification, 32.54% were
      normal, 46.74% were overweight, and 18.34% were obese. We did not observe a
      statistical difference between BMI before and after transplantation, between
      immunosuppressive protocol, and receipt of steroids. We observed an association
      between BMI and level of fasting glucose (r = 0.35; P < .05) and difference
      between BMI and gender as well as the presence of cardiovascular diseases.
      CONCLUSIONS: Overweight and obesity after HTx are common and reflect a risk
      factor for cardiac allograft vasculopathy and other cardiovascular diseases as
      well as metabolic syndrome among HT recipients.

PMID- 25380933
TI  - Fibroblast growth factor 23 and Klotho as cardiovascular risk factors in heart
      transplant recipients.
AB  - BACKGROUND: Fibroblast growth factor (FGF) 23 is one of the most recently
      discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for
      cardiovascular diseases and thus mortality. Klotho is an essential coreceptor for
      FGF23 and at the same time it is known as a "longevity" hormone. There are no
      data considering FGF23 and Klotho roles in heart transplant (HT) recipients. The
      aim of this study was to assess Klotho and FGF23 serum concentration in heart
      transplant recipients depending on immunosuppressive therapy regimen and
      comorbidities. METHODS: Eighty-four stable heart transplant recipients were
      enrolled in the study; 22 healthy volunteers served as control subjects. FGF23
      and Klotho protein concentration, markers of renal function, such as cystatin C
      and neutrophil gelatinase-associated lipocalin (NGAL), and heart failure markers,
      such as copeptine and N-termiinal pro-B-type natriuretic peptide (NT-proBNP),
      were evaluated. RESULTS: FGF23 concentration was significantly higher in the HT
      group whereas Klotho protein was significantly lower. FGF23 correlated with
      creatinine level (r = 0.72; P < .001), estimated glomerular filtration rate
      (eGFR; r = -0.32; P < .01), cystatin C (r = 0.36; P < .01), NGAL (r = 0.51; P <
      .001), hemoglobin (r = -0.39; P < .001), NT-proBNP (r = 0.51; P < .001), high
      density lipoprotein (HDL; r = 0.27; P < .05), intraventricular septum thickness
      (r = 0.42; P < .01) and right ventricular systolic pressure (r = 0.34; P < .05).
      Klotho protein correlated only with age (r = -0.21; P < .05), creatinine (r = 
      0.21; P < .05), and eGFR (r = -0.31; P < .01). FGF23 concentration was
      significantly higher in patients with eGFR <60 mL/min whereas Klotho protein was
      significantly lower. FGF23 predictors were renal function (creatinine
      concentration; beta = 0.45; P = .0001), HDL (beta = 0.33; P = .003),
      intraventricular septum thickness (beta = 0.38; P = .0003), and right ventricular
      systolic pressure (beta = 0.34; P = .003), explaining 70% of FGF23 variability.
      CONCLUSIONS: FGF23/Klotho system disorders in HT recipients are related to
      cardiovascular system function and kidney failure and could cause increased risk
      of cardiovascular disease.

PMID- 25380934
TI  - Growth differentiation factor 15 is related to anemia and iron metabolism in
      heart allograft recipients and patients with chronic heart failure.
AB  - BACKGROUND: Growth differentiation factor (GDF) 15 was recently identified as a
      hepcidin-suppression factor that is expressed at high levels in patients with
      ineffective erythropoiesis. Hepcidin is a small defensin-like peptide whose
      production by hepatocytes is modulated in response to anemia, hypoxia, or
      inflammation. The aim of this study was to assess GDF15 levels and its
      correlation with iron parameters in 134 stable heart transplant recipients
      compared with 157 patients with chronic heart failure (CHF). METHODS: Complete
      blood count, urea, creatinine, lipids, fasting glucose, and iron status were
      studied with the use of standard laboratory methods. We assessed GDF15, hepcidin,
      and soluble transferrin receptor (sTfR) with commercially available assays.
      RESULTS: Mean levels of GDF15 and hepcidin were significantly higher in heart
      allograft recipients compared with patients with chronic heart failure (P <
      .001). GDF15 was significantly higher in patients with anemia compared with
      nonanemic counterparts in both groups. In univariate analysis in heart transplant
      recipients, GDF15 was related to kidney function, age, time after
      transplantation, hepcidin, sTfR, hemoglobin, transferrin saturation, ejection
      fraction (EF), and New York Heart Association functional class. GDF15 was not
      related to serum iron or ferritin in both groups. In multivariate analysis, sTfR,
      creatinine, and age were found to be predictors of GDF15. In univariate analysis
      in CHF patients, GDF15 was related to creatinine, erythrocyte count, hemoglobin,
      hepcidin, and total iron binding capacity and tended to correlate with EF. In
      multivariate analysis, hepcidin, creatinine, and EF were found to be predictors
      of GDF15 in CHF. CONCLUSIONS: GDF15, by affecting iron status, might be involved
      in the pathogenesis of anemia in patients with cardiovascular pathology.

PMID- 25380935
TI  - Zonulin and iron metabolism in heart transplant recipients.
AB  - BACKGROUND: In patients after heart transplantation, anemia is relatively common
      and is associated with impaired kidney function, subclinical inflammatory state,
      and immunosuppressive treatment. Zonulin-prehaptoglibin-2 is newly discovered
      protein with poorly defined function. Hemoglobin binds haptoglobin, and this
      stable complex prevents oxidative stress caused by hemoglobin. Zonulin is
      necessary for integrity of intracellular tight junction in the gut. Taking into
      consideration iron metabolism, including its absorption in the gut, the aim of
      this study was to assess zonulin levels in heart transplant recipients and their
      possible correlations with iron status, immunosuppressive therapy, and kidney
      function. METHODS: The study was performed with 80 stable heart transplant
      recipients and 22 healthy volunteers. Zonulin, iron status, and inflammatory
      markers were assessed with the use of commercially available kits. RESULTS:
      Zonulin correlated with intraventricular diameter (r = 0.30; P < .05), right
      ventricle systemic pressure (r = 0.27; P < .05), and hemoglobin (r = 0.21; P <
      .05). There were no correlations between zonulin and iron status. Zonulin was
      significantly lower in heart transplant recipients than in healthy volunteers (P
      < .001). Kidney function, immunosuppressive regimen, New York Heart Association
      functional class, sex, and presence of anemia did not affect zonulin level.
      CONCLUSIONS: Zonulin, despite its effect on the absorption of different nutrients
      and other substances and hypothethic role in oxidative stress, seems not to play
      a role in the pathogenesis of anemia in heart transplant recipients. Its
      physiologic role remains obscure.

PMID- 25380936
TI  - YKL-40, a novel marker of cardiovascular complications, is related to kidney
      function in heart transplant recipients.
AB  - BACKGROUND: YKL-40 is an inflammatory glycoprotein involved in endothelial
      dysfunction and expressed in macrophages in the earliest lesions of
      atherosclerosis. Elevated serum YKL-40 levels are independently associated with
      the presence and extent of coronary artery disease and cardiovascular mortality.
      Because there are no data on heart transplant recipients and because they are
      prone to cardiovascular complications, the aim of this study was to assess YKL-40
      in this population with particular attention to its relationship with endothelial
      damage. We studied 84 patients after heart transplantation. Healthy volunteers
      served as control subjects. METHODS: Complete blood count, urea, creatinine,
      lipids, fasting glucose, N-terminal pro-B-type natriuretic peptide (NT-proBNP),
      and iron status were studied with the use of standard laboratory methods. We
      assessed YKL-40, copeptin, markers of inflammation high sensitivity C-reactive
      protein (hsCRP) and interleukin (IL) 6, and markers of endothelial cell injury
      von Willebrand factor (vWF) and midkine with the use of commercially available
      assays. RESULTS: Mean levels of YKL-40, IL-6, vWF, and hsCRP were significantly
      higher in heart allograft recipients than in the control group (P < .001). In
      univariate analysis, YKL-40 was related to kidney function (creatinine, r = 0.63
      [P < .001]; estimated glomerular filtration rate, r = -0.44 [P < .001]), NT
      proBNP (r = 0.45; P < .001), age (r = 0.33; P < .01), time after transplantation
      (r = 0.23; P < .05), copeptin (r = -0.42; P < .001), soluble transferrin receptor
      (r = 0.24; P < .05), hemoglobin (r = -0.42; P < .001), transferrin (r = -0.31; P
      < .01), haptoglobin (r = 0.39; P < .001), cystatin C (r = 0.55; P < .001),
      ejection fraction (r = -0.28; P < .05), New York Heart Association functional
      class (r = -0.41; P < .01), hsCRP (r = 0.26; P < .05), IL-6 (r = 0.23; P < .05),
      vWF (r = -0.40; P < .001), and midkine (r = 0.33; P < .01). In multivariate
      analysis, only creatinine was found to be a predictor of YKL-40 (beta = 0.59; P =
      .02), explaining 56% of the variation in YKL-40 levels in heart allograft
      recipients. CONCLUSIONS: YKL-40 may contribute to the enhanced risk of
      cardiovascular complications mainly owing to impaired renal function in patients
      after heart transplantation.

PMID- 25380937
TI  - Fractal analysis of heart graft acute rejection microscopic images.
AB  - BACKGROUND: Endomyocardial biopsy to evaluate rejection in the transplanted heart
      is accepted at the "gold standard." The complexity of microscopic images
      suggested using digital methods for precise evaluating of acute rejection
      episodes with numerical representation. The aim of the present was study to
      characterize digitally acute rejection of the transplanted heart using
      complexity/fractal image analysis. MATERIAL AND METHODS: Biopsy samples harvested
      form 40 adult recipients after orthotropic heart transplantation were collected
      and rejection grade was evaluated according to the International Society for
      Heart and Lung Transplantation (0, 1a, 1b, or 3a) at transverse and longitudinal
      sections. Fifteen representative digital microscope images from each grade were
      collected and analyzed after Sobel edge detection and binarization. RESULTS: Only
      mean fractal dimension showed a progressive and significant increase and
      correlation based on rejection grade using longitudinal sections. Lacunarity and
      number of foreground pixels showed unequivocal results. CONCLUSION: Mean fractal
      diameter could serve as auxiliary digital parameter for grading of acute
      rejection in the transplanted heart.

PMID- 25380938
TI  - Autologous osteoblast transplantation, an innovative method of bone defect
      treatment: role of a tissue and cell bank in the process.
AB  - BACKGROUND: The idea of cell treatment of various diseases and medical conditions
      has become very popular. Some procedures are well established, as is autologous
      chondrocyte implantation, whereas others are still in the process of early
      development, laboratory experiments, and some clinical trials. METHODS: This
      report is devoted to an example of an emerging cell treatment: bone augmentation
      with the use of autologous cells and its legal and technical background. Various
      requirements set by law must be met by tissue banks performing cell seeding of
      grafts. In Europe, the requirements are described in directives 2004/23/EC,
      2006/17/EC, 2006/86/EC, and in the regulation 2007/1394/EC. RESULTS:
      Revitalization of biostatic allografts gives new, promising tools for creation of
      functional parts of organs; brings the methodology used in tissue banks closer to
      tissue engineering; places the enterprise in the mainstream of advanced
      biotechnology; allows the full potential of tissue allografts; and opens a new,
      large area for clinical and laboratory research. Cell and tissue processing also
      have a financial impact on the treatment: it produces additional expenditures.
      CONCLUSIONS: Clinical effectiveness will be the most decisive factor of whether
      this innovative treatment will be applied in a particular type of medical
      condition. From a tissue establishment perspective, the most important issue is
      to develop a procedure that ensures safety for the patient in graft quality
      terms.

PMID- 25380939
TI  - Microbial contamination of peripheral blood and bone marrow hematopoietic cell
      products and environmental contamination in a stem cell bank: a single-center
      report.
AB  - Hematopoietic stem cells (HSC) derived from peripheral blood (PB) and bone marrow
      (BM) are frequently used for autologous and allogenic transplantations.
      Establishing quality control at appropriate steps of the stem cell preparation
      process is crucial for a successful transplantation. Microbial contamination of
      haematopoietic stem cells is rare but could cause a potentially mortal
      complication of a stem cells transplantation. We investigated the microbiological
      contamination of PB (291 donations) and BM (39 donations) products. Microbial
      cultures of 330 donations between January 2012 and June 2013 were retrospectively
      analyzed after the collection and preparation steps. The microbiological analysis
      was performed with an automated system. Hematopoietic stem cells were processed
      in a closed system. Additionally, in this report the environment of the working
      areas of stem cell preparation was monitored. We analyzed microbial contamination
      of the air in a class I laminar air flow clean bench at the time of preparation
      and in the laboratory once per month. We reported 9 (2.73%) contaminated HSC
      products. The most frequent bacteria isolated from PB and BM products were
      Bacillus species. Coagulase-negative staphylococci and Micrococcus species were
      the most frequent micro-organisms detected in the air microbial control.
      Microbial control results are necessary for the safety of hematopoietic stem cell
      products transplantation. Microbial control of hematopoietic stem cell products
      enables an early contamination detection and allows for knowledgeable decision
      making concerning either discarding the contaminated product or introducing an
      efficient antibiotic therapy. Each step of cell processing may cause a bacterial
      contamination. A minimum of manipulation steps is crucial for increasing the
      microbial purity of the transplant material. Also, the air contamination control
      is essential to ensure the highest quality standards of HSC products preparation.

PMID- 25380940
TI  - High-dose melphalan and autologous hematopoietic stem cell transplantation in
      primary amyloidosis: single-center results.
AB  - BACKGROUND: Systemic immunoglobulin light-chain amyloidosis (AL) is a plasma cell
      dyscrasia resulting in multisystem organ failure and death. Autologous
      hematopoietic stem-cell transplantation (ASCT) has been widely used to treat
      patients with AL. However, treatment-related mortality remains high and reported
      series are subject to selection bias. METHODS: To define the role of patient
      selection in stem cell transplantation, we evaluated 24 consecutive AL patients
      transplanted at our center. RESULTS: Complete hematologic response was achieved
      in all 20 patients surviving >100 days posttransplantation. The 1-year overall
      survival (OS) rate after ASCT was 78.5%. The 5- and 10-year progression-free and
      OS rates were 57% and 47%, respectively. Treatment-related deaths owing to
      cardiovascular problems occurred in 16% of cases. CONCLUSION: ASCT for AL
      amyloidosis can be safely performed in experienced transplantation centers, and
      increased risk is associated mainly with cardiovascular system involvement.

PMID- 25380941
TI  - Biosimilar granulocyte colony-stimulating factor is effective in reducing the
      duration of neutropenia after autologous peripheral blood stem cell
      transplantation.
AB  - BACKGROUND: Autologous peripheral blood stem cell transplantation (APBSCT) is the
      standard of therapy for patients with multiple myeloma and refractory Hodgkin's
      and non-Hodgkin's lymphomas. Granulocyte colony-stimulating factor (G-CSF) is
      widely used to accelerate hematopoietic recovery after transplantation and to
      reduce the morbidity and mortality associated with prolonged neutropenia.
      Biosimilar G-CSF is approved for the same indications as the originator G-CSF.
      This is one of the first reported uses of a biosimilar G-CSF for neutrophil
      recovery after APBSCT. METHODS: A total of 23 consecutive patients with
      hematological malignancy (multiple myeloma, Hodgkin's and non-Hodgkin's
      lymphomas, and acute myelogenous leukemia) were recruited at the Department of
      Haematooncology and Bone Marrow Transplantation at the Medical University of
      Lublin. Patients (12 men and 11 women; median age, 47 +/- 13 years) received
      biosimilar G-CSF (Zarzio, Sandoz Biopharmaceuticals) after myeloablative
      chemotherapy (primarily BiCnU, etoposide, cytarabine, and melphalan or melphalan
      140/200 mg/m(2)) followed by PBSCT. The median number of transplanted CD34+ cells
      was 4.2 +/- 0.8 * 10(6)/kg body wt. G-CSF therapy was started when absolute
      neutrophil count (ANC) was <0.5 * 10(9)/L and was continued until ANC reached
      >1.5 * 10(9)/L for 3 consecutive days. Hematopoietic recovery parameters were
      compared with those in the control group, which consisted of 23 consecutive
      patients transplanted in the period before the biosimilar G-CSF group and
      receiving originator G-CSF (Neupogen, Amgen). RESULTS: The mean duration of
      treatment with biosimilar and originator G-CSF was 14.4 +/- 5.1 and 18.6 +/- 11.5
      days, respectively (P = .43). The adverse event profile was comparable between
      the biosimilar G-CSF and originator G-CSF groups, with similar occurrence of
      neutropenic fever (5 versus 6 patients) and bone pain (7 patients in each group).
      One patient in the biosimilar group had neutropenic enterocolitis and sepsis.
      There was no case of death in either group. Granulocyte recovery in the study
      group was as follows: mean days to ANC >0.5 * 10(9)/L was 13.0 +/- 4.0 days; to
      ANC >1.5 * 10(9)/L, 13.6 +/- 4.5 days; and to ANC >1.5 * 10(9)/L, 14.0 +/- 4.7
      days. Mean duration until platelet recovery >20 * 10(9)/L was 16.1 +/- 4.4 days.
      There were no statistically significant differences between the biosimilar and
      originator G-CSF groups in hematopoietic recovery parameters. CONCLUSIONS:
      Biosimilar G-CSF is safe and effective in reducing the duration of neutropenia in
      patients undergoing myeloablative therapy followed by APBSCT and probably in cost
      savings in transplantation budgets.

PMID- 25380942
TI  - Transplantation of keratinocyte spore-like stem cells.
AB  - BACKGROUND: Wound granulation tissue should be covered by epidermal cells
      migrating from the basal layer of the epidermis or hair "bulge" of the wound
      edge. However, new epidermal islands are frequently formed on the granulation
      tissue remote from the wound edge. Thus, current theory of "bulge"-originating
      stem cells does not necessarily correspond to the histological pictures of the
      healing wound. We took imprints of a leg ulcer surface and found single
      dispersed, large nucleated cells, some of them in mitosis. These cells resembled
      those from epidermal spinosum layer. The question arouse as to whether these
      cells might be the "spore-like" stem cells creating epidermal island. We found
      similarly shaped cells among the keratinocyte preserved in pulverized sodium
      chloride as the only surviving population in culture and revealing enzymatic
      activity. The aim of this work was to study whether the population of human
      keratinocytes surviving sodium chloride preservation and transplanted to SCID
      mice may form epidermis. METHODS: The 12-month sodium chloride-preserved and
      cultured keratinocytes (KC) were transplanted to the wound on the dorsum of SCID
      mice for 14 and 21 days. RESULTS: Ninety-five percent of cultured KC were
      enzymatically active "large" cells; they did not express p63 and CD29 claimed as
      specific for stem cells, and they did not proliferate. Transplanted to the center
      of the wound, they formed small KC islands and became confluent after 14 days.
      CONCLUSIONS: The "large" epidermal keratinocytes survived the 12-month
      preservation in anhydrous sodium chloride. Transplanted to the wound, they formed
      epidermal islands of human phenotype. These cells may be the so-called "spore
      like" stem cells.

PMID- 25380943
TI  - Significant infections after hand transplantation in a Polish population.
AB  - The study was conducted to assess serious infectious complications in five hand
      allograft recipients (four males, one female, age 40 +/- 10 years), transplanted
      between 2006 and 2010. All donors and recipients were positive but one for
      cytomegalovirus (CMV) immunoglobulin G. All recipients received immunosuppressive
      therapy basiliximab, tacrolimus, mycophenolate mofetil and methylprednisolone.
      Until May 2013, there were four cases of severe infections requiring
      hospitalization. One patient developed CMV infection on the 28th postoperative
      day. Despite therapy with ganciclovir and prophylaxis with valganciclovir,
      reinfection episodes occurred both 4 weeks and 7 months later. The female
      recipient developed CMV infection 8 months after hand transplantation. After 3
      weeks of ganciclovir treatment, the polymerase chain reaction results remained
      negative. We found that the CD4/CD8 T lymphocytes ratio differs in those two
      patients who had developed CMV disease in the past in comparison to the three
      remaining hand transplant recipients (mean 0.46 versus 1.7, respectively).
      Moreover, the ratio of patients who were CD4-8 negative to total T lymphocytes in
      CMV recovered patients was two-fold higher compared to the remaining recipients
      (10.0 versus 4.4, respectively). The female recipient was also hospitalized
      because of acute tonsillitis 25 months after hand transplantation, and
      successfully treated with amoxicillin clavulanate. The third recipient was
      hospitalized because of severe acute pain involving right lower limb, especially
      foot, 74 months after hand transplantation. After 48 hours, a painful vesicular
      rash occurred on the plantar as well as dorsal surface of right foot and herpes
      zoster was diagnosed. Immunosuppressive therapy after hand transplantation may be
      complicated by serious infections. CMV disease was associated with persistent
      alterations in T lymphocyte subsets.

PMID- 25380944
TI  - Impact of immunosuppressive treatment on the cardiovascular system in patients
      after hand transplantation.
AB  - BACKGROUND: Cardiovascular disease is a major cause of mortality in solid organ
      allograft recipients. Hand transplantation is not a lifesaving procedure, thus
      the effect of long-term immunosuppression on the cardiovascular system in these
      patients should be monitored. The aim of this study was to evaluate the
      morphology and function of heart and blood vessels in patients after hand
      transplantation. METHODS: The study included 5 patients at ages 32 to 58 years,
      mean 39 years, who underwent hand transplantation between 2006 and 2010.
      Immunosuppressive treatment included basiliximab in induction and tacrolimus,
      mycophenolate mofetil, and prednisone. Cardiac status was assessed by
      echocardiography (according to the American Society of Echocardiography) and
      cardiac biomarkers. Blood vessels were estimated by carotid intima-media
      thickness, pulse wave velocity, and brachial artery flow-mediated dilatation
      (FMD). The examinations were performed at 28 to 79 (mean 43) months after
      transplantation. RESULTS: Cardiovascular risk factors were observed in all
      patients after transplantation: 2 had insulin-dependent diabetes, 3 developed
      dyslipidemia and hypertension, 2 had chronic kidney disease stage 3. Concentric
      left ventricular hypertrophy was found in 1 and ventricular concentric remodeling
      in 4 patients. Impaired diastolic function (E/e' > 8) was observed in 2 patients.
      The index volume of the left atrium was higher in all patients. The cardiac
      biomarkers N-terminal pro-brain natriuretic peptide, C-reactive protein, and
      troponins were within normal range. Carotid intima-media thickness was higher in
      1 patient and normal in 4 patients. Arterial stiffness measured by pulse wave
      velocity was not increased in all patients. Native brachial artery FMD response,
      an index of endothelium-dependent function, was abnormal in 2 patients, but in
      the transplanted extremity FMD was abnormal in 4 patients. CONCLUSIONS:
      Pathologic changes in cardiac structures were found in all patients, but the
      arterial wall changes and endothelial dysfunction were observed in some patients.
      Patients after hand transplantation are at higher risk for cardiovascular
      disease.

PMID- 25380945
TI  - Intrasplenic transplanted adult rat isolated hepatocyte fraction but not
      cholangiocytes forms bile canaliculi.
AB  - BACKGROUND: Hepatocyte transplantation (HT) has been performed in patients with
      liver-based metabolic disease and acute liver failure as a potential alternative
      to liver transplantation in countries in which ethical regulations do not allow
      organ transplantation. One of the problems remains that substances normally
      secreted by the surviving hepatocytes to bile cannot be removed because of lack
      of bile canaliculi. We found that ligation of the recipient's common bile duct in
      hepatocyte transplantation recipients is followed by formation of bile
      canaliculi. The question arose as to whether the signal released from the
      obstructed bile vasculature activated the transplanted hepatocytes (HC) or
      cholangiocyte (CH) to form bile canaliculi. METHODS: We transplanted separately
      isolated autologous HC and CH to spleens and observed the structural organization
      of the grafted cells. RESULTS: HC formed glycogen-rich clusters but not cords
      usually not attached to the CH of the new bile canaliculi. Separate clusters of
      bile canaliculi with keratin 7 and 19-positive and gamma-glutamyl transpeptidase
      positive cells were observed. Transplanted CH remained keratin 7 and 19-positive
      and gamma-glutamyl transpeptidase positive but did not form canaliculi.
      CONCLUSIONS: The transplanted HC fraction may contain hepatic progenitor cells
      for cholangiocytes, but they become activated only under the condition of bile
      stasis by an as-yet undefined factor.

PMID- 25380946
TI  - Dramatic recurrence of cancer in a patient who underwent kidney transplantation-
      case report.
AB  - BACKGROUND: Besides cardiovascular diseases and infections, cancers are the main
      cause of death in patients after transplantation of a vascularized organ. After
      transplantation, usually de novo cancers develop. Recurrences of cancers that had
      been diagnosed and treated before transplantation are much rarer. In exceptional
      cases, cancer is transferred with the donor's organ. The epidemiology and the
      course of post-transplantation de novo neoplasia is relatively well known.
      However, the issue of recurrence of pre-transplantation cancer, which is
      significantly rarer and its course more individualized and difficult to predict,
      poses a challenge to contemporary transplantation. CASE REPORT: This paper
      presents an unexpectedly rapid recurrence of rare cancer-endometrial stromal
      sarcoma-that occurred shortly after transplantation of a kidney from a deceased
      donor to a patient who had undergone cancer treatment 7 years earlier. The
      dramatic course of the disease, complicated with recurrent massive thrombosis of
      the inferior vena cava and the right cardiac cavities, as well as pulmonary
      embolism and serious infectious complications, illustrates the difficulties
      related to qualifying patients with a history of malignancy for transplantation.
      CONCLUSIONS: Based on this case report, we attempt to find an answer to the
      question about the risk of cancer recurrence in patients receiving
      immunosuppressive therapy and find out how it can be minimized. Answering these
      questions is particularly important if the recurrent cancer is substantially more
      aggressive, cancer treatment options are limited, and the prognosis is poor due
      to lack of immunocompetence.

PMID- 25380947
TI  - Sebaceous carcinoma in patients receiving long-term immunosuppresive treatment:
      case report and literature review.
AB  - BACKGROUND: Sebaceous carcinoma (SC) is a very rare and aggressive malignant skin
      cancer that appears to occur with a greater frequency in the clinical setting of
      chronic immunosuppression; however, it is not reported in the literature as
      frequently as is squamous cell carcinoma (SCC). We report 2 cases of SC in organ
      transplant patients from clinical and histopathological points of view. METHODS:
      A 48-year-old patient after 3 renal transplantations (1986, 1986, and 1998) was
      presented to the Dermatology Department in 1999 because of a papillomatous lesion
      along her right upper eyelid. The lesion was excised. Histopathologically, it was
      diagnosed as a SC. There was no lymphovascular invasion and no metastasis;
      therefore no other treatment was included. No symptoms of recurrent disease were
      present 14 years since diagnosis. An 87-year-old patient after a renal
      transplantation in 1989 was referred to dermatologist in 1993 because of the
      lesion on his right temple. The lesion was excised; histopathologically, it was
      diagnosed as SC. Because of metastatic disease, he had a course of radiotherapy
      to the right side of the neck. The immunosuppressive drugs azathioprine and
      cyclosporine A were reduced. The patient died of metastatic disease 1 year later
      (3 years since diagnosis). Both patients had very high cumulative UV exposition
      during their lifetimes, and many skin cancers were diagnosed, especially SCC.
      RESULTS: It is necessary to realize that this cancer occurs more frequently in
      organ transplant patients, and its correct diagnosis is an essential issue
      because it has significantly more aggressive behavior than does SCC. In the 2
      presented patients, we observed very rapid progression of disease. Despite
      aggressive treatment and reduction of immunosuppressive drugs, the second patient
      died 3 years after diagnosis. CONCLUSIONS: Regular dermatological follow-up is
      required in the population of organ transplant patients to identify all skin
      tumors in the early stage.

PMID- 25380948
TI  - Fatal late-onset Pneumocystis pneumonia after rituximab: administration for
      posttransplantation recurrence of focal segmental glomerulosclerosis--case
      report.
AB  - Recurrence of focal segmental glomerulosclerosis (FSGS) is an important cause of
      graft loss after kidney transplantation. The management of patients with
      recurrent FSGS is not well established because there are no prospective
      randomized studies with a view to the impact of FSGS on graft survival. Recent
      studies suggest that rituximab, an anti-B-CD20 monoclonal antibody, may be a
      therapeutic alternative in selected cases resistant to conventional therapy.
      Opportunistic infections with rituximab have not been studied extensively, but
      recent studies suggest an increased risk for Pneumocystis jirovecii pneumonia
      (PJP) after rituximab therapy. We report the case of a kidney transplant
      recipient with recurrence of FSGS in the graft, in whom fatal PJP developed
      subsequent to treatment with rituximab. Our patient was treated with
      plasmapheresis and a complex immunosuppressive drug scheme for the recurrence of
      FSGS in transplanted kidney. However, this treatment had no effect on the amount
      of proteinuria, which increased to a maximum of 15 g/d after 18 session of
      plasmapheresis. Thereafter, 500 mg intravenously (IV) of rituximab was
      administered at 4-week intervals. The number of CD19-positive B lymphocytes
      decreased from 9% to 0.57%. Two months after the second dose of rituximab,
      proteinuria decreased to 2.1 g/d. Ten months after transplantation and 5 months
      after the first dose of rituximab was administered, severe PJP pneumonia
      developed and the patient died despite all efforts with antibiotic therapy. It
      seems essential that all renal transplant recipients treated with rituximab
      should currently be considered at an increased risk for PJP. This case suggests
      that prolonged or restarted prophylaxis for PJP should be recommended not only
      after conventional treatment for acute rejection episodes but also after use of
      rituximab in combination with other immunosuppressive therapy as well.

PMID- 25380949
TI  - Everolimus in immunosuppressive treatment after kidney transplantation in a
      patient with tuberous sclerosis: case report.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is an inherited disorder caused by
      mutations of TSC1 or TSC2 genes, resulting in constitutive activation of the
      mammalian target of rapamycin (mTOR) and impairment of the cell cycle. As a
      consequence, hamartomatous tumors of multiple organs may develop, but generally
      skin, brain, kidneys, and lungs are involved. mTOR inhibitors (mTOR-I,
      rapamycin/everolimus) may correct underlying defects in TSC. Previous data prove
      benefits and safety of mTOR-I on a wide spectrum of disease manifestations and
      effectiveness of rapamycin in TSC patients after kidney transplantation (KT).
      METHODS: We report the first case of a patient with TSC receiving everolimus
      initiated in immunosuppressive treatment at the time of KT. In April 2012, the 34
      year-old female TSC patient, after bilateral nephrectomy due to polycystic
      kidneys and skin lesions related to TSC, was transplanted with a renal graft from
      a deceased donor (PRA, 0%; MM A/B/DR,1/2/0). Initial immunosuppressive treatment
      consisted of basiliximab, methylprednisolone, tacrolimus, and everolimus.
      RESULTS: The early postoperative period was complicated by delayed graft
      function. Creatinine level at discharge was 1.39 mg/dL, with stable graft
      function in subsequent months. Nine months after KT, inflammatory infiltration of
      the nephrectomy site (performed in 2011) with persistent effusion was observed.
      After 2 months of unsuccessful conservative treatment, the patient was converted
      from everolimus to mycophenolate mofetil with healing of local state. During 11
      months of everolimus treatment, no improvement of skin presentation of TSC was
      noticed. CONCLUSIONS: mTOR-I appear to be a treatment of choice in transplanted
      patients with TSC, although some complications precluding continuous mTOR-I
      therapy allowing its potential benefits, may appear.

PMID- 25380950
TI  - Human papillomavirus-related verrucous carcinoma in a renal transplant patient
      after long-term immunosuppression: a case report.
AB  - BACKGROUND: Verrucous carcinoma is a slow-growing tumor with 3 main
      localizations: Oral cavity, ano-urogenital region, and plantar surface of the
      foot. On the sole it may rise adjacent to viral warts and very often is mistaken
      for the common verruca plantaris. Although both conditions-viral warts and
      cutaneous squamous cell carcinoma-are often diagnosed in immunosuppressed
      patients, in literature we have found only 3 case reports of verrucous carcinoma
      in organ transplant recipients. CASE REPORT: We present a case of 26-year-old man
      after deceased donor renal transplantation with plantar verrucous carcinoma
      successfully treated with excision and 5% imiquimod.

PMID- 25380951
TI  - Tako-tsubo cardiomyopathy on the first day after renal transplantation - case
      report and literature review.
AB  - BACKGROUND: The etiology of tako-tsubo cardiomyopathy, defined as a transient
      left ventricular dysfunction in the absence of significant coronary artery
      stenosis, still remains unclear. This syndrome mainly occurs in postmenopausal
      women and is often associated with emotional stress or miscellaneous diagnostic
      and therapeutic procedures. Estimated prevalence of tako-tsubo cardiomyopathy is
      found in 1% to 2% of patients presenting with suspected acute coronary syndrome.
      So far there has been only one case report of tako-tsubo cardiomyopathy in a
      renal transplant recipient. CASE REPORT: We describe the case of a 68-year-old
      woman with a history of coronary artery disease and coronary artery bypass
      grafting in whom unspecific transient chest pain and hypotension were observed on
      the first day after renal transplantation. After transplantation, the patient was
      anuric with pulmonary congestion and toxic tacrolimus concentrations were
      observed. Electrocardiogram showed sinus rhythm with left bundle branch block
      (LBBB) that has not been described before. Plasma cardiac necrosis markers
      troponin I and creatine kinase MB were mildly elevated. Echocardiography showed
      severe left ventricular function impairment with characteristic shape of left
      ventricle. Subsequent cardiac catheterization revealed the absence of
      angiographic evidence of acute plaque rupture within both coronary arteries and
      bypass grafts. During the next few days there was marked clinical improvement
      with resolution of LBBB and full recovery of all biochemical parameters. On
      discharge, full functional recovery of the left ventricle in echocardiography was
      observed. Postulated mechanisms of tako-tsubo cardiomyopathy include
      catecholamine excess, coronary artery spasm, and microvascular dysfunction. On
      the other hand calcineurin inhibitors are known factors causing coronary
      epicardial endothelial dysfunction and negatively affecting vasomotor function.
      CONCLUSIONS: Tako-tsubo cardiomyopathy in patients after renal transplantation
      may be at least in part a manifestation of calcineurin inhibitor cardiotoxicity.

PMID- 25380952
TI  - Methylene blue usage in horseshoe kidney graft separation: case report.
AB  - Definitive diagnostics and strict procedures during kidney donor qualification
      are required. Nowadays, precise and accurate imaging techniques are at hand for
      every diagnostician. However, many studies have described intraoperative
      occurrence of horseshoe kidney. Although the harvesting procedure in the case of
      horseshoe kidney is not technically difficult, graft separation for successful
      renal transplantation is a challenge. The complex anatomy of malformed organs
      causes issues during kidney separation. This procedure may lead to damage of the
      collecting urinary system as well as vascularization damage. Separate graft
      transplantation is probable when a thin isthmus in a horseshoe kidney is present.
      Otherwise, poor graft function may occur. We present a technique for horseshoe
      kidney separation with the use of methylene blue for vascularization
      determination. The above-mentioned procedure was performed with the methylene
      blue solution dose injected into a single renal graft artery. Even with the
      malformed organ's thick isthmus, the exact incision line was identified, exposing
      vascular perfusion asymmetry and allowing precise renal graft separation. 

PMID- 25380953
TI  - When less is more--case report of successful renal transplantation from a living
      unrelated donor to a high-risk female recipient.
AB  - Qualification for kidney transplantation for patients with a long history of
      renal replacement therapy and numerous medical complications requires individual
      analysis of all contraindications and limitations as well as advantages of the
      procedure. In this case report, we analyze the qualification process and
      posttransplantation course of a 28-year-old female patient with end-stage renal
      failure due to reflux nephropathy, treated with renal replacement therapy since
      early childhood, who received her second kidney transplant with glomerular
      filtration rate <40 mL/min/1.73 m(2) from a living, unrelated donor in 2009.
      Despite the high risk of immunological and surgical complications, transplanting
      organs of borderline excretory capacity, and no human leukocyte antigen matching,
      significant health benefits were achieved. Procurement of a kidney with
      borderline filtering function reduces the risk of potential negative consequences
      of impaired remnant filtration in the living donor. Following the principle of
      procuring a kidney with worse parameters from the living donors, it is necessary
      to perform an examination evaluating the function of each kidney. Procurement of
      a kidney with significantly worse parameters requires an individual assessment of
      benefits for the recipient.

PMID- 25380954
TI  - Pregnancy in a patient with hepatic artery thrombosis after liver
      transplantation: a case report.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) increases the risk of complications
      and mortality after liver transplantation. The incidence for HAT is increased in
      patients with risk factors (vascular reconstructions, coagulation disorders and
      acute rejection episodes amongst others). Early retransplantation improves the
      prognosis for patients, but owing to lack of donors, surgical and interventional
      radiologic attempts to restore the patency of hepatic artery are made. The
      prognosis for the liver and the patient can also be improved by the development
      of collateral circulation. CASE REPORT: We describe a case of a 30-year-old woman
      with hepatic failure owing to Wilson disease. Liver transplantation with the use
      of vascular conduit made of donor's iliac arteries was complicated by an early
      HAT. Heterozygous factor V Leiden mutation was confirmed in the patient. Despite
      surgical and radiologic attempts to restore patency and despite treatment with
      fractioned heparin and aspirin, the hepatic artery remained occluded.
      Retransplantation was not considered, even though the patient was planning a
      pregnancy. After 1 year of observation of stable liver function, conversion from
      mycophenolate mofetil to azathioprine treatment, the patient was given consent
      for a high-risk pregnancy. DISCUSSION: The course of pregnancy was uneventful,
      with normal liver function parameters, without pathological bleedings. The
      patient was treated with doses of enoxaparin adjusted for the patient's weight.
      In the 34th week, owing to increasing concentration of bile acids, the pregnancy
      ended with a cesarean section. The newborn had 10-point APGAR score.

PMID- 25380955
TI  - Early goal-directed therapy based on endotracheal bioimpedance cardiography: a
      prospective, randomized controlled study in coronary surgery.
AB  - The objective was to compare the impact of an early goal-directed hemodynamic
      therapy based on cardiac output monitoring (Endotracheal Cardiac Output Monitor,
      ECOM) with a standard of care on postoperative outcome following coronary
      surgery. This prospective, controlled, parallel-arm trial randomized 100 elective
      primary coronary artery bypass grafting patients to a study group (ECOM; n = 50)
      or a control group (control; n = 50). In the ECOM group, hemodynamic therapy was
      guided by respiratory stroke volume variation and cardiac index given by the ECOM
      system. A standard of care was used in the control. Goal-directed therapy was
      started immediately after induction of anesthesia and continued until arrival in
      the intensive care unit (ICU). The primary endpoint was the time when patients
      fulfilled discharge criteria from hospital (possible hospital discharge).
      Secondary endpoints were the hospital discharge, the time to reach extubation,
      the length of stay in ICU, the number of major adverse cardiac events, and in
      hospital mortality. Patients in the ECOM group received more often fluid loading
      and dobutamine. The time to reach extubation was reduced in the ECOM group: 510
      min [360-1,110] versus 570 min [320-1,520], P = 0.005. No significant differences
      were found between both groups for possible hospital discharge [Hazard Ratio =
      0.96 (95 % CI 0.64-1.45)] and hospital discharge [Hazard Ratio = 1.20 (95 % CI
      0.79-1.81)]. A mini-invasive early goal-directed hemodynamic therapy based on
      ECOM can reduce the time to reach extubation but fails to significantly reduce
      the length of stay in hospital and the rate of major cardiac morbidity.

PMID- 25380956
TI  - TreeEFM: calculating elementary flux modes using linear optimization in a tree
      based algorithm.
AB  - MOTIVATION: Elementary flux modes (EFMs) analysis constitutes a fundamental tool
      in systems biology. However, the efficient calculation of EFMs in genome-scale
      metabolic networks (GSMNs) is still a challenge. We present a novel algorithm
      that uses a linear programming-based tree search and efficiently enumerates a
      subset of EFMs in GSMNs. RESULTS: Our approach is compared with the EFMEvolver
      approach, demonstrating a significant improvement in computation time. We also
      validate the usefulness of our new approach by studying the acetate overflow
      metabolism in the Escherichia coli bacteria. To do so, we computed 1 million EFMs
      for each energetic amino acid and then analysed the relevance of each energetic
      amino acid based on gene/protein expression data and the obtained EFMs. We found
      good agreement between previous experiments and the conclusions reached using
      EFMs. Finally, we also analysed the performance of our approach when applied to
      large GSMNs. AVAILABILITY AND IMPLEMENTATION: The stand-alone software TreeEFM is
      implemented in C++ and interacts with the open-source linear solver COIN-OR
      Linear program Solver (CLP).

PMID- 25380957
TI  - Joint amalgamation of most parsimonious reconciled gene trees.
AB  - MOTIVATION: Traditionally, gene phylogenies have been reconstructed solely on the
      basis of molecular sequences; this, however, often does not provide enough
      information to distinguish between statistically equivalent relationships. To
      address this problem, several recent methods have incorporated information on the
      species phylogeny in gene tree reconstruction, leading to dramatic improvements
      in accuracy. Although probabilistic methods are able to estimate all model
      parameters but are computationally expensive, parsimony methods-generally
      computationally more efficient-require a prior estimate of parameters and of the
      statistical support. RESULTS: Here, we present the Tree Estimation using
      Reconciliation (TERA) algorithm, a parsimony based, species tree aware method for
      gene tree reconstruction based on a scoring scheme combining duplication,
      transfer and loss costs with an estimate of the sequence likelihood. TERA
      explores all reconciled gene trees that can be amalgamated from a sample of gene
      trees. Using a large scale simulated dataset, we demonstrate that TERA achieves
      the same accuracy as the corresponding probabilistic method while being faster,
      and outperforms other parsimony-based methods in both accuracy and speed. Running
      TERA on a set of 1099 homologous gene families from complete cyanobacterial
      genomes, we find that incorporating knowledge of the species tree results in a
      two thirds reduction in the number of apparent transfer events.

PMID- 25380958
TI  - Development of a robust classifier for quality control of reverse-phase protein
      arrays.
AB  - MOTIVATION: High-throughput reverse-phase protein array (RPPA) technology allows
      for the parallel measurement of protein expression levels in approximately 1000
      samples. However, the many steps required in the complex protocol (sample lysate
      preparation, slide printing, hybridization, washing and amplified detection) may
      create substantial variability in data quality. We are not aware of any other
      quality control algorithm that is tuned to the special characteristics of RPPAs.
      RESULTS: We have developed a novel classifier for quality control of RPPA
      experiments using a generalized linear model and logistic function. The outcome
      of the classifier, ranging from 0 to 1, is defined as the probability that a
      slide is of good quality. After training, we tested the classifier using two
      independent validation datasets. We conclude that the classifier can distinguish
      RPPA slides of good quality from those of poor quality sufficiently well such
      that normalization schemes, protein expression patterns and advanced biological
      analyses will not be drastically impacted by erroneous measurements or systematic
      variations. AVAILABILITY AND IMPLEMENTATION: The classifier, implemented in the
      "SuperCurve" R package, can be freely downloaded at
      http://bioinformatics.mdanderson.org/main/OOMPA:Overview or http://r-forge.r
      project.org/projects/supercurve/. The data used to develop and validate the
      classifier are available at http://bioinformatics.mdanderson.org/MOAR.

PMID- 25380959
TI  - PyFDAP: automated analysis of fluorescence decay after photoconversion (FDAP)
      experiments.
AB  - We developed the graphical user interface PyFDAP for the fitting of linear and
      non-linear decay functions to data from fluorescence decay after photoconversion
      (FDAP) experiments. PyFDAP structures and analyses large FDAP datasets and
      features multiple fitting and plotting options. AVAILABILITY AND IMPLEMENTATION:
      PyFDAP was written in Python and runs on Ubuntu Linux, Mac OS X and Microsoft
      Windows operating systems. The software, a user guide and a test FDAP dataset are
      freely available for download from http://people.tuebingen.mpg.de/mueller-lab.

PMID- 25380960
TI  - IntSide: a web server for the chemical and biological examination of drug side
      effects.
AB  - SUMMARY: Drug side effects are one of the main health threats worldwide, and an
      important obstacle in drug development. Understanding how adverse reactions occur
      requires knowledge on drug mechanisms at the molecular level. Despite recent
      advances, the need for tools and methods that facilitate side effect anticipation
      still remains. Here, we present IntSide, a web server that integrates chemical
      and biological information to elucidate the molecular mechanisms underlying drug
      side effects. IntSide currently catalogs 1175 side effects caused by 996 drugs,
      associated with drug features divided into eight categories, belonging to either
      biology or chemistry. On the biological side, IntSide reports drug targets and
      off-targets, pathways, molecular functions and biological processes. From a
      chemical viewpoint, it includes molecular fingerprints, scaffolds and chemical
      entities. Finally, we also integrate additional biological data, such as protein
      interactions and disease-related genes, to facilitate mechanistic
      interpretations. AVAILABILITY AND IMPLEMENTATION: Our data and web resource are
      available online (http://intside.irbbarcelona.org/). CONTACT:
      patrick.aloy@irbbarcelona.org SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25380961
TI  - Ulysses: accurate detection of low-frequency structural variations in large
      insert-size sequencing libraries.
AB  - MOTIVATION: The detection of structural variations (SVs) in short-range Paired
      End (PE) libraries remains challenging because SV breakpoints can involve large
      dispersed repeated sequences, or carry inherent complexity, hardly resolvable
      with classical PE sequencing data. In contrast, large insert-size sequencing
      libraries (Mate-Pair libraries) provide higher physical coverage of the genome
      and give access to repeat-containing regions. They can thus theoretically
      overcome previous limitations as they are becoming routinely accessible.
      Nevertheless, broad insert size distributions and high rates of chimerical
      sequences are usually associated to this type of libraries, which makes the
      accurate annotation of SV challenging. RESULTS: Here, we present Ulysses, a tool
      that achieves drastically higher detection accuracy than existing tools, both on
      simulated and real mate-pair sequencing datasets from the 1000 Human Genome
      project. Ulysses achieves high specificity over the complete spectrum of variants
      by assessing, in a principled manner, the statistical significance of each
      possible variant (duplications, deletions, translocations, insertions and
      inversions) against an explicit model for the generation of experimental noise.
      This statistical model proves particularly useful for the detection of low
      frequency variants. SV detection performed on a large insert Mate-Pair library
      from a breast cancer sample revealed a high level of somatic duplications in the
      tumor and, to a lesser extent, in the blood sample as well. Altogether, these
      results show that Ulysses is a valuable tool for the characterization of somatic
      mosaicism in human tissues and in cancer genomes.

PMID- 25380962
TI  - CytoCom: a Cytoscape app to visualize, query and analyse disease comorbidity
      networks.
AB  - CytoCom is an interactive plugin for Cytoscape that can be used to search,
      explore, analyse and visualize human disease comorbidity network. It represents
      disease-disease associations in terms of bipartite graphs and provides
      International Classification of Diseases, Ninth Revision (ICD9)-centric and
      disease name centric views of disease information. It allows users to find
      associations between diseases based on the two measures: Relative Risk (RR) and
      [Formula: see text]-correlation values. In the disease network, the size of each
      node is based on the prevalence of that disease. CytoCom is capable of clustering
      disease network based on the ICD9 disease category. It provides user-friendly
      access that facilitates exploration of human diseases, and finds additional
      associated diseases by double-clicking a node in the existing network. Additional
      comorbid diseases are then connected to the existing network. It is able to
      assist users for interpretation and exploration of the human diseases by a
      variety of built-in functions. Moreover, CytoCom permits multi-colouring of
      disease nodes according to standard disease classification for expedient
      visualization.

PMID- 25380963
TI  - ECG-synchronized CT angiography in 324 consecutive pediatric patients: spectrum
      of indications and trends in radiation dose.
AB  - The aim of the study is to describe the spectrum of indications for pediatric ECG
      synchronized CT angiography (CTA), the main determinants of radiation exposure,
      and trends in radiation dose over time at a single, tertiary referral center. The
      study was IRB approved and HIPAA compliant with informed consent waived. Between
      2005 and 2013, 324 pediatric patients underwent ECG-synchronized CTA to evaluate
      known or suspected cardiovascular abnormalities (109 female, median age 8.1
      years). The effective dose (ED) was calculated using age-specific correction
      factors. Univariate and multivariate regression analyses were performed to
      identify predictors of radiation dose. The most common primary indications for
      the CTA examinations included known or suspected coronary pathologies (n = 166),
      complex congenital heart disease (n = 73), and aortic pathologies (n = 41).
      Median radiation exposure decreased from 12 mSv for patients examined in the
      years 2005-2007 to 1.2 mSv for patients examined in the years 2011-2013 (p <
      0.001). Patients scanned using a tube potential of 80 kV (n = 259) had a
      significantly lower median radiation dose (1.4 mSv) compared to patients who were
      scanned at 100 kV (n = 46, median 6.3 mSv) or 120 kV (n = 19, median 19 mSv, p <
      0.001). Tube voltage, followed by tube current and the method of ECG
      synchronization were the strongest independent predictors of radiation dose.
      Growing experience with dose-saving techniques and CTA protocols tailored to the
      pediatric population have led to a tenfold reduction in radiation dose over
      recent years and now allow routinely performing ECG-synchronized CTA in children
      with a radiation dose on the order of 1 mSv. 

PMID- 25380964
TI  - Safety, efficacy and response to a hydrocortisone rescue therapy protocol in
      children with refractory hypotension after cardiopulmonal bypass.
AB  - Little is known about which paediatric patients respond to hydrocortisone rescue
      therapy (HRT) with improvement of haemodynamic stability in refractory
      hypotension after cardiopulmonal bypass. Data were gathered retrospectively from
      children who received HRT in refractory hypotension after cardiopulmonary bypass
      in the period from 2000 to 2010. One hundred and sixty-six out of 1,273 children,
      150 <1 year and 16 >1 year were enrolled. HRT improved haemodynamics
      significantly, increased blood pressure, decreased the vasoactive-inotropic score
      and plasma lactate concentrations in all children >1 year and in 82 % (123 out of
      150) of the infants <1 year. Non-responders <1 year were significantly younger,
      lighter, mostly male infants and had longer cardiopulmonary bypass support time.
      Serum lactate and paediatric risk of mortality score were significantly higher in
      non-responders at time of initiation of HRT. Mortality was significantly higher
      in non-responders versus responders (2.44 vs. 13.5 %; p = 0.0008). HRT caused no
      adverse effects like electrolyte disturbances or hyperglycaemia. HRT in
      refractory hypotension after paediatric cardiac surgery is safe but not all
      infants <1 year show haemodynamic response to HRT. Non-response to HRT is
      associated with significantly higher mortality. 

PMID- 25380965
TI  - A novel NKX2.6 mutation associated with congenital ventricular septal defect.
AB  - Congenital heart disease (CHD) is the most common birth defect and is the most
      prevalent non-infectious cause of infant death. Aggregating evidence demonstrates
      that genetic defects are involved in the pathogenesis of CHD. However, CHD is
      genetically heterogeneous and the genetic determinants for CHD in an overwhelming
      majority of patients remain unknown. In this study, the coding regions and splice
      junctions of the NKX2.6 gene, which encodes a homeodomain transcription factor
      crucial for cardiovascular development, were sequenced in 210 unrelated CHD
      patients. As a result, a novel heterozygous NKX2.6 mutation, p.K152Q, was
      identified in an index patient with ventricular septal defect (VSD). Genetic
      analysis of the proband's available family members showed that the mutation
      cosegregated with VSD transmitted as an autosomal dominant trait with complete
      penetrance. The missense mutation was absent in 400 control chromosomes and the
      altered amino acid was completely conserved evolutionarily across species. Due to
      unknown transcriptional targets of NKX2.6, the functional characteristics of the
      identified mutation at transcriptional activity were analyzed by using NKX2.5 as
      a surrogate. Alignment between human NKX2.6 and NKX2.5 proteins displayed that
      K152Q-mutant NKX2.6 was equivalent to K158Q-mutant NKX2.5, and introduction of
      K158Q into NKX2.5 significantly reduced its transcriptional activating function
      when compared with its wild-type counterpart. This study firstly links NKX2.6
      loss-of-function mutation with increased susceptibility to isolated VSD,
      providing novel insight into the molecular mechanism underpinning VSD and
      contributing to the development of new preventive and therapeutic strategies for
      this common form of CHD. 

PMID- 25380966
TI  - Early results of neurodevelopment following hybrid stage I for hypoplastic left
      heart syndrome.
AB  - Motor skills and neurodevelopment in infants with hypoplastic left heart syndrome
      (HLHS) who have undergone Hybrid Stage I palliation is unknown. The purpose of
      this study is to assess early neurodevelopment in infants with HLHS after Hybrid
      Stage I palliation. Developmental assessment was performed in HLHS infants who
      underwent Hybrid Stage I palliation at 2 and 4 months of age using the Test of
      Infant Motor Performance, and at 6 months of age, prior to undergoing the second
      staged surgery, using the Bayley Scales of Infant and Toddler Development, 3rd
      edition (Bayley-III). Results were compared to healthy control subjects and norm
      referenced data. The HLHS group scored between -1 and -2 standard deviations (SD)
      below the mean at 2 months of age (p = 0.002), and within -1 SD of the mean, at 4
      months of age (p = 0.0019), on the TIMP. Compared to the control group, composite
      motor skills were significantly lower at 6 months of age on the Bayley-III in the
      HLHS group (p = 0.0489), however, not significant for cognitive (p = 0.29) or
      language (p = 0.68). Percentile rank motor scores were 17 +/- 20 % in the HLHS
      group compared to 85 +/- 12 % for the healthy age-matched control group. Infants
      with HLHS who undergo Hybrid Stage I palliation score lower on standardized motor
      skill tests compared to healthy age-matched controls and the norm-referenced
      population. This suggests that infants with HLHS have poorer motor skill
      performance than typically developing infants at 6 months of age. 

PMID- 25380968
TI  - [Assessment of risk of bias in controlled studies].
AB  - BACKGROUND: Practicing physicians are faced with many medical decisions daily.
      These are mainly influenced by personal experience but should also consider
      patient preferences and the scientific evidence reflected by a constantly
      increasing number of medical publications and guidelines. With the objective of
      optimal medical treatment, the concept of evidence-based medicine is founded on
      these three aspects. It should be considered that there is a high risk of
      misinterpreting evidence, leading to medical errors and adverse effects without
      knowledge of the methodological background. OBJECTIVES: This article explains the
      concept of systematic error (bias) and its importance. Causes and effects as well
      as methods to minimize bias are discussed. This information should impart a
      deeper understanding, leading to a better assessment of studies and
      implementation of its recommendations in daily medical practice. CONCLUSION:
      Developed by the Cochrane Collaboration, the risk of bias (RoB) tool is an
      assessment instrument for the potential of bias in controlled trials. Good
      handling, short processing time, high transparency of judgements and a graphical
      presentation of findings that is easily comprehensible are among its strengths.
      Attached to this article the German translation of the RoB tool is published.
      This should facilitate the applicability for non-experts and moreover, support
      evidence-based medical decision-making.

PMID- 25380967
TI  - PDGF receptor alpha inhibition induces apoptosis in glioblastoma cancer stem
      cells refractory to anti-Notch and anti-EGFR treatment.
AB  - BACKGROUND: Cancer stem cells (CSC) represent a rare fraction of cancer cells
      characterized by resistance to chemotherapy and radiation, therefore nowadays
      there is great need to develop new targeted therapies for brain tumors and our
      study aim to target pivotal transmembrane receptors such as Notch, EGFR and
      PDGFR, which are already under investigation in clinical trials setting for the
      treatment of Glioblastoma Multiforme (GBM). METHODS: MTS assay was performed to
      evaluate cells response to pharmacological treatments. Quantitative RT-PCR and
      Western blots were performed to state the expression of Notch1, EGFR and
      PDGFRalpha/beta and the biological effects exerted by either single or combined
      targeted therapy in GBM CSC. GBM CSC invasive ability was tested in vitro in
      absence or presence of Notch and/or EGFR signaling inhibitors. RESULTS: In this
      study, we investigated gene expression and function of Notch1, EGFR and PDGFR to
      determine their role among GBM tumor core- (c-CSC) vs. peritumor tissue-derived
      cancer stem cells (p-CSC) of six cases of GBM. Notch inhibition significantly
      impaired cell growth of c-CSC compared to p-CSC pools, with no effects observed
      in cell cycle distribution, apoptosis and cell invasion assays. Instead, anti
      EGFR therapy induced cell cycle arrest, sometimes associated with apoptosis and
      reduction of cell invasiveness in GBM CSC. In two cases, c-CSC pools were more
      sensitive to simultaneous anti-Notch and anti-EGFR treatment than either therapy
      alone compared to p-CSC, which were mostly resistant to treatment. We reported
      the overexpression of PDGFRalpha and its up-regulation following anti-EGFR
      therapy in GBM p-CSC compared to c-CSC. RNA interference of PDGFRalpha
      significantly reduced cell proliferation rate of p-CSC, while its pharmacological
      inhibition with Crenolanib impaired survival of both CSC pools, whose effects in
      combination with EGFR inhibition were maximized. CONCLUSIONS: We have used
      different drugs combination to identify the more effective therapeutic targets
      for GBM CSC, particularly against GBM peritumor tissue-derived CSC, which are
      mostly resistant to treatments. Overall, our results provide the rationale for
      simultaneous targeting of EGFR and PDGFR, which would be beneficial in the
      treatment of GBM.

PMID- 25380969
TI  - Native kidney biopsies in Armenian and Swiss children: high prevalence of
      amyloidosis in Yerevan and of IgA nephropathy in Zurich.
AB  - The spectrum of pathology in native kidney biopsies varies considerably between
      different countries. Based on similar biopsy policy and joint workup, biopsy data
      of native kidneys of children in Yerevan (Armenia) and Zurich (Switzerland) were
      compared over a period of two decades (1993-2002 and 2003-2012). A total of 487
      renal biopsies in Yerevan (EVN), n = 253; median age 11.2 years (range 0.8-18; 56
      % males) and in Zurich (ZRH), n = 234; median age 8.7 years (range 0.1-18; 61 %
      males) were analyzed. Biopsies from EVN were locally analyzed by light microscopy
      (LM) and sent to ZRH for electron microscopy (EM) and immunohistochemistry.
      Biopsies from ZRH were evaluated by LM, EM, and immunofluorescence. The
      significant difference concerns the high frequency of amyloidosis in EVN (25.4 %
      in the first and 19.4 % in the second decade vs. 0 % in ZRH) and of IgA
      nephropathy in ZRH (30.2 % in the first and 26.1 % in the second decade vs. 8.1
      in EVN). Certain forms of glomerulonephritis (membranoproliferative type I and
      membranous) and primary focal segmental glomerulosclerosis tended to be more
      frequent in EVN than in ZRH. Amyloid nephropathy due to familial Mediterranean
      fever is still highly frequent in Armenia with a slight decrease in the second
      decade. In Switzerland, the most common finding was IgA nephropathy.

PMID- 25380970
TI  - Turkish version of the Anterior Cruciate Ligament Quality of Life questionnaire.
AB  - PURPOSE: To test the measurement properties of Turkish version of the Anterior
      Cruciate Ligament Quality of Life (ACL-QOL) questionnaire. METHODS: One hundred
      and nineteen patients with ACL reconstruction (ACL-R) completed internal
      consistency, agreement, construct validity, floor and ceiling effect analyses.
      Eighty out of 119 patients with ACL-R completed Turkish version of the ACL-QOL
      questionnaire twice for the test-retest reliability. A subgroup of thirty-nine
      patients undergoing physiotherapy were also asked to answer the ACL-QOL
      questionnaire, the Lysholm Knee Scale (LKS), Knee Outcome Survey-Activities of
      Daily Living Scale (KOS-ADLS) and the short form 36 (SF-36) at pre-operative,
      16th week and 2 years post-operatively to assess responsiveness. RESULTS: The
      questionnaire had high internal consistency (Cronbach's alpha = 0.95). The paired
      t test showed no significant difference between the test-retest means. The
      intraclass correlation was excellent for reliability and agreement in five
      domains and overall score (ICC 0.95, 0.95, 0.97, 0.95, 0.96 and 0.95; p < 0.001).
      The standard error of measurement and the minimum detectable change (MDC95) were
      found to be 3.1 points and 8.7 points, respectively. The questionnaire showed a
      fair correlation (r = 0.23) with LKS and a poor correlation (r = 0.14) with KOS
      ADLS; good and very good construct validity (r = 0.51, r = 0.62) with SF-36
      physical component score and mental component score, respectively. No ceiling and
      floor effects were observed except the subdomain of 'work-related concerns' (22.9
      %). A dramatic effect size was demonstrated at the 16th week (2.1) and 2 years
      (1.1) of follow-up. CONCLUSION: Turkish version of the ACL-QOL questionnaire is a
      reproducible and responsive instrument that can be used in clinical studies.
      LEVEL OF EVIDENCE: Diagnostic study, Level I.

PMID- 25380971
TI  - High-load preconditioning of soft tissue grafts: an in vitro biomechanical bovine
      tendon model.
AB  - PURPOSE: No consensus exists regarding the optimal preconditioning protocol that
      will minimize postoperative elongation while creating a graft that is
      biomechanically equivalent to the native anterior cruciate ligament (ACL). It was
      hypothesized that a preconditioning protocol of specific mode and magnitude would
      create a graft with equivalent stiffness to the native ACL. METHODS: Thirty-six
      bovine extensor tendon grafts were randomly allocated among six preconditioning
      groups (n = 6 per group) including three cyclic (10 cycles at 0.5 Hz between 10
      80, 100-300, and 300-600 N) and three static loading protocols (20 s at 80, 300,
      and 600 N). Grafts were then cyclically loaded between 50 and 250 N at 0.5 Hz for
      500 cycles to simulate an early rehabilitation protocol. RESULTS: Cyclic 300-600
      N and static 600 N loading protocols both demonstrated significantly less
      elongation during simulated rehabilitation when compared to lower, current
      clinical standard preconditioning levels of 10-80 N (-62% Delta) and 80 N (-69%
      Delta). The same high-load preconditioning protocols demonstrated statistical
      equivalence in stiffness when compared to the previously reported stiffness of
      the native ACL. CONCLUSIONS: In this experimental model, increased force applied
      to soft tissue grafts during preconditioning significantly decreased the
      subsequent elongation experienced during simulated early rehabilitation. A static
      load of 600 N removed the most graft elongation during preconditioning, had the
      least amount of cyclic displacement during simulated early rehabilitation, and
      was statistically equivalent to the native ACL stiffness. Implementation of high
      load preconditioning of soft tissue grafts may help improve outcomes following
      ACL reconstruction by reducing residual knee laxity resulting from postoperative
      graft elongation and the intrinsic viscoelastic properties of the graft tissue
      while imparting biomechanical characteristics (e.g. stiffness) equivalent to the
      native ACL.

PMID- 25380972
TI  - Intercondylar notch dimensions and graft failure after single- and double-bundle
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: The objective of this study was to evaluate the dimensions of the
      femoral intercondylar notch intraoperatively and to determine whether a small
      intercondylar notch increases the risk of graft failure after individualized
      anatomic single- or double-bundle anterior cruciate ligament (ACL)
      reconstruction. METHODS: A retrospective review of prospectively collected data
      was performed. One hundred and thirty-seven primary single- or double-bundle ACL
      reconstructions with at least 2-year follow-up were included in this study. Of
      these, 116 subjects had intraoperative notch measurements recorded. All
      operations were performed anatomically using a three-portal technique by the
      senior author. Intraoperative notch measurements (width at the base, middle, and
      top and height) were taken using a standard, commercially available arthroscopic
      ruler. Graft failure was defined as patient report of instability, pathologic
      laxity on clinical exam, or an MRI or arthroscopic diagnosis of rupture or
      absence of the ACL graft. RESULTS: Graft failure at 2-year follow-up in the
      overall population was 13.9 % (19/137). Graft failure was reported to occur from
      contact or non-contact trauma, failure of the graft to incorporate, or hardware
      failure. The dimensions of the intercondylar notch and the graft type used did
      not influence the risk of graft failure. CONCLUSIONS: Smaller intercondylar notch
      dimensions do not appear to be a risk factor for higher rates of graft failure
      after anatomic and individualized ACL reconstruction. Based on these data, the
      use of notchplasty is not supported in conjunction with individualized anatomic
      single- or double-bundle ACL reconstruction.

PMID- 25380973
TI  - Anatomic description of the anterolateral ligament of the knee.
AB  - PURPOSE: The anterolateral ligament, a structure that has been known for 130
      years, has again attracted the attention both of orthopaedic doctors and
      anatomists. Since its initial description until now, this structure has had
      different names. Whether labelled as the mid-third lateral capsular ligament, the
      anterior oblique band of the fibular collateral ligament or the anterolateral
      ligament of the knee, this structure has been responsible for the so-called
      Segond avulsion fractures. The aim of this study was to determine the precise
      position and layer of the lateral knee compartment within which the anterolateral
      ligament is located, as well as its type. METHODS: In this study, the anatomical
      dissection of the lateral segment of 14 cadaveric knees (six male, eight female;
      seven right, seven left; average age of subjects: 78 years) was performed. The
      dissection was carried out in keeping with Seebacher, layer by layer. RESULTS:
      The anterolateral ligament was identified in seven out of 14 cadaveric knee
      joints (50 %). The length of the ligament was 41 +/- 3 mm, while the width was 4
      +/- 1 mm and the thickness 1 mm (in the middle section). In 14 % of the cases,
      the anterior oblique band was identified as a part of the FCL. In all of the knee
      joints, a part of the fibres of the ITT with the same insertions and direction as
      the ALL was found, located, however, at a much more superficial level than the
      ALL. CONCLUSION: Analysis of the current scientific literature related to the
      anterolateral ligament and layer-by-layer dissection of the lateral region of 14
      cadaveric knees has led to the conclusion that the anterolateral ligament is a
      thickening of the knee joint capsule located in the third layer of the lateral
      region of the knee (according to Seebacher) which is not always clearly
      morphologically differentiated from the remainder of the joint capsule. The
      anterolateral ligament is unequivocally a part of the joint capsule, which is why
      any damage to it should be treated in the same way as any other damage to the
      joint capsule.

PMID- 25380974
TI  - Trophic level responses differ as climate warms in Ireland.
AB  - Effective ecosystem functioning relies on successful species interaction.
      However, this delicate balance may be disrupted if species do not respond to
      environmental change at a similar rate. Here we examine trends in the timing of
      spring phenophases of groups of species occupying three trophic levels as a
      potential indicator of ecosystem response to climate warming in Ireland. The data
      sets were of varying length (1976-2009) and from varying locations: (1) timing of
      leaf unfolding and May Shoot of a range of broadleaf and conifer tree species,
      (2) first appearance dates of a range of moth species, and (3) first arrival
      dates of a range of spring migrant birds. All three groups revealed a
      statistically significant (P<0.01 and P<0.001) advance in spring phenology that
      was driven by rising spring temperature (P<0.05; 0.45  degrees C /decade).
      However, the rate of advance was greater for moths (1.8 days/year), followed by
      birds (0.37 days/year) and trees (0.29 days/year). In addition, the length of
      time between (1) moth emergence and leaf unfolding and (2) moth emergence and
      bird arrival decreased significantly (P<0.05 and P<0.001, respectively),
      indicating a decrease in the timing between food supply and demand. These
      differing trophic level response rates demonstrate the potential for a mismatch
      in the timing of interdependent phenophases as temperatures rise. Even though
      these data were not specifically collected to examine climate warming impacts, we
      conclude that such data may be used as an early warning indicator and as a means
      to monitor the potential for future ecosystem disruption to occur as climate
      warms.

PMID- 25380975
TI  - Effects of shading on spike differentiation and grain yield formation of summer
      maize in the field.
AB  - A field experiment was conducted to study the effects of shading on tassel and
      ear development and yield formation of three summer maize hybrids Zhenjie 2
      (ZJ2), Denghai 605 (DH605), and Zhengdan 958 (ZD958). The ambient sunlight
      treatment was used as control (CK) and shading treatments (40 % of ambient
      sunlight) were applied at different growth stages from silking stage (R1) to
      physiological maturity stage (R6) (treatment S1), from the sixth extended leaf
      stage (V6) to R1 (treatment S2) and from seeding to R6 (treatment S3). Shading
      had no significant effect on the time from seeding to shoot emergence (VE);
      however, subsequent growth and development were delayed with shading beyond this
      point. The differentiation time of both tassel and ear delayed, and female spike
      (tassel) floret differentiation, sexual organ formation time, and anthesis
      silking interval (ASI) were lengthened. After shading, the total number of
      floret, silk, and fertilization floret reduced significantly; the number of
      abortive seeds increased, and the total setting percentage among different
      treatments showed that CK>S2>S1>S3; and the total setting percentages in S1, S2,
      and S3 of ZD958 were 44, 72, and 15 % respectively. The total floret number of
      tassel primordium differentiation, fertility rate, and seed setting rate of
      florets in S3 treatment was the minimum; kernels per ear decreased seriously and
      single ear setting percentage was only 16 %; although floret degeneration number
      of S2 during ear differentiation stages increased and floret fertility rate
      reduced than that of CK, fertilization flower seed production increased and
      abortive seed decreased after canceling shading. Aborted kernel of S1 increased
      and kernel dry weight reduced, resulting in a significant decrease of kernel
      number per ear and kernel weight, and the grain abortive rate of 40-62 %. In
      conclusion, shading changed the growth and development process and caused
      infertility of tassel and ear; tassel branches decreased, reducing pollen
      vitality and silks differentiation cut down; and grain dry matter accumulation
      and setting percentage decreased, causing yield reduction. Grain yield and
      biomass reduced 66, 36, and 93 % compared to the control by shading treatments of
      S1, S2, and S3, respectively.

PMID- 25380977
TI  - A review on the efficacy and safety of gabapentin in the treatment of chronic
      cough.
AB  - INTRODUCTION: Effective antitussives available to control cough are limited.
      Consolidation among different afferent branches of the vagus nerve is needed to
      bring about cough. A general, widely accepted view is that the chronic increase
      in the sensitivity of the cough reflex is associated with inflammatory
      hypersensitivity such as from gastro-esophageal reflux disease. There is
      increasing evidence that an important mechanism is a sensory disorder of the
      laryngeal branches of the vagus nerve. Neuromodulating drugs are effectively used
      in the treatment of chronic pain and neuropathic disorders and may have a role in
      the treatment of refractory chronic cough (CC). AREAS COVERED: Current evidence
      on the efficacy and safety of gabapentin in the treatment of CC is reviewed.
      Relevant randomized controlled trials, case reports and reviews were identified
      through a PubMed search of English-language literature referring to cough,
      sensory neuropathy and gabapentin over the last 10 years. EXPERT OPINION:
      Gabapentin appears to be effective and well tolerated in the treatment of CC and
      in other sensory neuropathic disorders. Relevant clinical trials investigating
      its efficacy and safety profile in the treatment of cough are limited and further
      studies are needed. Gabapentin has been shown to cause minimal to no toxicity in
      overdose.

PMID- 25380979
TI  - Transsaccadic processing: stability, integration, and the potential role of
      remapping.
AB  - While our frequent saccades allow us to sample the complex visual environment in
      a highly efficient manner, they also raise certain challenges for interpreting
      and acting upon visual input. In the present, selective review, we discuss key
      findings from the domains of cognitive psychology, visual perception, and
      neuroscience concerning two such challenges: (1) maintaining the phenomenal
      experience of visual stability despite our rapidly shifting gaze, and (2)
      integrating visual information across discrete fixations. In the first two
      sections of the article, we focus primarily on behavioral findings. Next, we
      examine the possibility that a neural phenomenon known as predictive remapping
      may provide an explanation for aspects of transsaccadic processing. In this
      section of the article, we delineate and critically evaluate multiple proposals
      about the potential role of predictive remapping in light of both theoretical
      principles and empirical findings. 

PMID- 25380978
TI  - Sex differences in the effects of residential treatment on the quality of life of
      eating disorder patients.
AB  - AIMS: This study compared the effects of residential treatment on improving
      health-related quality of life (HRQOL) between males and females diagnosed with
      eating disorders (EDs) from admission to discharge and at follow-up. This study
      also analyzed the association between changes in HRQOL and changes in the
      severity of ED pathology, depression, and trait anxiety. METHODS: 145 consecutive
      patients (34 males and 111 females) admitted to a residential ED unit completed a
      panel of surveys at admission and discharge. The survey panel included the Eating
      Disorders Quality of Life Survey (EDQLS), the Eating Disorder Examination
      Questionnaire, the Quick Inventory of Depressive Symptomatology and the State
      Trait Anxiety Inventory. An online follow-up survey was also conducted for the
      EDQLS. Mixed-factorial ANOVA was used to examine sex differences and changes in
      HRQOL between admission, discharge and post-treatment follow-up. Multiple
      regression analysis was used to investigate the relationship between sex, change
      in HRQOL, and changes in all other variables studied. RESULTS: By the end of
      residential treatment, both males and females had made similar statistically
      significant improvements in HRQOL from admission to discharge, which persisted
      after treatment. Greater decreases in ED pathology and trait anxiety
      significantly predicted greater increases in HRQOL during residential treatment
      while sex and changes in depression did not. CONCLUSION: The data show that
      residential treatment is an effective approach to improving HRQOL in both males
      and females with EDs. Greater improvements in trait anxiety and ED pathology
      contributed to greater improvement in HRQOL in these patients.

PMID- 25380980
TI  - Transcriptional responses of PBMC in psychosocially stressed animals indicate an
      alerting of the immune system in female but not in castrated male pigs.
AB  - BACKGROUND: Brain and immune system are linked in a bi-directional manner. To
      date, it remained largely unknown why immune components become suppressed,
      enhanced, or remain unaffected in relation to psychosocial stress. Therefore, we
      mixed unfamiliar pigs with different levels of aggressiveness. We separated
      castrated male and female pigs into psychosocially high- and low- stressed
      animals by skin lesions, plasma cortisol level, and creatine kinase activity
      obtained from agonistic behaviour associated with regrouping. Peripheral blood
      mononuclear cells (PBMC) were collected post-mortem and differential gene
      expression was assessed using the Affymetrix platform (n = 16). RESULTS: Relevant
      stress-dependent alterations were found only between female samples, but not
      between castrated male samples. Molecular routes related to TREM 1 signalling,
      dendritic cell maturation, IL-6 signalling, Toll-like receptor signalling, and IL
      8 signalling were increased in high stressed females compared to low stressed
      females. This indicates a launch of immune effector molecules as a direct
      response. According to the shifts of transcripts encoding cell surface receptors
      (e.g. CD14, TLR2, TLR4, TREM1) the study highlights processes acting on pattern
      recognition, inflammation, and cell-cell communication. CONCLUSIONS: The
      transcriptional response partly affected the degree of 'stress responsiveness',
      indicating that the high stressed females altered their signal transduction due
      to potential infections and injuries while fighting.

PMID- 25380982
TI  - Synthesis and evaluation of anticancer activity in cells of novel stoichiometric
      pegylated fullerene-doxorubicin conjugates.
AB  - PURPOSE: To synthesize pegylated stoichiometrically and structurally well-defined
      conjugates of fullerene (C60) with doxorubicin (DOX) and investigate their
      antiproliferative effect against cancer cell lines. METHODS: Stoichiometric (1:1
      and 1:2) pegylated conjugates of C60 with DOX were synthesized using the Prato
      reaction to create fulleropyrrolidines equipped with a carboxyl function for
      anchoring a polyethylene glycol (PEG) moiety and either a hydroxyl group for
      attaching one molecule of DOX or a terminal alkyne group for attaching two
      molecules of DOX through a click reaction. In both conjugates, the DOX moieties
      are held through a urethane-type bond. Drug release was studied in phosphate
      buffer (PBS, pH 7.4) and MCF-7 cancer cells lysate. The uptake of the conjugates
      by MCF-7 cancer cells and their intracellular localization were studied with
      fluorescence microscopy. The antiproliferative activity of the conjugates was
      investigated using the WST-1 test. RESULTS: One or two DOX molecules were
      anchored on pegylated C60 particles to form DOX-C60-PEG conjugates. Drug
      liberation from the conjugates was significantly accelerated in the presence of
      tumor cell lysate compared to PBS. The conjugates could be internalized by MCF-7
      cells. DOX from the conjugates exhibited much delayed, compared to free DOX,
      localization in the nucleus and antiproliferative activity. CONCLUSION: Pegylated
      DOX-C60 conjugates (1:1) and (2:1) with well-defined structure were successfully
      synthesized and found to exhibit comparable, but with a delayed onset,
      antiproliferative activity with free DOX against MCF-7 cancer cells. The results
      obtained justify further investigation of the potential of these conjugates as
      anticancer nanomedicines.

PMID- 25380981
TI  - Evaluation of the usefulness of breast cancer resistance protein (BCRP) knockout
      mice and BCRP inhibitor-treated monkeys to estimate the clinical impact of BCRP
      modulation on the pharmacokinetics of BCRP substrates.
AB  - PURPOSE: To evaluate whether the impact of functional modulation of the breast
      cancer resistance protein (BCRP, ABCG2 421C>A) on human pharmacokinetics after
      oral administration is predictable using Bcrp knockout mice and cynomolgus
      monkeys pretreated with a BCRP inhibitor, elacridar. METHODS: The correlation of
      the changes of the area under the plasma concentration-time curve (AUC) caused by
      ABCG2 421C>A with those caused by the Bcrp knockout in mice, or BCRP inhibition
      in monkeys, was investigated using well-known BCRP substrates (rosuvastatin,
      pitavastatin, fluvastatin, and sulfasalazine). RESULTS: In mice, the
      bioavailability changes, which corrected the effect of systemic clearance by Bcrp
      knockout, correlated well with the AUC changes in humans, whereas the correlation
      was weak when AUC changes were directly compared. In monkeys, the AUC changes
      pretreated with elacridar resulted in a good estimation of those in humans within
      approximately 2-fold ranges. CONCLUSIONS: This study suggests that
      pharmacokinetics studies that use the correction of the bioavailability changes
      in Bcrp knockout mice are effective for estimating clinical AUC changes in ABCG2
      421C>A variants for BCRP substrate drugs and those studies in monkeys that use a
      BCRP inhibitor serve for the assessment of BCRP impact on the gastrointestinal
      absorption in a non-rodent model.

PMID- 25380983
TI  - Initial studies on the direct and modulatory effects of nitric oxide on an
      identified central Helix aspersa neuron.
AB  - The generation of the novel messenger molecule nitric oxide (NO) has been
      demonstrated in many tissues across phyla including nervous systems. It is
      produced on demand by the enzyme nitric oxide synthase often stimulated by
      intracellular calcium and typically affecting guanylate cyclase thought to be its
      principal target in an auto and/or paracrine fashion. This results in the
      generation of the secondary messenger cyclic guanosine monophosphate (cGMP).
      Nitric oxide synthase has been demonstrated in various mollusk brains and
      manipulation of NO levels has been shown to affect behavior in mollusks. Apart
      from modulation of the effect of the peptide GSPYFVamide, there appears little
      published on direct or modulatory effects of NO on Helix aspersa central neurons.
      We present here initial results to show that NO can be generated in the region
      around F1 in the right parietal ganglion and that NO and cGMP directly
      hyperpolarize this neuron. For example, application of the NO-donor S-nitroso-N
      acetyl-D,L-penicillamine (SNAP; 200 uM) can cause a mean hyperpolarization of
      41.7 mV, while 2 mM 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP)
      produced a mean hyperpolarization of 33.4 mV. Additionally, pre-exposure to NO
      donors or cGMP appears to significantly reduce or even eliminates the normal
      hyperpolarizing K(+)-mediated response to dopamine (DA) by this neuron; 200 uM
      SNAP abolishes a standard response to 0.5 uM DA while 1 mM 8-bromo-cGMP reduces
      it 62%.

PMID- 25380984
TI  - Stochastic parameter search for events.
AB  - BACKGROUND: With recent increase in affordability and accessibility of high
      performance computing (HPC), the use of large stochastic models has become
      increasingly popular for its ability to accurately mimic the behavior of the
      represented biochemical system. One important application of such models is to
      predict parameter configurations that yield an event of scientific significance.
      Due to the high computational requirements of Monte Carlo simulations and
      dimensionality of parameter space, brute force search is computationally
      infeasible for most large models. RESULTS: We have developed a novel parameter
      estimation algorithm-Stochastic Parameter Search for Events (SParSE)-that
      automatically computes parameter configurations for propagating the system to
      produce an event of interest at a user-specified success rate and error
      tolerance. Our method is highly automated and parallelizable. In addition,
      computational complexity does not scale linearly with the number of unknown
      parameters; all reaction rate parameters are updated concurrently at the end of
      each iteration in SParSE. We apply SParSE to three systems of increasing
      complexity: birth-death, reversible isomerization, and Susceptible-Infectious
      Recovered-Susceptible (SIRS) disease transmission. Our results demonstrate that
      SParSE substantially accelerates computation of the parametric solution
      hyperplane compared to uniform random search. We also show that the novel
      heuristic for handling over-perturbing parameter sets enables SParSE to compute
      biasing parameters for a class of rare events that is not amenable to current
      algorithms that are based on importance sampling. CONCLUSIONS: SParSE provides a
      novel, efficient, event-oriented parameter estimation method for computing
      parametric configurations that can be readily applied to any stochastic systems
      obeying chemical master equation (CME). Its usability and utility do not diminish
      with large systems as the algorithmic complexity for a given system is
      independent of the number of unknown reaction rate parameters.

PMID- 25380985
TI  - Efficient differentiation of human embryonic stem cells toward dopaminergic
      neurons using recombinant LMX1A factor.
AB  - Direct differentiation of dopaminergic (DA) neurons from human pluripotent stem
      cells (hPSCs) in the absence of gene manipulation is the most desired alternative
      to clinical treatment of Parkinson disease. Protein transduction-based methods
      could be efficient, safe approaches to enhance direct differentiation of human
      embryonic stem cells (hESCs) to DA neurons. In the present study, we compared the
      differentiation efficiency of DA neurons from hESCs with and without the
      application of LIM homeobox transcription factor 1 alpha (LMX1A), a master
      regulatory protein in the development of the midbrain neurons and SHH proteins.
      The results obtained revealed that the treatment of hESCs with recombinant LMX1A
      (rLMX1A) protein along with dual SMAD inhibition led to higher expression of
      LMX1B, LMX1A, FOXA2, PITX3, EN1, and WNT1 effector endogenous genes and two-fold
      expression of PITX3. Moreover, the highest expression level of PITX3 and TH was
      observed when rLMX1A was added to the induction medium supplemented with SHH. To
      our best knowledge, this is the first report demonstrating the application of TAT
      LMX1A recombinant protein to enhance hESC differentiation to DA as shown by the
      expression of DA specific makers. These findings pave the way for enhancing the
      differentiation of hESCs to DA neurons safely and efficiently without genetic
      modification.

PMID- 25380986
TI  - Cloning, expression, and purification of a synthetic human growth hormone in
      Escherichia coli using response surface methodology.
AB  - The aim of this study was to achieve high-level production of the human growth
      hormone (hGH) in the prokaryotic expression system. In this regard, we performed
      cloning, expression, and purification of a synthetic hGH gene in BL21 (DE3)
      strain of E. coli. The hGH production was determined by SDS-PAGE and western
      blotting techniques, and then the protein concentration was determined by the
      Bradford assay. To gain insight into the effect of different nutrients on the
      growth of E. coli and hGH production, in a preliminary assessment nine different
      types of the basal medium were analyzed. The highest growth of E. coli and hGH
      production were observed in TB and SOB media. Accordingly, design of experiments
      was employed for screening the most significant nutrients, and central composite
      face design was applied for the optimization. The optimum medium consisted of
      yeast extract (10 g/L), tryptone (10 g/L), and K2HPO4 (2 g/L). The optimum hGH
      concentration was 391 mg/L, which was 3-fold higher than the hGH concentration in
      the LB basal medium (119 mg/L). This production rate is the highest hGH
      concentration reported in the IPTG-inducible expression systems.

PMID- 25380987
TI  - Zibibbo nero characterization, a red-wine grape revertant of muscat of
      Alexandria.
AB  - Muscat of Alexandria is known in Italy as Zibibbo. Zibibbo nero, red-wine grapes,
      is a sport mutation of Zibibbo variety. A biochemical and molecular
      characterization of berry colour (VvMybA1 and VvMybA2 genes, Vitis vinifera
      MYeloBlastosis) and aroma Muscat (VvDXS gene, 1-deoxy-D-xylulose 5-phosphate
      synthase) traits in both Zibibbo cultivars was performed, as well as
      ampelographic and genetic identification analyses. Molecular investigations were
      performed also for two putative Zibibbo parents (Moscato Bianco and Triboto), in
      order to prove the white-to-red shift of the red-skinned mutant. Ampelographic
      and genetic analysis demonstrated the high similarity between Zibibbo and Zibibbo
      nero, as well as a comparable aroma profile, characterized mainly by high content
      of linalool, geranic acid and geraniol (about 70 %). The Zibibbo nero anthocyanin
      profile was characterized by a high proportion in cyanidin-3-O-glucoside (about
      69.23 %). The molecular characterization of VvMybA1 and VvMybA2 locus detected
      non-functional alleles for white-skinned samples, while also the functional
      alleles were observed for red-skinned samples. About the VvDXS locus, the
      aromatic varieties showed the typical pattern of Muscat variety, while Triboto
      (Zibibbo parent) showed the non-Muscat-like flavour pattern. The colour locus
      structure of Zibibbo and its putative parents suggested that Zibibbo nero is a
      berry colour revertant of Zibibbo.

PMID- 25380988
TI  - Valorization of genetic variability for the qualitative improvement of
      autochthonous grape cultivars of Ciro's terroir through the self-fertilization.
AB  - This study uses PCR-derived marker systems to investigate the genetic differences
      of 22 grapevine accessions obtained through a self-fertilization program using
      Gaglioppo and Magliocco dolce. The aim of the study was to improve some
      qualitative parameters, while preserving the adaptive characteristics of these
      two cultivars to the adverse environmental conditions of the Calabria region
      (southern Italy). These two Calabrian grapevines have been cultivated within a
      restricted area and have been placed under a strong anthropic pressure which has
      limited their phenotypical variability with no selection of higher performant
      biotypes. Therefore, to have accessions with improved qualitative traits, a
      program of genetic improvement based on the self-fertilization of Gaglioppo and
      Magliocco dolce cultivars was performed in 1998, producing 3,122 accessions.
      Selection cycles were performed in 14 years. A first selection cycle (1998-2000),
      based on visual inspection of vegetative traits, selected 1,320 accessions,
      planted in an experimental vineyard in 2000. A second selection cycle (2000
      2008), based on phenotypic traits, sanitary aspects, and chemical composition of
      the grapes, selected 42 accessions, planted in a new experimental vineyard in
      2008. A final selection cycle (2008-2012), produced 22 accessions (virus free),
      with the best agronomic, sanitary, and qualitative aspects: two accessions
      obtained from Gaglioppo have been selected by color characteristics (i.e.,
      anthocyanin total content and stability); 20 genotypes obtained from Magliocco
      dolce had a better macro-composition of the grape (i.e., good sugar content with
      a balanced acidity). SSR analyses were performed to check the self-fertilization
      process. The study of genetic differences between accessions was performed by
      AFLPs, SAMPLs, and M-AFLPs. The application of the above-mentioned techniques
      allowed both to discriminate molecularly the 22 accessions grouped these
      accessions according to their genetic similarity. The self-fertilization approach
      has enabled improvement in the quality of the grapes, while preserving the high
      degree of adaptation to the environment of these two native Calabrian cultivars
      in southern Italy.

PMID- 25380989
TI  - Prognostic significance of the progesterone receptor status in Ki67-high and -low
      Luminal B-like HER2-negative breast cancers.
AB  - BACKGROUND: Breast cancer is a heterogeneous disease, and immunohistochemical
      evaluation is a surrogate marker that is widely used in clinical settings to
      identify the intrinsic subtypes. The definition of the Luminal B-like breast
      cancer was changed at the 2013 St. Gallen meeting; therefore, we investigated the
      clinicopathological features of the new Luminal B-like breast cancer categorized
      in the latest definition. We also compared the conventional PgR-high Luminal B
      like breast cancer with the conventional PgR-low or -negative Luminal B-like
      breast cancer. PATIENTS: We investigated 118 Luminal HER2-negative breast cancer
      patients who were operated in 2005-2008 at a single institution. Data on each
      patient's medical history were retrieved. RESULTS: A subset of patients (14.4 %)
      was categorized as the new Luminal B-like due to low or negative PgR: 58.8 % were
      histological grade I, 65 % were T1 in tumor size, and half had node involvement.
      Chemotherapy was performed in half of the cases. Breast cancer-related events
      were more frequent for the new Luminal B-like breast cancer than for the Luminal
      A-like breast cancer and were less frequent than for the conventional Luminal B
      like breast cancer. Based on multivariate analysis, low or negative expression of
      PgR and the absence of hormonal therapy were worse prognostic factors. When
      categorized into two groups by the PgR status, 48.1 % of the conventional Luminal
      B-like breast cancer was PgR-high; tumor size was smaller, and nodal involvement
      was less in this group. The rate of adjuvant chemotherapy of the conventional PgR
      high Luminal B-like breast cancer was less than that of the conventional PgR-low
      or -negative Luminal B-like breast cancer. Breast cancer-related events were
      significantly lower in the conventional PgR-high Luminal B-like breast cancer.
      CONCLUSIONS: Our results show the possibility that PgR status has some influence
      on the prognosis for Luminal HER2-negative breast cancers. Therefore, attention
      should be paid to the PgR status as well as Ki-67.

PMID- 25380990
TI  - Importance of work-life balance among German medical students who wish to become
      gynecologists.

PMID- 25380991
TI  - Reactivity of hexanuclear ruthenium metallaprisms towards nucleotides and a DNA
      decamer.
AB  - The reactivity of three hexacationic arene ruthenium metallaprisms towards
      isolated nucleotides and a short DNA strand was investigated using NMR
      spectroscopy, ESI mass spectrometry, UV/Vis and circular dichroism spectroscopy.
      The metallaprism built from oxalato-bridging ligands reacts rapidly in the
      presence of deoxyguanosine monophosphate (dGMP) and deoxyadenosine monophosphate,
      while the benzoquinonato derivative only reacts with dGMP. On the other hand, the
      larger metallaprism incorporating naphtoquinonato bridges remains stable in the
      presence of nucleotides. The reactivity of the three hexacationic metallaprisms
      with the decameric oligonucleotide d(CGCGATCGCG)2 was also investigated. Analysis
      of the NMR, MS, UV/Vis and CD data suggests that no adducts are formed between
      the oligonucleotide and the metallaprisms, but electrostatic interactions,
      leading to partial unwinding of the double-stranded oligonucleotide, were
      evidenced. 

PMID- 25380992
TI  - Do defensive chemicals facilitate intraguild predation and influence invasion
      success in ladybird beetles?
AB  - Egg predation and cannibalism are believed to be common phenomena among many
      species of aphidophagous predatory ladybird beetles despite the presence of
      alkaloid based defensive chemicals in all life stages. We identified defensive
      chemicals from eggs of three congeneric species, one introduced into North
      America (Coccinella septempunctata L.), and two native (C. transversoguttata
      richardsoni Brown, and C. novemnotata Herbst), and examined the effects of
      ingested defensive chemicals on first instars. Ingested congeneric alkaloids were
      not toxic to first instars, likely because the three congeners produce the same
      principal alkaloids, precoccinelline and coccinelline, in similar amounts. First
      instars of the three congeners accumulated alkaloids ingested through egg
      cannibalism and congeneric predation. Egg consumption doubled the amount of
      alkaloids in first instars when they fed on conspecific or congeneric eggs, in
      comparison to a pea aphid diet. No detrimental effects of ingested congeneric
      alkaloids on development or survival of first instars were observed among these
      congeners. Chemical defenses of eggs are therefore not likely to be important in
      favoring the invasive species, C. septempunctata, in interactions with these
      native congeneric species. Because the invasive species is the most aggressive
      predator, having the same types of alkaloids may facilitate disproportionate
      intraguild predation on native congeners by C. septempunctata thereby potentially
      enhancing the invasion success of this introduced species. 

PMID- 25380993
TI  - Attractiveness of harlequin bug, Murgantia histrionica, aggregation pheromone:
      field response to isomers, ratios, and dose.
AB  - A two-component pheromone, (3S,6S,7R,10S)- and (3S,6S,7R,10R)-10,11-epoxy-1
      bisabolen-3-ol (murgantiol), present in emissions from adult male harlequin bugs,
      Murgantia histrionica, is most attractive in field bioassays to adults and nymphs
      in the naturally occurring ratio of ca. 1.4:1. Each of the two individual
      synthetic stereoisomers is highly attractive to male and female adults and
      nymphs, but is more attractive in combination and when deployed with a harlequin
      bug host plant. Blends of 8 stereoisomers also are highly attractive, suggesting
      that isomers not found in the natural pheromone are not repellent. Deployment of
      an inexpensive non-stereospecific synthetic pheromone holds promise for efficient
      trapping and/or use in trap-crops for this important pest in North America. 

PMID- 25380995
TI  - Activated partial thromboplastin time sensitivity to lupus anticoagulant in a
      patient with transient arthritis and lupus anticoagulant-hypoprothrombinemia
      syndrome.

PMID- 25380994
TI  - The Nkateko health service trial to improve hypertension management in rural
      South Africa: study protocol for a randomised controlled trial.
AB  - BACKGROUND: South Africa has a high and rising prevalence of hypertension. Many
      affected individuals are not using medication, and few have controlled blood
      pressure. Until recently, primary care clinics focused on maternal and child
      health and management of acute conditions, but new government initiatives have
      shifted the focus to chronic diseases, including HIV/AIDS and hypertension.
      METHODS/DESIGN: The Nkateko trial will test the effectiveness of clinic-based lay
      health workers (LHWs) in supporting hypertension management. It is a pragmatic,
      cluster randomised controlled trial based in the Agincourt subdistrict of
      northeast South Africa, and it is underpinned by long-term health and demographic
      surveillance. Eight primary care facilities, with their catchment communities,
      are randomised to usual care or the addition of LHWs focused on chronic care. All
      clinics (intervention and control) will be provided with a clerk to collect
      information on clinic attendees and will match them to preexisting surveillance
      records. Intervention clinics will have LHWs working alongside nursing staff and
      focusing on health care for people with chronic conditions, particularly
      hypertension. The LHWs will be supported by an implementation manager, who will
      work with clinic staff to develop the most effective role for the LHWs. Control
      clinics will continue to provide usual care. The primary outcome will be the
      change between two population surveys conducted before and after the intervention
      in the proportion of the population with uncontrolled hypertension and a risk
      profile indicating at least moderate risk of cardiovascular disease. A process
      evaluation will be based on a realist approach using patient exit interviews,
      clinic observations and interviews with health professionals, LHWs and patients
      to document the intervention and its implementation. DISCUSSION: There are
      challenges in the design of this trial. Assessing change through population
      surveys may reduce measurable effects; however, we feel this is appropriate
      because we aim to attract those who currently do not use clinics, and we hope to
      improve care for clinic users. Clinics were randomised at an open meeting because
      we were concerned that a remote process of randomisation would not be trusted by
      the community. We are constantly working to achieve an effective balance between
      the intervention and process evaluations. TRIAL REGISTRATION: ISRCTN12128227
      (registered 5 March 2014).

PMID- 25380996
TI  - Erlotinib is not effective in patients with JAK2V617F-positive polycythemia vera.

PMID- 25380997
TI  - Nonspecific interstitial pneumonia: clinical associations and outcomes.
AB  - BACKGROUND: Studies have shown that nonspecific interstitial pneumonitis (NSIP),
      even when initially diagnosed as an idiopathic form of the disease, might be
      associated with an autoimmune background that later reveals itself as an organ
      specific or a systemic autoimmune disease. METHODS: NSIP patients were divided
      into three groups. The NSIP patients who met the criteria for having a systemic
      autoimmune disease (SAD) were defined as the systemic autoimmune disease
      associated NSIP (SAD-NSIP) group. The NSIP patients who did not meet the criteria
      for a systemic autoimmune disease were defined as an antibody-positive group (i
      NSIP-Ab + group) if their sera were positive for autoantibodies. The NSIP
      patients with negative serologic tests for auto-antibodies were defined as the
      antibody-negative group (i-NSIP-Ab- group). The clinical characteristics were
      analyzed and compared among the three groups. RESULTS: Ninety-seven NSIP patients
      were included. The mean age of the study population was 48 +/- 11 years. The mean
      follow-up time was 54 +/- 34 months. At the time of the surgical lung biopsies,
      23/97 (23.7%) of the patients were classified as SAD-NSIP; 30/97 (30.9%) were in
      the i-NSIP-Ab + group; and 44/97 (45.4%) were in the i-NSIP-Ab- group. At the end
      of the follow-up period, three cases were diagnosed with polymyositis (one case
      from the i-NSIP-Ab + group, two cases from the i-NSIP-Ab- group), one with
      scleroderma (from the i-NSIP-Ab + group, scl-70 positive and skin biopsy) and
      another one with microscopic polyarteritis (from the i-NSIP-AB-group, p-ANCA and
      MPO positive, renal biopsy). Three cases in the i-NSIP-Ab- group were later found
      to be positive for autoantibodies. Due to these changes in classification, at the
      end of the follow-up period, the SAD-NSIP group consisted of 28/97 patients
      (28.9%), the i-NSIP-Ab + group of 31/97 (32.0%) and the i-NSIP-Ab- group of
      38/97(39.1%). There were no significant differences in clinical manifestations,
      radiographic findings or pulmonary function tests among the three groups at the
      time of surgical lung biopsy or after reclassification after the follow-up
      period. SAD was an independent risk factor for the survival of the patients with
      NSIP after follow-up. CONCLUSION: Follow-up is recommended because idiopathic
      NSIP may be the first manifestation of a systemic autoimmune disease.

PMID- 25380998
TI  - Apolipoprotein C3 genetic polymorphisms are associated with lipids and coronary
      artery disease in a Chinese population.
AB  - BACKGROUND: The disorder of triglyceride (TG) metabolism leading to
      hypertriglyceridemia is an independent risk factor for coronary artery disease
      (CAD). Variants in the apolipoprotein C3 (APOC3) gene were found to be associated
      with elevated TG levels. The purpose of this study was to investigate the effect
      of two polymorphisms (1100 C/T and 3238 C/G) of APOC3 on plasma lipid and risk of
      CAD in a Chinese population. METHODS: The study population consisted of 600
      patients with CAD and 600 age- and gender-matched controls. The APOC3 gene
      polymorphism was analyzed using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). RESULTS: Patients with CAD had a significantly
      higher frequency of APOC3 3238 GG genotype [odds ratio (OR) =1.64, 95% confidence
      interval (CI) =1.10, 2.43; P = 0.01] and APOC3 3238 G allele (OR =1.27, 95% CI
      =1.04, 1.55; P = 0.02) than controls. The findings are still emphatic by the
      Bonferroni correction. When stratifying by hyperlipidemia, CAD patients with
      hyperlipidemia had a significantly higher frequency of APOC3 3238 GG genotype (OR
      =1.73, 95% CI =1.13, 2.64; P = 0.01) than without hyperlipidemia. The APOC3 3238
      G allele was significantly associated with increasing plasma TG levels and very
      low-density lipoprotein cholesterol (VLDL-C) levels both in cases and controls (P
      < 0.001). CONCLUSIONS: The APOC3 3238 G allele might contribute to an increased
      risk of CAD as a result of its effect on TG and VLDL-C metabolism.

PMID- 25380999
TI  - Radiation dose from multidetector CT studies in children: results from the first
      Italian nationwide survey.
AB  - BACKGROUND: Multidetector CT (MDCT) scanners have contributed to the widespread
      use of CT in paediatric imaging. However, concerns are raised for the associated
      radiation exposure. Very few surveys on radiation exposure from MDCT studies in
      children are available. OBJECTIVE: The aim of this study was to outline the
      status of radiation exposure in children from MDCT practice in Italy. MATERIALS
      AND METHODS: In this retrospective multicentre study we asked Italian radiology
      units with an MDCT scanner with at least 16 slices to provide dosimetric and
      acquisition parameters of CT examinations in three age groups (1-5, 6-10, 11-15
      years) for studies of head, chest and abdomen. The dosimetric results were
      reported in terms of third-quartile volumetric CT dose index (CTDIvol) (mGy),
      size-specific dose estimate (SSDE) (mGy), dose length product (DLP) (mGy cm), and
      total DLP for multiphase studies. These results were compared with paediatric
      European and adult Italian published data. A multivariate analysis assessed the
      association of CTDIvol with patient characteristics and scanning modalities.
      RESULTS: We collected data from 993 MDCT examinations performed at 25 centres.
      For age groups 1-5 years, 6-10 years and 11-15 years, the CTDIvol, DLP and total
      DLP values were statistically significantly below the values observed in our
      analogous national survey in adults, although the difference decreased with
      increasing age. CTDIvol variability among centres was statistically significant
      (variance = 0.07; 95% confidence interval = 0.03-0.16; P < 0.001). CONCLUSIONS:
      This study reviewed practice in Italian centres performing paediatric imaging
      with MDCT scanners. The variability of doses among centres suggests that the use
      of standardised CT protocols should be encouraged.

PMID- 25381000
TI  - Orbital lymphomatoid granulomatosis - a rare cause of proptosis.
AB  - A 1-year-old girl with unilateral proptosis was found to have primary orbital
      lymphomatoid granulomatosis - a condition rarely occurring in children. This
      multisystem angiocentric, angiodestructive, lymphoproliferative disease typically
      involves the lungs, with ocular involvement being extremely uncommon. Our case
      serves to illustrate the imaging findings of this unusual condition and highlight
      a rare cause of proptosis. 

PMID- 25381001
TI  - Finding Order in Chaos: A Review of Hospital Ratings.
AB  - Publicly reported hospital performance data have become widely available to
      health care consumers in recent years. In response to a growing demand for more
      readily available health care information, various organizations have begun
      assessing hospital performance. These performance reporting systems have
      tremendous potential to aid patients, families, and primary care providers in
      their clinical decision making. This study takes a systematic approach to review
      the main features of 9 existing hospital rating systems, each of which is
      described using 9 areas of evaluation. The hospital rating systems included in
      this study vary widely in scope, methodology, transparency, and presentation of
      their results. Their results often present conflicting conclusions regarding the
      performance of the same hospital. This review of hospital rating systems
      demonstrates how public reporting may add confusion to patients' health care
      decision making. 

PMID- 25381002
TI  - Health Disparities: Will a Coalition of the Willing Make a Difference?

PMID- 25381003
TI  - Clinical Quality Improvement Curriculum for Faculty in an Academic Medical
      Center.
AB  - Interested faculty enrolled in this 6-month-long quality improvement (QI) course
      to facilitate independent QI project work. The course included monthly 1.5-hour
      sessions: 20-minute presentations covering key QI concepts, then small group
      activities to facilitate project work. Faculty were required to identify,
      construct, and implement an independent QI project. They met individually with
      mentors twice during the course, with additional guidance offered virtually via
      phone or e-mail, and completed pretests and posttests of QI knowledge (maximum
      score = 15) and self-assessed confidence. A statistically significant difference
      in knowledge (pre-course mean = 7.75, standard deviation [SD] = 3.06; post-course
      mean = 11.75, SD = 3.28; P = .02) and self-assessed confidence (pre mean = 3.08,
      SD = 0.65; post mean = 4.5, SD = 0.68; P < .0001) was found. Of 8 faculty, 5 were
      able to conduct small tests of change; 3 studied the current processes and
      planned to run tests of change. Positive responses to this course helped obtain
      buy-in from leadership to develop a leadership program in QI. 

PMID- 25381004
TI  - Prevalence of genital prolapse symptoms in primary care: a cross-sectional
      survey.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of our study was to determine the prevalence
      of pelvic organ prolapse (POP) symptoms in a community-dwelling population in the
      United Kingdom. METHODS: All women over the age of 18 from a community practice
      were sent the validated International Consultation on Incontinence Questionnaire
      for vaginal symptoms (ICIQ-VS), to determine their POP symptoms. Data were
      analysed as numbers (raw data) and percentages of responders. Statistical
      comparisons were made using Chi-squared and Kruskal-Wallis tests as appropriate.
      RESULTS: Questionnaires were mailed to 3,412 women, 1,832 completed
      questionnaires were received (response 53.7 %). Symptoms strongly associated with
      prolapse; vaginal bulge/lump and bulge or lump outside of the vagina had a
      prevalence of 8.4 % and 4.9 % respectively. Vaginal symptoms, previous pelvic
      floor surgery, and age were statistically increased in those who had had a
      previous vaginal delivery. There were statistically worse scores (more symptoms)
      for the group with any vaginal delivery with regard to "feeling a loose or lax
      vagina", "a vaginal lump or bulge coming down in the vagina". There was a high
      prevalence of worry regarding sexual function, regardless of delivery status,
      with no statistically significant differences found between those who had had a
      vaginal delivery and those who had not. The group with no vaginal deliveries
      described a statistically significant increase in the reported sensation of "do
      you feel your vagina is too tight". CONCLUSIONS: Symptoms of POP were increased
      in those women who had experienced a vaginal delivery, whilst the sensation of
      having a tight vagina was decreased in those who had had a previous vaginal
      birth.

PMID- 25381006
TI  - A neuronal aging pattern unique to humans and common chimpanzees.
AB  - Lipofuscin pigment accumulation is among the most prominent markers of cellular
      aging in postmitotic cells. The formation of lipofuscin is related to oxidative
      enzymatic activity and free radical-induced lipid peroxidation. In various
      mammals such as rat, dog, macaque as well as in cheirogaleid primates, most of
      the large neurons, such as cerebellar Purkinje cells and neocortical pyramidal
      cells, show heavy lipofuscin accumulation in adulthood. In contrast, a well-known
      yet poorly studied feature of the aging human brain is that although lipofuscin
      accumulation is most marked in large neurons of the cerebral cortex, the large
      neurons of the cerebellar cortex-the Purkinje cells-appear to remain free of
      lipofuscin accumulation. It is however, not known whether this characteristic of
      human Purkinje cells is shared with other primates or other mammals. This study
      reports results from histological observation of Purkinje cells in humans, non
      human primates, and other mammals. Procedures include histochemistry,
      immunocytochemistry, and fluorescence microscopy. Abundant lipofuscin deposition
      was observed in Purkinje cells of all the species we examined except Homo sapiens
      (including Alzheimer's disease cases) and Pan troglodytes. In contrast,
      lipofuscin deposition was observed in neurons of the dentate nucleus. Our
      findings suggest that when compared with other primates, Purkinje cells in
      chimpanzees and humans might share a common aging pattern that involves
      mechanisms for neuroprotection. This observation is important when considering
      animal models of aging. 

PMID- 25381005
TI  - Phosphorylation of the AMPA receptor GluA1 subunit regulates memory load
      capacity.
AB  - Memory capacity (MC) refers to the number of elements one can maintain for a
      short retention interval. The molecular mechanisms underlying MC are unexplored.
      We have recently reported that mice as well as humans have a limited MC, which is
      reduced by hippocampal lesions. Here, we addressed the molecular mechanisms
      supporting MC. GluA1 AMPA-receptors (AMPA-R) mediate the majority of fast
      excitatory synaptic transmission in the brain and are critically involved in
      memory. Phosphorylation of GluA1 at serine residues S831 and S845 is promoted by
      CaMKII and PKA, respectively, and regulates AMPA-R function in memory duration.
      We hypothesized that AMPA-R phosphorylation may also be a key plastic process for
      supporting MC because it occurs in a few minutes, and potentiates AMPA-R ion
      channel function. Here, we show that knock-in mutant mice that specifically lack
      both of S845 and S831 phosphorylation sites on the GluA1 subunit had reduced MC
      in two different behavioral tasks specifically designed to assess MC in mice.
      This demonstrated a causal link between AMPA-R phosphorylation and MC. We then
      showed that information load regulates AMPA-R phosphorylation within the
      hippocampus, and that an overload condition associated with impaired memory is
      paralleled by a lack of AMPA-R phosphorylation. Accordingly, we showed that in
      conditions of high load, but not of low load, the pharmacological inhibition of
      the NMDA-CaMKII-PKA pathways within the hippocampus prevents memory as well as
      associated AMPA-R phosphorylation. These data provide the first identified
      molecular mechanism that regulates MC. 

PMID- 25381007
TI  - Crypto-rhombomeres of the mouse medulla oblongata, defined by molecular and
      morphological features.
AB  - The medulla oblongata is the caudal portion of the vertebrate hindbrain. It
      contains major ascending and descending fiber tracts as well as several motor and
      interneuron populations, including neural centers that regulate the visceral
      functions and the maintenance of bodily homeostasis. In the avian embryo, it has
      been proposed that the primordium of this region is subdivided into five segments
      or crypto-rhombomeres (r7-r11), which were defined according to either their
      parameric position relative to intersomitic boundaries (Cambronero and Puelles,
      in J Comp Neurol 427:522-545, 2000) or a stepped expression of Hox genes (Marin
      et al., in Dev Biol 323:230-247, 2008). In the present work, we examine the
      implied similar segmental organization of the mouse medulla oblongata. To this
      end, we analyze the expression pattern of Hox genes from groups 3 to 8, comparing
      them to the expression of given cytoarchitectonic and molecular markers, from mid
      gestational to perinatal stages. As a result of this approach, we conclude that
      the mouse medulla oblongata is segmentally organized, similarly as in avian
      embryos. Longitudinal structures such as the nucleus of the solitary tract, the
      dorsal vagal motor nucleus, the hypoglossal motor nucleus, the descending
      trigeminal and vestibular columns, or the reticular formation appear subdivided
      into discrete segmental units. Additionally, our analysis identified an internal
      molecular organization of the migrated pontine nuclei that reflects a
      differential segmental origin of their neurons as assessed by Hox gene
      expression. 

PMID- 25381008
TI  - A Rasch analysis of patients' opinions of primary health care professionals'
      ethical behaviour with respect to communication issues.
AB  - BACKGROUND: Patients' opinions are crucial in assessing the effectiveness of the
      ethical theories which underlie the care relationship between patients and
      primary health care professionals. OBJECTIVES: To study the ethical behaviour of
      primary health care professionals with respect to communication issues according
      to patients' opinions. METHODS: Cross-sectional study using a self-administered
      questionnaire in patients from a network of 15 urban primary health centres.
      Participants were patients attended at the centres when the study was conducted.
      We used a Rasch analysis to verify the structure of the 17 questionnaire items,
      and to calculate interval level measures for patients and items. We analysed
      differences according to patient subgroups using analysis of variance tests and
      differences between the endorsement of each item. RESULTS: We analysed 1013
      (70.34%) of questionnaires. Data fit to the Rasch model was achieved after
      collapsing two categories and eliminating five items. Items with the lowest
      degree of endorsement were related to the management of differences in
      conflictive situations between patients and health care professionals. We found
      significant differences (P < 0.001) in patients' opinions according to the degree
      of confidence in professionals and their educational level. CONCLUSIONS: Patients
      opined that empathy and traditional communication skills were respected by family
      physicians and nurses. However, opinions on endorsement were lower when patients
      disagreed with health care professionals. The differences found between patient
      subgroups demonstrated the importance of trust and confidence between patients
      and professionals.

PMID- 25381009
TI  - Belief in and use of complementary therapies among family physicians, internists
      and orthopaedists in Germany - cross-sectional survey.
AB  - BACKGROUND: Few studies have compared the belief in and the use of complementary
      and alternative medicine (CAM) across different medical specialties. OBJECTIVE:
      To investigate to what extent family physicians, internists and orthopaedists
      working in private practice in Germany (i) belief in the efficacy of CAM
      therapies; (ii) use these therapies for treating patients and (iii) whether
      beliefs and use are associated with basic professional attitudes. METHODS: A four
      page questionnaire was sent to nation-wide random samples of the three groups of
      physicians. Participants were asked to indicate their belief in the efficacy and
      their use of seven CAM treatments and to rate their agreement to statements on
      orthodox and heterodox professional views, patient-provider relationship and
      placebo effects. RESULTS: A total of 935 of 2018 (46%) physicians contacted sent
      back a questionnaire. The belief in specific effects of CAM therapies varied
      strongly within and between specialties, but overall many physicians hold
      positive views. Internists were more skeptic than family physicians and
      orthopaedists (P < 0.001); 23% of family physicians, 6% of internists and 31% of
      orthopaedists reported to use four or more CAM therapies more often than once a
      week. Frequent CAM use was strongly associated with being an orthopaedist and a
      higher overall belief in CAM modalities. Holding orthodox professional views
      predicted low CAM use. CONCLUSIONS: Many physicians (particularly, family
      physicians and orthopaedists) working in private practice in Germany use CAM
      therapies frequently and believe in their efficacy. Professional views and the
      specific working situation seem to influence use and believe strongly.

PMID- 25381010
TI  - Advance care planning in primary care, only for severely ill patients? A
      structured review.
AB  - BACKGROUND: Increasing medical possibilities, ageing of the population and the
      growing number of people with chronic illness appears to make advance care
      planning (ACP) inevitable. However, to what extent and how primary care providers
      (PCPs) provide ACP in daily practice is largely unknown. OBJECTIVE: To provide an
      overview of the actual practice of ACP in primary care. METHODS: We searched
      MEDLINE, EMBASE, CINAHL, PsycINFO and the Cochrane Library for empirical studies
      that described the practice of ACP with patients in primary health care. Studies
      focussing on non-adult patients, and hospital or nursing home settings were
      excluded. RESULTS: Ten articles met the inclusion criteria. The content of the
      ACP varied from discussing to refrain from cardiopulmonary resuscitation to
      existential issues. The prevalence ranged from 21% of PCPs having ACP discussions
      with the general elderly population to 69% having ACP discussions with terminal
      patients and 81% with patients with mild to moderate Alzheimer's disease. ACP was
      more common among cancer patients than among patients with non-cancer patients.
      Whether health care professionals or patients initiated ACP varied greatly.
      Advance directives and the Gold Standard Framework were perceived as helpful to
      guide ACP. CONCLUSIONS: ACP does not seem to have a systematic place in the care
      for all community-dwelling older people. Rather, it is used for specific groups,
      like patients with terminal disease, cancer and Alzheimer's Disease. Whether ACP
      might have beneficial effects for a broader primary care population, in terms of
      future care planning, is yet to be investigated.

PMID- 25381011
TI  - Advising patients on visual fitness to drive: implications of revised DVLA
      regulations.
AB  - AIM: To examine the relationship between the two UK vision standards for driving:
      the ability to read a number-plate at 20 m and achieving 6/12 (+0.30 logMAR).
      METHODS: 120 participants were assessed without refractive correction in this
      cross-sectional study. Vision was assessed with a Snellen chart, Early Treatment
      of Diabetic Retinopathy Study (ETDRS) style logMAR letter chart and logMAR chart
      using Landolt rings. Ability to read a post-2001 number-plate was assessed
      outdoors. RESULTS: For all charts, there was an 'overlap zone' of visions within
      which it was uncertain whether participants would pass the number-plate test.
      Within this zone, sensitivity and specificity of the 6/12 cut-off for predicting
      number-plate performance were reasonable for Snellen and ETDRS style charts, but
      poor for Landolt. All participants with 6/7.5 Snellen (+0.10 logMAR ETDRS) or
      better could read a number-plate. Some participants (2-6%) with vision between
      this level and 6/12 could not read a number-plate, and 14%-15% could read a
      number-plate but not achieve 6/12. CONCLUSIONS: To best predict drivers' ability
      to read a number-plate, vision should be assessed using a logMAR letter chart or
      a Snellen chart scored by full line. Drivers with 6/7.5 (+0.10 logMAR) or better
      vision can be advised that they meet the driving standard. Drivers with acuity
      between 6/9 and 6/12 (+0.12-+0.30 logMAR) should be advised to check their
      ability to read a number-plate, as some may not be able to. Clinicians will see
      patients who can read a number-plate, but do not achieve 6/12, who will need
      improved vision to meet visual requirements for driving.

PMID- 25381012
TI  - The impact of low-magnitude high-frequency vibration on fracture healing is
      profoundly influenced by the oestrogen status in mice.
AB  - Fracture healing is impaired in aged and osteoporotic individuals. Because
      adequate mechanical stimuli are able to increase bone formation, one
      therapeutical approach to treat poorly healing fractures could be the application
      of whole-body vibration, including low-magnitude high-frequency vibration
      (LMHFV). We investigated the effects of LMHFV on fracture healing in aged
      osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised
      (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice
      received a femur osteotomy that was stabilised using an external fixator. The
      mice received whole-body vibrations (20 minutes/day) with 0.3 G: peak-to-peak
      acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised
      femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated
      using bending-testing, micro-computed tomography (MUCT), histology and gene
      expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with
      significantly reduced flexural rigidity (-81%) and bone formation (-80%) in the
      callus. Gene expression analyses demonstrated increased oestrogen receptor beta
      (ERbeta, encoded by Esr2) and Sost expression in the callus of the vibrated
      animals, but decreased beta-catenin, suggesting that ERbeta might mediate these
      negative effects through inhibition of osteoanabolic Wnt/beta-catenin signalling.
      In contrast, in OVX mice, LMHFV significantly improved callus properties, with
      increased flexural rigidity (+1398%) and bone formation (+637%), which could be
      abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered
      in a 90-day-release pellet). On a molecular level, we found an upregulation of
      ERalpha in the callus of the vibrated OVX mice, whereas ERbeta was unaffected,
      indicating that ERalpha might mediate the osteoanabolic response. Our results
      indicate a major role for oestrogen in the mechanostimulation of fracture healing
      and imply that LMHFV might only be safe and effective in confined target
      populations. 

PMID- 25381015
TI  - Intralesional therapy for metastatic melanoma.
AB  - INTRODUCTION: Intralesional therapy for metastatic melanoma has some advantages
      over systemic therapy. Local drug administration allows for delivery of an
      increased concentration of the agent and reduced systemic exposure, thereby
      increasing local efficacy and limiting toxicity. Moreover, since in vivo tumor
      nodules contain the tumor antigens, this tumor tissue may serve as an autologous
      vaccine to induce systemic immunity. This so-called 'bystander effect', where
      uninjected distant lesions exhibit a response, has been reported in select
      intralesional therapy trials. AREAS COVERED: This review will give an overview of
      the working mechanisms, clinical evidence and side effects for available
      intralesional and topical therapies and summarize the most recent developments in
      this field. EXPERT OPINION: The ideal treatment approach for locoregionally
      advanced melanoma should be multidisciplinary and tailored to the patient, taking
      into consideration patient-related, tumor-related factors (such as location,
      tumor burden, mutation status) and previous treatments received. It will likely
      not be a single therapy, but rather a combination of injectable treatments,
      regional perfusions and systemic therapies.

PMID- 25381013
TI  - Tfap2a-dependent changes in mouse facial morphology result in clefting that can
      be ameliorated by a reduction in Fgf8 gene dosage.
AB  - Failure of facial prominence fusion causes cleft lip and palate (CL/P), a common
      human birth defect. Several potential mechanisms can be envisioned that would
      result in CL/P, including failure of prominence growth and/or alignment as well
      as a failure of fusion of the juxtaposed epithelial seams. Here, using geometric
      morphometrics, we analyzed facial outgrowth and shape change over time in a novel
      mouse model exhibiting fully penetrant bilateral CL/P. This robust model is based
      upon mutations in Tfap2a, the gene encoding transcription factor AP-2alpha, which
      has been implicated in both syndromic and non-syndromic human CL/P. Our findings
      indicate that aberrant morphology and subsequent misalignment of the facial
      prominences underlies the inability of the mutant prominences to fuse.
      Exencephaly also occured in some of the Tfap2a mutants and we observed additional
      morphometric differences that indicate an influence of neural tube closure
      defects on facial shape. Molecular analysis of the CL/P model indicates that Fgf
      signaling is misregulated in the face, and that reducing Fgf8 gene dosage can
      attenuate the clefting pathology by generating compensatory changes. Furthermore,
      mutations in either Tfap2a or Fgf8 increase variance in facial shape, but the
      combination of these mutations restores variance to normal levels. The
      alterations in variance provide a potential mechanistic link between clefting and
      the evolution and diversity of facial morphology. Overall, our findings suggest
      that CL/P can result from small gene-expression changes that alter the shape of
      the facial prominences and uncouple their coordinated morphogenesis, which is
      necessary for normal fusion. 

PMID- 25381014
TI  - Upregulation of CREM/ICER suppresses wound endothelial CRE-HIF-1alpha-VEGF
      dependent signaling and impairs angiogenesis in type 2 diabetes.
AB  - Impaired angiogenesis and endothelial dysfunction in type 2 diabetes constitute
      dominant risk factors for non-healing wounds and most forms of cardiovascular
      disease. We propose that diabetes shifts the 'angiogenic balance' in favor of an
      excessive anti-angiogenic phenotype. Herein, we report that diabetes impairs in
      vivo sponge angiogenic capacity by decreasing VEGF expression and fibrovascular
      invasion, and reciprocally enhances the formation of angiostatic molecules, such
      as thrombospondins, NFkappaB and FasL. Defective in vivo angiogenesis prompted
      cellular studies in cultured endothelial cells derived from subcutaneous sponge
      implants (SIECs) of control and Goto-Kakizaki rats. Ensuing data from diabetic
      SIECs demonstrated a marked upregulation in cAMP-PKA-CREB signaling, possibly
      stemming from increased expression of adenylyl cyclase isoforms 3 and 8, and
      decreased expression of PDE3. Mechanistically, we found that oxidative stress and
      PKA activation in diabetes enhanced CREM/ICER expression. This reduces IRS2
      cellular content by inhibiting cAMP response element (CRE) transcriptional
      activity. Consequently, a decrease in the activity of Akt-mTOR ensued with a
      concomitant reduction in the total and nuclear protein levels of HIF-1alpha.
      Limiting HIF-1alpha availability for the specific hypoxia response elements in
      diabetic SIECs elicited a marked reduction in VEGF expression, both at the mRNA
      and protein levels. These molecular abnormalities were illustrated functionally
      by a defect in various pro-angiogenic properties, including cell proliferation,
      migration and tube formation. A genetic-based strategy in diabetic SIECs using
      siRNAs against CREM/ICER significantly augmented the PKA-dependent VEGF
      expression. To this end, the current data identify the importance of CREM/ICER as
      a negative regulator of endothelial function and establish a link between
      CREM/ICER overexpression and impaired angiogenesis during the course of diabetes.
      Moreover, it could also point to CREM/ICER as a potential therapeutic target in
      the treatment of pathological angiogenesis. 

PMID- 25381016
TI  - Cardiopulmonary bypass considerations for pediatric patients on the ketogenic
      diet.
AB  - BACKGROUND: There is a population of children with epilepsy that is refractory to
      anti-epileptic drugs. The ketogenic diet, a high-fat, low-carbohydrate regimen,
      is one alternative treatment to decrease seizure activity. Special considerations
      are required for patients on the ketogenic diet undergoing cardiopulmonary bypass
      (CPB) to prevent exposure to glucose substrates that could alter ketosis,
      increasing the risk of recurrent seizures. CASE STUDY: A 2-year-old, 9 kilogram
      male with a history of infantile spasms with intractable epilepsy, trisomy 21
      status post tetralogy of Fallot repair, presented to the cardiac operating room
      for closure of a residual atrial septal defect. All disciplines of the surgical
      case minimized the use of carbohydrate-containing and contraindicated
      medications. Changes to the standard protocol and metabolic monitoring ensured
      the patient maintained ketosis. DISCUSSION: All disciplines within cardiac
      surgery need to be cognizant of patients on the ketogenic diet and prepare a
      modified protocol. Future monitoring considerations include thromboelastography,
      electroencephalography and continuous glucose measurement. Key areas of focus
      with this patient population in the cardiac surgical theater are to maintain a
      multidisciplinary approach, alter the required CPB prime components, address
      cardiac pharmacological concerns and limit any abnormal hematological
      occurrences.

PMID- 25381017
TI  - Overexpression of NRG1 promotes progression of gastric cancer by regulating the
      self-renewal of cancer stem cells.
AB  - BACKGROUND: Gastric cancer stem cells (GCSCs) have been successfully isolated
      from patients. However, the molecular mechanisms underlying the self-renewal of
      GCSCs and their relationship with the microenvironment are poorly characterized.
      METHODS: GCSCs and cancer-associated fibroblasts (CAFs) were cultured directly
      from gastric cancer patients. The self-renewal of GCSCs was assayed by sphere
      formation assay and in vivo tumorigenicity. Expression of neuregulin1 (NRG1) was
      examined by immunohistochemistry, real-time PCR and western blotting. RESULTS:
      CAFs increased the self-renewal of GCSCs by secreting NRG1. NRG1 activated NF
      kappaB signaling and this activation regulated GCSC self-renewal. Moreover, NF
      kappaB-active GCSCs were tumorigenic, however NF-kappaB-inactive GCSCs were not.
      The overexpression of NRG1 in stromal cells and cancer cells was observed in the
      tumor tissues of gastric cancer patients and was associated with clinical stage
      lymph node metastasis and survival in gastric cancer patients. In addition, we
      also found that NRG1 can regulate the proliferation and invasion of gastric
      cancer cells. CONCLUSIONS: These results indicate that NRG1, which can be
      secreted by CAFs or cancer cells, promotes progression of gastric cancer by
      regulating the self-renewal of GCSCs and its overexpression is associated with a
      prognosis of gastric cancer.

PMID- 25381019
TI  - Erratum to: Characteristics of single-case designs used to assess intervention
      effects in 2008.

PMID- 25381018
TI  - A new three-component formulation for the efficient whitening of teeth (Carbamide
      Plus).
AB  - OBJECTIVES: This study aimed to develop and characterise a new three-component
      dental whitening formulation which is as effective as the currently used
      carbamide peroxide but at significantly lower hydrogen peroxide concentrations.
      MATERIALS AND METHODS: The new formulation (Carbamide Plus) was prepared
      containing hydrogen peroxide, urea, and sodium tripolyphosphate and compared
      directly with carbamide peroxide (containing just hydrogen peroxide and urea). To
      evaluate the clinical effectiveness of 5% Carbamide Plus, a randomised double
      blind placebo-controlled clinical trial was conducted comparing the tooth colour
      of 33 patients using L*a*b* scores at baseline and after a 2-week whitening
      treatment. The behaviour of the three components in solution was determined by
      (1)H and (31)P NMR spectroscopy and pH dilution experiments. RESULTS: This
      clinical trial revealed that 5% whitening gels containing Carbamide Plus were as
      effective as those containing 10% carbamide peroxide. (1)H and (31)P NMR
      spectroscopy revealed strong intermolecular interactions between hydrogen
      peroxide and both urea and sodium tripolyphosphate (STPP) with little apparent
      interaction between urea and STPP. CONCLUSIONS: In this manuscript, we postulate
      that this increased whitening efficiency is due to a marked increase in local pH
      upon dilution which destabilises the hydrogen peroxide and expedites the
      whitening process. We postulate Carbamide Plus to be a three-component adduct
      with two molecules of carbamide peroxide binding to a central STPP unit with no
      direct interaction between STPP and urea. There were no statistically significant
      differences between Carbamide Plus and 10% carbamide peroxide in tooth-whitening
      achieved at 2 weeks. These results were recorded following 2 weeks of 2-h daily
      wear of at-home trays. CLINICAL RELEVANCE: Carbamide Plus offers the potential of
      using significantly lower levels of hydrogen peroxide concentration to achieve
      similar dental whitening effects.

PMID- 25381020
TI  - CancellationTools: All-in-one software for administration and analysis of
      cancellation tasks.
AB  - In a cancellation task, a participant is required to search for and cross out
      ("cancel") targets, which are usually embedded among distractor stimuli. The
      number of cancelled targets and their location can be used to diagnose the
      neglect syndrome after stroke. In addition, the organization of search provides a
      potentially useful way to measure executive control over multitarget search.
      Although many useful cancellation measures have been introduced, most fail to
      make their way into research studies and clinical practice due to the practical
      difficulty of acquiring such parameters from traditional pen-and-paper measures.
      Here we present new, open-source software that is freely available to all. It
      allows researchers and clinicians to flexibly administer computerized
      cancellation tasks using stimuli of their choice, and to directly analyze the
      data in a convenient manner. The automated analysis suite provides output that
      includes almost all of the currently existing measures, as well as several new
      ones introduced here. All tasks can be performed using either a computer mouse or
      a touchscreen as an input device, and an online version of the task runtime is
      available for tablet devices. A summary of the results is produced in a single A4
      sized PDF document, including high quality data visualizations. For research
      purposes, batch analysis of large datasets is possible. In sum, CancellationTools
      allows users to employ a flexible, computerized cancellation task, which provides
      extensive benefits and ease of use. 

PMID- 25381021
TI  - Response latencies are alive and well for identifying fakers on a self-report
      personality inventory: A reconsideration of van Hooft and Born (2012).
AB  - Van Hooft and Born (Journal of Applied Psychology 97:301-316, 2012) presented
      data challenging both the correctness of a congruence model of faking on
      personality test items and the relative merit (i.e., effect size) of response
      latencies for identifying fakers. We suggest that their analysis of response
      times was suboptimal, and that it followed neither from a congruence model of
      faking nor from published protocols on appropriately filtering the noise in
      personality test item answering times. Using new data and following recommended
      analytic procedures, we confirmed the relative utility of response times for
      identifying personality test fakers, and our obtained results, again, reinforce a
      congruence model of faking. 

PMID- 25381022
TI  - A Kinect-based system for automatic recording of some pigeon behaviors.
AB  - Contact switches and touch screens are the state of the art for recording
      pigeons' pecking behavior. Recording other behavior, however, requires a
      different sensor for each behavior, and some behaviors cannot easily be recorded.
      We present a flexible and inexpensive image-based approach to detecting and
      counting pigeon behaviors that is based on the Kinect sensor from Microsoft.
      Although the system is as easy to set up and use as the standard approaches, it
      is more flexible because it can record behaviors in addition to key pecking. In
      this article, we show how both the fast, fine motion of key pecking and the gross
      body activity of feeding can be measured. Five pigeons were trained to peck at a
      lighted contact switch, a pigeon key, to obtain food reward. The timing of the
      pecks and the food reward signals were recorded in a log file using standard
      equipment. The Kinect-based system, called BehaviorWatch, also measured the
      pecking and feeding behavior and generated a different log file. For key pecking,
      BehaviorWatch had an average sensitivity of 95% and a precision of 91%, which
      were very similar to the pecking measurements from the standard equipment. For
      detecting feeding activity, BehaviorWatch had a sensitivity of 95% and a
      precision of 97%. These results allow us to demonstrate that an advantage of the
      Kinect-based approach is that it can also be reliably used to measure activity
      other than key pecking.

PMID- 25381023
TI  - Adaptation of the International Affective Picture System (IAPS) for European
      Portuguese.
AB  - This study presents the results of the adaptation of the International Affective
      Picture System (IAPS) for European Portuguese (EP). Following the original
      procedure of Lang et al., 2000 native speakers of EP rated the 1,182 pictures of
      the last version of the IAPS set on the three affective dimensions of valence,
      arousal, and dominance, using the Self-Assessment Manikin (SAM). Results showed
      that the normative values of the IAPS for EP are properly distributed in the
      affective space of valence and arousal, showing the typical boomerang-shaped
      distribution observed in previous studies. Results also point to important
      differences in the way Portuguese females and males react to affective pictures
      that should be taken into consideration when planning and conducting research
      with Portuguese samples. Furthermore, the results from the cross-cultural
      comparisons between the EP ratings and the ratings from the American, Spanish,
      Brazilian, Belgian, Chilean, Indian, and Bosnian-Herzegovinian standardizations,
      showed that in spite of the fact that IAPS stimuli elicited affective responses
      that are similar across countries and cultures (at least in Western cultures),
      there are differences in the way Portuguese individuals react to IAPS pictures
      that strongly recommend the use of the normative values presented in this work.
      They can be downloaded as a supplemental archive at http://brm.psychonomic
      journals.org/content/supplemental or at http://p
      pal.di.uminho.pt/about/databases.

PMID- 25381024
TI  - Neonatal hyperoxia leads to persistent alterations in NK responses to influenza A
      virus infection.
AB  - Respiratory distress in preterm or low birth weight infants is often treated with
      supplemental oxygen. However, this therapy can disrupt normal lung development
      and architecture and alter responses to respiratory insults. Similarly, exposure
      of newborn mice to 100% oxygen during saccular lung development leads to
      permanent alveolar simplification, and upon challenge with influenza A virus,
      mice exhibit reduced host resistance. Natural killer (NK) cells are key players
      in antiviral immunity, and emerging evidence suggest they also help to maintain
      homeostasis in peripheral tissues, including the lung, by promoting epithelial
      cell regeneration via IL-22. We tested the hypothesis that adult mice exposed to
      hyperoxia as neonates have modified NK cell responses to infection. We report
      here that mice exposed to neonatal hyperoxia had fewer IL-22(+) NK cells in their
      lungs after influenza virus challenge and a parallel increase in IFN-gamma(+) NK
      cells. Using reciprocal bone marrow chimeric mice, we show that exposure of
      either hematopoietic or nonhematopoietic cells was sufficient to increase the
      severity of infection and to diminish the frequency of IL-22(+) NK cells in the
      infected lung. Overall, our findings suggest that neonatal hyperoxia leads to
      long-term changes in the reparative vs. cytotoxic nature of NK cells and that
      this is due in part to intrinsic changes in hematopoietic cells. These
      differences may contribute to how oxygen alters the host response to respiratory
      viral infections. 

PMID- 25381025
TI  - Muscarinic M3 receptors on structural cells regulate cigarette smoke-induced
      neutrophilic airway inflammation in mice.
AB  - Anticholinergics, blocking the muscarinic M3 receptor, are effective
      bronchodilators for patients with chronic obstructive pulmonary disease. Recent
      evidence from M(3) receptor-deficient mice (M(3)R(-/-)) indicates that M3
      receptors also regulate neutrophilic inflammation in response to cigarette smoke
      (CS). M(3) receptors are present on almost all cell types, and in this study we
      investigated the relative contribution of M(3) receptors on structural cells vs.
      inflammatory cells to CS-induced inflammation using bone marrow chimeric mice.
      Bone marrow chimeras (C56Bl/6 mice) were generated, and engraftment was confirmed
      after 10 wk. Thereafter, irradiated and nonirradiated control animals were
      exposed to CS or fresh air for four consecutive days. CS induced a significant
      increase in neutrophil numbers in nonirradiated and irradiated control animals (4
      to 35-fold). Interestingly, wild-type animals receiving M(3)R(-/-) bone marrow
      showed a similar increase in neutrophil number (15-fold). In contrast, no
      increase in the number of neutrophils was observed in M3R(-/-) animals receiving
      wild-type bone marrow. The increase in keratinocyte-derived chemokine (KC) levels
      was similar in all smoke-exposed groups (2.5- to 5.0-fold). Microarray analysis
      revealed that fibrinogen-alpha and CD177, both involved in neutrophil migration,
      were downregulated in CS-exposed M(3)R(-/-) animals receiving wild-type bone
      marrow compared with CS-exposed wild-type animals, which was confirmed by RT-qPCR
      (1.6-2.5 fold). These findings indicate that the M(3) receptor on structural
      cells plays a proinflammatory role in CS-induced neutrophilic inflammation,
      whereas the M(3) receptor on inflammatory cells does not. This effect is probably
      not mediated via KC release, but may involve altered adhesion and transmigration
      of neutrophils via fibrinogen-alpha and CD177.

PMID- 25381026
TI  - Novel regulators of endothelial barrier function.
AB  - Endothelial barrier function is an essential and tightly regulated process that
      ensures proper compartmentalization of the vascular and interstitial space, while
      allowing for the diffusive exchange of small molecules and the controlled
      trafficking of macromolecules and immune cells. Failure to control endothelial
      barrier integrity results in excessive leakage of fluid and proteins from the
      vasculature that can rapidly become fatal in scenarios such as sepsis or the
      acute respiratory distress syndrome. Here, we highlight recent advances in our
      understanding on the regulation of endothelial permeability, with a specific
      focus on the endothelial glycocalyx and endothelial scaffolds, regulatory
      intracellular signaling cascades, as well as triggers and mediators that either
      disrupt or enhance endothelial barrier integrity, and provide our perspective as
      to areas of seeming controversy and knowledge gaps, respectively. 

PMID- 25381030
TI  - Testing the Predictive Validity of the LSI-R Using a Sample of Young Male
      Offenders on Probation in Guangzhou, China.
AB  - This study explored the predictive validity of the Level of Service Inventory
      Revised (LSI-R) with 112 young male probationers on recidivism for new offense
      and rearrest in Guangzhou, China, from 2010 to 2013. Using bivariate
      correlations, logistic regression, and receiver operating characteristics (ROC)
      analysis, the LSI-R total score was found to be a stable and significant
      predictor of recidivism. The LSI-R total score and subscales of Criminal History
      and Leisure/Recreation were significantly correlated to recidivism. There was
      significant association between time at risk and recidivism. Increase in the LSI
      R total score was associated with greater likelihood that recidivism would occur.
      There was no recidivism in low-risk group, and higher recidivism rates were found
      in moderate-and high-risk groups. The LSI-R was effective in specifying
      recidivists and non-recidivists with area under the curve (AUC) coefficient of
      .733. The current study supports the utility of the LSI-R, which is applicable to
      different cultural and social contexts, as a risk/need assessment instrument for
      young male probationer recidivism in Guangzhou. Sufficient training and
      accumulated experience of administering the LSI-R would be necessary to reduce
      regional variation. Future studies with larger samples across different offender
      groups are needed. Limitations and implications for offender assessment in China
      are discussed. 

PMID- 25381029
TI  - Functional Interaction Between Na/K-ATPase and NMDA Receptor in Cerebellar
      Neurons.
AB  - NMDA receptors play a crucial role in regulating synaptic plasticity and memory.
      Activation of NMDA receptors changes intracellular concentrations of Na(+) and
      K(+), which are subsequently restored by Na/K-ATPase. We used immunochemical and
      biochemical methods to elucidate the potential mechanisms of interaction between
      these two proteins. We observed that NMDA receptor and Na/K-ATPase interact with
      each other and this interaction was shown for both isoforms of alpha subunit
      (alpha1 and alpha3) of Na/K-ATPase expressed in neurons. Using Western blotting,
      we showed that long-term exposure of the primary culture of cerebellar neurons to
      nanomolar concentrations of ouabain (a cardiotonic steroid, a specific ligand of
      Na/K-ATPase) leads to a decrease in the levels of NMDA receptors which is likely
      mediated by the alpha3 subunit of Na/K-ATPase. We also observed a decrease in
      enzymatic activity of the alpha1 subunit of Na/K-ATPase caused by NMDA receptor
      activation. This effect is mediated by an increase in intracellular Ca(2+). Thus,
      Na/K-ATPase and NMDA receptor can interact functionally by forming a
      macromolecular complex which can be important for restoring ionic balance after
      neuronal excitation. Furthermore, this interaction suggests that NMDA receptor
      function can be regulated by endogenous cardiotonic steroids which recently have
      been found in cerebrospinal fluid or by pharmacological drugs affecting Na/K
      ATPase function. 

PMID- 25381027
TI  - CFTR and lung homeostasis.
AB  - CFTR is a cAMP-activated chloride and bicarbonate channel that is critical for
      lung homeostasis. Decreases in CFTR expression have dire consequences in cystic
      fibrosis (CF) and have been suggested to be a component of the lung pathology in
      chronic obstructive pulmonary disease. Decreases or loss of channel function
      often lead to mucus stasis, chronic bacterial infections, and the accompanying
      chronic inflammatory responses that promote progressive lung destruction, and,
      eventually in CF, lung failure. Here we discuss CFTR's functional role airway
      surface liquid hydration and pH, in regulation of other channels such as the
      epithelial sodium channel, and in regulating inflammatory responses in the lung. 

PMID- 25381028
TI  - A critical review of the American Journal of Physiology-Lung Cellular and
      Molecular Physiology: 2012-2015.
AB  - I have had the privilege of serving as Editor-in-Chief of the American Journal of
      Physiology: Lung Cellular and Molecular Physiology from 1/1/2012 to 1/1/2015 and
      have been reappointed for another 3-year term. When I took over as editor, I
      published an editorial in AJP-Lung in which I highlighted my vision and outlined
      the tasks to be accomplished to transform AJP-Lung into "The best place to
      publish basic, translational, and hypothesis-driven clinical lung research."
      Herein I review our accomplishments during the first term. As promised, we review
      each article submitted to this journal and our reviews always help the quality
      and impact of every paper. We recognized the contributions of junior authors by
      establishing a number of awards and increased the visibility of AJP-Lung by
      establishing Facebook and Blog electronic pages and sponsoring symposia in
      scientific meetings. Our impact factor increased from 3.523 in 2011 to 4.041 in
      2012 and, thanks to our calls for papers, we are receiving large numbers of high
      quality papers in all aspects of pulmonary cell biology and lung diseases. The
      best is yet to come. 

PMID- 25381031
TI  - Transculturalism and risk factors for violent behavior.

PMID- 25381033
TI  - Advanced glycation end products induce oxidative stress and mitochondrial
      dysfunction in SH-SY5Y cells.
AB  - This study aimed to investigate the direct effects of advanced glycation end
      products (AGEs) on the mitochondrial structure and function of SH-SY5Y cells and
      the possible molecular mechanism(s) underlying mitochondria dysfunction by AGEs.
      SH-SY5Y cells were cultured in 400 MUg/ml of AGE-bovine serum albumin (BSA) for
      24 h, and changes in the mitochondrial function of SH-SY5Y cells were analysed as
      follows. Reactive oxygen species (ROS) were detected using 2',7'
      dichlorodihydrofluorescein diacetate molecular probes. Mitochondrial membrane
      potential (DeltaPsim) was determined by flow cytometry using fluorescent probes.
      The expression of cytochrome c (Cyt c) protein level was assessed by Western
      blotting. Mitochondrial structures were observed by transmission electron
      microscopy. Our results showed that AGE-BSA induced an increase in ROS levels, a
      decrease in mitochondrial DeltaPsim, and the release of Cyt c from mitochondria
      in SH-SY5Y cells. The mitochondria of SH-SY5Y cells showed remarkable swelling
      and vacuolisation, but these changes were recovered after pretreatment with
      neutralising anti-receptor for advanced glycation end products (RAGE) antibody.
      Our results suggested that AGE-BSA induced mitochondrial dysfunction in SH-SY5Y
      cells through RAGE pathways. Thus, AGEs are potential mechanistic links between
      diabetes mellitus and Alzheimer's disease. 

PMID- 25381032
TI  - A randomized control trial to assess the impact of vitamin D supplementation
      compared to placebo on vascular stiffness in chronic kidney disease patients.
AB  - BACKGROUND: Vitamin D deficiency is associated with cardiovascular (CV) risk in
      multiple populations, including those with chronic kidney disease (CKD). The
      active form of the hormone (1,25 OH2D3) binds to receptors in multiple organs.
      CKD patients are deficient in both 25 Vitamin D and 1,25 OH2D3. Clinical trial
      data demonstrating the benefits of vitamin D formulations are limited, and fail
      to show significant benefits on CV outcomes, and have compared different
      compounds, in various populations, and focused on a variety of outcomes. A
      understanding of the mechanism by which different vitamin D compounds confer CV
      protection in CKD is important for the design of future studies. METHODS/DESIGN:
      This 3 arm randomized prospective double-blinded placebo-controlled study
      examining the impact of calcitriol (1,25 OH2D3) and 25-hydroxyvitamin D3
      supplementation compared to placebo on vascular stiffness, as measured by pulse
      wave velocity (PWV). Patients are enrolled from 2 tertiary care institutions if
      they meet inclusion criteria (stable estimated glomerular filtration rate (eGFR)
      between 15-45ml/min, <+/-5ml/min change in previous 6 months), on stable doses of
      renin-angiotensin aldosterone system blockade. For those already receiving
      vitamin D therapies, a 3 month washout period before randomization is mandatory.
      Treatment duration is 6 months; medications are given thrice weekly in fixed
      doses. The primary outcome measure is Vascular stiffness, measured non-invasively
      by pulse wave velocity (PWV). Other measurements include BP, kidney function and
      serial blood levels of biomarkers. The primary analysis will compare any vitamin
      D therapy versus placebo for the primary outcome defined as the change of PWV
      from baseline to 6 months. Analysis of covariance will be used to detect
      differences between vitamin D preparations in the magnitude of reduction in PWV.
      DISCUSSION: This study is novel in that we are using a robust study design in CKD
      patients (not on dialysis) comparing placebo to different forms of vitamin D
      supplementation in fixed doses, irrespective of baseline values. We hope to
      demonstrate the biological mechanistic effect of vitamin D supplementation on
      vascular function in order for this information to be used in designing larger
      randomized controlled trials. TRIAL REGISTRATION: Current Controlled Trials
      NCT01247311. Date of Registration: November 12, 2010.

PMID- 25381034
TI  - Rhynchophorus ferrugineus midgut cell line to evaluate insecticidal potency of
      different plant essential oils.
AB  - Cell cultures can be a potent and strong tool to evaluate the insecticidal
      efficiency of natural products. Plant essential oils have long been used as the
      fragrance or curative products around the world which means that they are safer
      to be used in close proximity of humans and mammals. In this study, a midgut cell
      line, developed from Rhynchophorus ferrugineus (RPW-1), was used for screening
      essential oils from nine different plants. Assays revealed that higher cell
      mortality was observed at 500 ppm which reached to 86, 65, 60, 59, 56, 54, 54,
      53, and 53%, whereas lowest cell mortality at 1 ppm remained at 41, 23, 20, 17,
      16, 15, 14, 13, and 10%, for Azadirachta indica, Piper nigrum, Mentha spicata,
      Cammiphora myrrha, Elettaria cardamomum, Zingiber officinale, Curcuma longa,
      Schinus molle, and Rosmarinus officinalis, respectively. 3-(4,5-Dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay revealed the
      percentage of cell growth inhibition was highest at 500 ppm and remained at 48,
      45, 42, 37, 34, 29, 24, 22, and 18% against A. indica, P. nigrum, M. spicata, C.
      myrrha, E. cardamomum, Z. officinale, C. longa, S. molle, and R. officinalis,
      respectively. Lowest LC50 value (7.98 ppm) was found for A. indica, whereas the
      highest LC50 (483.11 ppm) was against R. officinalis. Thus, in this study,
      essential oils of A. indica exhibited the highest levels of toxicity, whereas
      those from R. officinalis exhibited the lowest levels of toxicity toward RPW-1
      cells.

PMID- 25381035
TI  - Characterization and miRNA-mediated posttranscriptional regulation of vitelline
      membrane outer layer protein I in the adult chicken oviduct.
AB  - The laying hen is the best model for oviduct growth and development. The chicken
      oviduct produces the egg components, including the egg white and eggshell.
      However, the mechanism of egg component production during oviduct development
      requires further investigation. Vitelline membrane outer layer protein 1 (VMO-1)
      is found in the outer layer of the vitelline membrane of avian eggs. Comparison
      of the chicken VMO-1 protein-coding sequence and the human, mouse, rat, and
      bovine VMO-1 proteins via multiple sequence alignment analysis revealed high
      degrees of homology of 55%, 53%, 48%, and 54%, respectively. Although the avian
      homologue of VMO-1 is highly expressed in the magnum of the oviduct, little is
      known about the transcriptional and posttranscriptional regulation of VMO-1
      during oviduct development. The results of this study revealed that estrogen
      induces VMO-1 messenger RNA (mRNA) expression in oviduct cells in vitro. The
      expression of genes interacting with VMO-1 by RNA interference (RNAi) functional
      analysis revealed that ovomucin expression was decreased by VMO-1 silencing. In
      addition, gga-miR-1623, 1552-3p, and 1651-3p influenced VMO-1 expression via its
      3'-UTR, suggesting the posttranscriptional regulation of VMO-1 expression in
      chickens. Collectively, these results suggest that VMO-1 is an estrogen-induced
      gene that is posttranscriptionally regulated by microRNAs (miRNAs). The present
      study may contribute to an understanding of egg component production during
      chicken oviduct development.

PMID- 25381037
TI  - Establishment and characterization of a new cell line of Chilo suppressalis
      Walker (Lepidoptera: Pyralididae).
AB  - A new cell line, designated as ZJBIQ-Chsu-I, was initiated from the fat body of
      larval Chilo suppressalis (Walker) (Lepidoptera: Pyralididae) in TNM-FH insect
      medium containing 15% fetal bovine serum. The polygonal cells (65.6%) were
      predominant among various cell types, and the diameter range was from 12.63 to
      22.50 MUm. The cell line showed a typical lepidopteran chromosome pattern ranging
      from 108 to 136 chromosomes in the majority of the cells. The population doubling
      time (PDT) of the cell line at the 15th passage was 62 h. This cell line was
      found to be susceptible to Spodoptera exigua nuclear polyhedrosis virus (SeNPV).
      By the DNA amplification fingerprinting polymerase chain reaction (DAF-PCR)
      technique, it was confirmed that cell line ZJBIQ-Chsu-I really originated from C.
      suppressalis.

PMID- 25381036
TI  - Fisetin induces apoptosis in human nonsmall lung cancer cells via a mitochondria
      mediated pathway.
AB  - The present study investigated the apoptotic effects of fisetin, a phenolic
      compound, against the human nonsmall cell lung cancer cell line, NCI-H460.
      Fisetin showed dose-dependent cytotoxic activity against NCI-H460 cells, with 50%
      inhibition of cell viability occurring at a concentration of 75 MUg/mL. Fisetin
      induced both the production of intracellular reactive oxygen species and
      apoptosis, as evidenced by apoptotic body formation, DNA fragmentation, an
      increase in the number of sub-G1 phase cells, and mitochondrial membrane
      depolarization. Moreover, fisetin significantly modulated the expression of
      apoptosis-associated proteins, resulting in reduced expression of B cell lymphoma
      2, increased expression of Bcl-2-associated X protein, and activation of caspase
      9 and caspase-3. In addition, pretreatment with a caspase inhibitor blocked
      fisetin-induced cell death.

PMID- 25381038
TI  - Health burden and costs of obesity and overweight in Germany: an update.
AB  - In 2011, Konnopka et al. (Eur J Health Econ 12:345-352, 2011) published a top
      down cost of illness study on the health burden, and direct and indirect costs of
      morbidity and mortality attributable to excess weight (BMI >=25 kg/m(2)) in
      Germany in 2002. The objective of the current study was to update the 2002
      estimates to the year 2008. To simplify comparisons, we closely followed the
      methods and assumptions of the original study, using 2008 data for most input
      parameters (e.g. prevalence, mortality, resource use, costs). Excess weight
      related deaths increased by 31% (from 36,653 to 47,964) and associated years of
      potential life lost (from 428,093 to 588,237) and quality adjusted life years
      lost (from 367,722 to 505,748) by about 37%, respectively. Excess weight caused
      ?16,797 million in total costs in 2008 (+70%), of which ?8,647 million were
      direct costs (corresponding to 3.27% of total German health care expenditures in
      2008). About 73% (?12,235 million) of total excess weight related costs were
      attributable to obesity (BMI >=30 kg/m(2)). The main drivers of direct costs were
      endocrinological (44%) and cardiovascular (38%) diseases. Indirect costs amounted
      to ?8,150 million in 2008 (+62%), of which about two-thirds were indirect costs
      from unpaid work. The great majority of indirect costs were due to premature
      mortality (?5,669 million). The variation of input parameters (univariate
      sensitivity analyses) resulted in attributable costs between ?8,978 million (-47%
      compared to base case) and ?25,060 million (+49%). The marked increase in excess
      weight related costs can largely be explained by increases in the prevalence of
      overweight and obesity, and to a lesser extent from increases in resource
      consumption, as well as increases in (unit) costs and wages (comprising 5.5%
      inflation).

PMID- 25381039
TI  - Some economics on personalized and predictive medicine.
AB  - OBJECTIVE: To contribute to the theoretical literature on personalized medicine,
      analyzing and integrating in an economic model, the decision a health authority
      faces when it must decide on the implementation of personalized medicine in a
      context of uncertainty. METHODS: We carry out a stylized model to analyze the
      decision health authorities face when they do not have perfect information about
      the best treatment for a population of patients with a given disease. The health
      authorities decide whether to use a test to match patients with treatments
      (personalized medicine) to maximize health outcomes. Our model characterizes the
      situations under which personalized medicine dominates the alternative option of
      business-as-usual (treatment without previous test). We apply the model to the
      KRAS test for colorectal cancer, the PCA3 test for prostate cancer and the PCR
      test for the X-fragile syndrome, to illustrate how the parameters and variables
      of the model interact. RESULTS: Implementation of personalized medicine requires,
      as a necessary condition, having some tests with high discriminatory power. This
      is not a sufficient condition and expected health outcomes must be taken into
      account to make a decision. When the specificity and the sensitivity of the test
      are low, the health authority prefers to apply a treatment to all patients
      without using the test. When both characteristic of the test are high, the health
      authorities prefer to personalize the treatments when expected health outcomes
      are better than those under the standard treatment. When we applied the model to
      the three aforementioned tests, the results illustrate how decisions are adopted
      in real world. CONCLUSIONS: Although promising, the use of personalized medicine
      is still under scrutiny as there are important issues demanding a response.
      Personalized medicine may have an impact in the drug development processes, and
      contribute to the efficiency and effectiveness of health care delivery.
      Nevertheless, more accurate statistical and economic information related to tests
      results and treatment costs as well as additional medical information on the
      efficacy of the treatments are needed to adopt decisions that incorporate
      economic rationality.

PMID- 25381040
TI  - EGFR and IGF-1R in regulation of prostate cancer cell phenotype and polarity:
      opposing functions and modulation by T-cadherin.
AB  - T-cadherin is an atypical glycosylphosphatidylinsoitol-anchored member of the
      cadherin superfamily of adhesion molecules. We found that T-cadherin
      overexpression in malignant (DU145) and benign (BPH-1) prostatic epithelial cell
      lines or silencing in the BPH-1 cell line, respectively, promoted or inhibited
      migration and spheroid invasion in collagen I gel and Matrigel. T-cadherin
      dependent effects were associated with changes in cell phenotype: overexpression
      caused cell dissemination and loss of polarity evaluated by relative positioning
      of the Golgi/nuclei in cell groups, whereas silencing caused formation of compact
      polarized epithelial-like clusters. Epidermal growth factor receptor (EGFR) and
      IGF factor-1 receptor (IGF-1R) were identified as mediators of T-cadherin
      effects. These receptors per se had opposing influences on cell phenotype. EGFR
      activation with EGF or IGF-1R inhibition with NVP-AEW541 promoted dissemination,
      invasion, and polarity loss. Conversely, inhibition of EGFR with gefitinib or
      activation of IGF-1R with IGF-1 rescued epithelial morphology and decreased
      invasion. T-cadherin silencing enhanced both EGFR and IGF-1R phosphorylation, yet
      converted cells to the morphology typical for activated IGF-1R. T-cadherin
      effects were sensitive to modulation of EGFR or IGF-1R activity, suggesting
      direct involvement of both receptors. We conclude that T-cadherin regulates
      prostate cancer cell behavior by tuning the balance in EGFR/IGF-1R activity and
      enhancing the impact of IGF-1R.

PMID- 25381042
TI  - Endocrinology and art. King Ariarathes IV of Cappadocia: coins reveal enlarged
      thyroid (188 BC).

PMID- 25381041
TI  - Nonconsensual withdrawal of nutrition and hydration in prolonged disorders of
      consciousness: authoritarianism and trustworthiness in medicine.
AB  - The Royal College of Physicians of London published the 2013 national clinical
      guidelines on prolonged disorders of consciousness (PDOC) in vegetative and
      minimally conscious states. The guidelines acknowledge the rapidly advancing
      neuroscientific research and evolving therapeutic modalities in PDOC. However,
      the guidelines state that end-of-life decisions should be made for patients who
      do not improve with neurorehabilitation within a finite period, and they
      recommend withdrawal of clinically assisted nutrition and hydration (CANH). This
      withdrawal is deemed necessary because patients in PDOC can survive for years
      with continuation of CANH, even when a ceiling on medical care has been imposed,
      i.e., withholding new treatment such as cardiopulmonary resuscitation for acute
      life-threatening illness. The end-of-life care pathway is centered on a staged
      escalation of medications, including sedatives, opioids, barbiturates, and
      general anesthesia, concurrent with withdrawal of CANH. Agitation and distress
      may last from several days to weeks because of the slow dying process from
      starvation and dehydration. The potential problems of this end-of-life care
      pathway are similar to those of the Liverpool Care Pathway. After an independent
      review in 2013, the Department of Health discontinued the Liverpool Care pathway
      in England. The guidelines assert that clinicians, supported by court decisions,
      have become the final authority in nonconsensual withdrawal of CANH on the basis
      of "best interests" rationale. We posit that these guidelines lack high-quality
      evidence supporting: 1) treatment futility of CANH, 2) reliability of distress
      assessment from starvation and dehydration, 3) efficacy of pharmacologic control
      of this distress, and 4) proximate causation of death. Finally, we express
      concerns about the utilitarian-based assessment of what constitutes a person's
      best interests. We are disturbed by the level and the role of medical
      authoritarianism institutionalized by these national guidelines when deciding on
      the worthiness of life in PDOC. We conclude that these guidelines are not only
      harmful to patients and families, but they represent the means of nonconsensual
      euthanasia. The latter would constitute a gross violation of the public's trust
      in the integrity of the medical profession. 

PMID- 25381043
TI  - A child with tumour thrombus extending to the right atrium.

PMID- 25381044
TI  - The feasibility of ureteral tissue engineering using autologous veins: an
      orthotopic animal model with long term results.
AB  - BACKGROUND: In an earlier study we demonstrated the feasibility to create tissue
      engineered venous scaffolds in vitro and in vivo. In this study we investigated
      the use of tissue engineered constructs for ureteral replacement in a long term
      orthotopic minipig model. In many different projects well functional ureretal
      tissue was established using tissue engineering in animals with short-time follow
      up (12 weeks). Therefore urothelial cells were harvested from the bladder,
      cultured, expanded in vitro, labelled with fluorescence and seeded onto the
      autologous veins, which were harvested from animals during a second surgery.
      Three days after cell seeding the right ureter was replaced with the cell-seeded
      matrices in six animals, while further 6 animals received an unseeded vein for
      ureteral replacement. The animals were sacrificed 12, 24, and 48 weeks after
      implantation. Gross examination, intravenous pyelogram (IVP), H&E staining,
      Trichrome Masson's Staining, and immunohistochemistry with pancytokeratin
      AE1/AE3, smooth muscle alpha actin, and von Willebrand factor were performed in
      retrieved specimens. RESULTS: The IVP and gross examination demonstrated that no
      animals with tissue engineered ureters and all animals of the control group
      presented with hydronephrosis after 12 weeks. In the 24-week group, one tissue
      engineered and one unseeded vein revealed hydronephrosis. After 48 weeks all
      tissue engineered animals and none of the control group showed hydronephrosis on
      the treated side. Histochemistry and immunohistochemistry revealed a multilayer
      of urothelial cells attached to the seeded venous grafts. CONCLUSIONS: Venous
      grafts may be a potential source for ureteral reconstruction. The results of so
      far published ureteral tissue engineering projects reveal data up to 12 weeks
      after implantation. Even if the animal numbers of this study are small, there is
      an increasing rate of hydronephrosis revealing failure of ureteral tissue
      engineering with autologous matrices in time points longer than 3 months after
      implantation. Further investigations have to prove adequate clinical outcome and
      appropriate functional long-term results.

PMID- 25381045
TI  - Melanin: a photoprotection for Bacillus thuringiensis based biopesticides.
AB  - Melanins are negatively-charged, hydrophobic, dark high molecular weight
      irregular biopolymers, composed of polymerized phenolic and/or indolic compounds.
      They are produced by most organisms. Bacillus thuringiensis is a Gram-positive,
      spore-forming, soil bacterium and the most successful biological control agent
      that produces distinctly shaped crystals during sporulation that have
      insecticidal activity. However, one of the main disadvantages is that the
      insecticidal activity of B. thuringiensis formulation is unstable and rapidly
      loses its activity under field conditions due to UV radiation. Melanin absorbs
      radiation; therefore photoprotection of B. thuringiensis based on melanin has
      been studied and is herewith reviewed. 

PMID- 25381046
TI  - Health economic aspects of vertebral augmentation procedures.
AB  - We reviewed all peer-reviewed papers analysing the cost-effectiveness of
      vertebroplasty and balloon kyphoplasty for osteoporotic vertebral compression
      fractures. In general, the procedures appear to be cost effective but are very
      dependent upon model input details. Better data, rather than new models, are
      needed to answer outstanding questions. Vertebral augmentation procedures (VAPs),
      including vertebroplasty (VP) and balloon kyphoplasty (BKP), seek to stabilise
      fractured vertebral bodies and reduce pain. The aim of this paper is to review
      current literature on the cost-effectiveness of VAPs as well as to discuss the
      challenges for economic evaluation in this research area. A systematic literature
      search was conducted to identify existing published studies on the cost
      effectiveness of VAPs in patients with osteoporosis. Only peer-reviewed published
      articles that fulfilled the criteria of being regarded as full economic
      evaluations including both morbidity and mortality in the outcome measure in the
      form of quality-adjusted life years (QALYs) were included. The search identified
      949 studies, of which four (0.4 %) were identified as relevant with one study
      added later. The reviewed studies differed widely in terms of study design,
      modelling framework and data used, yielding different results and conclusions
      regarding the cost-effectiveness of VAPs. Three out of five studies indicated in
      the base case results that VAPs were cost effective compared to non-surgical
      management (NSM). The five main factors that drove the variations in the cost
      effectiveness between the studies were time horizon, quality of life effect of
      treatment, offset time of the treatment effect, reduced number of bed days
      associated with VAPs and mortality benefit with treatment. The cost-effectiveness
      of VAPs is uncertain. In answering the remaining questions, new cost
      effectiveness analysis will yield limited benefit. Rather, studies that can
      reduce the uncertainty in the underlying data, especially regarding the long-term
      clinical outcomes of VAPs, should be conducted.

PMID- 25381047
TI  - Effects of zoledronic acid versus placebo on bone mineral density and bone
      texture analysis assessed by the trabecular bone score in premenopausal women
      with breast cancer treatment-induced bone loss: results of the ProBONE II
      substudy.
AB  - Changes in bone mineral density (BMD) and trabecular bone score (TBS) were
      assessed in 70 patients who received either zoledronate (ZOL) (n = 34) or placebo
      (n = 36) for 2 years. In premenopausal women with breast cancer treatment-induced
      bone loss, 24 months of intravenous ZOL treatment significantly increased the
      lumbar spine BMD and the TBS. INTRODUCTION: The aim of this study was to compare
      the effects of 4 mg intravenous zoledronate (ZOL) versus placebo (PLB), every 3
      months, on the lumbar spine (LS) bone mineral density (BMD) and the trabecular
      bone score (TBS) in premenopausal women with breast cancer (BC) treatment-induced
      bone loss. The TBS is a gray-level texture measurement which is related to the
      bone microarchitecture and considered to be independent of the BMD. METHODS:
      Changes in BMD and TBS were assessed in 70 patients who were recruited in the
      double-blind, placebo-controlled ProBONE-II trial and randomized to receive
      either ZOL (n = 34) or PLB (n = 36) for 2 years. The changes were assessed at
      baseline and at 12 and 24 months after treatment initiation. RESULTS: Patients
      receiving ZOL showed a mean increase in LS BMD from the baseline to 12 (2.17%)
      and 24 months (3.14%) of treatment and a mean increase in the TBS of 2.41 and
      0.75%, respectively. Conversely, patients receiving PLB showed a mean decrease in
      the LS BMD from the baseline to 12 (-5.02%) and 24 (-6.43%) months and a mean
      decrease of -0.52 and -2.16% in the TBS, respectively. Changes in the BMD and the
      TBS from the baseline to 12 and 24 months were all significantly different for
      ZOL compared to PLB (p < 0.005). Furthermore, BMD and TBS showed a moderate
      correlation ranging from 0.28 (p = 0.087) to 0.47 (p = 0.003). CONCLUSIONS: In
      premenopausal women with BC, 24 months of intravenous ZOL treatment significantly
      increased the LS BMD as well as the TBS.

PMID- 25381048
TI  - Improving operating room turnover time: a systems based approach.
AB  - Operating room (OR) turnover time (TT) has a broad and significant impact on
      hospital administrators, providers, staff and patients. Our objective was to
      identify current problems in TT management and implement a consistent,
      reproducible process to reduce average TT and process variability. Initial
      observations of TT were made to document the existing process at a 511 bed, 24
      OR, academic medical center. Three control groups, including one consisting of
      Orthopedic and Vascular Surgery, were used to limit potential confounders such as
      case acuity/duration and equipment needs. A redesigned process based on observed
      issues, focusing on a horizontally structured, systems-based approach has three
      major interventions: developing consistent criteria for OR readiness, utilizing
      parallel processing for patient and room readiness, and enhancing perioperative
      communication. Process redesign was implemented in Orthopedics and Vascular
      Surgery. Comparisons of mean and standard deviation of TT were made using an
      independent 2-tailed t-test. Using all surgical specialties as controls (n =
      237), mean TT (hh:mm:ss) was reduced by 0:20:48 min (95 % CI, 0:10:46-0:30:50),
      from 0:44:23 to 0:23:25, a 46.9 % reduction. Standard deviation of TT was reduced
      by 0:10:32 min, from 0:16:24 to 0:05:52 and frequency of TT>=30 min was reduced
      from 72.5to 11.7 %. P < 0.001 for each. Using Vascular and Orthopedic surgical
      specialties as controls (n = 13), mean TT was reduced by 0:15:16 min (95 % CI,
      0:07:18-0:23:14), from 0:38:51 to 0:23:35, a 39.4 % reduction. Standard deviation
      of TT reduced by 0:08:47, from 0:14:39 to 0:05:52 and frequency of TT>=30 min
      reduced from 69.2 to 11.7 %. P < 0.001 for each. Reductions in mean TT present
      major efficiency, quality improvement, and cost-reduction opportunities. An OR
      redesign process focusing on parallel processing and enhanced communication
      resulted in greater than 35 % reduction in TT. A systems-based focus should drive
      OR TT design.

PMID- 25381049
TI  - Optimization of noise in non-integrated instrumentation amplifier for the
      amplification of very low electrophysiological [corrected] signals. Case of
      electro cardio graphic signals (ECG).
AB  - In this paper we present an instrumentation amplifier with discrete elements and
      optimized noise for the amplification of very low signals. In amplifying signals
      of very weak amplitude, the noise can completely absorb these signals if the used
      amplifier does not present the optimal guarantee to minimize the noise. Based on
      related research and re-viewing of recent patents Journal of Medical Systems,
      30:205-209, 2006, we suggest an approach of noise reduction in amplification much
      more thoroughly than re-viewing of recent patents and we deduce from it the
      general criteria necessary and essential to achieve this optimization. The
      comparison of these criteria with the provisions adopted in practice leads to the
      inadequacy of conventional amplifiers for effective noise reduction. The
      amplifier we propose is an instrumentation amplifier with active negative
      feedback and optimized noise for the amplification of signals with very low
      amplitude. The application of this method in the case of electro cardio graphic
      signals (ECG) provides simulation results fully in line with forecasts.

PMID- 25381050
TI  - Genetic fuzzy system for mortality risk assessment in cardiac surgery.

PMID- 25381051
TI  - Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase
      inhibitor, in patients with B cell malignancies.
AB  - PURPOSE: Ibrutinib is an oral Bruton's tyrosine kinase inhibitor, recently
      approved for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic
      leukemia (CLL) patients with at least one prior therapy. We developed a
      population pharmacokinetic (PK) model for ibrutinib in patients. METHODS:
      Ibrutinib PK data (3,477 observations/245 patients) were available from the
      following clinical studies: (1) A phase I dose-escalation study in recurrent B
      cell malignancies (dose levels of 1.25-12.5 mg/kg/day and fixed dose of 560
      mg/day); (2) a phase II study in MCL (fixed dose level of 560 mg/day); (3) a
      phase Ib/II dose-finding study in CLL (fixed dose levels of 420 and 840 mg/day).
      Different compartmental PK models were explored using nonlinear mixed effects
      modeling. RESULTS: A two-compartment PK model with sequential zero-first-order
      absorption and first-order elimination was able to characterize the PK of
      ibrutinib. The compound was rapidly absorbed, had a high oral plasma clearance
      (approximately 1,000 L/h) and a high apparent volume of distribution at steady
      state (approximately 10,000 L). PK parameters were not dependent on dose, study,
      or clinical indication. The fasting state was characterized by a 67 % relative
      bioavailability compared with the meal conditions used in the trials and
      administration after a high-fat meal. Body weight and coadministration of
      antacids marginally increased volume of distribution and duration of absorption,
      respectively. CONCLUSIONS: The proposed population PK model was able to describe
      the plasma concentration-time profiles of ibrutinib across various trials. The
      linear model indicated that the compound's PK was dose independent and time
      independent.

PMID- 25381053
TI  - Metagenomic analysis of the shrew enteric virome reveals novel viruses related to
      human stool-associated viruses.
AB  - Shrews are small insectivorous mammals that are distributed worldwide. Similar to
      rodents, shrews live on the ground and are commonly found near human residences.
      In this study, we investigated the enteric virome of wild shrews in the genus
      Crocidura using a sequence-independent viral metagenomics approach. A large
      portion of the shrew enteric virome was composed of insect viruses, whilst novel
      viruses including cyclovirus, picornavirus and picorna-like virus were also
      identified. Several cycloviruses, including variants of human cycloviruses
      detected in cerebrospinal fluid and stools, were detected in wild shrews at a
      high prevalence rate. The identified picornavirus was distantly related to human
      parechovirus, inferring the presence of a new genus in this family. The
      identified picorna-like viruses were characterized as different species of
      calhevirus 1, which was discovered previously in human stools. Complete or nearly
      complete genome sequences of these novel viruses were determined in this study
      and then were subjected to further genetic characterization. Our study provides
      an initial view of the diversity and distinctiveness of the shrew enteric virome
      and highlights unique novel viruses related to human stool-associated viruses. 

PMID- 25381055
TI  - Transformed cell-specific induction of apoptosis by porcine circovirus type 1
      viral protein 3.
AB  - Several members of the family Circoviridae have been shown to encode proteins
      with apoptotic activity. For example, both porcine circovirus type 2 (PCV2) and
      chicken anemia virus (CAV) encode a third viral protein (VP3) that has been shown
      to be cytotoxic. Interestingly, in the case of the CAV protein (designated
      apoptin), apoptosis is specific to transformed cell types. Similarities in genome
      structure and organization suggest that PCV type 1 (PCV1) may also contain a
      third ORF, which codes for a protein with homologous activity. To investigate
      this, ORF prediction followed by gene expression analyses were conducted on a
      gene found to be homologous to CAV and PCV2 VP3. Our data presented herein
      elucidate a putative ORF3 that codes for a viral protein with functional
      similarity to that of apoptin and PCV2 VP3. Unlike its homologues, sequence
      analysis revealed a highly hydrophobic, extended C-terminal domain in PCV1 VP3,
      which harbours a strong nuclear export signal. Subcellular localization analysis
      demonstrated divergent PCV1 VP3 localization patterns compared with that of CAV
      VP3. Interestingly, cytotoxicity studies revealed evidence that apoptosis may be
      selective to transformed cell types, similar to apoptin; however, PCV1 VP3
      induced a dramatic G1 cell cycle arrest as opposed to the G2/M arrest observed
      with apoptin. These results indicate that nuclear localization of PCV1 VP3 is
      necessary neither for induction of apoptosis nor for transformed cell
      selectivity, and suggest a mechanism of action distinct from that of apoptin. 

PMID- 25381054
TI  - Cell culture adaptation mutations in foot-and-mouth disease virus serotype A
      capsid proteins: implications for receptor interactions.
AB  - In this study we describe the adaptive changes fixed on the capsid of several
      foot-and-mouth disease virus serotype A strains during propagation in cell
      monolayers. Viruses passaged extensively in three cell lines (BHK-21, LFBK and IB
      RS-2) consistently gained positively charged amino acids in the putative heparin
      sulfate-binding pocket (VP2 betaE-betaF loop, VP1 C-terminus and VP3 beta-B knob)
      surrounding the fivefold symmetry axis (VP1 betaF-betaG loop) and at other
      discrete sites on the capsid (VP3 betaG-betaH loop, VP1 C-terminus, VP2 betaC
      strand and VP1 betaG-betaH loop). A lysine insertion in the VP1 betaF-betaG loop
      of two of the BHK-21-adapted viruses supports the biological advantage of
      positively charged residues acquired in cell culture. The charge transitions
      occurred irrespective of cell line, suggesting their possible role in ionic
      interaction with ubiquitous negatively charged cell-surface molecules such as
      glycosaminoglycans (GAG). This was supported by the ability of the cell-culture
      adapted variants to replicate in the integrin-deficient, GAG-positive CHO-K1
      cells and their superior fitness in competition assays compared with the lower
      passage viruses with WT genotypes. Substitutions fixed in the VP1 betaG-betaH
      loop (-3, -2 and +2 'RGD' positions) or in the structural element known to be
      juxtaposed against that loop (VP1 betaB-betaC loop) suggest their possible role
      in modulating the efficiency and specificity of interaction of the 'RGD' motif
      with alphav-integrin receptors. The nature and location of the substitutions
      described in this study could be applied in the rapid cell culture adaptation of
      viral strains for vaccine production. 

PMID- 25381056
TI  - Elicitation of T-cell responses by structural and non-structural proteins of
      coxsackievirus B4.
AB  - Coxsackievirus B4 (CV-B4) belongs to the genus Enterovirus within the family
      Picornaviridae. To investigate target proteins recognized by T-cells in human
      enterovirus B infections, virus-encoded structural [VP0 (VP4 and VP2), VP1, VP3]
      and non-structural (2A, 2B, 2C, 3C and 3D) proteins were expressed and purified
      in Escherichia coli. Peripheral blood of 19 healthy adult donors was used to
      create enterovirus-specific T-cell lines by repeated stimulation with CV-B4 cell
      lysate antigen. T-cell lines responded in individual patterns, and responses to
      all purified proteins were observed. The most often recognized enteroviral
      protein was VP0, which is the fusion between the most conserved structural
      proteins, VP4 and VP2. T-cell responses to VP0 were detected in 15 of the 19 (79
      %) donor lines. Non-structural 2C protein was recognized in 11 of the 19 (58 %)
      lines, and 11 of the 19 (58 %) lines also had a response to 3D protein.
      Furthermore, responses to other non-structural proteins (2A, 2B and 3C) were also
      detected. T-cell responses did not correlate clearly to the individual HLA-DR-DQ
      phenotype or the history of past coxsackie B virus infections of the donors. 

PMID- 25381057
TI  - RNA transcripts of full-length cDNA clones of rabbit hepatitis E virus are
      infectious in rabbits.
AB  - Hepatitis E virus (HEV), the causative agent of hepatitis E, is a single-stranded
      positive-sense RNA virus belonging to the family Hepeviridae. At least four
      genotypes of the family infect humans: genotypes 1 and 2 are transmitted to
      humans through contaminated water, while genotypes 3 and 4 are zoonotic and have
      animal reservoirs. A novel strain of HEV recently identified in rabbits is a
      distant member of genotype 3, and thus poses a potential risk of zoonotic
      transmission to humans. The objective of this study was to construct and
      characterize an infectious cDNA clone of the rabbit HEV. Two full-length cDNA
      clones of rabbit HEV, pT7g-rabHEV and pT7-rabHEV, were constructed and their
      infectivity was tested by in vitro transfection of Huh7 human liver cells and by
      direct intrahepatic inoculation of rabbits with capped RNA transcripts. Results
      showed that positive signal for rabbit HEV protein was detected by an
      immunofluorescence assay with a HEV-specific antibody in Huh7 human liver cells
      transfected with capped RNA transcripts from the two full-length cDNA clones.
      Rabbits intrahepatically inoculated with capped RNA transcripts from each of the
      two clones developed active HEV infection as evidenced by seroconversion to anti
      HEV antibodies, and detection of rabbit HEV RNA in sera and feces of inoculated
      animals. The availability of a rabbit HEV infectious cDNA clone now affords us
      the ability to delineate the mechanism of HEV replication and cross-species
      infection in a small animal model. 

PMID- 25381058
TI  - Role of the lipid rafts in the life cycle of canine coronavirus.
AB  - Coronaviruses are enveloped RNA viruses that have evolved complex relationships
      with their host cells, and modulate their lipid composition, lipid synthesis and
      signalling. Lipid rafts, enriched in sphingolipids, cholesterol and associated
      proteins, are special plasma membrane microdomains involved in several processes
      in viral infections. The extraction of cholesterol leads to disorganization of
      lipid microdomains and to dissociation of proteins bound to lipid rafts. Because
      cholesterol-rich microdomains appear to be a general feature of the entry
      mechanism of non-eneveloped viruses and of several coronaviruses, the purpose of
      this study was to analyse the contribution of lipids to the infectivity of canine
      coronavirus (CCoV). The CCoV life cycle is closely connected to plasma membrane
      cholesterol, from cell entry to viral particle production. The methyl-beta
      cyclodextrin (MbetaCD) was employed to remove cholesterol and to disrupt the
      lipid rafts. Cholesterol depletion from the cell membrane resulted in a dose
      dependent reduction, but not abolishment, of virus infectivity, and at a
      concentration of 15 mM, the reduction in the infection rate was about 68 %.
      MbetaCD treatment was used to verify if cholesterol in the envelope was required
      for CCoV infection. This resulted in a dose-dependent inhibitory effect, and at a
      concentration of 9 mM MbetaCD, infectivity was reduced by about 73 %. Since viral
      entry would constitute a target for antiviral strategies, inhibitory molecules
      interacting with viral and/or cell membranes, or interfering with lipid
      metabolism, may have strong antiviral potential. It will be interesting in the
      future to analyse the membrane microdomains in the CCoV envelope. 

PMID- 25381059
TI  - Acetylome profiling reveals overlap in the regulation of diverse processes by
      sirtuins, gcn5, and esa1.
AB  - Although histone acetylation and deacetylation machineries (HATs and HDACs)
      regulate important aspects of cell function by targeting histone tails, recent
      work highlights that non-histone protein acetylation is also pervasive in
      eukaryotes. Here, we use quantitative mass-spectrometry to define acetylations
      targeted by the sirtuin family, previously implicated in the regulation of non
      histone protein acetylation. To identify HATs that promote acetylation of these
      sites, we also performed this analysis in gcn5 (SAGA) and esa1 (NuA4) mutants. We
      observed strong sequence specificity for the sirtuins and for each of these HATs.
      Although the Gcn5 and Esa1 consensus sequences are entirely distinct, the sirtuin
      consensus overlaps almost entirely with that of Gcn5, suggesting a strong
      coordination between these two regulatory enzymes. Furthermore, by examining
      global acetylation in an ada2 mutant, which dissociates Gcn5 from the SAGA
      complex, we found that a subset of Gcn5 targets did not depend on an intact SAGA
      complex for targeting. Our work provides a framework for understanding how HAT
      and HDAC enzymes collaborate to regulate critical cellular processes related to
      growth and division. 

PMID- 25381060
TI  - C-terminomics screen for natural substrates of cytosolic carboxypeptidase 1
      reveals processing of acidic protein C termini.
AB  - Cytosolic carboxypeptidases (CCPs) constitute a new subfamily of M14
      metallocarboxypeptidases associated to axonal regeneration and neuronal
      degeneration, among others. CCPs are deglutamylating enzymes, able to catalyze
      the shortening of polyglutamate side-chains and the gene-encoded C termini of
      tubulin, telokin, and myosin light chain kinase. The functions of these enzymes
      are not entirely understood, in part because of the lack of information about C
      terminal protein processing in the cell and its functional implications. By means
      of C-terminal COFRADIC, a positional proteomics approach, we searched for
      cellular substrates targets of CCP1, the most relevant member of this family. We
      here identified seven new putative CCP1 protein substrates, including ribosomal
      proteins, translation factors, and high mobility group proteins. Furthermore, we
      showed for the first time that CCP1 processes both glutamates as well as C
      terminal aspartates. The implication of these C termini in molecular interactions
      furthermore suggests that CCP1-mediated shortening of acidic protein tails might
      regulate protein-protein and protein-DNA interactions. 

PMID- 25381061
TI  - HGAL localization to cell membrane regulates B-cell receptor signaling.
AB  - Human germinal center-associated lymphoma (HGAL) is specifically expressed only
      in germinal center (GC) B lymphocytes and GC-derived lymphomas. HGAL protein
      decreases lymphocyte motility by inhibiting the ability of myosin to translocate
      actin via direct interaction with F-actin and myosin II and by activating RhoA
      signaling via direct interactions with RhoA-specific guanine nucleotide exchange
      factors. HGAL protein also regulates B-cell receptor (BCR) signaling by directly
      binding to and enhancing Syk kinase activity and activation of its downstream
      effectors. Herein we demonstrate that HGAL protein can be myristoylated and
      palmitoylated and that these modifications localize HGAL to cellular membrane
      raft microdomains with distinct consequences for BCR signaling and
      chemoattractant-induced cell mobility. In BCR signaling, raft localization of
      HGAL facilitates interaction with Syk and modulation of the BCR activation and
      signaling, which induces HGAL phosphorylation and redistribution from lipid raft
      to bulk membrane and cytoplasm, followed by degradation. In contrast, HGAL
      myristoylation and palmitoylation avert its inhibitory effects on chemoattractant
      induced cell motility. These findings further elucidate the growing and complex
      role of HGAL in B-cell biology and suggest that membrane-bound and cytoplasmic
      HGAL protein differently regulates distinct biological processes. 

PMID- 25381062
TI  - Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a
      predominant involvement of RAS/RTK signaling pathways.
AB  - Myeloid malignancies bearing chromosomal inv(3)/t(3;3) abnormalities are among
      the most therapy-resistant leukemias. Deregulated expression of EVI1 is the
      molecular hallmark of this disease; however, the genome-wide spectrum of
      cooperating mutations in this disease subset has not been systematically
      elucidated. Here, we show that 98% of inv(3)/t(3;3) myeloid malignancies harbor
      mutations in genes activating RAS/receptor tyrosine kinase (RTK) signaling
      pathways. In addition, hemizygous mutations in GATA2, as well as heterozygous
      alterations in RUNX1, SF3B1, and genes encoding epigenetic modifiers, frequently
      co-occur with the inv(3)/t(3;3) aberration. Notably, neither mutational patterns
      nor gene expression profiles differ across inv(3)/t(3;3) acute myeloid leukemia,
      chronic myeloid leukemia, and myelodysplastic syndrome cases, suggesting
      recognition of inv(3)/t(3;3) myeloid malignancies as a single disease entity
      irrespective of blast count. The high incidence of activating RAS/RTK signaling
      mutations may provide a target for a rational treatment strategy in this high
      risk patient group.

PMID- 25381064
TI  - T-cell-associated cellular immunotherapy for lung cancer.
AB  - PURPOSE: The aim of the present study was to discuss recent findings on the role
      of T cells in lung cancer to provide information on their potential application,
      especially in cellular immunotherapy. METHODS: Data on the different types of T
      cells that are currently used for the treatment of lung cancer were obtained by
      searching the PUBMED database. RESULTS: Cytotoxic T lymphocytes, natural killer T
      cells, gammadelta T cells, lymphokine-activated killer cells, tumor-infiltrating
      lymphocytes, cytokine-induced killer cells and gene-modified T cells were
      analyzed to determine the benefits and drawbacks of their application in the
      treatment of lung cancer. Advances in the study of their antitumor mechanisms and
      directions for future research were discussed. CONCLUSIONS: T cells are critical
      for tumorigenesis and therefore important targets for the treatment of lung
      cancer. T-cell-associated cellular immunotherapy opens up a window of opportunity
      for the development of complementary methods to traditional lung cancer
      treatments, which warrants further investigation to improve the clinical outcomes
      of lung cancer patients.

PMID- 25381065
TI  - Novel COL9A3 mutation in a family diagnosed with multiple epiphyseal dysplasia: a
      case report.
AB  - BACKGROUND: Multiple epiphyseal dysplasia is a common skeletal dysplasia
      characterized by mild short stature, early-onset osteoarthritis mainly involving
      the hip and knee joints, and abnormally small and/or irregular epiphyses.
      Multiple epiphyseal dysplasia is clinically and genetically heterogeneous and six
      genes are associated with the phenotype of multiple epiphyseal dysplasia. CASE
      PRESENTATION: A 12-year-old Korean boy presented with intermittent knee pain. His
      height was 144.6 cm (20th percentile) and family history was notable for early
      onset osteoarthritis in his father. The proband's x-rays revealed epiphyseal
      changes characteristic of multiple epiphyseal dysplasia associated with a
      collagen IX defect, with manifestations primarily restricted to the knees.
      Mutational analysis identified a novel c.104G>A substitution in exon 2 of COL9A3,
      resulting in p.Gly35Asp in the proband and his father. In silico analyses
      predicted the p.Gly35Asp amino acid change to be detelerious, and molecular
      dynamics simulation demonstrated a major structural change in the heterotrimeric
      collagen IX. CONCLUSION: So far, three COL9A3 mutations, have been reported.
      These three mutations are located at the splice donor or acceptor site of COL9A3
      and cause skipping of exon 3, resulting in the deletion of 12 aminoacids in the
      COL3 domain of COL9A3. In contrast, the novel missense mutation identified in
      this two-generation family with multiple epiphyseal dysplasia is a missense
      mutation affecting the Gly residue of the Pro-Pro-Gly repeat sequence in the COL3
      domain of collage IX, with accompanying major structural change of the collagen
      peptide.

PMID- 25381066
TI  - Practice-based research networks at the crossroads of research translation.
AB  - Practice-based research networks (PBRNs) are "experimental farms" for research
      that matters in clinical practice. One of the defining characteristics of PBRNs
      is their ability to operate across a wide range of the bidirectional "pipeline of
      research translation," from clinical trials to informing health care policy.
      Developing effective translational approaches requires significant
      experimentation with new or innovatively combined research methods and
      theoretical frameworks. While the first decades of PBRN research generated a
      substantial body of evidence for improving individual practices (horizontal
      movement), PBRNs now find themselves at the multidimensional crossroads of
      patient-centeredness and community/population health (vertical movement). This
      practice-based research theme issue of the Journal of the American Board of
      Family Medicine provides a rich, cross-sectional synopsis of PBRN activities
      encompassing T2 translation, core practice-based research, implementation and
      dissemination research, community practice, and contributions to health care
      policy.

PMID- 25381063
TI  - Cytokine-induced killer (CIK) cells in cancer immunotherapy: report of the
      international registry on CIK cells (IRCC).
AB  - PURPOSE: Cytokine-induced killer (CIK) cells represent an exceptional T cell
      population uniting a T cell and natural killer cell like phenotype in their
      terminally differentiated CD3(+)CD56(+) subset, which features non-MHC-restricted
      tumor-killing activity. CIK cells are expandable from peripheral blood
      mononuclear cells and mature following the addition of certain cytokines. CIK
      cells have provided encouraging results in initial clinical studies and revealed
      synergistic antitumor effects when combined with standard therapeutic procedures.
      METHODS: Therefore, we established the international registry on CIK cells in
      order to collect and evaluate data about clinical trials using CIK cells for the
      treatment of cancer patients. Moreover, our registry is expected to set new
      standards on the reporting of results from clinical trials using CIK cells.
      Clinical responses, overall survival (OS), adverse reactions and immunologic
      effects were analyzed in 45 studies present in our database. These studies
      investigated 22 different tumor entities altogether enrolling 2,729 patients.
      RESULTS: A mean response rate of 39 % and significantly increased OS, accompanied
      by an improved quality of life, were reported. Interestingly, side effects of CIK
      cell treatment were minor. Mild fevers, chills, headache and fatigue were,
      however, seen regularly after CIK cell infusion. Moreover, CIK cells revealed
      numerous immunologic effects such as changes in T cell subsets, tumor markers,
      cytokine secretion and HBV viral load. CONCLUSION: Due to their easy availability
      and potent antitumor activity, CIK cells emerged as a promising immunotherapy
      approach in oncology and may gain major importance on the prognosis of cancer.

PMID- 25381068
TI  - Who will establish a proper data model for family medicine and primary care?

PMID- 25381067
TI  - Praxis-based research networks: An emerging paradigm for research that is
      rigorous, relevant, and inclusive.
AB  - Practice-based research networks (PBRNs) have developed a grounded approach to
      conducting practice-relevant and translational research in community practice
      settings. Seismic shifts in the health care landscape are shaping PBRNs that work
      across organizational and institutional margins to address complex problems.
      Praxis-based research networks combine PBRN knowledge generation with
      multistakeholder learning, experimentation, and application of practical
      knowledge. The catalytic processes in praxis-based research networks are cycles
      of action and reflection based on experience, observation, conceptualization, and
      experimentation by network members and partners. To facilitate co-learning and
      solution-building, these networks have a flexible architecture that allows
      pragmatic inclusion of stakeholders based on the demands of the problem and the
      needs of the network. Praxis-based research networks represent an evolving trend
      that combines the core values of PBRNs with new opportunities for relevance,
      rigor, and broad participation.

PMID- 25381069
TI  - Practice-based innovations: More relevant and transportable than NIH-funded
      studies.
AB  - In 2003, the National Institutes of Health (NIH) created a translational science
      funding stream to foster widespread, practice-based dissemination of scientific
      evidence. A decade later, our study of a national cohort of innovative practices
      suggests that effective dissemination continues to be prevented by the limited
      biomedical focus of funded research, conventional research strategies, and
      failure to report contextual factors.

PMID- 25381070
TI  - A systematic process for recruiting physician-patient dyads in practice-based
      research networks (PBRNs).
AB  - BACKGROUND: Recruiting physicians and patients for primary care research is
      difficult, and low participation can greatly affect the validity of research.
      While practice-based research networks (PBRNs) offer advantages of scale for
      recruitment, the barriers are perennial. We designed a systematic process for
      recruiting physician-patient dyads in PBRNs and tested it in EXACKTE2, a large,
      cross-sectional, dyadic study. METHODS: Based on known barriers, we designed a
      systematic process for recruiting dyads of family physicians and their patients
      and implemented it in 2 primary care practice-based research networks in Canada:
      one in Ontario (11 practices) and one in Quebec (6 practices). Dyads (one
      physician with one patient) were recruited simultaneously to explore their mutual
      influence during consultations. A key element of the process was a research
      assistant assigned to each practice. This person closely accompanied the
      recruitment process, liaising with staff and taking charge of interviews,
      questionnaires, and follow-up. RESULTS: In total, 276 physicians and patients
      were recruited in 17 primary care practices in 2 primary care networks in Ontario
      and Quebec, representing a participation rate of more than 72% of eligible
      physicians and more than 64% of eligible patients. CONCLUSION: We established a
      systematic process to conduct successful dyadic recruitment of physicians and
      patients in PBRNs.

PMID- 25381071
TI  - Guidance for researchers developing and conducting clinical trials in practice
      based research networks (PBRNs).
AB  - BACKGROUND: There is increased interest nationally in multicenter clinical trials
      to answer questions about clinical effectiveness, comparative effectiveness, and
      safety in real-world community settings. Primary care practice-based research
      networks (PBRNs), comprising community- and/or academically affiliated practices
      committed to improving medical care for a range of health problems, offer ideal
      settings for these trials, especially pragmatic clinical trials. However, many
      researchers are not familiar with working with PBRNs. METHODS: Experts in
      practice-based research identified solutions to challenges that researchers and
      PBRN personnel experience when collaborating on clinical trials in PBRNs. These
      were organized as frequently asked questions in a draft document presented at a
      2013 Agency for Health care Research and Quality PBRN conference workshop,
      revised based on participant feedback, then shared with additional experts from
      the DARTNet Institute, Clinical Translational Science Award PBRN, and North
      American Primary Care Research Group PBRN workgroups for further input and
      modification. RESULTS: The "Toolkit for Developing and Conducting Multi-site
      Clinical Trials in Practice-Based Research Networks" offers guidance in the areas
      of recruiting and engaging practices, budgeting, project management, and
      communication, as well as templates and examples of tools important in developing
      and conducting clinical trials. CONCLUSION: Ensuring the successful development
      and conduct of clinical trials in PBRNs requires a highly collaborative approach
      between academic research and PBRN teams.

PMID- 25381072
TI  - Practice-based research networks (PBRNs) are promising laboratories for
      conducting dissemination and implementation research.
AB  - Dissemination and implementation science addresses the application of research
      findings in varied health care settings. Despite the potential benefit of
      dissemination and implementation work to primary care, ideal laboratories for
      this science have been elusive. Practice-based research networks (PBRNs) have a
      long history of conducting research in community clinical settings, demonstrating
      an approach that could be used to execute multiple research projects over time in
      broad and varied settings. PBRNs also are uniquely structured and increasingly
      involved in pragmatic trials, a research design central to dissemination and
      implementation science. We argue that PBRNs and dissemination and implementation
      scientists are ideally suited to work together and that the collaboration of
      these 2 groups will yield great value for the future of primary care and the
      delivery of evidence-based health care.

PMID- 25381073
TI  - Use of community engagement strategies to increase research participation in
      practice-based research networks (PBRNs).
AB  - PURPOSE: Practice-based research networks (PBRNs) are increasingly encouraged to
      use community engagement approaches. The extent to which PBRNs engage clinic and
      community partners in strategies to recruit and retain participants from their
      local communities (specifically racial/ethnic communities) is the focus of this
      study. METHODS: The design was a cross-sectional survey of PBRN directors in the
      United States. Survey respondents indicated whether their research network
      planned for, implemented, and has capacity for activities that engage clinic and
      community partners in 7 recommended strategies organized into study phases,
      called the cycle of trust. The objectives of the national survey were to (1)
      describe the extent to which PBRNs across the United States routinely implement
      the strategies recommended for recruiting diverse patient groups and (2) identify
      factors associated with implementing the recommended strategies. RESULTS: The
      survey response rate was 63%. Activities that build trust often are used more
      with clinic partners than with community partners. PBRNs that adopt engagement
      strategies when working with clinic and community partners have less difficulty
      in recruiting diverse populations. Multivariate analysis showed that the
      targeting racial/ethnic communities for study recruitment, Clinical and
      Translational Science Award affiliation, and planning to use community engagement
      strategies were independent correlates of PBRN implementation of the recommended
      strategies. CONCLUSION: PBRNs that successfully engage racial/ethnic communities
      as research partners use community engagement strategies. New commitments are
      needed to support PBRN researchers in developing relationships with the
      communities in which their patients live. Stable PBRN infrastructure funding that
      appreciates the value of maintaining community engagement between funded studies
      is critical to the research enterprise that values translating research findings
      into generalizable care models for patients in the community.

PMID- 25381074
TI  - Achieving meaningful use of electronic health records (EHRs) in primary care:
      Proposed critical processes from the Kentucky Ambulatory Network (KAN).
AB  - OBJECTIVE: The Kentucky Ambulatory Network, a practice-based research network,
      conducted this study to propose critical processes for electronic health record
      (EHR) implementation. METHODS: Periodic observation of the implementation process
      and assessment of meaningful use (MU) metrics within 10 small primary care
      practices working with a regional extension center. RESULTS: Through focus groups
      and structured interviews, the strategies, processes, and procedures used by
      these practices to achieve MU of EHRs were determined. Implementation themes
      related to and critical processes associated with EHR adoption were proposed.
      CONCLUSIONS: Five proposed critical processes for EHR adoption and achievement of
      MU were identified; these processes were supported by 70% (7 of 10) of the study
      practices meeting MU criteria.

PMID- 25381075
TI  - Use of mobile health (mHealth) tools by primary care patients in the WWAMI region
      Practice and Research Network (WPRN).
AB  - PURPOSE: The purpose of this study was to determine the prevalence of mobile
      health (mHealth) use among primary care patients and examine demographic and
      clinical correlates. METHODS: Adult patients who presented to 1 of 6 primary care
      clinics in a practice-based research network in the northwest United States
      during a 2-week period received a survey that assessed smartphone ownership;
      mHealth use; sociodemographic characteristics (age, sex, race/ethnicity, health
      literacy); chronic conditions; and depressive symptoms (2-item Patient Health
      Questionnaire). Data analysis used descriptive statistics and mixed logistic
      regression. RESULTS: Of 918 respondents (estimated response rate, 67.4%), 55%
      owned a smartphone, among whom 70% were mHealth users. In multivariate analyses,
      smartphone ownership and mHealth use were not associated with health literacy,
      chronic conditions, or depression but were less common among adults >45 years old
      (adjusted odds ratio, 0.07-0.39; P < .001). Only 10% of patients learned about
      mHealth tools from their physician, and few (31%) prioritized their provider's
      involvement. CONCLUSIONS: Use of mHealth technologies is lower among older adults
      but otherwise is common among primary care patients, including those with limited
      health literacy and those with chronic conditions. Findings support the potential
      role of mHealth in improving disease management among certain groups in need;
      however, greater involvement of health care providers may be important for
      realizing this potential.

PMID- 25381077
TI  - Laboratory medicine handoff gaps experienced by primary care practices: A report
      from the shared networks of collaborative ambulatory practices and partners
      (SNOCAP).
AB  - BACKGROUND: The majority of errors in laboratory medicine testing are thought to
      occur in the pre- and postanalytic testing phases, and a large proportion of
      these errors are secondary to failed handoffs. Because most laboratory tests
      originate in ambulatory primary care, understanding the gaps in handoff processes
      within and between laboratories and practices is imperative for patient safety.
      Therefore, the purpose of this study was to understand, based on information from
      primary care practice personnel, the perceived gaps in laboratory processes as a
      precursor to initiating process improvement activities. DESIGN: A survey was used
      to assess perceptions of clinicians, staff, and management personnel of gaps in
      handoffs between primary care practices and laboratories working in 21 Colorado
      primary care practices. Data were analyzed to determine statistically significant
      associations between categorical variables. In addition, qualitative analysis of
      responses to open-ended survey questions was conducted. RESULTS: Primary care
      practices consistently reported challenges and a desire/need to improve their
      efforts to systematically track laboratory test status, confirm receipt of
      laboratory results, and report results to patients. Automated tracking systems
      existed in roughly 61% of practices, and all but one of those had electronic
      health record-based tracking systems in place. One fourth of these electronic
      health record-enabled practices expressed sufficient mistrust in these systems to
      warrant the concurrent operation of an article-based tracking system as backup.
      Practices also reported 12 different procedures used to notify patients of test
      results, varying by test result type. CONCLUSION: The results highlight the lack
      of standardization and definition of roles in handoffs in primary care laboratory
      practices for test ordering, monitoring, and receiving and reporting test
      results. Results also identify high-priority gaps in processes and the
      perceptions by practice personnel that practice improvement in these areas is
      needed. Commonalities in these areas warrant the development and support of tools
      for use in primary care settings.

PMID- 25381076
TI  - Results of nurse navigator follow-up after positive colorectal cancer screening
      test: a randomized trial.
AB  - BACKGROUND: Follow-up after a positive colorectal cancer screening test is
      necessary for screening to be effective. We hypothesized that nurse navigation
      would increase the completion of colonoscopy after a positive screening test.
      METHODS: This study was conducted between 2008 and 2012 at 21 primary care
      medical centers in western Washington State. Participants in the Systems of
      Support to Increase Colorectal Cancer Screening study who had a positive fecal
      occult blood test (FOBT) or flexible sigmoidoscopy needing follow-up were
      randomized to usual care (UC) or a nurse navigator (navigation). UC included an
      electronic health record-based positive FOBT registry and physician reminder
      system. Navigation included UC plus care coordination and patient self-management
      support from a registered nurse who tracked and assisted patients until they
      completed or refused colonoscopy. The primary outcome was completion of
      colonoscopy within 6 months. After 6 months, both groups received navigation.
      RESULTS: We randomized 147 participants with a positive FOBT or sigmoidoscopy.
      Completion of colonoscopy was higher in the intervention group at 6 months, but
      differences were not statistically significant (91.0% in navigation group vs
      80.8% in UC group; adjusted difference, 10.1%; P = .10). Reasons for no or late
      colonoscopies included refusal, failure to schedule or missed appointments,
      concerns about risks or costs, and competing health concerns. CONCLUSIONS:
      Navigation did not lead to a statistically significant incremental benefit at 6
      months. IMPACT: Follow-up rates after a positive colorectal cancer (CRC)
      screening test are high in a health care system where UC included a registry and
      physician reminders. Because of high follow-up rates in a health care system
      where UC included a registry and physician reminders, and small sample size, we
      cannot rule out incremental benefits of nurse navigation.

PMID- 25381078
TI  - Using geographic information systems (GIS) to identify communities in need of
      health insurance outreach: An OCHIN practice-based research network (PBRN)
      report.
AB  - BACKGROUND: Our practice-based research network (PBRN) is conducting an outreach
      intervention to increase health insurance coverage for patients seen in the
      network. To assist with outreach site selection, we sought an understandable way
      to use electronic health record (EHR) data to locate uninsured patients. METHODS:
      Health insurance information was displayed within a web-based mapping platform to
      demonstrate the feasibility of using geographic information systems (GIS) to
      visualize EHR data. This study used EHR data from 52 clinics in the OCHIN PBRN.
      We included cross-sectional coverage data for patients aged 0 to 64 years with at
      least 1 visit to a study clinic during 2011 (n = 228,284). RESULTS: Our PBRN was
      successful in using GIS to identify intervention sites. Through use of the maps,
      we found geographic variation in insurance rates of patients seeking care in
      OCHIN PBRN clinics. Insurance rates also varied by age: The percentage of adults
      without insurance ranged from 13.2% to 86.8%; rates of children lacking insurance
      ranged from 1.1% to 71.7%. GIS also showed some areas of households with median
      incomes that had low insurance rates. DISCUSSION: EHR data can be imported into a
      web-based GIS mapping tool to visualize patient information. Using EHR data, we
      were able to observe smaller areas than could be seen using only publicly
      available data. Using this information, we identified appropriate OCHIN PBRN
      clinics for dissemination of an EHR-based insurance outreach intervention. GIS
      could also be used by clinics to visualize other patient-level characteristics to
      target clinic outreach efforts or interventions.

PMID- 25381079
TI  - Unrecognized heart failure and chronic obstructive pulmonary disease (COPD) in
      frail elderly detected through a near-home targeted screening strategy.
AB  - BACKGROUND: Reduced exercise tolerance and dyspnea are common in older people,
      and heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the
      main causes. We want to determine the prevalence of previously unrecognized HF,
      COPD, and other chronic diseases in frail older people using a near-home targeted
      screening strategy. METHODS: Community-dwelling frail persons aged >=65 years
      underwent a 2-step screening strategy. First, they received a questionnaire
      inquiring about dyspnea and exercise tolerance. Those with exercise intolerance
      and/or dyspnea were invited to visit their primary care physician's office for a
      screening program, including medical history taking, physical examination, blood
      tests, electrocardiography, spirometry, and echocardiography. The final diagnosis
      of every patient was determined by a panel consisting of 3 physicians. RESULTS:
      Of the 570 elderly who filled out the questionnaire, 395 (69%) had reduced
      exercise tolerance or dyspnea. Of these, 389 underwent the screening program: 127
      (33.5%, 95% confidence interval, 28.9-38.4%) were newly diagnosed with HF (mainly
      HF with a preserved ejection fraction [23.5%]), and previously unrecognized COPD
      was detected in 16.8% (95% confidence interval, 13.4-20.9%). In total, 165
      patients (43.9%) received a new diagnosis of either HF, COPD, or both. Other new
      diagnoses (in 32.7% of the screening program patients) included atrial
      fibrillation (1.8%), valvular disease (21.4%), (persisting) asthma (3.1%), anemia
      (12.7%), and thyroid disease (0.6%). No clear explanation for the complaints of
      47 patients (12.2%) was found using our strategy. CONCLUSION: Unrecognized
      chronic diseases might be detected in community-dwelling frail elderly using a
      near-home screening strategy that is simple to implement. It remains to be
      proven, however, whether optimizing treatment of the newly detected diagnoses in
      this fragile population with multimorbidities and polypharmacy improves quality
      of life and reduces morbidity and mortality.

PMID- 25381080
TI  - Intrauterine devices at six months: does patient age matter? Results from an
      urban family medicine federally qualified health center (FQHC) network.
AB  - BACKGROUND: Federally qualified health centers (FQHCs) can address high rates of
      unintended pregnancy among adolescents in the United States by increasing access
      to intrauterine devices (IUDs) in underserved settings. Despite national
      guidelines endorsing adolescent use of IUDs, some physicians remain concerned
      about IUD tolerance and safety in adolescents. Therefore we compared adolescents
      and adults in a family physician staffed FQHC network with regard to (1) IUD
      postinsertion experience, (2) device discontinuation, and (3) sexually
      transmitted infection (STI) rates. METHODS: We conducted a retrospective cohort
      study among women <36 years old who had an IUD inserted in 2011 at a New York
      City FQHC staffed by family physicians. RESULTS: We included 684 women (27%
      adolescents, 73% adults). During the 6-month postinsertion period, 59% of
      adolescents and 43% of adults initiated IUD-related clinical contact after
      insertion, most commonly for bleeding changes and pelvic or abdominal pain. There
      were no significant differences between groups in IUD expulsion or removal or STI
      rates. CONCLUSIONS: Urban FQHC providers may anticipate that, compared with their
      adult IUD users, adolescents will initiate more clinical follow-up visits after
      insertion. Both groups will, however, have similar clinical concerns about,
      reasons for, and rate of device discontinuation and low STI rates.

PMID- 25381081
TI  - Community-engagement strategies of the developmental disabilities practice-based
      research network (DD-PBRN).
AB  - There is often a rich but untold history of events that occur and relationships
      that form before a practice-based research network (PBRN) is launched. This is
      particularly the case in PBRNs that are community based and comprise partnerships
      outside of the health care system. In this article we summarize an organizational
      "prenatal history" before the birth of a PBRN devoted to people with
      developmental disabilities. Using a case study approach, this article describes
      the historic events that preceded and fostered the evolution of this PBRN and
      contrasts how the processes leading to the creation of this multistakeholder,
      community-based PBRN differ from those of typical academic/clinical practice
      PBRNs. We propose potential advantages and complexities inherent to this newest
      iteration of PBRNs.

PMID- 25381082
TI  - Back to the future: reflections on the history of the future of family medicine.
AB  - These are historic times for family medicine. The profession is moving beyond the
      visionary blueprint of the Future of Family Medicine (FFM) report while working
      to harness the momentum created by the FFM movement. Preparing for, and leading
      through, the next transformative wave of change (FFM version 2.0) will require
      the engagement of multigenerational and multidisciplinary visionaries who bring
      wisdom from diverse experiences. Active group reflection on the past will
      potentiate the collective work being done to best chart the future. Historical
      competency is critically important for family medicine's future. This article
      describes the historical context of the development and launch of the FFM report,
      emphasizing the professional activism that preceded and followed it. This article
      is intended to spark intergenerational dialog by providing a multigenerational
      reflection on the history of FFM and the evolution that has occurred in family
      medicine over the past decade. Such intergenerational conversations enable our
      elders to share wisdom with our youth, while allowing our discipline to visualize
      history through the eyes of future generations.

PMID- 25381083
TI  - Using the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) model in
      clinical research: Application to refine a practice-based research network (PBRN)
      study.
AB  - BACKGROUND: Pragmatic clinical trials (PCTs) are increasingly recommended to
      evaluate interventions in real-world conditions. Although PCTs share a common
      approach of evaluating variables from actual clinical practice, multiple
      characteristics can differ. These differences affect interpretation of the trial.
      The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) model was
      developed in 2009 by the CONSORT Work Group on Pragmatic Trials, published by
      Thorpe et al, to aid in trial design. PRECIS provides clarity about the
      generalizability and applicability of a trial by depicting multiple study
      characteristics. We recently completed a National Institutes of Health-sponsored
      pilot study examining health-related outcomes for 2 complementary therapies for
      chronic low back pain in patients referred by primary care providers in the
      Kentucky Ambulatory Network. In preparation for a larger study, we sought to
      characterize the pragmatic features of the study to aid in our design decisions.
      The purpose of this article is to introduce clinical researchers to the PRECIS
      model while demonstrating its application to refine a practice based research
      network study. METHOD: We designed an exercise using an audience response system
      integrated with a Works in Progress presentation to experienced researchers at
      the University of Kentucky to examine our study methodologies of parameters
      suggested by the PRECIS model. RESULTS: The exercise went smoothly and
      participants remained engaged throughout. The study received an overall summary
      score of 30.17 (scale of 0 to 48; a higher score indicates a more pragmatic
      approach), with component scores that differentiate design components of the
      study. A polar chart is presented to depict the pragmatism of the overall study
      methodology across each of these components. CONCLUSIONS: The study was not as
      pragmatic as expected. The exercise results seem to be useful in identifying
      necessary refinements to the study methodology that may benefit future study
      design and increase generalizability. Readers can identify how the PRECIS model
      may be used to provide clarity and transparency for proposed or existing studies
      and may wish to replicate our exercise in planning their own studies.

PMID- 25381084
TI  - Underinsurance before the implementation of the Affordable Care Act: From the
      Research Involving Outpatient Settings Network (RIOS Net).
AB  - BACKGROUND: As the Affordable Care Act (ACA) is implemented and many uninsured
      become insured, rates of underinsurance may persist or increase. This study was
      designed to estimate the rate of underinsurance in primary care safety net
      clinics serving low income, multiethnic populations in New Mexico. METHODS: Data
      were collected from 2 primary care clinics in an urban setting during a 2-week
      period in 2011 and 2012. Voluntary, anonymous, self-administered surveys were
      distributed to adult patients waiting to be seen by their doctor. Surveys were
      available in English and Spanish. RESULTS: Of those insured, 44% were
      underinsured. The underinsured comprised higher proportions of patients who were
      Hispanic, young, and poor; 39% reported fair or poor health, 23% reported that
      their health suffered from an inability to seek care because of cost, and 53% had
      either Medicaid or state coverage insurance. Patients with an income of <=$25,000
      were 8 times more likely to be underinsured. CONCLUSION: A high level of
      underinsurance was found in these safety net clinics. Because millions of
      Americans gain health care insurance benefits, monitoring whether the current
      reform provides adequate health care coverage or whether those with new and
      existing health care insurance are underinsured is critical.

PMID- 25381089
TI  - New allometric scaling relationships and applications for dose and toxicity
      extrapolation.
AB  - Allometric scaling between metabolic rate, size, body temperature, and other
      biological traits has found broad applications in ecology, physiology, and
      particularly in toxicology and pharmacology. Basal metabolic rate (BMR) was
      observed to scale with body size and temperature. However, the mass scaling
      exponent was increasingly debated whether it should be 2/3, 3/4, or neither, and
      scaling with body temperature also attracted recent attention. Based on
      thermodynamic principles, this work reports 2 new scaling relationships between
      BMR, size, temperature, and biological time. Good correlations were found with
      the new scaling relationships, and no universal scaling exponent can be obtained.
      The new scaling relationships were successfully validated with external
      toxicological and pharmacological studies. Results also demonstrated that
      individual extrapolation models can be built to obtain scaling exponent specific
      to the interested group, which can be practically applied for dose and toxicity
      extrapolations. 

PMID- 25381088
TI  - Mixed methods study of help seekers and self-changers responding to an online
      recovery survey.
AB  - AIMS: To compare self-changers (natural recovery) with help seekers on
      demographics, pre-recovery problem severity, and recovery beliefs and behaviors;
      and to augment these quantitative findings with information extracted from the
      qualitative stories of a subset of self-changers to explore themes in recovery
      paths as informed by a nascent natural recovery literature. METHODS: Quantitative
      secondary analyses were conducted with persons who had responded to a US
      nationwide online survey called 'What Is Recovery' (WIR) and who reported a prior
      lifetime alcohol problem (n = 5495). Six men and six women (with longer-term
      recoveries) interviewed later were asked to tell their 'recovery story from the
      beginning up to now'. These were coded using a narrative approach. RESULTS:
      Compared with help seekers, self-changers were younger and never married: they
      did not differ on problem severity, gender, ethnicity or education. Self-changers
      identified with 'used to have a problem' more than in recovery/recovered,
      reported fewer years in that status, and reported more current, non-problematic
      substance use. A new concept of shadow help and shadow obstacles to help-seeking
      emerged from the qualitative analysis. Though self-changers believed that they
      had overcome their alcohol problem on their own, change actually occurred within
      a social context that allowed access to information, normative expectations,
      relationships, and other opportunities that provided important resources for
      change. CONCLUSION: Findings imply that the concept of help-seeking needs to be
      re-conceptualized to include the informal help we found in this study.

PMID- 25381090
TI  - Correlation of cardiac output measured by non-invasive continuous cardiac output
      monitoring (NICOM) and thermodilution in patients undergoing off-pump coronary
      artery bypass surgery.
AB  - PURPOSE: This observational study was designed to evaluate the clinical value of
      cardiac output (CO) obtained via bioreactance (NICOMTM) as compared with values
      of CO obtained via thermodilution (using pulmonary artery catheter, VigilanceTM)
      and the thoracic bioimpedance (BioZ.comTM), in patients undergoing off-pump
      coronary artery bypass surgery. METHODS: Fifty American Society of
      Anesthesiologists physical status I-III patients, aged 38-81 years, scheduled for
      off-pump coronary artery bypass surgery were enrolled in this study. CO data
      (NCO, BCO, PCO) were recorded during the operative period at ten time points
      after stable hemodynamic conditions were achieved. RESULTS: The equation of the
      relationship between the PCO and NCO is PCO = 0.945 * NCO + 0.328 (r = 0.77), and
      that of PCO and BCO is PCO = 0.965 * BCO + 0.729 (r = 0.63). Furthermore, no
      statistical difference was found between PCO versus NCO (mean (SD): 4.4 (1.1)
      versus 4.4 (0.9), p = 0.431). A significant correlation was found between PCO and
      NCO (r = 0.77, p < 0.001). Correlation was also found between PCO and BCO (r =
      0.63, p < 0.001). CONCLUSIONS: The NICOM device is a safe, convenient, and
      reliable device for measuring continuous non-invasive cardiac output and cardiac
      index, and the trends of change in CO during the surgery are similar between
      NICOM and PAC.

PMID- 25381091
TI  - Whole exome sequencing reveals novel COL4A3 and COL4A4 mutations and resolves
      diagnosis in Chinese families with kidney disease.
AB  - BACKGROUND: Collagen IV-related nephropathies, including thin basement membrane
      nephropathy and Alport Syndrome (AS), are caused by defects in the genes COL4A3,
      COL4A4 and COL4A5. Diagnosis of these conditions can be hindered by variable
      penetrance and the presence of non-specific clinical or pathological features.
      METHODS: Three families with unexplained inherited kidney disease were recruited
      from Shanghai, China. Whole exome sequencing (WES) was performed in the index
      case from each family and co-segregation of candidate pathogenic mutations was
      tested by Sanger sequencing. RESULTS: We identified COL4A4 missense variants
      [c.G2636A (p.Gly879Glu) and c.C4715T (p.Pro1572Leu)] in the 21-year-old male
      proband from family 1, who had been diagnosed with mesangial proliferative
      nephropathy at age 14. COL4A4 c.G2636A, a novel variant, co-segregated with renal
      disease among maternal relatives. COL4A4 c.C4715T has previously been associated
      with autosomal recessive AS and was inherited from his clinically unaffected
      father. In family 2, a novel COL4A3 missense mutation c.G2290A (p.Gly997Glu) was
      identified in a 45-year-old male diagnosed with focal segmental
      glomerulosclerosis and was present in all his affected family members, who
      exhibited disease ranging from isolated microscopic hematuria to end stage renal
      disease (ESRD). In family 3, ESRD occurred in both male and females who were
      found to harbor a known AS-causing COL4A5 donor splice site mutation
      (c.687+1G>A). None of these variants were detected among 100 healthy Chinese
      individuals. CONCLUSION: WES identified 2 novel and 2 known pathogenic
      COL4A3/COL4A4/COL4A5 mutations in 3 families with previously unexplained
      inherited kidney disease. These findings highlight the clinical range of collagen
      IV-related nephropathies and resolved diagnostic confusion arising from atypical
      or incomplete clinical/histological findings, allowing appropriate counselling
      and treatment advice to be given.

PMID- 25381092
TI  - Stress thallium-201/rest technetium-99m sequential dual-isotope high-speed
      myocardial perfusion imaging validation versus invasive coronary angiography.
AB  - BACKGROUND: Recent advances in nuclear myocardial perfusion imaging (MPI) have
      made it possible to develop a dual-isotope protocol for high-speed acquisition
      with image quality and radiation delivery comparable to that obtained with
      conventional single isotope protocols. So far, no study has compared dual-isotope
      high-speed MPI to invasive coronary angiography (ICA) in a large cohort using a
      Cadmium-zinc-telluride SPECT system. METHODS: Over a 1-year period (May 2011 to
      April 2012), 1366 patients underwent dual-isotope high-speed MPI. Patients with
      ICA within 3 months after dual-isotope high-speed MPI were included together with
      patients with a low likelihood of coronary artery disease (CAD) in order to
      assess normalcy rate. Global summed stress score (SSS) and summed rest score
      (SRS) were calculated, and ICA results were analyzed independently. The main end
      point was a patient-based assessment of the diagnostic performance of dual
      isotope high-speed MPI in detecting or ruling out significant CAD (>70% reduction
      in lumen diameter). RESULTS: Inclusion criteria were fulfilled for 214 patients
      (143 men; age 60 +/- 14 years; ICA, n = 104; low likelihood for CAD, n = 110). An
      exercise stress test was performed in 62% of patients and a pharmacological
      stress test was performed with either dipyridamole (32%) or dobutamine (6%).
      Average examination duration was 22.4 +/- 4.5 minutes. Mean SSS, SRS, and SDS
      were 8.0 +/- 4.9, 3.1 +/- 4.3, and 5.0 +/- 3.2, respectively. Prevalence of
      angiographic CAD was 75%. ICA detected stenosis in the left main trunk, left
      anterior descending artery, left circumflex artery, and right coronary artery in
      4, 33, 31, and 42 patients, respectively. Sensitivity of dual-isotope high-speed
      MPI was 94%, normalcy rate was 92%, and accuracy was 83% for detecting CAD.
      CONCLUSION: Dual-isotope high-speed MPI is reliable at detecting or ruling out
      CAD. NCT01785589.

PMID- 25381093
TI  - Clinically stable very low birthweight infants are at risk for recurrent tissue
      glucose fluctuations even after fully established enteral nutrition.
AB  - OBJECTIVE: In previous cases, we have observed occasional hypoglycaemic episodes
      in preterm infants after initial intensive care. In this prospective study, we
      determined the frequency and severity of abnormal tissue glucose (TG) in
      clinically stable preterm infants on full enteral nutrition. METHODS: Preterm
      infants born at <1000 g (n=23; G1) and birth weight 1000-1500 g (n=18; G2) were
      studied at a postmenstrual age of 32+/-2 weeks (G1) and 33+/-2 weeks (G2).
      Infants were fed two or three hourly, according to a standard bolus-nutrition
      protocol, and continuous subcutaneous glucose measurements were performed for 72
      h. Normal glucose values were assumed at >=2.5 mmol/L (45 mg/dL) and <=8.3 mmol/L
      (150 mg/dL). Frequency, severity and duration of glucose values beyond normal
      values were determined. RESULTS: We observed asymptomatic low TG values in 39% of
      infants in G1 and in 44% in G2. High TG values were detected in 83% in G1 and 61%
      in G2. Infants in G1 experienced prolonged and more severe low TG episodes, and
      also more frequent and severe high TG episodes. In G1 and G2, 87% and 67% of the
      infants, respectively, showed glucose fluctuations characterised by rapid glucose
      increase followed by a rapid glucose drop after feeds. In more mature infants,
      glucose fluctuations were less pronounced and less dependent on enteral feeds.
      CONCLUSIONS: Clinically stable well-developing preterm infants beyond their
      initial period of intensive care show interstitial glucose instabilities
      exceeding values as low as 2.5 mmol/L and as high as 8.3 mmol/L. This novel
      observation may play an important role for the susceptibility of these high-risk
      infants for the development of the metabolic syndrome. TRIAL REGISTRATION NUMBER:
      German trial registration number DRKS00004590.

PMID- 25381094
TI  - Great auricular nerve preservation in parotid surgery: rationale and long-term
      results insights.
AB  - Great auricular nerve (GAN) is frequently sacrificed during parotid surgery. GAN
      preservation during parotidectomy is advised to avoid complications such as
      sensitive disorders, but debate still exists. In this study, our experience is
      reported on the matter. From a cohort of 173 parotidectomies carried out in the
      period 2005-2010, we studied 60 patients: 20 patients in which we preserved only
      the posterior branch of GAN (group A), 20 patients in which we preserved also the
      lobular branch (group B) and 20 patients in which the main trunk of GAN was
      sectioned (group C); we evaluated tactile sensitivity in all the skin supplied by
      GAN at 1 week, 1 month, 6 months and 1 year after surgery. Group B is the best in
      terms of loss and recovery of sensitivity after 1-year post-surgery, followed
      closely by group A, on the contrary group C confirmed to be the worst. Results
      suggest that saving as many branches of the GAN as possible during parotid
      surgery could be useful for reducing hypo-dysesthesia. Preserving posterior and
      lobular branches of the GAN, when possible, improves the sensitivity of the
      preauricular area with better quality of life for the patient.

PMID- 25381095
TI  - Pharyngolateral ferromagnetic prosthesis (PFP) for treatment of obstructive sleep
      apnea.

PMID- 25381096
TI  - Prospective clinical study on long-term swallowing function and voice quality in
      advanced head and neck cancer patients treated with concurrent chemoradiotherapy
      and preventive swallowing exercises.
AB  - Concurrent chemoradiotherapy (CCRT) for advanced head and neck cancer (HNC) is
      associated with substantial early and late side effects, most notably regarding
      swallowing function, but also regarding voice quality and quality of life (QoL).
      Despite increased awareness/knowledge on acute dysphagia in HNC survivors, long
      term (i.e., beyond 5 years) prospectively collected data on objective and
      subjective treatment-induced functional outcomes (and their impact on QoL) still
      are scarce. The objective of this study was the assessment of long-term CCRT
      induced results on swallowing function and voice quality in advanced HNC
      patients. The study was conducted as a randomized controlled trial on preventive
      swallowing rehabilitation (2006-2008) in a tertiary comprehensive HNC center with
      twenty-two disease-free and evaluable HNC patients as participants.
      Multidimensional assessment of functional sequels was performed with
      videofluoroscopy, mouth opening measurements, Functional Oral Intake Scale,
      acoustic voice parameters, and (study specific, SWAL-QoL, and VHI)
      questionnaires. Outcome measures at 6 years post-treatment were compared with
      results at baseline and at 2 years post-treatment. At a mean follow-up of 6.1
      years most initial tumor-, and treatment-related problems remained similarly low
      to those observed after 2 years follow-up, except increased xerostomia (68%) and
      increased (mild) pain (32%). Acoustic voice analysis showed less voicedness,
      increased fundamental frequency, and more vocal effort for the tumors located
      below the hyoid bone (n = 12), without recovery to baseline values. Patients'
      subjective vocal function (VHI score) was good. Functional swallowing and voice
      problems at 6 years post-treatment are minimal in this patient cohort,
      originating from preventive and continued post-treatment rehabilitation programs.

PMID- 25381097
TI  - Changes and recovery of voice quality after sinonasal surgery.
AB  - Changes in the configuration of sinonasal cavity after surgery have been assumed
      to cause changes in the voice quality. The purpose of this study was to know when
      the hypernasality will be recovered after sinonsal surgery in patients with nasal
      septal deviation or chronic rhinosinusitis by checking long-term and serially
      obtained nasalance scores using nasometer. Sixty-five patients underwent
      sinonasal surgery were included. We classified the subjects into three groups
      according to the different surgical interventions employed: septoplasty group,
      endoscopic sinus surgery (ESS) group, and ESS with septoplasty group. The
      nasalance scores were obtained using a nasometer preoperatively, 1, 2, 3, 4, 5,
      and 6 months after surgery. The mean nasalance scores for vowels, nasal
      consonant, plosive consonant-vowel combinations, nasal consonant-vowel
      combinations, a hypernasality sentence, and hyponasality sentence increased
      significantly after sinonasal surgery. Hypernasality was most prominent in all
      groups for all acoustic parameters 1 month after surgery. Thereafter nasality
      decreased and returned to its preoperative level in all groups at 5 months in the
      [m], [ma], [mi], and hypernasality sentence, but at 6 months in the [a], [i],
      [u], [p(h)a], [p(h)i], and hyponasality sentence. Sinonasal surgery can change
      the acoustic characteristics of the vocal tract and produce a significant
      increase in nasality. After nasality showed the highest scores at 1-month post
      surgery, it returned to its preoperative level at 5 or 6 months after surgery
      depending on the subtype of speech stimuli.

PMID- 25381098
TI  - Current treatment of T1N0 squamous cell carcinoma of the glottic larynx.

PMID- 25381099
TI  - Visual analytics of signalling pathways using time profiles.
AB  - Data visualisation is usually a crucial first step in analysing and exploring
      large-scale complex data. The visualisation of proteomics time-course data on
      post-translational modifications presents a particular challenge that is largely
      unmet by existing tools and methods. To this end, we present Minardo, a novel
      visualisation strategy tailored for such proteomics data, in which data layout is
      driven by both cellular topology and temporal order. In this work, we utilised
      the Minardo strategy to visualise a dataset showing phosphorylation events in
      response to insulin. We evaluated the visualisation together with experts in
      diabetes and obesity, which led to new insights into the insulin response
      pathway. Based on this success, we outline how this layout strategy could be
      automated into a web-based tool for visualising a broad range of proteomics time
      course data. We also discuss how the approach could be extended to include
      protein 3D structure information, as well as higher dimensional data, such as a
      range of experimental conditions. We also discuss our entry of Minardo in the
      international DREAM8 competition. 

PMID- 25381100
TI  - Modeling of testosterone regulation by pulse-modulated feedback.
AB  - The continuous part of a hybrid (pulse-modulated) model of testosterone (Te)
      feedback regulation in the human male is extended with infinite-dimensional and
      nonlinear blocks, to obtain the dynamics that better agree with the hormone
      concentration profiles observed in clinical data. A linear least-squares based
      optimization algorithm is developed for the purpose of detecting impulses of
      gonadotropin-releasing hormone (GnRH) from measured concentration of luteinizing
      hormone (LH). The estimated impulse parameters are instrumental in evaluating the
      frequency and amplitude modulation functions parameterizing the pulse-modulated
      feedback. The proposed approach allows for the identification of all model
      parameters from the hormone concentrations of Te and LH. Simulation results of
      the complete estimated closed-loop system exhibiting similar to the clinical data
      behavior are provided. 

PMID- 25381101
TI  - Hybrid algorithms for multiple change-point detection in biological sequences.
AB  - Array comparative genomic hybridization (aCGH) is one of the techniques that can
      be used to detect copy number variations in DNA sequences in high resolution. It
      has been identified that abrupt changes in the human genome play a vital role in
      the progression and development of many complex diseases. In this study we
      propose two distinct hybrid algorithms that combine efficient sequential change
      point detection procedures (the Shiryaev-Roberts procedure and the cumulative sum
      control chart (CUSUM) procedure) with the Cross-Entropy method, which is an
      evolutionary stochastic optimization technique to estimate both the number of
      change-points and their corresponding locations in aCGH data. The proposed hybrid
      algorithms are applied to both artificially generated data and real aCGH
      experimental data to illustrate their usefulness. Our results show that the
      proposed methodologies are effective in detecting multiple change-points in
      biological sequences of continuous measurements. 

PMID- 25381102
TI  - Stochastic anomaly detection in eye-tracking data for quantification of motor
      symptoms in Parkinson's disease.
AB  - Two methods for distinguishing between healthy controls and patients diagnosed
      with Parkinson's disease by means of recorded smooth pursuit eye movements are
      presented and evaluated. Both methods are based on the principles of stochastic
      anomaly detection and make use of orthogonal series approximation for probability
      distribution estimation. The first method relies on the identification of a
      Wiener model of the smooth pursuit system and attempts to find statistically
      significant differences between the estimated parameters in healthy controls and
      patients with Parkinson's disease. The second method applies the same statistical
      method to distinguish between the gaze trajectories of healthy and Parkinson
      subjects tracking visual stimuli. Both methods show promising results, where
      healthy controls and patients with Parkinson's disease are effectively separated
      in terms of the considered metric. The results are preliminary because of the
      small number of participating test subjects, but they are indicative of the
      potential of the presented methods as diagnosing or staging tools for Parkinson's
      disease. 

PMID- 25381103
TI  - Identification of the Reichardt elementary motion detector model.
AB  - The classical Hassenstein-Reichardt mathematical elementary motion detector (EMD)
      model is treated analytically. The EMD is stimulated with drifting sinusoidal
      gratings, which are often used in motion vision research, thus enabling direct
      comparison with neural responses from motion-sensitive neurones in the fly brain.
      When sinusoidal gratings are displayed on a cathode ray tube monitor, they are
      modulated by the refresh rate of the monitor. This generates a pulsatile
      signature of the visual stimulus, which is also seen in the neural response. Such
      pulsatile signals make a Laguerre domain identification method for estimating the
      parameters of a single EMD suitable, allowing estimation of both finite and
      infinite-dimensional dynamics. To model the response of motion-sensitive neurones
      with large receptive fields, a pool of spatially distributed EMDs is considered,
      with the weights of the contributing EMDs fitted to the neural data by a sparse
      estimation method. Such an EMD-array is more reliably estimated by stimulating
      with multiple sinusoidal gratings, since these provide higher spatial excitation
      than a single sinusoidal grating. Consequently, a way of designing the visual
      stimuli for a certain order of spatial resolution is suggested. 

PMID- 25381104
TI  - Multi-complexity ensemble measures for gait time series analysis: application to
      diagnostics, monitoring and biometrics.
AB  - Previously, we have proposed to use complementary complexity measures discovered
      by boosting-like ensemble learning for the enhancement of quantitative indicators
      dealing with necessarily short physiological time series. We have confirmed
      robustness of such multi-complexity measures for heart rate variability analysis
      with the emphasis on detection of emerging and intermittent cardiac
      abnormalities. Recently, we presented preliminary results suggesting that such
      ensemble-based approach could be also effective in discovering universal meta
      indicators for early detection and convenient monitoring of neurological
      abnormalities using gait time series. Here, we argue and demonstrate that these
      multi-complexity ensemble measures for gait time series analysis could have
      significantly wider application scope ranging from diagnostics and early
      detection of physiological regime change to gait-based biometrics applications. 

PMID- 25381105
TI  - Development of a motion capturing and load analyzing system for caregivers aiding
      a patient to sit up in bed.
AB  - This research was carried out to analyze the actions of caregivers when aiding a
      patient to sit up in bed. The new system showed that three dimensional analysis
      could be performed even on points on the subjects' bodies that were hidden from
      view. We also developed a method to estimate the load on the lumbar region of
      caregivers based on the kinetic analysis of the human body. Using this system we
      were able to evaluate the performance of both lay and professional caregivers. We
      found a clear difference between the performances of the two types of caregivers,
      and noted that the professional adopted a posture that was safe and did not
      stress the lumbar vertebrae, whereas the layperson tended to adopt an unsafe
      posture. 

PMID- 25381106
TI  - Classifying epileptic EEG signals with delay permutation entropy and Multi-Scale
      K-means.
AB  - Most epileptic EEG classification algorithms are supervised and require large
      training datasets, that hinder their use in real time applications. This chapter
      proposes an unsupervised Multi-Scale K-means (MSK-means) MSK-means algorithm to
      distinguish epileptic EEG signals and identify epileptic zones. The random
      initialization of the K-means algorithm can lead to wrong clusters. Based on the
      characteristics of EEGs, the MSK-means MSK-means algorithm initializes the coarse
      scale centroid of a cluster with a suitable scale factor. In this chapter, the
      MSK-means algorithm is proved theoretically superior to the K-means algorithm on
      efficiency. In addition, three classifiers: the K-means, MSK-means MSK-means and
      support vector machine (SVM), are used to identify seizure and localize
      epileptogenic zone using delay permutation entropy features. The experimental
      results demonstrate that identifying seizure with the MSK-means algorithm and
      delay permutation entropy achieves 4. 7 % higher accuracy than that of K-means,
      and 0. 7 % higher accuracy than that of the SVM. 

PMID- 25381107
TI  - Tracking of EEG activity using motion estimation to understand brain wiring.
AB  - The fundamental step in brain research deals with recording electroencephalogram
      (EEG) signals and then investigating the recorded signals quantitatively.
      Topographic EEG (visual spatial representation of EEG signal) is commonly
      referred to as brain topomaps or brain EEG maps. In this chapter, full search
      full search block motion estimation algorithm has been employed to track the
      brain activity in brain topomaps to understand the mechanism of brain wiring. The
      behavior of EEG topomaps is examined throughout a particular brain activation
      with respect to time. Motion vectors are used to track the brain activation over
      the scalp during the activation period. Using motion estimation it is possible to
      track the path from the starting point of activation to the final point of
      activation. Thus it is possible to track the path of a signal across various
      lobes. 

PMID- 25381108
TI  - Towards automated quantitative vasculature understanding via ultra high
      resolution imagery.
AB  - This chapter presents an approach to processing ultra high-resolution, large-size
      biomedical imaging data for the purposes of detecting and quantifying vasculature
      and microvasculature . Capturing early signs of any changes in vasculature may
      have significant values for early-diagnosis and treatment assessment due to the
      well understood observation that vascular changes precede cancerous growth and
      metastasis metastasis . With the advent of key enabling technologies for
      extremely high-resolution imaging, such as synchrotron radiation synchrotron
      radiation based computed tomography (CT) computed tomography , the required
      levels of detail have become accessible. However, these technologies also present
      challenges in data analysis. This chapter aims to offer some insights as to how
      these changes might be best dealt with. We argue that the necessary steps in
      quantitative understanding of vasculatures include targeted data enhancement
      enhancement , information reduction aimed at characterizing the linear structure
      of vessels vessels , and quantitatively describing the vessel hierarchy. We
      present results on cerebral and liver vasculatures of a mouse captured at the
      Shanghai Synchrotron Radiation Facility (SSRF). These results were achieved with
      a processing pipeline comprising of our empirically selected component for each
      of the above steps. Towards the end, we discuss how alternative and additional
      components may be incorporated for improved speed and robustness.

PMID- 25381109
TI  - Cloud based toolbox for image analysis, processing and reconstruction tasks.
AB  - This chapter describes a novel way of carrying out image analysis, reconstruction
      and processing tasks using cloud based service provided on the Australian
      National eResearch Collaboration Tools and Resources (NeCTAR) infrastructure. The
      toolbox allows users free access to a wide range of useful blocks of
      functionalities (imaging functions) that can be connected together in workflows
      allowing creation of even more complex algorithms that can be re-run on different
      data sets, shared with others or additionally adjusted. The functions given are
      in the area of cellular imaging, advanced X-ray image analysis, computed
      tomography and 3D medical imaging and visualisation. The service is currently
      available on the website www.cloudimaging.net.au . 

PMID- 25381110
TI  - Pollen image classification using the Classifynder system: algorithm comparison
      and a case study on New Zealand honey.
AB  - We describe an investigation into how Massey University's Pollen Classifynder can
      accelerate the understanding of pollen and its role in nature. The Classifynder
      is an imaging microscopy system that can locate, image and classify slide based
      pollen samples. Given the laboriousness of purely manual image acquisition and
      identification it is vital to exploit assistive technologies like the
      Classifynder to enable acquisition and analysis of pollen samples. It is also
      vital that we understand the strengths and limitations of automated systems so
      that they can be used (and improved) to compliment the strengths and weaknesses
      of human analysts to the greatest extent possible. This article reviews some of
      our experiences with the Classifynder system and our exploration of alternative
      classifier models to enhance both accuracy and interpretability. Our experiments
      in the pollen analysis problem domain have been based on samples from the
      Australian National University's pollen reference collection (2,890 grains, 15
      species) and images bundled with the Classifynder system (400 grains, 4 species).
      These samples have been represented using the Classifynder image feature set. We
      additionally work through a real world case study where we assess the ability of
      the system to determine the pollen make-up of samples of New Zealand honey. In
      addition to the Classifynder's native neural network classifier, we have
      evaluated linear discriminant, support vector machine, decision tree and random
      forest classifiers on these data with encouraging results. Our hope is that our
      findings will help enhance the performance of future releases of the Classifynder
      and other systems for accelerating the acquisition and analysis of pollen
      samples. 

PMID- 25381111
TI  - Digital image processing and analysis for activated sludge wastewater treatment.
AB  - Activated sludge system is generally used in wastewater treatment plants for
      processing domestic influent. Conventionally the activated sludge wastewater
      treatment is monitored by measuring physico-chemical parameters like total
      suspended solids (TSSol), sludge volume index (SVI) and chemical oxygen demand
      (COD) etc. For the measurement, tests are conducted in the laboratory, which take
      many hours to give the final measurement. Digital image processing and analysis
      offers a better alternative not only to monitor and characterize the current
      state of activated sludge but also to predict the future state. The
      characterization by image processing and analysis is done by correlating the time
      evolution of parameters extracted by image analysis of floc and filaments with
      the physico-chemical parameters. This chapter briefly reviews the activated
      sludge wastewater treatment; and, procedures of image acquisition, preprocessing,
      segmentation and analysis in the specific context of activated sludge wastewater
      treatment. In the latter part additional procedures like z-stacking, image
      stitching are introduced for wastewater image preprocessing, which are not
      previously used in the context of activated sludge. Different preprocessing and
      segmentation techniques are proposed, along with the survey of imaging procedures
      reported in the literature. Finally the image analysis based morphological
      parameters and correlation of the parameters with regard to monitoring and
      prediction of activated sludge are discussed. Hence it is observed that image
      analysis can play a very useful role in the monitoring of activated sludge
      wastewater treatment plants. 

PMID- 25381112
TI  - A complete system for 3D reconstruction of roots for phenotypic analysis.
AB  - Here we present a complete system for 3D reconstruction of roots grown in a
      transparent gel medium or washed and suspended in water. The system is capable of
      being fully automated as it is self calibrating. The system starts with detection
      of root tips in root images from an image sequence generated by a turntable
      motion. Root tips are detected using the statistics of Zernike moments on image
      patches centred on high curvature points on root boundary and Bayes
      classification rule. The detected root tips are tracked in the image sequence
      using a multi-target tracking algorithm. Conics are fitted to the root tip
      trajectories using a novel ellipse fitting algorithm which weighs the data points
      by its eccentricity. The conics projected from the circular trajectory have a
      complex conjugate intersection which are image of the circular points. Circular
      points constraint the image of the absolute conics which are directly related to
      the internal parameters of the camera. The pose of the camera is computed from
      the image of the rotation axis and the horizon. The silhouettes of the roots and
      camera parameters are used to reconstruction the 3D voxel model of the roots. We
      show the results of real 3D reconstruction of roots which are detailed and
      realistic for phenotypic analysis. 

PMID- 25381113
TI  - The relationship of parental rearing behavior and resilience as well as
      psychological symptoms in a representative sample.
AB  - BACKGROUND: Recalled parental rearing behavior is one of the factors influencing
      the strength of resilience. However, it is unclear whether resilience is a
      relatively stable personality trait or has a relational character whose
      protective strength changes over the course of life. Therefore, the association
      between recalled parental rearing and resilience as well as symptoms of anxiety
      and depression was investigated in respect to age and gender. METHODS: N = 4,782
      healthy subjects aged 14-92 (M = 48.1 years) were selected by the random-route
      sampling method. In this sample, an ultra-short form of the Recalled Parental
      Rearing Behavior Questionnaire, the German short version of the resilience scale,
      and two screening instruments for depression and anxiety (PHQ-2, GAD-2) were
      filled out. Structural equation modelling was used to analyze the data estimated
      with the maximum likelihood method approach. RESULTS: The data revealed that
      rejection and punishment were clearly associated with lower resilience. Moreover,
      resilience had a strong connection to the symptoms of anxiety and depression.
      Resilience had the same quality of association in both men and women with respect
      to anxiety and depression. Furthermore, the effect of resilience did not vary
      across several age groups even though challenges may differ over a lifetime.
      CONCLUSION: Recalled parental rearing behavior such as rejection and punishment
      as well as control and overprotection exert a significant association on the
      strength of resilience. Resilience has an effect independent of gender and does
      not affect people of different age groups differently.

PMID- 25381115
TI  - Symptomatic marginal ulcer disease after Roux-en-Y gastric bypass: incidence,
      risk factors and management.
AB  - BACKGROUND: One of the long-term complications of laparoscopic Roux-and-Y gastric
      bypass (LRYGB) is the development of marginal ulcers (MU). The aim of the present
      study is to assess the incidence, risk factors, symptomatology and management of
      patients with symptomatic MU after LRYGB surgery. METHODS: A consecutive series
      of patients who underwent a LRYGB from 2006 until 2011 were evaluated in this
      study. Signs of abdominal pain, pyrosis, nausea or other symptoms of ulcer
      disease were analysed. Acute symptoms of (perforated) MU such as severe abdominal
      pain, vomiting, melena and haematemesis were also collected. Patient baseline
      characteristics, medication and intoxications were recorded. Statistical analysis
      was performed to identify risk factors associated with MU. RESULTS: A total of
      350 patients underwent a LRYGB. Minimal follow-up was 24 months. Twenty-three
      patients (6.6%) developed a symptomatic MU of which four (1.1%) presented with
      perforation. Smoking, the use of corticosteroids and non-steroidal anti
      inflammatory drugs (NSAIDs) was significantly associated with the development of
      MU. Five out of 23 patients (22%) underwent surgery. All other patients could be
      treated conservatively. CONCLUSIONS: Marginal ulcers occurred in 6.6% of the
      patients after a LRYGB. Smoking, the use of corticosteroids and the use of NSAIDs
      were associated with an increased risk of MU. Most patients were managed
      conservatively.

PMID- 25381114
TI  - Parental migration and Asperger's syndrome.
AB  - Parental immigration has been suggested as a possible risk factor for autism
      spectrum disorders (ASD), but findings have been inconsistent. Very few studies
      have focused specifically on Asperger's syndrome. The aim of this study was to
      examine the association between maternal and paternal immigration and the
      diagnosis of Asperger's syndrome in offspring. The study was a nested case
      control study based on a national birth cohort in Finland. Children born in 1987
      2005 and diagnosed with Asperger's syndrome by the year 2007 were identified from
      the Finnish Hospital Discharge Register (N = 1,783). Four matched controls for
      each case were selected from the Finnish Medical Birth Register (N = 7,106).
      Information on maternal and paternal country of birth and mother tongue was
      collected from the Finnish Central Population Register. The study showed that
      children whose parents are both immigrants have a significantly lower likelihood
      of being diagnosed with Asperger's syndrome than those with two Finnish parents
      [adjusted odds ratio (aOR) 0.2, 95 % confidence interval (CI) 0.1-0.4]. No
      significant associations were found between having only one immigrant parent and
      the diagnosis of Asperger's syndrome. A regional analysis showed a significantly
      decreased likelihood of the diagnosis of Asperger's syndrome in children whose
      mother (aOR 0.1, 95 % CI 0.01-0.5) or father (aOR 0.2, 95 % CI 0.05-0.5) was born
      in Sub-Saharan Africa. The findings may help in identifying risk factors for
      different ASD subtypes. On the other hand, they might reflect service use of
      immigrant families in Finland.

PMID- 25381116
TI  - Does somatostatin-14 have an impact on gastric fistula after laparoscopic sleeve
      gastrectomy?
AB  - The main complications following laparoscopic sleeve gastrectomy (LSG) is gastric
      fistula (GF). Gastric fistula is a rare but serious complication (affecting 2 %
      of LSGs). Somatostatin-14 and its analogs are mainly used in the prevention and
      curative treatment of digestive fistulas. These compounds inhibit secretions in
      the pancreas, stomach, and small intestine. Treatment with somatostatin-14
      increases the spontaneous closure rate and reduces the closure time of
      postoperative digestive fistulas. However, the impact of somatostatin-14 on GF
      after LSG has not been studied. We report on a prospective, non-randomized,
      single-center, case-matched study of patients receiving somatostatin-14 after a
      post-LSG GF was discovered. Our results suggest that use of somatostatin-14 is
      associated with a shorter length of hospital stay and (perhaps) a shorter
      treatment period.

PMID- 25381117
TI  - Effects of Roux-en-Y gastric bypass surgery on visceral and subcutaneous fat
      density by computed tomography.
AB  - We aimed to test the hypothesis that noninvasive fat density by computed
      tomography (CT) increases after Roux-en-Y gastric bypass (RYGB) and correlates
      with improved cardiometabolic risk. We examined 21 obese adults before and 12
      months after RYGB and 16 obese nonsurgical controls followed for 12 months.
      Visceral (VAT) and subcutaneous adipose tissue (SAT) density increased after RYGB
      (P < 0.0001) while remaining stable in controls (P >= 0.1). In RYGB subjects, 12
      month increase in VAT density correlated with decreased C-reactive protein (CRP)
      independent of change in VAT area or BMI (both P < 0.05). Twelve-month increase
      in SAT density correlated with increased HDL cholesterol independent of change in
      SAT area (P = 0.048), BMI (P = 0.03), or statin use (P = 0.002), and 1 unit
      increase in SAT density had increased odds of higher total abdominal fat loss (P
      = 0.002).

PMID- 25381118
TI  - Effect of Roux-en-Y gastric bypass on nonalcoholic fatty liver disease evaluated
      through NAFLD fibrosis score: a prospective study.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common among subjects who
      undergo bariatric surgery and its postsurgical improvement has been reported.
      This study aimed to determine the evolution of liver disease evaluated through
      NAFLD fibrosis score 12 months after surgery. METHODS: It is a prospective cohort
      study which evaluated patients immediately before and 12 months following Roux-en
      Y gastric bypass (RYGB). RESULTS: Mean score decreased from 1.142 to 0.066;
      surgery led to a resolution rate of advanced fibrosis of 55 %. Resolution was
      statistically associated with female gender, percentage of excess weight loss,
      postsurgical body mass index, postsurgical platelet count, and diabetes
      resolution. CONCLUSIONS: As previously reported by studies in which postsurgical
      biopsies were performed, RYGB leads to a great resolution rate of liver fibrosis.
      Since postsurgical biopsy is not widely available and has a significant risk,
      calculation of NAFLD fibrosis score is a simple tool to evaluate this evolution
      through a noninvasive approach.

PMID- 25381119
TI  - Post-operative psychosocial predictors of outcome in bariatric surgery.
AB  - Although there are several recent reviews of the pre-operative factors that
      influence treatment outcome for bariatric surgery, commensurate efforts to
      identify and review the predictive validity of post-operative variables are
      lacking. This review describes the post-operative psychosocial predictors of
      weight loss in bariatric surgery. Results suggest empirical support for post
      operative binge eating, uncontrolled eating/grazing, and presence of a depressive
      disorder as negative predictors of weight loss outcomes; whereas, adherence to
      dietary and physical activity guidelines emerged as positive predictors of weight
      loss. With the exception of depression, psychological comorbidities were not
      consistently associated with weight loss outcomes. Results highlight the need for
      post-operative assessment of disordered eating and depressive disorder, further
      research on the predictive value of post-operative psychosocial factors, and
      development of targeted interventions. 

PMID- 25381120
TI  - Effects of omega-loop gastric bypass on vitamin D and bone metabolism in morbidly
      obese bariatric patients.
AB  - BACKGROUND: Bariatric patients often suffer from nutrient deficiencies. Little is
      known about vitamin D levels and bone metabolism in patients undergoing omega
      loop gastric bypass (OLGB). We, therefore, evaluated parameters of vitamin D
      metabolism preoperatively and during the first postoperative year. METHODS:
      Within our cohort study, we retrospectively evaluated the respective parameters
      pre-, 3, 6, and 12 months postoperatively in patients with OLGB, between February
      2011 and February 2013. RESULTS: In patients [n = 50; age 46 (15) years, mean
      (SD); 12 male, 38 female] BMI was 45.4 (6.6) kg/m(2) preoperatively and decreased
      to 29.1 (3.8) kg/m(2) after 12 months, corresponding to a total body weight loss
      of 36 %. Preoperatively, the prevalence of vitamin D deficiency was 96 and 30 %
      demonstrated elevated parathyroid hormone yielding a prevalence of secondary
      hyperparathyroidism of 17 %. Postoperatively, subjects received individually
      adjusted vitamin D3 supplementation (95 % CI 200-3000 IU/day), according to the
      available guidelines at that time. Nevertheless, every third patient was vitamin
      D deficient at 12 months (80 %). In patients with preoperative BMI >45 vs. <45
      kg/m(2), we observed a 3-fold higher risk for vitamin D deficiency over 12 months
      [OR = 3.10, 95 % CI (1.01-9.51), p = 0.048]. CONCLUSIONS: To avoid vitamin D
      deficiency, morbidly obese patients, particularly those with higher preoperative
      BMI, should be regularly screened pre- and postoperatively. Standard postsurgical
      supplementation has not been adequate to restore 25-OHD status and current
      guidelines are not very specific in terms of timing and dosing of vitamin D3
      supplementation. Consequently, further trials to enhance the evidence on vitamin
      D supplementation are warranted.

PMID- 25381121
TI  - Validation of the Care-Related Quality of Life Instrument in different study
      settings: findings from The Older Persons and Informal Caregivers Survey Minimum
      DataSet (TOPICS-MDS).
AB  - PURPOSE: Validity is a contextual aspect of a scale which may differ across
      sample populations and study protocols. The objective of our study was to
      validate the Care-Related Quality of Life Instrument (CarerQol) across two
      different study design features, sampling framework (general population vs.
      different care settings) and survey mode (interview vs. written questionnaire).
      METHODS: Data were extracted from The Older Persons and Informal Caregivers
      Minimum DataSet (TOPICS-MDS, www.topics-mds.eu ), a pooled public-access data set
      with information on >3,000 informal caregivers throughout the Netherlands. Meta
      correlations and linear mixed models between the CarerQol's seven dimensions
      (CarerQol-7D) and caregiver's level of happiness (CarerQol-VAS) and self-rated
      burden (SRB) were performed. RESULTS: The CarerQol-7D dimensions were correlated
      to the CarerQol-VAS and SRB in the pooled data set and the subgroups. The
      strength of correlations between CarerQol-7D dimensions and SRB was weaker among
      caregivers who were interviewed versus those who completed a written
      questionnaire. The directionality of associations between the CarerQol-VAS, SRB
      and the CarerQol-7D dimensions in the multivariate model supported the construct
      validity of the CarerQol in the pooled population. Significant interaction terms
      were observed in several dimensions of the CarerQol-7D across sampling frame and
      survey mode, suggesting meaningful differences in reporting levels. CONCLUSIONS:
      Although good scientific practice emphasises the importance of re-evaluating
      instrument properties in individual research studies, our findings support the
      validity and applicability of the CarerQol instrument in a variety of settings.
      Due to minor differential reporting, pooling CarerQol data collected using mixed
      administration modes should be interpreted with caution; for TOPICS-MDS, meta
      analytic techniques may be warranted.

PMID- 25381122
TI  - Measuring caregiver outcomes in palliative care: a construct validation study of
      two instruments for use in economic evaluations.
AB  - PURPOSE: Providing care to patients nearing the end of life can place a
      considerable burden on caregivers. Hence, policy decisions on interventions in
      palliative care should be guided by information on this burden. This study
      investigates construct validation of two preference-based caregiver outcome
      instruments suitable for economic evaluations: the Carer Experience Scale (CES)
      and the Care-related Quality of Life (CarerQol) instrument. Moreover, this study
      reports caregiver experiences in end-of-life care. METHODS: Data were collected
      with written questionnaires among caregivers of patients receiving palliative
      care services in the Southern metropolitan area of Adelaide, South Australia (n =
      97). The effect of caregiving on caregivers was measured with the CES, CarerQol,
      Process Utility (PU) and Caregiver Strain Index (CSI). Convergent, discriminative
      and clinical validity were studied. RESULTS: As hypothesized, higher negative
      effect of caregiving measured on the CES was associated with higher negative
      effect on the CarerQol. Both the CES and CarerQol were associated in the expected
      positive direction with less strain from caregiving (CSI), more positive care
      experiences and more PU from caring. Caregivers' and care recipients' health
      status and duration of caregiving were negatively associated with caring
      experiences. CONCLUSIONS: Our findings suggest that the CES and CarerQol validly
      assess the effect of caregiving on caregivers in end-of-life care. Economic
      evaluations in end-of-life care should attempt to incorporate such instruments to
      provide a more holistic assessment of the true impact of interventions,
      especially where family and friends are heavily involved in caregiving.

PMID- 25381123
TI  - Predicting participation in meaningful activity for older adults with cancer.
AB  - PURPOSE: Participation in activity that is personally meaningful leads to
      improved emotional and physical well-being and quality of life. However, little
      is known about what predicts participation in meaningful activity by older adults
      with cancer. METHODS: Seventy-one adults aged 65 years and older with a diagnosis
      of cancer were enrolled. All adults were evaluated with the following: a brief
      geriatric assessment, the meaningful activity participation assessment (MAPA),
      and the Possibilities for Activity Scale (PActS). The MAPA measures participation
      in meaningful activity, and the PActS measures what older adults believe they
      should and could be doing. A regression approach was used to assess the
      predictors of meaningful activity participation. RESULTS: The PActS (B = .56, p <
      .001) was the strongest predictor of meaningful activity participation.
      CONCLUSIONS: What older adults with cancer feel they should and could do
      significantly predicted meaningful participation in activities above and beyond
      clinical and demographic factors. In future research, perceptions of
      possibilities for activity may be useful in the design of interventions targeted
      to improve meaningful participation in older adults with cancer.

PMID- 25381124
TI  - Predictors of health-related quality of life perceived by end-stage renal disease
      patients under online hemodiafiltration.
AB  - PURPOSE: Patients' perception of health-related quality of life (HRQOL) is a
      consistent and powerful predictor of the outcome of end-stage renal disease
      (ESRD) patients under dialysis. This study aims to identify factors that could
      affect the HRQOL of ESRD patients under online hemodiafiltration (OL-HDF).
      METHODS: We evaluated 322 ESRD patients under OL-HDF (59.63% males; 64.9 +/- 14.3
      years old) from five dialysis units in the north of Portugal. Socio-demographic
      data, comorbidities, hematological data, iron status, dialysis adequacy,
      nutritional and inflammatory markers were collected from patients records.
      Patient's reported HRQOL score was assessed by using the Kidney Disease Quality
      of Life-Short Form (KDQOL-SF). RESULTS: ESRD patients showed a mean (+/- SD) of
      53.17% (+/- 15.31%) in SF-36 total score, 50.17% (+/- 9.51%) in the SF-36 mental
      component summary (MCS) and 49.75% (+/- 9.44%) in the SF-36 physical component
      summary (PCS). Red cell distribution width (RDW), feminine gender and diabetes
      were found as significant predictors of SF-36 total score of HRQOL, which
      accounts for 12% of the total explained variance. Patient satisfaction, RDW, body
      mass index and gender were identified as predictors for the PCS, which accounts
      for 22% of total explained variance. Furthermore, patient satisfaction and dry
      weight were found as predictors for MCS. These predictors accounted for 28% of
      the total explained variance. CONCLUSIONS: Our results showed that the
      coexistence of diabetes, gender and erythropoietic disturbances are predictors of
      HRQOL in patients under OL-HDF and suggest that more attention should be given to
      woman patients, to the improvement of anemia and to diabetic patients, who are
      more prone to perceive a worst HRQOL.

PMID- 25381125
TI  - A novel CD46 mutation in a patient with microangiopathy clinically resembling
      thrombotic thrombocytopenic purpura and normal ADAMTS13 activity.

PMID- 25381126
TI  - In vitro human embryonic stem cell hematopoiesis mimics MYB-independent yolk sac
      hematopoiesis.
AB  - Although hematopoietic precursor activity can be generated in vitro from human
      embryonic stem cells, there is no solid evidence for the appearance of
      multipotent, self-renewing and transplantable hematopoietic stem cells. This
      could be due to short half-life of hematopoietic stem cells in culture or,
      alternatively, human embryonic stem cell-initiated hematopoiesis may be
      hematopoietic stem cell-independent, similar to yolk sac hematopoiesis,
      generating multipotent progenitors with limited expansion capacity. Since a MYB
      was reported to be an excellent marker for hematopoietic stem cell-dependent
      hematopoiesis, we generated a MYB-eGFP reporter human embryonic stem cell line to
      study formation of hematopoietic progenitor cells in vitro. We found CD34(+)
      hemogenic endothelial cells rounding up and developing into CD43(+) hematopoietic
      cells without expression of MYB-eGFP. MYB-eGFP(+) cells appeared relatively late
      in embryoid body cultures as CD34(+)CD43(+)CD45(-/lo) cells. These MYB-eGFP(+)
      cells were CD33 positive, proliferated in IL-3 containing media and hematopoietic
      differentiation was restricted to the granulocytic lineage. In agreement with
      data obtained on murine Myb(-/-) embryonic stem cells, bright eGFP expression was
      observed in a subpopulation of cells, during directed myeloid differentiation,
      which again belonged to the granulocytic lineage. In contrast, CD14(+) macrophage
      cells were consistently eGFP(-) and were derived from eGFP-precursors only. In
      summary, no evidence was obtained for in vitro generation of MYB(+) hematopoietic
      stem cells during embryoid body cultures. The observed MYB expression appeared
      late in culture and was confined to the granulocytic lineage. 

PMID- 25381128
TI  - The prognostic value of multiparameter flow cytometry minimal residual disease
      assessment in relapsed multiple myeloma.

PMID- 25381127
TI  - The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma
      associated with hepatitis C virus infection.
AB  - Hepatitis C virus has been found to be associated with B-cell non-Hodgkin
      lymphomas, mostly marginal zone lymphomas and diffuse large B-cell lymphoma.
      Deregulation of signaling pathways involved in normal marginal zone development
      (NOTCH pathway, NF-kappaB, and BCR signaling) has been demonstrated in splenic
      marginal zone lymphoma. We studied mutations of NOTCH pathway signaling in 46
      patients with hepatitis C virus-positive diffuse large B-cell lymphoma and in 64
      patients with diffuse large B-cell lymphoma unrelated to HCV. NOTCH2 mutations
      were detected in 9 of 46 (20%) hepatitis C virus-positive patients, and NOTCH1
      mutations in 2 of 46 (4%). By contrast, only one of 64 HCV-negative patients had
      a NOTCH1 or NOTCH2 mutation. The frequency of the NOTCH pathway lesions was
      significantly higher in hepatitis C virus-positive patients (P=0.002). The 5-year
      overall survival was 27% (95%CI: 5%-56%) for hepatitis C virus-positive diffuse
      large B-cell lymphoma patients carrying a NOTCH pathway mutation versus 62%
      (95%CI: 42%-77%) for those without these genetic lesions. By univariate analysis,
      age over 60 years, NOTCH2 mutation, and any mutation of the NOTCH pathway
      (NOTCH2, NOTCH1, SPEN) were associated with shorter overall survival. Mutation of
      the NOTCH pathway retained an independent significance (P=0.029). In conclusion,
      a subset of patients with hepatitis C virus-positive diffuse large B-cell
      lymphoma displays a molecular signature of splenic marginal zone and has a worse
      clinical outcome. 

PMID- 25381129
TI  - Characterization of gene mutations and copy number changes in acute myeloid
      leukemia using a rapid target enrichment protocol.
AB  - Prognostic stratification is critical for making therapeutic decisions and
      maximizing survival of patients with acute myeloid leukemia. Advances in the
      genomics of acute myeloid leukemia have identified several recurrent gene
      mutations whose prognostic impact is being deciphered. We used HaloPlex target
      enrichment and Illumina-based next generation sequencing to study 24 recurrently
      mutated genes in 42 samples of acute myeloid leukemia with a normal karyotype.
      Read depth varied between and within genes for the same sample, but was
      predictable and highly consistent across samples. Consequently, we were able to
      detect copy number changes, such as an interstitial deletion of BCOR, three MLL
      partial tandem duplications, and a novel KRAS amplification. With regards to
      coding mutations, we identified likely oncogenic variants in 41 of 42 samples.
      NPM1 mutations were the most frequent, followed by FLT3, DNMT3A and TET2. NPM1
      and FLT3 indels were reported with good efficiency. We also showed that DNMT3A
      mutations can persist post-chemotherapy and in 2 cases studied at diagnosis and
      relapse, we were able to delineate the dynamics of tumor evolution and give
      insights into order of acquisition of variants. HaloPlex is a quick and reliable
      target enrichment method that can aid diagnosis and prognostic stratification of
      acute myeloid leukemia patients. 

PMID- 25381131
TI  - A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with
      relapsed or refractory acute myeloid leukemia.
AB  - Vosaroxin is a first-in-class anticancer quinolone derivative that intercalates
      DNA and inhibits topoisomerase II. This study assessed the safety and
      tolerability of vosaroxin plus cytarabine in patients with relapsed/refractory
      acute myeloid leukemia. Escalating vosaroxin doses (10-minute infusion; 10-90
      mg/m(2); days 1, 4) were given in combination with cytarabine on one of two
      schedules: schedule A (24-hour continuous intravenous infusion, 400 mg/m(2)/day,
      days 1-5) or schedule B (2-hour intravenous infusion, 1 g/m(2)/day, days 1-5).
      Following dose escalation, enrollment was expanded at the maximum tolerated dose.
      Of 110 patients enrolled, 108 received treatment. The maximum tolerated dose of
      vosaroxin was 80 mg/m(2) for schedule A (dose-limiting toxicities: grade 3 bowel
      obstruction and stomatitis) and was not reached for schedule B (recommended phase
      2 dose: 90 mg/m(2)). In the efficacy population (all patients in first relapse or
      with primary refractory disease treated with vosaroxin 80-90 mg/m(2); n=69), the
      complete remission rate was 25% and the complete remission/complete remission
      with incomplete blood count recovery rate was 28%. The 30-day all-cause mortality
      rate was 2.5% among all patients treated at a dose of 80-90 mg/m(2). Based upon
      these results, a phase 3 trial of vosaroxin plus cytarabine was initiated in
      patients with relapsed/refractory acute myeloid leukemia. (Clinicaltrials.gov
      identifier: NCT00541866).

PMID- 25381130
TI  - In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm
      to SL-401, an interleukin-3 receptor targeted biologic agent.
AB  - Blastic plasmacytoid dendritic cell neoplasm is an aggressive malignancy derived
      from plasmacytoid dendritic cells. There is currently no accepted standard of
      care for treating this neoplasm, and therapeutic strategies have never been
      prospectively evaluated. Since blastic plasmacytoid dendritic cell neoplasm cells
      express high levels of interleukin-3 receptor alpha chain (IL3-Ralpha or CD123),
      antitumor effects of the interleukin-3 receptor-targeted drug SL-401 against
      blastic plasmacytoid dendritic cell neoplasm were evaluated in vitro and in vivo.
      The cytotoxicity of SL-401 was assessed in patient-derived blastic plasmacytoid
      dendritic cell neoplasm cell lines (CAL-1 and GEN2.2) and in primary blastic
      plasmacytoid dendritic cell neoplasm cells isolated from 12 patients using flow
      cytometry and an in vitro cytotoxicity assay. The cytotoxic effects of SL-401
      were compared to those of several relevant cytotoxic agents. SL-401 exhibited a
      robust cytotoxicity against blastic plasmacytoid dendritic cell neoplasm cells in
      a dose-dependent manner. Additionally, the cytotoxic effects of SL-401 were
      observed at substantially lower concentrations than those achieved in clinical
      trials to date. Survival of mice inoculated with a blastic plasmacytoid dendritic
      cell neoplasm cell line and treated with a single cycle of SL-401 was
      significantly longer than that of untreated controls (median survival, 58 versus
      17 days, P<0.001). These findings indicate that blastic plasmacytoid dendritic
      cell neoplasm cells are highly sensitive to SL-401, and support further
      evaluation of SL-401 in patients suffering from blastic plasmacytoid dendritic
      cell neoplasm. 

PMID- 25381132
TI  - Pharmacological targeting of beta-catenin in normal karyotype acute myeloid
      leukemia blasts.

PMID- 25381133
TI  - A rare case of IGH/MYC and IGH/BCL2 double hit primary plasma cell leukemia.

PMID- 25381134
TI  - Prognostic influence of macrophages in patients with diffuse large B-cell
      lymphoma: a correlative study from a Nordic phase II trial.
AB  - The prognostic impact of the tumor microenvironment in diffuse large B-cell
      lymphoma has not been systematically assessed. We analyzed mRNA and antigen
      expression of monocytes, macrophages, lymphocytes, dendritic and natural killer
      cells in pretreatment tumor samples of patients with high-risk diffuse large B
      cell lymphoma using gene expression microarray and immunohistochemistry. The
      patients were treated in a Nordic phase II study with dose-dense
      chemoimmunotherapy and central nervous system prophylaxis. Of the studied markers
      for non-malignant inflammatory cells, CD68 expression and CD68(+) macrophage
      counts correlated with favorable outcome. Five-year progression-free survival
      rates were 83% and 43% for the patients with high and low CD68 mRNA levels,
      respectively (P=0.007), while overall survival rates were 83% and 64%,
      respectively (P=ns). The patients with high CD68(+) macrophage counts had better
      5-year progression-free survival (74% versus 40%; P=0.003) and overall survival
      (90% versus 60%; P=0.009) than the patients with low macrophage counts. Low
      CD68(+) macrophage count retained its prognostic impact on overall survival with
      age-adjusted International Prognostic Index [RR=5.0 (95% CI 1.024-19.088);
      P=0.017]. The findings were validated in three independent cohorts of patients
      treated with chemoimmunotherapy. In contrast, in patients treated with
      chemotherapy, high CD68(+) macrophage count was associated with poor progression
      free survival (40% versus 72%; P=0.021) and overall survival (39% versus 72%;
      P=0.015). Together, the data suggest that macrophages exhibit a dual, treatment
      specific role in diffuse large B-cell lymphoma. For the patients treated with
      chemoimmunotherapy, high pretreatment CD68 mRNA levels and CD68(+) macrophage
      numbers predict a favorable outcome. 

PMID- 25381135
TI  - Viscosupplementation of synovial fluid with xanthan gum for treatment of
      osteoarthritis and its clearance kinetics in the rabbit knee joint.
AB  - BACKGROUND: Injection of xanthan gum (XG) has been demonstrated to reduce the
      symptoms and progression of osteoarthritis (OA) in experimental models. Due to
      its high viscosity and stability, it may restore the rheological homeostasis of
      osteoarthritic synovial fluid (SF), and avoid numerous intra-articular
      injections. OBJECTIVE: The present study investigated the effect of XG on the
      rheological properties of SF, and determined its residence time in the rabbit
      joint cavity. METHODS: Rabbit knees were subject to intra-articular injection
      with XG or XG labeled with green fluorescence, and the SF was collected at
      different time. Rheological properties of SF with XG injected were compared with
      those with sodium hyaluronate injected. Resistance to oxidant damage was tested
      by adding H2O2 to the viscosupplement. Fluorescence intensity was measured for
      the SF with XG labeled with green fluorescence. RESULTS: Results showed that XG
      could significantly improve the SF viscosity at 24, 96, 168 h, and increase the
      storage moduli (G') and loss moduli (G") tested at frequency of 0.5 and 2.5 Hz.
      SF with XG injection exhibited a gel-like behavior at 24 h, in that G' exceed G"
      over the entire oscillation frequency range. XG preparation had a high resistance
      to oxidant damage. Half-life of XG in the joint cavity was 35.9 h, with clearance
      obeying first-order kinetics. CONCLUSIONS: Intra-articular injection of XG could
      improve the rheological properties of SF, and this effect could last for several
      days.

PMID- 25381137
TI  - Phylogeny and biogeography of the invasive cyanobacterium Cylindrospermopsis
      raciborskii.
AB  - Cylindrospermopsis raciborskii is a toxic cyanobacterium with an invasive nature.
      The species is found in all the main continents but its origin and dispersal
      routes on a worldwide perspective remain yet mostly unknown. In this study, 27
      isolates of C. raciborskii gathered worldwide have been used for an in-deep
      phylogenetic analyses with a concatenated system of three genetic markers (16
      rRNA, 16S-23S ITS larger subunit, and RNA polymerase rpoC1) comprehending 3,188
      bp. Our results provide support for an origin of C. raciborskii in the American
      continent. Dispersal routes included afterward a spread into the African
      continent and then Asia and Australia, being Europe the last continent to be
      colonized by this species. Our phylogenetic inferences suggest that C.
      raciborskii seem to have a well-defined dispersal behavior with a well
      established population structure around the world. 

PMID- 25381136
TI  - Efficacy of eribulin in women with metastatic breast cancer: a pooled analysis of
      two phase 3 studies.
AB  - Data from two phase 3 studies of eribulin were pooled in analyses initially
      requested by the European Medicines Agency to assess whether specific patient
      subgroups, previously treated with an anthracycline and a taxane, benefited from
      eribulin. Study 305/EMBRACE included women after two-to-five lines of
      chemotherapy for advanced breast cancer who were randomized to eribulin mesylate
      (1.4 mg/m(2) on days 1 and 8 every 21 days) or treatment of physician's choice.
      In Study 301, patients who had received up to two prior chemotherapy regimens for
      advanced disease were randomized to eribulin (as above) or capecitabine (1.25
      g/m(2) b.i.d. on days 1-14 every 21 days). In the pooled population, overall
      survival (OS), progression-free survival and response rates were analysed in the
      intent-to-treat population and selected subgroups. Overall, 1,062 patients were
      randomized to eribulin and 802 patients to control. Median OS was 15.2 months
      with eribulin versus 12.8 months with control (hazard ratio [HR] 0.85; 95% CI
      0.77, 0.95; P = 0.003). In all subgroups assessed, OS data favoured eribulin;
      significant improvements occurred in some subgroups, notably in women with human
      epidermal growth factor receptor 2 (HER2)-negative disease (HR 0.82; P = 0.002),
      although the effect in those with HER2-negative but hormone-receptor-positive
      disease did not reach statistical significance; benefits were also seen, among
      others, in those with estrogen-receptor-negative and triple-negative disease.
      Eribulin improves OS in various patient subgroups with advanced/metastatic breast
      cancer who had previously received an anthracycline and a taxane. Women with HER2
      negative disease are among those who may obtain benefit from eribulin.

PMID- 25381138
TI  - Halorussus ruber sp. nov., isolated from an inland salt lake of China.
AB  - Halophilic archaeal strain YC25(T) was isolated from Yuncheng salt lake in
      Shanxi, China. Cells of strain YC25(T) were observed to be pleomorphic rods,
      stained Gram-negative, and formed red-pigmented colonies on solid media. Strain
      YC25(T) was found to be able to grow at 25-50  degrees C (optimum 37  degrees C),
      at 1.4-4.8 M NaCl (optimum 1.7 M), at 0-1.0 M MgCl2 (optimum 0.01 M), and at pH
      5.5-9.0 (optimum pH 6.5). The cells lysed in distilled water, and the minimal
      NaCl concentration to prevent cell lysis was found to be 8 % (w/v). The major
      polar lipids of the strain were phosphatidylglycerol (PG), phosphatidylglycerol
      phosphate methyl ester (PGP-Me), phosphatidylglycerol sulfate (PGS), sulfated
      galactosyl mannosyl glucosyl diether (S-TGD-1), sulfated mannosyl glucosyl
      diether (S-DGD-1), galactosyl mannosyl glucosyl diether (TGD-1), mannosyl
      glucosyl diether (DGD-1), and an unknown diglycosyl diether (DGD-2)
      chromatographically identical to those of Halorussus rarus CGMCC 1.10122(T). The
      16S rRNA gene and rpoB' gene of strain YC25(T) were phylogenetically related to
      the corresponding genes of Halorussus rarus CGMCC 1.10122(T) (94.3-95.4 and 91.5
      % nucleotide identity, respectively). The DNA G+C content of strain YC25(T) was
      determined to be 63.3 mol%. The phenotypic, chemotaxonomic, and phylogenetic
      properties suggested that strain YC25(T) (=CGMCC 1.12122(T) = JCM 18363(T))
      represents a new species of Halorussus, for which the name Halorussus ruber sp.
      nov. is proposed. 

PMID- 25381139
TI  - Spot testing by GPs for bacterial infections reduces antibiotic use, study finds.

PMID- 25381140
TI  - Nation wide epidemiological survey of primary palmar hyperhidrosis in the
      People's Republic of China.
AB  - OBJECTIVE: To investigate the prevalence and epidemiological characteristics of
      primary palmar hyperhidrosis (PPH) among adolescents in PR China. METHODS: A
      nationwide survey was performed, including all seven geological areas of Mainland
      China. Stratified cluster sampling was performed, and a cross-sectional
      epidemiological survey was applied via questionnaire among 10,000 college
      students in each geological area. RESULTS: The prevalence rate of PPH was 2.08%.
      The prevalence in female adolescents was slightly higher than the prevalence in
      male adolescents (2.29 vs. 1.94%). The prevalence of PPH in coastal areas was
      higher than the prevalence of PPH in inland areas (2.81 vs. 1.53%). The peak age
      of onset is 7-15 years, accounting for 97.3% of the PPH population. Positive
      family history was found in 25.40% of PPH cases. In addition to palms, axillae
      and soles can also be affected. CONCLUSIONS: PPH affects a larger group of
      individuals than previously reported. More measures should be taken to enhance
      the recognition, diagnosis, and treatment of PPH.

PMID- 25381141
TI  - Histone deacetylase inhibitors for enhancing activity of antifungal agent: a
      patent evaluation of WO2014041424(A1).
AB  - Novel histone deacetylase inhibitors have been developed for the antifungal
      therapy. Molecule 8 exhibited potent antifungal activities with MIC values of
      0.25/0.25, 0.12/0.25, 0.12/0.12 ug/ml against Candida albicans, C. parapsilosis
      and C. glabrata after 24/48 h incubation, respectively. Most of the synthesized
      compound showed significantly synergistic effects with fluconazole in the
      biological assay. The discovery of these molecules makes positive contributions
      to the development of potent and safe antifungal drugs. 

PMID- 25381142
TI  - Nonalcoholic Fatty Liver Disease, Cardiovascular Risk, and Carotid Inflammation.

PMID- 25381143
TI  - Confounding factors may affect mean platelet volume in chronic urticaria.

PMID- 25381145
TI  - Online social networking in people with psychosis: A systematic review.
AB  - BACKGROUND: Online social networking might facilitate the establishment of social
      contacts for people with psychosis, who are often socially isolated by the
      symptoms and consequences of their disorder. AIMS: We carried out a systematic
      review exploring available evidence on the use of online social networking in
      people with psychosis. METHODS: The review was conducted following Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      Included studies examined the use of the online social networking by people with
      an a priori diagnosis of psychosis (inclusive of bipolar disorder). Data from
      included studies were extracted and narratively synthesised. RESULTS: A total of
      11 studies, published between 2005 and 2013, reported data on online social
      networking in people with psychosis. People with psychosis seem to spend more
      time in chat rooms or playing online games than control groups. The use of other
      online tools, such as Facebook or communication through e-mail, is lower or the
      same than controls. Online social networking was used by patients with psychosis
      for establishing new relationships, maintaining relationships/reconnecting with
      people and online peer support. CONCLUSION: Online social networking, in the form
      of forums or online chats, could play a role in strategies aimed at enhancing
      social networks and reduce the risk of isolation in this population.

PMID- 25381144
TI  - Acute Coronary Syndrome in Indian Subcontinent Patients Residing in the Middle
      East: Results From Gulf Registry of Acute Coronary Events II.
AB  - We compared baseline characteristics, clinical presentation, and in-hospital
      outcomes between Middle Eastern Arabs and Indian subcontinent patients presenting
      with acute coronary syndrome (ACS). Of the 7930 patients enrolled in Gulf
      Registry of Acute Coronary Events II (RACE II), 23% (n = 1669) were from the
      Indian subcontinent. The Indian subcontinent patients, in comparison with the
      Middle Eastern Arabs, were younger (49 vs 60 years; P < .001), more were males
      (96% vs 80%; P < .001), had lower proportion of higher Global Registry of Acute
      Coronary Events risk score (8% vs 27%; P < .001), and less likely to be
      associated with diabetes (34% vs 42%; P < .001), hypertension (36% vs 51%; P <
      .001), and hyperlipidemia (29% vs 39%; P < .001) but more likely to be smokers
      (55% vs 29%; P < .001). After multivariable adjustment, the Middle Eastern Arabs
      were less likely to be associated with in-hospital congestive heart failure (odds
      ratio [OR], 0.65; 95% confidence interval [CI]: 0.50-0.86; P = .003) but more
      likely to be associated with recurrent ischemia (OR 1.33; 95% CI: 1.03-1.71; P =
      .026) when compared to the Indian subcontinent patients. Despite the baseline
      differences, there were largely no significant differences in in-hospital
      outcomes between the Indians and the Middle Eastern Arabs.

PMID- 25381146
TI  - Impact of migration on fertility and abortion: evidence from the household and
      welfare study of Accra.
AB  - Over the last few decades, total fertility rates, child morbidity, and child
      mortality rates have declined in most parts of sub-Saharan Africa. Among the most
      striking trends observed are the rapid rate of urbanization and the often
      remarkably large gaps in fertility between rural and urban areas. Although a
      large literature has highlighted the importance of migration and urbanization
      within countries' demographic transitions, relatively little is known regarding
      the impact of migration on migrants' reproductive health outcomes in general and
      abortion in particular. In this article, we use detailed pregnancy and migration
      histories collected as part of the Household and Welfare Study of Accra (HAWS) to
      examine the association between migration and pregnancy outcomes among women
      residing in the urban slums of Accra, Ghana. We find that the completed fertility
      patterns of lifetime Accra residents are remarkably similar to those of residents
      who migrated. Our results suggest that recent migrants have an increased risk of
      pregnancy but not an increased risk of live birth in the first years post-move
      compared with those who had never moved. This gap seems to be largely explained
      by an increased risk of miscarriage or abortion among recent migrants. Increasing
      access to contraceptives for recent migrants has the potential to reduce the
      incidence of unwanted pregnancies, lower the prevalence of unsafe abortion, and
      contribute to improved maternal health outcomes. 

PMID- 25381147
TI  - Staphylococcal enterotoxin B administration during pregnancy imprints the
      increased CD4:CD8 T-cell ratio in the peripheral blood from neonatal to adult
      offspring rats.
AB  - Our previous study demonstrated that Staphylococcal enterotoxin B (SEB)
      administration during pregnancy could alter the percentage of T cells
      subpopulation in the thymus of the neonatal rats; however, little is known about
      the effect of maternal SEB administration during pregnancy on T cells
      subpopulation in the peripheral blood of the offspring rats. In the present
      study, pregnant rats at gestational day 16 were intravenously injected with 15 ug
      SEB. The present study found that prenatal exposure to SEB significantly
      decreased the percentages of CD8 T cells in the peripheral blood of both neonatal
      rats on the fifth day after delivery and the adult offspring rats. Furthermore,
      it significantly increased the percentage of CD4 T cells as well as the ratios of
      CD4 to CD8 T cells in both neonatal and adult offspring rats. Prenatal exposure
      to SEB significantly decreased the expression levels of IL-4 and IFN-gamma in the
      plasma of neonatal and adult offspring rats. Furthermore, SEB restimulation
      significantly increased the percentage of CD8 T cells and significantly decreased
      the percentage of CD4 T cells. These data suggest the prenatal exposure to SEB
      can imprint the increased CD4:CD8 T cell ratio in the peripheral blood from the
      neonate to adulthood through the decreased CD8 T cells and the increased CD4 T
      cells, and altered the response characteristics of CD4 and CD8 T cells to
      secondary SEB administration in the peripheral blood of the adult offspring rats.

PMID- 25381148
TI  - Molecular characterization of carbapenemase and cephalosporinase genes among
      clinical isolates of Acinetobacter baumannii in a tertiary medical centre in
      Malaysia.
AB  - Antimicrobial resistance in Acinetobacter baumannii is a growing public health
      concern and an important pathogen in nosocomial infections. We investigated the
      genes involved in resistance to carbapenems and cephalosporins in clinical A.
      baumannii isolates from a tertiary medical centre in Malaysia. A. baumannii was
      isolated from 167 clinical specimens and identified by sequencing of the 16S rRNA
      and rpoB genes. The MIC for imipenem, meropenem, ceftazidime and cefepime were
      determined by the E-test method. The presence of carbapenemase and
      cephalosporinase genes was investigated by PCR. The isolates were predominantly
      nonsusceptible to carbapenems and cephalosporins (>70 %) with high MIC values.
      ISAba1 was detected in all carbapenem-nonsusceptible A. baumannii harbouring the
      blaOXA-23-like gene. The presence of blaOXA-51-like and ISAba1 upstream of blaOXA
      51 was not associated with nonsusceptibility to carbapenems. A. baumannii
      isolates harbouring ISAba1-blaADC (85.8 %) were significantly associated with
      nonsusceptibility to cephalosporins (P<0.0001). However, ISAba1-blaADC was not
      detected in a minority (<10 %) of the isolates which were nonsusceptible to
      cephalosporins. The acquired OXA-23 enzymes were responsible for
      nonsusceptibility to carbapenems in our clinical A. baumannii isolates and
      warrant continuous surveillance to prevent further dissemination of this
      antibiotic resistance gene. The presence of ISAba1 upstream of the blaADC was a
      determinant for cephalosporin resistance. However, the absence of this ISAba1
      blaADC in some of the isolates may suggest other resistance mechanisms and need
      further investigation. 

PMID- 25381149
TI  - Discourse on medicine: meditative and calculative approaches to ethics from an
      international perspective.
AB  - Heidegger's two modes of thinking, calculative and meditative, were used as the
      thematic basis for this qualitative study of physicians from seven countries
      (Canada, China, India, Ireland, Japan, Korea, & Thailand). Focus groups were
      conducted in each country with 69 physicians who cared for the elderly. Results
      suggest that physicians perceived ethical issues primarily through the lens of
      calculative thinking (76%) with emphasis on economic concerns. Meditative
      responses represented 24% of the statements and were mostly generated by Canadian
      physicians whose patients typically were not faced with economic barriers to
      treatment due to Canada's universal health care system. 

PMID- 25381151
TI  - The Involvement of Morphological Information in the Memorization of Chinese
      Compound Words: Evidence from Memory Errors.
AB  - The processing of morphological information during Chinese word memorization was
      investigated in the present study. Participants were asked to study words
      presented to them on a computer screen in the studying phase and then judge
      whether presented words were old or new in the test phase. In addition to parent
      words (i.e. the words studied in the study phase), the test phase also included
      conjunction lures (constructed out of morphemes in the parent words) and new
      words (constructed out of entirely new morphemes). Three kinds of words (i.e.
      subordinate compounds, coordinative compounds, and single-morpheme words) were
      involved. In both two experiments, performance on lures worsened when both parent
      words and lures were coordinative compounds, compared to the condition when both
      were subordinate compounds. The different performance between compounds with
      different compounding structures in the test phase suggests the involvement of
      morphological information in the memorization of Chinese compound words. The
      spreading activation theory for memory and the interactive activation model for
      the processing of morphologically complex words were referred to for interpreting
      the results. 

PMID- 25381150
TI  - Cystic renal cell carcinoma: a report of 67 cases including 4 cases with
      concurrent renal cell carcinoma.
AB  - BACKGROUND: Cystic renal cell carcinoma (CRCC) is relatively rare; CRCC is
      frequently misdiagnosed as a benign renal cyst. CRCC carries an excellent
      prognosis following surgical treatment. The aim of our study was to summarize the
      management of CRCC and to characterize the prognosis of affected patients.
      METHODS: A retrospective study of 67 patients with CRCC was conducted at our
      center between January 2005 and April 2013. Patient prognosis as well as the
      clinical manifestations, imaging characteristics, treatment, and pathologic
      features of CRCC were summarized based on available medical record data. RESULTS:
      We identified 67 cases of CRCC, representing 2.5% of all renal cell carcinoma
      cases. The tumor was discovered incidentally in 70% of the cases. Ultrasonography
      was found to be a useful screening tool, but computed tomography remains the
      imaging study of choice for identifying malignant features. Magnetic resonance
      imaging can be used in equivocal cases. Regarding treatment, radical nephrectomy
      was performed in 52% of the cases, and partial nephrectomy was selected in the
      remaining 48% of cases. None of the 46 patients (68% of the study group)
      available for follow-up showed any evidence of recurrence. CONCLUSIONS: CRCC is
      an uncommon subtype of renal cell carcinoma, occurring in 2.5% of cases. CRCC
      carries an excellent prognosis after surgical treatment. Partial nephrectomy
      should be regarded as the preferred surgical technique for CRCC.

PMID- 25381152
TI  - B-Raf inhibitors induce epithelial differentiation in BRAF-mutant colorectal
      cancer cells.
AB  - BRAF mutations are associated with aggressive, less-differentiated and therapy
      resistant colorectal carcinoma. However, the underlying mechanisms for these
      correlations remain unknown. To understand how oncogenic B-Raf contributes to
      carcinogenesis, in particular to aspects other than cellular proliferation and
      survival, we generated three isogenic human colorectal carcinoma cell line models
      in which we can dynamically modulate the expression of the B-Raf(V600E)
      oncoprotein. Doxycyclin-inducible knockdown of endogenous B-Raf(V600E) decreases
      cellular motility and invasion in conventional and three-dimensional (3D)
      culture, whereas it promotes cell-cell contacts and induces various hallmarks of
      differentiated epithelia. Importantly, all these effects are recapitulated by B
      Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib).
      Surprisingly, loss of B-Raf(V600E) in HT29 xenografts does not only stall tumor
      growth, but also induces glandular structures with marked expression of CDX2, a
      tumor-suppressor and master transcription factor of intestinal differentiation.
      By performing the first transcriptome profiles of PLX4720-treated 3D cultures of
      HT29 and Colo-205 cells, we identify several upregulated genes linked to
      epithelial differentiation and effector functions, such as claudin-1, a Cdx-2
      target gene encoding a critical tight junction component. Thereby, we provide a
      mechanism for the clinically observed correlation between mutant BRAF and the
      loss of Cdx-2 and claudin-1. PLX4720 also suppressed several metastasis
      associated transcripts that have not been implicated as targets, effectors or
      potential biomarkers of oncogenic B-Raf signaling so far. Together, we identify a
      novel facet of clinically applied B-Raf or MEK inhibitors by showing that they
      promote cellular adhesion and differentiation of colorectal carcinoma cells.

PMID- 25381153
TI  - VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells.
AB  - Anti-VEGF therapy perturbs tumor metabolism, severely impairing oxygen, glucose,
      and ATP levels. In this study, we investigated the effects of anti-VEGF therapy
      in multiple experimental tumor models that differ in their glycolytic phenotypes
      to gain insights into optimal modulation of the metabolic features of this
      therapy. Prolonged treatments induced vascular regression and necrosis in tumor
      xenograft models, with highly glycolytic tumors becoming treatment resistant more
      rapidly than poorly glycolytic tumors. By PET imaging, prolonged treatments
      yielded an increase in both hypoxic and proliferative regions of tumors. A
      selection for highly glycolytic cells was noted and this metabolic shift was
      stable and associated with increased tumor aggressiveness and resistance to VEGF
      blockade in serially transplanted mice. Our results support the hypothesis that
      the highly glycolytic phenotype of tumor cells studied in xenograft models,
      either primary or secondary, is a cell-autonomous trait conferring resistance to
      VEGF blockade. The finding that metabolic traits of tumors can be selected by
      antiangiogenic therapy suggests insights into the evolutionary dynamics of tumor
      metabolism.

PMID- 25381154
TI  - The cyclic AMP pathway is a sex-specific modifier of glioma risk in type I
      neurofibromatosis patients.
AB  - Identifying modifiers of glioma risk in patients with type I neurofibromatosis
      (NF1) could help support personalized tumor surveillance, advance understanding
      of gliomagenesis, and potentially identify novel therapeutic targets. Here, we
      report genetic polymorphisms in the human adenylate cyclase gene adenylate
      cyclase 8 (ADCY8) that correlate with glioma risk in NF1 in a sex-specific
      manner, elevating risk in females while reducing risk in males. This finding
      extends earlier evidence of a role for cAMP in gliomagenesis based on results in
      a genetically engineered mouse model (Nf1 GEM). Thus, sexually dimorphic cAMP
      signaling might render males and females differentially sensitive to variation in
      cAMP levels. Using male and female Nf1 GEM, we found significant sex differences
      exist in cAMP regulation and in the growth-promoting effects of cAMP suppression.
      Overall, our results establish a sex-specific role for cAMP regulation in human
      gliomagenesis, specifically identifying ADCY8 as a modifier of glioma risk in
      NF1.

PMID- 25381155
TI  - Impacts of environmental stress on growth, secondary metabolite biosynthetic gene
      clusters and metabolite production of xerotolerant/xerophilic fungi.
AB  - This paper examines the impact that single and interacting environmental stress
      factors have on tolerance mechanisms, molecular ecology and the relationship with
      secondary metabolite production by a group of mycotoxigenic species of economic
      importance. Growth of these fungi (Aspergillus flavus, A.ochraceus,
      A.carbonarius, Penicillium nordicum and P. verrucosum) is influenced by water and
      temperature interactions and type of solute used to induce water stress. Such
      abiotic stresses are overcome by the synthesis of increased amounts of low
      molecular weight sugar alcohols, especially glycerol and erythritol, to enable
      them to remain active under abiotic stress. This is accompanied by increased
      expression of sugar transporter genes, e.g., in A. flavus, which provides the
      nutritional means of tolerating such stress. The optimum conditions of water
      activity (a w) * temperature stress for growth are often different from those for
      secondary metabolite production. The genes for toxin production are clustered
      together and their relative expression is influenced by abiotic interacting
      stress factors. For example., A. flavus synthesises aflatoxins under water stress
      in non-ionic solutes. In contrast, P. nordicum specifically occupies a high salt
      (0.87 a w = 22% NaCl) niche such as cured meats, and produces ochratoxin A (OTA).
      There is differential and temporal expression of the genes in the secondary
      metabolite clusters in response to a w * temperature stress. We have used a
      microarray and integrated data on growth, relative expression of key genes in the
      biosynthetic pathways for secondary metabolite production and toxin production
      using a mixed growth model. This was used to correlate these factors and predict
      the toxin levels produced under different abiotic stress conditions. This system
      approach to integrate these different data sets and model the relationships could
      be a powerful tool for predicting the relative toxin production under extreme
      stress conditions, including climate change scenarios. This approach will
      facilitate a better functional understanding of the influence that environmental
      stress has on these mycotoxigenic fungi and enable better prevention strategies
      to be developed based on this system-based approach.

PMID- 25381156
TI  - Rock black fungi: excellence in the extremes, from the Antarctic to space.
AB  - This work focuses on rock-inhabiting fungi (RIF) of Antarctic rocky deserts,
      considered the closest to a possible Martian habitat, as the best example of
      adaptation to the extremes. The study of RIF ecophysiology, resistance and
      adaptation provides tools that shed light on the evolution of extremophily. These
      studies also help define the actual limits for life and provide insight for
      investigating its existence beyond our planet. The scientific results obtained
      from over 20 years of research on the biodiversity, phylogeny and evolution
      toward extremotolerance reviewed here demonstrate how these fascinating organisms
      can withstand conditions well beyond those in their natural environment. A final
      focus is given on results and perspectives arising from a recent proteomic
      approach, and from astrobiological experiments and their significance for future
      space exploration. These studies demonstrate that Antarctic RIF offer an
      excellent opportunity to investigate many basic, but also applicative areas of
      research on extremophily. 

PMID- 25381157
TI  - Increased Epicardial Adipose Tissue Thickness is Associated With Angiographic
      Thrombus Burden in the Patients With Non-ST-Segment Elevation Myocardial
      Infarction.
AB  - We aimed to evaluate the relation among epicardial adipose tissue (EAT)
      thickness, angiographic presence of thrombus, and the no-reflow in the patients
      with non-ST-segment elevation myocardial infarction undergoing primary
      percutaneous coronary intervention. The study population consisted of 229
      patients. The EAT thickness and neutrophil to lymphocyte ratio (NLR) were
      significantly higher in the patients with coronary thrombus than in those without
      coronary thrombus (6.1 +/- 1.1 vs 5.1 +/- 1.3 mm, P < .001 and 3.4 +/- 0.9 vs 2.5
      +/- 0.7, P < .001, respectively) and in the patients with no-reflow compared to
      patients with reflow. The EAT thickness was found to be correlated positively
      with the degree of the thrombus burden, NLR, and waist circumference and
      negatively with high-density lipoprotein cholesterol. Multivariate logistic
      regression analysis demonstrated that EAT thickness and NLR independently
      predicted coronary thrombus formation and no-reflow. We have suggested that EAT
      can play an important role in the pathophysiology of coronary thrombus formation
      and the no-reflow.

PMID- 25381159
TI  - Osteotomies of the spine: "technique of the decade"?

PMID- 25381158
TI  - Quality of life outcomes in surgically treated adult scoliosis patients: a
      systematic review.
AB  - PURPOSE: The aim of this systematic review was to identify prospective studies
      reporting the impact of surgical intervention on health-related quality of life
      (HRQL) outcomes for adults with scoliosis at a minimum 2 year follow-up. METHOD:
      An electronic database search was conducted for January 2000-November 2013 in
      conjunction with a reference list search of two related systematic reviews for
      prospective studies of adults with scoliosis reporting HRQL outcome measure.
      Methodological quality of included articles was assessed using the Downs and
      Black checklist. Cohen's d effect size was calculated for Scoliosis Research
      Society Questionnaire (SRS) and Oswestry Disability Index (ODI) outcomes for
      included studies and pooled data. RESULTS: The database and reference list
      searches returned 349 potential articles; three articles met the inclusion
      criteria. Downs and Black scores ranged from 18/28 to 21/28 (fair-good quality
      evidence). Total number of 188 patients were treated surgically and had a mean
      age of 38 years or older. All studies showed significant improvement in reported
      HRQL outcomes for at least a 2 year follow-up. The Cohen's d effect size for SRS
      was d = 1.4 (n = 188, 95 % CI; 0.9, 1.8) and for ODI d = 0.9 (n = 120, 95 % CI;
      0.4, 1.4). CONCLUSION: Findings from this review suggest surgery improves HRQL in
      patients with adult scoliosis at a minimum 2 year follow-up. However, these
      findings are based on limited data of fair to good quality which needs to be
      taken into consideration when interpreting the results and highlights the need
      for additional high quality prospective studies.

PMID- 25381160
TI  - Assessment of feto-maternal hemorrhage among rhesus D negative pregnant mothers
      using the kleihauer-betke test (KBT) and flow cytometry (FCM) in Addis Ababa,
      Ethiopia.
AB  - BACKGROUND: This study aimed to assess fetomaternal hemorrhage (FMH) among RhD
      negative pregnant mothers using two techniques, Kleihauer-Betke (KBT) and Flow
      cytometry (FCM). To determine if patient-specific doses of prophylactic anti-D
      warrant further investigation in Ethiopia and wider Africa. METHODS: Hospital-
      based cross-sectional study was conducted among 75 RhD negative pregnant mothers
      using convenient sampling technique. RESULT: FMH has been detected in 52% and 60%
      by KBT and FCM techniques, respectively. The volume of FMH quantified in the
      majority of the cases (92.5% and 87%) was <10 mL fetal blood while >30 mL in 1.3%
      (1/75) and 2.7% (2/75) as calculated by KBT and FCM, respectively. The FMH
      calculated by the two methods have good correlation; r = 0.828 (p = 0.000) for
      categorized and r = 0.897 (p = 0.000) for continuous values and the agreement
      between the FCM and KBT was moderate with kappa (kappa) value of 0.53 (p =
      0.000). CONCLUSION: Most of FMH calculated (<10 mL) could have been neutralized
      by lower doses which might have lower costs than administering 300 MUg dose which
      is currently in practice in our country for affording mothers. Besides, it also
      showed that the volume of FMH was >30 mL in 1.3% and 2.7% of the cases as
      calculated by KBT and FCM, respectively, which need more than 300 MUg dose RhIG
      for neutralization. Further investigation into the cost- effectiveness and
      scalability of patient- specific dosing of prophylactic anti-D appears warranted.

PMID- 25381161
TI  - One-year clinical outcome after laser treatment for retinopathy of prematurity at
      a tertiary center in Turkey.
AB  - The purpose of the study is to evaluate the clinical outcome of laser
      photocoagulation (LPC) in the treatment of retinopathy of prematurity (ROP) at a
      referral hospital in Turkey. In this retrospective study, a chart review of
      infants who underwent LPC for ROP between June 2011 and June 2013 was done.
      Clinical and demographic characteristics, laser parameters, anatomic, and
      refractive outcomes were evaluated. Totally 113 infants (202 eyes) were enrolled
      in the study. Of the 202 eyes, 29 eyes had threshold ROP, 141 eyes had
      prethreshold ROP, and 32 eyes had aggressive posterior ROP (APROP) at initial
      interventions. The mean gestational age (GA) was 28.13 +/- 1.99 weeks (range
      between 24 and 33 weeks), the mean birth weight (BW) was 1,147.77 +/- 341.77 g
      (range between 530 and 2,000 g) and the mean postmenstrual age (PMA) at first
      laser treatment time was 35.79 +/- 1.74 weeks (range between 33 and 39 weeks).
      The mean number of laser spots (NLS) applied for each eye was 1,358.05 +/-
      369.91. Eyes with APROP had higher number of NLS than eyes with threshold ROP and
      prethreshold ROP (P < 0.01). Anatomic outcome was favorable for 171 eyes (84.7 %)
      at the end of the 1-year follow-up. Refractive data were available for 56 infants
      (100 eyes). The mean refractive error was 0.00 +/- 2.48D SE. The incidence of
      high myopia (>5D) and strabismus was 2 and 14.3 %, respectively. Laser
      photocoagulation is an effective therapy for ROP. Early and appropriate laser
      treatment improves the clinical outcome of the disease.

PMID- 25381163
TI  - Multiple and concurrent sexual partnerships among men who have sex with men in
      Viet Nam: results from a National Internet-based Cross-sectional Survey.
AB  - Men who have sex with men (MSM) are one of the largest HIV risk groups in Viet
      Nam and have been understudied. Sexual concurrency and multiple sex partnerships
      may contribute to high HIV incidence among MSM in Viet Nam. Limited information
      is available on concurrency and multiple sexual partnerships among MSM in Viet
      Nam or on the extent to which this population engages in concurrent and multiple
      unprotected anal intercourse. Data are from a self-administered Internet-based
      survey of Vietnamese MSM aged 18 years or older, having sex with male partner(s)
      in the last 12 months and recruited from social networking MSM-specific websites
      in Viet Nam. Multiple partnerships and concurrency were measured using the UNAIDS
      recommended sexual partner matrix, a key component in the questionnaire.
      Concurrent and multiple sexual partnerships were analyzed at the individual
      level. Logistic regression analyses were conducted to assess the demographic
      characteristics and behaviors associated with multiple sexual partnerships. A
      total of 1695 MSM reported on multiple sexual partnerships; 69.5% indicated
      multiple sexual partnerships in the last 6 months. A total of 257 MSM reported on
      concurrent sexual partnerships, with 51.0% reporting penetrative sex with
      concurrent partners in the last 6 months. Respondents were more likely to engage
      in multiple sexual partnerships if they were no longer a student, consumed
      alcohol before and/or during sex, used the Internet to meet casual sex partners
      and had never participated in a behavioral HIV intervention. Multiple sexual
      partnerships in the previous 6 months were common among MSM surveyed, as was
      sexual concurrency. High levels of multiple and concurrent sexual partnerships
      may be catalyzing the transmission of HIV among MSM in Viet Nam. Given the high
      prevalence of this high-risk sexual behavior, our findings underscore the urgent
      need for targeted prevention efforts, focusing on the reduction of multiple and
      concurrent sexual partners among this key population. 

PMID- 25381162
TI  - Sex hormonal regulation and hormesis in aging and longevity: role of vitagenes.
AB  - Aging process is accompanied by hormonal changes characterized by an imbalance
      between catabolic hormones, such as cortisol and thyroid hormones which remain
      stable and hormones with anabolic effects (testosterone, insulin like growth
      factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with
      age. Deficiencies in multiple anabolic hormones have been shown to predict health
      status and longevity in older persons.Unlike female menopause, which is
      accompanied by an abrupt and permanent cessation of ovarian function (both
      folliculogenesis and estradiol production), male aging does not result in either
      cessation of testosterone production nor infertility. Although the circulating
      serum testosterone concentration does decline with aging, in most men this
      decrease is small, resulting in levels that are generally within the normal
      range. Hormone therapy (HT) trials have caused both apprehension and confusion
      about the overall risks and benefits associated with HT treatment. Stress
      response hormesis from a molecular genetic perspective corresponds to the
      induction by stressors of an adaptive, defensive response, particularly through
      alteration of gene expression. Increased longevity can be associated with greater
      resistance to a range of stressors. During aging, a gradual decline in potency of
      the heat shock response occur and this may prevent repair of protein damage.
      Conversely, thermal stress or pharmacological agents capable of inducing stress
      responses, by promoting increased expression of heat-shock proteins, confer
      protection against denaturation of proteins and restoration of proteome function.
      If induction of stress resistance increases life span and hormesis induces stress
      resistance, hormesis most likely result in increased life span. Hormesis
      describes an adaptive response to continuous cellular stresses, representing a
      phenomenon where exposure to a mild stressor confers resistance to subsequent,
      otherwise harmful, conditions of increased stress. This biphasic dose-response
      relationship, displaying low-dose stimulation and a high-dose inhibition, as
      adaptive response to detrimental lifestyle factors determines the extent of
      protection from progression to metabolic diseases such as diabetes and more in
      general to hormonal dysregulation and age-related pathologies. Integrated
      responses exist to detect and control diverse forms of stress. This is
      accomplished by a complex network of the so-called longevity assurance processes,
      which are composed of several genes termed vitagenes. Vitagenes encode for heat
      shock proteins (Hsps), thioredoxin and sirtuin protein systems. Nutritional
      antioxidants, have recently been demonstrated to be neuroprotective through the
      activation of hormetic pathways under control of Vitagene protein network. Here
      we focus on possible signaling mechanisms involved in the activation of vitagenes
      resulting in enhanced defense against functional defects leading to degeneration
      and cell death with consequent impact on longevity processes. 

PMID- 25381164
TI  - Ischemic stroke associated with immune thrombocytopenia.
AB  - The objective of this study was to review all cases in literature in which the
      clinical manifestations of ischemic stroke and immune thrombocytopenia (ITP) were
      presented in the same patient including a new case of our own and discuss the
      possible mechanism and management of this syndrome. We reviewed 12 reports in
      which 18 cases were diagnosed as ischemic stroke and ITP. The clinical
      manifestations and ischemic lesion patterns of the 18 cases and our new case were
      analyzed in detail to elucidate the characteristics and management of this kind
      of syndrome. Of all the cases, 8 females and 10 males, 10 of them were Koreans; 3
      were Americans; 3 were Japanese; 1 was British and 1 was Australian. The age of
      eight patients was no more than 50 years old. Most of them had a low platelet
      count. CT and/or MRI of brain were seen in all tested cases. Prognosis of
      ischemic stroke was good in 18 of the 19 patients. Although extremely rare,
      ischemic stroke and ITP may present in the same patient with variant
      characteristics. This paradoxical mechanism and management of ischemic stroke
      associated with ITP requires further investigation.

PMID- 25381165
TI  - UK doctors could save L2bn a year by cutting waste, says report.

PMID- 25381166
TI  - Body fat distribution and associations with metabolic and clinical
      characteristics in bipolar individuals.
AB  - Overweight and obesity differentially affect bipolar disorder (BD) and are
      associated with a poorer prognosis. Herein, we sought to evaluate body fat
      distribution in a well-characterized BD sample. Anthropometric measures (i.e.,
      body mass index, waist-to-hip ratio, waist-to-height ratio, waist circumference,
      hip circumference, and lipometry) of 100 BD individuals were compared with data
      of 57 matched mentally healthy controls. Additionally, fasting serum parameters
      including metabolic parameters and monoamines were analyzed. Findings indicate
      that similar to US BD cohorts, Austrian patients exhibit an increased central
      body fat accumulation (i.e., higher subcutaneous adipose tissue at upper abdomen)
      accompanying with the harmful IDF-defined metabolic syndrome. In addition,
      positive associations between epinephrine as well as staging and fat parameters
      were detected. 

PMID- 25381167
TI  - Shape does matter: short high-concentration exposure minimizes resistance
      emergence for fluoroquinolones in Pseudomonas aeruginosa.
AB  - OBJECTIVES: For fluoroquinolones, the area under the free plasma concentration
      time curve divided by the MIC (fAUC/MIC) best predicts bacterial killing in mice
      and outcomes in patients. However, it is unknown whether the shape of the
      antibiotic concentration profile affects resistance emergence. Our objective was
      to compare killing and resistance between ciprofloxacin concentration profiles
      with different shapes at the same fAUC/MIC and identify the durations of
      ciprofloxacin exposure that minimize resistance emergence. METHODS: Static time
      kill studies over 24 h using Pseudomonas aeruginosa ATCC 27853 assessed fAUC/MIC
      of 44 and 132 of ciprofloxacin (MICCIP = 0.25 mg/L) and fAUC/MIC of 22, 44 and
      132 of ciprofloxacin plus an efflux pump inhibitor (MICCIP+EPI = 0.031 mg/L) at
      initial inocula of 10(4), 10(5) and 10(6) cfu/mL. Ciprofloxacin was added at 0 h
      and rapidly removed at 1, 4, 10, 16 or 24 h. Mutant frequencies and MICs were
      determined at 24 h. RESULTS: High ciprofloxacin concentrations over 1-10 h
      yielded more rapid and extensive initial killing compared with 16 and 24 h
      exposures at the same fAUC/MIC. No resistance emerged for 1-10 h exposures,
      although regrowth of susceptible bacteria was extensive. Ciprofloxacin exposure
      over 24 h yielded less regrowth, but ciprofloxacin-resistant bacteria at 5* MIC
      amplified by over 5 log10 and almost completely replaced the susceptible bacteria
      by 24 h; MICs increased 4- to 8-fold. Resistance also emerged on 3* MIC, but not
      5* MIC, plates when efflux was inhibited. CONCLUSIONS: Pre-existing resistant
      subpopulations amplified extensively with 24 and 16 h exposures, but not with
      shorter durations. The shape of the ciprofloxacin concentration profile was
      critical to minimize resistance emergence.

PMID- 25381168
TI  - Molecular characterization of linezolid-resistant CoNS isolates in Japan.
AB  - OBJECTIVES: Linezolid has been reported to remain active against 98% of
      staphylococci with resistance identified in 0.05% of Staphylococcus aureus and
      1.4% of CoNS. The objective of this study was to characterize the linezolid
      resistance mechanisms in the linezolid-resistant CoNS strains isolated in Japan.
      METHODS: Staphylococcus capitis strains exhibiting linezolid MICs >8 mg/L
      isolated from inpatients between 2012 and 2014 were screened for cfr and
      mutations in 23S rRNA, L3 and L4 by PCR/sequencing. Isolates were also examined
      for mutations in the rlmN gene. RESULTS: S. capitis had six 23S rRNA alleles.
      Five S. capitis isolates displayed linezolid MICs of 8, 16 and 32 mg/L. G2576U
      mutations were detected in three, four or five copies of 23S rRNA in all
      isolates. In two isolates exhibiting the highest linezolid MIC (32 mg/L) there
      was a large deletion in a single copy of 23S rRNA. Repeated 10 bp sequences were
      found in both 16S and 23S rRNAs, suggesting deletion by recombination between the
      repeats. One isolate had the mutation Ala-142->Thr in the ribosomal protein L3.
      All linezolid-resistant isolates also demonstrated mutations in the gene encoding
      RlmN methyltransferase, leading to Thr-62->Met and Gly-148->Ser. CONCLUSIONS:
      Multiple mechanisms appeared to be responsible for the elevated linezolid
      resistance in S. capitis isolates: a G2576U mutation in different numbers of
      copies of 23S rRNA, loss of a single copy of 23S rRNA and a mutation in the
      ribosomal protein L3, suggesting the accumulation of independent mutational
      events.

PMID- 25381169
TI  - Identification of optimal renal dosage adjustments for high-dose extended
      infusion cefepime dosing regimens in hospitalized patients.
AB  - OBJECTIVES: The objective of this study was to identify optimal renal dose
      adjustments for 2 g of cefepime every 8 h as a 3 h infusion where the probability
      of target attainment was optimized and drug accumulation was minimal. METHODS:
      Embedded with a population pharmacokinetic model derived in a population of
      hospitalized patients with varying degrees of renal function, a series of 5000
      subject Monte Carlo simulations using ADAPT 5 were performed for 3 h infusions of
      2 g every 6, 8, 12 and 24 h. To assess exposure profiles across various levels of
      renal function, the estimated CLCR was fixed at values between 20 and 150 mL/min.
      For each regimen examined, the fraction of simulated subjects who achieved free
      drug concentrations in excess of the MIC for >=60% of the dosing interval (60% fT
      > MIC) at the various CLCR levels was determined and this information was used to
      identify optimal renal dose adjustments without profound drug exposure. RESULTS:
      In the Monte Carlo simulations, modification of the parent regimen (2 g every 8
      h) to 2 g every 6 h for CLCR >120 mL/min and extension of the dosing interval to
      every 12 and 24 h at CLCR of 60 and 20 mL/min, respectively, provided favourable
      probability of target attainment profiles without profound drug exposure.
      CONCLUSIONS: The findings from this study identified renal dose alteration
      regimens that yielded favourable pharmacodynamic profiles without excessive drug
      exposure. As these findings were based on mathematical models, they should be
      validated in the clinical arena.

PMID- 25381170
TI  - Mutagenic and cytotoxic activities of benfuracarb insecticide.
AB  - Benfuracarb is a carbamate insecticide used to control insect pests in vegetables
      and it has anti-acetylcholinesterase activity lower than other carbamates.
      Cytotoxic effects of benfuracarb were evaluated by using root growth inhibition
      (EC50), mitotic index (MI), and mitotic phase determinations on the root meristem
      cells of Allium cepa and mutagenic effects were determined in Salmonella
      typhymurium Ames test by TA98 and TA100 strains with and without metabolic
      activation. In Allium test, 1 % DMSO was used as negative control group and 10
      ppm MMS was used as positive control group. 75 ppm concentration of benfuracarb
      was found as EC50. In MI and mitotic phases determination study, 37.5, 75 and 150
      ppm doses of benfuracarb were used. Dose-dependent cytotoxic activity was found
      by root growth inhibition and MI studies. It was identified that mitotic
      inhibition activity of benfuracarb was higher than 10 ppm MMS. In Ames test,
      mutagenic activity was not observed and over 200 ug/plate of benfuracarb was
      determined as cytotoxic to S. typhymurium strains. Benfuracarb can be called as
      "mitotic inhibitor" but not called as mutagen. 

PMID- 25381172
TI  - Monte Carlo simulation of mixed nonionic Brij surfactants in water.
AB  - Nonionic surfactants such as the Brij(r) series are important in the preparation
      of transdermal drug nanodelivery products using nanoemulsions because of their
      low toxicity and low irritancy. Here, Monte Carlo (MC) simulation was used to
      examine the physical behavior of the model deterministic system by using sampling
      procedures. Metropolis MC simulations were run on three mixtures of two different
      nonionic surfactants, Brij92 and Brij96, with different compositions in aqueous
      solution. The system was simulated in the canonical ensemble with constant
      temperature, volume and number of molecules. Hence, the acceptance ratio for
      single atom moves of the mixed surfactants increased as the concentration of
      surfactants increased from 0.494 to 0.591. The lowest total energy for the mixed
      surfactant systems was -99,039 kcal mol(-1) due to the interaction between all
      molecules in the system simulated. The physicochemical properties of models such
      as the radius of gyration and radial distribution function, were also determined.
      These observations indicate that the behavior and physicochemical of mixed
      surfactant and PKOEs nanoemulsion systems were described adequately during the
      simulation. 

PMID- 25381171
TI  - Association between coenzyme Q10 and glucose transporter (GLUT1) deficiency.
AB  - BACKGROUND: It has been demonstrated that glucose transporter (GLUT1) deficiency
      in a mouse model causes a diminished cerebral lipid synthesis. This deficient
      lipid biosynthesis could contribute to secondary CoQ deficiency. We report here,
      for the first time an association between GLUT1 and coenzyme Q10 deficiency in a
      pediatric patient. CASE PRESENTATION: We report a 15 year-old girl with truncal
      ataxia, nystagmus, dysarthria and myoclonic epilepsy as the main clinical
      features. Blood lactate and alanine values were increased, and coenzyme Q10 was
      deficient both in muscle and fibroblasts. Coenzyme Q10 supplementation was
      initiated, improving ataxia and nystagmus. Since dysarthria and myoclonic
      epilepsy persisted, a lumbar puncture was performed at 12 years of age disclosing
      diminished cerebrospinal glucose concentrations. Diagnosis of GLUT1 deficiency
      was confirmed by the presence of a de novo heterozygous variant (c.18+2T>G) in
      the SLC2A1 gene. No mutations were found in coenzyme Q10 biosynthesis related
      genes. A ketogenic diet was initiated with an excellent clinical outcome.
      Functional studies in fibroblasts supported the potential pathogenicity of
      coenzyme Q10 deficiency in GLUT1 mutant cells when compared with controls.
      CONCLUSION: Our results suggest that coenzyme Q10 deficiency might be a new
      factor in the pathogenesis of G1D, although this deficiency needs to be confirmed
      in a larger group of G1D patients as well as in animal models. Although ketogenic
      diet seems to correct the clinical consequences of CoQ deficiency, adjuvant
      treatment with CoQ could be trialled in this condition if our findings are
      confirmed in further G1D patients.

PMID- 25381173
TI  - Effects of detraining after blood flow-restricted low-intensity concentric or
      eccentric training on muscle size and strength.
AB  - We investigated the effects of 6 weeks of detraining on muscle size and strength
      in young men who had previously participated in 6 weeks (3 days/week) of 30 % of
      concentric one-repetition maximal (1-RM) dumbbell curl training [one arm:
      concentric blood flow restricted (BFR) exercise (CON-BFR); the other arm:
      eccentric BFR exercise (ECC-BFR)]. MRI-measured muscle cross-sectional area (CSA)
      at 10 cm above the elbow joint increased from pre to post (p < 0.01), and the
      muscle CSA following detraining remained greater than pre (p < 0.01) but was
      similar to that observed at post. Maximal voluntary contraction (MVC) increased
      from pre to post (p < 0.05), and the MVC following detraining remained greater
      than pre (p < 0.05) but was similar to that observed at post. The ECC-BFR did not
      produce any changes across time. Increased muscle strength following 6 weeks of
      CON-BFR was well preserved at 6 weeks of detraining, which may be primarily
      related to muscle hypertrophy.

PMID- 25381174
TI  - Ethyl 3,4-dihydroxy benzoate, a unique preconditioning agent for alleviating
      hypoxia-mediated oxidative damage in L6 myoblasts cells.
AB  - The importance of hypoxia inducible factor (HIF) as the master regulator of
      hypoxic responses is well established. Oxygen-dependent prolyl hydroxylase domain
      enzymes (PHDs) negatively regulate HIF directing it to the path of degradation
      under normoxia and are, consequently, attractive therapeutic targets. Inhibition
      of PHDs might upregulate beneficial HIF-mediated processes. In this study, we
      have examined the efficacy of PHD inhibitor ethyl 3,4-dihydroxy benzoate (EDHB)
      in affording protection against hypoxia-induced oxidative damage in L6 myoblast
      cells. L6 cells were exposed to hypoxia (0.5 % O2) after preconditioning with
      EDHB for different times. Levels of HIF-1alpha, oxidative stress and antioxidant
      status were measured after hypoxia exposure. Preconditioning with EDHB
      significantly improved cellular viability, and the diminished levels of protein
      oxidation and malondialdehyde indicated a decrease in oxidative stress when
      exposed to hypoxia. EDHB treatment also conferred enhanced anti-oxidant status,
      as there was an increase in the levels of glutathione and antioxidant enzymes
      like superoxide dismutase and glutathione peroxidase. Further, augmentation of
      the levels of HIF-1alpha boosted protein expression of antioxidative enzyme heme
      oxygenase I. There was enhanced expression of metallothioneins which also have
      antioxidant, anti-inflammatory properties. These results thus accentuate the
      potential cytoprotective efficacy of EDHB against hypoxia-induced oxidative
      damage. 

PMID- 25381176
TI  - Erratum to: Newborn Screening for Galactosemia in the United States: Looking
      Back, Looking Around, and Looking Ahead.

PMID- 25381175
TI  - Current state of the art, multimodality research and future visions for the
      treatment of patients with prostate cancer: consensus results from "Challenges
      and Chances in Prostate Cancer Research Meeting 2013".
AB  - A brainstorming and consensus meeting organized by the German Cancer Aid focused
      on modern treatment of prostate cancer and promising innovative techniques and
      research areas. Besides optimization of screening algorithms, molecular-based
      stratification and individually tailored treatment regimens will be the future of
      multimodal prostate cancer management. Effective interdisciplinary structures,
      including biobanking and data collection mechanisms are the basis for such
      developments. 

PMID- 25381179
TI  - Velocity mapping of the aortic flow at 9.4 T in healthy mice and mice with
      induced heart failure using time-resolved three-dimensional phase-contrast MRI
      (4D PC MRI).
AB  - OBJECTIVES: In this study, we established and validated a time-resolved three
      dimensional phase-contrast magnetic resonance imaging method (4D PC MRI) on a 9.4
      T small-animal MRI system. Herein we present the feasibility of 4D PC MRI in
      terms of qualitative and quantitative flow pattern analysis in mice with
      transverse aortic constriction (TAC). MATERIALS AND METHODS: 4D PC FLASH images
      of a flow phantom and mouse heart were acquired at 9.4 T using a four-point phase
      encoding scheme. The method was compared with slice-selective PC FLASH and
      ultrasound using Bland-Altman analysis. Advanced 3D streamlines were visualized
      utilizing Voreen volume-rendering software. RESULTS: In vitro, 4D PC MRI flow
      profiles showed the transition between laminar and turbulent flow with increasing
      velocities. In vivo, 4D PC MRI data of the ascending aorta and the pulmonary
      artery were confirmed by ultrasound, resulting in linear regressions of R (2) >
      0.93. Magnitude- and direction-encoded streamlines differed substantially pre-
      and post-TAC surgery. CONCLUSIONS: 4D PC MRI is a feasible tool for in vivo
      velocity measurements on high-field small-animal scanners. Similar to clinical
      measurement, this method provides a complete spatially and temporally resolved
      dataset of the murine cardiovascular blood flow and allows for three-dimensional
      flow pattern analysis.

PMID- 25381180
TI  - Fast PRF-based MR thermometry using double-echo EPI: in vivo comparison in a
      clinical hyperthermia setting.
AB  - OBJECTIVE: To develop and test in a clinical setting a double-echo segmented echo
      planar imaging (DEPI) pulse sequence for proton resonance frequency (PRF)-based
      temperature monitoring that is faster than conventional PRF thermometry pulse
      sequences and not affected by thermal changes in tissue conductivity. MATERIALS
      AND METHODS: Four tumor patients underwent between one and nine magnetic
      resonance (MR)-guided regional hyperthermia treatments. During treatment, the
      DEPI sequence and a FLASH PRF sequence were run in an interleaved manner to
      compare the results from both sequences in the same patients and same settings.
      Temperature maps were calculated based on the phase data of both sequences.
      Temperature measurements of both techniques were compared using Passing and
      Bablok regression and the Bland-Altman method. RESULTS: The temperature results
      from the DEPI and FLASH sequences, on average, do not differ by more than DeltaT
      = 1  degrees C. DEPI images showed typically more artifacts and approximately a
      twofold lower signal-to-noise ratio (SNR), but a sufficient temperature precision
      of 0.5 degrees , which would theoretically allow for a fivefold higher frame
      rate. CONCLUSION: The results indicate that DEPI can replace slower temperature
      measurement techniques for PRF-based temperature monitoring during thermal
      treatments. The higher acquisition speed can be exploited for hot spot
      localization during regional hyperthermia as well as for temperature monitoring
      during fast thermal therapies.

PMID- 25381181
TI  - Free breathing 1H MRI of the human lung with an improved radial turbo spin-echo.
AB  - OBJECTIVE: To optimize a radial turbo spin-echo sequence for motion-robust
      morphological lung magnetic resonance imaging (MRI) in free respiration.
      MATERIALS AND METHODS: A versatile multi-shot radial turbo spin-echo (rTSE)
      sequence is presented, using a modified golden ratio-based reordering designed to
      prevent coherent streaking due to data inconsistencies from physiological motion
      and the decaying signal. The point spread function for a moving object was
      simulated using a model for joint respiratory and cardiac motion with a
      concomitant T2 signal decay and with rTSE acquisition using four different
      reordering techniques. The reordering strategies were compared in vivo using
      healthy volunteers and the sequence was tested for feasibility in two patients
      with lung cancer and pneumonia. RESULTS: Simulations and in vivo measurements
      showed very weak artifacts, aside from motion blur, using the proposed
      reordering. Due to the opportunity for longer scan times in free respiration, a
      high signal-to-noise ratio (SNR) was achieved, facilitating identification of the
      disease as compared to standard half-Fourier-acquisition single-shot turbo spin
      echo (HASTE) scans. Additionally, post-processing allowed modifying the T2
      contrast retrospectively, further improving the diagnostic fidelity. CONCLUSION:
      The proposed radial TSE sequence allowed for high-resolution imaging with limited
      obscuring artifacts. The radial k-space traversal allowed for versatile post
      processing that may help to improve the diagnosis of subtle diseases.

PMID- 25381182
TI  - Gartland type III supracondylar humerus fractures: outcome and complications as
      related to operative timing and pin configuration.
AB  - PURPOSE: Supracondylar fractures of the humerus are the most common fracture of
      the elbow in children. The purpose of this study was to evaluate, in terms of
      outcomes and complications, Gartland type III pediatric supracondylar humerus
      fractures treated at a pediatric level-one trauma center over a 7-year period,
      specifically addressing the impact of time to surgery on the incidence of
      complications and conversion to open reduction. METHODS: We retrospectively
      reviewed 297 pediatric patients that sustained a closed Gartland type III
      supracondylar humerus fracture treated between December 2004 and December 2011.
      The time to the operating room was calculated from the medical records for each
      patient. The outcome measures evaluated were operative time, conversion to open
      procedure, and perioperative and postoperative complications. RESULTS: In our
      study, there were 30 complications in 25 children (8.4%). Conversion to open
      reduction occurred in 28 children (9.4%). The time from the emergency department
      to the operating room was not significantly correlated with increased
      complications, increased operative time, or conversion to open reduction (p >
      0.05). Crossed pinning resulted in an increased risk of overall complications
      [odds ratio (OR) = 2.6] and iatrogenic nerve injuries (OR = 9.3). Complications
      also occurred more commonly in boys (OR = 3.3) and in older patients (p = 0.0069)
      CONCLUSIONS: We found no significant correlation between the time to surgery and
      complications, operative time, or need for open reduction. These findings support
      the trend of treating Gartland type III supracondylar humerus fractures in a less
      urgent manner. In addition, our study supports the concept that cross pinning
      leads to more complications than lateral pinning, including an 8-fold increase in
      iatrogenic nerve injury.

PMID- 25381184
TI  - Anti-vibration gloves?
AB  - For exposure to hand-transmitted vibration (HTV), personal protective equipment
      is sold in the form of anti-vibration (AV) gloves, but it remains unclear how
      much these gloves actually reduce vibration exposure or prevent the development
      of hand-arm vibration syndrome in the workplace. This commentary describes some
      of the issues that surround the classification of AV gloves, the assessment of
      their effectiveness and their applicability in the workplace. The available
      information shows that AV gloves are unreliable as devices for controlling HTV
      exposures. Other means of vibration control, such as using alternative production
      techniques, low-vibration machinery, routine preventative maintenance regimes,
      and controlling exposure durations are far more likely to deliver effective
      vibration reductions and should be implemented. Furthermore, AV gloves may
      introduce some adverse effects such as increasing grip force and reducing manual
      dexterity. Therefore, one should balance the benefits of AV gloves and their
      potential adverse effects if their use is considered. 

PMID- 25381183
TI  - Alleviating waiting impulsivity and perseverative responding by MU-opioid
      receptor antagonism in two inbred mouse strains.
AB  - RATIONALE: Recent evidence has implicated the opioid system in exaggerated
      ethanol consumption and impulsivity deficits. The opioid receptor antagonist
      naltrexone (NTX) has proven efficient in reducing alcohol consumption; however,
      its role on impulsive behaviour is not fully characterised. OBJECTIVE: The aim of
      this study was to investigate the effects of NTX on two measures of impulsive
      behaviour in two inbred mouse strains that differ in ethanol preference and
      impulsive phenotype. METHODS: Two separate groups of C57BL/6J (B6, n = 24) and
      DBA2/J (D2, n = 24) male mice were exposed to intermittent ethanol (IEE; 2 g/kg)
      during early (PND 30-45, IEE_Early) or late (PND 45-60, IEE_Late) adolescence or
      the respective saline control. The ability of NTX (10 mg/kg) alone, or co
      administered with ethanol (0.5 g/kg), to diminish waiting impulsivity in the five
      choice serial reaction time task (5-CSRTT), or improve decision-making in a mouse
      version of the Iowa Gambling Task (mIGT), was examined in adulthood. RESULTS: In
      the 5-CSRTT, NTX diminished impulsivity in both strains of mice, irrespective of
      previous ethanol experience. In the mIGT, NTX failed to alter risky decision
      making but decreased perseverative responding. CONCLUSIONS: Blocking the actions
      of endogenous opioids may attenuate waiting impulsivity, in addition to
      alleviating perseverative responding. In a broader context, MU-opiate antagonism
      may be of potential interest for impulse-control disorders.

PMID- 25381185
TI  - Laboratory and workplace assessments of rivet bucking bar vibration emissions.
AB  - Sheet metal workers operating rivet bucking bars are at risk of developing hand
      and wrist musculoskeletal disorders associated with exposures to hand-transmitted
      vibrations and forceful exertions required to operate these hand tools. New
      bucking bar technologies have been introduced in efforts to reduce workplace
      vibration exposures to these workers. However, the efficacy of these new bucking
      bar designs has not been well documented. While there are standardized laboratory
      based methodologies for assessing the vibration emissions of many types of
      powered hand tools, no such standard exists for rivet bucking bars. Therefore,
      this study included the development of a laboratory-based method for assessing
      bucking bar vibrations which utilizes a simulated riveting task. With this
      method, this study evaluated three traditional steel bucking bars, three
      similarly shaped tungsten alloy bars, and three bars featuring spring-dampeners.
      For comparison the bucking bar vibrations were also assessed during three typical
      riveting tasks at a large aircraft maintenance facility. The bucking bars were
      rank-ordered in terms of unweighted and frequency-weighted acceleration measured
      at the hand-tool interface. The results suggest that the developed laboratory
      method is a reasonable technique for ranking bucking bar vibration emissions; the
      lab-based riveting simulations produced similar rankings to the workplace
      rankings. However, the laboratory-based acceleration averages were considerably
      lower than the workplace measurements. These observations suggest that the
      laboratory test results are acceptable for comparing and screening bucking bars,
      but the laboratory measurements should not be directly used for assessing the
      risk of workplace bucking bar vibration exposures. The newer bucking bar
      technologies exhibited significantly reduced vibrations compared to the
      traditional steel bars. The results of this study, together with other
      information such as rivet quality, productivity, tool weight, comfort, worker
      acceptance, and initial cost can be used to make informed bucking bar selections.

PMID- 25381186
TI  - Description and evaluation of a hearing conservation program in use in a
      professional symphony orchestra.
AB  - Professional orchestral musicians risk permanent hearing loss while playing their
      instruments. Protecting the hearing of these musicians in the workplace is
      critical to their ongoing ability to play their instruments, but typical
      workplace hearing conservation measures can have very damaging effects on the
      product (music) and the musicians' abilities to hear one another sufficiently. To
      enable effective intervention, orchestras as employers must encourage engagement
      with hearing protection programs and implement controls while preserving the
      integrity of the music. To achieve this, typical approaches used in other
      industries must be redesigned to suit this unique workplace. In response to these
      challenges, the Queensland Symphony Orchestra (Brisbane, Australia) introduced a
      comprehensive hearing conservation strategy in 2005 based upon best practice at
      the time. This strategy-which has been regularly refined-continues to be
      implemented on a daily basis. This investigation aimed to assess the successes,
      difficulties, and practical viability of the program. To achieve this a process
      evaluation was carried out, incorporating archival analyses, player and
      management focus groups, and an interview with the program's administrator.
      Results show the program has successfully become integrated into the orchestra's
      and the musicians' daily operations and significantly contributes to managing the
      risk of hearing loss in this population. While there is room for improvement in
      the orchestra's approach-particularly regarding usable personal protective
      devices and improved education and training, results are encouraging. This study
      provides a basis for those wishing to implement or evaluate similar paradigms.

PMID- 25381187
TI  - Methionine production--a critical review.
AB  - This paper presents an updated critical review about several attempts to
      contribute methionine (Met) to the world market with an emphasis on fermentation
      processes, especially from natural biological sources. Analytical methods for the
      determination of methionine are reviewed as well as applications in feed, food,
      pharmacy, and medicine. Fermentation studies published within the last five
      decades are elucidated critically, mainly with respect to the sulfur balance,
      substrate yield, and the analytical validity. From all the published fermentation
      data, it can be concluded that up to now no more than 5 g/L methionine are
      achievable without using genetically modified organisms (GMOs). The highest L
      methionine concentration from natural sources reached so far amounts to 35 g/L
      and is published as a patent using a GMO of Escherichia coli. The review closes
      with a comprehensive overview of the role and activities of global methionine
      manufacturers. Some current market data is also presented.

PMID- 25381188
TI  - Redistribution of acetyl groups on the non-reducing end xylopyranosyl residues
      and their removal by xylan deacetylases.
AB  - BACKGROUND: Monoacetylated xylosyl residues of the main hardwood hemicellulose
      acetylglucuronoxylan undergo acetyl group migration between positions 2 and 3,
      and predominantly to position 4 of the non-reducing end xylopyranosyl (NRE-Xylp)
      residues which are amplified by saccharifying enzymes. On monoacetylated non
      reducing end xylopyranosyl (NRE-Xylp) residues of xylooligosaccharides the acetyl
      group migrates predominantly to position 4 and hinders their hydrolysis by beta
      xylosidase. METHODS: Acetyl migration on the NRE-Xylp residues and their
      enzymatic deacetylation by various xylan deacetylases was followed by (1)H-NMR
      spectroscopy and TLC. RESULTS: A 5-min heat treatment of 4-nitrophenyl 3-O-acetyl
      beta-D-xylopyranoside was sufficient to establish equilibrium between monoacetate
      derivatives acetylated at positions 2, 3 and 4. Rapid acetyl migration along the
      NRE-Xylp ring at elevated temperature was confirmed in derivatives of methyl beta
      1,4-xylotrioside (Xyl3Me) monoacetylated solely on the NRE-Xylp residue, the
      analogues of naturally occurring acetylated xylooligosaccharides. The Xyl3Me
      monoacetates were used as substrates to study regioselectivity of the NRE-Xylp
      residue deacetylation by various acetylxylan esterases (AcXEs) of distinct
      carbohydrate esterase (CE) families. CE1, CE4 and CE6 AcXEs hydrolyzed
      considerably faster the 2"-O-acetyl derivative than the 3"-O-acetyl derivative.
      In contrast, the CE16 acetyl esterase preferred to attack the ester bond at
      position 3 followed by position 4. CONCLUSIONS: Redistribution of acetyl group on
      the NRE-Xylp residues is extremely rapid at elevated temperature and includes the
      formation of 4-acetate. Regioselectivity of AcXEs and CE16 acetyl esterase on
      these monoacetates is complementary. GENERAL SIGNIFICANCE: The formation of all
      isomers of acetylated xylosyl residues must be taken into account after a long
      term incubation of acetylxylan and acetylated xylooligosaccharides solutions or
      upon their treatment at elevated temperatures. This phenomenon emphasizes
      requirement of both types of xylan deacetylases to enable a rapid
      saccharification of xylooligosaccharides by glycoside hydrolases.

PMID- 25381189
TI  - The effects of Reiki therapy and companionship on quality of life, mood, and
      symptom distress during chemotherapy.
AB  - This pilot study examined the effects of Reiki therapy and companionship on
      improvements in quality of life, mood, and symptom distress during chemotherapy.
      Thirty-six breast cancer patients received usual care, Reiki, or a companion
      during chemotherapy. First, data were collected from patients receiving usual
      care. Second, patients were randomized to either receive Reiki or a companion
      during chemotherapy. Questionnaires assessing quality of life, mood, symptom
      distress, and Reiki acceptability were completed at baseline and chemotherapy
      sessions 1, 2, and 4. Reiki was rated relaxing with no side effects. Reiki and
      companion groups reported improvements in quality of life and mood that were
      greater than those seen in the usual care group. Interventions during
      chemotherapy, such as Reiki or companionship, are feasible, acceptable, and may
      reduce side effects. 

PMID- 25381190
TI  - Limonoid and Steroidal Saponin from Azadirachta indica.
AB  - A new limonoid, 17-(5-methoxy-2-oxofuran-3-yl)-28-deoxonimbolide (1), and a new
      C21 steroidal saponin, 2alpha,4alpha-dihydroxy-pregn-5-en-16-one-3alpha-O-D
      glucopyranoside (2), together with 11 known compounds were isolated from the
      methanol extract of the leaves of Azadirachta indica. The structures were
      elucidated by means of spectroscopic analysis and putative biosynthetic origins.
      All the compounds were evaluated for their antibacterial activities against six
      bacterial strains. 

PMID- 25381192
TI  - The use of grammatical morphemes by Mandarin-speaking children with high
      functioning autism.
AB  - The present study investigated the production of grammatical morphemes by
      Mandarin-speaking children with high functioning autism. Previous research found
      that a subgroup of English-speaking children with autism exhibit deficits in the
      use of grammatical morphemes that mark tense. In order to see whether this
      impairment in grammatical morphology can be generalised to children with autism
      from other languages, the present study examined whether or not high-functioning
      Mandarin-speaking children with autism also exhibit deficits in using grammatical
      morphemes that mark aspect. The results show that Mandarin-speaking children with
      autism produced grammatical morphemes significantly less often than age-matched
      and IQ-matched TD peers as well as MLU-matched TD peers. The implications of
      these findings for understanding the grammatical abilities of children with
      autism were discussed. 

PMID- 25381191
TI  - The Influence of Task Difficulty and Participant Age on Balance Control in ASD.
AB  - Impairments in sensorimotor integration are reported in Autism Spectrum Disorder
      (ASD). Poor control of balance in challenging balance tasks is one suggested
      manifestation of these impairments, and is potentially related to ASD symptom
      severity. Reported balance and symptom severity relationships disregard age as a
      potential covariate, however, despite its involvement in balance development. We
      tested balance control during increasingly difficult balance conditions in
      children with ASD and typically developing peers, and investigated relationships
      between balance control and diagnostic/symptom severity metrics for participants
      with ASD, including age as a covariate. Balance deficits in ASD were exacerbated
      by stance alterations, but were not related to symptom severity when age was
      considered. These findings support impaired balance in ASD, especially in
      challenging conditions, but question a link between balance and symptom severity.

PMID- 25381194
TI  - Incidence of type 1 diabetes among Polish children ages 0-14 years from 1989
      2012.
AB  - AIMS: The incidence of pediatric type 1 diabetes mellitus (T1DM) in Poland is
      intermediate relative to the rest of the world. T1DM prevalence in the region of
      Silesia approximates national estimates for all of Poland. This epidemiologic
      study aimed to analyze the changes in incidence rates of T1DM among children ages
      0-14 years from 1989 to 2012 in this region. METHODS: Data collection methods for
      the registry followed EURODIAB criteria. To estimate overall population size,
      data from the Central and regional Statistical Office in Katowice were used. T1DM
      incidence rates/100,000 children ages 0-14 years/annum and their 95 % CI were
      calculated for all children and in age subgroups (0-4, 5-9, 10-14 years). For
      comparative analysis incidence rates were age and sex standardized to the
      population of Poland in 2005. For statistical analyses open source R Bioconductor
      software was used. RESULTS: During this 24-year period, 2,215 new cases (1,146
      boys) were diagnosed. The standardized incidence rate rose about 7 % annually.
      The mean standardized incidence rates estimated in four 6-year time periods (1989
      1994, 1995-2000, 2001-2006, 2007-2012) separately showed significant increases
      from 5.80/100,000/year (1989-1994) through 10.44/100,000/year (1995-2000) and
      15.05/100,000/year (2001-2006) to 18.94/100,000/year (2007-2012). From 1989 to
      2012, the greatest relative rise in annual incidence (/100,000/year) was among
      the very young: 2.58-14.00 (0-4 years); 4.96-19.43 (5-9 years); 8.84-22.15 (10-14
      years). The highest average annual increment of the incidence rate was in the
      middle age subgroup (5-9 years). No significant sex difference was observed.
      CONCLUSIONS: The overall incidence rate increased 3.8 times, suggesting an
      epidemic of pediatric T1DM in Silesia, Poland. These temporal changes confirm
      that Poland currently has one of the highest incidence rates of pediatric T1DM in
      Europe.

PMID- 25381193
TI  - Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes
      and complicates secondary prevention.
AB  - AIMS: Non-diabetic children with multiple islet autoantibodies were recruited to
      a secondary prevention trial. The objective was to determine the predictive value
      of baseline (1) HbA1c and metabolic variables derived from intravenous (IvGTT)
      and oral glucose tolerance tests (OGTT), (2) insulin resistance and (3) number,
      type and levels of islet autoantibodies, for progression to type 1 diabetes.
      METHODS: Children [n = 50, median 5.1 (4-17.9) years] with autoantibodies to
      glutamate decarboxylase (GAD65A) and at least one of insulinoma-associated
      protein 2 (IA-2A), insulin or ZnT8 transporter (ZnT8RA, ZnT8WA, ZnT8QA) were
      screened with IvGTT and OGTT and followed for a minimum of 2 years. RESULTS:
      Baseline first phase insulin response (sum of serum-insulin at 1 and 3 min during
      IvGTT; FPIR) <=3 MUU/mL [HR 4.42 (CI 1.40-14.0) p = 0.011] and maximal plasma
      glucose >=11.1 mmol/L measured at 30, 60 and/or 90 min during OGTT [HR 6.13 (CI
      1.79-21.0) p = 0.0039] were predictors for progression to diabetes. The
      combination of FPIR from IvGTT and maximal plasma glucose during OGTT predicted
      diabetes in 10/12 children [HR 9.17 (CI 2.0-42.0) p = 0.0043]. High-level IA-2A,
      but not number of autoantibodies, correlated to dysglycemia during OGTT (p =
      0.008) and to progression to type 1 diabetes [HR 4.98 (CI 1.09-22.0) p = 0.039].
      CONCLUSIONS: Baseline FPIR, maximal plasma glucose >=11.1 at 30, 60 or 90 min
      during OGTT and high-level IA-2A need to be taken into account when randomizing
      islet autoantibody positive non-diabetic children to secondary prevention.

PMID- 25381195
TI  - Postmortem angiography using femoral cannulation and postmortem microbiology.
AB  - Despite the undeniable advantages of postmortem angiography, numerous questions
      have arisen concerning the influence that the injected contrast media may
      exercise on biological fluids and tissues collected for toxicological and
      biochemical investigations. Moreover, cardiac blood for microbiological
      investigations cannot be obtained post-angiography. In this study, we examined
      whether the peripheral blood collected prior to postmortem angiography, using
      percutaneous access to femoral vessels after skin surface disinfection, could be
      suitable for microbiological investigations when postmortem angiography with
      femoral vessel cannulation is also performed. A total of 66 cases were included
      in the study and were divided into two subgroups (angiography and bacteriology
      group, 33 cases and control group, 33 cases). Autopsies, histology, toxicology,
      bacteriology, and biochemical investigations (procalcitonin, C-reactive protein,
      interleukin-6, and soluble triggering receptors expressed on myeloid cells type
      1) were performed in all cases. No statistically significant differences between
      the two groups were noted, and identified category distribution (death unrelated
      to infection, true infection, false positive, and undetermined) was rather
      similar in both studied populations. These preliminary results suggest that
      postmortem angiography using a femoral approach does not constitute an impediment
      to the collection of peripheral blood for microbiology and vice versa. Moreover,
      the use of femoral blood for microbiology does not lead to an increased risk of
      doubtful results. 

PMID- 25381196
TI  - Development and validation of a rapid PCR method for the PowerPlex(r) 16 HS
      system for forensic DNA identification.
AB  - Currently, the amplification step of most forensic DNA profiling systems takes 3
      4 h to complete. A decrease in the amplification time would allow for increased
      laboratory throughput, which may help reduce backlog when is due to limited
      cycling capacity. By using the SpeedSTARTM HS Polymerase (Takara Bio, Otsu,
      Japan) in combination with the Veriti(r) (Applied Biosystems, Foster City, CA,
      USA) rapid thermal cycler, the amplification time for the PowerPlex(r) 16 HS
      (Promega, Madison, WI, USA) kit was reduced by 66% (1 h). The sensitivity of this
      fast method was comparable to the standard system (0.13 ng). Although this rapid
      protocol showed an increase in average stutter ratios (2.8%) and a decrease in
      average peak height ratios (7%) across all loci when compared with standard
      conditions, it was able to consistently generate reliable DNA profiles. The
      results of this study indicate that the rapid protocol could be implemented in
      forensic laboratories with an optimal range of 0.25-2 ng of input DNA using
      appropriate analytical interpretation guidelines.

PMID- 25381198
TI  - A Race Model for Responses and Response Times in Tests.
AB  - Latent trait models for responses and response times in tests are often pure
      statistical models without a close connection to features of the assumed response
      process. In the present paper, a new model is presented that is more closely
      related to assumptions about the response process. The model is based on two
      increasing stochastic processes. Each stochastic process represents the
      accumulation of knowledge with respect to one of two response options, the
      correct and incorrect response. Both accumulators compete and the accumulator
      that first exceeds a critical level determines the response. General assumptions
      about the accumulators result in a race between two response times that follow a
      bivariate Birnbaum Saunders distribution. The model can be calibrated with
      marginal maximum likelihood estimation. Feasibility of the estimation approach is
      demonstrated in a simulation study. Additionally, a test of model fit is
      proposed. Finally, the model will be used for the analysis of an empirical data
      set. 

PMID- 25381199
TI  - Photoinduced processes in nucleic acids.
AB  - Photoinduced processes in nucleic acids are phenomena of fundamental interest in
      diverse fields, from prebiotic studies, through medical research on
      carcinogenesis, to the development of bioorganic photodevices. In this
      contribution we survey many aspects of the research across the boundaries.
      Starting from a historical background, where the main milestones are identified,
      we review the main findings of the physical-chemical research of photoinduced
      processes on several types of nucleic-acid fragments, from monomers to duplexes.
      We also discuss a number of different issues which are still under debate. 

PMID- 25381197
TI  - An argument for mechanism-based statistical inference in cancer.
AB  - Cancer is perhaps the prototypical systems disease, and as such has been the
      focus of extensive study in quantitative systems biology. However, translating
      these programs into personalized clinical care remains elusive and incomplete. In
      this perspective, we argue that realizing this agenda-in particular, predicting
      disease phenotypes, progression and treatment response for individuals-requires
      going well beyond standard computational and bioinformatics tools and algorithms.
      It entails designing global mathematical models over network-scale configurations
      of genomic states and molecular concentrations, and learning the model parameters
      from limited available samples of high-dimensional and integrative omics data. As
      such, any plausible design should accommodate: biological mechanism, necessary
      for both feasible learning and interpretable decision making; stochasticity, to
      deal with uncertainty and observed variation at many scales; and a capacity for
      statistical inference at the patient level. This program, which requires a close,
      sustained collaboration between mathematicians and biologists, is illustrated in
      several contexts, including learning biomarkers, metabolism, cell signaling,
      network inference and tumorigenesis.

PMID- 25381200
TI  - Primary percutaneous coronary intervention and bleeding risk in the era of drug
      eluting stent: a long-term cohort study.
AB  - Data of long-term efficacy and safety including bleeding risk associated with
      antithrombotic regimens after primary percutaneous coronary intervention (PCI)
      using first-generation drug-eluting stent (1st DES) are scarce. Consecutive 422
      patients with ST-elevation myocardial infarction (STEMI) underwent primary PCI
      with DES (285 patients), bare metal stent (BMS, 58 patients) or balloon
      angioplasty (BA 79 patients). At a median follow-up of 44 months, major
      cardiovascular events were significantly lower for 1st DES compared with BMS and
      BA (11.9 vs. 25.9 vs. 16.5 %, p = 0.027). Cardiac death, recurrent myocardial
      infarction and target lesion revascularization (TLR), differed among the groups
      (DES 8.8 %; BMS 13.8 %; BA 17.7 %; p = 0.019), although the superiority of DES
      subsided beyond 1 year by increased late TLRs. Major bleedings were not higher in
      DES than in BMS and BA (4.6 vs. 6.9 vs. 1.5 %, p = 0.252). Multivariate logistic
      regression analysis revealed that both dual antiplatelet therapy (DAPT) >24
      months and indefinite oral anticoagulation (OAC) were associated with a major
      bleeding. The risk was even greater with triple antithrombotic therapy (odds
      ratio 19.5; 95 % confidence interval 3.73-102.07; p < 0.0001). 1st DES showed
      favorable overall long-term clinical outcome in STEMI, with an inherent
      limitation of an increased risk of late TLR. Prolonged DAPT and OAC
      synergistically increase the risk of major bleeding after primary PCI. 

PMID- 25381201
TI  - Evidence for heightened hexokinase II immunoexpression in hepatocyte dysplasia
      and hepatocellular carcinoma.
AB  - BACKGROUND: Normal hepatocytes exhibit low-affinity hexokinase (glucokinase
      [HKIV]), but during oncogenesis, there is a switch from HKIV to HKII expression.
      The aims of this study were to compare the immunoexpression of HKII in non
      dysplastic cirrhosis (NDC), liver cell change/dysplasia in cirrhosis (LCD), HCC,
      and normal liver control tissues, and to correlate HKII expression with clinical
      and histopathological parameters. DESIGN: Immunohistochemistry was performed on a
      liver cancer progression tissue array consisting of specimens from explants with
      cirrhosis, including 45 tissue samples with HCC, 108 without HCC, 143 with LCD,
      and 8 normal liver control tissues. HKII expression was quantified as positive
      pixel counts/square millimeter (ppc/mm(2)) by image analysis. RESULTS: There was
      a stepwise increase in HKII level from normal liver tissue to NDC, to LCD, and to
      HCC (p = 0.001). HKII levels were significantly higher in areas of LCD versus NDC
      (p <= 0.001), and in LCD and HCC versus NDC (p = 0.007). HKII levels were similar
      in LCD and HCC (p = 0.124). HKII levels were higher in grade 2-4 versus grade 1
      HCCs (p = 0.044), and in pleomorphic versus non-pleomorphic HCC variants (p =
      0.041). Higher levels of HKII expression in LCD and HCC versus NDC and in higher
      tumor grade remained significant in multivariate analysis. CONCLUSIONS: Higher
      levels of HKII immunoexpression in LDC and HCC compared with NDC suggest that
      upregulation of HKII occurs during the process of hepatocarcinogenesis in humans.
      In HCC, higher levels of HKII are associated with more aggressive histological
      features.

PMID- 25381202
TI  - Withdrawal of long-term maintenance treatment with azathioprine tends to increase
      relapse risk in patients with Crohn's disease.
AB  - BACKGROUND AND AIM: Many patients with quiescent Crohn's disease are maintained
      on long-term treatment with azathioprine (AZA), but controlled data are limited.
      We aimed to evaluate the efficacy of AZA therapy for more than 4 years to
      maintain clinical remission. METHODS: We performed a randomized double-blind
      placebo-controlled AZA withdrawal trial with a follow-up period of 24 months.
      Patients had to have continuous AZA therapy >= 4 years without exacerbation of
      disease during the 12 months before enrollment, and a Crohn's disease activity
      index < 150 at baseline. Patients were randomized to continue on AZA or switch to
      placebo. The primary endpoint was time to clinical relapse during follow-up.
      RESULTS: After inclusion of 52 patients, the trial was stopped prematurely due to
      slow recruitment. During the 2-year follow-up, clinical relapse occurred in 4 of
      26 (15 %) patients on continued AZA and in 8 of 26 (31 %) patients on placebo.
      Time to clinical relapse averaged 22.3 months (95 % CI 20.6-24.0) on AZA and 19.2
      months (95 % CI 16.4-22.1) on placebo (p = 0.20). According to life-table
      analysis, the proportion of patients in remission after 12 and 24 months was 96
      +/- 4 and 86 +/- 7 % in patients receiving AZA versus 76 +/- 8 and 68 +/- 9 % in
      patients receiving placebo (month 12, p = 0.035; month 24, p = 0.30). A higher
      AZA dose at enrollment was an independent predictor for relapse (p < 0.05).
      CONCLUSIONS: AZA withdrawal resulted in a significantly increased relapse risk
      after 1 year and a nonstatistically significant trend for relapse after 2 years.
      Our results are in line with previous observations.

PMID- 25381204
TI  - Radiation therapy-induced aortoesophageal fistula: a case report and review of
      literature.
AB  - Aortoesophageal fistula (AEF) is a rare cause of massive upper gastrointestinal
      hemorrhage. Thoracic aortic aneurysm, esophageal foreign body, esophageal cancer
      and post-surgical complications are common causes of AEF; however, AEF induced by
      radiation therapy is a rare phenomenon and seldom described in the literature. It
      is a catastrophic condition which requires rapid implementation of resuscitative
      measures, broad-spectrum antibiotics and surgical or endovascular intervention.
      Transthoracic endovascular aortic repair (TEVAR) is a newer and less invasive
      technique, which helps to achieve rapid hemostasis in patients with severe
      hemodynamic instability and offers advantages over conventional repair of the
      aorta in emergency situations. However initial TEVAR should be followed up with a
      more definitive surgical repair of the aorta and the esophagus, to lower the
      mortality rate and achieve better outcomes. We describe here a case of a seventy
      year-old male who presented with massive upper gastrointestinal bleeding due to
      AEF induced by radiation therapy, and his subsequent successful initial
      management with TEVAR. 

PMID- 25381205
TI  - Right paraduodenal hernia: report of two cases and review of literature.
AB  - Paraduodenal hernia (PDH), a rare congenital anomaly, is a type of internal
      hernia which occurs due to a defect in the reduction and rotation of the midgut.
      On anatomical and embryological basis, PDH can be broadly divided into right- and
      Left PDH. Right PDH is rarer than its counterpart. We present two cases of Right
      PDH. The patientsy presented with a history of recurrent intestinal obstruction
      since childhood, which was managed conservatively, without a definitive
      diagnosis. Once they presented to us, a detailed clinical history and a barium
      meal follow- through clinched the diagnosis of PDH. Intra-operative findings
      correlated well with the clinical diagnosis. The jejunal loops had herniated
      through the fossa of Waldeyer. Reduction of hernia contents and excision of the
      hernia sac was carried out. Post-operatively, the patients are healthy and
      symptom-free at 4 and 3 years follow-up, respectively. The rarity of this
      condition and the need for early diagnosis, to prevent the high risk of bowel
      obstruction and strangulation, makes PDH one of the difficult challenges for the
      clinicians. 

PMID- 25381203
TI  - Multidisciplinary management of gastrointestinal fibrotic stenosis in Crohn's
      disease.
AB  - Crohn's disease (CD) is a chronic inflammatory bowel disease that can involve
      virtually any part of the gastrointestinal tract. CD complications are the main
      indications for surgery. A large proportion of these interventions are due to
      stricturing disease. Although immunosuppressive treatments have been used more
      frequently during the last 25 years, there is no significant decrease in the need
      for surgery in patients with CD. Unfortunately, surgery is not curative, as the
      disease ultimately reoccurs in a substantial subset of patients. To best identify
      the patients who will require a specific treatment and to plane the most
      appropriate therapeutic approach, it is important to precisely define the type,
      the size, and the location of CD stenosis. Diagnostic approaches aim to
      distinguish fibrotic from inflammatory strictures. Medical therapy is required
      for inflammatory stenosis. Mechanical treatments are required when fibrotic CD
      strictures are symptomatic. The choice between endoscopic balloon dilation,
      stricturoplasty, and laparoscopic or open surgery is based on the presence of
      perforating complications, the remaining length of small bowel, and the number
      and length of strictures. The non-hierarchical decision-making process for the
      treatment of fibrotic CD therefore requires multidisciplinary clinical rounds
      with radiologists, gastroenterologists, interventional endoscopists, and
      surgeons.

PMID- 25381206
TI  - Social Network and Nutritional Value of Congregate Meal Programs: Differences by
      Sexual Orientation.
AB  - This study explored the associations between sexual orientation and the perceived
      social network and nutritional value of congregate meal programs (CMPs) in
      Massachusetts (N = 289). Descriptives, t tests, and chi-square tests analyzed
      sexual orientation differences. Linear regression tested the effects of sexual
      orientation on the value of CMPs. Sexual minorities (SMs) were more likely to
      have non-kin-based social networks and reported higher levels of loneliness
      compared with heterosexuals. Heterosexuals, fewer of whom have non-kin-based
      networks, place a stronger value on access to a social network via CMPs.
      Nutritional value is important for people of all sexual orientations. SMs
      traveled seven times the distance to attend CMPs, highlighting the need for
      greater access to such sites. Results of this study support the specification of
      SMs as a population of "greatest social need" under the Older Americans Act and
      the expansion of services that are tailored for their social support needs.

PMID- 25381208
TI  - Court to decide whether mother committed crime against child with fetal alcohol
      disorder.

PMID- 25381210
TI  - National lung screening trial limitations and public health policy.
AB  - The completion of the National Lung Screening Trial (NLST), a randomized
      controlled trial (RCT) of lung cancer screening (LCS), in 2010 provided powerful
      RCT evidence of the efficacy and safety of computed tomography-based screening;
      nevertheless, the study had important limitations. Failure to understand these
      limitations has had substantial adverse effects. Misinterpretation or
      misrepresentation of the results has led to underestimation of benefits and
      overestimation of adverse effects. When factored into predictive models,
      inaccurate estimates have yielded falsely low projections of potential lives
      saved with national implementation of LCS, exaggerated projected costs, and
      underestimated cost-effectiveness. When extrapolated estimates were presented to
      guideline groups and payer panels by screening critics, results included delay in
      implementation of screening, recommendations to screen only a limited high-risk
      subgroup, and advice to restrict LCS to otherwise undefined "centers of
      excellence" able to enter data into a national registry. Finally, despite the
      formal endorsement of LCS by a large number of prestigious guideline groups,
      inaccurate extrapolation of NLST data has served to convince payer panels to
      recommend against insurance coverage for LCS. This article reviews limitations of
      the NLST study design and compares its results with screening data from many
      other RCTs and clinical programs, with the intention of providing more accurate
      and comprehensive information on the benefits, risks, costs, and cost
      effectiveness of LCS. 

PMID- 25381209
TI  - Shared neurobiological pathways between type 2 diabetes and depressive symptoms:
      a review of morphological and neurocognitive findings.
AB  - Type 2 diabetes (T2D) patients are twice as likely to experience depressive
      symptoms than people without T2D, resulting in greater economic burden, worse
      clinical outcomes, and reduced quality of life. Several overlapping
      pathophysiological processes including hypothalamic-pituitary-adrenal axis
      hyperactivity, sympathetic nervous system activation, and elevated pro
      inflammatory biomarkers are recognized as playing a role between T2D and
      depressive symptoms. However, other neurobiological mechanisms that may help to
      further link these comorbidities have not been extensively reviewed. Reduced
      neuroplasticity in brain regions sensitive to stress (e.g., hippocampus) may be
      associated with T2D and depressive symptoms. T2D patients demonstrate reduced
      neuroplasticity including morphological/volumetric abnormalities and subsequent
      neurocognitive deficits, similar to those reported by patients with depressive
      symptoms. This review aims to summarize recent studies on
      morphological/volumetric abnormalities in T2D and correlated neurocognitive
      deficits. Modifying factors that contribute to reduced neuroplasticity will also
      be discussed. Integrating reduced neuroplasticity with other biological
      correlates of T2D and depressive symptoms could enhance future therapeutic
      interventions and further disentangle the bidirectional associations between
      these comorbidities. 

PMID- 25381211
TI  - The time for low-dose computed tomography screening is now: a medical oncologist
      perspective.

PMID- 25381212
TI  - CT lung cancer screening: public healthcare policy and guidelines collide.

PMID- 25381213
TI  - Lentiform fork sign in a case with end-stage renal disease and metabolic
      acidosis.

PMID- 25381214
TI  - Will hypochondriasis be "alive and well" in the ICD-11?

PMID- 25381215
TI  - Complex care patients within acute care beds.

PMID- 25381216
TI  - Understanding the interplay between motivation and social cognition performance
      in schizophrenia.

PMID- 25381217
TI  - The value proposition of health care for the patient.

PMID- 25381218
TI  - Best articles published in 2014 in Journal of NeuroInterventional Surgery.

PMID- 25381220
TI  - The Normative Orientations of Climate Scientists.
AB  - In 1942 Robert K. Merton tried to demonstrate the structure of the normative
      system of science by specifying the norms that characterized it. The norms were
      assigned the abbreviation CUDOs: Communism, Universalism, Disinterestedness, and
      Organized skepticism. Using the results of an on-line survey of climate
      scientists concerning the norms of science, this paper explores the climate
      scientists' subscription to these norms. The data suggests that while Merton's
      CUDOs remain the overall guiding moral principles, they are not fully endorsed or
      present in the conduct of climate scientists: there is a tendency to withhold
      results until publication, there is the intention of maintaining property rights,
      there is external influence defining research and the tendency to assign the
      significance of authored work according to the status of the author rather than
      content of the paper. These are contrary to the norms of science as proposed by
      Robert K. Merton.

PMID- 25381219
TI  - The single and double blood injection rabbit subarachnoid hemorrhage model.
AB  - Over the past 30 years, the rabbit subarachnoid hemorrhage model (SAH) has been
      used for investigating the post-hemorrhage pathology, especially with respect to
      understanding of the mechanisms of cerebral vasospasm. However, the molecular
      mechanisms of cerebral vasospasm remain to be elucidated. Furthermore, it is not
      clear whether the rabbit SAH model is suitable for the investigation of
      pathological conditions other than cerebral vasospasm, such as early brain
      injury. Therefore, the properties of the rabbit SAH model need to be validated,
      and the reasons for using the rabbit should be clarified. This review explores
      the settings and technical issues of establishing a rabbit cisterna magna single
      and double blood injection SAH model and discusses the characteristics and
      feasibilities of the models.

PMID- 25381221
TI  - miR-629 Targets TRIM33 to Promote TGFbeta/Smad Signaling and Metastatic
      Phenotypes in ccRCC.
AB  - Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and
      clear cell RCC (ccRCC) represents its most common histological subtype. To
      identify a therapeutic target for ccRCC, miRNA expression signatures from ccRCC
      clinical specimens were analyzed. miRNA microarray and real-time PCR analyses
      revealed that miR-629 expression was significantly upregulated in human ccRCC
      compared with adjacent noncancerous renal tissue. Functional inhibition of miR
      629 by a hairpin miRNA inhibitor suppressed ccRCC cell motility and invasion.
      Mechanistically, miR-629 directly targeted tripartite motif-containing 33
      (TRIM33), which inhibits the TGFbeta/Smad signaling pathway. In clinical ccRCC
      specimens, downregulation of TRIM33 was observed with the association of both
      pathologic stages and grades. The miR-629 inhibitor significantly suppressed
      TGFbeta-induced Smad activation by upregulating TRIM33 expression and
      subsequently inhibited the association of Smad2/3 and Smad4. Moreover, a miR-629
      mimic enhanced the effect of TGFbeta on the expression of epithelial-mesenchymal
      transition-related factors as well as on the motility and invasion in ccRCC
      cells. These findings identify miR-629 as a potent regulator of the TGFbeta/Smad
      signaling pathway via TRIM33 in ccRCC. IMPLICATIONS: This study suggests that miR
      629 has biomarker potential through its ability to regulate TGFbeta/Smad
      signaling and accelerate ccRCC cell motility and invasion.

PMID- 25381223
TI  - US cervical cancer prevention efforts are falling short.

PMID- 25381224
TI  - WHO is criticised for political process used when choosing its new Africa
      director.

PMID- 25381222
TI  - Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of
      Endo180 and CD147.
AB  - Epithelial cell-cell contacts maintain normal glandular tissue homeostasis, and
      their breakage can trigger epithelial-to-mesenchymal transition (EMT), a
      fundamental step in the development of metastatic cancer. Despite the ability of
      C-type lectin domains (CTLD) to modulate cell-cell adhesion, it is not known if
      they modulate epithelial adhesion in EMT and tumor progression. Here, the multi
      CTLD mannose receptor, Endo180 (MRC2/uPARAP), was shown using the Kaplan-Meier
      analysis to be predictive of survival outcome in men with early prostate cancer.
      A proteomic screen of novel interaction partners with the fourth CTLD (CTLD4) in
      Endo180 revealed that its complex with CD147 is indispensable for the stability
      of three-dimensional acini formed by nontransformed prostate epithelial cells
      (PEC). Mechanistic study using knockdown of Endo180 or CD147, and treatment with
      an Endo180 mAb targeting CTLD4 (clone 39.10), or a dominant-negative GST-CTLD4
      chimeric protein, induced scattering of PECs associated with internalization of
      Endo180 into endosomes, loss of E-cadherin (CDH1/ECAD), and unzipping of cell
      cell junctions. These findings are the first to demonstrate that a CTLD acts as a
      suppressor and regulatory switch for EMT; thus, positing that stabilization of
      Endo180-CD147 complex is a viable therapeutic strategy to improve rates of
      prostate cancer survival. IMPLICATIONS: This study identifies the interaction
      between CTLD4 in Endo180 and CD147 as an EMT suppressor and indicates that
      stabilization of this molecular complex improves prostate cancer survival rates.

PMID- 25381225
TI  - Developmental Dysplasia of Hip: A Review.

PMID- 25381226
TI  - Barriers and facilitators of pediatric weight management among diverse families.
AB  - OBJECTIVE: To describe barriers and facilitators relevant to pediatric weight
      management from the perspective of at-risk overweight children and families.
      METHODS: Systematic thematic analysis of semistructured interviews with
      overweight children and families from diverse backgrounds at a large, urban
      academic pediatrics practice. RESULTS: Twenty-five parents and their children
      ages 2 to 18 years with mean body mass index percentile of 96th% (standard
      deviation 4.3) participated. Fifty-six percent were Black; 40% were
      Hispanic/Other race. Perceived barriers to successful weight management included
      (a) inadequate resources (financial, time, access to programming, knowledge), (b)
      challenging social contexts (cultural practices and expectations, interpersonal
      dynamics), (c) negative emotional state (lack of confidence, defeat, loneliness),
      and (d) denial. Participants described linkages to resources, child-parent-
      provider partnerships, and consistent support as key elements in successful
      weight management. Participants also endorsed technology use for weight
      management support. CONCLUSIONS: Multiple barriers and facilitators affect weight
      management among at-risk families, which should be considered in future obesity
      interventions.

PMID- 25381227
TI  - Use of an After-Visit Summary to Augment Mental Health of Children and
      Adolescents.

PMID- 25381228
TI  - Fulminant Liver Failure Presenting Shortly After Initiation of Doxycycline: A
      Case Report.

PMID- 25381229
TI  - Is primary Sjogren's syndrome an orphan disease? A critical appraisal of
      prevalence studies in Europe.

PMID- 25381230
TI  - Venous thromboembolic events in systemic vasculitis.

PMID- 25381231
TI  - PPAD is not targeted as a citrullinated protein in rheumatoid arthritis, but
      remains a candidate for inducing autoimmunity.

PMID- 25381232
TI  - Transcriptomics-aided dissection of the intracellular and extracellular roles of
      microcystin in Microcystis aeruginosa PCC 7806.
AB  - Recent studies have provided evidence for both intracellular and extracellular
      roles of the potent hepatotoxin microcystin (MC) in the bloom-forming
      cyanobacterium Microcystis. Here, we surveyed transcriptomes of the wild-type
      strain M. aeruginosa PCC 7806 and the microcystin-deficient DeltamcyB mutant
      under low light conditions with and without the addition of external MC of the LR
      variant (MC-LR). Transcriptomic data acquired by microarray and quantitative PCR
      revealed substantial differences in the relative expression of genes of the
      central intermediary metabolism, photosynthesis, and energy metabolism. In
      particular, the data provide evidence for a lower photosystem I (PSI)-to
      photosystem II (PSII) ratio and a more pronounced carbon limitation in the
      microcystin-deficient mutant. Interestingly, only 6% of the transcriptional
      differences could be complemented by external microcystin-LR addition. This MC
      signaling effect was seen exclusively for genes of the secondary metabolism
      category. The orphan polyketide synthase gene cluster IPF38-51 was specifically
      downregulated in response to external MC-LR under low light. Our data suggest a
      hierarchical and light-dependent cross talk of secondary metabolites and support
      both an intracellular and an extracellular role of MC in Microcystis. 

PMID- 25381233
TI  - Aerosolization of respirable droplets from a domestic spa pool and the use of MS
      2 coliphage and Pseudomonas aeruginosa as markers for Legionella pneumophila.
AB  - Legionnaires' disease can result when droplets or aerosols containing legionella
      bacteria are inhaled and deposited in the lungs. A number of outbreaks have been
      associated with the use of a spa pool where aeration, a high water temperature,
      and a large and variable organic load make disinfectant levels difficult to
      maintain. Spa pool ownership is increasing, and the aim of this study, using two
      surrogate organisms (MS-2 coliphage and Pseudomonas aeruginosa [a natural
      contaminant]), was to assess the potential risk to domestic users when
      disinfection fails. A representative "entry level" domestic spa pool was
      installed in an outdoor courtyard. The manufacturer's instructions for spa pool
      maintenance were not followed. A cyclone sampler was used to sample the aerosols
      released from the spa pool with and without activation of the air injection
      system. Samples were taken at increasing heights and distances from the pool. An
      aerodynamic particle sizer was used to measure the water droplet size
      distribution at each sample point. When the air injection system was inactivated,
      neither surrogate organism was recovered from the air. On activation of the air
      injection system, the mean mass of droplets within the respirable range (10 cm
      above the water line) was 36.8 MUg cm(-3). This corresponded to a mean air
      concentration of P. aeruginosa of 350 CFU m(-3). From extrapolation from animal
      data, the estimated risk of infection from aerosols contaminated with similar
      concentrations of Legionella pneumophila was 0.76 (males) and 0.65 (females). At
      1 m above and/or beyond the pool, the mean aerosol mass decreased to 0.04 MUg cm(
      3) and corresponded to a 100-fold reduction in mean microbial air concentration.
      The estimated risk of infection at this distance was negligible. 

PMID- 25381234
TI  - Genomic diversity and virulence profiles of historical Escherichia coli O157
      strains isolated from clinical and environmental sources.
AB  - Escherichia coli O157:H7 is, to date, the major E. coli serotype causing food
      borne human disease worldwide. Strains of O157 with other H antigens also have
      been recovered. We analyzed a collection of historic O157 strains (n = 400)
      isolated in the late 1980s to early 1990s in the United States. Strains were
      predominantly serotype O157:H7 (55%), and various O157:non-H7 (41%) serotypes
      were not previously reported regarding their pathogenic potential. Although
      lacking Shiga toxin (stx) and eae genes, serotypes O157:H1, O157:H2, O157:H11,
      O157:H42, and O157:H43 carried several virulence factors (iha, terD, and hlyA)
      also found in virulent serotype E. coli O157:H7. Pulsed-field gel electrophoresis
      (PFGE) showed the O157 serogroup was diverse, with strains with the same H type
      clustering together closely. Among non-H7 isolates, serotype O157:H43 was highly
      prevalent (65%) and carried important enterohemorrhagic E. coli (EHEC) virulence
      markers (iha, terD, hlyA, and espP). Isolates from two particular H types, H2 and
      H11, among the most commonly found non-O157 EHEC serotypes (O26:H11, O111:H11,
      O103:H2/H11, and O45:H2), unexpectedly clustered more closely with O157:H7 than
      other H types and carried several virulence genes. This suggests an early
      divergence of the O157 serogroup to clades with different pathogenic potentials.
      The appearance of important EHEC virulence markers in closely related H types
      suggests their virulence potential and suggests further monitoring of those
      serotypes not implicated in severe illness thus far. 

PMID- 25381235
TI  - Modeling the recovery of heat-treated Bacillus licheniformis Ad978 and Bacillus
      weihenstephanensis KBAB4 spores at suboptimal temperature and pH using growth
      limits.
AB  - The apparent heat resistance of spores of Bacillus weihenstephanensis and
      Bacillus licheniformis was measured and expressed as the time to first decimal
      reduction (delta value) at a given recovery temperature and pH. Spores of B.
      weihenstephanensis were produced at 30 degrees C and 12 degrees C, and spores of
      B. licheniformis were produced at 45 degrees C and 20 degrees C. B.
      weihenstephanensis spores were then heat treated at 85 degrees C, 90 degrees C,
      and 95 degrees C, and B. licheniformis spores were heat treated at 95 degrees C,
      100 degrees C, and 105 degrees C. Heat-treated spores were grown on nutrient agar
      at a range of temperatures (4 degrees C to 40 degrees C for B. weihenstephanensis
      and 15 degrees C to 60 degrees C for B. licheniformis) or a range of pHs (between
      pH 4.5 and pH 9.5 for both strains). The recovery temperature had a slight effect
      on the apparent heat resistance, except very near recovery boundaries. In
      contrast, a decrease in the recovery pH had a progressive impact on apparent heat
      resistance. A model describing the heat resistance and the ability to recover
      according to the sporulation temperature, temperature of treatment, and recovery
      temperature and pH was proposed. This model derived from secondary mathematical
      models for growth prediction. Previously published cardinal temperature and pH
      values were used as input parameters. The fitting of the model with apparent heat
      resistance data obtained for a wide range of spore treatment and recovery
      conditions was highly satisfactory. 

PMID- 25381236
TI  - Dehalococcoides mccartyi strain DCMB5 Respires a broad spectrum of chlorinated
      aromatic compounds.
AB  - Polyhalogenated aromatic compounds are harmful environmental contaminants and
      tend to persist in anoxic soils and sediments. Dehalococcoides mccartyi strain
      DCMB5, a strain originating from dioxin-polluted river sediment, was examined for
      its capacity to dehalogenate diverse chloroaromatic compounds. Strain DCMB5 used
      hexachlorobenzenes, pentachlorobenzenes, all three tetrachlorobenzenes, and 1,2,3
      trichlorobenzene as well as 1,2,3,4-tetra- and 1,2,4-trichlorodibenzo-p-dioxin as
      electron acceptors for organohalide respiration. In addition, 1,2,3
      trichlorodibenzo-p-dioxin and 1,3-, 1,2-, and 1,4-dichlorodibenzo-p-dioxin were
      dechlorinated, the latter to the nonchlorinated congener with a remarkably short
      lag phase of 1 to 4 days following transfer. Strain DCMB5 also dechlorinated
      pentachlorophenol and almost all tetra- and trichlorophenols. Tetrachloroethene
      was dechlorinated to trichloroethene and served as an electron acceptor for
      growth. To relate selected dechlorination activities to the expression of
      specific reductive dehalogenase genes, the proteomes of 1,2,3-trichlorobenzene-,
      pentachlorobenzene-, and tetrachloroethene-dechlorinating cultures were analyzed.
      Dcmb_86, an ortholog of the chlorobenzene reductive dehalogenase CbrA, was the
      most abundant reductive dehalogenase during growth with each electron acceptor,
      suggesting its pivotal role in organohalide respiration of strain DCMB5.
      Dcmb_1041 was specifically induced, however, by both chlorobenzenes, whereas 3
      putative reductive dehalogenases, Dcmb_1434, Dcmb_1339, and Dcmb_1383, were
      detected only in tetrachloroethene-grown cells. The proteomes also harbored a
      type IV pilus protein and the components for its assembly, disassembly, and
      secretion. In addition, transmission electron microscopy of DCMB5 revealed an
      irregular mode of cell division as well as the presence of pili, indicating that
      pilus formation is a feature of D. mccartyi during organohalide respiration. 

PMID- 25381237
TI  - Glutamate decarboxylase-dependent acid resistance in Brucella spp.: distribution
      and contribution to fitness under extremely acidic conditions.
AB  - Brucella is an expanding genus of major zoonotic pathogens, including at least 10
      genetically very close species occupying a wide range of niches from soil to
      wildlife, livestock, and humans. Recently, we have shown that in the new species
      Brucella microti, the glutamate decarboxylase (Gad)-dependent system (GAD system)
      contributes to survival at a pH of 2.5 and also to infection in mice by the oral
      route. In order to study the functionality of the GAD system in the genus
      Brucella, 47 isolates, representative of all known species and strains of this
      genus, and 16 strains of the closest neighbor genus, Ochrobactrum, were studied
      using microbiological, biochemical, and genetic approaches. In agreement with the
      genome sequences, the GAD system of classical species was not functional, unlike
      that of most strains of Brucella ceti, Brucella pinnipedialis, and newly
      described species (B. microti, Brucella inopinata BO1, B. inopinata-like BO2, and
      Brucella sp. isolated from bullfrogs). In the presence of glutamate, these
      species were more acid resistant in vitro than classical terrestrial brucellae.
      Expression in trans of the gad locus from representative Brucella species in the
      Escherichia coli MG1655 mutant strain lacking the GAD system restored the acid
      resistant phenotype. The highly conserved GAD system of the newly described or
      atypical Brucella species may play an important role in their adaptation to
      acidic external and host environments. Furthermore, the GAD phenotype was shown
      to be a useful diagnostic tool to distinguish these latter Brucella strains from
      Ochrobactrum and from classical terrestrial pathogenic Brucella species, which
      are GAD negative. 

PMID- 25381238
TI  - Engineering Neurospora crassa for improved cellobiose and cellobionate
      production.
AB  - We report engineering Neurospora crassa to improve the yield of cellobiose and
      cellobionate from cellulose. A previously engineered strain of N. crassa (F5)
      with six of seven beta-glucosidase (bgl) genes knocked out was shown to produce
      cellobiose and cellobionate directly from cellulose without the addition of
      exogenous cellulases. In this study, the F5 strain was further modified to
      improve the yield of cellobiose and cellobionate from cellulose by increasing
      cellulase production and decreasing product consumption. The effects of two
      catabolite repression genes, cre-1 and ace-1, on cellulase production were
      investigated. The F5 Deltaace-1 mutant showed no improvement over the wild type.
      The F5 Deltacre-1 and F5 Deltaace-1 Deltacre-1 strains showed improved cellobiose
      dehydrogenase and exoglucanase expression. However, this improvement in cellulase
      expression did not lead to an improvement in cellobiose or cellobionate
      production. The cellobionate phosphorylase gene (ndvB) was deleted from the
      genome of F5 Deltaace-1 Deltacre-1 to prevent the consumption of cellobiose and
      cellobionate. Despite a slightly reduced hydrolysis rate, the F5 Deltaace-1
      Deltacre-1 DeltandvB strain converted 75% of the cellulose consumed to the
      desired products, cellobiose and cellobionate, compared to 18% converted by the
      strain F5 Deltaace-1 Deltacre-1. 

PMID- 25381239
TI  - Synthesis and succinylation of subtilin-like lantibiotics are strongly influenced
      by glucose and transition state regulator AbrB.
AB  - Subtilin and the closely related entianin are class I lantibiotics produced by
      different subspecies of Bacillus subtilis. Both molecules are ribosomally
      synthesized peptide antibiotics with unusual ring structures. Subtilin-like
      lantibiotics develop strong antibiotic activities against various Gram-positive
      organisms with an efficiency similar to that of nisin from Lactococcus lactis. In
      contrast to nisin, subtilin-like lantibiotics partially undergo an additional
      posttranslational modification, where the N-terminal tryptophan residue becomes
      succinylated, resulting in drastically reduced antibiotic activities. A highly
      sensitive high-performance liquid chromatography (HPLC)-based quantification
      method enabled us to determine entianin and succinylated entianin (S-entianin)
      concentrations in the supernatant during growth. We show that entianin synthesis
      and the degree of succinylation drastically change with culture conditions. In
      particular, increasing glucose concentrations resulted in higher entianin amounts
      and lower proportions of S-entianin in Landy-based media. In contrast, no
      succinylation was observed in medium A with 10% glucose. Interestingly, glucose
      retarded the expression of entianin biosynthesis genes. Furthermore, deletion of
      the transition state regulator AbrB resulted in a 6-fold increased entianin
      production in medium A with 10% glucose. This shows that entianin biosynthesis in
      B. subtilis is strongly influenced by glucose, in addition to its regulation by
      the transition state regulator AbrB. Our results suggest that the mechanism
      underlying the succinylation of subtilin-like lantibiotics is enzymatically
      catalyzed and occurs in the extracellular space or at the cellular membrane. 

PMID- 25381241
TI  - Pyrosequencing of mcrA and archaeal 16S rRNA genes reveals diversity and
      substrate preferences of methanogen communities in anaerobic digesters.
AB  - Methanogenic archaea play a key role in biogas-producing anaerobic digestion and
      yet remain poorly taxonomically characterized. This is in part due to the
      limitations of low-throughput Sanger sequencing of a single (16S rRNA) gene,
      which in the past may have undersampled methanogen diversity. In this study,
      archaeal communities from three sludge digesters in Hong Kong and one wastewater
      digester in China were examined using high-throughput pyrosequencing of the
      methyl coenzyme M reductase (mcrA) and 16S rRNA genes. Methanobacteriales,
      Methanomicrobiales, and Methanosarcinales were detected in each digester,
      indicating that both hydrogenotrophic and acetoclastic methanogenesis was
      occurring. Two sludge digesters had similar community structures, likely due to
      their similar design and feedstock. Taxonomic classification of the mcrA genes
      suggested that these digesters were dominated by acetoclastic methanogens,
      particularly Methanosarcinales, while the other digesters were dominated by
      hydrogenotrophic Methanomicrobiales. The proposed euryarchaeotal order
      Methanomassiliicoccales and the uncultured WSA2 group were detected with the 16S
      rRNA gene, and potential mcrA genes for these groups were identified. 16S rRNA
      gene sequencing also recovered several crenarchaeotal groups potentially involved
      in the initial anaerobic digestion processes. Overall, the two genes produced
      different taxonomic profiles for the digesters, while greater methanogen richness
      was detected using the mcrA gene, supporting the use of this functional gene as a
      complement to the 16S rRNA gene to better assess methanogen diversity. A
      significant positive correlation was detected between methane production and the
      abundance of mcrA transcripts in digesters treating sludge and wastewater
      samples, supporting the mcrA gene as a biomarker for methane yield. 

PMID- 25381240
TI  - Bartonella chomelii is the most frequent species infecting cattle grazing in
      communal mountain pastures in Spain.
AB  - The presence of Bartonella spp. was investigated in domestic ungulates grazing in
      communal pastures from a mountain area in northern Spain, where 18.3% (17/93) of
      cattle were found to be positive by PCR combined with a reverse line blot
      (PCR/RLB), whereas sheep (n = 133) or horses (n = 91) were found not to be
      infected by this pathogen. Bartonella infection was significantly associated with
      age, since older animals showed a higher prevalence than heifers and calves. In
      contrast to other studies, B. chomelii was the most frequent species found in
      cattle (14/17), while B. bovis was detected in only three animals. Moreover, 18
      B. chomelii isolates and one B. bovis isolate were obtained from nine animals.
      Afterwards, B. chomelii isolates were characterized by a multilocus sequence
      typing (MLST) method which was adapted in this study. This method presented a
      high discrimination power, identifying nine different sequence types (STs). This
      characterization also showed the presence of different STs simultaneously in the
      same host and that STs had switched over time in one of the animals. In addition,
      B. chomelii STs seem to group phylogenetically in two different lineages. The
      only B. bovis isolate was characterized with a previously described MLST method.
      This isolate corresponded to a new ST which is located in lineage I, where the B.
      bovis strains infecting Bos taurus subsp. taurus are grouped. Further studies on
      the dynamics of Bartonella infection in cattle and the potential ectoparasites
      involved in the transmission of this microorganism should be performed, improving
      knowledge about the interaction of Bartonella spp. and domestic ungulates. 

PMID- 25381242
TI  - Exposure to synthetic gray water inhibits amoeba encystation and alters
      expression of Legionella pneumophila virulence genes.
AB  - Water conservation efforts have focused on gray water (GW) usage, especially for
      applications that do not require potable water quality. However, there is a need
      to better understand environmental pathogens and their free-living amoeba (FLA)
      hosts within GW, given their growth potential in stored gray water. Using
      synthetic gray water (sGW) we examined three strains of the water-based pathogen
      Legionella pneumophila and its FLA hosts Acanthamoeba polyphaga, A. castellanii,
      and Vermamoeba vermiformis. Exposure to sGW for 72 h resulted in significant
      inhibition (P < 0.0001) of amoebal encystation versus control-treated cells, with
      the following percentages of cysts in sGW versus controls: A. polyphaga (0.6
      versus 6%), A. castellanii (2 versus 62%), and V. vermiformis (1 versus 92%),
      suggesting sGW induced maintenance of the actively feeding trophozoite form.
      During sGW exposure, L. pneumophila culturability decreased as early as 5 h (1.3
      to 2.9 log10 CFU, P < 0.001) compared to controls (Delta0 to 0.1 log10 CFU) with
      flow cytometric analysis revealing immediate changes in membrane permeability.
      Furthermore, reverse transcription-quantitative PCR was performed on total RNA
      isolated from L. pneumophila cells at 0 to 48 h after sGW incubation, and genes
      associated with virulence (gacA, lirR, csrA, pla, and sidF), the type IV
      secretion system (lvrB and lvrE), and metabolism (ccmF and lolA) were all shown
      to be differentially expressed. These results suggest that conditions within GW
      may promote interactions between water-based pathogens and FLA hosts, through
      amoebal encystment inhibition and alteration of bacterial gene expression, thus
      warranting further exploration into FLA and L. pneumophila behavior in GW
      systems. 

PMID- 25381243
TI  - Entericidin is required for a probiotic treatment (Enterobacter sp. strain C6-6)
      to protect trout from cold-water disease challenge.
AB  - Flavobacterium psychrophilum causes bacterial cold-water disease in multiple fish
      species, including salmonids. An autochthonous Enterobacter strain (C6-6)
      inhibits the in vitro growth of F. psychrophilum, and when ingested as a putative
      probiotic, it provides protection against injection challenge with F.
      psychrophilum in rainbow trout. In this study, low-molecular-mass (<=3 kDa)
      fractions from both Enterobacter C6-6 and Escherichia coli K-12 culture
      supernatants inhibited the growth of F. psychrophilum. The <=3-kDa fraction from
      Enterobacter C6-6 was analyzed by SDS-PAGE, and subsequent tandem mass
      spectroscopy identified EcnB, which is a small membrane lipoprotein that is a
      putative pore-forming toxin. Agar plate diffusion assays demonstrated that ecnAB
      knockout strains of both Enterobacter C6-6 and E. coli K-12 no longer inhibited
      F. psychrophilum (P < 0.001), while ecnAB-complemented knockout strains recovered
      the inhibitory phenotype (P < 0.001). In fish experiments, the engineered strains
      (C6-6 DeltaecnAB and C6-6 DeltaecnAB<pET101::ecnAB>) and the wild-type strain (C6
      6) were added to the fish diet every day for 38 days. On day 11, the fish were
      challenged by injection with a virulent strain of F. psychrophilum (CSF 259-93).
      Fish that were fed C6-6 had significantly longer survival than fish fed the ecnAB
      knockout strain (P < 0.0001), while fish fed the complemented knockout strain
      recovered the probiotic phenotype (P = 0.61). This entericidin is responsible for
      the probiotic activity of Enterobacter C6-6, and it may present new opportunities
      for therapeutic and prophylactic treatments against similarly susceptible
      pathogens. 

PMID- 25381246
TI  - Cardiovascular disease in Europe 2014: epidemiological update.

PMID- 25381245
TI  - Plasmid-mediated resistance to cephalosporins and fluoroquinolones in various
      Escherichia coli sequence types isolated from rooks wintering in Europe.
AB  - Extended-spectrum-beta-lactamase (ESBL)-producing, AmpC beta-lactamase-producing,
      and plasmid-mediated quinolone resistance (PMQR) gene-positive strains of
      Escherichia coli were investigated in wintering rooks (Corvus frugilegus) from
      eight European countries. Fecal samples (n = 1,073) from rooks wintering in the
      Czech Republic, France, Germany, Italy, Poland, Serbia, Spain, and Switzerland
      were examined. Resistant isolates obtained from selective cultivation were
      screened for ESBL, AmpC, and PMQR genes by PCR and sequencing. Pulsed-field gel
      electrophoresis and multilocus sequence typing were performed to reveal their
      clonal relatedness. In total, from the 1,073 samples, 152 (14%) cefotaxime
      resistant E. coli isolates and 355 (33%) E. coli isolates with reduced
      susceptibility to ciprofloxacin were found. Eighty-two (54%) of these cefotaxime
      resistant E. coli isolates carried the following ESBL genes: blaCTX-M-1 (n = 39
      isolates), blaCTX-M-15 (n = 25), blaCTX-M-24 (n = 4), blaTEM-52 (n = 4), blaCTX-M
      14 (n = 2), blaCTX-M-55 (n = 2), blaSHV-12 (n = 2), blaCTX-M-8 (n = 1), blaCTX-M
      25 (n = 1), blaCTX-M-28 (n = 1), and an unspecified gene (n = 1). Forty-seven
      (31%) cefotaxime-resistant E. coli isolates carried the blaCMY-2 AmpC beta
      lactamase gene. Sixty-two (17%) of the E. coli isolates with reduced
      susceptibility to ciprofloxacin were positive for the PMQR genes qnrS1 (n = 54),
      qnrB19 (n = 4), qnrS1 and qnrB19 (n = 2), qnrS2 (n = 1), and aac(6')-Ib-cr (n =
      1). Eleven isolates from the Czech Republic (n = 8) and Serbia (n = 3) were
      identified to be CTX-M-15-producing E. coli clone B2-O25b-ST131 isolates. Ninety
      one different sequence types (STs) among 191 ESBL-producing, AmpC-producing, and
      PMQR gene-positive E. coli isolates were determined, with ST58 (n = 15), ST10 (n
      = 14), and ST131 (n = 12) predominating. The widespread occurrence of highly
      diverse ESBL- and AmpC-producing and PMQR gene-positive E. coli isolates,
      including the clinically important multiresistant ST69, ST95, ST117, ST131, and
      ST405 clones, was demonstrated in rooks wintering in various European countries. 

PMID- 25381244
TI  - Application of chitosan microparticles for reduction of vibrio species in
      seawater and live oysters (Crassostrea virginica).
AB  - Human Vibrio infections associated with consumption of raw shellfish greatly
      impact the seafood industry. Vibrio cholerae-related disease is occasionally
      attributed to seafood, but V. vulnificus and V. parahaemolyticus are the primary
      targets of postharvest processing (PHP) efforts in the United States, as they
      pose the greatest threat to the industry. Most successful PHP treatments for
      Vibrio reduction also kill the molluscs and are not suitable for the lucrative
      half-shell market, while nonlethal practices are generally less effective.
      Therefore, novel intervention strategies for Vibrio reduction are needed for live
      oyster products. Chitosan is a bioactive derivative of chitin that is generally
      recognized as safe as a food additive by the FDA, and chitosan microparticles
      (CMs) were investigated in the present study as a potential PHP treatment for
      live oyster applications. Treatment of broth cultures with 0.5% (wt/vol) CMs
      resulted in growth cessation of V. cholerae, V. vulnificus, and V.
      parahaemolyticus, reducing culturable levels to nondetectable amounts after 3 h
      in three independent experiments. Furthermore, a similar treatment in artificial
      seawater at 4, 25, and 37 degrees C reduced V. vulnificus levels by ca. 7 log
      CFU/ml after 24 h of exposure, but 48 h of exposure and elevated temperature were
      required to achieve similar results for V. parahaemolyticus and V. cholerae. Live
      oysters that either were artificially inoculated or contained natural populations
      of V. vulnificus and V. parahaemolyticus showed significant and consistent
      reductions following CM treatment (5%) compared to the amounts in the untreated
      controls. Thus, the results strongly support the promising potential for the
      application of CMs as a PHP treatment to reduce Vibrio spp. in intact live
      oysters. 

PMID- 25381247
TI  - Microseconds simulations reveal a new sodium-binding site and the mechanism of
      sodium-coupled substrate uptake by LeuT.
AB  - The bacterial sodium-coupled leucine/alanine transporter LeuT is broadly used as
      a model system for studying the transport mechanism of neurotransmitters because
      of its structural and functional homology to mammalian transporters such as
      serotonin, dopamine, or norepinephrine transporters, and because of the
      resolution of its structure in different states. Although the binding sites (S1
      for substrate, and Na1 and Na2 for two co-transported sodium ions) have been
      resolved, we still lack a mechanistic understanding of coupled Na(+)- and
      substrate-binding events. We present here results from extensive (>20 MUs)
      unbiased molecular dynamics simulations generated using the latest computing
      technology. Simulations show that sodium binds initially the Na1 site, but not
      Na2, and, consistently, sodium unbinding/escape to the extracellular (EC) region
      first takes place at Na2, succeeded by Na1. Na2 diffusion back to the EC medium
      requires prior dissociation of substrate from S1. Significantly, Na(+) binding
      (and unbinding) consistently involves a transient binding to a newly discovered
      site, Na1", near S1, as an intermediate state. A robust sequence of substrate
      uptake events coupled to sodium bindings and translocations between those sites
      assisted by hydration emerges from the simulations: (i) bindings of a first Na(+)
      to Na1", translocation to Na1, a second Na(+) to vacated Na1" and then to Na2,
      and substrate to S1; (ii) rotation of Phe(253) aromatic group to seclude the
      substrate from the EC region; and (iii) concerted tilting of TM1b and TM6a toward
      TM3 and TM8 to close the EC vestibule. 

PMID- 25381248
TI  - Spectrin tetramer formation is not required for viable development in Drosophila.
AB  - The dominant paradigm for spectrin function is that (alphabeta)2-spectrin
      tetramers or higher order oligomers form membrane-associated two-dimensional
      networks in association with F-actin to reinforce the plasma membrane.
      Tetramerization is an essential event in such structures. We characterize the
      tetramerization interaction between alpha-spectrin and beta-spectrins in
      Drosophila. Wild-type alpha-spectrin binds to both beta- and betaH-chains with
      high affinity, resembling other non-erythroid spectrins. However, alpha
      spec(R22S), a tetramerization site mutant homologous to the pathological alpha
      spec(R28S) allele in humans, eliminates detectable binding to beta-spectrin and
      reduces binding to betaH-spectrin ~1000-fold. Even though spectrins are essential
      proteins, alpha-spectrin(R22S) rescues alpha-spectrin mutants to adulthood with
      only minor phenotypes indicating that tetramerization, and thus conventional
      network formation, is not the essential function of non-erythroid spectrin. Our
      data provide the first rigorous test for the general requirement for tetramer
      based non-erythroid spectrin networks throughout an organism and find that they
      have very limited roles, in direct contrast to the current paradigm. 

PMID- 25381249
TI  - Inhibition of arginyltransferase 1 induces transcriptional activity of myocardin
      related transcription factor A (MRTF-A) and promotes directional migration.
AB  - Myocardin-related transcription factor A (MRTF-A/MAL/MKL1/BSAC) regulates the
      expression of serum-response factor (SRF)-dependent target genes in response to
      the Rho-actin signaling pathway. Overexpression or activation of MRTF-A affects
      shape, migration, and invasion of cells and contributes to human malignancies,
      including cancer. In this study, we report that inhibition of arginyltransferase
      1 (ATE1), an enzyme mediating post-transcriptional protein arginylation, is
      sufficient to increase MRTF-A activity in MCF-7 human breast carcinoma cells
      independently of external growth factor stimuli. In addition, silencing or
      inhibiting ATE1 disrupted E-cadherin-mediated cell-cell contacts, enhanced
      formation of actin-rich protrusions, and increased the number of focal adhesions,
      subsequently leading to elevated chemotactic migration. Although arginylated
      actin did not differentially affect MRTF-A, a rapid loss of E-cadherin and F
      actin reorganization preceded MRTF-A activation upon ATE1 inhibition. Conversely,
      ectopic ATE1 expression was sufficient to render MRTF-A inactive, both in resting
      cells and in cells with exogenously activated RhoA-actin pathways. In this study,
      we provide a critical link between protein arginylation and MRTF-A activity and
      place ATE1 upstream of myocardin-related transcription factor. 

PMID- 25381250
TI  - Adaptor protein GRB2 promotes Src tyrosine kinase activation and podosomal
      organization by protein-tyrosine phosphatase epsilon in osteoclasts.
AB  - The non-receptor isoform of protein-tyrosine phosphatase epsilon (cyt-PTPe)
      supports adhesion of bone-resorbing osteoclasts by activating Src downstream of
      integrins. Loss of cyt-PTPe reduces Src activity in osteoclasts, reduces
      resorption of mineralized matrix both in vivo and in cell culture, and induces
      mild osteopetrosis in young female PTPe KO mice. Activation of Src by cyt-PTPe is
      dependent upon this phosphatase undergoing phosphorylation at its C-terminal Tyr
      638 by partially active Src. To understand how cyt-PTPe activates Src, we
      screened 73 Src homology 2 (SH2) domains for binding to Tyr(P)-638 of cyt-PTPe.
      The SH2 domain of GRB2 bound Tyr(P)-638 of cyt-PTPe most prominently, whereas the
      Src SH2 domain did not bind at all, suggesting that GRB2 may link PTPe with
      downstream molecules. Further studies indicated that GRB2 is required for
      activation of Src by cyt-PTPe in osteoclast-like cells (OCLs) in culture.
      Overexpression of GRB2 in OCLs increased activating phosphorylation of Src at Tyr
      416 and of cyt-PTPe at Tyr-638; opposite results were obtained when GRB2
      expression was reduced by shRNA or by gene inactivation. Phosphorylation of cyt
      PTPe at Tyr-683 and its association with GRB2 are integrin-driven processes in
      OCLs, and cyt-PTPe undergoes autodephosphorylation at Tyr-683, thus limiting Src
      activation by integrins. Reduced GRB2 expression also reduced the ability of bone
      marrow precursors to differentiate into OCLs and reduced the fraction of OCLs in
      which podosomal adhesion structures assume organization typical of active,
      resorbing cells. We conclude that GRB2 physically links cyt-PTPe with Src and
      enables cyt-PTPe to activate Src downstream of activated integrins in OCLs. 

PMID- 25381251
TI  - Agonist-promoted ubiquitination differentially regulates receptor trafficking of
      endothelin type A and type B receptors.
AB  - Two types of G protein-coupled receptors for endothelin-1 (ET-1), ET type A
      receptor (ETAR) and ETBR, closely resemble each other, but upon ET-1 stimulation,
      they follow totally different intracellular trafficking pathways; ETAR is
      recycled back to plasma membrane, whereas ETBR is targeted to lysosome for
      degradation. However, the mechanisms for such different fates are unknown. Here
      we demonstrated that ETBR but not ETAR was ubiquitinated on the cell surface
      following ET-1 stimulation and that ETBR was internalized and degraded in
      lysosome more rapidly than ETAR. The mutant ETBR (designated "5KR mutant") in
      which 5 lysine residues in the C-tail were substituted to arginine was not
      ubiquitinated, and its rates of internalization and degradation after ET-1
      stimulation became slower, being comparable with those of ETAR. Confocal
      microscopic study showed that following ET-1 stimulation, ETAR and 5KR mutant of
      ETBR were co-localized mainly with Rab11, a marker of recycling endosome, whereas
      ETBR was co-localized with Rab7, a marker of late endosome/lysosome. In the 5KR
      mutant, ET-1-induced ERK phosphorylation and an increase in the intracellular
      Ca(2+) concentration upon repetitive ET-1 stimulation were larger. A series of
      ETBR mutants (designated "4KR mutant"), in which either one of 5 arginine
      residues of the 5KR mutant was reverted to lysine, were normally ubiquitinated,
      internalized, and degraded, with ERK phosphorylation being normalized. These
      results demonstrate that agonist-induced ubiquitination at either lysine residue
      in the C-tail of ETBR but not ETAR switches intracellular trafficking from
      recycling to plasma membrane to targeting to lysosome, causing decreases in the
      cell surface level of ETBR and intracellular signaling. 

PMID- 25381254
TI  - Versatility of homogeneous time-resolved fluorescence resonance energy transfer
      assays for biologics drug discovery.
AB  - Identification of potential lead antibodies in the drug discovery process
      requires the use of assays that not only measure binding of the antibody to the
      target molecule but assess a wide range of other characteristics. These include
      affinity ranking, measurement of their ability to inhibit relevant protein
      protein interactions, assessment of their selectivity for the target protein, and
      determination of their species cross-reactivity profiles to support in vivo
      studies. Time-resolved fluorescence resonance energy transfer is a technology
      that offers the flexibility for development of such assays, through the
      availability of donor and acceptor fluorophore-conjugated reagents for detection
      of multiple tags or fusion proteins. The time-resolved component of the
      technology reduces potential assay interference, allowing screening of a range of
      different crude sample types derived from the bacterial or mammalian cell
      expression systems often used for antibody discovery projects. Here we describe
      the successful application of this technology across multiple projects targeting
      soluble proteins and demonstrate how it has provided key information for the
      isolation of potential therapeutic antibodies with the desired activity profile. 

PMID- 25381252
TI  - The hepatitis C virus core protein inhibits adipose triglyceride lipase (ATGL)
      mediated lipid mobilization and enhances the ATGL interaction with comparative
      gene identification 58 (CGI-58) and lipid droplets.
AB  - Liver steatosis is a common health problem associated with hepatitis C virus
      (HCV) and an important risk factor for the development of liver fibrosis and
      cancer. Steatosis is caused by triglycerides (TG) accumulating in lipid droplets
      (LDs), cellular organelles composed of neutral lipids surrounded by a monolayer
      of phospholipids. The HCV nucleocapsid core localizes to the surface of LDs and
      induces steatosis in cultured cells and mouse livers by decreasing intracellular
      TG degradation (lipolysis). Here we report that core at the surface of LDs
      interferes with the activity of adipose triglyceride lipase (ATGL), the key
      lipolytic enzyme in the first step of TG breakdown. Expressing core in livers or
      mouse embryonic fibroblasts of ATGL(-/-) mice no longer decreases TG degradation
      as observed in LDs from wild-type mice, supporting the model that core reduces
      lipolysis by engaging ATGL. Core must localize at LDs to inhibit lipolysis, as ex
      vivo TG hydrolysis is impaired in purified LDs coated with core but not when free
      core is added to LDs. Coimmunoprecipitation experiments revealed that core does
      not directly interact with the ATGL complex but, unexpectedly, increased the
      interaction between ATGL and its activator CGI-58 as well as the recruitment of
      both proteins to LDs. These data link the anti-lipolytic activity of the HCV core
      protein with altered ATGL binding to CGI-58 and the enhanced association of both
      proteins with LDs. 

PMID- 25381253
TI  - A high-throughput phenotypic screen of cytotoxic T lymphocyte lytic granule
      exocytosis reveals candidate immunosuppressants.
AB  - We screened the National Institutes of Health's Molecular Libraries Small
      Molecule Repository for inhibitors of cytotoxic T lymphocyte (CTL) lytic granule
      exocytosis by measuring binding of an antibody in the extracellular solution to a
      lysosomal membrane protein (LAMP-1) that is transferred to the plasma membrane by
      exocytosis. We used TALL-104 human leukemic CTLs stimulated with soluble
      chemicals. Using high-throughput cluster cytometry to screen 364,202 compounds in
      a 1536-well plate format, we identified 2404 initial hits: 161 were confirmed on
      retesting, and dose-response measurements were performed. Seventy-five of those
      compounds were obtained, and 48 were confirmed active. Experiments were conducted
      to determine the molecular mechanism of action (MMOA) of the active compounds.
      Fifteen blocked increases in intracellular calcium >50%. Seven blocked
      phosphorylation of extracellular signal-regulated kinase (ERK) by upstream
      mitogen-activated protein kinase kinases >50%. One completely blocked the
      activity of the calcium-dependent phosphatase calcineurin. None blocked ERK
      catalytic activity. Eight blocked more than one pathway. For 8 compounds, we were
      unable to determine an MMOA. The activity of 1 of these compounds was confirmed
      from powder resupply. We conclude that a screen based on antibody binding to CTLs
      is a good means of identifying novel candidate immunosuppressants with either
      known or unknown MMOAs. 

PMID- 25381255
TI  - The acute extracellular flux (XF) assay to assess compound effects on
      mitochondrial function.
AB  - Numerous investigations have linked mitochondrial dysfunction to adverse health
      outcomes and drug-induced toxicity. The pharmaceutical industry is challenged
      with identifying mitochondrial liabilities earlier in drug development and
      thereby reducing late-stage attrition. Consequently, there is a demand for
      reliable, higher-throughput screening methods for assessing the impact of drug
      candidates on mitochondrial function. The extracellular flux (XF) assay described
      here is a plate-based method in which galactose-conditioned HepG2 cells were
      acutely exposed to test compounds, then real-time changes in the oxygen
      consumption rate and extracellular acidification rate were simultaneously
      measured using a Seahorse Bioscience XF-96 analyzer. The acute XF assay was
      validated using marketed drugs known to modulate mitochondrial function, and data
      analysis was automated using a spline curve fitting model developed at
      GlaxoSmithKline. We demonstrate that the acute XF assay is a robust, sensitive
      screening platform for evaluating drug-induced effects on mitochondrial activity
      in whole cells. 

PMID- 25381256
TI  - Application of the mirrorball high-sensitivity cytometer to multiplexed assays
      for antibody drug discovery.
AB  - Highly sensitive, high-throughput assay technologies are required for the
      identification of antibody therapeutics. Multiplexed assay systems are
      particularly advantageous because they allow evaluation of several parameters
      within 1 well, increasing throughput and reducing hands-on laboratory time. The
      mirrorball (TTP Labtech), using high-throughput fluorometric microvolume assay
      technology, offers simultaneous scanning with up to 3 lasers as well as laser
      scatter detection. This makes the mirrorball especially suitable for the
      development of highly sensitive and multiplexed assays. We have developed bead-
      and cell-based binding assays that demonstrate how the multilaser capability of
      the mirrorball can be exploited to enhance assay sensitivity. In addition, using
      the multilaser simultaneous scanning capability, we have established multiplexed
      cytokine quantitation assays and antibody-cell binding assays. Our results
      demonstrate the potential utility of this technology to improve the sensitivity
      and efficiency of biologics screening, resulting in streamlining of the lead
      antibody selection process. 

PMID- 25381257
TI  - Open access to high-content clonogenic analysis.
AB  - Image-processing programs are used to identify and classify eukaryotic cell
      colonies as spots following seeding at low density on dishes or in multiwell
      plates. The output from such approaches, however, is generally limited to 1-2
      parameters, and there is no ability to extract phenotypic information at the
      single colony level. Furthermore, there is a lack of user-friendly pipelines for
      analysis of clonogenicity in the context of high-content analysis. This article
      describes an experimental and multiparametric image analysis workflow for
      clonogenic assays in multiwell format, named the Colony Assay Toolbox (CAT). CAT
      incorporates a cellular-level resolution of individual colonies and facilitates
      the extraction of phenotypic information, including the number and size of
      colonies and nuclei, as well as morphological parameters associated with each
      structure. Furthermore, the pipeline is capable of discriminating between
      colonies composed of senescent and nonsenescent cells. We demonstrate the
      accuracy and flexibility of CAT by interrogating the effects of 2 preclinical
      compounds, Nutlin-3a and ABT-737, on the growth of human osteosarcoma cells. CAT
      is accessible to virtually all laboratories because it uses common wide-field
      fluorescent microscopes, the open-source CellProfiler program for colony image
      analysis, and a single fluorescent dye for all the segmentation steps. 

PMID- 25381258
TI  - Extrafloral nectar fuels ant life in deserts.
AB  - Interactions mediated by extrafloral nectary (EFN)-bearing plants that reward
      ants with a sweet liquid secretion are well documented in temperate and tropical
      habitats. However, their distribution and abundance in deserts are poorly known.
      In this study, we test the predictions that biotic interactions between EFN
      plants and ants are abundant and common also in arid communities and that EFNs
      are only functional when new vegetative and reproductive structures are
      developing. In a seasonal desert of northwestern Argentina, we surveyed the
      richness and phenology of EFN plants and their associated ants and examined the
      patterns in ant-plant interaction networks. We found that 25 ant species and 11
      EFN-bearing plant species were linked together through 96 pairs of associations.
      Plants bearing EFNs were abundant, representing ca. 19 % of the species
      encountered in transects and 24 % of the plant cover. Most ant species sampled
      (ca. 77 %) fed on EF nectar. Interactions showed a marked seasonal pattern: EFN
      secretion was directly related to plant phenology and correlated with the time of
      highest ant ground activity. Our results reveal that EFN-mediated interactions
      are ecologically relevant components of deserts, and that EFN-bearing plants are
      crucial for the survival of desert ant communities. 

PMID- 25381259
TI  - Light-dark O2 dynamics in submerged leaves of C3 and C4 halophytes under
      increased dissolved CO2: clues for saltmarsh response to climate change.
AB  - Waterlogging and submergence are the major constraints to which wetland plants
      are subjected, with inevitable impacts on their physiology and productivity.
      Global warming and climate change, as driving forces of sea level rise, tend to
      increase such submersion periods and also modify the carbonate chemistry of the
      water column due to the increased concentration of CO2 in the atmosphere. In the
      present work, the underwater O2 fluxes in the leaves of two abundant
      Mediterranean halophytes were evaluated at different levels of dissolved CO2.
      Photosynthetic enhancement due to increased dissolved CO2 was confirmed for both
      Halimione portulacoides and Spartina maritima, probably due to high tissue
      porosity, formation of leaf gas films and reduction of the oxygenase activity of
      Rubisco. Enhancement of the photosynthetic rates in H. portulacoides and S.
      maritima was concomitant with an increase in energy trapping and transfer, mostly
      due to enhancement of the carboxylation reaction of Rubisco, leading to a
      reduction of the energy costs for carbon fixation. Transposing these findings to
      the ecosystem, and assuming increased dissolved CO2 concentration scenarios, the
      halophyte community displays a new ecosystem function, increasing the water
      column oxygenation and thus reinforcing their role as principal primary producers
      of the estuarine system. 

PMID- 25381261
TI  - Darinaparsin inhibits prostate tumor-initiating cells and Du145 xenografts and is
      an inhibitor of hedgehog signaling.
AB  - Prostate cancer is the leading cause of cancer-related death in men in the United
      States. A major cause of drug resistance in prostate and other epithelial tumors
      may be due to the presence of a fraction of tumor cells that retain the ability
      to initiate tumors and hence are termed tumor-initiating cells (TIC) or cancer
      stem cells. Here, we report that darinaparsin, an organic derivative of arsenic
      trioxide, is cytotoxic to prostate cancer cell lines as well as fresh prostate
      cancer cells from patients at low micromolar concentrations, and importantly
      inhibits the TIC subpopulations. It also inhibits growth of the castrate
      resistant Du145 prostate tumor propagated as xenograft in mice and inhibits the
      tumor-initiating potential of prostate cancer cells. Although the mechanism by
      which darinaparsin acts is not completely known, we show that it kills prostate
      cancer cells by blocking cells in the G2-M phase of the cell cycle and inhibits
      Hedgehog signaling by downregulating Gli-2 transcriptional activity. These data
      provide a rationale for evaluating darinaparsin in patients with castrate
      resistant prostate cancer.

PMID- 25381260
TI  - A role for Saccharomyces cerevisiae Tpa1 protein in direct alkylation repair.
AB  - Alkylating agents induce cytotoxic DNA base adducts. In this work, we provide
      evidence to suggest, for the first time, that Saccharomyces cerevisiae Tpa1
      protein is involved in DNA alkylation repair. Little is known about Tpa1 as a
      repair protein beyond the initial observation from a high-throughput analysis
      indicating that deletion of TPA1 causes methyl methane sulfonate sensitivity in
      S. cerevisiae. Using purified Tpa1, we demonstrate that Tpa1 repairs both single-
      and double-stranded methylated DNA. Tpa1 is a member of the Fe(II) and 2
      oxoglutarate-dependent dioxygenase family, and we show that mutation of the amino
      acid residues involved in cofactor binding abolishes the Tpa1 DNA repair
      activity. Deletion of TPA1 along with the base excision repair pathway DNA
      glycosylase MAG1 renders the tpa1Deltamag1Delta double mutant highly susceptible
      to methylation-induced toxicity. We further demonstrate that the trans-lesion
      synthesis DNA polymerase Polzeta (REV3) plays a key role in tolerating DNA methyl
      base lesions and that tpa1Deltamag1revDelta3 triple mutant is extremely
      susceptible to methylation-induced toxicity. Our results indicate a synergism
      between the base excision repair pathway and direct alkylation repair by Tpa1 in
      S. cerevisiae. We conclude that Tpa1 is a hitherto unidentified DNA repair
      protein in yeast and that it plays a crucial role in reverting alkylated DNA base
      lesions and cytotoxicity. 

PMID- 25381263
TI  - Bicyclic peptides conjugated to an albumin-binding tag diffuse efficiently into
      solid tumors.
AB  - Monoclonal antibodies have long in vivo half-lives and reach high concentrations
      in tumors but cannot access all regions in the tissue, whereas smaller ligands
      such as peptides distribute better but are limited by low concentrations due to
      fast renal clearance. A potential solution to this problem might be offered by
      peptide-based ligands that are conjugated to an albumin-binding tag, and thus
      have a long plasma half-life. Herein, we tested if a small ligand based on a
      bicyclic peptide (1.9 kDa) conjugated to an albumin-binding peptide (2.3 kDa) can
      diffuse into tissues. Although the peptide conjugate (4.6 kDa) was most of the
      time bound to the large protein serum albumin (66.5 kDa), it diffused deeply into
      tissues and reached high nanomolar concentrations in wide areas of solid tumors.
      Most of the peptide conjugate isolated from tumor tissue was found to be fully
      intact 24 hours after administration. Because of its noncovalent interaction with
      albumin, the bicyclic peptide might dissociate to diffuse to tumor regions that
      are not accessible to larger ligands. Bicyclic peptides having high binding
      affinity for targets of interest and being proteolytically stable can be evolved
      by phage display; in conjunction with albumin-binding tags, they offer a
      promising format to access targets in solid tumors.

PMID- 25381262
TI  - Identifying actionable targets through integrative analyses of GEM model and
      human prostate cancer genomic profiling.
AB  - Copy-number alterations (CNA) are among the most common molecular events in human
      prostate cancer genomes and are associated with worse prognosis. Identification
      of the oncogenic drivers within these CNAs is challenging due to the broad nature
      of these genomic gains or losses which can include large numbers of genes within
      a given region. Here, we profiled the genomes of four genetically engineered
      mouse prostate cancer models that reflect oncogenic events common in human
      prostate tumors, with the goal of integrating these data with human prostate
      cancer datasets to identify shared molecular events. Met was amplified in 67% of
      prostate tumors from Pten p53 prostate conditional null mice and in approximately
      30% of metastatic human prostate cancer specimens, often in association with loss
      of PTEN and TP53. In murine tumors with Met amplification, Met copy-number gain
      and expression was present in some cells but not others, revealing intratumoral
      heterogeneity. Forced MET overexpression in non-MET-amplified prostate tumor
      cells activated PI3K and MAPK signaling and promoted cell proliferation and tumor
      growth, whereas MET kinase inhibition selectively impaired the growth of tumors
      with Met amplification. However, the impact of MET inhibitor therapy was
      compromised by the persistent growth of non-Met-amplified cells within Met
      amplified tumors. These findings establish the importance of MET in prostate
      cancer progression but reveal potential limitations in the clinical use of MET
      inhibitors in late-stage prostate cancer.

PMID- 25381264
TI  - Combination strategy targeting VEGF and HGF/c-met in human renal cell carcinoma
      models.
AB  - Alternative pathways to the VEGF, such as hepatocyte growth factor or HGF/c-met,
      are emerging as key players in tumor angiogenesis and resistance to anti-VEGF
      therapies. The aim of this study was to assess the effects of a combination
      strategy targeting the VEGF and c-met pathways in clear cell renal cell carcinoma
      (ccRCC) models. Male SCID mice (8/group) were implanted with 786-O tumor pieces
      and treated with either a selective VEGF receptor tyrosine kinase inhibitor,
      axitinib (36 mg/kg, 2*/day); a c-met inhibitor, crizotinib (25 mg/kg, 1*/day); or
      combination. We further tested this drug combination in a human ccRCC patient
      derived xenograft, RP-R-01, in both VEGF-targeted therapy-sensitive and 
      resistant models. To evaluate the resistant phenotype, we established an RP-R-01
      sunitinib-resistant model by continuous sunitinib treatment (60 mg/kg, 1*/day) of
      RP-R-01-bearing mice. Treatment with single-agent crizotinib reduced tumor
      vascularization but failed to inhibit tumor growth in either model, despite also
      a significant increase of c-met expression and phosphorylation in the sunitinib
      resistant tumors. In contrast, axitinib treatment was effective in inhibiting
      angiogenesis and tumor growth in both models, with its antitumor effect
      significantly increased by the combined treatment with crizotinib, independently
      from c-met expression. Combination treatment also induced prolonged survival and
      significant tumor growth inhibition in the 786-O human RCC model. Overall, our
      results support the rationale for the clinical testing of combined VEGF and HGF/c
      met pathway blockade in the treatment of ccRCC, both in first- and second-line
      setting.

PMID- 25381265
TI  - Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.
AB  - Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and
      inactivates platelet-activating factor (PAF) and was previously suggested to have
      anticancer properties. The direct evidence is still lacking. We studied colonic
      tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci
      (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM
      alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced
      AOM/DSS method. beta-Catenin was determined by immunohistochemistry, PAF levels
      by ELISA, and sphingomyelin metabolites by mass spectrometry. Without treatment,
      spontaneous tumorigenesis was not identified but the intestinal mucosa appeared
      thicker in KO than in wild-type (WT) littermates. AOM alone induced more ACF in
      KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS
      treatments induced colonic tumors and the incidence was significantly higher in
      KO than in WT mice. By the enhanced AOM/DSS method, tumor number per mouse
      increased 4.5 times and tumor size 1.8 times in KO compared with WT mice.
      Although all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO
      mice. Compared with WT mice, cytosol expression of beta-catenin was significantly
      increased and nuclear translocation in tumors was more pronounced in KO mice.
      Lipid analysis showed decreased ceramide in small intestine and increased
      sphingosine-1-phosphate (S1P) in both small intestine and colon in nontreated KO
      mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS
      treatment. In conclusion, lack of alk-SMase markedly increases AOM/DSS-induced
      colonic tumorigenesis associated with decreased ceramide and increased S1P and
      PAF levels.

PMID- 25381266
TI  - Factors Mediating the Relationship Between Intimate Partner Violence and Cervical
      Cancer Among Thai Women.
AB  - Previous research suggests that intimate partner violence (IPV), particularly
      physical or sexual violence, was associated with cervical cancer. However, there
      is less work examining the mechanism of the relationship between IPV and cervical
      cancer. The purpose of this cross-sectional study was to examine psychosocial
      factors (e.g., stress, social support, self-esteem, and depressive symptoms) as
      mediators of the relationship between IPV and cervical cancer among 532 Thai
      women with gynecological problems. About 21.1% of participants reported any type
      of IPV (e.g., physical, sexual, or emotional violence) in the past year and 22.2%
      had cervical cancer. IPV was significantly positively associated with stress,
      depressive symptoms, and cervical cancer but negatively correlated with social
      support and self-esteem. Results from structural equation modeling indicated that
      not only did IPV exhibit significantly direct effects on social support, stress,
      and depressive symptoms, and indirect effects on self-esteem, but it also had a
      significant, positive, total effect on cervical cancer. IPV exhibited the
      significant indirect effect on cervical cancer through social support, self
      esteem, stress, and depressive symptoms. The model fitted very well to the
      empirical data and explained 9% of variance. The findings affirmed that those
      psychosocial factors were mediators of the relationship between IPV and cervical
      cancer. Health care protocols for abused women should include screening for and
      treatment of IPV-related psychosocial factors. Interventions that provide social
      support and protect self-esteem should reduce stress and depressive symptoms
      among abused women, thereby reducing the risk of cervical cancer.

PMID- 25381267
TI  - Determinants of Intimate Partner Violence Among HIV-Positive and HIV-Negative
      Women in India.
AB  - To reduce the many adverse health outcomes associated with intimate partner
      violence (IPV), high-risk groups need to be specifically targeted in the fight
      against domestic violence in India. This study aims to examine the prevalence and
      correlates of IPV in HIV-positive and HIV-negative women from India. A
      convenience sample of HIV-positive and HIV-negative women responded to
      questionnaires to assess their experience and perception of violence.
      Multivariate logistic regression analysis was used to model the association
      between IPV and age, education, employment status, contraception use, age at
      first marriage, and HIV status. Although adjusting for age, education, employment
      status, contraception use, age at first marriage, and HIV status, women who are
      employed were 3.5 times more likely to suffer IPV (confidence interval [CI] =
      [1.5, 8.5]), women aged 18 or above at first marriage are 0.3 times less likely
      to face IPV (CI = [0.1, 0.6]), and women who use contraception are 7 times more
      likely to suffer IPV (CI = [1.4, 30.2]). Also, HIV-positive women are 3 times
      more likely to face sexual violence compared with HIV-negative women (CI = [1.1,
      7.6]). 

PMID- 25381268
TI  - Delinquent and Aggressive Behavior and Social Desirability Among Roma and Non
      Roma Adolescents in Slovakia: A Cross-Sectional Study.
AB  - Rates of aggression and delinquency are assumed to be higher among Roma and other
      minorities, but sound evidence of this is lacking. Our aim was to assess
      delinquent and aggressive behavior among Roma and non-Roma adolescents and the
      effects on ethnic differences of parental education and social desirability. We
      conducted a cross-sectional study among Roma from separated and segregated
      settlements in the eastern part of Slovakia (N = 330; Mage = 14.50; interview)
      and non-Roma adolescents (N = 722; Mage = 14.86; questionnaire). The effect of
      ethnicity on antisocial behaviors was analyzed using linear regression (crude)
      and adjusted for gender, parental education, and social desirability. Adjustment
      for social desirability diminished the ethnic differences in delinquency (B =
      1.08; 95% confidence interval [CI] = [2.12, -0.04]), led to an increase in the
      differences in hostility (B = 2.43; 95% CI = [0.87, 3.99]), and led to the
      disappearance of differences in physical aggression (B = 0.45; 95% CI = [1.14,
      2.07]). Parental education did not affect the associations in an important way.
      Our findings indicate that Roma are not that much different from non-Roma, in
      terms of antisocial behavior, which contradicts the general perception of Roma.
      Our findings should be confirmed in other settings.

PMID- 25381269
TI  - Rape as an Economic Crime: The Impact of Sexual Violence on Survivors' Employment
      and Economic Well-Being.
AB  - This article examines how isolated instances of sexual violence affect adult
      female survivors' employment and economic well-being. This study draws on data
      from 27 in-depth, qualitative interviews with sexual assault survivors and rape
      crisis service providers. The findings suggest that sexual assault and the
      related trauma response can disrupt survivors' employment in several ways,
      including time off, diminished performance, job loss, and inability to work. By
      disrupting income or reducing earning power, all of these employment consequences
      have implications for survivors' economic well-being in the months or years
      following the assault. In addition, I argue that for many survivors, these
      employment consequences compound one another and ultimately shift survivors' long
      term economic trajectories. By highlighting survivors' lived experiences of the
      financial aftermath of sexual assault, these findings help to illuminate the
      processes by which sexual violence decreases survivors' income over the life
      course. Understanding the financial effects of sexual violence can help
      researchers better understand and predict the recovery process, while helping
      practitioners to design more effective interventions for survivors. 

PMID- 25381270
TI  - "Strength at Home" Intervention for Male Veterans Perpetrating Intimate Partner
      Aggression: Perceived Needs Survey of Therapists and Pilot Effectiveness Study.
AB  - Veteran and active duty populations evidence higher rates of intimate partner
      aggression (IPA) than comparable civilian groups, perhaps due in part to their
      unique service-related experiences. IPA offender treatment programs that take
      military background into consideration are not widely available, and it is
      unclear to what extent there is a perceived need for them among clinicians who
      serve service members and Veterans. Strength at Home (SAH) is a promising 12
      session cognitive-behavioral group intervention designed to address IPA
      perpetration in military populations. While clinical support for SAH is emerging,
      the extent to which service members and Veterans find it appropriate and helpful
      is not yet known. Goals of the current study were threefold: (a) assess the
      perceived need for a military-specific IPA program among Veterans Administration
      and community domestic violence (DV) program providers; (b) conduct a pilot study
      to examine the feasibility and preliminary effectiveness of SAH in a sample drawn
      from a diverse, multicultural community; and (c) conduct focus groups to obtain
      participant feedback on the SAH protocol. Findings from the provider survey
      suggested a need for specialty programs to treat military personnel who
      perpetrate IPA of mildtomoderate severity. Results of the SAH pilot study (n = 6)
      indicated decreased psychological aggression and increased anger control from
      baseline to 6-month follow-up. Focus group feedback indicated participants found
      the program to be helpful and appropriate across a wide variety of ethno-cultural
      variables. As more service members and Veterans of the Iraq/Afghanistan war era
      reintegrate into our communities, it will become increasingly important for
      providers in both private and public sectors of care to understand the unique
      needs of this treatment population, and to have access to effective IPA treatment
      programs.

PMID- 25381271
TI  - Survivor-Defined Practice in Domestic Violence Work: Measure Development and
      Preliminary Evidence of Link to Empowerment.
AB  - Survivor-defined practice, characterized by an emphasis on client choice,
      partnership, and sensitivity to the unique needs, contexts, and coping strategies
      of individual survivors, is an aspirational goal of the domestic violence (DV)
      movement, assumed to be a key contributor to empowerment and other positive
      outcomes among survivors. Despite its central role in DV program philosophy,
      training, and practice, however, our ability to assess its presence and its
      presumed link to well-being has been hampered by the absence of a way to measure
      it from survivors' perspectives. As part of a larger university-community
      collaboration, this study had two aims: (a) to develop a measure of survivor
      defined practice from the perspective of participants, and (b) to assess its
      relationship to safety-related empowerment after controlling for other
      contributors to survivor well-being (e.g., financial stability and social
      support). Results supported the reliability and validity of the Survivor-Defined
      Practice Scale (SDPS), a nine-item measure that assesses participants' perception
      of the degree to which their advocates help them achieve goals they set for
      themselves, facilitate a spirit of partnership, and show sensitivity to their
      individual needs and styles. The items combined to form one factor indicating
      that the three theoretical aspects of survivor-defined practice may be different
      manifestations of one underlying construct. Results also support the hypothesized
      link between survivor-defined practice and safety-related empowerment. The SDPS
      offers DV programs a mechanism for process evaluation that is rigorous and rooted
      in the feminist empowerment philosophy that so many programs espouse. 

PMID- 25381272
TI  - Is Routine Screening for Intimate Partner Violence Feasible in Public Health Care
      Settings in Kenya?
AB  - More than a third of women worldwide have experienced either physical and/or
      sexual intimate partner violence (IPV) or non-partner sexual violence. The short-
      and long-term health effects of violence can be disabling if left undetected. A
      recent World Health Organization (WHO) report indicates that Africa is one of the
      regions with the highest prevalence of physical and/or sexual IPV among ever
      partnered women. Routine screening for IPV can potentially improve the care and
      treatment of women suffering from violence. Although routine screening is
      commonplace in European and American countries, health systems barriers in
      developing countries have deterred introduction of this practice. Results from
      this feasibility study indicate that providers are willing and able to
      incorporate IPV screening into their practice and that IPV screening in a variety
      of health care settings in a public hospital is feasible and welcomed by clients.
      Referral uptake by women suffering from IPV was low compared with provider
      referral rates, but ways in which referral and management services could be
      improved were identified. 

PMID- 25381274
TI  - Torture and Long-Term Health Effects Among Lebanese Female Political Prisoners.
AB  - Lebanese prisoners during the Israeli occupation of Lebanon (1981-1999) were
      subject to regular torture. We examined the association between torture events
      and post-traumatic stress and cardiovascular diseases (CVDs) among former women
      political prisoners. We conducted a retrospective survey and performed health
      check-ups among 108 former women prisoners. Post-traumatic stress disorder (PTSD)
      was measured through the Clinician-Administered PTSD Scale (CAPS), and CVDs were
      assessed by physicians' diagnoses. The study was conducted between September 2008
      and March 2010. All 67 participants in the study reported having been subjected
      to a variety of torture events. The prevalence of PTSD was 28.4% and that of CVD
      was 16.42%, respectively. PTSD and CVD were more likely to occur among women who
      had had longer imprisonment periods, and PTSD specifically was associated with
      exposure to torture (beating: OR = 1.49; 95% CI [0.48, 4.27] and threatening by
      rape: OR = 1.43; 95% CI [0.82, 9.30]). CVD was associated with asphyxia with
      water (OR = 3.86; 95% CI [0.03, 2.28]). Devoutness decreased the risk of PTSD (OR
      = 0.24; 95% CI [0.08, 1.41]). Torture had adverse long-term effects on prisoners'
      physiological and psychological health; devoutness played a significant
      protective role. This study highlights the importance of documenting torture
      events and identifying the indicators of associated morbidity among surviving
      political prisoners for the provision of additional resources to care. 

PMID- 25381273
TI  - Enacted Sexual Stigma, Stigma Consciousness, and Subjective Happiness Scale
      Adaptation: A Two-Country Study.
AB  - Violence against people due to their sexual orientation is a phenomenon that
      exists within a framework of sexual stigma and sexual prejudice that can result
      in enacted stigma. The present study primarily aimed to validate the Stigma
      Consciousness Questionnaire (SCQ) and the Subjective Happiness Scale (SHS; for
      lesbian, gay, and bisexual [LGB] populations) in the Spanish context by using
      samples from two countries (Spain [N = 157] and the United States [N = 83]).
      Also, to examine how the construct of stigma consciousness correlates with anti
      LGBQ (anti-lesbian, gay, bisexual, and queer) hate crime victimization and
      violent incidents, as well as examine whether the former influences subjective
      happiness. The population from the United States reported higher stigma
      consciousness and received more anti-LGBQ threats and insults. Hate crime
      victimization was the same across the two samples and positively correlated with
      violent incidents in both samples. Subjective happiness was negatively correlated
      with SCQ, although its subscales it did not correlate with enacted stigma
      measures. 

PMID- 25381275
TI  - The Trauma of Commercial Sexual Exploitation of Youth: A Comparison of CSE
      Victims to Sexual Abuse Victims in a Clinical Sample.
AB  - This study examined the demographic features, trauma profiles, clinical severity
      indicators, problem behaviors, and service utilization characteristics of youth
      victims of commercial sexual exploitation (CSE) compared with a matched sample of
      sexually abused/assaulted youth who were not exploited in commercial sex.
      Secondary data analysis and propensity score matching were used to select a
      sample of 215 help-seeking youth who were exploited in prostitution (n = 43) or
      who were sexually abused/assaulted but not exploited in prostitution (n = 172)
      from the National Child Traumatic Stress Network Core Data Set (NCTSN CDS).
      Propensity Score Matching was used to select a comparison sample based on age,
      race, ethnicity, and primary residence. Statistically significant differences
      were noted between the groups on standardized (e.g., UCLA Posttraumatic Stress
      Disorder Reaction Index [PTSD-RI], Child Behavior Checklist [CBCL]) and other
      measures of emotional and behavioral problems (e.g., avoidance and hyperarousal
      symptoms, dissociation, truancy, running away, conduct disorder, sexualized
      behaviors, and substance abuse). This study provides useful insight into the
      symptom and service utilization profiles of youth exploited in commercial sex as
      compared with youth with other types of sexually exploitive experiences. Targeted
      screening and event-sensitive measures are recommended to more accurately
      identify youth exploited in commercial sex. More research is needed to determine
      if and what modifications to trauma therapies may be required to address the more
      severe symptomatology and behavior problems associated with youth exploited in
      commercial sex. 

PMID- 25381276
TI  - The Shadow of Physical Harm? Examining the Unique and Gendered Relationship
      Between Fear of Murder Versus Fear of Sexual Assault on Fear of Violent Crime.
AB  - The shadow hypothesis regarding the impact of fear of sexual assault on fear of
      violent crime suggests that female fear of crime is characterized by concern
      about sexual assault as a contemporaneous victimization event during a violent
      crime event. Recent research has found that other types of crime, namely physical
      assault, may also be feared as a contemporaneous offense. We know of no research
      that has examined the unique impact of fear of murder versus fear of sexual
      assault on fear of violent crime. There is also a lack of research that explores
      how these two types of fear uniquely affect men and women. In addition to gender,
      we examine factors that have been suggested in previous research to correlate
      with fear of crime: race, victimization, vicarious victimization, and perceived
      risk. Through survey methodology, this research examines the unique relationship
      between both fear of murder and fear of sexual assault and fear of three types of
      violent crime for men and women. Results suggest differences in how fear of
      murder and fear of sexual assault are related to fear of other types of violence
      for men and women. Specifically, fear of murder is important in estimating male
      fear of robbery and aggravated assault. However, fear of sexual assault is almost
      as important as fear of murder for men in estimating fear of home invasion.
      Similarly, for women, fear of sexual assault and fear of murder both are
      significant factors associated with fear of violent crime, and differences
      between the levels of significance are marginal. This study is a first to examine
      whether murder may also be feared as a contemporaneous offense. The results are
      informative in identifying what drives fear of crime, particularly violent crime,
      for both men and women. Avenues for future research are discussed. 

PMID- 25381277
TI  - Toxic Knowledge: Self-Alteration Through Child Abuse Work.
AB  - The purpose of the present article is to examine the multiple ways in which the
      private lives of professionals are affected by involvement with child abuse
      intervention and prevention. Using a descriptive-phenomenological perspective and
      40 in-depth interviews with professionals to present a model based on qualitative
      data, we studied the ways in which child abuse professionals conceptualize,
      understand, and integrate their experiences into their personal and family lives.
      We find that the process of internalizing child abuse knowledge occurs in two
      domains: One affirms or denies the existence of the phenomenon; the other
      concerns the strategies used to contend with the effects of working in abuse.
      Knowledge of child abuse is toxic, in the sense that it serves as a catalyst
      leading to the alteration of one's self-perception and parental identity. We
      present a typology of self-alteration resulting from child abuse knowledge and
      describe the mechanism of this change. 

PMID- 25381278
TI  - Vulnerability and Mimicry as Predictive Axes in Cyberbullying.
AB  - The co-occurrence of bullying and cyberbullying in a dual society like the
      present calls for specific measures of intervention to be able to forestall the
      emergence of new problems and slow the increase and diversification of violent
      behavior. This study's objective was to determine whether the gender of those
      involved as well as the forms of aggression experienced both in presential and
      virtual scenarios are predictive indicators of the violent behavior of aggressive
      victims. The participant sample was 1,648 adolescents aged 12 to 16 years (48.9%
      girls). The instrument used was a questionnaire. The results show the existence
      of four categories of aggressive-victims resulting from the co-occurrence of
      presential and cyber contexts: aggressive-victims of bullying, cyberaggressive
      victims, aggressive-cybervictims, and cyberaggressive-cybervictims. Furthermore,
      three predictive indicators of the abusive behavior of the aggressive-victims in
      their different categories were identified: continuity between contexts, type of
      abuse suffered, and the gender of those involved. These indicators allow one to
      extract individual profiles of the different types of aggressive-victims, which
      facilitate, on one hand, the understanding of the processes of victimization and
      aggression that adolescents experience in both presential and cyber contexts,
      and, on the other, the design of programs and specific actions based on the
      characteristics of the adolescents and their previous experiences of
      victimization or cybervictimization. 

PMID- 25381279
TI  - Posttraumatic Stress Disorder as a Mediator Between Trauma Exposure and Comorbid
      Mental Health Conditions in North Korean Refugee Youth Resettled in South Korea.
AB  - A structural equation model was used to investigate the relationship between
      trauma exposure and comorbid mental health problems and the mediation effect of
      posttraumatic stress disorder (PTSD) between trauma and mental health variables.
      The research model is based on the stress-vulnerability conceptual framework in
      which PTSD as a comorbid disorder mediates the relationship between trauma
      exposure and mental health problems. A self-administered survey was administered
      to 144 North Korean refugee youth residing in South Korea. Trauma exposure, both
      interpersonal and noninterpersonal, had no direct relationship with comorbid
      mental health problems. However, interpersonal trauma contributed to comorbid
      mental health problems through PTSD, demonstrating the mediation effect of PTSD
      and supporting the stress-vulnerability hypothesis of the current research model.
      Clinical implications of the study and future direction for research are
      discussed. 

PMID- 25381280
TI  - Correlates of Self-Report of Rape Among Male School Adolescents in Ile-Ife,
      Nigeria.
AB  - This study examined male adolescents' self-report of rape of adolescent girls and
      the socio-demographic variables that correlated with self-report of rape.
      Descriptive-correlational design was used and the study was conducted in five
      public senior secondary schools in Ile-Ife, Nigeria. Three hundred and thirty
      eight male adolescents participated in the study. A structured questionnaire was
      used to collect data. Findings from the study revealed the mean age of the
      adolescent males to be 16 years, with the majority (73%) of them in the middle
      adolescent stage. Six percent of the adolescent males reported they had raped an
      adolescent girl in the past. Among the boys who reported rape, 55% reported they
      had raped their sexual partners, and 55% reported they had perpetrated gang rape.
      Smoking (p = .0001), alcohol consumption (p = .001), and birth order (p = .006)
      predicted self-report of rape. The coefficient of birth order showed that odds of
      self-report of rape by first-born male increases by 6 times compared with other
      children. Study findings also provided evidence that adolescent males are moving
      from lone rape to gang rape in intimate partner relationships. Male adolescents
      are important group to target in rape prevention programs.

PMID- 25381281
TI  - Please Tell! Barriers to Disclosing Sexual Victimization and Subsequent Social
      Support Perceived by Children and Adolescents.
AB  - The present study examines barriers to disclosing sexual victimization and
      perceived social support after disclosure from the perspective of children and
      adolescents. Forty-two children and adolescents aged 6 to 17 years participated
      in semistructured interviews about their history of sexual victimization, the
      delay of disclosure, barriers to disclosure, informal and formal recipients of
      disclosure, as well as abuse-specific social support as perceived by the
      recipients. The participants disclosed their victimization with a delay of
      approximately 17 months, ranging from immediate reporting to 10 years of
      nondisclosure. The most frequent reasons to withhold the information were
      feelings of shame and threats by the perpetrator. A majority felt that people
      believed and supported them after disclosing, but a considerable proportion of
      study participants reported a lack of perceived protection against recurring
      victimization. The results underline the importance of educating children and
      adolescents about sexual victimization and of encouraging the immediate reporting
      of critical incidents. Possibilities to address the barriers identified in this
      study are discussed. 

PMID- 25381282
TI  - The Good, the Bad, and the Incomprehensible: Typifications of Victims and
      Offenders as Antecedents of Beliefs About Sex Crime.
AB  - Public opinion has played a critical role in the development of sex crime laws.
      However, little scholarly work has focused directly on the origins of negative
      attitudes toward sex offenders. We address this research gap by developing and
      testing a theoretical account of such views. Drawing on recent national survey
      data, we examine the extent to which typifications about sexual victims and
      offenders--believing sex crime typically affects children and female victims and
      is committed by strangers--explain beliefs about the reformability of sex
      offenders, harm inflicted on victims, and the causes of offending. Results
      indicate that judging children to be typical targets of sex crimes is a key
      determinant of public views. We discuss the implications of our findings.

PMID- 25381283
TI  - Posttraumatic Stress Symptomatology in Pre-Hospital Emergency Care Professionals
      Assaulted by Patients and/or Relatives: Importance of Severity and Experience of
      the Aggression.
AB  - Exposure to violence from patients or relatives causes problems in emergency
      departments. To assess the development of posttraumatic symptoms in pre-hospital
      emergency care professionals assaulted by patients and/or relatives, it may be
      crucial to establish preventive measures at different levels. This study examined
      358 pre-hospital emergency care professionals assaulted by patients and/or
      relatives. The aims of the present study were (a) to assess the presence of
      posttraumatic symptoms and posttraumatic stress disorder (PTSD) and (b) identify
      compliance diagnoses for PTSD depending on the experience of aggression (presence
      of fear, helplessness, or horror during the aggression), the perceived severity
      of aggression, and socio-demographic variables (gender, age, profession,
      employment status, and work experience). The results show that the experience of
      aggression with fear, helplessness, or horror is associated with the presence of
      posttraumatic symptoms related to re-experiencing but is not related to avoidance
      and emotional numbing and arousal. Furthermore, the perception of aggression as
      severe was associated with the presence of symptoms related to re-experiencing.
      These results are presented and discussed. 

PMID- 25381284
TI  - A Patient-Centered Decision-Support Tool Informed by History of Interpersonal
      Violence: "Will This Treatment Work for Me?".
AB  - The Probability of Treatment Benefit (PTB) chart is a decision-support tool that
      quantifies, in absolute terms, the probability that an individual patient will
      benefit from a psychological treatment based on the individual's pre-treatment
      characteristics. The demand for such a tool has increased with the growing
      emphasis on personalized medicine and the need for selecting a treatment from an
      expanding list of evidence-based models. This method has the potential to provide
      clinicians and mental health consumers with a practical and interpretable means
      of comparing treatment options for individuals whose benefit from a particular
      treatment may differ substantially. We provide a practice update and demonstrate
      how to develop a PTB chart using data from a randomized controlled trial
      examining the efficacy of two approaches for treating posttraumatic stress
      disorder based on patients' pre-treatment exposure to multiple types of
      interpersonal violence. Step-by-step instructions for applying the PTB method are
      provided. 

PMID- 25381285
TI  - Individual-and Setting-Level Correlates of Secondary Traumatic Stress in Rape
      Crisis Center Staff.
AB  - Secondary traumatic stress (STS) is an issue of significant concern among
      providers who work with survivors of sexual assault. Although STS has been
      studied in relation to individual-level characteristics of a variety of types of
      trauma responders, less research has focused specifically on rape crisis centers
      as environments that might convey risk or protection from STS, and no research to
      knowledge has modeled setting-level variation in correlates of STS. The current
      study uses a sample of 164 staff members representing 40 rape crisis centers
      across a single Midwestern state to investigate the staff member-and agency-level
      correlates of STS. Results suggest that correlates exist at both levels of
      analysis. Younger age and greater severity of sexual assault history were
      statistically significant individual-level predictors of increased STS. Greater
      frequency of supervision was more strongly related to secondary stress for non
      advocates than for advocates. At the setting level, lower levels of supervision
      and higher client loads agency-wide accounted for unique variance in staff
      members' STS. These findings suggest that characteristics of both providers and
      their settings are important to consider when understanding their STS.

PMID- 25381286
TI  - Elder Mistreatment and Health Status of Rural Older Adults.
AB  - There is limited information on the nature of and health factors associated with
      elder mistreatment in rural areas. To address this gap in the literature, the
      current study described the nature of such mistreatment and investigated the
      association between different types of mistreatment and health factors among 897
      randomly selected elderly persons in rural India. The results show that elder
      mistreatment was widely prevalent (21%). Furthermore, the higher frequency of and
      simultaneous occurrence of multiple types of mistreatment (83.4%) suggest that
      mistreatment was a continuous stressor. The presence of overall mistreatment was
      positively associated with depression symptoms and subjective health status. The
      higher levels of chronicity and multiple mistreatments further increased
      depression symptoms and lowered the health status of those who were mistreated.
      Although women, more than men, were more likely to experience mistreatment,
      chronic mistreatment, and multiple mistreatments, there were no significant
      gender differences in the mistreatment-health relationship. These findings
      suggest that older adults with depression symptoms and poor health should be
      screened for mistreatment. 

PMID- 25381287
TI  - Are leftists more emotion-driven than rightists? The interactive influence of
      ideology and emotions on support for policies.
AB  - Although emotions and ideology are important factors guiding policy support in
      conflict, their interactive influence remains unclear. Based on prior findings
      that ideological leftists' beliefs are more susceptible to change than rightists'
      beliefs, we tested a somewhat counterintuitive extension that leftists would be
      more susceptible to influence by their emotional reactions than rightists. In
      three laboratory studies, inducing positive and negative emotions affected Jewish
      Israeli leftists', but not rightists', support for conciliatory policies toward
      an adversarial (Studies 1 and 3) and a non-adversarial (Study 2) outgroup. Three
      additional field studies showed that positive and negative emotions were related
      to leftists', but not rightists', policy support in positive as well as highly
      negative conflict-related contexts, among both Jewish (Studies 4 and 5) and
      Palestinian (Study 6) citizens of Israel. Across different conflicts, emotions,
      conflict-related contexts, and even populations, leftists' policy support changed
      in accordance with emotional reactions more than rightists' policy support. 

PMID- 25381289
TI  - Isolation of a novel lodging resistance QTL gene involved in strigolactone
      signaling and its pyramiding with a QTL gene involved in another mechanism.
AB  - Lodging has been a major roadblock to attaining increased crop productivity. In
      an attempt to understand the mechanism for culm strength in rice, we isolated an
      effective quantitative trait loci (QTL), STRONG CULM3 (SCM3), the causal gene of
      which is identical to rice TEOSINTE BRANCHED1 (OsTB1), a gene previously reported
      to positively control strigolactone (SL) signaling. A near-isogenic line (NIL)
      carrying SCM3 showed enhanced culm strength and increased spikelet number despite
      the expected decrease in tiller number, indicating that SL also has a positive
      role in enhancing culm strength and spikelet number. We produced a pyramiding
      line carrying SCM3 and SCM2, another QTL encoding APO1 involved in panicle
      development. The NIL-SCM2+SCM3 showed a much stronger culm than NIL-SCM2 and NIL
      SCM3 and an increased spikelet number caused by the additive effect of these
      QTLs. We discuss the importance of utilizing suitable alleles of these STRONG
      CULM QTLs without inducing detrimental traits for breeding.

PMID- 25381290
TI  - Screening_mgmt: a Python module for managing screening data.
AB  - High-throughput screening is an established technique in drug discovery and, as
      such, has also found its way into academia. High-throughput screening generates a
      considerable amount of data, which is why specific software is used for its
      analysis and management. The commercially available software packages are often
      beyond the financial limits of small-scale academic laboratories and,
      furthermore, lack the flexibility to fulfill certain user-specific requirements.
      We have developed a Python module, screening_mgmt, which is a lightweight tool
      for flexible data retrieval, analysis, and storage for different screening assays
      in one central database. The module reads custom-made analysis scripts and
      plotting instructions, and it offers a graphical user interface to import,
      modify, and display the data in a uniform manner. During the test phase, we used
      this module for the management of 10,000 data points of various origins. It has
      provided a practical, user-friendly tool for sharing and exchanging information
      between researchers. 

PMID- 25381291
TI  - Making sense of Islamic creationism in Europe.
AB  - Islamic creationism has been noted as a serious concern in Europe. There have
      been reports of boycotts of university evolution lectures and, in one extreme
      case, even a threat of violence. While religious objections are indeed at play in
      some cases, our understanding of the rise of Islamic creationism should also take
      into account socioeconomic disparities and its impact on education for Muslim
      minorities in Europe. Furthermore, the broader narrative of rejection of
      evolution in Europe, for some Muslims, may be bound up in reactions to the
      secular culture and in the formation of their own minority religious identity. On
      the other hand, the stories of Muslim rejection of evolution in media end up
      reinforcing the stereotype of Muslims as "outsiders" and a threat to the European
      education system. A nuanced understanding of this dynamic may benefit those who
      support both the propagation of good science and favor cultural pluralism. 

PMID- 25381292
TI  - Unique mode of chlamydia transmission.

PMID- 25381293
TI  - Tongue-tie and frenotomy in infants with breastfeeding difficulties: achieving a
      balance.
AB  - AIMS: Currently there is debate on how best to manage young infants with tongue
      tie who have breastfeeding problems. One of the challenges is the subjectivity of
      the outcome variables used to assess efficacy of tongue-tie division. This
      structured review documents how the argument has evolved. It proposes how best to
      assess, inform and manage mothers and their babies who present with tongue-tie
      related breastfeeding problems. METHODS: Databases were searched for relevant
      papers including Pubmed, Medline, and the Cochrane Library. Professionals in the
      field were personally contacted regarding the provision of additional data.
      Inclusion criteria were: infants less than 3 months old with tongue-tie and/or
      feeding problems. The exclusion criteria were infants with oral anomalies and
      neuromuscular disorders. RESULTS: There is wide variation in prevalence rates
      reported in different series, from 0.02 to 10.7%. The most comprehensive clinical
      assessment is the Hazelbaker Assessment Tool for lingual frenulum function. The
      most recently published systematic review of the effect of tongue-tie release on
      breastfeeding concludes that there were a limited number of studies with quality
      evidence. There have been 316 infants enrolled in frenotomy RCTs across five
      studies. No major complications from surgical division were reported. The
      complications of frenotomy may be minimised with a check list before embarking on
      the procedure. CONCLUSIONS: Good assessment and selection are important because
      50% of breastfeeding babies with ankyloglossia will not encounter any problems.
      We recommend 2 to 3 weeks as reasonable timing for intervention. Frenotomy
      appears to improve breastfeeding in infants with tongue-tie, but the placebo
      effect is difficult to quantify. Complications are rare, but it is important that
      it is carried out by a trained professional.

PMID- 25381294
TI  - Predicting prolonged recovery after concussion.

PMID- 25381295
TI  - Vigabatrin retinal toxicity in children with infantile spasms: An observational
      cohort study.
AB  - OBJECTIVES: To determine time to vigabatrin (VGB, Sabril; Lundbeck, Deerfield,
      IL) induced retinal damage in children with infantile spasms (IS) and to identify
      risk factors for VGB-induced retinal damage (VGB-RD). METHODS: Observational
      cohort study including 146 participants (68 female, 81 male) with IS, an age
      specific epilepsy syndrome of early infancy, treated with VGB. Participants
      ranged from 3 to 34.9 months of age (median 7.6 months). The median duration of
      VGB treatment was 16 months (range 4.6-78.5 months). Electroretinograms (ERGs)
      were performed according to the Standards of the International Society for
      Clinical Electrophysiology of Vision. Inclusion required baseline (pre-VGB or
      within 4 weeks of starting VGB treatment) and at least 2 follow-up ERGs.
      Significant reduction from baseline of the 30-Hz ERG flicker amplitude on 2
      consecutive visits identified VGB-RD. Kaplan-Meier survival analyses depicted the
      effect of duration of VGB on VGB-RD. RESULTS: These data represent the largest
      survival analysis of children treated with VGB who did not succumb to retinal
      toxicity during the study. Thirty of the 146 participants (21%) showed VGB-RD.
      The ERG amplitude reduced with duration of VGB treatment (p = 0.0004) with no
      recovery after VGB cessation. With 6 and 12 months of VGB treatment, 5.3% and
      13.3%, respectively, developed VGB-RD. There was neither effect of age of
      initiation of VGB treatment nor sex of the child on survival statistics and no
      significant effect of cumulative dosage on the occurrence of VGB-RD. CONCLUSIONS:
      Minimizing VGB treatment to 6 months will reduce the prevalence of VGB-RD in
      patients with IS.

PMID- 25381297
TI  - Complex antibody profiling to predict clinical outcome in childhood ADS.

PMID- 25381296
TI  - Early symptom burden predicts recovery after sport-related concussion.
AB  - OBJECTIVE: To identify independent predictors of and use recursive partitioning
      to develop a multivariate regression tree predicting symptom duration greater
      than 28 days after a sport-related concussion. METHODS: We conducted a
      prospective cohort study of patients in a sports concussion clinic. Participants
      completed questionnaires that included the Post-Concussion Symptom Scale (PCSS).
      Participants were asked to record the date on which they last experienced
      symptoms. Potential predictor variables included age, sex, score on symptom
      inventories, history of prior concussions, performance on computerized
      neurocognitive assessments, loss of consciousness and amnesia at the time of
      injury, history of prior medical treatment for headaches, history of migraines,
      and family history of concussion. We used recursive partitioning analysis to
      develop a multivariate prediction model for identifying athletes at risk for a
      prolonged recovery from concussion. RESULTS: A total of 531 patients ranged in
      age from 7 to 26 years (mean 14.6 +/- 2.9 years). The mean PCSS score at the
      initial visit was 26 +/- 26; mean time to presentation was 12 +/- 5 days. Only
      total score on symptom inventory was independently associated with symptoms
      lasting longer than 28 days (adjusted odds ratio 1.044; 95% confidence interval
      [CI] 1.034, 1.054 for PCSS). No other potential predictor variables were
      independently associated with symptom duration or useful in developing the
      optimal regression decision tree. Most participants (86%; 95% CI 80%, 90%) with
      an initial PCSS score of <13 had resolution of their symptoms within 28 days of
      injury. CONCLUSIONS: The only independent predictor of prolonged symptoms after
      sport-related concussion is overall symptom burden.

PMID- 25381298
TI  - Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and
      intellectual disability.
AB  - OBJECTIVE: To identify and characterize the molecular basis of a syndrome
      associated with myasthenia, cortical hyperexcitability, cerebellar ataxia, and
      intellectual disability. METHODS: We performed in vitro microelectrode studies of
      neuromuscular transmission, performed exome and Sanger sequencing, and analyzed
      functional consequences of the identified mutation in expression studies.
      RESULTS: Neuromuscular transmission at patient endplates was compromised by
      reduced evoked quantal release. Exome sequencing identified a dominant de novo
      variant, p.Ile67Asn, in SNAP25B, a SNARE protein essential for exocytosis of
      synaptic vesicles from nerve terminals and of dense-core vesicles from endocrine
      cells. Ca(2+)-triggered exocytosis is initiated when synaptobrevin attached to
      synaptic vesicles (v-SNARE) assembles with SNAP25B and syntaxin anchored in the
      presynaptic membrane (t-SNAREs) into an alpha-helical coiled-coil held together
      by hydrophobic interactions. Pathogenicity of the Ile67Asn mutation was confirmed
      by 2 measures. First, the Ca(2+) triggered fusion of liposomes incorporating v
      SNARE with liposomes containing t-SNAREs was hindered when t-SNAREs harbored the
      mutant SNAP25B moiety. Second, depolarization of bovine chromaffin cells
      transfected with mutant SNAP25B or with mutant plus wild-type SNAP25B markedly
      reduced depolarization-evoked exocytosis compared with wild-type transfected
      cells. CONCLUSION: Ile67Asn variant in SNAP25B is pathogenic because it inhibits
      synaptic vesicle exocytosis. We attribute the deleterious effects of the mutation
      to disruption of the hydrophobic alpha-helical coiled-coil structure of the SNARE
      complex by replacement of a highly hydrophobic isoleucine by a strongly
      hydrophilic asparagine.

PMID- 25381299
TI  - Epitope spreading as an early pathogenic event in pediatric multiple sclerosis.
AB  - OBJECTIVES: For most adults with initial clinical presentation of multiple
      sclerosis (MS), biological disease was likely initiated many years prior.
      Pediatric-onset MS provides an opportunity to study early disease processes.
      METHODS: Using antigen microarrays, including CNS-related proteins, lipids, and
      other autoantigens, we studied early immunologic events involved in clinical
      onset of pediatric MS. Serum samples were collected at the time of incident
      acquired CNS demyelinating syndromes (ADS) in children who, in subsequent
      prospective follow-up, were ascertained to have either pediatric MS (ADS-MS) or a
      monophasic illness (ADS-mono). Samples were obtained both at the time of ADS
      presentation and 3 months into follow-up. We used an initial training set of
      samples to implicate antibody signatures associated with each group, and then a
      test set. An additional set of follow-up samples (stability set) was used as a
      form of internal validation. RESULTS: Children with ADS-MS tended to have
      distinguishable serum antibody patterns both at the time of ADS presentation and
      3 months into follow-up. At the time of ADS, serum samples from patients with ADS
      MS or ADS-mono reacted against similar numbers of CNS antigens, although CNS
      antigens implicated in adult MS were more often targeted in children with ADS-MS.
      The follow-up ADS-MS samples reacted against a broader panel of CNS antigens,
      while corresponding ADS-mono samples exhibited a contraction of the initial
      antibody response. CONCLUSIONS: Our findings in this prospective cohort of
      pediatric-onset CNS demyelinating diseases point to an active process of epitope
      spreading during early stages of MS, not seen in monophasic CNS inflammatory
      conditions.

PMID- 25381301
TI  - Evolve or perish for coronary calcium imaging.

PMID- 25381300
TI  - Treatment of sporadic inclusion body myositis with bimagrumab.
AB  - OBJECTIVE: To study activin signaling and its blockade in sporadic inclusion body
      myositis (sIBM) through translational studies and a randomized controlled trial.
      METHODS: We measured transforming growth factor beta signaling by SMAD2/3
      phosphorylation in muscle biopsies of 50 patients with neuromuscular disease (17
      with sIBM). We tested inhibition of activin receptors IIA and IIB (ActRII) in 14
      patients with sIBM using one dose of bimagrumab (n = 11) or placebo (n = 3). The
      primary outcome was the change in right thigh muscle volume by MRI at 8 weeks.
      Lean body mass, strength, and function were secondary outcomes. Twelve of the
      patients (10 bimagrumab, 2 placebo) participated in a subsequent 16-week
      observation phase. RESULTS: Muscle SMAD2/3 phosphorylation was higher in sIBM
      than in other muscle diseases studied (p = 0.003). Eight weeks after dosing, the
      bimagrumab-treated patients increased thigh muscle volume (right leg +6.5%
      compared with placebo, p = 0.024; left leg +7.6%, p = 0.009) and lean body mass
      (+5.7% compared with placebo, p = 0.014). Subsequently, bimagrumab-treated
      patients had improved 6-minute walking distance, which peaked at 16 weeks
      (+14.6%, p = 0.008) compared with placebo. There were no serious adverse events;
      the main adverse events with bimagrumab were mild acne and transient involuntary
      muscle contractions. CONCLUSIONS: Transforming growth factor beta superfamily
      signaling, at least through ActRII, is implicated in the pathophysiology of sIBM.
      Inhibition of ActRII increased muscle mass and function in this pilot trial,
      offering a potential novel treatment of sIBM. CLASSIFICATION OF EVIDENCE: This
      study provides Class I evidence that for patients with inclusion body myositis,
      bimagrumab increases thigh muscle volume at 8 weeks.

PMID- 25381302
TI  - The association of left ventricular mass with coronary atherosclerosis and
      myocardial ischemia: cause and effect or simple association?

PMID- 25381303
TI  - Low- vs. standard-dose coronary artery calcium scanning.
AB  - AIMS: This study was designed to assess the accuracy of coronary artery calcium
      scans (CACS) acquired at radiation doses below mammography and low-dose lung
      scanning, compared with standard-dose CACS. METHODS AND RESULTS: CACS was
      performed in 102 consecutive patients at 120 kVp; all were imaged at standard
      dose mAs levels ranging from 30 to 80 mAs determined by their weight, with
      iterative reconstruction (IR) level 3, and at 50% of the standard-dose mAs with
      IR level 7 to compensate for the expected increased noise with lower mAs. The low
      vs. standard-dose mAs was 24.5 +/- 8.8 vs. 48.5 +/- 17.8 mAs (P < 0.0001), and
      the radiation exposure was 0.37 +/- 0.16 vs. 0.76 + 0.34 mSv (P < 0.0001). The
      Agatston score correlation between the low and high dose was excellent (r =
      0.998, P < 0.0001) over a range of scores from 0 to 2512. The weighted kappa for
      agreement of standard CAC risk categories was 0.95 (95% CI 0.83-0.97). The mean
      of the differences between individual low- and standard-dose Agatston scores was
      17.4 +/- 25.8, lower than the reported variability of two scans performed with
      the same mAs. CONCLUSION: There was excellent agreement of CACS-based risk
      classification at low and standard doses, with lower interscan variability than
      with reported identical doses. The low-dose CACS radiation exposure was less than
      the approved screening tools of mammography and low-dose lung scanning.

PMID- 25381304
TI  - Rasch Analysis of the Arabic Language Version of the Functional Disability
      Inventory.
AB  - It is important for the responsive and effective treatment of pediatric cancer
      patients that functional disability is successfully measured, but no measures of
      functional disability have been validated for use with Arabic-speaking children
      and adolescents. The purpose of this study was to examine the psychometric
      characteristics of the first Arabic translation of the Functional Disability
      Inventory (FDI). A methodological study limited to the secondary analysis of
      functional disability data on 62 pediatric patients in Lebanon using the rating
      scale model and WINSTEPS Rasch analysis software was used. Disordered responses
      to 4 FDI times suggest that the Arabic translation of the rating scale categories
      might need revision or supplementation with a visual analogue scale. The
      dimensionality of the FDI needs further exploration because principal component
      analyses of residuals suggested the presence of secondary and possibly higher
      order dimensions. Additional FDI items are needed to improve targeting if low
      levels of functional disability are demonstrated to be clinically important for
      patient assessment and pain management. The FDI-A is suitable for clinical
      assessment and for monitoring the outcomes of pain management in Lebanese
      pediatric cancer patients. Our findings support the construct validity of the FDI
      A and acceptable reliability for the 15-item scale, Cronbach alpha .93 and .85
      for 4 of the item subsets we examined. Rating scale categories and the
      dimensionality of the FDI-A require further examination. The clinical relevance
      of distinctions between levels of functional disability in children and
      adolescents with cancer pain remains to be established. 

PMID- 25381305
TI  - Out of sight, out of mind? The inclusion and identification of people with
      intellectual disability in public health research.
AB  - AIMS: Adults with intellectual disability experience substantial health
      inequities. Public health research aiming to improve the lives of this population
      group is needed. We sought to investigate the extent to which a sample of
      international public health research includes and identifies people with
      intellectual disability. METHODS: In this systematic review, we examined a select
      number of public health journals to determine (1) how often people with
      intellectual disability are explicitly included in randomised controlled trials
      (RCTs) and cohort studies and (2) how the presence of intellectual disability is
      identified and reported. RESULTS: Among eligible articles in these selected
      public health journals, it was found that cohort studies passively exclude people
      with intellectual disability, while RCTs actively exclude this population. Most
      general population articles that explicitly identified people with intellectual
      disability did so through self-report or proxy report and databases. CONCLUSIONS:
      A more extensive and adequate evidence base relating to the health of this
      overlooked population group is needed. A useful first step would be for
      researchers specialising in intellectual disability to identify how we can best
      assist mainstream researchers to include and identify people with intellectual
      disability in their population-level studies.

PMID- 25381306
TI  - Trends in Electronic Cigarette Use Among U.S. Adults: Use is Increasing in Both
      Smokers and Nonsmokers.
AB  - OBJECTIVES: We assessed trends in use of electronic cigarettes among U.S. adults,
      demographic predictors of use, and smoking status of current electronic cigarette
      users. METHODS: Mixed-mode surveys were used to obtain representative, cross
      sectional samples of U.S. adults in each of 4 years. RESULTS: Sample sizes for
      2010, 2011, 2012, and 2013 were 3,240, 3,097, 3,101, and 3,245, respectively.
      Ever use of electronic cigarettes increased from 1.8% (2010) to 13.0% (2013),
      while current use increased from 0.3% to 6.8%, p < .001. Prevalence of use
      increased significantly across all demographic groups. In 2013, current use among
      young adults 18-24 (14.2%) was higher than adults 25-44 (8.6%), 45-64 (5.5%), and
      65+ (1.2%). Daily smokers (30.3%) and nondaily smokers (34.1%) were the most
      likely to currently use e-cigarettes, compared to former smokers (5.4%) and never
      smokers (1.4%), p < .001. However, 32.5% of current electronic cigarette users
      are never- or former smokers. CONCLUSIONS: There has been rapid growth in ever
      and current electronic cigarette use over the past 4 years. Use is highest among
      young adults and current cigarette smokers. Although smokers are most likely to
      use these products, almost a third of current users are nonsmokers, suggesting
      that e-cigarettes contribute to primary nicotine addiction and to renormalization
      of tobacco use. Regulatory action is needed at the federal, state, and local
      levels to ensure that these products do not contribute to preventable chronic
      disease.

PMID- 25381307
TI  - Circadian rhythm of plasma and urinary angiotensinogen in healthy volunteers and
      in patients with chronic kidney disease.
AB  - The urinary angiotensinogen (AGT) excretion rate could be a novel biomarker for
      the intrarenal activity of the renin-angiotensin system. Little is known about
      the circadian rhythm of AGT levels in plasma or urine. In this short article,
      making use of data in plasma and urine of healthy volunteers and patients with
      chronic kidney diseases, we first report that we were unable to find evidence for
      a circadian rhythm of AGT under any condition. Next we critically discuss to what
      degree elevated urinary AGT levels might be considered an independent biomarker
      that is not simply the non-specific consequence of proteinuria. 

PMID- 25381308
TI  - Working Alliance and Its Relationship With Treatment Outcome in a Sample of
      Aboriginal and Non-Aboriginal Sexual Offenders.
AB  - The relationship that develops between a client and therapist is arguably one of
      the most important factors toward achieving positive outcomes from therapy. The
      present study examined the therapeutic alliance, as measured by Horvath and
      Greenberg's Working Alliance Inventory (WAI), as a function of Aboriginal
      ancestry and the relationship of alliance to important program outcomes, in a
      Canadian correctional sample of 423 treated sexual offenders. The men rated their
      primary therapists on the WAI 3 months into treatment. Higher self-report ratings
      on the WAI and its Task, Bond, and Goal subscales were associated with lower
      rates of treatment non-completion and longer stay in treatment. Aboriginal men
      scored significantly lower on the WAI's Bond subscale (i.e., the emotional
      connection between client and therapist) than non-Aboriginal men, although by and
      large, the offender sample as a whole otherwise registered fairly high mean
      scores on the tool. Aboriginal men scoring below the median on WAI total score
      had the highest rates of treatment non-completion. WAI total score and scores on
      the three subscales were unrelated to post-program recidivism in the community.
      Cultural implications for correctional client engagement and service delivery
      within the context of the risk-needs-responsivity model are discussed. 

PMID- 25381309
TI  - Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex
      vivo/in vitro exposure study in respiratory disease patients.
AB  - Zinc oxide (ZnO) nanoparticles are the mostly used engineered metal oxide
      nanoparticles in consumer products. This has increased the likelihood of human
      exposure to this engineered nanoparticle (ENPs) through different routes. At
      present, the majority of the studies concerning ZnO ENPs toxicity have been
      conducted using in vitro and in vivo systems. In this study, for the first time
      we assessed the effect of ZnO ENPs on the major cellular pathways in the
      lymphocytes of healthy individuals as well as in susceptible patients suffering
      from lung cancer, chronic obstructive pulmonary disease (COPD) and asthma. Using
      the differential expression analysis, we observed a significant (P < 0.05) dose
      dependent (10, 20 and 40 ug/ml for 6h) increase in the expression of tumour
      suppressor protein p53 (40, 60 and 110%); Ras p21 (30, 52 and 80%); c-Jun N
      terminal kinases; JNKs) (28, 47 and 78%) in lung cancer patient samples treated
      with ZnO ENPs compared to healthy controls. A similar trend was also seen in COPD
      patient samples where a significant (P < 0.05) dose-dependent increase in the
      expression of tumour suppressor protein p53 (26, 45 and 84%), Ras p21 (21, 40 and
      77%), JNKs (17, 32 and 69%) was observed after 6h of ZnO ENPs treatment at the
      aforesaid concentrations. However, the increase in the expression profile of
      tested protein was not significant in the asthma patients as compared to
      controls. Our results reiterate the concern about the safety of ZnO ENPs in
      consumer products and suggest the need for a complete risk assessment of any new
      ENPs before its use. 

PMID- 25381310
TI  - Role of base excision repair genes and proteins in gamma-irradiated resting human
      peripheral blood mononuclear cells.
AB  - Ionising radiation induces several isolated and clustered DNA lesions in human
      cells. Depending on the type of lesions, DNA repair pathways get activated to
      maintain the integrity of the genome. Base excision repair (BER) pathway is known
      to repair single-strand breaks and base damages through short- and long-patch
      genes and proteins. In the present study, attempt has been made to study the role
      of BER genes and proteins in resting human peripheral blood mononuclear cells
      (PBMCs) exposed to gamma radiation. Venous blood samples were collected from 20
      random and healthy individuals with written informed consent. Dose-response and
      time-dependent changes at the level of DNA damage, transcription and protein
      expression were studied in PBMC. Dose-response studies were done in PBMC exposed
      between 0.1 and 2.0 Gy, whereas time-dependent changes in post-irradiated PBMC
      were studied up to 240 min. Our results have shown a significant (P <= 0.05) dose
      dependent increase in the percentage of DNA in tail (%T) among the individuals
      studied. At transcriptional level, LIGASE3, MBD4 and LIGASE1 showed significant
      up-regulation (P <= 0.05) at 4h compared to 0h. Short-patch BER proteins such as
      OGG1 and LIGASE3 showed significant increase (P <= 0.05) in expression at lower
      doses (<0.6 Gy), whereas long-patch BER proteins such as MBD4, FEN1 and LIGASE1
      showed an increase in expression at higher doses (1.0 and 2.0 Gy), suggesting
      dose-dependent and pathway-specific role of BER proteins in human PBMCs at G0/G1.
      In conclusion, BER genes and proteins play an active role in repairing radiation
      induced DNA damage in resting PBMC, which has important biological significance
      in terms of DNA repair process in humans.

PMID- 25381311
TI  - RE: Recommendations, evaluation and validation of a semi-automated, fluorescent
      based scoring protocol for micronucleus testing in human cells (Mutagenesis, 29,
      155-164, 2014).

PMID- 25381312
TI  - Nucleoplasmic bridges and acrocentric chromosome associations as early markers of
      exposure to low levels of ionising radiation in occupationally exposed hospital
      workers.
AB  - Ionising radiation, with the contribution of telomere shortening, induces DNA
      double-strand breaks that result in chromosome end fusion, nucleoplasmic bridges
      (NPBs) and chromosome aberrations (ChAbs) as well as dicentric chromosomes. In
      order to investigate the chromosomal damage induced by occupational ionising
      radiation at low exposure levels, and to find early markers of health hazard,
      peripheral lymphocytes of occupationally exposed hospital workers were
      cytogenetically analysed. Results showed a significant difference in the
      frequency of ChAbs in exposed subjects relative to controls. A significant number
      of NPBs between nuclei of binucleated cultured lymphocytes from exposed subjects
      were also observed, as well as a consistent amount of acrocentric chromosomes
      with associations of their short arms. Excluding confounding factors, the
      frequencies of all these three biological endpoints differed significantly in
      exposed subjects from those in controls. Because the absence of telomeres and/or
      their short length could be a common root for both the findings, we utilised
      fluorescence in situ hybridisation technique with telomeric repeat as probe to
      demonstrate that, in exposed subjects, chromatin of short arms of involved
      acrocentric chromosomes did not exhibit a telomeric shortening but appeared
      strongly decondensed. This finding suggests that NPBs and telomeric acrocentric
      association should be regarded as early markers of exposure to low levels of
      ionising radiation and their increase should be seen as an early warning for the
      health of the involved workers. 

PMID- 25381313
TI  - "A spoonful of sugar helps the medicine go down": bitter masking by sucrose among
      children and adults.
AB  - Sweeteners are often added to liquid formulations of drugs but whether they
      merely make them better tasting or actually reduce the perception of bitterness
      remains unknown. In a group of children and adults, we determined whether adding
      sucrose to urea, caffeine, denatonium benzoate, propylthiouracil (PROP), and
      quinine would reduce their bitterness using a forced-choice method of paired
      comparisons. To better understand individual differences, adults also rated each
      solution using a more complex test (general Labeled Magnitude Scale [gLMS]) and
      were genotyped for the sweet taste receptor gene TAS1R3 and the bitter receptor
      TAS2R38. Sucrose suppressed the bitterness of each agent in children and adults.
      In adults, sucrose was effective in reducing the bitterness ratings from moderate
      to weak for all compounds tested, but those with the sensitive form of the sweet
      receptor reported greater reduction for caffeine and quinine. For PROP, sucrose
      was most effective for those who were genetically the most sensitive, although
      this did not attain statistical significance. Not only is the paired comparison
      method a valid tool to study how sucrose improves the taste of pediatric
      medicines among children but knowledge gleaned from basic research in bitter
      taste and how to alleviate it remains an important public health priority. 

PMID- 25381315
TI  - Low vitamin D concentrations may contribute to the increased risk of diabetes
      mellitus related to shift work.

PMID- 25381314
TI  - Psychological consequences of screening for cardiovascular risk factors in an un
      selected general population: results from the Inter99 randomised intervention
      study.
AB  - BACKGROUND: Concerns that general health checks, including screening for risk
      factors to ischemic heart disease (IHD), have negative psychological consequences
      seem widely unfounded; however, previous studies are only based on self-reports
      from participants. AIM: To investigate if risk factor screening in healthy adults
      leads to mental distress in the study population, independent of participation.
      METHODS: The Inter99 study (1999 - 2006) was a randomised intervention in the
      general population, aiming to prevent IHD by a healthier lifestyle. We included
      the whole study population, independent of participation (n = 60,915). We merged
      data with information on the use of psychotropic medication and/or
      hospitalisation due to psychiatric diagnoses, as retrieved from national
      registers in Denmark, 4 years before and 5 years after the study began. We
      conducted analyses using generalised estimating equations. RESULTS: There was no
      significant difference between the intervention and control groups in their use
      of antipsychotics, hypnotics/sedatives, antidepressants or anxiolytics. As
      regards admission to the hospital with mental disorders, no significant
      difference was seen. These findings were true based on a yearly basis, and when
      investigating both short-term and a long-term effects of the intervention. There
      was no interaction with socioeconomic status. Of the 918 persons with a
      psychiatric diagnosis before the study start, 303 (33%) were re-admitted in the
      intervention period. Pre-screening of psychological status did not influence the
      psychological impact of screening. CONCLUSIONS: This large, randomised
      intervention study supports that screening for risk factors to IHD does not
      increase mental distress, not even in the mentally or socioeconomically most
      vulnerable persons. This study included the whole Inter99 study population not
      only study participants.

PMID- 25381316
TI  - Author response: Low vitamin D concentrations may contribute to the increased
      risk of diabetes mellitus related to shift work.

PMID- 25381318
TI  - Needs, norms and nudges: the place of behaviour change in health promotion.

PMID- 25381317
TI  - Arabidopsis reduces growth under osmotic stress by decreasing SPEECHLESS protein.
AB  - Plants, which are sessile unlike most animals, have evolved a system to reduce
      growth under stress; however, the molecular mechanisms of this stress response
      are not well known. During programmed development, a fraction of the leaf
      epidermal precursor cells become meristemoid mother cells (MMCs), which are stem
      cells that produce both stomatal guard cells and epidermal pavement cells. Here
      we report that Arabidopsis plants, in response to osmotic stress, post
      transcriptionally decrease the protein level of SPEECHLESS, the transcription
      factor promoting MMC identity, through the action of a mitogen-activated protein
      kinase (MAPK) cascade. The growth reduction under osmotic stress was lessened by
      inhibition of the MAPK cascade or by a mutation that disrupted the MAPK target
      amino acids in SPEECHLESS, indicating that Arabidopsis reduces growth under
      stress by integrating the osmotic stress signal into the MAPK-SPEECHLESS core
      developmental pathway. 

PMID- 25381320
TI  - Kula B et Al (clin infect dis 2014; 59:1113-22).

PMID- 25381322
TI  - Editorial commentary: NOVA score to predict endocarditis in patients with
      enterococcal bacteremia: sticking to valves or to scores?

PMID- 25381323
TI  - Importance of peer review.

PMID- 25381321
TI  - The NOVA score: a proposal to reduce the need for transesophageal
      echocardiography in patients with enterococcal bacteremia.
AB  - BACKGROUND: Frequency of enterococcal bloodstream infection (E-BSI) is
      increasing, and the number of episodes complicated by infective endocarditis (IE)
      varies. Performing transesophageal echocardiography (TEE) in all patients with E
      BSI is costly and time-consuming. Our objectives were to identify patients with E
      BSI who are at very low risk of enterococcal IE (and therefore do not require
      TEE) and to compare the outcome of E-BSI in patients with/without IE. METHODS:
      Between September 2003 and October 2012, we performed a prospective cohort study
      (all patients with E-BSI) and a case-control study (patients with/without
      enterococcal IE) in our center. RESULTS: We detected 1515 patients with E-BSI and
      65 with enterococcal IE (4.29% of all episodes of E-BSI, 16.7% of patients with E
      BSI who underwent transthoracic echocardiography, and 35.5% of all patients with
      E-BSI who underwent TEE). We developed a bedside predictive score for
      enterococcal IE-Number of positive blood cultures, Origin of the bacteremia,
      previous Valve disease, Auscultation of heart murmur (NOVA) score-based on the
      following variables: Number of positive blood cultures (3/3 blood cultures or the
      majority if more than 3), 5 points; unknown Origin of bacteremia, 4 points; prior
      heart Valve disease, 2 points; Auscultation of a heart murmur, 1 point (receiver
      operating characteristic = 0.83). The best cutoff corresponded to a score >=4
      (sensitivity, 100%; specificity, 29%). A score <4 points suggested a very low
      risk for enterococcal IE and that TEE could be obviated. CONCLUSIONS:
      Enterococcal IE may be more frequent than generally thought. Depending on local
      prevalence of endocarditis, application of the NOVA score may safely obviate
      echocardiography in 14%-27% of patients with E-BSI.

PMID- 25381325
TI  - Cardiovascular outcomes in Fabry disease are linked to severity of chronic kidney
      disease.
AB  - OBJECTIVES: Assess the impact of end-stage renal disease (chronic kidney disease
      stage 5 (CKD5)) on cardiovascular outcomes in patients with Fabry disease on
      enzyme replacement therapy. BACKGROUND: Fabry disease, an X-linked lysosomal
      storage disease, causes hypertrophic cardiomyopathy and cardiovascular
      dysfunction. METHODS: Cardiac and renal function of 25 male patients with Fabry
      disease were analysed at 0, 1, 2, 5, 7 and 10 years after initiation of
      treatment. Patients were grouped at baseline into those with CKD5 (n=10) and
      those without (n=15). ECG and echocardiography were performed 6 and 12 monthly,
      respectively, while renal function was measured yearly. RESULTS: After 10 years
      of treatment, cardiac and renal function in non-CKD5 patients remained unchanged.
      In contrast, CKD5 was associated with worse baseline cardiac parameters and
      progressive LV hypertrophy. LV mass index grew by 35.4+/-31.8 g/m(2.7) in CKD5
      versus 5.7+/-7.9 g/m(2.7), p=0.044 in non-CKD5, predominantly due to increased
      interventricular septal wall thickness (7.7+/-5.5 mm vs 1.3+/-1.7 mm, p=0.003).
      Cardiovascular events, including sudden death, arrhythmia and pacing device
      insertion, occurred in 100% patients with CKD5 (21 events) and 26% non-CKD5
      patients (7 events), p<0.0001. Additionally, estimated LV filling pressure (E/Ea)
      was significantly higher in patients having cardiovascular events (21.1+/-7.7 vs
      12.5+/-4.5, p=0.008) irrespective of renal function. CONCLUSIONS: End-stage renal
      disease was the strongest indicator of cardiovascular disease progression in
      Fabry disease. Enzyme replacement initiated prior to CKD5 was associated with
      stability in cardiac and renal disease while patients with CKD5 showed ongoing
      deterioration. Additionally, E/Ea >=15 may predict risk of cardiac events.

PMID- 25381327
TI  - Echocardiographic findings in 2261 peri-pubertal athletes with or without
      inverted T waves at electrocardiogram.
AB  - OBJECTIVE: T wave inversion (TWI) has been associated with cardiomyopathies. The
      hypothesis of this study was that TWI has relevant clinical significance in peri
      pubertal athletes. METHODS: Consecutive male soccer players, aged 8-18 years,
      undergoing preparticipation screening between January 2008 and March 2009 were
      enrolled. Medical and family histories were collected; physical examinations, 12
      lead ECGs and transthoracic echocardiogram (TTE) were performed. TWI was
      categorised by ECG lead (anterior (V1-V3), extended anterior (V1-V4), inferior
      (DII-aVF) and infero-lateral (DII-aVF/V4-V6/DI-aVL)) and by age. RESULTS:
      Overall, 2261 (mean age 12.4 years, 100% Caucasian) athletes were enrolled. TWI
      in >=2 consecutive ECG leads was found in 136 athletes (6.0%), mostly in anterior
      leads (126/136, 92.6%). TWI in anterior leads was associated with TTE
      abnormalities in 6/126 (4.8%) athletes. TWI in extended anterior (2/136, 1.5%)
      and inferior (3/136, 2.2%) leads was never associated with abnormal TTE. TWI in
      infero-lateral leads (5/136, 3.7%) was associated with significant TTE
      abnormalities (3/5, 60.0%), including one hypertrophic cardiomyopathy (HCM) and
      two LV hypertrophies. Athletes with normal T waves had TTE abnormalities in 4.4%
      of cases, including one HCM with deep Q waves in infero-lateral leads.
      CONCLUSIONS: In this broad population of peri-pubertal male athletes, TWI in
      anterior leads was associated with mild cardiac disease in 4.8% of cases, while
      TWI in infero-lateral leads revealed HCM and LV hypertrophy in 60% of cases. ECG
      identified all cases of HCM.

PMID- 25381329
TI  - Acute pediatric musculoskeletal pain management in North America: a practice
      variation survey.
AB  - Children's musculoskeletal (MSK) injury pain remains poorly managed. This survey
      of pediatric emergency physicians and orthopedic surgeons assessed analgesia
      administration practices and discharge advice for children with acute MSK pain;
      683 responses were received. Ibuprofen was the most commonly reported analgesic
      used in the emergency department (52%) and at discharge (68%). Most (85%)
      reported using oral opioids in the previous 6 months. Codeine use was the most
      commonly reported opioid used in the emergency department (38%) and at home
      (51%). For equal levels of pain, younger children received less opioids than
      older children. Younger physicians and recent graduates chose acetaminophen and
      codeine more than older and more experienced colleagues, who preferred ibuprofen
      and non-codeine containing opioid compounds (P < .001 and .006, respectively).
      Orthopedic surgeons reported less ibuprofen use than pediatric emergency
      physicians (P < .001). Choice of analgesic agents is heterogeneous among
      physicians and is influenced by pain severity, child's age, and physician
      characteristics. 

PMID- 25381328
TI  - Natural antisense RNAs are involved in the regulation of CD45 expression in
      autoimmune diseases.
AB  - CD45 is a transmembrane protein tyrosine phosphatase that is specifically
      expressed in hematopoietic cells and can initiate signal transduction via the
      dephosphorylation of tyrosine. Alternatively spliced transcript variants of this
      gene encode distinct isoforms, which indicate different functional states of
      CD45. Among these variants, CD45RO, which contains neither exon 4, 5, or 6, is
      over-expressed in lymphocytes in autoimmune diseases, including systemic lupus
      erythematosus, rheumatoid arthritis, multiple sclerosis, and type I diabetes. The
      CD45 RO serves as a marker of the immune response activity and lymphocyte
      development. Previous studies have indicated that exon splicing is generally
      correlated with local hypermethylated DNA and acetylated histone modification,
      while autoimmune diseases are commonly associated with global hypomethylation and
      histone deacetylation in lymphocytes. Thus, the question arises of how exons 4,
      5, and 6 of CD45RO are excluded under the status of global DNA hypomethylation
      and histone deacetylation in these autoimmune diseases. On the basis of the
      analyses of the context sequence of CD45 and its natural antisense RNA in
      GenBank, we proposed that the long noncoding RNA encoded by the natural antisense
      gene of CD45 contributes to the expressional regulation of the CD45RO splicing
      variant via recruitment of DNA methyltransferase and histone modification
      modulators specific to the sense gene CD45; thus, it is associated with the over
      expression of CD45RO and the functional regulation of lymphocytes in the
      pathogenic development of autoimmune diseases. 

PMID- 25381330
TI  - Isolation of canine coronary sinus musculature from the atria by radiofrequency
      catheter ablation prevents induction of atrial fibrillation.
AB  - BACKGROUND: The junction between the coronary sinus (CS) musculature and both
      atria contributes to initiation of atrial tachyarrhythmias. The current study
      investigated the effects of CS isolation from the atria by radiofrequency
      catheter ablation on the induction and maintenance of atrial fibrillation (AF).
      METHODS AND RESULTS: Using an optical mapping system, we mapped action potentials
      at 256 surface sites in 17 isolated and arterially perfused canine atrial tissues
      containing the entire musculature of the CS, right atrial septum, posterior left
      atrium, left inferior pulmonary vein, and vein of Marshal. Rapid pacing from each
      site before and after addition of acetylcholine (0.5 MUmol/L) was applied to
      induce AF. Epicardial radiofrequency catheter ablation at CS-atrial junctions
      isolated the CS from the atria. Rapid pacing induced sustained AF in all tissues
      after acetylcholine. Microreentry within the CS drove AF in 88% of preparations.
      Reentries associated with the vein of Marshall (29%), CS-atrial junctions (53%),
      right atrium (65%), and pulmonary vein (76%) (frequently with 2-4 simultaneous
      circuits) were additional drivers of AF. Radiofrequency catheter ablation
      eliminated AF in 13 tissues before acetylcholine (P<0.01) and in 5 tissues after
      acetylcholine. Radiofrequency catheter ablation also abbreviated the duration of
      AF in 12 tissues (P<0.01). CONCLUSIONS: CS and its musculature developed unstable
      reentry and AF, which were prevented by isolation of CS musculature from atrial
      tissue. The results suggest that CS can be a substrate of recurrent AF in
      patients after pulmonary vein isolation and that CS isolation might help prevent
      recurrent AF.

PMID- 25381326
TI  - Heart failure risk prediction in the Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: Heart failure (HF) is a leading cause of mortality especially in older
      populations. Early detection of high-risk individuals is imperative for primary
      prevention. The purpose of this study was to develop a HF risk model from a
      population without clinical cardiac disease. METHODS: The Multi-Ethnic Study of
      Atherosclerosis is a multicentre observational cohort study following 6814
      subjects (mean age 62+/-10 years; 47% men) who were free of clinical
      cardiovascular disease at baseline. Median follow-up was 4.7 years. HF events
      developed in 176 participants. Cox proportional hazards models and regression
      coefficients were used to determine independent risk factors and generate a 5
      year risk score for incident HF. Bootstrapping with bias correction was used for
      internal validation. RESULTS: Independent predictors for HF (HR, p value) were
      age (1.30 (1.10 to 1.50) per 10 years), male gender (2.27 (1.53 to 3.36)),
      current smoking (1.97 (1.15 to 3.36)), body mass index (1.40 (1.10 to 1.80) per 5
      kg/m(2)), systolic blood pressure (1.10 (1.00 to 1.10) per 10 mm Hg), heart rate
      (1.30) (1.10 to 1.40) per 10 bpm), diabetes (2.27 (1.48 to 3.47)), N-terminal pro
      B-type natriuretic peptide (NT proBNP) (2.48 (2.16 to 2.84) per unit log
      increment) and left ventricular mass index (1.40 (1.30 to 1.40) per 10 g/m(2)). A
      parsimonious model based on age, gender, body mass index, smoking status,
      systolic blood pressure, heart rate, diabetes and NT proBNP natriuretic peptide
      predicted incident HF risk with a c-statistic of 0.87. CONCLUSIONS: A clinical
      algorithm based on risk factors readily available in the primary care setting can
      used to identify individuals with high likelihood of developing HF without pre
      existing cardiac disease.

PMID- 25381331
TI  - Relationship between catheter contact force and radiofrequency lesion size and
      incidence of steam pop in the beating canine heart: electrogram amplitude,
      impedance, and electrode temperature are poor predictors of electrode-tissue
      contact force and lesion size.
AB  - BACKGROUND: Electrode-tissue contact force (CF) is believed to be a major factor
      in radiofrequency lesion size. The purpose of this study was to determine, in the
      beating canine heart, the relationship between CF and radiofrequency lesion size
      and the accuracy of predicting CF and lesion size by measuring electrogram
      amplitude, impedance, and electrode temperature. METHODS AND RESULTS: Eight dogs
      were studied closed chest. Using a 7F catheter with a 3.5 mm irrigated electrode
      and CF sensor (TactiCath, St. Jude Medical), radiofrequency applications were
      delivered to 3 separate sites in the right ventricle (30 W, 60 seconds, 17 mL/min
      irrigation) and 3 sites in the left ventricle (40 W, 60 seconds, 30 mL/min
      irrigation) at (1) low CF (median 8 g); (2) moderate CF (median 21 g); and (3)
      high CF (median 60 g). Dogs were euthanized and lesion size was measured. At
      constant radiofrequency and time, lesion size increased significantly with
      increasing CF (P<0.01). The incidence of a steam pop increased with both
      increasing CF and higher power. Peak electrode temperature correlated poorly with
      lesion size. The decrease in impedance during the radiofrequency application
      correlated well with lesion size for lesions in the left ventricle but less well
      for lesions in the right ventricle. There was a poor relationship between CF and
      the amplitude of the bipolar or unipolar ventricular electrogram, unipolar injury
      current, and impedance. CONCLUSIONS: Radiofrequencylesion size and the incidence
      of steam pop increase strikingly with increasing CF. Electrogram parameters and
      initial impedance are poor predictors of CF for radiofrequency ablation.

PMID- 25381332
TI  - Prevalence and prognostic significance of abnormal P terminal force in lead V1 of
      the ECG in the general population.
AB  - BACKGROUND: Prevalence and prognostic significance of abnormal P terminal force
      (PTF) in the general population are not known. The aim of this study was to
      assess the prevalence of abnormal PTF and to compare clinical outcomes of middle
      aged subjects with and without the PTF. METHODS AND RESULTS: The presence of PTF
      was assessed in a cohort of 10 647 middle-aged subjects (mean age [SD], 44 [8]
      years; 47.2% female). The subjects were followed 35 to 41 years, and data on
      mortality and hospitalizations were obtained from national registers. Primary
      outcomes were all-cause mortality, cardiac mortality, and arrhythmic death.
      Secondary outcomes were hospitalization because of congestive heart failure,
      coronary heart disease, new onset atrial fibrillation, and stroke. The Cox
      proportional hazards model was used to assess the risk for death (all-cause), and
      the Fine and Gray competing risks model was used for other outcomes. The
      prevalence of PTF 0.04 to 0.049, 0.05 to 0.059, and >=0.06 mm.s were 4.8%, 1.5%,
      and 1.2%, respectively. Subjects presenting PTF >=0.04 mm.s were at increased
      risk for death, cardiac death, and congestive heart failure, and subjects
      presenting PTF >=0.06 mm.s were at increased risk for atrial fibrillation.
      However, after adjustment for potential confounding factors, an increased risk
      was observed only for death (hazard ratio, 1.76; 95% confidence interval, 1.45
      2.12; P<0.001) and atrial fibrillation (hazard ratio, 1.91; 95% confidence
      interval, 1.34-2.73; P<0.001) in subjects presenting PTF >=0.06 mm.s.
      CONCLUSIONS: PTF >=0.04 mm.s is a relatively common finding in a 12-lead ECG of
      middle-aged subjects. PTF >=0.06 mm.s is associated with increased risk for
      atrial fibrillation and death in the general population.

PMID- 25381333
TI  - Functional characterization of CYP2D6 enhancer polymorphisms.
AB  - CYP2D6 metabolizes nearly 25% of clinically used drugs. Genetic polymorphisms
      cause large inter-individual variability in CYP2D6 enzyme activity and are
      currently used as biomarker to predict CYP2D6 metabolizer phenotype. Previously,
      we had identified a region 115 kb downstream of CYP2D6 as enhancer for CYP2D6,
      containing two completely linked single nucleotide polymorphisms (SNPs), rs133333
      and rs5758550, associated with enhanced transcription. However, the enhancer
      effect on CYP2D6 expression, and the causative variant, remained to be
      ascertained. To characterize the CYP2D6 enhancer element, we applied chromatin
      conformation capture combined with the next-generation sequencing (4C assays) and
      chromatin immunoprecipitation with P300 antibody, in HepG2 and human primary
      culture hepatocytes. The results confirmed the role of the previously identified
      enhancer region in CYP2D6 expression, expanding the number of candidate variants
      to three highly linked SNPs (rs133333, rs5758550 and rs4822082). Among these,
      only rs5758550 demonstrated regulating enhancer activity in a reporter gene
      assay. Use of clustered regularly interspaced short palindromic repeats mediated
      genome editing in HepG2 cells targeting suspected enhancer regions decreased
      CYP2D6 mRNA expression by 70%, only upon deletion of the rs5758550 region. These
      results demonstrate robust effects of both the enhancer element and SNP rs5758550
      on CYP2D6 expression, supporting consideration of rs5758550 for CYP2D6 genotyping
      panels to yield more accurate phenotype prediction. 

PMID- 25381334
TI  - Landscape of DNA methylation on the X chromosome reflects CpG density, functional
      chromatin state and X-chromosome inactivation.
AB  - X-chromosome inactivation (XCI) achieves dosage compensation between males and
      females through the silencing of the majority of genes on one of the female X
      chromosomes. Thus, the female X chromosomes provide a unique opportunity to study
      euchromatin and heterochromatin of allelic regions within the same nuclear
      environment. We examined the interplay of DNA methylation (DNAm) with CpG
      density, transcriptional activity and chromatin state at genes on the X
      chromosome using over 1800 female samples analysed with the Illumina Infinium
      Human Methylation450 BeadChip. DNAm was used to predict an inactivation status
      for 63 novel transcription start sites (TSSs) across 27 tissues. There was high
      concordance of inactivation status across tissues, with 62% of TSSs subject to
      XCI in all 27 tissues examined, whereas 9% escaped from XCI in all tissues, and
      the remainder showed variable escape from XCI between females in subsets of
      tissues. Inter-female and twin data supported a model of predominately cis-acting
      influences on inactivation status. The level of expression from the inactive X
      relative to the active X correlated with the amount of female promoter DNAm to a
      threshold of ~30%, beyond which genes were consistently subject to inactivation.
      The inactive X showed lower DNAm than the active X at intragenic and intergenic
      regions for genes subject to XCI, but not at genes that escape from inactivation.
      Our categorization of genes that escape from X inactivation provides candidates
      for sex-specific differences in disease. 

PMID- 25381335
TI  - Safety and efficacy of cardiac rehabilitation for patients with continuous flow
      left ventricular assist devices.
AB  - BACKGROUND: Despite the increasing use of left ventricular assist devices (LVADs)
      in terminal heart failure, cardiac rehabilitation protocols have not yet been
      documented in larger LVAD patient cohorts. The aim of this study was to
      investigate safety and efficacy of exercise training during a rehabilitation
      programme after post-operative discharge of LVAD patients. METHODS:
      Rehabilitation data obtained between 2010-2012 from 41 LVAD patients (mean age
      54.8 +/- 11.6 years; 20% female) were retrospectively analysed. The exercise
      protocol consisted of strength exercises for lower limbs, bicycle ergometry,
      walking and gymnastics. The numbers of training sessions, their duration and
      intensity as well as adverse events were documented. Spiroergometry was performed
      at least once and twice in a subgroup of 15 patients (at the beginning and end of
      rehabilitation). RESULTS: Rehabilitation started 48 +/- 38 days post LVAD
      implantation with an average duration of 32 +/- 6 days. An increase in exercise
      capacity was observed. Duration (19 +/- 4 vs 14 +/- 2 min, p < 0.001) and
      intensity of bicycle ergometry increased (module number 6.2 +/- 2.8 vs 2.0 +/-
      1.9, p < 0.001) as well as muscular strength all muscle groups trained (e.g. 33.6
      +/- 15.2 vs 26.6 +/- 11.9 kg at the leg press, p = 0.002). Spiroergometry
      revealed an increase of maximal oxygen consumption (14.5 +/- 5.2 vs 11.3 +/- 4.1
      ml/min/kg, p = 0.007) in the subgroup that underwent two examinations. In the
      whole population the average increase was lower (12.81 +/- 4.35 ml/min/kg). One
      training-related adverse event (non-sustained ventricular tachycardia) was
      observed. CONCLUSION: Exercise training for LVAD patient as part of a
      multidisciplinary rehabilitation programme is effective and safe. This warrants
      the broad application of exercise training after LVAD implantation.

PMID- 25381336
TI  - Lipid accumulation product and incident cardiovascular events in a normal weight
      population: Tehran Lipid and Glucose Study.
AB  - BACKGROUND: The lipid accumulation product (LAP) is a relatively new marker for
      measuring cardiovascular disease (CVD) risk factors. We investigated
      predictability of LAP value for incident CVD among Tehranian adults with normal
      BMI. METHODS: A population based cohort of subjects without history of prevalent
      cardiovascular disease, aged >=30 years who had BMI <25 were followed for a
      median (interquartile range 25-75) of 10.1 (7.25-10.57) years. Subjects were
      stratified according to LAP tertiles. LAP was defined as WC-58 * TG for women and
      WC-65 * TG for men (where WC is waist circumference and TG is triglycerides). Cox
      regression analyses were used to estimate the hazard ratio (HR) of CVD events; c
      statistics test was also calculated to compare LAP with other anthropometric
      indices. RESULT: In this prospective study of 2378 subjects (57.0% men) with mean
      age of 46.1 +/- 13.5 years, and mean BMI 22.59 +/- 1.9 kg/m(2) an increasing
      trend of cardiovascular risk factors along LAP tertiles (except for smoking and
      history of premature CVD events) was observed. During follow-up 160 CVD cases
      occurred (incidence rates (per 1000 person-years) of CVD across LAP tertiles were
      4.14 (2.88-5.96), 6.82 (5.13-9.04) and 12.37 (9.97-15.34), respectively).
      Adjusted HRs for development of cardiovascular disease across LAP tertiles were
      1.56 (95% confidence interval (CI) =0.91-2.69) and 2.17 (95% CI = 1.22-3.86)
      respectively. C-statistics of LAP were not significantly higher than other
      anthropometric measures for predicting incident CVD. CONCLUSION: LAP is an
      independent predictor of cardiovascular events in normal BMI subjects, but is not
      superior over other anthropometrics indices.

PMID- 25381337
TI  - Cardiopulmonary fitness is a function of lean mass, not total body weight: The
      DR's EXTRA study.
AB  - BACKGROUND: Division by total body weight is the usual way to standardise peak
      oxygen uptake (peak VO2) for body size. However, this method systematically
      underestimates cardiopulmonary fitness in obese individuals. Our aim was to
      analyse whether lean-mass is a better base for a body mass-independent standard
      of cardiopulmonary fitness. METHODS: A population based sample of 578 men (body
      mass index (BMI) 19-47 kg/m(2)) and 592 women (BMI 16-49 kg/m(2)) 57-78 years of
      age. Peak VO2 was assessed by respiratory gas analysis during a maximal exercise
      test on a cycle ergometer. We studied the validity of the weight-ratio and the
      lean mass-ratio standards in a linear regression model. RESULTS: The weight-ratio
      standard implies an increase of peak VO2 per additional kg body weight with 20.7
      ml/min (95% confidence interval (CI): 20.3-21.1) in women and 26.9 ml/min (95%
      CI: 26.4-27.5) in men. The observed increase per kg is only 8.5 ml/min (95% CI:
      6.5-10.5) in men and 10.4 ml/min (95% CI: 7.5-13.4) in women. For the lean mass
      ratio standard expected and observed increases in peak VO2 per kg lean mass were
      32.3 (95% CI: 31.8-32.9) and 34.6 (95% CI: 30.0-39.1) ml/min for women and 36.2
      (95% CI: 35.6-36.8) and 37.3 (95% CI: 32.1-42.4) ml/min in men. The lean mass
      ratio standard is a body mass-independent measure of cardiopulmonary fitness in
      100% of women and 58% of men; corresponding values for the weight-ratio standard
      were 11% and 16%. CONCLUSIONS: For comparisons of cardiopulmonary fitness across
      different categories of body mass, the lean mass-ratio standard should be used.

PMID- 25381338
TI  - Development of circulating tumor cell-endocrine therapy index in patients with
      hormone receptor-positive breast cancer.
AB  - BACKGROUND: Endocrine therapy (ET) fails to induce a response in one half of
      patients with hormone receptor (HR)-positive metastatic breast cancer (MBC), and
      almost all will eventually become refractory to ET. Circulating tumor cells (CTC)
      are associated with worse prognosis in patients with MBC, but enumeration alone
      is insufficient to predict the absolute odds of benefit from any therapy,
      including ET. We developed a multiparameter CTC-Endocrine Therapy Index (CTC
      ETI), which we hypothesize may predict resistance to ET in patients with HR
      positive MBC. METHODS: The CTC-ETI combines enumeration and CTC expression of
      four markers: estrogen receptor (ER), B-cell lymphoma 2 (BCL-2), Human Epidermal
      Growth Factor Receptor 2 (HER2), and Ki67. The CellSearch System and reagents
      were used to capture CTC and measure protein expression by immunofluorescent
      staining on CTC. RESULTS: The feasibility of determining CTC-ETI was initially
      established in vitro and then in a prospective single-institution pilot study in
      patients with MBC. CTC-ETI was successfully determined in 44 of 50 (88%)
      patients. Eighteen (41%), 9 (20%), and 17 (39%) patients had low, intermediate,
      and high CTC-ETI scores, respectively. Interobserver concordance of CTC-ETI
      determination was from 94% to 95% (Kappa statistic, 0.90-0.91). Inter- and cell
      to-cell intrapatient heterogeneity of expression of each of the CTC markers was
      observed. CTC biomarker expression was discordant from both primary and
      metastatic tissues. CONCLUSIONS: CTC expression of ER, BCL-2, HER2, and Ki67 can
      be reproducibly measured with high analytical validity using the CellSearch
      System. The clinical implications of CTC-ETI, and of the heterogeneity of CTC
      biomarker expression, are being evaluated in an ongoing prospective trial.

PMID- 25381340
TI  - Urinary creatinine and survival in CKD.

PMID- 25381339
TI  - 18F-FAZA PET imaging response tracks the reoxygenation of tumors in mice upon
      treatment with the mitochondrial complex I inhibitor BAY 87-2243.
AB  - PURPOSE: We describe a noninvasive PET imaging method that monitors early
      therapeutic efficacy of BAY 87-2243, a novel small-molecule inhibitor of
      mitochondrial complex I as a function of hypoxia-inducible factor-1alpha
      (HIF1alpha) activity. EXPERIMENTAL DESIGN: Four PET tracers [(18)F-FDG, (18)F
      Fpp(RGD)2, (18)F-FLT, and (18)F-FAZA] were assessed for uptake into tumor
      xenografts of drug-responsive (H460, PC3) or drug-resistant (786-0) carcinoma
      cells. Mice were treated with BAY 87-2243 or vehicle. At each point, RNA from
      treated and vehicle H460 tumor xenografts (n = 3 each) was isolated and analyzed
      for target genes. RESULTS: Significant changes in uptake of (18)F-FAZA, (18)F
      FLT, and (18)F-Fpp(RGD)2 (P < 0.01) occurred with BAY 87-2243 treatment with
      (18)F-FAZA being the most prominent. (18)F-FDG uptake was unaffected. (18)F-FAZA
      tumor uptake declined by 55% to 70% (1.21% +/- 0.10%ID/g to 0.35 +/- 0.1%ID/g; n
      = 6, vehicle vs. treatment) in both H460 (P < 0.001) and PC3 (P < 0.05)
      xenografts 1 to 3 days after drug administration. (18)F-FAZA uptake in 786-0
      xenografts was unaffected. Decline occurred before significant differences in
      tumor volume, thus suggesting (18)F-FAZA decrease reflected early changes in
      tumor metabolism. BAY 87-2243 reduced expression of hypoxia-regulated genes CA
      IX, ANGPTL4, and EGLN-3 by 99%, 93%, and 83%, respectively (P < 0.001 for all),
      which corresponds with reduced (18)F-FAZA uptake upon drug treatment.
      Heterogeneous expression of genes associated with glucose metabolism, vessel
      density, and proliferation was observed. CONCLUSIONS: Our studies suggest
      suitability of (18)F-FAZA-PET as an early pharmacodynamic monitor on the efficacy
      of anticancer agents that target the mitochondrial complex I and intratumor
      oxygen levels (e.g., BAY 87-2243).

PMID- 25381341
TI  - Association of serum bicarbonate with incident functional limitation in older
      adults.
AB  - BACKGROUND AND OBJECTIVES: Cross-sectional studies have found that low serum
      bicarbonate is associated with slower gait speed. Whether bicarbonate levels
      independently predict the development of functional limitation has not been
      previously studied. Whether bicarbonate was associated with incident persistent
      lower extremity functional limitation and whether the relationship differed in
      individuals with and without CKD were assessed in participants in the Health,
      Aging, and Body Composition study, a prospective study of well functioning older
      individuals DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Functional limitation
      was defined as difficulty in walking 0.25 miles or up 10 stairs on two
      consecutive reports 6 months apart in the same activity (stairs or walking).
      Kidney function was measured using eGFR by the Chronic Kidney Disease
      Epidemiology Collaboration creatinine equation, and CKD was defined as an eGFR<60
      ml/min per 1.73 m(2). Serum bicarbonate was measured using arterialized venous
      blood gas. Cox proportional hazards analysis was used to assess the association
      of bicarbonate (<23, 23-25.9, and >=26 mEq/L) with functional limitation. Mixed
      model linear regression was performed to assess the association of serum
      bicarbonate on change in gait speed over time. RESULTS: Of 1544 participants, 412
      participants developed incident persistent functional limitation events over a
      median 4.4 years (interquartile range, 3.1 to 4.5). Compared with >=26 mEq/L,
      lower serum bicarbonate was associated with functional limitation. After
      adjustment for demographics, CKD, diabetes, body mass index, smoking, diuretic
      use, and gait speed, lower serum bicarbonate was significantly associated with
      functional limitation (hazard ratio, 1.35; 95% confidence interval, 1.08 to 1.68
      and hazard ratio, 1.58; 95% confidence interval, 1.12 to 2.22 for bicarbonate
      levels from 23 to 25.9 and <23, respectively). There was not a significant
      interaction of bicarbonate with CKD. In addition, bicarbonate was not
      significantly associated with change in gait speed. CONCLUSIONS: Lower serum
      bicarbonate was associated with greater risk of incident, persistent functional
      limitation. This association was present in individuals with and without CKD.

PMID- 25381343
TI  - Acid-base balance and physical function.

PMID- 25381342
TI  - Urinary creatinine excretion, bioelectrical impedance analysis, and clinical
      outcomes in patients with CKD: the CRIC study.
AB  - BACKGROUND AND OBJECTIVES: Previous studies in chronic disease states have
      demonstrated an association between lower urinary creatinine excretion (UCr) and
      increased mortality, a finding presumed to reflect the effect of low muscle mass
      on clinical outcomes. Little is known about the relationship between UCr and
      other measures of body composition in terms of the ability to predict outcomes of
      interest. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the
      Chronic Renal Insufficiency Cohort (CRIC), the relationship between UCr, fat free
      mass (FFM) as estimated by bioelectrical impedance analysis, and (in a
      subpopulation) whole-body dual-energy x-ray absorptiometry assessment of
      appendicular lean mass were characterized. The associations of UCr and FFM with
      mortality and ESRD were compared using Cox proportional hazards models. RESULTS:
      A total of 3604 CRIC participants (91% of the full CRIC cohort) with both a
      baseline UCr and FFM measurement were included; of these, 232 had contemporaneous
      dual-energy x-ray absorptiometry measurements. Participants were recruited
      between July 2003 and March 2007. UCr and FFM were modestly correlated (rho=0.50;
      P<0.001), while FFM and appendicular lean mass were highly correlated (rho=0.91;
      P<0.001). Higher urinary urea nitrogen, black race, younger age, and lower serum
      cystatin C level were all significantly associated with higher UCr. Over a median
      (interquartile range) of 4.2 (3.1-5.0) years of follow-up, 336 (9.3%)
      participants died and 510 (14.2%) reached ESRD. Lower UCr was associated with
      death and ESRD even after adjustment for FFM (adjusted hazard ratio for death per
      1 SD higher level of UCr, 0.63 [95% confidence interval, 0.56 to 0.72]; adjusted
      hazard ratio for ESRD per 1 SD higher level of UCr, 0.70 [95% confidence
      interval, 0.63 to 0.75]). CONCLUSIONS: Among a cohort of individuals with CKD,
      lower UCr is associated with death and ESRD independent of FFM as assessed by
      bioelectrical impedance analysis.

PMID- 25381344
TI  - Cortical vs. afferent stimulation as an adjunct to functional task practice
      training: a randomized, comparative pilot study in people with cervical spinal
      cord injury.
AB  - OBJECTIVE: To assess single-session effects of three different types of stimuli
      known to increase cortical excitability when combined with functional task
      practice. DESIGN: Randomized cross-over trial. PARTICIPANTS: A total of 24
      participants with chronic cervical spinal cord injury. INTERVENTIONS: One 30
      minute session of each, applied concurrently with functional task practice:
      transcranial direct current stimulation, vibration, and transcutaneous electrical
      nerve stimulation. MEASUREMENTS: Nine-hole Peg Test, pinch force, visuomotor
      tracking, and cortical excitability were collected at pretest, posttest and late
      posttest (30 minutes after). Early effects (posttest minus pretest) and short
      term persistence (late posttest minus pretest) were assessed using a general
      linear mixed model. Magnitude of effect size was assessed using the Cohen's d.
      RESULTS: Transcutaneous electrical nerve stimulation was associated with
      moderate, significant early effects and short-term persistence on Nine-hole Peg
      Test performance (1.8 +/-1.8, p = 0.003, d = 0.59; 2.0 +/-2.5, p < 0.001, Cohen's
      d = 0.65, respectively). Transcranial direct current stimulation (1.8 +/-2.5, p =
      0.003, Cohen's d = 0.52) was also associated with significant short-term
      persistence of moderate size on Nine-hole Peg Test performance (1.8 +/-2.5, p =
      0.003, Cohen's d = 0.52) and visuomotor tracking performance (p = 0.05, d =
      0.51). Early effects on corticomotor excitability were significant for
      transcutaneous electrical nerve stimulation (p = 0.003), approached significance
      for transcranial direct current stimulation (p = 0.07), and only vibration was
      associated with significant short-term persistence (p = 0.006). CONCLUSIONS:
      Meaningful improvements in aspects of hand-related function that persisted at
      least 30 minutes after intervention were observed with transcutaneous electrical
      nerve stimulation and transcranial direct current stimulation, when combined with
      functional task practice.

PMID- 25381345
TI  - Comparison of occupation-based and impairment-based occupational therapy for
      subacute stroke: a randomized controlled feasibility study.
AB  - OBJECTIVE: To compare occupation-based and impairment-based approaches in
      occupational therapy and determine the feasibility of patient recruitment and
      retention. DESIGN: A multicenter, randomized, controlled pilot trial with a
      single blind assessor. SETTING: Ten subacute rehabilitation units in Japan.
      PARTICIPANTS: Fifty-four patients with subacute stroke. INTERVENTIONS: The
      experimental group used the iPad application, Aid for Decision-making in
      Occupation Choice, to establish occupation-based goals, and evaluation and
      intervention were conducted mainly through real occupations. The control group
      was evaluated according to patients' generic abilities and activities of daily
      living (ADL), and the intervention mainly involved the impairment-based approach.
      MAIN OUTCOME MEASURES: Short Form-36, Functional Independence Measure, Brunnstrom
      recovery stages, The Client Satisfaction Questionnaire, and length of hospital
      stay. RESULTS: Of the 1465 potential participants, 54 (3%) subacute stroke
      patients were enrolled over 16 months and 68% (n = 36) were retained to the 2
      month assessment: experimental group (n = 16); control group (n = 21). Although
      there was no significant intergroup difference for any outcomes, the experimental
      group had a small effect size advantage on the Short Form-36 "General health" (d
      = 0.42) and "Role emotional" (d = 0.43) subscales relative to the control group.
      A sample of 118 subacute stroke patients per group would be required for a lager
      study. CONCLUSIONS: Results suggest that the occupation-based approach has more
      potential to improve "General health" and "Role emotional" scores on the Short
      Form-36 than the impairment-based approach. Further investigation of study
      protocol with interventions and recruiting is needed prior to a larger trial.

PMID- 25381346
TI  - Can we forget the Mini-Mental State Examination? A systematic review of the
      validity of cognitive screening instruments within one month after stroke.
AB  - OBJECTIVE: To review systematically studies investigating the convergent,
      criterion, and predictive validity of multi-domain cognitive screening
      instruments in the first four weeks after stroke. DATA SOURCES: Electronic
      databases (Pubmed, PsycINFO, CINAHL, Embase) were searched until June 2014.
      REVIEW METHODS: Studies concerning screening for cognitive dysfunction in stroke
      patients using multi-domain instruments, within four weeks postinfarct or
      haemorrhagic stroke, using tests taking no longer than one hour. Convergent,
      criterion, and predictive validity were examined. RESULTS: A total of 51 studies
      investigating 16 cognitive screening instruments were identified. None of the
      instruments covered all of the most affected cognitive domains. Only one study
      investigated the convergent validity of a multi-domain test during the (sub)acute
      phase after stroke. A total of 15 studies examined the criterion validity of
      cognitive measurements during the acute phase after stroke. The Montreal
      Cognitive Assessment and Higher Cortical Function Deficit Test had good criterion
      validity. A total of 24 studies examined the predictive ability of multi-domain
      cognitive instruments applied in the acute phase after stroke. The Cognistat,
      Montreal Cognitive Assessment, and Functional Independence Measure-cognitive
      showed good predictive validity. The Mini-Mental State Examination is the most
      widely used cognitive screening instrument, but shows insufficient criterion
      validity. CONCLUSION: None of the existing instruments fulfils all criteria. The
      Montreal Cognitive Assessment is the best candidate at present, provided items
      measuring speed of information processing are added, and further studies
      investigating the optimal cut-offs are conducted.

PMID- 25381347
TI  - A multicentre study of intentional behavioural responses measured using the Coma
      Recovery Scale-Revised in patients with minimally conscious state.
AB  - OBJECTIVE: To investigate which conscious behaviour is most frequently detected
      using the Coma Recovery Scale-Revised in patients with minimally conscious state.
      DESIGN: Multicentre, cross-sectional study. SETTING: One intensive care unit, 8
      post-acute rehabilitation centres and 2 long-term facilities. SUBJECTS: Fifty-two
      patients with established diagnosis of minimally conscious state of different
      aetiology. MAIN MEASURES: All patients were assessed by the Coma Recovery Scale
      Revised. RESULTS: In most patients (34/52) non-reflexive responses were
      identified by two or more subscales of the Coma Recovery Scale-Revised, whereas
      in 14 patients only the visual subscale could identify cortically-mediated
      behaviours, and in the remaining 4 patients only the motor subscale did so.The
      clinical signs of intentional behaviour were most often detected by the visual
      subscale (43/52 patients) and by the motor subscale (31/52), and least frequently
      by the oromotor/verbal subscale (3/52) of the Coma Recovery Scale-Revised. This
      clinical pattern was observed independently from time post-onset and aetiology.
      CONCLUSIONS: Non-reflexive visual behaviour, identified by the visual subscale of
      Coma Recovery Scale-Revised, is the most frequently detected intentional sign
      consistent with the diagnosis of minimally conscious state, independently from
      aetiology and time post-onset.

PMID- 25381348
TI  - Effect of surgical decompression of nerves in the lower extremity in patients
      with painful diabetic polyneuropathy on stability: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of decompression of nerves in the lower
      extremity in patients with painful diabetic polyneuropathy on static balance
      using a sensitive pressure mat system. DESIGN: Non-blinded randomized controlled
      trial. SETTING: Single center study performed at the University Medical Center
      Utrecht between 2010-2013. SUBJECTS: Patients with painful diabetic
      polyneuropathy assessed with the Diabetic Neuropathy Symptom score and Diabetic
      Neuropathy Examination between 18-90 years. Exclusion criteria were: physical
      problems leading to instability, BMI>35 kg/m2, ankle fractures in history,
      amputations proximal to the tarsometatarsal joints, active foot ulcer(s), severe
      occlusive peripheral vascular diseases. INTERVENTION: Unilateral surgical nerve
      decompression at four sites in the lower extremity, the contralateral limb was
      used as control (within-patient comparison), with one year follow-up. MAIN
      MEASURES: Preoperatively and 6 and 12 months postoperatively, weight bearing and
      five variables of sway of the center of pressure were measured with a pressure
      mat with eyes open and eyes closed. T-test was used for evaluation of
      postoperative results. RESULTS: Thirty-nine Patients met inclusion criteria and
      were enrolled for stability testing. Postoperatively no significant differences
      for sway variables and weight bearing were seen compared to preoperatively
      measurements. CONCLUSIONS: There is no evidence that surgical decompression of
      nerves of the lower extremity influences stability within one year after surgery
      in patients with painful diabetic polyneuropathy.

PMID- 25381349
TI  - Arterial elasticity in obese adolescents with clinical features of insulin
      resistance.
AB  - OBJECTIVE: To determine whether arterial elasticity differs between obese
      adolescents with clinical insulin resistance (IR), type 1 diabetes (T1D) and
      healthy non-obese controls. METHODS: This cross-sectional study evaluated 69
      adolescents with clinical IR, 91 with T1D and 63 age-matched (10- to 18-year-old)
      controls. Arterial elasticity was measured using radial tonometry pulse-wave
      analysis. Stepwise multiple regression analyses were performed to assess the
      determinants of the small and large arterial elasticity indices (SAEI and LAEI).
      RESULTS: SAEI and LAEI raw values were higher in the IR group than the controls,
      and these did not differ between the T1D and control groups. Weight and diastolic
      blood pressure (DBP) were significant predictors of SAEI. After adjustment for
      weight and DBP, SAEI decreased by 0.65 mL/mmHg * 100 for each 1-year increase in
      age in the IR group. SAEI was not different across the groups after controlling
      for weight and DBP. Height was the strongest predictor of LAEI which remained
      higher in the IR group after controlling for height and blood pressure.
      CONCLUSION: Obese adolescents with clinical IR have a higher SAEI, which declines
      with age; this may reflect a pathway to an increased risk of premature
      cardiovascular disease.

PMID- 25381350
TI  - Alternative acetate production pathways in Chlamydomonas reinhardtii during dark
      anoxia and the dominant role of chloroplasts in fermentative acetate production.
AB  - Chlamydomonas reinhardtii insertion mutants disrupted for genes encoding acetate
      kinases (EC 2.7.2.1) (ACK1 and ACK2) and a phosphate acetyltransferase (EC
      2.3.1.8) (PAT2, but not PAT1) were isolated to characterize fermentative acetate
      production. ACK1 and PAT2 were localized to chloroplasts, while ACK2 and PAT1
      were shown to be in mitochondria. Characterization of the mutants showed that
      PAT2 and ACK1 activity in chloroplasts plays a dominant role (relative to ACK2
      and PAT1 in mitochondria) in producing acetate under dark, anoxic conditions and,
      surprisingly, also suggested that Chlamydomonas has other pathways that generate
      acetate in the absence of ACK activity. We identified a number of proteins
      associated with alternative pathways for acetate production that are encoded on
      the Chlamydomonas genome. Furthermore, we observed that only modest alterations
      in the accumulation of fermentative products occurred in the ack1, ack2, and ack1
      ack2 mutants, which contrasts with the substantial metabolite alterations
      described in strains devoid of other key fermentation enzymes. 

PMID- 25381353
TI  - Hexokinase 1 and retinitis pigmentosa: insights into the retina and the molecule.

PMID- 25381351
TI  - Ectopic lignification in the flax lignified bast fiber1 mutant stem is associated
      with tissue-specific modifications in gene expression and cell wall composition.
AB  - Histochemical screening of a flax ethyl methanesulfonate population led to the
      identification of 93 independent M2 mutant families showing ectopic lignification
      in the secondary cell wall of stem bast fibers. We named this core collection the
      Linum usitatissimum (flax) lbf mutants for lignified bast fibers and believe that
      this population represents a novel biological resource for investigating how bast
      fiber plants regulate lignin biosynthesis. As a proof of concept, we
      characterized the lbf1 mutant and showed that the lignin content increased by
      350% in outer stem tissues containing bast fibers but was unchanged in inner stem
      tissues containing xylem. Chemical and NMR analyses indicated that bast fiber
      ectopic lignin was highly condensed and rich in G-units. Liquid chromatography
      mass spectrometry profiling showed large modifications in the oligolignol pool of
      lbf1 inner- and outer-stem tissues that could be related to ectopic
      lignification. Immunological and chemical analyses revealed that lbf1 mutants
      also showed changes to other cell wall polymers. Whole-genome transcriptomics
      suggested that ectopic lignification of flax bast fibers could be caused by
      increased transcript accumulation of (1) the cinnamoyl-CoA reductase, cinnamyl
      alcohol dehydrogenase, and caffeic acid O-methyltransferase monolignol
      biosynthesis genes, (2) several lignin-associated peroxidase genes, and (3) genes
      coding for respiratory burst oxidase homolog NADPH-oxidases necessary to increase
      H2O2 supply. 

PMID- 25381352
TI  - ULTRAPETALA trxG genes interact with KANADI transcription factor genes to
      regulate Arabidopsis gynoecium patterning.
AB  - Organ formation relies upon precise patterns of gene expression that are under
      tight spatial and temporal regulation. Transcription patterns are specified by
      several cellular processes during development, including chromatin remodeling,
      but little is known about how chromatin-remodeling factors contribute to plant
      organogenesis. We demonstrate that the trithorax group (trxG) gene ULTRAPETALA1
      (ULT1) and the GARP transcription factor gene KANADI1 (KAN1) organize the
      Arabidopsis thaliana gynoecium along two distinct polarity axes. We show that
      ULT1 activity is required for the kan1 adaxialized polarity defect, indicating
      that ULT1 and KAN1 act oppositely to regulate the adaxial-abaxial axis.
      Conversely, ULT1 and KAN1 together establish apical-basal polarity by promoting
      basal cell fate in the gynoecium, restricting the expression domain of the basic
      helix-loop-helix transcription factor gene SPATULA. Finally, we show that ult
      alleles display dose-dependent genetic interactions with kan alleles and that ULT
      and KAN proteins can associate physically. Our findings identify a dual role for
      plant trxG factors in organ patterning, with ULT1 and KAN1 acting
      antagonistically to pattern the adaxial-abaxial polarity axis but jointly to
      pattern the apical-basal axis. Our data indicate that the ULT proteins function
      to link chromatin-remodeling factors with DNA binding transcription factors to
      regulate target gene expression. 

PMID- 25381354
TI  - Comment on "Thiamine deficiency promotes T cell infiltration in experimental
      autoimmune encephalomyelitis: the involvement of CCL2".

PMID- 25381355
TI  - Response to Comment on "Thiamine deficiency promotes T cell infiltration in
      experimental autoimmune encephalomyelitis: the involvement of CCL2".

PMID- 25381356
TI  - General parity between trio and pairwise breeding of laboratory mice in static
      caging.
AB  - Changes made in the 8th edition of the Guide for the Care and Use of Laboratory
      Animals included new recommendations for the amount of space for breeding female
      mice. Adopting the new recommendations required, in essence, the elimination of
      trio breeding practices for all institutions. Both public opinion and published
      data did not readily support the new recommendations. In response, the National
      Jewish Health Institutional Animal Care and Use Committee established a program
      to directly compare the effects of breeding format on mouse pup survival and
      growth. Our study showed an overall parity between trio and pairwise breeding
      formats on the survival and growth of the litters, suggesting that the housing
      recommendations for breeding female mice as stated in the current Guide for the
      Care and Use of Laboratory Animals should be reconsidered. 

PMID- 25381357
TI  - Role and regulation of CD1d in normal and pathological B cells.
AB  - CD1d is a nonpolymorphic, MHC class I-like molecule that presents phospholipid
      and glycosphingolipid Ags to a subset of CD1d-restricted T cells called invariant
      NKT (iNKT) cells. This CD1d-iNKT cell axis regulates nearly all aspects of both
      the innate and adaptive immune responses. Expression of CD1d on B cells is
      suggestive of the ability of these cells to present Ag to, and form cognate
      interactions with, iNKT cells. In this article, we summarize key evidence
      regarding the role and regulation of CD1d in normal B cells and in humoral
      immunity. We then extend the discussion to B cell disorders, with emphasis on
      autoimmune disease, viral infection, and neoplastic transformation of B lineage
      cells, in which CD1d expression can be altered as a mechanism of immune evasion
      and can have both diagnostic and prognostic importance. Finally, we highlight
      current and future therapeutic strategies that aim to target the CD1d-iNKT cell
      axis in B cells. 

PMID- 25381363
TI  - Publication trends in model organism research.
AB  - In 1990, the National Institutes of Health (NIH) gave some organisms special
      status as designated model organisms. This article documents publication trends
      for these NIH-designated model organisms over the past 40 years. We find that
      being designated a model organism by the NIH does not guarantee an increasing
      publication trend. An analysis of model and nonmodel organisms included in
      GENETICS since 1960 does reveal a sharp decline in the number of publications
      using nonmodel organisms yet no decline in the overall species diversity. We
      suggest that organisms with successful publication records tend to share critical
      characteristics, such as being well developed as standardized, experimental
      systems and being used by well-organized communities with good networks of
      exchange and methods of communication. 

PMID- 25381358
TI  - Development and survival of Th17 cells within the intestines: the influence of
      microbiome- and diet-derived signals.
AB  - Th17 cells have emerged as important mediators of host defense and homeostasis at
      barrier sites, particularly the intestines, where the greatest number and
      diversity of the microbiota reside. A critical balance exists between protection
      of the host from its own microbiota and pathogens and the development of immune
      mediated disease. Breaches of local innate immune defenses provide critical
      stimuli for the induction of Th17 cell development, and additional cues within
      these tissues promote Th17 cell survival and/or plasticity. Normally, this
      results in eradication of the microbial threat and restitution of homeostasis.
      When dysregulated, however, Th17 cells can cause a range of immune-mediated
      diseases, whether directed against Ags derived from the microbiota, such as in
      inflammatory bowel disease, or against self-Ags in a range of autoimmune
      diseases. This review highlights recent discoveries that provide new insights
      into ways in which environmental signals impact Th17 cell development and
      function in the intestines. 

PMID- 25381367
TI  - Gene expression and cytokine profile correlate with mycobacterial growth in a
      human BCG challenge model.
AB  - BACKGROUND: Bacillus Calmette-Guerin (BCG) vaccine is the most widely
      administered vaccine in the world, yet its mechanism of action remains unclear.
      We hypothesize that certain immune pathways are associated with reduced
      mycobacterial growth following BCG challenge in human volunteers. METHODS: We
      used samples from a mycobacterial challenge in which previously BCG-vaccinated or
      BCG-naive adults in the United Kingdom were challenged intradermally with a
      standard dose of BCG. Any remaining BCG was quantified in a skin biopsy specimen
      obtained 2 weeks after challenge and used as a measure of BCG growth and
      functional antimycobacterial immunity. We measured the immune response over the 2
      week challenge, using DNA microarrays and flow cytometry, and correlated this
      with mycobacterial growth. RESULTS: The magnitude of the immune response to BCG
      is greater in previously vaccinated volunteers, and this correlates with reduced
      mycobacterial growth but increased scarring at the vaccination site. In
      particular, the interferon gamma and interleukin 17 pathways are strongly induced
      in previously vaccinated volunteers and correlate with reduced mycobacterial
      growth in this population. CONCLUSION: This study identifies pathways associated
      with control of mycobacterial growth in vivo in human volunteers and supports the
      use of BCG challenge as a tool for evaluating vaccine efficacy and identifying
      mechanisms of antimycobacterial immunity.

PMID- 25381368
TI  - Reply to Manfredi.

PMID- 25381369
TI  - Positive results of immunoglobulin G cytomegalovirus serologic testing and risk
      of severe non-AIDS-related complications in HIV-infected patients.

PMID- 25381371
TI  - Mechanisms for modulation of neural plasticity and axon regeneration by
      chondroitin sulphate.
AB  - Chondroitin sulphate proteoglycans (CSPGs), consisting of core proteins linked to
      one or more chondroitin sulphate (CS) chains, are major extracellular matrix
      (ECM) components of the central nervous system (CNS). Multi-functionality of
      CSPGs can be explained by the diversity in structure of CS chains that undergo
      dynamic changes during development and under pathological conditions. CSPGs,
      together with other ECM components, form mesh-like structures called perineuronal
      nets around a subset of neurons. Enzymatic digestion or genetic manipulation of
      CSPGs reactivates neural plasticity in the adult brain and improves regeneration
      of damaged axons after CNS injury. Recent studies have shown that CSPGs not only
      act as non-specific physical barriers that prevent rearrangement of synaptic
      connections but also regulate neural plasticity through specific interaction of
      CS chains with its binding partners in a manner that depends on the structure of
      the CS chain. 

PMID- 25381370
TI  - Genome-level determination of Plasmodium falciparum blood-stage targets of
      malarial clinical immunity in the Peruvian Amazon.
AB  - BACKGROUND: Persons with blood-stage Plasmodium falciparum parasitemia in the
      absence of symptoms are considered to be clinically immune. We hypothesized that
      asymptomatic subjects with P. falciparum parasitemia would differentially
      recognize a subset of P. falciparum proteins on a genomic scale. METHODS AND
      FINDINGS: Compared with symptomatic subjects, sera from clinically immune,
      asymptomatically infected individuals differentially recognized 51 P. falciparum
      proteins, including the established vaccine candidate PfMSP1. Novel, hitherto
      unstudied hypothetical proteins and other proteins not previously recognized as
      potential vaccine candidates were also differentially recognized. Genes encoding
      the proteins differentially recognized by the Peruvian clinically immune
      individuals exhibited a significant enrichment of nonsynonymous nucleotide
      variation, an observation consistent with these genes undergoing immune
      selection. CONCLUSIONS: A limited set of P. falciparum protein antigens was
      associated with the development of naturally acquired clinical immunity in the
      low-transmission setting of the Peruvian Amazon. These results imply that, even
      in a low-transmission setting, an asexual blood-stage vaccine designed to reduce
      clinical malaria symptoms will likely need to contain large numbers of often
      polymorphic proteins, a finding at odds with many current efforts in the design
      of vaccines against asexual blood-stage P. falciparum.

PMID- 25381372
TI  - Glycobiology of alpha-dystroglycan and muscular dystrophy.
AB  - Most proteins are modified by glycans, which can modulate the biological
      properties and functions of glycoproteins. The major glycans can be classified
      into N-glycans and O-glycans according to their glycan-peptide linkage. This
      review will provide an overview of the O-mannosyl glycans, one subtype of O
      glycans. Originally, O-mannosyl glycan was only known to be present on a limited
      number of glycoproteins, especially alpha-dystroglycan (alpha-DG). However, once
      a clear relationship was established between O-mannosyl glycan and the
      pathological mechanisms of some congenital muscular dystrophies in humans,
      research on the biochemistry and pathology of O-mannosyl glycans has been
      expanding. Because alpha-DG glycosylation is defective in congenital muscular
      dystrophies, which also feature abnormal neuronal migration, these disorders are
      collectively called alpha-dystroglycanopathies. In this article, I will describe
      the structure, biosynthesis and pathology of O-mannosyl glycans. 

PMID- 25381373
TI  - Translational epidemiology: developing and applying theoretical frameworks to
      improve the control of HIV and other sexually transmitted infections.

PMID- 25381374
TI  - Heterogeneity in risk of pelvic inflammatory diseases after chlamydia infection:
      a population-based study in Manitoba, Canada.
AB  - BACKGROUND: The association between chlamydia infection and pelvic inflammatory
      disease (PID) is a key parameter for models evaluating the impact of chlamydia
      control programs. We quantified this association using a retrospective population
      based cohort. METHODS: We used administrative health data sets to construct a
      retrospective population-based cohort of women and girls aged 12-24 years who
      were resident in Manitoba, Canada, between 1992 and 1996. We performed survival
      analysis on a subcohort of individuals who were tested for chlamydia to estimate
      the risk of PID diagnosed in a primary care, outpatient, or inpatient setting
      after >= 1 positive chlamydia test. RESULTS: A total of 73 883 individuals
      contributed 625 621 person years of follow-up. Those with a diagnosis of
      chlamydia had an increased risk of PID over their reproductive lifetime compared
      with those who tested negative (adjusted hazard ratio [AHR], 1.55; 95% confidence
      interval [CI], 1.43-1.70). This risk increased with each subsequent infection:
      the AHR was 1.17 for first reinfection (95% CI, 1.06-1.30) and 1.35 for the
      second (95% CI, 1.04-1.75). The increased risk of PID from reinfection was
      highest in younger individuals (AHR, 4.55 (95% CI, 3.59-5.78) in individuals aged
      12-15 years at the time of their second reinfection, compared with individuals
      older than 30 years). CONCLUSIONS: There is heterogeneity in the risk of PID
      after a chlamydia infection. Describing the progression to PID in mathematical
      models as an average rate may be an oversimplification; more accurate estimates
      of the cost-effectiveness of screening may be obtained by using an individual
      based measure of risk. Health inequalities may be reduced by targeting health
      promotion interventions at sexually active girls younger than 16 years and those
      with a history of chlamydia.

PMID- 25381375
TI  - Circular labor migration and HIV in India: exploring heterogeneity in bridge
      populations connecting areas of high and low HIV infection prevalence.
AB  - BACKGROUND: The emerging human immunodeficiency virus (HIV) epidemics in rural
      areas of India are hypothesized to be linked to circular migrants who are
      introducing HIV from destination areas were the prevalence of HIV infection is
      higher. We explore the heterogeneity in potential roles of circular migrants in
      driving an HIV epidemic in a rural area in north India and examine the
      characteristics of the "sustaining bridge population", which comprises
      individuals at risk of HIV acquisition at destination and of HIV transmission
      into networks at origin capable of sustaining an epidemic. METHODS: Results of a
      behavioral survey of 639 male migrants from Azamgarh district, India, were
      analyzed using chi(2) tests and logistic regression. RESULTS: We estimated the
      size of various subgroups defined by specific sexual behaviors across different
      locations and over time. Only 20% fit our definition of a sustaining bridge
      population, with the majority making no apparent contribution to geographical
      connectedness between high- and low-prevalence areas. However, we found evidence
      of sexual contacts at origin that could potentially sustain an epidemic once HIV
      is introduced. Variables associated with sustaining bridge population membership
      were self-perceived HIV risk, current migrant status, and age. CONCLUSIONS:
      Circular migrants represent a heterogeneous population in terms of their role as
      a bridge group. Self-perception of heightened risk could be exploited in
      designing prevention programs.

PMID- 25381376
TI  - Trends in concurrency, polygyny, and multiple sex partnerships during a decade of
      declining HIV prevalence in eastern Zimbabwe.
AB  - BACKGROUND: Observed declines in the prevalence of human immunodeficiency virus
      (HIV) infection in Zimbabwe have been attributed to population-level reductions
      in sexual partnership numbers. However, it remains unknown whether certain types
      of sex partnerships were more important to this decline. Particular debate
      surrounds the epidemiologic importance of polygyny (the practice of having
      multiple wives). METHODS: We analyze changes in reported multiple partnerships,
      nonmarital concurrency, and polygyny in eastern Zimbabwe during a period of
      declining HIV prevalence, from 1998 to 2011. Trends are reported for adult men
      (age, 17-54 years) and women (age, 15-49 years) from 5 survey rounds of the
      Manicaland HIV/STD Prevention Project, a general-population open cohort study.
      RESULTS: At baseline, 34.2% of men reported multiple partnerships, 11.9% reported
      nonmarital concurrency, and 4.6% reported polygyny. Among women, 4.6% and 1.8%
      reported multiple partnerships and concurrency, respectively. All 3 partnership
      indicators declined by similar relative amounts (around 60%-70%) over the period.
      Polygyny accounted for around 25% of male concurrency. Compared with monogamously
      married men, polygynous men reported higher levels of subsequent
      divorce/separation (adjusted relative risk [RR], 2.92; 95% confidence interval
      [CI], 1.87-4.55) and casual sex partnerships (adjusted RR, 1.63; 95% CI, 1.41
      1.88). CONCLUSIONS: No indicator clearly dominated declines in partnerships.
      Polygyny was surprisingly unstable and, in this population, should not be
      considered a safe form of concurrency.

PMID- 25381377
TI  - The price of sex: condom use and the determinants of the price of sex among
      female sex workers in eastern Zimbabwe.
AB  - BACKGROUND: Higher prices for unprotected sex threaten the high levels of condom
      use that contributed to the decline in Zimbabwe's human immunodeficiency virus
      (HIV) epidemic. To improve understanding of financial pressures competing against
      safer sex, we explore factors associated with the price of commercial sex in
      rural eastern Zimbabwe. METHODS: We collected and analyzed cross-sectional data
      on 311 women, recruited during October-December 2010, who reported that they
      received payment for their most-recent or second-most-recent sex acts in the past
      year. Zero-inflated negative binomial models with robust standard errors
      clustered on female sex worker (FSW) were used to explore social and behavioral
      determinants of price. RESULTS: The median price of sex was $10 (interquartile
      range [IQR], $5-$20) per night and $10 (IQR, $5-$15) per act. Amounts paid in
      cash and commodities did not differ significantly. At the most-recent sex act,
      more-educated FSWs received 30%-74% higher payments. Client requests for condom
      use significantly predicted protected sex (P < .01), but clients paid on average
      42.9% more for unprotected sex. CONCLUSIONS: Within a work environment where
      clients' preferences determine condom use, FSWs effectively use their individual
      capital to negotiate the terms of condom use. Strengthening FSWs' preferences for
      protected sex could help maintain high levels of condom use.

PMID- 25381378
TI  - Risk pathways for gonorrhea acquisition in sex workers: can we distinguish
      confounding from an exposure effect using a priori hypotheses?
AB  - The population distribution of sexually transmitted infections (STIs) varies
      broadly across settings. Although there have been many studies aiming to define
      subgroups at risk of infection that should be a target for prevention
      interventions by identifying risk factors, questions remain about how these risk
      factors interact, how their effects jointly influence the risk of acquisition,
      and their differential importance across populations. Theoretical frameworks
      describing the interrelationships among risk determinants are useful in directing
      both the design and analysis of research studies and interventions. In this
      article, we developed such a framework from a review looking at determinants of
      risk for STI acquisition, using gonorrhea as an index infection. We also propose
      an analysis strategy to interpret the associations found to be significant in
      uniform analyses of observational data. The framework and the hierarchical
      analysis strategy are of particular relevance in the understanding of risk
      formation and might prove useful in identifying determinants that are part of the
      causal pathway and therefore amenable to prevention strategies across
      populations. 

PMID- 25381364
TI  - Mechanisms and regulation of mitotic recombination in Saccharomyces cerevisiae.
AB  - Homology-dependent exchange of genetic information between DNA molecules has a
      profound impact on the maintenance of genome integrity by facilitating error-free
      DNA repair, replication, and chromosome segregation during cell division as well
      as programmed cell developmental events. This chapter will focus on homologous
      mitotic recombination in budding yeast Saccharomyces cerevisiae. However, there
      is an important link between mitotic and meiotic recombination (covered in the
      forthcoming chapter by Hunter et al. 2015) and many of the functions are
      evolutionarily conserved. Here we will discuss several models that have been
      proposed to explain the mechanism of mitotic recombination, the genes and
      proteins involved in various pathways, the genetic and physical assays used to
      discover and study these genes, and the roles of many of these proteins inside
      the cell. 

PMID- 25381380
TI  - How Many HIV infections may be averted by targeting primary infection in men who
      have sex with men? Quantification of changes in transmission-risk behavior, using
      an individual-based model.
AB  - In the United Kingdom, human immunodeficiency virus (HIV) transmission among men
      who have sex with men (MSM) is not under control, despite readily available
      treatment, highlighting the need to design a cost-effective combination
      prevention package. MSM report significantly reduced transmission risk behavior
      following HIV diagnosis. To assess the effectiveness of HIV diagnosis in averting
      transmission during highly infectious primary HIV infection (PHI), we developed a
      stochastic individual-based model to calculate the number of HIV-transmission
      events expected to occur from a cohort of recently infected MSM with and those
      without the behavior changes reported after diagnosis. The model incorporates
      different types of sex acts, incorporates condom use, and distinguishes between
      regular and casual sex partners. The impact on transmission in the 3 months after
      infection depends on PHI duration and testing frequency. If PHI lasts for 3
      months and testing is performed monthly, then behavior changes after diagnosis
      would have reduced estimated transmission events by 49%-52%, from 31-45 to 15-23
      events; a shorter duration of PHI and/or a lower testing frequency reduces the
      number of infections averted. Diagnosing HIV during PHI can markedly reduce
      transmission by changing transmission-risk behavior. Because of the high
      infectivity but short duration of PHI, even short-term behavior change can
      significantly reduce transmission. Our quantification of the number of infections
      averted is an essential component of assessment of the cost-effectiveness of
      strategies to increase detection and diagnoses of PHI. 

PMID- 25381379
TI  - Developing a conceptual framework of seroadaptive behaviors in HIV-diagnosed men
      who have sex with men.
AB  - BACKGROUND: Seroadaptive behaviors are strategies employed by men who have sex
      with men (MSM) to reduce the transmission risk for human immunodeficiency virus
      (HIV). It has been suggested that they contribute to the increasing diagnoses of
      sexually transmitted infections in HIV-diagnosed MSM. To understand the context
      in which the reemerging sexually transmitted infections appear, we developed a
      social epidemiological model incorporating the multiple factors influencing
      seroadaptive behaviors. METHODS: A literature review of seroadaptive behaviors in
      HIV-diagnosed MSM was conducted. The literature was synthesized using a social
      epidemiological perspective. RESULTS: Seroadaptive behaviors are adopted by MSM
      in high-income countries and are a way for HIV-diagnosed men to manage and enjoy
      their sexual lives. Influences are apparent at structural, community,
      interpersonal, and intrapersonal levels. There is little evidence of whether and
      when the behavior forms part of a premeditated strategy; it seems dependent on
      the social context and on time since HIV diagnosis. Social rules of HIV
      disclosure and perception of risk depend on the setting where partners are
      encountered. CONCLUSIONS: Seroadaptive behaviors are strongly context dependent
      and can reduce or increase transmission risk for different infectious diseases.
      Further data collection and mathematical modeling can help us explore the
      specific conditions in more detail.

PMID- 25381381
TI  - Behavioral convergence: implications for mathematical models of sexually
      transmitted infection transmission.
AB  - Recent trends in the behaviors of some groups with high sexual activity and of
      the general population in some countries suggest that sexual behavior profiles of
      high and low sexual activity categories may be converging and may call into
      question the assumptions around sexual mixing that are built into theoretical
      models of sexually transmitted infections (STIs)/human immunodeficiency virus
      (HIV) transmission dynamics. One category of high sexual activity, sex work, has
      been undergoing modification in many societies, becoming more acceptable, more
      dispersed, and larger in volume in some societies and shrinking in others.
      Concurrent with changes in the characteristics of sex work, the accumulating data
      on the sexual behaviors of the general population suggest a shift toward those of
      sex workers, including large numbers of sex partners and short-duration
      partnerships. The closing of the gap between behaviors associated with high and
      low sexual activity may have important implications for theories of sexual
      structure and models of transmission dynamics for STIs, including HIV infection. 

PMID- 25381382
TI  - FOLFOX-containing chemotherapy as a potential cause for pneumothorax.

PMID- 25381383
TI  - A single-center study on predicting outcomes of primary androgen deprivation
      therapy for prostate cancer using the Japan Cancer of the Prostate Risk
      Assessment (J-CAPRA) score.
AB  - OBJECTIVE: Japan Cancer of the Prostate Risk Assessment scores are reportedly
      useful for predicting progression-free survival after primary androgen
      deprivation therapy of prostate cancer patients. This study validated the risk
      assessment at a single institution. METHODS: We studied 255 prostate cancer
      patients given primary androgen deprivation therapy. Progression-free survival,
      cause-specific survival and overall survival were analyzed according to Japan
      Cancer of the Prostate Risk Assessment score-based risk classification. Cases
      with lymph node or distant metastases were subdivided by the risk classification.
      RESULTS: Ages ranged from 50 to 90 years (median: 76.5). Observation periods were
      2-199 (median: 46.5) months. Primary androgen deprivation therapy includes
      combined androgen blockade in 150 cases (58.8%), uncombined luteinizing hormone
      releasing hormone agonist in 97 (38.0%) and uncombined anti-androgenic agent in 8
      (3.2%). Risk classified by Japan Cancer of the Prostate Risk Assessment scores
      was low in 104 cases (40.8%), intermediate in 86 (33.7%) and high in 65 (25.5%).
      The 5-year/10-year progression-free survival rates were 100%/80.8% in the low
      risk, 82.3%/69.5% in the intermediate-risk and 34.7%/16.5% in the high-risk
      group. The 5-year/10-year cause-specific survival rates were 100%/100% in the low
      risk, 90.7%/58.2% in the intermediate-risk and 63%/30.8% in the high-risk group.
      The 5-year/10-year overall survival rates were 87.5%/78.5% in the low-risk,
      76.2%/43.1% in the intermediate-risk and 54.9%/25.4% in the high-risk group. For
      lymph node metastasis, cause-specific survival differed minimally between the
      intermediate- and high-risk groups (P = 0.1118). For distant metastasis, cause
      specific survival differed significantly between the intermediate- and high-risk
      groups (P = 0.0264). CONCLUSIONS: Japan Cancer of the Prostate Risk Assessment
      score-based risk classification is useful for predicting post-primary androgen
      deprivation therapy progression-free survival, cause-specific survival and
      overall survival. Subtyping patients based on Japan Cancer of the Prostate Risk
      Assessment scores is particularly useful for predicting cause-specific survival
      with distant metastasis from prostate cancer.

PMID- 25381384
TI  - Breakthrough pain management using fentanyl buccal tablet (FBT) in combination
      with around-the-clock (ATC) opioids based on the efficacy and safety of FBT, and
      its relationship with ATC opioids: results from an open-label, multi-center study
      in Japanese cancer patients with detailed evaluation.
AB  - OBJECTIVE: Rapid analgesic onset opioids, particularly fentanyl buccal tablet, is
      preferable for managing breakthrough pain. The efficacy and safety of fentanyl
      buccal tablet and its association with around-the-clock opioids needs to be
      explored with an option of dose adjustments, more closely reflecting
      administration in clinical practice. The aim of the study was to assess the
      safety and efficacy of fentanyl buccal tablet in breakthrough pain management in
      combination with around-the-clock opioids with the dose adjustment option, and
      explore the dose adjustment's influence on breakthrough pain management using
      detailed evaluation. METHODS: The 12-week open-label, multi-center study was
      conducted throughout Japan. Cancer patients aged 20 years or older, experiencing
      persistent pain controlled with around-the-clock opioids and breakthrough pain
      with supplemental medications were enrolled. Fentanyl buccal tablet and around
      the-clock opioid doses could be adjusted under protocol-specified conditions.
      Efficacy variables were assessed at each fentanyl buccal tablet administration.
      Safety was assessed mainly by adverse events. RESULTS: All efficacy variables
      showed sustained analgesic effect. Nearly half the patients stayed on the same
      dose; most fentanyl buccal tablet administrations did not require additional
      supplemental medications. Dose increase of fentanyl buccal tablet and around-the
      clock opioids seemed to improve breakthrough pain intensity and frequency,
      respectively. Fentanyl buccal tablet and around-the-clock opioid doses were not
      strongly associated. Treatment-related adverse events were all common with opioid
      treatment and did not increase over time. CONCLUSIONS: Fentanyl buccal tablet can
      stably and safely manage breakthrough pain in cancer patients with independent
      dose adjustment based on detailed evaluation of each patient's condition.
      Breakthrough pain management using fentanyl buccal tablet with around-the-clock
      opioids at optimal doses may be an important factor in palliative care for cancer
      patients with breakthrough pain.

PMID- 25381386
TI  - IL-10 regulates Aicda expression through miR-155.
AB  - Aicda is a critical component of antibody class-switching in B cells. In this
      work, we study the impact of TLR4 activation and IL-10 stimulation on Aicda
      expression in B cells. Through the global analysis of miRNAs in response to TLR4
      activation, in combination with IL-10 stimulation, we identified that IL-10 can
      suppress TLR4-induced miR-155 expression, an effect that resulted in enhanced
      Aicda expression. Furthermore, when preventing miR-155 control of Aicda
      expression, by genetic mutation of its target site in the Aicda mRNA, IL-10 could
      further potentiate Aicda expression. Given that miR-155 expression is lost, and
      expression levels of both Aicda and IL-10 are high in diseases, such as Burkitt's
      lymphoma, our results suggest a stringent and sophisticated control of Aicda by a
      novel IL-10/miR-155 axis, where the imbalance of IL-10 and/or miR-155 may
      contribute to disease pathogenesis. 

PMID- 25381385
TI  - Complement protein C1q bound to apoptotic cells suppresses human macrophage and
      dendritic cell-mediated Th17 and Th1 T cell subset proliferation.
AB  - A complete genetic deficiency of the complement protein C1q results in SLE with
      nearly 100% penetrance in humans, but the molecular mechanisms responsible for
      this association have not yet been fully determined. C1q opsonizes ACs for
      enhanced ingestion by phagocytes, such as Mphi and iDCs, avoiding the
      extracellular release of inflammatory DAMPs upon loss of the membrane integrity
      of the dying cell. We previously showed that human monocyte-derived Mphi and DCs
      ingesting autologous, C1q-bound LALs (C1q-polarized Mphi and C1q-polarized DCs),
      enhance the production of anti-inflammatory cytokines, and reduce proinflammatory
      cytokines relative to Mphi or DC ingesting LAL alone. Here, we show that C1q
      polarized Mphi have elevated PD-L1 and PD-L2 and suppressed surface CD40, and C1q
      polarized DCs have higher surface PD-L2 and less CD86 relative to Mphi or DC
      ingesting LAL alone, respectively. In an MLR, C1q-polarized Mphi reduced
      allogeneic and autologous Th17 and Th1 subset proliferation and demonstrated a
      trend toward increased Treg proliferation relative to Mphi ingesting LAL alone.
      Moreover, relative to DC ingesting AC in the absence of C1q, C1q-polarized DCs
      decreased autologous Th17 and Th1 proliferation. These data demonstrate that a
      functional consequence of C1q-polarized Mphi and DC is the regulation of Teff
      activation, thereby "sculpting" the adaptive immune system to avoid autoimmunity,
      while clearing dying cells. It is noteworthy that these studies identify novel
      target pathways for therapeutic intervention in SLE and other autoimmune
      diseases. 

PMID- 25381387
TI  - Decidual natural killer cell receptor expression is altered in pregnancies with
      impaired vascular remodeling and a higher risk of pre-eclampsia.
AB  - During pregnancy, a specialized type of NK cell accumulates in the lining of the
      uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK
      cells are functionally and phenotypically distinct from PB NK and are implicated
      in regulation of trophoblast transformation of the uterine spiral arteries, which
      if inadequately performed, can result in pregnancy disorders. Here, we have used
      uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure
      of the extent of transformation of the spiral arteries to identify pregnancies
      with a high RI, indicative of impaired spiral artery remodeling. We have used
      flow cytometry to examine dNK cells isolated from these pregnancies compared with
      those from pregnancies with a normal RI. We report a reduction in the proportion
      of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1,
      receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the
      decidua was examined by receptor blocking in trophoblast coculture and altered
      dNK expression of the cytokines CXCL10 and TNF-alpha, which regulate trophoblast
      behavior. These results indicate that dNK cells from high RI pregnancies may
      display altered interactions with trophoblast via decreased expression of HLA
      binding cell-surface receptors, impacting on successful transformation of the
      uterus for pregnancy. 

PMID- 25381388
TI  - The immunophenotype of mast cells and its utility in the diagnostic work-up of
      systemic mastocytosis.
AB  - SM comprises a heterogeneous group of disorders, characterized by an abnormal
      accumulation of clonal MCs in 1 or more tissues, frequently involving the skin
      and BM. Despite the fact that most adult patients (>90%) carry the same genetic
      lesion (D816V KIT mutation), the disease presents with multiple variants with
      very distinct clinical and biologic features, a diverse prognosis, and different
      therapeutic requirements. Recent advances in the standardization of the study of
      BM MC by MFC allowed reproducible identification and characterization of
      normal/reactive MCs and their precursors, as well as the establishment of the
      normal MC maturational profiles. Analysis of large groups of patients versus
      normal/reactive samples has highlighted the existence of aberrant MC phenotypes
      in SM, which are essential for the diagnosis of the disease. In turn, 3 clearly
      distinct and altered maturation-associated immunophenotypic profiles have been
      reported recently in SM, which provide criteria for the distinction between ISM
      patients with MC-restricted and multilineage KIT mutation; thus, immunphenotyping
      also contributes to prognostic stratification of ISM, particularly when analysis
      of the KIT mutation on highly purified BM cells is not routinely available in the
      diagnostic work-up of the disease. 

PMID- 25381389
TI  - Down-regulation of survivin alleviates experimental arthritis.
AB  - Survivin is a proto-oncogene that regulates cell division and apoptosis. It is a
      molecular marker of cancer. Recently, survivin has emerged as a feature of RA,
      associated with severe joint damage and poor treatment response. The present
      study examined if inhibition of survivin affects experimental arthritis, which
      was induced in mBSA-immunized mice by an injection of mBSA in the knee joint or
      developed spontaneously in collagen type II-immunized mice. The inhibition of
      survivin transcription by a lentivirus shRNA construct alleviated joint
      inflammation and reduced bone damage. The inhibition of survivin reduced the
      levels of metalloproteinases, beta-catenin, and vimentin, limiting the invasive
      capacity of synovia, while no inhibition of osteoclastogenesis could be found.
      The inhibition of survivin led to a p53-independent reduction of T cell
      proliferation and favored the transcription and activity of Blimp-1, which
      limited IL-2 production and facilitated formation of regulatory Foxp3(+)CD4(+)
      and effector CD8(+) T cells. The study shows that the inhibition of survivin is
      sufficient to reduce joint inflammation and bone damage in preclinical models of
      arthritis. Antiarthritic effects of survivin inhibition are related to p53
      independent control of lymphocyte proliferation. 

PMID- 25381391
TI  - RE: Effects of Helicobacter pylori treatment on gastric cancer incidence and
      mortality in subgroups. Response.

PMID- 25381390
TI  - Hypochlorous acid via peroxynitrite activates protein kinase Ctheta and insulin
      resistance in adipocytes.
AB  - We recently reported that genetic deletion of myeloperoxidase (MPO) alleviates
      obesity-related insulin resistance in mice in vivo. How MPO impairs insulin
      sensitivity in adipocytes is poorly characterized. As hypochlorous acid (HOCl) is
      a principal oxidant product generated by MPO, we evaluated the effects of HOCl on
      insulin signaling in adipocytes differentiated from 3T3-L1 cells. Exposure of 3T3
      L1 adipocytes to exogenous HOCl (200 MUmol/l) attenuated insulin-stimulated 2
      deoxyglucose uptake, GLUT4 translocation, and insulin signals, including tyrosine
      phosphorylation of insulin receptor substrate 1 (IRS1) and phosphorylation of
      Akt. Furthermore, treatment with HOCl induced phosphorylation of IRS1 at serine
      307, inhibitor kappaB kinase (IKK), c-Jun NH2-terminal kinase (JNK), and
      phosphorylation of PKCtheta (PKCtheta). In addition, genetic and pharmacological
      inhibition of IKK and JNK abolished serine phosphorylation of IRS1 and impairment
      of insulin signaling by HOCl. Furthermore, knockdown of PKCtheta using siRNA
      transfection suppressed phosphorylation of IKK and JNK and consequently
      attenuated the HOCl-impaired insulin signaling pathway. Moreover, activation of
      PKCtheta by peroxynitrite was accompanied by increased phosphorylation of IKK,
      JNK, and IRS1-serine 307. In contrast, ONOO(-) inhibitors abolished HOCl-induced
      phosphorylation of PKCtheta, IKK, JNK, and IRS1-serine 307, as well as insulin
      resistance. Finally, high-fat diet (HFD)-induced insulin resistance was
      associated with enhanced phosphorylation of PKCtheta, IKK, JNK, and IRS1 at
      serine 307 in white adipose tissues from WT mice, all of which were not found in
      Mpo knockout mice fed HFDs. We conclude that HOCl impairs insulin signaling
      pathway by increasing ONOO(-) mediated phosphorylation of PKCtheta, resulting in
      phosphorylation of IKK/JNK and consequent serine phosphorylation of IRS1 in
      adipocytes. 

PMID- 25381392
TI  - RE: Effects of helicobacter pylori treatment on gastric cancer incidence and
      mortality in subgroups.

PMID- 25381394
TI  - DPYD variants to predict 5-FU toxicity: the ultimate proof.

PMID- 25381393
TI  - DPYD variants as predictors of 5-fluorouracil toxicity in adjuvant colon cancer
      treatment (NCCTG N0147).
AB  - BACKGROUND: Previous studies have suggested the potential importance of three
      DPYD variants (DPYD*2A, D949V, and I560S) with increased 5-FU toxicity. Their
      individual associations, however, in 5-FU-based combination therapies, remain
      controversial and require further systematic study in a large patient population
      receiving comparable treatment regimens with uniform clinical data. METHODS: We
      genotyped 2886 stage III colon cancer patients treated adjuvantly in a randomized
      phase III trial with FOLFOX or FOLFIRI, alone or combined with cetuximab, and
      tested the individual associations between functionally deleterious DPYD variants
      and toxicity. Logistic regressions were used to assess univariate and
      multivariable associations. All statistical tests were two-sided. RESULTS: In
      2594 patients with complete adverse event (AE) data, the incidence of grade 3 or
      greater 5FU-AEs in DPYD*2A, I560S, and D949V carriers were 22/25 (88.0%), 2/4
      (50.0%), and 22/27 (81.5%), respectively. Statistically significant associations
      were identified between grade 3 or greater 5FU-AEs and both DPYD*2A (odds ratio
      [OR] = 15.21, 95% confidence interval [CI] = 4.54 to 50.96, P < .001) and D949V
      (OR = 9.10, 95% CI = 3.43 to 24.10, P < .001) variants. Statistical significance
      remained after adjusting for multiple variables. The DPYD*2A variant
      statistically significantly associated with the specific AEs nausea/vomiting (P =
      .007) and neutropenia (P < .001), whereas D949V statistically significantly
      associated with dehydration (P = .02), diarrhea (P = .003), leukopenia (P =
      .002), neutropenia (P < .001), and thrombocytopenia (P < .001). Although two
      patients with I560S had grade>=3 5FU-AEs; a statistically significant association
      could not be demonstrated because of its low frequency (P = .48). CONCLUSION: In
      the largest study to date, statistically significant associations were found
      between DPYD variants (DPYD*2A and D949V) and increased incidence of grade 3 or
      greater 5FU-AEs in patients treated with adjuvant 5-FU-based combination
      chemotherapy.

PMID- 25381396
TI  - Endpoints for the evaluation of breast cancer treatments.

PMID- 25381395
TI  - Maastricht Delphi consensus on event definitions for classification of recurrence
      in breast cancer research.
AB  - BACKGROUND: In breast cancer studies, many different endpoints are used.
      Definitions are often not provided or vary between studies. For instance, "local
      recurrence" may include different components in similar studies. This limits
      transparency and comparability of results. This project aimed to reach consensus
      on the definitions of local event, second primary breast cancer, regional and
      distant event for breast cancer studies. METHODS: The RAND-UCLA Appropriateness
      method (modified Delphi method) was used. A Consensus Group of international
      breast cancer experts was formed, including representatives of all involved
      clinical disciplines. Consensus was reached in two rounds of online
      questionnaires and one meeting. RESULTS: Twenty-four international breast cancer
      experts participated. Consensus was reached on 134 items in four categories.
      Local event is defined as any epithelial breast cancer or ductal carcinoma in
      situ (DCIS) in the ipsilateral breast, or skin and subcutaneous tissue on the
      ipsilateral thoracic wall. Second primary breast cancer is defined as epithelial
      breast cancer in the contralateral breast. Regional events are breast cancer in
      ipsilateral lymph nodes. A distant event is breast cancer in any other location.
      Therefore, this includes metastasis in contralateral lymph nodes and breast
      cancer involving the sternal bone. If feasible, tissue sampling of a first,
      solitary, lesion suspected for metastasis is highly recommended. CONCLUSION: This
      project resulted in consensus-based event definitions for classification of
      recurrence in breast cancer research. Future breast cancer research projects
      should adopt these definitions to increase transparency. This should facilitate
      comparison of results and conducting reviews as well as meta-analysis.

PMID- 25381397
TI  - Re: Time to smoke first morning cigarette (TTFC) and lung cancer in a case
      control study.

PMID- 25381398
TI  - Response.

PMID- 25381399
TI  - The journey continues.

PMID- 25381400
TI  - Advances in pain management: game changers in knee arthroplasty.
AB  - Over the past 30 years there have been many improvements in implant fixation,
      correction of deformity, improved polyethylene wear, and survival after knee
      replacement. The work over the last decade has focused on less invasive surgical
      techniques, multimodal pain management protocols, more rapid functional recovery
      and reduced length of stay, aiming to minimise the side effects of treatment
      while maintaining function and implant durability. When combined and standardised
      these pre-, intra- and post-operative factors have now facilitated outpatient
      knee replacement procedures for unicompartmental replacement, patella femoral
      arthroplasty and total knee replacement (TKR). We have found liposomal
      bupivacaine, with potential for longer therapeutic action, to be a helpful
      adjunct and describe our current pain management program. The next step in our
      multimodal program is to improve the duration of patient satisfaction and reduce
      cost and length of stay after TKR.

PMID- 25381401
TI  - Cartilage restoration of the hip using fresh osteochondral allograft: resurfacing
      the potholes.
AB  - Cartilage defects of the hip cause significant pain and may lead to arthritic
      changes that necessitate hip replacement. We propose the use of fresh
      osteochondral allografts as an option for the treatment of such defects in young
      patients. Here we present the results of fresh osteochondral allografts for
      cartilage defects in 17 patients in a prospective study. The underlying diagnoses
      for the cartilage defects were osteochondritis dissecans in eight and avascular
      necrosis in six. Two had Legg-Calve-Perthes and one a femoral head fracture. Pre
      operatively, an MRI was used to determine the size of the cartilage defect and
      the femoral head diameter. All patients underwent surgical hip dislocation with a
      trochanteric slide osteotomy for placement of the allograft. The mean age at
      surgery was 25.9 years (17 to 44) and mean follow-up was 41.6 months (3 to 74).
      The mean Harris hip score was significantly better after surgery (p<0.01) and 13
      patients had fair to good outcomes. One patient required a repeat allograft, one
      patient underwent hip replacement and two patients are awaiting hip replacement.
      Fresh osteochondral allograft is a reasonable treatment option for hip cartilage
      defects in young patients.

PMID- 25381402
TI  - Metal-on-metal hip surface replacement: the routine use is not justified.
AB  - Metal-on-metal resurfacing of the hip (MoMHR) has enjoyed a resurgence in the
      last decade, but is now again in question as a routine option for osteoarthritis
      of the hip. Proponents of hip resurfacing suggest that its survival is superior
      to that of conventional hip replacement (THR), and that hip resurfacing is less
      invasive, is easier to revise than THR, and provides superior functional
      outcomes. Our argument serves to illustrate that none of these proposed
      advantages have been realised and new and unanticipated serious complications,
      such as pseudotumors, have been associated with the procedure. As such, we feel
      that the routine use of MoMHR is not justified.

PMID- 25381403
TI  - Large diameter femoral heads: is bigger always better?
AB  - Dislocation remains among the most common complications of, and reasons for,
      revision of both primary and revision total hip replacements (THR). Hence, there
      is great interest in maximising stability to prevent this complication. Head size
      has been recognised to have a strong influence on the risk of dislocation post
      operatively. As femoral head size increases, stability is augmented, secondary to
      an increase in impingement-free range of movement. Larger head sizes also greatly
      increase the 'jump distance' required for the head to dislocate in an
      appropriately positioned cup. Level-one studies support the use of larger
      diameter heads as they decrease the risk of dislocation following primary and
      revision THR. Highly cross-linked polyethylene has allowed us to increase femoral
      head size, without a marked increase in wear. However, the thin polyethylene
      liners necessary to accommodate larger heads may increase the risk of liner
      fracture and larger heads have also been implicated in causing soft-tissue
      impingement resulting in groin pain. Larger diameter heads also impart larger
      forces on the femoral trunnion, which may contribute to corrosion, metal release,
      and adverse local tissue reactions. Alternative large bearings including large
      ceramic heads and dual mobility bearings may mitigate some of these risks, and
      several of these devices have been used with clinical success.

PMID- 25381404
TI  - The neuromuscularly challenged patient: total hip replacement is now an option.
AB  - Degenerative problems of the hip in patients with childhood and adult onset
      neuromuscular disorders can be challenging to treat. Many orthopaedic surgeons
      are reluctant to recommend total hip replacement (THR) for patients with
      underlying neuromuscular disorders due to the perceived increased risks of
      dislocation, implant loosening, and lack of information about the functional
      outcomes and potential benefits of these procedures in these patients. Modular
      femoral components and alternative bearings which facilitate the use of large
      femoral heads, constrained acetabular components and perhaps more importantly, a
      better understanding about the complications and outcomes of THR in the patient
      with neuromuscular disorders, make this option viable. This paper will review the
      current literature and our experience with THR in the more frequently encountered
      neuromuscular disorders.

PMID- 25381405
TI  - A mini-anterior approach to the hip for total joint replacement: optimising
      results: improving hip joint replacement outcomes.
AB  - Direct anterior approaches to the hip have gained popularity as a minimally
      invasive method when performing primary total hip replacement (THR). A
      retrospective review of a single institution joint registry was performed in
      order to compare patient outcomes after THR using the Anterior Supine
      Intermuscular (ASI) approach versus a more conventional direct lateral approach.
      An electronic database identified 1511 patients treated with 1690 primary THRs
      between January 2006 and December 2010. Our results represent a summary of
      findings from our previously published work. We found that patients that
      underwent an ASI approach had faster functional recovery and higher Harris hip
      scores in the early post-operative period when compared with patients who had a
      direct lateral approach The overall complication rate in our ASI group was
      relatively low (1.7%) compared with other series using the same approach. The
      most frequent complication was early periprosthetic femoral fractures (0.9%). The
      dislocation rate in our series was 0.4% and the prosthetic joint infection rate
      was 0.1%. We suggest that the ASI approach is acceptable and safe when performing
      THR and encourages early functional recovery of our patients.

PMID- 25381406
TI  - Acetabular distraction: an alternative for severe acetabular bone loss and
      chronic pelvic discontinuity.
AB  - Acetabular bone loss is a challenging problem facing the revision total hip
      replacement surgeon. Reconstruction of the acetabulum depends on the presence of
      anterosuperior and posteroinferior pelvic column support for component fixation
      and stability. The Paprosky classification is most commonly used when determining
      the location and degree of acetabular bone loss. Augments serve the function of
      either providing primary construct stability or supplementary fixation. When a
      pelvic discontinuity is encountered we advocate the use of an acetabular
      distraction technique with a jumbo cup and modular porous metal acetabular
      augments for the treatment of severe acetabular bone loss and associated chronic
      pelvic discontinuity.

PMID- 25381407
TI  - Femoral neck fractures: a changing paradigm.
AB  - Surgical interventions consisting of internal fixation (IF) or total hip
      replacement (THR) are required to restore patient mobility after hip fractures.
      Conventionally, this decision was based solely upon the degree of fracture
      displacement. However, in the last ten years, there has been a move to
      incorporate patient characteristics into the decision making process. Research
      demonstrating that joint replacement renders superior functional results when
      compared with IF, in the treatment of displaced femoral neck fractures, has
      swayed the pendulum in favour of THR. However, a high risk of dislocation has
      always been the concern. Fortunately, there are newer technologies and
      alternative surgical approaches that can help reduce the risk of dislocation. The
      authors propose an algorithm for the treatment of femoral neck fractures: if
      minimally displaced, in the absence of hip joint arthritis, IF should be
      performed; if arthritis is present, or the fracture is displaced, then THR is
      preferred.

PMID- 25381408
TI  - Periprosthetic fractures: bespoke solutions.
AB  - We are currently facing an epidemic of periprosthetic fractures around the hip.
      They may occur either during surgery or post-operatively. Although the acetabulum
      may be involved, the femur is most commonly affected. We are being presented with
      new, difficult fracture patterns around cemented and cementless implants, and we
      face the challenge of an elderly population who may have grossly deficient bone
      and may struggle to rehabilitate after such injuries. The correct surgical
      management of these fractures is challenging. This article will review the
      current choices of implants and techniques available to deal with periprosthetic
      fractures of the femur.

PMID- 25381409
TI  - Non-modular tapered fluted titanium stems in hip revision surgery: gaining
      attention.
AB  - Non-modular tapered fluted, titanium stems are available for use in femoral
      revision. The combination of taper and flutes on the stem provides axial and
      rotational stability, respectively. The material and surface properties of the
      stem promotes bone on-growth. If the surgeon is confident and reasonably
      experienced in the surgical use of this sort of design and the case is relatively
      straightforward, a non-modular design is effective. It also potentially reduces
      implant inventory, and circumvents the potential problems of taper junction
      corrosion and fatigue fracture. There are reports of excellent survival, good
      clinical and functional results and evidence of subsequent increase in proximal
      bone stock.

PMID- 25381411
TI  - Partial two-stage exchange of the infected total hip replacement using disposable
      spacer moulds.
AB  - The common recommended treatment for infected total hip replacement is two-staged
      exchange including removal of all components. However, removal of well-fixed
      femoral stems can result in structural bone damage. We recently reported on an
      alternative treatment of partial two-stage exchange used in selected cases, in
      which a well-fixed femoral stem was left and only the acetabular component
      removed, the joint space was debrided thoroughly, an antibiotic-laden
      polymethylmethacrylate spacer was moulded using a bulb-type syringe and placed in
      the acetabulum, intravenous antibiotics were administered during the interval,
      and delayed re-implantation was performed. In 19 patients treated with this
      technique from January 2000 to January 2011, 89% were free of infection at a mean
      follow-up of four years (2 to 11). Since then, disposable silicone moulds have
      become available to fabricate spacers in separate femoral and head units. The
      head spacer mould, which incorporates various neck taper adapter options, greatly
      facilitates the technique of partial two-stage exchange. We report our early
      experience using disposable silicone head spacer moulds for partial two-stage
      exchange in seven patients with infected primary hip replacements.

PMID- 25381410
TI  - The challenge of methicillin resistant staphylococcal infection after total hip
      replacement: overlooked or overstated?
AB  - Advances in the treatment of periprosthetic joint infections of the hip have once
      more pushed prosthesis preserving techniques into the limelight. At the same
      time, the common infecting organisms are evolving to become more resistant to
      conventional antimicrobial agents. Whilst the epidemiology of resistant
      staphylococci is changing, a number of recent reports have advocated the use of
      irrigation and debridement and one-stage revision for the treatment of
      periprosthetic joint infections due to resistant organisms. This review presents
      the available evidence for the treatment of periprosthetic joint infections of
      the hip, concentrating in particular on methicillin resistant staphylococci.

PMID- 25381412
TI  - The revision acetabulum--allograft and bone substitutes: vestigial organs for
      bone deficiency.
AB  - A common situation presenting to the orthopaedic surgeon today is a worn
      acetabular liner with substantial acetabular and pelvic osteolysis. The surgeon
      has many options for dealing with osteolytic defects. These include allograft,
      calcium based substitutes, demineralised bone matrix, or combinations of these
      options with or without addition of platelet rich plasma. To date there are no
      clinical studies to determine the efficacy of using bone-stimulating materials in
      osteolytic defects at the time of revision surgery and there are surprisingly few
      studies demonstrating the clinical efficacy of these treatment options. Even when
      radiographs appear to demonstrate incorporation of graft material CT studies have
      shown that incorporation is incomplete. The surgeon, in choosing a graft material
      for a surgical procedure must take into account the efficacy, safety, cost and
      convenience of that material.

PMID- 25381413
TI  - Acetabular distraction: an alternative approach to pelvic discontinuity in failed
      total hip replacement.
AB  - A pelvic discontinuity occurs when the superior and inferior parts of the hemi
      pelvis are no longer connected, which is difficult to manage when associated with
      a failed total hip replacement. Chronic pelvic discontinuity is found in 0.9% to
      2.1% of hip revision cases with risk factors including severe pelvic bone loss,
      female gender, prior pelvic radiation and rheumatoid arthritis. Common treatment
      options include: pelvic plating with allograft, cage reconstruction, custom
      triflange implants, and porous tantalum implants with modular augments. The
      optimal technique is dependent upon the degree of the discontinuity, the amount
      of available bone stock and the likelihood of achieving stable healing between
      the two segments. A method of treating pelvic discontinuity using porous tantalum
      components with a distraction technique that achieves both initial stability and
      subsequent long-term biological fixation is described.

PMID- 25381414
TI  - Soft-tissue and alignment correction: the use of smart trials in total knee
      replacement.
AB  - Total knee replacement (TKR) smart tibial trials have load-bearing sensors which
      will show quantitative compartment pressure values and femoral-tibial tracking
      patterns. Without smart trials, surgeons rely on feel and visual estimation of
      imbalance to determine if the knee is optimally balanced. Corrective soft-tissue
      releases are performed with minimal feedback as to what and how much should be
      released. The smart tibial trials demonstrate graphically where and how much
      imbalance is present, so that incremental releases can be performed. The smart
      tibial trials now also incorporate accelerometers which demonstrate the axial
      alignment. This now allows the surgeon the option to perform a slight recut of
      the tibia or femur to provide soft-tissue balance without performing soft-tissue
      releases. Using a smart tibial trial to assist with soft-tissue releases or bone
      re-cuts, improved patient outcomes have been demonstrated at one year in a
      multicentre study of 135 patients (135 knees).

PMID- 25381415
TI  - Avoiding patellar complications in total knee replacement.
AB  - Patellofemoral complications are common after total knee replacement (TKR).
      Leaving the patellar unsurfaced after TKR may lead to complications such as
      anterior knee pain, and re-operation to surface it. Complications after patellar
      resurfacing include patellar fracture, aseptic loosening, patellar instability,
      polyethylene wear, patellar clunk and osteonecrosis. Historically, patellar
      complications account for one of the larger proportions of causes of failure in
      TKR, however, with contemporary implant designs, complication rates have
      decreased. Most remaining failures relate to patellofemoral tracking.
      Understanding the causes of patellofemoral maltracking is essential to prevent
      these complications as well as manage them when they occur.

PMID- 25381416
TI  - Cementless total knee replacement fixation: a contemporary durable solution-
      affirms.
AB  - A retrospective review was performed of patients undergoing primary cementless
      total knee replacement (TKR) using porous tantalum performed by a group of
      surgical trainees. Clinical and radiological follow-up involved 79 females and 26
      males encompassing 115 knees. The mean age was 66.9 years (36 to 85). Mean follow
      up was 7 years (2 to 11). Tibial and patellar components were porous tantalum
      monoblock implants, and femoral components were posterior stabilised (PS) in
      design with cobalt-chromium fibre mesh. Radiological assessments were made for
      implant positioning, alignment, radiolucencies, lysis, and loosening. There was
      95.7% survival of implants. There was no radiological evidence of loosening and
      no osteolysis found. No revisions were performed for aseptic loosening. Average
      tibial component alignment was 1.4 degrees  of varus (4 degrees of valgus to 9
      degrees  varus), and 6.2 degrees  (3 degrees  anterior to 15 degrees  posterior)
      of posterior slope. Mean femoral component alignment was 6.6 degrees  (1 degrees 
      to 11 degrees ) of valgus. Mean tibiofemoral alignment was 5.6 degrees  of valgus
      (7 degrees  varus to 16 degrees  valgus). Patellar tilt was a mean of 2.4 degrees
      lateral (5 degrees  medial to 28 degrees  lateral). Patient satisfaction with
      improvement in pain was 91%. Cementless TKR incorporating porous tantalum yielded
      good clinical and radiological outcomes at a mean of follow-up of seven-years.

PMID- 25381417
TI  - The role of hinges in primary total knee replacement.
AB  - The use of hinged implants in primary total knee replacement (TKR) should be
      restricted to selected indications and mainly for elderly patients. Potential
      indications for a rotating hinge or pure hinge implant in primary TKR include:
      collateral ligament insufficiency, severe varus or valgus deformity (>20 degrees
      ) with necessary relevant soft-tissue release, relevant bone loss including
      insertions of collateral ligaments, gross flexion-extension gap imbalance,
      ankylosis, or hyperlaxity. Although data reported in the literature are
      inconsistent, clinical results depend on implant design, proper technical use,
      and adequate indications. We present our experience with a specific implant type
      that we have used for over 30 years and which has given our elderly patients good
      mid-term results. Because revision of implants with long cemented stems can be
      very challenging, an effort should be made in the future to use shorter stems in
      modular versions of hinged implants.

PMID- 25381418
TI  - Patient dissatisfaction following total knee replacement: a growing concern?
AB  - A national, multi-centre study was designed in which a questionnaire quantifying
      the degree of patient satisfaction and residual symptoms in patients following
      total knee replacement (TKR) was administered by an independent, blinded third
      party survey centre. A total of 90% of patients reported satisfaction with the
      overall functioning of their knee, but 66% felt their knee to be 'normal', with
      the reported incidence of residual symptoms and functional problems ranging from
      33% to 54%. Female patients and patients from low-income households had increased
      odds of reporting dissatisfaction. Neither the use of contemporary implant
      designs (gender-specific, high-flex, rotating platform) or custom cutting guides
      (CCG) with a neutral mechanical axis target improved patient-perceived outcomes.
      However, use of a CCG to perform a so-called kinematically aligned TKR showed a
      trend towards more patients reporting their knee to feel 'normal' when compared
      with a so called mechanically aligned TKR This data shows a degree of
      dissatisfaction and residual symptoms following TKR, and that several recent
      modifications in implant design and surgical technique have not improved the
      current situation.

PMID- 25381419
TI  - Why knee replacements fail in 2013: patient, surgeon, or implant?
AB  - Previous studies of failure mechanisms leading to revision total knee replacement
      (TKR) performed between 1986 and 2000 determined that many failed early, with a
      disproportionate amount accounted for by infection and implant-associated factors
      including wear, loosening and instability. Since then, efforts have been made to
      improve implant performance and instruct surgeons in best practice. Recently our
      centre participated in a multi-centre evaluation of 844 revision TKRs from 2010
      to 2011. The purpose was to report a detailed analysis of failure mechanisms over
      time and to see if failure modes have changed over the past 10 to 15 years.
      Aseptic loosening was the predominant mechanism of failure (31.2%), followed by
      instability (18.7%), infection (16.2%), polyethylene wear (10.0%), arthrofibrosis
      (6.9%) and malalignment (6.6%). The mean time to failure was 5.9 years (ten days
      to 31 years), 35.3% of all revisions occurred at less than two years, and 60.2%
      in the first five years. With improvements in implant and polyethylene
      manufacture, polyethylene wear is no longer a leading cause of failure. Early
      mechanisms of failure are primarily technical errors. In addition to improving
      implant longevity, industry and surgeons must work together to decrease these
      technical errors. All reports on failure of TKR contain patients with unexplained
      pain who not infrequently have unmet expectations. Surgeons must work to achieve
      realistic patient expectations pre-operatively, and therefore, improve patient
      satisfaction post-operatively.

PMID- 25381420
TI  - The problem total knee replacement: systematic, comprehensive and efficient
      evaluation.
AB  - There are many reasons why a total knee replacement (TKR) may fail and qualify
      for revision. Successful revision surgery depends as much on accurate assessment
      of the problem TKR as it does on revision implant design and surgical technique.
      Specific modes of failure require specific surgical solutions. Causes of failure
      are often presented as a list or catalogue, without a system or process for
      making a decision. In addition, strict definitions and consensus on modes of
      failure are lacking in published series and registry data. How we approach the
      problem TKR is an essential but neglected aspect of understanding knee
      replacement surgery. It must be carried out systematically, comprehensively and
      efficiently. Eight modes of failure are described: 1) sepsis; 2) extensor
      discontinuity; 3) stiffness; 4) tibial- femoral instability; 5) patellar
      tracking; 6) aseptic loosening and osteolysis; 7) periprosthetic fracture and 8)
      component breakage. A ninth 'category', unexplained pain is an indication for
      further investigation but not surgery.

PMID- 25381421
TI  - The unstable knee: wobble and buckle.
AB  - Instability after total knee replacement (TKR) accounts for 10% to 22% of
      revision procedures. All patients who present for evaluation of instability
      require a thorough history to be taken and physical examination, as well as
      appropriate imaging. Deep periprosthetic infection must be ruled out by
      laboratory testing and an aspiration of the knee must be carried out. The three
      main categories of instability include flexion instability, extension instability
      (symmetric and asymmetric), and genu recurvatum. Most recently, the aetiologies
      contributing to, and surgical manoeuvres required to correct, flexion instability
      have been elucidated. While implant design and patient-related factors may
      certainly contribute to the aetiology, surgical technique is also a significant
      factor in all forms of post-operative instability.

PMID- 25381422
TI  - Cemented stems: a requisite in revision total knee replacement.
AB  - Stems may improve fixation and stability of components during revision total knee
      replacement. However, the choice between cemented and cementless stems is not a
      clear one. Cemented stems offer several advantages in terms of versatility,
      mechanical stability, surgical technique and clinical outcome over their
      cementless counterpart.

PMID- 25381423
TI  - Porous metal metaphyseal cones for severe bone loss: when only metal will do.
AB  - Metaphyseal bone loss is common with revision total knee replacement (RTKR).
      Using the Anderson Orthopaedic Research Institute (AORI) classification, type 2-B
      and type 3 defects usually require large metal blocks, bulk structural allograft
      or highly porous metal cones. Tibial and femoral trabecular metal metaphyseal
      cones are a unique solution for large bone defects. These cones substitute for
      bone loss, improve metaphyseal fixation, help correct malalignment, restore the
      joint line and may permit use of a shorter stem. The technique for insertion
      involves sculpturing of the remaining bone with a high speed burr and rasp,
      followed by press-fit of the cone into the metaphysis. The fixation and
      osteoconductive properties of the porous cone outer surface allow ingrowth and
      encourage long-term biological fixation. The revision knee component is then
      cemented into the porous cone inner surface, which provides superior fixation
      compared with cementing into native but deficient metaphyseal bone. The
      advantages of the cone compared with allograft include: technical ease,
      biological fixation, no resorption, and possibly a lower risk of infection. The
      disadvantages include: difficult extraction and relatively short-term follow-up.
      Several studies using cones report promising short-term results for the
      reconstruction of large bone defects in RTKR.

PMID- 25381424
TI  - The multiply-operated total knee replacement patient: salvage options.
AB  - Although the vast majority of patients that undergo total knee replacement have
      satisfactory outcomes with a generally low complication rate, occasionally a
      patient will be encountered that has had multiple failed surgeries, and now
      reaches a crossroad as to whether limb salvage will be acceptable or not.

PMID- 25381425
TI  - Understanding the role of rituximab in ANCA GN: regressing toward the mean.

PMID- 25381426
TI  - Endothelial cell antibodies associated with novel targets and increased
      rejection.
AB  - The initial contact point between a recipient's immune system and a transplanted
      graft is the vascular endothelium. Clinical studies suggest a pathogenic role for
      non-HLA antiendothelial cell antibodies (AECAs) in allograft rejection; however,
      evidence linking AECAs of known specificity to in vivo vascular injury is
      lacking. Here, we used high-density protein arrays to identify target antigens
      for AECAs isolated from the sera of recipients of kidney transplants experiencing
      antibody-mediated rejection in the absence of donor-specific HLA antibodies. Four
      antigenic targets expressed on endothelial cells were identified: endoglin, Fms
      like tyrosine kinase-3 ligand, EGF-like repeats and discoidin I-like domains 3,
      and intercellular adhesion molecule 4; the first three have been implicated in
      endothelial cell activation and leukocyte extravasation. To validate these
      findings, ELISAs were constructed, and sera from an additional 150 renal
      recipients were tested. All four AECAs were detected in 24% of pretransplant
      sera, and they were associated with post-transplant donor-specific HLA
      antibodies, antibody-mediated rejection, and early transplant glomerulopathy.
      AECA stimulation of endothelial cell cultures increased adhesion molecule
      expression and production of inflammatory cytokines: regulated on activation,
      normal T cell expressed and secreted PDGF and RESISTIN. These correlations
      between in vitro experiments and in vivo histopathology suggest that AECAs
      activate the vascular endothelium, amplifying the alloimmune response and
      increasing microvascular damage. Given the growing number of transplant
      candidates, a better understanding of the antigenic targets, beyond HLA, and
      mechanisms of immune injury will be essential for improving long-term allograft
      survival. 

PMID- 25381427
TI  - Isolated endarteritis and kidney transplant survival: a multicenter collaborative
      study.
AB  - Isolated endarteritis of kidney transplants is increasingly recognized. Notably,
      microarray studies revealed absence of immunologic signatures of rejection in
      most isolated endarteritis biopsy samples. We investigated if isolated
      endarteritis responds to rejection treatment and affects kidney transplant
      survival. We retrospectively enrolled recipients of kidney transplant who
      underwent biopsies between 1999 and 2011 at seven American and Canadian centers.
      Exclusion criteria were recipients were blood group-incompatible or crossmatch
      positive or had C4d-positive biopsy samples. After biopsy confirmation, patients
      were divided into three groups: isolated endarteritis (n=103), positive controls
      (type I acute T cell-mediated rejection with endarteritis; n=101), and negative
      controls (no diagnostic rejection; n=103). Primary end points were improved
      kidney function after rejection treatment and transplant failure. Mean decrease
      in serum creatinine from biopsy to 1 month after rejection treatment was 132.6
      umol/L (95% confidence interval [95% CI], 78.7 to 186.5) in patients with
      isolated endarteritis, 96.4 umol/L (95% CI, 48.6 to 143.2) in positive controls
      (P=0.32), and 18.6 umol/L (95% CI, 1.8 to 35.4) in untreated negative controls
      (P<0.001). Functional improvement after rejection treatment occurred in 80% of
      patients with isolated endarteritis and 81% of positive controls (P=0.72). Over
      the median 3.2-year follow-up period, kidney transplant survival rates were 79%
      in patients with isolated endarteritis, 79% in positive controls, and 91% in
      negative controls (P=0.01). In multivariate analysis, isolated endarteritis was
      associated with an adjusted 3.51-fold (95% CI, 1.16 to 10.67; P=0.03) risk for
      transplant failure. These data indicate that isolated endarteritis is an
      independent risk factor for kidney transplant failure. 

PMID- 25381428
TI  - Renal allograft rejection: pieces of the puzzle.

PMID- 25381432
TI  - Genetic variation in a grapevine progeny (Vitis vinifera L. cvs Grenache*Syrah)
      reveals inconsistencies between maintenance of daytime leaf water potential and
      response of transpiration rate under drought.
AB  - In the face of water stress, plants evolved with different abilities to limit the
      decrease in leaf water potential, notably in the daytime (PsiM). So-called
      isohydric species efficiently maintain high PsiM, whereas anisohydric species
      cannot prevent PsiM from dropping as soil water deficit develops. The genetic and
      physiological origins of these differences in (an)isohydric behaviours remain to
      be clarified. This is of particular interest within species such as Vitis
      vinifera L. where continuous variation in the level of isohydry has been observed
      among cultivars. With this objective, a 2 year experiment was conducted on the
      pseudo-F1 progeny from a cross between the two widespread cultivars Syrah and
      Grenache using a phenotyping platform coupled to a controlled-environment
      chamber. Potted plants of all the progeny were analysed for PsiM, transpiration
      rate, and soil-to-leaf hydraulic conductance, under both well-watered and water
      deficit conditions. A high genetic variability was found for all the above
      traits. Four quantitative trait loci (QTLs) were detected for PsiM under water
      deficit conditions, and 28 other QTLs were detected for the different traits in
      either condition. Genetic variation in PsiM maintenance under water deficit
      weakly correlated with drought-induced reduction in transpiration rate in the
      progeny, and QTLs for both traits did not completely co-localize. This indicates
      that genetic variation in the control of PsiM under water deficit was not due
      simply to variation in transpiration sensitivity to soil drying. Possible origins
      of the diversity in (an)isohydric behaviours in grapevine are discussed on the
      basis of concurrent variations in soil-to-leaf hydraulic conductance and stomatal
      control of transpiration. 

PMID- 25381433
TI  - Drought adaptation of stay-green sorghum is associated with canopy development,
      leaf anatomy, root growth, and water uptake.
AB  - Stay-green sorghum plants exhibit greener leaves and stems during the grain
      filling period under water-limited conditions compared with their senescent
      counterparts, resulting in increased grain yield, grain mass, and lodging
      resistance. Stay-green has been mapped to a number of key chromosomal regions,
      including Stg1, Stg2, Stg3, and Stg4, but the functions of these individual
      quantitative trait loci (QTLs) remain unclear. The objective of this study was to
      show how positive effects of Stg QTLs on grain yield under drought can be
      explained as emergent consequences of their effects on temporal and spatial water
      use patterns that result from changes in leaf-area dynamics. A set of four Stg
      near-isogenic lines (NILs) and their recurrent parent were grown in a range of
      field and semicontrolled experiments in southeast Queensland, Australia. These
      studies showed that the four Stg QTLs regulate canopy size by: (1) reducing
      tillering via increased size of lower leaves, (2) constraining the size of the
      upper leaves; and (3) in some cases, decreasing the number of leaves per culm. In
      addition, they variously affect leaf anatomy and root growth. The multiple
      pathways by which Stg QTLs modulate canopy development can result in considerable
      developmental plasticity. The reduction in canopy size associated with Stg QTLs
      reduced pre-flowering water demand, thereby increasing water availability during
      grain filling and, ultimately, grain yield. The generic physiological mechanisms
      underlying the stay-green trait suggest that similar Stg QTLs could enhance post
      anthesis drought adaptation in other major cereals such as maize, wheat, and
      rice. 

PMID- 25381434
TI  - The thymic microenvironment differentially regulates development and trafficking
      of invariant NKT cell sublineages.
AB  - The regulatory role of the thymic microenvironment during trafficking and
      differentiation of the invariant NKT (iNKT) cell lineage remains poorly
      understood. In this study, we show that fractalkine receptor expression marks
      emigrating subpopulations of the NKT1, NKT2, and NKT17 sublineages in the thymus
      and peripheral organs of naive mice. Moreover, NKT1 sublineage cells can be
      subdivided into two subsets, namely NKT1(a) and NKT1(b), which exhibit distinct
      developmental and tissue-specific distribution profiles. More specifically,
      development and trafficking of the NKT1(a) subset are selectively dependent upon
      lymphotoxin (LT)alpha1beta2-LTbeta receptor-dependent differentiation of thymic
      stroma, whereas the NKT1(b), NKT2, and NKT17 sublineages are not. Furthermore, we
      identify a potential cellular source for LTalpha1beta2 during thymic
      organogenesis, marked by expression of IL-7Ralpha, which promotes differentiation
      of the NKT1(a) subset in a noncell-autonomous manner. Collectively, we propose a
      mechanism by which thymic differentiation and retention of the NKT1 sublineage
      are developmentally coupled to LTalpha1beta2-LTbeta receptor-dependent thymic
      organogenesis. 

PMID- 25381435
TI  - TCR signaling events are required for maintaining CD4 regulatory T cell numbers
      and suppressive capacities in the periphery.
AB  - CD4 regulatory T cells (Tregs) can be subdivided into two subsets according to Ly
      6C expression in the periphery. Phenotypic analysis, imaging, and adoptive
      transfer experiments of peripheral Ly-6C(-) and Ly-6C(+) Tregs reveal that the
      nonexpression of Ly-6C by ~70% of peripheral Tregs depends on TCR signaling
      events. Interestingly, Ly-6C(-) Tregs express higher surface amounts of key
      immunosuppressive molecules than do Ly-6C(+) Tregs and produce constitutively
      anti-inflammatory cytokines. In line with their phenotype, Ly-6C(+) Tregs exhibit
      poor suppressive capacities in vitro and in vivo. Finally, although Ly-6C(-)
      Tregs maintain their numbers with age, Ly-6C(+) Tregs gradually disappear.
      Altogether, our data strongly suggest that both the survival and suppressive
      functions of peripheral CD4 Tregs rely on their ability to receive strong TCR
      signals. 

PMID- 25381429
TI  - Rituximab versus cyclophosphamide for ANCA-associated vasculitis with renal
      involvement.
AB  - Rituximab (RTX) is non-inferior to cyclophosphamide (CYC) followed by
      azathioprine (AZA) for remission-induction in severe ANCA-associated vasculitis
      (AAV), but renal outcomes are unknown. This is a post hoc analysis of patients
      enrolled in the Rituximab for ANCA-Associated Vasculitis (RAVE) Trial who had
      renal involvement (biopsy proven pauci-immune GN, red blood cell casts in the
      urine, and/or a rise in serum creatinine concentration attributed to vasculitis).
      Remission-induction regimens were RTX at 375 mg/m(2) * 4 or CYC at 2 mg/kg/d. CYC
      was replaced by AZA (2 mg/kg/d) after 3-6 months. Both groups received
      glucocorticoids. Complete remission (CR) was defined as Birmingham Vasculitis
      Activity Score/Wegener's Granulomatosis (BVAS/WG)=0 off prednisone. Fifty-two
      percent (102 of 197) of the patients had renal involvement at entry. Of these
      patients, 51 were randomized to RTX, and 51 to CYC/AZA. Mean eGFR was lower in
      the RTX group (41 versus 50 ml/min per 1.73 m(2); P=0.05); 61% and 75% of
      patients treated with RTX and 63% and 76% of patients treated with CYC/AZA
      achieved CR by 6 and 18 months, respectively. No differences in remission rates
      or increases in eGFR at 18 months were evident when analysis was stratified by
      ANCA type, AAV diagnosis (granulomatosis with polyangiitis versus microscopic
      polyangiitis), or new diagnosis (versus relapsing disease) at entry. There were
      no differences between treatment groups in relapses at 6, 12, or 18 months. No
      differences in adverse events were observed. In conclusion, patients with AAV and
      renal involvement respond similarly to remission induction with RTX plus
      glucocorticoids or CYC plus glucocorticoids. 

PMID- 25381436
TI  - The extracellular adherence protein from Staphylococcus aureus inhibits the
      classical and lectin pathways of complement by blocking formation of the C3
      proconvertase.
AB  - The pathogenic bacterium Staphylococcus aureus actively evades many aspects of
      human innate immunity by expressing a series of small inhibitory proteins. A
      number of these proteins inhibit the complement system, which labels bacteria for
      phagocytosis and generates inflammatory chemoattractants. Although the majority
      of staphylococcal complement inhibitors act on the alternative pathway to block
      the amplification loop, only a few proteins act on the initial recognition
      cascades that constitute the classical pathway (CP) and lectin pathway (LP). We
      screened a collection of recombinant, secreted staphylococcal proteins to
      determine whether S. aureus produces other molecules that inhibit the CP and/or
      LP. Using this approach, we identified the extracellular adherence protein (Eap)
      as a potent, specific inhibitor of both the CP and LP. We found that Eap blocked
      CP/LP-dependent activation of C3, but not C4, and that Eap likewise inhibited
      deposition of C3b on the surface of S. aureus cells. In turn, this significantly
      diminished the extent of S. aureus opsonophagocytosis and killing by neutrophils.
      This combination of functional properties suggested that Eap acts specifically at
      the level of the CP/LP C3 convertase (C4b2a). Indeed, we demonstrated a direct,
      nanomolar-affinity interaction of Eap with C4b. Eap binding to C4b inhibited
      binding of both full-length C2 and its C2b fragment, which indicated that Eap
      disrupts formation of the CP/LP C3 proconvertase (C4b2). As a whole, our results
      demonstrate that S. aureus inhibits two initiation routes of complement by
      expression of the Eap protein, and thereby define a novel mechanism of immune
      evasion. 

PMID- 25381438
TI  - Notch3 activation is sufficient but not required for inducing human T-lineage
      specification.
AB  - Although the role for the individual Notch receptors in early hematopoiesis have
      been thoroughly investigated in mouse, studies in human have been mostly limited
      to the use of pan-Notch inhibitors. However, such studies in human are important
      to predict potential side effects of specific Notch receptor blocking reagents
      because these are currently being considered as therapeutic tools to treat
      various Notch-dependent diseases. In this study, we studied the individual roles
      of Notch1 and Notch3 in early human hematopoietic lineage decisions, particularly
      during T-lineage specification. Although this process in mice is solely dependent
      on Notch1 activation, we recently reported Notch3 expression in human uncommitted
      thymocytes, raising the possibility that Notch3 mediates human T-lineage
      specification. Although expression of a constitutive activated form of Notch3
      (ICN3) results in the induction of T-lineage specification in human CD34(+)
      hematopoietic progenitor cells, similar to ICN1 overexpression, loss-of-function
      studies using blocking Abs reveal that only Notch1, but not Notch3, is critical
      in this process. Blocking of Notch1 activation in OP9-DLL4 cocultures resulted in
      a complete block in T-lineage specification and induced monocytic and
      plasmacytoid dendritic cell differentiation instead. In fetal thymus organ
      cultures, impeded Notch1 activation resulted in B and dendritic cell development.
      In contrast, Notch3 blocking Abs only marginally affected T-lineage specification
      and hematopoietic differentiation with a slight increase in monocyte development.
      No induction of B or dendritic cell development was observed. Thus, our results
      unambiguously reveal a nonredundant role for Notch1 in human T-lineage
      specification, despite the expression of other Notch receptors. 

PMID- 25381439
TI  - Can children substitute for adult listeners in judging the intelligibility of the
      speech of children who are deaf or hard of hearing?
AB  - PURPOSE: Assessments of the intelligibility of speech produced by children who
      are deaf or hard of hearing (D/HH) provide unique insights into functional
      speaking ability, readiness for mainstream classroom placements, and intervention
      effectiveness. The development of sentence lists for a wide age range of children
      and the advent of handheld digital recording devices have overcome two barriers
      to routine use of this tool. Yet, difficulties in recruiting adequate numbers of
      adults to judge speech samples continue to make routine assessment impractical.
      In response to this barrier, it has been proposed that children who are 9 years
      or older might be adequate substitutes for adult listener-judges (Ertmer, 2011).
      METHOD: To examine this possibility, 22 children from the 3rd, 4th, and 5th
      grades identified words from speech samples previously judged by adults. RESULTS:
      Children in the 3rd and 4th grades identified fewer words than adults, whereas
      scores for 5th graders were not significantly different from those of the adults.
      All grade levels showed increasing scores across low, mid, and high levels of
      intelligibility. CONCLUSIONS: Children who are functioning at a 5th grade level
      or higher can act as listener-judges in speech intelligibility assessments.
      Suggestions for implementing assessments and scoring child-listeners' written
      responses are discussed.

PMID- 25381437
TI  - NK cells with KIR2DS2 immunogenotype have a functional activation advantage to
      efficiently kill glioblastoma and prolong animal survival.
AB  - Glioblastomas (GBMs) are lethal brain cancers that are resistant to current
      therapies. We investigated the cytotoxicity of human allogeneic NK cells against
      patient-derived GBM in vitro and in vivo, as well as mechanisms mediating their
      efficacy. We demonstrate that KIR2DS2 immunogenotype NK cells were more potent
      killers, notwithstanding the absence of inhibitory killer Ig-like receptor (KIR)
      HLA ligand mismatch. FACS-sorted and enriched KIR2DS2(+) NK cell subpopulations
      retained significantly high levels of CD69 and CD16 when in contact with GBM
      cells at a 1:1 ratio and highly expressed CD107a and secreted more soluble CD137
      and granzyme A. In contrast, KIR2DS2(-) immunogenotype donor NK cells were less
      cytotoxic against GBM and K562, and, similar to FACS-sorted or gated KIR2DS2(-)
      NK cells, significantly diminished CD16, CD107a, granzyme A, and CD69 when in
      contact with GBM cells. Furthermore, NK cell-mediated GBM killing in vitro
      depended upon the expression of ligands for the activating receptor NKG2D and was
      partially abrogated by Ab blockade. Treatment of GBM xenografts in NOD/SCID mice
      with NK cells from a KIR2DS2(+) donor lacking inhibitory KIR-HLA ligand mismatch
      significantly prolonged the median survival to 163 d compared with vehicle
      controls (log-rank test, p = 0.0001), in contrast to 117.5 d (log-rank test, p =
      0.0005) for NK cells with several inhibitory KIR-HLA ligand mismatches but
      lacking KIR2DS2 genotype. Significantly more CD56(+)CD16(+) NK cells from a
      KIR2DS2(+) donor survived in nontumor-bearing brains 3 wk after infusion compared
      with KIR2DS2(-) NK cells, independent of their proliferative capacity. In
      conclusion, KIR2DS2 identifies potent alloreactive NK cells against GBM that are
      mediated by commensurate, but dominant, activating signals. 

PMID- 25381440
TI  - The dissociation of video head impulse test (vHIT) and bithermal caloric test
      results provide topological localization of vestibular system impairment in
      patients with "definite" Meniere's disease.
AB  - PURPOSE: We report 3 patients with Meniere's disease and describe how the
      combination of audiometry, video head impulse testing, and caloric results may
      prove helpful in the diagnosis of Meniere's disease. METHOD: Three patients with
      "definite" Meniere's disease were evaluated in a tertiary care medical center.
      Each patient underwent videonystagmography, horizontal canal video head impulse
      testing, and audiometry. RESULTS: All 3 patients demonstrated moderate, flat,
      sensorineural hearing losses; significant caloric asymmetries; and bilaterally
      normal video head impulse testing. This pattern of findings suggests differential
      preservation of high-frequency function (video head impulse testing) with
      impairment of low-frequency function (unilaterally abnormal caloric test results)
      in these patients. CONCLUSION: Ipsilesional abnormal caloric testing in the
      presence of normal video head impulse testing is a pattern of findings observed
      in a cohort of patients who have "definite" Meniere's disease.

PMID- 25381441
TI  - Occupational exposure to chrome VI compounds in French companies: results of a
      national campaign to measure exposure (2010-2013).
AB  - A campaign to measure exposure to hexavalent chromium compounds was carried out
      in France by the seven CARSAT chemistry laboratories, CRAMIF laboratory, and INRS
      over the 2010-2013 period. The survey included 99 companies involved in various
      activity sectors. The inhalable fraction of airborne particles was sampled, and
      exposure levels were determined using ion chromatography analysis combined with
      post-column derivatization and UV detection. The quality of the measurement
      results was guaranteed by an inter-laboratory comparison system involving all the
      laboratories participating in this study. Exposure levels frequently exceeded the
      French occupational exposure limit value (OELV) of 1 ug m(-3), in activities such
      as thermal metallization and manufacturing and application of paint in the
      aeronautics sector. The results also reveal a general trend for a greater
      proportion of soluble Chromium VI (Cr VI) compounds compared with insoluble
      compounds. Qualitative and quantitative information relating to the presence of
      other metallic compounds in the air of workplaces is also provided, for example
      for Cr III, Ni, Fe, etc. The sampling strategy used and the measurement method
      are easy to implement, making it possible to check occupational exposure with a
      view to comparing it to an 8 h-OELV of 1 ug m(-3). 

PMID- 25381442
TI  - Insights into the specificity of lysine acetyltransferases.
AB  - Reversible lysine acetylation by protein acetyltransferases is a conserved
      regulatory mechanism that controls diverse cellular pathways. Gcn5-related N
      acetyltransferases (GNATs), named after their founding member, are found in all
      domains of life. GNATs are known for their role as histone acetyltransferases,
      but non-histone bacterial protein acetytransferases have been identified. Only
      structures of GNAT complexes with short histone peptide substrates are available
      in databases. Given the biological importance of this modification and the
      abundance of lysine in polypeptides, how specificity is attained for larger
      protein substrates is central to understanding acetyl-lysine-regulated networks.
      Here we report the structure of a GNAT in complex with a globular protein
      substrate solved to 1.9 A. GNAT binds the protein substrate with extensive
      surface interactions distinct from those reported for GNAT-peptide complexes. Our
      data reveal determinants needed for the recognition of a protein substrate and
      provide insight into the specificity of GNATs. 

PMID- 25381443
TI  - Thrombin-dependent Incorporation of von Willebrand Factor into a Fibrin Network.
AB  - Attachment of platelets from the circulation onto a growing thrombus is a process
      involving multiple platelet receptors, endothelial matrix components, and
      coagulation factors. It has been indicated previously that during a
      transglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links
      von Willebrand factor (VWF) to polymerizing fibrin. Bound VWF further recruits
      and activates platelets via interactions with the platelet receptor complex
      glycoprotein Ib (GPIb). In the present study we found proof for binding of VWF to
      a fibrin monomer layer during the process of fibrinogen-to-fibrin conversion in
      the presence of thrombin, arvin, or a snake venom from Crotalus atrox. Using a
      domain deletion mutant we demonstrated the involvement of the C domains of VWF in
      this binding. Substantial binding of VWF to fibrin monomers persisted in the
      presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking via
      factor XIII is not essential for this phenomenon and suggesting the
      identification of a second mechanism through which VWF multimers incorporate into
      a fibrin network. Under high shear conditions, platelets were shown to adhere to
      fibrin only if VWF had been incorporated. In conclusion, our experiments show
      that the C domains of VWF and the E domain of fibrin monomers are involved in the
      incorporation of VWF during the polymerization of fibrin and that this
      incorporation fosters binding and activation of platelets. Fibrin thus is not an
      inert end product but partakes in further thrombus growth. Our findings help to
      elucidate the mechanism of thrombus growth and platelet adhesion under conditions
      of arterial shear rate. 

PMID- 25381444
TI  - The nasomaxillary complex and the cranial base in artificial cranial deformation:
      relationships from a geometric morphometric study.
AB  - INTRODUCTION: It is widely accepted that there is a relationship between the
      cranial base and the development of the nasomaxillary complex (NMC). The
      objective of the present study was to investigate the morphological relationship
      between these two anatomical units in skulls that have intentionally been
      subjected to one of two types of artificial deformity of the cranial vault
      [artificially deformed skulls (ADS)]. MATERIAL AND METHODS: A geometric
      morphometry study was performed on lateral cephalometric X-rays of three groups
      of crania: 32 with anteroposterior (AP) deformity, 17 with circumferential (C)
      deformity, and 39 with no apparent deformity. RESULTS: The cranial base of the
      ADS showed marked deformity that produced a restriction of AP growth of the NMC,
      alterations of the roof of the orbit as a consequence of the rotation of anterior
      cranial fossa, and nasal protrusion. Pronounced morphological differences were
      found between the three groups: increased vertical development of the maxilla
      occurred in both ADS groups due to growth of the alveolar process, and rotation
      of the maxilla and displacement of the orbital rim was observed in the C group.
      This confirms that the posterior facial plane is regarded as an axial structure
      that serves as an interface between the middle cranial base and the NMC (Enlow,
      D.H. and Hans, M.G. (1996) Essential of Facial Growth. WB Saunders Co.,
      Philadelphia, PA). LIMITATIONS: It is important to take into account that these
      results have been obtained from an archaeological sample, with all the
      limitations that this implies such as being a small sample and with no absolute
      certainty regarding the use of the same type of deforming device within each
      group. Furthermore, this is a lateral two-dimensional study in which transverse
      development has not been analysed. CONCLUSIONS: Artificial modification of the
      shape of the vault has repercussions on the NMC that support the theory of an all
      inclusive integration of the different cranial units in normal as well as in
      restricted development.

PMID- 25381445
TI  - An analysis of residual orthodontic treatment need in municipal health centres.
AB  - OBJECTIVE: The aim of this study was to analyse residual orthodontic treatment
      need in Finnish municipal health centres. SUBJECTS AND METHODS: A random sample
      of two age groups, 16- and 18-year-olds (n = 2212), from seven municipalities was
      invited for a clinical examination, and 1041 adolescents participated. Two
      calibrated orthodontists blindly examined the participants for residual treatment
      need, applying the Dental Health Component (DHC) and Aesthetic Component (AC) of
      the Index of Orthodontic Treatment Need. Self-perceived treatment need,
      satisfaction with occlusal function, and dental appearance were evaluated with a
      questionnaire. Differences between objective and self-perceived treatment need
      and between treated and untreated adolescents were analysed using the chi-square
      test. RESULTS: A total of 18.8 per cent of all adolescents had DHC grade 4 or 5
      and/or AC category 8-10, indicating a definite need for treatment. In the
      analysis between treated and untreated adolescents, orthodontic treatment history
      or gender had no statistically significant association with the objectively
      defined need (P > 0.05). Self-perceived treatment need was reported by 9.6 per
      cent of adolescents. This need was more common among treated (13.9 per cent) than
      untreated (4.6 per cent) adolescents (P < 0.001). Among all adolescents,
      satisfaction with occlusal function was high, 91.3 per cent; 78.9 per cent of
      adolescents were satisfied with their dental appearance. The main reasons for
      dissatisfaction and self-perceived need were visible contact point displacements.
      CONCLUSIONS: The observed proportion of residual orthodontic treatment need is in
      line with earlier findings. The high satisfaction with occlusal function reflects
      the applied selection criteria; orthodontic treatment of displacements causing
      only aesthetic concern is not prioritized.

PMID- 25381446
TI  - Teaching active listening skills to pre-service speech-language pathologists: a
      first step in supporting collaboration with parents of young children who require
      AAC.
AB  - PURPOSE: This study examined the effect of instruction in an active listening
      strategy on the communication skills of pre-service speech-language pathologists
      (SLPs). METHOD: Twenty-three pre-service SLPs in their 2nd year of graduate study
      received a brief strategy instruction in active listening skills. Participants
      were videotaped during a simulated parent meeting before and after the strategy
      instruction. Simulated parent meetings addressed issues that parents of children
      who use augmentative and alternative communication (AAC) may face. Social
      validity measures were gathered from the participants and from parents of
      children who use AAC. RESULTS: Pre- and postinstruction use of the active
      listening strategy was scored and compared using a Wilcoxon signed-ranks test,
      with statistically significant results. Postinstruction scores were significantly
      higher than preinstruction scores, providing evidence of the effectiveness of the
      instruction. Furthermore, participants and parents of children who use AAC
      described the postinstruction interactions more positively than the
      preinstruction interactions, suggesting that the pre-service SLPs benefited from
      the instruction. CONCLUSION: The current study provides evidence of the
      effectiveness of strategy instruction in active listening skills that may be
      incorporated into SLP preparation programs.

PMID- 25381447
TI  - Monolingual or bilingual intervention for primary language impairment? A
      randomized control trial.
AB  - PURPOSE: This study investigated the clinical effectiveness of monolingual versus
      bilingual language intervention, the latter involving speech-language pathologist
      parent collaboration. The study focuses on methods that are currently being
      recommended and that are feasible within current clinical contexts. METHOD:
      Bilingual children with primary language impairment who speak a minority language
      as their home language and French as their second (n=29, mean age=5 years) were
      randomly assigned to monolingual treatment, bilingual treatment, and no-treatment
      (delayed-treatment) conditions. Sixteen sessions of individual language
      intervention were offered, targeting vocabulary and syntactic skills in French
      only or bilingually, through parent collaboration during the clinical sessions.
      Language evaluations were conducted before and after treatment by blinded
      examiners; these evaluations targeted French as well as the home languages. An
      additional evaluation was conducted 2 months after completion of treatment to
      assess maintenance of gains. Both monolingual and bilingual treatment followed a
      focused stimulation approach. RESULTS: Results in French showed a significant
      treatment effect for vocabulary but no difference between treatment conditions.
      Gains were made in syntax, but these gains could not be attributed to treatment
      given that treatment groups did not improve more than the control group. Home
      language probes did not suggest that the therapy had resulted in gains in the
      home language. CONCLUSIONS: The intervention used in this study is in line with
      current recommendations of major speech-language pathology organizations.
      However, the findings indicate that the bilingual treatment created through
      collaboration with parents was not effective in creating a sufficiently intense
      bilingual context to make it significantly different from the monolingual
      treatment. Further studies are needed to assess the gains associated with
      clinical modifications made for bilingual children and to search for effective
      ways to accommodate their unique needs.

PMID- 25381448
TI  - Hyperimmune bovine colostrum as a novel therapy to combat Clostridium difficile
      infection.
AB  - BACKGROUND: Clostridium difficile is a primary cause of antibiotic-associated
      diarrhea that typically develops when gut microbiota is altered. Conventional
      treatment for C. difficile infection (CDI) is additional antimicrobial
      administration, which further disrupts normal intestinal microbiota, often
      resulting in poor treatment outcomes. METHODS: A pregnant dairy cow was
      repeatedly immunized with recombinant mutants of toxins A and B produced by C.
      difficile, and the resultant hyperimmune bovine colostrum (HBC) was evaluated for
      therapeutic efficacy in gnotobiotic piglets with diarrhea due to CDI. Control
      piglets received nonimmune colostrum. To determine the impact of HBC on gut
      microbiota, 1 of 2 groups of piglets transplanted with normal human gut
      microbiota was treated with HBC. RESULTS: Nonimmune colostrum-treated piglets
      developed moderate to severe diarrhea and colitis. In contrast, HBC-treated
      piglets had mild or no diarrhea and mild or no colitis. Lyophilization had no
      detectable impact on HBC efficacy. HBC had no discernible effect on the
      composition of normal human gut microbiota in the porcine intestinal tract.
      CONCLUSIONS: HBC provides an oral, cost-effective, and safe alternative to
      antibiotic therapy for CDI. By preserving intestinal microbiota, HBC may be more
      efficacious than antibiotics. Additional studies are warranted to establish HBC
      as a viable immunotherapeutic agent for human use against CDI.

PMID- 25381451
TI  - Comment on 'protein-protein binding affinity prediction from amino acid
      sequence'.

PMID- 25381449
TI  - Ten-year follow-up of the OPUS specialized early intervention trial for patients
      with a first episode of psychosis.
AB  - INTRODUCTION: Specialized early intervention programs such as The Danish OPUS
      treatment are efficient in treating patients with a first episode of psychosis
      (FEP) at least after 2 and 5 years. Few studies have examined long-term outcomes
      of these interventions. AIM: To examine the effect of 2 years of OPUS vs
      treatment as usual (TAU) within an FEP cohort, 10 years after inclusion into the
      OPUS trial. METHODS: From 1998 to 2000, participants were randomized to OPUS or
      TAU. Ten years later, we conducted comprehensive interviews and performed
      register-based follow-up on all participants in national Danish registers. We
      analyzed participants according to the intention-to-treat principle. RESULTS: Of
      the 547 participants included in the study, 347 (63.4%) took part in this follow
      up. While there was evidence of a differential 10-year course in the development
      of negative symptoms, psychiatric bed days, and possibly psychotic symptoms in
      favor of OPUS treatment, differences were driven by effects at earlier follow-ups
      and had diminished over time. Statistically significant differences in the course
      of use of supported housing were present even after 8-10 years. There were no
      differences between OPUS and TAU regarding income, work-related outcomes, or
      marital status. CONCLUSION: Most of the positive short-term effects of the OPUS
      intervention had diminished or vanished at this long-term follow-up. We observed
      a clear tendency that OPUS treatment leads to fewer days in supported housing.
      There is a need for further studies investigating if extending the intervention
      will improve outcomes more markedly at long-term follow-ups.

PMID- 25381450
TI  - Consequences of co-occurring attention-deficit/hyperactivity disorder on
      children's language impairments.
AB  - PURPOSE: Co-occurring attention-deficit/hyperactivity disorder (ADHD) and
      communication disorders represent a frequently encountered challenge for school
      based practitioners. The purpose of the present study was to examine in more
      detail the clinical phenomenology of co-occurring ADHD and language impairments
      (LIs). METHOD: Measures of nonword repetition, sentence recall, and tense marking
      were collected from 57 seven- to nine-year-old children. The performances of
      children with ADHD+LI status were compared with those of children with specific
      language impairment (SLI) and children with typical development (TD). RESULTS:
      ADHD status had no independent detrimental impact on the affected children's LIs
      (SLI = ADHD+LI < TD). A modest positive correlation was found between the
      severity of children's ADHD symptoms and their sentence recall performance,
      suggesting a tendency for affected children who had higher levels of ADHD
      symptoms to perform better than those children with lower levels. CONCLUSION:
      These outcomes are difficult to reconcile with attention-deficit/information
      processing accounts of the core deficits associated with SLI. Potential
      protective mechanisms associated with ADHD status are discussed.

PMID- 25381452
TI  - The science of clinical geropsychology.

PMID- 25381453
TI  - Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal
      adenocarcinoma: the influence of Helicobacter pylori infection status.
AB  - Cell free circulating microRNAs (cfmiRNAs) have been recognized as robust and
      stable biomarkers of cancers. However, little is known about the prognostic
      significance of cfmiRNAs in esophageal adenocarcinoma (EA). In this study, we
      explored whether specific cfmiRNA profiles could predict EA prognosis and whether
      Helicobacter pylori (HP) infection status could influence the association between
      cfmiRNAs and EA survival outcome. We profiled 1075 miRNAs in pooled serum samples
      from 30 EA patients and 30 healthy controls. The most relevant cfmiRNAs were then
      assessed for their associations with EA survival in an independent cohort of 82
      patients, using Log-rank test and multivariate Cox regression models.
      Quantitative real-time PCR (qRT-PCR) was used for cfmiRNA profiling. HP infection
      status was determined by immunoblotting assay. We identified a panel of 18
      cfmiRNAs that could distinguish EA patients from healthy subjects (P = 3.0E-12).
      In overall analysis and in HP-positive subtype patients, no cfmiRNA was
      significantly associated with EA prognosis. In HP-negative patients, however, 15
      cfmiRNAs were significantly associated with overall survival (OS) (all P < 0.05).
      A combined 2-cfmiRNA (low miR-3935 and high miR-4286) risk score was constructed;
      that showed greater risk for worse OS (HR = 2.22, P = 0.0019) than individual
      cfmiRNA alone. Patients with high-risk score had >10-fold increased risk of death
      than patients with low risk score (P = 0.0302; HR = 10.91; P = 0.0094). Our
      findings suggest that dysregulated cfmiRNAs may contribute to EA survival outcome
      and HP infection status may modify the association between cfmiRNAs and EA
      survival. 

PMID- 25381455
TI  - Long-term evaluation of bulking agents for the treatment of fecal incontinence:
      clinical outcomes and ultrasound evidence.
AB  - BACKGROUND: The injection of bulking agents into the anal canal has been reported
      to help patients with fecal incontinence. Although it has been advocated as a
      safe and effective option, substantial data concerning long-term efficacy are
      still lacking, and the resorption process of the implants has not yet been
      carefully studied. The aim of our study was to investigate the long-term outcomes
      of bulking agents for the treatment of fecal incontinence and the behavior of
      implanted materials in the anorectum. METHODS: At a median follow-up of 7 years,
      19 patients with idiopathic fecal incontinence who had received bulking agent
      implants were evaluated. Clinical, manometric and ultrasound assessments were
      carried out. RESULTS: The clinical improvements that were achieved in the short
      term were not maintained over time. For each patient, the number of implants that
      could no longer be identified on ultrasound was significantly correlated with
      poorer clinical long-term outcomes. On average, only 14% of the originally
      injected volume was still detectable. CONCLUSIONS: In the long term, perianally
      injected bulking agents seem to lose effectiveness. The ultrasound assessment
      suggests that the process of resorption is almost complete, and the implants are
      no longer effective in treating incontinence.

PMID- 25381456
TI  - Abnormalities in collagen composition may contribute to the pathogenesis of
      hemorrhoids: morphometric analysis.
AB  - PURPOSE: While hemorrhoidal disease is common, its etiology remains unclear. It
      has been postulated that disturbances in collagen lead to reduced connective
      tissue stability, and in turn to the development of hemorrhoidal disease. We
      aimed to compare the quality and quantity of collagen in patients with
      hemorrhoidal disease versus normal controls. METHODS: Specimens from 57 patients
      with grade III or IV internal hemorrhoids undergoing hemorrhoidectomy between
      2006 and 2011 were evaluated. Samples from 20 human cadavers without hemorrhoidal
      disease served as controls. Quality of collagen was analyzed by collagen I/III
      ratio, and quantity of collagen was determined by collagen/protein ratio. The
      study group was subdivided into gender and age subgroups. RESULTS: The
      male:female ratios in the study and control groups were 30:27 and 10:10,
      respectively. Median age was significantly less in the study group [46.9 years
      (range 20-69)] compared to the control group [76 years (range 46-90)] with P <
      0.05. Tissues from patients in the study group had significantly lower collagen
      I/III ratio as compared to the control group (4.4 +/- 1.1 vs. 5.5 +/- 0.6; P <
      0.0001). Nevertheless, despite a trend toward lower collagen/protein ratio in the
      study group, it did not reach statistical significance (57 +/- 42.4 vs. 73 +/-
      32.5 g/mg; P = 0.167). There was no difference in collagen I/III or
      collagen/protein ratios among different age groups and genders. CONCLUSIONS:
      Hemorrhoidal tissues from patients with hemorrhoidal disease appear to have
      reduced mechanical stability as compared to normal controls.

PMID- 25381457
TI  - Compensatory eye and head movements of patients with homonymous hemianopia in the
      naturalistic setting of a driving simulation.
AB  - Homonymous hemianopia (HH) is a frequent deficit resulting from lesions to post
      chiasmal brain structures with a significant negative impact on activities of
      daily living. To address the question how patients with HH may compensate their
      visual field defect in a naturalistic environment, we performed a driving
      simulation experiment and quantitatively analyzed both eye and head movements
      using a head-mounted pupil camera. 14 patients with HH and 14 matched healthy
      control subjects participated in the study. Based on the detection performance of
      dynamically moving obstacles, which appeared unexpectedly along the sides of the
      road track, we divided the patient group into a high- and a low-performance
      group. Then, we compared parameters of eye and head movements between the two
      patient groups and the matched healthy control group to identify those which
      mediate successful detection of potentially hazardous objects. Differences in
      detection rates could not be explained by demographic variables or the extent of
      the visual field defect. Instead, high performance of patients with HH in the
      naturalistic setting of our driving simulation depended on an adapted visual
      exploratory behavior characterized by a relative increase in the amplitude and a
      corresponding increase in the peak velocity of saccades, widening horizontally
      the distribution of eye movements, and by a shift of the overall distribution of
      saccades into the blind hemifield. The result of the group comparison analyses
      was confirmed by a subsequent stepwise regression analysis which identified the
      horizontal spread of eye movements as single factor predicting the detection of
      hazardous objects. 

PMID- 25381458
TI  - Radiologic MS disease activity during natalizumab treatment interruption:
      findings from RESTORE.
AB  - The objective of this study is to characterize the timing and extent of
      radiologic MS disease recurrence during the 24-week natalizumab treatment
      interruption period in RESTORE. RESTORE was a randomized, partially placebo
      controlled exploratory study. Natalizumab-treated patients with no gadolinium
      enhancing (Gd+) lesions at screening (n = 175) were randomized 1:1:2 to continue
      natalizumab (n = 45), switch to placebo (n = 42), or switch to other therapies (n
      = 88) for 24 weeks. MRI assessments were performed every 4 weeks. Predictors of
      increased numbers of Gd+ lesions during natalizumab treatment interruption were
      evaluated. The numbers of Gd+ lesions were compared with retrospectively
      collected pre-natalizumab MRI reports and data from placebo-treated patients from
      two historical randomized clinical trials. Gd+ lesions were detected in 0 %
      (0/45) of natalizumab patients, 61 % (25/41) of placebo patients, and 48 %
      (39/81) of other-therapies patients during the randomized treatment period. Gd+
      lesions were detected starting at week 12; most were observed at week 16 or
      later. Thirteen percent (14/107) of patients had >5 Gd+ lesions on >=1 (of 6)
      scans during the randomized treatment period versus 7 % (7/107) of patients pre
      natalizumab (based on medical record of a single scan). Younger patients and
      those with more Gd+ lesions pre-natalizumab were more likely to have increased
      MRI activity. Distribution of total and persistent Gd+ lesions in RESTORE
      patients was similar to placebo-treated historical control patients. In most
      patients, recurring radiological disease activity during natalizumab interruption
      did not exceed pre-natalizumab levels or levels seen in historical control
      patients.

PMID- 25381459
TI  - Stability of auditory event-related potentials in coma research.
AB  - Patients with unresponsive wakefulness syndrome (UWS) or in minimally conscious
      state (MCS) after brain injury show significant fluctuations in their behavioural
      abilities over time. As the importance of event-related potentials (ERPs) in the
      detection of traces of consciousness increases, we investigated the retest
      reliability of ERPs with repeated tests at four different time points. Twelve
      healthy controls and 12 inpatients (8 UWS, 4 MCS; 6 traumatic, 6 non-traumatic)
      were tested twice a day (morning, afternoon) for 2 days with an auditory oddball
      task. ERPs were recorded with a 256-channel-EEG system, and correlated with
      behavioural test scores in the Coma Recovery Scale-revised (CRS-R). The number of
      identifiable P300 responses varied between zero and four in both groups.
      Reliabilities varied between Krippendorff's alpha = 0.43 for within-day
      comparison, and alpha = 0.25 for between-day comparison in the patient group.
      Retest reliability was strong for the CRS-R scores for all comparisons (alpha =
      0.83-0.95). The stability of auditory information processing in patients with
      disorders of consciousness is the basis for other, even more demanding tasks and
      cognitive potentials. The relatively low ERP-retest reliability suggests that it
      is necessary to perform repeated tests, especially when probing for consciousness
      with ERPs. A single negative ERP test result may be mistaken for proof that a UWS
      patient truly is unresponsive.

PMID- 25381461
TI  - The impact of subthalamic deep brain stimulation on caregivers of Parkinson's
      disease patients: an exploratory study.
AB  - To study the caregivers' perception of their own well-being 1 year after
      subthalamic deep brain stimulation (STN-DBS) surgery in Parkinson's disease (PD)
      patients, using a qualitative and quantitative approach. 25 patients and
      caregivers, living together in partnerships, were examined before and at 3-month
      and 1-year follow-up (FU) after STN-DBS surgery. Semi-structured FU interviews
      concerning caregivers' own well-being under STN-DBS were conducted and analyzed:
      caregivers were accordingly assigned to positive or negative outcome groups.
      Quality of life (QoL), depression, apathy and anxiety of caregivers and patients
      were measured. These quantitative data were compared to the 1-year FU interview
      outcomes. Multiple comparisons analyzed caregiver group assignments based on
      these measurements. Logistic regression was used to find predictors.
      Additionally, patients' mood ratings were used in multiple comparisons with
      caregivers' subjective outcome, to analyze the interaction of patient and
      caregiver ratings. At 3-month FU, caregivers were more indecisive concerning
      their own well-being than at 1-year FU. At 1-year FU, caregivers from the
      negative group had greater depression, anxiety and lower QoL ratings. They were
      significantly older compared to the positive group. Patients' depression showed
      significantly stronger improvement in the positive outcome group. Patients'
      apathy and depression ratings were significant covariates of caregivers' QoL. Our
      results show that at 1-year FU over 50 % of the caregivers rated their subjective
      well-being as negative. Especially older and more depressed caregivers are at
      risk. These caregivers and their partners should be monitored more closely to
      identify possible problems and help them adapt following surgery.

PMID- 25381462
TI  - In situ effects of pesticides on amphibians in the Sierra Nevada.
AB  - For more than 20 years, conservationists have agreed that amphibian populations
      around the world are declining. Results obtained through laboratory or mesocosm
      studies and measurement of contaminant concentrations in areas experiencing
      declines have supported a role of contaminants in these declines. The current
      study examines the effects of contaminant exposure to amphibians in situ in areas
      actually experiencing declines. Early larval Pseudacris regilla were translocated
      among Lassen Volcanic, Yosemite and Sequoia National Parks, California, USA and
      caged in wetlands in 2001 and 2002 until metamorphosis. Twenty contaminants were
      identified in tadpoles with an average of 1.3-5.9 (maximum = 10) contaminants per
      animal. Sequoia National Park, which had the greatest variety and concentrations
      of contaminants in 2001, also had tadpoles that experienced the greatest
      mortality, slowest developmental rates and lowest cholinesterase activities.
      Yosemite and Sequoia tadpoles and metamorphs had greater genotoxicity than those
      in Lassen during 2001, as determined by flow cytometry. In 2001 tadpoles at
      Yosemite had a significantly higher rate of malformations, characterized as
      hemimelia (shortened femurs), than those at the other two parks but no
      significant differences were observed in 2002. Fewer differences in contaminant
      types and concentrations existed among parks during 2002 compared to 2001. In
      2002 Sequoia tadpoles had higher mortality and slower developmental rates but
      there was no difference among parks in cholinesterase activities. Although
      concentrations of most contaminants were below known lethal concentrations,
      simultaneous exposure to multiple chemicals and other stressors may have resulted
      in lethal and sublethal effects. 

PMID- 25381460
TI  - Ancillary investigations to diagnose parkinsonism: a prospective clinical study.
AB  - Various ancillary investigations can assist clinicians in the differential
      diagnosis of patients with parkinsonism. It is unknown which test offers greatest
      diagnostic value in clinical practice. We included 156 consecutive patients with
      parkinsonism, but with an initially uncertain diagnosis. At baseline, all
      patients underwent extensive clinical testing and the following ancillary
      investigations: brain magnetic resonance imaging (MRI); (123)I-iodobenzamide
      single photon-emission computed tomography (IBZM-SPECT); analysis of
      cerebrospinal fluid (CSF); and anal sphincter electromyography (EMG). The final
      diagnosis was established after 3-year follow-up by two movement disorder
      specialists, according to international consensus criteria. We determined the
      diagnostic value by comparing the baseline clinical parameters and ancillary
      studies with the final diagnosis. Out of a potential 138 parameters, univariate
      analysis identified 35 parameters that discriminated Parkinson's disease (PD, n =
      62) and atypical parkinsonism (AP, n = 94), with AUC of 0.55-0.81. Stepwise
      logistic regression showed that the combination of tandem gait, axial UPDRS
      subscore, slow saccadic eye movements and dysphagia yielded an AUC of 0.93,
      adjusted for optimism. The combination of tandem gait and axial UDPRS subscore
      yielded an AUC of 0.90. None of the ancillary investigations alone or in
      combination with clinical testing improved this clinically based diagnostic
      accuracy, not even in a subgroup of patients with the greatest diagnostic
      uncertainty at baseline. Our study demonstrates that a comprehensive set of
      clinical tests provides good accuracy to differentiate PD from AP. Our results
      also suggest that routine MRI, IBZM-SPECT, CSF analysis and anal sphincter EMG do
      not improve this diagnostic accuracy. Future work should evaluate the possible
      diagnostic value of more advanced diagnostic tests. 

PMID- 25381463
TI  - The ascending median raphe projections are mainly glutamatergic in the mouse
      forebrain.
AB  - The median raphe region (MRR) is thought to be serotonergic and plays an
      important role in the regulation of many cognitive functions. In the hippocampus
      (HIPP), the MRR exerts a fast excitatory control, partially through glutamatergic
      transmission, on a subpopulation of GABAergic interneurons that are key
      regulators of local network activity. However, not all receptors of this
      connection in the HIPP and in synapses established by MRR in other brain areas
      are known. Using combined anterograde tracing and immunogold methods, we show
      that the GluN2A subunit of the NMDA receptor is present in the synapses
      established by MRR not only in the HIPP, but also in the medial septum (MS) and
      in the medial prefrontal cortex (mPFC) of the mouse. We estimated similar amounts
      of NMDA receptors in these synapses established by the MRR and in local adjacent
      excitatory synapses. Using retrograde tracing and confocal laser scanning
      microscopy, we found that the majority of the projecting cells of the mouse MRR
      contain the vesicular glutamate transporter type 3 (vGluT3). Furthermore, using
      double retrograde tracing, we found that single cells of the MRR can innervate
      the HIPP and mPFC or the MS and mPFC simultaneously, and these double-projecting
      cells are also predominantly vGluT3-positive. Our results indicate that the
      majority of the output of the MRR is glutamatergic and acts through NMDA receptor
      containing synapses. This suggests that key forebrain areas receive precisely
      targeted excitatory input from the MRR, which is able to synchronously modify
      activity in those regions via individual MRR cells with dual projections. 

PMID- 25381464
TI  - Morphology and dendritic maturation of developing principal neurons in the rat
      basolateral amygdala.
AB  - The basolateral nucleus of the amygdala (BLA) assigns emotional valence to
      sensory stimuli, and many amygdala-dependent behaviors undergo marked development
      during postnatal life. We recently showed principal neurons in the rat BLA
      undergo dramatic changes to their electrophysiological properties during the
      first postnatal month, but no study to date has thoroughly characterized changes
      to morphology or gene expression that may underlie the functional development of
      this neuronal population. We addressed this knowledge gap with reconstructions of
      biocytin-filled principal neurons in the rat BLA at postnatal days 7 (P7), 14,
      21, 28, and 60. BLA principal neurons underwent a number of morphological
      changes, including a twofold increase in soma volume from P7 to P21. Dendritic
      arbors expanded significantly during the first postnatal month and achieved a
      mature distribution around P28, in terms of total dendritic length and distance
      from soma. The number of primary dendrites and branch points were consistent with
      age, but branch points were found farther from the soma in older animals.
      Dendrites of BLA principal neurons at P7 had few spines, and spine density
      increased nearly fivefold by P21. Given the concurrent increase in dendritic
      material, P60 neurons had approximately 17 times as many total spines as P7
      neurons. Together, these developmental transitions in BLA principal neuron
      morphology help explain a number of concomitant electrophysiological changes
      during a critical period in amygdala development. 

PMID- 25381465
TI  - Revisiting heritability accounting for shared environmental effects and maternal
      inheritance.
AB  - Heritability measures the proportion of phenotypic variation attributable to
      genetic factors. In addition to a shared nuclear genetic component, a number of
      additional variance components, such as spousal correlation, sibship, household
      and maternal effects, may have strong contributions to inter-individual phenotype
      variation. In humans, the confounding effects of these components on heritability
      have not been studied thoroughly. We sought to obtain unbiased heritability
      estimates for complex traits in the presence of multiple variance components and
      also to estimate the contributions of these variance components to complex
      traits. We compared regression and variance component methods to estimate
      heritability in simulations when additional variance components existed. We then
      revisited heritability for several traits in Framingham Heart Study (FHS)
      participants. Using simulations, we found that failure to account for or
      misclassification of necessary variance components yielded biased heritability
      estimates. The direction and magnitude of the bias varied depending on a variance
      structure and an estimation method. Using the best fitted models to account for
      necessary variance components, we found that heritability estimates for most FHS
      traits were overestimated, ranging from 4 to 47 %, when we compared models that
      considered necessary variance components to models that only considered familial
      relationships. Spousal correlation explained 14-36 % of phenotypic variation in
      several anthropometric and lifestyle traits. Maternal and sibling effects also
      contributed to phenotypic variation, ranging from 3 to 5 % and 4 to 7 %,
      respectively, in several anthropometric and metabolic traits. Our findings may
      explain, in part, the missing heritability for some traits. 

PMID- 25381467
TI  - Isolated patellofemoral arthroplasty reproduces natural patellofemoral joint
      kinematics when the patella is resurfaced.
AB  - PURPOSE: The objectives of this in vitro project were to compare the dynamic
      three-dimensional patellofemoral kinematics, contact forces, contact areas and
      contact pressures of a contemporary patellofemoral prosthetic implant with those
      of the native knee and to measure the influence of patellar resurfacing and
      patellar thickness. The hypothesis was that these designs are capable to
      reproduce the natural kinematics but result in higher contact pressures. METHODS:
      Six fresh-frozen specimens were tested on a custom-made mechanical knee rig
      before and after prosthetic trochlear resurfacing, without and with patellar
      resurfacing in three different patellar thicknesses. Full three-dimensional
      kinematics were analysed during three different motor tasks, using infrared
      motion capture cameras and retroflective markers. Patellar contact
      characteristics were registered using a pressure measuring device. RESULTS: The
      patellofemoral kinematic behaviour of the patellofemoral arthroplasty was similar
      to that of the normal knee when the patella was resurfaced, showing only
      significant (p < 0.0001) changes in patellar flexion. Without patellar
      resurfacing, significant more patellar flexion, lateral tilt and lateral rotation
      was noticed. Compared to the normal knee, contact pressures were significantly
      elevated after isolated trochlear resurfacing. However, the values were more than
      doubled after patellar resurfacing. Changes in patellar thickness only influenced
      the antero-posterior patellar position. There was no other influence on the
      kinematics, and only a limited influence on the contact pressures in the low
      flexion angles. CONCLUSION: The investigated design reproduced the normal
      patellofemoral kinematics acceptable well when the patella was resurfaced. From a
      kinematic point of view, patellar resurfacing may be advisable. However, the
      substantially elevated patellar contact pressures remain a point of concern in
      the decision whether or not to resurface the patella. This study therefore not
      only adds a new point in the discussion whether or not to resurface the patella,
      but also supports the claimed advantage that a patellofemoral arthroplasty is
      capable to reproduce the natural knee kinematics.

PMID- 25381466
TI  - Rare germline copy number deletions of likely functional importance are
      implicated in endometrial cancer predisposition.
AB  - Endometrial cancer is the most common invasive gynaecological cancer in women,
      and relatively little is known about inherited risk factors for this disease.
      This is the first genome-wide study to explore the role of common and rare
      germline copy number variants (CNVs) in predisposition to endometrial cancer.
      CNVs were called from germline DNA of 1,209 endometrioid endometrial cancer cases
      and 528 cancer-unaffected female controls. Overall CNV load of deletions or DNA
      gains did not differ significantly between cases and controls (P > 0.05), but
      cases presented with an excess of rare germline deletions overlapping likely
      functional genomic regions including genes (P = 8 * 10(-10)), CpG islands (P = 1
      * 10(-7)) and sno/miRNAs regions (P = 3 * 10(-9)). On average, at least one
      additional gene and two additional CpG islands were disrupted by rare deletions
      in cases compared to controls. The most pronounced difference was that over 30
      sno/miRNAs were disrupted by rare deletions in cases for every single disruption
      event in controls. A total of 13 DNA repair genes were disrupted by rare
      deletions in 19/1,209 cases (1.6%) compared to one gene in 1/528 controls (0.2%;
      P = 0.007), and this increased DNA repair gene loss in cases persisted after
      excluding five individuals carrying CNVs disrupting mismatch repair genes MLH1,
      MSH2 and MSH6 (P = 0.03). There were 34 miRNA regions deleted in at least one
      case but not in controls, the most frequent of which encompassed hsa-mir-661 and
      hsa-mir-203. Our study implicates rare germline deletions of functional and
      regulatory regions as possible mechanisms conferring endometrial cancer risk, and
      has identified specific regulatory elements as candidates for further
      investigation.

PMID- 25381468
TI  - All-inside suture device is superior to meniscal arrows in meniscal repair: a
      prospective randomized multicenter clinical trial with 2-year follow-up.
AB  - PURPOSE: Multiple techniques and implants are available for all-inside meniscal
      repair, but the knowledge about their failure rates and functional outcome is
      still incomplete. The hypothesis was that there might be differences between
      meniscal arrows and suture devices regarding reoperation rates and functional
      outcome. Thereby, the aim of this study was to compare clinical results following
      repair with the Biofix((r)) arrows or the FasT-Fix((r)) suture devices. METHODS:
      In this RCT, 46 patients were treated either by Biofix((r)) (n = 21) or FasT
      Fix((r)) (n = 25). The main outcome was reoperation within 2 years. Knee function
      and activity level were evaluated by KOOS and Tegner activity scale. RESULTS:
      Twelve out of 46 (26%) patients were reoperated within 2 years, nine out of 21
      (43%) in the Biofix((r))-group versus three out of 25 (12%) in the FasT-Fix((r))
      group (p = 0.018). The relative risk of reoperation was 3.6 times higher for
      Biofix((r)) compared to FasT-Fix((r)) (95% confidence interval 1.1-11.5). Both
      treatment groups had significant increase in all KOOS subscales, but there were
      no major differences between the groups. The subgroup of reoperated patients
      differed from the other patients with higher Tegner score preoperatively (median
      5 vs. 4) (p = 0.037) and at 3-month follow-up (median 4 vs. 3) (p = 0.010).
      CONCLUSIONS: These results indicate that FasT-Fix((r)) suture is superior to
      Biofix((r)) arrows with significant lower failure rate. Functional outcome did
      not depend on repair technique. Higher activity score preoperatively and at 3
      month follow-up in the reoperated patients indicates that activity level may
      influence on the risk of reoperation. LEVEL OF EVIDENCE: I.

PMID- 25381469
TI  - A rare case of insulinoma presenting with postprandial hypoglycemia.
AB  - BACKGROUND: Although fasting hypoglycemia has historically been considered the
      hallmark of insulinoma, postprandial hypoglycemia has also been occasionally
      reported as the predominant feature. We report a rare case of an insulinoma
      diagnosed in an individual presenting exclusively with postprandial hypoglycemia
      without fasting hypoglycemia. CASE REPORT: A 47-year-old woman with medical
      history of migraine, depression, hypercholesterolemia, iron deficiency anemia,
      and peptic ulcer disease presented with complaints of frequent episodes of
      dizziness, blurring of vision, and anxiety over the past 4 months. These episodes
      usually occurred 1-2 hours after eating and resolved with ingestion of sugary
      foods. Home glucometer readings during typical symptoms were 47-64 mg/dL.
      Physical exam revealed a healthy-appearing middle-aged female with BMI of 28.
      Laboratory data after an overnight fast showed serum blood glucose 77 mg/dL and
      AM cortisol 9.6 (5-25 ug/dl). Hemoglobin A1C, thyroid function tests, IGF-1,
      liver function tests, and kidney function were in normal range. She was
      instructed to bring a typical meal to the clinic for monitoring of postprandial
      glucose levels. Three hours after ingestion of the meal, she developed typical
      adrenergic symptoms during which laboratory analysis revealed a serum glucose
      level of 44 mg/dL, C-peptide of 2.9 (0.8-3.1 ng/ml), insulin level of 32 (0-17
      uIU/lt), negative sulfonylurea screen, and insulin antibodies. She was treated
      with 15 grams of oral glucose, which alleviated her symptoms. Medical therapy
      with acarbose was attempted, but did not lead to significant reduction in
      hypoglycemic events. CT abdomen/pelvis confirmed the presence of a tumor in the
      tail of the pancreas. The patient subsequently underwent partial pancreatectomy,
      splenectomy, and lymph node resection, with resolution of symptoms.
      Histopathological analysis confirmed insulinoma. CONCLUSIONS: We present a rare
      case of an insulinoma in the setting of verified postprandial hypoglycemia with
      elevated insulin and C-peptide levels. Although insulinomas typically present
      with fasting hypoglycemia, it is important to consider insulinoma in the
      differential diagnosis of patients presenting exclusively with postprandial
      hypoglycemia.

PMID- 25381470
TI  - Clinical outcomes of trochanteric syndrome endoscopically treated.
AB  - BACKGROUND: Greater trochanteric pain syndrome (GTPS) is clinically defined as
      greater trochanter pain with mechanical characteristics. Most cases of GTPS are
      resolved with conservative treatment. Surgical techniques are reserved for those
      who had unsatisfactory results with conservative treatment. PURPOSE: The aim of
      the present paper is to describe the outcomes observed within endoscopic
      treatment of peritrochanteric pathology. METHODS: Twenty-three patients were
      included in the present study, undergoing surgery between January 2010 and
      December 2011, diagnosed with GTPS and surgically treated with endoscopy. All
      patients were evaluated with Visual Analogue Scale (VAS), Western Ontario and
      McMaster Universities Arthritis Index (WOMAC) Modified Harris Hip Score (mHHS)
      and Hip Outcome Score (HOS). The Scales were assessed before surgery and at 3, 6
      and 12 months postoperatively. RESULTS: All scores showed statistically
      significant differences (p < 0.001) within all periods. CONCLUSION: The
      endoscopic technique has proven to be safe and reproducible with good and
      excellent results, thus being an additional surgical procedure to consider within
      therapeutic management of greater trochanteric pain syndrome. LEVEL OF EVIDENCE:
      IV. Case series.

PMID- 25381471
TI  - A comparison of acute and chronic anterior cruciate ligament reconstruction using
      LARS artificial ligaments: a randomized prospective study with a 5-year follow
      up.
AB  - PURPOSE: This prospective randomized study compared acute and chronic anterior
      cruciate ligament (ACL) reconstruction using ligament advanced reinforcement
      system (LARS) artificial ligament in young active adults with a 5-year follow-up.
      METHODS: Fifty-five patients were enrolled in this study and divided into two
      groups based on the elapsed time between the injury and reconstruction: the acute
      group (3-7 weeks) and the chronic group (6-11 months). The clinical outcomes were
      evaluated using the Lysholm knee scoring scale, the Tegner activity rating, a KT
      1000 Arthrometer, and the International Knee Documentation Committee (IKDC)
      scoring system. Isokinetic strength of the quadriceps and hamstring was assessed
      using the Biodex System 3 isokinetic dynamometer. RESULTS: Anterior laxity was
      decreased and quadriceps/hamstring muscle strength was increased in the acute
      group compared to the chronic group (p > 0.05). There were no statistically
      significant differences in Lysholm scores, Tegner activity scores, and the IKDC
      evaluation form between the two groups. CONCLUSIONS: These results suggest that
      earlier ACL reconstruction using a LARS artificial ligament may provide an
      advantage in the treatment and rehabilitation of ACL rupture.

PMID- 25381472
TI  - Corticosteroid injection for trigger finger: blinded or ultrasound-guided
      injection?
AB  - INTRODUCTION: Trigger digit is one of the most common causes of pain and
      disability in the hand. The mainstay of conservative treatment of this disease
      has been local steroid injection into the tendon sheath. The aim of this study
      was to investigate the clinical benefit of an ultrasound-guided corticosteroid
      injection compared to a blinded application. MATERIALS AND METHODS: 74 patients,
      who suffered from persistent or increasing symptoms of a single trigger digit,
      were enroled in this prospective, randomised case-control study. All patients
      were treated with an injection of 40 mg/1 ml methylprednisolone acetate into the
      flexor tendon sheath at the level of the A1 pulley. Half of the patients had
      their injections under ultrasound control (USG) and half without (blinded
      injection group, BIG). Associated metabolic diseases were recorded. At the 6-week
      and 6-month follow-up examinations, the complication rate and the need for a
      second injection were assessed. The outcome was rated using the Quinnell grading.
      The pain level was assessed using the visual analogue scale. RESULTS: Four
      patients were excluded due to lack of follow-up. Both study groups were
      comparable in respect of age, hand dominance and associated diseases. There were
      significantly more female patients in the USG group (32 versus 23 %). After the
      corticosteroid injections, all patients improved significantly in terms of pain
      level and the Quinnell grading at 6 weeks and 6 months after the intervention in
      comparison to the pre-injection status. There were no significant differences
      between the groups. 9 patients (13 %) needed a second injection (6 of BIG, 3 of
      USG), all of whom had diabetes mellitus. No local complications were seen after
      the injections. CONCLUSION: The use of ultrasound-guided injection of
      corticosteroid may be associated with extra time and effort, with no superior
      clinical benefits compared to the blinded technique. LEVEL OF EVIDENCE: Level
      1(prospective randomised study).

PMID- 25381473
TI  - The roles of Egr-2 in autoimmune diseases.
AB  - Being a member of the early growth response (Egr) family of transcription
      factors, Egr-2 is expressed in a variety of cell types of the immune system.
      Recent findings imply that Egr-2 is important in the development and function of
      T helper (Th) 17 cell, regulatory T (Treg) cell, as well as dendritic cell (DC).
      Although these cells perform significantly in the pathogenesis of autoimmune
      diseases, such as systemic lupus erythematosus, multiple sclerosis, and systemic
      sclerosis, the roles of Egr-2 in the pathogenesis of autoimmune diseases can not
      be neglected. In this article, we will discuss recent findings about the
      important roles of Egr-2 in immune cells and the possible pathological roles of
      Egr-2 in autoimmune diseases. 

PMID- 25381474
TI  - Role of neurotrophin in the taste system following gustatory nerve injury.
AB  - Taste system is a perfect system to study degeneration and regeneration after
      nerve injury because the taste system is highly plastic and the regeneration is
      robust. Besides, degeneration and regeneration can be easily measured since taste
      buds arise in discrete locations, and nerves that innervate them can be
      accurately quantified. Neurotrophins are a family of proteins that regulate
      neural survival, function, and plasticity after nerve injury. Recent studies have
      shown that neurotrophins play an important role in the developmental and mature
      taste system, indicating neurtrophin might also regulate taste system following
      gustatory nerve injury. This review will summarize how taste system degenerates
      and regenerates after gustatory nerve cut and conclude potential roles of
      neurotrophin in regulating the process.

PMID- 25381475
TI  - Wogonin prevents rat dorsal root ganglion neurons death via inhibiting
      tunicamycin-induced ER stress in vitro.
AB  - Wogonin is a natural flavonoid isolated from the root of Scutellaria baicalensis
      Georgi, which has been widely used in various research areas for its anti
      oxidant, anti-inflammatory, and anti-cancer activities. It also presents a
      neuroprotective effect in the brain while encounters stress conditions, but the
      mechanisms controlling the neuroprotective effect of wogonin are not clear. In
      this study, we investigated the biomechanism underlying the neuroprotective
      effect of wogonin on rat dorsal root ganglion (DRG) neurons. Wogonin pre
      treatment at 75 MUM significantly increased the cell viability of DRG neurons and
      decreased the number of the propidium iodide-positive DRG neurons before the
      endoplasmic reticulum (ER) stress is being induced by tunicamycin (TUN) (0.75
      MUg/mL). In addition, Wogonin also inhibited the release of LDH and up-regulated
      the level of GSH. Furthermore, wogonin decreased the activation of ER stress
      related molecules, including glucose-regulated protein 78 (GRP78), GRP94, C/EBP
      homologous protein, active caspase12 and active caspase3, phosphorylation of
      pancreatic ER stress kinase, and eukaryotic initiation factor 2 alpha
      (eIF2alpha). In summary, our results indicated that wogonin could protect DRG
      neurons against TUN-induced ER stress. 

PMID- 25381476
TI  - Prophylactic procedure for inguinal hernia after radical retropubic
      prostatectomy.
AB  - PURPOSE: The incidence of inguinal hernias (IH) after radical retropubic
      prostatectomy (RRP) has been reported to range from 10 to 50 %, but no
      prophylaxis for IH has yet been established. We proposed a prophylaxis for IH
      after RRP. METHODS: A total of 180 patients underwent RRP at our hospital between
      2000 and 2011. In January 2008, we started to perform a prophylaxis involving the
      dissection of the processus vaginalis. This procedure was performed in 73
      patients. We then compared the incidence of IH between the patients that did
      (prophylaxis group) and did not (no prophylaxis group) undergo the prophylaxis.
      We also studied the risk factors for IH after RRP. RESULTS: In the no prophylaxis
      group, 25 (23 %) of the 107 patients developed IH, and the IH-free rate at one
      postoperative year was 86 %. In contrast, only 3 (4.1 %) of the 73 patients in
      the prophylaxis group developed IH, resulting in IH-free rate of 96 % at one
      postoperative year (P = 0.0235). Among the patients in the no prophylaxis group,
      the mean body mass index of the hernia group was significantly lower than that of
      the no hernia group (P = 0.006). CONCLUSION: Our results suggest that our
      prophylaxis is useful for preventing IH after RRP.

PMID- 25381477
TI  - Influence of dual antiplatelet therapy on mean platelet volume in patients with
      coronary artery disease undergoing percutaneous coronary intervention.
AB  - Mean platelet volume (MPV) is a well-established marker of platelet activation,
      and recent studies have shown that platelet activation is central to the
      processes in the pathophysiology of coronary artery disease (CAD). The study
      population consisted of 45 patients with stable CAD who underwent successful
      percutaneous coronary intervention (PCI) with drug-eluting stents. We selected 45
      age- and sex-matched control subjects without cardiovascular diseases who did not
      require antiplatelet therapy. Hematological test was performed 3 times within 1
      month before DAPT (baseline), at 2 weeks after PCI (post PCI) and at 9 months
      after PCI (follow-up). Compared to control subjects, MPV was significantly larger
      in patients with CAD (10.0 +/- 0.6 vs 10.7 +/- 0.8 fl, p < 0.01) although there
      was no significant difference in white blood cell count, hemoglobin, and platelet
      count between the 2 groups. In patients with CAD, DAPT did not affect platelet
      count (19.3 +/- 4.8 * 10(4)-18.9 +/- 4.6 * 10(4)/MUl) or MPV (10.7 +/- 0.8-10.5
      +/- 0.9 fl) during the follow-up period. MPV remained to be higher at follow-up
      in patients with CAD despite DAPT compared to control subjects (10.1 +/- 0.7 vs
      10.5 +/- 0.9 fl, p < 0.05). Our data suggested that MPV might not be suitable for
      monitoring the effects of DAPT on platelet activity in patients with CAD
      undergoing PCI.

PMID- 25381478
TI  - Five-year results of laparoscopic sleeve gastrectomy in Korean patients with
      lower body mass index (30-35 kg/m2).
AB  - BACKGROUND: In Asia, laparoscopic sleeve gastrectomy (LSG) is the leading weight
      loss procedure for treating morbid obesity. However, long-term results of
      isolated LSG performed in patients with lower body mass index (BMI) (30-35
      kg/m(2)) are scarce. METHODS: We retrospectively reviewed 75 patients with BMI of
      30-35 kg/m(2) who underwent LSG from January 2003 to January 2013. Seventy-one of
      these patients who had more than 6 months of follow-up were included in this
      report. LSG was performed laparoscopically using a linear stapler over a 48
      French bougie from 2003 to 2006. Since 2007, 36-French bougie was used for
      resection, and a continuous seromuscular suture at the resection margin was
      added. RESULTS: Mean age at the time of surgery was 33.7 +/- 10.3 years in our
      patients. Mean weight was 85.7 +/- 9.0 kg and mean BMI was 32.4 +/- 1.6 kg/m(2)
      preoperatively. The percentage of excess BMI loss (%EBL) in the postoperative
      first, third, and fifth year was 84.1 +/- 25.5, 79.8 +/- 31.0, and 78.5 +/-
      28.5%, respectively. Follow-up rate at the first, third, and fifth year was 90.0,
      71.9, and 42.9%. There were no 30-day perioperative mortality and major
      complications including bleeding and leakage. CONCLUSIONS: These findings show
      that LSG is a safe and effective weight loss option for Korean patients with
      lower BMI. Randomized prospective control studies between gastric banding, or
      Roux-en-Y gastric bypass, and LSG are needed to confirm long-term weight loss
      effect and safety of LSG in this group of patients.

PMID- 25381479
TI  - Potential roles of self-reactive T cells in autoimmunity: lessons from cancer
      immunology.
AB  - The immune system is a complex arrangement of cells and molecules that preserve
      the integrity of the organism by eliminating all elements judged to be dangerous.
      Several regulatory mechanisms function to terminate immune responses to antigens,
      return the immune system to a basal state after the antigen has been cleared, and
      maintain unresponsiveness, or tolerance, to self-antigens. In recent years,
      reports have described T cell responses to several proteins involved in
      regulating the immune system, particularly under malignant conditions. The
      present review highlights specific T cells that recognize proteins involved in
      three, well-defined immunosuppressive mechanisms: (1) inhibitory T cell pathways
      (i.e., PD-L1), (2) regulatory T cells (i.e., Foxp3(+)), and (3) metabolic
      enzymes, like indoleamine-2,3-dioxygenase. Cytotoxic T cells can eliminate
      regulatory cells, thereby suppressing and/or delaying local immune suppression;
      conversely, regulatory CD4(+) and non-cytotoxic CD8(+) T cells enhance target
      mediated immune suppression. The apparent lack of tolerance against endogenous
      proteins expressed by regulatory cells is intriguing, because it suggests that
      self-reactive T cells play a general role of fine-tuning the immune system. Thus,
      T cell responses may be generally used to maintain the homeostasis of the immune
      system. Further exploration is warranted to investigate the potential role of
      auto-reactive T cells under different physiological and/or pathological
      conditions. 

PMID- 25381480
TI  - Silenced suppressor of cytokine signaling 1 (SOCS1) enhances the maturation and
      antifungal immunity of dendritic cells in response to Candida albicans in vitro.
AB  - Dendritic cells (DCs) are known to play an important role in initiating and
      orchestrating antimicrobial immunity. Given the fact that candidiasis appears
      often in immunocompromised patients, it seems plausible that DCs hold the key to
      new antifungal strategies. One possibility to enhance the potency of DC-based
      immunotherapy is to silence the negative immunoregulatory pathways through the
      ablation suppressor of cytokine signaling suppressor 1 (SOCS1). Here, we deliver
      small interfering RNA (siRNA) against SOCS1 into murine bone marrow DCs, and as a
      consequence, we investigate the maturation/action of DCs and the subsequent T
      cell response after exposure to C. albicans. Our results show that the maturation
      of DCs (i.e., expressions of CD80, CD40, CD86, and MHC II) are significantly
      increased in the silenced SOCS1 treatment group after exposure to C. albicans. As
      a result, suppression of the SOCS1 promotes the greatest expression of IFN-gamma
      and IL-12, and reduces IL-4 secretions, which induce CD4(+) cell Th1
      differentiation but inactivate Th2 cell development. The responses of IL-6 and
      TNF-beta consist of up-regulation in the presence of C. albicans, but this is not
      specific to SOCS1 silencing, suggesting that these cytokines are not regulated by
      the SOCS1 gene in fungal infections. We find Th17 differentiation is unchanged
      regardless of SOCS1 inhibition. The increase in phagocytosis and killing of C.
      albicans in SOCS1 gene-treated DCs indicate a role for this cytokine suppressor
      in innate immunity as well. In conclusion, our findings support the view that
      SOCS1 protein is a critical inhibitory molecule for controlling cytokine response
      and antigen presentation by DCs, thereby regulating the magnitude of innate and
      adaptive immunities by generating IFN-gamma-production T cells (Th1)--but not
      Th17--from naive CD4(+) T cells. Our study demonstrates that SOCS1 siRNA can
      serve as a useful vehicle to modulate the function of DCs against C. albicans
      infection.

PMID- 25381481
TI  - New treatments for inflammatory rheumatic disease.
AB  - As our understanding of the pathogenesis of autoimmune diseases is growing, new
      therapies are being developed to target disease-specific pathways. Since the
      introduction of etanercept in 1998, several biotechnological agents have been
      developed, most of them indicated in the treatment of rheumatoid arthritis, but
      also psoriatic arthritis. Most currently available molecules target TNF-alfa with
      different strategies (i.e., etanercept, infliximab, adalimumab, golimumab, and
      certolizumab pegol), IL-6 (tocilizumab), CTLA-4 (abatacept), and B cells
      (rituximab, belimumab) as they are key mediators in the cascade of inflammation.
      Further, small molecules have been recently developed to target intracellular
      signaling, such as Janus Kinases for tofacitinib, the first FDA-approved small
      molecule for rheumatoid arthritis. Most novel treatments are being developed for
      arthritis with specific differences between rheumatoid and psoriatic arthritis,
      as well as for systemic lupus erythematosus, following the approval of belimumab.
      Finally, biologic therapies are effective also in gout, mainly targeting
      interleukin-1 to block the inflammasome. This review article describes the new
      and upcoming treatment options for rheumatoid arthritis, psoriatic arthritis,
      systemic lupus erythematosus, and gout to dissect what we should be aware of when
      discussing these new and promising molecules.

PMID- 25381482
TI  - The epidemiological profile of ASIA syndrome after HPV vaccination: an evaluation
      based on the Vaccine Adverse Event Reporting Systems.
AB  - The term "ASIA-Autoimmune/inflammatory Syndrome Induced by Adjuvants" describes
      an umbrella of clinical conditions sharing similar signs or symptoms, including
      post-vaccination phenomena. No information is available on the epidemiology of
      the ASIA syndrome, especially following HPV vaccination. We carried out an
      analysis of the VAERS database to retrieve all cases of suspected ASIA syndrome
      according to the Shoenfeld and Agmon-Levin's guideline for the diagnosis. After
      causality assessment and case validation, 2,207 cases were considered probably or
      possibly related to vaccination. These represent the largest ASIA cohort ever
      reported and allowed us to estimate epidemiological and clinical characteristic
      of this syndrome. The commonest clinical manifestation observed were pyrexia
      (58%), myalgia (27%) and arthralgia or arthritis (19%), and the estimated
      reporting rate was of 3.6 cases per 100,000 doses of HPV vaccine distributed (95%
      CI 3.4-3.7). This study presents the first systematic estimation of ASIA
      incidence and expands the knowledge on this pathology. Further analyses are
      needed to identify genetic and non-genetic risk factors for ASIA syndrome.

PMID- 25381484
TI  - Cardiac blood pool activity on postablation radioiodine imaging.
AB  - OBJECTIVE: There are reports on physiologic and pathologic mediastinal uptake on
      radioiodine imaging in patients with thyroid carcinoma. The most commonly
      reported physiologic causes of mediastinal uptake are esophageal retention of
      salivary secretion and uptake by hyperplastic or normal thymus gland. In this
      study, we evaluated physiologic cardiac blood pool (CBP) activity and its
      associated findings on radioiodine imaging. METHODS: Cardiac blood pool activity
      was evaluated in 186 postablation and 32 posttherapy scans. After oral
      radioiodine administration, imaging was initiated on day 7. Thyroglobulin, anti
      thyroglobulin and TSH blood level determination was carried out in all patients.
      Whole-body scans were inspected with regard to residual thyroid uptake,
      esophageal uptake, CBP activity, hepatic activity and metastatic iodine uptake.
      Uptake in the residual thyroid tissue was graded visually as mild (m), moderate
      (M) and significant (S). Whenever CBP activity was detected on visual inspection,
      its intensity was graded as mild (1), moderate (2), and significant (3). RESULTS:
      Cardiac blood pool activity was detected in 61 postablation scans (33 %).
      Residual thyroid uptake was observed in all patients with CBP. A significant
      correlation existed between the intensity of uptake and the presence of CBP (p <
      0.05). The mean Tg in patients with CBP was significantly higher than those
      without CBP (p < 0.05). Cardiac blood pool activity was not observed in any
      posttherapy scans and in those scans with distant metastases in the postablation
      group. Linear or irregular activity pattern thought to be due to esophagus was
      detected in 4 % of postablation scans. CONCLUSIONS: The results have revealed CBP
      to be common on postablation scans. Its presence correlated with the intensity of
      residual thyroid uptake and had a significant association with increased
      thyroglobulin levels. Its absence on posttherapy scans despite increased Tg
      levels suggested that this activity is due to labeled thyroid hormones released
      by the residual thyroid tissue. Its presence might imply a high level of blood
      radiation dose.

PMID- 25381485
TI  - Epilepsy but not mobile phone frequency (900 MHz) induces apoptosis and calcium
      entry in hippocampus of epileptic rat: involvement of TRPV1 channels.
AB  - Electromagnetic radiation (EMR) and epilepsy are reported to mediate the
      regulation of apoptosis and oxidative stress through Ca(2+) influx. Results of
      recent reports indicated that EMR can increase temperature and oxidative stress
      of body cells, and TRPV1 channel is activated by noxious heat, oxidative stress,
      and capsaicin (CAP). We investigated the effects of mobile phone (900 MHz) EMR
      exposure on Ca(2+) influx, apoptosis, oxidative stress, and TRPV1 channel
      activations in the hippocampus of pentylenetetrazol (PTZ)-induced epileptic rats.
      Freshly isolated hippocampal neurons of twenty-one rats were used in study within
      three groups namely control, PTZ, and PTZ + EMR. The neurons in the three groups
      were stimulated by CAP. Epilepsy was induced by PTZ administration. The neurons
      in PTZ + EMR group were exposed to the 900 MHz EMR for 1 h. The apoptosis,
      mitochondrial membrane depolarization, intracellular reactive oxygen species
      (ROS), and caspase-3 and caspase-9 values were higher in PTZ and PTZ + EMR groups
      than in control. However, EMR did not add additional increase effects on the
      values in the hippocampal neurons. Intracellular-free Ca(2+) concentrations in
      fura-2 analyses were also higher in PTZ + CAP group than in control although
      their concentrations were decreased by TRPV1 channel blocker, capsazepine.
      However, there were no statistical changes on the Ca(2+) concentrations between
      epilepsy and EMR groups. In conclusion, apoptosis, mitochondrial, ROS, and Ca(2+)
      influx via TRPV1 channel were increased in the hippocampal neurons by epilepsy
      induction although the mobile phone did not change the values. The results
      indicated that TRPV1 channels in hippocampus may possibly be a novel target for
      effective target of epilepsy.

PMID- 25381483
TI  - Cytokines and HCV-related autoimmune disorders.
AB  - Cytokines are intercellular mediators involved in viral control and liver damage
      being induced by infection with hepatitis C virus (HCV). The complex cytokine
      network operating during initial infection allows a coordinated, effective
      development of both innate and adaptive immune responses. However, HCV interferes
      with cytokines at various levels and escapes immune response by inducing a T
      helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads
      to the recruitment of inflammatory infiltrates into the liver parenchyma by
      interferon (IFN)-gamma-inducible CXC chemokine ligand (CXCL)9, -10, and -11
      chemokines, which results in sustained liver damage and eventually in liver
      cirrhosis. The most important systemic HCV-related extrahepatic diseases-mixed
      cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders,
      and type 2 diabetes-are associated with a complex dysregulation of the
      cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The
      therapeutical administration of cytokines such as IFN-alpha may result in viral
      clearance during persistent infection and revert this process. Theoretically
      agents that selectively neutralize CXCL10 could increase patient responsiveness
      to traditional IFN-based HCV therapy. Several studies have reported IL-28B
      polymorphisms and circulating CXCL10 may be a prognostic markers for HCV
      treatment efficacy in HCV genotype 1 infection. 

PMID- 25381486
TI  - Comparison of the efficacy of chlorhexidine gluconate versus povidone iodine as
      preoperative skin preparation for the prevention of surgical site infections in
      clean-contaminated upper abdominal surgeries.
AB  - PURPOSE: To compare the efficacy of chlorhexidine-gluconate versus povidone
      iodine in preoperative skin preparation in the prevention of surgical site
      infections (SSIs) in clean-contaminated upper abdominal surgeries. METHODS: This
      was a prospective randomized controlled trial conducted on patients undergoing
      clean-contaminated upper abdominal surgeries. A total of 351 patients 18-70 years
      old were randomized into two groups; chlorhexidine and povidone iodine skin
      preparation before surgery. RESULTS: The incidence of SSIs in the chlorhexidine
      group was 10.8 %, in comparison to 17.9 % in the povidone iodine group. The odds
      ratio was 0.6 in favor of chlorhexidine use, but the results were not
      statistically significant (P = 0.06). In the first postoperative week, SSIs
      developed in 7 % of patients in the chlorhexidine group and 14.1 % in the
      povidone iodine group (P = 0.03), and in the second postoperative week, SSIs were
      present in 4.1 % of the patients in the chlorhexidine group and 4.4 % in the
      povidone iodine group, which was not statistically significant (P = 0.88).
      CONCLUSIONS: The incidence of SSIs after clean-contaminated upper abdominal
      surgeries was lower with the use of chlorhexidine skin preparation than with
      povidone iodine preparation, although the results were not statistically
      significant. However, the odds ratio between the two groups favored the use of
      chlorhexidine over povidone iodine for preventing SSIs.

PMID- 25381487
TI  - Efficacy of synthetic peptide candidate vaccines against serotype-A foot-and
      mouth disease virus in cattle.
AB  - Foot-and-mouth disease (FMD) remains a major threat to livestock worldwide,
      especially in developing countries. To improve the efficacy of vaccination
      against FMD, various types of vaccines have been developed, including synthetic
      peptide vaccines. We designed three synthetic peptide vaccines, 59 to 87 aa in
      size, based on immunogenic epitopes in the VP1, 3A, and 3D proteins of the
      A/HuBWH/CHA/2009 strain of the foot-and-mouth disease virus (FMDV), corresponding
      to amino acid positions 129 to 169 of VP1, 21 to 35 of 3A, and 346 to 370 of 3D.
      The efficacies of the vaccines were evaluated in cattle and guinea pigs
      challenged with serotype-A FMDV. All of the vaccines elicited the production of
      virus-neutralizing antibodies. The PB peptide, which contained sequences
      corresponding to positions 129 to 169 of V P1 and 346 to 370 of 3D, demonstrated
      the highest levels of immunogenicity and immunoprotection against FMDV. Two doses
      of 50 MUg of the synthetic PB peptide vaccine provided 100% protection against
      FMDV infection in guinea pigs, and a single dose of 100 MUg provided 60%
      protection in cattle. These findings provide empirical data for facilitating the
      development of synthetic peptide vaccines against FMD.

PMID- 25381488
TI  - Manipulation of pyrite colonization and leaching by iron-oxidizing
      Acidithiobacillus species.
AB  - In this study, the process of pyrite colonization and leaching by three iron
      oxidizing Acidithiobacillus species was investigated by fluorescence microscopy,
      bacterial attachment, and leaching assays. Within the first 4-5 days, only the
      biofilm subpopulation was responsible for pyrite dissolution. Pyrite-grown cells,
      in contrast to iron-grown cells, were able to oxidize iron(II) ions or pyrite
      after 24 h iron starvation and incubation with 1 mM H2O2, indicating that these
      cells were adapted to the presence of enhanced levels of reactive oxygen species
      (ROS), which are generated on metal sulfide surfaces. Acidithiobacillus
      ferrivorans SS3 and Acidithiobacillus ferrooxidans R1 showed enhanced pyrite
      colonization and biofilm formation compared to A. ferrooxidans (T). A broad range
      of factors influencing the biofilm formation on pyrite were also identified, some
      of them were strain-specific. Cultivation at non-optimum growth temperatures or
      increased ionic strength led to a decreased colonization of pyrite. The presence
      of iron(III) ions increased pyrite colonization, especially when pyrite-grown
      cells were used, while the addition of 20 mM copper(II) ions resulted in reduced
      biofilm formation on pyrite. This observation correlated with a different
      extracellular polymeric substance (EPS) composition of copper-exposed cells.
      Interestingly, the addition of 1 mM sodium glucuronate in combination with
      iron(III) ions led to a 5-fold and 7-fold increased cell attachment after 1 and 8
      days of incubation, respectively, in A. ferrooxidans (T). In addition, sodium
      glucuronate addition enhanced pyrite dissolution by 25%.

PMID- 25381489
TI  - Two strictly polyphosphate-dependent gluco(manno)kinases from diazotrophic
      Cyanobacteria with potential to phosphorylate hexoses from polyphosphates.
AB  - The single-copy genes encoding putative polyphosphate-glucose phosphotransferases
      (PPGK, EC 2.7.1.63) from two nitrogen-fixing Cyanobacteria, Nostoc sp. PCC7120
      and Nostoc punctiforme PCC73102, were cloned and functionally characterized. In
      contrast to their actinobacterial counterparts, the cyanobacterial PPGKs have
      shown the ability to phosphorylate glucose using strictly inorganic
      polyphosphates (polyP) as phosphoryl donors. This has proven to be an
      economically attractive reagent in contrast to the more costly ATP.
      Cyanobacterial PPGKs had a higher affinity for medium-long-sized polyP (greater
      than ten phosphoryl residues). Thus, longer polyP resulted in higher catalytic
      efficiency. Also in contrast to most their homologs in Actinobacteria, both
      cyanobacterial PPGKs exhibited a modest but significant polyP-mannokinase
      activity as well. Specific activities were in the range of 180-230 and 2-3 MUmol
      min(-1) mg(-1) with glucose and mannose as substrates, respectively. No polyP
      fructokinase activity was detected. Cyanobacterial PPGKs required a divalent
      metal cofactor and exhibited alkaline pH optima (approx. 9.0) and a remarkable
      thermostability (optimum temperature, 45  degrees C). The preference for Mg(2+)
      was noted with an affinity constant of 1.3 mM. Both recombinant PPGKs are
      homodimers with a subunit molecular mass of ca. 27 kDa. Based on database
      searches and experimental data from Southern blots and activity assays, closely
      related PPGK homologs appear to be widespread among unicellular and filamentous
      mostly nitrogen-fixing Cyanobacteria. Overall, these findings indicate that polyP
      may be metabolized in these photosynthetic prokaryotes to yield glucose (or
      mannose) 6-phosphate. They also provide evidence for a novel group-specific
      subfamily of strictly polyP-dependent gluco(manno)kinases with ancestral features
      and high biotechnological potential, capable of efficiently using polyP as an
      alternative and cheap source of energy-rich phosphate instead of costly ATP.
      Finally, these results could shed new light on the evolutionary origin of sugar
      kinases.

PMID- 25381490
TI  - Characterization of maltotriose production by hydrolyzing of soluble starch with
      alpha-amylase from Microbulbifer thermotolerans DAU221.
AB  - A maltotriose-producing alpha-amylase, AmyA, from a newly isolated bacterial
      strain Microbulbifer thermotolerans DAU221 was purified and characterized in the
      heterologous host, Escherichia coli, using the pCold I vector. The amyA gene
      encoded a 761-residue protein composed of a 33 amino acid secretion signal
      peptide. The purified alpha-amylase with a molecular mass of 80 kDa,
      approximately, shared a sequence motif characteristic of the glycoside hydrolase
      family 13. The enzyme was optimally active, at 50  degrees C in sodium phosphate
      buffer (pH 6.0), by the traditional one factor-at-a-time method. But the optimal
      conditions of time, temperature, and pH for production of maltotriose from
      soluble starch were 1.76 h, 44.95  degrees C, and pH 6.35 by response surface
      methodology, respectively. Maltotriose, as the major enzyme reaction product, was
      analyzed by thin-layer chromatography (TLC) and high-performance liquid
      chromatography (HPLC). The enzyme was found to be inhibited by the addition of 10
      mM Cu(2+), Fe(3+), Hg(2+), Zn(2+), and EDTA, but exhibited extreme stability
      toward hexane. The K m and V max values for the hydrolysis of soluble starch were
      1.08 mg/mL and 1.736 mmol maltotriose/mg protein/min, respectively.

PMID- 25381491
TI  - Primary effects of extracellular enzyme activity and microbial community on
      carbon and nitrogen mineralization in estuarine and tidal wetlands.
AB  - Estuarine and tidal wetlands with high primary productivity and biological
      activity play a crucial role in coastal nutrient dynamics. Here, to better reveal
      the effects of extracellular enzymes and microbial community on carbon (C) and
      nitrogen (N) mineralization, the incubation experiments with different C and N
      addition patterns to the tidal sediments of the Yangtze Estuary (China) were
      conducted. The results suggested a significant increase in cumulative CO2
      effluxes in the C and CN treatment experiments, while no significant difference
      in cumulative CO2 effluxes between the N treatment and control (CK) experiments
      was observed. In addition, the nutrient addition patterns had a great influence
      on dissolve organic C and N levels, but a small effect on microbial biomass C and
      N. Microbial community composition and microbial activity were found to be
      positively correlated with organic C (OC) and the molar ratio of C to N (C/N).
      Partial correlation analysis, controlling for C/N, supported direct effects of OC
      on the activity of carbon-cycling extracellular enzymes (cellulase and polyphenol
      oxidase), while C/N exhibited negatively correlations with urease and Gram
      positive bacteria to Gram-negative bacteria (G+/G-). Strong relationships were
      found between CO2 efflux and mineral nitrogen with the activity of specific
      enzymes (sucrase, cellulase, and polyphenol oxidase) and abundances of Gram
      negative bacteria, arbuscular mycorrhizal fungi, and fungi, suggesting the
      significant influences of microbial community and enzyme activity on C and N
      mineralization in the estuarine and tidal wetlands. Furthermore, this study could
      highlight the need to explore effects of nutrient supply on microbial communities
      and enzyme activity changes associated with the C and N mineralization in these
      wetlands induced by the climate change. 

PMID- 25381492
TI  - Selective capture of transcribed sequences in the functional gene analysis of
      microbial pathogens.
AB  - Selective capture of transcribed sequences (SCOTS) is an effective method to
      identify bacterial genes differentially expressed during different biological
      processes, including pathogenic interactions with a host species. The method can
      be used to elucidate molecular mechanisms driving and maintaining such
      interactions. The method is a powerful genetic tool that overcomes limitations
      found in other methods, by working with small amounts of mRNA and allowing for
      the separation of bacterial cDNA from host cDNA. It has been increasingly used in
      the discovery of genes involved in the bacterium-host interaction. In this
      review, we briefly introduce the SCOTS method, outline the technical advances
      offered in the method, and focus on the method's applications in several
      microbial pathogens. 

PMID- 25381493
TI  - Communication: Non-Hadwiger terms in morphological thermodynamics of fluids.
AB  - We demonstrate that the Hadwiger form of the free energy of a fluid in contact
      with a wall is insufficient to describe the low-density behavior of a hard-sphere
      fluid. This implies that morphological thermodynamics of the hard-sphere fluid is
      an approximate theory if only four geometric measures are included. In order to
      quantify deviations from the Hadwiger form we extend standard fundamental measure
      theory of the bulk fluid by introducing additional scaled-particle variables
      which allow for the description of non-Hadwiger coefficients. The theory is in
      excellent agreement with recent computer simulations. The fact that the leading
      non-Hadwiger coefficient is one order of magnitude smaller than the smallest
      Hadwiger coefficient lends confidence to the numerous results that have been
      previously obtained within standard morphological thermodynamics. 

PMID- 25381495
TI  - Communication: Ultrafast time-resolved ion photofragmentation spectroscopy of
      photoionization-induced proton transfer in phenol-ammonia complex.
AB  - Photoionization-induced proton transfer (PT) in phenol-ammonia (PhOH-NH3) complex
      has been studied using ultrafast time-resolved ion photofragmentation
      spectroscopy. Neutral PhOH-NH3 complexes prepared in a free jet are photoionized
      by femtosecond [1+1] resonance-enhanced multiphoton ionization via the S1 state,
      and the subsequent dynamics occurring in the cations is probed by delayed pulses
      that result in ion fragmentation. The observed temporal evolutions of the
      photofragmentation spectra are consistent with an intracomplex PT reaction. The
      experiments revealed that PT in [PhOH-NH3](+) cation proceeds in two distinct
      steps: an initial impulsive wave-packet motion in ~70 fs followed by a slower
      relaxation of about 1 ps that stabilizes the system into the final PT
      configuration. These results indicate that for a barrierless PT system, even
      though the initial PT motions are impulsive and ultrafast, the reaction may take
      a much longer time scale to complete.

PMID- 25381496
TI  - Periodic subsystem density-functional theory.
AB  - By partitioning the electron density into subsystem contributions, the Frozen
      Density Embedding (FDE) formulation of subsystem Density Functional Theory (DFT)
      has recently emerged as a powerful tool for reducing the computational scaling of
      Kohn-Sham DFT. To date, however, FDE has been employed to molecular systems only.
      Periodic systems, such as metals, semiconductors, and other crystalline solids
      have been outside the applicability of FDE, mostly because of the lack of a
      periodic FDE implementation. To fill this gap, in this work we aim at extending
      FDE to treat subsystems of molecular and periodic character. This goal is
      achieved by a dual approach. On one side, the development of a theoretical
      framework for periodic subsystem DFT. On the other, the realization of the method
      into a parallel computer code. We find that periodic FDE is capable of
      reproducing total electron densities and (to a lesser extent) also interaction
      energies of molecular systems weakly interacting with metallic surfaces. In the
      pilot calculations considered, we find that FDE fails in those cases where there
      is appreciable density overlap between the subsystems. Conversely, we find FDE to
      be in semiquantitative agreement with Kohn-Sham DFT when the inter-subsystem
      density overlap is low. We also conclude that to make FDE a suitable method for
      describing molecular adsorption at surfaces, kinetic energy density functionals
      that go beyond the GGA level must be employed. 

PMID- 25381494
TI  - Communication: Smoothing out excited-state dynamics: analytical gradients for
      dynamically weighted complete active space self-consistent field.
AB  - State averaged complete active space self-consistent field (SA-CASSCF) is a
      workhorse for determining the excited-state electronic structure of molecules,
      particularly for states with multireference character; however, the method
      suffers from known issues that have prevented its wider adoption. One issue is
      the presence of discontinuities in potential energy surfaces when a state that is
      not included in the state averaging crosses with one that is. In this
      communication I introduce a new dynamical weight with spline (DWS) scheme that
      mimics SA-CASSCF while removing energy discontinuities due to unweighted state
      crossings. In addition, analytical gradients for DWS-CASSCF (and other
      dynamically weighted schemes) are derived for the first time, enabling energy
      conserving excited-state ab initio molecular dynamics in instances where SA
      CASSCF fails. 

PMID- 25381497
TI  - Direct experimental determination of spectral densities of molecular complexes.
AB  - Determining the spectral density of a molecular system immersed in a proteomic
      scaffold and in contact to a solvent is a fundamental challenge in the coarse
      grained description of, e.g., electron and energy transfer dynamics. Once the
      spectral density is characterized, all the time scales are captured and no
      artificial separation between fast and slow processes need to be invoked. Based
      on the fluorescence Stokes shift function, we utilize a simple and robust
      strategy to extract the spectral density of a number of molecular complexes from
      available experimental data. Specifically, we show that experimental data for dye
      molecules in several solvents, amino acid proteins in water, and some
      photochemical systems (e.g., rhodopsin and green fluorescence proteins), are well
      described by a three-parameter family of sub-Ohmic spectral densities that are
      characterized by a fast initial Gaussian-like decay followed by a slow algebraic
      like decay rate at long times. 

PMID- 25381498
TI  - A multi-species exchange model for fully fluctuating polymer field theory
      simulations.
AB  - Field-theoretic models have been used extensively to study the phase behavior of
      inhomogeneous polymer melts and solutions, both in self-consistent mean-field
      calculations and in numerical simulations of the full theory capturing
      composition fluctuations. The models commonly used can be grouped into two
      categories, namely, species models and exchange models. Species models involve
      integrations of functionals that explicitly depend on fields originating both
      from species density operators and their conjugate chemical potential fields. In
      contrast, exchange models retain only linear combinations of the chemical
      potential fields. In the two-component case, development of exchange models has
      been instrumental in enabling stable complex Langevin (CL) simulations of the
      full complex-valued theory. No comparable stable CL approach has yet been
      established for field theories of the species type. Here, we introduce an
      extension of the exchange model to an arbitrary number of components, namely, the
      multi-species exchange (MSE) model, which greatly expands the classes of soft
      material systems that can be accessed by the complex Langevin simulation
      technique. We demonstrate the stability and accuracy of the MSE-CL sampling
      approach using numerical simulations of triblock and tetrablock terpolymer melts,
      and tetrablock quaterpolymer melts. This method should enable studies of a wide
      range of fluctuation phenomena in multiblock/multi-species polymer blends and
      composites. 

PMID- 25381499
TI  - Strong-field ionization rates of linear polyenes simulated with time-dependent
      configuration interaction with an absorbing potential.
AB  - The strong field ionization rates for ethylene, trans 1,3-butadiene, and
      trans,trans 1,3,5-hexatriene have been calculated using time-dependent
      configuration interaction with single excitations and a complex absorbing
      potential (TDCIS-CAP). The calculations used the aug-cc-pVTZ basis set with a
      large set of diffuse functions (3 s, 2 p, 3 d, and 1 f) on each atom. The
      absorbing boundary was placed 3.5 times the van der Waals radius from each atom.
      The simulations employed a seven-cycle cosine squared pulse with a wavelength of
      800 nm. Ionization rates were calculated for intensities ranging from 0.3 *
      10(14) W/cm(2) to 3.5 * 10(14) W/cm(2). Ionization rates along the molecular axis
      increased markedly with increasing conjugation length. By contrast, ionization
      rates perpendicular to the molecular axis were almost independent of the
      conjugation length. 

PMID- 25381500
TI  - Dynamic mesoscale model of dipolar fluids via fluctuating hydrodynamics.
AB  - Fluctuating hydrodynamics (FHD) is a general framework of mesoscopic modeling and
      simulation based on conservational laws and constitutive equations of linear and
      nonlinear responses. However, explicit representation of electrical forces in FHD
      has yet to appear. In this work, we devised an Ansatz for the dynamics of dipole
      moment densities that is linked with the Poisson equation of the electrical
      potential phi in coupling to the other equations of FHD. The resulting phi-FHD
      equations then serve as a platform for integrating the essential forces,
      including electrostatics in addition to hydrodynamics, pressure-volume equation
      of state, surface tension, and solvent-particle interactions that govern the
      emergent behaviors of molecular systems at an intermediate scale. This unique
      merit of phi-FHD is illustrated by showing that the water dielectric function and
      ion hydration free energies in homogeneous and heterogenous systems can be
      captured accurately via the mesoscopic simulation. Furthermore, we show that the
      field variables of phi-FHD can be mapped from the trajectory of an all-atom
      molecular dynamics simulation such that model development and parametrization can
      be based on the information obtained at a finer-grained scale. With the
      aforementioned multiscale capabilities and a spatial resolution as high as 5 A,
      the phi-FHD equations represent a useful semi-explicit solvent model for the
      modeling and simulation of complex systems, such as biomolecular machines and
      nanofluidics. 

PMID- 25381501
TI  - Quantum chemical approach for condensed-phase thermochemistry: proposal of a
      harmonic solvation model.
AB  - We propose a novel quantum chemical method, called the harmonic solvation model
      (HSM), for calculating thermochemical parameters in the condensed phase,
      particularly in the liquid phase. The HSM represents translational and rotational
      motions of a solute as vibrations interacting with a cavity wall of solvent
      molecules. As examples, the HSM and the ideal-gas model (IGM) were used for the
      standard formation reaction of liquid water, combustion reactions of liquid
      formic acid, methanol, and ethanol, vapor-liquid equilibration of water and
      ethanol, and dissolution of gaseous CO2 in water. The numerical results confirmed
      the reliability and applicability of the HSM. In particular, the temperature
      dependence of the Gibbs energy of liquid molecules was accurately reproduced by
      the HSM; for example, the boiling point of water was reasonably determined using
      the HSM, whereas the conventional IGM treatment failed to obtain a crossing of
      the two Gibbs energy curves for gaseous and liquid water. 

PMID- 25381502
TI  - A coarse-graining approach for molecular simulation that retains the dynamics of
      the all-atom reference system by implementing hydrodynamic interactions.
AB  - We report on a new approach for deriving coarse-grained intermolecular forces
      that retains the frictional contribution that is often discarded by conventional
      coarse-graining methods. The approach is tested for water and an aqueous glucose
      solution, and the results from the new implementation for coarse-grained
      molecular dynamics simulation show remarkable agreement with the dynamics
      obtained from reference all-atom simulations. The agreement between the
      structural properties observed in the coarse-grained and all-atom simulations is
      also preserved. We discuss how this approach may be applied broadly to any
      existing coarse-graining method where the coarse-grained models are rigorously
      derived from all-atom reference systems. 

PMID- 25381503
TI  - Simplified continuum solvent model with a smooth cavity based on volumetric data.
AB  - We present a continuum solvent model (CSM) with a smooth cavity for the
      application in grid-based electronic structure methods. The cavity is identified
      with the inherently smooth distribution function of a binary mixture at infinite
      dilution. We obtain a cavity model based on atomic van der Waals radii and one
      free parameter controlling the overall size. This single parameter is sufficient
      to adequately reproduce experimental partial molar volumes. The CSM based on this
      cavity is of similar accuracy in the prediction of aqueous solvation Gibbs
      energies of small neutral molecules and ions as other CSMs with a smooth cavity.
      We apply the model to systems in non-aqueous solution, i.e.,
      spiropyran/merocyanin energetics, a proton transfer reaction in dimethyl
      sulfoxide, and the electrostatic screening of charged gold clusters in an ionic
      liquid. 

PMID- 25381504
TI  - On the description of conical intersections--a continuous representation of the
      local topography of seams of conical intersection of three or more electronic
      states: a generalization of the two state result.
AB  - For conical intersections of two states (I,J = I + 1) the vectors defining the
      branching or g-h plane, the energy difference gradient vector g(I,J), and the
      interstate coupling vector h(I,J), can be made orthogonal by a one parameter
      rotation of the degenerate electronic eigenstates. The representation obtained
      from this rotation is used to construct the parameters that describe the vicinity
      of the conical intersection seam, the conical parameters, s(x)(I,J)(R),
      s(y)(I,J)(R), g(I,J)(R), and h(I,J)(R). As a result of the orthogonalization
      these parameters can be made continuous functions of R, the internuclear
      coordinates. In this work we generalize this notion to construct continuous
      parametrizations of conical intersection seams of three or more states. The
      generalization derives from a recently introduced procedure for using non
      degenerate electronic states to construct coupled diabatic states that represent
      adiabatic states coupled by conical intersections. The procedure is illustrated
      using the seam of conical intersections of three states in parazolyl as an
      example.

PMID- 25381505
TI  - Recognizing molecular patterns by machine learning: an agnostic structural
      definition of the hydrogen bond.
AB  - The concept of chemical bonding can ultimately be seen as a rationalization of
      the recurring structural patterns observed in molecules and solids. Chemical
      intuition is nothing but the ability to recognize and predict such patterns, and
      how they transform into one another. Here, we discuss how to use a computer to
      identify atomic patterns automatically, so as to provide an algorithmic
      definition of a bond based solely on structural information. We concentrate in
      particular on hydrogen bonding--a central concept to our understanding of the
      physical chemistry of water, biological systems, and many technologically
      important materials. Since the hydrogen bond is a somewhat fuzzy entity that
      covers a broad range of energies and distances, many different criteria have been
      proposed and used over the years, based either on sophisticate electronic
      structure calculations followed by an energy decomposition analysis, or on
      somewhat arbitrary choices of a range of structural parameters that is deemed to
      correspond to a hydrogen-bonded configuration. We introduce here a definition
      that is univocal, unbiased, and adaptive, based on our machine-learning analysis
      of an atomistic simulation. The strategy we propose could be easily adapted to
      similar scenarios, where one has to recognize or classify structural patterns in
      a material or chemical compound.

PMID- 25381506
TI  - Complete active space second-order perturbation theory with cumulant
      approximation for extended active-space wavefunction from density matrix
      renormalization group.
AB  - We report an extension of our previous development that incorporated quantum
      chemical density matrix renormalization group (DMRG) into the complete active
      space second-order perturbation theory (CASPT2) [Y. Kurashige and T. Yanai, J.
      Chem. Phys. 135, 094104 (2011)]. In the previous study, the combined theory,
      referred to as DMRG-CASPT2, was built upon the use of pseudo-canonical molecular
      orbitals (PCMOs) for one-electron basis. Within the PCMO basis, the construction
      of the four-particle reduced density matrix (4-RDM) using DMRG can be greatly
      facilitated because of simplicity in the multiplication of 4-RDM and diagonal
      Fock matrix in the CASPT2 equation. In this work, we develop an approach to use
      more suited orbital basis in DMRG-CASPT2 calculations, e.g., localized molecular
      orbitals, in order to extend the domain of applicability. Because the
      multiplication of 4-RDM and generalized Fock matrix is no longer simple in
      general orbitals, an approximation is made to it using the cumulant
      reconstruction neglecting higher-particle cumulants. Also, we present the details
      of the algorithm to compute 3-RDM of the DMRG wavefunction as an extension of the
      2-RDM algorithm of Zgid et al. [J. Chem. Phys. 128, 144115 (2008)] and Chan et
      al. [J. Chem. Phys. 128, 144117 (2008)]. The performance of the extended DMRG
      CASPT2 approach was examined for large-scale multireference systems, such as low
      lying excited states of long-chain polyenes and isomerization potential of
      {[Cu(NH3)3]2O2}(2+). 

PMID- 25381507
TI  - Entropic penalties in circular DNA assembly.
AB  - The thermodynamic properties of DNA circular molecules are investigated by a new
      path integral computational method which treats in the real space the fundamental
      forces stabilizing the molecule. The base pair and stacking contributions to the
      classical action are evaluated separately by simulating a broad ensemble of
      twisted conformations. We obtain, for two short sequences, a free energy
      landscape with multiple wells corresponding to the most convenient values of
      helical repeat. Our results point to a intrinsic flexibility of the circular
      structures in which the base pair fluctuations move the system from one well to
      the next thus causing the local unwinding of the helix. The latter is more
      pronounced in the shorter sequence whose cyclization causes a higher bending
      stress. The entropic reductions associated to the formation of the ordered
      helicoidal structure are estimated. 

PMID- 25381508
TI  - Observations of Dicke narrowing and speed dependence in air-broadened CO2
      lineshapes near 2.06 MUm.
AB  - Frequency-stabilized cavity ring-down spectroscopy was used to study CO2
      lineshapes in the (20013) <- (00001) band centered near 2.06 MUm. Two
      rovibrational transitions were chosen for this study to measure non-Voigt
      collisional effects for air-broadened lines over the pressure range of 7 kPa-28
      kPa. Lineshape analysis for both lines revealed evidence of simultaneous Dicke
      (collisional) narrowing and speed-dependent effects that would introduce biases
      exceeding 2% in the retrieved air-broadening parameters if not incorporated in
      the modeling of CO2 lineshapes. Additionally, correlations between velocity- and
      phase/state changing collisions greatly reduced the observed Dicke narrowing
      effect. As a result, it was concluded that the most appropriate line profile for
      modeling CO2 lineshapes near 2.06 MUm was the correlated speed-dependent Nelkin
      Ghatak profile, which includes all of the physical effects mentioned above and
      leads to a consistent set of line shape parameters that are linear with gas
      pressure.

PMID- 25381509
TI  - High resolution spectral analysis of oxygen. IV. Energy levels, partition sums,
      band constants, RKR potentials, Franck-Condon factors involving the X3Sigmag-,
      a1Deltag and b1Sigmag+ states.
AB  - We have updated the isotopically invariant Dunham fit of O2 with newly reported
      literature transitions to derive (1) the energy levels, partition sums, band-by
      band molecular constants, and RKR potentials for the X(3)Sigmag(-), a(1)Deltag,
      and b(1)Sigmag(+) states of the six O2 isotopologues: (16)O(16)O, (16)O(17)O,
      (16)O(18)O, (17)O(17)O, (17)O(18)O, and (18)O(18)O; (2) Franck-Condon factors for
      their a(1)Deltag-X(3)Sigmag(-), b(1)Sigmag(+)-X(3)Sigmag(-), and a(1)Deltag
      b(1)Sigmag(+) band systems. This new spectroscopic parameterization characterizes
      all known transitions within and between the X(3)Sigmag(-), a(1)Deltag, and
      b(1)Sigmag(+) states within experimental uncertainty and can be used for accurate
      predictions of as yet unmeasured transitions. All of these results are necessary
      to provide a consistent linelist of all transitions which will be reported in a
      followup paper.

PMID- 25381510
TI  - One-photon mass-analyzed threshold ionization (MATI) spectroscopy of pyridine:
      determination of accurate ionization energy and cationic structure.
AB  - Ionization energies and cationic structures of pyridine were intensively
      investigated utilizing one-photon mass-analyzed threshold ionization (MATI)
      spectroscopy with vacuum ultraviolet radiation generated by four-wave difference
      frequency mixing in Kr. The present one-photon high-resolution MATI spectrum of
      pyridine demonstrated a much finer and richer vibrational structure than that of
      the previously reported two-photon MATI spectrum. From the MATI spectrum and
      photoionization efficiency curve, the accurate ionization energy of the ionic
      ground state of pyridine was confidently determined to be 73,570 +/- 6 cm(-1)
      (9.1215 +/- 0.0007 eV). The observed spectrum was almost completely assigned by
      utilizing Franck-Condon factors and vibrational frequencies calculated through
      adjustments of the geometrical parameters of cationic pyridine at the B3LYP/cc
      pVTZ level. A unique feature unveiled through rigorous analysis was the prominent
      progression of the 10 vibrational mode, which corresponds to in-plane ring
      bending, and the combination of other totally symmetric fundamentals with the
      ring bending overtones, which contribute to the geometrical change upon
      ionization. Notably, the remaining peaks originate from the upper electronic
      state ((2)A2), as predicted by high-resolution photoelectron spectroscopy studies
      and symmetry-adapted cluster configuration interaction calculations. Based on the
      quantitatively good agreement between the experimental and calculated results, it
      was concluded that upon ionization the pyridine cation in the ground electronic
      state should have a planar structure of C(2v) symmetry through the C-N axis.

PMID- 25381511
TI  - Tip-contact related low-bias negative differential resistance and rectifying
      effects in benzene-porphyrin-benzene molecular junctions.
AB  - The electronic transport properties of benzene-porphyrin-benzene (BPB) molecules
      coupled to gold (Au) electrodes were investigated. By successively removing the
      front-end Au atoms, several BPB junctions with different molecule-electrode
      contact symmetries were constructed. The calculated current-voltage (I-V) curves
      depended strongly on the contact configurations between the BPB molecules and the
      Au electrodes. In particular, a significant low-voltage negative differential
      resistance effect appeared at -0.3 V in the junctions with pyramidal electrodes
      on both sides. Along with the breaking of this tip-contact symmetry, the low-bias
      negative differential resistance effect gradually disappeared. This tip-contact
      may be ideal for use in the design of future molecular devices because of its
      similarity with experimental processes. 

PMID- 25381512
TI  - Theoretical spectroscopic characterization of the ArBeO complex.
AB  - Using the recently developed explicitly correlated coupled cluster method in
      connection with the aug-cc-pVTZ basis set, we generated the three-dimensional
      potential energy surface (3D-PES) of the ground state of the Ar-BeO complex. This
      PES covers the regions of the global and local minima, the saddle point, and the
      dissociation of the complex. The PES is also used for the calculation of the
      rovibrational spectrum up to the dissociation limit. The high density of levels
      which is observed favors the mixing of the states and hence the occurrence of
      anharmonic resonances. The wavefunctions of the high rovibrational levels exhibit
      large amplitude motions in addition to strong anharmonic resonances. Our
      theoretical spectrum should be helpful in identifying the van der Waals modes of
      this complex in laboratory. 

PMID- 25381513
TI  - Femtosecond time-resolved XUV + UV photoelectron imaging of pure helium
      nanodroplets.
AB  - Liquid helium nanodroplets, consisting of on average 2 * 10(6) atoms, are
      examined using femtosecond time-resolved photoelectron imaging. The droplets are
      excited by an extreme ultraviolet light pulse centered at 23.7 eV photon energy,
      leading to states within a band that is associated with the 1s3p and 1s4p Rydberg
      levels of free helium atoms. The initially excited states and subsequent
      relaxation dynamics are probed by photoionizing transient species with a 3.2 eV
      pulse and using velocity map imaging to measure time-dependent photoelectron
      kinetic energy distributions. Significant differences are seen compared to
      previous studies with a lower energy (1.6 eV) probe pulse. Three distinct time
      dependent signals are analyzed by global fitting. A broad intense signal,
      centered at an electron kinetic energy (eKE) of 2.3 eV, grows in faster than the
      experimental time resolution and decays in ~100 fs. This feature is attributed to
      the initially excited droplet state. A second broad transient feature, with eKE
      ranging from 0.5 to 4 eV, appears at a rate similar to the decay of the initially
      excited state and is attributed to rapid atomic reconfiguration resulting in
      Franck-Condon overlap with a broader range of cation geometries, possibly
      involving formation of a Rydberg-excited (He(n))* core within the droplet. An
      additional relaxation pathway leads to another short-lived feature with vertical
      binding energies ?2.4 eV, which is identified as a transient population within
      the lower-lying 1s2p Rydberg band. Ionization at 3.2 eV shows an enhanced
      contribution from electronically excited droplet states compared to ejected
      Rydberg atoms, which dominate at 1.6 eV. This is possibly the result of increased
      photoelectron generation from the bulk of the droplet by the more energetic probe
      photons.

PMID- 25381514
TI  - Slow photoelectron velocity-map imaging spectroscopy of the Fe3O- and Co3O-
      anions.
AB  - We report high-resolution photoelectron spectra of the transition metal suboxide
      clusters Fe3O(-) and Co3O(-). The combination of slow electron velocity-map
      imaging and cryogenic cooling yields vibrationally well-resolved spectra, from
      which we obtain precise values of 1.4408(3) and 1.3951(4) eV for the electron
      affinities of Fe3O and Co3O. Several vibrational frequencies of the neutral
      ground state Fe3O and Co3O clusters are assigned for the first time, and a low
      lying excited state of Fe3O is observed. The experimental results are compared
      with density functional electronic structure calculations and Franck-Condon
      spectral simulations, enabling identification of the structural isomer and
      electronic states. As has been found in photoelectron spectra of other trimetal
      oxo species, Fe3O(0/-) and Co3O(0/-) are assigned to a MU2-oxo isomer with planar
      C(2v) symmetry. We identify the ground states of Fe3O(-) and Co3O(-) as (12)A1
      and (9)B2 states, respectively. From these states we observe photodetachment to
      the (11)B2 ground and (13)A1 excited states of Fe3O, as well as to the (8)A1
      ground state of Co3O.

PMID- 25381515
TI  - A new potential energy surface and microwave and infrared spectra of the He-OCS
      complex.
AB  - A new high quality potential energy surface for the He-OCS van der Waals complex
      was calculated using the CCSD(T) method and avqz+33221 basis set. It is found
      that the global minimum energy is -51.33 cm(-1) at R(e) = 6.30a0 and theta(e) =
      110.0 degrees , the shallower minimum is located at R = 8.50a0 and theta = 0
      degrees  with well depth -32.26 cm(-1). Using the fitted potential energy
      surface, we have calculated bound energy levels of the He-OCS, He-O(13)CS, He
      OC(34)S, and (3)He-OCS complexes. The theoretical results are all in better
      agreement compared to previous theoretical work.

PMID- 25381516
TI  - The interaction of OH(X2Pi) with H2: ab initio potential energy surfaces and
      bound states.
AB  - For the interaction of OH(X(2)Pi) with H2, under the assumption of fixed OH and
      H2 bond distances, we have determined two new sets of four-dimensional ab initio
      potential energy surfaces (PES's). The first set of PES's was computed with the
      multi-reference configuration interaction method [MRCISD+Q(Davidson)], and the
      second set with an explicitly correlated coupled cluster method [RCCSD(T)-F12a]
      sampling the subset of geometries possessing a plane of symmetry. Both sets of
      PES's are fit to an analytical form suitable for bound state and scattering
      calculations. The CCSD(T) dissociation energies (D0) of the OH-para-H2 and the OH
      ortho-H2 complexes are computed to be 36.1 and 53.7 cm(-1). The latter value is
      in excellent agreement with the experimental value of 54 cm(-1). 

PMID- 25381518
TI  - Stereo-selective partitioning of translation-to-internal energy conversion in gas
      ensembles.
AB  - A recent computational study of translation-to-internal energy transfer to H2 (v
      = 0,j = 0), hereinafter denoted H2 (0;0), in a bath of H atoms [A. J. McCaffery
      and R. J. Marsh, J. Chem. Phys. 139, 234310 (2013)] revealed an unexpected energy
      partitioning in which the H2 vibrational temperature greatly exceeds that of
      rotation. This occurs despite rotation and vibration distributions being close to
      Boltzmann from early in ensemble evolution. In this work, the study is extended
      to include H2 (0;0), O2 (0;0), and HF (0;0) in a wide range of atomic bath gases
      comprising some 22 ensembles in all. Translation-to-internal energy conversion in
      the systems studied was found to be relatively inefficient, falling approximately
      with (?MU')(-1) as bath gas mass increases, where MU' is the reduced mass of the
      diatomic-bath gas pair. In all 22 systems studied, T(v) exceeds T(r)--by a factor
      > 4 for some pairs. Analysis of the constraints that influence (0;0) -> (1;j)
      excitation for each diatomic-atom pair in momentum-angular momentum space
      demonstrates that a vibrational preference results from energy constraints that
      limit permitted collision trajectories to those of low effective impact
      parameter, i.e., to those that are axial or near axial on impact with the Newton
      surface. This implies that a steric constraint is an inherent feature of
      vibration-rotation excitation and arises because momentum and energy barriers
      must be overcome before rotational states may be populated in the higher
      vibrational level.

PMID- 25381517
TI  - Observation in the gas phase of the ligation of 1-methylimidazole to hemoprotein
      mimics.
AB  - Hemoprotein mimics, cobalt picket fence porphyrins have been prepared in the gas
      phase as neutral molecules for the first time. Their ligation properties have
      been studied with 1-methylimidazole and compared with those of other cobalt
      porphyrins, tetraphenyl porphyrin, and cobalt protoporphyrin IX chloride, in view
      of studying the sterical properties of the ligation. It is shown that the cobalt
      picket fence porphyrin can only accept one 1-methylimidazole ligand in contrast
      to less sterically crowded porphyrins like cobalt tetraphenylporphyrin that
      present two accessible ligation sites. The femtosecond dynamics of these ligated
      systems have been studied after excitation at 400 nm, in comparison with the
      unligated ones. The observed transients are formed in much shorter times, 30 fs
      for the ligated species, as compared to free species (100 fs), supporting the
      porphyrin to metal charge transfer nature of these transients. The similar decays
      of the ligated transients <1 ps reveal the absence of photodissociation of the
      cobalt-1-methylimidazole bond at this step of evolution. 

PMID- 25381519
TI  - Tunneling splitting in double-proton transfer: direct diagonalization results for
      porphycene.
AB  - Zero-point and excited level splittings due to double-proton tunneling are
      calculated for porphycene and the results are compared with experiment. The
      calculation makes use of a multidimensional imaginary-mode Hamiltonian,
      diagonalized directly by an effective reduction of its dimensionality. Porphycene
      has a complex potential energy surface with nine stationary configurations that
      allow a variety of tunneling paths, many of which include classically accessible
      regions. A symmetry-based approach is used to show that the zero-point level,
      although located above the cis minimum, corresponds to concerted tunneling along
      a direct trans - trans path; a corresponding cis - cis path is predicted at
      higher energy. This supports the conclusion of a previous paper [Z. Smedarchina,
      W. Siebrand, and A. Fernandez-Ramos, J. Chem. Phys. 127, 174513 (2007)] based on
      the instanton approach to a model Hamiltonian of correlated double-proton
      transfer. A multidimensional tunneling Hamiltonian is then generated, based on a
      double-minimum potential along the coordinate of concerted proton motion, which
      is newly evaluated at the RI-CC2/cc-pVTZ level of theory. To make it suitable for
      diagonalization, its dimensionality is reduced by treating fast weakly coupled
      modes in the adiabatic approximation. This results in a coordinate-dependent mass
      of tunneling, which is included in a unique Hermitian form into the kinetic
      energy operator. The reduced Hamiltonian contains three symmetric and one
      antisymmetric mode coupled to the tunneling mode and is diagonalized by a
      modified Jacobi-Davidson algorithm implemented in the Jadamilu software for
      sparse matrices. The results are in satisfactory agreement with the observed
      splitting of the zero-point level and several vibrational fundamentals after a
      partial reassignment, imposed by recently derived selection rules. They also
      agree well with instanton calculations based on the same Hamiltonian. 

PMID- 25381520
TI  - The role of the transition state in polyatomic reactions: initial state-selected
      reaction probabilities of the H + CH4 -> H2 + CH3 reaction.
AB  - Full-dimensional calculations of initial state-selected reaction probabilities on
      an accurate ab initio potential energy surface (PES) have been communicated
      recently [R. Welsch and U. Manthe, J. Chem. Phys. 141, 051102 (2014)]. These
      calculations use the quantum transition state concept, the multi-layer multi
      configurational time-dependent Hartree approach, and graphics processing units to
      speed up the potential evaluation. Here further results of these calculations and
      an extended analysis are presented. State-selected reaction probabilities are
      given for many initial ro-vibrational states. The role of the vibrational states
      of the activated complex is analyzed in detail. It is found that rotationally
      cold methane mainly reacts via the ground state of the activated complex while
      rotationally excited methane mostly reacts via H-H-CH3-bending excited states of
      the activated complex. Analyzing the different contributions to the reactivity of
      the vibrationally states of methane, a complex pattern is found. Comparison with
      initial state-selected reaction probabilities computed on the semi-empirical
      Jordan-Gilbert PES reveals the dependence of the results on the specific PES. 

PMID- 25381522
TI  - A coupled-cluster study of photodetachment cross sections of closed-shell anions.
AB  - We investigate the performance of Stieltjes Imaging applied to Lanczos pseudo
      spectra generated at the coupled cluster singles and doubles, coupled cluster
      singles and approximate iterative doubles and coupled cluster singles levels of
      theory in modeling the photodetachment cross sections of the closed shell anions
      H(-), Li(-), Na(-), F(-), Cl(-), and OH(-). The accurate description of double
      excitations is found to play a much more important role than in the case of
      photoionization of neutral species. 

PMID- 25381521
TI  - The effect of hydrogen bonding on torsional dynamics: a combined far-infrared jet
      and matrix isolation study of methanol dimer.
AB  - The effect of strong intermolecular hydrogen bonding on torsional degrees of
      freedom is investigated by far-infrared absorption spectroscopy for different
      methanol dimer isotopologues isolated in supersonic jet expansions or embedded in
      inert neon matrices at low temperatures. For the vacuum-isolated and Ne-embedded
      methanol dimer, the hydrogen bond OH librational mode of the donor subunit is
      finally observed at ~560 cm(-1), blue-shifted by more than 300 cm(-1) relative to
      the OH torsional fundamental of the free methanol monomer. The OH torsional mode
      of the acceptor embedded in neon is observed at ~286 cm(-1). The experimental
      findings are held against harmonic predictions from local coupled-cluster methods
      with single and double excitations and a perturbative treatment of triple
      excitations [LCCSD(T)] and anharmonic. VPT2 corrections at canonical MP2 and
      density functional theory (DFT) levels in order to quantify the contribution of
      vibrational anharmonicity for this important class of intermolecular hydrogen
      bond vibrational motion.

PMID- 25381523
TI  - Theoretical investigation of the relative stability of Na+He(n) (n = 2-24)
      clusters: many-body versus delocalization effects.
AB  - The solvation of the Na(+) ion in helium clusters has been studied theoretically
      using optimization methods. A many-body empirical potential was developed to
      account for Na(+)-He and polarization interactions, and the most stable
      structures of Na(+)He(n) clusters were determined using the basin-hopping method.
      Vibrational delocalization was accounted for using zero-point energy corrections
      at the harmonic or anharmonic levels, the latter being evaluated from quantum
      Monte Carlo simulations for spinless particles. From the static perspective, many
      body effects are found to play a minor role, and the structures obtained reflect
      homogeneous covering up to n = 10, followed by polyicosahedral packing above this
      size, the cluster obtained at n = 12 appearing particularly stable. The cationic
      impurity binds the closest helium atoms sufficiently to negate vibrational
      delocalization at small sizes. However, this snowball effect is obliterated
      earlier than shell completion, the nuclear wavefunctions of (4)He(n)Na(+) with n
      = 5-7, and n > 10 already exhibiting multiple inherent structures. The decrease
      in the snowball size due to many-body effects is consistent with recent mass
      spectrometry measurements.

PMID- 25381524
TI  - Theoretical description of electronically excited vinylidene up to 10 eV: first
      high level ab initio study of singlet valence and Rydberg states.
AB  - The first quantitative description of the Rydberg and valence singlet electronic
      states of vinylidene lying in the 0-10 eV region is performed by using large
      scale ab initio calculations. A deep analysis of Rydberg-valence interactions has
      been achieved thanks to the comprehensive information contained in the accurate
      Multi-Reference Configuration Interaction wavefunctions and an original
      population analysis highlighting the respective role played by orbital and state
      mixing in such interactions. The present theoretical approach is thus adequate
      for dealing with larger than diatomic Rydberg systems. The nine lowest singlet
      valence states have been optimized. Among them, some are involved in strong
      Rydberg-valence interactions in the region of the Rydberg state equilibrium
      geometry. The Rydberg states of vinylidene present a great similarity with the
      acetylene isomer, concerning their quantum defects and Rydberg molecular orbital
      character. As in acetylene, strong s-d mixing is revealed in the n = 3 s-d
      supercomplex. Nevertheless, unlike in acetylene, the close-energy of the two
      vinylidene ionic cores (2)A1 and (2)B1 results into two overlapped Rydberg
      series. These Rydberg series exhibit local perturbations when an accidental
      degeneracy occurs between them and results in avoided crossings. In addition,
      some Deltal = 1 (s-p and p-d) mixings arise for some Rydberg states and are
      rationalized in term of electrostatic interaction from the electric dipole moment
      of the ionic core. The strongest dipole moment of the (2)B1 cationic state also
      stabilizes the lowest members of the n = 3 Rydberg series converging to this
      excited state, as compared to the adjacent series converging toward the (2)A1
      ionic ground state. The overall energies of vinylidene Rydberg states lie above
      their acetylene counterpart. Finally, predictions for optical transitions in
      singlet vinylidene are suggested for further experimental spectroscopic
      characterization of vinylidene. 

PMID- 25381525
TI  - Structural behavior and dynamics of an anomalous fluid between attractive and
      repulsive walls: templating, molding, and superdiffusion.
AB  - Confinement can modify the dynamics, the thermodynamics, and the structural
      properties of liquid water, the prototypical anomalous liquid. By considering a
      generic model for anomalous liquids, suitable for describing solutions of
      globular proteins, colloids, or liquid metals, we study by molecular dynamics
      simulations the effect that an attractive wall with structure and a repulsive
      wall without structure have on the phases, the crystal nucleation, and the
      dynamics of the fluid. We find that at low temperatures the large density of the
      attractive wall induces a high-density, high-energy structure in the first layer
      ("templating" effect). In turn, the first layer induces a "molding" effect on the
      second layer determining a structure with reduced energy and density, closer to
      the average density of the system. This low-density, low-energy structure
      propagates further through the layers by templating effect and can involve all
      the existing layers at the lowest temperatures investigated. Therefore, although
      the high-density, high-energy structure does not self-reproduce further than the
      first layer, the structured wall can have a long-range influence thanks to a
      sequence of templating, molding, and templating effects through the layers. We
      find that the walls also have an influence on the dynamics of the liquid, with a
      stronger effect near the attractive wall. In particular, we observe that the
      dynamics is largely heterogeneous (i) among the layers, as a consequence of the
      sequence of structures caused by the walls presence, and (ii) within the same
      layer, due to superdiffusive liquid veins within a frozen matrix of particles
      near the walls at low temperature and high density. Hence, the partial freezing
      of the first layer does not correspond necessarily to an effective reduction of
      the channel's section in terms of transport properties, as suggested by other
      authors. 

PMID- 25381526
TI  - Self-consistent elastic continuum theory of degenerate, equilibrium aperiodic
      solids.
AB  - We show that the vibrational response of a glassy liquid at finite frequencies
      can be described by continuum mechanics despite the vast degeneracy of the
      vibrational ground state; standard continuum elasticity assumes a unique ground
      state. The effective elastic constants are determined by the bare elastic
      constants of individual free energy minima of the liquid, the magnitude of built
      in stress, and temperature, analogously to how the dielectric response of a polar
      liquid is determined by the dipole moment of the constituent molecules and
      temperature. In contrast with the dielectric constant--which is enhanced by
      adding polar molecules to the system--the elastic constants are down-renormalized
      by the relaxation of the built-in stress. The renormalization flow of the elastic
      constants has three fixed points, two of which are trivial and correspond to the
      uniform liquid state and an infinitely compressible solid, respectively. There is
      also a nontrivial fixed point at the Poisson ratio equal to 1/5, which
      corresponds to an isospin-like degeneracy between shear and uniform deformation.
      The present description predicts a discontinuous jump in the (finite frequency)
      shear modulus at the crossover from collisional to activated transport,
      consistent with the random first order transition theory.

PMID- 25381527
TI  - The structure of CO2 hydrate between 0.7 and 1.0 GPa.
AB  - A deuterated sample of CO2 structure I (sI) clathrate hydrate (CO2.8.3 D2O) has
      been formed and neutron diffraction experiments up to 1.0 GPa at 240 K were
      performed. The sI CO2 hydrate transformed at 0.7 GPa into the high pressure phase
      that had been observed previously by Hirai et al. [J. Phys. Chem. 133, 124511
      (2010)] and Bollengier et al. [Geochim. Cosmochim. Acta 119, 322 (2013)], but
      which had not been structurally identified. The current neutron diffraction data
      were successfully fitted to a filled ice structure with CO2 molecules filling the
      water channels. This CO2+water system has also been investigated using classical
      molecular dynamics and density functional ab initio methods to provide additional
      characterization of the high pressure structure. Both models indicate the water
      network adapts a MH-III "like" filled ice structure with considerable disorder of
      the orientations of the CO2 molecule. Furthermore, the disorder appears to be a
      direct result of the level of proton disorder in the water network. In contrast
      to the conclusions of Bollengier et al., our neutron diffraction data show that
      the filled ice phase can be recovered to ambient pressure (0.1 MPa) at 96 K, and
      recrystallization to sI hydrate occurs upon subsequent heating to 150 K, possibly
      by first forming low density amorphous ice. Unlike other clathrate hydrate
      systems, which transform from the sI or sII structure to the hexagonal structure
      (sH) then to the filled ice structure, CO2 hydrate transforms directly from the
      sI form to the filled ice structure.

PMID- 25381528
TI  - Triplet correlation functions in liquid water.
AB  - Triplet correlations have been shown to play a crucial role in the transformation
      of simple liquids to anomalous tetrahedral fluids [M. Singh, D. Dhabal, A. H.
      Nguyen, V. Molinero, and C. Chakravarty, Phys. Rev. Lett. 112, 147801 (2014)].
      Here we examine triplet correlation functions for water, arguably the most
      important tetrahedral liquid, under ambient conditions, using configurational
      ensembles derived from molecular dynamics (MD) simulations and reverse Monte
      Carlo (RMC) datasets fitted to experimental scattering data. Four different RMC
      data sets with widely varying hydrogen-bond topologies fitted to neutron and x
      ray scattering data are considered [K. T. Wikfeldt, M. Leetmaa, M. P. Ljungberg,
      A. Nilsson, and L. G. M. Pettersson, J. Phys. Chem. B 113, 6246 (2009)].
      Molecular dynamics simulations are performed for two rigid-body effective pair
      potentials (SPC/E and TIP4P/2005) and the monatomic water (mW) model. Triplet
      correlation functions are compared with other structural measures for
      tetrahedrality, such as the O-O-O angular distribution function and the local
      tetrahedral order distributions. In contrast to the pair correlation functions,
      which are identical for all the RMC ensembles, the O-O-O triplet correlation
      function can discriminate between ensembles with different degrees of tetrahedral
      network formation with the maximally symmetric, tetrahedral SYM dataset
      displaying distinct signatures of tetrahedrality similar to those obtained from
      atomistic simulations of the SPC/E model. Triplet correlations from the RMC
      datasets conform closely to the Kirkwood superposition approximation, while those
      from MD simulations show deviations within the first two neighbour shells. The
      possibilities for experimental estimation of triplet correlations of water and
      other tetrahedral liquids are discussed. 

PMID- 25381529
TI  - An investigation of the liquid to glass transition using integral equations for
      the pair structure of coupled replicae.
AB  - Extensive numerical solutions of the hypernetted-chain (HNC) and Rogers-Young
      (RY) integral equations are presented for the pair structure of a system of two
      coupled replicae (1 and 2) of a "soft-sphere" fluid of atoms interacting via an
      inverse-12 pair potential. In the limit of vanishing inter-replica coupling E12,
      both integral equations predict the existence of three branches of solutions: (1)
      A high temperature liquid branch (L), which extends to a supercooled regime upon
      cooling when the two replicae are kept at E12 = 0 throughout; upon separating the
      configurational and vibrational contributions to the free energy and entropy of
      the L branch, the Kauzmann temperature is located where the configurational
      entropy vanishes. (2) Starting with an initial finite coupling E12, two "glass"
      branches G1 and G2 are found below some critical temperature, which are
      characterized by a strong remnant spatial inter-replica correlation upon taking
      the limit E12 -> 0. Branch G2 is characterized by an increasing overlap order
      parameter upon cooling, and may hence be identified with the hypothetical "ideal
      glass" phase. Branch G1 exhibits the opposite trend of increasing order parameter
      upon heating; its free energy lies consistently below that of the L branch and
      above that of the G2 branch. The free energies of the L and G2 branches are found
      to intersect at an alleged "random first-order transition" (RFOT) characterized
      by weak discontinuities of the volume and entropy. The Kauzmann and RFOT
      temperatures predicted by RY differ significantly from their HNC counterparts. 

PMID- 25381530
TI  - Kinetic density functional theory of freezing.
AB  - A theory of freezing of a dense hard sphere gas is presented. Starting from a
      revised Enskog theory, hydrodynamic equations that account for non-local
      variations in the density but local variations in the flow field are derived
      using a modified Chapman Enskog procedure. These hydrodynamic equations, which
      retain structural correlations, are shown to be effectively a time dependent
      density functional theory. The ability of this theory to capture the solid liquid
      phase transition is established through analysis and numerical simulations. 

PMID- 25381531
TI  - Non-exponential relaxation, fictive temperatures, and dispersive kinetics in the
      liquid-glass-liquid transition range of acetaminophen, sulfathiazole, and their
      mixtures.
AB  - To investigate the effects of added molecular heterogeneity on the hysteretic
      features of liquid-glass-liquid transition, we studied acetaminophen,
      sulfathiazole, and three of their mixtures by calorimetry, and determined the
      T(g) and the fictive temperature, T(f), from changes in the enthalpy and entropy
      on the cooling and heating paths, as well as the non-exponential parameter,
      beta(cal). We find that, (i) T(f) for cooling is within 1-3 K of T(f) for heating
      and both are close to T(g), (ii) the closed loop entropy change in the liquid
      glass-liquid range is negligibly small, (iii) T(g) and T(f) increase on
      increasing sulfathiazole in the mixture, (iv) beta(cal) first slightly increases
      when the second component is added and then decreases, and (v) ageing causes
      deviations from a non-exponential, nonlinear behavior of the glass. In terms of
      fluctuations in a potential energy landscape, adding a solute heterogeneity would
      shift the state point to another part of the landscape with a different
      distribution of barrier heights and a different number of minima accessible to
      the state point. Part of the change in beta(cal) is attributed to hydrogen-bond
      formation between the two components. Ageing changes the relaxation times
      distribution, more at short relaxation times than at long relaxation times, and
      multiplicity of relaxation modes implied by beta(cal) < 1 indicates that each
      mode contributing to the enthalpy has its own T(g) or T(f). beta(cal) differs
      from beta(age) determined from isothermal ageing, and the distribution parameter
      of alpha-relaxation times would differ from both beta(cal) and beta(age).

PMID- 25381532
TI  - Dissociative adsorption of CH3X (X = Br and Cl) on a silicon(100) surface
      revisited by density functional theory.
AB  - During the dissociative adsorption on a solid surface, the substrate usually
      participates in a passive manner to accommodate fragments produced upon the
      cleavage of the internal bond(s) of a (transient) molecular adsorbate. This
      simple picture, however, neglects the flexibility of surface atoms. Here, we
      report a Density Functional Theory study to revisit our early studies of the
      dissociative adsorption of CH3X (X = Br and Cl) on Si(100). We have identified a
      new reaction pathway, which involves a flip of a silicon dimer; this new pathway
      agrees better with experiments. For our main exemplar of CH3Br, insights have
      been gained using a simple model that involves a three-atom reactive center, Br-C
      Si. When the silicon dimer flips, the interaction between C and Si in the Br-C-Si
      center is enhanced, evident in the increased energy-split of the frontier
      orbitals. We also examine how the dissociation dynamics of CH3Br is altered on a
      heterodimer (Si-Al, Si-P, and Si-Ge) in a Si(100) surface. In each case, we
      conclude, on the basis of computed reaction pathways, that no heterodimer
      flipping is involved before the system transverses the transition state to
      dissociative adsorption. 

PMID- 25381533
TI  - Microscopic mechanism of electron transfer through the hydrogen bonds between
      carboxylated alkanethiol molecules connected to gold electrodes.
AB  - The atomic structure and the electron transfer properties of hydrogen bonds
      formed between two carboxylated alkanethiol molecules connected to gold
      electrodes are investigated by employing the non-equilibrium Green's function
      formalism combined with density functional theory. Three types of molecular
      junctions are constructed, in which one carboxyl alkanethiol molecule contains
      two methylene, -CH2, groups and the other one is composed of one, two, or three 
      CH2 groups. Our calculations show that, similarly to the cases of isolated
      carboxylic acid dimers, in these molecular junctions the two carboxyl, -COOH,
      groups form two H-bonds resulting in a cyclic structure. When self-interaction
      corrections are explicitly considered, the calculated transmission coefficients
      of these three H-bonded molecular junctions at the Fermi level are in good
      agreement with the experimental values. The analysis of the projected density of
      states confirms that the covalent Au-S bonds localized at the molecule-electrode
      interfaces and the electronic coupling between -COOH and S dominate the low-bias
      junction conductance. Following the increase of the number of the -CH2 groups,
      the coupling between -COOH and S decreases deeply. As a result, the junction
      conductance decays rapidly as the length of the H-bonded molecules increases.
      These findings not only provide an explanation to the observed distance
      dependence of the electron transfer properties of H-bonds, but also help the
      design of molecular devices constructed through H-bonds. 

PMID- 25381534
TI  - Structure, electronic properties, and aggregation behavior of hydroxylated carbon
      nanotubes.
AB  - We present a combined experimental and theoretical study to analyze the
      structure, electronic properties, and aggregation behavior of hydroxylated
      multiwalled carbon nanotubes (OH-MWCNT). Our MWCNTs have average diameters of ~2
      nm, lengths of approximately 100-300 nm, and a hydroxyl surface coverage
      theta~0.1. When deposited on the air/water interface the OH-MWCNTs are partially
      soluble and the floating units interact and link with each other forming extended
      foam-like carbon networks. Surface pressure-area isotherms of the nanotube films
      are performed using the Langmuir balance method at different equilibration times.
      The films are transferred into a mica substrate and atomic force microscopy
      images show that the foam like structure is preserved and reveals fine details of
      their microstructure. Density functional theory calculations performed on model
      hydroxylated carbon nanotubes show that low energy atomic configurations are
      found when the OH groups form molecular islands on the nanotube's surface. This
      patchy behavior for the OH species is expected to produce nanotubes having
      reduced wettabilities, in line with experimental observations. OH doping yields
      nanotubes having small HOMO-LUMO energy gaps and generates a nanotube -> OH
      direction for the charge transfer leading to the existence of more hole carriers
      in the structures. Our synthesized OH-MWCNTs might have promising applications.

PMID- 25381535
TI  - Thermodynamic aspects of dehydrogenation reactions on noble metal surfaces.
AB  - The reaction free energy for dehydrogenation of phenol, aniline, thiophenol,
      benzoic acid, and 1,4-benzenediol on the close packed copper, silver, and gold
      surfaces has been studied by density functional theory calculations.
      Dehydrogenation of thiophenol is found to be favourable on all three surfaces
      while aniline does not dehydrogenate on any of them. For phenol, benzenediol and
      benzoic acid dehydrogenation is favourable on copper and silver only, following
      the general trend of an increasing reaction free energy when going form gold to
      silver to copper. This trend can be correlated with the changes in bond lengths
      within the molecule upon dehydrogenation. While copper is able to replace
      hydrogen, leaving small changes in the bond lengths of the aromatic ring, the
      metal-molecule bond is weaker for silver and gold, resulting in a partial loss of
      aromaticity. This difference in bond strength leads to pronounced differences in
      adsorption geometries upon multiple dehydrogenations. 

PMID- 25381536
TI  - Understanding the influence of Coulomb and dispersion interactions on the wetting
      behavior of ionic liquids.
AB  - We study the role of dispersion and electrostatic interactions in the wetting
      behavior of ionic liquids on non-ionic solid substrates. We consider a simple
      model of an ionic liquid consisting of spherical ions that interact via Lennard
      Jones and Coulomb potentials. Bulk and interfacial properties are computed for
      five fluids distinguished by the strength of the electrostatic interaction
      relative to the dispersion interaction. We employ Monte Carlo simulations and an
      interface-potential-based approach to calculate the liquid-vapor and substrate
      fluid interfacial properties. Surface tensions for each fluid are evaluated over
      a range of temperatures that spans from a reduced temperature of approximately
      0.6 to the critical point. Contact angles are calculated at select temperatures
      over a range of substrate-fluid interaction strengths that spans from the near
      drying regime to the wetting regime. We observe that an increase in the relative
      strength of Coulombic interactions between ions leads to increasing deviation
      from Guggenheim's corresponding states theory. We show how this deviation is
      related to lower values of liquid-vapor excess entropies observed for strongly
      ionic fluids. Our results show that the qualitative nature of wetting behavior is
      significantly influenced by the competition between dispersion and electrostatic
      interactions. We discuss the influence of electrostatic interactions on the
      nature of wetting and drying transitions and corresponding states like behavior
      observed for contact angles. For all of the fluids studied, we observe a
      relatively narrow range of substrate-fluid interaction strengths wherein the
      contact angle is nearly independent of temperature. The influence of the ionic
      nature of the fluid on the temperature dependence of contact angle is also
      discussed. 

PMID- 25381537
TI  - Thermal noise in confined fluids.
AB  - In this work, we discuss a combined memory function equation (MFE) and
      generalized Langevin equation (GLE) approach (referred to as MFE/GLE formulation)
      to characterize thermal noise in confined fluids. Our study reveals that for
      fluids confined inside nanoscale geometries, the correlation time and the time
      decay of the autocorrelation function of the thermal noise are not significantly
      different across the confinement. We show that it is the strong cross-correlation
      of the mean force with the molecular velocity that gives rise to the spatial
      anisotropy in the velocity-autocorrelation function of the confined fluids.
      Further, we use the MFE/GLE formulation to extract the thermal force a fluid
      molecule experiences in a MD simulation. Noise extraction from MD simulation
      suggests that the frequency distribution of the thermal force is non-Gaussian.
      Also, the frequency distribution of the thermal force near the confining surface
      is found to be different in the direction parallel and perpendicular to the
      confinement. We also use the formulation to compute the noise correlation time of
      water confined inside a (6,6) carbon-nanotube (CNT). It is observed that inside
      the (6,6) CNT, in which water arranges itself in a highly concerted single-file
      arrangement, the correlation time of thermal noise is about an order of magnitude
      higher than that of bulk water. 

PMID- 25381538
TI  - In situ synchrotron radiation photoelectron spectroscopy study of the oxidation
      of the Ge(100)-2 * 1 surface by supersonic molecular oxygen beams.
AB  - In situ synchrotron radiation photoelectron spectroscopy was performed during the
      oxidation of the Ge(100)-2 * 1 surface induced by a molecular oxygen beam with
      various incident energies up to 2.2 eV from the initial to saturation coverage of
      surface oxides. The saturation coverage of oxygen on the clean Ge(100) surface
      was much lower than one monolayer and the oxidation state of Ge was +2 at most.
      This indicates that the Ge(100) surface is so inert toward oxidation that
      complete oxidation cannot be achieved with only pure oxygen (O2) gas, which is in
      strong contrast to Si surfaces. Two types of dissociative adsorption, trapping
      mediated and direct dissociation, were confirmed by oxygen uptake measurements
      depending on the incident energy of O2. The direct adsorption process can be
      activated by increasing the translational energy, resulting in an increased
      population of Ge(2+) and a higher final oxygen coverage. We demonstrated that
      hyperthermal O2 beams remarkably promote the room-temperature oxidation with
      novel atomic configurations of oxides at the Ge(100) surface. Our findings will
      contribute to the fundamental understanding of oxygen adsorption processes at 300
      K from the initial stages to saturated oxidation. 

PMID- 25381539
TI  - Investigation of the influence of coadsorbent dye upon the interfacial structure
      of dye-sensitized solar cells.
AB  - The interface between Ru(tcterpy)(NCS)3TBA2 [black dye (BD); tcterpy = 4,4',4"
      tricarboxy-2,2':6',2"-terpyridine, NCS = thiocyanato, TBA = tetrabutylammonium
      cation] and nanocrystalline TiO2, as found in dye-sensitized solar cells, is
      investigated by soft-X-ray synchrotron radiation and compared with the adsorption
      structure of cis-Ru(Hdcbpy)2(NCS)2TBA2 (N719; dcbpy = 4,4'-dicarboxy-2,2'
      bipyridine) on TiO2 to elucidate the relationship between the adsorption mode of
      BD and the photocurrent with and without coadsorbed indoline dye D131. The depth
      profile is characterized with X-ray photoelectron spectroscopy and S K-edge X-ray
      absorption fine structure using synchrotron radiation. Both datasets indicate
      that one of the isothiocyanate groups of BD interacts with TiO2 via its S atom
      when the dye is adsorbed from a single-component solution. In contrast, the
      interaction is slightly suppressed when D131 is coadsorbed, indicated by the fact
      that the presence of D131 changes the adsorption mode of BD. Based upon these
      results, the number of BD dye molecules interacting with the substrate is shown
      to decrease by 10% when D131 is coadsorbed, and the dissociation is shown to be
      related to the short-circuit photocurrent in the 600-800 nm region. The design of
      a procedure to promote the preferential adsorption of D131 therefore leads to an
      improvement of the short-circuit current and conversion efficiency.

PMID- 25381540
TI  - Microscopic properties of lithium, sodium, and magnesium battery anode materials
      related to possible dendrite growth.
AB  - Lithium and magnesium exhibit rather different properties as battery anode
      materials with respect to the phenomenon of dendrite formation which can lead to
      short-circuits in batteries. Diffusion processes are the key to understanding
      structure forming processes on surfaces. Therefore, we have determined adsorption
      energies and barriers for the self-diffusion on Li and Mg using periodic density
      functional theory calculations and contrasted the results to Na which is also
      regarded as a promising electrode material in batteries. According to our
      calculations, magnesium exhibits a tendency towards the growth of smooth surfaces
      as it exhibits lower diffusion barriers than lithium and sodium, and as an hcp
      metal it favors higher-coordinated configurations in contrast to the bcc metals
      Li and Na. These characteristic differences are expected to contribute to the
      unequal tendencies of these metals with respect to dendrite growth. 

PMID- 25381541
TI  - Buckling transition in long alpha-helices.
AB  - The treatment of bending and buckling of stiff biopolymer filaments by the
      popular worm-like chain model does not provide adequate understanding of these
      processes at the microscopic level. Thus, we have used the atomistic molecular
      dynamic simulations and the Amber03 force field to examine the compression
      buckling of alpha-helix (AH) filaments at room temperature. It was found that the
      buckling instability occurs in AHs at the critical force f(c) in the range of
      tens of pN depending on the AH length. The decrease of the force f(c) with the
      contour length follows the prediction of the classic thin rod theory. At the
      force f(c) the helical filament undergoes the swift and irreversible transition
      from the smoothly bent structure to the buckled one. A sharp kink in the AH
      contour arises at the transition, accompanied by the disruption of the hydrogen
      bonds in its vicinity. The kink defect brings in an effective softening of the AH
      molecule at buckling. Nonbonded interactions between helical branches drive the
      rearrangement of a kinked AH into the ultimate buckled structure of a compact
      helical hairpin described earlier in the literature.

PMID- 25381543
TI  - Nonequilibrium thermodynamics of dilute polymer solutions in flow.
AB  - Modern materials processing applications and technologies often occur far from
      equilibrium. To this end, the processing of complex materials such as polymer
      melts and nanocomposites generally occurs under strong deformations and flows,
      conditions under which equilibrium thermodynamics does not apply. As a result,
      the ability to determine the nonequilibrium thermodynamic properties of polymeric
      materials from measurable quantities such as heat and work is a major challenge
      in the field. Here, we use work relations to show that nonequilibrium
      thermodynamic quantities such as free energy and entropy can be determined for
      dilute polymer solutions in flow. In this way, we determine the thermodynamic
      properties of DNA molecules in strong flows using a combination of simulations,
      kinetic theory, and single molecule experiments. We show that it is possible to
      calculate polymer relaxation timescales purely from polymer stretching dynamics
      in flow. We further observe a thermodynamic equivalence between nonequilibrium
      and equilibrium steady-states for polymeric systems. In this way, our results
      provide an improved understanding of the energetics of flowing polymer solutions.

PMID- 25381544
TI  - Geometry of flexible filament cohesion: better contact through twist?
AB  - Cohesive interactions between filamentous molecules have broad implications for a
      range of biological and synthetic materials. While long-standing theoretical
      approaches have addressed the problem of inter-filament forces from the limit of
      infinitely rigid rods, the ability of flexible filaments to deform intra-filament
      shape in response to changes in inter-filament geometry has a profound affect on
      the nature of cohesive interactions. In this paper, we study two theoretical
      models of inter-filament cohesion in the opposite limit, in which filaments are
      sufficiently flexible to maintain cohesive contact along their contours, and
      address, in particular, the role played by helical-interfilament geometry in
      defining interactions. Specifically, we study models of featureless, tubular
      filaments interacting via: (1) pair-wise Lennard-Jones (LJ) interactions between
      surface elements and (2) depletion-induced filament binding stabilized by
      electrostatic surface repulsion. Analysis of these models reveals a universal
      preference for cohesive filament interactions for non-zero helical skew, and
      further, that in the asymptotic limit of vanishing interaction range relative to
      filament diameter, the skew-dependence of cohesion approaches a geometrically
      defined limit described purely by the close-packing geometry of twisted tubular
      filaments. We further analyze non-universal features of the skew-dependence of
      cohesion at small-twist for both potentials, and argue that in the LJ model the
      pair-wise surface attraction generically destabilizes parallel filaments, while
      in the second model, pair-wise electrostatic repulsion in combination with non
      pairwise additivity of depletion leads to a meta-stable parallel state. 

PMID- 25381545
TI  - Dynamics of intermittent force fluctuations in vesicular nanotubulation.
AB  - Irregular force fluctuations are seen in most nanotubulation experiments. The
      dynamics behind their presence has, however, been neither commented upon nor
      modeled. A simple estimate of the mean energy dissipated in force drops turns out
      to be several times the thermal energy. This coupled with the rate dependent
      nature of the deformation reported in several experiments point to a dynamical
      origin of the serrations. We simplify the whole process of tether formation
      through a three-stage model of successive deformations of sphere to ellipsoid,
      neck-formation, and tubule birth and extension. Based on this, we envisage a rate
      softening frictional force at the neck that must be overcome before a nanotube
      can be pulled out. Our minimal model includes elastic and visco-elastic
      deformation of the vesicle, and has built-in dependence on pull velocity, vesicle
      radius, and other material parameters, enabling us to capture various kinds of
      serrated force-extension curves for different parameter choices. Serrations are
      predicted in the nanotubulation region. Other features of force-extension plots
      reported in the literature such as a plateauing serrated region beyond a force
      drop, serrated flow region with a small positive slope, an increase in the
      elastic threshold with pull velocity, force-extension curves for vesicles with
      larger radius lying lower than those for smaller radius, are all also predicted
      by the model. A toy model is introduced to demonstrate that the role of the
      friction law is limited to inducing stick-slip oscillations in the force, and all
      other qualitative and quantitative features emerging from the model can only be
      attributed to other physical mechanisms included in the deformation dynamics of
      the vesicle. 

PMID- 25381542
TI  - Free-energy calculations for semi-flexible macromolecules: applications to DNA
      knotting and looping.
AB  - We present a method to obtain numerically accurate values of configurational free
      energies of semiflexible macromolecular systems, based on the technique of
      thermodynamic integration combined with normal-mode analysis of a reference
      system subject to harmonic constraints. Compared with previous free-energy
      calculations that depend on a reference state, our approach introduces two
      innovations, namely, the use of internal coordinates to constrain the reference
      states and the ability to freely select these reference states. As a consequence,
      it is possible to explore systems that undergo substantially larger fluctuations
      than those considered in previous calculations, including semiflexible
      biopolymers having arbitrary ratios of contour length L to persistence length P.
      To validate the method, high accuracy is demonstrated for free energies of prime
      DNA knots with L/P = 20 and L/P = 40, corresponding to DNA lengths of 3000 and
      6000 base pairs, respectively. We then apply the method to study the free-energy
      landscape for a model of a synaptic nucleoprotein complex containing a pair of
      looped domains, revealing a bifurcation in the location of optimal synapse
      (crossover) sites. This transition is relevant to target-site selection by DNA
      binding proteins that occupy multiple DNA sites separated by large linear
      distances along the genome, a problem that arises naturally in gene regulation,
      DNA recombination, and the action of type-II topoisomerases. 

PMID- 25381546
TI  - Monte Carlo simulation and equation of state for flexible charged hard-sphere
      chain fluids: polyampholyte and polyelectrolyte solutions.
AB  - The thermodynamic modeling of flexible charged hard-sphere chains representing
      polyampholyte or polyelectrolyte molecules in solution is considered. The excess
      Helmholtz energy and osmotic coefficients of solutions containing short
      polyampholyte and the osmotic coefficients of solutions containing short
      polyelectrolytes are determined by performing canonical and isobaric-isothermal
      Monte Carlo simulations. A new equation of state based on the thermodynamic
      perturbation theory is also proposed for flexible charged hard-sphere chains. For
      the modeling of such chains, the use of solely the structure information of
      monomer fluid for calculating the chain contribution is found to be insufficient
      and more detailed structure information must therefore be considered. Two
      approaches, i.e., the dimer and dimer-monomer approaches, are explored to obtain
      the contribution of the chain formation to the Helmholtz energy. By comparing
      with the simulation results, the equation of state with either the dimer or dimer
      monomer approach accurately predicts the excess Helmholtz energy and osmotic
      coefficients of polyampholyte and polyelectrolyte solutions except at very low
      density. It also well captures the effect of temperature on the thermodynamic
      properties of these solutions. 

PMID- 25381548
TI  - The behaviour of basic autocatalytic signalling modules in isolation and embedded
      in networks.
AB  - In this paper, we examine the behaviour of basic autocatalytic feedback modules
      involving a species catalyzing its own production, either directly or indirectly.
      We first perform a systematic study of the autocatalytic feedback module in
      isolation, examining the effect of different factors, showing how this module is
      capable of exhibiting monostable threshold and bistable switch-like behaviour. We
      then study the behaviour of this module embedded in different kinds of basic
      networks including (essentially) irreversible cycles, open and closed reversible
      chains, and networks with additional feedback. We study the behaviour of the
      networks deterministically and also stochastically, using simulations, analytical
      work, and bifurcation analysis. We find that (i) there are significant
      differences between the behaviour of this module in isolation and in a network:
      thresholds may be altered or destroyed and bistability may be destroyed or even
      induced, even when the ambient network is simple. The global characteristics and
      topology of this network and the position of the module in the ambient network
      can play important and unexpected roles. (ii) There can be important differences
      between the deterministic and stochastic dynamics of the module embedded in
      networks, which may be accentuated by the ambient network. This provides new
      insights into the functioning of such enzymatic modules individually and as part
      of networks, with relevance to other enzymatic signalling modules as well. 

PMID- 25381547
TI  - Stability of Iowa mutant and wild type Abeta-peptide aggregates.
AB  - Recent experiments indicate a connection between the structure of amyloid
      aggregates and their cytotoxicity as related to neurodegenerative diseases. Of
      particular interest is the Iowa Mutant, which causes early-onset of Alzheimer's
      disease. While wild-type Amyloid beta-peptides form only parallel beta-sheet
      aggregates, the mutant also forms meta-stable antiparallel beta sheets. Since
      these structural variations may cause the difference in the pathological effects
      of the two Abeta-peptides, we have studied in silico the relative stability of
      the wild type and Iowa mutant in both parallel and antiparallel forms. We compare
      regular molecular dynamics simulations with such where the viscosity of the
      samples is reduced, which, we show, leads to higher sampling efficiency. By
      analyzing and comparing these four sets of all-atom molecular dynamics
      simulations, we probe the role of the various factors that could lead to the
      structural differences. Our analysis indicates that the parallel forms of both
      wild type and Iowa mutant aggregates are stable, while the antiparallel
      aggregates are meta-stable for the Iowa mutant and not stable for the wild type.
      The differences result from the direct alignment of hydrophobic interactions in
      the in-register parallel oligomers, making them more stable than the antiparallel
      aggregates. The slightly higher thermodynamic stability of the Iowa mutant fibril
      like oligomers in its parallel organization over that in antiparallel form is
      supported by previous experimental measurements showing slow inter-conversion of
      antiparallel aggregates into parallel ones. Knowledge of the mechanism that
      selects between parallel and antiparallel conformations and determines their
      relative stability may open new avenues for the development of therapies
      targeting familial forms of early-onset Alzheimer's disease. 

PMID- 25381549
TI  - Aggregation and network formation in self-assembly of protein (H3.1) by a coarse
      grained Monte Carlo simulation.
AB  - Multi-scale aggregation to network formation of interacting proteins (H3.1) are
      examined by a knowledge-based coarse-grained Monte Carlo simulation as a function
      of temperature and the number of protein chains, i.e., the concentration of the
      protein. Self-assembly of corresponding homo-polymers of constitutive residues
      (Cys, Thr, and Glu) with extreme residue-residue interactions, i.e., attractive
      (Cys-Cys), neutral (Thr-Thr), and repulsive (Glu-Glu), are also studied for
      comparison with the native protein. Visual inspections show contrast and
      similarity in morphological evolutions of protein assembly, aggregation of small
      aggregates to a ramified network from low to high temperature with the
      aggregation of a Cys-polymer, and an entangled network of Glu and Thr polymers.
      Variations in mobility profiles of residues with the concentration of the protein
      suggest that the segmental characteristic of proteins is altered considerably by
      the self-assembly from that in its isolated state. The global motion of proteins
      and Cys polymer chains is enhanced by their interacting network at the low
      temperature where isolated chains remain quasi-static. Transition from globular
      to random coil transition, evidenced by the sharp variation in the radius of
      gyration, of an isolated protein is smeared due to self-assembly of interacting
      networks of many proteins. Scaling of the structure factor S(q) with the wave
      vector q provides estimates of effective dimension D of the mass distribution at
      multiple length scales in self-assembly. Crossover from solid aggregates (D ~ 3)
      at low temperature to a ramified fibrous network (D ~ 2) at high temperature is
      observed for the protein H3.1 and Cys polymers in contrast to little changes in
      mass distribution (D ~ 1.6) of fibrous Glu- and Thr-chain configurations. 

PMID- 25381550
TI  - Emerging surgical pathways of thoracotomy.
AB  - Thoracic incisions are the portals of choice for accessing thoracic organs. There
      are instances, however, that more than one incision are required at the same or a
      later stage, in order to access other, thoracic or extrathoracic, organs for more
      complicated procedures. Then again, a single thoracic incision may offer more
      than adequate access to extrathoracic organs and in selected cases becomes
      valuable surgical approach to organs of the upper abdomen or the contralateral
      hemithorax. The experience with this technique is discussed. 

PMID- 25381551
TI  - Antioxidant activity characterization, phytochemical screening, and proximate
      analysis of Cermela Hutan (Phyllanthus gomphocarpus Hook. F) roots and leaves.
AB  - BACKGROUND: Roots and leaves of the Cermela Hutan (Phyllanthus gomphocarpus Hook.
      F) plant were studied to determine antioxidant activity, phytochemical compounds,
      proportion of carbohydrate, crude protein, moisture, ash, fat, total phenolic
      content (TPC), and total flavonoid content (TFC). MATERIAL/METHODS: Ten percent
      (10%) aqueous extract from both Phyllanthus gomphocarpus roots (PGR) and leaves
      (PGL) were used in this study. Antioxidant activity characterization by TPC, TFC,
      Ferric Reducing Antioxidant Power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      scavenging activity, and phytochemical screening, as well as proximate analysis
      from both extracts were analyzed in this study. RESULTS: Phyllanthus gomphocarpus
      roots (PGR) and leaves (PGL) tested positive for flavonoid, saponin, tannins, and
      terpenoids, but PGR showed negative result for anthraquinones. In average weight
      of 100.0 g dry sample, the carbohydrates, protein, moisture, ash, fat, and energy
      content in PGR and PGL were 80.9%, 5.5%, 7.8%, 3.4%, 2.4%, and 367 Kcal/100g, and
      66.5%, 14.8%, 10.7%, 6.5%, 1.5%, and 399 Kcal/100 g, respectively. Antioxidant
      assessments using FRAP and DPPH assay showed that PGL extracts possessed higher
      antioxidant capacity by reducing the ferric ion-TPTZ complex by 0.14 mg/ml +/
      0.0018 and higher scavenging activity, 83.83% +/-0.54 as compared to PGR, 0.07
      mg/ml +/-0.0035 for FRAP and 62.87% +/-1.33 for DPPH, respectively. The total
      phenolics content was significantly higher in PGL (208.77 mg GAE/g +/-3.79) as
      compared to PGR (27.53 mg GAE/g +/-0.42). However, there was no significant
      different in the total flavonoid contents for PGR (34.8 mg QE/g +/-3.12) and PGL
      (32.43 mg QE/g +/-3.92). CONCLUSIONS: Further investigations are suggested to
      isolate and characterize the other active constituents from this plant in
      combatting diseases.

PMID- 25381552
TI  - Impact of T-RFLP data analysis choices on assessments of microbial community
      structure and dynamics.
AB  - BACKGROUND: Terminal restriction fragment length polymorphism (T-RFLP) analysis
      is a common DNA-fingerprinting technique used for comparisons of complex
      microbial communities. Although the technique is well established there is no
      consensus on how to treat T-RFLP data to achieve the highest possible accuracy
      and reproducibility. This study focused on two critical steps in the T-RFLP data
      treatment: the alignment of the terminal restriction fragments (T-RFs), which
      enables comparisons of samples, and the normalization of T-RF profiles, which
      adjusts for differences in signal strength, total fluorescence, between samples.
      RESULTS: Variations in the estimation of T-RF sizes were observed and these
      variations were found to affect the alignment of the T-RFs. A novel method was
      developed which improved the alignment by adjusting for systematic shifts in the
      T-RF size estimations between the T-RF profiles. Differences in total
      fluorescence were shown to be caused by differences in sample concentration and
      by the gel loading. Five normalization methods were evaluated and the total
      fluorescence normalization procedure based on peak height data was found to
      increase the similarity between replicate profiles the most. A high peak
      detection threshold, alignment correction, normalization and the use of consensus
      profiles instead of single profiles increased the similarity of replicate T-RF
      profiles, i.e. lead to an increased reproducibility. The impact of different
      treatment methods on the outcome of subsequent analyses of T-RFLP data was
      evaluated using a dataset from a longitudinal study of the bacterial community in
      an activated sludge wastewater treatment plant. Whether the alignment was
      corrected or not and if and how the T-RF profiles were normalized had a
      substantial impact on ordination analyses, assessments of bacterial dynamics and
      analyses of correlations with environmental parameters. CONCLUSIONS: A novel
      method for the evaluation and correction of the alignment of T-RF profiles was
      shown to reduce the uncertainty and ambiguity in alignments of T-RF profiles.
      Large differences in the outcome of assessments of bacterial community structure
      and dynamics were observed between different alignment and normalization methods.
      The results of this study can therefore be of value when considering what methods
      to use in the analysis of T-RFLP data.

PMID- 25381553
TI  - The home environment and childhood obesity in low-income households: indirect
      effects via sleep duration and screen time.
AB  - BACKGROUND: Childhood obesity disproportionally affects children from low-income
      households. With the aim of informing interventions, this study examined pathways
      through which the physical and social home environment may promote childhood
      overweight/obesity in low-income households. METHODS: Data on health behaviors
      and the home environment were collected at home visits in low-income, urban
      households with either only normal weight (n = 48) or predominantly
      overweight/obese (n = 55) children aged 6-13 years. Research staff conducted
      comprehensive, in-person audits of the foods, media, and sports equipment in each
      household. Anthropometric measurements were collected, and children's physical
      activity was assessed through accelerometry. Caregivers and children jointly
      reported on child sleep duration, screen time, and dietary intake of foods
      previously implicated in childhood obesity risk. Path analysis was used to test
      direct and indirect associations between the home environment and child weight
      status via the health behaviors assessed. RESULTS: Sleep duration was the only
      health behavior associated with child weight status (OR = 0.45, 95% CI: 0.27,
      0.77), with normal weight children sleeping 33.3 minutes/day longer on average
      than overweight/obese children. The best-fitting path model explained 26% of
      variance in child weight status, and included paths linking chaos in the home
      environment, lower caregiver screen time monitoring, inconsistent implementation
      of bedtime routines, and the presence of a television in children's bedrooms to
      childhood overweight/obesity through effects on screen time and sleep duration.
      CONCLUSIONS: This study adds to the existing literature by identifying aspects of
      the home environment that influence childhood weight status via indirect effects
      on screen time and sleep duration in children from low-income households.
      Pediatric weight management interventions for low-income households may be
      improved by targeting aspects of the physical and social home environment
      associated with sleep.

PMID- 25381554
TI  - Analysis of the CYP2C19 genetic polymorphism in Han and Uyghur patients with
      cardiovascular and cerebrovascular diseases in the Kashi area of Xinjiang.
AB  - BACKGROUND: The aim of this study was to analyze the CYP2C19 genetic polymorphism
      among Han and Uyghur patients with cardiovascular and cerebrovascular diseases in
      the Kashi area of Xinjiang. MATERIAL/METHODS: We enrolled 1020 patients with
      cardiovascular and cerebrovascular diseases, including 220 Han subjects and 800
      Uyghur subjects. We used the gene chip method to detect polymorphisms in CYP2C19.
      The allele frequencies of CYP2C19 and the metabolic phenotype frequencies were
      then compared between the 2 ethnic groups. RESULTS: The frequency of CYP2C19 *1
      was 0.6454 in Han subjects and 0.7869 in Uyghur subjects, and the difference was
      statistically significant (P<0.05). The frequency of CYP2C19 *2 was 0.3273 in Han
      subjects and 0.1837 in Uyghur subjects (P<0.05). The frequency of the homozygous
      extensive metabolizer phenotype was 42.72% and 62.13% in Han and Uyghur subjects,
      respectively (P<0.01). The frequency of the heterozygous extensive metabolizer
      phenotype was 43.64% and 33.13% in Han and Uyghur subjects, respectively
      (P<0.01). The frequency of poor metabolizers in Han and Uyghur subjects was
      13.64% and 4.76%, respectively (P<0.01). CONCLUSIONS: Among patients with
      cardiovascular and cerebrovascular diseases located in the Kashgar Prefecture of
      Xinjiang, there is a differential distribution of CYP2C19 genotypes between the
      Han and Uyghur populations. Uyghur patients showed higher frequencies of
      extensive metabolizer genotypes than Han patients, while Han patients showed
      higher frequencies of poor metabolizer genotypes than Uyghur patients.

PMID- 25381555
TI  - Deletion of the gene encoding G0/G 1 switch protein 2 (G0s2) alleviates high-fat
      diet-induced weight gain and insulin resistance, and promotes browning of white
      adipose tissue in mice.
AB  - AIMS/HYPOTHESIS: Obesity is a global epidemic resulting from increased energy
      intake, which alters energy homeostasis and results in an imbalance in fat
      storage and breakdown. G0/G1 switch gene 2 (G0s2) has been recently characterised
      in vitro as an inhibitor of adipose triglyceride lipase (ATGL), the rate-limiting
      step in fat catabolism. In the current study we aim to functionally characterise
      G0s2 within the physiological context of a mouse model. METHODS: We generated a
      mouse model in which G0s2 was deleted. The homozygous G0s2 knockout (G0s2 (-/-))
      mice were studied over a period of 22 weeks. Metabolic variables were measured
      including body weight and body composition, food intake, glucose and insulin
      tolerance tests, energy metabolism and thermogenesis. RESULTS: We report that
      G0s2 inhibits ATGL and regulates lipolysis and energy metabolism in vivo. G0s2 (
      /-) mice are lean, resistant to weight gain induced by a high-fat diet and are
      glucose tolerant and insulin sensitive. The white adipose tissue of G0s2 (-/-)
      mice has enhanced lipase activity and adipocytes showed enhanced stimulated
      lipolysis. Energy metabolism in the G0s2 (-/-) mice is shifted towards enhanced
      lipid metabolism and increased thermogenesis. G0s2 (-/-) mice showed enhanced
      cold tolerance and increased expression of thermoregulatory and oxidation genes
      within white adipose tissue, suggesting enhanced 'browning' of the white adipose
      tissue. CONCLUSIONS/INTERPRETATION: Our data show that G0s2 is a physiological
      regulator of adiposity and energy metabolism and is a potential target in the
      treatment of obesity and insulin resistance.

PMID- 25381557
TI  - Respiratory infections in travelers returning from the tropics.
AB  - Respiratory tract infections (RTIs), beside diarrheas, skin lesions, and fevers
      of unknown origin, are one of the most common health problems acquired by
      travelers going to tropical and subtropical countries. Visitors to African,
      Asian, or South American destinations, typically characterized by harsh
      environmental conditions and poor sanitation standards, are at risk of exposure
      to a large number of pathogens causing infectious diseases. The infections are
      transmitted from contaminated food and water, through the air, direct contact, or
      by insects. The main modes of RTIs transmission include droplet infection and
      direct contact. The clinical spectrum of RTIs in travelers is broad, from upper
      respiratory tract infections, pharyngitis, bronchitis, pneumonia, to influenza
      like illness. The spectrum of microbial agents causing respiratory infections
      include numerous viruses and bacteria, rarely fungi, and parasites. Most
      travelers complain of mild infections, only a small minority seek medical
      assistance and report to health care facilities. Because of the risk of importing
      pathogens into Europe or North America and transferring them onto the local
      population, it is important to present the scale of the problem in relation to
      rapid development of tourism industry and an increasing number of
      intercontinental journeys. The aim of the study was to discuss the occurrence of
      travel-related respiratory infections among representatives of temperate climate
      traveling to and returning from the tropics. 

PMID- 25381556
TI  - Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in
      rat pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: Insulin is a key metabolic regulator in health and diabetes. In
      pancreatic beta cells, insulin release is regulated by the major second
      messengers Ca(2+) and cAMP: exocytosis is triggered by Ca(2+) and mediated by the
      cAMP/protein kinase A (PKA) signalling pathway. However, the causal link between
      these two processes in primary beta cells remains undefined. METHODS: Time
      resolved confocal imaging of fluorescence resonance energy transfer signals was
      performed to visualise PKA activity, and combined membrane capacitance recordings
      were used to monitor insulin secretion from patch-clamped rat beta cells.
      RESULTS: Membrane depolarisation-induced Ca(2+) influx caused an increase in
      cytosolic PKA activity via activating a Ca(2+)-sensitive adenylyl cyclase 8
      (ADCY8) subpool. Glucose stimulation triggered coupled Ca(2+) oscillations and
      PKA activation. ADCY8 knockdown significantly reduced the level of depolarisation
      evoked PKA activation and impaired replenishment of the readily releasable
      vesicle pool. Pharmacological inhibition of PKA by two inhibitors reduced
      depolarisation-induced PKA activation to a similar extent and reduced the
      capacity for sustained vesicle exocytosis and insulin release.
      CONCLUSIONS/INTERPRETATION: Our findings suggest that depolarisation-induced
      Ca(2+) influx plays dual roles in regulating exocytosis in rat pancreatic beta
      cells by triggering vesicle fusion and replenishing the vesicle pool to support
      sustained insulin release. Therefore, Ca(2+) influx may be important for glucose
      stimulated insulin secretion.

PMID- 25381558
TI  - Diffusion limitations of the lung - comparison of different measurement methods.
AB  - Pulmonary fibrosis leads to a decrease of oxygen diffusion, in particular during
      exercise. Bronchial obstruction also could decrease the partial pressure of
      oxygen (P(a)O(2)). In this study we investigated the validity of blood gas
      content, especially P(a)O(2) and P(a)O(2) affected by hyperventilation
      (P(a)O(2corr)) and alveolo-arterial oxygen gradient (P(A-a)O(2)) in comparison
      with the CO diffusion capacity (DLCO) in different lung diseases. A total of 250
      subjects were studied (52.3 +/- 12.5 year; F/M 40/210), among which there were
      162 subjects with different lung disorders and 88 healthy controls. Pearson's
      correlation coefficients (r) of DLCO with P(a)O(2), P(a)O(2corr), and PA-aO(2)
      were analyzed in each group. The results show that the diagnostic power of P(A
      a)O(2) against P(a)O(2corr) was equivalent, especially during exercise (r = -0.89
      and -0.92, respectively). DLCO showed only weak correlations with P(a)O(2corr)
      and P(A-a)O(2) (r = 0.17 and -0.19, respectively). In conclusion, DLCO shows a
      better match with blood gas content during exercise than at rest during which it
      is routinely tested. Thus, the exercise test is advisable. The P(A-a)O(2) takes
      into account the level of ventilation, which makes it correlate better with DLCO
      rather than with blood gas content. The most significant problems in clinical
      evaluation of blood gas parameters during exercise are the insufficiently defined
      limits of normal-to-pathological range.

PMID- 25381559
TI  - The influence of particulate matter on respiratory morbidity and mortality in
      children and infants.
AB  - Air pollution is the most important environmental health risk leading to
      premature mortality, respiratory and other health problems. The aim of this study
      was to quantify its impact on infants and children in Warsaw (Poland), following
      the principles of Health Impact Assessment method. Particulate matter (PM(2.5)
      and PM(10)) was considered as the indicator of air pollution. Exposure-response
      functions between air pollution and health impacts were employed based on the
      literature. According to the calculations, around 5,201 asthma symptoms and 234
      hospital respiratory admissions were caused annually due to air pollution.
      Hospitalizations due to cardiovascular problems related to air pollution amounted
      to 13. The mortality among infants and children is relatively low and occurs
      mostly in the postneonatal period. Nonetheless, approx. 5 mortality cases were
      assessed to be air pollution-attributable. The study demonstrates a significant
      impact of air pollution on infants and children, which is manifested primarily as
      a range of respiratory problems.

PMID- 25381562
TI  - Factors enhancing utilization of and adherence to prevention of mother-to-child
      transmission (PMTCT) service in an urban setting in Kenya.
AB  - Despite expansive scale-up of prevention of mother-to-child transmission (PMTCT)
      of HIV services in Kenya over the last decade, Kenya remains one of the countries
      contributing to high numbers of children living with HIV globally and is among
      the 22 PMTCT global plan priority countries. Using structured and in-depth
      interviews this study examined enabling factors that enhance utilization of and
      adherence to PMTCT services in an urban setting in Kenya. HIV-positive
      birthmothers (N = 55) whose infants were HIV-negative at the time of the study
      completed a structured interview and a subset (n = 15) participated in in-depth
      interviews. The majority of the mothers (98 %) delivered at a health facility and
      91 % exclusively breastfed. Further, 91 % attended clinic appointments regularly
      and 69.1 % strictly adhered to prescribed medication dosage and schedules.
      However, 18 % had not disclosed their HIV status to anybody, 27 % did not use
      condom during sex, 95 % did not participate in AIDS support groups and 53 % of
      their male partners were not involved in PMTCT. Four key themes facilitating
      PMTCT success emerged from the qualitative data: supportive counseling, striving
      for motherhood, assurance of confidentiality; and confirmation, affirmation and
      admiration. HIV/AIDS related stigma and gender imbalances create many missed
      opportunities for HIV-positive mothers to reach out for support from family and
      community, apply acquired knowledge and access more affordable care. To be
      successful, PMTCT programs should be aware of these factors and ensure that
      mothers are provided with culturally competent care. 

PMID- 25381561
TI  - Sexual orientation- and race-based discrimination and sexual HIV risk behavior
      among urban MSM.
AB  - Understanding what social factors are associated with risk of HIV acquisition and
      transmission among gay, bisexual and other men who have sex with men (MSM) is a
      critical public health goal. Experiencing discrimination may increase risk of HIV
      infection among MSM. This analysis assessed relations between experiences of
      sexual orientation- and race-based discrimination and sexual HIV risk behavior
      among MSM in New York City. 1,369 MSM completed a self-administered computerized
      assessment of past 3-month sexual behavior, experience of social discrimination
      and other covariates. Regression models assessed relations between recent
      experience of discrimination and sexual HIV risk behavior. Mean age was 32 years;
      32 % were white; 32 % Latino/Hispanic; 25 % African American/Black. Of MSM who
      self-reported HIV-positive or unknown status (377), 7 % (N = 27) reported having
      unprotected insertive anal intercourse with an HIV-negative or unknown status
      partner ("HIV transmission risk"). Of MSM who self-reported HIV-negative status
      (992), 11 % (110) reported unprotected receptive anal intercourse with an HIV
      positive or unknown status partner ("HIV acquisition risk"). HIV acquisition risk
      was positively associated with sexual orientation-based discrimination in home or
      social neighborhoods, but not race-based discrimination. We observed that sexual
      orientation-based discrimination was associated with sexual HIV risk behavior
      among urban-dwelling MSM. Addressing environmental sources of this form of
      discrimination, as well as the psychological distress that may result, should be
      prioritized in HIV prevention efforts. 

PMID- 25381560
TI  - Coronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: The incidence of cardiovascular disease (CVD) in rheumatoid arthritis
      (RA) is increased compared to the general population. Immune dysregulation and
      systemic inflammation are thought to be associated with this increased risk.
      Early diagnosis with immediate treatment and tight control of RA forms a central
      treatment paradigm. It remains unclear, however, whether using tumor necrosis
      factor inhibitors (TNFi) to achieve remission confer additional beneficial
      effects over standard therapy, especially on the development of CVD.
      METHODS/DESIGN: Coronary Artery Disease Evaluation in Rheumatoid Arthritis
      (CADERA) is a prospective cardiovascular imaging study that bolts onto an
      existing single-centre, randomized controlled trial, VEDERA (Very Early versus
      Delayed Etanercept in Rheumatoid Arthritis). VEDERA will recruit 120 patients
      with early, treatment-naive RA, randomized to TNFi therapy etanercept (ETN)
      combined with methotrexate (MTX), or therapy with MTX with or without additional
      synthetic disease modifying anti-rheumatic drugs with escalation to ETN following
      a 'treat-to-target' regimen. VEDERA patients will be recruited into CADERA and
      undergo cardiac magnetic resonance (CMR) assessment with; cine imaging,
      rest/stress adenosine perfusion, tissue-tagging, aortic distensibility, T1
      mapping and late gadolinium imaging. Primary objectives are to detect the
      prevalence and change of cardiovascular abnormalities by CMR between TNFi and
      standard therapy over a 12-month period. All patients will enter an inflammatory
      arthritis registry for long-term follow-up. DISCUSSION: CADERA is a multi
      parametric study describing cardiovascular abnormalities in early, treatment
      naive RA patients, with assessment of changes at one year between early
      biological therapy and conventional therapy. TRIALS REGISTRATION: This trial was
      registered with Current Controlled Trials (registration number: ISRCTN50167738)
      on 8 November 2013.

PMID- 25381563
TI  - Acceptability and feasibility of using established geosocial and sexual
      networking mobile applications to promote HIV and STD testing among men who have
      sex with men.
AB  - This study is the first published multi-app study, of which we are aware, to
      evaluate both the acceptability and feasibility of providing sexual health
      information and HIV/STD testing referrals via established geosocial and sexual
      networking apps for MSM. Data were collected using an online survey and through
      four apps (A4A Radar, Grindr, Jack'd, and Scruff). Two-thirds (64 %) found apps
      to be an acceptable source for sexual health information. MSM who found apps as
      acceptable were more likely non-white, not sure of their current HIV status, and
      have low HIV testing self-efficacy. One-quarter (26 %) of informational chats
      with the health educator resulted in users requesting and being referred to local
      HIV/STD testing sites. There were significant differences in the number and types
      of interactions across apps. Established apps designed for MSM may be both an
      acceptable and feasible platform to promote HIV/STD testing. Future research
      should evaluate interventions that leverage this technology.

PMID- 25381564
TI  - Multiple tumor marker protein chip detection system in diagnosis of pancreatic
      cancer.
AB  - BACKGROUND: The clinical stage of the disease at diagnosis often determines the
      prognosis and survival rate of a patient with pancreatic cancer. Early symptoms
      of pancreatic cancer are often not obvious on imaging (ultrasound, computed
      tomography (CT), and so on), and when patients present with weight loss, jaundice
      and abdominal pain and other symptoms, they are usually already in the advanced
      stages of pancreatic cancer. However, the examination of combined tumor markers
      might improve their sensitivity or specificity in aiding diagnosis. METHODS:
      Twelve tumor markers including AFP, CEA, NSE, CA125, CA15-3, CA242, CA19-9, PSA,
      f-PSA, FER, beta-HCG and HGH were measured by the protein biochip detection in
      serum in 235 pancreatic cancer patients, 230 benign pancreatic disease patients
      and 240 healthy people. RESULTS: Positive detection rates of tumor markers were:
      CA19-9 (49.3%), CA125 (45.1%), FER (44.2%), CA242 (42.5%), CEA (38.6%), CA15-3
      (36.7%), beta-HCG (29.6%), AFP (24.5%), NSE (18.2%), PSA (19.5%), f-PSA (9.4%)
      and HGH (8.7%) respectively. There was significant difference in CA19-9, NSE,
      CEA, CA242 and CA125 by multi-tumor marker protein biochip detection among
      patients with cancer, benign disease and healthy people (P<0.05). The positive
      rate of 5 tumor markers was 94.9%, and this was much higher than that of any
      single marker. CONCLUSION: The detection of CA19-9, NSE, CEA, CA242 and CA125 in
      the multi-tumor marker protein biochip system is helpful in the diagnosis of
      pancreatic cancer.

PMID- 25381566
TI  - Fast magic angle spinning NMR with heteronucleus detection for resonance
      assignments and structural characterization of fully protonated proteins.
AB  - Heteronucleus-detected dipolar based correlation spectroscopy is established for
      assignments of 1H, 13C, and 15N resonances and structural analysis in fully
      protonated proteins. We demonstrate that 13C detected 3D experiments are highly
      efficient and permit assignments of the majority of backbone resonances, as shown
      in an 89-residue dynein light chain 8, LC8 protein. With these experiments, we
      have resolved many ambiguities that were persistent in our previous studies using
      moderate MAS frequencies and lacking the 1H dimension. The availability of 1H
      isotropic chemical shifts measured with the heteronucleus-detected fast-MAS
      experiments presented here is essential for the accurate determination of the 1H
      CSA tensors, which provide very useful structural probe. Finally, our results
      indicate that 13C detection in fast-MAS HETCOR experiments may be advantageous
      compared with 1H detection as it yields datasets of significantly higher
      resolution in the 13C dimension than the 1H detected HETCOR versions.

PMID- 25381567
TI  - A 3D time-shared NOESY experiment designed to provide optimal resolution for
      accurate assignment of NMR distance restraints in large proteins.
AB  - Structure determination of proteins by solution NMR has become an established
      method, but challenges increase steeply with the size of proteins. Notably,
      spectral crowding and signal overlap impair the analysis of cross-peaks in NOESY
      spectra that provide distance restraints for structural models. An optimal
      spectral resolution can alleviate overlap but requires prohibitively long
      experimental time with existing methods. Here we present a time-shared 3D
      experiment optimized for large proteins that provides 15N and 13C dispersed NOESY
      spectra in a single measurement. NOESY correlations appear in the detected
      dimension and hence benefit from the highest resolution achievable of all
      dimensions without increase in experimental time. By design, this experiment is
      inherently optimal for non-uniform sampling acquisition when compared to current
      alternatives. Thus, 15N and 13C dispersed NOESY spectra with ultra-high
      resolution in all dimensions were acquired in parallel within about 4 days
      instead of 80 days for a 52 kDa monomeric protein at a concentration of 350 MUM.

PMID- 25381568
TI  - Vascularization of engineered cartilage constructs in a mouse model.
AB  - Tissue engineering of cartilage tissue offers a promising method for
      reconstructing ear, nose, larynx and trachea defects. However, a lack of
      sufficient nutrient supply to cartilage constructs limits this procedure. Only a
      few animal models exist to vascularize the seeded scaffolds. In this study,
      polycaprolactone (PCL)-based polyurethane scaffolds are seeded with 1 * 10(6)
      human cartilage cells and implanted in the right hind leg of a nude mouse using
      an arteriovenous flow-through vessel loop for angiogenesis for the first 3 weeks.
      Equally seeded scaffolds but without access to a vessel loop served as controls.
      After 3 weeks, a transposition of the vascularized scaffolds into the groin of
      the nude mouse was performed. Constructs (verum and controls) were explanted 1
      and 6 weeks after transposition. Constructs with implanted vessels were well
      vascularized. The amount of cells increased in vascularized constructs compared
      to the controls but at the same time noticeably less extracellular matrix was
      produced. This mouse model provides critical answers to important questions
      concerning the vascularization of engineered tissue, which offers a viable option
      for repairing defects, especially when the desired amount of autologous cartilage
      or other tissues is not available and the nutritive situation at the implantation
      site is poor.

PMID- 25381569
TI  - A novel aspect of the structure of the avian thymic medulla.
AB  - We provide evidence for the compartmentalization of the avian thymic medulla and
      identify the avian thymic dendritic cell. The thymic anlage develops from an
      epithelial cord of the branchial endoderm. Branches of the cord are separated by
      primary septae of neural crest origin. The dilation of the primary septae
      produces the keratin-negative area (KNA) of the thymic medulla and fills the gaps
      of the keratin-positive network (KPN). Morphometric analysis indicates that the
      KNA takes up about half of the volume of the thymic medulla, which has reticular
      connective tissue, like peripheral lymphoid organs. The KNA receives blood
      vessels and in addition to pericytes, the myoid cells of striated muscle
      structure occupy this area. The myoid cells are of branchial arch or prechordal
      plate origin providing indirect evidence for the neural crest origin of the KNA.
      The marginal epithelial cells of the KPN co-express keratin and vimentin
      intermediate filaments, which indicate their functional peculiarity. The basal
      lamina of the primary septum is discontinuous on the surface of the KPN providing
      histological evidence for the loss of the blood-thymus barrier in the medulla. In
      the center of the KNA, the dendritic cells lie in close association with blood
      vessels, whereas the B-cells accumulate along the KPN. The organization of the
      KPN and KNA increases the "surface" of the so-called cortico-medullary border,
      thereby contributing to the efficacy of central tolerance. 

PMID- 25381565
TI  - Current View on Osteogenic Differentiation Potential of Mesenchymal Stromal Cells
      Derived from Placental Tissues.
AB  - Mesenchymal stromal cells (MSC) isolated from human term placental tissues
      possess unique characteristics, including their peculiar immunomodulatory
      properties and their multilineage differentiation potential. The osteogenic
      differentiation capacity of placental MSC has been widely disputed, and continues
      to be an issue of debate. This review will briefly discuss the different MSC
      populations which can be obtained from different regions of human term placenta,
      along with their unique properties, focusing specifically on their osteogenic
      differentiation potential. We will present the strategies used to enhance
      osteogenic differentiation potential in vitro, such as through the selection of
      subpopulations more prone to differentiate, the modification of the components of
      osteo-inductive medium, and even mechanical stimulation. Accordingly, the
      applications of three-dimensional environments in vitro and in vivo, such as non
      synthetic, polymer-based, and ceramic scaffolds, will also be discussed, along
      with results obtained from pre-clinical studies of placental MSC for the
      regeneration of bone defects and treatment of bone-related diseases.

PMID- 25381570
TI  - Connexins and gap junctions in the inner ear--it's not just about K+ recycling.
AB  - Normal development, function and repair of the sensory epithelia in the inner ear
      are all dependent on gap junctional intercellular communication. Mutations in the
      connexin genes GJB2 and GJB6 (encoding CX26 and CX30) result in syndromic and non
      syndromic deafness via various mechanisms. Clinical vestibular defects, however,
      are harder to connect with connexin dysfunction. Cx26 and Cx30 proteins are
      widely expressed in the epithelial and connective tissues of the cochlea, where
      they may form homomeric or heteromeric gap junction channels in a cell-specific
      and spatiotemporally complex fashion. Despite the study of mutant channels and
      animal models for both recessive and dominant autosomal deafness, it is still
      unclear why gap junctions are essential for auditory function, and why Cx26 and
      Cx30 do not compensate for each other in vivo. Cx26 appears to be essential for
      normal development of the auditory sensory epithelium, but may be dispensable
      during normal hearing. Cx30 appears to be essential for normal repair following
      sensory cell loss. The specific modes of intercellular signalling mediated by
      inner ear gap junction channels remain undetermined, but they are hypothesised to
      play essential roles in the maintenance of ionic and metabolic homeostasis in the
      inner ear. Recent studies have highlighted involvement of gap junctions in the
      transfer of essential second messengers between the non-sensory cells, and have
      proposed roles for hemichannels in normal hearing. Here, we summarise the current
      knowledge about the molecular and functional properties of inner ear gap
      junctions, and about tissue pathologies associated with connexin mutations. 

PMID- 25381572
TI  - Isolation and characterization of oxalotrophic bacteria from tropical soils.
AB  - The oxalate-carbonate pathway (OCP) is a biogeochemical set of reactions that
      involves the conversion of atmospheric CO2 fixed by plants into biomass and,
      after the biological recycling of calcium oxalate by fungi and bacteria, into
      calcium carbonate in terrestrial environments. Oxalotrophic bacteria are a key
      element of this process because of their ability to oxidize calcium oxalate.
      However, the diversity and alternative carbon sources of oxalotrophs
      participating to this pathway are unknown. Therefore, the aim of this study was
      to characterize oxalotrophic bacteria in tropical OCP systems from Bolivia,
      India, and Cameroon. Ninety-five oxalotrophic strains were isolated and
      identified by sequencing of the 16S rRNA gene. Four genera corresponded to newly
      reported oxalotrophs (Afipia, Polaromonas, Humihabitans, and Psychrobacillus).
      Ten strains were selected to perform a more detailed characterization. Kinetic
      curves and microcalorimetry analyses showed that Variovorax soli C18 has the
      highest oxalate consumption rate with 0.240 uM h(-1). Moreover, Streptomyces
      achromogenes A9 displays the highest metabolic plasticity. This study highlights
      the phylogenetic and physiological diversity of oxalotrophic bacteria in tropical
      soils under the influence of the oxalate-carbonate pathway. 

PMID- 25381571
TI  - Inner ear development: building a spiral ganglion and an organ of Corti out of
      unspecified ectoderm.
AB  - The mammalian inner ear develops from a placodal thickening into a complex
      labyrinth of ducts with five sensory organs specialized to detect position and
      movement in space. The mammalian ear also develops a spiraled cochlear duct
      containing the auditory organ, the organ of Corti (OC), specialized to translate
      sound into hearing. Development of the OC from a uniform sheet of ectoderm
      requires unparalleled precision in the topological developmental engineering of
      four different general cell types, namely sensory neurons, hair cells, supporting
      cells, and general otic epithelium, into a mosaic of ten distinctly recognizable
      cell types in and around the OC, each with a unique distribution. Moreover, the
      OC receives unique innervation by ear-derived spiral ganglion afferents and
      brainstem-derived motor neurons as efferents and requires neural-crest-derived
      Schwann cells to form myelin and neural-crest-derived cells to induce the stria
      vascularis. This transformation of a sheet of cells into a complicated
      interdigitating set of cells necessitates the orchestrated expression of multiple
      transcription factors that enable the cellular transformation from ectoderm into
      neurosensory cells forming the spiral ganglion neurons (SGNs), while
      simultaneously transforming the flat epithelium into a tube, the cochlear duct,
      housing the OC. In addition to the cellular and conformational changes forming
      the cochlear duct with the OC, changes in the surrounding periotic mesenchyme
      form passageways for sound to stimulate the OC. We review molecular developmental
      data, generated predominantly in mice, in order to integrate the well-described
      expression changes of transcription factors and their actions, as revealed in
      mutants, in the formation of SGNs and OC in the correct position and orientation
      with suitable innervation. Understanding the molecular basis of these
      developmental changes leading to the formation of the mammalian OC and
      highlighting the gaps in our knowledge might guide in vivo attempts to regenerate
      this most complicated cellular mosaic of the mammalian body for the
      reconstitution of hearing in a rapidly growing population of aging people
      suffering from hearing loss. 

PMID- 25381573
TI  - Is Cytoplasmic PTEN a Specific Target for Neuronal Survival?
AB  - The differential sensitivity of neurons to phosphatase and tensin homolog's
      (PTEN) lipid and protein phosphatase actions pose difficulties in defining the
      exact neuronal phenotype generated by targeting PTEN in neuronal injury. PTEN's
      biology beyond its phosphatase functions are also emerging. Considering spatial
      dynamics of PTEN a decisive factor for its mode of action we propose selective
      targeting of its cytoplasmic fraction a better therapeutic approach in neuronal
      injury. 

PMID- 25381576
TI  - Problem-solving and learning in Carib grackles: individuals show a consistent
      speed-accuracy trade-off.
AB  - The generation and maintenance of within-population variation in cognitive
      abilities remain poorly understood. Recent theories propose that this variation
      might reflect the existence of consistent cognitive strategies distributed along
      a slow-fast continuum influenced by shyness. The slow-fast continuum might be
      reflected in the well-known speed-accuracy trade-off, where animals cannot
      simultaneously maximise the speed and the accuracy with which they perform a
      task. We test this idea on 49 wild-caught Carib grackles (Quiscalus lugubris), a
      tame opportunistic generalist Icterid bird in Barbados. Grackles that are fast at
      solving novel problems involving obstacle removal to reach visible food perform
      consistently over two different tasks, spend more time per trial attending to
      both tasks, and are those that show more shyness in a pretest. However, they are
      also the individuals that make more errors in a colour discrimination task
      requiring no new motor act. Our data reconcile some of the mixed positive and
      negative correlations reported in the comparative literature on cognitive tasks,
      suggesting that a speed-accuracy trade-off could lead to negative correlations
      between tasks favouring speed and tasks favouring accuracy, but still reveal
      consistent strategies based on stable individual differences. 

PMID- 25381575
TI  - ATF4: a Novel Potential Therapeutic Target for Alzheimer's Disease.
AB  - Activating transcription factor 4 (ATF4) belongs to the activating transcription
      factor family and its expression is increased upon the stimulation of a diverse
      array of microenvironmental stresses. ATF4 plays a major role in the development,
      metabolism, and memory formation. Alzheimer's disease (AD) is a prevalent
      neurodegenerative disease in aged population. The dominant pathological changes
      in AD brain, including the neurofibrillary tangles, consist of
      hyperphosphorylated tau protein, senile plaques composed of beta-amyloid
      proteins, loss of neurons in the whole brain, and dysfunction of synapses. The
      protein level of ATF4 is upregulated in both AD brain and AD mouse model,
      indicating its latent roles in the pathogenesis of this disease. In this paper,
      we reviewed the related literatures about the interaction of ATF4 with the
      different types of pathological changes in AD brain and pointed out some unsolved
      problems in this area. We also proposed that a fine regulation of ATF4 in
      separate neurons or brain regions might be benefit to the therapy of AD. 

PMID- 25381574
TI  - Inhibitory Effects of Bisphenol-A on Neural Stem Cells Proliferation and
      Differentiation in the Rat Brain Are Dependent on Wnt/beta-Catenin Pathway.
AB  - Neurogenesis, a process of generation of new neurons, occurs throughout the life
      in the hippocampus and sub-ventricular zone (SVZ). Bisphenol-A (BPA), an
      endocrine disrupter used as surface coating for packaged food cans, injures the
      developing and adult brain. However, the effects of BPA on neurogenesis and
      underlying cellular and molecular mechanism(s) are still unknown. Herein, we
      studied the effect(s) of prenatal and early postnatal exposure of low dose BPA on
      Wnt/beta-catenin signaling pathway that controls different steps of neurogenesis
      such as neural stem cell (NSC) proliferation and neuronal differentiation.
      Pregnant rats were treated with 4, 40, and 400 MUg BPA/kg body weight orally
      daily from gestational day 6 to postnatal day 21. Both in vivo and in vitro
      studies showed that BPA alters NSC proliferation and differentiation. BPA
      impaired NSC proliferation (5'-bromo-2'-deoxyuridine (BrdU(+)) and nestin(+)
      cells) and neuronal differentiation (BrdU/doublecortin(+) and BrdU/neuronal
      nuclei (NeuN(+)) cells) in the hippocampus and SVZ as compared to control. It
      significantly altered expression/protein levels of neurogenic genes and the Wnt
      pathway genes in the hippocampus. BPA reduced cellular beta-catenin and p-GSK
      3beta levels and decreased beta-catenin nuclear translocation, and cyclin-D1 and
      TCF/LEF promoter luciferase activity. Specific activation and blockage of the Wnt
      pathway suggested involvement of this pathway in BPA-mediated inhibition of
      neurogenesis. Further, blockage of GSK-3beta activity by SB415286 and GSK-3beta
      small interfering RNA (siRNA) attenuated BPA-induced downregulation of
      neurogenesis. Overall, these results suggest significant inhibitory effects of
      BPA on NSC proliferation and differentiation in the rat via the Wnt/beta-catenin
      signaling pathway.

PMID- 25381577
TI  - Evidence of in situ microbial activity and sulphidogenesis in perennially sub-0 
      degrees C and hypersaline sediments of a high Arctic permafrost spring.
AB  - The lost hammer (LH) spring perennially discharges subzero hypersaline reducing
      brines through thick layers of permafrost and is the only known terrestrial
      methane seep in frozen settings on Earth. The present study aimed to identify
      active microbial communities that populate the sediments of the spring outlet,
      and verify whether such communities vary seasonally and spatially. Microcosm
      experiments revealed that the biological reduction of sulfur compounds (SR) with
      hydrogen (e.g., sulfate reduction) was potentially carried out under combined
      hypersaline and subzero conditions, down to -20  degrees C, the coldest
      temperature ever recorded for SR. Pyrosequencing analyses of both 16S rRNA (i.e.,
      cDNA) and 16S rRNA genes (i.e., DNA) of sediments retrieved in late winter and
      summer indicated fairly stable bacterial and archaeal communities at the phylum
      level. Potentially active bacterial and archaeal communities were dominated by
      clades related to the T78 Chloroflexi group and Halobacteria species,
      respectively. The present study indicated that SR, hydrogenotrophy (possibly
      coupled to autotrophy), and short-chain alkane degradation (other than methane),
      most likely represent important, previously unaccounted for, metabolic processes
      carried out by LH microbial communities. Overall, the obtained findings provided
      additional evidence that the LH system hosts active communities of anaerobic,
      halophilic, and cryophilic microorganisms despite the extreme conditions in situ.

PMID- 25381578
TI  - The impact of multifocal intraocular lens in retinal imaging with optical
      coherence tomography.
AB  - Multifocal intraocular lenses (MF IOLs) have concentric optical zones with
      different dioptric power, enabling patients to have good visual acuity at
      multiple focal points. However, several optical limitations have been attributed
      to this particular design. The purpose of this study is to access the effect of
      MF IOLs design on the accuracy of retinal optical coherence tomography (OCT).
      Cross-sectional study conducted at the Refractive Surgery Department of Central
      Lisbon Hospital Center. Twenty-three eyes of 15 patients with a diffractive MF
      IOL and 27 eyes of 15 patients with an aspheric monofocal IOL were included in
      this study. All patients underwent OCT macular scans using Heidelberg
      Spectralis((r)). Macular thickness and volume values and image quality (Q factor)
      were compared between the two groups. There were no statistically significant
      differences between both groups regarding macular thickness or volume
      measurements. Retinal OCT image quality was significantly lower in the MF IOL
      group (p < 0.01). MF IOLs are associated with a significant decrease in OCT image
      quality. However, this fact does not seem to compromise the accuracy of spectral
      domain OCT retinal measurements.

PMID- 25381579
TI  - Whole-brain 320-detector row dynamic volume CT perfusion detected crossed
      cerebellar diaschisis after spontaneous intracerebral hemorrhage.
AB  - INTRODUCTION: The purpose of this study was to evaluate the value of 320-detector
      row CT used to detect crossed cerebellar diaschisis (CCD) in patients with
      unilateral supratentorial spontaneous intracerebral hemorrhage (SICH). METHODS:
      We investigated 62 of 156 patients with unilateral supratentorial SICH using 320
      detector row CT scanning. Regional cerebral blood flow (rCBF), cerebral blood
      volume (rCBV), mean transit time (rMTT), and time to peak (rTTP) levels were
      measured in different regions of interest (ROIs) that were manually outlined on
      computed tomography perfusion (CTP) for the cerebrum, including normal-appearing
      brain tissue that surrounded the perilesional low-density area (NA) and the
      perihematomal low-density area (PA) in all patients and the cerebellum
      (ipsilateral and contralateral) in CCD-positive patients. RESULTS: Of 62 cases, a
      total of 14 met the criteria for CCD due to cerebellar perfusion asymmetry on CTP
      maps. In the quantitative analysis, significant differences were found in the
      perfusion parameters between the contralateral and ipsilateral cerebellum in CCD
      positive cases. No significant differences were found between the CCD-positive
      group and the CCD-negative group according to the hematoma volume, NIHSS scores,
      and cerebral perfusion abnormality (each P > 0.05). The correlation analysis of
      the degree of NA, PA perfusion abnormality, and the degree of CCD severity showed
      negative and significant linear correlations (R, -0.66~-0.56; P < 0.05).
      CONCLUSION: 320-detector row CT is a robust and practicable method for the
      comprehensive primary imaging work-up of CCD in unilateral supratentorial SICH
      patients.

PMID- 25381580
TI  - Central skull base osteomyelitis: new insights and implications for diagnosis and
      treatment.
AB  - Central skull base osteomyelitis (SBO) is a life-threatening disease originating
      from ear and from sinonasal infections. The intention of this study was to
      evaluate contemporary trends in etiology, diagnosis, management, and outcome of
      SBO and to draw the clinician's attention on this probably underestimated
      disease. Over a 6-year period we performed this systematic study in an academic
      quaternary medical care and skull base center including 20 patients (mean age
      63.7 years) with central SBO, which is one of the largest series from a single
      center. In contrast to previous studies we explicitly excluded infections limited
      to malignant external otitis only but did not restrict central SBO to conditions
      unrelated to aural pathology. Fifteen patients had otogenic and five sinugenic
      SBO; four patients had fungal or mixed fungal infections. Pre-existing illnesses
      altering bone vascularization were detected in 70 % of the patients and had a
      negative effect on the improvement of cranial nerve palsies that were found in 14
      patients. In relation, patients with otogenic SBO more often had local and
      systemic predisposing factors. Contrary to previous studies 16 patients (80 %)
      underwent surgical therapy and none of our patients died. A meta-analysis of five
      recent studies was done and compared with our own data and two previous meta
      analyses. The present study highlights several important aspects with major
      implications for diagnosis and treatment of SBO that have not been adequately
      addressed as yet. In contrast to the restrictive attitude towards surgery in
      literature we recommend early and radical operative treatment to reduce its
      mortality.

PMID- 25381581
TI  - Suicide in Three East African Pastoralist Communities and the Role of Researcher
      Outsiders for Positive Transformation: A Case Study.
AB  - We examine cultural understandings and practices surrounding suicide in Pokot,
      Samburu, and Turkana pastoralists in north-central Kenya--three geographically
      overlapping and mutually interacting pastoralist communities. We collected our
      data in the context of a study of poverty, violence, and distress. In all three
      communities, stigma associated with suicide circumscribed individual responses to
      the World Health Organization's Self-Report Questionnaire, which led to an
      ethnographic sub-study of suicide building upon our long-standing research in
      East Africa on distress, violence, and death. As is true for most of sub-Saharan
      Africa, reliable statistical data are non-existent for these communities. Thus,
      we deliberately avoid making assertions about generalizable statistical trends.
      Rather, we take the position that ethnographically nuanced studies like the one
      we offer here provide a necessary basis for the respectful collection of accurate
      quantitative data on this important and troubling practice. Moreover, our central
      point in this paper is that positive transformational work relating to suicide is
      most likely when researcher outsiders practice 'deep engagement' while
      respectfully restricting their role to (1) iterative, community-driven approaches
      that contextualize suicide; and (2) sharing contextualized analyses with other
      practitioners. We contend that situating suicide within a broader cultural
      framework that includes attitudes and practices surrounding other forms of death
      is essential to both aspects of anthropological-outsiders' role.

PMID- 25381582
TI  - PCDD/Fs in the soils in the province of Trento: 10 years of monitoring.
AB  - This paper presents a 10-year overview of the dioxins and furans (PCDD/Fs)
      content in soils in the province of Trento (Italy). The aim was to compare the
      results found in the Valsugana valley where there is a steel-making plant with
      other locations within the province. During 2002 and from 2005 to 2010, campaigns
      were carried out in order to obtain a background reference in terms of
      micropollutants, in view of the possible construction of a municipal solid waste
      (MSW) incinerator in Trento. In 2009, a campaign was performed for the
      environmental characterization of the Valsugana valley, the town of Trento and
      its surroundings, in order to help assess the impact of the steel-making plant.
      In 2012, another campaign was carried out by the Department of Civil and
      Environmental Engineering of Trento, in order to monitor the soils in the area
      around the steel mill. All the campaigns showed relatively low concentrations of
      PCDD/Fs, both in protected areas and in the areas close to the industrial plants.
      No critical situations were identified, as also confirmed by an estimation of the
      potential daily PCDD/F intake by children subject to accidental ingestion of
      soil. 

PMID- 25381583
TI  - Sewage sludge and fly ash mixture as an alternative for decontaminating lead and
      zinc ore regions.
AB  - Many years of heavy industrial processes in the Upper Silesian Industrial Region
      in Poland (ore flotation, metal smelting and battery scrap processing) have
      resulted in lead, zinc and cadmium pollution of the air and soil. The most
      significant issues stem not only from elevated levels of these metals in
      environmental compartments, but also from the uneven pattern of their
      distribution. Point sources of local metal concentration are to be found
      dispersed over areas of contaminated soil. Such distribution is a challenge for
      remediation technology, as it precludes the introduction of standard procedures.
      Metals present in the soil pose a constant risk for living organisms. One of the
      most effective ways of limiting their ecological impact is by decreasing their
      mobility. In this study, the effect of introducing sewage sludge and fly ash
      mixtures (sluash material) into contaminated soil was evaluated. We tested the
      mixture in terms of the probability of its ecotoxicological impact on plant
      growth and development. The data obtained have shown that even low doses (3%) of
      sluash are effective in reducing the bioavailability of lead, cadmium and zinc,
      resulting in a decrease of their concentration in plants. The application of
      sluash also led to stabilize soil pH. It also had a positive impact on the total
      number of soil bacteria and soil fungi.

PMID- 25381584
TI  - Determination of cadmium in biodiesel using microemulsion and electrothermal
      atomization atomic absorption spectrometry.
AB  - This work aimed to prepare biodiesel microemulsions for the subsequent
      quantification of cadmium via graphite furnace atomic absorption spectrometry
      (GFAAS). The biodiesel samples were prepared using n-propanol as an emulsifier,
      10% (v/v) nitric acid as the aqueous phase, and biodiesel. Pseudoternary phase
      diagrams were constructed to determine the microemulsion region with the
      specified components. The optimized conditions for microemulsion formation were
      57.6% (v/v) n-propanol, 21.2% (v/v) biodiesel, and 21.2% (v/v) nitric acid
      solution. The stability of the microemulsified system was investigated using
      aqueous and organic standards, and the system was found to be stable for at least
      240 min. The applied pyrolysis and atomization temperatures were 800 and 2000 
      degrees C, respectively, and 5 MUg of aluminum was used as the chemical modifier.
      The obtained limits of detection and quantification were 0.2 and 0.5 MUg kg(-1),
      respectively, and the characteristic mass was 1.6 pg. The precision, expressed as
      the relative standard deviation (% R.S.D., n = 10), was 2.5% for a sample with a
      cadmium concentration of 6.5 MUg kg(-1). The accuracy was determined from
      addition and recovery experiments, with results varying from 93 to 108% recovery.
      This study demonstrates that the proposed method based on the use of a
      microemulsion formation in sample preparation can be applied as an efficient
      alternative for the determination of cadmium in biodiesel by GFAAS. Cadmium
      determination in biodiesel samples of different origins (soybean, corn, cotton,
      and sunflower) was evaluated after acid digestion using the inductively coupled
      plasma-mass spectrometry (ICP-MS) technique, and the obtained results were
      compared to the results obtained using the proposed method. The paired t test
      (95% confidence level) did not show significant differences. The concentrations
      of cadmium found ranged from 5.3 to 8.0 MUg kg(-1).

PMID- 25381585
TI  - Adsorption and leaching behaviour of bispyribac-sodium in soils.
AB  - Adsorption-desorption of the herbicide bispyribac-sodium was studied in four
      Indian soil types. Bispyribac-sodium was poorly adsorbed in the four soils and
      adsorption decreased with an increase in the herbicide concentration in solution.
      Freundlich adsorption coefficient (Kf) values for bispyribac-sodium ranged
      between 0.37 and 0.87. Slope (1/n) values varied from 0.2 to 0.31 suggesting that
      bispyribac-sodium adsorption was highly dependent on its initial concentration in
      solution. Bispyribac-sodium adsorption showed a positive correlation with soil pH
      (r = 0.809) and clay content (r = 0.699) while no correlation was observed with
      the organic carbon (r = 0.063) content. Sorbed herbicide was completely desorbed
      during a single desorption step suggesting that the herbicide was bound by weak
      adsorptive forces. Leaching studies of herbicide in soil 1 packed column
      indicated complete loss of soil applied herbicide under a simulated rainfall
      equivalent to 162 mm.

PMID- 25381586
TI  - MicroRNA-21 regulates the sensitivity to cisplatin in a human osteosarcoma cell
      line.
AB  - BACKGROUND: Recent studies have shown that microRNA-21 (miR-21) is overexpressed
      in solid tumors and implicated in the modulation of drug-induced resistance.
      METHODS: In this study, we investigated the anti-tumor effects of miR-21 on the
      sensitivity of osteosarcoma cells to CDDP. RESULTS: Changes in the sensitivity of
      osteosarcoma cells to CDDP were examined after transfection with miR-21 mimics or
      anti-miR-21 or bcl-2 siRNA in combination with CDDP. Osteosarcoma cells
      transfected with miR-21 mimics were significantly resistant to CDDP, while
      suppression of miR-21 in osteosarcoma cells led to enhanced CDDP cytotoxicity.
      Moreover, the miR-21-induced changes in chemoresponse were ameliorated by down
      regulation of bcl-2 by its siRNA. CONCLUSION: The miR-21 in osteosarcoma cells is
      a significant modulator of the anti-tumor effect of CDDP by regulating the
      expression of bcl-2, and the study reveals a novel mechanism of osteosarcoma drug
      resistance.

PMID- 25381588
TI  - Single-site laparoscopic appendectomy in children using conventional instruments:
      a prospective, randomized, control trial.
AB  - PURPOSE: Single-site laparoscopic surgery (SSLS) is still only used in limited
      situations to treat children with appendicitis. Using conventional laparoscopic
      (CL) equipment to perform SSLS appendectomy is considered a valuable application
      in China. This prospective randomized trial aims to evaluate the surgical outcome
      of SSLS and CL appendectomy using CL equipment. METHODS: Sixty patients were
      recruited and randomly assigned to receive SSLS or 3-port CL appendectomy between
      February 2011 and June 2013. Each case of SSLS appendectomy was performed using
      CL instruments. Surgery outcomes, including operative time, conversion rates,
      postoperative complications, hospital stays, and hospital costs were evaluated.
      RESULTS: Patient characteristics were similar between groups. The SSLS using CL
      instruments was successful in all the 30 patients and no conversions occurred.
      Mean operative time was longer in the SSLS group than the CL group (64.3 +/- 3.1
      vs 53.0 +/- 2.9 min, respectively; p = 0.000). Complication rates, lengths of
      hospital stay, and hospital costs were similar between the two groups.
      CONCLUSIONS: The findings of this study demonstrate that using conventional
      instruments to perform SSLS is technically feasible and safe in children.
      Although SSLS appendectomy does increase the operative time, it does not increase
      the complication rate and hospital cost.

PMID- 25381589
TI  - Inguinal hernia in neonates and ex-preterm: complications, timing and need for
      routine contralateral exploration.
AB  - BACKGROUND/PURPOSE: Aim of this study was to present a series of neonates and ex
      preterm babies who underwent inguinal hernia repair focusing on complications and
      possible indication to perform routine contralateral groin exploration. METHODS:
      This is a retrospective study of a series of consecutive patients weighing less
      than 5 kg who underwent inguinal hernia repair between January 2007 and December
      2012. Only the affected side was treated. Patients have been routinely followed
      up postoperatively. We resorted to available outpatients' charts and admission
      notes to record demographic data, surgical details, complications and the
      occurrence of metachronous hernias. A questionnaire was administered to all
      patients' relatives to confirm the long-term outcome. RESULTS: One hundred fifty
      four patients were operated for a total of 184 herniotomies (88 right sided, 36
      left sided and 30 bilateral). Median length of follow-up was 42 months (range 6
      months-7.5 years). Thirteen patients (13/124 = 10.5 %) developed metachronous
      hernia that proved to be significantly more frequent in patients weighing less
      than 1,500 g at birth (p < 0.05). We observed 10 % of complications, including
      2.7 % testicular atrophy and 4.5 % recurrence. Atrophy proved to occur more
      frequently in patients who experienced preoperative incarceration (p < 0.05). No
      other risk factors were identified. CONCLUSIONS: The results of our series
      demonstrated that, though technically demanding, herniotomy in the neonate and ex
      preterm is associated with a relatively low incidence of complications. Based on
      our results and in accordance with literature data, we do not advocate routine
      contralateral exploration in case of unilateral hernia but surgery to be
      performed only on the symptomatic side, as soon as possible after initial
      diagnosis. Very low birth weight patients should be followed with care in the
      early postoperative period due to the higher likelihood of developing a
      metachronous hernia.

PMID- 25381590
TI  - Reduced-dose cyclophosphamide in combination with fludarabine and anti-thymocyte
      globulin as a conditioning regimen for allogeneic hematopoietic stem cell
      transplantation for aplastic anemia.

PMID- 25381591
TI  - Bone metastases in gastrointestinal cancer.
AB  - Colorectal (CRC) and gastroesophageal (GEC) cancers unusually spread to the bone.
      However, bone metastases (BM) are responsible for skeletal-related events (SREs)
      associated with an altered quality of life. Aiming to describe the
      characteristics and prognostic influence of BM from gastro-intestinal cancers, we
      performed a retrospective analysis of prospectively collected data in patients
      treated in our institution (1996-2006). 189 patients (5.5 %) developed BM: 79
      with GEC and 110 with CRC. 57 patients had bone-exclusive metastases. In
      univariate analyses, the median time to BM occurrence was correlated with the
      primary tumour (PT) localisation, surgery, histology and TNM staging. However, in
      multivariate analyses, the occurrence delay was significantly shorter only for
      patients with GEC (HR 2.1), N1-2 status (HR 1.9), M1 status (HR 2.4), and
      epidermoid carcinoma (HR 6.0). Pain was the most frequent clinical sign leading
      to BM diagnosis (77.2 %). SRE occurred in 55 % of patients. Median overall
      survivals (OSs) of patients with CRC and GEC were 9.4 months [95 % confidence
      interval (95 % CI) 6.4-11.1] and 3.4 months (95 % CI 2.5-9.0), respectively. In
      univariate analyses, OS was correlated with PT surgery and NM staging, and the
      number of BM. In multivariate analyses, only the PT surgery and the number of BM
      remained correlated with OS. Our results suggest that there may be a subset of
      patients associated with a quicker development of BM. Given their higher risk of
      SRE, they could benefit from an early screening, calling for further prospective
      studies encompassing patients with and without BM.

PMID- 25381592
TI  - Long-term results of the uncemented acetabular component in a primary total hip
      arthroplasty performed for protrusio acetabuli: a fifteen year median follow-up.
AB  - PURPOSE: Protrusio acetabuli is an uncommon finding that can be seen in patients
      undergoing primary total hip arthroplasty for arthritis. Uncemented fixation of
      the acetabular component and bone grafting of the protrusio defect is commonly
      used as a reconstruction method and has shown good mid-term results. The long
      term outcome of these reconstructions warrants further study. The objective of
      this study was to determine the results of primary total hip arthroplasty (THA)
      with use of an uncemented acetabular component for protrusio acetabuli in
      patients followed for a minimum of ten years. METHODS: Sixty-five hips in 53
      patients had a primary THA with uncemented acetabular component for the protrusio
      acetabuli between 1984 and 2001. There were 53 procedures performed in females
      (82%) and 12 in males (18%). The mean age at the procedure was 66 years.
      Acetabular floor reconstruction with use of bone graft was performed in 58 hips
      (89%). Four patients (five hips) were lost to follow-up less than ten years after
      the procedure and 25 patients (31 hips) had died during the follow-up period. The
      median follow-up of living patients that did not have revisions for acetabular
      component was 15.4 years (range, ten to 24 years). RESULTS: During the study
      duration, six hips underwent acetabular component revision: aseptic loosening
      (three hips), polyethylene wear (two hips), and recurrent instability (one hip).
      The median Harris hip score for the living patients who did not have an
      acetabular component revision improved from 55 points pre-operatively to 82
      points at the latest follow-up. At 15 years, the estimated survival rate from
      revision was 70% for the THA: 85.4% for the acetabular component, and 83% for the
      femoral component. Five unrevised acetabular components had evidence of non
      progressive radiolucency. CONCLUSIONS: In patients undergoing THA with acetabular
      protrusio, fixation of an uncemented hemispherical shell and use of bone graft as
      necessary provided satisfactory clinical and radiographic results as well as
      satisfactory survivorship rates at a median follow-up of 15 years.

PMID- 25381593
TI  - Comparison of posterior foraminotomy and anterior foraminotomy with fusion for
      treating spondylotic foraminal stenosis of the cervical spine: study protocol for
      a randomized controlled trial (ForaC).
AB  - BACKGROUND: Cervical radiculopathy caused by spondylotic foraminal stenosis may
      require surgical treatment. Surgical options include anterior cervical
      foraminotomy and fusion or posterior cervical foraminotomy. Controversy remains
      regarding the preferable surgical approach. Pertinent clinical evidence is
      limited to low-quality observational reports. Therefore, treatment decisions are
      predominantly based on the individual surgeon's preference and skill. The study
      objective is to evaluate the efficacy and safety of posterior foraminotomy in
      comparison to anterior foraminotomy with fusion for the treatment of spondylotic
      foraminal stenosis. METHODS/DESIGN: This is a multicenter randomized, controlled,
      parallel group superiority trial. A total of 88 adult patients are allocated in a
      ratio of 1:1. Sample size and power calculations were performed to detect the
      minimal clinically important difference of 14 points, with an expected standard
      deviation of 20 in the primary outcome parameter, Neck Disability Index, with a
      power of 80%, based on an assumed maximal dropout rate of 20%. Secondary outcome
      parameters include the Core Outcome Measures Index, which investigates pain, back
      specific function, work disability, social disability and patient satisfaction.
      Changes in physical and mental health are evaluated using the Short Form-12 (SF
      12) questionnaire. Moreover, radiological and health economic outcomes are
      evaluated. Follow-up is performed 3, 6, 12, 24, 36, 48 and 60 months after
      surgery. Major inclusion criteria are cervical spondylotic foraminal stenosis
      causing radiculopathy of C5, C6 or C7 and requiring decompression of one or two
      neuroforaminae. Study data generation (study sites) and data storage, processing
      and statistical analysis (Department of Medical Statistics, Informatics and
      Health Economics) are clearly separated. Data will be analyzed according to the
      intention-to-treat principle. DISCUSSION: The results of the ForaC study will
      provide surgical treatment recommendations for spondylotic foraminal stenosis and
      will contribute to the understanding of its short- and long-term clinical and
      radiological postoperative course. This will hopefully translate into
      improvements in surgical treatment and thus, clinical practice for spondylotic
      foraminal stenosis. TRIAL REGISTRATION: Current Controlled Trials:
      ISRCTN82578069.

PMID- 25381594
TI  - Streptolysin S of Streptococcus anginosus exhibits broad-range hemolytic
      activity.
AB  - Streptococcus anginosus is a commensal of mucous membranes and an emerging human
      pathogen. Some strains, including the type strain, display a prominent beta
      hemolytic phenotype. A gene cluster (sag), encoding a variant of streptolysin S
      (SLS) has recently been identified as the genetic background for beta-hemolysin
      production in S. anginosus. In this study, we further characterized the hemolytic
      and cytolytic activity of the S. anginosus hemolysin in comparison with other
      streptococcal hemolysins. The results indicate that SLS of S. anginosus is a
      broad-range hemolysin able to lyse erythrocytes of different species, including
      horse, bovine, rabbit and even chicken. The hemolytic activity is temperature
      dependent, and a down-regulation of the hemolysin expression is induced in the
      presence of high glucose levels. Survival assays indicate that in contrast to
      other streptococcal species, S. anginosus does not require SLS for survival in
      the presence of human granulocytes. Cross-complementation studies using the sagB
      and sagD genes of Streptococcus pyogenes and Streptococcus dysgalactiae subsp.
      equisimilis demonstrated functional similarities to the S. anginosus SLS.
      Nevertheless, distinct differences to other streptolysin S variants were noted
      and provide further insights into the molecular mechanisms of SLS pathogen host
      interactions. 

PMID- 25381595
TI  - Characterization and high expression of recombinant Ustilago maydis xylanase in
      Pichia pastoris.
AB  - A recombinant xylanase gene (rxynUMB) from Ustilago maydis 521 was expressed in
      Pichia pastoris, and the enzyme was purified and characterized. Phylogenetic
      analysis demonstrated that rxynUMB belongs to glycosyl hydrolase family 11. The
      Trp84, Trp95, Glu93, and Glu189 residues are proposed to be present at the active
      site. The apparent molecular mass of the recombinant xylananse was approximately
      24 kDa, and the optimum pH and temperature were 4.3 and 50  degrees C,
      respectively. Xylanase activity was enhanced by 166 and 115% with Fe(2+) and
      Mn(2+), respectively. The biochemical properties of this recombinant xylanase
      suggest that it may be a useful candidate for a variety of commercial
      applications.

PMID- 25381596
TI  - Production of a low calorie mandarin juice by enzymatic conversion of constituent
      sugars to oligosaccharides and prevention of insoluble glucan formation.
AB  - Over 99% of sucrose in mandarin juice (57.1 g/l in original juice to 428.4 g/l in
      concentrated juice) was enzymatically converted to glucooligosaccharides using 3
      U dextransucrase/ml prepared from Leuconostoc mesenteroides at 28  degrees C. The
      oligosaccharide synthesis yields were 51 and 47% for the original and the
      concentrated mandarin juice, respectively. The degree of polymerization of
      oligosaccharides in the enzyme-modified juice was 2-7. Calories in the original
      and modified mandarin juice were 433 and 301 kcal/l (30.5% reduction). Compared
      with the original juice, the enzyme-modified juice showed 82% decrease of
      insoluble glucan formation by mutansucrase from Streptococcus mutans. A sensory
      evaluation of the juices revealed that the original and modified mandarin juices
      had sweetness values of 4.5 and 4.9 and the same values for overall
      acceptability.

PMID- 25381597
TI  - Revisiting the Time Trade-Off Hypothesis: Work, Organized Activities, and
      Academics During College.
AB  - How adolescents spend their time has long-term implications for their
      educational, health, and labor market outcomes, yet surprisingly little research
      has explored the time use of students across days and semesters. The current
      study used longitudinal daily diary data from a sample of college students
      attending a large public university in the Northeastern US (n = 726, M age =
      18.4) that was followed for 14 days within each of seven semesters (for up to 98
      diary days per student). The study had two primary aims. The first aim was to
      explore demographic correlates of employment time, organized activity time, and
      academic time. The second aim was to provide a rigorous test of the time trade
      off hypothesis, which suggests that students will spend less time on academics
      when they spend more time on employment and extracurricular activities. The
      results demonstrated that time use varied by gender, parental education, and
      race/ethnicity. Furthermore, the results from multi-level models provided some
      support for the time trade-off hypothesis, although associations varied by the
      activity type and whether the day was a weekend. More time spent on employment
      was linked to less time spent on academics across days and semesters whereas
      organized activities were associated with less time on academics at the daily
      level only. The negative associations between employment and academics were most
      pronounced on weekdays. These results suggest that students may balance certain
      activities across days, whereas other activities may be in competition over
      longer time frames (i.e., semesters). 

PMID- 25381599
TI  - Association study of single nucleotide polymorphisms in mature microRNAs and the
      risk of thyroid tumor in a Chinese population.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that are involved in a
      variety of cellular functions. Single nucleotide polymorphisms (SNPs) have been
      identified in mature miRNAs (mmSNPs), some of which have been linked to cancer
      risk; however, it is unclear which mmSNPs contribute to the susceptibility to
      thyroid tumors. In the present study, we examined the influence of selected
      mmSNPs on the risk of thyroid tumor. After systematic in silico screening,
      seventeen mmSNPs were identified and genotyped in a Chinese population including
      828 patients with papillary thyroid cancer (PTC), 488 patients with benign
      thyroid tumor (BN), and 1038 cancer-free controls. Multivariate logistic
      regression analyses were conducted to evaluate the association of SNP genotypes
      and alleles with the risk of developing PTC and BN. Three SNPs (rs67106263 in mir
      3144, GA versus GG, OR = 1.35, 1.09-1.68; rs4919510 in mir-608, CC versus GG/GC,
      OR = 0.76, 0.60-0.97; and rs79402775 in mir-933, AA versus GG/GA, OR = 1.76, 1.00
      3.12) were associated with PTC risk. A combined effect of unfavorable genotypes
      was observed to give increased PTC risk in a dose-dependent manner. In addition,
      three SNPs (rs10061133 in mir-449b, rs79402775 in mir-933 and rs4919510 in mir
      608) showed at least borderline correlations with the risk of BN. False-positive
      report probability was assessed for significant findings. The rs67106263 SNP was
      associated with the expression level of mir-3144 in thyroid tissue. These results
      indicate that mmSNPs may contribute to genetic susceptibility to thyroid tumors.
      Large validation and functional studies are required to further explore the role
      of mmSNPs in carcinogenesis.

PMID- 25381598
TI  - MicroRNA expression profiling and Notch1 and Notch2 expression in minimal
      deviation adenocarcinoma of uterine cervix.
AB  - BACKGROUND: MicroRNA (miRNA) expression is known to be deregulated in cervical
      carcinomas. However, no data is available about the miRNA expression pattern for
      the minimal deviation adenocarcinoma (MDA) of uterine cervix. We sought to detect
      deregulated miRNAs in MDA in an attempt to find the most dependable miRNA or
      their combinations to understand their tumorigenesis pathway and to identify
      diagnostic or prognostic biomarkers. We also investigated the association between
      those miRNAs and their target genes, especially Notch1 and Notch2. METHODS: We
      evaluated miRNA expression profiles via miRNA microarray and validated them
      using.real-time PCR assays with 24 formalin-fixed, paraffin-embedded tissue
      blocks of MDA and 11 normal proliferative endocervical tissues as control.
      Expression for Notch1 and 2 was assessed by immunohistochemistry. RESULTS: MiRNA
      135a-3p, 192-5p, 194-5p, and 494 were up-regulated, whereas miR-34b-5p, 204-5p,
      299-5p, 424-5p, and 136-3p were down-regulated in MDA compared with normal
      proliferative endocervical tissues (all P<0.05). Considering the second-order
      Akaike Information Criterion consisting of likelihood ratio and number of
      parameters, miR-34b-5p showed the best discrimination power among the nine
      candidate miRNAs. A combined panel of miR-34b-5p and 194-5p was the best fit
      model to discriminate between MDA and control, revealing 100% sensitivity and
      specificity. Notch1 and Notch2, respective target genes of miR-34b-5p and miR-204
      5p, were more frequently expressed in MDA than in control (63% vs. 18%; 52% vs.
      18%, respectively, P<0.05). MiR-34b-5p expression level was higher in Notch1
      negative samples compared with Notch1-positive ones (P<0.05). Down-regulated miR
      494 was associated with poor patient survival (P=0.036). CONCLUSIONS: MDA showed
      distinctive expression profiles of miRNAs, Notch1, and Notch2 from normal
      proliferative endocervical tissues. In particular, miR-34b-5p and 194-5p might be
      used as diagnostic biomarkers and miR-494 as a prognostic predictor for MDA. The
      miR-34b-5p/Notch1 pathway as well as Notch2 might be important oncogenic
      contributors to MDA.

PMID- 25381600
TI  - Identification of a novel germline FOXE1 variant in patients with familial non
      medullary thyroid carcinoma (FNMTC).
AB  - The familial forms of non-medullary thyroid carcinoma (FNMTC) represent
      approximately 5 % of thyroid neoplasms. Nine FNMTC susceptibility loci have been
      mapped; however, only the DICER1 and SRGAP1 susceptibility genes have been
      identified. The transcription factors NKX2-1, FOXE1, PAX8, and HHEX are involved
      in the morphogenesis and differentiation of the thyroid. Recent studies have
      identified NKX2-1 germline mutations in FNMTC families. However, the role of high
      penetrant FOXE1 variants in FNMTC etiology remains unclear. The aim of this study
      was to investigate the role of FOXE1 germline mutations in the pathogenesis of
      FNMTC. We searched for molecular changes in the FOXE1 gene in the probands from
      60 Portuguese families with FNMTC. In this series, we identified nine
      polymorphisms and one variant (c.743C>G, p.A248G) which was not previously
      described. This variant, which involved an amino acid residue conserved in
      evolution, segregated with disease in one family, and was also detected in an
      apparently unrelated case of sporadic NMTC. Functional studies were performed
      using rat normal thyroid cells (PCCL3) clones and human papillary thyroid
      carcinoma cell line (TPC-1) pools, expressing the wild type and mutant (p.A248G)
      forms of FOXE1. In these experiments, we observed that the p.A248G variant
      promoted cell proliferation and migration, suggesting that it may be involved in
      thyroid tumorigenesis. Additionally, somatic p.V600E BRAF mutations were also
      detected in the thyroid tumors of two members of the family carrying the p.A248G
      variant. This study represents the first evidence of involvement of a germline
      FOXE1 rare variant in FNMTC etiology and suggests that mutations in MAPK pathway
      related genes may contribute to tumor development in these familial cases.

PMID- 25381601
TI  - Alteration of the growth hormone axis, visceral fat dysfunction, and early
      cardiometabolic risk in adults: the role of the visceral adiposity index.
AB  - The aim of the study is to clarify the relationship between adipose tissue
      dysfunction, metabolic profile and growth hormone (GH)/insulin-like growth factor
      (IGF)-I secretion in healthy adult subjects. We investigated the metabolic
      profile in a cohort of 231 consecutive healthy subjects in relation to GH, IGF-I
      levels, and visceral adiposity index (VAI). Anthropometric measures, lipid
      profile, and glucose and insulin levels during oral glucose tolerance test, Homa
      IR and ISI Matsuda, IGF-I and GH peak after GHRH plus Arginine test were
      analyzed. The subjects with high VAI showed lower GH peak (22.8 +/- 11.1 vs. 42.2
      +/- 21.3 ug/L; p = 0.049) and lower IGF-I (presented as IGF-I under normal range,
      UNR) (0.54 +/- 0.14 vs. 0.64 +/- 0.12; p = 0.005) than group with normal VAI. ROC
      curve analysis identified the cut-off, able to detect subjects with high VAI,
      i.e., 31.8 ug/L for GH peak and 0.63 for IGF-1 UNR. The subjects with GH peak and
      IGF-I UNR under the cut-off showed significantly higher levels of VAI, systolic
      and diastolic blood pressure, glucose and insulin levels, Homa-IR, and lower ISI
      Matsuda, with a concomitant worse lipid profile (all p < 0.001). A strong
      relationship between GH axis, VAI and metabolic risk has been demonstrated. A
      percentage of apparently healthy subjects show a degree of visceral adipose
      dysfunction associated with GH and IGF-I levels that do not meet the criteria of
      overt GH deficiency (GHD). Long-term prospective studies could help to clarify
      and confirm whether a hypothetical condition of subclinical GHD could be taken
      into account as a new clinical entity.

PMID- 25381602
TI  - Subclinical hyperthyroidism increases risk of coronary heart disease events in
      type 2 diabetes mellitus.

PMID- 25381603
TI  - Association between circulating irisin and homocysteine in patients with
      nonalcoholic fatty liver disease.

PMID- 25381604
TI  - Pituitary stalk interruption and olfactory bulbs aplasia/hypoplasia in a man with
      Kallmann syndrome and reversible gonadotrope and somatotrope deficiencies.

PMID- 25381606
TI  - Kinetic and stoichiometric characterization for efficient enhanced biological
      phosphorus removal (EBPR) process at high temperatures.
AB  - A recently reported stable and efficient EBPR system at high temperatures around
      30  degrees C has led to characterization of kinetic and stoichiometric
      parameters of the Activated Sludge Model no. 2d (ASM2d). Firstly, suitable model
      parameters were selected by identifiability analysis. Next, the model was
      calibrated and validated. ASM2d was found to represent the processes well at 28
      and 32  degrees C except in polyhyroxyalkanoate (PHA) accumulation of the latter.
      The values of the kinetic parameters for PHA storage (q PHA), polyphosphate
      storage (q PP) and growth (MU PAO) of polyphosphate-accumulating organisms (PAOs)
      at 28 and 32  degrees C were found to be much higher than those reported by
      previous studies. Besides, the value of the stoichiometric parameter for the
      requirement of polyphosphate for PHA storage (Y PO4) was found to decrease as
      temperature rose from 28 to 32  degrees C. Values of two other stoichiometric
      parameters, i.e. the growth yield of heterotrophic organisms (Y H) and PAOs (Y
      PAO), were high at both temperatures. These calibrated parameters imply that the
      extremely active PAOs of the study were able to store PHA, store polyphosphate
      and even utilize PHA for cell growth. Besides, the parameters do not follow the
      Arrhenius correlation due to the previously reported unique microbial clade at 28
      and 32  degrees C, which actively performs EBPR at high temperatures. 

PMID- 25381605
TI  - Can behavioral theory inform the understanding of depression and medication
      nonadherence among HIV-positive substance users?
AB  - Medication adherence is highly predictive of health outcomes across chronic
      conditions, particularly HIV/AIDS. Depression is consistently associated with
      worse adherence, yet few studies have sought to understand how depression relates
      to adherence. This study tested three components of behavioral depression theory-
      goal-directed activation, positive reinforcement, and environmental punishment-
      as potential indirect effects in the relation between depressive symptoms and
      medication nonadherence among low-income, predominantly African American
      substance users (n = 83). Medication nonadherence was assessed as frequency of
      doses missed across common reasons for nonadherence. Non-parametric bootstrapping
      was used to evaluate the indirect effects. Of the three intermediary variables,
      there was only an indirect effect of environmental punishment; depressive
      symptoms were associated with greater nonadherence through greater environmental
      punishment. Goal-directed activation and positive reinforcement were unrelated to
      adherence. Findings suggest the importance of environmental punishment in the
      relation between depression and medication adherence and may inform future
      intervention efforts for this population.

PMID- 25381607
TI  - Lamivudine treatment and outcome in pregnant women with high hepatitis B viral
      loads.
AB  - Perinatal transmission is the most common mode of hepatitis B virus (HBV)
      transmission and is a leading cause of chronic infection worldwide. Maternal
      treatment with lamivudine (LAM) can result in a rapid and significant reduction
      in HBV viral load (VL) and, thus, mitigate the risk of mother-to-child
      transmission (MTCT). The aim of this study was to retrospectively evaluate the
      safety of LAM treatment administered in the third trimester of pregnancy and
      determine the influence, if any, on infant outcome. The medical charts of all HBV
      surface antigen (HBsAg)-positive women eligible for treatment with LAM and who
      registered for antenatal care between 2007 and 2012 were retrospectively
      reviewed. During the 6-year period, 45 women met the criteria for LAM treatment.
      Thirty-six women (80 %) accepted treatment; the remaining women declined
      treatment (5), defaulted from care (3) or transferred to another maternity unit
      (1). The median duration of treatment was 11.4 weeks (range 5.3-17.4) and the
      median baseline VL was 1.4 * 10(8) IU/mL (range 1.8 * 10(7)-1.7 * 10(8)). The
      median VL at delivery was 2.3 * 10(5) IU/mL and 60 % of women achieved a VL
      reduction >2 log10 IU/mL before delivery. No cases of perinatal transmission
      occurred in the infants born to mothers who received treatment; however, one
      infant, born to a mother who defaulted from care, was HBV-infected at 8 months.
      The results suggest that LAM therapy in highly viraemic HBV-infected pregnant
      women could lower the rate of vertical transmission. 

PMID- 25381608
TI  - Approaches for the detection of harmful algal blooms using oligonucleotide
      interactions.
AB  - Blooms of microscopic algae in our waterways are becoming an increasingly
      important environmental concern. Many are sources of harmful biotoxins that can
      lead to death in humans, marine life and birds. Additionally, their biomass can
      cause damage to ecosystems such as oxygen depletion, displacement of species and
      habitat alteration. Globally, the number and frequency of harmful algal blooms
      has increased over the last few decades, and monitoring and detection strategies
      have become essential for managing these events. This review discusses
      developments in the use of oligonucleotide-based 'molecular probes' for the
      selective monitoring of algal cell numbers. Specifically, hybridisation
      techniques will be a focus. 

PMID- 25381609
TI  - Direct extraction of genomic DNA from maize with aqueous ionic liquid buffer
      systems for applications in genetically modified organisms analysis.
AB  - To date, the extraction of genomic DNA is considered a bottleneck in the process
      of genetically modified organisms (GMOs) detection. Conventional DNA isolation
      methods are associated with long extraction times and multiple pipetting and
      centrifugation steps, which makes the entire procedure not only tedious and
      complicated but also prone to sample cross-contamination. In recent times, ionic
      liquids have emerged as innovative solvents for biomass processing, due to their
      outstanding properties for dissolution of biomass and biopolymers. In this study,
      a novel, easily applicable, and time-efficient method for the direct extraction
      of genomic DNA from biomass based on aqueous-ionic liquid solutions was
      developed. The straightforward protocol relies on extraction of maize in a 10 %
      solution of ionic liquids in aqueous phosphate buffer for 5 min at room
      temperature, followed by a denaturation step at 95  degrees C for 10 min and a
      simple filtration to remove residual biopolymers. A set of 22 ionic liquids was
      tested in a buffer system and 1-ethyl-3-methylimidazolium dimethylphosphate, as
      well as the environmentally benign choline formate, were identified as ideal
      candidates. With this strategy, the quality of the genomic DNA extracted was
      significantly improved and the extraction protocol was notably simplified
      compared with a well-established method. 

PMID- 25381610
TI  - Development of a multi-residue method in a fetal matrix: analysis of meconium.
AB  - Meconium is the earliest stool of newborns. It is a complex matrix that reflects
      the degree of fetal exposure to environmental pollutants. To investigate exposure
      to xenobiotics, an analytical method was developed to identify and quantify some
      pesticides and their metabolites and BTEX metabolites in meconium. Samples were
      prepared by two liquid-solid extractions and purified twice using SPE cartridges,
      followed by analysis with liquid chromatography coupled with tandem mass
      spectrometry. SPE cartridges (polymeric phase with hydrophilic and hydrophobic
      interactions, ion exchange, mixed mode) were tested and matrix effects were
      evaluated to determine purification performance. The quantification limits in
      meconium of this multi-residue method were in the range of 30 ng g(-1). The
      analytical method was applied to "real" meconium samples. Some target analytes
      were determined in most samples. 

PMID- 25381611
TI  - Application of metabonomic strategy to discover an unreported active ingredient
      in LiuWeiDiHuang pills suppressing beta-glucuronidase.
AB  - Identification of the bioactive ingredient from traditional Chinese medicine
      (TCM) remains a challenging task by traditional approach that focuses on chemical
      isolation coupled with biological activity screening. Here, we present a
      metabonomics-based approach for bioactive ingredient discovery in LiuWeiDiHuang
      pills (LWPs). First, a non-targeted high-performance liquid chromatography
      ultraviolet (HPLC-UV) profiling of rat urine was used to discriminate urinary
      profiling intervened by LWPs. Orthogonal partial least-squares discriminant
      analysis (OPLS-DA) revealed that eight chromatographic peaks made a significant
      contribution to the classification of the LWPs group and the control group. Five
      of these chromatographic peaks were successfully isolated and identified as
      hippurate, genistein (GT), daidzein (DZ), and glucuronide conjugate of GT and
      that of DZ by mass spectroscopy (MS). Subsequently, we found that LWPs
      significantly decreased the activity of intestinal beta-glucuronidase by 18 % and
      exerted a dose-dependent inhibitory effect on rat liver lysosomal fraction,
      suggesting that LWPs were a beta-glucuronidase inhibitor. In the end, by
      inhibiting beta-glucuronidase-guided isolation, D-glucaro-1,4-lactone, a
      previously unreported ingredient of LWPs, was identified by MS, MS/MS, and
      nuclear magnetic resonance spectroscopy. Our findings indicated that metabonomics
      might increase research productivity toward the drug targets and/or bioactive
      compounds from TCM. 

PMID- 25381612
TI  - LC/MS lipid profiling from human serum: a new method for global lipid extraction.
AB  - Over the last decade, technological advances have improved the sensitivity and
      selectivity of LC/MS analyzers, providing very efficient tools for lipidomics
      research. In particular, the nine lipid classes that constitute 99 % of the human
      serum lipidome (sterols, cholesteryl esters, phosphocholines,
      phosphoethanolamines, sphingomyelins, triacylglycerols, fatty acids,
      lysophosphocholines, and diacylglycerols) can be easily detected. However, until
      today there has not been a unique technique for sample preparation that provides
      a satisfactory recovery for all of these nine classes together. In this work, we
      have developed and validated a new one-phase extraction (OPE) method that
      overcomes this limitation. This method was also compared with the gold standard
      lipid extraction methods such as Folch, Bligh & Dyer, and recently developed
      methods with methanol and methyl-tert-butyl ether. Results demonstrate that the
      mixture of methanol/chloroform/MTBE (MMC) provides a recovery very close to 100 %
      for all nine lipid classes of the human serum investigated. For this extraction
      method, 100 MUL of human serum is incubated with 2 mL of the solvents mixture,
      then vortexed and centrifuged. For its simplicity of execution, rapidity,
      reproducibility, and the reduced volume of sample required, this method opens the
      door to the use of human serum lipid profiling for large-scale applications in
      scientific research and clinical trials. 

PMID- 25381613
TI  - Electromigrative separation techniques in forensic science: combining
      selectivity, sensitivity, and robustness.
AB  - In this review we introduce the advantages and limitations of electromigrative
      separation techniques in forensic toxicology. We thus present a summary of
      illustrative studies and our own experience in the field together with
      established methods from the German Federal Criminal Police Office rather than a
      complete survey. We focus on the analytical aspects of analytes' physicochemical
      characteristics (e.g. polarity, stereoisomers) and analytical challenges
      including matrix tolerance, separation from compounds present in large excess,
      sample volumes, and orthogonality. For these aspects we want to reveal the
      specific advantages over more traditional methods. Both detailed studies and
      profiling and screening studies are taken into account. Care was taken to nearly
      exclusively document well-validated methods outstanding for the analytical
      challenge discussed. Special attention was paid to aspects exclusive to
      electromigrative separation techniques, including the use of the mobility axis,
      the potential for on-site instrumentation, and the capillary format for
      immunoassays. The review concludes with an introductory guide to method
      development for different separation modes, presenting typical buffer systems as
      starting points for different analyte classes. The objective of this review is to
      provide an orientation for users in separation science considering using
      capillary electrophoresis in their laboratory in the future. 

PMID- 25381614
TI  - Incorporating yeast biosensors into paper-based analytical tools for
      pharmaceutical analysis.
AB  - Paper-based devices serve to address many analytical questions both inside and
      outside of the laboratory setting. For the first time, yeast is used to construct
      a whole-cell, paper-based biosensor device. This biologically based paper
      analytical device (BioPAD) is sensitive to antibiotics in the tetracycline
      family, and it could potentially address questions of pharmaceutical quality as
      well as antibiotic contamination in liquids. Our BioPAD can qualitatively
      discriminate the presence/absence of doxycycline over a range of 30-10,000
      MUg/mL. In an analysis of a doxycycline dosage form (tablet) commonly used for
      malaria prophylaxis, BioPADs identified the presence of antibiotic with 92 and 95
      % sensitivity, evaluated by eye and computer-assisted image analysis,
      respectively, with no false positives by either method. BioPADs were found to
      remain viable for at least 415 days when stored at 4  degrees C. This research
      demonstrates the utility of whole yeast cells in paper-based pharmaceutical
      testing, and it highlights the potential for the development of yeast-based
      BioPADs to address a range of qualitative analytical questions, especially in low
      resource settings. 

PMID- 25381615
TI  - Metabolomic analysis of avocado fruits by GC-APCI-TOF MS: effects of ripening
      degrees and fruit varieties.
AB  - In order to investigate avocado fruit ripening, nontargeted GC-APCI-TOF MS
      metabolic profiling analyses were carried out. Principal component analysis (PCA)
      and partial least squares discriminant analysis (PLS-DA) were used to explore the
      metabolic profiles from fruit samples of 13 varieties at two different ripening
      degrees. Mannoheptulose; pentadecylfuran; aspartic, malic, stearic, citric and
      pantothenic acids; mannitol; and beta-sitosterol were some of the metabolites
      found as more influential for the PLS-DA model. The similarities among
      genetically related samples (putative mutants of "Hass") and their metabolic
      differences from the rest of the varieties under study have also been evaluated.
      The achieved results reveal new insights into avocado fruit composition and
      metabolite changes, demonstrating therefore the value of metabolomics as a
      functional genomics tool in characterizing the mechanism of fruit ripening
      development, a key developmental stage in most economically important fruit
      crops. 

PMID- 25381616
TI  - Increasing specificity in imaging mass spectrometry: high spatial fidelity
      transfer of proteins from tissue sections to functionalized surfaces.
AB  - Imaging mass spectrometry (IMS) is a technique in full expansion used in many
      clinical and biological applications. A common limitation of the technology,
      particularly true for protein analysis, is that only the most abundant and/or
      more easily ionizable molecules are typically detected. One approach to overcome
      this limitation is to transfer proteins contained within tissue sections onto
      functionalized surfaces with high spatial fidelity for IMS analysis. In this
      case, only proteins with an affinity for the surface will be retained whereas
      others will be removed. The chemical nature of the surface is therefore critical.
      The research work presented herein proposes a high spatial fidelity transfer
      method for proteins from thin tissue sections onto a nitrocellulose surface. The
      method employs a home-built apparatus that allows the transfer process to be
      performed without any direct physical contact between the section and the
      transfer surface while maintaining physical pressure between the surfaces to help
      protein migration. The performance of this system was demonstrated using mouse
      liver and kidney sections. Serials sections were also collected either to be
      stained with hematoxylin and eosin (H&E) to assess the spatial fidelity of the
      transfer process or to be directly analyzed as a control sample to differentiate
      the signals detected after transfer. IMS results showed a high spatial fidelity
      transfer of a subset of proteins. Some of the detected proteins were poorly
      observed or not observed with conventional direct tissue analysis, demonstrating
      an increase in detection sensitivity and specificity with the newly developed
      method. 

PMID- 25381617
TI  - Towards imaging metabolic pathways in tissues.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging
      using 9-aminoacridine as the matrix leads to the detection of low mass
      metabolites and lipids directly from cancer tissues. These included lactate and
      pyruvate for studying the Warburg effect, as well as succinate and fumarate,
      metabolites whose accumulation is associated with specific syndromes. By using
      the pathway information present in the human metabolome database, it was possible
      to identify regions within tumor tissue samples with distinct metabolic
      signatures that were consistent with known tumor biology. We present a data
      analysis workflow for assessing metabolic pathways in their histopathological
      context. 

PMID- 25381618
TI  - A computational study on the photoelectric properties of various Bi2O3 polymorphs
      as visible-light driven photocatalysts.
AB  - This paper presents first-principle studies on the photoelectric properties of
      various Bi2O3 polymorphs. The intrinsic reason of different photocatalytic
      activities was revealed by electronic structures and optical features. Results
      showed that for alpha, beta, and gamma-Bi2O3, the top of valence bands were
      mainly constructed by Bi6s and O2p orbitals, and the bottom of conduction bands
      were dominantly composed by Bi6p orbital. However, two intermediate bands were
      found at the Fermi level for gamma-Bi2O3, which leads to a two-step transition
      from the top of valence band to the bottom of conduction band and facilitates
      electron transition under irradiation. Absent forbidden gap was found in delta
      Bi2O3, resulting in a semimetallic character due to its intrinsic oxygen vacancy
      and high ionic conductivity. Moreover, the optical properties of alpha, beta, and
      gamma-Bi2O3 were investigated by absorption spectrum, dielectric constant
      function, and energy loss spectroscopy. We concluded that the photocatalytic
      activities followed in the order of gamma-Bi2O3 > beta-Bi2O3 > alpha-Bi2O3, in
      accord with the experimental report. Calculation results illustrated the
      experimental observations and provided a useful guidance in exploring promising
      visible-light semiconductor photocatalysts. 

PMID- 25381619
TI  - Protein modeling and molecular dynamics simulation of the two novel surfactant
      proteins SP-G and SP-H.
AB  - Surfactant proteins are well known from the human lung where they are responsible
      for the stability and flexibility of the pulmonary surfactant system. They are
      able to influence the surface tension of the gas-liquid interface specifically by
      directly interacting with single lipids. This work describes the generation of
      reliable protein structure models to support the experimental characterization of
      two novel putative surfactant proteins called SP-G and SP-H. The obtained protein
      models were complemented by predicted posttranslational modifications and placed
      in a lipid model system mimicking the pulmonary surface. Molecular dynamics
      simulations of these protein-lipid systems showed the stability of the protein
      models and the formation of interactions between protein surface and lipid head
      groups on an atomic scale. Thereby, interaction interface and strength seem to be
      dependent on orientation and posttranslational modification of the protein. The
      here presented modeling was fundamental for experimental localization studies and
      the simulations showed that SP-G and SP-H are theoretically able to interact with
      lipid systems and thus are members of the surfactant protein family. 

PMID- 25381620
TI  - Pre-implantation developmental potential from in vivo and in vitro matured mouse
      oocytes: a cytoskeletal perspective on oocyte quality.
AB  - PURPOSE: In the present study, fertilization and developmental potential of mouse
      oocytes matured in different conditions were tested. The efficiency of in vitro
      fertilization (IVF), pre-implantation development and some important aspects of
      cytokinesis during early cleavages are discussed. METHODS: In vivo matured (IVO),
      in vitro matured (IVM) and roscovitine-treated (IVM-Rosco) mouse oocytes were
      subjected to IVF under identical conditions. Three replicates per group were
      analyzed. Fertilization was identified by the presence of two pronuclei at 6-8 h
      post-fertilization. Evaluation of pre-implantation embryonic development was done
      daily from day 2 to day 5 and embryos were processed for analyses of chromatin,
      nuclear lamina, microtubules and centrosomal proteins by conventional and
      confocal fluorescence microscopy. RESULTS: Both IVM groups displayed lower
      fertilization rates when compared to in vivo controls. While IVO-derived embryos
      exhibit efficient and synchronous progression to the blastocyst stage, both IVM
      derived embryos exhibit a delay in embryonic progression, and a lower blastocyst
      rate. Interestingly, IVM-Rosco M-II oocytes exhibited more blastomere symmetries
      and higher number of cells at the blastocyst stage than the IVM group with the
      most notable influence being on the centrosome-microtubule complex of
      blastomeres. CONCLUSION: Our study strongly indicates that when compared to
      spontaneously in vitro matured oocytes, treatment with roscovitine may partially
      enhance developmental competence by maintaining coordination between nuclear and
      cytoplasmic events. Further evidence is given of cytoskeletal biomarkers that can
      be identified during in vitro oocyte maturation conditions.

PMID- 25381621
TI  - Next day determination of ejaculatory sperm motility after overnight shipment of
      semen to remote locations.
AB  - PURPOSE: To develop a method for delayed assessment of sperm motility, after
      shipment of semen to a remote laboratory. Sperm in semen were labeled with the
      MitoTracker((r)) Red CM-H(2)XRos reagent, and fixed with 3.7 % formaldehyde by
      the laboratory technicians at the origin of the semen. This treatment reflected
      well sperm mitochondrial activity, and the MitoTracker((r)) signal was related to
      sperm motility and velocity for 2-3 days following ejaculation. METHODS: Sperm
      motility and velocity were evaluated manually and by computer assisted semen
      analysis (CASA), respectively. Fluorescence assessment of individual sperm was
      carried out with the computer assisted Metamorph v4.6.9 program. Emission levels
      of MitoTracker((r)) spermatozoa were studied in room temperature and cooled
      semen, or in the respective room temperature swim-up sperm fractions following
      ejaculation, and on the second day (N = 103 samples, 89 men) and third day (N =
      10 samples, 8 men). RESULTS: Sperm with optical density (O.D.) >=0.7 showed close
      correlations with ejaculatory sperm motility and velocity even after second day
      (r = 0.92, p < 0.001, N = 103 samples). Further, the multiple of sperm motility
      and velocity was also related to the proportion of high MitoTracker((r)) reagent
      emission sperm (r = 0.83, p < 0.001, N = 103 samples). MitoTracker((r)) dye
      fluorescence on the second day accurately reflected the ejaculatory sperm
      motility (r = 0.90, p < 0.001). Thus, a shipping delay would not adversely affect
      the results. CONCLUSIONS: The delayed assessment of sperm motility in samples
      treated with MitoTracker((r)) Red CM-H(2)XRos reagent and shipped to remote
      laboratory truly reflects the level of sperm motility at the time of the
      ejaculation.

PMID- 25381622
TI  - Survival, re-expansion and cell survival of human blastocysts following
      vitrification and warming using two vitrification systems.
AB  - PURPOSE: This study evaluated and compared survival, re-expansion, and percentage
      of live cells of individual Days 5 and 6 human blastocysts that were vitrified
      and warmed with the Vit Kit Freeze/Thaw (Irvine Scientific, CA), or with two
      protocols using the Global Fast Freeze/Thaw Kits (LifeGlobal, Canada). METHODS:
      Frozen/thawed Day 2-3 or discarded embryos were cultured to blastocyst (culture
      day 5-6). Group 1 blastocysts were vitrified with the Vit Kit (n = 29) and High
      Security Vitrification (HSV) devices. Group 2 (n = 47) and Group 3 (n = 48)
      blastocysts were cryopreserved with the Global Fast Freeze Kit and 0.25 ml
      straws, using a direct plunge or a -100  degrees C holding step, respectively.
      Group 4 (Controls, n = 30) were not vitrified. Blastocysts were subsequently
      cultured for 24 h, assessed for survival and expansion, and then stained
      individually with propidium iodide and Hoechst. Live and total cell number was
      assessed with ImageJ (NIH), and the percentage of live cells calculated for each
      blastocyst. RESULTS: The percentage of live cells was not different between
      vitrified and control (non-vitrified) blastocysts, thus vitrification did not
      affect cell survival. Survival (following thawing and after 24 h culture), re
      expansion, and percentage of live cells were not different for blastocysts
      vitrified and warmed between the two vitrification/warming kits, or between the
      two protocols for the Global Fast Freeze/Thaw Kits. CONCLUSIONS: Blastocyst
      vitrification can be achieved with equal success using simplified protocols and
      cheaper and easy to load freezing straws, providing simultaneously increased
      safety, and efficiency with lower cost, when compared with vitrification using
      specialized embryo vitrification devices.

PMID- 25381623
TI  - Serum Bcl-2 values in children with pulmonary hypertension.
AB  - In this study, we aimed to assess levels of serum B cell lymphoma 2 (sBcl-2) in
      children, which has been implicated in the etiopathogenesis of pulmonary
      hypertension (PH), as well its association with tissue Doppler echocardiographic
      imaging (TDI) data and parameters used in the follow-up of PH. The sBcl-2 level
      was assessed in 35 children with PH (24 had eisenmenger syndrome, and 11 had
      idiopathic PH) and in 38 healthy children as controls. TDI was performed on 25
      patients whose cardiac anatomy allowed the test. The respective sBcl-2 values in
      patients and controls were 35.69 +/- 18.83 and 2.66 +/- 7.95 ng/ml (p < 0.001).
      The sBcl-2 levels were significantly greater in the New York Heart Association
      (NYHA) functional class 3 patients than those in the NYHA class 2 patients (p =
      0.033). The sBcl-2 value in patients who walked <475 m in the 6-min walk distance
      (6MWD) test was significantly greater than in those who walked >=475 m (p =
      0.038). The sBcl-2 level showed a negative correlation with ejection time
      measured at the septal anulus (p = 0.026) and a positive correlation with
      interventricular septum-Tei (p = 0.018). The results of this study showed for the
      first time that there is an increase in the levels of sBcl-2 as an inflammatory
      marker and that the sBcl-2 levels are associated with prognostic parameters in
      children with PH. Because sBcl-2 levels were greater in patients who walked <475
      meters during the 6MWD test, we suggest 475 ms as the cut-off value for the 6MWD
      test to differentiate between a good and a bad prognosis. 

PMID- 25381624
TI  - Outcomes of pediatric patients undergoing cardiac catheterization while on
      extracorporeal membrane oxygenation.
AB  - The aim of the study is to explore the indications for cardiac catheterization
      while on extracorporeal membrane oxygenation (ECMO) and the various catheter
      interventions performed as well as assess the safety profile and determine the
      short- and intermediate-term survival. ECMO is a lifesaving intervention for
      pediatric patients with respiratory and/or cardiovascular failure. There is
      limited recent literature discussing the survival and outcomes of patients
      undergoing cardiac catheterization while on ECMO. A retrospective review of
      consecutive patients undergoing catheterization while on ECMO from 2004 to 2013
      was performed. Thirty-six patients who underwent 40 cardiac catheterizations were
      identified. Indications for catheterization included hemodynamic/anatomic
      assessment of postoperative (16) and non-operative patients (7), planned catheter
      interventions (CI) (12), and cardiomyopathy assessment (5). CI were performed
      during 18 (45 %) catheterizations, including stenting of vessels/surgical shunts
      (9), balloon atrial septostomy (4), device closure of septal defects/vessels (3),
      thrombolysis of vessels (2), endomyocardial biopsy (2), and temporary pacer wire
      placement (1). Unexpected diagnostic information was found in 21 (52 %), and 13
      patients were referred for surgical intervention. Successful decannulation was
      achieved in 86 % of patients. Survival to discharge was 72 % and intermediate
      survival was 69 % (median = 29 months). Survival was 88 % (15/17) among patients
      who underwent CI. There were six procedural complications (15 %); five vascular
      and one non-vascular. There were no complications related to patient transport.
      Cardiac catheterization and interventions while on ECMO are safe, with a survival
      to discharge of 72 %. Diagnostic information obtained from catheterization leads
      to management decisions which may impact survival. 

PMID- 25381625
TI  - Fontan hepatic fibrosis and pulmonary vascular development.
AB  - Fontan patients are at risk for hepatic fibrosis; however, risk factors are
      unclear. We performed a multivariate analysis in a small cohort of 14 patients (7
      24 years old, mean 15) with Fontan circulation, undergoing cardiac
      catheterization and transvenous liver biopsies, all demonstrating fibrosis. We
      found by stepwise regression analysis that the history of pulmonary atresia was a
      predictor of higher total hepatic fibrosis scores than a history of unobstructed
      pulmonary blood flow (p = 0.002). Other variables including age, time from
      Fontan, hemodynamic measurements, and laboratory values were not predictive of
      total fibrosis scores at p values <0.05. Hepatic fibrosis scores between those
      born with pulmonary atresia versus unrestricted pulmonary blood flow may reflect
      differences in pulmonary circulatory physiology, resulting from differences in
      pulmonary vascular development. 

PMID- 25381626
TI  - Commentary on neuromyelitis optica associated with painful paroxysmal dystonia:
      case report and literature review.

PMID- 25381627
TI  - Cockayne syndrome: characteristic neuroimaging features.

PMID- 25381628
TI  - Incidence and prevalence of fetal alcohol spectrum disorder by sex and age group
      in Alberta, Canada.
AB  - OBJECTIVES: To estimate incidence and prevalence of FASD by sex and age in
      Alberta, Canada. METHODS: We included all patients recorded in the Alberta
      provincial health databases of inpatients, outpatients, and practitioner claims
      from 2003 to 2012. The number of people with FASD were calculated from available
      data on FAS (ICD-9 code 760.71; ICD-10 codes Q86.0 and P04.3) and estimated
      prevalence of FASD among individuals diagnosed with 21 FASD-related conditions
      (identified by a literature review) for which there are ICD codes, such as
      learning disability, mental retardation, and nervous system defects (Table 1).
      Fractions of FASD-related diagnoses that can be attributed to alcohol use during
      pregnancy were estimated by a systematic review. The incidence was measured as
      the number of new cases per 1000 births. The prevalence was measured as the
      number of cases per 1000 population in 2012. RESULTS: Annually, 739 to 1884
      people were born with FASD in Alberta establishing an incidence of 14.2 to 43.8
      per 1000 births, depending on the length of follow-up. There were about 46,000
      people living with FASD in Alberta 2012, including 6,000 FAS cases and 40,000
      FASD-related cases. The prevalence of FASD was 11.7 (range 8.2 to 15.1) per 1000
      population. The incidence and prevalence varied greatly by sex and age group.
      Generally, male and younger outnumbered female and older. CONCLUSION: This study
      suggests new incidence and prevalence of FASD, which are higher than what has
      been commonly used (1%), and its variations among sex and age groups.

PMID- 25381630
TI  - Respiratory sinus arrhythmia stabilizes mean arterial blood pressure at high
      frequency interval in healthy humans.
AB  - PURPOSE: Arterial blood pressure variations are an independent risk factor for
      end organ failure. Respiratory sinus arrhythmia (RSA) is a sign of a healthy
      cardiovascular system. However, whether RSA counteracts arterial blood pressure
      variations during the respiratory cycle remains controversial. We restricted
      normal RSA with non-invasive intermittent positive pressure ventilation (IPPV) to
      test the hypothesis that RSA normally functions to stabilize mean arterial blood
      pressure. METHODS: Ten young volunteers were investigated during metronome-paced
      breathing and IPPV. Heart rate (ECG), mean arterial blood pressure and left
      stroke volume (finger arterial pressure curve) and right stroke volume (pulsed
      ultrasound Doppler) were recorded, while systemic and pulmonary blood flow were
      calculated beat-by-beat. Respiratory variations (high-frequency power, 0.15-0.40
      Hz) in cardiovascular variables were estimated by spectral analysis. Phase angles
      and correlation were calculated by cross-spectral analysis. RESULTS: The
      magnitude of RSA was reduced from 4.9 bpm(2) (95% CI 3.0, 6.2) during metronome
      breathing to 2.8 bpm(2) (95% CI 1.1, 5.0) during IPPV (p = 0.03). Variations in
      mean arterial blood pressure were greater (2.3 mmHg(2) (95% CI 1.4, 3.9) during
      IPPV than during metronome breathing (1.0 mmHg(2) [95% CI 0.7, 1.3]) (p = 0.014).
      Respiratory variations in right and left stroke volumes were inversely related in
      the respiratory cycle during both metronome breathing and IPPV. CONCLUSIONS: RSA
      magnitude is lower and mean arterial blood pressure variability is greater during
      IPPV than during metronome breathing. We conclude that in healthy humans, RSA
      stabilizes mean arterial blood pressure at respiratory frequency.

PMID- 25381629
TI  - Effects of tadalafil administration on plasma markers of exercise-induced muscle
      damage, IL6 and antioxidant status capacity.
AB  - INTRODUCTION: Physical exercise is associated with enhanced production of
      reactive oxygen species, which if uncontrolled can result in tissue injury.
      Phosphodiesterase type 5 inhibitors (PDE5i) exhibit protective effect against
      oxidative stress, both in animals and healthy/unhealthy humans. However, the
      effect of a chronic administration of PDE5i, particularly combined with physical
      exercise, has never been investigated. PURPOSE: The present study was designed to
      evaluate the effect of the long-acting PDE5i tadalafil on oxidative status and
      muscle damage after exhaustive exercise in healthy males included in a double
      blind crossover trial. HYPOTHESIS: Tadalafil, having a putative antioxidant
      activity, may reduce oxidative damage after strenuous exercise. METHODS: Each
      volunteer randomly received two tablets of placebo or tadalafil (20 mg/day) with
      36 h of interval before performing exhaustive exercise. After 2 weeks of washout,
      the volunteers were crossed over. Blood samples were collected immediately before
      exercise, immediately after, and during recovery (15, 30, 60 min). Plasma total
      antioxidant status, glutathione homeostasis (GSH/GSSG), malondialdehyde (MDA),
      protein carbonyls, creatine kinase (CK), lactate dehydrogenase (LDH) and the
      inflammatory cytokine interleukin 6 were assessed. RESULTS: Tadalafil
      administration per se affected redox homeostasis (GSH/GSSG -36%; p < 0.05),
      cellular (CK +75% and LDH +36%; p < 0.05) and oxidative damage (MDA +41% and
      protein carbonyls +50%; p < 0.05) markers. The exhaustive exercise increased all
      the above-reported biochemical parameters, with subjects from the tadalafil group
      showing significantly higher values with respect to the placebo group.
      CONCLUSIONS: A prolonged exposure to tadalafil decreases antioxidant capacity at
      resting condition, therefore making subjects more susceptible to the oxidative
      stress induced by an exhaustive bout of exercise.

PMID- 25381631
TI  - Diversity of actinomycetes isolated from subseafloor sediments after prolonged
      low-temperature storage.
AB  - Subseafloor sediments present an untapped source of novel bacterial species with
      industrially important bioactivities. Subseafloor core samples collected during
      the Integrated Ocean Drilling Program Expeditions 315, 316, and 331 and stored in
      Kochi Core Center at -80  degrees C for 1 to 4 years were used for cultivation
      based study of viable actinomycetes. In total, more than 100 actinomycete-like
      colonies were isolated from two deep-frozen subseafloor sediment samples.
      Isolated actinomycetes showed close similarity to known Actinotalea, Dietzia,
      Gordonia, Isoptericola, Microbacterium, Nocardia, Rhodococcus, Pseudonocardia,
      Streptomyces, and Tsukamurella species and were halotolerant. Bioactivity assays
      revealed that two of the isolates were producing potent antibacterial compound(s)
      and one isolate was having antifungal activity. Our study demonstrated that deep
      frozen subseafloor core samples could be a potential source of viable
      actinomycetes, which may be used in drug discovery.

PMID- 25381632
TI  - Stem cell therapy for GI neuromuscular disorders.
AB  - The enteric nervous system is the intrinsic innervation of the gut. Several
      neuromuscular disorders affect the neurons and glia of the enteric nervous system
      adversely, resulting in disruptions in gastrointestinal motility and function.
      Pharmacological interventions to remedy gastrointestinal function do not address
      the underlying cause of dysmotility arising from lost, absent, or damaged enteric
      neuroglial circuitry. Cell-based therapies have gained traction in the past
      decade, following the discovery of several adult stem cell niches in the human
      body. Adult neural stem cells can be isolated from the postnatal and adult
      intestine using minimally invasive biopsies. These stem cells retain the ability
      to differentiate into several functional classes of enteric neurons and enteric
      glia. Upon identification of these cells, several groups have also established
      that transplantation of these cells into aganglionic or dysganglionic intestine
      rescues gastrointestinal motility and function. This chapter highlights key
      studies performed in the field of stem cell transplantation therapies that are
      targeted towards the remedy of gastrointestinal motility and function. 

PMID- 25381633
TI  - Protective effect of KI in mtDNA in porcine thyroid: comparison with KIO3 and
      nDNA.
AB  - PURPOSE: Iodine, bivalent iron (Fe2+), and hydrogen peroxide (H2O2), all
      significantly affecting the red-ox balance, are required for thyroid hormone
      synthesis. Intracellular iodine excess (>=10-3 M) transiently blocks thyroid
      hormonogenesis (an adaptive mechanism called Wolff-Chaikoff effect). The aim of
      the study was to evaluate the effects of iodine, used as potassium iodide (KI) or
      potassium iodate (KIO3), in concentrations corresponding to those typical for
      Wolff-Chaikoff effect, on the level of oxidative damage to nuclear DNA (nDNA) and
      mitochondrial DNA (mtDNA) isolated from porcine thyroid under basal conditions
      and in the presence of Fenton reaction (Fe2++H2O2 -> Fe3++(.)OH + OH-)
      substrates. METHODS: Thyroid nDNA and mtDNA were incubated in the presence of
      either KI or KIO3 (2.5-50 mM), without/with FeSO4 (30 uM) + H2O2 (0.5 mM). Index
      of DNA damage, i.e., 8-oxo-7,8-dihydro-2'-deoxyguanosine, was measured by HPLC.
      RESULTS: Neither KI nor KIO3 increased the basal level of 8-oxodG in both nDNA
      and mtDNA. KI-in all used concentrations-completely prevented the damaging effect
      of Fenton reaction substrates in mtDNA, and it partially prevented this damage in
      nDNA. KIO3 partially prevented Fe2++H2O2-induced oxidative damage in both DNA
      only in its highest used concentrations (>=25 mM). CONCLUSIONS: Without
      additional prooxidative abuse, both iodine compounds, i.e., KI and KIO3, seem to
      be safe in terms of their potential oxidative damage to DNA in the thyroid. The
      superiority of KI over KIO3 relies on its stronger protective effects against
      oxidative damage to mtDNA, which constitutes an argument for its preferential
      utility in iodine prophylaxis.

PMID- 25381634
TI  - Radiological characteristics, histological features and clinical outcomes of lung
      cancer patients with coexistent idiopathic pulmonary fibrosis.
AB  - INTRODUCTION: Despite advances in diagnosis and management, the outcomes for both
      lung cancer and idiopathic pulmonary fibrosis (IPF) are still unfavourable. The
      pathophysiology and outcomes for patients with concomitant lung cancer and IPF
      remains unclear. METHODOLOGY: A retrospective analysis was performed of all
      patients presenting with concomitant IPF and lung cancer to our centre over a 3
      year period. Patients with connective tissue disease, asbestos exposure,
      sarcoidosis, previous thoracic radiation, radiological evidence of fibrosis but
      no histological confirmation of lung cancer, or the use of medications known to
      cause pulmonary fibrosis were excluded. We describe clinical, radiological and
      pathological characteristics of this group. We also report the response to
      standardized lung cancer therapy in this cohort. RESULTS: Of 637 lung cancer
      patients, 34 were identified with concomitant IPF (5.3 %) and all were smokers.
      85 % had non-small cell lung cancer, 41 % were squamous cell cancers. The
      majority of tumours were located in the lower lobes, peripheral and present in an
      area of honeycombing. Despite the fact that approximately 2/3rds of the patients
      had localised or locally advanced lung cancer, the outcome of therapy for lung
      cancer was extremely poor regardless of tumour stage or severity of IPF.
      CONCLUSIONS: At our centre, 1/20 patients with lung cancer have concomitant IPF.
      The majority of these tumours are small in size, peripheral in location and
      squamous cell carcinoma; in an area of honey combing. The outcome for concomitant
      lung cancer and IPF regardless of stage or therapy is poor.

PMID- 25381635
TI  - Understanding the Mechanisms Underlying Gambling Behaviour and Sleep.
AB  - Problem gambling and sleep difficulty threaten health. Using the basis of self
      regulatory theory, potential mechanisms for these problems were investigated.
      Fifty-nine treatment-seeking gamblers completed the Pittsburgh Sleep Quality
      Index (sleep difficulty), the Sleep Hygiene Index (negative sleep habits), the
      Problem Gambling Severity Index and measures of self-regulatory capacity and
      arousability with data entered into regression analyses. Results supported the
      relationship between problem gambling and greater sleep difficulty (beta = .18, t
      = 3.22, p < .01). Self-regulatory capacity mediated the relationship between
      problem gambling and sleep difficulty (R (2) change = .15, F(2, 57) = 12.14, beta
      = -.45, t = -3.45, p < .001) as well as between problem gambling and negative
      sleep habits; R (2) change = .17, F(2, 57) = 13.57, beta = -.28, t = -3.76, p <
      .001. Arousability predicted sleep difficulty (beta = .15, t = 3.07, p < .01) and
      negative sleep habits (beta = .40, t = 5.40, p < .01) but showed no relationship
      with problem gambling (r = .09, ns). Self-regulatory capacity represents an
      important mediator of the relationship between problem gambling and sleep-related
      behaviour and if targeted could reduce behavioural threats to health.

PMID- 25381636
TI  - Nicotine-induced upregulation of VCAM-1, MMP-2, and MMP-9 through the alpha7
      nAChR-JNK pathway in RAW264.7 and MOVAS cells.
AB  - The ability of nicotine to induce aortic aneurysms has been shown in animal
      models; however, its underlying mechanisms remain elusive. In the present
      experiment, both the RAW264.7 and MOVAS cell lines were employed to examine the
      nicotine-induced modulation of VCAM-1, MMP-2, and MMP-9 expressions in
      macrophages and vascular smooth muscle cells. Our results showed that nicotine
      concentrations of both 0.5 and 5 ng/ml induced VCAM-1, MMP-2, and MMP-9
      upregulation, while a concentration of 50 ng/ml had a slight inhibitory effect
      and a concentration of 500 ng/ml showed a significant inhibitory effect. When
      cells were pretreated with either SP600125 (JNK inhibitor) or PNU-282987 (alpha7
      nAChR agonist) prior to nicotine exposure, the nicotine-induced upregulation of
      VCAM-1, MMP-2, MMP-9, and p-JNK was suppressed, with a joint treatment producing
      a more significant inhibitory effect. Moreover, PNU-282987 had a comparable
      inhibitory effect on VCAM-1, MMP-2, and MMP-9 expressions and JNK activation via
      phosphorylation as did SP600125. In conclusion, nicotine-induced VCAM-1, MMP-2,
      and MMP-9 expressions occur in a dose-dependent fashion in both of the cell lines
      tested. Furthermore, the nicotine exposure equivalent to plasma levels found in
      regular smokers can augment VCAM-1, MMP-2, and MMP-9 expressions through the
      alpha7-nAChR-JNK pathway. 

PMID- 25381637
TI  - Sphingosine 1-phosphate lyase inhibition by 2-acetyl-4
      (tetrahydroxybutyl)imidazole (THI) under conditions of vitamin B6 deficiency.
AB  - Caramel food colorant 2-acetyl-4-(tetrahydroxybutyl)imidazole (THI) causes
      lymphopenia in animals through sphingosine 1-phosphate lyase (SPL) inhibition.
      However, this mechanism of action is partly still controversial because THI did
      not inhibit SPL in vitro either in cell-free or in cell-based systems. It is
      thought that the in vitro experimental conditions which have been used so far
      were not suitable for the evaluation of SPL inhibition, especially in case of
      cell-based experiments. We speculated that the key factor might be the coenzyme
      pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 (VB6), because media
      used in cell-based assays usually contain an excess amount of VB6 which leads to
      the activation of SPL. By the use of VB6-deficient culture medium, we could
      regulate apo- (without PLP) and holo- (with PLP) SPL enzyme in cultured cells,
      resulting in the successful detection of SPL inhibition by THI. Although the
      observed inhibitory effect was not as strong as that of 4-deoxypyridoxine (a VB6
      analog SPL inhibitor), these findings may be useful for further understanding the
      mechanism of action of THI. 

PMID- 25381638
TI  - Treatment strategies and long-term outcomes for primary intramedullary spinal
      germinomas: an institutional experience.
AB  - Primary intramedullary germinomas are very rare tumors in the spinal cord. This
      study presented a series of 11 patients with histologically proven primary
      intramedullary spinal germinomas. Their clinical and radiological findings,
      treatment records and long-term outcomes were reviewed. There were four male and
      seven female patients with a mean age of 27.1 years. Because germ cell tumors
      were suspected by frozen-section biopsy, gross total resection was unattempted.
      Partial resection was performed in four cases, while biopsy was performed in
      seven cases. Postoperatively, carboplatin and etoposide chemotherapy combined
      with low dose radiotherapy (30.6 Gy) to local spine was performed in seven cases,
      followed by radiotherapy alone (40 Gy) in four cases. All 11 patients had a
      complete response to either combination treatment or single radiotherapy, and the
      mass effect on the spinal cord vanished. The mean follow-up period was 75.4
      months. At the last follow-up, the symptoms were improved in 10 cases and the
      current status of one patient was unchanged. The postoperative follow-up magnetic
      resonance imaging showed no recurrence or dissemination in any of the patients.
      Primary intramedullary germinomas are amenable to adjuvant radiochemotherapy and
      low dose radiation with etoposide and carboplatin chemotherapy is recommended.
      When combination therapy cannot be performed, relatively high doses of
      radiotherapy are advised, and radiation to the craniospinal axis may be
      unnecessary. A good clinical outcome after combination therapy or radiotherapy
      alone can be expected, and the risk of long-term recurrence and dissemination is
      low.

PMID- 25381639
TI  - Zinc down regulates Apaf-1-dependent Bax/Bcl-2 mediated caspases activation
      during aluminium induced neurotoxicity.
AB  - Aluminium (Al), a ubiquitous element in nature is associated with the onset of
      Alzheimer's disease. On the other hand, zinc (Zn) is an essential trace element
      that regulates large number of physiological processes in the human body. The
      present study was conducted to explore the role of zinc, if any, in regulating
      apoptotic machinery during Al induced neurodegeneration in rat. Male sprague
      dawley rats weighing 140-160 g were divided into four different groups viz:
      Normal control, Al treated (100 mg/kg b.wt./day), Zn treated (227 mg/l) and
      combined Al and Zn treated. All the treatments were carried out for a total
      duration of 8 weeks. Al treatment resulted in a significant increase in the
      protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17),
      caspase 8, caspase 6, caspase 7 but decreased the Bcl-2 in both the cerebrum and
      cerebellum. However, Zn supplementation to Al treated rats resulted in a
      reduction in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9,
      caspase 3 (p17), caspase 8, caspase 6 and caspase 7 whereas it elevated the Bcl-2
      in both the regions. Further, gene expressions of caspase 3 and caspase 9 were
      also found to be elevated after Al treatment, which however were reduced
      following Zn co-treatment. The electron-microscopic analysis of brain revealed
      that Al intoxication resulted in a number of degenerative signs at
      ultrastructural level, which were appreciably improved upon Zn supplementation.
      The present study suggests that Zn provides protection against Al induced
      neurotoxicity by triggering anti-apoptotic machinery.

PMID- 25381641
TI  - NeuralAct: A Tool to Visualize Electrocortical (ECoG) Activity on a Three
      Dimensional Model of the Cortex.
AB  - Electrocorticography (ECoG) records neural signals directly from the surface of
      the cortex. Due to its high temporal and favorable spatial resolution, ECoG has
      emerged as a valuable new tool in acquiring cortical activity in cognitive and
      systems neuroscience. Many studies using ECoG visualized topographies of cortical
      activity or statistical tests on a three-dimensional model of the cortex, but a
      dedicated tool for this function has not yet been described. In this paper, we
      describe the NeuralAct package that serves this purpose. This package takes as
      input the 3D coordinates of the recording sensors, a cortical model in the same
      coordinate system (e.g., Talairach), and the activation data to be visualized at
      each sensor. It then aligns the sensor coordinates with the cortical model,
      convolves the activation data with a spatial kernel, and renders the resulting
      activations in color on the cortical model. The NeuralAct package can plot
      cortical activations of an individual subject as well as activations averaged
      over subjects. It is capable to render single images as well as sequences of
      images. The software runs under Matlab and is stable and robust. We here provide
      the tool and describe its visualization capabilities and procedures. The provided
      package contains thoroughly documented code and includes a simple demo that
      guides the researcher through the functionality of the tool. 

PMID- 25381642
TI  - EZH2, the moderator in the discussion between methyltransferases at histone H3?

PMID- 25381640
TI  - Intracardiac thrombus in Behcet's disease: four new cases and a comprehensive
      literature review.
AB  - Behcet's disease (BD) is a multisystem inflammatory disorder. Intracardiac
      thrombus formation (ICTF) is an uncommon but important complication of BD. To
      highlight recent insights into this disease, we aimed to review ICTF and other
      systemic involvements associated with ICTF in BD. We conducted a comprehensive
      review of the relevant literature in MEDLINE and EMBASE from 1966 to 2014 to
      analyze cumulated data about ICTF in BD. We aimed to evaluate 93 cases of BD with
      ICT (group 1), four of which have been recently identified and have not been
      discussed in the relevant literature yet, and to compare the frequency of
      pulmonary, venous and arterial involvements in group 1 and general Behcet
      population (group 2). The right heart was the most common site of ICTF in group
      1. Pulmonary involvement, venous involvement (especially venous thrombosis) and
      arterial involvement were more frequent in group 1 than in group 2 (56 vs. 0.7 %,
      42 vs. 10 % and 38 vs. 0.8 %, respectively, p < 0.0001). The diagnosis of BD
      should be considered if a patient presents with a mass in the right-sided cardiac
      chambers, even in the absence of the characteristic clinical manifestations of
      the illness. This approach is particularly applicable if the patient is a young
      man from the Mediterranean basin or the Middle East. All Behcet patients with
      ICTF must be investigated with thoracic computed tomography for pulmonary and
      arterial involvements and lower extremity venous Doppler ultrasonography for
      venous thrombosis, regardless of whether they are symptomatic for these systems. 

PMID- 25381643
TI  - Genome-wide linkage analysis and tumoral characterization reveal heterogeneity in
      familial colorectal cancer type X.
AB  - BACKGROUND: Familial colorectal cancer type X (FCCTX) fulfils clinical criteria
      defining Lynch syndrome (LS), but is not related to germline mutations in DNA
      mismatch-repair genes. Its aetiology remains unexplained and there is little
      evidence of involvement of the common colorectal carcinogenetic pathways. We
      aimed to identify susceptibility loci and gain insights into carcinogenic
      pathways involved FCCTX tumour development. METHODS: We performed a linkage
      analysis in 22 FCCTX families. We also constructed a tissue microarray in order
      to define an immunohistochemical (IHC) profile for FCCTX tumours (N = 27) by
      comparing them to three other types of colorectal tumors: LS (N = 18), stable
      early-onset (N = 31) and other sporadic disease (N = 80). Additionally, we
      screened for BRAF/KRAS mutations and determined CpG island methylator phenotype
      (CIMP) status for all FCCTX tumours. RESULTS: We found suggestive evidence of
      linkage at four chromosomal regions; 2p24.3, 4q13.1, 4q31.21 and 12q21.2-q21.31.
      We screened genes in 12q21 and ruled out the implication of RASSF9 and NTS, good
      candidates due to their potential involvement in carcinogenesis and colorectal
      epithelium development. Based on IHC profiles FCCTX tumours did not form a
      single, exclusive cluster. They were clearly different from LS, but very similar
      to stable early onset tumours. The CIMP and chromosomal instability pathways were
      implicated in one-third and one-quarter of FCCTX cases, respectively. The
      remaining cases did not have alterations in any known carcinogenic pathways.
      CONCLUSIONS: Our results highlight the heterogeneity of FCCTX tumours and call
      into question the utility of using only clinical criteria to identify FCCTX
      cases.

PMID- 25381644
TI  - Reliability and validity of the Chinese version of the short form of the Dentine
      Hypersensitivity Experience Questionnaire (DHEQ-15).
AB  - OBJECTIVES: The aim of this study was to validate the short form of the Dentine
      Hypersensitivity Experience Questionnaire (DHEQ-15) in Chinese patients with
      dentine hypersensitivity (DH). METHODS: In total, 200 patients with DH were
      recruited to complete the questionnaire. The reliability of the DHEQ-15 was
      evaluated using internal consistency and test-retest methods. The exploratory
      factor analysis (EFA) was conducted to identify domains of the DHEQ-15.
      Convergent validity was determined by analyzing the correlation between DHEQ-15
      subscale scores and the global rating of oral health question. RESULTS:
      Cronbach's alpha value (internal reliability) for the total DHEQ-15 score was
      0.934 (higher to the original DHEQ-15' 0.924), and the intraclass correlation
      coefficient value (test-retest reliability) was 0.894 (lower to the original DHEQ
      15' 0.939). The EFA identified three components with eigenvalues >1, explaining
      53.0, 17.1, and 12.3% of the variance, respectively, accounting for a total of
      82.4% of the variance. The three components named 'restrictions' (three items),
      'changes in eating habits' (six items), and 'emotions and identity' (six items).
      In terms of convergent validity, the DHEQ-15 subscale was significant highly
      negatively correlated to the global oral health rating. CONCLUSIONS: The results
      provide initial evidence that the DHEQ-15 can be properly used for assessment of
      patients with DH in China.

PMID- 25381645
TI  - Electrophysiological study 6 months after EpicorTM high-intensity focused
      ultrasound atrial fibrillation ablation.
AB  - PURPOSE: Little is presently known about the outcome of atrial lesions performed
      with high-intensity focused ultrasound (HIFU) for atrial fibrillation ablation.
      We aimed to assess endocardial atrial lesions 6 months after epicardial HIFU
      ablation (Epicor(TM)) and to evaluate the benefit of a combined ablation
      approach. METHODS: Thirty patients (21 males, mean age 68 +/- 12 years old)
      undergoing HIFU atrial fibrillation ablation during cardiac surgery were
      enrolled. Electrophysiological study (EPS) was performed 6 months after HIFU
      ablation, and endovascular radiofrequency was delivered in case of conduction
      gaps. Patients were followed up for at least 6 months after the EPS. RESULTS: At
      EPS, ten patients (38 %) had achieved complete or near-complete "box" isolation
      and four (15 %) had no visible lesion. Using this technology, freedom from
      symptomatic atrial arrhythmia at 6 months was 60 % (n = 18/30) (64 % for
      paroxysmal and 56 % for persistent subgroups) improving to 81 % (n = 21/26) (90 %
      for paroxysmal and 73 % for persistent subgroups) at 12 months after a
      facultative percutaneous endocardial approach was performed. Using an UltraCinch
      device sized below 10 improved the rate of complete lesion as assessed 6 months
      after surgery (58 % of complete or near-complete box isolation with UltraCinch
      device <10 vs 21 % when >=11; p = 0.05). CONCLUSION: Six months after HIFU
      ablation, only 38 % of the patients had complete or near-complete box isolation,
      and the recurrence rate of symptomatic atrial arrhythmia was 40 %. The latter was
      reduced to 19 % 6 months after complementary percutaneous approach.

PMID- 25381646
TI  - Irreversible electropermeabilization of the human pathogen Candida albicans: an
      in-vitro experimental study.
AB  - Pathogenic fungi cause many life-threatening infections, especially among
      individuals with immune system dysfunction. The antifungal drugs commonly used to
      suppress fungal pathogens can result in long-lasting and toxic therapy. In this
      work, irreversible electropermeabilization was used to investigate the dynamics
      of the decrease in Candida albicans colony vitality after application of a pulsed
      electric field (PEF) and use of antifungal drugs. The fungi were subjected to
      single 250-us to 2-ms (0.5-2.5 kV/cm) pulses or repeated short 5-us pulses, and
      efficacy was compared. It was shown that electropermeabilization combined with
      antifungal agents results in rapid and more effective treatment, eliminating more
      than 90% of C. albicans colony-forming units in a single procedure, which is
      advantageous in biomedicine. It was also observed that, because of application of
      PEF and use of the antifungal agents, the Candida cells form cell aggregates and
      average live cell size is reduced by as much as 53%.

PMID- 25381647
TI  - Savings in Medical Expenditures Associated with Reductions in Body Mass Index
      Among US Adults with Obesity, by Diabetes Status.
AB  - BACKGROUND: The prevalence of obesity has more than doubled in the USA in the
      past 30 years. Obesity is a significant risk factor for diabetes, cardiovascular
      disease, and other clinically significant co-morbidities. This paper estimates
      the medical care cost savings that can be achieved from a given amount of weight
      loss by people with different starting values of body mass index (BMI), for those
      with and without diabetes. This information is an important input into analyses
      of the cost effectiveness of obesity treatments and prevention programs. METHODS:
      Two-part models of instrumental variables were estimated using data from the
      Medical Expenditure Panel Survey (MEPS) for 2000-2010. Models were estimated for
      all adults as well as separately for those with and without diabetes. We
      calculated the causal impact of changes in BMI on medical care expenditures, cost
      savings for specific changes in BMI (5, 10, 15, and 20 %) from starting BMI
      levels ranging from 30 to 45 kg/m(2), as well as the total excess medical care
      expenditures caused by obesity. RESULTS: In the USA, adult obesity raised annual
      medical care costs by $US3,508 per obese individual, for a nationwide total of
      $US315.8 billion (year 2010 values). However, the relationship of medical care
      costs over BMI is J-shaped; costs rise exponentially in the range of class 2 and
      3 obesity (BMI >=35). The heavier the obese individual, the greater the reduction
      in medical care costs associated with a given percent reduction in BMI. Medical
      care expenditures are higher, and rise more with BMI, among individuals with
      diabetes than among those without diabetes. CONCLUSIONS: The savings from a given
      percent reduction in BMI are greater the heavier the obese individual, and are
      greater for those with diabetes than for those without diabetes. The results
      provide health insurers, employers, government agencies, and health economists
      with accurate estimates of the change in medical care expenditures resulting from
      weight loss, which is important information for calculating the cost
      effectiveness of interventions to prevent and treat obesity.

PMID- 25381648
TI  - Ethical Tensions in the Pain Management of an End-Stage Cancer Patient with
      Evidence of Opioid Medication Diversion.
AB  - At the end of life, pain management is commonly a fundamental part of the
      treatment plan for patients where curative measures are no longer possible.
      However, the increased recognition of opioid diversion for secondary gain coupled
      with efforts to treat patients in the home environment towards the end of life
      creates the potential for ethical dilemmas in the palliative care management of
      terminal patients in need of continuous pain management. We present the case of
      an end-stage patient with rectal cancer who required a continuous residential
      narcotic infusion of fentanyl for pain control due to metastatic disease. His
      functional status was such that he had poor oral intake and ability to perform
      other activities of daily living, but was able to live at home with health agency
      nursing care. The patient presented to this institution with a highly suspect
      history of having lost his fentanyl infusion in a residential accident and asking
      for a refill to continue home therapy. The treating physicians had concerns of
      diversion of the infusion medication by caregivers and were reluctant to continue
      the therapeutic relationship with the patient. This case exemplifies the tension
      that can exist between wanting to continue with palliative care management of an
      end-stage patient and the fear of providers when confronted by evidence of
      potential diversion of opioid analgesic medications. We elucidate how an ethical
      framework based on a combination of virtue and narrative/relationship theories
      with reference to proportionality can guide physicians to a pragmatic resolution
      of these difficult situations. 

PMID- 25381649
TI  - Farewell to oligoastrocytoma: response to letters.

PMID- 25381650
TI  - Elucidation of fluoranthene degradative characteristics in a newly isolated
      Achromobacter xylosoxidans DN002.
AB  - Strain DN002 isolated from petroleum-contaminated soil was identified as
      Achromobacter xylosoxidans based on morphological and biochemical properties and
      16S rRNA phylogeny, and investigated for its potential to utilize numerous
      polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene and pyrene as sole
      carbon and energy resource. Biodegradation studies showed that 500 mg(.)l(
      1)fluranthene was degraded to 35.6 +/- 0.3 mg(.)l(-1) by DN002 after 14 days
      incubation. During fluoranthene biodegradation, catechol 2,3 dioxygenase (C23O)
      activity was augmented 1.5 times more than catechol 1,2 dioxygenase (C12O), which
      indicated that C23O played a major role in fluoranthene degradation by DN002.
      Protein profiles were examined by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis and two-dimensional electrophoresis then analyzed by mass
      spectrometry induced by fluoranthene; a molecular mass range of 18 ~ 66 kDa
      proteins were found upregulated compared with the uninduced control sample,
      including multiple isoenzymes of beta-oxidation and dehydrogenases as well as
      dioxygenases. Besides, some new proteins, i.e., dihydrolipoamide
      succinyltransferase and aldehyde dehydrogenase family proteins and isocitrate
      lyase were also synthesized.

PMID- 25381651
TI  - Three-dimensional analyses of aging-induced alterations in facial shape: a
      longitudinal study of 171 Japanese males.
AB  - We sought to generate data to facilitate forensic facial comparisons.
      Specifically, we conducted a longitudinal study of alterations in face shape
      induced by aging. We obtained two three-dimensional facial shape measurements in
      171 Japanese males at intervals of approximately 10 years. With this data, we
      created a homologous model consisting of 10,741 data points for each face based
      on 33 anatomical landmarks. We averaged the movements of corresponding data
      points between the two homologous models for each individual and used this data
      to predict up to 30 years of face aging in an average Japanese male. We clearly
      identified aging-induced shape changes, such as drooping and denting of the
      facial folds, drooping of the upper lip, and projection of the lower eyelid, in
      the virtually aged model. A quantitative comparison of aging-induced shape
      alterations among three age groups (individuals in their 20's, 30's, and 40-50's)
      showed that these alterations accelerated more quickly as age increased. Using
      our predictive model, we conducted a preliminary study focused on facial shape
      alterations induced by reductions in body weight. Our findings indicated that our
      proposed method would also be valid for this purpose. 

PMID- 25381652
TI  - Good Vibrations: Successful Endoscopic Electrohydraulic Lithotripsy for
      Bouveret's Syndrome.

PMID- 25381653
TI  - The influence of age and mild cognitive impairment on associative memory
      performance and underlying brain networks.
AB  - Associative memory is essential to everyday activities, such as the binding of
      faces and corresponding names to form single bits of information. However, this
      ability often becomes impaired with increasing age. The most important neural
      substrate of associative memory is the hippocampus, a structure crucially
      implicated in the pathogenesis of Alzheimer's disease (AD). The main aim of this
      study was to compare neural correlates of associative memory in healthy aging and
      mild cognitive impairment (MCI), an at-risk state for AD. We used fMRI to
      investigate differences in brain activation and connectivity between young
      controls (n = 20), elderly controls (n = 32) and MCI patients (n = 21) during
      associative memory retrieval. We observed lower hippocampal activation in MCI
      patients than control groups during a face-name recognition task, and the
      magnitude of this decrement was correlated with lower associative memory
      performance. Further, increased activation in precentral regions in all older
      adults indicated a stronger involvement of the task positive network (TPN) with
      age. Finally, functional connectivity analysis revealed a stronger link of
      hippocampal and striatal components in older adults in comparison to young
      controls, regardless of memory impairment. In elderly controls, this went hand-in
      hand with a stronger activation of striatal areas. Increased TPN activation may
      be linked to greater reliance on cognitive control in both older groups, while
      increased functional connectivity between the hippocampus and the striatum may
      suggest dedifferentiation, especially in elderly controls. 

PMID- 25381654
TI  - Selective forces on origin, adaptation and reduction of tympanal ears in insects.
AB  - Insect ears evolved many times independently. As a consequence, a striking
      diversity exists in the location, construction and behavioural implementation of
      ears. In this review, we first summarise what is known about the evolutionary
      origin of ears and the presumed precursor organs in the various insect groups.
      Thereafter, we focus on selective forces for making and keeping an ear: we
      discuss detecting and localising predators and conspecifics, including
      establishing new "private" channels for intraspecific communication. More
      advanced aspects involve judging the distance of conspecifics, or assessing
      individual quality from songs which makes auditory processing a means for
      exerting sexual selection on mating partners. We try to identify negative
      selective forces, mainly in the context of energy expenditure for developing and
      keeping an ear, but also in conjunction with acoustic communication, which
      incorporates risks like eavesdropping by predators and parasitoids. We then
      discuss balancing pressures, which might oppose optimising an ear for a specific
      task (when it serves different functions, for example). Subsequently, we describe
      various scenarios that might have led to a reduction or complete loss of ears in
      evolution. Finally, we describe cases of sex differences in ears and potential
      reasons for their appearance. 

PMID- 25381656
TI  - [Pre-conception sex selection].
AB  - According to Article 14 of the Oviedo Convention on Human Rights and Biomedicine
      of the Council of Europe, the use of techniques of medically assisted procreation
      shall not be allowed for the purpose of choosing the sex of a future child,
      unless serious hereditary sex-related disease is to be avoided. In Israel and the
      United States of America, pre-conception sex selection for the purpose of family
      balancing is legal. The European health culture does not regard reproductive
      justice as part of social justice. From this aspect, the situation is very
      similar in China and India. Reproductive liberty is opposed by the Catholic
      Church, too. According to the Catholic Church, medical grounds may not justify
      pre-conception sex selection, though being bioethically less harmful than family
      balancing for social reasons. In Hungary, according to Section 170 of the
      Criminal Code, pre-conception sex selection for the purpose of family balancing
      constitutes a crime. At present, the Hungarian legislation is in full harmony
      with the Oviedo Convention, enacted in Hungary in 2002.

PMID- 25381657
TI  - [Challenges of the modern antibody diagnostics in kidney transplantation].
AB  - Overcoming antibody mediated rejection is of increasing interest in the field of
      transplantation immunology. The recipient's antibodies against the graft human
      leukocyte antigens are responsible for antibody mediated graft injury.
      Introduction of the solid phase immunoassay technology radically changed the
      monitoring practice of antibodies against human leukocyte antigens, and this has
      consequences both for pretransplant and posttransplant phases, though our
      knowledge about the clinical interpretation of the detected antibodies is
      limited. This integrating review reports recommendations and algorithms regarding
      the management of kidney transplant patients. The detection of complement
      activation combined with the solid phase techniques is a promising new approach
      in antibody testing. The C4d and especially the more sensitive C1q methods have
      the potential to answer pivotal questions about the clinical relevance of
      antibodies. Answering the questions that the applied new methods raised and
      reviewing the recommendations are needed to remain up to date with this
      dynamically developing field.

PMID- 25381658
TI  - [Workload, work satisfaction and burnout among Hungarian female residents.
      Results of representative, online survey].
AB  - INTRODUCTION: Years of residency are the most challenging period of a medical
      carrier. AIM: The aim of this study was to analyze female residents' (n = 380)
      workload, work satisfaction and burnout. METHOD: Data in this representative,
      cross-sectional epidemiological study were obtained from online questionnaires
      completed by 380 female residents. For a wider interpretation of the data, male
      residents (n = 176) were included in the analysis as a control group. RESULTS:
      The average weakly work hours of female residents were 66 hours and 70% of them
      felt overloaded. The medium and high level personal accomplishment was 75.9%, the
      emotional exhaustion was 58% and the medium and high level of depersonalization
      subscale was 53%. Female residents were mostly dissatisfied with working
      conditions, financial status, and prestige of her work. Dissatisfaction with the
      Hungarian health system was about 80% and nearly a quarter of respondents were
      considering working abroad. CONCLUSIONS: Female residents represent the "critical
      mass" of the young doctors. Residents' well-being is an important indicator of
      the functioning and effectiveness of the health care system.

PMID- 25381655
TI  - Shedding new light on viral photosynthesis.
AB  - Viruses infecting the environmentally important marine cyanobacteria
      Prochlorococcus and Synechococcus encode 'auxiliary metabolic genes' (AMGs)
      involved in the light and dark reactions of photosynthesis. Here, we discuss
      progress on the inventory of such AMGs in the ever-increasing number of viral
      genome sequences as well as in metagenomic datasets. We contextualise these gene
      acquisitions with reference to a hypothesised fitness gain to the phage. We also
      report new evidence with regard to the sequence and predicted structural
      properties of viral petE genes encoding the soluble electron carrier
      plastocyanin. Viral copies of PetE exhibit extensive modifications to the N
      terminal signal peptide and possess several novel residues in a region
      responsible for interaction with redox partners. We also highlight potential
      knowledge gaps in this field and discuss future opportunities to discover novel
      phage-host interactions involved in the photosynthetic process. 

PMID- 25381659
TI  - [Summer course for Hungarian medical students, University of Aarhus, Denmark,
      1947].

PMID- 25381662
TI  - Lifestyle in the sperm: there is growing evidence that epigenetic marks can be
      inherited. But what is the nature of the information they store and over how many
      generations do they prevail?

PMID- 25381661
TI  - The extracellular matrix modulates the hallmarks of cancer.
AB  - The extracellular matrix regulates tissue development and homeostasis, and its
      dysregulation contributes to neoplastic progression. The extracellular matrix
      serves not only as the scaffold upon which tissues are organized but provides
      critical biochemical and biomechanical cues that direct cell growth, survival,
      migration and differentiation and modulate vascular development and immune
      function. Thus, while genetic modifications in tumor cells undoubtedly initiate
      and drive malignancy, cancer progresses within a dynamically evolving
      extracellular matrix that modulates virtually every behavioral facet of the tumor
      cells and cancer-associated stromal cells. Hanahan and Weinberg defined the
      hallmarks of cancer to encompass key biological capabilities that are acquired
      and essential for the development, growth and dissemination of all human cancers.
      These capabilities include sustained proliferation, evasion of growth
      suppression, death resistance, replicative immortality, induced angiogenesis,
      initiation of invasion, dysregulation of cellular energetics, avoidance of immune
      destruction and chronic inflammation. Here, we argue that biophysical and
      biochemical cues from the tumor-associated extracellular matrix influence each of
      these cancer hallmarks and are therefore critical for malignancy. We suggest that
      the success of cancer prevention and therapy programs requires an intimate
      understanding of the reciprocal feedback between the evolving extracellular
      matrix, the tumor cells and its cancer-associated cellular stroma. 

PMID- 25381663
TI  - The complexity and diversity of the Pathogenicity Locus in Clostridium difficile
      clade 5.
AB  - The symptoms of Clostridium difficile infection are caused by two closely related
      toxins, TcdA and TcdB, which are encoded by the 19.6 kb Pathogenicity Locus
      (PaLoc). The PaLoc is variably present among strains, and in this respect it
      resembles a mobile genetic element. The C. difficile population structure
      consists mainly of five phylogenetic clades designated 1-5. Certain genotypes of
      clade 5 are associated with recently emergent highly pathogenic strains causing
      human disease and animal infections. The aim of this study was to explore the
      evolutionary history of the PaLoc in C. difficile clade 5. Phylogenetic analyses
      and annotation of clade 5 PaLoc variants and adjoining genomic regions were
      undertaken using a representative collection of toxigenic and nontoxigenic
      strains. Comparison of the core genome and PaLoc phylogenies obtained for clade 5
      and representatives of the other clades identified two distinct PaLoc acquisition
      events, one involving a toxin A(+)B(+) PaLoc variant and the other an A(-)B(+)
      variant. Although the exact mechanism of each PaLoc acquisition is unclear,
      evidence of possible homologous recombination with other clades and between clade
      5 lineages was found within the PaLoc and adjacent regions. The generation of
      nontoxigenic variants by PaLoc loss via homologous recombination with PaLoc
      negative members of other clades was suggested by analysis of cdu2, although none
      is likely to have occurred recently. A variant of the putative holin gene present
      in the clade 5 A(-)B(+) PaLoc was likely acquired via allelic exchange with an
      unknown element. Fine-scale phylogenetic analysis of C. difficile clade 5
      revealed the extent of its genetic diversity, consistent with ancient
      evolutionary origins and a complex evolutionary history for the PaLoc. 

PMID- 25381664
TI  - Comparative genomics of the Campylobacter lari group.
AB  - The Campylobacter lari group is a phylogenetic clade within the epsilon
      subdivision of the Proteobacteria and is part of the thermotolerant Campylobacter
      spp., a division within the genus that includes the human pathogen Campylobacter
      jejuni. The C. lari group is currently composed of five species (C. lari,
      Campylobacter insulaenigrae, Campylobacter volucris, Campylobacter
      subantarcticus, and Campylobacter peloridis), as well as a group of strains
      termed the urease-positive thermophilic Campylobacter (UPTC) and other C. lari
      like strains. Here we present the complete genome sequences of 11 C. lari group
      strains, including the five C. lari group species, four UPTC strains, and a lari
      like strain isolated in this study. The genome of C. lari subsp. lari strain
      RM2100 was described previously. Analysis of the C. lari group genomes indicates
      that this group is highly related at the genome level. Furthermore, these genomes
      are strongly syntenic with minor rearrangements occurring only in 4 of the 12
      genomes studied. The C. lari group can be bifurcated, based on the flagella and
      flagellar modification genes. Genomic analysis of the UPTC strains indicated that
      these organisms are variable but highly similar, closely related to but distinct
      from C. lari. Additionally, the C. lari group contains multiple genes encoding
      hemagglutination domain proteins, which are either contingency genes or linked to
      conserved contingency genes. Many of the features identified in strain RM2100,
      such as major deficiencies in amino acid biosynthesis and energy metabolism, are
      conserved across all 12 genomes, suggesting that these common features may play a
      role in the association of the C. lari group with coastal environments and
      watersheds. 

PMID- 25381666
TI  - Co-culture system of human salivary gland epithelial cells and immune cells from
      primary Sjogren's syndrome patients: an in vitro approach to study the effects of
      Rituximab on the activation of the Raf-1/ERK1/2 pathway.
AB  - Primary Sjogren's syndrome (pSS) is a chronic autoimmune disorder of the exocrine
      glands with associated lymphocytic infiltrates in the affected glands. Dryness of
      the mouth and eyes results from involvement of the salivary and lacrimal glands.
      The efficacy of Rituximab (RTX) in pSS is still open to debate. This study
      delineates the signaling pathway involved in RTX-mediated down-regulation of pro
      inflammatory factors in a co-culture system of pSS salivary gland epithelial
      cells (SGEC) with syngeneic pSS B-lymphocytes. In addition, the effects of RTX on
      the activation of the Raf-1/ERK1/2 pathway in pSS SGEC co-cultured with syngeneic
      pSS T-lymphocytes were also investigated. This study demonstrated that RTX may
      interfere with the ERK1/2 pathway in a syngeneic co-culture of pSS SGEC with pSS
      B-lymphocytes, leading to decreased cytokine production by SGEC. These novel
      findings reveal that syngeneic co-culture of pSS SGEC with pSS B-lymphocytes
      leads to a down-regulation of Raf-1 in epithelial cells that adversely regulates
      the activity of the ERK1/2 pathway and determines a subsequent reduction of the
      release of pro-inflammatory factors. 

PMID- 25381667
TI  - Author's reply: To PMID 25141318.

PMID- 25381668
TI  - Author's reply: To PMID 25141313.

PMID- 25381665
TI  - The genome of the myxosporean Thelohanellus kitauei shows adaptations to nutrient
      acquisition within its fish host.
AB  - Members of Myxozoa, a parasitic metazoan taxon, have considerable detrimental
      effects on fish hosts and also have been associated with human food-borne
      illness. Little is known about their biology and metabolism. Analysis of the
      genome of Thelohanellus kitauei and comparative analysis with genomes of its two
      free-living cnidarian relatives revealed that T. kitauei has adapted to
      parasitism, as indicated by the streamlined metabolic repertoire and the tendency
      toward anabolism rather than catabolism. Thelohanellus kitauei mainly secretes
      proteases and protease inhibitors for nutrient digestion (parasite invasion), and
      depends on endocytosis (mainly low-density lipoprotein receptors-mediated type)
      and secondary carriers for nutrient absorption. Absence of both classic and
      complementary anaerobic pathways and gluconeogenesis, the lack of de novo
      synthesis and reduced activity in hydrolysis of fatty acids, amino acids, and
      nucleotides indicated that T. kitauei in this vertebrate host-parasite system has
      adapted to inhabit a physiological environment extremely rich in both oxygen and
      nutrients (especially glucose), which is consistent with its preferred parasitic
      site, that is, the host gut submucosa. Taking advantage of the genomic and
      transcriptomic information, 23 potential nutrition-related T. kitauei-specific
      chemotherapeutic targets were identified. This first genome sequence of a
      myxozoan will facilitate development of potential therapeutics for efficient
      control of myxozoan parasites and ultimately prevent myxozoan-induced fish-borne
      illnesses in humans. 

PMID- 25381669
TI  - Authors' reply.

PMID- 25381670
TI  - Author's reply: To PMID 25141314.

PMID- 25381671
TI  - Author's reply: To PMID 24918141.

PMID- 25381672
TI  - Author's reply: To PMID 25003670.

PMID- 25381677
TI  - Reynolds number dependency of an insect-based flapping wing.
AB  - Aerodynamic characteristics depending on Reynolds number (Re) ranges were studied
      to investigate the suitable design parameters of an insect-based micro air
      vehicle (MAV). The tests centered on the wing rotation timing and Re ranges, and
      were conducted to understand the lift augmentations and unsteady effects. A
      dynamically scaled-up flapping wing controlled by a pair of servos was installed
      underwater with a micro force/torque sensor. A high-speed camera and a laser
      sheet were also put in front of the water tank for the time-resolved digital
      particle image velocimetry (DPIV). The lift augmentations clearly appeared at low
      Re and were well reflected on the insect's flight range. In the case of the high
      Re, however, the peak standing for the wing-wake interaction was delayed, and the
      pitching-up rotation was not able to lead to another lift enhancement, i.e.,
      rotational lift. In such Re, the mean CL and the L/D of the advanced rotation
      were substantially decreased from those of the other rotations. The DPIV results
      at high Re well described turbulent characteristics such as the irregular,
      unstable, and high-intensity vortex structures with a short temporal delay. In
      the advanced rotation, the LEV in the rotational phase could not maintain the
      attachment. Thus, the rotational lift was not able to work. On the contrary, the
      temporal response delay benefitted the wing in the delayed rotation. Therefore,
      the wing in the delayed rotation had both a similar level of the mean CL and a
      higher marked L/D than those of the advanced rotation. Such results indicate that
      the high Re could interrupt lift augmentation mechanisms, and these augmentations
      would not be suitable for a heavier MAV. In conclusion, using adequate wing
      kinematics to acquire estimations of the weight and range of the Re is highly
      recommended at the aerodynamic design step.

PMID- 25381678
TI  - Evidence appraisal of Kim G, Kim MH, Lee SM, Choi SJ, Shin YH, Jeong HJ. Effect
      of pre-warmed intravenous fluids on perioperative hypothermia and shivering after
      ambulatory surgery under monitored anesthesia care [published online ahead of
      print April 1, 2014]. J Anesth.

PMID- 25381679
TI  - Donald Hugh Enlow, 1927-2014.

PMID- 25381680
TI  - Gerald Vale, 1926-2013.

PMID- 25381681
TI  - Self-repositioning of an embolized patent ductus arteriosus device--a nightmare
      turned into sweet dreams.
AB  - A 7-month-old boy was admitted for the device closure of symptomatic patent
      ductus arteriosus (PDA) with moderate pulmonary hypertension. The PDA measured
      4.2 mm with adequate ampulla. It was closed with an 8-6 mm Heart R device from
      pulmonary artery (PA) end. Post extubation, the device embolized to proximal
      descending thoracic aorta just distal to PDA ampulla. While attempting to snare
      from the venous side, the device self-repositioned to PDA. It was stable
      thereafter and patient was discharged after 2 days. We report a complication,
      which got self-corrected.

PMID- 25381683
TI  - Influence of shell thickness on the performance of light-emitting devices based
      on CdSe/Zn1-X CdX S core/shell heterostructured quantum dots.
AB  - CdSe/Zn1-X CdX S core/shell heterostructured quantum dots (QDs) with varying
      shell thicknesses are studied as the active material in a series of
      electroluminescent devices. "Giant" CdSe/Zn1-X CdX S QDs (e.g., CdSe core radius
      of 2 nm and Zn1-X CdX S shell thickness of 6.3 nm) demonstrate a high device
      efficiency (peak EQE = 7.4%) and a record-high brightness (>100 000 cd m(-2) ) of
      deep-red emission, along with improved device stability. 

PMID- 25381685
TI  - Global stroke bill of rights.

PMID- 25381682
TI  - Perivascular-derived stem cells with neural crest characteristics are involved in
      tendon repair.
AB  - Tendons and ligaments exhibit limited regenerative capacity following injury,
      with damaged tissue being replaced by a fibrotic scar. The physiological role of
      scar tissue is complex and has been studied extensively. In this study, we
      demonstrate that rat tendons contain a unique subpopulation of cells exhibiting
      stem cell characteristics, including clonogenicity, multipotency, and self
      renewal capacity. Additionally, these putative stem cells expressed markers
      consistent with neural crest stem cells (NCSCs). Using immunofluorescent
      labeling, we identified P75(+) (p75 neurotrophin receptor) cells in the
      perivascular regions of the native rat tendon. Importantly, P75(+) cells were
      frequently localized near vascular cells and increased in number within the
      peritenon after injury. Ultrastructural analysis showed that perivascular cells
      detached from vessels in response to injury, migrated into the interstitial
      space, and deposited extracellular matrix. Characterization of P75(+) cells
      isolated from the scar tissue indicated that this population also expressed the
      NCSC markers, Vimentin, Sox10, and Snail. In conclusion, our results suggest that
      neural crest-like stem cells of perivascular origin reside within the rat
      peritenon and give rise to scar-forming stromal cells following tendon injury. 

PMID- 25381686
TI  - Challenges in integrating international evidence relating to stroke
      rehabilitation: experiences from a Cochrane systematic review.
AB  - There are many randomized controlled trials relating to stroke rehabilitation
      being carried out in China, which are often published in Chinese-language
      journals. A recent update to our Cochrane systematic review of physical
      rehabilitation to improve function and mobility after stroke included 96 trials;
      over half (51) were conducted in China; 37 of these included studies were
      published in Chinese. Analyses within this Cochrane review support the conclusion
      that physical rehabilitation, using a mix of components from different
      approaches, is effective for the recovery of function and mobility after stroke.
      The inclusion of the Chinese studies had a substantial impact on the volume of
      evidence and, consequently, the conclusions. In this paper, we explore whether it
      is appropriate to draw implications for clinical practice throughout the world
      from evidence relating to a complex rehabilitation intervention delivered within
      one particular geographical healthcare setting. We explore the unique challenges
      associated with incorporating the body of evidence from China, particularly the
      Chinese-language publications, and identify the ongoing debate about the quality
      of Chinese research publications. We conclude that the growing body of evidence
      from China has important implications for future systematic reviews and evidence
      based stroke care, but analysis and interpretation raise challenges, and improved
      reporting is critical. 

PMID- 25381687
TI  - Recent advances in TeleStroke: a systematic review on applications in prehospital
      management and Stroke Unit treatment or TeleStroke networking in developing
      countries.
AB  - TeleStroke has become an increasing means to overcome shortage of stroke
      expertise in underserved areas. This rapidly growing field has triggered a large
      amount of publications in recent years. We aimed to analyze recent advances in
      the field of telemedicine for acute stroke, with main focus on prehospital
      management, Stroke Unit treatment and network implementations in developing
      countries. Out of 260 articles, 25 were selected for this systematic review: 9
      regarding prehospital management, 14 regarding Stroke Unit treatment and 2
      describing a network in developing countries. Prehospital management showed that
      stroke recognition can start at the dispatch emergency call, important clinical
      information can be electronically transmitted to hospitals before admission and
      even acute treatment such as thrombolysis can be initiated in the prehospital
      field if ambulances are equipped with CT scan and point-of-care laboratory.
      Articles on remote clinical examination, telemedical imaging interpretation,
      trial recruitment and cost-effectiveness described various aspects of Stroke Unit
      treatment within TeleStroke networks, underlining reliability, safety and cost
      savings of these systems of care. Only one network was described to have been
      implemented in a developing/emerging nation. TeleStroke is a growing field
      expanding its focus to a broader spectrum of stroke care. It still seems to be
      underused, particularly in developing countries. 

PMID- 25381688
TI  - Bilateral corona radiata infarcts: a new topographic location of Foix-Chavany
      Marie syndrome.

PMID- 25381689
TI  - Decompressive craniectomy for stroke after intravenous thrombolytic therapy.

PMID- 25381690
TI  - Effects of organized education by video on knowledge of early stroke symptoms
      among a Chinese rural population.

PMID- 25381691
TI  - Percheron artery occlusion: an uncommon cause of decreased arousal.

PMID- 25381692
TI  - The predictive value of aortic stiffness for asymptomatic coronary artery disease
      in a stroke/transient ischemic attack: role of hypertension and antihypertensive
      drugs.

PMID- 25381693
TI  - Response to Varol et al.'s letter.

PMID- 25381694
TI  - Axonal excitability in primary amyloidotic neuropathy.
AB  - INTRODUCTION: Acquired and hereditary amyloidosis can cause peripheral
      neuropathy, but the mechanisms by which this occurs have not been established.
      Threshold tracking techniques allow in vivo assessment of the properties of the
      axonal membrane and may shed light on pathogenetic mechanisms underlying
      neuropathic disorders. METHODS: We studied 10 subjects with primary amyloidosis
      using conventional nerve conduction studies and quantitative sensory, autonomic,
      and axonal excitability testing of median motor and sensory fibers. RESULTS: As
      expected, subjects with amyloidosis had evidence of small- and large-fiber
      neuropathy on conventional testing. There was no significant difference in axonal
      excitability between subjects and controls apart from the stimulus required to
      activate sensory fibers. CONCLUSIONS: Amyloid-related neuropathy does not produce
      a change in membrane potential as either a primary or secondary event. This
      suggests that ischemia and axonal compression are unlikely mechanisms for the
      neuropathy.

PMID- 25381695
TI  - To what extent is allergen exposure a risk factor for the development of allergic
      disease?
AB  - The role of allergen exposure in the development of allergic disease has been a
      matter of considerable debate, and our understanding of the importance of
      allergens has evolved over the last 25 years. Several observational and primary
      prevention studies have investigated these relationships, and different studies
      reported inconsistent, and sometimes opposite findings. It has to be emphasized
      that a clear understanding of how aeroallergen exposure occurs, and accurate and
      reproducible measurement of exposure are essential prerequisites for
      understanding the role of exposure. However, our current understanding of how we
      get exposed to allergens is not based on solid evidence, but on a number of
      assumptions, and we urgently need to develop better proxy measures (or indices)
      of exposure. In addition, the relative importance of the timing of exposure (e.g.
      early compared to exposure in later life) is unknown. It is also unclear which
      route of exposure is the most relevant (e.g. inhaled vs. oral vs.
      transcutaneous). Available data suggest that the dose-response relationship
      between allergen exposure and allergic disease may differ between different
      allergens, dose ranges and exposure patterns, and these relationships may further
      differ between different populations and geographical areas. It is increasingly
      clear that childhood asthma and atopy are not single phenotypes, and it is likely
      that allergen exposure has different effect on distinct subgroups under the
      umbrella terms of 'sensitization' and 'asthma'. Susceptibility to allergen
      exposure, other environmental exposures and their interactions may also differ
      between individuals with different genetic predispositions. However, the precise
      nature of these complex relationships is unclear. We need a holistic approach
      offered by systems biology, with integration of information on the standardized
      and reliable measures of exposures (including allergens and other relevant
      exposures) with genetic and biological data to fully understand the role of
      allergens in the development of allergic disease.

PMID- 25381696
TI  - Highly permselective membrane surface modification by cold plasma-induced
      grafting polymerization of molecularly imprinted polymer for recognition of
      pyrethroid insecticides in fish.
AB  - Specific molecularly imprinted membranes (MIMs) for pyrethroid insecticides were
      developed and characterized for the first time in this study by cold plasma
      induced grafting polymerization using methacrylic acid as a functional monomer
      and cypermethrin (CYP) as a template. The nonimprinted membranes (NIMs) were also
      synthesized using the same procedure without the template. Meanwhile, AFM, XPS,
      ATR-FTIR, contact angle, and permselectivity experiments were conducted to
      elucidate the imprinting and recognition properties of MIMs. Results demonstrated
      that MIMs exhibited excellent imprinting effect and high permselectivity. A
      molecularly imprinted-membrane-assisted solvent extraction (MI-MASE) method based
      on the MIMs was established. The operating conditions were optimized for group
      selective extraction of the five pyrethroid insecticides. Compared with NIMs,
      higher extraction recoveries (83.8% to 100.6%) of the five pyrethroid
      insecticides by gas chromatography-electron capture detector (GC-ECD) were
      obtained using MIMs at three spiked levels in fish samples; the RSD values were
      lower than 8.3%. The limits of detection (LOD) and quantification (LOQ) defined
      as the concentrations at which the signal-to-noise (S/N) ratio is 3:1 and 10:1,
      respectively, were in the range of 0.26 to 0.42 MUg/kg and 0.77 to 1.27 MUg/kg,
      respectively. No matrix effect of the developed MI-MASE was observed by gas
      chromatography/tandem mass spectrometry (GC/MS/MS). These results demonstrated a
      highly selective, efficient, and environment-friendly MI-MASE technique for
      preconcentration and purification of pyrethroid insecticides from seafood,
      followed by GC-ECD and GC/MS/MS. The excellent applicability and potential of MI
      MASE for routine monitoring of pyrethroid pesticides in food samples has also
      been confirmed. 

PMID- 25381697
TI  - Using virtual reality to improve the efficacy of cognitive-behavioral therapy
      (CBT) in the treatment of late-life anxiety: preliminary recommendations for
      future research.
AB  - Cognitive-behavioral therapy (CBT) using traditional exposure techniques (i.e.
      imaginal and in vivo) seems less effective to treat anxiety in older adults than
      in younger ones. This is particularly true when imaginal exposure is used to
      confront the older patient to inaccessible (e.g. fear of flying) or less
      tangible/controllable anxiety triggers (e.g. fear of illness). Indeed, imaginal
      exposure may become less effective as the person gets older since normal aging is
      characterized by the decline in cognitive functions involved in the creation of
      vivid/detailed mental images. One way to circumvent this difficulty is to expose
      the older patient to a virtual environment that does not require the ability to
      imagine the frightening situation. In virtuo exposure has proven to be efficient
      to treat anxiety in working-age people. In virtuo exposure could be employed to
      improve the efficacy of CBT with exposure sessions in the treatment of late-life
      anxiety? The current paper explores this question and suggests new research
      avenues. 

PMID- 25381698
TI  - Alloreactive regulatory T cells generated with retinoic acid prevent skin
      allograft rejection.
AB  - CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells mediate immunological self
      tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite
      of vitamin A, has been reported to enhance the differentiation of Treg cells in
      the presence of TGF-beta. In this study, we show that the co-culture of naive T
      cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from
      BALB/c mice in the presence of TGF-beta, RA, and IL-2 resulted in a striking
      enrichment of Foxp3(+) T cells. These RA in vitro-induced regulatory T (RA-iTreg)
      cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased
      homing potential, and expressed several cell surface molecules related to Treg
      cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell
      proliferation and inhibited cytokine production by T cells in in vitro assays.
      Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression
      and their suppressive capacity. Finally, RA-iTreg cells showed alloantigen
      specific immunosuppressive capacity in a skin allograft model in immunodeficient
      mice. Altogether, these data indicate that functional and stable allogeneic
      specific Treg cells may be generated using TGF-beta, RA, and IL-2. Thus, RA-iTreg
      cells may have a potential use in the development of more effective cellular
      therapies in clinical transplantation. 

PMID- 25381699
TI  - Correlation between heart rate variability indexes and aerobic physiological
      variables in patients with COPD.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have shown a relationship between the
      level of physical fitness and autonomic variables. However, these relationships
      have not been investigated in patients with chronic obstructive pulmonary disease
      (COPD). The objective of this study was to correlate the resting heart rate
      variability (HRV) indexes with aerobic physiological variables obtained at a
      maximal exercise test in patients with COPD. METHODS: Thirty-seven patients with
      COPD (63 (59-70) years; 46 (35.4-63.7) forced expiratory volume in 1 s (FEV1)%)
      underwent assessment of autonomic modulation at rest for 20 min to determine the
      HRV indexes in time and frequency domains. Soon after that, the patients
      performed an incremental exercise test to determine the anaerobic threshold
      (GET), the peak oxygen uptake (VO 2PEAK) and the velocity corresponding to VO
      2PEAK (vVO 2PEAK). RESULTS: The indexes that express parasympathetic component as
      RMSSD (11.4 [7.5-23.8], HF (ms(2)) (35 [17-195] and SD1 (8.1 [5.3-16.8]),
      correlated with GET (r = 0.39; r = 0.43; r = 0.39 respectively). The indexes that
      represent the overall variability, SDNN (19.5 [13.9-28.8]), LF (ms(2)) (111 [38
      229]), and SD2 (26.8 [18.6-35.4]) correlated with vVO 2PEAK (r = 0.37; r = 0.38;
      r = 0.37; r = 0.44; r = 0.43; r = 0.46 respectively). Likewise, the indexes LF
      (ms(2)), LF (nu) (63.2 [46-77,9]), HF (nu) (36.8 [22.1-54]), and LF/HF (1.7 [0.9
      3.5]) correlated with VO 2PEAK (r = 0.35; r = 0.35; r = -0.35; r = 0.40
      respectively). CONCLUSIONS: This study demonstrated that HRV indexes at rest may
      become a predictive tool for aerobic capacity in COPD patients after the
      development of more consistent methods.

PMID- 25381700
TI  - Fanconi anemia and solid malignancies in childhood: a national retrospective
      study.
AB  - BACKGROUND: Fanconi anemia (FA) predisposes to hematologic disorders and myeloid
      neoplasia in childhood and to solid cancers, mainly oral carcinomas, in early
      adulthood. Few cases of solid cancers have been reported in childhood.
      PROCEDURES: We conducted a national retrospective study of solid tumors occurring
      in patients registered with or determined to have FA during childhood in France.
      Phenotypic features, tumor type, cancer treatment, and outcome were analyzed.
      Whenever available, fresh-frozen tumors were analyzed by microarray-based
      comparative genomics hybridization. RESULTS: We identified eight patients with FA
      with solid tumor from 1986 to 2012. For two patients, the diagnosis of FA was
      unknown at the time of cancer diagnosis. Moreover, we identified one fetus with a
      brain tumor. All patients showed failure to thrive and had dysmorphic features
      and abnormal skin pigmentation. Seven patients had BRCA2/FANCD1 mutations; five
      of these featured more than one malignancy and the median age at the time of
      cancer diagnosis was 11 months (range 0.4-3 years). Solid tumor types included
      five nephroblastomas, two rhabdomyosarcomas, two neuroblastomas, and three brain
      tumors. Two children died from the toxic effects of chemotherapy, two patients
      from the cancer, and one patient from secondary leukemia. Only one BRCA2 patient
      was alive more than 3 years after diagnosis, after tailored chemotherapy.
      CONCLUSION: Solid tumors are rare in FA during childhood, except in patients with
      BRCA2/FANCD1 mutations. The proper genetic diagnosis is mandatory to tailor the
      treatment.

PMID- 25381701
TI  - Porphyrins as excellent dyes for dye-sensitized solar cells: recent developments
      and insights.
AB  - Dye-sensitized solar cells (DSSCs) have attracted much attention as an
      alternative to silicon-based solar cells because of their low-cost production and
      high power conversion efficiency. Among various sensitizers, numerous research
      activities have been focused on porphyrins due to their strong absorption bands
      in the visible region, versatile modifications of their core, and facile tuning
      of the electronic structures. In 2005-2007, Officer and Gratzel et al. had
      achieved a rapid increase in the power conversion efficiency of porphyrin DSSCs
      from a few percent to as much as 7%. Encouraged by these pioneering works,
      further high-performance porphyrin dyes have been developed in the last decade.
      These studies have provided us profound hints for the rational design of
      sensitizers toward highly efficient DSSCs. Push-pull structures and/or pi
      extensions have made porphyrins panchromatic in visible and even near-infrared
      regions. Consequently, porphyrin sensitizers have exhibited power conversion
      efficiencies that are comparable to or even higher than those of well-established
      highly efficient DSSCs based on ruthenium complexes. So far the power conversion
      efficiency has increased up to ca. 13% by using a push-pull porphyrin with a
      cobalt-based redox shuttle. In this perspective, we review the recent
      developments in the synthetic design of porphyrins for highly efficient DSSCs. 

PMID- 25381702
TI  - The impact of psychological empowerment and organizational commitment on Chines
      nurses' job satisfaction.
AB  - Abstract Background: Research findings have shown that job satisfaction of
      Chinese nurses is at a low level. Limited studies have focused on the impact of
      psychological empowerment and organizational commitment on job satisfaction of
      Chinese nurses. Aims: The aim of this study is to describe job satisfaction,
      psychological empowerment and organizational commitment of Chinese nurses and to
      explore the impact of psychological empowerment and organizational commitment on
      the nurses' job satisfaction. Methods: A total of 726 nurses were recruited in a
      convenience sample from 10 tertiary hospitals. Data were collected using four
      questionnaires including Job Satisfaction Survey, Psychological Empowerment
      Scale, Organizational Commitment Scale and Demographic Questionnaire. Descriptive
      analysis, correlation and stepwise multiple regression were used for data
      analysis. Results: Nurses' job satisfaction, psychological empowerment, and
      organizational commitment were identified at moderate levels. Nurses' job
      satisfaction and psychological empowerment were significantly different in terms
      of age and length of service; nurse job satisfaction varied with respect to
      marital status. Findings further indicated that nurse job satisfaction was
      positively correlated with psychological empowerment and organizational
      commitment. Psychological empowerment, organizational commitment, and marital
      status were significant predicting factors of nurse job satisfaction.
      Conclusions: This study provides evidence to help nursing managers and health
      policy-makers to develop intervention programs aimed at enhancing nurse job
      satisfaction and retaining nurses.

PMID- 25381703
TI  - George Bartzokis.

PMID- 25381704
TI  - Enoch Callaway.

PMID- 25381705
TI  - Merton Sandler.

PMID- 25381706
TI  - Daniel W. Hommer.

PMID- 25381707
TI  - Nancy Kishlar Mello.

PMID- 25381708
TI  - Joseph Clayton Schoolar.

PMID- 25381709
TI  - Ellen Stover.

PMID- 25381710
TI  - Turan M Itil.

PMID- 25381711
TI  - Harry L June.

PMID- 25381712
TI  - William L Woolverton.

PMID- 25381713
TI  - Perspectives on working and training in global health and international emergency
      medicine.

PMID- 25381714
TI  - Sub-lethal UV-C radiation induces callose, hydrogen peroxide and defence-related
      gene expression in Arabidopsis thaliana.
AB  - Exposure of plants to UV-C irradiation induces gene expression and cellular
      responses that are commonly associated with wounding and pathogen defence, and in
      some cases can lead to increased resistance against pathogen infection. We
      examined, at a physiological, molecular and biochemical level, the effects of and
      responses to, sub-lethal UV-C exposure on Arabidopsis plants when irradiated with
      increasing dosages of UV-C radiation. Following UV-C exposure plants had reduced
      leaf areas over time, with the severity of reduction increasing with dosage.
      Severe morphological changes that included leaf glazing, bronzing and curling
      were found to occur in plants treated with the 1000 J.m(-2) dosage. Extensive
      damage to the mesophyll was observed, and cell death occurred in both a dosage-
      and time-dependent manner. Analysis of H2O2 activity and the pathogen defence
      marker genes PR1 and PDF1.2 demonstrated induction of these defence-related
      responses at each UV-C dosage tested. Interestingly, in response to UV-C
      irradiation the production of callose (beta-1,3-glucan) was identified at all
      dosages examined. Together, these results show plant responses to UV-C
      irradiation at much lower doses than have previously been reported, and that
      there is potential for the use of UV-C as an inducer of plant defence.

PMID- 25381716
TI  - G-protein-coupled receptor type A heteromers as an emerging therapeutic target.
AB  - INTRODUCTION: The discovery of receptor-receptor interactions (RRIs) in the early
      1980s provided evidence that G-protein-coupled receptors (GPCRs) operate not only
      as monomers but also as heteromers, in which integration of the incoming signals
      takes place already at the plasma membrane level through allosteric RRIs. These
      integrative mechanisms give sophisticated dynamics to the structure and function
      of these receptor assemblies in terms of modulation of recognition, G-protein
      signaling and selectivity and switching to beta-arrestin signaling. AREAS
      COVERED: The present review briefly describes the concept of direct RRI and the
      available data on the mechanisms of oligomer formation. Further, pharmacological
      data concerning the best characterized heteromers involving type A GPCRs will be
      analyzed to evaluate their profile as possible targets for the treatment of
      various diseases, in particular of impacting diseases of the CNS. EXPERT OPINION:
      GPCR heteromers have the potential to open a completely new field for
      pharmacology with likely a major impact in molecular medicine. Novel
      pharmacological strategies for the treatment of several pathologies have already
      been proposed. However, several challenges still exist to accurately characterize
      the role of the identified heteroreceptor complexes in pathology and to develop
      heteromer-specific ligands capable of efficiently exploiting their
      pharmacological features.

PMID- 25381715
TI  - Evaluation of intraspecies interactions in biofilm formation by Methylobacterium
      species isolated from pink-pigmented household biofilms.
AB  - Concern regarding household biofilms has grown due to their widespread existence
      and potential to threaten human health by serving as pathogen reservoirs.
      Previous studies identified Methylobacterium as one of the dominant genera found
      in household biofilms. In the present study, we examined the mechanisms
      underlying biofilm formation by using the bacterial consortium found in household
      pink slime. A clone library analysis revealed that Methylobacterium was the
      predominant genus in household pink slime. In addition, 16 out of 21 pink
      pigmented bacterial isolates were assigned to the genus Methylobacterium.
      Although all of the Methylobacterium isolates formed low-level biofilms, the
      amount of the biofilms formed by Methylobacterium sp. P-1M and P-18S was
      significantly increased by co-culturing with other Methylobacterium strains that
      belonged to a specific phylogenetic group. The single-species biofilm was easily
      washed from the glass surface, whereas the dual-species biofilm strongly adhered
      after washing. A confocal laser scanning microscopy analysis showed that the dual
      species biofilms were significantly thicker and tighter than the single-species
      biofilms. 

PMID- 25381717
TI  - A data-rich recruitment core to support translational clinical research.
AB  - BACKGROUND: Underenrollment of clinical studies wastes resources and delays
      assessment of research discoveries. We describe the organization and impact of a
      centralized recruitment core delivering comprehensive recruitment support to
      investigators. METHODS: The Rockefeller University Center for Clinical and
      Translational Science supports a centralized recruitment core, call center,
      Research Volunteer Repository, data infrastructure, and staff who provide expert
      recruitment services to investigators. During protocol development, consultations
      aim to optimize enrollment feasibility, develop recruitment strategy, budget, and
      advertising. Services during study conduct include advertising placement,
      repository queries, call management, prescreening, referral, and visit
      scheduling. Utilization and recruitment outcomes are tracked using dedicated
      software. RESULTS: For protocols receiving recruitment services during 2009-2013:
      median time from initiation of recruitment to the first enrolled participant was
      10 days; of 4,047 first-time callers to the call center, 92% (n = 3,722) enrolled
      in the Research Volunteer Repository, with 99% retention; 23% of Repository
      enrollees subsequently enrolled in >=1 research studies, with 89% retention. Of
      volunteers referred by repository queries, 49% (280/537) enrolled into the study,
      with 92% retained. CONCLUSIONS: Provision of robust recruitment infrastructure
      including expertise, a volunteer repository, data capture and real-time analysis
      accelerates protocol accrual. Application of recruitment science improves the
      quality of clinical investigation.

PMID- 25381718
TI  - Reduction of Powerplex((r)) Y23 reaction volume for genotyping buccal cell
      samples on FTA(TM) cards.
AB  - PowerPlex((r)) Y23 is a novel kit for Y-STR typing that includes new highly
      discriminating loci. The Israel DNA Database laboratory has recently adopted it
      for routine Y-STR analysis. This study examined PCR amplification from 1.2-mm FTA
      punch in reduced volumes of 5 and 10 MUL. Direct amplification and washing of the
      FTA punches were examined in different PCR cycle numbers. One short robotically
      performed wash was found to improve the quality and the percent of profiles
      obtained. The optimal PCR cycle number was determined for 5 and 10 MUL reaction
      volumes. The percent of obtained profiles, color balance, and reproducibility
      were examined. High-quality profiles were achieved in 90% and 88% of the samples
      amplified in 5 and 10 MUL, respectively, in the first attempt. Volume reduction
      to 5 MUL has a vast economic impact especially for DNA database laboratories.

PMID- 25381719
TI  - Ginsenoside F1 attenuates hyperpigmentation in B16F10 melanoma cells by inducing
      dendrite retraction and activating Rho signalling.
AB  - Ginsenoside F1 (GF1) is a metabolite produced by hydrolysis of the ginsenoside Re
      and Rg1 in Panax ginseng. According to various studies, high amounts of ginseng
      components are absorbed in the metabolized form, which are key constituents
      responsible for the biological effects of P. ginseng. Recently, GF1 was reported
      to have beneficial effects on skin. However, there has not been a sound
      understanding of its antimelanogenic effect and underlying molecular mechanisms.
      In this study, GF1 reduced alpha-melanocyte-stimulating hormone-induced melanin
      secretion in B16F10 cell culture media by 60%. However, it did not suppress
      intracellular melanin levels, tyrosinase activity and expression.
      Immunofluorescence assay showed that GF1 had no effect on melanosome transport,
      but significantly induced dendrite retraction. Pull-down assay demonstrated that
      GF1 primarily modulates the Rho family GTPases resulting in dendrite retraction.
      Collectively, these data suggest that GF1 could act as a potent skin-whitening
      agent. 

PMID- 25381720
TI  - Methods of biological fluids sample preparation - biogenic amines,
      methylxanthines, water-soluble vitamins.
AB  - In recent years demands on the amount of information that can be obtained from
      the analysis of a single sample have increased. For time and economic reasons it
      is necessary to examine at the same time larger number of compounds, and
      compounds from different groups. This can best be seen in such areas as clinical
      analysis. In many diseases, the best results for patients are obtained when
      treatment fits the individual characteristics of the patient. Dosage monitoring
      is important at the beginning of therapy and in the full process of treatment. In
      the treatment of many diseases biogenic amines (dopamine, serotonin) and
      methylxanthines (theophylline, theobromine, caffeine) play an important role.
      They are used as drugs separately or in combination with others to support and
      strengthen the action of other drugs - for example, the combination of caffeine
      and paracetamol. Vitamin supplementation may be also an integral part of the
      treatment process. Specification of complete sample preparation parameters for
      extraction of the above compounds from biological matrices has been reviewed.
      Particular attention was given to the preparation stage and extraction methods.
      This review provides universal guidance on establishing a common procedures
      across laboratories to facilitate the preparation and analysis of all discussed
      compounds.

PMID- 25381722
TI  - Graphitic carbon nitride nanoribbons: graphene-assisted formation and synergic
      function for highly efficient hydrogen evolution.
AB  - The development of new promising metal-free catalysts is of great significance
      for the electrocatalytic hydrogen evolution reaction (HER). Herein, a rationally
      assembled three-dimensional (3D) architecture of 1D graphitic carbon nitride (g
      C3N4) nanoribbons with 2D graphene sheets has been developed by a one-step
      hydrothermal method. Because of the multipathway of charge and mass transport,
      the hierarchically structured g-C3N4 nanoribbon-graphene hybrids lead to a high
      electrocatalytic ability for HER with a Tafel slope of 54 mV decade(-1), a low
      onset overpotential of 80 mV and overpotential of 207 mV to approach a current of
      10 mA cm(-2), superior to those non-metal materials and well-developed metallic
      catalysts reported previously. This work presents a great advance for designing
      and developing highly efficient metal-free catalyst for hydrogen evolution.

PMID- 25381721
TI  - Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B
      treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular
      carcinoma (HCC) and ultimately liver-related death. Although oral antiviral
      therapy for patients with CHB reduces the risk of such complications, once
      cirrhosis is established, the benefits of antiviral therapy are not robustly
      demonstrated. According to traditional Chinese medicine (TCM), some Chinese
      herbal medicines promote blood circulation and soften hard masses, and therefore
      they may block and reverse hepatic fibrosis. The aim of this study is to evaluate
      the effects of TCM tablets of the compound biejia ruangan (RGT) administered for
      fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or
      hepatitis B virus (HBV)-related compensated cirrhosis. METHODS/DESIGN: This
      multicenter, centrally randomized, double-blind, placebo-controlled, parallel
      group study is planned to complete within 5 years. For the study, 1,000 with CHB
      or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a
      treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control
      group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary
      end points are the development of HCC and liver-related death. Secondary end
      points include disease progression and overall survival. DISCUSSION: Although
      antiviral therapy can achieve sustained suppression of HBV replication, thereby
      preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs)
      retain a higher risk for HCC compared with patients with inactive disease.
      Although previous clinical trials with RGT have confirmed the efficacy of
      blocking and reversing hepatic fibrosis in patients with CHB or compensated
      cirrhosis, the long-term risk for HCC or disease progression in these patients
      treated with combination of RGT and NUCs compared with NUCs alone is unclear.
      Therefore, it is necessary to investigate the effects of the RGT blockade and
      reversal of hepatic fibrosis on the development of HCC in patients with CHB or
      HBV-related compensated cirrhosis in large, prospective, multicenter, double
      blind, randomized, controlled trials in China. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.

PMID- 25381723
TI  - Factor V Leiden mutation increases the risk for venous thromboembolism in cancer
      patients - results from the Vienna Cancer And Thrombosis Study (CATS).
AB  - BACKGROUND: Patients with cancer are at an increased risk for venous
      thromboembolism (VTE). The risk varies markedly in different patient populations.
      Factor V (FV) Leiden is the most common genetic risk factor for VTE, and the
      impact of FV Leiden on cancer-associated thrombosis is not yet fully elucidated.
      OBJECTIVE: To study the impact of FV Leiden on the risk of thrombosis in cancer
      patients. METHODS: In the prospective observational Vienna Cancer And Thrombosis
      Study (CATS), 982 patients were included and were followed until occurrence of
      VTE or death, for a maximum period of 2 years. FV Leiden was determined by
      genotyping at inclusion. Main outcome measures were symptomatic or lethal
      objectively confirmed VTE. RESULTS: Of the 982 patients, FV Leiden was diagnosed
      in 72 (7.3%, 70 were heterozygous and 2 were homozygous). Ten of 72 (13.9%)
      patients with FV Leiden developed VTE, whereas this was the case in 69 of 910
      (7.6%) patients without FV Leiden. In multivariate analysis that included age,
      sex, different tumor types, tumor stage, newly diagnosed vs. recurrence of
      disease, and the treatment modalities, the hazard ratio was 2.0 (95% confidence
      interval 1.0-4.0). In Kaplan-Meier analysis, the probability for development of
      VTE was 13% in those with and 5.7% in those without FV Leiden after 6 months;
      after 1 year, the corresponding risks were 15% and 7.3%. CONCLUSIONS: FV Leiden
      is a genetically determined and thus disease-independent parameter, which is
      associated with VTE in cancer patients and could therefore be used for individual
      risk assignment.

PMID- 25381724
TI  - Histology of microscopic colitis-review with a practical approach for
      pathologists.
AB  - Microscopic colitis has emerged as a major cause of chronic watery non-bloody
      diarrhoea, particularly in elderly females. The term is used as an umbrella term
      to categorize a subgroup of colitides with distinct clinicopathological
      phenotypes and no significant endoscopic abnormalities. Lymphocytic colitis is
      defined by an increased number of surface intraepithelial lymphocytes, and
      collagenous colitis by a thickened collagen band underneath the surface
      epithelium. There is increased inflammation in the lamina propria, but only
      little or no crypt architectural distortion. Incomplete and variant forms showing
      less characteristic features have been reported under different names. The
      differential diagnosis mainly includes resolving infectious colitis and changes
      related to the intake of drugs such as non-steroidal anti-inflammatory drugs.
      Substantial clinical and histological overlap between lymphocytic and collagenous
      colitis has been described, raising the suspicion that the conditions are two
      histological manifestations of the same entity, possibly representing different
      manifestations during the disease course or different stages of disease
      development. In this review, we provide a practical approach for pathologists,
      with a focus on diagnostic criteria and differential diagnosis, and discuss
      recent insights into the pathogenesis of disease and the relationship with
      classic chronic inflammatory bowel disease, i.e. Crohn's disease and ulcerative
      colitis. 

PMID- 25381725
TI  - Prevalence of spondyloarthritis symptom in inflammatory bowel disease patients: A
      questionnaire survey.
AB  - OBJECTIVES: We clarified the prevalence of spondyloarthritis (SpA) symptom in
      inflammatory bowel disease (IBD). METHODS: We performed the questionnaire survey
      of SpA symptom in IBD patients on their office visit. RESULTS: One hundred and
      thirty seven patients were evaluated. The SpA features group included 46 (33.6%)
      patients (32 Men). Among them there were 22 Crohn's disease (CD) patients and 24
      ulcerative colitis (UC) patients. The patients had a mean age of 48.3 years with
      a mean disease duration of 12.3 years. Non-SpA group (66.4%) included 91 patients
      (49 Men). Among them there were 27 CD patients and 64 UC patients. The patients
      had a mean age of 43.3 years with a mean disease duration of 9.2 years. In
      univariate analysis, the SpA group (33.6%) had longer disease duration than non
      SpA group (p < 0.05). However, age at onset and sex were not significantly
      different among the groups. Multivariate analysis showed that disease duration
      was independently associated with SpA symptom (OR, 1.05; 95% CI, 1-1.09; p =
      0.036). CONCLUSIONS: The prevalence of SpA symptom was relatively higher than
      what we had expected. Physicians should consider SpA when they observe IBD
      patients with arthralgia, and refer them to an appropriate department if needed.

PMID- 25381726
TI  - Pediatric Rheumatology Association of Japan recommendation for vaccination in
      pediatric rheumatic diseases.
AB  - Pediatric Rheumatology Association of Japan has developed evidence-based
      guideline of vaccination in pediatric rheumatic diseases (PRDs) as a part of
      Guideline of Vaccination for Pediatric Immunocompromised Hosts. Available
      articles on vaccination in both adult rheumatic diseases and PRDs were analyzed.
      Non-live vaccines are generally safe and effective in patients with PRDs on
      corticosteroid, immunosuppressant, and/or biologics, although efficacy may be
      attenuated under high dose of the drugs. On the other hand, efficacy and safety
      of live-attenuated vaccine for the patients on such medication have not been
      established. Thus, live-attenuated vaccines should be withheld and, if indicated,
      may be considered as a clinical trial under the approval by Institutional Review
      Board. All patients with PRDs anticipating treatment with immunosuppressants or
      biologics should be screened for infection of hepatitis B and C and tuberculosis
      before the commencement of medication. Varicella vaccine should be considered in
      sensitive patients ideally 3 weeks or longer before the commencement of
      immunosuppressants, corticosteroids, or biologics. Bacille Calmette-Guerin should
      be withheld at least for 6 months after birth, if their mothers have received
      anti-tumor necrosis factor-alpha antibodies during the second or third trimester
      of pregnancy. 

PMID- 25381727
TI  - A long-term follow-up of Japanese mother and her daughter with Blau syndrome:
      Effective treatment of anti-TNF inhibitors and useful diagnostic tool of joint
      ultrasound examination.
AB  - Blau syndrome (BS) is an autosomal dominant autoinflammatory disease associated
      with NOD2 gene mutations. It is characterized by arthritis, skin rash, and
      uveitis. Here, we report contrasting outcomes of a daughter and her mother with
      BS. Their long-term follow-up revealed the efficacy of anti-tumor necrosis factor
      inhibitor (TNF) with respect to BS. Joint findings of BS feature tenosynovitis
      over articular synovitis on ultrasonography. BS might be one of the differential
      diagnoses of juvenile idiopathic arthritis and rheumatoid arthritis.

PMID- 25381728
TI  - Subperiosteal inflammatory pseudotumor mimicking primary malignant bone tumor: A
      case report.
AB  - We report a case of IgG4-positive inflammatory pseudotumor mimicking malignant
      bone tumor. Biopsy revealed no tumor cells. Surgical excision was performed and
      an abscess developing beneath the periosteum was observed with Streptococcus
      constellatus. Preoperative serum IgG4 value of 120 mg/dl normalized
      postoperatively to 80.6 mg/dl. It was difficult to distinguish inflammatory
      pseudotumor from sarcoma because it developed under the periosteum. In such
      cases, it is important to measure blood IgG4 values and perform tissue staining
      and culturing.

PMID- 25381729
TI  - Delayed wound healing after forefoot surgery in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To elucidate the systemic and local risk factors and the effect of
      surgical procedures for delayed wound healing after forefoot surgery in patients
      with rheumatoid arthritis (RA). METHODS: Fifty forefoot surgeries were performed
      in 39 patients using resection arthroplasty or a joint-preserving procedure (25
      feet for each procedure). The associations between the occurrence of delayed
      wound healing and clinical variables, radiological assessment, or surgical
      procedures were analyzed. RESULTS: Delayed wound healing was recorded in nine
      feet of eight patients. The duration of RA was significantly longer in the
      delayed healing group than that in the healed group. Age, sex, smoking history,
      concomitant diabetes, and RA medication did not differ between the groups.
      Radiological evaluation showed significant differences between groups in
      metatarsophalangeal dorsal flexion angle. The shortened length of the fourth and
      the fifth metatarsal bones affected the occurrence of the complication. The joint
      preserving procedure had significantly less delayed wound healing compared with
      resection arthroplasty. CONCLUSIONS: Preoperative dorsoplantar deformity and
      perioperative tissue damage can cause delayed wound healing after forefoot
      surgery in RA patients.

PMID- 25381730
TI  - Sonographic measurements of low-echoic synovial area in the dorsal aspect of
      metatarsophalangeal joints in healthy subjects.
AB  - INTRODUCTION: Assessment of synovitis in the metatarsophalangeal (MTP) joints
      with ultrasound has been shown to improve the accuracy of assessment of
      rheumatoid arthritis (RA). However, the presence of intraarticular low-echoic
      synovial area (LESA) in the MTP joints in healthy subjects complicates the
      sonographic assessment of these joints. METHOD: Healthy subjects with no
      arthritic symptoms in their MTP joints were recruited. All subjects completed a
      questionnaire and underwent physical examination and sonographic assessment.
      LESAs in the dorsal aspect of all MTP joints were measured in the longitudinal
      view. RESULTS: One thousand non-arthritic MTP joints in 100 healthy subjects
      (female 73, mean age 41.0 years old) were evaluated. Measurable LESAs were
      identified in all joints assessed. Mean length of LESA in each of the 1st-5th MTP
      joints was 17.8, 13.9, 11.9, 10.6, and 9.2 mm, respectively, whereas mean
      thickness was 2.4, 2.4, 1.8, 1.2, and 0.8 mm, respectively. Multivariate linear
      regression models identified the difference between 1st and 5th MTP joints as the
      most independently influential factor on the measurement of LESA. CONCLUSIONS:
      Our data provide the normal reference values for the measurements of LESA in
      Japanese, which should be taken into consideration when the synovitis in MTP
      joints is evaluated with ultrasound.

PMID- 25381731
TI  - Hepatitis B vaccination is effective by subcutaneous route in children with
      bleeding disorders: a universal data collection database analysis.
AB  - Subcutaneous (SQ) vs. intramuscular (IM) vaccination may cause fewer injection
      site complications in children with bleeding disorders, but little is known about
      comparative immunogenicity. To compare immunogenicity of hepatitis B virus (HBV)
      vaccination administered SQ or IM to individuals <2 years old with bleeding
      disorders, we performed a retrospective analysis of HBV surface antibody titres
      among patients enrolled in the universal data collection database who had
      received three doses of HBV vaccine solely by one route (SQ or IM). Data reviewed
      were from an initial visit before 24 months of age, until time of hepatitis
      antibody titre testing. The SQ and IM study groups did not differ in
      demographics, haemophilia type or severity or bleeding history. The mean age at
      the time of HBV surface antibody (anti-HBs) testing was 56.9 +/- 20.3 months.
      Eighty-five of 92 subjects (92.4%) who received vaccine SQ developed a positive
      antibody titre (>12 IU/L), compared to 101/114 (88.6%) who received IM (P =
      0.30). There was no statistically significant difference in distribution of titre
      values. The average age of the subjects at time of testing was 53 +/- 20 months
      in the SQ group vs. 60 +/- 20 months in the IM group (P = 0.02). The average time
      between the last dose of vaccine and anti-HBs testing was 47.6 +/- 18.5 months
      among SQ vaccinated subjects vs. 51.6 +/- 20.5 months in the IM group (P = 0.2).
      Immunogenicity to hepatitis B vaccination by the SQ and IM routes is similar.

PMID- 25381732
TI  - Two-year death and loss to follow-up outcomes by source of referral to HIV care
      for HIV-infected patients initiating antiretroviral therapy in rural Mozambique.
AB  - We studied patient outcomes by type of referral site following 2 years of
      combination antiretroviral therapy (cART) during scale-up from June 2006 to July
      2011 in Mozambique's rural Zambezia Province. Loss to follow-up (LTFU) was
      defined as no contact within 60 days after scheduled medication pickup. Endpoints
      included LTFU, mortality, and combined mortality/LTFU; we used Kaplan-Meier and
      cumulative incidence estimates. The referral site was the source of HIV testing.
      We modeled 2-year outcomes using Cox regression stratified by district, adjusting
      for sociodemographics and health status. Of 7,615 HIV-infected patients >=15
      years starting cART, 61% were female and the median age was 30 years. Two-year
      LTFU was 38.1% (95% CI: 36.9-39.3%) and mortality was 14.2% (95% CI 13.2-15.2%).
      Patients arrived from voluntary counseling and testing (VCT) sites (51%), general
      outpatient clinics (21%), antenatal care (8%), inpatient care (3%),
      HIV/tuberculosis/laboratory facilities (<4%), or other sources of referral (14%).
      Compared with VCT, patients referred from inpatient, tuberculosis, or antenatal
      care had higher hazards of LTFU. Adjusted hazard ratios (AHR; 95% CI) for 2-year
      mortality by referral site (VCT as referent) were inpatient 1.87 (1.36-2.58),
      outpatient 1.44 (1.11-1.85), and antenatal care 0.69 (0.43-1.11) and for
      mortality/LTFU were inpatient 1.60 (1.34-1.91), outpatient 1.17 (1.02-1.33),
      tuberculosis care 1.38 (1.08-1.75), and antenatal care 1.24 (1.06-1.44). That
      source of referral was associated with mortality/LTFU after adjusting for patient
      characteristics at cART initiation suggests that (1) additional unmeasured
      factors are influential, and (2) retention programs may benefit from targeting
      patient populations based on source of referral with focused counseling and/or
      social support.

PMID- 25381734
TI  - Waveguide coupled resonance fluorescence from on-chip quantum emitter.
AB  - Resonantly driven quantum emitters offer a very promising route to obtain highly
      coherent sources of single photons required for applications in quantum
      information processing (QIP). Realizing this for on-chip scalable devices would
      be important for scientific advances and practical applications in the field of
      integrated quantum optics. Here we report on-chip quantum dot (QD) resonance
      fluorescence (RF) efficiently coupled into a single-mode waveguide, a key
      component of a photonic integrated circuit, with a negligible resonant laser
      background and show that the QD coherence is enhanced by more than a factor of 4
      compared to off-resonant excitation. Single-photon behavior is confirmed under
      resonant excitation, and fast fluctuating charge dynamics are revealed in
      autocorrelation g((2)) measurements. The potential for triggered operation is
      verified in pulsed RF. These results pave the way to a novel class of integrated
      quantum-optical devices for on-chip quantum information processing with embedded
      resonantly driven quantum emitters. 

PMID- 25381733
TI  - Determination of the electrostatic potential distribution in
      Pt/Fe:SrTiO3/Nb:SrTiO3 thin-film structures by electron holography.
AB  - We determined the electrostatic potential distribution in pristine
      Pt/Fe:SrTiO3/Nb:SrTiO3 structures by electron holography experiments, revealing
      the existence of a depletion layer extending into the Nb-doped bottom electrode.
      Simulations of potential profiles in metal-insulator-metal structures were
      conducted assuming different types and distributions of dopants. It is found that
      the presence of acceptor-type dopant concentrations at the Fe:SrTiO3/Nb:SrTiO3
      interface with a donor-doped insulating layer provides a good match to the
      measured profile. Such acceptor-type interface concentrations may be associated
      with Sr vacancies on the Nb:SrTiO3 side of the bottom interface. 

PMID- 25381735
TI  - Using strategic foresight to assess conservation opportunity.
AB  - The nature of conservation challenges can foster a reactive, rather than
      proactive approach to decision making. Failure to anticipate problems before they
      escalate results in the need for more costly and time-consuming solutions.
      Proactive conservation requires forward-looking approaches to decision making
      that consider possible futures without being overly constrained by the past.
      Strategic foresight provides a structured process for considering the most
      desirable future and for mapping the most efficient and effective approaches to
      promoting that future with tools that facilitate creative thinking. The process
      involves 6 steps: setting the scope, collecting inputs, analyzing signals,
      interpreting the information, determining how to act, and implementing the
      outcomes. Strategic foresight is ideal for seeking, recognizing, and realizing
      conservation opportunities because it explicitly encourages a broad-minded,
      forward-looking perspective on an issue. Despite its potential value, the
      foresight process is rarely used to address conservation issues, and previous
      attempts have generally failed to influence policy. We present the strategic
      foresight process as it can be used for proactive conservation planning,
      describing some of the key tools in the foresight tool kit and how they can be
      used to identify and exploit different types of conservation opportunities.
      Scanning is an important tool for collecting and organizing diverse streams of
      information and can be used to recognize new opportunities and those that could
      be created. Scenario planning explores how current trends, drivers of change, and
      key uncertainties might influence the future and can be used to identify barriers
      to opportunities. Backcasting is used to map out a path to a goal and can
      determine how to remove barriers to opportunities. We highlight how the foresight
      process was used to identify conservation opportunities during the development of
      a strategic plan to address climate change in New York State. The plan identified
      solutions that should be effective across a range of possible futures.
      Illustrating the application of strategic foresight to identify conservation
      opportunities should provide the impetus for decision makers to explore strategic
      foresight as a way to support more proactive conservation policy, planning, and
      management. 

PMID- 25381737
TI  - Effect of incorporating aromatic and chiral groups on the dielectric properties
      of poly(dimethyltin esters).
AB  - High-dielectric constant materials are critical for numerous applications such as
      photovoltaics, photonics, transistors, and capacitors. There are numerous
      polymers used as dielectric layers in these applications but can suffer from
      having a low dielectric constant, small band gap, or ferroelectricity. Here, the
      structure-property relationship of various poly(dimethyltin esters) is described
      that look to enhance the dipolar and atomic polarization component of the
      dielectric constant. These polymers are also modeled using first principles
      calculations based on density functional theory (DFT) to predict such values as
      the total, electronic, and ionic dielectric constant as well as structure. A
      strong correlation is achieved between the theoretical and experimental values
      with the polymers exhibiting dielectric constants >4.5 with dissipation on the
      order of 10(-3) -10(-2) .

PMID- 25381738
TI  - Molecular Characterization of a Thermophilic and Salt- and Alkaline-Tolerant
      Xylanase from Planococcus sp. SL4, a Strain Isolated from the Sediment of a Soda
      Lake.
AB  - To enrich the genetic resource of microbial xylanases with high activity and
      stability under alkaline conditions, a xylanase gene (xynSL4) was cloned from
      Planococcus sp. SL4, an alkaline xylanase-producing strain isolated from the
      sediment of soda lake Dabusu. Deduced XynSL4 consists of a putative signal
      peptide of 29 residues and a catalytic domain (30-380 residues) of glycosyl
      hydrolase family 10, and shares the highest identity of 77% with a hypothetical
      protein from Planomicrobium glaciei CHR43. Phylogenetic analysis indicated that
      deduced XynSL4 is closely related with thermophilic and alkaline xylanases from
      Geobacillus and Bacillus species. The gene xynSL4 was expressed heterologously in
      Escherichia coli and the recombinant enzyme showed some superior properties.
      Purified recombinant XynSL4 (rXynSL4) was highly active and stable over the
      neutral and alkaline pH range from 6 to 11, with maximum activity at pH 7 and
      more than 60% activity at pH 11. It had an apparent temperature optimum of 70
      degrees C and retained stable at this temperature in the presence of substrate.
      rXynSL4 was highly halotolerant, retaining more than 55% activity with 0.25-3.0 M
      NaCl and was stable at the concentration of NaCl up to 4M. The enzyme activity
      was significantly enhanced by beta-mercaptoethanol and Ca(2+) but strongly
      inhibited by heavy-metal ions and SDS. This thermophilic and alkaline- and salt
      tolerant enzyme has great potential for basic research and industrial
      applications.

PMID- 25381736
TI  - Longitudinal volumetric brain changes in autism spectrum disorder ages 6-35
      years.
AB  - Since the impairments associated with autism spectrum disorder (ASD) tend to
      persist or worsen from childhood into adulthood, it is of critical importance to
      examine how the brain develops over this growth epoch. We report initial findings
      on whole and regional longitudinal brain development in 100 male participants
      with ASD (226 high-quality magnetic resonance imaging [MRI] scans; mean inter
      scan interval 2.7 years) compared to 56 typically developing controls (TDCs) (117
      high-quality scans; mean inter-scan interval 2.6 years) from childhood into
      adulthood, for a total of 156 participants scanned over an 8-year period. This
      initial analysis includes between one and three high-quality scans per
      participant that have been processed and segmented to date, with 21% having one
      scan, 27% with two scans, and 52% with three scans in the ASD sample;
      corresponding percentages for the TDC sample are 30%, 30%, and 40%. The
      proportion of participants with multiple scans (79% of ASDs and 68% of TDCs) was
      high in comparison to that of large longitudinal neuroimaging studies of typical
      development. We provide volumetric growth curves for the entire brain, total gray
      matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical
      white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and
      total ventricles. Mean volume of cortical WM was reduced significantly. Mean
      ventricular volume was increased in the ASD sample relative to the TDCs across
      the broad age range studied. Decreases in regional mean volumes in the ASD sample
      most often were due to decreases during late adolescence and adulthood. The
      growth curve of whole brain volume over time showed increased volumes in young
      children with autism, and subsequently decreased during adolescence to meet the
      TDC curve between 10 and 15 years of age. The volume of many structures continued
      to decline atypically into adulthood in the ASD sample. The data suggest that ASD
      is a dynamic disorder with complex changes in whole and regional brain volumes
      that change over time from childhood into adulthood.

PMID- 25381739
TI  - Expression of the mexA Gene Requires the DNA Helicase RecG in Pseudomonas
      aeruginosa PAO1.
AB  - This study provides evidence that RecG regulates the expression of the OxyR
      independent gene mexA in Pseudomonas aeruginosa PAO1. A reduction in mexA
      expression was observed in the absence of RecG, but not OxyR, by northern blot
      and quantitative real-time PCR analyses. The canonical palindromic RecG binding
      sequence was present upstream of the mexA promoter, and bound purified RecG and
      single strand-binding protein. These data reveal a novel mechanism of OxyR
      independent gene transcription by RecG.

PMID- 25381740
TI  - Optimization of yeast surface-displayed cDNA library screening for low abundance
      targets.
AB  - The yeast surface-displayed cDNA library has been used to identify unknown
      antigens. However, when unknown target antigens show moderate-to-low abundance,
      some modifications are needed in the screening process. In this study, a
      directional random-primed cDNA library was used to increase the number of
      candidates for the unknown antigen. To avoid the loss of target yeast clones that
      express proteins at a low frequency in the cDNA library, a comprehensive
      monitoring system based on magnetic-activated cell sorting, fluorescence
      activated cell sorting, and immunofluorescence was established, and a small
      number of target yeast cells was successfully enriched. These results showed that
      our optimized method has potential application for identifying rare unknown
      antigens of the human monoclonal antibody. 

PMID- 25381741
TI  - Antibacterial Mode of Action of Cinnamomum verum Bark Essential Oil, Alone and in
      Combination with Piperacillin, Against a Multi-Drug-Resistant Escherichia coli
      Strain.
AB  - This study aimed to investigate the mechanism of action of the cinnamon bark
      essential oil (CB), when used singly and also in combination with piperacillin,
      for its antimicrobial and synergistic activity against beta-lactamase TEM-1
      plasmid-conferred Escherichia coli J53 R1. Viable count of this combination
      showed a complete killing profile at 20 h and further confirmed its synergistic
      effect by reducing the bacteria cell numbers. Analysis on the stability of
      treated cultures for cell membrane permeability by CB when tested against sodium
      dodecyl sulfate revealed that the bacterial cell membrane was disrupted by the
      essential oils. Scanning electron microscopy observation and bacterial surface
      charge measurement also revealed that CB causes irreversible membrane damage and
      reduces the bacterial surface charge. In addition, bioluminescence expression of
      Escherichia coli [pSB1075] and E. coli [pSB401] by CB showed reduction,
      indicating the possibility of the presence of quorum sensing (QS) inhibitors. Gas
      chromatography and mass spectrometry of the essential oil of Cinnamomum verum
      showed that trans-cinnamaldehyde (72.81%), benzyl alcohol (12.5%), and eugenol
      (6.57%) were the major components in the essential oil. From this study, CB has
      the potential to reverse E. coli J53 R1 resistance to piperacillin through two
      pathways; modification in the permeability of the outer membrane or bacterial QS
      inhibition. 

PMID- 25381742
TI  - Morphological, molecular, and biochemical characterization of astaxanthin
      producing green microalga Haematococcus sp. KORDI03 (Haematococcaceae,
      Chlorophyta) isolated from Korea.
AB  - A unicellular red microalga was isolated from environmental freshwater in Korea,
      and its morphological, molecular, and biochemical properties were characterized.
      Morphological analysis revealed that the isolate was a unicellular biflagellated
      green microalga that formed a non-motile, thick-walled palmelloid or red
      aplanospore. To determine the taxonomical position of the isolate, its 18S rRNA
      and rbcL genes were sequenced and phylogenetic analysis was performed. We found
      that the isolate was clustered together with other related Haematococcus strains
      showing differences in the rbcL gene. Therefore, the isolated microalga was
      classified into the genus Haematococcus, and finally designated Haematococcus sp.
      KORDI03. The microalga could be cultivated in various culture media under a broad
      range of pH and temperature conditions. Compositions of the microalgal cellular
      components were analyzed, and its protein, carbohydrate, and lipid compositions
      were estimated to be 21.1 +/- 0.2%, 48.8 +/- 1.8%, and 22.2 +/- 0.9%,
      respectively. In addition, D-glucose and D-mannose were the dominant
      monosaccharides in the isolate, and its amino acids were composed mainly of
      aspartic acid, glutamic acid, alanine, and leucine. Moreover, several
      polyunsaturated fatty acids accounted for about 80% of the total fatty acids in
      Haematococcus sp. KORDI03, and the astaxanthin content in the red aplanospores
      was estimated to be 1.8% of the dry cell weight. To the best of our knowledge,
      this is the first report of an Haematococcus sp. isolated from Korea, which may
      be used for bioresource production in the microalgal industry.

PMID- 25381743
TI  - Comparative effectiveness and safety of various treatment procedures for lower
      pole renal calculi: a systematic review and network meta-analysis.
AB  - OBJECTIVE: To compare the effectiveness of various treatments used for lower pole
      renal calculi. METHODS: We searched PubMed, EMBASE, CINAHL, the Cochrane
      Collaboration's Database of Systematic Reviews, the Cochrane Collaboration
      Central Register of Controlled Clinical Trials as well as ClinicalTrials.gov for
      reports up to 1 April 2014. The search was supplemented with abstract reports
      from various urology conferences. All randomised, 'blinded' clinical studies
      including patients treated for lower pole renal calculi of <20 mm were included
      for review. Two authors independently reviewed 5 194 articles, and identified and
      selected 13 trials for analysis. Network meta-analysis was performed to generate
      comparative statistics, while quality was assessed with the Jadad composite scale
      and risk of bias. RESULTS: All treatment methods examined: percutaneous
      nephrolithotomy (PNL), ureterorenoscopy (URS) and extracorporeal shockwave
      lithotripsy (SWL) with an adjuvant therapy (such as inversion, hydration and
      forced diuresis) were more effective than SWL therapy alone, with risk ratios
      (95% confidence intervals) of being stone free of: PNL 2.19 (1.62-2.96); URS 1.23
      (1.03-1.48); and SWL with an adjuvant therapy 1.30 (1.03-1.63). However, patients
      treated with the other treatment methods also had a higher risk of adverse events
      (AEs) compared with SWL, but there was no evidence of a convincing difference
      between the various techniques and AEs. CONCLUSION: In stones of <10 mm, SWL with
      an adjuvant therapy appears to have better stone clearance, lower risk of AEs,
      and need for further treatment. PNL was most effective treating larger stones,
      after considering both effectiveness and safety of treatment. These should be
      considered by both physicians and patients alike when considering the choice of
      treatment and in the revision of clinical practice guidelines.

PMID- 25381745
TI  - Towards chiral distributions of dopants in microporous frameworks: helicoidal
      supramolecular arrangement of (1R,2S)-ephedrine and transfer of chirality.
AB  - A molecular-mechanics computational study is performed in order to analyze the
      arrangement of (1R,2S)-(-)-ephedrine molecules within the 12-MR channels of the
      AFI aluminophosphate microporous framework and the influence on the spatial
      distribution of dopants embedded in the tetrahedral network. Results showed that
      ephedrine molecules arrange exclusively as dimers by pi-pi stacking of the
      aromatic rings within the AFI channels. Interestingly, the asymmetric nature of
      ephedrine and the presence of H-bond-forming groups (NH2 and OH) involve a
      preferential orientation where consecutive dimers within the channels are rotated
      by an angle of +30 degrees ; this is driven by the establishment of inter-dimer H
      bonds. This preferential orientation leads to the development of a supramolecular
      enantiomerically-pure helicoidal (chiral) arrangement of ephedrine dimers. In
      addition, the computational results demonstrate that the particular molecular
      structure of ephedrine imparts a strong trend to attract negative charges to the
      vicinity of the NH2(+) positively-charged groups. Hence divalent dopants such as
      Mg, whose replacement by trivalent Al in the aluminophosphate network involves
      the generation of a negative charge, will tend to locate close to the NH2(+)
      molecular groups, suggesting that an imprinting of the organic arrangement to the
      spatial distribution of dopants would be feasible. Combined with the trend of
      ephedrine to arrange in a helicoidal fashion, an enantiomerically-pure helicoidal
      distribution of dopants would be expected, thus inducing a new type of chirality
      in microporous materials. 

PMID- 25381746
TI  - A painful stiff neck following an ear, nose, and throat surgical procedure: case
      report.
AB  - Grisel syndrome is a rare, nontraumatic atlantoaxial subluxation, typical of
      developmental ages and characterized by head flexion/rotation and painful
      fixation. Neurological symptoms may occur. It is secondary to head/neck
      infections and ear, nose, and throat surgery (adenoidectomy, tonsillectomy, and
      mastoidectomy). Here, we report the case of a child who presented a painful stiff
      neck following an adenotonsillectomy, with imaging evidencing an atlantoaxial
      subluxation. The child showed improvement in his condition following a
      conservative treatment with antibiotics, anti-inflammatory, and analgesic therapy
      and cervical collar. We believe it is of great significance for clinicians taking
      into account this peculiar condition in the differential diagnosis of a stiff
      neck in pediatric patients, thus avoiding misdiagnosis and delays. Indeed, its
      diagnosis is mainly based on a focused anamnesis associated with the detection of
      the typical neuroradiological findings. 

PMID- 25381744
TI  - Helicobacter cinaedi induced typhlocolitis in Rag-2-deficient mice.
AB  - BACKGROUND: Helicobacter cinaedi, an enterohepatic helicobacter species (EHS), is
      an important human pathogen and is associated with a wide range of diseases,
      especially in immunocompromised patients. It has been convincingly demonstrated
      that innate immune response to certain pathogenic enteric bacteria is sufficient
      to initiate colitis and colon carcinogenesis in recombinase-activating gene (Rag)
      2-deficient mice model. To better understand the mechanisms of human IBD and its
      association with development of colon cancer, we investigated whether H. cinaedi
      could induce pathological changes noted with murine enterohepatic helicobacter
      infections in the Rag2(-/-) mouse model. MATERIALS AND METHODS: Sixty 129SvEv
      Rag2(-/-) mice mouse were experimentally or sham infected orally with H. cinaedi
      strain CCUG 18818. Gastrointestinal pathology and immune responses in infected
      and control mice were analyzed at 3, 6 and 9 months postinfection (MPI). H.
      cinaedi colonized the cecum, colon, and stomach in infected mice. RESULTS: H.
      cinaedi induced typhlocolitis in Rag2(-/-) mice by 3 MPI and intestinal lesions
      became more severe by 9 MPI. H. cinaedi was also associated with the elevation of
      proinflammatory cytokines, interferon-gamma, tumor-necrosis factor-alpha, IL
      1beta, IL-10; iNOS mRNA levels were also upregulated in the cecum of infected
      mice. However, changes in IL-4, IL-6, Cox-2, and c-myc mRNA expressions were not
      detected. CONCLUSIONS: Our results indicated that the Rag2(-/-) mouse model will
      be useful to continue investigating the pathogenicity of H. cinaedi, and to study
      the association of host immune responses in IBD caused by EHS.

PMID- 25381747
TI  - Photoinduced charge transfer in a conformational switching chlorin dimer
      azafulleroid in polar and nonpolar media.
AB  - In the present study, a biomimetic reaction center model, that is, a molecular
      triad consisting of a chlorin dimer and an azafulleroid, is synthesized and its
      photophysical properties are studied in comparison with the corresponding
      molecular dyad, which consists only of a chlorin monomer and an azafulleroid. As
      evidenced by (1) H NMR, UV/Vis, and fluorescence spectroscopy, the chlorin dimer
      azafulleroid folds in nonpolar media into a C2 -symmetric geometry through
      hydrogen bonding, resulting in appreciable electronic interactions between the
      chlorins, whereas in polar media the two chlorins diverge from contact.
      Femtosecond transient absorption spectroscopy studies reveal longer charge
      separated states for the chlorin dimer-azafulleroid; ~1.6 ns in toluene, compared
      with the lifetime of ~0.9 ns for the corresponding chlorin monomer-azafulleroid
      in toluene. In polar media, for example, benzonitrile, similar charge-separated
      states are observed, but the lifetimes are inevitably shorter: 65 and 73 ps for
      the dimeric and monomeric chlorin-azafulleroids, respectively. Nanosecond
      transient absorption and singlet oxygen phosphorescence studies corroborate that
      in toluene, the charge-separated state decays indirectly via the triplet excited
      state to the ground state, whereas in benzonitrile, direct recombination to the
      ground state is observed. Complementary DFT studies suggest two energy-minima
      conformations, that is, a folded chlorin dimer-azafulleroid, which is present in
      nonpolar media, and another conformation in polar media, in which the two
      hydrophobic chlorins wrap the azafulleroid. Inspection of the frontier molecular
      orbitals shows that in the folded conformation, the HOMO on each chlorin is
      equivalent and is shared owing to partial pi-pi overlap, resulting in
      delocalization of the conjugated pi electrons, whereas the wrapped conformation
      lacks this stabilization. As such, the longer charge-separated lifetime for the
      dimer is rationalized by both the electron donor-acceptor separation distance and
      the stabilization of the radical cation through delocalization. The chlorin
      folding seems to change the photophysical properties in a manner similar to that
      observed in the chlorophyll dimer in natural photosynthetic reaction centers. 

PMID- 25381748
TI  - Can a back pain screening tool help classify patients with acute pain into risk
      levels for chronic pain?
AB  - BACKGROUND: The 9-item STarT-Back screening tool was developed in primary care
      patients with low back pain (LBP) to identify those at greatest risk for chronic
      pain and requiring targeted treatment. We conducted a secondary data analysis
      study to examine the performance of comparable questionnaire items in a sample of
      primary care patients with well-defined acute LBP. METHODS: In a prospective
      cohort study, 605 primary care patients with LBP of less than 30 days answered a
      questionnaire with 6 items identical and 3 items analogous to the 9-item STarT
      Back. Participants were followed up at 6 months and 2 years. STarT-Back rules
      were applied to classify participant's risk of chronic LBP, and the performance
      of the screening items in predicting outcomes was assessed using likelihood
      ratios. RESULTS: The proportion of patients with chronic pain at follow-up was
      considerably lower (6 months: 22%; 2 years: 25%) than in the STarT-Back
      validation cohort (40%) of patients with pain of any duration. The probability of
      developing chronic pain given a high-risk designation by items similar to the
      STarT-Back increased the pre-test probability to 31% and 35%. Likelihood ratios
      were close to 1. CONCLUSIONS: A risk classification schema using the recommended
      cut-off scores with items similar to the STarT-Back in a primary care population
      with strictly defined acute LBP had limited ability to identify persons who
      progressed to chronic pain. The results suggest caution when applying the STarT
      Back in patients with acute LBP and a need to consider a modification of its cut
      offs.

PMID- 25381750
TI  - Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization
      Studies in gene-targeted replacement mice.
AB  - SCOPE: Of the three human apolipoprotein E (APOE) alleles, the epsilon3 allele is
      most common, which may be a result of adaptive evolution. In this study, we
      investigated whether the APOE genotype affects body weight and energy metabolism
      through regulation of fatty acid utilization. METHODS AND RESULTS: Targeted
      replacement mice expressing the human APOE3 were significantly heavier on low-
      and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food
      intake and dietary energy yields as well as fat mass were increased in APOE3
      mice. Fatty acid mobilization determined as activation of adipose tissue lipase
      and fasting plasma nonesterified fatty acid levels were significantly lower in
      APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of
      proteins involved in fatty acid oxidation in skeletal muscle. CONCLUSION: Our
      data suggest that APOE3 is associated with the potential to more efficiently
      harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers
      tend to increase fatty acid mobilization and utilization as fuel substrates
      especially under high-fat intake. The different handling of dietary energy may
      have contributed to the evolution and worldwide distribution of the epsilon3
      allele.

PMID- 25381749
TI  - Differential effects of clozapine, metoclopramide, haloperidol and risperidone on
      acquisition and performance of operant responding in rats.
AB  - RATIONALE: Prior research has not systematically investigated the effects of
      systemic antipsychotic drugs on operant response acquisition, specifically their
      behavioural microstructure, reinforcement blunting and relative potency in
      acquisition compared to performance once operant responding has stabilized.
      OBJECTIVES: This study aims to systematically investigate the effects of
      systemically administered clozapine, metoclopramide, haloperidol and risperidone
      during free operant response acquisition and performance. METHODS: Following
      magazine training, food-restricted male Wistar rats lever pressed for food reward
      in 15 min daily operant conditioning sessions. RESULTS: All drugs suppressed
      operant response acquisition and performance. Risperidone and metoclopramide, but
      not clozapine or haloperidol, suppressed operant responding more potently during
      acquisition than performance. The dopamine D2-like receptor antagonists
      haloperidol and metoclopramide that affect the ventral and dorsal striatum
      blunted reinforcement and decreased inactive lever presses in acquisition. In
      contrast, the atypical antipsychotics clozapine and risperidone that affect the
      ventral striatum and prefrontal cortex failed to decrease inactive lever presses
      during acquisition, suggesting a possible decision-making deficit. Haloperidol
      decreased active lever pressing over performance days. The drugs did not appear
      to affect rats' sensitivity to active lever press outcome, even though they
      suppressed active lever pressing. CONCLUSIONS: Results suggest that reinforcement
      impact during operant acquisition is dependent on dopamine D2 receptors while
      drugs affecting, among other areas, the prefrontal cortex produce a deficit in
      ability to suppress inactive lever press responses.

PMID- 25381751
TI  - A review of gliptins for 2014.
AB  - INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) occupy an
      increasing place in the armamentarium of drugs used for the management of
      hyperglycaemia and offer new opportunities for a personalized medicine in
      patients with Type 2 diabetes. AREAS COVERED: An updated review providing an
      analysis of available recent data with commercialized DPP-4 inhibitors, with a
      special focus on: differences between the various molecules, novelties regarding
      their mechanism of action, clinical efficacy in mono- and various combined
      therapies, comparison with other new therapies, efficacy-safety profile in at
      risk patients, concern about pancreatic safety, perspectives in cardiovascular
      prevention and, finally, a selection of remaining unanswered important questions
      for the clinician. EXPERT OPINION: DPP-4 inhibitors offer various advantages when
      compared to other glucose-lowering agents. Despite they have been commercialized
      since a few years only, available data obtained in randomised controlled trials
      are of better quality compared to those available with ancient classical glucose
      lowering agents, especially in more fragile populations such as elderly people,
      individuals with renal impairment or at high cardiovascular risk and patients at
      higher risk of hypoglycaemia. However, there remain uncertainties and
      controversies that should be resolved by further ongoing large prospective
      controlled trials and increasing clinical experience combined with a careful post
      marketing surveillance.

PMID- 25381752
TI  - Refractive index sensing with Fano resonant plasmonic nanostructures: a symmetry
      based nonlinear approach.
AB  - Sensing using surface plasmon resonances is one of the most promising practical
      applications of plasmonic nanostructures and Fano resonances allow achieving a
      lower detection limit thanks to their narrow spectral features. However, a narrow
      spectral width of the subradiant mode in a plasmonic system, as observed in the
      weak coupling regime, is in general associated with a low modulation of the
      complete spectral response. In this article, we show that this limitation can be
      overcome by a nonlinear approach based on second harmonic generation and its
      dependence on symmetry at the nanoscale. The Fano resonant systems considered in
      this work are gold nanodolmens. Their linear and nonlinear responses are
      evaluated using a surface integral equation method. The numerical results
      demonstrate that a variation of the refractive index of the surrounding medium
      modifies the coupling between the dark and bright modes, resulting in a
      modification of the electromagnetic wave scattered at the second harmonic
      wavelength, especially the symmetry of the nonlinear emission. Reciprocally, we
      show that evaluating the asymmetry of the nonlinear emission provides a direct
      measurement of the gold nanodolmens dielectric environment. Interestingly, the
      influence of the refractive index of the surrounding medium on the nonlinear
      asymmetry parameter is approximately 10 times stronger than on the spectral
      position of the surface plasmon resonance: hence, smaller refractive index
      changes can be detected with this new approach. Practical details for an
      experimental realization of this sensing scheme are discussed and the resolution
      is estimated to be as low as Deltan = 1.5 * 10(-3), respectively 1.5 * 10(-5),
      for an acquisition time of 60 s for an isolated gold nanodolmen, respectively an
      array of 10 * 10 nanodolmens. 

PMID- 25381753
TI  - Diagnostic accuracy of behavioral variant frontotemporal dementia consortium
      criteria (FTDC) in a clinicopathological cohort.
AB  - AIMS: The aims of this study were to assess the sensitivity of the International
      Behavioural Variant FTD Criteria Consortium (FTDC) revised criteria of
      behavioural variant frontotemporal dementia (bvFTD) in a pathological cohort and
      to determine their predictive values in a clinical context suggestive of bvFTD.
      In addition, the study aimed to assess the influence of the age at onset and
      underlying pathology in the clinicopathological correlations. METHODS:
      Retrospective, blinded review of the clinical and neuropathological data from the
      Neurological Tissue Bank of the Biobank Hospital Clinic-IDIBAPS, Barcelona
      (Spain) was conducted, assessing the fulfilment of the diagnostic criteria on a
      case-by-case basis. Two separate nonexclusive cohorts were selected: Cohort 1 (n
      = 58) subjects with pathological diagnosis of frontotemporal lobar degeneration
      (FTLD) and Cohort 2 (n = 66) subjects with the premortem diagnosis of bvFTD.
      RESULTS: The FTDC criteria reached a sensitivity of 93% for possible and 80% for
      probable bvFTD. Early-onset cases displayed significantly more disinhibition,
      loss of empathy and compulsive behaviour with respect to late-onset bvFTD,
      leading to a slightly higher sensitivity of the diagnostic criteria (97% vs.
      91%). There were no differences in the diagnostic performance between tau
      positive and tau-negative cases. In subjects clinically diagnosed as bvFTD, a
      'possible bvFTD' diagnosis reached a positive predictive value for FTLD pathology
      of 90%, irrespective of underlying proteinopathy. False-positive clinical
      diagnoses were mainly Alzheimer's disease. These cases were significantly older,
      had less family history of dementia and had a predominantly apathetic clinical
      picture. CONCLUSIONS: The revised bvFTD criteria present good sensitivity and
      positive predictive value in both early- and late-onset cases and regardless of
      the underlying FTLD pathology.

PMID- 25381755
TI  - FIB-etching of polymer/metal laminates and its effect on mechanical performance.
AB  - This paper investigates the adhesive interface in a polymer/metal (polyethylene
      terephthalate/steel) laminate that is subjected to uniaxial strain. Cross
      sections perpendicular to such interfaces were created with a focused ion beam
      and imaged with scanning electron microscopy during straining in the electron
      microscope. During in situ straining, glide steps formed by the steel caused
      traction at the interface and initiated crazes in the polyethylene terephthalate
      (PET). These crazes readily propagated along the free surface of the PET layer.
      Similar crazing has not been previously encountered in laminates that were pre
      strained or in numerical calculations. The impact of focused ion beam treatments
      on mechanical properties of the polymer/metal laminate system was therefore
      investigated. It was found that mechanical properties such as toughness of PET
      are dramatically influenced by focused ion beam etching. It was also found that
      this change in mechanical properties has a different effect on the pre-strained
      and in situ strained samples. 

PMID- 25381754
TI  - Three-dimensional quantitative structure-activity relationship analysis for human
      pregnane X receptor for the prediction of CYP3A4 induction in human hepatocytes:
      structure-based comparative molecular field analysis.
AB  - The pregnane X receptor [PXR (NR1I2)] induces the expression of xenobiotic
      metabolic genes and transporter genes. In this study, we aimed to establish a
      computational method for quantifying the enzyme-inducing potencies of different
      compounds via their ability to activate PXR, for the application in drug
      discovery and development. To achieve this purpose, we developed a three
      dimensional quantitative structure-activity relationship (3D-QSAR) model using
      comparative molecular field analysis (CoMFA) for predicting enzyme-inducing
      potencies, based on computer-ligand docking to multiple PXR protein structures
      sampled from the trajectory of a molecular dynamics simulation. Molecular
      mechanics-generalized born/surface area scores representing the ligand-protein
      binding free energies were calculated for each ligand. As a result, the predicted
      enzyme-inducing potencies for compounds generated by the CoMFA model were in good
      agreement with the experimental values. Finally, we concluded that this 3D-QSAR
      model has the potential to predict the enzyme-inducing potencies of novel
      compounds with high precision and therefore has valuable applications in the
      early stages of the drug discovery process.

PMID- 25381756
TI  - Occupational skin diseases in hairdressing apprentices - has anything changed?
AB  - BACKGROUND: Hairdressers are at risk for occupational skin diseases. Since 2008,
      an educational programme has been conducted in Danish hairdressing schools to
      prevent occupational skin diseases. Its effect is unknown. OBJECTIVE: To examine
      the current frequency of self-reported hand eczema and contact urticaria in
      Danish hairdressing apprentices as compared with controls, and to determine the
      occurrence of hand eczema and contact urticaria in hairdressing apprentices with
      different durations of exposure to the trade. METHODS: This was a cross
      sectional, web-based questionnaire study conducted among 504 hairdressing
      apprentices and a control group of 1400 adolescents from the general population.
      RESULTS: Hand eczema was significantly more prevalent in the hairdressing
      apprentices than in controls (34.5% versus 18.8%, p < 0.001). The incidence rate
      of hand eczema among hairdressing apprentices was 98 cases/1000 person-years.
      Contact urticaria was also more prevalent in the hairdressing apprentices (7.3%
      versus 4.2%, p = 0.006). Both diseases increased with increasing duration of
      exposure to the trade. CONCLUSION: Despite educational efforts to prevent
      occupational skin diseases in the hairdressing schools, Danish apprentices are
      still at increased risk for hand eczema and contact urticaria. Both diseases
      develop after only a few years of work in hairdressing. Further preventive
      strategies are warranted.

PMID- 25381758
TI  - Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege
      Reinforcement by Fas/FasL Regulating Machinery.
AB  - As a main contributing factor to low back pain, intervertebral disc degeneration
      (IDD) is the fundamental basis for various debilitating spinal diseases. The pros
      and cons of current treatment modalities necessitate biological treatment
      strategies targeting for reversing or altering the degeneration process in terms
      of molecules or genes. The advances in stem cell research facilitate the studies
      aiming for possible clinical application of stem cell therapies for IDD. Human NP
      cells are versatile with cell morphology full of variety, capable of synthesizing
      extracellular matrix components, engulfing substances by autophagy and
      phagocytosis, mitochondrial vacuolization indicating dysfunction, expressing Fas
      and FasL as significant omens of immune privileged sites. Human discs belong to
      immune privilege organs with functional FasL expression, which can interact with
      invasive immune cells by Fas-FasL regulatory machinery. IDD is characterized by
      decreased expression level of FasL with dysfunctional FasL, which in turn
      unbalances the interaction between NP cells and immune cells. Certain modulation
      factors might play a role in the process, such as miR-155. Accumulating evidence
      indicates that Fas-FasL network expresses in a variety of stem cells. Given the
      expression of functional FasL and insensitive Fas in stem cells (we term as FasL
      privilege), transplantation of stem cells into the disc may regenerate the
      degenerative disc by not only differentiating into NP-like cells, increasing
      extracellular matrix, but also reinforce immune privilege via interaction with
      immune cells by Fas-FasL network. 

PMID- 25381757
TI  - What is depression? Psychiatrists' and GPs' experiences of diagnosis and the
      diagnostic process.
AB  - The diagnosis of depression is defined by psychiatrists, and guidelines for
      treatment of patients with depression are created in psychiatry. However, most
      patients with depression are treated exclusively in general practice.
      Psychiatrists point out that general practitioners' (GPs') treatment of
      depression is insufficient and a collaborative care (CC) model between general
      practice and psychiatry has been proposed to overcome this. However, for
      successful implementation, a CC model demands shared agreement about the concept
      of depression and the diagnostic process in the two sectors. We aimed to explore
      how depression is understood by GPs and clinical psychiatrists. We carried out
      qualitative in-depth interviews with 11 psychiatrists and 12 GPs. Analysis was
      made by Interpretative Phenomenological Analysis. We found that the two groups of
      physicians differed considerably in their views on the usefulness of the concept
      of depression and in their language and narrative styles when telling stories
      about depressed patients. The differences were captured in three polarities which
      expressed the range of experiences in the two groups. Psychiatrists considered
      the diagnosis of depression as a pragmatic and agreed construct and they did not
      question its validity. GPs thought depression was a "gray area" and questioned
      the clinical utility in general practice. Nevertheless, GPs felt a demand from
      psychiatry to make their diagnosis based on instruments created in psychiatry,
      whereas psychiatrists based their diagnosis on clinical impression but used
      instruments to assess severity. GPs were wholly skeptical about instruments which
      they felt could be misleading. The different understandings could possibly lead
      to a clash of interests in any proposed CC model. The findings provide fertile
      ground for organizational research into the actual implementation of cooperation
      between sectors to explore how differences are dealt with. 

PMID- 25381759
TI  - Acute bilateral ECT in a depressed patient with a hip-aztreonam-spacer and
      subsequent maintenance ECT after prosthesis collocation.
AB  - ABSTRACT Electroconvulsive Therapy (ECT) has been demonstrated to be a safe and
      effective treatment for geriatric depression, although its application might be
      challenging when medical comorbidities exist. The present case reports a 78-year
      old man diagnosed with recurrent unipolar major depressive disorder (MDD), who
      presented with a severe depressive episode with psychotic features (DSM IV). He
      successfully received a course of bitemporal (BT) ECT with a hip-aztreonam-spacer
      due to a hip fracture that occurred during hospitalization. This was followed by
      maintenance ECT (M-ECT) with a recent prosthesis collocation. This particular
      case illustrates the importance of a multidisciplinary approach in geriatric
      patients with somatic complications receiving ECT.

PMID- 25381760
TI  - Perspectives on physiology and medicine from Nobel Prize Winners: the 64th Lindau
      Nobel Laureate Meeting.

PMID- 25381764
TI  - John Steinert Strauss (1926-2014).

PMID- 25381765
TI  - Skin Care in Organ Transplant Patients Europe meeting report from Annual Meeting,
      Leiden, The Netherlands, 15-18 May 2014.

PMID- 25381766
TI  - Psoriasis and the MAITing game: a role for IL-17A+ invariant TCR CD8+ T cells in
      psoriasis?
AB  - Recent findings have indicated that the majority of IL-17A+ CD8+ T cells in the
      blood belong to a subset of innate T cells named mucosa-associated invariant T
      cells (MAITs). In this issue, Teunissen and colleagues (2014) demonstrate that,
      although MAIT cells are found in psoriatic skin, they are not increased in
      abundance and that the majority of IL-17A+CD8+ T cells in plaques of psoriasis
      are devoid of MAIT cell characteristics.

PMID- 25381767
TI  - Manipulated microenvironment in human papilloma virus-infected epithelial cells:
      is the CD40-CD154 pathway beneficial for host or virus?
AB  - In this issue, Tummers et al. (2014) demonstrate that high-risk human papilloma
      viruses (hrHPVs) attenuate the magnitude of responses to CD40 ligation and the
      epithelial cells' (ECs) capacity to attract leukocytes. These results suggest
      that hrHPVs can escape from host immune surveillance by modulating pro
      inflammatory responses in infected ECs, resulting in persistent infections and
      potential carcinogenesis. 

PMID- 25381768
TI  - Stressing the steroids in skin: paradox or fine-tuning?
AB  - The skin has recently been found to be an extra-adrenal site for glucocorticoid
      (GC) synthesis that likely acts to modulate local inflammation. Psychological,
      physiological, and physical stress, both acute and chronic, triggers immune
      protective or -damaging responses, including increases in systemic GC levels,
      which, according to Lin et al. (this issue), may be beneficial in inflammatory
      skin disease. However, little is known about the interplay between local and
      systemic production of GCs and the effect of stress (local or systemic) in
      regulating tissue-specific GC synthesis, its impact on skin homeostasis, and its
      effect of skin disease. 

PMID- 25381771
TI  - JID VisualDx quiz: December 2014.

PMID- 25381772
TI  - Transgenic mouse technology in skin biology: generation of knockin mice.

PMID- 25381773
TI  - Cells to surgery quiz: December 2014.

PMID- 25381774
TI  - The effectiveness of telemedicine for paediatric retrieval consultations:
      rationale and study design for a pragmatic multicentre randomised controlled
      trial.
AB  - BACKGROUND: In many health systems, specialist services for critically ill
      children are typically regionalised or centralised. Studies have shown that high
      risk paediatric patients have improved survival when managed in specialist
      centres and that volume of cases is a predictor of care quality. In acute cases
      where distance and time impede access to specialist care, clinical advice may be
      provided remotely by telephone. Emergency retrieval services, attended by medical
      and nursing staff may be used to transport patients to specialist centres. Even
      with the best quality retrieval services, stabilisation of the patient and
      transport logistics may delay evacuation to definitive care. Several studies have
      examined the use of telemedicine for providing specialist consultations for
      critically ill children. However, no studies have yet formally examined the
      clinical effectiveness and economic implications of using telemedicine in the
      context of paediatric patient retrieval. METHODS/DESIGN: The study is a
      pragmatic, multicentre randomised controlled trial running over 24 months which
      will compare the use of telemedicine with the use of the telephone for paediatric
      retrieval consultations between four referring hospitals and a tertiary
      paediatric intensive care unit. We aim to recruit 160 children for whom a
      specialist retrieval consultation is required. The primary outcome measure is
      stabilisation time (time spent on site at the referring hospital by the retrieval
      team) adjusted for initial risk. Secondary outcome measures are change in
      patient's physiological status (repeated measure, two time points) scored using
      the Children's Emergency Warning Tool; change in diagnosis (repeated measure
      taken at three time points); change in destination of retrieved patients at the
      tertiary hospital (general ward or paediatric intensive care unit); retrieval
      decision, and length of stay in the Paediatric Intensive Care Unit for retrieved
      patients. The trial has been approved by the Human Research Ethics Committees of
      Children's Health Services Queensland and The University of Queensland,
      Australia. DISCUSSION: Health services are adopting telemedicine, however formal
      evidence to support its use in paediatric acute care is limited. Generalisable
      evidence is required to inform clinical use and health system policy relating to
      the effectiveness and economic implications of the use in telemedicine in
      paediatric retrieval. TRIAL REGISTRATION: Australian and New Zealand Clinical
      Trials Registry ACTRN12612000156886 .

PMID- 25381775
TI  - Assessing telomere length using surface enhanced Raman scattering.
AB  - Telomere length can provide valuable insight into telomeres and telomerase
      related diseases, including cancer. Here, we present a brand-new optical telomere
      length measurement protocol using surface enhanced Raman scattering (SERS). In
      this protocol, two single strand DNA are used as SERS probes. They are labeled
      with two different Raman molecules and can specifically hybridize with telomeres
      and centromere, respectively. First, genome DNA is extracted from cells. Then the
      telomere and centromere SERS probes are added into the genome DNA. After
      hybridization with genome DNA, excess SERS probes are removed by magnetic
      capturing nanoparticles. Finally, the genome DNA with SERS probes attached is
      dropped onto a SERS substrate and subjected to SERS measurement. Longer telomeres
      result in more attached telomere probes, thus a stronger SERS signal.
      Consequently, SERS signal can be used as an indicator of telomere length.
      Centromere is used as the inner control. By calibrating the SERS intensity of
      telomere probe with that of the centromere probe, SERS based telomere measurement
      is realized. This protocol does not require polymerase chain reaction (PCR) or
      electrophoresis procedures, which greatly simplifies the detection process. We
      anticipate that this easy-operation and cost-effective protocol is a fine
      alternative for the assessment of telomere length. 

PMID- 25381777
TI  - [Review of meta-analysis research on exercise in South Korea].
AB  - PURPOSE: The purpose of this study was to evaluate the quality of meta-analysis
      regarding exercise using Assessment of Multiple Systematic Reviews (AMSTAR) as
      well as to compare effect size according to outcomes. METHODS: Electronic
      databases including the Korean Studies Information Service System (KISS), the
      National Assembly Library and the DBpia, HAKJISA and RISS4U for the dates 1990 to
      January 2014 were searched for 'meta-analysis' and 'exercise' in the fields of
      medical, nursing, physical therapy and physical exercise in Korea. AMSTAR was
      scored for quality assessment of the 33 articles included in the study. Data were
      analyzed using descriptive statistics, t-test, ANOVA and chi2-test. RESULTS: The
      mean score for AMSTAR evaluations was 4.18 (SD=1.78) and about 67% were
      classified at the low-quality level and 30% at the moderate-quality level. The
      scores of quality were statistically different by field of research, number of
      participants, number of databases, financial support and approval by IRB. The
      effect size that presented in individual studies were different by type of
      exercise in the applied intervention. CONCLUSION: This critical appraisal of meta
      analysis published in various field that focused on exercise indicates that a
      guideline such as the PRISMA checklist should be strongly recommended for optimum
      reporting of meta-analysis across research fields.

PMID- 25381776
TI  - The uncompetitive N-methyl-D-aspartate antagonist memantine reduces binge-like
      eating, food-seeking behavior, and compulsive eating: role of the nucleus
      accumbens shell.
AB  - Binge-eating disorder is characterized by excessive, uncontrollable consumption
      of palatable food within brief periods of time. The role of the glutamatergic N
      methyl-D-aspartate (NMDA) receptor system in hedonic feeding is poorly
      understood. The aim of this study was to characterize the effects of the
      uncompetitive NMDA receptor antagonist memantine on palatable food-induced
      behavioral adaptations using a rat model, which mimics the characteristic
      symptomatology observed in binge-eating disorder. For this purpose, we allowed
      male Wistar rats to respond to obtain a highly palatable, sugary diet (Palatable
      group) or a regular chow diet (Chow control group), for 1 h a day, under a fixed
      ratio 1 (FR1) schedule of reinforcement. Upon stabilization of food responding,
      we tested the effects of memantine on the Chow and Palatable food groups' intake.
      Then, we tested the effects of memantine on food-seeking behavior, under a second
      order schedule of reinforcement. Furthermore, we investigated the effects of
      memantine on the intake of food when it was offered in an aversive, bright
      compartment of a light/dark conflict test. Finally, we evaluated the effects of
      memantine on FR1 responding for food, when microinfused into the nucleus
      accumbens (NAcc) shell or core. Memantine dose-dependently decreased binge-like
      eating and fully blocked food-seeking behavior and compulsive eating, selectively
      in the Palatable food group. The drug treatment did not affect performance of the
      control Chow food group. Finally, intra-NAcc shell, but not core, microinfusion
      of memantine decreased binge-like eating. Together, these findings substantiate a
      role of memantine as a potential pharmacological treatment for binge-eating
      disorder.

PMID- 25381778
TI  - [Effects of dignity interventions on psychosocial and existential distress in
      terminally ill patients: a meta-analysis].
AB  - PURPOSE: This study was done to evaluate the effects of dignity interventions on
      depression, anxiety and meaning of life in terminally ill patients. METHODS:
      PubMed, Cochrane Library CENTRAL, EMBASE, CINAHL and several Korean databases
      were searched. The main search strategy combined terms indicating dignity
      intervention, presence of terminal illness and study design. Methodological
      quality was assessed using Cochrane's Risk of Bias for randomized studies and
      Risk of Bias Assessment tool for non randomized studies. Data were analyzed by
      the RevMan 5.2.11 program of Cochrane Library. RESULTS: Twelve clinical trials
      met the inclusion criteria with a total of 878 participants. Dignity intervention
      was conducted for a mean of 2.2 weeks, 2.8 sessions and an average of 48.7
      minutes per session. Effect sizes were heterogeneous and subgroup analysis was
      done. Dignity interventions had a significant effect on depression (ES=-1.05,
      p<.001, I2=15%) and anxiety (ES=-1.01, p<.001, I2=0). For meaning of life,
      dignity interventions were effective (ES=-1.64, p=.005) and effect sizes were
      still heterogeneous. CONCLUSION: Results support findings that dignity
      interventions can assist terminal ill patients in reducing emotional distress and
      improving meaning of life. Further well-designed dignity studies will lead to
      better understanding of the effects of treatments on spiritual well-being.

PMID- 25381779
TI  - [Trends in nursing research in Korea: research trends for studies published from
      the inaugural issue to 2010 in the Journal of Korean Academy of Nursing and the
      journals published by member societies under Korean Academy of Nursing Science].
AB  - PURPOSE: The purpose of this study was to identify trends for studies published
      in the Journal of Korean Academy of Nursing and journals published by member
      societies from inaugural issues to 2010. METHODS: A total of 6890 studies were
      analyzed using descriptive statistics. RESULTS: Quantitative studies accounted
      for 83.6% while qualitative studies accounted for 14.4%. Most frequently used
      research designs were quasi-experimental (91.1%) for experimental research and
      survey (85.2%) for non-experimental research. Most frequent study participants
      were healthy people (35.8%), most frequent nursing interventions, nursing skills
      (53.5%), and 39.8% used knowledge, attitude and behavior outcomes for dependent
      variables. Most frequently used keyword was elderly. Survey studies decreased
      from 1991 to 2010 by approximately 50%, while qualitative studies increased by
      about 20%. True experimental research (1.2%) showed no significant changes.
      Studies focusing on healthy populations increased from 2001-2005 (37.5%) to 2006
      2010 (41.0%). From 1970 to 2010, studies using questionnaire accounted for over
      50% whereas physiological measurement, approximately 5% only. Experimental
      studies using nursing skill interventions increased from 1970-1980 (30.4%) to
      2006-2010 (64.0%). No significant changes were noted in studies using knowledge,
      attitude and behavior (39.9%) as dependent variables. CONCLUSION: The results
      suggest that further expansion of true experimental, qualitative studies and
      physiological measurements are needed.

PMID- 25381780
TI  - [Factors affecting social competence in school-aged children according to alcohol
      consumption by parents'].
AB  - PURPOSE: The purpose of this study was to identify factors affecting the social
      competence of school-aged children according alcohol consumption by their
      parents. METHODS: The participants were 558 5th grade elementary school students.
      Data were collected using structured questionnaires from September 17 to October
      2 2013, and analyzed using descriptive statistics, chi2-test, t-test, ANOVA,
      Pearson correlation coefficients, and Stepwise multiple regression analysis with
      the SPSS PC+ 21.0 program. RESULTS: Participants were classified into three
      groups according to alcohol use; Non-use parent group (52.7%), social use parent
      group (31.0%), and problem use parent group (16.3%). Participants whose parents
      were problem users had significantly lower scores on emotional awareness and
      expression (F=14.45, p<.001), social support (F=5.82, p=.003), and social
      competence (F=16.33, p<.001) compared to students in the other two groups. In
      school-aged children with parents who were alcohol abusers, the variables that
      predicted social competence was friend support (66.0%). CONCLUSION: These results
      emphasize the importance of focusing on the crucial role of peer support in the
      development of social competence in school-aged children of parents who abuse
      alcohol. Further, for these children, interventions aimed at improving social
      support and children's emotional awareness and expression may be most beneficial.

PMID- 25381781
TI  - [Bone mineral density, biochemical bone turnover markers and factors associated
      with bone health in young Korean women].
AB  - PURPOSE: This study was done to assess the bone mineral density (BMD),
      biochemical bone turnover markers (BTMs), and factors associated with bone health
      in young Korean women. METHODS: Participants were 1,298 women, ages 18-29,
      recruited in Korea. Measurements were BMD by calcaneus quantitative ultrasound,
      BTMs for Calcium, Phosphorus, Osteocalcin, and C-telopeptide cross-links (CTX),
      body composition by physical measurements, nutrients by food frequency
      questionnaire and psychosocial factors associated with bone health by self
      report. RESULTS: The mean BMD (Z-score) was -0.94. 8.7% women had lower BMD (Z
      score<=-2) and 14.3% women had higher BMD (Z-score>=0) than women of same age.
      BTMs were not significantly different between high-BMD (Z-score>=0) and low-BMD
      (Z-score<0) women. However, Osteocalcin and CTX were higher in women preferring
      caffeine intake, sedentary lifestyle and alcoholic drinks. Body composition and
      Calcium intake were significantly higher in high-BMD. Low-BMD women reported
      significantly higher susceptibility and barriers to exercise in health beliefs,
      lower bone health self-efficacy and promoting behaviors. CONCLUSION: Results of
      this study indicate that bone health of young Korean women is not good.
      Development of diverse strategies to intervene in factors such as exercise,
      nutrients, self-efficacy, health beliefs and behaviors, shown to be important,
      are needed to improve bone health.

PMID- 25381782
TI  - [Posttraumatic growth, dyadic adjustment, and quality of life in breast cancer
      survivors and their husbands].
AB  - PURPOSE: The purpose of this study was to identify whether the couple perceived
      breast cancer as a traumatic event, to evaluate the association among
      posttraumatic growth, dyadic adjustment, and quality of life and to explore the
      predictors affecting quality of life of the couple. METHODS: A cross-sectional
      comparative survey design was utilized. Participants were 57 couples recruited
      from a national cancer center in Korea. Data were analyzed using paired t-test,
      McNemar test and independent t-test. On the basis of variables found to be
      significantly associated with quality of life, multiple regression was used to
      examine the simultaneous influence of multiple predictors. RESULTS: Breast
      cancers survivors and spouses perceived breast cancer as a traumatic event (43.9%
      and 24.6%, respectively). The global quality of life was explained by perception
      as trauma (beta=-19.79) and posttraumatic growth (beta=0.46) in survivors, and
      perception as trauma (beta=-18.81) and dyadic adjustment (beta=0.53) in spouses.
      CONCLUSION: Results suggest that future research should use qualitative methods
      to evaluate why contemplating reasons for cancer contributed to posttraumatic
      growth, examine other potential predictors of quality of life such as dyadic
      adjustment and intimacy, and identify links between posttraumatic growth and
      other psychological outcomes such as distress and well-being, using prospective
      analyses.

PMID- 25381783
TI  - [A predictive model of fall prevention behaviors in postmenopausal women].
AB  - PURPOSE: This study was done to propose and test a predictive model that would
      explain and predict fall prevention behaviors in postmenopausal women. The health
      belief model was the theoretical basis to aid development of a nursing
      intervention fall prevention program. METHODS: Data for 421 postmenopausal women
      were selected from an original data set using a survey design. The structural
      equation model was tested for 3 constructs: modifying factors, expectation
      factors, and threat factors. Expectation factors were measured as relative
      perceived benefit (perceived benefit minus perceived barrier), self-efficacy, and
      health motivation; threat factors, as perceived susceptibility (fear of falling)
      and perceived severity (avoiding activity for fear of falling); and modifying
      factors: level of education and knowledge about fall prevention. Data were
      analyzed using SPSS Windows and AMOS program. RESULTS: Mean age was 55.7 years
      (range 45-64), and 19.7% had experienced a fall within the past year. Fall
      prevention behaviors were explained by expectation and threat factors indicating
      significant direct effects. Mediating effect of health beliefs was significant in
      the relationship between modifying factors and fall prevention behaviors. The
      proposed model explained 33% of the variance. CONCLUSION: Results indicate that
      fall prevention education should include knowledge, expectation, and threat
      factors based on health belief model.

PMID- 25381784
TI  - [Current state of influenza vaccination and factors affecting vaccination rate
      among pregnant women].
AB  - PURPOSE: This study was done to examine the actual state of influenza vaccination
      among pregnant women and factors affecting vaccination rate. METHODS: Data were
      collected using self-report questionnaires. Participants were pregnant women who
      participated in a prenatal education program at an acute care hospital in 2013.
      Data collected from 218 pregnant women were analyzed using the SPSS 18.0 Program.
      RESULTS: Only 48.6% of the pregnant women had received vaccination when the
      influenza was prevalent. Statistically significant factors affecting the
      influenza vaccination rate among pregnant women were vaccination experience in
      the previous year, knowledge and attitude about vaccination, and gestation
      period. CONCLUSION: Results indicate that the influenza vaccination rate among
      pregnant women is lower than that of elders, healthcare workers, and patients
      with chronic diseases, who have been considered to be the mandatory vaccination
      recipients. Therefore, it is necessary to develop programs and policies which
      provide information including safety of vaccines for pregnant women and to induce
      positive attitudes towards vaccination for these women, in order to ultimately
      improve the vaccination rate.

PMID- 25381785
TI  - [Incidence and factors influencing oral mucositis in patients with hematopoietic
      stem cell transplantation].
AB  - PURPOSE: This study was done to examine the incidence of oral mucositis in
      hematopoietic stem cell transplantation patients and to identify factors
      influencing oral mucositis and patient outcomes according to severity. METHODS:
      In this retrospective study, data were collected from electronic medical records
      of 222 patients who had received hematopoietic stem cell transplantation. Oral
      mucositis was evaluated using WHO's assessment scale. Data were analyzed using
      Chi-square test, Fisher exact test, Spearman's correlation, Ordinal logistic
      regression, ANOVA and Kruskal-Wallis test. RESULTS: A total of 69.8% of the
      patients evaluated developed oral mucositis (grade II and over). As a results of
      ordinal regression, factors influencing oral mucositis severity were found to be
      diagnosis, type of transplantation, oxygen inhalation and the number of
      antiemetics administration before transplantation. The severity of oral mucositis
      was found to increase the days of hospitalization, days of TPN administration,
      days of using antibiotics and the number and dosage of analgesics. CONCLUSION:
      The results would help predict severity of oral mucositis in hematopoietic stem
      cell transplantation patients and suggest that provision of appropriate nursing
      assessment and oral care would improve patient outcomes.

PMID- 25381786
TI  - [Predictors of hospitalization for alcohol use disorder in Korean men].
AB  - PURPOSE: This study was done to identify the patterns and significant predictors
      influencing hospitalization of Korean men for alcohol use disorder. METHODS: A
      descriptive study design was utilized. Data were collected using self-report
      questionnaires from 143 inpatients who met the DSM-5 alcohol use disorder
      criteria and were receiving treatment and 157 social drinkers living in the
      community. The questionnaires included Alcohol Use Disorders Identification Test
      (AUDIT), Alcohol Problems, Alcohol Expectancy Questionnaire (AEQ), Life Position,
      and The Korean version of the Children of Alcoholics Screening Test (CAST-K).
      Data were analyzed using descriptive statistics, t-test, chi2-test, F-test,
      Pearson correlation coefficients, and logistic regression with forward stepwise.
      RESULTS: AUDIT had significant correlations with alcohol problems, alcohol
      expectancy, and parents' alcoholism. In logistic regression, factors
      significantly affecting hospitalization were divorced (OR=4.18, 95% CI: 1.28
      13.71), graduation from elementary school (OR=28.50, 95% CI: 8.07-100.69), middle
      school (OR=6.66, 95% CI: 2.21-20.09), high school (OR=6.31, 95% CI: 2.59-15.36),
      drinking alone (OR=9.07, 95% CI: 1.78-46.17), family history of alcoholism
      (OR=2.41, 95% CI: 1.11-5.25), interpersonal relationship problems (OR=1.28, 95%
      CI:1.17-1.41), and sexual enhancement of alcohol expectancy (OR=0.83, 95% CI:
      0.72-0.94), which accounted for 53% of the variance. CONCLUSION: Results suggest
      that interpersonal relationship programs and customized cognitive programs for
      social drinkers in the community are needed to decreased alcohol related
      hospitalization in Korean men.

PMID- 25381787
TI  - [Construct validity of the life transition scale for parents of children with
      autism].
AB  - PURPOSE: The study was done to identify the construct validity and reliability of
      the life transition scale (LTS) for parents who have children with autism.
      METHODS: Exploratory factor analysis (EFA) and confirmative factor analysis (CFA)
      were conducted to identify the most adequate measurement model for structural
      validity. Convergent validity and discriminant validity were also conducted for
      structural validity. Data were collected from 208 parents through self-reported
      questionnaires and analyzed with SPSS/WIN 15.0 and AMOS 20.0 version. RESULTS: A
      four factor-structure was validated (chi2=541.23, p<.001, GFI=.82, RMSEA=.07,
      IFI=.89, CFI=.89, PNFI=.73, Q (chi2/df)=2.20) at the 3rd order of EFA and CFA,
      and factors were named as denying, wandering, despairing, and accepting. Both
      convergent and determinant validity for LTS were 100%. Cronbach's alphas for the
      reliability of each structure were .77-.90 and .83 for total structure.
      CONCLUSION: The four structures, 24-item instrument showed satisfactory
      reliability and validity. LTS has the potential to be appropriate for assessing
      the transition process of life for parents who have children with autism and
      provides basic directions for differentiated support and care at each stage.

PMID- 25381788
TI  - [Risk factors for deliberate self-extubation].
AB  - PURPOSE: This study was conducted to analyze intubation survival rates according
      to characteristics and to identify the risk factors affecting deliberate self
      extubation. METHODS: Data were collected from patients' electronic medical
      reports from one hospital in B city. Participants were 450 patients with
      endotracheal intubation being treated in intensive care units. The collected data
      were analyzed using Kaplan-Meier estimation, Log rank test, and Cox's
      proportional hazards model. RESULTS: Over 15 months thirty-two (7.1%) of the 450
      intubation patients intentionally extubated themselves. The patients who had
      experienced high level of consciousness, agitation. use of sedative, application
      of restraints, and day and night shift had significantly lower intubation
      survival rates. Risk factors for deliberate self-extubation were age (60 years
      and over), unit (neurological intensive care), level of consciousness (higher),
      agitation, application of restraints, shift (night), and nurse-to-patient ratio
      (one nurse caring for two or more patients). CONCLUSION: Appropriate use of
      sedative drugs, effective treatment to reduce agitation, sufficient nurse-to
      patient ratio, and no restraints for patients should be the focus to diminish the
      number of deliberate self-extubations.

PMID- 25381789
TI  - [Effectiveness of a self-management program using goal setting based on a G-AP
      for patients after a stroke].
AB  - PURPOSE: This study was conducted to develop a self-management program using goal
      setting for patients after a stroke. The program was based on a theory-based Goal
      setting and Action Planning framework (G-AP), and the effectiveness of the
      program was examined. METHODS: A non-equivalent control group pretest-posttest
      design was used. The experimental group (n=30) received the self-management
      program using goal setting based on the G-AP over 7 weeks. The education was
      delivered individually with a specifically designed stroke workbook. The control
      group (n=30) received only patient information leaflets about stroke. RESULTS:
      There were significant differences between the two groups. Stroke knowledge, self
      efficacy, and health behavior compliance were significantly higher (all p<.001),
      and hospital anxiety (p<.001) and depression (p<.001) were significantly lower in
      the experimental group compared to the control group. CONCLUSION: This self
      management program using goal setting based on a G-AP was found to be useful and
      beneficial for patients in stroke rehabilitation settings.

PMID- 25381790
TI  - Attempting to prevent postnatal depression by targeting the mother-infant
      relationship: a randomised controlled trial.
AB  - AIM: The purpose of the study was to investigate whether an intervention which
      focused on enhancing the quality of the mother-infant relationship would prevent
      the development of postnatal depression (PND) and the associated impairments in
      parenting and adverse effects on child development. BACKGROUND: Recent meta
      analyses indicate modest preventive effects of psychological treatments for women
      vulnerable to the development of PND. However, given the strong evidence for an
      impact of PND on the quality of the mother-infant relationship and child
      development, it is notable that there are limited data on the impact of
      preventive interventions on these outcomes. This is clearly a question that
      requires research attention. Accordingly, a randomised controlled trial (RCT) was
      conducted of such a preventive intervention. METHODS: A large sample of pregnant
      women was screened to identify those at risk of PND. In an RCT 91 were randomly
      assigned to receive the index intervention from research health visitors, and 99
      were assigned to a control group who received normal care. In an adjacent area 76
      women at risk of PND received the index intervention from trained National Health
      Service (NHS) health visitors. The index intervention involved 11 home visits,
      two antenatally and nine postnatally. They were supportive in nature, with
      specific measures to enhance maternal sensitivity to infant communicative
      signals, including items from the Neonatal Behavioral Assessment Scale.
      Independent assessments were made at 8 weeks, 18 weeks, and 12 and 18 months
      postpartum. Assessments were made of maternal mood, maternal sensitivity in
      mother-infant engagement, and infant behaviour problems, attachment and
      cognition. FINDINGS: The RCT revealed that the index intervention had no impact
      on maternal mood, the quality of the maternal parenting behaviours, or infant
      outcome, although there were suggestions, on some self-report measures, that
      those with a lower level of antenatal risk experienced benefit. This was also the
      case for the intervention delivered by trained NHS health visitors. The findings
      indicate that the approach investigated to preventing PND and its associated
      problems cannot be recommended.

PMID- 25381791
TI  - Aortic insufficiency in patients with sustained left ventricular systolic
      dysfunction after axial flow assist device implantation.
AB  - BACKGROUND: Predicting the occurrence of aortic insufficiency (AI) during left
      ventricular assist device (LVAD) support has remained unsolved. METHODS AND
      RESULTS: We enrolled 52 patients who had received continuous flow LVAD (14 axial
      and 38 centrifugal pumps) and who been followed for >=6 months between Jun 2006
      and Dec 2013. Native aortic valve (AV) opening was observed in 18 patients (35%)
      with improved LV systolic function, and none of them had AI. On multivariate
      logistic regression analysis preoperative shorter heart failure duration was the
      only independent predictor of postoperative native AV opening (P=0.042; odds
      ratio [OR], 0.999). Of the remaining 34 patients (65%) with closed AV, 11 had AI
      with enlargement of the aortic root and narrow pulse pressure. Among those with
      closed AV, axial pump use (n=13) was the only significant predictor of the
      development of AI (P=0.042; OR, 4.950). Patients with AI had lower exercise
      capacity and a higher readmission rate than those without AI during 2-year LVAD
      support (55% vs. 8%; P<0.001). CONCLUSIONS: Native AV opening during LVAD support
      is profoundly associated with reversal of LV systolic function, especially in
      patients with preoperative shorter heart failure duration. Among those in whom
      the native AV remains closed, low pulsatility of axial flow pump may facilitate
      aortic root remodeling and post-LVAD AI development that results in worse
      clinical outcome.

PMID- 25381792
TI  - Subclinical microalbuminuria as a predictor of heart failure prognosis.

PMID- 25381794
TI  - Intimacy and sexuality of nursing home residents with dementia: a systematic
      review.
AB  - BACKGROUND: Considering people with dementia, increasing cognitive, physical, and
      environmental impairments can impede the capacity to express and experience
      intimacy and sexuality. When a move to a residential (nursing) home becomes
      inevitable, increasing dependency can influence this even more. The aim of the
      review is to provide a structured overview of all elements of intimacy across the
      full spectrum of intimacy and sexuality in people with dementia, living in
      specialist residential care. METHODS: A systematic search and review were
      conducted. Research published between 1990 and 2013 was identified in the
      electronic databases: Pubmed, PsychInfo, and Medline. Inclusion and exclusion
      criteria were predefined. Selected studies were assessed on quality, using the
      Mixed METHODS Appraisal Tool. RESULTS: Twelve of the 215 initially retrieved
      unique research publications were selected. A varied range of studies were found;
      these studies differed in design, research quality, searched population, and
      research theme. Different themes emerged: intimate and sexual behavior, knowledge
      and attitudes, capacity to consent and care culture, and staff training and
      guidelines. CONCLUSIONS: Although results were found in a wide range of intimate
      and sexual behavior, knowledge, attitudes and needs of others, and descriptions
      of culture in residential and nursing homes, the perspective of residents was
      lacking in literature. Also a "protective" care paradigm was found throughout.
      Future research is needed to highlight resident perspective and develop training
      opportunities and guidelines for care staff.

PMID- 25381793
TI  - Fragmented QRS predicts heart failure progression in patients with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Although fragmented QRS complex (frag-QRS) reflecting intra
      ventricular conduction delay has been shown to be a prognostic marker for cardiac
      events, few data exist regarding the impact of frag-QRS on cardiac events in
      hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Ninety-four HCM patients
      (56 male; mean age, 58 +/- 17 years) were retrospectively investigated. Frag-QRS
      was defined as the presence of various RsR' patterns in at least 2 contiguous ECG
      leads. Major arrhythmic events (MAE) were defined as sudden cardiac death, and
      combined sustained ventricular tachycardia/ventricular fibrillation. New-onset
      atrial fibrillation (AF) was diagnosed based on ECG during provisional or routine
      medical examination. Heart failure (HF) with hospitalization was defined as
      hospital admission due to subjective or objective symptoms. Frag-QRS was detected
      in 31 patients (33%).TNNI3 was the most frequent disease-causing gene. Median
      follow-up was 4.6 years. The 4-year cumulative survival rates of cardiac death,
      MAE, new-onset AF and HF with hospitalization were 97.6%, 94.6%, 87.5% and 89.3%,
      respectively. On multivariate analysis, frag-QRS was significantly associated
      with HF with hospitalization (adjusted hazard ratios [95% confidence intervals]:
      5.4 [1.2-36], P=0.03). Moreover, HF-free survival was significantly lower in the
      frag-QRS (+) group compared to the frag-QRS (-) group (79.0% vs. 95.1%, P=0.03).
      CONCLUSIONS: Frag-QRS is associated with HF with hospitalization in HCM patients
      who had a unique distribution of gene mutations.

PMID- 25381795
TI  - Insight into the impact of environments on structure of chimera C3 of human beta
      defensins 2 and 3 from molecular dynamics simulations.
AB  - C3 is a chimera from human beta-defensins 2 and 3 and possesses higher
      antimicrobial activity compared with its parental molecules, so it is an
      attractive candidate for clinical application of antimicrobial peptides. In
      continuation with the previous studies, molecular dynamics (MD) simulations were
      carried out for further investigating the effect of ambient environments
      (temperature and bacterial membrane) on C3 dynamics. Our results reveal that C3
      has higher flexibility, larger intensity of motion, and more relevant secondary
      structural changes at 363 K to adapt the high temperature and maintain its
      antimicrobial activity, comparison with it at 293 K; when C3 molecule associates
      with the bacterial membrane, it slightly fluctuates and undergoes local
      conformational changes; in summary, C3 molecule demonstrates stable conformations
      under these environments. Furthermore, MD results analysis show that the
      hydrophobic contacts, the hydrogen bonds, and disulfide bonds in the peptide are
      responsible for maintaining its stable conformation. In addition, our simulation
      shows that C3 peptides can make anionic lipids clustered in the bacterial
      membrane; it means that positive charges and pronounced regional cationic charge
      density of C3 are most key factors for its antimicrobial activity. 

PMID- 25381798
TI  - Diversity characteristics and the experiences of nursing students' during
      clinical placements: A qualitative study of students and supervisors views.
AB  - Abstract Background: Little is known about which diversity characteristics if
      any, impact on nursing students' clinical placements or how these may affect the
      quality of their learning experiences. There is therefore a need to better
      understand these effects not only from the student's perspective but also from
      the perspective of the staff who supervise them, in order to ensure students
      obtain maximal benefit from their placements. Aim: To describe the clinical
      experiences of nursing students and the diversity characteristics that affect
      this learning experience. Methods: Data were collected from a series of open
      ended questions embedded within a larger anonymous web-based survey, from August
      2011 to March 2012. Participants included first, second and third year
      undergraduate Bachelor of Nursing students (N=704) and faculty members involved
      in the clinical learning environment (N = 165) from seven Australian
      universities. Findings: Qualitative findings were clustered into three main
      themes, differences, difficulty and discrimination, each with three subthemes.
      Conclusion: Findings suggest a need to offer appropriate support for nursing
      students who feel different because of diversity characteristics. Whilst some of
      the participant perceptions are confronting they provide valuable insights for
      universities developing curricula and the clinical placement facilities where
      students obtain their experience.

PMID- 25381797
TI  - Trend of telomerase activity change during human iPSC self-renewal and
      differentiation revealed by a quartz crystal microbalance based assay.
AB  - Telomerase plays an important role in governing the life span of cells for its
      capacity to extend telomeres. As high activity of telomerase has been found in
      stem cells and cancer cells specifically, various methods have been developed for
      the evaluation of telomerase activity. To overcome the time-consuming procedures
      and complicated manipulations of existing methods, we developed a novel method
      named Telomeric Repeat Elongation Assay based on Quartz crystal microbalance
      (TREAQ) to monitor telomerase activity during the self-renewal and
      differentiation of human induced pluripotent stem cells (hiPSCs). TREAQ results
      indicated hiPSCs possess invariable telomerase activity for 11 passages on
      Matrigel and a steady decline of telomerase activity when differentiated for
      different periods, which is confirmed with existing golden standard method. The
      pluripotency of hiPSCs during differentiation could be estimated through
      monitoring telomerase activity and compared with the expression levels of markers
      of pluripotency gene via quantitative real time PCR. Regular assessment for
      factors associated with pluripotency or stemness was expensive and requires
      excessive sample consuming, thus TREAQ could be a promising alternative
      technology for routine monitoring of telomerase activity and estimate the
      pluripotency of stem cells. 

PMID- 25381796
TI  - Telomere length and the risk of atrial fibrillation: insights into the role of
      biological versus chronological aging.
AB  - BACKGROUND: Advanced age is the most important risk factor for atrial
      fibrillation (AF); however, the mechanism remains unknown. Telomeres, regions of
      DNA that shorten with cell division, are considered reliable markers of
      biological aging. We sought to examine the association between leukocyte telomere
      length (LTL) and incident AF in a large population-based cohort using direct LTL
      measurements and genetic data. To further explore our findings, we compared
      atrial cell telomere length and LTL in cardiac surgery patients. METHODS AND
      RESULTS: Mean LTL and the TERT rs2736100 single nucleotide polymorphism were
      assessed as predictors of incident AF in the Cardiovascular Health Study (CHS).
      Among the surgical patients, within subject comparison of atrial cell telomere
      length versus LTL was assessed. Among 1639 CHS participants, we observed no
      relationship between mean LTL and incident AF before and after adjustment for
      potential confounders (adjusted hazard ratio, 1.09; 95% confidence interval: 0.92
      1.29; P=0.299); chronologic age remained strongly associated with AF in the same
      model. No association was observed between the TERT rs2736100 single nucleotide
      polymorphism and incident AF (adjusted hazard ratio: 0.95; 95% confidence
      interval: 0.88-1.04; P=0.265). In 35 cardiac surgery patients (26 with AF),
      atrial cell telomere length was longer than LTL (1.19 +/- 0.20 versus 1.02 +/-
      0.25 [T/S ratio], P<0.001), a finding that remained consistent within the AF
      subgroup. CONCLUSIONS: Our study revealed no evidence of an association between
      LTL and incident AF and no evidence of relative atrial cell telomere shortening
      in AF. Chronological aging independent of biological markers of aging is the
      primary risk factor for AF.

PMID- 25381799
TI  - Switching from singlet-oxygen-mediated oxidation to free-radical-mediated
      oxidation in the pathogenesis of type 2 diabetes in model mouse.
AB  - Oxidative stress plays a key role in the development of type 2 diabetes. However,
      it is still unknown what kind of oxidative stress underlies the development of
      type 2 diabetes. We investigated hydroxyoctadecadienoic acid (HODE) isomers,
      which have been proposed as a biomarker for evaluating oxidative stress in vivo,
      during the development of diabetes in Tsumura Suzuki Obese Diabetes (TSOD) mouse,
      a type 2 diabetes model. It was revealed that glucose tolerance and insulin
      resistance index HOMA-IR in TSOD mice at 5 weeks of age were approximately
      normal, namely, the mice were in the prediabetic state, but these levels were
      significantly exacerbated from 8 weeks of age compared with those in Tsumura
      Suzuki Non Obesity (TSNO) mice (control). Concomitantly, the plasma levels of
      free-radical-mediated oxidation products, 9- and 13-(E,E)-HODE and 7beta
      hydroxycholesterol, in TSOD mice were significantly higher than those in TSNO
      mice at 8, and 8 and 11 weeks of age, respectively. Interestingly, the plasma
      levels of 10- and 12-(Z,E)-HODE, which are produced specifically by singlet
      oxygen-mediated oxidation, in TSOD mice were higher than those in TSNO mice only
      at 5 weeks of age, and not at 8, 11, and 13 weeks of age. We demonstrated that
      singlet-oxygen-mediated oxidation occurred in TSOD mice before development of the
      diabetic phenotypes, including impaired glucose tolerance and insulin resistance.
      These results suggest that excessive singlet-oxygen-mediated oxidation plays an
      important role in the pathogenesis of type 2 diabetes.

PMID- 25381802
TI  - Triiodothyronine as a therapeutic candidate for cardiac metabolism in the failing
      heart.

PMID- 25381800
TI  - Free radical oxidation of cholesterol and its precursors: Implications in
      cholesterol biosynthesis disorders.
AB  - Free radical oxidation of cholesterol and its precursors contribute significantly
      to the pathophysiology of a number of human diseases. This review intends to
      summarize recent developments and provide a perspective on the reactivities of
      sterols toward free radical oxidation, the free radical reaction mechanism, and
      the biological consequences of oxysterols derived from the highly oxidizable
      cholesterol precursor, 7-dehydrocholesterol. We propose that the rigid
      structures, additional substituents on the double bonds, and the well-aligned
      reactive C-H bonds in sterols make them more prone to free radical oxidation than
      their acyclic analogs found in unsaturated fatty acids. The mechanism of sterol
      peroxidation follows some well-established reaction pathways found in the free
      radical peroxidation of polyunsaturated fatty acids, but sterols also undergo
      some reactions that are unique to these compounds. Peroxidation of 7
      dehydrocholesterol gives arguably the most diverse set of oxysterol products that
      have been observed to date. The metabolism of these oxysterols in cells and the
      biological consequences of their formation will be discussed in the context of
      the pathophysiology of the human disease Smith-Lemli-Opitz syndrome. Considering
      the high reactivity of sterols, we propose that a number of other cholesterol
      biosynthesis disorders may be associated with oxidative stress. 

PMID- 25381801
TI  - Case-control estimation of the impact of oncolytic adenovirus on the survival of
      patients with refractory solid tumors.
AB  - Oncolytic immunotherapy with cytokine armed replication competent viruses is an
      emerging approach in cancer treatment. In a recent randomized trial, an increase
      in response rate was seen but the effect on overall survival is not known with
      any virus. To facilitate randomized trials, we performed a case-control study
      assessing the survival of 270 patients treated in an Advanced Therapy Access
      Program (ATAP), in comparison to matched concurrent controls from the same
      hospital. The overall survival of all virus treated patients was not increased
      over controls. However, when analysis was restricted to GMCSF-sensitive tumor
      types treated with GMSCF-coding viruses, a significant improvement in median
      survival was present (from 170 to 208 days, P = 0.0012, N = 148). An even larger
      difference was seen when analysis was restricted to good performance score
      patients (193 versus 292 days, P = 0.034, N = 90). The survival of ovarian cancer
      patients was especially promising as median survival nearly quadrupled (P =
      0.0003, N = 37). These preliminary data lend support to initiation of randomized
      clinical trials with GMCSF-coding oncolytic adenoviruses. 

PMID- 25381803
TI  - Helper T cell diversity and plasticity.

PMID- 25381804
TI  - Serum heart-type fatty acid-binding protein level can be used to detect acute
      kidney injury on admission and predict an adverse outcome in patients with acute
      heart failure.
AB  - BACKGROUND: Different mechanisms of acute kidney injury (AKI) may exist for acute
      heart failure (AHF) patients compared with other patients. METHODS AND RESULTS:
      We analyzed data from 282 patients with AHF. The biomarkers were measured within
      30 min of admission. Patients were assigned to a no-AKI (n=213) or AKI group
      (Class R (n=49), Class I (n=15) or Class F (n=5)) using the RIFLE classifications
      on admission. We evaluated the relationships between the biomarkers and AKI, in
      hospital mortality, all-cause death and HF events (HF re-admission, all-cause
      death) within 90 days. The serum heart-type fatty acid-binding protein (s-HFABP)
      levels were significantly higher in the AKI than in the no-AKI group, and the
      predictive biomarker for AKI was s-HFABP (odds ratio: 6.709; 95% confidence
      interval: 3.362-13.391). s-HFABP demonstrated an optimal balance between
      sensitivity and specificity (71.0%, 79.3%; area under the receiver-operating
      characteristic curve [AUC]=0.790) at 22.8 ng/ml for AKI, at 22.8 ng/ml for Class
      I/F (90.0%, 71.4%; AUC=0.836) and at 21.0 ng/ml for in-hospital mortality (74.3%,
      70.0%; AUC=0.726). The Kaplan-Meier survival curves showed a significantly poorer
      prognosis in the high s-HFABP group (>=22.9 ng/ml) than in other groups.
      CONCLUSIONS: The s-HFABP level can indicate AKI on admission, and a high s-HFABP
      level is associated with a poorer prognosis for AHF patients.

PMID- 25381806
TI  - Local photo-oxidation of individual single walled carbon nanotubes probed by
      femtosecond four wave mixing imaging.
AB  - Photo-oxidation of individual, air-suspended single walled carbon nanotubes
      (SWCNTs) is studied by femtosecond laser spectroscopy and imaging. Individual
      SWCNTs are imaged by four wave mixing (FWM) microscopy under an inert gas (Ar or
      N2) atmosphere. When imaging is performed in an ambient air atmosphere, the decay
      of the FWM signal takes place. Electron microscopy shows that SWCNTs are not
      destroyed and the process is attributed to photoinduced oxidation reactions which
      proceed via a non-linear excitation mechanism, when irradiation is performed with
      ~30 fs pulses in the visible spectral region (500-600 nm). Photo-oxidation can be
      localized in specific regions of SWCNTs within optical resolution (~300 nm). The
      effect of photo-oxidation on Raman spectra was studied by irradiating a local
      spot on an individual SWCNT and comparing the spectra of irradiated and non
      irradiated regions of the same tube. It is shown at an individual nanotube level
      that oxidation leads to a decrease of the intensity of the Raman signal and an
      upshift of the G-band. 

PMID- 25381805
TI  - Development and implementation challenges of a quality assured HIV infant
      diagnosis program in Nigeria using dried blood spots and DNA polymerase chain
      reaction.
AB  - Nigeria has one of the highest HIV burdens as well as mother-to-infant
      transmission rates in the world. A pilot program using polymerase chain reaction
      (PCR)-based testing of dried blood spot (DBS) specimens was implemented to enable
      early identification of HIV-infected infants and timely referral and linkage to
      care. From February 2007 to October 2008, whole blood was collected by finger
      prick to prepare DBS from infants <18 months presenting in six public mother-and
      child health facilities in Lagos, Nigeria. The DBS were tested using the Roche
      Amplicor HIV-1 DNA Test, v1.5. To monitor laboratory testing quality, all of the
      PCR-positive and 10% of the PCR-negative DBS were retested by the same method at
      another reference laboratory. Three hundred and sixty-five randomly selected
      infants were screened using HIV rapid tests (RT) according to the national
      algorithm and RT-negative and PCR-positive specimens were also tested using
      Genscreen enzyme-linked immunosorbent assay (EIA) (Bio-Rad, France). The
      turnaround time (TAT) from sample collection, testing, and dispatching of results
      from each health facility was monitored. A total of 1,273 infants with a median
      age of 12.6 weeks (1 day to 71.6 weeks) participated in the program and 280
      (22.0%) were PCR positive. HIV transmission levels varied greatly in the
      different health facilities ranging from 7.1% to 38.4%. Infants aged 48 to 72
      weeks had the highest level of PCR positivity (41.1%). All PCR-positive specimens
      were confirmed by retesting. The mean turnaround time from DBS collection to
      returning of the laboratory result to the health facilities was 25 days. Three
      infants were found to be HIV antibody negative by rapid tests but were positive
      by both PCR and the fourth generation EIA. The DBS-based PCR program accurately
      identified all of the HIV-infected infants. However, many programmatic challenges
      related to the laboratory and TAT were identified.

PMID- 25381807
TI  - The clinical syndrome of BRD: what it is and what it is not.
AB  - The clinical syndrome of bovine respiratory disease (BRD) continues to be a major
      challenge in bovine production systems. We are challenged by our ability to
      predict morbidity in groups of cattle, our ability to accurately diagnose and
      provide a prognosis for individual cases, and our ability to evaluate the results
      of preventive and therapeutic interventions in the field when production system
      data are the sole basis for analysis. However, we are fortunate to have perhaps
      the highest quantity and quality of negative-controlled, prospective, randomized,
      and masked clinical trial data for any disease in veterinary medicine. It is
      nevertheless important to recognize that case definitions in these studies may
      not be consistent or necessarily externally relevant, and that production data in
      these studies are often missing. 

PMID- 25381808
TI  - Cluster-controlled dimerisation in supramolecular ruthenium photosensitizer
      polyoxometalate systems.
AB  - A supramolecular reaction system is reported where a labile molecular metal oxide
      cluster enables the unprecedented dimerisation of ruthenium photosensitizers
      [Ru(L)2(tmbiH2)](2+) (L = 4,4'-di-tert-butyl-2,2'-bipyridine (1a) or 2,2'
      bipyridine (1b); tmbiH2 = 5,5',6,6'-tetramethyl-2,2'-bibenzimidazole). In the
      presence of [Mo8O26](4-) clusters (2) the dimerisation is triggered by the in
      situ conversion of [Mo8O26](4-) to [Mo6O19](2-) which results in the release of
      hydroxide ions. Simultaneous deprotonation of the pH-sensitive tmbiH2-ligands
      starts the dimerisation, resulting in the formation of the dinuclear complex
      [(Ru(L)2)2(tmbi)](2+) (L = 4,4'-di-tert-butyl-2,2'-bipyridine (3) or 2,2'
      bipyridine (4)). The dimerisation reaction can be suppressed when 2 is replaced
      by a stable polyoxomolybdate cluster, [Mo5O15(PhPO3)2](4-) (5) and the reaction
      between 1a and 5 leads to the formation of hydrogen-bonded supramolecular
      aggregates 6. The solution and solid-state interactions in these systems were
      investigated using a range of spectroscopic and crystallographic techniques and
      compounds 3, 4 and 6 were characterized using single-crystal XRD.

PMID- 25381809
TI  - Efficacy of alpha-lipoic acid in diabetic neuropathy.
AB  - INTRODUCTION: Neuropathy is a serious complication of diabetes. Its management
      focuses on glycaemic control, multifactorial cardiovascular risk intervention,
      pathogenesis-oriented therapy, and analgesics where needed. AREAS COVERED: The
      objective of this review is assessment of efficacy and safety of alpha lipoic
      acid (ALA, also thioctic acid) in pathogenesis-oriented treatment of diabetic
      neuropathy. The mechanisms of action of ALA in experimental diabetic neuropathy
      include reduction of oxidative stress along with improvement in nerve blood flow,
      nerve conduction velocity, and several other measures of nerve function. There is
      ample evidence from randomised, double-blind, placebo-controlled clinical trials
      and meta-analyses, suggesting that ALA is efficacious and safe for the diabetic
      neuropathy, accomplishing clinically meaningful improvements. EXPERT OPINION: ALA
      is a valuable therapeutic option for diabetic neuropathy. When compared with
      currently licensed analgesic drugs, it is better tolerated, has a more rapid
      onset of action, and improves paraesthesiae, numbness, sensory deficits, and
      muscle strength in addition to neuropathic pain. In clinical practice, ALA may be
      chosen in patients with early neuropathic deficits and symptoms, in whom clinical
      improvement is more likely. ALA should also be considered when comorbidities
      render other analgesics less appropriate or in the presence of cardiovascular
      autonomic neuropathy.

PMID- 25381810
TI  - Caring for caregivers after a stroke.

PMID- 25381812
TI  - Sub-20 nm-Fe3O4 square and circular nanoplates: synthesis and facet-dependent
      magnetic and electrochemical properties.
AB  - We present an effective method to synthesize 15 nm magnetite nanocrystals with
      the morphology of square and circular nanoplates, which expose (001) facet and
      (111) facet, respectively. The magnetic property and electrochemical behavior
      towards As(III) exhibit strong facet-dependent characteristics. Theoretical
      calculations confirm the facet-dependent characteristics and provide the
      corresponding explanations.

PMID- 25381811
TI  - Enhanced frequency and potential mechanism of B regulatory cells in patients with
      lung cancer.
AB  - BACKGROUND: Regulatory T cells (Tregs) and B cells (Bregs) play an important role
      in the development of lung cancer. The present study aimed to investigate the
      phenotype of circulating Tregs and Bregs in patients with lung cancer and explore
      potential mechanism by which lung cancer cells act on the development of both.
      METHODS: Patients with lung cancer (n = 268) and healthy donors (n = 65) were
      enrolled in the study. Frequencies of Tregs and Bregs were measured by flow
      cytometry with antibodies against CD4, CD25, CD127, CD45RA, CD19, CD24, CD27 and
      IL-10 before and after co-cultures. qRT-PCR was performed to evaluate the mRNA
      levels of RANTES, MIP-1alpha, TGF-beta, IFN-gamma and IL-4. RESULTS: We found a
      lower frequency of Tregs and a higher frequency of Bregs in patients with lung
      cancer compared to healthy donors. Co-culture of lung cancer cells with
      peripheral blood mononuclear cells could polarize the lymphocyte phenotype in the
      similar pattern. Lipopolysaccharide (LPS)-stimulated lung cancer cells
      significantly modulated regulatory cell number and function in an in vitro model.
      CONCLUSION: We provide initial evidence that frequencies of peripheral Tregs
      decreased or Bregs increased in patients with lung cancer, which may be modulated
      directly by lung cancer cells. It seems cancer cells per se plays a crucial role
      in the development of tumor immunity.

PMID- 25381813
TI  - How good can CVD-grown monolayer graphene be?
AB  - Chemical vapor deposition (CVD) is considered the most promising method for
      pushing graphene into commercial products. However, CVD grown graphene is usually
      of low quality. In this work we explore how good can CVD-derived monolayer
      graphene be. Through the combinational optimization of the main processes of
      growth, transfer, device fabrication and measurements, we show that the optimized
      CVD graphene can present performance comparable to mechanical exfoliated ones: in
      particular, high carrier mobility at room temperature on the Si/SiO2 substrate,
      perfect electron-hole symmetry and excellent uniformity (the mobility ranged from
      5000 to 12,000 cm(2) V(-1) s(-1) with an average mobility of ~ 8800 cm(2) V(-1)
      s(-1) and 50% were higher than 10,000 cm(2) V(-1) s(-1)). In addition we found
      that the adsorbed oxygen and water molecules on graphene lead to p-type doping in
      graphene, and transferred charges bring charged impurity scattering to the
      transporting carriers in the graphene channel. It is therefore necessary to carry
      out electrical measurements under vacuum to obtain high intrinsic carrier
      mobility CVD grown graphene.

PMID- 25381814
TI  - STIM1 overexpression promotes colorectal cancer progression, cell motility and
      COX-2 expression.
AB  - Tumor metastasis is the major cause of death among cancer patients, with >90% of
      cancer-related death attributable to the spreading of metastatic cells to
      secondary organs. Store-operated Ca(2+) entry (SOCE) is the predominant Ca(2+)
      entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1)
      is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here
      we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients.
      STIM1 overexpression in CRC was significantly associated with tumor size, depth
      of invasion, lymph node metastasis status and serum levels of carcinoembryonic
      antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility,
      while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our
      data further suggested that STIM1 promoted CRC cell migration through increasing
      the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2
      (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to
      rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2
      with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In
      short, our data provided clinicopathological significance for STIM1 and SOCE in
      CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC
      metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated
      metastasis with COX-2 inhibitors. 

PMID- 25381816
TI  - Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted
      therapeutic strategy in prostate cancer.
AB  - Angiogenesis is required for tumour growth and is induced principally by vascular
      endothelial growth factor A (VEGF-A). VEGF-A pre-mRNA is alternatively spliced at
      the terminal exon to produce two families of isoforms, pro- and anti-angiogenic,
      only the former of which is upregulated in prostate cancer (PCa). In renal
      epithelial cells and colon cancer cells, the choice of VEGF splice isoforms is
      controlled by the splicing factor SRSF1, phosphorylated by serine-arginine
      protein kinase 1 (SRPK1). Immunohistochemistry staining of human samples revealed
      a significant increase in SRPK1 expression both in prostate intra-epithelial
      neoplasia lesions as well as malignant adenocarcinoma compared with benign
      prostate tissue. We therefore tested the hypothesis that the selective
      upregulation of pro-angiogenic VEGF in PCa may be under the control of SRPK1
      activity. A switch in the expression of VEGF165 towards the anti-angiogenic
      splice isoform, VEGF165b, was seen in PC-3 cells with SRPK1 knockdown (KD). PC-3
      SRPK1-KD cells resulted in tumours that grew more slowly in xenografts, with
      decreased microvessel density. No effect was seen as a result of SRPK1-KD on
      growth, proliferation, migration and invasion capabilities of PC-3 cells in
      vitro. Small-molecule inhibitors of SRPK1 switched splicing towards the anti
      angiogenic isoform VEGF165b in PC-3 cells and decreased tumour growth when
      administered intraperitoneally in an orthotopic mouse model of PCa. Our study
      suggests that modulation of SRPK1 and subsequent inhibition of tumour
      angiogenesis by regulation of VEGF splicing can alter prostate tumour growth and
      supports further studies for the use of SRPK1 inhibition as a potential anti
      angiogenic therapy in PCa. 

PMID- 25381815
TI  - FOXC2 promotes colorectal cancer metastasis by directly targeting MET.
AB  - Metastasis is the major cause of death in colorectal cancer (CRC). Although
      multiple genes have been identified to be responsible for the development of CRC,
      the molecular changes that enable CRC cells to undergo early local invasion and
      to form distant metastatic colonies still remain largely unknown. Herein, we
      investigated the role of Forkhead box protein C2 (FOXC2) and explored the
      underlying mechanisms in invasion and metastasis of CRC. We show that both high
      FOXC2 expression and nuclear localization of FOXC2 are significantly correlated
      with advanced TNM (T=primary tumor; N=regional lymph nodes; M=distant metastasis)
      stages. FOXC2 enhanced the invasive abilities of CRC cells in vitro and promoted
      local invasion and distant metastasis in an orthotopic mouse metastatic model of
      CRC. Microarray analysis revealed that overexpression of FOXC2 increased the
      proto-oncogene MET tyrosine kinase expression and activated the hepatocyte growth
      factor (HGF)-MET signaling pathway. Furthermore, luciferase reporter assays and
      chromatin immunoprecipitation assays revealed that FOXC2 directly associated with
      MET promoter to increase the transcriptional activity of MET. Inhibition of MET
      attenuates the invasive phenotype and metastatic potential of FOXC2
      overexpressing CRC cells, indicating that MET is a major mediator of FOXC2
      promoted metastasis. In addition, FOXC2 expression was positively correlated with
      MET expression in CRC tissue samples. Our findings suggest that FOXC2 has a
      crucial role in CRC metastasis by regulating HGF-MET signaling via inducing MET
      expression, highlighting FOXC2 as a potential therapeutic target for preventing
      or reducing metastasis in CRC. 

PMID- 25381817
TI  - Loss of giant obscurins from breast epithelium promotes epithelial-to-mesenchymal
      transition, tumorigenicity and metastasis.
AB  - Obscurins, encoded by the single OBSCN gene, are giant cytoskeletal proteins with
      structural and regulatory roles. The OBSCN gene is highly mutated in different
      types of cancers. Loss of giant obscurins from breast epithelial cells confers
      them with a survival and growth advantage, following exposure to DNA-damaging
      agents. Here we demonstrate that the expression levels and subcellular
      distribution of giant obscurins are altered in human breast cancer biopsies
      compared with matched normal samples. Stable clones of non-tumorigenic MCF10A
      cells lacking giant obscurins fail to form adhesion junctions, undergo epithelial
      to-mesenchymal transition and generate >100-MUm mammospheres bearing markers of
      cancer-initiating cells. Obscurin-knockdown MCF10A cells display markedly
      increased motility as a sheet in 2-dimensional (2D) substrata and individually in
      confined spaces and invasion in 3D matrices. In line with these observations,
      actin filaments redistribute to extending filopodia where they exhibit increased
      dynamics. MCF10A cells that stably express the K-Ras oncogene and obscurin short
      hairpin RNA (shRNA), but not scramble control shRNA, exhibit increased primary
      tumor formation and lung colonization after subcutaneous and tail vein
      injections, respectively. Collectively, our findings reveal that loss of giant
      obscurins from breast epithelium results in disruption of the cell-cell contacts
      and acquisition of a mesenchymal phenotype that leads to enhanced tumorigenesis,
      migration and invasiveness in vitro and in vivo. 

PMID- 25381819
TI  - Iterative tyrosine phosphorylation controls non-canonical domain utilization in
      Crk.
AB  - Crk, the prototypical member of a class of Src homology-2 (SH2) and Src homology
      3 (SH3) domain containing proteins that controls the coordinated assembly of
      signaling complexes, is regulated by phosphorylation of Y221 in the linker
      region, which forms an intramolecular SH2-pY221 auto-clamp to interrupt SH2-N
      terminal SH3 domain (SH3N) signaling. Here, we show using LC-MS/MS and by
      generating phospho-specific antibodies that, iteratively with Y221, the Crk C
      terminal SH3 domain (SH3C) is routinely phosphorylated on Y239 and/or Y251 by
      several extracellular stimuli known to engage Crk. Although phosphorylation at
      Y221 auto-inhibits the Crk SH2, phosphorylation of the SH3C generates an
      unconventional phosphoSH3C-SH3N unit in which the SH3N is fully functional to
      bind polyproline type II ligands and the phosphoSH3C binds de novo to other SH2
      domains. Using high-throughput SH2 domain profiling, artificial neural network
      and position-specific scoring matrix-based bioinformatics approaches, and
      unbiased mass spectometry, we found that the phosphoSH3C binds several SH2 domain
      containing proteins, including specific non-receptor tyrosine kinases-Abl via
      pY251 and C-terminal Src kinase via pY239. Functionally, we show that the
      phosphoSH3C modulates the Abl-mediated phenotypes of cell spreading and motility.
      Together, these studies describe a versatile mechanism wherein phosphorylation of
      Crk at Y221 is not an off switch but redirects signaling from the SH2-SH3N axis
      to a phosphoSH3C-SH3N axis, with the SH3N as a common denominator. 

PMID- 25381820
TI  - Impairment of antioxidant defense via glutathione depletion sensitizes acute
      lymphoblastic leukemia cells for Smac mimetic-induced cell death.
AB  - Evasion of apoptosis in pediatric acute lymphoblastic leukemia (ALL) is linked to
      aberrant expression of inhibitor of apoptosis (IAP) proteins and dysregulated
      redox homeostasis, rendering leukemic cells vulnerable to redox-targeting
      therapies. Here we discover that inhibition of antioxidant defenses via
      glutathione (GSH) depletion by buthionine sulfoximine (BSO) primes ALL cells for
      apoptosis induced by the Smac mimetic BV6 that antagonizes IAP proteins.
      Similarly, BSO cooperates with BV6 to induce cell death in patient-derived
      primary leukemic samples, underscoring the clinical relevance. In contrast, BSO
      does not sensitize non-malignant lymphohematopoietic cells from healthy donors
      toward BV6, pointing to some tumor selectivity. Mechanistically, both agents
      cooperate to stimulate reactive oxygen species (ROS) production, which is
      required for BSO/BV6-induced cell death, as ROS inhibitors (that is, N
      acetylcysteine, MnTBAP, Trolox) significantly rescue cell death. Further, BSO and
      BV6 cooperate to trigger lipid peroxidation, which is necessary for cell death,
      as genetic or pharmacological blockage of lipid peroxidation by GSH peroxidase 4
      (GPX4) overexpression or alpha-tocopherol significantly inhibits BSO/BV6-mediated
      cell death. Consistently, GPX4 knockdown or GPX4 inhibitor RSL3 enhances lipid
      peroxidation and cell death by BSO/BV6 cotreatment. The discovery of redox
      regulation of Smac mimetic-induced cell death has important implications for
      developing rational Smac mimetic-based combination therapies.

PMID- 25381818
TI  - FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and
      embryonic signalling pathways in cancer.
AB  - Tumour heterogeneity is a major factor undermining the success of therapies
      targeting metastatic cancer. Two major theories are thought to explain the
      phenomenon of heterogeneity in cancer--clonal evolution and cell plasticity. In
      this review, we examine a growing body of work implicating the transcription
      factor FOS-related antigen 1 (FRA-1) as a central node in tumour cell plasticity
      networks, and discuss mechanisms regulating its activity in cancer cells. We also
      discuss evidence from the FRA-1 perspective supporting the notion that clonal
      selection and cell plasticity represent two sides of the same coin. We propose
      that FRA-1-overexpressing clones featuring high plasticity undergo positive
      selection during consecutive stages of multistep tumour progression. This model
      underscores a potential mechanism through which tumour cells retaining elevated
      levels of plasticity acquire a selective advantage over other clonal populations
      within a tumour.

PMID- 25381821
TI  - Wip1 phosphatase in breast cancer.
AB  - Understanding the factors contributing to tumor initiation, progression and
      evolution is of paramount significance. Among them, wild-type p53-induced
      phosphatase 1 (Wip1) is emerging as an important oncogene by virtue of its
      negative control on several key tumor suppressor pathways. Originally discovered
      as a p53-regulated gene, Wip1 has been subsequently found amplified and more
      recently mutated in a significant fraction of human cancers including breast
      tumors. Recent development in the field further uncovered the utility of anti
      Wip1-directed therapies in delaying tumor onset or in reducing the tumor burden.
      Furthermore, Wip1 could be an important factor that contributes to tumor
      heterogeneity, suggesting that its inhibition may decrease the rate of cancer
      evolution. These effects depend on several signaling pathways modulated by Wip1
      phosphatase in a spatial and temporal manner. In this review we discuss the
      recent development in understanding how Wip1 contributes to tumorigenesis with
      its relevance to breast cancer. 

PMID- 25381822
TI  - Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ
      and decreasing Cyr61 expression.
AB  - Lung cancer is the leading cause of cancer death worldwide, with metastasis
      underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has
      been shown to interact with oncogenic Yes-associated protein/transcriptional co
      activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential
      role in tumor progression. However, the functional role of AMOT in lung cancer
      remains unknown. This study aimed to identify the patho-physiological
      characteristics of AMOT in lung cancer progression. Results revealed that AMOT
      expression was significantly decreased in clinical lung cancer specimens.
      Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated
      cancer proliferation, migration, invasion and epithelial-mesenchymal transition.
      The trigger of cancer progression caused by AMOT loss was transduced by decreased
      cytoplasmic sequestration and increased nuclear translocation of oncogenic co
      activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61.
      Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent.
      Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma
      in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer
      metastasis and highlight its critical role as a tumor suppressor and its
      potential as a prognostic biomarker and therapeutic target for lung cancer.

PMID- 25381824
TI  - Intravital imaging of SRF and Notch signalling identifies a key role for EZH2 in
      invasive melanoma cells.
AB  - The acquisition of cell motility is an early step in melanoma metastasis. Here we
      use intravital imaging of signalling reporter cell-lines combined with genome
      wide transcriptional analysis to define signalling pathways and genes associated
      with melanoma metastasis. Intravital imaging revealed heterogeneous cell
      behaviour in vivo: <10% of cells were motile and both singly moving cells and
      streams of cells were observed. Motile melanoma cells had increased Notch- and
      SRF-dependent transcription. Subsequent genome-wide analysis identified an
      overlapping set of genes associated with high Notch and SRF activity. We
      identified EZH2, a histone methyltransferase in the Polycomb repressive complex
      2, as a regulator of these genes. Heterogeneity of EZH2 levels is observed in
      melanoma models, and co-ordinated upregulation of genes positively regulated by
      EZH2 is associated with melanoma metastasis. EZH2 was also identified as
      regulating the amelanotic phenotype of motile cells in vivo by suppressing
      expression of the P-glycoprotein Oca2. Analysis of patient samples confirmed an
      inverse relationship between EZH2 levels and pigment. EZH2 targeting with siRNA
      and chemical inhibition reduced invasion in mouse and human melanoma cell lines.
      The EZH2-regulated genes KIF2C and KIF22 are required for melanoma cell invasion
      and important for lung colonization. We propose that heterogeneity in EZH2 levels
      leads to heterogeneous expression of a cohort of genes associated with motile
      behaviour including KIF2C and KIF22. EZH2-dependent increased expression of these
      genes promotes melanoma cell motility and early steps in metastasis. 

PMID- 25381825
TI  - Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor-suppressive role
      in pancreatic ductal adenocarcinoma.
AB  - Using integrative genomics and functional screening, we identified coiled-coil
      domain containing 68 (CCDC68) as a novel putative tumor suppressor gene (TSG) in
      pancreatic ductal adenocarcinoma (PDAC). CCDC68 allelic losses were documented in
      48% of primary PDAC patient tumors, 50% of PDAC cell lines and 30% of primary
      patient derived xenografts. We also discovered a single nucleotide polymorphism
      (SNP) variant (SNP rs1344011) that leads to exon skipping and generation of an
      unstable protein isoform CCDC68Delta(69-114) in 31% of PDAC patients.
      Overexpression of full length CCDC68 (CCDC68(wt)) in PANC-1 and Hs.766T PDAC cell
      lines lacking CDCC68 expression decreased proliferation and tumorigenicity in
      scid mice. In contrast, the downregulation of endogenous CCDC68 in MIAPaca-2
      cells increased tumor growth rate. These effects were not observed with the
      deletion-containing isoform, CCDC68Delta(69-114). 

PMID- 25381823
TI  - A balancing act: orchestrating amino-truncated and full-length p73 variants as
      decisive factors in cancer progression.
AB  - p73 is the older sibling of p53 and mimics most of its tumor-suppressor
      functions. Through alternative promoter usage and splicing, the TP73 gene
      generates more than two dozen isoforms of which N-terminal truncated DNp73
      variants have a decisive role in cancer pathogenesis as they outweigh the
      positive effects of full-length TAp73 and p53 in acting as a barrier to tumor
      development. Beyond the prevailing view that DNp73 predominantly counteract cell
      cycle arrest and apoptosis, latest progress indicates that these isoforms acquire
      novel functions in epithelial-to-mesenchymal transition, metastasis and therapy
      resistance. New insight into the mechanisms underlying this behavior reinforced
      the expectation that DNp73 variants contribute to aggressive cellular traits
      through both loss of wild-type tumor-suppressor activity and gain-of-function,
      suggesting an equally important role in cancer progression as mutant p53. In this
      review, we describe the novel properties of DNp73 in the invasion metastasis
      cascade and outline the comprehensive p73 regulatome with an emphasis on
      molecular processes putting TAp73 out of action in advanced tumors. These
      intriguing insights provoke a new understanding of the acquisition of aggressive
      traits by cancer cells and may help to set novel therapies for a broad range of
      metastatic tumors. 

PMID- 25381827
TI  - Conventional Cisplatin-Based Combination Chemotherapy Is Effective in the
      Treatment of Metastatic Spermatocytic Seminoma with Extensive
      Rhabdomyosarcomatous Transformation.
AB  - A 52-year-old man was presented with a huge left testicular mass and palpable
      cervical lymphadenopathy with retroperitoneal lymph node enlargement on an
      abdominal computed tomography. A left radical orchiectomy and an ultrasound
      guided neck node biopsy were performed. A pathological examination revealed
      spermatocytic seminoma with extensive rhabdomyosarcomatous transformation, a
      condition known to be highly resistant to platinum-based chemotherapy. The
      patient received four cycles of etoposide, ifosfamide and cisplatin (VIP)
      chemotherapy. A repeat computed tomography revealed a substantial regression
      consistent with a partial response. Retroperitoneal lymph node dissection was
      attempted, which revealed rhabdomyosarcoma; however, complete microscopic
      resection was not achieved. After surgery, the residual abdominal lymph node
      progressed and salvage paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy
      was employed, which again achieved a partial response. Here, we present a first
      case report of a spermatocytic seminoma with extensive rhabdomyosarcomatous
      transformation and multiple metastatic lymphadenopathies that showed a favorable
      response to platinum-based systemic chemotherapy. 

PMID- 25381826
TI  - An Unusual Presentation of Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma
      as Diffuse Pulmonary Infiltrates with Spontaneous Regression.
AB  - A 57-year-old woman presented with cough and dyspnea for 2 months. Computed
      tomography of the chest showed diffuse ground-glass opacities in both lungs.
      Histologic examination via thoracoscopic lung biopsy revealed atypical
      lymphoproliferative lesion. Her symptoms and radiologic findings of the chest
      improved just after lung biopsy without any treatment. Therefore, she was
      discharged and monitored at an outpatient clinic. Two months later, pulmonary
      mucosa-associated lymphoid tissue (MALT) lymphoma was confirmed by the detection
      of API2-MALT1 translocation in fluorescent in situ hybridization analysis.
      Although the lung lesions resolved spontaneously, she received chemotherapy due
      to bone marrow involvement in her staging workup. Pulmonary MALT lymphoma is
      rare. Nodular or consolidative patterns are the most frequent radiologic
      findings. Although the disease has an indolent growth, it rarely resolves without
      treatment. We report an unusual case of pulmonary MALT lymphoma with diffuse
      interstitial abnormalities on image and spontaneous regression on clinical
      course. 

PMID- 25381828
TI  - The clinical impact of 21-gene recurrence score on treatment decisions for
      patients with hormone receptor-positive early breast cancer in Korea.
AB  - PURPOSE: The 21-gene (Oncotype DX) recurrence score (RS) assay is useful in
      predicting the benefits of adjuvant chemotherapy for early breast cancer patients
      and is widely used in Western countries. However, to date, it has not gained much
      popularity in East Asia. We analyzed the results from five institutions'
      experience from using the 21-gene assay and examined the impact of assay results
      on decision making of chemotherapy in Korean breast cancer patients and the
      associations between RS and clinicopathologic characteristics. MATERIALS AND
      METHODS: The 21-gene assay was performed on 212 patients with estrogen receptor
      positive early breast cancer in five institutions. Each center made systemic
      treatment decisions both before and after the knowledge of assay results.
      RESULTS: Among the 212 patients, 132 (62.3%) had a low RS of < 18, 60 (28.3%) had
      an intermediate RS of 18-30, and 20 (9.4%) had a high RS of >= 31. Histologic
      grade, presence of micrometastases, Ki-67, and presence of lymphatic invasion
      were statistically associated with the RS results. Treatment decisions were
      changed in 115 of 212 patients (54.2%) in 109 of 212 (51.4%) from chemotherapy
      plus hormone therapy to hormone therapy, and in six of 212 (2.8%) from hormone
      therapy to chemotherapy plus hormone therapy. CONCLUSION: The 21-gene breast
      cancer assay proved to have a significant impact on treatment decision- making.
      The test reduces chemotherapy use in more than 50% of Korean estrogen receptor
      positive, early breast cancer patients.

PMID- 25381829
TI  - Usefulness of Digital Tomosynthesis for the Detection of Airway Obstruction: A
      Case Report of Bronchial Carcinosarcoma.
AB  - Bronchial carcinosarcoma is a very rare malignant tumor that is composed of
      carcinomatous and sarcomatous elements. We describe the first case in which
      digital tomosynthesis was useful for the evaluation of airway obstruction by
      bronchial carcinosarcoma that was overlooked on initial chest radiography. 

PMID- 25381830
TI  - Phase I dose-escalation study of proton beam therapy for inoperable
      hepatocellular carcinoma.
AB  - PURPOSE: The purpose of this study is to determine the optimal dose of proton
      beam therapy (PBT) in hepatocellular carcinoma (HCC) patients. MATERIALS AND
      METHODS: Inoperable HCC patients who had naive, recurrent, or residual tumor to
      treatment were considered eligible for PBT. Patients received PBT with 60 GyE in
      20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10);
      66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24
      fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined
      by grade >= 3 acute toxicity. RESULTS: Twenty-seven patients were enrolled;
      eight, seven, and 12 patients were treated with dose levels 1, 2, and 3,
      respectively. Overall, treatment was well tolerated, with no dose-limiting
      toxicities. The complete response (CR) rates of primary tumors after PBT for dose
      levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively
      (p=0.039). The 3-and 5-year local progression-free survival (LPFS) rates among 26
      patients, excluding one patient who underwent liver transplantation after PBT due
      to its probable significant effect on disease control, were 79.9% and 63.9%,
      respectively, and the 3-and 5-year overall survival rates were 56.4% and 42.3%,
      respectively. The 3-year LPFS rate was significantly higher in patients who
      achieved CR than in those who did not (90% vs. 40%, p=0.003). CONCLUSION: PBT is
      safe and effective and an EQD2 >= 78 GyE10 should be delivered for achievement of
      local tumor control.

PMID- 25381832
TI  - Australasian Professional Society on Alcohol and other Drugs Conference 2014, 9
      12 November 2014, Adelaide, South Australia.

PMID- 25381831
TI  - Bilateral Internal Auditory Canal Metastasis of Non-small Cell Lung Cancer.
AB  - We report on a patient with brain metastasis involving bilateral internal
      auditory canal from non-small cell lung cancer (NSCLC). A 49-year-old woman who
      had been diagnosed with NSCLC (T2aN1M0) complained of persistent vertigo and
      bilateral tinnitus for three months. The patient had refused all treatments,
      including surgery and chemotherapy; however, she sought alternative medicine. The
      patient's hearing loss showed rapid progression bilaterally, and rotatory vertigo
      with peripheral-type nystagmus developed. Magnetic resonance imaging of the brain
      showed irregular nodular enhancement within both internal auditory canals with
      leptomeningeal enhancement and multiple intracranial metastasis. The patient was
      treated with epidermal growth factor receptor-tyrosine kinase inhibitor, and the
      tumor showed partial response. This was a rare case of multiple brain metastases
      involving bilateral internal auditory canal from known NSCLC presenting with
      vertigo and hearing loss. 

PMID- 25381833
TI  - Innovative models for the empowerment of patients with type 2 diabetes: the
      CAIPaDi program.
AB  - Empowerment interventions for chronic diseases are an evolving process. No
      agreement exists regarding the necessary components and methodologies to be
      applied. Systematic reviews have assessed the effect of self-management
      interventions. Improvements in illness beliefs, adherence to drug therapy and
      glucose monitoring have been reported. In the long term, no major changes have
      been achieved in weight, physical activity, smoking status, and depression
      scores. There is a need for additional studies. The CAIPaDi (Centro de Atencion
      Integral del Paciente con Diabetes) program is an intervention designed to
      provide education and empowerment techniques (using simple low-cost interactive
      tools) over a short period of time followed by at-distance support using internet
      or cell phone technology. The target population consists of patients with type 2
      diabetes, free of chronic complications who are non-smokers. The intervention is
      composed of four monthly visits followed by a continuous at-distance support
      system. At each visit, patients stay for six hours in the center. Information is
      presented in group sessions. Empowerment techniques are applied during individual
      exchanges with the team or during facilitated group sessions. In summary,
      empowerment programs are an unmet need in many healthcare services. This review
      also discusses relevant studies and patents in the management of type 2 diabetes.

PMID- 25381834
TI  - Early initiation of endochondral ossification of mouse femur cultured in hydrogel
      with different mechanical stiffness.
AB  - Mineralization is one of the most important processes in normal bone tissue
      development and in disease condition. Developing a novel and standardized in
      vitro model system that can readily monitor both cellular dynamics and
      mineralization is crucial for better understanding the bone tissue development
      and growth. Recent studies indicated that the mechanical environment is a
      critical condition in mineralization. We hypothesized that hydrogel with
      different mechanical stiffness can provide a biomimetic mechanical environment
      that can modulate bone tissue growth and mineralization. A femur of mouse embryo
      (embryonic day 16) was embedded in agarose hydrogel (2-60 kPa) and cultured in an
      osteogenic medium for a week. Microcomputed tomography (MUCT) results revealed
      enhanced mineralization was detected in the femur head cultured in the gel
      condition, whereas no mineralization in the femur head cultured in the control
      (floating culture) condition. The mineralized region was corresponding to the
      region of secondary ossification center. Both histological and quantitative
      analyses indicated that the mineralized region of femur head cultured in 10 kPa
      gel condition was the highest and the mineralized area was significantly larger
      than that cultured in 2, 40, and 60 kPa gel condition. Immunofluorescence results
      indicated the enhanced mineralization caused by the higher chondrogenic
      differentiation at that region. This enhancement mainly relating to the
      mechanical forces and not to the oxygen tension was also confirmed. Since this
      system enhances and shortens the mineralization procedure compared with the
      conventional two-dimensional or three-dimensional cell culture system, this
      hydrogel system would be one of the unique models for better understanding the
      mineralized tissue development. 

PMID- 25381835
TI  - Predictive impact of daily physical activity on new vascular events in patients
      with mild ischemic stroke.
AB  - BACKGROUND: Daily physical inactivity is associated with a substantially
      increased risk of cardiovascular events. However, the target level of daily
      physical activity remains unclear. AIM: We aimed to evaluate the impact of
      physical activity on long-term vascular events in patients with mild ischemic
      stroke. METHODS: We designed a single hospital-based prospective observational
      study and studied 166 ischemic stroke patients (mean age: 63.9 +/- 9.2) who had a
      modified Rankin Scale 0-1. We measured the daily step count as a variable of the
      daily physical activity after three-months from the stroke onset. Other clinical
      characteristics including age, body mass index, blood pressure, blood laboratory
      tests, vascular function and medications were also assessed. The primary outcomes
      were hospitalization due to stroke recurrence, myocardial infarction, angina
      pectoris and peripheral artery disease. Survival curves were calculated by a
      Kaplan-Meier survival analysis, and the hazard ratios for recurrences were
      determined by univariate and multivariate Cox proportional hazards regression
      models. RESULTS: After a median follow-up periods of 1332 days, 34 vascular
      events (23 stroke recurrences, 11 coronary artery disease) and 7 drop-outs
      occurred, and the remaining patients were divided into two groups: the without
      recurrence group (n = 125) and the with recurrence group (n = 34). The daily step
      count was lower in the nonsurvivor group than in the survivor group. Univariate
      and multivariate Cox proportional hazards analyses revealed that the daily step
      counts was independent predictors of new vascular events. A daily step count
      cutoff value of 6025 steps per day was determined by analyzing the receiver
      operating characteristics that showed a sensitivity of 69.4% and a specificity of
      79.4%. The Kaplan-Meier survival curves after a log-rank test showed a
      significantly lower event rate in the more than 6025 steps per day group compared
      with the less than 6025 steps per day group (P = 0.0002). The positive and
      negative predictive values of less than 6025 steps were 38.0% and 91.6%,
      respectively. CONCLUSION: Our data indicate that daily physical activity
      evaluated by step counts may be useful for forecasting the prognosis in patients
      with mild ischemic stroke. Daily step counts of approximately 6000 steps per day
      may be an initial target level for reducing new vascular events.

PMID- 25381836
TI  - Quality of antiretroviral and opportunistic infection medications dispensed from
      developing countries and Internet pharmacies.
AB  - WHAT IS KNOWN AND OBJECTIVE: Generic manufacturers help decrease the cost of
      antiretroviral (ARV) and antimicrobial medications which are used to treat
      opportunistic infections (OIs) in developing countries. Concerns have been
      expressed about potential quality issues with such medications as a result of the
      identification of numerous counterfeit medications in developing countries.
      However, few studies have assessed the quality of these medications using the
      United States Pharmacopeia (USP) compendial standards. The goal of this study was
      to assess the quality of ARV and OI medications obtained from various sources,
      including South Africa, United States, China, Ethiopia, Thailand, Laos, Mexico,
      Nigeria and five Internet pharmacies. METHODS: Zidovudine, lamivudine, efavirenz,
      nevirapine, isoniazid and sulfamethoxazole/trimethoprim tablets/capsules were
      obtained from eight countries and five Internet pharmacies. The tablets/capsules
      were separated into distinct samples, based on the drug's active ingredient,
      manufacturer and drug control number. Each distinct sample was analysed for drug
      content, dissolution, content uniformity and breaking force using USP 32-National
      Formulary 27 (USP 32-NF 27) compendial methods and compared to the USP standards.
      RESULTS AND DISCUSSION: A total of 2027 tablets/capsules were obtained with 88
      distinct samples identified. All samples met the USP 32-NF 27 standards for drug
      content with a range of 92.7-108.6%. Six of the 88 samples failed the dissolution
      test by 1.5-8.3% below the standard range. Ninety-eight per cent of all 88
      samples met the USP criteria for content uniformity based on weight variation.
      One sample of isoniazid was found to have a low breaking force of 2.8 kiloponds.
      The results of this study show that there were no problems with the samples of
      ARV and OI medications tested for drug quality from the specified locations. As
      there are many studies and reports that discuss the poor quality of generic
      medications with only a few assessing drug quality, the implications of this
      study's results are to: (i) help better understand patient outcomes; (ii) help
      patients gain access to beneficial medications for HIV and OIs; and (iii) ensure
      an overall increase in access to medications where needed. WHAT IS NEW AND
      CONCLUSION: This study is one of the largest to date concerning medication type
      and sample size for the assessment of ARV and OI medications using drug content
      as a measure of quality. The samples were obtained from more diverse geographical
      locations compared to previous studies and, for the first time, included Internet
      pharmacies. In addition to drug content, this study evaluated a more complete
      quality profile including dissolution, content uniformity and breaking force.
      This study showed that drug quality should be assessed consistently in order to
      better identify counterfeit medications compared to current assessments and that
      there should be uniform guidelines for how to assess quality.

PMID- 25381837
TI  - Negative and positive interactions among plants: effects of competitors and
      litter on seedling emergence and growth of forest and grassland species.
AB  - Living plant neighbours, but also their dead aboveground remains (i.e. litter),
      may individually exert negative or positive effects on plant recruitment.
      Although living plants and litter co-occur in most ecosystems, few studies have
      addressed their combined effects, and conclusions are ambivalent. Therefore, we
      examined the response in terms of seedling emergence and growth of herbaceous
      grassland and forest species to different litter types and amounts and the
      presence of competitors. We conducted a pot experiment testing the effects of
      litter type (grass, oak), litter amount (low, medium, high) and interspecific
      competition (presence or absence of four Festuca arundinacea individuals) on
      seedling emergence and biomass of four congeneric pairs of hemicryptophytes from
      two habitat types (woodland, grassland). Interactions between litter and
      competition were weak. Litter presence increased competitor biomass. It also had
      positive effects on seedling emergence at low litter amounts and negative effects
      at high litter amounts, while competition had no effect on seedling emergence.
      Seedling biomass was negatively affected by the presence of competitors, and this
      effect was stronger in combination with high amounts of litter. Litter affected
      seedling emergence while competition determined the biomass of the emerged
      individuals, both affecting early stages of seedling recruitment. High litter
      accumulation also reduced seedling biomass, but this effect seemed to be additive
      to competitor effects. This suggests that live and dead plant mass can affect
      species recruitment in natural systems, but the mechanisms by which they operate
      and their timing differ. 

PMID- 25381838
TI  - Response to Cragun et al.

PMID- 25381839
TI  - Review: efficacy and safety of hybrid therapy for Helicobacter pylori infection:
      a systematic review and meta-analysis.
AB  - OBJECTIVES: To assess the efficacy and safety of hybrid therapy compared to other
      pre-existing therapies and to new therapies. METHODS: Through a search of PubMed,
      EMBASE, the Cochrane Central Register of Controlled Trials, and Conference
      Proceedings Citation Index, two independent reviewers systemically identified
      randomized, controlled trials that compared hybrid therapy to other pre-existing
      and new therapies. Dichotomous data were pooled to obtain the relative risk (RR)
      of the eradication rate, with 95% confidence intervals (CIs). RESULTS: We
      identified 6 studies, 5 of which compared hybrid therapy and sequential therapy,
      and 3 of which compared hybrid therapy and concomitant therapy. Pooled estimates
      of the 5 randomized controlled trials (RCTs) revealed no significant differences
      between hybrid therapy and sequential therapy and no evidence of heterogeneity
      (I(2)  = 0%; p = .803), the pooled RRs were 1.02 (95% CI: 0.93-1.12) (intention
      to-treat (ITT)), and 1.03 (95% CI: 0.94-1.13) (per protocol (PP)). Pooled
      estimates of the 3 RCTs showed no significant differences between hybrid therapy
      and concomitant therapy with no evidence of heterogeneity (I(2)  = 0%; p = .967),
      the pooled RRs were 0.99 (95% CI: 0.89-1.10) (ITT) and 0.99 (95% CI: 0.89-1.10)
      (PP). No significant differences in adverse events were noted among hybrid
      therapy, sequential therapy, and concomitant therapy ((RR: 1.13; 95% CI: 0.87
      1.48; I(2)  = 13.2%; p = .327), (RR: 0.89; 95% CI: 0.73-1.08; I(2)  = 0%; p =
      .978) (ITT), respectively). After consideration of all treatment arms, the ITT
      eradication rates with hybrid therapy, concomitant therapy, and sequential
      therapy were 88.6, 86.3, and 84.7%, respectively. And the PP eradication rates
      were 92.1, 92.5, and 87.5%. No significant differences were observed between the
      groups in terms of compliance. CONCLUSIONS: All three of these therapies yielded
      good eradication rates. Hybrid therapy could be an alternative to sequential
      therapy and concomitant therapy, but additional RCTs are needed to confirm this
      finding.

PMID- 25381840
TI  - Sensitivity of proposed clinical decision rules for subarachnoid haemorrhage: An
      external validation study.
AB  - OBJECTIVES: Subarachnoid haemorrhage (SAH) is an uncommon but important cause of
      sudden-onset headache. Three clinical decision rules (CDRs) for investigation in
      sudden headache have been proposed, but concerns were raised about the
      generalisability of some variables. Our aim was to determine what proportion of
      patients with confirmed SAH has the identified high-risk factors and the
      sensitivity of the proposed CDR in an Australasian cohort. METHODS: This is a
      retrospective cohort study of alert and neurologically intact adult patients with
      confirmed SAH attending two community teaching hospitals between 2000 and 2011.
      The outcomes of interest were the proportion of patients with each high-risk
      criterion (descriptive statistics) and sensitivity of each proposed CDR (%,
      interquartile range [IQR]). RESULTS: There were 59 confirmed SAH that met the
      inclusion criteria. Sensitivity of proposed CDR 1 was 96.6% (95% confidence
      interval [CI] 88.5-99.1%), sensitivity of proposed CDR 2 was 100% (95% CI 93.9
      100%) and sensitivity of proposed CDR 3 was 89.8% (95% CI 79.5-95.3%). The
      addition of vomiting to the criteria in CDRs 1 and 3 increased the sensitivity of
      both these CDRs to 100%. CONCLUSION: CDR 2, or the refinement of CDRs 1 and 3
      with the inclusion of at least one episode of vomiting as a criterion, has very
      high sensitivity. Although unlikely to reduce CT scan rates for patients in whom
      there is a clinical suspicion of SAH, they might be useful in guiding which
      patients require further testing (e.g. lumbar puncture) after a negative CT scan.

PMID- 25381841
TI  - Repeated administration of IL-31 upregulates IL-31 receptor A (IL-31RA) in dorsal
      root ganglia and causes severe itch-associated scratching behaviour in mice.
AB  - We investigated the effects of repeated administration of interleukin-31 (IL-31)
      on itch-associated scratching counts (long-lasting scratching, LLS) and IL-31
      related receptor mRNA expression in mice. Intra-dermal (i.d.) injection of IL-31
      (100 and 300 ng/site) every 12 h for 3 days significantly increased LLS. Repeated
      administration of IL-31 also increased the expression of IL-31 receptor A (IL
      31RA) and oncostatin M receptor beta (OSMRbeta) in dorsal root ganglia (DRG).
      After the repeated administration of IL-31 was discontinued, IL-31RA expression
      decreased and reached the baseline level 2 days after the last dose of IL-31. LLS
      changed along with DRG IL-31RA expression. Moreover, IL-31-induced IL-31RA
      protein expression was confirmed by Western blotting analysis. These data suggest
      that IL-31 upregulates IL-31RA expression in DRG neuron cell bodies, and
      cutaneous-injected IL-31-induced itching is enhanced by DRG IL-31RA expression in
      mice. 

PMID- 25381842
TI  - The natural history of occult or angiodysplastic gastrointestinal bleeding in von
      Willebrand disease.
AB  - Recurrent gastrointestinal bleeding is one of the most challenging complications
      encountered in the management of patients with von Willebrand disease (VWD). The
      commonest cause is angiodysplasia, but often no cause is identified due to the
      difficulty in making the diagnosis. The optimal treatment to prevent recurrences
      remains unknown. We performed a retrospective study of VWD patients with occult
      or angiodysplastic bleeding within the setting of the von Willebrand Disease
      Prophylaxis Network (VWD PN) to describe diagnostic and treatment strategies.
      Centres participating in the VWD PN recruited subjects under their care with a
      history of congenital VWD and gastrointestinal (GI) bleeding due to
      angiodysplasia, or cases in which the cause was not identified despite
      investigation. Patients with acquired von Willebrand syndrome or those for whom
      the GI bleeding was due to another cause were excluded. Forty-eight patients from
      18 centres in 10 countries were recruited. Seven individuals had a family history
      of GI bleeding and all VWD types except 2N were represented. Angiodysplasia was
      confirmed in 38%, with video capsule endoscopy and GI tract endoscopies being the
      most common methods of making the diagnosis. Recurrent GI bleeding in VWD is
      associated with significant morbidity and required hospital admission on up to 30
      occasions. Patients were treated with multiple pharmacological agents with
      prophylactic von Willebrand factor concentrate being the most efficient in
      preventing recurrence of the GI bleeding. The diagnosis and treatment of
      recurrent GI bleeding in congenital VWD remains challenging and is associated
      with significant morbidity. Prophylactic treatment with von Willebrand factor
      concentrate was the most effective method of preventing recurrent bleeding but
      its efficacy remains to be confirmed in a prospective study. 

PMID- 25381843
TI  - Medico-legal evaluation of firearm injuries--an original study from India with
      review of literature.
AB  - Firearm (FA) injuries pose great health burden and presents enormous challenge
      for health and national economies. This study was undertaken to analyze the
      characteristics of fatal gunshot injuries, their pattern, associated factors, and
      postmortem findings in central India, to provide data for such fatalities in this
      region, which has not been reported earlier. This is a descriptive, retrospective
      cross-sectional study carried out on the victims of FA injuries referred to the
      mortuary. Of the autopsies conducted during study, 2.09% were firearm-related
      deaths. Of the cases, males (92.42%) notably outnumbered females in a ratio of
      12.2:1. Homicidal attacks were maximum, and unlicensed, illegal country-made
      weapons were the preferred choice. Suicides were least. Result signifies that
      illegal country-made weapons should be strictly limited to save the precious
      lives. A holistic approach encompassing public awareness, behavioral
      modification, and stringent management of law and order is the need of the hour. 

PMID- 25381845
TI  - Broadband focusing and collimation of water waves by zero refractive index.
AB  - It is always a challenge to realize extreme and unusual values of refractive
      index for a broad range of frequencies. We show that when water is covered by a
      thick, rigid and unmovable plate, it behaves like a medium with zero refractive
      index for water waves at any frequency. Hence, by covering water with a plate of
      a concave or rectangular shape, water waves can be focused or collimated in a
      broad range of frequencies. Experiments were conducted to demonstrate these
      effects and results are in excellent agreement with numerical simulations. 

PMID- 25381846
TI  - Just another day?

PMID- 25381844
TI  - Prediction of cancer-specific survival after radical cystectomy in pT4a
      urothelial carcinoma of the bladder: development of a tool for clinical decision
      making.
AB  - OBJECTIVE: To externally validate the pT4a-specific risk model for cancer
      specific survival (CSS) proposed by May et al. (Urol Oncol 2013; 31: 1141-1147)
      and to develop a new pT4a-specific nomogram predicting CSS in an international
      multicentre cohort of patients undergoing radical cystectomy (RC) for urothelial
      carcinoma of the bladder (UCB) PATIENTS AND METHODS: Data from 856 patients with
      pT4a UCB treated with RC at 21 centres in Europe and North-America were assessed.
      The risk model proposed by May et al., which includes female gender, presence of
      positive lymphovascular invasion (LVI) and lack of adjuvant chemotherapy
      administration as adverse predictors for CSS, was applied to our cohort. For the
      purpose of external validation, model discrimination was measured using the
      receiver-operating characteristic-derived area under the curve. A nomogram for
      predicting CSS in pT4a UCB after RC was developed after internal validation based
      on multivariable Cox proportional hazards regression analysis evaluating the
      impact of clinicopathological variables on CSS. Decision-curve analyses were
      applied to determine the net benefit derived from the two models. RESULTS: The
      estimated 5-year-CSS after RC was 34% in our cohort. The risk model devised by
      May et al. predicted individual 5-year-CSS with an accuracy of 60.1%. In
      multivariable Cox proportional hazards regression analysis, female gender (hazard
      ratio [HR] 1.45), LVI (HR 1.37), lymph node metastases (HR 2.54), positive soft
      tissue surgical margins (HR 1.39), neoadjuvant (HR 2.24) and lack of adjuvant
      chemotherapy (HR 1.67, all P < 0.05) were independent predictors of an adverse
      CSS rate and formed the features of our nomogram with a predictive accuracy of
      67.1%. Decision-curve analyses showed higher net benefits for the use of the
      newly developed nomogram in our cohort over all thresholds. CONCLUSIONS: The risk
      model devised by May et al. was validated with moderate discrimination and was
      outperformed by our newly developed pT4a-specific nomogram in the present study
      population. Our nomogram might be particularly suitable for postoperative patient
      counselling in the heterogeneous cohort of patients with pT4a UCB.

PMID- 25381847
TI  - Meeting the complex needs of individuals living with HIV: a case study approach.
AB  - This article critically discusses the nursing care and management of a person
      living with the human immunodeficiency virus (HIV) infection as a long-term
      condition, requiring highly complex HIV care. Complex HIV care is managed in the
      secondary care setting. However, recent legislation has motivated shifts in HIV
      care to the community care setting. This article aims to enhance health
      professionals' understanding in order to equip practice and district nurses to
      deliver HIV care provision. Antiretroviral adherence is a prerequisite for
      disease survival as well as an essential component of complete HIV self-care
      management. It is therefore imperative that nurses tailor adherence strategies
      according to each patient's requirements. Case management strategies such as the
      use of cognitive behavioural therapy to alleviate depressive symptoms will be
      considered. Furthermore, the use of motivational interviewing for antiretroviral
      adherence is highlighted as a potential intervention to help patients overcome
      the physical, psychological and physiological challenges of living with HIV
      associated comorbidities. The delivery of integrated HIV care is pivotal for the
      management of the person living with HIV, as is the facilitation of a self-caring
      behaviour. 

PMID- 25381848
TI  - Community-dwelling women's knowledge of urinary incontinence.
AB  - As the population ages, the risk and prevalence of urinary incontinence (UI) will
      increase. Although this is the case, many women do not seek help or treatment. It
      is therefore important to investigate women's knowledge of UI. This pilot study
      aimed to describe community-dwelling women's knowledge of UI. A convenience
      sample method was used to recruit 50 community-dwelling women aged 50 and over.
      Some 36 participants completed a demographic questionnaire and the Urinary
      Incontinence Knowledge Scale (UIKS)-a response rate of 72%. The findings
      indicated that participants had poor knowledge of UI, principally in relation to
      risk, prevention, treatment and management factors. Fewer than 20% of
      participants indicated they had been given information on bladder and bowel
      health issues. The findings suggested that women had unmet educational needs
      relating to UI. Community nurses have a key role to play in promoting targeted
      awareness and continence education advice regarding UI to community-dwelling
      women. 

PMID- 25381849
TI  - The importance of effective catheter securement.
AB  - With the number of catheter users increasing in an ageing population with
      increased comorbidities, Drew Payne argues that understanding catheter securement
      is paramount to good care. 

PMID- 25381850
TI  - Anticipatory prescribing at the end of life in Lothian care homes.
AB  - Common symptoms at the end of life include pain, breathlessness, anxiety,
      respiratory secretions and nausea. National end-of-life care strategies advocate
      anticipatory prescribing for timely management of these symptoms to enhance
      patient care by preventing unnecessary distress. This study investigated the
      extent to which residents in eight Lothian care homes had anticipatory
      medications prescribed prior to death. Data were collected as part of a service
      development project to improve palliative care in nursing care homes in
      Edinburgh. Of the 77 residents who died in the care homes, 54% had anticipatory
      medicines prescribed. Only 15% had prescriptions for all four nationally
      recommended anticipatory medications. Many care home residents do not have the
      recommended anticipatory medications in place in the last days of life and thus
      may experience inadequate symptom control. Interventions that increase the
      availability of anticipatory medicines to manage common symptoms at the end of
      life for care home residents are required. 

PMID- 25381851
TI  - The use of patient management systems in the community.
AB  - The role of community nursing services is changing and the ability to adapt to
      the new roles and challenges using technology is becoming increasingly important.
      This article considers the positive role that using patient management systems
      and care registers can play in improving and developing new work patterns through
      the use of online, shared working practices.- 

PMID- 25381853
TI  - Older carers in the UK: who cares?
AB  - Long-term care in the UK relies heavily on informal and unpaid carers.
      Statistical data regarding the number of carers in the 2001 Census compared with
      the 2011 Census identify an increase of around 600 000 carers. It is also
      significant that many of these carers are themselves in their late middle age.
      The reasons for taking on the caring role are varied, but there are significant
      potential physical, mental and financial issues associated with taking on the
      caring role. Positive benefits in terms of support provision for the carer do
      exist, but support services across the UK are variable. This article outlines the
      problems that may be faced by carers and provides directions for future
      developments and research into how this situation might be improved. 

PMID- 25381852
TI  - The role and organisation of community palliative specialist nursing teams in
      rural England.
AB  - This article describes a study that used a qualitative approach, purposive
      sampling and semi-structured telephone interviews conducted with specialist
      palliative care nurses from six rural community teams in England. The study
      investigated how services were organised and the issues of delivering specialist
      palliative nursing care in a rural area. Qualitative content analysis was used to
      analyse the data. The findings showed many similarities in that the majority of
      patients in rural areas were not accessing hospice services and there was a
      greater reliance on care at home. However, the challenges in delivering care
      ranged from managing patient expectations, geographical distance, lack of
      technology to support remote working and education for the specialist palliative
      care teams. The study makes specific recommendations for rural community
      specialist palliative care teams. 

PMID- 25381854
TI  - Change management in diabetes care.

PMID- 25381855
TI  - Men and the challenge of prostate cancer.

PMID- 25381856
TI  - Interpreting guidance on prosecution for assisted dying for district nurses.
AB  - Following a ruling by the House of Lords in 2009, the Director of Public
      Prosecutions issued guidance setting out the circumstances that would be likely
      to lead to the prosecution of a person for encouraging or assisting suicide under
      the Suicide Act 1961, section 2. In that guidance, a district nurse assisting a
      person to commit suicide would be one of the circumstances that would lead to
      prosecution. The Director of Public Prosecutions recently unexpectedly amended
      her guidance in relation to health professionals. This article discusses the
      implications of the amendment and argues that it will cause confusion among
      district nurses and give rise to an unrealistic expectation about the role a
      district nurse can lawfully take in assisting a person to die. 

PMID- 25381857
TI  - Where is the recognition of community nurses?

PMID- 25381858
TI  - Lipopolysaccharide amplifies eosinophilic inflammation after segmental challenge
      with house dust mite in asthmatics.
AB  - BACKGROUND: House dust contains mite allergens as well as bacterial products such
      as lipopolysaccharide (LPS). Asthma exacerbations are associated with the level
      of exposure to allergens and LPS. LPS can potentiate allergen effects in steroid
      naive patients. Long-acting beta2-agonists (LABA) were shown to inhibit LPS
      induced bronchial inflammation in healthy volunteers. The aim of this study was
      to assess the effect of LPS on the allergen-induced eosinophilic inflammation
      [primary endpoints: eosinophil counts and eosinophil cationic protein (ECP)]
      induced by bronchial instillation of house dust mite (HDM) in patients with
      asthma on maintenance treatment with inhaled corticosteroids (ICS). METHODS:
      Thirty-two nonsmoking asthmatics with HDM allergy were treated with run-in
      medication (fluticasone propionate 100 MUg bid) during 2 weeks before the study
      day. All patients underwent bronchial challenge with HDM, and half of them were
      randomized to receive additional LPS. Both groups were randomized to receive
      pretreatment with a single inhalation of 100 MUg salmeterol 30 min before
      bronchial segmental challenge. Six hours later, bronchoalveolar lavage (BAL) was
      collected for leukocyte cell count, differentials, and cellular activation
      markers. RESULTS: Challenge with HDM/LPS induced a significant increase in
      eosinophil cationic protein (P = 0.036) and a trend toward an increase in BALF
      eosinophils as compared to HDM challenge. CONCLUSION: Lipopolysaccharide promotes
      eosinophilic airway inflammation in patients with asthma despite being on
      maintenance treatment with ICS.

PMID- 25381860
TI  - Walk the talk: how to efficiently present medical histories.

PMID- 25381861
TI  - Human papillomavirus vaccination.

PMID- 25381859
TI  - Sporadic late-onset nemaline myopathy as a rare cause of slowly progressive
      muscle weakness with young adult onset.
AB  - INTRODUCTION: Sporadic late-onset nemaline myopathy (SLONM) is a rare intractable
      acquired myopathy characterized by progressive muscle weakness and atrophy,
      usually with middle to late adult onset. Autologous peripheral blood stem cell
      transplantation (auto-PBSCT) has been reported to be a promising treatment for
      SLONM. METHODS: In this study we performed clinical characterization, muscle
      histopathological analysis, and muscle power monitoring after auto-PBSCT in a 27
      year-old HIV-negative man with monoclonal gammopathy. RESULTS: He showed improved
      muscle strength after treatment with high-dose melphalan and auto-PBSCT.
      CONCLUSIONS: Considering the recent reports of successful treatment of SLONM,
      early and correct diagnosis of this condition in association with monoclonal
      gammopathy is important. SLONM should be added to the list of diseases to
      consider in the differential diagnosis of progressive muscle weakness with young
      adult onset.

PMID- 25381862
TI  - Examination of the cervix.

PMID- 25381863
TI  - IgA nephropathy.

PMID- 25381864
TI  - Quantitative Measurements of HO2 and other products of n-butane oxidation (H2O2,
      H2O, CH2O, and C2H4) at elevated temperatures by direct coupling of a jet-stirred
      reactor with sampling nozzle and cavity ring-down spectroscopy (cw-CRDS).
AB  - For the first time quantitative measurements of the hydroperoxyl radical (HO2) in
      a jet-stirred reactor were performed thanks to a new experimental setup involving
      fast sampling and near-infrared cavity ring-down spectroscopy at low pressure.
      The experiments were performed at atmospheric pressure and over a range of
      temperatures (550-900 K) with n-butane, the simplest hydrocarbon fuel exhibiting
      cool flame oxidation chemistry which represents a key process for the auto
      ignition in internal combustion engines. The same technique was also used to
      measure H2O2, H2O, CH2O, and C2H4 under the same conditions. This new setup
      brings new scientific horizons for characterizing complex reactive systems at
      elevated temperatures. Measuring HO2 formation from hydrocarbon oxidation is
      extremely important in determining the propensity of a fuel to follow chain
      termination pathways from R + O2 compared to chain branching (leading to OH),
      helping to constrain and better validate detailed chemical kinetics models. 

PMID- 25381865
TI  - A homodimeric BODIPY rotor as a fluorescent viscosity sensor for membrane
      mimicking and cellular environments.
AB  - Fluorescence properties of a novel homodimeric BODIPY dye rotor for Fluorescence
      Lifetime Imaging Microscopy (FLIM) are reported. Steady state and time resolved
      fluorescence measurements established the viscosity dependent behaviour in vitro.
      Homodimeric BODIPY embedded in different membrane mimicking lipid vesicles (DPPC,
      POPC and POPC plus cholesterol) is demonstrated to be a viable sensor for
      fluorescence lifetime based viscosity measurements. Moreover, SKOV3 cells readily
      endocytosed the dye, which accumulated in membranous structures inside the
      cytoplasm thereby allowing viscosity mapping of internal cell components. 

PMID- 25381866
TI  - Quantifying biased response of axon to chemical gradient steepness in a
      microfluidic device.
AB  - Axons are very sensitive to molecular gradients and can discriminate extremely
      small differences in gradient steepness. Microfluidic devices capable of
      generating chemical gradients and adjusting their steepness could be used to
      quantify the sensitivity of axonal response. Here, we present a versatile and
      robust microfluidic device that can generate substrate-bound molecular gradients
      with evenly varying steepness on a single chip to precisely quantify axonal
      response. In this device, two solutions are perfused into a central channel via
      two inlets while partially flowing into two peripheral channels through
      interconnecting grooves, which gradually decrease the fluid velocity along the
      central channel. Molecular gradients with evenly and gradually decreased
      steepness can therefore be generated with a high resolution that is less than
      0.05%/mm. In addition, the overall distribution range and resolution of the
      gradient steepness can be highly and flexibly controlled by adjusting various
      parameters of the device. Using this device, we quantified the hippocampal axonal
      response to substrate-bound laminin and ephrin-A5 gradients with varying
      steepnesses. Our results provided more detailed information on how and to what
      extent different steepnesses guide hippocampal neuron development during the
      initial outgrowth. Furthermore, our results show that axons can sensitively
      respond to very shallow laminin and ephrin-A5 gradients, which could effectively
      initiate biased differentiation of hippocampal neurons in the steepness range
      investigated in this study. 

PMID- 25381867
TI  - Preparation of cycloheptane ring by nucleophilic cyclopropanation of 1,2
      diketones with bis(iodozincio)methane.
AB  - The nucleophilic cyclopropanation of hexa-1,5-diene-3,4-diones with
      bis(iodozincio)methane afforded the Zn alkoxides of cis-dialkenylcyclopropane-1,2
      diols stereoselectively. The subsequent oxy-Cope rearrangement afforded the
      corresponding Zn alkoxides of 5,6-dialkylcyclohepta-3,7-diene-1,3-diols. 

PMID- 25381868
TI  - The grain of spatially referenced economic cost and biodiversity benefit data and
      the effectiveness of a cost targeting strategy.
AB  - Facing tight resource constraints, conservation organizations must allocate funds
      available for habitat protection as effectively as possible. Often, they combine
      spatially referenced economic and biodiversity data to prioritize land for
      protection. We tested how sensitive these prioritizations could be to differences
      in the spatial grain of these data by demonstrating how the conclusion of a
      classic debate in conservation planning between cost and benefit targeting was
      altered based on the available information. As a case study, we determined parcel
      level acquisition costs and biodiversity benefits of land transactions recently
      undertaken by a nonprofit conservation organization that seeks to protect forests
      in the eastern United States. Then, we used hypothetical conservation plans to
      simulate the types of ex ante priorities that an organization could use to
      prioritize areas for protection. We found the apparent effectiveness of cost and
      benefit targeting depended on the spatial grain of the data used when
      prioritizing parcels based on local species richness. However, when accounting
      for complementarity, benefit targeting consistently was more efficient than a
      cost targeting strategy regardless of the spatial grain of the data involved.
      More pertinently for other studies, we found that combining data collected over
      different spatial grains inflated the apparent effectiveness of a cost targeting
      strategy and led to overestimation of the efficiency gain offered by adopting a
      more integrative return-on-investment approach. 

PMID- 25381869
TI  - Effective radiation doses associated with non-invasive versus invasive assessment
      of coronary anatomy and physiology.
AB  - OBJECTIVES: To compare the effective radiation dose (ERD) needed to obtain
      information on coronary anatomy and physiology by a non-invasive versus an
      invasive diagnostic strategy. BACKGROUND: Knowledge of anatomy and physiology is
      needed for management of patients with coronary artery disease (CAD). There is,
      however, a growing concern about detrimental long-term effects of radiation
      associated with diagnostic procedures. METHODS: In a total of 671 patients with
      suspected CAD, we compared the ERD needed to obtain anatomical and physiological
      information through a non-invasive strategy or an invasive strategy. The non
      invasive strategy consisted of coronary computed tomography angiography (CCTA)
      and single photon emission computed tomography (SPECT). The invasive strategy
      included coronary angiography (CA) and fractional flow reserve (FFR) measurement.
      In 464 patients, the data were acquired in Period 2009 and in 207 the data were
      acquired in Period 2011 (after each period, the CCTA- and the CA-equipment had
      been upgraded). RESULTS: For the Period 2009 total ERD of the non-invasive
      approach was significantly larger compared to the invasive approach (28.45 +/-
      5.37 mSv versus 15.79 +/- 7.95 mSv, respectively; P < 0.0001). For Period 2011,
      despite the significant decrease in ERD for both groups (P<0.0001 for both), the
      ERD remained higher for the non-invasive approach compared to the invasive
      approach (16.67 +/- 10.45 mSv vs. 10.36 +/- 5.87 mSv, respectively; P < 0.0001).
      Simulation of various diagnostic scenarios showed cumulative radiation dose is
      the lowest when a first positive test is followed by an invasive strategy.
      CONCLUSION: To obtain anatomic and physiologic information in patients with
      suspected CAD, the combination of CA and FFR is associated with lower ERD than
      the combination of CCTA and SPECT.

PMID- 25381870
TI  - UV-triggered dopamine polymerization: control of polymerization, surface coating,
      and photopatterning.
AB  - UV irradiation is demonstrated to initiate dopamine polymerization and deposition
      on different surfaces under both acidic and basic pH. The observed acceleration
      of the dopamine polymerization is explained by the UV-induced formation of
      reactive oxygen species that trigger dopamine polymerization. The UV-induced
      dopamine polymerization leads to a better control over polydopamine deposition
      and formation of functional polydopamine micropatterns. 

PMID- 25381871
TI  - From Margins to Center: An Oral History of the Wartime Experience of Iranian
      Nurses in Iran-Iraq War, 1980-1988.
AB  - Abstract Background: The extensive nature of the Iraq-Iran war converted to a
      human tragedy with large casualties; it has affected nursing discipline
      dramatically. Aim: To analyze the history of the wartime experience of Iranian
      nurses in Iran-Iraq war. Method: The current study was conducted with oral
      history. The study sample consisted of 13 Iranian nurses who served in the war
      zones during the wartime. Purposive and snowball sampling were used to recruit
      the participants. During the face-to-face interviews, participants were asked to
      describe their experience in the war zones at the war years. Data collection and
      analysis took place from April to August 2013, when saturation was reached. All
      interviews were tape recorded and transcribed and then analyzed with thematic
      content analysis. Results: Finally, 5 themes and 18 subthemes emerged from data
      analysis of significant statements from 17 interviews. The five emerged themes
      included (1) "From margin to center," (2) "Development of referral care," (3)
      "Personal and professional growth and development," (4) "The emerging pillar of
      culture in war nursing," and (5) "Threats to nursing at the war". Conclusion and
      relevance to clinical practice: Nursing in Iran at wartime has a difficult path
      to development. There are powerful implications for clinical practice. It is
      recommended to continue collection, archiving, and analyzing the wartime
      experiences of Iranian nurses.

PMID- 25381873
TI  - Using the ubiquitous pH meter combined with a loop mediated isothermal
      amplification method for facile and sensitive detection of Nosema bombycis
      genomic DNA PTP1.
AB  - Here we show an amplification-coupled detection method for directly measuring
      released hydrogen ions during the loop mediated isothermal amplification (LAMP)
      procedure by using a pH meter. The genomic DNA of Nosema bombycis (N. bombycis)
      was amplified and detected by employing this LAMP-pH meter platform for the first
      time. 

PMID- 25381872
TI  - Implementation of transcranial Doppler ultrasonography screening and primary
      stroke prevention in urban and rural sickle cell disease populations.
AB  - BACKGROUND: Transcranial Doppler (TCD) ultrasonography identifies children with
      sickle cell disease (SCD) at increased risk of stroke. Initiation of chronic
      transfusions as primary stroke prevention in children with abnormal TCD
      significantly reduces stroke risk. Here, we report the results describing the
      implementation of TCD screening and primary stroke prevention in both urban and
      rural clinical practices. PROCEDURE: Retrospective chart review identified
      children ages 2-16 years with Hgb SS or Sbeta0 -thalassemia and no history of
      stroke followed in either the local urban or rural SCD clinics at Georgia Regents
      University. We defined standard of care (SOC) as having one TCD performed
      annually between January 2010 and December 2012 starting at age 2 years. RESULTS:
      A total of 195 patients were included in the evaluation of SOC screening, overall
      41% achieved SOC. There was no difference in SOC between the two clinics (35%
      urban and 47.4% rural). The majority of patients with abnormal TCDs are on
      chronic transfusions (83%), and none have experienced a stroke. Monitoring of
      effects of transfusion was difficult with 38% and 31% of rural patients lacking
      documentation of Hgb S% and ferritin levels, respectively, in the past year.
      CONCLUSIONS: We report here data describing primary stroke prophylaxis in rural
      patients. SOC rates are similar between the two clinical settings. While
      implementation of primary stroke prevention in rural patients was difficult,
      rural TCD screening is feasible and can achieve SOC equal to that in an urban
      setting. This suggests that barriers exist in provided primary stroke prevention
      to all patients. Pediatr Blood Cancer 2015;62:219-223. (c) 2014 Wiley
      Periodicals, Inc.

PMID- 25381874
TI  - Hybrid organic-inorganic colloidal composite 'sponges' via internal crosslinking.
AB  - An effective method for the generation of hybrid organic-inorganic nanocomposite
      microparticles featuring controlled size and high structural stability is
      presented. In this process, an oil-in-water Pickering emulsion is formed using
      hydrophilic amine-functionalized silica nanoparticles. Covalent modification
      using a hydrophobic maleic anhydride copolymer then alters nanoparticle
      wettability during crosslinking, causing a core-shell to nanocomposite structural
      reorganization of the assemblies. The resulting porous nanocomposites maintain
      discrete microparticle structures and retain payloads in their oil phase even
      when incubated in competitive solvents such as ethanol. 

PMID- 25381875
TI  - Reply to The effect of vigorous physical activity and body composition on
      cortical bone mass in adolescence.

PMID- 25381876
TI  - Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes:
      a randomized double-blind placebo-controlled 102-week trial.
AB  - AIMS: To assess initial pharmacotherapy of Type 2 diabetes with the sodium
      glucose cotransporter-2 inhibitor dapagliflozin. METHODS: This double-blind,
      placebo-controlled trial, randomly allocated people with Type 2 diabetes aged 18
      77 years and inadequate glycaemic control on diet and exercise [HbA1c 53-86
      mmol/mol (7.0-10.0%)] to receive placebo (n = 75) or dapagliflozin monotherapy
      2.5 mg (n = 65), 5 mg (n = 64) or 10 mg (n = 70) once daily in the morning. After
      24 weeks, low-dose double-blind metformin 500 mg/day was added to the placebo
      group regimen (placebo+low-dose metformin group). Changes in HbA1c level, fasting
      plasma glucose and body weight, as well as adverse events, were assessed over 102
      weeks. RESULTS: Of the 274 participants randomized, 167 completed the study
      (60.9%). At 102 weeks, significant differences vs placebo+low-dose metformin with
      dapagliflozin 5 and 10 mg were observed for HbA1c (-5.8 mmol/mol [-0.53%], P =
      0.018; and -4.8 mmol/mol [-0.44%], P = 0.048), respectively); and for FPG (-0.69
      mmol/L, P = 0.044; and -1.12 mmol/l, P = 0.001, respectively). For body weight,
      the difference between the dapagliflozin 10-mg group and the placebo+low-dose
      metformin group was significant (-2.60 kg; P = 0.016). Hypoglycaemic events were
      uncommon, with rates of 5.3% for placebo+low-dose metformin group and 0-4.6% for
      the dapagliflozin groups. Genital infections and urinary tract infections were
      more common in the dapagliflozin groups than in the placebo+low-dose metformin
      group. CONCLUSIONS: Dapagliflozin as monotherapy in treatment-naive people with
      early Type 2 diabetes improved glycaemic control and reduced weight without
      increasing hypoglycaemia over 102 weeks. Dapagliflozin may provide an alternative
      initial pharmacotherapy in such people.

PMID- 25381877
TI  - Site-specific conjugation of an antibody-binding protein catalyzed by horseradish
      peroxidase creates a multivalent protein conjugate with high affinity to IgG.
AB  - Cross-linking proteins offers an approach to enhance the distinct function of
      proteins due to the multivalent effect. In this study, we demonstrated the
      preparation of a multivalent antibody-binding protein possessing high affinity to
      IgG by conjugating a number of antibody-binding proteins using the horseradish
      peroxidase (HRP)-mediated protein conjugation method. By introducing a peptide
      tag containing a tyrosine (Y-tag) to the C-terminus of the model protein, a
      chimera protein of protein G and protein A (pG2 pA), the Tyr residue in the Y-tag
      was efficiently recognized by HRP and cross-linked with each other to yield a pG2
      pA conjugate, composed of mainly two to three units of pG2 pA. The cross-linking
      occurred site specifically at the Tyr residue in the Y-tag and introduction of
      the Y-tag showed no effect on the function of pG2 pA. The affinity of the Y
      tagged pG2 pA conjugate against IgG clearly increased because of the multivalent
      effect, demonstrating the benefit of this protein cross-linking reaction, which
      yields functional protein oligomers. Such multivalent protein conjugates created
      by this reaction should have potential to be used in ELISA and Western blotting
      applications in which highly sensitive detection of target molecules is desired. 

PMID- 25381878
TI  - Preparation and characterization of novel carbon dioxide adsorbents based on
      polyethylenimine-modified Halloysite nanotubes.
AB  - New nano-sized carbon dioxide (CO2) adsorbents based on Halloysite nanotubes
      impregnated with polyethylenimine (PEI) were designed and synthesized, which were
      excellent adsorbents for the capture of CO2 at room temperature and had
      relatively high CO2 adsorption capacity. The prepared adsorbents were
      characterized by various techniques such as Fourier transform infrared
      spectrometry, gel permeation chromatography, dynamic light scattering,
      thermogravimetry, thermogravimetry-Fourier transform-infrared spectrometry,
      scanning electron microscopy and transmission electron microscopy. The adsorption
      characteristics and capacity were studied at room temperature, the highest CO2
      adsorption capacity of 156.6 mg/g-PEI was obtained and the optimal adsorption
      capacity can reach a maximum value of 54.8 mg/g-adsorbent. The experiment
      indicated that this kind of adsorbent has a high stability at 80 degrees C and
      PEI-impregnated adsorbents showed good reversibility and stability during cyclic
      adsorption-regeneration tests. 

PMID- 25381881
TI  - Pathogen variation across time and space: sequencing to characterize Mannheimia
      haemolytica diversity.
AB  - Bovine respiratory disease complex (BRDC) is a major animal health and economic
      issue that affects cattle industries worldwide. Within the USA, the beef cattle
      industry loses up to an estimated 1 billion dollars a year due to BRDC. There are
      many contributors to BRDC, including environmental stressors and viral and/or
      bacterial infections. One species of bacteria in particular, Mannheimia
      haemolytica, is recognized as the major cause of severe fibrinonecrotic pneumonia
      in cattle. M. haemolytica is an opportunistic pathogen that normally populates
      the upper respiratory tract of cattle, and invades the lower respiratory tract in
      stressed and/or virally infected cattle by mechanisms that are not completely
      understood. However, not all M. haemolytica appear to be equally pathogenic to
      cattle. Thus, a test could be developed to distinguish M. haemolytica genetic
      subtypes by their propensity to cause respiratory disease, allowing isolation
      and/or treatment of cattle harboring strains with an increased propensity to
      cause disease. To that end, the genomes of over 300 M. haemolytica strains are
      being sequenced. 

PMID- 25381880
TI  - Endogenous florendoviruses are major components of plant genomes and hallmarks of
      virus evolution.
AB  - The extent and importance of endogenous viral elements have been extensively
      described in animals but are much less well understood in plants. Here we
      describe a new genus of Caulimoviridae called 'Florendovirus', members of which
      have colonized the genomes of a large diversity of flowering plants, sometimes at
      very high copy numbers (>0.5% total genome content). The genome invasion of Oryza
      is dated to over 1.8 million years ago (MYA) but phylogeographic evidence points
      to an even older age of 20-34 MYA for this virus group. Some appear to have had a
      bipartite genome organization, a unique characteristic among viral retroelements.
      In Vitis vinifera, 9% of the endogenous florendovirus loci are located within
      introns and therefore may influence host gene expression. The frequent colocation
      of endogenous florendovirus loci with TA simple sequence repeats, which are
      associated with chromosome fragility, suggests sequence capture during repair of
      double-stranded DNA breaks. 

PMID- 25381882
TI  - Hereditary breast cancer syndromes and genetic testing.
AB  - Only 5% of breast cancers are explained by highly penetrant multisystem autosomal
      dominant hereditary disorders. Though another 20-30% has a familial presentation,
      the genetic and other etiologies are still not well understood. Genetic testing
      is now widely available and multiple professional societies have published
      guidelines for testing and management. Genetic testing trends include utilization
      of multi-gene panels that take advantage of next-generation sequencing as well as
      testing for low- and moderate-penetrance susceptibility genes.

PMID- 25381883
TI  - A novel ruthenium-catalyzed dehydrogenative synthesis of 2-arylquinazolines from
      2-aminoaryl methanols and benzonitriles.
AB  - By employing a commercially available Ru3(CO)12/Xantphos/t-BuOK catalyst system,
      a novel and straightforward ruthenium-catalyzed dehydrogenative synthesis of 2
      arylquinazolines has been demonstrated. A series of 2-aminoaryl methanols were
      efficiently converted in combination with different types of benzonitriles into
      various desired products in moderate to good yields upon isolation. The synthetic
      protocol proceeds with the advantages of operational simplicity, high atom
      efficiency, broad substrate scope, and no need for the use of less
      environmentally benign halogenated reagents, offering an important basis for
      accessing 2-arylquinazolines. 

PMID- 25381879
TI  - Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1
      mice.
AB  - OBJECTIVE: To investigate miR-155 in the SOD1 mouse model and human sporadic and
      familial amyotrophic lateral sclerosis (ALS). METHODS: NanoString microRNA,
      microglia and immune gene profiles, protein mass spectrometry, and RNA-seq
      analyses were measured in spinal cord microglia, splenic monocytes, and spinal
      cord tissue from SOD1 mice and in spinal cord tissue of familial and sporadic
      ALS. miR-155 was targeted by genetic ablation or by peripheral or centrally
      administered anti-miR-155 inhibitor in SOD1 mice. RESULTS: In SOD1 mice, we found
      loss of the molecular signature that characterizes homeostatic microglia and
      increased expression of miR-155. There was loss of the microglial molecules
      P2ry12, Tmem119, Olfml3, transcription factors Egr1, Atf3, Jun, Fos, and Mafb,
      and the upstream regulators Csf1r, Tgfb1, and Tgfbr1, which are essential for
      microglial survival. Microglia biological functions were suppressed including
      phagocytosis. Genetic ablation of miR-155 increased survival in SOD1 mice by 51
      days in females and 27 days in males and restored the abnormal microglia and
      monocyte molecular signatures. Disease severity in SOD1 males was associated with
      early upregulation of inflammatory genes, including Apoe in microglia. Treatment
      of adult microglia with apolipoprotein E suppressed the M0-homeostatic unique
      microglia signature and induced an M1-like phenotype. miR-155 expression was
      increased in the spinal cord of both familial and sporadic ALS. Dysregulated
      proteins that we identified in human ALS spinal cord were restored in SOD1(G93A)
      /miR-155(-/-) mice. Intraventricular anti-miR-155 treatment derepressed
      microglial miR-155 targeted genes, and peripheral anti-miR-155 treatment
      prolonged survival. INTERPRETATION: We found overexpression of miR-155 in the
      SOD1 mouse and in both sporadic and familial human ALS. Targeting miR-155 in SOD1
      mice restores dysfunctional microglia and ameliorates disease. These findings
      identify miR-155 as a therapeutic target for the treatment of ALS.

PMID- 25381884
TI  - Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones.
AB  - Quinolones exhibit good antibacterial activity against Salmonella spp. isolates
      and are often the choice of treatment for life-threatening salmonellosis due to
      multi-drug resistant strains. To assess the properties of quinolones, we
      performed an in vitro assay to study the antibacterial activities of quinolones
      against recombinant DNA gyrase. We expressed the S. Typhimurium DNA gyrase A
      (GyrA) and B (GyrB) subunits in Escherichia coli. GyrA and GyrB were obtained at
      high purity (>95%) by nickel-nitrilotriacetic acid agarose resin column
      chromatography as His-tagged 97-kDa and 89-kDa proteins, respectively. Both
      subunits were shown to reconstitute an ATP-dependent DNA supercoiling activity.
      Drug concentrations that suppressed DNA supercoiling by 50% (IC50 s) or generated
      DNA cleavage by 25% (CC25 s) demonstrated that quinolones highly active against
      S. Typhimurium DNA gyrase share a fluorine atom at C-6. The relationships between
      the minimum inhibitory concentrations (MICs), IC50 s and CC25 s were assessed by
      estimating a linear regression between two components. MICs measured against S.
      Typhimurium NBRC 13245 correlated better with IC50 s (R = 0.9988) than CC25 s (R
      = 0.9685). These findings suggest that the DNA supercoiling inhibition assay may
      be a useful screening test to identify quinolones with promising activity against
      S. Typhimurium. The quinolone structure-activity relationship demonstrated here
      shows that C-8, the C-7 ring, the C-6 fluorine, and N-1 cyclopropyl substituents
      are desirable structural features in targeting S. Typhimurium gyrase.

PMID- 25381885
TI  - Mononuclear iridium dinitrogen complexes bonded to zeolite HY.
AB  - The adsorption of N2 on structurally well-defined dealuminated HY zeolite
      supported iridium diethylene complexes was investigated. Iridium dinitrogen
      complexes formed when the sample was exposed to N2 in H2 at 298 K, as shown by
      infrared spectra recorded with isotopically labeled N2 . Four supported species
      formed in various flowing gases: Ir(N2 ), Ir(N2 )(N2 ), Ir(C2 H5 )(N2 ), and
      Ir(H)(N2 ). Their interconversions are summarized in a reaction network, showing,
      for example, that, in the presence of N2 , Ir(N2 ) was the predominant dinitrogen
      species at temperatures of 273-373 K. Ir(CO)(N2 ) formed transiently in flowing
      CO, and in the presence of H2 , rather stable iridium hydride complexes formed.
      Four structural models of each iridium complex bonded at the acidic sites of the
      zeolite were employed in a computational investigation, showing that the
      calculated vibrational frequencies agree well with experiment when full
      calculations are done at the level of density functional theory, independent of
      the size of the model of the zeolite. 

PMID- 25381887
TI  - A strategy to improve the energy conversion efficiency and stability of quantum
      dot-sensitized solar cells using manganese-doped cadmium sulfide quantum dots.
AB  - This article describes the effect of manganese (Mn) doping in CdS to improve the
      photovoltaic performance of quantum dot sensitized solar cells (QDSSCs). The
      performances of the QDSSCs are examined in detail using a polysulfide electrolyte
      with a copper sulfide (CuS) counter electrode. Under the illumination of one sun
      (AM 1.5 G, 100 mW cm(-2)), 10 molar% Mn-doped CdS QDSSCs exhibit a power
      conversion efficiency (eta) of 2.85%, which is higher than the value of 2.11%
      obtained with bare CdS. The improved photovoltaic performance is due to the
      impurities from Mn(2+) doping of CdS, which have an impact on the structure of
      the host material and decrease the surface roughness. The surface roughness and
      morphology of Mn-doped CdS nanoparticles can be characterised from atomic force
      microscopy images. Furthermore, the cell device based on the Mn-CdS electrode
      shows superior stability in the sulfide/polysulfide electrolyte in a working
      state for over 10 h, resulting in a highly reproducible performance, which is a
      serious challenge for the Mn-doped solar cell. Our finding provides an effective
      method for the fabrication of Mn-doped CdS QDs, which can pave the way to further
      improve the efficiency of future QDSSCs. 

PMID- 25381886
TI  - Protein profiling the differences between diabetic and normal mouse cumulus
      cells.
AB  - As the number of young people suffering from diabetes increases worldwide, the
      impact of this disease on human reproduction urgently needs to be addressed. Here
      we compared the proteomes of cumulus cells of super-ovulated cumulus-oocyte
      complexes from diabetic and normal mice. We identified 57 up-regulated and 74
      down-regulated proteins in diabetic cumulus cells; among these groups were
      proteins associated with cell cycle, cellular communication, epigenetic
      regulation, protein localization, and chromatin organization - all in accordance
      with type I diabetes. The poor-quality follicles derived from diabetic mice were
      further enforced by the presence of glycoproteins that are specifically expressed
      by the oocyte or oviductal epithelial cells in the cumulus-cell samples. In
      conclusion, the proteomic differences between diabetic and normal cumulus cells
      provide targets for improving the reproduction health of type I diabetic
      patients.

PMID- 25381888
TI  - Steroid hormones' genomic and non-genomic actions on cardiac voltage-gated
      calcium channels.

PMID- 25381889
TI  - Regulation of L-type Ca(2+) channels via cross-talk of Ca(2+) signaling in
      cardiac myocytes.

PMID- 25381890
TI  - Molecular mechanism of junctional membrane-targeting of cardiac and skeletal
      muscle L-type calcium channels.

PMID- 25381891
TI  - Regulation of L-type (CaV1.2) Ca(2+) channels by calmodulin and ATP.

PMID- 25381892
TI  - Pharmacological mechanisms of long-term synaptic plasticity inductions in
      prefrontal neurons.

PMID- 25381893
TI  - Cryptides: biologically active peptides hidden in protein structures.

PMID- 25381894
TI  - Pharmacological, pharmacodynamics, and clinical profile of prasugrel
      hydrochloride (Efient((r)) tablets 3.75 mg * 5 mg).

PMID- 25381895
TI  - Animal models of Alzheimer's disease.

PMID- 25381896
TI  - Double function of MFSD2A transporter at the blood-brain barrier.

PMID- 25381897
TI  - Tumour budding is associated with hypoxia at the advancing front of colorectal
      cancer.
AB  - AIMS: The tumour budding ability to predict cancer progression is felt to be
      worthy of investigation with regard to its biological properties. This study was
      aimed at evaluating the role of hypoxia and microvascularization in the
      morphogenesis of tumour budding in colorectal carcinoma. METHODS AND RESULTS: The
      immunohistochemical expression of hypoxia-inducible factor-1alpha (HIF-1alpha)
      and carbonic anhydrase IX in cancer cells and CD105 in carcinoma-induced
      microvascularization were assessed in 479 colorectal cancers. Furthermore, MET
      proto-oncogene, receptor tyrosine kinase (MET) gene amplification was searched
      using fluorescence in-situ hybridization (FISH). Carbonic anhydrase IX and HIF
      1alpha overall scores differed significantly in low- compared to high-grade
      tumour budding cancers (P < 0.001), both in pT1 and in pT2-4 tumours. Intratumour
      analysis of budding foci showed a striking absence of carbonic anhydrase IX
      immunostain in detaching cells with respect to the surrounding microsectors. The
      mean microvessel density values were significantly higher in the low- compared to
      the high-grade tumour budding groups (P < 0.001). A similar copy number of MET
      gene was detected in the two groups. CONCLUSIONS: Our study shows that tumour
      budding is associated with hypoxia induced by hypovascularization at the
      advancing front of colorectal cancer and that budding cells express a HIF-1alpha
      mediated hypoxic tumour phenotype. MET gene amplification is not related to
      tumour budding morphogenesis.

PMID- 25381898
TI  - Efficacy and safety of oral ketamine for the relief of intractable chronic pain:
      A retrospective 5-year study of 51 patients.
AB  - BACKGROUND: This work summarizes the efficiency, failures and adverse effects of
      oral administration of ketamine at home for intractable pain. METHODS: This 5
      year retrospective study involved testing ketamine by intravenous in-hospital
      administration, then a conversion to an oral route, or oral treatment directly
      administered at home. The daily intravenous dose was increased by steps of 0.5
      mg/kg to attain an effective daily dose of 1.5-3.0 mg/kg. Pain was evaluated on a
      numeric scale from 0 to 10, and evidence of adverse effects was collected every
      day. The effective daily dose was delivered orally (three to four intakes). If
      effective, ketamine was continued for 3 months. Short infusions or direct oral
      treatment began with a 0.5-mg/kg dose, then the daily ketamine dose was increased
      in 15- to 20-mg increments. RESULTS: Among 55 cases (51 patients, neuropathic
      pain 60%), the mean effective oral dose was 2 mg/kg. Ketamine was effective in 24
      patients (44%, mean pain reduction 67 +/- 17%), partially effective in 20% (mean
      pain reduction 30 +/- 11%), with a mean opioid sparing of 63 +/- 32%, and failure
      in 22%. Half of the patients experienced adverse effects, but only eight had to
      stop treatment. For patients with opioid therapy, failure of ketamine was less
      frequent (7% vs. 36%; p < 0.02), with fewer adverse effects (33% vs. 68%; p <
      0.01). CONCLUSIONS: Pain was reduced or abolished in two-thirds of patients under
      ketamine therapy; ketamine was effective for patients taking opioids and resulted
      in few adverse effects.

PMID- 25381899
TI  - Thermal decomposition mechanisms of alkylimidazolium ionic liquids with cyano
      functionalized anions.
AB  - Because of the unusually high heats of vaporization of room-temperature ionic
      liquids (RTILs), volatilization of RTILs through thermal decomposition and
      vaporization of the decomposition products can be significant. Upon heating of
      cyano-functionalized anionic RTILs in vacuum, their gaseous products were
      detected experimentally via tunable vacuum ultraviolet photoionization mass
      spectrometry performed at the Chemical Dynamics Beamline 9.0.2 at the Advanced
      Light Source. Experimental evidence for di- and trialkylimidazolium cations and
      cyano-functionalized anionic RTILs confirms thermal decomposition occurs
      primarily through two pathways: deprotonation of the cation by the anion and
      dealkylation of the imidazolium cation by the anion. Secondary reactions include
      possible cyclization of the cation and C2 substitution on the imidazolium, and
      their proposed reaction mechanisms are introduced here. Additional evidence
      supporting these mechanisms was obtained using thermal gravimetric analysis-mass
      spectrometry, gas chromatography-mass spectrometry, and temperature-jump infrared
      spectroscopy. In order to predict the overall thermal stability in these ionic
      liquids, the ability to accurately calculate both the basicity of the anions and
      their nucleophilicity in the ionic liquid is critical. Both gas phase and
      condensed phase (generic ionic liquid (GIL) model) density functional theory
      calculations support the decomposition mechanisms, and the GIL model could
      provide a highly accurate means to determine thermal stabilities for ionic
      liquids in general. 

PMID- 25381900
TI  - Personalized treatment of EGFR mutant and ALK-positive patients in NSCLC.
AB  - INTRODUCTION: The epidermal growth factor receptor (EGFR) is mutated in 15% of
      adenocarcinomas of the lung. In addition, the anaplastic lymphoma kinase (ALK) is
      altered in 8% of adenocarcinomas of the lung. Treatment of EGFR mutant and ALK
      translocation-positive tumors in NSCLC with tyrosine kinase inhibitors (TKI)
      results in a dramatic therapeutic response and has revolutionized therapy.
      Unfortunately, resistance to TKIs invariably develops. Many promising new
      therapies are under investigation to overcome the resistance. AREAS COVERED: We
      analyzed the current primary literature and recent national meetings to evaluate
      the clinical characteristics and therapeutic implications of relevant treatments
      for EGFR mutant and ALK-positive NSCLC in the first-line, acquired resistance,
      and adjuvant settings. EXPERT OPINION: Treatment with EGFR TKIs in the first-line
      setting of EGFR mutant NSCLC results in a significant clinical benefit. Several
      promising third generation EGFR TKIs are being evaluated in Phase II and III
      trials in the acquired resistance setting. Crizotinib is superior to chemotherapy
      in the first-line setting for ALK-positive NSCLC. Ceritinib is effective and
      approved for ALK-positive NSCLC in the acquired resistance setting. Continued
      investigation is needed to develop novel therapies to overcome acquired
      resistance to TKIs.

PMID- 25381901
TI  - Geometrically restricted intermediates in the self-assembly of an M12L24
      cuboctahedral complex.
AB  - The self-assembly of a cuboctahedral M12 L24 complex is traced by time-dependent
      NMR spectroscopy and mass spectrometry. The metastable intermediate structures
      that exist during the self-assembly process are not a chaotic mixture of numerous
      species, but instead are geometrically restricted. Short-lived M8 L16 (D4d ) and
      relatively long-lived M9 L18 (D3h ) are fully characterized as major
      intermediates. Employing a ligand with a smaller bend angle (112 degrees ) allows
      these two species to be kinetically trapped and more clearly observed by NMR
      spectroscopy. X-ray crystallography shows that M9 L18 has the framework topology
      predicted by geometric discussion. 

PMID- 25381902
TI  - Dr William Novick (Founder and Medical Director of International Children's Heart
      Foundation), speaks to associate editor Dr Tom R. Karl.

PMID- 25381903
TI  - Unusual food allergy: Alioidea allergic reactions overview.
AB  - Allergic reactions can cause by several aliments and foods. Symptoms usually
      appear after ingestion, several hours after consumption or even almost
      immediately. Various food allergies can lead to serious diseases and in some
      cases to death, so the priority for people suffering from them should be
      prevention and completely avoiding foods that cause this kind of reactions.
      Allergy to Alioidea is one of the probable causes of contact dermatitis, gingival
      and oculonasal diseases and asthma. In this review, we will focus on the
      increasing incidence of allergy to foods of common use like onions and garlic. In
      the last ten years, the world production of onions and garlic has increased of at
      least 25%. People make large use of them, not only in cookery but also from a
      therapeutic point of view. Their growing use is producing more and more specific,
      insidious and sometimes serious medical conditions, which highly influence the
      quality of life of patients. Medical practitioners should be able to recognize
      immediately these disorders in order to diagnose them quickly and accurately,
      avoiding unnecessary tests and treatments. We will also describe new patents for
      detecting food allergens. 

PMID- 25381904
TI  - Hepatic encephalopathy: cause and possible management with botanicals.
AB  - Hepatic encephalopathy is a brain functional disorder, characterized by
      neuropsychiatric abnormalities with liver failure. High blood ammonia, causing
      glutamate neurotoxicity is the basic cause, finally leading to low-grade cerebral
      edema. Its manifestation is more likely in patients of sepsis, oxidative stress,
      generalized inflammation, gut mal-functioning, amoebiaesis, viral hepatitis,
      nervous imbalance, etc. Thus, the therapeutic goals primarily include the
      maintenance of proper blood supply and prevention of hypoxic condition in liver,
      along with management of factors responsible for high blood ammonia, oxidative
      stress, inflammation, and high GI- serotonin. The drugs in clinical practice
      include lactulose, sodium benzoate, flumazenil and rifaximin, supplementation of
      zinc, branched chain amino acids (BCAA), l-ornithine-l aspartate, antioxidants
      and iNOS inhibitors. However, herbal formulations would be of great importance as
      it shows multi-targeted action because it possesses a natural cocktail of
      secondary metabolites. It can collectively act as an antioxidant, anti
      inflammatory, prebiotic, hepatoprotective and neuron-protective agents. We have
      briefly outlined some of these plants and also recent patents useful in the
      management of hepatic encephalopathy. 

PMID- 25381906
TI  - Retracted: Spontaneous rectus sheath haematoma associated with rivaroxaban
      treatment.
AB  - http://onlinelibrary.wiley.com/doi/10.1111/jcpt.12228/pdf The above article,
      published online on 10 November 2014 in Wiley Online Library
      (wileyonlinelibrary.com), has been retracted by agreement between the authors,
      the journal Editor in Chief, A. Li Wan Po, and John Wiley & Sons Ltd. The
      retraction has been agreed because, unknown to the authors, another group
      published a similar study based on the same material in the Indian Journal of
      Pharmacology: Kocayigit I, Can Y, Sahinkus S, et al. Spontaneous rectus sheath
      haematoma during rivaroxaban therapy. Indian Journal of Pharmacology.
      2014;46(3):339-340. doi:10.4103/0253-7613.132193. 

PMID- 25381905
TI  - Endoplasmic reticulum stress in adipose tissue augments lipolysis.
AB  - The endoplasmic reticulum (ER) is an organelle important for protein synthesis
      and folding, lipid synthesis and Ca(2+) homoeostasis. Consequently, ER stress or
      dysfunction affects numerous cellular processes and has been implicated as a
      contributing factor in several pathophysiological conditions. Tunicamycin induces
      ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark
      of tunicamycin administration is the development of fatty livers within 24-48 hrs
      accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce
      ER stress in adipose tissue that would lead to increased lipolysis and
      subsequently to fatty infiltration of the liver and hepatomegaly. Our results
      show that intraperitoneal administration of tunicamycin rapidly induced an ER
      stress response in adipose tissue that correlated with increased circulating free
      fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and
      lipid droplet size. Furthermore, we found that in addition to fatty infiltration
      of the liver as well as hepatomegaly, lipid accumulation was also present in the
      heart, skeletal muscle and kidney. To corroborate our findings to a clinical
      setting, we examined adipose tissue from burned patients where increases in
      lipolysis and the development of fatty livers have been well documented. We found
      that burned patients displayed significant ER stress within adipose tissue and
      that ER stress augments lipolysis in cultured human adipocytes. Our results
      indicate a possible role for ER stress induced lipolysis in adipose tissue as an
      underlying mechanism contributing to increases in circulating FFAs and fatty
      infiltration into other organs.

PMID- 25381907
TI  - Mannose-modified chitosan microspheres enhance OprF-OprI-mediated protection of
      mice against Pseudomonas aeruginosa infection via induction of mucosal immunity.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that localizes to and
      colonizes mucosal tissue. Thus, vaccines that elicit a strong mucosal response
      against P. aeruginosa should be superior to other vaccination strategies. In this
      study, to stimulate rapid and enhanced mucosal immune responses, mannose-modified
      chitosan microspheres loaded with the recombinant outer membrane protein OprF190
      342-OprI21-83 (FI) (FI-MCS-MPs) of P. aeruginosa were developed as a potent
      subunit vaccine for mucosal delivery. FI-MCS-MPs were successfully obtained via
      the tripolyphosphate ionic crosslinking method. Confocal and immunohistochemical
      analyses indicated that FI-MCS-MPs exhibited the ability to bind the macrophage
      mannose receptor (MMR, CD206) in vitro and in vivo. After intranasal immunization
      of mice with FI-MCS-MPs, FI-specific humoral immune responses were detected,
      measured as local IgM antibody titers in lung tissue slurry; IgA antibody titers
      in nasal washes, bronchoalveolar lavage (BAL), and intestinal lavage; and
      systemic IgA and IgG antibody titers in serum. FI-MCS-MPs induced early and high
      mucosal and systemic humoral antibody responses comparable to those in the group
      vaccinated with unmodified mannose. High levels of IFN-gamma and IL-4 in addition
      to T lymphocyte subsets induced a mixed Th1/Th2 response in mice immunized with
      FI-MCS-MPs, resulting in the establishment of cellular immunity. Additionally,
      when immunized mice were challenged with P. aeruginosa via the nasal cavity, FI
      MCS-MPs demonstrated 75 % protective efficacy. Together, these data indicate that
      mannose-modified chitosan microspheres are a promising subunit delivery system
      for vaccines against P. aeruginosa infection.

PMID- 25381908
TI  - Ammonia-oxidizing archaea versus bacteria in two soil aquifer treatment systems.
AB  - So far, the contribution of ammonia-oxidizing archaea (AOA) to ammonia oxidation
      in wastewater treatment processes has not been well understood. In this study,
      two soil aquifer treatment (SATs) systems were built up to treat synthetic
      domestic wastewater (column 1) and secondary effluent (column 4), accomplishing
      an average of 95% ammonia removal during over 550 days of operation. Except at
      day 322, archaeal amoA genes always outnumbered bacterial amoA genes in both SATs
      as determined by using quantitative polymerase chain reaction (q-PCR). The ratios
      of archaeal amoA to 16S rRNA gene averaged at 0.70 +/- 0.56 and 0.82 +/- 0.62 in
      column 1 and column 4, respectively, indicating that all the archaea could be AOA
      carrying amoA gene in the SATs. The results of MiSeq-pyrosequencing targeting on
      archaeal and bacterial 16S rRNA genes with the primer pair of modified 515R/806R
      indicated that Nitrososphaera cluster affiliated with thaumarchaeal group I.1b
      was the dominant AOA species, while Nitrosospira cluster was the dominant ammonia
      oxidizing bacteria (AOB). The statistical analysis showed significant
      relationship between AOA abundance (compared to AOB abundance) and inorganic and
      total nitrogen concentrations. Based on the mathematical model calculation for
      microbial growth, AOA had much greater capacity of ammonia oxidation as compared
      to the specific influent ammonia loading for AOA in the SATs, implying that a
      small fraction of the total AOA would actively work to oxidize ammonia
      chemoautotrophically whereas most of AOA would exhibit some level of functional
      redundancy. These results all pointed that AOA involved in microbial ammonia
      oxidation in the SATs.

PMID- 25381909
TI  - A practical approach for O-linked mannose removal: the use of recombinant
      lysosomal mannosidase.
AB  - The methylotrophic yeast Pichia pastoris is an attractive expression system due
      to its ability to secrete large amounts of recombinant protein, with the
      potential for glycosylation. Advances in glycoengineering of P. pastoris have
      successfully demonstrated the humanization of both the N- and O-linked
      glycosylation pathways in this organism. However, in certain cases, the presence
      of O-linked glycans on a therapeutic protein may not be desirable. Recently, we
      have reported the in vitro utility of jack bean alpha-1,2/3/6-mannosidase to
      remove O-linked mannose from intact undenatured glycoproteins produced in
      glycoengineered P. pastoris. However, one caveat of this strategy is that jack
      bean mannosidase has yet to be cloned and as such is only available as crude
      cellular extracts. This raises several concerns for using this reagent to treat
      large preparations of therapeutic proteins generated in P. pastoris. Therefore,
      we postulated that lysosomal mannosidases which have been cloned and demonstrated
      to have similar activities to jack bean mannosidase on N-linked glycans would
      also process O-linked glycans in a similar fashion. To this end, we screened a
      panel of recombinant lysosomal mannosidases from different organisms and
      identified several which cannot only reduce extended O-linked mannose chains but
      which can also hydrolyze the Man-alpha-O-Ser/Thr glycosidic bond on intact
      glycoproteins. As such, not only do we show for the first time the utility of
      lysosomal mannosidase for O-linked mannose processing, but since this is a
      recombinant enzyme, it has several benefits over the use of crude jack bean
      mannosidase extracts.

PMID- 25381910
TI  - Cellulose production and cellulose synthase gene detection in acetic acid
      bacteria.
AB  - The ability of acetic acid bacteria (AAB) to produce cellulose has gained much
      industrial interest due to the physical and chemical characteristics of bacterial
      cellulose. The production of cellulose occurs in the presence of oxygen and in a
      glucose-containing medium, but it can also occur during vinegar elaboration by
      the traditional method. The vinegar biofilm produced by AAB on the air-liquid
      interface is primarily composed of cellulose and maintains the cells in close
      contact with oxygen. In this study, we screened for the ability of AAB to produce
      cellulose using different carbon sources in the presence or absence of ethanol.
      The presence of cellulose in biofilms was confirmed using the fluorochrome
      Calcofluor by microscopy. Moreover, the process of biofilm formation was
      monitored under epifluorescence microscopy using the Live/Dead BacLight Kit. A
      total of 77 AAB strains belonging to 35 species of Acetobacter, Komagataeibacter,
      Gluconacetobacter, and Gluconobacter were analysed, and 30 strains were able to
      produce a cellulose biofilm in at least one condition. This cellulose production
      was correlated with the PCR amplification of the bcsA gene that encodes cellulose
      synthase. A total of eight degenerated primers were designed, resulting in one
      primer pair that was able to detect the presence of this gene in 27 AAB strains,
      26 of which formed cellulose. 

PMID- 25381911
TI  - alpha-N-Acetylglucosaminidase from Bifidobacterium bifidum specifically
      hydrolyzes alpha-linked N-acetylglucosamine at nonreducing terminus of O-glycan
      on gastric mucin.
AB  - alpha-Linked N-acetylglucosamine is one of the major glyco-epitopes in O-glycan
      of gastroduodenal mucin. Here, we identified glycoside hydrolase (GH) family 89
      alpha-N-acetylglucosaminidase, termed AgnB, from Bifidobacterium bifidum JCM
      1254, which is essentially specific to GlcNAcalpha1-4Gal structure. AgnB is a
      membrane-anchored extracellular enzyme consisting of a GH89 domain and four
      carbohydrate-binding module (CBM) 32 domains. Among four CBM32 domains, three
      tandem ones at C-terminus showed to bind porcine gastric mucin, suggesting that
      these domains enhance the enzyme activity by increasing affinity for multivalent
      substrates. AgnB might be important for assimilation of gastroduodenal mucin by
      B. bifidum and also applicable to production of prebiotic oligosaccharides from
      porcine gastric mucin.

PMID- 25381912
TI  - Nanowastes treatment in environmental media.
AB  - OBJECTIVES: This paper tried to review a recent research trend for the
      environmental exposure of engineered nanomaterials (ENMs) and its removal
      efficiency in the nanowaste treatment plants. METHODS: The studies on the
      predicted environmental concentrations (PEC) of ENMs obtained by exposure
      modeling and treatment (or removal) efficiency in nanowaste treatment facilities,
      such as wastewater treatment plant (WTP) and waste incineration plant (WIP) were
      investigated. The studies on the landfill of nanowastes also were investigated.
      RESULTS: The Swiss Federal Laboratories for Materials Science and Technology
      group has led the way in developing methods for estimating ENM production and
      emissions. The PEC values are available for surface water, wastewater treatment
      plant effluents, biosolids, sediments, soils, and air. Based on the PEC modeling,
      the major routes for the environmental exposure of the ENMs were found as WTP
      effluents/sludge. The ENMs entered in the WTP were 90-99% removed and accumulated
      in the activated sludge and sludge cake. Additionally, the waste ash released
      from the WIP contain ENMs. Ultimately, landfills are the likely final destination
      of the disposed sludge or discarded ENMs products. CONCLUSIONS: Although the
      removal efficiency of the ENMs using nanowaste treatment facilities is
      acceptable, the ENMs were accumulated on the sludge and then finally moved to the
      landfill. Therefore, the monitoring for the ENMs in the environment where the WTP
      effluent is discharged or biomass disposed is required to increase our knowledge
      on the fate and transport of the ENMs and to prevent the unintentional exposure
      (release) in the environment.

PMID- 25381913
TI  - Licochalcone A activates Nrf2 in vitro and contributes to licorice extract
      induced lowered cutaneous oxidative stress in vivo.
AB  - The retrochalcone licochalcone A (LicA) has previously been shown to possess
      antimicrobial and anti-inflammatory properties. In this study, we focused on
      pathways responsible for the antioxidative properties of LicA. In vitro, LicA
      protected from oxidative stress mediated by reactive oxygen species (ROS) by
      activating the expression of cytoprotective phase II enzymes. LicA induced
      nuclear translocation of NF-E2-related factor 2 (Nrf2) in primary human
      fibroblasts and elevated the expression of the cytoprotective and anti
      inflammatory enzymes heme oxygenase 1 and glutamate-cysteine ligase modifier
      subunit. LicA-treated cells displayed a higher ratio of reduced to oxidized
      glutathione and decreased concentrations of ROS in UVA-irradiated human dermal
      fibroblasts, as well as in activated neutrophils. In vivo, ultraweak photon
      emission analysis of skin treated with LicA-rich licorice extract revealed a
      significantly lowered UVA-induced luminescence, indicative for a decrease in
      oxidative processes. We conclude from these data that topical application of
      licorice extract is a promising approach to induce Nrf2-dependent cytoprotection
      in human skin. 

PMID- 25381914
TI  - Prophylactic intracameral antibiotic use during cataract surgery.

PMID- 25381915
TI  - Factors influencing ceftriaxone use in community-acquired pneumonia: Emergency
      doctors' perspectives.
AB  - OBJECTIVE: To explore the perceptions of ED doctors regarding the use of
      ceftriaxone in patients with community-acquired pneumonia (CAP). METHODS: Face-to
      face interviews were conducted with ED doctors in an Australian tertiary public
      hospital. A semi-structured interview method was used for collecting data and a
      framework analysis approach utilised to identify emerging themes regarding the
      influences on ED prescribers when using ceftriaxone for CAP. RESULTS: Eight
      interviews were performed (two consultants, four registrars and two residents).
      Five main themes emerged as influencing decisions regarding the selection of
      ceftriaxone for patients with CAP: (i) clinical intuition versus structured
      evaluation of severity; (ii) clinical uncertainty; (iii) prior experience; (iv)
      source of guidance; and (v) prescribing etiquette. CONCLUSION: As most cases of
      CAP are initially diagnosed and treated empirically in the ED, any interventions
      that aim to decrease inappropriate use of ceftriaxone for CAP should address the
      factors identified here that influence ED doctors' prescribing decisions.

PMID- 25381916
TI  - Is it congenital or acquired von Willebrands disease?

PMID- 25381917
TI  - A novel interface for the telementoring of robotic surgery.
AB  - OBJECTIVE: To prospectively evaluate the feasibility and safety of a novel,
      second-generation telementoring interface (Connect(TM) ; Intuitive Surgical Inc.,
      Sunnyvale, CA, USA) for the da Vinci robot. MATERIALS AND METHODS: Robotic
      surgery trainees were mentored during portions of robot-assisted prostatectomy
      and renal surgery cases. Cases were assigned as traditional in-room mentoring or
      remote mentoring using Connect. While viewing two-dimensional, real-time video of
      the surgical field, remote mentors delivered verbal and visual counsel, using two
      way audio and telestration (drawing) capabilities. Perioperative and technical
      data were recorded. Trainee robotic performance was rated using a validated
      assessment tool by both mentors and trainees. The mentoring interface was rated
      using a multi-factorial Likert-based survey. The Mann-Whitney and t-tests were
      used to determine statistical differences. RESULTS: We enrolled 55 mentored
      surgical cases (29 in-room, 26 remote). Perioperative variables of operative time
      and blood loss were similar between in-room and remote mentored cases. Robotic
      skills assessment showed no significant difference (P > 0.05). Mentors preferred
      remote over in-room telestration (P = 0.05); otherwise no significant difference
      existed in evaluation of the interfaces. Remote cases using wired (vs wireless)
      connections had lower latency and better data transfer (P = 0.005). Three of 18
      (17%) wireless sessions were disrupted; one was converted to wired, one continued
      after restarting Connect, and the third was aborted. A bipolar injury to the
      colon occurred during one (3%) in-room mentored case; no intraoperative injuries
      were reported during remote sessions. CONCLUSION: In a tightly controlled
      environment, the Connect interface allows trainee robotic surgeons to be
      telementored in a safe and effective manner while performing basic surgical
      techniques. Significant steps remain prior to widespread use of this technology.

PMID- 25381918
TI  - Kinetic behaviour of Staphylococcus aureus on cheese as a function of water
      activity and temperature.
AB  - This study developed mathematical models in order to evaluate the effect of Aw
      (Water activity) and growth temperature on Staphylococcus aureus kinetic
      behaviour. The Aw levels (0.970, 0.975, 0.983, and 0.991) of cheese were adjusted
      by NaCl; then, Staph. aureus was inoculated on the cheese, followed by storage at
      7-30  degrees C for 72-720 h. Total bacterial and Staph. aureus cell counts were
      enumerated on tryptic soy agar and mannitol salt agar, respectively. The Baranyi
      model was fitted to the Staph. aureus growth data in order to calculate the
      maximum specific growth rate (MUmax; log CFU/g/h), lag phase duration (lambda;
      h), lower asymptote (N0; log CFU/g) and upper asymptote (Nmax; log CFU/g). The
      effects of storage temperature and Aw on the kinetic parameters (MUmax and
      lambda) were then further analysed with the Ratkowsky-type model and a polynomial
      equation, respectively. The root mean square error (RMSE) and relative error (RE)
      were calculated in order to estimate the model performance. No significant effect
      of Aw on Staph. aureus growth was observed at 7  degrees C; thus, the Baranyi
      model was fitted to the growth data from 15, 25 and 30  degrees C. The MUmax
      values (0.011-0.303 log CFU/g/h) increased (P<0.05) as the storage temperature
      and Aw increased. In addition, lambda values (2.42-63.48 h) decreased (P<0.05) as
      storage temperature and Aw increased; yet, the effect of Aw on lambda was
      observed only at 15  degrees C. The theoretical minimum storage temperature and
      Aw were 10.15  degrees C and 0.882, respectively. RMSE (0.010-1.544) and RE
      values (-0.131 to 0.187) from validation indicated that model performance was
      appropriate. Hence, these results suggest that the developed models in this study
      should be useful in describing the effect of temperature and Aw on the growth
      kinetic behaviour of Staph. aureus in cheese along with the exposure assessment
      of Staph. aureus in cheese as well.

PMID- 25381919
TI  - Classification of pelvic ring fractures in skeletonized human remains.
AB  - Pelvic ring fractures are associated with high rates of mortality and thus can
      provide key information about circumstances surrounding death. These injuries can
      be particularly informative in skeletonized remains, yet difficult to diagnose
      and interpret. This study adapted a clinical system of classifying pelvic ring
      fractures according to their resultant degree of pelvic stability for application
      to gross human skeletal remains. The modified Tile criteria were applied to the
      skeletal remains of 22 individuals from the Cleveland Museum of Natural History
      and Universidad Nacional Autonoma de Mexico that displayed evidence of pelvic
      injury. Because these categories are tied directly to clinical assessments
      concerning the severity and treatment of injuries, this approach can aid in the
      identification of manner and cause of death, as well as interpretations of
      possible mechanisms of injury, such as those typical in car-to-pedestrian and
      motor vehicle accidents. 

PMID- 25381920
TI  - The importance of paediatric nutrition.
AB  - This articles looks at infant nutrition, from birth and through the first year of
      life. Good quality foods in infancy and childhood do not only promote optimum
      growth and development during that time, but also play a role in helping to
      prevent obesity and some diseases of adulthood, particularly non-communicable
      diseases, such as heart disease, type 2 diabetes and some cancers. Ensuring a
      good nutritional start for the paediatric population will help reduce morbidity
      and mortality later in life. 

PMID- 25381921
TI  - Natural cholesterol-lowering products: focus on probiotics.
AB  - It is important to maintain healthy blood lipid profiles in order to reduce risk
      of cardiovascular disease. This article explores some of the evidence for natural
      cholesterol lowering products as a possible alternative to cholesterol lowering
      medication. Probiotics have been investigated for their effect on cholesterol
      levels and there is increasing evidence to support their use as a natural
      cholesterol lowering alternative. 

PMID- 25381922
TI  - Adult enteral device selection: which is the best for the patient?
AB  - Enteral feeding is considered to be a safe and effective way of providing
      nutrition to patients who are unable to meet their requirements orally. There are
      a number of enteral feeding devices, including naso-gastric and gastrostomy
      tubes, that allow access to the stomach for feeding. However, selecting the most
      appropriate device for a patient depends on a number of factors, including
      consideration of duration of feeding and the individual patient's clinical
      condition and social circumstances. In addition, the patient should always be
      included in decision making where possible. This article explores the decision
      making process regarding selection of appropriate enteral feeding devices and
      applies this process to two patient case studies. 

PMID- 25381923
TI  - Nutrition and dementia: what can we do to help?
AB  - This review explores dementia progression and links to how the nutritional status
      of a person with dementia may be affected. It will also consider what health
      professionals based in community can do to maximise the nutritional status of the
      person with dementia. Practical, holistic suggestions-covering small appetite,
      communication difficulties, mood changes, swallowing problems and aversive
      mealtime behaviour-will be covered. Existing literature and current guidelines
      will be explored, common practice points around the nutritional care of people
      with dementia will be discussed, and local initiatives to help tackle
      malnutrition, particularly in those with dementia, will be highlighted. 

PMID- 25381924
TI  - Potential barriers to effective MUST implementation.
AB  - The Malnutrition Universal Screening Tool (MUST) is frequently cited as a simple
      screening tool for malnutrition. However, anecdotally, it seems that not all
      staff find it simple to use. If staff do not find MUST simple to complete, then
      screening is less likely to be completed accurately. Accurate completion of MUST
      is essential for malnutrition to be identified and treated, otherwise the
      nutritional needs of patients with unrecognised malnutrition may be neglected.
      The use of simplified versions of body mass index score, weight loss score and
      ulna-length charts together with ongoing training and support may help to improve
      accurate MUST completion. Audit of MUST completion must consider the accuracy of
      completion rather than completion alone. Therefore, those auditing MUST
      completion require a good understanding of the tool. This article draws on the
      author's own significant experience with applying the MUST tool and synthesises
      this with evidence from the literature to demonstrate the potential barriers to
      effective MUST implementation. 

PMID- 25381925
TI  - Interview with Penelope Deel-Smith.

PMID- 25381926
TI  - Improving community malnutrition.

PMID- 25381927
TI  - Nutritional management in chyle leaks and chylous effusions.
AB  - Chyle leaks occur when there is interruption to the lymphatic ducts that
      transport chyle around the body. The loss of this protein-rich, calorie-rich
      fluid can cause serious complications including dehydration, malnutrition and
      immunosuppression. Treatment of chyle leaks depends on the underlying cause,
      which may be surgical, secondary to malignant invasion or the result of a medical
      condition. Nutritional support is vital and leads to spontaneous leak closure in
      many cases. Nutritional management options include total bowel rest with
      parenteral nutrition, enteral feeding with specialized formula, or oral diet with
      supplementation. At present there is no consensus regarding which approach is
      superior. In reality, most patients with chyle leaks are managed with a
      combination or oral and enteral feeding, but further work is needed to clarify
      the optimum management strategy. 

PMID- 25381928
TI  - Disease recurrence in localized scleroderma: a retrospective analysis of 344
      patients with paediatric- or adult-onset disease.
AB  - BACKGROUND: Localized scleroderma (LoS) is characterized by a phase of disease
      activity followed by remission. However, disease recurrences occur. Knowledge
      concerning these recurrences can help prompt treatment, thereby preventing
      disease damage. OBJECTIVES: To investigate the frequency and characteristics of
      disease recurrences in paediatric- and adult-onset LoS, and to identify patient
      variables that are associated with a higher risk of disease recurrence. METHODS:
      Retrospective chart reviews were performed of patients with LoS. Data concerning
      the frequency and characteristics of the disease recurrences were collected. A
      multivariate analysis was performed to identify patient variables that were
      associated with a higher risk of disease recurrence. RESULTS: In total, 344
      patients were included in the analysis, of whom 119 (35%) had paediatric-onset
      LoS and 225 (65%) had adult-onset LoS. Disease recurrence was present in 27% (n =
      32) of the paediatric-onset group and 17% (n = 39) of the adult-onset group (P =
      0.037). Multivariate analysis identified a statistically significant association
      between disease recurrence and the linear LoS of the limbs subtype, independent
      of age at disease onset. CONCLUSIONS: Recurrences in LoS occurred in almost one
      quarter of the patients and were most frequent in the linear LoS of the limbs
      subtype, independent of age at disease onset. These disease recurrences can occur
      even after many years of quiescent disease. Awareness of the high recurrence
      rates may help treating physicians to recognize reactivation of the disease,
      leading to a decreased delay in treatment reinitiation.

PMID- 25381929
TI  - A new non-destructive readout by using photo-recovered surface potential
      contrast.
AB  - Ferroelectric random access memory is still challenging in the feature of
      combination of room temperature stability, non-destructive readout and high
      intensity storage. As a non-contact and non-destructive information readout
      method, surface potential has never been paid enough attention because of the
      unavoidable decay of the surface potential contrast between oppositely polarized
      domains. That is mainly due to the recombination of the surface movable charges
      around the domain walls. Here, by introducing a laser beam into the combination
      of piezoresponse force microscopy and Kelvin probe force microscopy, we
      demonstrate that the surface potential contrast of BiFeO3 films can be recovered
      under light illumination. The recovering mechanism is understood based on the
      redistribution of the photo-induced charges driven by the internal electric
      field. Furthermore, we have created a 12-cell memory pattern based on BiFeO3
      films to show the feasibility of such photo-assisted non-volatile and non
      destructive readout of the ferroelectric memory. 

PMID- 25381930
TI  - HEK293-based production platform for gamma-retroviral (self-inactivating)
      vectors: application for safe and efficient transfer of COL7A1 cDNA.
AB  - The clinical application of self-inactivating (SIN) retroviral vectors requires
      an efficient vector production technology. To enable production of gamma
      retroviral SIN vectors from stable producer cells, new targetable HEK293-based
      producer clones were selected, providing amphotropic, GALV, or RD114
      pseudotyping. Viral vector expression constructs can reliably be inserted at a
      predefined genomic locus via Flp-recombinase-mediated cassette exchange.
      Introduction of a clean-up step, mediated by Cre-recombinase, allows the removal
      of residual sequences that were required for targeting and selection, but were
      dispensable for the final producer clones and eliminated homology-driven
      recombination between the tagging and the therapeutic vector. The system was used
      to establish GALV and RD114 pseudotyping producer cells (HG- and HR820) for a
      clinically relevant long terminal repeat-driven therapeutic vector, designed for
      the transfer of a recombinant TCR that delivered titers in the range of 2*10(7)
      infectious particles (IP)/ml. Production capacity of the amphotropic producer
      cell (HA820) was challenged by a therapeutic SIN vector transferring the large
      COL7A1 cDNA. The final producer clone delivered a titer of 4*10(6) IP/ml and the
      vector containing supernatant was used directly to functionally restore primary
      fibroblasts and keratinocytes isolated from recessive dystrophic epidermolysis
      bullosa patients. Thus, the combinatorial approach (fc-technology) to generate
      producer cells for therapeutic gamma-retroviral (SIN) vectors is feasible, is
      highly efficient, and allows their safe production and application in clinical
      trials.

PMID- 25381931
TI  - Solid-state NMR of a protein in a precipitated complex with a full-length
      antibody.
AB  - NMR spectroscopy is a prime technique for characterizing atomic-resolution
      structures and dynamics of biomolecular complexes but for such systems faces
      challenges of sensitivity and spectral resolution. We demonstrate that the
      application of (1)H-detected experiments at magic-angle spinning frequencies of
      >50 kHz enables the recording, in a matter of minutes to hours, of solid-state
      NMR spectra suitable for quantitative analysis of protein complexes present in
      quantities as small as a few nanomoles (tens of micrograms for the observed
      component). This approach enables direct structure determination and quantitative
      dynamics measurements in domains of protein complexes with masses of hundreds of
      kilodaltons. Protein-protein interaction interfaces can be mapped out by
      comparison of the chemical shifts of proteins within solid-state complexes with
      those of the same constituent proteins free in solution. We employed this
      methodology to characterize a >300 kDa complex of GB1 with full-length human
      immunoglobulin, where we found that sample preparation by simple precipitation
      yields spectra of exceptional quality, a feature that is likely to be shared with
      some other precipitating complexes. Finally, we investigated extensions of our
      methodology to spinning frequencies of up to 100 kHz. 

PMID- 25381932
TI  - The Helicobacter pylori L-form: formation and isolation in the human bile
      cultures in vitro and in the gallbladders of patients with biliary diseases.
AB  - BACKGROUND: The Helicobacter pylori is considered the important causative agent
      causing biliary diseases, but the H. pylori can be isolated from very few
      gallbladder specimens with diseases. We studied the formation of H. pylori L
      forms in bile in vitro and isolated the H. pylori L-forms from gallbladder of
      patients with biliary diseases. METHODS: We inoculated the H. pylori into the
      human bile to induce the L-form in vitro. The gallbladder specimens were
      collected from patients with biliary diseases to isolate the bacterial L-forms by
      the nonhigh osmotic isolation technique, and the H. pylori L-forms in the L-form
      isolates were identified by the gene assay for the H. pylori-specific genes 16S
      rRNA and UreA. RESULTS: The H. Pylori cannot be isolated from the bile-induced
      cultures, but the H. pylori L-form can be isolated from the H. pylori-negative
      bile-induced cultures. The L-form isolates of bile-induced cultures showed a
      positive reaction of the H. pylori-specific genes by PCR, and the coincidence
      ratio of the nucleotide sequences between the L-forms and the H. pylori is 99%.
      The isolation rate of bacteria L-form is 93.2% in the gallbladder specimens with
      bacteria-negative isolation culture by the nonhigh osmotic isolation technique,
      and the positive rate of the H. pylori-specific genes in the L-form isolates is
      7.1% in the bacterial L-form-positive isolation cultures by the PCR. CONCLUSIONS:
      H. pylori can be rapidly induced into the L-form in the human bile; the L-form,
      as the latent bacteria, can live in the host gallbladder for a long times, and
      they made the host became a latent carrier of the H. pylori L-form. The H. pylori
      L-form can be isolated by the nonhigh osmotic isolation technique, and the
      variant can be identified by the gene assay for the H. pylori-specific genes 16S
      rRNA and reA.

PMID- 25381933
TI  - Carbohydrate-binding module tribes.
AB  - At present, 69 families of carbohydrate-binding modules (CBMs) have been isolated
      by statistically significant differences in the amino acid sequences (primary
      structures) of their members, with most members of different families showing
      little if any homology. On the other hand, members of the same family have
      primary and tertiary (three-dimensional) structures that can be computationally
      aligned, suggesting that they are descended from common protein ancestors.
      Members of the large majority of CBM families are beta-sandwiches. This raises
      the question of whether members of different families are descended from distant
      common ancestors, and therefore are members of the same tribe. We have attacked
      this problem by attempting to computationally superimpose tertiary structure
      representatives of each of the 53 CBM families that have members with known
      tertiary structures. When successful, we have aligned locations of secondary
      structure elements and determined root mean square deviations and percentages of
      similarity between adjacent amino acid residues in structures from similar
      families. Further criteria leading to tribal membership are amino acid chain
      lengths and bound ligands. These considerations have led us to assign 27 families
      to nine tribes. Eight of the tribes have members with beta-sandwich structures,
      while the ninth is composed of structures with beta-trefoils.

PMID- 25381934
TI  - Spin-crossover in phenylazopyridine-functionalized Ni-porphyrin: trans-cis
      isomerization triggered by pi-pi interactions.
AB  - Reversible, room-temperature light-induced spin-crossover has been reported in a
      Ni-porphyrin functionalized with a phenylazopyridine (PAPy) ligand (Venkataramani
      et al., Science, 2011, 331, 445). Upon light irradiation (500 nm), the
      azopyridine moiety induces a change in the Ni(II) coordination sphere from square
      planar (n = 4) to square pyramid (n = 5), leading to a change in the total spin
      of the molecule from S = 0 to S = 1. The trans-cis isomerization in the
      azopyridine ligand has been proposed to trigger the spin-crossover effect.
      However, the radiation used to induce the HS state is about 135 nm red-shifted
      with respect to the radiation used for trans-cis isomerization of the N=N double
      bond in other compounds. To elucidate the light-induced spin-crossover mechanism
      of this Ni(II) compound, a combined DFT/CASSCF/CASPT2 study has been performed to
      determine the most stable cis and trans conformers with n = 4 or n = 5, and to
      characterize the excitation that triggers the SCO process. pi-pi interactions
      between porphyrin and PAPy are shown to play an essential role in the spin
      crossover.

PMID- 25381935
TI  - Novel synthesis of 5-methyl-5,10-dihydroindolo[3,2-b]indoles by Pd-catalyzed C-C
      and two-fold C-N coupling reactions.
AB  - A series of 5,10-dihydroindolo[3,2-b]indoles was successfully prepared by an
      efficient two-step strategy based on site-selective Pd-catalyzed cross-coupling
      reaction with N-methyl-2,3-dibromoindole and subsequent cyclization by two-fold
      Pd-catalyzed C-N coupling with amines. The products show a strong fluorescence. 

PMID- 25381936
TI  - Atlantic salmon, Salmo salar L. are broadly susceptible to isolates representing
      the North American genogroups of infectious hematopoietic necrosis virus.
AB  - Beginning in 1992, three epidemic waves of infectious hematopoietic necrosis,
      often with high mortality, occurred in farmed Atlantic salmon Salmo salar L. on
      the west coast of North America. We compared the virulence of eleven strains of
      infectious hematopoietic necrosis virus (IHNV), representing the U, M and L
      genogroups, in experimental challenges of juvenile Atlantic salmon in freshwater.
      All strains caused mortality and there was wide variation within genogroups:
      cumulative mortality for five U-group strains ranged from 20 to 100%, four M
      group strains ranged 30-63% and two L-group strains varied from 41 to 81%. Thus,
      unlike Pacific salmonids, there was no apparent correlation of virulence in a
      particular host species with virus genogroup. The mortality patterns indicated
      two different phenotypes in terms of kinetics of disease progression and final
      per cent mortality, with nine strains having moderate virulence and two strains
      (from the U and L genogroups) having high virulence. These phenotypes were
      investigated by histopathology and immunohistochemistry to describe the variation
      in the course of IHNV disease in Atlantic salmon. The results from this study
      demonstrate that IHNV may become a major threat to farmed Atlantic salmon in
      other regions of the world where the virus has been, or may be, introduced. 

PMID- 25381937
TI  - Facile fabrication of carbon ultramicro- to nanoelectrode arrays with tunable
      voltammetric response.
AB  - The voltammetric response for nano- to micrometer-sized electrode arrays are
      represented by two major regimes: a sigmoidal shaped i-v response for arrays
      acting as individual electrodes in parallel and peak-shaped i-v response for
      arrays acting as an ensemble in concert. Here, we present a facile and versatile
      technique to fabricate ultramicro- to nanoelectrode arrays using atomic layer
      deposition of insulating Al2O3 on conductive carbon films masked by 1.54, 11, or
      90-MUm-diameter polystyrene spheres (PSS). The ratio between the interelectrode
      distance and the electrode radii of the electrode arrays is a predictable
      function of the PSS radius used in fabrication, resulting in electrode arrays
      with a tunable voltammetric response. Arrays are characterized utilizing cyclic
      voltammetry and electrochemical impedance spectroscopy, which provides the
      critical scan rate, nucrit, the scan rate at which the radial diffusion layers of
      the individual electrodes overlap and appear as a single linear diffusion layer.
      Thus, below nu(crit), the electrode has a peak-shaped i-v response associated
      with semi-infinite linear diffusion, whereas above this critical scan rate, the i
      v response is sigmoidal as a result of hemispherical radial diffusion. Results
      indicate that the critical scan rates are 6.6, 1.0, and 0.01 V/s for the 1.54,
      11, and 90 MUm PSS prepared electrode arrays, respectively.

PMID- 25381938
TI  - The effects of asymmetrical loading on gait characteristics.
AB  - Asymmetrical load carriage is a popular method used among people in daily life.
      This study investigated the impact of asymmetrical load carriage and the load
      mass spatiotemporal parameters associated with gait patterns. Twelve participants
      were recorded as they walked under six load conditions. The loads included a
      control condition in which individuals carried no added load and loads of 10%,
      15%, 20%, 25%, and 30% body weight carried with their right hand. Parameters used
      to describe the spatiotemporal characteristics of gait were quantified and
      analyzed. The results of the study demonstrated that the gait patterns of the
      individuals were affected by increases in the carried load. The loaded right side
      was more sensitive to changes in the loads carried. Overall, we conclude that the
      spatiotemporal parameters actually depend on the combination of both loading mass
      and the side that was loaded.

PMID- 25381939
TI  - Omega-3 polyunsaturated fatty acids enhance cytokine production and oxidative
      stress in a mouse model of preterm labor.
AB  - OBJECTIVE: Omega-3 polyunsaturated fatty acid (omega-3 PUFA) supplementation
      during pregnancy remains controversial. We sought to examine the effects of omega
      3 PUFA on inflammation and oxidative stress in vitro and in vivo using a model of
      preterm labor. METHODS: In vivo. Female Swiss Webster mice were fed a normal diet
      or a 5% fish oil (FO) diet for 3 weeks then mated with normal-fed males. On
      gestational day 15, dams were injected with either saline (n=10 per group) or
      lipopolysaccharide (LPS, intrauterine) (n=10 per group). Maternal plasma,
      amniotic fluid, placentas, and uteri were collected 4 h later and assessed for
      cytokines; maternal plasma and amniotic fluids were analyzed for oxidative
      stress. In vitro. RAW264.7 mouse macrophage-like cells were treated with either:
      vehicle, H2O2, docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) (0, 0.1
      100 MUM) and analyzed for oxidative stress. RESULTS: In vivo. Administration of
      the 5% FO diet enhanced LPS-induced cytokines in the placenta (P<0.05-0.01) and
      increased tumor necrosis factor-alpha in the uterus (P<0.05) and amniotic fluid
      (P<0.01) when compared to LPS-treated normal-fed animals. Maternal plasma
      obtained from FO-fed dams showed higher LPS-induced oxidative stress than control
      fed animals (P<0.035). However, no differences in oxidative stress were observed
      in the amniotic fluid. In vitro. Treatment of macrophage-like cells with omega-3
      PUFA significantly and dose-dependently increased oxidative stress (P<0.001
      0.0001). CONCLUSIONS: Supplementation with FO for prior to and during pregnancy
      significantly increased LPS-induced inflammation in the amniotic fluid, uterus,
      and placenta and significantly increased maternal systemic oxidative stress in
      vivo. Likewise, DHA and EPA induced oxidative stress in macrophage-like cells in
      vitro.

PMID- 25381940
TI  - The time-associated impact of the Newborn Influenza Protection Act on infant
      influenza rates in New York State.
AB  - BACKGROUND: Influenza presents with increased morbidity and mortality in children
      <=5 months of age. Vaccination of caregivers is indicated, but immunization rates
      are estimated at only 30%. The 2009 New York State Neonatal Influenza Protection
      Act (NIPA) mandated offering of influenza vaccine to caregivers during the post
      partum hospitalization. The purpose of this study was to determine the impact of
      NIPA on infant influenza rates. METHOD: Data on laboratory-confirmed influenza
      cases between 2006 and 2012 were extracted from the New York State Electronic
      Clinical Laboratory Reporting System (ECLRS). Data on infant cases were
      categorized by age (0-5 months) and location [New York City (NYC), outside NYC]
      based on reporting laboratory site. The total number of influenza cases and the
      percentage of total cases in the infant age group were normalized to the number
      of reporting laboratory sites. The chi2-test was used to compare the proportions
      of cases pre- and post-implementation. Year-to-year trends were assessed by
      linear regression. All tests of significance were two-sided and evaluated at the
      P<0.05 level. RESULTS: During the 6-year study period, 3154 cases of infant
      influenza were detected. In bivariate analysis, 1707 (54.1%) of cases occurred
      prior to NIPA implementation and 1447 (45.9%) of cases occurred after (P<0.001).
      Of the 1422 total infant cases detected in NYC, the percentages of influenza
      cases pre- and post-NIPA were 54.6% (777) and 45.4% (645), respectively
      (P<0.006). Outside NYC, the percentage of infant cases was reduced from 53.7%
      (930/1732) to 46.3% (802/1732, P<0.02). Prior to implementation, there was a year
      to-year increase in the number of infant influenza cases statewide (P<0.04 for
      trend). The ratio of infant influenza cases normalized per ECLRS site in NYC
      increased each year after NIPA passage (P<0.01 for trend). The ratio of infant
      cases outside NYC decreased annually (P<0.05 for trend). No year-to-year trends
      were seen in the percentage of total influenza cases in the infant age group
      compared to total cases across all age groups either within or outside NYC.
      CONCLUSIONS: Comparison of three influenza seasons before and after NIPA suggests
      a total statewide reduction in infant influenza. However, the greatest driver of
      this reduction occurs from reduced disease in infants outside NYC. We speculate
      that, with increased crowding within NYC, parental immunization as encouraged by
      NIPA may not create cocoon immunity.

PMID- 25381941
TI  - Endothelial and metabolic disorders in adolescence: low birth weight is not an
      isolated risk factor.
AB  - BACKGROUND: Low birth weight (LBW) seems to be a determining factor for many
      cardiovascular diseases in adult life. OBJECTIVES: The objectives of this study
      were to investigate the occurrence of metabolic syndrome (MetS) and endothelial
      dysfunction in adolescents with LBW and compare them with subjects with normal
      birth weights (NBW). METHODS: This retrospective cohort study evaluated 172
      adolescents (86 in each group) aged 10-20 years, who were born in a reference
      maternity hospital. The following criteria were adopted: International Diabetes
      Federation parameters for the diagnosis of MetS and flow-mediated brachial artery
      dilatation for endothelial dysfunction. Student's t-test or Mann-Whitney tests
      were used for continuous variables (depending on the normality of distribution
      evaluated by the Shapiro-Wilk test), and the Fisher exact test was used for
      categorical variables. The significance level was determined at 0.05. RESULTS:
      MetS was present in three cases of LBW and in four cases of NBW (p=0.70). The
      number of components of the syndrome was, on average, 0.6 and 0.5 in LBW and NBW,
      respectively (p=0.77). Endothelial dysfunction occurred in 25 (29.1%) cases of
      LBW and in 31 (36.1%) cases of NBW (p=0.33). CONCLUSION: LBW did not represent a
      risk factor in the occurrence of MetS or endothelial dysfunction in adolescence.

PMID- 25381942
TI  - Inhibin B in adolescents and young adults with Turner syndrome.
AB  - OBJECTIVE: Primary gonadal failure may occur in most individuals with Turner
      syndrome (TS). Since ovaries in TS girls undergo premature apoptosis and
      cryopreservation of ovarian tissue is now feasible, it would be useful to
      identify a reliable marker of ovarian reserve in these patients. We planned to
      evaluate ovarian function in a group of TS patients by measuring both traditional
      markers and inhibin B and to compare these results with those of a control group.
      STUDY DESIGN: We enrolled 23 patients with TS and 17 age-matched healthy girls.
      The median age of our TS patients was 17.6 years. Three out of the 23 patients
      (13%) showed spontaneous pubertal development and regular menstrual cycles; the
      remaining 20 (86.9%) presented with primary amenorrhea. RESULTS: The median level
      of inhibin B in the TS patients with primary amenorrhea was 42 pg/mL and did not
      differ significantly among the different subgroups in relation to karyotype. The
      median inhibin B level in the control group was significantly higher than in the
      TS girls with primary amenorrhea (83 vs. 42 pg/mL, p<0.00001). In the three
      patients with TS and spontaneous menstrual cycles, the inhibin B levels were
      significantly higher when compared to the values of the TS girls with primary
      amenorrhea. CONCLUSION: TS patients with primary amenorrhea have significantly
      lower levels of inhibin B than TS girls with spontaneous puberty and healthy
      controls. Inhibin B does not correlate with follicle-stimulating
      hormone/luteinizing hormone. If our results are confirmed in further studies,
      inhibin B could become a first-line screening test for assessing ovarian reserve
      and a longitudinal marker of the possible decline of ovarian function in TS.

PMID- 25381943
TI  - Is there a relationship between cardiovascular risk factors and
      dehydroepiandrosterone sulfate levels in childhood obesity?
AB  - AIM: In this study, parameters of metabolic syndrome and dehydroepiandrosterone
      sulfate (DHEAS) levels in obese children and adolescents were evaluated and the
      associations between these factors were analyzed. METHOD: One hundred obese and
      40 healthy children/adolescents were included in the study. Pubertal stages,
      anthropometric and blood pressure measurements were recorded. Levels of fasting
      serum lipids, glucose, insulin, and DHEAS, and liver function tests were
      determined. Carotid intima-media thickness (CIMT) was measured using two
      dimensional echocardiography. Steatorrhoeic hepatosis was evaluated using
      abdominal ultrasonography in the obese group. RESULTS: Mean body weight, body
      mass index, waist, hip circumference, waist/hip ratio, homeostatic model
      assessment of insulin resistance, triglycerides, high-density lipoprotein
      cholesterol, alanine transferase, DHEAS, and CIMT values were significantly
      higher in the obese group than in the controls. DHEAS levels were found to be
      positively correlated with waist circumference, waist/hip ratio, and CIMT.
      CONCLUSION: Early determination of metabolic and cardiac dysfunction in obese
      children is important for the prevention of future complications. Since in this
      study we found a strong association between DHEAS levels and obesity-related
      metabolic and cardiovascular risk factors, we believe that this may lead to
      increased interest in further studies of DHEAS in the search for new treatment
      approaches.

PMID- 25381944
TI  - Novel mutations in the SLC25A13 gene in a patient with NICCD and severe
      manifestations.
AB  - Neonatal intrahepatic cholestatic due to citrin deficiency (NICCD) is an
      autosomal recessive disorder caused by mutations in the SLC25A13 gene and
      characterized by neonatal/infantile-onset cholestatic hepatitis syndrome
      associated with conjugated hyperbilirubinemia and multiple aminoacidemias. We
      report the case of a Chinese female patient with NICCD disease who manifested
      prominent clinical features. The patient was diagnosed with NICCD based on
      cholestasis, aminoacidemia, and hypoproteinemia. She exhibited extreme
      aminoacidemia, coagulation disorders and untypical myocardial damage, which are
      rare in other NICCD patients genetically confirmed by us. This myocardial damage
      observed in obstructive jaundice could be caused by both hyperbilirubinemia and
      redundant blood bile acids. Screening the SLC25A13 gene revealed that this
      patient was compound heterozygous harboring two novel mutations, the c. 640C>T
      (p. Gln214X) in exon 7 and the c. 1709_1710insA (p. Ile570fs573X) in exon 16.
      Both mutations cause a premature stop codon and thereby truncated peptide or
      nonsense-mediated with loss of natural function accordingly. In conclusion,
      extremely manifested clinical features, including significant hyperbilirubinemia,
      multiple aminoacidemia, hypoproteinemia, coagulation disorders, and myocardial
      damage related to redundant blood bilirubin and bile acids, were observed in a
      NICCD patients with two novel mutations. 

PMID- 25381945
TI  - Mode of initial presentation and chromosomal abnormalities in Irish patients with
      Turner syndrome: a single-centre experience.
AB  - BACKGROUND: Age at diagnosis of girls with Turner syndrome (TS) is an important
      indicator of successful management. We determined the age, initial clinical
      presentation, and chromosomal abnormalities in patients with TS. METHODS: This
      was a retrospective evaluation of the clinical and laboratory records of patients
      with TS. RESULTS: Sixty-five patients with TS were identified; 40 (62%) were
      diagnosed after age 5 years. The main presenting features were short stature,
      delayed puberty, dysmorphic features, and neonatal lymphoedema. Chromosomal
      analysis of this cohort showed that 31 patients demonstrated mosaicism, while a
      45,X karyotype was observed in 19. The remaining patients had variable
      abnormalities including deletion, translocation, isochromosome, and ring
      chromosome. Y-chromosome material was found in four cases. CONCLUSIONS: Most
      patients with TS were diagnosed after age 5 years, had a varied clinical
      presentation, and had a wide range of chromosomal abnormalities.

PMID- 25381946
TI  - An asymptomatic mother diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency
      after newborn screening.
AB  - BACKGROUND: 3-Methylcrotonyl-CoA carboxylase (3-MCC) deficiency is an autosomal
      recessively inherited disease of leucine catabolism. It is the most commonly
      observed organic acidemia where tandem mass spectrometry can be performed in
      newborn screening. The clinical phenotypes may differ from neurological
      involvement in newborns to asymptomatic adults. Diagnosis is made by increased 3
      hydroxyisovaleric acid in blood and 3-methylcrotonylglycine in urine. CASE
      REPORT: We would like to present an interesting case of a 32-year-old
      asymptomatic mother, who was investigated metabolically and diagnosed with 3-MCC
      deficiency, after a 7-day-old healthy baby referred to our unit with the
      preliminary diagnosis of organic academia during her extended newborn screening.
      RESULTS: All of the metabolic findings of the baby were normal except for very
      low carnitine levels. Her mother's total and free carnitine levels were also
      extremely low. Urine organic acid analysis revealed excessively increased 3
      methylcrotonylglycine and 3-hydroxyisovaleric acid. Acylcarnitine profile showed
      markedly elevated C5 hydroxy 3 hydroxyisovalerylcarnitine and decreased C2
      acetylcarnitine. In order to confirm the diagnosis of 3-methylcrotonylglycinuria,
      molecular analysis was done, and IVS3-1G>C/p.T556I compound heterozygote mutation
      was detected. p.T556I is a novel mutation. CONCLUSION: We would like to emphasize
      performing extended metabolic investigations in case of suspicion of metabolic
      disease in order to diagnose metabolic diseases both in babies and in
      asymptomatic mothers.

PMID- 25381947
TI  - Is ultrasound useful in the diagnosis of adolescents with polycystic ovary
      syndrome?
AB  - BACKGROUND: Diagnosis of adolescent polycystic ovary syndrome (PCOS) remains a
      challenge despite several existing criteria, and may be difficult to distinguish
      from pubertal changes. Different parameters to study ovarian function using
      ultrasonography have been proposed, but there is still no consensus about their
      diagnostic value. OBJECTIVE: To evaluate the role of ultrasonography in the
      diagnosis of adolescent PCOS by reviewing available studies that assessed the
      ovarian volume (OV) and other ovarian morphological features such as location and
      number of follicles, stromal area, and volume. METHODS: MEDLINE/PubMed database
      were searched to identify studies that assessed ovarian characteristics of
      adolescent PCOS patients by ultrasound. Studies on adults were also reviewed if
      study population included adolescents and stromal characteristics were assessed
      by three-dimensional (3D) sonogram. RESULTS: Five studies, including 262 PCOS
      adolescents (10-19 years of age) and two-dimensional (2D) ultrasound analysis,
      were identified. Mean OV was 9.29 cm3 for PCOS patients and 4.77 cm3 for
      controls. The morphology of ovarian follicles, when reported, showed multiple
      (>10) peripheral follicles in 83% of cases. Two studies, including 157 PCOS
      adolescents and young women (15-35 years of age) and 2D and 3D ultrasound
      analysis, were identified. Patients with PCOS patients had a MOV 13.1 cm3,
      multiple follicles (>15), and a statistically significant greater S/A ratio
      compared to controls. Stromal volume indices were positively correlated with
      hyperandrogenemia in PCOS patients. CONCLUSION: Pelvic ultrasound is an
      increasingly important aid in the diagnosis of PCOS in adolescents. Besides
      ovarian volume, ovarian morphology must be assessed with 2D ultrasound to look
      for peripherally located multiple follicles. Further studies are warranted to
      evaluate the utility of 3D ultrasonographic assessment in adolescents with PCOS.

PMID- 25381948
TI  - Hypothalamic obesity after treatment for craniopharyngioma: the importance of the
      home environment.
AB  - Hypothalamic obesity after treatment for craniopharyngioma is a well-recognized,
      severe problem. Treatment of hypothalamic obesity is difficult and often
      frustrating for the patient, the parents and the professional care-giver. Because
      hypothalamic obesity is caused by an underlying medical disorder, it is often
      assumed that regular diet and exercise are not beneficial to reduce the
      extraordinarily high body mass index, and in fact, lifestyle interventions have
      been shown to be insufficient in case of extreme hypothalamic obesity.
      Nevertheless, it is important to realize that also in this situation, informal
      care delivered by the family and appropriate parenting styles are required to
      minimize the obesity problem. We present a case in which weight gain in the home
      situation was considered unstoppable, and a very early mortality due to
      complications of the severe increasing obesity was considered inevitable. A
      permissive approach toward food intake became leading with rapid weight increase
      since a restrictive lifestyle was considered a senseless burden for the child. By
      admission to our hospital for a longer period of time, weight reduction was
      realized, and the merely permissive approach could be changed into active
      purposeful care by adequate information, instruction, guidance and encouragement
      of the affected child and her parents. This case illustrates that, although this
      type of obesity has a pathological origin, parental and environmental influences
      remain of extreme importance.

PMID- 25381949
TI  - A new missense mutation in the BCKDHB gene causes the classic form of maple syrup
      urine disease (MSUD).
AB  - Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disease
      caused by mutations in the BCKDHA, BCKDHB, DBT and DLD genes, which encode the
      E1alpha, E1beta, E2 and E3 subunits of the branched chain alpha ketoacid
      dehydrogenase (BCKD) complex, respectively. This complex is involved in the
      metabolism of branched-chain amino acids. In this study, we analyzed the DNA
      sequences of BCKDHA and BCKDHB genes in an infant who suffered from MSUD and died
      at the age of 6 months. We found a new missense mutation in exon 5 of BCKDHB gene
      (c.508C>T). The heterozygosity of the parents for the mentioned nucleotide change
      was confirmed by direct sequence analysis of the corresponding segment. Another
      missense mutation has been found in the same codon previously and shown by in
      silico analyses to be deleterious. This report provides further evidence that
      this amino acid change can cause classic MSUD. 

PMID- 25381950
TI  - Neuroinflammation and demyelination from the point of nitrosative stress as a new
      target for neuroprotection.
AB  - The role of nitrosative stress in the early pathogenesis of neuroinflammation and
      demyelination is undoubtedly wide. This review summarizes and integrates the
      results, found in previously performed studies, which have evaluated nitrosative
      stress participation in neuroinflammation. The largest number of studies
      indicates that the supply of nitrosative stress inhibitors has led to the
      opposite clinical effects in experimental studies. Some results claim that
      attributing the protective role to nitric oxide, outside the total changes of
      redox oxidative processes and without following the clinical and paraclinical
      correlates of neuroinflammation, is an overrated role of this mediator. The fact
      is that the use of nitrosative stress inhibitors would be justified in the
      earlier phases of neuroinflammation. The ideal choice would be a specific
      inducible nitric oxide synthase (iNOS) inhibitor, because its use would preserve
      the physiological features of nitric oxide produced by the effects of
      constitutive NOS. This review discusses the antinitrosative therapy as a
      potential mode of therapy that aims to control neuroinflammation in early phases,
      delaying its later phases, which are accompanied with irreversible neurological
      disabilities. Some parameters of nitrosative stress might serve as surrogate
      biomarkers for neuroinflammation intensity and its radiological and clinical
      correlates.

PMID- 25381951
TI  - Geraniol attenuates oxidative stress by Nrf2 activation in diet-induced
      experimental atherosclerosis.
AB  - BACKGROUND: Preclinical and clinical studies suggest the use of antioxidants as
      an effective measure to reduce the progression of oxidative-stress-related
      disorders. Nuclear factor E2-related factor 2 (Nrf2) is a key component to
      cellular redox homeostasis in the attenuation of oxidative-stress-associated
      pathological processes. The objective of the current study was to evaluate the
      role of geraniol (GOH) in preserving the plasma lipid status, endothelial
      function, antioxidant status, and inhibition of lipid peroxidation (LPO) in
      hamsters fed an atherogenic diet (AD). METHODS: Male Syrian hamsters were
      randomly grouped into four groups: group 1 was control animals; group 2 was
      animals fed GOH alone (100 mg/kg bw po); group 3 was animals fed AD (standard
      pellet diet+10% coconut oil+0.25% cholesterol+0.25% cholic acid); and group 4 was
      fed AD+GOH (100 mg/kg bw) for 12 weeks. At the end of the feeding period, the
      animals were sacrificed and the liver, heart, and aorta from each group were
      analyzed for antioxidants, LPO markers, and histological changes. RESULTS: AD
      feeding induced a significant change in lipid profile, endothelial function
      marker, activities of the antioxidant enzymes, alterations in the LPO markers,
      Nrf2 expression, and equally significant changes in the organ histology.
      CONCLUSIONS: Supplementation with GOH appreciably prevented the alterations
      induced by the AD on all the above parameters. Thus, GOH offers marked protection
      against AD-induced abnormalities.

PMID- 25381952
TI  - The role of serpins in tumor cell migration.
AB  - Tumor cells are characterized by uncontrolled cell growth at a primary site that
      is caused by genetic alterations. Tumor cells that metastasize from their primary
      site to distant locations are commonly referred to as malignant. Cell migration
      is a critical step in this process. The ability of tumor cells to migrate and
      invade is partly controlled by proteolytic enzymes. These enzymes are secreted by
      either the tumor cells themselves or adjacent cells. They represent all classes
      of proteases, including serine and cysteine proteases. Serine proteases, in
      particular urokinase plasminogen activator (uPA), initiate a proteolytic cascade
      that culminates in degrading components of the extracellular matrix (ECM). Some
      serine proteases are controlled by a superfamily of proteins known as serpins.
      This minireview provides an overview of serpins that are vital in regulating
      tumor cell migration and progressing cancer.

PMID- 25381953
TI  - Kinetics of high-sensitivity cardiac troponin T or troponin I compared to
      creatine kinase in patients with revascularized acute myocardial infarction.
AB  - BACKGROUND: Cardiac biomarkers are the cornerstone of the biological definition
      of acute myocardial infarction (AMI). The key role of troponins in diagnosis of
      AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine
      kinase (CK) after AMI are correlated to the prognosis. New technical assessment
      like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its
      unclear kinetic following the peak. This study aims to compare kinetics of cTnI
      and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous
      coronary intervention (PCI). METHODS: We prospectively studied 62 patients with
      anterior AMI successfully reperfused with primary angioplasty. We evaluated two
      consecutive groups: the first one regularly assessed by both CK and cTnI methods
      and the second group by CK and hs-cTnT. Modeling of kinetics was realized using
      mixed effects with cubic splines. RESULTS: Kinetics of markers showed a peak at
      7.9 h for CK, at 10.9 h (6.9-12.75) for cTnI and at 12 h for hs-cTnT. This peak
      was followed by a nearly log linear decrease for cTnI and CK by contrast to hs
      cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h.
      There was no significant difference between the decrease of cTnI and CK (p=0.63).
      CK fell by 79.5% (76.1-99.9) vs. cTnI by 86.8% (76.6-92.7). In the hs-cTnT group
      there was a significant difference in the decrease by 26.5% (9-42.9) when
      compared with CK that fell by 79.5% (64.3-90.7). CONCLUSIONS: Kinetic of hs-cTnT
      and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be
      investigated.

PMID- 25381954
TI  - Exploration of the pre-analytical stability of beta-lactam antibiotics in plasma
      and blood--implications for therapeutic drug monitoring and pharmacokinetic
      studies.

PMID- 25381955
TI  - Different methods to estimate serum free cortisol: a comparison during cortisol
      tetracosactide testing.
AB  - BACKGROUND: Serum cortisol is routinely quantified by immunoassays. In intensive
      care units serum free cortisol (FC) determination has been described as a better
      indicator of survival than total cortisol (TC). To estimate FC different methods
      are available including saliva sampling. We compared five methods to estimate FC,
      before and after an ACTH stimulating test in patients suspected of adrenal
      insufficiency. METHOD: Serum and saliva was collected from 130 patients from the
      Endocrine Department of a university hospital before and after tetracosactide
      injection for TC determination. FC was estimated: after serum ultrafiltration,
      quadratic (Coolens') or cubic (Dorin's) equations, using TC/cortisol-binding
      globulin concentrations ratio or using cortisol concentration determination in
      saliva. RESULTS: FC concentrations obtained by different techniques were
      significantly correlated and Passing-Bablok regressions showed no deviation from
      linearity between salFC and filtFC or quadFC. Using the routine assumption that
      the patients were correctly diagnosed using a post-tetracosactide TC threshold of
      550 nmol/L the FC methods generating the best ROC curves were salFC and filtFC or
      cubFC 30 min after tetracosactide injection. CONCLUSIONS: FC concentrations
      obtained by different techniques are significantly but not similarly correlated
      with TC. As, salFC and filtFC are more convenient to perform than methods
      involving CBG assays and are better correlated to TC during tetracosactide tests
      they may be preferred as FC surrogate assays.

PMID- 25381956
TI  - The new and the old of heparin-induced thrombocytopenia.

PMID- 25381957
TI  - Broadband metallic absorber on a non-planar substrate.
AB  - Absorbers for visible and near-infrared light are realized by depositing a thin
      iron layer on arrays of cones which are replicated from a porous template. The
      replicated conic structure itself is of several micrometers and ineffective at
      antireflection, but the subsequent deposition of iron on top generates nano-meter
      size columnar structures, and thus broadband absorption enhancement is achieved. 

PMID- 25381959
TI  - A multidisciplinary conceptualization of conservation opportunity.
AB  - An opportunity represents an advantageous combination of circumstances that
      allows goals to be achieved. We reviewed the nature of opportunity and how it
      manifests in different subsystems (e.g., biophysical, social, political,
      economic) as conceptualized in other bodies of literature, including behavior,
      adoption, entrepreneur, public policy, and resilience literature. We then
      developed a multidisciplinary conceptualization of conservation opportunity. We
      identified 3 types of conservation opportunity: potential, actors remove barriers
      to problem solving by identifying the capabilities within the system that can be
      manipulated to create support for conservation action; traction, actors identify
      windows of opportunity that arise from exogenous shocks, events, or changes that
      remove barriers to solving problems; and existing, everything is in place for
      conservation action (i.e., no barriers exist) and an actor takes advantage of the
      existing circumstances to solve problems. Different leverage points characterize
      each type of opportunity. Thus, unique stages of opportunity identification or
      creation and exploitation exist: characterizing the system and defining problems;
      identifying potential solutions; assessing the feasibility of solutions;
      identifying or creating opportunities; and taking advantage of opportunities.
      These stages can be undertaken independently or as part of a situational analysis
      and typically comprise the first stage, but they can also be conducted
      iteratively throughout a conservation planning process. Four types of
      entrepreneur can be identified (business, policy, social, and conservation), each
      possessing attributes that enable them to identify or create opportunities and
      take advantage of them. We examined how different types of conservation
      opportunity manifest in a social-ecological system (the Great Barrier Reef) and
      how they can be taken advantage of. Our multidisciplinary conceptualization of
      conservation opportunity strengthens and legitimizes the concept. 

PMID- 25381958
TI  - Influence of bony resection margins and surgicopathological factors on outcomes
      in limb-sparing surgery for extremity osteosarcoma.
AB  - BACKGROUND: Limb-sparing surgery for osteosarcoma requires taking wide bony
      resection margins while maximizing preservation of native bone and joint.
      However, the optimal bony margin and factors associated with recurrence and
      survival outcomes in these patients are not well established. PROCEDURE: We
      conducted a retrospective review of outcomes in children and adolescents with
      newly diagnosed osteosarcoma from 1986 to 2012, where bony resection margins for
      limb-sparing surgeries were decreased serially from 5 to 1.5 cm. The association
      between bony margins and other surgicopathological factors with survival and
      recurrence outcomes was determined. RESULTS: In 181 limb-sparing surgeries in 173
      patients, planned and actual bony resection margins were not significantly
      associated with local recurrence-free survival (LRFS), event-free survival (EFS),
      and overall survival (OS)-at median 5.8 years follow-up, decreasing planned bony
      resection margins from 5 to 1.5 cm did not significantly decrease survival
      outcomes. Multivariable analysis showed that the presence of distant metastases
      at diagnosis was associated with decreased LRFS, EFS, and OS (P = 0.002, 0.005,
      and <0.0001, respectively). Post-chemotherapy tumor necrosis <=90% was associated
      with decreased EFS and OS (P = 0.001 and 0.022, respectively). Earlier years of
      treatment and pathologic fractures were associated with decreased OS only (P =
      0.018 and 0.008, respectively); previous cancer history and male gender were
      associated with decreased EFS only (P = 0.043 and 0.023, respectively).
      CONCLUSION: We did not observe significant increase in adverse survival outcomes
      with reduction of longitudinal bony resection margins to 1.5 cm. Established
      prognostic factors, particularly histologic response to chemotherapy and
      metastases at diagnosis, remain relevant in limb-sparing patients. Pediatr Blood
      Cancer 2015;62:246-251. (c) 2014 Wiley Periodicals, Inc.

PMID- 25381960
TI  - Synthesis and characterization of a library of in-situ curing, nonswelling
      ethoxylated polyol thiol-ene hydrogels for tailorable macromolecule delivery.
AB  - A transesterfication reaction is used to synthesize tri-thiol-functionalized
      ethoxylated polyols that are combined with polyethylene glycol diacrylates to
      form a biodegradable hydrogel library. Hydrogels display nonswelling
      equilibration and offer temporal control over material degradation and the
      release of biomolecules. The demonstrated in vitro biocompatibility makes this a
      versatile platform that can be used for local drug delivery to volume-constrained
      anatomical sites. 

PMID- 25381961
TI  - Conversion between mini-mental state examination, montreal cognitive assessment,
      and dementia rating scale-2 scores in Parkinson's disease.
AB  - Cognitive impairment is one of the earliest, most common, and most disabling non
      motor symptoms in Parkinson's disease (PD). Thus, routine screening of global
      cognitive abilities is important for the optimal management of PD patients. Few
      global cognitive screening instruments have been developed for or validated in PD
      patients. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment
      (MoCA), and Dementia Rating Scale-2 (DRS-2) have been used extensively for
      cognitive screening in both clinical and research settings. Determining how to
      convert the scores between instruments would facilitate the longitudinal
      assessment of cognition in clinical settings and the comparison and synthesis of
      cognitive data in multicenter and longitudinal cohort studies. The primary aim of
      this study was to apply a simple and reliable algorithm for the conversion of
      MoCA to MMSE scores in PD patients. A secondary aim was to apply this algorithm
      for the conversion of DRS-2 to both MMSE and MoCA scores. The cognitive
      performance of a convenience sample of 360 patients with idiopathic PD was
      assessed by at least two of these cognitive screening instruments. We then
      developed conversion scores between the MMSE, MoCA, and DRS-2 using
      equipercentile equating and log-linear smoothing. The conversion score tables
      reported here enable direct and easy comparison of three routinely used cognitive
      screening assessments in PD patients.

PMID- 25381962
TI  - Abciximab-induced alveolar hemorrhage treated with rescue extracorporeal
      membranous oxygenation.
AB  - We describe a case of a 75-year-old woman presenting emergently with an anterior
      S-T elevation myocardial infarction that deteriorated into ventricular
      fibrillation requiring prompt resuscitation, resulting in cardiogenic shock.
      Emergency primary percutaneous coronary intervention of the left anterior
      descending coronary artery with adjunctive abciximab and heparin resulted in
      adequate coronary flow, and intra-aortic balloon pump was used to support
      hemodynamics. Within one hour of intervention, she developed acute respiratory
      distress with four-quadrant opacification of lung fields, difficulty with
      oxygenation, and hypotension. Emergency bronchoscopy revealed diffuse
      erythematous proximal airways with bloody secretions bilaterally confirming
      diffuse alveolar hemorrhage. An emergency veno-arterial extracorporeal membranous
      oxygenation (ECMO) circuit was placed at the bedside, acutely improving
      oxygenation and hemodynamics. She survived the hospitalization with multiple
      complications related to access site and prolonged intensive care unit stay, was
      discharged to acute rehabilitation. She is currently thriving 18 months post
      procedure. This case highlights the use of ECMO in the often-fatal condition of
      diffuse alveolar hemorrhage related to glycoprotein inhibitor use.

PMID- 25381964
TI  - Does exposure to hyperglycaemia in utero increase the risk of obesity and
      diabetes in the offspring? A critical reappraisal.
AB  - BACKGROUND: The idea that exposure to hyperglycaemia in utero is an important
      factor in the development of obesity and diabetes in the offspring has become
      entrenched as popular belief. AIM: To appraise the literature supporting this
      hypothesis in the light of recent studies that have clarified the main drivers of
      obesity in children and adolescents. METHODS: A review of published evidence from
      animal studies, human observational studies, systematic reviews and experimental
      trials that address the impact of diabetes (Types 1 and 2, genetic or
      gestational) on the future risk of obesity and/or glucose intolerance in the
      offspring. RESULTS: Some animal studies support a relationship between exposure
      to hyperglycaemia in utero and future development of obesity and diabetes, but
      the results are inconsistent. Most of the human studies claiming to show a
      relationship have not taken into account important known confounders, such as
      maternal and paternal BMI. Evidence supporting a dose-response relationship
      between maternal hyperglycaemia exposure and obesity and diabetes in the
      offspring is weak, and there is no convincing evidence that treating gestational
      diabetes reduces the later risk of offspring obesity or glucose intolerance.
      CONCLUSIONS: Exposure to hyperglycaemia in utero has minimal direct effect on the
      later risk of obesity and Type 2 diabetes. The increased risk of obesity in the
      offspring of women with Type 2 or gestational diabetes can be explained by
      confounding factors, such as parental obesity.

PMID- 25381965
TI  - Seminars in research 2013: joint experiences using biologics in rheumatology and
      dermatology.

PMID- 25381966
TI  - Detection of adalimumab and anti-adalimumab levels by ELISA: clinical
      considerations.
AB  - Psoriasis (Ps) is a common and stigmatizing chronic inflammatory skin disease
      that may cause other chronic inflammatory conditions with overlapping pathology,
      such as rheumatoid arthritis (RA). Tumor necrosis factor (TNF) is a
      proinflammatory cytokine that plays a pivotal role in chronic inflammatory and
      autoimmune diseases such as uveitis, multiple sclerosis, systemic lupus,
      arthritis, Ps, and Crohn's disease. The TNF superfamily and receptors represent
      active targets for drug development. Anti-TNF biological therapies, such as
      infliximab, adalimumab (ADL), and etanercept, are effective in treating RA,
      spondyloarthritis, Ps, and inflammatory bowel diseases, but long-term treatment
      can induce anti-drug antibody (ADA) formation associated with lower drug levels
      and clinical nonresponse. An investigation of the relationship between serum
      ADL/anti-adalimumab antibody (AAA) concentration, and clinical response in
      moderate to severe Ps, confirmed an association between ADL and AAA levels and
      response. Although the detection of ADAs can be used to determine the cause of
      nonresponse and aid therapy decisions, the contrary observation of long-term
      responders with low drug levels and detectable ADA suggests that another
      mechanism is also involved.

PMID- 25381967
TI  - Killer-cell immunoglobulin-like receptors (KIR) and HLA-class I heavy chains in
      ankylosing spondylitis.
AB  - HLA-B27 (B27) interactions with the killer-cell immunoglobulin-like receptors
      (KIR) have been implicated in the pathogenesis of ankylosing spondylitis (AS),
      with consistent differences among populations. KIR3DL1 and possibly KIR3DS1
      interact with classical B27, whereas KIR3DL2 binds B27 heavy chain dimers. The
      aim of this review is to summarize data from recent studies performed in our
      laboratory and from the literature, which provide support for a possible role of
      KIR3DL2/B27 dimer interactions in the pathogenesis of AS. Recent studies in cells
      from AS patients and from health controls carrying the predisposing B*2705 and
      the nonpredisposing B*2709 haplotypes, have shown a higher percentage of positive
      cells and a higher surface expression of KIR3DL2 receptors on natural killer (NK)
      and CD4+ T cells in B*2705 AS patients compared with B*2705, B*2709 and B27
      negative healthy controls. Increased expression of HC10-reactive molecules on AS
      monocytes was seen, supporting the possible role of the KIR3DL2/B272 pair in the
      pathogenesis of AS. These results underline the importance of NK cells and innate
      immunity, and of CD4+ T cells in the inflammatory pathogenesis of AS.

PMID- 25381968
TI  - Thalassemic trait prevalence in patients affected by psoriatic arthritis in anti
      TNF treatment.
AB  - Thalassemic trait (Thal) is associated with rheumatic disease, particularly a
      mild form of seronegative polyarthritis resembling rheumatoid arthritis (RA), but
      not with other rheumatic diseases. The aim of this study was to estimate the
      frequency of Thal in patients with psoriatic arthritis (PsA) and to evaluate the
      efficacy of anti-tumor necrosis factor alpha (TNF-alpha) therapy in patients with
      PsA and Thal. We performed a retrospective study in 321 patients with PsA who
      started therapy with TNF-alpha blockers. For all patients included in the study,
      at baseline and every 3 months for the 1 year of follow up, data concerning PsA
      activity and ferritin levels were registered. In our group of PsA patients, a
      total of 27 (8%) with concomitant Thal were identified and included in the study.
      In patients without Thal, all variables improved significantly after 6 months of
      therapy, while in patients with Thal, the same variables showed a significant
      decrease after 12 months.: Our study shows that PsA is significantly associated
      with Thal, but further studies are needed to address this issue. The presence of
      Thal could be a negative predictor of achieving remission during treatment with
      TNF-alpha-blockers.

PMID- 25381969
TI  - Management of patients with psoriasis treated with biological drugs needing a
      surgical treatment.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a cytokine that plays a critical role
      in inflammatory and immune processes and in the control of infections and sepsis.
      Data on the perioperative management of patients treated with biologic drugs are
      limited and mainly in patients with rheumatoid arthritis (RA) and inflammatory
      bowel disease (IBD). This retrospective study assesses variations in the
      incidence of side effects between psoriatic patients who temporarily discontinue
      or continue biological therapy before surgical treatment. Despite the
      immunosuppressive risk, our results suggest that postoperative complications are
      not influenced by the suspension of biologic therapies. As TNF-alpha plays a role
      in promoting collagen synthesis and wound healing, we suggest that anti-TNFs
      should be discontinued before major surgery, whereas for minor surgery, the lower
      rates of infections favor anti-TNF-alpha continuation, particularly since
      suspending anti-TNF therapy is known to induce psoriasis relapse.

PMID- 25381970
TI  - Clinical markers predictive of primary inefficacy: a "real life" retrospective
      study in psoriatic patients treated with etanercept.
AB  - Overexpression of tumor necrosis factor alpha (TNF-alpha) has been demonstrated
      to play a pivotal role in the pathogenesis of both plaque-type psoriasis and
      psoriatic arthritis. TNF-alpha blockers, including etanercept, a human protein
      that acts as a TNF-alpha soluble receptor, are effective in the treatment of
      psoriasis. This retrospective study investigated the impact of psoriasis
      patients' demographic and clinical characteristics on primary inefficacy to
      etanercept. Our findings suggest that the presence of psoriatic arthritis is a
      risk factor for primary inefficacy to etanercept in the treatment of psoriasis.
      However, etanercept efficacy appears to be independent of patient age, gender, or
      previous biologic treatments.

PMID- 25381971
TI  - Treatment adherence to different etanercept regimens, continuous vs.
      intermittent, in patients affected by plaque-type psoriasis.
AB  - Treatment adherence to anti-tumor necrosis factor alpha (anti-TNF-alpha) agents
      is marker of treatment success, but overall efficacy of anti-TNF-alpha therapy
      decreases over time leading to a progressive loss of adherence. The present
      observational study was conducted in order to estimate the long-term adherence to
      etanercept in patients affected by plaque-type psoriasis, evaluating differences
      among intermittent and continuous treatment regimen. Our findings reflect routine
      clinical practice in three academic referral centers and show high treatment
      adherence with etanercept in psoriatic patients. Treatment survival was
      consistently high in the short/medium term. The univariate analysis showed longer
      treatment duration in patients undergoing intermittent treatment regimen (mean
      1,706 days) compared with continuous regimen (mean 1,249 days). Results showed
      that a flexible pulsed treatment with etanercept can be optimal in terms of
      clinical success and adherence.

PMID- 25381972
TI  - Monoclonal gammopathy of undetermined significance in patients with psoriasis: is
      it really a side effect of biological therapy?
AB  - Moderate-to-severe psoriasis is treated using biological drugs targeting
      cytokines involved in the pathogenesis of the disease, such as tumor necrosis
      factor alpha (TNF-alpha) (adalimumab, infliximab, etanercept) and interleukin
      12/23 (IL 12/23) (ustekinumab). There is a slight risk of developing
      hematological malignancies, such as monoclonal gammopathy of undetermined
      significance (MGUS) with anti TNF-alpha agents. There are no data available on
      anti-IL12/23 drugs. This retrospective study of data from 191 patients describes
      the appearance and follow-up of MGUS in three patients with psoriasis receiving
      long-term biological therapy. Since the appearance of MGUS occurred after about 6
      years of anti-TNFalpha treatment in only three subjects, it was deemed unlikely
      to be due to the biological treatment. The decision not to suspend biological
      therapy after the appearance of MGUS was taken after careful assessment of the
      possible risks and benefits.

PMID- 25381973
TI  - Ten-year drug survival of anti-TNF agents in the treatment of inflammatory
      arthritides.
AB  - Tumor necrosis factor (TNF) inhibitor therapies (anti-TNFs) are used routinely as
      first-line biotherapy for the treatment of rheumatoid arthritis (RA) and
      spondyloarthritis (SpA: psoriatic arthritis [PsA] and ankylosing spondylitis
      [AS]) in patients who have failed traditional non-biologic disease-modifying anti
      rheumatic drugs (DMARDs). However, about 30% of patients experience failure of
      first-line anti-TNF agent because of inefficacy or adverse events. This study
      analyzed long-term anti-TNFalpha drug survival in a clinical practice setting.
      The overall 10-year retention rate of first-line anti-TNF agent is about 23%,
      being significantly higher for SpA compared with RA patients. ETN is the most
      persistent anti-TNF with a drug survival rate significantly higher than IFX and
      ADA.

PMID- 25381974
TI  - Assays and strategies for immunogenicity assessment of biological agents.
AB  - Some patients with chronic inflammatory diseases either do not respond to or lose
      their initial responsiveness to Tumor Necrosis Factor (TNF) inhibitor therapy. In
      these patients, the clinical response after switching to another anti-TNF drug
      suggests that lack of response is not related to the therapeutic target itself
      but immunogenicity. All biologics are potentially immunogenic and can induce the
      development of antidrug antibodies (ADAs). ADA formation is associated with lower
      serum drug levels, infusion reactions, and loss of response. Analytical methods
      for ADA detection include enzyme-linked immunosorbent assay (ELISA),
      radioimmunoassay (RIA), surface plasmon resonance, and electrochemiluminescence.
      Currently, RIA and ELISA are the preferred methods due to a combination of
      reproducibility, sensitivity, and cost but have some limitations. There is no
      single available assay that has all pros and no cons, and therefore the use of
      more methods for the assessment of samples is a high priority.

PMID- 25381975
TI  - Use of anti-tumor necrosis factor alpha therapy in patients with concurrent
      rheumatoid arthritis and hepatitis B or hepatitis C: a retrospective analysis of
      32 patients.
AB  - The safety of tumor necrosis factor-alpha (TNF-alpha) inhibitors in the setting
      of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is
      controversial. The use of anti-TNF-alpha in rheumatoid arthritis (RA) is
      associated with an increased risk of hepatitis re-activation. This paper reports
      experience of using etanercept and adalimumab in 32 patients with RA and previous
      HBV or HCV infection. No cases of HBV or HCV reactivation were seen. In just over
      a fifth of patients, increased transaminases levels were seen, which were
      associated with concomitant use of disease-modifying antirheumatic drugs,
      isoniazid prophylaxis, or alcohol abuse. In our experience, anti-TNF-alpha
      therapy appears to be safe in RA patients with previous HBV or HCV infection, but
      monitoring remains necessary in these patients.

PMID- 25381976
TI  - Periodontal disease: an oral manifestation of psoriasis or an occasional finding?
AB  - Even if the existence of oral psoriasis has been suggested, it is still a debated
      issue. Indeed, oral inflammatory diseases may histologically resemble psoriasis
      related oral lesions. However, an increased prevalence of fissured tongue and
      geographic tongue has been associated with psoriatic patients, being a transitory
      and permanent lesion, respectively. Recently, it was hypothesized that gingivitis
      and periodontitis share the same underlying inflammatory pathogenetic process of
      psoriasis. Thus, in the present study, psoriatic patients were investigated for
      oral mucosa lesions prevalence as well as gum disease. Results displayed an
      increased association between gingivitis/periodontitis and psoriasis, which may
      suggest common underlying pathogenic risk factors. However, large-scale studies
      are needed to evaluate the real prevalence of gingivitis and periodontitis in
      these patients, to consider them a comorbidity of psoriasis.

PMID- 25381977
TI  - The use of an interferon-gamma release assay as a biomarker of response to anti
      TNF-alpha treatment.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine that plays a
      central role in the immune system functioning and in the pathogenesis of
      rheumatoid arthritis (RA). TNF-alpha inhibition has been demonstrated effective
      to treat RA; however, response to anti-TNF-alpha therapies is heterogeneous, with
      roughly one-third of patients not achieving disease control. Identification of a
      biological marker to assess the effectiveness of TNF-alpha inhibition may help to
      discriminate patients with a reduced response to anti-TNF-alpha agents. The aim
      of this study was to assess whether anti-TNF-alpha treatment was able to modify
      the cytokine network interfering with interferon gamma (INFgamma) release after
      phytohemagglutinin (PHA) stimulation of peripheral blood mononuclear cells
      (PBMCs) from RA patients, according to disease activity. We found that RA
      patients with active disease had low release of INFgamma after PHA stimulation,
      but anti-TNF-alpha agents were able to modify INFgamma production. In anti-TNF
      alpha responders, we observed a higher release of INFgamma, achieving levels
      comparable with those seen in healthy subjects. The ability of PBMCs from RA
      patients to release INFgamma may serve as a biomarker of disease activity and
      response to anti-TNF-alpha. Larger studies are needed to validate these data.

PMID- 25381978
TI  - Insights on the role of physical activity in patients with rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) are physically inactive, and trials have
      been undertaken to examine the effect of physical activity on pain, disease
      activity, functional ability and quality of life (QoL) in RA. The aim of this
      study was to explore the relationship between physical activity and disease
      activity in RA and in healthy controls. Our findings showed that fewer RA
      patients had a professional occupation compared with controls, but patients and
      controls were similar with respect to the sedentary extent of their job. Physical
      exercise was inversely associated with disease activity (DAS-28), stiffness
      visual analog scale (VAS), patient global VAS and SF-36, but not associated with
      Health Assessment Questionnaire (HAQ), pain VAS, fatigue VAS, global health and
      the Arthritis Ipact Measurement Scale (AIMS), suggesting that pain and fatigue
      are important barriers to physical activity. Our findings suggest that this is
      more pronounced in RA patients who do not participate in regular physical
      activity, and so physical exercise should be recommended as part of comprehensive
      RA care.

PMID- 25381979
TI  - Self-reported adherence to a home-based exercise program among patients affected
      by psoriatic arthritis with minimal disease activity.
AB  - More than half of all patients with psoriatic arthritis (PsA) exhibit progressive
      erosive arthritis, associated with severe functional impairment and psychosocial
      disability. Biologics have been suggested to be more effective in inducing
      minimal disease activity" (MDA) than disease-modifying antirheumatic drugs
      (DMARDs). Behavioral patient education appears to be more effective in
      encouraging patients to increase their physical activity (PA) levels. The aim of
      the study was to evaluate the benefits of home-based exercises program on disease
      activity and quality of life in MDA-PsA patients treated with an anti-tumor
      necrosis factor (TNF) and DMARD therapy. We observed a self-reported adherence
      rate to home-based exercise of 76.6% and data showed the impact of the exercise
      program on self-reported health and mental assessment. A positive relationship
      between patient and therapist is crucial, influencing the quality of the
      performance, the emotional support, and increasing motivation in PsA patients.

PMID- 25381980
TI  - Emergence of antinuclear antibodies in psoriatic patients treated with
      infliximab: personal experience and literature review.
AB  - Psoriasis is a chronic inflammatory skin disease affecting up to 2.5% of the
      population, with joint involvement in approximately 30% of patients. Given the
      role of tumor necrosis factor (TNF) in the pathogenesis of psoriasis, anti-TNF
      therapies have been developed; several studies have demonstrated the efficacy of
      infliximab (IFX) as induction and maintenance therapy in the treatment of
      moderate to severe plaque psoriasis. The development of antinuclear antibodies
      (ANA) in anti-TNF-treated patients has been frequently reported. The aim of this
      study was to investigate the incidence of ANA and anti-double stranded DNA (anti
      dsDNA) antibodies in psoriatic patients receiving IFX. Incidence of new ANA and
      anti-ds-DNA was 16.2% and 8.1% respectively. No case of anti-TNF induced Lupus
      was observed during the follow-up.

PMID- 25381981
TI  - A possible role of polycystic ovary syndrome for pregnancy complications in women
      with psoriasis.
AB  - Psoriasis is a common, chronic, relapsing immune-mediated inflammatory disease
      (IMID) of the skin. IMIDs are multifactorial diseases characterized by common
      molecular pathways leading to a systemic inflammation. Patients with an IMID are
      also at higher risk of developing co-morbidities, such as adverse pregnancy
      outcomes, than the general population. A higher rate of pregnancy complications
      have been seen in inflammatory bowel disease and rheumatoid arthritis. The data
      for psoriasis are inconsistent but it appears that women with moderate-to-severe
      psoriasis may also have an increased risk of poor pregnancy outcomes. The cause
      of this association is unknown, although it may be related to elevated
      proinflammatory cytokines such as IL-6 and TNF-alpha, the high prevalence of
      comorbidities and other unhealthy behaviours, or the high prevalence of
      polycystic ovary syndrome (PCOS). In a recent study, PCOS prevalence in a
      psoriatic cohort (n = 51) was higher than in non-psoriatic women (n = 102) (47%
      versus 11%), and women with PCOS and psoriasis had a greater probability of
      insulin resistance, hyperinsulinaemia, and dyslipidaemia as well as a more severe
      skin condition, than those with psoriasis alone. Further studies are necessary to
      clarify the impact of psoriasis on pregnancy and in particular if these effects
      are mediated by concomitant PCOS.

PMID- 25381982
TI  - Decrease of asymmetric dimethyl arginine after anti-TNF therapy in patients with
      rheumatoid arthritis.
AB  - Chronic inflammatory diseases such as rheumatoid arthritis (RA) are associated
      with accelerated atherosclerosis and increased morbidity and mortality for
      cardiovascular events. Asymmetric dimethyl arginine (ADMA), an endogenous
      inhibitor of nitric oxide synthase, contributes to the impairment of endothelial
      function, the earlier and reversible stage of atherosclerotic plaque formation.
      Since tumor necrosis factor (TNF) inhibits enzymatic degradation of ADMA, anti
      TNF agents could restore its physiological level. The aim of this study was to
      investigate the effect of TNF inhibitors on ADMA serum levels in patients with
      RA. Our results suggest a possible effect of anti-TNF drugs on ADMA serum levels;
      longer studies would be necessary to confirm the role ADMA in assessing
      cardiovascular risk in RA.

PMID- 25381983
TI  - Pharmacogenetics and future therapeutic scenarios: what affects the prediction of
      response to treatment with etanercept?
AB  - There are five tumor necrosis factor alpha (TNF-alpha) inhibitors available for
      clinical use that have demonstrated efficacy as monotherapy or in combination
      with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs)
      in the treatment of immune-mediated diseases. These include the anti-TNF-alpha
      monoclonal antibodies infliximab, adalimumab, golimumab, and certolizumab pegol,
      and the fusion protein, etanercept. The use of pharmacogenetic testing has the
      potential to increase drug efficiency by identifying genetic factors responsible
      for a lack of response to, or toxicities from, TNF-alpha inhibitors, and could be
      used to individualize therapy. Several studies have reported associations between
      genetic polymorphisms and the response to etanercept, but most are small and
      insufficiently powered to detect effect, and markers tend to be more prognostic
      than predictive of therapeutic response. Limitations of pharmacogenetic studies
      include the use of single nucleotide polymorphisms (SNPs), genes in linkage with
      other loci, interaction of environmental factors, and cohort heterogeneity, all
      of which can complicate the relationship between genetic polymorphisms and
      treatment response. Further studies are needed for pharmacogenetics to become a
      routine part of daily clinical therapeutic practice.

PMID- 25381984
TI  - Hyperuricemia in patients with chronic plaque psoriasis.
AB  - Psoriasis is frequently associated with obesity, which may favor the development
      of hyperuricemia. Hyperuricemia predisposes patients to gout arthritis and is an
      emerging cardiovascular risk factor. In this study, we investigated the
      prevalence of hyperuricemia and serum uric acid (SUA) levels in psoriatic
      patients. SUA was measured in consecutive psoriatic patients (n = 338) and
      prevalence of hyperuricemia was estimated. Hyperuricemia was defined as SUA >=7
      mg/dL in men and >=6 mg/dL in women. Hyperuricemia affected 20% (67 out 338) of
      patients with psoriasis. SUA levels were 5.8 +/- 1.6 (mean +/- SD) in patients
      with psoriasis. Levels of SUA were significantly higher in obese patients
      compared to non-obese patients (6.1 +/- 1.5 vs 5.2 +/- 1.4, P < 0.05). Levels of
      SUA showed a significant, positive correlation with body mass index (r = 0.30; P
      < 0.01) and serum triglycerides (r = 0.31; P < 0.01) but they were not
      significantly associated with age, sex, psoriasis duration or Psoriasis Area
      Severity Index score. Hyperuricemia is a common finding in psoriatic patients.
      Dosing levels of SUA could be appropriate in the global management of patients
      with psoriasis, particularly in those who are obese and with serum triglycerides
      upper the normal range.

PMID- 25381985
TI  - Effects of TNF-alpha inhibitors on circulating Th17 cells in patients affected by
      severe psoriasis.
AB  - Psoriasis was previously considered to be mostly a Th1 cell-related disorder, but
      Th17 cell has recently emerged as an important player in the pathogenesis of
      psoriasis. The Th17 immune pathway is increased in psoriatic patients, both in
      peripheral circulation and in skin lesions, and positively correlates with the
      Psoriasis Area and Severity Index. Anti-tumor necrosis factor alpha (TNF-alpha)
      agents, in addition to potent inhibition of TNF-alpha activity, are able to
      decrease IL-17 levels and Th17 cells in the skin and plasma of patients with
      moderate-to-severe psoriasis. We found a decrease in the median Th17 cell count
      in peripheral blood after 4 months' therapy with anti-TNF-alpha compared with
      baseline values, but the difference did not reach statistical significance,
      probably due to the small cohort size. Our data suggest that anti-TNF-alpha
      treatment for psoriasis is able to achieve a substantial Th17 cell count
      reduction in the peripheral blood of patients and that this decrease is
      significantly associated with an adequate response to biologic therapy, as
      previous studies in rheumatoid arthritis have shown.

PMID- 25381987
TI  - Cardiovascular risk in psoriatic patients detected by heart rate variability
      (HRV) analysis.
AB  - Patients affected by severe psoriasis have an increased prevalence of
      cardiovascular () diseases as documented by several studies. Heart rate
      variability (HRV) is a noninvasive method to evaluate the autonomic control of
      the sinus node. In this study, HRV analysis has been used to evaluate whether
      young patients with moderate cutaneous psoriasis have increased cardiovascular
      (CV) risk, in absence of CV comorbidities. Our data indicate an imbalance toward
      the sympathetic arm of the autonomic cardiac modulation. As the increase in
      sympathetic activity may be associated with a higher CV risk, moderate psoriasis
      could be considered to be an independent CV risk factor.

PMID- 25381986
TI  - Lipid profile of rheumatoid arthritis patients treated with anti-tumor necrosis
      factor-alpha drugs changes according to disease activity and predicts clinical
      response.
AB  - Patients with active rheumatoid arthritis (RA) frequently show an atherogenic
      lipid profile, which has been linked with the inflammatory reaction. Inflammatory
      cytokines, and particularly tumor necrosis factor-alpha (TNF-alpha), are
      implicated in the pathogenesis of both atherosclerosis and RA, and also involved
      in the development of the impaired lipid profile detected in active RA. Although
      anti-TNF-alpha agents have been proven effective in controlling joint damage and
      systemic inflammation, controversy remains about the effect of these drugs on the
      lipid profile; therefore, the aim of our study was to investigate the effect of
      anti-TNF-alpha treatment, in combination with disease-modifying anti-rheumatic
      drugs (DMARDs) and corticosteroid therapy, on the lipid profile of patients with
      active RA. Our data suggest that the combination anti-TNF-alpha/DMARDs/steroids
      do not significantly interfere with the lipid profile of RA patients. However,
      analysis of clinical response data showed that patients achieving low disease
      activity or remission seem to have a protective lipid profile, suggesting that
      better control of inflammation and disease activity can affect lipid metabolism.
      The available evidence indicates that high inflammation interferes with lipid
      metabolism, whereas good control of the chronic inflammatory state may positively
      influence the lipid profile and cardiovascular risk. Low cholesterol levels at
      baseline could predict a favorable outcome with anti-TNF-alpha treatment, but
      these data need to be confirmed by large prospective studies with long-term
      follow-up.

PMID- 25381988
TI  - The EPIPSOFIRE project: a preliminary report.
AB  - Psoriatic arthritis (PsA) is a musculoskeletal condition complicating psoriasis
      that can lead to joint deformity and disability; however, psoriatic patients may
      suffer from other kind of arthropathies that could be confused with PsA by
      nonrheumatologists. Our aim was to determine the prevalence of PsA and to
      determine the prevalence of other musculoskeletal conditions in a cohort of
      psoriatic patients. In this cohort, musculoskeletal discomfort was frequently
      reported, while inflammatory disorders were detected in <4% of subjects. The
      cohort lacked subjects with very long-standing psoriasis duration (>20 years) or
      severe cutaneous disease. Because musculoskeletal discomfort symptoms affected
      about 62% of patients, other disorders, particularly morphologic conditions, need
      careful evaluation in psoriasis subjects.

PMID- 25381989
TI  - Synthesis and antiaromatic properties of highly planar dithiaamethyrin.
AB  - 2,5-Bis(4-propyl-2-pyrrolyl)thiophene was reacted with aryl aldehydes to afford
      large porphyrinoids; [24]dithiaamethyrin(1.0.0.1.0.0) and
      [36]trithianonaphyrin(1.0.0.1.0.0.1.0.0). X-ray crystallography of the
      dithiaamethyrin revealed a highly planar ring structure with mean plane deviation
      (MPD) value of 0.053 A. A large positive NICS(0) value (+13.9 ppm) calculated for
      this planar 24pi system unambiguously indicates an antiaromatic character that is
      consistent with a remarkably low field (1) H chemical shift of the inner NH
      proton at 24.0 ppm. The magnitude of the paratropic ring current effect in the
      24pi amethyrin framework in the free base form and the diprotonated form was
      discussed on the basis of the MPD value and the NICS value. The present
      dithiaamethyrin is much more strongly antiaromatic than the dodecaalkylamethyrin
      in their free base forms, but the order inversed in their diprotonated forms. 

PMID- 25381990
TI  - Reversible cognitive, motor, and driving impairments in severe hypothyroidism.
AB  - BACKGROUND: Hypothyroidism has been associated with cognitive and motor
      impairments that are likely to constitute hazards in the operation of motor
      vehicles and a public safety risk. However, there is a paucity of data that would
      provide an evidence basis for recommendations to hypothyroid patients. The
      purpose of this study was to determine the specific neurological and
      psychological deficits consequent to hypothyroidism and whether they are of
      sufficient magnitude to impede the safe operation of motor vehicles. METHODS:
      Repeated measurements were obtained in euthyroid, hypothyroid, and euthyroid
      hormone replaced states of thyroid cancer outpatients, at an academic medical
      center, who underwent thyroid hormone withdrawal preparation for radioiodine
      scanning. Study design used a within-subjects longitudinal "A-B-A" with each
      subject tested at three visits in the same sequence: euthyroid, hypothyroid, and
      euthyroid for a total of 32 subjects. Data on clinical status and cognitive
      performance were collected using standard instruments, including ThyDQoL and
      ThySRQ measures, National Adult Reading Test, Boston Naming Test, Mini-Mental
      State Exam, Wechsler Adult Intelligence Test-Revised, Letter Fluency FAS, and
      Beck Depression Inventory. Fine-motor function was measured with an automated
      assessment panel, and driving performance on a commercial driving simulator.
      RESULTS: In severe hypothyroidism (median thyrotropin 83.2 mIU/L), fine-motor
      performance of hands and reaction times in emergency braking tests were slowed,
      as well as subjective slowing reported on structured clinical scales. Depression
      was present, typified by vegetative and mood alterations, but lacking reported
      guilt and lowered self-esteem seen in other types of depression. Cognitive
      impairment was characterized by declines on speeded executive tests. In contrast,
      episodic memory performance improved over time regardless of thyroid hormone
      status. Braking times increased in hypothyroidism by 8.5%, equivalent to reports
      of effects from a blood alcohol level of 0.082 g/100 mL (above the U.S. legal
      driving limit). CONCLUSIONS: Transient profound hypothyroidism is characterized
      by reversible depression, decreased fine-motor performance, slowed reaction
      times, and decreased processing speed. These data represent new empirical
      evidence that support the recommendation that complex activities requiring rapid
      responses, such as operating motor vehicles, should be avoided during
      hypothyroidism. This has broader implications regarding functional impairments
      and risk to public health.

PMID- 25381991
TI  - Quantitative analysis of sitagliptin using the (19)F-NMR method: a universal
      technique for fluorinated compound detection.
AB  - To expand the application scope of nuclear magnetic resonance (NMR) technology in
      quantitative analysis of pharmaceutical ingredients, (19)F nuclear magnetic
      resonance ((19)F-NMR) spectroscopy has been employed as a simple, rapid, and
      reproducible approach for the detection of a fluorine-containing model drug,
      sitagliptin phosphate monohydrate (STG). ciprofloxacin (Cipro) has been used as
      the internal standard (IS). Influential factors, including the relaxation delay
      time (d1) and pulse angle, impacting the accuracy and precision of spectral data
      are systematically optimized. Method validation has been carried out in terms of
      precision and intermediate precision, linearity, limit of detection (LOD) and
      limit of quantification (LOQ), robustness, and stability. To validate the
      reliability and feasibility of the (19)F-NMR technology in quantitative analysis
      of pharmaceutical analytes, the assay result has been compared with that of (1)H
      NMR. The statistical F-test and student t-test at 95% confidence level indicate
      that there is no significant difference between these two methods. Due to the
      advantages of (19)F-NMR, such as higher resolution and suitability for biological
      samples, it can be used as a universal technology for the quantitative analysis
      of other fluorine-containing pharmaceuticals and analytes. 

PMID- 25381993
TI  - Understanding the experiences of Mandarin-speaking patients diagnosed with life
      threatening cancer in Australia.
AB  - OBJECTIVE: People from ethnic minority groups who receive cancer care outside
      their country of origin may experience poor survival and psychological outcomes
      relative to that nation's majority groups. This exploratory qualitative study
      aimed to understand the experience of a large minority group of Mandarin-speaking
      cancer patients (MSCPs) after diagnosis and treatment of their cancer in
      Australia, with a view to delineate if cultural or linguistic factors affected
      the quality of care provided. METHOD: We employed an exploratory qualitative
      design involving interviews with 22 MSCPs who were treated during 2009 at the
      Peter MacCallum Cancer Centre (PMCC) in Melbourne, Australia. Participants were
      interviewed by a bilingual psychiatrist, audiotaped, transcribed in Mandarin, and
      then translated into English before being subjected to thematic analysis by two
      independent researchers. RESULTS: MSCPs experienced notable challenges as a
      result of both language difficulties and differing cultural approaches, which
      often limited their understanding of their disease and impeded their ability to
      access quality care and adequate support. The results call for Australia and
      other Western nations with increasingly diverse populations to consider how
      cancer care can be modified to better support people from minority groups to
      effectively cope with their diagnosis and treatment. SIGNIFICANCE OF RESULTS:
      This study raises several suggestions for service improvement, including the
      development of bilingual communication aids, improved educational opportunities
      for clinical staff to aid their mastery of cultural issues and effective
      interpreter consultations, and improved access to supportive services offering
      culturally specific strategies.

PMID- 25381992
TI  - High-resolution structure and mechanism of an F/V-hybrid rotor ring in a Na+
      coupled ATP synthase.
AB  - All rotary ATPases catalyse the interconversion of ATP and ADP-Pi through a
      mechanism that is coupled to the transmembrane flow of H(+) or Na(+).
      Physiologically, however, F/A-type enzymes specialize in ATP synthesis driven by
      downhill ion diffusion, while eukaryotic V-type ATPases function as ion pumps. To
      begin to rationalize the molecular basis for this functional differentiation, we
      solved the crystal structure of the Na(+)-driven membrane rotor of the
      Acetobacterium woodii ATP synthase, at 2.1 A resolution. Unlike known structures,
      this rotor ring is a 9:1 heteromer of F- and V-type c-subunits and therefore
      features a hybrid configuration of ion-binding sites along its circumference.
      Molecular and kinetic simulations are used to dissect the mechanisms of Na(+)
      recognition and rotation of this c-ring, and to explain the functional
      implications of the V-type c-subunit. These structural and mechanistic insights
      indicate an evolutionary path between synthases and pumps involving adaptations
      in the rotor ring. 

PMID- 25381994
TI  - Long Term Stability Evaluation of Prostacyclin Released from Biomedical Device
      through Turbiscan Lab Expert.
AB  - Therapeutic guidelines indicate prostacyclin as the first line of treatment in
      inflammation and vascular diseases. Prostacyclins prevent formation of the
      platelet plug involved in primary hemostasis by inhibiting platelet activation
      and, combined with thromboxane, are effective vasodilators in vascular damage.
      Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral
      Arterial Disease II guidelines indicates prostacyclins; in particular, Iloprost,
      as the first therapeutic option for treating peripheral arterial disease.
      However, therapeutic efficacy of Iloprost has witnessed several drawbacks that
      have occurred in patients receiving repeated weekly administration of the drug by
      intravenous infusions. Adverse reactions arose under perfusion with Iloprost for
      6 h and patient compliance was drastically decreased. Biomedical devices could
      provide a suitable alternative to overcome these drawbacks. In particular,
      elastomeric pumps, filled with Iloprost isotonic solution, could slowly release
      the drug, thus decreasing its side effects, representing a valid alternative to
      hospitalization of patients affected by peripheral arterial disease. However, the
      home therapy treatment of patients requires long-term stability of Iloprost in
      solution-loaded elastomeric pumps. The aim of this work was to investigate the
      long-term stability of Iloprost isotonic solution in biomedical devices using
      Turbiscan technology. Turbiscan Lab Expert (L'Union, France) predicts the long
      term stability of suspensions, emulsions and colloidal formulations by measuring
      backscattering and transmission of particulates dispersed in solution. The
      formulations were evaluated by measuring the variation of physical-chemical
      properties of colloids and suspensions as a function of backscattering and
      transmission modifications. In addition, the release profile of Iloprost isotonic
      solution from the biomedical device was evaluated. 

PMID- 25381995
TI  - Practical Application of Antidiabetic Efficacy of Lycium barbarum Polysaccharide
      in Patients with Type 2 Diabetes.
AB  - Lycium barbarum polysaccharide (LBP) has traditionally been used in Chinese
      medicine as a chief ingredient of Lycium barbarum (wolf berry/goji berry) for the
      treatment of various diseases with the symptoms of frequent drinking and
      urination. This study was conducted as a randomized, controlled clinical trial. A
      total of 67 patients with type 2 diabetes (30 in control group and 37 in LBP
      group) were enrolled in this prospective, randomized, double-blind study
      (administration at 300 mg/day body weight). In order to observe the hypoglycemic
      and lipid-lowering activity of LBP in patients with type 2 diabetes after dinner,
      various tests were conducted between control and LBP intervention groups in 3
      months. Although, the study had small sample size and short follow-up,
      significant findings were observed. The results of our study indicated a
      remarkable protective effect of LBP in patients with type 2 diabetes. Serum
      glucose was found to be significantly decreased and insulinogenic index increased
      during OMTT after 3 months administration of LBP. LBP also increased HDL levels
      in patients with type 2 diabetes. It showed more obvious hypoglycemic efficacy
      for those people who did not take any hypoglycemic medicine compared to patients
      taking hypoglycemic medicines. This study showed LBP to be a good potential
      treatment aided-agent for type 2 diabetes.

PMID- 25381996
TI  - Distribution of dense breasts using screening mammography in Korean women: a
      retrospective observational study.
AB  - OBJECTIVES: This retrospective observational study evaluated the distribution of
      dense breasts by age group among healthy Korean women. METHODS: Participants were
      women aged 30 years and older who voluntarily underwent screening mammography
      between January 2007 and December 2011. Women who received the Breast Imaging
      Reporting and Data System for mammographic density of 3 or 4 were defined as
      having dense breasts. The proportion of women with dense breasts (PDB, %) was
      calculated by dividing the number of participants with dense breasts by the total
      number of participants. RESULTS: Among the 231,058 women who participated, 78.15%
      were classified as having dense breasts. PDB was highest in the youngest age
      group (PDB=94.87%) and lowest in the oldest age group. The greatest difference in
      PDB between adjacent age groups was observed in the group aged 60-64 years.
      CONCLUSIONS: The results show that the proportion of dense breasts by age group
      increased in all age groups, except in those aged 35-39 years. These findings
      suggest an association between the age distribution of dense breasts and trends
      in breast cancer incidence. Further studies are needed to estimate the change in
      breast cancer incidence rate by age and the accumulation of fatty breast tissue
      in Korean women.

PMID- 25381997
TI  - Risk factors for maternal mortality in the west of Iran: a nested case-control
      study.
AB  - OBJECTIVES: With a gradual decline in maternal mortality in recent years in Iran,
      this study was conducted to identify the remaining risk factors for maternal
      death. METHODS: This 8-year nested case-control study was conducted in Hamadan
      Province, in the west of Iran, from April 2006 to March 2014. It included 185
      women (37 cases and 148 controls). All maternal deaths that occurred during the
      study period were considered cases. For every case, four women with a live birth
      were selected as controls from the same area and date. Conditional logistic
      regression analysis was performed and the odds ratio (OR) and its 95% confidence
      interval (CI) were obtained for each risk factor. RESULTS: The majority of cases
      were aged 20-34 years, died in hospital, and lived in urban areas. The most
      common causes of death were bleeding, systemic disease, infection, and pre
      eclampsia. The OR estimate of maternal death was 8.48 (95% CI=1.26-56.99) for
      advanced maternal age (>=35 years); 2.10 (95% CI=0.07-65.43) for underweight and
      10.99 (95% CI=1.65-73.22) for overweight or obese women compared to those with
      normal weight; 1.56 (95% CI=1.08-2.25) for every unit increase in gravidity
      compared to those with one gravidity; 1.73 (95% CI=0.34-8.88) for preterm labors
      compared to term labors; and 17.54 (95% CI= 2.71-113.42) for women with systemic
      diseases. CONCLUSIONS: According to our results, advanced maternal age, abnormal
      body mass index, multiple gravidity, preterm labor, and systemic disease were the
      main risk factors for maternal death. However, more evidence based on large
      cohort studies in different settings is required to confirm our results.

PMID- 25381998
TI  - Korean translation of the CONSORT 2010 Statement: updated guidelines for
      reporting parallel group randomized trials.
AB  - The Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement, updated
      in March 2010, includes a 25-item checklist and flow diagram. Adherence to this
      statement is a minimum requirement for the complete, clear, and transparent
      reporting of randomized trials. We translated the CONSORT 2010 Statement into
      Korean to promote the widespread adherence to CONSORT in South Korea and to
      facilitate the adoption of complete, clear, and transparent reporting. The Korean
      version of the CONSORT is available at http://www.e-epih.org/. 

PMID- 25382000
TI  - Simultaneous ionization and analysis of 84 anabolic androgenic steroids in human
      urine using liquid chromatography-silver ion coordination ionspray/triple
      quadrupole mass spectrometry.
AB  - Metal ion coordination ionspray (M(+) CIS) ionization is a powerful technique to
      enhance ionization efficiency and sensitivity. In this study, we developed and
      validated an analytical method for simultaneous ionization and analysis of 84
      anabolic androgenic steroids (65 exogenous and 19 endogenous) using liquid
      chromatography-silver ion coordination ionspray/triple-quadrupole mass
      spectrometry (LC-Ag(+) CIS/MS/MS). The concentrations of silver ions and organic
      solvents have been optimized to increase the amount of silver ion coordinated
      complexes. A combination of 25 MUM of silver ions and methanol showed the best
      sensitivity. The validation results showed the intra- (0.8-9.2%) and inter-day
      (2.5-14.9%) precisions, limits of detection (0.0005-5.0 ng/mL), and matrix effect
      (71.8-100.3%) for the screening analysis. No significant ion suppression was
      observed. In addition, this method was successfully applied to analysis of
      positive samples from suspected abusers and useful for the detection of the trace
      levels of anabolic steroids in human urine samples.

PMID- 25381999
TI  - Scaling of adult regional body mass and body composition as a whole to height:
      Relevance to body shape and body mass index.
AB  - OBJECTIVES: Adult body mass (MB) empirically scales as height (Ht) squared (MB ?
      Ht(2) ), but does regional body mass and body composition as a whole also scale
      as Ht(2) ? This question is relevant to a wide range of biological topics,
      including interpretation of body mass index (BMI). METHODS: Dual-energy X-ray
      absorptiometry (DXA) was used to quantify regional body mass [head (MH), trunk,
      arms, and legs] and whole-body composition [fat, lean soft tissue (LST), and bone
      mineral content (BMC)] in non-Hispanic (NH) white, NH black, Mexican American,
      and Korean adults participating in the National Health and Nutrition Examination
      Survey (NHANES; n = 17,126) and Korean NHANES (n = 8,942). Regression models were
      developed to establish Ht scaling powers for each measured component with
      adjustments for age and adiposity. RESULTS: Exploratory analyses revealed a
      consistent scaling pattern across men and women of the four population groups:
      regional mass powers, head (~0.8-1) < arms and trunk (~1.8-2.3) < legs (~2.3
      2.6); and body composition, LST (~2.0-2.3) < BMC (~2.1-2.4). Small sex and
      population differences in scaling powers were also observed. As body mass scaled
      uniformly across the eight sex and population groups as Ht(~2) , tall and short
      subjects differed in body shape (e.g., MH/MB ? Ht(-~1) ) and composition.
      CONCLUSIONS: Adult human body shape and relative composition are a function of
      body size as represented by stature, a finding that reveals a previously
      unrecognized phenotypic heterogeneity as defined by BMI. These observations
      provide new pathways for exploring mechanisms governing the interrelations
      between adult stature, body morphology, biomechanics, and metabolism.

PMID- 25382001
TI  - Baseline sensitivity of T cells to alpha-IFN correlates with sustained
      virological response to IFN-based triple therapy in HCV infection.
AB  - Chronic infection with HCV is a public health problem with approximately 170
      million people infected worldwide. Interferon alpha (IFNalpha) sensitivity in
      liver and IL28B genotype has been identified as important determinants of HCV
      clearance in the setting of pegylated interferon/ribavirin treatment. Herein, we
      explored IFNalpha sensitivity in PBMC from 21 healthy donors and 21 HCV-infected
      patients treated with pegylated interferon/ribavirin and HCV nonstructural
      protein-3 inhibitors (i.e. telaprevir/boceprevir). We explored phospho-STAT1
      level as read-out for IFN signalling pathway activation in PBMC, T cells and
      monocytes and correlated results with virological response. We found that PBMC
      from healthy donors are desensitized to IFNalpha after priming and challenged
      with IFNalpha, with a subsequent decrease of phospho-STAT1 and interferon
      stimulated genes. Furthermore, we show that CD3+ T cells, but not monocytes,
      become desensitized after 4 weeks of treatment, with a significant decrease of
      phospho-STAT1 after ex vivo IFNalpha stimulation. Finally, we identified baseline
      phospho-STAT1 level in CD3+ T cells as a potential biomarker of sustained
      virological response, regardless of the IL28B genotype. In the upcoming costly
      era of IFN-sparing regimen, baseline IFNalpha sensitivity could act as biomarker
      to define cost-effectiveness strategies of treatment by identifying patients who
      will or will not respond to IFN-based treatments.

PMID- 25382002
TI  - Metformin promotes irisin release from murine skeletal muscle independently of
      AMP-activated protein kinase activation.
AB  - AIM: Irisin, a novel myocyte-secreted hormone mediating beneficial effects of
      exercise on metabolism, is supposed to be an ideal therapeutic target for
      metabolic disorders such as obesity and diabetes. Here, we investigated the
      potential effects of metformin and glibenclamide, two antidiabetic medicines, on
      irisin release in mouse. METHODS: Wild-type and diabetic obese db/db mice were
      administrated with metformin and glibenclamide for 2 weeks, and cultured C2C12
      myotubes were treated by metformin. Expression of irisin precursor FNDC5 was
      measured and blood irisin concentration was detected. AMP-activated protein
      kinase (AMPK) was blocked by chemical inhibitor compound C or knocking down with
      specific siRNA. RESULTS: The mRNA and protein expression of FNDC5 in skeletal
      muscle and blood irisin concentrations were lower in diabetic db/db mice than
      those in wild-type mice. Metformin and glibenclamide decreased blood glucose in
      db/db mice. Metformin, but not glibenclamide, increased intramuscular FNDC5
      mRNA/protein expression and blood irisin levels. Additionally, the reductions of
      blood glucose and body weight in metformin-treated db/db mice were positively
      associated with blood irisin concentrations. In C2C12 myotubes, metformin
      upregulated intracellular FDNC5 mRNA/protein expression and promoted irisin
      release. Although metformin activated AMPK signalling in skeletal muscle cells,
      disrupting of AMPK signalling by chemical inhibitor or siRNA-mediated knockdown
      did not abolish the promoting effect of metformin on irisin release. CONCLUSION:
      Metformin promotes irisin release from murine skeletal muscle into blood,
      independently of AMPK pathway activation. Our results suggest that stimulation of
      irisin may be a novel molecular mechanism of metformin which is widely used for
      treatment of metabolic disorders.

PMID- 25382003
TI  - [Bortezomib-based therapy in patients with light chain deposition disease].
AB  - Light chain deposition disease (LCDD) is a rare systemic condition caused by
      monoclonal proliferation of terminally differentiated B-lymphocytes with
      production of free light chains and their deposition in kidneys or other organs.
      The aim of our study is to show the pitfalls of the diagnostics, and to
      demonstrate the effect of bortezomib-based therapy on a series of 4 patients with
      LCDD, from the point of hematological and organ therapeutic response. We include
      that bortezomib based treatment provides rapid and effective hematological
      response. It is, however, often accompanied by adverse events, especially within
      intensive treatment schedules. The most serious adverse effects includes
      peripheral neuropathy, which might be dose or treatment-limiting. Less intensive
      regimens ("bortezomib weekly") suggest an alternative with expectation of lower
      incidence of adverse effects. Autologous stem cell transplantation is a
      recommended and relatively safe approach in convenient candidates. Organ response
      is significantly delayed after hematological response, and organ damage by light
      chain deposits might not be fully reversible.

PMID- 25382004
TI  - [Infective endocarditis in Tabor district in years 2009-2013].
AB  - AIM: To find out an average incidence of infective endocarditis (IE) in Tabor
      district in a monitored period of time and compare the obtained data with
      previously published national study. METHODS: Retrospective monocentric
      observational study monitoring occurence and characteristics of infective
      endocarditis in a defined region in years 2009-2013. Only patients with proved
      and treated infective endocarditis and patients whose diagnosis was revealed by
      autopsy were involved. RESULTS: In the monitored time 39 cases of infective
      endocarditis occured, which means that the average incidence was 7.8 cases on 100
      000 people per year. Median age in the time of diagnosis was 67. The group of
      patients was strongly dominated by men, who were affected three times more often
      than women. Almost the same rates of infective endocarditis were localized on
      mitral (36 %) and aortic (33 %) valve and electrode of a pacemaker (31 %). In
      comparison with the reference study there were more pacemaker-related infections
      detected. Two thirds of infections were caused by staphylococci. That means a
      prominent growth when compared to the pilot study. On the contrary, there was no
      significant change in mortality. CONCLUSION: Characteristic features of infective
      endocarditis are evolving, patients in-hospital mortality rate is high, about 30
      %. The disease by itself is a poor prognostic factor in a one-year mortality
      rate.Key words: incidence infective - infective endocarditis.

PMID- 25382005
TI  - [The occurrence of agranulocytosis due to antithyroid drugs in a cohort of
      patients with Graves disease treated with radioactive iodine 131I during 14
      years].
AB  - INTRODUCTION: Agranulocytosis is a serious complication of antithyroid drugs
      (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the
      occurrence of agranulocytosis in Graves disease (GD) patients admitted for
      radioactive iodine 131I (RAI) treatment to our thyroid unit. PATIENTS AND
      METHODS: We analyzed retrospectively a cohort of 603 GD patients (500 women and
      103 men; mean age 51.5 +/- 12.7 years) who received RAI between 1999 and 2012. Of
      them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36
      %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU). RESULTS:
      Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603.
      All of them were women (mean age 48.7 years; range 23-78). In 4 patients,
      agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After
      recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg
      MMI/day (range 9-40). No agranulocytosis due to PTU was found in our cohort. The
      time from beginning ATD treatment to agranulocytosis was 20-41 days. In 5
      patients there was a development of fever, while in 2 patients the complication
      was diagnosed from routine blood count. The mean duration of agranulocytosis was
      5.9 days (range 4-8). CONCLUSION: Agranulocytosis incidence in our cohort of
      patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5
      %. In all patients, agranulocytosis occurred early, and in one third it was
      asymptomatic when found. The aim of our report is to bring attention to a
      relatively rare, but potentially serious, complication of ATD treatment.

PMID- 25382006
TI  - [The user's reporting from the national registry of catheter aortic valve
      implantations (Czech TAVI Registry): the possibilities of the analytical reports
      based on the database system TrialDB2].
AB  - Assessment of the treatment procedures and their results is increasingly
      important in current medicine. The emphasis is put on an effective use of the
      health technologies (HTA). Unlike randomised studies, which involve strictly
      selected groups of patients who meet inclusion and exclusion criterias, the
      multicentre clinical registries provide a real-life picture of the treatment
      safety and effectiveness. Well prepared registries involve both research database
      and a friendly user interface enabling collection of parametric and easily
      analyzable data. Although there are some technological aspects aiming to ensure a
      maximum quality of entered data, cooperation with the users and data managers is
      essential. Such a registry, otherwise meaningful, must provide answers to
      previously defined medical hypotheses. Regular feedback to users (so called
      benchmarking or reporting) is considered to be of key importance. The Czech TAVI
      Registry (CTR) is a good example of reaching all of the above defined criterias.
      This registry contains data of approximately 95 % of all transcatheter aortic
      valve implantations (TAVI) performed in the Czech Republic. It is based on a
      general system aimed at the design of clinical trials, namely the TrialDB2 (a
      database system for clinical registries developed by the Institute of
      Biostatistics and Analyses at the Masaryk University (IBA MU). CTR has been run
      as an English-language version under the auspices of the Czech Society of
      Cardiology and represents one of the top-quality registries maintained by IBA MU.
      This paper presents the currently available database systems and some reports
      from this particular registry.

PMID- 25382007
TI  - [Therapeutic monitoring of vancomycin in routine clinical practice].
AB  - Therapeutic drug monitoring (TDM) is specific method of clinical pharmacology for
      monitoring of the therapy using measurement of drug serum concentrations followed
      interpretation and good cooperation with clinician. TDM help clinicians to
      quickly optimize vancomycin dosing regimens to maximize the clinical effect and
      minimize the toxicity of the drugs. Minimum serum vancomycin trough
      concentrations should always be maintained above 10 mg/L to avoid development of
      resistance, neverthelles trough concentrations > 20 mg/L are not recommended
      because of the risk of nephrotoxicity. For serious infections vancomycin trough
      concentrations of 15-20 mg/L are recommended and for a pathogen with an MIC of 1
      mg/L, the minimum trough concentration would have to be at least 15 mg/L to
      generate the target AUC24/MIC 400 (area under the curve/minimal inhibitory
      concentration). In non-complicated infections trough concentrations of 10-15 mg/L
      should be sufficient. For continuous infusions of vancomycin target steady-state
      concentration values of 15-25 mg/L have been advocated for critically ill
      patients.Key words: therapeutic monitoring - trough concentration - vancomycin. 

PMID- 25382008
TI  - [Pulmonary hypertension - disease mechanisms].
AB  - Pulmonary hypertension (PH) is known for its variable etiology. PH
      pathophysiology is very complex and our therapeutic options are limited. Most of
      known underlying disease mechanisms play a role across all etiological groups of
      PH, and they are followed by the same morphological and functional changes of
      pulmonary vasculature. Mostly, we are not able to determine whether one
      particular mechanism works as a cause or consequence in the chain of events. An
      imbalance between vasoconstriction and vasodilation becomes the major functional
      change of pulmonary vasculature in PH. The main morphological changes (termed
      together as "remodeling") include cell hyperplasia of pulmonary artery leading to
      its thickening and narrowing, and impaired regulation of extracellular matrix
      production leading to reduction in its elasticity. As a result of all these
      changes, the peripheral vascular resistance in pulmonary vascular bed rises, thus
      increasing afterload of the right ventricle and finally progressing to its
      failure. This review aims to summarize and explain the nature of the functional
      and histological changes in pulmonary arteries which occur in pulmonary
      hypertension, separately define the role of endothelium and pulmonary artery
      myocytes, and discuss the most important known pathophysiological mechanisms that
      lead to these changes.

PMID- 25382009
TI  - [Monoclonal gammopathy of undetermined significance and asymptomatic multiple
      myelom in the year 2014 ].
AB  - Presence of monoclonal immunoglobulin in serum or urine is a relatively common
      event affecting about 3.2 % of people over 50. Isolated increase of only one type
      of free light chain, either kappa or lambda, is detected in 0.7-0.8 % of people
      over 50. Most people with monoclonal immunoglobulin meet the criteria of the so
      called "mono-clonal gammopathy of undetermined significance (MGUS)". MGUS is
      defined by concentration of monoclonal immunoglobulin in serum < 30 g/l, number
      of plasma cells in the bone marrow < 10 % and the absence of symptoms of multiple
      myeloma and other lymphoproliferative diseases. A proportion of people with MGUS
      gradually progresses from asymptomatic into symptomatic myeloma or other
      malignant lymphoproliferative disease requiring treatment. Therefore, MGUS is
      considered to be one of the most common premalignant conditions with an average
      risk of transformation into malignant disease of 1 % per year. Monoclonal
      gammopathy of IgG and IgA subtype can develop into multiple myeloma. Light chain
      monoclonal gammopathy can develop not only into light chain multiple myeloma but
      also into AL-amyloidosis and light chain deposition disease (amorphous deposits
      of light chains damaging organs). IgM monoclonal gammopathy may develop into
      Waldenstrom macroglobulinemia or other lymphoproliferative disorder, or into rare
      IgM subtype of multiple myeloma. Unfortunately, people with MGUS are threatened
      by more than an increased risk of transformation into multiple myeloma or other
      severe hematologic disease. Pre-malignant clone of plasma cells in the bone
      marrow causes changes in the bone marrow that directly affect the person. For
      people with MGUS, there is an increased incidence of osteoporosis and increased
      fracture risk when compared to the general population. People with MGUS also have
      an increased risk of bacterial infections and thromboembolic complications
      compared with the same age population without MGUS. Clonal plasma cells, which
      are the basis of MGUS, may in some cases produce toxic monoclonal immunoglobulin
      which can damage the body's own antibody activity by binding to specific antigens
      (such as cold agglutinin disease), or their deposits in organs (e.g. kidney
      damage) or physical properties (e.g. cryoglobulinemia). Therefore, it is
      recommended that this group of people is regularly checked with the aim to
      capture not only transformation into symptomatic multiple myeloma or another
      malignant disease, but also the formation of the above-mentioned complications.
      Moreover, it is recommended to monitor patients with asymptomatic myeloma and to
      initiate treatment only after symptoms of multiple myeloma are observed. In 2014,
      discussion of subdivision of subgroups of patients with asymptomatic myeloma with
      high ( 80 %) probability of early (within 2 years) transformation in multiple
      myeloma which would be beneficial for early initiation of treatment is ongoing.
      According to first proposals, patients with asymptomatic myeloma that meet at
      least one of the three conditions: more than 60 % of plasma cells in the bone
      marrow, ratio of free light kappa and lambda chains is greater than 100 or less
      than 0.01, or multiple focal lesions on whole-body MRI of the skelet. The review
      contains current opinions on prognostic classification and appropriate intervals
      and extent of control examinations.

PMID- 25382010
TI  - [The Association of atherothrombosis and thrombophilias - genetic aspects].
AB  - Thrombosis in the arterial or venous vascular systems is preceded by a complex
      interplay between environmental and genetic factors, and it is the underlying
      cause of several common complex diseases. The genomewide association approach has
      proved successful in identifying loci associated with cardiovascular disease and
      related risk factors. However, much work remains to identifyning the culprit
      genes and causal variants as well as the mechanisms whereby they influence
      disease development and progression. In-depth studies of previously identified
      disease-associated loci are expected to improve our understanding of the
      pathophysiology of cardiovascular disease and identify novel targets for
      treatment. In the field of atherothrombosis and thrombophilia are significant
      results from association studies focused on the area of coronary artery disease,
      ischemic stroke, venous thromboembolism.Key words: atherosclerosis -
      atherothrombosis - coronary artery disease - genomewide association study (GWAS) 
      myocardial infarction - single nucleotide polymorphism (SNP) - thrombophilia -
      venous thromboembolism. 

PMID- 25382011
TI  - [Optimal way of administration of high dose intravenous furosemide - continuous
      infusion or bolus?].
AB  - INTRODUCTION: Furosemide is a loop diuretic used in states of volume overload.
      The need for high doses is due to its reduced efficacy caused by lower
      concentration of furosemide achieved at the site of action in the renal tubule
      lumen and adaptation mechanisms. High doses have been associated with the
      development of ionic dysbalance, direct toxicity and intravascular volume
      fluctuations. The way of furosemide administration (intermitent versus
      continuously) to influence efficacy and safety is contradictory evaluated in EBM.
      AIM: The aim of this study is to analyze the available data for evaluation of the
      efficacy and safety of intermittent versus continuous dose regimens. METHODS: A
      systematic search on PubMed from 1990 to 2013 using the keywords - furosemide,
      loop diuretic, bolus, continuous infusion, efficacy, safety, heart failure, ICU,
      critical care. CONCLUSION: The pharmacokinetic and pharmacodynamic knowledge of
      furosemide create a theoretical assumption for the preference of continuous
      infusions before intermittent boluses. Assessement of available studies, however,
      yet in clinical practice did not proof the advantage of one over the other route
      of administration.

PMID- 25382012
TI  - [Gout and cardiovascular risk].
AB  - Gout represents a heterogeneous group of metabolic disorders characterized by
      production and deposition of sodium urate crystals in various tissues. The
      consequence of this deposition in musculoskeletal system causes gouty arthritis
      often presented by acute recurrent attack and development of chronic tophi. The
      most important risk factor is hyperuricemia which means higher level of acid uric
      in blood. Gout or hyperuricemia alone represents significant independent risk
      factor of all-cause and cardiovascular morbidity and mortality. Many patients
      with hyperuricemia and gout have risk factors typical for metabolic syndrome or
      suffer from other diseases. Maintaining the acid uric serum levels below 360
      umol/l, dissolution of sodium urate deposits and prevention of their formation
      are crucial for successful treatment. In addition to the non-pharmacological
      approaches, medications as xanthine oxidase inhibitors or uricosuric agents are
      used for lowering serum uric acid levels in treatment of chronic hyperuricemia.
      The successful treatment may contribute to reduce cardiovascular risk in patients
      with hyperuricemia and gout.Key words: gout - hyperuricemia - cardiovascular risk
      - uric acid - metabolic syndrome - treatment. 

PMID- 25382013
TI  - [How are changing the therapy options in obese diabetic type 2 patients].
AB  - Classical consequence of treatment with anti-diabetic agents, including insulin,
      is weight gain which enhances insulin resistance and leads to a further increase
      in drug dose. This creates an unwanted cycle. Administration of weight neutral
      anti-diabetic drugs has broken this scenario. Another option is to use anti
      obesity agents, but actually many of them are not available. However, in the
      United States, two new drugs have been used in past two years. The most important
      change in the treatment of obese type 2 diabetes patients is administration of
      anti-diabetic agents that reduce weight. These agents are well-known incretin
      analogs characterized by their unpleasant injecting administration. However,
      application becomes easier and the drugs are administered for the866 longer time
      period. Even greater change in treatment is administration of gliflozins.
      Dapagliflozin and empagliflozin enter almost simultaneously to the Czech
      Republic. The new class of drugs has very complex metabolic effect and in
      particular significantly reduces the weight even in patients treated with
      insulin. The treatment options have significantly expanded for obese type 2
      diabetes patient in course of this year.

PMID- 25382014
TI  - Effect of pre- and post-combined multidoses of epigallocatechin gallate and
      coenzyme Q10 on cisplatin-induced oxidative stress in rat kidney.
AB  - The nephroprotective effect of coenzyme Q10 and epigallocatechin gallate was
      investigated in rats with acute renal injury induced by a single nephrotoxic dose
      of cisplatin. Two days prior to cisplatin administration, epigallocatechin
      gallate and coenzyme Q10 alone and in four different combinations were given for
      6 days. The treatment with antioxidants significantly protected the cisplatin
      induced increase in the levels of blood urea nitrogen and serum creatinine. Both
      the antioxidants alone or in different combinations significantly compensated the
      increased malondialdehyde and reduced glutathione levels. Moreover, the decrease
      in the activities of superoxide dismutase, catalase, and glutathione peroxidase
      and the concentration of selenium, zinc, and copper ions were significantly
      attenuated in renal tissue. In conclusion, epigallocatechin gallate and coenzyme
      Q10 are equally effective against cisplatin-induced nephrotoxicity, whereas the
      intervention by combining these two antioxidants was found to be highly effective
      at low doses in attenuating oxidative stress in rat kidney. 

PMID- 25382015
TI  - Univalent gallium complexes of simple and ansa-arene ligands: effects on the
      polymerization of isobutylene.
AB  - Using [Ga(C6 H5 F)2 ](+) [Al(OR(F))4 ](-) (1) (R(F) =C(CF3)3) as starting
      material, we isolated bis- and tris-eta(6) -coordinated gallium(I) arene complex
      salts of p-xylene (1,4-Me2 C6 H4), hexamethylbenzene (C6 Me6 ), diphenylethane
      (PhC2 H4 Ph), and m-terphenyl (1,3-Ph2 C6 H4): [Ga(1,4-Me2 C6 H4 )2.5 ](+)
      (2(+)), [Ga(C6 Me6 )2 ](+) (3(+)), [Ga(PhC2 H4 Ph)](+) (4(+)) and [(C6 H5 F)Ga(MU
      1,3-Ph2 C6 H4)2 Ga(C6 H5 F)](2+) (5(2+)). 4(+) is the first structurally
      characterized ansa-like bent sandwich chelate of univalent gallium and 5(2+) the
      first binuclear gallium(I) complex without a Ga-Ga bond. Beyond confirming the
      structural findings by multinuclear NMR spectroscopic investigations and density
      functional calculations (RI-BP86/SV(P) level), [Ga(PhC2 H4 Ph)](+) [Al(OR(F))4](
      ) (4) and [(C6 H5 F)Ga(MU-1,3-Ph2 C6 H4)2 Ga(C6 H5 F)](2+) {[Al(OR(F) )4] (-)}2
      (5), featuring ansa-arene ligands, were tested as catalysts for the synthesis of
      highly reactive polyisobutylene (HR-PIB). In comparison to the recently published
      1 and the [Ga(1,3,5-Me3 C6 H3)2](+) [Al(OR(F))4](-) salt (6) (1,3,5-Me3 C6 H3
      =mesitylene), 4 and 5 gave slightly reduced reactivities. This allowed for
      favorably increased polymerization temperatures of up to +15  degrees C, while
      yielding HR-PIB with high contents of terminal olefinic double bonds (alpha
      contents=84-93 %), low molecular weights (Mn =1000-3000 g mol(-1)) and good
      monomer conversions (up to 83 % in two hours). While the chelate complexes
      delivered more favorable results than 1 and 6, the reaction kinetics resembled
      and thus concurred with the recently proposed coordinative polymerization
      mechanism.

PMID- 25382016
TI  - Alpha-helical cationic anticancer peptides: a promising candidate for novel
      anticancer drugs.
AB  - Cancer has become a serious concern in public health. Harmful side effects and
      multidrug resistance of traditional chemotherapy have prompted urgent needs for
      novel anticancer drugs or therapeutic approaches. Anticancer peptides (ACPs) have
      become promising molecules for novel anticancer agents because of their unique
      mechanism and several extraordinary properties. Most alpha-helical ACPs target
      the cell membrane, and interactions between ACPs and cell membrane components are
      believed to be the key factor in the selective killing of cancer cells. In this
      review, we focus on the exploitation of the structure and function of alpha
      helical ACPs, including the distinction between cancer and normal cells, the
      proposed anticancer mechanisms, and the influence of physicochemical parameters
      of alpha-helical ACPs on the biological activities and selectivity against cancer
      cells. In addition, the design and modification methods to optimize the cell
      selectivity of alpha-helical ACPs are considered. Furthermore, the suitability of
      ACPs as cancer therapeutics is discussed. 

PMID- 25382017
TI  - Non-adenosine nucleoside inosine, guanosine and uridine as promising
      antiepileptic drugs: a summary of current literature.
AB  - Adenosine (Ado) and some non-adenosine (non-Ado) nucleosides including inosine
      (Ino), guanosine (Guo) and uridine (Urd) are modulatory molecules in the central
      nervous system (CNS), regulating different physiological and pathophysiological
      processes in the brain such as sleep and epilepsy. Indeed, different drugs
      effective on adenosinergic system (e.g., Ado metabolism inhibitors, agonists and
      antagonists of Ado receptors) are being used in drug development for the
      treatment of epileptic disorders. Although (i) endogenous Ino, Guo and Urd showed
      anticonvulsant/antiepileptic effects (e.g., in quinolinic acid - induced seizures
      and in different epilepsy models such as hippocampal kindling models), and (ii)
      there is a need to generate new and more effective antiepileptic drugs for the
      treatment of drug-resistant epilepsies, our knowledge about antiepileptic
      influence of non-Ado nucleosides is far from complete. Thus, in this review
      article, we give a short summary of anticonvulsant/antiepileptic effects and
      mechanisms evoked by Ino, Guo, and Urd. Finally, we discuss some non-Ado
      nucleoside derivatives and their structures, which may be candidates as potential
      antiepileptic agents. 

PMID- 25382018
TI  - ATP synthase subunit alpha and LV mass in ischaemic human hearts.
AB  - Mitochondrial dysfunction plays a critical role in the development of ischaemic
      cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac
      tissue of ICM patients was analysed by quantitative differential electrophoresis
      (2D-DIGE) and mass spectrometry (MS) for the first time to provide new insights
      into cardiac dysfunction in this cardiomyopathy. We isolated mitochondria from LV
      samples of explanted hearts of ICM patients (n = 8) and control donors (n = 8)
      and used a proteomic approach to investigate the variations in mitochondrial
      protein expression. We found that most of the altered proteins were involved in
      cardiac energy metabolism (82%). We focused on ATPA, which is involved in energy
      production, and dihydrolipoyl dehydrogenase, implicated in substrate utilization,
      and observed that these molecules were overexpressed and that the changes
      detected in the processes mediated by these proteins were closely related.
      Notably, we found that ATPA overexpression was associated with reduction in LV
      mass (r = -0.74, P < 0.01). We also found a substantial increase in the
      expression of elongation factor Tu, a molecule implicated in protein synthesis,
      and PRDX3, involved in the stress response. All of these changes were validated
      using classical techniques and by using novel and precise selected reaction
      monitoring analysis and an RNA sequencing approach, with the total heart samples
      being increased to 24. This study provides key insights that enhance our
      understanding of the cellular mechanisms related to the pathophysiology of ICM
      and could lead to the development of aetiology-specific heart failure therapies.
      ATPA could serve as a molecular target suitable for new therapeutic
      interventions. 

PMID- 25382019
TI  - Robotic versus non-robotic instruments in spatially constrained operating
      workspaces: a pre-clinical randomized crossover study.
AB  - OBJECTIVE: To compare the effectiveness of robotic and non-robotic laparoscopic
      instruments in spatially constrained workspaces. MATERIALS AND METHODS: Surgeons
      performed intracorporeal sutures with various instruments within three different
      cylindrical workspace sizes. Three pairs of instruments were compared: 3-mm non
      robotic mini-laparoscopy instruments; 5-mm robotic instruments; and 8-mm robotic
      instruments. Workspace diameters were 4, 6 and 8 cm, with volumes of 50, 113 and
      201 cm(3) respectively. Primary outcomes were validated objective task
      performance scores and instrument workspace breach counts. RESULTS: A total of 23
      participants performed 276 suture task repetitions. The overall median task
      performance scores for the 3-, 5- and 8-mm instruments were 421, 398 and 402,
      respectively (P = 0.12). Task scores were highest (best) for the 3-mm non-robotic
      instruments in all workspace sizes. Scores were significantly lower when spatial
      constraints were imposed, with median task scores for the 4-, 6- and 8-cm
      diameter workspaces being 388, 415 and 420, respectively (P = 0.026). Significant
      indirect relationships were seen between boundary breaches and workspace size (P
      < 0.001). Higher breach counts occurred with the robotic instruments.
      CONCLUSIONS: Smaller workspaces limit the performance of both robotic and non
      robotic instruments. In operating workspaces <200 cm(3) , 3-mm non-robotic
      instruments are better suited for advanced bimanual operative tasks such as
      suturing. Future robotic instruments need further optimization if this technology
      is to be uniquely advantageous for clinical roles that involve endoscopic access
      to workspace-restricted anatomical areas.

PMID- 25382020
TI  - Picolinic and isonicotinic acids: a Fourier transform microwave spectroscopy
      study.
AB  - The rotational spectra of laser ablated picolinic and isonicotinic acids have
      been studied using broadband chirped pulse (CP-FTMW) and narrowband molecular
      beam (MB-FTMW) Fourier transform microwave spectroscopies. Two conformers of
      picolinic acid, s-cis-I and s-cis-II, and one conformer of isonicotinic acid have
      been identified through the analysis of their rotational spectra. The values of
      the inertial defect and the quadrupole coupling constants obtained for the most
      stable s-cis-I conformer of picolinic acid, evidence the formation of an O-H...N
      hydrogen bond between the acid group and the endocyclic N atom. The stabilization
      provided by this hydrogen bond compensates the destabilization energy due to the
      adoption of a -COOH trans configuration in this conformer. Its rs structure has
      been derived from the rotational spectra of several (13)C, (15)N, and (18)O
      species observed in their natural abundances. Mesomeric effects have been
      revealed by comparing the experimental values of the (14)N nuclear quadrupole
      coupling constants in the isomeric series of picolinic, isonicotinic, and
      nicotinic acids. 

PMID- 25382021
TI  - Umeclidinium bromide + vilanterol for the treatment of chronic obstructive
      pulmonary disease.
AB  - A solid scientific rationale and an increasing body of clinical evidence fully
      support the use of an antimuscarinic agent combined with a beta-agonist in
      chronic obstructive pulmonary disease. In this article, we focus on the
      development of an inhaled fixed dose combination (FDC) of two 24-h
      bronchodilators, umeclidinium bromide and vilanterol (UMEC/VI) (ANORO). Several
      pivotal clinical trials have documented the impact of this combination on lung
      function and other outcome measures such as quality of life, dyspnea, rescue
      medication use and exercise capacity, with no clinically meaningful treatment
      related changes in vital signs or clinical laboratory parameters. These results
      allow us to predict that UMEC/VI will have a role in the maintenance treatment of
      chronic obstructive pulmonary disease. It remains to determine its impact on
      exacerbations. In any case, trials comparing UMEC/VI with other dual
      bronchodilator FDCs, and also with inhaled corticosteroid/long-acting beta
      agonist FDCs, are needed to assess the advantages, if any, of UMEC/VI FDC over
      other therapies. 

PMID- 25382022
TI  - Diagnostic performances of FDG-PET/CT and diffusion-weighted imaging indices for
      differentiating benign pheochromocytoma from other benign adrenal tumors.
AB  - PURPOSE: The purpose of this study is to compare diagnostic performances of (18)F
      fluorodeoxyglucose (FDG) visual score, maximum standardized uptake value
      (SUVmax), ratio of adrenal SUVmax to liver SUVmax (A/L SUVmax), apparent
      diffusion coefficient (ADC) from diffusion-weighted imaging, and SUVmax/ADC ratio
      to differentiate adrenal pheochromocytoma from other benign tumors. METHODS:
      Eleven pheochromocytomas and 22 other benign tumors in 30 patients were included.
      FDG-based indices, ADC, and SUVmax/ADC ratio were compared between groups using
      the Mann-Whitney U test, and sensitivity, specificity, accuracy, and area under
      the curve (AUC) for diagnosing pheochromocytoma by receiver operating
      characteristic analyses. The correlation between SUVmax and ADC was analyzed
      using the Spearman's rank test. RESULTS: Pheochromocytoma showed significantly
      higher visual score (2.8 +/- 0.4 vs. 1.3 +/- 0.9), SUVmax (11.0 +/- 8.9 vs. 3.2
      +/- 1.4), A/L SUVmax ratio (3.96 +/- 3.48 vs. 0.96 +/- 0.51), and SUVmax/ADC
      ratio (10.6 +/- 8.09 vs. 2.28 +/- 0.98) (each P < 0.001) and significantly lower
      ADC (1.08 +/- 0.23 * 10(-3) mm(2)/s vs. 1.43 +/- 0.29 * 10(-3) mm(2)/s, P =
      0.003) than other benign tumors. Sensitivity, specificity, and accuracy for
      diagnosing pheochromocytoma were 100, 73, and 82% for visual score, 100, 86, and
      91% for both SUVmax and A/L SUVmax ratio, and 64, 100, and 88% for ADC and 82,
      95, and 91% for SUVmax/ADC ratio. No significant differences in AUC were found
      between FDG-based indices, ADC, and SUVmax/ADC ratio. A significant negative
      correlation was noted between SUVmax and ADC (rho = -0.36, P = 0.039).
      CONCLUSION: FDG-based indices and ADC appear comparably useful for
      differentiating pheochromocytoma from other benign adrenal tumors.

PMID- 25382024
TI  - A new copper species based on an azo-compound utilized as a homogeneous catalyst
      for water oxidation.
AB  - A new azo-complex [(L)Cu(II)(NO3)] [L = (E)-3-(pyridin-2-yldiazenyl)naphthalen-2
      ol (HL)], was prepared via a one-pot synthetic method at 60  degrees C and was
      structurally characterized by IR, EA, PXRD and single crystal X-ray diffraction.
      In addition, TGA studies indicated that the complex was stable in air. The redox
      properties were determined by cyclic voltammetry, which revealed that the complex
      could be utilized as a catalyst for water oxidation under mild conditions.
      Subsequently, the complex was employed as a catalyst to take part in water
      oxidation reaction in the presence of a Ce(IV) salt utilized as an oxidant at pH
      11 in PBS (Phosphate Buffered Saline) solution. The results suggested that the
      catalyst exhibited a high stability and activity toward water oxidation reaction
      under these conditions with an initial TOF of 4.0 kPa h(-1). Calculation
      methodology was performed to study the mechanism of the reaction, which revealed
      that in this catalytic process, the initial oxidation of Cu(II) to Cu(III)
      occurred by the formation of an intermediate "Cu(III)-O-O-Cu(III)". The formation
      of this intermediate, resulted in a release of oxygen and closing of the
      catalytic cycle.

PMID- 25382023
TI  - Coding mutations in SORL1 and Alzheimer disease.
AB  - OBJECTIVE: Common single nucleotide polymorphisms in the SORL1 gene have been
      associated with late onset Alzheimer disease (LOAD), but causal variants have not
      been fully characterized nor has the mechanism been established. The study was
      undertaken to identify functional SORL1 mutations in patients with LOAD. METHODS:
      This was a family- and cohort-based genetic association study. Caribbean
      Hispanics with familial and sporadic LOAD and similarly aged controls were
      recruited from the United States and the Dominican Republic, and patients with
      sporadic disease of Northern European origin were recruited from Canada.
      Prioritized coding variants in SORL1 were detected by targeted resequencing and
      validated by genotyping in additional family members and unrelated healthy
      controls. Variants transfected into human embryonic kidney 293 cell lines were
      tested for Abeta40 and Abeta42 secretion, and the amount of the amyloid precursor
      protein (APP) secreted at the cell surface was determined. RESULTS: Seventeen
      coding exonic variants were significantly associated with disease. Two rare
      variants (rs117260922-E270K and rs143571823-T947M) with minor allele frequency
      (MAF) < 1% and 1 common variant (rs2298813-A528T) with MAF = 14.9% segregated
      within families and were deemed deleterious to the coding protein. Transfected
      cell lines showed increased Abeta40 and Abeta42 secretion for the rare variants
      (E270K and T947M) and increased Abeta42 secretion for the common variant (A528T).
      All mutants increased the amount of APP at the cell surface, although in slightly
      different ways, thereby failing to direct full-length APP into the retromer
      recycling endosome pathway. INTERPRETATION: Common and rare variants in SORL1
      elevate the risk of LOAD by directly affecting APP processing, which in turn can
      result in increased Abeta40 and Abeta42 secretion.

PMID- 25382025
TI  - The "screwed aorta" after spinal deformity surgery.

PMID- 25382026
TI  - Aggregation and morphology control enables multiple cases of high-efficiency
      polymer solar cells.
AB  - Although the field of polymer solar cell has seen much progress in device
      performance in the past few years, several limitations are holding back its
      further development. For instance, current high-efficiency (>9.0%) cells are
      restricted to material combinations that are based on limited donor polymers and
      only one specific fullerene acceptor. Here we report the achievement of high
      performance (efficiencies up to 10.8%, fill factors up to 77%) thick-film polymer
      solar cells for multiple polymer:fullerene combinations via the formation of a
      near-ideal polymer:fullerene morphology that contains highly crystalline yet
      reasonably small polymer domains. This morphology is controlled by the
      temperature-dependent aggregation behaviour of the donor polymers and is
      insensitive to the choice of fullerenes. The uncovered aggregation and design
      rules yield three high-efficiency (>10%) donor polymers and will allow further
      synthetic advances and matching of both the polymer and fullerene materials,
      potentially leading to significantly improved performance and increased design
      flexibility. 

PMID- 25382028
TI  - Reproductive consequences of a matrilineal overthrow in rhesus monkeys.
AB  - Matrilineal overthrows in macaque societies are rare but devastating events,
      often resulting in severe morbidity, mortality, and loss of individual and group
      fitness. The handful of documented macaque overthrows provides scant evidence to
      reveal the severity or longevity of reproductive consequences resulting from such
      violent events. We analyzed archival records from semi-free ranging rhesus
      monkeys, Macaca mulatta, across 6 years (55 <= N <= 107, from 2007 to 2012)
      during which time a matrilineal overthrow occurred (in 2009) to test the
      hypothesis that extremely violent interactions such as a matrilineal overthrow
      would significantly reduce reproductive fitness for the involved matrilines and
      for the troop collectively. The matrilineal overthrow resulted in a significant
      increase in infant loss for the population from the previous year (chi(2)  =
      8.117, df = 1, P = 0.004), as evidenced by the fact that in 2009, but not in
      other years, the proportion of infants lost was greater than the proportion of
      viable infants (chi(2)  = 4.55, df = 1, P = 0.03). Moreover, the deposed
      matriline suffered 100% infant loss in 2009, a significant change from the
      previous year (chi(2)  = 7.87, df = 1, P = 0.005) while the attacking matriline
      suffered 50% infant loss (also a significant change from the previous year;
      chi(2)  = 4.44, df = 1, P = 0.035), with the uninvolved, lowest-ranking matriline
      showing no change in infant loss from the previous year (chi(2)  = 0.008, df = 1,
      P = 0.93). The deposed matriline did not produce viable offspring again until 3
      years later. We further found that rates of severe fighting (as indicated by the
      number of fight wounds requiring medical treatment) were positively correlated
      with infant loss across the 6 years of the study (r[s]  = 0.943, P = 0.005). Our
      data indicate that extreme periods of intra-group conflict, such as the
      matrilineal overthrow, have marked short-term consequences for individual
      fitness, and may be extreme examples of the long-term influences that group
      violence exerts on the mean fitness within a primate troop.

PMID- 25382027
TI  - Association of HLA-DR4/HLA-DRB1*04 with Vogt-Koyanagi-Harada disease: a
      systematic review and meta-analysis.
AB  - Human leukocyte antigen (HLA)-DR4/HLA-DRB1*04 has been reported to be a risk
      factor for Vogt-Koyanagi-Harada disease (VKH) with various strength of
      association. Its sub-alleles were also found to be associated with VKH. However
      the results were inconsistent. In this study, we systematically searched the
      related literature, pooled the odds ratios (ORs) and 95% confidence interval (CI)
      of association of HLA-DR4/HLA-DRB1*04 or its sub-alleles with VKH from individual
      studies, and explored the potential source of heterogeneity. A total of 1853 VKH
      patients and 4164 controls from 21 articles were included in this meta-analysis.
      The pooled OR of association of HLA-DR4/HLA-DRB1*04 and VKH was 8.42 (95% CI:
      5.69-12.45). There were significant heterogeneity (I(2) = 71%). Subgroup analysis
      indicated that ethnicity was the source of heterogeneity (all I(2) = 0, ORs
      ranged from 2.09-13.69 in subgroups). The sub-alleles, HLA-DRB1*0404 (OR = 2.57),
      0405 (OR = 10.31) and 0410 (OR = 6.52) increased the risk of VKH; 0401 (OR =
      0.21) protected VKH; while other sub-alleles were not associated with VKH. Our
      meta-analysis confirmed the association between VKH and HLA-DR4/DRB1*04, found
      the strength of association is different in different ethnic groups, and
      identified HLA-DRB1*0404, 0405 and 0410 as risk sub-alleles while 0401 as
      protective sub-allele. 

PMID- 25382029
TI  - Dislocation creation and void nucleation in FCC ductile metals under tensile
      loading: a general microscopic picture.
AB  - Numerous theoretical and experimental efforts have been paid to describe and
      understand the dislocation and void nucleation processes that are fundamental for
      dynamic fracture modeling of strained metals. To date an essential physical
      picture on the self-organized atomic collective motions during dislocation
      creation, as well as the essential mechanisms for the void nucleation obscured by
      the extreme diversity in structural configurations around the void nucleation
      core, is still severely lacking in literature. Here, we depict the origin of
      dislocation creation and void nucleation during uniaxial high strain rate tensile
      processes in face-centered-cubic (FCC) ductile metals. We find that the
      dislocations are created through three distinguished stages: (i) Flattened
      octahedral structures (FOSs) are randomly activated by thermal fluctuations; (ii)
      The double-layer defect clusters are formed by self-organized stacking of FOSs on
      the close-packed plane; (iii) The stacking faults are formed and the Shockley
      partial dislocations are created from the double-layer defect clusters. Whereas,
      the void nucleation is shown to follow a two-stage description. We demonstrate
      that our findings on the origin of dislocation creation and void nucleation are
      universal for a variety of FCC ductile metals with low stacking fault energies. 

PMID- 25382030
TI  - Complications related to early mobilization of mechanically ventilated patients
      on Intensive Care Units.
AB  - AIMS AND OBJECTIVES: To compare international literature on the detection of
      complications associated with early mobilization of mechanically ventilated
      patients in intensive care units (ICUs). BACKGROUND: Early mobilization of
      mechanically ventilated ICU patients is considered to be a more beneficial
      approach to treatment in intensive care; however, it remains unclear how safe
      this approach is and what complications to expect. SEARCH STRATEGIES: A
      systematic literature research in English and German was conducted in June 2013
      in the databases Pubmed, CINAHL, Cochrane library and MedPilot without limiting
      by year of publication. References of the included studies were screened and
      supplemented by manual search. INCLUSION AND EXCLUSION CRITERIA: Inclusion
      criteria were studies about mechanically ventilated adult patients on ICU, who
      were mobilized and reported complications. Excluded were studies that (a) did not
      differentiate between non-ventilated and ventilated patients, (b) did not report
      complications and (c) focused on in-bed mobilization. CONCLUSIONS: Of 952 titles,
      16 articles fit the criteria including 3 reviews and 13 clinical trials. The
      percentage of complications in clinical trials ranged between 0% and 16%. In
      total, 453 patients were mobilized 3613 times (up to walking with ventilation)
      with a complication mean rate of 3.9% (n = 144) using the inherent safety limits.
      No fall, cardiac arrest, or death was reported. Most complications were
      pulmonary, followed by haemodynamic ones. Serious complications that led to
      further consequences were observed in 0.3% (n = 10) of all mobilizations. The
      clinical studies have been carried out in trained, interdisciplinary teams with
      most of them using adapted algorithms for safety. RELEVANCE TO CLINICAL PRACTICE:
      Despite a low complication rate, a frame for safety during early mobilization
      including team training and adapted criteria is recommended.

PMID- 25382031
TI  - Delayed enhancement imaging in a contemporary patient cohort following correction
      of tetralogy of Fallot.
AB  - OBJECTIVE: To test the hypothesis that myocardial scars after repair of tetralogy
      of Fallot are related to impaired cardiac function and adverse clinical outcome.
      METHODS: A total of 53 patients were retrospectively analysed after repair of
      tetralogy of Fallot. The median patient age was 20 years (range 2-48). Cardiac
      MRI with a 1.5 T magnet included cine sequences to obtain volumes and function,
      phase-sensitive inversion recovery delayed enhancement imaging to detect
      myocardial scars, and flow measurements to determine pulmonary regurgitation
      fraction. In addition, clinical parameters were obtained. RESULTS: An overall 83%
      of patients were in NYHA class I. All patients with the exception of 2 (96%) had
      pulmonary insufficiency. Mean ejection fraction and end-diastolic volume index
      were 46% and 128 ml/m2 for the right ventricle and 54% and 82 ml/m2 for the left
      ventricle, respectively. Excluding enhancement of the septal insertion and
      prosthetic patches, delayed enhancement was seen in 11/53 cases (21%). Delayed
      enhancement of the right ventricle was detected in 6/53 patients (11%) and of the
      left ventricle in 5/53 patients (9%). The patient group with delayed enhancement
      was significantly older (p=0.003), had later repair (p=0.007), and higher left
      ventricular myocardial mass index (p=0.009) compared with the group without
      delayed enhancement. CONCLUSIONS: This study reveals that scarring is common in
      patients after surgical repair of tetralogy of Fallot and is associated with
      older age and late repair. However, there was no difference in right ventricular
      function, NYHA class, or occurrence of clinically relevant arrhythmias between
      patients with and those without myocardial scars.

PMID- 25382032
TI  - Synthesis of functionalized 2-salicyloylfurans, furo[3,2-b]chromen-9-ones and 2
      benzoyl-8H-thieno[2,3-b]indoles by one-pot cyclizations of 3-halochromones with
      beta-ketoamides and 1,3-dihydroindole-2-thiones.
AB  - Functionalized 2-salicyloylfurans and 2-benzoyl-8H-thieno[2,3-b]indoles were
      prepared under mild conditions by reaction of 3-halochromones with beta
      ketoamides and 1,3-dihydroindole-2-thiones, correspondently. The subsequent
      oxidative cyclization of the products resulted in formation of the corresponding
      furo[3,2-b]chromen-9-ones. These molecules could also be directly prepared from 3
      halochromones using a one-pot protocol. The cyclization reactions reported herein
      are mechanistically surprising as they proceed via the oxygen and not via the
      (more nucleophilic) nitrogen atom of the beta-ketoamide. 

PMID- 25382034
TI  - An aqueous rechargeable formate-based hydrogen battery driven by heterogeneous Pd
      catalysis.
AB  - The formate-based rechargeable hydrogen battery (RHB) promises high reversible
      capacity to meet the need for safe, reliable, and sustainable H2 storage used in
      fuel cell applications. Described herein is an additive-free RHB which is based
      on repetitive cycles operated between aqueous formate dehydrogenation
      (discharging) and bicarbonate hydrogenation (charging). Key to this truly
      efficient and durable H2 handling system is the use of highly strained Pd
      nanoparticles anchored on graphite oxide nanosheets as a robust and efficient
      solid catalyst, which can facilitate both the discharging and charging processes
      in a reversible and highly facile manner. Up to six repeated discharging/charging
      cycles can be performed without noticeable degradation in the storage capacity. 

PMID- 25382033
TI  - Effects of Helicobacter pylori infection and its eradication on lipid profiles
      and cardiovascular diseases.
AB  - BACKGROUND: We aimed to examine the relationship of current Helicobacter pylori
      infection with lipid profile and cardiovascular disease and its eradication
      effect. METHODS: Healthy subjects, who underwent routine checkup between October
      2003 and December 2007, were followed up until June 2009. Helicobacter pylori and
      lipid profiles were measured both baseline and follow-up. Multiple logistic
      regression models for odds ratios (ORs) and 95% confidence intervals (CIs) were
      used to estimate the effects of H. pylori infection and its eradication, on
      lipids and cardiovascular disease. RESULTS: Current infection with H. pylori with
      50.5% (6759/13383) at baseline increased low-density lipoprotein (LDL) and
      decreased high-density lipoprotein (HDL) than H. pylori-negative group.
      Successful eradication of H. pylori decreased the risk of high LDL compared with
      the persistent infection (OR 0.76, 95% CI 0.59-96), which was comparable to that
      of the persistent negative group (OR 0.82, 95% CI 0.70-0.97), and decreased the
      risk of low HDL (OR 0.68, 95% CI 0.49-0.96). Current infection of H. pylori
      increased the risk of cardiovascular disease (OR 3.27, 95% CI 1.31-8.14) at
      baseline, but its eradication failed to decrease the risk at a 2-year follow-up.
      However, persistent negative infection decreased the risk (OR 0.57, 95% CI 0.35
      0.94) comparing to persistent positive infection at follow-up. CONCLUSIONS:
      Current infection with H. pylori had a positive association with high LDL, low
      HDL, and cardiovascular disease. Successful H. pylori eradication decreased the
      risk of high LDL and low HDL, but did not reduce the risk of cardiovascular
      disease.

PMID- 25382037
TI  - Single micro-channel formation in a gap between probe electrodes by freezing an
      aqueous electrolyte.
AB  - A size-tunable micro-channel is fabricated in a gap between two probe electrodes
      by freezing aqueous KCl. The channel has been characterized by resistance
      measurements and channel blocking by resistive particles. The channel size can be
      varied by the temperature even after the preparation of the channel. The channel
      is potentially useful not only for size-selective particle counting but also for
      the size-selective separation or filtration of particles and macromolecules.

PMID- 25382038
TI  - Two-stage nicking enzyme signal amplification combined with DNAzyme amplification
      for the detection of bone morphogenetic protein 6 mRNA.
AB  - Highly sensitive detection of bone morphogenetic protein 6 (BMP6) mRNA is
      essential to monitor bone regeneration in the regenerating defects. In this work,
      we proposed a quantitative approach based on two-stage nicking enzyme signal
      amplification (NESA) and DNAzyme amplification for highly sensitive detection of
      BMP6 mRNA. The two-stage NESA involves two templates and two-stage amplification
      reactions under isothermal conditions. The first template contains two repeat
      sequences that could hybridize to the target RNA, triggering an exponential
      amplification. The amplified product was a short single-stranded DNA with the
      same sequence as the target RNA. The single-stranded DNA can trigger another
      linear NESA and produces a large amount of horseradish peroxidase (HRP)-mimicking
      G-quadruplex DNAzyme. This proposed assay showed a quantitative analysis of BMP6
      mRNA in a wide range from 1 fM to 100 nM with a detection limit of 0.01 fM.

PMID- 25382035
TI  - Enhancement of CD8(+) T-cell memory by removal of a vaccinia virus nuclear factor
      kappaB inhibitor.
AB  - Factors influencing T-cell responses are important for vaccine development but
      are incompletely understood. Here, vaccinia virus (VACV) protein N1 is shown to
      impair the development of both effector and memory CD8(+) T cells and this
      correlates with its inhibition of nuclear factor-kappaB (NF-kappaB) activation.
      Infection with VACVs that either have the N1L gene deleted (vDeltaN1) or contain
      a I6E mutation (vN1.I6E) that abrogates its inhibition of NF-kappaB resulted in
      increased central and memory CD8(+) T-cell populations, increased CD8(+) T-cell
      cytotoxicity and lower virus titres after challenge. Furthermore, CD8(+) memory T
      cell function was increased following infection with vN1.I6E, with more
      interferon-gamma production and greater protection against VACV infection
      following passive transfer to naive mice, compared with CD8(+) T cells from mice
      infected with wild-type virus (vN1.WT). This demonstrates the importance of NF
      kappaB activation within infected cells for long-term CD8(+) T-cell memory and
      vaccine efficacy. Further, it provides a rationale for deleting N1 from VACV
      vectors to enhance CD8(+) T-cell immunogenicity, while simultaneously reducing
      virulence to improve vaccine safety. 

PMID- 25382039
TI  - Solvent effect on the fluorescence response of hydroxycoumarin bearing a
      dipicolylamine binding site to metal ions.
AB  - The fluorescence behavior of a probe dpa-HC, which has a coumarin derivative that
      acts as a fluorophore and a dipicolylamine (DPA) unit that functions as a metal
      ion-recognition site, was investigated with various metal ions in aqueous and
      several non-aqueous solvents. In aqueous solution, the fluorescence of dpa-HC was
      enhanced by Zn(2+) and Cd(2+), but was quenched by other metal ions. On the other
      hand, in an acetonitrile solution, only Mg(2+) enhanced the fluorescence, and the
      addition of a small amount of water quenched this fluorescence. This dramatic
      selectivity change is explained by stabilization of a metal-dpa-HC complex due to
      acetonitrile coordination and ON-OFF switching of the intramolecular photoinduced
      electron transfer (PET) from the nitrogen lone pair of DPA to the coumarin
      derivative.

PMID- 25382040
TI  - Carbon nanofiber-based luminol-biotin probe for sensitive chemiluminescence
      detection of protein.
AB  - A carbon nanofiber-based luminol-biotin probe was synthesized for the sensitive
      chemiluminescence (CL) detection of a target protein by grafting luminol and
      biotin onto an oxidized carbon nanofiber. This carbon nanofiber was prepared by
      chemical vapor-deposition with methane in the presence of the Ni-Cu-MgO catalyst,
      which was followed by oxidization with HNO3-H2SO4 to produce a carboxyl group on
      the surface of the nanofiber. The material was grafted with luminol and biotin by
      means of a standard carbodiimide activation of COOH groups to produce
      corresponding amides. The substance was water-soluble and thus could be utilized
      as a sensitive CL probe for a protein assay. The probe showed highly specific
      affinity towards the biotin-labeled antibody via a streptavidin-biotin
      interaction. The detection limit for this model assay was approximately 0.2 pmol
      of the biotinized IgG spotted on a polyvinylidene fluoride (PVDF) membrane.
      Nonspecific binding to other proteins was not observed. Therefore, the
      synthesized carbon nanofiber-based CL probe may be useful for a sensitive and
      specific analysis of the target protein.

PMID- 25382041
TI  - A flow-injection system coupled to a micro-guard cartridge for monitoring a
      vinification process.
AB  - The present paper describes a flow-injection system coupled to a Micro-Guard
      cartridge and a miniaturized optical CCD detection system used to monitor the
      sugars (glucose/fructose) and ethanol content during alcoholic fermentation. The
      carrier stream (mobile phase) is composed of an aqueous sulfuric acid solution.
      The flow parameters were studied in order to obtain a good resolution and a wide
      dynamic concentration range, with a good repeatability. The relative standard
      deviation (RSD) obtained was inferior to 4%, for n = 3. It was possible to
      achieve a linear range of up to 12 g L(-1) of sugars and up to 2% (v/v) of
      ethanol with a detection limit of 2.3 g L(-1) and 0.4% (v/v), for sugars and
      ethanol concentrations, respectively. The proposed system was successfully
      applied to monitor a vinification process by the quantification of sugars and
      ethanol, and also in some finished port wines.

PMID- 25382042
TI  - Using second-derivative filters to assist in width estimations of size exclusion
      chromatography signal peaks with static light-scattering detections to obtain
      more accurate molecular weight.
AB  - Static light-scattering (LS) detection can determine the molecular weight (MW) of
      polymers eluted with size-exclusion chromatography (SEC) without using any
      standards when the differential refraction index (RI) of solutes are obtained. On
      the other hand, the noisy chromatographic signal peak acquired using a static LS
      detector often causes difficulty in peak-width recognition. This disadvantage
      limits the determination accuracy and precision of the MW values. This study
      developed one second-order derivative filtering procedure by convolving the
      original LS chromatogram against the second-derivative curve of one artificial
      Gaussian-shape chromatographic peak to suppress the noises and to correct the
      baseline of the chromatogram. More accurate estimations of the chromatographic
      peak widths of pullulan samples were achieved to improve the MW determination
      accuracy. For noisy original chromatography peaks of pullulan 5 k (SNR of
      approximately 10), the non-ideal determination accuracy of the MW values (9.3%)
      is improved to -1.3% with the assistance of the filtering procedures. 

PMID- 25382043
TI  - Adsorption behavior of beryllium(II) on copper-oxide nanoparticles dispersed in
      water: A model for (7)Be colloid formation in the cooling water for
      electromagnets at high-energy accelerator facilities.
AB  - The adsorption behavior of Be(II) on CuO nanoparticles dispersed in water was
      studied as a model for colloid formation of radioactive (7)Be nuclides in the
      cooling water used for electromagnets at high-energy proton accelerator
      facilities. An aqueous Be(II) solution and commercially available CuO
      nanoparticles were mixed, and the adsorption of Be(II) on CuO was quantitatively
      examined. From a detailed analysis of the adsorption data measured as a function
      of the pH, it was confirmed that Be(II) is adsorbed on the CuO nanoparticles by
      complex formation with the hydroxyl groups on the CuO surface (>S-OH) according
      to the following equation: n > S-OH + Be(2+) <=> (>S-O)n Be((2-n)+) + nH(+) (n =
      2, 3) S : solid surface. The surface-complexation constants corresponding to the
      above equilibrium, beta(s,2) and beta(s,3), were determined for four types of CuO
      nanoparticles. The beta(s,2) value was almost independent of the type of
      nanoparticle, whereas the beta(s,3) values varied with the particle size. These
      complexation constants successfully explain (7)Be colloid formation in the
      cooling water used for electromagnets at the 12-GeV proton accelerator facility.

PMID- 25382044
TI  - Reversible control of the equilibrium size of a single aerosol droplet by change
      in relative humidity.
AB  - Noncontact levitation of single micrometer-sized water droplets in air can be
      achieved by a laser trapping technique. The equilibrium size of a water droplet
      is quite sensitive to relative humidity in the surrounding gas phase. In order to
      investigate the physical and chemical properties of single water droplets in air
      as a function of the droplet size or solute concentration, laser trapping
      experiments were conducted under controlled humidity conditions. In this study,
      we developed a trapping chamber equipped with a relative humidity controller and
      demonstrated the reversible control of the equilibrium size of a single droplet
      levitated in air through a change in relative humidity. Furthermore, relative
      humidity was successfully evaluated by means of cavity enhanced Raman
      spectroscopy of a trapped water droplet. 

PMID- 25382045
TI  - Utilization of modified corn silk as a biosorbent for solid-phase extraction of
      Cr(III) and chromium speciation.
AB  - The ues of corn silk modified with diluted nitric acid (HNO3-MCS) as a novel
      biosorbent has been established for solid-phase extraction of Cr(III) and
      chromium speciation in water samples. The functional groups of the HNO3-MCS
      surface are favorable for the adsorption of Cr(III). Effective extraction
      conditions were optimized in both batch and column methods. At pH 3.0 - 6.0, a
      discrimination of Cr(III) and Cr(VI) is achieved on the HNO3-MCS surface. Cr(III)
      ions are retained onto the HNO3-MCS surface, however, the adsorption of Cr(VI) is
      negligible under the same conditions. The adsorption isotherm of HNO3-MCS for
      Cr(III) has been demonstrated in accordance with a linear form of the Langmuir
      equation, and the maximum adsorption capacity is 35.21 mg g(-1). The well fitted
      linear regression of the pseudo-second order model showed the indication of a
      chemisorption mechanism for the entire concentration range. Thermodynamic studies
      have shown that the adsorption process is spontaneous and endothermic. The
      adsorbed Cr(III) was quantitatively eluted by a nitric acid solution with
      detection by flame atomic absorption spectrometry (FAAS). With a sample volume of
      30 mL, a detection limit (3sigma) of 0.85 MUg L(-1) and a precision of 2.0% RSD
      at the 40 MUg L(-1) level were achieved. The concentration of Cr(III) could be
      accurately quantified within a linear range of 3 - 200 MUg L(-1). After Cr(VI)
      has been reduced to Cr(III) with hydroxylamine hydrochloride, the total amount of
      chromium was obtained, and the content of Cr(VI) was given by subtraction. The
      procedure was validated by analyzing chromium in a certified reference material
      (GBW (E) 080039). It was also successfully applied for the speciation of chromium
      in wastewater samples.

PMID- 25382046
TI  - Quantitative determination of bromine and iodine in food samples using ICP-MS.
AB  - Trace concentrations of bromine and iodine in food samples and certified
      reference materials (CRMs) were determined by an inductively coupled plasma-mass
      spectrometry (ICP-MS) technique after low-power microwave digestion and
      extraction into an aqueous quaternary ammonium hydroxide solution. The recovery
      after sample preparation was quantitative. The internal standard for the
      measurement of the analyte on ICP-MS was optimized in this study. The detection
      limits were 0.19 and 0.68 ng g(-1) for I and Br, respectively, when a 10 ng g(-1)
      Te solution as an internal standard was used, applying the signal of (125)Te. The
      high recovery and reproducibility are sufficient for the quantitative analysis of
      these elements, and the analytical procedure is recommended for the analysis of
      Br and I in various kinds of bio-samples.

PMID- 25382047
TI  - Simultaneous genotyping of single-nucleotide polymorphisms in alcoholism-related
      genes using duplex and triplex allele-specific PCR with two-step thermal cycles.
AB  - We developed a time- and cost-effective multiplex allele-specific polymerase
      chain reaction (AS-PCR) method based on the two-step PCR thermal cycles for
      genotyping single-nucleotide polymorphisms in three alcoholism-related genes:
      alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and MU-opioid receptor.
      Applying MightyAmp((r)) DNA polymerase with optimized AS-primers and PCR
      conditions enabled us to achieve effective and selective amplification of the
      target alleles from alkaline lysates of a human hair root, and simultaneously to
      determine the genotypes within less than 1.5 h using minimal lab equipment.

PMID- 25382049
TI  - Weight gain following subthalamic nucleus deep brain stimulation: a PET study.
AB  - Several hypotheses have been put forward to explain weight gain after deep brain
      stimulation (DBS), but none provides a fully satisfactory account of this adverse
      effect. We analyzed the correlation between changes in brain metabolism (using
      positron emission tomography [PET] imaging) and weight gain after bilateral
      subthalamic nucleus DBS in patients with Parkinson's disease. Body mass index was
      calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D
      glucose 3 months before and 4 months after the start of subthalamic nucleus deep
      brain stimulation in 23 patients with Parkinson's disease. Motor complications
      (United Parkinson's Disease Rating Scale [UPDRS]-IV scores) and dopaminergic
      medication were included in the analysis to control for their possible influence
      on brain metabolism. Mean +/- standard deviation (SD) body mass index increased
      significantly by 0.8 +/- 1.5 kg/m(2) (P = 0.03). Correlations were found between
      weight gain and changes in brain metabolism in limbic and associative areas,
      including the orbitofrontal cortex (Brodmann areas [BAs] 10 and 11), lateral and
      medial parts of the temporal lobe (BAs 20, 21, 22,39 and 42), anterior cingulate
      cortex (BA 32), and retrosplenial cortex (BA 30). However, we found no
      correlation between weight gain and metabolic changes in sensorimotor areas.
      These findings suggest that changes in associative and limbic processes
      contribute to weight gain after subthalamic nucleus DBS in Parkinson's disease.

PMID- 25382050
TI  - A systematic review of randomized controlled trials for management of persistent
      post-treatment fatigue in thyroid cancer survivors.
AB  - BACKGROUND: Fatigue that persists post-treatment is commonly reported by thyroid
      cancer (TC) survivors. METHODS: A systematic review of published English language
      randomized controlled trials (RCTs) on interventions for management of persistent
      post-treatment fatigue in TC was conducted. This review excluded studies on short
      term interventions used in preparation for radioactive iodine diagnostic scans or
      treatment. An electronic search was executed in six databases and supplemented by
      a hand search. Two reviewers independently reviewed all citations from the
      electronic search and relevant full-text studies. Two abstractors independently
      critically appraised included studies and abstracted the data. The data were
      qualitatively summarized. RESULTS: A total of 1086 unique citations and 25 full
      text studies were reviewed. Four studies summarizing the results of three RCTs
      were included. The interventions included: combination triiodothyronine with
      levothyroxine (L-T4) therapy compared to L-T4 alone (one RCT), reduction in
      degree of thyrotropin (TSH) suppression using L-T4 compared to maintenance of TSH
      suppression (one RCT), and supervised exercise compared to inactivity (two RCTs
      examining different fatigue outcomes in same population). Trial duration ranged
      from 10 weeks to six months. All trials had limitations, and the number of TC
      survivors included in respective RCTs ranged from 15 to 36. Hormonal treatment
      RCTs had mixed fatigue outcome results within respective trials. However,
      multiple measures suggesting improvement in fatigue were reported following the
      exercise intervention. CONCLUSIONS: There is paucity of RCTs to guide evidence
      based management of persistent post-treatment fatigue in TC survivors. RCTs of
      interventions for prevention or treatment of fatigue in TC survivors are needed.

PMID- 25382052
TI  - The response of DNA length and twist to changes in ionic strength.
AB  - We examine twist-stretch coupling of unconstrained DNA using polyelectrolyte
      theory as applied to a line-charge model along with published data on the ionic
      strength dependence of the twist angle. We conclude that twist-stretch coupling
      is negative: environmental changes that stretch free DNA, unconstrained by
      externally applied pulling or twisting forces, are accompanied by unwinding of
      the double helix. We also analyze a helical model and conclude that the observed
      unwinding of the DNA helix when ionic strength is decreased is driven by radial
      swelling of the helix.

PMID- 25382051
TI  - Hypoglycaemic effect of galactooligosaccharides in alloxan-induced diabetic rats.
AB  - This study was conducted to assess the effect of prebiotic
      galactooligosaccharides (GOS) on alloxan-induced diabetes in male Sprague-Dawley
      (SD) rats. Diabetes was induced by administration of alloxan (100 mg/kg) and rats
      were divided in 4 groups: normal control group (NCG), prebiotic control group
      (PCG), diabetic control group (DCG) and diabetic prebiotic group (DPG). While PCG
      and DPG were fed with GOS supplemented (10% w/w) diet, NCG and DCG were
      administered with basal diet. Rats were sacrificed after 42 d for collection of
      blood and liver. Faecal samples were collected at the interval of 7 d throughout
      the study for measurement of lactobacilli and coliform count. Feeding of GOS
      decreased or delayed the severity of diabetes by amelioration of diabetes
      associated markers including fasting blood glucose, haemoglobin, glycosylated
      haemoglobin triglycerides, total cholesterol, low density lipoproteins,
      creatinine and urea. GOS was also found to improve the levels of antioxidative
      enzymes (superoxide dismutase, catalase and glutathione peroxidase) in liver and
      blood. Improvement in lactobacilli count along with a concomitant decrease in
      coliform count was observed in GOS fed groups. 

PMID- 25382053
TI  - DNA movies and panspermia.
AB  - There are several ways that our species might try to send a message to another
      species separated from us by space and/or time. Synthetic biology might be used
      to write an epitaph to our species, or simply "Kilroy was here", in the genome of
      a bacterium via the patterns of either (1) the codons to exploit Life's non
      equilibrium character or (2) the bases themselves to exploit Life's quasi
      equilibrium character. We suggest here how DNA movies might be designed using
      such patterns. We also suggest that a search for mechanisms to create and
      preserve such patterns might lead to a better understanding of modern cells.
      Finally, we argue that the cutting-edge microbiology and synthetic biology needed
      for the Kilroy project would put origin-of-life studies in the vanguard of
      research. 

PMID- 25382054
TI  - The Apparent Involvement of ANMEs in Mineral Dependent Methane Oxidation, as an
      Analog for Possible Martian Methanotrophy.
AB  - On Earth, marine anaerobic methane oxidation (AOM) can be driven by the microbial
      reduction of sulfate, iron, and manganese. Here, we have further characterized
      marine sediment incubations to determine if the mineral dependent methane
      oxidation involves similar microorganisms to those found for sulfate-dependent
      methane oxidation. Through FISH and FISH-SIMS analyses using 13C and 15N labeled
      substrates, we find that the most active cells during manganese dependent AOM are
      primarily mixed and mixed-cluster aggregates of archaea and bacteria. Overall,
      our control experiment using sulfate showed two active bacterial clusters, two
      active shell aggregates, one active mixed aggregate, and an active archaeal
      sarcina, the last of which appeared to take up methane in the absence of a
      closely-associated bacterial partner. A single example of a shell aggregate
      appeared to be active in the manganese incubation, along with three mixed
      aggregates and an archaeal sarcina. These results suggest that the microorganisms
      (e.g., ANME-2) found active in the manganese-dependent incubations are likely
      capable of sulfate-dependent AOM. Similar metabolic flexibility for Martian
      methanotrophs would mean that the same microbial groups could inhabit a diverse
      set of Martian mineralogical crustal environments. The recently discovered
      seasonal Martian plumes of methane outgassing could be coupled to the reduction
      of abundant surface sulfates and extensive metal oxides, providing a feasible
      metabolism for present and past Mars. In an optimistic scenario Martian
      methanotrophy consumes much of the periodic methane released supporting on the
      order of 10,000 microbial cells per cm2 of Martian surface. Alternatively, most
      of the methane released each year could be oxidized through an abiotic process
      requiring biological methane oxidation to be more limited. If under this
      scenario, 1% of this methane flux were oxidized by biology in surface soils or in
      subsurface aquifers (prior to release), a total of about 1020 microbial cells
      could be supported through methanotrophy with the cells concentrated in regions
      of methane release. 

PMID- 25382055
TI  - Approaches to the origin of life on Earth.
AB  - I discuss briefly the history of the origin of life field, focusing on the
      "Miller" era of prebiotic synthesis, through the "Orgel" era seeking enzyme free
      template replication of single stranded RNA or similar polynucleotides, to the
      RNA world era with one of its foci on a ribozyme with the capacity to act as a
      polymerase able to copy itself. I give the history of the independent invention
      in 1971 by T. Ganti, M. Eigen and myself of three alternative theories of the
      origin of molecular replication: the Chemotron, the Hypercycle, and Collectively
      Autocatalytic Sets, CAS, respectively. To date, only collectively autocatalytic
      DNA, RNA, and peptide sets have achieved molecular reproduction of polymers.
      Theoretical work and experimental work on CAS both support their plausibility as
      models of openly evolvable protocells, if housed in dividing compartments such as
      dividing liposomes. My own further hypothesis beyond that of CAS in themselves,
      of their formation as a phase transition in complex chemical reaction systems of
      substrates, reactions and products, where the molecules in the system are
      candidates to catalyze the very same reactions, now firmly established as
      theorems, awaits experimental proof using combinatorial chemistry to make
      libraries of stochastic DNA, RNA and/or polypeptides, or other classes of
      molecules to test the hypothesis that molecular polymer reproduction has emerged
      as a true phase transition in complex chemical reaction systems. I remark that my
      colleague Marc Ballivet of the University of Geneva and I, may have issued the
      first publications discussing what became combinatorial chemistry, in published
      issued patents in 1987, 1989 and later, in this field. 

PMID- 25382057
TI  - Tyrosine kinase receptor B (TrkB) expression in colorectal cancers highlights
      anoikis resistance as a survival mechanism of tumour budding cells.
AB  - AIMS: Tumour buds in colorectal cancer represent an aggressive subgroup of non
      proliferating and non-apoptotic tumour cells. We hypothesize that the survival of
      tumour buds is dependent upon anoikis resistance. The role of tyrosine kinase
      receptor B (TrkB), a promoter of epithelial-mesenchymal transition and anoikis
      resistance, in facilitating budding was investigated. METHODS AND RESULTS:
      Tyrosine kinase receptor B immunohistochemistry was performed on a multiple-punch
      tissue microarray of 211 colorectal cancer resections. Membranous/cytoplasmic and
      nuclear expression was evaluated in tumour and buds. Tumour budding was assessed
      on corresponding whole tissue slides. Relationship to Ki-67 and caspase-3 was
      investigated. Analysis of Kirsten Ras (KRAS), proto-oncogene B-RAF (BRAF) and
      cytosine-phosphate-guanosine island methylator phenotype (CIMP) was performed.
      Membranous/cytoplasmic and nuclear TrkB were strongly, inversely correlated (P <
      0.0001; r = -0.41). Membranous/cytoplasmic TrkB was overexpressed in buds
      compared to the main tumour body (P < 0.0001), associated with larger tumours (P
      = 0.0236), high-grade budding (P = 0.0011) and KRAS mutation (P = 0.0008).
      Nuclear TrkB was absent in buds (P <0.0001) and in high-grade budding cancers (P
      =0.0073). Among patients with membranous/cytoplasmic TrkB-positive buds, high
      tumour membranous/cytoplasmic TrkB expression was a significant, independent
      adverse prognostic factor [P = 0.033; 1.79, 95% confidence interval (CI) 1.05
      3.05]. Inverse correlations between membranous/cytoplasmic TrkB and Ki-67 (r = 
      0.41; P < 0.0001) and caspase-3 (r =-0.19; P < 0.05) were observed. CONCLUSIONS:
      Membranous/cytoplasmic TrkB may promote an epithelial-mesenchymal transition
      (EMT)-like phenotype with high-grade budding and maintain viability of buds
      themselves.

PMID- 25382056
TI  - Enhanced efficacy from gene therapy in Pompe disease using coreceptor blockade.
AB  - Enzyme replacement therapy (ERT) is the standard-of-care treatment of Pompe
      disease, a lysosomal storage disorder caused by deficiency of acid alpha
      glucosidase (GAA). One limitation of ERT with recombinant human (rh) GAA is
      antibody formation against GAA. Similarly, in adeno-associated virus (AAV) vector
      mediated gene transfer for Pompe disease, development of antibodies against the
      GAA transgene product and the AAV vector prevents therapeutic efficacy and vector
      readministration, respectively. Here a nondepleting anti-CD4 monoclonal antibody
      (mAb) was administrated intravenously prior to administration of an AAV2/9 vector
      encoding GAA to suppress anti-GAA responses, leading to a substantial reduction
      of anti-GAA immunoglobulins, including IgG1, IgG2a, IgG2b, IgG2c, and IgG3.
      Transduction efficiency in liver with a subsequent AAV2/8 vector was massively
      improved by the administration of anti-CD4 mAb with the initial AAV2/9 vector,
      indicating a spread of benefit derived from control of the immune response to the
      first AAV2/9 vector. Anti-CD4 mAb along with AAV2/9-CBhGAApA significantly
      increased GAA activity in heart and skeletal muscles along with a significant
      reduction of glycogen accumulation. Taken together, these data demonstrated that
      the addition of nondepleting anti-CD4 mAb with gene therapy controls humoral
      immune responses to both vector and transgene, resulting in clear therapeutic
      benefit in mice with Pompe disease. 

PMID- 25382060
TI  - Microsecond folding and domain motions of a spider silk protein structural
      switch.
AB  - Web spiders rapidly assemble protein monomers, so-called spidroins, into
      extraordinarily tough silk fibers. The process involves the pH-triggered self
      association of the spidroin N-terminal domain (NTD), which contains a structural
      switch connecting spidroins to supermolecules. Single-molecule spectroscopy can
      detect conformational heterogeneity that is hidden to conventional methods, but
      motions of the NTD are beyond the resolution limit. Here, we engineered probes
      for 1 nm conformational changes based on the phenomenon of fluorescence quenching
      by photoinduced electron transfer into the isolated NTD of a spidroin from the
      nursery web spider Euprosthenops australis. Correlation analysis of single
      molecule fluorescence fluctuations uncovered site-dependent nanosecond-to
      microsecond movement of secondary and tertiary structure. Kinetic amplitudes were
      most pronounced for helices that are part of the association interface and where
      structural studies show large displacements between monomeric and dimeric
      conformations. A single tryptophan at the center of the five-helix bundle toggled
      conformations in ~100 MUs and in a pH-dependent manner. Equilibrium denaturation
      and temperature-jump relaxation experiments revealed cooperative and ultrafast
      folding in only 60 MUs. We deduced a free-energy surface that exhibits native
      state ruggedness with apparently similar barrier heights to folding and native
      motions. Observed equilibrium dynamics within the domain suggest a conformational
      selection mechanism in the rapid association of spidroins through their NTDs
      during silk synthesis by web spiders.

PMID- 25382058
TI  - Development of a receptor-targeted gene delivery system using CXCR4 ligand
      conjugated cross-linking peptides.
AB  - BACKGROUND: Success in gene therapy greatly depends on the efficiency of nucleic
      acid delivery. Important features of the carriers for gene delivery should
      include an enhanced transfection ability, targeting of specific receptors and low
      toxicity. In the present study, we characterized CXCR4-targeted cross-linking
      peptides modified with an N-terminal fragment of chemokine stromal cell-derived
      factor-1alpha as carriers for gene delivery. METHODS: We studied three variants
      of DNA/carrier complexes with different targeting ligand content. The
      physicochemical characteristics of the complexes, including their DNA-binding and
      protective ability, interaction with glycosaminoglycans and size, were
      determined. Transfection efficacy was studied in cell lines with different levels
      of CXCR4 expression (HeLa, A172, CHO, E.A.hy926) and also in human mesenchymal
      stem cells (hMSCs). The influence of the ligand content on the efficacy of
      transfection was studied by means of chlorpromazine blockage of clathrin-mediated
      endocytosis, competition with CXCR4-antagonist AMD3100, and valproic acid
      treatment of hMSCs. RESULTS: CXCR4-targeted peptides were evaluated for their
      physicochemical properties and in vitro transfection capacities. Ligand-modified
      carriers were found to be 10- to 50-fold more effective than unmodified carriers
      in CXCR4-positive cells. By contrast, their transfection efficacy in CXCR4
      negative cells was similar to unmodified carriers. Experiments with
      chlorpromazine demonstrated receptor-specific transfection in A172 cells. The
      transfection efficacy of CXCR4-targeted carriers in AMD3100-treated HeLa cells
      was reduced by two-fold compared to the untreated control. Valproic acid
      treatment resulted in a four- to 15-fold increase of transfection efficacy for
      ligand-modified carriers in hMSCs. CONCLUSIONS: CXCR4-targeted cross-linking
      peptides should be considered as useful tools for nonviral gene delivery into
      tumor and mesenchymal stem cells.

PMID- 25382061
TI  - Attachment models in incarcerated sex offenders: a preliminary Italian study
      using the adult attachment interview.
AB  - A group of sex offenders (clinical group: n = 19) was compared to a nonclinical
      sample matched by age, years of education, and gender (control group A: n = 19)
      to verify a higher incidence of insecure attachment models among sex offenders.
      In addition, we tested whether sex offenders were characterized by specific
      childhood experiences, compared to control adults (control group B: n = 19) with
      the same secure/insecure attachment classification. Results showed significant
      differences between offenders and control adults on both the AAI continuous score
      and the distribution of the two-way attachment classifications. Furthermore, sex
      offenders reported more intense experiences of rejection by the father figure and
      abuse in the family context during early childhood compared to not offenders
      subjects with the same attachment classification.

PMID- 25382063
TI  - Gender equality, issue contents and publication ethics.

PMID- 25382062
TI  - Impacts of CLA and dietary concentrate proportion on blood metabolite
      concentration and proliferation of peripheral blood mononuclear cells of
      periparturient dairy cows.
AB  - The study aimed to examine effects of supplemented CLA to periparturient dairy
      cows receiving different concentrate proportions antepartum (a.p.) to investigate
      CLA effects on metabolism and immune function. Compared with adapted feeding,
      high-concentrate diet a.p. should induce a ketogenic metabolic situation
      postpartum (p.p.) to better understand how CLA works. A total of 64 pregnant
      German Holstein cows had ad libitum access to partial mixed rations based on
      concentrate and roughage 3 weeks before calving until day 60 p.p. A.p., cows
      received 100 g/day control fat (CON) or a CLA supplement, either in a low
      concentrate (20%, CON-20, CLA-20) or high-concentrate diet (60%, CON-60, CLA-60).
      P.p., concentrate proportion was adjusted to 50% while fat supplementation
      continued. After day 32 p.p., half of the animals of CLA-groups changed to CON
      supplementation (CLA-20-CON, CLA-60-CON). A ketogenic metabolic state p.p. was
      not achieved and respective impacts of CLA could not be examined. Blood samples
      for isolation of peripheral blood mononuclear cells (PBMC) were collected on day 
      21, 7, 28 and 56 relative to calving. Blood chemistry samples were taken over the
      entire experimental period. Mitogen-stimulated proliferation of PBMC remained
      unaffected. Besides serum concentrations of triglycerides, total bilirubin, total
      protein, albumin and IGF-1, clinical-chemical serum characteristics remained
      uninfluenced by treatments. No post-supplementation effect could be observed.
      Measured blood metabolites and mitogen-stimulated proliferation of PBMC indicate
      that all groups had an increased metabolic stress around calving, whereby group
      CLA-20 was affected more severely. Overall, supplemented CLA did not positively
      affect metabolism or immune function of periparturient dairy cows. However,
      feeding CLA in a low-concentrate diet a.p. seems to increase liver stress around
      calving via reduced DMI. 

PMID- 25382064
TI  - Case series of rash associated with influenza B in school children.
AB  - This case series describes morbilliform and other rash presentations among
      schoolchildren during a March 2014 outbreak of influenza-like illness (ILI) in
      British Columbia, Canada. Multiplex nucleic acid testing of nasopharyngeal
      specimens and paired serologic investigations identified that influenza B,
      characterized as B/Massachusetts/02/2012-like (Yamagata-lineage), was the only
      viral aetiology and most likely cause of ILI and rash. An association between
      influenza B and rash has been described infrequently elsewhere, and not
      previously in North America. Influenza B should be considered in the differential
      diagnosis of febrile exanthem. Evaluation of the nature, incidence and
      contributing agent-host-environment interactions, and immunologic mechanisms to
      possibly explain influenza-associated rash is warranted. 

PMID- 25382065
TI  - The zigzag model of plant-microbe interactions: is it time to move on?

PMID- 25382066
TI  - Potential risk factors of re-intervention after endovascular repair for type B
      aortic dissections.
AB  - OBJECTIVES: To assess the potential risk factors of re-intervention after
      thoracic endovascular aortic repair (TEVAR). BACKGROUND: TEVAR has been chosen as
      a less invasive alternative for Type B aortic dissections (TBADs); however, the
      potential risk factors of re-intervention remain unclear. METHODS: A total of 252
      TBADs patients initially treated with TEVAR between September 1998 and July 2012
      were retrospectively reviewed. The indications for the initial TEVAR were 32
      aorta enlargement (24 chronic), 71 malperfusion, 46 rupture (32 chronic), 67
      refractory pain (54 chronic), and 44 refractory hypertension (38 chronic). The
      patients were stratified into single-intervention group and multi-intervention
      group. RESULTS: The mean age was 54.1 years with 81.7% of male. We found the time
      from symptom onset to TEVAR was longer in multi-intervention group (17 vs. 112.5
      days, P = 0.006). Higher proportions of chronic dissection and smoking occurred
      in multi-intervention group (53.9% vs. 79.2% and 43.9% vs. 70.8%, P = 0.018 and
      0.012, respectively). The differences of oversizing, operation time, contrast
      medium dose, and blood loss between the groups were significant (13.8 +/- 2.4%
      vs. 16.4 +/- 2.9%, 92.5 vs. 196 minutes, 110 vs. 210 ml, 100 vs. 300 ml; P <
      0.001, <0.001, =0.002, and =0.003, respectively). The mortality within 30 days
      was 2.4% and the rates of stoke, paraplegia and retrograde dissection were 3.6%,
      5.6% and 0.8%, respectively. The most common reasons of re-intervention were
      endoleaks, new dissections and incomplete thrombosis of the false lumen.
      CONCLUSIONS: we concluded that chronic phase, smoking and too big oversizing were
      potential risk factors of re-intervention.

PMID- 25382067
TI  - Response to MAPK pathway inhibitors in BRAF V600M-mutated metastatic melanoma.
AB  - WHAT IS KNOWN AND OBJECTIVE: The management of metastatic melanoma has changed
      significantly in the past decade with the development of immunotherapies and
      targeted molecular therapies. Trials of targeted therapies have focused mainly on
      patients with the most common BRAF V600 mutations, namely V600E/K substitutions,
      with very little information available on the benefit of targeted therapies on
      less commonly occurring mutations such as V600R/D and M. CASE SUMMARY: We present
      a 54-year-old man with metastatic melanoma harbouring a rare BRAF V600M mutation,
      who experienced clinical and radiological response to combined therapy with the
      BRAF inhibitor dabrafenib and MEK inhibitor trametinib. WHAT IS NEW AND
      CONCLUSION: As our understanding of these therapies evolves and an increasing
      number of patients have mutational testing performed, there is a clear imperative
      -as highlighted by this case--to test for rarer mutations and facilitate their
      inclusion both in everyday practice and in future clinical trials.

PMID- 25382068
TI  - Hair follicle targeting, penetration enhancement and Langerhans cell activation
      make cyanoacrylate skin surface stripping a promising delivery technique for
      transcutaneous immunization with large molecules and particle-based vaccines.
AB  - Transcutaneous immunization (TCI) requires targeting of a maximum number of skin
      antigen-presenting cells as non-invasive as possible on small skin areas. In two
      clinical trials, we introduced cyanoacrylate skin surface stripping (CSSS) as a
      safe method for TCI. Here, using ex vivo human skin, we demonstrate that one CSSS
      procedure removed only 30% of stratum corneum, but significantly increased the
      penetration of 200 nm polystyrene particles deep into vellus and intermediate
      hair follicles from where they could not been retrieved by conventional tape
      stripping. Two subsequent CSSS had no striking additional effect. CSSS increased
      particle penetration in superficial stratum corneum and induced Langerhans cell
      activation. Formulation in amphiphilic ointment or massage did not substantially
      influences the interfollicular penetration profiles. Hair follicle (HF) targeting
      by CSSS could become a highly effective tool for TCI when combined with carrier
      based delivery and is gaining new attention as our understanding on the HF immune
      system increases. 

PMID- 25382070
TI  - Incidence and clinical presentation of primary hemophagocytic lymphohistiocytosis
      in Sweden.
AB  - BACKGROUND: Primary hemophagocytic lymphohistiocytosis (HLH) represents a group
      of inherited hyperinflammatory immunodeficiencies, including familial HLH (FHL),
      Griscelli syndrome type 2 (GS2), and X-linked lymphoproliferative syndrome (XLP).
      We previously reported an annual incidence of suspected primary HLH in Sweden
      1971-1986 of 0.12 per 100,000 children. Here, we determined if the incidence had
      increased with concomitant awareness. PROCEDURE: Children <15 years old
      presenting with HLH 1987-2006 in Sweden were identified through the national
      mortality registry as well as by nation-wide inquiries to all pediatric centers.
      HLH was diagnosed according to the HLH-2004 diagnostic guidelines (in case of
      missing data of at least three of the eight diagnostic criteria, fulfillment of
      four was sufficient for inclusion). We defined primary HLH as patients presenting
      with HLH requiring transplantation or dying of disease. RESULTS: Remarkably, the
      minimal annual incidence rate of primary HLH remained 0.12 per 100,000 children,
      equating to 1.8 per 100,000 live births. Notably, an increased overall survival
      was observed in 1997-2006, relative to the period 1987-1996. During the
      subsequent 5-year period, 2007-2011, the incidence of genetically and/or
      functionally verified primary HLH was 0.15 per 100,000 children per year,
      suggesting that new assays may aid the identification of patients with primary
      HLH. CONCLUSION: The annual incidence of primary HLH in Sweden is 0.12-0.15 per
      100,000 children per year. Pediatr Blood Cancer 2015;62:346-352. (c) 2014 Wiley
      Periodicals, Inc.

PMID- 25382069
TI  - Amyotrophic lateral sclerosis onset is influenced by the burden of rare variants
      in known amyotrophic lateral sclerosis genes.
AB  - OBJECTIVE: To define the genetic landscape of amyotrophic lateral sclerosis (ALS)
      and assess the contribution of possible oligogenic inheritance, we aimed to
      comprehensively sequence 17 known ALS genes in 391 ALS patients from the United
      States. METHODS: Targeted pooled-sample sequencing was used to identify variants
      in 17 ALS genes. Fragment size analysis was used to define ATXN2 and C9ORF72
      expansion sizes. Genotype-phenotype correlations were made with individual
      variants and total burden of variants. Rare variant associations for risk of ALS
      were investigated at both the single variant and gene level. RESULTS: A total of
      64.3% of familial and 27.8% of sporadic subjects carried potentially pathogenic
      novel or rare coding variants identified by sequencing or an expanded repeat in
      C9ORF72 or ATXN2; 3.8% of subjects had variants in >1 ALS gene, and these
      individuals had disease onset 10 years earlier (p = 0.0046) than subjects with
      variants in a single gene. The number of potentially pathogenic coding variants
      did not influence disease duration or site of onset. INTERPRETATION: Rare and
      potentially pathogenic variants in known ALS genes are present in >25% of
      apparently sporadic and 64% of familial patients, significantly higher than
      previous reports using less comprehensive sequencing approaches. A significant
      number of subjects carried variants in >1 gene, which influenced the age of
      symptom onset and supports oligogenic inheritance as relevant to disease
      pathogenesis.

PMID- 25382071
TI  - Characterizing spatial uncertainty when integrating social data in conservation
      planning.
AB  - Recent conservation planning studies have presented approaches for integrating
      spatially referenced social (SRS) data with a view to improving the feasibility
      of conservation action. We reviewed the growing conservation literature on SRS
      data, focusing on elicited or stated preferences derived through social survey
      methods such as choice experiments and public participation geographic
      information systems. Elicited SRS data includes the spatial distribution of
      willingness to sell, willingness to pay, willingness to act, and assessments of
      social and cultural values. We developed a typology for assessing elicited SRS
      data uncertainty which describes how social survey uncertainty propagates when
      projected spatially and the importance of accounting for spatial uncertainty such
      as scale effects and data quality. These uncertainties will propagate when
      elicited SRS data is integrated with biophysical data for conservation planning
      and may have important consequences for assessing the feasibility of conservation
      actions. To explore this issue further, we conducted a systematic review of the
      elicited SRS data literature. We found that social survey uncertainty was
      commonly tested for, but that these uncertainties were ignored when projected
      spatially. Based on these results we developed a framework which will help
      researchers and practitioners estimate social survey uncertainty and use these
      quantitative estimates to systematically address uncertainty within an analysis.
      This is important when using SRS data in conservation applications because
      decisions need to be made irrespective of data quality and well characterized
      uncertainty can be incorporated into decision theoretic approaches. 

PMID- 25382072
TI  - High-efficiency, solution-processed, multilayer phosphorescent organic light
      emitting diodes with a copper thiocyanate hole-injection/hole-transport layer.
AB  - Copper thiocyanate (CuSCN) is introduced as a hole-injection/hole-transport layer
      (HIL/HTL) for solution-processed organic light-emitting diodes (OLEDs). The OLED
      devices reported here with CuSCN as HIL/HTL perform significantly better than
      equivalent devices fabricated with a PEDOT:PSS HIL/HTL, and solution-processed,
      phosphorescent, small-molecule, green OLEDs with maximum luminance >=10 000 cd m(
      2) , maximum luminous efficiency <=50 cd A(-1) , and maximum luminous power
      efficiency <=55 lm W(-1) are demonstrated. 

PMID- 25382073
TI  - Water-soluble molecularly imprinted nanoparticles (MINPs) with tailored,
      functionalized, modifiable binding pockets.
AB  - Construction of receptors with binding sites of specific size, shape, and
      functional groups is important to both chemistry and biology. Covalent imprinting
      of a photocleavable template within surface-core doubly cross-linked micelles
      yielded carboxylic acid-containing hydrophobic pockets within the water-soluble
      molecularly imprinted nanoparticles. The functionalized binding pockets were
      characterized by their binding of amine- and acid-functionalized guests under
      different pH values. The nanoparticles, on average, contained one binding site
      per particle and displayed highly selective binding among structural analogues.
      The binding sites could be modified further by covalent chemistry to modulate
      their binding properties. 

PMID- 25382075
TI  - Congenital absence of pericardium: a nomad heart.
AB  - Congenital pericardial absence is a rare cardiac defect. Although most patients
      are asymptomatic, recognising this condition is clinically important as it can
      cause serious complications. We report the case of an asymptomatic 33-year-old
      woman seeking medical attention due to a family history of sudden cardiac death.
      The investigation led us to the diagnosis of congenital absence of the
      pericardium. The role of imaging in the diagnosis of this rare cardiac
      malformation is briefly discussed. 

PMID- 25382074
TI  - Subthreshold grid laser versus intravitreal bevacizumab as second-line therapy
      for macular edema in branch retinal vein occlusion recurring after conventional
      grid laser treatment.
AB  - PURPOSE: To compare the effects of subthreshold grid laser treatment (SGLT) and
      intravitreal bevacizumab injection (IVBI) for the treatment of macular edema (ME)
      secondary to branch retinal vein occlusion (BRVO) recurring after conventional
      grid laser photocoagulation. METHODS: Thirty-five eyes were considered in this
      prospective, randomised, interventional study and treated with micropulse diode
      laser (SGLT subgroup) or IVBI (IVBI subgroup). SGLT was administered once,
      whereas IVBI (1.25 mg) was given at baseline and then on a pro re nata regimen
      according to ME presence on optical coherence tomography (OCT), performed at
      monthly examinations over a 12-month follow-up. Primary outcome measures were the
      mean BCVA changes over the follow-up and the decrease in mean central foveal
      thickness (CFT) on optical coherence tomography (OCT). Secondary outcomes
      included the proportion of eyes that gained at least 15 letters (approximately
      three lines) at the 12-month examination. RESULTS: Eighteen and 17 patients were
      assigned to SGLT and IVBI subgroups, respectively. At baseline, the subgroups
      were similar with regard to mean ME duration, BCVA, and CFT. At month 12, mean
      CFT significantly improved from 484 MUm to 271 MUm in the IVBI subgroup, whereas
      it was unchanged in the SGLT subgroup. Mean BCVA changed from 0.92 +/- 0.3
      (LogMAR) to 0.99 +/- 0.2 in the SGLT subgroup; in the IVBI subgroup, mean BCVA
      showed a statistically significant improvement from 0.94 +/- 0.3 to 0.72 +/- 0.2.
      Ten patients in the IVBI subgroup (58 %) and no patient in the SGLT subgroup
      gained at least three lines. CONCLUSION: At the 1-year follow-up, IVBI provided a
      significant functional and anatomical improvement, whereas SGLT failed to
      demonstrate any beneficial effects. IVBI might be a useful approach in the
      treatment of recurrent ME secondary to BRVO already treated with conventional
      grid laser photocoagulation. UMIN registry, number UMIN000005014, URL:
      http://www.umin.ac.jp/ctr/index.htm.

PMID- 25382076
TI  - The weekend effect and compassion fatigue.

PMID- 25382077
TI  - Will the NHS find time for mental health nursing?

PMID- 25382078
TI  - Atopic eczema: the current state of clinical research.
AB  - Atopic eczema (AE), also known as atopic dermatitis, is a chronic, inflammatory,
      itchy skin condition that usually develops in early childhood. There has been a
      steep rise in the burden of atopic eczema, with up to 20% of children in
      developed countries now suffering from the disease (Flohr and Mann, 2014).
      Although atopic eczema is not always recognised as a serious medical condition by
      health professionals, it can have a significant negative impact on quality of
      life for children and their parents or carers (National Institute for Health and
      Care Excellence (NICE), 2013). The application of eczema treatments often results
      in conflict between parents and their children, which affects family
      relationships further and drains the carers' physical and emotional resources
      (Santer et al, 2013). It is typically an episodic disease of exacerbation with
      flares occurring two or three times per month, with periods of remission. For
      some children, however, it is continuous (NICE, 2013). Although a common
      condition, there are uncertainties regarding treatments used both for health
      professionals and for patients and their carers. A recent priority setting
      partnership highlighted the top 14 uncertainties (Box 1), which will provide
      guidance for future research and answer questions that are important to both
      clinicians and patients (Batchelor et al, 2013). This article cannot cover all
      aspects of AE, but will give an update on some of the current research projects
      and signpost the reader to further resources.

PMID- 25382079
TI  - Glasgow Coma Scale flow chart: a beginner's guide.
AB  - The Glasgow Coma Scale (GCS) has been accepted nationally and internationally as
      a tool to assess depth and duration of consciousness since it was published in
      1974. Although it was intended to be an easy and practical bedside tool for any
      grade of health professional, it is considered to be ambiguous and confusing for
      infrequent users. Moreover, there has been increasing concern about the accuracy
      and effectiveness of the GCS observation carried out by these users, which could
      result from lack of training and dissemination of benchmarking across non
      specialist areas. This paper aims to introduce a GCS flow chart to guide users
      step by step when assessing a patient's level of consciousness. 

PMID- 25382080
TI  - Haematuria: classification, causes and investigations.
AB  - The majority of patients who attend haematuria clinics for investigation of blood
      in their urine will be found to have either no cause or a benign cause. Between
      20% and 25% of people with visible blood in their urine and 5-10% of people with
      non-visible blood in their urine will be diagnosed with a urological malignancy,
      i.e. bladder, kidney or prostate cancer. Haematuria is therefore a significant
      symptom that should be investigated promptly and thoroughly to exclude cancer as
      quickly as possible. This article gives an overview of the causes of haematuria
      and the investigations that patients will undergo when referred to a haematuria
      clinic. 

PMID- 25382081
TI  - Challenges in tuberculosis management in Peru and England.
AB  - Tuberculosis (TB) is a serious but preventable and largely treatable disease
      caused by the bacterium Mycobacterium tuberculosis. Although there is evidence
      that the UK incidence remains stable, rates of the disease, particularly in some
      London boroughs, remain high, earning it the unenviable title of the
      'tuberculosis capital of Europe'. In March 2014 Public Health England published a
      consultation document on a collaborative strategy for tackling tuberculosis in
      England. This highlights a growing concern surrounding the issue. In the 1990s,
      Peru's tuberculosis epidemic saw the country listed among the Pan-American Health
      Organisation's top 23 countries of heaviest burden. Since then overall rates,
      although remaining significantly higher than those of the UK, have fallen
      dramatically. This article uses the observations of a BSc Nursing student
      undertaking an international elective in Peru to highlight some of the challenges
      faced by nurses in managing TB and draws parallels with those faced in the UK. 

PMID- 25382082
TI  - The NHS end-of-term report.
AB  - John Tingle discusses the Care Quality Commission's fifth annual report on the
      state of health and care in the NHS. 

PMID- 25382083
TI  - The better care fund.

PMID- 25382084
TI  - Should the influenza vaccine be mandatory for frontline staff?
AB  - Professor Alan Glasper from the University of Southampton discusses the latest
      flu plan initiative by the Department of Health, NHS England and Public Health
      England for the winter of 2014-15 designed to increase flu vaccine uptake among
      frontline health professionals. 

PMID- 25382085
TI  - Mental capacity and mental health acts part 4: a new framework.
AB  - The increasingly complex interface between the Mental Health Act 1983 and the
      Mental Capacity Act 2005 has been discussed in this column over the last three
      months. The boundaries between the two statutes is becoming increasingly blurred
      with the Court of Protection, a specialist court that considers cases about
      people lacking decision-making capacity, commonly being asked to make decisions
      on mental health law as well. Northern Ireland is proposing to resolve the
      interface problem by repealing its mental health laws and replacing them with a
      single statutory framework for mental capacity law. If passed, it will give all
      adults with capacity the right to consent to or refuse any form of treatment.
      Physical and mental conditions will be on an equal footing and there would be no
      compulsory detention or treatment of adults with capacity. For those whose lack
      capacity, treatment will be available in their best interests with arrangements
      in place to authorise situations where the care arrangements amount to a
      deprivation of liberty. In this article Richard Griffith considers the new
      proposals for Northern Ireland and wonders where these proposals point the way
      for the other devolved nations to develop their mental health and mental capacity
      law for a 21st century Britain. 

PMID- 25382086
TI  - Written communication: from staff nurse to nurse consultant. Part 6: reflective
      writing.

PMID- 25382087
TI  - The nursing voice must be heard.

PMID- 25382088
TI  - Fructose-coated nanoparticles: a promising drug nanocarrier for triple-negative
      breast cancer therapy.
AB  - Fructose transporter GLUT5 is overexpressed in breast cancer cell lines, but not
      in healthy tissue. Micelles based on fructose, which were found to be low
      fouling, showed a high uptake by breast cancer cells (MCF-7 and MDA-MB-231
      cells), but only negligible uptake by macrophages. 

PMID- 25382089
TI  - Prevalence and complications of trauma to the primary dentition in a
      subpopulation of Spanish children in southern Europe.
AB  - BACKGROUND: During the first years of life, when children begin to walk and
      socialize, they are particularly vulnerable to traumatic injuries to the primary
      teeth; indeed, after dental caries, such injuries are the second most frequent
      cause of pediatric dental consultation. Nonetheless, the reported prevalence of
      trauma to the primary teeth varies depending on the literature source, type of
      injury, the patient's age, and the most common associated complications. AIM: To
      analyze new epidemiological data and complications associated with traumatic
      injuries to the primary teeth of Spanish children. MATERIAL AND METHODS: A
      retrospective study was carried out in a subpopulation of 879 Spanish children in
      southern Europe aged between one and 7 years old, with primary and early mixed
      dentition. Clinical and radiological records were obtained from all pediatric
      patients who presented trauma to the primary teeth, with a follow-up period of 3
      5 years. RESULTS: A total of 21.72% of children examined had some kind of dental
      trauma and the most common age range for injuries to the primary teeth was 1-3
      years old. The most common injuries in deciduous teeth were subluxation (47.29%
      of injuries affected the periodontal ligament), intrusion (23.15%), and avulsion
      (13.63%). On the other hand, comparatively more complications were recorded as a
      result of intrusion (32 of 47 intruded teeth). CONCLUSIONS: In this Spanish
      subpopulation, a pediatric dental consultation as a result of traumatic dental
      injuries in primary dentition is most frequent in 1- and 2-year-olds, and
      subluxation is the commonest injury in the primary dentition. In turn, intrusion
      is associated with an increased frequency of complications in both the deciduous
      and the permanent teeth.

PMID- 25382090
TI  - Development and validation of a professionalism assessment scale for medical
      students.
AB  - OBJECTIVE: To develop and validate a scale for the assessment of professionalism
      in medical students based on students' perceptions of and attitudes towards
      professionalism in medicine. METHODS: This was a mixed methods study with
      undergraduate medical students. Two focus groups were carried out with 12
      students, followed by a transcript analysis (grounded theory method with open
      coding). Then, a 3-round Delphi with 20 family medicine experts was carried out.
      A psychometric assessment of the scale was performed with a group of 449
      students. The items of the Professionalism Assessment Scale could be answered on
      a five-point Likert scale. RESULTS: After the focus groups, the first version of
      the PAS consisted of 56 items and after the Delphi study, 30 items remained. The
      final sample for quantitative study consisted of 122 students (27.2% response
      rate). There were 95 (77.9%) female students in the sample. The mean age of the
      sample was 22.1 +/- 2.1 years. After the principal component analysis, we removed
      8 items and produced the final version of the PAS (22 items). The Cronbach's
      alpha of the scale was 0.88. Factor analysis revealed three factors: empathy and
      humanism, professional relationships and development and responsibility.
      CONCLUSIONS: The new Professionalism Assessment Scale proved to be valid and
      reliable. It can be used for the assessment of professionalism in undergraduate
      medical students.

PMID- 25382091
TI  - Penetration of topical chloramphenicol into the anterior chamber.

PMID- 25382092
TI  - Hormonal evidence of selection in utero revisited.
AB  - OBJECTIVES: Human conception cohorts in gestation during stressful times
      reportedly yield lower ratios of male to female live births than do other
      conception cohorts. Much literature attributes this phenomenon to spontaneous
      abortion of less fit male fetuses. Controversy remains, however, as to whether
      stressful times make males fetuses less fit ("Shifting Distribution" of fitness)
      or whether male fetuses need greater fitness to avoid spontaneous abortion during
      stressful times ("Shifting Criterion" for survival). METHODS: Although research
      using gestational hCG as a signal of fetal fitness reports support for the latter
      mechanism, we believe an analytic error casts doubt on those findings. Here we
      offered an alternative test that corrects the error. CONCLUSION: This more
      accurate test found similar results to those originally reported.

PMID- 25382093
TI  - Unprecedented silicon(II)->calcium complexes with N-heterocyclic silylenes.
AB  - The first N-heterocyclic silylene (NHSi) complexes of any s-block element to date
      are reported for calcium: [(eta(5)-C5Me5)2Ca<-:Si(O-C6H4-2-(t)Bu){(N(t)Bu)2CPh}]
      (6) and [(eta(5)-C5Me5)2Ca<-:Si(N(t)BuCH)2] (7). Complexes 6 and 7 are isolable
      in a facile way upon reaction of the corresponding free N-heterocyclic silylenes
      (NHSis) with [(eta(5)-C5Me5)2Ca] (2). Complexes 6 and 7 were fully characterised
      by spectroscopic means and the single crystal X-ray diffraction analysis of 6 is
      also reported. Analysis of the bonding situation by DFT methods including a Bader
      Atoms in molecules (AIM) analysis is also reported. The bonding interaction
      between the Si and Ca centres in complexes 6 and 7 can best be viewed as sigma
      donor-acceptor interactions, with a considerable ionic contribution in the bond.
      The reactivity towards the oxygen containing substrates THF and benzophenone is
      also discussed.

PMID- 25382094
TI  - Mapping the pathways to eye care in a rural south-east Nigerian population: any
      implications for practice, eye care programs and policy?
AB  - INTRODUCTION: The appropriateness of the initial pathway to care, especially eye
      care, is critical for timeliness and outcomes of care. Individual-dependent and
      health system-determined factors influence the preferred initial pathway to care.
      This study aimed to map the initial pathways to eye care in a rural population in
      south-east Nigeria and identify the associated factors. METHODS: This study was a
      population-based, cross-sectional descriptive survey conducted in Abagana, a
      rural south-east Nigeria community, in September 2011. Using a researcher
      administered questionnaire, data on participants' sociodemographics, preferred
      initial eyecare pathway when confronted with an eye disorder and their reason(s)
      for the choice of pathway were collected. Descriptive and analytical statistics
      were performed. Regression analysis was used to identify independent predictors
      of visiting an ophthalmologist when confronted with an eye disorder. In all
      comparisons, p < 0.05 was considered statistically significant. RESULTS: The
      participants (n = 501: 263 men; 238 women) were aged 48.9+/-16.3 years (range 18
      93 years). The majority of the participants were married (339; 67.7%) and
      possessed formal education (415; 82.8%). The participants' frequently preferred
      initial pathways to eye care were to consult a patent medicine dealer (178;
      35.0%), to consult an ophthalmologist (165; 33.0%), and to self-medicate (125;
      25.0%). Possession of formal education (odds ratio 0.3; 95% confidence interval
      0.1-0.5; p < 0.001) was the only significant sociodemographic predictor of
      consulting an ophthalmologist when confronted with an eye disorder The
      participants' main reasons for not consulting an ophthalmologist were ignorance
      (190; 56.5%), cost (199; 59.2%), and restricted spatial access (228; 67.9%).
      CONCLUSIONS: The majority of the respondents chose an inappropriate eyecare
      pathway in the event of an eye disorder. The reported barriers to appropriate
      pathway selection are amenable to community-based eye health education, enhanced
      affordability, and even distribution of eyecare services. Integrating other
      alternative care pathways into orthodox eye care should be considered.

PMID- 25382095
TI  - Basic science and the Ebola virus infection epidemic.

PMID- 25382097
TI  - Reaction mechanisms of aqueous monoethanolamine with carbon dioxide: a combined
      quantum chemical and molecular dynamics study.
AB  - Aqueous monoethanolamine (MEA) has been extensively studied as a solvent for CO2
      capture, yet the underlying reaction mechanisms are still not fully understood.
      Combined ab initio and classical molecular dynamics simulations were performed to
      revisit and identify key elementary reactions and intermediates in 25-30 wt%
      aqueous MEA with CO2, by explicitly taking into account the structural and
      dynamic effects. Using static quantum chemical calculations, we also analyzed in
      more detail the fundamental interactions involved in the MEA-CO2 reaction. We
      find that both the CO2 capture by MEA and solvent regeneration follow a
      zwitterion-mediated two-step mechanism; from the zwitterionic intermediate, the
      relative probability between deprotonation (carbamate formation) and CO2 removal
      (MEA regeneration) tends to be determined largely by the interaction between the
      zwitterion and neighboring H2O molecules. In addition, our calculations clearly
      demonstrate that proton transfer in the MEA-CO2-H2O solution primarily occurs
      through H-bonded water bridges, and thus the availability and arrangement of H2O
      molecules also directly impacts the protonation and/or deprotonation of MEA and
      its derivatives. This improved understanding should contribute to developing more
      comprehensive kinetic models for use in modeling and optimizing the CO2 capture
      process. Moreover, this work highlights the importance of a detailed atomic-level
      description of the solution structure and dynamics in order to better understand
      molecular mechanisms underlying the reaction of CO2 with aqueous amines. 

PMID- 25382096
TI  - GLP-1 receptor agonists for type 2 diabetes mellitus: recent developments and
      emerging agents.
AB  - More than 26 million people in the United States have type 2 diabetes mellitus
      (T2D). Many treatment options exist, but achieving long-term glycemic control in
      patients with T2D remains challenging. The glucagon-like peptide-1 receptor
      agonists (GLP-1 RAs) offer a treatment option that improves glycemic control and
      reduces weight, with a low risk of hypoglycemia. They have emerged as attractive
      options for the treatment of T2D, and significant advances and developments
      continue to be published regarding these agents. To identify relevant literature
      on emerging issues related to GLP-1 RAs, a search of the MEDLINE database was
      performed. Studies published in English evaluating the safety and efficacy of GLP
      1 RAs were analyzed. Because of their advantages and unique mechanism of action,
      GLP-1 RAs are currently being studied in new clinical areas, including in
      combination with basal insulin, as adjunctive therapy in type 1 diabetes, and for
      weight loss. In addition, there are several emerging agents in development.
      Lixisenatide is a once-daily GLP-1 RA that targets postprandial glucose and may
      be most useful when added to basal insulin as an alternative to rapid-acting
      insulin. Albiglutide and dulaglutide are once-weekly GLP-1 RAs that may offer
      more convenient dosing. The most common adverse effects of all GLP-1 RA agents
      are gastrointestinal (e.g., nausea, diarrhea, and vomiting), but the rates of
      occurrence vary among agents. Due to the differences in pharmacokinetics,
      efficacy, rates of adverse effects, and administration requirements within the
      GLP-1 RA class, each agent should be evaluated independently. The future of GLP-1
      RAs offers broader treatment options for T2D as well as potential in other
      treatment areas. 

PMID- 25382098
TI  - Pathology and Virus Distribution in the Lung and Lymphoid Tissues of Pigs
      Experimentally Inoculated with Three Distinct Type 1 PRRS Virus Isolates of
      Varying Pathogenicity.
AB  - Porcine reproductive and respiratory syndrome (PRRS) continues to be the most
      economically important disease of swine worldwide. The appearance of highly
      pathogenic PRRS virus (PRRSV) strains in Europe and Asia has raised concerns
      about this disease and initiated increased efforts to understand the
      pathogenesis. In this study, we have compared the pathology and the virus
      distribution in tissues of pigs experimentally inoculated with three different
      genotype 1 PRRSV isolates. Sixty 5-week-old pigs were inoculated intranasally
      with a) the Lelystad virus (LV), b) a field strain from the UK causing
      respiratory clinical signs (UK) or c) a highly pathogenic strain from Belarus
      (BE). Sixteen animals were mock-infected and used as controls. The animals were
      euthanized at 3, 7 and 35 days post-infection (dpi), and lung and lymphoid
      tissues collected for histopathological examination and PRRSV detection by
      immunohistochemistry (IHC). Histopathological lesions consisted of interstitial
      pneumonia with mononuclear cell infiltrates in the lungs, lymphoid depletion,
      apoptosis and follicular hyperplasia in the spleen, lymph nodes and tonsil and
      lymphoid depletion in the thymus. Porcine reproductive and respiratory syndrome
      virus was detected mainly in monocytes-macrophages. BE-infected animals showed
      the highest pathological scores and the highest presence of virus at 3 and 7 dpi,
      followed by the UK field strain and then LV. Moderate lesions were observed at 35
      dpi with lesser detection of PRRSV by IHC in each infected group. The highly
      pathogenic BE strain induced more severe pathology in both lungs and lymphoid
      organs of pigs compared with the classic field isolate and the prototype LV. The
      increased severity of pathology was in correlation with the presence of a higher
      number of PRRSV-infected cells in the tissues.

PMID- 25382099
TI  - Resonant Raman spectroscopy of twisted multilayer graphene.
AB  - Graphene and other two-dimensional crystals can be combined to form various
      hybrids and heterostructures, creating materials on demand with properties
      determined by the interlayer interaction. This is the case even for a single
      material, where multilayer stacks with different relative orientation have
      different optical and electronic properties. Probing and understanding the
      interface coupling is thus of primary importance for fundamental science and
      applications. Here we study twisted multilayer graphene flakes with multi
      wavelength Raman spectroscopy. We find a significant intensity enhancement of the
      interlayer coupling modes (C peaks) due to resonance with new optically allowed
      electronic transitions, determined by the relative orientation of the layers. The
      interlayer coupling results in a Davydov splitting of the C peak in systems
      consisting of two equivalent graphene multilayers. This allows us to directly
      quantify the interlayer interaction, which is much smaller compared with Bernal
      stacked interfaces. This paves the way to the use of Raman spectroscopy to
      uncover the interface coupling of two-dimensional hybrids and heterostructures. 

PMID- 25382100
TI  - Microtubule orientation and spacing within bundles is critical for long-range
      kinesin-1 motility.
AB  - Cells rely on active transport to quickly organize cellular cargo. How cells
      regulate transport is not fully understood. One proposed mechanism is that motor
      activity could be altered through the architecture of the cytoskeleton. This
      mechanism is supported by the fact that the cytoskeletal network is tightly
      regulated in cells and filament polarity within networks dictates motor
      directionality. For instance, axons contain bundles of parallel microtubules and
      all cargos with the same motor species will move in the same direction. It is not
      clear how other types of networks, such as antiparallel bundles in dendrites, can
      regulate motor transport. To understand how the organization of microtubules
      within bundles can regulate transport, we studied kinesin-1 motility on three
      bundle types: random-polarity bundles that are close-packed, parallel polarity
      bundles, and antiparallel polarity bundles that are spaced apart. We find that
      close-packed bundles inhibit motor motion, while parallel arrays support
      unidirectional motion. Spacing the microtubules with microtubule-associated
      proteins enhances run lengths. Our results indicate that microtubule bundle
      architecture dictates the motion of single motors and could have effects on cargo
      transport. (c) 2014 Wiley Periodicals, Inc. 

PMID- 25382101
TI  - Intratumoral injection of Ad-ISF35 (Chimeric CD154) breaks tolerance and induces
      lymphoma tumor regression.
AB  - Ad-ISF35, an adenovirus vector encoding a membrane-bound engineered CD154
      chimeric protein (ISF35), induces complete A20 lymphoma tumor regression in mice
      after intratumoral direct injection (IDI). Ad-ISF35 induced durable local and
      systemic antitumor responses associated with a rapid tumor infiltration of
      macrophages and neutrophils as well as increased levels of proinflammatory
      cytokines in the tumor microenvironment. Ad-ISF35 IDI transduced preferentially
      fibroblasts and macrophages present in the tumor microenvironment, and ISF35
      protein expression was observed in only 0.25% of cells present in the tumor.
      Moreover, Ad-ISF35 IDI induced upregulation of CD40 in tumor and immune
      regulatory cells, including those that did not express ISF35, suggesting the
      presence of a strong bystander effect. These responses resulted in the generation
      of IFN-gamma-secreting cytotoxic lymphocytes and the production of specific
      cytotoxic antibodies against lymphoma cells. Overall, cellular immune therapy
      based on ISF35 induced phenotypic changes in the tumor cells and tumor
      microenvironment that were associated with a break in tumor immune tolerance and
      a curative antitumor effect in this lymphoma mouse model. Our data highlight the
      potential activity that modulation of costimulatory signaling has in cancer
      therapy. 

PMID- 25382102
TI  - Comparison of incidence of hyponatremia between intranasal and oral desmopressin
      in patients with central diabetes insipidus.
AB  - Central diabetes insipidus (CDI), which is characterized by polyuria and
      polydipsia, is caused by a deficiency of the antidiuretic hormone arginine
      vasopressin (AVP). While CDI is treated with desmopressin, an analogue of AVP,
      the intranasal formulation is inconvenient and CDI patients reportedly prefer the
      oral formulation to the intranasal one. In Japan, intranasal desmopressin had
      been the only formulation for the treatment of CDI until 2012, when the
      desmopressin orally disintegrating tablet (ODT) was approved for treatment. In
      this study we analyzed 26 patients with CDI in whom intranasal desmopressin was
      switched to desmopressin ODT. The mean daily dose of intranasal desmopressin was
      10 +/- 8 MUg/day, and that of desmopressin ODT was 142 +/- 59 MUg/day. The mean
      serum sodium levels were 140 +/- 5 mmol/L and 140 +/- 3 mmol/L with intranasal
      desmopressin and desmopressin ODT, respectively, and there were no significant
      differences between these values. The frequency of hyponatremia (<135 mmol/L)
      with intranasal desmopressin was 11.7% and that with desmopressin ODT was 7.6%,
      while the frequency of hyponatremia (<130 mmol/L) with intranasal desmopressin
      was 4.2% and that with desmopressin ODT was 1.3%. Statistical analyses revealed
      that incidence of hyponatremia was significantly decreased after the switch to
      desmopressin ODT. Thus, it is suggested that water balance is better controlled
      with desmopressin ODT than with intranasal desmopressin in patients with CDI. 

PMID- 25382103
TI  - Baroreflex activation therapy: a new treatment option for heart failure with
      reduced ejection fraction.
AB  - Sympathovagal imbalance plays a major role in the progression of heart failure
      with reduced ejection fraction. Baroreflex activation therapy (BAT) by electrical
      stimulation of baroreceptors located at the carotid sinus can reduce sympathetic
      and increase parasympathetic tone. This review provides an overview on the
      concept of BAT in heart failure with reduced ejection fraction and available
      preclinical and clinical data. Animal studies of BAT in heart failure with
      reduced ejection fraction have demonstrated a decline in plasma norepinephrine,
      an improved left ventricular ejection fraction, a reduced susceptibility to
      induced ventricular arrhythmias and a survival benefit. First clinical data from
      uncontrolled studies suggest a relevant improvement in muscle sympathetic nerve
      activity, ejection fraction, 6-min walk distance, New York Heart Association
      (NYHA) class and hospitalization rate. BAT appears to be safe in this severely
      ill patient population.

PMID- 25382104
TI  - Identification of novel tyrosine kinase inhibitors for drug resistant T315I
      mutant BCR-ABL: a virtual screening and molecular dynamics simulations study.
AB  - BCR-ABL tyrosine kinase plays a major role in the pathogenesis of chronic myeloid
      leukemia (CML) and is a proven target for drug development. Currently available
      drugs in the market are effective against CML; however, side-effects and drug
      resistant mutations in BCR-ABL limit their full potential. Using high throughput
      virtual screening approach, we have screened several small molecule databases and
      docked against wild-type and drug resistant T315I mutant BCR-ABL. Drugs that are
      currently available, such as imatinib and ponatinib, were also docked against BCR
      ABL protein to set a cutoff value for our screening. Selected lead compounds were
      further evaluated for chemical reactivity employing density functional theory
      approach, all selected ligands shows HLG value > 0.09900 and the binding free
      energy between protein-ligand complex interactions obtained was rescored using MM
      GBSA. The selected compounds showed least DeltaG score -71.53 KJ/mol to maximum 
      126.71 KJ/mol in both wild type and drug resistant T315I mutant BCR-ABL.
      Following which, the stability of the docking complexes were evaluated by
      molecular dynamics simulation (MD) using GROMACS4.5.5. Results uncovered seven
      lead molecules, designated with Drug-Bank and PubChem ids as DB07107, DB06977,
      ST013616, DB04200, ST007180 ST019342, and DB01172, which shows docking scores
      higher than imatinib and ponatinib.

PMID- 25382106
TI  - Influence of a cis,syn-cyclobutane pyrimidine dimer damage on DNA conformation
      studied by molecular dynamics simulations.
AB  - The photo-induced formation of cis-syn-cyclobutane pyrimidine dimers (CPD) is a
      highly mutagenic and cancerogenic DNA lesion. In bacteria photolyases can
      efficiently reverse the dimer formation employing a light-driven reaction after
      looping out the CPD damaged bases into the enzyme active site. The exact
      mechanism how the repair enzyme identifies a damaged site within a large surplus
      of undamaged DNA is not fully understood. The CPD damage may alter the DNA
      structure and dynamics already in the absence of the repair enzyme which can
      facilitate the initial binding of a photolyase repair enzyme. To characterize the
      effect of a CPD damage, extensive comparative molecular dynamics (MD) simulations
      on duplex DNA with central regular or CPD damaged nucleotides were performed
      supplemented with simulations of the DNA-photolyase complex. Although no
      spontaneous flipping out transitions of the damaged bases were observed, the
      simulations showed significant differences in the conformational states of
      regular and CPD damage DNA. The isolated damaged DNA adopted transient
      conformations which resembled the global shape of the repair enzyme bound
      conformation more closely compared to regular B-DNA. In particular, these
      conformational changes were observed in most of helical and structural parameters
      where the protein bound DNA differs drastically from regular B-DNA. It is likely
      that the transient overlap of isolated DNA with the enzyme bound DNA conformation
      plays a decisive role for the specific and rapid initial recognition by the
      repair enzyme prior to the looping out process of the damaged DNA.

PMID- 25382105
TI  - Obstructive sleep apnea and the risk of perinatal outcomes: a meta-analysis of
      cohort studies.
AB  - Inconsistent information exists in the relationship between obstructive sleep
      apnea (OSA) and perinatal outcomes. This study was intended to investigate
      whether OSA in pregnant women has a potential to elevate the incidence of the
      maternal and neonatal outcomes by performing a meta-analysis of all available
      cohort studies. Five cohort studies including 977 participants were eligible for
      inclusion. The association between OSA and the risk of perinatal outcomes was
      expressed as relative risks (RR), with 95% confidence interval (CI). Our results
      revealed that OSA group was associated with more frequent preeclampsia (RR 1.96;
      95% CI 1.34 to 2.86), preterm birth (RR 1.90; 95%CI 1.24 to 2.91), cesarean
      delivery (RR 1.87; 95% CI 1.52 to 2.29) and neonatal intensive care unit (NICU)
      (RR 2.65; 95% CI 1.86 to 3.76). On analyzing data for the prevalence of
      gestational diabetes and small gestational age (SGA) < 10th percentile (RR 1.40;
      95% CI 0.62 to 3.19, and RR 0.64; 95%CI 0.33 to1.24, respectively), there were no
      significant differences in both group. Findings from this meta-analysis indicate
      that OSA in pregnant women significantly increases the incidence of maternal and
      neonatal outcomes, which is associated with more frequent preeclampsia, preterm
      birth, cesarean delivery and NICU admission. 

PMID- 25382107
TI  - A simplified emergency trauma score for predicting mortality in emergency
      setting.
AB  - AIMS: The aim of the study was to develop a simplified emergency trauma score
      (SETS) for rating injury severity as well as triaging and predicting mortality in
      Hong Kong. BACKGROUND: Many existing trauma scoring systems require measurements
      that are not generally available in emergency settings in Hong Kong. As many of
      these important measures in the scoring systems are not available before the
      patients are admitted in the hospitals, it may delay treatment because of the
      extent of a patient's injury is often not clear at the site of accident or in the
      emergency settings. DESIGN: A retrospective cohort analysis of trauma patients'
      records from Trauma Registry in Hong Kong was performed. METHOD: Potential
      significant parameters in predicting mortality were identified by univariate
      analysis. Binary logistic regression then was used to develop an equation for
      SETS. Four parameters including age, Glasgow coma scale, respiratory rate and
      American College of Surgeons (ACS) mechanism of injury were identified, and the
      reliability and validity of SETS was assessed. RESULTS: At cut-off point of a
      SETS score of 60, the sensitivity and specificity of SETS were 64% and 98%
      respectively. The area under receiver operating characteristic curve was 0.939
      which was comparable with other commonly used trauma scores. CONCLUSIONS: SETS
      should be considered a relevant trauma scoring system in Hong Kong emergency
      settings. It is suggested that similar scoring systems should be developed in
      other countries based upon obtainable measures in their corresponding emergency
      settings. RELEVANCE TO CLINICAL PRACTICE: As a trauma scoring system is closely
      related to the context of its application, a system that can facilitate accurate
      sorting of patients into treatment hierarchies should be adopted in the congested
      emergency settings.

PMID- 25382108
TI  - Factors predicting survival in peripheral T-cell lymphoma in the USA: a
      population-based analysis of 8802 patients in the modern era.
AB  - Current prognostic models for peripheral T-cell lymphoma (PTCL) have multiple
      limitations, and questions exist regarding applicability to current patients. We
      utilized the Surveillance Epidemiology and End Results (SEER)-18 database to
      evaluate factors affecting overall survival (OS) of PTCL in the modern era and
      identified 8802 patients between 2000-2010. Most subtypes of PTCL increased in
      incidence during the study period. In univariate analyses, age >55 years, black
      race, advanced stage, absence of extra-nodal disease, omission of radiation
      therapy (RT) and high-risk histology each predicted inferior OS (P < 0.0001).
      Multivariate analysis (MVA) demonstrated that hepatosplenic, enteropathy
      associated and extra-nodal Natural Killer/T cell histologies, each had hazard
      ratios >1.5 (P <= 0.0001) for death. Further, age >=55 years, black race and
      advanced stage maintained their significance in the MVA (P < 0.0001 each). Based
      on the significant factors, a prognostic model was constructed and subsequently
      validated in an independent cohort. The new model incorporated age, stage,
      histology and race, with an OS ranging from 9 months (highest risk group) to 120
      months (lowest risk group). In summary, this is the largest study of PTCL
      patients in the modern era that provides risk stratification utilizing a new
      prognostic model that can be incorporated into future prospective clinical
      trials.

PMID- 25382109
TI  - Exploiting the narrow gap of rearrangement between the substituents in the
      vicinal disubstitution reactions of diaryliodonium salts with pyridine N
      sulfonamidates.
AB  - The vicinal disubstitution reactions of diaryliodonium salts with pyridine N
      sulfonamidates to give o-pyridinium anilines were fully examined. A reaction
      pathway of N-arylation occurring at the amidate group followed by a radical
      rearrangement is proposed. The electronic effects of various substituents in this
      radical rearrangement were investigated. 

PMID- 25382110
TI  - Adoptive transfer of bone marrow-derived dendritic cells decreases inhibitory and
      regulatory T-cell differentiation and improves survival in murine polymicrobial
      sepsis.
AB  - A decrease in the number of dendritic cells (DCs) is a major cause of post-sepsis
      immunosuppression and opportunistic infection and is closely associated with poor
      prognosis. Increasing the number of DCs to replenish their numbers post sepsis
      can improve the condition. This therapeutic approach could improve recovery after
      sepsis. Eighty C57BL/6 mice were subjected to sham or caecal ligation and
      puncture (CLP) surgery. Mice were divided into four groups: (i) Sham + vehicle,
      (ii) Sham + DC, (iii) CLP + vehicle, and (iv) CLP + DC. Bone-marrow-derived DCs
      (BMDCs) were administered at 6, 12 and 24 hr after surgery. After 3 days, we
      assessed serum indices of organ function (alanine aminotransferase, aspartate
      aminotransferase, creatinine, amylase and lipase), organ tissue histopathology
      (haematoxylin and eosin staining), cytokine [interferon-gamma (IFN-gamma), tumour
      necrosis factor-alpha, interleukin-12p70 (IL-12p70), IL-6 and IL-10] levels in
      the serum, programmed death-1 (PD-1) expression on T cells, regulatory T-cell
      differentiation in the spleen, and the survival rate (monitored for 7 days). BMDC
      transfer resulted in the following changes: a significant reduction in damage to
      the liver, kidney and pancreas in the CLP-septic mice as well as in the
      pathological changes seen in the liver, lung, small intestine and pancreas;
      significantly elevated levels of the T helper type 1 (Th1) cytokines IFN-gamma
      and IL-12p70 in the serum; decreased levels of the Th2 cytokines IL-6 and IL-10
      in the serum; reduced expression of PD-1 molecules on CD4(+) T cells; reduced the
      proliferation and differentiation of splenic suppressor T cells and CD4(+) 
      CD25(+)  Foxp3(+) regulatory T cells, and a significant increase in the survival
      rate of the septic animals. These results show that administration of BMDCs may
      have modulated the differentiation and immune function of T cells and contributed
      to alleviate immunosuppression, hence reducing organ damage and mortality post
      sepsis. Hence, the immunoregulatory effect of BMDC treatment has potential for
      the treatment of sepsis. 

PMID- 25382111
TI  - Hyperplasia of the submucosal glands of the columnar-lined oesophagus.
AB  - AIM: To evaluate the presence of multi-layered epithelium (ME) and to compare the
      distribution, size and morphology of the oesophageal submucosal glands (SMG)
      beneath reflux exposed metaplastic columnar mucosa with those of normal squamous
      epithelium in patients with columnar-lined oesophagus (CLO). METHODS AND RESULTS:
      In eight oesophageal resection specimens, the SMG of the metaplastic segments
      were significantly larger than those in the squamous segments of patients with
      CLO (0.81 versus 0.56 mm(2) , P = <0.001). There was an accumulation of SMG close
      to the neosquamocolumnar junction (NSCJ), as indicated by a higher median
      frequency of SMG (0.080 SMG/mm) compared with that of the squamous (0.013 SMG/mm)
      and metaplastic segments (0.031 SMG/mm) (P = 0.022). The frequency of ME was
      significantly higher in the metaplastic compared with the normal squamous
      segments (1/158 mm and 1/341 mm, respectively, P = 0.028) and ME was found almost
      exclusively (96%) in direct connection with the excretory ducts of SMG.
      CONCLUSIONS: Hyperplasia of SMG in the metaplastic segment, accumulation of SMG
      near the NSCJ, the presence of ME in connection with the excretory ducts of SMG
      and metaplasia are all reflux-induced morphological changes, possibly induced by
      stimulation of progenitors in the excretory ducts of the SMG.

PMID- 25382112
TI  - Novel GNAL mutations in two German patients with sporadic dystonia.

PMID- 25382113
TI  - Low prevalence and incidence of Helicobacter pylori infection in children: a
      population-based study in Japan.
AB  - BACKGROUND: Infection of Helicobacter pylori mainly occurs in childhood. In
      Japan, incidence of gastric cancer is still high in the senior citizen
      population, but little is known about the current H. pylori infection status
      among children or their family members. METHODS: As a population-based study, the
      prevalence of H. pylori infection and change in infection status over a 1-year
      interval in children were determined. Family members of some participants were
      also invited to participate in the study to determine their infection status. All
      children of specific ages attending 16 schools in Sasayama, Hyogo Prefecture,
      were invited to participate. H. pylori infection was determined by the stool
      antigen test and diagnosis confirmed by polymerase chain reaction and the urea
      breath test. RESULTS: Helicobacter pylori prevalence was 1.9% among 689 children
      aged 0-8 years in 2010 and 1.8% among 835 children aged 0-11 in 2011. No feco
      conversion was observed in 430 children aged 0-8 years (170 were aged 0-4 years)
      who provided follow-up stool samples after 1 year. The prevalence of infection
      was 6% (2 of 33) and 38% (6 of 16) in mothers of negative and positive probands
      (p = .04), respectively, and 12% (3 of 25) and 50% (8 of 16) (p = .01),
      respectively, in fathers. CONCLUSION: Helicobacter pylori prevalence in Japanese
      children is approximately 1.8%, which is much lower than that reported in
      Japanese adults. New infection may be rare. Parent-to-child infection is thought
      to be the main infection route of the infrequent infection for children in Japan.

PMID- 25382114
TI  - A case of nasal chromoblastomycosis causing epistaxis.
AB  - BACKGROUND: Chromoblastomycosis is a chronic fungal infection of the skin and
      subcutaneous tissue that most commonly affects the feet and lower limbs. It is
      rare for this infection to occur on the face, and it is exceptionally rare for it
      to involve the nose and sinuses. This paper reports a rare case of nasal
      chromoblastomycosis in a 50-year-old Malaysian male. CASE REPORT: The patient,
      who was a rubber plantation worker in the southern state of Johor, presented to
      the ENT clinic with a history of epistaxis. He did not recall any history of
      injury to the nose. Nasal endoscopy showed a pale yellowish lesion at the
      inferior edge of the left middle turbinate. Histology revealed that this was a
      case of chromoblastomycosis. CONCLUSION: Chromoblastomycosis of the nasal cavity
      is very rare and can be mistaken for other granulomatous conditions in the nose.
      It progresses very slowly over many years. Our patient was managed
      conservatively, as he was not keen on undergoing surgical intervention. Lesion
      size remained the same at five months' follow up, with no recurrence of
      epistaxis.

PMID- 25382115
TI  - Conjugation of a new series of dithiocarbazate Schiff base Copper(II) complexes
      with vectors selected to enhance antibacterial activity.
AB  - A new series of six Schiff bases derived from S-methyldithiocarbazate (SMDTC) and
      S-benzyldithiocarbazate (SBDTC) with methyl levulinate (SMML, SBML), levulinic
      acid (SMLA, SBLA), and 4-carboxybenzaldehyde (SM4CB, SB4CB) were reacted with
      copper(II), producing complexes of general formula ML2 (M = Cu(II), L = ligand).
      All compounds were characterized using established physicochemical and
      spectroscopic methods. Crystal structures were determined for three Schiff bases
      (SMML, SBML, SBLA) and two Cu(II) complexes (Cu(SMML)2 and Cu(SMLA)2). In order
      to provide more insight into the behavior of the complexes in solution, electron
      paramagnetic resonance (EPR) and electrochemical experiments were performed. The
      parent ligands and their respective copper(II) complexes exhibited moderate
      antibacterial activity against both Gram-negative and Gram-positive bacteria. The
      most active ligand (SB4CB) and its analogous S-methyl derivative (SM4CB) were
      conjugated with various vector moieties: polyarginines (R1, R4, R9, and RW9),
      oligoethylene glycol (OEG), and an efflux pump blocker, phenylalanine-arginine
      beta-naphthylamide (PAbetaN). Nonaarginine (R9) derivatives showed the most
      encouraging synergistic effects upon conjugation and complexation with copper ion
      including enhanced water solubility, bacteria cell membrane permeability, and
      bioactivity. These Cu(II)-R9 derivatives display remarkable antibacterial
      activity against a wide spectrum of bacteria and, in particular, are highly
      efficacious against Staphylococcus aureus with minimum inhibitory concentration
      (MIC) values of 0.5-1 MUM. This pioneer study clearly indicates that the
      conjugation of cell-penetrating peptides (CPPs) to dithiocarbazate compounds
      greatly enhances their therapeutic potential. 

PMID- 25382116
TI  - Photolytic N2 splitting: a road to sustainable NH3 production?
AB  - The split up: Recent advances in photochemical dinitrogen splitting have been
      achieved. Demonstration of the reversibility of the N2 splitting and ammonia
      formation from a nitride has advanced the field of N2 fixation using a synthetic
      homogeneous system. 

PMID- 25382117
TI  - Immune checkpoint inhibitors for non-small-cell lung cancer: does that represent
      a 'new frontier'?
AB  - Advances in the interpretation and understanding of cancer behaviour,
      particularly of its ability to evade the host immunosurveillance, deregulating
      the balance between inhibitory and stimulatory factors, led to the development of
      an innovative category of immunotherapeutic agents, currently under
      investigation. Although the disappointing data deriving from the employment of
      vaccines in non-small cell lung cancer (NSCLC), more promising results have been
      obtained in the early phase trials with immune checkpoint inhibitors, such as
      cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death
      protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. This review
      delineates the main features of the available immunotherapeutic agents, focusing
      the discussion on immune checkpoint inhibitors, those that have already
      demonstrated a relevant clinical activity (such as Ipilimumab and Nivolumab) and
      those molecules still in early development phase. Moreover, we underline the
      possible emerging issues deriving from the progressive diffusion of Immuno
      Oncology into the standard clinical practice. The careful and accurate
      identification and management of immune-related toxicities, the validation of
      more reliable immune response criteria and the increasing research of potential
      predictive biomarkers are key points of discussion. The perspective is that
      immunotherapy might represent an effective 'magic bullet', able to change the
      treatment paradigm of NSCLC, particularly of those subgroups featured by a
      heavily mutant cancer (squamous histology and smokers), where the immunologic
      agents contribute in cancer development and progression seems to be strong and,
      concurrently, the efficacy of standard therapies particularly limited.

PMID- 25382120
TI  - Life Origination Hydrate Hypothesis (LOH-Hypothesis).
AB  - The paper develops the Life Origination Hydrate Hypothesis (LOH-hypothesis),
      according to which living-matter simplest elements (LMSEs, which are N-bases,
      riboses, nucleosides, nucleotides), DNA- and RNA-like molecules, amino-acids, and
      proto-cells repeatedly originated on the basis of thermodynamically controlled,
      natural, and inevitable processes governed by universal physical and chemical
      laws from CH4, niters, and phosphates under the Earth's surface or seabed within
      the crystal cavities of the honeycomb methane-hydrate structure at low
      temperatures; the chemical processes passed slowly through all successive
      chemical steps in the direction that is determined by a gradual decrease in the
      Gibbs free energy of reacting systems. The hypothesis formulation method is based
      on the thermodynamic directedness of natural movement and consists ofan attempt
      to mentally backtrack on the progression of nature and thus reveal principal
      milestones alongits route. The changes in Gibbs free energy are estimated for
      different steps of the living-matter origination process; special attention is
      paid to the processes of proto-cell formation. Just the occurrence of the gas
      hydrate periodic honeycomb matrix filled with LMSEs almost completely in its
      final state accounts for size limitation in the DNA functional groups and the
      nonrandom location of N-bases in the DNA chains. The slowness of the low
      temperature chemical transformations and their "thermodynamic front" guide the
      gross process of living matter origination and its successive steps. It is shown
      that the hypothesis is thermodynamically justified and testable and that many
      observed natural phenomena count in its favor. 

PMID- 25382119
TI  - Is life unique?
AB  - Is life physicochemically unique? No. Is life unique? Yes. Life manifests
      innumerable formalisms that cannot be generated or explained by physicodynamics
      alone. Life pursues thousands of biofunctional goals, not the least of which is
      staying alive. Neither physicodynamics, nor evolution, pursue goals. Life is
      largely directed by linear digital programming and by the Prescriptive
      Information (PI) instantiated particularly into physicodynamically indeterminate
      nucleotide sequencing. Epigenomic controls only compound the sophistication of
      these formalisms. Life employs representationalism through the use of symbol
      systems. Life manifests autonomy, homeostasis far from equilibrium in the
      harshest of environments, positive and negative feedback mechanisms, prevention
      and correction of its own errors, and organization of its components into
      Sustained Functional Systems (SFS). Chance and necessity-heat agitation and the
      cause-and-effect determinism of nature's orderliness-cannot spawn formalisms such
      as mathematics, language, symbol systems, coding, decoding, logic, organization
      (not to be confused with mere self-ordering), integration of circuits,
      computational success, and the pursuit of functionality. All of these
      characteristics of life are formal, not physical. 

PMID- 25382121
TI  - The capricious character of nature.
AB  - The on-going whole genome sequencing and whole cell assays of metabolites and
      proteins imply that complex systems could ultimately be mastered by perfecting
      knowledge into great detail. However, courses of nature are inherently
      intractable because flows of energy and their driving forces depend on each
      other. Thus no data will suffice to predict precisely the outcomes of e.g.,
      engineering experiments. All path-dependent processes, most notably evolution in
      its entirety, display this capricious character of nature. 

PMID- 25382123
TI  - Optimization of a nonviral transfection system to evaluate Cox-2 controlled
      interleukin-4 expression for osteoarthritis gene therapy in vitro.
AB  - BACKGROUND: Gene therapy appears to have the potential for achieving a long-term
      remedy for osteoarthritis (OA). However, there is a risk of adverse reactions,
      especially when using cytomegalovirus-controlled expression. To provide a safe
      application, we focused on the expression of therapeutic cytokines [e.g.
      interleukin (IL)-4] in a disease-responsive manner by use of the previously
      cloned Cox-2 promoter as 'genetic switch'. In the present study, we report the
      functionality of a controlled gene therapeutic system in an equine osteoarthritic
      cell model. METHODS: Different nonviral transfection reagents were tested for
      their efficiency on equine chondrocytes stimulated with equine IL-1beta or
      lipopolysaccharide to create an inflammatory environment. To optimize the
      transfection, we successfully redesigned the vector by excluding the internal
      ribosomal entry site (IRES). The functionality of our Cox-2 promoter construct
      with respect to expressing IL-4 was proven at the mRNA and protein levels and the
      anti-inflammatory potential of IL-4 was confirmed by analyzing the expression of
      IL-1beta, IL-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3 and tumor necrosis
      factor (TNF)-alpha using a quantitative polymerase chain reaction. RESULTS:
      Nonviral transfection reagents yielded transfection rates from 21% to 44% with
      control vectors with and without IRES, respectively. Stimulation of equine
      chondrocytes resulted in a 20-fold increase of mRNA expression of IL-1beta. Such
      exogenous stimulation of chondrocytes transfected with pNCox2-IL4 led to an
      increase of IL-4 mRNA expression, whereas expression of inflammatory mediators
      decreased. The timely link between these events confirms the anti-inflammatory
      potential of synthesized IL-4. CONCLUSIONS: We consider that this approach has
      significant potential for translation into a useful anti-inflammation therapy.
      Molecular tools such as the described therapeutic plasmid pave the way for a
      local-controlled, self-limiting gene therapy.

PMID- 25382124
TI  - Is there a role of C-reactive protein in red blood cell aggregation?
AB  - INTRODUCTION: Numerous clinical studies related the plasma level of C-reactive
      protein (CRP) to the erythrocyte sedimentation rate (ESR) independent of the kind
      of disease. The molecular regulation of the process is unknown. METHODS: We
      performed a meta-analysis of 10 previous studies and experimentally probed for a
      direct action of CRP on red blood cells (RBCs) by different methods including
      determination of a microscopic aggregation index, Ca(2+) imaging and analysis of
      sedimentation experiments. RESULTS: The meta-analysis revealed a statistically
      significant correlation (Pearson coefficient of 0.37; P < 0.0001), but we could
      not find any experimental evidence for a direct CRP-RBC interaction. Instead, we
      could confirm a correlation between fibrinogen level and ESR. CONCLUSION:
      Therefore, we concluded that CRP and ESR cannot account for nor replace each
      other as a diagnostic measure. The correlation between CRP level and ESR is most
      probably caused by fibrinogen, because its increase coincides with elevated CRP
      levels.

PMID- 25382125
TI  - Abietane diterpenoids from Salvia sclarea transformed roots as growth inhibitors
      of pathogenic Acanthamoeba spp.
AB  - Amoebae from the genus Acanthamoeba are known agents leading to various diseases
      such as granulomatous amoebic encephalitis (GAE), a chronic progressive disease
      of the central nervous system, amoebic keratitis (AK), chronic eye infection,
      amoebic pneumitis (AP), chronic lung infection, and skin infections. It is known
      that various synthetic anti-Acanthamoeba substances are ineffective. Therefore,
      other substances, e.g., natural plant compounds, are the focus of biological
      investigations regarding anti-parasite activity. In this work, the ability of
      four abietane diterpenoids (ferruginol, salvipisone, aethiopinone, and 1-oxo
      aethiopinone) to inhibit Acanthamoeba growth is reported. All investigated
      compounds were active against Acanthamoeba growing in vitro. Among them,
      ferruginol demonstrated the highest activity against Acanthamoeba. This compound
      inhibited Acanthamoeba growth by about 72% in a 3-day exposure period (IC50 17.45
      MUM), while aethiopinone and 1-oxo-aethiopinone demonstrated this activity at the
      level of 55-56%. Salvipisone reduced the growth of Acanthamoeba in vitro culture
      by 39%. For this compound, the value of IC50 was 701.94 MUM after 72 h of
      exposure.

PMID- 25382126
TI  - The 2014 International Stop Pressure Ulcer Day: EPUAP needs you.

PMID- 25382127
TI  - Using a silicone-based dressing as a primary wound contact layer.
AB  - The use of silicone-based dressings as a primary contact layer for wound care can
      prevent epithelial stripping, pain and sensitivity and have been widely available
      for nearly 20 years. Cuticell Contact from BSN medical is the latest silicone
      based dressing to add to the armoury of the wound care clinician. Using
      documented case studies the author explores the reasoning behind why clinicians
      should consider re-examining the use of silicone dressings. 

PMID- 25382122
TI  - Primal eukaryogenesis: on the communal nature of precellular States, ancestral to
      modern life.
AB  - This problem-oriented, exploratory and hypothesis-driven discourse toward the
      unknown combines several basic tenets: (i) a photo-active metal sulfide scenario
      of primal biogenesis in the porespace of shallow sedimentary flats, in contrast
      to hot deep-sea hydrothermal vent conditions; (ii) an inherently complex communal
      system at the common root of present life forms; (iii) a high degree of internal
      compartmentalization at this communal root, progressively resembling coenocytic
      (syncytial) super-cells; (iv) a direct connection from such communal super-cells
      to proto-eukaryotic macro-cell organization; and (v) multiple rounds of micro
      cellular escape with streamlined reductive evolution-leading to the major
      prokaryotic cell lines, as well as to megaviruses and other viral lineages.
      Hopefully, such nontraditional concepts and approaches will contribute to
      coherent and plausible views about the origins and early life on Earth. In
      particular, the coevolutionary emergence from a communal system at the common
      root can most naturally explain the vast discrepancy in subcellular organization
      between modern eukaryotes on the one hand and both archaea and bacteria on the
      other. 

PMID- 25382128
TI  - Using no-rinse skin wipes to treat incontinence-associated dermatitis.
AB  - Individuals who suffer with incontinence, especially in relation to faeces, will
      often be at risk of skin breakdown and develop incontinence-associated dermatitis
      (IAD) which, if left untreated, can lead to pressure ulcer formation ( Gray, 2004
      ). IAD is caused by increased, unrelieved moisture against the skin, usually from
      liquid faeces and urine, which can then weaken the skin integrity. The integrity
      of the skin in this area is also at risk of pressure ulcers caused by shear or
      friction ( Beeckman et al, 2010a ). Treatment and prevention of IAD lesions
      involves a three-step process used in post-incontinence episodes, which includes
      cleansing, moisturisation and protection of the skin ( Beeckman et al, 2011a ).
      Using a wipe covers all of these steps immediately following incontinence
      episodes ( Ronner et al, 2010 ). This reduces the need to gather a number of
      different items required for post-incontinence skin care, which usually includes
      a dry wipe to be soaked in soapy water to wash the skin, a moisturiser to replace
      lost moisture and a skin protectant to prevent moisture from direct contact with
      the skin ( Foxley and Baadjies, 2009 ). This article will give some examples of
      the use of a particular continence and cleansing wipe in clinical practice. 

PMID- 25382129
TI  - Transparency must prevail.

PMID- 25382130
TI  - Evaluating a pressure-redistribution mattress replacement system.
AB  - Pressure ulcer prevention is high on the quality agenda and provision of pressure
      relieving equipment to meet patients' needs is an essential part of this process.
      This can be challenging in today's NHS and this article explores the evaluation
      process that supported the procurement of the AtmosAirTM 4000 pressure
      redistributing mattress replacement system. Outcomes suggest that, when combined
      with a robust repositioning and skin assessment regime, the AtmosAir 4000
      performed well and dynamic mattress usage was reduced. Further evaluation over a
      longer period of time will be undertaken in future. 

PMID- 25382131
TI  - Polymeric membrane dressing for radiotherapy-induced skin reactions.
AB  - Post-radiotherapy treatment depends on how the skin within the treatment field
      has reacted during radiotherapy for cancer. Skin reactions can range from mild
      dull erythema and tightening of the skin to severe moist desquamation, which may
      result in wounds that can be painful and sloughy. It is estimated that
      approximately 87% of patients will experience a moderate-to-severe skin reaction.
      This article discusses an evaluation of the use of a polymeric membrane dressing
      (PolyMem(r), Aspen Medical) in 23 patients with skin reactions following
      radiotherapy. A purpose-designed evaluation form was completed over a period of 4
      weeks or until healed. Patients were asked to complete both qualitative
      descriptions and numerical scores of pain for symptoms and procedural pain. Skin
      healing, pain and sleep patterns were all evaluated, with additional qualitative
      input on the patient experience. Successful symptom management regarding pain,
      exudate control and patient comfort was documented in both clinical observations
      and patient diaries. 

PMID- 25382132
TI  - Elevation devices for the prevention of heel pressure ulcers: a review.
AB  - AIM: The objective of this systematic literature review was to gain insight into
      the effectiveness of off-loading devices to prevent heel pressure ulcers within
      the acute hospital setting. BACKGROUND: Heels have been identified as the second
      most common site for pressure ulcers. Devices which off-load pressure can include
      pillows, wedges and boots. It is unclear as to which method or device is best at
      preventing pressure ulcers. DESIGN AND METHODS: A systematic review was carried
      out through the search of electronic databases and bibliographies of relevant
      publications. Randomised controlled trials (RCTs) and systematic reviews that
      compared devices which off-load heels to prevent pressure ulcers were identified.
      RESULTS: A total of five studies were included in the review. The methodological
      quality of the studies was generally poor. The studies reported that heel-boot
      elevation devices appeared more beneficial. However, poor compliance with wearing
      the devices was identified, as well as a perceived increased risk of falls. There
      were little data on cost-effectiveness. CONCLUSIONS: There is little high-quality
      trial evidence to support the routine use of heel devices to prevent pressure
      ulcers. However, they may have a role to play within a multifaceted programme of
      pressure-ulcer prevention.

PMID- 25382133
TI  - A topical haemoglobin spray for oxygenating chronic venous leg ulcers: a pilot
      study.
AB  - Acute wounds will generally heal independently of any interventions, whereas
      chronic wounds are chronic for a reason and are unlikely to successfully heal
      without intervention. In the treatment of venous leg ulcers, the gold standard
      will always be compression therapy. However, many wounds still do not heal
      despite best practice. Therefore, the use of adjunct therapies alongside standard
      care become the priority for healing. This article describes a small evaluation,
      involving 17 patients with chronic venous leg ulcers, that set out to determine
      the effect of a topical oxygen therapy on wound size. The therapy comprises a
      canister that sprays pure haemoglobin in a water solution into the wound. The
      haemoglobin spray needs to be used at least once every 3 days, and no training is
      required on its use. Results showed the device helped promote wound healing in 14
      out of 17 wounds treated for more than 2 weeks. These patients had previously
      been shown to be non-healing during a 4-week run-in period where they received
      standard care, including compression therapy. 

PMID- 25382118
TI  - Theory of the origin, evolution, and nature of life.
AB  - Life is an inordinately complex unsolved puzzle. Despite significant theoretical
      progress, experimental anomalies, paradoxes, and enigmas have revealed
      paradigmatic limitations. Thus, the advancement of scientific understanding
      requires new models that resolve fundamental problems. Here, I present a
      theoretical framework that economically fits evidence accumulated from
      examinations of life. This theory is based upon a straightforward and non
      mathematical core model and proposes unique yet empirically consistent
      explanations for major phenomena including, but not limited to, quantum gravity,
      phase transitions of water, why living systems are predominantly CHNOPS (carbon,
      hydrogen, nitrogen, oxygen, phosphorus, and sulfur), homochirality of sugars and
      amino acids, homeoviscous adaptation, triplet code, and DNA mutations. The
      theoretical framework unifies the macrocosmic and microcosmic realms, validates
      predicted laws of nature, and solves the puzzle of the origin and evolution of
      cellular life in the universe. 

PMID- 25382134
TI  - CAPN10 SNP43 G>A gene polymorphism and type 2 diabetes mellitus in the Asian
      population: a meta-analysis of 9353 participants.
AB  - A correlation between the single nucleotide polymorphism (SNP)43 G>A in the
      calpain-10 (CAPN10) gene (i.e., CAPN10 SNP43) and type 2 diabetes mellitus (T2DM)
      susceptibility has been suggested, but the evidence for such a relationship
      remains controversial. To explore the association of the CAPN10 SNP43 with T2DM
      in Asian populations, a meta-analysis including 9,353 participants from 20
      individual studies in Asian populations was conducted. The pooled odds ratios
      (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated
      by a fixed-effect model or random-effect model. The relationship between CAPN10
      SNP43 and T2DM was significant under allelic (OR: 1.18, 95% CI: 1.01-1.38, P =
      0.03), recessive (OR: 1.236, 95% CI: 1.038-1.472, P =0.017), heterozygous (OR:
      1.261, 95% CI: 1.053-1.512, P = 0.012), and additive (OR: 1.183, 95% CI: 1.014
      1.381, P = 0.033) genetic models but not under dominant (OR: 1.12, 95% CI: 0.78
      1.62, P = 0.53) or homozygous (OR: 0.937, 95% CI: 0.648-1.355, P = 0.730) genetic
      models. CAPN10 SNP43 was significantly associated with T2DM susceptibility in
      Asian populations, especially in Chinese populations. Asians, particularly
      Chinese people with the SNP43 G allele of the CAPN10 gene may have an increased
      risk of developing T2DM. 

PMID- 25382137
TI  - The clinical challenge of preventing sudden cardiac death immediately after acute
      ST-elevation myocardial infarction.
AB  - Unfortunately, of all patients experiencing acute myocardial infarction (MI),
      usually in the form of ST-elevation MI, 25-35% will die of sudden cardiac death
      (SCD) before receiving medical attention, most often from ventricular
      fibrillation. For patients who reach the hospital, prognosis is considerably
      better and has improved over the years. Reperfusion therapy, best attained with
      primary percutaneous coronary intervention compared to thrombolysis, has made a
      big difference in reducing the risk of SCD early and late after ST-elevation MI.
      In-hospital SCD due to ventricular tachyarrhythmias is manageable, with either
      preventive measures or drugs or electrical cardioversion. There is general
      agreement for secondary prevention of SCD post-MI with implantation of a
      cardioverter defibrillator (ICD) when malignant ventricular arrhythmias occur
      late (>48 h) after an MI, and are not due to reversible or correctable causes.
      The major challenge remains that of primary prevention, that is, how to prevent
      SCD during the first 1-3 months after ST-elevation MI for patients who have low
      left ventricular ejection fraction and are not candidates for an ICD according to
      current guidelines, due to the results of two studies, which did not show any
      benefits of early (<40 days after an MI) ICD implantation. Two recent documents
      may provide direction as to how to bridge the gap for this early post-MI period.
      Both recommend an electrophysiology study to guide implantation of an ICD, at
      least for those developing syncope or non-sustained ventricular tachycardia, who
      have an inducible sustained ventricular tachycardia at the electrophysiology
      study. An ICD is also recommended for patients with indication for a permanent
      pacemaker due to bradyarrhythmias, who also meet primary prevention criteria for
      SCD. 

PMID- 25382136
TI  - Exposure to serotonin adversely affects oligodendrocyte development and
      myelination in vitro.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) has been implicated to play critical roles
      in early neural development. Recent reports have suggested that perinatal
      exposure to selective serotonin reuptake inhibitors (SSRIs) resulted in cortical
      network miswiring, abnormal social behavior, callosal myelin malformation, as
      well as oligodendrocyte (OL) pathology in rats. To gain further insight into the
      cellular and molecular mechanisms underlying SSRIs-induced OL and myelin
      abnormalities, we investigated the effect of 5-HT exposure on OL development,
      cell death, and myelination in cell culture models. First, we showed that 5-HT
      receptor 1A and 2A subtypes were expressed in OL lineages, using
      immunocytochemistry, Western blot, as well as intracellular Ca(2+) measurement.
      We then assessed the effect of serotonin exposure on the lineage development,
      expression of myelin proteins, cell death, and myelination, in purified OL and
      neuron-OL myelination cultures. For pure OL cultures, our results showed that 5
      HT exposure led to disturbance of OL development, as indicated by aberrant
      process outgrowth and reduced myelin proteins expression. At higher doses, such
      exposure triggered a development-dependent cell death, as immature OLs exhibited
      increasing susceptibility to 5-HT treatment compared to OL progenitor cells
      (OPC). We showed further that 5-HT-induced immature OL death was mediated at
      least partially via 5-HT2A receptor, since cell death could be mimicked by 5-HT2A
      receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride, (+/
      )-2,5-dimethoxy-4-iodoamphetamine hydrochloride, but atten-uated by pre-treatment
      with 5-HT2A receptor antagonist ritanserin. Utilizing a neuron-OL myelination co
      culture model, our data showed that 5-HT exposure significantly reduced the
      number of myelinated internodes. In contrast to cell injury observed in pure OL
      cultures, 5-HT exposure did not lead to OL death or reduced OL density in neuron
      OL co-cultures. However, abnormal patterns of contactin-associated protein
      (Caspr) clustering were observed at the sites of Node of Ranvier, suggesting that
      5-HT exposure may affect other axon-derived factors for myelination. In summary,
      this is the first study to demonstrate that manipulation of serotonin levels
      affects OL development and myelination, which may contribute to altered neural
      connectivity noted in SSRIs-treated animals. The current in vitro study
      demonstrated that exposure to high level of serotonin (5-HT) led to aberrant
      oligodendrocyte (OL) development, cell injury, and myelination deficit. We
      propose that elevated extracellular serotonin levels in the fetal brain, such as
      upon the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy,
      may adversely affect OL development and/or myelination, thus contributing to
      altered neural connectivity seen in Autism Spectrum Disorders. OPC =
      oligodendrocyte progenitor cell. 

PMID- 25382138
TI  - Community dynamics of prokaryotic and eukaryotic microbes in an estuary
      reservoir.
AB  - This study demonstrates both prokaryotic and eukaryotic community structures and
      dominant taxonomies in different positions of the greatest estuary reservoir for
      drinking water source in the world in four seasons of one year using 454
      pyrosequencing method with total of 312,949 16S rRNA and 374,752 18S rRNA gene
      fragments, including 1,652 bacteria OTUs and 1,182 fungus OTUs. During winter and
      spring, the community composition at the phylum level showed that microorganisms
      had similar structures but their quantities were different. Similarly, obvious
      changes at the genus level were observed among the samples taken in winter and
      spring between summer and fall. Microorganisms located the reservoir inlet were
      founded to be different from those in rear at both phylum and genus level. Air
      temperature had a stronger effect than sampling location on the microbial
      community structure. Total nitrogen and dissolved oxygen were algae-monitoring
      indicators during the whole year. Moreover, Bacillus was an efficient indicator
      during summer and autumn for bacteria OTUs. 

PMID- 25382140
TI  - On-surface synthesis of organometallic complex via metal-alkene interactions.
AB  - From the interplay of high-resolution scanning tunneling microscopy (STM)
      imaging/manipulation and density functional theory (DFT) calculations, we have
      shown that the spontaneous formation of an organometallic complex by copper
      alkene interactions can be successfully achieved, where the specific molecular
      adsorption geometry is revealed to be the key for facilitating such interaction. 

PMID- 25382139
TI  - Platinum-free counter electrode comprised of metal-organic-framework (MOF)
      derived cobalt sulfide nanoparticles for efficient dye-sensitized solar cells
      (DSSCs).
AB  - We fabricated a highly efficient (with a solar-to-electricity conversion
      efficiency (eta) of 8.1%) Pt-free dye-sensitized solar cell (DSSC). The counter
      electrode was made of cobalt sulfide (CoS) nanoparticles synthesized via
      surfactant-assisted preparation of a metal organic framework, ZIF-67, with
      controllable particle sizes (50 to 320 nm) and subsequent oxidation and sulfide
      conversion. In contrast to conventional Pt counter electrodes, the synthesized
      CoS nanoparticles exhibited higher external surface areas and roughness factors,
      as evidenced by X-ray diffraction (XRD), scanning electron microscopy (SEM)
      element mapping, and electrochemical analysis. Incident photon-to-current
      conversion efficiency (IPCE) results showed an increase in the open circuit
      voltage (VOC) and a decrease in the short-circuit photocurrent density (Jsc) for
      CoS-based DSSCs compared to Pt-based DSSCs, resulting in a similar power
      conversion efficiency. The CoS-based DSSC fabricated in the study show great
      potential for economically friendly production of Pt-free DSSCs.

PMID- 25382141
TI  - Journalists and public health professionals: challenges of a symbiotic
      relationship.
AB  - Journalists and health professionals share a symbiotic relationship during a
      disease outbreak as both professions play an important role in informing the
      public's perceptions and the decisions of policy makers. Although critics in the
      United States have focused on US reporters and media outlets whose coverage has
      been sensationalist and alarmist, the discussion in this article is based on the
      ideal--gold standard--for US journalists. Journalists perform three primary
      functions during times of health crises: disseminating accurate information to
      the public, medical professionals, and policy makers; acting as the go-between
      for the public and decision makers and health and science experts; and monitoring
      the performance of institutions responsible for the public health response. A
      journalist's goal is to responsibly inform the public in order to optimize the
      public health goals of prevention while minimizing panic. The struggle to strike
      a balance between humanizing a story and protecting the dignity of patients while
      also capturing the severity of an epidemic is harder in the era of the 24-7 news
      cycle. Journalists grapple with dueling pressures: confirming that their
      information is correct while meeting the demand for rapid updates. Just as health
      care professionals triage patients, journalists triage information. The challenge
      going forward will be how to get ahead of the story from the onset, racing
      against the pace of digital dissemination of misinformation by continuing to
      refine the media-science relationship.

PMID- 25382142
TI  - Mice with megalencephalic leukoencephalopathy with cysts: a developmental angle.
AB  - OBJECTIVE: Megalencephalic leukoencephalopathy with cysts (MLC) is a genetic
      disease characterized by infantile onset white matter edema and delayed onset
      neurological deterioration. Loss of MLC1 function causes MLC. MLC1 is involved in
      ion-water homeostasis, but its exact role is unknown. We generated Mlc1-null mice
      for further studies. METHODS: We investigated which brain cell types express
      MLC1, compared developmental expression in mice and men, and studied the
      consequences of loss of MLC1 in Mlc1-null mice. RESULTS: Like humans, mice
      expressed MLC1 only in astrocytes, especially those facing fluid-brain barriers.
      In mice, MLC1 expression increased until 3 weeks and then stabilized. In humans,
      MLC1 expression was highest in the first year, decreased, and stabilized from
      approximately 5 years. Mlc1-null mice had early onset megalencephaly and
      increased brain water content. From 3 weeks, abnormal astrocytes were present
      with swollen processes abutting fluid-brain barriers. From 3 months, widespread
      white matter vacuolization with intramyelinic edema developed. Mlc1-null
      astrocytes showed slowed regulatory volume decrease and reduced volume-regulated
      anion currents, which increased upon MLC1 re-expression. Mlc1-null astrocytes
      showed reduced expression of adhesion molecule GlialCAM and chloride channel ClC
      2, but no substantial changes in other known MLC1-interacting proteins.
      INTERPRETATION: Mlc1-null mice replicate early stages of the human disease with
      early onset intramyelinic edema. The cellular functional defects, described for
      human MLC, were confirmed. The earliest change was astrocytic swelling,
      substantiating that in MLC the primary defect is in volume regulation by
      astrocytes. MLC1 expression affects expression of GlialCAM and ClC-2. Abnormal
      interplay between these proteins is part of the pathomechanisms of MLC.

PMID- 25382143
TI  - Genome-wide association study of Arabidopsis thaliana leaf microbial community.
AB  - Identifying the factors that influence the outcome of host-microbial interactions
      is critical to protecting biodiversity, minimizing agricultural losses and
      improving human health. A few genes that determine symbiosis or resistance to
      infectious disease have been identified in model species, but a comprehensive
      examination of how a host genotype influences the structure of its microbial
      community is lacking. Here we report the results of a field experiment with the
      model plant Arabidopsis thaliana to identify the fungi and bacteria that colonize
      its leaves and the host loci that influence the microbe numbers. The composition
      of this community differs among accessions of A. thaliana. Genome-wide
      association studies (GWAS) suggest that plant loci responsible for defense and
      cell wall integrity affect variation in this community. Furthermore, species
      richness in the bacterial community is shaped by host genetic variation, notably
      at loci that also influence the reproduction of viruses, trichome branching and
      morphogenesis. 

PMID- 25382144
TI  - Modeling metabolic syndrome and its association with cognition: the Northern
      Manhattan study.
AB  - Metabolic syndrome (MetS) is a clustering of vascular risk factors and is
      associated with increased risk of cardiovascular disease. Less is known about the
      relationship between MetS and cognition. We examined component vascular risk
      factors of MetS as correlates of different cognitive domains. The Northern
      Manhattan Study (NOMAS) includes 1290 stroke-free participants from a largely
      Hispanic multi-ethnic urban community. We used structural equation modeling (SEM)
      to model latent variables of MetS, assessed at baseline and an average of 10
      years later, at which time participants also underwent a full cognitive battery.
      The two four-factor models, of the metabolic syndrome (blood pressure, lipid
      levels, obesity, and fasting glucose) and of cognition (language, executive
      function, psychomotor, and memory), were each well supported (CFI=0.97 and
      CFI=0.95, respectively). When the two models were combined, the correlation
      between metabolic syndrome and cognition was -.31. Among the metabolic syndrome
      components, only blood pressure uniquely predicted all four cognitive domains.
      After adjusting for age, gender, race/ethnicity, education, smoking, alcohol, and
      risk factor treatment variables, blood pressure remained a significant correlate
      of all domains except memory. In this stroke-free race/ethnically diverse
      community-based cohort, MetS was associated with cognitive function suggesting
      that MetS and its components may be important predictors of cognitive outcomes.
      After adjusting for sociodemographic and vascular risk factors, blood pressure
      was the strongest correlate of cognitive performance. Findings suggest MetS, and
      in particular blood pressure, may represent markers of vascular or
      neurodegenerative damage in aging populations.

PMID- 25382146
TI  - A doubly robust estimator for the attributable benefit of a treatment regime.
AB  - The identification and study of treatment regimes (algorithms or policies for
      dictating treatments to patients) are a growing area of study in the statistical
      sciences. Many methods have been put forth to identify the 'best' or optimal
      treatment regime from observed data. Once the optimal treatment regime is
      identified, a secondary question of interest is to determine the public health
      impact of that health policy. Simply put, what is the benefit that can be
      attributed to using such a regime in practice? The attributable benefit of a
      treatment regime is a measure of the reduction in poor outcomes that would have
      been observed had the regime of interest been utilized. Methods for identifying
      the optimal treatment regime can use statistical modeling techniques which are
      susceptible to model misspecification in the identification of both the optimal
      treatment regime and its attributable benefit. Using notions from causal
      inference and building upon previous work, this paper identifies an estimator for
      attributable benefit that offers a second layer of protection in cases where an
      outcome regression model may be misspecified. The estimator is dubbed doubly
      robust in that it is unbiased for the true benefit if either a model for the
      outcome or a propensity model for treatment is correctly specified. Large sample
      properties are explored, and two sets of confidence intervals proposed.
      Simulation studies compare the proposed estimator with previous work, with a
      focus on model misspecification. The estimator is applied to real data to examine
      its utility in practice.

PMID- 25382145
TI  - Aerosol-mediated delivery of AAV2/6-IkappaBalpha attenuates lipopolysaccharide
      induced acute lung injury in rats.
AB  - Inhibition of the proinflammatory transcription factor NF-kappaB has previously
      been shown to attenuate the inflammatory response in tissue after injury.
      However, the feasibility and efficacy of aerosolized adeno-associated viral (AAV)
      vector-delivered transgenes to inhibit the NF-kappaB pathway are less clear.
      Initial studies optimized the AAV vector for delivery of transgenes to the
      pulmonary epithelium. The effect of repeated nebulization on the integrity and
      transduction efficacy of the AAV vector was then examined. Subsequent in vivo
      studies examined the efficacy of aerosolized rAAV2/6 overexpressing the NF-kappaB
      inhibitor IkappaBalpha in a rodent endotoxin-induced lung injury model. Initial
      in vitro investigations indicated that rAAV2/6 was the most effective vector to
      transduce the lung epithelium, and maintained its integrity and transduction
      efficacy after repeated nebulization. In our in vivo studies, animals that
      received aerosolized rAAV2/6-IkappaBalpha demonstrated a significant increase in
      total IkappaBalpha levels in lung tissue relative to null vector-treated animals.
      Aerosolized rAAV2/6-IkappaBalpha attenuated endotoxin-induced bronchoalveolar
      lavage-detected neutrophilia, interleukin-6 and cytokine-induced neutrophil
      chemoattractant-1 levels, as well as total protein content, and decreased
      histologic indices of injury. These results demonstrate that aerosolized AAV
      vectors encoding human IkappaBalpha significantly attenuate endotoxin-mediated
      lung injury and may be a potential therapeutic candidate in the treatment of
      acute lung injury. 

PMID- 25382149
TI  - Does trauma in the primary dentition cause sequelae in permanent successors? A
      systematic review.
AB  - This systematic review sought scientific evidence (in the literature) that trauma
      in the primary incisors cause sequelae in permanent successors. Also this work
      verified whether there was a relation between the presence and type of sequelae
      in permanent teeth with the child's age at the time of injury and type of trauma.
      Electronic databases, including the PubMed, Scopus, The Cochrane Library, LILACS,
      and Web of Science were used to search for original articles up to June 2013.
      Prospective and retrospective studies that assessed the association of trauma in
      deciduous incisors and developmental disturbances in permanent successors were
      selected. Two authors independently reviewed and extracted the data from the
      included studies. A methodological quality assessment evaluation of the selected
      studies was performed. The search retrieved 258 citations. Initially, 19 studies
      fulfilled the selection criteria; however, one (1) was excluded, leaving 18 for
      the final selection. Despite some limitations in the study designs were observed,
      especially the lack of a control group in most studies, the evidence found
      suggests that individuals with trauma in their primary incisors have more
      developmental disorders in the permanent successors than individuals without a
      previous trauma. Furthermore, the younger the child is at the time of injury, the
      more frequent and more severe are the sequelae to the permanent successor
      incisors. More severe traumas such as intrusion and avulsion are associated to
      more serious developmental disorders. These results should be analyzed carefully
      because very few studies evaluated had a control group. 

PMID- 25382151
TI  - Current status of antibody therapy in ALL.
AB  - Despite the significant advances in modern chemotherapy, it remains challenging
      to treat adult patients with acute lymphoblastic leukaemia (ALL). The relapse
      rate remains high, and the outcome at the time of relapse is dismal. Antibody
      based therapies have demonstrated promising results in this patient group.
      Variable mechanisms have been applied to target surface antigens (CD20 [also
      termed MS4A1], CD22, CD52 and CD19) that are commonly expressed on malignant
      leukaemia cells. In this review, we will focus on the clinical application of
      such therapies in adult ALL, including the naked antibodies: Rituximab,
      Ofatumumab, Epratuzumab and Alemtuzumab; the immunotoxins: BL22 and Combotox; the
      immunoconjugates: inotuzumab and SAR 3419; as well as the Bi-specific T cell
      engaging (BiTE)-specific antibody, Blinatumomab. 

PMID- 25382152
TI  - Proton-induced generation of remote N-heterocyclic carbene-Ru complexes.
AB  - The proton-induced Ru-C bond variation, which was previously found to be relevant
      in the water oxidation, has been investigated by using cyclometalated ruthenium
      complexes with three phenanthroline (phen) isomers. The designed complexes,
      [Ru(bpy)2 (1,5-phen)](+) ([2](+)), [Ru(bpy)2 (1,6-phen)](+) ([3](+)), and
      [Ru(bpy)2 (1,7-phen)](+) ([4](+)) were newly synthesized and their structural and
      electronic properties were analyzed by various spectroscopy and theoretical
      protocols. Protonation of [4](+) triggered profound electronic structural change
      to form remote N-heterocyclic carbene (rNHC), whereas protonation of [2](+) and
      [3](+) did not affect their structures. It was found that changes in the
      electronic structure of phen beyond classical resonance forms control the rNHC
      behavior. The present study provides new insights into the ligand design of
      related ruthenium catalysts.

PMID- 25382153
TI  - Controlled preparation of porous TiO2-Ag nanostructures through supramolecular
      assembly for plasmon-enhanced photocatalysis.
AB  - By templating Ag(+)-induced supramolecular assembly at different temperatures,
      porous TiO2-Ag nanotubes and nanospheres are fabricated in a controlled manner
      due to the effect of Rayleigh instability. Compared with traditional TiO2
      nanoparticles, TiO2-Ag nanostructures above show much more extensive visible
      light absorption and exhibit the noticeably plasmon-enhanced photocatalysis
      because of the existence of Ag nanoparticles.

PMID- 25382150
TI  - Glucose metabolism in pigs expressing human genes under an insulin promoter.
AB  - BACKGROUND: Xenotransplantation of porcine islets can reverse diabetes in non
      human primates. The remaining hurdles for clinical application include safe and
      effective T-cell-directed immunosuppression, but protection against the innate
      immune system and coagulation dysfunction may be more difficult to achieve. Islet
      targeted genetic manipulation of islet-source pigs represents a powerful tool to
      protect against graft loss. However, whether these genetic alterations would
      impair islet function is unknown. METHODS: On a background of alpha1,3
      galactosyltransferase gene-knockout (GTKO)/human (h)CD46, additional genes
      (hCD39, human tissue factor pathway inhibitor, porcine CTLA4-Ig) were inserted in
      different combinations under an insulin promoter to promote expression in islets
      (confirmed by immunofluorescence). Seven pigs were tested for baseline and
      glucose/arginine-challenged levels of glucose, insulin, C-peptide, and glucagon.
      RESULTS: This preliminary study did not show definite evidence of beta-cell
      deficiencies, even when three transgenes were expressed under the insulin
      promoter. Of seven animals, all were normoglycemic at fasting, and five of seven
      had normal glucose disposal rates after challenge. All animals exhibited insulin,
      C-peptide, and glucagon responses to both glucose and arginine challenge;
      however, significant interindividual variation was observed. CONCLUSIONS:
      Multiple islet-targeted transgenic expression was not associated with an overtly
      detrimental effect on islet function, suggesting that complex genetic constructs
      designed for islet protection warrants further testing in islet
      xenotransplantation models.

PMID- 25382154
TI  - Validity of footprint analysis to determine flatfoot using clinical diagnosis as
      the gold standard in a random sample aged 40 years and older.
AB  - BACKGROUND: Research is needed to determine the prevalence and variables
      associated with the diagnosis of flatfoot, and to evaluate the validity of three
      footprint analysis methods for diagnosing flatfoot, using clinical diagnosis as a
      benchmark. METHODS: We conducted a cross-sectional study of a population-based
      random sample >= 40 years old (n = 1002) in A Coruna, Spain. Anthropometric
      variables, Charlson's comorbidity score, and podiatric examination (including
      measurement of Clarke's angle, the Chippaux-Smirak index, and the Staheli index)
      were used for comparison with a clinical diagnosis method using a podoscope.
      Multivariate regression was performed. Informed patient consent and ethical
      review approval were obtained. RESULTS: Prevalence of flatfoot in the left and
      right footprint, measured using the podoscope, was 19.0% and 18.9%, respectively.
      Variables independently associated with flatfoot diagnosis were age (OR 1.07),
      female gender (OR 3.55) and BMI (OR 1.39). The area under the receiver operating
      characteristic curve (AUC) showed that Clarke's angle is highly accurate in
      predicting flatfoot (AUC 0.94), followed by the Chippaux-Smirak (AUC 0.83) and
      Staheli (AUC 0.80) indices. Sensitivity values were 89.8% for Clarke's angle,
      94.2% for the Chippaux-Smirak index, and 81.8% for the Staheli index, with
      respective positive likelihood ratios or 9.7, 2.1, and 2.0. CONCLUSIONS: Age,
      gender, and BMI were associated with a flatfoot diagnosis. The indices studied
      are suitable for diagnosing flatfoot in adults, especially Clarke's angle, which
      is highly accurate for flatfoot diagnosis in this population.

PMID- 25382155
TI  - PFO closure with only fluoroscopic guidance: 7 years real-world single centre
      experience.
AB  - AIMS: To evaluate the safety and the efficacy of fluoroscopy-guided only (Fluo-G)
      and of echocardiography-guided (Echo-G; trans-esophageal echocardiography-TEE-or
      intracardiac echocardiography-ICE) percutaneous closure of patent foramen ovale
      (PFO). METHODS AND RESULTS: Single center retrospective registry enrolling 368
      consecutive patients (mean age 50.5 years) who underwent PFO closure between June
      2004 and December 2011. Most patients had prior cryptogenic stroke (n = 126;
      34.2%), TIA (n = 218; 51.1%); some of these had recurrent neurological events
      [multiple strokes n = 28 (7.8%); multiple TIAs n = 72 (18.6%)]. All the patients
      underwent a preprocedure TEE. PFO closure was performed with Echo-G in 187
      patients (50.8%) (TEE n = 69, 36.8% and ICE n = 124, 66.3%). In Fluo-G cases, PFO
      with atrial septal aneurysm (ASA) was significantly less present (P < 0.005) and
      smaller devices (<25 mm) were implanted more frequently (P < 0.001). Both
      fluoroscopy and total procedural time were lower in the Fluo-G group (P <
      0.0001). No differences were found in terms of successful device deployment
      (98.3% Fluo-G vs. 98.3% Echo-G) and RtL-shunt at follow-up (11.7% Fluo-G vs. 7.6%
      Echo-G). The rate of conversion from Fluoro-G to Echo-G procedure was 4.4% (n =
      8). At a median follow-up of 4 years, freedom from recurrent embolic events rate
      was similar between the two groups (Echo-G 94.5 vs. Fluo-G 95.7%). CONCLUSIONS:
      In our experience Fluoro-G PFO closure was performed mainly in cases of simple
      anatomy, with similar results in terms of safety and efficacy compared to Echo-G
      cases. Both fluoroscopy and total procedural times were lower in the Fluo-G
      cases.

PMID- 25382156
TI  - Stereoselective uptake of cell-penetrating peptides is conserved in antisense
      oligonucleotide polyplexes.
AB  - Stereochemistry matters. A significant conceptual advancement is presented toward
      the understanding of how functional characteristics of delivery peptides can
      translate into functional characteristics of peptide-based oligoplexes. 

PMID- 25382157
TI  - Maternal use of selective serotonin reuptake inhibitors and risk of miscarriage -
      assessing potential biases.
AB  - BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) during
      pregnancy has been associated with miscarriage, but the association may be biased
      by maternal mental illness, lifestyle and exposure misclassification. METHODS: A
      register study on all pregnancies in Denmark between 1996 and 2009 was conducted
      using individualised data from the Danish National Patient Register, the Medical
      Birth Register, the Danish Psychiatric Central Register, the Danish National
      Prescription database and the Danish National Birth Cohort (DNBC). RESULTS: A
      total of 1 191164 pregnancies were included in the study, of which 98275 also
      participated in the DNBC. Pregnancies exposed to SSRIs during or before pregnancy
      were more likely than unexposed pregnancies to result in first trimester
      miscarriage, hazard rate (HR)=1.08 [95% confidence interval (CI) 1.04, 1.13] and
      HR=1.26 [95% CI 1.16, 1.37], respectively. No difference was observed for second
      trimester miscarriage. SSRI-exposed pregnancies without a maternal
      depression/anxiety diagnosis from a psychiatric department were less likely to
      result in first trimester miscarriage than unexposed pregnancies with a
      diagnosis, HR=0.85 [95% CI 0.76, 0.95]. SSRI-exposed pregnancies were
      characterised by an unhealthier maternal lifestyle and mental health profile than
      unexposed pregnancies, whereas no convincing differences were observed between
      pregnancies exposed to SSRIs during versus before pregnancy. Substantial
      disagreement was found between prescriptions and self-reported use of SSRIs, but
      it did not affect the estimated hazard ratios. CONCLUSION: Confounding by
      indication and lifestyle in pregnancy may explain the association between SSRI
      use and miscarriage.

PMID- 25382158
TI  - A smoothed finite element method for analysis of anisotropic large deformation of
      passive rabbit ventricles in diastole.
AB  - The smoothed FEM (S-FEM) is firstly extended to explore the behavior of 3D
      anisotropic large deformation of rabbit ventricles during the passive filling
      process in diastole. Because of the incompressibility of myocardium, a special
      method called selective face-based/node-based S-FEM using four-node tetrahedral
      elements (FS/NS-FEM-TET4) is adopted in order to avoid volumetric locking. To
      validate the proposed algorithms of FS/NS-FEM-TET4, the 3D Lame problem is
      implemented. The performance contest results show that our FS/NS-FEM-TET4 is
      accurate, volumetric locking-free and insensitive to mesh distortion than
      standard linear FEM because of absence of isoparametric mapping. Actually, the
      efficiency of FS/NS-FEM-TET4 is comparable with higher-order FEM, such as 10-node
      tetrahedral elements. The proposed method for Holzapfel myocardium hyperelastic
      strain energy is also validated by simple shear tests through the comparison
      outcomes reported in available references. Finally, the FS/NS-FEM-TET4 is applied
      in the example of the passive filling of MRI-based rabbit ventricles with fiber
      architecture derived from rule-based algorithm to demonstrate its efficiency.
      Hence, we conclude that FS/NS-FEM-TET4 is a promising alternative other than FEM
      in passive cardiac mechanics.

PMID- 25382159
TI  - Thematic analysis of psychiatric patients' perceptions of nursing staff.
AB  - Therapeutic and informal interactions with nurses are integral to the quality of
      care that psychiatric patients receive. How well these interactions are
      performed, and their impact on the experience and outcomes of inpatient care,
      have not been subject to systematic evaluation. The aim of the present study was
      to examine patients' perceptions of the personal and professional qualities of
      nursing staff and how these contribute to the ward environment. Patients (n =
      119) from 16 acute psychiatric wards were interviewed using a schedule developed
      by a service-user researcher. Transcriptions of interviews were coded and
      organized into six themes: staff duties, staff disposition, control,
      communication and engagement, therapeutic ward environment, and consistency.
      Patients recognized that nurses have a difficult and stressful job, but
      frequently expressed feelings of anger, frustration, and hopelessness about their
      experience of the wards. Patients frequently felt that nursing staff did not
      understand issues from their perspective or attempt to empathize with them. The
      findings indicate poorly-communicated and inconsistent care. Initiatives to
      improve patients' experiences of acute psychiatric wards are urgently needed. 

PMID- 25382162
TI  - The impact of caregivers on the effectiveness of an early community mental health
      detection and intervention programme in Hong Kong.
AB  - AIM: The prevalence rate of mental illness in Chinese communities is high, but
      Chinese clients tend to underutilize mental health services. Caregivers may play
      an important role in mental health early detection and intervention, but few
      studies have investigated their roles in community mental health services. This
      study compared the effectiveness of an early detection and intervention
      programme, the Community Mental Health Intervention Project, for two groups in
      the context of Hong Kong - clients with and without caregivers. METHOD: A
      comparison group pre-post-test design was adopted. A total of 170 service users
      joined this study, including 100 with caregivers and 70 without caregivers.
      RESULTS: Both groups showed a significant decrease in psychiatric symptoms and
      increase in community living skills; the group without caregivers indicated a
      greater reduction in psychiatric symptoms. Different social work intervention
      components had different predictive effects on these changes. CONCLUSION: The
      Community Mental Health Intervention Project is an effective early detection and
      intervention programme in working with Hong Kong Chinese people who are suspected
      of having mental health problems, especially for those without caregivers.

PMID- 25382161
TI  - EuroInf: a multicenter comparative observational study of apomorphine and
      levodopa infusion in Parkinson's disease.
AB  - Subcutaneous apomorphine infusion (Apo) and intrajejunal levodopa infusion (IJLI)
      are two treatment options for patients with advanced Parkinson's disease (PD) and
      refractory motor complications, with varying cost of treatment. There are no
      multicenter studies comparing the effects of the two strategies. This open-label,
      prospective, observational, 6-month, multicenter study compared 43 patients on
      Apo (48.8% males, age 62.3 +/- 10.6 years; disease duration: 14 +/- 4.4 years;
      median H & Y stage 3; interquartile range [IQR]: 3-4) and 44 on IJLI (56.8%
      males, age 62.7 +/- 9.1 years; disease duration: 16.1 +/- 6.7 years; median H & Y
      stage 4; IQR, 3-4). Cohen's effect sizes (>=0.8 considered as large) were "large"
      with both therapies with respect to total motor, nonmotor, and quality-of-life
      scores. The Non-Motor Symptoms Scale (NMSS) with Apo showed moderate improvement,
      whereas sleep/fatigue, gastrointestinal, urinary, and sexual dimensions of the
      NMSS showed significantly higher improvement with IJLI. Seventy-five percent on
      IJLI improved in their quality-of-life and nonmotor symptoms (NMS), whereas in
      the Apo group, a similar proportion improved in quality of life, but 40% in NMS.
      Adverse effects included peritonitis with IJLI and skin nodules on Apo. Based on
      this open-label, nonrandomized, comparative study, we report that, in advanced
      Parkinson's patients, both IJLI and Apo infusion therapy appear to provide a
      robust improvement in motor symptoms, motor complications, quality-of-life, and
      some NMS. Controlled, randomized studies are required.

PMID- 25382163
TI  - Histopathological evaluation of caffeine-loaded solid lipid nanoparticles in
      efficient treatment of cellulite.
AB  - CONTEXT: Cellulite refers to dimpled appearance of the skin, usually located in
      the thighs and buttocks regions of most adult women. OBJECTIVE: The aim of this
      study was to formulate topically used caffeine-loaded solid lipid nanoparticle
      (SLN) for the treatment of cellulite. METHODS: SLNs were prepared by hot
      homogenization technique using Precirol(r) as lipid phase. The physical
      characterization and stability studies of SLNs as well as in vitro skin
      permeation and histological studies in rat skin were conducted. RESULTS: The mean
      particle size, encapsulation efficiency and loading efficiency percentages for
      optimized SLN formulation were 94 nm, 86 and 28%, respectively. In vitro drug
      release demonstrated that caffeine-loaded SLN incorporated into carbopol made
      hydrogel (caffeine-SLN-hydrogel) exhibited a sustained drug release compared to
      the caffeine hydrogel over 24 h. Caffeine-loaded SLNs showed a good stability
      during 12 months of storage at room temperature. The DSC and XRD results showed
      that caffeine was dispersed in SLN in an amorphous state. In vitro permeation
      studies illustrated higher drug accumulation in the skin with caffeine-SLN
      hydrogel compared to caffeine hydrogel. The flux value of caffeine through rat
      skin in caffeine-SLN-hydrogel was 3.3 times less than caffeine hydrogel,
      representing lower systemic absorption. In contrast with caffeine hydrogel, the
      histological studies showed the complete lysis of adipocytes by administration of
      caffeine-SLN-hydrogel in the deeper skin layers. CONCLUSION: Results of this
      study indicated that SLNs are promising carrier for improvement of caffeine
      efficiency in the treatment of cellulite following topical application on the
      skin.

PMID- 25382164
TI  - Effective spatially fractionated GRID radiation treatment planning for a passive
      grid block.
AB  - OBJECTIVE: To commission a grid block for spatially fractionated grid radiation
      therapy (SFGRT) treatments and describe its clinical implementation and
      verification through the record and verify (R&V) system. METHODS: SFGRT was
      developed as a treatment modality for bulky tumours that cannot be easily
      controlled with conventionally fractionated radiation. Treatment is delivered in
      the form of open-closed areas. Currently, SFGRT is performed by either using a
      commercially available grid block or a multileaf collimator (MLC) of a linear
      accelerator. In this work, 6-MV photon beam was used to study dosimetric
      characteristics of the grid block. We inserted the grid block into a commercially
      available treatment planning system (TPS), and the feasibility of delivering such
      treatment plans on a linear accelerator using a R&V system was verified. Dose
      measurements were performed using a miniature PinPoint(TM) ion chamber (PTW,
      Freiburg, Germany) in a water phantom and radiochromic film within solid water
      slabs. PinPoint ion chamber was used to measure the output factors, percentage
      depth dose (PDD) curves and beam profiles at two depths, depth of maximum dose
      (zmax) and 10 cm. Film sheets were used to measure dose profiles at zmax and 10
      cm depth. RESULTS: The largest observed percentage difference between output
      factors for the grid block technique calculated by the TPS and measured with the
      PinPoint ion chamber was 3.6% for the 5 * 5-cm(2) field size. Relatively
      significant discrepancies between measured and calculated PDD values appear only
      in the build-up region, which was found to amount to <4%, while a good agreement
      (differences <2%) at depths beyond zmax was observed. Dose verification
      comparisons performed between calculated and measured dose distributions were in
      clinically acceptable agreements. When comparing the MLC-based with the grid
      block technique, the advantage of treating large tumours with a single field
      reduces treatment time by at least 3-5 times, having significant impact on
      patient throughput. CONCLUSION: The proposed method supports and helps to
      standardize the clinical implementation of the grid block in a safer and more
      accurate way. ADVANCES IN KNOWLEDGE: This work describes the method to implement
      treatment planning for the grid block technique in radiotherapy departments.

PMID- 25382165
TI  - Emergence of Thelazia callipaeda Infection in Dogs and Cats from East-Central
      Portugal.
AB  - The eyeworm Thelazia callipaeda (Spirurida, Thelaziidae) infects domestic
      animals, wildlife and human beings, and is considered an emerging pathogen in
      Europe. This study aimed at investigating the prevalence and risk factors of T.
      callipaeda infection in dogs and cats from east-central Portugal, a region where
      the parasite was previously detected in two red foxes (Vulpes vulpes). Thelazia
      callipaeda was found in 22 (3.8%) of 586 dogs and in four (23.5%) of 17 cats. A
      total of 178 adult worms (71.9% of females and 28.1% of males) were collected
      from the conjunctiva of the infected dogs. The number of worms collected per dog
      ranged from 1 to 35 (average +/- standard deviation: 8.08 +/- 9.49), with four
      dogs (18.2%) harbouring only a single parasite. Worms were gathered from dogs
      throughout all months of the year. A total of 17 adult worms (64.7% of females
      and 35.3% of males) were obtained from cats. The number of worms per cat ranged
      from 1 to 14 (4.3 +/- 6.5), with three cats (75.0%) having a single parasite.
      Eyeworm infection was statistically more prevalent in pastoral and farm dogs, in
      those dogs with contact with other animals and in dogs with ocular
      manifestations. T. callipaeda is endemic in the east-central part of Portugal,
      reportedly infecting domestic (dogs and cats) and wild carnivores (red foxes) and
      evidencing a southerly dissemination. Future investigations should be focused on
      determining the local distribution and density of the insect vector (Phortica
      variegata) in this geographical area. This emergent zoonosis should be included
      by veterinarians, physicians and ophthalmologists in the differential diagnosis
      of ocular manifestations in their patients, particularly in areas where T.
      callipaeda is endemic. 

PMID- 25382166
TI  - Jordanian survivors' experiences of recovery from critical illness: a qualitative
      study.
AB  - BACKGROUND: Despite the fact that a lot of patients consider their discharge from
      hospitals as a positive sign of progress towards regained health, many of them
      start suffering from physical, psychological and social problems after discharge
      from intensive care units. AIM: This study aims to describe the experiences of
      Jordanian survivors of critical illnesses 3 months after discharge from a
      hospital intensive care unit. METHODS: A descriptive qualitative approach was
      used to involve 18 Jordanian patients from two hospitals in a major Jordanian
      city using open-ended interviews. Interview transcripts were analysed using
      content analysis method. RESULTS: Three main themes have emerged from the data:
      (1) new meaning of life; (2) different perspectives on the meaning of life, and
      (3) struggle for role identity. LIMITATION: The sample was chosen from one city
      in Jordan; longitudinal study might help identify the change in patients'
      experiences over time. CONCLUSION: Patients described the discharge from the
      intensive care unit as a means of rescue from death; they began to value their
      spiritual and religious rituals. Negative traumatic experiences hindered the
      patients' recovery process. During recovery, patients struggled to resume their
      power and role in family. IMPLICATIONS FOR NURSES AND HEALTH POLICY: This study
      emphasizes the importance of providing care according to the patient's individual
      needs, related to their cultural and spiritual milieu; there is a need to develop
      follow-up services for ICU survivors within a national health policy. Further
      educational and training programmes in the patient's issues after discharge from
      hospital are needed. This will definitely help nurses care after this patient
      group.

PMID- 25382167
TI  - Flexible enantioselectivity of tryptophanase attributable to benzene ring in
      heterocyclic moiety of d-tryptophan.
AB  - The invariance principle of enzyme enantioselectivity must be absolute because it
      is absolutely essential to the homochiral biological world. Most enzymes are
      strictly enantioselective, and tryptophanase is one of the enzymes with extreme
      absolute enantioselectivity for L-tryptophan. Contrary to conventional knowledge
      about the principle, tryptophanase becomes flexible to catalyze D-tryptophan in
      the presence of diammonium hydrogenphosphate. Since D-amino acids are ordinarily
      inert or function as inhibitors even though they are bound to the active site,
      the inhibition behavior of D-tryptophan and several inhibitors involved in this
      process was examined in terms of kinetics to explain the reason for this flexible
      enantioselectivity in the presence of diammonium hydrogenphosphate. Diammonium
      hydrogenphosphate gave tryptophanase a small conformational change so that D
      tryptophan could work as a substrate. As opposed to other D-amino acids, D
      tryptophan is a very bulky amino acid with a benzene ring in its heterocyclic
      moiety, and so we suggest that this structural feature makes the catalysis of D
      tryptophan degradation possible, consequently leading to the flexible
      enantioselectivity. The present results not only help to understand the mechanism
      of enzyme enantioselectivity, but also shed light on the origin of homochirality.

PMID- 25382168
TI  - Minimally invasive necrosectomy using resectoscope for intractable necrotic
      abscess after severe acute pancreatitis: report of a case.
AB  - CASE REPORT: A 43-year-old male was admitted to a regional hospital after being
      diagnosed with severe acute pancreatitis. The patient developed a pancreatic
      abscess with multiple organ failure. He was transferred to our hospital in
      critical condition. Computed tomography scans revealed enormous pancreatic
      abscesses expanding from the pancreatic body to the pelvic area. Pigtail
      catheters were inserted for percutaneous drainage. Even after the drainage, the
      abscesses did not improve. Percutaneous necrosectomy was performed using a
      resectoscope through a fistulous tract. After two necrosectomies, the CT scans
      showed remarkable decreases in the size of the cystic abscesses, and finally, no
      abscesses were detectable on the 117 th hospital day. CONCLUSION: We herein
      present the first description of a minimally invasive technique, using
      resectoscopy, for treating intractable pancreatic abscesses. Future studies are
      warranted to examine the efficacy and safety of this procedure for difficult
      cases, as presented in this report.

PMID- 25382169
TI  - Helicobacter pylori test-and-treat program can be cost-effective to prevent
      gastric cancer in Taiwanese adults: referred to the nationwide reimbursement
      database.
AB  - BACKGROUND: Helicobacter pylori infection increases the risk of gastric cancer.
      The study aimed to compare cost-effectiveness ratios of H. pylori test-and-treat
      programs to prevent gastric cancer in Taiwan, referring to the nationwide
      reimbursement database and expected years of life lost. MATERIALS AND METHODS:
      During 1998-2009, there were 12,857 females and 24,945 males with gastric
      adenocarcinoma in Taiwan National Cancer Registry. They were followed up to 2010
      and linked to the reimbursement database of National Health Insurance and the
      national mortality registry to determine lifetime health expenditures and
      expected years of life lost. Cost-effectiveness ratios of H. pylori test-and
      treat programs for prevention of gastric adenocarcinoma were compared between
      screenings with (13) C-urea breath test and with anti-H. pylori IgG. RESULTS: The
      test-and-treat program with anti-H. pylori IgG to prevent gastric adenocarcinoma
      had lower incremental cost-effectiveness ratios than that with (13) C-urea breath
      test in both sexes (females: 244 vs 1071 US dollars/life-year; males: 312 vs 1431
      US dollars/life-year). Cost saving would be achieved in an endemic area where H.
      pylori prevalence was >73.5%, or by selecting subpopulations with high absolute
      risk reduction rates of cancer after eradication. Moreover, expected years of
      life lost of gastric adenocarcinoma were higher and the incremental cost
      effectiveness ratios of test-and-treat programs were more cost-effective in young
      adults (30-69 y/o) than in elders (>=70 y/o). CONCLUSIONS: The test-and-treat
      program with anti-H. pylori IgG shall be cost-effective to prevent gastric
      adenocarcinoma in a high endemic area, especially beginning at 30 years of age
      when H. pylori prevalence rates become stabilized.

PMID- 25382171
TI  - Mary Seacole: global nurse extraordinaire.
AB  - AIMS: A discussion of recently discovered literature that reveals how after the
      Crimean War ended in 1856, Jamaican nurse, doctress and entrepreneur Mary Seacole
      travelled more widely and gained further international recognition than had
      previously been appreciated. BACKGROUND: New findings demonstrate that Seacole's
      international charitable and business activities were reported more widely than
      realised. Recently discovered literature uncovers her networking and strategic
      skills in various social milieus. A former Scutari nurse and 39 other women,
      offered their service to Seacole to nurse British soldiers in India. Newspapers
      also reported the medal she had been awarded from the Turkish government. DESIGN:
      Discussion paper. DATA SOURCES: Digitized 19th-century newspaper reports, and
      1857 Dutch and 1858 French translations of Seacole's autobiography and a recently
      discovered handwritten letter dated 1 October 1857 from Seacole to Sir Henry
      Storks, at the time Secretary for Military Correspondence at the War Office,
      London. IMPLICATIONS FOR NURSING: Awareness of the findings affords a more
      thorough understanding of the scope and diversity of nursing history. This can
      provide valuable role models for the 21st century generations of competent and
      self-confident healthcare professionals. The new evidence offers further
      testimony that Seacole can truly be considered as one such figurehead.
      CONCLUSIONS: British and international primary sources reveal Mary Seacole as an
      historical and charismatic global phenomenon, more than had been previously
      realised.

PMID- 25382172
TI  - Determination of metabolites of diosmetin-7-O-glucoside by a newly isolated
      Escherichia coli from human gut using UPLC-Q-TOF/MS.
AB  - Different human intestinal bacteria were isolated and screened for their ability
      to transform diosmetin-7-O-glucoside. A Gram-negative anaerobic bacterium, strain
      4, capable of metabolizing diosmetin-7-O-glucoside was newly isolated. Its 16S
      rRNA gene sequence displayed 99% similarity with that of Escherichia. Then strain
      4 was identified as a species of the genus Escherichia and was named Escherichia
      sp. 4. Additionally, an ultraperformance liquid chromatography/quadrupole-time-of
      flight mass spectrometry (UPLC-Q-TOF/MS) technique combined with Metabolynx
      software method was established to screen the metabolites of diosmetin-7-O
      glucoside. Comparing the retention time and MS/MS spectrum, three metabolites
      were detected and tentatively identified. These metabolites were acquired by four
      proposed metabolic pathways including dehydroxylation, deglycosylation,
      methylation, and acetylation. Diosmetin-7-O-glucoside was mainly bioconverted to
      considerable amounts of diosmetin and minor amounts of acacetin by the majority
      of the isolated intestinal bacteria such as Escherichia sp. 4. Subsequently,
      several strains could degrade acacetin to produce methylated and acetylated
      acacetin. The metabolites and metabolic pathways of diosmetin-7-O-glucoside by
      human intestinal bacterium Escherichia sp. 4 were first investigated. 

PMID- 25382173
TI  - Rhodium(II)-catalyzed intramolecular formal [4 + 3] cycloadditions of
      dienyltriazoles: rapid access to fused 2,5-dihydroazepines.
AB  - Rhodium(II)-catalyzed intramolecular [4 + 3] cycloadditions of dienyltriazoles
      have been developed, which enable the efficient synthesis of various fused 2,5
      dihydroazepines. Mechanistically, the titled reaction proceeds via an interesting
      tandem cyclopropanation/aza-cope rearrangement.

PMID- 25382174
TI  - Developing a multiplex mtSNP assay for forensic application in Han Chinese based
      on mtDNA phylogeny and hot spot.
AB  - We designed one multiplex assay with a reduced number of SNPs from whole
      mitochondrial genome as a screening approach for forensic purposes and developed
      a multiplex SNaPshot assay with 26 mitochondrial SNPs (mtSNPs). This assay
      included 16 target mtSNPs that defined the main haplogroups in Chinese population
      and ten hot-spot mtSNPs found by pyrosequencing. To validate our multiplex mtSNP
      assay, we not only analyzed a Chinese Han population sample, but also sequenced
      the complete control region of same set of individuals. Fifty-one haplotypes were
      observed in 204 individuals using our multiplex mtSNP assay and the haplotype
      diversity was estimated to be 0.9626. Our multiplex mtSNP assay could also
      distinguish some individuals sharing the same control region sequences. The same
      mtSNP profiles were obtained from the bloodstain, hair shaft, and salivary swab
      from same individuals. A good profile could be obtained with 50 pg of DNA. It was
      evident that our multiplex mtSNP assay not only improved the discrimination
      power, but also allowed allocating mitochondrial DNA profiles to particular
      haplogroups not clearly defined with the control region alone. We highlight the
      importance of the balance of target mtSNPs for haplogroup assignment and hot-spot
      mtSNPs for increasing discrimination power. 

PMID- 25382178
TI  - Resilience and the reliability of spectral entropy to assess ecosystem stability.

PMID- 25382179
TI  - Design of sustained release tablet containing fucoidan.
AB  - The study introduced a new therapeutic agent, fucoidan, which can offer potential
      medical treatments including anti-inflammatory and anti-coagulant activities, as
      well as anti-proliferative effects on cancer cells. Fucoidan was included in
      sustained release formulations expected for an effective plasma drug
      concentration for approximately 24 h. The matrices based on the two polymers
      hydroxypropyl methycellulose (HPMC) and polyethylene oxide (PEO) were prepared
      with various ratios between the polymers and fucoidan. The dissolution profiles
      of various matrix tablets performed in enzyme-free simulated intestinal fluid (pH
      6.8) for 24 h indicated a higher potential of PEO-based matrix tablets in
      sustaining release of fucoidan. The swelling and erosion of the tablets were also
      characterized to elucidate the difference among those dissolution profiles.

PMID- 25382180
TI  - Semi-aromatic polyesters based on a carbohydrate-derived rigid diol for
      engineering plastics.
AB  - New carbohydrate-based polyesters were prepared from isoidide-2,5-dimethanol
      (extended isoidide, XII) through melt polymerization with dimethyl esters of
      terephthalic acid (TA) and furan-2,5-dicarboxylic acid (FDCA), yielding semi
      crystalline prepolymers. Subsequent solid-state post-condensation (SSPC) gave
      high molecular weight (Mn =30 kg mol(-1) for FDCA) materials, the first examples
      of high Mn , semi-aromatic homopolyesters containing isohexide derivatives
      obtained via industrially relevant procedures. NMR spectroscopy showed that the
      stereo-configuration of XII was preserved under the applied conditions. The
      polyesters are thermally stable up to 380  degrees C. The TA- and FDCA-based
      polyesters have high Tg (105  degrees C and 94  degrees C, resp.) and Tm (284 
      degrees C and 250  degrees C, resp.) values. Its reactivity, stability, and
      ability to afford high Tg and Tm polyesters make XII a promising diol for the
      synthesis of engineering polymers. 

PMID- 25382182
TI  - Long-term alpha-tocopherol supplements may improve mental development in
      extremely low birthweight infants.
AB  - AIM: Methods to improve the mental development of extremely low birthweight
      (ELBW) children are currently lacking. We assessed the effects of long-term
      supplementation of alpha-tocopherol on the neurological development of 259 school
      aged ELBW children. METHODS: Extremely low birthweight participants were divided
      into three groups: group A with no alpha-tocopherol supplementation (n = 121);
      group B with the supplementation for <6 months (n = 104) and group C with the
      supplementation for more than 6 months (n = 34). We analysed the participants'
      data at birth and between the ages of one-and-a-half to 8 years and evaluated
      potential factors associated with intellectual disabilities. RESULTS: Children
      from group C had the best outcome. The groups' mean gestational weeks and mean
      ventilator days were as follows: 27.5 weeks, 16.1 days (group A); 25.7 weeks,
      41.7 days (group B); and 25.1 weeks, 75.5 days (group C). Multivariate regression
      analysis revealed that the odds ratios for impaired mental development at 8 years
      were 1.5 in group B and 0.19 (p = 0.017) in group C, compared with 1.0 in group
      A. The association between the duration of alpha-tocopherol administration and
      performance intelligence quotient (IQ) was dose dependent (p = 0.03). CONCLUSION:
      Long-term supplementation of alpha-tocopherol appeared to improve mental
      development, in particular, performance IQ, in school-aged ELBW children.

PMID- 25382181
TI  - The DNA-binding domain of yeast Rap1 interacts with double-stranded DNA in
      multiple binding modes.
AB  - Saccharomyces cerevisiae repressor-activator protein 1 (Rap1) is an essential
      protein involved in multiple steps of DNA regulation, as an activator in
      transcription, as a repressor at silencer elements, and as a major component of
      the shelterin-like complex at telomeres. All the known functions of Rap1 require
      the known high-affinity and specific interaction of the DNA-binding domain with
      its recognition sequences. In this work, we focus on the interaction of the DNA
      binding domain of Rap1 (Rap1(DBD)) with double-stranded DNA substrates.
      Unexpectedly, we found that while Rap1(DBD) forms a high-affinity 1:1 complex
      with its DNA recognition site, it can also form lower-affinity complexes with
      higher stoichiometries on DNA. These lower-affinity interactions are independent
      of the presence of the recognition sequence, and we propose they originate from
      the ability of Rap1(DBD) to bind to DNA in two different binding modes. In one
      high-affinity binding mode, Rap1(DBD) likely binds in the conformation observed
      in the available crystal structures. In the other alternative lower-affinity
      binding mode, we propose that a single Myb-like domain of the Rap1(DBD) makes
      interactions with DNA, allowing for more than one protein molecule to bind to the
      DNA substrates. Our findings suggest that the Rap1(DBD) does not simply target
      the protein to its recognition sequence but rather it might be a possible point
      of regulation. 

PMID- 25382183
TI  - Phosphatase Wip1 as a new therapeutic target for intestinal ischemia-reperfusion
      injury.
AB  - Intestinal ischemia/reperfusion (I/R) injury is a pathophysiology involving local
      tissue injury and organ dysfunction. Accumulating evidence has confirmed that the
      infiltration of neutrophils is of central importance in mediating intestinal I/R
      injury. On the other hand, adequate neutrophils in the intestine could also
      benefit the antibacterial translocation and tissue repair. Consequently,
      regulation of neutrophil immunity after intestinal I/R might be a promising
      therapy for controlling intestinal injury. Wip1 is a serine/threonine protein
      phosphatase that acts as the master regulator of tumorigenesis. However, emerging
      evidence highlights the importance of Wip1 in regulating neutrophil development,
      maturation, migration and neutrophil pro-inflammatory cytokine productions. Our
      recent studies showed that Wip1 negatively regulates neutrophil inflammatory
      responses and plays a protective role in intestinal I/R injury. In light of this
      discovery, we believe that Wip1 might be a new therapeutic target for treating
      intestinal I/R injury. 

PMID- 25382184
TI  - Retinal damage and vision loss in African American multiple sclerosis patients.
AB  - OBJECTIVE: To determine whether African American (AA) multiple sclerosis (MS)
      patients exhibit more retinal damage and visual impairment compared to Caucasian
      American (CA) MS patients. METHODS: A total of 687 MS patients (81 AAs) and 110
      healthy control (HC) subjects (14 AAs) were recruited at 3 academic hospitals
      between 2008 and 2012. Using mixed effects regression models, we compared high-
      and low-contrast visual acuity (HCVA and LCVA) and high-definition spectral
      domain optical coherence tomography measures of retinal architecture between MS
      patients of self-identified AA and CA ancestry. RESULTS: In HCs, baseline
      peripapillary retinal nerve fiber layer (RNFL) thickness was 6.1um greater in AAs
      (p = 0.047), whereas ganglion cell/inner plexiform layer (GCIP) thickness did not
      differ by race. In MS patients, baseline RNFL did not differ by race, and GCIP
      was 3.98um thinner in AAs (p = 0.004). AAs had faster RNFL and GCIP thinning
      rates compared to CAs (p = 0.004 and p = 0.046, respectively). AA MS patients had
      lower baseline HCVA (p = 0.02) and worse LCVA per year of disease duration (p =
      0.039). Among patients with an acute optic neuritis (AON) history, AAs had
      greater loss of HCVA than CA patients (p = 0.012). INTERPRETATION: This
      multicenter investigation provides objective evidence that AA MS patients exhibit
      accelerated retinal damage compared to CA MS patients. Self-identified AA
      ancestry is associated with worse MS-related visual disability, particularly in
      the context of an AON history, suggesting a more aggressive inflammatory disease
      course among AA MS patients or a subpopulation therein.

PMID- 25382185
TI  - Higher HDL cholesterol is associated with better cognitive function: the Maine
      Syracuse study.
AB  - Few studies have examined associations between different subcategories of
      cholesterol and cognitive function. We examined relationships between total
      cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density
      lipoprotein cholesterol (LDL), triglyceride levels and cognitive performance in
      the Maine-Syracuse Longitudinal Study, a community-based study of cardiovascular
      risk factors. Cross-sectional analyses were undertaken on data from 540
      participants, aged 60 to 98 years, free of dementia and stroke. TC, HDL, LDL, and
      triglyceride levels were obtained. Cognitive function was assessed using a
      thorough neuropsychological test battery, including domains of cognitive function
      indexed by multiple cognitive tests. The cognitive outcomes studied were as
      follows: Visual-Spatial Memory and Organization, Verbal and Working Memory,
      Scanning and Tracking, Abstract Reasoning, a Global Composite score, and the Mini
      Mental State Examination (MMSE). Significant positive associations were observed
      between HDL-cholesterol and the Global Composite score, Working Memory, and the
      MMSE after adjustment for demographic and cardiovascular risk factors.
      Participants with desirable levels of HDL (>=60 mg/dL) had the highest scores on
      all cognitive outcomes. There were no significant associations observed between
      TC, LDL, or triglyceride concentrations and cognition. In older individuals, HDL
      cholesterol was related to a composite of Working Memory tests and for general
      measures of cognitive ability when adjusted for cardiovascular variables. We
      speculate that persons over 60 are survivors and thus less likely to show
      cognitive deficit in relation to TC, LDL-cholesterol, and triglycerides.
      Longitudinal studies are needed to examine relations between specific cognitive
      abilities and the different subcategories of cholesterol.

PMID- 25382186
TI  - Photoluminescence mechanisms of metallic Zn nanospheres, semiconducting ZnO
      nanoballoons, and metal-semiconductor Zn/ZnO nanospheres.
AB  - We utilized a thermal radiation method to synthesize semiconducting hollow ZnO
      nanoballoons and metal-semiconductor concentric solid Zn/ZnO nanospheres from
      metallic solid Zn nanospheres. The chemical properties, crystalline structures,
      and photoluminescence mechanisms for the metallic solid Zn nanospheres,
      semiconducting hollow ZnO nanoballoons, and metal-semiconductor concentric solid
      Zn/ZnO nanospheres are presented. The PL emissions of the metallic Zn solid
      nanospheres are mainly dependent on the electron transitions between the Fermi
      level (E(F)) and the 3d band, while those of the semiconducting hollow ZnO
      nanoballoons are ascribed to the near band edge (NBE) and deep level electron
      transitions. The PL emissions of the metal-semiconductor concentric solid Zn/ZnO
      nanospheres are attributed to the electron transitions across the metal
      semiconductor junction, from the E(F) to the valence and 3d bands, and from the
      interface states to the valence band. All three nanostructures are excellent room
      temperature light emitters.

PMID- 25382187
TI  - The transmembrane protein Sho1 cooperates with the mucin Msb2 to regulate
      invasive growth and plant infection in Fusarium oxysporum.
AB  - In the vascular wilt pathogen Fusarium oxysporum, the mitogen-activated protein
      kinase (MAPK) Fmk1 is essential for plant infection. The mucin-like membrane
      protein Msb2 regulates a subset of Fmk1-dependent functions. Here, we examined
      the role of the tetraspan transmembrane protein Sho1 as an additional regulator
      of the Fmk1 pathway and determined its genetic interaction with Msb2. Targeted
      Deltasho1 mutants were generated in wild-type and Deltamsb2 backgrounds to test
      possible interactions between the two genes. The mutants were examined for hyphal
      growth under different stress conditions, phosphorylation of the MAPK Fmk1 and an
      array of Fmk1-dependent virulence functions. Similar to Msb2, Sho1 was required
      for the activation of Fmk1 phosphorylation, as well as Fmk1-dependent gene
      expression and invasive growth functions, including extracellular pectinolytic
      activity, cellophane penetration, plant tissue colonization and virulence on
      tomato plants. Deltasho1 mutants were hypersensitive to the cell wall-perturbing
      compound Calcofluor White, and this phenotype was exacerbated in the Deltamsb2
      Deltasho1 double mutant. These results highlight that Sho1 and Msb2 have
      partially overlapping functions upstream of the Fmk1 MAPK cascade, to promote
      invasive growth and plant infection, as well as cell wall integrity, in F.
      oxysporum.

PMID- 25382188
TI  - A novel trial of topotecan, ifosfamide, and carboplatin (TIC) in children with
      recurrent solid tumors.
AB  - BACKGROUND: Ifosfamide, carboplatin, and etoposide (ICE) in children with
      refractory or recurrent solid tumors and lymphomas has resulted in good overall
      response rates (ORR). Etoposide, a topoisomerase-II inhibitor, however, has been
      associated with a significant increase in secondary leukemia. The rationale for
      substituting topotecan, a topoisomerase-I inhibitor, for etoposide in this
      regimen, a topoisomerase-II inhibitor, includes its limited toxicity profile and
      decreased leukemogenicity. Furthermore, topotecan in combination with both
      alkylators and platinating agents are additive and/or synergistic against a
      variety of solid tumors. PROCEDURE: Patients with relapsed/refractory solid
      tumors received ifosfamide (9 g/m2 ) and carboplatin (area under the curve: 3
      mg/ml/min). Topotecan was also administered at 0.5 mg/m2 /day * 3 days (N = 12)
      and in a small cohort (N = 3) at 0.75 mg/m2 /day. RESULTS: Fifteen patients were
      entered onto study. Two patients developed seizures/encephalitis secondary to
      ifosfamide. One patient had dose-limiting thrombocytopenia secondary to TIC that
      resolved with supportive care. Patients received a median of three cycles (1-3)
      of TIC. Of the 14 evaluable patients for response, 4/14 had a complete response
      (CR), 2/14 had a partial response (PR), and 1/14 patients had stable disease
      (SD). The ORR (CR + PR) was 43%. CONCLUSION: TIC chemotherapy is feasible and
      tolerable in children and adolescents with refractory/recurrent solid tumors and
      lymphomas and results in a 43% excellent ORR in this poor-risk group of patients.
      A larger cohort of patients, especially in Wilms tumor and central nervous system
      (CNS) tumors, should be studied in the future to attempt to confirm these
      preliminary findings. Pediatr Blood Cancer 2015;62:274-278. (c) 2014 Wiley
      Periodicals, Inc.

PMID- 25382189
TI  - Modulation of signaling enhances the efficacy of the combination of satraplatin
      and erlotinib.
AB  - The active metabolite (JM118) of the oral platinum analog satraplatin (JM216) was
      investigated for potential synergism with erlotinib, an epidermal growth factor
      receptor (EGFR) inhibitor. JM118 sensitivity of 7 cancer cell lines (ovarian:
      2008, A2780; colon: Lovo92, WiDr; lung: A549, SW1573; epidermoid: A431), was
      enhanced most pronounced when JM118 preceded erlotinib, which was associated with
      increased formation of DNA-platinum adducts. The combination increased G2/M phase
      accumulation and enhanced apoptosis. JM118 increased the phosphorylation of the
      cell cycle proteins CDK2 and CHK1 after 24 hr exposure. JM118/erlotinib enhanced
      Erk and Akt phosphorylation after 2 hr. JM118 significantly decreased the
      phosphorylation of PTEN, VEGFR, EPHA1, ERBB4, FGF-R, andSTAT3 by 20 (PTEN) to
      >90% (STAT3). CONCLUSION: Erlotinib enhanced the effects of JM118, even in cells
      with mutations in Ras. The mechanism of synergy involved a combination of effects
      on platinum-DNA adduct formation, cell cycle distribution and signaling.

PMID- 25382190
TI  - Targeting c-MET/HGF signaling pathway in upper gastrointestinal cancers:
      rationale and progress.
AB  - Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be
      associated with cell proliferation, invasion, metastasis and poor-prognosis in
      several tumor types, including upper gastrointestinal-malignancies. The
      interaction of c-Met with multiple signalling-pathways involved in tumorigenic
      properties and invasive-phenotype has gained substantial attention, suggesting
      its role as an intriguing-target for cancer-therapy. In recent years, there have
      been considerable efforts in the development of effective c-Met inhibitors with
      potential clinical-applications and one of them, crizotinib (dual c-Met/ALK
      inhibitor), has recently been approved for lung-cancers with ALKrearrangement.
      However several important questions remain to be answered on the molecular
      mechanisms underlying the antitumor effects of crizotinib, as well as on its
      possible role in the treatment of different tumor types, including
      uppergastrointestinal- cancers. The aim of this review is to give an overview on
      critical role of the c-Met/HGF pathway in cancer, and the preclinical/clinical
      studies on c-Met inhibitors. There are accumulating evidences on therapeutic
      potential of c-Met inhibitors for the treatment of other malignancies, such as
      gastric and pancreatic cancers. However, further investigations are needed to
      identify determinants of the activity of c-Met inhibitors, through the analysis
      of genetic/ environmental alterations affecting c-Met and parallel pro-cancer
      pathways; mechanisms result in developing resistance to anti-c-Met agents; and
      selection of patients that might benefit from therapy. These studies will be
      essential to improve the selectivity/efficacy of future anticancer strategies of
      c-Met targeted-therapies in the treatment of upper gastrointestinal- cancers. 

PMID- 25382191
TI  - New strategies and applications for drugs targeting EGFR and c-Met.

PMID- 25382192
TI  - P-modified and carbon shell coated Co nanoparticles for efficient alkaline oxygen
      reduction catalysis.
AB  - Described herein is the development of a novel Co-based oxygen electrode catalyst
      coupled with unique carbon structures. The present carbon shell coated Co
      nanoparticles of which the surface composites are modified by phosphorus
      incorporation, exhibit efficient oxygen reduction activities as well as oxygen
      evolving properties. 

PMID- 25382193
TI  - Different neural and cognitive response to emotional faces in healthy monozygotic
      twins at risk of depression.
AB  - BACKGROUND: Negative cognitive bias and aberrant neural processing of emotional
      faces are trait-marks of depression. Yet it is unclear whether these changes
      constitute an endophenotype for depression and are also present in healthy
      individuals with hereditary risk for depression. METHOD: Thirty healthy, never
      depressed monozygotic (MZ) twins with a co-twin history of depression (high risk
      group: n = 13) or without co-twin history of depression (low-risk group: n = 17)
      were enrolled in a functional magnetic resonance imaging (fMRI) study. During
      fMRI, participants viewed fearful and happy faces while performing a gender
      discrimination task. After the scan, they were given a faces dot-probe task, a
      facial expression recognition task and questionnaires assessing mood, personality
      traits and coping strategies. RESULTS: High-risk twins showed increased neural
      response to happy and fearful faces in dorsal anterior cingulate cortex (ACC),
      dorsomedial prefrontal cortex (dmPFC), pre-supplementary motor area and occipito
      parietal regions compared to low-risk twins. They also displayed stronger
      negative coupling between amygdala and pregenual ACC, dmPFC and temporo-parietal
      regions during emotional face processing. These task-related changes in neural
      responses in high-risk twins were accompanied by impaired gender discrimination
      performance during face processing. They also displayed increased attention
      vigilance for fearful faces and were slower at recognizing facial expressions
      relative to low-risk controls. These effects occurred in the absence of
      differences between groups in mood, subjective state or coping. CONCLUSIONS:
      Different neural response and functional connectivity within fronto-limbic and
      occipito-parietal regions during emotional face processing and enhanced fear
      vigilance may be key endophenotypes for depression.

PMID- 25382194
TI  - A Ten-Year Molecular Survey on Parvoviruses Infecting Carnivores in Bulgaria.
AB  - Parvoviruses represent the most important infectious agents that are responsible
      for severe to fatal disease in carnivores. This study reports the results of a 10
      year molecular survey conducted on carnivores in Bulgaria (n = 344), including
      262 dogs and 19 cats with gastroenteritis, and 57 hunted wild carnivores. Real
      time polymerase chain reaction (qPCR), followed by virus characterization by
      minor groove binder (MGB) probe assays, detected 216 parvovirus positive dogs
      with a predominance of canine parvovirus type 2a (CPV-2a, 79.17%) over CPV-2b
      (18.52%) and CPV-2c (2.31%). Rottweilers and German shepherds were the most
      frequent breeds among CPV-positive pedigree dogs (n = 96). Eighteen cats were
      found to shed parvoviruses in their faeces, with most strains being characterized
      as FPLV (n = 17), although a single specimen tested positive for CPV-2a. Only two
      wild carnivores were parvovirus positive, a wolf (Canis lupus) and a red fox
      (Vulpes vulpes), both being infected by CPV-2a strains. 

PMID- 25382195
TI  - An electrochemical and computational study for discrimination of D- and L-cystine
      by reduced graphene oxide/beta-cyclodextrin.
AB  - Here, we report a novel enantioselective electrochemical biosensor for the
      discrimination of cystine enantiomers (d- and l-cystine) using a chiral interface
      for the specific recognition of d- and l-cystine. The biosensor is based on
      reduced graphene oxide modified by beta-cyclodextrin (rGO/beta-CD) at the GCE
      surface. During the preparation of rGO/beta-CD/GCE, the modified electrode
      surfaces were characterized by cyclic voltammetry (CV), electrochemical impedance
      spectroscopy (EIS) and scanning electron microscopy (SEM). The electrochemical
      behaviours of the d- and l-cystine were investigated using the rGO/beta-CD/GCE by
      CV and compared to bare GCE. A clear separation between the oxidation peak
      potentials of d- and l-cystine was observed at 1.32 and 1.42 V, respectively. The
      electrochemical discrimination performance of the fabricated chiral sensor was
      also examined by differential pulse voltammetry (DPV) in a mixed solution of d-
      and l-cystine. In addition, the DPV technique was used for the determination of d
      and l-cystine at low concentration values in the range of 1.0-10.0 MUM. To
      investigate the amperometric response of rGO/beta-CD/GCE towards d- and l
      cystine, the chronoamperometry technique was used in the concentration range of
      10.0-100.0 MUM. The interactions of the enantiomers with rGO/beta-CD were
      modelled by molecular docking using AutoDock Vina, and the interaction energies
      were predicted to be -4.8 and -5.3 kcal mol(-1) for d- and l-cystine,
      respectively. The corresponding values of binding constants were calculated to be
      3.32 * 10(3) and 7.71 * 10(3) M(-1), respectively. The experimental and molecular
      docking results indicate that the rGO/beta-CD/GCE has a different affinity for
      each enantiomer. 

PMID- 25382196
TI  - Predicting subtypes of thymic epithelial tumors using CT: new perspective based
      on a comprehensive analysis of 216 patients.
AB  - It is highly necessary to identify low versus high risk thymic epithelial tumors
      (TETs) before operation to guide optimal treatment strategies. Current CT
      diagnostic parameters could not effectively achieve this goal. We evaluated three
      parameters of CT scan in a cohort of 216 TETs patients. Parameters of contrast
      enhancement, risk of aggressiveness, and nodule with fibrous septum were
      evaluated in low (A, AB) versus high risk (B1, B2, B3 and thymic carcinoma) TETs.
      Grade of contrast enhancement showed predictive value in classifying low and high
      risk TETs well. A maximal contrast-enhanced range of 25.5 HU could produce 78.8%
      sensitivity and 68.5% specificity in determining low risk subtypes. Additionally,
      risk of aggressiveness parameter was demonstrated to be associated with TETs
      subtype (r = 0.801, P < 0.001) and may add confidence in determining low versus
      high risk subtypes. Furthermore, multiple nodule with fibrous septum could
      suggest subtype AB. Findings from this study support role of studied parameters
      of CT manifestations in predicting the low and high risk stages of TETs. These
      findings provide empirical evidence for incorporating these parameters in
      clinical practice for identifying TETs stage before operation, if validated in
      additional studies. 

PMID- 25382197
TI  - Xenotransplantation literature update, September-October 2014.

PMID- 25382198
TI  - Cyanobacteria as photosynthetic biocatalysts: a systems biology perspective.
AB  - The increasing need to replace oil-based products and to address global climate
      change concerns has triggered considerable interest in photosynthetic
      microorganisms. Cyanobacteria, in particular, have great potential as
      biocatalysts for fuels and fine-chemicals. During the last few years the
      biotechnological applications of cyanobacteria have experienced an unprecedented
      increase and the use of these photosynthetic organisms for chemical production is
      becoming a tangible reality. However, the field is still immature and many
      concerns about the economic feasibility of the biotechnological potential of
      cyanobacteria remain. In this review we describe recent successes in biofuel and
      fine-chemical production using cyanobacteria. We discuss the role of the
      photosynthetic metabolism and highlight the need for systems-level metabolic
      optimization in order to achieve the true potential of cyanobacterial
      biocatalysts. 

PMID- 25382199
TI  - Young onset dementia--what does the name imply?

PMID- 25382200
TI  - Commentary on: Amnestic mild cognitive impairment and incident dementia and
      Alzheimer's disease in geriatric depression.

PMID- 25382202
TI  - Impact of a stereocentre inversion in cyclic lipodepsipeptides from the viscosin
      group: a comparative study of the viscosinamide and pseudodesmin conformation and
      self-assembly.
AB  - The viscosin group covers a series of cyclic lipodepsipeptides (CLPs) produced by
      Pseudomonas bacteria, with a range of biological functions and antimicrobial
      activities. Their oligopeptide moieties are composed of both L- and D-amino
      acids. Remarkably, the Leu5 amino acid-centrally located in the nonapeptide
      sequence-is the sole residue found to possess either an L or D configuration,
      depending on the producing strain. The impact of this D/L switch on the solution
      conformation was investigated by NMR-restrained molecular modelling of the
      epimers pseudodesmin A and viscosinamide A. Although the backbone fold remained
      unaffected, the D/L switch adjusted the segregation between hydrophobic and
      hydrophilic residues, and thus the amphipathicity. It also influenced the self
      assembly capacity in organic solvents. Additionally, several new minor variants
      of viscosinamide A from Pseudomonas fluorescens DR54 were identified, and an NMR
      assay is proposed to assess the presence of either an L- or D-Leu5. 

PMID- 25382201
TI  - Quantifying lipid contents in enveloped virus particles with plasmonic
      nanoparticles.
AB  - Phosphatidylserine (PS) and monosialotetrahexosylganglioside (GM1 ) are examples
      of two host-derived lipids in the membrane of enveloped virus particles that are
      known to contribute to virus attachment, uptake, and ultimately dissemination. A
      quantitative characterization of their contribution to the functionality of the
      virus requires information about their relative concentrations in the viral
      membrane. Here, a gold nanoparticle (NP) binding assay for probing relative PS
      and GM1 lipid concentrations in the outer leaflet of different HIV-1 and Ebola
      virus-like particles (VLPs) using sample sizes of less than 3 * 10(6) particles
      is introduced. The assay evaluates both scattering intensity and resonance
      wavelength, and determines relative NP densities through plasmon coupling as a
      measure for the target lipid concentrations in the NP-labeled VLP membrane. A
      correlation of the optical observables with absolute lipid contents is achieved
      by calibration of the plasmon coupling-based methodology with unilamellar
      liposomes of known PS or GM1 concentration. The performed studies reveal
      significant differences in the membrane of VLPs that assemble at different
      intracellular sites and pave the way to an optical quantification of lipid
      concentration in virus particles at physiological titers. 

PMID- 25382203
TI  - Clinical pharmacology of EGFR/Met inhibitors in non-small cell lung cancer.
AB  - Development of molecular targeting agents, starting with imatinib for chronic
      myeloid leukemia or gefitinib for non-small cell lung cancer (NSCLC), has
      recently progressed at a rapid rate. Epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs) have already been developed to the 2nd and 3rd
      generation, and novel drug development targeted towards Met activation, which is
      an EGFR-TKI resistance mechanism, is ongoing. Although the era of new anticancer
      agents is moving towards an era of molecular targeting agents, the methods used
      for drug development are not different than before. In addition to the importance
      of pharmacokinetics (PK) and pharmacodynamics (PD) for drug development, emerging
      evidence is also demonstrating the significance of pharmacogenomics, since
      certain types of gene alteration may greatly affect drug metabolism, excretion,
      and notably, clinical efficacy. It is desirable to determine optimal doses of
      anticancer drugs by taking into account these factors that could potentially
      influence PK/PD. The following article reviews the clinical development of
      EGFR/Met inhibitors for NSCLC and the clinical pharmacology of these drugs.

PMID- 25382204
TI  - Targeting the Ataxia Telangiectasia Mutated Protein in Cancer Therapy.
AB  - Genotoxic anticancer drugs explicate their effects damaging DNA, thus triggering
      a coordinated signal-transduction network called DNA Damage Response (DDR).
      Ataxia Telangiectasia Mutated (ATM) protein plays a central role in this
      response: activated by DNA damage, ATM phosphorylates itself and downstream
      effectors that arrest cell cycle allowing for DNA repair or, should DNA damage be
      too severe and not retrievable, inducing apoptosis. ATM is a worth-investigating
      target for tumor radio- and chemosensitization. During last years, pharmaceutical
      industries and research laboratories have developed a series of small molecules,
      capable to inhibit ATM with increasing specificity. Several preclinical studies
      have demonstrated that these inhibitors alone or in association with other
      treatments may improve therapeutic outcomes. In this review we discuss ATM
      inhibitors so far developed, focussing on recent acquisitions on their potential
      antineoplastic usefulness. 

PMID- 25382205
TI  - Update on the role of neutrophils in atherosclerotic plaque vulnerability.
AB  - Atherosclerosis is the main pathophysiological process underlying acute
      cardiovascular diseases. Life-threatening conditions, such as myocardial
      infarction and ischemic stroke, are provoked by the sudden rupture of vulnerable
      atherosclerotic plaques, characterized by thin, highly inflamed and collagen-poor
      fibrous cap. Whereas both innate and adaptive inflammation progressively emerged
      as driving force of this processes, less is known about the involvement of
      neutrophils (PMNs). Advances in laboratory techniques during the last two decades
      disclosed that PMNs play a crucial role in promoting plaque vulnerability by the
      release of different enzymes, such as gelatinases (matrix metalloproteinases)
      collagenases, elastase and myeloperoxidase. Accordingly, circulating levels of
      PMNs and their products have been investigated as potential markers of plaque
      instability in both primary and secondary prevention on cardiovascular diseases.
      In addition, the development of different classes of drugs targeting PMNs
      activation is emerging as an interesting field of research. This narrative review
      will provide an update on the role of PMNs in promoting plaque vulnerability also
      discussing the potential effects of therapeutic strategies targeting PMN on
      plaque vulnerability. 

PMID- 25382206
TI  - The role of adipocytokines in atherogenesis and atheroprogression.
AB  - Research investigations on adipose tissue were focused for several decades on its
      "storage" function. Emerging evidence unveiled adipose tissue as an endocrine
      organ releasing a several mediators termed as adipokines. Adipokine-mediated
      functions include both physiological and pathophysiological roles such as
      regulation of energy metabolism, immune response and vascular homeostasis, as
      well as inflammatory and metabolic diseases (i.e. atherogenesis, diabetes and
      obesity clustered in the concept of metabolic syndrome). A dysregulation of
      adipokine levels has been also suggested as a potential common mechanism
      underlying these disorders. For instance, an unbalance between pro- and anti
      inflammatory adipokines was positively associated with traditional risk factors
      (dyslipidaemia, hypertension, insulin resistance) in obesity, diabetes and
      atherogenesis. Adipokine-mediated activities particularly affected endothelial
      dysfunction/activation and intraplaque inflammation/vulnerability. The purpose of
      this narrative review is to provide an overview on the role of adipokines in
      atherogenesis. Evidence from basic research studies about adipokine-induced
      regulation of vascular and immune cell subsets will be discussed. Finally,
      conflicting results from clinical trials we be reported, with an attempt to
      better understand the reason why promising basic research results did not allow a
      speedy "into human" translation for clinical management of atherogenesis. 

PMID- 25382207
TI  - Prevention and therapeutic strategies of thromboembolic events in patients with
      inflammatory bowel diseases: a report of three cases.
AB  - Crohn's disease and ulcerative colitis belong to a group of inflammatory bowel
      diseases (IBD). IBD are characterized by a chronic character of inflammatory
      process and overlapping immunological abnormalities, which, along with
      therapeutic strategies are currently available, underlie an increased risk of
      venous thromboembolic events (VTE). The most common sites of VTE in IBD patients
      are deep venous thrombosis (DVT) and pulmonary embolism (PE). These complications
      are particularly important in clinical practice due to a very high mortality
      rate. Therefore, an early diagnosis of new IBD cases and the control of
      inflammatory process are thought to play a crucial role in risk reduction for
      thromboembolic events. Despite considerable evidence supporting the association
      between IBD and VTE, there is still a lack of recognition of this risk, with
      dangerous consequences for patients. In this paper authors report three cases of
      VTE in IBD patients and discuss the most relevant clinical studies found in
      MEDLINE, Cochrane Library and EMBASE regarding its prevention and management. 

PMID- 25382208
TI  - Beyond RAS: the role of epidermal growth factor receptor (EGFR) and its network
      in the prediction of clinical outcome during anti-EGFR treatment in colorectal
      cancer patients.
AB  - Although the extended RAS analysis allows a better identification of patients
      potentially candidates to anti-EGFR monoclonal antibodies, a significant
      proportion of tumours may still reveals refractory to such a treatment approach.
      In these latter cases patients are then exposed to unnecessary toxicities without
      clinical benefit. Among many further biological factors that may have a role in
      determining resistance/sensitivity to EGFR-inhibitors, the EGFR itself, other
      members of the HER family (i.e. HER-2 and HER-3) as well as other surface
      receptors such as the IGF-1 receptor seem of particular interest. Preclinical
      models have shown that these receptors are biologically connected to each other
      and able to directly or indirectly influence the downstream molecular pathways.
      In the presence of abnormal expression of these biological determinants,
      intracellular pathways may become independent from the receptor-targeting
      treatment thus making therapies directed against the receptor ineffective.
      Clinical observations and translational studies seem to confirm these findings.
      The Authors have reviewed the literature and have selected recent clinical
      reports focusing on translational research on the EGFR itself or on other
      molecules that may interfere with this pathway. We also discuss potential future
      developments in this area.

PMID- 25382210
TI  - Sub-10 nm features obtained from directed self-assembly of semicrystalline
      polycarbosilane-based block copolymer thin films.
AB  - Highly-ordered arrays with sub-10 nm features are produced with topographical
      directed self-assembly of low-molecular-weight poly(1,1-dimethyl silacyclobutane)
      block-poly(methyl methacrylate). This system turns out to be of high interest for
      lithographic applications since the domain orientation is solely controlled
      through the polymer layer thickness, while the promotion of the microphase
      separation is obtained by a short thermal annealing process under mild
      conditions. 

PMID- 25382209
TI  - Proteomic Profiling of a Biomimetic Drug Delivery Platform.
AB  - Current delivery platforms are typically designed for prolonged circulation that
      favors superior accumulation of the payload in the targeted tissue. The design of
      efficient surface modifications determines both a longer circulation time and
      targeting abilities of particles. The optimization of synthesis protocols to
      efficiently combine targeting molecules and elements that allow for an increased
      circulation time can be challenging and almost impossible when several functional
      elements are needed. On the other hand, in the last decade, the development of
      bioinspired technologies was proposed as a new approach with which to increase
      particle safety, biocompatibility and targeting, while maintaining the synthesis
      protocols simple and reproducible. Recently, we developed a new drug delivery
      system inspired by the biology of immune cells called leukolike vector (LLV) and
      formed by a nanoporous silicon core and a shell derived from the leucocyte cell
      membrane. The goal of this study is to investigate the protein content of the
      LLV. Here we report the proteomic profiling of the LLV and demonstrate that our
      approach can be used to modify the surface of synthetic particles with more than
      150 leukocyte membrane associated proteins that determine particle safety,
      circulation time and targeting abilities towards inflamed endothelium.

PMID- 25382211
TI  - The relationship between circulating irisin levels and endothelial function in
      lean and obese subjects.
AB  - OBJECTIVE: Irisin has been shown to turn white adipocytes into brown-like
      adipocytes, which is emerging as an appealing therapeutic target for obesity. The
      objective of the study was to determine whether circulating irisin levels are
      related to endothelial dysfunction in obese subjects. DESIGN: A total of 41
      nonhypertensive, nondiabetic obese subjects and 40 age- and sex-matched lean
      healthy control were involved in this study. Clinical characteristics, blood
      biochemistry, circulating irisin and adiponectin of the subjects were measured.
      Endothelium-dependent vasodilation (EDV) and endothelial-independent vasodilation
      (EIV) were determined using high-resolution ultrasound. RESULTS: Circulating
      irisin and adiponectin were significantly lower in obese subjects compared with
      lean healthy control (P < 0.05). Endothelial function was impaired in obese
      subjects (maximum EDV: 8.95 +/- 3.46% vs 14.56 +/- 3.90%, P < 0.05). Bivariate
      correlation analysis revealed that circulating irisin was positively correlated
      with EDV(r = 0.388, P < 0.01) and negatively correlated with BMI (r = -0.281, P <
      0.05), waist circumference (r = -0.298, P < 0.01), free fatty acid (FFA) (r = 
      0.289, P < 0.01), high-sensitivity C-reactive protein (hs-CRP) (r = -0.244, P <
      0.05) and malondialdehyde (r = -0.258, P < 0.05). Multiple regression analysis
      revealed that circulating irisin, adiponectin, FFA and BMI were independently
      associated with EDV after adjusting for covariates (R(2) = 0.457, F = 8.766, P =
      0.000). CONCLUSIONS: Circulating irisin level was decreased in nonhypertensive,
      nondiabetic obese subjects compared with lean healthy control. Lower levels of
      irisin are independently associated with endothelial dysfunction. Therefore,
      irisin may be involved in the regulation of endothelial function in obesity.

PMID- 25382213
TI  - High density micro-pyramids with silicon nanowire array for photovoltaic
      applications.
AB  - We use a metal assisted chemical etch process to fabricate silicon nanowire
      arrays (SiNWAs) onto a dense periodic array of pyramids that are formed using an
      alkaline etch masked with an oxide layer. The hybrid micro-nano structure acts as
      an anti-reflective coating with experimental reflectivity below 1% over the
      visible and near-infrared spectral regions. This represents an improvement of up
      to 11 and 14 times compared to the pyramid array and SiNWAs on bulk,
      respectively. In addition to the experimental work, we optically simulate the
      hybrid structure using a commercial finite difference time domain package. The
      results of the optical simulations support our experimental work, illustrating a
      reduced reflectivity in the hybrid structure. The nanowire array increases the
      absorbed carrier density within the pyramid by providing a guided transition of
      the refractive index along the light path from air into the silicon. Furthermore,
      electrical simulations which take into account surface and Auger recombination
      show an efficiency increase for the hybrid structure of 56% over bulk, 11% over
      pyramid array and 8.5% over SiNWAs. 

PMID- 25382212
TI  - Echinostoma caproni (Trematoda): differential in vivo mucin expression and
      glycosylation in high- and low-compatible hosts.
AB  - Enhanced mucus production and release appears to be a common mechanism for the
      clearance of intestinal helminths, and this expulsion is normally mediated by Th2
      type immune responses. To investigate the factors determining the expulsion of
      intestinal helminths, we have analysed in vivo expression of mucin genes at the
      site of infection in two host species displaying different compatibility with
      Echinostoma caproni (Trematoda). Surprisingly, a general down-regulation on mucin
      mRNA expression was detected in low-compatible hosts (rats) coinciding with the
      development of Th2/Th17 responses and the early rejection of the worms from the
      intestinal lumen. This suggests the existence of a mechanism by which the
      parasites can modulate the mucus barrier to favour their survival. In highly
      compatible hosts (mice), some mucin genes were found to be up-regulated
      throughout the infection, probably, to protect the intestinal epithelium against
      the infection-induced inflammation developed in this host species. Moreover,
      infection-induced changes on mucin glycans were also studied by lectin
      histochemistry. Similar alterations were detected in the ileum of infected mice
      and rats, except with SNA lectin, indicating that sylated mucins might play an
      important role in determining the evolution of the infection in each host
      species. 

PMID- 25382214
TI  - Programmable energy landscapes for kinetic control of DNA strand displacement.
AB  - DNA is used to construct synthetic systems that sense, actuate, move and compute.
      The operation of many dynamic DNA devices depends on toehold-mediated strand
      displacement, by which one DNA strand displaces another from a duplex. Kinetic
      control of strand displacement is particularly important in autonomous molecular
      machinery and molecular computation, in which non-equilibrium systems are
      controlled through rates of competing processes. Here, we introduce a new method
      based on the creation of mismatched base pairs as kinetic barriers to strand
      displacement. Reaction rate constants can be tuned across three orders of
      magnitude by altering the position of such a defect without significantly
      changing the stabilities of reactants or products. By modelling reaction free
      energy landscapes, we explore the mechanistic basis of this control mechanism. We
      also demonstrate that oxDNA, a coarse-grained model of DNA, is capable of
      accurately predicting and explaining the impact of mismatches on displacement
      kinetics. 

PMID- 25382215
TI  - Factors associated with community reintegration in the first year after stroke: a
      qualitative meta-synthesis.
AB  - PURPOSE: Although acute stroke care has improved survival, many individuals
      report dissatisfaction with community reintegration after stroke. The aim of this
      qualitative meta-synthesis was to examine the barriers and facilitators of
      community reintegration in the first year after stroke from the perspective of
      people with stroke. METHODS: A systematic literature search was conducted. Papers
      that used qualitative methods to explore the experiences of individuals with
      stroke around community reintegration in the first year after stroke were
      included. Two reviewers independently assessed the methodological quality of
      papers. Themes, concepts and interpretations were extracted from each study,
      compared and meta-synthesised. RESULTS: From the 18 included qualitative studies
      four themes related to community reintegration in the first year after stroke
      were identified: (i) the primary effects of stroke, (ii) personal factors, (iii)
      social factors and (iv) relationships with professionals. CONCLUSIONS: This
      review suggests that an individual's perseverance, adaptability and ability to
      overcome emotional challenges can facilitate reintegration into the community
      despite persisting effects of their stroke. Appropriate support from family,
      friends, the broader community and healthcare professionals is important.
      Therapeutic activities should relate to meaningful activities and should be
      tailored to the individual stroke survivor. IMPLICATIONS FOR REHABILITATION:
      Stroke survivors feel that rehabilitation in familiar environments and
      therapeutic activities that reflect real-life could help their community re
      integration. In addition to the physical sequelae of stroke, emotional
      consequences of stroke should be addressed during rehabilitation. Healthcare
      professionals can provide clear and locally relevant advice to facilitate aspects
      of community reintegration, including the return to driving and work.

PMID- 25382216
TI  - Reliability, validity, and responsiveness of the Persian version of Shoulder
      Activity Scale in a group of patients with shoulder disorders.
AB  - PURPOSE: The aim of this methodological study was to cross-culturally translate
      the Shoulder Activity Scale (SAS) into the Persian and determine its clinimetric
      properties including reliability, validity, and responsiveness in patients with
      shoulder disorders. METHOD: Persian version of the SAS was obtained after
      standard forward-backward translation. Three questionnaires were completed by the
      respondents: SAS, shoulder pain and disability index (SPADI), and Short-Form 36
      Health Survey (SF-36). The patients completed the SAS, 1 week after the first
      visit to evaluate the test-retest reliability. Construct validity was evaluated
      by examining the associations between the scores on the SAS and the scores
      obtained from the SPADI, SF-36, and age of the patients. To assess
      responsiveness, data were collected in the first visit and then again after 4
      weeks physiotherapy intervention. Test-retest reliability and internal
      consistency were assessed using Intra-class Correlation Coefficient (ICC) and
      Cronbach's alpha, respectively. To evaluate construct validity, Spearman's rank
      correlation was used. The ability of the SAS to detect changes was evaluated by
      the receiver-operating characteristics method. RESULTS: No problem or language
      difficulties were reported during translation process. Test-retest reliability of
      the SAS was excellent with an ICC of 0.98. Also, the marginal Cronbach's alpha
      level of 0.64 was obtained. The correlation between the SAS and the SPADI was
      low, proving divergent validity, whereas the correlations between the SAS and the
      SF-36/age were moderate proving convergent validity. A marginally acceptable
      responsiveness was achieved for the Persian SAS. CONCLUSIONS: The study provides
      some evidences to support the test-retest reliability, internal consistency,
      construct validity, and responsiveness of the Persian version of the SAS in
      patients with shoulder disorders. Therefore, it seems that this instrument is a
      useful measure of shoulder activity level in research setting and clinical
      practice. IMPLICATIONS FOR REHABILITATION: The shoulder activity scale (SAS) is a
      reliable, valid, and responsive measure of shoulder activity level in Persian
      speaking patients with different shoulder disorders. The results on clinimetric
      properties of the Persian SAS are comparable with its original, English version.
      Persian version of the SAS can be used in "clinical" and "research" settings of
      patients with shoulder disorders.

PMID- 25382218
TI  - Optimized on-line enantioselective capillary electrophoretic method for kinetic
      and inhibition studies of drug metabolism mediated by cytochrome P450 enzymes.
AB  - Pharmacokinetic and pharmacodynamic properties of a chiral drug can significantly
      differ between application of the racemate and single enantiomers. During drug
      development, the characteristics of candidate compounds have to be assessed prior
      to clinical testing. Since biotransformation significantly influences drug
      actions in an organism, metabolism studies represent a crucial part of such
      tests. Hence, an optimized and economical capillary electrophoretic method for on
      line studies of the enantioselective drug metabolism mediated by cytochrome P450
      enzymes was developed. It comprises a diffusion-based procedure, which enables
      mixing of the enzyme with virtually any compound inside the nanoliter-scale
      capillary reactor and without the need of additional optimization of mixing
      conditions. For CYP3A4, ketamine as probe substrate and highly sulfated gamma
      cyclodextrin as chiral selector, improved separation conditions for ketamine and
      norketamine enantiomers compared to a previously published electrophoretically
      mediated microanalysis method were elucidated. The new approach was thoroughly
      validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied
      to the determination of its kinetic parameters and the inhibition characteristics
      in presence of ketoconazole and dexmedetomidine. The determined parameters were
      found to be comparable to literature data obtained with different techniques. The
      presented method constitutes a miniaturized and cost-effective tool, which should
      be suitable for the assessment of the stereoselective aspects of kinetic and
      inhibition studies of cytochrome P450-mediated metabolic steps within early
      stages of the development of a new drug. 

PMID- 25382219
TI  - Distribution and characterization of rhogocyte cell types in the mantle tissue of
      Haliotis laevigata.
AB  - Molluscan rhogocytes are known to be the only cells able to synthesize hemocyanin
      that is one of the largest respiratory proteins in nature. However, investigation
      of rhogocyte cells in vitro is limited due to difficulty in isolating and
      establishing marine cell culture. The aim of this study was to investigate the
      nature and distribution of rhogocyte cells of Haliotis laevigata in the mantle
      tissue with respect to the expression of the two known isoforms of hemocyanin.
      Rhogocyte cells were identified using immunofluorescence-fluorescence in situ
      hybridization (IF-FISH) that involved simultaneous staining of localized
      hemocyanin by a polyclonal antibody while the mRNA was hybridized with FISH
      probes. The distribution of rhogocyte cells was demonstrated using flow
      cytometry, followed by cell sorting with fluorescence-activated cell sorter
      (FACS) and confocal microscope imaging for further characterization. Our results
      suggested that the mantle tissue is dominated by two distinct populations of
      rhogocyte cells that synthesize hemocyanin type 1. Observation with confocal
      microscopy of both populations revealed hemocyanin localization in the periphery
      of the cell membrane. Cell population with higher antibody signal had irregular
      and elongated cell morphology with punctate mRNA probe signals. The second
      population with lower antibody signal had ovoid morphology and wide distribution
      of mRNA probe signals. We suggest that these populations represent two distinct
      phases of hemocyanin biosynthesis of a single isoform, which is closely related
      to Haliotis tuberculata type 1 hemocyanin (HtH1). The knowledge acquired in this
      study enhances the understanding of the biology of rhogocyte cells and
      biosynthesis of hemocyanin. 

PMID- 25382220
TI  - Developing a new screening tool for nutritional risk in neonatal intensive care.

PMID- 25382217
TI  - Mechanical regulation of mesenchymal stem cell differentiation.
AB  - Biophysical cues play a key role in directing the lineage commitment of
      mesenchymal stem cells or multipotent stromal cells (MSCs), but the
      mechanotransductive mechanisms at play are still not fully understood. This
      review article first describes the roles of both substrate mechanics (e.g.
      stiffness and topography) and extrinsic mechanical cues (e.g. fluid flow,
      compression, hydrostatic pressure, tension) on the differentiation of MSCs. A
      specific focus is placed on the role of such factors in regulating the
      osteogenic, chondrogenic, myogenic and adipogenic differentiation of MSCs. Next,
      the article focuses on the cellular components, specifically integrins, ion
      channels, focal adhesions and the cytoskeleton, hypothesized to be involved in
      MSC mechanotransduction. This review aims to illustrate the strides that have
      been made in elucidating how MSCs sense and respond to their mechanical
      environment, and also to identify areas where further research is needed. 

PMID- 25382221
TI  - The views of European clinicians on guidelines for long-term follow-up of
      childhood cancer survivors.
AB  - BACKGROUND: Evidence-based guidelines are needed to guide effective long-term
      follow-up (LTFU) of childhood cancer survivors (CCS) at risk of late adverse
      effects (LAEs). We aimed to ascertain the use of LTFU guidelines throughout
      Europe, and seek views on the need for pan-European LTFU guidelines. PROCEDURES:
      One expert clinician from each of 44 European countries was invited to
      participate in an online survey. Information was sought regarding the use and
      content of LTFU guidelines in the respondent's centre and country, and their
      views about developing pan-European LTFU guidelines. RESULTS: Thirty-one
      countries (70%) responded, including 24 of 26 full EU countries (92%). LTFU
      guidelines were implemented nationally in 17 countries (55%). All guidelines
      included recommendations about physical LAEs, specific risk groups and frequency
      of surveillance, and the majority about psychosocial LAEs (70%), and healthy
      lifestyle promotion (65%). A minority of guidelines described recommendations
      about transition to age-appropriate LTFU services (22%), where LTFU should be
      performed (22%) and by whom (30%). Most respondents (94%) agreed on the need for
      pan-European LTFU guidelines, specifically including recommendations about
      surveillance for specific physical LAEs (97%), action to be taken if a specific
      LAE is detected (90%), minimum requirements for LTFU (93%), transition and health
      promotion (both 87%). CONCLUSIONS: Guidelines are not universally used throughout
      Europe. However, there is strong support for developing pan-European LTFU
      guidelines for CCS. PanCareSurFup (www.pancare.eu) will collaborate with partners
      to develop such guidelines, including recommendations for hitherto relatively
      neglected topics, such as minimum LTFU requirements, transition and health
      promotion. Pediatr Blood Cancer 2015;62:322-328. (c) 2014 Wiley Periodicals, Inc.

PMID- 25382222
TI  - Holy basil (Ocimum sanctum Linn.) essential oil delivery to swine
      gastrointestinal tract using gelatin microcapsules coated with aluminum
      carboxymethyl cellulose and beeswax.
AB  - Holy basil essential oil (HBEO) can be applied as a feed additive; however, its
      benefits depend on the available amount in the gastrointestinal tract. In this
      study, the physicochemical properties, including the release properties of three
      different microcapsules, HBEO-loaded gelatin microcapsules (UC), UC coated with
      aluminum carboxymethyl cellulose (CC), and UC coated with aluminum carboxymethyl
      cellulose-beeswax composite (CB), were compared. The encapsulation efficiency,
      HBEO content, and 2,2-diphenyl-2-picrylhydrazyl radical scavenging activity for
      the microcapsules were 95.4 +/- 0.17%, 66.7-67.7%, and 94.3-96.5%, respectively.
      Scanning electron microscopy and confocal laser scanning microscopy (CLSM)
      revealed nonuniform HBEO distributions in honeycomb-like networks in the
      microcapsules. An X-ray diffraction analysis determined that UC and CC
      microcapsules were amorphous, but CB microcapsules were semicrystalline. UV-vis
      spectrophotometer and CLSM analyses results determined that HBEO was released
      from CC and CB microcapsules in greater amounts than from UC microcapsules in
      simulated intestinal fluid. Therefore, the HBEO amount reaching the intestine can
      be controlled using the optimal encapsulation system. 

PMID- 25382223
TI  - Development of effective skin cancer treatment and prevention in xeroderma
      pigmentosum.
AB  - Xeroderma pigmentosum (XP) is a rare, recessively transmitted genetic disease
      characterized by increasingly marked dyspigmentation and xerosis (dryness) of sun
      exposed tissues, especially skin. Skin cancers characteristically develop in sun
      exposed sites at very much earlier ages than in the general population; these are
      often multiple and hundreds or even thousands may develop. Eight complementation
      groups have been identified. Seven groups, XP-A...G, are associated with
      defective genes encoding proteins involved in the nucleotide excision DNA repair
      (NER) pathway that recognizes and excises mutagenic changes induced in DNA by
      sunlight; the eighth group, XP-V, is associated with defective translesion
      synthesis (TLS) bypassing such alterations. The dyspigmentation, xerosis and
      eventually carcinogenesis in XP patients appear to be due to their cells' failure
      to respond properly to these mutagenic DNA alterations, leading to mutations in
      skin cells. A subset of cases, especially those in some complementation groups,
      may develop neurological degeneration, which may be severe. However, in most XP
      patients, in the past the multiple skin cancers have led to death at an early age
      due to either metastases or sepsis. Using either topical 5-fluorouracil or
      imiquimod, we have developed a protocol that effectively prevents most skin
      cancer development in XP patients. 

PMID- 25382224
TI  - Aggregation-induced emission rotors: rational design and tunable stimuli
      response.
AB  - A novel molecular design strategy is provided to rationally tune the stimuli
      response of luminescent materials with aggregation-induced emission (AIE)
      characteristics. A series of new AIE-active molecules (AIE rotors) are prepared
      by covalently linking different numbers of tetraphenylethene moieties together.
      Upon gradually increasing the number of rotatable phenyl rings, the sensitivity
      of the response of the AIE rotors to viscosity and temperature is significantly
      enhanced. Although the molecular size is further enlarged, the performance is
      only slightly improved due to slightly increased effective rotors, but with
      largely increased rotational barriers. Such molecular engineering and
      experimental results offer more in-depth insight into the AIE mechanism, namely,
      restriction of intramolecular rotations. Notably, through this rational design,
      the AIE rotor with the largest molecular size turns out to be the most
      viscosensitive luminogen with a viscosity factor of up to 0.98. 

PMID- 25382226
TI  - Research Letter: Investigating psychotic traits in poets.

PMID- 25382225
TI  - A synchrotron-based hydroxyl radical footprinting analysis of amyloid fibrils and
      prefibrillar intermediates with residue-specific resolution.
AB  - Structural models of the fibrils formed by the 40-residue amyloid-beta (Abeta40)
      peptide in Alzheimer's disease typically consist of linear polypeptide segments,
      oriented approximately perpendicular to the long axis of the fibril, and joined
      together as parallel in-register beta-sheets to form filaments. However, various
      models differ in the number of filaments that run the length of a fibril, and in
      the topological arrangement of these filaments. In addition to questions about
      the structure of Abeta40 monomers in fibrils, there are important unanswered
      questions about their structure in prefibrillar intermediates, which are of
      interest because they may represent the most neurotoxic form of Abeta40. To
      assess different models of fibril structure and to gain insight into the
      structure of prefibrillar intermediates, the relative solvent accessibility of
      amino acid residue side chains in fibrillar and prefibrillar Abeta40 preparations
      was characterized in solution by hydroxyl radical footprinting and structural
      mass spectrometry. A key to the application of this technology was the
      development of hydroxyl radical reactivity measures for individual side chains of
      Abeta40. Combined with mass-per-length measurements performed by dark-field
      electron microscopy, the results of this study are consistent with the core
      filament structure represented by two- and three-filament solid state nuclear
      magnetic resonance-based models of the Abeta40 fibril (such as 2LMN , 2LMO , 2LMP
      , and 2LMQ ), with minor refinements, but they are inconsistent with the more
      recently proposed 2M4J model. The results also demonstrate that individual
      Abeta40 fibrils exhibit structural heterogeneity or polymorphism, where regions
      of two-filament structure alternate with regions of three-filament structure. The
      footprinting approach utilized in this study will be valuable for characterizing
      various fibrillar and nonfibrillar forms of the Abeta peptide. 

PMID- 25382227
TI  - Resistance to leakage of various thicknesses of apical plugs of Bioaggregate
      using liquid filtration model.
AB  - AIM: The aim of this study was to compare the resistance to leakage of different
      thicknesses of Bioaggregate (BA) and 4-mm-thick white mineral trioxide aggregate
      (WMTA) in an apexification model using liquid filtration. METHODS: 32 extracted
      mandibular premolar teeth were sectioned at the cemento-enamel junction and 3-4
      mm from the tooth apex to obtain 12-mm-long root segments. The apical and coronal
      thirds were prepared with size two through six Gates Glidden burs. The teeth were
      divided into four groups according to material and thickness, as follows: Group
      1: 2-mm BA; Group 2: 4-mm BA; Group 3: 12-mm (total length) BA; Group 4: 4-mm
      WMTA (control). The empty parts of the roots in Groups 1, 2, and 4 were filled
      with gutta-percha and root canal sealer, and leakage was measured using fluid
      filtration. The data were analyzed using the Kruskal-Wallis H-test. RESULTS: No
      statistical differences in microleakage were observed between Groups 1, 2, and 4
      (P > 0.05). Group 3 (roots filled completely with BA) showed significantly less
      leakage than the other groups tested (P < 0.01). CONCLUSIONS: The findings of
      this study showed that 12 mm of BA exhibited the best resistance to leakage. At
      the same time, 2-4 mm of BA showed similar results when compared to 4-mm MTA. In
      light of these results, this study suggests that BA may be a good candidate for
      further clinical studies when used as an apical barrier for apexification.

PMID- 25382228
TI  - Structural insight into the aggregation of L-prolyl dipeptides and its effect on
      organocatalytic performance.
AB  - NMR and organocatalytic studies of four dipeptides derived from L-proline are
      described. Results indicate that important conformational changes around the
      catalytic L-proline moiety are observed for free dipeptides upon changing the
      adjacent amino acid. Also, an aggregation process is detected as the
      concentration increases. The self-association of the dipeptides has been fitted
      to a cooperative binding model. All the compounds have been assayed as catalysts
      for the conjugated addition of cyclohexanone to trans-beta-nitrostyrene in
      toluene. In agreement with the structural studies, noticeable changes in the
      catalytic performance are detected upon changing the catalyst concentration, as
      the catalyst is activated by self-aggregation.

PMID- 25382229
TI  - Validity of the dynamic Wisconsin Card Sorting Test for assessing learning
      potential in brain injury rehabilitation.
AB  - The dynamic Wisconsin Card Sorting Test (dWCST) examines the effects of brief
      training on test performance where pre- to post-test change reflects learning
      potential. The objective was to examine the validity of the dWCST as a measure of
      learning potential in patients with acquired brain injury (ABI). A total of 104
      patients with ABI completed the dWCST at rehabilitation admission. Performance of
      a subgroup (n=63) was compared to patients (n=28) who completed a repeated
      administration of the conventional WCST (rWCST). Furthermore, dWCST performance
      was compared between patients with ABI (n=63) and healthy controls (n=30) matched
      on gender, age, and education. Three learning potential indices were used: post
      test score, gain score, and a group classification (decliners, poor learners,
      strong learners, high achievers). The median dWCST administration time was 30
      min. The dWCST showed no floor or ceiling effects and the post-test and gain
      score were significantly intercorrelated. The pre-test score showed no
      significant associations with other neuropsychological tests. The learning
      potential indices were significantly associated with language and/or memory. In
      contrast to the dWCST group, the rWCST group showed no significant pre- to post
      test improvement. There were significantly more poor learners in the rWCST group.
      Compared to controls, patients obtained similar gains, but significantly lower
      pre- and post-test scores for the dWCST. The ratio of poor learners between
      groups was not significantly different. The results support the validity of the
      dWCST for assessing learning potential in patients with ABI. Further research is
      needed to investigate the predictive validity of the dWCST.

PMID- 25382230
TI  - RNA-Seq bulked segregant analysis enables the identification of high-resolution
      genetic markers for breeding in hexaploid wheat.
AB  - The identification of genetic markers linked to genes of agronomic importance is
      a major aim of crop research and breeding programmes. Here, we identify markers
      for Yr15, a major disease resistance gene for wheat yellow rust, using a
      segregating F2 population. After phenotyping, we implemented RNA sequencing (RNA
      Seq) of bulked pools to identify single-nucleotide polymorphisms (SNP) associated
      with Yr15. Over 27 000 genes with SNPs were identified between the parents, and
      then classified based on the results from the sequenced bulks. We calculated the
      bulk frequency ratio (BFR) of SNPs between resistant and susceptible bulks,
      selecting those showing sixfold enrichment/depletion in the corresponding bulks
      (BFR > 6). Using additional filtering criteria, we reduced the number of genes
      with a putative SNP to 175. The 35 SNPs with the highest BFR values were
      converted into genome-specific KASP assays using an automated bioinformatics
      pipeline (PolyMarker) which circumvents the limitations associated with the
      polyploid wheat genome. Twenty-eight assays were polymorphic of which 22 (63%)
      mapped in the same linkage group as Yr15. Using these markers, we mapped Yr15 to
      a 0.77-cM interval. The three most closely linked SNPs were tested across
      varieties and breeding lines representing UK elite germplasm. Two flanking
      markers were diagnostic in over 99% of lines tested, thus providing a reliable
      haplotype for marker-assisted selection in these breeding programmes. Our results
      demonstrate that the proposed methodology can be applied in polyploid F2
      populations to generate high-resolution genetic maps across target intervals. 

PMID- 25382231
TI  - Helicobacter pylori Infection in Children. Antimicrobial Resistance and Treatment
      Response.
AB  - BACKGROUND: The aim of this study was to determine the appropriateness of the
      recent recommendations for managing Helicobacter pylori infection in children in
      a university hospital in Southern Europe. Antimicrobial resistance and response
      to eradication therapy were also determined. MATERIALS AND METHODS: The presence
      of H. pylori was studied in 143 children: by gastric biopsy culture (GBC), (13)C
      urea breath test (UBT) and stool antigen immunochromatography test (SAIT) in 56
      children; by GBC and UBT in 20, by GBC and SAIT in 18, and by GBC alone in 49.
      Antimicrobial susceptibility was determined by E-test. Infection was defined as a
      positive culture or positivity in both UBT and SAIT. Disease progression was
      studied in 118 patients. First evaluation of symptoms was carried out at 3-6
      months after diagnosis and/or after treatment of the infection. RESULTS: H.
      pylori was detected in 74 from the 143 children analyzed (100% GBC positive,
      98.1% UBT positive, and 58.1% SAIT positive). The main symptom was chronic
      abdominal pain (n = 121). Macroscopic antral nodularity was observed in 29.7% of
      infected patients and in 5.8% of uninfected patients, respectively. Resistance to
      clarithromycin and metronidazole was found in 34.7 and 16.7%, respectively.
      Eradication when susceptible antimicrobials were used occurred in 78.7% (48/61)
      versus 37.5% (3/8) when the treatment included a drug with resistance (p = .024).
      In patients with recurrent abdominal pain, symptoms resolved in 92.9% (39/42)
      patients with HP eradication versus 42.9% (6/14) without HP eradication (p <
      .001). CONCLUSION: Treated patients often failed to meet the criteria established
      in the guidelines for H. pylori diagnostic screening and treatment because most
      of them had only recurrent abdominal pain, but remission of their symptoms was
      associated with H. pylori eradication.

PMID- 25382232
TI  - Efficacy of acotiamide in combination with esomeprazole for functional dyspepsia
      refractory to proton-pump inhibitor monotherapy.
AB  - Functional dyspepsia (FD) is a gastroduodenal disorder that presents as
      postprandial fullness, early satiation, or epigastric burning despite no evidence
      of a structural disease. Proton pump inhibitors (PPIs) are often the first choice
      for treating FD. However, some patients need additional medication because of
      residual symptoms despite a certain level of benefit from the PPI. For these
      patients, a combination of PPI and other agents has a possibly more beneficial
      effect than changing their medication. This study aimed to evaluate the efficacy
      of an initial PPI followed by combination therapy with PPI and acotiamide in FD
      patients with residual symptoms after an initial PPI. We enrolled 105 patients
      who started an initial PPI (20 mg of esomeprazole once a day). Twenty-three
      patients with residual symptoms received 100 mg of acotiamide, a cholinesterase
      inhibitor, three times a day with esomeprazole as a combination therapy for 2
      weeks. The symptoms were evaluated using the modified Frequency Scale for the
      Symptoms of Gastroesophageal Reflux Disease (mFSSG). Eighteen of 23 patients
      (78%) achieved an overall improvement in symptoms. Almost all FD-related symptoms
      statistically improved after the combination therapy, with an improvement in the
      mFSSG score relevant to the postprandial distress syndrome and epigastric pain
      syndrome. The symptoms improved regardless of age, sex, and the pre-combination
      therapy score of the mFSSG. Our findings suggest that the combination therapy of
      acotiamide and PPI may be effective in selected FD patients with insufficient
      improvement with an initial PPI. However, well-designed trials are required to
      confirm the efficacy. 

PMID- 25382233
TI  - ATF4: the perpetrator in axonal-mediated neurodegeneration in Alzheimer's
      disease.

PMID- 25382234
TI  - Impact of locomotion training with a neurologic controlled hybrid assistive limb
      (HAL) exoskeleton on neuropathic pain and health related quality of life (HRQoL)
      in chronic SCI: a case study (.).
AB  - Chronic neuropathic pain (CNP) is a common condition associated with spinal cord
      injury (SCI) and has been reported to be severe, disabling and often treatment
      resistant and therefore remains a clinical challenge for the attending
      physicians. The treatment usually includes pharmacological and/or
      nonpharmacological approaches. Body weight supported treadmill training (BWSTT)
      and locomotion training with driven gait orthosis (DGO) have evolved over the
      last decades and are now considered to be an established part in the
      rehabilitation of SCI patients. Conventional locomotion training goes along with
      improvements of the patients' walking abilities in particular speed and gait
      pattern. The neurologic controlled hybrid assistive limb (HAL(r), Cyberdyne Inc.,
      Ibraki, Japan) exoskeleton, however, is a new tailored approach to support motor
      functions synchronously to the patient's voluntary drive. This report presents
      two cases of severe chronic and therapy resistant neuropathic pain due to chronic
      SCI and demonstrates the beneficial effects of neurologic controlled exoskeletal
      intervention on pain severity and health-related quality of life (HRQoL). Both of
      these patients were engaged in a 12 weeks period of daily HAL(r)-supported
      locomotion training. In addition to improvements in motor functions and walking
      abilities, both show significant reduction in pain severity and improvements in
      all HRQoL domains. Although various causal factors likely contribute to abatement
      of CNP, the reported results occurred due to a new approach in the rehabilitation
      of chronic spinal cord injury patients. These findings suggest not only the
      feasibility of this new approach but in conclusion, demonstrate the effectiveness
      of neurologic controlled locomotion training in the long-term management of
      refractory neuropathic pain. Implications for Rehabilitation CNP remains a
      challenge in the rehabilitation of chronic SCI patients. Locomotion training with
      the HAL exoskeleton seems to improve CNP in chronic SCI. HAL locomotion training
      is feasible and safe in the rehabilitation of chronic SCI patients.

PMID- 25382235
TI  - Extension of the Peters-Belson method to estimate health disparities among
      multiple groups using logistic regression with survey data.
AB  - Determining the extent of a disparity, if any, between groups of people, for
      example, race or gender, is of interest in many fields, including public health
      for medical treatment and prevention of disease. An observed difference in the
      mean outcome between an advantaged group (AG) and disadvantaged group (DG) can be
      due to differences in the distribution of relevant covariates. The Peters-Belson
      (PB) method fits a regression model with covariates to the AG to predict, for
      each DG member, their outcome measure as if they had been from the AG. The
      difference between the mean predicted and the mean observed outcomes of DG
      members is the (unexplained) disparity of interest. We focus on applying the PB
      method to estimate the disparity based on binary/multinomial/proportional odds
      logistic regression models using data collected from complex surveys with more
      than one DG. Estimators of the unexplained disparity, an analytic variance
      covariance estimator that is based on the Taylor linearization variance
      covariance estimation method, as well as a Wald test for testing a joint null
      hypothesis of zero for unexplained disparities between two or more minority
      groups and a majority group, are provided. Simulation studies with data selected
      from simple random sampling and cluster sampling, as well as the analyses of
      disparity in body mass index in the National Health and Nutrition Examination
      Survey 1999-2004, are conducted.  Empirical results indicate that the Taylor
      linearization variance-covariance estimation is accurate and that the proposed
      Wald test maintains the nominal level.

PMID- 25382237
TI  - Diagnosis and management of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease
      characterized histologically by destruction of intrahepatic bile ducts and
      serologically by the presence of antimitochondrial antibodies. The incidence and
      prevalence of PBC are increasing. Fatigue and pruritus are common symptoms in
      PBC, although the proportion of asymptomatic PBC is increasing due to the
      widespread use of screening biochemical tests and antimitochondrial antibody
      assays. PBC may eventually lead to cirrhosis and its consequent complications. In
      the 1980s, PBC was the leading indication for liver transplantation.
      Ursodeoxycholic acid is the only US FDA-approved therapeutic agent for PBC.
      Clinical trials have shown that the use of ursodeoxycholic acid in PBC results in
      reduction of liver biochemistries, a delay in histological progression, a delay
      in the development of varices and improvement in survival without liver
      transplantation. 

PMID- 25382238
TI  - Integrative review: an evaluation of the methods used to explore the relationship
      between overtime and patient outcomes.
AB  - AIMS: To analyse, critically, methods employed to explore the relationship
      between nursing overtime and patient outcomes to strengthen future research.
      BACKGROUND: Nursing overtime hours have been increasing in the Western world
      since the 1980's; however, research detailing its implications for patient
      outcomes has not kept pace. Studies exploring the relationship between nursing
      overtime and patient outcomes have produced conflicting results and are deficient
      in number and rigour. DESIGN: Whittemore and Knafl's revised framework for
      integrative reviews guided the analysis. DATA SOURCES: A comprehensive multi-step
      search (1980-2012) of literature related to nursing overtime and patient outcomes
      in the CINAHL, Medline, PubMED, EMBASE and PsychInfo databases was performed.
      Reference lists and Google searches were completed for additional sources. Nine
      research papers met the inclusion criteria. REVIEW METHODS: All nine articles
      were included in the review. A systematic, iterative approach was used to extract
      and reduce the data to draw conclusions. RESULTS: There appears to be a positive
      relationship between nursing overtime and patient outcomes, however, eight of the
      nine studies revealed limitations in: (1) the definition and measurement of
      overtime; (2) data aggregation (organizationally and temporally) and (3)
      recognition or control of potential confounding variables. CONCLUSION: The
      quality in this research sample limits the ability of this body of work to be the
      basis of staffing policies. Future researchers need to be explicit in detailing
      their methods alongside a renewed commitment from administration to develop a
      tracking system of important parameters at the individual and bedside level.

PMID- 25382239
TI  - Treatment of the chronic total occlusion: a call to action for the interventional
      community.
AB  - There is substantial evidence that recanalization of a chronic total occlusion is
      beneficial; nonetheless, it is generally underutilized in clinical practice. We
      consider the Aesop's fable of the "Fox and the Grapes" as analogous to the
      current situation in interventional cardiology. The technical challenges in
      achieving CTO recanalization has led interventionalists, clinical cardiologists,
      and sometimes even patients to believe that CTO recanalization is not effective,
      and, therefore, not needed. This perspective reviews available data regarding
      efficacy and safety of CTO percutaneous coronary intervention (PCI) in the
      current drug-eluting stent era, discusses areas where more studies are required,
      and encourages the interventional community to utilize CTO PCI where appropriate
      based on current evidence.

PMID- 25382240
TI  - Anatomy of the nerves and ganglia of the aortic plexus in males.
AB  - It is well accepted that the aortic plexus is a network of pre- and post
      ganglionic nerves overlying the abdominal aorta, which is primarily involved with
      the sympathetic innervation to the mesenteric, pelvic and urogenital organs.
      Because a comprehensive anatomical description of the aortic plexus and its
      connections with adjacent plexuses are lacking, these delicate structures are
      prone to unintended damage during abdominal surgeries. Through dissection of
      fresh, frozen human cadavers (n = 7), the present study aimed to provide the
      first complete mapping of the nerves and ganglia of the aortic plexus in males.
      Using standard histochemical procedures, ganglia of the aortic plexus were
      verified through microscopic analysis using haematoxylin & eosin (H&E) and anti
      tyrosine hydroxylase stains. All specimens exhibited four distinct sympathetic
      ganglia within the aortic plexus: the right and left spermatic ganglia, the
      inferior mesenteric ganglion and one previously unidentified ganglion, which has
      been named the prehypogastric ganglion by the authors. The spermatic ganglia were
      consistently supplied by the L1 lumbar splanchnic nerves and the inferior
      mesenteric ganglion and the newly characterized prehypogastric ganglion were
      supplied by the left and right L2 lumbar splanchnic nerves, respectively.
      Additionally, our examination revealed the aortic plexus does have potential for
      variation, primarily in the possibility of exhibiting accessory splanchnic
      nerves. Clinically, our results could have significant implications for
      preserving fertility in men as well as sympathetic function to the hindgut and
      pelvis during retroperitoneal surgeries. 

PMID- 25382246
TI  - Atomically-thin two-dimensional sheets for understanding active sites in
      catalysis.
AB  - Catalysis can speed up chemical reactions and it usually occurs on the low
      coordinated steps, edges, terraces, kinks and corner atoms that are often called
      "active sites". However, the atomic level interplay between active sites and
      catalytic activity is still an open question, owing to the large difference
      between idealized models and real catalysts. This stimulates us to pursue a
      suitable material model for studying the active sites-catalytic activity
      relationship, in which the atomically-thin two-dimensional sheets could serve as
      an ideal model, owing to their relatively simple type of active site and the
      ultrahigh fraction of active sites that are comparable to the overall atoms. In
      this tutorial review, we focus on the recent progress in disclosing the factors
      that affect the activity of reactive sites, including characterization of atomic
      coordination number, structural defects and disorder in ultrathin two-dimensional
      sheets by X-ray absorption fine structure spectroscopy, positron annihilation
      spectroscopy, electron spin resonance and high resolution transmission electron
      microscopy. Also, we overview their applications in CO catalytic oxidation,
      photocatalytic water splitting, electrocatalytic oxygen and hydrogen evolution
      reactions, and hence highlight the atomic level interplay among coordination
      number, structural defects/disorder, active sites and catalytic activity in the
      two-dimensional sheets with atomic thickness. Finally, we also present the major
      challenges and opportunities regarding the role of active sites in catalysis. We
      believe that this review provides critical insights for understanding the
      catalysis and hence helps to develop new catalysts with high catalytic activity. 

PMID- 25382245
TI  - Identification of known and novel germ cell cancer-specific (embryonic) miRs in
      serum by high-throughput profiling.
AB  - microRNAs (miRs) are short non-coding RNA molecules (~21 nucleotides) involved in
      regulation of translation. As such they are crucial for normal cell development
      and differentiation as well as cellular maintenance. Dysregulation of miRs has
      been reported in various diseases, including cancer. Interestingly, miRs can be
      informative as tumor classifiers and disease biomarkers. Recent studies
      demonstrated the presence of miRs in body fluids like serum, thus providing a
      putative non-invasive tool to study and monitor disease state. Earlier targeted
      studies by several independent groups identified specific embryonic miRs as
      characteristic for germ cell tumors (GCT) (miR-371-2-3 & miR-302/367 clusters).
      This study reports a high-throughput miR profiling (~750 miRs) approach on serum
      from testicular germ cell tumor patients (14 seminoma and 10 non-seminoma) and
      controls (n = 11), aiming at independent identification of miRs as candidate
      biomarkers for testicular GCT. A magnetic bead capture system was used to isolate
      miRs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for
      profiling. The previously identified miRs 371 and 372 were confirmed to be
      specifically elevated in serum from germ cell tumor patients. In addition,
      several novels miRs were identified that were discriminative between germ cell
      cancer and controls: miR-511, -26b, -769, -23a, -106b, -365, -598, -340, and let
      7a. In conclusion, this study validates the power of the embryonic miRs 371 and
      372 in detecting malignant GCT (SE and NS) based on serum miR levels and
      identifies several potential novel miR targets. 

PMID- 25382247
TI  - Prognostic factor from MR spectroscopy in rat with astrocytic tumour during
      radiation therapy.
AB  - OBJECTIVE: To investigate the relationship between the tumour volume and
      metabolic rates of astrocytic tumours using MR spectroscopy (MRS) during
      radiation therapy (RT). METHODS: 12 healthy male Sprague-Dawley(r) rats (Sprague
      Dawley Animal Company, Madison, WI) were used, and a tumour model was created
      through injecting C6 tumour cells into the right caudate nuclei of the rats.
      Tumours grew for 18 days after the injection and before the imaging study and
      radiation treatment. MRS was performed with two-dimensional multivoxel point
      resolved spectroscopy sequence using a GE Signa VH/i 3.0-T MR scanner (GE
      Healthcare, Milwaukee, WI) equipped with rat-special coil. RT was given on the
      19th day with a dose of 4 Gy in one single fraction. The image examinations were
      performed before RT, and on the 4th, 10th, 14th and 20th days after treatment,
      respectively. GE FuncTool software package (GE Healthcare) was used for post
      processing of spectrum. RESULTS: Metabolic ratios of serial MRS decrease
      progressively with time after RT. Choline-containing components (Cho)/creatine
      and creatine phosphate (Cr) ratios immediately prior to RT differed significantly
      from those on the 10th, 14th and 20th days after RT; both Cho/N-acetyl aspartate
      (NAA) ratios and NAA/Cr ratios immediately prior to RT differed significantly
      from those on the 14th and 20th days after RT. A positive correlation between
      changes of tumour volume and changes of Cho/Cr, lipid and lactate/Cr and
      glutamate plus glutamine/Cr ratio was observed on the 4th day after RT.
      CONCLUSION: MRS provides potential in monitoring tumour response during RT, and
      the imaging biomarkers predict the response of astrocytic tumours to treatment.
      ADVANCES IN KNOWLEDGE: MRS is combined with both tumour size and Ki-67 labelling
      index to access tumour response to radiation.

PMID- 25382248
TI  - A Framework for Categorization of the Economic Impacts of Outbreaks of Highly
      Contagious Livestock Diseases.
AB  - A framework for categorization of economic impacts of outbreaks of highly
      contagious livestock diseases (HCLD) is presented. This framework interprets
      veterinary measures to control HCLD outbreaks with reference to economic
      definitions of costs and benefits, and the implications for value losses both for
      different stakeholders affected and society as a whole. Four cost categories are
      identified, that is virus control-related direct costs (DC), spread prevention
      and zoning-related direct consequential costs (DCC), market and price disruption
      related costs during (indirect consequential costs, ICC) and after the outbreak
      (aftermath costs, AC). The framework is used to review existing literature on
      cost estimation for different stakeholders. This review shows considerable
      differences between studies, making comparison of results difficult and
      susceptible to misunderstanding. It is concluded that the framework provides a
      logical basis for all future analyses of the economic impacts of HCLD. 

PMID- 25382249
TI  - Assessment of health-related quality of life of patients after kidney
      transplantation in comparison with hemodialysis and peritoneal dialysis.
AB  - BACKGROUND: The quality of life may determine the efficacy of renal replacement
      therapy (RRT). The purpose of the study was to compare the health-related quality
      of life (HRQOL) of end-stage renal disease (ESRD) patients depending on RRT
      method. MATERIAL/METHODS: The studies were conducted on 120 patients divided into
      3 groups depending on RRT method: 30 peritoneal dialysis (PD) patients, 40
      hemodialysis (HD) patients, and 47 post-kidney transplantation (KTx) patients.
      The following research tools were used: (1) Medical Outcomes Study 36 - the Short
      Form (SF-36 v.1); (2) Kidney Disease Quality of Life Short Form (KDQOL-SFTM
      v.1.3); and (3) disease history. The relevance level was p<0.05. RESULTS: The
      evaluation of PCS by HD and PD patients is poorer compared to patients in the 3rd
      and 12th month after KTx (34.7 +/- 7.4 vs. 37.51 +/- 10.63 vs. 45.01 +/- 9.43 vs.
      45.55 +/- 8.62; p<0.05; respectively). PCS statistically significantly correlated
      with the following: SBP (r=-0.54; p<0.05), DBP (r=-0.58; p<0.05), and creatinine
      concentration (r=0.46; p<0.05) in the 12(th) month after KTx. CONCLUSIONS: HRQOL
      of ESRD patients differed depending on the RRT method: top values were shown by
      post-KTx patients, lower by PD patients, and the bottom ones by HD patients.
      Along with patient age, increased BP, and BMI, a drop in value of HRQOL in post
      Tx or PD patients was observed. When choosing RTT method, patients may use the
      results of the evaluation of quality of life. A preferred lifestyle, and
      predominantly the work status and quality of social interaction, should decide
      the choice of treatment.

PMID- 25382250
TI  - Spontaneous exfoliation and tailoring of MoS2 in mixed solvents.
AB  - Spontaneous exfoliation of MoS2 is achieved in H2O2-NMP mixed solvents with a
      yield of over 60 wt%, operated under mild conditions. H2O2-prompted sheet
      tailoring effect induces a size evolution of MoS2 nanosheets from micro-scale to
      nano-scale. Furthermore, the concurrent dissolution also affords an approach to
      introduce structural defects in the nanosheets. 

PMID- 25382251
TI  - Outcomes after combined liver-kidney transplant vs. kidney transplant followed by
      liver transplant.
AB  - INTRODUCTION: The decision for isolated kidney transplant (KT) vs. combined liver
      kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with
      compensated cirrhosis remains controversial. We sought to determine outcomes of
      patients requiring listing for a liver transplant (LT) following either a
      cadaveric or living donor KT and compare these outcomes to similar patients
      receiving a CLKT. METHODS: Our dataset included the United Network for Organ
      Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) kidney files
      from 1987 to 2012 after being joined with the liver files from 2002 to 2012.
      Outcomes of patients who received a CLKT with an international normalized ratio
      (INR) <=1 and total bilirubin <=1 were compared to patients who received a
      primary KT and subsequently required listing for LT between zero and five yr or
      after five yr. RESULTS: For the three groups, 244 patients had a CLKT, 216 were
      wait-listed for LT between zero and five yr after KT (0-5 WL), and 320 were wait
      listed five yr after KT (+5 WL). From the time of KT, the 0-5 WL group had
      significantly worse survival than the CLKT group and the +5 WL group. The +5 WL
      had the best survival of all groups. For the 0-5 WL group, 45% underwent LT and
      40% died while waiting compared to the +5 WL group with 53% having LT and 26%
      died while waiting. At the time of LT, the 0-5 WL group had a higher model for
      end-stage liver disease (MELD) score, higher incidence of being in the ICU at the
      time of transplant, and higher incidence of requiring life support. From the time
      of LT, the CLKT trended toward better survival (p = 0.0549) than both the 0-5 WL
      and +5 WL groups, which had equivalent survival. CONCLUSION: The 0-5 WL group is
      a higher risk group with poorer survival due to a higher incidence of dying on
      the waitlist. Better identification of patients with a high risk for hepatic
      decompensation following KT and agreement for regional exception for LT in the
      event of decompensation may improve utilization of organs and better survival for
      those patients.

PMID- 25382252
TI  - Giant morphological change in layered microribbons featuring reversible sliding
      of stacking layers.
AB  - A light-induced giant lateral or longitudinal morphological change in layered
      microribbons is reported. This morphological change originates from the
      directional sliding of the stacking layers with respect to one another between
      their polar surfaces, into which the photoexcited intermolecular non-bonded
      distortion is translated. Upon exposure to an electron beam, the laterally
      displaced layers slide back to their original positions. 

PMID- 25382254
TI  - Does limiting glutamatergic transmission in subthalamic nucleus mimic deep brain
      stimulation?

PMID- 25382253
TI  - Identification and characterization of a small-molecule inhibitor of death
      associated protein kinase 1.

PMID- 25382258
TI  - Selective and scalable synthesis of trifluoromethanesulfenamides and fluorinated
      unsymmetrical disulfides using a shelf-stable electrophilic SCF3 reagent.
AB  - The chemoselective trifluoromethylthiolation of nitrogen nucleophiles and thiols
      using N-(trifluoromethylthio)phthalimide under mild, metal-free conditions is
      described. A series of trifluoromethanesulfenamides and unsymmetrical disulfides
      is prepared from the corresponding aliphatic and aromatic amines and thiols in
      good yields. The reactions are operationally simple and tolerate a wide variety
      of functional groups. Trifluoromethanesulfenamides and disulfides belong to
      interesting classes of organic molecules which possess remarkable properties for
      medicinal and agrochemical applications. 

PMID- 25382257
TI  - Risk factors for abandonment of Wilms tumor therapy in Kenya.
AB  - BACKGROUND: Survival from Wilms tumor (WT) in sub-Saharan Africa remains dismal
      as a result of on-therapy mortality and treatment abandonment. Review of patients
      diagnosed from 2008 to 2011 in our Kenyan Wilms Tumor Registry showed a loss to
      follow up (LTFU) rate approaching 50%. The purpose of this study was to trace
      those LTFU, estimate the survival rate, and identify risk factors for treatment
      abandonment. PROCEDURE: We administered a comprehensive survey to parents of
      patients with WT at the two largest referral hospitals in Kenya to identify
      barriers to care. We also telephoned families who had abandoned care to determine
      vital status and identify risk factors for treatment abandonment. RESULTS: Of 136
      registered patients, 77 were confirmed dead (56.7%), 38 remained alive (27.9%),
      and the vital status of 21 patients remains unknown (15.4%). After contacting 33
      of the patients who either abandoned curative treatment (n = 34) or did not
      attend off-therapy visits (n = 20), the best estimate of 2-year overall survival
      of patients with WT in Kenya approaches 36%. Sixty-three percent of parents
      misunderstood treatment plans and 55% encountered financial barriers. When asked
      how to increase comfort with the child's treatment, 27% of parents volunteered
      improving inefficient services and 26% volunteered reducing drug-unavailability.
      CONCLUSIONS: Treatment abandonment remains a significant problem contributing to
      increased mortality from WT in developing countries. This multi-center survey
      identified the barriers to treatment completion from the parental perspective to
      be lack of education about WT and treatment, financial constraints, need for
      quality improvement, and drug-unavailability. Pediatr Blood Cancer 2015;62:252
      256. (c) 2014 Wiley Periodicals, Inc.

PMID- 25382259
TI  - Site-selective hexa-hetero-functionalization of alpha-cyclodextrin an
      archetypical C6-symmetric concave cycle.
AB  - Access to Cn (n>4) symmetric cyclic concave molecules with a different function
      on each of their n subunits is an unmet challenge. The reason lies in the lack of
      a post-functionalization method whose site selectivity is sufficiently
      understood, predictable and modulable to access most functionalization patterns.
      Here we disclose a new site-directing rule for a debenzylation reaction on
      cyclodextrins that solves this problem and allows the unprecedented access to
      penta- and ultimately hexa-differentiations of such C6 concave cycles. This
      achievement opens the access to objects with very high-density information. 

PMID- 25382260
TI  - Free energy simulations of active-site mutants of dihydrofolate reductase.
AB  - This study employs hybrid quantum mechanics-molecular mechanics (QM/MM)
      simulations to investigate the effect of mutations of the active-site residue I14
      of E. coli dihydrofolate reductase (DHFR) on the hydride transfer. Recent kinetic
      measurements of the I14X mutants (X = V, A, and G) indicated slower hydride
      transfer rates and increasingly temperature-dependent kinetic isotope effects
      (KIEs) with systematic reduction of the I14 side chain. The QM/MM simulations
      show that when the original isoleucine residue is substituted in silico by
      valine, alanine, or glycine (I14V, I14A, and I14G DHFR, respectively), the free
      energy barrier height of the hydride transfer reaction increases relative to the
      wild-type enzyme. These trends are in line with the single-turnover rate
      measurements reported for these systems. In addition, extended dynamics
      simulations of the reactive Michaelis complex reveal enhanced flexibility in the
      mutants, and in particular for the I14G mutant, including considerable
      fluctuations of the donor-acceptor distance (DAD) and the active-site hydrogen
      bonding network compared with those detected in the native enzyme. These
      observations suggest that the perturbations induced by the mutations partly
      impair the active-site environment in the reactant state. On the other hand, the
      average DADs at the transition state of all DHFR variants are similar. Crystal
      structures of I14 mutants (V, A, and G) confirmed the trend of increased
      flexibility of the M20 and other loops. 

PMID- 25382261
TI  - Molecular biology and biophysical properties of ion channel gating pores.
AB  - The voltage sensitive domain (VSD) is a pivotal structure of voltage-gated ion
      channels (VGICs) and plays an essential role in the generation of electrochemical
      signals by neurons, striated muscle cells, and endocrine cells. The VSD is not
      unique to VGICs. Recent studies have shown that a VSD regulates a phosphatase.
      Similarly, Hv1, a voltage-sensitive protein that lacks an apparent pore domain,
      is a self-contained voltage sensor that operates as an H+ channel. VSDs are
      formed by four transmembrane helices (S1-S4). The S4 helix is positively charged
      due to the presence of arginine and lysine residues. It is surrounded by two
      water crevices that extend into the membrane from both the extracellular and
      intracellular milieus. A hydrophobic septum disrupts communication between these
      water crevices thus preventing the permeation of ions. The septum is maintained
      by interactions between the charged residues of the S4 segment and the gating
      charge transfer center. Mutating the charged residue of the S4 segment allows the
      water crevices to communicate and generate gating pore or omega pore. Gating pore
      currents have been reported to underlie several neuronal and striated muscle
      channelopathies. Depending on which charged residue on the S4 segment is mutated,
      gating pores are permeant either at depolarized or hyperpolarized voltages.
      Gating pores are cation selective and seem to converge toward Eisenmann's first
      or second selectivity sequences. Most gating pores are blocked by guanidine
      derivatives as well as trivalent and quadrivalent cations. Gating pores can be
      used to study the movement of the voltage sensor and could serve as targets for
      novel small therapeutic molecules.

PMID- 25382262
TI  - Reliability of Repeated Measurements on Post-Burn Scars with Corneometer CM
      825((r)).
AB  - BACKGROUND/PURPOSE: The water content in burn scars, the parameter of stratum
      corneum water holding capacity, is an important feature in evaluation of
      biophysical properties of scars. Nevertheless, quantifiying this parameter is a
      challenge. In this study, the reliability of repeated water content measurements
      with Corneometer CM825((r)) on (burn) scars was investigated. METHODS: Intra
      observer reliability, inter-observer reliability and day-by-day variability were
      examined on 30 scars by means of intra-class correlation coefficient (ICC) and
      within-subject coefficient of variation (WSCV). Bland-Altman plots with '95%
      limits of agreement' were constructed. RESULTS: Results revealed excellent ICC
      values (ICCintra  = 0.985; ICCinter  = 0.984) with relatively low WSCV (WSCVintra
      = 6.3%; WSCVinter  = 10.6%) for respectively intra- and inter-observer
      reliability. However, the Bland-Altman plot showed that more than 5% of
      differences were expected to exceed 4 a.u., the limit of what has been defined as
      a clinically acceptable difference. Results for day-by-day variability showed
      good ICC value (ICCday-by-day  = 0.849) and higher WSCV (WSCVday-by-day  =
      20.5%). CONCLUSION: The Corneometer CM825((r)) is an objective and sensitive
      instrument for water content measurements. On the basis of our results, we
      concluded that the instrument can be used in clinical trials, but only under very
      strict conditions with standardized test protocol, preferably in combination with
      the evaluation of other physiological parameters.

PMID- 25382263
TI  - Establishing the content validity of the Sexual Arousal, Interest, and Drive
      Scale and the Hypogonadism Energy Diary.
AB  - AIM: The aim of this qualitative analysis was to establish the content validity
      of two new patient-reported outcome (PRO) measures: Sexual Arousal, Interest, and
      Drive Scale (SAID) and Hypogonadism Energy Diary (HED). METHODS: Four separate
      qualitative studies were conducted with 125 men with hypogonadism (mean age: 53
      years, 85% adult onset). Study 1 used focus groups/interviews to identify
      important and relevant concepts related to the experience of hypogonadism and its
      treatment in men primarily with adult-onset hypogonadism. Study 2 tested items
      generated for assessments of low sex drive and low energy. Study 3 used
      interviews to confirm in men with early-onset hypogonadism that low sex drive and
      low energy were also important and relevant symptoms. Study 4 tested final
      versions of the two PROs and determined equivalency of paper-based and electronic
      versions of the two PROs. RESULTS: Of the concepts emerging in Studies 1 and 3,
      low sex drive and low energy were the symptoms most often spontaneously
      mentioned. Coding of transcripts from Studies 1 and 3 led to the generation of
      items for the SAID and HED. After item testing (Studies 2 and 4), the final SAID
      included five items pertaining to arousal, interest in sex and sex drive with a 7
      day recall period and the final HED included two items (energy, tired/exhausted)
      to be administered three times per day. CONCLUSION: The SAID and HED have content
      validity established according to regulatory guidance and, therefore, the
      potential to provide the patient perspective of treatments for hypogonadism.

PMID- 25382264
TI  - Immediate disappearance of hemifacial spasm after partial removal of ponto
      medullary junction anaplastic astrocytoma: case report.
AB  - Hemifacial spasm (HFS) is generally caused by a neurovascular conflict (NC) at
      the root exit zone (REZ) of the facial nerve at the brainstem. Although a direct
      compression to the seventh cranial nerve (CN) by the anterior inferior cerebellar
      artery (AICA) is generally the most frequent cause, secondary HFS may be related
      to other pathological conditions. HFS due to an intracranial mass lesion is
      exceptionally rare and it has been reported in very few cases. The online
      database was searched for English-language articles reporting cases of HFS due to
      brainstem mass lesions and the possible pathophysiological mechanisms involved in
      its genesis. A 47-year-old man affected by an anaplastic astrocytoma of the
      brainstem at the level of the ponto-medullary junction developed right HFS. He
      underwent a subtotal surgical removal of the tumor with complete resolution of
      the HFS. This is the ninth reported case of HFS caused by an intrinsic brainstem
      tumor. The exceptional rarity of the relationship between intra-axial tumors and
      peripheral HFS was analyzed. 

PMID- 25382265
TI  - Endodontic performance by Flemish dentists: have they evolved?
AB  - AIM: To gather information on aspects of endodontic practice and referral
      behaviour by Flemish (Dutch-speaking Belgian) dentists and to compare the results
      with an earlier investigation. METHODOLOGY: A postal questionnaire was
      distributed to 4468 active Flemish dentists. It consisted of multiple-choice
      questions on endodontic practice and endodontic referral need. Basic information
      on age, gender, year of qualification and clinical specialty was also obtained.
      The questionnaire was free of charge to return. Data were imported in a database,
      subjected to descriptive and analytical statistics and compared to those of an
      earlier, comparable survey. RESULTS: The response rate was 18.5%. Of all
      respondents, 95% were general practitioners. More than half (56%) of the
      respondents never or seldom used rubber dam during endodontic treatment. The use
      of sodium hypochlorite as an irrigant was well established (80% of respondents
      using it), whereas the use of EDTA was limited. Female respondents were more
      likely to refer to an endodontist than male (70 versus 49%). Referrals for
      treatment of root canal obstruction (48%), perforations and root resorption (42%)
      and retreatment (39%) were rated 'very important'. Younger respondents more
      frequently made use of magnification, rotary instruments and rubber dam.
      Activation of irrigants was incorporated by a small number of respondents (50%
      never, 12.6% seldom). Cold lateral condensation was used by most GDPs (35.3%
      always, 19.5% frequently). CONCLUSIONS: Endodontic practice of general dentists
      in Flanders did not always comply with quality guidelines. However, when
      comparing the present data with those of a previous study, an obvious trend
      towards a more present-day treatment protocol is noticeable, as well as an
      increased appeal for endodontic referral.

PMID- 25382266
TI  - Autoimmune thyroid disease in Colombian patients with systemic lupus
      erythematosus.
AB  - OBJECTIVES: To determine the prevalence and the predictive factors of autoimmune
      hypothyroidism (AH) within a systemic lupus erythematosus (SLE) cohort and to
      analyse the current information concerning the prevalence and impact of
      autoimmune thyroid disease (AITD) and thyroid autoimmunity in patients with SLE.
      METHODS: A total of 376 patients with SLE were assessed for the presence of the
      following: (i) confirmed AH, (ii) positive thy-roperoxidase/thyroglobulin
      antibodies [TPOAb/TgAb] without hypothyroidism, (iii) nonautoimmune
      hypothyroidism and (iv) SLE patients with neither. Multivariate analysis and a
      classification and regression tree model were used to analyse data. The current
      information was discussed through a systematic literature review (SLR). RESULTS:
      In our cohort, the prevalence of confirmed AH was 12%. However, in euthyroid
      patients with SLE, TPOAb and TgAb were observed in 21% and 10%, respectively.
      Patients with confirmed AH were significantly older and had later age at onset of
      the disease. Smoking (adjusted odds ratio (AOR) 6.93, 95% CI 1.98-28.54, P =
      0.004), Sjogren's Syndrome (SS) (AOR 23.2, 95% CI 1.89-359.53, P = 0.015) and
      positivity for anticyclic citrullinated peptide (anti-CCP) (AOR 10.35, 95% CI
      1.04-121.26, P = 0.047) were associated with AH-SLE, regardless of gender and
      duration of the disease. Smoking and SS were confirmed as predictors of AH-SLE.
      In the SLR, the prevalence of AITD ranged from 1% to 60%. The factors associated
      with this polyautoimmunity were female gender, older age, smoking, certain
      autoantibodies, SS, and cutaneous and articular involvement. CONCLUSIONS: AITD is
      frequent in SLE and does not affect the severity of SLE. Identified risk factors
      will assist clinicians in the search for AITD. Our results encourage smoke-free
      policies in patients with SLE.

PMID- 25382267
TI  - The Role of Rac1 on Carbachol-induced Contractile Activity in Detrusor Smooth
      Muscle from Streptozotocin-induced Diabetic Rats.
AB  - This study was designed to determine the role of the small GTPase Rac1 on
      carbachol-induced contractile activity in detrusor smooth muscle using small
      inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also
      evaluated. In the streptozotocin (STZ)-induced diabetic rat model, three study
      groups were composed of control, diabetic and insulin-treated diabetic subjects.
      The detrusor muscle strips were suspended in organ baths at the end of 8-12 weeks
      after STZ injection. Carbachol (CCh) (10(-9) -10(-4) M) concentration-response
      curves were obtained both in the absence and in the presence of Rac1 inhibitor
      NSC 23766 (0.1, 1 and 10 MUM). Diabetes-related histopathological changes and
      Rac1 expressions were assessed by haematoxylin and eosin staining and
      immunohistochemical staining, respectively. CCh caused dose-dependent contractile
      responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh-induced
      contractile responses in all groups, but this inhibition seen in both diabetes
      groups was greater than in the control group. Histological examination revealed
      an increased bladder wall thickness both in the diabetes and in the insulin
      treated diabetes groups compared to the control group. In immunohistochemical
      staining, expression of Rac1 was observed to be increased in all layers of
      bladder in both diabetic groups compared to the control group. In the diabetic
      bladders, increased expression of Rac1 and considerable inhibition of CCh-induced
      responses in the presence of NSC 23766 compared to those of the control group may
      indicate a specific role of Rac1 in diabetes-related bladder dysfunction,
      especially associated with cholinergic mediated detrusor overactivity.

PMID- 25382268
TI  - Oxidative stress is decreased in physically active sickle cell SAD mice.
AB  - Oxidative stress plays a crucial role in sickle cell disease (SCD)
      physiopathology. Given that chronic physical activity is known to decrease
      reactive oxygen species (ROS) and increase nitric oxide (NO) bioavailability in
      healthy subjects and in patients with cardiovascular or inflammatory pathologies,
      modulating these factors involved in the severity of the pathology could also be
      beneficial in SCD. This study aimed to determine if 8 weeks of increased physical
      activity (PA) by voluntary wheel running affects the hypoxia/reoxygenation (H/R)
      responses by reducing oxidative stress and increasing NO synthesis in sickle SAD
      mice. Nitrite/nitrate (NOx) concentrations, NOS3 mRNA expression and
      phosphorylated-endothelial nitric oxide synthase immunostaining were increased in
      the lungs of the PA groups after H/R stress. Moreover, lipid peroxidation in the
      heart was decreased in PA SAD mice. The improvement of antioxidant activity at
      rest and the decrease in haemolysis may explain this reduced oxidative stress.
      These results suggest that physical activity probably diminishes some deleterious
      effects of H/R stress in SAD mice and could be protective against vascular
      occlusions.

PMID- 25382269
TI  - Unraveling the interactive effects of climate change and oil contamination on
      laboratory-simulated estuarine benthic communities.
AB  - There is growing concern that modifications to the global environment such as
      ocean acidification and increased ultraviolet radiation may interact with
      anthropogenic pollutants to adversely affect the future marine environment.
      Despite this, little is known about the nature of the potential risks posed by
      such interactions. Here, we performed a multifactorial microcosm experiment to
      assess the impact of ocean acidification, ultraviolet B (UV-B) radiation and oil
      hydrocarbon contamination on sediment chemistry, the microbial community
      (composition and function) and biochemical marker response of selected indicator
      species. We found that increased ocean acidification and oil contamination in the
      absence of UV-B will significantly alter bacterial composition by, among other
      things, greatly reducing the relative abundance of Desulfobacterales, known to be
      important oil hydrocarbon degraders. Along with changes in bacterial composition,
      we identified concomitant shifts in the composition of oil hydrocarbons in the
      sediment and an increase in oxidative stress effects on our indicator species.
      Interestingly, our study identifies UV-B as a critical component in the
      interaction between these factors, as its presence alleviates harmful effects
      caused by the combination of reduced pH and oil pollution. The model system used
      here shows that the interactive effect of reduced pH and oil contamination can
      adversely affect the structure and functioning of sediment benthic communities,
      with the potential to exacerbate the toxicity of oil hydrocarbons in marine
      ecosystems. 

PMID- 25382270
TI  - Design and synthesis of fluorescent 7-deazaadenosine nucleosides containing pi
      extended diarylacetylene motifs.
AB  - C-modified 7-deazaadenosines containing a diphenylacetylene moiety have been
      synthesised using cross-coupling approaches. The C-modified nucleosides exhibit
      remarkable fluorescence properties, including high quantum yields. Solvatochromic
      studies show a near linear correlation between the Stokes shift and solvent
      polarity which is indicative of intramolecular charge transfer. DFT calculations
      have allowed us to correlate the experimentally observed photophysical properties
      with the calculated HOMO-LUMO energy gaps within a series of real and model
      compounds. 

PMID- 25382271
TI  - InAs nanowire MOSFETs in three-transistor configurations: single balanced RF down
      conversion mixers.
AB  - Integration of III-V semiconductors on Si substrates allows for the realization
      of high-performance, low power III-V electronics on the Si-platform. In this
      work, we demonstrate the implementation of single balanced down-conversion mixer
      circuits, fabricated using vertically aligned InAs nanowire devices on Si. A
      thin, highly doped InAs buffer layer has been introduced to reduce the access
      resistance and serve as a bottom electrode. Low-frequency voltage conversion gain
      is measured up to 7 dB for a supply voltage of 1.5V. Operation of these mixers
      extends into the GHz regime with a -3 dB cut-off frequency of 2 GHz, limited by
      the optical lithography system used. The circuit dc power consumption is measured
      at 3.9 mW.

PMID- 25382272
TI  - An optimized table-top small-angle X-ray scattering set-up for the nanoscale
      structural analysis of soft matter.
AB  - The paper shows how a table top superbright microfocus laboratory X-ray source
      and an innovative restoring-data algorithm, used in combination, allow to analyze
      the super molecular structure of soft matter by means of Small Angle X-ray
      Scattering ex-situ experiments. The proposed theoretical approach is aimed to
      restore diffraction features from SAXS profiles collected from low scattering
      biomaterials or soft tissues, and therefore to deal with extremely noisy
      diffraction SAXS profiles/maps. As biological test cases we inspected: i)
      residues of exosomes' drops from healthy epithelial colon cell line and
      colorectal cancer cells; ii) collagen/human elastin artificial scaffolds
      developed for vascular tissue engineering applications; iii) apoferritin protein
      in solution. Our results show how this combination can provide
      morphological/structural nanoscale information to characterize new artificial
      biomaterials and/or to get insight into the transition between healthy and
      pathological tissues during the progression of a disease, or to morphologically
      characterize nanoscale proteins, based on SAXS data collected in a room-sized
      laboratory. 

PMID- 25382273
TI  - Boys who are born preterm show a relative lack of fat-free mass at 5 years of age
      compared to their peers.
AB  - AIM: Prematurity is associated with features of metabolic syndrome in young
      adulthood. We investigated the body composition and blood pressure of children
      born preterm. METHODS: A longitudinal, observational study was conducted with
      preterm infants who had a birth weight of <1500 g and a gestational age of <32
      weeks. Growth and body composition were assessed by air displacement
      plethysmography at term equivalent age and at school age and were compared to
      those of 61 healthy, term breastfed subjects. RESULTS: A total of 63 preterm
      infants were enrolled. At term equivalent age, growth and fat-free mass were
      lower in preterm infants than in term newborns, but fat mass was higher. At 5
      years of age, children born preterm were still lighter and shorter than children
      born at term. When the results were analysed by gender, the fat-free mass index
      was lower in boys born preterm than in their peers (12.1 +/- 1.1 versus 13.0 +/-
      1.0 kg/h(2) p < 0.005), whereas no difference was detected among girls. Diastolic
      blood pressure was higher in children born preterm than in children born at term
      (61.14 +/- 7.8 vs 56.69 +/- 8.2 mmHg, p = 0.009). CONCLUSION: Boys born preterm
      showed a relative lack of fat-free mass at school age compared to their peers.

PMID- 25382274
TI  - Current serological possibilities for the diagnosis of arthritis with special
      focus on proteins and proteoglycans from the extracellular matrix.
AB  - This review discusses our current understanding of how the expression and
      turnover of components of the cartilage extracellular matrix (ECM) have been
      investigated, both as molecular markers of arthritis and as indicators of disease
      progression. The cartilage ECM proteome is well studied; it contains
      proteoglycans (aggrecan, perlecan and inter-alpha-trypsin inhibitor), collagens
      and glycoproteins (cartilage oligomeric matrix protein, fibronectin and lubricin)
      that provide the structural and functional changes in arthritis. However, the
      changes that occur in the carbohydrate structures, including glycosaminoglycans,
      with disease are less well studied. Investigations of the cartilage ECM proteome
      have revealed many potential biomarkers of arthritis. However, a clinical
      diagnostic or multiplex assay is yet to be realized due to issues with
      specificity to the pathology of arthritis. The future search for clinical
      biomarkers of arthritis is likely to involve both protein and carbohydrate
      markers of the ECM through the application of glycoproteomics. 

PMID- 25382275
TI  - Potential of a tomato MAGIC population to decipher the genetic control of
      quantitative traits and detect causal variants in the resequencing era.
AB  - Identification of the polymorphisms controlling quantitative traits remains a
      challenge for plant geneticists. Multiparent advanced generation intercross
      (MAGIC) populations offer an alternative to traditional linkage or association
      mapping populations by increasing the precision of quantitative trait loci (QTL)
      mapping. Here, we present the first tomato MAGIC population and highlight its
      potential for the valorization of intraspecific variation, QTL mapping and causal
      polymorphism identification. The population was developed by crossing eight
      founder lines, selected to include a wide range of genetic diversity, whose
      genomes have been previously resequenced. We selected 1536 SNPs among the 4
      million available to enhance haplotype prediction and recombination detection in
      the population. The linkage map obtained showed an 87% increase in recombination
      frequencies compared to biparental populations. The prediction of the haplotype
      origin was possible for 89% of the MAGIC line genomes, allowing QTL detection at
      the haplotype level. We grew the population in two greenhouse trials and detected
      QTLs for fruit weight. We mapped three stable QTLs and six specific of a
      location. Finally, we showed the potential of the MAGIC population when coupled
      with whole genome sequencing of founder lines to detect candidate SNPs underlying
      the QTLs. For a previously cloned QTL on chromosome 3, we used the predicted
      allelic effect of each founder and their genome sequences to select putative
      causal polymorphisms in the supporting interval. The number of candidate
      polymorphisms was reduced from 12 284 (in 800 genes) to 96 (in 54 genes),
      including the actual causal polymorphism. This population represents a new
      permanent resource for the tomato genetics community. 

PMID- 25382276
TI  - A critical ethnography of communication processes involving the management of
      oral chemotherapeutic agents by patients with a primary diagnosis of colorectal
      cancer: study protocol.
AB  - AIM: To describe the protocol used to examine the processes of communication
      between health professionals, patients and informal carers during the management
      of oral chemotherapeutic medicines to identify factors that promote or inhibit
      medicine concordance. BACKGROUND: Ideally communication practices about oral
      medicines should incorporate shared decision-making, two-way dialogue and an
      equality of role between practitioner and patient. While there is evidence that
      healthcare professionals are adopting these concordant elements in general
      practice there are still some patients who have a passive role during
      consultations. Considering oral chemotherapeutic medications, there is a paucity
      of research about communication practices which is surprising given the high risk
      of toxicity associated with chemotherapy. DESIGN: A critical ethnographic design
      will be used, incorporating non-participant observations, individual semi
      structured and focus-group interviews as several collecting methods. METHODS:
      Observations will be carried out on the interactions between healthcare
      professionals (physicians, nurses and pharmacists) and patients in the outpatient
      departments where prescriptions are explained and supplied and on follow-up
      consultations where treatment regimens are monitored. Interviews will be
      conducted with patients and their informal carers. Focus-groups will be carried
      out with healthcare professionals at the conclusion of the study. These several
      will be analysed using thematic analysis. This research is funded by the
      Department for Employment and Learning in Northern Ireland (Awarded February
      2012). DISCUSSION: Dissemination of these findings will contribute to the
      understanding of issues involved when communicating with people about oral
      chemotherapy. It is anticipated that findings will inform education, practice and
      policy.

PMID- 25382277
TI  - PLS/OPLS models in metabolomics: the impact of permutation of dataset rows on the
      K-fold cross-validation quality parameters.
AB  - Among all the software packages available for discriminant analyses based on
      projection to latent structures (PLS-DA) or orthogonal projection to latent
      structures (OPLS-DA), SIMCA (Umetrics, Umea Sweden) is the more widely used in
      the metabolomics field. SIMCA proposes many parameters or tests to assess the
      quality of the computed model (the number of significant components, R2, Q2, pCV
      ANOVA, and the permutation test). Significance thresholds for these parameters
      are strongly application-dependent. Concerning the Q2 parameter, a significance
      threshold of 0.5 is generally admitted. However, during the last few years, many
      PLS-DA/OPLS-DA models built using SIMCA have been published with Q2 values lower
      than 0.5. The purpose of this opinion note is to point out that, in some
      circumstances frequently encountered in metabolomics, the values of these
      parameters strongly depend on the individuals that constitute the validation
      subsets. As a result of the way in which the software selects members of the
      calibration and validation subsets, a simple permutation of dataset rows can, in
      several cases, lead to contradictory conclusions about the significance of the
      models when a K-fold cross-validation is used. We believe that, when Q2 values
      lower than 0.5 are obtained, SIMCA users should at least verify that the quality
      parameters are stable towards permutation of the rows in their dataset.

PMID- 25382278
TI  - Protein thiols undergo reversible and irreversible oxidation during chill storage
      of ground beef as detected by 4,4'-dithiodipyridine.
AB  - Quantification of protein thiols and disulfides in ground beef during storage
      under high-oxygen atmosphere at 4  degrees C was performed by thiol detection
      using 4,4'-dithiodipyridine (4-DPS) before and after disulfide reduction using
      sodium borohydride. Two independent storage trials were performed, and in trial
      1, only reversible thiol oxidation was observed (thiol loss was 30%). In trial 2,
      irreversible thiol oxidation occurred during the first days of storage, while
      further loss of thiols was caused by reversible disulfide formation (thiol loss
      was 33%, of which ca. half was lost because of irreversible oxidation). The
      results were compared to sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis of cross-linked myosin heavy chain formed by
      disulfide bonding. Both methods confirmed increasing disulfide formation because
      of thiol oxidation in meat during storage, but the 4-DPS method showed higher
      disulfide percentages than the SDS-PAGE method (22.2 +/- 0.3% and 8.5 +/- 1.2%,
      respectively). The 4-DPS assay provides an accurate method to evaluate the thiol
      disulfide redox state in meat. 

PMID- 25382279
TI  - Thrombin Causes Neuronal Atrophy and Acute but not Chronic Cell Death.
AB  - BACKGROUND: Brain injury after intracerebral hemorrhage (ICH) arises from
      numerous contributors, of which some also play essential roles. Notably, thrombin
      production, needed to stop bleeding, also causes acute cell death and edema. In
      some rodent models of ICH, peri-hematoma neurons die over weeks. Hence we
      evaluated whether thrombin is responsible for this chronic degeneration.
      Functional impairments after ICH also result from sub-lethal damage to neurons,
      especially the loss of dendrites. Thus, we evaluated whether thrombin infusion
      alone, a reductionist model of ICH, causes similar injury. METHODS: Adult rats
      had a modest intra-striatal infusion of thrombin (1 U) or saline followed by a
      behavioral test, to verify impairment, 7 days later. After this they were
      euthanized and tissue stained with Golgi-Cox solution to allow the assessment of
      dendritic morphology in striatal neurons. In a second experiment, rats survived 7
      or 60 days after thrombin infusion in order to histologically determine lesion
      volume. RESULTS: Thrombin caused early cell death and considerable atrophy in
      surviving peri-lesion neurons, which had less than half of their usual numbers of
      branches. However, total tissue loss was comparable at 7 (24.1 mm3) and 60 days
      (25.6 mm3). CONCLUSION: Thrombin infusion causes early cell death and neuronal
      atrophy in nearby surviving striatal neurons but thrombin does not cause chronic
      tissue loss. Thus, the chronic degeneration found after ICH in rats is not simply
      and solely due to acute thrombin production. Nonetheless, thrombin is an
      important contributor to behavioral dysfunction because it causes cell death and
      substantial dendritic injury.

PMID- 25382281
TI  - Social support improves mental health among the victims relocated to temporary
      housing following the Great East Japan Earthquake and Tsunami.
AB  - The victims of the Great East Japan Earthquake and Tsunami have been forced to
      live in temporary housing, mainly by two different methods of resettlement: group
      allocation that preserved pre-existing local social ties and lottery allocation.
      We examined the effects of various factors, including the resettlement methods
      and social support, on mental health. From February to March 2012, we completed a
      cross-sectional survey of 281 refugees aged 40 years or older, who had lost their
      homes in the tsunami and were living in temporary housing in Iwanuma city.
      Psychological distress of the victims was assessed using the Kessler
      Psychological Distress Scale (K6) that consists of six self-reported items.
      Participants were also asked whether they had provided or received social support
      during this time. Participants were categorized as "providing social support" if
      they listened to someone else's concerns and complaints, or "receiving social
      support" if they have someone who listened to their concerns and complaints.
      After adjusting for age and sex, multiple log-binomial regression analysis showed
      that participants without social support had a higher risk of psychological
      distress. Group allocation victims were more likely to receive social support
      than those who underwent lottery allocation. However, the resettlement approach
      did not significantly correlate with distress. Other factors associated with a
      higher risk of psychological distress were a younger age (55 or younger), living
      with either 3 people or 6 or more people, and having a lower income. The present
      results suggest that social support promotes the mental health of disaster
      victims. 

PMID- 25382280
TI  - The many weak instruments problem and Mendelian randomization.
AB  - Instrumental variable estimates of causal effects can be biased when using many
      instruments that are only weakly associated with the exposure. We describe
      several techniques to reduce this bias and estimate corrected standard errors. We
      present our findings using a simulation study and an empirical application. For
      the latter, we estimate the effect of height on lung function, using genetic
      variants as instruments for height. Our simulation study demonstrates that, using
      many weak individual variants, two-stage least squares (2SLS) is biased, whereas
      the limited information maximum likelihood (LIML) and the continuously updating
      estimator (CUE) are unbiased and have accurate rejection frequencies when
      standard errors are corrected for the presence of many weak instruments. Our
      illustrative empirical example uses data on 3631 children from England. We used
      180 genetic variants as instruments and compared conventional ordinary least
      squares estimates with results for the 2SLS, LIML, and CUE instrumental variable
      estimators using the individual height variants. We further compare these with
      instrumental variable estimates using an unweighted or weighted allele score as
      single instruments. In conclusion, the allele scores and CUE gave consistent
      estimates of the causal effect. In our empirical example, estimates using the
      allele score were more efficient. CUE with corrected standard errors, however,
      provides a useful additional statistical tool in applications with many weak
      instruments. The CUE may be preferred over an allele score if the population
      weights for the allele score are unknown or when the causal effects of multiple
      risk factors are estimated jointly.

PMID- 25382283
TI  - Clinical implications of basic science discoveries: janus resurrected--two faces
      of B cell and plasma cell biology.
AB  - B cells play a complex role in the immune response. In addition to giving rise to
      plasma cells (PCs) and promoting T cell responses via antigen presentation, they
      perform immunoregulatory functions. This knowledge has created concerns regarding
      nonspecific B cell depletional therapy because of the potential to paradoxically
      augment immune responses. Recent studies now indicate that PCs have immune
      functions beyond immunoglobulin synthesis. Evidence for a new role for PCs as
      potent regulatory cells (via IL-10 and IL-35 production) is discussed including
      the implications for PC-targeted therapies currently being developed for clinical
      transplantation. 

PMID- 25382290
TI  - Type A and AB thymomas: histological features associated with increased stage.
AB  - AIMS: The current WHO classification of thymic epithelial neoplasms describes
      type A and type AB thymomas as behaving 'like benign neoplasms'. However, recent
      published data suggest that rare cases may show more aggressive behaviour. The
      aim of this study was to assess the frequency of atypical cases, and to determine
      whether atypia is associated with more advanced disease. METHODS AND RESULTS: One
      hundred and twenty-one thymomas (type A, n = 68; type AB, n = 53) were
      retrospectively reviewed for 'atypical' features (nuclear pleomorphism, mitotic
      activity, and necrosis). Logistic regression was used to ascertain the
      association with increasing Masaoka-Koga stage. Where available, follow-up data
      were also reviewed. There were 72 stage I, 42 stage II, five stage III and two
      stage IV tumours. Only the presence of necrosis showed a significant association
      with increased stage in univariate and multivariate analysis. Nuclear atypia and
      increased mitotic activity were not associated with increasing stage of disease.
      CONCLUSIONS: Our data support the concept of there being more aggressive atypical
      variants of both type A and type AB thymoma, and suggest that the presence of
      necrosis could be used to predict aggressive behaviour.

PMID- 25382291
TI  - An investigation of matching symmetry in the human pinnae with possible
      implications for 3D ear recognition and sound localization.
AB  - The human external ears, or pinnae, have an intriguing shape and, like most parts
      of the human external body, bilateral symmetry is observed between left and
      right. It is a well-known part of our auditory sensory system and mediates the
      spatial localization of incoming sounds in 3D from monaural cues due to its shape
      specific filtering as well as binaural cues due to the paired bilateral locations
      of the left and right ears. Another less broadly appreciated aspect of the human
      pinna shape is its uniqueness from one individual to another, which is on the
      level of what is seen in fingerprints and facial features. This makes pinnae very
      useful in human identification, which is of great interest in biometrics and
      forensics. Anatomically, the type of symmetry observed is known as matching
      symmetry, with structures present as separate mirror copies on both sides of the
      body, and in this work we report the first such investigation of the human pinna
      in 3D. Within the framework of geometric morphometrics, we started by
      partitioning ear shape, represented in a spatially dense way, into patterns of
      symmetry and asymmetry, following a two-factor anova design. Matching symmetry
      was measured in all substructures of the pinna anatomy. However, substructures
      that 'stick out' such as the helix, tragus, and lobule also contained a fair
      degree of asymmetry. In contrast, substructures such as the conchae, antitragus,
      and antihelix expressed relatively stronger degrees of symmetric variation in
      relation to their levels of asymmetry. Insights gained from this study were
      injected into an accompanying identification setup exploiting matching symmetry
      where improved performance is demonstrated. Finally, possible implications of the
      results in the context of ear recognition as well as sound localization are
      discussed. 

PMID- 25382292
TI  - Post-concussive symptoms and neuropsychological performance in the post-acute
      period following pediatric mild traumatic brain injury.
AB  - OBJECTIVE: There is evidence that children after mild traumatic brain injuries
      (mTBI) suffer ongoing post-concussive symptoms (PCS). However, results concerning
      neuropsychological outcome after mTBI are controversial. Thus, our aim was to
      examine group differences regarding neuropsychological outcome and PCS.
      Additionally, we explored the influence of current and pre-injury everyday
      attention problems on neuropsychological outcome in children after mTBI. METHOD:
      In a prospective short-term longitudinal study, 40 children (aged 6-16 years)
      after mTBI and 38 children after orthopedic injury (OI) underwent
      neuropsychological, socio-behavioral and PCS assessments in the acute stage and
      at 1 week, at 4 weeks, and 4 months after the injury. RESULTS: Parents of
      children after mTBI observed significantly more PCS compared to parents of
      children after OI, especially in the acute stage. Our results revealed no
      neuropsychological or socio-behavioral differences over time between both groups.
      However, in children after mTBI, we found negative correlations between elevated
      levels of everyday attention problems and reduced neuropsychological performance.
      Furthermore, there was a negative influence of pre-injury everyday attention
      problems on neuropsychological performance in children after mTBI. CONCLUSION: In
      accordance with earlier studies, parents of children after mTBI initially
      observed significantly more PCS compared to parents of children after OI. There
      were no neuropsychological or socio-behavioral group differences between children
      after mTBI and OI in the post-acute period. However, our exploratory findings
      concerning the influence of everyday attention problems on neuropsychological
      outcome indicate that current and pre-injury everyday attention problems were
      negatively associated with neuropsychological performance in children after mTBI.

PMID- 25382293
TI  - Helicobacter pylori Infection Increase the Risk of Myocardial Infarction: A Meta
      Analysis of 26 Studies Involving more than 20,000 Participants.
AB  - BACKGROUND: Myocardial infarction is a fatal cardiovascular disease and one of
      the most common death causes all around the world. The aim of the meta-analysis
      was to quantify the risk of myocardial infarction associated with Helicobacter
      pylori infection. METHODS: A literature search was performed to identify studies
      published before 14 July, 2014, for relevant risk estimates. Fixed and random
      effect meta-analytical techniques were conducted for myocardial infarction.
      RESULTS: Twenty-six case-control studies involving 5829 myocardial infarction
      patients and more than 16,000 controls were included. Helicobacter pylori
      infection was associated with an increased risk of myocardial infarction (OR:
      2.10, 95%CI: 1.75-2.53, p = .06). We also discovered a significant association
      between the bacteria and risk of myocardial infarction in young people (OR: 1.93,
      95% CI: 1.41-2.66, p = .07), in elder people (OR: 2.02, 95% CI: 1.60-2.54, p =
      .29), in Caucasians (OR: 2.29, 95% CI: 1.99-2.63, p = .12), and in Asians (OR:
      1.75, 95% CI: 1.12-2.73, p = .08). CONCLUSION: Our meta-analyses suggested a
      possible indication of relationship between Helicobacter pylori infection and the
      risk of myocardial infarction. The pathogenicity might not be affected by age and
      race. More researches should be conducted to explore the mechanisms involved.

PMID- 25382294
TI  - A Transitional Model for the Evaluation of West Nile Virus Transmission in Italy.
AB  - In August 2008, after 10 years of apparent silence, West Nile virus (WNV)
      infection re-emerged in northern Italy, spreading through the territories of
      three regions. In the following years, new cases occurred in the same area and
      additional foci of infection were observed in central and southern Italy,
      involving also Sicily and Sardinia islands. The Italian Ministry of Health
      ordered to test by RT-PCR all blood and organ donors from 15th June to 15th
      November of each year in the infected areas. The period at risk of WNV
      transmission was defined on the basis of literature data, but a more scientific
      estimation of the transmission season, under Italian circumstances, needs to be
      performed. A transitional model previously developed by other Authors was applied
      and adapted to Italian circumstances, to describe and quantify the WNV
      transmission cycle between birds and mosquitoes. Culex spp. was considered the
      main vector, and mosquito parameters were adapted to this genus. Magpies (Pica
      pica) were considered the main bird host. The model was partially validated
      through the results of the entomological surveys carried out in central Italy and
      in Po Valley. The results of the transitional model permitted to calculate the
      basic reproduction number (R0 ) during 2010 for the whole Italian territory at 1
      km of spatial resolution, estimating the risk of WNV transmission during the year
      and creating detailed risk maps for Italy. The mean values of R0 for the whole
      Italy varied between 0.4 and 4.8, with values >1 from the end of May to the
      middle of September. The coastal and flat zones of Italy showed the highest R0
      values. Although partially validated, the model showed a substantial acceptable
      capacity of defining the period at major risk of WNV transmission in Italy,
      helping Public health authorities in the application of appropriate and timely
      control and preventive measures. 

PMID- 25382295
TI  - Temporal variation in mycorrhizal diversity and carbon and nitrogen stable
      isotope abundance in the wintergreen meadow orchid Anacamptis morio.
AB  - Many adult orchids, especially photoautotrophic species, associate with a diverse
      range of mycorrhizal fungi, but little is known about the temporal changes that
      might occur in the diversity and functioning of orchid mycorrhiza during
      vegetative and reproductive plant growth. Temporal variations in the spectrum of
      mycorrhizal fungi and in stable isotope natural abundance were investigated in
      adult plants of Anacamptis morio, a wintergreen meadow orchid. Anacamptis morio
      associated with mycorrhizal fungi belonging to Tulasnella, Ceratobasidium and a
      clade of Pezizaceae (Ascomycetes). When a complete growing season was
      investigated, multivariate analyses indicated significant differences in the
      mycorrhizal fungal community. Among fungi identified from manually isolated
      pelotons, Tulasnella was more common in autumn and winter, the pezizacean clade
      was very frequent in spring, and Ceratobasidium was more frequent in summer. By
      contrast, relatively small variations were found in carbon (C) and nitrogen (N)
      stable isotope natural abundance, A. morio samples showing similar (15)N
      enrichment and (13)C depletion at the different sampling times. These
      observations suggest that, irrespective of differences in the seasonal
      environmental conditions, the plant phenological stages and the associated fungi,
      the isotopic content in mycorrhizal A. morio remains fairly constant over time.

PMID- 25382296
TI  - A cyano-bridged tubular coordination polymer with dominant ferromagnetic
      interactions.
AB  - It is a challenge to synthesize a porous tubular coordination polymer with
      magnetic properties. Utilizing [Fe(II)(bipy)(CN)4](2-) (bipy = 2,2'-bipyridine)
      as the building block to react with Mn(2+), we successfully synthesized a cyano
      bridged tubular coordination polymer with dominant ferromagnetic interactions.
      The inner surface of the heterometallic tube is hydrophilic, whereas the outer
      surface is hydrophobic. The framework is stable up to 320  degrees C and can
      adsorb N2 and CO2. The ferromagnetic interactions were transmitted via the
      diamagnetic N-C-Fe(II)-C-N species between Mn(2+) ions in the tube. 

PMID- 25382300
TI  - Toll-like receptor agonist lipopeptides self-assemble into distinct
      nanostructures.
AB  - The self-assembled structure of toll-like receptor agonist lipopeptides
      containing the CSK4 peptide sequence is examined in aqueous solution. A
      remarkable dependence of morphology on the number of attached hexadecyl lipid
      chains is demonstrated, with spherical micelle structures for mono- and di
      lipidated structures observed, but flexible wormlike micelles for the homologue
      containing three lipid chains. The distinct modes of assembly may have an
      important influence on the bioactivity of this class of lipopeptide. 

PMID- 25382301
TI  - Impact of human albumin infusion on organ function in orthotopic liver
      transplantation--a retrospective matched-pair analysis.
AB  - BACKGROUND: The purpose of this study was to retrospectively analyze the impact
      of human albumin (HA) substitution on organ function in patients undergoing
      orthotopic liver transplantation (OLT). METHODS: We retrospectively analyzed
      chart data of 15 hypoalbuminemic patients who received continuous infusion of HA
      (100 g/d) for seven d following OLT and matched them with 15 control patients for
      severity scores at admission. Primary endpoint was a difference in mean
      "sequential organ failure assessment" (SOFA) score during 14 d following OLT.
      Secondary endpoints included SOFA subscores, length of intensive care unit (ICU)
      stay, ICU mortality, one-yr mortality, fluid balance, colloid osmotic pressure
      (COP), serum albumin, and total protein concentrations. RESULTS: Substitution of
      HA was associated with a lower mean SOFA score as compared to control (11.0 +/-
      3.6 vs. 13.4 +/- 3.7; p < 0.001). Patients treated with HA also exhibited lower
      cardiovascular SOFA subscore and higher COP, serum albumin, and total protein
      concentrations. There were no significant differences in fluid balance, length of
      ICU stay, ICU mortality, or one-yr mortality. CONCLUSIONS: The present data
      suggest that continuous infusion of HA may preserve cumulative organ function (as
      measured by SOFA score) with emphasis on cardiovascular function in patients
      following OLT.

PMID- 25382302
TI  - Isolation of achyrobichalcone from Achyrocline satureioides by high- speed
      countercurrent chromatography.
AB  - Achyrobichalcone is a biflavonoid recently found in Achyrocline satureioides.
      This substance has unprecedented chemical structure and occurrence, but resembles
      other bioactive bichalcones, which have important pharmacological properties,
      such as anticancer activity. The major challenge for evaluation of the
      physicochemical and biological properties of this new molecule is the isolation
      step, which affects the purity and yield of the isolated product. Thus, the
      objective of this work was to develop a semi-preparative method for
      achyrobichalcone isolation from Achyrocline satureioides by high-speed
      countercurrent chromatography. The high-speed countercurrent chromatography
      separation was achieved in two steps. In the first step, an enriched fraction of
      achyrobichalcone from the freeze-dried extract was obtained, using the solvent
      system hexane-ethyl acetate-methanol-water 0.8:1:0.8:1, v/v. The purification of
      achyrobichalcone from the enriched fractions was achieved by further high-speed
      countercurrent chromatography fractionation with hexane-ethyl acetate-methanol
      water 0.9:0.9:0.8:1, v/v. The final isolated product was obtained using
      preparative thin layer chromatography and crystallization procedure. A yellow
      semi-crystalline solid with purity close to 90% was obtained as the final
      product. The mass recovery of achyrobichalcone isolation was near 67%. The
      structural identification from spectroscopic and chromatographic techniques
      confirmed the achyrobichalcone structure. This is the first report of
      achyrobichalcone isolation on a semi-preparative scale by high-speed
      countercurrent chromatography. This method afforded achyrobichalcone in good
      yield and purity for further biopharmaceutical studies. 

PMID- 25382303
TI  - Luteolin antagonizes angiotensin II-dependent proliferation and collagen
      synthesis of cultured rat cardiac fibroblasts.
AB  - OBJECTIVE: The purpose of this study was to observe if luteolin could affect the
      behavior of cardiac fibroblasts (CFs) on myocardial fibrosis stimulated by
      angiotensin II (Ang II) and investigate the mechanism involved. METHODS: MTT was
      used to observe the CFs viability and proliferation which was also detected by an
      EdU staining kit. Cell migration was determined by the transwell chamber. Western
      blotting was used to examine the protein expression levels of a smooth muscle
      actin (alpha-SMA), collagen I and collagen III. The activity of nitric oxide
      (NO), synthase (NOS), nitrite and cyclic GMP (cGMP) content were measured
      according to the kits and an enzyme linked immunosorbent assay (ELISA)
      respectively. RESULTS: The proliferation, migration and expression of alpha-SMA,
      collagen I and collagen III in CFs stimulated by Ang II were inhibited by
      luteolin treatment, and these effects were partly blocked by a combination of
      treatment with Ang II and NG-nitro-Larginine methyl ester (L-NAME), a non
      selective NOS inhibitor, also with 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one
      (ODQ), a specific inhibitor of guanylyl cyclase. These effects did not include
      CFs migration, which showed no apparent difference between Ang II single and
      together with inhibitors. Luteolin increased the synthesis of total NOS and the
      content of nitrite and cGMP. CONCLUSION: These results demonstrate that luteolin
      is capable of inhibiting the behavior of CFs stimulated by Ang II via up
      regulation of NO-cGMP signal pathway.

PMID- 25382304
TI  - In vitro effects of arylhydrocoumarin on free radicals and oxidative stress in
      erythrocytes and Saccharomyces cerevisiae.
AB  - Neoflavonoids comprise a group of natural compounds with varied chemical
      structures and promising pharmacological properties, including antioxidant
      capacity. This work describes an evaluation of the in vitro antioxidant capacity
      of a new coumarin derivative, i.e., 7-acetoxy-4-aryl-3,4-dihydrocoumarin, in
      terms of its ability to quench the 2,2- diphenyl-1-picrylhydrazyl (DPPH*), 2,2'
      azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+), hydroxyl (OH*) and
      superoxide anion (O2(*-)) radicals, as well as its capacity to initiate electron
      transfer by reducing potential and inhibit lipid peroxidation by TBARS
      (thiobarbituric acid reactive substances) method. In addition, the antioxidant
      capacity of 7-acetoxy-4-aryl-3,4-dihydrocoumarin was evaluated against oxidative
      damage induced by hydrogen peroxide in erythrocyte suspensions and S. cerevisiae
      strains. In all methodologies investigated, high antioxidant capacities above 65%
      were demonstrated by 7-acetoxy-4-aryl-3,4-dihydrocoumarin against the DPPH(*),
      ABTS(*+), OH(*) and O2(*-) radicals. The ability of 7-acetoxy-4-aryl-3,4
      dihydrocoumarin to inhibit oxidative damage induced by hydrogen peroxide in
      erythrocytes and S. cerevisiae strains demonstrates the importance of this
      compound in the protection against oxidative stress at the cellular level. Thus,
      the results obtained in this study suggest that 7-acetoxy-4-aryl-3,4
      dihydrocoumarin can assist the development of new antioxidant products for
      possible use in the prevention or reduction of diseases related to oxidative
      stress. 

PMID- 25382305
TI  - Structure and stoichiometry prediction of surfaces reacting with multicomponent
      gases.
AB  - Reactive interactions of molecules with solid surfaces are of key interest for
      catalysis and surface functionalization. Here, conceptual shortcomings of
      previous theoretical methods for the prediction of steady-state surface
      structures and stoichiometries from first-principles thermodynamics are
      identified. An extension is then proposed, which now enables the unconstrained
      description of an arbitrary number of mutually reacting gas-phase species. 

PMID- 25382307
TI  - Time- and state-dependent analysis of autonomic control in narcolepsy: higher
      heart rate with normal heart rate variability independent of sleep fragmentation.
AB  - Narcolepsy with hypocretin deficiency is known to alter cardiovascular control
      during sleep, but its aetiology is disputed. As cardiovascular control differs
      between sleep states, and narcolepsy affects sleep architecture, controlling for
      both duration and transitions of sleep states is necessary. This study therefore
      aimed to assess heart rate and its variability in narcolepsy during sleep taking
      these factors into account. The study included 12 medication-naive patients with
      narcolepsy with cataplexy and hypocretin deficiency (11 male, 16-53 years old),
      and 12 sex- and age-matched healthy controls (11 male, 19-55 years). All subjects
      underwent 1-night ambulatory polysomnography recording. Cardiovascular parameters
      were calculated for each 30-s epoch. Heart rate was significantly higher in
      patients with narcolepsy than in controls in all sleep states and during
      wakefulness prior to sleep. Groups did not differ in heart rate variability
      measures. The effects of sleep state duration on heart rate and its variability
      were similar between patients and controls. In conclusion, heart rate was
      consistently higher in patients with narcolepsy than controls, independent of
      sleep stage and sleep fragmentation. A direct effect of hypocretin deficiency
      therefore seems probable.

PMID- 25382308
TI  - Large ultrathin shelled drops produced via non-confined microfluidics.
AB  - We present a facile approach for producing large and monodisperse core-shell
      drops with ultrathin shells using a single-step process. A biphasic compound jet
      is introduced into a quiescent third (outer) phase that ruptures to form core
      shell drops. Ultrathin shelled drops could only be produced within a certain
      range of surfactant concentrations and flow rates, highlighting the effect of
      interfacial tension in engulfing the core in a thin shell. An increase in
      surfactant concentrations initially resulted in drops with thinner shells.
      However, the drops with thinnest shells were obtained at an optimum surfactant
      concentration, and a further increase in the surfactant concentrations increased
      the shell thickness. Highly monodisperse (coefficient of variation smaller than 3
      %) core-shell drops with diameter of ~200 MUm-2 mm with shell thickness as small
      as ~2 MUm were produced. The resulting drops were stable enough to undergo
      polymerisation and produce ultrathin shelled capsules. 

PMID- 25382306
TI  - Prostacyclin suppresses twist expression in the presence of indomethacin in bone
      marrow-derived mesenchymal stromal cells.
AB  - BACKGROUND: Iloprost, a stable prostacyclin I2 analogue, seems to have an
      osteoblast-protective potential, whereas indomethacin suppresses new bone
      formation. The aim of this study was to investigate human bone marrow stromal
      cell (BMSC) proliferation and differentiation towards the osteoblastic lineage by
      administration of indomethacin and/or iloprost. MATERIAL/METHODS: Human bone
      marrow cells were obtained from 3 different donors (A=26 yrs/m; B=25 yrs/f, C=35
      yrs/m) via vacuum aspiration of the iliac crest followed by density gradient
      centrifugation and flow cytometry with defined antigens (CD105+/73+/45-/14-). The
      cells were seeded and incubated as follows: without additives (Group 0; donor
      A/B/C), with 10(-7) M iloprost only (Group 0+ilo; A/B), with indomethacin only in
      concentrations of 10(-6) M (Group 1, A), 10(-5) M (Group 2, B), 10(-4) M (Group
      3, A/B), and together with 10(-7) M iloprost (Groups 4-6, A/B/C). On Day 10 and
      28, UV/Vis spectrometric and immunocytochemical assays (4 samples per group and
      donor) were performed to investigate cell proliferation (cell count measurement)
      and differentiation towards the osteoblastic lineage (CD34-, CD45-, CD105+, type
      1 collagen (Col1), osteocalcin (OC), alkaline phosphatase (ALP), Runx2, Twist,
      specific ALP-activity). RESULTS: Indomethacin alone suppressed BMSC
      differentiation towards the osteoblastic lineage by downregulation of Runx2,
      Col1, and ALP. In combination with indomethacin, iloprost increased cell
      proliferation and differentiation and it completely suppressed Twist expression
      at Day 10 and 28. Iloprost alone did not promote cell proliferation, but
      moderately enhanced Runx2 and Twist expression. However, the proliferative
      effects and the specific ALP-activity varied donor-dependently. CONCLUSIONS:
      Iloprost partially antagonized the suppressing effects of indomethacin on BMSC
      differentiation towards the osteoblast lineage. It enhanced the expression of
      Runx2 and, only in the presence of indomethacin, it completely suppressed Twist.
      Thus, in the treatment of avascular osteonecrosis or painful bone marrow edema,
      the undesirable effects of indomethacin might be counterbalanced by iloprost.

PMID- 25382309
TI  - Cutaneous B-lymphoblastic lymphoma with IL3/IgH translocation presenting with
      hypereosinophilia and acute endocarditis.
AB  - Hypereosinophilia is a rare phenomenon associated with childhood malignancy,
      predominantly acute lymphoblastic leukaemia. Causation is unclear and likely to
      have multiple mechanisms. We report a six year old boy presenting with
      hypereosinophilia and associated Loeffler endocarditis. Three months following
      his initial hypereosinophilia he developed cutaneous B-lymphoblastic lymphoma. Re
      analysis of apparently uninvolved bone marrow, taken at initial presentation,
      revealed a single, previously unidentified, t(5;14)(q31;q32) positive cell. Using
      fluorescent in situ hybridisation, we demonstrate IL3/IgH@ fusion in cutaneous
      lymphoma cells. Our case confirms the association of hypereosinophilia and B
      lymphoblastic lymphoma and strengthens the association between IL3 hypersecretion
      and hypereosinophilia.

PMID- 25382310
TI  - Expected degree for RNA secondary structure networks.
AB  - Consider the network of all secondary structures of a given RNA sequence, where
      nodes are connected when the corresponding structures have base pair distance
      one. The expected degree of the network is the average number of neighbors, where
      average may be computed with respect to the either the uniform or Boltzmann
      probability. Here, we describe the first algorithm, RNAexpNumNbors, that can
      compute the expected number of neighbors, or expected network degree, of an input
      sequence. For RNA sequences from the Rfam database, the expected degree is
      significantly less than the constrained minimum free energy structure, defined to
      have minimum free energy (MFE) over all structures consistent with the Rfam
      consensus structure. The expected degree of structural RNAs, such as purine
      riboswitches, paradoxically appears to be smaller than that of random RNA, yet
      the difference between the degree of the MFE structure and the expected degree is
      larger than that of random RNA. Expected degree does not seem to correlate with
      standard structural diversity measures of RNA, such as positional entropy and
      ensemble defect. The program RNAexpNumNbors is written in C, runs in cubic time
      and quadratic space, and is publicly available at
      http://bioinformatics.bc.edu/clotelab/RNAexpNumNbors.

PMID- 25382311
TI  - Molecular damage in Fabry disease: characterization and prediction of alpha
      galactosidase A pathological mutations.
AB  - Loss-of-function mutations of the enzyme alpha-galactosidase A (GLA) causes Fabry
      disease (FD), that is a rare and potentially fatal disease. Identification of
      these pathological mutations by sequencing is important because it allows an
      early treatment of the disease. However, before taking any treatment decision, if
      the mutation identified is unknown, we first need to establish if it is
      pathological or not. General bioinformatic tools (PolyPhen-2, SIFT, Condel, etc.)
      can be used for this purpose, but their performance is still limited. Here we
      present a new tool, specifically derived for the assessment of GLA mutations. We
      first compared mutations of this enzyme known to cause FD with neutral sequence
      variants, using several structure and sequence properties. Then, we used these
      properties to develop a family of prediction methods adapted to different quality
      requirements. Trained and tested on a set of known Fabry mutations, our methods
      have a performance (Matthews correlation: 0.56-0.72) comparable or better than
      that of the more complex method, Polyphen-2 (Matthews correlation: 0.61), and
      better than those of SIFT (Matthews correl.: 0.54) and Condel (Matthews correl.:
      0.51). This result is validated in an independent set of 65 pathological
      mutations, for which our method displayed the best success rate (91.0%, 87.7%,
      and 73.8%, for our method, PolyPhen-2 and SIFT, respectively). These data
      confirmed that our specific approach can effectively contribute to the
      identification of pathological mutations in GLA, and therefore enhance the use of
      sequence information in the identification of undiagnosed Fabry patients.

PMID- 25382313
TI  - Stereo- and regioselective phyllobilane oxidation in leaf homogenates of the
      peace lily (Spathiphyllum wallisii): hypothetical endogenous path to yellow
      chlorophyll catabolites.
AB  - Invited for the cover of this issue is the group of Bernhard Krautler at the
      University of Innsbruck, Austria. The image depicts the autumnal "disappearance"
      of chlorophyll and the ensuing rapid formation of colorless phyllobilins. Read
      the full text of the article at 10.1002/chem.201404783. 

PMID- 25382312
TI  - PARP13 regulates cellular mRNA post-transcriptionally and functions as a pro
      apoptotic factor by destabilizing TRAILR4 transcript.
AB  - Poly(ADP-ribose) polymerase-13 (PARP13/ZAP/ZC3HAV1) is an antiviral factor,
      active against specific RNA viruses such as murine leukaemia virus, Sindbis virus
      and human immunodeficiency virus. During infection, PARP13 binds viral RNA via
      its four CCCH-type zinc-finger domains and targets it for degradation by
      recruiting cellular messenger RNA (mRNA) decay factors such as the exosome
      complex and XRN1. Here we show that PARP13 binds to and regulates cellular mRNAs
      in the absence of viral infection. Knockdown of PARP13 results in the
      misregulation of hundreds of transcripts. Among the most upregulated transcripts
      is TRAILR4 that encodes a decoy receptor for TRAIL-a pro-apoptotic cytokine that
      is a promising target for the therapeutic inhibition of cancers. PARP13
      destabilizes TRAILR4 mRNA post-transcriptionally in an exosome-dependent manner
      by binding to a region in its 3' untranslated region. As a consequence, PARP13
      represses TRAILR4 expression and increases cell sensitivity to TRAIL-mediated
      apoptosis, acting as a key regulator of the cellular response to TRAIL. 

PMID- 25382314
TI  - Assessment of the statistical significance of classifications in infrared
      spectroscopy based diagnostic models.
AB  - Fourier transform infrared (IR) spectroscopy in combination with multivariate
      data analysis is a versatile tool that can be applied to disease diagnosis.
      However, a rigorous validation of the obtained models is necessary in order to
      obtain robust results. This work evaluates the advantages of the use of
      permutation testing for determining the statistical significance of the
      misclassification errors obtained from IR based diagnostic models through cross
      validation (CV). The model performance, estimated by CV, is compared to a
      distribution of CV-performance values obtained using randomly permuted class
      labels. The distribution of 'random CV-values' is considered as a null
      distribution and used to establish the significance of the model estimators
      obtained using real class labels. ATR-FTIR spectra of serum samples were
      classified using random forest (RF) classifiers according to two criteria, the
      tag number (a randomly assigned pseudo class membership) and the level of urea
      (real class). CV errors obtained were compared to the null distribution of CV
      errors from a permutation test and an independent validation set. The procedure
      was evaluated testing typical conditions leading to overoptimistic estimations
      provided by the CV like e.g. the size of subsamples used during CV, variable
      selection and the use of replicates. Results show that for the tag number (pseudo
      class), CV indicated classification errors between 23 and 33% depending on the
      subsample size employed. Those values were even lower when variable selection or
      replicates were used. However, permutation testing indicated that those CV errors
      were non-significant. In contrast, for sample classification according to their
      levels of urea, all cross validation errors were found to be significant.
      Although the proposed method is computationally intensive, it provides a simple
      way of calculating an empirical p-value of the CV-estimator, thus establishing
      the statistical significance and providing a feasibility indicator especially
      useful for studies where the number of samples is limited. 

PMID- 25382316
TI  - Molecular simulation and experimental study of CO2 absorption in ionic liquid
      reverse micelle.
AB  - The structure and dynamics for CO2 absorption in ionic liquid reverse micelle
      (ILRM) were studied using molecular simulations. The ILRM consisted of 1-butyl-3
      methylimidazolium tetrafluoroborate ([bmim][BF4]) ionic liquid (IL) as the
      micelle core, the benzylhexadecyldimethylammonium ([BHD](+)) chloride ([Cl](-))
      was the cationic surfactant, and benzene was used as the continuous solvent phase
      in this study. The diffusivity values of this ILRM system were also
      experimentally determined. Simulations indicate that there is ion exchange
      between the IL anion ([BF4](-)) and the surfactant anion ([Cl](-)). It was also
      found that the [bmim][BF4] IL exhibits small local density at the interface
      region between the IL core and the [BHD](+) surfactant cation layer, which leads
      to a smaller density for the [bmim][BF4] IL inside the reverse micelle (RM)
      compared with the neat IL. These simulation findings are consistent with
      experimental results. Both our simulations and experimental results show that
      [bmim][BF4] inside the RM diffuses 5-26 times faster than the neat IL, which is
      partly due to the fast particle diffusion for the ILRM nanodroplet (IL and
      surfactant) as a whole in benzene solvent compared with neat [bmim][BF4]
      diffusion. Additionally, it was found that [bmim][BF4] IL solved in benzene
      diffuses 2 orders of magnitude faster than the neat IL. Lastly, simulations show
      that CO2 molecules are absorbed in four different regions of the ILRM system,
      that is, (I) in the IL inner core, (II) in the [BHD](+) surfactant cation layer,
      (III) at the interface between the [BHD](+) surfactant cation layer and benzene
      solvent, and (IV) in the benzene solvent. The CO2 solubility was found to
      decrease in the order II > III ~ IV > I, while the CO2 diffusivity and
      permeability decrease in the following order: IV > III > II > I. 

PMID- 25382317
TI  - Multimodal and time-lapse skin registration.
AB  - BACKGROUND/PURPOSE: Computational skin analysis is revolutionizing modern
      dermatology. Patterns extracted from image sequences enable algorithmic
      evaluation. Stacking multiple images to analyze pattern variation implicitly
      assumes that the images are aligned per-pixel. However, breathing and involuntary
      motion of the patient causes significant misalignment. Alignment algorithms
      designed for multimodal and time-lapse skin images can solve this problem.
      Sequences from multi-modal imaging capture unique appearance features in each
      modality. Time-lapse image sequences capture skin appearance change over time.
      METHODS: Multimodal skin images have been acquired under five different
      modalities: three in reflectance (visible, parallel-polarized, and cross
      polarized) and two in fluorescence mode (UVA and blue light excitation). For time
      lapse imagery, 39 images of acne lesions over a 3-month period have been
      collected. The method detects micro-level features like pores, wrinkles, and
      other skin texture markings in the acquired images. Images are automatically
      registered to subpixel accuracy. RESULTS: The proposed registration approach
      precisely aligns multimodal and time-lapse images. Subsurface recovery from
      multimodal images has misregistration artefacts that can be eliminated using this
      approach. Registered time-lapse imaging captures the evolution of appearance of
      skin regions with time. CONCLUSION: Misalignment in skin imaging has significant
      impact on any quantitative or qualitative image evaluation. Micro-level features
      can be used to obtain highly accurate registration. Multimodal images can be
      organized with maximal overlap for successful registration. The resulting point
      to-point alignment improves the quality of skin image analysis.

PMID- 25382318
TI  - Pediatric syncope: where are we now?

PMID- 25382315
TI  - Neural function, injury, and stroke subtype predict treatment gains after stroke.
AB  - OBJECTIVE: This study was undertaken to better understand the high variability in
      response seen when treating human subjects with restorative therapies poststroke.
      Preclinical studies suggest that neural function, neural injury, and clinical
      status each influence treatment gains; therefore, the current study hypothesized
      that a multivariate approach incorporating these 3 measures would have the
      greatest predictive value. METHODS: Patients 3 to 6 months poststroke underwent a
      battery of assessments before receiving 3 weeks of standardized upper extremity
      robotic therapy. Candidate predictors included measures of brain injury
      (including to gray and white matter), neural function (cortical function and
      cortical connectivity), and clinical status (demographics/medical history,
      cognitive/mood, and impairment). RESULTS: Among all 29 patients, predictors of
      treatment gains identified measures of brain injury (smaller corticospinal tract
      [CST] injury), cortical function (greater ipsilesional motor cortex [M1]
      activation), and cortical connectivity (greater interhemispheric M1-M1
      connectivity). Multivariate modeling found that best prediction was achieved
      using both CST injury and M1-M1 connectivity (r(2) = 0.44, p = 0.002), a result
      confirmed using Lasso regression. A threshold was defined whereby no subject with
      >63% CST injury achieved clinically significant gains. Results differed according
      to stroke subtype; gains in patients with lacunar stroke were best predicted by a
      measure of intrahemispheric connectivity. INTERPRETATION: Response to a
      restorative therapy after stroke is best predicted by a model that includes
      measures of both neural injury and function. Neuroimaging measures were the best
      predictors and may have an ascendant role in clinical decision making for
      poststroke rehabilitation, which remains largely reliant on behavioral
      assessments. Results differed across stroke subtypes, suggesting the utility of
      lesion-specific strategies.

PMID- 25382319
TI  - Clinical features and management of postural tachycardia syndrome in children: a
      single-center experience.
AB  - BACKGROUND: The incidence of postural tachycardia syndrome (POTS) has been
      increasing in children and adolescents, while clinical characteristics of POTS in
      the pediatric population are not fully understood. METHODS: An observational
      study was performed in 150 pediatric patients aged between 5 and 18 years who
      underwent head-up tilt test (HUTT) with the diagnosis of POTS at Peking
      University First Hospital from March 2008 to August 2013. Demographic data,
      clinical presentation, autonomic parameters, laboratory findings, and treatments
      were recorded. RESULTS: POTS in children commonly occurred in the age of 7-14
      years. Dizziness (84.00%) was the most common symptom, followed by weakness
      (72.00%) and orthostatic syncope (62.67%). Positive family history of orthostatic
      intolerance (OI) was found in 24.64% of children with POTS. And 33.09% of them
      had preceding infection history as precipitating events. Ten percent of them
      suffered from orthostatic hypertension. Hyperadrenergic status was documented in
      51.28% of 39 patients who were tested for the standing norepinephrine levels.
      More than half of POTS patients, with 24-hour urinary sodium level <124 mmol/24
      hours, were suitable for treatment of salt supplementation. At least 25.74% of
      POTS patients were of positive acetylcholine receptor (AChR) antibody. Low iron
      storage in children with POTS was relatively rare. Most patients responded well
      to treatments, 43.51% of patients recovered, while 7.63% of them had relapse
      after symptoms disappeared. CONCLUSIONS: POTS is a relatively common condition
      with complex pathophysiology and heterogeneous clinical manifestation. A
      comprehensive therapeutic regimen is recommended for the treatment.

PMID- 25382320
TI  - Prognostic analysis of orthostatic intolerance using survival model in children.
AB  - BACKGROUND: Orthostatic intolerance (OI) is a common disease at pediatric period
      which has a serious impact on physical and mental health of children. The purpose
      of this study was to investigate the effect of related factors on the prognosis
      of children with OI. METHODS: The subjects were 170 children with OI, including
      71 males (41.8%) and 99 females (58.2%) with age from 6 to 17 (12.0+/-2.6) years.
      The effect of related factors on the prognosis of children was studied by using
      univariate analysis. Then, the impact of children's age, symptom score, duration,
      disease subtype, and treatment on patient's prognosis was studied via analysis of
      COX proportional conversion model. RESULTS: Among 170 cases, 48 were diagnosed
      with vasovagal syncope, including 28 cases of vasoinhibitory type, 16 cases of
      mixed type, and 4 cases of cardioinhibitory type; 115 cases were diagnosed with
      postural tachycardia syndrome and 7 cases with orthostatic hypotension. By using
      univariate analysis of Cox regression, the results showed that symptom score had
      a marked impact on the time of symptoms improvement of children after taking
      medication (P < 0.05), while other univariates had no impact (P > 0.05).
      Multivariate analysis using Cox proportional hazards regression model showed that
      the symptom score at diagnosis had a significant effect on holding time of
      symptoms improvement of children after taking medication (P < 0.05). Kaplan-Meier
      curve showed that symptom-free survival was higher in children with symptom score
      equal to 1 than children with symptom score equal to or greater than 2 during
      follow-up (P < 0.05). CONCLUSION: Symptom score is an important factor affecting
      the time of symptom improvement after treatment for children with OI.

PMID- 25382321
TI  - Immune regulation of hydrogen sulfide in children with acute lymphoblastic
      leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) and chemotherapy can cause immune
      imbalance, and gaseous molecule hydrogen sulfide (H2S) can participate in the
      process of immune response. This study aimed to investigate the immune regulation
      of H2S in pediatric ALL. METHODS: Children (n = 78) with ALL admitted during 2010
      2013 were included in this study. Two blood samples were collected in period of
      before chemotherapy, bone marrow remission and two days after chemotherapy,
      respectively. Serum contents of H2S and cytokines, including interleukin-1beta
      (IL-1beta), interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumor necrosis
      factor (TNF-alpha), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10
      (IL-10) and macrophage inflammatory protein-1alpha (MIP-1alpha), were detected
      using ELISA method. Stepwise regression was used to analyze the correlation
      between H2S and cytokines. Furthermore, human Jurkat cells were cultured in
      vitro, and nucleoprotein of Jurkat cells and peripheral blood mononuclear cells
      (PBMCs) were collected, contents of cystathionine gamma-lyase (CSE) and certain
      cytokines were measured by Western blotting. RESULTS: Serum concentrations of
      H2S, IL-1beta, IL-6, IL-10 and MIP-1a in children with ALL were increased
      significantly (P < 0.01), while concentrations of IL-2, TNF-alpha, IFN-gamma and
      IL-4 decreased obviously (P < 0.01). In patients after chemotherapy,
      concentrations of H2S and IL-10 were decreased significantly (P < 0.05), but IL-4
      and IFN-gamma concentrations increased markedly (P < 0.05). At remission stage,
      H2S, IL-1beta, IL-4, IL-6, IL-10 and MIP-1alpha concentrations were further
      decreased markedly (P < 0.05), but concentrations of IL-2, TNF-alpha and IFN
      gamma increased again (P < 0.05). Protein contents of CSE, IL-10, IL-4 and IL-2
      of PBMCs also increased markedly in children with ALL. Moreover, changes of CSE
      protein contents of PBMCs were consistent with serum H2S contents, and there were
      significant correlation between H2S and certain cytokines based on stepwise
      regression analysis. Furthermore, compared with those of PBMCs group, in vitro
      study indicated that Jurkat cells of H2S group expressed IFN-gamma, IL-10, IL-4
      and IL-2 protein increased obviously (P < 0.05), while IL-4, IL-2 and CSE
      expression of PPG group decreased markedly (P < 0.05). CONCLUSION: Gaseous
      molecule H2S might participate in the process of immune regulation in pediatric
      ALL through modulating transcription and expression of cytokines.

PMID- 25382322
TI  - Cardiovascular magnetic resonance imaging findings in children with myocarditis.
AB  - BACKGROUND: Myocarditis is a common, potentially life-threatening disease that
      presents a wide rang of symptoms in children, as an important underlying etiology
      of other myocardial diseases such as dilated and arrhythmogenic right ventricular
      cardiomyopathy. The incidence of nonfatal myocarditis is probably greater than
      that of the one actually diagnosed, which is the result of the challenges of
      establishing the diagnosis in standard clinical settings. Currently, no single
      clinical or imaging finding confirms the diagnosis of myocarditis with absolute
      certainty. Historically, clinical exam, electrocardiogram (ECG), serology and
      echocardiography had an unsatisfactory diagnostic accuracy in myocarditis.
      Endomyocardial biopsy remains as a widely accepted standard, but may not be
      suitable for every patient, especially for those with less severe disease. Our
      aim was to find the changes in cardiovascular magnetic resonance (CMR) imaging of
      children with myocarditis diagnosed by clinical criteria. METHODS: We studied 25
      children (18 male, 7 female; aged from 5-17 years) with diagnosed myocarditis by
      clinical criteria. CMR included function analyses, T2-weighted imaging, T1
      weighted imaging before and after i.v. gadolinium injection (early gadolinium
      enhancement (EGE) and late gadolinium enhancement (LGE)). RESULTS: The T2 ratio
      was elevated in 21 children (84%, 11 in anterolateral (44%), 5 in inferolateral
      (20%), and 5 in septum (20%)), EGE was present in 9 children (36%, 3 in
      anterolateral (12%), 4 in inferolateral (20%), and 2 in septum (8%)), and LGE was
      present in 5 children (20%, 2 in anterolateral (8%), 1 in inferolateral (4%), 1
      in septum (4%), and 1 in midwall of left ventricular (LV) wall). In 9 children
      (36%), two (or more) out of three sequences (T2, EGE, LGE) were abnormal.
      CONCLUSIONS: The CMR findings in children with clinically diagnosed myocarditis
      vary within the groups, including regional or global myocardial signal increase
      in T2-weighted images, EGE and LGE in T1-weighted images. The T2 ratio elevation
      is the most common CMR finding. Children with mild cardiac symptoms may also
      appear serious myocardial injuries.

PMID- 25382323
TI  - Virus profile in children with acute respiratory infections with various
      severities in Beijing, China.
AB  - BACKGROUND: Acute respiratory infection (ARI) is one of the most common
      infectious diseases in infants and young children globally. This study aimed to
      determine the virus profile in children with ARI presenting with different
      severities. METHODS: Clinical specimens collected from children with ARI in
      Beijing from September 2010 to March 2011 were investigated for 18 respiratory
      viruses using an xTAG Respiratory Viral Panel Fast (RVP Fast) assay. The Pearson
      chi-square analysis was used to identify statistical significance. RESULTS: Of
      270 cases from three groups of ARI patients, including Out-patients, In-patients
      and patients in the intensive care unit (ICU), viruses were detected in 176
      (65.2%) specimens with the RVP Fast assay. The viral detection rate from the Out
      patients group (50.0%) was significantly lower than that from the In-patients
      (71.1%) and ICU-patients (74.4%) groups. The virus distribution was different
      between the Out-patients group and the other hospitalized groups, while the virus
      detection rate and distribution characteristics were similar between the In
      patients and ICU-patients groups. The co-infection rates of the Out-patients
      group, the In-patients group, and the ICU-patients group were 15.6%, 50.0% and
      35.8%, respectively. In addition to respiratory syncytial virus (RSV) and
      adenovirus (ADV), human rhinovirus (HRV) was frequently detected from children
      with serious illnesses, followed by human metapneumovirus (hMPV), human bocavirus
      (HBoV) and coronaviruses. Parainfluenza virus 3 (PIV3) was detected in children
      with lower respiratory illness, but rarely from those with serious illnesses in
      the ICU-patient group. CONCLUSION: In addition to so-called common respiratory
      viruses, virus detection in children with ARI should include those thought to be
      uncommon respiratory viruses, especially when there are severe ARI-related
      clinical illnesses.

PMID- 25382324
TI  - Granulocyte colony-stimulating factor ameliorates coronary artery elastin
      breakdown in a mouse model of Kawasaki disease.
AB  - BACKGROUND: Coronary artery damage from Kawasaki disease (KD) is closely linked
      to the dysfunction of the endothelial progenitor cells (EPCs). The aim of the
      present study was to evaluate the modulatory effect of granulocyte colony
      stimulating factor (G-CSF) on EPCs and elastin breakdown of coronary arteries in
      a KD mouse model. METHODS: A Lactobacillus casei cell wall extract (LCWE)-induced
      KD model was established in C57BL/6 mice that were subsequently administrated
      with recombinant human G-CSF (rhG-CSF). Nomega-nitro-L-arginine methyl ester (L
      NAME) was administrated for the negative intervention. Evaluations included
      coronary artery lesions, EPC number and functions, and the plasma concentration
      of nitric oxide (NO). RESULTS: Elastin breakdown was found in the coronary
      arteries of model mice 56 days after injection of LCWE. The number of circulating
      EPCs, plasma concentration of NO, and functions of bone marrow EPCs, including
      proliferation, adhesion, and migration abilities, were all lower in the KD model
      group compared with those in the control group. After administration of rhG-CSF,
      the number of circulating EPCs and plasma concentration of NO were increased
      significantly compared with those in the KD model group. There were also
      increases in the functional indexes of EPCs. Furthermore, rhG-CSF administration
      improved the elastin breakdown effectively. However, these protective effects of
      rhG-CSF on coronary arteries were attenuated by L-NAME. CONCLUSION: The present
      study indicated that the administration of G-CSF prevents elastin breakdown of
      the coronary arteries by enhancing the number and functions of EPCs via the NO
      system, and then accelerates the repair of coronary artery lesions in the KD.

PMID- 25382325
TI  - Mizoribine versus mycophenolate mofetil or intravenous cyclophosphamide for
      induction treatment of active lupus nephritis.
AB  - BACKGROUND: Lupus nephritis (LN) is one of the most serious manifestations of
      systemic lupus erythematosus. Although there have been substantial improvements
      in LN treatment over the last decade, the outcome remains unoptimistic in a
      considerable percentage of patients. The aim of this study was to evaluate the
      efficacy and safety of mizoribine (MZR), a novel selective inhibitor of inosine
      monophosphate dehydrogenase, as induction treatment for active LN in comparison
      with mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC). METHODS:
      Ninety patients with active LN were observed. Thirty patients were given MZR
      orally at the dose of 300 mg every other day. Thirty patients took MMF at 2 g per
      day in two divided doses. Thirty patients received CYC intravenously 0.5 g every
      2 weeks. Therapeutic effects and adverse events (AEs) were evaluated at the end
      of 24-week treatment. One-way analysis of variance (ANOVA) followed by Dunn's
      test was applied to compare the difference among the groups. For comparing
      categorical data between two groups, chi(2) test was employed. RESULTS: Early
      responses at week 12 were achieved by 73.3%, 90.0%, and 96.7% in MZR, MMF, and
      CYC groups, respectively. There was no significant difference in the complete
      remission rates (22.7%, 24.0%, and 25.0%, respectively) or overall response rates
      (68.2%, 72.0%, and 75.0%, respectively) among the three groups at week 24. The
      most prominent drop-down of Systemic Lupus Erythematosus Disease Activity Index
      scores was observed in MMF or CYC group, and the decline of health assessment
      questionnaire scores in MZR or MMF group was more prominent than that in the CYC
      group at week 12. Serum complement 3 (C3) or C4 levels were elevated in all
      groups after the treatments. CYC was more effective in inhibiting anti-double
      stranded DNA antibody, while MZR was more effective in inhibiting antinuclear
      antibody. The incidences of AEs in patients treated with CYC were significantly
      higher than those in patients treated with MZR or MMF (24.2% for CYC vs. 3.3% for
      MZR, and 2.6% for MMF, P = 0.01). CONCLUSIONS: MZR is well tolerated and has an
      effect similar to MMF in the induction therapy of active LN. MZR may serve as an
      alternative approach for LN patients.

PMID- 25382326
TI  - Big bright black eyes.

PMID- 25382327
TI  - Two congenital coronary abnormalities affecting heart function: anomalous origin
      of the left coronary artery from the pulmonary artery and congenital left main
      coronary artery atresia.
AB  - BACKGROUND: The anomalous origin of the left coronary artery (LCA) from the
      pulmonary artery (ALCAPA) and congenital left main coronary artery atresia (CLMCA
      A) are two kinds of very rare coronary heart diseases which affect heart function
      profoundly. This study aimed to retrospectively illustrate the clinical features
      and therapy experience of ALCAPA and CLMCA-A patients. METHODS: From April 1984
      to July 2012, in Beijing Anzhen Hospital, 23 patients were diagnosed with ALCAPA
      and 4 patients with CLMCA-A. We summarized the clinical data of the 27 cases and
      retrospectively analyzed the clinical manifestation, diagnosis, and treatments of
      these two kinds of congenital coronary abnormalities. RESULTS: The 23 patients
      (13 males and 10 females, aged ranging from 2.5 months to 65 years) identified
      with ALCAPA were classified into infantile type (age of onset younger than 12
      months, 16 cases) and adult type (age of onset older than 12 months, 7 cases).
      Four patients were diagnosed with CLMCA-A (three males and one female, aged
      ranging from 3 months to 2 years). The main clinical manifestations of infantile
      type ALCAPA and CLMCA-A include repeated respiratory tract infection, heart
      failure, dyspnea, feeding intolerance, diaphoresis, and failure to thrive. And
      these two congenital coronary abnormalities might be misdiagnosed as endocardial
      fibroelastosis, dilated cardiomyopathy, and acute myocardial infarction. As for
      the adult-type ALCAPA, cardiac murmurs and discomfort of the precordial area are
      the most common presentations and might be misdiagnosed as coronary heart
      disease, myocarditis, or patent ductus arteriosus. In ECG examination: Infantile
      type ALCAPA and CLMCA-A showed abnormal Q waves with T wave inversion in leads I,
      avL, and V4-V6, especially in lead avL. However, ECG of adult-type ALCAPA lacked
      distinct features. In chest radiography: pulmonary congestion and cardiomegaly
      were the most common findings in infantile-type ALCAPA and CLMCA-A, while
      pulmonary artery segment dilation was more common in adult type. In
      echocardiography, the common features of infantile-type ALCAPA and CLMCA-A
      included left ventricular enlargement, left ventricular systolic function normal
      or mildly reduced in CLMCA-A or significantly reduced in ALCAPA, and moderate to
      large mitral valve. It was performed in 9 of 23 cases of ALCAPA and showed the
      origin of the dilated right coronary artery (RCA) from the right sinus of the
      aortic root and absence of LCA origin in angiography. After opacification of RCA,
      reverse flow in the LCA and pulmonary artery was visualized through coronary
      artery collateral circulation. Angio was performed in three of the four cases of
      CLMCA-A and showed left main coronary artery was a blind end, with diameter of
      only 1.1-2.0 mm. Treatment and prognosis: 21 patients with ALCAPA had cardiac
      surgery and 6 of them died postoperatively. Fifteen postoperative patients
      survived without overt symptoms within the follow-up period of 6-166 months
      (median 17 months). As for treatment of CLMCA-A, four patients took digoxin and
      diuretics without undergoing cardiac surgery. Their clinical symptoms improved
      during the close follow-ups. CONCLUSIONS: ALCAPA and CLMCA-A are two rare
      coronary artery abnormalities that affect cardiac function in infants and
      children. In younger patients with cardiomegaly and heart dysfunction these two
      congenital coronary diseases should be noticed.

PMID- 25382328
TI  - Effect of short-term high-dose atorvastatin on systemic inflammatory response and
      myocardial ischemic injury in patients with unstable angina pectoris undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) could develop periprocedural
      myocardial infarction and inflammatory response and statins can modify
      inflammatory responses property. The aim of this study was to evaluate whether
      short-term high-dose atorvastatin therapy can reduce inflammatory response and
      myocardial ischemic injury elicited by PCI. METHODS: From March 2012 to May 2014,
      one hundred and sixty-five statin-naive patients with unstable angina referred
      for PCI at Department of Cardiology of the 306th Hospital, were enrolled and
      randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group (HD
      group, n = 56) or 20 mg/d as normal dose group (ND group, n = 57) or an
      additional single high loading dose (80 mg) followed 6-day atorvastatin 20 mg/d
      as loading dose group (LD group, n = 52). Plasma C-reactive protein (CRP) and
      interleukin-6 (IL-6) levels were determined before intervention and at 5 minutes,
      24 hours, 48 hours, 72 hours, and 7 days after intervention. Creatine kinase
      myocardial isoenzyme (CK-MB) and cardiac troponin I (cTnI) were measured at
      baseline and then 24 hours following PCI. RESULTS: Plasma CRP and IL-6 levels
      increased from baseline after PCI in all groups. CRP reached a maximum at 48
      hours and IL-6 level reached a maximum at 24 hours after PCI. Plasma CRP levels
      at 24 hours after PCI were significantly lower in the HD group ((9.14+/-3.02)
      mg/L) than in the LD group ((11.06+/-3.06) mg/L) and ND group ((12.36+/-3.08)
      mg/L, P < 0.01); this effect persisted for 72 hours. IL-6 levels at 24 hours and
      48 hours showed a statistically significant decrease in the HD group ((16.19+/
      5.39) ng/L and (14.26+/-4.12) ng/L, respectively)) than in the LD group ((19.26+/
      6.34) ng/L and (16.03+/-4.08) ng/L, respectively, both P < 0.05) and ND group
      ((22.24+/-6.98) ng/L and (17.24+/-4.84) ng/L, respectively). IL-6 levels at 72
      hours and 7 days showed no statistically significant difference among the study
      groups. Although PCI caused a significant increase in CK-MB and cTnI at 24 hours
      after the procedure in all groups, the elevated CK-MB and cTnI values were lower
      in the HD group ((4.71+/-4.34) ng/ml and (0.086+/-0.081) ng/ml, respectively)
      than in the ND group ((7.24+/-6.03) ng/ml and (0.138+/-0.103) ng/ml,
      respectively, both P < 0.01) and LD group ((6.80+/-5.53) ng/ml and (0.126+/
      0.101) ng/ml, respectively, both P < 0.01). CONCLUSION: Short-term high-dose
      atorvastatin treatment before PCI significantly reduced systemic inflammatory
      response and myocardial ischemic injury elicited by PCI.

PMID- 25382329
TI  - Investigation of drugs responsible for perioperative anaphylactic reactions using
      cellular allergen stimulation test.
AB  - BACKGROUND: Anaphylactic reactions during anesthesia and operation are common and
      life threatening. Follow-up investigation is necessary for avoiding potential re
      exposure of the patients to the offending drugs. The purpose of this study was to
      assess cellular allergen stimulation test (CAST) as a diagnostic instrument in
      immunoglobulin E (IgE)- and non-IgE-mediated anaphylactic reactions. METHODS:
      This study included 25 patients who developed perioperative anaphylactic
      reactions and 10 subjects that tolerated anesthetics and other drugs during
      perioperative period from September 2009 to October 2013 in Peking Union Medical
      College Hospital. We performed skin tests and flow cytometric analysis of
      basophil activation-based CAST in all subjects. RESULTS: Of the 25 patients, 17
      had IgE-mediated anaphylactic reactions (causative agent identified by skin
      tests) and 8 had non-IgE-mediated anaphylactic reactions (negative skin tests).
      CAST showed a sensitivity of 42.9%, specificity of 90%, and negative predictive
      value of 80.6% for neuromuscular blocking agents. CONCLUSIONS: CAST may be useful
      for the diagnosis of anaphylactic reactions during perioperative period. Our
      findings call for further investigation to increase the sensitivity of the test.

PMID- 25382330
TI  - Evaluation of the Xpert MTB/RIF assay for diagnosis of tuberculosis and rifampin
      resistance in county-level laboratories in Hunan province, China.
AB  - BACKGROUND: The Xpert MTB/RIF showed high sensitivity and specificity in previous
      studies carried out in different epidemiological and geographical settings and
      patient populations in high-burden tuberculosis (TB) countries. However, there
      were little data obtained by validation or demonstration study of the assay in
      China. In this study, the performance of Xpert MTB/RIF was investigated in two
      county-level laboratories in Hunan Province, China. METHODS: Consecutive patients
      with suspected pulmonary tuberculosis (PTB) and suspicion for multidrug-resistant
      tuberculosis (MDR-TB) were enrolled. For each patient suspected to have PTB,
      three sputum specimens (one spot sputum, one night sputum, and one morning
      sputum) were collected and each sputum was tested with smear microscopy,
      Lowenstein-Jensen (LJ) culture, and Xpert MTB/RIF test. For comparison across
      subgroups and testing methods, 95% confidence intervals were calculated. All
      analyses were done with SPSS 16.0, and P < 0.05 was regarded as significant.
      RESULTS: For case detection, the sensitivity of Xpert MTB/RIF was 100% for smear-
      and culture-positive TB and 88.6% for smear-negative and culture-positive TB; the
      overall sensitivity was 94.5% for all culture-positive patients. The specificity
      was 99.8%. The sensitivity of Xpert MTB/RIF assay was 22.0% in clinical TB
      patients and the specificity reached 100.0% in the group of patients who are
      infected with nontuberculous mycobacteria. For the detection of rifampin
      resistance, the sensitivity of MTB/RIF RIF-resistance detection was 92.9%, and
      the specificity was 98.7%. Of the 26 Xpert MTB/RIF-positive and RIF-resistant
      patients confirmed by LJ proportion tests, 20 (76.9%) patients were infected by
      MDR-TB. CONCLUSIONS: The Xpert MTB/RIF assay is a highly sensitive and specific
      method for diagnosis of TB and RIF resistance, which will enable it to have the
      potential to be used in county-level laboratories and lead to the reduction of
      the infectious pool and improvements in TB control in China. Further evaluations
      in county-level laboratories for implementing the assay are still required.

PMID- 25382331
TI  - Hydrogen sulfide defends against the cardiovascular risk of Nw-nitro-L
      argininemethyl ester-induced hypertension in rats via the nitric
      oxide/endothelial nitric oxide synthase pathway.
AB  - BACKGROUND: Dyslipidemia caused by liver injury is a significant risk factor for
      cardiovascular complications. Previous studies have shown that hydrogen sulfide
      (H2S) protects against multiple cardiovascular disease states in a similar manner
      as nitric oxide (NO), and NO/endothelial nitric oxide synthase (eNOS) pathway is
      the key route of NO production. The purpose of this study was to investigate
      whether H2S can ameliorate the high blood pressure and plasma lipid profile in Nw
      nitro-L-argininemethyl ester (L-NAME)-induced hypertensive rats by NO/eNOS
      pathway. METHODS: Thirty-six 4-week old Sprague-Dawley (SD) male rats were
      randomly assigned to 6 groups (n = 6): control group, L-NAME group, control +
      glibenclamide group, control + NaHS group, L-NAME + NaHS group, and L-NAME + NaHS
      + glibenclamide group. Measurements were made of plasma triglycerides (TG), low
      density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol
      (CHO), glutamic-pyruvic transaminase (ALT) levels after 5 weeks. Then
      measurements of NO level and proteins expression of eNOS, P-eNOS, AKT, P-AKT were
      made in liver tissue. RESULTS: After 5 weeks of L-NAME treatment, the blood
      pressure, plasma TG ((1.22+/-0.12) mmol/L in L-NAME group vs. (0.68+/-0.09)
      mmol/L in control group; P < 0.05) and LDL ((0.54+/-0.04) mmol/L in L-NAME group
      vs. (0.28+/-0.02) mmol/L in control group; P < 0.05) concentration were
      significantly increased, and the plasma HDL ((0.26+/-0.02) mmol/L in L-NAME group
      vs. (0.69+/-0.07) mmol/L in control group; P < 0.05) concentration significantly
      decreased. Meanwhile the rats treated with L-NAME exhibit dysfunctional eNOS,
      diminished NO levels ((1.36+/-0.09) mmol/g protein in L-NAME group vs. (2.34+/
      0.06) mmol/g protein in control group; P < 0.05) and pathological changes of the
      liver. H2S therapy can markedly decrease the blood pressure ((37.25+/-4.46) mmHg
      at the fifth week; P < 0.05), and ameliorate the plasma TG ((0.59+/-0.06) mmHg),
      LDL ((0.32+/-0.04) mmHg), and HDL ((0.46+/-0.03) mmHg) concentration in L-NAME +
      NaHS group (all P < 0.05). H2S therapy can also restore eNOS function and NO
      bioavailability and attenuate the pathological changes in the liver in L-NAME
      induced hypertensive rats. CONCLUSION: H2S protects the L-NAME-induced
      hypertensive rats against liver injury via NO/ eNOS pathway, therefore decreases
      the cardiovascular risk.

PMID- 25382332
TI  - Oenanthe javanica extract increases immunoreactivities of antioxidant enzymes in
      the rat kidney.
AB  - BACKGROUND: Oenanthe javanica is an aquatic perennial herb originated from East
      Asia. Nowadays, the effects of Oenanthe javanica have been proven in various
      disease models. Studies regarding the antioxidant effect of Oenanthe javanica in
      the kidney are still unclear. METHODS: This study was therefore performed to
      investigate the effect of the Oenanthe javanica extract (OJE) in the rat kidney
      using immunohistochemistry for antioxidant enzymes, copper, zinc-superoxide
      dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT) and
      glutathione peroxidase (GPx). Sprague-Dawley rats were randomly assigned to three
      groups: (1) normal diet fed-group (normal-group), (2) diet containing ascorbic
      acid (AA)-fed group (AA-group) as a positive control, (3) diet containing OJE-fed
      group (OJE-group). AA and OJE were supplied during 28 days. RESULTS: The side
      effects were not observed in all the groups. Immunoreactivities of SOD1, SOD2,
      CAT and GPx were easily detected in the distal tubules of the kidney, and their
      immunoreactivities in the AA-and OJE-groups were increased to about 1.4-1.5 times
      and 2 times, respectively, compared with those in the normal-group. CONCLUSION:
      OJE significantly increased expressions of SOD1 & 2, CAT and GPx
      immunoreactivities in the distal tubules of the rat kidney, and this finding
      suggests that significant enhancements of endogenous enzymatic antioxidants by
      OJE treatment may be a legitimate strategy for decreasing oxidative stresses in
      the kidney.

PMID- 25382333
TI  - Effect of the disruption of three cytoskeleton components on chondrocyte
      metabolism in rabbit knee cartilage.
AB  - BACKGROUND: Chondrocytes' phenotype and biosynthesis of matrix are dependent on
      having an intact cytoskeletal structure. Microfilaments, microtubules, and
      intermediate filaments are three important components of the cytoskeletal
      structure of chondrocytes. The aims of this study were to determine and compare
      the effects of the disruption of these three cytoskeletal elements on the
      apoptosis and matrix synthesis by rabbit knee chondrocytes in vitro. METHODS:
      Chondrocytes were isolated from full-thickness knee cartilage of two-month-old
      rabbits using enzymatic methods (n = 24). The isolated cells were stabilized for
      three days and then exposed to low, medium, and high doses of chemical agents
      that disrupt the three principal cytoskeletal elements of interest: colchicine
      for microtubules, acrylamide for intermediate filaments, and cytochalasin D for
      actin microfilaments. A group of control cells were treated with carrier. Early
      apoptosis was assessed using the Annexin-FITC binding assay by flow cytometry on
      days 1 and 2 after exposure to the disrupting chemical agents. The components and
      distribution of the cytoskeleton within the cells were analyzed by laser scanning
      confocal microscopy (LSCM) with immunofluorescence staining on day 3. The mRNA
      levels of aggrecan (AGG) and type II collagen (Col-2) and their levels in culture
      medium were analyzed using real-time PCR and enzyme-linked immunosorbent
      serologic assay (ELISA) on days 3, 6, and 9. RESULTS: In the initial drug-dose
      response study, there was no significant difference in the vitality of cells
      treated with 0.1 umol/L colchicine, 2.5 mmol/L acrylamide, and 10 ug/L
      cytochalasin D for two days when compared with the control group of cells. The
      concentrations of colchicine and acrylamide treatment selected above
      significantly decreased the number of viable cells over the nine-day culture and
      disrupted significantly more cell nuclei. Real-time PCR and ELISA results showed
      that the mRNA levels and medium concentrations of AGG and Col-2 were
      significantly decreased for cultures treated with colchicine and acrylamide when
      compared with untreated cells at three, six, and nine days, and this inhibition
      was correlated with higher matrix metalloprotease-13 expression in these cells.
      Cellular proliferation, monolayer morphology, and matrix metabolism were
      unaffected in cytochalasin D-treated cells when compared with control cells over
      the nine-day culture period. CONCLUSIONS: The disruption of the microtubulin and
      intermediate filaments induced chondrocyte apoptosis, increased matrix
      metalloprotease expression, and decreased AGG and Col-2 expression in rabbit knee
      chondrocyte cultures. Our findings suggest that microtubulin and intermediate
      filaments play a critical role in the synthesis of cartilage matrix by rabbit
      knee chondrocytes.

PMID- 25382334
TI  - Expression and significance of fat mass and obesity associated gene and forkhead
      transcription factor O1 in non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex disorder and
      has been closely linked to obesity. The fat mass and obesity-associated (FTO)
      gene is a newly discovered gene related to obesity, which enhances oxidative
      stress and lipogenesis in NAFLD. The forkhead transcription factor O1 (FoxO1) is
      another important gene involved in NAFLD, which causes lipid disorders when
      insulin resistance appears in the liver. However, the interactions between FTO
      and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated. This
      study was designed to identify the relationship between these two factors that
      are involved in the development of NAFLD. METHODS: This study includes two parts
      referred to as animal and cell experiments. Twelve female SPF C57BL/6 mice were
      fed a high-fat diet to serve as an NAFLD animal model. Aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), total triglyceride (TG), total cholesterol
      (TC), alkaline phosphatase (ALP), high-density lipoprotein (HDL), and low-density
      lipoprotein (LDL) were measured. Immunohistochemical analysis was used to detect
      the expression and histological localization of FTO, FoxO1, and adenosine
      monophosphate (AMP)-activated protein kinase (AMPK). The L02 cells were exposed
      to high fat for 24, 48, or 72 hours. Oil red O staining was used to detect
      intracellular lipid droplets. Reverse transcription-polymerase chain reaction was
      used for analyzing the levels of FTO and FoxO1 mRNA. RESULTS: At the end of 10
      weeks, ALP, ALT, AST, and LDL were significantly increased (P < 0.01), while TC
      and TG were also significantly higher (P < 0.05). In addition, HDL was
      significantly decreased (P < 0.05). The FTO and FoxO1 proteins were weakly
      expressed in the control group, but both FTO and FoxO1 were expressed
      significantly higher (P < 0.01) in the experimental group, and the expression of
      the two factors was significantly correlated. AMPK in the high-fat group showed a
      low level of correlation with FTO, but not with FoxO1. Oil Red O staining results
      showed that the cells cultured in 50% fetal bovine serum for 24, 48, or 72 hours
      exhibited steatosis. FTO and FoxO1 mRNA were increased in the high-fat group
      compared with the normal group (P < 0.01). The expression levels of FTO and FoxO1
      mRNA were the highest at 48 hours (P < 0.05). CONCLUSIONS: A high-fat diet leads
      to higher expression of FTO, phosphorylation of FoxO1, and decreased
      phosphorylation of AMPK. These results suggest that the interactions between FTO
      and FoxO1 are closely related to the pathogenesis of NAFLD.

PMID- 25382335
TI  - Cytotoxic effects of sodium dodecyl benzene sulfonate on human keratinocytes are
      not associated with proinflammatory cytokines expression.
AB  - BACKGROUND: Keratinocytes play a crucial role in the biological function of skin
      barrier. The relationship between sodium lauryl sulfate (SLS) and keratinocytes
      has been studied. However, the cytotoxicity and effects of sodium dodecyl benzene
      sulfonate (SDBS), a common detergent similar to SLS, on keratinocytes are still
      not known. This study aimed to investigate the effects of SDBS on cytotoxicity
      and expression of proinflammatory cytokines in cultured human keratinocytes.
      METHODS: This study was carried out using the keratinocytes cell line, HaCaT
      cells. The cytotoxicity of SDBS on HaCaT cells was evaluated with cell counting
      kit-8 (CCK-8) and phase-contrast microscopy. After exposure to different
      concentrations of SDBS, the total RNA of the HaCaT cells was extracted for
      evaluating the relative mRNA expression of IL-1alpha, IL-6, IL-8, and TNF-alpha
      by qPCR. The supernatants of cells were collected for measuring the levels of IL
      6 and IL-8 by enzyme-linked immunosorbent assay (ELISA). RESULTS: SDBS at
      concentrations of 20 ug/ml and over showed direct cytotoxicity and induced
      morphological changes of the HaCaT cells. The mRNA expressions of IL-1alpha, IL
      6, IL-8, and TNF-a in different concentrations of SDBS at different time were
      comparable with that of controls. SDBS at concentrations of 5, 10, and 15 ug/ml
      had no significant effects on IL-6 and IL-8 excretion from HaCaT cells after 24
      hour exposure. Moreover, no significant effects on the IL-6 and IL-8 excretion
      were found after 10 and 15 ug/ml SDBS stimulations for 6, 12, and 24 hours,
      respectively. CONCLUSION: SDBS at higher concentrations had cytotoxicity on HaCaT
      cells but had no effects on the mRNA expression of IL-1alpha, IL-6, IL-8, and TNF
      a, that was different from SLS.

PMID- 25382336
TI  - Association between interferon gamma receptor 1-56C/T gene polymorphism and
      tuberculosis susceptibility: a meta-analysis.
AB  - BACKGROUND: Genetic variations in the interferon-gamma (IFN-gamma) receptor 1
      gene (IFNGR1) may contribute to tuberculosis (TB) risk in different populations.
      Many studies have investigated the relationship between IFNGR1 56C/T polymorphism
      and the susceptibility to TB, but have yielded conflicting results. A
      comprehensive meta-analysis is needed to provide a more accurate estimation of
      the relationship between them. METHODS: A literature search based on a
      combination of manual and computer-based methods was conducted on four English
      databases (PubMed, Science Direct, SpringerLink, and EBSCO) and three Chinese
      databases (Wanfang, CQVIP, and Chinese National Knowledge Infrastructure
      databases). Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were
      calculated using either the fixed-effects model or the random-effects model for
      different genetic models based on the heterogeneity examination. RESULTS: A total
      of six studies comprising 1 497 confirmed TB cases and 1 802 controls were
      included in this meta-analysis. Overall, no significant association was observed
      between IFNGR1 -56C/T polymorphism and TB susceptibility (C vs. T, OR = 0.90, 95%
      CI 0.69-1.17; CC vs. TT, OR = 0.87, 95% CI 0.65-1.18; TC vs. TT, OR = 1.031, 95%
      CI 0.872-1.219; CC+TC vs. TT, OR = 0.89, 95% CI 0.64-1.26; CC vs. TC+TT, OR =
      0.92, 95% CI 0.66-1.29). In subgroup analysis, a significant association was
      found in the dominant model (CC+TC vs. TT, OR = 1.24, 95% CI 1.02-1.51) in
      Africans, but not in Asians or Caucasians. CONCLUSIONS: Our meta-analysis did not
      provide enough powerful evidence to identify a significant association between
      IFNGR1 -56C/T polymorphism and TB susceptibility in the overall population. In
      subgroup analysis, it indicates that IFNGR1 -56C/T is possibly associated with
      increased TB risk in Africans, but not in Asians or Caucasians. However, larger
      sample size and better-designed case-control studies are needed to validate these
      findings.

PMID- 25382337
TI  - Echocardiographic evaluation of right ventricular function in congenital heart
      disease.
AB  - OBJECTIVE: This review aims to provide an overview of conventional and novel
      indices used in clinical and research arenas for evaluation of right ventricular
      (RV) function in congenital heart diseases with a dual-chambered circulation.
      DATA SOURCES: Articles cited in this review were selected using PubMed search of
      publications in English with no date limits. The search terms included
      "echocardiography", "right ventricle", "RV function", "cardiac function", and
      "congenital heart disease". Key references were also searched for additional
      publications. STUDY SELECTION: Articles related to description of
      echocardiographic techniques in the evaluation of subpulmonary or systemic RV
      function and their applications in congenital cardiac malformations were
      retrieved and reviewed. RESULTS: Three approaches have been used to evaluate
      subpulmonary and systemic RV function: (1) assessment of changes in RV size in
      the cardiac cycle, (2) determination of Doppler-derived velocities and systolic
      and diastolic time intervals, and (3) quantification of myocardial velocities and
      deformation. CONCLUSIONS: Conventional and novel echocardiographic techniques
      enable the evaluation of subpulmonary and systemic RV function. Novel
      echocardiographic techniques have further allowed quantification of RV volumes
      and direct interrogation of myocardial deformation. These new techniques show
      promise in a more comprehensive evaluation beyond "eye-balling" of RV function in
      the growing population of adolescent and adult congenital heart patients.

PMID- 25382338
TI  - Prognostic markers for idiopathic pulmonary arterial hypertension.
AB  - OBJECTIVE: The objective of this study is to review the research on the
      prognostic markers of idiopathic pulmonary arterial hypertension (IPAH). DATE
      SOURCES: We searched literature from PubMed and CNKI databases both in English
      and Chinese up to 2013. STUDY SELECTION: Data about mortality and cut-off value
      are from clinical trials and identified by analysis. RESULTS: IPAH is an
      unexplained, progressive, and rare disease characterized by increased pulmonary
      artery pressure and pulmonary vascular resistance. The diagnosis is difficult,
      mortality of IPAH is high, and the survival periods are only 2-3 years after
      diagnosis. Investigations in recent years have identified a range of prognostic
      markers for IPAH, including the 6-minute walking test, red blood cell
      distribution width, and platelet levels, as well as imaging findings. Changes in
      these markers are important sources of information to predict the prognosis of
      patients with IPAH, which carries significant benefits for treatment planning.
      CONCLUSION: Even though the prognosis of IPAH has been investigated, the
      mortality is also high. More accurate and meaningful assessment for the prognosis
      of IPAH is required.

PMID- 25382339
TI  - Advances in the study on endogenous sulfur dioxide in the cardiovascular system.
AB  - OBJECTIVE: This review summarized the current advances in understanding the role
      of the novel gasotransmitter, sulfur dioxide (SO2), in the cardiovascular system.
      DATA SOURCES: Articles on the advances in the study of the role of endogenous
      sulfur dioxide in the cardiovascular system were accessed from PubMed and CNKI
      from 2003 to 2013, using keywords such as "endogenous sulfur dioxide" and
      "cardiovascular system". STUDY SELECTION: Articles with regard to the role of SO2
      in the regulation of cardiovascular system were selected. RESULTS: Recently,
      scientists discovered that an endogenous SO2 pathway is present in the
      cardiovascular system and exerts physiologically significant effects, such as
      regulation of the cardiac function and the pathogenesis of various
      cardiopulmonary diseases such as hypoxic pulmonary hypertension, hypertension,
      coronary atherosclerosis, and cardiac ischemia-reperfusion (I/R) injury, in the
      cardiovascular system. CONCLUSIONS: Endogenous SO2 is a novel member of the
      gasotransmitter family in addition to the nitric oxide (NO), carbon monoxide
      (CO), and hydrogen sulfide (H2S). Studies indicated that it has a role in
      regulating the cardiovascular disease.

PMID- 25382340
TI  - Lumbar pedicle cortical bone trajectory screw.
AB  - OBJECTIVE: The purpose of this study was to demonstrate the lumbar pedicle
      cortical bone trajectory (CBT) screw fixation technique, a new fixation technique
      for lumbar surgery. DATA SOURCES: The data analyzed in this review are mainly
      from articles reported in PubMed published from 1994 to 2014. STUDY SELECTION:
      Original articles and critical reviews relevant to CBT technique and lumbar
      pedicle fixation were selected. RESULTS: CBT technique was firstly introduced as
      a new fixation method for lumbar pedicle surgery in 2009. The concepts,
      morphometric study, biomechanical characteristics and clinical applications of
      CBT technique were reviewed. The insertional point of CBT screw is located at the
      lateral point of the pars interarticularis, and its trajectory follows a
      caudocephalad path sagittally and a laterally directed path in the transverse
      plane. CBT technique can be used for posterior fixation during lumbar fusion
      procedures. This technique is a minimally invasive surgery, which affords better
      biomechanical stability, fixation strength and surgical safety. Therefore, CBT
      technique has the greatest benefit in lumbar pedicle surgery for patients with
      osteoporosis and obesity. CONCLUSION: CBT technique is a better alternative
      option of lumbar pedicle fixation, especially for patients with osteoporosis and
      obesity.

PMID- 25382341
TI  - Application of stent implantation in congenital heart disease.

PMID- 25382342
TI  - Clinical progress of orthostatic hypertension in children.

PMID- 25382343
TI  - Bias in multiple-treatments meta-analysis: a case on comparative efficacy and
      tolerability of 15 antipsychotic drugs for schizophrenia.

PMID- 25382344
TI  - Cochlear implantation surgery in patients with totally ossified cochlea.

PMID- 25382345
TI  - Vindesine induces rhabdomyolysis in patients with acute lymphoblastic leukemia.

PMID- 25382346
TI  - Massive hemoptysis after a bronchoscopic biopsy in patients with endobronchial
      tuberculosis.

PMID- 25382347
TI  - A case of lethal hemolytic anemia associated with severe pneumonia caused by
      Mycoplasma pneumoniae.

PMID- 25382348
TI  - Propofol terminates ventricular fibrillation storm caused by pulmonary embolism.

PMID- 25382349
TI  - Pressure-induced metallization of dense (H2S)2H2 with high-Tc superconductivity.
AB  - The high pressure structures, metallization, and superconductivity of recently
      synthesized H2-containing compounds (H2S)2H2 are elucidated by ab initio
      calculations. The ordered crystal structure with P1 symmetry is determined,
      supported by the good agreement between theoretical and experimental X-ray
      diffraction data, equation of states, and Raman spectra. The Cccm structure is
      favorable with partial hydrogen bond symmetrization above 37 GPa. Upon further
      compression, H2 molecules disappear and two intriguing metallic structures with
      R3m and Im-3m symmetries are reconstructive above 111 and 180 GPa, respectively.
      The predicted metallization pressure is 111 GPa, which is approximately one-third
      of the currently suggested metallization pressure of bulk molecular hydrogen.
      Application of the Allen-Dynes-modified McMillan equation for the Im-3m structure
      yields high Tc values of 191 K to 204 K at 200 GPa, which is among the highest
      values reported for H2-rich van der Waals compounds and MH3 type hydride thus
      far.

PMID- 25382350
TI  - Improving hospital-based quality of care by reducing HIV-related stigma:
      evaluation results from Vietnam.
AB  - Operations Research conducted at four hospitals in Vietnam sought to reduce HIV
      related stigma and discrimination among hospital workers. The quasi-experimental
      study compared effects of focusing on 'fear-based' stigma (stemming from lack of
      knowledge) versus both fear-based and social stigma (stemming from moral
      judgments). Interventions included staff training (ranging from physicians to
      ward cleaners), hospital policy development, and supplies provision. At baseline
      (n = 795), reported stigma was substantial (e.g., about half of hospital workers
      indicated fear of casually touching PLHIV, and felt HIV was a punishment for bad
      behavior). By endline, stigma measures had improved significantly for both
      intervention groups (e.g., proportion reporting signs on beds indicating HIV
      status decreased from 51 to 24 % in Arm 1, and 31 to 7 % in Arm 2), with the
      combined intervention group showing greater effects. This study highlights
      successful strategies to reduce stigma, and thus, improve quality of care for
      PLHIV. 

PMID- 25382351
TI  - The impact of intensive multifactorial treatment on perceptions of chronic care
      among individuals with screen-detected diabetes: results from the ADDITION
      Denmark trial.
AB  - OBJECTIVES: To describe perceptions of chronic care among diabetes patients 6
      years after diagnosis by screening and to examine the impact of intensive
      treatment on patients' perceptions of chronic care. METHODS: The ADDITION-Denmark
      (2001-2006) trial compared the effects of intensive multifactorial therapy (IT)
      with routine care (RC) among individuals with screen-detected diabetes.
      Perceptions of chronic care were assessed using the Patient Assessment of Chronic
      Illness Care (PACIC) measure after 6-year follow-up (n = 937). Analysis was by
      intention-to-treat, accounting for clustering by general practice. RESULTS: The
      mean (SD) summary PACIC score was 2.4 (0.79) in the RC and 2.4 (0.82) in the IT
      group. The highest mean (SD) PACIC subscale score was for Delivery System
      Design/Decision Support [RC: 3.2 (0.95), IT: 3.3 (0.91)] and the lowest was for
      Follow-up/Coordination [RC: 2.1 (0.84), IT: 2.1 (0.87)]. Perceptions of chronic
      care did not differ between trial groups. CONCLUSIONS: Compared to RC, an
      intensive multifactorial intervention was not associated with differences in
      perceptions of chronic care among patients with screen-detected diabetes after 6
      years. Intensive treatment does not adversely affect perceptions of chronic care
      early in the course of the disease. However, there is potentially room for
      improvement in some aspects of chronic care.

PMID- 25382352
TI  - The psychological disengagement model among women in science, engineering, and
      technology.
AB  - Psychological responses to personal relative deprivation based on self/outgroup
      comparisons (named self/outgroup PRD) were explored among women in science,
      engineering, and technology according to the Psychological Disengagement Model.
      Three studies revealed that the experience of self/outgroup PRD increased women's
      likelihood of discounting the feedback they received at work. In turn,
      discounting led them to devalue their profession. Each study further documented
      the damaging effect of both psychological disengagement mechanisms. Study 1 (N =
      93) revealed that discounting and devaluing were associated with decreased self
      esteem. These results were replicated in Studies 2 and 3. Study 2 (N = 163)
      demonstrated that discounting and devaluing were also associated with reduced
      self-esteem stability. Study 3 (N = 187) further showed that psychological
      disengagement was also associated with women's occupational commitment.
      Theoretical and practical implications of these results are considered. 

PMID- 25382353
TI  - Low serum adiponectin levels are associated with reduced insulin sensitivity and
      lipid disturbances in short children born small for gestational age.
AB  - BACKGROUND: Being born as small for gestational age (SGA) has an increased risk
      of developing metabolic/cardiovascular disturbances in later life. The role of
      adiponectin in the metabolic disturbance in SGA children remained undefined.
      OBJECTIVE: The aim of this study was to investigate the association between serum
      levels of adiponectin and insulin sensitivity as well as lipid profile in short
      children born SGA at prepubertal ages. PATIENTS AND METHODS: Serum levels of
      adiponectin, fasting glucose, insulin, IGF-I, IGFBP-1, total cholesterol (TC),
      high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol
      (LDL-C), triglycerides (TG), apolipoprotein A-I (ApoA-I) and Apo B were measured
      in 30 prepubertal short children born SGA. Insulin resistance (IR) and beta-cell
      function were assessed using the method of homeostatic model (HOMA). Data were
      compared to those of 30 short appropriate for gestational age (AGA) children
      matched for age, gender, height and body mass index, and correlation analysis was
      performed. RESULTS: Short SGA children had significantly higher levels of fasting
      insulin, HOMA-IR and HOMA-beta but lower levels of adiponectin than short AGA
      controls. No significant differences in the level of IGFBP-1 and IGF-I were found
      between the two groups. Serum levels of TC, TG, Apo B and Apo B/ApoA-I ratio were
      significantly higher in SGA, with 33% of hypercholesteraemia and 23% of
      hyperglyceridaemia. Stepwise multiple regression analysis revealed that serum
      adiponectin level was negatively correlated with HOMA-IR and TG and was
      positively correlated with birthweight SDS in SGA children. CONCLUSIONS: These
      findings suggest that low serum adiponectin levels are associated with reduced
      insulin sensitivity and unfavourable lipid profiles in short children born SGA at
      prepubertal ages.

PMID- 25382354
TI  - No association between Annexin A5 genetic variants and deep venous thrombosis.

PMID- 25382355
TI  - Reducing Prescriptions of Long-Acting Benzodiazepine Drugs in Denmark: A
      Descriptive Analysis of Nationwide Prescriptions during a 10-Year Period.
AB  - Prolonged consumption of benzodiazepine drugs (BZD) and benzodiazepine receptor
      agonists (zolpidem, zaleplon, zopiclone; altogether Z drugs) is related to
      potential physiological and psychological dependence along with other adverse
      effects. This study aimed to analyse the prescribing of long-acting BZD (half
      life >10 hr), compared to short-acting BZD in Denmark during a 10-year period.
      Descriptive analysis of total sales data from the Danish Register of Medicinal
      Product Statistics, to individuals in the primary healthcare sector, of all BZD
      and Z drugs in the period of 2003-2013. Prescription data derive from all
      community and hospital pharmacies in Denmark. The prescribing of long-acting BZD
      was reduced from 25.8 defined daily doses (DDD)/1000 inhabitants/day in 2003 to
      8.8 DDD/1000 inhabitants/day in 2013, a relative reduction of 66%. The
      prescribing of short-acting BZD was reduced from 26.1 DDD/1000 inhabitants/day in
      2003 to 16.4 DDD/1000 inhabitants/day in 2013, a relative reduction of 37%.
      Prescription data in this study did not include information about indications for
      initiating treatments. In addition, due to compliance problems, some of the
      prescribed drugs may not have been consumed according to the prescription. The
      observed reduction in BZD use was correlated to the introduction of new national
      guidelines on prescription of addictive drugs, but this study was not designed to
      detect a causal relationship. The prescribing of long-acting BZD decreased
      considerably more than the prescribing of short-acting BZD in the 10-year period.

PMID- 25382356
TI  - Fruit and vegetable intake and rate of heart failure: a population-based
      prospective cohort of women.
AB  - AIMS: Although numerous studies have investigated fruit and vegetable consumption
      in association with cardiovascular diseases (CVD) such as coronary heart disease
      and stroke, a limited number of studies have investigated the association with
      heart failure. The aim of this study was to assess the association between fruit
      and vegetable intake and the incidence of heart failure among women. METHODS AND
      RESULTS: In September 1997, a total of 34,319 women (aged 49-83 years) from the
      Swedish Mammography Cohort, free of cancer and CVD at baseline, completed a food
      frequency questionnaire. Women were followed for incident heart failure
      (diagnosis as primary or secondary cause) through December 2011 using
      administrative health registries. Over 12.9 years of follow-up (442,348 person
      years), we identified 3051 incident cases of heart failure. Total fruit and
      vegetable consumption was inversely associated with the rate of heart failure
      {the multivariable-adjusted rate ratio (RR) in the highest quintile compared with
      the lowest was 0.80 [95% confidence interval (CI) 0.70-0.90]}. Fruit (mutually
      adjusted for vegetables) were not significantly associated with rate of heart
      failure (RR 0.94; 95% CI 0.83-1.07), whereas vegetables showed an inverse
      association (RR 0.83; 95% CI 0.73-0.95). When investigating the shape of
      association, we found evidence of a non-linear association (P = 0.01), and the
      lowest rates of heart failure were observed among women consuming >=5
      servings/day of fruit and vegetables, without further decrease with increasing
      intake. CONCLUSIONS: In this population-based prospective cohort study of women,
      higher total consumption of fruit and vegetables was inversely associated with
      the incidence of heart failure.

PMID- 25382357
TI  - A highly efficient and eco-friendly method for the synthesis of 1,3-indandione
      ring-fused 3-oxindoles bearing two contiguous quaternary stereocenters via an
      aldol reaction in aqueous media.
AB  - A highly efficient and environmentally benign method for the synthesis of
      oxindoles featuring two contiguous quaternary carbon centers via an aldol
      reaction starting from various 3-substituted oxindoles has been established. A
      wide variety of such featured multi-substituted 1,3-indandione ring-fused 3
      oxindole scaffolds were obtained smoothly in good yields (up to 98%) employing
      the most green of solvents, namely water, as reaction medium. Furthermore, their
      biological activity has been preliminarily demonstrated by in vitro evaluation
      against human prostate cancer cells PC-3, human lung cancer cells A549 and human
      leukemia cells K562 by MTT-based assays, using the commercially available
      standard drug, cisplatin, as a positive control. Gratifyingly, compounds 3s, 3u,
      3y and 3c' exhibited the best levels of in vitro inhibitory activity against
      human leukemia cells K562, which were almost 2.0, 2.8, 2.5 and 2.2 times,
      respectively, the activity of the positive control, cisplatin. Compound 3y had
      2.7 times the activity of the positive control, cisplatin, against PC-3 cancer
      cells, and 3s, 3u and 3c' showed levels of in vitro inhibitory activity against
      PC-3 cancer cells that were comparable to that of cisplatin. Compounds 3s, 3u and
      3y had good inhibitory ability against human lung cancer cells A549. The results
      indicated that 1,3-indandione ring-fused 3-oxindole analogs may be useful leads
      for further biological screenings. 

PMID- 25382358
TI  - Synthesis of Ag-In-Zn-S alloyed nanorods and their biological application.
AB  - Monodisperse Ag-In-Zn-S (AIZS) nanorods with a length of 20 nm have been
      synthesized using a facile solution based route. These nanorods showed a wide
      range of fluorescence emissions from green to red, which was achieved by
      controlling the chemical composition. Moreover, the obtained AIZS nanorods showed
      high-quality photoluminescence, as well as attractive two-photon fluorescence
      properties, indicating their potential capability in biological tagging upon near
      infrared excitation for deep tissue imaging. Furthermore, the AIZS nanorods
      presented in this report also show a promising perspective in applications such
      as solar cells and photocatalysts. 

PMID- 25382359
TI  - Post-traumatic stress symptoms and structure among orphan and vulnerable children
      and adolescents in Zambia.
AB  - BACKGROUND: Scant information exists on PTSD symptoms and structure in youth from
      developing countries. METHODS: We describe the symptom profile and exposure to
      trauma experiences among 343 orphan and vulnerable children and adolescents from
      Zambia. We distinguished profiles of post-traumatic stress symptoms using latent
      class analysis. RESULTS: Average number of trauma-related symptoms (21.6; range 0
      38) was similar across sex and age. Latent class model suggested 3 classes
      varying by level of severity: low (31% of the sample), medium (45% of the
      sample), and high (24% of the sample) symptomatology. CONCLUSIONS: Results
      suggest that PTSD is a continuously distributed latent trait.

PMID- 25382360
TI  - Unicompartmental knee arthroplasty: function versus survivorship, do we have a
      clue?

PMID- 25382361
TI  - In vivo kinematics of medial unicompartmental osteoarthritic knees during
      activities of daily living.
AB  - Few studies exist describing unicompartmental osteoarthritic knee kinematics.
      Moreover, the role of the anterior cruciate ligament (ACL) in the determination
      of knee kinematics has not been fully described. The objective of the current
      study was to analyze the in vivo kinematics of knees with medial osteoarthritis
      (OA) and intact ACL during closed and open chained motion. Eight patients
      scheduled for UKA diagnosed with primary medial OA underwent knee CT-scans and
      video-fluoroscopy. Fluoroscopic analysis included stair climbing, chair rising
      and leg extension. Three-dimensional bone positions were obtained from each image
      by iterative procedures using a CAD-model-based shape-matching technique.
      Patterns of axial rotation and anterior-posterior (AP) motion of the medial and
      lateral femoral condyle were obtained with specific software. The femur reported
      an overall external rotation relative to the tibia from extension to flexion in
      all tasks. Average AP translation of the medial femoral condyle were smaller in
      open-chained tasks than in weight-bearing conditions. Average AP motion of the
      lateral femoral condyle reported an overall posterior translation with knee
      flexion. The absent natural "screw-home" mechanism and the lack of medial condyle
      posterior translation was explained by bone-cartilage defects and meniscal
      degeneration. Relevant findings were the kinematic pattern differences between
      weight-bearing and open chained activities, suggesting that in biphasic muscle
      contraction and unloaded conditions, the function of the cruciate ligaments was
      not physiological. The kinematics of knees with medial OA and intact ACL differed
      from healthy knees. 

PMID- 25382362
TI  - Wear patterns in anteromedial osteoarthritis of the knee evaluated with CT
      arthrography.
AB  - OBJECTIVE: To analyze the value of CT-arthrography imaging in the diagnosis of
      knee osteoarthritis and to facilitate the selection of partial versus total knee
      replacement. METHODS: A retrospective study of 100 patients that had either
      medial unicompartmental knee replacement (UKR) (N=50) or total knee replacement
      (TKR) (N=50). One observer measured lower limb mechanical alignment and
      osteoarthritis patterns of the knee in each compartment with radiographs, CT
      arthrography and full leg standing radiographs. RESULTS: All patients had
      Kellgren-Lawrence grade IV osteoarthritis of the medial femorotibial joint with a
      mean (SD) varus alignment of the lower limb (172 degrees  (3.5 degrees ) HKA
      angle). Zone mechanical axis distribution showed strong correlation with HKA
      axis. Arthritis patterns were different for patients selected for UKR or TKR. UKR
      patients had anteromedial osteoarthritis and wear of the medial facet of the
      patella in contrast to TKR patients who had medial osteoarthritis associated with
      diffuse or lateral patellofemoral wear and wear of the central or posterior zones
      of the lateral compartment. Medial facet wear of the patella is related to more
      important varus alignment of the lower limb (Kennedy zone 0 and 1). CONCLUSION:
      CT-arthrography imaging can show lesions that are not visible on plain or stress
      radiographs because of central or posterior localization with surrounding intact
      cartilage. Patients who develop tri-compartmental osteoarthritis despite varus
      alignment have probably other risk factors than their mechanical alignment and
      should be considered candidates for TKR.

PMID- 25382363
TI  - A flat all-polyethylene tibial component in medial unicompartmental knee
      arthroplasty: a long-term study.
AB  - PURPOSE: The aim of this study is to present the clinical and radiological
      results of a cemented unicompartmental knee arthroplasty (UKA) using a flat all
      polyethylene tibial component at long-term follow-up, in a homogeneous group of
      patients with medial femoro-tibial knee arthritis. METHODS: The study group
      included 53 knees in 51 patients who were treated between January 1998 and
      November 1999 using a flat all-polyethylene tibial component. The same surgical
      technique was used for all patients. Inclusion criteria included a diagnosis of
      atraumatic arthritis, pre-operative flexion greater than 100 degrees  with no
      flexion deformity, a varus deformity of less than 10 degrees , and a body mass
      index (BMI) less than 35. A neutral mechanical axis was considered the end-point
      in all interventions. The patients were assessed clinically using the
      International Knee Society (IKS) and the functional scores at follow-up. Plain
      radiographs were used to determine the alignment of the mechanical axis at 5, 10
      and 14.7-year follow-up. A radiographic analysis of loosening, based on the
      method described by the IKS, was performed and the degree of arthritic
      progression in the non-resurfaced compartment was also assessed. RESULTS: At
      latest follow-up five patients had died and the data for three patients had not
      been collected. At final review four knees had undergone revision surgery and a
      further patient had declined a recommended revision TKA. The main indication for
      revision surgery was progressive aseptic loosening of the tibial component in
      female patients. No revisions were required because of arthritic progression in
      the lateral compartment. Over time the clinical outcomes did not show
      statistically significant differences. There was a significant worsening of the
      mechanical axis at the last follow-up compared with the results at five and ten
      year review. CONCLUSIONS: This study demonstrated that, in primary arthritis
      involving the medial femoro-tibial compartment, UKA using a flat all-polyethylene
      component could be considered an effective surgical option. Attention should be
      paid to progressive worsening of the mechanical axis over time associated with
      progressive radiolucency especially in female patients. LEVEL OF EVIDENCE: IV.

PMID- 25382364
TI  - Progression of medial osteoarthritis and long term results of lateral
      unicompartmental arthroplasty: 10 to 18 year follow-up of 54 consecutive
      implants.
AB  - INTRODUCTION: The literature results of unicompartmental knee arthroplasty (UKA)
      for isolated lateral osteoarthritis (OA) are not as good as for isolated medial
      OA. In 1988 our department started using a UKA with a fixed, all polyethylene
      tibial component and a resurfacing femoral component. The aim of this
      retrospective study is to report on the progression of medial OA and the long
      term results of this prosthesis implanted for isolated lateral OA, at a minimum
      follow up of ten years. MATERIALS AND METHODS: From January 1988 to October 2003,
      we performed 54 lateral UKAs in 52 patients. All patients had isolated lateral
      OA, which was post-traumatic in three cases. The mean age at the time of the
      index procedure was 72.2 +/- 15.2 years. Forty-six UKAs in 44 patients were
      available for follow-up. The mean duration of follow-up was 14.2 years (minimum
      ten years; range 10.2-18 years). RESULTS: At final follow-up, seven had undergone
      a second operation, three were revised to total knee arthroplasty (TKA), three
      had medial UKAs implanted for progression of medial disease, and one was
      converted to TKA for tibial tray malpositioning. No revision surgery was
      necessary for wear, infection or progression of patellofemoral OA. The mean Knee
      Society Score (KSS) knee score was 95.1 points and mean KSS function score was
      82.2 points. The mean range of motion was 132.6 degrees  (range, 115-150 degrees
      ). Implant survival was 94.4% at ten years and 91.4% at 15 years. CONCLUSION: The
      use of a UKA with a fixed, all polyethylene tibial bearing and a femoral
      resurfacing implant is a reliable option for the management of isolated lateral
      knee osteoarthritis. We have demonstrated excellent functional results and
      implant survival in the long term. The most significant factor leading to
      reoperation is progression of medial disease.

PMID- 25382365
TI  - Biomechanics of medial unicondylar in combination with patellofemoral knee
      arthroplasty.
AB  - PURPOSE: Modular bicompartmental knee arthroplasty (BKA) for treatment of medio
      patellofemoral osteoarthritis (OA) should allow for close to normal kinematics in
      comparison with unicondylar knee arthroplasty (UKA) and the native knee. There is
      so far no data to support this. SCOPE: Six fresh frozen full leg cadaver
      specimens were prepared and mounted in a kinematic rig with six degrees of
      freedom for the knee joint. Three motion patterns were applied with the native
      knee and after sequential implantation of medial UKA and patellofemoral joint
      replacement (PFJ): passive flexion-extension, open chain extension, and
      squatting. During the loaded motions, quadriceps and hamstrings muscle forces
      were applied. Infrared cameras continuously recorded the trajectories of marker
      frames rigidly attached to femur, tibia and patella. Prior computer tomography
      allowed identification of coordinate frames of the bones. Strains in the
      collateral ligaments were calculated from insertion site distances. RESULTS: UKA
      led to a less adducted and internally rotated tibia and a more strained medial
      collateral ligament (MCL). Addition of a patellofemoral replacement led to a more
      posterior position of both femoral condyles, a more dorsally located tibiofemoral
      contact point and higher MCL strain with squatting. CONCLUSION: In comparison to
      UKA modular BKA leads to a more dorsal tibial contact point, a medial femoral
      condyle being located more posteriorly, and more MCL strain. Mainly the changes
      to the trochlear anatomy as introduced by PFJ may account for these differences.

PMID- 25382366
TI  - Accuracy and early outcomes in medial unicompartmental knee arthroplasty
      performed using patient specific instrumentation.
AB  - Unicompartmental knee arthroplasty (UKA) is a technically demanding procedure and
      poor implant positioning has been identified as a factor in early failure. The
      aim of this study was to evaluate the accuracy and clinical outcomes of the
      patient specific instrumentation implementation technique with a fixed bearing
      UKA. We carried out a prospective study of 41 patients (44 procedures) between
      December 2011 and April 2013. The preoperative planned sizes of implants used
      were accurate to within one implant size change in 96% of cases. The mean post
      operative limb alignment was 3.8 degrees  varus. The Oxford Knee Scores (OKS) (0
      48) improved from a mean preoperative score of 23.8 to 35.6 at six weeks and 44.5
      at one year. The mean improvement in OKS from preoperative to one year was 20.7.
      The mean one year FJS (0-100) was 80.6. At a mean follow-up of 24 months there
      were no complications identified and there was a 100% survivorship. This
      technique may offer a particular advantage to surgeons who perform lower volumes
      of UKA with the potential to improve both clinical outcomes and implant
      survivorship in UKA to achieve greater consistency of results. 

PMID- 25382367
TI  - Cost-effectiveness of unicondylar versus total knee arthroplasty: a Markov model
      analysis.
AB  - BACKGROUND: Unicondylar knee arthroplasty (UKA) is believed to lead to less
      morbidity and enhanced functional outcomes when compared with total knee
      arthroplasty (TKA). Conversely, UKA is also associated with a higher revision
      risk than TKA. In order to further clarify the key differences between these
      separate procedures, the current study assessing the cost-effectiveness of UKA
      versus TKA was undertaken. METHODS: A state-transition Markov model was developed
      to compare the cost-effectiveness of UKA versus TKA for unicondylar
      osteoarthritis using a Belgian payer's perspective. The model was designed to
      include the possibility of two revision procedures. Model estimates were obtained
      through literature review and revision rates were based on registry data.
      Threshold analysis and probabilistic sensitivity analysis were performed to
      assess the model's robustness. RESULTS: UKA was associated with a cost reduction
      of ?2,807 and a utility gain of 0.04 quality-adjusted life years in comparison
      with TKA. Analysis determined that the model is sensitive to clinical
      effectiveness, and that a marginal reduction in the clinical performance of UKA
      would lead to TKA being the more cost-effective solution. CONCLUSION: UKA yields
      clear advantages in terms of costs and marginal advantages in terms of health
      effects, in comparison with TKA.

PMID- 25382368
TI  - Partial knee arthroplasty: patellofemoral arthroplasty and combined
      unicompartmental and patellofemoral arthroplasty implants--general considerations
      and indications, technique and clinical experience.
AB  - BACKGROUND: Unicompartmental and patellofemoral arthroplasty (PFA) are not new
      concepts as shown by different authors, and nowadays surgical solutions other
      than total knee arthroplasty (TKA) must be considered, exploiting the technical
      possibilities offered by the new designs of prostheses which have improved the
      results of already used, old fashioned implants. The aim of our study was to
      present our experience with PFA and its combination with unicompartmental knee
      arthroplasty (UKA). METHODS: From March 2007 to May 2012 we have treated 55
      patients with a patellofemoral joint arthroplasty; in 25 cases we have performed
      an isolated PFA and in 30 cases a combined UKA and PFA. The mean follow-up in the
      group of isolated patellofemoral joint arthroplasty was 56.5 months; in the
      combined implant the mean follow-up was 59 months. RESULTS: In both group we
      found an significant improvement of HSS, KSS and OKS scores with results at final
      follow-up ranging from good to excellent. CONCLUSIONS: Partial knee arthroplasty
      shows promising results at mid-term follow-up.

PMID- 25382369
TI  - Patellofemoral joint replacement, an evolving concept.
AB  - Isolated patellofemoral arthritis is a rare disease, whose management is
      challenging and controversial. Patellofemoral joint replacement can be an
      effective treatment for this condition. The very concept of a patellofemoral
      implant has evolved throughout the years, resulting in more anatomic designs and
      reproducible surgical techniques. The clinical outcomes of this procedure are
      strictly related to surgical indications, implant design and appropriate surgical
      technique. 

PMID- 25382370
TI  - Coronal alignment of patellofemoral arthroplasty.
AB  - BACKGROUND: Patellofemoral arthroplasty (PFA) can yield successful results in
      appropriately selected patients. The varus-valgus position or coronal alignment
      of the trochlear implant is determined by how its transitional edges articulate
      with the condylar cartilage. Whilst variation in condylar anatomy will not
      influence the axis of the lower limb in PFA, it can impact on the Q-angle of the
      PF joint. The aim of this study was to analyze how the coronal alignment can be
      influenced by the choice of anatomical landmarks. MATERIALS AND METHODS:
      Retrospective analysis of 57 PFAs with measurements of alignment from full leg
      radiographs. RESULTS: Coronal alignment following anterior condylar anatomy leads
      to a mean (SD) proximal valgus alignment of 100 degrees  (9 degrees ). Aligning
      the component with Whiteside's line gives a better alignment with less variance
      89 degrees  (3 degrees ). DISCUSSION: A trochlear component with a higher Q-angle
      compensates for patellar maltracking if the condylar anatomy would tend to put
      the implant in a more proximal varus or neutral position. If the trochlear
      component is proximally aligned in valgus this may have the opposite effect.
      Aligning the trochlear component with the AP-axis in the coronal plane avoids
      maltracking and optimally utilizes the design features of the implant. LEVEL OF
      EVIDENCE: Level III.

PMID- 25382371
TI  - A vertical two-thumb technique is superior to the two-thumb encircling technique
      for infant cardiopulmonary resuscitation.
AB  - AIM: The two-thumb encircling (TTE) technique often results in suboptimal cardiac
      compression and does not meet the requirements of current resuscitation
      guidelines. We compared this technique with the vertical two-thumb (VTT)
      technique, our novel modification of the TTE technique. METHODS: This was a
      prospective randomised crossover simulation study of out-of-hospital infant
      cardiopulmonary resuscitation (CPR). Participants who had completed a basic life
      support course performed 10 cycles of cardiac compressions on a manikin for each
      technique. RESULTS: We enrolled 36 medical doctors who had applied for a hospital
      internship in this study. The VTT generated significantly higher pressure than
      the TTE and the pressure difference ranged from 26.8 to 62.9 mmHg for each cycle,
      with a mean difference of 43.5 mmHg (95% CI, 37.8-49.2). The difference in
      pressure showed a tendency to increase with increasing cycles of cardiac
      compressions. The participants' heart and respiratory rate was higher with the
      VTT, but they said that it was easier to perform cardiac compressions with this
      technique. CONCLUSION: The VTT technique generated more pressure than the TTE
      technique in a simulated model of infant out-of-hospital CPR. It can provide an
      alternative compression technique for effective infant CPR, especially for the
      rescuers with small hands or a weak grip.

PMID- 25382372
TI  - The potential of circulating nucleic acids as components of companion diagnostics
      for predicting and monitoring chemotherapy response.
AB  - An effective personalized medicine is associated with the ability of identifying
      cancer patients who respond to anticancer targeted therapies. Therefore, new
      companion biomarkers that facilitate drug development are urgently needed. Since
      clinically relevant genetic and epigenetic alterations can be detected in cell
      free nucleic acids in the blood circulation of cancer patients, these molecules
      may be a new promising class of potential liquid biomarkers. They can be obtained
      in real-time from blood, and their analyses could, consequently, facilitate
      treatment decisions. Screening of these liquid biopsies may provide information
      on the aberrant signaling pathway that should be blocked by the chosen targeted
      therapy. This article will discuss the potential of circulating nucleic acids as
      therapeutics for overcoming chemotherapeutic resistance in anticancer strategies.

PMID- 25382374
TI  - iLOGP: a simple, robust, and efficient description of n-octanol/water partition
      coefficient for drug design using the GB/SA approach.
AB  - The n-octanol/water partition coefficient (log Po/w) is a key physicochemical
      parameter for drug discovery, design, and development. Here, we present a physics
      based approach that shows a strong linear correlation between the computed
      solvation free energy in implicit solvents and the experimental log Po/w on a
      cleansed data set of more than 17,500 molecules. After internal validation by
      five-fold cross-validation and data randomization, the predictive power of the
      most interesting multiple linear model, based on two GB/SA parameters solely, was
      tested on two different external sets of molecules. On the Martel druglike test
      set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and
      RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug
      test set, our model outperformed all compared empirical methodologies (N = 17, r
      = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA
      approach together with its predictive capacity, computational efficiency (1 to 2
      s per molecule), and tridimensional molecular graphics capability lay the
      foundations for a promising predictor, the implicit log P method (iLOGP), to
      complement the portfolio of drug design tools developed and provided by the SIB
      Swiss Institute of Bioinformatics. 

PMID- 25382375
TI  - Vaginal cones or balls to improve pelvic floor muscle performance and urinary
      continence in women postpartum: a quantitative systematic review and meta
      analysis protocol.
AB  - AIM: To identify, critically appraise and synthesize the best current evidence on
      the use of vaginal cones or balls to improve pelvic floor muscle performance and
      urinary continence in women post partum. BACKGROUND: The vaginal use of cones or
      balls is a pelvic floor muscle training method that aims to enhance muscle
      performance and thereby prevent or treat urinary incontinence. Nonetheless to
      date, no systematic review has focused on the effectiveness of these devices
      specifically during the postpartum period. DESIGN: Quantitative systematic review
      with potential meta-analysis. METHODS: The review will be undertaken by searching
      14 scientific databases (including PubMed and CINAHL, without date restriction)
      and the world-wide web; experts will also be contacted for published and
      unpublished data. Included studies must be randomized or quasi-randomized trials
      and have female participants until 1 year after childbirth. The intervention will
      be compared with no treatment, placebo, sham treatment or active controls.
      Outcome measures will relate to pelvic floor muscle performance or urinary
      incontinence. Studies will be selected, 'risk of bias' assessed and data
      extracted by two reviewers independently. Following inter-reviewer agreement of
      included studies, data will be checked after entry into systematic review
      processing software. If appropriate, data will be synthesized by meta-analysis;
      if this is not possible, a narrative review only will be undertaken. DISCUSSION:
      The information gained from this systematic review will help midwives, nurses,
      other health professionals and women after childbirth decide how to promote
      female pelvic floor health and in defining further areas of study.

PMID- 25382376
TI  - Acclimatisation-induced stress influenced host metabolic and gut microbial
      composition change.
AB  - Understanding the basal gut bacterial community structure and the host metabolic
      composition is pivotal for the interpretation of laboratory treatments designed
      to answer questions pertinent to host-microbe interactions. In this study, we
      report for the first time the underlying gut microbiota and systemic metabolic
      composition in BALB/c mice during the acclimatisation period. Our results showed
      that stress levels were reduced in the first three days of the study when the
      animals were subjected to repetitive handling daily but the stress levels were
      increased when handling was carried out at lower frequencies (weekly). We also
      observed a strong influence of stress on the host metabolism and commensal
      compositional variability. In addition, temporal biological compartmental
      variations in the responses were observed. Based on these results, we suggest
      that consistency in the frequency and duration of laboratory handling is crucial
      in murine models to minimise the impact of stress levels on the commensal and
      host metabolism dynamics. Furthermore, caution is advised in consideration of the
      temporal delay effect when integrating metagenomics and metabonomics data across
      different biological matrices (i.e. faeces and urine). 

PMID- 25382377
TI  - Gender effect on the scapular 3D posture and kinematic in healthy subjects.
AB  - Populations considered for shoulder analysis are often composed of various ratios
      of men and women. It is consequently hypothesized that gender has no significant
      effect on the joint kinematic. However, the literature reports, for the shoulder,
      differences in the range of motion between genders. The specific influence of
      gender on the scapulo-thoracic kinematics has not been studied yet. The dominant
      shoulder of two populations of men and women composed of 11 subjects each were
      evaluated in three dimensions for three distinct motions: flexion in the sagittal
      plane, abduction in the frontal plane and gleno-humeral internal/external
      rotation with the arm abducted at 90 degrees . Posture, kinematics and range of
      motion were studied separately. For flexion and abduction and with regard to the
      scapular kinematic, external rotation was significantly larger for women than
      men. The differences were of at least 5 degrees  at 120 degrees  of humeral
      elevation. Upward rotations were identical. Women also showed larger average
      active humero-thoracic range of motion. The mean differences were of 13 degrees ,
      7 degrees , 12 degrees  and 5 degrees  for abduction, flexion, internal rotation
      and external rotation, respectively. No difference was observed between the
      scapular resting positions of both populations. The observed differences
      concerning both the scapular and humeral patterns would indicate that the
      shoulder behaviour of men and women should not be expected to be similar. 

PMID- 25382378
TI  - Susceptibility to sulfuryl fluoride and lack of cross-resistance to phosphine in
      developmental stages of the red flour beetle, Tribolium castaneum (Coleoptera:
      Tenebrionidae).
AB  - BACKGROUND: Our aim was to ascertain the potential of sulfuryl fluoride (SF) as
      an alternative fumigant to manage phosphine-resistant pests. We tested the
      susceptibility of all life stages of red flour beetle, Tribolium castaneum
      (Herbst), to SF and assessed the presence of cross-resistance to this fumigant in
      phosphine-resistant strains of this species. RESULTS: Analysis of dose-response
      data indicated that the egg was the stage most tolerant to SF under a 48 h
      exposure period. At LC50 , eggs were 29 times more tolerant than other immature
      stages and adults, and required a relatively high concentration of 48.2 mg L(-1)
      for complete mortality. No significant differences in tolerance to SF were
      observed among the three larval instars, pupae and adults, and all of these
      stages were controlled at a low concentration of 1.32 mg L(-1) . Phosphine
      resistant strains did not show cross-resistance to SF. CONCLUSION: Our research
      concluded that the current maximum registered rate of SF, 1500 gh m(-3) , is
      adequate to control all the post-embryonic life stages of T. castaneum over a 48
      h fumigation period, but it will fail to achieve complete mortality of eggs,
      indicating the risk of some survival of eggs under this short exposure period. As
      there is no cross-resistance to SF in phosphine-resistant insects, it will play a
      key role in managing phosphine resistance in stored-grain insect pests.

PMID- 25382379
TI  - Optimal survival time-related cut-point with censored data.
AB  - In biomedical research and practice, continuous biomarkers are often used for
      diagnosis and prognosis, with a cut-point being established on the measurement to
      aid binary classification. When survival time is examined for the purposes of
      disease prognostication and is found to be related to the baseline measure of a
      biomarker, employing a single cut-point on the biomarker may not be very
      informative. Using survival time-dependent sensitivity and specificity, we extend
      a concordance probability-based objective function to select survival time
      related cut-points. To estimate the objective function with censored survival
      data, we adopt a non-parametric procedure for time-dependent receiver operational
      characteristics curves, which uses nearest neighbor estimation techniques. In a
      simulation study, the proposed method, when used to select a cut-point to
      optimally predict survival at a given time within a specified range, yields
      satisfactory results. We apply the procedure to estimate survival time-dependent
      cut-point on the prognostic biomarker of serum bilirubin among patients with
      primary biliary cirrhosis.

PMID- 25382381
TI  - Breathing simulator of workers for respirator performance test.
AB  - Breathing machines are widely used to evaluate respirator performance but they
      are capable of generating only limited air flow patterns, such as, sine,
      triangular and square waves. In order to evaluate the respirator performance in
      practical use, it is desirable to test the respirator using the actual breathing
      patterns of wearers. However, it has been a difficult task for a breathing
      machine to generate such complicated flow patterns, since the human respiratory
      volume changes depending on the human activities and workload. In this study, we
      have developed an electromechanical breathing simulator and a respiration
      sampling device to record and reproduce worker's respiration. It is capable of
      generating various flow patterns by inputting breathing pattern signals recorded
      by a computer, as well as the fixed air flow patterns. The device is equipped
      with a self-control program to compensate the difference in inhalation and
      exhalation volume and the measurement errors on the breathing flow rate. The
      system was successfully applied to record the breathing patterns of workers
      engaging in welding and reproduced the breathing patterns. 

PMID- 25382380
TI  - Inherited variation at MC1R and ASIP and association with melanoma-specific
      survival.
AB  - Melanocortin-1 receptor (MC1R) is a marker of melanoma risk in populations of
      European ancestry. However, MC1R effects on survival are much less studied. We
      investigated associations between variation at MC1R and survival in an
      international, population-based series of single primary melanoma patients
      enrolled into the Genes, Environment, and Melanoma study. MC1R genotype data was
      available for 2,200 participants with a first incident primary melanoma
      diagnosis. We estimated the association of MC1R genotypes with melanoma-specific
      survival (i.e., death caused by melanoma) and overall survival using COX
      proportional hazards modeling, adjusting for established prognostic factors for
      melanoma. We also conducted stratified analyses by Breslow thickness, tumor site,
      phenotypic index, and age. In addition, we evaluated haplotypes involving
      polymorphisms near the Agouti signaling protein gene (ASIP) locus for their
      impacts on survival. Melanoma-specific survival was inversely associated with
      carriage of MC1R variants in the absence of consensus alleles compared to
      carriage of at least one consensus allele (hazard ratio (HR) = 0.60; 95%
      confidence interval (CI): 0.40, 0.90). MC1R results for overall survival were
      consistent with no association. We did not observe any statistical evidence of
      heterogeneity of effect estimates in stratified analyses. We observed increased
      hazard of melanoma-specific death among carriers of the risk haplotype TG near
      the ASIP locus (HR = 1.37; 95% CI: 0.91, 2.04) when compared to carriers of the
      most common GG haplotype. Similar results were noted for overall survival. Upon
      examining the ASIP TG/TG diplotype, we observed considerably increased hazard of
      melanoma-specific death (HR = 5.11; 95% CI: 1.88, 13.88) compared to carriers of
      the most common GG/GG diplotype. Our data suggest improved melanoma-specific
      survival among carriers of two inherited MC1R variants. 

PMID- 25382382
TI  - Cross-national and longitudinal investigation of a short measure of workaholism.
AB  - The present study investigated the factor structure of the 10-item version of the
      Dutch Work Addiction Scale (DUWAS). The DUWAS-10 is intended to measure
      workaholism with two correlated factors: working excessively (WE) and working
      compulsively (WC). The factor structure of the DUWAS-10 was examined among multi
      occupational samples from the Netherlands (n=9,010) and Finland (n=4,567) using
      confirmatory factor analysis (CFA). CFAs revealed that the expected correlated
      two-factor solution showed satisfactory fit to the data. However, a second-order
      factor solution, where WE comprised the first-order factors "working frantically"
      and "working long hours", and WC the first-order factors "obsessive work drive"
      and "unease if not working", showed significantly better fit to the data. The
      expectation of factorial group invariance of the second-order factor structure
      between the Dutch and Finnish samples was also supported. Moreover, factorial
      time invariance was observed across a two-year time lag in a sub-sample of
      Finnish managers (n=459). In conclusion, the DUWAS-10 was found to be a
      comprehensive measure of workaholism, meeting the criteria of factorial validity
      in multiple settings, and can thus be recommended for use in both research and
      practice. 

PMID- 25382383
TI  - Effects of work stress and home stress on autonomic nervous function in Japanese
      male workers.
AB  - Autonomic imbalance is one of the important pathways through which psychological
      stress contributes to cardiovascular diseases/sudden death. Although previous
      studies have focused mainly on stress at work (work stress), the association
      between autonomic function and stress at home (home stress) is still poorly
      understood. The purpose was to clarify the effect of work/home stress on
      autonomic function in 1,809 Japanese male workers. We measured corrected QT (QTc)
      interval and QT index on the electrocardiogram along with blood pressure and
      heart rate. Participants provided self-reported information about the
      presence/absence of work/home stress and the possible confounders affecting QT
      indicators. Home stress was related positively to QT index (p=0.040) after
      adjusting for the possible confounders, though work stress did not show a
      significant relation to QTc interval or QT index. The odds ratio of home stress
      to elevated QT index (>=105) was 2.677 (95% CI, 1.050 to 6.822). Work/home stress
      showed no significant relation to blood pressure or heart rate. These findings
      suggest that autonomic imbalance, readily assessed by QT indicators, can be
      induced by home stress in Japanese workers. Additional research is needed to
      identify different types of home stress that are strongly associated with
      autonomic imbalance. 

PMID- 25382384
TI  - Multifactor leadership styles and new exposure to workplace bullying: a six-month
      prospective study.
AB  - This study investigated the prospective association between supervisor leadership
      styles and workplace bullying. Altogether 404 civil servants from a local
      government in Japan completed baseline and follow-up surveys. The leadership
      variables and exposure to bullying were measured by Multifactor Leadership
      Questionnaire and Negative Acts Questionnaire-Revised, respectively. The
      prevalence of workplace bullying was 14.8% at baseline and 15.1% at follow-up.
      Among respondents who did not experience bullying at baseline (n=216), those who
      worked under the supervisors as higher in passive laissez-faire leadership had a
      4.3 times higher risk of new exposure to bullying. On the other hand, respondents
      whose supervisors with highly considerate of the individual had a 70% lower risk
      of new exposure to bullying. In the entire sample (n=317), passive laissez-faire
      leadership was significantly and positively associated, while
      charisma/inspiration, individual consideration, and contingent reward were
      negatively associated both after adjusting for demographic and occupational
      characteristics at baseline, life events during follow-up, and exposure to
      workplace bullying at baseline. Results indicated that passive laissez-faire and
      low individual consideration leadership style at baseline were strong predictors
      of new exposure to bullying and high individual consideration leadership of
      supervisors/managers could be a preventive factor against bullying. 

PMID- 25382385
TI  - Population based analysis ependymoma patients in Alberta from 1975 to 2007.
AB  - BACKGROUND: Ependymomas are rare tumors of the central nervous system whose
      management is controversial. This population-based study of adults and children
      with ependymoma aims to (1) identify clinical and treatment-related factors that
      impact survival and (2) determine if postoperative radiotherapy (RT) can improve
      survival of patients with subtotal resection (STR) to levels similar to patients
      who had gross total resection (GTR). METHODS: This retrospective population-based
      study evaluated 158 patients with ependymoma diagnosed between 1975-2007 in
      Alberta, Canada. RESULTS: Younger patients (<7 years of age) were more likely to
      be diagnosed with grade III tumors compared with adults in whom grade I tumors
      were more common (p=0.003). Adults were more likely to have spinally located
      tumors compared to young children whose tumors were typically found in the brain.
      Overall, young children with ependymoma were more likely to die than older
      children or adults (p=0.001). An equivalent number of patients underwent GTR as
      compared with STR (48% vs 45%, respectively). Overall, older age, spinal tumor
      location, lower grade, and GTR were associated with improved progression free
      survival but only GTR was associated with significant improvement in overall
      survival. Median survival after STR and RT was 82 months compared with 122 months
      in patients who had GTR (p=0.0022). CONCLUSIONS: This is the first Canadian
      population-based analysis of patients with ependymoma including adults and
      children. Extent of resection appears to be the most important factor determining
      overall survival. Importantly, the addition of RT to patients initially treated
      with STR does not improve survival to levels similar to patients receiving GTR.

PMID- 25382386
TI  - Evaluation of three different manual techniques of sharpening curettes through a
      scanning electron microscope: a randomized controlled experimental study.
AB  - OBJECTIVE: The purpose of this study was to compare the effectiveness of three
      different techniques for manually sharpening of periodontal curettes (PCs) by
      examining the blades with the aid of scanning electron microscope (SEM). METHODS:
      Three groups were considered based on three sharpening methods used: group A
      (moving a PC over a stationary stone); group B (moving a stone over a stationary
      PC) and group C (moving a PC over a stone fixed, placed on a 'sharpening horse').
      After the sharpening, the blades were examined using SEM. The SEM images were
      assessed independently by five different independent observers. An evaluation
      board was used to assign a value to each image. A preliminary pilot study was
      conducted to establish the number of samples. Pearson's correlation test was used
      to assess the correlations between measurements. anova test with Bonferroni's
      post hoc test was used to compare the three groups. RESULTS: Sixty PCs (20 PCs
      per group) were used in this study. Statistically significant differences emerged
      between the three groups (P-value = 0.001). Bonferroni's test showed that the
      difference between groups A and B was not statistically significant (P-value =
      0.80), while it was significant for the comparisons between groups A and C (P
      value = 0.005) and between groups B and C (P-value = 0.001). CONCLUSIONS: The
      sharpening technique used in group C, which involved the use of the sharpening
      horse, proved the most effective.

PMID- 25382387
TI  - Long-term impact of human leukocyte antigen mismatches combined with expanded
      criteria donor on allograft outcomes in deceased donor kidney transplantation.
AB  - The long-term impact of human leukocyte antigen (HLA) mismatches combined with
      expanded criteria donors (ECD) on clinical outcomes has not been fully evaluated
      in recipients of deceased donor (DD) kidney transplantations. Of 595 DD renal
      transplant recipients in our center between 1991 and 2011, 210 recipients (36%)
      had 0-3 HLA mismatches/standard criteria donor (SCD), 353 (59%) had 4-6 HLA
      mismatches/SCD or 0-3 HLA mismatches/ECD, and 32 (5%) had 4-6 HLA mismatches/ECD.
      The mortality rate was significantly highest in the patients with 4-6 HLA
      mismatches/ECD (p = 0.040). The most common cause of death in this group was
      infection (50%). There were no significant differences in overall graft survival
      and death-censored graft survival. The biopsy-proven acute rejection rate was
      significantly higher in the 4-6 HLA mismatches/ECD group (p = 0.011). Cox
      regression multivariate analyses showed that 4-6 HLA mismatches plus ECD
      (adjusted hazard ratio [AHR], 3.2; 95% confidence interval [CI], 1.17-10.56) and
      diabetes (AHR, 4.3; 95% CI, 1.50-12.28) were significant predictors of recipient
      mortality. In conclusion, >=4 HLA mismatches plus ECD were associated with
      significantly higher rates of biopsy-proven acute rejection and mortality
      compared with other groups undergoing DD kidney transplantation. 

PMID- 25382388
TI  - Missing portion sizes in FFQ--alternatives to use of standard portions.
AB  - OBJECTIVE: Standard portions or substitution of missing portion sizes with
      medians may generate bias when quantifying the dietary intake from FFQ. The
      present study compared four different methods to include portion sizes in FFQ.
      DESIGN: We evaluated three stochastic methods for imputation of portion sizes
      based on information about anthropometry, sex, physical activity and age. Energy
      intakes computed with standard portion sizes, defined as sex-specific medians
      (median), or with portion sizes estimated with multinomial logistic regression
      (MLR), 'comparable categories' (Coca) or k-nearest neighbours (KNN) were compared
      with a reference based on self-reported portion sizes (quantified by a
      photographic food atlas embedded in the FFQ). SETTING: The Danish Health
      Examination Survey 2007-2008. SUBJECTS: The study included 3728 adults with
      complete portion size data. RESULTS: Compared with the reference, the root-mean
      square errors of the mean daily total energy intake (in kJ) computed with portion
      sizes estimated by the four methods were (men; women): median (1118; 1061), MLR
      (1060; 1051), Coca (1230; 1146), KNN (1281; 1181). The equivalent biases (mean
      error) were (in kJ): median (579; 469), MLR (248; 178), Coca (234; 188), KNN (
      340; 218). CONCLUSIONS: The methods MLR and Coca provided the best agreement with
      the reference. The stochastic methods allowed for estimation of meaningful
      portion sizes by conditioning on information about physiology and they were
      suitable for multiple imputation. We propose to use MLR or Coca to substitute
      missing portion size values or when portion sizes needs to be included in FFQ
      without portion size data.

PMID- 25382390
TI  - Intrathecal Pump: An Abrupt Intermittent Pump Failure.
AB  - SETTING: Intrathecal baclofen is an established method of treating spasticity.
      However, this therapy is not without significant morbidity and mortality. The
      known morbidity associated with intrathecal pumps includes death, infection, and
      sepsis including central nervous system infection, accidental overdose, wrong
      drug administration as well as technical failures such as pump or battery
      failure, catheter migration or catheter breakage. Medtronic has issued a number
      of advisories, most recently in June 2013, regarding the safety of the Medtronic
      SynchroMed II intrathecal pumps. PATIENT: Sixty-four months post insertion of a
      SynchroMed II, model 8637; our patient was reviewed as a matter of urgency by our
      team, as he was complaining of worsening spasticity and pain. The device was
      interrogated and this indicated a motor stall at the time of interrogation. The
      interrogation also revealed that this was the third period of motor stall in the
      preceding three days. According to the patient, and consistent with our
      interrogation, the device had been alarming intermittently for the previous three
      days. INTERVENTION: He was commenced on oral baclofen overnight, which gave some
      improvement to his symptoms. A replacement intrathecal pump was inserted the
      following day. This provided the patient with his usual level of relief. The
      product Engineering Department at Medtronic reviewed the original pump. OUTCOME:
      The patient's new intrathecal pump has been functioning uneventfully since its
      replacement and he continues to receive good symptom relief from his new pump.
      Internal inspection of the pump by the Engineering Department at Medtronic
      revealed corrosion of the motor gearbox. CONCLUSION: Our unit continues to retain
      a high level of vigilance when dealing with potential complications of
      intrathecal pump therapy. Supplemental oral baclofen may have a role in this
      setting.

PMID- 25382389
TI  - Density- and trait-mediated effects of a parasite and a predator in a tri-trophic
      food web.
AB  - Despite growing interest in ecological consequences of parasitism in food webs,
      relatively little is known about effects of parasites on long-term population
      dynamics of non-host species or about whether such effects are density or trait
      mediated. We studied a tri-trophic food chain comprised of (i) a bacterial basal
      resource (Serratia fonticola), (ii) an intermediate consumer (Paramecium
      caudatum), (iii) a top predator (Didinium nasutum) and (iv) a parasite of the
      intermediate consumer (Holospora undulata). A fully factorial experimental
      manipulation of predator and parasite presence/absence was combined with analyses
      of population dynamics, modelling and analyses of host (Paramecium) morphology
      and behaviour. Predation and parasitism each reduced the abundance of the
      intermediate consumer (Paramecium), and parasitism indirectly reduced the
      abundance of the basal resource (Serratia). However, in combination, predation
      and parasitism had non-additive effects on the abundance of the intermediate
      consumer, as well as on that of the basal resource. In both cases, the negative
      effect of parasitism seemed to be effaced by predation. Infection of the
      intermediate consumer reduced predator abundance. Modelling and additional
      experimentation revealed that this was most likely due to parasite reduction of
      intermediate host abundance (a density-mediated effect), as opposed to changes in
      predator functional or numerical response. Parasitism altered morphological and
      behavioural traits, by reducing host cell length and increasing the swimming
      speed of cells with moderate parasite loads. Additional tests showed no
      significant difference in Didinium feeding rate on infected and uninfected hosts,
      suggesting that the combination of these modifications does not affect host
      vulnerability to predation. However, estimated rates of encounter with Serratia
      based on these modifications were higher for infected Paramecium than for
      uninfected Paramecium. A mixture of density-mediated and trait-mediated indirect
      effects of parasitism on non-host species creates rich and complex possibilities
      for effects of parasites in food webs that should be included in assessments of
      possible impacts of parasite eradication or introduction. 

PMID- 25382391
TI  - Benefit-Cost Analysis of Foot and Mouth Disease Control in Large Ruminants in
      Cambodia.
AB  - Foot and mouth disease (FMD) is endemic in Cambodia and throughout the Greater
      Mekong Subregion and causes significant losses to rural smallholders owning the
      majority of the national large ruminant population. However, due to
      underreporting, paucity of knowledge of FMD impacts, limited veterinary capacity
      and deficits of data available for analysis, the quantifiable benefits of a
      national FMD control programme are unknown. To address this deficit, existing
      literature and research data from the 'Best practice health and husbandry of
      cattle, Cambodia' project conducted between 2007 and 2012, were used to develop a
      three-phase analysis framework to: assess the impacts of the recent widespread
      FMD epizootic in Cambodia in 2010, conduct a value chain analysis of the large
      ruminant market and estimate the costs and benefits for a national large ruminant
      biannual FMD vaccination programme. A trader survey conducted in 2010-2011
      provided cattle and buffalo value chain information and was matched to village
      herd structure data to calculate a total large ruminant farm-gate value of USD
      1.271 billion in 2010. Monte Carlo simulation modelling that implemented a 5-year
      biannual vaccination programme at a cost of USD 6.3 an animal per year identified
      a benefit-cost ratio of 1.40 (95% CI 0.96-2.20) when accounting for recent prices
      of cattle and buffalo in Cambodia and based on an expected annual incidence of
      0.2 (assuming one major epizootic in the 5-year vaccination programme). Given
      that the majority of the large ruminants are owned by rural smallholders, and
      mostly the poor are involved in agricultural employment, the successful
      implementation of an FMD control programme in Cambodia would be expected to avoid
      estimated losses of USD 135 million; equivalent to 10.6% of the 2010 farm-gate
      value and contributing to important reductions in rural poverty and food
      insecurity. 

PMID- 25382392
TI  - Dimethyl fumarate for treating relapsing multiple sclerosis.
AB  - INTRODUCTION: Outcomes of two large double-blind placebo-controlled studies of
      oral dimethyl fumarate (DMF) in multiple sclerosis (MS) provided the basis for
      its marketing approval as Tecfidera(r) by the US FDA in early 2013 and the
      European Medicines Agency in February 2014. The safety of DMF is complemented by
      experience in the use of an oral mixture of fumaric acid esters, including DMF
      for psoriasis (Fumaderm(r); DMF and monoethyl fumarate [DMF-MEF]) licensed in
      Germany in 1994. AREAS COVERED: This article reviews the pivotal trials leading
      to the approval of DMF for MS and the pharmacological literature related to the
      extensive use of oral fumaric acid esters for psoriasis over the last quarter
      century. Anecdotal reports of serious adverse reactions to DMF-MEF are also
      reviewed in this report. EXPERT OPINION: DMF is generally safe and well
      tolerated. Flushing and gastrointestinal side effects are relatively common for
      the approved DMF dose but are ordinarily mild and self-limited. No increase in
      malignancies has been reported despite theoretical concerns. Although progressive
      multifocal encephalopathy has been reported anecdotally in 5 of > 196,000 patient
      years of experience with fumaric acid esters, none of the 65,000 DMF MS patients
      treated in the first year has been affected. Appendix to the abstract: Subsequent
      to the acceptance of this article for publication, the manufacturer has notified
      physicians of the death of one patient from PML complicating use of DMF in the
      DEFINE study extension (ENDORSE). This does not alter the expert opinion rendered
      regarding the safety of DMF. We await the outcomes and recommendations from the
      ongoing investigation into this case.

PMID- 25382393
TI  - Gross and net production during the spring bloom along the Western Antarctic
      Peninsula.
AB  - This study explores some of the physiological mechanisms responsible for high
      productivity near the shelf in the Western Antarctic Peninsula despite a short
      growing season and cold temperature. We measured gross and net primary production
      at Palmer Station during the summer of 2012/2013 via three different techniques:
      incubation with H2 (18) O; incubation with (14) CO2 ; and in situ measurements of
      O2 /Ar and triple oxygen isotope. Additional laboratory experiments were
      performed with the psychrophilic diatom Fragilariopsis cylindrus. During the
      spring bloom, which accounted for more than half of the seasonal gross production
      at Palmer Station, the ratio of net-to-gross production reached a maximum greater
      than c. 60%, among the highest ever reported. The use of multiple techniques
      showed that these high ratios resulted from low heterotrophic respiration and
      very low daylight autotrophic respiration. Laboratory experiments revealed a
      similar ratio of net-to-gross O2 production in F. cylindrus and provided the
      first experimental evidence for an important level of cyclic electron flow (CEF)
      in this organism. The low ratio of community respiration to gross primary
      production observed during the bloom at Palmer Station may be characteristic of
      high latitude coastal ecosystems and partially supported by a very active CEF in
      psychrophilic phytoplankton.

PMID- 25382394
TI  - Ca-Ca interaction in inverse sandwich Ca-C8H8-Ca.
AB  - The inverse sandwich Ca-C8H8-Ca is predicted to be an open-shell singlet state.
      Since the C8H8 ligand prevents the spin-up and spin-down electrons of different
      calcium atoms from forming Ca-Ca bonds, the spin-coupling electrons lead to a
      singlet diradical character. The metal-ligand interaction contributes to the
      stability of Ca-C8H8-Ca against dissociation and isomerization. For the
      coordination complex (DME)3Ca-C8H8-Ca(DME)3, the open-shell singlet state is
      unavailable, while the closed-shell singlet state with direct Ca-Ca bonds is more
      favorable, because dimethyl ether molecules could push the spin-paired electrons
      of different calcium atoms to migrate towards the direction of Ca-Ca bonding. For
      Ca-C4H4-Ca, the ground state is an open-shell singlet state, of which the
      diradical character is very similar to that of Ca-C8H8-Ca. For (DME)3Ca-C4H4
      Ca(DME)3, the lowest energy is the triplet state. 

PMID- 25382400
TI  - Stitching graphene oxide sheets into a membrane at a liquid/liquid interface.
AB  - Layer-by-layer patterned GO membrane assembling at a liquid/liquid interface was
      realized using polyetheramine "stitching" molecules with an adjustable
      hydrophobicity and its thickness can be easily tuned from nanometer to micrometer
      by controlling reaction kinetics including reactant concentration, reaction time
      and reaction temperature. 

PMID- 25382395
TI  - A fluorescent indicator for imaging lysosomal zinc(II) with Forster resonance
      energy transfer (FRET)-enhanced photostability and a narrow band of emission.
AB  - We demonstrate a strategy to transfer the zinc(II) sensitivity of a
      fluoroionophore with low photostability and a broad emission band to a bright and
      photostable fluorophore with a narrow emission band. The two fluorophores are
      covalently connected to afford an intramolecular Forster resonance energy
      transfer (FRET) conjugate. The FRET donor in the conjugate is a zinc(II)
      sensitive arylvinylbipyridyl fluoroionophore, the absorption and emission of
      which undergo bathochromic shifts upon zinc(II) coordination. When the FRET donor
      is excited, efficient intramolecular energy transfer occurs to result in the
      emission of the acceptor boron dipyrromethene (4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene or BODIPY) as a function of zinc(II) concentration. The broad emission
      band of the donor/zinc(II) complex is transformed into the strong, narrow
      emission band of the BODIPY acceptor in the FRET conjugates, which can be
      captured within the narrow emission window that is preferred for multicolor
      imaging experiments. In addition to competing with other nonradiative decay
      processes of the FRET donor, the rapid intramolecular FRET of the excited FRET
      conjugate molecule protects the donor fluorophore from photobleaching, thus
      enhancing the photostability of the indicator. FRET conjugates 3 and 4 contain
      aliphatic amino groups, which selectively target lysosomes in mammalian cells.
      This subcellular localization preference was verified by using confocal
      fluorescence microscopy, which also shows the zinc(II)-enhanced emission of 3 and
      4 in lysosomes. It was further shown using two-color structured illumination
      microscopy (SIM), which is capable of extending the lateral resolution over the
      Abbe diffraction limit by a factor of two, that the morpholino-functionalized
      compound 4 localizes in the interior of lysosomes, rather than anchoring on the
      lysosomal membranes, of live HeLa cells. 

PMID- 25382401
TI  - Sensitive determination of atorvastatin in human plasma by dispersive liquid
      liquid microextraction and solidification of floating organic drop followed by
      high-performance liquid chromatography.
AB  - A novel and sensitive dispersive liquid-liquid microextraction method based on
      the solidification of the floating organic drop combined with high-performance
      liquid chromatography and ultraviolet detection was used for the determination of
      atorvastatine in blood serum samples. The chromatographic separation of
      atorvastatin was carried out using methanol as the mobile phase organic modifier.
      Various parameters affecting the extraction efficiency were optimized, such as
      the kind and volume of extraction solvent (1-undecanol) and disperser solvent
      (acetonitrile), pH, and the extraction time. The calibration curve was linear in
      the range of 0.2-6000 MUg/L of atorvastatin (r(2) = 0.995) with a limit of
      detection of 0.07 MUg/L. The relative standard deviation for 100 MUg/L of
      atorvastatin in human plasma was 8.4% (n = 4). The recoveries of plasma samples
      spiked with atorvastatin were in the range of 98.8-113.8%. The obtained results
      showed that the proposed method is fast, simple, and reliable for the
      determination of very low concentrations of atorvastatin in human plasma samples.

PMID- 25382402
TI  - Long-term cholecalciferol administration in hemodialysis patients: a single
      center randomized pilot study.
AB  - BACKGROUND: Data on the potent pleiotropic extraskeletal effects of vitamin D
      have renewed interest in its use in selected populations, including patients with
      chronic kidney disease, but the available data are still insufficient to make
      recommendations. This study assessed the long-term effect of small
      cholecalciferol doses on serum vitamin D, parathormone (PTH), and bone mineral
      density (BMD) in hemodialysis patients. MATERIAL/METHODS: Nineteen patients with
      serum 25(OH)D <20 ng/mL were randomized into cholecalciferol (2000 IU 3*/week)
      and no-treatment groups, then observed for 1 year. Patients with hypercalcemia,
      hyperphosphatemia, and receiving vitamin D/calcimimetics were excluded. Serum
      25(OH)D, 1,25(OH)2D, PTH, and alkaline phosphatase activity were examined every 2
      months and BMD was measured before and after the study. RESULTS: We observed
      normalization of serum 25(OH)D with an increase in medians from 11.3 to 44.9
      ng/mL (P=0.02) in the cholecalciferol group and no change in the controls
      (P<0.001). Simultaneously, median serum 1,25(OH)2D increased from 18.2 to 43.1
      pmol/L (P=0.02) in the cholecalciferol group and from 10.6 to 21.2 pmol/L
      (P=0.02) in controls (P=0.013). The treatment was associated with a small
      increase in serum calcium, but serum phosphate, PTH, alkaline phosphatase, and
      BMD remained unchanged in both groups. CONCLUSIONS: Oral cholecalciferol at a
      dose of 2000 IU/3*/week is an effective and safe way to treat vitamin D
      deficiency in hemodialysis patients, leading to a significant increase in serum
      1,25(OH)2D. However, it was insufficient to suppress the activity of parathyroid
      glands or to significantly change BMD.

PMID- 25382403
TI  - The spectral-structural relationship of a series of oxyluciferin derivatives.
AB  - The absorption and emission spectra of a series of oxyluciferin derivatives with
      different substituents, as well as 6'-amino oxyluciferins in different enol and
      keto forms, with or without an active-site model of luciferase, were
      systematically investigated using density functional theory. The effects of
      substituents, microenvironment, and the luciferase on the structures, absorption
      spectra, and fluorescent emission were all taken into account. It was found that
      a wide range of emission colors can be obtained from various oxyluciferin
      derivatives with the inclusion of active site residues modeling the luciferase
      active site. Enol and keto forms are responsible for the emissions observed in
      experiments. It was suggested that the active site of luciferase must be included
      in the calculation in order to determine the form of the emitters. 

PMID- 25382404
TI  - Hypoglycaemic activity of culinary Pleurotus ostreatus and P. cystidiosus
      mushrooms in healthy volunteers and type 2 diabetic patients on diet control and
      the possible mechanisms of action.
AB  - This study determined the oral hypoglycaemic effect of suspensions of freeze
      dried and powdered (SFDP) Pleurotus ostreatus (P.o) and Pleurotus cystidiosus
      (P.c), using healthy human volunteers and Type 2 diabetic patients on diet
      control at a dose of 50 mg/kg/body weight, followed by a glucose load. The
      possible hypoglycaemic mechanisms were evaluated using rats, by examining
      intestinal glucose absorption and serum levels of insulin, glucokinase (GK) and
      glycogen synthase kinase (GSK). The P.o and P.c showed a significant reduction (P
      < 0.05) in fasting and postprandial serum glucose levels of healthy volunteers
      and reduced the postprandial serum glucose levels and increased the serum insulin
      levels (P < 0.05) of Type 2 diabetic patients. The P.o and P.c increased the
      intestinal absorption of glucose but simultaneously reduced the serum glucose
      levels (P < 0.05) in rats. Both mushrooms reduced the serum GSK and promoted
      insulin secretion while P.c increased serum GK (P < 0.05). The hypoglycaemic
      activity of P.o and P.c makes mushrooms beneficial functional foods in diabetes
      mellitus. The mechanism of hypoglycaemic activity of P.o and P.c is possibly by
      increasing GK activity and promoting insulin secretion and thereby increasing the
      utilization of glucose by peripheral tissues, inhibiting GSK and promoting
      glycogen synthesis.

PMID- 25382405
TI  - How does hybrid bridging core modification enhance the nonlinear optical
      properties in donor-pi-acceptor configuration? A case study of dinitrophenol
      derivatives.
AB  - This study spotlights the fundamental insights about the structure and static
      first hyperpolarizability (beta) of a series of 2,4-dinitrophenol derivatives (1
      5), which are designed by novel bridging core modifications. The central bridging
      core modifications show noteworthy effects to modulate the optical and nonlinear
      optical properties in these derivatives. The derivative systems show
      significantly large amplitudes of first hyperpolarizability as compared to parent
      system 1, which are 4, 46, 66, and 90% larger for systems 2, 3, 4, and 5,
      respectively, at Moller-Plesset (MP2)/6-31G* level of theory. The static first
      hyperpolarizability and frequency dependent coupled-perturbed Kohn-Sham first
      hyperpolarizability are calculated by means of MP2 and density functional theory
      methods and compared with respective experimental values wherever possible. Using
      two-level model with full-set of parameters dependence of transition energy
      (DeltaEpsilon), transition dipole moment (MU(0)) as well as change in dipole
      moment from ground to excited state (DeltaMU), the origin of increase in beta
      amplitudes is traced from the change in dipole moment from ground to excited
      state. The causes of change in dipole moments are further discovered through sum
      of Mulliken atomic charges and intermolecular charge transfer spotted in frontier
      molecular orbitals analysis. Additionally, analysis of conformational isomers and
      UV-Visible spectra has been also performed for all designed derivatives. Thus,
      our present investigation provides novel and explanatory insights on the chemical
      nature and origin of intrinsic nonlinear optical (NLO) properties of 2,4
      dinitrophenol derivatives.

PMID- 25382406
TI  - Antibody induced pain in children: An opportunity to study pain mechanism, IgG
      design and analgesics.

PMID- 25382407
TI  - Respiratory proteomics: from descriptive studies to personalized medicine.
AB  - Respiratory diseases are highly prevalent and affect humankind worldwide, causing
      extensive morbidity and mortality with the environment playing an important role.
      Given the complex structure of the airways, sophisticated tools are required for
      early diagnosis; initial symptoms are nonspecific, and the clinical diagnosis is
      made frequently late. Over the past few years, proteomics has made high
      technological progress in mass-spectrometry-based protein identification and has
      allowed us to gain new insights into disease mechanisms and identify potential
      novel therapeutic targets. This review will highlight the contributions of
      proteomics toward the understanding of the respiratory proteome listing potential
      biomarkers and its potential application to the clinic. We also outline the
      contributions of proteomics to creating a personalized approach in respiratory
      medicine. 

PMID- 25382408
TI  - Serotonin-2C receptor agonists decrease potassium-stimulated GABA release in the
      nucleus accumbens.
AB  - The serotonin 5-HT2C receptor has shown promise in vivo as a pharmacotherapeutic
      target for alcoholism. For example, recently, a novel 4-phenyl-2-N,N
      dimethylaminotetralin (PAT) drug candidate, that demonstrates 5-HT2C receptor
      agonist activity together with 5-HT2A/2B receptor inverse agonist activity, was
      shown to reduce operant responding for ethanol after peripheral administration to
      rats. Previous studies have shown that the 5-HT2C receptor is found throughout
      the mesoaccumbens pathway and that 5-HT2C receptor agonism causes activation of
      ventral tegmental area (VTA) GABA neurons. It is unknown what effect 5-HT2C
      receptor modulation has on GABA release in the nucleus accumbens core (NAcc). To
      this end, microdialysis coupled to capillary electrophoresis with laser-induced
      fluorescence was used to quantify extracellular neurotransmitter concentrations
      in the NAcc under basal and after potassium stimulation conditions, in response
      to PAT analogs and other 5-HT2C receptor modulators administered by reverse
      dialysis to rats. 5-HT2C receptor agonists specifically attenuated stimulated
      GABA release in the NAcc while 5-HT2C antagonists or inverse agonists had no
      effect. Agents with activity at 5-HT2A receptors had no effect on GABA release.
      Thus, in contrast to results reported for the VTA, current results suggest 5-HT2C
      receptor agonists decrease stimulated GABA release in the NAcc, and provide a
      possible mechanism of action for 5HT2C -mediated negative modulation of ethanol
      self-administration.

PMID- 25382410
TI  - Capsule endoscopy is safe in patients with cardiac pacemakers and implantable
      cardioverter defibrillators.

PMID- 25382409
TI  - Recombination, chromosome number and eusociality in the Hymenoptera.
AB  - Extraordinarily high rates of recombination have been observed in some eusocial
      species. The most popular explanation is that increased recombination increases
      genetic variation among workers, which in turn increases colony performance, for
      example by increasing parasite resistance. However, support for the generality of
      higher recombination rates among eusocial organisms remains weak, due to low
      sample size and a lack of phylogenetic independence of observations.
      Recombination rate, although difficult to measure directly, is correlated with
      chromosome number. As predicted, several authors have noted that chromosome
      numbers are higher among the eusocial species of Hymenoptera (ants, bees and
      wasps). Here, we present a formal comparative analysis of karyotype data from
      1567 species of Hymenoptera. Contrary to earlier studies, we find no evidence for
      an absolute difference between chromosome number in eusocial and solitary species
      of Hymenoptera. However, we find support for an increased rate of chromosome
      number change in eusocial taxa. We show that among eusocial taxa colony size is
      able to explain some of the variation in chromosome number: intermediate-sized
      colonies have more chromosomes than those that are either very small or very
      large. However, we were unable to detect effects of a number of other colony
      characteristics predicted to affect recombination rate - including colony
      relatedness and caste number. Taken together, our results support the view that a
      eusocial lifestyle has led to variable selection pressure for increased
      recombination rates, but that identifying the factors contributing to this
      variable selection will require further theoretical and empirical effort. 

PMID- 25382411
TI  - Highly accelerated inverse electron-demand cycloaddition of electron-deficient
      azides with aliphatic cyclooctynes.
AB  - Strain-promoted azide-alkyne cycloaddition (SPAAC) as a conjugation tool has
      found broad application in material sciences, chemical biology and even in vivo
      use. However, despite tremendous effort, SPAAC remains fairly slow (0.2-0.5 M(-1)
      s(-1)) and efforts to increase reaction rates by tailoring of cyclooctyne
      structure have suffered from a poor trade-off between cyclooctyne reactivity and
      stability. We here wish to report tremendous acceleration of strain-promoted
      cycloaddition of an aliphatic cyclooctyne (bicyclo[6.1.0]non-4-yne, BCN) with
      electron-deficient aryl azides, with reaction rate constants reaching 2.0-2.9 M(
      1) s(-1). A remarkable difference in rate constants of aliphatic cyclooctynes
      versus benzoannulated cyclooctynes is noted, enabling a next level of
      orthogonality by a judicious choice of azide-cyclooctyne combinations, which is
      inter alia applied in one-pot three-component protein labelling. The pivotal role
      of azide electronegativity is explained by density-functional theory calculations
      and electronic-structure analyses, which indicates an inverse electron-demand
      mechanism is operative with an aliphatic cyclooctyne. 

PMID- 25382412
TI  - Broad integration of expression maps and co-expression networks compassing novel
      gene functions in the brain.
AB  - Using a recently invented technique for gene expression mapping in the whole
      anatomy context, termed transcriptome tomography, we have generated a dataset of
      36,000 maps of overall gene expression in the adult-mouse brain. Here, using an
      informatics approach, we identified a broad co-expression network that follows an
      inverse power law and is rich in functional interaction and gene-ontology terms.
      Our framework for the integrated analysis of expression maps and graphs of co
      expression networks revealed that groups of combinatorially expressed genes,
      which regulate cell differentiation during development, were present in the adult
      brain and each of these groups was associated with a discrete cell types. These
      groups included non-coding genes of unknown function. We found that these genes
      specifically linked developmentally conserved groups in the network. A previously
      unrecognized robust expression pattern covering the whole brain was related to
      the molecular anatomy of key biological processes occurring in particular areas. 

PMID- 25382413
TI  - Informational needs of gastrointestinal oncology patients.
AB  - OBJECTIVES: In response to the dearth of consumer health information for patients
      with gastrointestinal cancers, this study examined the informational needs of
      these patients to build a plan for future resource development. Although studies
      have examined informational needs of some such cancers, no published literature
      has investigated the comprehensive informational needs across all sites of
      gastrointestinal cancer. METHODS: A cross-sectional needs assessment comprising a
      self-administered questionnaire was conducted at an ambulatory gastrointestinal
      oncology clinic in Toronto, Canada. Patient informational needs were measured,
      including importance of information, amount desired and preferred mode of
      delivery. Informational needs were grouped into six domains: medical, practical,
      physical, emotional, social and spiritual. RESULTS: Eighty-two surveys were
      analysed. The majority of the respondents were male (53.8%), over the age of 50
      (77.8%), and born outside of Canada (51.9%). While many did not speak English as
      a child (46.3%), and do not speak English at home (22.2%), nearly all indicated
      comfort with receiving health information in English (97.5%). The majority of
      respondents were college educated (79.3%) and married (73%). Multiple cancer
      types were reported; the most common being colorectal (39%), followed by
      pancreatic (12%) and cancers of the gallbladder or bile duct (12%). Overall,
      respondents placed highest importance on medical information (P < 0.001).
      Preferred education modalities were pamphlets, websites and one-on-one
      discussions with health-care professionals. CONCLUSIONS: This study highlights
      the principal informational needs of patients with gastrointestinal malignancies,
      along with preferred modality for information delivery. This information will
      guide the development of educational resources for future patients.

PMID- 25382414
TI  - SEARCHing for Solutions: applying a novel person-centered analysis to the problem
      of dropping out of preventive parent education.
AB  - Behavioral parent training is an effective intervention for many child behavior
      problems; however, low parent attendance and premature termination of
      intervention have been chronic barriers to successful implementation.
      Socioeconomic factors, demographic characteristics, social support, stressful
      life events, and parental depression have all been identified in prior research
      as risk factors for premature termination. The present study tested whether these
      risk factors were valid predictors in a targeted prevention sample using a novel
      methodology, a binary segmentation procedure (SEARCH), to identify meaningful
      subgroups within the sample. The SEARCH procedure, a person-centered approach to
      analysis, resulted in five mutually exclusive groups. These groups were
      classified based on social support and stressful life events, and group
      membership significantly predicted attendance at parent training. Other
      frequently studied predictors, such as income, were not significant predictors
      within this sample. The groups which were characterized by higher social support
      and fewer life events typically attended more sessions; however, the relationship
      between these risk factors was not linear and would not have been detected by
      many other methods of analysis. These findings both contribute to the overall
      literature on parent training preventions, and suggest that binary segmentation
      procedures, such as SEARCH, may have widespread utility in prevention research
      because such procedures allow for the detection of non-linear interactions
      between risk factors. 

PMID- 25382415
TI  - Cost-benefit analysis of a preventive intervention for divorced families:
      reduction in mental health and justice system service use costs 15 years later.
AB  - This cost-benefit analysis compared the costs of implementing the New Beginnings
      Program (NBP), a preventive intervention for divorced families to monetary
      benefits saved in mental healthcare service use and criminal justice system
      costs. NBP was delivered when the offspring were 9-12 years old. Benefits were
      assessed 15 years later when the offspring were young adults (ages 24-27). This
      study estimated the costs of delivering two versions of NBP, a single-component
      parenting-after-divorce program (Mother Program, MP) and a two-component
      parenting-after-divorce and child-coping program (Mother-Plus-Child Program,
      MPCP), to costs of a literature control (LC). Long-term monetary benefits were
      determined from actual expenditures from past-year mental healthcare service use
      for mothers and their young adult (YA) offspring and criminal justice system
      involvement for YAs. Data were gathered from 202 YAs and 194 mothers (75.4 % of
      families randomly assigned to condition). The benefits, as assessed in the 15th
      year after program completion, were $1630/family (discounted benefits
      $1077/family). These 1-year benefits, based on conservative assumptions, more
      than paid for the cost of MP and covered the majority of the cost of MPCP.
      Because the effects of MP versus MPCP on mental health and substance use problems
      have not been significantly different at short-term or long-term follow-up
      assessments, program managers would likely choose the lower-cost option. Given
      that this evaluation only calculated economic benefit at year 15 and not the
      previous 14 (nor future years), these findings suggest that, from a societal
      perspective, NBP more than pays for itself in future benefits.

PMID- 25382416
TI  - Pathogens under stress.

PMID- 25382417
TI  - Identification of recurrent truncated DDX3X mutations in chronic lymphocytic
      leukaemia.

PMID- 25382418
TI  - Extended reaction scope of thiamine diphosphate dependent cyclohexane-1,2-dione
      hydrolase: from C-C bond cleavage to C-C bond ligation.
AB  - ThDP-dependent cyclohexane-1,2-dione hydrolase (CDH) catalyzes the C?C bond
      cleavage of cyclohexane-1,2-dione to 6-oxohexanoate, and the asymmetric benzoin
      condensation between benzaldehyde and pyruvate. One of the two reactivities of
      CDH was selectively knocked down by mutation experiments. CDH-H28A is much less
      able to catalyze the C?C bond formation, while the ability for C?C bond cleavage
      is still intact. The double variant CDH-H28A/N484A shows the opposite behavior
      and catalyzes the addition of pyruvate to cyclohexane-1,2-dione, resulting in the
      formation of a tertiary alcohol. Several acyloins of tertiary alcohols are formed
      with 54-94 % enantiomeric excess. In addition to pyruvate, methyl pyruvate and
      butane-2,3-dione are alternative donor substrates for C?C bond formation. Thus,
      the very rare aldehyde-ketone cross-benzoin reaction has been solved by design of
      an enzyme variant. 

PMID- 25382419
TI  - Development of an instrument for assessment of Korean nurses' attitudes toward
      obese patients.
AB  - AIM: The purpose of this study was to verify the validity and reliability of an
      instrument and to identify nurses' attitudes toward obese patients. METHODS:
      Basic questions were developed after a preliminary published work review, and
      content validity was verified by a group of experts. Principle components
      analysis was applied to the verified questions as a factor analysis, and a
      confirmatory factor analysis was used to verify whether each question qualified
      for a specific factor and construct reliability. Average variances were extracted
      and checked to appraise the reliability of each factor. RESULTS: The first 74
      questions composed with reference to the published work to identify nurses'
      attitudes toward obese patients were tested for construct validity and modified
      via factor analysis to 32 questions. Then, the questions were again modified to
      29 questions with four factors after a confirmatory factor analysis. Construct
      reliability and the average variance extracted for the factors were verified to
      demonstrate that this tool was highly reliable to explain the 29 factors under
      the four categories. CONCLUSION: These results show nurses' attitudes toward
      obese patients. Further research using various subject groups and appropriate
      measures is needed.

PMID- 25382420
TI  - Robustness of the division symmetry in Escherichia coli and functional
      consequences of symmetry breaking.
AB  - The morphological symmetry of the division process of Escherichia coli is well
      known. Recent studies verified that, in optimal growth conditions, most divisions
      are symmetric, although there are exceptions. We investigate whether such
      morphological asymmetries in division introduce functional asymmetries between
      sister cells, and assess the robustness of the symmetry in division to mild
      chemical stresses and sub-optimal temperatures. First, we show that the
      difference in size between daughter cells at birth is positively correlated to
      the difference between the numbers of fluorescent protein complexes inherited
      from the parent cell. Next, we show that the degree of symmetry in division
      observed in optimal conditions is robust to mild acidic shift and to mild
      oxidative stress, but not to sub-optimal temperatures, in that the variance of
      the difference between the sizes of sister cells at birth is minimized at 37 
      degrees C. This increased variance affects the functionality of the cells in
      that, at sub-optimal temperatures, larger/smaller cells arising from asymmetric
      divisions exhibit faster/slower division times than the mean population division
      time, respectively. On the other hand, cells dividing faster do not do so at the
      cost of morphological symmetry in division. Finally we show that at suboptimal
      temperatures the mean distance between the nucleoids increases, explaining the
      increased variance in division. We conclude that the functionality of E. coli
      cells is not immune to morphological asymmetries at birth, and that the
      effectiveness of the mechanism responsible for ensuring the symmetry in division
      weakens at sub-optimal temperatures. 

PMID- 25382421
TI  - C F Louis Leipoldt (1880-1947): Controversial paediatrician and prolific writer
      who cared passionately about the health of children.

PMID- 25382422
TI  - Allergic fungal sinusitis eroding the pterygoid plates: a rare case series.

PMID- 25382423
TI  - Headache induced by the sphenoid sinus mucocele.

PMID- 25382424
TI  - Assessment of mucosal changes associated with nasal splint in a rabbit model.
AB  - INTRODUCTION: There is no consensus on duration of the nasal splint after nasal
      septum surgeries. The pressure of nasal splint on the mucosa may cause tissue
      necrosis and nasal septum perforation. OBJECTIVES: To investigate the
      histopathological changes of the nasal mucosa caused by nasal splints in a rabbit
      model. METHODS: No splint was used in group A. Bilateral silicone nasal splints
      were placed for five, ten, and 15 days in groups B, C, and D, respectively.
      Biopsy of the nasal mucosa was performed after removal of splint. Histopathologic
      evaluations were performed. The severity and depth of the inflammation were
      scored. RESULTS: Group A had a normal histological appearance. Comparison of the
      results of groups B, C, and D with group A demonstrated statistically significant
      differences with regards to the severity of histopathological findings. There was
      no statistically significant difference between groups B and C. There were
      statistically significant differences between the groups B and D, and also
      between groups C and D. CONCLUSIONS: Longer duration of nasal splint had a higher
      risk for septal perforation. Therefore, removal of the splint as soon as possible
      may be helpful for preventing potential perforations.

PMID- 25382425
TI  - Postural control assessment in students with normal hearing and sensorineural
      hearing loss.
AB  - INTRODUCTION: Children with sensorineural hearing loss can present with
      instabilities in postural control, possibly as a consequence of hypoactivity of
      their vestibular system due to internal ear injury. OBJECTIVE: To assess postural
      control stability in students with normal hearing (i.e., listeners) and with
      sensorineural hearing loss, and to compare data between groups, considering
      gender and age. METHODS: This cross-sectional study evaluated the postural
      control of 96 students, 48 listeners and 48 with sensorineural hearing loss, aged
      between 7 and 18 years, of both genders, through the Balance Error Scoring
      Systems scale. This tool assesses postural control in two sensory conditions:
      stable surface and unstable surface. For statistical data analysis between
      groups, the Wilcoxon test for paired samples was used. RESULTS: Students with
      hearing loss showed more instability in postural control than those with normal
      hearing, with significant differences between groups (stable surface, unstable
      surface) (p<0.001). CONCLUSIONS: Students with sensorineural hearing loss showed
      greater instability in the postural control compared to normal hearing students
      of the same gender and age.

PMID- 25382426
TI  - Hearing health network: a spatial analysis.
AB  - INTRODUCTION: In order to meet the demands of the patient population with hearing
      impairment, the Hearing Health Care Network was created, consisting of primary
      care actions of medium and high complexity. Spatial analysis through
      geoprocessing is a way to understand the organization of such services.
      OBJECTIVE: To analyze the organization of the Hearing Health Care Network of the
      State of Minas Gerais. METHODS: Cross-sectional analytical study using
      geoprocessing techniques. The absolute frequency and the frequency per 1000
      inhabitants of the following variables were analyzed: assessment and diagnosis,
      selection and adaptation of hearing aids, follow-up, and speech therapy. The
      spatial analysis unit was the health micro-region. RESULTS: The assessment and
      diagnosis, selection, and adaptation of hearing aids and follow-up had a higher
      absolute number in the micro-regions with hearing health services. The follow-up
      procedure showed the lowest occurrence. Speech therapy showed higher occurrence
      in the state, both in absolute numbers, as well as per population. CONCLUSION:
      The use of geoprocessing techniques allowed the identification of the care flow
      as a function of the procedure performance frequency, population concentration,
      and territory distribution. All procedures offered by the Hearing Health Care
      Network are performed for users of all micro-regions of the state.

PMID- 25382427
TI  - Clinical characteristics of patients with persistent postural-perceptual
      dizziness.
AB  - INTRODUCTION: Persistent postural-perceptual dizziness is the dizziness that
      lasts for over three months with no clinical explanation for its persistence. The
      patient's motor response pattern presents changes and most patients manifest
      significant anxiety. OBJECTIVE: To evaluate the clinical characteristics of
      patients with persistent postural and perceptual dizziness. METHODS: statistical
      analysis of clinical aspects of patients with persistent postural-perceptual
      dizziness. RESULTS: 81 patients, average age: 50.06+/-12.16 years; female/male
      ratio: 5.7/1; main reasons for dizziness: visual stimuli (74%), body movements
      (52%), and sleep deprivation (38%). The most prevalent comorbidities were
      hypercholesterolemia (31%), migraine headaches (26%), carbohydrate metabolism
      disorders (22%) and cervical syndrome (21%). DHI, State-Trait Anxiety Inventory -
      Trait, Beck Depression Inventory, and Hospital Anxiety and Depression Scale
      questionnaires were statistically different (p<0.05) when compared to controls.
      68% demonstrated clinical improvement after treatment with serotonin reuptake
      inhibitors. CONCLUSION: Persistent postural-perceptual dizziness affects more
      women than men, with a high associated prevalence of metabolic disorders and
      migraine. Questionnaires help to identify the predisposition to persistent
      postural-perceptual dizziness. The prognosis is good with adequate treatment.

PMID- 25382428
TI  - Open fitting: performance verification of receiver in the ear and receiver in the
      aid.
AB  - OBJECTIVE: To verify the receiver in the ear and receiver in the aid adaptations
      by measuring in situ the speech perception and users' level of satisfaction.
      METHODS: The study was approved by the research ethics committee (Process:
      027/2011). Twenty subjects older than 18 years with audiological diagnosis of
      mild and moderate bilateral descending sensorineural hearing loss were evaluated.
      The subjects were divided into two groups, where G1 (group 1) was fitted with
      open-fit hearing aids with the built-in receiver unit (receiver in the ear) and
      G2 (group 2) was fitted with open-fit hearing aids with RITE. A probe microphone
      measurement was performed to check the gain and output provided by the
      amplification and for assessment of speech perception with Hearing in Noise Test
      with and without hearing aids. After a period of six weeks of use without
      interruption, the subjects returned for follow-up and answered the Satisfaction
      with Amplification in Daily Life questionnaire, and were again subjected to
      Hearing in Noise Test. RESULTS: Both groups presented better test results for
      speech recognition in the presence of noise. CONCLUSION: Groups 1 and 2 were
      satisfied with the use of hearing aids and improved speech recognition in silent
      and noisy situations with hearing aids.

PMID- 25382429
TI  - Reproducibility (test-retest) of vestibular evoked myogenic potential.
AB  - INTRODUCTION: There is still no consensus in the literature as to the best
      acoustic stimulus for capturing vestibular evoked myogenic potential (VEMP). Low
      frequency tone bursts are generally more effective than high-frequency, but
      recent studies still use clicks. Reproducibility is an important analytical
      parameter to observe the reliability of responses. OBJECTIVE: To determine the
      reproducibility of p13 and n23 latency and amplitude of the VEMP for stimuli with
      different tone-burst frequencies, and to define the best test frequency. METHODS:
      Cross-sectional cohort study. VEMP was captured in 156 ears, on the
      sternocleidomastoid muscle, using 100 tone-burst stimuli at frequencies of 250,
      500, 1000, and 2000Hz, and sound intensity of 95dB nHL. Responses were
      replicated, that is, recorded three times on each side. RESULTS: No significant
      difference was observed for p13 and n23 latencies of the VEMP, captured at three
      moments with tone-burst stimuli at 250, 500, and 1000Hz. Only the frequency of
      2000Hz showed a difference between captures of this potential (p<0.001). p13 and
      n23 amplitude analysis was also similar in the test-retest for all frequencies
      analyzed. CONCLUSION: p13 and n23 latencies and amplitudes of VEMP for tone-burst
      stimuli at frequencies of 250, 500, and 1000Hz are reproducible.

PMID- 25382430
TI  - Selective inhibitors of zinc-dependent histone deacetylases. Therapeutic targets
      relevant to cancer.
AB  - Histone deacetylases (HDACs), which act on acetylated histones and/or other non
      histone protein substrates, represent validated epigenetic targets for the
      treatment of cancer and other human diseases. The inhibition of HDAC activity was
      shown to induce cell cycle arrest, differentiation, apoptosis as well as a
      decrease in proliferation, angiogenesis, migration, and cell resistance to
      chemotherapy. Targeting single HDAC isoforms with selective inhibitors will help
      to reveal the role of individual HDACs in cancer development or uncover further
      biological consequences of protein acetylation. This review focuses on
      conventional zinc-containing HDACs. In its first part, the biological role of
      individual HDACs in various types of cancer is summarized. In the second part,
      promising HDAC inhibitors showing activity both in enzymatic and cell-based
      assays are surveyed with an emphasis on the inhibitors selective to the
      individual HDACs. 

PMID- 25382431
TI  - Retracted: why fish oil fails: a comprehensive 21st century lipids-based
      physiologic analysis.
AB  - [This retracts the article DOI: 10.1155/2014/495761.]. 

PMID- 25382432
TI  - Molecular dynamics simulations of complex mixtures aimed at the preparation of
      naproxen-imprinted xerogels.
AB  - The main objective of this study was to simulate for the first time a complex sol
      gel system aimed at preparing the (S)-naproxen-imprinted xerogel with an explicit
      representation of all the ionic species at pH 9. For this purpose, a series of
      molecular dynamics (MD) simulations of different mixtures, including species
      never studied before using the OPLS-AA force field, were prepared. A new
      parametrization for these species was developed and found to be acceptable. Three
      different systems were simulated, representing two types of pregelification
      models: the first one represented the initial mixture after complete hydrolysis
      and condensation to cyclic trimers (model A); the second one corresponded to the
      same mixture after the evaporation process (model B); and the last one was a
      simpler initial mixture without an explicit representation of all of the
      imprinting-mixture constituents (model C). The comparison of systems A and C
      mainly served the purpose of evaluating whether an explicit representation of all
      of the components (model A) was needed or if a less computationally demanding
      system in which the alkaline forms of the silicate species were ignored (model C)
      would be sufficient. The results confirmed our hypothesis that an explicit
      representation of all of the imprinting-mixture constituents is essential to
      study the molecular imprinting process because a poor representation of the ionic
      species present in the mixture may lead to erroneous conclusions or lost
      information. In general, the radial distribution function (RDF) analysis and
      interaction energies demonstrated a high affinity of the template molecule, 2-(6
      methoxynaphthalen-2-yl)propanoate (NAP(-), the conjugate base of (S)-naproxen),
      for the gel backbone, especially targeting the units containing the
      dihydroimidazolium moiety used as a functional group. Model B, representing a
      nearly gelled sol where the density of silicates and solvent polarity were much
      higher relative to the other models, allowed for much faster simulations. That
      gave us the chance to observe the templating effect through a comparative
      analysis and observation of the trajectories from simulations with the template-
      versus non-template-containing mixtures. Overall, a strong coherence between the
      imprinting-relevant interactions, aggregation, or the silicate network texturing
      effects taken out of the simulations and the experimentally high imprinting
      performance and porosity features of the corresponding gels was achieved. 

PMID- 25382433
TI  - Assessing the Adherence to Guidelines of Media Reporting of Suicide Using a Novel
      Instrument--the "Risk of Imitative Suicide Scale" (RISc).
AB  - Media guidelines for reporting of suicide are considered important in suicide
      prevention because of the risk of "imitative" suicide. There are currently no
      established tools for the quantification of quality of reporting. We sought to
      develop and validate a quality assessment instrument-the Risk of Imitative
      Suicide Scale (RISc). The RISc appears capable of discriminating reliably between
      adherent and nonadherent articles. Our data suggest that adherence to guidelines
      is inconsistent, and there are major differences between web-based and print
      media. The RISc could be used to evaluate effectiveness and consistency of media
      engagement with suicide prevention strategies. 

PMID- 25382434
TI  - Efficacy and side effects of radiation therapy in comparison with radiation
      therapy and temozolomide in the treatment of measurable canine malignant
      melanoma.
AB  - Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and
      therapeutic approaches remain largely palliative. A bi-institutional trial was
      conducted to compare efficacy and safety of radiation therapy (RT) and RT with
      post-radiation temozolomide in dogs with chemotherapy-naive, measurable MM. RT
      consisted of 5 * 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to
      pursue chemotherapy received adjuvant oral temozolomide (60 mg m-2 for 5 days
      every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs
      subsequently received temozolomide (Group 2). Overall response rate was similar
      between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was
      significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p =
      0.046). Survival time was not significantly different between groups. Both
      treatments were well tolerated. Post-radiation temozolomide has a good safety
      profile, and may improve TTP in MM when compared to coarse fractionated RT.

PMID- 25382435
TI  - Elucidating the interaction of limonene with bovine serum albumin: a multi
      technique approach.
AB  - The interaction of Bovine Serum Albumin (BSA) with limonene has been studied by
      UV-visible spectroscopy, fluorescence spectroscopy and molecular docking, and its
      effects on protein conformation, topology and stability were determined by
      Circular Dichroism (CD), Dynamic Light Scattering (DLS) and Differential Scanning
      Calorimetry (DSC). A gradual decrease in Stern-Volmer quenching constants with
      the increase in temperature showed the static mode of fluorescence quenching. The
      obtained binding constant (Kb) was ~10(4) M(-1). The temperature dependent Kb,
      Gibbs free energy (DeltaG), enthalpy (DeltaH) and entropy (DeltaS) changes were
      calculated, which revealed that the reaction is spontaneous and exothermic. The
      UV-visible spectra showed a change in the peaks within the aromatic region
      indicating hydrophobic interactions with Trp, Tyr and Phe in the protein.
      Moreover, limonene induced an increase in alpha-helical contents probably on the
      cost of random coils or/and beta-sheets of BSA, as observed from the far-UV CD
      spectra. The topology of BSA in the presence of limonene was slightly altered, as
      obtained from DLS results. The stability was also enhanced as revealed through
      thermal denaturation study by DSC and CD. Molecular docking study depicted that
      limonene fits into the hydrophobic pocket close to Sudlow site I in domain IIA of
      BSA. The present study will be helpful in understanding the binding mechanism of
      limonene and associated stability and conformational changes. 

PMID- 25382436
TI  - Prostate cancer survivors' beliefs about screening and treatment decision-making
      experiences in an era of controversy.
AB  - OBJECTIVE: Controversy about the costs and benefits of screening and treatment of
      prostate cancer (PCa) has recently intensified. However, the impact of the debate
      on PCa patients has not been systematically studied. METHODS: We assessed
      knowledge of, and attitudes toward, the U.S. Preventive Services Task Force's
      (USPSTF) May 2012 recommendation against PSA-based screening among men diagnosed
      with clinically localized PCa, and tested whether exposure to the recommendation
      and associated controversy about overtreatment of PCa predicted treatment
      decisional conflict, affected treatment choice, or increased regret about PSA
      testing. RESULTS: Accurate knowledge of the USPSTF recommendation was uncommon
      (19.1%). Attitudes toward the recommendation were negative, and the vast majority
      (86.5%) remained highly supportive of annual PSA testing in men >=50. Although
      exposure to the recommendation and controversy about treatment was associated
      with lower enthusiasm for screening and treatment, it was not associated with
      treatment decisions, or greater decisional-conflict, or regret. CONCLUSIONS:
      Findings may alleviate concern that exposure to PSA-based screening and
      overtreatment controversies has adversely affected recent cohorts of PCa
      patients. However, patients remain highly supportive of PSA-based screening. As
      survivor anecdotes often influence people's medical decisions, it is important to
      appreciate the scale of opposition to the new recommendation.

PMID- 25382437
TI  - The ascidian pigmented sensory organs: structures and developmental programs.
AB  - The recent advances on ascidian pigment sensory organ development and function
      represent a fascinating platform to get insight on the basic programs of chordate
      eye formation. This review aims to summarize current knowledge, at the structural
      and molecular levels, on the two main building blocks of ascidian light sensory
      organ, i.e. pigment cells and photoreceptor cells. The unique features of these
      structures (e.g., simplicity and well characterized cell lineage) are indeed
      making it possible to dissect the developmental programs at single cell
      resolution and will soon provide a panel of molecular tools to be exploited for a
      deep developmental and comparative-evolutionary analysis.

PMID- 25382438
TI  - Being sensitive to the signs and symptoms of depression.

PMID- 25382439
TI  - Local immune compartments are related to the severity of dextran sodium sulphate
      induced colitis.
AB  - Dextran sodium sulphate (DSS) induced colitis is commonly used to simulate human
      ulcerative colitis (UC). However, the mucosal immune responses related to the
      severity of disease have not been comprehensively documented. We used different
      concentration of DSS, induced various severities of colitis, and simultaneously
      examined the frequency of immune cells, antibodies and cytokine production. We
      found that T regulatory cells (Tregs), B cells, and IgA secretion increased on
      the recovery phase of mild colitis, accompanied by CD11b(+) cells, interleukin
      (IL)-6 and tumor necrosis factor (TNF)-alpha accumulated mildly. While during
      severe and irreversible colitis, the CD11b(+) cells, IL-6, and TNF-alpha
      infiltrated severely with Tregs, B cells, and IgA increased inconspicuously.
      These results demonstrate that Tregs, B cells, and IgA may play a significant
      role in maintaining the homeostasis of gut, by suppressing CD11b(+) cells and the
      pro-inflammatory cytokines.

PMID- 25382440
TI  - Involvement of the central monoaminergic system in the antidepressant-like effect
      of catalpol in mice.
AB  - Catalpol is a natural iridoid glycoside with diverse bioactivities that is found
      in abundance in Rehmannia glutinosa Libosch. (Scrophulariaceae). The present
      study assessed whether catalpol treatment (5, 10, or 20 mg/kg for 14 days by
      intragastric administration (i.g.)) has an antidepressant-like effect on mice
      performing the forced swim test (FST), tail suspension test (TST), open field
      test (OFT), and tests for reversal of reserpine-induced ptosis, akinesia, and
      hypothermia. This study also examined the potential role that catalpol plays in
      the cerebral monoaminergic system. Results indicated that catalpol administration
      produced an antidepressant-like effect in mice, as indicated by the reduced
      duration of immobility in the FST and TST, but it had no effect on locomotor
      activity in the OFT. Catalpol treatment significantly counteracted the decrease
      in rectal temperature, akinesia, and eyelid ptosis induced by reserpine.
      Moreover, catalpol increased levels of serotonin (5-HT) and its metabolite 5
      hydroxyindoleacetic acid (5-HIAA) in the brains of mice, but it did not affect
      levels of norepinephrine (NE) or dopamine (DA). These antidepressant-like effects
      of catalpol are essentially similar to the effects of the clinical antidepressant
      fluoxetine hydrochloride (FH). This is the first study to indicate that catalpol
      has an antidepressant-like effect and that its action may be mediated by the
      central serotonergic system, and not by noradrenergic or dopaminergic systems.

PMID- 25382441
TI  - Protection of Angelica sinensis (Oliv) Diels against hepatotoxicity induced by
      Dioscorea bulbifera L. and its mechanism.
AB  - Dioscorea bulbifera L., a traditionally used medicinal plant in China, is
      reported to induce hepatotoxicity. The present study is designed to investigate
      the protection of an ethanol extract of Angelica sinensis (Oliv) Diels (AE)
      against an ethyl acetate fraction of D. bulbifera (EF)-induced liver injury and
      its engaged mechanism. High performance liquid chromatography (HPLC) analysis
      showed that the amount of diosbulbin B in EF was 16.03% and ferulic acid in AE
      was 0.18%. EF (350 mg/kg) increased serum alanine/aspartate aminotransferase
      (ALT/AST), alkaline phosphatase (ALP) activities and total bilirubin (TB) amount,
      while AE inhibited such an increase. Liver histological evaluation showed that AE
      prevented development of severe hepatic lesions induced by EF. Further results
      showed that EF decreased the expression of Bcl-2 and induced the cleaved
      activation of caspase-9 and -3, and all those effects were reversed by AE. AE
      also reversed EF-induced decreased expression of the inhibitor of kappa B
      (IkappaB), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Taken
      together, our results demonstrate that AE can prevent EF-induced hepatotoxicity
      via preventing apoptosis, meanwhile IkappaB, SOD, and GPx may be involved in such
      protection.

PMID- 25382442
TI  - Fabrication and bioactivity evaluation of porous anodised TiO2 films in vitro.
AB  - This study aims to find an optimal method for modifying the neck of dental
      implants for gingival attachment through in vitro investigations of the
      biological features of various anodised TiO2 films. The titanium sheets were
      divided into four groups: a control group and three test groups classified
      according to the anodisation voltage (Group 150 V, Group 180 V or Group 200
      V).The surface microstructure and crystal structure were observed using scanning
      electron microscopy and X-ray diffraction. The protein adsorption ability,
      antibacterial activity and cell adhesion ability were tested to examine the
      biological properties of the materials in vitro. Microscopic grooves were
      observed in the control group, whereas the test groups contained numerous pores.
      Group 180 V and Group 200 V showed higher protein adsorption ability (p < 0.05),
      whereas Group 150 V and Group 180 V exhibited better antibacterial activity (p <
      0.05). Higher cell concentrations of L929 were observed in Group 180V and Group
      200 V than in the other two groups (p < 0.05), which indicated that the TiO2
      films formed at 180 V promote protein adsorption and enhance fibroblast growth
      while inhibiting bacterial adhesion. These results indicate that anodisation
      positively affects the formation of a biological seal in the neck region of
      dental implants.

PMID- 25382443
TI  - Clinical utility of simultaneous measurement of alpha-fetoprotein and des-gamma
      carboxy prothrombin for diagnosis of patients with hepatocellular carcinoma in
      China: A multi-center case-controlled study of 1,153 subjects.
AB  - This study aimed to investigate the clinical utility of simultaneous measurement
      of alphafetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) for
      hepatocellular carcinoma (HCC) diagnosis in Chinese patients predominantly caused
      by hepatitis B virus infection by a multi-center case-controlled study. Subjects
      were 1,153 individuals from three major hospitals in China, including 550 cases
      in HCC group, 164 in Malignant disease group, 182 in Benign disease group, 85 in
      Chronic liver disease group, and 173 in Normal group. Serum levels of AFP and DCP
      were measured and clinicopathological features were determined for all subjects.
      Results showed that the levels of DCP and AFP were significantly higher in HCC
      group (550 patients, 74.18% with HBV infection) than that in other four groups (P
      < 0.001). Receiver operating curves (ROC) indicated the optimal cut-off value was
      86 mAU/mL for DCP with a sensitivity of 71.50% and specificity of 86.30%, and 21
      ng/mL for AFP with a sensitivity of 68.00% and specificity of 93.20%. The area
      under ROC curve was 0.846 for DCP, 0.832 for AFP, and 0.890 for the combination
      of DCP and AFP. The combination of DCP and AFP resulted in a higher Youden index
      and a sensitivity of approximately 90%, even for small tumors. The simultaneous
      measurement of AFP and DCP could achieve a better sensitivity in diagnosing
      Chinese HCC patients, even for small tumors.

PMID- 25382444
TI  - Relationship between renal apparent diffusion coefficient values and glomerular
      filtration rate in infants with congenital hydronephrosis.
AB  - The aim was to investigate the relationship between apparent diffusion
      coefficient (ADC) values measured by diffusion-weighted magnetic resonance
      imaging (DW MRI) and the split glomerular filtration rate (GFR) in infants with
      congenital hydronephrosis. Diffusion-weighted imaging (DWI) (b = 0 and 700
      seconds/mm(2)) was performed with a General Electric Company (GE) Signa 1.5T MR
      unit in 46 infants suffering single congenital hydronephrosis and in 30 healthy
      infants as normal control group. The ADCs were calculated with regions of
      interest (ROIs) positioned in the renal parenchyma. The 46 obstructed kidneys
      were classified into four groups according to the GFR level: renal dysfunction
      compensated group, renal dysfunction decompensated group, renal failure group,
      and uremia group. The renal ADCs in six groups (normal kidneys in control group,
      contralateral kidneys, and four groups of hydronephrotic kidneys) were compared
      statistically using analysis of variance (ANOVA), and the correlative
      relationship between ADCs and GFR was examined by Pearson's correlation test.
      There were statistically significant differences in renal ADCs among the six
      groups. The ADCs of hydronephrotic kidneys were lower than that of the normal
      kidneys. There was a moderate positive correlation between the ADCs of
      hydronephrotic kidneys and split GFR (r = 0.744). This study indicated that the
      ADCs of congenital hydronephrotic kidneys were lower than that of normal renal
      parenchyma, and there was a positive correlation between the ADCs and split renal
      GFR, which demonstrates that the ADCs can reflect the filtration function of
      hydronephrotic kidneys and may provide some reference to help clinical physician
      to explore a novel noninvasive approach to evaluate the single renal function.

PMID- 25382445
TI  - Use of a mini-instrument in endoscopic thyroidectomy via a breast approach to
      improve cosmetic outcomes.
AB  - The objective of this research was to evaluate the clinical benefits of using a
      mini-instrument during endoscopic thyroidectomy via a breast approach (ETBA).
      Surgery-related indices and cosmetic results were compared for 20 patients
      underwent ETBA with a mini-instrument (ETBA-m) and 20 patients who underwent
      standard ETBA (sETBA). Patients were closely matched in terms of age, gender,
      tumor size, and pathology. Patients who underwent sETBA had a significantly
      larger area of dissection and total length of incisions compared to patients who
      underwent ETBA-m (136.25 +/- 19.22 cm(2)vs. 105.25 +/- 9.54 cm(2), p < 0.001 and
      2.66 +/- 0.09 cm vs. 2.08 +/- 0.24 cm, p < 0.001). All patients who underwent
      ETBA-m commented that they preferred their current cosmetic appearance after they
      were shown a picture of the scars of a patient who underwent sETBA. Results of
      this study revealed that use of a mini-instrument in ETBA is technically safe and
      feasible and it offers improved cosmetic outcomes compared to sETBA.

PMID- 25382446
TI  - Revisiting Einstein's brain in Brain Awareness Week.
AB  - Albert Einstein's brain has long been an object of fascination to both
      neuroscience specialists and the general public. However, without records of
      advanced neuro-imaging of his brain, conclusions regarding Einstein's
      extraordinary cognitive capabilities can only be drawn based on the unique
      external features of his brain and through comparison of the external features
      with those of other human brain samples. The recent discovery of 14 previously
      unpublished photographs of Einstein's brain taken at unconventional angles by Dr.
      Thomas Stoltz Harvey, the pathologist, ignited a renewed frenzy about clues to
      explain Einstein's genius. Dr. Dean Falk and her colleagues, in their landmark
      paper published in Brain (2013; 136:1304-1327), described in such details about
      the unusual features of Einstein's brain, which shed new light on Einstein's
      intelligence. In this article, we ask what are the unique structures of his
      brain? What can we learn from this new information? Can we really explain his
      extraordinary cognitive capabilities based on these unique brain structures? We
      conclude that studying the brain of a remarkable person like Albert Einstein
      indeed provides us a better example to comprehensively appreciate the
      relationship between brain structures and advanced cognitive functions. However,
      caution must be exercised so as not to over-interpret his intelligence solely
      based on the understanding of the surface structures of his brain.

PMID- 25382447
TI  - Neuropsychological profile of a male psychiatric patient with a Morgagni-Stewart
      Morel syndrome.
AB  - In 1765 Giovanni Morgagni described a syndrome consisting of hyperostosis
      frontalis interna (HFI), obesity and hirsutism. In 1928 Stewart and in 1930 Morel
      added neuropsychiatric symptoms, e.g. depression and dementia, which led to the
      definition of the Morgagni-Stewart-Morel Syndrome (MSM). Although mostly women
      were characterized in literature no gender specifity is demanded. This case
      report presents the rare case of a 66 year old male psychiatric patient with
      Morgagni-Stewart-Morel Syndrome. The patient complained of loss of concentration
      and difficulties with activities of daily living. Admission diagnosis was an
      opioid misuse on the basis of a chronic pain syndrome. In this case report we are
      describing clinical features, the patient history and technical (MRI) and
      neuropsychological tests. Although severe psychiatric symptoms and
      neuropsychological deficits are commonly seen in these patients, our patient
      showed only mild symptoms. This case reports shows the possibility of a male
      patient with MSM. If MSM is a separate entity or just an epiphenomena of hormone
      dysregulation should be investigated in further studies. 

PMID- 25382448
TI  - Randomized controlled trial on the efficacy of new alcohol-free chlorhexidine
      mouthrinses after 8 weeks.
AB  - OBJECTIVES: To evaluate the efficacy of two alcohol-free antimicrobial
      mouthrinses in reducing plaque and gingivitis compared to an alcohol-containing
      rinse and toothbrushing alone. METHODS: One hundred and sixty healthy volunteers
      were enrolled in the randomized controlled trial. Participants were randomly and
      equally assigned to four groups: (i) toothbrushing + rinsing (0.06% CHX + 0.025%
      NaF, alcohol-containing rinse, positive control); (ii) toothbrushing + rinsing
      (0.06% CHX + 0.025% NaF, alcohol-free experimental rinse); (iii) toothbrushing +
      rinsing (0.06% CHX + 0.03% CPC + 0.025% NaF, alcohol-free experimental rinse);
      (iv) toothbrushing alone (negative control). At baseline, Quigley-Hein plaque
      index (QHI), modified proximal plaque index (MPPI), and papillary bleeding index
      (PBI) were recorded. All subjects brushed their teeth as usual during the study.
      Additionally, groups 1-3 rinsed twice daily. Eight weeks after baseline, indices
      were recorded again. anova with Bonferroni adjustment served for statistical
      analysis. RESULTS: One hundred and fifty-five participants were included into
      final analysis (i: n = 39, 2: n = 39, 3: n = 37, 4: n = 40). Experimental rinses
      (ii, iii) reduced QHI and MPPI to a higher extent than the negative control (iv),
      whereas no significant difference to the positive control was found. QHI: (i)
      36.6%, (ii) 32.3%, (iii) 36.8%, (iv) 21.6%; MPPI: (i) 11.9%, (ii) 12.2%, (iii)
      13.6%, (iv) 3.5%. For PBI, no statistically significant difference was found
      between groups: (i) 80.2%, (ii) 77.8%, (iii) 76.5% and (iv) 78.8%. CONCLUSIONS:
      With respect to QHI and MPPI, toothbrushing in combination with any rinse was
      more effective than toothbrushing alone. No statistically significant differences
      were found between the alcohol-free and the alcohol-containing control rinses.

PMID- 25382449
TI  - Low gravity rotational culture and the integration of immunomodulatory stem cells
      reduce human islet allo-reactivity.
AB  - Modification of human islets prior to transplantation may improve long-term
      clinical outcome in terms of diabetes management, by supporting graft function
      and reducing the potential for allo-rejection. Intragraft incorporation of stem
      cells secreting beta (beta)-cell trophic and immunomodulatory factors represents
      a credible approach, but requires suitable culture methods to facilitate islet
      alteration without compromising integrity. This study employed a three
      dimensional rotational cell culture system (RCCS) to achieve modification,
      preserve function, and ultimately influence immune cell responsiveness to human
      islets. Islets underwent intentional dispersal and rotational culture-assisted
      aggregation with amniotic epithelial cells (AEC) exhibiting intrinsic
      immunomodulatory potential. Reassembled islet constructs were assessed for
      functional integrity, and their ability to induce an allo-response in discrete T
      cell subsets determined using mixed islet:lymphocyte reaction assays. RCCS
      supported the formation of islet:AEC aggregates with improved insulin secretory
      capacity compared to unmodified islets. Further, the allo-response of peripheral
      blood mononuclear cell (PBMC) and purified CD4+ and CD8+ T-cell subsets to AEC
      bearing grafts was significantly (p < 0.05) attenuated. Rotational culture
      enables pre-transplant islet modification involving their integration with
      immunomodulatory stem cells capable of subduing the allo-reactivity of T cells
      relevant to islet rejection. The approach may play a role in achieving acute and
      long-term graft survival in islet transplantation. 

PMID- 25382450
TI  - Tracking of body size from birth to 7 years of age and factors associated with
      maintenance of a high body size from birth to 7 years of age--the Norwegian
      Mother and Child Cohort study (MoBa).
AB  - OBJECTIVE: To examine tracking of body size among children participating in the
      Norwegian Mother and Child Cohort Study (MoBa) from birth to 7 years of age and
      additionally to explore child and parental characteristics associated with
      maintenance of a high body size in this period of life. DESIGN: Anthropometric
      data at birth and at 1, 3 and 7 years of age were collected by questionnaires
      addressed to the mother. SETTING: Participants were recruited from all over
      Norway during the period 1999-2008. SUBJECTS: A total of 3771 children had
      complete anthropometric data at birth and at 1, 3 and 7 years of age; the sample
      includes children born between 2002 and 2004. RESULTS: Cohen's weighted kappa
      pointed to fair (0.36) to moderate (0.43) tracking of body size from birth to 7
      years of age. Generalized estimating equations further indicated that children in
      the highest tertile of ponderal index at birth had nearly one unit higher BMI
      (kg/m(2)) at the age of 7 years compared with children in other tertiles of
      ponderal index at birth. Having parents with high BMI (>= 25.0 kg/m(2)) increased
      the odds of having a stable high body size from birth to 7 years of age;
      moreover, girls had significantly higher odds compared with boys. CONCLUSIONS:
      The study indicates fair to moderate tracking of body size from birth to 7 years
      of age. From a public health perspective, early prevention of childhood
      overweight and obesity seems to be especially important among children of parents
      having a high BMI.

PMID- 25382451
TI  - Neuro-cognitive performance of very preterm or very low birth weight adults at 26
      years.
AB  - BACKGROUND: Children born very preterm (VP <32 weeks gestation) and/or with very
      low birth weight (VBLW <1500 g; subsequently VP/VLBW) have been previously
      reported to have more cognitive impairment and specific executive functioning
      problems than term children; however, it remains unclear whether these problems
      persist into adulthood. This study aimed to examine general intelligence (IQ) and
      executive functioning (EF) of adults born VP/VLBW in comparison to term controls.
      Additionally, the effects of smallness for gestational age (SGA) and family
      socioeconomic status (SES) at birth were investigated. METHODS: The Bavarian
      Longitudinal Study is a geographically defined prospective cohort study of
      neonatal at-risk children born in 1985/86 in Southern Germany. A total of 217
      VP/VLBW and 197 controls completed the battery of IQ and EF tests at 26 years of
      age. RESULTS: VP/VLBW adults scored significantly lower than controls in IQ and
      EF. There was a 1.16 standard deviation (SD) unit difference between the VP/VLBW
      and controls in Full-Scale IQ. VP/VLBW adults were found to have general and
      multiple cognitive problems rather than specific deficits in EF. SGA was not a
      significant predictor of cognitive impairment. Family SES had a significant
      impact on general intelligence in both VP/VLBW and term controls. The SES effects
      amounted to 1.13 SD units between individuals born into high versus low SES.
      CONCLUSIONS: No narrowing of cognitive deficits between VP/VLBW and term control
      adults to previous childhood assessments at 6 years of age was found. VP/VLBW
      adults do not outgrow their cognitive problems despite many receiving special
      educational support in childhood. Low family SES at birth has similar additive
      adverse effects on cognitive performance in VP/VLBW and term offspring.

PMID- 25382453
TI  - Carp edema virus/Koi sleepy disease: an emerging disease in Central-East Europe.
AB  - Koi sleepy disease (KSD), also known as carp edema virus (CEV), was first
      reported from juvenile colour carp in Japan in the 1970s. Recently, this pox
      virus was detected in several European countries, including Germany, France and
      the Netherlands. In England, in addition to colour carp, outbreaks in common carp
      are reported. KSD/CEV is an emerging infectious disease characterized by a
      typical sleepy behaviour, enophthalmia, generalized oedematous condition and gill
      necrosis, leading to hypoxia. High mortality, of up to 80-100%, is seen in
      juvenile koi collected from infected ponds. In Austria, this disease had not been
      detected until now. In spring 2014, diagnostic work revealed the disease in two
      unrelated cases. In one instance, a pond with adult koi was affected; in the
      other, the disease was diagnosed in adult common carp recently imported from the
      Czech Republic. A survey was carried out on recent cases (2013/2014), chosen from
      those with similar anamnestic and physical examination findings, revealing a
      total of 5/22 cases positive for KSD/CEV. In this study, two paradigmatic cases
      are presented in detail. Results together with molecular evidence shaped the
      pattern of the first diagnosis of KSD/CEV in fish from Austrian ponds. In the
      light of the positive cases detected from archived material, and the spread of
      the disease through live stock, imported from a neighbouring country, the need
      for epidemiological investigations in Austria and surrounding countries is
      emphasized. 

PMID- 25382452
TI  - The rationale and design of the Beta-blocker to LOwer CArdiovascular Dialysis
      Events (BLOCADE) Feasibility Study.
AB  - AIMS: The Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE)
      Feasibility Study aims to determine the feasibility of a large-scale randomized
      controlled trial with clinical endpoints comparing the beta-blocking agent
      carvedilol with placebo in patients receiving dialysis. METHODS: The BLOCADE
      Feasibility Study is a randomized, double-blind, placebo-controlled, parallel
      group feasibility study comparing the beta-blocking agent carvedilol with
      placebo. Patients receiving dialysis for >=3 months and who are aged >=50 years,
      or who are >=18 years and have diabetes or cardiovascular disease, were eligible.
      The primary outcome was the proportion of participants who complete a 6-week run
      in phase in which all participants received carvedilol titrated from 3.125 mg
      twice daily to 6.25 mg twice daily. Other measures included how many patients are
      screened, the proportion recruited, the overall recruitment rate, the proportion
      of participants who remain on study drug for 12 months and the incidence of intra
      dialytic hypotension while on randomized treatment. RESULTS: The BLOCADE
      Feasibility Study commenced recruiting in May 2011 and involves 11 sites in
      Australia and New Zealand. CONCLUSIONS: The BLOCADE Feasibility Study will inform
      the design of a larger clinical endpoint study to determine whether beta-blocking
      agents provide benefit to patients receiving dialysis, and define whether such a
      study is feasible.

PMID- 25382454
TI  - Fetal outcome after prenatal exposure to chemotherapy and mechanisms of
      teratogenicity compared to alcohol and smoking.
AB  - INTRODUCTION: The treatment of cancer during pregnancy is challenging because of
      the involvement of two individuals and the necessity of a multidisciplinary
      approach. An important concern is the potential impact of chemotherapy on the
      developing fetus. AREAS COVERED: The authors review the available literature on
      neonatal and long-term outcome of children prenatally exposed to chemotherapy.
      Chemotherapy administered during first trimester of pregnancy results in
      increased congenital malformations (7.5 - 17% compared to 4.1 - 6.9% background
      risk), whereas normal rates are found during second or third trimester.
      Intrauterine growth restriction is seen in 7 - 21% (compared to 10%), but
      children develop normal weight and height on the long term. Children are born
      preterm in 67.1%, compared to 4% in general population. Normal intelligence,
      attention, memory and behavior are reported, although intelligence tends to
      decrease with prematurity. Global heart function remains normal, although small
      differences are seen in ejection fraction, fractional shortening and some
      diastolic parameters. No secondary cancers or fertility problems are encountered,
      but follow up periods are limited. EXPERT OPINION: Most evidence is based on
      retrospective studies with small samples and limited follow up periods,
      methodology and lack of control groups. A large prospective case-control study
      with long-term follow up is needed in which confounding factors are well
      considered.

PMID- 25382455
TI  - Temperature variable luminescence and color tuning of Eu2+/Mn2+-codoped strontium
      magnesium phosphates as promising red-emitting phosphors for light emitting
      diodes.
AB  - Eu(2+) and Mn(2+) codoped violet-/red-emitting strontium magnesium phosphates,
      SrMgP2O7, SrMg2P2O8 and Sr2Mg3P4O15, were prepared and their emission properties,
      especially for color tuning with temperature variable luminescence, were
      investigated. Simply by changing the host composition of the SrO-MgO-P2O5 ternary
      system, we can control the Eu(2+)-sensitized Mn(2+) emission efficiency as well
      as the thermal quenching of incorporated activators. We can realize that the
      overall luminescence behavior is induced by the Mn(2+) center positioned at
      different coordination states with intermixed Sr(2+)/Mg(2+) sites in various
      hosts, which resulted in widely tunable colors from violet-red through orange-red
      to pure red. Finally, bright and stable reddish color illuminated light emitting
      diodes (LEDs) can be obtained by combining the proposed phosphates with
      ultraviolet LEDs, demonstrating the potential red-emitting phosphors for
      ultraviolet-pumped phosphor converted white-LEDs. 

PMID- 25382457
TI  - A combined "electrochemical-frustrated lewis pair" approach to hydrogen
      activation: surface catalytic effects at platinum electrodes.
AB  - Herein, we extend our "combined electrochemical-frustrated Lewis pair" approach
      to include Pt electrode surfaces for the first time. We found that the
      voltammetric response of an electrochemical-frustrated Lewis pair (FLP) system
      involving the B(C6 F5 )3 /[HB(C6 F5 )3 ](-) redox couple exhibits a strong
      surface electrocatalytic effect at Pt electrodes. Using a combination of kinetic
      competition studies in the presence of a H atom scavenger, 6-bromohexene, and by
      changing the steric bulk of the Lewis acid borane catalyst from B(C6 F5 )3 to
      B(C6 Cl5 )3 , the mechanism of electrochemical-FLP reactions on Pt surfaces was
      shown to be dominated by hydrogen-atom transfer (HAT) between Pt, [Pt?H] adatoms
      and transient [HB(C6 F5 )3 ](?) electrooxidation intermediates. These findings
      provide further insight into this new area of combining electrochemical and FLP
      reactions, and proffers additional avenues for exploration beyond energy
      generation, such as in electrosynthesis. 

PMID- 25382458
TI  - Effect of photoperiod on slow and fast developing individuals in aphidophagous
      ladybirds, Menochilus sexmaculatus and Propylea dissecta (Coleoptera:
      Coccinellidae).
AB  - The effects of environmental parameters on insect development have been studied
      extensively. But the reasons for 2 differential developmental rates within same
      cohort under varying environmental factors have not been explored. For the
      purpose, in this study the existence and stability of slow and fast development
      under 5 photoperiods (i.e., 8L: 16D, 10L : 14D, 12L : 12D, 14L : 10D and 16L :
      8D; light and dark hours per day) and its effect on body mass and reproductive
      attributes in 2 aphidophagous ladybirds, Menochilus sexmaculatus (Fabricius) and
      Propylea dissecta (Mulsant) was examined on Aphis craccivora Koch at 27 +/- 1 
      degrees C temperature. A clear bimodal (2 peaks, where the first peak represented
      the fast developing and the 2nd peak slow developing individuals) pattern of
      distribution at each photoperiod was found. The proportion of slow and fast
      developing individuals in a cohort differed with photoperiods. The slow
      developing individuals were more in numbers at 8L : 16D, in equal numbers at 14L
      : 10D and in less numbers at 16L: 8D, indicating that the variation in emergence
      was owing to exogenous cues influenced differential rates of mortality. Slow
      developing individuals had female biased sex ratio, higher longevity and lower
      body mass than fast developing individuals. Fast developing females laid higher
      numbers of eggs with higher egg viability than slow developing females. Study of
      such variations in development at different photoperiods is helpful to understand
      its role in the development of insects particularly ladybirds and permits the
      selection of fast developing bioagents for their use in biocontrol of pest
      species. 

PMID- 25382456
TI  - Exploring the transfer of recent plant photosynthates to soil microbes:
      mycorrhizal pathway vs direct root exudation.
AB  - Plants rapidly release photoassimilated carbon (C) to the soil via direct root
      exudation and associated mycorrhizal fungi, with both pathways promoting plant
      nutrient availability. This study aimed to explore these pathways from the root's
      vascular bundle to soil microbial communities. Using nanoscale secondary ion mass
      spectrometry (NanoSIMS) imaging and (13) C-phospho- and neutral lipid fatty
      acids, we traced in-situ flows of recently photoassimilated C of (13) CO2 
      exposed wheat (Triticum aestivum) through arbuscular mycorrhiza (AM) into root-
      and hyphae-associated soil microbial communities. Intraradical hyphae of AM fungi
      were significantly (13) C-enriched compared to other root-cortex areas after 8 h
      of labelling. Immature fine root areas close to the root tip, where AM features
      were absent, showed signs of passive C loss and co-location of photoassimilates
      with nitrogen taken up from the soil solution. A significant and exclusively
      fresh proportion of (13) C-photosynthates was delivered through the AM pathway
      and was utilised by different microbial groups compared to C directly released by
      roots. Our results indicate that a major release of recent photosynthates into
      soil leave plant roots via AM intraradical hyphae already upstream of passive
      root exudations. AM fungi may act as a rapid hub for translocating fresh plant C
      to soil microbes.

PMID- 25382460
TI  - Effect of Infliximab in oxidised serum albumin levels during experimental
      colitis.
AB  - Infliximab (IFX) is widely used in ulcerative colitis and in Crohn's disease
      treatment. Both diseases are characterised by increased oxidative stress, which
      may affect albumin oxidation. In order to test this hypothesis, the effect of IFX
      on colitis induced by dextran sulphate sodium (DSS) in rats was evaluated by
      measuring the Disease Activity Index, biochemical parameters, serum albumin
      oxidation and colonic mucosa oxidation. Rats with colitis showed an increase in
      oxidised serum albumin levels and in the oxidation of colon mucous cells. Both
      decreased after IFX treatment. This suggests that oxidised albumin could be a
      useful biomarker for monitoring inflammatory bowel disease.

PMID- 25382459
TI  - MR elastography and diffusion-weighted imaging of ex vivo prostate cancer:
      quantitative comparison to histopathology.
AB  - The purpose of this work was (1) to develop a magnetic resonance elastography
      (MRE) system for imaging of the ex vivo human prostate and (2) to assess the
      diagnostic power of mono-frequency and multi-frequency MRE and diffusion weighted
      imaging (DWI) alone and combined as correlated with histopathology in a patient
      study. An electromagnetic driver was designed specifically for MRE studies in
      small-bore MR scanners. Ex vivo prostate specimens (post-fixation) of 14 patients
      who underwent radical prostatectomy were imaged with MRE at 7 T (nine cases had
      DWI). In six patients, the MRE examination was performed at three frequencies
      (600, 800, 1000 Hz) to extract the power-law exponent Gamma. The images were
      registered to wholemount pathology slides marked with the Gleason score. The
      areas under the receiver-operator-characteristic curves (AUC) were calculated.
      The methods were validated in a phantom study and it was demonstrated that (i)
      the driver does not interfere with the acquisition process and (ii) the driver
      can generate amplitudes greater than 100 um for frequencies less than 1 kHz. In
      the quantitative study, cancerous tissue with Gleason score at least 3 + 3 was
      distinguished from normal tissue in the peripheral zone (PZ) with an average AUC
      of 0.75 (Gd ), 0.75 (Gl ), 0.70 (Gamma-Gd ), 0.68 (apparent diffusion
      coefficient, ADC), and 0.82 (Gd  + Gl  + ADC). The differentiation between PZ and
      central gland was modest for Gd (p < 0.07), Gl (p < 0.06) but not significant for
      Gamma (p < 0.2). A correlation of 0.4 kPa/h was found between the fixation time
      of the prostate specimen and the stiffness of the tissue, which could affect the
      diagnostic power results. DWI and MRE may provide complementary information; in
      fact MRE performed better than ADC in distinguishing normal from cancerous tissue
      in some cases. Multi-frequency (Gamma) analysis did not appear to improve the
      results. However, in light of the effect of tissue fixation, the clinical
      implication of our results may be inconclusive and more experiments are needed.

PMID- 25382464
TI  - Communication through molecular bridges: different bridge orbital trends result
      in common property trends.
AB  - Common trends in communication through molecular bridges are ubiquitous in
      chemistry, such as the frequently observed exponential decay of
      conductance/electron transport and of exchange spin coupling with increasing
      bridge length, or the increased communication through a bridge upon closing a
      diarylethene photoswitch. For antiferromagnetically coupled diradicals in which
      two equivalent spin centers are connected by a closed-shell bridge, the molecular
      orbitals (MOs) whose energy splitting dominates the coupling strength are similar
      in shape to the MOs of the dithiolated bridges, which in turn can be used to
      rationalize conductance. Therefore, it appears reasonable to expect the observed
      common property trends to result from common orbital trends. We illustrate based
      on a set of model compounds that this assumption is not true, and that common
      property trends result from either different pairs of orbitals being involved, or
      from orbital energies not being the dominant contribution to property trends. For
      substituent effects, an effective modification of the pi system can make a
      comparison difficult.

PMID- 25382465
TI  - Study of vitellogenin in Boophilus annulatus tick larvae and its immunological
      aspects.
AB  - Boophilus annulatus is an important one-host tick in the Mediterranean regions
      and Iran. It can transmit the Babesia bigemina, Babesia bovis and Anaplasma
      marginale to cattle. Nowadays, immunization programs by tick proteins is one of
      the potential methods for the control and prevention of tick infestations.
      Therefore, the characterization and identification of various tick proteins are
      necessary. Vitellogenin is a precursor of vitellin that is produced in mid gut
      cells and fat bodies in ticks. In this study, we characterized vitellogenin
      protein of B. annulatus unfed larvae using one- and two-dimensional
      electrophoresis and immunoblotting. In one-dimensional immunoblotting, 48, 70,
      100, 130 and >250 kDa protein bands positively reacted with immune sera. In two
      dimensional immunoblotting many protein spots positively reacted with immune
      sera. Six of them were analyzed by MALDI-TOF and MALDI-TOF- TOF mass
      spectrometry. The results showed that amino acid sequences of four immunogenic
      proteins with molecular weights of 38, 43, 85 and 97 kDa had identity to tick
      vitellogenin and its homologues (GP80), based on the Mascot search results. It
      seems that more knowledge on tick proteins including vitellogenin and their
      characterization could be useful for the development of anti-tick vaccines. 

PMID- 25382466
TI  - Molecular and seroepidemiological survey of Babesia bovis and Babesia bigemina
      infections in cattle and water buffaloes in the central region of Vietnam.
AB  - In the present study, a total of 137 blood samples were collected from cattle and
      water buffaloes in central region of Vietnam and tested using nested polymerase
      chain reaction (nPCR), enzyme-linked immunosorbent assay (ELISA) and indirect
      fluorescent antibody test (IFAT) to determine the molecular and serological
      prevalence of Babesia bovis and Babesia bigemina. In cattle, the prevalence of B.
      bovis and B. bigemina was 21.3% and 16.0% by nPCR, 73.4% and 42.6% by ELISA and
      60.6% and 59.6% by IFAT, respectively, whereas those of water buffalos were 23.3%
      and 0% by nPCR, 37.2% and 9.3% by ELISA and 27.9% and 18.6% by IFAT,
      respectively. IFAT and ELISA detected a higher number of infected cattle and
      water buffaloes than nPCR totally. Statistically significant differences in the
      prevalence of the two infections were observed on the basis of age. Overall, the
      current data suggest high incidence of B. bovis and B. bigemina infections in the
      central region of Vietnam, which is needed to develop comprehensive approach to
      the modern surveillance, diagnosis and control of bovine babesiosis. 

PMID- 25382467
TI  - Acaricidal activity of Ocimum basilicum and Spilanthes acmella against the
      ectoparasitic tick, Rhipicephalus (Boophilus) microplus (Arachinida: Ixodidae).
AB  - The ectoparasitic tick, Rhipicephalus (Boophilus) microplus collected at various
      cattle farms in and around Chennai was subjected to treatment of different crude
      solvent extracts of leaves of Ocimum basilicum and Spilanthes acmella for
      acaricidal activity. Among various solvent extracts of leaves of O. basilicum and
      S. acmella used, chloroform extract of O. basilicum at concentrations between 6%
      and 10% exhibited 70% and 100% mortality of ticks when compared to control. The
      LC50 and LC90 values of the chloroform extract of leaves of O. basilicum
      treatment on the ticks after 24 h were observed as 5.46% and 7.69%. Quantitative
      and qualitative analysis of alpha- and beta- carboxylesterase enzymes in the
      whole gut homogenate of cattle tick, R. microplus treated with chloroform extract
      of leaves of O. basilicum revealed higher level of activities for the enzymes.
      This indicated that there was an induced response in the tick, R. microplus
      against the toxic effects of the extract of O. basilicum. 

PMID- 25382468
TI  - Comparison between Quantitative Buffy Coat (QBC) and Giemsa-stained Thin Film
      (GTF) technique for blood protozoan infections in wild rats.
AB  - The quantitative buffy coat (QBC) technique and conventional Giemsa thin blood
      smear was compared to determine the sensitivity and specificity of the technique
      in detecting blood parasitic infection of the rodent populations from four urban
      cities in Peninsular Malaysia. A total of 432 blood samples from four rat species
      (Rattus norvegicus, Rattus rattus diardii, Rattus exulans and Rattus
      argentiventer) were screened using both techniques and successfully detected two
      blood protozoan species (Trypanosoma lewisi and Plasmodium sp.) with Trypanosoma
      lewisi predominantly infecting the population. Results showed that Giemsa-stained
      thin film (GTF) was the better detection method on blood parasitemia (46.7%)
      compared to Quantitative Buffy Coat method (38.9%) with overall detection
      technique sensitivity and specificity at 83.2% and 74.8% respectively. The
      sensitivity in detection of Trypanosoma lewisi was 84.4% with value slightly
      lower for Plasmodium sp. infections at 76.6%. Statistical analysis proved that
      GTF technique was significantly more sensitive in the detection of blood
      protozoan infections in the rodent population compared to QBC (p<0.05). 

PMID- 25382469
TI  - Seroprevalence of Anaplasma phagocytophilum in well maintained horses from
      northern Tunisia.
AB  - The aim of the present study was to determine the seroprevalence of Anaplasma
      phagocytophilum in 343 well maintained horses belonging to 11 horse stables
      located in northern Tunisia with indirect immunofluorescence test. Overall, 16.3%
      (56/343) of tested animals were positive. Anti-A. phagocytophilum antibodies were
      present in horses located in all studied governorates except the governorate of
      Ben Arous. Nine horse stables out of 11 contained positive animals, the
      seroprevalence of each one varied from nought to 50%. Seroprevalence varied
      according to gender, breed and type of activity, contrary to age. Seroprevalence
      was higher in females than males (21.4 and 9.5% respectively). Similarly,
      seropositive animals belonging to the English thoroughbred breed was
      significantly higher (30.2%) than other breeds. According to the utilization of
      horses, the highest positivity rate (21.1%) was observed in brood mares. Our
      results demonstrate that A. phagocytophilum infection is widespread in well
      maintained horses from northern Tunisia, so equine granulocytic anaplasmosis
      should be suspected by veterinarians in front of suggestive clinical signs like
      fever, ataxia and reluctance to move. 

PMID- 25382470
TI  - Surveillance and resistance status of Aedes population in two suburban
      residential areas in Kampar town, Perak, Malaysia.
AB  - In this study, 13 weeks (October to December 2012) of ovitrap surveillance was
      conducted in two suburban residential areas in Kampar town, Perak. A total of
      17,310 Aedes mosquitoes were found in Taman Kampar Jaya, whereas Taman Juloong
      recorded a higher number at 19,042. Less than 1% of these were identified as
      Aedes aegypti, with the remaining confirmed as Aedes albopictus. The female Ae.
      albopictus were subsequently subjected to WHO standard diagnostic test kits
      against two pyrethroids (0.05% deltamethrin and 0.75% permethrin) and two
      organophosphates (1% fenitrothion and 5% malathion). The Ae. albopictus from both
      research sites were the most susceptible to deltamethrin, recording KT50 and KT95
      response values of 15.84 minutes and 16.18 minutes; and 48.18 minutes and 49.44
      minutes respectively. This was followed by permethrin (20.57 minutes and 17.52
      minutes; 29.54 minutes and 54.54 minutes) and malathion (48.46 minutes and 62.69
      minutes; 87.72 minutes and 141.04 minutes). Fenitrothion was found to be least
      effective towards Ae. albopictus; recording KT50 and KT95 response values of
      150.29 minutes and 293.41 minutes for Taman Kampar Jaya, and 203.32 minutes and
      408.07 minutes respectively for Taman Juloong. All tested Ae. albopictus showed
      100% mortality after 24 hours post exposure. As both residential areas were
      fogged periodically by the municipal council; alternating between
      organophosphates and pyrethroids, thus, constant monitoring is crucial in light
      of the emergence of resistance noted in Ae. albopictus towards fenitrothion. 

PMID- 25382471
TI  - Acaricidal effects of fenvalerate and cypermethrin against Rhipicephalus
      (Boophilus) annulatus.
AB  - The acaricidal effects of two most commonly used acaricides viz., fenvalerate and
      cypermethrin against Rhipicephalus (Boophilus) annulatus were studied using Adult
      Immersion Test (AIT). The LC50 values observed for fenvalerate and cypermethrin
      were 1570 ppm and 184 ppm respectively. The death of ticks was not an immediate
      process. Fenvalerate caused death only after 7 days while cypermethrin after 5
      days of treatment. The eggs laid by treated ticks did not hatch at all
      concentrations tested. 

PMID- 25382472
TI  - Oviposition deterring and oviciding potentials of Ipomoea cairica L. leaf extract
      against dengue vectors.
AB  - Bioprospecting of plant-based insecticides for vector control has become an area
      of interest within the last two decades. Due to drawbacks of chemical
      insecticides, phytochemicals of plant origin with mosquito control potential are
      being utilized as alternative sources in integrated vector control. In this
      regard, the present study aimed to investigate oviposition deterring and
      oviciding potentials of Ipomoea cairica (L.) (Family: Convolvulaceae) crude leaf
      extract against dengue vectors, Aedes aegypti and Aedes albopictus. Ipomoea
      cairica is an indigenous plant that has demonstrated marked toxicity towards
      larvae of Ae. aegypti and Ae. albopictus. Leaves of I. cairica were extracted
      using Soxhlet apparatus with acetone as solvent. Oviposition deterrent activity
      and ovicidal assay was carried out in oviposition site choice tests with three
      different concentrations (50, 100, 450 ppm). Acetone extract of I. cairica leaf
      strongly inhibited oviposition with 100% repellence to Ae. aegypti at lower
      concentration of 100 ppm, while for Ae. albopictus was at 450 ppm. The
      oviposition activity index (OAI) values which ranged from -0.69 to -1.00 revealed
      that I. cairica demonstrated deterrent effect. In ovicidal assay, similar trend
      was observed whereby zero hatchability was recorded for Ae. aegypti and Ae.
      albopictus eggs at 100 and 450 ppm, respectively. It is noteworthy that I.
      cairica leaf extract had significantly elicited dual properties as oviposition
      deterrent and oviciding agent in both Aedes species. Reduction in egg number
      through oviposition deterring activity, reduction in hatching percentage and
      survival rates, suggested an additional hallmark of this plant to be integrated
      in Aedes mosquito control. Ipomoea cairica deserved to be considered as one of
      the potential alternative sources for the new development of novel plant based
      insecticides in future. 

PMID- 25382473
TI  - Assessment of residual bio-efficacy and persistence of Ipomoea cairica plant
      extract against Culex quinquefasciatus Say mosquito.
AB  - Specification on residual action of a possible alternative insecticide derived
      from plant materials is important to determine minimum interval time between
      applications and the environmental persistence of the biopesticides. The
      objective of this study is to evaluate crude acethonilic extract of Ipomoea
      cairica leaves for its residual and persistence effects against Culex
      quinquefasciatus larvae. Wild strain of Cx. quinquefasciatus larvae were used for
      the purpose of the study. Two test designs, replenishment of water and without
      replenishment of water were carried out. For the first design, a total of 10 ml
      of test solution containing Ip. cairica extracts was replenished daily and
      replaced with 10 ml of distilled water. For the second design, treatment water
      was maintained at 1500 ml and only evaporated water was refilled. Larval
      mortality was recorded at 24 hours post-treatment after each introduction period
      and trials were terminated when mortality rate falls below 50%. Adult emergences
      from survived larvae were observed and number of survivals was recorded. For the
      non-replenishment design, mortality rate significantly reduced to below 50% after
      28 days, meanwhile for replenishment of water declined significantly after 21
      days (P < 0.05). There was no adult emergence observed up to seven days for non
      replenishment and first two days for replenishment of water design. The short
      period of residual effectiveness of crude acethonilic extract of Ip. cairica
      leaves with high percentage of larval mortality on the first few days, endorses
      fewer concerns of having excess residues in the environment which may carry the
      risk of insecticide resistance and environmental pollution.

PMID- 25382474
TI  - Infestation of Lernaeenicus seeri (Copepoda: Pennellidae) and Hirudinella
      ventricosa (Digenea: Hirudinellidae) on wahoo Acanthocybium solandri collected
      from Parangipettai, southeast coast of India.
AB  - A commercially important fish, wahoo Acanthocybium solandri (Cuvier, 1832)
      (Scombridae), was collected to study the infestation of parasites from
      Parangipettai landing center, Tamil Nadu, southeast coast of India for a period
      of one year from January to December 2011. A total of 644 fish were captured and
      screened for parasites. Off 644 fish, 270 were infested by a parasitic copepod
      Lernaeenicus seeri Kirtisinghe, 1934 (Siphonostomatoida: Pennellidae) on the body
      surface. It is a mesoparasite, since the head and neck are inserted and attached
      to the muscle by making a wound/hole on the body and the rest of the parasite
      body with the egg sacs hanging outside. Prevalence was recorded as 42.29% with
      mean and maximum intensity at 3.22 and 33, respectively. Seasonal study showed
      that the prevalence was highest (62.82 %) during postmonsoon. Simultaneously,
      some of the fish (n = 144) were internally observed for the presence of parasites
      and we found that 101 fish were infested with an endoparasite digenean
      Hirudinella ventricosa (Pallas, 1774) (Hirudinellidae) in the stomach. Prevalence
      was recorded as 70.9%, and mean intensity of 1.62 and maximum intensity of 3 were
      also noted. The overall percentage of both copepod and digenean infestation were
      recorded as 60.42%. The infestation was high in postmonsoon season for both
      parasites. This is the first record of L. seeri from Indian waters and the second
      record of occurrence worldwide. Significant interactions were observed between
      season and infestation of both parasites (P<0.05).

PMID- 25382475
TI  - The life-cycle of Spirometra species from Peninsular Malaysia.
AB  - The life-cycle of Malaysian Spirometra spp. was studied under experimental
      conditions in the laboratory. The Cyclops were reared as the first intermediate
      host, the hamster as the experimental second intermediate host and cat as the
      definitive host. Maturation and hatching of eggs took 6 to 12 days by incubation
      at temperature 30 oC. The hatched coracidium measured 46 x 34 MUm. The Cyclops
      used were susceptible to the coracidial infection. The procercoid older than 5
      days in the Cyclop body cavity had minute spines at the anterior end, calcium
      corpuscles in the body parenchyma and the cercomer at the posterior end.
      Procercoids 10 to 14 days old were infective to hamster. The plerocercoids from
      the hamster after 30 days were long and slender and were infective to cats. The
      plerocercoids experimentally inoculated to cats developed to adult worms and
      began to produce eggs between 10 to 60 days. Based on the results that have been
      obtained, a complete life-cycle was successfully elucidated in the laboratory and
      hamster was identified to be a good laboratory model for a second intermediate
      host of Spirometra sp.

PMID- 25382476
TI  - Aural myiasis caused by Parasarcophaga (Liosarcophaga) dux (Thomson) in Thailand.
AB  - Herein is reported the first case in Thailand of aural myiasis caused by the
      flesh fly, Parasarcophaga (Liosarcophaga) dux (Thomson). A 5-day-old infant was
      taken to hospital with a slightly bloody ear. Two fly larvae exiting the ear and
      another recovered by a physician were alive, and confirmed as P. dux species from
      adult examination results. This case brought attention to the need for protection
      against synanthropic flies, particularly for infants and/or hearing impaired
      patients. 

PMID- 25382477
TI  - Intestinal parasitic diarrhea among children in Baghdad--Iraq.
AB  - Parasitic diarrhea among children is a significant health problem worldwide. This
      cross sectional study described the burden of parasitic diarrhea among children.
      The objectives of this study were to evaluate the impact of risk factors on the
      parasitic diarrhea, and to determine the parasitic profile among children in
      Baghdad-Iraq, during the period extending from September 2003 to June 2004. A
      total number of 2033 cases were included in the study. The estimated prevalence
      rate of parasitic diarrhea was 22%. We identified the following major diarrhea
      determinants were large households size, residential location, water source, low
      socioeconomic status, and low parent education. Giardia lamblia was found to be
      the most prevalent parasite with an infection rate of 45.54% followed by
      Entamoeba histolytica 23.44%, Enterobius vermicularis 12.7%, Hymenolepis nana
      9.82%, Trichuris trichiura 5.4%, and Ascaris lumbricoides 2.2%. In conclusion,
      this study demonstrates that poor sanitation, inadequate environmental
      conditions, and low socioeconomic status are the main determining factors that
      predispose children to parasitic diarrhea. Mass deworming programs are
      recommended for school children, as this population is easily accessible. 

PMID- 25382478
TI  - Comparison of three diagnostic methods for the detection of Toxoplasma gondii in
      free range chickens.
AB  - Detection of Toxoplasma gondii in free range chickens is an indicator of the
      prevalence and distribution pattern of T. gondii in the environment. For this
      purpose, serologic assays especially modified agglutination test (MAT) is the
      main approach in the literature. The main goal of this study was to compare the
      polymerase chain reaction (PCR) based on amplification of first internal
      transcribed spacer (ITS-1) of ribosomal DNA gene, ELISA, and MAT to demonstrate
      T. gondii infection in free range chicken. A total of 106 adult free - range
      chickens were killed. Blood, whole heart and brain samples were taken. Sera were
      examined for the presence of T. gondii antibodies by ELISA and MAT as well.
      Selected tissues were used for PCR and bioassay in mice. The results revealed
      that 48.11%, 51.89%, 46.23% and 27.36% of chickens were positive in ELISA, MAT,
      PCR and bioassay in mice respectively. Good correlation between the results of
      PCR, ELISA and MAT were detected, but not with bioassay in mice. Compared with
      PCR, the sensitivity and specificity of ELISA were 92.16% and 96.36% respectively
      and also for MAT, the sensitivity was 81.81% and the specificity was 92.15%. The
      specific diagnosis of T. gondii infection in chickens is central to a better
      understanding of the epidemiology and dynamics of transmission among the various
      host population and is particularly important for planning effective optimal
      prevention and control programs. Our data in the present study demonstrated that
      PCR, ELISA and the MAT are helpful and precise methods to detect T. gondii in
      naturally infected free-range chickens. 

PMID- 25382479
TI  - Novel parasitic nematode-specific protein of bovine filarial parasite Setaria
      digitata displays conserved gene structure and ubiquitous expression.
AB  - Setaria digitata is an animal filarial parasite, which can cause fatal diseases
      to livestock such as cattle, sheep, goat, buffaloes, horses etc. inflicting
      considerable economic losses to livelihood of livestock farmers. In spite of
      this, the biology and parasitic nature of this organism is largely unknown. As a
      step towards understanding these, we screened the cDNA library of S. digitata and
      identified an open reading frame that code for parasitic nematode-specific
      protein, which showed a significant homology to functionally and structurally
      unannotated sequences of parasitic nematodes Wuchereria bancrofti, Brugia malayi,
      Onchocerca volvulus, Loa loa etc., suggesting its role in parasitism. RT-PCR
      analysis indicated that the S. digitata novel gene (SDNP) is expressed in adult
      female and male, and microfilariae. Southern hybridization studies revealed that
      this gene is a single-copy gene. Sequence analysis of the genomic region obtained
      from overlapping PCR amplification indicated that the size of the genomic region
      is 1819 bp in which four exons encoding 205 amino acids were interrupted by three
      introns of varying lengths of 419, 659 and 123 bp, and also the expansion of the
      size of the introns of S. digitata compared to its orthologues by integrating
      micro and mini-satellite containing sequence. Sequences around the splice
      junctions were conserved and agreed with the general GT-AG splicing rule. The
      gene was found to be AT rich with a GC content of 38.1%. Bioinformatic analysis
      indicated that the gene structure of SDNP and its orthologues is conserved and it
      expressed ubiqutously in all the stages of nematode's life cycle. Therefore,
      taking these outcomes together, it can be concluded that SDNP is a parasitic
      nematode-specific, single copy gene having conserved gene structure of four exons
      interrupted by three introns and that the gene is expressed ubiquitously
      throughout nematode's life cycle. 

PMID- 25382480
TI  - Incidence and risk factors of Giardia duodenalis infection in an orphanage,
      Thailand.
AB  - A cohort study was performed to evaluate the incidence and risk factors of
      Giardia duodenalis infection in an orphanage in suburban area outside Bangkok,
      central Thailand. Stool specimens were examined for the presence of G. duodenalis
      in January 2007, May 2007 and January 2008. Of 892 stool specimens from 481
      individuals, simple wet preparation, PBS ethyl-acetate sedimentation and PCR
      amplification of the SSU-rRNA gene were performed to detect G. duodenalis. Using
      PCR of the glutamate dehydrogenase gene and sequence analysis, G. duodenalis
      assemblages were identified. Associated risk factors were analysed using Fisher's
      exact test which revealed significant infection of G. duodenalis in boys and
      specific rooms where orphans aged 25-48 months old lived. Genotypic
      characterization of G. duodenalis revealed that assemblage A subtype AII was the
      most predominant found in orphans living in the specific rooms, thus the
      transmission was likely to occur via person-to-person. Other modes of
      transmission were less likely to occur. This study showed that the incidence rate
      of Giardia infection gradually decreased significantly after the implementation
      of health education and appropriate treatment of infected orphans. 

PMID- 25382481
TI  - Back to basic: bio-burden on hands of health care personnel in tertiary teaching
      hospital in Malaysia.
AB  - Hands of Health Care Personnel (HCP) are one of the most common vehicles for the
      transmission of infection. Microorganisms can survive well on the hands of HCP
      for a certain duration. Therefore, the purpose of this study is to bring
      awareness to HCP that their hands can actually be contaminated with many
      microorganisms. These microbes on the hands of HCP can potentially infect their
      patients if they do not comply with the proper hand hygiene practice. This cross
      sectional study was conducted at a randomly selected Intensive Care Unit (ICU)
      and general ward in a hospital. Twenty five HCP from each ward were randomly
      selected and their hands were imprinted on blood culture plates. Microorganism
      growth were quantified and identified. Data were analyzed and presented as
      descriptive analysis. One hundred blood agar plates were processed and analyzed.
      Majority (71%) of the samples had more than 50 colony-forming units (CFU) and
      only 17% of the samples had less than 25 CFU. Microorganisms identified include
      Staphylococcus spp., Acinetobacter spp., Enterobacteriaceae, Pseudomonas spp.,
      Moraxella, Delftiaacidovorans and fungi. All isolated microorganisms were
      antibiotic sensitive strain. This study showed that the hands of HCP were
      contaminated with many microorganisms. Therefore, it is imperative that HCP must
      practice proper hand hygiene when taking care of their patients in the wards. 

PMID- 25382482
TI  - Bacterial constituents of indoor air in a high throughput building in the
      tropics.
AB  - Airborne bacteria are significant biotic constituents of bioaerosol. Bacteria at
      high concentrations in the air can compromise indoor air quality (IAQ) and result
      in many diseases. In tropical environments like Malaysia that extensively utilize
      air-conditioning systems, this is particularly significant due to continuous
      recirculation of indoor air and the potential implications for human health.
      Currently, there is a lack of knowledge regarding the impact of airborne bacteria
      on IAQ in Malaysia. This study was prompted by a need for reliable baseline data
      on airborne bacteria in the indoor environment of tropical equatorial Malaysia,
      that may be used as a reference for further investigations on the potential role
      played by airborne bacteria as an agent of disease in this region. It was further
      necessitated due to the threat of bioterrorism with the potentiality of release
      of exotic pathogenic microorganisms into indoor or outdoor air. Before scientists
      can detect the latter, a gauge of the common microorganisms in indoor (as well as
      outdoor) air needs to be ascertained, hence the expediency of this study.
      Bacterial counts from the broad-based and targeted study were generally in the
      order of 10(2) colony-forming units (CFU) per m(3) of air. The most prevalent
      airborne bacteria found in the broad-based study that encompassed all five levels
      of the building were Gram-positive cocci (67.73%), followed by Gram-positive rods
      (24.26%) and Gram-negative rods (7.10%). Gram-negative cocci were rarely detected
      (0.71%). Amongst the genera identified, Kytococcus sp., Micrococcus sp.,
      Staphylococcus sp., Leifsonia sp., Bacillus sp. and Corynebacterium sp.
      predominated in indoor air. The most dominant bacterial species were Kytococcus
      sedentarius, Staphylococcus epidermidis and Micrococcus luteus. The opportunistic
      and nosocomial pathogen, Stenotrophomonas maltophilia was also discovered at a
      high percentage in the cafeteria. The bacteria isolated in this study have been
      increasingly documented to cause opportunistic infections in immuno-compromised
      patients, sometimes with fatal outcomes. Furthermore, some of them are becoming
      increasingly resistant to antibiotics. Hence, we propose that indoor reservoirs
      of these bacteria and their associated clinical and more subtle health effects,
      if any, be investigated further.

PMID- 25382483
TI  - Genotyping of chloroquine resistant Plasmodium falciparum in wild caught
      Anopheles minimus mosquitoes in a malaria endemic area of Assam, India.
AB  - We validated the feasibility of using Plasmodium falciparum, the human malaria
      parasite, DNA present in wild caught vector mosquitoes for the characterization
      of chloroquine resistance status. House frequenting mosquitoes belonging to
      Anopheles minimus complex were collected from human dwellings in a malaria
      endemic area of Assam, Northeast India and DNA was extracted from the head-thorax
      region of individual mosquitoes. Anopheles minimus complex mosquitoes were
      identified to species level and screened for the presence of Plasmodium sp. using
      molecular tools. Nested PCR-RFLP method was used for genotyping of P. falciparum
      based on K76T mutation in the chloroquine resistance transporter (pfcrt) gene.
      Three of the 27 wild caught An. minimus mosquitoes were harbouring P. falciparum
      sporozoites (positivity 11.1%) and all 3 were had 76T mutation in the pfcrt gene,
      indicating chloroquine resistance. The approach of characterizing antimalarial
      resistance of malaria parasite in vector mosquitoes can potentially be used as a
      surveillance tool for monitoring transmission of antimalarial drug resistant
      parasite strains in the community. 

PMID- 25382484
TI  - Phylogenetic analysis of human metapneumovirus among children with acute
      respiratory infections in Kuala Lumpur, Malaysia.
AB  - Human metapneumovirus (HMPV) is a recently discovered cause of viral respiratory
      infections. We describe clinical and molecular epidemiology of HMPV cases
      diagnosed in children with respiratory infection at University of Malaya Medical
      Centre, Kuala Lumpur, Malaysia. The prevalence rate of HMPV between 2010 and 2012
      was 1.1%, and HMPV contributed 6.5% of confirmed viral respiratory infections.
      The HMPV patients had a median age of 1.6 years, and a median hospital admission
      of 4 days. The most common clinical presentations were fever, rhinitis,
      pneumonia, vomiting/diarrhoea, and bronchiolitis. Based on the partial sequences
      of F fusion gene from 26 HMPV strains, 14 (54%) were subgenotype A2b, which was
      predominant in 2010; 11 (42%) were subgenotype B1, which was predominant in 2012;
      and 1 (4%) was subgenotype A2a. Knowledge of the circulating subgenotypes in
      Malaysia, and the displacement of predominant subgenotypes within 3 years, is
      useful data for future vaccine planning. 

PMID- 25382485
TI  - Periodic current oscillation catalyzed by delta-MnO2 nanosheets.
AB  - The oxygen evolution reaction (OER) is of wide interest for both fuel and
      hydrometallurgy applications. Different types of nanoscale MnO2 , varying from
      nanosheets to nanoneedles, are synthesized and assembled on the anode to
      investigate their catalytic effect on the nonlinear kinetics of the MnO2 
      catalyzed OER at high current. For delta-MnO2 nanosheets, periodic current
      oscillations (PCO) occurr and occupy up to 40 % of the total energy consumption.
      The PCO can help to reduce the energy consumption under constant current
      conditions. Its amplitude could be twice of that for the previously reported MnO2
      grown by an in situ electrochemical method. If the amount of gamma-MnO2
      nanoneedles increases, the oscillation disappears. For different Mn oxides, the
      rate constants of H2 O2 decomposition differ, resulting in changes in oscillation
      features. The results of this study may enable new ideas to improve the
      efficiency of industrial electrolysis and charging-discharging of
      supercapacitors. 

PMID- 25382486
TI  - Reliable harvest of a dorsal scapular artery perforator flap by augmenting its
      perfusion.
AB  - Despite confirmation of a reliable perforasome in the dorsal scapular artery in
      an anatomic study, a true perforator flap has not been recommended in previous
      clinical studies because of concerns regarding insufficient perfusion in the
      distal region. In this report, we present two cases of reconstruction for
      occipital defects caused by tumor extirpation using pedicled dorsal scapular
      artery perforator flaps without a muscle component. To secure the perfusion of
      the dorsal scapular artery perforator flap, inclusion of an additional perforator
      was attempted for perfusion augmentation. The second dorsal scapular artery
      perforator was harvested in one case. In an additional case, the sixth dorsal
      intercostal artery perforator with a branch that directly connected with the
      dorsal scapular artery within the trapezius muscle was additionally harvested.
      The flaps survived without any perfusion-related complications, including tip
      necrosis, and no donor site morbidities were observed. We suggest that a
      perfusion augmented dorsal scapular artery perforator flap by harvesting multiple
      perforators could be a safe and useful alternative for reconstructive surgery of
      head and neck defects.

PMID- 25382487
TI  - Intrafamilial variability of ZRS-associated syndrome: characterization of a
      mosaic ZRS mutation by pyrosequencing.
AB  - During limb development, the spatio-temporal expression of sonic hedgehog (SHH)
      is driven by the Zone of polarizing activity Regulatory Sequence (ZRS), located 1
      megabase upstream from SHH. Gain-of-function mutations of this enhancer, which
      cause ectopic expression of SHH, are known to be responsible for congenital limb
      malformations with variable expressivity, ranging from preaxial polydactyly or
      triphalangeal thumbs to polysyndactyly, which may also be associated with
      mesomelic deficiency. In this report, we describe a patient affected with mirror
      image polydactyly of the four extremities and bilateral tibial deficiency. The
      proband's father had isolated preaxial polydactyly type II (PPD2). Using Sanger
      sequencing, a ZRS point mutation (NC_000007.14, g.156584153A>G, UCSC, Build
      hg.19) was only identified in the patient. However, pyrosequencing analysis
      enabled the detection of a 10% somatic mosaic in the blood and saliva from the
      father. To our knowledge, this is the first description of a ZRS mosaic mutation.
      This report highlights the complexity of genotype-phenotype correlation in ZRS
      associated syndromes and the importance of detecting somatic mosaicism for
      accurate genetic counselling. 

PMID- 25382488
TI  - Development and trunk segmentation of early instars of a ptychopariid trilobite
      from Cambrian Stage 5 of China.
AB  - Many three-dimensionally preserved exoskeletons found from the middle Cambrian
      (Stage 5) Gaotai Formation in Guizhou, southern China, have been assigned to the
      ptychopariid trilobite Gunnia sp. They represent mainly a series of early
      instars, exhibiting some delicate structures and morphological variation
      associated with their trunk segmentation and early development. Morphometric and
      statistical analyses indicate that the transverse joint appears to occur with the
      full growth of the third axial ring of the protopygidium, which increases in size
      much more rapidly than its corresponding protocephalon with growth. The 'one by
      one' sequential release of thoracic segments from a transitory pygidium does not
      progress exactly in accordance with the development of the pygidial axis, whose
      axial rings increase at a relatively faster rate, and an 'immature ring' always
      appears initially at the rear end of the axis. These new data set up a testable
      model for revealing trilobite segmentation and provide fresh insights into the
      development, evolution and taphonomic surroundings associated with the Cambrian
      trilobites. 

PMID- 25382489
TI  - In-line separation by capillary electrophoresis prior to analysis by top-down
      mass spectrometry enables sensitive characterization of protein complexes.
AB  - Intact protein analysis via top-down mass spectrometry (MS) provides a bird's eye
      view over the protein complexes and complex protein mixtures with the unique
      capability of characterizing protein variants, splice isoforms, and combinatorial
      post-translational modifications (PTMs). Here we applied capillary
      electrophoresis (CE) through a sheathless CE-electrospray ionization interface
      coupled to an LTQ Velos Orbitrap Elite mass spectrometer to analyze the Dam1
      complex from Saccharomyces cerevisiae. We achieved a 100-fold increase in
      sensitivity compared to a reversed-phase liquid chromatography coupled MS
      analysis of recombinant Dam1 complex with a total loading of 2.5 ng (12 amol). N
      terminal processing forms of individual subunits of the Dam1 complex were
      observed as well as their phosphorylation stoichiometry upon Mps1p kinase
      treatment. 

PMID- 25382490
TI  - Men's preferences and trade-offs for prostate cancer screening: a discrete choice
      experiment.
AB  - OBJECTIVES: Prostate cancer screening using prostate-specific antigen (PSA)
      remains controversial. In deciding about screening, men must weigh the benefits
      and harms: little is known about benefit: harm trade-offs men are willing to
      accept. The objective of this study was to assess men's preferences for PSA
      screening, and the trade-offs between benefits and harms men are willing to
      accept when deciding about screening. METHODS: Preferences of 662 men aged 40-69
      were assessed using a discrete choice experiment. PSA screening was described by
      six attributes: prostate cancer deaths, prostate cancer diagnoses, unnecessary
      biopsies from false-positive PSA tests, impotence, urinary incontinence/bowel
      problems and cost. A mixed logit model was used to examine the influence of
      attributes on men's preferences for PSA testing; benefit: harm trade-offs were
      also calculated. RESULTS: Men's preferences were significantly influenced by test
      characteristics, particularly potential mortality benefit, unnecessary biopsies
      and likelihood of urinary incontinence or bowel problems; preferences were also
      influenced by age, prior PSA testing experience and perceived risk of prostate
      cancer. Men were willing to accept between 65 and 233 of 10 000 extra men with
      unnecessary biopsies, and between 31 and 72 of 10 000 extra men with
      incontinence/bowel problems to avoid one prostate cancer death. CONCLUSIONS:
      Differences in valuations of attributes and trade-offs acceptable to men of
      different ages suggest a one size fits all approach to PSA testing, regardless of
      age, may not reflect men's preferences. Our results can be used by policymakers
      to ensure screening programmes are in line with men's preferences and by
      clinicians and patients to facilitate informed discussions of the most relevant
      benefits and downsides of PSA screening for an individual man.

PMID- 25382491
TI  - High-resolution nanotransfer printing applicable to diverse surfaces via
      interface-targeted adhesion switching.
AB  - Nanotransfer printing technology offers outstanding simplicity and throughput in
      the fabrication of transistors, metamaterials, epidermal sensors and other
      emerging devices. Nevertheless, the development of a large-area sub-50 nm
      nanotransfer printing process has been hindered by fundamental reliability issues
      in the replication of high-resolution templates and in the release of generated
      nanostructures. Here we present a solvent-assisted nanotransfer printing
      technique based on high-fidelity replication of sub-20 nm patterns using a dual
      functional bilayer polymer thin film. For uniform and fast release of
      nanostructures on diverse receiver surfaces, interface-specific adhesion control
      is realized by employing a polydimethylsiloxane gel pad as a solvent-emitting
      transfer medium, providing unusual printing capability even on biological
      surfaces such as human skin and fruit peels. Based on this principle, we also
      demonstrate reliable printing of high-density metallic nanostructures for non
      destructive and rapid surface-enhanced Raman spectroscopy analyses and for
      hydrogen detection sensors with excellent responsiveness. 

PMID- 25382492
TI  - Floral isolation is the major reproductive barrier between a pair of rewarding
      orchid sister species.
AB  - The crucial role of reproductive isolation in speciation has long been
      recognized; however, a limited number of studies quantify different isolation
      barriers and embed reproductive isolation in a phylogenetic context. In this
      study, we investigate reproductive isolation between the often sympatrically
      occurring orchid species, Gymnadenia conopsea and G. odoratissima. We examine the
      phylogenetic relationship between the two species and analyse floral isolation,
      fruit set and seed viability from interspecies crosses, as well as the ploidy
      level. Additionally, we quantify interspecies differences in floral signals and
      morphology. The results suggest that the two species have a sister-species
      relationship. In terms of reproductive isolation, we found complete floral
      isolation between the two species, but little to no post-pollination isolation;
      the species also mostly had the same ploidy level in the studied populations. We
      also show clear distinctions in floral signals, as well as in floral size and
      spur length. We propose that respective adaptation to short- vs. long-tongued
      pollinators was the driver of speciation in the here studied Gymnadenia species.
      Our study supports the key role of floral isolation in orchid speciation and
      shows that floral isolation is not restricted to highly specialized pollination
      systems, but can also occur between species with less specialized pollination. 

PMID- 25382495
TI  - Strengthening the systemic ties that bind: integrating common factors into
      marriage and family therapy curricula.
AB  - Specific models guide the training of marriage and family therapists (MFTs) as
      they offer both structure and organization for both therapists and clients.
      Learning models may also benefit therapists-in-training by instilling confidence
      and preventing atheoretical eclecticism. The moderate common factors perspective
      argues that models are essential, but should not be taught as "the absolute
      truth," given there is no evidence for relative efficacy of one empirically
      validated model versus another, and no single model works in all instances. The
      following article provides a blueprint for infusing a common factors perspective
      into MFT programmes by reviewing innovations in course design, outlining specific
      teaching strategies, and highlighting potential implementation challenges. 

PMID- 25382494
TI  - The role of FDG-PET/CT in the evaluation of residual disease in paediatric non
      Hodgkin lymphoma.
AB  - (18) F-labelled-fluorodeoxyglucose positron emission tomography (FDG-PET)
      findings are challenging to interpret for residual disease versus complete
      response in paediatric patients with non-Hodgkin lymphoma (NHL). A biopsy is
      often warranted to confirm the presence or absence of viable tumour if there is
      clinical or radiographic evidence of residual disease. In this study, we compared
      conventional imaging and FDG-PET/computerized tomography (CT) findings with
      biopsy results in 18 children with NHL. Our goal was to provide additional data
      to establish more reliable criteria for response evaluation. Residual disease was
      suspected after conventional imaging alone in eight patients, after FDG-PET/CT
      alone in three and after both modalities in seven patients. Biopsy confirmed the
      presence of viable tumour in two patients. Two additional patients experienced
      progressive disease or relapse. The sensitivity and negative predictive value of
      FDG-PET/CT using the London criteria to indicate residual tumour detectable by
      biopsy were 100%, but specificity was low (60%), as was the positive predictive
      value (25%). Thus, in this study, a negative FDG-PET/CT finding was a good
      indicator of complete remission. However, because false-positive FDG-PET/CT
      findings are common, biopsy and close monitoring are required for accurate
      determination of residual disease in individual patients. 

PMID- 25382496
TI  - Benthic foraminifera for environmental monitoring: a case study in the central
      Adriatic continental shelf.
AB  - A study of benthic foraminifera was carried out in sediment samples collected
      from the central Adriatic coast of Italy, near the Ancona harbour and the
      Falconara Marittima oil refinery, in order to validate and support their use as
      bioindicators of ecosystem quality. On the basis of a principal component
      analysis (PCA), three biotopes (following the bathymetric gradient) have been
      documented, showing that the distribution pattern of benthic foraminifera is
      principally related to riverine inputs, organic matter contents at the seafloor,
      and sediment grain size. We observed higher abundances of opportunistic, low
      oxygen tolerant taxa along the coastline, thus being representative of polluted
      environmental conditions. Near the Falconara Marittima oil refinery, the
      microfaunal assemblages is characterized by the absence of living specimens and
      by a low diversity associated with the dominance of opportunistic species. At
      this site, aberrant tests were also found. The data point out that Ammonia
      parkinsoniana and Quinqueloculina seem to be the most sensitive taxa and can be
      considered as good bioindicators of environmental stress in this area. This study
      confirms that faunal composition and morphology of benthic foraminifera respond
      to human-induced environmental perturbations, making their study potentially
      useful for biomonitoring in coastal-marine areas. 

PMID- 25382497
TI  - Surfactants in atmospheric aerosols and rainwater around lake ecosystem.
AB  - This study was conducted to determine the composition of surfactants in
      atmospheric aerosols and rainwater in the vicinity of Lake Chini, Malaysia.
      Samples of atmospheric aerosol and rainwater were collected between March and
      September 2011 using a high volume air sampler (HVAS) and glass bottles equipped
      with funnel. Colorimetric analysis was undertaken to determine the concentration
      of anionic surfactants as methylene blue active substances (MBAS) and cationic
      surfactants as disulphine blue active substances (DBAS). The water-soluble ionic
      compositions were determined using inductively coupled plasma mass spectrometry
      for cations (Na, K, Mg and Ca) and ion chromatography equipped with a
      conductivity detector for anions (F(-), Cl(-), NO3(-), and SO4(2-)) and the
      Nessler Method was used to obtain the NH4(+) concentrations. The source
      apportionment of MBAS and DBAS in atmospheric aerosols was identified using a
      combination of principal component analysis (PCA) and multiple linear regression
      (MLR). The results revealed that the concentrations of surfactants in atmospheric
      aerosols and rainwater were dominated by anionic surfactants as MBAS. The
      concentration of surfactants as MBAS and DBAS was dominated in fine mode compared
      to coarse mode aerosols. Using PCA/MLR analysis, two major sources of atmospheric
      surfactants to Lake Chini were identified as soil dust (75 to 93%) and biomass
      burning (2 to 22%).

PMID- 25382498
TI  - Effects of linear alkylbenzene sulfonate on the growth and toxin production of
      Microcystis aeruginosa isolated from Lake Dianchi.
AB  - The exogenous organic pollutant linear alkylbenzene sulfonate (LAS) pollution and
      Microcystis bloom are two common phenomena in eutrophic lakes, but the effects of
      LAS alone on Microcystis remain unclear. In the present study, we investigated
      the effects of LAS on the growth, photochemical efficiency, and microcystin
      production of Microcystis aeruginosa in the laboratory. Results showed that low
      LAS (<=10 mg/L) concentrations improved the growth of M. aeruginosa (12 days of
      exposure). High LAS (20 mg/L) concentrations inhibited the growth of M.
      aeruginosa on the first 8 days of exposure; afterward, growth progressed. After
      12 days of exposure, the concentrations of chlorophyll a in algal cells were not
      significantly affected by any of LAS concentrations (0.05 to 20 mg/L) in the
      present study; by contrast, carotenoid and protein concentrations were
      significantly inhibited when LAS concentrations reached as high as 20 mg/L. After
      6 and 12 days of exposure, low LAS (<=10 mg/L) concentrations enhanced the
      maximal photochemical efficiency (Fv/Fm) and the maximal electron transport rate
      (ETRmax) of M. aeruginosa. Furthermore, LAS increased the microcystin production
      of M. aeruginosa. Extracellular and intracellular microcystin contents were
      significantly increased after M. aeruginosa was exposed to high LAS
      concentrations. Our results indicated that LAS in eutrophic lakes may increase
      the risk of Microcystis bloom and microcystin production. 

PMID- 25382499
TI  - Electron donors and co-contaminants affect microbial community composition and
      activity in perchlorate degradation.
AB  - Although microbial reduction of perchlorate (ClO4(-)) is a promising and
      effective method, our knowledge on the changes in microbial communities during
      ClO4(-) degradation is limited, especially when different electron donors are
      supplied and/or other contaminants are present. Here, we examined the effects of
      acetate and hydrogen as electron donors and nitrate and ammonium as co
      contaminants on ClO4(-) degradation by anaerobic microcosms using six treatments.
      The process of degradation was divided into the lag stage (SI) and the
      accelerated stage (SII). Quantitative PCR was used to quantify four genes: pcrA
      (encoding perchlorate reductase), cld (encoding chlorite dismutase), nirS
      (encoding copper and cytochrome cd1 nitrite reductase), and 16S rRNA. While the
      degradation of ClO4(-) with acetate, nitrate, and ammonia system (PNA) was the
      fastest with the highest abundance of the four genes, it was the slowest in the
      autotrophic system (HYP). The pcrA gene accumulated in SI and played a key role
      in initiating the accelerated degradation of ClO4(-) when its abundance reached a
      peak. Degradation in SII was primarily maintained by the cld gene. Acetate
      inhibited the growth of perchlorate-reducing bacteria (PRB), but its effect was
      weakened by nitrate (NO3(-)), which promoted the growth of PRB in SI, and
      therefore, accelerated the ClO4(-) degradation rate. In addition, ammonia
      (NH4(+)), as nitrogen sources, accelerated the growth of PRB. The bacterial
      communities' structure and diversity were significantly affected by electron
      donors and co-contaminants. Under heterotrophic conditions, both ammonia and
      nitrate promoted Azospira as the most dominant genera, a fact that might
      significantly influence the rate of ClO4(-) natural attenuation by degradation.

PMID- 25382500
TI  - Evidence for existence of quorum sensing in a bioaugmented system by acylated
      homoserine lactone-dependent quorum quenching.
AB  - The introduction of a gene, strain, or microbial consortium into an indigenous
      bacterial population is known as bioaugmentation. This technique has been
      proposed as an effective strategy for accelerating and enhancing the removal of
      recalcitrant and toxic compounds during wastewater treatment. In this study,
      three types of reactors were used to test whether quorum sensing plays an
      important role in bioaugmented systems. Reverse transcriptase polymerase chain
      reaction showed that the inoculated strain, HF-1, successfully colonized in the
      bioaugmented reactor. Meanwhile, no HF-1 colonization was observed in the quorum
      quenching and non-bioaugmented reactors. Removal of nicotine in the bioaugmented
      reactor was almost 100%, and removal of total organic carbon (TOC) was higher
      than 50%. However, less than 20% of nicotine and 30% of TOC was removed in quorum
      quenching and non-bioaugmented reactors. Moreover, the release of acylated
      homoserine lactones reached the threshold for HF-1 biofilm formation in
      bioaugmented reactors but not in quorum-quenching or non-bioaugmented reactors.
      The addition of porcine kidney acylase I, a quenching reagent, to the quorum
      quenching reactor hampered the colonization of HF-1. Together, these results
      demonstrate that quorum sensing plays an important role in HF-1 colonization of
      bioaugmented systems.

PMID- 25382501
TI  - POCIS passive samplers as a monitoring tool for pharmaceutical residues and their
      transformation products in marine environment.
AB  - In the last years, several scientific studies have shown that carbamazepine (CBZ)
      is one of the most frequently detected pharmaceutical in aquatic environment.
      However, little data is available on its detection and its transformation
      products (TPs) in marine water. The use of polar organic chemical integrative
      sampling (POCIS) passive samplers as a semi-quantitative and qualitative tool for
      screening of pharmaceuticals and TPs in seawater has been studied. Furthermore,
      the uptake rates of the target compounds were also determined under laboratory
      experiments to characterize the levels accumulated in devices. The results
      confirmed the presence of residues of anticonvulsant CBZ as well as some of its
      main metabolites, over a 1-year monitoring campaign carried out in French coast
      on the Mediterranean Sea. The work reports for the first time the presence of two
      TPs (10,11-dihydro-10,11-trans-dihydroxycarbamazepine (TRANS) and 10-hydroxy
      10,11-dihydrocarbamazepine (10OH)) in marine water. The results contribute in
      assessing the environmental and human health risk of pharmaceuticals on coastal
      areas. 

PMID- 25382503
TI  - Dermatoscope--the dermatologist's stethoscope.

PMID- 25382502
TI  - An integrated view of gamma radiation effects on marine fauna: from molecules to
      ecosystems.
AB  - Accidental release of nuclides into the ocean is causing health risks to marine
      organisms and humans. All life forms are susceptible to gamma radiation with a
      high variation, depending on various physical factors such as dose, mode, and
      time of exposure and various biological factors such as species, vitality, age,
      and gender. Differences in sensitivity of gamma radiation are also associated
      with different efficiencies of mechanisms related to protection and repair
      systems. Gamma radiation may also affect various other integration levels: from
      gene, protein, cells and organs, population, and communities, disturbing the
      energy flow of food webs that will ultimately affect the structure and
      functioning of ecosystems. Depending on exposure levels, gamma radiation induces
      damages on growth and reproduction in various organisms such as zooplankton,
      benthos, and fish in aquatic ecosystems. In this paper, harmful effects of gamma
      irradiated aquatic organisms are described and the potential of marine copepods
      in assessing the risk of gamma radiation is discussed with respect to
      physiological adverse effects that even affect the ecosystem level. 

PMID- 25382504
TI  - The trials of treating warts.

PMID- 25382505
TI  - Photochemotherapy (PUVA) in psoriasis and vitiligo.
AB  - Phototherapy with photochemotherapy (PUVA) is a well-known and well-studied
      modality for the treatment of psoriasis, which involves systemic or topical
      administration of chemicals known as psoralens and administration of ultraviolet
      light in increasing dosages after requisite time gap. PUVA is also used in the
      treatment of widespread vitiligo with moderately good results, though it is being
      surpassed by ultraviolet B (UVB), which is equally or slightly more efficacious
      with fewer side effects. PUVA induces repigmentation by varying mechanisms such
      as stimulation of melanogenesis, immunomodulation and activation of growth
      factors, though the exact mechanism is still speculative. There are various
      studies evaluating the efficacy of PUVA in psoriasis as well as in vitiligo,
      either alone or in combination with other immunosuppressants like azathioprine
      and calcipotriene. 

PMID- 25382506
TI  - The utility of dermoscopy in the diagnosis of evolving lesions of vitiligo.
AB  - BACKGROUND: Early lesions of vitiligo can be confused with various other causes
      of hypopigmentation and depigmentation. Few workers have utilized dermoscopy for
      the diagnosis of evolving lesions of vitiligo. AIM: To analyze the dermoscopic
      findings of evolving lesions in diagnosed cases of vitiligo and to correlate them
      histopathologically. METHODS: Dermoscopy of evolving lesions in 30 diagnosed
      cases of vitiligo was performed using both polarized light and ultraviolet light.
      RESULT: On polarized light examination, the pigmentary network was found to be
      reduced in 12 (40%) of 30 patients, absent in 9 (30%), and reversed in 6 (20%)
      patients; 2 patients (6.7%) showed perifollicular hyperpigmentation and 1 (3.3%)
      had perilesional hyperpigmentation. A diffuse white glow was demonstrable in 27
      (90%) of 30 patients on ultraviolet light examination. Melanocytes were either
      reduced in number or absent in 12 (40%) of 30 patients on histopathology.
      CONCLUSION: Pigmentary network changes, and perifollicular and perilesional
      hyperpigmentation on polarized light examination, and a diffuse white glow on
      ultraviolet light examination were noted in evolving vitiligo lesions.
      Histopathological examination was comparatively less reliable. Dermoscopy appears
      to be better than routine histopathology in the diagnosis of evolving lesions of
      vitiligo and can obviate the need for a skin biopsy.

PMID- 25382507
TI  - Intralesional immunotherapy with killed Mycobacterium indicus pranii vaccine for
      the treatment of extensive cutaneous warts.
AB  - BACKGROUND: Multiple cutaneous warts in adults are often symptomatic,
      cosmetically disabling, and difficult to treat. Killed Mycobacterium indicus
      pranii (previously known as Mycobacterium w, popularly known as Mw) vaccine has
      earlier been investigated in genital warts with encouraging results. OBJECTIVE:
      To evaluate the efficacy and safety profile of intralesional injected killed Mw
      vaccine for the treatment of extensive extragenital cutaneous warts. METHODS: In
      this study, a retrospective analysis of medical records was performed in patients
      with cutaneous warts treated with intralesional Mw vaccine. Only patients with
      more than 5 extra-genital warts, involving at least two body sites and which had
      not shown any signs of spontaneous regression over 6 months were treated with the
      vaccine. RESULTS: Forty four patients were treated with intralesional Mw vaccine.
      The mean number of warts was 41.5+/-25.7 with a disease duration of 3.1+/-2.5
      years. Complete clearance was achieved in 24 (54.5%) patients with a mean of
      3.4+/-1.1 intralesional injections. Cosmetically acceptable response to therapy
      (>75% clearance) was achieved in 37 (84.1%) patients. Wart response at distant
      sites was seen in 38 (86.3%) patients. Thirty-six patients (81.8%) experienced
      mild therapy-related side effects. Eighteen patients with complete response were
      followed up for 5.27+/-1.7 months and none had recurrence of lesions.
      CONCLUSIONS: Killed Mw vaccine is safe and effective in the treatment of
      extensive cutaneous warts. Larger, preferably randomized controlled trials are
      needed to assess its efficacy vis a vis standard therapies for warts.

PMID- 25382508
TI  - Safety and effectiveness of autoinoculation therapy in cutaneous warts: a double-
      blind, randomized, placebo--controlled study.
AB  - BACKGROUND: In spite of the availability of multiple treatment options, viral
      warts are known for their persistence and recurrence, causing frustration to
      patients and treating physicians. AIMS: To study the effectiveness and safety of
      autoinoculation as a treatment modality in cutaneous warts. METHODS: A double
      blind, placebo-controlled study was carried out. In the treatment group, full
      thickness warty tissue was excised, minced and implanted in a small dermal
      pocket. In the control group, warty tissue was only excised and not implanted,
      though a dermal pocket was made. Patients were evaluated every four weeks with
      lesion counts. The procedure was repeated at 4 and 8 weeks. Response was assessed
      at each visit and at 12 weeks. RESULTS: Forty-eight patients with cutaneous warts
      (male: female=32:16) were randomized into autoinoculation and control groups. The
      number of warts at baseline was comparable in both groups (P=0.293). Reduction in
      the number of warts was significantly more in the autoinoculation group (8.50+/
      13.88) than in the control group (10.04+/-5.80) from 8 weeks onwards (P=0.010).
      Complete resolution occurred only in the autoinoculation group, in 62.5% of
      cases. Adverse effects were seen in 11 patients, including infection of the donor
      site (5 cases), keloid formation (3) and hypopigmentation (3). CONCLUSION:
      Autoinoculation may be an effective therapeutic modality for cutaneous warts and
      two sessions may be required for optimum results.

PMID- 25382509
TI  - The effectiveness of finasteride and dutasteride used for 3 years in women with
      androgenetic alopecia.
AB  - BACKGROUND: The effectiveness of finasteride and dutasteride in women with
      androgenetic alopecia has been the subject of debate. AIM: To evaluate the
      effectiveness of finasteride and dutasteride on hair loss in women with
      androgenetic alopecia over a period of 3 years. METHODS: From a database
      containing systematically retrieved data on 3500 women treated for androgenetic
      alopecia between 2002 and 2012 with finasteride 1.25 mg or dutasteride 0.15 mg, a
      random sample stratified for age and type of medication was taken to yield 30
      women in two age categories: below and above 50 years, and for both medications.
      Hair thickness of the three thinnest hairs was measured from standardized
      microscopic images at three sites of the scalp at the start of the treatment and
      after 3 years of continuous medication intake. The macroscopic images were
      evaluated independently by three European dermatologists/hair experts. The
      diagnostic task was to identify the image displaying superior density of the
      hair. RESULTS: Both age categories showed a statistically significant increase in
      hair thickness from baseline over the 3-year period for finasteride and
      dutasteride (signed rank test, P=0.02). Hair thickness increase was observed in
      49 (81.7%) women in the finasteride group and in 50 (83.3%) women in the
      dutasteride group. On average, the number of post-treatment images rated as
      displaying superior density was 124 (68.9%) in the finasteride group, and 118
      (65.6%) in the dutasteride group. Dutasteride performed statistically
      significantly better than finasteride in the age category below 50 years at the
      central and vertex sites of the scalp. CONCLUSIONS: Finasteride 1.25 mg and
      dutasteride 0.15 mg given daily for 3 years effectively increased hair thickness
      and arrested further deterioration in women with androgenetic alopecia.

PMID- 25382510
TI  - Peripheral T-cell lymphoma at the injection site of influenza vaccination.
AB  - Pseudolymphomas or B-cell lymphoma at the vaccination site have been reported by
      several authors. However, onset of cutaneous T-cell lymphoma with cytotoxic
      features is a rare complication of vaccination. We report a 27-year-old man who
      developed a nodule and ulcer that arose at the site of injection of influenza
      vaccine. The neoplastic cells reacted positively for CD56, CD3, CD2, perforin,
      and granzyme B, but negatively for CD4, CD8, CD10, CD19, CD30, CD34, CD79, and
      betaF1. Molecular studies showed T-cell receptor gamma (TCR-gamma) chain
      monoclonal rearrangement. A diagnosis of peripheral T-cell lymphoma, not
      otherwise specified (NOS) was established. The patient had high fever,
      progressive liver dysfunction and a rapid fatal evolution. 

PMID- 25382511
TI  - Co-existence of extramammary Paget's disease and Bowen's disease of vulva.
AB  - Extramammary Paget's disease and Bowen's disease are histologically similar and
      immunohistochemistry is often required to make the diagnosis. We present a case
      of vulval Paget's disease with Bowen's disease in an elderly female. Strong
      positivity for cytokeratin 7, anti CAM 5.2, carcinoembryonic antigen (CEA) and
      periodic acid-Schiff (PAS) stain in clitoral, left labial and interface regions
      of the vulvectomy specimen confirmed the diagnosis of Paget's disease (PD) while
      positive staining for p63 in the right labial and interface regions helped in
      establishing the diagnosis of concurrent Bowen's disease (BD). 

PMID- 25382512
TI  - Eccrine syringofibroadenomatosis of the reactive subtype occurring in chronic
      poorly-controlled psoriasis.
AB  - Eccrine syringofibroadenomatosis (ESFA) is a rare adnexal tumor with
      acrosyringeal differentiation. Clinically, it can be mistaken for granulomatous
      infections or malignancies such as squamous cell carcinoma. Despite the rarity of
      the condition, we recently encountered two cases of the reactive subtype, which
      occurred in patients with poorly controlled chronic psoriasis. Both patients
      presented with long-standing, thick verrucous lesions on the lower legs. The
      diagnosis was made after histological examination and exclusion of infectious and
      neoplastic disorders. As this is a reactive disorder, management is focused on
      treating the underlying condition. Unfortunately, psoriasis was difficult to
      manage in both our patients and they defaulted further treatment. It is important
      to recognize ESFA as it can be confused with infectious or malignant disorders. 

PMID- 25382513
TI  - Rhinophyma-like cutaneous leishmaniasis.

PMID- 25382514
TI  - Clinical spectrum and antimicrobial resistance pattern of skin and soft tissue
      infections caused by community acquired-methicillin resistant Staphylococcus
      aureus.

PMID- 25382515
TI  - Ipsilateral galactorrhea following zoster of the T4 dermatome.

PMID- 25382516
TI  - Beard involvement in a man with frontal fibrosing alopecia.

PMID- 25382517
TI  - Bullous pemphigoid clinically presenting as lichen amyloidosis.

PMID- 25382518
TI  - Recurrent blisters in a case of resolving Stevens-Johnson syndrome/toxic
      epidermal necrolysis.

PMID- 25382519
TI  - Multiple cutaneous mastocytomas.

PMID- 25382520
TI  - Dyschromatosis symmetrica hereditaria with neurological abnormalities.

PMID- 25382521
TI  - Localized purpuric lesions in a case of classical pityriasis rosea.

PMID- 25382522
TI  - Subcutaneous phaeohyphomycosis caused by Bipolaris hawaiiensis in an
      immunocompetent patient.

PMID- 25382523
TI  - Disseminated cutaneous glomuvenous malformation.

PMID- 25382524
TI  - Pigmented Bowen's disease with prominent amyloid deposition on the eyelid.

PMID- 25382525
TI  - Adult onset Langerhans cell histiocytosis: report of two patients.

PMID- 25382526
TI  - Primary cutaneous extranodal natural killer/T-cell lymphoma.

PMID- 25382527
TI  - NK/T-cell lymphoma nasal type with an unusual clinical course.

PMID- 25382528
TI  - Malignant melanoma with metastasis to the male breast.

PMID- 25382529
TI  - Hidradenocarcinoma of the chest.

PMID- 25382530
TI  - Nodular hidradenoma of the scalp: a cytomorphological evaluation on fine needle
      aspiration cytology.

PMID- 25382531
TI  - Reversal of pseudo-ainhum with acitretin in Camisa's syndrome.

PMID- 25382532
TI  - Cold agglutinin disease-associated digital gangrene treated with plasmapheresis.

PMID- 25382533
TI  - An asymptomatic nodule on the finger. Diagnosis: Giant cell tumor of tendon
      sheath.

PMID- 25382534
TI  - H syndrome--four new patients from India.

PMID- 25382535
TI  - Thyroid dysfunctions in morphoea: a preliminary report.

PMID- 25382536
TI  - Late-onset apocrine chromhidrosis.

PMID- 25382537
TI  - Concomitant Darier's disease and Sjphigren's syndrome.

PMID- 25382538
TI  - Lichen planus pigmentosus inversus.

PMID- 25382539
TI  - Cutaneous Paecilomyces lilacinus infections in immunocompromised and
      immunocompetent patients: Retraction.

PMID- 25382540
TI  - Are we testing appropriately for low testosterone?: Characterization of tested
      men and compliance with current guidelines.
AB  - INTRODUCTION: Direct-to-consumer ads for testosterone replacement therapies have
      significantly increased over the past several years. Subsequently, testing for
      low serum testosterone has correspondingly increased. AIMS: We sought to
      determine the testing behaviors of practitioners as well as the characteristics
      of men who are undergoing testing for low testosterone. METHODS: Men aged 18-85
      years were queried from the institutional electronic data warehouse from 2009 to
      2012. Men were considered "tested" if their serum total testosterone level had
      been measured for any purpose. Tested men (TM) were compared with those not
      tested (NT). MAIN OUTCOME MEASURES: The frequency and timing of testing for low
      testosterone as well as patient demographics and clinical characteristics were
      compared between TM and NT using multivariable logistic regression models.
      RESULTS: Of the 321,674 total men, 10,133 (3.2%) underwent testing with a serum
      total testosterone (mean age of 55.2 +/- 14.1 years). The frequency of testing
      increased from 2.5% to 3.6% during the study period (P < 0.001). Multivariable
      analysis demonstrated that TM were significantly (P < 0.001) more likely to be
      Caucasian and have increased body mass index. In addition, TM were significantly
      more likely to have comorbid conditions including decreased libido (adjusted odds
      ratio [aOR] 10.0, 95% confidence interval [CI] 8.5, 11.7), infertility (aOR 4.8,
      95% CI 3.6, 6.6), erectile dysfunction (aOR 3.6, 95% CI 3.4, 3.8), osteoporosis
      (aOR 3.3, 95% CI 2.8, 3.8), depression (aOR 1.7, 95% CI 1.6, 1.8), prostate
      cancer (aOR 1.7, 95% CI 1.5, 1.8), hypertension (aOR 1.3. 95% CI 1.2, 1.4),
      chronic obstructive pulmonary disease (aOR 1.2, 95% CI 1.0, 1.4), and benign
      prostatic hyperplasia (aOR 1.2, 95% CI 1.1, 1.2). Among TM, only 889 (9%) men
      underwent testing between 7 am and 12 pm. CONCLUSIONS: The rate of testosterone
      testing is increasing with most testing practices directed toward a subset of men
      with comorbidities that are associated with hypogonadism. Compliance of
      physicians obtaining early morning serum testosterone levels is low. Further
      education of practitioners is required to appropriately test patients for
      hypogonadism.

PMID- 25382541
TI  - Community gastroenterologists can learn diminutive colon polyp histology
      characterization with narrow band imaging by a computer-based teaching module.
AB  - BACKGROUND AND AIM: The aim of the present study was to evaluate the impact of a
      computer-based teaching module on the performance of community
      gastroenterologists for characterization of diminutive polyps (<=5 mm) using
      narrow band imaging video clips. METHODS: Eighty videos were distributed in pre-
      and post-test DVD along with a 20-min audiovisual teaching presentation detailing
      endoscopic features differentiating adenomas from hyperplastic polyps using
      narrow band imaging. Each participant first reviewed pretest video clips and
      entered their responses for polyp histology and their confidence in diagnosis:
      high: >=90% or low: <90%. Following this, they reviewed the teaching module and
      assessed the post-test videos. Performance characteristics were calculated for
      pre- and post-test videos by comparing predicted histology with actual histology.
      Fisher's exact test was used for analysis and the kappa statistic was calculated
      for interobserver agreement. RESULTS: Fifteen gastroenterologists in community
      practice completed the study. Sensitivity, specificity, accuracy and negative
      predictive value in characterization of polyp histology improved significantly
      post-test compared to pretest. In post-test, accuracy was 92% for high-confidence
      diagnoses and the proportion of these increased with training from 46% (pretest)
      to 64% (post-test); P < 0.001. Interobserver agreement for diagnosis improved
      from fair (kappa = 0.23) in pretest to moderate (kappa = 0.56) in post-test.
      CONCLUSIONS: A teaching module using video clips can be used to teach community
      gastroenterologists polyp histology characterization by narrow band imaging.
      Whether this translates into real-time high accuracy in polyp detection needs to
      be further evaluated.

PMID- 25382542
TI  - In situ synchrotron IR microspectroscopy of CO2 adsorption on single crystals of
      the functionalized MOF Sc2(BDC-NH2)3.
AB  - Synchrotron radiation (SR) IR microspectroscopy has enabled determination of the
      thermodynamics, kinetics, and molecular orientation of CO2 adsorbed in single
      microcrystals of a functionalized metal-organic framework (MOF) under conditions
      relevant to carbon capture from flue gases. Single crystals of the small-pore
      MOF, Sc2 (BDC-NH2 )3 , (BDC-NH2 =2-amino-1,4-benzenedicarboxylate), with well
      defined crystal form have been investigated during CO2 uptake at partial
      pressures of 0.025-0.2 bar at 298-373 K. The enthalpy and diffusivity of
      adsorption determined from individual single crystals are consistent with values
      obtained from measurements on bulk samples. The brilliant SR IR source permits
      rapid collection of polarized spectra. Strong variations in absorbance of the
      symmetric stretch of the NH2 groups of the MOF and the asymmetric stretch of the
      adsorbed CO2 at different orientations of the crystals relative to the polarized
      IR light show that CO2 molecules align along channels in the MOF. 

PMID- 25382543
TI  - Strontium fructose 1, 6-diphosphate alleviate cyclophosphamide-induced
      oligozoospermia by improving antioxidant and inhibiting testicular apoptosis via
      FAS/FASL pathway.
AB  - This study investigated the treatment effects of a new compound, strontium
      fructose 1, 6-diphosphate (FDP-Sr), in cyclophosphamide (CP)-induced
      oligozoospermia. FDP-Sr, with extra high-energy supply, could reverse male
      hypogonadism in the testis. Male Wistar rats were randomly divided into three
      groups: control group (vehicle treated), CP group and CP + FDP-Sr group. Both CP
      group and CP + FDP-Sr groups were orally administered CP (20 mg kg(-1) )
      consecutively for the first 7 days to establish CP-induced testicular toxic
      models. Subsequently, CP group was given orally distilled water per day, whereas
      CP + FDP-Sr group was received FDP-Sr (200 mg kg(-1) ) for 49 days. Compared to
      the CP group, the FDP-Sr group showed significantly increased levels of serum
      testosterone, testis relative weights and epididymal sperm counts in rats. In
      addition, rats treated by FDP-Sr showed the recuperative activities of testicular
      marker enzymes and normalised levels of antioxidants in tissue. Testicular
      protection of FDP-Sr was further demonstrated by enhancing expression of P450scc,
      reducing ability of FAS/FASL and generating cytoprotection in the
      histopathological study. FDP-Sr appeared to possess an ability to attenuate CP
      induced reproduction toxicity via the activation of antioxidants and
      steroidogenesis enzymes, and alleviate oligozoospermia via inhibition of
      testicular apoptosis by FAS/FASL pathway.

PMID- 25382545
TI  - Parametric MR dynamic imaging for breast lesions characterization and prediction
      of lymph nodes involvement.
AB  - The main purpose of this study was to evaluate Gd-DTPA kinetics for the
      differential diagnosis between malignant and benign breast lesions. As a
      secondary aim, Gd-DTPA kinetics in malignant lesions was tested for predicting
      axillary lymph nodes involvement. Eighty-eight patients who underwent MRI for
      suspected breast tumor were selected from our database. All patients underwent
      the same acquisition protocol consisting of pre-contrast and dynamic
      contrastenhanced MRI. For all of them clinical and histopathological data were
      available. MR studies were performed on the same 1.5T scanner with a standard
      dedicated breast coil. Pre- and post-contrast dynamic images were used to
      calculate R1, R2 relaxation rates and proton density maps. The maximum influx
      rate (MIR) as well as the corresponding time (TMIR) were derived using R1
      relaxation rate maps and relative changes as a function of time. Histopatological
      analysis led to the diagnosis of 46 breast carcinomas and 42 benign lesions. All
      breast carcinomas and 24 out of 42 benign lesions showed contrast-enhancement.
      The mean MIR was 0.75+/-0.14 (SD) sec-(2) in malignant tumors and 0.53+/-0.14
      (SD) sec-(2) in contrast-enhancing benign breast lesions (p<0.0001). The TMIR was
      1.40+/-0.43 min and 3.01+/-1.92 min (mean+/-SD) in enhancing malignant and benign
      lesions, respectively (p<0.0001). In malignant tumors, TMIR was not significantly
      different in node negative and node positive carcinomas whereas MIR was
      significantly lower in node negative carcinomas (0.67+/-0.11 versus 0.83+/-0.12
      respectively, p<0.0001). Our findings suggest that quantitative assessment of Gd
      DTPA kinetics may be an additional tool characterized for enhancing breast
      lesions and for predicting axillary lymph nodes involvement in malignant breast
      carcinoma. 

PMID- 25382544
TI  - Identification of AREG and PLK1 pathway modulation as a potential key of the
      response of intracranial 9L tumor to microbeam radiation therapy.
AB  - Synchrotron microbeam radiation therapy (MRT) relies on the spatial fractionation
      of a synchrotron beam into parallel micron-wide beams allowing deposition of
      hectogray doses. MRT controls the intracranial tumor growth in rodent models
      while sparing normal brain tissues. Our aim was to identify the early biological
      processes underlying the differential effect of MRT on tumor and normal brain
      tissues. The expression of 28,000 transcripts was tested by microarray 6 hr after
      unidirectional MRT (400 Gy, 50 um-wide microbeams, 200 um spacing). The specific
      response of tumor tissues to MRT consisted in the significant transcriptomic
      modulation of 431 probesets (316 genes). Among them, 30 were not detected in
      normal brain tissues, neither before nor after MRT. Areg, Trib3 and Nppb were
      down-regulated, whereas all others were up-regulated. Twenty-two had similar
      expression profiles during the 2 weeks observed after MRT, including Ccnb1,
      Cdc20, Pttg1 and Plk1 related to the mitotic role of the Polo-like kinase (Plk)
      pathway. The up-regulation of Areg expression may indicate the emergence of
      survival processes in tumor cells triggered by the irradiation; while the
      modulation of the "mitotic role of Plk1" pathway, which relates to cytokinetic
      features of the tumor observed histologically after MRT, may partially explain
      the control of tumor growth by MRT. The identification of these tumor-specific
      responses permit to consider new strategies that might potentiate the antitumoral
      effect of MRT. 

PMID- 25382547
TI  - Very preterm children are at increased risk of reduced processing speed at 5
      years of age, predicted by typical complications of prematurity and prenatal
      smoking.
AB  - AIM: Very little is known about risk predictors for the development of reduced
      processing speed, which can cause intellectual problems in later life. This study
      identified risk predictors at 5 years of age in a population-based cohort of very
      preterm infants. METHODS: Between January 2003 and August 2006, all preterm
      infants born before 32 weeks of gestation in Tyrol were prospectively enrolled (n
      = 223), and 161 underwent a detailed examination at 5 years of age, including a
      cognitive assessment using the Wechsler Preschool and Primary Scale of
      Intelligence, third edition. The processing speed quotient is calculated on the
      basis of two subtests that assess symbol search and coding. The association
      between prenatal and postnatal factors and reduced processing speed was analysed
      by means of logistic regression analysis. RESULTS: Of 161 children tested, 55
      (34.2%) showed reduced processing speed. In 55.6% (n = 30) of these children,
      reduced processing speed was related to full-scale intelligence quotient scores
      of <85. Smoking in pregnancy, steroids for chronic lung disease and intracerebral
      haemorrhage predicted reduced processing speed at 5 years of age. CONCLUSION:
      More than a third of the very preterm children we tested showed reduced
      processing speed at 5 years of age, and predictors were typical complications of
      prematurity and smoking in pregnancy.

PMID- 25382546
TI  - Functional characterization of a conserved pair of NKR-P1 receptors expressed by
      NK cells and T lymphocytes in liver and gut.
AB  - Natural killer cell receptor protein 1 (NKR-P1) molecules are C-type lectin-like
      receptors modulating cellular responses toward target cells expressing C-type
      lectin-like related (Clr) molecules. Although the function of the prototypic rat
      NKR-P1A receptor and its inhibitory counterpart NKR-P1B are known, little is
      known about NKR-P1F and NKR-P1G apart from their promiscuity for Clr ligands.
      Here we generated mAbs against both receptors for phenotypic and functional
      analyses in rat tissues. NKR-P1F induced redirected lysis and robust Ca(2+)
      signaling in NK cells, which were prevented by simultaneous engagement of NKR
      P1G. NKR-P1G also inhibited NK-cell lysis of Clr transfectants. NKR-P1F was
      expressed by most NK cells and NKR-P1A(+) T cells in all tissues analyzed, and by
      many NKR-P1A(-) intestinal T cells, while NKR-P1G was expressed by subsets of
      these cells with highest prevalence in gut and liver. In the intraepithelial
      compartment, the proportion of NKR-P1A(+) and NKR-P1F(+) cells was high at birth
      and thereafter declined, while NKR-P1B(+) and NKR-P1G(+) cells increased with
      age. Expression levels were also modulated by cytokines, with an increase of NKR
      P1B and NKR-P1G induced by inflammatory cytokines, and a reduction of NKR-P1A by
      TGF-beta. The physiological impact of NKR-P1 receptors might thus be dependent on
      age, tissue, and inflammatory status. 

PMID- 25382548
TI  - The Opinions of GP's Patients About Suicide, Assisted Suicide, Euthanasia, and
      Suicide Prevention: An Italian Survey.
AB  - A survey about opinions on end-of-life issues of a population represented by
      1,171 people in the waiting room of general practitioners' surgeries was
      conducted in a province of northern Italy. Most subjects did not consider suicide
      as a reasonable option even in cases of a serious and incurable disease.
      Moreover, subjects did not consider euthanasia as a possible option either;
      however, they did express an opposite attitude when considering euthanasia in a
      third-person perspective. People with a personal history of suicidal behavior
      appear to present as a different population, overall expressing more open
      attitudes. 

PMID- 25382549
TI  - Controlling the spatial arrangement of organic magnetic anions adsorbed on
      epitaxial graphene on Ru(0001).
AB  - Achieving control over the self-organization of functional molecules on graphene
      is critical for the development of graphene technology in organic electronic and
      spintronic. Here, by using a scanning tunneling microscope (STM), we show that
      the electron acceptor molecule 7,7',8,8'-tetracyano-p-quinodimethane (TCNQ) and
      its fluorinated derivative 2,3,5,6-tetrafluoro-7,7',8,8'-tetracyano-p
      quinodimethane (F4-TCNQ), co-deposited on the surface of epitaxial graphene on
      Ru(0001), transform spontaneously into their corresponding magnetic anions and
      self-organize in two remarkably different structures. TCNQ forms densely packed
      linear magnetic arrays, while F4-TCNQ molecules remain as isolated non
      interacting magnets. With the help of density functional theory (DFT)
      calculations, we trace back the origin of this behavior in the competition
      between the intermolecular repulsion experienced by the individual charged
      anions, which tends to separate the molecules, and the delocalization of the
      electrons transferred from the surface to the molecules, which promotes the
      formation of molecular oligomers. Our results demonstrate that it is possible to
      control the spatial arrangement of organic magnetic anions co-adsorbed on a
      surface by means of chemical substitution, paving the way for the design of two
      dimensional fully organic magnetic structures on graphene and on other surfaces. 

PMID- 25382550
TI  - Detecting peptidic drugs, drug candidates and analogs in sports doping: current
      status and future directions.
AB  - With the growing availability of mature systems and strategies in biotechnology
      and the continuously expanding knowledge of cellular processes and involved
      biomolecules, human sports drug testing has become a considerably complex field
      in the arena of analytical chemistry. Proving the exogenous origin of peptidic
      drugs and respective analogs at lowest concentration levels in biological
      specimens (commonly blood, serum and urine) of rather limited volume is required
      to pursue an action against cheating athletes. Therefore, approaches employing
      chromatographic-mass spectrometric, electrophoretic, immunological and combined
      test methods have been required and developed. These allow detecting the misuse
      of peptidic compounds of lower (such as growth hormone-releasing peptides, ARA
      290, TB-500, AOD-9604, CJC-1295, desmopressin, luteinizing hormone-releasing
      hormones, synacthen, etc.), intermediate (e.g., insulins, IGF-1 and analogs,
      'full-length' mechano growth factor, growth hormone, chorionic gonadotropin,
      erythropoietin, etc.) and higher (e.g., stamulumab) molecular mass with desired
      specificity and sensitivity. A gap between the technically possible detection and
      the day-to-day analytical practice, however, still needs to be closed. 

PMID- 25382551
TI  - Erratum.
AB  - [This corrects the article on p. 509 in vol. 8, PMID: 20019937.]. 

PMID- 25382552
TI  - Pyrene degradation accelerated by constructed consortium of bacterium and
      microalga: effects of degradation products on the microalgal growth.
AB  - Abundant microbes including bacteria, fungi, or algae are capable of biodegrading
      polycyclic hydrocarbons (PAHs). However, pure cultures never occur in the
      contaminated environments. This study aimed to understand the general potential
      mechanisms of interactions between microbes under pollution stress by
      constructing a consortium of PAH-degrading microalga (Selenastrum capricornutum)
      and bacterium (Mycobacterium sp. strain A1-PYR). Bacteria alone could grow on the
      pyrene, whereas the growth of algae alone was substantially inhibited by the
      pyrene of 10 mg L(-1). In the mixing culture of algae and bacteria, the growth
      rate of algae was significantly increased from day 4 onward. Rapid bacterial
      degradation of pyrene might mitigate the toxicity of pyrene to algae. Phenolic
      acids, the bacterial degradation products of pyrene, could serve as the
      phytohormone for promoting algal growth in the coculture of algae and bacteria.
      In turn, bacterial growth was also enhanced by the algae presented in the mixing
      culture. Consequently, the fastest degradation of pyrene among all biodegradation
      systems was achieved by the consortium of algae and bacteria probably due to such
      interactions between the two species by virtue of degradation products. This
      study reveals that the consortium containing multiple microbial species is high
      potential for microbial remediation of pyrene-contaminated environments, and
      provides a new strategy to degrade the recalcitrant PAHs. 

PMID- 25382553
TI  - The progress in adjuvant therapy after curative resection of liver metastasis
      from colorectal cancer.
AB  - Colorectal cancer liver metastases (CRLM) are common and found in almost 50% of
      patients with colorectal cancer. Surgical resection has proved to be the most
      effective therapy for metastatic colorectal cancer isolated to the liver and has
      yielded long term survival. However, recurrence frequently occurs within the
      remaining liver as well as at extra-hepatic sites. The role of adjuvant therapy
      has been investigated in many studies but has still been controversial until now.
      This review examines the incorporation of adjuvant systemic chemotherapy,
      regional chemotherapy with hepatic arterial infusion and molecular targeted
      therapy following liver resection for patients with CRLM, and summarized the
      advantage and adverse effects for these treatments. Finally, we propose the
      prospective of future adjuvant treatments to further improve prognosis. 

PMID- 25382554
TI  - Chemical constituents and bioactivities of Colla corii asini.
AB  - In China, Colla corii asini is a health-care food and traditional Chinese
      medicine widely used in life-nourishing and clinical hematic antanemic therapy
      for more than 2,000 years. In this paper we compiled the chemical constituents
      isolated and detected from Colla corii asini including amino acids,
      proteins/gelatins, polysaccharides, volatile substances, inorganic substances,
      etc. Meanwhile we investigated the biological activities of Colla corii asini,
      which have been reported over the past few decades, including, hematologic
      diseases inhibitory activities, anti-aging activity, antitumor activity,
      immunomodulatory activity, bone repair activity, anti-inflammatory activity,
      antifatigue activity, etc. However, few reports on the relationships between the
      chemical constituents and bioactivities have been found, further studies of Colla
      corii asini are still necessary to facilitate research and development in the
      future. 

PMID- 25382555
TI  - Isotryptoquivaline F, a new quinazolinone derivative with anti TNF-alpha activity
      from Aspergillus sp. CM9a.
AB  - Isotryptoquivaline F (1) was isolated from Aspergillus sp. CM9a, an endophytic
      fungus of Cephalotaxus mannii. The structure was elucidated by extensively 1D and
      2D NMR and HR ESI MS spectroscopy. It has good TNF-alpha antagonistic effect, and
      can be used for anti-inflammatory drugs or other bioactive leading drugs. 

PMID- 25382556
TI  - Human mediator subunit MED15 promotes transcriptional activation.
AB  - In eukaryotes, the Mediator complex is an essential transcriptional cofactor of
      RNA polymerase II (Pol II). In humans, it contains up to 30 subunits and consists
      of four modules: head, middle, tail, and CDK/Cyclin. One of the subunits, MED15,
      is located in the tail module, and was initially identified as Gal11 in budding
      yeast, where it plays an essential role in the transcriptional regulation of
      galactose metabolism with the potent transcriptional activator Gal4. For this
      reason, we investigated the function of the human MED15 subunit (hMED15) in
      transcriptional activation. First, we measured the effect of hMED15 knockdown on
      cell growth in HeLa cells. The growth rate was greatly reduced. By
      immunostaining, we observed the colocalization of hMED15 with the general
      transcription factors TFIIE and TFIIH in the nucleus. We measured the effects of
      siRNA-mediated knockdown of hMED15 on transcriptional activation using two
      different transcriptional activators, VP16 and SREBP1a. Treatment with siRNAs
      reduced transcriptional activation, and this reduction could be rescued by
      overexpression of HA/Flag-tagged, wild-type hMED15. To investigate hMED15
      localization, we treated human MCF-7 cells with the MDM2 inhibitor Nutlin-3, thus
      inducing p21 transcription. We found that hMED15 localized to both the p53
      binding site and the p21 promoter region, along with TFIIE and TFIIH. These
      results indicate that hMED15 promotes transcriptional activation. 

PMID- 25382557
TI  - R-eriodictyol and S-eriodictyol exhibited comparable effect against H2O2-induced
      oxidative stress in EA.hy926 cells.
AB  - Eriodictyol is a flavanone well-known for its antioxidative activity. Due to a
      chiral carbon atom in position C-2, eriodictyol always exist in racemic form. In
      order to study the a Chiral Amylose-C column as chiral stationary phase. Online
      coupling HPLC-circular dichroism (CD) method was used for the determination of
      elution order and the absolute configurations of the two eluates. The protective
      effects of racemic and enantiomeric eriodictyol against H2O2-induced cytotoxicity
      with EA.hy926 cells were tested. The results showed that the two enantiomers of
      eriodictyol and the corresponding racemate were equipotent, suggesting that the
      configuration of the C-2 chiral center does not influence the cytoprotective
      activity against H2O2-induced oxidative stress in EA.hy926 cells. 

PMID- 25382558
TI  - HDAC1/3 dual selective inhibitors - new therapeutic agents for the potential
      treatment of cancer.
AB  - Histone deacetylases (HDACs) have attracted a great deal of interest as
      anticancer drug targets, and many HDAC inhibitors (HDACIs) have displayed
      clinical efficacy in treating specific tumors. However, all of these agents have
      significant toxicity, including fatigue, nausea, vomiting, thrombocytopenia, and
      neutropenia. Thus, increased effort is being directed toward developing selective
      HDACIs that are tolerated better and cause fewer adverse reactions. This article
      focuses mainly on the N-hydroxycinnamamide-based HDAC 1/3 dual inhibitors, and
      this article outlines the anticancer potential of these inhibitors. Since
      selective HDAC1/3 inhibitors may cause fewer adverse reactions than selective pan
      HDACIs and selective Class Iota inhibitors in clinical settings, further study of
      their mechanism of anticancer activity and optimization of their structure is
      warranted. 

PMID- 25382559
TI  - Drug development for controlling Ebola epidemic - a race against time.
AB  - The Ebola outbreak in West Africa this year is causing global panic. The high
      mortality of this disease is largely due to lack of effective preventive vaccines
      or therapeutic drugs. Realizing the gravity and urgency in controlling the
      epidemic, governments and drug companies across the world have taken many strong
      measures to speed up the process of drug development. Several representative
      candidate drugs that demonstrate potent anti-Ebola activity in preclinical
      studies have been pushed forward to higher research stages to obtain an earlier
      official license. It is expected that proven preventive or therapeutic regimens
      could be established in the near future. 

PMID- 25382560
TI  - Microbial safety and quality of fresh herbs from Los Angeles, Orange County and
      Seattle farmers' markets.
AB  - BACKGROUND: Farmers' markets have been growing in popularity in the United
      States, but the microbial quality and safety of the food sold at these markets is
      currently unknown. The purpose of this study was to assess the microbial safety
      and quality of fresh basil, parsley and cilantro sold at farmers' markets in the
      Los Angeles, Orange County and greater Seattle areas. RESULTS: A total of 133
      samples (52 basil, 41 cilantro and 40 parsley) were collected from 13 different
      farmers' markets and tested for Salmonella and generic Escherichia coli. One
      sample (parsley) was confirmed positive for Salmonella and 24.1% of samples were
      positive for generic E. coli, with a range of 0.70-3.15 log CFU g(-1) . Among the
      herbs tested, basil showed the highest percentage of samples with generic E. coli
      (26.9%), followed by cilantro (24.4%) and then parsley (20.0%). For 12% of
      samples, the levels of generic E. coli exceeded guidelines established by the
      Public Health Laboratory Service for microbiological quality of ready-to-eat
      foods. CONCLUSION: Overall, this study indicates the presence of Salmonella and
      generic E. coli in fresh herbs sold at farmers' markets; however, additional
      studies are needed to determine the sources and extent of contamination.

PMID- 25382561
TI  - Fetal growth and maternal glomerular filtration rate: a systematic review.
AB  - OBJECTIVE: Glomerular filtration rate (GFR) may influence concentrations of
      biomarkers of exposure and their etiologic significance in observational studies
      of associations between environmental contaminants and fetal growth. It is
      unknown whether the size of a developing fetus affects maternal GFR such that a
      small fetus leads to reduced plasma volume expansion (PVE), reduced GFR and
      subsequent higher concentrations of biomarkers in maternal serum. Our objective
      was to answer the question: "Is there an association between fetal growth and
      maternal GFR in humans?" METHODS: We adapted and applied the Navigation Guide
      systematic review methodology to assess the evidence of an association between
      fetal growth and GFR, either directly or indirectly via reduction in PVE.
      RESULTS: We identified 35 relevant studies. We rated 31 human and two non-human
      observational studies as "low" quality and two experimental non-human studies as
      "very low" quality. We rated all three evidence streams as "inadequate". The
      association between fetal growth and GFR was "not classifiable" according to pre
      specified definitions. CONCLUSIONS: There is currently insufficient evidence to
      support the plausibility of a reverse causality hypothesis for associations
      between exposure to environmental chemicals during pregnancy and fetal growth.
      Further research would be needed to confirm or disprove this hypothesis.

PMID- 25382562
TI  - Post-traumatic growth in survivors of allogeneic hematopoietic stem cell
      transplantation.
AB  - OBJECTIVE: This study aimed to understand factors related to post-traumatic
      growth (PTG) in patients who received allogeneic hematopoietic stem cell
      transplantation (HSCT), building baseline data for developing intervention
      programs to enhance PTG in HSCT survivors. METHODS: A self-report survey was
      administered to 100 patients who received HSCT within the last 5 years. The Post
      traumatic Growth Inventory, Impact of Event Scale-Revised, Perceived Social
      Support Scale, and Healthcare Professional's Support Scale were used, as well as
      items on demographic and clinical characteristics. Standard deviations of
      frequency and percentage, Chi-squared test between genders, independent t-test,
      correlation analysis between independent variables and extent of PTG, and
      regression analysis were conducted. RESULTS: The PTG levels of HSCT survivors
      were statistically significantly higher when participants were women, carried out
      more religious activities, had higher educational levels, or utilized nurse
      counseling. The 'intrusive thinking' traumatic impact subcategory, as well as
      social support and support from healthcare professionals, were found to be highly
      related to PTG scores. Upon multiple regression analysis, factors with greatest
      influence on PTG in HSCT survivors were support from healthcare professionals,
      followed in order, by social support, utilization of nurse counseling, intrusive
      thinking, and frequency of religious activities. CONCLUSIONS: We suggest
      implementing programs for HSCT patients to enhance support from healthcare
      professionals and to increase post-traumatic growth through greater utilization
      of nurse counseling, self-help meetings, and writing.

PMID- 25382563
TI  - A needs assessment of national hypertension organizations for hypertension
      prevention and control programs.

PMID- 25382564
TI  - [Whoever stops to become better, has stopped being good].

PMID- 25382568
TI  - Norfloxacin-induced subacute cutaneous lupus with erythema multiforme-like
      lesions: the enigma of the Rowell syndrome.

PMID- 25382573
TI  - [Journal-Club].

PMID- 25382574
TI  - [The wound seal -- certification possible as "Wound Clinic Center" according to
      criteria of DDG, DGG and ICW].

PMID- 25382577
TI  - [Laudation: Dr. med. Klaus Holzegel's 80th birthday].

PMID- 25382578
TI  - [Austrian Society of Dermatology and Venereology (OGDV)].

PMID- 25382579
TI  - [Working Group on Dermatological Oncology].

PMID- 25382580
TI  - Laparoscopic ventral mesh rectopexy for obstructed defaecation syndrome: time for
      a critical appraisal.

PMID- 25382581
TI  - Does the thermal plasticity of metabolic enzymes underlie thermal compensation of
      locomotor performance in the eastern newt (Notophthalmus viridescens)?
AB  - Eastern newts (Notophthalmus viridescens) upregulate the metabolic capacity of
      skeletal muscle in winter to compensate for thermodynamic effects on metabolism.
      However, whether this compensation facilitates locomotor performance at low
      temperature is unknown. Therefore, our aim was to determine if thermal
      acclimation of metabolic enzymes in muscle benefits locomotion. Eastern newts
      from southern Ohio were acclimated to cold (5 degrees C, 10:14 L:D) or warm (25
      degrees C, 14:10 L:D) conditions for 12 weeks. Following acclimation, we measured
      the locomotor performance (burst speed and time until exhaustion) and the
      activities of metabolic enzymes in skeletal muscle at 5-30 degrees C. Creatine
      kinase (CK) activity in skeletal muscle was higher in cold compared to warm
      acclimated newts, and cold-acclimated newts had a higher burst speed at low
      temperature compared to warm-acclimated newts. At low temperature, time until
      exhaustion was higher in cold compared to warm-acclimated newts, but the
      activities of citrate synthase (CS) and cytochrome c oxidase (CCO) in muscle were
      lower in cold compared to warm-acclimated newts. Together, these results
      demonstrate that eastern newts compensate for the effects of low temperature on
      locomotor performance. Whereas thermal compensation of CK activity is correlated
      with burst locomotion at low temperature, aerobic enzymes in skeletal muscle (CS
      and CCO) are not linked to compensation of sustained locomotion.

PMID- 25382582
TI  - Tribute to a nursing inquiry giant.

PMID- 25382583
TI  - Targeting Threats to the Therapeutic Alliance: A Primer for Marriage and Family
      Therapy Training.
AB  - Although theory and research highlight the importance of the client-therapist
      relationship, marriage and family therapy (MFT) training has historically
      centered on specific models, consisting of proprietary language and techniques,
      instead of common factors like the therapeutic alliance. In this article, we
      begin by making an argument for explicitly focusing on the therapeutic alliance
      in MFT training programs. Next, we highlight common alliance threats experienced
      by both faculty members and student therapists. We then integrate research
      informed principles with clinical wisdom to outline specific recommendations and
      concrete skill-building exercises for MFT educators and supervisors to use with
      their students to address these threats and advance training on the therapeutic
      alliance. 

PMID- 25382584
TI  - A putative greigite-type magnetosome gene cluster from the candidate phylum
      Latescibacteria.
AB  - The intracellular biomineralization of magnetite and/or greigite magnetosomes in
      magnetotactic bacteria (MTB) is strictly controlled by a group of conserved
      genes, termed magnetosome genes, which are organized as clusters (or islands) in
      MTB genomes. So far, all reported MTB are affiliated within the Proteobacteria
      phylum, the Nitrospirae phylum and the candidate division OP3. Here, we report
      the discovery of a putative magnetosome gene cluster structure from the draft
      genome of an uncultivated bacterium belonging to the candidate phylum
      Latescibacteria (formerly candidate division WS3) recently recovered by Rinke and
      colleagues, which contains 10 genes with homology to magnetosome mam genes of
      magnetotactic Proteobacteria and Nitrospirae. Moreover, these genes are
      phylogenetically closely related to greigite-type magnetosome genes that were
      only found from the Deltaproteobacteria MTB before, suggesting that the greigite
      genes may originate earlier than previously imagined. These findings indicate
      that some members of Latescibacteria may be capable of forming greigite
      magnetosomes, and thus may play previously unrecognized roles in environmental
      iron and sulfur cycles. The conserved genomic structure of magnetosome gene
      cluster in Latescibacteria phylum supports the hypothesis of horizontal transfer
      of these genes among distantly related bacterial groups in nature.

PMID- 25382585
TI  - Transgenic hybrid aspen trees with increased gibberellin (GA) concentrations
      suggest that GA acts in parallel with FLOWERING LOCUS T2 to control shoot
      elongation.
AB  - Bioactive gibberellins (GAs) have been implicated in short day (SD)-induced
      growth cessation in Populus, because exogenous applications of bioactive GAs to
      hybrid aspens (Populus tremula * tremuloides) under SD conditions delay growth
      cessation. However, this effect diminishes with time, suggesting that plants may
      cease growth following exposure to SDs due to a reduction in sensitivity to GAs.
      In order to validate and further explore the role of GAs in growth cessation, we
      perturbed GA biosynthesis or signalling in hybrid aspen plants by overexpressing
      AtGA20ox1, AtGA2ox2 and PttGID1.3 (encoding GA biosynthesis enzymes and a GA
      receptor). We found trees with elevated concentrations of bioactive GA, due to
      overexpression of AtGA20ox1, continued to grow in SD conditions and were
      insensitive to the level of FLOWERING LOCUS T2 (FT2) expression. As transgenic
      plants overexpressing the PttGID1.3 GA receptor responded in a wild-type (WT)
      manner to SD conditions, this insensitivity did not result from limited receptor
      availability. As high concentrations of bioactive GA during SD conditions were
      sufficient to sustain shoot elongation growth in hybrid aspen trees, independent
      of FT2 expression levels, we conclude elongation growth in trees is regulated by
      both GA- and long day-responsive pathways, similar to the regulation of flowering
      in Arabidopsis thaliana. 

PMID- 25382588
TI  - Venous coupler use for free-flap breast reconstructions: specific analyses of TMG
      and DIEP flaps.
AB  - PURPOSE: The purpose of this report was to present the results of comparisons of
      anastomotic data and flap complications in the use of venous coupler in breast
      reconstruction with the transverse musculocutaneous gracilis (TMG) flap and the
      deep inferior epigastric perforator (DIEP) flap. METHODS: Over a three-year
      period, 95 patients suffering from breast cancer were treated with mastectomy and
      breast reconstruction using free flaps. We performed 121 mechanical venous
      anastomoses for 105 flap procedures (80 DIEP and 25 TMG). The coupler size,
      anastomotic duration, number of anastomoses and postoperative complications were
      assessed for the entire series. RESULTS: The coupling device was perfectly
      suitable for all end-to-end anastomoses between the vein(s) of the flap and the
      internal mammary vein(s). No venous thrombosis occurred. The mean anastomotic
      time did not significantly differ between the DIEP (330 seconds) and TMG flap
      procedures (352 seconds) (P = 0.069). Additionally, there were no differences in
      coupling time observed following a comparison of seven coupler sizes (P = 0.066).
      The mean coupler size used during the TMG flap procedure was smaller than that
      used with the DIEP (2.4 mm versus 2.8 mm) (P < 0.001). The mean size was also
      smaller when double venous anastomoses were required compared to single
      anastomosis (2.4 mm versus 2.9 mm) (P < 0.001). The double branching was more
      frequent with the TMG flap (28%) than with the DIEP flap (11%). CONCLUSIONS: The
      coupler size used was smaller for the TMG procedure and when double venous
      anastomosis was performed. Additionally, anastomotic time was not affected by the
      flap type or coupler size used or by anastomosis number.

PMID- 25382589
TI  - Clinical course and prognosis of non-secretory multiple myeloma.
AB  - OBJECTIVE: To determine the prognosis of patients with non-secretory myeloma.
      METHODS: We studied 124 patients diagnosed with multiple myeloma who had no
      monoclonal protein detected on serum and urine immunofixation at diagnosis and on
      all subsequent follow-up testing (non-secretory myeloma). The overall survival
      (OS) of patients with non-secretory myeloma was compared with 6953 patients with
      typical myeloma seen during the same time period in whom a monoclonal protein was
      detected at the time of diagnosis. RESULTS: One hundred and twenty-four patients
      met criteria for non-secretory multiple myeloma. The median follow-up was 102
      months (range, 1-204 months). The median progression-free survival with initial
      therapy was 28.6 months, and the median OS was 49.3 months. There was a
      significant improvement in OS since 2001; median survival 43.8 months (prior to
      2001) vs. 99.2 months (2001-2012), P < 0.001. OS was superior in patients with a
      normal baseline FLC ratio (n = 10) compared to patients with an abnormal ratio (n
      = 19), medians not reached in both groups. Prior to 2001, OS was similar in non
      secretory myeloma (n = 86) and secretory myeloma (n = 4011), median 3.6 vs. 3.5
      yr, respectively, P = 0.63. However, among patients diagnosed between 2001 and
      2012, OS was superior in non-secretory myeloma (n = 36) compared to secretory
      myeloma (n = 2942), median 8.3 vs. 5.4 yr, respectively, P = 0.03. CONCLUSIONS:
      Non-secretory myeloma is an uncommon subtype of multiple myeloma. In the last
      decade, there has been an improvement in the survival of non-secretory myeloma
      and appears superior to secretory myeloma.

PMID- 25382590
TI  - Synthesis of new porphyrin-fullerene dyads capable of forming charge-separated
      states on a microsecond lifetime scale.
AB  - A series of covalently linked axially symmetric porphyrin-fullerene dyads with a
      rigid pyrrolo[3,4-c]pyrrolic linker enabling a fixed and orthogonal arrangement
      of the chromophores has been synthesized and studied by means of transient
      absorption spectroscopy and cyclic voltammetry. The lifetime of the charge
      separated state has been found to depend on the substituents on the porphyrin
      core, reaching up to 4 MUs for a species with meso-(p-MeOC6H4) substituents. The
      ground and excited electronic states of model compounds have been calculated at
      the DFT and TD-DFT B3LYP(6-31G(d)) levels of theory and analyzed with regard to
      the effect of the substituent on the stabilization of the charge-separated state
      in the porphyrin-fullerene ensemble with a view to explaining the observed
      dependence.

PMID- 25382591
TI  - Associations between CAMCOG-R subscale performance and formal education
      attainment in South African older adults.
AB  - ABSTRACT Background: The Cambridge Cognitive Examination-Revised (CAMCOG-R) is a
      sensitive screening tool for the early diagnosis of dementia in older adults.
      Overall performance on the CAMCOG-R is influenced by educational attainment. Few
      studies have, however, examined the association between educational attainment
      and performance on the individual CAMCOG subscales. We aimed to address this
      question in a sample from a low-and middle-income country (LAMIC), where resource
      constraints may have compromised access to, and quality of, education for many
      older adults. Methods: Participants, all over 60 years of age, were 51
      cognitively healthy community-dwelling volunteers and 47 individuals diagnosed
      with mild-moderate stage Alzheimer's disease (AD). Most participants had some
      high school education. They were administered the CAMCOG-R under standardized
      conditions. Results: Within both the control and AD patient groups, there were
      significant associations between years of completed education and CAMCOG-R total
      score, MMSE score, and CAMCOG-R Language subscale score. In both groups, level of
      education was not associated with scores on these subscales: in controls, recent
      memory, R 2 = .21, p = .055, learning memory, R 2 = .16, p = .398,
      attention/calculation, R 2 = .19, p = .467, and perception, R 2 = .18, p = .984;
      in AD patients, recent memory, R 2 = .14, p = .340, learning memory, R 2 = .03, p
      = .680, perception, R 2 = .09, p = .723, and attention/calculation, R 2 = .19, p
      = .097. Conclusions: Some CAMCOG-R subscale scores were more strongly associated
      with educational attainment than others. Importantly, however, performance on the
      recent memory and learning memory subscales was not affected by education. These
      subscales are sensitive indicators of amnestic mild cognitive impairment (MCI)
      and early AD. These subscales may therefore remain valid for use as an AD
      screening tool in resource-poor healthcare settings.

PMID- 25382592
TI  - Metabolic markers of MG-63 osteosarcoma cell line response to doxorubicin and
      methotrexate treatment: comparison to cisplatin.
AB  - A high resolution magic angle spinning NMR metabolomics study of the effects of
      doxorubicin (DOX), methotrexate (MTX) and cisplatin (cDDP) on MG-63 cells is
      presented and unveils the cellular metabolic adaptations to these drugs, often
      used together in clinical protocols. Although cDDP-treated cells were confirmed
      to undergo extensive membrane degradation accompanied by increased neutral
      lipids, DOX- and MTX-treated cells showed no lipids increase and different
      phospholipid signatures, which suggests that (i) DOX induces significant membrane
      degradation, decreased membrane synthesis, and apparent inhibition of de novo
      lipid synthesis, and (ii) MTX induces decreased membrane synthesis, while no
      membrane disruption or de novo lipid synthesis seem to occur. Nucleotide
      signatures were in apparent agreement with the different drug action mechanisms,
      a link having been found between UDP-GlcNAc and the active pathways of membrane
      degradation and energy metabolism, for cDDP and DOX, with a relation to oxidative
      state and DNA degradation, for cDDP. Correlation studies unveiled drug-specific
      antioxidative signatures, which pinpointed m- and s-inositols, taurine,
      glutamate/glutamine, and possibly creatine as important in glutathione
      metabolism. These results illustrate the ability of NMR metabolomics to measure
      cellular responses to different drugs, a first step toward understanding drug
      synergism and the definition of new biomarkers of drug efficacy. 

PMID- 25382593
TI  - Manipulating Morality: Third-Party Intentions Alter Moral Judgments by Changing
      Causal Reasoning.
AB  - The present studies investigate how the intentions of third parties influence
      judgments of moral responsibility for other agents who commit immoral acts. Using
      cases in which an agent acts under some situational constraint brought about by a
      third party, we ask whether the agent is blamed less for the immoral act when the
      third party intended for that act to occur. Study 1 demonstrates that third-party
      intentions do influence judgments of blame. Study 2 finds that third-party
      intentions only influence moral judgments when the agent's actions precisely
      match the third party's intention. Study 3 shows that this effect arises from
      changes in participants' causal perception that the third party was controlling
      the agent. Studies 4 and 5, respectively, show that the effect cannot be
      explained by changes in the distribution of blame or perceived differences in
      situational constraint faced by the agent. 

PMID- 25382594
TI  - Safety of therapeutic options for treating asthma in pregnancy.
AB  - INTRODUCTION: Pregnancy may be complicated by new onset or preexisting asthma.
      Asthma is one of the most common potentially serious medical problems to
      complicate pregnancy, and it may adversely affect both maternal quality of life
      and perinatal outcomes. Optimal management of asthma during pregnancy is thus
      important for both mother and baby. AREAS COVERED: This article reviews the
      recognition and management of asthma during pregnancy, paying close attention to
      the general principles of asthma medication use during pregnancy. Further, the
      article reviews the safety of asthma medications commonly used during pregnancy.
      In this article, the most pertinent recent publications are reported. Electronic
      databases, such as PUBMED, were searched for terms pregnan* or perinat* or
      obstet* and asthma or wheeze and treatment. EXPERT OPINION: Because pregnant
      women are generally excluded from clinical trials, there is a lack of adequate
      safety information for most medications taken during pregnancy. One of the most
      important requirements for the future is the availability of further safety
      information for asthma medications used during pregnancy that can also account
      for asthma control.

PMID- 25382595
TI  - The role of the glassy dynamics and thermal mixing in the dynamic nuclear
      polarization and relaxation mechanisms of pyruvic acid.
AB  - The temperature dependence of (1)H and (13)C nuclear spin-lattice relaxation rate
      1/T1 has been studied in the 1.6-4.2 K temperature range in pure pyruvic acid and
      in pyruvic acid containing trityl radicals at a concentration of 15 mM. The
      temperature dependence of 1/T1 is found to follow a quadratic power law for both
      nuclei in the two samples. Remarkably the same temperature dependence is
      displayed also by the electron spin-lattice relaxation rate 1/T1e in the sample
      containing radicals. These results are explained by considering the effect of the
      structural dynamics on the relaxation rates in pyruvic acid. Dynamic nuclear
      polarization experiments show that below 4 K the (13)C build up rate scales with
      1/T1e, in analogy to (13)C 1/T1 and consistently with a thermal mixing scenario
      where all the electrons are collectively involved in the dynamic nuclear
      polarization process and the nuclear spin reservoir is in good thermal contact
      with the electron spin system. 

PMID- 25382597
TI  - Mean platelet volume: a novel predictive marker for mortality in intensive care
      unit (ICU) patients?

PMID- 25382596
TI  - Transition from hospital to daily life: a pilot study.
AB  - PURPOSE: To assess the effect of nurse-led systematic rehabilitation counseling
      performed before discharge to prevent concerns in the hospital-to-home gap in
      rehabilitation of lung cancer patients after surgery. DESIGN AND METHOD: A quasi
      experimental intervention study. One hundred twenty patients with operable non
      small cell lung cancer admitted for surgery participated. Outcome was assessed by
      a validated self-rating questionnaire. The intervention was performed at the
      Department of Thoracic Surgery, University Hospital of Copenhagen, Denmark.
      RESULTS: Following nurse-led rehabilitation counseling, results showed that
      significantly more patients were offered physical rehabilitation, were aware of
      where to seek help after discharge, and experienced support to get back to daily
      life. CONCLUSIONS: A systematic rehabilitation counseling obliges some of the
      concerns lung cancer patients might have in the transition from hospital to daily
      life. CLINICAL RELEVANCE: Despite promising results, there is still a need to
      improve support for patients with lung cancer requiring rehabilitation.

PMID- 25382598
TI  - An isotope-coded fluorogenic cross-linker for high-performance target
      identification based on photoaffinity labeling.
AB  - A photoaffinity labeling (PAL)-based method for the rapid identification of
      target proteins is presented in which a high-performance chemical tag, an isotope
      coded fluorescent tag (IsoFT), can be attached to the interacting site by
      irradiation. Labeled peptides can be easily distinguished among numerous
      proteolytic digests by sequential detection with highly sensitive fluorescence
      spectroscopy and mass spectrometry. Subsequent MS/MS analysis provides amino acid
      sequence information with a higher depth of coverage. The combination of PAL and
      heterogeneous target-selecting techniques significantly reduces the amount of
      time and protein required for identification. An additional photocleavable moiety
      successfully accelerated proteomic analysis using cell lysate. This method is a
      widely applicable approach for the rapid and accurate identification of
      interacting proteins. 

PMID- 25382599
TI  - Density functional theory investigation of the layered uranium oxides U3O8 and
      U2O5.
AB  - Oxidation of UO(2) in the nuclear fuel cycle leads to formation of the layered
      uranium oxides. Here we present DFT simulations of U(2)O(5) and U(3)O(8) using
      the PBE + U functional to examine their structural, electronic and mechanical
      properties. We build on previous simulation studies of Amm2 alpha-U(3)O(8),
      P2(1)/m beta-U(3)O(8) and P6[combining macron]2m gamma-U(3)O(8) by including C222
      alpha-U(3)O(8), Cmcm beta-U(3)O(8) and Pnma delta-U(2)O(5). All materials are
      predicted to be insulators with no preference for ferromagnetic or
      antiferromagnetic ordering. We predict delta-U(2)O(5) contains exclusively U(5+)
      ions in an even mixture of distorted octahedral and pentagonal bipyramidal
      coordination sites. In each U(3)O(8) polymorph modelled we predict U(5+) ions in
      pentagonal bipyramidal coordination and U(6+) in octahedral coordination, with no
      U(4+) present. The elastic constants of each phase have been calculated and the
      bulk modulus is found to be inversely proportional to the volume per uranium ion.
      Finally, a number of thermodynamic properties are estimated, showing general
      agreement with available experiments; for example alpha- and beta-U(3)O(8) are
      predicted to be stable at low temperatures but beta-U(3)O(8) and gamma-U(3)O(8)
      dominate at high temperature and high pressure respectively.

PMID- 25382600
TI  - Development and use of a quantum dot probe to track multiple yeast strains in
      mixed culture.
AB  - Saccharomyces cerevisiae strains vary in their ability to develop and enhance
      sensory attributes of alcoholic beverages and are often found growing in mixed
      strain fermentations; however, quantifying individual strains is challenging due
      to quantification inaccuracies, low marker longevity, and compromised kinetics.
      We developed a fluorescent probe, consisting of glutathione molecules conjugated
      to a quantum dot (QD). Two S. cerevisiae strains were incubated with different
      coloured probes (QD attached to glutathione molecules, QD-GSH), fermented at
      multiple ratios, and quantified using confocal microscopy. The QD method was
      compared with a culture method using microsatellite DNA analysis (MS method).
      Probes were taken up by an ADP1 encoded transporter, transferred from mother cell
      to daughter cell, detectable in strains throughout fermentation, and were non
      toxic. This resulted in a new quantification method that was more accurate and
      efficient than the MS method. 

PMID- 25382601
TI  - Bilateral first rib anomalous articulations with pseudarthroses mimicking healing
      fractures in an infant with abusive head injury.
AB  - Bilateral symmetric bone nodules were observed in the anterolateral first ribs of
      an infant with shaking injuries at autopsy. The location prompted diagnostic
      considerations of healing fractures versus anomalous articulations with
      pseudarthroses. The forensic pathologist worked with forensic anthropologists and
      pediatric radiologists to evaluate autopsy findings and compare premortem and
      postmortem X-rays. Gross examination of the bones by the pathologist and
      anthropologists confirmed bilateral, callus-like bone nodules in first-rib
      locations associated with pseudarthroses. Histologic examination of one of the
      bones further showed features most consistent with pseudarthrosis, not a healing
      fracture. Radiologists then compared multiple premortem and postmortem
      radiographs that showed no remodeling of the bone over a 2-week interval between
      the time of injury and death, which would be unexpected for a healing fracture in
      an infant. This multidisciplinary approach resulted in the appropriate diagnosis
      of pseudarthroses due to anomalous articulations, an uncommon finding in forensic
      pathology. 

PMID- 25382602
TI  - Letter to the editor-increased maternal body mass index and infant death-a
      forensic perspective.

PMID- 25382603
TI  - Inverse association between soya food consumption and insulin resistance in
      Japanese adults.
AB  - OBJECTIVE: The purpose of the present study was to examine the association
      between soya food consumption and insulin resistance using baseline data of the
      Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima,
      Japan. DESIGN: This cross-sectional study included 1274 subjects, aged 34-70
      years at baseline, living in Tokushima Prefecture between 2008 and 2013. Fasting
      blood samples were collected and information on lifestyle characteristics
      including soya food intake and medical history were obtained using a structured
      self-administered questionnaire. The homeostasis model assessment of insulin
      resistance (HOMA-IR) was measured and those with HOMA-IR >= 2.5 were defined as
      having insulin resistance. Multiple logistic regression models were used to
      analyse the association between soya product intake and the prevalence of insulin
      resistance. SETTING: Rural communities located in Tokushima Prefecture, Japan,
      between 2008 and 2013. SUBJECTS: A total of 1148 adults (565 men and 583 women),
      aged 34-70 years. RESULTS: The frequency of intake of miso soup, total non-fried
      soya products and total soya products showed significant inverse dose-response
      relationships with insulin resistance, after adjustments for potential
      confounders. When soya product intake was calculated as soya protein and
      isoflavone, the odds ratios of insulin resistance decreased significantly as the
      estimated intake of soya protein increased. Furthermore, significant inverse dose
      response relationships were observed for total non-fried soya products and total
      soya products, after adjustment for total vegetable or total fibre consumption.
      CONCLUSIONS: The present results indicate that the intake of soya products and
      non-fried soya products is associated with reduced insulin resistance in the
      Japanese population.

PMID- 25382604
TI  - To tell or not to tell? Psychopathic traits and response integrity in youth
      delinquency surveys.
AB  - BACKGROUND: Individuals with high psychopathy scores are capable of providing
      valid self-reports on their own personality traits, but there have been no
      empirical studies of the effect of psychopathic features on responding to
      sensitive survey questions about specific behaviours. AIMS: The aim of this study
      is to investigate any relationship between facets of psychopathy and
      participants' willingness to report antisocial acts in youth delinquency surveys,
      controlling for demographic variables known to be associated with response
      integrity. METHODS: In a nationally representative sample of 4,855 Finnish
      mainstream adolescents aged 15-16, honesty of responding was assessed through
      direct response integrity questions related to violence, property crime and drug
      use. Psychopathy was measured with the Antisocial Process Screening Device - Self
      Report (APSD-SR). RESULTS: Callous-unemotional traits and, to a lesser degree,
      narcissistic features were associated with a dishonest response style, although
      the effect size was modest. CONCLUSIONS: Although psychopathy does not seem to
      influence the capability and willingness to report personality traits accurately,
      it may be associated with endorsing dishonest responses to questions about
      specific behaviours that have possible repercussions. Our findings suggest that
      previously observed associations between adolescents' self-reported delinquent
      behaviour and psychopathic traits may be underestimations of the strength of the
      effects.

PMID- 25382605
TI  - Gene expression profiles in the bovine corpus luteum (CL) during the estrous
      cycle and pregnancy: possible roles of chemokines in regulating CL function
      during pregnancy.
AB  - To determine functional differences between the corpus luteum (CL) of the estrous
      cycle and pregnancy in cows, gene expression profiles were compared using a 15 K
      bovine oligo DNA microarray. In the pregnant CL at days 20-25, 40-45 and 150-160,
      the expressions of 138, 265 and 455 genes differed by a factor of > 2-fold (P <
      0.05) from their expressions in the cyclic CL (days 10-12 of the estrous cycle).
      Messenger RNA expressions of chemokines (eotaxin, lymphotactin and ENA-78) and
      their receptors (CCR3, XCR1 and CXCR2) were validated by quantitative real-time
      PCR. Transcripts of eotaxin were more abundant in the CL at days 40-45 and 150
      160 of pregnancy than in the cyclic CL (P < 0.01). In contrast, the mRNA
      expressions of lymphotactin, ENA-78 and XCR1 were lower in the CL of pregnancy (P
      < 0.05). Messenger RNAs of CCR3 and CXCR2 were similarly detected both in the
      cyclic and pregnant CL. Tissue protein levels of eotaxin were significantly
      higher in the CL at days 150-160 of pregnancy than in the CL at other stages,
      whereas the lymphotactin protein levels in the CL at days 20-25 of pregnancy were
      lower (P < 0.05). Immunohistochemical staining showed that CCR3 was expressed in
      the luteal cells and that XCR1 was expressed in both the luteal cells and
      endothelial cells. Collectively, the different gene expression profiles may
      contribute to functional differences between the cyclic and pregnant CL, and
      chemokines including eotaxin and lymphotactin may regulate CL function during
      pregnancy in cows.

PMID- 25382606
TI  - Antioxidant effect of lemon balm (Melissa officinalis) and mate tea (Ilex
      paraguensys) on quality, lipid peroxidation and DNA oxidation of cryopreserved
      boar epididymal spermatozoa.
AB  - In this study, we investigated the protective ability of the addition of two
      antioxidant herb extracts, mate tea and lemon balm, on boar epididymal frozen
      thawed spermatozoa quality. Testes from mature boars were collected at local
      slaughterhouse, and sperm samples from epididymis were recovered by flushing.
      Spermatozoa were cryopreserved in lactose-egg yolk buffer supplemented with
      various concentrations of lemon balm and mate tea (0, 2.5, 5 and 10 g l(-1) )
      using the straw-freezing procedure. Motion parameters, acrosome and plasma
      membrane integrity, lipoperoxidation levels and DNA oxidative damage (8-hydroxy
      2'-deoxyguanosine base lesion) were evaluated. There were no differences among
      experimental groups with regard to motility characteristics, viability, acrosome
      and plasma membrane integrity; however, the highest concentration of lemon balm
      produced significant (P < 0.05) improvement in curvilinear trajectory,
      straightness and amplitude of lateral head displacement after thawing. The
      supplementation of freezing extender with mate tea and lemon balm reduced sperm
      lipid membrane peroxidation, and only mate tea protected DNA against oxidative
      damage during cryopreservation at 120 min post-thawing (P < 0.05). Mate tea
      experimental extender at concentration of 10 g l(-1) showed the lowest percentage
      of sperm oxidised DNA and malondialdehyde generation; thus, mate tea is a
      potential candidate such as antioxidant compound on boar sperm cryopreservation
      medium.

PMID- 25382607
TI  - Ag-nanoparticle-decorated porous ZnO-nanosheets grafted on a carbon fiber cloth
      as effective SERS substrates.
AB  - We report on the large-scale synthesis of Ag-nanoparticle (Ag-NP) decorated ZnO
      mesoporous-nanosheets (NSs) grafted on a flexible carbon fiber cloth (CFC), as
      sensitive and reproducible surface enhanced Raman scattering (SERS) substrates
      with excellent flexibility. The composite SERS-substrates are achieved by a
      combination of atomic layer deposition of ZnO-seeds on each fiber of the CFC
      (denoted as ZnO-seeds@CFC), chemical bath deposition and subsequent pyrolysis for
      the creation of ZnO-mesoporous-NSs grafted on ZnO-seeds@CFC, and ion-sputtering
      of Ag-NPs on the ZnO-mesoporous-NSs. As abundant SERS "hot spots" are generated
      from the electromagnetic coupling of the densely distributed Ag-NPs, and the
      semiconducting ZnO-mesoporous-NSs also have chemical supporting enhancement and
      distinct molecule adsorbing abilities, the composite SERS-substrates demonstrate
      high SERS-sensitivity with good signal reproducibility. As a trial for potential
      applications, the composite SERS-substrates were used to identify pesticides and
      highly toxic polychlorinated biphenyls (PCBs), and low concentrations down to 10(
      7) M for methyl parathion and 5 * 10(-6) M for PCB-77 were reached, respectively,
      showing promising potential for the SERS-based rapid detection of toxic organic
      pollutants in the environment. 

PMID- 25382608
TI  - Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T
      cell lymphoma not otherwise specified.
AB  - Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and
      aggressive tumours whose molecular pathogenesis and diagnosis are still
      challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and
      compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The
      differentially expressed miRNA signature was compared with the gene expression
      profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an
      independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared
      with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large
      cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK-. Differentially expressed miRNAs
      were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK- and
      15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate
      PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a
      multistep analysis was performed, which identified all miRNAs inversely
      correlated to different potential target genes. One of the most discriminant
      miRNAs was selected and its expression was found to affect the global GEP of the
      tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS
      from AITL and ALCL/ALK-, respectively. The diagnostic accuracy of this tool was
      very high (83.54%) and its prognostic value validated. 

PMID- 25382609
TI  - Efficacy and safety of long-term treatment with lenalidomide and dexamethasone in
      patients with relapsed/refractory multiple myeloma.
AB  - Data from two randomized pivotal, phase 3 trials evaluating the combination of
      lenalidomide and dexamethasone in relapsed/refractory multiple myeloma (RRMM)
      were pooled to characterize the subset of patients who achieved long-term benefit
      of therapy (progression-free survival ? 3 years). Patients with long-term benefit
      of therapy (n = 45) had a median duration of treatment of 48.1 months and a
      response rate of 100%. Humoral improvement (uninvolved immunoglobulin A) was more
      common in patients with long-term benefit of therapy (79% vs 55%; P = 0.002).
      Significant predictors of long-term benefit of therapy in multivariate analysis
      were age < 65 years (P = 0.03), beta2-microglobulin <2.5 mg/l (P = 0.002) and
      fewer prior therapies (P = 0.002). The exposure-adjusted incidence rate (EAIR) of
      grade 3-4 neutropenia was lower in patients with long-term benefit of therapy
      (13.9 vs 38.2 per 100 patient-years). The EAIR for invasive second primary
      malignancy was the same in patients with long-term benefit of therapy and other
      patients (1.7 per 100 patient-years). These findings indicate that patients with
      RRMM can experience long-term benefit with lenalidomide and dexamethasone
      treatment with manageable side effects.

PMID- 25382610
TI  - Nimbolide targets BCL2 and induces apoptosis in preclinical models of
      Waldenstroms macroglobulinemia.
AB  - Neem leaf extract (NLE) has medicinal properties, which have been attributed to
      its limonoid content. We identified the NLE tetranorterpenoid, nimbolide, as
      being the key limonoid responsible for the cytotoxicity of NLE in various
      preclinical models of human B-lymphocyte cancer. Of the models tested,
      Waldenstroms macroglobulinemia (WM) cells were most sensitive to nimbolide,
      undergoing significant mitochondrial mediated apoptosis. Notably, nimbolide
      toxicity was also observed in drug-resistant (bortezomib or ibrutinib) WM cells.
      To identify putative targets of nimbolide, relevant in WM, we used
      chemoinformatics-based approaches comprised of virtual in silico screening,
      molecular modeling and target-ligand reverse docking. In silico analysis revealed
      the antiapoptotic protein BCL2 was the preferential binding partner of nimbolide.
      The significance of this finding was further tested in vitro in RS4;11 (BCL2
      dependent) tumor cells, in which nimbolide induced significantly more apoptosis
      compared with BCL2 mutated (Jurkat BCL2(Ser70-Ala)) cells. Lastly,
      intraperitoneal administration of nimbolide in WM tumor xenografted mice,
      significantly reduced tumor growth and IgM secretion in vivo, while modulating
      the expression of several proteins as seen on immunohistochemistry. Overall, our
      data demonstrate that nimbolide is highly active in WM cells, as well as other B
      cell cancers, and engages BCL2 to exert its cytotoxic activity.

PMID- 25382611
TI  - Hypermethylation of the tumor suppressor gene PRDM1/Blimp-1 supports a
      pathogenetic role in EBV-positive Burkitt lymphoma.
AB  - PRDM1/Blimp-1 is a tumor suppressor gene in the activated B-cell subtype of
      diffuse large B-cell lymphomas. Its inactivation contributes to pathogenesis in
      this setting by impairing terminal B-cell differentiation induced by constitutive
      nuclear factor-kappaB activation. The role of PRDM1 in Burkitt lymphoma (BL)
      lymphomagenesis is not known. Here we identified hypermethylation of the promoter
      region and exon 1 of PRDM1 in all six Epstein-Barr virus (EBV)-positive BL cell
      lines and 12 of 23 (52%) primary EBV-positive BL or BL-related cases examined,
      but in none of the EBV-negative BL cell lines or primary tumors that we assessed,
      implying a tumor suppressor role for PRDM1 specifically in EBV-associated BL. A
      direct induction of PRDM1 hypermethylation by EBV is unlikely, as PRDM1
      hypermethylation was not observed in EBV-immortalized B lymphoblastoid cell
      lines. Treatment of EBV-positive BL cells with 5' azacytidine resulted in PRDM1
      induction associated with PRDM1 demethylation, consistent with transcriptional
      silencing of PRDM1 as a result of DNA methylation. Overexpression of PRDM1 in EBV
      positive BL cell lines resulted in cell cycle arrest. Our results expand the
      spectrum of lymphoid malignancies in which PRDM1 may have a tumor suppressor role
      and identify an epigenetic event that likely contributes to the pathogenesis of
      BL. 

PMID- 25382612
TI  - KIAA1549:BRAF fusion gene in pediatric brain tumors of various histogenesis.
AB  - The KIAA1549:BRAF fusion gene is considered a driver genetic event in pilocytic
      astrocytoma. We investigated a series of 69 pediatric brain neoplasms of diverse
      histogenesis and grade using the RT-PCR and sequencing. We detected the
      KIAA1549:BRAF fusion gene in five of 34 non-PA tumors (14.7%), that is, one
      glioblastoma, one anaplastic astrocytoma, one anaplastic pleomorphic
      xanthoastrocytoma, 1 ependymoma, and 1 Atypical Teratoid Rhabdoid Tumor. Our
      study showed that the K-B, although uncommon, it can be detected in non-PA tumors
      of various histogenesis and grading.

PMID- 25382613
TI  - RNA-based viral vectors.
AB  - The advent of reverse genetic approaches to manipulate the genomes of both
      positive (+) and negative (-) sense RNA viruses allowed researchers to harness
      these genomes for basic research. Manipulation of positive sense RNA virus
      genomes occurred first largely because infectious RNA could be transcribed
      directly from cDNA versions of the RNA genomes. Manipulation of negative strand
      RNA virus genomes rapidly followed as more sophisticated approaches to provide
      RNA-dependent RNA polymerase complexes coupled with negative-strand RNA templates
      were developed. These advances have driven an explosion of RNA virus vaccine
      vector development. That is, development of approaches to exploit the basic
      replication and expression strategies of RNA viruses to produce vaccine antigens
      that have been engineered into their genomes. This study has led to significant
      preclinical testing of many RNA virus vectors against a wide range of pathogens
      as well as cancer targets. Multiple RNA virus vectors have advanced through
      preclinical testing to human clinical evaluation. This review will focus on RNA
      virus vectors designed to express heterologous genes that are packaged into viral
      particles and have progressed to clinical testing. 

PMID- 25382615
TI  - Extracts of Celastrus orbiculatus exhibit anti-proliferative and anti-invasive
      effects on human gastric adenocarcinoma cells.
AB  - OBJECTIVE: To assess the effect of Celastrus orbiculatus (COE) on growth,
      invasion and migration of human gastric cancer MGC-803 cells and to explore the
      possible mechanism. METHODS: The effect of COE on cell viability, apoptosis,
      adhesion, invasion and migration were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) assay, flow cytometric, cell adhesion and
      transwell assay, respectively. The activity and expression of matrix
      metalloproteinase-9 (MMP-9) were determined by gelatin zymography, Western blot
      and quantitative real-time polymerase chain reaction analysis. Meanwhile, effects
      of COE on the expression of mitogen-activated protein kinases (MAPKs), serine
      threonine kinase (Akt), nuclear factor kappaB (NF-kappaB) were investigated with
      Western blot analysis. RESULTS: COE inhibited proliferation and induced apoptosis
      of MGC-803 cells in a dose-dependent manner. When treated with low-toxic (below
      80 MUg/mL) doses of COE, cell adhesion, invasion and migration were markedly
      suppressed. Furthermore, the gelatinolytic activity and expression of MMP-9 were
      also remarkably suppressed in a dose-dependent manner. In addition, upstream
      signaling pathways, including the phosphatidylinositol-3 kinase (PI3K)/Akt and NF
      kappaB, were suppressed by COE. Additionally, the PI3K/Akt inhibitor, LY294002,
      in treating MGC-803 cells potently suppressed cell invasion and migration as well
      as expression of MMP-9. Similarly, the combined treatment with COE and LY294002
      showed a synergistic effect compared with the treatment with COE or LY294002
      alone in MGC-803 cells. CONCLUSIONS: COE inhibits invasion and migration of MGC
      803 cells by reducing MMP-9 expression. It also inhibit PI3K/Akt and NF-kappaB
      signaling pathways, which may offer a novel approach for the treatment of human
      gastric cancer.

PMID- 25382614
TI  - Identification of eight novel mutations and transcript analysis of two splicing
      mutations in Chinese newborns with MCC deficiency.
AB  - 3-Methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive
      inborn error of leucine metabolism, caused by mutations in either MCCC1 or MCCC2
      gene. We identified eight novel mutations of MCCC1 or MCCC2 in six Chinese
      newborns screened by tandem mass spectrometry. Transcript analysis revealed that
      the novel splice mutation c.639+5G>T produced a normal transcript and a
      transcript of exon 6 skipping which led to truncated MCCC1 protein. The remaining
      seven novel mutations may cause structure damage and dysfunction of MCC as
      predicted by in silico analysis. In conclusion, our study expands the spectrum of
      mutations found in MCCC1 and MCCC2 and provides a rough prevalence of 1 of 68,333
      in Chinese population. Although the affected patients remained asymptomatic
      during follow-up, we hold the view that early detection through newborn
      screening, early intervention and follow-up may provide an important guidance to
      prevent subsequent metabolic disorders and deal with crisis later in life. 

PMID- 25382616
TI  - Diffuse large B-cell lymphoma: sites of extranodal involvement are a stronger
      prognostic indicator than number of extranodal sites in the rituximab era.
AB  - The National Comprehensive Cancer Network (NCCN) International Prognostic Index
      (IPI) is an enhanced prognostic tool that has identified some specific extranodal
      sites as a poor prognostic factor. We retrospectively analyzed 148 Taiwanese
      patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab,
      cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)-like regimens
      from January 2001 to December 2010 at the Tri-Service General Hospital. In
      univarate analysis, >= 2 extranodal involved sites had no significant prognostic
      relevance (p = 0.108), although extranodal involvement of the lung/pleura, liver,
      lower urinary tract or bone marrow was a statistically significant poor
      prognostic factor (p < 0.001). In multivariate analysis, specific extranodal
      sites had a stronger predictive value for poor prognosis (relative risk 3.654,
      95% confidence interval 1.514-8.815, p = 0.004) compared with the number of
      extranodal sites involved. This finding suggests that specific extranodal
      involved sites have prognostic value in the R era. 

PMID- 25382617
TI  - Neutrophil to lymphocyte ratio improves prognostic prediction of International
      Prognostic Index for patients with diffuse large B-cell lymphoma treated with
      rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone.
AB  - The purpose of this study was to analyze the pre- and post-treatment neutrophil
      to lymphocyte ratio (pre- and post-NLR) in combination with immunologic profiles
      in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab,
      cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). A total of
      447 newly diagnosed patients with DLBCL treated with R-CHOP were analyzed
      retrospectively. A pre-NLR >= 3 was independently associated with poor
      progression-free survival (PFS) (hazard ratio [HR] = 2.19, p < 0.001) and overall
      survival (OS) (HR = 2.89, p < 0.001). In patients with high pre-NLR, reduction of
      the post-NLR to < 3 after R-CHOP was correlated with improved survival. Low pre
      NLR (< 3) was also associated with a higher number of peripheral CD19 +
      lymphocytes (p = 0.049) and NK cells (p = 0.031). In conclusion, a pre-NLR >= 3
      was an independent prognostic factor for PFS and OS in patients with DLBCL
      treated with R-CHOP. 

PMID- 25382618
TI  - Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorder
      in children and young adults has similar molecular signature to extranodal nasal
      natural killer/T-cell lymphoma but shows distinctive stem cell-like phenotype.
AB  - We performed gene expression profiling in Epstein-Barr virus (EBV)-associated
      T/natural killer (NK)-cell lymphoproliferative disorder in children and young
      adults (TNKLPDC) in order to understand the molecular pathways deregulated in
      this disease and compared it with nasal-type NK/T-cell lymphoma (NKTL). The
      molecular and phenotypic signature of TNKLPDC is similar to NKTL, with
      overexpression of p53, survivin and EZH2. Down-regulation of EZH2 in TNKLPDC cell
      lines led to an increase in apoptosis and decrease in tumor viability, suggesting
      that EZH2 may be important for the survival of TNKLPDC cells and hence
      potentially a useful therapeutic target. Notably, our gene expression profiling
      revealed a distinctive enrichment of stem cell related genes in TNKLPDC compared
      to NKTL. This was validated by a significantly higher expression of aldehyde
      dehydrogenase 1 (ALDH1) in TNKLPDC cell lines compared to NKTL cell lines. The
      novel discovery of cancer stem cell properties in TNKLPDC has potential
      therapeutic implications in this group of disorders. 

PMID- 25382620
TI  - Linear free-energy relationships between a single gas-phase ab initio equilibrium
      bond length and experimental pKa values in aqueous solution.
AB  - Remarkably simple yet effective linear free energy relationships were discovered
      between a single ab initio computed bond length in the gas phase and experimental
      pKa values in aqueous solution. The formation of these relationships is driven by
      chemical features such as functional groups, meta/para substitution and
      tautomerism. The high structural content of the ab initio bond length makes a
      given data set essentially divide itself into high correlation subsets (HCSs).
      Surprisingly, all molecules in a given high correlation subset share the same
      conformation in the gas phase. Here we show that accurate pKa values can be
      predicted from such HCSs. This is achieved within an accuracy of 0.2 pKa units
      for 5 drug molecules. 

PMID- 25382621
TI  - Suboptimal B-cell antigen receptor signaling activity in vivo elicits germinal
      center counterselection mechanisms.
AB  - Syk and Zap-70 constitute a closely related nonreceptor protein tyrosine kinase
      family, of which both members are functionally indispensable for conferring their
      respective antigen receptors with enzymatic activity. In this study, we analyze
      the impact of altering BCR signaling output on B-cell germinal center (GC) fate
      selection by constitutive, as well as inducible, monoallelic Syk kinase loss in
      the presence of a Zap-70 knock-in rescue allele. Cre-mediated Syk deletion in
      Syk(flox/Zap-70) B cells lowers pErk, but not pAkt-mediated signaling.
      Surprisingly, the use of a B-cell-specific constitutive mb1-cre deleter mouse
      model showed that a small cohort of peripheral Syk(flox/Zap-70);mb1-cre B cells
      efficiently circumvents deletion, which ultimately favors these Syk-sufficient
      cells to contribute to the GC reaction. Using a developmentally unbiased
      Syk(flox/Zap-70);mb1-creER(T2) approach in combination with an inducible tdRFP
      allele, we further demonstrate that this monoallelic deletion escape is not fully
      explained by leakiness of Cre expression, but is possibly the result of
      differential Syk locus accessibility in maturing B cells. Altogether, this
      underscores the importance of proper Syk kinase function not only during central
      and peripheral selection processes, but also during GC formation and maintenance.

PMID- 25382622
TI  - Couples with diabetes and health-care providers: a grounded theory of
      preferential relating.
AB  - BACKGROUND: A collaborative health-care relationship is considered critical in
      managing chronic illness like diabetes. Poorly controlled diabetes can greatly
      diminish one's quality of life and lead to severe complications or even death.
      RATIONALE: Understanding how to improve the relationship between patients and
      their providers supports improved diabetes health outcomes. OBJECTIVE: We
      conducted a grounded theory study to examine the types of relationships that
      diabetic patients and their spouses prefer to form with their health-care
      providers. RESULTS: The analysis of in-depth interviews with 18 diabetic couples
      reveals four major relationship preferences that differ by the nature of
      caregiving and decision-making power demonstrated by the physician. CONCLUSION:
      Using illustrative examples, we show how the type of health-care relationship
      couples prefer is explained by their connection with one another and suggest
      implications for practitioners that expand current collaborative models of care.

PMID- 25382623
TI  - Progressive contraction of the latent HIV reservoir around a core of less
      differentiated CD4+ memory T Cells.
AB  - In patients who are receiving prolonged antiretroviral treatment (ART), HIV can
      persist within a small pool of long-lived resting memory CD4(+) T cells infected
      with integrated latent virus. This latent reservoir involves distinct memory
      subsets. Here we provide results that suggest a progressive reduction of the size
      of the blood latent reservoir around a core of less-differentiated memory subsets
      (central memory and stem cell-like memory (TSCM) CD4(+) T cells). This process
      appears to be driven by the differences in initial sizes and decay rates between
      latently infected memory subsets. Our results also suggest an extreme stability
      of the TSCM sub-reservoir, the size of which is directly related to cumulative
      plasma virus exposure before the onset of ART, stressing the importance of early
      initiation of effective ART. The presence of these intrinsic dynamics within the
      latent reservoir may have implications for the design of optimal HIV therapeutic
      purging strategies. 

PMID- 25382624
TI  - The association of statin use and gonado-sexual function in women: a
      retrospective cohort analysis.
AB  - INTRODUCTION: It has been hypothesized that statins reduce sex hormone
      biosynthesis through hepatic inhibition of cholesterol synthesis, which is a
      precursor of androstenedione and estradiol. Such a reduction has been associated
      with menstrual irregularities, menopausal disorders, infertility, and low libido,
      but studies are conflicting. Few studies have evaluated the clinical effects of
      statins on gonadal-sexual function in women. AIM: To compare the risk of gonado
      sexual dysfunction in statin users vs. nonusers. METHODS: This was a
      retrospective cohort study of all female, adult patients (30-85 years) enrolled
      in the Tricare Prime/Plus San Antonio catchment area. Using 79 baseline
      characteristics, we created a propensity score-matched cohort of statin users and
      nonusers. The study duration was divided into a baseline period (October 1, 2003
      to September 30, 2005) to describe patient baseline characteristics and a follow
      up period (October 1, 2005 to March 1, 2012) to determine patient outcomes.
      Statin users were defined as those prescribed a statin for >=3 months between
      October 1, 2004 and September 30, 2005. Logistic regression was used to determine
      the association of statin use with patient outcomes. MAIN OUTCOME MEASURES:
      Outcomes included menstrual disorders, menopausal disorders, infertility, and
      ovarian/sexual dysfunction during the follow-up period. Outcomes were identified
      using inpatient or outpatient International Classification of Diseases, Ninth
      Revision, Clinical Modification codes as defined by the Agency for Healthcare
      Research and Quality's Clinical Classifications Software. RESULTS: Of 22,706
      women who met study criteria, we propensity score-matched 2,890 statin users with
      2,890 nonusers; mean age 58 +/- 12 years. Statin use was not significantly
      associated with menstrual disorders (OR 0.97; 95% CI 0.81-1.16), menopausal
      disorders (OR 0.92; 95% CI 0.83-1.02), infertility (OR 0.79; 95% CI 0.36-1.73),
      or ovarian/sexual dysfunction (OR 1.18; 95% CI 0.83-1.70). CONCLUSIONS: Statin
      use was not associated with higher risk of gonado-sexual dysfunction in women.

PMID- 25382625
TI  - Morphological features of Herbst corpuscles in the oropharynx of the ostrich
      (Struthio camelus) and emu (Dromaius novaehollandiae).
AB  - The distribution of Herbst corpuscles in the oropharynx of the ostrich and emu
      has recently been documented. However, although the morphology of these
      mechanoreceptors is well known in neognathous birds, little structural
      information is available on the Herbst corpuscles of ratites. Tissue sections
      from those regions of the oropharynx known to possess a high concentration of
      Herbst corpuscles were sampled from ostrich and emu heads collected after
      slaughter and prepared for light and transmission electron microscopy. Intra-oral
      Herbst corpuscles in the ostrich and emu displayed the same basic components
      (capsule, outer zone, inner core and axon) described in neognathous birds.
      However, some important differences were observed, notably, the presence of
      myofibroblasts in the capsule, sensory cilia in cells of the outer layers, a
      relatively larger, less organized outer zone and narrower inner core, and
      variations in the shape of the axon. The previously unreported presence of
      myofibroblasts in the capsule possibly indicates its ability to contract, thus
      altering the tension of the capsule, which in turn has implications for the
      conduction of vibrational stimuli. The sensory cilia in the myofibroblasts of the
      capsule bordering the outer zone, and in the fibroblasts of the outer zone
      itself, may play a regulatory role in controlling the contraction of the capsule.
      Such a function has not previously been reported for Herbst corpuscles in any
      species of bird.

PMID- 25382626
TI  - The plasma membrane H(+) -ATPase AHA2 contributes to the root architecture in
      response to different nitrogen supply.
AB  - In this study the role of the plasma membrane (PM) H(+) -ATPase for growth and
      development of roots as response to nitrogen starvation is studied. It is known
      that root development differs dependent on the availability of different mineral
      nutrients. It includes processes such as initiation of lateral root primordia,
      root elongation and increase of the root biomass. However, the signal
      transduction mechanisms, which enable roots to sense changes in different mineral
      environments and match their growth and development patterns to actual conditions
      in the soil, are still unknown. Most recent comments have focused on one of the
      essential macroelements, namely nitrogen, and its role in the modification of the
      root architecture of Arabidopsis thaliana. As yet, not all elements of the signal
      transduction pathway leading to the perception of the nitrate stimulus, and hence
      to anatomical changes of the root, which allow for adaptation to variable ion
      concentrations in the soil, are known. Our data demonstrate that primary and
      lateral root length were shorter and lower in aha2 mutant lines compared with
      wild-type plants in response to a variable nitrogen source. This suggests that
      the PM proton pump AHA2 (Arabidopsis plasma membrane H(+) -ATPase isoform 2) is
      important for root growth and development during different nitrogen regimes. This
      is possible by controlling the pH homeostasis in the root during growth and
      development as shown by pH biosensors. 

PMID- 25382627
TI  - Transient hyperoxia does not affect regional cerebral tissue oxygen saturation in
      moderately preterm or term newborns.
AB  - AIM: Even short periods of hyperoxia may induce prolonged cerebral
      vasoconstriction in newborn infants, and this could theoretically lead to
      cerebral ischaemia even once normoxia is re-established. This study aimed to
      investigate the effect of brief hyperoxic exposures on regional cerebral tissue
      oxygen saturation (rStO2 ) and to evaluate whether any observed prolonged
      cerebral vasoconstriction was related to maturity. METHODS: The study included 30
      infants with a postmenstrual age of more than 32 weeks, who were treated with
      nasal continuous positive airway pressure and a fraction of inspired oxygen of
      <=0.3. The INVOS 5100C oximeter was used to measure rStO2 before, during and
      after two hyperoxic exposures. If hyperoxia induced a prolonged cerebral
      vasoconstriction, posthyperoxic rStO2 would be expected to decrease. RESULTS:
      rStO2 increased slightly after the first hyperoxic exposure, with a mean
      difference of 1.37% (95% CI 0.15, 2.6). After the second oxygen exposure, rStO2
      remained unchanged with a mean difference of -0.4% (95% CI -1.6, 0.78).
      Differences in rStO2 were not related to gestational age in either of the two
      hyperoxic episodes. CONCLUSION: We found no evidence to support the theory that
      transient hyperoxia induces prolonged cerebral vasoconstriction in infants with a
      postmenstrual age above 32 weeks.

PMID- 25382628
TI  - Evolving trends in nurse regulation: what are the policy impacts for nursing's
      social mandate?
AB  - We recognize a paradox of power and promise in the context of legislative and
      organizational changes in nurse regulation which poses constraints on nursing's
      capacity to bring voice and influence to pressing matters of healthcare and
      public policy. The profession is at an important crossroads wherein leaders must
      be well informed in political, economic and legislative trends to harness the
      profession's power while also navigating forces that may put at risk its central
      mission to serve society. We present a critical policy analysis of the impact of
      recent regulatory trends on what the International Council of Nurses considers
      nursing's three 'pillars' - the profession of nursing, socioeconomic welfare of
      nurses and nurse regulation. Themes surfacing from this analysis include
      regulatory discontinuity, a tightening of regulatory control, and an increasingly
      managerial governance culture. These themes illuminate insights and strategies
      required to renew and revitalize the social mandate of our profession amidst a
      climate of urgency in the questioning of nurse scholars with respect to the
      future of the profession. At this historic juncture, nurses must clearly
      understand the implications of legislative and organizational regulatory changes
      to ensure the profession contributes to full capacity in achieving health and
      health equity globally. 

PMID- 25382629
TI  - Comparison of dual-energy X-ray absorptiometry with six quantitative
      ultrasonometry devices in women with hip fractures.
AB  - OBJECTIVES: Dual-energy X-ray absorptiometry (DXA) is the gold standard for
      assessment of bone mineral density, an important risk factor for osteoporotic
      fractures. Recent reports suggest that quantitative ultrasonometry (QUS) is able
      to predict fractures; however, only limited data in women with hip fractures are
      available. METHODS: We examined 91 postmenopausal women who had sustained an
      osteoporosis-related hip fracture within the past 7 days using DXA and six
      different QUS devices and compared them with 91 healthy age-matched controls.
      RESULTS: Femoral neck (FN), total hip (TH) and lumbar spine (LS) T-scores were
      lower in women with hip fractures compared to matched controls: - 2.38 vs. - 1.64
      (p < 0.001), - 2.36 vs. - 1.44 (p < 0.001) and - 2.05 vs. - 1.50 (p = 0.41),
      respectively. The T-scores of the Achilles, Sahara, InSight and Omnisence QUS
      devices were also lower in patients with hip fractures compared to matched
      controls: - 3.20 vs. - 2.36 (p < 0.001), - 2.196 vs. - 1.761 (p = 0.005), - 2.631
      vs. - 1.849 (p < 0.001), - 3.707 vs. - 3.030 (p = 0.032), respectively. However,
      the T-scores of the DBM and QUS-2 did not differ between the two groups: - 4.543
      vs. - 4.324 (p = 0.352) and - 1.7 vs. - 2.0 (p = 0.465), respectively. Compared
      to DXA (hip), the odds ratios of the Achilles, InSight and Sahara were
      comparable, while the odds ratios of the DBM, Omnisence and QUS-2 were
      significantly lower (p <= 0.05). CONCLUSIONS: Compared to DXA, the Achilles,
      Sahara and InSight QUS devices showed similar hip fracture discrimination while
      the DBM, Omnisence and QUS-2 did not. Therefore, some QUS devices are able to
      identify a clinically meaningful risk factor in women at high risk of hip
      fracture.

PMID- 25382631
TI  - Mitigating the hydraulic compression of nanofiltration hollow fiber membranes
      through a single-step direct spinning technique.
AB  - Most nanofiltration (NF) membranes have been made through complicated multistep
      or thin-film composite processes. They also suffer the compaction issue that
      reduces permeate flux in pressure-driven filtration processes. A single-step
      coextrusion hollow fiber fabrication technique via immiscibility induced phase
      separation (I(2)PS) process is presented in this study to fabricate NF hollow
      fiber membranes. A protective layer is concurrently formed on top of the
      selective layer during the phase inversion process. The fabricated hollow fiber
      membrane has a narrow pore size distribution with a molecular weight cutoff
      (MWCO) of 470 Da. The outer layer of the I(2)PS hollow fiber is found to serve as
      a buffering layer that mitigates hydraulic compression on the compaction of dense
      selective layer and sublayer and helps to retain membrane performance during
      nanofiltration operations. The newly fabricated NF hollow fiber membrane exhibits
      an average pure water permeability of 3.2 L m(-2) h(-1) bar(-1) and shows good
      rejections toward the testing dyes. This study may offer a simple, direct, and
      cost-effective approach to fabricate NF hollow fiber membranes. 

PMID- 25382632
TI  - Examining platelet adhesion via Stokes flow simulations and microfluidic
      experiments.
AB  - While critically important, the platelet function at the high shear rates typical
      of the microcirculation is relatively poorly understood. Using a large scale
      Stokes flow simulation, Zhao et al. recently showed that RBC-induced velocity
      fluctuations cause platelets to marginate into the RBC free near-wall region
      [Zhao et al., Physics of Fluids, 2012, 24, 011902]. We extend their work by
      investigating the dynamics of platelets in shear after margination. An overall
      platelet adhesion model is proposed in terms of a continuous time Markov process
      and the transition rates are established with numerical simulations involving
      platelet-wall adhesion. Hydrodynamic drag and Brownian forces are calculated with
      the boundary element method, while the RBC collisions are incorporated through an
      autoregressive process. Hookean springs with first order bond kinetics are used
      to model receptor-ligand bonds formed between the platelet and the wall. The
      simulations are compared with in vitro microfluidic experiments involving
      platelet adhesion to Von Willebrand Factor (VWF) coated surfaces. 

PMID- 25382630
TI  - Type III transforming growth factor beta receptor regulates vascular and
      osteoblast development during palatogenesis.
AB  - BACKGROUND: Cleft palate occurs in up to 1:1,000 live births and is associated
      with mutations in multiple genes. Palatogenesis involves a complex choreography
      of palatal shelf elongation, elevation, and fusion. Transforming growth factor
      beta (TGFbeta) and bone morphogenetic protein 2 (BMP2) canonical signaling is
      required during each stage of palate development. The type III TGFbeta receptor
      (TGFbetaR3) binds all three TGFbeta ligands and BMP2, but its contribution to
      palatogenesis is unknown. RESULTS: The role of TGFbetaR3 during palate formation
      was found to be during palatal shelf elongation and elevation. Tgfbr3(-) (/) (-)
      embryos displayed reduced palatal shelf width and height, changes in
      proliferation and apoptosis, and reduced vascular and osteoblast differentiation.
      Abnormal vascular plexus organization as well as aberrant expression of arterial
      (Notch1, Alk1), venous (EphB4), and lymphatic (Lyve1) markers was also observed.
      Decreased osteoblast differentiation factors (Runx2, alk phos, osteocalcin,
      col1A1, and col1A2) demonstrated poor mesenchymal cell commitment to the
      osteoblast lineage within the maxilla and palatal shelves in Tgfbr3(-) (/) (-)
      embryos. Additionally, in vitro bone mineralization induced by osteogenic medium
      (OM+BMP2) was insufficient in Tgfbr3(-) (/) (-) palatal mesenchyme, but
      mineralization was rescued by overexpression of TGFbetaR3. CONCLUSIONS: These
      data reveal a critical, previously unrecognized role for TGFbetaR3 in vascular
      and osteoblast development during palatogenesis.

PMID- 25382633
TI  - Acute toxicity of 50 metals to Daphnia magna.
AB  - Metals are essential for human life and physiological functions but may sometimes
      cause disorders. Therefore, we conducted acute toxicity testing of 50 metals in
      Daphnia magna: EC50s of seven elements (Be, Cu, Ag, Cd, Os, Au and Hg) were < 100
      ug l(-1) ; EC50s of 13 elements (Al, Sc, Cr, Co, Ni, Zn, Se, Rb, Y, Rh, Pt, Tl
      and Pb) were between 100 and 1000 ug l(-1) ; EC50s of 14 elements (Li, V, Mn, Fe,
      Ge, As, In, Sn, Sb, Te, Cs, Ba, W and Ir) were between 1,001 and 100,000 ug l(-1)
      ; EC50s of six elements (Na, Mg, K, Ca, Sr and Mo) were > 100,000 ug l(-1) ; and.
      7 elements (Ti, Zr, Bi, Nb, Hf, Re and Ta) did not show EC50 at the upper limit
      of respective aqueous solubility, and EC50s were not obtained. Ga, Ru and Pd
      adhered to the body of D. magna and physically retarded the movement of D. magna.
      These metals formed hydroxides after adjusting the pH. Therefore, here, we
      distinguished this physical effect from the physiological toxic effect. The acute
      toxicity results of 40 elements obtained in this study were not correlated with
      electronegativity. Similarly, the acute toxicity results of metals including the
      rare metals were also not correlated with first ionization energy, atomic weight,
      atomic number, covalent radius, atomic radius or ionic radius.

PMID- 25382634
TI  - From false belief to friendship: commentary on Fink, Begeer, Peterson, Slaughter,
      and de Rosnay.
AB  - Fink, Begeer, Peterson, Slaughter, and de Rosnay (Brit. J. Dev. Psychol, 2015;
      33, 1-17) represent a welcome contribution in providing empirical evidence of the
      link from false belief understanding at Time 1 to mutual friendship 2 years
      later, controlling for several other possible contributors. This opens a new and
      important line of inquiry into the practical significance of a Theory of Mind. As
      is typical of pioneering research, further study is needed to address some
      issues; here, we point out some of these issues and then briefly discuss the
      broader implications of Fink et al.'s findings. 

PMID- 25382635
TI  - Insufficient vitamin D supplement use during pregnancy and early childhood: a
      risk factor for positional skull deformation.
AB  - Vitamin D insufficiency during pregnancy is associated with disturbed skeletal
      homeostasis during infancy. Our aim was to investigate the influence of adherence
      to recommendations for vitamin D supplement intake of 10 MUg per day (400 IU)
      during pregnancy (mother) and in the first months of life (child) on the
      occurrence of positional skull deformation of the child at the age of 2 to 4
      months. In an observational case-control study, two hundred seventy-five 2- to 4
      month-old cases with positional skull deformation were compared with 548 matched
      controls. A questionnaire was used to gather information on background
      characteristics and vitamin D intake (food, time spent outdoors and supplements).
      In a multiple variable logistic regression analysis, insufficient vitamin D
      supplement intake of women during the last trimester of pregnancy [adjusted odds
      ratio (aOR) 1.86, 95% (CI) 1.27-2.70] and of children during early infancy (aOR
      7.15, 95% CI 3.77-13.54) were independently associated with an increased risk of
      skull deformation during infancy. These associations were evident after
      adjustment for the associations with skull deformation that were present with
      younger maternal age and lower maternal education, shorter pregnancy duration,
      assisted vaginal delivery, male gender and milk formula consumption after birth.
      Our findings suggest that non-adherence to recommendations for vitamin D
      supplement use by pregnant women and infants are associated with a higher risk of
      positional skull deformation in infants at 2 to 4 months of age. Our study
      provides an early infant life example of the importance of adequate vitamin D
      intake during pregnancy and infancy.

PMID- 25382636
TI  - A deep-sequencing method detects drug-resistant mutations in the hepatitis B
      virus in Indonesians.
AB  - OBJECTIVE: The long-term administration of a nucleos(t)ide analogue (NA) for the
      treatment of chronic hepatitis B may encourage the emergence of viral mutations
      associated with drug resistance. Minor populations of viruses may exist before
      treatment, but are difficult to detect because of technological limitations.
      Identifying minor viral quasispecies should be useful in the clinical management
      of hepatitis B virus (HBV) infection. METHODS: Six treatment-naive Indonesian
      patients with chronic HBV infection participated in this study. The polymerase
      region of the HBV genome, including regions with known drug-resistant mutations,
      was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations
      were analyzed with Genomics Workbench software version 6.0.1 (CLC bio). RESULTS:
      The mean mapping reads for the six samples was 745,654, and the mean number of
      amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug
      resistant mutations in the reverse transcriptase region were identified in all
      patients, although the frequencies were low (0.12-1.06%). The proportions of the
      total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were
      >1.0%. CONCLUSION: Several known NA-resistant mutations were detected in
      treatment-naive patients in Indonesia using deep sequencing. Careful management
      of such patients is essential to prevent drug-resistant mutations from spreading
      to other patients.

PMID- 25382637
TI  - C/EBPbeta promotes angiogenesis through secretion of IL-6, which is inhibited by
      genistein, in EGFRvIII-positive glioblastoma.
AB  - To study the mechanisms underlying the IL-6-promoted angiogenic microenvironment
      in EGFRvIII-positive glioblastoma, VEGF expression in EGFRvIII-positive/negative
      tumors was determined by optical molecular imaging. Next, the HUVEC tube
      formation assay, Western blot, qPCR, RNA silencing, chromatin
      immunoprecipitation, luciferase reporter and ELISA assays were performed to
      examine the role of IL-6 and C/EBPbeta in the formation of the angiogenic
      microenvironment in EGFRvIII-positive tumors. Finally, in vitro and in vivo
      genistein treatment experiments were conducted to challenge the interaction
      between the IL-6 promoter and C/EBPbeta. Optical imaging revealed greater VEGF
      expression in EGFRvIII-positive tumor-bearing mice, suggesting an angiogenic
      microenvironment. In vitro experiments demonstrated that C/EBPbeta-mediated
      regulation of IL-6 was indispensable for maintenance of this angiogenic
      microenvironment. In contrast, genistein-mediated upregulation of CHOP impeded
      C/EBPbeta interaction with the IL-6 promoter, thus disturbing the angiogenic
      microenvironment. This more malignant microenvironment in EGFRvIII glioblastoma
      is generated, at least in part, by greater VEGF, IL-6 and C/EBPbeta expression.
      Interaction of C/EBPbeta with the IL-6 promoter maintains this angiogenic
      microenvironment, while disturbance of this dynamically balanced interaction
      inhibits EGFRvIII tumor proliferation by reducing both VEGF and IL-6 expression. 

PMID- 25382638
TI  - Effect of age on factor IX levels in symptomatic carriers of Haemophila B Leyden.

PMID- 25382639
TI  - Expression of monellin in a food-grade delivery system in Saccharomyces
      cerevisiae.
AB  - BACKGROUND: Genetically modified (GM) foods have caused much controversy.
      Construction of a food-grade delivery system is a desirable technique with
      presumptive impact on industrial applications from the perspective of bio-safety.
      The aim of this study was to construct a food-grade delivery system for
      Saccharomyces cerevisiae and to study the expression of monellin from the berries
      of the West African forest plant Dioscoreophyllum cumminsii in this system.
      RESULTS: A food-grade system for S. cerevisiae was constructed based on ribosomal
      DNA (rDNA)-mediated homologous recombination to enable high-copy-number
      integration of the expression cassette inserted into the rDNA locus. A copper
      resistance gene (CUP1) was used as the selection marker for yeast transformation.
      Because variants of transformants containing different copy numbers at the CUP1
      locus can be readily selected after growth in the presence of elevated copper
      levels, we suggest that this system would prove useful in the generation of
      tandemly iterated gene clusters. Using this food-grade system, a single-chain
      monellin gene was heterologously expressed. The yield of monellin reached a
      maximum of 675 mg L(-1) . CONCLUSION: This system harbors exclusively S.
      cerevisiae DNA with no antibiotic resistance genes, and it should therefore be
      appropriate for safe use in the food industry. Monellin was shown to be expressed
      in this food-grade delivery system. To our knowledge, this is the first report so
      far on expression of monellin in a food-grade expression system in S. cerevisiae.

PMID- 25382640
TI  - Association of hyperuricemia with conventional cardiovascular risk factors in
      elderly patients.
AB  - The relationship between serum uric acid (UA) and cardiovascular risk profile was
      investigated in 557 outpatients (415 women) aged 60 years and older. Patients
      were grouped according to a UA cutoff level of 5.5 mg/dL. Prevalence of obesity,
      hypertension, and impaired glucose metabolism was increased in women with higher
      UA, who had higher body mass index (37.7+/-6.9 vs 33.1+/-5.9 kg/m(2) , P<.001),
      waist circumference, and serum glucose and triglyceride concentrations than women
      with lower UA levels. Conversely, men with higher UA levels showed lower high
      density lipoprotein cholesterol and higher left ventricular mass than men with
      lower UA levels. Estimated glomerular filtration rate was reduced in patients
      with high UA levels of both sexes (65+/-17 vs 72+/-16 mL/min/1.73 m(2) , P<.001,
      for women; 70+/-16 vs 76+/-15 mL/min/1.73 m(2) , P<.03, for men). Grouping
      patients by sex-specific median UA concentrations produced similar results. These
      data indicate that, even in the elderly, UA clusters in a sex-specific fashion
      with features of metabolic syndrome and signs of target organ damage.

PMID- 25382641
TI  - The use of sling vs sphincter in post-prostatectomy urinary incontinence.
AB  - The artificial urinary sphincter (AUS) is considered the 'gold standard' in post
      prostatectomy urinary incontinence. However, in recent years, male slings have
      gained much popularity due to the ease of surgery, good functional results and
      low complications rates. This review systematically shows the evidence for the
      different sling systems, describes the working mechanism, and compares their
      efficacy against that of the AUS. Furthermore subgroups of patients are defined
      who are not suited to undergo sling surgery. 

PMID- 25382642
TI  - Modulation of Sinorhizobium meliloti quorum sensing by Hfq-mediated post
      transcriptional regulation of ExpR.
AB  - In Sinorhizobium meliloti, the timing of quorum sensing (QS)-dependent gene
      expression is controlled at multiple levels. RNA binding protein Hfq contributes
      to the regulation of QS signal production, and this regulation is exerted both in
      the manner that involves the acyl homoserine lactone receptor ExpR, and via expR
      independent mechanisms. In the expR+ strain of S. meliloti, deletion of hfq
      resulted in the hyper-accumulation of QS signals at low population densities,
      increased diversity of the QS signals in mid-to-late exponential phase and then
      led to a sharp decrease in QS signal accumulation in stationary phase.
      Quantitative polymerase chain reaction revealed that the accumulation of expR and
      sinI (but not sinR) mRNA was increased in the late exponential phase in an hfq
      dependent manner. A translational, but not transcriptional, expR-uidA reporter
      was controlled by hfq, while both transcriptional and translational sinI-uidA
      reporters were regulated in the hfq-dependent manner. In co-immunoprecipation
      experiments, expR mRNA was bound to and then released from Hfq, similar to the
      positive controls (small regulatory RNA SmrC9, SmrC15, SmrC16 and SmrC45).
      Neither sinI nor sinR transcripts were detected in the pool of RNA heat-released
      from Hfq-RNA complexes. Therefore, post-transcriptional regulator Hfq controls
      the production and perception of QS signals, and at higher population densities
      this control is mediated directly via interactions with expR. 

PMID- 25382650
TI  - The treatment of tissue defects related to the compartment syndrome occurring in
      the fibula osteocutaneous free flap donor area with vacuum assisted closure
      therapy.

PMID- 25382643
TI  - Direct capture and heterologous expression of Salinispora natural product genes
      for the biosynthesis of enterocin.
AB  - Heterologous expression of secondary metabolic pathways is a promising approach
      for the discovery and characterization of bioactive natural products. Herein we
      report the first heterologous expression of a natural product from the model
      marine actinomycete genus Salinispora. Using the recently developed method of
      yeast-mediated transformation-associated recombination for natural product gene
      clusters, we captured a type II polyketide synthase pathway from Salinispora
      pacifica with high homology to the enterocin pathway from Streptomyces maritimus
      and successfully produced enterocin in two different Streptomyces host strains.
      This result paves the way for the systematic interrogation of Salinispora's
      promising secondary metabolome.

PMID- 25382654
TI  - Synthesis and photoelectric properties of new Dawson-type polyoxometalate-based
      dimeric and oligomeric Pt(II)-acetylide inorganic-organic hybrids.
AB  - A new synthesis route for preparing Dawson-type polyoxometalate (POM) based
      inorganic-organic hybrid materials is presented. Two new heteropolytungstate
      based dimeric and oligomeric Pt(II) acetylide inorganic-organic hybrid compounds
      (2PtOD and PPtOD) were prepared by Hagihara's dehydrohalogenating coupling of a
      terminal diacetylene POM hybrid containing diphosphoryl functionality and an
      appropriate platinum(II) halide precursor. This method provides a rigid covalent
      linkage between the POM and the organometallic Pt(II) acetylide moiety. The redox
      potential of the polyanion can be tuned by grafting the organic and
      organometallic groups on it. The photoelectric properties of hybrid LB films
      derived from these inorganic-organic composites were studied.

PMID- 25382656
TI  - Hollow rhodoliths increase Svalbard's shelf biodiversity.
AB  - Rhodoliths are coralline red algal assemblages that commonly occur in marine
      habitats from the tropics to polar latitudes. They form rigid structures of high
      magnesium calcite and have a good fossil record. Here I show that rhodoliths are
      ecosystem engineers in a high Arctic environment that increase local biodiversity
      by providing habitat. Gouged by boring mussels, originally solid rhodoliths
      become hollow ecospheres intensely colonised by benthic organisms. In the
      examined shelf areas, biodiversity in rhodolith-bearing habitats is significantly
      greater than in habitats without rhodoliths and hollow rhodoliths yield a greater
      biodiversity than solid ones. This biodiversity, however, is threatened because
      hollow rhodoliths take a long time to form and are susceptible to global change
      and anthropogenic impacts such as trawl net fisheries that can destroy hollow
      rhodoliths. Rhodoliths and other forms of coralline red algae play a key role in
      a plurality of environments and need improved management and protection plans. 

PMID- 25382657
TI  - Graphene nano-floating gate transistor memory on plastic.
AB  - A transparent flexible graphene nano-floating gate transistor memory (NFGTM)
      device was developed by combining a single-layer graphene active channel with
      gold nanoparticle (AuNP) charge trap elements. We systematically controlled the
      sizes of the AuNPs, the thickness of the tunneling dielectric layer, and the
      graphene doping level. In particular, we propose that the conductance difference
      (i.e., memory window) between the programming and erasing operations at a
      specific read gate voltage can be maximized through the doping. The resulting
      graphene NFGTMs developed here exhibited excellent programmable memory
      performances compared to previously reported graphene memory devices and
      displayed a large memory window (12 V), fast switching speed (1 MUs), robust
      electrical reliability (10(5) s), and good mechanical (500 cycles) and thermal
      stability (100  degrees C). 

PMID- 25382655
TI  - Identification of candidate long noncoding RNAs associated with left ventricular
      hypertrophy.
AB  - PURPOSE: Long noncoding RNAs (lncRNAs) constitute an emerging group of noncoding
      RNAs, which regulate gene expression. Their role in cardiac disease is poorly
      known. Here, we investigated the association between lncRNAs and left ventricular
      hypertrophy. METHODS: Wild-type and adenosine A2A receptor overexpressing mice
      (A2A-Tg) were subjected to transverse aortic constriction (TAC) and expression of
      lncRNAs in the heart was investigated using genome-wide microarrays and an
      analytical pipeline specifically developed for lncRNAs. RESULTS: Microarray
      analysis identified two lncRNAs up-regulated and three down-regulated in the
      hearts of A2A-Tg mice subjected to TAC. Quantitative PCR showed that lncRNAs
      2900055J20Rik and Gm14005 were decreased in A2A-Tg mice (3.5- and 1.8-fold, p <
      0.01). We found from public microarray dataset that 2900055J20Rik and Gm14005
      were increased in TAC mice compared to sham-operated animals (1.8- and 1.4-fold,
      after 28 days, p < 0.01). Interestingly, in this public dataset, cardioprotective
      drug JQ1 decreased 2900055J20Rik and Gm14005 expression by 2.2- and 1.6-fold (p <
      0.01). CONCLUSIONS: First, we have shown that data on lncRNAs can be obtained
      from gene expression microarrays. Second, expression of lncRNAs 2900055J20Rik and
      Gm14005 is regulated after TAC and can be modulated by cardioprotective
      molecules. These observations motivate further investigation of the therapeutic
      value of lncRNAs in the heart.

PMID- 25382658
TI  - Immature dendritic cells convert anergic nonregulatory T cells into Foxp3- IL-10+
      regulatory T cells by engaging CD28 and CTLA-4.
AB  - Anergic T cells can survive for long time periods passively in a hyporesponsive
      state without obvious active functions. Thus, the immunological reason for their
      maintenance is unclear. Here, we induced peptide-specific anergy in T cells from
      mice by coculturing these cells with immature murine dendritic cells (DCs). We
      found that these anergic, nonsuppressive IL-10(-) Foxp3(-) CTLA-4(+) CD25(low)
      Egr2(+) T cells could be converted into suppressive IL-10(+) Foxp3(-) CTLA-4(+)
      CD25(high) Egr2(+) cells resembling type-1 Treg cells (Tr1) when stimulated a
      second time by immature DCs in vitro. Addition of TGF-beta during anergy
      induction favored Foxp3(+) Treg-cell induction, while TGF-beta had little effect
      when added to the second stimulation. Expression of both CD28 and CTLA-4
      molecules on anergic T cells was required to allow their conversion into Tr1-like
      cells. Suppressor activity was enabled via CD28-mediated CD25 upregulation,
      acting as an IL-2 sink, together with a CTLA-4-mediated inhibition of
      NFATc1/alpha activation to shut down IL-2-mediated proliferation. Together, these
      data provide evidence and mechanistical insights into how persistent anergic T
      cells may serve as a resting memory pool for Tr1-like cells. 

PMID- 25382659
TI  - Awareness of memory deficits in subjective cognitive decline, mild cognitive
      impairment, Alzheimer's disease and Parkinson's disease.
AB  - BACKGROUND: Impaired awareness of memory deficits has been recognized as a common
      phenomenon in Alzheimer's disease (AD) and research is now increasingly focusing
      on awareness in groups at risk for future dementia. This study aimed to determine
      whether levels of awareness differ among healthy elderly people and patients with
      subjective cognitive decline (SCD), amnestic and non-amnestic subtypes of mild
      cognitive impairment (aMCI, naMCI), Alzheimer's disease (AD) and Parkinson's
      disease (PD), to explore correlates of awareness and to establish frequencies of
      memory over- and underestimation within each diagnostic group. METHODS: 756
      consecutive outpatients of a memory clinic and 211 healthy controls underwent
      thorough neuropsychological testing. Impairment of awareness was measured as the
      difference between subjective memory appraisals (16-item questionnaire on current
      memory-related problems in everyday life) and objective memory performance (15
      item delayed recall task). Subgroups of over- and underestimators were classified
      using percentile ranks of controls. RESULTS: At group level, awareness
      significantly decreased along the naMCI->aMCI->AD continuum, with naMCI patients
      showing a tendency towards overestimation of memory dysfunction. PD patients
      showed accurate self-appraisals as long as memory function was largely
      unaffected. However, there was a considerable between-group overlap in awareness
      scores. Furthermore, different correlates of awareness were observed depending on
      the diagnostic group. In general, unawareness seems to be associated with
      decreased cognitive performance in various domains (especially memory), higher
      age and lower levels of depression and self-reported functional impairment.
      CONCLUSION: Impaired awareness is an important symptom in aMCI. Yet, given the
      considerable variability in awareness scores, longitudinal studies are required
      to evaluate their predictive power.

PMID- 25382661
TI  - Linking winter conditions to regional disease dynamics in a wild plant-pathogen
      metapopulation.
AB  - Pathogens are considered to drive ecological and evolutionary dynamics of plant
      populations, but we lack data measuring the population-level consequences of
      infection in wild plant-pathogen interactions. Moreover, while it is often
      assumed that offseason environmental conditions drive seasonal declines in
      pathogen population size, little is known about how offseason environmental
      conditions impact the survival of pathogen resting stages, and how critical the
      offseason is for the next season's epidemic. The fungal pathogen Podosphaera
      plantaginis persists as a dynamic metapopulation in the large network of Plantago
      lanceolata host populations. Here, we analyze long-term data to measure the
      spatial synchrony of epidemics and consequences of infection for over 4000 host
      populations. Using a theoretical model, we study whether large-scale
      environmental change could synchronize disease occurrence across the
      metapopulation. During 2001-2013 exposure to freezing decreased, while pathogen
      extinction-colonization-persistence rates became more synchronized. Simulations
      of a theoretical model suggest that increasingly favorable winter conditions for
      pathogen survival could drive such synchronization. Our data also show that
      infection decreases host population growth. These results confirm that mild
      winter conditions increase pathogen overwintering success and thus increase
      disease prevalence across the metapopulation. Further, we conclude that the
      pathogen can drive host population growth in the Plantago-Podosphaera system. 

PMID- 25382660
TI  - The mTORC1 effectors S6K1 and 4E-BP play different roles in CNS axon
      regeneration.
AB  - Using mouse optic nerve (ON) crush as a CNS injury model, we and others have
      found that activation of the mammalian target of rapamycin complex 1 (mTORC1) in
      mature retinal ganglion cells by deletion of the negative regulators, phosphatase
      and tensin homologue (PTEN), and tuberous sclerosis 1 promotes ON regeneration.
      mTORC1 activation inhibits eukaryotic translation initiation factor 4E-binding
      protein (4E-BP) and activates ribosomal protein S6 kinase 1 (S6K1), both of which
      stimulate translation. We reasoned that mTORC1's regeneration-promoting effects
      might be separable from its deleterious effects by differential manipulation of
      its downstream effectors. Here we show that S6K1 activation, but not 4E-BP
      inhibition, is sufficient to promote axon regeneration. However, inhibition of 4E
      BP is required for PTEN deletion-induced axon regeneration. Both activation and
      inhibition of S6K1 decrease the effect of PTEN deletion on axon regeneration,
      implicating a dual role of S6K1 in regulating axon growth. 

PMID- 25382662
TI  - A case-control study evaluating the relationship between thimerosal-containing
      haemophilus influenzae type b vaccine administration and the risk for a pervasive
      developmental disorder diagnosis in the United States.
AB  - Thimerosal is an organic mercury (Hg)-containing compound (49.55 % Hg by weight)
      historically added to many multi-dose vials of vaccine as a preservative. A
      hypothesis testing case-control study evaluated automated medical records in the
      Vaccine Safety Datalink (VSD) for organic Hg exposure from Thimerosal in
      Haemophilus influenzae type b (Hib)-containing vaccines administered at specific
      times within the first 15 months of life among subjects diagnosed with pervasive
      developmental disorder (PDD) (n = 534) in comparison to controls. The generally
      accepted biologically non-plausible linkage between Thimerosal exposure and
      subsequent diagnosis of febrile seizure (n = 5886) was examined as a control
      outcome. Cases diagnosed with PDD received significantly more organic Hg within
      the first 6 months of life (odds ratio (OR) = 1.97, p < 0.001) and first 15
      months of life (OR = 3.94, p < 0.0001) than controls, whereas cases diagnosed
      with febrile seizure were no more likely than controls to have received increased
      organic Hg. On a per microgram of organic Hg basis, cases diagnosed with a PDD in
      comparison to controls were at significantly greater odds (OR = 1.0197, p <
      0.0001) of receiving increasing organic Hg exposure within the first 15 months of
      life, whereas cases diagnosed febrile seizure were no more likely than controls
      (OR = 0.999, p > 0.20) to have received increasing organic Hg exposure within the
      first 15 months of life. Routine childhood vaccination is an important public
      health tool to reduce the morbidity and mortality associated with infectious
      diseases, but the present study provides new epidemiological evidence of a
      significant relationship between increasing organic Hg exposure from Thimerosal
      containing vaccines and the subsequent risk of PDD diagnosis in males and
      females. 

PMID- 25382663
TI  - Menopause and blood mercury levels: the Korea National Health and Nutrition
      Examination Survey (KNHANES) 2008-2011.
AB  - This study aimed to evaluate the association between menopause and blood mercury
      concentrations in South Korean women. Women aged >=20 years who participated in
      the Korean National Health and Nutrition Examination Survey 2008-2011 were
      included in this study. Primary and secondary analyses included women aged >=20
      years (n = 1,642) and 45-55 years (i.e., perimenopausal; n = 325), respectively.
      For all analyses, the mercury levels were log-transformed. The linear regression
      model for mercury levels was adjusted for age, body mass index, household income,
      menopausal status, hormone replacement therapy, use of oral contraceptives,
      smoking history, alcohol intake, physical activity, number of pregnancies, serum
      ferritin levels, and fish consumption. After adjusting for covariates, log
      transformed blood mercury levels were significantly lower in women who were
      menopausal [beta-coefficient -0.1488; 95 % confidence interval -0.2586, -0.0389;
      P = 0.01) than in those who were premenopausal. A similar relationship was
      identified in perimenopausal women (beta-coefficient -0.1753; 95 % confidence
      interval -0.3357, -0.015; P = 0.03). The blood mercury concentration was lower in
      postmenopausal women than in premenopausal women. There was a significant
      positive correlation between blood mercury concentrations and both the frequency
      of alcohol intake and serum ferritin levels.

PMID- 25382664
TI  - Enantioselective synthesis of alpha-secondary and alpha-tertiary piperazin-2-ones
      and piperazines by catalytic asymmetric allylic alkylation.
AB  - The asymmetric palladium-catalyzed decarboxylative allylic alkylation of
      differentially N-protected piperazin-2-ones allows the synthesis of a variety of
      highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction
      affords the corresponding tertiary piperazines, which can be employed for the
      synthesis of medicinally important analogues. The introduction of these chiral
      tertiary piperazines resulted in imatinib analogues which exhibited comparable
      antiproliferative activity to that of their corresponding imatinib counterparts. 

PMID- 25382666
TI  - Origin of the enantioselectivity in organocatalytic Michael additions of beta
      ketoamides to alpha,beta-unsaturated carbonyls: a combined experimental,
      spectroscopic and theoretical study.
AB  - The organocatalytic enantioselective conjugate addition of secondary beta
      ketoamides to alpha,beta-unsaturated carbonyl compounds is reported. Use of
      bifunctional Takemoto's thiourea catalyst allows enantiocontrol of the reaction
      leading either to simple Michael adducts or spirocyclic aminals in up to 99 % ee.
      The origin of the enantioselectivity has been rationalised based on combined DFT
      calculations and kinetic analysis. This study provides a deeper understanding of
      the reaction mechanism, which involves a predominant role of the secondary amide
      proton, and clarifies the complex interactions occurring between substrates and
      the catalyst. 

PMID- 25382667
TI  - In situ transmission electron microscopy of ionic conductivity and reaction
      mechanisms in ultrathin solid oxide fuel cells.
AB  - Solid oxide fuel cells (SOFCs) are promising candidates for use in alternative
      energy technologies. A full understanding of the reaction mechanisms in these
      dynamic material systems is required to optimize device performance and overcome
      present limitations. Here, we show that in situ transmission electron microscopy
      (TEM) can be used to study redox reactions and ionic conductivity in SOFCs in a
      gas environment at elevated temperature. We examine model ultrathin half and
      complete cells in two environmental TEMs using off-axis electron holography and
      electron energy-loss spectroscopy. Our results from the model cells provide
      insight into the essential phenomena that are important for the operation of
      commercial devices. Changes in the activities of dopant cations in the solid
      electrolyte are detected during oxygen anion conduction, demonstrating the key
      role of dopants in electrolyte architecture in SOFCs. 

PMID- 25382665
TI  - Clinical outcomes of splenectomy in children: report of the splenectomy in
      congenital hemolytic anemia registry.
AB  - The outcomes of children with congenital hemolytic anemia (CHA) undergoing total
      splenectomy (TS) or partial splenectomy (PS) remain unclear. In this study, we
      collected data from 100 children with CHA who underwent TS or PS from 2005 to
      2013 at 16 sites in the Splenectomy in Congenital Hemolytic Anemia (SICHA)
      consortium using a patient registry. We analyzed demographics and baseline
      clinical status, operative details, and outcomes at 4, 24, and 52 weeks after
      surgery. Results were summarized as hematologic outcomes, short-term adverse
      events (AEs) (<=30 days after surgery), and long-term AEs (31-365 days after
      surgery). For children with hereditary spherocytosis, after surgery there was an
      increase in hemoglobin (baseline 10.1 +/- 1.8 g/dl, 52 week 12.8 +/- 1.6 g/dl;
      mean +/- SD), decrease in reticulocyte and bilirubin as well as control of
      symptoms. Children with sickle cell disease had control of clinical symptoms
      after surgery, but had no change in hematologic parameters. There was an 11% rate
      of short-term AEs and 11% rate of long-term AEs. As we accumulate more subjects
      and longer follow-up, use of a patient registry should enhance our capacity for
      clinical trials and engage all stakeholders in the decision-making process.

PMID- 25382668
TI  - 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin induces premature senescence of astrocytes
      via WNT/beta-catenin signaling and ROS production.
AB  - 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental
      contaminant that could exert significant neurotoxicity in the human nervous
      system. Nevertheless, the molecular mechanism underlying TCDD-mediated
      neurotoxicity has not been clarified clearly. Herein, we investigated the
      potential role of TCDD in facilitating premature senescence in astrocytes and the
      underlying molecular mechanisms. Using the senescence-associated beta
      galactosidase (SA-beta-Gal) assay, we demonstrated that TCDD exposure triggered
      significant premature senescence of astrocyte cells, which was accompanied by a
      marked activation of the Wingless and int (WNT)/beta-catenin signaling pathway.
      In addition, TCDD altered the expression of senescence marker proteins, such as
      p16, p21 and GFAP, which together have been reported to be upregulated in aging
      astrocytes, in both dose- and time-dependent manners. Further, TCDD led to cell
      cycle arrest, F-actin reorganization and the accumulation of cellular reactive
      oxygen species (ROS). Moreover, the ROS scavenger N-acetylcysteine (NAC) markedly
      attenuated TCDD-induced ROS production, cellular oxidative damage and astrocyte
      senescence. Notably, the application of XAV939, an inhibitor of WNT/beta-catenin
      signaling pathway, ameliorated the effect of TCDD on cellular beta-catenin level,
      ROS production, cellular oxidative damage and premature senescence in astrocytes.
      In summary, our findings indicated that TCDD might induce astrocyte senescence
      via WNT/beta-catenin and ROS-dependent mechanisms.

PMID- 25382669
TI  - Tumors of the neural crest: Common themes in development and cancer.
AB  - The neural crest (NC) is a remarkable transient structure in the vertebrate
      embryo that gives rise to a highly versatile population of pluripotent cells that
      contribute to the formation of multiple tissues and organs throughout the body.
      In order to achieve their task, NC-derived cells have developed specialized
      mechanisms to promote (1) their transition from an epithelial to a mesenchymal
      phenotype, (2) their capacity for extensive migration and cell proliferation, and
      (3) their ability to produce diverse cell types largely depending on the
      microenvironment encountered during and after their migratory path. Following
      embryogenesis, these same features of cellular motility, invasion, and
      proliferation can become a liability by contributing to tumorigenesis and
      metastasis. Ample evidence has shown that cancer cells have cleverly co-opted
      many of the genetic and molecular features used by developing NC cells. This
      review focuses on tumors that arise from NC-derived tissues and examines
      mechanistic themes shared during their oncogenic and metastatic development with
      embryonic NC cell ontogeny.

PMID- 25382670
TI  - Why we think we can't dance: theory of mind and children's desire to perform.
AB  - Theory of mind (ToM) allows children to achieve success in the social world by
      understanding others' minds. A study with 3- to 12-year-olds, however,
      demonstrates that gains in ToM are linked to decreases in children's desire to
      engage in performative behaviors associated with health and well-being, such as
      singing and dancing. One hundred and fifty-nine middle-class children from
      diverse backgrounds in a Northeastern U.S. metropolitan area completed the study
      in 2011. The development of ToM is associated with decreases in self-esteem,
      which in turn predicts decreases in children's willingness to perform. This shift
      away from performance begins at age 4 (when ToM begins to develop), years before
      children enter puberty. 

PMID- 25382673
TI  - Quantification of blood loss: AWHONN practice brief number 1.

PMID- 25382672
TI  - Differential methylation of the promoter and first exon of the RASSF1A gene in
      hepatocarcinogenesis.
AB  - AIM: Aberrant methylation of the promoter, P2, and the first exon, E1, regions of
      the tumor suppressor gene RASSF1A, have been associated with hepatocellular
      carcinoma (HCC), albeit with poor specificity. This study analyzed the
      methylation profiles of P1, P2 and E1 regions of the gene to identify the region
      of which methylation most specifically corresponds to HCC and to evaluate the
      potential of this methylated region as a biomarker in urine for HCC screening.
      METHODS: Bisulfite DNA sequencing and quantitative methylation-specific
      polymerase chain reaction assays were performed to compare methylation of the 56
      CpG sites in regions P1, P2 and E1 in DNA isolated from normal, hepatitic,
      cirrhotic, adjacent non-HCC, and HCC liver tissue and urine samples for the
      characterization of hypermethylation of the RASSF1A gene as a biomarker for HCC
      screening. RESULTS: In tissue, comparing HCC (n = 120) with cirrhosis and
      hepatitis together (n = 70), methylation of P1 had an area under the receiver
      operating characteristics curve (AUROC) of 0.90, whereas methylation of E1 and P2
      had AUROC of 0.84 and 0.72, respectively. At 90% sensitivity, specificity for P1
      methylation was 72.9% versus 38.6% for E1 and 27.1% for P2. Methylated P1 DNA was
      detected in urine in association with cirrhosis and HCC. It had a sensitivity of
      81.8% for alpha-fetoprotein negative HCC. CONCLUSION: Among the three regions
      analyzed, methylation of P1 is the most specific for HCC and holds great promise
      as a DNA marker in urine for screening of cirrhosis and HCC.

PMID- 25382674
TI  - Vasomotor symptoms and urogenital atrophy in older women: a systematic review.
AB  - OBJECTIVE: Our aim was to systematically review published articles for the
      prevalence of persistent estrogen depletion symptoms among women aged 65+ years.
      METHODS: A systematic literature search of English-language publications was
      performed using MEDLINE, EMBASE, CINAHL, and PsycINFO. Twenty-three studies that
      included information on the prevalence of vasomotor and/or urogenital atrophy
      symptoms among older women (65 + years) met our inclusion criteria. Risk of bias
      of the included studies was assessed using a risk-of-bias tool explicitly
      designed for the systematic review of prevalence studies. RESULTS: The available
      data suggest that vasomotor symptoms are experienced by a considerable proportion
      of older women, that symptoms of urogenital atrophy including urinary
      incontinence are widespread, and that women remain sexually active well into
      later life. A high degree of variability was observed for the prevalence of
      estrogen deficiency symptoms for women age 65+ years. Discrepancies in modes of
      recruitment, sampling procedures, time frames over which symptoms were assessed
      and use of different and non-validated assessment tools contributed to the
      inconsistencies across the published studies. CONCLUSION: Larger and
      appropriately sampled studies, employing validated questionnaires, are still
      needed to establish the prevalence of persistent estrogen depletion symptoms in
      women aged 65+ years.

PMID- 25382675
TI  - Towards high-level theoretical studies of large biodiesel molecules: an ONIOM
      [QCISD(T)/CBS:DFT] study of hydrogen abstraction reactions of
      C(n)H(2n+1)COOC(m)H(2m+1) + H.
AB  - Recent interest in biodiesel combustion urges the need for the theoretical
      chemical kinetics of large alkyl ester molecules. This is, however,
      computationally challenging for prevalent high-level electronic structure theory
      based methods. The hydrogen abstraction reactions of alky esters
      CnH2n+1COOCmH2m+1 (n = 1-5, 9, 15; m = 1, 2) by a hydrogen radical were
      investigated by a computational technique based on a two-layer ONIOM method,
      employing a QCISD(T)/CBS method for the high layer and a DFT method for the low
      layer. The calculated energy barriers and heats of reaction, using the ONIOM
      method with a minimum of the required chemically active portion, are in very good
      agreement with those obtained using the widely accepted high-level QCISD(T)/CBS
      theory because the computational errors were less than 0.1 kcal mol(-1) for all
      the tested cases. The ONIOM[QCISD(T)/CBS:DFT] method provides a computationally
      accurate and affordable approach to the high-level theoretical chemical kinetics
      of large biodiesel molecules. 

PMID- 25382676
TI  - Effect of diabetes on scintigraphic infarct size in STEMI patients undergoing
      primary angioplasty.
AB  - BACKGROUND: It has been shown that among patients with ST-segment elevation
      myocardial infarction (STEMI), diabetes is associated with a significantly higher
      mortality, mainly because of impaired reperfusion. However, few data have been
      reported so far on infarct size as evaluated by well-refined techniques, such as
      nuclear imaging techniques. Therefore, the aim of the current study was to
      investigate the effect of diabetes in infarct size as evaluated by myocardial
      scintigraphy in a large cohort of STEMI patients undergoing primary PCI. METHODS:
      We included 830 STEMI patients undergoing primary PCI. Infarct size was evaluated
      at 30 days by technetium-99 m-sestamibi. A logistic regression analysis was
      performed to determine the relation between diabetes and infarct size (as above
      the median) after correction for baseline confounding factors. RESULTS: A total
      of 115 (13.8%) out of 830 patients suffered from diabetes. Diabetic patients were
      older (p < 0.001), with larger prevalence of female gender (p = 0.006) and
      hypertension (p = 0.001) but were less often smokers (p = 0.003). Diabetic
      patients had more often preprocedural thrombolysis in myocardial infarction grade
      3 flow (p = 0.034) and less complete ST-segment resolution (p = 0.009). No
      difference was observed in scintigraphic infarct size between diabetes and
      control patients (p = 0.6)), which was confirmed at multivariate analysis after
      correction for baseline confounding factors (Adjusted OR [95% CI] = 0.87 [0.57
      1.31, p = 0.51). CONCLUSION: Our study showed that among STEMI patients
      undergoing primary angioplasty, diabetes did not affect infarct size as compared
      with non-diabetic patients.

PMID- 25382677
TI  - Cell- and biomarker-based assays for predicting nephrotoxicity.
AB  - INTRODUCTION: Drug-induced nephrotoxicity contributes to the failure rate of
      investigational drugs during clinical trials. We are still not able to accurately
      predict drug-induced nephrotoxicity during early drug discovery and development.
      There is an urgent need for a robust screening system that can identify
      nephrotoxic compounds before they reach the clinic. AREAS COVERED: This review
      discusses traditional and emerging kidney injury biomarkers that are used for the
      determination of nephrotoxicity and for evaluation and diagnosis of other kidney
      diseases. The potential for in vivo biomarkers to predict renal toxicity in high
      throughput in vitro screening assays is discussed. We also compare cell types and
      highlight novel three-dimensional (3D) culture technologies with potential for in
      vitro prediction of nephrotoxicity. EXPERT OPINION: Traditional cell culture
      methods and cytotoxicity assays are well established as in vitro tests for
      nephrotoxicity but the correlation with in vivo results is extremely poor.
      Recently validated renal biomarkers show promise for early in vivo detection of
      nephrotoxicity, but have yet to be successfully applied for in vitro prediction
      of drug-induced nephrotoxicity. Advanced culture technologies 'kidney-on-a-chip'
      and 3D culture can produce biomarker signatures from relevant kidney cell types
      that show promise as better predictive systems.

PMID- 25382678
TI  - Reactivity of bulky formamidinatosamarium(II or III) complexes with C?O and C?S
      bonds.
AB  - The preparation of a new heterobimetallic samarium(II) formamidinate complex and
      selected reactions of samarium(II) complexes and one samarium(III) formamidinate
      complex with benzophenone or CS2 are discussed. Treatment of the
      tris(formamidinato)samarium(III) complex [Sm(DippForm)3] 1 (DippForm = N,N'
      bis(2,6-diisopropylphenyl)formamidinate, (CH(NC6H3-(i)Pr2-2,6)2) with potassium
      graphite in toluene yielded the dark brown heterobimetallic
      formamidinatosamarium(II)/potassium complex [KSm(DippForm)3]n 2. Divalent 2, a
      Lewis base solvent free homoleptic species, differs significantly from the
      related heteroleptic formamidinatosamarium(II) complex [Sm(DippForm)2(thf)2] 3
      with respect to its constitution, structure, and reactivity toward benzophenone.
      While 2 reacts giving complex 1, the reaction of 3 with benzophenone generates
      the highly unusual [Sm(DippForm)2(thf){MU-OC(Ph)?(C6H5)C(Ph)2O}Sm(DippForm)2]
      (C6H5 = 1,4-cyclohexadiene-3-yl-6-ylidene) 4. The formation of 4 highlights a
      rare C-C coupling between a carbonyl carbon and the carbon at the para position
      of a phenyl group of the OCPh2 fragment. An analogous reaction of
      [Yb(DippForm)2(thf)2] gives an isostructural complex 4Yb. 3 reacts with carbon
      disulfide forming a light green dinuclear formamidinatosamarium(III) complex
      [{Sm(DippForm)2(thf)}2(MU-eta(2)(C,S):kappa(S',S")-SCSCS2)] 5 through an unusual
      C-S coupling induced by an amidinatolanthanoid species giving the
      thioformylcarbonotrithioate ligand. The trivalent organometallic
      [Sm(DippForm)2(CCPh)(thf)] complex activates the C?O bond of benzophenone by an
      insertion reaction, forming the light yellow [Sm(DippForm)2{OC(Ph)2C2Ph}(thf)] 6
      as a major product and light yellow unsolvated [Sm(DippForm)2{OC(Ph)2C2Ph}] 7 as
      a minor product. Molecular structures of complexes (2, 4-7) show that kappa(N,N')
      bonding between a DippForm and samarium atom exists in all compounds, but in 2,
      DippForm also bridges K and Sm by 1kappa(N):2kappa(N') bonding and two 2,6
      diisopropylphenyl groups are eta(6)-bonded to potassium. 

PMID- 25382679
TI  - Sex determination by discriminant function analysis of lumbar vertebrae.
AB  - Sex determination is critical for developing the biological profile of
      unidentified skeletal remains. When more commonly used elements (os coxa,
      cranium) for sexing are not available, methods utilizing other skeletal elements
      are needed. This study aims to assess the degree of sexual dimorphism of the
      lumbar vertebrae and develop discriminant functions for sex determination from
      them, using a sample of South African blacks from the Raymond A. Dart Collection
      (47 males, 51 females). Eleven variables at each lumbar level were subjected to
      univariate and multivariate discriminant function analyses. Univariate equations
      produced classification rates ranging from 57.7% to 83.5%, with the highest
      accuracies associated with dimensions of the vertebral body. Multivariate
      stepwise analysis generated classification rates ranging from 75.9% to 88.7%.
      These results are comparable to other methods for sexing the skeleton and
      indicate that measures of the lumbar vertebrae can be used as an effective tool
      for sex determination. 

PMID- 25382680
TI  - Transcription factor CREB is involved in CaSR-mediated cytoskeleton gene
      expression.
AB  - Our previous studies illustrated that a steady increase of intracellular calcium
      concentration ([Ca2+]i) was important for maintaining microtubules (MTs)
      rearrangement in apoptotic cells. However, little is known about the effect of
      calcium sensing receptor (CaSR)-mediated increase in [Ca2+]i on cytoskeleton gene
      expression. We examined the impact of taxol or CaSR agonist/antagonist on the
      regulation of [Ca2+]i concentration, cytoskeleton arrangement, phosphorylated
      CREB and cytoskeleton gene expressions in HeLa cells with dominant negative
      plasmid of CREB (PM). This study demonstrated that Gdcl3 (a specific CaSR
      agonist) evoked a rapid increase of [Ca2+]i, formed a rigid bundle of MTs which
      surrounded the nucleus and decreased the cytoskeleton gene expressions in HeLa
      cells. These effects were rescued by addition of NPS2390 (a specific CaSR
      antagonist). Moreover, CaSR activity affected cytoskeleton gene expression
      through transcription factor CREB. Histoscores of pCREB immunoreactivity in
      tissues of cervical adenocarcinoma, renal clear cell carcinoma, and diffuse large
      B-cell lymphoma were markedly increased compared with non malignant tissue. These
      data demonstrate, for the first time, that CaSR-mediated increase in [Ca2+]i
      probably modulate cytoskeleton organization and gene expression via transcription
      factor.

PMID- 25382681
TI  - 'Looking like a bad person': vocabulary of motives and narrative analysis in a
      story of nursing collegiality.
AB  - Collegiality among nurses is necessary for the accomplishment of the tasks of
      care, for safety and quality improvement and for professional self-regulation.
      Nurses, especially in hospitals, are more likely to work in groups than other
      professionals, yet those relationships have not been well explored. Bullying,
      intimidation and fear are frequently identified, while respectful disagreements
      are rarely described. In this paper, a single story by a nurse about her
      conversational conflict with another nurse is given a close reading. I use the
      'triadic line' of William Carlos Williams to format an extended excerpt of
      interview text, in order to make visible the rhythms and organization of spoken
      language. Mills' concept of a 'vocabulary of motives' is used to examine the
      rhetorical strategies deployed by each nurse. Finally, I analyze the narrative
      structure of the story, highlighting the ways that moral certainty and
      uncertainty function to involve the reader in the story, and the complex role of
      virtue in nursing discourse. 

PMID- 25382682
TI  - Cerebral blood flow and cognitive function in patients with metabolic syndrome:
      effect of antihypertensive therapy.
AB  - The aim of the study was to estimate regional cerebral blood flow (rCBF) and
      cognitive function in patients with metabolic syndrome (MetS) before and after
      antihypertensive combination therapy. The study included 24 patients with MetS
      (average age 52.4+/-1.6 years). All patients underwent brain single-photon
      emission computed tomography with technetium-99m hexamethylpropyleneamine oxime
      and comprehensive neuropsychological testing before and after 6-month
      antihypertensive combination therapy. All patients with MetS showed lower rCBF
      values in all regions of the brain compared with the control group. Their
      parameters of attention, immediate visual memory, and mentation were lower by
      25%, 22%, and 13% compared with the control group, respectively. Six-month
      antihypertensive combination therapy increased cerebral perfusion and improved
      attention, mentation, and visual memory in MetS patients. 

PMID- 25382683
TI  - Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients
      exposed to perfluorinated compounds.
AB  - This study investigated chromosomal aneuploidies and DNA damage in spermatozoa
      from male patients contaminated by perfluorinated compounds (PFCs) in whole blood
      and seminal plasma. Sperm aneuploidy and diploidy rate for chromosomes 18, X and
      Y were evaluated by FISH; sperm DNA fragmentation was assessed by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labelling technique coupled
      to flow cytometry. Our results indicated that PFC contamination was present in
      58% of subjects included in the study. A significant increase in alterations of
      sperm parameters was observed in PFC-positive subjects compared to PFC-negative
      subjects. As regards the sperm aneuploidy, both disomy and diploidy rates
      resulted significantly increased in subjects positive for PFC contamination
      compared to PFC-negative samples. In addition, sperm DNA fragmentation index
      resulted significantly increased in PFC-contaminated subjects compared to PFC-non
      contaminated subjects, with a significant increased level of dimmer DNA
      fragmentation index. Our results clearly indicate that PFC contamination may
      detrimentally affect spermatogenesis, disturbing both meiotic segregation and DNA
      integrity. We could therefore suggest cautions to reduce or eliminate any contact
      with these compounds because the long-term effects of PFC accumulation in the
      body are not predictable.

PMID- 25382684
TI  - Role of occupational health in managing non-communicable diseases in Brunei
      Darussalam.
AB  - Like most ASEAN countries, Brunei faces an epidemic of non-communicable diseases.
      To deal with the complexity of NCDs prevention, all perspectives--be it social,
      familial or occupational--need to be considered. In Brunei Darussalam,
      occupational health services (OHS) offered by its Ministry of Health, among
      others, provide screening and management of NCDs at various points of service.
      The OHS does not only issue fitness to work certificates, but is a significant
      partner in co-managing patients' health conditions, with the advantage of further
      management at the workplace. Holistic approach of NCD management in the
      occupational setting is strengthened with both employer and employee education
      and participation, targeting several approaches including risk management and
      advocating healthy lifestyles as part of a healthy workplace programme.

PMID- 25382685
TI  - Addressing Ebola-related stigma: lessons learned from HIV/AIDS.
AB  - BACKGROUND: HIV/AIDS and Ebola Virus Disease (EVD) are contemporary epidemics
      associated with significant social stigma in which communities affected suffer
      from social rejection, violence, and diminished quality of life. OBJECTIVE: To
      compare and contrast stigma related to HIV/AIDS and EVD, and strategically think
      how lessons learned from HIV stigma can be applied to the current EVD epidemic.
      METHODS: To identify relevant articles about HIV/AIDS and EVD-related stigma, we
      conducted an extensive literature review using multiple search engines. PubMed
      was used to search for relevant peer-reviewed journal articles and Google for
      online sources. We also consulted the websites of the World Health Organization
      (WHO), Centers for Disease Control and Prevention (CDC), and the National
      Institutes of Health to retrieve up-to-date information about EVD and HIV/AIDS.
      RESULTS: Many stigmatizing attitudes and behaviors directed towards those with
      EVD are strikingly similar to those with HIV/AIDS but there are significant
      differences worthy of discussion. Both diseases are life-threatening and there is
      no medical cure. Additionally misinformation about affected groups and modes of
      transmission runs rampant. Unlike in persons with EVD, historically criminalized
      and marginalized populations carry a disproportionately higher risk for HIV
      infection. Moreover, mortality due to EVD occurs within a shorter time span as
      compared to HIV/AIDS. CONCLUSIONS: Stigma disrupts quality of life, whether it is
      associated with HIV infection or EVD. When addressing EVD, we must think beyond
      the immediate clinical therapeutic response, to possible HIV implications of
      serum treatment. There are emerging social concerns of stigma associated with EVD
      infection and double stigma associated with EVD and HIV infection. Drawing upon
      lessons learned from HIV, we must work to empower and mobilize prominent members
      of the community, those who recovered from the disease, and organizations working
      at the grassroots level to disseminate clear and accurate information about EVD
      transmission and prevention while promoting stigma reduction in the process. In
      the long run, education, prevention, and a therapeutic vaccine will be the
      optimal solutions for reducing the stigma associated with both EVD and HIV.

PMID- 25382686
TI  - Oxidant-based anticancer activity of a novel synthetic analogue of capsaicin,
      capsaicin epoxide.
AB  - OBJECTIVES: Plant-derived natural substances, such as capsaicin, with potent
      antiproliferative activity against cancer cells in vitro are considered to be
      promising nutraceuticals in anticancer therapy. Nevertheless, the limited
      systemic bioavailability of phytochemicals may raise questions regarding the
      physiological relevance of their phytochemical effects in vivo. Thus, the search
      for novel phytochemical-based substances with more efficient anticancer action is
      needed. METHODS: In the present study, a capsaicin analogue, namely, capsaicin
      epoxide, was synthesized, and its cytotoxic potential against cancer cells was
      evaluated and compared to that of capsaicin through 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) and multi-caspase assays. The abilities of
      capsaicin and capsaicin epoxide to induce oxidative stress were estimated using
      redox-sensitive fluorogenic probes: 2',7'-dichlorodihydrofluorescein diacetate
      (H2DCF-DA) and dihydroethidium. RESULTS: The structure and purity of the
      synthesized product were confirmed by nuclear magnetic resonance spectroscopy,
      electrospray ionization mass spectrometry, and gas chromatography. Normal human
      dermal fibroblasts were not susceptible to treatment with the agent, whereas a
      cancer cell type-specific response was observed. Human breast carcinoma cells
      were found to be the most sensitive to capsaicin epoxide treatment compared with
      capsaicin treatment, and the action of capsaicin epoxide was oxidant based.
      DISCUSSION: Our data indicate that the antiproliferative activity of capsaicin
      epoxide is potentiated in vitro, when used at much lower concentrations compared
      with capsaicin at similar concentrations. Thus, the findings of this study may
      have implications for phytochemical-based anticancer drug development.

PMID- 25382688
TI  - Enantioselective construction of vicinal tetrasubstituted stereocenters by the
      mannich reaction of silyl ketene imines with isatin-derived ketimines.
AB  - A highly enantioselective Mannich reaction of silyl ketene imines with isatin
      derived ketimines has been realized by using a chiral N,N'-dioxide/Zn(II)
      catalyst. A variety of beta-amino nitriles containing congested vicinal
      tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 %
      yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a
      possible transition state has been proposed to explain the origin of the
      asymmetric induction. 

PMID- 25382687
TI  - Oligomerization of FtsZ converts the FtsZ tail motif (conserved carboxy-terminal
      peptide) into a multivalent ligand with high avidity for partners ZipA and SlmA.
AB  - A short conserved motif located at the carboxy terminus of FtsZ, referred to here
      as the CCTP (conserved carboxy-terminal peptide), is required for the interaction
      of FtsZ with many of its partners. In Escherichia coli interaction of FtsZ with
      its membrane anchors, ZipA and FtsA, as well as the spatial regulators of Z-ring
      formation, MinC and SlmA, requires the CCTP. ZipA interacts with FtsZ with high
      affinity and interacts with the CCTP with low affinity, but the reason for this
      difference is not clear. In this study, we show that this difference is due to
      the oligomerization of FtsZ converting the CCTP to a multivalent ligand that
      binds multiple ZipAs bound to a surface with high avidity. Artificial
      dimerization of the CCTP is sufficient to increase the affinity for ZipA in
      vitro. Similar principles apply to the interaction of FtsZ with SlmA. Although
      done in vitro, these results have implications for the recruitment of FtsZ to the
      membrane in vivo, the interaction of FtsZ with spatial regulators and the
      reconstitution of FtsZ systems in vitro. 

PMID- 25382689
TI  - An acidic pectin lyase from Aspergillus niger with favourable efficiency in fruit
      juice clarification.
AB  - The pectin lyase gene pnl-zj5a from Aspergillus niger ZJ5 was identified and
      expressed in Pichia pastoris. PNL-ZJ5A was purified by ultrafiltration, anion
      exchange and gel chromatography. The Km and Vmax values determined using citrus
      pectin were 0.66 mg ml(-1) and 32.6 MUmol min(-1) mg(-1) , respectively. PNL-ZJ5A
      exhibited optimal activity at 43 degrees C and retained activity over 25-50
      degrees C. PNL-ZJ5A was optimally active at pH 5 and effective in apple juice
      clarification. Compared with controls, PNL-ZJ5A increased the fruit juice yield
      significantly. Furthermore, PNL-ZJ5A reduced the viscosity of apple juice by
      38.8% and increased its transmittance by 86.3%. PNL-ZJ5A combined with a
      commercial pectin esterase resulted in higher juice volume.

PMID- 25382690
TI  - Bevacizumab for symptomatic radiation-induced tumor enlargement in pediatric low
      grade gliomas.
AB  - BACKGROUND: Radiation therapy (RT)-induced effects in children treated for low
      grade glioma (LGG) can result in worsening of neurologic symptoms and clinical
      and radiographic deterioration. Treatment for radiation-induced tumor enlargement
      is based on symptom control and usually involves steroids. PROCEDURE: We
      conducted a retrospective review of children with LGG treated with RT who
      developed symptomatic radiation-induced tumor enlargement and were managed with
      bevacizumab. Charts were abstracted for onset and duration of RT changes,
      toxicity and doses of dexamethasone and bevacizumab. Tumor volumes prior to RT,
      at maximal size following RT, after bevacizumab administration, and at follow-up
      were evaluated. RESULTS: Five children were treated with bevacizumab for
      symptomatic radiation-induced tumor enlargement following RT for LGG at a median
      of 4.2 months (range, 1-11 months) after completion of RT. The median increase in
      volume of tumor was 195.4% (range, 115.5-309%) compared to the pre-RT volume.
      Bevacizumab 5-10 mg/kg was administered IV q 2-4 weeks as primary treatment (n =
      1) or to assist in weaning patients off steroids (n = 4). All children on high
      dose steroids (n = 4) were weaned off or to physiologic doses of hydrocortisone.
      Two children developed avascular necrosis after prolonged steroid use and while
      on bevacizumab. Radiographically, all children showed significant improvement and
      are now a median of 31 months (range, 18-50 months) from the completion of
      radiation without requiring additional tumor-related therapy. CONCLUSIONS:
      Bevacizumab can play an important role in children with symptomatic radiation
      changes following LGG treatment, allowing patients to avoid or minimize the
      toxicity of long-term steroid use. Pediatr Blood Cancer 2015;62:240-245. (c) 2014
      Wiley Periodicals, Inc.

PMID- 25382691
TI  - The impacts of migraine and anxiety disorders on painful physical symptoms among
      patients with major depressive disorder.
AB  - BACKGROUND: No study has simultaneously investigated the impacts of migraine and
      anxiety disorders on painful physical symptoms (PPS) among patients with major
      depressive disorder (MDD). The study aimed to investigate this issue. METHODS:
      This open-label study enrolled 155 outpatients with MDD, who were then treated
      with venlafaxine 75 mg per day for four weeks. Eighty-five participants with good
      compliance completed the treatment. Migraine was diagnosed according to the
      International Classification of Headache Disorders. MDD and anxiety disorders
      were diagnosed using the Structured Clinical Interview for DSM-IV-TR. The visual
      analog scale (VAS) was used to evaluate the severity of eight PPS. Multiple
      linear and logistic regressions were used to investigate the impacts of migraine
      and anxiety disorders on PPS. RESULTS: Compared with patients without migraine,
      patients with migraine had a greater severity of PPS at baseline and post
      treatment. After controlling for demographic variables and depressive severity,
      migraine independently predicted the intensities of eight PPS at baseline and
      four PPS post-treatment. Moreover, migraine independently predicted poorer
      treatment responses of chest pain and full remission of pains in the head, chest,
      neck and/or shoulder. Anxiety disorders predicted less full remission of pains in
      the abdomen and limbs. CONCLUSION: Migraine and anxiety disorders have negative
      impacts on PPS among patients with MDD. Integrating the treatment of migraine and
      anxiety disorders into the management of depression might help to improve PPS and
      the prognosis of MDD.

PMID- 25382694
TI  - Training intervention study participants to disseminate health messages to the
      community: a new model for translation of clinical research to the community.
AB  - Peer education offers a novel strategy for the translation of health promotion
      interventions in hard-to-reach communities. We describe the development,
      implementation, and evaluation of a program where research participants from a
      cardiovascular risk reduction intervention were invited to be trained as peer
      educators. The goal of the "Heart-to-Heart" intervention was to promote healthy
      behaviors among peers to reduce cardiovascular disease risk. We recruited and
      trained 32 peer educators from a rural, Midwestern community to implement the
      program, and 18 educators reached 175 women and men. A mixed-method analysis
      revealed that those who opted to become peer educators were more likely to be
      African American than participants of the study population from which they were
      recruited. Peer educators reported positive assessments of their encounters with
      respect to preparation and confidence, as well as reinforced personal health
      behaviors. Peer educators' success was evident in reports from the individuals
      they reached, who reported learning new concepts and intention to change
      behavior. Interviews with peer educators revealed their motivations, peer
      education barriers, and recommendations. The Heart-to-Heart model for training
      research participants to serve as peer educators to disseminate behavior change
      messages warrants further investigation as a strategy for the translation of
      research to communities. 

PMID- 25382695
TI  - Mechanisms of ATP release--future therapeutic targets?

PMID- 25382696
TI  - Validity and reproducibility of measures of oropharyngeal dysphagia in preschool
      children with cerebral palsy.
AB  - AIM: The aim of the study was to determine the best measure to discriminate
      between those with oropharyngeal dysphagia (OPD) and those without OPD, among
      young children with cerebral palsy (CP). METHOD: We carried out a cross-sectional
      population-based study involving 130 children with CP aged between 18 months and
      36 months (mean 27.4mo; 81 males, 49 females) classified according to the Gross
      Motor Function Classification Scale (GMFCS) as level I (n=57), II (n=15), III
      (n=23), IV (n=12), or V (n=23). Forty children with CP (mean 28.5mo; 21 males,19
      females, eight for each GMFCS level) were included in the reproducibility sub
      study, and 40 children with typical development (mean 26.2mo; 18 males, 22
      females) were included in the validity sub-study. OPD was assessed using the
      Dysphagia Disorders Survey (DDS), Pre-Speech Assessment Scale (PSAS), and
      Schedule for Oral Motor Assessment (SOMA). We analysed reproducibility using
      inter- and intrarater agreement (percentage) and reliability (kappa values and
      intraclass correlation coefficients). Construct validity was assessed as
      concordance between measures (SOMA, DDS, and PSAS). In the absence of a criterion
      standard measure for OPD, prevalence was estimated using latent class variable
      analysis. Data from the children with typical development were used to propose
      modified OPD cut-points for discriminative validity. RESULTS: All measures had
      strong agreement (>85%) for inter- and intrarater reliability. The SOMA had the
      best specificity (100.0%), but lacked sensitivity (53.0%), whereas the DDS and
      PSAS had high sensitivity (each 100.0%) but lacked specificity (47.1% and 70.6%
      respectively). OPD prevalence when calculated using the web-based estimation was
      65.4%, which was similar to the estimate from the modified cut-points.
      INTERPRETATION: Using the sample of children with typical development and
      modified cut-points, OPD prevalence was lower than estimates with standard
      scoring. We propose using these modified cut-points when administering the DDS,
      PSAS or SOMA in young children with CP.

PMID- 25382697
TI  - Development of the vertebrate tailbud.
AB  - The anatomical tailbud is a defining feature of all embryonic chordates,
      including vertebrates that do not end up with a morphological tail. Due to its
      seamless continuity with trunk tissues, the tailbud is often overlooked as a mere
      extension of the body axis; however, the formation of the tail from the tailbud
      undoubtedly involves unique and distinct mechanisms for forming axial tissues,
      such as the secondary neurulation process that generates the tailbud-derived
      spinal cord. Tailbud formation in the frog Xenopus laevis has been demonstrated
      to involve interaction of three posterior regions of the embryo that first come
      into alignment at the end of gastrulation, and molecular models for tailbud
      outgrowth and patterning have been proposed. While classical studies of other
      vertebrate models, such as the chicken, initially appeared to draw incompatible
      conclusions, molecular studies have subsequently shown the involvement of at
      least some similar genetic pathways. Finally, there is an emerging consensus that
      at least some vertebrate tailbud cells are multipotent progenitors with the
      ability to form tissues normally derived from different germ layers- a trait
      normally associated with regeneration of complex appendages, or stem-like cells.

PMID- 25382698
TI  - Combination of a fillet flap, free tissue transfer, and autologous tissue grafts
      in pelvic reconstruction following retroperitoneal sarcoma: a case report.
AB  - The resection of large pelvic tumors is challenging due to their infiltrative
      nature into multiple structures and organ systems. In this report, we describe
      the use of multiple vascularized and nonvascularized spare parts to reconstruct a
      pelvic defect in a patient with a uniquely large pelvic sarcoma invading the
      spinal canal. A 39-year-old Caucasian female who presented with a large
      retroperitoneal sarcoma where the tumor encased the left ureter, kidney, colon,
      and external iliac vessels and invaded the L3-S1 vertebral bodies. An extensive
      hemipelvectomy and reconstruction was performed over two days. A free thigh and
      leg fillet flap together with ipsilateral fibula flap, based on the superficial
      femoral artery and venae comitantes, was used for spinal reinforcement as well as
      abdominal and pelvic wall reconstruction. The postoperative course was uneventful
      without complications, no flap compromise or wound healing problems. After a
      follow-up period of 4 months, the patient had no complications and returned to
      activities of daily living with mild limitations. The success of this flap
      procedure shows the practicality and usefulness of using the full spectrum of
      tissue transfer for the purposes of a large pelvic reconstruction.

PMID- 25382699
TI  - The Food Web of Boiling Springs Lake Appears Dominated by the Heterolobosean
      Tetramitus thermacidophilus Strain BSL.
AB  - We studied the protist grazers of Boiling Springs Lake (BSL), an acid geothermal
      feature in Lassen Volcanic National Park, using a combination of culture and
      genetic approaches. The major predator in BSL is a vahlkampfiid ameba closely
      related (95% 18S+ITS rRNA identity) to Tetramitus thermacidophilus, a
      heterolobose ameboflagellate recently isolated from volcanic geothermal acidic
      sites in Europe and Russia, as well as an uncultured heterolobosean from the
      nearby Iron Mountain acid mine drainage site. Tetramitus thermacidophilus strain
      BSL is capable of surviving the physical extremes of BSL, with optimal growth at
      38-50  degrees C and pH 2-5. This bacterivore also ingested conidiospores of the
      ascomycete Phialophora sp., but ultrastructural observations reveal the latter
      may not be readily digested, and conidia were not separable from the
      ameoboflagellate culture, suggesting a possible symbiosis. DGGE fingerprint
      transects studies showed the organism is restricted to near-lake environs, and we
      detected an average of ~500 viable cysts/cm(3) sediment on the shoreline. Other
      grazing protists were isolated from lakeshore environments, including the lobose
      amebae Acanthamoeba sp. and Hartmannella sp., and the kinetoplastid flagellate
      Bodo sp., but none could tolerate both low pH and high temperature. These appear
      to be restricted to cooler near lake geothermal features, which also contain
      other potential grazer morphotypes observed but not successfully cultured,
      including ciliates, euglenids, testate amebae, and possible cercozoans. We
      compare the food web of BSL with other acidic or geothermal sites, and discuss
      the impact of protists in this unique environment.

PMID- 25382700
TI  - Efficacy of telavancin, a lipoglycopeptide antibiotic, in experimental models of
      Gram-positive infection.
AB  - Telavancin is a parenteral lipoglycopeptide antibiotic with a dual mechanism of
      action contributing to bactericidal activity against multidrug-resistant Gram
      positive pathogens. It has been approved for the treatment of complicated skin
      and skin structure infections due to susceptible Gram-positive bacteria and
      hospital-acquired/ventilator-associated bacterial pneumonia due to Staphylococcus
      aureus when other alternatives are unsuitable. Telavancin has been demonstrated
      to be efficacious in multiple animal models of soft tissue, cardiac, systemic,
      lung, bone, brain and device-associated infections involving clinically relevant
      Gram-positive pathogens, including methicillin-resistant S. aureus, glycopeptide
      intermediate S. aureus, heterogeneous vancomycin-intermediate S. aureus and
      daptomycin non-susceptible methicillin-resistant S. aureus. The AUC0-24h/MIC
      ratio is the primary pharmacodynamically-linked pharmacokinetic parameter. The
      preclinical data for telavancin supports further investigative clinical
      evaluation of its efficacy in additional serious infections caused by susceptible
      Gram-positive pathogens. 

PMID- 25382702
TI  - Tuning the coordination properties of phenothiazine by regioselective
      introduction of diphenylphosphanyl groups.
AB  - The palladium and platinum complexes of the newly synthesized 1
      (diphenylphosphino)-10-methyl-10H-phenothiazine (1) and the previously reported 3
      (diphenylphosphino)-10-alkyl-10H-phenothiazine [alkyl = Me (2), Et (3)] and 4
      (diphenylphosphino)-10-ethyl-10H-phenothiazine (4) were prepared. Density
      functional calculations were carried out to explain the electronic properties of
      compounds 1, 3 and 4. Compounds 1, 3 and 4 can interact with DNA, as was observed
      in agarose gel electrophoresis experiments. In addition, the cytotoxicity of the
      platinum complexes of ligands 2 and 4 towards breast, colorectal and
      hepatocarcinoma cell lines was studied. 

PMID- 25382701
TI  - Diagnosis and management of acute mastoiditis in a cohort of Italian children.
AB  - OBJECTIVE: The Italian Society for Pediatric Infectious Diseases created a
      registry to determine the management of pediatric acute mastoiditis (AM) in
      Italy. METHODS: A cross-sectional survey of paediatricians was conducted to
      evaluate hospitalization due to AM in Italian pediatric wards between 1 January
      2002, and 31 December 2013. RESULTS: A total of 913 children (561 males, 61.4%)
      were included in this study. The annual number of AM cases significantly
      increased during the study period (30 in 2002 and 98 in 2013) but only among
      older children (>= 4 years old; p = 0.02). AM complications occurred in 69 (7.6%)
      of the children and sequelae were observed in 13 (1.4%) patients. CONCLUSION: The
      annual number of pediatric AM cases admitted to Italian pediatric wards increased
      in the past few years; this increase was strictly age-related. The risk of severe
      AM complications appeared relatively low, and most AM cases could be treated
      conservatively.

PMID- 25382703
TI  - Multiplication of alpha-fetoprotein and protein induced by vitamin K absence-II
      is a powerful predictor of prognosis and recurrence in hepatocellular carcinoma
      patients after a hepatectomy.
AB  - AIM: To evaluate the oncological implications of multiplication of alpha
      fetoprotein (AFP) and protein induced by vitamin K absence or antagonists-II
      (PIVKA-II) in patients with hepatocellular carcinoma (HCC). METHODS: Data were
      prospectively collected from 516 consecutive patients who underwent a curative
      primary hepatectomy for HCC between 1998 and 2010. The AP-factor (AFP * PIVKA-II)
      was evaluated in relation to 2-year survival outcomes by receiver-operator curve
      analysis to determine the cut-off values. Patient survival, recurrence-free
      survival and risk factors were analyzed in accordance with the preoperative AP
      factor. RESULTS: The AP-factor was categorized into three groups depending on the
      serum concentrations of AFP and PIVKA-II as follows: AP1 (n = 206; AFP < 200
      ng/mL and PIVKA-II < 100 mAU/mL), AP2 (n = 152; AFP * PIVKA-II < 10(5) ) and AP3
      (n = 158; AFP * PIVKA-II >= 10(5) ). The AP-factor was found to be significantly
      related to pathological factors such as differentiation, portal vein invasion,
      hepatic vein invasion and intrahepatic metastasis. Multivariate analysis was
      performed to identify the risk factors for survival and recurrence. Albumin, AP
      factor and pathological factors including portal vein invasion, hepatic vein
      invasion and intrahepatic metastasis are independent risk factors for survival.
      Tumor number, AP-factor, and a non-cancerous liver were determinants of
      recurrence. CONCLUSION: The AP-factor is closely related to differentiation and
      microscopic vascular invasion, and was selected by multivariate analysis as an
      independent factor for survival and recurrence, in HCC. Patients hopeful of
      obtaining good outcomes after a hepatectomy could be selected by the AP-factor
      evaluation.

PMID- 25382704
TI  - Felt or false smiles? Volitional regulation of emotional expression in 4-, 6-,
      and 8-year-old children.
AB  - The development of volitional emotion regulation of expression was examined with
      a modified disappointing gift paradigm and strategy for coding children's
      expressions. Forty-nine boys and 49 girls aged 4, 6, and 8 were motivated to
      volitionally deceive an observer by false smiling, regardless of whether they
      received an attractive, unattractive, or no gift. Ten naive observers watched
      children's videotaped behavior in random order and judged the quality of emotion
      and type of gift. This impression analysis indicated that children's competence
      to volitionally regulate their expressions increased with age. In addition, this
      ability was positively associated with children's emotion understanding of how to
      differentiate between emotion and expression. Unexpectedly, girls did not display
      a superior volitional regulation of expression than boys. 

PMID- 25382705
TI  - The combination of irreversible EGFR TKIs and SAHA induces apoptosis and
      autophagy-mediated cell death to overcome acquired resistance in EGFR T790M
      mutated lung cancer.
AB  - To overcome T790M-mediated acquired resistance of lung cancer cells to epidermal
      growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), second generation
      TKIs such as BIBW2992 (afatinib) and third generation TKIs including WZ4002 have
      been developed. However, clinical data on their efficacy in treating T790M mutant
      tumors are lacking. Histone deacetylase (HDAC) inhibitors have been reported to
      arrest cell growth and to lead to differentiation and apoptosis of various cancer
      cells, both in vitro and in vivo. In the present study, we assessed whether the
      combination of suberoylanilide hydroxamic acid (SAHA, vorinostat), a potent HDAC
      inhibitor, and BIBW2992 or WZ4002 could overcome EGFR TKI resistance associated
      with T790M mutation in lung cancer cells. While treatment with BIBW2992 or WZ4002
      alone slightly reduced the viability of PC-9G and H1975 cells, which possess
      T790M mutation, combining them with SAHA resulted in significantly decreased cell
      viability through the activation of the apoptotic pathway. This combination also
      enhanced autophagy occurrence and inhibition of autophagy significantly reduced
      the apoptosis induced by the combination treatment, showing that autophagy is
      required for the enhanced apoptosis. Caspase-independent autophagic cell death
      was also induced by the combination treatment with SAHA and either BIBW2992 or
      WZ4002. Finally, the combined treatment with SAHA and either BIBW2992 or WZ4002
      showed an enhanced anti-tumor effect on xenografts of H1975 cells in vivo. In
      conclusion, the combination of new generation EGFR TKIs and SAHA may be a new
      strategy to overcome the acquired resistance to EGFR TKIs in T790M mutant lung
      cancer. 

PMID- 25382706
TI  - Multifunctional "smart" particles engineered from live immunocytes: toward
      capture and release of cancer cells.
AB  - Multifunctional "smart" particles with magnetic, topographic, cell-targeting, and
      stimulus-responsive properties are obtained using a "live template" strategy.
      These particles exhibit improved efficiency in capture of target cancer cells by
      introducing synergistic topographic interactions, and enable the release of
      captured cells with high viability via reduction of disulfide bonds. Diverse
      multifunctional particles can be designed using the "live template" strategy. 

PMID- 25382708
TI  - Facilitating particularization of repeated similar events with context-specific
      cues.
AB  - Ninety-five dental care patients participated in a quasi-experiment in which they
      were interviewed twice about dental visits they had made during the past ten
      years. Objective truth was established by analysing their dental records. The
      main purpose of the study was to investigate to what extent context-specific cues
      could facilitate particularization (i.e., recollection of events and details) of
      repeated and similar events. A mixed design was employed and the effects of three
      types of cues were explored: two types of context-specific cues vs. cues commonly
      used in police practise when interviewing plaintiffs. In line with our
      hypothesis, context-specific cues tended to be more effective for recollection of
      individual events than the comparison cues. In addition, context-specific cues
      generated more details than the comparison cues and the difference was marginally
      significant. Rehearsal of the memories by telling them to others was associated
      with an increased number of recollected events and details. The results are
      discussed from a legal psychology perspective with focus on recollection of
      repeated abuse. 

PMID- 25382707
TI  - Phytase in non-ruminant animal nutrition: a critical review on phytase activities
      in the gastrointestinal tract and influencing factors.
AB  - This review focuses on phytase functionality in the digestive tract of farmed non
      ruminant animals and the factors influencing in vivo phytase enzyme activity. In
      pigs, feed phytase is mainly active in the stomach and upper part of the small
      intestine, and added phytase activity is not recovered in the ileum. In poultry,
      feed phytase activities are mainly found in the upper part of the digestive
      tract, including the crop, proventriculus and gizzard. For fish with a stomach,
      phytase activities are mainly in the stomach. Many factors can influence the
      efficiency of feed phytase in the gastrointestinal tract, and they can be divided
      into three main groups: (i) phytase related; (ii) dietary related and (iii)
      animal related. Phytase-related factors include type of phytase (e.g. 3- or 6
      phytase; bacterial or fungal phytase origin), the pH optimum and the resistance
      of phytase to endogenous protease. Dietary-related factors are mainly associated
      with dietary phytate content, feed ingredient composition and feed processing,
      and total P, Ca and Na content. Animal-related factors include species, gender
      and age of animals. To eliminate the antinutritional effects of phytate (IP6), it
      needs to be hydrolyzed as quickly as possible by phytase in the upper part of the
      digestive tract. A phytase that works over a wide range of pH values and is
      active in the stomach and upper intestine (along with several other
      characteristics and in addition to being refractory to endogenous enzymes) would
      be ideal.

PMID- 25382709
TI  - Combined antithrombotic therapy of potential value in acute atrial fibrillation
      related stroke.

PMID- 25382711
TI  - High relaxivity Mn(2+)-based MRI contrast agents.
AB  - Stable Mn(2+) mono- and binuclear complexes containing pentadentate 6,6'
      ((methylazanediyl)bis(methylene))dipicolinic acid coordinating units give
      remarkably high relaxivities due to the presence of two inner-sphere water
      molecules. The mononuclear derivative binds human serum albumin (HSA) with an
      association constant of 3372 M(-1), which results in the replacement of the
      coordinated water molecules by donor atoms of protein residues. The dinuclear
      analogue also binds HSA while leaving one of the Mn(2+) centres exposed to the
      solvent with two coordinated water molecules. Thus, this complex shows remarkably
      high relaxivities upon protein binding (39.0 mM(-1)  s(-1) per Mn, at 20 MHz and
      37  degrees C).

PMID- 25382710
TI  - Association of maternal depression and infant nutritional status among women
      living with HIV in Tanzania.
AB  - Antenatal and post-natal depression has demonstrated a significant burden in sub
      Saharan Africa, with rates ranging from 10% to 35%. However, perinatal women
      living with HIV in Tanzania have reported an even greater prevalence of
      depression (43-45%). The primary goal of this study was to examine the
      relationship between maternal depression and infant malnutrition among women
      living with HIV. The design was a retrospective cohort study within the context
      of a randomised controlled trial among women living with HIV and their infants.
      Within this trial, 699 mother-child pairs were analysed for the present study.
      Although antenatal depression was not associated with infant malnutrition and
      post-natal depression was negatively associated [relative risk (RR = 0.80, P =
      0.04], cumulative depression demonstrated a positive association with infant
      wasting (RR = 1.08, P < 0.01) and underweight (RR = 1.03, P < 0.01) after
      controlling for confounding factors. Variation in the association between
      depression and infant nutritional status was observed for episodic vs. chronic
      depression. These findings suggest that providing evidence-based services for
      persistent depression among women living with HIV may have an effect on infant
      malnutrition. In addition, other positive outcomes may be related to infant
      cognitive development as well as HIV disease prognosis and survival among women.

PMID- 25382712
TI  - Erectile dysfunction and premature ejaculation: interrelationships and
      psychosexual factors.
AB  - INTRODUCTION: Both erectile dysfunction (ED) and premature ejaculation (PE)
      impair the quality of sexual intercourse for both men and their female partners.
      AIMS: This study aims to examine with a large representative sample the
      interrelationships of measures of ED, PE, typical intravaginal ejaculatory
      latency time (IELT), men's perceived relationship quality with their mother, and
      age of first being in love. METHODS: In this cross-sectional study, a nationally
      representative sample of 960 Czech coitally experienced men (aged 15-84),
      provided age, International Index of Erectile Function 5-item (IIEF-5), Index of
      Premature Ejaculation (IPE) scores, IELT, rating of relationship with their
      mother, and age at first being in love. MAIN OUTCOME MEASURES: Correlations,
      partial correlations adjusting for age, analysis of covariance (ANCOVA), and
      multiple regression statistical methods were used. RESULTS: IIEF-5, IPE, and IELT
      were significantly intercorrelated (IIEF-5 and IPE: r=0.64). Better IIEF-5 scores
      were associated with younger age at first (and ever) being in love. Poorer IPE
      score, shorter IELT, and mild-moderate ED were associated with poorer perceived
      mother relationship (which was also associated with first being in love at an
      older age). Multiple regression analyses revealed that: (i) greater IELT was
      associated with better erectile function and better mother relationship, but not
      with age; and (ii) IELT of <1 minute was associated with poorer perceived mother
      relationship and poorer IIEF-5, but marginally with age. History of homosexual
      activity was unrelated to IIEF-5, IPE, IELT, and perceived mother relationship
      scores. CONCLUSIONS: The findings suggest that degrees of ED and PE are often
      comorbid, and both ED and PE are associated with less favorable early experiences
      with women. Brody S and Weiss P. Erectile dysfunction and premature ejaculation:
      Interrelationships and psychosexual factors. J Sex Med 2015;12:398-404.

PMID- 25382713
TI  - The work mechanism and sub-bandgap-voltage electroluminescence in inverted
      quantum dot light-emitting diodes.
AB  - Through introducing a probe layer of bis(4,6-difluorophenylpyridinato
      N,C2)picolinatoiridium (FIrpic) between QD emission layer and 4, 4-N, N-
      dicarbazole-biphenyl (CBP) hole transport layer, we successfully demonstrate that
      the electroluminescence (EL) mechanism of the inverted quantum dot light-emitting
      diodes (QD-LEDs) with a ZnO nanoparticle electron injection/transport layer
      should be direct charge-injection from charge transport layers into the QDs.
      Further, the EL from QD-LEDs at sub-bandgap drive voltages is achieved, which is
      in contrast to the general device in which the turn-on voltage is generally equal
      to or greater than its bandgap voltage (the bandgap energy divided by the
      electron charge). This sub-bandgap EL is attributed to the Auger-assisted energy
      up-conversion hole-injection process at the QDs/organic interface. The high
      energy holes induced by Auger-assisted processes can be injected into the QDs at
      sub-bandgap applied voltages. These results are of important significance to
      deeply understand the EL mechanism in QD-LEDs and to further improve device
      performance. 

PMID- 25382715
TI  - Cerebellum and apraxia.
AB  - As early as the beginning of the nineteenth century, a variety of nonmotor
      cognitive and affective impairments associated with cerebellar pathology were
      occasionally documented. A causal link between cerebellar disease and nonmotor
      cognitive and affective disorders has, however, been dismissed for almost two
      centuries. During the past decades, the prevailing view of the cerebellum as a
      mere coordinator of autonomic and somatic motor function has changed
      fundamentally. Substantial progress has been made in elucidating the
      neuroanatomical connections of the cerebellum with the supratentorial association
      cortices that subserve nonmotor cognition and affect. Furthermore, functional
      neuroimaging studies and neurophysiological and neuropsychological research have
      shown that the cerebellum is crucially involved in modulating cognitive and
      affective processes. This paper presents an overview of the clinical and
      neuroradiological evidence supporting the view that the cerebellum plays an
      intrinsic part in purposeful, skilled motor actions. Despite the increasing
      number of studies devoted to a further refinement of the typology and
      anatomoclinical configurations of apraxia related to cerebellar pathology, the
      exact underlying pathophysiological mechanisms of cerebellar involvement remain
      to be elucidated. As genuine planning, organization, and execution disorders of
      skilled motor actions not due to motor, sensory, or general intellectual failure,
      the apraxias following disruption of the cerebrocerebellar network may be
      hypothetically considered to form part of the executive cluster of the cerebellar
      cognitive affective syndrome (CCAS), a highly influential concept defined by
      Schmahmann and Sherman (Brain 121:561-579, 1998) on the basis of four symptom
      clusters grouping related neurocognitive and affective deficits (executive,
      visuospatial, affective, and linguistic impairments). However, since only a
      handful of studies have explored the possible role of the cerebellum in apraxic
      disorders, the pathophysiological mechanisms subserving cerebellar-induced
      apraxia remain to be elucidated. 

PMID- 25382718
TI  - Is floral iridescence a biologically relevant cue in plant-pollinator signalling?
      A response to van der Kooi et al. (2014b).

PMID- 25382719
TI  - Protective mechanisms of acacetin against D-galactosamine and lipopolysaccharide
      induced fulminant hepatic failure in mice.
AB  - This study examined the hepatoprotective effects of acacetin (1), a flavonoid
      isolated from Agastache rugosa, against d-galactosamine (GalN) and
      lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were given an
      intraperitoneal injection of 1 (25, 50, and 100 mg/kg), or the vehicle alone (5%
      dimethyl sulfoxide-saline), 1 h before GalN (800 mg/kg)/LPS (40 MUg/kg) treatment
      and sacrificed at 6 h after GalN/LPS injection. GalN/LPS markedly increased
      mortality and serum aminotransferase activity, and these increases were
      attenuated by 1. GalN/LPS increased serum tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6) levels, while 1 attenuated TNF-alpha levels and further
      increased IL-6 levels. GalN/LPS increased protein expression of toll-like
      receptor 4, phosphorylation of extracellular signal-related kinase, and p38 and c
      Jun N-terminal kinase and increased nuclear protein expression of nuclear factor
      kappaB; these increases were attenuated by 1. GalN/LPS increased Atg5 and Atg7
      protein expressions, and these increases were augmented by 1. GalN/LPS activated
      autophagic flux as indicated by decreased microtubule-associated protein 1 light
      chain 3-II and sequestosome1/p62 protein expression. This activation was enhanced
      by 1. These findings suggest that 1 protects against GalN/LPS-induced liver
      injury by suppressing TLR4 signaling and enhancing autophagic flux. 

PMID- 25382720
TI  - Gas bubble dynamics in soft materials.
AB  - Epstein and Plesset's seminal work on the rate of gas bubble dissolution and
      growth in a simple liquid is generalized to render it applicable to a gas bubble
      embedded in a soft elastic solid. Both the underlying diffusion equation and the
      expression for the gas bubble pressure were modified to allow for the non-zero
      shear modulus of the medium. The extension of the diffusion equation results in a
      trivial shift (by an additive constant) in the value of the diffusion
      coefficient, and does not change the form of the rate equations. But the use of a
      generalized Young-Laplace equation for the bubble pressure resulted in
      significant differences on the dynamics of bubble dissolution and growth,
      relative to an inviscid liquid medium. Depending on whether the salient
      parameters (solute concentration, initial bubble radius, surface tension, and
      shear modulus) lead to bubble growth or dissolution, the effect of allowing for a
      non-zero shear modulus in the generalized Young-Laplace equation is to speed up
      the rate of bubble growth, or to reduce the rate of bubble dissolution,
      respectively. The relation to previous work on visco-elastic materials is
      discussed, as is the connection of this work to the problem of Decompression
      Sickness (specifically, "the bends"). Examples of tissues to which our
      expressions can be applied are provided. Also, a new phenomenon is predicted
      whereby, for some parameter values, a bubble can be metastable and persist for
      long times, or it may grow, when embedded in a homogeneous under-saturated soft
      elastic medium. 

PMID- 25382714
TI  - Consensus paper: radiological biomarkers of cerebellar diseases.
AB  - Hereditary and sporadic cerebellar ataxias represent a vast and still growing
      group of diseases whose diagnosis and differentiation cannot only rely on
      clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear
      medicine techniques allows for characterization of structural and functional
      abnormalities underlying symptomatic ataxias. These methods thus constitute a
      potential source of radiological biomarkers, which could be used to identify
      these diseases and differentiate subgroups of them, and to assess their severity
      and their evolution. Such biomarkers mainly comprise qualitative and quantitative
      data obtained from MR including proton spectroscopy, diffusion imaging,
      tractography, voxel-based morphometry, functional imaging during task execution
      or in a resting state, and from SPETC and PET with several radiotracers. In the
      current article, we aim to illustrate briefly some applications of these
      neuroimaging tools to evaluation of cerebellar disorders such as inherited
      cerebellar ataxia, fetal developmental malformations, and immune-mediated
      cerebellar diseases and of neurodegenerative or early-developing diseases, such
      as dementia and autism in which cerebellar involvement is an emerging feature.
      Although these radiological biomarkers appear promising and helpful to better
      understand ataxia-related anatomical and physiological impairments, to date, very
      few of them have turned out to be specific for a given ataxia with atrophy of the
      cerebellar system being the main and the most usual alteration being observed.
      Consequently, much remains to be done to establish sensitivity, specificity, and
      reproducibility of available MR and nuclear medicine features as diagnostic,
      progression and surrogate biomarkers in clinical routine. 

PMID- 25382721
TI  - Post-extraction evaluation of sockets with one plate loss--a microtomographic and
      histological study.
AB  - AIM: The aim of this study is to evaluate the characteristics of socket repair
      after teeth extraction with loss of a bone plate. MATERIAL AND METHOD: Lower
      incisors were extracted from 120-day-old male rabbits. A standardized defect of 5
      mm in the buccal plate was created in one of the socket sites. Furthermore,
      complete closures of the sockets entrance were performed. Two groups of biopsies
      were obtained: one with 14 days of healing and the other with 112, to perform the
      micro-CT and histological evaluations of the tested group with plate loss
      comparing with the control group with the intact buccal bone wall. RESULTS: Plate
      loss sites demonstrated reduction in width when compared to the intact ones and,
      this difference decreased with time. CONCLUSION: Long-term analysis showed that
      plate loss interfered in final ridge measurements by reducing the middle portion
      of the socket width compared to the intact plate sockets. The histological and
      micro-CT qualitative analysis showed that both sites presented similar pattern of
      healing, despite the reduced dimension found in plate loss sites.

PMID- 25382722
TI  - A new turn-on chemosensor for bio-thiols based on the nanoaggregates of a
      tetraphenylethene-coumarin fluorophore.
AB  - In this work, a tetraphenylethene-coumarin hybrid fluorophore (TPE-Cou) that
      contains a Schiff base form is designed and synthesized. A combination of
      plentiful optical properties and chemical reactivity towards thiols allows TPE
      Cou to work as an excellent turn-on probe of thiols with a wide linear range,
      revealing the great potential of this dye as a quantitative fluorescence
      indicator. By means of NMR and optical spectrum analyses, a mechanistic picture
      at the molecular level has been drawn to illustrate how this dye works as a bio
      thiol-sensitive fluorescent probe. 

PMID- 25382723
TI  - Tributyltin alters secretion of interleukin 1 beta from human immune cells.
AB  - Tributyltin (TBT) has been used as a biocide in industrial applications such as
      wood preservation, antifouling paint and antifungal agents. Owing to its many
      uses, it contaminates the environment and has been found in human blood samples.
      Interleukin-1 beta (IL-1beta) is a pro-inflammatory cytokine that promotes cell
      growth, tissue repair and immune response regulation. Produced predominately by
      both monocytes and macrophages, IL-1beta appears to increase the invasiveness of
      certain tumors. This study shows that TBT modifies the secretion of IL-1beta from
      increasingly reconstituted preparations of human immune cells. IL-1beta secretion
      was examined after 24-, 48-h or 6-day exposures to TBT in highly enriched human
      natural killer (NK) cells, monocyte-depleted peripheral blood mononuclear cells
      (MD-PBMCs), PBMCs, granulocytes and a preparation combining both PBMCs and
      granulocytes (PBMCs+granulocytes). TBT altered IL-1beta secretion from all of the
      cell preparations. The 200 nM concentration of TBT normally blocked the secretion
      of IL-1beta, whereas lower concentrations (usually 5-50 nM) elevated secretion of
      IL-1beta. Examination of the signaling pathway(s) responsible for the elevated
      secretion of IL-1beta was carried out in MD-PBMCs. Pathways examined were IL
      1beta processing (Caspase-1), mitogen-activated protein kinases (MAPKs) and
      nuclear factor kappa B (NFkappaB). Results indicated that MAPK pathways (p44/42
      and p38) appear to be the targets of TBT that lead to increased IL-1beta
      secretion from immune cells. These results from human immune cells show IL-1beta
      dysregulation by TBT is occurring ex vivo. Thus, the potential for in vivo
      effects on pro-inflammatory cytokine levels may possibly be a consequence of TBT
      exposures.

PMID- 25382724
TI  - 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside protects human umbilical vein
      endothelial cells against lysophosphatidylcholine-induced apoptosis by
      upregulating superoxide dismutase and glutathione peroxidase.
AB  - 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-d-glucoside (TSG) has been shown to
      protect human umbilical vein endothelial cells (HUVECs) from
      lysophosphatidylcholine (LPC)-induced injury; however, the underlying molecular
      mechanism remains to be determined. The aim of this study was to investigate the
      protective mechanism of TSG against LPC-induced injury in HUVECs. We established
      a stable LPC-induced cell model by treating HUVECs with various concentrations of
      LPC and found 10.0 ug/mL of LPC to be optimal for inducing HUVECs injury. The
      effects of TSG on LPC-induced cell injury were assessed by cell counting kit-8,
      apoptosis assay, transmission electron microscope, and measurement of
      malondialdehyde (MDA), the antioxidant enzymes superoxide dismutase (SOD),
      reactive oxygen species (ROS), glutathione peroxidase, and mitochondrial membrane
      potential. The mRNA and protein levels of caspase-3, Bax, Bcl-2, PARP-1, and
      cytochrome C were assayed by real-time reverse transcriptase-polymerase chain
      reaction and immunoblotting, respectively. TSG pretreatment was able to prevent
      LPC-induced HUVECs injury and restore cell viability in a concentration-dependent
      manner. LPC treated cells showed typical apoptotic morphological changes
      including cytoplasmic vacuolation, swollen mitochondria, and characteristic
      biochemical hallmarks of apoptosis including loss of mitochondrial membrane
      potential, activation of caspase-3, decrease of Bcl-2, increase of PARP-1,
      upregulation of Bax, and release of cytochrome C, all of which were apparently
      inhibited by TSG pretreatment. Treatment of HUVECs with LPC led to decrease of
      SOD and glutathione peroxidase in addition to rapid increase of MDA and ROS
      levels. Pretreatment with TSG restored SOD and glutathione peroxidase levels to
      that of normal levels, and significantly decreased ROS and MDA levels. Our data
      indicate that TSG inhibits apoptosis of HUVECs mediated by LPC through blocking
      the mitochondrial apoptotic pathway and suggest that the mechanisms underlying
      the protective effects of TSG are related to the activation of SOD and
      glutathione peroxidase, the clearance of intracellular ROS, and reduction of
      lipid peroxidation.

PMID- 25382725
TI  - Teat Morphology Characterization With 3D Imaging.
AB  - The objective of this study was to visualize, in a novel way, the morphological
      characteristics of bovine teats to gain a better understanding of the detailed
      teat morphology. We applied silicone casting and 3D digital imaging in order to
      obtain a more detailed image of the teat structures than that seen in previous
      studies. Teat samples from 65 dairy cows over 12 months of age were obtained from
      cows slaughtered at an abattoir. The teats were classified according to the teat
      condition scoring used in Finland and the lengths of the teat canals were
      measured. Silicone molds were made from the external teat surface surrounding the
      teat orifice and from the internal surface of the teat consisting of the
      papillary duct, Furstenberg's rosette, and distal part of the teat cistern. The
      external and internal surface molds of 35 cows were scanned with a 3D laser
      scanner. The molds and the digital 3D models were used to evaluate internal and
      external teat surface morphology. A number of measurements were taken from the
      silicone molds. The 3D models reproduced the morphology of the teats accurately
      with high repeatability. Breed didn't correlate with the teat classification
      score. The rosette was found to have significant variation in its size and number
      of mucosal folds. The internal surface morphology of the rosette did not
      correlate with the external surface morphology of the teat implying that it is
      relatively independent of milking parameters that may impact the teat canal and
      the external surface of the teat.

PMID- 25382727
TI  - Making the case for a more accurate cardiovascular disease risk assessment tool
      for Indigenous Australians.
AB  -  

PMID- 25382726
TI  - High-grade encapsulated papillary carcinoma of the breast: an under-recognized
      entity.
AB  - AIMS: Encapsulated papillary carcinoma (EPC) is a recognized special type of
      breast carcinoma. Despite compelling evidence indicating its invasive nature,
      although not of a conventional form, the current consensus is to manage EPC as an
      in-situ disease, based on its indolent clinical behaviour. Although most EPCs are
      recognized to be of low and intermediate grade, a distinct proportion of these
      tumours do show high cytonuclear grade features. The existence and behaviour of
      these rare high-grade variants remains to be defined. We aim to characterise
      these tumours and provide evidence to guide their management. METHODS AND
      RESULTS: In this study, we have identified 12 high-grade EPCs without associated
      conventional stromal invasion. To further characterize these high-grade tumours,
      a series of invasive papillary carcinomas (n = 30) were assessed for the
      coexistence of EPC. The literature was also reviewed. Approximately 3% of pure
      EPCs showed high-grade features as defined by nuclear pleomorphism and increased
      mitotic activity. These tumours not only showed histological features associated
      with aggressive behaviour, but were also often hormone receptor-negative, tended
      to be of larger size, and were more frequently associated with stromal invasion.
      Of the 10 patients with follow-up data, one with pure high-grade EPC developed
      recurrence and died of her disease. CONCLUSION: High-grade EPC is rare, and its
      histological features and more aggressive clinical behaviour suggest that
      consideration should be given to managing it in a similar fashion to conventional
      forms of invasive breast carcinoma, based on established clinicopathological
      parameters.

PMID- 25382728
TI  - Plasma modification of poly(2-heptadecyl-4-vinylthieno[3,4-d]thiazole) low
      bandgap polymer and its application in solar cells.
AB  - For the first time, we here propose a green methodology to modify a low bandgap
      polymer for highly efficient solar cells using atmospheric pressure plasma jet or
      soft plasma operating on different feeding gases (air, Ar and N2). The physical
      properties of the modified polymer were investigated using conductivity
      measurements, UV-visible spectroscopy, photoluminescence spectroscopy, X-ray
      photoelectron spectroscopy, cyclic voltammograms, atomic force microscopy,
      cathodoluminescence and confocal Raman spectroscopy. Further, we examined the
      variation of the work function of the polymer before and after plasma treatment
      using a gamma-focused ion beam. Additionally, photovoltaic cells based on the
      plasma-modified polymer having ITO/PEDOT:PSS/PHVTT (with or without plasma
      modification):PC71BM/LiF/Al configuration were fabricated and then characterized.
      We found that the power conversion efficiency (PCE) of the plasma-modified
      polymer increased dramatically as compared to the control polymer (without plasma
      treatment). PCE of the control polymer was found to be 4.11%, while after air, Ar
      and N2 gas plasma treatment the polymer showed PCEs of 4.85%, 4.87% and 5.14%
      respectively. Thus, plasma treatment not only alters the surface properties, but
      also modifies the bulk properties (changes in HOMO and LUMO bandgap level).
      Hence, this work provides new dimensions to explore more about plasma and polymer
      chemistry. 

PMID- 25382729
TI  - Monocyte chemoattractant protein 1 (MCP-1/CCL2) contributes to thymus atrophy in
      acute myeloid leukemia.
AB  - Recent studies on acute myelogenous leukemia (AML) patients have revealed the
      existence of T-cell immunodeficiencies, characterized by peripheral T lymphocytes
      that are unable to interact with blasts, reduced thymic emigrants and oligoclonal
      restricted repertoires. These observations suggest that there is a profound
      thymic dysregulation, which is difficult to study in AML patients. Using the
      C1498 AML mouse model, we demonstrated that leukemia development was associated
      with thymus atrophy, which was defined by abnormal organ weight and reduced
      cellularity. In addition, we observed a dramatic loss of peripheral CD4(+) and
      CD8(+) T-cell numbers with increased frequencies of CD4(+) FoxP3(+) regulatory
      and activated/memory T cells. Investigating the mechanisms leading to this
      atrophy, we observed a significant accumulation of the monocyte chemoattractant
      protein 1 (MCP-1/CCL2) in thymi of leukemic mice. Treatment of AML-bearing
      animals with a blocking anti-CCL2 antibody revealed a lower tumor burden,
      augmented antileukemic T-cell responses, and improved survival rate compared to
      nontreated mice. These results were not observed when neutralization of CCL2 was
      performed in thymectomized mice. Altogether, we show that the CCL2 protein
      participates in thymic atrophy in AML mice, and this could have important
      implications for future immunotherapeutic strategies. 

PMID- 25382730
TI  - Nationwide epidemiological survey of 169 patients with adult Still's disease in
      Japan.
AB  - OBJECTIVES: A nationwide survey was conducted to assess the number of patients,
      clinical aspects, treatment, and prognosis of adult Still's disease (ASD) in
      Japan. METHODS: A primary questionnaire was sent to randomly selected medical
      institutions in order to estimate the number of patients. We sent a secondary
      questionnaire to the same institutions to characterize the clinical
      manifestations and treatment of ASD. RESULTS: The estimated prevalence of ASD was
      3.9 per 100,000. Analysis of 169 patients showed a mean age at onset of 46 years.
      The main clinical symptoms were fever, arthritis, and typical rash in agreement
      with previous surveys. Oral glucocorticoids were used to treat 96% of the
      patients, while methotrexate was used in 41% and biological agents were used in
      16%. Lymphadenopathy and macrophage activation syndrome were significantly
      associated with increased risk of relapse (P < 0.05, each). Patients who achieved
      remission after tocilizumab therapy had significantly longer disease duration
      (6.2 years) than patients who did not (1.9 years) (p < 0.05). CONCLUSIONS: The
      2010-2011 nationwide survey of ASD identified important changes in treatment and
      improvement of prognosis compared with previous surveys.

PMID- 25382731
TI  - Risk factors for systemic inflammatory response after congenital cardiac surgery.
AB  - BACKGROUND: This study aims to assess the frequency of systemic inflammatory
      response syndrome (SIRS) following congenital heart surgery and risk factors
      associated with this clinical syndrome. METHODS: Charts of all patients
      undergoing surgery for congenital heart disease in a single institution over a
      five-year period were analyzed retrospectively. The presence of SIRS was
      evaluated based on the criteria of the International Pediatric Sepsis Consensus
      Conference. RESULTS: Of the 246 patients included in the study 22 (8.9%) had
      clinical parameters indicating SIRS. The patients in the SIRS group had
      significantly longer cardiopulmonary bypass time (105.14 +/- 27.27 vs. 66.86 +/-
      26.64 min; p < 0.01), aortic cross clamp time (69.36 +/- 21.52 vs. 44.30 +/-
      24.27 min; p < 0.01), higher postoperative alanine aminotransferase (1419.00 +/-
      3260.99 vs. 81.95 +/- 808.61 U/L; p < 0.01) and aspartate aminotransferase
      (2137.14 +/- 4905.40 vs. 171.33 +/- 1303.21 U/L; p < 0.01), white blood cell
      counts (20,827 +/- 3603 vs. 12,242 +/- 3782/uL; p < 0.01) and lower body surface
      area (0.52 +/- 0.32 vs. 0.71 +/- 0.36 m(2) ; p < 0.05) compared to patients in
      the no-SIRS group. Binary logistic regression revealed cardiopulmonary bypass
      time (OR: 1.05, p < 0.05), low body weight (<10 kg) (OR: 2.44; p < 0.05), and
      preoperative diagnosis of right to left shunt congenital heart disease (OR: 8.06;
      p < 0.01) as independent predictors of SIRS. SIRS was also found to be a strong
      independent predictor of mortality (OR: 10.13, p < 0.01). CONCLUSIONS: SIRS after
      congenital heart surgery is associated with increased mortality. Independent risk
      factors for SIRS in the patient population of the study were cardiopulmonary
      bypass time, body weight below 10 kg and preoperative diagnosis of right to left
      shunt congenital heart disease.

PMID- 25382733
TI  - Thermochromism in yttrium iron garnet compounds.
AB  - Polycrystalline yttrium iron garnet (Y3Fe5O12, hereafter labeled YIG) has been
      synthesized by solid-state reaction, characterized by X-ray diffraction,
      Mossbauer spectroscopy, and UV-vis-NIR diffuse reflectance spectroscopy, and its
      optical properties from room temperature (RT) to 300  degrees C are discussed.
      Namely, its greenish color at RT is assigned to an O(2-) -> Fe(3+) ligand-to
      metal charge transfer at 2.57 eV coupled with d-d transitions peaking at 1.35 and
      2.04 eV. When the temperature is raised, YIG displays a marked thermochromic
      effect; i.e., the color changes continuously from greenish to brownish, which
      offers opportunities for potential application as a temperature indicator for
      everyday uses. The origin of the observed thermochromism is assigned to a gradual
      red shift of the ligand-to-metal charge transfer with temperature while the
      positioning in energy of the d-d transitions is almost unaltered. Attempts to
      achieve more saturated colors via doping (e.g., Al(3+), Ga(3+), Mn(3+), ...)
      remained unsuccessful except for chromium. Indeed, Y3Fe5O12:Cr samples exhibit at
      RT the same color than the undoped garnet at 200  degrees C. The introduction of
      Cr(3+) ions strongly impacts the color of the Y3Fe5O12 parent either by an
      inductive effect or, more probably, by a direct effect on the electronic
      structure of the undoped material with formation of a midgap state. 

PMID- 25382732
TI  - Cancer stem cell division: when the rules of asymmetry are broken.
AB  - Asymmetric division of stem cells is a highly conserved and tightly regulated
      process by which a single stem cell produces two daughter cells and
      simultaneously directs the differential fate of both: one retains its stem cell
      identity while the other becomes specialized and loses stem cell properties.
      Coordinating these events requires control over numerous intra- and extracellular
      biological processes and signaling networks. In the initial stages, critical
      events include the compartmentalization of fate determining proteins within the
      mother cell and their subsequent passage to the appropriate daughter cell.
      Disturbance of these events results in an altered dynamic of self-renewing and
      differentiation within the cell population, which is highly relevant to the
      growth and progression of cancer. Other critical events include proper asymmetric
      spindle assembly, extrinsic regulation through micro-environmental cues, and
      noncanonical signaling networks that impact cell division and fate determination.
      In this review, we discuss mechanisms that maintain the delicate balance of
      asymmetric cell division in normal tissues and describe the current understanding
      how some of these mechanisms are deregulated in cancer. The universe is
      asymmetric and I am persuaded that life, as it is known to us, is a direct result
      of the asymmetry of the universe or of its indirect consequences. The universe is
      asymmetric. -Louis Pasteur. 

PMID- 25382734
TI  - Low sodium and high potassium intake for cardiovascular prevention: evidence
      revisited with emphasis on challenges in sub-Saharan Africa.
AB  - Reduction in dietary salt intake and increase in potassium intake can make a
      major contribution to the prevention and control of hypertension and
      consequential cardiovascular disease, especially in sub-Saharan Africa (SSA)
      where prevalence rates are highest. African populations are going through a
      westernization of their traditional eating patterns, with a shift towards a
      US/Western-style diet, which contains an excessive amount of salt. Currently, the
      mean sodium intake in SSA populations is far above the recommended daily
      allowance. Besides, potassium intake is low, and, particularly, the supply of
      fruits and vegetables that are important sources of potassium is insufficient to
      meet current and growing population needs in SSA countries. Context-relevant
      strategies are needed for population-wide sodium intake reduction and increase in
      potassium intake. 

PMID- 25382735
TI  - Visualization of latent blood stains using visible reflectance hyperspectral
      imaging and chemometrics.
AB  - The detection of latent traces is an important aspect of crime scene
      investigation. Blood stains on black backgrounds can be visualized using
      chemiluminescence, which is invasive and requires a darkened room, or near
      infrared photography, for which investigators need to change filters manually to
      optimize contrast. We demonstrated the performance of visible reflectance
      hyperspectral imaging (400-720 nm) for this purpose. Several processing methods
      were evaluated: single wavelength bands, ratio images, principal component
      analysis (PCA), and "SIMPLe-to-use Interactive Self-modeling Mixture Analysis"
      (SIMPLISMA). Using these methods, we were able to enhance the contrast between
      blood stains and 12 different fabrics. On black cotton, blood dilutions were
      visible with a minimal concentration of 25% of whole blood. The hyperspectral
      camera system used in this study is portable and wireless, which makes it
      suitable for crime scene use. The described technique is noncontact and
      nondestructive, so all traces are preserved for further analysis.

PMID- 25382736
TI  - Chiral metal-organic frameworks bearing free carboxylic acids for organocatalyst
      encapsulation.
AB  - Two chiral carboxylic acid functionalized micro- and mesoporous metal-organic
      frameworks (MOFs) are constructed by the stepwise assembly of triple-stranded
      heptametallic helicates with six carboxylic acid groups. The mesoporous MOF with
      permanent porosity functions as a host for encapsulation of an enantiopure
      organic amine catalyst by combining carboxylic acids and chiral amines in situ
      through acid-base interactions. The organocatalyst-loaded framework is shown to
      be an efficient and recyclable heterogeneous catalyst for the asymmetric direct
      aldol reactions with significantly enhanced stereoselectivity in relative to the
      homogeneous organocatalyst. 

PMID- 25382737
TI  - The impact of timing and duration of thiopurine treatment on colectomy in
      ulcerative colitis: a national population-based study of incident cases between
      1989-2009.
AB  - BACKGROUND: The role of thiopurines in altering the risk of colectomy in
      ulcerative colitis (UC) remains unclear. AIMS: To examine predictors of colectomy
      in UC and determine the impact of thiopurines on the risk of colectomy. METHODS:
      We constructed a population-based cohort of incident cases of UC in the United
      Kingdom between 1989 and 2009. We determined trends in thiopurine usage and
      colectomy for three defined cohorts: era 1 (1989-1995), era 2 (1996-2002), era 3
      (2003-2009). We used Cox regression to determine predictors of colectomy and
      quantified the impact of duration and timing of thiopurine use on the risk of
      colectomy. RESULTS: We identified 8673 incident cases of UC. 5-year colectomy
      rates increased from 4.2%, 5.1% to 6.9% (P = 0.001) for era 1, era 2 and era 3,
      respectively, despite increasing thiopurine use. This was not significant after
      adjustment for predictors of colectomy (P = 0.06). There was a higher risk of
      colectomy in men (HR 1.44, 95% CI: 1.19-1.73), those diagnosed at an early age
      (HR 1.35, 95% CI: 1.04-1.75; 16-24 vs. 25-64) and early steroid users (HR 1.94,
      95% CI: 1.59-2.37). 5-ASA users were less likely to require a colectomy (HR 0.35,
      95% CI: 0.28-0.44). Amongst thiopurine users, those treated for greater than 12
      months had a 71% reduction in risk of colectomy (HR 0.29, 95% CI: 0.21-0.40).
      Early thiopurines offered no additional benefit. CONCLUSIONS: Thiopurine exposure
      for greater than 12 months reduces the likelihood of colectomy by 71%. Young men
      and those requiring steroids within 3 months of diagnosis are at greatest risk of
      colectomy, and most likely to benefit from sustained thiopurine use.

PMID- 25382738
TI  - Chronic physical activity limits blood rheology alterations in transgenic SAD
      mice.

PMID- 25382739
TI  - Chlamydia trachomatis protein CT009 is a structural and functional homolog to the
      key morphogenesis component RodZ and interacts with division septal plane
      localized MreB.
AB  - Cell division in Chlamydiae is poorly understood as apparent homologs to most
      conserved bacterial cell division proteins are lacking and presence of elongation
      (rod shape) associated proteins indicate non-canonical mechanisms may be
      employed. The rod-shape determining protein MreB has been proposed as playing a
      unique role in chlamydial cell division. In other organisms, MreB is part of an
      elongation complex that requires RodZ for proper function. A recent study
      reported that the protein encoded by ORF CT009 interacts with MreB despite low
      sequence similarity to RodZ. The studies herein expand on those observations
      through protein structure, mutagenesis and cellular localization analyses.
      Structural analysis indicated that CT009 shares high level of structural
      similarity to RodZ, revealing the conserved orientation of two residues critical
      for MreB interaction. Substitutions eliminated MreB protein interaction and
      partial complementation provided by CT009 in RodZ deficient Escherichia coli.
      Cellular localization analysis of CT009 showed uniform membrane staining in
      Chlamydia. This was in contrast to the localization of MreB, which was restricted
      to predicted septal planes. MreB localization to septal planes provides direct
      experimental observation for the role of MreB in cell division and supports the
      hypothesis that it serves as a functional replacement for FtsZ in Chlamydia. 

PMID- 25382740
TI  - Effects of 60-day bed rest with and without exercise on cellular and humoral
      immunological parameters.
AB  - Exercise at regular intervals is assumed to have a positive effect on immune
      functions. Conversely, after spaceflight and under simulated weightlessness
      (e.g., bed rest), immune functions can be suppressed. We aimed to assess the
      effects of simulated weightlessness (Second Berlin BedRest Study; BBR2-2) on
      immunological parameters and to investigate the effect of exercise (resistive
      exercise with and without vibration) on these changes. Twenty-four physically and
      mentally healthy male volunteers (20-45 years) performed resistive vibration
      exercise (n=7), resistance exercise without vibration (n=8) or no exercise (n=9)
      within 60 days of bed rest. Blood samples were taken 2 days before bed rest, on
      days 19 and 60 of bed rest. Composition of immune cells was analyzed by flow
      cytometry. Cytokines and neuroendocrine parameters were analyzed by Luminex
      technology and ELISA/RIA in plasma. General changes over time were identified by
      paired t-test, and exercise-dependent effects by pairwise repeated measurements
      (analysis of variance (ANOVA)). With all subjects pooled, the number of
      granulocytes, natural killer T cells, hematopoietic stem cells and CD45RA and
      CD25 co-expressing T cells increased and the number of monocytes decreased
      significantly during the study; the concentration of eotaxin decreased
      significantly. Different impacts of exercise were seen for lymphocytes, B cells,
      especially the IgD(+) subpopulation of B cells and the concentrations of IP-10,
      RANTES and DHEA-S. We conclude that prolonged bed rest significantly impacts
      immune cell populations and cytokine concentrations. Exercise was able to
      specifically influence different immunological parameters. In summary, our data
      fit the hypothesis of immunoprotection by exercise and may point toward even
      superior effects by resistive vibration exercise.

PMID- 25382741
TI  - Breast cancer arising within fibroadenoma: collective analysis of case reports in
      the literature and hints on treatment policy.
AB  - BACKGROUND: Breast cancer arising within a fibroadenoma (BcaFad) is rare; the
      rate varies from 0.002% to 0.125% in fibroadenoma specimens. Owing to its rarity,
      the clinicopathologic feature and treatment principle of BcaFad is still not
      clear. Therefore, the aim of this study was to perform a collective analysis of
      case reports in the literature to identify the characteristics and optimal
      treatment for BcaFad. METHODS: We analyzed an aggregated sample of 30 patients
      with BcaFad from case reports in the literature (n=24 cases) and our present
      study (n=6 cases). We collected and analyzed the clinicopathologic features and
      prognoses of patients with BcaFad, as well as treatments they received. RESULTS:
      The patients' mean age at diagnosis was 46.9 years. Twenty BcaFad patients
      (66.7%) received breast-conserving surgery (BCS), and nine other patients (30.0%)
      were treated with mastectomy. The rate of lymph node metastasis in BcaFad
      patients was 23.8%. The breakdown of the histological types of BcaFad was
      invasive ductal carcinoma (53.3%), followed by ductal carcinoma in situ (23.3%),
      lobular carcinoma in situ (16.7%) and invasive lobular carcinoma (13.3%). More
      than half of patients with positive hormone receptor status received hormone
      therapy. Most BcaFad patients with lymph node metastases received chemotherapy,
      and 20.0% of BcaFad patients treated with BCS received further radiotherapy. Only
      one patient had recurrence after surgery, and another had lung metastasis when
      diagnosed with BcaFad. CONCLUSIONS: Most BcaFad patients could be managed by BCS.
      Adjuvant radiotherapy could be performed, but was not mandatory. Chemotherapy
      should be considered as a treatment option in the presence of lymph node
      metastasis.

PMID- 25382742
TI  - Comparison of pain outcomes between two anti-GD2 antibodies in patients with
      neuroblastoma.
AB  - BACKGROUND: Addition of anti-GD2 antibody ch14.18 to the treatment of
      neuroblastoma has improved outcomes. The most common side effect of ch14.18 is
      neuropathic pain, which may in part be complement-mediated. Hu14.18K322A is a
      humanized anti-GD2 antibody designed to diminish complement activation and induce
      less pain. We compare the pain outcomes in patients treated with ch14.18 and
      those treated with hu14.18K322A, and explore dose-dependent relationships between
      pain scores, opioid requirements, and complement levels in patients treated with
      hu14.18K322A. PROCEDURE: Opioid (morphine equivalent mg/kg) and anxiolytic
      requirements during course 1 (4 days) in patients treated with hu14.18K322A and
      ch14.18 were reviewed. Correlations between antibody dose and pain scores, opioid
      requirements, and complement levels were examined for patients receiving
      hu14.18K322A. RESULTS: Patients treated with hu14.18K322A (n = 19) had lower
      opioid requirements than those who received ch14.18 (n = 9). The differences in
      median opioid requirements (mg/kg) were statistically significant for the overall
      course (1.57 vs. 2.41, P = 0.019) as well as for Days 3 (0.34 vs. 0.65, P =
      0.005), and 4 (0.32 vs. 0.64, P = 0.010). No difference in anxiolytic use was
      observed between the two groups. In the group treated with hu14.18K322A, we found
      a positive correlation between antibody dose administered and pain scores, but no
      correlation between antibody dose and opioid requirements or changes in
      complement levels. CONCLUSIONS: In this retrospective analysis, hu14.18K322A
      induced less pain than ch14.18 based on opioid requirements. Pediatr Blood Cancer
      2015;62:224-228. (c) 2014 Wiley Periodicals, Inc.

PMID- 25382744
TI  - Cerebral oxygenation is associated with neurodevelopmental outcome of preterm
      children at age 2 to 3 years.
AB  - AIM: The aim of the study was to determine whether regional cerebral tissue
      oxygen saturation (r(c)SO2) and fractional tissue oxygen extraction (FTOE), using
      near-infrared spectroscopy, are associated with neurodevelopmental outcome of
      preterm infants. METHOD: We measured rc SO2 on days 1, 2, 3, 4, 5, 8, and 15
      after birth in 83 preterm infants (<32wks gestational age), and calculated
      FTOE=(SpO2 -r(c)SO2)/SpO2. Cognitive, motor, neurological, and behavioural
      outcomes were determined at 2 to 3 years using the Bayley Scales of Infant and
      Toddler Development, Third Edition (BSID-III), an age-specific neurological
      examination, and the Child Behavior Checklist (CBCL) respectively. Multiple
      linear regression analyses were used to determine whether r(c)SO2 and FTOE
      contributed to outcome. RESULTS: We followed up 67 infants. The lower quartile
      (P(25-50)) and highest quartile (P(75-100)) of r(c)SO2 on day 1 were associated
      with poorer cognitive outcome (p=0.044 and p=0.008 respectively). A lower area
      under the curve (AUC; over 15d) of r(c)SO2 was associated with poorer cognitive
      outcome (p=0.014). The lower quartile (P(25-50)) AUC of r(c)SO2 was associated
      with poorer fine motor outcome (p=0.004). The amount of time r(c)SO2 <50% on day
      1 was negatively associated with gross motor outcome (p=0.002). The highest
      quartile of FTOE on day 1 was associated with poorer total motor outcome
      (p=0.041). INTERPRETATION: Cerebral oxygen saturation during the first 2 weeks
      after birth is associated with neurodevelopmental outcome of preterm infants at 2
      to 3 years. High and low r(c)SO2 on day 1 were associated with poorer
      neurodevelopmental outcome.

PMID- 25382743
TI  - Patterns of surveillance imaging after nephrectomy in the Medicare population.
AB  - OBJECTIVES: To characterize patterns of imaging surveillance after nephrectomy in
      a population-based cohort of older patients with kidney cancer. PATIENTS AND
      METHODS: Using the Surveillance, Epidemiology and End Results (SEER)-Medicare
      database, we identified patients aged >= 66 years who underwent partial or
      radical nephrectomy for localized kidney cancer diagnosed between 2000 and 2009.
      Primary outcomes were chest imaging (X-ray or computed tomography [CT]) and
      abdominal imaging (CT, MRI or ultrasonography) in Medicare claims from 4 to 36
      months after surgery. We estimated the frequency of imaging in three time periods
      (postoperative months 4-12, 13-24, 25-36), stratified by tumour stage. Repeated
      measures logistic regression was used to identify the patient and disease
      characteristics associated with imaging. RESULTS: Rates of chest imaging were 65
      80%, with chest X-ray surpassing CT in each time period. Rates of abdominal
      imaging were 58-76%, and cross-sectional imaging was more common than
      ultrasonography in each time period. Use of cross-sectional chest and abdominal
      imaging increased over time, while the use of chest X-ray decreased (P < 0.01).
      Ultrasonography use remained stable for patients with T1 and T2 disease, but the
      rate of use decreased in patients with T3 disease (P < 0.05). Rates of chest and
      abdominal imaging increased with tumour stage (P < 0.001). CONCLUSIONS: Patterns
      of imaging suggest possible overuse in patients at low risk of recurrence and
      underuse in those at greater risk. New surveillance imaging guidelines may reduce
      unwarranted variability and promote risk-based, cost-effective management after
      nephrectomy.

PMID- 25382745
TI  - The role of non-enhanced angiography in toe tip transfer with small diameter
      pedicle.
AB  - BACKGROUND: Toe tip transfer allows functional and esthetic reconstruction of the
      lost fingertip, but it is still uncommon because identification and dissection of
      donor and recipient veins can be challenging. Nonenhanced angiography (NEA) is a
      device that emits infrared light at a wavelength of 850 nm, which is exclusively
      absorbed by hemoglobin. The light penetrates the bones and other soft tissues,
      effectively visualizing veins in real time. The aim of this report is to present
      the experience on the preoperative use of nonenhanced angiography for
      visualization of donor and recipient veins in toe tip transfers in a series of
      patients. PATIENTS AND METHODS: Four cases of toe tip transfer and one case of
      free nail flap were performed for reconstruction of the tips of thumb and finger
      with preoperative examination using NEA. Patients' age ranged from 29 to 52 years
      old (average, 29.2 years old). Before the operation, the veins in the donor and
      recipient sites were marked using NEA, and the blood flow of the veins in the
      recipient site was confirmed. RESULTS: Pedicles in all transferred toe tips were
      less than 2 cm in length, with diameters smaller than 0.8 mm. The postoperative
      courses were uneventful, and all transferred toe tips survived completely, with
      satisfying functional and aesthetic results. CONCLUSIONS: NEA may facilitate
      venous dissection of the donor and the recipient sites, allowing safe and
      efficient toe tip transfer with a small pedicle.

PMID- 25382746
TI  - Improving the culture of safety on a high-acuity inpatient child/adolescent
      psychiatric unit by mindfulness-based stress reduction training of staff.
AB  - PROBLEM: The purpose of this study was to reduce perceived levels of
      interprofessional staff stress and to improve patient and staff safety by
      implementing a brief mindfulness-based stress reduction (MBSR) training program
      on a high-acuity psychiatric inpatient unit. METHODS: A one-group repeated
      measure design was utilized to measure the impact of the (MBSR) training program
      on staff stress and safety immediately post-training and at 2 months. Two
      instruments were utilized in the study: the Toronto Mindfulness Scale and the
      Perceived Stress Scale. FINDINGS: The MBSR program reduced staff stress across
      the 2-month post-training period and increased staff mindfulness immediately
      following the brief training period of 8 days, and across the 2-month post
      training period. A trend toward positive impact on patient and staff safety was
      also seen in a decreased number of staff call-ins, decreased need for 1:1
      staffing episodes, and decreased restraint use 2 months following the training
      period. CONCLUSIONS: A brief MBSR training program offered to an
      interprofessional staff of a high-acuity inpatient adolescent psychiatric unit
      was effective in decreasing their stress, increasing their mindfulness, and
      improving staff and patient safety.

PMID- 25382747
TI  - [(eta(5)-C5Me5)Ru](+) fragments ligated to polyaromatic hydrocarbons: an
      experimental and computational approach to pathways for haptotropic migration.
AB  - Ligand exchange reactions between [Cp*Ru(NCMe)3][PF6], where Cp* represents
      eta(5)-C5Me5, and the polycyclic aromatic hydrocarbons (PAHs) pyrene,
      acenaphthylene and fluoranthene afforded the known [Cp*Ru(eta(6)-pyrene)][PF6]
      (1) and the new mixed sandwiches [Cp*Ru(eta(6)-acenaphthylene)][PF6] (2) and
      [Cp*Ru(eta(6)-fluoranthene)][PF6] (3), respectively, isolated in quantitative
      yields (94-100%). Complex 3 is formed as a mixture of two isomers: 3A as the
      major product where the [Cp*Ru(+)] moiety is coordinated to the naphthalene
      fragment of fluoranthene, and 3B with the coordination of the arenophile to the
      peripheral benzene ring, in a 90/10 spectroscopic ratio. The composition and
      identity of the complexes were deduced by elemental analysis, (1)H and (13)C
      multidimensional NMR spectroscopy, and mass spectrometry. Compounds 1A, 3A and 2A
      have been characterized using X-ray structural investigations. That showed that
      the [Cp*Ru(+)] unit is eta(6)-attached to one of the two naphthalene rings in
      each complex. Heating 1 and 3 at 90  degrees C in CD3NO2 solutions or heating 3
      at 120  degrees C in the solid phase did not provide any evidence for thermally
      induced intramolecular inter-ring haptotropic rearrangements. These
      rearrangements were modelled by DFT calculations which indicated rather high
      activation energies.

PMID- 25382748
TI  - Challenging gender stereotypes: resistance and exclusion.
AB  - The likelihood of resisting gender-stereotypic peer group norms, along with
      expectations about personal resistance, was investigated in 9- to 10-year-olds
      and 13- to 14-year-olds (N = 292). Participants were told about a stereotype
      conforming group (boys playing football; girls doing ballet) and a stereotype
      nonconforming group (boys doing ballet; girls playing football). Contrary to
      expectations from gender-stereotyping research, participants stated that they
      would personally resist gender-stereotypic norms, and more so than they would
      expect their peers to resist. However, expecting peers to resist declined with
      age. Participants expected that exclusion from the group was a consequence for
      challenging the peer group, and understood the asymmetrical status of gender
      stereotypes with an expectation that it would be more difficult for boys to
      challenge stereotypes than for girls. 

PMID- 25382749
TI  - Sphingolipid metabolism and interorganellar transport: localization of
      sphingolipid enzymes and lipid transfer proteins.
AB  - In recent decades, many sphingolipid enzymes, sphingolipid-metabolism regulators
      and sphingolipid transfer proteins have been isolated and characterized. This
      review will provide an overview of the intracellular localization and topology of
      sphingolipid enzymes in mammalian cells to highlight the locations where
      respective sphingolipid species are produced. Interestingly, three sphingolipids
      that reside or are synthesized in cytosolic leaflets of membranes (ceramide,
      glucosylceramide and ceramide-1-phosphate) all have cytosolic lipid transfer
      proteins (LTPs). These LTPs consist of ceramide transfer protein (CERT), four
      phosphate adaptor protein 2 (FAPP2) and ceramide-1-phosphate transfer protein
      (CPTP), respectively. These LTPs execute functions that affect both the location
      and metabolism of the lipids they bind. Molecular details describing the
      mechanisms of regulation of LTPs continue to emerge and reveal a number of
      critical processes, including competing phosphorylation and dephosphorylation
      reactions and binding interactions with regulatory proteins and lipids that
      influence the transport, organelle distribution and metabolism of sphingolipids. 

PMID- 25382750
TI  - UBTD1 induces cellular senescence through an UBTD1-Mdm2/p53 positive feedback
      loop.
AB  - The tumour suppressor p53 plays an important role in tumourigenesis. Besides
      inducing apoptosis, it regulates cellular senescence, which constitutes an
      important barrier to tumourigenesis. The mechanism of regulation of cellular
      senescence by p53 and its downstream pathway are poorly understood. Here, we
      report that the ubiquitin domain-containing 1 (UBTD1) gene, a new downstream
      target of p53, induces cellular senescence and acts as a novel tumour suppressor
      by a mechanism that depends on p53. Expression of UBTD1 increased upon cellular
      senescence induced by serial passageing of cultures, as well as by exposure to
      DNA-damageing drugs that induce premature senescence. Over-expression of UBTD1
      induces senescence in human fibroblasts and cancer cells and attenuation of the
      transformed phenotype in cancer cells. UBTD1 is down-regulated in gastric and
      colorectal cancer tissues, and its lower expression correlates with a more
      aggressive phenotype and worse prognosis. Multivariate analysis revealed that
      UBTD1 expression was an independent prognostic factor for gastric cancer
      patients. Furthermore, UBTD1 increased the stability of p53 protein, by promoting
      the degradation of Mdm2 protein. Importantly, UBTD1 and p53 function mutually
      depend on each other in regulating cellular senescence and proliferation. Thus,
      our data suggest that, upon DNA damage, p53 induction by UBTD1 creates a positive
      feedback mechanism to further increase p53 expression. Our results establish
      UBTD1 as a regulator of cellular senescence that mediates p53 function, and
      provide insights into the mechanism of Mdm2 inhibition that impacts p53 dynamics
      during cellular senescence and tumourigenesis.

PMID- 25382751
TI  - Risk factors for hepatitis B and C infection among blood donors in five Chinese
      blood centers.
AB  - BACKGROUND: Few studies were conducted on hepatitis B and C virus (HBV and HCV,
      respectively) risk factors among Chinese blood donors in recent years since
      voluntary donors replaced commercial donors. STUDY DESIGN AND METHODS: A case
      control survey was conducted in HBV- or HCV-positive and -negative donors from
      five blood centers in China between September 2009 and April 2011. Case status
      was defined by having a reactive result on Monolisa HBsAg Ultra (Bio-Rad) for HBV
      and Ortho anti-HCV EIA 3.0 (Johnson & Johnson) for HCV. Controls were randomly
      selected qualified blood donors matched to cases by donation month and blood
      center. Specific test-seeking, medical-related, and behavioral risk factors were
      compared by HBV and HCV status using chi-square tests or Fisher's exact tests
      with Bonferroni correction. RESULTS: A total of 364 HBV cases, 174 HCV cases, and
      689 controls completed the survey; response rates were 66.2, 47.3, and 82%,
      respectively. HCV-positive donors were significantly more likely to report having
      a blood transfusion history (23.4% vs. 3.0%, p < 0.0001) and ever living with a
      person with illegal drug injection (6.0% vs. 0.5%, p < 0.0001) than controls.
      Having intravenous and intramuscular injections in the past 12 months and ever
      having a tattoo are marginal risk factors for HCV (p values < 0.01). No specific
      risk factor for HBV was identified. CONCLUSION: History of previous transfusion
      and living with illegal drug users are risk factors for HCV infection among
      Chinese blood donors from five regions. Test-seeking behavior is not associated
      with HBV or HCV infections.

PMID- 25382752
TI  - Efficient spray-coated colloidal quantum dot solar cells.
AB  - A colloidal quantum dot solar cell is fabricated by spray-coating under ambient
      conditions. By developing a room-temperature spray-coating technique and
      implementing a fully automated process with near monolayer control-an approach
      termed as sprayLD-an electronic defect is eliminated resulting in solar cell
      performance and statistical distribution superior to prior batch-processed
      methods along with a hero performance of 8.1%. 

PMID- 25382753
TI  - Venepuncture during head-up tilt testing in patients with suspected vasovagal
      syncope - implications for the test protocol.
AB  - BACKGROUND AND PURPOSE: Head-up tilt (HUT) testing is a widely used diagnostic
      tool in patients with suspected vasovagal syncope (VVS). However, no gold
      standard exists for this examination and the various protocols used have a
      limited sensitivity and specificity. Our aim was to determine the sensitivity of
      a sequential HUT testing protocol including venepuncture (VP) and sublingual
      nitroglycerin application. METHODS: This was a retrospective analysis of the
      diagnostic gain of a sequential HUT testing protocol including VP applied 10 min
      after the start of HUT testing and sublingual application of nitroglycerin 20 min
      after the start of the test protocol in 106 patients with a final diagnosis of
      VVS. The sensitivity of the test protocol was compared between patients with
      positive and negative history for VP induced VVS. RESULTS: Overall, pre-syncope
      or syncope occurred in 68 patients (64.2%). Only 17% of all patients fainted
      spontaneously within 10 min of passive HUT. Another 39.6% fainted within 20 min.
      Application of nitroglycerin after 20 min of HUT evoked syncope in another 7.5%
      until the end of 45 min of HUT. The sensitivity of the test protocol for evoking
      (pre-)syncope was 94.4% in patients with a positive history for VP associated VVS
      and 58% in patients with a negative history (P < 0.01**); 85.7% of patients with
      a positive history and 42.9% of patients with a negative history fainted within
      20 min of HUT testing (P < 0.01**). CONCLUSIONS: Implementation of VP in
      sequential HUT testing protocols allows the sensitivity of HUT testing to be
      increased, especially in patients with a positive history for VP associated VVS.

PMID- 25382755
TI  - Hyperbaric oxygen therapy for chronic radiation-induced tissue injuries:
      Australasia's largest study.
AB  - AIM: Chronic radiation injuries, although uncommon, are associated with poor
      quality of life in oncology patients. The present study assesses the efficacy and
      safety of hyperbaric oxygen therapy in the management of chronic radiation
      induced tissue injuries. METHODS: A retrospective analysis was performed in 276
      consecutive patients treated with hyperbaric oxygen therapy for chronic radiation
      induced tissue injuries at the Hyperbaric Medicine Unit, Townsville, Queensland,
      between March 1995 and March 2008. Of these patients, 189 (68%) had complete
      follow-up data and were assessed. RESULTS: A total of 265 events of chronic
      radiation tissue injury were experienced by the 189 patients treated with
      hyperbaric oxygen therapy. Osteoradionecrosis prophylaxis due to radiation
      induced dental disease had an overall response rate of 96% (P=0.00003; Wilcoxon
      matched-pairs signed-rank test). The overall response rates for established
      osteoradionecrosis of mandible, soft tissue necrosis of head and neck, and
      xerostomia were 86% (P=0.00001), 85% (P=0.002) and 64% (P=0.0001), respectively.
      The overall response rates for soft tissue necrosis at other sites, chronic
      radiation proctitis and hemorrhagic cystitis were 84% (P=0.03), 95% (P=0.0001)
      and 85% (P=0.03), respectively. The total complication rate after hyperbaric
      oxygen therapy was 15.9%, comprising reversible ear barotrauma (10.6%),
      reversible ocular barotrauma (4.2%), dental complications (0.5%) and myocardial
      infarction (0.5%). CONCLUSION: Our study demonstrates that hyperbaric oxygen
      therapy can be effectively used in a variety of chronic radiation-induced tissue
      injuries; its favorable risk profile suggests it should be considered for
      patients with radiation-induced tissue injuries.

PMID- 25382756
TI  - Synthesis of phosphorus-doped graphene and its wide potential window in aqueous
      supercapacitors.
AB  - Phosphorus-doped (P-doped) graphene with the P doping level of 1.30 at % was
      synthesized by annealing the mixture of graphene and phosphoric acid. The
      presence of P was confirmed by elemental mapping and X-ray photoelectron
      spectroscopy, while the morphology of P-doped graphene was revealed by using
      scanning electron microscopy and transmission electron microscopy. To investigate
      the effect of P doping, the electrochemical properties of P-doped graphene were
      tested as a supercapacitor electrode in an aqueous electrolyte of 1 M H2 SO4. The
      results showed that doping of P in graphene exhibited significant improvement in
      terms of specific capacitance and cycling stability, compared with undoped
      graphene electrode. More interestingly, the P-doped graphene electrode can
      survive at a wide voltage window of 1.7 V with only 3 % performance degradation
      after 5000 cycles at a current density of 5 A g(-1), providing a high energy
      density of 11.64 Wh kg(-1) and a high power density of 831 W kg(-1).

PMID- 25382758
TI  - All doctors are jackasses.

PMID- 25382757
TI  - Evaluation of the selective glucocorticoid receptor agonist compound A for
      ototoxic effects.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the selective glucocorticoid receptor agonist
      (SEGRA) compound A, a potential novel therapeutic for inner ear disorders, for
      ototoxic effects. STUDY DESIGN: Laboratory animal study. METHODS: Experimental
      guinea pigs were grouped as follows: Systemic application of compound A (1.5
      mg/kg and 4.5 mg/kg; n = 6/group) and intratympanic application of compound A (1
      mM and 10 mM; n = 6/group). Contralateral ears in topically treated animals
      served as controls. Hearing thresholds were determined by auditory brainstem
      response before and directly after the application of compound A, as well as on
      days 3, 7, 14, 21, and 28. At the end of the experiments, temporal bones were
      harvested for histological evaluation. RESULTS: Systemic administration of
      compound A (1.5 mg/kg and 4.5 mg/kg) did not cause hearing threshold shifts,
      whereas the intratympanic injection (1 mM and 10 mM) resulted in a hearing loss.
      Histological analysis of the middle and inner ears after topical compound A
      application showed alterations in the tympanic membranes, the auditory ossicles,
      and the round window membranes, whereas spiral ganglion cells and hair cells were
      not affected. CONCLUSION: SEGRAs such as compound A could provide novel
      therapeutic options for the treatment of inner ear disorders and reduce metabolic
      side effects. Whereas the intratympanic application of compound A resulted in a
      hearing loss, the systemic application of compound A merits evaluation for
      otoprotective effects in trauma models.

PMID- 25382759
TI  - Readily prepared dynamic hydrogels by combining phenyl boronic acid- and maltose
      modified anionic polysaccharides at neutral pH.
AB  - Dynamic covalent hydrogels are facilely prepared from biocompatible
      polysaccharides in physiological conditions by the formation of phenylboronate
      ester cross-links. This is based on the simple mixing of carboxylate-containing
      polysaccharides (i.e., hyaluronic acid or carboxymethylcellulose) modified with
      phenylboronic acid and maltose moieties according to mild coupling reactions
      performed in aqueous solution. The formation of dynamic networks based on
      reversible boronic-ester cross-links is demonstrated by analyzing their
      rheological behavior. This study shows that these gels can adapt their structure
      in response to chemical stimuli such as variations in pH or addition of glucose
      and self-heal.

PMID- 25382761
TI  - Ectopic folliculosebaceous units at the coronal sulcus.
AB  - Tyson glands were described in the 17th century as modified sebaceous glands of
      the coronal sulcus of the penis. However, this description and other early texts
      supporting the existence of Tyson glands were not accompanied by illustrations.
      The existence of such glands has been passing through the literature without
      adequate graphical demonstration, which has contributed to controversial debates.
      Herein we present a case of a partial penectomy performed on a 65-year-old man
      with a squamous cell carcinoma of the penis. In this case we identified sebaceous
      glands as well as folliculosebaceous units in the coronal sulcus. We also
      comparatively examined 12 cases of partial penectomy to search for sebaceous
      glands or folliculosebaceous units in the coronal sulcus or the preputium. We
      found neither sebaceous glands nor folliculosebaceous units at the coronal sulcus
      or the mucosal aspect of the prepuce. We conclude that: (1) folliculosebaceous
      units are possible in the coronal sulcus, as the current case illustrates for the
      first time in literature and (2) the current case is an oddity, probably induced
      by the accompanying squamous cell carcinoma, and therefore it may represent an
      ectopic folliculosebaceous unit rather than an anatomic variation. 

PMID- 25382763
TI  - Evaluation of novel resorbable membranes for bone augmentation in a rat model.
AB  - OBJECTIVES: Our study compared two novel, biodegradable poly(trimethylene
      carbonate) (PTMC) barrier membranes to clinically applied barrier membranes in
      maintaining volume of block autologous bone grafts in a rat mandible model.
      MATERIAL AND METHODS: Two hundred and forty rats were included in this study.
      Block autologous bone grafts of 5 mm in diameter were harvested from the
      mandibular angles and transplanted onto the contralateral side. The bone grafts
      were either covered with a membrane or left uncovered. The applied membranes
      included pure PTMC membranes, biphasic calcium phosphate (BCP) incorporated PTMC
      composite membranes, expanded poly(tetrafluoroethylene) (e-PTFE) membranes (Tex)
      and collagen membranes (Geistlich Bio-Gide). After 2, 4 and 12 weeks, the rat
      mandibles were retrieved and analysed by histological evaluation and MUCT
      quantification. RESULTS: The histological evaluation revealed that in time the
      block autologous bone graft was well integrated to the recipient bone via
      gradually maturing newly formed bone and did not show signs of resorption,
      independent of membrane coverage or types of membrane. MUCT quantification showed
      the volume of the bone graft and recipient bone together was maintained by new
      bone formation and recipient bone resorption. CONCLUSIONS: Our study showed that
      the use of PTMC membranes and PTMC-BCP composite membranes resulted in similar
      bone remodelling to the collagen membranes and e-PTFE membranes and that the use
      of barrier membranes did not interfere with bone remodelling of the bone grafts
      and recipient bones. However, the used barrier membranes seemed not to contribute
      in maintaining the volume of block autologous bone grafts.

PMID- 25382762
TI  - Functional classification of BRCA2 DNA variants by splicing assays in a large
      minigene with 9 exons.
AB  - Numerous pathogenic DNA variants impair the splicing mechanism in human genetic
      diseases. Minigenes are optimal approaches to test variants under the splicing
      viewpoint without the need of patient samples. We aimed to design a robust
      minigene construct of the breast cancer gene BRCA2 in order to investigate the
      impact of variants on splicing. BRCA2 exons 19-27 (MGBR2_ex19-27) were cloned in
      the new vector pSAD. It produced a large transcript of the expected size (2,174
      nucleotides) and exon structure (V1-ex19-27-V2). Splicing assays showed that 18
      (17 splice-site and 1 silencer variants) out of 40 candidate DNA variants induced
      aberrant patterns. Twenty-four anomalous transcripts were accurately detected by
      fluorescent-RT-PCR that were generated by exon-skipping, alternative site usage,
      and intron-retention events. Fourteen variants induced major anomalies and were
      predicted to disrupt protein function so they could be classified as pathogenic.
      Furthermore, minigene mimicked previously reported patient RNA outcomes of seven
      variants supporting the reproducibility of minigene assays. Therefore, a relevant
      fraction of variants are involved in breast cancer through splicing alterations.
      MGBR2_ex19-27 is the largest reported BRCA2 minigene and constitutes a valuable
      tool for the functional and clinical classification of sequence variations.

PMID- 25382764
TI  - Climbing therapy under PK-tailored prophylaxis.
AB  - Climbing has a low risk of injury and strengthens the entire musculature. Due to
      its benefits in physical and mental health as well as its high fun factor
      climbing is an established way of therapy. So far, the usefulness of climbing
      therapy has not been shown for people with haemophilia (PWH). A crucial
      requirement for physical activity in PWH is regular prophylaxis. As the patient's
      individual pharmacokinetic (PK) response varies significantly, PK-tailored
      prophylaxis may decrease bleeding frequency. CASE REPORT: We describe a man (age
      25 years) with severe haemophilia A who took part in an 8.5-month weekly climbing
      program under PK-tailored prophylaxis. Bleeding frequency, factor consumption,
      joint health (Haemophilia Joint Health Score, HJHS), quality of life (Haemo-QoL
      A) and climbing performance (UIAA scale) were assessed before and after the
      training. Prior to the study, the patient was on demand treatment. The patient
      was started on standard prophylaxis for a 2 months period and then observed for
      6.5 months under PK-tailored prophylaxis. PK-tailored prophylaxis was targeted to
      a trough level of 1-3%. For high-impact activities a factor activity >15%, for
      low-impact activities a factor activity >5% was suggested. RESULTS: Climbing
      therapy was safe. The bleeding rate decreased from 14 (2012) to 1 (during the
      study period of 8.5 months). The one bleeding event was due to a missed infusion
      and was not triggered by physical activity. The elimination half-life using
      Bayesian statistics was determined to be 16h. Using this half-life for PK
      tailored prophylaxis reduced the factor VIII consumption in comparison to
      standard prophylaxis. Joint health was particularly improved in the categories
      range of motion and swelling. Quality of life scores stayed at a high level.
      Climbing performance improved by 1 grade. CONCLUSION: The combination of PK
      tailored prophylaxis with therapeutic climbing improved clinical outcome in this
      young adult with severe haemophilia. The tailored concept for high- and low
      impact activities appeared to be safe.

PMID- 25382765
TI  - Treatment options for haemophilic arthropathy of the elbow after failed
      conservative therapy. A single centre experience.
AB  - After ankle and knee, the elbow is the most frequent joint affected by
      haemophilic arthropathy. The objective of this retrospective single centre study
      is to evaluate the results of treatment of elbow arthropathy after failed
      conservative therapy. PATIENTS, METHODS: In 21 consecutive patients, 11
      radiosynoviortheses (RSO), four arthroscopic and six open synovectomies were
      performed, among them four with additional resection of the radial head. The mean
      duration of follow-up was 4.8 (RSO) and 5.3 years (surgery), respectively. Pain
      status (visual analogue scale, VAS), bleeding frequency, range of motion (ROM) as
      well as patient satisfaction were evaluated. RESULTS: Both, RSO and surgical
      synovectomy, achieved a significant reduction of pain and bleeding frequency (p <
      0.05). Surgical synovectomies were associated with a marked yet not statistically
      significant increase of postoperative ROM. Radial head resection improved forearm
      rotation in all cases. No complications occurred. 20 out of 21 patients were
      satisfied or highly satisfied with the result of the treatment and would undergo
      the respective procedure again. CONCLUSION: Due to the effectiveness and safety
      RSO is considered to be the primary treatment option in haemophilic arthropathy
      of the elbow after failed conservative therapy. Arthroscopic synovectomy should
      be considered if RSO shows inadequate effect or in the presence of
      contraindications. Open synovectomy with resection of the radial head yields good
      results in the case of advanced arthropathy with radial head impingement.

PMID- 25382766
TI  - Elective total knee arthroplasty in haemophilic patients. Proposal for a clinical
      pathway.
AB  - Total knee arthroplasty (TKA) provides significant pain relief and better
      function in patients with end-stage haemophilic knee arthropathy. Peri- and
      postoperative care tends to be more complex than in non-haemophilic patients
      undergoing TKA and requires a multidisciplinary team approach. AIM: The
      implementation of standardized clinical pathways in non-haemophilic patients
      undergoing TKA has been shown to increase quality of care and to reduce
      postoperative complication rates. Consequently, the use of clinical pathways in
      haemophilic patients undergoing TKA may be beneficial to this particular
      subpopulation of patients. METHODS: A clinical pathway for TKA for haemophilic
      patients was designed in a consensus process involving all participating
      departments. RESULTS: We propose a specifically adjusted clinical pathway for TKA
      for haemophilic patients to show that standardization of elective orthopaedic
      surgery in haemophilia is feasible. CONCLUSION: The authors emphasize that there
      are limitations on categorizing haemophilic patients and stress that individual
      interdisciplinary treatment should take precedence over a standardized approach.

PMID- 25382767
TI  - Risks and challenges of orthopaedic invasive interventions in haemophilia in a
      low-resource country. A single-center experience.
AB  - Haemophilic arthropathy is a defining feature and a debilitating condition of
      persons with haemophilia (PwH) in low resource countries. Orthopaedic surgery is
      unavoidable for patients with high occurrence of joint damage. AIMS: We aimed to
      evaluate the spectrum and outcome of invasive orthopaedic therapies in PwH and
      von Willebrand diseases (VWD). PATIENTS AND METHODS: Our descriptive
      observational retrospective study included 131 invasive surgical procedures,
      performed on 76 consecutive patients, most of them (93.4%) with severe disease,
      treated in Timisoara's Haemophilia Center over a period of 12 years; 17.1% had
      pre-operation anti-FVIII inhibitors. Invasive elective procedures were
      predominant (90.8%) as compared to emergency measures (9.2%); according to their
      invasiveness, 20.6% of interventions were major, 44.3% intermediate and 35.1%
      minor. Results were good in the majority of cases; significantly reduced joint
      bleed rate and pain score were the most consistent achievements. The greatest
      proportion of complications occurred after major (66.7%), compared to moderate
      (25.6%) and minor (7.7%) interventions. The main threatening complication was the
      development (3.8%) or increase (4.6%) of inhibitor titer. Local bacterial
      infections and wound dehiscence complicated the evolution in 4.6% and 0.8 % of
      cases, respectively; we noticed no blood-borne infections or thrombotic
      accidents. Low dosage (10.7%) and short duration of substitution (21.4%) led to
      increased post-surgical bleeding and post-haemorrhagic anaemia. CONCLUSIONS:
      Surgery is a highly demanding intervention in haemophilia, which cannot be
      ignored in a low resource country. It represents a life or limb-saving and
      quality of life-improving measure.

PMID- 25382768
TI  - [Age-related activation of the muscles during upright standing in patients with
      haemophilia].
AB  - Thehaemophilicarthropathyaffects thefunction of theknee joint muscles. The aim of
      thisstudywas to investigatethe myoelectrical signal ofknee jointmusclesin
      different agestages during upright standing. Surface EMG (SEMG) amplitudes of
      quadriceps, hamstrings and gastrocnemii were measured in 191 patients with severe
      haemophilia A (n=164) and B (n=27) while standing on an even surface. After an
      age-based classification of patients into the subgroups H(A): 17-29 (n = 37),
      H(B): 30-39 (n = 50), HC: 40-49 (n = 61), H(D): 50-70 in years (n = 43) the
      clinical WFH score for the ankle and knee joint was determined. To normalize the
      SEMG values amplitude ratios (percentage of cumulated activity) were calculated
      with respect to the specific limb. With increasing age, the patient showed
      descriptively a deterioration of the joint situation. The extensors of the knee
      joint reached significantly higher absolute and percentage levels in the muscle
      activity with increasing age (p < 0.05). The absolute amplitude values of the Mm.
      gastrocnemii showed no differences in the age groups while the relative levels
      were decreased. The present study shows that patients with increasing age and
      degree of haemophilic arthropathy develop a modified control strategy during
      upright standing, in the form of a shift from the plantar flexors to the
      extensors of the knee joint.

PMID- 25382769
TI  - [Food consumption and dietary behaviour in haemophilia patients before and after
      a nutrition consultation].
AB  - In over two-thirds of deaths, nutrition is a determining factor. Nutritional
      condition and dietary recommandations are unspecified in the haemophilia
      treatment. Aim of this study was to examine the food consumption and dietary
      behaviour in affected patients before and after a nutrition consultation.
      PATIENTS, METHODS: Data were assessed via questionnaires and compared between 38
      patients with haemophilia (PwH) and 20 controls without haemophilia. Furthermore,
      in a randomised controlled trial 11 patients with haemophilia (PwH-I) took part
      in an adapted nutrition consultation and were supervised over six months as
      opposed to 12 patients with haemophilia (PwH-O) without intervention. PwH were
      compared to controls more pleased with their weight (53 vs. 40%), used more
      nutrition consultations in the past (53 vs. 15%) and consumed more dairy products
      (40 vs. 15%) and fruits (45 vs. 30%). RESULTS: After nutrition consultation PwH-I
      were better informed about their own blood values than PwH-O. The nutrition rated
      high in both groups, but PwH-I were more mindful of the feeling of satiety (9 vs.
      36%) compared to PwH-O (33 vs. 17%). Moreover, PwH-I ate less under stress and/or
      out of boredom, showed a higher satisfaction regarding their weight and increased
      the liquid intake (55 vs. 73%), which remained unchanged in PwH-O with 42%.
      Compared to PwH-O, PwH-I ate more roughage, low-fat food, fish and fruits,
      therefore consuming less coffee/tea. CONCLUSION: Food consumption and dietary
      behaviour are similar between patients with haemophilia and controls without
      haemophilia. A nutrition consultation affected the food consumption and dietary
      behaviour in patients with haemophilia positively and can consequently contribute
      to preservation of health and prevention of nutritional diseases.

PMID- 25382770
TI  - Clot waveform analysis in patients with haemophilia A.
AB  - Clot waveform analysis extends the interpretation of aPTT measurement curves. The
      curve is mathematically processed to obtain information about fibrin formation
      kinetics including semiquantitative determination of thrombin, prothrombinase and
      tenase activity. PATIENTS, METHOD: In this study the feasibility of clot waveform
      analysis for monitoring of haemophilia A was investigated using blood samples
      from healthy controls as well as haemophilia A patients under various clinical
      conditions. RESULTS: Thrombin, prothrombinase and tenase activity show a high
      correlation to factor VIII levels. Tenase activity was found to exhibit a linear
      relationship to factor VIII levels over a very large concentration range and was
      able to discriminate patients with severe, moderate and mild haemophilia.
      CONCLUSION: Clot waveform analysis is an easy, fast and cheap method to access
      disturbances in clot formation and can be done without any additional
      measurements beside an aPTT.

PMID- 25382771
TI  - Successful second ITI with factor IX and combined immunosuppressive therapy. A
      patient with severe haemophilia B and recurrence of a factor IX inhibitor.
AB  - Immune tolerance induction (ITI) in patients with haemophilia B and inhibitors
      may be complicated by anaphylactic reactions and nephrotic syndrome with lower
      success rates than in haemophilia A (25% vs. 50-90%). According to case reports,
      immunosuppressive therapy in addition to high doses of factor IX (FIX) appears to
      be promising. We report an 18-year-old patient with severe haemophilia B and a
      FIX inhibitor with a maximum titre of 2.6 Bethesda units and allergic skin
      reactions to FIX infusions. At 5 years of age, this patient already had a FIX
      inhibitor with allergic reactions to FIX and activated prothrombin complex
      concentrate. ITI at 11 years of age with high-dose FIX, dexamethasone, rituximab,
      mycophenolate mofetil and intravenous immunoglobulins had induced a sustained
      response until the current presentation. The patient was restarted on the same
      ITI regimen with aforementioned immunosuppressants, which were initiated one week
      before high-dose FIX. No allergic reactions, nephrotic syndrome or serious
      infection occurred during ITI. The FIX inhibitor was undetectable after five
      weeks of treatment and remained so until 19 months of follow-up. 

PMID- 25382772
TI  - Significance of platelet function diagnostics for clarification of suspected
      battered child syndrome.
AB  - The manifestation of an unclear bleeding tendency in childhood calls for an
      extended coagulation work-up, particularly when a battered child syndrome is
      suspected and typical concomitant injuries are absent. The chosen diagnostic
      tests should be able to detect the presence of relatively common coagulation
      defects such as von Willebrand syndrome or hemophilia, but also rare diseases
      such as inherited thrombocytopathies. The PFA-100(r) test does not help to
      provide a definite diagnosis especially in cases of mild inherited
      thrombocytopathies, since in most cases the PFA-100(r) test results are normal.
      For this purpose, specific platelet function testing is needed. However, the
      methods are only available in some coagulation laboratories. Also, other
      limitations need to be taken into consideration such as pre-analytical problems
      and difficulties in the interpretation of test results especially in infants. We
      present two cases that were diagnosed with an aspirin-like defect as an inherited
      thrombocytopathy, even though their PFA-100 closure times were within the normal
      range. Based on pathological findings in the platelet aggregometry test, this
      diagnosis could be made.

PMID- 25382773
TI  - Successful thrombolytic treatment of neonatal arterial thromboses.
AB  - Compared to children of other age groups neonates show an increased thrombotic
      risk. The acute therapy depends on thrombus age, the localisation of vascular
      occlusion and the severity of the underlying disease. The treatment of choice is
      represented by the administration of unfractionated (UFH) or low molecular weight
      heparin (LMWH). If loss of limbs or organs is imminent, the application of
      thrombolytic treatment with recombinant tissue-type plasminogen activator (rt-PA)
      should be considered whilst taking into account the associated bleeding risk. We
      report on two patients in which thrombolytic therapy has been conducted
      successfully. 

PMID- 25382775
TI  - Photoluminescence of monolayer MoS2 on LaAlO3 and SrTiO3 substrates.
AB  - In an atomically thin-film/dielectric-substrate heterostructure, the elemental
      physical properties of the atomically thin-film are influenced by the interaction
      between the thin-film and the substrate. In this article, utilizing monolayer
      MoS(2) on LaAlO(3) and SrTiO(3) substrates, as well as SiO2 and Gel-film as
      reference substrates similar to previously reported work [Nano Res, 2014, 7,
      561], we systematically investigate the substrate effect on the photoluminescence
      of monolayer MoS(2). We observed significantly substrate-dependant
      photoluminescence of monolayer MoS(2), originating from substrate-to-film charge
      transfer. We found that SiO2 substrate introduces the most charge doping while
      SrTiO(3) introduces less charge transfer. Through the selection of desired
      substrate, we are able to induce different amounts of charge into the monolayer
      MoS(2), which consequently modifies the neutral exciton and charged exciton
      (trion) emissions. Finally, we proposed a band-diagram model to elucidate the
      relation between charge transfer and the substrate Fermi level and work function.
      Our work demonstrates that the substrate charge transfer exerts a strong
      influence on the monolayer MoS(2) photoluminescence property, which should be
      considered during device design and application. The work also provides a
      possible route to modify the thin-film photoluminescence property via substrate
      engineering for future device design.

PMID- 25382774
TI  - Inhibitor development and management in three non-severe haemophilia A patients
      with T295A variant.
AB  - Missense mutations are the most common F8 gene defects among the patients with
      non-severe haemophilia A. This type of mutation is typically associated with low
      (5%) inhibitor risk. In the present retrospective study we analysed the clinical
      data of 16 haemophiliacs with the T295A missense mutation treated at Bonn
      Haemophilia Centre. In total, three patients developed inhibitors: two patients
      experienced low-titer and one high-titer inhibitors. Both patients with low titer
      inhibitors underwent successful ITI. The third patient, at the age of 81,
      developed initially low-titer inhibitors (3 BU/ml) after rFVIII therapy because
      of knee surgery. He experienced spontaneous multiple large skin haematomas and
      haemarthrosis. Immunosuppressive therapy was not applicable because of the
      infectious origin of discitis (Th3-Th4). Immunoadsorption was performed, but the
      inhibitor titer increased up to 42 BU/ml nine weeks after termination. A
      successful treatment of discitis with antibiotics finally allowed a weekly
      therapy (four times) with rituximab (375 mg/m(2)). This resulted in a decrease of
      inhibitor titre to 0.7 BU/ml eight weeks after the fourth rituximab application.
      Patient had endogenous FVIII levels of 3-5%. Twelve months after rituximab
      therapy (after B cells recovery) he relapsed with low-titer inhibitors and
      therefore was treated with single rituximab dose (375 mg/m(2)) again. This
      resulted in his depletion of B cells, measurable endogenous FVIII levels and non
      measurable inhibitors. This study demonstrated T295A variant to be associated
      with significantly increased (3/16 patients, 17%) inhibitor development.

PMID- 25382776
TI  - Getting what you paid for in quality control? Cell lines exemplify a more general
      challenge.

PMID- 25382778
TI  - Is microbial gardening a food gamble or a safe bet? (Comment on DOI
      10.1002/bies.201400100).

PMID- 25382779
TI  - Lysine methylation in cancer: SMYD3-MAP3K2 teaches us new lessons in the Ras-ERK
      pathway.
AB  - Lysine methylation has been traditionally associated with histones and
      epigenetics. Recently, lysine methyltransferases and demethylases - which are
      involved in methylation of non-histone substrates - have been frequently found
      deregulated in human tumours. In this realm, a new discovery has unveiled the
      methyltransferase SMYD3 as an enhancer of Ras-driven cancer. SMYD3 is up
      regulated in different types of tumours. SMYD3-mediated methylation of MAP3K2
      increases mutant K-Ras-induced activation of ERK1/2. Methylation of MAP3K2
      prevents it from binding to the phosphatase PP2A, thereby impeding the impact of
      this negative regulator on Ras-ERK1/2 signals, leading to the formation of lung
      and pancreatic adenocarcinomas. Furthermore, depletion of SMYD3 synergises with a
      MEK inhibitor, currently in clinical trials, to block Ras-driven pancreatic
      neoplasia. These results underscore the importance of lysine methylation in the
      regulation of signalling pathways relevant for tumourigenesis and endorse the
      development of drugs targeting unregulated lysine methylation as therapeutic
      agents in the struggle against cancer. 

PMID- 25382780
TI  - The alien replicon: Artificial genetic constructs to direct the synthesis of
      transmissible self-replicating RNAs: In vivo synthesised heterologous (alien) RNA
      constructs are capable of initiating self-replication following transmission to
      the host organism.
AB  - Artificial genetic constructs that direct the synthesis of self-replicating RNA
      molecules are used widely to induce gene silencing, for bioproduction, and for
      vaccination. Interestingly, one variant of the self-replicon has not been
      discussed in the literature: namely, transgenic organisms that synthesise alien
      replicons. For example, plant cells may be easily genetically modified to produce
      bacteriophages or insect viruses. Alien replicon-producing organisms (ARPOs) may
      serve as a unique tool for biocontrol or to selectively influence the
      characteristics of a target organism. The ARPO approach would have to meet strict
      biosafety criteria, and its practical applications are problematic. However, a
      discussion on ARPO applicability would be valuable to outline the full set of
      options available in the bioengineering toolbox. In this paper, RNA replicons for
      bioengineering are reviewed briefly, and the ARPO approach is discussed. 

PMID- 25382781
TI  - Pre-birth world and the development of the immune system: mum's diet affects our
      adult health: new insight on how the diet during pregnancy permanently influences
      offspring health and immune fitness.
AB  - Secondary lymphoid organs form in utero through an inherited and well-established
      developmental program. However, maternal non-heritable features can have a major
      impact on the gene expression of the embryo, hence influencing the future health
      of the offspring. Recently, maternal retinoids were shown to regulate the
      formation of immune structures, shedding light on the role of maternal nutrition
      in the genetic signature of emergent immune cells. Here we highlight evidence
      showing how the maternal diet influences the establishment of the immune system,
      and we also discuss how unbalanced maternal diets may set the response to
      infection and vaccination in the progeny. 

PMID- 25382786
TI  - A novel photo-responsive azobenzene-containing nanoring host for fullerene-guest
      facile encapsulation and release.
AB  - Azobenzenes in particular have been proved to have a robust photo-response, in
      which their configuration can transform between the trans- and cis-form upon UV
      visible irradiation. Accordingly, azobenzene-containing molecules are frequently
      applied in the design of the guests, involving so-called host-guest chemistry. In
      this paper, a novel photo-responsive nanoring host molecule ([4]AB) has been
      designed by introducing four azobenzene groups onto the ring, and interactions
      between the designed nanoring host and fullerenes C60 and C70 guests were
      investigated at both the M06-L/MIDI! as well as M06-2X/6-31G(d) level of theory.
      By analyzing the geometric characteristics and host-guest binding energies, it is
      revealed that the designed [4]AB with diameter ca. 13.4 A is an ideal host
      molecule for the encapsulation of guests C60 and C70 fullerene. Meanwhile,
      inferred from UV-vis-NIR spectroscopy, the guest C60 and C70 could be facilely
      released from the cavity of the [4]AB via configuration transformation between
      trans- and cis-form of the host under 474 and 506 nm photo-irradiation,
      respectively. Frontier orbital features, weak interaction regions, infrared
      spectroscopy and (1)H NMR spectra have also been theoretically simulated. The
      present work would provide a new strategy for facile reversible encapsulation and
      release of fullerene guest by a novel nanoring host. 

PMID- 25382788
TI  - Introduction: identifying and assessing conservation opportunity.

PMID- 25382789
TI  - Optimizing of the basophil activation test: Comparison of different basophil
      identification markers.
AB  - Background Flowcytometric identification of basophils is a prerequisite for
      measuring activation of basophils with IgE-dependent or IgE-independent stimuli.
      Aim of this study was to compare different marker combinations in a simultaneous
      multicolor flowcytometric measurement. Methods Ten patients with a grass pollen
      allergy and 3 controls were included in the study. Basophilic cells were gated by
      using anti-CCR3647, anti-IgE, anti-CRTH2, anti-CD203c und anti-CD3. Cells were
      activated by a monoclonal anti-FcepsilonRI antibody, N-formyl-methionyl-leucyl
      phenylalanine (fMLP) and the allergen extract Phleum pratense. The activation
      marker anti-CD63 was used. Results The highest relative number of basophils was
      found with anti-CCR3+ cells, anti-IgE+ and anti-IgE+ /anti-CD203c+ cells, the
      lowest with CRTH2+ /CD203c+ /CD3- cells. A very good and good concordance of
      CCR3+ cells was seen with CCR3+ /CD3- cells and CRTH2+ /CD203c+ /CD3- cells in
      all experiments. The contamination of the CCR3+ population with CD3+ cells and
      the contamination of the IgE+ -population with CCR3- cells and CD203- cells were
      the lowest compared to all other marker combinations. Conclusions As the highest
      relative number of basophils was identified by anti-CD193 (CCR3) followed by the
      anti-IgE and anti-IgE/antiCD203c positive population in most cases, these markers
      can generally be recommended for identification of basophils. If a basophil
      population with very high purity is needed, anti-IgE should be chosen. (c) 2014
      Clinical Cytometry Society.

PMID- 25382790
TI  - NH3-promoted ligand lability in eleven-vertex rhodathiaboranes.
AB  - The reaction of the 11-vertex rhodathiaborane, [8,8-(PPh3)2-nido-8,7-RhSB9H10]
      (1), with NH3 affords inmediately the adduct, [8,8,8-(NH3)(PPh3)2-nido-8,7
      RhSB9H10] (4). The NH3-Rh interaction induces the labilization of the PPh3
      ligands leading to the dissociation product, [8,8-(NH3)(PPh3)-nido-8,7-RhSB9H10]
      (5), which can then react with another molecule of NH3 to give [8,8,8
      (NH3)2(PPh3)-nido-8,7-RhSB9H10] (6). These clusters have been characterized in
      situ by multielement NMR spectroscopy at different temeperatures. The variable
      temperature behavior of the system demonstrates that the intermediates 4-6 are in
      equilibrium, involving ligand exchange processes. On the basis of low intensity
      signals present in the (1)H NMR spectra of the reaction mixture, some species are
      tentatively proposed to be the bis- and tris-NH3 ligated clusters, [8,8-(NH3)2
      nido-8,7-RhSB9H10] (7) and [8,8,8-(NH3)3-nido-8,7-RhSB9H10] (8). After
      evaporation of the solvent and the excess of NH3, the system containing species 4
      8 regenerates the starting reactant, 1, thus closing a stoichiometric cycle of
      ammonia addition and loss. After 40 h at room temperature, the reaction of 1 with
      NH3 gives the hydridorhodathiaborane, [8,8,8-(H)(PPh3)2-nido-8,7-RhSB9H9] (2), as
      a single product. The reported rhodathiaboranes show reversible H3N-promoted
      ligand lability, which implies weak Rh-N interactions, leading to a rare case of
      metal complexes that circumvent "classical" Werner chemistry. 

PMID- 25382787
TI  - Developmental changes in brain function underlying inhibitory control in autism
      spectrum disorders.
AB  - The development of inhibitory control-the ability to suppress inappropriate
      actions in order to make goal-directed responses-is often impaired in autism
      spectrum disorders (ASD). In the present study, we examined whether the
      impairments in inhibitory control evident in ASD reflect-in part-differences in
      the development of the neural substrates of inhibitory control from adolescence
      into adulthood. We conducted a functional magnetic resonance imaging (fMRI) study
      on the anti-saccade task, a probe of inhibitory control, in high-functioning
      adolescents and adults with ASD compared to a matched group of typically
      developing (TD) individuals. The ASD group did not show the age-related
      improvements in behavioral performance from adolescence to adulthood evident in
      the typical group, consistent with previous behavioral work. The fMRI results
      indicated that much of the circuitry recruited by the ASD group was similar to
      the TD group. However, the ASD group demonstrated some unique patterns,
      including: (a) a failure to recruit the frontal eye field during response
      preparation in adolescence but comparable recruitment in adulthood; (b) greater
      recruitment of putamen in adolescence and precuneus in adolescence and adulthood
      than the TD group; and (c) decreased recruitment in the inferior parietal lobule
      relative to TD groups. Taken together, these results suggest that brain circuitry
      underlying inhibitory control develops differently from adolescence to adulthood
      in ASD. Specifically, there may be relative underdevelopment of brain processes
      underlying inhibitory control in ASD, which may lead to engagement of subcortical
      compensatory processes.

PMID- 25382791
TI  - C5-C10 directly bonded tetrodotoxin analogues: possible biosynthetic precursors
      of tetrodotoxin from newts.
AB  - The identification of novel tetrodotoxin (TTX, 1) analogues would significantly
      contribute to the elucidation of its biosynthetic pathway. In this study, the
      first C5-C10 directly bonded TTX analogues, 4,9-anhydro-10-hemiketal-5-deoxyTTX
      (2) and 4,9-anhydro-8-epi-10-hemiketal-5,6,11-trideoxyTTX (3), were found in the
      newt Cynops ensicauda popei by using a screening method involving HILIC-LC-MS/MS
      focused on the fragment ions of TTX analogues, and their structures were
      elucidated by spectroscopic methods. Compound 2 was detected in a wide range of
      newt species, and the 2 and TTX contents of 22 newt specimens were correlated (rs
      =0.88). Based on these results and its structural features, 2 was predicted to
      serve as a precursor of TTX that would be directly converted into 4,9-anhydroTTX
      (4) by Baeyer-Villiger-like oxidation or via 4,9-anhydro-5-deoxyTTX formed by
      cleavage of the C5-C10 bond. The bicyclic carbon skeletons of 2 and 3 suggested a
      possible monoterpene origin for TTX. 

PMID- 25382792
TI  - The role of hematopoietic stem cell transplantation for relapsed and refractory
      Hodgkin lymphoma.
AB  - The optimal treatment strategy with the use of hematopoietic stem cell
      transplantation (HSCT) for relapsed and refractory Hodgkin lymphoma (HL) remains
      unclear. We performed a retrospective analysis using registry data from the
      Japanese Society for Hematopoietic Cell Transplantation. Adult patients with HL
      who underwent a first autologous or a first allogeneic HSCT between 2002 and 2009
      were included. Patients who underwent HSCT in first complete remission (CR) were
      excluded. Autologous and allogeneic HSCT were performed in 298 and 122 patients,
      respectively. For autologous HSCT, overall survival at 3 years (3yOS) was 70%,
      and sex, age, disease status, and performance status (PS) at HSCT were prognostic
      factors. OS was favorable even in patients who underwent autologous HSCT in
      disease status other than CR. For allogeneic HSCT, 3yOS was 43%, and sex and PS
      at HSCT were prognostic factors. Disease status at HSCT, previous autologous
      HSCT, and conditioning intensity did not affect OS. Moreover, graft-versus-host
      disease did not affect progression-free survival or relapse/progression rate. A
      first allogeneic HSCT without a previous autologous HSCT was performed in 40
      patients. 3yOS was 45%, and was significantly inferior to that in patients who
      underwent their first autologous HSCT. This result was retained after the
      correction by the different patient characteristics according to the type of
      HSCT. In conclusion, autologous HSCT is effective in prolonging survival in
      patients with relapsed and refractory HL. Allogeneic HSCT might be beneficial
      even to relapsed HL after autologous HSCT, although establishing the role of
      allogeneic HSCT remains a challenge.

PMID- 25382794
TI  - The evolving clinical management of hypertension.

PMID- 25382793
TI  - Intralesional curettage and cementation for low-grade chondrosarcoma of long
      bones: retrospective study and literature review.
AB  - BACKGROUND: Various treatment strategies for low-grade chondrosarcomas with
      variable outcomes have been reported in the literature. The aim of this study was
      to assess the oncological and functional outcomes associated with intralesional
      curettage followed by adjuvant therapy comprising high-speed burring, thermal
      cauterization, and bone cementation with polymethylmethacrylate. METHODS: We
      performed a retrospective review of 21 consecutive patients with intramedullary
      low-grade chondrosarcoma of long bones treated by intralesional curettage and
      adjuvant therapy comprising high-speed burring, thermal cauterization, and
      cementation at our institution from 2007 to 2012. RESULTS: The average age of the
      patients was 48.7 (range, 18-71) years. There were 7 male and 14 female patients.
      The mean follow-up period was 58.4 (range, 26-85) months after surgery. The
      treated lesions were located in the proximal humerus (n=10), proximal tibia
      (n=6), and distal femur (n=5). At the average follow-up time point of 58.4
      (range, 26-85) months, no patient had developed local recurrence and no distant
      metastases were observed. The average Musculoskeletal Tumor Society score among
      all 21 patients was 95% (84-100). CONCLUSIONS: The combination of intralesional
      curettage, application of high-speed burring, thermal cauterization, and
      cementation is an effective treatment strategy for low-grade intramedullary
      chondrosarcoma of long bones. Excellent oncological and functional results can be
      obtained.

PMID- 25382795
TI  - From the editors: Epilepsia's 2014 Operational Definition of Epilepsy survey.
AB  - OBJECTIVE: From March 19 to June 30, 2014, Epilepsia conducted an open access
      online survey asking directed questions related to the 2014 Operational
      Definition of Epilepsy. This study reports the findings of that poll. METHODS:
      The survey consisted of seven questions. Three questions addressed: (1) Criteria
      for when a person could be considered to have epilepsy after a single seizure;
      (2) if individuals with reflex seizures (unprovoked) have epilepsy; and (3) when
      epilepsy could be considered "resolved." Four added questions asked if responders
      were medical personal compared with patients and family members, geographic
      region of residence based on International League Against Epilepsy (ILAE)
      regions, and if responders had read the paper and if they were ILAE/International
      Bureau for Epilepsy (IBE) members. RESULTS: Of 476 that started the survey, 324
      (68%) completed it. As recommended in the ILAE report, 43% agreed that if the
      chance of a second seizure after a first one was 61-90%, then a person could be
      considered to have epilepsy. More medical professionals agreed with the 61-90%
      criteria (55%) compared with patients (21%), while more patients indicated that
      epilepsy should only be defined after two unprovoked seizures (51%) compared with
      medical professionals (21%; p < 0.0001). The majority indicated that reflex
      seizures qualify a person as having epilepsy (79%). As recommended in the ILAE
      report, 51% agreed that the definition of a person with "resolved" epilepsy would
      be 10 years seizure-free and off medication for the last 5 years. More medical
      professionals agreed with this definition (59%) compared with patients (37%),
      while more patients indicated that epilepsy is never resolved (32%) compared with
      medical professionals (7%; p < 0.0001). There were no differences based on
      geographic residence. SIGNIFICANCE: This survey found that the ILAE
      recommendations had the highest responses. However, there was clear disagreement
      with identified differences comparing medical personal with patients. These
      findings support the notion that there is a need and further opportunities for
      the ILAE to educate medical professionals and patients and their families on the
      2014 Operational Definition of Epilepsy.

PMID- 25382796
TI  - Hypercoagulability following major partial liver resection - detected by
      thrombomodulin-modified thrombin generation testing.
AB  - BACKGROUND: Conventional coagulation tests are frequently prolonged after liver
      surgery, suggesting a post-operative hypocoagulability. However, these tests are
      unreliable for assessment of the haemostatic status in these patients. In
      contrast, thrombin generation testing measures the true balance between pro- and
      anti-coagulant factors. AIM: To study the perioperative coagulation status in
      patients undergoing hemi-hepatectomy using thrombin generation assays. METHODS:
      We examined thrombin generation profiles in serial plasma samples taken from
      seventeen patients undergoing right hemi-hepatectomy. Results were compared to
      ten patients undergoing pancreatic resection and twenty-four healthy volunteers.
      In addition, we measured conventional coagulation tests and plasma levels of
      several haemostatic proteins. RESULTS: Following liver resection, the endogenous
      thrombin potential (ETP) slightly decreased until post-operative day 7. However,
      in the presence of thrombomodulin, the ETP increased [from 542 nM*min (417-694)
      at baseline to 845 nM*min (789-1050) on post-operative day 3] to values higher
      than that in healthy subjects (558 nM*min (390-680); P < 0.001), which contrasts
      with substantially prolonged PT levels. Normal to decreased thrombin generation
      was observed following pancreatic resection. Thrombin generation was only
      slightly affected by thrombomodulin after hemi-hepatectomy, while thrombin
      generation in healthy subjects decreased profoundly upon addition of
      thrombomodulin. This hypercoagulability following liver resection may be
      explained by decreased levels of protein C, S, and antithrombin and by elevated
      levels of factor VIII. CONCLUSIONS: Thrombin generation in the presence of
      thrombomodulin revealed hypercoagulability in patients following liver resection.
      These results support the recently advocated restrictive use of plasma during
      liver resection and the exploration of more extensive use of post-operative
      thrombosis prophylaxis.

PMID- 25382797
TI  - Long-term outcomes of robot-assisted radical prostatectomy: Where do we stand?

PMID- 25382798
TI  - Cytogenetic, clinical, and hematological features of pediatric myelodysplastic
      syndrome in Oman.

PMID- 25382799
TI  - Association between lichen sclerosus and celiac disease: a report of three
      pediatric cases.
AB  - The prevalence of celiac disease (CD) is increasing and may be as high as 1% of
      the US population. The typical presentation of CD generally includes
      gastrointestinal symptoms, but more individuals are presenting with
      extraintestinal manifestations. A wide variety of dermatologic associations have
      been described with CD, including alopecia, dermatitis herpetiformis, and enamel
      hypoplasia. In this report we describe three girls with CD who presented with
      hypopigmented skin lesions and pruritus in the perivaginal and perianal areas,
      consistent with the diagnosis of lichen sclerosus (LS). All three presented
      within 1 year to the same practitioner. To our knowledge, this association has
      not previously been explored in the literature. These cases elucidate a possible
      relationship between CD and LS. 

PMID- 25382800
TI  - Perennial plants for biofuel production: bridging genomics and field research.
AB  - Development of dedicated perennial crops has been indicated as a strategic action
      to meet the growing demand for biofuels. Breeding of perennial crops,however, is
      often time- and resource-consuming. As genomics offers a platform from which to
      learn more about the relationships of genes and phenotypes,its operational use in
      the context of breeding programs through strategies such as genomic selection
      promises to foster the development of perennial crops dedicated to biodiesel
      production by increasing the efficiency of breeding programs and by shortening
      the length of the breeding cycles.

PMID- 25382801
TI  - Review: clinical management of Helicobacter pylori infection in China.
AB  - Helicobacter pylori (H. pylori) infection has been associated with gastric
      disorders. The situation of H. pylori infection in China-where a high prevalence
      of H. pylori infection, a high incidence of gastric cancer, and widespread
      resistance to clarithromycin, metronidazole, and levofloxacin exist-is quite
      different from that in Western countries. In order for Chinese clinicians to
      better manage H. pylori infection, a Chinese Study Group on H. pylori published
      four consensus reports regarding the management of H. pylori infection in China
      between 1999 and 2012. The eradication rate with standard triple therapy was <80%
      in most areas of China. Bismuth is available in China, and bismuth-containing
      quadruple therapy has been shown to produce a high eradication rate; thus,
      bismuth quadruple therapy could be recommended both as an initial and as a rescue
      therapy in China. There is no advantage of sequential therapy over triple therapy
      in Chinese patients, but the efficacy of concomitant therapy must be studied
      further. This review introduces the epidemiology, diagnosis, indicators, and
      therapies for the eradication of H. pylori in China in recent years. 

PMID- 25382803
TI  - Retention of first aid and basic life support skills in undergraduate medical
      students.
AB  - BACKGROUND: Undergraduate medical students follow a compulsory first aid (FA) and
      basic life support (BLS) course. Retention of BLS seems poor and only little
      information is provided on the retention of FA skills. This study aims at
      evaluating 1- and 2-year retention of FA and BLS training in undergraduate
      medical students. METHODS: One hundred and twenty students were randomly selected
      from first year (n=349) medical students who successfully followed a compulsory
      FA and BLS course. From these 120 students, 94 (78%) and 69 (58%) participated in
      retention tests of FA and BLS skills after 1 and 2 years, respectively. The
      assessment consisted of two FA stations and one BLS station. RESULTS: After 1
      year, only 2% passed both FA and BLS stations and 68% failed both FA and BLS
      stations. After 2 years, 5% passed and 50% failed both FA and BLS stations.
      Despite the high failure rate at the stations, 90% adequately checked vital signs
      and started cardiopulmonary resuscitation appropriately. CONCLUSIONS: The long
      term retention of FA and BLS skills after a compulsory course in the first year
      is poor. Adequate check of vital signs and commencing cardiopulmonary
      resuscitation retained longer.

PMID- 25382802
TI  - The wingless-related integration site-5a/secreted frizzled-related protein-5
      system is dysregulated in human sepsis.
AB  - Sepsis and type 2 diabetes exhibit insulin resistance as a common phenotype. In
      type 2 diabetes we and others have recently provided evidence that alterations of
      the proinflammatory wingless-related integration site (wnt)-5a/anti-inflammatory
      secreted frizzled-related protein (sFRP)-5 system are involved in the
      pathogenesis of insulin resistance. The aim of the present study was to
      investigate whether this novel cytokine system is dysregulated in human sepsis,
      which may indicate a potential mechanism linking inflammation to metabolism. In
      this single-centre prospective observational study, critically ill adult septic
      patients were examined and proinflammatory wnt5a and wnt5a inhibitor sFRP5 were
      measured in serum samples by enzyme-linked immunosorbent assay (ELISA) at
      admission to the intensive care unit (ICU) and 5 days later. Sixty sepsis
      patients were included, and 30 healthy individuals served as controls. Wnt5a
      levels were found to be increased significantly in septic patients compared to
      healthy controls (2.21 +/- 0.33 versus 0.32 +/- 0.03 ng/ml, P < 0.0001). In
      contrast, sFRP5 was not altered significantly in septic patients (19.72 +/- 3.06
      versus 17.48 +/- 6.38 ng/ml, P = 0.07). On admission to the ICU, wnt5a levels
      exhibited a significant positive correlation with the leucocyte count (rs  =
      0.3797, P = 0.004). Interestingly, in patients recovering from sepsis, wnt5a
      levels declined significantly within 5 days (2.17 +/- 0.38-1.03 +/- 0.28 ng/ml, P
      < 0.01). In contrast, if sepsis was worsening, wnt5a levels increased in the same
      time-period by trend (2.34 +/- 0.59-3.25 +/- 1.02 ng/ml, P > 0.05). sFRP5 levels
      did not change significantly throughout the study period. The wnt5a/sFRP5 system
      is altered in human sepsis and might therefore be of interest for future studies
      on molecular pathophysiology of this common human disease. 

PMID- 25382804
TI  - Comparability of higher order structure in proteins: chemometric analysis of
      second-derivative amide I Fourier transform infrared spectra.
AB  - Comparing higher order structure (HOS) in therapeutic proteins is a significant
      challenge. Previously, we showed that changes in solution conditions produced
      detectable changes in the second-derivative amide I Fourier transform infrared
      (FTIR) spectra for a variety of model proteins. Those comparisons utilized vector
      based approaches, such as spectral overlap and spectral correlation coefficients
      to quantify differences between spectra. In this study, chemometric analyses of
      the same data were performed, to classify samples into different groups based on
      the solution conditions received. The solution conditions were composed of
      various combinations of temperature, pH, and salt types. At first, principal
      component analysis (PCA) was used to visually demonstrate that FTIR spectra
      respond to changes in solution conditions, which, presumably indicates variations
      in HOS. This observed when samples from the same solution condition form clusters
      within a PCA score plot. The second approach, called soft independent modeling of
      class analogy (SIMCA), was conducted to account for the within-class experimental
      error for the lysozyme spectra. The DModX values, indicative of the distance of
      each spectra to their respective class models, was found to be a more sensitive
      quantitative indicator of changes in HOS, when compared with the modified area of
      overlap algorithm. The SIMCA approach provides a metric to determine whether new
      observations do, or do not belong to a particular class or group. Thus, SIMCA is
      the recommended approach when multiple samples from each condition are available.

PMID- 25382805
TI  - Spectra Optia granulocyte apheresis collections result in higher collection
      efficiency of viable, functional neutrophils in a randomized, crossover,
      multicenter trial.
AB  - BACKGROUND: Granulocyte transfusion from healthy donors is used in the treatment
      of patients with granulocyte function defects, or transient neutropenia and
      severe bacterial or fungal infections resistant to maximal antimicrobial
      treatment. STUDY DESIGN AND METHODS: This study evaluated the performance and
      safety of the newly developed granulocyte collection protocol of the Spectra
      Optia in a prospective, multicenter, open-label, randomized, paired crossover
      trial compared with the COBE Spectra apheresis system in a population of 32
      evaluable healthy subjects. All subjects received granulocyte-colony-stimulating
      factor and dexamethasone before collection. RESULTS: Granulocyte procedures from
      Spectra Optia apheresis procedures had an approximately 23% higher
      polymorphonuclear (PMN) collection efficiency (CE) than the COBE Spectra
      collections (mean, 53.7% vs. 43.2%; p < 0.01), while the platelet CE (10.9% vs.
      10.8%, respectively) and hematocrit (7.4% vs. 7.4%) were comparable between
      collections on both devices. Spectra Optia collections generated a higher total
      PMN yield per liter of blood processed than those produced by the COBE Spectra
      (with means of 8.6 * 10(10) vs. 6.8 * 10(10) , respectively). Granulocyte
      viability was more than 99% with both devices, and chemotaxic and bacterial
      killing activities of circulating versus collected granulocytes were similarly
      preserved. Fewer operator adjustments were required with Spectra Optia and there
      was no significant difference in the number or intensity of adverse events
      between instruments. CONCLUSION: CE of the granulocyte collection procedure with
      the Spectra Optia was approximately 10 percentage points higher than with the
      COBE Spectra, required less operator involvement, and is safe for clinical
      implementation.

PMID- 25382806
TI  - Evidence for charge-trapping inducing polymorphic structural-phase transition in
      pentacene.
AB  - Trapped-charge-induced transformation of pentacene polymorphs is observed by
      using in situ Raman spectroscopy and molecular dynamics simulations reveal that
      the charge should be localized in pentacene molecules at the interface with
      static intermolecular disorder along the long axis. Quantum chemical calculations
      of the intermolecular transfer integrals suggest the disorder to be large enough
      to induce Anderson-type localization. 

PMID- 25382807
TI  - Estimation of an optimal chemotherapy utilization rate for malignant pleural
      mesothelioma: an evidence-based benchmark for cancer care.
AB  - AIMS: Chemotherapy with cisplatin and pemetrexed has been shown to provide a
      survival benefit and improvement in quality of life in patients with malignant
      pleural mesothelioma (MPM). The reported chemotherapy utilization rates range
      from 18% to 61%. This study aimed to estimate the proportion of MPM patients that
      should receive chemotherapy based on best available evidence. METHODS: An optimal
      chemotherapy utilization model for MPM was constructed using indications for
      chemotherapy identified from evidence-based MPM treatment guidelines.
      Epidemiological data on the proportion of patients and their tumor-related
      attributes were combined with the chemotherapy indications to estimate the
      optimal chemotherapy utilization rate using decision analysis software (TreeAge
      Pro 2007). Sensitivity analyses were performed to assess the impact of major
      variations in the epidemiological data on the optimal chemotherapy utilization
      rate. The optimal rate was compared with the actual rate reported in the
      literature. RESULTS: Chemotherapy is recommended at least once during the disease
      trajectory in 65% of MPM patients. Sensitivity analyses indicate an optimal
      utilization rate ranging from 50% to 65%. This optimal rate is relatively
      comparable to the rates mentioned in contemporary reports from Canada (61%
      between 2003 and 2005) and Australia (54% between 2007 and 2009) and high when
      compared with data from the Netherlands (36% during 2005-2006). CONCLUSION: An
      evidence-based model provided an optimal chemotherapy utilization rate of 65% for
      patients with MPM. Chemotherapy for MPM may be underutilized and barriers are
      likely multifactorial.

PMID- 25382808
TI  - Pallidal stimulation for acquired dystonia due to cerebral palsy: beyond 5 years.
AB  - BACKGROUND AND PURPOSE: There is increasing evidence that deep brain stimulation
      (DBS) of the globus pallidus internus (GPi) is effective in patients with
      idiopathic or inherited generalized dystonia. There is comparatively less
      experience about the effects of GPi DBS on acquired dystonia, particularly
      dystonia due to cerebral palsy (DCP). Clinical and demographic outcome predictors
      for DBS in dystonia syndromes are also poorly defined. Our aim was to examine the
      efficacy and safety of GPi DBS for the treatment of generalized DCP. METHODS:
      Fifteen patients with DCP up to 6.2 years after DBS surgery were studied. Only
      mild limb spasticity or mild static brain magnetic resonance imaging
      abnormalities were acceptable for inclusion. Dystonia severity and disability
      were assessed by the Burke-Fahn-Marsden dystonia rating scale (BFMDRS), and
      health-related quality of life was assessed by the Short Form General Health
      Survey (SF-36) scale. The amount of energy delivered was calculated, and adverse
      events and side effects were collected. RESULTS: At last follow-up, BFMDRS motor
      score improved on average by 49.5%, and the disability score improved by 30%.
      Health-related quality of life improved in most patients. Age at implant, age at
      onset and disease duration did not correlate to outcome, whilst higher pre
      operative dystonia severity and occurrence of spasticity were associated with
      poorer outcome. The patients received a stable amount of energy after the first 2
      years post-implant and throughout all the observation period. There were few
      serious adverse events or side effects. CONCLUSIONS: The outcome was encouraging
      in the majority of DCP patients, with a stable outlook and a good safety profile.

PMID- 25382810
TI  - In reference to Admission after sleep surgery is unnecessary in patients without
      cardiovascular disease.

PMID- 25382809
TI  - Stereo- and regioselective phyllobilane oxidation in leaf homogenates of the
      peace lily (Spathiphyllum wallisii): hypothetical endogenous path to yellow
      chlorophyll catabolites.
AB  - In senescent leaves, chlorophyll typically is broken down to colorless and
      essentially photo-inactive phyllobilanes, which are linear tetrapyrroles
      classified as "nonfluorescent" chlorophyll catabolites (NCCs) and dioxobilane
      type NCCs (DNCCs). In homogenates of senescent leaves of the tropical evergreen
      Spathiphyllum wallisii, when left at room temperature and extracted with
      methanol, the major endogenous, naturally formed NCC was regio- and
      stereoselectively oxidized (in part) to a mixture of its 15-hydroxy and 15
      methoxy derivative. In the absence of methanol in the extract, only the 15-OH-NCC
      was observed. The endogenous oxidation process depended upon molecular oxygen. It
      was inhibited by carbon monoxide, as well as by keeping the leaf homogenate and
      extract at low temperatures. The remarkable "oxidative activity" was inactivated
      by heating the homogenate for 10 min at 70  degrees C. Upon addition of a natural
      epimeric NCC (epiNCC) to the homogenate of senescent or green Sp. wallisii leaves
      at room temperature, the exogenous epiNCC was oxidized regio- and
      stereoselectively to 15-OH-epiNCC and 15-OMe-epiNCC. The identical two oxidized
      epiNCCs were also obtained as products of the oxidation of epiNCC with
      dicyanodichlorobenzoquinone (DDQ). Water elimination from 15-OH-epiNCC occurred
      readily and gave a known "yellow" chlorophyll catabolite (YCC). The endogenous
      oxidation process, described here, may represent the elusive natural path from
      the colorless NCCs to yellow and pink coloured phyllobilins, which were found in
      (extracts of) some senescent leaves. 

PMID- 25382811
TI  - Training in global health and international emergency medicine: Where to next?

PMID- 25382814
TI  - Computational and synthetic studies with tetravinylethylenes.
AB  - Computational and experimental studies offer fresh insights into the neglected
      tetravinylethylene class of compounds. Both the structures and the outcomes of
      exploratory reactions of the parent hydrocarbon are predicted and explained in
      detail through high-level composite ab initio MO G4(MP2) computational studies. 

PMID- 25382815
TI  - Carrier thermalization dynamics in single zincblende and wurtzite InP Nanowires.
AB  - Using transient Rayleigh scattering (TRS) measurements, we obtain photoexcited
      carrier thermalization dynamics for both zincblende (ZB) and wurtzite (WZ) InP
      single nanowires (NW) with picosecond resolution. A phenomenological fitting
      model based on direct band-to-band transition theory is developed to extract the
      electron-hole-plasma density and temperature as a function of time from TRS
      measurements of single nanowires, which have complex valence band structures. We
      find that the thermalization dynamics of hot carriers depends strongly on
      material (GaAs NW vs InP NW) and less strongly on crystal structure (ZB vs WZ).
      The thermalization dynamics of ZB and WZ InP NWs are similar. But a comparison of
      the thermalization dynamics in ZB and WZ InP NWs with ZB GaAs NWs reveals more
      than an order of magnitude slower relaxation for the InP NWs. We interpret these
      results as reflecting their distinctive phonon band structures that lead to
      different hot phonon effects. Knowledge of hot carrier thermalization dynamics is
      an essential component for effective incorporation of nanowire materials into
      electronic devices. 

PMID- 25382816
TI  - Temporary implantable nitinol device (TIND): a novel, minimally invasive
      treatment for relief of lower urinary tract symptoms (LUTS) related to benign
      prostatic hyperplasia (BPH): feasibility, safety and functional results at 1 year
      of follow-up.
AB  - OBJECTIVES: To report the first clinical experience with a temporary implantable
      nitinol device (TIND; Medi-Tate((r)) ) for the treatment of lower urinary tract
      symptoms (LUTS) due to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS:
      In all, 32 patients with LUTS were enrolled in this prospective study, which was
      approved by our Institutional Ethics Committee. Inclusion criteria were: age >50
      years, International Prostate Symptom Score (IPSS) of >=10, maximum urinary flow
      rate (Qmax ) of <=12 mL/s, and prostate volume of <60 mL. The TIND was implanted
      within the bladder neck and the prostatic urethra under light sedation, using a
      rigid cystoscope. The device was removed 5 days later in an outpatient setting.
      Demographics, perioperative results, complications (according to the Clavien
      system), functional results and quality of life (QoL) were evaluated. Follow-up
      assessments were made at 3 and 6 weeks, and 3, 6 and 12 months postoperatively.
      The Student's t-test, analysis of variance (anova), Kruskall-Wallis test, and
      simple and multiple linear regression models were used in the statistical
      analyses. RESULTS: The mean patient age was 69.4 years, the mean (standard
      deviation, sd) prostate volume was 29.5 (7.4) mL and the Qmax was 7.6 (2.2) mL/s.
      The median (interquartile range, IQR) IPSS was 19 (14-23) and QoL score was 3 (3
      4). All the implantations were successful, with no intraoperative complications
      recorded. The mean operative time (sd) was 5.8 (2.5) min and the median (IQR)
      postoperative stay was 1 (1-2) day. All but one of the devices (96%) was removed
      5 days at after implantation in an outpatient setting. Four complications (12.5%)
      were recorded, including urinary retention (one, 3.1%), transient incontinence
      due to device displacement (one, 3.1%), prostatic abscess (one, 3.1%), and
      urinary tract infection (one, 3.1%). Multiple regression analysis failed to
      identify any independent prognostic factor for complications. There were
      statistically significant differences in the IPSS, QoL score and Qmax when
      comparing pre- and postoperative results at every time point. After 12 months,
      the median (IQR) IPSS and QoL score were 9 (7-13) and 1 (1-2), respectively, and
      the mean (sd) Qmax was 12 (4.7) mL/s. The mean variations with respect to
      baseline conditions at the same time points were -45% for the IPSS and +67% for
      Qmax . At 12 months after surgery (last follow-up visit), no patients required
      medical therapy or surgical procedures for BPH. CONCLUSION: TIND implantation is
      a feasible and safe minimally invasive option for the treatment of BPH-related
      LUTS. The functional results are encouraging and the treatment significantly
      improved patient QoL. Further studies are required to assess durability of TIND
      results and to optimise the indications of such a procedure.

PMID- 25382817
TI  - Fiber consumption and all-cause, cardiovascular, and cancer mortalities: a
      systematic review and meta-analysis of cohort studies.
AB  - The present meta-analysis aimed to investigate fiber consumption and all-cause
      mortality, and cause-specific mortality. MEDLINE and web of science database were
      searched for cohort studies published from inception to August 2014. Studies were
      included if they provided a hazard ratio (HR) and corresponding 95% CI for
      mortality in relation to fiber consumption.We found that, compared with those who
      consumed lowest fiber, for individuals who ate highest fiber, mortality rate was
      lower by 23% (HR, 0.77; 95% CI, 0.72-0.81) for CVD, by 17% (HR, 0.83; 95% CI,
      0.74-0.91) for cancer, by 23% (HR, 0.77; 95% CI, 0.73-0.81) for all-cause
      mortality. For each 10 g/day increase in fiber intake, the pooled HR was
      estimated to be 0.89 (95% CI, 0.86-0.93) for all-cause mortality, 0.80 (95% CI,
      0.72-0.88) for CHD mortality, and 0.66 (95% CI, 0.40-0.92) for IHD mortality,
      0.91 (95% CI, 0.88-0.94) for cancer. Dietary fiber and CVD mortality showed a
      strong dose-response relation. Apparently, fiber consumption is inversely
      associated with all-cause mortality and CVD, IHD, cancer mortality. 

PMID- 25382820
TI  - A unique case of concurrent chronic lymphocytic leukemia/small lymphocytic
      lymphoma and lymphomatoid papulosis in the same biopsy.
AB  - Chronic lymphocytic leukemia (CLL/SLL) is the most common leukemia in the western
      world and its cutaneous dissemination a very uncommon phenomenon. Lymphomatoid
      papulosis (LyP) is a CD30+ lymphoproliferative disorder characterized by chronic,
      recurrent and self healing skin lesions. Up to 20% of patients with LyP have a
      coexistent lymphoma. While the association between the two entities has been
      reported, their coexistence has never been documented. We describe a 74-year-old
      man with known CLL and thrombocytopenia who presented with a 2 year history of
      recurrent nodules and plaques to both arms and legs that resolved within 4-6
      weeks after administration of rituximab and bendamustin for his CLL treatment.
      His biopsies showed an atypical lymphoid infiltrate, composed of large and
      pleomorphic cells with a nodular and interstitial pattern in a background of
      eosinophils. Immunohistochemical staining revealed a pattern of two separate yet
      coexisting neoplastic processes; a large CD30 positive T-cell lymphoproliferative
      disorder, while the other one was diagnostic of a neoplastic B-cell process
      (leukemia cutis). A diagnosis of coexistent LyP and cutaneous involvement by
      CLL/SLL was rendered. The simultaneous presence of both disorders can be a
      pitfall in the differential diagnosis of large cell lymphomas, such as Richter's
      transformation of CLL/SLL.

PMID- 25382818
TI  - Quality Control and Reproducibility in M-Mode, Two-Dimensional, and Speckle
      Tracking Echocardiography Acquisition and Analysis: The CARDIA Study, Year 25
      Examination Experience.
AB  - INTRODUCTION: Few large studies describe quality control procedures and
      reproducibility findings in cardiovascular ultrasound, particularly in novel
      techniques such as speckle tracking echocardiography (STE). We evaluate the
      echocardiography assessment performance in the Coronary Artery Risk Development
      in Young Adults (CARDIA) study Year 25 (Y25) examination (2010-2011) and report
      findings from a quality control and reproducibility program conducted to assess
      Field Center image acquisition and reading center (RC) accuracy. METHODS: The
      CARDIA Y25 examination had 3475 echocardiograms performed in 4 US Field Centers
      and analyzed in a RC, assessing standard echocardiography (LA dimension, aortic
      root, LV mass, LV end-diastolic volume [LVEDV], ejection fraction [LVEF]), and
      STE (two- and four-chamber longitudinal, circumferential, and radial strains).
      Reproducibility was assessed using intraclass correlation coefficients (ICC),
      coefficients of variation (CV), and Bland-Altman plots. RESULTS: For standard
      echocardiography reproducibility, LV mass and LVEDV consistently had CV above 10%
      and aortic root below 6%. Intra-sonographer aortic root and LV mass had the most
      robust values of ICC in standard echocardiography. For STE, the number of
      properly tracking segments was above 80% in short-axis and four-chamber and 58%
      in two-chamber views. Longitudinal strain parameters were the most robust and
      radial strain showed the highest variation. Comparing Field Centers with
      echocardiography RC STE readings, mean differences ranged from 0.4% to 4.1% and
      ICC from 0.37 to 0.66, with robust results for longitudinal strains. CONCLUSION:
      Echocardiography image acquisition and reading processes in the CARDIA study were
      highly reproducible, including robust results for STE analysis. Consistent
      quality control may increase the reliability of echocardiography measurements in
      large cohort studies.

PMID- 25382819
TI  - ProKinO: a unified resource for mining the cancer kinome.
AB  - Protein kinases represent a large and diverse family of evolutionarily related
      proteins that are abnormally regulated in human cancers. Although genome
      sequencing studies have revealed thousands of variants in protein kinases,
      translating "big" genomic data into biological knowledge remains a challenge.
      Here, we describe an ontological framework for integrating and conceptualizing
      diverse forms of information related to kinase activation and regulatory
      mechanisms in a machine readable, human understandable form. We demonstrate the
      utility of this framework in analyzing the cancer kinome, and in generating
      testable hypotheses for experimental studies. Through the iterative process of
      aggregate ontology querying, hypothesis generation and experimental validation,
      we identify a novel mutational hotspot in the alphaC-beta4 loop of the kinase
      domain and demonstrate the functional impact of the identified variants in
      epidermal growth factor receptor (EGFR) constitutive activity and inhibitor
      sensitivity. We provide a unified resource for the kinase and cancer community,
      ProKinO, housed at http://vulcan.cs.uga.edu/prokino.

PMID- 25382821
TI  - A minimally invasive technique for lateral maxillary sinus floor elevation: a
      Bayesian network study.
AB  - OBJECTIVES: To describe a minimally invasive technique for lateral maxillary
      sinus elevation and to identify the relationship between the involved factors.
      MATERIALS AND METHODS: This is a retrospective study on patients treated with an
      original minimally invasive technique for lateral maxillary sinus elevation in a
      private dental clinic from 2008 to 2013. Failures, complications, and
      radiographic measurements were registered 9 months after surgery at the
      provisional prosthesis delivery. The relationship between demographic and
      clinical factors was investigated using Bayesian network analyses. RESULTS: One
      hundred and twenty-four patients (147 maxillary sinuses) were treated, and 242
      implants were placed. Seven patients dropped out. A total of two implants in two
      patients failed. Perforation of the sinus membrane occurred in seven patients
      (6%). Five different complications in five patients were observed. Mean peri
      implant marginal bone level 9 months after surgery was 1.10 +/- 0.74 mm. Mean
      vertical bone gain was 7.44 +/- 1.95 mm. Perforation was more frequently observed
      in patients that did not undergo the sedation procedure. Complications (excluding
      perforation and including implant failure) were more frequent in cases where only
      bone substitutes were used. CONCLUSIONS: This technique can be considered
      noninvasive, with a low early failure and early complication rate.

PMID- 25382822
TI  - Synthesis of [2H7]indatraline.
AB  - Deuterium-labelled indatraline was synthesized in high efficiency employing a
      Friedel-Crafts alkylation of [(2)H6]benzene with (E)-3-(3,4
      dichlorophenyl)acrylic acid as a key step. The desired labelling of the final
      compound was ascertained in two ways, by incorporation of [(2)H6]benzene in the
      target molecule and additionally by deuterium transfer to the non-deuterated aryl
      moiety of the Friedel-Crafts alkylation product from [(2)H6]benzene, the latter
      thus serving as reagent and solvent.

PMID- 25382823
TI  - Commentary: Operational Definition of Epilepsy survey.

PMID- 25382824
TI  - Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease
      severity and survival of patients with chronic heart failure.
AB  - OBJECTIVES: Recent metabolomic, experimental and clinical studies have
      demonstrated that trimethylamine-N-oxide (TMAO), a microbiota-dependent
      metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor
      of coronary artery disease (CAD). This finding suggests a link between the gut
      microbiota and atherosclerosis. The potential impact of TMAO in chronic heart
      failure (HF) is unknown. We hypothesized that TMAO levels would provide
      prognostic information about adverse outcomes in chronic HF. DESIGN: Prospective,
      observational study including 155 consecutive patients with chronic HF. In
      addition, 100 patients with stable CAD without HF and 33 matched healthy
      individuals were included as controls. Plasma levels of TMAO and its precursors
      choline and betaine were measured, and associations with symptoms, aetiology and
      transplant-free survival in the patients with HF were explored. RESULTS: Plasma
      levels of TMAO (P = 0.01), choline (P < 0.001) and betaine (P < 0.001) were
      elevated in patients with chronic HF compared to control subjects, with the
      highest levels in patients with New York Heart Association (NYHA) classes III and
      IV. Furthermore, TMAO levels were highest in individuals with ischaemic HF,
      followed by those with stable CAD and nonischaemic HF. TMAO, but not choline or
      betaine, was associated with reduced transplant-free survival: approximately 50%
      of patients in the upper tertile of TMAO levels died or received a heart
      transplant during 5.2 years of follow-up (unadjusted Cox-regression: hazard ratio
      2.24, 95% confidence interval 1.28-3.92, P = 0.005). CONCLUSIONS: TMAO levels
      were elevated in patients with HF and associated with NYHA class, ischaemic
      aetiology and adverse outcomes. Future studies should focus on gut microbiota,
      dietary composition and intestinal dysfunction in relation to TMAO levels and
      clinical outcome in HF.

PMID- 25382826
TI  - Relative contributions of presystemic and systemic peptidases to oral exposure of
      a novel metabotropic glutamate 2/3 receptor agonist (LY404039) after oral
      administration of prodrug pomaglumetad methionil (LY2140023).
AB  - Pomaglumetad methionil (LY2140023) is the prodrug of a novel metabotropic
      glutamate 2/3 receptor agonist (LY404039) being investigated for the treatment of
      schizophrenia. Using accelerator mass spectrometry (AMS) and an intravenous
      (i.v.) radiolabeled tracer approach, the absolute bioavailability of the prodrug
      and the extent of its conversion to active moiety (LY404039) were estimated at
      presystemic (intestinal/first pass) and systemic sites after simultaneous oral
      and i.v. dosing in healthy subjects. The mean absolute bioavailability of prodrug
      (80 mg oral) was 0.68. On the basis of these data and a previous radiolabeled
      mass balance study in which no prodrug was recovered in feces, we concluded that
      0.32 of the dose is converted to active drug in the intestinal tract. The
      fraction of prodrug converted to active moiety was approximately 1, indicating
      complete conversion of the prodrug that reaches the systemic circulation to the
      active moiety. Prodrug (80 mg oral and 100 MUg i.v.) and active moiety (100 MUg
      i.v.) were well tolerated in healthy subjects. Thus, the absolute bioavailability
      of prodrug LY2140023 and the fraction converted presystemically and systemically
      to active moiety LY404039 were estimated simultaneously using radiolabeled tracer
      microdosing and AMS.

PMID- 25382828
TI  - Individual differences in working memory moderate the relationship between
      prosaccade latency and antisaccade error rate.
AB  - Cognitive control is required for flexible responses in changing environments and
      can be assessed by measuring antisaccade error rate. Considerable variance in
      antisaccade error rate is observed in healthy participants, which motivated the
      current study to explore the cognitive factors affecting antisaccade performance.
      Relationships exist between prosaccade latency and antisaccade error rate, with
      faster prosaccade latencies linked to more antisaccade errors. Individual
      differences in working memory also impact saccadic performance. The current study
      tested the relationships among prosaccade latency, antisaccade error rate, and
      working memory in 153 healthy participants. Correlation and multiple regression
      analyses demonstrated that prosaccade latency predicted antisaccade error rate,
      and working memory moderated this relationship. These results may help elucidate
      individual differences in cognitive control among healthy individuals. 

PMID- 25382827
TI  - The value of using feasibility models in systematic conservation planning to
      predict landholder management uptake.
AB  - Understanding the social dimensions of conservation opportunity is crucial for
      conservation planning in multiple-use landscapes. However, factors that influence
      the feasibility of implementing conservation actions, such as the history of
      landscape management, and landholders' willingness to engage are often difficult
      or time consuming to quantify and rarely incorporated into planning. We examined
      how conservation agencies could reduce costs of acquiring such data by developing
      predictive models of management feasibility parameterized with social and
      biophysical factors likely to influence landholders' decisions to engage in
      management. To test the utility of our best-supported model, we developed 4
      alternative investment scenarios based on different input data for conservation
      planning: social data only; biological data only; potential conservation
      opportunity derived from modeled feasibility that incurs no social data
      collection costs; and existing conservation opportunity derived from feasibility
      data that incurred collection costs. Using spatially explicit information on
      biodiversity values, feasibility, and management costs, we prioritized locations
      in southwest Australia to control an invasive predator that is detrimental to
      both agriculture and natural ecosystems: the red fox (Vulpes vulpes). When social
      data collection costs were moderate to high, the most cost-effective investment
      scenario resulted from a predictive model of feasibility. Combining empirical
      feasibility data with biological data was more cost-effective for prioritizing
      management when social data collection costs were low (<4% of the total budget).
      Calls for more data to inform conservation planning should take into account the
      costs and benefits of collecting and using social data to ensure that limited
      funding for conservation is spent in the most cost-efficient and effective
      manner. 

PMID- 25382825
TI  - Social competence in pediatric brain tumor survivors: application of a model from
      social neuroscience and developmental psychology.
AB  - Pediatric brain tumor (BT) survivors are at risk for psychosocial late effects
      across many domains of functioning, including neurocognitive and social. The
      literature on the social competence of pediatric BT survivors is still developing
      and future research is needed that integrates developmental and cognitive
      neuroscience research methodologies to identify predictors of survivor social
      adjustment and interventions to ameliorate problems. This review discusses the
      current literature on survivor social functioning through a model of social
      competence in childhood brain disorder and suggests future directions based on
      this model. Interventions pursuing change in survivor social adjustment should
      consider targeting social ecological factors.

PMID- 25382829
TI  - The incidence of factor VIII inhibitors in severe haemophilia A following a major
      switch from full-length to B-domain-deleted factor VIII: a prospective cohort
      comparison.
AB  - Although it has been suggested that switching of factor VIII (FVIII) products may
      increase inhibitor formation this is disputed. Half of UK patients changed rFVIII
      brands because of national contracting in 2010, presenting an opportunity to
      compare inhibitor incidence of switchers with non-switchers. Centres were
      requested to test all the patients for inhibitors prior to the switching date and
      6-monthly thereafter. Positive and negative inhibitor test data were also
      collected to analyse for testing bias. A total of 1198 patients with severe
      haemophilia A and treated with Advate, Kogenate/Helixate or Refacto AF preswitch
      were included in the analysis, of whom 516 switched to Refacto-AF and 682 did not
      switch products. Five new inhibitors were reported amongst previously treated
      patients (>50 exposure days) with a median titre at the time of detection of 1.25
      BU mL(-1) (IQR 0.7-23.05). One inhibitor occurred in a non-switcher using
      Kogenate, an incidence of 1.5 per 1000 treatment-years (95% CI 0.2-10.5). Four
      inhibitors arose in patients who had switched from Kogenate (two) or Advate (two)
      to ReFacto-AF, an incidence of 7.8 per 1000 treatment-years (95% CI 2.9-20.8).
      These incidence rates did not differ significantly from one another (incidence
      rate ratio 5.3 (95% CI 0.5-260.3) or from the historical rate of 6.05
      inhibitors/1000 treatment-years (95% CI 5.18-7.06). Only one inhibitor (non
      switcher) persisted. Non-switchers were significantly older (P = 0.03), and used
      significantly less FVIII per year (P = 0.005) prior to switching. Following
      switching, factor usage increased similarly (P = 0.53) in both groups. Switching
      from FLRFVIII to Refacto-AF (BDDRFVIII) was not associated with an increased
      inhibitor development. 

PMID- 25382830
TI  - Session 1 joint opening session.

PMID- 25382831
TI  - Theme 1 improving diagnosis, prognosis and disease progression.

PMID- 25382832
TI  - Theme 2 imaging, electrophysiology and markers of disease progression.

PMID- 25382833
TI  - Theme 3 cognitive and psychological assessment and support.

PMID- 25382834
TI  - Theme 4 respiratory and nutritional management.

PMID- 25382836
TI  - Theme 6 epidemiology.

PMID- 25382835
TI  - Theme 5 multidisciplinary care and quality of life.

PMID- 25382837
TI  - Theme 7 genetics.

PMID- 25382838
TI  - Theme 8 human cell biology and pathology.

PMID- 25382839
TI  - Theme 9 in vitro experimental models.

PMID- 25382840
TI  - Theme 10 in vivo experimental models.

PMID- 25382841
TI  - Theme 11 therapeutic strategies.

PMID- 25382844
TI  - Joint opening and closing plenary sessions reflect on the continued need for new
      treatments and the hurdles that must be overcome in order for a drug to reach
      clinical trials. Introduction.

PMID- 25382845
TI  - BodyWise: evaluating a pilot body image group for patients with anorexia nervosa.
AB  - Body image disturbance can be enduring and distressing to individuals with eating
      disorders and effective treatments remain limited. This pilot study evaluated a
      group-based treatment-BodyWise-developed for use in full and partial
      hospitalization with patients with anorexia nervosa at low weight. A partial
      crossover waitlist design was used. BodyWise (N = 50) versus treatment as usual
      (N = 40) were compared on standardized measures of body image disturbance.
      Results demonstrated significant improvement in the group compared to treatment
      as usual for the primary outcome measure (Eating Disorder Examination
      Questionnaire Shape Concern subscale) and other manifestations of body image
      disturbance including body checking and body image quality of life. BodyWise
      appeared acceptable to participants, and was easy to deliver within the
      pragmatics of a busy eating disorder service. There is potential for its wider
      dissemination as a precursor to more active body image interventions.

PMID- 25382847
TI  - Commentary: Operational Definition of Epilepsy survey.

PMID- 25382846
TI  - Constitutive STAT3 activation in epidermal keratinocytes enhances cell
      clonogenicity and favours spontaneous immortalization by opposing differentiation
      and senescence checkpoints.
AB  - STAT3, a pleiotropic transcription factor acting downstream of cytokines and
      growth factors, is known to enhance proliferation, migration, invasion and
      aerobic glycolysis in tumors upon aberrant activation. In the murine epidermis,
      STAT3 is necessary for experimentally induced carcinogenesis. Skin tumorigenesis
      is conversely enhanced by overexpression in keratinocytes of the constitutively
      active STAT3C mutant, which also induces robust, psoriasis-like epidermal
      hyperplasia. We show here that STAT3C expression at physiological levels in knock
      in mice leads to mild epidermal hyperplasia and attenuated expression of terminal
      differentiation markers. Altered differentiation is confirmed in isolated primary
      epidermal keratinocytes in vitro, correlating with enhanced proliferative and
      clonogenic potential, attenuated senescence and, strikingly, high-frequency
      spontaneous immortalization. These results suggest that moderate levels of
      continuous STAT3 activation, which closely resemble those triggered by chronic
      inflammation or persistent growth factor stimulation, may establish a
      preneoplastic state in part by promoting the escape of epidermal progenitor cells
      from differentiation and senescence checkpoints. 

PMID- 25382848
TI  - Surface effects on the crystallization of ritonavir glass.
AB  - In our previous study, initiation time of crystallization was shown to be
      basically expressed as a function of only the reduced temperature, which was a
      ratio of storage and glass transition temperatures. This conclusion was obtained
      using quenched glasses with minimized surface area stored under a dried
      atmosphere. In this study, the surface effects on the crystallization were
      investigated using freeze-dried ritonavir (RTV) glass. Although quenched RTV
      glass exhibited exceptionally long initiation time, the initiation was
      accelerated by using the freeze-dried glasses. Storage of the samples under humid
      conditions further accelerated the crystallization. These surface effects
      eliminated the energetic barrier for nucleation, and the RTV glass exhibited
      universal initiation time. In contrast, subsequent crystal growth was slower for
      the freeze-dried glasses relative to the quenched one, presumably because of less
      condensed and porous structures that would suppress molecular cooperativity.
      Storage under a humid atmosphere also appeared to inhibit the crystal growth,
      presumably because of disruption of the molecular network by water. These
      findings support the existence of the universal initiation time for
      crystallization and indicated the importance of surface effects in
      crystallization behavior. Also, the suppression of crystal growth because of the
      void structure and incorporation of water molecules were indicated.

PMID- 25382849
TI  - A case-control study assessing bone mineral density in severe haemophilia A in
      the UK.
AB  - It has been shown that bone mineral density (BMD) may be lower in patients with
      haemophilia (PWH). A comparison to control subjects is required to thoroughly
      assess current BMD in PWH in the UK. The objective of this study was to test the
      hypothesis that BMD is lower in PWH than in controls, and in patients with more
      severely affected joints or lower activity levels. In this case-control study, 37
      patients with severe haemophilia A were recruited from two haemophilia centres in
      the UK. A group of 37 age, gender and ethnicity-matched control participants were
      recruited. All participants had a bone density scan, a musculoskeletal
      assessment, a blood test for vitamin D and completed a functional activity
      questionnaire. Of the case group, 5% had osteoporosis and 24% had BMD lower than
      expected for age. No control participants had osteoporosis, 3% had osteopenia and
      14% had BMD lower than expected for age. Ninety one per cent of case participants
      and 92% of control participants had reduced 25(OH)D levels. Case participants had
      significantly lower BMD than control participants, and case participants with
      more severely affected joints, lower activity levels, HIV, history of hepatitis C
      or lower BMI had significantly lower BMD. Patients with severe haemophilia have a
      higher risk of low BMD than men without haemophilia. Patients with more severely
      affected joints and lower activity levels have lower BMD. It remains unclear
      whether patients with low BMD reached adequate peak bone mass. Low vitamin D may
      be present in the majority of PWH. 

PMID- 25382852
TI  - A photostable near-infrared fluorescent tracker with pH-independent specificity
      to lysosomes for long time and multicolor imaging.
AB  - A new boron-dipyrromethene-based lysosome tracker, Lyso-NIR, is facilely
      synthesized. Besides the intensive near-infrared (NIR) fluorescence and high
      photostability, Lyso-NIR shows the capability to stably localize in lysosomes,
      which is independent of the local pH. Lyso-NIR does not have the problematic
      alkalization effect suffered by the commonly used lysotrackers; thus, it shows
      ignorable cytotoxicity and slightly affects normal physiological functions of
      lysosomes. The above advantages of Lyso-NIR make it feasible to track lysosomes'
      dynamic changes in a relatively long time during the full cellular processes such
      as apoptosis, heavy metal stimulation, and endocytosis, as is demonstrated in
      this work. Moreover, Lyso-NIR's narrow NIR emission at 740 nm with a full width
      at half-maximum smaller than 50 nm makes it easy to avoid the crosstalk with the
      emissions from other common fluorescent probes, which strengthens Lyso-NIR's
      competitiveness as a standard lysosome tracker for multicolor bioimaging.

PMID- 25382851
TI  - Biocompatible flavone-based fluorogenic probes for quick wash-free mitochondrial
      imaging in living cells.
AB  - Mitochondria, vital organelles existing in almost all eukaryotic cells, play a
      crucial role in energy metabolism and apoptosis of aerobic organisms. In this
      work, we report two new flavone-based fluorescent probes, MC-Mito1 and MC-Mito2,
      for monitoring mitochondria in living cells. These two probes exhibit remarkably
      low toxicity, good cell permeability, and high specificity; these probes
      complement the existing library of mitochondrial imaging agents. The new dyes
      give nearly no background fluorescence, and their application does not require
      tedious postwashing after cell staining. The appreciable tolerance of MC-Mito2
      encourages a broader range of biological applications for understanding the cell
      degeneration and apoptosis mechanism. 

PMID- 25382853
TI  - Design of a sorbent to enhance reactive adsorption of hydrogen sulfide.
AB  - A series of novel zinc oxide-silica composites with three-dimensionally ordered
      macropores (3DOM) structure were synthesized via colloidal crystal template
      method and used as sorbents for hydrogen sulfide (H2S) removal at room
      temperature for the first time. The performances of the prepared sorbents were
      evaluated by dynamic breakthrough testing. The materials were characterized
      before and after adsorption using scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction
      (XRD), Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron
      spectroscopy (XPS). It was found that the composite with 3DOM structure exhibited
      remarkable desulfurization performance at room temperature and the enhancement of
      reactive adsorption of hydrogen sulfide was attributed to the unique structure
      features of 3DOM composites; high surface areas, nanocrystalline ZnO and the well
      ordered interconnected macroporous with abundant mesopores. The introduction of
      silica could be conducive to support the 3DOM structure and the high dispersion
      of zinc oxide. Moisture in the H2S stream plays a crucial role in the removal
      process. The effects of Zn/Si ratio and the calcination temperature of 3DOM
      composites on H2S removal were studied. It demonstrated that the highest content
      of ZnO could reach up to 73 wt % and the optimum calcination temperature was 500 
      degrees C. The multiple adsorption/regeneration cycles showed that the 3DOM ZnO
      SiO2 sorbent is stable and the sulfur capacity can still reach 67.4% of that of
      the fresh sorbent at the fifth cycle. These results indicate that 3DOM ZnO-SiO2
      composites will be a promising sorbent for H2S removal at room temperature. 

PMID- 25382854
TI  - Growth of large-scale and thickness-modulated MoS2 nanosheets.
AB  - Two-dimensional MoS2 is a promising material for next-generation electronic and
      optoelectronic devices due to its unique electrical and optical properties
      including the band gap modulation with film thickness. Although MoS2 has shown
      excellent properties, wafer-scale production with layer control from single to
      few layers has yet to be demonstrated. The present study explored the large-scale
      and thickness-modulated growth of atomically thin MoS2 on Si/SiO2 substrates
      using a two-step sputtering-CVD method. Our process exhibited wafer-scale
      fabrication and successful thickness modulation of MoS2 layers from monolayer
      (0.72 nm) to multilayer (12.69 nm) with high uniformity. Electrical measurements
      on MoS2 field effect transistors (FETs) revealed a p-type semiconductor behavior
      with much higher field effect mobility and current on/off ratio as compared to
      previously reported CVD grown MoS2-FETs and amorphous silicon (a-Si) thin film
      transistors. Our results show that sputter-CVD is a viable method to synthesize
      large-area, high-quality, and layer-controlled MoS2 that can be adapted in
      conventional Si-based microfabrication technology and future flexible, high
      temperature, and radiation hard electronics/optoelectronics. 

PMID- 25382855
TI  - Nanometer smooth, macroscopic spherical cellulose probes for contact adhesion
      measurements.
AB  - Cellulose spheres were prepared by dissolving cellulose fibers and subsequently
      solidifying the solution in a nonsolvent. Three different solution concentrations
      were tested and several nonsolvents were evaluated for their effect on the
      formation of spheres. Conditions were highlighted to create cellulose spheres
      with a diameter of ~1 mm and a root-mean-square surface roughness of ~1 nm. These
      solid spheres were shown to be easily chemically modified without changing the
      mechanical properties significantly. Contact adhesion measurements were then
      implemented with these spheres against a poly(dimethylsiloxane) (PDMS) elastomer
      in order to quantify the adhesion. Using Johnson-Kendall-Roberts (JKR) theory, we
      quantified the adhesion for unmodified cellulose and hydrophobic cellulose
      spheres. We highlight the ability of these spheres to report more accurate
      adhesion information, compared to spin-coated thin films. The application of
      these new cellulose probes also opens up new possibilities for direct, accurate
      measurement of adhesion between cellulose and other materials instead of using
      uncertain surface energy determinations to calculate the theoretical work of
      adhesion between cellulose and different solid materials.

PMID- 25382856
TI  - Development of sol-gel icephobic coatings: effect of surface roughness and
      surface energy.
AB  - Sol-gel coatings with different roughness and surface energy were prepared on
      glass substrates. Methyl triethoxysilane (MTEOS), 3-Glycidyloxypropyl
      trimethoxysilane (GLYMO) and fluoroalkylsilane (FAS) were used to obtain a
      mechanically robust icephobic coating. Different amount of hydrophobic silica
      nano particles was added as fillers to introduce different roughness and surface
      energy to the coatings. The microstructure, roughness, and surface energy,
      together with elemental information and surface chemical state, were investigated
      at room temperature. The contact angle and sliding angle were measured at
      different temperatures to correlate the wetting behavior at low temperature with
      the anti-icing performance. The ice adhesion shear strength was measured inside
      an ice chamber using a self-designed tester. The factors influencing the ice
      adhesion were discussed, and the optimum anti-icing performance found in the
      series of coatings. It was found that lower surface energy leads to lower ice
      adhesion regardless of the roughness, while the roughness plays a more
      complicated role. The wetting behavior of the droplet on surface changes as
      temperature decreases. The anti-icing performance is closely related to the
      antiwetting property of the surfaces at subzero temperatures. 

PMID- 25382857
TI  - Effect of crystallization of Cu2ZnSnSxSe4-x counter electrode on the performance
      for efficient dye-sensitized solar cells.
AB  - Cu2ZnSnSxSe4-x (CZTSSe) counter electrodes (CEs) in dye-sensitized solar cells
      (DSSCs) are commonly developed with porous structures, but their high surface
      area could also retard electron transport processes owing to the abundant grain
      boundaries. Herein, we employed a convenient solution method and a rapid heating
      process to prepare well crystalline CZTSSe CEs in DSSCs. The influence of
      crystallization of CZTSSe film on DSSCs performances was discussed in depth. The
      thermogravimetric analysis, phase morphology, conductivity, and electrochemical
      characteristics of CZTSSe films were performed. It is found that the rapid
      heating process is beneficial to the formation of well crystalline film with
      large grains. As the porosity and grain boundaries in the bulk film are
      dramatically reduced with the enhanced crystallization, the charge transport
      process is gradually improved. Using cyclic voltammogram and electrochemical
      impedance spectroscopy measurements, we propose that the accelerating charge
      transport is of great importance to the photovoltaic performances of DSSCs due to
      their superior electrocatalytic activities. As the highest cell efficiency was
      achieved, well crystalline CZTSSe is an efficient CE catalytic material. 

PMID- 25382859
TI  - Application of PAMAM dendrimers in optical sensing.
AB  - The need for an improved sensor performance is always encouraging us towards
      exploring new materials. Following the invention of dendrimers, the possibility
      was recognised of using them for improving optical sensor performance. Their more
      important aspects are their two main structural properties: three-dimensional
      structure and multiple terminal functional groups. In this review, firstly a
      brief introduction to dendrimers is provided with the focus on PAMAM dendrimers
      and optical sensors. Recent advances have been reported in those PAMAM dendrimer
      based optical sensors, which are used for the detection of pH, cations, and other
      analyte. 

PMID- 25382858
TI  - Peptide-based, two-fluorophore, ratiometric probe for quantifying mobile zinc in
      biological solutions.
AB  - Small-molecule fluorescent sensors are versatile agents for detecting mobile zinc
      in biology. Capitalizing on the abundance of validated mobile zinc probes, we
      devised a strategy for repurposing existing intensity-based sensors for
      quantitative applications. Using solid-phase peptide synthesis, we conjugated a
      zinc-sensitive Zinpyr-1 derivative and a zinc-insensitive 7-hydroxycoumarin
      derivative onto opposite ends of a rigid P9K peptide scaffold to create HcZ9, a
      ratiometric fluorescent probe for mobile zinc. A plate reader-based assay using
      HcZ9 was developed, the accuracy of which is comparable to that of atomic
      absorption spectroscopy. We investigated zinc accumulation in prostatic cells and
      zinc levels in human seminal fluid. When normal and tumorigenic cells are bathed
      in zinc-enriched media, cellular mobile zinc is buffered and changes slightly,
      but total zinc levels increase significantly. Quantification of mobile and total
      zinc levels in human seminal plasma revealed that the two are positively
      correlated with a Pearson's coefficient of 0.73. 

PMID- 25382860
TI  - Baseline correction using asymmetrically reweighted penalized least squares
      smoothing.
AB  - Baseline correction methods based on penalized least squares are successfully
      applied to various spectral analyses. The methods change the weights iteratively
      by estimating a baseline. If a signal is below a previously fitted baseline,
      large weight is given. On the other hand, no weight or small weight is given when
      a signal is above a fitted baseline as it could be assumed to be a part of the
      peak. As noise is distributed above the baseline as well as below the baseline,
      however, it is desirable to give the same or similar weights in either case. For
      the purpose, we propose a new weighting scheme based on the generalized logistic
      function. The proposed method estimates the noise level iteratively and adjusts
      the weights correspondingly. According to the experimental results with simulated
      spectra and measured Raman spectra, the proposed method outperforms the existing
      methods for baseline correction and peak height estimation. 

PMID- 25382861
TI  - SOCIAL STRATIFICATION IN MEXICO: DISENTANGLING COLOR, ETHNICITY, AND CLASS.

PMID- 25382862
TI  - Revisiting "What They Think": Adolescent Drinking and the Importance of Peer
      Beliefs.
AB  - The association between delinquent peers and delinquent behavior is among the
      most consistent findings in the criminological literature, and a number of recent
      studies have raised the standards for determining the nature and extent of peer
      influence. Despite these advances, however, key questions about how deviant
      behavior is socially transmitted remain unresolved. In particular, much of the
      research examining peer influence is limited to peer behavior, despite a rich
      literature supporting the salience of beliefs, such as expectations and moral
      approval, in shaping behaviors. The current study takes advantage of advances in
      the modeling of peer influence and selection processes to re-examine the
      contributions of peer beliefs and behaviors to adolescent drinking. I employ
      longitudinal social network analysis to examine how peers contribute to the
      complex interplay between deviant beliefs and behaviors. I find evidence that
      beliefs related to peer drinking have both a direct and indirect impact on
      behavior and also play an important role in the friendship selection process.
      These results highlight the importance of understanding how peers influence
      deviant behavior and suggest that peer beliefs are an important part of this
      relationship.

PMID- 25382863
TI  - ESTIMATING BACTERIAL DIVERSITY IN SCIRTOTHRIPS DORSALIS (THYSANOPTERA: THRIPIDAE)
      VIA NEXT GENERATION SEQUENCING.
AB  - The last 2 decades have produced a better understanding of insect-microbial
      associations and yielded some important opportunities for insect control.
      However, most of our knowledge comes from model systems. Thrips (Thysanoptera:
      Thripidae) have been understudied despite their global importance as invasive
      species, plant pests and disease vectors. Using a culture and primer independent
      next-generation sequencing and metagenomics pipeline, we surveyed the bacteria of
      the globally important pest, Scirtothrips dorsalis Hood. The most abundant
      bacterial phyla identified were Actinobacteria and Proteobacteria and the most
      abundant genera were Propionibacterium, Stenotrophomonas, and Pseudomonas. A
      total of 189 genera of bacteria were identified. The absence of any vertically
      transferred symbiont taxa commonly found in insects is consistent with other
      studies suggesting that thrips primarilly acquire resident microbes from their
      environment. This does not preclude a possible beneficial/intimate association
      between S. dorsalis and the dominant taxa identified and future work should
      determine the nature of these associations.

PMID- 25382864
TI  - Inverted Linear Halbach Array for Separation of Magnetic Nanoparticles.
AB  - A linear array of Nd-Fe-B magnets has been designed and constructed in an
      inverted Halbach configuration for use in separating magnetic nanoparticles. The
      array provides a large region of relatively low magnetic field, yet high magnetic
      field gradient in agreement with finite element modeling calculations. The magnet
      assembly has been combined with a flow channel for magnetic nanoparticle
      suspensions, such that for an appropriate distance away from the assembly,
      nanoparticles of higher moment aggregate and accumulate against the channel wall,
      with lower moment nanoparticles flowing unaffected. The device is demonstrated
      for iron oxide nanoparticles with diameters of ~ 5 and 20 nm. In comparison to
      other approaches, the inverted Halbach array is more amenable to modeling and to
      scaling up to preparative quantities of particles.

PMID- 25382866
TI  - Take Me "Home": Return Migration among Germany's Older Immigrants.
AB  - This paper examines the determinants of return migration as foreign-born men
      approach old age in Germany. Return migration in later life engages a different
      set of conditions than return migration earlier on, including the framing of
      return as a possible retirement strategy. Using 23 years of longitudinal data
      from the German Socioeconomic Panel, this paper investigates how social and
      economic resources of immigrant men influence decisions to return "home." Results
      suggest that immigrants from former guest worker recruitment countries within the
      European Union are more likely to return than non-E.U. immigrants. In addition,
      return migrants are "negatively selected" such that those with the least
      education and weakest attachments to the labor force are more likely to emigrate.
      However, findings vary greatly depending on the immigrant's age and country of
      origin. Results from this paper highlight the heterogeneity of older immigrants
      and the factors that motivate their return "home."

PMID- 25382865
TI  - Continuous-Time System Identification of a Smoking Cessation Intervention.
AB  - Cigarette smoking is a major global public health issue and the leading cause of
      preventable death in the United States. Toward a goal of designing better smoking
      cessation treatments, system identification techniques are applied to
      intervention data to describe smoking cessation as a process of behavior change.
      System identification problems that draw from two modeling paradigms in
      quantitative psychology (statistical mediation and self-regulation) are
      considered, consisting of a series of continuous-time estimation problems. A
      continuous-time dynamic modeling approach is employed to describe the response of
      craving and smoking rates during a quit attempt, as captured in data from a
      smoking cessation clinical trial. The use of continuous-time models provide
      benefits of parsimony, ease of interpretation, and the opportunity to work with
      uneven or missing data.

PMID- 25382867
TI  - Deposition of Particles in the Alveolar Airways: Inhalation and Breath-Hold with
      Pharmaceutical Aerosols.
AB  - Previous studies have demonstrated that factors such as airway wall motion,
      inhalation waveform, and geometric complexity influence the deposition of
      aerosols in the alveolar airways. However, deposition fraction correlations are
      not available that account for these factors in determining alveolar deposition.
      The objective of this study was to generate a new space-filling model of the
      pulmonary acinus region and implement this model to develop correlations of
      aerosol deposition that can be used to predict the alveolar dose of inhaled
      pharmaceutical products. A series of acinar models was constructed containing
      different numbers of alveolar duct generations based on space-filling 14-hedron
      elements. Selected ventilation waveforms were quick-and-deep and slow-and-deep
      inhalation consistent with the use of most pharmaceutical aerosol inhalers.
      Computational fluid dynamics simulations were used to predict aerosol transport
      and deposition in the series of acinar models across various orientations with
      gravity where ventilation was driven by wall motion. Primary findings indicated
      that increasing the number of alveolar duct generations beyond 3 had a negligible
      impact on total acinar deposition, and total acinar deposition was not affected
      by gravity orientation angle. A characteristic model containing three alveolar
      duct generations (D3) was then used to develop correlations of aerosol deposition
      in the alveolar airways as a function of particle size and particle residence
      time in the geometry. An alveolar deposition parameter was determined in which
      deposition correlated with d2t over the first half of inhalation followed by
      correlation with dt2, where d is the aerodynamic diameter of the particles and t
      is the potential particle residence time in the alveolar model. Optimal breath
      hold times to allow 95% deposition of inhaled 1, 2, and 3 MUm particles once
      inside the alveolar region were approximately >10, 2.7, and 1.2 s, respectively.
      Coupling of the deposition correlations with previous stochastic individual path
      (SIP) model predictions of tracheobronchial deposition was demonstrated to
      predict alveolar dose of commercial pharmaceutical products. In conclusion, this
      study completes an initiative to determine the fate of inhaled pharmaceutical
      aerosols throughout the respiratory airways using CFD simulations.

PMID- 25382868
TI  - Bioactive Agarose Carbon-Nanotube Composites are Capable of Manipulating Brain
      Implant Interface.
AB  - Composite electrodes made of the polysaccharide agarose and carbon nanotube
      fibers (A-CNE) have shown potential to be applied as tissue-compatible, micro
      electronic devices. In the present work, A-CNEs were functionalized using neuro
      relevant proteins (laminin and alpha-melanocyte stimulating hormone) and
      implanted in brain tissue for 1 week (acute response) and 4 weeks (chronic
      response). Qualitative and quantitative analysis of neuronal and immunological
      responses revealed significant changes in immunological response to implanted
      materials depending on the type of biomolecule used. The potential to manipulate
      tissue response through the use of an anti-inflammatory protein, alpha-melanocyte
      stimulating hormone, was shown in the reduction of astroglia presence near the
      implant site during the glial scar formation. These results suggest that A-CNEs,
      which are soft, flexible, and easily made bioactive, have the ability to modify
      brain tissue response through surface modification as a function of the
      biomolecule used.

PMID- 25382869
TI  - Synthesis and Characterization of Surface Grafted Poly(N-isopropylacrylamide) and
      Poly(Carboxylic Acid)- Iron Particles via Atom Transfer Radical Polymerization
      for Biomedical Applications.
AB  - This research relates to the preparation and characterization of surface grafted
      poly(N-isopropylacrylamide) and poly(carboxylic acid)-micron-size iron particles
      via atom transfer radical polymerization (ATRP). The surface grafted polymers
      iron particles result in multifunctional materials which can be used in
      biomedical applications. The functionalities consist of cell targeting, imaging,
      drug delivery, and immunological response. The multifunctional materials are
      synthesized in two steps. First, surface grafting is used to place polymer
      molecules on the iron particles surface. The second step, is conjugation of the
      bio-molecules onto the polymer backbone. Fourier transform infrared (FTIR)
      spectroscopy and scanning electron microscopy were used to confirm the presence
      of polymers on the iron particles. The thickness of the grafted polymers and
      glass transition temperature of the surface grafted polymers were determined by
      transmission electron microscopy (TEM) and differential scanning calorimetry
      (DSC). The covalent bond between grafted polymers and iron particles caused
      higher glass transition temperature as compared with non-grafted polymers. The
      ability to target the bio-molecule and provide fluorescent imaging was simulated
      by conjugation of rat immunoglobulin and fluorescein isothiocyanate (FITC)
      labeled anti-rat. The fluorescence intensity was determined using flow cytometry
      and conjugated IgG-FITC anti-rat on iron particles which was imaged using a
      fluorescence microscopy.

PMID- 25382870
TI  - THE LANGUAGE OF BLACK GAY MEN'S SEXUAL BEHAVIOR: IMPLICATIONS FOR AIDS RISK
      REDUCTION.
AB  - The development of appropriate AIDS risk reduction interventions targeted at
      African-American gay men could be aided by an awareness of their terminology for
      specific sexual behaviors and types of sexual encounters. This paper explores
      similarities and differences between the HIV-related sexual language of Black and
      White gay men. While much of the vernacular is shared, differences in some terms
      and greater or lesser emphasis on others are apparent.

PMID- 25382871
TI  - Silica Nanowires: Growth, Integration, and Sensing Applications.
AB  - This review (with 129 refs.) gives an overview on how the integration of silica
      nanowires (NWs) into micro-scale devices has resulted, in recent years, in simple
      yet robust nano-instrumentation with improved performance in targeted application
      areas such as sensing. This has been achieved by the use of appropriate
      techniques such as di-electrophoresis and direct vapor-liquid-growth phenomena,
      to restrict the growth of NWs to site-specific locations. This also has
      eliminated the need for post-growth processing and enables nanostructures to be
      placed on pre-patterned substrates. Various kinds of NWs have been investigated
      to determine how their physical and chemical properties can be tuned for
      integration into sensing structures. NWs integrated onto interdigitated micro
      electrodes have been applied to the determination of gases and biomarkers. The
      technique of directly growing NWs eliminates the need for their physical transfer
      and thus preserves their structure and performance, and further reduces the costs
      of fabrication. The biocompatibility of NWs also has been studied with respect to
      possible biological applications. This review addresses the challenges in growth
      and integration of NWs to understand related mechanism on biological contact or
      gas exposure and sensing performance for personalized health and environmental
      monitoring.

PMID- 25382873
TI  - Inverse Optimization: A New Perspective on the Black-Litterman Model.
AB  - The Black-Litterman (BL) model is a widely used asset allocation model in the
      financial industry. In this paper, we provide a new perspective. The key insight
      is to replace the statistical framework in the original approach with ideas from
      inverse optimization. This insight allows us to significantly expand the scope
      and applicability of the BL model. We provide a richer formulation that, unlike
      the original model, is flexible enough to incorporate investor information on
      volatility and market dynamics. Equally importantly, our approach allows us to
      move beyond the traditional mean-variance paradigm of the original model and
      construct "BL"-type estimators for more general notions of risk such as coherent
      risk measures. Computationally, we introduce and study two new "BL"-type
      estimators and their corresponding portfolios: a Mean Variance Inverse
      Optimization (MV-IO) portfolio and a Robust Mean Variance Inverse Optimization
      (RMV-IO) portfolio. These two approaches are motivated by ideas from arbitrage
      pricing theory and volatility uncertainty. Using numerical simulation and
      historical backtesting, we show that both methods often demonstrate a better risk
      reward tradeoff than their BL counterparts and are more robust to incorrect
      investor views.

PMID- 25382872
TI  - Regulation of Myf5 Early Enhancer by Histone Acetyltransferase p300 during Stem
      Cell Differentiation.
AB  - Skeletal myogenesis is an intricate process coordinated temporally by multiple
      myogenic regulatory factors (MRF) including Myf5, which is the first MRF
      expressed and marks the commitment of skeletal muscle lineage. The expression of
      Myf5 gene during early embryogenesis is controlled by a set of enhancer elements,
      and requires the histone acetyltransferase (HAT) activity of transcriptional
      coactivator p300. However, it is unclear as to how different regulatory signals
      converge at enhancer elements to regulate early Myf5 gene expression, and if p300
      is directly involved. We show here that p300 associates with the Myf5 early
      enhancer at the early stage of stem cell differentiation, and its HAT activity is
      important for the recruitment of beta-catenin to this early enhancer. In
      addition, histone H3-K27 acetylation, but not H3-K9/14, is intimately connected
      to the p300 HAT activity. Thus, p300 is directly involved in the regulation of
      the Myf5 early enhancer, and is important for specific histone acetylation and
      transcription factor recruitment. This connection of p300 HAT activity with H3
      K27 acetylation and beta-catenin signalling during myogenic differentiation in
      vitro offers a molecular insight into the enhancer-elements participation
      observed in embryonic development. In addition, pluripotent stem cell
      differentiation is a valuable system to dissect the signal-dependent regulation
      of specific enhancer element during cell fate determinations.

PMID- 25382875
TI  - Region-Urbanicity Differences in Locus of Control: Social Disadvantage,
      Structure, or Cultural Exceptionalism?
AB  - People with internal rather than external locus of control experience better
      outcomes in multiple domains. Previous studies on spatial differences in control
      within America only focused on the South, relied on aggregate level data or
      historical evidence, or did not account for other confounding regional
      distinctions (such as variation in urbanicity). Using data from the National
      Education Longitudinal Study, we find differences in adolescents' loci of control
      depending on their region and urbanicity are largely attributable to differences
      in their social background, and only minimally to structural differences (i.e.,
      differences in the qualities of adolescents' schools). Differences that persist
      net of differences across adolescents and their schools suggest the less internal
      control of rural Southern adolescents, and the more internal control of rural and
      urban Northeastern adolescents, may be due to cultural distinctions in those
      areas. Results indicate region is more closely associated than urbanicity with
      differences in locus of control, with Western and Northeastern cultures seemingly
      fostering more internal control than Midwestern and Southern cultures. These
      findings contribute to research on spatial variation in a variety of
      psychological traits.

PMID- 25382876
TI  - Synthesis of Hydrophilic Aminooxy Linkers and Multivalent Cores for
      Chemoselective Aldehyde/Ketone Conjugation.
AB  - A series of three linear and two trivalent aminooxy-containing hydrophilic
      linkers and cores were synthesized. The five molecules contain from one to three
      aminooxy groups, and all but one contain an ether for enhanced aqueous
      solubility. These unique and versatile molecules can be utilized in the
      chemoselective conjugation of aldehyde/ketone-containing molecules, including
      reducing sugars, under mild aqueous conditions, and give rise to oxime-containing
      conjugates useful in a wide variety of applications and studies. The value of
      these aminooxy-based molecules and the ease and speed of preparation of both
      monovalent and multivalent oxime-linked molecules is demonstrated in two examples
      using the disaccharide cellobiose; one with a linear linker, and the second with
      a trivalent core.

PMID- 25382877
TI  - Decomposing Racial Disparities in Prison and Drug Treatment Commitments for
      Criminal Offenders in California.
AB  - Blacks convicted of drug-related offenses in the U.S. have higher prison
      commitment rates than Whites. Studies have been largely unsuccessful in
      explaining these disparities. This study uses administrative data from a random
      sample of individuals arrested for drug offenses in California to examine this
      issue. We use a decomposition model to estimate whether Black-White disparities
      in commitments to prison or diversions to drug treatment are attributable to
      differences in the characteristics of criminal cases and whether case
      characteristics are weighed differently by race. We also examine whether the
      influence of case characteristics changes after California implemented
      Proposition 36, which was a mandatory prison diversion program for eligible drug
      offenders. Our results suggest that Black-White differences in prison commitments
      are fully explained by criminal case characteristics, but that a significant
      portion of the differences in treatment diversions remain unexplained. The
      unexplained variation in drug treatment also does not change after Proposition
      36. These findings suggest that case characteristics play a larger role in
      explaining prison commitments for drug offenders than the discretion of
      prosecutors and judges. By contrast, diversion to drug treatment appears to be
      driven more by the discretion of court officials and Black-White disparities
      remain prominent.

PMID- 25382874
TI  - Inorganic chemistry in nuclear imaging and radiotherapy: current and future
      directions.
AB  - Radiometals play an important role in diagnostic and therapeutic
      radiopharmaceuticals. This field of radiochemistry is multidisciplinary,
      involving radiometal production, separation of the radiometal from its target,
      chelate design for complexing the radiometal in a biologically stable
      environment, specific targeting of the radiometal to its in vivo site, and
      nuclear imaging and/or radiotherapy applications of the resultant
      radiopharmaceutical. The critical importance of inorganic chemistry in the design
      and application of radiometal-containing imaging and therapy agents is described
      from a historical perspective to future directions.

PMID- 25382878
TI  - Effective Degrees of Freedom and Its Application to Conditional AIC for Linear
      Mixed-Effects Models with Correlated Error Structures.
AB  - The effective degrees of freedom is a useful concept for describing model
      complexity. Recently the number of effective degrees of freedom has been shown to
      relate to the concept of conditional Akaike information (cAI) in the mixed
      effects models. This relationship was made explicit under linear mixed-effects
      models with i.i.d. errors, and later also extended to the generalized linear and
      the proportional hazards mixed models. We show that under linear mixed-effects
      models with correlated errors, the number of effective degrees of freedom is
      asymptotically equal to the trace of the usual 'hat' matrix plus the number of
      parameters in the error covariance matrix. Using it one can define a crude
      version of the conditional AIC (cAIC), which is known to be inaccurate due to the
      estimation of unknown variance parameters. We compare this crude version to
      several corrected versions of cAIC for linear mixed models with correlated
      errors, including one that is asymptotically unbiased counting for the unknown
      parameters, but one which is also difficult to compute without specific
      programming for each case of the error correlation structure.

PMID- 25382879
TI  - Relationship quality among cohabitors and marrieds in older adulthood.
AB  - The rapid growth in cohabitation in recent decades has coincided with a
      burgeoning literature on the topic. Yet despite a sustained increase in
      cohabitation among middle-aged and older adults, this group has received little
      research attention. Close relationships are integral to well-being and the
      quality of these relationships has consequences for health, especially among
      older adults. We use data from the National Social Life, Health, and Aging
      Project (NSHAP), a nationally representative sample of 3005 people ages 57-85 to
      compare the relationship quality of older cohabitors versus marrieds. The two
      groups are remarkably similar. Cohabitors and marrieds do not significantly
      differ in their reports of emotional satisfaction, pleasure, openness, time spent
      together, criticism, and demands. Cohabitors are less likely than marrieds to
      report that their relationship is very happy. There is some evidence of gender by
      union type differences. Cohabiting unions among older adults tend to be of
      relatively long duration. Overall, these results indicate that cohabitation may
      operate as an alternative to marriage for older adults.

PMID- 25382880
TI  - HOPE, SELF-ESTEEM, AND SELF-REGULATION: POSITIVE CHARACTERISTICS AMONG MEN AND
      WOMEN IN RECOVERY.
AB  - Hopefulness remains unclear in relation to aspects of self-control and self
      esteem among adults in substance abuse recovery. The present study explored the
      relationship between dispositional hope (agency and pathway) with self-esteem
      (self-liking, self-competency, and self-confidence) and self-regulation (impulse
      control and self-discipline), using a latent variable measurement model and
      structural equation modeling among adults (n = 601) residing in a communal living
      setting for persons in substance abuse recovery. Results showed that multiple
      dimensions of these constructs were significant as individual predictors. With
      persons in recovery, self-regulation included impulsivity control and self
      discipline, while self-esteem reflected self-liking, competence, and a sense of
      self-confidence. Furthermore, both hope-pathways and hope-agency significantly
      related to self-control/impulse control but not self-control/discipline, and self
      esteem/competency was associated with hope-pathways but not hope-agency.

PMID- 25382881
TI  - Characteristics and Life Experiences Associated with Receiving a Rape Disclosure
      within a National Telephone Household Probability Sample of Women.
AB  - Disclosure of rape to informal support sources is relatively common, but not well
      understood. This study expands our limited knowledge of disclosure recipients'
      experience by examining associations between their socio-demographic and life
      experiences with receipt of a rape disclosure and encouragement of the victim to
      formally report her assault. Over 35% of the 3,001 community-residing women in
      this national sample reported receiving a rape disclosure. Women who had a
      personal history of sexual assault, met lifetime diagnostic criteria for
      posttraumatic stress disorder or depression, met past-year diagnostic criteria
      for substance abuse, engaged in monthly binge drinking and non-experimental
      substance use, and sought help for emotional concerns were significantly more
      likely to be recipients. Approximately two-thirds (69%) of disclosure recipients
      encouraged the victim to formally report the rape, and encouragement was also
      significantly associated with these characteristics. Implications of these
      findings for improving the disclosure process are provided.

PMID- 25382882
TI  - Magnetic Pressure as a Scalar Representation of Field Effects in Magnetic
      Suspensions.
AB  - Magnetic microsphere suspensions undergo complex motion when exposed to finite
      sources of the magnetic field, such as small permanent magnets. The computational
      complexity is compounded by a difficulty in choosing a suitable choice of
      visualization tools because this often requires using the magnetic force vector
      field in three dimensions. Here we present a potentially simpler approach by
      using the magnetic pressure. It is a scalar quantity, pm = B2/2MU0, and its
      usefulness has been already demonstrated in applications to magnetohydrodynamics
      and ferrohydrodynamics (where B is the applied field and MU0 = 4pi*10-7 T.m/A).
      The equilibrium distribution of the magnetic bead plug in aqueous suspension is
      calculated as an isosurface of the magnitude of the magnetic pressure pm = const,
      in the field of two permanent magnet blocks calculated from closed formulas. The
      geometry was adapted from a publication on the magnetic bead suspensions in
      microsystems and the predicted bead plug distribution is shown to agree
      remarkably well with the experiment.

PMID- 25382883
TI  - Personal experiences of pregnancy and fertility in individuals with spinal cord
      injury.
AB  - Individuals with spinal cord injuries (SCIs) often face a number of barriers in
      family planning and pregnancy. These barriers can be structural (i.e.
      inaccessible health care provider offices and providers unfamiliar with
      fertility, pregnancy, and SCI) or social (i.e. friends, family, and even
      providers suggesting that individuals with SCI should not have children), and can
      affect both men and women. Additionally, much of the information about SCI and
      pregnancy is from a medical perspective and the psychosocial aspects of pregnancy
      for individuals with SCI have not been considered. 253 men and women with SCI
      were asked about the information they received about SCI and pregnancy, where
      they received this information, and how their SCI affected their family planning.
      The responses shared in this study can be used to inform individuals who work
      with people with SCI to better assist their clients or patients who have
      sustained SCI and are considering pregnancy.

PMID- 25382884
TI  - Using Data Augmentation to Facilitate Conduct of Phase I-II Clinical Trials with
      Delayed Outcomes.
AB  - A practical impediment in adaptive clinical trials is that outcomes must be
      observed soon enough to apply decision rules to choose treatments for new
      patients. For example, if outcomes take up to six weeks to evaluate and the
      accrual rate is one patient per week, on average three new patients will be
      accrued while waiting to evaluate the outcomes of the previous three patients.
      The question is how to treat the new patients. This logistical problem persists
      throughout the trial. Various ad hoc practical solutions are used, none entirely
      satisfactory. We focus on this problem in phase I-II clinical trials that use
      binary toxicity and efficacy, defined in terms of event times, to choose doses
      adaptively for successive cohorts. We propose a general approach to this problem
      that treats late-onset outcomes as missing data, uses data augmentation to impute
      missing outcomes from posterior predictive distributions computed from partial
      follow-up times and complete outcome data, and applies the design's decision
      rules using the completed data. We illustrate the method with two cancer trials
      conducted using a phase I-II design based on efficacy-toxicity trade-offs,
      including a computer stimulation study.

PMID- 25382886
TI  - The Sparse MLE for Ultra-High-Dimensional Feature Screening.
AB  - Feature selection is fundamental for modeling the high dimensional data, where
      the number of features can be huge and much larger than the sample size. Since
      the feature space is so large, many traditional procedures become numerically
      infeasible. It is hence essential to first remove most apparently non-influential
      features before any elaborative analysis. Recently, several procedures have been
      developed for this purpose, which include the sure-independent-screening (SIS) as
      a widely-used technique. To gain the computational efficiency, the SIS screens
      features based on their individual predicting power. In this paper, we propose a
      new screening method via the sparsity-restricted maximum likelihood estimator
      (SMLE). The new method naturally takes the joint effects of features in the
      screening process, which gives itself an edge to potentially outperform the
      existing methods. This conjecture is further supported by the simulation studies
      under a number of modeling settings. We show that the proposed method is
      screening consistent in the context of ultra-high-dimensional generalized linear
      models.

PMID- 25382885
TI  - Identifying Genetic Variants for Addiction via Propensity Score Adjusted
      Generalized Kendall's Tau.
AB  - Identifying replicable genetic variants for addiction has been extremely
      challenging. Besides the common difficulties with genome-wide association studies
      (GWAS), environmental factors are known to be critical to addiction, and
      comorbidity is widely observed. Despite the importance of environmental factors
      and comorbidity for addiction study, few GWAS analyses adequately considered them
      due to the limitations of the existing statistical methods. Although parametric
      methods have been developed to adjust for covariates in association analysis,
      difficulties arise when the traits are multivariate because there is no ready-to
      use model for them. Recent nonparametric development includes U-statistics to
      measure the phenotype-genotype association weighted by a similarity score of
      covariates. However, it is not clear how to optimize the similarity score.
      Therefore, we propose a semiparametric method to measure the association adjusted
      by covariates. In our approach, the nonparametric U-statistic is adjusted by
      parametric estimates of propensity scores using the idea of inverse probability
      weighting. The new measurement is shown to be asymptotically unbiased under our
      null hypothesis while the previous non-weighted and weighted ones are not.
      Simulation results show that our test improves power as opposed to the non
      weighted and two other weighted U-statistic methods, and it is particularly
      powerful for detecting gene-environment interactions. Finally, we apply our
      proposed test to the Study of Addiction: Genetics and Environment (SAGE) to
      identify genetic variants for addiction. Novel genetic variants are found from
      our analysis, which warrant further investigation in the future.

PMID- 25382887
TI  - Examining Sexual Orientation Disparities in Unmet Medical Needs among Men and
      Women.
AB  - Using the National Longitudinal Study of Adolescent Health (N = 13,810), this
      study examines disparities in unmet medical needs by sexual orientation identity
      during young adulthood. We use binary logistic regression and expand Andersen's
      health care utilization framework to identify factors that shape disparities in
      unmet medical needs by sexual orientation. We also investigate whether the well
      established gender disparity in health-seeking behaviors among heterosexual
      persons holds for sexual minorities. The results show that sexual minority women
      are more likely to report unmet medical needs than heterosexual women, but no
      differences are found between sexual minority and heterosexual men. Moreover, we
      find a reversal in the gender disparity between heterosexual and sexual minority
      populations: heterosexual women are less likely to report unmet medical needs
      than heterosexual men, whereas sexual minority women are more likely to report
      unmet medical needs compared to sexual minority men. Finally, this work advances
      Andersen's model by articulating the importance of including social psychological
      factors for reducing disparities in unmet medical needs by sexual orientation for
      women.

PMID- 25382888
TI  - Educational Attainment by Life Course Sexual Attraction: Prevalence and
      Correlates in a Nationally Representative Sample of Young Adults.
AB  - Researchers know relatively little about the educational attainment of sexual
      minorities, despite the fact that educational attainment is consistently
      associated with a range of social, economic, and health outcomes. We examined
      whether sexual attraction in adolescence and early adulthood was associated with
      educational attainment in early adulthood among a nationally representative
      sample of US young adults. We analyzed Waves I and IV restricted data from the
      National Longitudinal Study of Adolescent Health (n=14,111). Sexual orientation
      was assessed using self-reports of romantic attraction in Waves I (adolescence)
      and IV (adulthood). Multinomial regression models were estimated and all analyses
      were stratified by gender. Women attracted to the same-sex in adulthood only had
      lower educational attainment compared to women attracted only to the opposite-sex
      in adolescence and adulthood. Men attracted to the same-sex in adolescence only
      had lower educational attainment compared to men attracted only to the opposite
      sex in adolescence and adulthood. Adolescent experiences and academic performance
      attenuated educational disparities among men and women. Adjustment for adolescent
      experiences also revealed a suppression effect; women attracted to the same-sex
      in adolescence and adulthood had lower predicted probabilities of having a high
      school diploma or less compared to women attracted only to the opposite-sex in
      adolescence and adulthood. Our findings challenge previous research documenting
      higher educational attainment among sexual minorities in the US. Additional
      population-based studies documenting the educational attainment of sexual
      minority adults are needed.

PMID- 25382889
TI  - A unified discontinuous Galerkin framework for time integration.
AB  - We introduce a new discontinuous Galerkin approach for time integration. On the
      basis of the method of weighted residual, numerical quadratures are employed in
      the finite element time discretization to account for general nonlinear ordinary
      differential equations. Many different conditions, including explicit, implicit,
      and symplectic conditions, are enforced for the test functions in the variational
      analysis to obtain desirable features of the resulting time-stepping scheme. The
      proposed discontinuous Galerkin approach provides a unified framework to derive
      various time-stepping schemes, such as low-order one-step methods, Runge-Kutta
      methods, and multistep methods. On the basis of the proposed framework, several
      explicit Runge-Kutta methods of different orders are constructed. The derivation
      of symplectic Runge-Kutta methods has also been realized. The proposed framework
      allows the optimization of new schemes in terms of several characteristics, such
      as accuracy, sparseness, and stability. The accuracy optimization is performed on
      the basis of an analytical form of the error estimation function for a linear
      test initial value problem. Schemes with higher formal order of accuracy are
      found to provide more accurate solutions. We have also explored the optimization
      potential of sparseness, which is related to the general compressive sensing in
      signal/imaging processing. Two critical dimensions of the stability region, that
      is, maximal intervals along the imaginary and negative real axes, are employed as
      the criteria for stability optimization. This gives the largest Courant
      Friedrichs-Lewy time steps in solving hyperbolic and parabolic partial
      differential equations, respectively. Numerical experiments are conducted to
      validate the optimized time-stepping schemes.

PMID- 25382890
TI  - The Lived Experience of Welfare Reform in Drug-Using Welfare-Needy Households in
      Inner-City New York.
AB  - Welfare reform has transformed a needs-based family income support into temporary
      assistance for persons entering the workforce. This paper uses observations from
      an ethnographic study covering the period from 1995-2001 to examine the impact on
      drug-using welfare-needy households in inner-city New York. The analysis suggests
      that studies may underestimate the extent to which substance use is associated
      with welfare problems. Nearly all of these already distressed households lost
      their AFDC/TANF benefits, had difficulty with work programs, and were having more
      difficulty covering expenses. The conclusion highlights ways to better study this
      population and policy initiatives that could help them reform their impoverished
      lives for themselves and their children.

PMID- 25382891
TI  - Unpacking the Effect of Parental Monitoring on Early Adolescent Problem Behavior:
      Mediation by Parental Knowledge and Moderation by Parent-Youth Warmth.
AB  - This study explores the monitoring process longitudinally among a sample of rural
      early adolescents and addresses two research questions (1) Does maternal
      knowledge mediate the relationship between three aspects of the parental
      monitoring process and adolescent problem behavior: active parent monitoring
      efforts, youth disclosure, and parental supervision? (2) Are these meditational
      pathways moderated by the affective quality of the parent-child relationship?
      Parent efforts to monitor youth and youth disclosure in the Fall of Grade 6
      predicted substance use and delinquency in Grade 8. These relations were mediated
      by increases in maternal knowledge assessed in the Spring of Grade 6, suggesting
      that the protective effects of these constructs are partially indirect.
      Supervision was not significantly related to maternal knowledge or problem
      behavior. Parent efforts to monitor were more strongly related to maternal
      knowledge in families with high levels of positive affect than in families with
      low levels of positive affect.

PMID- 25382893
TI  - Thermal adaptation of cellular membranes in natural populations of Drosophila
      melanogaster.
AB  - Changes in temperature disrupt the fluidity of cellular membranes, which can
      negatively impact membrane integrity and cellular processes. Many ectotherms,
      including Drosophila melanogaster (Meigen), adjust the glycerophospholipid
      composition of their membranes to restore optimal fluidity when temperatures
      change, a type of trait plasticity termed homeoviscous adaptation.Existing data
      suggest that plasticity in the relative abundances of the glycerophospholipids
      phosphatidylethanolamine (PE) and phosphatidylcholine (PC) underlies cellular
      adaptation to temporal variability in the thermal environment. For example,
      laboratory populations of D. melanogaster evolved in the presence of temporally
      variable temperatures have greater developmental plasticity of the ratio of PE to
      PC (PE/PC) and greater fecundity than do populations evolved at constant
      temperatures.Here, we extend this work to natural populations of D. melanogaster
      by evaluating thermal plasticity of glycerophospholipid composition at different
      life stages, in genotypes isolated from Vermont, Indiana and North Carolina, USA.
      We also quantify the covariance between developmental and adult (reversible)
      plasticity, and between adult responses of the membrane to cool and warm thermal
      shifts.As predicted by physiological models of homeoviscous adaptation, flies
      from all populations decrease PE/PC and the degree of lipid unsaturation in
      response to warm temperatures. Furthermore, these populations have diverged in
      their degree of membrane plasticity. Flies from the most variable thermal
      environment (Vermont, USA) decrease PE/PC to a greater extent than do other
      populations when developed at a warm temperature, a pattern that matches our
      previous observation in laboratory-evolved populations. We also find that
      developmental plasticity and adult plasticity of PE/PC covary across genotypes,
      but that adult responses to cool and warm thermal shifts do not.When combined
      with our previous observations of laboratory-evolved populations, our findings
      implicate developmental plasticity of PE/PC as a mechanism of thermal adaptation
      in temporally variable environments. While little is known about the genetic
      bases of plastic responses to temperature, our observations suggest that both
      environmentally sensitive and environmentally specific alleles contribute to
      thermal adaptation of membranes, and that costs of plasticity may arise when the
      adult environment differs from that experienced during development.

PMID- 25382894
TI  - Stress-Transfer Micromechanics For Fiber Length with a Photocure Vinyl Ester
      Composite.
AB  - The objective was to test how increasing fiber length above the critical length
      would influence mechanical properties and fracture crack propagation.
      Micromechanics considering fiber/matrix stress-transfer was used to evaluate the
      results in addition to a shear debonding volume percent correction term necessary
      for the final analysis. Fiber lengths of 0.5, 1.0, 2.0, 3.0, and 6.0 mm with 9
      MUm diameters were added into a photocure vinyl ester particulate-filled
      composite at a uniform 28.2 vol%. Mechanical flexural testing was performed using
      four-point fully articulated fixtures for samples measuring 2 * 2 * 50 mm3 across
      a 40 mm span. Fiber length correlated with improved mechanical properties for
      flexural strength, modulus, yield strength, strain, work of fracture, and strain
      energy release, p < 0.001. In addition, sample fracture depth significantly
      decreased with increasing fiber lengths, p < 0.00001. All mechanical properties
      correlated significantly as predictors for fracture failure, p < 0.000001, and as
      estimators for each other, p < 0.0001. The stress-transfer micromechanics for
      fiber length were improved upon for strength by including a simple correction
      factor to account for loss of fiber volume percent related to cracks deflecting
      around debonded fiber ends. In turn, the elastic property of modulus was shown to
      exhibit a tendency to follow stress-transfer micromechanics.

PMID- 25382892
TI  - Multiscale Multiphysics and Multidomain Models I: Basic Theory.
AB  - This work extends our earlier two-domain formulation of a differential geometry
      based multiscale paradigm into a multidomain theory, which endows us the ability
      to simultaneously accommodate multiphysical descriptions of aqueous chemical,
      physical and biological systems, such as fuel cells, solar cells, nanofluidics,
      ion channels, viruses, RNA polymerases, molecular motors and large macromolecular
      complexes. The essential idea is to make use of the differential geometry theory
      of surfaces as a natural means to geometrically separate the macroscopic domain
      of solvent from the microscopic domain of solute, and dynamically couple
      continuum and discrete descriptions. Our main strategy is to construct energy
      functionals to put on an equal footing of multiphysics, including polar (i.e.,
      electrostatic) solvation, nonpolar solvation, chemical potential, quantum
      mechanics, fluid mechanics, molecular mechanics, coarse grained dynamics and
      elastic dynamics. The variational principle is applied to the energy functionals
      to derive desirable governing equations, such as multidomain Laplace-Beltrami
      (LB) equations for macromolecular morphologies, multidomain Poisson-Boltzmann
      (PB) equation or Poisson equation for electrostatic potential, generalized Nernst
      Planck (NP) equations for the dynamics of charged solvent species, generalized
      Navier-Stokes (NS) equation for fluid dynamics, generalized Newton's equations
      for molecular dynamics (MD) or coarse-grained dynamics and equation of motion for
      elastic dynamics. Unlike the classical PB equation, our PB equation is an
      integral-differential equation due to solvent-solute interactions. To illustrate
      the proposed formalism, we have explicitly constructed three models, a
      multidomain solvation model, a multidomain charge transport model and a
      multidomain chemo-electro-fluid-MD-elastic model. Each solute domain is equipped
      with distinct surface tension, pressure, dielectric function, and charge density
      distribution. In addition to long-range Coulombic interactions, various non
      electrostatic solvent-solute interactions are considered in the present modeling.
      We demonstrate the consistency between the non-equilibrium charge transport model
      and the equilibrium solvation model by showing the systematical reduction of the
      former to the latter at equilibrium. This paper also offers a brief review of the
      field.

PMID- 25382895
TI  - Micromechanics for Fiber Volume Percent With a Photocure Vinyl Ester Composite.
AB  - Micromechanics for fiber volume percent (Vf) from 0.0Vf to 54.0 Vf were conducted
      using (3 mm long * 9 um diameter) high-purity quartz fibers in a visible-light
      vinyl ester particulate-filled photocure resin. MTS fully articulated four-point
      bend fixtures were used with a 40 mm test span and 50 * 2 * 2 mm3 sample
      dimensions. Specimens were tested following the combined modified ASTM standards
      for advanced ceramics ASTM-C-1161-94 and polymers ASTM-D-6272-00 for modulus,
      flexural strength, and yield strength. Experimental data provided reliable
      statistical support for the dominant fiber contribution expressed through the
      rule-of-mixtures theory as a valid representation of micromechanical physics. The
      rule-of-mixtures micromechanics described by Vf could explain 92, 85, and 78% of
      the variability related to modulus, flexural strength, and yield strength
      respectively. Statistically significant improvements with fiber addition began at
      10.3Vf for modulus, 5.4Vf for flexural strength, and 10.3Vf for yield strength, p
      < 0.05. In addition, correlation matrix analysis was performed for all mechanical
      test data. An increase in Vf correlated significantly with increases in modulus,
      flexural strength, and yield strength as measured by the four-point bending test,
      p < 10-10. All mechanical properties in turn correlated highly significantly with
      one another, p < 10-9.

PMID- 25382896
TI  - Bimetallic Zirconium Amine Bis(phenolate) Polymerization Catalysts: Enhanced
      Activity and Tacticity Control for Polyolefin Synthesis.
AB  - Binucleating multidentate amine bis(phenolate) ligands with rigid terphenyl
      backbones were designed to support two zirconium centers locked in close
      proximity. Polymerizations of propylene or 1-hexene with the synthesized
      bimetallic precatalysts resulted in polymers with significantly higher
      isotacticity (up to 79% mmmm) in comparison to the stereoirregular polymers
      produced with previously reported Cs -symmetric monometallic analogues. The
      bimetallic precatalysts also display higher activity (up to 124 kg of poly(1
      hexene) (mmol of Zr)-1 h-1), in comparison to the monometallic analogues, and
      among the highest activities reported for nonmetallocene catalysts. The
      stereocontrol is consistent with a bimetallic mechanism involving remote steric
      interactions with the ligand sphere of the second metal center.

PMID- 25382897
TI  - Elderly Immigrants' Labor Supply Response to Supplemental Security Income.
AB  - This paper examined how the 1996 Personal Responsibility and Work Opportunity
      Reconciliation Act, which banned Supplemental Security Income to the majority of
      elderly immigrants, affected their employment, retirement, and family incomes.
      The policy was found to be associated with a 3.5 percentage point (9.5 percent)
      increase in the employment and a 3.8 percentage point (7 percent) decrease in the
      retirement of foreign-born elderly men. Partly as a result of their employment
      response, SSI ineligibility and the consequent decline in SSI receipt did not
      have any statistically significant effects on the family incomes of elderly
      foreign-born men. Noncitizen elderly women, on the other hand, did not experience
      any increase in employment, and those without family support suffered a 10 to 17
      percent decline in income. These findings suggest that access to SSI did not
      create work disincentives for noncitizen elderly women and that SSI restrictions
      have imposed financial hardship on those without any family support, many of whom
      perhaps cannot effectively increase their employment.

PMID- 25382898
TI  - A Figure-of-Merit for Designing High-Performance Inductive Power Transmission
      Links.
AB  - Power transfer efficiency (PTE) and power delivered to the load (PDL) are two key
      inductive link design parameters that relate to the power source and driver
      specs, power loss, transmission range, robustness against misalignment,
      variations in loading, and interference with other devices. Designers need to
      strike a delicate balance between these two because designing the link to achieve
      high PTE will degrade the PDL and vice versa. We are proposing a new figure-of
      merit (FoM), which can help designers to find out whether a two-, three-, or four
      coil link is appropriate for their particular application and guide them through
      an iterative design procedure to reach optimal coil geometries based on how they
      weigh the PTE versus PDL for that application. Three design examples at three
      different power levels have been presented based on the proposed FoM for
      implantable microelectronic devices, handheld mobile devices, and electric
      vehicles. The new FoM suggests that the two-coil links are suitable when the
      coils are strongly coupled, and a large PDL is needed. Three-coil links are the
      best when the coils are loosely coupled, the coupling distance varies
      considerably, and large PDL is necessary. Finally, four-coil links are optimal
      when the PTE is paramount, the coils are loosely coupled, and their relative
      distance and alignment are stable. Measurement results support the accuracy of
      the theoretical design procedure and conclusions.

PMID- 25382900
TI  - AGE DIFFERENCES IN RISKY DECISIONS: THE ROLE OF ANTICIPATED EMOTIONS.
AB  - The present study investigated the role of anticipated emotions in risky
      decisions of young and older adults. Young and older adults were asked to make a
      choice between an alternative that may have either a very positive or a very
      negative consequence and an alternative that was relatively safe. Meanwhile, they
      rated their anticipated emotions if the results turned out to be positive or
      negative. Older adults' decisions were significantly influenced by anticipated
      positive emotions (e.g., happiness). Younger adults' decisions were associated by
      anticipated negative emotions (e.g., regret). These results have implications in
      decision making of older adults.

PMID- 25382899
TI  - Prognostic value of Rab27B nuclear expression in gastrointestinal stromal tumors.
AB  - Rab proteins of the endocytosis and exocytosis pathways both play critical roles
      in cancer progression, and Rab27B has a significant relationship with several
      types of human cancer. However, the association between Rab27B expression and
      clinical features to determine its clinicopathological significance in
      gastrointestinal tumor (GIST) has not been investigated. To examine the
      expression of Rab27B in GIST and investigate the association between its
      expression and patient prognosis, immunohistochemistry analysis with tissue
      microarray was used to evaluate expression of Rab27B in 162 patients with GIST.
      The relationship between Rab27B expression and patient prognosis was analyzed.
      High nuclear staining of Rab27B was detected in 88 of 162 (54.32%) GIST tissues.
      Positive staining of Rab27B was significantly associated with tumor size (P =
      0.006), mitotic index (P = 0.013), Armed Forces Institute of Pathology Miettinen
      risk classification (P = 0.002), and tumor grade (P = 0.021). Kaplan-Meier
      survival curves showed that GIST patients with low Rab27B nuclear expression (P =
      0.038) and mitotic index <5 per 50 high-power fields (P = 0.029) had a more
      favorable prognosis. These findings indicate that Rab27B nuclear expression is
      correlated with several clinicopathological features of GIST patients, and it may
      serve as an unfavorable prognostic marker. 

PMID- 25382901
TI  - Preventing Mother To Child Transmission of HIV - Current strategies.

PMID- 25382902
TI  - Efficacy of single dose Nevirapine in reducing viral load in HIV positive mother
      in labour and transmission of HIV infection to new born babies as part of
      prevention of parent to child transmission.
AB  - BACKGROUND: Prevention of parent to child transmission (PPTCT) program was
      initiated in Armed Forces to reduce the vertical transmission of HIV by
      instituting single dose Nevirapine (sdNVP) in untreated HIV positive mothers in
      labour. The aim of this study was to evaluate the role of sdNVP to decrease viral
      load of HIV infected mother during labour and its efficacy in prevention of
      mother to child transmission of HIV. METHODS: Thirty antenatal women tested
      positive for HIV at our PPTCT centre and delivered between Jan 2006 and May 2008
      were evaluated. During labour these women were given sdNVP. Newborns were given
      syrup Nevirapine. The babies were tested for HIV infection at 48 h and six weeks
      after delivery. RESULTS: Thirty HIV positive women delivered at our centre and
      four newborns were found positive for HIV infection at 48 h. After six weeks
      interval three neonates were detected for HIV infection as one infant at six
      weeks was found to be negative for HIV infection. CONCLUSION: The protection rate
      of Nevirapine in untreated HIV positive women is not ideal. It is recommended
      that all HIV positive women should be offered Highly Active Antiretroviral
      therapy as primary mode for PPTCT.

PMID- 25382903
TI  - Monitoring of response to therapy with imatinib mesylate in Chronic Myeloid
      Leukemia in chronic phase (CML-CP).
AB  - BACKGROUND: The BCR-ABL tyrosine kinase is a well validated therapeutic target in
      Chronic Myeloid Leukemia (CML). Imatinib mesylate (IM), a tyrosine kinase
      inhibitor is highly effective in the treatment of chronic phase CML. BCR - ABL
      transcripts have been well established as a molecular marker to document response
      to therapy in CML. Periodic monitoring of this marker helps in evolving
      therapeutic strategies with IM and also in diagnosing early relapse. This study
      was undertaken to monitor therapeutic response to IM in CML in chronic phase (CML
      CP) by assessing BCR-ABL by real time quantitative PCR (RQ-PCR) techniques and to
      determine the effectiveness of the Indian generic IM. METHODS: One hundred
      consecutive patients of CML in chronic phase (CML-CP) were treated with an Indian
      generic of IM. Eighty-five patients were evaluable at 12 months of therapy. At
      entry, diagnosis of CML-CP was confirmed by FISH and RQ-PCR. Response to therapy
      was monitored by assessing BCR-ABL levels by RQ-PCR at 6 and 12 months of
      therapy. Regular follow up of patients was done to evaluate the safety profile of
      IM used in these patients. RESULTS: Complete hematological response (CHR) rates
      at 3, 6, 9 and 12 months were 92%, 94%, 100% and 100% respectively. The total
      molecular response at 12 months was 43.52% of which complete molecular response
      (CMR) was noted in 17.64% and major molecular response (MMR) was observed in
      25.88%. A cumulative survival probability of 0.8 was observed. CONCLUSION: The
      Indian generic molecule of IM is effective in the treatment of CML-CP. The cost
      of Indian generic molecule is less than Rs. 10,000 per month there by making this
      affordable for large number of CML-CP patients in India.

PMID- 25382904
TI  - Whipple's pancreaticoduodenectomy: Outcomes at a tertiary care hospital.
AB  - BACKGROUND: Pancreaticoduodenectomy is a formidable surgery and was associated
      with high morbidity and mortality. Though the mortality rates have steadily
      improved, morbidity continues to be high. There is lack of published data on
      outcomes following pancreaticoduodenectomy in Armed Forces hospitals. The aim of
      this study was to analyze the short term outcomes at our center and to compare it
      with the published literature. METHODS: A retrospective review of prospectively
      maintained data base was done. Preoperative, intraoperative and postoperative
      data was analyzed with emphasis on the morbidity and mortality rates. Follow up
      data was analyzed to look at disease recurrence. RESULTS: Between Jan 2008 and
      March 2014, 69 patients underwent Whipple's pancreaticoduodenectomy with a median
      age of 64 years. All had a malignant etiology with periampullary carcinoma being
      the commonest (42%). Overall, intra-abdominal complications occurred in 46% of
      patients which included postoperative pancreatic fistula (20%) and delayed
      gastric emptying (24%). The mortality rate for the whole was 11% which reduced to
      8% in the second half of the study. CONCLUSION: The short term outcomes at our
      center were comparable to those in published literature. The mortality rates
      showed a decreasing trend with time.

PMID- 25382905
TI  - Safety and effectiveness of bubble continuous positive airway pressure in preterm
      neonates with respiratory distress.
AB  - BACKGROUND: Studies on Bubble Continuous Positive Airway Pressure (B-CPAP) as
      respiratory support for neonates are few. The aim of our study was to determine
      the efficacy and safety of B-CPAP in preterm neonates requiring respiratory
      support. METHODS: A prospective observation study was done on 50 preterm babies
      requiring respiratory support for mild to moderate respiratory distress. Support
      was given with short, nasal cannulae. Surfactant was administered when indicated.
      Monitoring was done clinically, with pulse oximeter, radiologically and with
      blood gases. Staff members were also asked their views. Follow-up was done for 3
      months. RESULTS: The mean gestational age was 32.46 (+3.23) weeks and mean birth
      weight 1454.4 (+487.42) g. Respiratory Distress Syndrome was the commonest
      indication (30/50). The mean maximum pressure was 6.04 cm H2O and mean maximum
      FiO2 was 72.16%. Mean maximum paO2, paCO2 and mean minimum paCO2 were 92.93 mm Hg
      (+16.97), 52.36 mm Hg (+ 7.78) and 36.46 mm Hg (+ 4.95) respectively. Early
      initiation resulted in lesser duration of support. Failure rate was 30%. Apnoea,
      >1 dose surfactant and late initiation had a statistically higher incidence of
      failure. Main complications were skin abrasions (30%), feed intolerance (26%) and
      gastric distension (26%). Survival rate was 94%. 68% of staff felt that it was as
      easy to use and 88% felt it was more reliable than standard CPAP. CONCLUSIONS:
      Bubble Continuous Positive Airway Pressure is safe, efficacious and easy to use
      in preterm neonates with mild to moderate respiratory distress.

PMID- 25382906
TI  - Frequency doubling technology and standard automated perimetry in detection of
      glaucoma among glaucoma suspects.
AB  - BACKGROUND: Frequency Doubling perimetry (FDT) has been found to precede visual
      loss detected by standard automated perimetry (SAP) by as much as four years and
      the initial development of glaucomatous visual field loss as measured by SAP was
      found to occur in regions that had previously demonstrated abnormalities on FDT
      testing. METHODS: A study on 55 glaucoma suspects (determined as per American
      Academy Guidelines, Preferred Practice Pattern, Oct 2010), was compared to 50
      healthy participants (HP). Both glaucoma suspects and HP underwent SAP and FDT in
      random order. Only reliable fields were compared. RESULTS: Mean deviation of FDT
      Matrix was significantly lower than SAP SITA in suspect and healthy group ; two
      devices showed significant correlation amongst both groups (suspects p = 0.002,
      healthy p = 0.011). Significant difference was found in PSD of SAP SITA and FDT
      Matrix (p = 0.001) in the glaucoma suspect group, PSD of FDT Matrix was
      significantly higher than PSD of SAP SITA in the healthy group (p < 0.001). PSD
      of SAP SITA significantly correlated with FDT Matrix PSD in glaucoma group (r =
      0.579; p = 0.001) but no significant correlation found in healthy group (r =
      0.153; p = 0.290). Percentages of normal test locations significantly higher in
      FDT Matrix compared to SAP SITA in glaucoma suspects and healthy participants.
      CONCLUSION: FDT correlates well with SAP and may be used for patients who are
      unable to perform well and reliably with SAP but does not show any features of
      earlier glaucoma changes in this study.

PMID- 25382907
TI  - Influence of skin-to-muscle and muscle-to-bone thickness on depth of needle
      penetration in adults at the deltoid intramuscular injection site.
AB  - BACKGROUND: THE OBJECTIVES OF THE STUDY WERE TO ESTIMATE THE FOLLOWING IN ADULTS
      OF INDIAN ORIGIN: a) Gender and side differences in the skin-to-muscle (SM) and
      muscle-to-bone thickness (MB) at the deltoid intramuscular injection site; b)
      Correlation of SM thickness with the BMI, age and gender; c) The prevalence of
      under and over-penetration assuming a standard needle length of 25 mm and
      following prescribed guidelines for IM injection. METHODS: The SM, MB and skin-to
      bone (SB) thicknesses were bilaterally estimated in two hundred adult Indian
      subjects (100 male and 100 female) using an ultrasound probe at a pre-determined
      point on the upper arms of the subjects. The BMI of each subject was calculated.
      The unpaired sample 't' test and paired 't' test were used to analyse differences
      between groups. Pearson's correlation coefficient was used in correlation
      analysis and suitable linear regression equations were generated. RESULTS:
      Females had a significantly higher SM thickness and lower MB thickness. The SM
      thickness was significantly greater on the left side, while the SB and MB
      thickness were significantly greater on the right. Multiple linear regression
      equations for both the dominant and non-dominant arms had good model fit
      properties. Under-penetration would have occurred in 2 (1%) subjects while over
      penetration would have occurred in 50% of the subjects. CONCLUSION: Over
      penetration of deltoid IM injections is likely to be more prevalent as compared
      to under-penetration. Therefore, the technique of IM injection needs to be
      modified based on the body type of the individual patient.

PMID- 25382908
TI  - Use of Otoacoustic Emissions (OAE) to detect sub-clinical inner ear damage in
      divers of the Indian Navy.
AB  - BACKGROUND: Professional Divers are at a high risk of Sensorineural Hearing
      Impairment. Divers may sustain sub-clinical hearing loss that is not identified
      on pure tone audiometry (PTA). Otoacoustic Emissions (OAE) reflect the functional
      status of the Outer Hair Cells. OAE testing constitutes the only non-invasive
      means of objective cochlear investigation and may be a more sensitive measure
      than PTA in identifying sub-clinical hearing loss. METHODS: This cross-sectional
      study was performed to determine utility of Otoacoustic Emissions testing in
      detecting sub-clinical Inner Ear damage in divers of Indian Navy. Transient
      Evoked Otoacoustic Emissions (TEOAE) levels were measured in 50 audiologically
      asymptomatic ship divers of Indian Navy and compared with control group
      comprising of 50 normal hearing individuals. RESULTS: No statistically
      significant differences were observed between the study and control group. Also
      no correlation was observed between diving years and TEOAE levels. There was no
      correlation greater than -0.49 between diving years and TEOAE SNR. CONCLUSIONS:
      We concluded that TEOAE levels are not a sensitive tool in identifying ships
      divers without any history of noise exposure at risk for developing hearing loss.

PMID- 25382909
TI  - Study of human sperm motility post cryopreservation.
AB  - BACKGROUND: Cryopreservation of spermatozoa is a widely used technique to
      preserve the fertility of males. It can also benefit the armed forces personnel
      who are to be sent for long recruitments, while leaving their families behind.
      This study, apart from studying the effects of freezing and thawing, reveals the
      effect of the post thaw interval on the motility of the human spermatozoa and
      thus widens the insemination window period. METHODS: A detailed semen analysis
      was carried out as per the WHO guidelines for 25 samples. The samples were then
      washed, analysed and frozen in liquid nitrogen. The semen samples were
      subsequently thawed and similarly analysed after 20 min and 40 min of thawing.
      This was then followed by statistical analysis of the comparative motilities.
      RESULTS: Motility of sperms is found to decrease after cryopreservation. However,
      the study revealed that after thawing a significant increase in the motility of
      the sperms was noted with the progression of time (p < 0.05). CONCLUSION: By
      simulating conditions similar to the in vivo conditions for the post thaw semen
      samples, we can safely wait, confirm the parameters like motility and count, and
      then inseminate the samples instead of blindly inseminating them immediately
      after thawing.

PMID- 25382910
TI  - Stigma of mental illness: A study in the Indian Armed Forces.
AB  - BACKGROUND: Stigma against mental illness exists across all countries. Stigma
      devalues the ill person and their relatives and denies them from attaining their
      rightful place in society. Stigma also prevents the ill person from seeking help.
      Stigma in the Armed Forces of UK and USA has been identified as a barrier to help
      seeking and a cause for concern as it could affect operational efficiency.
      However, studies conducted in the services of this country are lacking. Hence we
      decided to measure stigma perceived by patients and caregivers of the mentally
      ill and to assess stigma regarding the mentally ill patients and their
      caregivers, in the general population. METHODS: A cross sectional survey of
      patients (302), their caregivers (98), and members of the general population
      (102) who had no relatives suffering from mental illness was done. The patients
      were given the Stigma Scale developed by King et al. The caregivers (98) were
      given the devaluation of consumers scale and devaluation of consumer families
      scale developed by Struening et al. RESULTS: 90% of patients admitted to
      experiencing stigma. 86% of patients had experienced discrimination. Females
      experienced more discrimination than males. Stigma perceived was irrespective to
      age, mental status, rank and education of the patient. Caregivers perceived
      stigma and felt blamed by the community. Members of the general population gave
      similar responses. CONCLUSIONS: Study has brought out the high levels of stigma
      faced by the patients and their caregivers. High levels of stigma observed are a
      barrier to care.

PMID- 25382911
TI  - Comparison of different regimes of misoprostol for the termination of early
      pregnancy failure.
AB  - BACKGROUND: Nearly 20% of all confirmed pregnancies end in spontaneous abortion.
      Misoprostol's use in early pregnancy failure is varied and dose and route are not
      well established. The aim of this study was to compare the efficacy and the side
      effects of different regimes of misoprostol in causing expulsion of products of
      conception in early pregnancy failure. METHOD: Women patients with an ultrasound
      diagnosis of early pregnancy failure, less than 12 weeks gestation were divided
      into two, Group-A: tab. Misoprostol 800 mcg 6 hourly vaginally, upto 3 doses.
      Group-B tablet misoprostol 600 mcg 6 hourly, sublingually for 3 doses. All
      observations were noted and statistical analyzed. RESULTS: Mean gestational age
      was 7.93 weeks. Mean induction abortion interval 18.183 h. Women patients with
      less than six weeks gestational age had least mean induction-abortion interval
      time, 15.75 +/- 2.82 h in vaginal group but was highest in sublingual group 22 +/
      2 h and 18.43 h in overall (P = 0.02). Though after 8 weeks, both routes were
      equally effective. Mean dose required in group-A was 20044 mcg and in group-B was
      1564 mcg (P < 0.001). Efficacy of protocol was 88.89% in group-A and 92.85% in
      group-B. CONCLUSION: Both regimes had comparable efficacy, acceptability (90%)
      and side effects. In women patients less than six weeks period of gestation, the
      vaginal (800 mcg) route was distinctly superior, in women patients with 6-8 weeks
      the sublingual (600 mcg) route was more advantageous. The correct dose must be
      used for the route chosen. The route of administration should be decided in
      accordance with the preference of the patient and the clinical situation.

PMID- 25382912
TI  - Evolving surgical prosthetic rehabilitation protocol for success of dental
      implant placed in distracted alveolar ridge.
AB  - BACKGROUND: Remodelling of bone in the form of resorption generally follows the
      extraction of a tooth. During all stages of atrophy of the alveolar ridge,
      characteristic shapes result from the resorptive process, as influenced by
      anatomic alterations in the alveolar bone. Various ridge augmentation procedures
      have been documented as predictable means of establishing new vital bone for
      implant placement, out of which distraction osteogenesis is one such modality.
      Hence the following study has been conducted to evolve a surgico- prosthetic
      rehabilitation protocol in grossly atrophic alveolar ridge by distraction
      osteogenesis and subsequent implant placement and to provide an effective
      alternative to lost dental tissue to serving soldiers, their families and ex
      servicemen of the Indian Army in a cost effective manner. METHODS: A total of 30
      patients with ridge defects in age group between 18 to 70 years were selected for
      the study. The net success rate of distraction procedure was 93.33% (100% in
      maxilla and 80% in mandible) with 2 cases deemed as failures out of a total of 30
      cases. The average amount of defect compensated was 76.1% (85.1% and 59.5% in
      maxilla and mandible respectively). RESULTS: For the implant surgical procedure
      the success rate was 100% and subsequently prosthetic rehabilitation on implants
      was proved to be successful. CONCLUSION: Distraction ostoeogenesis of an
      atrophied ridge for further implant placement certainly proves to be successful
      procedure by this study. Further studies in the same procedure using a larger
      sample size will definitely be more beneficial.

PMID- 25382914
TI  - Demineralization of drinking water: Is it prudent?
AB  - Water is the elixir of life. The requirement of water for very existence of life
      and preservation of health has driven man to devise methods for maintaining its
      purity and wholesomeness. The water can get contaminated, polluted and become a
      potential hazard to human health. Water in its purest form devoid of natural
      minerals can also be the other end of spectrum where health could be adversely
      affected. Limited availability of fresh water and increased requirements has led
      to an increased usage of personal, domestic and commercial methods of
      purification of water. Desalination of saline water where fresh water is in
      limited supply has led to development of the latest technology of reverse osmosis
      but is it going to be safe to use such demineralized water over a long duration
      needs to be debated and discussed. 

PMID- 25382913
TI  - Bearing surfaces in hip replacement - Evolution and likely future.
AB  - Total hip arthroplasty has evolved from the first total hip arthroplasty in 1938,
      through the revolutionization of hip arthroplasty by principles of low friction
      arthroplasty introduced by Sir John Charnley in 1960s to the present state of the
      art implants and techniques. The main concern regarding failure of total hip
      arthroplasty has been the biological response to particulate polyethylene debris
      generated by conventional metal on polyethylene bearing surfaces leading to
      osteolysis and aseptic loosening of the prosthesis. Therefore, recent research
      has been focussing on alternative bearing surfaces to reduce the particulate
      debris generated. These bearing surfaces include ceramic-polyethylene, metal
      metal as well as ceramic-ceramic articulations and have demonstrated lesser
      friction rates as well as significantly lower wear rates as compared to widely
      used metal on polyethylene surfaces. Clinical experience until now has shown that
      metal on metal articulations have significant safety concerns whereas metal-on
      highly crosslinked polyethylene, ceramic on ceramic and ceramic on highly
      crosslinked polyethylene articulations have shown encouraging results to hold
      promise for wider use in younger and more active patients. This review article
      discusses positives and drawbacks of various bearing surfaces in current clinical
      use in total hip arthroplasty as well as briefly explores the newer technologies
      on the horizon which may even further decrease wear and improve total hip
      arthroplasty survivorship. 

PMID- 25382915
TI  - Epidemiology of injuries in rural Wardha, central India.
AB  - Injury is a major public health problem in India. As very few studies are
      available from rural areas, hence the present study was carried out to study the
      epidemiology of injuries in the rural areas of Maharashtra. A cross-sectional
      study was carried out in Primary Health Centres (PHC) of a district in
      Maharashtra. 4790 subjects were studied using a two stage sampling technique.
      During last one year, 19.0% (95% CI: 17.7%-19.9%) had at least one injury.
      Majority of injuries (94.0%) were unintentional while assault and suicide related
      injuries were 37 (4.1%) and 10 (1.1%) respectively. Age, sex, education,
      occupation and socio-economic status were significantly associated with injuries.

PMID- 25382916
TI  - Recurrent negative pressure pulmonary oedema after tracheal extubation.

PMID- 25382917
TI  - Imaging of Huntington's disease.

PMID- 25382918
TI  - An unusual case of generalised eruptive syringoma in an adult male.

PMID- 25382919
TI  - Acute fatty liver of pregnancy.

PMID- 25382920
TI  - Sigmoid colon as a content of congenital inguinal hernia: A rare presentation.

PMID- 25382921
TI  - Anti-HIV-1 antibody detection in urine.

PMID- 25382922
TI  - Reply.

PMID- 25382923
TI  - Efficacy of contrast grey scale ultrasound in characterization of hepatic focal
      lesions.

PMID- 25382924
TI  - Reply.

PMID- 25382925
TI  - Reply.

PMID- 25382926
TI  - Letter to the editor.

PMID- 25382927
TI  - Gamma, Gaussian and logistic distribution models for airborne pollen grains and
      fungal spore season dynamics.
AB  - The characteristics of a pollen season, such as timing and magnitude, depend on a
      number of factors such as the biology of the plant and environmental conditions.
      The main aim of this study was to develop mathematical models that explain
      dynamics in atmospheric concentrations of pollen and fungal spores recorded in
      Rzeszow (SE Poland) in 2000-2002. Plant taxa with different characteristics in
      the timing, duration and curve of their pollen seasons, as well as several fungal
      taxa were selected for this analysis. Gaussian, gamma and logistic distribution
      models were examined, and their effectiveness in describing the occurrence of
      airborne pollen and fungal spores was compared. The Gaussian and differential
      logistic models were very good at describing pollen seasons with just one peak.
      These are typically for pollen types with just one dominant species in the flora
      and when the weather, in particular temperature, is stable during the pollination
      period. Based on s parameter of the Gaussian function, the dates of the main
      pollen season can be defined. In spite of the fact that seasonal curves are often
      characterised by positive skewness, the model based on the gamma distribution
      proved not to be very effective.

PMID- 25382928
TI  - An airborne actinobacteria Nocardiopsis alba isolated from bioaerosol of a
      mushroom compost facility.
AB  - Actinobacteria are widely distributed in many environments and represent the most
      important trigger to the occupant respiratory health. Health complaints,
      including hypersensitivity pneumonitis of the workers, were recorded in a
      mushroom compost facility (MCF). The studies on the airborne bacteria were
      carried out to find a possible microbiological source of these symptoms. Culture
      analysis of compost bioaerosols collected in different location of the MCF was
      performed. An assessment of the indoor microbial exposure revealed bacterial
      flora of bioaerosol in the mushroom compost facility represented by Bacillus,
      Geobacillus, Micrococcus, Pseudomonas, Staphylococcus spp., and actinobacterial
      strain with white aerial mycelium. The thermotolerant actinobacterial strain of
      the same morphology was repeatedly isolated from many locations in MCF: air,
      compost sample, and solid surface in production hall. On the base of complex
      morphological, chemotaxonomic, and phylogenetic characteristics, the isolate has
      been classified as Nocardiopsis alba. Dominant position of N. alba in microbial
      environment of the mushroom compost facility may represent an indicator
      microorganism in compost bioaerosol. The bioavailability of N. alba in mushroom
      compost facility creates potential risk for the health of workers, and the
      protection of respiratory tract and/or skin is strongly recommended.

PMID- 25382929
TI  - Radial line-scans as representative sampling strategy in dried-droplet laser
      ablation of liquid samples deposited on pre-cut filter paper disks.
AB  - Nebulising liquid samples and using the aerosol thus obtained for further
      analysis is the standard method in many current analytical techniques, also with
      inductively coupled plasma (ICP)-based devices. With such a set-up,
      quantification via external calibration is usually straightforward for samples
      with aqueous or close-to-aqueous matrix composition. However, there is a variety
      of more complex samples. Such samples can be found in medical, biological,
      technological and industrial contexts and can range from body fluids, like blood
      or urine, to fuel additives or fermentation broths. Specialized nebulizer systems
      or careful digestion and dilution are required to tackle such demanding sample
      matrices. One alternative approach is to convert the liquid into a dried solid
      and to use laser ablation for sample introduction. Up to now, this approach
      required the application of internal standards or matrix-adjusted calibration due
      to matrix effects. In this contribution, we show a way to circumvent these matrix
      effects while using simple external calibration for quantification. The principle
      of representative sampling that we propose uses radial line-scans across the
      dried residue. This compensates for centro-symmetric inhomogeneities typically
      observed in dried spots. The effectiveness of the proposed sampling strategy is
      exemplified via the determination of phosphorus in biochemical fermentation
      media. However, the universal viability of the presented measurement protocol is
      postulated. Detection limits using laser ablation-ICP-optical emission
      spectrometry were in the order of 40 MUg mL- 1 with a reproducibility of 10 %
      relative standard deviation (n = 4, concentration = 10 times the quantification
      limit). The reported sensitivity is fit-for-purpose in the biochemical context
      described here, but could be improved using ICP-mass spectrometry, if future
      analytical tasks would require it. Trueness of the proposed method was
      investigated by cross-validation with conventional liquid measurements, and by
      analyzing IAEA-153 reference material (Trace Elements in Milk Powder); a good
      agreement with the certified value for phosphorus was obtained.

PMID- 25382930
TI  - Synthesis of an Aminooxy Derivative of the Trisaccharide Globotriose Gb3.
AB  - The synthesis of alpha-aminooxy trisaccharide moiety [alpha-d-Gal-(1,4)-beta-d
      Gal-(1,4)-beta-d-Glc-alpha-aminooxy], related to the cell surface
      globotriaosylceramide (Gb3) receptor of the B subunit of the AB5 Shiga toxin of
      Shigella dysenteriae, has been synthesized for the first time in 11 steps with a
      15% overall isolated yield. A highlight of this work entails utilizing chemically
      compatible synthetic transformations, including those related to glycosylation,
      incorporative of the succinimidyl moiety as a precursor to the aminooxy Gb3
      derivative. The fully deprotected trisaccharide aminooxy compound was reacted
      with a carbonyl compound leading to oxime formation in quantitative yield
      underscoring the importance for future glyco-conjugations.

PMID- 25382931
TI  - Noise Induced Pattern Switching in Randomly Distributed Delayed Swarms.
AB  - We study the effects of noise on the dynamics of a system of coupled self
      propelling particles in the case where the coupling is time-delayed, and the
      delays are discrete and randomly generated. Previous work has demonstrated that
      the stability of a class of emerging patterns depends upon all moments of the
      time delay distribution, and predicts their bifurcation parameter ranges. Near
      the bifurcations of these patterns, noise may induce a transition from one type
      of pattern to another. We study the onset of these noise-induced swarm re
      organizations by numerically simulating the system over a range of noise
      intensities and for various distributions of the delays. Interestingly, there is
      a critical noise threshold above which the system is forced to transition from a
      less organized state to a more organized one. We explore this phenomenon by
      quantifying this critical noise threshold, and note that transition time between
      states varies as a function of both the noise intensity and delay distribution.

PMID- 25382932
TI  - Immediate Effects of a Program to Promote School Readiness in Low-Income
      Children: Results of a Pilot Study.
AB  - Children from low-income backgrounds demonstrate poorer school readiness skills
      than their higher-income peers. The Kids in Transition to School (KITS) Program
      was developed to increase early literacy, social skills, and self-regulatory
      skills among children with inadequate school readiness. In the present study, 39
      families participated in a pilot efficacy trial conducted through a community
      collaboration to examine the feasibility and impact of the KITS program with
      families from disadvantaged neighborhoods. Participating families were
      demographically representative of the larger populations in the participating
      school districts. Children who received the intervention demonstrated
      significantly greater improvements in letter naming, initial sound fluency, and
      understanding of concepts about print than their peers who did not participate in
      the intervention, as well as decreases in aggressive responses to peer
      provocation and increases in self-regulation skills. Results suggest that a
      brief, focused school readiness intervention is feasible to conduct with low
      income families and may improve critical skills.

PMID- 25382933
TI  - Effect of silicic acid on arsenate and arsenite retention mechanisms on 6-L
      ferrihydrite: A spectroscopic and batch adsorption approach.
AB  - The competitive adsorption of arsenate and arsenite with silicic acid at the
      ferrihydrite-water interface was investigated over a wide pH range using batch
      sorption experiments, attenuated total reflectance Fourier transform infrared
      (ATR-FTIR) spectroscopy, extended X-ray absorption fine structure (EXAFS)
      spectroscopy, and density functional theory (DFT) modeling. Batch sorption
      results indicate that the adsorption of arsenate and arsenite on the 6-L
      ferrihydrite surface exhibits a strong pH-dependence, and the effect of pH on
      arsenic sorption differs between arsenate and arsenite. Arsenate adsorption
      decreases consistently with increasing pH; whereas arsenite adsorption initially
      increases with pH to a sorption maximum at pH 7-9, where after sorption decreases
      with further increases in pH. Results indicate that competitive adsorption
      between silicic acid and arsenate is negligible under the experimental
      conditions; whereas strong competitive adsorption was observed between silicic
      acid and arsenite, particularly at low and high pH. In-situ, flow-through ATR
      FTIR data reveal that in the absence of silicic acid, arsenate forms inner
      sphere, binuclear bidentate, complexes at the ferrihydrite surface across the
      entire pH range. Silicic acid also forms inner-sphere complexes at ferrihydrite
      surfaces throughout the entire pH range probed by this study (pH 2.8 - 9.0). The
      ATR-FTIR data also reveal that silicic acid undergoes polymerization at the
      ferrihydrite surface under the environmentally-relevant concentrations studied
      (e.g., 1.0 mM). According to ATR-FTIR data, arsenate complexation mode was not
      affected by the presence of silicic acid. EXAFS analyses and DFT modeling
      confirmed that arsenate tetrahedra were bonded to Fe metal centers via binuclear
      bidentate complexation with average As(V)-Fe bond distance of 3.27 A. The EXAFS
      data indicate that arsenite forms both mononuclear bidentate and binuclear
      bidentate complexes with 6-L ferrihydrite as indicated by two As(III)-Fe bond
      distances of ~2.92-2.94 and 3.41-3.44 A, respectively. The As-Fe bond distances
      in both arsenate and arsenite EXAFS spectra remained unchanged in the presence of
      Si, suggesting that whereas Si diminishes arsenite adsorption preferentially, it
      has a negligible effect on As-Fe bonding mechanisms.

PMID- 25382934
TI  - Sapropterin Dihydrochloride Mixed With Common Foods and Beverages.
AB  - Sapropterin dihydrochloride is used to lower blood phenylalanine levels in
      tetrahydrobiopterin-responsive phenylketonuria in conjunction with a
      phenylalanine-restricted diet. This study investigated the solubility and
      stability of sapropterin tablets and a sapropterin powder formulation when mixed
      in selected beverages and foods. Solubility was partial for the tablets and
      complete for the powder. The stability testing showed that 93% or more of active
      sapropterin dihydrochloride is present at 1 hour after either tablets or powders
      are mixed with certain foods and beverages. Mixing sapropterin powder with foods
      and beverages might facilitate its administration in patients who have difficulty
      swallowing the drug according to prescribing information.

PMID- 25382935
TI  - Fully Automated Assessment of the Severity of Parkinson's Disease from Speech.
AB  - For several decades now, there has been sporadic interest in automatically
      characterizing the speech impairment due to Parkinson's disease (PD). Most early
      studies were confined to quantifying a few speech features that were easy to
      compute. More recent studies have adopted a machine learning approach where a
      large number of potential features are extracted and the models are learned
      automatically from the data. In the same vein, here we characterize the disease
      using a relatively large cohort of 168 subjects, collected from multiple (three)
      clinics. We elicited speech using three tasks - the sustained phonation task, the
      diadochokinetic task and a reading task, all within a time budget of 4 minutes,
      prompted by a portable device. From these recordings, we extracted 1582 features
      for each subject using openSMILE, a standard feature extraction tool. We compared
      the effectiveness of three strategies for learning a regularized regression and
      find that ridge regression performs better than lasso and support vector
      regression for our task. We refine the feature extraction to capture pitch
      related cues, including jitter and shimmer, more accurately using a time-varying
      harmonic model of speech. Our results show that the severity of the disease can
      be inferred from speech with a mean absolute error of about 5.5, explaining 61%
      of the variance and consistently well-above chance across all clinics. Of the
      three speech elicitation tasks, we find that the reading task is significantly
      better at capturing cues than diadochokinetic or sustained phonation task. In
      all, we have demonstrated that the data collection and inference can be fully
      automated, and the results show that speech-based assessment has promising
      practical application in PD. The techniques reported here are more widely
      applicable to other paralinguistic tasks in clinical domain.

PMID- 25382936
TI  - Acoustic and Lexical Representations for Affect Prediction in Spontaneous
      Conversations.
AB  - In this article we investigate what representations of acoustics and word usage
      are most suitable for predicting dimensions of affect|AROUSAL, VALANCE, POWER and
      EXPECTANCY|in spontaneous interactions. Our experiments are based on the AVEC
      2012 challenge dataset. For lexical representations, we compare corpus
      independent features based on psychological word norms of emotional dimensions,
      as well as corpus-dependent representations. We find that corpus-dependent bag of
      words approach with mutual information between word and emotion dimensions is by
      far the best representation. For the analysis of acoustics, we zero in on the
      question of granularity. We confirm on our corpus that utterance-level features
      are more predictive than word-level features. Further, we study more detailed
      representations in which the utterance is divided into regions of interest (ROI),
      each with separate representation. We introduce two ROI representations, which
      significantly outperform less informed approaches. In addition we show that
      acoustic models of emotion can be improved considerably by taking into account
      annotator agreement and training the model on smaller but reliable dataset.
      Finally we discuss the potential for improving prediction by combining the
      lexical and acoustic modalities. Simple fusion methods do not lead to consistent
      improvements over lexical classifiers alone but improve over acoustic models.

PMID- 25382937
TI  - Mental and Social Health Impacts the Use of Protective Behavioral Strategies in
      Reducing Risky Drinking and Alcohol Consequences.
AB  - The present study is the first to examine the moderating effects of mental and
      social health status in the relationship between protective behavioral strategies
      utilized to reduce high-risk drinking (e.g., alternating alcoholic and
      nonalcoholic drinks or avoiding drinking games) and alcohol outcomes (drinking
      variables and alcohol-related negative consequences) among first-year college
      females (N = 128). Findings revealed that protective behaviors were particularly
      effective in reducing both alcohol consumption and related risks among
      participants reporting lower mental health as compared to higher mental health.
      Further, participants with higher social health who utilized protective behaviors
      consumed significantly fewer maximum drinks per occasion than did peers who also
      employed protective behaviors but reported lower social health. Explanation of
      findings and implications for campus intervention initiatives are discussed.

PMID- 25382938
TI  - Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide)  nanoparticles
      for   the local delivery of cholecalciferol.
AB  - Cholecalciferol, vitamin D3, plays an important role in bonemetabolism by
      regulating extracellular levels of calcium. Presented here is a study on the
      effects of the local delivery of cholecalciferol (D3) using nanoparticulate
      carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide)
      (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the
      purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and
      (b) the secondary, osteoconductive and defect-filling effect of the carrier
      itself. Two types of HAp-based powders with particles of narrowly dispersed sizes
      in the nano range were prepared and tested in this study: HAp nanoparticles as
      direct cholecalciferol delivery agents and HAp nanoparticles coated with
      cholecalciferol-loaded poly(D,L)-lactide-co-glycolide (HAp/D3/PLGA). Satisfying
      biocompatibility of particulate systems, when incubated in contact with MC3T3-E1
      osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In
      contrast, an extensively fast release of cholecalciferol from the system
      comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered
      necrosis of the osteoblastic cells in vitro. Artificial defects induced in the
      osteoporotic bone of the rat mandible were successfully reconstructed following
      implantation of cholecalciferol-coated HAp nanoparticles as well as those
      comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA
      (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization,
      osteogenesis and bone structure differentiation were achieved upon the
      implementation of HAp/D3/PLGA systems.

PMID- 25382939
TI  - Controlling Enantioselectivity in Additions to Cyclic Oxocarbenium Ions via
      Transition Metal Catalysis.
AB  - Controlling enantioselectivity in additions to oxocarbenium ions remains a
      challenge in asymmetric catalysis. By catalytically generating a chiral
      organometallic intermediate, a copper acetylide, we have developed a novel
      approach for additions of carbon nucleophiles to cyclic oxocarbenium ions in high
      enantioselectivities and yields.

PMID- 25382940
TI  - 2,3-Butanedione monoxime increases sensitivity to Nikkomycin Z in the budding
      yeast Saccharomyces cerevisiae.
AB  - Nikkomycin Z (NZ) is a competitive inhibitor of chitin synthase III in the yeast
      Saccharomyces cerevisiae. Myosin type II-deficient yeast strains (myo1) display a
      dramatic reduction in growth when chitin synthase III activity is inhibited by
      NZ, supporting the contention that actomyosin motility plays an important role in
      maintaining cell wall integrity. A proposed inhibitor of cortical actin
      polymerization in vitro, 2,3-butanedione monoxime (BDM), also inhibits growth of
      wild-type yeast strains at a concentration of 20 mM. In this study, we assayed
      for potential in vivo interplay between BDM-sensitive cell functions and cell
      wall chitin synthesis by testing for increased sensitivity to NZ during co
      treatment with BDM at sub-inhibitory concentrations. Our results show that BDM
      can increase the sensitivity of yeast cells to Nikkomycin Z.

PMID- 25382941
TI  - Approach and Positive Affect in Toddlerhood Predict Early Childhood Behavior
      Problems.
AB  - The aim of the study was to examine the moderating role of positive affect on the
      relation between approach behaviors and adjustment outcomes. One hundred eleven
      toddlers participated in a laboratory assessment of approach and positive affect
      at 24 months. Behavior problems were reported by a parent in the fall of the
      child's kindergarten year. Results supported our hypotheses that children who
      displayed high approach and high positive affect in both non-threat and low
      threat contexts were rated as higher in externalizing behavior problems. On the
      other hand, for children showing low positive affect, increases in approach in a
      moderate threat context lowered the risk of developing internalizing behavior
      problems. Implications for these findings are discussed including methodological
      considerations of differences among eliciting contexts and advantages of
      separating positive affect and approach.

PMID- 25382943
TI  - Why are there different age relations in cross-sectional and longitudinal
      comparisons of cognitive functioning?
AB  - A major challenge for researchers interested in investigating relations between
      aging and cognitive functioning is distinguishing influences of aging from other
      determinants of cognitive performance. For example, cross-sectional comparisons
      may be distorted because people of different ages were born and grew up in
      different time periods, and longitudinal comparisons may be distorted because
      performance on a second occasion is influenced by the experience of performing
      the tests on the first occasion. One way in which these different types of
      influences might be investigated is with research designs involving comparisons
      of people of different ages from the same birth cohorts who are all tested for
      the first time in different years. Results from several recent studies using
      these types of designs suggest that the age trends in some cognitive abilities
      more closely resemble those from cross-sectional comparisons than those from
      longitudinal comparisons. These findings imply that a major reason for different
      age trends in longitudinal and cross-sectional comparisons of cognitive
      functioning is that the prior experience with the tests inflates scores on the
      second occasion in longitudinal studies.

PMID- 25382942
TI  - Development and validation of protein microarray technology for simultaneous
      inflammatory mediator detection in human sera.
AB  - Biomarkers, including cytokines, can help in the diagnosis, prognosis, and
      prediction of treatment response across a wide range of disease settings.
      Consequently, the recent emergence of protein microarray technology, which is
      able to quantify a range of inflammatory mediators in a large number of samples
      simultaneously, has become highly desirable. However, the cost of commercial
      systems remains somewhat prohibitive. Here we show the development, validation,
      and implementation of an in-house microarray platform which enables the
      simultaneous quantitative analysis of multiple protein biomarkers. The accuracy
      and precision of the in-house microarray system were investigated according to
      the Food and Drug Administration (FDA) guidelines for pharmacokinetic assay
      validation. The assay fell within these limits for all but the very low-abundant
      cytokines, such as interleukin- (IL-) 10. Additionally, there were no significant
      differences between cytokine detection using our microarray system and the "gold
      standard" ELISA format. Crucially, future biomarker detection need not be limited
      to the 16 cytokines shown here but could be expanded as required. In conclusion,
      we detail a bespoke protein microarray system, utilizing well-validated ELISA
      reagents, that allows accurate, precise, and reproducible multiplexed biomarker
      quantification, comparable with commercial ELISA, and allowing customization
      beyond that of similar commercial microarrays. 

PMID- 25382944
TI  - Selective decision-making deficit in love following damage to the anterior
      insula.
AB  - Neuroimaging studies have found a correlation between activation in the anterior
      insula and love, and a correlation between activation in the posterior insula and
      lust. The present control-case study describes a neurological male patient, with
      a rare, circumscribed lesion in the anterior insula, whom we tested using a
      decision task that required he judge whether each of a series of attractive
      individuals could be the object of his love or lust. The patient, in contrast
      with neurologically typical participants matched on age, gender, and ethnicity,
      performed normally when making decisions about lust but showed a selective
      deficit when making decisions about love. These results provide the first
      clinical evidence indicating that the anterior insula may play an instrumental
      role in love but not lust more generally. These data support the notion of a
      posterior-to-anterior insular gradient, from sensorimotor to abstract
      representations, in the evaluation of anticipatory rewards in interpersonal
      relationships.

PMID- 25382945
TI  - Metallurgical characterization of experimental Ag-based soldering alloys.
AB  - AIM: To characterize microstructure, hardness and thermal properties of
      experimental Ag-based soldering alloys for dental applications. MATERIALS AND
      METHODS: Ag12Ga (AgGa) and Ag10Ga5Sn (AgGaSn) were fabricated by induction
      melting. Six samples were prepared for each alloy and microstructure, hardness
      and their melting range were determined by, scanning electron microscopy, energy
      dispersive X-ray (EDX) microanalysis, X-ray diffraction (XRD), Vickers hardness
      testing and differential scanning calorimetry (DSC). RESULTS: Both alloys
      demonstrated a gross dendritic microstructure while according to XRD results both
      materials consisted predominately of a Ag-rich face centered cubic phase The
      hardness of AgGa (61 +/- 2) was statistically lower than that of AgGaSn (84 +/-
      2) while the alloys tested showed similar melting range of 627-762  degrees C for
      AgGa and 631-756  degrees C for AgGaSn. CONCLUSION: The experimental alloys
      tested demonstrated similar microstructures and melting ranges. Ga and Sn might
      be used as alternative to Cu and Zn to modify the selected properties of Ag based
      soldering alloys.

PMID- 25382946
TI  - Subjective image quality comparison between two digital dental radiographic
      systems and conventional dental film.
AB  - OBJECTIVES: Digital radiography has become an integral part of dentistry. Digital
      radiography does not require film or dark rooms, reduces X-ray doses, and
      instantly generates images. The aim of our study was to compare the subjective
      image quality of two digital dental radiographic systems with conventional dental
      film. MATERIALS & METHODS: A direct digital (DD) 'Digital' system by Sirona, a
      semi-direct (SD) digital system by Vista-scan, and Kodak 'E' speed dental X-ray
      films were selected for the study. Endodontically-treated extracted teeth (n =
      25) were used in the study. Details of enamel, dentin, dentino-enamel junction,
      root canal filling (gutta percha), and simulated apical pathology were
      investigated with the three radiographic systems. The data were subjected to
      statistical analyzes to reveal differences in subjective image quality. RESULTS:
      Conventional dental X-ray film was superior to the digital systems. For digital
      systems, DD imaging was superior to SD imaging. CONCLUSION: Conventional film
      yielded superior image quality that was statistically significant in almost all
      aspects of comparison. Conventional film was followed in image quality by DD, and
      SD provided the lowest quality images. Conventional film is still considered the
      gold standard to diagnose diseases affecting the jawbone. RECOMMENDATIONS:
      Improved software and hardware for digital imaging systems are now available and
      these improvements may now yield images that are comparable in quality to
      conventional film. However, we recommend that studies still use more observers
      and other statistical methods to produce ideal results.

PMID- 25382947
TI  - Influence of extended light exposure curing times on the degree of conversion of
      resin-based pit and fissure sealant materials.
AB  - PURPOSE: The aim of present study was to evaluate extended curing times on the
      degree of conversion (DC) of filled and unfilled resin-based materials used as
      pit and fissure sealants. MATERIALS AND METHODS: The materials examined were a
      flowable composite (FiltekTM Z350 XT Flowable) and a pit and fissure sealant
      (ClinproTM Sealant). Thirty disks of each material were prepared. The 30 made of
      the flowable composite were divided into three groups (n = 10 each) according to
      the three different curing times studied: 20 s (group 1), 40 s (group 2), and 60
      s (group 3). Similarly, the 30 disks made of the pit and fissure sealant were
      divided into three groups (n = 10 each) according to the three different curing
      times: 20 s (group 4), 40 s (group 5), and 60 s (group 6). After polymerization,
      the disks were removed from the mold and stored in dry, lightproof containers in
      an incubator at 37  degrees C for 24 h. The DC was obtained using an Avatar 320
      FTIR spectrometer. Then the data were analyzed using the Kruskal-Wallis test and
      the Fisher's least significant difference post hoc test for multiple comparisons
      (alpha = 0.05). RESULTS: DC values for the flowable composite (FiltekTM Z350 XT)
      were higher (p = 0.002) than those for the pit and fissure sealant (ClinproTM
      Sealant). Group 2 and group 5 showed significantly higher DC values than group 1
      and group 4, respectively. There was no difference between groups 2 and 3 or
      between groups 5 and 6 (p = 2.93). CONCLUSION: An extended curing time improves
      the DC to some extent for both materials.

PMID- 25382948
TI  - Agreement between orthodontist and patient perception using Index of Orthodontic
      Treatment Need.
AB  - OBJECTIVES: The primary objective of the study was to assess the agreement
      between orthodontist and patient perception regarding the Aesthetic Component of
      the Index of Orthodontic Treatment Need (IOTN-AC) at pre-orthodontic treatment
      levels. The secondary objective was to determine how well the subjective
      assessment of malocclusion (IOTN-AC) correlated with the normative Dental Health
      Component of the IOTN (IOTN-DC). MATERIALS AND METHODS: A cross-sectional
      analytical study was conducted on patients between the ages of 16 and 25,
      presenting for initiation of orthodontic treatment with no history of prior
      orthodontic treatment. The mean age of the total sample population was 19.50 +/-
      3.15 years. The mean age of the males was 19.05 +/- 3.09 years and for females it
      was 19.75 +/- 3.18 years. The sample consisted of 41 males and 80 females.
      Patients were shown their pretreatment monochrome intraoral frontal photographs
      to rate according to the IOTN-AC. Simultaneously, the orthodontist reviewed the
      photographs with each patient. The IOTN-DHC of pretreatment casts was also
      recorded by the orthodontist. The frequency of specific traits that had led to
      increased severity of malocclusion was also identified. All readings were
      recorded manually on a data collection form. The data were assessed using the chi
      square test, Spearman's correlation and Cohen's kappa test. Intra- and inter
      examiner reliability was assessed using Spearman's correlation. RESULTS: A
      significant positive relationship (p < 0.05) was observed between orthodontist
      and patient perception (r = 0.516), orthodontist perception and the normative
      need (r = 0.430), and between the patient perception and the normative need (r =
      0.252). A statistically significant level of agreement was observed between
      orthodontist and patient perception (kappa = 0.339, p ? 0.001, 95% CI, 0.207
      0.470) and between orthodontist perception and the normative need (kappa = 0.331,
      p ? 0.001, 95% CI, 0.197-0.424). A weak and insignificant level of agreement was
      observed between patient perception and normative treatment need (kappa = 0.107,
      95% CI, 0.02-0.187). CONCLUSIONS: Patient understanding of their treatment need
      or aesthetic classification may not always be as accurate as that of
      orthodontists. This may be a cause for concern when an orthodontist finds a
      certain condition to be severe, and a patient who does not agree may limit their
      treatment needs.

PMID- 25382949
TI  - The effects of light curing units and environmental temperatures on C
      000000000000 000000000000 000000000000 111111111111 000000000000 111111111111
      000000000000 000000000000 000000000000 C conversion of commercial and
      experimental bonding agents.
AB  - BACKGROUND AND PURPOSE: Polymerization of bonding agents (BA) is a critical
      factor in determining the success of bonded restorations. We aimed to assess the
      effects of two light curing units and two temperatures on the extent of
      polymerization (EP) of a commercial BA and an experimental BA. METHODS: Forty BA
      specimens were randomly divided into 8 subgroups of n = 5 to compare the
      polymerization of two BAs (experimental/Scotchbond) based on the variables:
      temperature (23/37  degrees C) and light-curing unit (quartz-tungsten
      halogen/light-emitting diode). The EP (%) was measured using differential
      scanning calorimetry, and analyzed using the t-test, two- and three-way analyses
      of variance (ANOVA), and the Bonferroni test (alpha = 0.05). RESULTS: There were
      significant differences between the EP results between the two BAs (P = 0.012)
      and due to the different temperatures (P = 0.001), but not between the different
      light-curing units (P = 0.548). The interaction between BA and temperature was
      significant (P < 0.001). The other interactions were nonsignificant. CONCLUSIONS:
      The two light-curing units had similar effects on the EP. The EP values were
      better when curing was performed at human body temperature.

PMID- 25382950
TI  - Influence of phase I periodontal therapy on levels of matrix metalloproteinase 1
      and tissue inhibitor of metalloproteinase 1.
AB  - BACKGROUND: Matrix metalloproteinase-1 (MMP-1) is a member of a family of enzymes
      that can degrade most extracellular matrix macromolecules. Extracellularly, MMPs
      are controlled by tissue inhibitors of metalloproteinases (TIMPs) and by
      mechanisms of pro-MMP activation. Levels of MMPs and TIMPs change during healing,
      inflammation, and normal tissue turnover. Herein we aimed to evaluate the levels
      of MMP-1 and TIMP-1 in gingival crevicular fluid (GCF) from periodontally healthy
      patients (control group) and chronic periodontitis patients before and after
      phase 1 therapy. METHODS: In this study we examined 30 patients who had chronic
      periodontitis with probing depth sites ?5 mm and a clinical attachment level
      (CAL) ?5 mm. We included 30 periodontally healthy patients as a control. Clinical
      measurements such as plaque (PI) and gingival (GI) indices, papillary bleeding
      index (PBI), probing depths (PD), and CAL were recorded both before treatment
      (BT) and after phase I periodontal treatment (AT). Assays for MMP-1 and TIMP-1
      were performed with an enzyme-linked immunosorbent assay (ELISA) method. RESULTS:
      All clinical parameters were significantly reduced at the post-therapy visit. MMP
      1 levels were significantly higher in patients BT than the controls; however, the
      patients AT were not statistically different than the controls. TIMP-1 levels in
      patients BT were significantly lower than in the controls and significantly lower
      than patients AT. We observed a significant positive correlation between GCF
      volume and MMP-1 levels. Furthermore, TIMP-1 levels were significantly negatively
      correlated with both GCF volume and all clinical parameters. CONCLUSIONS: We
      observed that as the extent of periodontal destruction increases, MMP-1
      concentration increases and TIMP-1 concentration decreases in GCF. When chronic
      periodontitis patients were treated by scaling and root planing (SRP), the
      average MMP-1 concentrations decreased and TIMP-1 concentrations increased in
      GCF.

PMID- 25382951
TI  - Cheiloscopy and blood groups: Aid in forensic identification.
AB  - INTRODUCTION: Every person has certain features that make them radically distinct
      from others. One such feature is lip prints. Lip prints remain the same
      throughout life and are uninfluenced by injuries, diseases, or environmental
      changes. Different individuals have specific blood groups according to the
      various antigen-antibody reactions in their bloodstream. AIM: To determine the
      distribution of different patterns of lip prints among subjects having different
      ABO and Rh blood groups. OBJECTIVE: To determine the correlation between
      respective characteristics of subjects. METHODOLOGY: In this study, lip prints
      were obtained from 122 subjects (62 males and 60 females), and associated blood
      group matching was performed to determine the predominant lip print type and to
      determine any correlation between lip print types and blood groups. Tsuchihashi's
      classification of type I (complete vertical grooves), type I' (incomplete
      vertical grooves), type II (forking grooves), type III (intersecting grooves),
      type IV (reticular grooves), and type V (indeterminate grooves) was used to
      compare with the ABO and Rh blood grouping systems. RESULT: No correlation was
      found between lip prints and blood groups. CONCLUSION: No significant correlation
      exists between blood group and lip prints. Lip prints play a vital role in
      identification because they are unique.

PMID- 25382952
TI  - Intraoral management of displaced root into submandibular space under local
      anaesthesia -A case report and review of literature.
AB  - Accidental displacement of an impacted third molar, either a root fragment,
      crown, or the entire tooth, is a rare complication that occurs during exodontia.
      The most common sites of dislodgment of an impacted mandibular third molar
      fragment are the sublingual, submandibular, and pterygomandibular spaces. Removal
      of a displaced root tip from these spaces may be complex due to poor
      visualization and limited access. A thorough evaluation of all significant risk
      factors must be performed in advance to prevent complications. This paper reports
      the case of a patient who presented with a mandibular third molar root that was
      displaced into submandibular space. The case was managed intraorally under local
      anaesthesia and review of the literature. 

PMID- 25382953
TI  - ANALYSIS OF DEPENDENTLY CENSORED DATA BASED ON QUANTILE REGRESSION.
AB  - Dependent censoring occurs in many biomedical studies and poses considerable
      methodological challenges for survival analysis. In this work, we develop a new
      approach for analyzing dependently censored data by adopting quantile regression
      models. We formulate covariate effects on the quantiles of the marginal
      distribution of the event time of interest. Such a modeling strategy can
      accommodate a more dynamic relationship between covariates and survival time
      compared to traditional regression models in survival analysis, which usually
      assume constant covariate effects. We propose estimation and inference
      procedures, along with an efficient and stable algorithm. We establish the
      uniform consistency and weak convergence of the resulting estimators. Extensive
      simulation studies demonstrate good finite-sample performance of the proposed
      inferential procedures. We illustrate the practical utility of our method via an
      application to a multicenter clinical trial that compared warfarin and aspirin in
      treating symptomatic intracranial arterial stenosis.

PMID- 25382954
TI  - Continuous K-Nearest Neighbor Processing Based on Speed and Direction of Moving
      Objects in a Road Network.
AB  - Recent research has focused on Continuous K-Nearest Neighbor (CKNN) query over
      moving objects in road networks. A CKNN query is to find among all moving objects
      the K-Nearest Neighbors (KNNs) of a moving query point within a given time
      interval. As the data objects move frequently and arbitrarily in road networks,
      the frequent updates of object locations make it complicated to process CKNN
      accurately and efficiently. In this paper, according to the relative moving
      situation between the moving objects and the query point, a Moving State of
      Object (MSO) model is presented to indicate the relative moving state of the
      object to the query point. With the help of this model, we propose a novel Object
      Candidate Processing (OCP) algorithm to highly reduce the repetitive query cost
      with pruning phase and refining phase. In the pruning phase, the data objects
      which cannot be the KNN query results are excluded within the given time
      interval. In the refining phase, the time subintervals of the given time interval
      are determined where the certain KNN query results are obtained. Comprehensive
      experiments are conducted and the results verify the effectiveness of the
      proposed methods.

PMID- 25382955
TI  - Collaboration With Urban Parents to Deliver a Community-Based Youth HIV
      Prevention Program.
AB  - This article draws on the unified theory of behavior change to examine adult
      community members' participation in a collaborative, community-based HIV
      prevention program for inner-city youth. Specifically, the impact of a training
      and mentorship process is examined with a sample of parent facilitators hired to
      deliver an evidence-based HIV prevention program in Bronx, New York. Findings
      indicate that the training program impacted four of five key constructs
      (environmental constraints, habitual behavior, social norms, and self-concept)
      expected to be related to parents' ability to deliver the program constructs
      significantly beyond any increase evidenced by the control group (HIV knowledge
      increased in both groups). Community-level training programs may therefore be an
      effective medium for increasing caregivers' intention to collaborate in community
      based prevention programs.

PMID- 25382956
TI  - Machine Learning in Medical Imaging.

PMID- 25382957
TI  - Positive Semidefinite Rank-based Correlation Matrix Estimation with Application
      to Semiparametric Graph Estimation.
AB  - Many statistical methods gain robustness and flexibility by sacrificing
      convenient computational structures. In this paper, we illustrate this
      fundamental tradeoff by studying a semi-parametric graph estimation problem in
      high dimensions. We explain how novel computational techniques help to solve this
      type of problem. In particular, we propose a nonparanormal neighborhood pursuit
      algorithm to estimate high dimensional semiparametric graphical models with
      theoretical guarantees. Moreover, we provide an alternative view to analyze the
      tradeoff between computational efficiency and statistical error under a smoothing
      optimization framework. Though this paper focuses on the problem of graph
      estimation, the proposed methodology is widely applicable to other problems with
      similar structures. We also report thorough experimental results on text, stock,
      and genomic datasets.

PMID- 25382958
TI  - Sparsity Inducing Prior Distributions for Correlation Matrices of Longitudinal
      Data.
AB  - For longitudinal data, the modeling of a correlation matrix R can be a difficult
      statistical task due to both the positive definite and the unit diagonal
      constraints. Because the number of parameters increases quadratically in the
      dimension, it is often useful to consider a sparse parameterization. We introduce
      a pair of prior distributions on the set of correlation matrices for longitudinal
      data through the partial autocorrelations (PACs), each of which vary
      independently over [-1,1]. The first prior shrinks each of the PACs toward zero
      with increasingly aggressive shrinkage in lag. The second prior (a selection
      prior) is a mixture of a zero point mass and a continuous component for each PAC,
      allowing for a sparse representation. The structure implied under our priors is
      readily interpretable for time-ordered responses because each zero PAC implies a
      conditional independence relationship in the distribution of the data. Selection
      priors on the PACs provide a computationally attractive alternative to selection
      on the elements of R or R-1 for ordered data. These priors allow for data
      dependent shrinkage/selection under an intuitive parameterization in an
      unconstrained setting. The proposed priors are compared to standard methods
      through a simulation study and a multivariate probit data example. Supplemental
      materials for this article (appendix, data, and R code) are available online.

PMID- 25382959
TI  - The Development and Evaluation of a Parent Empowerment Program for Family Peer
      Advocates.
AB  - Family-to-family services are emerging as an important adjunctive service to
      traditional mental health care and a vehicle for improving parent engagement and
      service use in children's mental health services. In New York State, a growing
      workforce of Family Peer Advocates (FPA) is delivering family-to-family services.
      We describe the development and evaluation of a professional program to enhance
      Family Peer Advocate professional skills, called the Parent Engagement and
      Empowerment Program (PEP). We detail the history and content of PEP and provide
      data from a pre/post and 6-month follow up evaluation of 58 FPA who participated
      in the first Statewide regional training effort. Self-efficacy, empowerment, and
      skills development were assessed at 3 time points: baseline, post-training, and 6
      month follow-up. The largest changes were in self-efficacy and empowerment.
      Regional differences suggest differences in Family Peer Advocate workforce across
      areas of the state. This evaluation also provides the first systematic
      documentation of Family Peer Advocate activities over a six-month period.
      Consistent with peer specialists within the adult health care field, FPA in the
      children's mental health field primarily focused on providing emotional support
      and service access issues. Implications for expanding family-to-family services
      and integrating it more broadly into provider organizations are described.

PMID- 25382960
TI  - Impact of Brief Intervention Services on Drug Using Truant Youth Arrest Charges
      over Time.
AB  - School truancy is a serious concern in the U.S., with far-reaching negative
      consequences. Truancy has been positively associated with substance use and
      delinquent behavior; however, research is limited. Consequently, the Truancy
      Brief Intervention Project was established to treat and prevent substance use and
      other risky behaviors among truants. This article examines whether the Brief
      Intervention program is more effective in preventing future delinquency over a 12
      month follow-up period, than the standard truancy program. Results indicate the
      Brief Intervention was marginally significant in effecting future delinquency
      among truants, compared to the standard truancy program. Future implications of
      this study are discussed.

PMID- 25382961
TI  - Using Task Analytic Models and Phenotypes of Erroneous Human Behavior to Discover
      System Failures Using Model Checking.
AB  - Breakdowns in complex systems often occur as a result of system elements
      interacting in ways unanticipated by analysts or designers. In systems with human
      operators, human-automation interaction associated with both normative and
      erroneous human behavior can contribute to such failures. This paper presents a
      method for automatically generating task analytic models encompassing both
      erroneous and normative human behavior from normative task models. The resulting
      model can be integrated into a formal system model so that system safety
      properties can be formally verified with a model checker. This allows analysts to
      prove that a human automation-interactive system (as represented by the model)
      will or will not satisfy safety properties with both normative and generated
      erroneous human behavior. This method is illustrated with a case study: the
      operation of a radiation therapy machine. In this example, a problem resulting
      from a generated erroneous human action is discovered. Future extensions of our
      method are discussed.

PMID- 25382963
TI  - Show Me, Don't Tell Me: Behavioral Rehearsal as a Training and Analogue Fidelity
      Tool.
AB  - Behavioral rehearsal, when a trainee engages in a simulated interaction with
      another individual, is an underutilized but potentially cost-effective and
      feasible solution for two difficult questions in implementation science: how to
      improve training, a commonly used implementation strategy, and how to feasibly
      measure fidelity using analogue methods in community settings. This paper
      provides practical information on how to develop and use behavioral rehearsal for
      both of these purposes to implementation researchers. Therefore, we focus on
      development and use of behavioral rehearsal as a training and analogue fidelity
      tool in the context of three illustrative studies.

PMID- 25382962
TI  - Trajectories of Depressive Symptoms in Women Prior to and for Six Months After
      Breast Cancer Surgery.
AB  - Depressive symptoms are common in women with breast cancer. This study evaluated
      how ratings of depressive symptoms changed from the time of the preoperative
      assessment to 6 months after surgery and investigated whether specific
      demographic, clinical, and symptom characteristics predicted preoperative levels
      of and/or characteristics of the trajectories of depressive symptoms.
      Characteristics that predicted higher preoperative levels of depressive symptoms
      included being married/partnered; receipt of adjuvant chemotherapy; more fear of
      metastasis; higher levels of trait anxiety, state anxiety, sleep disturbance,
      problems with changes in appetite; more hours per day in pain; and lower levels
      of attentional function. Future studies need to evaluate associations between
      anxiety, fears of recurrence, and uncertainty, as well as personality
      characteristics and depressive symptoms.

PMID- 25382964
TI  - Suicidal Ideation Associated with PCL Checklist-Ascertained PTSD among Veterans
      Treated for Substance Abuse.
AB  - This manuscript begins by reviewing the literature concerning the use of the SCID
      versus the PCL for diagnosing PTSD, and by reviewing the literature regarding the
      presence of suicidal ideation as a clinical correlate of PTSD. This manuscript
      then describes our recent study involving PTSD among Veterans, which assessed the
      presence of suicidal ideation as a clinical correlate of PTSD, as diagnosed by
      the SCID versus as diagnosed by the PCL. We hypothesized that the presence of
      suicidal ideation would be associated with a diagnosis of PTSD. Subjects were 101
      Veterans recruited from VA behavioral health and substance use treatment clinics
      in the VA Pittsburgh Healthcare System. The study compared correlations of
      suicidal ideation with PTSD as determined with the PTSD Checklist versus the
      Structured Clinical Interview for DSM-IV, and utilized question 9 of the Beck
      Depression Inventory for assessing presence of SI. PTSD was diagnosed in 15
      subjects using the SCID, and in 15 subjects using the PTSD Checklist. SI were
      reported by 16 subjects. The presence of SI was significantly associated with the
      diagnosis of PTSD on the PCL (chi-square=5.73, df=1, p=0.017) but not on the SCID
      (chi-square=0.08, df=1, p=0.773). These findings suggest that SI associated with
      the diagnosis of PTSD among Veterans are better ascertained by the PCL as
      compared to the more elaborate diagnostic algorithm used in the SCID. The current
      study finding raises the possibility that a less complicated diagnostic
      assessment instrument such as the PCL may be superior to the SCID, a more
      complicated instrument for diagnosing PTSD, at least in some populations.

PMID- 25382965
TI  - Structural characterization of the MU-Nitrido Complex {[Fe(OEP)]2N}
AB  - The molecular structure of the MU-nitrido dimer, MU-nitrido-bis(2,3,7,8,12,13,
      17,18-octaethylporphyrinato)iron, is reported. The axial Fe-N distances average
      to 1.657 (11) A and the equatorial distances average to 2.005(5) A. Although not
      required by symmetry, the two iron centers appear equivalent and are consistent
      with an assignment of a low-spin state and a formal oxidation state of +3.5. A
      comparison of this structure with other nitrido-bridged species is given.

PMID- 25382966
TI  - Trauma Exposures and Posttraumatic Stress among Zimbabwean refugees in South
      Africa.
AB  - Zimbabwean refugees can be considered a vulnerable group in terms of how they are
      displaced with many of them having lived through hardships on their way to South
      Africa and other African countries. Zimbabwe is known to be Africa's most
      extraordinary producer of migrants and the biggest producer of refugees in
      Southern Africa. It is estimated that 3.4 million Zimbabweans, a quarter of the
      country's population, have fled the country. Economic collapse, hunger and
      political repression have been blamed for the mass exodus. The present study
      examines the impact of trauma exposures (pre- and post-migration stressors and
      poor mental health) on posttraumatic stress disorder (PTSD) among homeless
      Zimbabwean refugees living in South Africa. Through a guided convenient sampling,
      in-depth interviews using questionnaires were collected from 125 homeless
      Zimbabwean refugees in Polokwane, Limpopo Province, South Africa. The study was
      anchored on the hypothesis that predictor variables (pre- and post- migration
      stressors, poor mental health) would significantly affect outcomes (PTSD).
      Participants were assessed on demographic variables, pre- and post-migration
      difficulties checklists, mental health using the General Health Questionnaire
      (GHQ-28) and the PTSD Checklist (Civilian Version (PCL). Participants ranged from
      18 to 48 years with a mean age of 28.3 years (SD = 6.27). The majority of the
      sample had at least a secondary education (76.8%) and were employed as unskilled
      labourers (61.6%) in South Africa. Being married was reported by 54.4% in
      Zimbabwe but changed to only 19.2% in South Africa. Hierarchical multiple
      regression analyses showed that the overall model significantly predicted PTSD
      among homeless Zimbabweans (R2 = 0.17, adjusted R2 = 0.11, F (6, 124) = 2.960, p
      < .01). Thus, the entire set of pre- and post-migration variables (Post total
      stress, PreThreat to life, Presexabuse, PrePoverty, Postsexabuse, Postpoverty and
      two mental health symptoms (Anxiety and Insomnia, and Social dysfunction)
      explained 41.2 % of the total variance on PTSD. However, main significant
      predictors were Post total stress (t (125) = 2.571, P < .001); Postsexabuse (t
      (125) = 2.175, P < .003); Postpoverty (t (125) = 3.450, P < .001); Anxiety and
      Insomnia (t (125) = 2.000, P < .04) and Social dysfunction (t (125) = 2.113, P <
      .003). Of these variables in order of strong impact predictor is Post total
      stress (beta = 0.737) followed by Postpoverty (beta = 0.701), Postsexabuse (beta
      = 0.377) and Social dysfunction (beta = 0.196). The Dubin-Watson results (2.252)
      also showed that the assumption of independent errors was tenable and almost
      certainly met for this model. Variables excluded in the model were Pre total
      Stress, Post threat to life, Somatic complaints (GHQ A), Severe depression (GHQ
      D) and Total GHQ. Zimbabwean refugees constitute a particularly vulnerable group
      to poor mental health and PTSD. These findings have significant implications for
      refugees in South Africa and other places where integrating refugee treament in
      the main stream health system is undermined. As a migratory group, there is need
      to develop ways of using probability sampling methods in further research and
      increasing sample size. In addition, there is need to develop culturally relevant
      interventions to address the sequalaes of pre- and post-migration traumas and
      poor mental health.

PMID- 25382967
TI  - Influence of the prediction error of the first eye undergoing cataract surgery on
      the refractive outcome of the fellow eye.
AB  - INTRODUCTION: In addition to measurement errors, individual anatomical conditions
      could be made responsible for unexpected prediction errors in the determination
      of the correct intraocular lens power for cataract surgery. Obviously, such
      anatomical conditions might be relevant for both eyes. The purpose of this study
      was to evaluate whether the postoperative refractive error of the first eye has
      to be taken in account for the biometry of the second. METHODS: In this
      retrospective study, we included 670 eyes of 335 patients who underwent
      phacoemulsification and implantation of a foldable intraocular lens in both eyes.
      According to the SRK/T formula, the postoperative refractive error of each eye
      was determined and compared with its fellow eye. RESULTS: Of 670 eyes, 622 showed
      a postoperative refractive error within +/-1.0 D (93%), whereas the prediction
      error was 0.5 D or less in 491 eyes (73%). The postoperative difference between
      both eyes was within 0.5 D in 71% and within 1.0 D in 93% of the eyes. Comparing
      the prediction error of an eye and its fellow eye, the error of the fellow eye
      was about half the value of the other. CONCLUSION: Our results imply that
      substitution of half of the prediction error of the first eye into the
      calculation of the second eye may be useful to reduce the prediction error in the
      second eye. However, prospective studies should be initiated to demonstrate an
      improved accuracy for the second eye's intraocular lens power calculation by
      partial adjustment.

PMID- 25382968
TI  - Endophthalmitis following pars plana vitrectomy: a literature review of
      incidence, causative organisms, and treatment outcomes.
AB  - Endophthalmitis following pars plana vitrectomy is a very uncommon cause of
      endophthalmitis. Cases reported over the last decade show a decrease in incidence
      over time. To optimize visual outcome, early diagnosis and treatment are
      essential. In this review we report a summary of the incidence of endophthalmitis
      following vitrectomy, various risk factors for their occurrence, the
      microbiological profile and the visual outcomes post treatment. 

PMID- 25382969
TI  - The diurnal and nocturnal effects of travoprost in normal-tension glaucoma.
AB  - PURPOSE: To determine the diurnal and nocturnal effects of travoprost with
      sofZia((r)) (Travatan Z((r)) [TZ]) on intraocular pressure (IOP) and ocular
      perfusion pressure (OPP) in patients with normal-tension glaucoma (NTG). METHODS:
      Twenty-seven subjects with NTG were admitted to an inpatient sleep laboratory for
      three 24-hour sessions monitoring IOP, blood pressure (BP), and heart rate every
      2 hours in the habitual position (diurnal period: upright; nocturnal period:
      supine). Baseline IOP and OPP levels were compared to those during active
      treatment with TZ and 3 days after stopping the medication. OPP was calculated as
      2/3 [diastolic BP + 1/3 (systolic BP - diastolic BP)] - IOP. RESULTS: TZ
      significantly reduced the mean diurnal and nocturnal IOP levels compared to
      baseline at all time points. During treatment, mean IOP decreased from 17.1+/-3.4
      to 14.7+/-3.0 mmHg during the diurnal period (P<0.01) and from 19.9+/-3.6 to
      18.8+/-3.5 mmHg during the nocturnal period (P<0.01). Once treatment was
      discontinued, mean IOP remained at levels significantly less than baseline during
      both the diurnal (15.6+/-3.2 mmHg) and nocturnal (18.7+/-3.7 mmHg) periods. Mean
      OPP was not significantly changed with treatment during either period.
      CONCLUSION: In this population of NTG patients, TZ significantly lowers IOP at
      all time points throughout the diurnal and nocturnal periods. The treatment
      effect on IOP endures for up to 3 days after the last dose. Treatment did not
      significantly improve OPP.

PMID- 25382970
TI  - Curcumin could reduce the monomer of TTR with Tyr114Cys mutation via autophagy in
      cell model of familial amyloid polyneuropathy.
AB  - Transthyretin (TTR) familial amyloid polyneuropathy (FAP) is an autosomal
      dominant inherited neurodegenerative disorder caused by various mutations in the
      transthyretin gene. We aimed to identify the mechanisms underlying TTR FAP with
      Tyr114Cys (Y114C) mutation. Our study showed that TTR Y114C mutation led to an
      increase in monomeric TTR and impaired autophagy. Treatment with curcumin
      resulted in a significant decrease of monomeric TTR by recovering autophagy. Our
      research suggests that impairment of autophagy might be involved in the
      pathogenesis of TTR FAP with Y114C mutation, and curcumin might be a potential
      therapeutic approach for TTR FAP. 

PMID- 25382972
TI  - Patient experience and use of probiotics in community-based health care settings.
AB  - OBJECTIVE: To investigate patient experience with probiotics and factors that
      influence probiotic use among adult patients. METHOD: Patients were invited to
      complete a questionnaire that assessed their experiences and opinions regarding
      probiotics. Questionnaires were distributed to patients seeking primary health
      care services at a family and community medicine practice site and a community
      pharmacy. Patients were invited to complete the questionnaire while awaiting the
      physician or waiting for prescriptions to be filled. RESULTS: Overall, 162
      surveys were completed and returned (66% response rate) from patients aged 18 to
      89 years of age (mean 49.5 years). Most patients (n=107; 65%) were familiar with
      the term "probiotic", and 49 patients (29.9%) had personally used the supplements
      in the past. Of those who had used probiotics, the majority (57%) had used the
      supplements to maintain "good gastrointestinal health" and most (59%) felt that
      the supplements had been beneficial. However, most (59%) had not informed their
      health care provider about their use of the supplements. CONCLUSION: Use of
      probiotic supplements is common among consumers, but may not be reported to
      health care providers.

PMID- 25382971
TI  - Clinicopathological significance and potential drug target of p15INK4B in
      multiple myeloma.
AB  - Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation
      of malignant plasma cells in the bone marrow and the production of monoclonal
      immunoglobulin. In addition to genetic changes, gene hypermethylation is an
      alternative mechanism of tumor suppressor gene inactivation in MM. The cyclin
      dependent kinase inhibitor 1 (CDKN2B or p15(INK4B) ) gene lies adjacent to the
      tumor suppressor gene, cyclin-dependent kinase inhibitor 2 (CDKN2A), and is
      frequently mutated and deleted in a wide variety of tumors, including MM.
      However, there is a lack of systematic analysis of p15 epigenetic modification
      such as methylation in MM from different studies that can provide more powerful
      estimation of an effect. In this study, we have systematically reviewed the
      studies of p15(INK4B) promoter methylation in MM and quantified the association
      between p15(INK4B) promoter methylation and MM using meta-analysis methods. We
      observed that the frequency of p15(INK4B) methylation is significantly higher in
      MM patients than in normal healthy controls. The pooled odds ratio (OR) from ten
      studies including 394 MM and 99 normal individuals is 0.08, while confidence
      interval (CI) is 0.03-0.21 (P<0.00001). This indicates that p15(INK4B)
      inactivation through methylation plays an important role in the pathogenesis of
      MM. In addition, the frequency of p15(INK4B) methylation was significantly higher
      in patients with MM than in those with asymptomatic monoclonal gammopathy of
      undetermined significance. The pooled OR from four studies is 0.40, 95% CI =0.21
      0.78 (P=0.007). These results suggest that silencing of p15(INK4B) gene
      expression by epigenetic modification such as promoter hypermethylation plays a
      role not only in the initiation of MM but also in plasma cell malignant
      transformation, disease progression, and development. 

PMID- 25382973
TI  - Cross-cultural adaptation and reliability testing of Polish adaptation of the
      European Heart Failure Self-care Behavior Scale (EHFScBS).
AB  - BACKGROUND: Development of simple instruments for determination of self-care
      levels in heart failure (HF) patients is a subject of ongoing research. One such
      instrument, gaining growing popularity worldwide, is the European Heart Failure
      Self-care Behavior Scale (EHFScBS). The aim of this study was to adapt and to
      test reliability of the Polish version of EHFScBS. METHOD: A standard guideline
      was used for translation and cultural adaptation of the English version of
      EHFScBS into Polish. The study included 100 Polish HF patients aged between 24
      and 91 years, among them 67 men and 33 women. Cronbach's alpha was used for
      analysis of the internal consistency of EHFScBS. RESULTS: Mean total self-care
      score in the study group was 34.2+/-8.1 points. Good or satisfactory level of
      self-care were documented in four out of 12 analyzed EHFScBS domains. Cronbach's
      alpha for the entire questionnaire was 0.64. The value of Cronbach's alpha after
      deletion of specific items ranged from 0.55 to 0.65. CONCLUSION: Polish HF
      patients present significant deficits of self-care, which are to a large extent
      associated with inefficacy of the public health care system. Apart from cultural
      characteristics, the socioeconomic context of the target population should be
      considered during language adaptation of EHFScBS, as well as during
      interpretation of data obtained with this instrument. A number of self-care
      related behaviors may be optimized as a result of appropriate educational
      activities, also those offered by nursing personnel.

PMID- 25382974
TI  - Effectiveness of a life story work program on older adults with intellectual
      disabilities.
AB  - OBJECTIVE: This study examines the effectiveness of a life story work program
      (LSWp) in older adults with mild-to-moderate levels of intellectual disability
      (ID). METHODS: Using a quasiexperimental design, this study assigned 60 older
      adults who were between 50-90 years old with mild-to-moderate levels of ID to
      receive either the LSWp (intervention group, N=32) or usual activities (control
      group, N=28) during a period of 6 months. Evaluation was made based on the
      outcomes assessed by the Mood Interest and Pleasure Questionnaire, the Vineland
      Adaptive Behavior Scales, and the Personal Wellbeing Index - ID. RESULTS AND
      CONCLUSION: LSWp shows potential for improving the quality of life and preventing
      the loss of interest and pleasure in older adults with ID. It also shows promise
      in enhancing their socialization skills. Patients with better communication
      abilities seemed to benefit more from the LSWp.

PMID- 25382975
TI  - Synthesis and characterization of bioactive conjugated near-infrared fluorescent
      proteinoid-poly(L-lactic acid) hollow nanoparticles for optical detection of
      colon cancer.
AB  - Colon cancer is one of the major causes of death in the Western world. Early
      detection significantly improves long-term survival for patients with colon
      cancer. Near-infrared (NIR) fluorescent nanoparticles are promising candidates
      for use as contrast agents for tumor detection. Using NIR offers several
      advantages for bioimaging compared with fluorescence in the visible spectrum:
      lower autofluorescence of biological tissues and lower absorbance and,
      consequently, deeper penetration into biomatrices. The present study describes
      the preparation of new NIR fluorescent proteinoid-poly(L-lactic acid) (PLLA)
      nanoparticles. For this purpose, a P(EF-PLLA) random copolymer was prepared by
      thermal copolymerization of L-glutamic acid (E) with L-phenylalanine (F) and
      PLLA. Under suitable conditions, this proteinoid-PLLA copolymer can self-assemble
      to nanosized hollow particles of relatively narrow size distribution. This self
      assembly process was used for encapsulation of the NIR dye indocyanine green. The
      encapsulation process increases significantly the photostability of the dye.
      These NIR fluorescent nanoparticles were found to be stable and nontoxic. Leakage
      of the NIR dye from these nanoparticles into phosphate-buffered saline containing
      4% human serum albumin was not detected. Tumor-targeting ligands such as peanut
      agglutinin and anticarcinoembryonic antigen antibodies were covalently conjugated
      to the surface of the NIR fluorescent P(EF-PLLA) nanoparticles, thereby
      increasing the fluorescent signal of tumors with upregulated corresponding
      receptors. Specific colon tumor detection by the NIR fluorescent P(EF-PLLA)
      nanoparticles was demonstrated in a chicken embryo model. In future work, we plan
      to extend this study to a mouse model, as well as to encapsulate a cancer drug
      such as doxorubicin within these nanoparticles for therapeutic applications. 

PMID- 25382977
TI  - Microwave-assisted polyol synthesis of carbon nitride dots from folic acid for
      cell imaging.
AB  - A green, one-step microwave-assisted polyol synthesis was employed to prepare
      blue luminescent carbon nitride dots (CNDs) using folic acid molecules as both
      carbon and nitrogen sources. The as-prepared CNDs had an average size of around
      4.51 nm and could be well dispersed in water. Under excitation at 360 nm, the
      CNDs exhibited a strong blue luminescence and the quantum yield was estimated to
      be 18.9%, which is greater than that of other reported CNDs. Moreover, the CNDs
      showed low cytotoxicity and could efficiently label C6 glioma cells,
      demonstrating their potential in cell imaging. 

PMID- 25382976
TI  - Clavanin bacterial sepsis control using a novel methacrylate nanocarrier.
AB  - Controlling human pathogenic bacteria is a worldwide problem due to increasing
      bacterial resistance. This has prompted a number of studies investigating
      peptides isolated from marine animals as a possible alternative for control of
      human pathogen infections. Clavanins are antimicrobial peptides isolated from the
      marine tunicate Styela clava, showing 23 amino acid residues in length, cationic
      properties, and also high bactericidal activity. In spite of clear benefits from
      the use of peptides, currently 95% of peptide properties have limited
      pharmaceutical applicability, such as low solubility and short half-life in the
      circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in
      order to develop nanoantibiotics against bacterial sepsis. Clavanin was
      nanostructured using EUDRAGIT((r)) L 100-55 and RS 30 D solution (3:1 w:w).
      Atomic force, scanning electron microscopy and dynamic light scattering showed
      nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of 
      7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was
      assessed by reversed-phase chromatography. In vitro bioassays showed that the
      nanostructured clavanin was partially able to control development of
      Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
      Furthermore, nanostructures did not show hemolytic activity. In vivo sepsis
      bioassays were performed using C57BL6 mice strain inoculated with a polymicrobial
      suspension. Assays led to 100% survival rate under sub-lethal sepsis assays and
      40% under lethal sepsis assays in the presence of nanoformulated clavanin A until
      the seventh day of the experiment. Data here reported indicated that
      nanostructured clavanin A form shows improved antimicrobial activity and has the
      potential to be used to treat polymicrobial infections. 

PMID- 25382978
TI  - Magnetic seizure therapy in an adolescent with refractory bipolar depression: a
      case report.
AB  - Magnetic seizure therapy (MST) has shown efficacy in adult patients with
      treatment-resistant depression with limited impairment in memory. To date, the
      use of MST in adolescent depression has not been reported. Here we describe the
      first successful use of MST in the treatment of an adolescent patient with
      refractory bipolar depression. This patient received MST in an ongoing open-label
      study for treatment-resistant major depression. Treatments employed a twin-coil
      MST apparatus, with the center of each coil placed over the frontal cortex (ie,
      each coil centered over F3 and F4). MST was applied at 100 Hz and 100% machine
      output at progressively increasing train durations. Depressive symptoms were
      assessed using the 24-item Hamilton Depression Rating Scale and cognitive
      function was assessed with a comprehensive neuropsychological battery. This
      adolescent patient achieved full remission of clinical symptoms after an acute
      course of 18 MST treatments and had no apparent cognitive decline, other than
      some autobiographical memory impairment that may or may not be related to the MST
      treatment. This case report suggests that MST may be a safe and well tolerated
      intervention for adolescents with treatment-resistant bipolar depression. Pilot
      studies to further evaluate the effectiveness and safety of MST in adolescents
      warrant consideration. 

PMID- 25382979
TI  - Managing cardiovascular disease risk in patients treated with antipsychotics: a
      multidisciplinary approach.
AB  - BACKGROUND: The use of antipsychotic medication in the United States and
      throughout the world has greatly increased over the last fifteen years. These
      drugs have significant side effect burdens, many of them relating to
      cardiovascular health. OBJECTIVE: To review the available evidence on the major
      cardiovascular issues that arise in patients taking antipsychotic medication.
      METHOD: A PubMed literature review was performed to identify recent meta
      analyses, review articles, and large studies. Further articles were identified
      through cited papers and based on expert consultation when necessary. RESULTS:
      CLINICAL GUIDANCE ON THE FOLLOWING ADVERSE EFFECTS AND ANTIPSYCHOTICS WAS
      REVIEWED: electrocardiogram (ECG) changes, (specifically, prolonged QT and risk
      of torsades de pointes), weight gain, dyslipidemia, metabolic syndrome, and
      myocarditis. Specific attention was paid to monitoring guidelines and treatment
      options in the event of adverse events, including dose change, medication switch,
      or adjuvant therapy.

PMID- 25382980
TI  - Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC.
AB  - Aberrant methylation of CpG dinucleotides is a commonly observed epigenetic
      modification in human cancer. Thus, detection of aberrant gene promoter
      methylation as a tool for diagnosis of tumors or as a prognostic marker has been
      widely described for many types of cancers, including nonsmall cell lung cancer
      (NSCLC). Emerging evidence indicates that CDH13 is a candidate tumor suppressor
      in several types of human tumors, including NSCLC. However, the correlation
      between CDH13 hypermethylation and clinicopathological characteristics of NSCLC
      remains unclear. In the current study, we conducted a systematic review and meta
      analysis to quantitatively evaluate the effects of CDH13 hypermethylation on the
      incidence of NSCLC and clinicopathological characteristics. Final analysis of 803
      NSCLC patients from eleven eligible studies was performed. CDH13 hypermethylation
      was observed to be significantly higher in NSCLC than in normal lung tissue, with
      the pooled odds ratio (OR) from seven studies including 448 NSCLC and 345 normal
      lung tissue (OR, 7.85; 95% confidence interval, 5.12-12.03; P<0.00001). CDH13
      hypermethylation was also associated with pathological types. The pooled OR was
      obtained from four studies, including 111 squamous cell carcinoma and 106
      adenocarcinoma (OR, 0.35; 95% confidence interval, 0.19-0.66; P=0.001), which
      indicated that CDH13 hypermethylation plays a more important role in the
      pathogenesis of adenocarcinoma. NSCLC with CDH13 hypermethylation was found more
      frequently in poorly differentiated NSCLC patients. NSCLC patients with CDH13
      hypermethylation had a lower survival rate than those without CDH13
      hypermethylation. In addition, CDH13 mRNA high expression was found to correlate
      with better overall survival for all NSCLC patients followed for 20 years (hazard
      ratio, 0.81; P=0.0056). Interestingly, CDH13 mRNA overexpression was found to
      correlate with better overall survival only in adenocarcinoma patients (hazard
      ratio, 0.42; P=9.6e-09), not in squamous cell carcinoma patients (hazard ratio,
      0.93; P=0.59). The results of this meta-analysis suggest that CDH13
      hypermethylation is associated with an increased risk and worse survival in
      NSCLC. CDH13 hypermethylation and mRNA expression play an important role in
      carcinogenesis, progression, and development, as well as clinical outcomes. 

PMID- 25382981
TI  - Independent and combined effect of diet and exercise in adults with prediabetes.
AB  - Prediabetes is defined as impaired fasting glucose and/or impaired glucose
      tolerance. Impaired fasting glucose is usually defined as fasting blood glucose
      between 5.6 mmol/L and 6.9 mmol/L (100.8-124.2 mg/dL), and impaired glucose
      tolerance is the 2-hour oral glucose tolerance test of 7.8-11.0 mmol/L (140.4
      198.0 mg/dL). Most individuals with prediabetes are overweight or obese and are
      at greater risk of type 2 diabetes (T2D). The first line of treatment for
      individuals with prediabetes is lifestyle modification, including diet and
      exercise. The aim of this review, through the revision of primarily randomized
      control trials, is to discuss the independent and combined effect of diet and
      exercise on the incidence of T2D, glycemic control, and weight loss in adults
      with prediabetes. Based on the available literature, lifestyle modification
      combining both diet and exercise is effective at reducing the incidence of T2D
      and improving glycemic control, even without a significant reduction in body
      weight. Thus, it is unclear whether weight loss, through lifestyle modification,
      is a cornerstone for improving glycemic control in individuals with prediabetes.
      The independent effect of diet or exercise alone on the improvement in glycemic
      control and/or reduction in body weight in individuals with prediabetes still
      requires more studies to draw a clear conclusion, considering the quality and
      quantity of available studies. As of now, the best diet and/or exercise program
      to improve glycemic control and body weight in adults with prediabetes is
      unknown. 

PMID- 25382982
TI  - Clinical utility of pharmacogenomics in the management of hepatitis C.
AB  - Hepatitis C virus (HCV) was identified for the first time more than 20 years ago.
      Since then, several studies have highlighted the complicated aspects of this
      viral infection in relation to its worldwide prevalence, its clinical
      presentation, and its therapeutic response. Recently, two landmark scientific
      breakthroughs have moved us closer to the successful eradication of chronic HCV
      infection. First, response rates in treatment-naive patients and in prior non
      responders to pegylated-interferon-alpha and ribavirin therapy are increasing as
      a direct consequence of the development of direct-acting antiviral drugs.
      Secondly, the discovery of single-nucleotide polymorphisms near the interleukin
      28B gene significantly related to spontaneous and treatment-induced HCV clearance
      represents a milestone in the HCV therapeutic landscape. The implementation of
      this pharmacogenomics finding as a routine test for HCV-infected patients has
      enhanced our understanding of viral pathogenesis, has encouraged the design of
      ground-breaking antiviral treatment regimens, and has become useful for
      pretreatment decision making. Nowadays, interleukin 28B genotyping is considered
      to be a key diagnostic tool for the management of HCV-infected patients and will
      maintain its significance for new combination treatment schemes using direct
      acting antiviral agents and even in interferon-free regimens. Such
      pharmacogenomics insights represent a challenge to clinicians, researchers, and
      health administrators to transform this information into knowledge with the aim
      of elaborating safer and more effective therapeutic strategies specifically
      designed for each patient. In conclusion, the individualization of treatment
      regimens for patients with hepatitis C, that may lead to a universal cure in
      future years, is becoming a reality due to recent developments in biomarker and
      genomic medicine. In light of these advances, we review the scientific evidence
      and clinical implications of recent findings related to host genetic factors in
      the management of HCV infection. 

PMID- 25382983
TI  - Some mechanisms of the protective effect of ischemic preconditioning on rat liver
      ischemia-reperfusion injury.
AB  - Ischemia-reperfusion (I/R) injury is a multifactorial process that affects graft
      function after liver transplantation. An understanding of the mechanisms involved
      in I/R injury is essential for the design of therapeutic strategies to improve
      the outcome of liver transplantation. The generation of reactive oxygen species
      subsequent to reoxygenation inflicts tissue damage and initiates a cascade of
      deleterious cellular responses, leading to inflammation, cell death, and ultimate
      organ failure. Increasing experimental evidence has suggested that Kupffer cells
      and T-cells mediate activation of neutrophil inflammatory responses. Activated
      neutrophils infiltrate the injured liver in parallel with increased expression of
      adhesion molecules on endothelial cells. The heme oxygenase system is among the
      most critical of the cytoprotective mechanisms activated during cellular stress,
      exerting antioxidant and anti-inflammatory functions, modulating the cell cycle,
      and maintaining the microcirculation. Finally, the activation of toll-like
      receptors on Kupffer cells may play a fundamental role in exploring new
      therapeutic strategies based on the concept that hepatic I/R injury represents a
      case for host "innate" immunity. In the present study, there was a significant
      decrease in hepatic activity of glycogen in the I/R group as compared with
      corresponding values in the control group. On the other hand, there was a
      significant increase in the hepatic activity of glycogen in the I/R-IP (ischemic
      preconditioning) group as compared with corresponding values in the I/R group. 

PMID- 25382984
TI  - Observational study of upper gastrointestinal tract bleeding events in patients
      taking duloxetine and nonsteroidal anti-inflammatory drugs: a case-control
      analysis.
AB  - PURPOSE: To determine whether the concomitant use of duloxetine with prescription
      nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin was associated with an
      increased risk for upper gastrointestinal (UGI) bleeding compared with taking
      these analgesics alone. METHODS: Truven Health Analytics MarketScan Research
      Databases were examined for hospital admissions of adult patients indexed from
      January 1, 2007-December 31, 2011. Cases were patients with UGI hemorrhage or
      peptic ulcer disease. Controls were randomly selected from the remaining
      admissions to match 10:1 with cases based on age, sex, and admission date.
      Prescription medication exposure groups of interest were: 1) no exposure to
      duloxetine, NSAIDs or aspirin; 2) duloxetine only; 3) NSAIDs or aspirin only; 4)
      duloxetine plus NSAIDs or aspirin. Logistic regression and relative excess risk
      due to interaction was utilized to estimate any increased risk of UGI bleeding
      for patients prescribed these medications across these groups. RESULTS: There
      were 33,571 cases and 335,710 controls identified. Comparing exposure group 2 and
      group 4, the adjusted odds ratio was 1.03 (95% confidence interval [CI], 0.94,
      1.12), and the adjusted relative excess risk due to interaction was 0.352 (95%
      CI: -0.18, 0.72) for risk of UGI bleeding, neither of which support an increased
      risk or an interaction between duloxetine and prescription NSAID or aspirin for
      these events. CONCLUSION: There was no evidence of an increased risk for UGI
      bleeding when duloxetine was taken with prescription NSAIDs or aspirin. In
      addition, there was no evidence of an interaction between duloxetine and
      prescription NSAIDs or aspirin for an increased risk of these events.

PMID- 25382985
TI  - Recurrent myocardial infarctions in a young football player secondary to
      thrombophilia, associated with elevated factor VIII activity.
AB  - Myocardial infarction (MI) due to coronary atherosclerosis in young adults is
      uncommon; rare causes such as cocaine abuse, arterial dissection, and
      thromboembolism should be considered. A 21-year-old football player, and
      otherwise healthy African American man, developed chest pain during exercise
      while bench-pressing 400 lbs. Acute MI was diagnosed based on physical
      examination, electrocardiography findings, and elevated cardiac enzymes. Coronary
      arteriography showed a thrombus occluding the proximal left anterior descending
      artery (LAD). Aggressive antiplatelet therapy with aspirin, clopidogrel, and
      eptifibatide was pursued, in addition to standard post-MI care. This led to the
      successful resolution of symptoms and dissolution of the thrombus, demonstrated
      by repeat coronary arteriography. Five months later, he presented with similar
      symptoms during exercise after lifting heavy weights, and was found to have
      another acute MI. Coronary arteriography again showed a thrombus occluding the
      LAD. No evidence of coronary artery dissection or vasospasm was found. Only mild
      atherosclerotic plaque burden was observed on both occasions by intravascular
      ultrasound. A bare metal stent was placed at the site as it was thought this site
      had acted as a nidus for small plaque rupture and thrombus formation. Elevated
      serum factor VIII activity at 205% (reference range 60%-140%) was found, a rare
      cause of hypercoagulability. Further workup revealed a patent foramen ovale
      during a Valsalva maneuver by transesophageal echocardiography. Both events
      occurred during weight lifting, which can transiently increase right heart
      pressure in a similar way to the Valsalva maneuver. In light of all the findings,
      we concluded that an exercise-related increase in factor VIII activity led to
      coronary arterial thrombosis in the presence of a small ruptured plaque.
      Alternatively, venous clots may have traversed the patent foramen ovale and
      occluded the LAD. In addition to continuing aggressive risk factor modification,
      anticoagulation therapy with warfarin was initiated with close follow-up. 

PMID- 25382986
TI  - A common presentation to an uncommon disease. Penile Mondor's disease: a case
      report and literature review.
AB  - Penile Mondor's disease, or superficial thrombophlebitis of the dorsal vein of
      the penis, is a relatively uncommon but potentially anxiety-inducing self
      limiting condition that should be easily recognizable by any primary care
      practitioner. It typically presents with a cord-like mass and pain to the dorsal
      penis and has a myriad of causes, including trauma, excessive sexual activity,
      excessive exercise, or malignancy. Although Penile Mondor's disease is typically
      a clinical diagnosis, Doppler ultrasound is the initial imaging modality of
      choice if there is question or doubt about the diagnosis. Accurate diagnosis and
      reassurance about the condition's benign and self-limiting nature assuages most
      patients' fears. Treatment is primarily symptomatic but may vary depending on
      possible underlying disease processes. 

PMID- 25382987
TI  - Evaluating the effects of dexmedetomidine compared to propofol as adjunctive
      therapy in patients with alcohol withdrawal.
AB  - BACKGROUND: In severe alcohol withdrawal (AW), benzodiazepines may be inadequate
      to control symptoms. In many situations, benzodiazepine dosing escalates despite
      no additional efficacy and introduces potential toxicities. Severe cases of AW
      may require additional agents to control symptoms. Case reports and studies have
      shown benefits with dexmedetomidine and propofol in severe AW, but these agents
      have not been compared with one another. This study compares the effects of
      dexmedetomidine and propofol on benzodiazepine and haloperidol utilization in
      patients with AW. METHODS: A retrospective chart review was completed on 41
      patients with AW who received adjunctive dexmedetomidine or propofol. The primary
      objective was to compare benzodiazepine and haloperidol utilization before and
      after initiation of dexmedetomidine or propofol. Secondary measures included AW
      and sedation scoring, analgesic use, intensive care unit length of stay, rates of
      intubation, and adverse events. RESULTS: Among the dexmedetomidine and propofol
      groups, significant reductions in benzodiazepine (P<=0.0001 and P=0.043,
      respectively) and haloperidol (P<=0.0001 and P=0.026, respectively) requirements
      were observed. These reductions were comparable between groups (P=0.933 and
      P=0.465, respectively). A trend toward decreased intensive care unit length of
      stay in the dexmedetomidine group (123.6 hours vs 156.5 hours; P=0.125) was seen.
      Rates of intubation (14.7% vs 100%) and time of intubation (19.9 hours vs 97.6
      hours; P=0.002) were less in the dexmedetomidine group. Incidence of hypotension
      was 17.6% in the dexmedetomidine group vs 28.5% in the propofol group. Incidence
      of bradycardia was 17.6% in the dexmedetomidine group vs 0% in the propofol
      group. No differences were observed in other secondary outcomes. CONCLUSION: In
      patients with severe AW who require sedation, both dexmedetomidine and propofol
      have unique and advantageous properties. Both agents appear to have equivalent
      efficacy in reducing AW-related symptoms and benzodiazepine and haloperidol
      requirements. These results should be validated in a larger, prospective trial.

PMID- 25382988
TI  - Technical and radiological image quality comparison of different liquid crystal
      displays for radiology.
AB  - BACKGROUND: To inform cost-effective decisions in purchasing new medical liquid
      crystal displays, we compared the image quality in displays made by three
      manufacturers. METHODS: We recruited 19 radiologists and residents to compare the
      image quality of four liquid crystal displays, including 3-megapixel Barco((r)),
      Eizo((r)), and NEC((r)) displays and a 6-megapixel Barco display. The evaluators
      were blinded to the manufacturers' names. Technical assessments were based on
      acceptance criteria and test patterns proposed by the American Association of
      Physicists in Medicine. Radiological assessments were performed on images from
      the American Association of Physicists in Medicine Task Group 18. They included X
      ray images of the thorax, knee, and breast, a computed tomographic image of the
      thorax, and a magnetic resonance image of the brain. Image quality was scored on
      an analog scale (range 0-10). Statistical analysis was performed with repeated
      measures analysis of variance. RESULTS: The Barco 3-megapixel display passed all
      acceptance criteria. The Eizo and NEC displays passed the acceptance criteria,
      except for the darkest pixel value in the grayscale display function. The Barco 6
      megapixel display failed criteria for the maximum luminance response and the
      veiling glare. Mean radiological assessment scores were 7.8+/-1.1 (Barco 3
      megapixel), 7.8+/-1.2 (Eizo), 8.1+/-1.0 (NEC), and 8.1+/-1.0 (Barco 6-megapixel).
      No significant differences were found between displays. CONCLUSION: According to
      the tested criteria, all the displays had comparable image quality; however,
      there was a three-fold difference in price between the most and least expensive
      displays.

PMID- 25382991
TI  - Helping newcomers overcome barriers to health care.

PMID- 25382990
TI  - Sexual Partner Type Taxonomy Use Among Black Adolescent Mothers in the United
      States.
AB  - PURPOSE: Research on sexual-partner type focuses mostly on "main" and "casual"
      partner categories. The literature indicates that adolescent girls are less
      likely to use condoms with main partners, and more likely to use condoms with
      casual partners. Adolescent mothers may have different types of sexual partners
      than other adolescent girls. The purpose of this study was to explore and
      describe the range of male sexual partner types reported by Black adolescent
      mothers. DESIGN AND SAMPLE: This study was a qualitative description of the
      perspectives of Black, predominantly African-American, mothers (n=31). Data were
      generated using focus groups and interviews. The participants' ages ranged from
      15-19 years. MEASURES: A semi-structured qualitative questioning guide was used
      to stimulate focused discussions. Transcribed data were analyzed using
      qualitative content analysis. RESULTS: The range of sexual partner types of the
      women were reflected in three themes (1) All main partners are not created equal;
      (2) They're not casual partners because there are strings attached; (3) "Wham,
      bam, thank you ma'am:" No strings attached. Nine partner types were identified
      under these three themes, including a "baby daddy" partner. CONCLUSION: The
      partner-types of Black adolescent mothers are more robust than the "main" and
      "casual" partner categories typically referenced in the research literature. The
      range of sex partners includes the birth fathers of their children. Clinicians
      and researchers must consider how co-parenthood status is used in the
      construction of the "baby daddy" partner and what implications this unique sexual
      partner type may have on risk reduction behaviors such as condom use.

PMID- 25382989
TI  - Al-hijamah and oral honey for treating thalassemia, conditions of iron overload,
      and hyperferremia: toward improving the therapeutic outcomes.
AB  - Iron overload causes iron deposition and accumulation in the liver, heart, skin,
      and other tissues resulting in serious tissue damages. Significant blood
      clearance from iron and ferritin using wet cupping therapy (WCT) has been
      reported. WCT is an excretory form of treatment that needs more research efforts.
      WCT is an available, safe, simple, economic, and time-saving outpatient modality
      of treatment that has no serious side effects. There are no serious limitations
      or precautions to discontinue WCT. Interestingly, WCT has solid scientific and
      medical bases (Taibah mechanism) that explain its effectiveness in treating many
      disease conditions differing in etiology and pathogenesis. WCT utilizes an
      excretory physiological principle (pressure-dependent excretion) that resembles
      excretion through renal glomerular filtration and abscess evacuation. WCT
      exhibits a percutaneous excretory function that clears blood (through fenestrated
      skin capillaries) and interstitial fluids from pathological substances without
      adding a metabolic or detoxification burden on the liver and the kidneys.
      Interestingly, WCT was reported to decrease serum ferritin (circulating iron
      stores) significantly by about 22.25% in healthy subjects (in one session) and to
      decrease serum iron significantly to the level of causing iron deficiency (in
      multiple sessions). WCT was reported to clear blood significantly of
      triglycerides, low-density lipoprotein (LDL) cholesterol, total cholesterol, uric
      acid, inflammatory mediators, and immunoglobulin antibodies (rheumatoid factor).
      Moreover, WCT was reported to enhance the natural immunity, potentiate
      pharmacological treatments, and to treat many different disease conditions. There
      are two distinct methods of WCT: traditional WCT and Al-hijamah (WCT of prophetic
      medicine). Both start and end with skin sterilization. In traditional WCT, there
      are two steps, skin scarification followed by suction using plastic cups (double
      S technique); Al-hijamah is a three-step procedure that includes skin suction
      using cups, scarification (shartat mihjam in Arabic), and second skin suction
      (triple S technique). Al-hijamah is a more comprehensive technique and does
      better than traditional WCT, as Al-hijamah includes two pressure-dependent
      filtration steps versus one step in traditional WCT. Whenever blood plasma is to
      be cleared of an excess pathological substance, Al-hijamah is indicated. We will
      discuss here some reported hematological and therapeutic benefits of Al-hijamah,
      its medical bases, methodologies, precautions, side effects, contraindications,
      quantitative evaluation, malpractice, combination with oral honey treatment, and
      to what extent it may be helpful when treating thalassemia and other conditions
      of iron overload and hyperferremia. 

PMID- 25382992
TI  - Case 1: A premature infant with stridor.

PMID- 25382993
TI  - Case 2: A seven-year-old girl with diplopia.

PMID- 25382994
TI  - Discussing the need for an adolescent hepatitis B vaccine booster in infant
      vaccinees.

PMID- 25382995
TI  - Atypical antipsychotics for psychosis in adolescents.

PMID- 25382996
TI  - Paediatrician office follow-up of common minor fractures.
AB  - BACKGROUND: Evidence suggests that minor paediatric fractures can be followed by
      primary care paediatricians (PCPs). OBJECTIVES: To determine PCP opinions,
      knowledge and perceived barriers to managing minor paediatric fractures in the
      office. METHODS: An online survey was sent between June and September 2013 to all
      paediatricians who subscribed to the American Academy of Pediatrics PROS-Net
      Listerv and to those who were registered with the Scott's Canadian Medical
      Directory as paediatricians who treated children in a primary care capacity. The
      primary outcome was the proportion of PCPs who agreed with PCP follow-up of minor
      paediatric fractures. Secondary outcomes included PCP's perceived barriers to
      office follow-up. RESULTS: A total of 1752 surveys were sent; 1235 were eligible
      and 459 (37.2%) responded to the survey. Overall, 296 (69.5% [95% CI 65.2% to
      74.0%]) PCPs agreed that minor paediatric fractures could be followed in a PCP
      office. The most frequently reported barriers were lack of materials to replace
      immobilization (58.1%), PCP knowledge deficits (44.8%) and a perceived parental
      preference for an orthopedic surgeon (38.6%). Finally, 58.8% of respondents
      believed that further education was necessary if PCPs assumed responsibility for
      follow-up of midshaft clavicle fractures, while 66.5% and 77.1% (P<0.0001)
      believed this was necessary for distal radius buckle and fibular fractures,
      respectively. CONCLUSIONS: More than two-thirds of responding PCPs in Canada and
      the United States agreed that minor common paediatric fractures can be followed
      up by paediatricians. However, PCPs reported some barriers to this management
      strategy, including a desire for more education on this topic.

PMID- 25382997
TI  - Prevalence of malnutrition at the time of admission among patients admitted to a
      Canadian tertiary-care paediatric hospital.
AB  - BACKGROUND: Malnutrition among hospitalized children is known to negatively
      influence their response to therapy and to prolong their admission. It also has
      short- and long-term consequences for growth, development and well-being. It is
      commonly regarded as a condition affecting children in low-income countries;
      however, malnutrition has been found to be variably prevalent among hospitalized
      children in higher-income countries. At the time the present study was conducted,
      it had been >30 years since the nutritional status of Canadian hospitalized
      children was last published. OBJECTIVES: To determine and communicate the
      prevalence of malnutrition among children in a Canadian tertiary-care paediatric
      hospital at the time of their admission. METHODS: In the present cross-sectional
      study, anthropometric measures were obtained from 322 children admitted to The
      Hospital for Sick Children in Toronto, Ontario. Nutritional indexes (BMI for age,
      weight for age, weight for length/height and length/height for age) were
      generated from anthropometric measures using the WHO igrowup software, and
      summarized according to WHO definitions. RESULTS: The overall prevalence of
      malnutrition using BMI for age was 39.6% (95% CI 33% to 46%), of which 8.8% and
      30.8% of participants were under- and overnourished, respectively. Furthermore,
      6.9% (95% CI 3% to 13%) were determined to be acutely malnourished (weight for
      length/height <-2 SD) and 13.4% (95% CI 10% to 18%) chronically malnourished
      (length/height for age <-2 SD). CONCLUSION: The high prevalence of overall
      malnutrition observed among study participants suggests that initial screening
      using simple anthropometric measures should be conducted on hospital admission so
      that patients can receive appropriate nutrition-specific care.

PMID- 25382998
TI  - A comparison of the epidemiology of ice hockey injuries between male and female
      youth in Canada.
AB  - BACKGROUND: Hockey is played by youth across Canada, and its popularity has
      increased dramatically among females in the past decade. Despite this, there has
      been little epidemiological research comparing the injury patterns of young
      female and male hockey players. OBJECTIVE: To describe and compare injuries
      sustained by female and male youth hockey players using the Canadian Hospitals
      Injury Reporting and Prevention Program database. METHODS: In the present cross
      sectional, retrospective comparison study, the Canadian Hospitals Injury
      Reporting and Prevention Program database was used to identify all hockey-related
      injuries sustained by children seven to 17.5 years of age over a 15-year period
      (January 1995 to December 2009). Exclusion criteria included paid professional
      players and children with injuries sustained while playing road hockey. RESULTS:
      Inclusion criteria were met by 33,233 children (2637 [7.9%] females and 30,596
      [92.1%] males). Compared with males, females reported proportionately more soft
      tissue injuries (39.8% versus 32.6%; P<0.01) and sprains/strains (21.1% versus
      17.6%; P<0.01). Males experienced more fractures (27.1% versus 18.2%; P<0.01) and
      were most often injured through body checking (42.8% versus 25.7%; P<0.01).
      Females showed a trend toward increased concussion with age, and were most often
      injured through collisions (28.6% versus 24.6%; P<0.01). CONCLUSION: Compared
      with males, female hockey players sustained proportionately more soft tissue
      injures and sprains/strains, and showed a trend toward concussions in late
      adolecence. Males experienced more fractures, shoulder injuries and injuries due
      to body checking. Further research is required to identify risk factors for
      injury in female youth hockey players and to target injury prevention.

PMID- 25382999
TI  - Risk factors for positional plagiocephaly and appropriate time frames for
      prevention messaging.
AB  - OBJECTIVE: To determine potential risk factors for developing positional
      plagiocephaly in infants seven to 12 weeks of age in Calgary, Alberta. METHODS: A
      prospective cohort design was used. Healthy term infants (n=440), seven to 12
      weeks of age, from well-child clinics at four community health centres in
      Calgary, Alberta were assessed by the primary author and a registered nurse
      research assistant using Argenta's plagiocephaly assessment tool. Parents
      completed a questionnaire surveying risk factors. RESULTS: The incidence of
      positional plagiocephaly was estimated to be 46.6%. The following risk factors
      were identified using multiple logistic regression: right-sided head positional
      preference (OR 4.66 [95% CI 2.85 to 7.58]; P<0.001), left-sided head positional
      preference (OR 4.21 [95% CI 2.45 to 7.25]; P<0.001), supine sleep position (OR
      2.67 [95% CI 1.58 to 4.51]; P<0.001), vacuum/forceps assisted delivery (OR 1.88
      [95% CI 1.02 to 3.49]; P=0.04) and male sex (OR 1.55 [95% CI 1.00 to 2.38];
      P=0.05). CONCLUSION: Advice to vary infants' head positions needs to be
      communicated to parents/guardians well before the two-month well-child clinic
      visit. This could occur in the prenatal period by prenatal care providers or
      educators, or during the neonatal period by postpartum and public health nurses.
      Prevention education may be emphasized for parents/guardians of male infants and
      infants who have had assisted deliveries.

PMID- 25383000
TI  - Letter to the editor.

PMID- 25383001
TI  - Sexually transmitted infections in adolescents: Maximizing opportunities for
      optimal care.
AB  - Sexually transmitted infections are a growing public health concern in Canada,
      with rates of Chlamydia trachomatis infection, gonorrhea and syphilis increasing
      among adolescents and young adults. The present practice point outlines
      epidemiology, risk factors, laboratory testing and management for C trachomatis,
      Neisseria gonorrhoeae and Treponema pallidum, with a lesser focus on HIV. The
      need for test-of-cure and indications for further investigations are also
      discussed. The importance of maximizing opportunities to screen for and treat
      sexually transmitted infections in this age group is highlighted. 

PMID- 25383002
TI  - Vaccine recommendations for children and youth for the 2014/2015 influenza
      season.
AB  - The Canadian Paediatric Society continues to encourage annual influenza
      vaccination for ALL children and youth >=6 months of age. Recommendations from
      the National Advisory Committee on Immunization for the 2014/2015 influenza
      season include some important changes: Influenza vaccination is recommended for
      ALL individuals >=6 months of age, with particular focus on those at high risk of
      influenza-related complications and their close contacts. Definitions of high
      risk conditions and close contacts have not changed from those of 2013/2014.The
      preference for intranasal, live attenuated influenza vaccine (LAIV) over
      trivalent inactivated influenza vaccines for healthy children is restricted to
      individuals two to six years of age. There is insufficient evidence to recommend
      LAIV over trivalent inactivated influenza vaccines in older children or in
      children with chronic health conditions; either vaccine may be used unless there
      are specific contraindications.Quadrivalent influenza vaccines are expected to be
      available for the 2014/2015 season and may be used interchangeably with trivalent
      vaccines. They may offer improved protection.Trivalent or quadrivalent
      inactivated vaccines may be used in individuals with egg allergy; LAIV has not
      yet been evaluated in this population and is not recommended at this time. 

PMID- 25383003
TI  - Redefining feeding and eating disorders: What is avoidant/restrictive food intake
      disorder?

PMID- 25383004
TI  - Case 1: Unilateral leg swelling in a toddler.

PMID- 25383005
TI  - Case 2: Weight lost... and found.

PMID- 25383006
TI  - The development of lingual gestures in speech: experimental approach to language
      development.

PMID- 25383007
TI  - Three new species of Licania (Chrysobalanaceae) from Peru.
AB  - Recent collections received for identification contain three conspicuous new
      species for the mid altitude forests of Amazonian Peru. Licaniapalcazuensis,
      Licaniaapiknae and Licaniamonteagudensis are described as new and their
      relationship to other species is discussed. A key is provided for all the species
      of LicaniasubgenusLicaniasectionLicania known to occur in Peru. 

PMID- 25383008
TI  - Synopsis of Nekemias Raf., a segregate genus from Ampelopsis Michx. (Vitaceae)
      disjunct between eastern/southeastern Asia and eastern North America, with ten
      new combinations.
AB  - The genus Nekemias (Vitaceae) was first recognized by Rafinesque in 1838. It has
      been treated as a synonym of Ampelopsis Michx. Recent phylogenetic studies
      suggest that Ampelopsis as traditionally delimited is paraphyletic. To maintain
      the monophyly of each of the genera of Vitaceae, we herein segregate the
      Ampelopsissect.Leeaceifoliae lineage from Ampelopsis and recognize these taxa in
      Nekemias Raf., which has a disjunct distribution in eastern to southeastern Asia
      and eastern North America. Nomenclatural changes are made for nine species and
      one variety: Nekemiasarborea (L.) J. Wen & Boggan, Nekemiascantoniensis (Hook. &
      Arn.) J. Wen & Z.L. Nie, Nekemiascelebica (Suess.) J. Wen & Boggan,
      Nekemiaschaffanjonii (H. Lev. & Van.) J. Wen & Z.L. Nie, Nekemiasgongshanensis
      (C.L. Li) J. Wen & Z.L. Nie, Nekemiasgrossedentata (Hand.-Mazz.) J. Wen & Z.L.
      Nie, Nekemiashypoglauca (Hance) J. Wen & Z.L. Nie, Nekemiasmegalophylla (Diels &
      Gilg) J. Wen & Z.L. Nie, Nekemiasmegalophyllavar.jiangxiensis (W.T. Wang) J. Wen
      & Z.L. Nie, and Nekemiasrubifolia (Wall.) J. Wen & Z.L. Nie. A taxonomic key is
      provided for the genus to facilitate identification. 

PMID- 25383009
TI  - Dr. Roberto Miguel Klein Herbarium (FURB), Blumenau, Southern Brazil.
AB  - The premise of this study is to present the collection of the FURB herbarium, its
      collection area and type specimens, as well as its projects and contributions to
      the flora of the Subtropical Atlantic Forest. The FURB herbarium currently has
      nearly 41,000 records of vascular plants and has the largest collection of
      lycophytes and ferns in Southern Brazil, with more than 8,000 records. More than
      4,500 scanned images of 4,436 species are available online, and it is expected
      that the whole collection will be scanned in less than one year. There are 198
      families of angiosperms, 33 of ferns, three of lycophytes and six of gymnosperms.
      All collections of the Floristic and Forest Inventory of Santa Catarina project
      are recorded in FURB, which represents almost 35,000 herbarium specimens. The
      families with the largest number of species are: Cyperaceae (109 species),
      Rubiaceae (129), Solanaceae (131), Poaceae (155), Melastomataceae (157),
      Myrtaceae (257), Orchidaceae (288), Fabaceae (323), and Asteraceae (426), between
      angiosperms. Among the ferns and lycophytes are: Hymenophyllaceae (30),
      Thelypteridaceae (31), Aspleniaceae (32), Dryopteridaceae (43), Pteridaceae (54)
      and Polypodiaceae (60). There are five type specimens among them: one holotype,
      one isotype and three paratypes. To date, the FURB herbarium has donated 19,521
      herbarium duplicates for identification or expansion of other herbaria.

PMID- 25383010
TI  - Bidensmeyeri (Asteraceae, Coreopsideae): a new critically endangered species from
      Rapa, Austral Islands.
AB  - Bidensmeyeri (Asteraceae/Compositae) is described and illustrated from Rapa,
      Austral Islands, (French Polynesia). This new species is presumed to be most
      closely related to Bidenssaint-johniana from nearby Marotiri Island. Bidensmeyeri
      may be distinguished from Bidenssaint-johniana based on the length of the
      peduncle (3 cm versus 10 cm), apex of the inner involucral bracts (glabrous vs.
      puberulent), smaller leaves (2.0-2.3 cm vs. 5-6 cm), and the general smaller size
      of the new species. Known from less than 50 individuals and restricted to one
      remote location, Bidensmeyeri falls into the IUCN Critically Endangered (CR)
      category. The new species is named in honor of Dr. Jean-Yves Meyer, Delegation a
      la Recherche, Polynesie Francaise. 

PMID- 25383011
TI  - Dorstenialuamensis (Moraceae), a new species from eastern Democratic Republic of
      Congo.
AB  - A new species of Dorstenia L. (Moraceae), Dorstenialuamensis M.E.Leal, is
      described from the Luama Wildlife Reserve, west of Lake Tanganyika and north of
      the town of Kalemie in the eastern part of the Democratic Republic of Congo
      (DRC). This species is endemic to the region and differs from any of the other
      species by its fernlike lithophytic habit and lack of latex. A description and
      illustration of this species is presented here. Dorstenialuamensis M.E.Leal
      inhabits moist and shady vertical rock faces close to small waterfalls in the
      forest; the species is distributed in small populations within the type locality,
      and merits the conservation status of endangered (EN). 

PMID- 25383012
TI  - Four new species of Andean Pilea (Urticaceae), with additional notes on the genus
      in Venezuela.
AB  - Four new species of Pilea (Urticaceae) from the Andes of Venezuela are described
      and illustrated: Pileamatthewii sp. nov., Pileamiguelii sp. nov., Pileanicholasii
      sp. nov., and Pileanidiae sp. nov. The affinities of these species and their
      positions within the informal classifications of Pilea proposed by Weddell and
      Killip are discussed. Notes on other species of Pilea found in Venezuela also are
      presented. 

PMID- 25383013
TI  - Two new species of Tynanthus Miers (Bignonieae, Bignoniaceae) from Brazil.
AB  - Tynanthus is a genus of lianas that is broadly distributed through the
      Neotropics. Two new species of Tynanthus from Brazil are here described and
      illustrated: Tynanthusdensiflorus, from Amazonas, and Tynanthusespiritosantensis,
      from Espirito Santo. Tynanthusdensiflorus is recognized by the conspicuous
      interpetiolar glandular fields, a feature rarely found in Tynanthus, and the
      dense thyrses. Tynanthusespiritosantensis, on the other hand, is recognized by
      the bromeliad-like prophylls of the axillary buds and the lax thyrses.
      Information on the distribution, conservation status and morphologically similar
      species are provided. 

PMID- 25383014
TI  - Statistical extraction affects visually guided action.
AB  - The visual system summarizes average properties of ensembles of similar objects.
      We demonstrated an adaptation aftereffect of one such property, mean size,
      suggesting it is encoded along a single visual dimension (Corbett, et al., 2012),
      in a similar manner as basic stimulus properties like orientation and direction
      of motion. To further explore the fundamental nature of ensemble encoding, here
      we mapped the evolution of mean size adaptation over the course of visually
      guided grasping. Participants adapted to two sets of dots with different mean
      sizes. After adaptation, two test dots replaced the adapting sets. Participants
      first reached to one of these dots, and then judged whether it was larger or
      smaller than the opposite dot. Grip apertures were inversely dependent on the
      average dot size of the preceding adapting patch during the early phase of
      movements, and this aftereffect dissipated as reaches neared the target.
      Interestingly, perceptual judgments still showed a marked aftereffect, even
      though they were made after grasping was completed more-or-less veridically. This
      effect of mean size adaptation on early visually guided kinematics provides novel
      evidence that mean size is encoded fundamentally in both perception and action
      domains, and suggests that ensemble statistics not only influence our perceptions
      of individual objects but can also affect our physical interactions with the
      external environment.

PMID- 25383015
TI  - Evolution of households' responses to the groundwater arsenic crisis in
      Bangladesh: information on environmental health risks can have increasing
      behavioral impact over time.
AB  - A national campaign of well testing through 2003 enabled households in rural
      Bangladesh to switch, at least for drinking, from high-arsenic wells to
      neighboring lower-arsenic wells. We study the well-switching dynamics over time
      by re-interviewing, in 2008, a randomly selected subset of households in the
      Araihazar region who had been interviewed in 2005. Contrary to concerns that the
      impact of arsenic information on switching behavior would erode over time, we
      find that not only was 2003-2005 switching highly persistent but also new
      switching by 2008 doubled the share of households at unsafe wells who had
      switched. The passage of time also had a cost: 22% of households did not recall
      test results by 2008. The loss of arsenic knowledge led to staying at unsafe
      wells and switching from safe wells. Our results support ongoing well testing for
      arsenic to reinforce this beneficial information.

PMID- 25383016
TI  - The role of the amorphous phase on the biomimetic mineralization of collagen.
AB  - Bone is a hierarchically structured composite material whose basic building block
      is the mineralized collagen fibril, where the collagen is the scaffold into which
      the hydroxyapatite (HA) crystals nucleate and grow. Understanding the mechanisms
      of hydroxyapatite formation inside the collagen is key to unravelling
      osteogenesis. In this work, we employed a biomimetic in vitro mineralization
      system to investigate the role of the amorphous precursor calcium phosphate phase
      in the mineralization of collagen. We observed that the rate of collagen
      mineralization is highly dependent on the concentration of polyaspartic acid, an
      inhibitor of hydroxyapatite nucleation and inducer of intrafibrillar
      mineralization. The lower the concentration of the polymer, the faster the
      mineralization and crystallization. Addition of the non-collagenous protein C
      DMP1, a nucleator of hydroxyapatite, substantially accelerates mineral
      infiltration as well as HA nucleation. We have also demonstrated that Cu ions
      interfere with the mineralization process first by inhibiting the entry of the
      calcium phosphate into the collagen, and secondly by stabilizing the ACP, such
      that it does not convert into HA. Interestingly, under these conditions
      mineralization happens preferentially in the overlap regions of the collagen
      fibril. Our results show that the interactions between the amorphous precursor
      phase and the collagen fibril play an important role in the control over
      mineralization.

PMID- 25383017
TI  - Geocoding large population-level administrative datasets at highly resolved
      spatial scales.
AB  - Using geographic information systems to link administrative databases with
      demographic, social, and environmental data allows researchers to use spatial
      approaches to explore relationships between exposures and health. Traditionally,
      spatial analysis in public health has focused on the county, zip code, or tract
      level because of limitations to geocoding at highly resolved scales. Using 2005
      birth and death data from North Carolina, we examine our ability to geocode
      population-level datasets at three spatial resolutions - zip code, street, and
      parcel. We achieve high geocoding rates at all three resolutions, with statewide
      street geocoding rates of 88.0% for births and 93.2% for deaths. We observe
      differences in geocoding rates across demographics and health outcomes, with
      lower geocoding rates in disadvantaged populations and the most dramatic
      differences occurring across the urban-rural spectrum. Our results suggest highly
      resolved spatial data architectures for population-level datasets are viable
      through geocoding individual street addresses. We recommend routinely geocoding
      administrative datasets to the highest spatial resolution feasible, allowing
      public health researchers to choose the spatial resolution used in analysis based
      on an understanding of the spatial dimensions of the health outcomes and
      exposures being investigated. Such research, however, must acknowledge how
      disparate geocoding success across subpopulations may affect findings.

PMID- 25383018
TI  - Some new addition formulae for Weierstrass elliptic functions.
AB  - We present new addition formulae for the Weierstrass functions associated with a
      general elliptic curve. We prove the structure of the formulae in n-variables and
      give the explicit addition formulae for the 2- and 3-variable cases. These new
      results were inspired by new addition formulae found in the case of an
      equianharmonic curve, which we can now observe as a specialization of the results
      here. The new formulae, and the techniques used to find them, also follow the
      recent work for the generalization of Weierstrass functions to curves of higher
      genus.

PMID- 25383019
TI  - An instability theory for the formation of ribbed moraine, drumlins and mega
      scale glacial lineations.
AB  - We present a theory for the coupled flow of ice, subglacial water and subglacial
      sediment, which is designed to represent the processes which occur at the bed of
      an ice sheet. The ice is assumed to flow as a Newtonian viscous fluid, the water
      can flow between the till and the ice as a thin film, which may thicken to form
      streams or cavities, and the till is assumed to be transported, either through
      shearing by the ice, squeezing by pressure gradients in the till, or by fluvial
      sediment transport processes in streams or cavities. In previous studies, it was
      shown that the dependence of ice sliding velocity on effective pressure provided
      a mechanism for the generation of bedforms resembling ribbed moraine, while the
      dependence of fluvial sediment transport on water film depth provides a mechanism
      for the generation of bedforms resembling mega-scale glacial lineations. Here, we
      combine these two processes in a single model, and show that, depending largely
      on the granulometry of the till, instability can occur in a range of types which
      range from ribbed moraine through three-dimensional drumlins to mega-scale
      glacial lineations.

PMID- 25383020
TI  - Instability of quantum equilibrium in Bohm's dynamics.
AB  - We consider Bohm's second-order dynamics for arbitrary initial conditions in
      phase space. In principle, Bohm's dynamics allows for 'extended' non-equilibrium,
      with initial momenta not equal to the gradient of phase of the wave function (as
      well as initial positions whose distribution departs from the Born rule). We show
      that extended non-equilibrium does not relax in general and is in fact unstable.
      This is in sharp contrast with de Broglie's first-order dynamics, for which non
      standard momenta are not allowed and which shows an efficient relaxation to the
      Born rule for positions. On this basis, we argue that, while de Broglie's
      dynamics is a tenable physical theory, Bohm's dynamics is not. In a world
      governed by Bohm's dynamics, there would be no reason to expect to see an
      effective quantum theory today (even approximately), in contradiction with
      observation.

PMID- 25383021
TI  - Approximation of weak solution for the problem of a pH-gradient creation in
      isoelectrofocusing.
AB  - The mathematical model describing the stationary natural pH-gradient arising
      under the action of an electric field in an aqueous solution of ampholytes is
      constructed and investigated. The model is a part of a more general model of the
      isoelectrofocusing process. Investigation is based on the approximation of a weak
      solution by the piecewise continuous non-smooth functions. The method can be used
      for solving classes of problems for ordinary differential equations with a small
      parameter at the highest derivatives and the turning points.

PMID- 25383022
TI  - Macroscopic stress and strain in a doubly periodic array of dislocation dipoles.
AB  - It is known that in two-dimensional periodic arrays of dislocations the summation
      of the periodic image fields is conditionally convergent. This is due to the long
      range character of the elastic fields of dislocations. As a result, the stress
      field obtained for a doubly periodic array of dislocation dipoles may contain a
      spurious constant stress that depends on the adopted summation scheme. In the
      present work, we provide, based on micromechanical considerations, a simple
      physical explanation of the origin of the conditional convergence of lattice sums
      of image interactions. In this context, the spurious stresses are found in a
      closed form for an arbitrary elastic anisotropy, and this is achieved without
      using the stress field of an individual dislocation. An alternative procedure is
      also developed where the macroscopic spurious stresses are determined using the
      solution of the Eshelby's inclusion problem.

PMID- 25383023
TI  - Theoretical and experimental evidence of non-symmetric doubly localized rogue
      waves.
AB  - We present determinant expressions for vector rogue wave (RW) solutions of the
      Manakov system, a two-component coupled nonlinear Schrodinger (NLS) equation. As
      a special case, we generate a family of exact and non-symmetric RW solutions of
      the NLS equation up to third order, localized in both space and time. The derived
      non-symmetric doubly localized second-order solution is generated experimentally
      in a water wave flume for deep-water conditions. Experimental results, confirming
      the characteristic non-symmetric pattern of the solution, are in very good
      agreement with theory as well as with numerical simulations, based on the
      modified NLS equation, known to model accurately the dynamics of weakly nonlinear
      wave packets in deep water.

PMID- 25383024
TI  - Subglacial swamps.
AB  - The existence of both water and sediment at the bed of ice streams is well
      documented, but there is a lack of fundamental understanding about the mechanisms
      of ice, water and sediment interaction. We pose a model to describe subglacial
      water flow below ice sheets, in the presence of a deformable sediment layer.
      Water flows in a rough-bedded film; the ice is supported by larger clasts, but
      there is a millimetric water layer submerging the smaller particles. Partial
      differential equations describing the water film are derived from a description
      of the dynamics of ice, water and mobile sediment. We assume that sediment
      transport is possible, either as fluvial bedload, but more significantly by ice
      driven shearing and by internal squeezing. This provides an instability mechanism
      for rivulet formation; in the model, downstream sediment transport is compensated
      by lateral squeezing of till towards the incipient streams. We show that the
      model predicts the formation of shallow, swamp-like streams, with a typical depth
      of the order of centimetres. The swamps are stable features, typically with a
      width of the order of tens to hundreds of metres.

PMID- 25383025
TI  - The dynamics of mergers and acquisitions: ancestry as the seminal determinant.
AB  - Understanding the fundamental mechanisms behind the complex landscape of
      corporate mergers and acquisitions is of crucial importance to economies across
      the world. Adapting ideas from the fields of complexity and evolutionary dynamics
      to analyse business ecosystems, we show here that ancestry, i.e. the cumulative
      sum of historical mergers across all ancestors, is the key characteristic to
      company mergers and acquisitions. We verify this by comparing an agent-based
      model to an extensive range of business data, covering the period from the 1830s
      to the present day and a range of industries and geographies. This seemingly
      universal mechanism leads to imbalanced business ecosystems, with the emergence
      of a few very large, but sluggish 'too big to fail' entities, and very small,
      niche entities, thereby creating a paradigm where a configuration akin to
      effective oligopoly or monopoly is a likely outcome for free market systems.

PMID- 25383026
TI  - Magnetic phase transitions and magnetic entropy in the XY antiferromagnetic
      pyrochlores (Er1-x Y x )2Ti2O7.
AB  - We present the results of experimental determination of the heat capacity of the
      pyrochlore Er2Ti2O7 as a function of temperature (0.35-300 K) and magnetic field
      (up to 9 T), and for magnetically diluted solid solutions of the general formula
      (Er1-x Y x )2Ti2O7 (x<=0.471). On either doping or increase of magnetic field, or
      both, the Neel temperature first shifts to lower temperature until a critical
      point above which there is no well-defined transition but a Schottky-like anomaly
      associated with the splitting of the ground state Kramers doublet. By taking into
      account details of the lattice contribution to the heat capacity, we accurately
      isolate the magnetic contribution to the heat capacity and hence to the entropy.
      For pure Er2Ti2O7 and for (Er1-x Y x )2Ti2O7, the magnetic entropy as a function
      of temperature evolves with two plateaus: the first at [Formula: see text], and
      the other at [Formula: see text]. When a very high magnetic field is applied, the
      first plateau is washed out. The influence of dilution at low values is similar
      to the increase of magnetic field, as we show by examination of the critical
      temperature versus critical field curve in reduced terms.

PMID- 25383027
TI  - Levy flight movement patterns in marine predators may derive from turbulence
      cues.
AB  - The Levy-flight foraging hypothesis states that because Levy flights can optimize
      search efficiencies, natural selection should have led to adaptations for Levy
      flight foraging. Some of the strongest evidence for this hypothesis has come from
      telemetry data for sharks, bony fish, sea turtles and penguins. Here, I show that
      the programming for these Levy movement patterns does not need to be very
      sophisticated or clever on the predator's part, as these movement patterns would
      arise naturally if the predators change their direction of travel only after
      encountering patches of relatively strong turbulence (a seemingly natural
      response to buffeting). This is established with the aid of kinematic simulations
      of three-dimensional turbulence. Levy flights movement patterns are predicted to
      arise in all but the most quiescent of oceanic waters.

PMID- 25383028
TI  - Thermophysical and anion diffusion properties of (U x ,Th1-x )O2.
AB  - Using molecular dynamics, the thermophysical properties of the (U x ,Th1-x )O2
      system have been investigated between 300 and 3600 K. The thermal dependence of
      lattice parameter, linear thermal expansion coefficient, enthalpy and specific
      heat at constant pressure is explained in terms of defect formation and
      diffusivity on the oxygen sublattice. Vegard's law is approximately observed for
      solid solution thermal expansion below 2000 K. Different deviations from Vegard's
      law above this temperature occur owing to the different temperatures at which the
      solid solutions undergo the superionic transition (2500-3300 K). Similarly, a
      spike in the specific heat, associated with the superionic transition, occurs at
      lower temperatures in solid solutions that have a high U content.
      Correspondingly, oxygen diffusivity is higher in pure UO2 than in pure ThO2.
      Furthermore, at temperatures below the superionic transition, oxygen mobility is
      notably higher in solid solutions than in the end members. Enhanced diffusivity
      is promoted by lower oxygen-defect enthalpies in (U x ,Th1-x )O2 solid solutions.
      Unlike in UO2 and ThO2, there is considerable variety of oxygen vacancy and
      oxygen interstitial sites in solid solutions generating a wide range of property
      values. Trends in the defect enthalpies are discussed in terms of composition and
      the lattice parameter of (U x ,Th1-x )O2.

PMID- 25383029
TI  - Experimental study of transport of a dimer on a vertically oscillating plate.
AB  - It has recently been shown that a dimer, composed of two identical spheres
      rigidly connected by a rod, under harmonic vertical vibration can exhibit a self
      ordered transport behaviour. In this case, the mass centre of the dimer will
      perform a circular orbit in the horizontal plane, or a straight line if confined
      between parallel walls. In order to validate the numerical discoveries, we
      experimentally investigate the temporal evolution of the dimer's motion in both
      two- and three-dimensional situations. A stereoscopic vision method with a pair
      of high-speed cameras is adopted to perform omnidirectional measurements. All the
      cases studied in our experiments are also simulated using an existing numerical
      model. The combined investigations detail the dimer's dynamics and clearly show
      that its transport behaviours originate from a series of combinations of
      different contact states. This series is critical to our understanding of the
      transport properties in the dimer's motion and related self-ordered phenomena in
      granular systems.

PMID- 25383030
TI  - Energy-based analysis of biochemical cycles using bond graphs.
AB  - Thermodynamic aspects of chemical reactions have a long history in the physical
      chemistry literature. In particular, biochemical cycles require a source of
      energy to function. However, although fundamental, the role of chemical potential
      and Gibb's free energy in the analysis of biochemical systems is often overlooked
      leading to models which are physically impossible. The bond graph approach was
      developed for modelling engineering systems, where energy generation, storage and
      transmission are fundamental. The method focuses on how power flows between
      components and how energy is stored, transmitted or dissipated within components.
      Based on the early ideas of network thermodynamics, we have applied this approach
      to biochemical systems to generate models which automatically obey the laws of
      thermodynamics. We illustrate the method with examples of biochemical cycles. We
      have found that thermodynamically compliant models of simple biochemical cycles
      can easily be developed using this approach. In particular, both stoichiometric
      information and simulation models can be developed directly from the bond graph.
      Furthermore, model reduction and approximation while retaining structural and
      thermodynamic properties is facilitated. Because the bond graph approach is also
      modular and scaleable, we believe that it provides a secure foundation for
      building thermodynamically compliant models of large biochemical networks.

PMID- 25383031
TI  - Swelling-induced and controlled curving in layered gel beams.
AB  - We describe swelling-driven curving in originally straight and non-homogeneous
      beams. We present and verify a structural model of swollen beams, based on a new
      point of view adopted to describe swelling-induced deformation processes in
      bilayered gel beams, that is based on the split of the swelling-induced
      deformation of the beam at equilibrium into two components, both depending on the
      elastic properties of the gel. The method allows us to: (i) determine beam
      stretching and curving, once assigned the characteristics of the solvent bath and
      of the non-homogeneous beam, and (ii) estimate the characteristics of non
      homogeneous flat gel beams in such a way as to obtain, under free-swelling
      conditions, three-dimensional shapes. The study was pursued by means of
      analytical, semi-analytical and numerical tools; excellent agreement of the
      outcomes of the different techniques was found, thus confirming the strength of
      the method.

PMID- 25383033
TI  - Guaranteed resonance enclosures and exclosures for atoms and molecules.
AB  - In this paper, we confirm, with absolute certainty, a conjecture on a certain
      oscillatory behaviour of higher auto-ionizing resonances of atoms and molecules
      beyond a threshold. These results not only definitely settle a more than 30 year
      old controversy in Rittby et al. (1981 Phys. Rev. A24, 1636-1639
      (doi:10.1103/PhysRevA.24.1636)) and Korsch et al. (1982 Phys. Rev. A26, 1802-1803
      (doi:10.1103/PhysRevA.26.1802)), but also provide new and reliable information on
      the threshold. Our interval-arithmetic-based method allows one, for the first
      time, to enclose and to exclude resonances with guaranteed certainty. The
      efficiency of our approach is demonstrated by the fact that we are able to show
      that the approximations in Rittby et al. (1981 Phys. Rev. A24, 1636-1639
      (doi:10.1103/PhysRevA.24.1636)) do lie near true resonances, whereas the
      approximations of higher resonances in Korsch et al. (1982 Phys. Rev. A26, 1802
      1803 (doi:10.1103/PhysRevA.26.1802)) do not, and further that there exist two new
      pairs of resonances as suggested in Abramov et al. (2001 J. Phys. A34, 57-72
      (doi:10.1088/0305-4470/34/1/304)).

PMID- 25383034
TI  - Non-smooth Hopf-type bifurcations arising from impact-friction contact events in
      rotating machinery.
AB  - We analyse the novel dynamics arising in a nonlinear rotor dynamic system by
      investigating the discontinuity-induced bifurcations corresponding to collisions
      with the rotor housing (touchdown bearing surface interactions). The simplified
      Foppl/Jeffcott rotor with clearance and mass unbalance is modelled by a two
      degree of freedom impact-friction oscillator, as appropriate for a rigid rotor
      levitated by magnetic bearings. Two types of motion observed in experiments are
      of interest in this paper: no contact and repeated instantaneous contact. We
      study how these are affected by damping and stiffness present in the system using
      analytical and numerical piecewise-smooth dynamical systems methods. By studying
      the impact map, we show that these types of motion arise at a novel non-smooth
      Hopf-type bifurcation from a boundary equilibrium bifurcation point for certain
      parameter values. A local analysis of this bifurcation point allows us a complete
      understanding of this behaviour in a general setting. The analysis identifies
      criteria for the existence of such smooth and non-smooth bifurcations, which is
      an essential step towards achieving reliable and robust controllers that can take
      compensating action.

PMID- 25383035
TI  - An introduction to the mechanics of the lasso.
AB  - Trick roping evolved from humble origins as a cattle-catching tool into a sport
      that delights audiences all over the world with its complex patterns or 'tricks'.
      Its fundamental tool is the lasso, formed by passing one end of a rope through a
      small loop (the honda) at the other end. Here, we study the mechanics of the
      simplest rope trick, the Flat Loop, in which the rope is driven by the steady
      circular motion of the roper's hand in a horizontal plane. We first consider the
      case of a fixed (non-sliding) honda. Noting that the rope's shape is steady in
      the reference frame rotating with the hand, we analyse a string model in which
      line tension is balanced by the centrifugal force and the rope's weight. We use
      numerical continuation to classify the steadily rotating solutions in a
      bifurcation diagram and analyse their stability. In addition to Flat Loops, we
      find planar 'coat-hanger' solutions, and whirling modes in which the loop
      collapses onto itself. Next, we treat the more general case of a honda that can
      slide due to a finite coefficient of friction of the rope on itself. Using
      matched asymptotic expansions, we resolve the shape of the rope in the boundary
      layer near the honda where the rope's bending stiffness cannot be neglected. We
      use this solution to derive a macroscopic criterion for the sliding of the honda
      in terms of the microscopic Coulomb static friction criterion. Our predictions
      agree well with rapid-camera observations of a professional trick roper and with
      laboratory experiments using a 'robo-cowboy'.

PMID- 25383032
TI  - Three-dimensionally deformable, highly stretchable, permeable, durable and
      washable fabric circuit boards.
AB  - This paper reports fabric circuit boards (FCBs), a new type of circuit boards,
      that are three-dimensionally deformable, highly stretchable, durable and washable
      ideally for wearable electronic applications. Fabricated by using computerized
      knitting technologies at ambient dry conditions, the resultant knitted FCBs
      exhibit outstanding electrical stability with less than 1% relative resistance
      change up to 300% strain in unidirectional tensile test or 150% membrane strain
      in three-dimensional ball punch test, extraordinary fatigue life of more than 1
      000 000 loading cycles at 20% maximum strain, and satisfactory washing capability
      up to 30 times. To the best of our knowledge, the performance of new FCBs has far
      exceeded those of previously reported metal-coated elastomeric films or other
      organic materials in terms of changes in electrical resistance, stretchability,
      fatigue life and washing capability as well as permeability. Theoretical analysis
      and numerical simulation illustrate that the structural conversion of knitted
      fabrics is attributed to the effective mitigation of strain in the conductive
      metal fibres, hence the outstanding mechanical and electrical properties. Those
      distinctive features make the FCBs particularly suitable for next-to-skin
      electronic devices. This paper has further demonstrated the application potential
      of the knitted FCBs in smart protective apparel for in situ measurement during
      ballistic impact.

PMID- 25383036
TI  - A constraint-free phase field model for ferromagnetic domain evolution.
AB  - A continuum constraint-free phase field model is proposed to simulate the
      magnetic domain evolution in ferromagnetic materials. The model takes the polar
      and azimuthal angles (theta1,theta2), instead of the magnetization unit vector
      m(m1,m2,m3), as the order parameters. In this way, the constraint on the
      magnetization magnitude can be exactly satisfied automatically, and no special
      numerical treatment on the phase field evolution is needed. The phase field model
      is developed from a thermodynamic framework which involves a configurational
      force system for theta1 and theta2. A combination of the configurational force
      balance and the second law of thermodynamics leads to thermodynamically
      consistent constitutive relations and a generalized evolution equation for the
      order parameters (theta1,theta2). Beneficial from the constraint-free model, the
      three-dimensional finite-element implementation is straightforward, and the
      degrees of freedom are reduced by one. The model is shown to be capable of
      reproducing the damping-dependent switching dynamics, and the formation and
      evolution of domains and vortices in ferromagnetic materials under the external
      magnetic or mechanical loading. Particularly, the calculated out-of-plane
      component of magnetization in a vortex is verified by the corresponding
      experimental results, as well as the motion of the vortex under a magnetic field.

PMID- 25383038
TI  - Torsional locomotion.
AB  - One edge of an elastic rod is inserted into a friction-less and fitting socket
      head, whereas the other edge is subjected to a torque, generating a uniform
      twisting moment. It is theoretically shown and experimentally proved that,
      although perfectly smooth, the constraint realizes an expulsive axial force on
      the elastic rod, which amount is independent of the shape of the socket head. The
      axial force explains why screwdrivers at high torque have the tendency to
      disengage from screw heads and demonstrates torsional locomotion along a
      perfectly smooth channel. This new type of locomotion finds direct evidence in
      the realization of a 'torsional gun', capable of transforming torque into
      propulsive force.

PMID- 25383037
TI  - Continuum mechanics beyond the second law of thermodynamics.
AB  - The results established in contemporary statistical physics indicating that, on
      very small space and time scales, the entropy production rate may be negative,
      motivate a generalization of continuum mechanics. On account of the fluctuation
      theorem, it is recognized that the evolution of entropy at a material point is
      stochastically (not deterministically) conditioned by the past history, with an
      increasing trend of average entropy production. Hence, the axiom of Clausius
      Duhem inequality is replaced by a submartingale model, which, by the Doob
      decomposition theorem, allows classification of thermomechanical processes into
      four types depending on whether they are conservative or not and/or conventional
      continuum mechanical or not. Stochastic generalizations of thermomechanics are
      given in the vein of either thermodynamic orthogonality or primitive
      thermodynamics, with explicit models formulated for Newtonian fluids with,
      respectively, parabolic or hyperbolic heat conduction. Several random field
      models of the martingale component, possibly including spatial fractal and Hurst
      effects, are proposed. The violations of the second law are relevant in those
      situations in continuum mechanics where very small spatial and temporal scales
      are involved. As an example, we study an acceleration wavefront of nanoscale
      thickness which randomly encounters regions in the medium characterized by a
      negative viscosity coefficient.

PMID- 25383039
TI  - Extending the molecular clutch beyond actin-based cell motility.
AB  - Many cell movements occur via polymerization of the actin cytoskeleton beneath
      the plasma membrane at the front of the cell, forming a protrusion called a
      lamellipodium, while myosin contraction squeezes forward the back of the cell. In
      what is known as the "molecular clutch" description of cell motility, forward
      movement results from the engagement of the acto-myosin motor with cell-matrix
      adhesions, thus transmitting force to the substrate and producing movement.
      However during cell translocation, clutch engagement is not perfect, and as a
      result, the cytoskeleton slips with respect to the substrate, undergoing backward
      (retrograde) flow in the direction of the cell body. Retrograde flow is therefore
      inversely proportional to cell speed and depends on adhesion and acto-myosin
      dynamics. Here we asked whether the molecular clutch was a general mechanism by
      measuring motility and retrograde flow for the Caenorhabditis elegans sperm cell
      in different adhesive conditions. These cells move by adhering to the substrate
      and emitting a dynamic lamellipodium, but the sperm cell does not contain an acto
      myosin cytoskeleton. Instead the lamellipodium is formed by the assembly of Major
      Sperm Protein (MSP), which has no biochemical or structural similarity to actin.
      We find that these cells display the same molecular clutch characteristics as
      acto-myosin containing cells. We further show that retrograde flow is produced
      both by cytoskeletal assembly and contractility in these cells. Overall this
      study shows that the molecular clutch hypothesis of how polymerization is
      transduced into motility via adhesions is a general description of cell movement
      regardless of the composition of the cytoskeleton.

PMID- 25383040
TI  - Exploring nicotinamide cofactor promiscuity in NAD(P)H-dependent flavin
      containing monooxygenases (FMOs) using natural variation within the phosphate
      binding loop. Structure and activity of FMOs from Cellvibrio sp. BR and
      Pseudomonas stutzeri NF13.
AB  - Flavin-containing monooxygenases (FMOs) catalyse asymmetric oxidation reactions
      that have potential for preparative organic synthesis, but most use the more
      expensive, phosphorylated nicotinamide cofactor NADPH to reduce FAD to FADH2
      prior to formation of the (hydro)peroxy intermediate required for substrate
      oxygenation. A comparison of the structures of NADPH-dependent FMO from
      Methylophaga aminisulfidivorans (mFMO) and SMFMO from Stenotrophomonas
      maltophilia, which is able to use both NADPH and NADH, suggested that the
      promiscuity of the latter enzyme may be due in part to the substitution of an Arg
      Thr couple in the NADPH phosphate recognition site in mFMO, for a Gln-His couple
      in SMFMO (Jensen et al., 2012, Chembiochem, 13, 872-878). Natural variation
      within the phosphate binding region, and its influence on nicotinamide cofactor
      promiscuity, was explored through the cloning, expression, characterisation and
      structural studies of FMOs from Cellvibrio sp. BR (CFMO) and Pseudomonas stutzeri
      NF13 (PSFMO), which possess Thr-Ser and Gln-Glu in the putative phosphate
      recognition positions, respectively. CFMO and PSFMO displayed 5- and 1.5-fold
      greater activity, respectively, than SMFMO for the reduction of FAD with NADH,
      and were also cofactor promiscuous, displaying a ratio of activity with
      NADH:NADPH of 1.7:1 and 1:1.3, respectively. The structures of CFMO and PSFMO
      revealed the context of the phosphate binding loop in each case, and also
      clarified the structure of the mobile helix-loop-helix motif that appears to
      shield the FAD-binding pocket from bulk solvent in this class of FMOs, a feature
      that was absent from the structure of SMFMO.

PMID- 25383041
TI  - Mn oxidation states in tri- and tetra-nuclear Mn compounds structurally relevant
      to photosystem II: Mn K-edge X-ray absorption and Kbeta X-ray emission
      spectroscopy studies.
AB  - X-Ray spectroscopy is used to examine the effect of the manganese oxidation state
      for a series of Mn model compounds. Sensitive to Mn oxidation and structural
      symmetry, X-ray absorption and emission spectroscopy (XAS and XES) provide
      complementary insights. However, few benchmark examples of complexes with similar
      structures but in different oxidation states are available to evaluate data from
      unknown structures like the oxygen evolving complex (OEC) of Photosystem II
      (PSII). This study examines two types of compounds prepared in a variety of Mn
      oxidation states and which possess chemical structures with Mn-Mn interactions
      (~2.7 A and ~3.3 A) that have been observed in the OEC. Model complexes with core
      compositions Mn3O and Mn4O2 contain combinations of Mn in either a reduced (II)
      or oxidized (III) state. Within each set of compounds, complexes with higher Mn
      oxidation states have absorption K-edge energy values that are higher (1.6-2.2
      eV) than those of their more reduced counterparts. This trend is accordingly
      reversed in the Kbeta emission spectroscopy where the first moment energy values
      are lower (0.09-0.12 eV) for compounds with higher Mn oxidation states. We will
      discuss in detail, how these trends can be quantitatively used to characterize
      the effects of the Mn oxidation state as well as the surrounding ligand
      environment on the observed X-ray spectra. The results are discussed with respect
      to previously obtained data on different S-states of the OEC.

PMID- 25383042
TI  - Understanding human management of automation errors.
AB  - Automation has the potential to aid humans with a diverse set of tasks and
      support overall system performance. Automated systems are not always reliable,
      and when automation errs, humans must engage in error management, which is the
      process of detecting, understanding, and correcting errors. However, this process
      of error management in the context of human-automation interaction is not well
      understood. Therefore, we conducted a systematic review of the variables that
      contribute to error management. We examined relevant research in human-automation
      interaction and human error to identify critical automation, person, task, and
      emergent variables. We propose a framework for management of automation errors to
      incorporate and build upon previous models. Further, our analysis highlights
      variables that may be addressed through design and training to positively
      influence error management. Additional efforts to understand the error management
      process will contribute to automation designed and implemented to support safe
      and effective system performance.

PMID- 25383043
TI  - A method for preparation and cleaning of uniformly sized arsenopyrite particles.
AB  - BACKGROUND: The oxidative dissolution of sulfide minerals, such as arsenopyrite
      (FeAsS), is of critical importance in many geochemical systems. A comprehensive
      understanding of their dissolution rates entails careful preparation of the
      mineral surface. Measurements of dissolution rates of arsenic from arsenopyrite
      are dependent on the size and degree of oxidation of its particles, among other
      factors. In this work, a method was developed for preparation and cleaning of
      arsenopyrite particles with size range of 150-250 MUm. Four different cleaning
      methods were evaluated for effectiveness based on the removal of oxidized species
      of iron (Fe), arsenic (As) and sulfur (S) from the surface. The percentage
      oxidation of the surface was determined using X-ray photoelectron spectroscopy
      (XPS), and surface stoichiometry was measured using scanning electron microscopy 
      energy dispersive X-ray spectroscopy (SEM-EDS). RESULTS: Results indicate that
      sonicating the arsenopyrite particles and then cleaning them with 12N HCl
      followed by 50% ethanol, and drying in nitrogen was the most effective method.
      This method was successful in greatly reducing the oxide species of Fe while
      completely removing oxides of As and S from the arsenopyrite surface.
      CONCLUSIONS: Although sonication and acid cleaning have been widely used for
      mineral preparation, the method described in this study can significantly reduce
      grain size heterogeneity as well as surface oxidation, which enables greater
      control in surface and dissolution experiments.

PMID- 25383044
TI  - Ursolic acid induces cell cycle arrest and apoptosis of gallbladder carcinoma
      cells.
AB  - BACKGROUND: Ursolic acid (UA), a plant extract used in traditional Chinese
      medicine, exhibits potential anticancer effects in various human cancer cell
      lines in vitro. In the present study, we evaluated the anti-tumoral properties of
      UA against gallbladder carcinoma and investigated the potential mechanisms
      responsible for its effects on proliferation, cell cycle arrest and apoptosis in
      vitro. METHODS: The anti-tumor activity of UA against GBC-SD and SGC-996 cells
      was assessed using MTT and colony formation assays. An annexin V/PI double
      staining assay was used to detect cell apoptosis. Cell cycle changes were
      detected using flow cytometry. Rhodamine 123 staining was used to assess the
      mitochondrial membrane potential (DeltaPsim) and validate UA's ability to induce
      apoptosis in both cell lines. The effectiveness of UA in gallbladder cancer was
      further verified in vivo by establishing a xenograft GBC model in nude mice.
      Finally, the expression levels of cell cycle- and apoptosis-related proteins were
      analyzed by western blotting. RESULTS: Our results suggest that UA can
      significantly inhibit the growth of gallbladder cancer cells. MTT and colony
      formation assays indicated dose-dependent decreases in cell proliferation. S
      phase arrest was observed in both cell lines after treatment with UA. Annexin
      V/PI staining suggested that UA induced both early and late phases of apoptosis.
      UA also decreased DeltaPsim and altered the expression of molecules regulating
      the cell cycle and apoptosis. In vivo study showed intraperitoneally injection of
      UA can significantly inhibited the growth of xenograft tumor in nude mice and the
      inhibition efficiency is dose related. Activation of caspase-3,-9 and PARP
      indicated that mitochondrial pathways may be involved in UA-induced apoptosis.
      CONCLUSIONS: Taken together, these results suggest that UA exhibits significant
      anti-tumor effects by suppressing cell proliferation, promoting apoptosis and
      inducing 7cell cycle arrest both in vitro and in vivo. It may be a potential
      agent for treating gallbladder cancer.

PMID- 25383045
TI  - Antioxidant and anti-inflammatory effects of selenium in oral buccal mucosa and
      small intestinal mucosa during intestinal ischemia-reperfusion injury.
AB  - BACKGROUND: The aim of this study were to investigate whether selenium treatment
      attenuates lipid peroxidation and downregulates the NF-kappaB pathway in small
      intestinal mucosa and to examine whether the effect of selenium is also observed
      in oral buccal mucosa, during small intestinal IR injury. MATERIALS AND METHODS:
      Eighteen rats were assigned into three groups: sham, IR, and IR + selenium.
      Saline or selenium was administered through a tail vein. 24 hours later, the
      superior mesenteric artery was exposed and clamped in the IR and IR + selenium
      groups. After ischemic and reperfusion period, animals were sacrificed and oral
      buccal mucosa and small intestinal mucosa were harvested. RESULTS: Glutathione
      peroxidase activity and cytoplasmic IkappaB-alpha expression was higher in the IR
      + selenium group than that in the IR group. A malondialdehyde level, cytoplasmic
      phosphorylated inhibitor kappaB-alpha, nuclear NF-kappaB p65 expressions, and NF
      kappaB p65 DNA-binding activity were lower in the IR + selenium group than those
      in the IR group. CONCLUSION: A selenium treatment may cause increased GPx
      activity, attenuated lipid peroxidation, and downregulated the NF-kappaB pathway
      during small intestinal IR injury. Furthermore, these therapeutic benefits of
      selenium can be observed in oral buccal mucosa as well as small intestinal
      mucosa.

PMID- 25383046
TI  - Examining explanatory biases in young children's biological reasoning.
AB  - Despite the well-established literature on explanation in early childhood, little
      is known about what constrains children's explanations. State change and negative
      outcomes were examined as potential explanatory biases in the domain of naive
      biology, extending upon previous work in the domain of naive physics. In two
      studies, preschool children (N = 70, 3- to 5-year-olds) were informed of the
      distinct health outcomes of characters in four between-subjects conditions (i.e.,
      becoming ill, recovering from illness, continuous health, and continuous illness)
      and asked to provide explanations. Whereas children in both studies provided
      relevant information for health outcomes, they more often explained outcomes that
      included a salient health state change. Presence of a state change also
      influenced the interpretation of potentially relevant information and improved
      memory for health outcomes. We discuss how biases in children's explanations
      constrain children's reasoning and may exacerbate difficulties with reasoning
      about important health-related topics such as illness prevention.

PMID- 25383047
TI  - Body Image Distortions, Weight, and Depression in Adolescent Boys: Longitudinal
      Trajectories into Adulthood.
AB  - Depressive symptoms are common among the U.S. population, yet research into
      prospective risk factors of depression among men is limited. Distorted body image
      is also prevalent among adolescent boys, and may be linked with elevated
      depression; however, longitudinal associations have rarely been measured. Thus,
      the aim of the current study was to assess the prospective relationship between
      forms of body image distortion and depressive symptoms among adolescent boys,
      into adulthood. Data were extracted from the National Longitudinal Study of
      Adolescent Health. Participants were 2,139 U.S. adolescent boys (M age = 16) who
      were followed prospectively over 13-years (1996 to 2009), into adulthood.
      Longitudinal mixed-level modeling was employed to assess the temporal prediction
      of body image distortion on symptoms of depression. Results revealed that boys
      who were average weight and viewed themselves as either very underweight (very
      underweight distorted; Cohen's d = .47) or overweight (overweight distorted;
      Cohen's d = .29) reported significantly higher levels of depressive symptoms
      compared to boys who accurately viewed their weight as average; this effect
      remained constant over the 13-year study period. These findings indicated that
      distortions in body image, particularly extreme distortions, are risk factors for
      elevated depressive symptoms among adolescent boys, and persist into early
      adulthood.

PMID- 25383048
TI  - Spectrum Identification using a Dynamic Bayesian Network Model of Tandem Mass
      Spectra.
AB  - Shotgun proteomics is a high-throughput technology used to identify unknown
      proteins in a complex mixture. At the heart of this process is a prediction task,
      the spectrum identification problem, in which each fragmentation spectrum
      produced by a shotgun proteomics experiment must be mapped to the peptide
      (protein subsequence) which generated the spectrum. We propose a new algorithm
      for spectrum identification, based on dynamic Bayesian networks, which
      significantly out-performs the de-facto standard tools for this task: SEQUEST and
      Mascot.

PMID- 25383049
TI  - Use of Cross-Linked Poly(ethylene glycol)-Based Hydrogels for Protein
      Crystallization.
AB  - Poly(ethylene glycol) (PEG) hydrogels are highly biocompatible materials
      extensively used for biomedical and pharmaceutical applications, controlled drug
      release, and tissue engineering. In this work, PEG cross-linked hydrogels,
      synthesized under various conditions, were used to grow lysozyme crystals by the
      counterdiffusion technique. Crystallization experiments were conducted using a
      three-layer arrangement. Results demonstrated that PEG fibers were incorporated
      within lysozyme crystals controlling the final crystal shape. PEG hydrogels also
      induced the nucleation of lysozyme crystals to a higher extent than agarose. PEG
      hydrogels can also be used at higher concentrations (20-50% w/w) as a separation
      chamber (plug) in counterdiffusion experiments. In this case, PEG hydrogels
      control the diffusion of the crystallization agent and therefore may be used to
      tailor the supersaturation to fine-tune crystal size. As an example, insulin
      crystals were grown in 10% (w/w) PEG hydrogel. The resulting crystals were of an
      approximate size of 500 MUm.

PMID- 25383051
TI  - Craniomaxillofacial distraction osteogenesis.

PMID- 25383050
TI  - Raymond J. Harshbarger III, MD, FACS, FAAP.

PMID- 25383052
TI  - Posterior cranial vault distraction osteogenesis: evolution of technique.
AB  - The rapid growth of the brain in the first few years of life drives the expansion
      of the cranial vault. This expansion occurs primarily at the cranial sutures;
      premature fusion of these results in growth restriction perpendicular to the axis
      of the suture. The result of this is physical deformation of the cranial and
      facial skeleton, as well as the distortion of the underling brain and its
      physiology. These patients can present with symptoms of raised intracranial
      pressure, neurodevelopmental delay, as well as the morphological features of
      craniosynostosis. Acquired conditions such as the slit ventricle syndrome may
      also result in cephalocranial disproportion with these clinical features.
      Traditional vault remodeling surgery is able to correct the physical
      abnormalities as well as correcting cephalocranial disproportion. Its limitations
      include the degree of scalp expansion achievable as well as resulting defects in
      the bone. The use of distraction osteogenesis of the cranial vault permits a
      controlled expansion in a predetermined vector in a gradual manner. When used in
      the calvarium, this combines the benefits of tissue expansion on the scalp, as
      well as stimulating the production of new bone, reducing the defects resulting
      from expansion. In this review, the authors describe some of the surgical
      considerations important to the use of this technique. This includes the relevant
      anatomy and technical aspects illustrated with the use of clinical cases.
      Finally, they present a summary of their experience and discuss the complications
      associated with cranial vault distraction osteogenesis. 

PMID- 25383053
TI  - An Update on Midface Advancement Using Le Fort II and III Distraction
      Osteogenesis.
AB  - Le Fort II and III distraction osteogenesis (DO) is a powerful tool in the
      craniofacial armamentarium that is most often employed to treat patients with
      craniofacial syndromes such as Crouzon, Apert, or Pfeiffer syndrome who present
      with midfacial retrusion, shallow orbits, exorbitism, malocclusion, obstructive
      sleep apnea and facial imbalance. In this article, the authors will provide the
      reader with an update on techniques for the treatment of various forms of
      midfacial retrusion. 

PMID- 25383054
TI  - Le fort I maxillary advancement using distraction osteogenesis.
AB  - Treatment of maxillary hypoplasia has traditionally involved conventional Le Fort
      I osteotomies and advancement. Advancements of greater than 10 mm risk
      significant relapse. This risk is greater in the cleft lip and palate population,
      whose anatomy and soft tissue scarring from prior procedures contributes to
      instability of conventional maxillary advancement. Le Fort I advancement with
      distraction osteogenesis has emerged as viable, stable treatment modality
      correction of severe maxillary hypoplasia in cleft, syndromic, and noncleft
      patients. In this article, the authors provide a review of current data and
      recommendations concerning Le Fort I advancement with distraction osteogenesis.
      In addition, they outline their technique for treating severe maxillary
      hypoplasia with distraction osteogenesis using internal devices. 

PMID- 25383055
TI  - Neonatal mandibular distraction osteogenesis.
AB  - Mandibular distraction has revolutionized the treatment of Robin sequence
      associated with severe airway obstruction. The distraction technique remains the
      only intervention that directly corrects mandibular hypoplasia and the
      retropositioned tongue, providing efficient relief of airway stenosis. Multiple
      studies have demonstrated the efficacy of distraction in avoiding tracheostomy
      and decreasing the severity airway obstruction in this patient population. The
      benefit to avoiding tracheostomy and relieving airway obstruction is superior to
      that of tongue-lip adhesion. It is, therefore, not surprising that mandibular
      distraction has become the first-line intervention at many centers for the
      surgical treatment of Robin sequence. The complication profile associated with
      mandibular distraction appears low; the most common complication is infection,
      which can be treated by antibiotics alone. The severity of airway obstruction can
      be quantified by polysomnogram: This tool has become one of the most widely used
      objective metrics in the Robin sequence population. Therefore indications for
      surgery, timing of palatoplasty and long-term assessment of airway function
      should be performed in conjunction with sleep study analysis. The effects of
      mandibular lengthening on feeding difficulty in Robin sequence patient remains a
      topic of controversy. Studies have demonstrated conflicting results: This can be
      an area of future study. Agreed-upon indications for surgery and definitive
      protocols of care have yet to be formulized; future research should focus on
      achieving these goals. Such studies would require agreed-upon terminology for
      Robin sequence, an increase in comparative and prospective analysis, and the use
      of quantifiable metrics of clinical results. 

PMID- 25383056
TI  - Orthodontic considerations for maxillary distraction osteogenesis in growing
      patients with cleft lip and palate using internal distractors.
AB  - The orthodontist plays a key role in the selection of the optimal treatment for
      patients followed by a craniofacial team. For patients with cleft lip and palate,
      the need for multidisciplinary treatment planning and sequentially staged
      treatment is essential for successful patient outcomes. The technique of Le Fort
      I distraction osteogenesis of the maxilla using an internal device is potentially
      a predictable, stable, and convenient option for the correction of severe
      maxillary hypoplasia. It is an alternative option for treatment of maxillary
      hypoplasia in growing patients. In this article, the authors describe the
      orthodontist's approach to the management of cleft patients with severe maxillary
      deficiency with the use of an internal distraction device. The information is
      presented with a focus on the clinical aspects of treatment, using case
      illustrations and appropriate literature. 

PMID- 25383057
TI  - Presence of an HIV Testing Program Lowers the Prevalence of Unprotected Insertive
      Anal Intercourse inside a Gay Bathhouse among HIV-negative and HIV-unknown
      Patrons.
AB  - This study sought to determine whether the presence of HIV testing inside a gay
      bathhouse reduced sexual risk behavior among patrons. A two-stage, time
      probability, cluster sample design recruited men exiting a northern California
      bathhouse in the last 5 weeks of 2001 (N=440), when no HIV testing was offered
      inside the bathhouse, and again in the last 5 weeks of 2002 (N=412) when HIV
      testing was offered 5 days a week. Separate logistic regression analyses compared
      a 2002 HIV testing exposure subgroup to both a 2001 non-exposure subgroup and a
      2002 non-exposure subgroup for differences in sexual risk behavior during the
      bathhouse visit. Prevalence of unprotected insertive anal intercourse was
      significantly lower in the 2002 exposure subgroup than in the 2002 non-exposure
      subgroup. Similar results obtained when HIV-positive respondents were excluded.
      These results indicate on-site HIV testing has a preventive effect on some sexual
      risk behavior inside the bathhouse.

PMID- 25383058
TI  - Characterization and Remediation of Chlorinated Volatile Organic Contaminants in
      the Vadose Zone: An Overview of Issues and Approaches.
AB  - Contamination of vadose-zone systems by chlorinated solvents is widespread, and
      poses significant potential risk to human health through impacts on groundwater
      quality and vapor intrusion. Soil vapor extraction (SVE) is the presumptive
      remedy for such contamination, and has been used successfully for innumerable
      sites. However, SVE operations typically exhibit reduced mass-removal
      effectiveness at some point due to the impact of poorly accessible contaminant
      mass and associated mass-transfer limitations. Assessment of SVE performance and
      closure is currently based on characterizing contaminant mass discharge
      associated with the vadose-zone source, and its impact on groundwater or vapor
      intrusion. These issues are addressed in this overview, with a focus on
      summarizing recent advances in our understanding of the transport,
      characterization, and remediation of chlorinated solvents in the vadose zone. The
      evolution of contaminant distribution over time and the associated impacts on
      remediation efficiency will be discussed, as will the potential impact of
      persistent sources on groundwater quality and vapor intrusion. In addition,
      alternative methods for site characterization and remediation will be addressed.

PMID- 25383059
TI  - Traditional Chinese Medicine for Fibromyalgia.

PMID- 25383062
TI  - Electronic Polarizability and the Effective Pair Potentials of Water.
AB  - Employing the continuum dielectric model for electronic polarizability, we have
      developed a new consistent procedure for parameterization of the effective
      nonpolarizable potential of liquid water. The model explains the striking
      difference between the value of water dipole moment MU~3D reported in recent ab
      initio and experimental studies with the value MUeff ~2.3D typically used in the
      empirical potentials, such as TIP3P or SPC/E. It is shown that the consistency of
      the parameterization scheme can be achieved if the magnitude of the effective
      dipole of water is understood as a scaled value [Formula: see text], where
      epsilonel =1.78 is the electronic (high-frequency) dielectric constant of water,
      and a new electronic polarization energy term, missing in the previous theories,
      is included. The new term is evaluated by using Kirkwood - Onsager theory. The
      new scheme is fully consistent with experimental data on enthalpy of
      vaporization, density, diffusion coefficient, and static dielectric constant. The
      new theoretical framework provides important insights into the nature of the
      effective parameters, which is crucial when the computational models of liquid
      water are used for simulations in different environments, such as proteins, or
      for interaction with solutes.

PMID- 25383061
TI  - Effects of Parental Interaction on Infant Vocalization Rate, Variability and
      Vocal Type.
AB  - Examination of infant vocalization patterns across interactive and noninteractive
      contexts may facilitate better understanding of early communication development.
      In the current study, with 24 infant-parent dyads, infant volubility increased
      significantly when parent interaction ceased (presenting a "still face," or SF)
      after a period of normal interaction ("face-to-face," or FF). Infant volubility
      continued at the higher rate than in FF when the parent re-engaged ("reunion," or
      RE). Additionally, during SF, the variability in volubility across infants
      decreased, suggesting the infants adopted relatively similar rates of
      vocalization to re-engage the parent. The pattern of increasing volubility in SF
      was seen across all of the most common speech-like vocal types of the first half
      year of life (e.g., full vowels, quasivowels, squeals, growls). Parent and infant
      volubility levels were not significantly correlated. The findings suggest that by
      six months of age infants have learned that their vocalizations have social value
      and that changes in volubility can affect parental engagement.

PMID- 25383063
TI  - When a situation is "not black or white": Using adaptive leadership to address
      complex challenges in nursing home care.

PMID- 25383060
TI  - Population Genomics of Human Adaptation.
AB  - Recent advances in genotyping technologies have facilitated genome-wide scans for
      natural selection. Identification of targets of natural selection will shed light
      on processes of human adaptation and evolution and could be important for
      identifying variation that influences both normal human phenotypic variation as
      well as disease susceptibility. Here we focus on studies of natural selection in
      modern humans who originated ~200,000 years go in Africa and migrated across the
      globe ~50,000 - 100,000 years ago. Movement into new environments, as well as
      changes in culture and technology including plant and animal domestication,
      resulted in local adaptation to diverse environments. We summarize statistical
      approaches for detecting targets of natural selection and for distinguishing the
      effects of demographic history from natural selection. On a genome-wide scale,
      immune-related genes appear to be major targets of positive selection. Genes
      associated with reproduction and fertility also appear to be fast evolving.
      Additional examples of recent human adaptation include genes associated with
      lactase persistence, eccrine glands, and response to hypoxia. Lastly, we
      emphasize the need to supplement scans of selection with functional studies to
      demonstrate the physiologic impact of candidate loci.

PMID- 25383064
TI  - 3-D Localization Method for a Magnetically Actuated Soft Capsule Endoscope and
      Its Applications.
AB  - In this paper, we present a 3-D localization method for a magnetically actuated
      soft capsule endoscope (MASCE). The proposed localization scheme consists of
      three steps. First, MASCE is oriented to be coaxially aligned with an external
      permanent magnet (EPM). Second, MASCE is axially contracted by the enhanced
      magnetic attraction of the approaching EPM. Third, MASCE recovers its initial
      shape by the retracting EPM as the magnetic attraction weakens. The combination
      of the estimated direction in the coaxial alignment step and the estimated
      distance in the shape deformation (recovery) step provides the position of MASCE
      in 3-D. It is experimentally shown that the proposed localization method could
      provide 2.0-3.7 mm of distance error in 3-D. This study also introduces two new
      applications of the proposed localization method. First, based on the trace of
      contact points between the MASCE and the surface of the stomach, the 3-D
      geometrical model of a synthetic stomach was reconstructed. Next, the relative
      tissue compliance at each local contact point in the stomach was characterized by
      measuring the local tissue deformation at each point due to the preloading force.
      Finally, the characterized relative tissue compliance parameter was mapped onto
      the geometrical model of the stomach toward future use in disease diagnosis.

PMID- 25383065
TI  - West Nile Virus Activity in Kern County and the Factors Leading to the 2007
      Outbreak.
AB  - West Nile virus (WNV) reappeared in Kern County in late-May 2007, amplified
      rapidly and was detected concurrently by all surveillance methods. Enzootic
      activity during 2007 had some similarities to that of the previous three years,
      with 77 seropositive sentinel chickens in 9 flocks, 207 positive mosquito pools,
      124 dead birds that tested positive, and 168 seropositive wild birds. WNV disease
      in equines remained infrequent, with only 4 cases reported. In contrast, Kern
      County had a significant increase in human disease, with 138 laboratory confirmed
      fever and neuroinvasive cases, combined incidence = 17.8 per 100,000 population.
      The standard surveillance indicators, sentinel chickens and mosquito pools,
      indicated that WNV enzootic activity was on the decline, yet there were epidemic
      numbers of human cases. During this fourth year of virus activity, WNV was found
      throughout Kern County on the floor of the Central Valley.

PMID- 25383066
TI  - Scalable and Axiomatic Ranking of Network Role Similarity.
AB  - A key task in analyzing social networks and other complex networks is role
      analysis: describing and categorizing nodes according to how they interact with
      other nodes. Two nodes have the same role if they interact with equivalent sets
      of neighbors. The most fundamental role equivalence is automorphic equivalence.
      Unfortunately, the fastest algorithms known for graph automorphism are
      nonpolynomial. Moreover, since exact equivalence is rare, a more meaningful task
      is measuring the role similarity between any two nodes. This task is closely
      related to the structural or link-based similarity problem that SimRank
      addresses. However, SimRank and other existing similarity measures are not
      sufficient because they do not guarantee to recognize automorphically or
      structurally equivalent nodes. This paper makes two contributions. First, we
      present and justify several axiomatic properties necessary for a role similarity
      measure or metric. Second, we present RoleSim, a new similarity metric which
      satisfies these axioms and which can be computed with a simple iterative
      algorithm. We rigorously prove that RoleSim satisfies all these axiomatic
      properties. We also introduce Iceberg RoleSim, a scalable algorithm which
      discovers all pairs with RoleSim scores above a user-defined threshold theta. We
      demonstrate the interpretative power of RoleSim on both both synthetic and real
      datasets.

PMID- 25383067
TI  - Perceptions of an implantable cardioverter-defibrillator: A qualitative study of
      families with a history of sudden life-threatening cardiac events and
      recommendations to improve care.
AB  - OBJECTIVE: To identify major concerns associated with implantable cardioverter
      defibrillators (ICDs) and to provide recommendations to adult and pediatric
      physicians involved in the care of patients with ICDs. BACKGROUND: Cardiac ion
      channelopathies are a well-recognized cause of sudden cardiac death in infants,
      children, adolescents, and young adults. ICDs are effective in preventing sudden
      death from fatal arrhythmias in patients with known cardiac channelopathies.
      There is a paucity of research on the effect of ICDs on quality of life in
      patients with cardiac channelopathy diagnoses, especially young patients.
      METHODS: A qualitative study interviewing patients and families affected by
      inherited arrhythmias was conducted. Fifty participants with personal or family
      histories of cardiac events or sudden death were interviewed individually or in
      focus groups by clinical psychologists. All interviews were transcribed verbatim
      and then analyzed and coded based on current qualitative research theory to
      identify themes related to the research question. Twenty-four participants
      discussed ICDs in their interviews. RESULTS: Participants reported concerns about
      ICDs, and these concerns were categorized into six themes: (1) comprehension and
      physician-patient communication; (2) anxiety; (3) restrictions and fallacies; (4)
      complications; (5) utility; and (6) alternative therapy. Participants noted
      communication breakdowns between providers and their colleagues, and between
      providers and their patients. Participants and their families experienced many
      different forms of anxiety, including worry about the aesthetics of the ICDs and
      fears of being shocked. Multiple restrictions, fallacies, and complications were
      also cited. CONCLUSION: Interview themes were used to formulate recommendations
      for counseling and educating patients with ICDs.

PMID- 25383068
TI  - Deterministic Function Computation with Chemical Reaction Networks.
AB  - Chemical reaction networks (CRNs) formally model chemistry in a well-mixed
      solution. CRNs are widely used to describe information processing occurring in
      natural cellular regulatory networks, and with upcoming advances in synthetic
      biology, CRNs are a promising language for the design of artificial molecular
      control circuitry. Nonetheless, despite the widespread use of CRNs in the natural
      sciences, the range of computational behaviors exhibited by CRNs is not well
      understood. CRNs have been shown to be efficiently Turing-universal (i.e., able
      to simulate arbitrary algorithms) when allowing for a small probability of error.
      CRNs that are guaranteed to converge on a correct answer, on the other hand, have
      been shown to decide only the semilinear predicates (a multi-dimensional
      generalization of "eventually periodic" sets). We introduce the notion of
      function, rather than predicate, computation by representing the output of a
      function f : N k -> N l by a count of some molecular species, i.e., if the CRN
      starts with x1, ..., xk molecules of some "input" species X1, ..., Xk , the CRN
      is guaranteed to converge to having f(x1, ..., xk ) molecules of the "output"
      species Y1, ..., Yl . We show that a function f : N k -> N l is deterministically
      computed by a CRN if and only if its graph {(x, y) ? N k * N l ? f(x) = y} is a
      semilinear set. Finally, we show that each semilinear function f (a function
      whose graph is a semilinear set) can be computed by a CRN on input x in expected
      time O(polylog ?x?1).

PMID- 25383069
TI  - Electron tunneling pathways in respiratory complex I. The role of the internal
      water between the enzyme subunits.
AB  - Recently, the atomistic details of the electronic wiring of seven Fe/S clusters
      (N3, N1b, N4, N5, N6a, N6b, N2) of respiratory complex I, along which electrons
      are injected into the electron transport chain, have been revealed; the tunneling
      pathways between the clusters and the contributing key residues were identified
      [1]. In this study, the sensitivity of the electron tunneling pathways to the
      internal water at the protein subunit boundaries is investigated by simulating
      tunneling pathways of N3->N1b and N6b->N2 with and without the internal water. It
      is found that the hydrogen bonding networks formed along the internal water can
      provide efficient tunneling pathways. In N3->N1b, the tunneling pathway with the
      internal water is drastically different with significantly shorter (3.4 A) total
      tunneling distance along the trajectory. In N6b->N2, the internal water
      contributes to the tunneling as a bridge between N6b and 9Ile99 with two shorter
      through-space jumps instead of one longer jump. The resulting enhancement of the
      rates of the individual electron tunneling process is two to three orders of
      magnitude. This study demonstrates that the tunneling pathways and tunneling
      rates are sensitive to the internal water, which suggests that the tunneling
      pathways can change dynamically due to the diffusion of the internal water, and
      that the efficient electron tunneling occurs at some specific optimal positions
      of the internal water.

PMID- 25383071
TI  - 1H NMR Metabolomics Study of Metastatic Melanoma in C57BL/6J Mouse Spleen.
AB  - Melanoma is a malignant tumor of melanocytes. Although extensive investigations
      have been done to study metabolic changes in primary melanoma in vivo and in
      vitro, little effort has been devoted to metabolic profiling of metastatic tumors
      in organs other than lymph nodes. In this work, NMR-based metabolomics combined
      with multivariate data analysis is used to study metastatic B16-F10 melanoma in
      C57BL/6J mouse spleen. Principal Component Analysis (PCA), an unsupervised
      multivariate data analysis method, is used to detect possible outliers, while
      Orthogonal Projection to Latent Structure (OPLS), a supervised multivariate data
      analysis method, is employed to find important metabolites responsible for
      discriminating the control and the melanoma groups. Two different strategies,
      i.e. spectral binning and spectral deconvolution, are used to reduce the original
      spectral data before statistical analysis. Spectral deconvolution is found to be
      superior for identifying a set of discriminatory metabolites between the control
      and the melanoma groups, especially when the sample size is small. OPLS results
      show that the melanoma group can be well separated from its control group. It is
      found that taurine, glutamate, aspartate, O-Phosphoethanolamine, niacinamide,ATP,
      lipids and glycerol derivatives are decreased statistically and significantly
      while alanine, malate, xanthine, histamine, dCTP, GTP, thymidine, 2'
      Deoxyguanosine are statistically and significantly elevated. These significantly
      changed metabolites are associated with multiple biological pathways and may be
      potential biomarkers for metastatic melanoma in spleen.

PMID- 25383070
TI  - Microbes in Beach Sands: Integrating Environment, Ecology and Public Health.
AB  - Beach sand is a habitat that supports many microbes, including viruses, bacteria,
      fungi and protozoa (micropsammon). The apparently inhospitable conditions of
      beach sand environments belie the thriving communities found there. Physical
      factors, such as water availability and protection from insolation; biological
      factors, such as competition, predation, and biofilm formation; and nutrient
      availability all contribute to the characteristics of the micropsammon. Sand
      microbial communities include autochthonous species/phylotypes indigenous to the
      environment. Allochthonous microbes, including fecal indicator bacteria (FIB) and
      waterborne pathogens, are deposited via waves, runoff, air, or animals. The fate
      of these microbes ranges from death, to transient persistence and/or replication,
      to establishment of thriving populations (naturalization) and integration in the
      autochthonous community. Transport of the micropsammon within the habitat occurs
      both horizontally across the beach, and vertically from the sand surface and
      ground water table, as well as at various scales including interstitial flow
      within sand pores, sediment transport for particle-associated microbes, and the
      large-scale processes of wave action and terrestrial runoff. The concept of beach
      sand as a microbial habitat and reservoir of FIB and pathogens has begun to
      influence our thinking about human health effects associated with sand exposure
      and recreational water use. A variety of pathogens have been reported from beach
      sands, and recent epidemiology studies have found some evidence of health risks
      associated with sand exposure. Persistent or replicating populations of FIB and
      enteric pathogens have consequences for watershed/beach management strategies and
      regulatory standards for safe beaches. This review summarizes our understanding
      of the community structure, ecology, fate, transport, and public health
      implications of microbes in beach sand. It concludes with recommendations for
      future work in this vastly under-studied area.

PMID- 25383072
TI  - Do you see what I see: Recognition of protozoan parasites by Toll-like receptors.
AB  - Toll-like receptors (TLRs) are important for recognizing a variety of pathogens,
      including protozoan parasites, and initiating innate immune responses against
      them. TLRs are localized on the cell surface as well as in the endosome, and are
      implicated in innate sensing of these parasites. In this review, we will discuss
      recent findings on the identification of parasite-derived pathogen associated
      molecular patterns and the TLRs that bind them. The role of these TLRs in
      initiating the immune response against protozoan parasitic infections in vivo
      will be presented in the context of murine models of infection utilizing TLR
      deficient mice. Additionally, we will explore evidence that TLRs and genetic
      variants of TLRs may impact the outcome of these parasitic infections in humans.

PMID- 25383075
TI  - Validity Concerns with Multiplying Ordinal Items Defined by Binned Counts: An
      Application to a Quantity-Frequency Measure of Alcohol Use.
AB  - Social and behavioral scientists often measure constructs that are truly discrete
      counts by collapsing (or binning) the counts into a smaller number of ordinal
      responses. While prior quantitative research has identified a series of concerns
      with similar binning procedures, there has been a lack of study on the
      consequences of multiplying these ordinal items to create a desired index. This
      measurement strategy is incorporated in many research applications, but it is
      particularly salient in the study of substance use where the product of ordinal
      quantity (number of drinks) and frequency (number of days) items is used to
      create an index of total consumption. In the current study, we demonstrate both
      analytically and empirically that this multiplicative procedure can introduce
      serious threats to construct validity. These threats, in turn, directly impact
      the ability to accurately measure alcohol consumption.

PMID- 25383074
TI  - The Future of D-Cycloserine and Other Cognitive Modifiers in Obsessive-Compulsive
      and Related Disorders.
AB  - Variants of exposure therapy are effective for treating obsessive-compulsive and
      related disorders (OCRDs). However, significant numbers of patients do not
      respond adequately to exposure therapy resulting in continued distress and
      functional impairment. Therefore, novel approaches to augmenting exposure therapy
      are needed to adequately treat non- and partial-responders. Emerging research
      suggests that interventions that augment learning and memory processes associated
      with exposure therapy (i.e., extinction training) may display promise in
      enhancing treatment response in OCRDs. As the most studied example, d-cycloserine
      (DCS) is a relatively safe cognitive enhancer that appears to accelerate
      treatment gains associated with exposure therapy. This article reviews research
      on the use of DCS and other putative cognitive modifiers as they relate to the
      treatment (or prospective treatment) of obsessive-compulsive disorder and other
      OCRDs.

PMID- 25383076
TI  - Dynamic Electrochemical Membranes for Continuous Affinity Protein Separation.
AB  - A membrane system with nm-scale thick electrodes is able to selectively bind
      genetically modified proteins and pump them across the membrane with sequential
      voltage pulses. The electrodes are located at the first 20nm of pore entrances to
      specifically capture targeted proteins and block non-specific protein transport
      through the pores during the binding cycle. During the release cycle,
      concentration of imidazole is controlled to keep the pore blocked while releasing
      proteins at the bottom edge of the electrode. A separation factor for GFP:BSA of
      16 was achieved with observed GFP electrophoretic mobility of 2.54*10-6cm2v-1S-1.
      This non-optimized system with a membrane area of 0.75 cm2 has the same
      throughput as 1ml of commercially available chromatography columns showing
      viability as a continuous process. This system will enable continuous separation
      of expressed proteins directly from fermentation broths dramatically simplifying
      the separation process as well as reducing biopharmaceutical production costs.

PMID- 25383073
TI  - Role of Chemokines and Trafficking of Immune Cells in Parasitic Infections.
AB  - Parasites are diverse eukaryotic pathogens that can have complex life cycles.
      Their clearance, or control within a mammalian host requires the coordinated
      effort of the immune system. The cell types recruited to areas of infection can
      combat the disease, promote parasite replication and survival, or contribute to
      disease pathology. Location and timing of cell recruitment can be crucial. In
      this review, we explore the role chemokines play in orchestrating and balancing
      the immune response to achieve optimal control of parasite replication without
      promoting pathology.

PMID- 25383077
TI  - Bioaccumulation, Sub-acute Toxicity, and Tissue Distribution of Engineered
      Titanium Dioxide (TiO2) Nanoparticles in Goldfish (Carassius auratus).
AB  - The increased use of nano-sized materials is likely to result in the release of
      these particles into the environment. It is, however, unclear if these materials
      are harmful to aquatic animals. In this study, the sub-lethal effects of exposure
      of low and high concentrations of titanium dioxide nanoparticles (TiO2 NPs) on
      goldfish (Carassius auratus) were investigated. Tissues, including intestine,
      gills, muscle, and brain were analyzed for Ti content by ICP-MS. Accumulation of
      TiO2 NPs increased from 42.71 to 110.68 ppb in the intestine and from 4.10 to
      9.86 ppb in the gills of the goldfish with increasing exposure dose from 10 to
      100 mg/L TiO2 NPs. No significant accumulation in the muscle and brain of the
      fish was detected. Malondialdehyde (MDA) as a biomarker of lipid oxidation was
      detected in the liver of the goldfish. Moreover, TiO2 NPs exposure inhibited
      growth of the goldfish. Although there was an increase (8.1%) in the body weights
      of the goldfish for the control group, in the low and high exposure groups 1.8%
      increase and 19.7 % decrease were measured respectively.

PMID- 25383078
TI  - Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in
      Bronchoalveolar Lavage.
AB  - We present the results of bronchoalveolar lavage (BAL) performed in three
      patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory
      distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates
      showed the presence of characteristic large, mononuclear,
      plasmoblastic/plasmocytoid-like cells never described before. Via transmission
      electron microscopy, these cells were classified as atypical type II pneumocytes
      and some of them showed cytoplasmic vesicles and inclusions. We concluded that
      plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic
      marker of A/H1N1 influenza virus infection as well as reparative cellular
      activation after diffuse alveolar damage. 

PMID- 25383079
TI  - 10th anniversary of allergy, asthma & clinical immunology.

PMID- 25383080
TI  - Blood in a dish: In vitro synthesis of red blood cells.
AB  - Red blood cells, currently obtained from donors, represent the most common form
      of cell-based therapy. A better understanding of normal erythropoiesis is leading
      to improved multi-step protocols for the in vitro generation of fully mature red
      cells. The extensive in vitro expansion of embryonic erythroblasts and
      development of erythroid precursors as a potential transfusion product may help
      to deal with issues of scale and eventually find a place in the treatment of
      patients with acute and chronic anemias.

PMID- 25383081
TI  - Current studies of acupuncture in cancer-induced bone pain animal models.
AB  - Acupuncture is generally accepted as a safe and harmless treatment option for
      alleviating pain. To explore the pain mechanism, numerous animal models have been
      developed to simulate specific human pain conditions, including cancer-induced
      bone pain (CIBP). In this study, we analyzed the current research methodology of
      acupuncture for the treatment of CIBP. We electronically searched the PubMed
      database for animal studies published from 2000 onward using these search terms:
      (bone cancer OR cancer) AND (pain OR analgesia) AND (acupuncture OR
      pharmacopuncture OR bee venom). We selected articles that described cancer pain
      in animal models. We analyzed the methods used to induce cancer pain and the
      outcome measures used to assess the effects of acupuncture on CIBP in animal
      models. We reviewed articles that met our inclusion criteria. Injection of
      mammary cancer cells into the cavity of the tibia was the most frequently used
      method for inducing CIBP in the animal models. Among the eight selected studies,
      five studies demonstrated the effects of electroacupuncture on CIBP. The effects
      of acupuncture were assessed by measuring pain-related behavior. Future
      researches will be needed to ascertain the effectiveness of acupuncture for
      treating CIBP and to explore the specific mechanism of CIBP in animal models. 

PMID- 25383082
TI  - The immunological enhancement activity of propolis flavonoids liposome in vitro
      and in vivo.
AB  - The aim of this study was to investigate and assess the effects of propolis
      flavonoids liposome imposed on the immune system by comparing it to propolis
      flavonoids and blank liposome. In vitro, the effects of the above drugs on
      macrophages were assessed by measuring the phagocytic function and cytokine
      production. In vivo, the immunological adjuvant activity of propolis flavonoids
      liposome was compared with those of propolis flavonoids and blank liposome. The
      results showed that in vitro propolis flavonoids liposome can significantly
      enhance the phagocytic function of macrophages and the release of IL-1beta, IL-6,
      and IFN-gamma. In addition, subcutaneous administration of propolis flavonoids
      liposome with ovalbumin to mice could effectively activate the cellular and
      humoral immune response, including inducing higher level concentrations of IgG,
      IL-4, and IFN-gamma in serum and the proliferation rates of splenic lymphocytes.
      These findings provided valuable information regarding the immune modulatory
      function of propolis flavonoids liposome and indicated the possibility of use of
      propolis flavonoids liposome as a potential adjuvant. 

PMID- 25383083
TI  - Effects of Temperature on Chronic Trapezius Myofascial Pain Syndrome during Dry
      Needling Therapy.
AB  - The purpose of this study was to investigate the effects of temperature on
      chronic trapezius myofascial pain syndrome during dry needling therapy. Sixty
      patients were randomized into two groups of dry needling (DN) alone (group A) and
      DN combined with heat therapy group (group B). Each patient was treated once and
      the therapeutic effect was assessed by the visual analogue scale (VAS), pressure
      pain threshold (PPT), and the 36-item short form health survey (SF-36) at seven
      days, one month, and three months after treatment. Evaluation based on VAS and
      PPT showed that the pain of patients in groups A and B was significantly (P <
      0.05) relieved at seven days, one month, and three months after treatment
      Compared to before treatment. There was significantly (P < 0.05) less pain in
      group B than group A at one and three months after treatment. The SF-36
      evaluation demonstrated that the physical condition of patients in both groups
      showed significant (P < 0.05) improvement at one month and three months after
      treatment than before treatment. Our study suggests that both DN and DN heating
      therapy were effective in the treatment of trapezius MPS, and that DN heating
      therapy had better long-term effects than DN therapy. 

PMID- 25383084
TI  - The Effects of Uygur Herb Hyssopus officinalis L. on the Process of Airway
      Remodeling in Asthmatic Mice.
AB  - It has been proved that Uygur herb Hyssopus offcinalis L. could affect the levels
      of some cytokines (such as IL-4, IL-6, IL-17, and IFN-gamma) in asthmatic mice.
      By detection of the expressions of MMP-9 and TIMP-1 and the morphological
      changes, the aim of this research is to reveal the mechanism of Uygur herb
      Hyssopus offcinalis L. in the process of airway remodeling. It was observed that
      the expressions of MMP-9 and TIMP-1 increased, but the ratio of MMP-9/TIMP-1
      decreased in airway remodeling group. However, the expression of both MMP-9 and
      TIMP-1 decreased after being treated with dexamethasone and Hyssopus offcinalis
      L., accompanied by the relieved pathological changes, including collagen
      deposition, mucus secretion, and smooth muscle proliferation. It is suggested
      that Uygur herb Hyssopus offcinalis L. could inhibit airway remodeling by
      correcting imbalance of MMP-9/TIMP-1 ratio. 

PMID- 25383085
TI  - Approaches to accommodate noisy data in the direct solution of inverse problems
      in incompressible plane-strain elasticity.
AB  - We apply the adjoint weighted equation method (AWE) to the direct solution of
      inverse problems of incompressible plane strain elasticity. We show that based on
      untreated noisy displacements, the reconstruction of the shear modulus can be
      very poor. We link this poor performance to loss of coercivity of the weak form
      when treating problems with discontinuous coefficients. We demonstrate that by
      smoothing the displacements and appending a regularization term to the AWE
      formulation, a dramatic improvement in the reconstruction can be achieved. With
      these improvements, the advantages of the AWE method as a direct solution
      approach can be extended to a wider range of problems.

PMID- 25383086
TI  - Predicted optical performance of the GM/CA@APS micro-focus beamline.
AB  - GM/CA at the APS has developed microcrystallography capabilities for structural
      biology applications. The robust, quad, mini-beam collimators, which enable users
      to rapidly select between a 5, 10 or 20 micron diameter beam or a scatter guard
      for the full focused beam, are coupled with several powerful automated software
      tools that are built into the beamline control system JBluIce-EPICS. Recent
      successes at beamlines around the world in solving structures from microcrystals
      (2 - 10 microns) have led to increased demand for high-intensity micro-focus
      beams. We have designed a new micro-focus endstation to increase the intensity in
      mini- and micro-beams at GM/CA by one to two orders of magnitude to meet this
      growing demand. The new optical design is based on the well-established approach
      of using two-stage demagnification. The existing bimorph mirrors, arranged in a
      Kirkpatrick-Baez geometry, focus the beam onto slits located upstream of the
      sample whereby the slit aperture defines a secondary source, that is reimaged
      with a second pair of mirrors. This design incorporates two focal modes: a mini
      beam mode where the beam is focused to 20-micron diameter and a micro-beam mode
      where it is focused to 5-microns. The size of the secondary source aperture can
      be varied rapidly (seconds) to adjust the beam size at the sample position in two
      ranges 20 - 3 micron and 5 - 1 micron. The second set of mirrors will each have
      two super polished ellipses allowing quick (minutes) interchange between modes.

PMID- 25383087
TI  - Hemifusion of giant unilamellar vesicles with planar hydrophobic surfaces: a
      fluorescence microscopy study.
AB  - Vesicle adhesion and fusion to interfaces are frequently used for the
      construction of biomimetic surfaces in biosensors and drug delivery. Ubiquitous
      in cell biology, vesicle fusion involves the transformation of two separate
      membranes into one contiguous lipid bilayer. In distinction, the deposition of
      vesicle membranes to hydrophobic surfaces requires the transformation of a
      lipidic bilayer into a monomolecular layer - a topologically distinct process
      termed hemifusion. Here, we used hydrophobically terminated self-assembled
      monolayers (SAMs) on solid surfaces to track the hemifusion of fluorescently
      labeled giant unilamellar vesicles (GUVs) at the single vesicle level with video
      time resolution (~53 ms). We observed that a dilute monolayer, consisting of
      lipid extracted from the outer GUV leaflet, spreads outward across the
      hydrophobic surface from the vesicle adhesion site. Subsequently, bilayer
      hemifusion occurs by vesicle rupture near the hydrophobic surface, followed by
      spreading of lipid in a dense monolayer. GUV lipids thus transfer to the SAM
      surface in two concentric zones: an outer hemifusion zone comprises lipids drawn
      from the outer GUV leaflet and an inner hemifusion zone comprises lipids from
      both the inner and outer GUV leaflets and grows at a rate of ~1000 um2 s-1 (dA/dt
      = 970 +/- 430 um2 s-1 in n = 22 independent experiments). This growth rate is
      quantitatively consistent with the assumption that the spreading of the monolayer
      is entirely driven by the difference in surface energies of the hydrophobic and
      the lipid-covered SAM surfaces, which is dissipated by friction of the spreading
      monolayer on the SAM. Lipid transfer between the inner and outer GUV leaflets
      occurs via a hemifusion pore that forms early in the process near the membrane
      contact site. This pore also permits expulsion of water from the GUV interior as
      the vesicle contracts onto the contact site.

PMID- 25383088
TI  - Soft Polymer Magnetic Nanocomposites: Microstructure Patterning by
      Magnetophoretic Transport and Self-Assembly.
AB  - A method to produce and pattern magnetic microstructure in a soft-polymer matrix
      is demonstrated. An externally applied magnetic field is used to influence the
      dynamics of magnetophoretic transport and dipolar self-assembly of magnetic
      nanoparticle clusters in the liquid precursor of poly-dimethylsiloxane (PDMS).
      Magnetic nanoparticles agglomerate by an interplay of van der Waals forces and
      dipolar interactions to form anisotropic clusters. These clusters are
      concentrated on a substrate by magnetophoresis, wherein they self-organize by
      dipolar interactions to form microscopic filaments. The polymer is cured in the
      presence of the magnetic field to preserve the microstructure shape. The
      externally applied magnetic field and its gradient are the two main control
      variables of interest when considering magnetic control during nanoparticle self
      assembly. Their influence on microstructure geometry is investigated through
      correlations with the height of a characteristic self-assembled filament,
      fraction of the substrate area covered by the microstructure and its shape
      anisotropy. These relations enable a priori design.

PMID- 25383090
TI  - Isotropic 3D Super-resolution Imaging with a Self-bending Point Spread Function.
AB  - Airy beams maintain their intensity profiles over a large propagation distance
      without substantial diffraction and exhibit lateral bending during propagation1
      5. This unique property has been exploited for micromanipulation of particles6,
      generation of plasma channels7 and guidance of plasmonic waves8, but has not been
      explored for high-resolution optical microscopy. Here, we introduce a self
      bending point spread function (SB-PSF) based on Airy beams for three-dimensional
      (3D) super-resolution fluorescence imaging. We designed a side-lobe-free SB-PSF
      and implemented a two-channel detection scheme to enable unambiguous 3D
      localization of fluorescent molecules. The lack of diffraction and the
      propagation-dependent lateral bending make the SB-PSF well suited for precise 3D
      localization of molecules over a large imaging depth. Using this method, we
      obtained super-resolution imaging with isotropic 3D localization precision of 10
      15 nm over a 3 MUm imaging depth from ~2000 photons per localization.

PMID- 25383091
TI  - The HAC trial (harmonic for acute cholecystitis): a randomized, double-blind,
      controlled trial comparing the use of harmonic scalpel to monopolar diathermy for
      laparoscopic cholecystectomy in cases of acute cholecystitis.
AB  - BACKGROUND: The HARMONIC SCALPEL (H) is an advanced ultrasonic cutting and
      coagulating surgical device with important clinical advantages, such as: reduced
      ligature demand; greater precision due to minimal lateral thermal tissue damage;
      minimal smoke production; absence of electric corrents running through the
      patient. However, there are no prospective RCTs demonstrating the advantages of H
      compared to the conventional monopolar diathermy (MD) during laparoscopic
      cholecystectomy (LC) in cases of acute cholecystitis (AC). METHODS: This study
      was a prospective, single-center, randomized trial (Trial Registration Number:
      NCT00746850) designed to investigate whether the use of H can reduce the
      incidence of intra-operative conversion during LC in cases of AC, compared to the
      use of MD. Patients were divided into two groups: both groups underwent early LC,
      within 72 hours of diagnosis, using H and MD respectively (H = experimental/study
      group, MD = control group). The study was designed and conducted in accordance
      with the regulations of Good Clinical Practice. RESULTS: 42 patients were
      randomly assigned the use of H (21 patients) or MD (21 patients) during LC. The
      two groups were comparable in terms of basic patient characteristics. Mean
      operating time in the H group was 101.3 minutes compared to 106.4 minutes in the
      control group (p=ns); overall blood loss was significantly lower in the H group.
      Conversion rate was 4.7% for the H group, which was significantly lower than the
      33% conversion rate for the control group (p<0.05). Post-operative morbidity
      rates differed slightly: 19% and 23% in the H and control groups, respectively
      (p=ns). Average post-operative hospitalization lasted 5.2 days in the H group
      compared to 5.4 days in the control group (p=ns). CONCLUSIONS: The use of H
      appears to correlate with reduced rates of laparoscopic-open conversion. Given
      this evidence, H may be more suitable than MD for technically demanding cases of
      AC.

PMID- 25383089
TI  - Calcineurin as a Multifunctional Regulator: Unraveling Novel Functions in Fungal
      Stress Responses, Hyphal Growth, Drug Resistance, and Pathogenesis.
AB  - Calcineurin signaling plays diverse roles in fungi in regulating stress
      responses, morphogenesis and pathogenesis. Although calcineurin signaling is
      conserved among fungi, recent studies indicate important divergences in
      calcineurin-dependent cellular functions among different human fungal pathogens.
      Fungal pathogens utilize the calcineurin pathway to effectively survive the host
      environment and cause life-threatening infections. The immunosuppressive
      calcineurin inhibitors (FK506 and cyclosporine A) are active against fungi,
      making targeting calcineurin a promising antifungal drug development strategy.
      Here we summarize current knowledge on calcineurin in yeasts and filamentous
      fungi, and review the importance of understanding fungal-specific attributes of
      calcineurin to decipher fungal pathogenesis and develop novel antifungal
      therapeutic approaches.

PMID- 25383092
TI  - Genetic diversity and population structure of Rheum tanguticum (Dahuang) in
      China.
AB  - BACKGROUND: Wild Rheum tanguticum (Dahuang in Chinese) has becoming endangered in
      China. This study aims to examine the genetic structure and genetic diversity of
      R. tanguticum within species, and the genetic differentiation within and among
      populations in China. METHODS: The variability and structure of 19 populations of
      R. tanguticum were investigated by their chloroplast DNA matK sequences. The
      genetic diversity index was calculated by Dnasp, PERMUT, and Arlequin 3.0
      software, and a neighbor-joining (NJ)-tree was constructed by MEGA 5.0 software.
      RESULTS: Fifteen haplotypes were obtained based on the matK sequence analysis.
      The mean genetic diversity within species was 0.894, and the genetic variability
      among populations (67.6%) was relatively higher than that within populations
      (13.88%) according to the AMOVA and PERMUT analyses. The NJ-tree and a pairwise
      difference analysis indicated geographical isolation of R. tanguticum. The gene
      flow among populations was 0.05, indicating a genetic drift among some
      populations, which was also confirmed by the NJ-tree and haplotype distributions.
      Furthermore, a mismatch distribution analysis revealed the molecular evolution of
      R. tanguticum. CONCLUSION: Genetic diversity among and within populations of R.
      tanguticum in China was demonstrated.

PMID- 25383093
TI  - Large area micropatterning of cells on polydimethylsiloxane surfaces.
AB  - BACKGROUND: Precise spatial control and patterning of cells is an important area
      of research with numerous applications in tissue engineering, as well as
      advancing an understanding of fundamental cellular processes. Poly (dimethyl
      siloxane) (PDMS) has long been used as a flexible, biocompatible substrate for
      cell culture with tunable mechanical characteristics. However, fabrication of
      suitable physico-chemical barriers for cells on PDMS substrates over large areas
      is still a challenge. RESULTS: Here, we present an improved technique which
      integrates photolithography and cell culture on PDMS substrates wherein the
      barriers to cell adhesion are formed using the photo-activated graft
      polymerization of polyethylene glycol diacrylate (PEG-DA). PDMS substrates with
      varying stiffness were prepared by varying the base to crosslinker ratio from 5:1
      to 20:1. All substrates show controlled cell attachment confined to fibronectin
      coated PDMS microchannels with a resistance to non-specific adhesion provided by
      the covalently immobilized, hydrophilic PEG-DA. CONCLUSIONS: Using
      photolithography, it is possible to form patterns of high resolution stable at 37
      degrees C over 2 weeks, and microstructural complexity over large areas of a few
      cm(2). As a robust and scalable patterning method, this technique showing
      homogenous and stable cell adhesion and growth over macroscales can bring
      microfabrication a step closer to mass production for biomedical applications.

PMID- 25383095
TI  - Measuring bias in self-reported data.
AB  - Response bias shows up in many fields of behavioural and healthcare research
      where self-reported data are used. We demonstrate how to use stochastic frontier
      estimation (SFE) to identify response bias and its covariates. In our application
      to a family intervention, we examine the effects of participant demographics on
      response bias before and after participation; gender and race/ethnicity are
      related to magnitude of bias and to changes in bias across time, and bias is
      lower at post-test than at pre-test. We discuss how SFE may be used to address
      the problem of 'response shift bias' - that is, a shift in metric from before to
      after an intervention which is caused by the intervention itself and may lead to
      underestimates of programme effects.

PMID- 25383094
TI  - The role of complement in the pathogenesis of renal ischemia-reperfusion injury
      and fibrosis.
AB  - The complement system is a major component of innate immunity and has been
      commonly identified as a central element in host defense, clearance of immune
      complexes, and tissue homeostasis. After ischemia-reperfusion injury (IRI), the
      complement system is activated by endogenous ligands that trigger proteolytic
      cleavage of complement components via the classical, lectin and/or alternative
      pathway. The result is the formation of terminal complement components C3a, C5a,
      and the membrane attack complex (C5b-9 or MAC), all of which play pivotal roles
      in the amplification of the inflammatory response, chemotaxis,
      neutrophil/monocyte recruitment and activation, and direct tubular cell injury.
      However, recent evidence suggests that complement activity transcends innate host
      defense and there is increasing data suggesting complement as a regulator in
      processes such as allo-immunity, stem cell differentiation, tissue repair, and
      progression to fibrosis. In this review, we discuss recent advances addressing
      the role of complement as a regulator of IRI and renal fibrosis after organ
      donation for transplantation. We will also briefly discuss currently approved
      therapies that target complement activity in kidney ischemia-reperfusion and
      transplantation. 

PMID- 25383096
TI  - Applications of the MapReduce programming framework to clinical big data
      analysis: current landscape and future trends.
AB  - The emergence of massive datasets in a clinical setting presents both challenges
      and opportunities in data storage and analysis. This so called "big data"
      challenges traditional analytic tools and will increasingly require novel
      solutions adapted from other fields. Advances in information and communication
      technology present the most viable solutions to big data analysis in terms of
      efficiency and scalability. It is vital those big data solutions are
      multithreaded and that data access approaches be precisely tailored to large
      volumes of semi-structured/unstructured data. THE MAPREDUCE PROGRAMMING FRAMEWORK
      USES TWO TASKS COMMON IN FUNCTIONAL PROGRAMMING: Map and Reduce. MapReduce is a
      new parallel processing framework and Hadoop is its open-source implementation on
      a single computing node or on clusters. Compared with existing parallel
      processing paradigms (e.g. grid computing and graphical processing unit (GPU)),
      MapReduce and Hadoop have two advantages: 1) fault-tolerant storage resulting in
      reliable data processing by replicating the computing tasks, and cloning the data
      chunks on different computing nodes across the computing cluster; 2) high
      throughput data processing via a batch processing framework and the Hadoop
      distributed file system (HDFS). Data are stored in the HDFS and made available to
      the slave nodes for computation. In this paper, we review the existing
      applications of the MapReduce programming framework and its implementation
      platform Hadoop in clinical big data and related medical health informatics
      fields. The usage of MapReduce and Hadoop on a distributed system represents a
      significant advance in clinical big data processing and utilization, and opens up
      new opportunities in the emerging era of big data analytics. The objective of
      this paper is to summarize the state-of-the-art efforts in clinical big data
      analytics and highlight what might be needed to enhance the outcomes of clinical
      big data analytics tools. This paper is concluded by summarizing the potential
      usage of the MapReduce programming framework and Hadoop platform to process huge
      volumes of clinical data in medical health informatics related fields. 

PMID- 25383097
TI  - A generalizable definition of chemical similarity for read-across.
AB  - BACKGROUND: Methods that provide a measure of chemical similarity are strongly
      relevant in several fields of chemoinformatics as they allow to predict the
      molecular behavior and fate of structurally close compounds. One common
      application of chemical similarity measurements, based on the principle that
      similar molecules have similar properties, is the read-across approach, where an
      estimation of a specific endpoint for a chemical is provided using experimental
      data available from highly similar compounds. RESULTS: This paper reports the
      comparison of multiple combinations of binary fingerprints and similarity metrics
      for computing the chemical similarity in the context of two different
      applications of the read-across technique. CONCLUSIONS: Our analysis demonstrates
      that the classical similarity measurements can be improved with a generalizable
      model of similarity. The proposed approach has already been used to build
      similarity indices in two open-source software tools (CAESAR and VEGA) that make
      several QSAR models available. In these tools, the similarity index plays a key
      role for the assessment of the applicability domain.

PMID- 25383098
TI  - A molecular fragment cheminformatics roadmap for mesoscopic simulation.
AB  - BACKGROUND: Mesoscopic simulation studies the structure, dynamics and properties
      of large molecular ensembles with millions of atoms: Its basic interacting units
      (beads) are no longer the nuclei and electrons of quantum chemical ab-initio
      calculations or the atom types of molecular mechanics but molecular fragments,
      molecules or even larger molecular entities. For its simulation setup and output
      a mesoscopic simulation kernel software uses abstract matrix (array)
      representations for bead topology and connectivity. Therefore a pure kernel-based
      mesoscopic simulation task is a tedious, time-consuming and error-prone venture
      that limits its practical use and application. A consequent cheminformatics
      approach tackles these problems and provides solutions for a considerably
      enhanced accessibility. This study aims at outlining a complete cheminformatics
      roadmap that frames a mesoscopic Molecular Fragment Dynamics (MFD) simulation
      kernel to allow its efficient use and practical application. RESULTS: The
      molecular fragment cheminformatics roadmap consists of four consecutive building
      blocks: An adequate fragment structure representation (1), defined operations on
      these fragment structures (2), the description of compartments with defined
      compositions and structural alignments (3), and the graphical setup and analysis
      of a whole simulation box (4). The basis of the cheminformatics approach (i.e.
      building block 1) is a SMILES-like line notation (denoted fSMILES) with connected
      molecular fragments to represent a molecular structure. The fSMILES notation and
      the following concepts and methods for building blocks 2-4 are outlined with
      examples and practical usage scenarios. It is shown that the requirements of the
      roadmap may be partly covered by already existing open-source cheminformatics
      software. CONCLUSIONS: Mesoscopic simulation techniques like MFD may be
      considerably alleviated and broadened for practical use with a consequent
      cheminformatics layer that successfully tackles its setup subtleties and
      conceptual usage hurdles. Molecular Fragment Cheminformatics may be regarded as a
      crucial accelerator to propagate MFD and similar mesoscopic simulation techniques
      in the molecular sciences. Graphical abstractA molecular fragment cheminformatics
      roadmap for mesoscopic simulation.

PMID- 25383099
TI  - Correlation between reduction of superior interventricular groove epicardial fat
      thickness and improvement of insulin resistance after weight loss in obese men.
AB  - BACKGROUND: It has been recognized that reduction of abdominal visceral fat and
      subcutaneous fat are associated with improvement in insulin-resistance (IR) after
      weight loss. However, few studies have investigated the correlation of reduction
      in epicardial adipose tissue (EAT) with improvement of IR index after weight loss
      in obese non-diabetic men with metabolic syndrome (MetS). METHODS AND RESULTS: We
      prospectively enrolled 32 non-diabetic men with MetS for a 3-month weight
      reduction program mainly by diet control and exercise. Magnetic resonance imaging
      (MRI) examinations were used to measure EAT, subcutaneous fat, and abdominal
      visceral fat. Anthropometric parameters, oral glucose tolerance test (OGTT), and
      serum adipokines were assessed before and after the weight loss program. After a
      3-month weight loss program, 27 obese MetS men had significant weight loss >5%
      (97 +/- 14 to 87 +/- 14 kg, with a 10.7 % decrease, p < 0.001). Multivariate
      analysis revealed that the decrement ratio of superior interventricular groove
      (SIVG) EAT thickness (r = 0.322, p = 0.044) and serum leptin (r = 0.626, p <
      0.001) significantly correlated with the percentage improvements of fasting HOMA
      IR index. Furthermore, the decrement ratio of SIVG EAT thickness (r = -0.370, p =
      0.017) and decrement ratio of subcutaneous fat area (r = -0.673, p = 0.006) were
      significantly correlated with improvement of OGTT-derived Matsuda insulin
      sensitivity index. CONCLUSIONS: The decrement ratio of SIVG EAT correlated with
      improvement of both HOMA-IR and OGTT-derived Matsuda insulin-sensitivity indexes
      after weight loss in obese non-diabetic men with MetS. CLINICAL TRIAL
      REGISTRATION: (Multi-faceted Evaluations Following Weight Reduction in Subjects
      with Metabolic Syndrome NCT 01065753 on Feb 8, 2010).

PMID- 25383100
TI  - Synthesis and characterization of perfluoro-tert-butyl semifluorinated
      amphiphilic polymers and their potential application in hydrophobic drug
      delivery.
AB  - Semifluorinated polymer surfactants, composed of a monomethyl poly(ethylene
      glycol) (mPEG) hydrophilic head group and either 1, 2, or 3 perfluoro-tert-butyl
      (PFtB) groups as the fluorophilic tail, were synthesized, and their aqueous self
      assemblies were investigated as a potential design for theranostic nanoparticles.
      Polymers with three PFtB groups (PFtBTRI) solely formed stable, spherical
      micelles, approximately 12 nm in size. These PFtBTRI surfactants demonstrate
      similar characteristics with those of polymers with linear perfluorocarbon tails,
      despite large differences in tail structure. For example, PFtB polymer solutions
      stably emulsified 20 v/v% sevoflurane with perfluorooctyl bromide (PFOB) as a
      stabilizer. However, these PFtB polymers have the additional potential to serve
      as F-MRI contrast agents. PFtBTRI micelles gave one narrow 19F-NMR signal in D2O,
      with T1 and T2 parameters of approximately 500 and 100 ms, respectively. 19F-MR
      images of PFtB polymer solutions at 1 mM gave intense signal at 4.7 T without
      sensitizers or selective excitation sequences. These preliminary data demonstrate
      the potential of PFtB polymers as a basic design, which can be further modified
      to serve as dual drug-delivery and imaging vehicles.

PMID- 25383101
TI  - NANOPATTERNED INTERFACES FOR CONTROLLING CELL BEHAVIOR.
AB  - Many studies have demonstrated that microscale changes to surface chemistry and
      topography affect cell adhesion, proliferation, differentiation, and gene
      expression. More recently, studies have begun to examine cell behavior
      interactions with structures on the nanoscale since in vivo, cells recognize and
      adhere to cell adhesion receptors that are spatially organized on this scale.
      These studies have been enabled through various fabrication methods, many of
      which were initially developed for the semiconductor industry. This review
      explores cell responses to a variety of controlled topographical and biochemical
      cues using an assortment of nanoscale fabrication methods in order to elucidate
      which pattern dimensions are beneficial for controlling cell adhesion and
      differentiation.

PMID- 25383102
TI  - NEW PERSPECTIVES ON IMMIGRANT CONTEXTS OF RECEPTION: The cultural armature of
      cities.
AB  - We argue that important, overlooked differences in what we call the 'cultural
      armature' of Portland, Maine, and Danbury, Connecticut help explain the variation
      in how each city received new immigrants in recent years. Portland has a long
      history of contact with the outside world and used its cosmopolitan character to
      promote urban redevelopment and welcome immigrants from a range of countries of
      origin. Danbury's small-town, insular outlook, and the fact that most of its
      newcomers came from a single country of origin - some without legal documents -
      made immigrants' welcome more fragmented. While leaders in both cities speak of
      multiculturalism and tolerance, the 'cultural armature' of each led city leaders
      to put that talk into action differently. We describe how we see this 'cultural
      armature' at work and argue that it - in combination with demographic realities -
      led immigrants to be more warmly welcomed in Portland than in Danbury.

PMID- 25383103
TI  - Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic
      approach.
AB  - 5-Aminopyrazole-4-carbonitrile and ethyl 5-aminopyrazole-4-carboxylate, as
      potential trifunctional building blocks are introduced in a facile, chemo- and
      regioselective multicomponent assembly of imidazo[1,2-b]pyrazoles via the Groebke
      Blackburn-Bienayme reaction (GBB reaction). Besides the synthetic elaboration of
      a green-compatible isocyanide-based access in three-component mode, we describe
      an operationally simple, one-pot two-step GBB protocol for the rapid construction
      of a 46 membered imidazo[1,2-b]pyrazole library with yields up to 83%. 

PMID- 25383104
TI  - Multivalent glycosystems for nanoscience.

PMID- 25383106
TI  - Oligomerization of optically active N-(4-hydroxyphenyl)mandelamide in the
      presence of beta-cyclodextrin and the minor role of chirality.
AB  - The oxidative oligomerization of a chiral mandelamide derivative (N-(4
      hydroxyphenyl)mandelamide, 1) was performed in the presence of horseradish
      peroxidase, laccase and N,N'-bis(salicylidene)ethylenediamine-iron(II) to obtain
      chiral oligophenols 2. The low enantioselectivity of the enzymatic catalyzed
      asymmetric enantiomer-differentiating oligomerizations was investigated. In
      addition, the poor influence of cyclodextrin on the enantioselectivity of
      enzymatic catalyzed asymmetric enantiomer-differentiating oligomerizations was
      studied. 

PMID- 25383105
TI  - Autonomous assembly of synthetic oligonucleotides built from an expanded DNA
      alphabet. Total synthesis of a gene encoding kanamycin resistance.
AB  - BACKGROUND: Many synthetic biologists seek to increase the degree of autonomy in
      the assembly of long DNA (L-DNA) constructs from short synthetic DNA fragments,
      which are today quite inexpensive because of automated solid-phase synthesis.
      However, the low information density of DNA built from just four nucleotide
      "letters", the presence of strong (G:C) and weak (A:T) nucleobase pairs, the non
      canonical folded structures that compete with Watson-Crick pairing, and other
      features intrinsic to natural DNA, generally prevent the autonomous assembly of
      short single-stranded oligonucleotides greater than a dozen or so. RESULTS: We
      describe a new strategy to autonomously assemble L-DNA constructs from fragments
      of synthetic single-stranded DNA. This strategy uses an artificially expanded
      genetic information system (AEGIS) that adds nucleotides to the four (G, A, C,
      and T) found in standard DNA by shuffling hydrogen-bonding units on the
      nucleobases, all while retaining the overall Watson-Crick base-pairing geometry.
      The added information density allows larger numbers of synthetic fragments to
      self-assemble without off-target hybridization, hairpin formation, and non
      canonical folding interactions. The AEGIS pairs are then converted into standard
      pairs to produce a fully natural L-DNA product. Here, we report the autonomous
      assembly of a gene encoding kanamycin resistance using this strategy. Synthetic
      fragments were built from a six-letter alphabet having two AEGIS components, 5
      methyl-2'-deoxyisocytidine and 2'-deoxyisoguanosine (respectively S and B), at
      their overlapping ends. Gaps in the overlapped assembly were then filled in using
      DNA polymerases, and the nicks were sealed by ligase. The S:B pairs in the
      ligated construct were then converted to T:A pairs during PCR amplification. When
      cloned into a plasmid, the product was shown to make Escherichia coli resistant
      to kanamycin. A parallel study that attempted to assemble similarly sized genes
      with optimally designed standard nucleotides lacking AEGIS components gave
      successful assemblies of up to 16 fragments, but generally failed when larger
      autonomous assemblies were attempted. CONCLUSION: AEGIS nucleotides, by
      increasing the information density of DNA, allow larger numbers of DNA fragments
      to autonomously self-assemble into large DNA constructs. This technology can
      therefore increase the size of DNA constructs that might be used in synthetic
      biology.

PMID- 25383107
TI  - Synthesis and immunological evaluation of protein conjugates of Neisseria
      meningitidis X capsular polysaccharide fragments.
AB  - A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX)
      is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS)
      fragments conjugated to CRM197 as carrier protein have been confirmed at
      preclinical stage as promising candidates for vaccine development. However, more
      insights about the minimal epitope required for the immunological activity of
      MenX CPS are needed. We report herein the chemical conjugation of fully synthetic
      MenX CPS oligomers (monomer, dimer, and trimer) to CRM197. Moreover, improvements
      in some crucial steps leading to the synthesis of MenX CPS fragments are
      described. Following immunization with the obtained neoglycoconjugates, the
      conjugated trimer was demonstrated as the minimal fragment possessing immunogenic
      activity, even though significantly lower than a pentadecamer obtained from the
      native polymer and conjugated to the same protein. This finding suggests that
      oligomers longer than three repeating units are possibly needed to mimic the
      activity of the native polysaccharide. 

PMID- 25383108
TI  - New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones.
AB  - The one-pot three-component reactions of 1-substituted benzimidazoles with ethyl
      bromoacetate and electron-deficient alkynes, in 1,2-epoxybutane, gave a variety
      of pyrrolo[1,2-a]quinoxalin-4-ones and pyrrolo[1,2-a]benzimidazoles. The
      influence of experimental conditions on the course of reaction was investigated.
      A novel synthetic pathway starting from benzimidazoles unsubstituted at the five
      membered ring, alkyl bromoacetates and non-symmetrical electron-deficient alkynes
      in the molar ratio of 1:2:1, in 1,2-epoxybutane at reflux temperature, led
      directly to pyrrolo[1,2-a]quinoxalin-4-ones in fair yield by an one-pot three
      component reaction. 

PMID- 25383109
TI  - Phosphinocyclodextrins as confining units for catalytic metal centres.
      Applications to carbon-carbon bond forming reactions.
AB  - The capacity of two cavity-shaped ligands, HUGPHOS-1 and HUGPHOS-2, to generate
      exclusively singly phosphorus-ligated complexes, in which the cyclodextrin cavity
      tightly wraps around the metal centre, was explored with a number of late
      transition metal cations. Both cyclodextrin-derived ligands were assessed in
      palladium-catalysed Mizoroki-Heck coupling reactions between aryl bromides and
      styrene on one hand, and the rhodium-catalysed asymmetric hydroformylation of
      styrene on the other hand. The inability of both chiral ligands to form standard
      bis(phosphine) complexes under catalytic conditions was established by high
      pressure NMR studies and shown to have a deep impact on the two carbon-carbon
      bond forming reactions both in terms of activity and selectivity. For example,
      when used as ligands in the rhodium-catalysed hydroformylation of styrene, they
      lead to both high isoselectivity and high enantioselectivity. In the study
      dealing with the Mizoroki-Heck reactions, comparative tests were carried out with
      WIDEPHOS, a diphosphine analogue of HUGPHOS-2. 

PMID- 25383110
TI  - Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the
      evaluation of their cell compatibility.
AB  - This article reports the synthesis of a novel type of conjugate of three
      fundamental biological build blocks (i.e., saccharide, amino acids, and
      nucleobase) and their cell compatibility. The facile synthesis starts with the
      synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide
      synthesis (SPPS) to build the peptide segment (Phe-Arg-Gly-Asp or naphthAla-Phe
      Arg-Gly-Asp with fully protected groups), and later, an amidation reaction in
      liquid phase connects these three parts together. The overall yield of these
      multiple step synthesis is about 34%. Besides exhibiting excellent solubility,
      these conjugates of saccharide-amino acids-nucleobase (SAN), like the previously
      reported conjugates of nucleobase-amino acids-saccharide (NAS) and nucleobase
      saccharide-amino acids (NSA), are mammalian cell compatible. 

PMID- 25383111
TI  - A versatile delta-aminolevulinic acid (AlphaLA)-cyclodextrin bimodal conjugate
      prodrug for PDT applications with the help of intracellular chemistry.
AB  - Grafting of delta-aminolevulinic acid (1) moieties on the narrow periphery of a
      beta-cyclodextrin (beta-CD) derivative through hydrolysable bonds was
      implemented, in order to generate a water-soluble, molecular/drug carrier with
      the capacity to undergo intracellular transformation into protoporphyrin IX
      (PpIX), an endogenous powerful photosensitizer for photodynamic therapy (PDT).
      The water-soluble derivative 2 was prepared by esterifying delta-azidolevulinic
      acid with heptakis(6-hydroxyethylamino-6-deoxy)-beta-cyclodextrin, with an
      average degree of substitution, DS = 3. Delivery of water-soluble, colorless 2 to
      cells resulted in intense red fluorescence registered by confocal microscopy,
      evidently due to the engagement of the intracellular machinery towards formation
      of PpIX. Conjugate 2 was further complexed with a fluorescein-labeled model guest
      molecule which was successfully transported into the cells, thereby demonstrating
      the bimodal action of the derivative. The present work shows the versatility of
      CDs in smart applications and constitutes advancement to our previously shown
      PpIX-beta-CD conjugation both in terms of water solubility and lack of
      aggregation. 

PMID- 25383112
TI  - Total synthesis of the proposed structure of astakolactin.
AB  - The first total synthesis of the proposed structure of astakolactin, a
      sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris,
      has been achieved, mainly featuring Johnson-Claisen rearrangement, asymmetric
      Mukaiyama aldol reaction and MNBA-mediated lactonization. 

PMID- 25383113
TI  - Towards the sequence-specific multivalent molecular recognition of cyclodextrin
      oligomers.
AB  - Sequence-specific multivalent molecular recognition has been recognized to play a
      major role in biological processes. Furthermore, sequence-specific recognition
      motifs have been used in various artificial systems in the last years, e.g., to
      emulate biological processes or to build up new materials with highly specific
      recognition domains. In this article, we present the preparation of cyclodextrin
      (CD)-based strands and complementary and non-complementary strands modified with
      guest molecules and the investigation of their complexation behavior towards each
      other by isothermal titration calorimetry (ITC). As complementary binding motifs
      n-butyl and alpha-CD and adamantane and beta-CD were selected. It was found that
      it is possible to realize sequence-specific molecular recognition by the use of
      host-guest chemistry, but the recognition motifs as well as the linkages have to
      be chosen very carefully. In the case of trivalent systems one adamantane moiety
      must be included to induce preferred formation of 1:1 adducts. Due to the too
      weak interaction between n-butyl and alpha-CD these systems have a negative
      chelate cooperativity and open adducts are preferentially formed. As soon as two
      adamantane moieties are present, the complementary systems have a positive
      chelate cooperativity and double-stranded structures are favored over open
      adducts. In this system the n-butyl moiety provides insufficient discrimination
      towards alpha- and beta-CD and no sequence specificity is observed. By the
      combination of three adamantane moieties sequence specificity can be generated.
      Exclusively with the complementary CD sequence double-stranded structures are
      formed, with non-complementary strands aggregates of higher stoichiometry are
      generated. 

PMID- 25383114
TI  - A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline.
AB  - A convenient CuI/L-proline-catalyzed, two-step one-pot method has been developed
      for the preparation of indolo[1,2-a]quinazoline derivatives using a sequential
      Ullmann-type C-C and C-N coupling. This protocol provides an operationally simple
      and rapid strategy for preparing indolo[1,2-a]quinazoline derivatives and
      displays good functional group tolerance. All the starting materials are
      commercial available or can be easily prepared. 

PMID- 25383115
TI  - Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4
      naphthoquinone monoimines by air and light "on water".
AB  - A number of N-phenyl-1,4-naphthoquinone monoimines 6-10 were prepared by on-water
      oxidative phenylamination of 1,5-dihydroxynaphthalene (1) and 5-acetylamino-1
      hydroxynaphthalene (5) with oxygen-substituted phenylamines under aerobic
      conditions and either solar or green LED radiation, in the presence of rose
      bengal as singlet oxygen sensitizer. As compared to the conventional oxidative
      phenylamination procedures, this novel synthetic method offers the advantage of
      aerobic conditions "on water" instead of hazardous oxidant reagents currently
      employed in aqueous alcoholic media. 

PMID- 25383116
TI  - Synthesis of aromatic glycoconjugates. Building blocks for the construction of
      combinatorial glycopeptide libraries.
AB  - New aromatic glycoconjugate building blocks based on the trifunctional 3
      aminomethyl-5-aminobenzoic acid backbone and sugars linked to the backbone by a
      malonyl moiety were prepared via peptide coupling. The orthogonally protected
      glycoconjugates, bearing an acetyl-protected glycoside, were converted into their
      corresponding acids which are suitable building blocks for combinatorial
      glycopeptide synthesis. 

PMID- 25383117
TI  - Loose-fit polypseudorotaxanes constructed from gamma-CDs and PHEMA-PPG-PEG-PPG
      PHEMA.
AB  - A pentablock copolymer was prepared via the atom transfer radical polymerization
      of 2-hydroxyethyl methacrylate (HEMA) initiated by 2-bromoisobutyryl end-capped
      PPO-PEO-PPO as a macroinitiator in DMF. Attaching PHEMA blocks altered the self
      assembly process of the pentablock copolymer with gamma-CDs in aqueous solution.
      Before attaching the PHEMA, the macroinitiator was preferentially bent to pass
      through the inner cavity of gamma-CDs to give rise to tight-fit double-chain
      stranded polypseudorotaxanes (PPRs). After attaching the PHEMA, the resulting
      pentablock copolymer was single-chain stranded into the interior of gamma-CDs to
      form more stable, loose-fit PPRs. The results of (1)H NMR, WXRD, DSC, TGA, (13)C
      CP/MAS NMR and FTIR analyses indicated that gamma-CDs can accommodate and slip
      over PHEMA blocks to randomly distribute along the entire pentablock copolymer
      chain. This results in unique, single-chain stranded PPRs showing no
      characteristic channel-type crystal structure. 

PMID- 25383119
TI  - Host-guest-driven color change in water: influence of cyclodextrin on the
      structure of a copper complex of poly((4-hydroxy-3-(pyridin-3
      yldiazenyl)phenethyl)methacrylamide-co-dimethylacrylamide).
AB  - In the present work we report the synthesis of poly((4-hydroxy-3-(pyridin-3
      yldiazenyl)phenethyl)methacrylamide-co-dimethylacrylamide) and its reversible
      optical and complex-forming properties due to copper and cyclodextrin (CD)
      interactions. Color changing effects are characterized by UV-vis spectroscopy and
      the supramolecular behavior is investigated by dynamic light scattering
      experiments. 

PMID- 25383118
TI  - A small azide-modified thiazole-based reporter molecule for fluorescence and mass
      spectrometric detection.
AB  - Molecular probes are widely used tools in chemical biology that allow tracing of
      bioactive metabolites and selective labeling of proteins and other
      biomacromolecules. A common structural motif for such probes consists of a
      reporter that can be attached by copper(I)-catalyzed 1,2,3-triazole formation
      between terminal alkynes and azides to a reactive headgroup. Here we introduce
      the synthesis and application of the new thiazole-based, azide-tagged reporter 4
      (3-azidopropoxy)-5-(4-bromophenyl)-2-(pyridin-2-yl)thiazole for fluorescence, UV
      and mass spectrometry (MS) detection. This small fluorescent reporter bears a
      bromine functionalization facilitating the automated data mining of electrospray
      ionization MS runs by monitoring for its characteristic isotope signature. We
      demonstrate the universal utility of the reporter for the detection of an alkyne
      modified small molecule by LC-MS and for the visualization of a model protein by
      in-gel fluorescence. The novel probe advantageously compares with commercially
      available azide-modified fluorophores and a brominated one. The ease of
      synthesis, small size, stability, and the universal detection possibilities make
      it an ideal reporter for activity-based protein profiling and functional
      metabolic profiling. 

PMID- 25383120
TI  - Electrocarboxylation: towards sustainable and efficient synthesis of valuable
      carboxylic acids.
AB  - The near-unlimited availability of CO2 has stimulated a growing research effort
      in creating value-added products from this greenhouse gas. This paper presents
      the trends on the most important methods used in the electrochemical synthesis of
      carboxylic acids from carbon dioxide. An overview is given of different substrate
      groups which form carboxylic acids upon CO2 fixation, including mechanistic
      considerations. While most work focuses on the electrocarboxylation of substrates
      with sacrificial anodes, this review considers the possibilities and challenges
      of implementing other synthetic methodologies. In view of potential industrial
      application, the choice of reactor setup, electrode type and reaction pathway has
      a large influence on the sustainability and efficiency of the process. 

PMID- 25383123
TI  - Microsolvation and sp(2)-stereoinversion of monomeric alpha-(2,6-di-tert
      butylphenyl)vinyllithium as measured by NMR.
AB  - The beta-unsubstituted title compound dissolves in THF as a uniformly trisolvated
      monomer, whereas it forms exclusively disolvated monomers in tert-butyl methyl
      ether, Et2O, TMEDA, or toluene with TMEDA (1.4 equiv). This was established at
      low temperatures through the observation of separated NMR signals for free and
      lithium-coordinated ligands and/or through the patterns and magnitudes of
      (13)C,(6)Li NMR coupling constants. An aggregated form was observed only with
      Et2O (2 equiv) in toluene as the solvent. The olefinic geminal interproton
      coupling constants of the H2C= part can be used as a secondary criterion to
      differentiate between these differently solvated ground-states (3, 2, or <2
      coordinated ligands per Li). Due to a kinetic trisolvation privilege of THF, the
      cis/trans sp(2)-stereoinversion rates could be measured through analyses of (1)H
      NMR line broadening and coalescence only in THF as the solvent: The
      pseudomonomolecular (because THF-catalyzed), ionic mechanism is initialized by a
      C-Li bond heterolysis with the transient immobilization of one additional THF
      ligand, followed by stereoinversion of the quasi-sp(2)-hybridized carbanionic
      center in cooperation with a "conducted tour" migration of Li(+)(THF)4 along the
      alpha-aryl group within the solvent-separated ion pair. 

PMID- 25383121
TI  - Formal total syntheses of classic natural product target molecules via palladium
      catalyzed enantioselective alkylation.
AB  - Pd-catalyzed enantioselective alkylation in conjunction with further synthetic
      elaboration enables the formal total syntheses of a number of "classic" natural
      product target molecules. This publication highlights recent methods for setting
      quaternary and tetrasubstituted tertiary carbon stereocenters to address the
      synthetic hurdles encountered over many decades across multiple compound classes
      spanning carbohydrate derivatives, terpenes, and alkaloids. These
      enantioselective methods will impact both academic and industrial settings, where
      the synthesis of stereogenic quaternary carbons is a continuing challenge. 

PMID- 25383122
TI  - Regio- and stereoselective synthesis of new diaminocyclopentanols.
AB  - The optimal conditions for regio- and stereoselective epoxide ring opening of N,N
      disubstituted 1,2-epoxy-3-aminocyclopentanes by different nucleophilic reagents
      have been developed. The substituents on the nitrogen atom in the epoxide
      precursor and the orientation of the oxirane ring are crucial for the reaction
      outcome. Thus, treatment of (1RS,2SR,3SR)-1,2-epoxy-3-(N,N
      dibenzylamino)cyclopentane (3b) with amines gave a mixture of C1 and C2
      regioadducts, while the use of (1RS,2SR,3SR)-1,2-epoxy-3-(N-benzyl-N
      methylamino)cyclopentane (3a) led ultimately to C1 adducts. Base-catalyzed
      aminolysis of epoxides 6a,b afforded mainly C1 adducts 13a,b arising from trans
      diaxal opening of the epoxide ring. Using a Lewis acid catalyst, epoxides 6a,b
      were transformed into diaminocyclopentanols 14a,b via an alternative pathway
      involving the formation of aziridinium intermediate 17. 

PMID- 25383124
TI  - Superoxide chemistry revisited: synthesis of tetrachloro-substituted
      methylenenortricyclenes.
AB  - An unexpected reactivity of the superoxide ion leading to the synthesis of
      tetrachloroaryl/vinyl-substituted nortricyclenes through its dual mode of action
      has been reported. KO2 was found to be superior and the only reagent to perform
      this kind of reaction over other conventional bases. Addition of the antioxidant
      BHT (2,6-di-tert-butyl-4-methylphenol) improved the yields of
      methylenenortricyclenes. A complete deuterium incorporation was observed in the
      superoxide-mediated reaction in DMSO-d 6. Friedel-Crafts acylation reactions of 3
      methylenenorticyclenes yielded 2-propanone-substituted pentachloronorbornenes. 

PMID- 25383125
TI  - Synthesis and biological evaluation of novel N-alpha-haloacylated homoserine
      lactones as quorum sensing modulators.
AB  - Novel N-alpha-haloacylated homoserine lactones, in which a halogen atom was
      introduced at the alpha-position of the carbonyl function of the N-acyl chain,
      have been studied as quorum sensing (QS) modulators and compared with a library
      of natural N-acylated homoserine lactones (AHLs). The series of novel analogues
      consists of alpha-chloro, alpha-bromo and alpha-iodo AHL analogues. Furthermore,
      the biological QS activity of the synthetic AHL analogues compared to the natural
      AHLs was evaluated. Halogenated analogues demonstrated a reduced activity in the
      Escherichia coli JB523 bioassay, with the alpha-iodo lactones being the less
      active ones and the alpha-chloro AHLs the most potent QS agonists. Most of the
      alpha-haloacylated analogues did not exhibit a significant reduction when tested
      in the QS inhibition test. Therefore, these novel analogues could be utilized as
      chemical probes for QS structure-activity studies. 

PMID- 25383126
TI  - Selenium halide-induced bridge formation in [2.2]paracyclophanes.
AB  - An addition/elimination sequence of selenium halides to pseudo-geminally
      bis(acetylene) substituted [2.2]paracyclophanes leads to new bridges with an endo
      exo-diene substructure. The reactions have been found to be sensitive to the
      substitution of the ethynyl group. The formation of dienes with a zig-zag
      configuration is related to that observed for non-conjugated cyclic diynes of
      medium ring size. 

PMID- 25383127
TI  - An integrated photocatalytic/enzymatic system for the reduction of CO2 to
      methanol in bioglycerol-water.
AB  - A hybrid enzymatic/photocatalytic approach for the conversion of CO2 into
      methanol is described. For the approach discussed here, the production of one mol
      of CH3OH from CO2 requires three enzymes and the consumption of three mol of
      NADH. Regeneration of the cofactor NADH from NAD(+) was achieved by using visible
      light-active, heterogeneous, TiO2-based photocatalysts. The efficiency of the
      regeneration process is enhanced by using a Rh(III)-complex for facilitating the
      electron and hydride transfer from the H-donor (water or a water-glycerol
      solution) to NAD(+). This resulted in the production of 100 to 1000 mol of CH3OH
      from one mol of NADH, providing the possibility for practical application. 

PMID- 25383128
TI  - Versatile synthesis of amino acid functionalized nucleosides via a domino
      carboxamidation reaction.
AB  - Functionalized oligonucleotides have recently gained increased attention for
      incorporation in modified nucleic acid structures both for the design of aptamers
      with enhanced binding properties as well as the construction of catalytic DNA and
      RNA. As a shortcut alternative to the incorporation of multiple modified
      residues, each bearing one extra functional group, we present here a
      straightforward method for direct linking of functionalized amino acids to the
      nucleoside base, thus equipping the nucleoside with two extra functionalities at
      once. As a proof of principle, we have introduced three amino acids with
      functional groups frequently used as key-intermediates in DNA- and RNAzymes via
      an efficient and straightforward domino carboxamidation reaction. 

PMID- 25383129
TI  - Synthesis of graft polyrotaxane by simultaneous capping of backbone and grafting
      from rings of pseudo-polyrotaxane.
AB  - Graft polyrotaxanes, with poly(epsilon-caprolactone) (PCL) graft chains on the
      ring components were synthesized by the simultaneous ring-opening polymerization
      of epsilon-caprolactone from both ends of the backbone polymer, an end
      functionalized polyethylene glycol (PEG) and the formation of inclusion complexes
      with alpha-cyclodextrin (alpha-CD). PEG with multiple functional groups at each
      end was prepared by the condensation of PEG-amine and D-gluconic acid; the PEG
      derivative formed an inclusion complex with alpha-CD. The polymerization of
      multiple hydroxy groups at the backbone ends resulted in a star-shaped end group,
      which served as a bulky capping group to prevent dethreading. In contrast, PEG
      with only one hydroxy group at each end did not produce polyrotaxanes, indicating
      that single PCL chains were too thin to confine alpha-CDs to the complex. In
      addition, the grafting polymerization proceeded properly only when robust
      hydrogen bonds formed between alpha-CDs were dissociated using a basic catalyst.
      Since the dissociation also induced dethreading, kinetic control of the
      polymerization and dissociation were crucial for producing graft polyrotaxanes.
      Consequently, this three-step reaction yielded graft polyrotaxanes in a good
      yield, demonstrating a significant simplification of the synthesis of graft
      polyrotaxanes. 

PMID- 25383130
TI  - Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate.
AB  - An analogue of thiamine having a furan ring in place of the thiazolium ring has
      been synthesised by a short and efficient route, involving gold(I)-catalysed
      cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of
      thiamine diphosphate (ThDP) was also made and tested for binding to and
      inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis (overexpressed
      in E. coli with a N-terminal His-tag). It is a very strong inhibitor, with a K i
      value of 32.5 pM. It was also shown that the furan analogue of thiamine can be
      functionalised at the C-2 position, which will allow access to mimics of reaction
      intermediates of various ThDP-dependent enzymes. 

PMID- 25383132
TI  - HYPOTHESIS SETTING AND ORDER STATISTIC FOR ROBUST GENOMIC META-ANALYSIS.
AB  - Meta-analysis techniques have been widely developed and applied in genomic
      applications, especially for combining multiple transcriptomic studies. In this
      paper, we propose an order statistic of p-values (rth ordered p-value, rOP)
      across combined studies as the test statistic. We illustrate different hypothesis
      settings that detect gene markers differentially expressed (DE) "in all studies",
      "in the majority of studies", or "in one or more studies", and specify rOP as a
      suitable method for detecting DE genes "in the majority of studies". We develop
      methods to estimate the parameter r in rOP for real applications. Statistical
      properties such as its asymptotic behavior and a one-sided testing correction for
      detecting markers of concordant expression changes are explored. Power
      calculation and simulation show better performance of rOP compared to classical
      Fisher's method, Stouffer's method, minimum p-value method and maximum p-value
      method under the focused hypothesis setting. Theoretically, rOP is found
      connected to the naive vote counting method and can be viewed as a generalized
      form of vote counting with better statistical properties. The method is applied
      to three microarray meta-analysis examples including major depressive disorder,
      brain cancer and diabetes. The results demonstrate rOP as a more generalizable,
      robust and sensitive statistical framework to detect disease-related markers.

PMID- 25383131
TI  - Volatile phytochemicals as mosquito semiochemicals.
AB  - Plant biochemical processes result in the release of an array of volatile
      chemical substances into the environment, some of which are known to play
      important plant fitness enhancing functions, such as attracting pollinators,
      thermal tolerance of photosynthesis, and defense against herbivores. Cunningly,
      phytophagous insects have evolved mechanisms to utilize these volatiles to their
      own advantage, either to colonize a suitable host for feeding, reproduction and
      oviposition or avoid an unsuitable one. The volatile compounds involved in plant
      insect chemical interactions have been widely exploited in the management of
      agricultural pests. On the other hand, use of plant volatiles in the management
      of medically important insects is limited, mainly due to paucity of information
      on their role in disease vector-plant interactions. To date, a total of 29 plant
      volatile compounds from various chemical classes, including phenols, aldehydes,
      alcohols, ketones and terpenes, have been identified as mosquito semiochemicals.
      In this review, we present highlights of mosquito-plant interactions, the
      available evidence of nectar feeding, with particular emphasis on sources of
      plant attractants, methods of plant volatile collection and the candidate plant
      volatile compounds that attract mosquitoes to nectar sources. We also highlight
      the potential application of these phytochemical attractants in integrated
      mosquito management.

PMID- 25383133
TI  - Engineering a Robust Photovoltaic Device with Quantum Dots and Bacteriorhodopsin.
AB  - We present a route toward a radical improvement in solar cell efficiency using
      resonant energy transfer and sensitization of semiconductor metal oxides with a
      light-harvesting quantum dot (QD)/bacteriorhodopsin (bR) layer designed by
      protein engineering. The specific aims of our approach are (1) controlled
      engineering of highly ordered bR/QD complexes; (2) replacement of the liquid
      electrolyte by a thin layer of gold; (3) highly oriented deposition of bR/QD
      complexes on a gold layer; and (4) use of the Forster resonance energy transfer
      coupling between bR and QDs to achieve an efficient absorbing layer for dye
      sensitized solar cells. This proposed approach is based on the unique optical
      characteristics of QDs, on the photovoltaic properties of bR, and on state-of-the
      art nanobioengineering technologies. It permits spatial and optical coupling
      together with control of hybrid material components on the bionanoscale. This
      method paves the way to the development of the solid-state photovoltaic device
      with the efficiency increased to practical levels.

PMID- 25383134
TI  - Mechanisms of alcohol-induced hepatocellular carcinoma.
AB  - Chronic alcohol abuse is a major risk factor for hepatocellular carcinoma (HCC),
      the third leading cause of cancer deaths worldwide. Alcohol can also function
      synergistically with other risk factors to cause HCC. Hence, alcohol consumption
      is a major factor affecting hepatic carcinogenesis in millions and the cause of a
      substantial public health burden. Chronic alcohol consumption interferes with
      several host anti-tumor mechanisms, thereby facilitating hepatocyte proliferation
      and tumorigenesis. This review summarizes the major mechanisms of alcohol-induced
      HCC. These include pathways of ethanol metabolism, alcohol-induced oxidative
      stress and hypomethylation of DNA, and interplay of alcohol with iron elevation,
      retinoid metabolism, the immune system, inflammatory pathways, and
      neoangiogenesis. The relevance of each pathway in affecting HCC transformation is
      a topic of intense investigation. Ongoing research will enhance our insight into
      the alcohol-induced occurrence of HCC and offer hope in developing better
      therapeutics. 

PMID- 25383136
TI  - Peer mentorship teaches social tools for pain self-management: A case study.
AB  - : Pain in children can become chronic and disabling, associated with high degrees
      of social isolation from schooling absences, physical limitations that prevent
      participation in social settings, and difficulties forming self-identity. This
      lack of social support network impairs social coping skills and can lead to
      worsening pain symptoms. OBJECTIVE: In this case study, we describe a new program
      to disrupt the cycle of social isolation and chronic pain by emphasizing social
      coping skills via peer mentorship. The program aimed to utilize peers who have
      learned to self-manage their own chronic pain to assist patients with social
      coping skills to reduce isolation caused by chronic pain conditions. STUDY GROUP:
      Children and adolescents with chronic pain. METHODS: This case describes the
      experience of a 17 year-old, African American boy with diffuse chronic body pain
      as a participant ("the mentee") in the program; his mentor was a 19 year-old girl
      with chronic pain associated with rheumatoid arthritis. The mentor received six
      hours of training and she mentored the patient in 10 weekly sessions. RESULTS:
      The mentee connected very well with his mentor through sharing similar pain
      experiences. He demonstrated improvements in positive affect, sleep, social
      coping, and perception of bodily pain on a variety of quantitative measures.
      Qualitative data from interviews also suggested that the mentee learned important
      social coping skills through peer mentorship. CONCLUSIONS: A peer mentoring
      approach to chronic pain may help alleviate social isolation in adolescents and
      result in improvements in a number of associated symptoms.

PMID- 25383135
TI  - Chronic urticaria: new management options.
AB  - Chronic urticaria is defined as episodic or daily hives lasting for at least 6
      weeks and impairs quality of life. Two main subtypes include chronic idiopathic
      (spontaneous) urticaria and inducible (physical) urticaria, but some patients
      have urticarial vasculitis. "Autoimmune chronic urticaria" implies the presence
      of histamine releasing or mast cell activating autoantibodies to IgE or
      FcepsilonRI, the high affinity receptor on mast cells and basophils. In patients
      not readily controlled with labeled dosages of second generation H1 receptor
      antagonists (antihistamines), there is evidence for reduction of urticaria using
      up to 4 fold increases in labeled dosages. The biologic modifier, omalizumab,
      helps to reduce lesions of chronic urticaria within 1-2 weeks. 

PMID- 25383137
TI  - Leveraging Online Learning Resources to Teach Core Research Skills to
      Undergraduates at a Diverse Research University.
AB  - Today's students have unique learning needs and lack knowledge of core research
      skills. In this program report, we describe an online approach that we developed
      to teach core research skills to freshman and sophomore undergraduates.
      Specifically, we used two undergraduate kinesiology (KIN) courses designed to
      target students throughout campus (KIN1304: Public Health Issues in Physical
      Activity and Obesity) and specifically kinesiology majors (KIN1252: Foundations
      of Kinesiology). Our program was developed and validated at the 2nd largest
      ethnically diverse research university in the United States, thus we believe that
      it would be effective in a variety of student populations.

PMID- 25383138
TI  - Structure, Movement, Sound, and Perception.
AB  - Models that take the form of artificial talkers and speech synthesis systems have
      long been used as a means of understanding both speech production and speech
      perception. The article begins with a brief history of two artificial speaking
      devices that exemplify the representation of speech production as a system of
      modulations. The development of a recent airway modulation model is then
      described that simulates the time-varying changes of the vocal tract and acoustic
      wave propagation. The result is a type of artificial talker that can be used to
      study various aspects of how sound is generated by humans and how that sound is
      perceived by a listener.

PMID- 25383139
TI  - The role of oxidative stress and the effects of antioxidants on the incidence of
      infectious complications of chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by a predominant humoral
      immune deficiency predisposing the patients to infections. Oxidative stress leads
      to an increased immunoglobulin k light chain production in B cells and
      contributes to the antibodies' deficiency and hypogammaglobulinemia. Aim of the
      Study. To evaluate the global oxidative status in patients with CLL and to
      determine whether the administration of antioxidants decreases complications due
      to infections. Patients and Method. We studied 84 patients with CLL stratified by
      Binet staging. Free oxygen radicals and antioxidant status were determined by the
      FORT and FORD test, respectively, at diagnosis and in the presence of infections.
      The patients were distributed in two groups: group A, treated only with
      antileukemic treatment, and group B, treated with antileukemic treatment and
      antioxidants. Results. By FORD and FORT assay, all patients had at diagnosis a
      low antioxidant capacity, and high levels of hydroperoxides. Infectious
      complications were more frequent in group A (B/C stages of disease) than in group
      B. Administrations of antioxidants stimulated the immune response and decreased
      infectious complications in CLL. Conclusions. Administrations of antioxidants and
      a healthy life style may improve the quality of life of patients with CLL and
      reduce the risk of infectious complications. 

PMID- 25383140
TI  - PRAK interacts with DJ-1 and prevents oxidative stress-induced cell death.
AB  - As a core member of p38 MAPK signal transduction pathway, p38 regulated/activated
      kinase (PRAK) is activated by cellular stresses. However, the function of PRAK
      and its downstream interacting partner remain undefined. Using a yeast two-hybrid
      system, we identified DJ-1 as a potential PRAK interacting protein. We further
      verified that DJ-1 bound to PRAK in vitro and in vivo and colocalized with PRAK
      in the nuclei of NIH3T3 cells. Furthermore, following H2O2 stimulation the
      majority of endogenous DJ-1 in PRAK(+/+) cells still remained in the nucleus,
      whereas most DJ-1 in PRAK(-/-) cells translocated from the nucleus into the
      cytoplasm, indicating that PRAK is essential for DJ-1 to localize in the nucleus.
      In addition, PRAK-associated phosphorylation of DJ-1 was observed in vitro and in
      vivo of H2O2-challenged PRAK(+/+) cells. Cytoplasmic translocation of DJ-1 in
      H2O2-treated PRAK(-/-) cells lost its ability to sequester Daxx, a death protein,
      in the nucleus, and as a result, Daxx gained access to the cytoplasm and
      triggered cell death. These data highlight that DJ-1 is the downstream
      interacting target for PRAK, and in response to oxidative stress PRAK may exert a
      cytoprotective effect by facilitating DJ-1 to sequester Daxx in the nucleus, thus
      preventing cell death.

PMID- 25383142
TI  - Benefiting from AIDS in Contemporary Nigeria.

PMID- 25383143
TI  - Breakthrough in Photonics 2013: Photoacoustic Tomography in Biomedicine.
AB  - Photoacoustic tomography (PAT) is one of the fastest growing biomedical imaging
      modalities in the last decade. Building on its high scalability and complementary
      imaging contrast to other mainstream modalities, PAT has gained substantial
      momentum in both preclinical and clinical studies. In 2013, PAT has grown
      markedly in both its technological capabilities and biomedical applications. In
      particular, breakthroughs have been made in super-resolution imaging, deep blood
      flow measurement, small animal resting state brain mapping, video rate functional
      human imaging, and human breast imaging. These breakthroughs have either
      successfully solved long-standing technical issues in PAT or significantly
      enhanced its imaging capability. This Review will summarize state-of-the-art
      developments in PAT and highlight a few representative achievements of the year
      2013.

PMID- 25383141
TI  - Electrochemically reduced water protects neural cells from oxidative damage.
AB  - Aging-related neurodegenerative disorders are closely associated with
      mitochondrial dysfunction and oxidative stresses and their incidence tends to
      increase with aging. Brain is the most vulnerable to reactive species generated
      by a higher rate of oxygen consumption and glucose utilization compared to other
      organs. Electrochemically reduced water (ERW) was demonstrated to scavenge
      reactive oxygen species (ROS) in several cell types. In the present study, the
      protective effect of ERW against hydrogen peroxide (H2O2) and nitric oxide (NO)
      was investigated in several rodent neuronal cell lines and primary cells. ERW was
      found to significantly suppress H2O2 (50-200 MUM) induced PC12 and SFME cell
      deaths. ERW scavenged intracellular ROS and exhibited a protective effect against
      neuronal network damage caused by 200 MUM H2O2 in N1E-115 cells. ERW
      significantly suppressed NO-induced cytotoxicity in PC12 cells despite the fact
      that it did not have the ability to scavenge intracellular NO. ERW significantly
      suppressed both glutamate induced Ca(2+) influx and the resulting cytotoxicity in
      primary cells. These results collectively demonstrated for the first time that
      ERW protects several types of neuronal cells by scavenging ROS because of the
      presence of hydrogen and platinum nanoparticles dissolved in ERW.

PMID- 25383144
TI  - Demineralized bone matrix for alveolar cleft management.
AB  - The aim of this article is to describe the results of the use of demineralized
      bone matrix putty in alveolar cleft of patients with cleft lip and palate. We
      performed a prospective, descriptive case series study, in which we evaluated the
      results of the management of alveolar clefts with demineralized bone matrix.
      Surgery was performed in 10 patients aged between 7 and 26 years (mean 13 years),
      involving a total of 13 clefts in the 10 patients. A preoperative cone beam
      computed tomography (CBCT) was taken to the patients in whom the width of the
      cleft was measured from each edge of the cleft reporting values between 5.76 and
      16.93 mm (average, 11.18 mm). The densities of the clefts were measured with a
      CBCT, 6 months postoperative to assess bone formation. The results showed a
      register of gray values of 1,148 to 1,396 (mean, 1,270). The follow-up was
      conducted for 15 to 33 months (mean, 28.2 months). The results did not show
      satisfactory bone formation in the cleft of patients with the use of
      demineralized bone matrix. 

PMID- 25383145
TI  - Thermoplastic vestibuloplasty: a novel technique for treatment of lip and cheek
      adhesion.
AB  - Lip and cheek adhesion to the opposing alveolus with complete or partial loss of
      the vestibular dimension represents a challenging problem for reconstruction. It
      usually occurs due to primary inadequate vestibular soft tissue repair following
      complicated trauma cases, burns, and lesions of the oral cavity. Surgical removal
      of scar tissue and creation of new vestibule is complicated by readhesion between
      the opposing connective tissue surfaces. Skin grafts and acellular dermal matrix
      represent the most dominant modalities used to treat deficient vestibule
      dimensions, but they are difficult to fix and lack the required stability during
      healing. Several devices have been created in an attempt to keep the tissues
      apart but their complex anchorage methods seriously reduced their reliability and
      usage. We devised a simple and reliable technique "thermoplastic vestibuloplasty"
      (TV) that benefit from the inherent reepithelialization capabilities of the oral
      mucosa to prevent readhesion and to resurface the created vestibule with its
      exact tissue color and texture. In total, 10 patients suffering from complete or
      partial lip or cheek adhesion with concomitant loss of vestibule were surgically
      treated by excising scar tissue and creating a new vestibule, followed by TV
      technique. Pre and posttreatment results were compared in terms of vestibular
      length, lip or cheek mobility, and change by time in vestibular length from 2
      weeks up to 3 months. Moreover, the patient satisfaction and outcomes were
      measured using visual analogue scale score. All patients tolerated the procedure
      without complication. The mean vestibule length and mobility significantly
      increased from 3.8 + 0.6 mm to 11.4 + 1.4 mm (p < 0.001) and from 0.3 to 2 (p <
      0.001), respectively. Regarding the stability of the achieved vestibular length
      it decreased by 14% when compared from 2 weeks to 3 months postoperatively. TV
      technique is a new simple and reliable technique that can effectively prevent
      readhesion of opposing connective tissue surfaces until intrinsic
      reepithelialization can resurface the newly created vestibular tissues forming a
      stable vestibular length with excellent color and texture. 

PMID- 25383146
TI  - Frontal sinus obliteration with iliac crest bone grafts. Review of 8 cases.
AB  - This study evaluated postoperative results of 8 cases of frontal sinus fractures
      treated by frontal sinus obliteration with autogenous bone from the anterior
      iliac crest. PATIENTS AND METHODS: The medical charts of patients sequentially
      treated for frontal sinus fractures by obliteration with autogenous cancellous
      iliac crest bone in the Oral and Maxillofacial Surgery Division of this
      institution were reviewed. From those, eight had complete records and adequately
      described long-term follow-up. All were operated by the same surgical team. Those
      patients were recalled and independently evaluated by 2 examiners. Radiographs
      and/or CT scans were available for this evaluation. Associated fractures and
      complications were noted. The average postoperative follow-up was 7 years,
      ranging from 3 to 16 years. The main complication was infection. Four patients
      (50%) had uneventful long-term follow-ups and four (50%) experienced
      complications requiring reoperation. Based on the studied sample studied the
      authors conclude that the obliteration with autogenous bone presented a high
      percentage of complications in this series.

PMID- 25383147
TI  - Inferior alveolar nerve injuries associated with mandibular fractures at risk: a
      two-center retrospective study.
AB  - The aim of the study was to investigate the incidence of the inferior alveolar
      nerve (IAN) injury in mandibular fractures. This study is based on two databases
      that have continuously recorded patients hospitalized with maxillofacial
      fractures in two departments-Department of Maxillofacial Surgery, Vrije
      Universiteit University Medical Center, Amsterdam, the Netherlands, and Division
      of Maxillofacial Surgery, San Giovanni Battista Hospital, Turin, Italy.
      Demographic, anatomic, and etiology variables were considered for each patient
      and statistically assessed in relation to the neurosensory IAN impairment.
      Statistically significant associations were found between IAN injury and fracture
      displacement (p = 0.03), isolated mandibular fractures (p = 0.01), and angle
      fractures (p = 0.004). A statistically significant association was also found
      between IAN injury and assaults (p = 0.03). Displaced isolated mandibular angle
      fractures could be considered at risk for increased incidence of IAN injury.
      Assaults seem to be the most important etiological factor that is responsible for
      IAN lesions. 

PMID- 25383149
TI  - Subcutaneous Emphysema following Emergent Surgical Conventional Tracheostomy.
AB  - In maxillofacial surgery, tracheostomy is indicated in congenital, inflammatory,
      oncologic, or traumatic respiratory obstruction. In traumatic cases, however, it
      is sometimes hard to implement. We describe subcutaneous emphysema following
      emergent surgical conventional tracheostomy performed after stab injury to the
      floor of the mouth. We analyze the course that led to this complication and
      discuss suggestions on how to avoid it. In addition, we review the literature to
      improve our knowledge and practice regarding this entity. Massive subcutaneous
      neck emphysema occurred because ventilation started at the time when the
      hemorrhage was not completely managed and the tracheal tube was not fully
      secured. In traumatic cases with profound bleeding, hemorrhage management must be
      performed carefully. The recommendation not to ventilate until the hemorrhage is
      completely managed should be observed. 

PMID- 25383148
TI  - Analysis of Road Traffic Crashes-Related Maxillofacial Injuries Severity and
      Concomitant Injuries in 201 Patients Seen at the UCH, Ibadan.
AB  - The objective of this study was to determine the prevalence of road traffic
      crashes (RTC)-related maxillofacial injuries, the concomitant injuries occurring
      with them, and to assess the relationship between the severity of maxillofacial
      and concomitant injuries. This was a prospective study involving 201 victims of
      RTC seen at the Accident and Emergency Department of the University College
      Hospital, Ibadan with maxillofacial injuries during the study period. Demographic
      data of the patients, the types of maxillofacial injuries, and concomitant
      injuries sustained were recorded. Severity of maxillofacial injury was determined
      using the maxillofacial injury severity scale (MFISS), while the severity of
      concomitant injuries was based on the ISS. Correlations between types and
      severity of maxillofacial injury and types and severity of concomitant injury
      were conducted to determine the predictability of concomitant injuries based on
      maxillofacial injury severity. Data were processed using SPSS Statistical
      software (SPSS, version 20.0 for windows, IBM SPSS Inc, Chicago, IL).
      Maxillofacial injuries constituted 25.4% of RTC-related admission by the Accident
      and Emergency Department. A total of 151 (75.1%) patients who presented with
      concomitant injuries participated in the study. Eighty-one (53.6%) sustained
      injuries to more than one body region. Head injury was the commonest (99, 65.6%)
      concomitant injury, followed by orthopedic injury (69, 45.7%). Increasing
      severity of maxillofacial injury showed a positive correlation with increasing
      ISS. Also, positive correlation was noted with increasing severity of
      maxillofacial injury and presence of polytrauma (p = 0.01), traumatic brain
      injury (p = 0.034), and eye injuries (p = 0.034). There was a high prevalence of
      maxillofacial injuries in victims of RTC. There was a high incidence of
      concomitant injuries noted with these maxillofacial injuries. Significantly, this
      study showed a direct relationship between the severity of maxillofacial injury
      and head, ocular and polytrauma. This study further emphasizes the need for
      thorough examination of patients presenting with RTC-related maxillofacial
      injuries. 

PMID- 25383150
TI  - Natural course of orbital roof fractures.
AB  - The natural course of several isolated and nonisolated orbital roof fractures is
      reported, by showing four cases in which a "wait and see" policy was followed.
      All four cases showed spontaneous repositioning and stabilizing of the fracture
      within less than a year. This might be explained by the equilibrium between the
      intraorbital and intracranial pressures. 

PMID- 25383151
TI  - Use of intraoperative computed tomography in complex craniofacial trauma: an
      example of on-table change in management.
AB  - The primary goals in repairing complex craniofacial fractures are restoration of
      occlusion and mastication, and anatomic reconstruction of a symmetric facial
      skeleton. Failure to accomplish these goals may result in the need for secondary
      operations. Recognition of malreduction may not be appreciated until review of a
      postoperative computed tomographic (CT) scan. Intraoperative CT scanning enables
      immediate on-table assessment of reduction and fixation, allowing alteration of
      the surgical plan as needed. We report using intraoperative CT scanning while
      repairing a panfacial injury in which malreduction was appreciated
      intraoperatively and corrected. Intraoperative CT can be used to improve outcomes
      and quality of complex facial fracture repair. 

PMID- 25383152
TI  - Fracture of the vomero-premaxillary junction in a repaired bilateral cleft lip
      and palate patient.
AB  - Although dental trauma is common in bilateral cleft lip and palate (BCLP),
      patients' reports on bony fractures of the vomero-premaxillary junction cannot be
      found. The aim of this report is to illustrate clinical findings and the
      technique of fracture fixation in a child suffering from a fractured vomero
      premaxillary junction as well as subsequent columella lengthening. A 4-year-old
      girl with a repaired BCLP presented with an open mucosal laceration and fractured
      vomero-premaxillary junction. Open reduction and fixation of the dislocated
      premaxilla was performed under general anesthesia. Fractured bone pieces of the
      vomero-premaxillary junction were removed and sharp bone edges at the vomer and
      the premaxilla were grinded. The repositioned premaxilla was fixed to the lateral
      alveolar arches with two mucoperiosteal sutures on each side. Additional
      columella lengthening was performed 2 years later. All family members were very
      happy about the new aesthetics of the girl. Although rare, fractures of the
      vomero-premaxillary junction present several challenges to clinicians related to
      anatomical, physiological, and psychological issues. Immediate and minimal
      invasive treatment strategies are recommended when managing such cases. 

PMID- 25383153
TI  - Osteochondroma of coronoid process: a rare etiology of jacob disease.
AB  - Jacob disease is a rare entity consisting of the formation of a pseudojoint
      between the inner surface of the zygoma and the coronoid process. This requires
      constant contact between the two implicated surfaces. It can be achieved by two
      mechanisms: one by an enlarged coronoid process and two by an anterior
      displacement of the coronoid process caused by a temporomandibular joint (TMJ)
      disorder. Although von Langenbeck described coronoid process hyperplasia in 1853,
      Oscar Jacob was the first author to describe the pathology in 1899. Since then,
      only a few cases have been published in the literature. The authors report a rare
      case of Jacob disease caused by an osteochondroma of the coronoid process, which
      is even less common, and review the literature. 

PMID- 25383154
TI  - An unusual transorbital penetrating injury and principles of management.
AB  - The objective of this study was to present an unusual low velocity transorbital
      penetrating injury. The study design was a clinical record (case report). A 38
      year-old gentleman tripped and fell face first onto the wing of an ornamental
      brass eagle. This penetrated the inferomedial aspect of the right orbit,
      breaching the lamina papyracea to extend into the ethmoid sinuses and reaching
      the dura of the anterior cranial fossa. The foreign body was removed in theater
      under a joint ophthalmology and ENT procedure. The patient was left with reduced
      visual acuity in the right eye but no other long-term sequelae. Transorbital
      penetrating injury presents unusual challenges to investigation and management
      requiring a multidisciplinary approach to prevent significant morbidity and
      mortality. If managed well the prognosis is good. 

PMID- 25383155
TI  - Bilateral, Bipedicled DIEP Flap for Staged Reconstruction of Cranial Deformity.
AB  - The deep inferior epigastric perforator (DIEP) adipocutaneous flap is a versatile
      flap that has been most popularly used in breast reconstruction. However, it has
      been applied to many other anatomic areas and circumstances that require free
      tissue transfer. We present a case report of the use of the DIEP flap for the
      reconstruction of severe craniomaxillofacial deformity complicated by indolent
      infection in a gentleman with infected hardware and methyl methacrylate overlay
      used in previous repair of traumatic injuries suffered from a motor vehicle
      collision. The reconstruction was done in a staged, two-step fashion that allowed
      for adequate infection eradication and treatment using a bilateral, bipedicled
      DIEP flap for tissue coverage and intravenous antibiotics before the delayed
      insertion of a polyetheretherketone cranioplasty for reconstruction of the
      cranial defect. 

PMID- 25383157
TI  - Component approach to the temporomandibular joint and coronoid process.
AB  - Reconstruction of the temporomandibular joint (TMJ) region is challenging. The
      conventional direct preauricular incision permits only limited access to the TMJ
      and surrounding structures, therefore risking injury to the facial nerve during
      retraction. The ideal approach allows sufficient exposure, preservation of
      underlying neurovascular structures, and achieves an optimal aesthetic outcome.
      We describe a preauricular posttragal incision with a superficial
      musculoaponeurotic system flap to allow wide exposure of the zygomatic arch, TMJ,
      condyle, and coronoid process. We postulate that this approach improves access,
      lessens the amount of retraction required, and creates a more inconspicuous scar.

PMID- 25383156
TI  - Successful Treatment of the Traumatic Orbital Apex Syndrome due to Direct Bone
      Compression.
AB  - Orbital apex syndrome is an uncommon but severe ocular complication of
      craniomaxillofacial fracture. The optimal treatment strategy for this very rare
      traumatic syndrome has not been well established. We present a case in which
      traumatic orbital apex syndrome was caused by direct compression from the
      displaced fracture segments. Visual and extraocular function both improved
      quickly after emergency decompression surgery. This case suggests that managing
      the direct type of traumatic orbital apex syndrome with craniomaxillofacial
      fracture with a combination of urgent reduction of impinging bone and
      decompression of affected nerves is an effective strategy. 

PMID- 25383158
TI  - Custom-Made Finger Guard to Prevent Wire-Stick Injury to the Operator's Finger
      while Performing Intermaxillary Fixation.
AB  - The treatment of maxillofacial fractures involves different methods from bandages
      and splinting to methods of open reduction and internal fixation and usually
      requires control of the dental occlusion with the help of intermaxillary fixation
      (IMF). Different wiring techniques have been used to aid in IMF including
      placement of custom-made arch bars, eyelet etc. However, these wiring techniques
      are with a constant danger of trauma to the surgeon's fingers by their sharp
      ends. Though there exist a variety of commercially available barrier products and
      customized techniques to prevent wire-stick injury, cost factor, touch
      sensitivity, and comfort aspect restrain their acquirement and exploit. This
      technical note describes the construction of a simple and economical finger guard
      made of soft thermoplastic material that provides an added protection to fingers
      from wire-stick type injuries, and its flexible nature permits a comfortable
      finger flexion movement and acceptable touch sensitivity. This is a simple,
      economical, reusable puncture, and cut-resistance figure guard by which we can
      avoid wire-stick type injury to the operator's fingers during wiring technique. 

PMID- 25383159
TI  - Fracture of the coronoid process associated with frontosphenoidal fractures.
AB  - Coronoid process fractures are rarely encountered, commonly undiagnosed, usually
      asymptomatic, and most commonly treated conservatively, hence very little written
      about. We present two cases of coronoid process fractures with associated
      frontosphenoidal injuries. 

PMID- 25383160
TI  - ROTATIONAL GRADIENT FIELD FOR INTERPOLATION OF FIBER ORIENTATION DISTRIBUTION IN
      CONNECTIVITY ANALYSIS.
AB  - Advances in diffusion weighted MR imaging have made it possible to non-invasively
      study the structral connectivity of human brains at high resolution. To model
      crossing fibers in white matter, a popular choice is the reconstruction of fiber
      orientation distributions (FODs) from diffusion data. For this sophiscated image
      representation of brain connectivity, classical image operations such as
      differentiation and interpolation must be redefined. In this paper, we introduce
      rotational gradient fields (RGF) as the spatial differential of FODs'
      orientations. By taking into accout the rotational effect of traveling in the
      RGF, an FOD at one location can be transported and aligned with the FOD at the
      target location. We propose a method for inducing RGFs with FOD metrics. We also
      show how RGFs can be used for interpolation, yielding intuitively more reasonable
      results than the Frechet mean on the unit sphere in a Hilbert space [1].

PMID- 25383161
TI  - Blank-comparison matching-to-sample reveals a false positive symmetry test in a
      capuchin monkey.
AB  - A positive symmetry test result was obtained with a capuchin monkey that had
      previously exhibited virtually errorless AB and BA arbitrary matching-to-sample
      (MTS) with different stimuli. The symmetry test (BA) followed the acquisition of
      a new AB relation. It seemed possible, however, that the positive result could
      have occurred through the exclusion of previously defined comparison stimuli and
      not because the new AB and BA relations had the property of symmetry. To assess
      this possibility, a blank-comparison MTS procedure was implemented that permitted
      the separate assessment of select and reject (i.e., exclusion) control with both
      baseline and BA matching relations. In this assessment, the monkey did not
      exhibit reliable BA matching when exclusion was not possible, thus showing that
      the symmetry result was a false positive. However, the study demonstrated the
      feasibility of using a blank comparison MTS procedure with capuchins. The present
      results may set the stage for more successful methodology for establishing
      desired forms of relational stimulus control in capuchins and ultimately
      improving the assessment of relational learning capacity in that species, other
      nonhuman species, and nonverbal humans.

PMID- 25383162
TI  - Elucidating Structural Features of an Entirely Carbohydrate Cancer Vaccine
      Construct Employing Circular Dichroism and Fluorescent Labeling.
AB  - The zwitterionic polysaccharide PS A1 from anaerobe Bacteroides fragilis ATCC
      25285/NCTC 9343 is known to elicit a T-cell-dependent, major histocompatibility
      complex class II (MHCII) immune response through a correspondingly similar
      protein-antigen-based mechanism/pathway. The biological activity of PS A1 is
      known to arise from alternating charged motifs on adjacent monosaccharides
      comprising a tetrameric repeating oligomeric unit creating an alpha-helical
      secondary structure. However, we have learned that this alpha-helical structural
      characteristic may not play a role in immune activation. Paradoxically, our
      current knowledge of structure - activity relationships (SARs) with
      electrostatically charged polysaccharides has become more clearly defined, yet a
      lack of tools/probes for measuring dynamic structural changes hinders progress in
      carbohydrate-based vaccine development. Site- and region-specific structural
      modifications of PS A1, followed by conjugation with a known carbohydrate cancer
      antigen, the Thomsen-nouveau (Tn = alpha-D-GalNAc-OSer/Thr) antigen, does not
      alter antibody isotype switching ability and leads to specific IgG3 antibodies in
      C57BL/6 mice. Circular dichroism (CD) and studies using fluorescently labeled PS
      A1, described herein, reveal information pertaining to structure - activity
      relationships and the nature of Tn conjugation to chemically modified PS A1. The
      CD spectra of a Tn-PS A1 construct at 8.5 >= pH <= 3.5 illustrates complete loss
      of alpha-helical character while spectra obtained in the 3.6 <= pH >= 8.4 range
      denotes minimal alpha-helicity in comparison to naturally occurring PS A1.
      Temperatures exceeding 60  degrees C reveal complete loss of helical character.
      Two methods for Alexa Fluor488(r) fluorescent labeling studies of chemically
      oxidized PS A1 have given rise to percent conjugation values (% loading)
      calculated to be on average 35 Tn molecules bound. Combined, our results argue
      that altering the structure of PS A1, without chemically modifying the
      electrostatic charge character, does not alter immune response/recognition in
      mice. These findings have important implications for the design of entirely
      carbohydrate-based vaccine constructs.

PMID- 25383164
TI  - Human osteoblasts within soft peptide hydrogels promote mineralisation in vitro.
AB  - Biomaterials that provide three-dimensional support networks for the culture of
      cells are being developed for a wide range of tissue engineering applications
      including the regeneration of bone. This study explores the potential of the
      versatile ionic-complementary peptide, FEFEFKFK, for such a purpose as this
      peptide spontaneously self-assembles into beta-sheet-rich fibres that
      subsequently self-associate to form self-supporting hydrogels. Via simple
      live/dead cell assays, we demonstrated that 3 wt% hydrogels were optimal for the
      support of osteoblast cells. We went on to show that these cells are not only
      viable within the three-dimensional hydrogel but they also proliferate and
      produce osteogenic key proteins, that is, they behave like in vivo bone cells,
      over the 14-day period explored here. The gel elasticity increased over time when
      cells were present - in comparison to a decrease in control samples - indicating
      the deposition of matrix throughout the peptide scaffold. Moreover, significant
      quantities of calcium phosphate were deposited. Collectively, these data
      demonstrate that ionic-complementary octapeptides offer a suitable three
      dimensional environment for osteoblastic cell function. 

PMID- 25383163
TI  - Synthetic Flavonoids, Aminoisoflavones: Interaction and Reactivity with Metal
      Free and Metal-Associated Amyloid-beta Species.
AB  - Metal ion homeostasis in conjunction with amyloid-beta (Abeta) aggregation in the
      brain has been implicated in Alzheimer's disease (AD) pathogenesis. To uncover
      the interplay between metal ions and Abeta peptides, synthetic, multifunctional
      small molecules have been employed to modulate Abeta aggregation in vitro.
      Naturally occurring flavonoids have emerged as a valuable class of compounds for
      this purpose due to their ability to modulate both metal-free and metal-induced
      Abeta aggregation. Although, flavonoids have shown anti-amyloidogenic effects,
      the structural moieties of flavonoids responsible for such reactivity have not
      been fully identified. In order to understand the structure-interaction
      reactivity relationship within the flavonoid family for metal-free and metal
      associated Abeta, we designed, synthesized, and characterized a set of isoflavone
      derivatives, aminoisoflavones (1-4), that displayed reactivity (i.e., modulation
      of Abeta aggregation) in vitro. NMR studies revealed a potential binding site for
      aminoisoflavones between the N-terminal loop and central helix on prefibrillar
      Abeta different from the non-specific binding observed for other flavonoids. The
      absence or presence of the catechol group differentiated the binding affinities
      and enthalpy/entropy balance between aminoisoflavones and Abeta. Furthermore,
      having a catechol group influenced the binding mode with fibrillar Abeta.
      Inclusion of additional substituents moderately tuned the impact of
      aminoisoflavones on Abeta aggregation. Overall, through these studies, we
      obtained valuable insights on the requirements for parity among metal chelation,
      intermolecular interactions, and substituent variation for Abeta interaction.

PMID- 25383165
TI  - Rapid prototyped porous nickel-titanium scaffolds as bone substitutes.
AB  - While calcium phosphate-based ceramics are currently the most widely used
      materials in bone repair, they generally lack tensile strength for initial load
      bearing. Bulk titanium is the gold standard of metallic implant materials, but
      does not match the mechanical properties of the surrounding bone, potentially
      leading to problems of fixation and bone resorption. As an alternative, nickel
      titanium alloys possess a unique combination of mechanical properties including a
      relatively low elastic modulus, pseudoelasticity, and high damping capacity,
      matching the properties of bone better than any other metallic material. With the
      ultimate goal of fabricating porous implants for spinal, orthopedic and dental
      applications, nickel-titanium substrates were fabricated by means of selective
      laser melting. The response of human mesenchymal stromal cells to the nickel
      titanium substrates was compared to mesenchymal stromal cells cultured on
      clinically used titanium. Selective laser melted titanium as well as surface
      treated nickel-titanium and titanium served as controls. Mesenchymal stromal
      cells had similar proliferation rates when cultured on selective laser melted
      nickel-titanium, clinically used titanium, or controls. Osteogenic
      differentiation was similar for mesenchymal stromal cells cultured on the
      selected materials, as indicated by similar gene expression levels of bone
      sialoprotein and osteocalcin. Mesenchymal stromal cells seeded and cultured on
      porous three-dimensional selective laser melted nickel-titanium scaffolds
      homogeneously colonized the scaffold, and following osteogenic induction, filled
      the scaffold's pore volume with extracellular matrix. The combination of bone
      related mechanical properties of selective laser melted nickel-titanium with its
      cytocompatibility and support of osteogenic differentiation of mesenchymal
      stromal cells highlights its potential as a superior bone substitute as compared
      to clinically used titanium. 

PMID- 25383166
TI  - Biological effects of soft denture reline materials on L929 cells in vitro.
AB  - Soft denture reline materials have been developed to help patients when their
      oral mucosa is damaged or affected due to ill-fitting dentures or post-implant
      surgery. Although reports have indicated that these materials leach monomers and
      other components that do affect their biocompatibility, there is little
      information on what cell molecules may be implicated in these material/tissue
      interactions. The biocompatibility of six soft liners (Ufi Gel P, Sofreliner S,
      Durabase Soft, Trusoft, Softone and Coe Comfort) was evaluated using a mouse
      fibroblast cell line, L929. Within 2 h of material disc preparation, each of the
      materials was exposed by direct contact to L929 cells for periods of 24 and 48 h.
      The effect of this interaction was assessed by alamarBlue assay (for cell
      survival). The expression of integrin alpha5beta1 and transforming growth factor
      beta1 was also assessed using plate assays such as enzyme-linked immunosorbent
      assay. Trusoft, Softone and Coe Comfort showed significantly reduced cell
      survival compared with the other soft lining materials at each incubation period.
      Furthermore, there were significant differences with these same materials in the
      expression of both integrin alpha5beta1 and transforming growth factor beta1.
      Soft liner materials may affect cell viability and cellular proteins that have
      important roles in wound healing and the preservation of cell viability and
      function in the presence of environmental challenges and stresses. 

PMID- 25383167
TI  - Co-cultured tissue-specific scaffolds for tendon/bone interface engineering.
AB  - The tendon/ligament-to-bone interface has a complex organization to enable
      transfer of forces through the tendon/ligament to the bone. The purpose of this
      study is to create a co-culture environment enabling a tissue-specific tendon
      region and tissue-specific bone region on a degradable scaffold, using NIH 3T3
      fibroblast-deposited extracellular matrix and MC 3T3 osteoblast-deposited
      extracellular matrix, respectively. Before full characterization of the deposited
      extracellular matrix coating can be analyzed, co-culture parameters including
      culture medium and seeding technique should be addressed. An appropriate medium
      formulation was developed to reduce fibroblast to osteoblast mineralization by
      adjusting beta-glycerophosphate concentrations. Standard growth medium with fetal
      bovine serum + 3 mM beta-glycerophosphate + 25 ug/mL ascorbic acid was found to
      be the most suitable formulation evaluated in these study conditions. Seeding and
      cell migration studies of co-cultured fibroblast- and osteoblast-specific
      scaffolds were performed to identify whether tissue regions could be created on
      the scaffold. Fibroblast and osteoblast regions were successfully seeded and
      little to no cell migration was observed up to 42 h after seeding. Finally, a
      preliminary analysis of basic extracellular matrix components was measured in the
      fibroblast, osteoblast, and transition regions. Tissue-specific DNA,
      glycosaminoglycan, and collagen were found in uniform amounts on the scaffolds
      and were not different significantly between scaffold regions. In conclusion,
      initial steps to create tissue-specific fibroblast and osteoblast regions on a
      degradable scaffold were successful in preparation for further characterization
      investigations as a tendon-to-bone interface scaffold. 

PMID- 25383168
TI  - Dynamic cell culture on calcium phosphate microcarriers for bone tissue
      engineering applications.
AB  - Developing appropriate cell culturing techniques to populate scaffolds has become
      a great challenge in tissue engineering. This work describes the use of spinner
      flask dynamic cell cultures to populate hydroxyapatite microcarriers for bone
      tissue engineering. The microcarriers were obtained through the emulsion of a
      self-setting aqueous alpha-tricalcium phosphate slurry in oil. After setting,
      hydroxyapatite microcarriers were obtained. The incorporation of gelatin in the
      liquid phase of the alpha-tricalcium phosphate slurry allowed obtaining hybrid
      gelatin/hydroxyapatite-microcarriers. Initial cell attachment on the
      microcarriers was strongly influenced by the speed of the dynamic culture,
      achieving higher attachment at low speed (40 r/min) as compared to high speed (80
      r/min). Under moderate culture speeds (40 r/min), the number of cells present in
      the culture as well as the number of microcarrier-containing cells considerably
      increased after 3 days, particularly in the gelatin-containing microcarriers. At
      longer culture times in dynamic culture, hydroxyapatite-containing microcarriers
      formed aggregates containing viable and extracellular matrix proteins, with a
      significantly higher number of cells compared to static cultures. 

PMID- 25383169
TI  - The efficacy of cetuximab in a tissue-engineered three-dimensional in vitro model
      of colorectal cancer.
AB  - The preclinical development process of chemotherapeutic drugs is often carried
      out in two-dimensional monolayer cultures. However, a considerable amount of
      evidence demonstrates that two-dimensional cell culture does not accurately
      reflect the three-dimensional in vivo tumour microenvironment, specifically with
      regard to gene expression profiles, oxygen and nutrient gradients and
      pharmacokinetics. With this objective in mind, we have developed and established
      a physiologically relevant three-dimensional in vitro model of colorectal cancer
      based on the removal of interstitial fluid from collagen type I hydrogels. We
      employed the RAFTTM (Real Architecture For 3D Tissue) system for producing three
      dimensional cultures to create a controlled reproducible, multiwell testing
      platform. Using the HT29 and HCT116 cell lines to model epidermal growth factor
      receptor expressing colorectal cancers, we characterized three-dimensional cell
      growth and morphology in addition to the anti-proliferative effects of the anti
      epidermal growth factor receptor chemotherapeutic agent cetuximab in comparison
      to two-dimensional monolayer cultures. Cells proliferated well for 14 days in
      three-dimensional culture and formed well-defined cellular aggregates within the
      concentrated collagen matrix. Epidermal growth factor receptor expression levels
      revealed a twofold and threefold increase in three-dimensional cultures for both
      HT29 and HCT116 cells in comparison to two-dimensional monolayers, respectively
      (p < 0.05; p < 0.01). Cetuximab efficacy was significantly lower in HT29 three
      dimensional cultures in comparison to two-dimensional monolayers, whereas HCT116
      cells in both two-dimension and three-dimension were non-responsive to treatment
      in agreement with their KRAS mutant status. In summary, these results confirm the
      use of a three-dimensional in vitro cancer model as a suitable drug-screening
      platform for in vitro pharmacological testing. 

PMID- 25383171
TI  - Electrospun silk fibroin fiber diameter influences in vitro dermal fibroblast
      behavior and promotes healing of ex vivo wound models.
AB  - Replicating the nanostructured components of extracellular matrix is a target for
      dermal tissue engineering and regenerative medicine. Electrospinning Bombyx mori
      silk fibroin (BMSF) allows the production of nano- to microscale fibrous
      scaffolds. For BMSF electrospun scaffolds to be successful, understanding and
      optimizing the cellular response to material morphology is essential. Primary
      human dermal fibroblast response to nine variants of BMSF scaffolds composed of
      nano- to microscale fibers ranging from ~250 to ~1200 nm was assessed in vitro
      with regard to cell proliferation, viability, cellular morphology, and gene
      expression. BMSF support of epithelial migration was then assessed through
      utilization of a novel ex vivo human skin wound healing model. Scaffolds composed
      of the smallest diameter fibers, ~250 -300 nm, supported cell proliferation
      significantly more than fibers with diameters approximately 1 MUm (p < 0.001).
      Cell morphology was observed to depart from a stellate morphology with numerous
      cell -fiber interactions to an elongated, fiber-aligned morphology with
      interaction predominately with single fibers. The expressions of extracellular
      matrix genes, collagen types I and III (p < 0.001), and proliferation markers,
      proliferating cell nuclear antigen (p < 0.001), increased with decreasing fiber
      diameter. The re-epithelialization of ex vivo wound models was significantly
      improved with the addition of BMSF electrospun scaffolds, with migratory
      keratinocytes incorporated into scaffolds. BMSF scaffolds with nanofibrous
      architectures enhanced proliferation in comparison to microfibrous scaffolds and
      provided an effective template for migratory keratinocytes during re
      epithelialization. The results may aid in the development of effective BMSF
      electrospun scaffolds for wound healing applications. 

PMID- 25383170
TI  - A review on the use of cell therapy in the treatment of tendon disease and
      injuries.
AB  - Tendon disease and injuries carry significant morbidity worldwide in both
      athletic and non-athletic populations. It is estimated that tendon injuries
      account for 30%-50% of all musculoskeletal injuries globally. Current treatments
      have been inadequate in providing an accelerated process of repair resulting in
      high relapse rates. Modern concepts in tissue engineering and regenerative
      medicine have led to increasing interest in the application of cell therapy for
      the treatment of tendon disease. This review will explore the use of cell
      therapy, by bringing together up-to-date evidence from in vivo human and animal
      studies, and discuss the issues surrounding the safety and efficacy of its use in
      the treatment of tendon disease. 

PMID- 25383172
TI  - Prospective isolation of human bone marrow stromal cell subsets: A comparative
      study between Stro-1-, CD146- and CD105-enriched populations.
AB  - Stro-1 has proved an efficacious marker for enrichment of skeletal stem and
      progenitor cells although isolated populations remain heterogeneous, exhibiting
      variable colony-forming efficiency and osteogenic differentiation potential. The
      emerging findings that skeletal stem cells originate from adventitial reticular
      cells have brought two further markers to the fore including CD146 and CD105
      (both primarily endothelial and perivascular). This study has compared CD146-,
      CD105- and Stro-1 (individual and in combination)-enriched human bone marrow
      stromal cell subsets and assessed whether these endothelial/perivascular markers
      offer further selection over conventional Stro-1. Fluorescent cell sorting
      quantification showed that CD146 and CD105 both targeted smaller (2.22% +/- 0.59%
      and 6.94% +/- 1.34%, respectively) and potentially different human bone marrow
      stromal cell fractions compared to Stro-1 (16.29% +/- 0.78%). CD146+, but not
      CD105+, cells exhibited similar alkaline phosphatase-positive colony-forming
      efficiency in vitro and collagen/proteoglycan deposition in vivo to Stro-1+
      cells. Molecular analysis of a number of select osteogenic and potential osteo
      predictive genes including ALP, CADM1, CLEC3B, DCN, LOXL4, OPN, POSTN and SATB2
      showed Stro-1+ and CD146+ populations possessed similar expression profiles. A
      discrete human bone marrow stromal cell fraction (2.04% +/- 0.41%) exhibited
      positive immuno-labelling for both Stro-1 and CD146. The data presented here show
      that CD146+ populations are comparable but not superior to Stro-1+ populations.
      However, this study demonstrates the critical need for new candidate markers with
      which to isolate homogeneous skeletal stem cell populations or skeletal stem cell
      populations which exhibit homogeneous in vitro/in vivo characteristics, for
      implementation within tissue engineering and regenerative medicine strategies. 

PMID- 25383173
TI  - Quantitative assessment of barriers to the clinical development and adoption of
      cellular therapies: A pilot study.
AB  - There has been a large increase in basic science activity in cell therapy and a
      growing portfolio of cell therapy trials. However, the number of industry
      products available for widespread clinical use does not match this magnitude of
      activity. We hypothesize that the paucity of engagement with the clinical
      community is a key contributor to the lack of commercially successful cell
      therapy products. To investigate this, we launched a pilot study to survey
      clinicians from five specialities and to determine what they believe to be the
      most significant barriers to cellular therapy clinical development and adoption.
      Our study shows that the main concerns among this group are cost-effectiveness,
      efficacy, reimbursement, and regulation. Addressing these concerns can best be
      achieved by ensuring that future clinical trials are conducted to adequately
      answer the questions of both regulators and the broader clinical community. 

PMID- 25383174
TI  - Scanning electron microscopical observation of an osteoblast/osteoclast co
      culture on micropatterned orthopaedic ceramics.
AB  - In biomaterial engineering, the surface of an implant can influence cell
      differentiation, adhesion and affinity towards the implant. On contact with an
      implant, bone marrow-derived mesenchymal stromal cells demonstrate
      differentiation towards bone forming osteoblasts, which can improve
      osteointegration. The process of micropatterning has been shown to improve
      osteointegration in polymers, but there are few reports surrounding ceramics. The
      purpose of this study was to establish a co-culture of bone marrow-derived
      mesenchymal stromal cells with osteoclast progenitor cells and to observe the
      response to micropatterned zirconia toughened alumina ceramics with 30 um
      diameter pits. The aim was to establish whether the pits were specifically
      bioactive towards osteogenesis or were generally bioactive and would also
      stimulate osteoclastogenesis that could potentially lead to osteolysis. We
      demonstrate specific bioactivity of micropatterns towards osteogenesis, with more
      nodule formation and less osteoclastogenesis compared to planar controls. In
      addition, we found that that macrophage and osteoclast-like cells did not
      interact with the pits and formed fewer full-size osteoclast-like cells on the
      pitted surfaces. This may have a role when designing ceramic orthopaedic
      implants. 

PMID- 25383176
TI  - Interphotoreceptor matrix-poly(epsilon-caprolactone) composite scaffolds for
      human photoreceptor differentiation.
AB  - Tissue engineering has been widely applied in different areas of regenerative
      medicine, including retinal regeneration. Typically, artificial biopolymers
      require additional surface modification (e.g. with arginine-glycine-aspartate
      containing peptides or adsorption of protein, such as fibronectin), before cell
      seeding. Here, we describe an alternative approach for scaffold design: the
      manufacture of hybrid interphotoreceptor matrix-poly (epsilon-caprolactone)
      scaffolds, in which the insoluble extracellular matrix of the retina is
      incorporated into a biodegradable polymer well suited for transplantation. The
      incorporation of interphotoreceptor matrix did not change the topography of
      polycaprolactone film, although it led to a slight increase in hydrophilic
      properties (water contact angle measurements). This hybrid scaffold provided
      sufficient stimuli for human retinal progenitor cell adhesion and inhibited
      proliferation, leading to differentiation toward photoreceptor cells (expression
      of Crx, Nrl, rhodopsin, ROM1). This scaffold may be used for transplantation of
      retinal progenitor cells and their progeny to treat retinal degenerative
      disorders. 

PMID- 25383177
TI  - The effect of different biologic and biosynthetic wound covers on keratinocyte
      growth, stratification and differentiation in vitro.
AB  - The purpose of this study was to compare, by means of in vitro cultivation
      technique, five marketed brands of wound covers used in the treatment of burns
      and other skin defects (Biobrane((r)), Suprathel((r)), Veloderm((r)), Xe
      Derma((r)), and Xenoderm((r))) for their ability to stimulate the keratinocyte
      growth, stratification, and differentiation. In three independent experiments,
      human keratinocytes were grown on the tested covers in organotypic cultures by
      the 3T3 feeder layer technique. Vertical paraffin sections of the wound covers
      with keratinocytes were processed using hematoxylin-eosin staining and
      immunostaining for involucrin. Keratinocyte populations on the dressings were
      assessed for (1) number of keratinocyte strata (primary variable), (2)
      quantitative growth, (3) thickness of the keratinocyte layer, and (4) cell
      differentiation. The Xe-Derma wound cover provided the best support to
      keratinocyte proliferation and stratification, with the number of keratinocyte
      strata significantly (p < 0.05) higher in comparison to all products studied,
      except Xenoderm. However, in contrast to Xe-Derma, Xenoderm did not significantly
      differ from the other dressings. The results of this in vitro study show that the
      brands based on porcine dermal matrix possess the strongest effect on
      keratinocyte proliferation and stratification. The distinctive position of Xe
      Derma may be related to its composition, where natural dermal fibers form a
      smooth surface, similar to the basement membrane. Furthermore, the results
      indicate that in vitro evaluation of effects on epithelial growth may accelerate
      the development of new bio-engineering-based wound covers. 

PMID- 25383175
TI  - Directed differentiation of induced pluripotent stem cells into chondrogenic
      lineages for articular cartilage treatment.
AB  - In recent years, increases in the number of articular cartilage injuries caused
      by environmental factors or pathological conditions have led to a notable rise in
      the incidence of premature osteoarthritis. Osteoarthritis, considered a disease
      of civilization, is the leading cause of disability. At present, standard methods
      for treating damaged articular cartilage, including autologous chondrocyte
      implantation or microfracture, are short-term solutions with important side
      effects. Emerging treatments include the use of induced pluripotent stem cells, a
      technique that could provide a new tool for treatment of joint damage. However,
      research in this area is still early, and no optimal protocol for transforming
      induced pluripotent stem cells into chondrocytes has yet been established.
      Developments in our understanding of cartilage developmental biology, together
      with the use of modern technologies in the field of tissue engineering, provide
      an opportunity to create a complete functional model of articular cartilage. 

PMID- 25383180
TI  - Extending the boundaries of family medicine to perform manual procedures.
AB  - A recent survey by Menahem and colleagues revealed that 65% of the surveyed
      primary care physicians reported that they performed any minor surgical
      procedures, and 46% reported performance of any musculoskeletal injections. Lack
      of allocated time and lack of training were the main reported barriers
      confronting higher performance rates. Healthcare systems are shifting large
      chunks of traditional hospital-centered activities to competent and comprehensive
      community-based structures. These changes are very well aligned with key trends
      in modern consumerism that prefer a close to home availability of medical
      services. Minor surgical procedures and musculoskeletal injections are good
      examples of medical activities that had been performed mainly by hospital and
      community based specialists. The syllabus of specialty training in Family
      Medicine in Israel includes these skills and trainees should acquire them during
      the residency program. We estimate that hundreds of family physicians obtain
      different levels of such training. Yet, only few family physicians have allocated
      protected time for performance of the procedures. For the skilled physician,
      performance of such relatively simple procedures extends his professional
      boundaries and the comprehensiveness of his service. For the healthcare system
      the "extra effort" and investment needed for performance of minor surgical
      procedures in primary care clinics is small. The results of the present study
      reflect on wider issues of care delivery. This study highlights the need for
      formalized and documented training of family physicians together with allocation
      of managerial and technical requirements needed to encourage these and similar
      medically and economically justified endeavors that seem to be perfectly aligned
      with the wishes of healthcare consumers. 

PMID- 25383181
TI  - Developing sustainable software solutions for bioinformatics by the " Butterfly"
      paradigm.
AB  - Software design and sustainable software engineering are essential for the long
      term development of bioinformatics software. Typical challenges in an academic
      environment are short-term contracts, island solutions, pragmatic approaches and
      loose documentation. Upcoming new challenges are big data, complex data sets,
      software compatibility and rapid changes in data representation. Our approach to
      cope with these challenges consists of iterative intertwined cycles of
      development (" Butterfly" paradigm) for key steps in scientific software
      engineering. User feedback is valued as well as software planning in a
      sustainable and interoperable way. Tool usage should be easy and intuitive. A
      middleware supports a user-friendly Graphical User Interface (GUI) as well as a
      database/tool development independently. We validated the approach of our own
      software development and compared the different design paradigms in various
      software solutions. 

PMID- 25383178
TI  - A review of adipocyte lineage cells and dermal papilla cells in hair follicle
      regeneration.
AB  - Alopecia is an exceedingly prevalent problem effecting men and women of all ages.
      The standard of care for alopecia involves either transplanting existing hair
      follicles to bald areas or attempting to stimulate existing follicles with
      topical and/or oral medication. Yet, these treatment options are fraught with
      problems of cost, side effects, and, most importantly, inadequate long-term hair
      coverage. Innovative cell-based therapies have focused on the dermal papilla cell
      as a way to grow new hair in previously bald areas. However, despite this
      attention, many obstacles exist, including retention of dermal papilla inducing
      ability and maintenance of dermal papilla productivity after several passages of
      culture. The use of adipocyte lineage cells, including adipose-derived stem
      cells, has shown promise as a cell-based solution to regulate hair regeneration
      and may help in maintaining or increasing dermal papilla cells inducing hair
      ability. In this review, we highlight recent advances in the understanding of the
      cellular contribution and regulation of dermal papilla cells and summarize
      adipocyte lineage cells in hair regeneration. 

PMID- 25383182
TI  - Simple, biologically-constrained CA1 pyramidal cell models using an intact, whole
      hippocampus context.
AB  - The hippocampus is a heavily studied brain structure due to its involvement in
      learning and memory. Detailed models of excitatory, pyramidal cells in
      hippocampus have been developed using a range of experimental data. These models
      have been used to help us understand, for example, the effects of synaptic
      integration and voltage gated channel densities and distributions on cellular
      responses. However, these cellular outputs need to be considered from the
      perspective of the networks in which they are embedded. Using modeling
      approaches, if cellular representations are too detailed, it quickly becomes
      computationally unwieldy to explore large network simulations. Thus, simple
      models are preferable, but at the same time they need to have a clear,
      experimental basis so as to allow physiologically based understandings to emerge.
      In this article, we describe the development of simple models of CA1 pyramidal
      cells, as derived in a well-defined experimental context of an intact, whole
      hippocampus preparation expressing population oscillations. These models are
      based on the intrinsic properties and frequency-current profiles of CA1 pyramidal
      cells, and can be used to build, fully examine, and analyze large networks. 

PMID- 25383183
TI  - The 'SAR Matrix' method and its extensions for applications in medicinal
      chemistry and chemogenomics.
AB  - We describe the 'Structure-Activity Relationship (SAR) Matrix' (SARM) methodology
      that is based upon a special two-step application of the matched molecular pair
      (MMP) formalism. The SARM method has originally been designed for the extraction,
      organization, and visualization of compound series and associated SAR information
      from compound data sets. It has been further developed and adapted for other
      applications including compound design, activity prediction, library extension,
      and the navigation of multi-target activity spaces. The SARM approach and its
      extensions are presented here in context to introduce different types of
      applications and provide an example for the evolution of a computational
      methodology in pharmaceutical research. 

PMID- 25383184
TI  - Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats
      with focal ischemia.
AB  - The pursuit of targeting multiple pathways in the ischemic cascade of cerebral
      stroke is a promising treatment option. We examined the regenerative potential of
      conditioned medium derived from rat and human apoptotic mononuclear cells (MNC),
      rMNC (apo sec) and hMNC (apo sec), in experimental stroke. We performed middle
      cerebral artery occlusion on Wistar rats and administered apoptotic MNC
      secretomes intraperitoneally in two experimental settings. Ischemic lesion
      volumes were determined 48 hours after cerebral ischemia. Neurological
      evaluations were performed after 6, 24 and 48 hours. Immunoblots were conducted
      to analyze neuroprotective signal-transduction in human primary glia cells and
      neurons. Neuronal sprouting assays were performed and neurotrophic factors in
      both hMNC (apo sec) and rat plasma were quantified using ELISA. Administration of
      rat as well as human apoptotic MNC-secretomes significantly reduced ischemic
      lesion volumes by 36% and 37%, respectively. Neurological examinations revealed
      improvement after stroke in both treatment groups. Co-incubation of human
      astrocytes, Schwann cells and neurons with hMNC (apo sec) resulted in activation
      of several signaling cascades associated with the regulation of cytoprotective
      gene products and enhanced neuronal sprouting in vitro. Analysis of neurotrophic
      factors in hMNC (apo sec) and rat plasma revealed high levels of brain derived
      neurotrophic factor (BDNF). Our data indicate that apoptotic MNC-secretomes
      elicit neuroprotective effects on rats that have undergone ischemic stroke. 

PMID- 25383185
TI  - CyKEGGParser: tailoring KEGG pathways to fit into systems biology analysis
      workflows.
AB  - The KEGG pathway database is a widely accepted source for biomolecular pathway
      maps. In this paper we present the CyKEGGParser app (
      http://apps.cytoscape.org/apps/cykeggparser) for Cytoscape 3 that allows
      manipulation with KEGG pathway maps. Along with basic functionalities for pathway
      retrieval, visualization and export in KGML and BioPAX formats, the app provides
      unique features for computer-assisted adjustment of inconsistencies in KEGG
      pathway KGML files and generation of tissue- and protein-protein interaction
      specific pathways. We demonstrate that using biological context-specific KEGG
      pathways created with CyKEGGParser makes systems biology analysis more sensitive
      and appropriate compared to original pathways. 

PMID- 25383187
TI  - Case Report: Testicular failure possibly associated with chronic use of
      methylphenidate.
AB  - Methylphenidate is a commonly prescribed treatment for attention deficit
      hyperactivity disorder (ADHD). However, little is known about its adverse effects
      on the male reproductive system. We report a 20-year-old male patient whose chief
      complaint was of delayed puberty. He spoke in a high-pitched voice and complained
      of lack of body hair, impaired libido, inadequate erectile function, chronic
      fatigue, and low energy. He had been treated with methylphenidate as an infant
      and had continued treatment for 17 years. On examination, the patient was lean
      and visibly lacked facial or body hair. He further explained that he had never
      been able to grow underarm or facial hair and that he was often mistakenly
      considered a young teenager rather than a 20-year-old. The patient's genitalia
      were categorized as Tanner Stage 2. Laboratory studies confirmed low serum
      follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone
      levels. The patient was given exogenous testosterone supplementation with pellets
      and human chorionic gonadotropin to maintain testicular size. After 4 months his
      symptoms improved and he demonstrated signs of puberty. Our goal is to further
      elucidate the possible impact of methylphenidate on the male reproductive system.

PMID- 25383186
TI  - Myelin-specific T helper 17 cells promote adult hippocampal neurogenesis through
      indirect mechanisms.
AB  - CD4 (+) T cells provide a neuro-immunological link in the regulation of adult
      hippocampal neurogenesis, but the exact mechanisms underlying enhanced neural
      precursor cell proliferation and the relative contribution of different T helper
      (Th) cell subsets have remained unclear. Here, we explored the proneurogenic
      potential of interleukin 17-producing T helper (Th17) cells, a developmentally
      and functionally distinct Th cell subset that is a key mediator of autoimmune
      neurodegeneration. We found that base-line proliferation of hippocampal precursor
      cells in a T cell-deficient mouse model of impaired hippocampal neurogenesis can
      be restored upon adoptive transfer with homogeneous Th17 populations enriched for
      myelin-reactive T cell receptors. In these experiments, enhanced proliferation
      was independent of direct interactions of infiltrating Th17 cells with precursor
      cells or neighboring cells in the hippocampal neurogenic niche. Complementary
      studies in immunocompetent mice identified several receptors for Th17 cell
      derived cytokines with mRNA expression in hippocampal precursor cells and dentate
      gyrus tissue, suggesting that Th17 cell activity in peripheral lymphoid tissues
      might promote hippocampal neurogenesis through secreted cytokines. 

PMID- 25383188
TI  - Plasmodium falciparum infection rates for some Anopheles spp. from Guinea-Bissau,
      West Africa.
AB  - Presence of Plasmodium falciparum circumsporozoite protein (CSP) was detected by
      enzyme linked immunosorbent assay (ELISA) in a sample of Anopheles gambiae s.s.,
      A. melas and A. pharoensis collected in Guinea-Bissau during October and November
      2009. The percentage of P. falciparum infected samples (10.2% overall) was
      comparable to earlier studies from other sites in Guinea-Bissau (9.6-12.4%). The
      majority of the specimens collected were identified as A. gambiae which had an
      individual infection rate of 12.6 % across collection sites. A small number of
      specimens of A. coluzzii, A. coluzzii x A. gambiae hybrids, A. melas and A.
      pharoensis were collected and had infection rates of 4.3%, 4.1%, 11.1% and 33.3%
      respectively. Despite being present in low numbers in indoor collections, the
      exophilic feeding behaviors of A. melas (N=18) and A. pharoensis (N=6) and high
      infection rates observed in this survey suggest falciparum-malaria transmission
      potential outside of the protection of bed nets. 

PMID- 25383189
TI  - Late cardiac sodium current can be assessed using automated patch-clamp.
AB  - The cardiac late Na (+) current is generated by a small fraction of voltage
      dependent Na (+) channels that undergo a conformational change to a burst-gating
      mode, with repeated openings and closures during the action potential (AP)
      plateau. Its magnitude can be augmented by inactivation-defective mutations,
      myocardial ischemia, or prolonged exposure to chemical compounds leading to drug
      induced (di)-long QT syndrome, and results in an increased susceptibility to
      cardiac arrhythmias. Using CytoPatchTM 2 automated patch-clamp equipment, we
      performed whole-cell recordings in HEK293 cells stably expressing human Nav1.5,
      and measured the late Na (+) component as average current over the last 100 ms of
      300 ms depolarizing pulses to -10 mV from a holding potential of -100 mV, with a
      repetition frequency of 0.33 Hz. Averaged values in different steady-state
      experimental conditions were further corrected by the subtraction of current
      average during the application of tetrodotoxin (TTX) 30 MUM. We show that
      ranolazine at 10 and 30 MUM in 3 min applications reduced the late Na (+) current
      to 75.0 +/- 2.7% (mean +/- SEM, n = 17) and 58.4 +/- 3.5% ( n = 18) of initial
      levels, respectively, while a 5 min application of veratridine 1 MUM resulted in
      a reversible current increase to 269.1 +/- 16.1% ( n = 28) of initial values.
      Using fluctuation analysis, we observed that ranolazine 30 MUM decreased mean
      open probability p from 0.6 to 0.38 without modifying the number of active
      channels n, while veratridine 1 MUM increased n 2.5-fold without changing p. In
      human iPSC-derived cardiomyocytes, veratridine 1 MUM reversibly increased APD90
      2.12 +/- 0.41-fold (mean +/- SEM, n = 6). This effect is attributable to
      inactivation removal in Nav1.5 channels, since significant inhibitory effects on
      hERG current were detected at higher concentrations in hERG-expressing HEK293
      cells, with a 28.9 +/- 6.0% inhibition (mean +/- SD, n = 10) with 50 MUM
      veratridine. 

PMID- 25383190
TI  - Structural characterization of nanofiber silk produced by embiopterans
      (webspinners).
AB  - Embiopterans produce silken galleries and sheets using exceptionally fine silk
      fibers in which they live and breed. In this study, we use electron microscopy
      (EM), Fourier-transform infrared (FT-IR) spectroscopy, wide angle X-ray
      diffraction (WAXD) and solid-state nuclear magnetic resonance (ssNMR) techniques
      to elucidate the molecular level protein structure of webspinner (embiid) silks.
      Silks from two species Antipaluria urichi and Aposthonia ceylonica are studied in
      this work. Electron microscopy images show that the fibers are about 90-100 nm in
      diameter, making webspinner silks among the finest of all known animal silks.
      Structural studies reveal that the silk protein core is dominated by beta-sheet
      structures, and that the protein core is coated with a hydrophobic alkane-rich
      surface coating. FTIR spectra of native embiid silk shows characteristic alkane
      CH2 stretchings near 2800-2900 cm-1, which decrease approximately 50% after
      washing the silk with 2 : 1 CHCl3 : MeOH. Furthermore, 13C ssNMR data shows a
      significant CH2 resonance that is strongly affected by the presence of water,
      supporting the idea that the silk fibers are coated with a hydrocarbon-rich
      layer. Such a layer is likely used to protect the colonies from rain. FTIR data
      also suggests that embiid silks are dominated by beta-sheet secondary structures
      similar to spider and silkworm silk fibers. NMR data confirms the presence of
      beta-sheet nanostructures dominated by serine-rich repetitive regions. A
      deconvolution of the serine Cbeta NMR resonance reveals that approximately 70% of
      all seryl residues exist in a beta-sheet structure. This is consistent with WAXD
      results that suggest webspinner silks are 70% crystalline, which is the highest
      crystalline fraction reported for any animal silks. The work presented here
      provides a molecular level structural picture of silk fibers produced by
      webspinners.

PMID- 25383191
TI  - Electrochemically Created Highly Surface Roughened Ag Nanoplate Arrays for SERS
      Biosensing Applications.
AB  - Highly surface-roughened Ag nanoplate arrays are fabricated using a simple
      electrodeposition and in situ electrocorrosion method with inorganic borate ions
      as capping agent. The electrocorrosion process is induced by a change in the
      local pH value during the electrochemical growth, which is used to intentionally
      carve the electrodeposited structures. The three dimensionally arranged Ag
      nanoplates are integrated with substantial surface-enhanced Raman scattering
      (SERS) hot spots and are free of organic contaminations widely used as shaping
      agents in previous works, making them excellent candidate substrates for SERS
      biosensing applications. The SERS enhancement factor of the rough Ag nanoplates
      is estimated to be > 109. These Ag nanoplate arrays are used for SERS-based
      analysis of DNA hybridization monitoring, protein detection, and virus
      differentiation without any additional surface modifications or labelling. They
      all exhibit an extremely high detection sensitivity, reliability, and
      reproducibility.

PMID- 25383192
TI  - Occurrence and clinical management of moderate-to-severe adverse events during
      drug-resistant tuberculosis treatment: a retrospective cohort study.
AB  - OBJECTIVES: To determine the incidence of symptomatic moderate-to-severe adverse
      events during treatment of drug-resistant tuberculosis, and to compare their risk
      and outcomes by patients' human immunodeficiency virus (HIV) co-infection status.
      METHODS: We conducted a retrospective cohort analysis of patients treated for
      drug-resistant tuberculosis between January 2008 and February 2010. Routinely,
      clinicians monitored and managed patients' response to treatment until its
      completion. Any symptomatic adverse event observed by the clinician or reported
      by the patient was recorded in the standard patient treatment booklet of the
      National Tuberculosis and Leprosy Programme. There were 18 symptomatic adverse
      events routinely monitored. Depending on the nature of the medical intervention
      needed, each was graded as mild, moderate or severe. Data were extracted from the
      patient treatment booklet using a structured form, then descriptive, bivariate
      and Cox proportional hazard analysis performed, stratified by patients' HIV
      infection status. Statistical associations were done at the 5% level of
      significance and reported with 95% confidence intervals. RESULTS: Fifty seven
      (57) patients with drug-resistant tuberculosis were identified, 31 (53%) of whom
      were HIV co-infected. The cumulative incidence of moderate-to-severe adverse
      events was 46 events in 100 patients. HIV co-infected patients experienced more
      moderate-to-severe adverse events compared with the HIV uninfected patients
      (median 3 versus 1 events, p = 0.01). They had a four-fold increase in the
      cumulative hazard of moderate-to-severe adverse events compared with the HIV
      uninfected patients (HR = 4.0, 95% CI 1.5 - 10.5). Moderate-to-severe adverse
      events were the main determinant of a clinician's decision to reduce the dose or
      to stop the suspected offending medicine (RR = 3.8, 95% 1.2-11.8). CONCLUSIONS:
      Moderate-to-severe adverse events are common during drug-resistant tuberculosis
      therapy. They are more likely to occur and to persist in HIV co-infected patients
      than in HIV uninfected patients. Clinicians should employ various strategies for
      preventing drug-induced patient discomfort and harm, such as reducing the dose or
      stopping the suspected offending medicine. Managers of tuberculosis control
      programmes should strengthen pharmacovigilance systems. We recommend a more
      powered study for conclusive risk-factor analysis.

PMID- 25383194
TI  - Developing role models for health in the fire service: a pilot case study.
AB  - OBJECTIVES: The objectives of this case study were to develop role models for
      health in the fire service through knowledge and behaviour change, to improve the
      role models' own health, and to facilitate behaviour change in other firefighters
      through their example. DESIGN: Volunteers interested in improving their own
      health and serving as role models to others in the fire service were identified
      at a statewide Maryland fire service leadership meeting. SETTING: Participants
      worked with the Johns Hopkins Weight Management Center to learn how to improve
      their own health and shared that knowledge with others in their fire departments.
      PARTICIPANTS: Three Maryland fire service leaders were recruited at a leadership
      meeting with the goal of improving their own health and becoming role models. One
      participant dropped out shortly after beginning, while two male participants,
      aged 57 and 61, completed the study. MAIN OUTCOME MEASURES: Quantitative measures
      were collected at baseline and 12 months, and included weight, blood pressure and
      fasting glucose and cholesterol. Semi-structured interviews were conducted
      approximately 14 months postintervention to determine the participants'
      perceptions of their own health and impact on others in the fire service.
      RESULTS: Each participant had biweekly to monthly visits over a one-year period
      to learn the knowledge and skills that would assist him with improving dietary
      behaviours, increasing fitness and achieving a healthy weight. Case study
      participants experienced reductions in body weight (-13% and -11% of total body
      weight), glucose and blood pressure. Qualitative one-on-one interviews conducted
      postintervention with the participants revealed that they embraced their status
      as role models and felt their success inspired other firefighters. Their
      experiences suggest that role models can play an important role in helping
      firefighters increase self-efficacy, self-regulation and social support in the
      workplace environment. CONCLUSIONS: These findings provide promising evidence for
      the use of role models to improve health, especially in the workplace.

PMID- 25383195
TI  - Much more than gastro-enteritis: a severe case of hypo-pituitarism.
AB  - While well described in text books, acute presentations of hypo-pituitarism are
      rare and must be considered when patients present with vague symptoms with poor
      response to standard resuscitation procedures. 

PMID- 25383196
TI  - Hospital-wide infection control practice and Meticillin-resistant Staphylococcus
      aureus (MRSA) in the intensive care unit (ICU): an observational study.
AB  - OBJECTIVES: To estimate trends in infection/colonisation with meticillin
      resistant Staphylococcus aureus (MRSA) in an intensive care unit (ICU). DESIGN:
      Observational study of results of ICU admission and weekly screens for MRSA.
      SETTING AND PARTICIPANTS: All ICU admissions in 2001-2012. INTERVENTIONS: ICU
      admissions were screened for MRSA throughout. In late 2006, screening was
      extended to the whole hospital and extra measures taken in ICU. MAIN OUTCOME
      MEASURES: Prevalence of MRSA in ICU admissions and number acquiring MRSA therein.
      RESULTS: In all, 366 of 6565 admissions to ICU were MRSA positive, including 270
      of 4466 coming from within the hospital in which prevalence increased with time
      prior to transfer to ICU. Prevalence in this group was 9.4% (8.2-10.6) in 2001
      2006, decreasing to 3.4% (2.3-4.5) in 2007-2009 and 1.3% (0.6-2.0) in 2010-2012,
      p < 0.001, due to decreased prevalence in those spending >5 days on wards before
      ICU admission: 18.9% (15.6-22.2) in 2001-2006, 7.1% (4.0-10.2) in 2007-2009 and
      1.6% (0.1-3.1) in 2010-2012, p < 0.001. In addition, 201 patients acquired MRSA
      within ICU, the relative risk being greater when known positives present: 4.34
      (3.98-4.70), p < 0.001. Acquisition rate/1000 bed days decreased from 13.3 (11.2
      15.4) in 2001-2006 to 3.6 (2.6-4.6) in 2007-2012, p < 0.0001. Of 41 ICU-acquired
      MRSA bacteraemias, 38 were in 2001-2006. The risk of bacteraemia in those
      acquiring MRSA decreased from 25% (18.1-31.9) in 2001-2006 to 6.1% (0-12.8)
      thereafter, p = 0.022. CONCLUSIONS: Following better hospital-wide infection
      control, fewer MRSA-positive patients were admitted to ICU with a parallel
      decrease in acquisition therein. Better practice there reduced the risk of
      bacteraemia.

PMID- 25383193
TI  - Anticancer activity and chemoprevention of xenobiotic organosulfurs in
      preclinical model systems.
AB  - There seems to be little doubt that xenobiotic and plant derived organosulfur
      compounds have enormous benefits for in vitro cellular functions and for a
      multitude of diseases, including cancer. Since there are numerous reviews on
      anticancer activities of plant organosulfurs, the focus herein will be on
      alterations associated with xenobiotic organosulfurs. Benefits of 2
      mercaptoethanol (2-Me), N-Acetyl-cysteine, cysteamine, thioproline, piroxicam,
      disulfiram, amifostine, sulindac, celecoxib, oltipraz and their derivates on
      transplanted homologous tumors and on autochthonous cancers with a viral-,
      radiation-, chemical carcinogen-, and undefined-etiology are assessed. Because
      all organosulfurs were not tested for activity in each of the etiology
      categories, comparative evaluations are restricted. In general, all 'appeared' to
      lower the incidence of cancer irrespective of etiology; however, since most of
      these values were determined at ages much younger than at a natural-end-of-life
      age, differences most likely, instead, reflect a delayed initiation and/or a
      slowed progression of tumorigenesis. The poorest, long-term benefits of early
      intervention protocols occurred for viral- and chemical carcinogen-induced
      cancers. In addition, once tumorigenesis was beyond the initiation stage,
      outcomes of organosulfur therapies were extremely poor, indicating that they will
      not be of significant value as stand alone treatments. More importantly, except
      for the lifetime prevention of spontaneous and radiation-induced mammary tumors
      by daily dietary 2-Me, similar life long prevention of tumorigenesis was not
      achieved with other xenobiotics or any of nature's plant organosulfurs. These
      results raise an interesting question: Is the variability in incidence found for
      different organosulfurs associated with (a) their structure, (b) the length of
      the untreated latency period, (c) treatment duration/dose, and/or (d) the
      etiology-inducing agent?

PMID- 25383197
TI  - Retrospective observational study examining indications for hospitalisation among
      haemodialysis patients at one of the Ministry of Health Hospitals in Makkah,
      Saudi Arabia.
AB  - OBJECTIVES: To examine the indications for hospitalisations among haemodialysis
      patients. DESIGN: A retrospective observational study. SETTING: Alnoor Kidney
      Centre in Al Noor Specialist Hospital, Makkah City, Saudi Arabia, which is a
      Ministry of Health hospital. PARTICIPANTS: Participants were prevalent patients
      with end-stage renal disease on regular haemodialysis in 2011, who had received
      haemodialysis for more than three months. Each patient was followed up
      retrospectively, from the first date of initiating haemodialysis to the end of
      2011. MAIN OUTCOME MEASURES: (i) The primary reasons for hospital admissions and
      (ii) risk factors that increase the number of hospital admissions and which
      increase length of stay in hospital. RESULTS: The primary reasons for hospital
      admissions associated with increases in the length of stay in hospital were
      diseases of the circulatory system (which increased hospital bed days by 70%; 95%
      CI: 11-161%; p value = 0.01 compared to all other reasons). The risk factors that
      increased the number of hospital admissions per patient-year at risk were
      increasing age (incidence rate ratio [IRR] = 1.02 per 1 year of age; 95% CI: 1.01
      1.03; p value = < 0.0001); receiving haemodialysis through a catheter compared to
      arteriovenous fistula (IRR = 2.55; 95% CI: 1.14-4.97; p value = 0.001) and
      diabetes as a cause of renal disease compared to hypertension (IRR = 1.84; 95%
      CI: 1.29-2.63; p value = 0.001). CONCLUSION: Indications for hospitalisation and
      consequences of practices related to hospitalisation for haemodialysis patients
      should be studied in further research to provide a comprehensive evidence-based
      management policy for haemodialysis patients in Saudi Arabia.

PMID- 25383198
TI  - Listening to Mozart K.448 decreases electroencephalography oscillatory power
      associated with an increase in sympathetic tone in adults: a post-intervention
      study.
AB  - OBJECTIVE: Listening to Mozart K.448 has been demonstrated to improve spatial
      task scores, leading to what is known as the Mozart Effect. However, most of
      these reports only describe the phenomena but lack the scientific evidence needed
      to properly investigate the mechanism of Mozart Effect. In this study, we used
      electroencephalography (EEG) and heart rate variability (HRV) to evaluate the
      effects of Mozart K.448 on healthy volunteers to explore Mozart Effect. DESIGN:
      An EEG-based post-intervention analysis. SETTING: Kaohsiung Medical University
      Hospital, Kaohsiung, Taiwan. PARTICIPANTS: Twenty-nine college students were
      enrolled. They received EEG and electrocardiogram examinations simultaneously
      before, during and after listening to the first movement of Mozart K.448. MAIN
      OUTCOME MEASURE: EEG alpha, theta and beta power and HRV were compared in each
      stage. RESULTS: The results showed a significant decrease in alpha, theta and
      beta power when they listened to Mozart K.448. In addition, the average root mean
      square successive difference, the proportion derived by dividing NN50 by the
      total number of NN intervals, standard deviations of NN intervals and standard
      deviations of differences between adjacent NN intervals showed a significant
      decrease, while the high frequency revealed a significant decrease with a
      significantly elevated low-frequency/high-frequency ratio. CONCLUSION: Listening
      to Mozart K.448 significantly decreased EEG alpha, theta and beta power and HRV.
      This study indicates that there is brain cortical function and sympathetic tone
      activation in healthy adults when listening to Mozart K.448, which may play an
      important role in the mechanism of Mozart Effect.

PMID- 25383199
TI  - Using stakeholder perspectives to develop an ePrescribing toolkit for NHS
      Hospitals: a questionnaire study.
AB  - OBJECTIVE: To evaluate how an online toolkit may support ePrescribing deployments
      in National Health Service hospitals, by assessing the type of knowledge-based
      resources currently sought by key stakeholders. DESIGN: Questionnaire-based
      survey of attendees at a national ePrescribing symposium. SETTING: 2013 National
      ePrescribing Symposium in London, UK. PARTICIPANTS: Eighty-four delegates were
      eligible for inclusion in the survey, of whom 70 completed and returned the
      questionnaire. MAIN OUTCOME MEASURES: Estimate of the usefulness and type of
      content to be included in an ePrescribing toolkit. RESULTS: Interest in a toolkit
      designed to support the implementation and use of ePrescribing systems was high
      (n = 64; 91.4%). As could be expected given the current dearth of such a
      resource, few respondents (n = 2; 2.9%) had access or used an ePrescribing
      toolkit at the time of the survey. Anticipated users for the toolkit included
      implementation (n = 62; 88.6%) and information technology (n = 61; 87.1%) teams,
      pharmacists (n = 61; 87.1%), doctors (n = 58; 82.9%) and nurses (n = 56; 80.0%).
      Summary guidance for every stage of the implementation (n = 48; 68.6%), planning
      and monitoring tools (n = 47; 67.1%) and case studies of hospitals' experiences
      (n = 45; 64.3%) were considered the most useful types of content. CONCLUSIONS:
      There is a clear need for reliable and up-to-date knowledge to support
      ePrescribing system deployments and longer term use. The findings highlight how a
      toolkit may become a useful instrument for the management of knowledge in the
      field, not least by allowing the exchange of ideas and shared learning.

PMID- 25383200
TI  - Diagnostic criteria for adverse health effects in the environs of wind turbines.
AB  - In an effort to address climate change, governments have pursued policies that
      seek to reduce greenhouse gases. Alternative energy, including wind power, has
      been proposed by some as the preferred approach. Few would debate the need to
      reduce air pollution, but the means of achieving this reduction is important not
      only for efficiency but also for health protection. The topic of adverse health
      effects in the environs of industrial wind turbines (AHE/IWT) has proven to be
      controversial and can present physicians with challenges regarding the management
      of an exposure to IWT. Rural physicians in particular must be aware of the
      possibility of people presenting to their practices with a variety of sometimes
      confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT
      was published in August 2011. A revised case definition and a model for a study
      to establish a confirmed diagnosis is proposed. 

PMID- 25383201
TI  - Chinese National Guidelines on Diagnosis and Management of Cough: consensus and
      controversy.

PMID- 25383202
TI  - Atopic cough and fungal allergy.
AB  - We have shown that some patients presenting with chronic bronchodilator-resistant
      non-productive cough have a global atopic tendency and cough hypersensitivity
      without nonspecific bronchial hyperresponsiveness, abbreviated as atopic cough
      (AC). The cough can be treated successfully with histamine H1 antagonists and/or
      glucocorticoids. Eosinophilic tracheobronchitis and cough hypersensitivity are
      pathological and physiological characteristics of AC. Fungus-associated chronic
      cough (FACC) is defined as chronic cough associated with basidiomycetous (BM)
      fungi found in induced sputum, and recognition of FACC has provided the
      possibility of using antifungal drugs as new treatment strategies. Bjerkandera
      adusta is a wood decay BM fungus, which has attracted attention because of its
      potential role in enhancing the severity of cough symptoms in FACC patients by
      sensitization to this fungus. Before making a diagnosis of "idiopathic cough" in
      cases of chronic refractory cough, remaining intractable cough-related laryngeal
      sensations, such as "a sensation of mucus in the throat (SMIT)," which is
      correlated with fungal colonization, should be evaluated and treated
      appropriately in each patient. The new findings, i.e., the detection of
      environmental mushroom spores that should not be present in the human airways in
      addition to the good clinical response of patients to antifungal drugs, may lead
      to the development of novel strategies for treatment of chronic cough. 

PMID- 25383203
TI  - Approach to chronic cough: the neuropathic basis for cough hypersensitivity
      syndrome.
AB  - Chronic cough is a common symptom that can be difficult to manage because
      associated causes may remain elusive and treatment of any associated cause may
      not provide relief. Current antitussives have limited efficacy and undesirable
      side-effects. Patients with chronic cough describe sensory symptoms suggestive of
      upper airway and laryngeal neural dysfunction, and report cough triggered by low
      level physical and chemical stimuli supporting the concept of cough reflex
      hypersensitivity. Mechanisms underlying peripheral and central augmentation of
      the afferent cough pathways have been identified. Chronic cough is a neuropathic
      condition that could be secondary to sensory nerve damage caused by inflammatory,
      infective and allergic factors. Recent success in the treatment of chronic cough
      with agents used for treating neuropathic pain such as gabapentin and
      amitryptiline would also support this concept. Research into neuropathic cough
      may lead to the discovery of more effective antitussives. 

PMID- 25383204
TI  - Effect of viral upper respiratory tract infection on cough reflex sensitivity.
AB  - Acute viral upper respiratory tract infection (URI; common cold) is among the
      most common medical conditions affecting man, with cough being a typical feature
      of the associated syndrome. Studies employing capsaicin inhalation challenge to
      measure cough reflex sensitivity have demonstrated a transient tussive
      hyperresponsiveness induced by URI that reverts to normal by 4-8 weeks post
      infection. Mechanisms proposed to explain the induction of cough by URI include a
      number of infection-associated airway effects, such as enhanced release of
      cytokines, neurotransmitters, and leukotrienes; increased neural receptor levels;
      reduced activity of neutral endopeptidases; transient modulation of afferent
      neural activity; mucus hypersecretion; and, possibly, effects on cholinergic
      motor pathways. Recent studies evaluating urge-to-cough (UTC), the sensation of
      irritation preceding the motor act of coughing, have demonstrated that URI
      induces a transient enhancement of UTC analogous to the effect observed on cough
      reflex sensitivity. The recently introduced concept of the Cough Hypersensitivity
      Syndrome may provide an explanation for the commonly observed clinical phenomenon
      of acute viral URI triggering what will develop into chronic, refractory cough in
      a subgroup of patients. 

PMID- 25383205
TI  - Afferent neural pathways mediating cough in animals and humans.
AB  - The airways and lungs are densely innervated by sensory nerves, which subserve
      multiple roles in both the normal physiological control of respiratory functions
      and in pulmonary defense. These sensory nerves are therefore not homogeneous in
      nature, but rather have physiological, molecular and anatomical phenotypes that
      reflect their purpose. All sensory neuron subtypes provide input to the central
      nervous system and drive reflex changes in respiratory and airway functions. But
      less appreciated is that ascending projections from these brainstem inputs to
      higher brain regions can also induce behavioural changes in respiration. In this
      brief review we provide an overview of the current understanding of airway
      sensory pathways, with specific reference to those involved in reflex and
      behavioural cough responses following airways irritation. 

PMID- 25383206
TI  - Shape of concentration-response curves between long-term particulate matter
      exposure and morbidities of chronic bronchitis: a review of epidemiological
      evidence.
AB  - Numerous studies have assessed the concentration-response (C-R) relationships
      between long-term exposure to particulate matter (PM) and mortality from
      cardiopulmonary diseases, but few studies have evaluated the C-R relationships
      between PM exposure and morbidity of chronic respiratory diseases or their
      symptoms, and to date no systematic review has been published on the
      characteristics of the C-R curves between PM exposure and respiratory disease
      morbidity. Screening of all available studies in Medline identified ten studies
      with figures or scatter plots showing the C-R relationships between PM exposure
      and chronic bronchitis or chronic cough/phlegm. The C-R relationships showed
      ballistic 'S' shaped curves, linear in the low to moderate PM range and
      flattening out in the high PM range. Moreover, the shape and level of the C-R
      curves differed markedly between susceptible and nonsusceptible populations. New
      evidence from a prospective cohort study confirmed that the C-R relationship
      between PM reduction and beneficial effects on respiratory health may be due to
      the decreased incidence of respiratory symptoms and increased recovery in
      individuals with symptoms of bronchitis. Additional studies are needed to assess
      the C-R relationships between different PM contents and chronic health
      parameters, especially in geographic areas with high PM pollution and in more
      susceptible populations. Evidence from prospective cohort studies in developing
      countries with areas of high PM pollution may help evaluate the burden of chronic
      respiratory disease attributable to PM pollution and air quality standards. 

PMID- 25383207
TI  - An update on measurement and monitoring of cough: what are the important study
      endpoints?
AB  - Considerable progress has been achieved in the development of tools that assess
      cough. The visual analogue scale (VAS) for cough severity is widely used in
      clinical practice because it's simple and practical. The Leicester cough
      questionnaire (LCQ) and the cough-specific quality of life questionnaire (CQLQ)
      are the most widely used health status questionnaires for adults with chronic
      cough. They are well validated for assessing the impact of cough. Cough can be
      assessed objectively with challenge tests that measure the sensitivity of the
      cough reflex. Cough challenge tests are better used to determine the mechanism of
      action of therapy, rather than efficacy. Cough frequency monitoring, the
      preferred tool to objectively assess cough, is increasingly being used as primary
      end-points in clinical trials. The most widely used cough monitors are the
      Leicester cough monitor (LCM) and VitaloJak. They are ambulatory devices that
      consist of a microphone and recording device. Cough frequency monitors do not
      reflect the intensity or the impact of cough; hence their relationship with
      subjective measures of cough is weak. Cough should therefore be assessed with a
      combination of subjective and objective tools. There is a paucity of studies that
      have investigated the minimal important difference of cough frequency monitors,
      rendering further investigations needed. 

PMID- 25383208
TI  - Developing antitussives the clinician's pipeline-what do we need?
AB  - The evolving concept of cough hypersensitivity, an over activity of the afferent
      sensory nerves in the upper airways, has given new insights into the
      pathophysiology underlying chronic cough. Armed with this new information drug
      development aimed at reducing cough reflex sensitivity to normal has, for the
      first time, led to successful clinical studies. This review outlines the concepts
      underlying the inflammatory processes leading to cough hypersensitivity and
      demonstrates how knowledge of the molecular pharmacology of hypersensitivity
      provides a lead into drug targets. Initial hope that antagonists of TRP receptors
      would reduce clinical cough has been disappointing. Drugs such as theobromine,
      thalidomide and AF 219 which all have activity on afferent sensory nerves have
      shown promise in clinical trials. Large-scale phase three clinical studies are
      required to confirm these exciting findings. 

PMID- 25383210
TI  - Arnold's nerve cough reflex: evidence for chronic cough as a sensory vagal
      neuropathy.
AB  - Arnold's nerve ear-cough reflex is recognised to occur uncommonly in patients
      with chronic cough. In these patients, mechanical stimulation of the external
      auditory meatus can activate the auricular branch of the vagus nerve (Arnold's
      nerve) and evoke reflex cough. This is an example of hypersensitivity of vagal
      afferent nerves, and there is now an increasing recognition that many cases of
      refractory or idiopathic cough may be due to a sensory neuropathy of the vagus
      nerve. We present two cases where the cause of refractory chronic cough was due
      to sensory neuropathy associated with ear-cough reflex hypersensitivity. In both
      cases, the cough as well as the Arnold's nerve reflex hypersensitivity were
      successfully treated with gabapentin, a treatment that has previously been shown
      to be effective in the treatment of cough due to sensory laryngeal neuropathy
      (SLN). 

PMID- 25383211
TI  - Prof. Kian Fan Chung: neuropathic mechanisms of chronic cough and views on air
      pollution.

PMID- 25383209
TI  - Recent additions in the treatment of cough.
AB  - BACKGROUND: Worldwide, cough is regarded as a challenging clinical problem due to
      its frequency and often limited therapeutic options. Chronic cough that remains
      refractory to usual medical treatment causes significant quality of life
      impairment in people with this problem. METHODS: We have examined current
      evidence on recent additions in the treatment of cough, specifically treatment of
      refractory chronic cough with speech pathology and gabapentin. Relevant
      randomised control trials, reviews and case reports were identified through a
      PubMed and SCOPUS search of English-language literature referring to these
      concepts over the last eight years. SUMMARY: Of the one hundred and two articles
      comprising this review the majority investigated the role of the transient
      receptor potential (TRP) receptors TRP Vanilloid 1 (TRPV1) and TRPA1 in cough and
      the potential of TRP antagonists as effective anti-tussives. However, these have
      only been tested in the laboratory and therefore their clinical effectiveness is
      unknown. Behavioural treatments such as speech pathology have gained momentum and
      this was evident in the increasing number of articles investigating its positive
      effect on cough. Investigation on the effectiveness of neuromodulating
      medications in the treatment of cough have been supported primarily through case
      series reports and prospective reviews however; their use (particularly
      gabapentin) has been significantly advanced through recently conducted randomised
      controlled trials. CONCLUSIONS: Recent additions in the treatment of chronic
      cough have been significant as they consider cough to have a unifying diagnosis
      of cough hypersensitivity with or without the presence of a neuropathic basis.
      Primarily, effective treatments for chronic cough target these areas and include
      behavioural treatment such as speech pathology and pharmaceutical treatment with
      neuromodulating medications such as gabapentin.

PMID- 25383212
TI  - Prof. Kefang Lai: the diagnosis and treatment of cough in China.

PMID- 25383213
TI  - Prof. Alyn Morice: the etiology, diagnosis and treatment of cough.

PMID- 25383214
TI  - Prof. Akio Niimi: the clinical identification of cough variant asthma.

PMID- 25383215
TI  - Differential Susceptibility of Bacteria to Mouse Paneth Cell alpha-Defensins
      under Anaerobic Conditions.
AB  - Small intestinal Paneth cells secrete alpha-defensin peptides, termed cryptdins
      (Crps) in mice, into the intestinal lumen, where they confer immunity to oral
      infections and define the composition of the ileal microbiota. In these studies,
      facultative bacteria maintained under aerobic or anaerobic conditions displayed
      differential sensitivities to mouse alpha-defensins under in vitro assay
      conditions. Regardless of oxygenation, Crps 2 and 3 had robust and similar
      bactericidal activities against S. Typhimurium and S. flexneri, but Crp4 activity
      against S. flexneri was attenuated in the absence of oxygen. Anaerobic bacteria
      varied in their susceptibility to Crps 2-4, with Crp4 showing less activity than
      Crps 2 and 3 against Enterococcus faecalis, and Bacteroides fragilis in anaerobic
      assays, but Fusobacterium necrophorum was killed only by Crp4 and not by Crps 2
      and 3. The influence of anaerobiosis in modulating Crp bactericidal activities in
      vitro suggests that alpha-defensin effects on the enteric microbiota may be
      subject to regulation by local oxygen tension.

PMID- 25383217
TI  - A novel inhibitor of Mammalian triosephosphate isomerase found by an in silico
      approach.
AB  - Triosephosphate isomerase (TIM) is an essential, highly conserved component of
      glycolysis. Tumors are often dependent on glycolysis for energy and metabolite
      production (the Warburg effect). Glycolysis inhibitors thus show promise as
      cancer treatments. TIM inhibition, unlike inhibition of other glycolysis enzymes,
      also produces toxic methylglyoxal targeted to regions of high glycolysis, an
      effect that might also be therapeutically useful. Thus TIM is an attractive drug
      target. A total of 338,562 lead-like molecules were analyzed computationally to
      find TIM inhibitors by an efficient "double screen" approach. The first fragment
      sized compounds were studied using structure-based virtual screening to identify
      binding motifs for mammalian TIM. Subsequently, larger compounds, filtered to
      meet the binding criteria developed in the first analysis, were ranked using a
      second round of structure-based virtual screening. A compound was found that
      inhibited mammalian TIM in vitro in the micromolar range. Docking and molecular
      dynamics (MD) suggested that the inhibitor made hydrogen bond contacts with TIM
      catalytic residues. In addition, hydrophobic contacts were made throughout the
      binding site. All predicted inhibitor-TIM interactions involved TIM residues that
      were highly conserved. The discovered compound may provide a scaffold for
      elaboration of other inhibitors. 

PMID- 25383216
TI  - Significance and biological importance of pyrimidine in the microbial world.
AB  - Microbes are unique creatures that adapt to varying lifestyles and environment
      resistance in extreme or adverse conditions. The genetic architecture of microbe
      may bear a significant signature not only in the sequences position, but also in
      the lifestyle to which it is adapted. It becomes a challenge for the society to
      find new chemical entities which can treat microbial infections. The present
      review aims to focus on account of important chemical moiety, that is, pyrimidine
      and its various derivatives as antimicrobial agents. In the current studies we
      represent more than 200 pyrimidines as antimicrobial agents with different mono-,
      di-, tri-, and tetrasubstituted classes along with in vitro antimicrobial
      activities of pyrimidines derivatives which can facilitate the development of
      more potent and effective antimicrobial agents. 

PMID- 25383218
TI  - Experimental Design-Based Response Surface Methodology Optimization for Synthesis
      of beta-Mercapto Carbonyl Derivatives as Antimycobacterial Drugs Catalyzed by
      Calcium Pyrophosphate.
AB  - A simple protocol for the efficient preparation of beta-mercapto carbonyl
      derivatives as antimycobacterial drugs has been achieved via Thia-Michael
      reaction between chalcones derivatives and thiols in the presence of calcium
      pyrophosphate as a heterogeneous catalyst under mild reaction conditions. The
      central composite design was used to design an experimental program to provide
      data to model the effects of various factors on reaction yield (Y). The variables
      chosen were catalyst weight (X 1), reaction time (X 2), and solvent volume (X 3).
      The mathematical relationship of reaction yield on the three significant
      independent variables can be approximated by a nonlinear polynomial model.
      Predicted values were found to be in good agreement with experimental values. The
      optimum reaction conditions for reaction model (chalcone and thiophenol) obtained
      by response surface were applied to other substrates. This procedure provides
      several advantages such as high yield, clean product formation, and short
      reaction time. 

PMID- 25383219
TI  - Target Based Designing of Anthracenone Derivatives as Tubulin Polymerization
      Inhibiting Agents: 3D QSAR and Docking Approach.
AB  - Novel anthracenone derivatives were designed through in silico studies including
      3D QSAR, pharmacophore mapping, and molecular docking approaches. Tubulin protein
      was explored for the residues imperative for activity by analyzing the binding
      pattern of colchicine and selected compounds of anthracenone derivatives in the
      active domain. The docking methodology applied in the study was first validated
      by comparative evaluation of the predicted and experimental inhibitory activity.
      Furthermore, the essential features responsible for the activity were established
      by carrying out pharmacophore mapping studies. 3D QSAR studies were carried out
      for a series of 1,5- and 1,8-disubstituted10-benzylidene-10H-anthracen-9-ones and
      10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-one derivatives for their
      antiproliferation activity. Based on the pattern recognition studies obtained
      from QSAR results, ten novel compounds were designed and docked in the active
      domain of tubulin protein. One of the novel designed compounds "N1" exhibited
      binding energy -9.69 kcal/mol and predicted Ki 78.32 nM which was found to be
      better than colchicine. 

PMID- 25383220
TI  - Synthesis and biological evaluation of aminonaphthols incorporated indole
      derivatives.
AB  - An efficient one pot condensation of naphthols (1), 2,5-disubstituted indole-3
      carboxaldehydes (2), and secondary amines (3) has been achieved using
      dichloromethane as a solvent, stirring at room temperature. Some of the new
      [(disubstituted amino)(5-substituted 2-phenyl-1H-indol-3-yl)methyl]naphthalene
      ols (4) derivatives were prepared in good yields. The significant features of
      this method are simple work-up procedure, inexpensive nontoxic solvent, shorter
      reaction times, and excellent product yields. The structures of newly synthesized
      compounds (4a-r) are confirmed by their elemental analysis, FTIR, (1)H and (13)C
      NMR, and mass spectral data. These compounds were screened for their in vitro
      antioxidant, antimicrobial, antitubercular, and anticancer activities. Among the
      synthesized compounds (4a-r), the compound 4e exhibited highest activity for
      radical scavenging and ferric ions reducing antioxidant power activities;
      compounds 4b, 4h, and 4k showed good metal chelating activity. Compounds 4n and
      4q showed excellent antimicrobial activities with MIC value 08 ug/mL against
      tested strains. Compounds 4h, 4k, 4n, and 4q exhibited promising antitubercular
      activity with MIC value 12.5 ug/mL. Compounds 4k and 4q exhibited 100% cell lysis
      at concentration 10 ug/mL against MDA-MB-231 (human adenocarcinoma mammary gland)
      cell lines. 

PMID- 25383221
TI  - Docking studies and biological activity of fosinopril analogs.
AB  - The purpose of the present study was to determine the angiotensin-I converting
      enzyme inhibitory activity of few novel Fosinopril derivatives which were
      predicted to possess better ACE inhibitory activity and lesser side effects than
      the existing drug molecule. In vitro study was carried out to determine ACE
      inhibitory activity of six different Fosinopril analogs by spectrophotometric
      assay procedure. Analog A2 showed the highest activity compared to other analogs
      and as well as Fosinopril itself. Docking studies of the compounds were done with
      the help of VLife MDS 3.0 software using GRIP batch docking method to find out
      which derivative had a better docking with ACE. The compounds which showed the
      highest negative score in docking have also exhibited good ACE inhibitory
      activity. 

PMID- 25383222
TI  - Abrus precatorius Leaves: Antioxidant Activity in Food and Biological Systems,
      pH, and Temperature Stability.
AB  - Natural antioxidants present in foods and other biological materials have
      attracted considerable interest because of their presumed safety and potential
      nutritional and therapeutic effects. Antioxidant constituents of plant materials
      act as radical scavengers and convert the radicals to less reactive species.
      Abrus precatorius (AP) was analyzed for its proximate and phytochemical
      composition. The leaves were extracted with methanol (ME) and analyzed for
      antioxidant activity by radical scavenging method, reducing power, ferric
      reducing capacity, and in vitro inhibition of Fenton's reagent-induced oxidation
      in oil emulsion and microsomes. In addition, the effect of temperature (100
      degrees C, 15, and 30 min) and pH (4.5, 7, and 9) C on the antioxidant activity
      of ME was investigated. The leaves were rich in total polyphenols, flavonoids,
      beta-carotene, glutathione, alpha-tocopherol, and ascorbic acid. The ME exhibited
      varying degree of antioxidant activity in a dose-dependent manner. The AP
      exhibited more inhibition of oxidation in microsomes (73%) than compared to oil
      emulsion (21%). Heat treatment resulted in an increase of radical scavenging
      activity of extract (28% to 43%). At pH 4.5 the extract exhibited more
      antioxidant activity and stability compared to pH 7 and 9. Data indicates that
      potential exists for the utilization of Abrus precatorius as a natural
      antioxidant. 

PMID- 25383224
TI  - Nitro Derivatives of Naturally Occurring beta -Asarone and Their Anticancer
      Activity.
AB  - beta-Asarone (2, 4, 5-trimethoxy-(Z)-1-propenylbenzene) was obtained from Acorus
      calamus. Nitration of beta-asarone with AgNO2/I2 in ether yielded 1-(2, 4, 5
      trimethoxy phenyl)-2-nitropropene (1) but with NaNO2/I2 in ethylene glycol
      obtained 1-(2, 4, 5-trimethoxy phenyl)-1-nitropropene (2). Compound 2 was
      prepared for the first time and characterized using IR, (1)H-NMR, (13)C-NMR, and
      GC-MS spectra and it was converted into 1-(2, 4, 5-trimethoxy) phenyl-1-propanone
      (3) using modified Nef reaction. Based on 1D NOESY experiments, compounds 1 and 2
      have been assigned E configuration. Compounds 1 and 2 were subjected to cytotoxic
      activity using five human cancer cell lines, namely, MCF-7, SW-982, HeLa, PC-3,
      and IMR-32 by MTT assay. Except in breast cancer line (MCF-7) compound 2
      exhibited five- to tenfold increase in activity compared to beta-asarone and
      twofold increase over compound 1. 

PMID- 25383223
TI  - Therapeutic potential of hydrazones as anti-inflammatory agents.
AB  - Hydrazones are a special class of organic compounds in the Schiff base family.
      Hydrazones constitute a versatile compound of organic class having basic
      structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and
      nitrogen, are mainly responsible for the physical and chemical properties of the
      hydrazones and, due to the reactivity toward electrophiles and nucleophiles,
      hydrazones are used for the synthesis of organic compound such as heterocyclic
      compounds with a variety of biological activities. Hydrazones and their
      derivatives are known to exhibit a wide range of interesting biological
      activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic,
      antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic,
      antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular,
      trypanocidal, anti-HIV, and so forth. The present review summarizes the
      efficiency of hydrazones as potent anti-inflammatory agents. 

PMID- 25383225
TI  - Clicked cinnamic/caffeic esters and amides as radical scavengers and 5
      lipoxygenase inhibitors.
AB  - 5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of
      arachidonic acid to leukotrienes, a class of lipid mediators implicated in
      inflammatory disorders. In this paper, we describe the design, synthesis, and
      preliminary activity studies of novel clicked caffeic esters and amides as
      radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead,
      cinnamic esters 8a-h and amides 9a-h as well as caffeic esters 15a-h and amides
      16a-h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the
      appropriate azide precursors and terminal alkynes. All caffeic analogs are proved
      to be good radical scavengers (IC50: 10-20 MUM). Esters 15g and 15f possessed
      excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the
      known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized
      esters possess activities rivaling Zileuton in stimulated human polymorphonuclear
      leukocytes. 

PMID- 25383226
TI  - Sentinel Node Biopsy Alone versus Completion Axillary Node Dissection in Node
      Positive Breast Cancer: Systematic Review and Meta-Analysis.
AB  - Introduction. There has been recent interest in validity of completion axillary
      node dissection after a positive sentinel node. This systematic review aims to
      ascertain if sentinel lymph node dissection alone was noninferior to axillary
      lymph node dissection for breast cancer patients who have a positive sentinel
      node. Method. A systematic review of the electronic databases Embase, MEDLINE,
      and Cochrane Register of Controlled Trials was carried out. Only randomised
      trials that had patients with positive sentinel node as the study sample were
      included in the meta-analysis using the reported hazard ratios with a fixed
      effect model. Results. Three randomised controlled trials and five retrospective
      studies were identified. The pooled effect for overall survival was HR 0.94, 95%
      CI [0.79, 1.19], and for disease free survival was HR 0.83, 95% CI [0.60, 1.14].
      The reported rates for locoregional recurrence were similar in both groups. The
      surgical morbidity was found to be significantly more in patients who had
      underwent axillary dissection. Conclusion. Amongst patients with micrometastasis
      in the sentinel node, no further axillary dissection is necessary. For patients
      with macrometastasis in the sentinel node, it is reasonable to consider omitting
      axillary dissection to avoid the morbidity of the procedure. 

PMID- 25383227
TI  - Spontaneous Bacterial Peritonitis Caused by Listeria monocytogenes Associated
      with Ascitic Fluid Lymphocytosis: A Case Report and Review of Current Empiric
      Therapy.
AB  - Spontaneous bacterial peritonitis (SBP) is a potentially deadly complication of
      ascites. We describe a case of SBP caused by Listeria monocytogenes in a patient
      with alcoholic cirrhosis. This was associated with the unusual finding of ascitic
      fluid lymphocytosis, which previously had only been associated with tuberculoid
      or malignant ascites. Given increasing rates of cefotaxime-resistant SBP
      alongside the possibility of Listeriosis, the use of cefotaxime as first-line
      therapy in SBP should be reevaluated. 

PMID- 25383228
TI  - Low-dose tolvaptan for the treatment of dilutional hyponatremia in cirrhosis: a
      case report and literature review.
AB  - Dilutional hyponatremia is common in decompensated cirrhosis and can be
      successfully treated by tolvaptan, a vasopressin V2-receptor antagonist. Data
      were lacking regarding the effects of tolvaptan on cirrhotic patients with a
      Child-Pugh score of >10 and a serum sodium concentration of <120 mmol/L. We
      report a case of forties man with a 20-year history of chronic hepatitis B
      presenting with yellow urine and skin. Laboratory tests demonstrated prolonged
      prothrombin time, markedly elevated total bilirubin, severe hyponatremia, and a
      Child-Pugh score of >10. The patient was diagnosed with dilutional hyponatremia
      and was treated with recommended dosage tolvaptan at first. The serum
      concentration of sodium recover but the patient felt obviously thirsty. As the
      dosage of tolvaptan was decreased accordingly from 15 mg to 5 mg, the patient
      still maintained the ideal concentration of serum sodium. This case emphasizes
      that cirrhotic patient with higher Child-Pugh scores and serum sodium
      concentration of <120 mmol/L can be treated with lower dose of tolvaptan. 

PMID- 25383229
TI  - Persistent Lymphadenopathy due to IgG4-Related Disease.
AB  - A 28-year-old healthy female presented to her primary care physician with
      lymphadenopathy, fatigue, malaise, and night sweats. Symptoms persisted despite
      conservative treatment and eventually the patient underwent multiple lymph node
      resections and a bone marrow biopsy before a diagnosis of IgG4-related disease
      (IgG4-RD) was made. IgG4-RD is a relatively new disorder first
      histopathologically recognized within the last decade. As the disease can affect
      a single organ or multiple organs, symptoms can vary greatly among patients. With
      symptoms ranging from mild, such as lower extremity edema, to severe, such as
      spinal cord compression, IgG4-RD must be considered in appropriate patients.
      Diagnostic criteria have been proposed based on organ involvement, serum IgG4
      levels, and histopathological criteria. Diagnosis can be difficult to make with
      many studies suggesting different values for diagnostic criteria, such as the
      level of tissue IgG4+/IgG+ cell ratio to delineate IgG4-RD. Treatment consists of
      high dose glucocorticoids as a first line therapy with some patients choosing
      instead to simply undergo observation. This case illustrates the difficulty in
      diagnosis and the need for increased awareness among medical professionals. 

PMID- 25383230
TI  - Intravenous Immunoglobulin and Mycophenolate Mofetil for Long-Standing Sensory
      Neuronopathy in Sjogren's Syndrome.
AB  - Sensory neuronopathy is described in association with the Sjogren's syndrome
      (SS). We studied a 55-year-old woman with a 4-year history of progressive
      asymmetric numbness, distal tingling, and burning sensation in upper and lower
      limbs. In a few months, she developed ataxia with increased hypoanaesthesia.
      Electrodiagnostic tests revealed undetectable distal and proximal sensory nerve
      action potential in upper and lower limbs. Cervical spine magnetic resonance
      showed a signal hyperintensity of posterior columns. Previous treatment with high
      dose glucocorticoids and azathioprine was ineffective. A combined treatment with
      intravenous immunoglobulin and mycophenolate mofetil was followed by a
      progressive and persistent improvement. This case documented the efficacy and the
      safety of the coadministration of intravenous immunoglobulin and mycophenolate
      mofetil in sensory neuronopathy associated with SS refractory to conventional
      immunosuppressive therapy. 

PMID- 25383231
TI  - Time Course of the Changes in Novel Trioxane Antimalarial 99/411 Pharmacokinetics
      upon Antiepileptic Drugs Co-Administration in SD Rats.
AB  - Objective. The study aimed to evaluate the influences of coadministration of
      antiepileptic drugs (AEDs) on an antimalarial candidate 99/411 pharmacokinetic
      (PK) profile. Method. For this, single oral dose PK drug interaction studies were
      conducted between 99/411 and FDA approved AEDs, namely, Phenytoin (PHT),
      Carbamazepine (CBZ), and Gabapentin (GB) in both male and female SD rats, to
      assess the coadministered and intersexual influences on 99/411 PK profile.
      Results. Studies revealed that there were no significant alterations in the PK
      profile of 99/411 upon PHT and CBZ coadministration in both male and female rats,
      while systemic exposure of 99/411 was significantly increased by about 80% in
      female rats upon GB coadministration. In terms of AUC, there was an increase from
      2471 +/- 586 to 4560 +/- 1396 ng.h/mL. Overall, it was concluded that
      simultaneous administration of AEDs with 99/411 excludes the requirements for
      dose adjustment, additional therapeutic monitoring, contraindication to
      concomitant use, and/or other measures to mitigate risk, except for GB
      coadministration in females. These findings are further helpful to predict such
      interactions in humans, when potentially applied through proper allometric
      scaling to extrapolate the data. 

PMID- 25383233
TI  - Biology by the numbers on the Hawaiian Islands.

PMID- 25383232
TI  - Contrasting Effects of the Neuropeptides Substance P, Somatostatin, and
      Neuropeptide Y on the Methamphetamine-Induced Production of Striatal Nitric Oxide
      in Mice.
AB  - Several laboratories have shown that methamphetamine (METH) neurotoxicity is
      associated with increases of nitric oxide (NO) production in striatal tissue and
      blockade of NO production protects from METH. Because substance P modulates NO
      production, we tested the hypothesis that intrinsic striatal neuropeptides such
      as somatostatin and neuropeptide Y (NPY) modulate striatal NO production in the
      presence of METH. To that end, METH (30 mg/kg, IP) was injected into adult male
      mice alone or in combination with pharmacological agonists or antagonists of the
      neurokinin-1 (substance P), somatostatin or NPY receptors and 3-nitrotyrosine (an
      indirect index of NO production) was assessed utilizing HPLC or a histological
      method. Pre-treatment with the systemic neurokinin-1 receptor antagonist WIN
      51,708 significantly attenuated the METH-induced production of striatal 3-NT
      measured at two hours post-METH. Conversely, intrastriatal injection of NPY1 or 2
      receptor agonists inhibited the METH-induced production of striatal 3-NT.
      Similarly, intrastriatal infusion of the somatostatin receptor agonist octreotide
      attenuated the METH-induced striatal production of 3-NT. Taken together, our
      results suggest the hypothesis that the neuropeptide substance P is pro-damage
      while the neuropeptides somatostatin and NPY are anti-damage in the presence of
      METH by targeting the production of NO.

PMID- 25383234
TI  - A Multi-Function Force Sensing Instrument for Variable Admittance Robot Control
      in Retinal Microsurgery.
AB  - Robotic systems have the potential to assist vitreoretinal surgeons in extremely
      difficult surgical tasks inside the human eye. In addition to reducing hand
      tremor and improving tool positioning, a robotic assistant can provide assistive
      motion guidance using virtual fixtures, and incorporate real-time feedback from
      intraocular force sensing ophthalmic instruments to present tissue manipulation
      forces, that are otherwise physically imperceptible to the surgeon. This paper
      presents the design of an FBG-based, multi-function instrument that is capable of
      measuring mN-level forces at the instrument tip located inside the eye, and also
      the sclera contact location on the instrument shaft and the corresponding contact
      force. The given information is used to augment cooperatively controlled robot
      behavior with variable admittance control. This effectively creates an adaptive
      remote center-of-motion (RCM) constraint to minimize eye motion, but also allows
      the translation of the RCM location if the instrument is not near the retina. In
      addition, it provides force scaling for sclera force feedback. The calibration
      and validation of the multi-function force sensing instrument are presented,
      along with demonstration and performance assessment of the variable admittance
      robot control on an eye phantom.

PMID- 25383235
TI  - Differential Expression of miR-130a in Postmortem Prefrontal Cortex of Subjects
      with Alcohol Use Disorders.
AB  - BACKGROUND: Emerging evidence suggests that neuroadaptations to alcohol may
      result from chronic alcohol consumption-induced expression changes of microRNAs
      (miRNAs) and their target genes. Studies with animal or cell culture models have
      demonstrated that ethanol exposure leads to miRNA expression alterations.
      However, there is limited information on miRNA expression in the brains of
      subjects with alcohol use disorders (AUDs). The present study aimed to analyze
      expression changes of miRNAs and their target genes in postmortem prefrontal
      cortex (PFC) of AUD subjects. METHODS: Genome-wide miRNA and mRNA expression was
      examined in postmortem PFC of 23 European Australia AUD cases and 23 matched
      controls using the Illumina HumanHT-12 v4 Expression BeadChip array, which
      targets 43,270 coding transcripts and 3,961 non-coding transcripts (including 574
      miRNA transcripts). Multiple linear regression analysis and permutation test were
      performed to identify differentially expressed miRNAs and their target mRNAs.
      Target gene prediction, Gene Set Enrichment Analysis (GESA), and DAVID functional
      annotation clustering analysis were applied to identify AUD-associated gene sets
      and biological modules. RESULTS: Two miRNAs and 787 coding genes were
      differentially expressed in the PFC of AUD cases [miR-130a (downregulated):
      Ppermutation=0.023, miR-604 (upregulated): Ppermutation=0.019, coding genes:
      1.6*10-5<=Ppermutation<=0.05; but all P values did not survive multiple-testing
      correction]. GESA showed that the 202 predicted target genes of miR-130a were
      highly enriched in differentially expressed genes (Pnominal<0.001), but not the
      116 predicted target genes of miR-604 (Pnominal=0.404). DAVID functional
      clustering further revealed that the hub target genes (e.g., ITPR2 and ATP1A2) of
      miRNA130a were mainly responsible for regulating ion channel function.
      CONCLUSION: This study provides evidence that downregulation of miR-130a may lead
      to altered expression of a number of genes in the PFC of AUD subjects. Further
      studies are warranted to confirm these findings in replication samples and other
      reward-related brain regions.

PMID- 25383236
TI  - Validation of Self-Reported Measures in Health Disparities Research.
AB  - Validation of self-reported measures can be achieved effectively and accurately
      when data collection involves objective measures that can be clinically
      validated. On the other hand, validation of self-reported social constructs,
      often used in health disparities research is a much harder task to achieve,
      particularly when the outcome is hard to quantify (e.g. racism, discrimination
      and segregation experience). We discuss validation and the challenges faced, when
      using current approaches in health disparities research.

PMID- 25383237
TI  - Statistical Approaches to Assess the Effects of Disease on Neurocognitive
      Function Over Time.
AB  - INTRODUCTION: Assessment of the effects of disease on neurocognitive outcomes in
      children over time presents several challenges. These challenges are particularly
      pronounced when conducting studies in low-income countries, where standardization
      and validation is required for tests developed originally in high-income
      countries. We present a statistical methodology to assess multiple neurocognitive
      outcomes over time. We address the standardization and adjustment for age in
      neurocognitive testing, present a statistical methodology for development of a
      global neurocognitive score, and assess changes in individual and global
      neurocognitive scores over time in a cohort of children with cerebral malaria.
      METHODS: Ugandan children with cerebral malaria (CM, N = 44), uncomplicated
      malaria (UM, N = 54) and community controls (N = 89) were assessed by cognitive
      tests of working memory, executive attention and tactile learning at 0, 3, 6 and
      24 months after recruitment. Tests were previously developed and validated for
      the local area. Test scores were adjusted for age, and a global score was
      developed based on the controls that combined the assessments of impairment in
      each neurocognitive domain. Global normalized Z-scores were computed for each of
      the three study groups. Model-based tests compare the Z-scores between groups.
      RESULTS: We found that continuous Z-scores gave more powerful conclusions than
      previous analyses of the dataset. For example, at all four time points, children
      with CM had significantly lower global Z-scores than controls and children with
      UM. Our methods also provide more detailed descriptions of longitudinal trends.
      For example, the Z-scores of children with CM improved from initial testing to 3
      months, but remained at approximately the same level below those of controls or
      children with UM from 3 to 24 months. Our methods for combining scores are more
      powerful than tests of individual cognitive domains, as testing of the individual
      domains revealed differences at only some but not all time points.

PMID- 25383238
TI  - Recent Research on Febrile Seizures: A Review.
AB  - Febrile seizures are common and mostly benign. They are the most common cause of
      seizures in children less than five years of age. There are two categories of
      febrile seizures, simple and complex. Both the International League against
      Epilepsy and the National Institute of Health has published definitions on the
      classification of febrile seizures. Simple febrile seizures are mostly benign,
      but a prolonged (complex) febrile seizure can have long term consequences. Most
      children who have a febrile seizure have normal health and development after the
      event, but there is recent evidence that suggests a small subset of children that
      present with seizures and fever may have recurrent seizure or develop epilepsy.
      This review will give an overview of the definition of febrile seizures,
      epidemiology, evaluation, treatment, outcomes and recent research.

PMID- 25383240
TI  - A Perspective on the Potential of Human iPS Cell-Based Therapies for Muscular
      Dystrophies: Advancements so far and Hurdles to Overcome.

PMID- 25383239
TI  - Engineered Hematopoietic Stem Cells as Therapeutics for Hemophilia A.

PMID- 25383241
TI  - Increased Apoptosis in Chorionic Trophoblasts of Human Fetal Membranes with Labor
      at Term.
AB  - OBJECTIVE: To determine the association of apoptosis in the layers of human fetal
      membranes with labor at term. STUDY DESIGN: Human fetal membranes were collected
      from elective cesarean sections (n = 8) and spontaneous vaginal deliveries (n =
      8) at term. The extent of apoptosis within the layers of fetal membranes was
      determined using terminal deoxynucleotidyl transferase deoxy-UTP-nick end
      labeling (TUNEL) immunohistochemical assay and western blots. For TUNEL assays, 5
      MUm sections of formalin fixed membranes were used and the apoptotic index
      (number of apoptotic nuclei per total nuclei *100) was determined in 5
      independent microscopic fields. For Western blotting, proteins isolated from the
      amnion and choriodecidua layers were blotted against pro-apoptotic active caspase
      3 and anti-apoptotic and Bcl-2. Data were expressed as the means +/- SD and
      Student's t-test was used for statistical analysis. RESULTS: There was no
      statistical difference in maternal age, gestational age, gravidity, parity, race,
      and smoking between patients who delivered at term via either elective cesarean
      or vaginally. Apoptotic index in chorionic trophoblasts of membranes obtained
      after vaginal delivery was higher than those obtained from elective cesarean
      (11.57 +/- 4.98 % and 4.05 +/- 2.4 % respectively, p = 0.012). The choriodecidua
      layers after vaginal deliveries had higher expression of the pro-apoptotic active
      caspase-3 and less expression of the anti-apoptotic BcL-2 than those obtained
      from elective cesarean sections. CONCLUSIONS: Labor at term is associated with
      increased apoptosis in chorionic trophoblast cells of human fetal membranes. The
      cause-effect relation between apoptosis in fetal membranes and labor warrants
      further investigations.

PMID- 25383242
TI  - Insurance coverage & Whither Thou Goest for health information in 2012.
AB  - OBJECTIVE: Examine use of the Internet (eHealth) and mobile health (mHealth)
      technologies by privately insured, publicly insured (Medicare/Medicaid), or
      uninsured U.S. adults in 2012. DATA SOURCE: Pew Charitable Trust telephone
      interviews of a nationally representative, random sample of 3,014 adult U.S.
      residents, age 18+. METHODS: Estimate health information seeking behavior overall
      and by segment (i.e., insurance type), then, adjust estimates for individual
      traits, clinical need, and technology access using logistic regression. RESULTS:
      Most respondents prefer offline to online (Internet) health information sources;
      over half across all segments use the Internet. More respondents communicate with
      providers offline compared with online. Most self-reported Internet users use
      online tools for health information, with privately insured respondents more
      likely to use new technologies. Unadjusted use rates differ across segments.
      Medicaid beneficiaries are more likely than the privately insured to share health
      information online, and Medicare beneficiaries are more likely than the privately
      insured to text with health professionals. After adjustment, these differences
      were minimal (e.g., Medicare beneficiaries had odds similar to the privately
      insured of online physician consultations), or the direction of the association
      reversed (e.g., Medicaid beneficiaries had greater odds than the privately
      insured of online physician consultations versus lower odds before adjustment).
      DISCUSSION: Few adults report eHealth or mHealth use in 2012. Use levels appear
      unevenly distributed across insurance types, which could be mostly attributed to
      differences in individual traits and/or need. As out-of-pocket costs of medical
      care increases, consumers may increasingly turn to these generally free
      electronic health tools.

PMID- 25383244
TI  - Trunk and hip electromyographic activity during single leg squat exercises do sex
      differences exist?
AB  - PURPOSE/BACKGROUND: Researchers have identified sex-differences in lower
      extremity muscle activation during functional activities that involve landing and
      cutting maneuvers. However, less research has been conducted to determine if
      muscle activation differences occur during rehabilitation exercises. The purpose
      of this investigation was to determine if sex-differences exist for activation
      amplitudes of the trunk and hip muscles during four single leg squat (SLS)
      exercises. METHODS: Eighteen males and 16 females participated. Surface
      electromyography (EMG) was used to determine muscle activity of the abdominal
      obliques (AO), lumbar extensors (LE), gluteus maximus (GMX), and gluteus medius
      (GM) during four SLS exercises. Data were expressed as a percentage of a maximum
      voluntary isometric contraction (% MVIC). A 2 X 4 mixed-model analysis of
      variance with repeated measures was used to determine the interaction between sex
      and exercise on each muscle's activity. RESULTS: No interaction effect existed
      between sex and exercise. A main effect for sex existed for the GM and LE. On
      average, females generated 39% greater GM (27.6 +/- 10.4 % MVIC versus 19.8 +/-
      10.5 % MVIC) and 40% greater LE (8.0 +/- 2.8 % MVIC versus 5.7 +/- 2.8 % MVIC)
      activity than males. All subjects, regardless of sex, demonstrated similar GMX
      and AO activity. Overall EMG values ranged from 11.0 % MVIC to 14.7 % MVIC for
      the GMX and 5.7 % MVIC to 8.8 % MVIC for the AO. CONCLUSIONS: None of the
      subjects generated sufficient EMG activity for strength gains. Females generated
      a moderate level of GM activity appropriate for neuromuscular re
      education/endurance. Males generated a low level of GM activity that may not
      necessarily be sufficient to improve GM function. Subjects exhibited low levels
      of EMG activity for the other muscles. These findings suggest that clinicians
      modify and/or prescribe different exercises than those studied herein for the
      purpose of improving GM, GMX, AO, and LE function. LEVEL OF EVIDENCE: 3b.

PMID- 25383245
TI  - Rehabilitation following hip arthroscopy: an evolving process.
AB  - The utilization of hip arthroscopy to treat non-arthritic pain in athletes
      continues to grow in popularity. Though numerous protocols have been described in
      the literature, there is no current evidence-based consensus regarding the
      postoperative management of patients undergoing hip arthroscopy. Intraoperative
      findings determine the specific surgical procedure and subsequently play a role
      in postoperative rehabilitation. Current protocols are primarily based on tissue
      healing properties, patient tolerance, and clinician experience. General
      recommendations regarding range-of-motion initiation, weight bearing progression,
      and strength activities exist. Though relatively uncommon, postoperative
      complications have been described. Clinicians should be aware of factors, both
      surgical and rehabilitation-related, that may affect a patient's postoperative
      progression. In order to assess patients' postoperative improvement, clinicians
      must utilize outcome measures that effectively assess the functional status level
      of active individuals following hip arthroscopy. The development of criteria
      based programs may improve the consistency of rehabilitation and potentially aid
      in providing patients a safe, efficient return to athletics. 

PMID- 25383243
TI  - Clinical examination and physical assessment of hip joint-related pain in
      athletes.
AB  - Evidence-based clinical examination and assessment of the athlete with hip joint
      related pain is complex. It requires a systematic approach to properly
      differentially diagnose competing potential causes of athletic pain generation.
      An approach with an initial broad focus (and hence use of highly sensitive
      tests/measures) that then is followed by utilizing more specific tests/measures
      to pare down this imprecise differential diagnosis list is suggested. Physical
      assessment measures are then suggested to discern impairments, activity and
      participation restrictions for athletes with hip-join related pain, hence guiding
      the proper treatment approach. LEVEL OF EVIDENCE: 5.

PMID- 25383246
TI  - Athletic pubalgia and associated rehabilitation.
AB  - BACKGROUND: Evaluation and treatment of groin pain in athletes is challenging.
      The anatomy is complex, and multiple pathologies often coexist. Different
      pathologies may cause similar symptoms, and many systems can refer pain to the
      groin. Many athletes with groin pain have tried prolonged rest and various
      treatment regimens, and received differing opinions as to the cause of their
      pain. The rehabilitation specialist is often given a non-specific referral of
      "groin pain" or "sports hernia." The cause of pain could be as simple as the
      effects of an adductor strain, or as complex as athletic pubalgia or inguinal
      disruption. The term "sports hernia" is starting to be replaced with more
      specific terms that better describe the injury. Inguinal disruption is used to
      describe the syndromes related to the injury of the inguinal canal soft tissue
      environs ultimately causing the pain syndrome. The term athletic pubalgia is used
      to describe the disruption and/or separation of the more medial common
      aponeurosis from the pubis, usually with some degree of adductor tendon
      pathology. TREATMENT: Both non-operative and post-operative treatment options
      share the goal of returning the athlete back to pain free activity. There is
      little research available to reference for rehabilitation guidelines and creation
      of a plan of care. Although each surgeon has their own specific set of post
      operative guidelines, some common concepts are consistent among most surgeons.
      Effective rehabilitation of the high level athlete to pain free return to play
      requires addressing the differences in the biomechanics of the dysfunction when
      comparing athletic pubalgia and inguinal disruption. CONCLUSION: Proper
      evaluation and diagnostic skills for identifying and specifying the difference
      between athletic pubalgia and inguinal disruption allows for an excellent and
      efficient rehabilitative plan of care. Progression through the rehabilitative
      stages whether non-operative or post-operative allows for a focused
      rehabilitative program. As more information is obtained through MRI imaging and
      the diagnosis and treatment of inguinal disruption and athletic pubalgia becomes
      increasingly frequent, more research is warranted in this field to better improve
      the evidence based practice and rehabilitation of patients. LEVELS OF EVIDENCE:
      5.

PMID- 25383247
TI  - Rehabilitation of soft tissue injuries of the hip and pelvis.
AB  - Soft tissue injuries of the hip and pelvis are common among athletes and can
      result in significant time loss from sports participation. Rehabilitation of
      athletes with injuries such as adductor strain, iliopsoas syndrome, and gluteal
      tendinopathy starts with identification of known risk factors for injury and
      comprehensive evaluation of the entire kinetic chain. Complex anatomy and
      overlapping pathologies often make it difficult to determine the primary cause of
      the pain and dysfunction. The purpose of this clinical commentary is to present
      an impairment-based, stepwise progression in evaluation and treatment of several
      common soft tissue injuries of the hip and pelvis. LEVEL OF EVIDENCE: 5.

PMID- 25383248
TI  - Recurrent hamstring injury: consideration following operative and non-operative
      management.
AB  - PURPOSE/BACKGROUND: Hamstring injuries are common at all levels of sport, however
      recurrence rates are disproportionate compared to other soft tissue injuries. Age
      and previous injury are supported in the literature as risk factors for hamstring
      injury; nonetheless, debate exists regarding modifiable risk factors. Restoration
      of peak torque length using lengthening eccentrics and core stability
      interventions appear to reduce incidence of re-injury. The purpose of this
      clinical commentary is to review examination techniques and rehabilitation
      considerations in order to identify important risk factors to reduce recurrence
      after hamstring strain and total rupture. DISCUSSION/RELATION TO CLINICAL
      PRACTICE: Novel clinical examination techniques both at time of acute injury and
      prior to return to sport may provide valuable prognostic information. Restoration
      of core stability, neuromuscular control and lengthening eccentric hamstring
      interventions are proposed key components to reduce hamstring re-injury. LEVELS
      OF EVIDENCE: Level 5.

PMID- 25383249
TI  - Rehabilitation after labral repair and femoroacetabular decompression: criteria
      based progression through the return to sport phase.
AB  - Rehabilitation following hip arthroscopy for femoroacetabular impingement (FAI)
      and labral-chondral dysfunction has evolved rapidly over the past 15 years. There
      have been multiple commentaries published on rehabilitation following hip
      arthroscopy without any published standardized objective criteria to address the
      advancement of the athlete through the phases of rehabilitation. The purpose of
      this clinical commentary is to describe a criteria driven algorithm for safe
      integration and return to sport rehabilitation following hip arthroscopy. The
      criteria based program allows for individuality of the athlete while providing
      guidance from early post-operative phases through late return to sport phases of
      rehabilitation. Emphasis is placed on the minimum criteria to advance including
      healing restraints, patient reported outcomes, range of motion, core and hip
      stability, postural control, symmetry with functional tasks and gait, strength,
      power, endurance, agility, and sport-specific tasks. Evidence to support the
      criteria will be offered as available. Despite limitations, this clinical
      commentary will offer a guideline for safe return to sport for the athlete while
      identifying areas for further investigation. LEVEL OF EVIDENCE: 5.

PMID- 25383250
TI  - Gait considerations in patients with femoroacetabular impingement.
AB  - The literature describing the characteristic features of femoroacetabular
      impingement (FAI) has been on the rise, increasing awareness of this pathology in
      the young, active population. The physical therapist should consider FAI as a
      contributing factor to anterior hip pain, impairments, and functional deficits of
      the lower quarter. The dynamic interplay of anatomical variations, pain, and
      muscle function and their effects on gait in patients with FAI, however, is
      poorly understood. Small sample populations and variability in radiological,
      demographic, and clinical presentations in those with FAI have precluded
      meaningful insight into gait analysis and FAI, reiterating the need for further
      research in this domain. The purpose of this clinical commentary is to review the
      literature that defines normal gait at the hip joint and abnormal gait as a
      result of FAI and labral pathology or surgery aimed at correcting it.
      Secondarily, the authors aim to offer clinicians a strategy to progress the post
      surgical patient to normal, unassisted gait while reducing the risk for anterior
      hip pain. Lastly, the authors of this commentary aim to identify specific areas
      for future research directed at therapeutic interventions in patients with FAI
      and those who have undergone surgery to correct it. LEVEL OF EVIDENCE: 5.

PMID- 25383251
TI  - Sports participation following total hip arthroplasty.
AB  - Total Hip Athroplasty (THA) is a common procedure in orthopedic surgery to
      address severe osteoarthritis (OA) in the hip joint. With the burgeoning "baby
      boomer" generation and older athletes who wish to return to competitive levels of
      sports, understanding how sporting activity affects THA outcomes is becoming
      exceptionally important. The purpose of this review is to characterize the
      current recommendations and risks for returning to sports after THA, as well as
      discuss the implications of the changing demographic and level of expectation on
      rehabilitation paradigms. Although the actual risks associated with participating
      in sports after THA are unknown, there are concerns that higher levels of
      physical activity after THA may increase risk for fracture, dislocation and poor
      long-term outcomes. Evidence surrounding the specific effect of sporting activity
      on wear after THA is conflicting. Newer alternatives such as metal-on-metal hip
      resurfacing are expected to provide better durability but there are concerns of
      systemic metal ions from mechanical wear, although the impact of these ions on
      patient health is not clear. Tracking outcomes in patients participating in
      higher level activities after THA presents a problem. Recently the High Activity
      Arthroplasty Score has been developed in response to the need to quantify higher
      level of physical activity and sports participation after joint arthroplasty.
      This measure has been shown to have a higher ceiling effect than other common
      outcome measures. There is little prospective evidence regarding the likelihood
      of poor clinical outcomes with higher level of sporting activity. There is some
      evidence to suggest that wear may be related to activity level, but the impact on
      clinical outcomes is conflicting. When advising an athlete considering returning
      to sport after THA, consider their preoperative activity level, current physical
      fitness, and specific history including bone quality, surgical approach and type
      of prosthesis. LEVEL OF EVIDENCE: 5.

PMID- 25383252
TI  - Conservative management of sports hernia in a professional golfer: a case report.
AB  - STUDY DESIGN: Case Report. BACKGROUND: Activity-limiting groin pain is relatively
      common in athletes who participate in sports which involve rapid or repetitive
      twisting, cutting, and/or kicking. Despite the reported prevalence of this
      condition in athletes, there is still much controversy as to the anatomical
      structures involved and most effective treatment approach. There is limited
      evidence favoring conservative management of sports hernia as opposed to surgical
      intervention in professional athletes, and there are no reports of sports hernia
      management in the professional golf population. The purpose of this case report
      is to describe the conservative management and decision making used with a
      professional golfer with symptoms consistent with a sports hernia which allowed
      for successful return to prior level of sport participation. CASE PRESENTATION:
      The subject of this case report is a professional golfer who developed lower
      abdominal and groin pain after changes in conditioning routine. Clinical
      presentation was consistent with a diagnosis of sports hernia. Rehabilitation of
      this athlete included a structured core muscle retraining program which utilized
      a step wise progression through the neurodevelopmental sequence in order to allow
      for development of neuromuscular control and stability required for return to
      golf. OUTCOME: This athlete was able to return to full golf participation after
      13 physical therapy visits over 4 weeks. DISCUSSION: The available evidence
      supports surgical intervention over conservative management in the treatment of
      sports hernia in the athletic population. A structured and comprehensive
      rehabilitation program addressing core muscle weakness and contributing
      impairments adjacent to injury may be a beneficial treatment option prior to
      surgical repair potentially allowing return to sport in some athletes. LEVELS OF
      EVIDENCE: 4.

PMID- 25383253
TI  - Enhanced emission of fluorophores on shrink-induced wrinkled composite
      structures.
AB  - We introduce a manufacturable and scalable method for creating tunable wrinkled
      ferromagnetic-metallic structures to enhance fluorescence signals. Thin layers of
      nickel (Ni) and gold (Au) were deposited onto a pre-stressed thermoplastic
      (shrink wrap film) polymer. Heating briefly forced the metal films to buckle when
      the thermoplastic retracted, resulting in multi-scale composite 'wrinkles'. This
      is the first demonstration of leveraging the plasmons in such hybrid
      nanostructures by metal enhanced fluorescence (MEF) in the near-infrared
      wavelengths. We observed more than three orders of magnitude enhancement in the
      fluorescence signal of a single molecule of goat anti-mouse immunoglobulin G
      (IgG) antibody conjugated to fluorescein isothiocyanate, FITC, (FITC-IgG) by two
      photon excitation with these structures. These large enhancements in the
      fluorescence signal at the nanoscale gaps between the composite wrinkles
      corresponded to shortened lifetimes due to localized surface plasmons. To
      characterize these structures, we combined fluctuation correlation spectroscopy
      (FCS), fluorescence lifetime imaging microscopy (FLIM), and two-photon microscopy
      to spatially and temporally map the hot spots with high resolution.

PMID- 25383254
TI  - The Intersection between Food Insecurity and Diabetes: A Review.
AB  - Access to sufficient, safe, and nutritious food not only affects the health of
      people who experience food insecurity, but also their ability to manage health
      conditions, such as diabetes. When people find it difficult to access sufficient
      food, tailoring their food selection to a diabetes regimen is even more
      difficult. Food insecurity in North America is consistently more prevalent among
      households with a person living with diabetes, and similarly, diabetes is also
      more prevalent in food-insecure households. Diabetes management can be stressful
      due to the many required responsibilities; when compounded with food insecurity,
      it becomes an even greater challenge. As a result, many food-insecure diabetics
      find themselves caught between competing priorities such as procuring food,
      prescribed medications and supplies for diabetes, and managing other living
      expenses, potentially worsening their condition and overall health. Healthcare
      providers should be aware and informed about the significant role that food
      security can play in the prevention and management of diabetes.

PMID- 25383255
TI  - The EPIC-InterAct Study: A Study of the Interplay between Genetic and Lifestyle
      Behavioral Factors on the Risk of Type 2 Diabetes in European Populations.
AB  - The rising prevalence of type 2 diabetes around the world and the global pattern
      of variation in risk between countries have been widely attributed to an
      interplay between rising rates of obesity and poor lifestyles, and genetic or
      developmental susceptibility to disease. Although this general hypothesis has
      been in existence for more than 50 years, the precise mechanisms that may explain
      it have remained uncertain. Advances in technology and the application of new
      methods in large scale population studies have made it possible to study these
      mechanisms. The InterAct project, funded by the European Commission, is a large
      case-cohort study which has verified 12,403 incident cases of type 2 diabetes,
      facilitating the study of genetic and lifestyle factors on the risk of type 2
      diabetes among European populations.

PMID- 25383257
TI  - Particle Filter Based Active Localization of Target and Needle in Robotic Image
      Guided Intervention Systems.
AB  - This paper presents a probabilistic method for active localization of needle and
      targets in robotic image guided interventions. Specifically, an active
      localization scenario where the system directly controls the imaging system to
      actively localize the needle and target locations using intra-operative medical
      imaging (e.g., computerized tomography and ultrasound imaging) is explored. In
      the proposed method, the active localization problem is posed as an information
      maximization problem, where the beliefs for the needle and target states are
      represented and estimated using particle filters. The proposed method is also
      validated using a simulation study.

PMID- 25383258
TI  - Policy Driven Development: Flexible Policy Insertion for Large Scale Systems.
AB  - The success of a software system depends critically on how well it reflects and
      adapts to stakeholder requirements. Traditional development methods often
      frustrate stakeholders by creating long latencies between requirement
      articulation and system deployment, especially in large scale systems. One source
      of latency is the maintenance of policy decisions encoded directly into system
      workflows at development time, including those involving access control and
      feature set selection. We created the Policy Driven Development (PDD) methodology
      to address these development latencies by enabling the flexible injection of
      decision points into existing workflows at runtime, thus enabling policy
      composition that integrates requirements furnished by multiple, oblivious
      stakeholder groups. Using PDD, we designed and implemented a production
      cyberinfrastructure that demonstrates policy and workflow injection that quickly
      implements stakeholder requirements, including features not contemplated in the
      original system design. PDD provides a path to quickly and cost effectively
      evolve such applications over a long lifetime.

PMID- 25383256
TI  - Prevention of Diabetes Through the Lifestyle Intervention: Lessons Learned from
      the Diabetes Prevention Program and Outcomes Study and its Translation to
      Practice.
AB  - A number of strategies have been used to delay or prevent the development of type
      2 diabetes mellitus (T2D) in high-risk adults. Among them were diet, exercise,
      medications and surgery. This report focuses on the nutritional lessons learned
      from implementation of the Intensive Lifestyle Intervention (ILI) in the DPP and
      its follow-up DPPOS that looked at weight loss through modification of diet and
      exercise. The Diabetes Prevention Program (DPP) is a large clinical trial,
      sponsored by the National Institutes of Health, designed to look at several
      strategies to prevent conversion to type 2 diabetes (T2D) by adults with
      prediabetes (IGT/IFG) including an Intensive Lifestyle Intervention (ILI). The
      ~3800 ethnically diverse participants (46% reported non-white race) were
      overweight, had impaired glucose tolerance (IGT) and impaired fasting glucose
      (IFG). Treatments were assigned randomly. The Diabetes Prevention Program
      Outcomes Study (DPPOS) is a follow up study evaluating the long-term outcomes of
      the clinical trial.

PMID- 25383259
TI  - Examining the spatially non-stationary associations between the second
      demographic transition and infant mortality: A Poisson GWR approach.
AB  - Based on ecological studies, second demographic transition (SDT) theorists
      concluded that some areas in the US were in vanguard of the SDT compared to
      others, implying spatial nonstationarity may be inherent in the SDT process.
      Linking the SDT to the infant mortality literature, we sought out to answer two
      related questions: Are the main components of the SDT, specifically marriage
      postponement, cohabitation, and divorce, associated with infant mortality? If
      yes, do these associations vary across the US? We applied global Poisson and
      geographically weighted Poisson regression (GWPR) models, a place-specific
      analytic approach, to county-level data in the contiguous US. After accounting
      for the racial/ethnic and socioeconomic compositions of counties and prenatal
      care utilization, we found (1) marriage postponement was negatively related to
      infant mortality in the southwestern states, but positively associated with
      infant mortality in parts of Indiana, Kentucky, and Tennessee, (2) cohabitation
      rates were positively related to infant mortality, and this relationship was
      stronger in California, coastal Virginia, and the Carolinas than other areas, and
      (3) a positive association between divorce rates and infant mortality in
      southwestern and northeastern areas of the US. These spatial patterns suggested
      that the associations between the SDT and infant mortality were stronger in the
      areas in vanguard of the SDT than in others. The comparison between global
      Poisson and GWPR results indicated that a place-specific spatial analysis not
      only fit the data better, but also provided insights into understanding the non
      stationarity of the associations between the SDT and infant mortality.

PMID- 25383260
TI  - Implementation of a Theory-based, Non-clinical Patient Navigator Program to
      Address Barriers in an Urban Cancer Center Setting.
AB  - Cancer patients face a myriad of psychosocial and practical issues. Especially
      challenging is the time from an initial diagnosis to the onset of treatment and
      patient navigation services are important to guide patients, especially
      underserved populations, through this maze of uncertainty. Here we report on the
      Pennsylvania Patient Navigator Demonstration Project (PaPND) designed to evaluate
      the acceptability, feasibility, and impact of a culturally and linguistically
      appropriate non-clinical navigator program. The development of the project, based
      on behavioral theory and community-based participatory research principles, is
      described. Forty-four cancer patients from diverse backgrounds participated,
      which included a baseline assessment, navigation services, and a four week and
      twelve week follow-up assessment. On average, participants experienced 1.8
      barriers with transportation and insurance issues the most common barriers. The
      majority (56%) of the barriers required more than an hour of the navigator's time
      to address, with insurance, transportation and caregiver/support issues requiring
      the most time. Overall patients were fairly satisfied with the navigation
      services. The findings showed improvement patient's stress-related thoughts,
      cognition (understanding of their disease), expectancies and beliefs or
      values/goals, as well as self-efficacy of managing cancer related issues from the
      baseline to follow-up assessments. The evaluation results suggest that providing
      and connecting cancer patients to appropriate information to improve their
      understanding of their diagnosis and recommended treatments needs to be
      addressed, and where the integration of non-clinical and clinical navigation is
      essential. In addition, more attention to the assessment of psychosocial issues,
      such as the patients' emotional worries, and more comprehensive training in these
      areas would enhance navigation programs.

PMID- 25383261
TI  - Periostin Expression is Altered in Aortic Valves in Smad6 Mutant Mice.
AB  - Smad6 is known to predominantly inhibit BMP signaling by negatively regulating
      the BMP signaling process. Therefore, Smad6 mutation potentially provides an
      important genetic model for investigating the role of BMP signaling in vivo.
      Periostin is a 90-kDA secreted extracellular matrix (ECM) protein and implicated
      in cardiac valve progenitor cell differentiation, maturation and adult aortic
      valve calcification in mice. We have previously reported periostin expression
      patterns during AV valve development in mice. Because periostin can play critical
      roles in aortic valve interstitial cell differentiation and can be correlated
      with adult valve disease pathogenesis, in the present study we specifically
      focused on periostin expression during outflow tract (OT) development and its
      expression within the adult mouse valves. We previously reported that periostin
      expression in valve progenitor cells was altered by exogenously adding BMP-2 in
      culture. In this study, we investigated whether expression of periostin and other
      valvulogenic ECM proteins was altered in Smad6-mutant newborn mice in vivo.
      Periostin protein was localized within OT during embryonic development in mice.
      At embryonic day (ED) 13.5, robust periostin expression was detected within the
      developing pulmonary trunk and developing pulmonary and aortic valves. Periostin
      expression remained intense in pulmonary and aortic valves up to the adult stage.
      Our immunohistochemical and immunointensity analyses revealed that periostin
      expression was significantly reduced in the aortic valves in Smad6-/- neonatal
      hearts. Versican expression was also significantly reduced in Smad6-/- aortic
      valves, whereas, hyaluronan deposition was not significantly altered in the Smad6
      /- neonatal valves. Expression of periostin and versican was less prominently
      affected in AV valves compared to the aortic valves, suggesting that a cell
      lineage/origin-dependent response to regulatory molecules may play a critical
      role in valve interstitial cell development and ECM protein expression.

PMID- 25383263
TI  - Skin conductance response during laboratory stress in combat veterans with
      posttraumatic stress disorder.
AB  - OBJECTIVE: The primary objective was to assess skin conductance response (SCR) to
      a laboratory stressor in combat veterans with posttraumatic stress disorder
      (PTSD) compared to controls. The secondary objective was to evaluate the
      relationship between SCR and PTSD symptom clusters. METHOD: 15 combat/ PTSD, 15
      combat/no PTSD, 15 no combat/no PTSD veterans had their SCR recording during
      aversive pictures from the International Affective Picture Scale. RESULTS: The
      groups had similar demographics and medical history (all p>.05). SCR was
      different between groups (F(2,42) = 4.34, p=.02). The combat/PTSD group had the
      highest response compared to both control groups. Numbing-avoiding was predictive
      of SCR (F(1,42)=12.72, p=.001), while re-experiencing and hyper-arousal were not
      (p's>.05). CONCLUSIONS: Increased SCR in the PTSD group validates previous
      studies. Numbing-avoiding PTSD cluster scores correlated with SCR values. These
      findings support current PTSD therapies that reduce avoidance behaviors.

PMID- 25383262
TI  - Unique and interactive effect of anxiety and depressive symptoms on cognitive and
      brain function in young and older adults.
AB  - OBJECTIVE: Depression and anxiety and are associated with cognitive deficits and
      brain changes, especially in older adults. Despite the frequent co-occurrence of
      these conditions, cognitive neuroscience studies examining comorbid depression
      and anxiety are limited. The goal of the present study was to examine the unique
      and combined effect of depressive and anxiety symptoms on cognitive and brain
      functioning in young and older adults. METHODS: Seventy-one healthy, community
      dwelling adults between the ages of 18 and 81 were administered a
      neuropsychological battery and completed the Center for Epidemiologic Studies
      Depression Scale (CES-D) and the trait form of the State-Trait Anxiety Inventory
      (STAI-T). A subset of 25 participants also underwent functional magnetic
      resonance imaging (fMRI) scanning while completing the n-back working memory
      task. RESULTS: Total depressive symptoms, depressed mood symptoms, and somatic
      symptoms were associated with deficits in speed, working memory and executive
      functions, especially in older adults. Symptoms of lack of well-being were not
      associated with any neuropsychological test. Anxiety was associated with better
      attention and working memory. Moreover, anxiety modified the relationship between
      depressive symptoms and executive functioning in older adults, as elevated
      depressive symptoms were associated with worse performance at low levels of
      anxiety, but not at higher anxiety levels. Similarly, analysis of fMRI data
      showed that total depressive symptoms and depressed mood symptoms were associated
      with decreased activity in the superior frontal gyrus at low anxiety levels, but
      not at high anxiety levels. CONCLUSION: Results confirm previous reports that
      subthreshold depression and anxiety impact cognitive and brain functioning and
      suggest that the interaction of depression and anxiety results in distinct
      cognitive and brain changes. Findings highlight the importance of assessing and
      controlling for symptoms of depression and anxiety in research studies of either
      condition.

PMID- 25383265
TI  - A simple, inexpensive, and field-relevant microcosm tidal simulator for use in
      marsh macrophyte studies.
AB  - PREMISE OF THE STUDY: A microcosm unit with tidal simulation was developed to
      address the challenge of maintaining ecologically relevant tidal regimes while
      performing controlled greenhouse experiments on smooth cordgrass, Spartina
      alterniflora. * METHODS AND RESULTS: We designed a simple, inexpensive, easily
      replicated microcosm unit with tidal simulation and tested whether S.
      alterniflora growth in microcosms with tidal simulation was similar to that of
      tidally influenced plants in the field on Sapelo Island, Georgia. After three
      months of exposure to either natural or simulated tidal treatment, plants in
      microcosms receiving tidal simulation had similar stem density, height, and above
      and belowground biomass to plants in field plots. * CONCLUSIONS: The tidal
      simulator developed may provide an inexpensive, effective method for conducting
      studies on S. alterniflora and other tidally influenced plants in controlled
      settings to be used not only to complement field studies, but also in locations
      without coastal access.

PMID- 25383264
TI  - PSEUDOXANTHOMA ELASTICUM: DIAGNOSTIC FEATURES, CLASSIFICATION, AND TREATMENT
      OPTIONS.
AB  - INTRODUCTION: Pseudoxanthoma elasticum (PXE), a multisystem orphan disease,
      clinically affects the skin, the eyes, and the cardiovascular system with
      considerable morbidity and mortality. The clinical manifestations reflect the
      underlying pathology consisting of ectopic mineralization of peripheral
      connective tissues. AREAS COVERED: The diagnostic criteria of PXE include
      characteristic clinical findings, together with histopathology of accumulation of
      pleiomorphic elastic structures in the dermis with progressive mineralization,
      and the presence of mutations in the ABCC6 gene. PXE-like cutaneous changes can
      also be encountered in other ectopic mineralization disorders, including
      generalized arterial calcification of infancy (GACI) caused by mutations in the
      ENPP1 gene. In some cases, overlapping clinical features of PXE/GACI, associated
      with mutations either in ABCC6 or ENPP1, have been noted. PXE demonstrates
      considerable inter- and intrafamilial heterogeneity, and consequently, accurate
      diagnosis is required for appropriate classification with prognostic
      implications. There is no effective and specific treatment for the systemic
      manifestations of PXE, but effective therapies to counteract the ocular
      complications are in current clinical use. EXPERT OPINION: A number of
      observations in the murine model, the Abcc6-/- mouse, have indicated that the
      mineral composition of diet, particularly the magnesium content, can influence
      the severity of the mineralization phenotype. These observations suggest that
      appropriate dietary interventions, coupled with lifestyle modifications,
      including smoking cessation, might alleviate the symptoms and improve the quality
      of life of individuals affected with this, currently intractable, orphan disease.

PMID- 25383266
TI  - Genome and metagenome sequencing: Using the human methyl-binding domain to
      partition genomic DNA derived from plant tissues.
AB  - PREMISE OF THE STUDY: Variation in the distribution of methylated CpG (methyl
      CpG) in genomic DNA (gDNA) across the tree of life is biologically interesting
      and useful in genomic studies. We illustrate the use of human methyl-CpG-binding
      domain (MBD2) to fractionate angiosperm DNA into eukaryotic nuclear (methyl-CpG
      rich) vs. organellar and prokaryotic (methyl-CpG-poor) elements for genomic and
      metagenomic sequencing projects. * METHODS: MBD2 has been used to enrich
      prokaryotic DNA in animal systems. Using gDNA from five model angiosperm species,
      we apply a similar approach to identify whether MBD2 can fractionate plant gDNA
      into methyl-CpG-depleted vs. enriched methyl-CpG elements. For each sample, three
      gDNA libraries were sequenced: (1) untreated gDNA, (2) a methyl-CpG-depleted
      fraction, and (3) a methyl-CpG-enriched fraction. * RESULTS: Relative to
      untreated gDNA, the methyl-depleted libraries showed a 3.2-11.2-fold and 3.4-11.3
      fold increase in chloroplast DNA (cpDNA) and mitochondrial DNA (mtDNA),
      respectively. Methyl-enriched fractions showed a 1.8-31.3-fold and 1.3-29.0-fold
      decrease in cpDNA and mtDNA, respectively. * DISCUSSION: The application of MBD2
      enabled fractionation of plant gDNA. The effectiveness was particularly striking
      for monocot gDNA (Poaceae). When sufficiently effective on a sample, this
      approach can increase the cost efficiency of sequencing plant genomes as well as
      prokaryotes living in or on plant tissues.

PMID- 25383267
TI  - A molecular identification protocol for roots of boreal forest tree species.
AB  - PREMISE OF THE STUDY: Roots play a key role in many ecological processes, yet
      our ability to identify species from bulk root samples is limited. Molecular
      tools may be used to identify species from root samples, but they have not yet
      been developed for most systems. Here we present a PCR-based method previously
      used to identify roots of grassland species, modified for use in boreal forests.
      * METHODS: We used repeatable interspecific size differences in fluorescent
      amplified fragment length polymorphisms of three noncoding chloroplast DNA
      regions to identify seven woody species common to boreal forests in Alberta,
      Canada. * RESULTS: Abies balsamea, Alnus crispa, Betula papyrifera, Pinus
      contorta, and Populus tremuloides were identifiable to species, while Picea
      glauca and Picea mariana were identifiable to genus. In mixtures of known
      composition of foliar DNA, species were identified with 98% accuracy using one
      region. Mixed root samples of unknown composition were identified with 100%
      accuracy; four species were identified using one region, while three species were
      identified using two regions. * DISCUSSION: This methodology is accurate,
      efficient, and inexpensive, and thus a valuable approach for ecological studies
      of roots. Furthermore, this method has now been validated for both grassland and
      boreal forest systems, and thus may also have applications in any plant
      community.

PMID- 25383268
TI  - Characterization of microsatellite markers for pinedrops, Pterospora andromedea
      (Ericaceae), from Illumina MiSeq sequencing.
AB  - PREMISE OF THE STUDY: Pterospora andromedea (Ericaceae) is a mycoheterotrophic
      plant endemic to North America with a disjunct distribution. Eastern populations
      are in decline compared to western populations. Microsatellite loci will allow
      comparison of genetic diversity in endangered to nonthreatened populations. *
      METHODS AND RESULTS: Illumina MiSeq sequencing resulted in development of 12
      polymorphic microsatellite loci from 63 perfect microsatellite loci tested. One
      polymorphic locus was obtained from a traditional enrichment method. These 13
      loci were screened across two western and two eastern populations. For western
      and eastern populations, respectively, number of alleles ranged from one to 10
      and one to four, and observed heterozygosity ranged from 0.000 to 0.389 and 0.000
      to 0.143. * CONCLUSIONS: These are the first microsatellite loci developed for
      Pterospora. They will be useful in conservation efforts of the eastern
      populations and for examination of population genetic parameters at different
      geographic scales and comparison with mycorrhizal fungal hosts.

PMID- 25383269
TI  - Development of multiplex microsatellite PCR panels for the seagrass Thalassia
      hemprichii (Hydrocharitaceae).
AB  - PREMISE OF THE STUDY: New microsatellites were developed for the seagrass
      Thalassia hemprichii (Hydrocharitaceae), a long-lived seagrass species that is
      found throughout the shallow waters of tropical and subtropical Indo-West
      Pacific. Three multiplex PCR panels were designed utilizing new and previously
      developed markers, resulting in a toolkit for generating a 16-locus genotype. *
      METHODS AND RESULTS: Through the use of microsatellite enrichment and next
      generation sequencing, 16 new, validated, polymorphic microsatellite markers were
      isolated. Diversity was between two and four alleles per locus totaling 36
      alleles. These markers, plus previously developed microsatellite markers for T.
      hemprichii and T. testudinum, were tested for suitability in multiplex PCR
      panels. * CONCLUSIONS: The generation of an easily replicated suite of multiplex
      panels of codominant molecular markers will allow for high-resolution and
      detailed genetic structure analysis and clonality assessment with minimal
      genotyping costs. We suggest the establishment of a T. hemprichii primer
      convention for the unification of future data sets.

PMID- 25383270
TI  - Isolation and characterization of polymorphic microsatellite loci in Spondias
      radlkoferi (Anacardiaceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for Spondias
      radlkoferi to assess the impact of primate seed dispersal on the genetic
      diversity and structure of this important tree species of Anacardiaceae. *
      METHODS AND RESULTS: Fourteen polymorphic loci were isolated from S. radlkoferi
      through 454 GS-FLX Titanium pyrosequencing of genomic DNA. The number of alleles
      ranged from three to 12. The observed and expected heterozygosities ranged from
      0.382 to 1.00 and from 0.353 to 0.733, respectively. The amplification was also
      successful in S. mombin and two genera of Anacardiaceae: Rhus aromatica and
      Toxicodendron radicans. * CONCLUSIONS: These microsatellite loci will be useful
      to assess the genetic diversity and population structure of S. radlkoferi and
      related species, and will allow us to investigate the effects of seed dispersal
      by spider monkeys (Ateles geoffroyi) on the genetic structure and diversity of S.
      radlkoferi populations in a fragmented rainforest.

PMID- 25383271
TI  - Microsatellite loci in two epiphytic lichens with contrasting dispersal modes:
      Nephroma laevigatum and N. parile (Nephromataceae).
AB  - PREMISE OF THE STUDY: Microsatellite markers were characterized for two
      epiphytic cyanolichens, Nephroma laevigatum and N. parile (Nephromataceae), and
      will be used to investigate population structure and estimate gene flow among
      populations of these two closely related species with contrasting dispersal
      modes. * METHODS AND RESULTS: Twelve and 14 microsatellite loci were
      characterized for N. laevigatum and N. parile, respectively. Allele number in N.
      laevigatum ranged from three to 13 per locus, while in N. parile there were from
      two to six alleles per locus. As expected, the sexually reproducing N. laevigatum
      had higher genetic diversity than the predominantly asexual N. parile. *
      CONCLUSIONS: This new set of markers is suitable for studying population
      structure and providing insights into gene flow among populations and for
      understanding processes of diversification. Compared between the species, they
      will facilitate an understanding of the influence of contrasting reproductive
      strategies on population and community structure.

PMID- 25383272
TI  - 3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a Selective
      Antagonist of Sphingosine-1-phospahte Receptor Subtype 1, Enhances AMD3100
      stimulated Mobilization of Hematopoietic Stem Progenitor Cells in Animals.
AB  - Sphingosine-1-phosphate (S1P), a serum-borne bioactive lipid, regulates various
      physiological functions. We observed that the S1P receptor subtype 1 (S1P1), a
      high affinity G-protein coupled receptor of S1P, is the major S1P receptor
      expressed in the Kit+/Sca-1+/Lin- (KSL) hematopoietic stem progenitor cells
      (HSPCs, KSL-HSPCs). In this study, we investigate function of S1P1 receptors in
      the regulation of HSPC mobilization in animals. Treatment with SEW2871, a
      specific agonist of S1P1, had no effect on KSL-HSPC mobilization. In addition,
      mice pretreated with SEW2871 followed by AMD3100, a well-known activator of KSL
      HSPC mobilization by antagonizing the stromal-derived factor-1 (SDF-1)/C-X-C
      chemokine receptor type 4 (CXCR4) signaling axis, did not enhance the AMD3100
      induced KSL-HSPC mobilization. In contrast, pretreatment of (R)-3-amino-4-(3
      hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a selective antagonist of
      S1P1, significantly augments AMD3100-induced KSL-HSPC mobilization into
      peripheral blood. The inactive enantiomer W140 was incapable of enhancing the
      AMD3100-induced KSL-HSPC mobilization. Moreover, treatment with selective
      antagonists for S1P2 and S1P3 had no effects on AMD3100-mediated KSL-HSPC
      mobilization. Collectively, our data suggest that S1P/S1P1 signaling regulates
      the SDF-1/CXCR4-mediated retention of KSL-HSPCs in bone marrow microenvironment.

PMID- 25383273
TI  - On the structure of grain/interphase boundaries and interfaces.
AB  - Grain/interphase boundaries/interfaces of varying misorientations, free volume
      fractions, curvatures and irregularities are present in materials, both 3D and
      2D, regardless of whether these materials are crystalline or amorphous/glassy.
      Therefore, a question arises about the central idea on which a general
      description of grain/interphase boundaries/interfaces can and should be based. It
      is suggested that a generalized model of a structural/basic unit (crystalline,
      non-crystalline or of any scale), which depends on the interatomic (including
      electronic) interactions, the spatial distribution of the atoms and electrons,
      the number of atoms and free volume fraction present in the structural/basic unit
      and the experimental conditions should serve the purpose. As the development of a
      quantitative model, which reflects the effects of all these variables is
      difficult, slightly defective material boundaries are often modeled by treating
      the entire boundary as planar and by using the concepts of crystallography. For
      highly disordered boundaries, a description in terms of a representative volume,
      made up of a non-crystalline basic unit or a combination of such units, which
      depend on interatomic (including electronic) interactions and forces, is
      advocated. The size, shape, free volume fraction and number of atoms in the
      representative volume could differ with material composition and experimental
      conditions. In the latter approach, it is assumed that all processes connected to
      a problem on hand is contained within this representative volume. The unresolved
      issues are identified. 

PMID- 25383274
TI  - Precise quantification of silica and ceria nanoparticle uptake revealed by 3D
      fluorescence microscopy.
AB  - Particle_in_Cell-3D is a powerful method to quantify the cellular uptake of
      nanoparticles. It combines the advantages of confocal fluorescence microscopy
      with fast and precise semi-automatic image analysis. In this work we present how
      this method was applied to investigate the impact of 310 nm silica nanoparticles
      on human vascular endothelial cells (HUVEC) in comparison to a cancer cell line
      derived from the cervix carcinoma (HeLa). The absolute number of intracellular
      silica nanoparticles within the first 24 h was determined and shown to be cell
      type-dependent. As a second case study, Particle_in_Cell-3D was used to assess
      the uptake kinetics of 8 nm and 30 nm ceria nanoparticles interacting with human
      microvascular endothelial cells (HMEC-1). These small nanoparticles formed
      agglomerates in biological medium, and the particles that were in effective
      contact with cells had a mean diameter of 417 nm and 316 nm, respectively. A
      significant particle size-dependent effect was observed after 48 h of
      interaction, and the number of intracellular particles was more than four times
      larger for the 316 nm agglomerates. Interestingly, our results show that for both
      particle sizes there is a maximum dose of intracellular nanoparticles at about 24
      h. One of the causes for such an interesting and unusual uptake behavior could be
      cell division. 

PMID- 25383276
TI  - Multi-frequency tapping-mode atomic force microscopy beyond three eigenmodes in
      ambient air.
AB  - We present an exploratory study of multimodal tapping-mode atomic force
      microscopy driving more than three cantilever eigenmodes. We present tetramodal
      (4-eigenmode) imaging experiments conducted on a thin polytetrafluoroethylene
      (PTFE) film and computational simulations of pentamodal (5-eigenmode) cantilever
      dynamics and spectroscopy, focusing on the case of large amplitude ratios between
      the fundamental eigenmode and the higher eigenmodes. We discuss the dynamic
      complexities of the tip response in time and frequency space, as well as the
      average amplitude and phase response. We also illustrate typical images and
      spectroscopy curves and provide a very brief description of the observed
      contrast. Overall, our findings are promising in that they help to open the door
      to increasing sophistication and greater versatility in multi-frequency AFM
      through the incorporation of a larger number of driven eigenmodes, and in
      highlighting specific future research opportunities. 

PMID- 25383275
TI  - Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and
      macrophages.
AB  - Precise knowledge regarding cellular uptake of nanoparticles is of great
      importance for future biomedical applications. Four different endocytotic uptake
      mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin
      mediated endocytosis, were investigated using a mouse macrophage (J774A.1) and a
      human alveolar epithelial type II cell line (A549). In order to deduce the
      involved pathway in nanoparticle uptake, selected inhibitors specific for one of
      the endocytotic pathways were optimized regarding concentration and incubation
      time in combination with fluorescently tagged marker proteins. Qualitative
      immunolocalization showed that J774A.1 cells highly expressed the lipid raft
      related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1.
      A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1
      uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene
      nanoparticles by J774A.1 macrophages when actin polymerization and clathrin
      coated pit formation was blocked. From this result, it is suggested that
      macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play
      a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549
      cells was inhibited after depletion of cholesterol in the plasma membrane
      (preventing caveolin-mediated endocytosis) and inhibition of clathrin-coated
      vesicles (preventing clathrin-mediated endocytosis). Our data showed that a
      combination of several distinguishable endocytotic uptake mechanisms are involved
      in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and
      epithelial cell line. 

PMID- 25383277
TI  - Probing viscoelastic surfaces with bimodal tapping-mode atomic force microscopy:
      Underlying physics and observables for a standard linear solid model.
AB  - This paper presents computational simulations of single-mode and bimodal atomic
      force microscopy (AFM) with particular focus on the viscoelastic interactions
      occurring during tip-sample impact. The surface is modeled by using a standard
      linear solid model, which is the simplest system that can reproduce creep
      compliance and stress relaxation, which are fundamental behaviors exhibited by
      viscoelastic surfaces. The relaxation of the surface in combination with the
      complexities of bimodal tip-sample impacts gives rise to unique dynamic behaviors
      that have important consequences with regards to the acquisition of quantitative
      relationships between the sample properties and the AFM observables. The physics
      of the tip-sample interactions and its effect on the observables are illustrated
      and discussed, and a brief research outlook on viscoelasticity measurement with
      intermittent-contact AFM is provided. 

PMID- 25383278
TI  - The influence of molecular mobility on the properties of networks of gold
      nanoparticles and organic ligands.
AB  - We prepare and investigate two-dimensional (2D) single-layer arrays and
      multilayered networks of gold nanoparticles derivatized with conjugated hetero
      aromatic molecules, i.e., S-(4-{[2,6-bipyrazol-1-yl)pyrid-4
      yl]ethynyl}phenyl)thiolate (herein S-BPP), as capping ligands. These structures
      are fabricated by a combination of self-assembly and microcontact printing
      techniques, and are characterized by electron microscopy, UV-visible spectroscopy
      and Raman spectroscopy. Selective binding of the S-BPP molecules to the gold
      nanoparticles through Au-S bonds is found, with no evidence for the formation of
      N-Au bonds between the pyridine or pyrazole groups of BPP and the gold surface.
      Subtle, but significant shifts with temperature of specific Raman S-BPP modes are
      also observed. We attribute these to dynamic changes in the orientation and/or
      increased mobility of the molecules on the gold nanoparticle facets. As for their
      conductance, the temperature-dependence for S-BPP networks differs significantly
      from standard alkanethiol-capped networks, especially above 220 K. Relating the
      latter two observations, we propose that dynamic changes in the molecular layers
      effectively lower the molecular tunnel barrier for BPP-based arrays at higher
      temperatures. 

PMID- 25383280
TI  - A study on the consequence of swift heavy ion irradiation of Zn-silica
      nanocomposite thin films: electronic sputtering.
AB  - Zn-silica nanocomposite thin films with varying Zn metal content, deposited by
      atom beam sputtering technique were subjected to 100 MeV Ag ion irradiation.
      Rutherford backscattering spectrometry reveals the loss of Zn with irradiation,
      which is observed to be greater from thin films with lower Zn content. The
      sputtered species collected on carbon-coated transmission electron microscopy
      (TEM) grids consist of Zn nanoparticles of sizes comparable to those present in
      the nanocomposite thin film. The process of size-dependent electronic sputtering
      of Zn is explained on the basis of an inelastic thermal spike model. The
      possibility of direct cluster emission is explained by pressure spike built
      inside the track, initiated by a temperature spike. 

PMID- 25383279
TI  - Non-covalent and reversible functionalization of carbon nanotubes.
AB  - Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose
      innovative nanoscaffolds for applications in fields such as material science,
      drug delivery and diagnostic applications. Their versatile physicochemical
      features are nonetheless limited by their scarce solubilization in both aqueous
      and organic solvents. In order to overcome this drawback CNTs can be easily non
      covalently functionalized with different dispersants. In the present review we
      focus on the peculiar hydrophobic character of pristine CNTs that prevent them to
      easily disperse in organic solvents. We report some interesting examples of CNTs
      dispersants with the aim to highlight the essential features a molecule should
      possess in order to act as a good carbon nanotube dispersant both in water and in
      organic solvents. The review pinpoints also a few examples of dispersant design.
      The last section is devoted to the exploitation of the major quality of non
      covalent functionalization that is its reversibility and the possibility to
      obtain stimuli-responsive precipitation or dispersion of CNTs. 

PMID- 25383281
TI  - In vitro and in vivo interactions of selected nanoparticles with rodent serum
      proteins and their consequences in biokinetics.
AB  - When particles incorporated within a mammalian organism come into contact with
      body fluids they will bind to soluble proteins or those within cellular membranes
      forming what is called a protein corona. This binding process is very complex and
      highly dynamic due to the plethora of proteins with different affinities and
      fractions in different body fluids and the large variation of compounds and
      structures of the particle surface. Interestingly, in the case of nanoparticles
      (NP) this protein corona is well suited to provide a guiding vehicle of
      translocation within body fluids and across membranes. This NP translocation may
      subsequently lead to accumulation in various organs and tissues and their
      respective cell types that are not expected to accumulate such tiny foreign
      bodies. Because of this unprecedented NP accumulation, potentially adverse
      biological responses in tissues and cells cannot be neglected a priori but
      require thorough investigations. Therefore, we studied the interactions and
      protein binding kinetics of blood serum proteins with a number of engineered NP
      as a function of their physicochemical properties. Here we show by in vitro
      incubation tests that the binding capacity of different engineered NP
      (polystyrene, elemental carbon) for selected serum proteins depends strongly on
      the NP size and the properties of engineered surface modifications. In the
      following attempt, we studied systematically the effect of the size (5, 15, 80
      nm) of gold spheres (AuNP), surface-modified with the same ionic ligand; as well
      as 5 nm AuNP with five different surface modifications on the binding to serum
      proteins by using proteomics analyses. We found that the binding of numerous
      serum proteins depended strongly on the physicochemical properties of the AuNP.
      These in vitro results helped us substantially in the interpretation of our
      numerous in vivo biokinetics studies performed in rodents using the same NP.
      These had shown that not only the physicochemical properties determined the AuNP
      translocation from the organ of intake towards blood circulation and subsequent
      accumulation in secondary organs and tissues but also the the transport across
      organ membranes depended on the route of AuNP application. Our in vitro protein
      binding studies support the notion that the observed differences in in vivo
      biokinetics are mediated by the NP protein corona and its dynamical change during
      AuNP translocation in fluids and across membranes within the organism. 

PMID- 25383282
TI  - Nanocrystalline ceria coatings on solid oxide fuel cell anodes: the role of
      organic surfactant pretreatments on coating microstructures and sulfur tolerance.
AB  - Treatments with organic surfactants, followed by the deposition of
      nanocrystalline ceria coatings from aqueous solution, were applied to anodes of
      solid oxide fuel cells. The cells were then operated in hydrogen/nitrogen fuel
      streams with H2S contents ranging from 0 to 500 ppm. Two surfactant treatments
      were studied: immersion in dodecanethiol, and a multi-step conversion of a siloxy
      anchored alkyl bromide to a sulfonate functionality. The ceria coatings deposited
      after the thiol pretreatment, and on anodes with no pretreatment, were continuous
      and uniform, with thicknesses of 60-170 nm and 100-140 nm, respectively, and
      those cells exhibited better lifetime performance and sulfur tolerance compared
      to cells with untreated anodes and anodes with ceria coatings deposited after the
      sulfonate pretreatment. Possible explanations for the effects of the treatments
      on the structure of the coatings, and for the effects of the coatings on the
      performance of the cells, are discussed. 

PMID- 25383283
TI  - Equilibrium states and stability of pre-tensioned adhesive tapes.
AB  - In the present paper we propose a generalization of the model developed in
      Afferrante, L.; Carbone, G.; Demelio, G.; Pugno, N. Tribol. Lett. 2013, 52, 439
      447 to take into account the effect of the pre-tension in the tape. A detailed
      analysis of the peeling process shows the existence of two possible detachment
      regimes: one being stable and the other being unstable, depending on the initial
      configuration of the tape. In the stability region, as the peeling process
      advances, the peeling angle reaches a limiting value, which only depends on the
      geometry, on the elastic modulus of the tape and on the surface energy of
      adhesion. Vice versa, in the unstable region, depending on the initial conditions
      of the system, the tape can evolve towards a state of complete detachment or fail
      before reaching a state of equilibrium with complete adhesion. We find that the
      presence of pre-tension in the tape does not modify the stability behavior of the
      system, but significantly affects the pull-off force which can be sustained by
      the tape before complete detachment. Moreover, above a critical value of the pre
      tension, which depends on the surface energy of adhesion, the tape will tend to
      spontaneously detach from the substrate. In this case, an external force is
      necessary to avoid spontaneous detachment and make the tape adhering to the
      substrate. 

PMID- 25383284
TI  - Influence of surface-modified maghemite nanoparticles on in vitro survival of
      human stem cells.
AB  - Surface-modified maghemite (gamma-Fe2O3) nanoparticles were obtained by using a
      conventional precipitation method and coated with D-mannose and poly(N,N
      dimethylacrylamide). Both the initial and the modified particles were
      characterized by transmission electron microscopy and dynamic light scattering
      with regard to morphology, particle size and polydispersity. In vitro survival of
      human stem cells was then investigated by using the methyl thiazolyl tetrazolium
      (MTT) assay, which showed that D-mannose- and poly(N,N-dimethylacrylamide)-coated
      gamma-Fe2O3 particles exhibit much lower level of cytotoxicity than the non
      coated gamma-Fe2O3. 

PMID- 25383285
TI  - Quasi-1D physics in metal-organic frameworks: MIL-47(V) from first principles.
AB  - The geometric and electronic structure of the MIL-47(V) metal-organic framework
      (MOF) is investigated by using ab initio density functional theory (DFT)
      calculations. Special focus is placed on the relation between the spin
      configuration and the properties of the MOF. The ground state is found to be
      antiferromagnetic, with an equilibrium volume of 1554.70 A(3). The transition
      pressure of the pressure-induced large-pore-to-narrow-pore phase transition is
      calculated to be 82 MPa and 124 MPa for systems with ferromagnetic and
      antiferromagnetic chains, respectively. For a mixed system, the transition
      pressure is found to be a weighted average of the ferromagnetic and
      antiferromagnetic transition pressures. Mapping DFT energies onto a simple-spin
      Hamiltonian shows both the intra- and inter-chain coupling to be
      antiferromagnetic, with the latter coupling constant being two orders of
      magnitude smaller than the former, suggesting the MIL-47(V) to present quasi-1D
      behavior. The electronic structure of the different spin configurations is
      investigated and it shows that the band gap position varies strongly with the
      spin configuration. The valence and conduction bands show a clear V d-character.
      In addition, these bands are flat in directions orthogonal to VO6 chains, while
      showing dispersion along the the direction of the VO6 chains, similar as for
      other quasi-1D materials. 

PMID- 25383286
TI  - Controlling the dispersion of supported polyoxometalate heterogeneous catalysts:
      impact of hybridization and the role of hydrophilicity-hydrophobicity balance and
      supramolecularity.
AB  - The hybridization of polyoxometalates (POMs) through an organic-inorganic
      association offers several processing advantages in the design of heterogeneous
      catalysts. A clear understanding of the organization of these hybrid materials on
      solid surfaces is necessary to optimise their properties. Herein, we report for
      the first time the organization of Keggin phosphotungstic [PW12O40](3-) and Wells
      Dawson (WD) phosphomolybdic [P2Mo18O62](6-) anions deposited on mica
      (hydrophilic), and highly oriented pyrolytic graphite (HOPG) (hydrophobic)
      surfaces. Next, the supramolecular organization of the organic-inorganic hybrid
      materials formed from the association of POM anions and
      dimethyldioctadecylammonium bromide (DODA) is investigated as a function of the
      hydrophilic or hydrophobic nature of the surfaces. The height of the Keggin-POM
      anions, measured with tapping mode (TM-AFM) is always in good agreement with the
      molecular dimension of symmetric Keggin-POM anions (ca. 1 nm). However, the
      asymmetric WD-POM anions form monolayer assemblies on the surfaces with the
      orientation of their long molecular axis (ca. 1.6 nm) depending on the
      hydrophilic or hydrophobic properties of the substrate. Namely, the long axis is
      parallel on mica, and perpendicular on HOPG. When hybridized with DODA, the
      organization of the hybrid material is dictated by the interaction of the alkyl
      side chains of DODA with the substrate surface. On HOPG, the DODA-POM hybrid
      forms small domains of epitaxially arranged straight nanorod structures with
      their orientation parallel to each other. Conversely, randomly distributed
      nanospheres are formed when the hybrid material is deposited on freshly cleaved
      mica. Finally, a UV-ozone treatment of the hybrid material allows one to obtain
      highly dispersed isolated POM entities on both hydrophilic and hydrophobic
      surfaces. The hybridization strategy to prevent the clustering of POMs on various
      supports would enable to develop highly dispersed POM-based heterogeneous
      catalysts with enhanced functionalities. 

PMID- 25383287
TI  - Experimental techniques for the characterization of carbon nanoparticles - a
      brief overview.
AB  - THE REVIEW OF FOUR EXPERIMENTAL METHODS: X-ray diffraction, Raman spectroscopy,
      electron paramagnetic resonance and four-point electrical conductivity
      measurements is presented to characterize carbon nanoparticles. Two types of
      carbon nanoparticle systems are discussed: one comprising the powder of
      individual carbon nanoparticles and the second as a structurally interconnected
      nanoparticle matrix in the form of a fiber. X-ray diffraction and Raman
      spectroscopy reveal the atomic structure of the carbon nanoparticles and allow
      for observation of the changes in the quasi-graphitic ordering induced by
      ultrasonic irradiation and with the so-called quasi-high pressure effect under
      adsorption conditions. Structural changes have strong influence on the electronic
      properties, especially the localization of charge carriers within the
      nanoparticles, which can be observed with the EPR technique. This in turn can be
      well-correlated with the four-point electrical conductivity measurements which
      directly show the character of the charge carrier transport within the examined
      structures.

PMID- 25383288
TI  - Controlling the optical and structural properties of ZnS-AgInS2 nanocrystals by
      using a photo-induced process.
AB  - ZnS-AgInS2 (ZAIS) solid-solution nanocrystals are promising materials for
      nanophotonic devices in the visible region because of their low toxicity and good
      emission properties. We developed a technique of photo-induced synthesis to
      control the size and composition of the ZAIS nanocrystals. This method
      successfully decreased the defect levels, as well as the size and size variation
      of ZAIS nanocrystals by controlling the excitation wavelength during synthesis.
      Detailed analysis of transmission electron microscope images confirmed that the
      photo-induced synthesis yielded a high crystallinity of the ZAIS nanocrystals
      with small variations in size and content. 

PMID- 25383289
TI  - The surface properties of nanoparticles determine the agglomeration state and the
      size of the particles under physiological conditions.
AB  - Due to the recent widespread application of nanomaterials to biological systems,
      a careful consideration of their physiological impact is required. This demands
      an understanding of the complex processes at the bio-nano interface. Therefore, a
      comprehensive and accurate characterization of the material under physiological
      conditions is crucial to correlate the observed biological impact with defined
      colloidal properties. As promising candidates for biomedical applications, two
      SiO2-based nanomaterial systems were chosen for extensive size characterization
      to investigate the agglomeration behavior under physiological conditions. To
      combine the benefits of different characterization techniques and to compensate
      for their respective drawbacks, transmission electron microscopy, dynamic light
      scattering and asymmetric flow field-flow fractionation were applied. The
      investigated particle systems were (i) negatively charged silica particles and
      (ii) poly(organosiloxane) particles offering variable surface modification
      opportunities (positively charged, polymer coated). It is shown that the surface
      properties primarily determine the agglomeration state of the particles and
      therefore their effective size, especially under physiological conditions. Thus,
      the biological identity of a nanomaterial is clearly influenced by
      differentiating surface properties. 

PMID- 25383290
TI  - Silicon and germanium nanocrystals: properties and characterization.
AB  - Group-IV nanocrystals have emerged as a promising group of materials that extends
      the realm of application of bulk diamond, silicon, germanium and related
      materials beyond their traditional boundaries. Over the last two decades of
      research, their potential for application in areas such as optoelectronic
      applications and memory devices has been progressively unraveled. Nevertheless,
      new challenges with no parallel in the respective bulk material counterparts have
      arisen. In this review, we consider what has been achieved and what are the
      current limitations with regard to growth, characterization and modeling of
      silicon and germanium nanocrystals and related materials. 

PMID- 25383291
TI  - Biocompatibility of cerium dioxide and silicon dioxide nanoparticles with
      endothelial cells.
AB  - Cerium dioxide (CeO2) and silicon dioxide (SiO2) nanoparticles are of widespread
      use in modern life. This means that human beings are markedly exposed to them in
      their everyday life. Once passing biological barriers, these nanoparticles are
      expected to interact with endothelial cells, leading to systemic alterations with
      distinct influences on human health. In the present study we observed the
      metabolic impact of differently sized CeO2 (8 nm; 35 nm) and SiO2 nanoparticles
      (117 nm; 315 nm) on immortalized human microvascular (HMEC-1) and primary
      macrovascular endothelial cells (HUVEC), with particular focus on the CeO2
      nanoparticles. The characterization of the CeO2 nanoparticles in cell culture
      media with varying serum content indicated a steric stabilization of
      nanoparticles due to interaction with proteins. After cellular uptake, the CeO2
      nanoparticles were localized around the nucleus in a ring-shaped manner. The
      nanoparticles revealed concentration and time, but no size-dependent effects on
      the cellular adenosine triphosphate levels. HUVEC reacted more sensitively to
      CeO2 nanoparticle exposure than HMEC-1. This effect was also observed in relation
      to cytokine release after nanoparticle treatment. The CeO2 nanoparticles
      exhibited a specific impact on the release of diverse proteins. Namely, a slight
      trend towards pro-inflammatory effects, a slight pro-thrombotic impact, and an
      increase of reactive oxygen species after nanoparticle exposure were observed
      with increasing incubation time. For SiO2 nanoparticles, concentration- and time
      dependent effects on the metabolic activity as well as pro-inflammatory reactions
      were detectable. In general, the effects of the investigated nanoparticles on
      endothelial cells were rather insignificant, since the alterations on the
      metabolic cell activity became visible at a nanoparticle concentration that is by
      far higher than those expected to occur in the in vivo situation (CeO2
      nanoparticles: 100 ug/mL; SiO2 nanoparticles: 10 ug/mL). 

PMID- 25383292
TI  - Mechanical properties of sol-gel derived SiO2 nanotubes.
AB  - The mechanical properties of thick-walled SiO2 nanotubes (NTs) prepared by a sol
      gel method while using Ag nanowires (NWs) as templates were measured by using
      different methods. In situ scanning electron microscopy (SEM) cantilever beam
      bending tests were carried out by using a nanomanipulator equipped with a force
      sensor in order to investigate plasticity and flexural response of NTs.
      Nanoindentation and three point bending tests of NTs were performed by atomic
      force microscopy (AFM) under ambient conditions. Half-suspended and three-point
      bending tests were processed in the framework of linear elasticity theory. Finite
      element method simulations were used to extract Young's modulus values from the
      nanoindentation data. Finally, the Young's moduli of SiO2 NTs measured by
      different methods were compared and discussed. 

PMID- 25383293
TI  - A reproducible number-based sizing method for pigment-grade titanium dioxide.
AB  - A strong demand for reliable characterization methods of particulate materials is
      triggered by the prospect of forthcoming national and international regulations
      concerning the classification of nanomaterials. Scientific efforts towards
      standardized number-based sizing methods have so far been concentrated on model
      systems, such as spherical gold or silica nanoparticles. However, for industrial
      particulate materials, which are typically targets of regulatory efforts,
      characterisation is in most cases complicated by irregular particle shapes, broad
      size distributions and a strong tendency to agglomeration. Reliable sizing
      methods that overcome these obstacles, and are practical for industrial use, are
      still lacking. By using the example of titanium dioxide, this paper shows that
      both necessities are well met by the sophisticated counting algorithm presented
      here, which is based on the imaging of polished sections of embedded particles
      and subsequent automated image analysis. The data presented demonstrate that the
      typical difficulties of sizing processes are overcome by the proposed method of
      sample preparation and image analysis. In other words, a robust, reproducible and
      statistically reliable method is presented, which leads to a number-based size
      distribution of pigment-grade titanium dioxide, for example, and therefore allows
      reliable classification of this material according to forthcoming regulations. 

PMID- 25383294
TI  - Real-time monitoring of calcium carbonate and cationic peptide deposition on
      carboxylate-SAM using a microfluidic SAW biosensor.
AB  - A microfluidic biosensor with surface acoustic wave technology was used in this
      study to monitor the interaction of calcium carbonate with standard carboxylate
      self-assembled monolayer sensor chips. Different fluids, with and without
      biomolecular components, were investigated. The pH-dependent surface interactions
      of two bio-inspired cationic peptides, AS8 and ES9, which are similar to an
      extracellular domain of the chitin synthase involved in mollusc shell formation,
      were also investigated in a biological buffer system. A range of experimental
      conditions are described that are suitable to study non-covalent molecular
      interactions in the presence of ionic substances, such as, mineral precursors
      below the solubility equilibrium. The peptide ES9, equal to the mollusc chitin
      synthase epitope, is less sensitive to changes in pH than its counterpart AS8
      with a penta-lysine core, which lacks the flanking acidic residues. This study
      demonstrates the extraordinary potential of microfluidic surface acoustic wave
      biosensors to significantly expand our experimental capabilities for studying the
      principles underlying biomineralization in vitro. 

PMID- 25383295
TI  - Room temperature, ppb-level NO2 gas sensing of multiple-networked ZnSe nanowire
      sensors under UV illumination.
AB  - Reports of the gas sensing properties of ZnSe are few, presumably because of the
      decomposition and oxidation of ZnSe at high temperatures. In this study, ZnSe
      nanowires were synthesized by the thermal evaporation of ZnSe powders and the
      sensing performance of multiple-networked ZnSe nanowire sensors toward NO2 gas
      was examined. The results showed that ZnSe might be a promising gas sensor
      material if it is used at room temperature. The response of the ZnSe nanowires to
      50 ppb-5 ppm NO2 at room temperature under dark and UV illumination conditions
      were 101-102% and 113-234%, respectively. The responses of the ZnSe nanowires to
      5 ppm NO2 increased from 102 to 234% with increasing UV illumination intensity
      from 0 to 1.2 mW/cm(2). The response of the ZnSe nanowires was stronger than or
      comparable to that of typical metal oxide semiconductors reported in the
      literature, which require higher NO2 concentrations and operate at higher
      temperatures. The origin of the enhanced response of the ZnSe nanowires towards
      NO2 under UV illumination is also discussed. 

PMID- 25383296
TI  - Electronic and electrochemical doping of graphene by surface adsorbates.
AB  - Many potential applications of graphene require its precise and controllable
      doping with charge carriers. Being a two-dimensional material graphene is
      extremely sensitive to surface adsorbates, so its electronic properties can be
      effectively modified by deposition of different atoms and molecules. In this
      paper, we review two mechanisms of graphene doping by surface adsorbates, namely
      electronic and electrochemical doping. Although, electronic doping has been
      extensively studied and discussed in the literature, much less attention has been
      paid to electrochemical doping. This mechanism can, however, explain the doping
      of graphene by adsorbates for which no charge transfer is expected within the
      electronic doping model. In addition, electrochemical doping is in the origin of
      the hysteresis effects often observed in graphene-based field effect transistors
      when operating in the atmospheric environment. 

PMID- 25383298
TI  - Synthesis of Pt nanoparticles and their burrowing into Si due to synergistic
      effects of ion beam energy losses.
AB  - We report the synthesis of Pt nanoparticles and their burrowing into silicon upon
      irradiation of a Pt-Si thin film with medium-energy neon ions at constant fluence
      (1.0 * 10(17) ions/cm(2)). Several values of medium-energy neon ions were chosen
      in order to vary the ratio of the electronic energy loss to the nuclear energy
      loss (S e/S n) from 1 to 10. The irradiated films were characterized using
      Rutherford backscattering spectroscopy (RBS), atomic force microscopy (AFM),
      scanning electron microscopy (SEM), X-ray diffraction (XRD) and high resolution
      transmission electron microscopy (HRTEM). A TEM image of a cross section of the
      film irradiated with S e/S n = 1 shows ~5 nm Pt NPs were buried up to ~240 nm
      into the silicon. No silicide phase was detected in the XRD pattern of the film
      irradiated at the highest value of S e/S n. The synergistic effect of the energy
      losses of the ion beam (molten zones are produced by S e, and sputtering and
      local defects are produced by S n) leading to the synthesis and burrowing of Pt
      NPs is evidenced. The Pt NP synthesis mechanism and their burrowing into the
      silicon is discussed in detail. 

PMID- 25383299
TI  - Cathode lens spectromicroscopy: methodology and applications.
AB  - The implementation of imaging techniques with low-energy electrons at synchrotron
      laboratories allowed for significant advancement in the field of
      spectromicroscopy. The spectroscopic photoemission and low energy electron
      microscope, SPELEEM, is a notable example. We summarize the multitechnique
      capabilities of the SPELEEM instrument, reporting on the instrumental aspects and
      the latest developments on the technical side. We briefly review applications,
      which are grouped into two main scientific fields. The first one covers different
      aspects of graphene physics. In particular, we highlight the recent work on
      graphene/Ir(100). Here, SPELEEM was employed to monitor the changes in the
      electronic structure that occur for different film morphologies and during the
      intercalation of Au. The Au monolayer, which creeps under graphene from the film
      edges, efficiently decouples the graphene from the substrate lowering the Dirac
      energy from 0.42 eV to 0.1 eV. The second field combines magnetism studies at the
      mesoscopic length scale with self-organized systems featuring ordered
      nanostructures. This example highlights the possibility to monitor growth
      processes in real time and combine chemical characterization with X-ray magnetic
      circular dichroism-photoemission electron microscopy (XMCD-PEEM) magnetic imaging
      by using the variable photon polarization and energy available at the synchrotron
      source. 

PMID- 25383297
TI  - Carbon-based smart nanomaterials in biomedicine and neuroengineering.
AB  - The search for advanced biomimetic materials that are capable of offering a
      scaffold for biological tissues during regeneration or of electrically connecting
      artificial devices with cellular structures to restore damaged brain functions is
      at the forefront of interdisciplinary research in materials science. Bioactive
      nanoparticles for drug delivery, substrates for nerve regeneration and active
      guidance, as well as supramolecular architectures mimicking the extracellular
      environment to reduce inflammatory responses in brain implants, are within reach
      thanks to the advancements in nanotechnology. In particular, carbon-based
      nanostructured materials, such as graphene, carbon nanotubes (CNTs) and
      nanodiamonds (NDs), have demonstrated to be highly promising materials for
      designing and fabricating nanoelectrodes and substrates for cell growth, by
      virtue of their peerless optical, electrical, thermal, and mechanical properties.
      In this review we discuss the state-of-the-art in the applications of
      nanomaterials in biological and biomedical fields, with a particular emphasis on
      neuroengineering. 

PMID- 25383300
TI  - Spin annihilations of and spin sifters for transverse electric and transverse
      magnetic waves in co- and counter-rotations.
AB  - This study is motivated in part to better understand multiplexing in wireless
      communications, which employs photons carrying varying angular momenta. In
      particular, we examine both transverse electric (TE) and transverse magnetic (TM)
      waves in either co-rotations or counter-rotations. To this goal, we analyze both
      Poynting-vector flows and orbital and spin parts of the energy flow density for
      the combined fields. Consequently, we find not only enhancements but also
      cancellations between the two modes. To our surprise, the photon spins in the
      azimuthal direction exhibit a complete annihilation for the counter-rotational
      case even if the intensities of the colliding waves are of different magnitudes.
      In contrast, the orbital flow density disappears only if the two intensities
      satisfy a certain ratio. In addition, the concepts of spin sifters and enantiomer
      sorting are illustrated. 

PMID- 25383301
TI  - Dynamic calibration of higher eigenmode parameters of a cantilever in atomic
      force microscopy by using tip-surface interactions.
AB  - We present a theoretical framework for the dynamic calibration of the higher
      eigenmode parameters (stiffness and optical lever inverse responsivity) of a
      cantilever. The method is based on the tip-surface force reconstruction technique
      and does not require any prior knowledge of the eigenmode shape or the particular
      form of the tip-surface interaction. The calibration method proposed requires a
      single-point force measurement by using a multimodal drive and its accuracy is
      independent of the unknown physical amplitude of a higher eigenmode. 

PMID- 25383302
TI  - Imaging the intracellular degradation of biodegradable polymer nanoparticles.
AB  - In recent years, the development of smart drug delivery systems based on
      biodegradable polymeric nanoparticles has become of great interest. Drug-loaded
      nanoparticles can be introduced into the cell interior via endocytotic processes
      followed by the slow release of the drug due to degradation of the nanoparticle.
      In this work, poly(L-lactic acid) (PLLA) was chosen as the biodegradable polymer.
      Although common degradation of PLLA has been studied in various biological
      environments, intracellular degradation processes have been examined only to a
      very limited extent. PLLA nanoparticles with an average diameter of approximately
      120 nm were decorated with magnetite nanocrystals and introduced into mesenchymal
      stem cells (MSCs). The release of the magnetite particles from the surface of the
      PLLA nanoparticles during the intracellular residence was monitored by
      transmission electron microscopy (TEM) over a period of 14 days. It was
      demonstrated by the release of the magnetite nanocrystals from the PLLA surface
      that the PLLA nanoparticles do in fact undergo degradation within the cell.
      Furthermore, even after 14 days of residence, the PLLA nanoparticles were found
      in the MSCs. Additionally, the ultrastructural TEM examinations yield insight
      into the long term intercellular fate of these nanoparticles. From the
      statistical analysis of ultrastructural details (e.g., number of detached
      magnetite crystals, and the number of nanoparticles in one endosome), we
      demonstrate the importance of TEM studies for such applications in addition to
      fluorescence studies (flow cytometry and confocal laser scanning microscopy). 

PMID- 25383303
TI  - High speed e-beam lithography for gold nanoarray fabrication and use in
      nanotechnology.
AB  - E-beam lithography has been used for reliable and versatile fabrication of sub-15
      nm single-crystal gold nanoarrays and led to convincing applications in
      nanotechnology. However, so far this technique was either too slow for centimeter
      to wafer-scale writing or fast enough with the so-called dot on the fly (DOTF)
      technique but not optimized for sub-15 nm dots dimension. This prevents use of
      this technology for some applications and characterization techniques. Here, we
      show that the DOTF technique can be used without degradation in dots dimension.
      In addition, we propose two other techniques. The first one is an advanced
      conventional technique that goes five times faster than the conventional one. The
      second one relies on sequences defined before writing which enable versatility in
      e-beam patterns compared to the DOTF technique with same writing speed. By
      comparing the four different techniques, we evidence the limiting parameters for
      the writing speed. Wafer-scale fabrication of such arrays with 50 nm pitch
      allowed XPS analysis of a ferrocenylalkyl thiol self-assembled monolayer coated
      gold nanoarray. 

PMID- 25383304
TI  - Patterning a hydrogen-bonded molecular monolayer with a hand-controlled scanning
      probe microscope.
AB  - One of the paramount goals in nanotechnology is molecular-scale functional
      design, which includes arranging molecules into complex structures at will. The
      first steps towards this goal were made through the invention of the scanning
      probe microscope (SPM), which put single-atom and single-molecule manipulation
      into practice for the first time. Extending the controlled manipulation to larger
      molecules is expected to multiply the potential of engineered nanostructures.
      Here we report an enhancement of the SPM technique that makes the manipulation of
      large molecular adsorbates much more effective. By using a commercial motion
      tracking system, we couple the movements of an operator's hand to the sub
      angstrom precise positioning of an SPM tip. Literally moving the tip by hand we
      write a nanoscale structure in a monolayer of large molecules, thereby showing
      that our method allows for the successful execution of complex manipulation
      protocols even when the potential energy surface that governs the interaction
      behaviour of the manipulated nanoscale object(s) is largely unknown. 

PMID- 25383305
TI  - Towards bottom-up nanopatterning of Prussian blue analogues.
AB  - Ordered nanoperforated TiO2 monolayers fabricated through sol-gel chemistry were
      used to grow isolated particles of Prussian blue analogues (PBA). The elaboration
      of the TiO2/CoFe PBA nanocomposites involves five steps. The samples were
      characterized by scanning electron microscopy (SEM), atomic force microscopy
      (AFM), infrared spectroscopy and X-ray photoelectron spectroscopy (XPS) all along
      the synthesis process. Selected physico-chemical parameters have been varied in
      order to determine the key steps of the synthesis process and to optimize it.
      This study is an important step towards the full control of the fabrication
      process. 

PMID- 25383307
TI  - The impact of the confinement of reactants on the metal distribution in
      bimetallic nanoparticles synthesized in reverse micelles.
AB  - A kinetic study on the formation of bimetallic nanoparticles in microemulsions
      was carried out by computer simulation. A comprehensive analysis of the resulting
      nanostructures was performed regarding the influence of intermicellar exchange on
      reactivity. The objects of this study were metals having a difference in standard
      reduction potential of about 0.2-0.3 V. Relatively flexible microemulsions were
      employed and the concentration of the reactants was kept constant, while the
      reaction rate of each metal was monitored as a function of time using different
      reactant proportions. It was demonstrated that the reaction rates depend not only
      on the chemical reduction rate, but also on the intermicellar exchange rate.
      Furthermore, intermicellar exchange causes the accumulation of slower precursors
      inside the micelles, which favors chemical reduction. As a consequence, slower
      reduction rates strongly correlate with the number of reactants in this confined
      media. On the contrary, faster reduction rates are limited by the intermicellar
      exchange rate and not the number of reactants inside the micelles. As a result,
      different precursor proportions lead to different sequences of metal reduction,
      and thus the arrangement of the two metals in the nanostructure can be
      manipulated. 

PMID- 25383308
TI  - Carbon nano-onions (multi-layer fullerenes): chemistry and applications.
AB  - This review focuses on the development of multi-layer fullerenes, known as carbon
      nano-onions (CNOs). First, it briefly summarizes the most important synthetic
      pathways for their preparation and their properties and it gives the reader an
      update over new developments in the recent years. This is followed by a
      discussion of the published synthetic procedures for CNO functionalization, which
      are of major importance when elucidating future applications and addressing
      drawbacks for possible applications, such as poor solubility in common solvents.
      Finally, it gives an overview over the fields of application, in which CNO
      materials were successfully implemented. 

PMID- 25383309
TI  - Photodetectors based on carbon nanotubes deposited by using a spray technique on
      semi-insulating gallium arsenide.
AB  - In this paper, a spray technique is used to perform low temperature deposition of
      multi-wall carbon nanotubes on semi-insulating gallium arsenide in order to
      obtain photodectors. A dispersion of nanotube powder in non-polar 1,2
      dichloroethane is used as starting material. The morphological properties of the
      deposited films has been analysed by means of electron microscopy, in scanning
      and transmission mode. Detectors with different layouts have been prepared and
      current-voltage characteristics have been recorded in the dark and under
      irradiation with light in the range from ultraviolet to near infrared. The device
      spectral efficiency obtained from the electrical characterization is finally
      reported and an improvement of the photodetector behavior due to the nanotubes is
      presented and discussed. 

PMID- 25383310
TI  - Rapid degradation of zinc oxide nanoparticles by phosphate ions.
AB  - Zinc oxide nanoparticles are highly sensitive towards phosphate ions even at pH
      7. Buffer solutions and cell culture media containing phosphate ions are able to
      destroy ZnO nanoparticles within a time span from less than one hour to one day.
      The driving force of the reaction is the formation of zinc phosphate of very low
      solubility. The morphology of the zinc oxide particles has only a minor influence
      on the kinetics of this reaction. Surface properties related to different
      production methods and the presence and absence of labelling with a perylene
      fluorescent dye are more important. Particles prepared under acidic conditions
      are more resistant than those obtained in basic or neutral reaction medium.
      Surprisingly, the presence of a SiO2 coating does not impede the degradation of
      the ZnO core. In contrast to phosphate ions, beta-glycerophosphate does not
      damage the ZnO nanoparticles. These findings should be taken into account when
      assessing the biological effects or the toxicology of zinc oxide nanoparticles. 

PMID- 25383306
TI  - PVP-coated, negatively charged silver nanoparticles: A multi-center study of
      their physicochemical characteristics, cell culture and in vivo experiments.
AB  - PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a
      hydrodynamic diameter of 120 nm and a zeta potential of -20 mV were prepared and
      investigated with regard to their biological activity. This review summarizes the
      physicochemical properties (dissolution, protein adsorption, dispersability) of
      these nanoparticles and the cellular consequences of the exposure of a broad
      range of biological test systems to this defined type of silver nanoparticles.
      Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in
      biological media (i.e., in the presence of proteins) the surface of silver
      nanoparticles is rapidly coated by a protein corona that influences their
      physicochemical and biological properties including cellular uptake. Silver
      nanoparticles are taken up by cell-type specific endocytosis pathways as
      demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A
      visualization of particles inside cells is possible by X-ray microscopy,
      fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles,
      their localization inside the cell can be additionally determined. While primary
      brain astrocytes are shown to be fairly tolerant toward silver nanoparticles,
      silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and
      lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster
      fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver
      nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at
      rather high concentrations. The same was found in precision-cut lung slices of
      rats in which silver nanoparticles remained mainly at the tissue surface. In a
      human 3D triple-cell culture model consisting of three cell types (alveolar
      epithelial cells, macrophages, and dendritic cells), adverse effects were also
      only found at high silver concentrations. The silver ions that are released from
      silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds)
      and induce oxidative stress in skin cells (HaCaT). In conclusion, the data
      obtained on the effects of this well-defined type of silver nanoparticles on
      various biological systems clearly demonstrate that cell-type specific properties
      as well as experimental conditions determine the biocompatibility of and the
      cellular responses to an exposure with silver nanoparticles. 

PMID- 25383311
TI  - Effect of nano silver and silver nitrate on seed yield of (Ocimum basilicum L.).
AB  - BACKGROUND: The aim of this study was to evaluate the effect of nano silver and
      silver nitrate on yield of seed in basil plant. The study was carried out in a
      randomized block design with three replications. RESULTS: Four levels of either
      silver nitrate (0, 100, 200 and 300 ppm) or nano silver (0, 20, 40, and 60 ppm)
      were sprayed on basil plant at seed growth stage. The results showed that there
      was no significant difference between 100 ppm of silver nitrate and 60 ppm
      concentration of nano silver on the shoot silver concentration. However,
      increasing the concentration of silver nitrate from 100 to 300 ppm caused a
      decrease in seed yield. In contrast, a raise in the concentration of nano silver
      from 20 to 60 ppm has led to an improvement in the seed yield. Additionally, the
      lowest amount of seed yield was found with control plants. CONCLUSIONS: Finally,
      with increasing level of silver nitrate, the polyphenol compound content was
      raised but the enhancing level of nano silver resulting in the reduction of these
      components. In conclusion, nano silver can be used instead of other compounds of
      silver.

PMID- 25383312
TI  - First principles studies of electron tunneling in proteins.
AB  - A first principles study of electronic tunneling along the chain of seven Fe/S
      clusters in respiratory complex I, a key enzyme in the respiratory electron
      transport chain, is described. The broken-symmetry states of the Fe/S metal
      clusters calculated at both DFT and semi-empirical ZINDO levels were utilized to
      examine both the extremely weak electronic couplings between Fe/S clusters and
      the tunneling pathways, which provide a detailed atomistic-level description of
      the charge transfer process in the protein. One-electron tunneling approximation
      was found to hold within a reasonable accuracy, with only a moderate induced
      polarization of the core electrons. The method is demonstrated to be able to
      calculate accurately the coupling matrix elements as small as 10-4 cm-1. A
      distinct signature of the wave properties of electrons is observed as quantum
      interferences of multiple tunneling pathways.

PMID- 25383313
TI  - The di-peptide Trp-His activates AMP-activated protein kinase and enhances
      glucose uptake independently of insulin in L6 myotubes.
AB  - The di-peptide Trp-His (WH) has vasorelaxant and anti-atherosclerotic functions.
      We hypothesized that WH has multiple biological functions and may aid AMP
      activated protein kinase (AMPK) activation and affect the glucose transport
      system in skeletal muscle. First, we examined whether WH or His-Trp (HW) can
      activate AMPKalpha. Treatment of L6 myotubes with WH or HW significantly
      increased phosphorylation of AMPKalpha. WH activated AMPK independently of
      insulin and significantly increased glucose uptake into L6 myotubes following
      translocation of glucose transporter 4 (Glut4) to the plasma membrane. This
      activation was induced by the LKB1 pathway but was independent of changes in
      intracellular Ca(2+) levels and the Ca(2+)/calmodulin-dependent kinase pathway.
      L6 myotubes express only one type of oligopeptide transporter, peptide/histidine
      transporter 1 (PHT1, also known as SLC15a4), and WH is incorporated into cells
      and activates AMPKalpha following PHT1-mediated cell uptake. These findings
      indicate that (1) WH activates AMPK and insulin independently enhances glucose
      uptake following translocation of Glut4 to the plasma membrane, (2) activation of
      AMPKalpha by WH is mediated by the LKB1 pathway, without altering the Ca(2+)
      dependent pathway, and (3) L6 myotubes express only one type of peptide
      transporter (PHT1; SLC15a4), which incorporates WH into cells to activate
      AMPKalpha. 

PMID- 25383314
TI  - Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride
      accumulation in the mouse liver.
AB  - Although fasting induces hepatic triglyceride (TG) accumulation in both rodents
      and humans, little is known about the underlying mechanism. Because
      parasympathetic nervous system activity tends to attenuate the secretion of very
      low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the
      liver, and serum cholinesterase activity is elevated in fatty liver disease, the
      inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE)
      may have some influence on hepatic lipid metabolism. To assess the influence of
      AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE
      inhibitor, on fasting-induced increase in liver TG was investigated in mice. In
      comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation
      accompanied by a downregulation of sterol regulatory element-binding protein 1
      (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted
      the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner,
      accompanied by a significant fall in plasma insulin levels, without a fall in
      plasma TG. Furthermore, physostigmine significantly attenuated the fasting
      induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and
      increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist
      atropine blocked these effects of physostigmine on liver TG, serum insulin, and
      hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE
      inhibition facilitated fasting-induced TG accumulation with up regulation of the
      hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of
      muscarinic acetylcholine receptors. Our studies highlight the crucial role of
      parasympathetic regulation in fasting-induced TG accumulation, and may be an
      important source of information on the mechanism of hepatic disorders of lipid
      metabolism. 

PMID- 25383315
TI  - Update on the Pharmacological Treatment of Pathological Gambling.
AB  - This is an update to a previously published article discussing the
      neuropsychopharmacology of pathological gambling (PG) (1). In the prior
      manuscript, we described how cortico-limbic circuitry and neurotransmitter
      systems (norepinephrine, serotonin, dopamine, opioids, glutamate, and gamma
      aminobutyric acid (GABA)) have been implicated in PG. These systems represent
      potential targets for psychopharmacological treatments for PG, with opioid
      antagonists arguably showing the most consistent benefit in RCTs. In the past
      year and half since this publication was prepared, there has been one additional
      randomized clinical trial (RCT) published along with a single case study. Our
      original manuscript did not describe in detail findings from case studies or open
      label studies so in addition to the new RCT data and a new case report involving
      naltrexone, here we describe case and open-label findings. A PubMed search was
      conducted using terms such as "pathological gambling treatment", "clinical trials
      and gambling", and "gambling psychopharmacology." Using these search terms,
      numerous results were obtained, necessitating further search modifiers. For
      example, using just "pathological gambling treatment" results in over 1600 hits.
      In order to focus in on the search modalities, we searched within the initial
      results for specific phrases such as "psychopharmacology, clinical trial,
      medication, serotonergic, dopaminergic, etc." in addition to searching for
      specific medications. Results not directly related to the treatment of
      pathological gambling were not included. The study of pathological gambling is
      relatively new. As such, our search did not exclude any studies due to age of
      material, but with a few exceptions, the majority of the studies discussed were
      published later than 2000. This resulted in 24 case studies and/or RCTs not
      previously included in our original review article. These findings in conjunction
      with our prior publication provide a comprehensive overview of controlled
      investigations and exploratory reports of pharmacotherapies for PG.

PMID- 25383316
TI  - Successful therapy of progressive rhino-orbital mucormycosis caused by Rhizopus
      arrhizus with combined and sequential antifungal therapy, surgery and hyperbaric
      therapy.
AB  - We present a case of rhino-orbitary mucormycosis which progressed despite
      liposomal amphotericin and early surgical debridement. Combined echinocandin and
      high dose liposomal amphotericin, repeated debridement, prolonged therapy with
      hyperbaric oxygen and continued therapy with posaconazole, along with strict
      diabetic control, allowed cure without disfigurement. 

PMID- 25383317
TI  - Use of combination therapy to successfully treat breakthrough Trichosporon asahii
      infection in an acute leukemia patient receiving voriconazole.
AB  - Trichosporon species is an important life-threatening opportunistic systemic
      pathogen, especially in leukemia patients. Voriconazole is proved to be a
      promising agent in past decade. However, recently we observed a case of
      breakthrough Trichosporon asahii infection while receiving voriconazole, which
      calls for an alternative treatment strategy. A combination therapy of liposomal
      amphotericin B (AmB) plus caspofungin - in which liposomal AmB dose was reduced
      due to renal toxicity - was administered to successfully treat this patient. 

PMID- 25383318
TI  - Onychomycosis by Fusarium oxysporum probably acquired in utero.
AB  - Fusarium oxysporum has been described as a pathogen causing onychomycosis, its
      incidence has been increasing in immunocompetent and disseminated infection can
      occur in immunosuppressed individuals. We describe the first case of congenital
      onychomycosis in a child caused by Fusarium oxysporum. The infection being
      acquired in utero was proven by molecular methods with the identification of the
      fungus both in the nail and placenta, most probably as an ascending
      contamination/infection in a HIV-positive, immunosuppressed mother. 

PMID- 25383319
TI  - Functional neuroimaging abnormalities in idiopathic generalized epilepsy.
AB  - Magnetic resonance imaging (MRI) techniques have been used to quantitatively
      assess focal and network abnormalities. Idiopathic generalized epilepsy (IGE) is
      characterized by bilateral synchronous spike-wave discharges on
      electroencephalography (EEG) but normal clinical MRI. Dysfunctions involving the
      neocortex, particularly the prefrontal cortex, and thalamus likely contribute to
      seizure activity. To identify possible morphometric and functional differences in
      the brains of IGE patients and normal controls, we employed measures of thalamic
      volumes, cortical thickness, gray-white blurring, fractional anisotropy (FA)
      measures from diffusion tensor imaging (DTI) and fractional amplitude of low
      frequency fluctuations (fALFF) in thalamic subregions from resting state
      functional MRI. Data from 27 patients with IGE and 27 age- and sex-matched
      controls showed similar thalamic volumes, cortical thickness and gray-white
      contrast. There were no differences in FA values on DTI in tracts connecting the
      thalamus and prefrontal cortex. Functional analysis revealed decreased fALFF in
      the prefrontal cortex (PFC) subregion of the thalamus in patients with IGE. We
      provide minimum detectable effect sizes for each measure used in the study. Our
      analysis indicates that fMRI-based methods are more sensitive than quantitative
      structural techniques for characterizing brain abnormalities in IGE.

PMID- 25383320
TI  - Cystine nephrolithiasis.
AB  - Our understanding of the molecular basis of cystinuria has deepened as the result
      of the causative genes, SLC3A1 and SLC7A9, being identified. The proteins coded
      for by these genes form a heterodimer responsible for reabsorption of filtered
      cystine in the proximal tubule. Failure of this transport system to be targeted
      to the apical membrane, as in the case of SLC3A1 mutations, or failure of the
      transport system to function, as in the case of SLC7A9 mutations, leads to
      abnormal urinary excretion of the relatively insoluble amino acid cystine. Stones
      and plugs of tubules result, with chronic kidney disease a frequent complication.
      Here we review the genetics, pathophysiology, pathology, clinical manifestations
      and clinical management. Increased fluid intake, restriction of sodium and animal
      protein ingestion, and urinary alkalinization are the standard therapies. Cystine
      binding thiol drugs tiopronin and D-penicillamine are reserved for patients for
      whom the conservative therapies are insufficient. New studies of cystine crystal
      inhibition are highlighted.

PMID- 25383334
TI  - Ethical issues of transplanting organs from transgenic animals into human beings.
AB  - One of the most important applications of transgenic animals for medical purposes
      is to transplant their organs into human's body, an issue which has caused a lot
      of ethical and scientific discussions. we can divide the ethical arguments to two
      comprehensive groups; the first group which is known as deontological critiques
      (related to the action itself regardless of any results pointing the human or
      animal) and the second group, called the consequentialist critiques (which are
      directly pointing the consequences of the action). The latter arguments also can
      be divided to two subgroups. In the first one which named anthropocentrism, just
      humankind has inherent value in the moral society, and it studies the problem
      just from a human-based point of view while in second named, biocentrism all the
      living organism have this value and it deals specially with the problem from the
      animal-based viewpoint. In this descriptive-analytic study, ethical issues were
      retrieved from books, papers, international guidelines, thesis, declarations and
      instructions, and even some weekly journals using keywords related to transgenic
      animals, organ, and transplantation. According to the precautionary principle
      with the strong legal and ethical background, due to lack of accepted scientific
      certainties about the safety of the procedure, in this phase, transplanting
      animal's organs into human beings have the potential harm and danger for both
      human and animals, and application of this procedure is unethical until the
      safety to human will be proven. 

PMID- 25383339
TI  - Erratum: study of sperm reproductive parameters in mature zanjani viper.

PMID- 25383340
TI  - Celiac and Non-Celiac Forms of Gluten Sensitivity: Shifting Paradigms of an Old
      Disease.
AB  - Gluten sensitivity is one of the prominent features of celiac disease (CD) which
      is an autoimmune disorder characterized by damaged lining of the small intestine.
      CD was known already to ancient Greeks as
      kappaomicroniotalambdaiotaalphakappaomicronsigma (keeleeakoss) i.e. disease of
      the abdominal cavity hence celiac. Focus of this Commentary article is on rather
      complex definition of CD and its emerging new forms the example of which is non
      celiac gluten sensitivity. It is becoming evident that to formulate more
      effective treatments, these associations and newly identified disease entities
      deserve attention from both academic and clinical communities.

PMID- 25383321
TI  - Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis.
AB  - Calcium oxalate (CaOx) kidney stones are formed attached to Randall's plaques
      (RPs) or Randall's plugs. Mechanisms involved in the formation and growth are
      poorly understood. It is our hypothesis that stone formation is a form of
      pathological biomineralization or ectopic calcification. Pathological
      calcification and plaque formation in the body is triggered by reactive oxygen
      species (ROS) and the development of oxidative stress (OS). This review explores
      clinical and experimental data in support of ROS involvement in the formation of
      CaOx kidney stones. Under normal conditions the production of ROS is tightly
      controlled, increasing when and where needed. Results of clinical and
      experimental studies show that renal epithelial exposure to high oxalate and
      crystals of CaOx/calcium phosphate (CaP) generates excess ROS, causing injury and
      inflammation. Major markers of OS and inflammation are detectable in urine of
      stone patients as well as rats with experimentally induced CaOx nephrolithiasis.
      Antioxidant treatments reduce crystal and oxalate induced injury in tissue
      culture and animal models. Significantly lower serum levels of antioxidants,
      alpha-carotene, beta-carotene and beta-cryptoxanthine have been found in
      individuals with a history of kidney stones. A diet rich in antioxidants has been
      shown to reduce stone episodes. ROS regulate crystal formation, growth and
      retention through the timely production of crystallization modulators. In the
      presence of abnormal calcium, citrate, oxalate, and/or phosphate, however, there
      is an overproduction of ROS and a decrease in the antioxidant capacity resulting
      in OS, renal injury and inflammation. Cellular degradation products in the urine
      promote crystallization in the tubular lumen at a faster rate thus blocking the
      tubule and plugging the tubular openings at the papillary tips forming Randall's
      plugs. Renal epithelial cells lining the loops of Henle/collecting ducts may
      become osteogenic, producing membrane vesicles at the basal side. In addition
      endothelial cells lining the blood vessels may also become osteogenic producing
      membrane vesicles. Calcification of the vesicles gives rise to RPs. The growth of
      the RP's is sustained by mineralization of collagen laid down as result of
      inflammation and fibrosis.

PMID- 25383342
TI  - Surface microhardness of three thicknesses of mineral trioxide aggregate in
      different setting conditions.
AB  - OBJECTIVES: This study aimed to compare the surface microhardness of mineral
      trioxide aggregate (MTA) samples having different thicknesses and exposed to
      human blood from one side and with or without a moist cotton pellet on the other
      side. MATERIALS AND METHODS: Ninety cylindrical molds with three heights of 2, 4,
      and 6 mm were fabricated. In group 1 (dry condition), molds with heights of 2, 4,
      and 6 mm (10 molds of each) were filled with ProRoot MTA (Dentsply Tulsa Dental),
      and the upper surface of the material was not exposed to any additional moisture.
      In groups 2 and 3, a distilled water- or phosphate-buffered saline (PBS)
      moistened cotton pellet was placed on the upper side of MTA, respectively. The
      lower side of the molds in all the groups was in contact with human blood-wetted
      foams. After 4 day, the Vickers microhardness of the upper surface of MTA was
      measured. RESULTS: In the dry condition, the 4 and 6 mm-thick MTA samples showed
      significantly lower microhardness than the 2 mm-thick samples (p = 0.003 and p =
      0.001, respectively). However, when a distilled water- or PBS-moistened cotton
      pellet was placed over the MTA, no significant difference was found between the
      surface microhardness of samples having the abovementioned three thicknesses of
      the material (p = 0.210 and p = 0.112, respectively). CONCLUSIONS: It could be
      concluded that a moist cotton pellet must be placed over the 4 to 6 mm-thick MTA
      for better hydration of the material. However, this might not be necessary when 2
      mm-thick MTA is used.

PMID- 25383341
TI  - Antimicrobial effect of calcium hydroxide as an intracanal medicament in root
      canal treatment: a literature review - Part I. In vitro studies.
AB  - The goal of endodontic treatment is the prevention and control of pulpal and
      periradicular infections. Calcium hydroxide (Ca(OH)2) has been widely used in
      endodontics as an intracanal medicament to eliminate the remaining microorganisms
      after chemomechanical preparation. The purpose of this article is to review the
      antimicrobial properties of Ca(OH)2 as an intracanal medicament in root canal
      treatment. The first part of this review details the characteristics of Ca(OH)2
      and summarizes the results of in vitro studies related to its antimicrobial
      effect. The antimicrobial effect of Ca(OH)2 results from the release of hydroxyl
      ions when it comes into contact with aqueous fluids. Ca(OH)2 has a wide range of
      antimicrobial effects against common endodontic pathogens, but is less effective
      against Enterococcus faecalis and Candida albicans. The addition of vehicles or
      other agents might contribute to the antimicrobial effect of Ca(OH)2. 

PMID- 25383343
TI  - Microorganism penetration in dentinal tubules of instrumented and retreated root
      canal walls. In vitro SEM study.
AB  - OBJECTIVES: This in vitro study aimed to investigate the ability of Candida
      albicans (C. albicans) and Enterococcus faecalis (E. faecalis) to penetrate
      dentinal tubules of instrumented and retreated root canal surface of split human
      teeth. MATERIALS AND METHODS: Sixty intact extracted human single-rooted teeth
      were divided into 4 groups, negative control, positive control without canal
      instrumentation, instrumented, and retreated. Root canals in the instrumented
      group were enlarged with endodontic instruments, while root canals in the
      retreated group were enlarged, filled, and then removed the canal filling
      materials. The teeth were split longitudinally after canal preparation in 3
      groups except the negative control group. The teeth were inoculated with both
      microorganisms separately and in combination. Teeth specimens were examined by
      scanning electron microscopy (SEM), and the depth of penetration into the
      dentinal tubules was assessed using the SMILE view software (JEOL Ltd). RESULTS:
      Penetration of C. albicans and E. faecalis into the dentinal tubules was observed
      in all 3 groups, although penetration was partially restricted by dentin debris
      of tubules in the instrumented group and remnants of canal filling materials in
      the retreated group. In all 3 groups, E. faecalis penetrated deeper into the
      dentinal tubules by way of cell division than C. albicans which built colonies
      and penetrated by means of hyphae. CONCLUSIONS: Microorganisms can easily
      penetrate dentinal tubules of root canals with different appearance based on the
      microorganism size and status of dentinal tubules.

PMID- 25383344
TI  - Effect of ultrasonic tip designs on intraradicular post removal.
AB  - OBJECTIVES: To evaluate the effect of different ultrasonic tip designs on
      intraradicular post removal. MATERIALS AND METHODS: The crowns of forty human
      canine teeth were removed, and after biomechanical preparation and filling, the
      roots were embedded in acrylic resin blocks. The post spaces were made, and root
      canal molding was performed with self-cured acrylic resin. After casting (Cu-Al),
      the posts were cemented with zinc phosphate cement. The specimens were randomly
      separated into 4 groups (n = 10), as follows: G1 - no ultrasonic vibration
      (control); G2 - ultrasonic vibration using an elongated cylindrical-shaped and
      active rounded tip; G3 - ultrasonic vibration with a flattened convex and linear
      active tip; G4 - ultrasonic vibration with active semicircular tapered tip.
      Ultrasonic vibration was applied for 15 seconds on each post surface and tensile
      test was performed in a Universal Testing Machine (Instron 4444 - 1 mm/min).
      RESULTS: G4 presented the highest mean values, however, with no statistically
      significant difference in comparison to G3 (P > 0.05). G2 presented the lowest
      mean values with statistically significant difference to G3 and G4 (P < 0.05).
      CONCLUSIONS: Ultrasonic vibration with elongated cylindrical-shaped and active
      rounded tip was most effective in reducing force required for intraradicular post
      removal.

PMID- 25383345
TI  - Buckling resistance, bending stiffness, and torsional resistance of various
      instruments for canal exploration and glide path preparation.
AB  - OBJECTIVES: This study compared the mechanical properties of various instruments
      for canal exploration and glide-path preparations. MATERIALS AND METHODS: The
      buckling resistance, bending stiffness, ultimate torsional strength, and fracture
      angle under torsional load were compared for C+ file (CP, Dentsply Maillefer), M
      access K-file (MA, Dentsply Maillefer), Mani K-file (MN, Mani), and NiTiFlex K
      file (NT, Dentsply Maillefer). The files of ISO size #15 and a shaft length of 25
      mm were selected. For measuring buckling resistance (n = 10), the files were
      loaded in the axial direction of the shaft, and the maximum load was measured
      during the files' deflection. The files (n = 10) were fixed at 3-mm from the tip
      and then bent 45 degrees  with respect to their long axis, while the bending
      force was recorded by a load cell. For measuring the torsional properties, the
      files (n = 10) were also fixed at 3-mm, and clockwise rotations (2-rpm) were
      applied to the files in a straight state. The torsional load and the distortion
      angle were recorded until the files succumbed to the torque. RESULTS: The CP was
      shown to require the highest load to buckle and bend the files, and the NT showed
      the least. While MA and MN showed similar buckling resistances, MN showed higher
      bending stiffness than MA. The NT had the lowest bending stiffness and ultimate
      torsional strength (p < 0.05). CONCLUSIONS: The tested instruments showed
      different mechanical properties depending on the evaluated parameters. CP and NT
      files were revealed to be the stiffest and the most flexible instruments,
      respectively.

PMID- 25383346
TI  - Cutting efficiency of apical preparation using ultrasonic tips with
      microprojections: confocal laser scanning microscopy study.
AB  - OBJECTIVES: The purpose of this study was to compare the cutting efficiency of a
      newly developed microprojection tip and a diamond-coated tip under two different
      engine powers. MATERIALS AND METHODS: The apical 3-mm of each root was resected,
      and root-end preparation was performed with upward and downward pressure using
      one of the ultrasonic tips, KIS-1D (Obtura Spartan) or JT-5B (B&L Biotech Ltd.).
      The ultrasonic engine was set to power-1 or -4. Forty teeth were randomly divided
      into four groups: K1 (KIS-1D / Power-1), J1 (JT-5B / Power-1), K4 (KIS-1D / Power
      4), and J4 (JT-5B / Power-4). The total time required for root-end preparation
      was recorded. All teeth were resected and the apical parts were evaluated for the
      number and length of cracks using a confocal scanning micrscope. The size of the
      root-end cavity and the width of the remaining dentin were recorded. The data
      were statistically analyzed using two-way analysis of variance and a Mann-Whitney
      test. RESULTS: There was no significant difference in the time required between
      the instrument groups, but the power-4 groups showed reduced preparation time for
      both instrument groups (p < 0.05). The K4 and J4 groups with a power-4 showed a
      significantly higher crack formation and a longer crack irrespective of the
      instruments. There was no significant difference in the remaining dentin
      thickness or any of the parameters after preparation. CONCLUSIONS: Ultrasonic
      tips with microprojections would be an option to substitute for the conventional
      ultrasonic tips with a diamond coating with the same clinical efficiency.

PMID- 25383347
TI  - Push-out bond strength of a self-adhesive resin cement used as endodontic sealer.
AB  - OBJECTIVES: The aim of the present study was to investigate the bond strength of
      RelyX Unicem (3M) to root canal dentin when used as an endodontic sealer.
      MATERIALS AND METHODS: Samples of 24 single-rooted teeth were prepared with Gates
      Glidden drills and K3 files. After that, the roots were randomly assigned to
      three experimental groups (n = 8) according to the filling material, (1) AH Plus
      (Dentsply De Trey GmbH)/Gutta-Percha cone; (2) Epiphany SE (Pentron)/Resilon
      cone; (3) RelyX Unicem/Gutta-Percha cone. All roots were filled using a single
      cone technique associated to vertical condensation. After the filling procedures,
      each tooth was prepared for a push-out bond strenght test by cutting 1 mm-thick
      root slices. Loading was performed on a universal testing machine at a speed of
      0.5 mm/min. One-way analysis of variance and Tukey test for multiple comparisons
      were used to compare the results among the experimental groups. RESULTS: Epiphany
      SE/Resilon showed significantly lower push-out bond strength than both AH
      Plus/Gutta-Percha and RelyX Unicem/Gutta-Percha (p < 0.05). There was no
      significant difference in bond strength between AH Plus/Gutta-Percha and RelyX
      Unicem/Gutta-Percha (p > 0.05). CONCLUSIONS: Under the present in vitro
      conditions, bond strength to root dentin promoted by RelyX Unicem was similar to
      AH Plus. Epiphany SE/Resilon resulted in lower bond strength values when compared
      to both materials.

PMID- 25383348
TI  - Synergistic effect of xylitol and ursolic acid combination on oral biofilms.
AB  - OBJECTIVES: This study was designed to evaluate the synergistic antibacterial
      effect of xylitol and ursolic acid (UA) against oral biofilms in vitro. MATERIALS
      AND METHODS: S. mutans UA 159 (wild type), S. mutans KCOM 1207, KCOM 1128 and S.
      sobrinus ATCC 33478 were used. The susceptibility of S. mutans to UA and xylitol
      was evaluated using a broth microdilution method. Based on the results, combined
      susceptibility was evaluated using optimal inhibitory combinations (OIC), optimal
      bactericidal combinations (OBC), and fractional inhibitory concentrations (FIC).
      The anti-biofilm activity of xylitol and UA on Streptococcus spp. was evaluated
      by growing cells in 24-well polystyrene microtiter plates for the biofilm assay.
      Significant mean differences among experimental groups were determined by
      Fisher's Least Significant Difference (p < 0.05). RESULTS: The synergistic
      interactions between xylitol and UA were observed against all tested strains,
      showing the FICs < 1. The combined treatment of xylitol and UA inhibited the
      biofilm formation significantly and also prevented pH decline to critical value
      of 5.5 effectively. The biofilm disassembly was substantially influenced by
      different age of biofilm when exposed to the combined treatment of xylitol and
      UA. Comparing to the single strain, relatively higher concentration of xylitol
      and UA was needed for inhibiting and disassembling biofilm formed by a mixed
      culture of S. mutans 159 and S. sobrinus 33478. CONCLUSIONS: This study
      demonstrated that xylitol and UA, synergistic inhibitors, can be a potential
      agent for enhancing the antimicrobial and anti-biofilm efficacy against S. mutans
      and S. sobrinus in the oral environment.

PMID- 25383349
TI  - Bond strength of resin cement to CO2 and Er:YAG laser-treated zirconia ceramic.
AB  - OBJECTIVES: It is difficult to achieve adhesion between resin cement and zirconia
      ceramics using routine surface preparation methods. The aim of this study was to
      evaluate the effects of CO2 and Er:YAG laser treatment on the bond strength of
      resin cement to zirconia ceramics. MATERIALS AND METHODS: In this in-vitro study
      45 zirconia disks (6 mm in diameter and 2 mm in thickness) were assigned to 3
      groups (n = 15). In control group (CNT) no laser treatment was used. In groups
      COL and EYL, CO2 and Er:YAG lasers were used for pretreatment of zirconia
      surface, respectively. Composite resin disks were cemented on zirconia disk using
      dual-curing resin cement. Shear bond strength tests were performed at a crosshead
      speed of 0.5 mm/min after 24 hr distilled water storage. Data were analyzed by
      one-way ANOVA and post hoc Tukey's HSD tests. RESULTS: The means and standard
      deviations of shear bond strength values in the EYL, COL and CNT groups were 8.65
      +/- 1.75, 12.12 +/- 3.02, and 5.97 +/- 1.14 MPa, respectively. Data showed that
      application of CO2 and Er:YAG lasers resulted in a significant higher shear bond
      strength of resin cement to zirconia ceramics (p < 0.0001). The highest bond
      strength was recorded in the COL group (p < 0.0001). In the CNT group all the
      failures were adhesive. However, in the laser groups, 80% of the failures were of
      the adhesive type. CONCLUSIONS: Pretreatment of zirconia ceramic via CO2 and
      Er:YAG laser improves the bond strength of resin cement to zirconia ceramic, with
      higher bond strength values in the CO2 laser treated samples.

PMID- 25383350
TI  - Effect of antioxidants on push-out bond strength of hydrogen peroxide treated
      glass fiber posts bonded with two types of resin cement.
AB  - OBJECTIVES: Hydrogen peroxide (H2O2) surface treatment of fiber posts has been
      reported to increase bond strength of fiber posts to resin cements. However,
      residual oxygen radicals might jeopardize the bonding procedure. This study
      examined the effect of three antioxidant agents on the bond strength of fiber
      posts to conventional and self-adhesive resin cements. MATERIALS AND METHODS:
      Post spaces were prepared in forty human maxillary second premolars. Posts were
      divided into five groups of 8 each: G1 (control), no pre-treatment; G2, 10% H2O2
      pre-treatment; G3, G4 and G5. After H2O2 application, Hesperidin (HES), Sodium
      Ascorbate (SA) or Rosmarinic acid (RA) was applied on each group respectively. In
      each group four posts were cemented with Duo-Link conventional resin cement and
      the others with self-adhesive BisCem cement. Push-out test was performed and data
      were analyzed using 2-way ANOVA and tukey's post-hoc test (alpha = 0.05).
      RESULTS: There was a statistically significant interaction between the cement
      type and post surface treatment on push-out bond strength of fiber posts (p <
      0.001, F = 16). Also it was shown that different posts' surface treatments
      significantly affect the push-out bond strength of fiber posts (p = 0.001). H2O2
      treated posts (G2) and control posts (G1) cemented with Duo-link showed the
      highest (15.96 +/- 5.07MPa) and lowest bond strengths (6.79 +/- 3.94)
      respectively. CONCLUSIONS: It was concluded that H2O2 surface treatment might
      enhance the bond strength of fiber posts cemented with conventional resin
      cements. The effect of antioxidants as post's surface treatment agents depends on
      the characteristics of resin cements used for bonding procedure.

PMID- 25383351
TI  - The effect of resin thickness on polymerization characteristics of silorane-based
      composite resin.
AB  - OBJECTIVES: This study examined the influence of the resin thickness on the
      polymerization of silorane- and methacrylate-based composites. MATERIALS AND
      METHODS: One silorane-based (Filtek P90, 3M ESPE) and two methacrylate-based
      (Filtek Z250 and Z350, 3M ESPE) composite resins were used. The number of photons
      were detected using a photodiode detector at the different thicknesses
      (thickness, 1, 2 and 3 mm) specimens. The microhardness of the top and bottom
      surfaces was measured (n = 15) using a Vickers hardness with 200 gf load and 15
      sec dwell time conditions. The degree of conversion (DC) of the specimens was
      determined using Fourier transform infrared spectroscopy (FTIR). Scratched powder
      of each top and bottom surface of the specimen dissolved in ethanol for
      transmission FTIR spectroscopy. The refractive index was measured using a Abbe
      type refractometer. To measure the polymerization shrinkage, a linometer was
      used. The results were analyzed using two-way ANOVA and Tukey's test at p < 0.05
      level. RESULTS: The silorane-based resin composite showed the lowest filler
      content and light attenuation among the specimens. P90 showed the highest values
      in the DC and the lowest microhardness at all depth. In the polymerization
      shrinkage, P90 showed a significantly lower shrinkage than the rest two resin
      products (p < 0.05). P90 showed a significantly lower refractive index than the
      remaining two resin products (p < 0.05). CONCLUSIONS: DC, microhardness,
      polymerization rate and refractive index linearly decreased as specimen thickness
      linearly increased. P90 showed much less polymerization shrinkage compared to
      other specimens. P90, even though achieved the highest DC, showed the lowest
      microhardness and refractive index.

PMID- 25383352
TI  - Clinical management of a fused upper premolar with supernumerary tooth: a case
      report.
AB  - In dentistry, the term 'fusion' is used to describe a developmental disorder of
      dental hard tissues. In the permanent dentition, fusion of a normal tooth and a
      supernumerary tooth usually involves the incisors or canines. However, a few
      cases of fusion involving premolars have also been reported to date. We present a
      rare case in which fusion of the maxillary left second premolar and a
      supernumerary tooth in a 13-year-old girl was diagnosed using cone beam computed
      tomography (CBCT, Alphard-3030, Asahi Roentgen Ind. Co., Ltd.). The tooth was
      bicuspidized after routine nonsurgical root canal treatment, and the separated
      teeth underwent appropriate restoration procedures. The second premolar and
      supernumerary tooth remained asymptomatic without any signs of inflammation after
      a follow-up period of 9 years. Identification of anatomical anomalies is
      important for treatment in cases involving fusion with supernumerary tooth, and
      therefore the microscopic examinations and CBCT are essential for the diagnosis.
      Fused teeth can be effectively managed by the comprehensive treatment which
      includes both endodontic and periodontal procedures. 

PMID- 25383353
TI  - Reattachment of a fractured fragment with relined fiber post using indirect
      technique: a case report.
AB  - Although fiber-reinforced posts have been widely used, they sometimes fail to
      obtain sufficient retention because of an extremely large canal space. To address
      this, several techniques have been introduced including relining of the fiber
      reinforced posts. Here, we used a relined glass-fiber post to increase retention
      and fitness to the root canal in a crown reattachment case. The relining
      procedure was performed by using an indirect method on the working cast. This
      case also highlights the esthetic concerns regarding dehydration of the attached
      crown fragment. 

PMID- 25383354
TI  - Statistical notes for clinical researchers: Nonparametric statistical methods: 2.
      Nonparametric methods for comparing three or more groups and repeated measures.

PMID- 25383355
TI  - Zirconia surface treatment for successful bonding.

PMID- 25383356
TI  - NEIGHBORHOOD PERCEPTION AND OBESITY IN AGED MEXICAN AMERICANS.
AB  - BACKGROUND: Hypotheses on the relationship between neighborhood perception and
      obesity (as measured by body mass index) seem to generally posit that a positive
      neighborhood perception may be related with behaviors that positively moderate
      body weight. OBJECTIVE: To determine if and how there is an association between
      positive neighborhood perception and obesity-while accounting for frailty- and
      disability-related factors. DESIGN: Cross-sectional study from Wave-5 of the
      Hispanic Established Population for the Epidemiological Study of the Elderly
      (HEPESE). SETTING: Data files housed by the Sociomedical Division in the
      department of Community Health and Preventive Medicine at the University of Texas
      Medical Branch in Galveston, Texas. PARTICIPANTS: A total of 889, aged 75-90
      community-dwelling Mexican Americans in the Southwest United States.
      MEASUREMENTS: Body mass index (BMI=Kg/m(2)), neighborhood perception, grip
      strength, gait speed, depression symptomatology, chronic conditions, presence of
      limitations with basic and instrumental basic activities of daily living (ADLs),
      and other health and demographic variables are used in logistic regressions
      predicting the likelihood of being obese (BMI > 30 Kg/m(2)) versus being of
      normal weight (BMI 18.5-25.4 Kg/m(2)). RESULTS: The odds of being obese increase:
      as the level of positive neighborhood perception increases; grip strength
      increases; and with having any limitations with basic-ADLs. CONCLUSIONS: These
      findings provide evidence that a positive neighborhood perception need not always
      be accompanied with a reduced risk of being obese. Because functional limitations
      in older ages may influence how positive neighborhood perception affects BMI,
      more research is needed.

PMID- 25383357
TI  - Smokeless Tobacco Risk Comparison and Other Debate Messages in the News.
AB  - OBJECTIVES: Public health professionals have debated the use of smokeless tobacco
      (SLT) over cigarettes for harm reduction. This article describes SLT and
      cigarette risk comparisons and other SLT "debate" messages potentially reaching
      the public through news stories. METHODS: We conducted a content analysis of SLT
      related 2006-10 articles from top newspapers and selected news wires. RESULTS:
      About 16% of articles (N = 677) referred to SLT as less harmful than smoking,
      attributing these messages to public health professionals as frequently as to
      tobacco company representatives. About 29% of articles included an "anti" SLT
      message, including variously phrased warnings that SLT is not a safe smoking
      alternative, or other potential consequences such as youth uptake. CONCLUSION:
      Professionals should begin developing and using more consistent messages about
      SLT's risks.

PMID- 25383358
TI  - Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1
      Integrase Mutant Viruses.
AB  - Controlling the specificity of retroviral DNA integration could improve the
      safety of gene therapy vectors, and fusions of heterologous chromatin binding
      modules to the integrase-binding domain from the lentiviral integration host
      cofactor LEDGF/p75 are a promising retargeting strategy. We previously proposed
      the utility of integrase mutant lentiviral vectors that are selectively activated
      by complementary LEDGF/p75 variants, and our initial modifications in HIV-1
      integrase and LEDGF/p75 supported about 13% of wild-type vector transduction
      activity. Here we describe the selection and characterization of the K42E gain-of
      function mutation in HIV-1 integrase, which greatly improves the efficiency of
      this system. Both K42E and initial reverse-charge mutations in integrase
      negatively impacted reverse transcription and integration, yet when combined
      together boosted viral transduction efficiency to ~75% of the wild-type vector in
      a manner dependent on a complementary LEDGF/p75 variant. Although the K42E
      mutation conferred functional gains to integrase mutant viral reverse
      transcription and integration, only the integration boost depended on the
      engineered LEDGF/p75 mutant. We conclude that the specificity of lentiviral
      retargeting strategies based on heterologous LEDGF/p75 fusion proteins will
      benefit from our optimized system that utilizes the unique complementation
      properties of reverse-charge integrase mutant viral and LEDGF/p75 host proteins.

PMID- 25383359
TI  - Adipose tissue insulin receptor knockdown via a new primate-derived hybrid
      recombinant AAV serotype.
AB  - Adipose tissue plays an essential role in metabolic homeostasis, and holds
      promise as an alternative depot organ in gene therapy. However, efficient methods
      of gene transfer into adipose tissue in vivo have yet to be established. Here we
      assessed the transduction efficiency to fat depots by a family of novel
      engineered hybrid capsid serotypes (Rec1~4) recombinant AAV vectors in comparison
      with natural serotypes AAV1, AAV8, and AAV9. Rec2 serotype led to widespread
      transduction in both brown fat and white fat with the highest efficiency among
      the seven serotypes tested. As a proof-of-efficacy, Rec2 serotype was used to
      deliver Cre recombinase to adipose tissues of insulin receptor floxed animals.
      Insulin receptor knockdown led to decreased fat pad mass, morphological and
      molecular changes in the targeted depot. These novel hybrid AAV vectors can serve
      as powerful tools to genetically manipulate adipose tissue and provide valuable
      vehicles to gene therapy targeting adipose tissue.

PMID- 25383360
TI  - Indian jujuba seed powder as an eco-friendly and a low-cost biosorbent for
      removal of acid blue 25 from aqueous solution.
AB  - Indian jujuba seed powder (IJSP) has been investigated as a low-cost and an eco
      friendly biosorbent, prepared for the removal of Acid Blue 25 (AB25) from aqueous
      solution. The prepared biomaterial was characterized by using FTIR and scanning
      electron microscopic studies. The effect of operation variables, such as IJSP
      dosage, contact time, concentration, pH, and temperature on the removal of AB25
      was investigated, using batch biosorption technique. Removal efficiency increased
      with increase of IJSP dosage but decreased with increase of temperature. The
      equilibrium data were analyzed by the Langmuir and the Freundlich isotherm
      models. The data fitted well with the Langmuir model with a maximum biosorption
      capacity of 54.95 mg g(-1). The pseudo-second-order kinetics was the best for the
      biosorption of AB25 by IJSP, with good correlation. Thermodynamic parameters such
      as standard free energy change (DeltaG(0)), standard enthalpy changes
      (DeltaH(0)), and standard entropy changes (DeltaS(0)) were analyzed. The removal
      of AB25 from aqueous solution by IJSP was a spontaneous and exothermic adsorption
      process. The results suggest that IJSP is a potential low-cost and an eco
      friendly biosorbent for the AB25 removal from synthetic AB25 wastewater.

PMID- 25383361
TI  - Thermodynamic modeling of hydrogen storage capacity in Mg-Na alloys.
AB  - Thermodynamic modeling of the H-Mg-Na system is performed for the first time in
      this work in order to understand the phase relationships in this system. A new
      thermodynamic description of the stable NaMgH3 hydride is performed and the
      thermodynamic models for the H-Mg, Mg-Na, and H-Na systems are reassessed using
      the modified quasichemical model for the liquid phase. The thermodynamic
      properties of the ternary system are estimated from the models of the binary
      systems and the ternary compound using CALPHAD technique. The constructed
      database is successfully used to reproduce the pressure-composition isotherms for
      MgH2 + 10 wt.% NaH mixtures. Also, the pressure-temperature equilibrium diagram
      and reaction paths for the same composition are predicted at different
      temperatures and pressures. Even though it is proved that H-Mg-Na does not meet
      the DOE hydrogen storage requirements for onboard applications, the best working
      temperatures and pressures to benefit from its full catalytic role are given.
      Also, the present database can be used for thermodynamic assessments of higher
      order systems.

PMID- 25383362
TI  - sexual shape dimorphism of the mangrove crab Ucides cordatus (Linnaeus, 1763)
      (Decapoda, Ucididae) accessed through geometric morphometric.
AB  - Sexual dimorphism is often observed in Crustaceans. Considering the great
      diversity of this subphylum, only few reports are found in the literature and
      most are mainly based on traditional morphometry. The present study uses
      geometric morphometrics analysis to identify sexual dimorphism by shape variation
      in the overexploited semiterrestrial crab Ucides cordatus, species with great
      social and economic importance in South America. Comparative morphology analyses
      were performed by using the outer face of the propodus of major cheliped, dorsal
      and anterior region of carapace shape. Significant differences in shape between
      sexes were detected in these body areas. The causes of dimorphism presented in
      this species are not clear but, analogous to other possibly associated species,
      it may be inferred that the causes are with adaptations to body ability of
      reproductive potential (females), and of reproductive behaviour and agonistics
      encounters (males). Additional analyses on courtship displays and other
      reproductive aspects should provide better comprehension of functionality of this
      morphological differentiation. 

PMID- 25383363
TI  - Floristic diversity and distribution pattern of plant communities along
      altitudinal gradient in Sangla Valley, Northwest Himalaya.
AB  - Himalayas are globally important biodiversity hotspots and are facing rapid loss
      in floristic diversity and changing pattern of vegetation due to various biotic
      and abiotic factors. This has necessitated the qualitative and quantitative
      assessment of vegetation here. The present study was conducted in Sangla Valley
      of northwest Himalaya aiming to assess the structure of vegetation and its trend
      in the valley along the altitudinal gradient. In the forest and alpine zones of
      the valley, 15 communities were recorded. Study revealed 320 species belonging to
      199 genera and 75 families. Asteraceae, Rosaceae, Apiaceae, and Ranunculaceae
      were dominant. Among genera, Artemisia followed by Polygonum, Saussurea,
      Berberis, and Thalictrum were dominant. Tree and shrub's density ranged from 205
      to 600 and from 105 to 1030 individual per hectare, respectively, whereas herbs
      ranged from 22.08 to 78.95 individual/m(2). Nearly 182 species were native to the
      Himalaya. Maximum altitudinal distribution of few selected climate sensitive
      species was found to be highest in northeast and north aspects. This study gives
      an insight into the floristic diversity and community structure of the fragile
      Sangla Valley which was hitherto not available. 

PMID- 25383364
TI  - Microwave irradiation of nanohydroxyapatite from chicken eggshells and duck
      eggshells.
AB  - Due to similarity in composition to the mineral component of bones and human hard
      tissues, hydroxyapatite with chemical formula Ca10(PO4)6(OH)2 has been widely
      used in medical field. Both chicken and duck eggshells are mainly composed of
      calcium carbonate. An attempt has been made to fabricate nanohydroxyapatite (nHA)
      by chicken (CES) and duck eggshells (DES) as calcium carbonate source (CaCO3).
      CES and DES were reacted with diammonium hydrogen [(NH4)2HPO4] solution and
      subjected to microwave heating at 15 mins. Under the effect of microwave
      irradiation, nHA was produced directly in the solution and involved in
      crystallographic transformation. Sample characterization was done using by X-ray
      diffraction (XRD), fourier transform infrared spectroscopy (FTIR), and scanning
      electron microscopy (SEM).

PMID- 25383365
TI  - Conjugates of a photoactivated rhodamine with biopolymers for cell staining.
AB  - Conjugates of the photoactivated rhodamine dyes with biopolymers (proteins,
      polysaccharides, and nucleic acids) are important tools for microscopic
      investigation of biological tissue. In this study, a precursor of the
      photoactivated fluorescent dye (PFD) has been successfully used for staining of
      numerous mammalian cells lines and for conjugate formation with chitosan
      ("Chitosan-PFD") and histone H1 ("Histone H1.3-PFD"). The intensive fluorescence
      has been observed after photoactivation of these conjugates inside cells (A431,
      HaCaT, HEK239, HBL-100, and MDCK). Developed procedures and obtained data are
      important for further application of novel precursors of fluorescent dyes
      ("caged" dyes) for microscopic probing of biological objects. Thus, the
      synthesized "Chitosan-PFD" and "Histone H1-PFD" have been successfully applied in
      this study for intracellular transport visualization by fluorescent microscopy. 

PMID- 25383366
TI  - Second and secondary lattice modules.
AB  - Let M be a lattice module over the multiplicative lattice L. A nonzero L-lattice
      module M is called second if for each a ? L, a1M = 1M or a1M = 0M . A nonzero L
      lattice module M is called secondary if for each a ? L, a1M = 1M or a(n)1M = 0 M
      for some n > 0. Our objective is to investigative properties of second and
      secondary lattice modules.

PMID- 25383367
TI  - Intravenous flat-detector computed tomography angiography for symptomatic
      cerebral vasospasm following aneurysmal subarachnoid hemorrhage.
AB  - The study evaluated the diagnostic accuracy of intravenous flat-detector computed
      tomography (IV FDCT) angiography in assessing hemodynamically significant
      cerebral vasospasm in patients with subarachnoid hemorrhage (SAH) with digital
      subtraction angiography (DSA) as the reference. DSA and IV FDCT were conducted
      concurrently in patients suspected of having symptomatic cerebral vasospasm
      postoperatively. The presence and severity of vasospasm were estimated according
      to location (proximal versus distal). Vasospasm >50% was defined as having
      hemodynamic significance. Vasospasms <30% were excluded from this analysis to
      avoid spectrum bias. Twenty-nine patients (311 vessel segments) were measured.
      The intra- and interobserver agreements were excellent for depicting vasospasm (k
      = 0.84 and 0.74, resp.). IV FDCT showed a sensitivity of 95.7%, specificity of
      92.3%, positive predictive value of 93.6%, and negative predictive value of 94.7%
      for detecting vasospasm (>50%) with DSA as the reference. Bland-Altman plots
      revealed good agreement of assessing vasospasm between the two tests. The
      discrepancy of vasospasm severity was more noted in the distal location with high
      severity. However, it was not statistically significant (Spearman's rank test; r
      = 0.15, P = 0.35). Therefore, IV FDCT could be a feasible noninvasive test to
      evaluate suspected significant vasospasm in SAH. 

PMID- 25383368
TI  - Treatment of dentinal hypersensitivity by means of Nd:YAP Laser: a preliminary in
      vitro study.
AB  - OBJECTIVE: The aim of this study is to evaluate the effectiveness of Nd:YAP laser
      to seal dentinal tubules at different parameters. MATERIAL AND METHODS: 24 caries
      free human wisdom impacted molars were used. The crowns were sectioned
      transversally in order to totally expose the dentin. The smear layer was removed
      by a 1 min application of EDTA. Each surface was divided into four quadrants, but
      only three quadrants were irradiated at a different output power setting
      (irradiation speed: 1 mm/sec; optical fiber diameter: 320 um; tangential
      incidence of beam and in noncontact mode). Samples were smeared with a graphite
      paste prior to laser irradiation. All specimens were sent for SEM analysis. Pulp
      temperature increases in additional twenty teeth were measured by a thermocouple.
      RESULTS: Morphological changes in dentin surfaces depend on the value of used
      energy density. Higher energy densities (2 W-4 W; 200-400 mJ; pulse duration: 100
      m sec.; and 10 Hz) induce higher dentin modifications. Our results confirmed that
      Nd:YAP laser irradiations can lead to total or partial occlusion of dentin
      tubules without provoking fissures or cracks. Measurements of pulp temperature
      increases showed that Nd:YAP laser beam can be considered as harmless for pulp
      vitality for following irradiation conditions: 2 W (200 mJ) to 4 W (400 mJ) with
      an irradiation speed of 1 mm/sec; fiber diameter: 320 micrometers; 10 Hz; pulse
      duration: 100 m sec; noncontact mode and in tangential incidence to exposed
      dentin. The perpendicular incidence of the laser beam on exposed dentin may
      injure pulp vitality even at low output power of 3 W. CONCLUSIONS: Nd:YAP laser
      beam was able to seal the dentin tubules without damaging dentinal surfaces and
      without harming pulp vitality. Nd:YAP laser is effective and may be safely used
      for future in vivo treatments of dentinal hypersensitivity under certain
      conditions.

PMID- 25383369
TI  - Treatment efficacy of electromyography versus fiberscopy-guided botulinum toxin
      injection in adductor spasmodic dysphonia patients: a prospective comparative
      study.
AB  - INTRODUCTION: This study prospectively evaluates and compares the treatment
      efficacy of botulinum toxin injection under electromyography guidance (EMG group)
      and percutaneous botulinum toxin injection under flexible fiberscopic guidance
      (fiberscopy group). METHODS: Thirty patients with adductor spasmodic dysphonia
      (ADSD), who had never received treatment, were randomly allocated into EMG- or
      fiberscopy-guided botulinum toxin injections between March 2008 and February
      2010. We assessed acoustic and aerodynamic voice parameters, and the voice
      handicap index (VHI) before injection and at 1, 3, and 6 months after injection.
      RESULTS: The mean total dosage of botulinum toxin was similar for both groups:
      1.7 +/- 0.5 U for the EMG group and 1.8 +/- 0.4 U for the fiberscopy group (P >
      0.05). There were no significant differences in outcomes between the two groups
      in either the duration of effectiveness or complications such as breathy voice
      and aspiration. CONCLUSION: Botulinum toxin injection under fiberscopic guidance
      is a viable alternative to EMG-guided botulinum toxin injection for the treatment
      of adductor spasmodic dysphonia when EMG equipment is unavailable.

PMID- 25383370
TI  - Removal of endobronchial malignant mass by cryotherapy improved performance
      status to receive chemotherapy.
AB  - Although malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is
      reportedly a palliative treatment. Clinical data on postcryotherapy MEM patients
      in a university-affiliated hospital between 2007 and 2011 were evaluated.
      Survival curve with or without postcryotherapy chemotherapy and performance
      status (PS) improvement of these subjects were analyzed using the Kaplan-Meier
      method. There were 59 patients (42 males), with median age of 64 years (range, 51
      76, and median performance status of 2 (interquartile range [IQR], 2-3).
      Postcryotherapy complications included minor bleeding (n = 12) and need for
      multiple procedures (n = 10), while outcomes were relief of symptoms (n = 51),
      improved PS (n = 45), and ability to receive chemotherapy (n = 40). The survival
      of patients with chemotherapy postcryotherapy was longer than that of patients
      without such chemotherapy (median, 534 versus 106 days; log-rank test, P = 0.007;
      hazard ratio, 0.25; 95% confidence interval, 0.10-0.69). The survival of patients
      with PS improvement postcryotherapy was longer than that of patients without PS
      improvement (median, 406 versus 106 days; log-rank test, P = 0.02; hazard ratio,
      0.28; 95% confidence interval, 0.10-0.81). Cryotherapy is a feasible treatment
      for MEM. With better PS after cryotherapy, further chemotherapy becomes possible
      for patients to improve survival when MEM caused dyspnea and poor PS. 

PMID- 25383371
TI  - Dietary hyaluronic acid migrates into the skin of rats.
AB  - Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The
      oral intake of hyaluronic acid increases water in the horny layer as demonstrated
      by human trials, but in vivo kinetics has not been shown. This study confirmed
      the absorption, migration, and excretion of (14)C-labeled hyaluronic acid ((14)C
      hyaluronic acid). (14)C-hyaluronic acid was orally or intravenously administered
      to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration
      showed the highest level 8 hours after administration, and orally administered
      (14)C-hyaluronic acid was found in the blood. Approximately 90% of (14)C
      hyaluronic acid was absorbed from the digestive tract and used as an energy
      source or a structural constituent of tissues based on tests of the urine, feces,
      expired air, and cadaver up to 168 hours (one week) after administration. The
      autoradiographic results suggested that radioactivity was distributed
      systematically and then reduced over time. The radioactivity was higher in the
      skin than in the blood at 24 and 96 hours after administration. The results show
      the possibility that orally administered hyaluronic acid migrated into the skin.
      No excessive accumulation was observed and more than 90% of the hyaluronic acid
      was excreted in expired air or urine. 

PMID- 25383372
TI  - Toxocara (Nematoda: Ascaridida) and other soil-transmitted helminth eggs
      contaminating soils in selected urban and rural areas in the Philippines.
AB  - The extent of contamination of soils with soil transmitted helminthes (STH) eggs,
      particularly Toxocara, was determined in selected urban and rural towns of
      Laguna, Philippines. Soil samples were collected from public schools, house
      yards, and empty lots. Results revealed that, of the 1480 soil samples collected,
      460 (31%) were positive for STH eggs. Toxocara sp. was the most prevalent (77%),
      followed by Ascaris sp. (11%), hookworms/strongyles/free-living nematodes (7%),
      and Trichuris sp. (5%). Some soil physicochemical parameters were also determined
      and associated with Toxocara eggs prevalence and density in soil. Results
      revealed that Toxocara sp. eggs were most prevalent in less acidic, relatively
      high temperature and high moisture soil conditions. They were also prevalent in
      sandy, silty, and loamy soil textures but less prevalent in clayey. No
      significant differences were found between depth 1 (0-5 cm) and depth 2 (6-10
      cm). This study revealed that Toxocara sp. eggs are ubiquitous and the extent of
      contamination in soils from the selected towns of Laguna is relatively high.
      Hence, the data generated in this study can be used in promoting public
      awareness, particularly for pet owners and local health officials, for effective
      prevention and control of this parasitosis.

PMID- 25383373
TI  - Isolation of salt stress-related genes from Aspergillus glaucus CCHA by random
      overexpression in Escherichia coli.
AB  - The halotolerant fungus Aspergillus glaucus CCHA was isolated from the surface of
      wild vegetation around a saltern with the salinity range being 0-31%. Here, a
      full-length cDNA library of A. glaucus under salt stress was constructed to
      identify genes related to salt tolerance, and one hundred clones were randomly
      selected for sequencing and bioinformatics analysis. Among these, 82 putative
      sequences were functionally annotated as being involved in signal transduction,
      osmolyte synthesis and transport, or regulation of transcription. Subsequently,
      the cDNA library was transformed into E. coli cells to screen for putative salt
      stress-related clones. Five putative positive clones were obtained from E. coli
      cells grown on LB agar containing 1 M NaCl, on which they showed rapid growth
      compared to the empty vector control line. Analysis of transgenic Arabidopsis
      thaliana lines overexpressing CCHA-2142 demonstrated that the gene conferred
      increased salt tolerance to plants as well by protecting the cellular membranes,
      suppressing the inhibition of chlorophyll biosynthesis. These results highlight
      the utility of this A. glaucus cDNA library as a tool for isolating and
      characterizing genes related to salt tolerance. Furthermore, the identified genes
      can be used for the study of the underlying biology of halotolerance.

PMID- 25383374
TI  - Family support and loneliness among older persons in multiethnic Malaysia.
AB  - This study investigates factors affecting older persons' state of loneliness in
      multiethnic Malaysia using data from the 2004 Malaysian Population and Family
      Survey, the first nationally representative sample in Malaysia. The study sample
      was extracted to include Malays, Chinese, Indians and other Indigenous groups
      aged 60 and above, and who had children (n = 1791). Cross tabulations and ordinal
      logistic regression methods were used in the analysis. Among the ethnic groups,
      older Malays were more likely than their Chinese and Indian counterparts to
      experience loneliness. Loneliness was found to be associated with age, marital
      status, education level, sources of income, health status, and physical
      limitations. Among older people, feelings of loneliness were inversely related
      with coresidence with adult children and participation in religious activities.
      Sociodemographic changes have eroded the traditional family support system for
      the elderly, while social security remains inadequate. This study shows the
      important role of family in alleviating loneliness among older people. Hence the
      need to promote and facilitate coresidence, as well as participation in religious
      activities, and a healthy lifestyle as a priority strategy is in line with the
      objectives of the National Policy for the Older People. 

PMID- 25383375
TI  - Diuretic activity of the aqueous extract leaves of Ficus glumosa Del. (Moraceae)
      in rats.
AB  - Experiments were carried out to validate the use of F. glumosa extract as a
      diuretic in the treatment of hypertension as claimed by traditional healers. The
      experiments were performed under the same conditions with two synthetic
      pharmacological diuretics considered as check (Furosemide and Amiloride
      hydrochlorothiazide). The aqueous extract leaves of F. glumosa accelerated the
      elimination of overloaded fluid. At the maximum of diuretic response, urinary
      osmolarity decreased significantly when compared with controls. The single dose
      treatment of the aqueous extract leaves of F. glumosa has significantly increased
      urine volume 24 h after administration of the extract. The stability of
      aldosterone level, the absence of correlation with the plasma levels of sodium,
      and the increased clearance of free water in the animals receiving the extract
      show that increased diuresis and natriuresis moderate elevation are tubular in
      origin. The increase in Na(+), K(+), and Cl(-) induced by the extract caused
      alkalinization of the urine and showed a strong inhibitory effect of carbonic
      anhydrase and saluretic. These effects were mainly observed at the dose of 375
      mg/kg. These observations confirm the traditional use in the treatment of
      hypertension and support the importance of the conservation of local knowledge as
      well as the conservation of Cameroonian biodiversity.

PMID- 25383376
TI  - Multiparametric monitoring of early response to antiangiogenic therapy: a
      sequential perfusion CT and PET/CT study in a rabbit VX2 tumor model.
AB  - OBJECTIVES: To perform dual analysis of tumor perfusion and glucose metabolism
      using perfusion CT and FDG-PET/CT for the purpose of monitoring the early
      response to bevacizumab therapy in rabbit VX2 tumor models and to assess added
      value of FDG-PET to perfusion CT. METHODS: Twenty-four VX2 carcinoma tumors
      implanted in bilateral back muscles of 12 rabbits were evaluated. Serial
      concurrent perfusion CT and FDG-PET/CT were performed before and 3, 7, and 14
      days after bevacizumab therapy (treatment group) or saline infusion (control
      group). Perfusion CT was analyzed to calculate blood flow (BF), blood volume
      (BV), and permeability surface area product (PS); FDG-PET was analyzed to
      calculate SUVmax, SUVmean, total lesion glycolysis (TLG), entropy, and
      homogeneity. The flow-metabolic ratio (FMR) was also calculated and
      immunohistochemical analysis of microvessel density (MVD) was performed. RESULTS:
      On day 14, BF and BV in the treatment group were significantly lower than in the
      control group. There were no significant differences in all FDG-PET-derived
      parameters between both groups. In the treatment group, FMR prominently decreased
      after therapy and was positively correlated with MVD. CONCLUSIONS: In VX2 tumors,
      FMR could provide further insight into the early antiangiogenic effect reflecting
      a mismatch in intratumor blood flow and metabolism.

PMID- 25383377
TI  - Development and characterization of novel site specific hollow floating
      microspheres bearing 5-Fu for stomach targeting.
AB  - Multiple-unit-type oral floating hollow microspheres of 5-fluorouracil (5-Fu)
      were developed using modified solvent evaporation technique to prolong gastric
      residence time, to target stomach cancer, and to increase drug bioavailability.
      The prepared microspheres were characterized for micromeritic properties,
      floating behavior, entrapment efficiency, and scanning electron microscopy (SEM).
      The in vitro drug release and floating behavior were studied in simulated gastric
      fluid (SGF) at pH 1.2. The yield of microspheres was obtained up to 84.46 +/-
      6.47%. Microspheres showed passable flow properties. Based on optical microscopy,
      particle size was found to be ranging from 158.65 +/- 12.02 to 198.67 +/- 17.45
      MUm. SEM confirmed spherical size, perforated smooth surface, and a hollow cavity
      inside the microspheres. Different kinetic models for drug release were also
      applied on selected batches.

PMID- 25383378
TI  - Bioactivity of root endophytic freshwater Hyphomycetes Anguillospora longissima
      (Sacc. & Syd.) Ingold.
AB  - Anguillospora longissima, isolated from root as endophytic freshwater
      hyphomycetes, was evaluated for its bioactivity (antibacterial potential) against
      five bacterial strains, namely, Gram-positive (Bacillus subtilis MTCC 121) and
      Gram-negative (Agrobacterium tumefaciens MTCC 609, Escherichia coli MTCC 40,
      Erwinia chrysanthemum, and Xanthomonas pseudomonas). Antimicrobial activity was
      assessed by measuring the zone of inhibition with preliminary and secondary
      antimicrobial assays. The applied fungus was found significant for all tested
      bacterial strains as showen by their zone of inhibition. In preliminary
      antimicrobial assay, maximum zone of inhibition was recorded against Gram
      negative human pathogenic bacterial strain Escherichia coli (23 mm) followed by
      Erwinia chrysanthemi (22 mm), Agrobacterium tumefaciens (21 mm), and Xanthomonas
      phaseoli (21 mm), while minimum zone of inhibition was observed against Bacillus
      subtilis (20 mm). In secondary antimicrobial assay, the maximum zone of
      inhibition was recorded against Erwinia chrysanthemi (11 mm) followed by
      Agrobacterium tumefaciens (10 mm), Xanthomonas phaseoli (10 mm), and Bacillus
      subtilis (9 mm) and minimum inhibition was found against Escherichia coli (8 mm).

PMID- 25383379
TI  - Work-related health disorders among Saudi computer users.
AB  - The present study was conducted to investigate the prevalence of musculoskeletal
      disorders and eye and vision complaints among the computer users of King
      Abdulaziz University (KAU), Saudi Arabian Airlines (SAUDIA), and Saudi Telecom
      Company (STC). Stratified random samples of the work stations and operators at
      each of the studied institutions were selected and the ergonomics of the work
      stations were assessed and the operators' health complaints were investigated.
      The average ergonomic score of the studied work station at STC, KAU, and SAUDIA
      was 81.5%, 73.3%, and 70.3, respectively. Most of the examined operators use
      computers daily for <= 7 hours, yet they had some average incidences of general
      complaints (e.g., headache, body fatigue, and lack of concentration) and
      relatively high level of incidences of eye and vision complaints and
      musculoskeletal complaints. The incidences of the complaints have been found to
      increase with the (a) decrease in work station ergonomic score, (b) progress of
      age and duration of employment, (c) smoking, (d) use of computers, (e) lack of
      work satisfaction, and (f) history of operators' previous ailments. It has been
      recommended to improve the ergonomics of the work stations, set up training
      programs, and conduct preplacement and periodical examinations for operators. 

PMID- 25383380
TI  - Titanium dioxide as a catalyst support in heterogeneous catalysis.
AB  - The lack of stability is a challenge for most heterogeneous catalysts. During
      operations, the agglomeration of particles may block the active sites of the
      catalyst, which is believed to contribute to its instability. Recently, titanium
      oxide (TiO2) was introduced as an alternative support material for heterogeneous
      catalyst due to the effect of its high surface area stabilizing the catalysts in
      its mesoporous structure. TiO2 supported metal catalysts have attracted interest
      due to TiO2 nanoparticles high activity for various reduction and oxidation
      reactions at low pressures and temperatures. Furthermore, TiO2 was found to be a
      good metal oxide catalyst support due to the strong metal support interaction,
      chemical stability, and acid-base property. The aforementioned properties make
      heterogeneous TiO2 supported catalysts show a high potential in photocatalyst
      related applications, electrodes for wet solar cells, synthesis of fine
      chemicals, and others. This review focuses on TiO2 as a support material for
      heterogeneous catalysts and its potential applications. 

PMID- 25383381
TI  - Modeling of millimeter-wave modulation characteristics of semiconductor lasers
      under strong optical feedback.
AB  - This paper presents modeling and simulation on the characteristics of
      semiconductor laser modulated within a strong optical feedback (OFB-)induced
      photon-photon resonance over a passband of millimeter (mm) frequencies.
      Continuous wave (CW) operation of the laser under strong OFB is required to
      achieve the photon-photon resonance in the mm-wave band. The simulated time
      domain characteristics of modulation include the waveforms of the intensity and
      frequency chirp as well as the associated distortions of the modulated mm-wave
      signal. The frequency domain characteristics include the intensity modulation
      (IM) and frequency modulation (FM) responses in addition to the associated
      relative intensity noise (RIN). The signal characteristics under modulations with
      both single and two mm-frequencies are considered. The harmonic distortion and
      the third order intermodulation distortion (IMD3) are examined and the spurious
      free dynamic range (SFDR) is calculated. 

PMID- 25383383
TI  - Comparative evaluation of biomass power generation systems in China using hybrid
      life cycle inventory analysis.
AB  - There has been a rapid growth in using agricultural residues as an energy source
      to generate electricity in China. Biomass power generation (BPG) systems may vary
      significantly in technology, scale, and feedstock and consequently in their
      performances. A comparative evaluation of five typical BPG systems has been
      conducted in this study through a hybrid life cycle inventory (LCI) approach.
      Results show that requirements of fossil energy savings, and greenhouse gas (GHG)
      emission reductions, as well as emission reductions of SO2 and NOx, can be best
      met by the BPG systems. The cofiring systems were found to behave better than the
      biomass-only fired system and the biomass gasification systems in terms of energy
      savings and GHG emission reductions. Comparing with results of conventional
      process-base LCI, an important aspect to note is the significant contribution of
      infrastructure, equipment, and maintenance of the plant, which require the input
      of various types of materials, fuels, services, and the consequent GHG emissions.
      The results demonstrate characteristics and differences of BPG systems and help
      identify critical opportunities for biomass power development in China.

PMID- 25383382
TI  - Radiolabeled apoptosis imaging agents for early detection of response to therapy.
AB  - Since apoptosis plays an important role in maintaining homeostasis and is
      associated with responses to therapy, molecular imaging of apoptotic cells could
      be useful for early detection of therapeutic effects, particularly in oncology.
      Radiolabeled annexin V compounds are the hallmark in apoptosis imaging in vivo.
      These compounds are reviewed from the genesis of apoptosis (cell death) imaging
      agents up to recent years. They have some disadvantages, including slow clearance
      and immunogenicity, because they are protein-based imaging agents. For this
      reason, several studies have been conducted in recent years to develop low
      molecule apoptosis imaging agents. In this review, radiolabeled
      phosphatidylserine targeted peptides, radiolabeled bis(zinc(II)-dipicolylamine)
      complex, radiolabeled 5-fluoropentyl-2-methyl-malonic acid (ML-10), caspase-3
      activity imaging agents, radiolabeled duramycin, and radiolabeled phosphonium
      cation are reviewed as promising low-molecular-weight apoptosis imaging agents. 

PMID- 25383384
TI  - Pulp revascularization of immature permanent teeth: a review of the literature
      and a proposal of a new clinical protocol.
AB  - Tissue engineering is a growing field. In the near future, it will probably be
      possible to generate a complete vital tooth from a single stem cell. Pulp
      revascularization is dependent on the ability of residual pulp and apical and
      periodontal stem cells to differentiate. These cells have the ability to generate
      a highly vascularized and a conjunctive rich living tissue. This one is able to
      colonize the available pulp space. Revascularization is a new treatment method
      for immature necrotic permanent teeth. Up to now, apexification procedures were
      applied for these teeth, using calcium dihydroxide or MTA to produce an
      artificial apical barrier. However, the pulp revascularization allows the
      stimulation of the apical development and the root maturation of immature teeth.
      Two pulp revascularization techniques are used in the literature, one using
      calcium dihydroxide and the second using a triple antibiotic paste. Based on
      these two different pulp revascularization protocols, which obtain the desired
      therapeutic success, the literature will be reviewed and analyzed according to
      the relevance of their choice of materials. Based on the literature, we propose a
      new relevant protocol and a new mixture of antibiotics. 

PMID- 25383385
TI  - Oral crest lengthening for increasing removable denture retention by means of CO2
      laser.
AB  - The loss of teeth and their replacement by artificial denture is associated with
      many problems. The denture needs a certain amount of ridge height to give it
      retention and a long-term function. Crest lengthening procedures are performed to
      provide a better anatomic environment and to create proper supporting structures
      for more stability and retention of the denture. The purpose of our study is to
      describe and evaluate the effectiveness of CO2 laser-assisted surgery in patients
      treated for crest lengthening (vestibular deepening). There have been various
      surgical techniques described in order to restore alveolar ridge height by
      pushing muscles attaching of the jaws. Most of these techniques cause
      postoperative complications such as edemas, hemorrhage, pain, infection, slow
      healing, and rebound to initial position. Our clinical study describes the
      treatment planning and clinical steps for the crest lengthening with the use of
      CO2 laser beam (6-15 Watts in noncontact, energy density range: 84.92-212.31
      J/cm(2), focus, and continuous mode with a focal point diameter of 0.3 mm). At
      the end of each surgery, dentures were temporarily relined with a soft material.
      Patients were asked to mandatorily wear their relined denture for a minimum of 4
      6 weeks and to remove it for hygienic purposes. At the end of each surgery, the
      deepest length of the vestibule was measured by the operator. No sutures were
      made and bloodless wounds healed in second intention without grafts. Results
      pointed out the efficiency of the procedure using CO2 laser. At 8 weeks of post
      op, the mean of crest lengthening was stable without rebound. Only a loss of 15%
      was noticed. To conclude, the use of CO2 laser is an effective option for crest
      lengthening.

PMID- 25383386
TI  - The impact of a submaximal level of exercise on balance performance in older
      persons.
AB  - OBJECTIVE: The purpose of this study was to determine the impact of a submaximal
      level of exercise on balance performance under a variety of conditions. MATERIAL
      AND METHOD: Thirteen community-dwelling older persons with intact foot sensation
      (age = 66.69 +/- 8.17 years, BMI = 24.65 +/- 4.08 kg/m(2), female, n = 6)
      volunteered to participate. Subjects' balance performances were measured using
      the Modified Clinical Test of Sensory Integration of Balance (mCTSIB) at baseline
      and after test, under four conditions of stance: (1) eyes-opened firm-surface
      (EOF), (2) eyes-closed firm-surface (ECF), (3) eyes-opened soft-surface (EOS),
      and (4) eyes-closed soft-surface (ECS). The 6-minute walk test (6MWT) protocol
      was used to induce the submaximal level of exercise. Data was analyzed using the
      Wilcoxon Signed-Rank Test. RESULTS: Balance changes during EOF (z = 0.00, P =
      1.00) and ECF (z = -1.342, P = 0.180) were not significant. However, balance
      changes during EOS (z = -2.314, P = 0.021) and ECS (z = -3.089, P = 0.02) were
      significantly dropped after the 6MWT. CONCLUSION: A submaximal level of exercise
      may influence sensory integration that in turn affects balance performance,
      particularly on an unstable surface. Rehabilitation should focus on designing
      intervention that may improve sensory integration among older individuals with
      balance deterioration in order to encourage functional activities.

PMID- 25383387
TI  - Delirium management in critically ill patients.
AB  - Delirium among critically ill patients is common. Presence of delirium imparts a
      poorer prognosis to patients, including longer ICU and hospital length of stay,
      increased risk of institutionalization, higher health related costs, and elevated
      mortality. Even with such grave consequences, the rates of delirium diagnosis are
      dire. The importance of early recognition through validated tools and appropriate
      management of this life-threatening condition cannot be over emphasized. This
      article provides an overview of delirium pathophysiology, diagnosis, and
      management with a focus on critically ill patients.

PMID- 25383389
TI  - DATA CLEANING: LONGITUDINAL STUDY CROSS-VISIT CHECKS.
AB  - Cross-visit checks are a vital part of data cleaning for longitudinal studies.
      The nature of longitudinal studies encourages repeatedly collecting the same
      information. Sometimes, these variables are expected to remain static, go away,
      increase, or decrease over time. This presentation reviews the naive and the
      better approaches at handling one-variable and two-variable consistency checks.
      For a single-variable check, the better approach features the new ALLCOMB
      function, introduced in SAS(r) 9.2. For a two-variable check, the better approach
      uses a BY PROCESSING variable to flag inconsistencies. This paper will provide
      you the tools to enhance your longitudinal data cleaning process.

PMID- 25383388
TI  - Deletion of Virus-specific T-cells Enhances Remyelination in a Model of Multiple
      Sclerosis.
AB  - We used transgenic expression of capsid antigens to Theiler's murine
      encephalomyelitis virus (TMEV) to study how the immune response to VP1 and VP2
      influences spinal cord demyelination, remyelination and axonal loss during the
      acute and chronic phases of infection. Expression from birth of capsid antigen
      under the ubiquitin promoter resulted in tolerance to the antigen and absence of
      an immune response to the respective capsid antigen following virus infection.
      The transgenic mice were crossed to B10.Q mice normally susceptible to
      demyelination but which, when compared to FVB mice of the same H2 q haplotype,
      show poor remyelination. The major finding in this study was that VP1+ and VP2+
      animals featured more remyelination at all three chronic time points (90, 180 and
      270 dpi) than transgene-negative controls. Interestingly, at 270 dpi,
      remyelination in VP1+ mice tended to be higher and more complete than that in
      VP2+ mice. Compared with transgene- negative controls, VP1+ and VP2+ animals
      showed similar demyelination in but less only late in the disease (270 dpi). The
      number of mid-thoracic axons at the last time point correlated with the levels of
      remyelination. The increase in number of axons in VP1+ mice with remyelination
      was driven by counts in medium- and large-caliber axons. This study supports the
      hypothesis that expression of viral capsid proteins as self and subsequent
      genetic deletion of capsid-specific T cells influences the extent of spinal cord
      remyelination following Theiler's virus-induced demyelination. We propose that
      VP1- and, to a lesser extent, VP2-specific CD8+ T cells limit and/or prevent the
      naturally occurring process of remyelination. This finding may have relevance to
      human multiple sclerosis, as targeted removal of CD8+ T cells specific for a yet
      to-be-discovered causative peptide may enhance remyelination and prevent axonal
      loss in patients.

PMID- 25383390
TI  - Uncertainty Visualization in Forward and Inverse Cardiac Models.
AB  - Quantification and visualization of uncertainty in cardiac forward and inverse
      problems with complex geometries is subject to various challenges. Specific to
      visualization is the observation that occlusion and clutter obscure important
      regions of interest, making visual assessment difficult. In order to overcome
      these limitations in uncertainty visualization, we have developed and implemented
      a collection of novel approaches. To highlight the utility of these techniques,
      we evaluated the uncertainty associated with two examples of modeling myocardial
      activity. In one case we studied cardiac potentials during the repolarization
      phase as a function of variability in tissue conductivities of the ischemic heart
      (forward case). In a second case, we evaluated uncertainty in reconstructed
      activation times on the epicardium resulting from variation in the control
      parameter of Tikhonov regularization (inverse case). To overcome difficulties
      associated with uncertainty visualization, we implemented linked-view windows and
      interactive animation to the two respective cases. Through dimensionality
      reduction and superimposed mean and standard deviation measures over time, we
      were able to display key features in large ensembles of data and highlight
      regions of interest where larger uncertainties exist.

PMID- 25383391
TI  - PARP1 gene variation and microglial activity on [11C]PBR28 PET in older adults at
      risk for Alzheimer's disease.
AB  - Increasing evidence suggests that inflammation is one pathophysio-logical
      mechanism in Alzheimer's disease (AD). Recent studies have identifiedan
      association between the poly (ADP-ribose) polymerase 1 (PARP1) gene and AD. This
      gene encodes a protein that is involved in many biological functions, including
      DNA repair and chromatin remodeling, and is a mediator of inflammation.
      Therefore, we performed a targeted genetic association analysis to investigate
      the relationship between the PARP1 polymorphisms and brain micro-glial activity
      as indexed by [11C]PBR28 positron emission tomography (PET). Participants were 26
      non-Hispanic Caucasians in the Indiana Memory and Aging Study (IMAS). PET data
      were intensity-normalized by injected dose/total body weight. Average PBR
      standardized uptake values (SUV) from 6 bilateral regions of interest (thalamus,
      frontal, parietal, temporal, and cingulate cortices, and whole brain gray matter)
      were used as endophenotypes. Single nucleotide polymorphisms (SNPs) with 20%
      minor allele frequency that were within +/- 20 kb of the PARP1 gene were included
      in the analyses. Gene-level association analyses were performed using a dominant
      genetic model with translocator protein (18-kDa) (TSPO) genotype, age at PET
      scan, and gender as covariates. Analyses were performed with and without APOE
      epsilon4 status as a covariate. Associations with PBR SUVs from thalamus and
      cingulate were significant at corrected p<0.014 and <0.065, respectively.
      Subsequent multi-marker analysis with cingulate PBR SUV showed that individuals
      with the "C" allele at rs6677172 and "A" allele at rs61835377 had higher PBR SUV
      than individuals without these alleles (corrected P<0.03), and individuals with
      the "G" allele at rs6677172 and "G" allele at rs61835377 displayed the opposite
      trend (corrected P<0.065). A previous study with the same cohort showed an
      inverse relationship between PBR SUV and brain atrophy at a follow-up visit,
      suggesting possible protective effect of microglial activity against cortical
      atrophy. Interestingly, all 6 AD and 2 of 3 LMCI participants in the current
      analysis had one or more copies of the "GG" allele combination, associated with
      lower cingulate PBR SUV, suggesting that this gene variant warrants further
      investigation.

PMID- 25383392
TI  - A Graph-Based Integration of Multimodal Brain Imaging Data for the Detection of
      Early Mild Cognitive Impairment (E-MCI).
AB  - Alzheimer's disease (AD) is the most common cause of dementia in older adults. By
      the time an individual has been diagnosed with AD, it may be too late for
      potential disease modifying therapy to strongly influence outcome. Therefore, it
      is critical to develop better diagnostic tools that can recognize AD at early
      symptomatic and especially pre-symptomatic stages. Mild cognitive impairment
      (MCI), introduced to describe a prodromal stage of AD, is presently classified
      into early and late stages (E-MCI, L-MCI) based on severity. Using a graph-based
      semi-supervised learning (SSL) method to integrate multimodal brain imaging data
      and select valid imaging-based predictors for optimizing prediction accuracy, we
      developed a model to differentiate E-MCI from healthy controls (HC) for early
      detection of AD. Multimodal brain imaging scans (MRI and PET) of 174 E-MCI and 98
      HC participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI)
      cohort were used in this analysis. Mean targeted region-of-interest (ROI) values
      extracted from structural MRI (voxel-based morphometry (VBM) and FreeSurfer V5)
      and PET (FDG and Florbetapir) scans were used as features. Our results show that
      the graph-based SSL classifiers outperformed support vector machines for this
      task and the best performance was obtained with 66.8% cross-validated AUC (area
      under the ROC curve) when FDG and FreeSurfer datasets were integrated. Valid
      imaging-based phenotypes selected from our approach included ROI values extracted
      from temporal lobe, hippocampus, and amygdala. Employing a graph-based SSL
      approach with multimodal brain imaging data appears to have substantial potential
      for detecting E-MCI for early detection of prodromal AD warranting further
      investigation.

PMID- 25383393
TI  - Deformation field correction for spatial normalization of PET images using a
      population-derived partial least squares model.
AB  - Spatial normalization of positron emission tomography (PET) images is essential
      for population studies, yet work on anatomically accurate PET-to-PET registration
      is limited. We present a method for the spatial normalization of PET images that
      improves their anatomical alignment based on a deformation correction model
      learned from structural image registration. To generate the model, we first
      create a population-based PET template with a corresponding structural image
      template. We register each PET image onto the PET template using deformable
      registration that consists of an affine step followed by a diffeomorphic mapping.
      Constraining the affine step to be the same as that obtained from the PET
      registration, we find the diffeomorphic mapping that will align the structural
      image with the structural template. We train partial least squares (PLS)
      regression models within small neighborhoods to relate the PET intensities and
      deformation fields obtained from the diffeomorphic mapping to the structural
      image deformation fields. The trained model can then be used to obtain more
      accurate registration of PET images to the PET template without the use of a
      structural image. A cross validation based evaluation on 79 subjects shows that
      our method yields more accurate alignment of the PET images compared to
      deformable PET-to-PET registration as revealed by 1) a visual examination of the
      deformed images, 2) a smaller error in the deformation fields, and 3) a greater
      overlap of the deformed anatomical labels with ground truth segmentations.

PMID- 25383394
TI  - Subject Specific Sparse Dictionary Learning for Atlas based Brain MRI
      Segmentation.
AB  - Quantitative measurements from segmentations of soft tissues from magnetic
      resonance images (MRI) of human brains provide important biomarkers for normal
      aging, as well as disease progression. In this paper, we propose a patch-based
      tissue classification method from MR images using sparse dictionary learning from
      an atlas. Unlike most atlas-based classification methods, deformable registration
      from the atlas to the subject is not required. An "atlas" consists of an MR
      image, its tissue probabilities, and the hard segmentation. The "subject"
      consists of the MR image and the corresponding affine registered atlas
      probabilities (or priors). A subject specific patch dictionary is created by
      learning relevant patches from the atlas. Then the subject patches are modeled as
      sparse combinations of learned atlas patches. The same sparse combination is
      applied to the segmentation patches of the atlas to generate tissue memberships
      of the subject. The novel combination of prior probabilities in the example
      patches enables us to distinguish tissues having similar intensities but having
      different spatial location. We show that our method outperforms two state-of-the
      art whole brain tissue segmentation methods. We experimented on 12 subjects
      having manual tissue delineations, obtaining mean Dice coefficients of 0:91 and
      0:87 for cortical gray matter and cerebral white matter, respectively. In
      addition, experiments on subjects with ventriculomegaly shows significantly
      better segmentation using our approach than the competing methods.

PMID- 25383395
TI  - Providing Culturally Appropriate Education on Type 2 Diabetes to Rural American
      Indians: Emotions and Racial Consciousness.
AB  - Healthy and balanced emotions are an important aspect of well-being. Today,
      diabetes has a high prevalence in American Indian communities. Four Talking
      Circle facilitators were interviewed in a phenomenological research study to
      describe their experience of facilitating Talking Circles during a diabetes
      research intervention, Diabetes Wellness: American Indian Talking Circles. The
      Diabetes Wellness study provided a twelve week educational curriculum in a
      Talking Circle format to target prevention and effective maintenance of symptoms
      of Type 2 diabetes among American Indians adults on two rural Northern Plains
      reservations. Seven essential themes emerged from the phenomenological study
      data. This report describes one theme: expression of the emotional aspect of
      diabetes and three sub-themes that depict American Indian culture: connectedness,
      collective living, and transformation. Type 2 diabetes is a chronic disease that
      affects the emotional status of American Indians in rural communities. The notion
      of racial consciousness is discussed as a potential context from which Talking
      Circle facilitators can operate and Talking Circle participants respond. This
      viewpoint may be a useful cultural approach for lay personnel with an (emic)
      inside perspective like Talking Circle facilitators when working in areas like
      rural American Indian reservations.

PMID- 25383396
TI  - Mohs micrographic surgery for basal cell carcinomas: results of a Spanish
      retrospective study and Kaplan-Meier survival analysis of tumour recurrence.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) is a specialized procedure usually
      limited to specific indications (e.g. high-risk basal cell carcinomas [BCCs]).
      OBJECTIVE: To determine the recurrence rate of MMS for BCC at a tertiary referral
      centre in Barcelona, Spain. METHODS: Review of medical records of patients
      undergoing 534 consecutive MMS interventions for confirmed BCCs. The main outcome
      measure was biopsy-proven recurrence of BCC at the same anatomical location after
      MMS. RESULTS: A total of 489 patients underwent MMS for 534 BCCs from April 1999
      to December 2011. The patients' mean age was 66 years. The most frequent location
      was the nasal/perinasal region (38.4%, n = 205). The surgical interventions of
      47.9% (n = 256) were for primary BCCs and 52.1% (n = 278) procedures were for
      recurrent or residual BCCs. The mean follow-up was 30.5 months (range 1-145
      months). Thirty-two recurrences were identified in total. The raw recurrence rate
      following MMS for primary BCCs was 1.2% (3/256) compared to 10.4% (32/278) for
      recurrent BCC. On multivariate analysis (Cox proportional hazard model) only
      prior treatment (P = 0.018, hazard ratio [HR] 4.68 with 95% confidence intervals
      [CI] 1.30-16.79), multiple prior treatments (P = 0.013, HR 2.72 [95%CI 1.24
      5.96]), and healing by secondary intention (P = 0.041, HR 2.88 [95%CI 1.04-7.97])
      were independent prognostic factors of recurrence after MMS. LIMITATIONS: The
      limitations of our study are those of a retrospective study. CONCLUSION: Mohs
      micrographic surgery for primary high-risk BCCs has a high success rate but the
      cumulative probability of recurrence increases significantly when tumours with
      recurrences are referred for MMS.

PMID- 25383397
TI  - Penile prosthesis insertion in patients with  refractory ischaemic priapism:
      early vs  delayed implantation.
AB  - OBJECTIVE: To compare the long-term results of early and delayed insertion of a
      penile prosthesis (PP) in men with refractory ischaemic priapism (IP). PATIENTS
      AND METHODS: Early insertion of a PP was carried out in 68 men with IP within a
      median of 7 days from the onset of priapism, while 27 had delayed insertion after
      a median of 5 months. The results for sexual ability, satisfaction and subjective
      penile shortening were assessed by questioning at follow-up visits. RESULTS: In
      the early group, a malleable and an inflatable PP were implanted in 64 and four
      patients, respectively. After a median follow-up of 17 months, six patients
      needed revision surgery due to infection and curvature. Patient's satisfaction
      rate and ability to have sexual intercourse was 96%. In the delayed group, a
      malleable PP was inserted in 12 patients and an inflatable in the remaining 15.
      In all, 80% of the patients required a second corporotomy and downsized cylinders
      due to dense fibrosis. After a median follow-up of 21 months,seven patients
      required revision surgery due to infection,erosion and mechanical failure. In
      all, 25 patients were able to engage in sexual intercourse but the satisfaction
      rate was only 60% mainly due to significant penile shortening. CONCLUSIONS: Early
      PP implantation should be the preferred option inpatients with IP, as the
      procedure is technically easier, has less complication rates and allows greater
      preservation of penile length.

PMID- 25383398
TI  - Report of the 7th Meeting of  the WHO working group on  polymerase chain reaction
      protocols for detection and  subtyping of influenza viruses,  Geneva, June 2014.

PMID- 25383399
TI  - Meta-analysis of robot-assisted vs conventional  laparoscopic and open
      pyeloplasty in children.
AB  - OBJECTIVE: To critically analyse outcomes for robot-assisted pyeloplasty(RAP) vs
      conventional laparoscopic pyeloplasty (LP) or open pyeloplasty (OP) by systematic
      review and meta-analysis of published data. PATIENTS AND METHODS: Studies
      published up to December 2013 were identified from multiple literature databases.
      Only comparative studies investigating RAP vs LP or OP in children were
      included.Meta-analysis was performed using random-effects
      modelling.Heterogeneity, subgroup analysis, and quality scoring were assessed.
      Effect sizes were estimated by pooled odds ratios and weighted mean differences.
      Primary outcomes investigated were operative success, re-operation,
      conversions,postoperative complications, and urinary leakage. Secondary outcome
      measures were estimated blood loss (EBL), length of hospital stay (LOS),
      operating time (OT), analgesia requirement, and cost. RESULTS: In all, 12
      observational studies met inclusion criteria, reporting outcomes of 384 RAP, 131
      LP, and 164 OP procedures. No randomised controlled trials were identified.
      Pooled analyses determined no significant differences between RAP and LP or OP
      for all primary outcomes. Significant differences in favour of RAP were found for
      LOS (vs LP and OP). Borderline significant differences in favour of RAP were
      found for EBL(vs OP). OT was significantly longer for RAP vs OP. Limited evidence
      indicates lower opiate analgesia requirement for RAP(vs LP and OP), higher total
      costs for RAP vs OP, and comparable costs for RAP vs LP. CONCLUSIONS: Existing
      evidence shows largely comparable outcomes amongst surgical techniques available
      to treat pelvi-ureteric junction obstruction in children. RAP may offer shortened
      LOS, lower analgesia requirement (vs LP and OP), and lower EBL (vs OP); but
      compared with OP, these gains are at the expense of higher cost and longer OT.
      Higher quality evidence from prospective observational studies and clinical
      trials is required, as well as further cost-effectiveness analyses. Not all
      perceived benefits of RAP are easily amenable to quantitative assessment.

PMID- 25383400
TI  - Visceral fat accumulation is associated with  different pathological subtypes of
      renal cell  carcinoma (RCC): a multicentre study in China.
AB  - OBJECTIVE: To investigate whether visceral obesity is associated with certain
      histological subtypes of renal cell carcinoma (RCC) ina multicentre Chinese
      cohort. PATIENTS AND METHODS: A kidney tumour database was created using three
      tertiary centres in China; 487 patients were enrolled presenting with localised
      RCC and complete computer tomography(CT)/magnetic resonance imaging (MRI)
      information. A single-slice CT image was used to measure the area of visceral and
      subcutaneous adipose tissues in each patient. Statistical methods were used to
      analyse clear-cell RCC (ccRCC) and non-clear-cell RCC (non-ccRCC) as they relate
      to visceral fat area (VFA) and other risk factors, such as age, gender, tumour
      size, diabetes, hypertension, total fat area (TFA) and body mass index (BMI).
      RESULTS: In all, 418 patients had a ccRCC subtype and 69 had a non-ccRCC subtype.
      For all the patients with RCC, the mean VFA was 102 cm2, while mean BMI was 24
      kg/m2. The mean VFA was greater in ccRCC than non-ccRCC patients by 25 cm2. There
      were significant differences in the mean VFA and TFA between patients with ccRCC
      and those with non-ccRCC.Multivariate analysis showed that the presence ofVFA was
      more important than the effects of BMI and Type 2 diabetes on pathology
      prediction. In patients with a normal BMI, those with a higher quartile of VFA
      were more likely to develop ccRCC than those with a low VFA. CONCLUSIONS:
      Increased visceral fat was found to be associated with ccRCC and the significance
      of VFA outweighed the effects of BMI and Type 2 diabetes for the prediction of
      RCC pathology in multivariate analyses. As a result, VFA could constitute a
      primary explanation for the link between obesity and ccRCC.

PMID- 25383401
TI  - Improving the alkaline stability of imidazolium cations by substitution.
AB  - Imidazolium cations are promising candidates for preparing anion-exchange
      membranes because of their good alkaline stability. Substitution of imidazolium
      cations is an efficient way to improve their alkaline stability. By combining
      density functional theory calculations with experimental results, it is found
      that the LUMO energy correlates with the alkaline stability of imidazolium
      cations. The results indicate that alkyl groups are the most suitable
      substituents for the N3 position of imidazolium cations, and the LUMO energies of
      alkyl-substituted imidazolium cations depend on the electron-donating effect and
      the hyperconjugation effect. Comparing 1,2-dimethylimidazolium cations (1,2
      DMIm+) and 1,3-dimethylimidazolium cations (1,3-DMIm+) with the same substituents
      reveals that the hyperconjugation effect is more significant in influencing the
      LUMO energy of 1,3-DMIms. This investigation reveals that LUMO energy is a
      helpful aid in predicting the alkaline stability of imidazolium cations.

PMID- 25383402
TI  - On the shoulders of giants.

PMID- 25383403
TI  - Omeprazole increased small intestinal mucosal injury in two of six disease-free
      cases evaluated by capsule endoscopy.
AB  - Recently, a report showed that proton-pump inhibitors (PPI) exacerbate non
      steroidal anti-inflammatory drug-induced small intestinal injury in the rat. In
      the present report of two human cases, small intestinal injuries were probably
      induced and/or exacerbated after PPI treatment. Case 1 was a 30-year-old healthy
      man in whom no small intestinal mucosal break was detected at baseline capsule
      endoscopy. After 2 weeks of omeprazole given 20 mg once daily, he was found to
      have two small intestinal mucosal breaks. Case 2 was a 40-year-old healthy man in
      whom six small intestinal mucosal breaks were detected at baseline capsule
      endoscopy. After 2 weeks of omeprazole given 20 mg once daily, 12 small
      intestinal mucosal breaks were detected. Follow-up capsule endoscopy carried out
      3 weeks after stopping omeprazole in case 2 showed seven small intestinal mucosal
      breaks were detected, showing restitution of the small intestinalmucosal injury.
      These two cases were obtained from a pilot study evaluating the effect of single
      administration of PPI on small intestinal mucosa in humans. In the pilot study,
      six healthy male volunteers were given omeprazole 20 mg for a period of 2 weeks.
      Small intestinal injury was evaluated before and after PPI treatment using
      capsule endoscopy. In four subjects other than the two above-mentioned cases, no
      small intestinal mucosal breaks were found at both baseline and post-treatment
      capsule endoscopy. Considering the two cases with increased or newly detected
      small intestinal mucosal breaks, omeprazole may exacerbate/induce small
      intestinal injury.

PMID- 25383404
TI  - In memory of Francesco Maria Minuto.

PMID- 25383405
TI  - Preface. Rhinoviruses.

PMID- 25383406
TI  - [Nominated Renate and Wolfgang Steffen Gay and Gross honorary members of DGRh].

PMID- 25383407
TI  - [Kussmaul Medal of DGRh for Traudl Herrhausen and Emma Margarete Reil].

PMID- 25383408
TI  - [100,000 euros start-up funding for the Berlin researchers].

PMID- 25383409
TI  - [Hans Hench Prize for Rheumatology Rehabilitation and Health Services Research
      distinguishes findings for fibromyalgia syndrome].

PMID- 25383410
TI  - [Otfried-Muller-Young Investigator Award 2014 distinguished research of systemic
      sclerosis].

PMID- 25383411
TI  - Journals unite for reproducibility.

PMID- 25383412
TI  - More in New York, New Jersey infected with chikungunya: CDC.

PMID- 25383413
TI  - Fourth death caused by Mycobacterium abscessus reported at South Carolina
      hospital.

PMID- 25383414
TI  - GSK seeks approval for world's first malaria vaccine.

PMID- 25383415
TI  - Legal marijuana and pediatric exposure pot edibles implicated in spike in child
      emergency department visits.

PMID- 25383416
TI  - Obituary: Zeev Pancer  1957-2014.

PMID- 25383417
TI  - The feasibility and validity of care mapping in the clinical neurosciences.
AB  - Dementia Care Mapping (DCM) is an observational tool and process that is widely
      used in dementia care in measuring and improving person-centred care (PCC). DCM
      was previously piloted on a neurorehabilitation ward, where it was found to be
      feasible and acceptable in this setting. Following this, a new modified tool and
      accompanying manual were developed: Care Mapping - Neurorehabilitation (DCM-NR).
      The current study aimed to assess the feasibility and validity of DCM-NR by
      piloting its use in a range of clinical neuroscience settings. A mixed-methods
      design was used employing both quantitative and qualitative techniques. The new
      DCM-NR was found to be feasible for use both in terms of the suitability of its
      coding system and the implementation process. DCM-NR was shown to have a moderate
      level of concurrent validity with participants' self-report of PCC. Participants'
      subjective reports on their experiences of care provided validation for the areas
      of psychological need observed in DCM-NR. The results of this study indicate that
      DCM-NR is feasible and valid for use in a range of clinical neuroscience
      settings. Further longitudinal research is required to evaluate the impact of DCM
      NR on PCC practices over time. 

PMID- 25383418
TI  - Diagnostic value of somatosensory evoked potential changes during carotid
      endarterectomy: a systematic review and meta-analysis.
AB  - IMPORTANCE: Perioperative stroke is a persistent complication of carotid
      endarterectomy (CEA) for patients with symptomatic carotid stenosis (CS).
      OBJECTIVE: To evaluate whether changes in somatosensory evoked potential (SSEP)
      during CEA are diagnostic of perioperative stroke in patients with symptomatic
      CS. DESIGN, SETTING, AND PARTICIPANTS: We searched PubMed and the World Science
      Database for reference lists of retrieved studies and/or experiments on SSEP use
      in postoperative outcomes following CEA in patients with symptomatic CS from
      January 1, 1950, through January 1, 2013. We independently screened all titles
      and abstracts to identify studies that met the inclusion criteria and extracted
      relevant articles in a uniform manner. Inclusion criteria included randomized
      clinical trials, prospective studies, or retrospective cohort reviews; population
      of symptomatic CS; use of intraoperative SSEP monitoring during CEA; immediate
      postoperative assessment and/or as long as a 3-month follow-up; a total sample
      size of 50 or more patients; studies with adult humans 18 years or older; and
      studies published in English. MAIN OUTCOME AND MEASURE: Whether intraoperative
      SSEP changes were diagnostic of perioperative stroke indicated by postoperative
      neurological examination. RESULTS: Four-hundred sixty-four articles were
      retrieved, and 15 prospective and retrospective cohort studies were included in
      the data analysis. A 4557-patient cohort composed the total sample population for
      all the studies, 3899 of whom had symptomatic CS. A change in SSEP exhibited a
      strong pooled mean specificity of 91% (95% CI, 86-94) but a weaker pooled mean
      sensitivity of 58% (95% CI, 49-68). A pooled diagnostic odds ratio for individual
      studies of patients with neurological deficit with changes in SSEPs was 14.39
      (95% CI, 8.34-24.82), indicating that the odds of observing an SSEP change among
      those with neurologic deficits were 14 times higher than in individuals without
      neurologic deficit. CONCLUSIONS AND RELEVANCE: Intraoperative SSEP is a highly
      specific test in predicting neurological outcome following CEA. Patients with
      perioperative neurological deficits are 14 times more likely to have had changes
      in SSEPs during the procedure. The use of SSEPs to design prevention strategies
      is valuable in reducing perioperative cerebral infarctions during CEA.

PMID- 25383419
TI  - Mycobacterium tuberculosis enoyl-acyl carrier protein reductase inhibitors as
      potential antituberculotics: development in the past decade.
AB  - Mycobacterial enoyl-ACP-reductase, an enzyme contributing in mycolic acids
      biosynthesis, has been established as promising target of novel antimycobacterial
      drugs. The development of inhibitors active without previous activation by
      catalase/peroxidase system (e.g. isoniazid), seems to be rational approach.
      Catalase/peroxidase system is frequently responsible for resistance. We hereby
      present a review of direct mycobacterial enoyl-acyl carrier protein reductase
      inhibitors development in past decade. A special attention was paid to mechanism
      of inhibition, which shows relatively conserved interactions of inhibitors with
      Tyr 158 and cofactor. Hence, future developments of more effective antitubercular
      drugs should consider structural demands for potent direct mycobacterial enoyl
      reductase inhibitors. 

PMID- 25383420
TI  - The withdrawal of drugs for commercial reasons: the incomplete story of
      tositumomab.

PMID- 25383421
TI  - Regioselective Asao-Yamamoto benzannulations of diaryl acetylenes.
AB  - Asao-Yamamoto benzannulations transform diarylalkynes into 2,3
      diarylnaphthalenes, and regioselective variants of this reaction are of interest
      for synthesizing substituted polycyclic aromatic systems. It is shown that
      regioselective cycloadditions occur when one alkyne carbon preferentially
      stabilizes developing positive charge. Simple calculations of the relative
      energies of carbocations localized at each alkyne carbon of a substrate predict
      the regioselectivity, which is not eroded by bulky substituents, including 2,6
      disubstituted aryl groups. 

PMID- 25383422
TI  - Discovery of 2-(cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as
      a new series of potent phosphodiesterase 7 inhibitors.
AB  - The discovery of a new series of potent phosphodiesterase 7 (PDE7) inhibitors is
      described. Novel thieno[3,2-d]pyrimidin-4(3H)-one hit compounds were identified
      from our chemical library. Preliminary modifications of the hit compounds were
      performed, resulting in the discovery of a fragment-sized compound (10) with
      highly improved ligand efficiency. Compound design was guided by structure
      activity relationships and computational modeling. The 6-substituted derivatives
      of the thienopyrimidinone showed diminished activity and enzyme selectivity.
      However, synthesis of the 7-substituted derivatives resulted in the discovery of
      28e, a desirable lead compound that selectively inhibits PDE7 with single-digit
      nanomolar potency while displaying potent cellular efficacy. 

PMID- 25383423
TI  - Thiazolidine derivatives from fluorescent dithienyl-BODIPY-carboxaldehydes and
      cysteine.
AB  - Fluorescent dithienyl-borondipyrromethene (BODIPY) dyes formylated in the beta'
      position (2b, 2c) have been treated with L-cysteine to provide thiazolidine
      derivatives. N-Protection of the thiazolidine unit by ethoxycarbonylation
      facilitated isolation of the two major diasteroisomers 6 and 7. These
      stereoisomers have been fully characterized by (1)H NMR spectroscopy, allowing
      assignment of their stereochemistry as 2R,4R,aS and 2S,4R,aR, respectively. The
      optical properties of the thiazolidine dyes differ markedly in both absorption
      (lambda(abs) = 612 nm for 6 and 615 nm for 7) and emission (lambda(em) = 669 nm,
      Phi(F) = 62% for 6 and lambda(em) = 672 nm, Phi(F) = 19% for 7) from those of the
      BODIPY-carboxaldehydes 2b (lambda(abs) = 643 nm and lambda(em) = 719 nm, Phi(F) =
      26%) and 2c (lambda(abs) = 636 nm and lambda(em) = 710 nm, Phi(F) = 36%). In a
      mixed solvent [phosphate buffer saline (PBS), pH = 7.4/ethanol 1:9], the
      fluorescence response of the dyes in the presence of L-cysteine is slow, but a
      ratiometric detection process in the therapeutic window (650 to 800 nm) is
      evident.

PMID- 25383424
TI  - The future of emergency medicine.

PMID- 25383425
TI  - NHS: a brave new world? Reflections on the Five Year Forward View.

PMID- 25383428
TI  - A clinical analysis of the emergency medicine workforce crisis.
AB  - Workforce crises in medicine can be devastating for a specialty, patients and
      professionals. Emergency medicine and general practice are currently affected but
      other acute specialties are showing early signs and symptoms of the condition.
      While symptomatic treatments are helpful, recognition and treatment of the causes
      is critical. 

PMID- 25383429
TI  - Sustainable working practices and minimizing burnout in emergency medicine.
AB  - Sustainable and satisfying working practices in emergency medicine are vital to
      produce career longevity and prevent premature 'burnout'. A range of strategies
      is required to ensure success for the individual and the system in which he/she
      works. 

PMID- 25383430
TI  - What has the 4-hour access standard achieved?
AB  - Few performance management measures create as much heat and debate as the 4-hour
      target for emergency departments. This article critically reviews the history,
      evidence and effectiveness of the 4-hour standard for patients attending
      emergency departments. 

PMID- 25383431
TI  - Exit block in the emergency department: recognition and consequences.
AB  - Exit block and crowding create conditions in emergency departments that can harm
      patients and the staff who look after them. Key to solving exit block is
      recognizing that it exists and that the whole hospital is involved in preventing
      harmful consequences. 

PMID- 25383432
TI  - Better data, better planning: the College of Emergency Medicine sentinel sites
      project.
AB  - This article describes the College of Emergency Medicine's initial attempt to
      gather high quality data from its own 'sentinel sites' rather than relying on
      more comprehensive national data of dubious quality. Such information is
      essential to inform and guide the planning of urgent and emergency care services
      in the future. 

PMID- 25383433
TI  - Tariffs in emergency care.
AB  - The crisis in emergency medicine in the UK was no surprise to staff in the
      specialty, but was not expected by the Department of Health. This article
      explains how chronic, systematic under-resourcing of emergency care has caused
      emergency departments to decompensate, and discusses actions that are necessary
      to prevent recurrence. 

PMID- 25383434
TI  - 'Big data' approaches to trauma outcome prediction and autonomous resuscitation.
AB  - Massive clinical digital data routinely collected by high throughput biomedical
      devices provide opportunities and challenges for optimal use. This article
      discusses how such data are used in learning prediction models at level 1 trauma
      centres to support decision making in trauma patients. 

PMID- 25383435
TI  - Do we need 'routine' blood counts?
AB  - Performing daily blood counts has become a routine part of hospital practice but
      with limited thought given to the need for them. In addition, the occasional
      abnormalities in these tests trigger further investigations which may have not
      been necessary if clinical examination was given adequate importance. 

PMID- 25383436
TI  - Charles Barrett Lockwood: victim of an occupational hazard of surgeons.

PMID- 25383437
TI  - Does rapid assessment shorten the amount of time patients spend in the emergency
      department?
AB  - BACKGROUND: Overcrowding in the emergency department is a common phenomenon. This
      study assessed the impact of introducing a consultant-supported rapid assessment
      model, known as EDIT, and point of care testing upon the length of time patients
      spend in the emergency department. METHODS: A prospective, observational cohort
      study was conducted in an emergency department in a district general hospital in
      the UK. The study consisted of two phases. Patients who attended the emergency
      department during phase 1 were assessed using a nurse-led triage model with blood
      samples being analysed in a centralized hospital laboratory. Phase 2 patients
      were assessed by a consultant-supported rapid assessment model with blood tests
      being analysed using point of care testing. The time from patient arrival in the
      emergency department to the time that care was complete and the patient was ready
      to move on to the next destination of care was recorded. These times from the two
      phases were compared using the Wilcoxon rank sum test. RESULTS: A total of 11 213
      patients attended the emergency department during the whole study period, of whom
      4622 patients were eligible for the study. Phase 1 contained 3835 patients and
      phase 2 had 787 patients. The median time for patients to be declared ready to
      leave the emergency department in phase 1 was 129 minutes compared to 76 minutes
      for phase 2 (P=0.0025). This was a reduction in the median of 53 minutes or 41.1%
      (95% confidence interval 39.7-42.3%). CONCLUSIONS: This study demonstrates that a
      consultant-supported rapid assessment model using point of care testing
      significantly shortens the time patients spend in the emergency department.

PMID- 25383438
TI  - A 72-year-old woman with a persistent cough and abnormal chest X-ray.

PMID- 25383439
TI  - Kounis syndrome secondary to food allergy.

PMID- 25383440
TI  - A man with facial changes.

PMID- 25383441
TI  - Pulmonary mycetoma.

PMID- 25383443
TI  - Using ultrasound for percutaneous tracheostomy: is it time to change practice?

PMID- 25383444
TI  - Self-assembled levan nanoparticles for targeted breast cancer imaging.
AB  - We report on the targeted imaging of breast cancer using self-assembled levan
      nanoparticles. Indocyanine green (ICG) was encapsulated in levan nanoparticles
      via self-assembly. Levan-ICG nanoparticles were found to be successfully
      accumulated in breast cancer via specific interaction between fructose moieties
      in levan and overexpressed glucose transporter 5 in breast cancer cells. 

PMID- 25383446
TI  - Brain tumors in Sweden: data from a population-based registry 1999-2012.
AB  - BACKGROUND: The Swedish brain tumor registry has, since it was launched in 1999,
      provided significant amounts of data on histopathological diagnoses and on
      important aspects of surgical and medical management of these patients. The
      purpose is mainly quality control, but also as a resource for research. METHODS:
      Three Swedish healthcare regions, constituting 40% of the Swedish population,
      have had an almost complete registration. The following parameters are
      registered: diagnosis according to SNOMED/WHO classification, symptoms,
      performance status, pre- and postoperative radiology, tumor size and
      localization, extent of surgery and occurrence of postoperative complications,
      postoperative treatment, such as radiotherapy and/or chemotherapy, other
      treatments, complications and toxicity, occurrence of reoperation/s,
      participation in clinical trials, multidisciplinary conferences and availability
      of a contact nurse. RESULTS: Surgical radicality has been essentially constant,
      whereas the use of early (within 72 hours) postoperative CT and MRI has
      increased, especially for high-grade glioma, which is a reflection of quality of
      surgery. Survival of patients with high-grade glioma has increased, especially in
      the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%.
      Waiting times for the pathological report has been slightly prolonged.
      Geographical differences do exist for some of the variables. CONCLUSION:
      Population-based registration is valuable for assessment of clinical management,
      which could have impact on patient care. As a result of short survival and/or the
      propensity to affect cognitive functions this patient group has considerable
      difficulties to make their voices heard in society. We therefore believe that a
      report like the present one can contribute to the spread of knowledge and
      increase the awareness for this patient group among caregivers and policy makers.

PMID- 25383448
TI  - A retrospective safety and efficacy analysis of the first patients treated with
      eribulin for metastatic breast cancer in Stockholm, Sweden.
AB  - BACKGROUNDS: Eribulin is a non-taxane, microtubule dynamics inhibitor approved
      for the treatment of patients with metastatic breast cancer (MBC) in Europe in
      March 2011. MATERIAL AND METHODS: For the purpose of an internal quality control,
      all patients with MBC treated with eribulin at Karolinska University Hospital
      were registered in a database. Clinical data were collected retrospectively for
      patients that were registered by August 2012 and safety and efficacy of eribulin
      were evaluated. Treatment toxicity including fatigue, neurotoxicity and infection
      was graded according to CTCAE v4.0. Objective response to treatment was
      investigated using routinely performed radiological assessments. When only
      clinical assessments were made, the evaluation of the treating physician was
      used. Furthermore, the efficacy of eribulin was investigated in different tumor
      subtypes. RESULTS: Forty-eight patients who received at least one cycle of
      eribulin were identified. Most patients were heavily pretreated with a median of
      3 (range 1-7) previous chemotherapy lines prior to eribulin. Median patient age
      was 56 years (range 35-74). At the end of the analysis, 23 patients were alive
      and two were still treated with eribulin. No hypersensitivity reactions and no
      toxic deaths were seen. Fatigue grade 3-4 was observed in three patients (6.3%).
      One patient experienced grade 4 neurotoxicity. Grade 3-4 neutropenia was
      documented in 18.8%, and three patients were treated for a grade 3 infection.
      Interestingly, three individuals developed Herpes zoster reactivation. One
      patient responded to treatment with complete remission, while 33.3% had a partial
      response. 48% of all patients had a clinical benefit (objective response or
      stable disease for more than six months). CONCLUSIONS: Eribulin administered
      outside of a clinical trial in patients with advanced breast cancer was safe and
      well tolerated. A clinical benefit was seen in half of the cases. No
      statistically significant differences in objective response or survival were
      observed between histopathological subgroups.

PMID- 25383447
TI  - Common filaggrin gene mutations and risk of cervical cancer.
AB  - BACKGROUND: As carriers of filaggrin gene (FLG) mutations may have a compromised
      cervical mucosal barrier against human papillomavirus infection, our primary
      objective was to study their risk of cervical cancer. METHODS: We genotyped 586
      cervical cancer patients for the two most common FLG mutations, R501X and
      2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n
      = 8050) were genotyped in previous population-based studies. Information on
      cervical cancer, mortality and emigration were obtained from national registers.
      Odds ratios (OR) were estimated by logistic regression with adjustment for age at
      blood sampling, and weighted by the genotype-specific inverse probability of
      death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox
      regression with time since diagnosis as underlying time, and with adjustment for
      age at diagnosis and stratification by cancer stage. RESULTS: The primary results
      showed that FLG mutations were not associated with the risk of cervical cancer
      (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57
      1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations
      increased mortality due to cervical cancer (HR 4.55, 95% CI 1.70-12.2), however,
      the association was reduced after stratification by cancer stage (HR 2.53, 95% CI
      0.84-7.59). CONCLUSION: Carriage of FLG mutations was not associated with the
      risk of cervical cancer.

PMID- 25383445
TI  - Particle therapy for clinically diagnosed stage I lung cancer: comparison with
      pathologically proven non-small cell lung cancer.
AB  - BACKGROUND: The purpose of the present study was to present the treatment
      outcomes of particle therapy for indeterminate pulmonary nodules (IPNs) diagnosed
      as stage I non-small cell lung cancer, including a comparative analysis involving
      pathologically proven lung cancer (PPLC). MATERIAL AND METHODS: A total of 54
      patients (57 lesions) who underwent particle therapy for IPNs were enrolled in
      this study. Median patient age was 76 (range 52-87) years. T-classification was:
      T1a, 30; T1b, 16; and T2a, 11. Particle therapy using protons or carbon ions was
      delivered at total doses of 52.8-80 Gy equivalent in 4-26 fractions. The PPLC
      cohort included 111 patients. RESULTS: The median follow-up time was 41 (range 7
      90) months. For all IPN patients, the three-year overall survival, progression
      free survival, local control and distant progression-free survival rates were
      90%, 72%, 94% and 79%, respectively. Grade 2 toxicities were radiation
      pneumonitis (19%), dermatitis (9%), rib fracture (2%), chest wall pain (2%) and
      neuropathy (2%). No >=grade 3 toxicities were observed. In univariate analysis,
      the IPN group showed significantly better survival relative to the PPLC group.
      However, after adjustment for baseline imbalances between these two groups in
      multivariate analysis, pathological confirmation did not correlate with survival.
      CONCLUSIONS: Particle therapy for IPNs provided favorable outcomes with minimal
      toxicities, which may be comparable to those for PPLC patients. Further studies
      are needed to clarify the optimal management of IPN patients.

PMID- 25383449
TI  - Docetaxel-induced neuropathy: a pharmacogenetic case-control study of 150 women
      with early-stage breast cancer.
AB  - BACKGROUND: Docetaxel is a highly effective treatment of a wide range of
      malignancies but is often associated with peripheral neuropathy. The genetic
      variability of genes involved in the transportation or metabolism of docetaxel
      may be responsible for the variation in docetaxel-induced peripheral neuropathy
      (DIPN). The main purpose of this study was to investigate the impact of genetic
      variants in GSTP1 and ABCB1 on DIPN. MATERIAL AND METHODS: DNA was extracted from
      whole blood from 150 patients with early-stage breast cancer who had received
      adjuvant docetaxel from February 2011 to May 2012. Two polymorphisms in GSTP1 and
      three in ABCB1 were selected for the primary analysis, and a host of other
      candidate genes was explored and compared between 75 patients with clinician
      reported DIPN grade >= 2 and 75 patients without DIPN. RESULTS: Patients with the
      genetic variants GSTP1 rs1138272 C/T or T/T (114Ala/114Val or 114Val/114Val)
      genotype had an adjusted odds ratio of 3.82; 95% confidence interval 1.34-11.09
      of developing DIPN. This result was confirmed in both analysis of cumulated
      docetaxel dose and haplotype analysis. None of the explorative genes investigated
      were significantly correlated with DIPN. Patients with a BMI >= 30 were five-fold
      more likely to have DIPN than patients with BMI < 25. CONCLUSION: We found that
      GSTP1 Ala114Val polymorphism is associated with occurrence of DIPN. This supports
      the theory that oxidative stress is involved in DIPN pathophysiology. If
      confirmed, this may be helpful in the risk assessment of DIPN and perhaps help to
      achieve better management of neurotoxicity.

PMID- 25383450
TI  - Improving radiotherapy planning for large volume lung cancer: a dosimetric
      comparison between hybrid-IMRT and RapidArc.

PMID- 25383451
TI  - Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic
      breast density in postmenopausal breast cancer patients: a Dutch TEAM trial
      analysis.
AB  - BACKGROUND: Mammographic breast density is one of the strongest independent risk
      factors for developing breast cancer. We examined the effect of exemestane and
      tamoxifen on breast density in Dutch postmenopausal early breast cancer patients
      participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.
      MATERIAL AND METHODS: Analogue mammograms of selected TEAM participants before
      start, and after one and two (and if available after three) years of adjuvant
      endocrine therapy were collected centrally and reviewed. Study endpoints were
      change in breast density over time, and correlations between breast density and
      locoregional recurrence (LRR), distance recurrence (DR), and contralateral breast
      cancer (CBC). RESULTS: Mammograms of 378 patients (181 tamoxifen, 197 exemestane)
      were included in the current per protocol analyses. Baseline breast density was
      low (breast density score<50% in 75% of patients) and not different between
      patients randomised to exemestane or tamoxifen (coefficient 0.16, standard error
      0.17). Breast density did not change during treatment in exemestane (p=0.25) or
      tamoxifen users (p=0.59). No relation was observed between breast density and the
      occurrence of a LRR [hazards ratio (HR) 0.87, 95% CI 0.45-1.68, p=0.67], a DR (HR
      1.02, 95% CI 0.77-1.35, p=0.90), or CBC (HR 1.31, 95% CI 0.63-2.72, p=0.48).
      CONCLUSION: The in general low breast density score in early postmenopausal
      breast cancer patients did not substantially change over time, and this pattern
      was not different between tamoxifen and exemestane users. Breast density was not
      a predictive marker for efficacy of adjuvant endocrine therapy.

PMID- 25383452
TI  - Technical evaluation of a laser-based optical surface scanning system for
      prospective and retrospective breathing adapted computed tomography.
AB  - BACKGROUND: For breathing adapted radiotherapy, the same motion monitoring system
      can be used for imaging and triggering of the accelerator. PURPOSE: To evaluate a
      new technique for prospective gated computed tomography (CT) and four-dimensional
      CT (4DCT) using a laser based surface scanning system (Sentinel(TM), C-RAD,
      Uppsala, Sweden). The system was compared to the AZ-733V respiratory gating
      system (Anzai Medical, Tokyo, Japan) and the Real-Time Position Management System
      (RPM(TM)) (Varian Medical Systems, Palo Alto, CA, USA). MATERIAL AND METHODS:
      Temporal accuracy was evaluated using a moving phantom programmed to move a
      platform along trajectories following a sin(6)(omegat) function with amplitudes
      from 6 to 20 mm and periods from 2 to 5 s during 120 s while the motion was
      recorded. The recorded data was Fourier transformed and the peak area at the
      fundamental and harmonic frequencies compared to data generated using the same
      sinusoidal function. For verification of the 4DCT reconstruction process, the
      phantom was programmed to move along a sinusoidal trajectory. Ten phase series
      were reconstructed. The distance from the couch to the platform was measured in
      each image. By fitting the function sin(omegat-phi) to the values measured in the
      images corresponding to each slice, the phase of each image was verified. RESULTS
      AND CONCLUSION: In the recorded data, the peak area at the fundamental frequency
      covered on average 104 +/- 4%, 102 +/- 4% and 91 +/- 27% of the peak area in the
      generated data for the Sentinel(TM), RPM(TM) and AZ-733V systems, respectively.
      All systems managed to resolve both harmonic frequencies. The second experiment
      showed that all images were sorted into the correct series using breathing data
      recorded by each system. The systems generated very similar results, however, it
      is preferable to use the same system both for imaging and treatment.

PMID- 25383453
TI  - Viscothionin isolated from Korean mistletoe improves nonalcoholic fatty liver
      disease via the activation of adenosine monophosphate-activated protein kinase.
AB  - The present study investigated the effects of viscothionin, a compound isolated
      from Korean mistletoe (Viscum album coloratum), on nonalcoholic fatty liver
      disease (NAFLD) in both in vitro and in vivo models. A connection was discovered
      between viscothionin and the adenosine monophosphate-activated protein kinase
      (AMPK) signaling pathway, which is involved in lipid metabolism. Viscothionin was
      shown to significantly attenuate lipid accumulation in HepG2 cells treated with
      oleic acid, which induces lipid accumulation. Moreover, the phosphorylation of
      AMPK and acetyl-coenzyme A carboxylase in HepG2 cells was increased by
      viscothionin treatment. Viscothionin was orally administered to high fat diet
      induced obese mice and subsequently histopathological analysis associated with
      AMPK signaling pathways was evaluated. A significant reduction in the extent of
      hepatic steatosis was revealed in viscothionin-treated obese mice. Thus,
      viscothionin mediates its beneficial effects on NAFLD via AMPK signaling
      pathways, suggesting that it may be a potential target for novel NAFLD
      treatments. 

PMID- 25383460
TI  - Beta-frequency EEG activity increased during transcranial direct current
      stimulation.
AB  - Transcranial direct current stimulation (tDCS) is a technique for noninvasively
      stimulating specific cortical regions of the brain with small (<2 mA) and
      constant direct current on the scalp. tDCS has been widely applied, not only for
      medical treatment, but also for cognitive and somatosensory function enhancement,
      motor learning improvement, and social behavioral change. However, the mechanism
      that underlies the effect of tDCS is unclear. In this study, we performed
      simultaneous electroencephalogram (EEG) monitoring during tDCS to understand the
      dynamic electrophysiological changes throughout the stimulation. A total of 10
      healthy individuals participated in this experiment. We recorded EEGs with direct
      current stimulation, as well as during a 5-min resting state before and after the
      stimulation. All participants kept their eyes closed during the experiment. Anode
      and cathode patches of tDCS were placed on the left and the right dorsolateral
      prefrontal cortex, respectively. In addition, an EEG electrode was placed on the
      medial prefrontal cortex. The beta-frequency power increased promptly after
      starting the stimulation. The significant beta-power increase was maintained
      during the stimulation. Other frequency bands did not show any significant
      changes. The results indicate that tDCS of the left dorsolateral prefrontal
      cortex changed the brain to a ready state for efficient cognitive functioning by
      increasing the beta-frequency power. This is the first attempt to simultaneously
      stimulate the cortex and record the EEG and then systematically analyze the
      prestimulation, during-stimulation, and poststimulation EEG data.

PMID- 25383459
TI  - Association between morphologic CT imaging traits and prognostically relevant
      gene signatures in women with high-grade serous ovarian cancer: a hypothesis
      generating study.
AB  - PURPOSE: To investigate associations among imaging traits observed on computed
      tomographic (CT) images, Classification of Ovarian Cancer (CLOVAR) gene
      signatures, and survival in women with high-grade serous ovarian cancer (HGSOC).
      MATERIALS AND METHODS: The institutional review board approved this HIPAA
      compliant retrospective study of CT images obtained before cytoreductive surgery
      in 46 women with HGSOC, whose tumors were subjected to molecular analysis
      performed by the Cancer Genome Atlas Research Network. Two readers independently
      evaluated the CT features of the primary ovarian mass and sites of metastatic
      spread if present, including size, outline, and texture. Fisher exact test was
      used to examine the relationship between imaging traits and CLOVAR subtypes
      (CLOVAR differentiated, immunoreactive, mesenchymal, and proliferative). Kaplan
      Meier and Cox proportional hazards regression survival analyses were performed.
      RESULTS: The presence of mesenteric infiltration and diffuse peritoneal
      involvement by tumor at CT were significantly associated with CLOVAR subtype (P =
      .002-.004 for reader 1 and P = .005-.012 for reader 2). Mesenteric infiltration
      at CT was associated with CLOVAR mesenchymal subtype. Patients with mesenteric
      infiltration had shorter median progression-free survival than patients without
      mesenteric involvement (14.7 months vs 25.6 months according to both readers; P =
      .019 for reader 1 and .015 for reader 2) and overall survival (49.0 vs 58.2
      months; P = .014 [reader 1] and 50.0 vs 59.1 months; P = .015 [reader 2]). No
      other imaging features were significantly associated with CLOVAR subtype or
      survival. CONCLUSION: Specific CT imaging traits were associated with the CLOVAR
      subtypes and survival in patients with HGSOC.

PMID- 25383461
TI  - Increased vascular MMP-9 in mice lacking RNF213: moyamoya disease susceptibility
      gene.
AB  - Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with
      unknown etiology. Recent genetic studies have identified RNF213 as an important
      susceptibility gene for MMD. To evaluate the role of RNF213 in vascular
      remodeling, RNF213 knockout mice (RNF213-/-) and their wild-type littermates (WT)
      were subjected to common carotid artery ligation to induce vascular hyperplasia.
      We examined the vascular expression of matrix metalloproteinase (MMP)-9, known to
      be increased in MMD. MMP-9 expression was significantly higher in RNF213-/- mice
      than in wild-type mice 1 and 7 days after common carotid artery ligation. The
      vascular wall was significantly thinner in RNF213-/- mice at 14 days. The
      increased vascular expression of MMP-9 and subsequent vascular wall thinning in
      RNF213-/- mice could reflect the early characteristic of MMD, consistent with the
      recently proposed constrictive remodeling theory. 

PMID- 25383462
TI  - Plasma levels of copeptin predict 1-year mortality in patients with acute
      ischemic stroke.
AB  - To evaluate the association between plasma levels of copeptin and 1-year
      mortality in a cohort of Chinese patients with acute ischemic stroke. We
      prospectively studied 275 patients with ischemic stroke who were admitted within
      24 h after the onset of symptoms. Copeptin and NIH stroke scale (NIHSS) score
      were measured at the time of admission. The prognostic value of copeptin to
      predict mortality within 1 year was compared with the NIHSS score and other known
      outcome predictors. Nonsurvivors had significantly higher copeptin levels on
      admission compared with survivors (P<0.0001). Multivariate logistic regression
      analysis showed that elevated plasma levels of copeptin were an independent
      stroke mortality predictor, with an adjusted odds ratio of 4.48 [95% confidence
      interval (CI), 2.18-9.06]. The area under the receiver operating characteristic
      curve of copeptin was 0.882 (95% CI, 0.847-0.921) for stroke mortality, which
      yielded a sensitivity of 90.7% and a specificity of 84.5%. Copeptin improved the
      NIHSS score (area under the curve of the combined model, 0.94; 95% CI, 0.91-0.97;
      P=0.011). Elevated plasma copeptin levels at admission were an independent
      predictor of long-term mortality after ischemic stroke in a Chinese sample,
      suggesting that these alterations might play a role in the pathophysiology of
      stroke.

PMID- 25383463
TI  - Neuropeptide Y and alpha-melanocyte-stimulating hormone reciprocally regulate
      nesfatin-1 neurons in the paraventricular nucleus of the hypothalamus.
AB  - Nesfatin-1 is an 82 amino acids peptide processed from its precursor nucleobindin
      2 (NUCB2). Accumulating evidences have shown that the nesfatin-1/NUCB2 localized
      in the paraventricular nucleus (PVN) of the hypothalamus regulates food intake
      and energy metabolism. However, the factors that regulate nesfatin-1/NUCB2
      neurons in PVN are less defined. In the hypothalamic feeding center, the second
      order neurons in PVN are extensively projected by the first-order neurons in the
      arcuate nucleus (ARC), the representatives of which are orexigenic neuropeptide Y
      (NPY) and anorexigenic alpha-melanocyte-stimulating hormone (alpha-MSH) neurons.
      The present study explored whether NPY and alpha-MSH regulate the PVN nesfatin
      1/NUCB2 neurons. This was achieved by cytosolic Ca ([Ca]i) imaging, followed by
      nesfatin-1/NUCB2 immunostaining in single neurons isolated from PVN. The moderate
      increase in [Ca]i with 5 mM glucose was suppressed by NPY, but further increased
      by alpha-MSH in the PVN neurons that were shown to be immunoreactive to nesfatin
      1/NUCB2. The majority (60%) of nesfatin-1/NUCB2 neurons in PVN responded to NPY
      and/or alpha-MSH. Confocal immunohistochemical images showed that both NPY and
      alpha-MSH neuronal terminals contacted nesfatin-1/NUCB2 neurons in PVN. These
      data show that NPY inhibits and alpha-MSH activates PVN nesfatin-1/NUCB2 neurons,
      presenting dual and reciprocal neuro-circuits from ARC to PVN, possibly
      contributing toward the balanced regulation of feeding.

PMID- 25383464
TI  - Systematic Occlusion of Shunts: Control of Early Postoperative IOP and Hypotony
      related Complications Following Glaucoma Shunt Surgery.
AB  - OBJECTIVE: Evaluation of a protocol of total intraluminal occlusion of Baerveldt
      shunts and its effects on early postoperative intraocular pressure (IOP) control
      and hypotony-related complications. DESIGN: This was a noncomparative,
      prospective, and interventional study. PARTICIPANTS: Glaucoma patients were
      recruited to undergo Baerveldt shunt surgery. A total of 116 eyes of 112 patients
      were enrolled. INTERVENTION: During shunt implantation, aqueous outflow was
      restricted using an intraluminal occluding stent inserted through the entire tube
      length, with and without external ligation, to halt aqueous flow.
      Postoperatively, eyes underwent ligature laser suture lysis and partial or
      complete stent removals, at predetermined time intervals. MAIN OUTCOME MEASURE:
      Loss of postoperative IOP control was categorized as transient or persistent
      hypotony (IOP<=5 mm Hg) or hypertony (IOP>21 mm Hg). Patients were followed up
      for 1 year. RESULTS: Preoperatively median IOP was 23 mm Hg (mean 26 mm Hg, SD 12
      mm Hg), median number of glaucoma medications was 3.0 (mean 3.0, SD 1.2). During
      year 1, laser suture lysis was performed in 30 eyes (26%) and stent removal in 93
      eyes (80%) (23 partial; 70 complete). There was 1 case of transient hypotony, no
      cases of persistent hypotony, 10 of transient hypertony, and 3 of persistent
      hypertony. Nine eyes had IOP<=5 mm Hg at >=1 time points and hypotony-related
      complications occurred in 8 eyes (7%). At 1 year, median IOP was 12 mm Hg (mean
      13 mm Hg, SD 4 mm Hg) with a median of 1.0 glaucoma medications (mean 1.1, SD
      1.3). The cumulative probability of failure during the first 12 months follow-up
      was 6% (n=7). Overall postoperative complications occurred in 11 eyes (9%).
      CONCLUSIONS: The surgical and postoperative protocol resulted in controlled, step
      wise reductions of IOP with low rates of hypotony and related complications.

PMID- 25383465
TI  - Risk Factors for a Severe Bleb Leak Following Trabeculectomy: A Retrospective
      Case-Control Study.
AB  - PURPOSE: To describe the population at risk of having a severe bleb leak needing
      a surgical repair in the operating room and to study risk factors associated with
      severe bleb leak. PATIENTS AND METHODS: In this case-control study, 17 cases were
      enrolled and paired with 51 controls. We studied all patients having a surgical
      revision in our center for a severe bleb leak between January 1 and December 31,
      2008. Three controls were paired to each case based on their surgery date. We
      then analyzed risk factors related to the patient, the intervention, and the
      postoperative follow-up. RESULTS: Younger age was the only statistically
      significant risk factor for a severe bleb leak in our study. The odds of a severe
      bleb leak decreased as the age increased (P=0.0029). In comparing the risk for a
      severe bleb leak in younger (below 55 y) versus patients aged 75 years or older,
      the odds ratio was 21.0. There were no statistically significant differences
      between cases and controls with respect to: type of glaucoma, number or types of
      previous ocular surgeries, number of preoperative topical medications,
      localization of the leak, localization of the wound (fornix or limbus-based), or
      the intraocular pressure on day 1 postoperative. CONCLUSIONS: Younger age at the
      time of trabeculectomy may be a risk factor for severe bleb leak. A trend was
      observed in which the patients under the age of 55 years were at greater risk for
      a severe bleb leak.

PMID- 25383466
TI  - Meta-analysis of the Efficacy and Safety of Latanoprost Monotherapy in Patients
      With Angle-closure Glaucoma.
AB  - PURPOSE: To systematically evaluate the safety and efficacy of latanoprost
      monotherapy for the treatment of patients with angle-closure glaucoma. METHODS:
      We searched EMBASE, Medline, Cochrane Library, Chinese Journal Full-text Database
      (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wang Fang
      using the search terms "latanoprost" (or its commercial name, Xalatan) and "angle
      closure glaucoma." Resulting articles were then screened using preset inclusion
      criteria. Subgroup and sensitivity analyses were performed to evaluate the impact
      of research population, research type (blinded or controlled), and
      withdrawal/loss to follow-up. RESULTS: A total of 17 studies (n=807) were
      included in this meta-analysis. The primary outcome measure was intraocular
      pressure (IOP). Changes in the mean, peak, and trough IOP from baseline were used
      as effect measures. As I statistic revealed statistical heterogeneity, the random
      effects model was applied. With the exception of 2 non-Asian populations from
      Australia and Peru, all 13 countries included in this study were from Asia.
      Latanoprost reduced mean IOP by 7.9 mm Hg (32.4%), peak IOP by 7.4 mm Hg (29.8%),
      and trough IOP by 7.9 mm Hg (32.5%). The most frequent ocular adverse effects
      were ocular hyperemia, discomfort (including eye irritation, ocular discomfort,
      foreign body sensation, and itching), and blurred vision with a total incidence
      rate of 9.4%, 8.7%, and 5.2%, respectively. Systemic adverse effects encompass
      rhinitis, dizziness, headache, and nonspecific skin pigmentation. CONCLUSIONS:
      Latanoprost is effective at reducing the IOP of patients with angle-closure
      glaucoma. Adverse reactions associated with latanoprost were mainly ocular in
      nature.

PMID- 25383467
TI  - The Effect of Long-term Antiglaucomatous Drug Administration on Central Corneal
      Thickness.
AB  - PURPOSE: To evaluate rates of changes per year of central corneal thickness after
      antiglaucomatous drug administration with beta-blockers, prostaglandin analogs,
      and carbonic anhydrase inhibitors monotherapy and combined topical
      antiglaucomatous therapy, in a cohort of patients with ocular hypertension,
      glaucoma suspects, and patients with perimetric glaucoma as compared with normal
      controls. PATIENTS AND METHODS: This retrospective single-center study included
      130 eyes as healthy controls, 121 eyes of ocular hypertensive patients, 105 eyes
      of glaucoma suspects, and 49 eyes of perimetric glaucoma patients. All patients
      underwent standard automated perimetry, 24-hour intraocular pressure profile,
      optic disc photography, and optical coherence pachymetry (OCP; Heidelberg
      Engineering). The cohort was divided into 8 groups on the basis of topical
      antiglaucomatous medication. Linear regression analysis was conducted to analyze
      the relationship between central corneal thickness and exposure to
      antiglaucomatous medication during the follow-up. RESULTS: Central corneal
      thickness did not change during the follow-up for investigated diagnostic
      subgroups. There was a statistically significant decrease in central corneal
      thickness for eyes treated with prostaglandin monotherapy (-3.1 MUm/y for left
      eye), and a combined therapy with prostaglandins, carbonic anhydrase inhibitors,
      and beta-blockers (-5.8 and -3.8 MUm/y for right and left eye, respectively).
      CONCLUSIONS: We recommend regular measurements before and during therapy with
      prostaglandin monotherapy and a combined therapy with prostaglandins, carbonic
      anhydrase inhibitors, and beta-blockers. Follow-up intraocular pressure
      measurements may be underestimated for eyes treated with the aforementioned
      treatment regimens if central corneal thickness is not measured on a regular
      basis.

PMID- 25383468
TI  - Rebuttal canaloplasty after failed trabeculectomy: a possible option.

PMID- 25383469
TI  - Change in retinal nerve fiber layer thickness after trabeculectomy.

PMID- 25383470
TI  - Results of CO2 Laser-assisted Deep Sclerectomy as Compared With Conventional Deep
      Sclerectomy.
AB  - PURPOSE: To evaluate the efficacy of CO2 laser-assisted sclerectomy surgery
      (CLASS) compared with classic nonpenetrating deep sclerectomy (NPDS) with implant
      in medically uncontrolled glaucoma patients. MATERIALS AND METHODS: Patients who
      underwent primary filtration surgery with CO2 laser system at the time interval
      between July 2010 and April 2011 were identified, their medical files were
      reviewed, and their results were compared with matched control group who
      underwent classic NPDS with intrascleral implant at the same time period.
      Intraocular pressure (IOP) was measured at baseline, 1 week, and 3, 6, 12, 18,
      and 24 months, respectively. Main outcome measures were: IOP, use of supplemental
      medical therapy, and failure (5 mm Hg>IOP>18 mm Hg, reoperation for glaucoma, or
      loss of light perception). RESULTS: A total of 58 patients were reviewed,
      including 27 in the CLASS group and 31 in the NPDS group. For the CLASS group the
      follow-up (mean+/-SD) was 20.7+/-6.8 months, the mean preoperative IOP was 23.3+/
      8.2 mm Hg (range, 10 to 38 mm Hg), and the mean number of antiglaucoma medication
      before surgery was 3.0+/-1.0 (range, 1 to 4). At final follow-up visits, the mean
      IOP was 11.7+/-3.1 mm Hg (range, 6 to 19 mm Hg), and the mean number of
      antiglaucoma medication was reduced to 1.0+/-1.6 (P<0.0003). The complete success
      rate (IOP<=18 mm Hg without antiglaucoma medication) was 73% and the qualified
      success rate (IOP<=18 mm Hg with/without antiglaucoma medication) was 96%. For
      the control group the mean follow-up was 17.6+/-6.7 months, the mean preoperative
      IOP was 23.1+/-7.3 mm Hg (range, 14 to 44 mm Hg), and the mean number of
      antiglaucoma medication before surgery was 3.0+/-0.8 (range, 1 to 4). At final
      follow-up visits, the IOP was 13.3+/-3.6 mm Hg (range, 8 to 20 mm Hg), and the
      mean number of antiglaucoma medication was reduced to 0.7+/-1.1 (P<0.0004). The
      complete success rate and the qualified success rate were 71% and 89%,
      respectively. CONCLUSIONS: A new technique using a CO2-laser ablation system
      allows precise and easy creation of the scleral space and ablation of Schlemm
      canal. This technique has been shown to be as efficient as the standard NPDS
      surgery in terms of IOP-lowering effect. This would render the deep sclerectomy
      an easier glaucoma surgery.

PMID- 25383471
TI  - Unprecedented synthesis of aza-bridged benzodioxepine derivatives through a
      tandem Rh(II)-catalyzed 1,3-rearrangement/[3+2] cycloaddition of
      carbonyltriazoles.
AB  - Rh(II)-catalyzed novel tandem intramolecular cycloisomerizations of aldehydes or
      ketones with 1-sulfonyl 1,2,3-triazoles have been disclosed, providing a facile
      protocol to access a series of functionalized aza-bridged benzodioxepine
      heterocycles.

PMID- 25383472
TI  - Generalization effects in Canadian and Chinese adults' simple addition.
AB  - Recent studies proposed that skilled adults solve simple addition problems (e.g.,
      2 + 3 = 5) by automatic counting procedures rather than fact retrieval for
      memory. To pursue this, the authors tested 36 Canadian and 36 Chinese adults in
      an addition paradigm designed to measure generalization of practice, a potential
      signature of procedure use. A generalization effect in response time occurred for
      rule-based 0 + N problems (e.g., practicing 0 + 3 facilitated subsequent
      performance of 0 + 7) for both Chinese and Canadian adults. No such effect
      occurred for other problem types including 1 + N problems, ties (e.g., 2 + 2),
      small nontie (sum <=10) or large nontie (sum >10). Thus, there was no evidence
      that Chinese or Canadian adults engaged a common procedural algorithm for nonzero
      simple addition.

PMID- 25383473
TI  - Maintaining information in visual working memory: Memory for bindings and memory
      for features are equally disrupted by increased attentional demands.
AB  - This study examined the role of attention in maintaining information between
      visual features in visual working memory. In a change detection paradigm, two
      different memory conditions were created: one that required the maintenance of
      features and one that required the maintenance of how the features were bound
      together. During the short retention interval that separated the study display
      and test display, a tone discrimination task was to be performed. The attentional
      demand of the tone discrimination task was manipulated to test whether memory for
      binding was more disrupted than memory for features when the proportion of time
      during which attention is unavailable for maintenance is increased. We observed
      that memory for features and memory for bindings were equally disrupted by
      increasing the attentional demands of the tone discrimination task. This suggests
      that attention does not play a special role in the maintenance of feature
      bindings in visual working memory.

PMID- 25383474
TI  - Category exemplars normed in Canada.
AB  - Normative data on category exemplar generation are widely used by psychologists
      but vary across cultures such that well-known norm sets developed in the United
      States might not be appropriate for use in Canada. To date, no published set of
      category exemplars has been normed with a Canadian undergraduate population. We
      describe the creation of such a set using the popular Battig and Montague (1969)
      categories and provide a link to the full set of norms.

PMID- 25383476
TI  - Phonological processing dynamics in bilingual word naming.
AB  - The current study investigated phonological processing dynamics in bilingual word
      naming. English-French and French-English bilinguals named interlingual
      heterophonic homographs (i.e., words that share orthography but not meaning or
      pronunciation across languages), heterophonic cognates (i.e., words that share
      both orthography and meaning across languages, but not pronunciations),
      interlingual homophones (i.e., words that share pronunciation, but not
      orthography or meaning across languages), and single-language matched control
      words in both English and French naming tasks. Cross-language phonological
      activation was strongest in bilinguals' second language. The results provided
      evidence for feedforward activation of phonological representations in the
      nontarget language, as well as feedback activation of these phonological
      representations from semantic representations. Results are interpreted within the
      more recent Bilingual Interactive Activation (BIA+) framework.

PMID- 25383477
TI  - Bivalent task switching and memory load: Similar costs on reaction times,
      different costs on concurrent timing.
AB  - Some studies suggest that time estimation involves executive control resources.
      This proposition was challenged recently, however, by results showing
      simultaneous performance of executive and timing tasks with no cost. The present
      study examined whether bivalent switching, in which targets may be relevant in
      more than one task, would interfere with timing. In Experiment 1, the effect of
      switching between memory search and a classification task was compared with the
      effect of varying load in memory search. Effects of task switching and of
      increasing load were similar on reaction times (RTs) in an RT control condition,
      but drastically different on concurrent timing: Time productions were affected by
      memory search only. In Experiment 2, the effect of task switching preparation,
      which involves advance reconfiguration in the switching paradigm, was examined.
      Preparation to a switch and timing could be performed simultaneously with no
      cost. These results reveal a fundamental difference between memory search and
      task switching in terms of dual-task costs, and show that timing and some
      executive control tasks do not share cognitive resources.

PMID- 25383478
TI  - From Brown-Peterson to continual distractor via operation span: A SIMPLE account
      of complex span.
AB  - Three memory tasks-Brown-Peterson, complex span, and continual distractor-all
      alternate presentation of a to-be-remembered item and a distractor activity, but
      each task is associated with a different memory system, short-term memory,
      working memory, and long-term memory, respectively. SIMPLE, a relative local
      distinctiveness model, has previously been fit to data from both the Brown
      Peterson and continual distractor tasks; here we use the same version of the
      model to fit data from a complex span task. Despite the many differences between
      the tasks, including unpredictable list length, SIMPLE fit the data well. Because
      SIMPLE posits a single memory system, these results constitute yet another
      demonstration that performance on tasks originally thought to tap different
      memory systems can be explained without invoking multiple memory systems.

PMID- 25383479
TI  - "I never forget a face, but in your case I'll be glad to make an exception":
      Intentional forgetting of emotional faces.
AB  - The current study used the item-method directed forgetting paradigm to determine
      whether there are limits on the ability to intentionally forget angry faces.
      During the study phase, faces were presented, 1 at a time, each followed by an
      instruction to remember or forget. Following the presentation of all faces,
      participants performed a yes-no recognition test. In 2 experiments that varied
      only the presentation duration of the face (500 ms vs. 1,000 ms), we observed an
      overall directed forgetting effect, with greater recognition of faces studied
      with remember rather than forget instructions; the magnitude of this effect did
      not vary with emotional expression. We interpret these results in light of the
      proposal that priority processing of angry faces benefits the speed of forming an
      enduring long-term memory trace rather than increasing the strength of that
      trace.

PMID- 25383480
TI  - Solvent structuring and its effect on the polymer structure and processability:
      the case of water-acetone poly-epsilon-caprolactone mixtures.
AB  - One of the most common processes to produce polymer nanoparticles is the solvent
      displacement method, in which the polymer is dissolved in a "good" solvent and
      the solution is then mixed with an "anti-solvent". The polymer processability is
      therefore determined by its structural and transport properties in solutions of
      the pure solvents and at the intermediate compositions. In this work, we focus on
      poly-epsilon-caprolactone (PCL) which is a biocompatible polymer that finds
      widespread application in the pharmaceutical and biomedical fields, performing
      full atomistic molecular dynamics simulations of one PCL chain of different
      molecular weight in a solution of pure acetone (good solvent), of pure water
      (antisolvent), and their mixtures. Our simulations reveal that the
      nanostructuring of one of the solvents in the mixture leads to an unexpected
      identical polymer structure irrespectively of the concentration of the two
      solvents. In particular, although in pure solvents the behavior of the polymer
      is, as expected, very different, at intermediate compositions, the PCL chain
      shows properties very similar to those found in pure acetone as a result of the
      clustering of the acetone molecules in the vicinity of the polymer chain. We
      derive an analytical expression to predict the polymer structural properties in
      solution at different solvent compositions and show that the solvent clustering
      affects in an unpredictable way the polymer diffusion coefficient. These findings
      have important consequences on the optimization of the nanoparticle production
      process and in the implementation of continuum modeling techniques to model it. 

PMID- 25383481
TI  - Auranofin, an anti-rheumatic gold compound, modulates apoptosis by elevating the
      intracellular calcium concentration ([ca2+]I) in mcf-7 breast cancer cells.
AB  - Auranofin, a transition metal complex is used for the treatment of rheumatoid
      arthritis but is also an effective anti-cancer drug. We investigate the effects
      of Auranofin in inducing cell death by apoptosis and whether these changes are
      correlated to changes of intracellular calcium concentration ([Ca2+]i) in breast
      cancer cells (MCF-7). Cytotoxicity of Auranofin was evaluated using MTS assay and
      the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD
      apoptotic death and necrotic death were differentiated by Flow cytometry. A
      concentration dependent decrease in the viability occurred and cells were shifted
      to the apoptotic phase. Intracellular calcium ([Ca2+]i) was recorded using
      florescence microscopy and a calcium sensitive dye (Fluo-4 AM) with a strong
      negative correlation (r = -0.713) to viability. Pharmacological modulators 2-APB
      (50 MUM), Nimodipine (10 MUM), Caffeine (10 mM), SKF 96365(20 MUM) were used to
      modify calcium entry and release. Auranofin induced a sustained increase of
      [Ca2+]i in a concentration and time dependent manner. The use of different
      blockers of calcium channels did not reveal the source for the rise of [Ca2+]i.
      Overall, elevation of [Ca2+]i by Auranofin might be crucial for triggering Ca2+
      dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating
      [Ca2+]i should be considered as a crucial factor for the induction of cell death
      in cancer cells. 

PMID- 25383483
TI  - Bridging the gap between neurocognitive processing theory and performance
      validity assessment among the cognitively impaired: a review and methodological
      approach.
AB  - Bigler (2012) and Larrabee (2012) recently addressed the state of the science
      surrounding performance validity tests (PVTs) in a dialogue highlighting evidence
      for the valid and increased use of PVTs, but also for unresolved problems.
      Specifically, Bigler criticized the lack of guidance from neurocognitive
      processing theory in the PVT literature. For example, individual PVTs have
      applied the simultaneous forced-choice methodology using a variety of test
      characteristics (e.g., word vs. picture stimuli) with known neurocognitive
      processing implications (e.g., the "picture superiority effect"). However, the
      influence of such variations on classification accuracy has been inadequately
      evaluated, particularly among cognitively impaired individuals. The current
      review places the PVT literature in the context of neurocognitive processing
      theory, and identifies potential methodological factors to account for the
      significant variability we identified in classification accuracy across current
      PVTs. We subsequently evaluated the utility of a well-known cognitive
      manipulation to provide a Clinical Analogue Methodology (CAM), that is, to alter
      the PVT performance of healthy individuals to be similar to that of a cognitively
      impaired group. Initial support was found, suggesting the CAM may be useful
      alongside other approaches (analogue malingering methodology) for the systematic
      evaluation of PVTs, particularly the influence of specific neurocognitive
      processing components on performance.

PMID- 25383486
TI  - Radical-triplet pair mechanism of electron spin polarization. Detailed
      theoretical treatment.
AB  - Specific features of net chemically induced dynamic electron spin polarization
      (CIDEP) P(n), generated in liquid-phase triplet-radical (TR) quenching, are
      analyzed in detail within the general model, which allows for fairly simple
      analysis of CIDEP both numerically and analytically. This model enables one to
      accurately treat nonadiabatic transitions between the terms of TR-pair spin
      Hamiltonian, resulting in CIDEP generation. The proposed theory predicts fairly
      simple analytical dependence of P(n) on parameters of the model. In particular,
      it is shown that within the wide region of parameters the P(n) dependence on the
      coefficient of relative TR diffusion D(r) is described by simple linear relation
      P(n)(-1)(D(r)) ~ Q0 + q(n)D(r) (Q0 and q(n) are independent of D(r)). It is also
      demonstrated that obtained numerical and analytical results are very helpful for
      the analysis of experimental data, which is demonstrated by analyzing the
      experimental D(r)-dependence of P(n).

PMID- 25383482
TI  - Occurrence, source, and human infection potential of Cryptosporidium and
      Enterocytozoon bieneusi in drinking source water in Shanghai, China, during a pig
      carcass disposal incident.
AB  - In March 2013, thousands of domestic pig carcasses were found floating in the
      Huangpu River, a drinking source water in Shanghai, China. To investigate the
      impact of the pig carcass incident on microbial water quality, 178 river water
      samples were collected from the upper Huangpu River from March 2013 to March
      2014. Samples were concentrated by calcium carbonate flocculation and examined
      for host-adapted Cryptosporidium and Enterocytozoon bieneusi by ploymerase chain
      reaction (PCR). Positive PCR products were sequenced to determine Cryptosporidium
      species and E. bieneusi genotypes. A total of 67 (37.6%) and 56 (31.5%) samples
      were PCR-positive for Cryptosporidium and E. bieneusi, respectively. The
      occurrence rates of Cryptosporidium and E. bieneusi in March 2013 (83.3%; 41.7%)
      and May 2013 (73.5%; 44.1%) were significantly higher than rates in later
      sampling times. Among the 13 Cryptosporidium species/genotypes identified, C.
      andersoni and C. suis were the most common species, being found in 38 and 27
      samples, respectively. Seventeen E. bieneusi genotypes were found, belonging to
      11 established genotypes (EbpC, EbpA, D, CS-8, PtEb IX, Peru 8, Peru 11,
      PigEBITS4, EbpB, G, O) and six new ones (RWSH1 to RWSH6), most of which belonged
      to pig-adapted Groups 1d and 1e. EbpC was the most common genotype, being found
      in 37 samples. The distribution of Cryptosporidium species and E. bieneusi
      genotypes suggest that dead pigs contributed significantly to Cryptosporidium and
      E. bieneusi contamination in the Huangpu River. Although most Cryptosporidium
      species found in river water were not major human pathogens, the majority of E.
      bieneusi genotypes detected were endemic in China. Data from this study should be
      useful in the development of strategies in addressing future contamination events
      in drinking water supplies. 

PMID- 25383487
TI  - Structural, spectroscopic, and magnetic properties of Eu3+-doped GdVO4
      nanocrystals synthesized by a hydrothermal method.
AB  - New interesting aspects of the spectroscopic properties, magnetism, and method of
      synthesis of gadolinium orthovanadates doped with Eu(3+) ions are discussed. Gd(1
      x)Eu(x)VO4 (x = 0, 0.05, 0.2) bifunctional luminescent materials with complex
      magnetic properties were synthesized by a microwave-assisted hydrothermal method.
      Products were formed in situ without previous precipitation. The crystal
      structures and morphologies of the obtained nanomaterials were analyzed by X-ray
      diffraction and transmission and scanning electron microscopy. Crystallographic
      data were analyzed using Rietveld refinement. The products obtained were
      nanocrystalline with average grain sizes of 70-80 nm. The qualitative and
      quantitative elemental composition as well as mapping of the nanocrystals was
      proved using energy-dispersive X-ray spectroscopy. The spectroscopic properties
      of red-emitting nanophosphors were characterized by their excitation and emission
      spectra and luminescence decays. Magnetic measurements were performed by means of
      vibrating sample magnetometry. GdVO4 and Gd0.8Eu0.2VO4 exhibited paramagnetic
      behavior with a weak influence of antiferromagnetic couplings between rare-earth
      ions. In the substituted sample, an additional magnetic contribution connected
      with the population of low-lying excited states of europium was observed.

PMID- 25383488
TI  - Development and application of methodology for rapid screening of potential
      amyloid probes.
AB  - Herein, we demonstrate that it is possible to rapidly screen hydrophobic
      fluorescent aromatic molecules with regards to their properties as amyloid
      probes. By grinding the hydrophobic molecule with the amyloidogenic protein
      insulin, we obtained a water-soluble composite material. When this material is
      dissolved and exposed to conditions promoting amyloid formation, the protein
      aggregates into amyloid fibrils incorporating the hydrophobic molecule. As a
      result, changes in the fluorescence spectra of the hydrophobic molecule can be
      correlated to the formation of amyloid fibrils, and the suitability of the
      hydrophobic molecular skeleton as an amyloid probe can thus be assessed. As a
      result, we discovered two new amyloid probes, of which one is the well-known
      laser dye DCM. The grinding method can also be used for rapid preparation of
      novel composite materials between dyes and proteins, which can be used in
      materials science applications such as organic electronics and photonics. 

PMID- 25383490
TI  - The effects of wild blueberry consumption on plasma markers and gene expression
      related to glucose metabolism in the obese Zucker rat.
AB  - Impaired fasting blood glucose is one of the landmark signs of metabolic
      syndrome, together with hyperinsulinemia, dyslipidemia, hypertension, and a
      chronic proinflammatory, pro-oxidative, and prothrombotic environment. This study
      investigates the effect of wild blueberry (WB) consumption on blood glucose
      levels and other parameters involved in glucose metabolism in the obese Zucker
      rat (OZR), an experimental model of metabolic syndrome. Sixteen OZRs and 16 lean
      littermate controls (lean Zucker rat [LZR]) were fed an 8% enriched WB diet or a
      control (C) diet for 8 weeks. Plasma concentrations of glucose, insulin, glycated
      hemoglobin GHbA1c, resistin, and retinol-binding protein 4 (RBP4) were measured.
      Expression of the resistin, RBP4, and glucose transporter GLUT4 genes was also
      determined both in the liver and the abdominal adipose tissue (AAT). Plasma
      glycated hemoglobin HbA1c, RBP4, and resistin concentrations were significantly
      lower in OZRs following the WB diet (-20%, -22%, and -27%, respectively, compared
      to C diet, P<.05). Following WB consumption, resistin expression was
      significantly downregulated in the liver of both OZRs and LZRs (-28% and -61%,
      respectively, P<.05), while RBP4 expression was significantly downregulated in
      the AAT of both OZRs and LZRs (-87% and -43%, respectively, P<.05). All other
      markers were not significantly affected following WB consumption. In conclusion,
      WB consumption normalizes some markers related to glucose metabolism in the OZR
      model of metabolic syndrome, but has no effect on fasting blood glucose or
      insulin concentrations. 

PMID- 25383489
TI  - The management of cognitive impairment in bipolar disorder: current status and
      perspectives.
AB  - Bipolar disorder (BD) is associated with important cognitive deficits that
      persist during the periods of remission. Although these deficits seem to play an
      important role in the functional impairment experienced by bipolar patients,
      evidence regarding their clinical management is scant. We revised the databases
      PubMed, MEDLINE, and clinicaltrials.gov, searching for studies focusing on the
      pharmacological and nonpharmacological treatment of cognitive deficits among
      bipolar patients. In addition, a manual search of bibliographical cross
      references was performed. Currently, there is no Food and Drug Administration
      approved pharmacological agent for the management of cognitive deficits in BD. A
      number of agents have been tested in the treatment of cognitive deficits in BD,
      with mixed results. Nonpharmacological interventions, such as cognitive
      remediation and noninvasive brain stimulation techniques, seem promising, but
      their role has not yet been properly explored among bipolar patients. Additional
      studies, aiming at evaluating the efficacy of interventions combining cognitive
      rehabilitation and biological treatments, are highly desirable. 

PMID- 25383491
TI  - [Physical activity and sedentary lifestyle: family and socio-demographic
      determinants and their impact on adolescents' health].
AB  - OBJECTIVE: Estimating whether adolescents' sedentary behaviour and their lack of
      physical activity is determined by family characteristics or socio-cultural
      aspects and their impact on health and adiposity level. MATERIAL AND METHODS: 932
      adolescents were surveyed. Information regarding physical activity, sedentary
      behaviour, anthropometric index and family characteristics (structure, dynamics
      and functioning) was estimated by adolescents answering a questionnaire. RESULTS:
      The sample's average age was 16.07+/-1.09 years old, 56.3 % were female, 66.3 %
      had a low level of physical activity and 51.9 % were sedentary. A lack of
      physical activity occurred more frequently in females (56.8 % cf 41.5 %:
      p=0.000); family characteristics did not influence such risk behaviour. A
      relationship between physical activity and sedentary lifestyle with BMI could not
      be demonstrated, whilst waist circumference was associated with risky behaviour
      patterns. Teenagers in good health were more active (36.1 % cf 27 %) and less
      sedentary (49.3 % cf 59.4 %) than those for whom an unhealthy state was reported.
      CONCLUSION: Sedentary behaviour and a lack of physical activity were more
      determined by socio-demographic factors than family aspects, such behaviour
      pattern having a direct influence on the adolescents' health.

PMID- 25383492
TI  - [The prevalence and types of bullying in 13 to 17 year-old Brazilian
      schoolchildren].
AB  - OBJECTIVE: Determining the prevalence and type of bullying in 13 to 17 year-old
      Brazilian schoolchildren and analyzing the associated factors. METHODS: Simple
      random sampling was used for selecting 525 schoolchildren. Data was collected by
      a single researcher using the Training and Mobility on Research (TMR) model
      questionnaire on bullying. Students who admitted suffering this kind of violence
      three or more times during the year the data was collected were considered as
      victims of bullying. The data was stored in SPSS and analysed using the Chi
      squared and Fisher's exact tests (p<0.05). RESULTS: The students' average age was
      14.2 years old (+/-1.1); 54.1 % of the sample was female. 23.6 % of those
      surveyed were characterized as victims of bullying; most were aged 14 years old
      (27.3 %), male (31.5 %), in the 7th year of school (25.3 %) and no difference was
      found regarding when they attended school (i.e. morning or afternoon sessions).
      However, an association was found between gender and bullying at school
      (p<0.001). The most prevalent form of bullying was verbal (87.7 %) followed by
      relational (37.7 %) and physical bullying (19.7 %). CONCLUSION: There was a high
      prevalence of bullying, boys being the main victims; the predominant type of
      bullying was verbal.

PMID- 25383493
TI  - [Obesity, hypertension, and socioeconomic status in western Santa Catarina,
      Brazil].
AB  - OBJECTIVE: This research was aimed at evaluating the relationship between
      obesity, socioeconomic status and high blood pressure (HBP) in volunteers living
      in western Santa Catarina, Brazil. MATERIALS AND METHODS: 955 volunteers were
      evaluated; 31 % were male (aged 51.0+/-12.8 years old a weighing 78.4+/-13.6 kg)
      and 69 % female (aged 50.0+/-12.5 years old and weighing 69.8+/-13.4kg).
      Individuals having >=140 mmHg systolic blood pressures (SBP) and >= 90 mmHg
      diastolic blood pressures (DBP) were classified as being hypertensive and those
      having >= 30 kg/m2 body mass index (BMI) as being obese. RESULTS: HBP prevalence
      in this study was 35.1 % among males and 29.4 % in women. The percentage of men
      classified as having borderline HBP was also higher than that for women (20.9 %
      cf 16.7 %); 25.7 % of HBP women and 34.6 % HBP males were overweight and 48.3 %
      HBP women and 56.9 % males were obese. HBP distribution regarding socioeconomic
      status (high, middle and low income) had greater variation amongst women (cero %,
      27.5 % and 37.3 %, respectively) than men (30.4 %, 36.2 % and 30.1 %,
      respectively). CONCLUSION: This study provided consistent evidence of obesity
      being associate with HBP. Although this fact is widely known, what should be
      taken into consideration here is HBP regarding BMI category; normal, overweight
      and obese volunteers differed substantially between the genders.

PMID- 25383494
TI  - [Validating mid-upper arm circumference (MUAC) measurement for detecting acute
      malnutrition in 6-59 month-old children in emergency and disaster situations].
AB  - OBJECTIVES: Validating the results of mid-upper arm circumference (MUAC)
      measurement in 6-59 month-old children when MUAC was measured by community agents
      in areas where an emergency had been declared. Evaluating the cut-offs used for
      identifying children suffering from acute malnutrition in Colombia today.
      METHODOLOGY: Previously trained community agents and a nutritionist carried out a
      cross-sectional study for evaluating MUAC agreement, reproducibility and
      sensitivity in detecting acute malnutrition. Three hundred and six children were
      assessed in three municipalities where an emergency had been declared in the
      Cordoba department of Colombia. RESULTS: A Bland and Altman plot gave high
      agreement regarding measurements taken by the community agents and the
      nutritionist, 94 % of the measurements coming within the agreement limits. The
      intra-class correlation coefficient gave 0.87 reproducibility; however,
      validating the criterion for calculating the area below the ROC curve,
      sensitivity and the impact of the children's age on MUAC measurements highlighted
      problems in using 11.5 centimeters as the cut-off. CONCLUSIONS: MUAC measurement
      was reliable, had good reproducibility and led to rapid diagnosis of nourishment
      status in 6-59 month-old children living in areas where an emergency had been
      declared. Validating the criterion, sensitivity, the impact of the children's age
      on MUAC measurement results and improved nourishment status concerning children
      aged less than 5 years old in Colombia highlighted the need for changing the
      current cut-off and using 14 centimeters instead.

PMID- 25383495
TI  - The role of the neighborhood, family and peers regarding Colombian adolescents'
      social context and aggressive behavior.
AB  - OBJECTIVE: Examining neighborhood conditions, parenting and peer affiliations'
      association with adolescents' aggressive behavior. Testing various mechanisms
      through which neighborhood conditions influence two adolescent outcomes, both
      directly and indirectly (via their impact on parenting and peer-affiliation):
      aggression and delinquency. METHOD: Data regarding adolescents was taken from a
      self-reporting survey of 1,686 Colombian adolescents living in 103 neighborhoods
      of Medellin. Neighborhood-related data was taken from official government
      datasets, as well as two separate community surveys. Both multilevel modeling and
      multilevel structural equation modeling were used in the analysis. RESULTS: The
      probability of an adolescent engaging in aggression in Medellin was 7.0 % and
      becoming involved in delinquency 0.3 %. There was also significant variation for
      both forms of aggressive behavior at neighborhood-level (7.0 % aggression and 14
      % regarding the delinquency scale). No neighborhood condition had a direct
      association with adolescents' aggressive behavior; however; the neighborhood
      exerted an indirect influence on adolescent behavior which was mainly transmitted
      through families and the quality of friends within a particular community.
      CONCLUSIONS: Residing in disadvantaged neighborhoods did have an adverse effect
      on adolescents' aggressive behavior, mainly because of a lack of effective
      parenting strategies thereby facilitating affiliations being made with deviant
      peers. More efficient intervention for reducing adolescents' aggressive behavior
      should thus target areas having high odds of aggressive behavior and focus on
      improving community resources and, more importantly, on controlling adolescent
      peer groups, the lack of parental monitoring and inconsistent discipline.

PMID- 25383496
TI  - [Elementary school teachers and their quality of life].
AB  - OBJECTIVES: Investigating some pertinent factors associated with elementary
      education teachers' quality of life working in the Brazilian city of
      Florianopolis and surrounding district. METHODS: 349 state and municipal school
      system elementary school teachers working in the city and its surrounding areas
      answered a questionnaire containing work-related questions and the WHO Quality of
      Life-BREF (WHOQOL-BREF) questionnaire. Descriptive statistics were used and the
      differences between means were analyzed, considering physical, psychological,
      social relationships and environmental domains. RESULTS: Teachers working more
      hours per week and in the state school system had lower quality of life indices
      in all domains investigated. Those having more years of service in the teaching
      profession had lower quality of life indexes regarding the physical (p=0.007) and
      social relationships (p<0.001) domains. Teachers occupying management/supervisory
      posts had higher quality of life scores in the environmental domain compared to
      classroom teachers. CONCLUSIONS: The hours worked seemed to be the main factor
      associated with lower quality of life scores in this sample of elementary school
      teachers.

PMID- 25383497
TI  - [Accreditation standards concerning patients' rights: a review of the current
      state of affairs related to drug-addiction treatment centers in Colombia].
AB  - OBJECTIVE: Characterizing and contrasting the current state of affairs concerning
      patients' rights-associated accreditation standards in a sample of drug-addiction
      treatment centers in Colombia. METHODS: This was mixed methodology research (i.e.
      descriptive and hermeneutic); a pilot sample of 21 drug-addiction treatment
      centers in Colombia was used for determining the current state of patients'
      rights accreditation standards. The possible relationship or independence between
      categorical variables was evaluated by using Fisher's exact test (0.05
      significance level). A contrasting documentary review was made at the same time.
      RESULTS: Drug-addiction treatment centers provided more information for families
      (95 %) than patients (90 %) or minors (81 %). Possible barriers to gaining access
      for treatment were being HIV positive (29 %), being part of the LGTB population
      (14 %) and being female (10 %); religion and ethnicity were not seen as grounds
      for discrimination or treatment barriers. The patients' rights standards group
      coincided with Colombia's accreditation system and Joint Commission standards;
      however, the latter accreditation entity has made significant progress regarding
      a specific manual for drug-addiction treatment centers. CONCLUSIONS: The centers
      assessed in Colombia had made advances regarding accrediting patients' rights,
      but such standards require revision for being adapted to international
      developments and specific matters involved in treating addicts and the specific
      conditions for institutions dealing with such treatment.

PMID- 25383498
TI  - [Factors correlated with low-income diabetic patients' quality of life in
      Bogota].
AB  - OBJECTIVE: Identifying the factors correlated with health-related quality of life
      (QOL) amongst low-income diabetic patients attending two public hospitals in
      Bogota. METHODS: This was a cross-sectional study involving 153 type 2 diabetic
      patients. The variables studied were socio-demographic characteristics, social
      support, lifestyle and clinical measurements (HbA1c, BMI, and cholesterol). The
      SF-8 health survey (8-item short form) was used for assessing health-related QOL.
      RESULTS: Overall physical score was 41.4 (SE 8.5) and overall mental score 46.5
      (SE 7.3); the scores never exceeded 50 points. The factors correlated with lower
      QOL regarding the physical domain were occupation, social support, physical
      activity and fat intake and age, occupation, social support, and smoking status
      regarding the mental domain. CONCLUSIONS: The patients surveyed here had a poor
      QOL. The factors correlated with health-related QOL included socio-demographic
      characteristics, social support and lifestyle. These findings should be taken
      into account when formulating public health policy to readdress the current
      healthcare model for controlling diabetes.

PMID- 25383499
TI  - [18FDG-PET/CT cost-effectiveness compared to CT at the end of treatment in
      pediatric Hodgkin's lymphoma patients].
AB  - OBJECTIVE: Estimating the cost-effectiveness of 18FDG-PET/CT (positron emission
      tomography) compared to computer tomography (CT) followed by 18FDG-PET/CT as a
      confirmatory test for a positive case at the end of treatment in Hodgkin's
      lymphoma (HL) patients under 18 years-old. METHODS: A decision tree was built for
      comparing 18FDG-PET/CT to CT followed by 18FDG-PET/CT as a confirmatory test for
      a positive case in detecting residual lesions; outcome was measured in life years
      gained (LYG). The cost-effectiveness ratio was calculated; the threshold was 3
      times the per capita GDP per LYG. Values were expressed in Colombian pesos for
      2010 (1 US dollar=$ 1,897.89) and submitted to deterministic and probabilistic
      sensitivity analysis. RESULTS: Assuming a difference of 13 months in true
      positives' life expectancy compared to that for false negatives, the cost of an
      additional LYG with 18FDG-PET/CT compared to CT followed by 18FDG-PET/CT as a
      confirmatory test for a positive case when evaluating the end of pediatric HL
      patients' treatment was $ 34,508,590 (COP). CONCLUSION: If differential life
      expectancy between true positives and false negatives is at least 1.03 years,
      then using 18FDG-PET/CT for evaluating the end of HL pediatric patients' therapy
      is a cost-effective strategy for Colombia.

PMID- 25383500
TI  - ErbB2+ metastatic breast cancer treatment after progression on trastuzumab: a
      cost-effectiveness analysis for a developing country.
AB  - OBJECTIVE: Breast cancer (BC) and metastatic breast cancer (MBC) are significant
      causes of deaths amongst women worldwide, including developing countries. The
      cost of treatment in the latter is even more of an issue than in higher income
      countries. ErbB2 overexpression is a marker of poor prognosis and the goal for
      targeted therapy. This study was aimed at evaluating the cost-effectiveness in
      Colombia of ErbB2+ MBC treatment after progression on trastuzumab. METHODS: A
      decision analytic model was constructed for evaluating such treatment in a
      hypothetical cohort of ErbB2+MBC patients who progressed after a first scheme
      involving trastuzumab. The alternatives compared were lapatinib+capecitabine
      (L+C), and trastuzumab+a chemotherapy agent (capecitabine, vinorelbine or a
      taxane). Markov models were used for calculating progression-free time and the
      associated costs. Effectiveness estimators for such therapy were identified from
      primary studies; all direct medical costs based on national fees-guidelines were
      included. Sensitivity was analyzed and acceptability curves estimated. A 3 %
      discount rate and third-payer perspective were used within a 5-year horizon.
      RESULTS: L+C dominated its comparators. Its cost-effectiveness ratio was COP
      $49,725,045 per progression-free year. The factors most influencing the results
      were the alternatives' hazard ratios and the cost of trastuzumab. CONCLUSION:
      Lapatinib was cost-effective compared to its alternatives for treating MBC after
      progression on trastuzumab using a Colombian decision analytic model.

PMID- 25383501
TI  - [Knowledge, attitudes and practice regarding dengue in a neighborhood forming
      part of the city of Cartagena].
AB  - OBJECTIVE: Identifying attitudes, practice and knowledge regarding dengue in a
      neighborhood of the city of Cartagena. METHODS: This was a cross-sectional study
      of 870 people living in a neighborhood in the south-eastern part of Cartagena.
      Probabilistic, randomized, three-staged sampling was used; it was intended to
      ascertain attitudes, practice and knowledge about dengue. The Stata statistics
      package (version 11.1) was used for analyzing the data to determine the absolute
      and relative frequency for each variable studied. RESULTS: It was found that 93.7
      % of those surveyed knew about the disease; although 49.7 % did not know what the
      causal agent of the disease was, 80.5 % of those surveyed did express an
      interest. In receiving health education classes. 60.1 % of the population
      surveyed here stored water in their homes and 73.8 % used tanks as containers.
      24.8 % of those surveyed stated that they avoided having/using stagnant water.
      CONCLUSIONS: The residents confirmed the high incidence of dengue cases reported
      by the district health department. Knowledge about dengue was limited; risky
      practices favoring the disease's development were adopted, but an attitude
      towards controlling this issue was evident. Changes in current behavior patterns
      must thus be promoted in the community and also regarding how prevention and
      control programs are being carried out.

PMID- 25383502
TI  - [The influence of climate and vegetation cover on the occurrence of dengue cases
      (2001-2010)].
AB  - OBJECTIVE: Analyzing the spatio-temporal relationship regarding the occurrence of
      cases of dengue in Colombia's Cordoba Department and the temperature, rainfall
      and the phenological state of vegetation (vigor and density). METHODS: A
      statistical and cartographical study of spatio-temporal distribution regarding
      the occurrence of cases of dengue was studied in 30 selected municipalities.
      Simple and multiple statistical regressions were used for analyzing disease
      occurrence and the aforementioned climatic variables. The statistical
      relationship between dengue cases and the normalized difference vegetation index
      (NDVI) was calculated using satellite images. A linear multiple relationship
      between the occurrence of dengue cases and temperature, rainfall and NDVI was
      calculated. RESULTS: Accordingly to the pertinent cartography, the disease
      extends over 32 % of the department; 89.7 % of the reported cases of dengue
      occurred in 13 of the 22 selected municipalities, Monteria being the municipality
      having the greatest occurrence (37.8 %). Analysis and evaluation of the
      statistical regressions showed that the selected climatic variables and
      vegetation state were significantly related to the occurrence of dengue, both
      separately and simultaneously. CONCLUSIONS: The statistical validity of the
      relationships calculated between the variables studied here supported the
      conclusion that an increase in the occurrence of cases of dengue was also
      directly related to a simultaneous increase in temperature, decreased rainfall
      and deterioration of vegetation cover (vigor and density) in the area being
      studied.

PMID- 25383503
TI  - [Health promotion: the evolution of a paradigm and contemporary challenges].
AB  - The public health movement and the subsequent changes accompanying it have
      changed the way problems affecting populations' is understood and/or addressed
      within their contexts. This article aimed to analyze health promotion
      contemporaneity, examining its evolution as a discipline and the current
      challenges it faces. The evolution of health promotion led to consolidating a set
      of principles, such as those concerned with socio-ecological and salutogenic
      perspectives, a holistic, multi-sector approach, a concern for sustainable
      development, a commitment to social justice and equity, a participatory approach
      to individual and community capacity-building and respect and sensitivity
      regarding cultural diversity. The limitations of traditional models of research,
      a concern for social inequality regarding health and new global health challenges
      have raised the need for more comprehensive perspectives concerning research and
      intervention. Several research approaches' complementarity has been evaluated to
      better understand the processes and factors underlying complex health issues
      (i.e. quantitative and qualitative studies and community-based participatory
      research). Such knowledge fuels the planning of policy and interventions tailored
      to population needs which have been adopted in a collaborative, multi-sector
      approach and which are more effective in addressing global health's fresh
      challenges. Health promotion (as a dynamic discipline) has evolved in response to
      health issues arising in today's globalized world; yet developing its fields of
      theory, research and action is a continuing need. 

PMID- 25383504
TI  - Hierarchical nanoporous glass with antireflectivity and superhydrophilicity by
      one-pot etching.
AB  - We have developed a hierarchical nanoporous layer (HNL) on silicate glass by a
      simple one-pot etching method. The HNL has a three-dimensionally continuous
      spongelike structure with a pore size of a few tens of nanometers on its apparent
      surface. The pore size gradually decreases from the apparent surface to the HNL
      bulk interface. This HNL bestows significant properties to glass: low optical
      reflectivity that reflects 7% less visible light than nontreated glass and long
      persistence superhydrophilicity that keeps its water contact angle at about 5
      degrees  for more than 1 year. The superhydrophilicity also realizes antifogging
      and antifouling functionalities. 

PMID- 25383505
TI  - Understanding thermal phases in atomic detail by all-atom molecular-dynamics
      simulation of a phospholipid bilayer.
AB  - All-atom molecular dynamics (MD) simulations were used to investigate the thermal
      phase behavior of two hydrated phospholipids, namely, DPPC and DPPE, at the
      atomic level. The trajectories in the MD simulations clearly identified the
      structures of DPPC in the crystalline (Lc), gel (Lbeta), ripple (Pbeta), and
      liquid-crystalline (Lalpha) phases and those of DPPE in the Lc and Lalpha phases.
      The physicochemical and structural properties of these phases agree well with the
      experimental results. Moreover, the structural transformations between phases
      were observed. In the Lbeta phase, forces are directed in opposite directions in
      the upper and lower layers of the bilayer. These forces, which are due to the
      thermal motion of each monolayer, strongly influence the series of phase
      transitions from Lbeta to Pbeta. The MD simulations in this work can provide an
      understanding of the dynamics of the lipid bilayer in each thermal phase and
      suggest the mechanism that generates the Pbeta phase. 

PMID- 25383506
TI  - "AND" logic gate regulated pH and reduction dual-responsive prodrug nanoparticles
      for efficient intracellular anticancer drug delivery.
AB  - A dual-responsive drug delivery system simulating an AND logic gate is developed
      by core-cross-linking of a disulfide-containing anticancer prodrug with Cu(2+)
      for safe and efficient delivery of anticancer drugs. These prodrug nanoparticles
      are stable and exhibit nearly no premature drug release, and allow a fast drug
      release under simulated intracellular conditions, realizing a precise drug
      delivery towards cell nuclei. 

PMID- 25383508
TI  - Fertility sparing management and pregnancy in patients with granulosa cell tumour
      of the ovaries.
AB  - Granulosa cell tumours (GCTs) of the ovary are a rare entity among the neoplasms
      of gynaecological oncology. Deriving from the stroma of the ovary, GCTs are
      generally characterised by insidious growth, low malignancy potential and late
      recurrence. The standard treatment for these tumours is principally surgical,
      consisting of bilateral adnexectomy and hysterectomy. This is a narrative review
      of the current literature regarding the role of fertility sparing surgery in
      ovarian granulosa tumour. In the included studies, fertility sparing surgery was
      performed in 171 out of 350 patients. Recurrence rates ranged between 9.8-27.4%.
      Out of 131 patients, 15 achieved pregnancy. The data were limited regarding
      completion post-pregnancy surgery. Due to the fact that GCTs often affect younger
      ages, of crucial importance is the preservation of fertility by conserving the
      uterus and the contralateral ovary, while close monitoring is essential in order
      to achieve early identification and treatment of a possible recurrence. After
      completion of family planning, hysterectomy and salpingo-oophorectomy are
      recommended. 

PMID- 25383509
TI  - Comparing the biological washout of beta+-activity induced in mice brain after
      12C-ion and proton irradiation.
AB  - In clinical ion beam therapy, protons as well as heavier ions such as carbon are
      used for treatment. For protons, beta(+)-emitters are only induced by
      fragmentation reactions in the target (target fragmentation), whereas for heavy
      ions, they are additionally induced by fragmentations of the projectile (further
      referred to as autoactivation). An approach utilizing these processes for
      treatment verification, by comparing measured Positron Emission Tomography (PET)
      data to predictions from Monte Carlo simulations, has already been clinically
      implemented. For an accurate simulation, it is important to consider the
      biological washout of beta(+)-emitters due to vital functions. To date,
      mathematical expressions for washout have mainly been determined by using
      radioactive beams of (10)C- and (11)C-ions, both beta(+)-emitters, to enhance the
      counting statistics in the irradiated area. Still, the question of how the choice
      of projectile (autoactivating or non-autoactivating) influences the washout
      coefficients, has not been addressed. In this context, an experiment was carried
      out at the Heidelberg Ion Beam Therapy Center with the purpose of directly
      comparing irradiation-induced biological washout coefficients in mice for protons
      and (12)C-ions. To this aim, mice were irradiated in the brain region with
      protons and (12)C-ions and measured after irradiation with a PET/CT scanner
      (Siemens Biograph mCT). After an appropriate waiting time, the mice were
      sacrificed, then irradiated and measured again under similar conditions. The
      resulting data were processed and fitted numerically to deduce the main washout
      parameters. Despite the very low PET counting statistics, a consistent difference
      could be identified between (12)C-ion and proton irradiated mice, with the (12)C
      data being described best by a two component fit with a combined medium and slow
      washout fraction of 0.50 +/- 0.05 and the proton mice data being described best
      by a one component fit with only one (slow) washout fraction of 0.73 +/- 0.06.

PMID- 25383510
TI  - In search of evidence-based treatment for concussion: characteristics of current
      clinical trials.
AB  - Abstract Objective: To assess the characteristics of current clinical trials
      investigating the treatment of concussion. BACKGROUND: Recent systematic
      literature reviews have concluded that there is minimal evidence to support any
      specific treatment for concussion, including the principles of return-to-activity
      protocols such as type or duration of rest. DESIGN/METHODS: Clinical trial data
      was extracted from Clinicaltrials.gov and seven additional World Health
      Organization primary registries. The trial databases were accessed up until 3
      October 2013. This study used search terms of 'concussion' or 'mild traumatic
      brain injury' (mTBI) and filtered for interventional trials. Trials that were
      terminated, already published or not interventional trials of concussion/mTBI
      were excluded. RESULTS: Of the 142 concussion/mTBI interventional clinical trials
      identified, 71 met inclusion criteria. Trials had a median estimated enrolment of
      60 participants. There was a wide-range of treatments studied, including
      cognitive/behavioural therapies (28.2%), medications (28.2%), devices (11.3%),
      dietary supplements (8.5%), return-to-activity/rest (1.4%) and others (22.4%).
      Heterogeneity among trials for concussion identification/diagnosis and primary
      outcomes utilized was evident. Symptom-based questionnaires (39.4%) and
      neuropsychological tests (28.2%) were the most common outcome measures.
      CONCLUSIONS: Diverse, potentially promising therapeutics are currently being
      studied for the treatment of concussion. However, several deficiencies were
      identified including a paucity of trials addressing return-to-activity
      principles. Also, small sample size and trial heterogeneity may threaten
      scientific evaluation and subsequent clinical application.

PMID- 25383511
TI  - Batteries: Knowing when small is better.

PMID- 25383512
TI  - Magnonic charge pumping via spin-orbit coupling.
AB  - The interplay between spin, charge and orbital degrees of freedom has led to the
      development of spintronic devices such as spin-torque oscillators and spin
      transfer torque magnetic random-access memories. In this development, spin
      pumping represents a convenient way to electrically detect magnetization
      dynamics. The effect originates from direct conversion of low-energy quantized
      spin waves in the magnet, known as magnons, into a flow of spins from the
      precessing magnet to adjacent leads. In this case, a secondary spin-charge
      conversion element, such as heavy metals with large spin Hall angle or multilayer
      layouts, is required to convert the spin current into a charge signal. Here, we
      report the experimental observation of charge pumping in which a precessing
      ferromagnet pumps a charge current, demonstrating direct conversion of magnons
      into high-frequency currents via the relativistic spin-orbit interaction. The
      generated electric current, unlike spin currents generated by spin-pumping, can
      be directly detected without the need of any additional spin-charge conversion
      mechanism. The charge-pumping phenomenon is generic and gives a deeper
      understanding of its reciprocal effect, the spin orbit torque, which is currently
      attracting interest for their potential in manipulating magnetic information. 

PMID- 25383513
TI  - Spin orbitronics: Charges ride the spin wave.

PMID- 25383514
TI  - Nanoscale spin rectifiers controlled by the Stark effect.
AB  - The control of orbitals and spin states of single electrons is a key ingredient
      for quantum information processing and novel detection schemes and is, more
      generally, of great relevance for spintronics. Coulomb and spin blockade in
      double quantum dots enable advanced single-spin operations that would be
      available even for room-temperature applications with sufficiently small devices.
      To date, however, spin operations in double quantum dots have typically been
      observed at sub-kelvin temperatures, a key reason being that it is very
      challenging to scale a double quantum dot system while retaining independent
      field-effect control of individual dots. Here, we show that the quantum-confined
      Stark effect allows two dots only 5 nm apart to be independently addressed
      without the requirement for aligned nanometre-sized local gating. We thus
      demonstrate a scalable method to fully control a double quantum dot device,
      regardless of its physical size. In the present implementation we present
      InAs/InP nanowire double quantum dots that display an experimentally detectable
      spin blockade up to 10 K. We also report and discuss an unexpected re-entrant
      spin blockade lifting as a function of the magnetic field intensity. 

PMID- 25383515
TI  - An all-in-one nanopore battery array.
AB  - A single nanopore structure that embeds all components of an electrochemical
      storage device could bring about the ultimate miniaturization in energy storage.
      Self-alignment of electrodes within each nanopore may enable closer and more
      controlled spacing between electrodes than in state-of-art batteries. Such an
      'all-in-one' nanopore battery array would also present an alternative to
      interdigitated electrode structures that employ complex three-dimensional
      geometries with greater spatial heterogeneity. Here, we report a battery composed
      of an array of nanobatteries connected in parallel, each composed of an anode, a
      cathode and a liquid electrolyte confined within the nanopores of anodic
      aluminium oxide, as an all-in-one nanosize device. Each nanoelectrode includes an
      outer Ru nanotube current collector and an inner nanotube of V2O5 storage
      material, forming a symmetric full nanopore storage cell with anode and cathode
      separated by an electrolyte region. The V2O5 is prelithiated at one end to serve
      as the anode, with pristine V2O5 at the other end serving as the cathode, forming
      a battery that is asymmetrically cycled between 0.2 V and 1.8 V. The capacity
      retention of this full cell (relative to 1 C values) is 95% at 5 C and 46% at 150
      C, with a 1,000-cycle life. From a fundamental point of view, our all-in-one
      nanopore battery array unveils an electrochemical regime in which ion insertion
      and surface charge mechanisms for energy storage become indistinguishable, and
      offers a testbed for studying ion transport limits in dense nanostructured
      electrode arrays.

PMID- 25383516
TI  - Overcoming the limitations of directed C-H functionalizations of heterocycles.
AB  - In directed C-H activation reactions, any nitrogen or sulphur atoms present in
      heterocyclic substrates will coordinate strongly with metal catalysts. This
      coordination, which can lead to catalyst poisoning or C-H functionalization at an
      undesired position, limits the application of C-H activation reactions in
      heterocycle-based drug discovery, in which regard they have attracted much
      interest from pharmaceutical companies. Here we report a robust and synthetically
      useful method that overcomes the complications associated with performing C-H
      functionalization reactions on heterocycles. Our approach employs a simple N
      methoxy amide group, which serves as both a directing group and an anionic ligand
      that promotes the in situ generation of the reactive PdX2 (X = ArCONOMe) species
      from a Pd(0) source using air as the sole oxidant. In this way, the PdX2 species
      is localized near the target C-H bond, avoiding interference from any nitrogen or
      sulphur atoms present in the heterocyclic substrates. This reaction overrides the
      conventional positional selectivity patterns observed with substrates containing
      strongly coordinating heteroatoms, including nitrogen, sulphur and phosphorus.
      Thus, this operationally simple aerobic reaction demonstrates that it is possible
      to bypass a fundamental limitation that has long plagued applications of directed
      C-H activation in medicinal chemistry. 

PMID- 25383517
TI  - Ischaemic accumulation of succinate controls reperfusion injury through
      mitochondrial ROS.
AB  - Ischaemia-reperfusion injury occurs when the blood supply to an organ is
      disrupted and then restored, and underlies many disorders, notably heart attack
      and stroke. While reperfusion of ischaemic tissue is essential for survival, it
      also initiates oxidative damage, cell death and aberrant immune responses through
      the generation of mitochondrial reactive oxygen species (ROS). Although
      mitochondrial ROS production in ischaemia reperfusion is established, it has
      generally been considered a nonspecific response to reperfusion. Here we develop
      a comparative in vivo metabolomic analysis, and unexpectedly identify widely
      conserved metabolic pathways responsible for mitochondrial ROS production during
      ischaemia reperfusion. We show that selective accumulation of the citric acid
      cycle intermediate succinate is a universal metabolic signature of ischaemia in a
      range of tissues and is responsible for mitochondrial ROS production during
      reperfusion. Ischaemic succinate accumulation arises from reversal of succinate
      dehydrogenase, which in turn is driven by fumarate overflow from purine
      nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After
      reperfusion, the accumulated succinate is rapidly re-oxidized by succinate
      dehydrogenase, driving extensive ROS generation by reverse electron transport at
      mitochondrial complex I. Decreasing ischaemic succinate accumulation by
      pharmacological inhibition is sufficient to ameliorate in vivo ischaemia
      reperfusion injury in murine models of heart attack and stroke. Thus, we have
      identified a conserved metabolic response of tissues to ischaemia and reperfusion
      that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury.
      Furthermore, these findings reveal a new pathway for metabolic control of ROS
      production in vivo, while demonstrating that inhibition of ischaemic succinate
      accumulation and its oxidation after subsequent reperfusion is a potential
      therapeutic target to decrease ischaemia-reperfusion injury in a range of
      pathologies. 

PMID- 25383518
TI  - beta-catenin mediates stress resilience through Dicer1/microRNA regulation.
AB  - beta-catenin is a multi-functional protein that has an important role in the
      mature central nervous system; its dysfunction has been implicated in several
      neuropsychiatric disorders, including depression. Here we show that in mice beta
      catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a
      key brain reward region, an effect mediated by D2-type medium spiny neurons.
      Using genome-wide beta-catenin enrichment mapping, we identify Dicer1-important
      in small RNA (for example, microRNA) biogenesis--as a beta-catenin target gene
      that mediates resilience. Small RNA profiling after excising beta-catenin from
      nucleus accumbens in the context of chronic stress reveals beta-catenin-dependent
      microRNA regulation associated with resilience. Together, these findings
      establish beta-catenin as a critical regulator in the development of behavioural
      resilience, activating a network that includes Dicer1 and downstream microRNAs.
      We thus present a foundation for the development of novel therapeutic targets to
      promote stress resilience.

PMID- 25383519
TI  - The participation of cortical amygdala in innate, odour-driven behaviour.
AB  - Innate behaviours are observed in naive animals without prior learning or
      experience, suggesting that the neural circuits that mediate these behaviours are
      genetically determined and stereotyped. The neural circuits that convey olfactory
      information from the sense organ to the cortical and subcortical olfactory
      centres have been anatomically defined, but the specific pathways responsible for
      innate responses to volatile odours have not been identified. Here we devise
      genetic strategies that demonstrate that a stereotyped neural circuit that
      transmits information from the olfactory bulb to cortical amygdala is necessary
      for innate aversive and appetitive behaviours. Moreover, we use the promoter of
      the activity-dependent gene arc to express the photosensitive ion channel,
      channelrhodopsin, in neurons of the cortical amygdala activated by odours that
      elicit innate behaviours. Optical activation of these neurons leads to
      appropriate behaviours that recapitulate the responses to innate odours. These
      data indicate that the cortical amygdala plays a critical role in generating
      innate odour-driven behaviours but do not preclude its participation in learned
      olfactory behaviours. 

PMID- 25383521
TI  - The neural representation of taste quality at the periphery.
AB  - The mammalian taste system is responsible for sensing and responding to the five
      basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we
      showed that each taste is detected by dedicated taste receptor cells (TRCs) on
      the tongue and palate epithelium. To understand how TRCs transmit information to
      higher neural centres, we examined the tuning properties of large ensembles of
      neurons in the first neural station of the gustatory system. Here, we generated
      and characterized a collection of transgenic mice expressing a genetically
      encoded calcium indicator in central and peripheral neurons, and used a gradient
      refractive index microendoscope combined with high-resolution two-photon
      microscopy to image taste responses from ganglion neurons buried deep at the base
      of the brain. Our results reveal fine selectivity in the taste preference of
      ganglion neurons; demonstrate a strong match between TRCs in the tongue and the
      principal neural afferents relaying taste information to the brain; and expose
      the highly specific transfer of taste information between taste cells and the
      central nervous system. 

PMID- 25383520
TI  - mTORC1-mediated translational elongation limits intestinal tumour initiation and
      growth.
AB  - Inactivation of APC is a strongly predisposing event in the development of
      colorectal cancer, prompting the search for vulnerabilities specific to cells
      that have lost APC function. Signalling through the mTOR pathway is known to be
      required for epithelial cell proliferation and tumour growth, and the current
      paradigm suggests that a critical function of mTOR activity is to upregulate
      translational initiation through phosphorylation of 4EBP1 (refs 6, 7). This model
      predicts that the mTOR inhibitor rapamycin, which does not efficiently inhibit
      4EBP1 (ref. 8), would be ineffective in limiting cancer progression in APC
      deficient lesions. Here we show in mice that mTOR complex 1 (mTORC1) activity is
      absolutely required for the proliferation of Apc-deficient (but not wild-type)
      enterocytes, revealing an unexpected opportunity for therapeutic intervention.
      Although APC-deficient cells show the expected increases in protein synthesis,
      our study reveals that it is translation elongation, and not initiation, which is
      the rate-limiting component. Mechanistically, mTORC1-mediated inhibition of eEF2
      kinase is required for the proliferation of APC-deficient cells. Importantly,
      treatment of established APC-deficient adenomas with rapamycin (which can target
      eEF2 through the mTORC1-S6K-eEF2K axis) causes tumour cells to undergo growth
      arrest and differentiation. Taken together, our data suggest that inhibition of
      translation elongation using existing, clinically approved drugs, such as the
      rapalogs, would provide clear therapeutic benefit for patients at high risk of
      developing colorectal cancer.

PMID- 25383522
TI  - Approaching disorder-free transport in high-mobility conjugated polymers.
AB  - Conjugated polymers enable the production of flexible semiconductor devices that
      can be processed from solution at low temperatures. Over the past 25 years,
      device performance has improved greatly as a wide variety of molecular structures
      have been studied. However, one major limitation has not been overcome; transport
      properties in polymer films are still limited by pervasive conformational and
      energetic disorder. This not only limits the rational design of materials with
      higher performance, but also prevents the study of physical phenomena associated
      with an extended pi-electron delocalization along the polymer backbone. Here we
      report a comparative transport study of several high-mobility conjugated polymers
      by field-effect-modulated Seebeck, transistor and sub-bandgap optical absorption
      measurements. We show that in several of these polymers, most notably in a
      recently reported, indacenodithiophene-based donor-acceptor copolymer with a near
      amorphous microstructure, the charge transport properties approach intrinsic
      disorder-free limits at which all molecular sites are thermally accessible.
      Molecular dynamics simulations identify the origin of this long sought-after
      regime as a planar, torsion-free backbone conformation that is surprisingly
      resilient to side-chain disorder. Our results provide molecular-design guidelines
      for 'disorder-free' conjugated polymers. 

PMID- 25383523
TI  - Transcriptional regulation of autophagy by an FXR-CREB axis.
AB  - Lysosomal degradation of cytoplasmic components by autophagy is essential for
      cellular survival and homeostasis under nutrient-deprived conditions. Acute
      regulation of autophagy by nutrient-sensing kinases is well defined, but longer
      term transcriptional regulation is relatively unknown. Here we show that the fed
      state sensing nuclear receptor farnesoid X receptor (FXR) and the fasting
      transcriptional activator cAMP response element-binding protein (CREB)
      coordinately regulate the hepatic autophagy gene network. Pharmacological
      activation of FXR repressed many autophagy genes and inhibited autophagy even in
      fasted mice, and feeding-mediated inhibition of macroautophagy was attenuated in
      FXR-knockout mice. From mouse liver chromatin immunoprecipitation and high
      throughput sequencing data, FXR and CREB binding peaks were detected at 178 and
      112 genes, respectively, out of 230 autophagy-related genes, and 78 genes showed
      shared binding, mostly in their promoter regions. CREB promoted autophagic
      degradation of lipids, or lipophagy, under nutrient-deprived conditions, and FXR
      inhibited this response. Mechanistically, CREB upregulated autophagy genes,
      including Atg7, Ulk1 and Tfeb, by recruiting the coactivator CRTC2. After feeding
      or pharmacological activation, FXR trans-repressed these genes by disrupting the
      functional CREB-CRTC2 complex. This study identifies the new FXR-CREB axis as a
      key physiological switch regulating autophagy, resulting in sustained nutrient
      regulation of autophagy during feeding/fasting cycles. 

PMID- 25383524
TI  - Metallization of vanadium dioxide driven by large phonon entropy.
AB  - Phase competition underlies many remarkable and technologically important
      phenomena in transition metal oxides. Vanadium dioxide (VO2) exhibits a first
      order metal-insulator transition (MIT) near room temperature, where conductivity
      is suppressed and the lattice changes from tetragonal to monoclinic on cooling.
      Ongoing attempts to explain this coupled structural and electronic transition
      begin with two alternative starting points: a Peierls MIT driven by instabilities
      in electron-lattice dynamics and a Mott MIT where strong electron-electron
      correlations drive charge localization. A key missing piece of the VO2 puzzle is
      the role of lattice vibrations. Moreover, a comprehensive thermodynamic treatment
      must integrate both entropic and energetic aspects of the transition. Here we
      report that the entropy driving the MIT in VO2 is dominated by strongly
      anharmonic phonons rather than electronic contributions, and provide a direct
      determination of phonon dispersions. Our ab initio calculations identify softer
      bonding in the tetragonal phase, relative to the monoclinic phase, as the origin
      of the large vibrational entropy stabilizing the metallic rutile phase. They
      further reveal how a balance between higher entropy in the metal and orbital
      driven lower energy in the insulator fully describes the thermodynamic forces
      controlling the MIT. Our study illustrates the critical role of anharmonic
      lattice dynamics in metal oxide phase competition, and provides guidance for the
      predictive design of new materials. 

PMID- 25383526
TI  - Biochemistry: succinate strikes.

PMID- 25383525
TI  - Structure and function of a single-chain, multi-domain long-chain acyl-CoA
      carboxylase.
AB  - Biotin-dependent carboxylases are widely distributed in nature and have important
      functions in the metabolism of fatty acids, amino acids, carbohydrates,
      cholesterol and other compounds. Defective mutations in several of these enzymes
      have been linked to serious metabolic diseases in humans, and acetyl-CoA
      carboxylase is a target for drug discovery in the treatment of diabetes, cancer
      and other diseases. Here we report the identification and biochemical, structural
      and functional characterizations of a novel single-chain (120 kDa), multi-domain
      biotin-dependent carboxylase in bacteria. It has preference for long-chain acyl
      CoA substrates, although it is also active towards short-chain and medium-chain
      acyl-CoAs, and we have named it long-chain acyl-CoA carboxylase. The holoenzyme
      is a homo-hexamer with molecular mass of 720 kDa. The 3.0 A crystal structure of
      the long-chain acyl-CoA carboxylase holoenzyme from Mycobacterium avium
      subspecies paratuberculosis revealed an architecture that is strikingly different
      from those of related biotin-dependent carboxylases. In addition, the domains of
      each monomer have no direct contact with each other. They are instead extensively
      swapped in the holoenzyme, such that one cycle of catalysis involves the
      participation of four monomers. Functional studies in Pseudomonas aeruginosa
      suggest that the enzyme is involved in the utilization of selected carbon and
      nitrogen sources. 

PMID- 25383527
TI  - A relative shift in cloacal location repositions external genitalia in amniote
      evolution.
AB  - The move of vertebrates to a terrestrial lifestyle required major adaptations in
      their locomotory apparatus and reproductive organs. While the fin-to-limb
      transition has received considerable attention, little is known about the
      developmental and evolutionary origins of external genitalia. Similarities in
      gene expression have been interpreted as a potential evolutionary link between
      the limb and genitals; however, no underlying developmental mechanism has been
      identified. We re-examined this question using micro-computed tomography, lineage
      tracing in three amniote clades, and RNA-sequencing-based transcriptional
      profiling. Here we show that the developmental origin of external genitalia has
      shifted through evolution, and in some taxa limbs and genitals share a common
      primordium. In squamates, the genitalia develop directly from the budding
      hindlimbs, or the remnants thereof, whereas in mice the genital tubercle
      originates from the ventral and tail bud mesenchyme. The recruitment of different
      cell populations for genital outgrowth follows a change in the relative position
      of the cloaca, the genitalia organizing centre. Ectopic grafting of the cloaca
      demonstrates the conserved ability of different mesenchymal cells to respond to
      these genitalia-inducing signals. Our results support a limb-like developmental
      origin of external genitalia as the ancestral condition. Moreover, they suggest
      that a change in the relative position of the cloacal signalling centre during
      evolution has led to an altered developmental route for external genitalia in
      mammals, while preserving parts of the ancestral limb molecular circuitry owing
      to a common evolutionary origin.

PMID- 25383529
TI  - Cell metabolism: autophagy transcribed.

PMID- 25383528
TI  - First cranial remains of a gondwanatherian mammal reveal remarkable mosaicism.
AB  - Previously known only from isolated teeth and lower jaw fragments recovered from
      the Cretaceous and Palaeogene of the Southern Hemisphere, the Gondwanatheria
      constitute the most poorly known of all major mammaliaform radiations. Here we
      report the discovery of the first skull material of a gondwanatherian, a complete
      and well-preserved cranium from Upper Cretaceous strata in Madagascar that we
      assign to a new genus and species. Phylogenetic analysis strongly supports its
      placement within Gondwanatheria, which are recognized as monophyletic and closely
      related to multituberculates, an evolutionarily successful clade of Mesozoic
      mammals known almost exclusively from the Northern Hemisphere. The new taxon is
      the largest known mammaliaform from the Mesozoic of Gondwana. Its craniofacial
      anatomy reveals that it was herbivorous, large-eyed and agile, with well
      developed high-frequency hearing and a keen sense of smell. The cranium exhibits
      a mosaic of primitive and derived features, the disparity of which is extreme and
      probably reflective of a long evolutionary history in geographic isolation. 

PMID- 25383530
TI  - Structural insight into autoinhibition and histone H3-induced activation of
      DNMT3A.
AB  - DNA methylation is an important epigenetic modification that is essential for
      various developmental processes through regulating gene expression, genomic
      imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is
      established during embryogenesis by de novo DNA methyltransferases, DNMT3A and
      DNMT3B, and the methylation patterns vary with developmental stages and cell
      types. DNA methyltransferase 3-like protein (DNMT3L) is a catalytically inactive
      paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a.
      Recent studies have established a connection between DNA methylation and histone
      modifications, and revealed a histone-guided mechanism for the establishment of
      DNA methylation. The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes
      unmethylated histone H3 (H3K4me0). The histone H3 tail stimulates the enzymatic
      activity of Dnmt3a in vitro, whereas the molecular mechanism remains elusive.
      Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3
      tail stimulates its activity in a DNMT3L-independent manner. We determine the
      crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3
      (active form) complexes at 3.82 and 2.90 A resolution, respectively. Structural
      and biochemical analyses indicate that the ADD domain of DNMT3A interacts with
      and inhibits enzymatic activity of the catalytic domain (CD) through blocking its
      DNA-binding affinity. Histone H3 (but not H3K4me3) disrupts ADD-CD interaction,
      induces a large movement of the ADD domain, and thus releases the autoinhibition
      of DNMT3A. The finding adds another layer of regulation of DNA methylation to
      ensure that the enzyme is mainly activated at proper targeting loci when
      unmethylated H3K4 is present, and strongly supports a negative correlation
      between H3K4me3 and DNA methylation across the mammalian genome. Our study
      provides a new insight into an unexpected autoinhibition and histone H3-induced
      activation of the de novo DNA methyltransferase after its initial genomic
      positioning. 

PMID- 25383531
TI  - X-ray structure of a calcium-activated TMEM16 lipid scramblase.
AB  - The TMEM16 family of proteins, also known as anoctamins, features a remarkable
      functional diversity. This family contains the long sought-after Ca(2+)-activated
      chloride channels as well as lipid scramblases and cation channels. Here we
      present the crystal structure of a TMEM16 family member from the fungus Nectria
      haematococca that operates as a Ca(2+)-activated lipid scramblase. Each subunit
      of the homodimeric protein contains ten transmembrane helices and a hydrophilic
      membrane-traversing cavity that is exposed to the lipid bilayer as a potential
      site of catalysis. This cavity harbours a conserved Ca(2+)-binding site located
      within the hydrophobic core of the membrane. Mutations of residues involved in
      Ca(2+) coordination affect both lipid scrambling in N. haematococca TMEM16 and
      ion conduction in the Cl(-) channel TMEM16A. The structure reveals the general
      architecture of the family and its mode of Ca(2+) activation. It also provides
      insight into potential scrambling mechanisms and serves as a framework to unravel
      the conduction of ions in certain TMEM16 proteins.

PMID- 25383532
TI  - Neurobiology: a molecular knife to dice depression.

PMID- 25383533
TI  - Global diets link environmental sustainability and human health.
AB  - Diets link environmental and human health. Rising incomes and urbanization are
      driving a global dietary transition in which traditional diets are replaced by
      diets higher in refined sugars, refined fats, oils and meats. By 2050 these
      dietary trends, if unchecked, would be a major contributor to an estimated 80 per
      cent increase in global agricultural greenhouse gas emissions from food
      production and to global land clearing. Moreover, these dietary shifts are
      greatly increasing the incidence of type II diabetes, coronary heart disease and
      other chronic non-communicable diseases that lower global life expectancies.
      Alternative diets that offer substantial health benefits could, if widely
      adopted, reduce global agricultural greenhouse gas emissions, reduce land
      clearing and resultant species extinctions, and help prevent such diet-related
      chronic non-communicable diseases. The implementation of dietary solutions to the
      tightly linked diet-environment-health trilemma is a global challenge, and
      opportunity, of great environmental and public health importance. 

PMID- 25383534
TI  - Structural biology: Calcium-activated proteins visualized.

PMID- 25383535
TI  - Diet: Food choices for health and planet.

PMID- 25383536
TI  - A basal ichthyosauriform with a short snout from the Lower Triassic of China.
AB  - The incompleteness of the fossil record obscures the origin of many of the more
      derived clades of vertebrates. One such group is the Ichthyopterygia, a clade of
      obligatory marine reptiles that appeared in the Early Triassic epoch, without any
      known intermediates. Here we describe a basal ichthyosauriform from the upper
      Lower Triassic (about 248 million years ago) of China, whose primitive skeleton
      indicates possible amphibious habits. It is smaller than ichthyopterygians and
      had unusually large flippers that probably allowed limited terrestrial
      locomotion. It also retained characteristics of terrestrial diapsid reptiles,
      including a short snout and body trunk. Unlike more-derived ichthyosauriforms, it
      was probably a suction feeder. The new species supports the sister-group
      relationships between ichthyosauriforms and Hupehsuchia, the two forming the
      Ichthyosauromorpha. Basal ichthyosauromorphs are known exclusively from south
      China, suggesting that the clade originated in the region, which formed a warm
      and humid tropical archipelago in the Early Triassic. The oldest unequivocal
      record of a sauropterygian is also from the same stratigraphic unit of the
      region.

PMID- 25383538
TI  - Mammalian evolution: A beast of the southern wild.

PMID- 25383537
TI  - Resolving the complexity of the human genome using single-molecule sequencing.
AB  - The human genome is arguably the most complete mammalian reference assembly, yet
      more than 160 euchromatic gaps remain and aspects of its structural variation
      remain poorly understood ten years after its completion. To identify missing
      sequence and genetic variation, here we sequence and analyse a haploid human
      genome (CHM1) using single-molecule, real-time DNA sequencing. We close or extend
      55% of the remaining interstitial gaps in the human GRCh37 reference genome--78%
      of which carried long runs of degenerate short tandem repeats, often several
      kilobases in length, embedded within (G+C)-rich genomic regions. We resolve the
      complete sequence of 26,079 euchromatic structural variants at the base-pair
      level, including inversions, complex insertions and long tracts of tandem
      repeats. Most have not been previously reported, with the greatest increases in
      sensitivity occurring for events less than 5 kilobases in size. Compared to the
      human reference, we find a significant insertional bias (3:1) in regions
      corresponding to complex insertions and long short tandem repeats. Our results
      suggest a greater complexity of the human genome in the form of variation of
      longer and more complex repetitive DNA that can now be largely resolved with the
      application of this longer-read sequencing technology.

PMID- 25383539
TI  - Nutrient-sensing nuclear receptors coordinate autophagy.
AB  - Autophagy is an evolutionarily conserved catabolic process that recycles
      nutrients upon starvation and maintains cellular energy homeostasis. Its acute
      regulation by nutrient-sensing signalling pathways is well described, but its
      longer-term transcriptional regulation is not. The nuclear receptors peroxisome
      proliferator-activated receptor-alpha (PPARalpha) and farnesoid X receptor (FXR)
      are activated in the fasted and fed liver, respectively. Here we show that both
      PPARalpha and FXR regulate hepatic autophagy in mice. Pharmacological activation
      of PPARalpha reverses the normal suppression of autophagy in the fed state,
      inducing autophagic lipid degradation, or lipophagy. This response is lost in
      PPARalpha knockout (Ppara(-/-), also known as Nr1c1(-/-)) mice, which are
      partially defective in the induction of autophagy by fasting. Pharmacological
      activation of the bile acid receptor FXR strongly suppresses the induction of
      autophagy in the fasting state, and this response is absent in FXR knockout (Fxr(
      /-), also known as Nr1h4(-/-)) mice, which show a partial defect in suppression
      of hepatic autophagy in the fed state. PPARalpha and FXR compete for binding to
      shared sites in autophagic gene promoters, with opposite transcriptional outputs.
      These results reveal complementary, interlocking mechanisms for regulation of
      autophagy by nutrient status. 

PMID- 25383540
TI  - p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration.
AB  - Lung diseases such as chronic obstructive pulmonary disease and pulmonary
      fibrosis involve the progressive and inexorable destruction of oxygen exchange
      surfaces and airways, and have emerged as a leading cause of death worldwide.
      Mitigating therapies, aside from impractical organ transplantation, remain
      limited and the possibility of regenerative medicine has lacked empirical
      support. However, it is clinically known that patients who survive sudden,
      massive loss of lung tissue from necrotizing pneumonia or acute respiratory
      distress syndrome often recover full pulmonary function within six months.
      Correspondingly, we recently demonstrated lung regeneration in mice following
      H1N1 influenza virus infection, and linked distal airway stem cells expressing
      Trp63 (p63) and keratin 5, called DASC(p63/Krt5), to this process. Here we show
      that pre-existing, intrinsically committed DASC(p63/Krt5) undergo a proliferative
      expansion in response to influenza-induced lung damage, and assemble into nascent
      alveoli at sites of interstitial lung inflammation. We also show that the
      selective ablation of DASC(p63/Krt5) in vivo prevents this regeneration, leading
      to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate
      that single DASC(p63/Krt5)-derived pedigrees differentiate to type I and type II
      pneumocytes as well as bronchiolar secretory cells following transplantation to
      infected lung and also minimize the structural consequences of endogenous stem
      cell loss on this process. The ability to propagate these cells in culture while
      maintaining their intrinsic lineage commitment suggests their potential in stem
      cell-based therapies for acute and chronic lung diseases. 

PMID- 25383541
TI  - The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C.
AB  - The spindle assembly checkpoint (SAC) maintains genomic stability by delaying
      chromosome segregation until the last chromosome has attached to the mitotic
      spindle. The SAC prevents the anaphase promoting complex/cyclosome (APC/C)
      ubiquitin ligase from recognizing cyclin B and securin by catalysing the
      incorporation of the APC/C co-activator, CDC20, into a complex called the mitotic
      checkpoint complex (MCC). The SAC works through unattached kinetochores
      generating a diffusible 'wait anaphase' signal that inhibits the APC/C in the
      cytoplasm, but the nature of this signal remains a key unsolved problem.
      Moreover, the SAC and the APC/C are highly responsive to each other: the APC/C
      quickly targets cyclin B and securin once all the chromosomes attach in
      metaphase, but is rapidly inhibited should kinetochore attachment be perturbed.
      How this is achieved is also unknown. Here, we show that the MCC can inhibit a
      second CDC20 that has already bound and activated the APC/C. We show how the MCC
      inhibits active APC/C and that this is essential for the SAC. Moreover, this
      mechanism can prevent anaphase in the absence of kinetochore signalling. Thus, we
      propose that the diffusible 'wait anaphase' signal could be the MCC itself, and
      explain how reactivating the SAC can rapidly inhibit active APC/C. 

PMID- 25383542
TI  - Continental-scale footprint of balancing and positive selection in a small rodent
      (Microtus arvalis).
AB  - Genetic adaptation to different environmental conditions is expected to lead to
      large differences between populations at selected loci, thus providing a
      signature of positive selection. Whereas balancing selection can maintain
      polymorphisms over long evolutionary periods and even geographic scale, thus
      leads to low levels of divergence between populations at selected loci. However,
      little is known about the relative importance of these two selective forces in
      shaping genomic diversity, partly due to difficulties in recognizing balancing
      selection in species showing low levels of differentiation. Here we address this
      problem by studying genomic diversity in the European common vole (Microtus
      arvalis) presenting high levels of differentiation between populations (average F
      ST = 0.31). We studied 3,839 Amplified Fragment Length Polymorphism (AFLP)
      markers genotyped in 444 individuals from 21 populations distributed across the
      European continent and hence over different environmental conditions. Our
      statistical approach to detect markers under selection is based on a Bayesian
      method specifically developed for AFLP markers, which treats AFLPs as a nearly
      codominant marker system, and therefore has increased power to detect selection.
      The high number of screened populations allowed us to detect the signature of
      balancing selection across a large geographic area. We detected 33 markers
      potentially under balancing selection, hence strong evidence of stabilizing
      selection in 21 populations across Europe. However, our analyses identified four
      times more markers (138) being under positive selection, and geographical
      patterns suggest that some of these markers are probably associated with alpine
      regions, which seem to have environmental conditions that favour adaptation. We
      conclude that despite favourable conditions in this study for the detection of
      balancing selection, this evolutionary force seems to play a relatively minor
      role in shaping the genomic diversity of the common vole, which is more
      influenced by positive selection and neutral processes like drift and demographic
      history.

PMID- 25383544
TI  - All-solid-state lithium organic battery with composite polymer electrolyte and
      pillar[5]quinone cathode.
AB  - The cathode capacity of common lithium ion batteries (LIBs) using inorganic
      electrodes and liquid electrolytes must be further improved. Alternatively, all
      solid-state lithium batteries comprising the electrode of organic compounds can
      offer much higher capacity. Herein, we successfully fabricated an all-solid-state
      lithium battery based on organic pillar[5]quinone (C35H20O10) cathode and
      composite polymer electrolyte (CPE). The poly(methacrylate) (PMA)/poly(ethylene
      glycol) (PEG)-LiClO4-3 wt % SiO2 CPE has an optimum ionic conductivity of 0.26 mS
      cm(-1) at room temperature. Furthermore, pillar[5]quinine cathode in all-solid
      state battery rendered an average operation voltage of ~2.6 V and a high initial
      capacity of 418 mAh g(-1) with a stable cyclability (94.7% capacity retention
      after 50 cycles at 0.2C rate) through the reversible redox reactions of
      enolate/quinonid carbonyl groups, showing favorable prospect for the device
      application with high capacity. 

PMID- 25383543
TI  - Rare detection of occult hepatitis B virus infection in children of mothers with
      positive hepatitis B surface antigen.
AB  - The prevalence of occult Hepatitis B virus (HBV) infection in children was
      considerably varied from 0.1-64% in different reports. In this study we aimed to
      investigate the prevalence of occult HBV infection among the children born to
      mothers with positive hepatitis B surface antigen (HBsAg) in Jiangsu, China.
      Serum samples were collected from 210 children of 207 mothers with positive
      HBsAg. HBV serological markers were detected by ELISA and HBV DNA was detected by
      nested PCR. Homology comparison of HBV sequences recovered from the child and
      mother was used to define the infection. Three children (1.43%) were positive for
      HBsAg, in whom the HBV pre S and S gene sequence in each child was identical to
      that in her mother. Of the 207 HBsAg-negative children, nine displayed HBV DNA
      positive by two nested PCR assays using primers derived from S and C genes.
      However, the sequence alignment showed that the sequences in each child were
      considerably different from those in his/her mother. Therefore, the sequences
      amplified from the children were very likely resultant from the cross
      contaminations. Furthermore, the nine children with 'positive HBV DNA' were all
      negative for anti-HBc, and one had anti-HBs 3.42 mIU/ml and eight others had anti
      HBs from 72 to >1000 mIU/ml, indicating that the nine children were less likely
      infected with HBV. Therefore, none of the 207 HBsAg-negative children of HBV
      infected mothers was found to have occult HBV infection. We conclude that the
      prevalence of occult HBV infection in vaccinated children born to HBsAg positive
      mothers should be extremely low. We recommend that homology comparison of
      sequences recovered from the child and mother be used to define the occult HBV
      infection in children born to HBV infected mothers. 

PMID- 25383545
TI  - [Temporal sequence in observational studies to establish causality].
AB  - The article includes a brief summary on the scope of the notions of causality and
      risk and considers some operational difficulties that arise when dealing with
      problems associated with them. It underscores the vital importance of timing and
      its link with the most commonly used observational research designs that address
      causal relationships. The article describes in detail the need to record the
      order in which the relevant events occur and how to consider this in the
      analysis. A detailed example of errors that are usually incurred in and their
      effect is provided. 

PMID- 25383547
TI  - A bumpy ride on the diagnostic bench of massive parallel sequencing, the case of
      the mitochondrial genome.
AB  - The advent of massive parallel sequencing (MPS) has revolutionized the field of
      human molecular genetics, including the diagnostic study of mitochondrial (mt)
      DNA dysfunction. The analysis of the complete mitochondrial genome using MPS
      platforms is now common and will soon outrun conventional sequencing. However,
      the development of a robust and reliable protocol is rather challenging. A
      previous pilot study for the re-sequencing of human mtDNA revealed an uneven
      coverage, affecting predominantly part of the plus strand. In an attempt to
      address this problem, we undertook a comparative study of standard and modified
      protocols for the Ion Torrent PGM system. We could not improve strand
      representation by altering the recommended shearing methodology of the standard
      workflow or omitting the DNA polymerase amplification step from the library
      construction process. However, we were able to associate coverage bias of the
      plus strand with a specific sequence motif. Additionally, we compared coverage
      and variant calling across technologies. The same samples were also sequenced on
      a MiSeq device which showed that coverage and heteroplasmic variant calling were
      much improved. 

PMID- 25383546
TI  - The synthetic tryptanthrin analogue suppresses STAT3 signaling and induces
      caspase dependent apoptosis via ERK up regulation in human leukemia HL-60 cells.
AB  - Tryptanthrin is a natural product which has been reported to have several
      medicinal properties. In this study, we tried to investigate the detailed
      molecular mechanism of its bromo analogue (TBr), a potent cytotoxic agent in the
      induction of cancer cell death. It was found that TBr primarily targets STAT3 and
      ERK signaling during the induction of apoptosis in several human leukemia cell
      lines. In HL-60 cells, TBr treatment caused early down regulation of p-STAT3 with
      concomitant up regulation of p-ERK which led to the activation of intrinsic and
      extrinsic pathways of apoptosis. The mechanism of TBr mediated inhibition of p
      STAT3 was found to be due to the activation of ubiquitin dependent degradation of
      tyrosine 705 and serine 727 p-STAT3. As IL-6 is the main driver of the STAT3
      pathway, the effect of TBr on cell death was subdued when treated in the
      combination with IL-6 in HL60 cells. Interestingly, PD98059 significantly reduced
      the apoptotic effects of TBr, thus showing the direct involvement of p-ERK in TBr
      mediated cell death. It was further shown that apoptotic protein Bax silencing in
      HL-60 cells resists TBr mediated ERK dependent apoptosis. In summary, for the
      first time we report the mechanism of TBr mediated cell death in human leukemia
      cell lines by targeting STAT3 and ERK pathways. 

PMID- 25383548
TI  - Reduction of tendon adhesions following administration of Adaprev, a hypertonic
      solution of mannose-6-phosphate: mechanism of action studies.
AB  - Repaired tendons may be complicated by progressive fibrosis, causing adhesion
      formation or tendon softening leading to tendon rupture and subsequent reduced
      range of motion. There are few therapies available which improve the gliding of
      damaged tendons in the hand. We investigate the role of Mannose 6-phosphate (M6P)
      in a 600 mM hypertonic solution (Adaprev) on tendon adhesion formation in vivo
      using a mouse model of severed tendon in conjunction with analysis of collagen
      synthesis, cellular proliferation and receptors involved in TGF beta signalling.
      Cytotoxicity was assessed by measuring tissue residency, mechanical strength and
      cell viability of tendons after treatment with Adaprev. To elicit potential modes
      of action, in vitro and ex vivo studies were performed investigating
      phosphorylation of p38, cell migration and proliferation. Adaprev treatment
      significantly (p<0.05) reduced the development of adhesions and improved collagen
      organisation without reducing overall collagen synthesis following tendon injury
      in vivo. The bioavailability of Adaprev saw a 40% reduction at the site of
      administration over 45 minutes and tendon fibroblasts tolerated up to 120 minutes
      of exposure without significant loss of cell viability or tensile strength. These
      favourable effects were independent of CI-MPR and TGF-beta signalling and
      possibly highlight a novel mechanism of action related to cellular stress
      demonstrated by phosphorylation of p38. The effect of treatment reduced tendon
      fibroblast migration and transiently halted tendon fibroblast proliferation in
      vitro and ex vivo. Our studies demonstrate that the primary mode of action for
      Adaprev is potentially via a physical, non-chemical, hyperosmotic effect. 

PMID- 25383549
TI  - Effect of bioglass on growth and biomineralization of SaOS-2 cells in hydrogel
      after 3D cell bioprinting.
AB  - We investigated the effect of bioglass (bioactive glass) on growth and
      mineralization of bone-related SaOS-2 cells, encapsulated into a printable and
      biodegradable alginate/gelatine hydrogel. The hydrogel was supplemented either
      with polyphosphate (polyP), administered as polyP * Ca2+-complex, or silica, or
      as biosilica that had been enzymatically prepared from ortho-silicate by
      silicatein. These hydrogels, together with SaOS-2 cells, were bioprinted to
      computer-designed scaffolds. The results revealed that bioglass (nano)particles,
      with a size of 55 nm and a molar ratio of SiO2 : CaO : P2O5 of 55 : 40 : 5, did
      not affect the growth of the encapsulated cells. If silica, biosilica, or polyP *
      Ca2+-complex is co-added to the cell-containing alginate/gelatin hydrogel the
      growth behavior of the cells is not changed. Addition of 5 mg/ml of bioglass
      particles to this hydrogel significantly enhanced the potency of the entrapped
      SaOS-2 cells to mineralize. If compared with the extent of the cells to form
      mineral deposits in the absence of bioglass, the cells exposed to bioglass
      together with 100 umoles/L polyP * Ca2+-complex increased their mineralization
      activity from 2.1- to 3.9-fold, or with 50 umoles/L silica from 1.8- to 2.9-fold,
      or with 50 umoles/L biosilica from 2.7- to 4.8-fold or with the two components
      together (100 umoles/L polyP * Ca2+-complex and 50 umoles/L biosilica) from 4.1-
      to 6.8-fold. Element analysis by EDX spectrometry of the mineral nodules formed
      by SaOS-2 revealed an accumulation of O, P, Ca and C, indicating that the mineral
      deposits contain, besides Ca-phosphate also Ca-carbonate. The results show that
      bioglass added to alginate/gelatin hydrogel increases the proliferation and
      mineralization of bioprinted SaOS-2 cells. We conclude that the development of
      cell-containing scaffolds consisting of a bioprintable, solid and cell-compatible
      inner matrix surrounded by a printable hard and flexible outer matrix containing
      bioglass, provide a suitable strategy for the fabrication of morphogenetically
      active and biodegradable implants.

PMID- 25383550
TI  - Maintenance of sex-related genes and the co-occurrence of both mating types in
      Verticillium dahliae.
AB  - Verticillium dahliae is a cosmopolitan, soilborne fungus that causes a
      significant wilt disease on a wide variety of plant hosts including economically
      important crops, ornamentals, and timber species. Clonal expansion through
      asexual reproduction plays a vital role in recurring plant epidemics caused by
      this pathogen. The recent discovery of recombination between clonal lineages and
      preliminary investigations of the meiotic gene inventory of V. dahliae suggest
      that cryptic sex appears to be rare in this species. Here we expanded on previous
      findings on the sexual nature of V. dahliae. Only 1% of isolates in a global
      collection of 1120 phytopathogenic V. dahliae isolates contained the MAT1-1
      idiomorph, whereas 99% contained MAT1-2. Nine unique multilocus microsatellite
      types comprised isolates of both mating types, eight of which were collected from
      the same substrate at the same time. Orthologs of 88 previously characterized sex
      related genes from fungal model systems in the Ascoymycota were identified in the
      genome of V. dahliae, out of 93 genes investigated. Results of RT-PCR experiments
      using both mating types revealed that 10 arbitrarily chosen sex-related genes,
      including MAT1-1-1 and MAT1-2-1, were constitutively expressed in V. dahliae
      cultures grown under laboratory conditions. Ratios of non-synonymous (amino-acid
      altering) to synonymous (silent) substitutions in V. dahliae MAT1-1-1 and MAT1-2
      1 sequences were indistinguishable from the ratios observed in the MAT genes of
      sexual fungi in the Pezizomycotina. Patterns consistent with strong purifying
      selection were also observed in 18 other arbitrarily chosen V. dahliae sex
      related genes, relative to the patterns in orthologs from fungi with known sexual
      stages. This study builds upon recent findings from other laboratories and mounts
      further evidence for an ancestral or cryptic sexual stage in V. dahliae. 

PMID- 25383551
TI  - Association between blood cadmium levels and 10-year coronary heart disease risk
      in the general Korean population: the Korean National Health and Nutrition
      Examination Survey 2008-2010.
AB  - BACKGROUND: Non-occupational heavy metals are considered risk factors for
      coronary heart disease (CHD). Several recent epidemiologic studies have evaluated
      the relationship between non-occupational cadmium exposure and risk factors for
      cardiovascular disease (CVD). This study was designed to investigate the
      relationship between non-occupational cadmium exposure and risk factors for CHD
      using the Framingham estimate of 10 year CHD risk. METHODS: The heavy metal
      dataset of the Korean National Health and Nutrition Examination Survey for 2008
      through 2010, a cross-sectional survey of a representative sample of 4,668 non
      institutionalized Koreans, was analyzed. Subjects were stratified into seven age
      groups to minimize the effects of age. The log-transformed blood cadmium
      concentrations were compared with the Framingham estimate of 10 year CHD risk in
      each age stratum. RESULTS: The Framingham estimate of 10 year CHD risk was
      significantly associated with the log-transformed blood cadmium concentrations
      (p<0.05) in all age groups of Korean men, with the lowest regression coefficient
      (0.254) for men aged 20 to <35 years and the highest (3.354) for men aged 55 to
      <60 years; similar results, however, were not observed in Korean women. After
      adjusting for survey year, age, and urinary cotinine concentration, the log
      transformed blood cadmium levels among men aged 20 to <35, 40 to <45, 50 to <55,
      and 60 to <65 years were significantly associated with systolic blood pressure
      (p<0.05), but not with total and high density lipoprotein (HDL) cholesterol
      concentrations. CONCLUSIONS: Cadmium exposure, even at non-occupational levels,
      may be associated with CHD risk in men. Despite the declines in non-occupational
      cadmium exposure over the past several decades, more efforts are needed.

PMID- 25383552
TI  - Large impacts of climatic warming on growth of boreal forests since 1960.
AB  - Boreal forests are sensitive to climatic warming, because low temperatures hold
      back ecosystem processes, such as the mobilization of nitrogen in soils. A
      greening of the boreal landscape has been observed using remote sensing, and the
      seasonal amplitude of CO2 in the northern hemisphere has increased, indicating
      warming effects on ecosystem productivity. However, field observations on
      responses of ecosystem productivity have been lacking on a large sub-biome scale.
      Here we report a significant increase in the annual growth of boreal forests in
      Finland in response to climatic warming, especially since 1990. This finding is
      obtained by linking meteorological records and forest inventory data on an area
      between 60 degrees  and 70 degrees  northern latitude. An additional increase in
      growth has occurred in response to changes in other drivers, such as forest
      management, nitrogen deposition and/or CO2 concentration. A similar warming
      impact can be expected in the entire boreal zone, where warming takes place.
      Given the large size of the boreal biome - more than ten million km2- important
      climate feedbacks are at stake, such as the future carbon balance, transpiration
      and albedo. 

PMID- 25383553
TI  - Primary localization and tumor thickness as prognostic factors of survival in
      patients with mucosal melanoma.
AB  - BACKGROUND: Data on survival with mucosal melanoma and on prognostic factors of
      are scarce. It is still unclear if the disease course allows for mucosal melanoma
      to be treated as primary cutaneous melanoma or if differences in overall survival
      patterns require adapted therapeutic approaches. Furthermore, this investigation
      is the first to present 10-year survival rates for mucosal melanomas of different
      anatomical localizations. METHODOLOGY: 116 cases from Sep 10 1984 until Feb 15
      2011 retrieved from the Comprehensive Cancer Center and of the Central Register
      of the German Dermatologic Society databases in Tubingen were included in our
      analysis. We recorded anatomical location and tumor thickness, and estimated
      overall survival at 2, 5 and 10 years and the mean overall survival time.
      Survival times were analyzed with the Kaplan-Meier method. The log-rank test was
      used to compare survival times by localizations and by T-stages. PRINCIPAL
      FINDINGS: We found a median overall survival time of 80.9 months, with an overall
      2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%.
      The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were
      100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with
      melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non
      vulva mucosal melanomas. CONCLUSION: Survival times differed significantly
      between patients with melanomas of the vulva compared to the rest (p = 0.0006).
      It also depends on T-stage at the time of diagnosis (p < 0.0001).

PMID- 25383554
TI  - Isoprene emissions from downy oak under water limitation during an entire growing
      season: what cost for growth?
AB  - Increases in the production of terpene- and phenolic-like compounds in plant
      species under abiotic stress conditions have been interpreted in physiological
      studies as a supplementary defense system due to their capacity to limit cell
      oxidation. From an ecological perspective however, these increases are only
      expected to confer competitive advantages if they do not imply a significant cost
      for the plant, that is, growth reduction. We investigated shifts of isoprene
      emissions, and to a lesser extent phenolic compound concentration, of Quercus
      pubescens Willd. from early leaf development to leaf senescence under optimal
      watering (control: C), mild and severe water stress (MS, SS). The impact of water
      stress was concomitantly assessed on plant physiological (chlorophyll
      fluorescence, stomatal conductance, net photosynthesis, water potential)
      functional (relative leaf water content, leaf mass per area ratio) and growth
      (aerial and root biomass) traits. Growth changes allowed to estimate the eventual
      costs related to the production of isoprene and phenolics. The total phenolic
      content was not modified under water stress whereas isoprene emissions were
      promoted under MS over the entire growing cycle despite the decline of Pn by 35%.
      Under SS, isoprene emissions remained similar to C all over the study despite the
      decline of Pn by 47% and were thereby clearly uncoupled to Pn leading to an
      overestimation of the isoprene emission factor by 44%. Under SS, maintenance of
      isoprene emissions and phenolic compound concentration resulted in very
      significant costs for the plants as growth rates were very significantly reduced.
      Under MS, increases of isoprene emission and maintenance of phenolic compound
      concentration resulted in moderate growth reduction. Hence, it is likely that
      investment in isoprene emissions confers Q. pubescens an important competitive
      advantage during moderate but not severe periods of water scarcity. Consequences
      of this response for air quality in North Mediterranean areas are also discussed.

PMID- 25383556
TI  - Excessive daytime sleepiness and body composition: a population-based study of
      adults.
AB  - BACKGROUND: Excessive daytime sleepiness (EDS) is often associated with increased
      adiposity, particularly when assessed in the context of samples of sleep
      disordered patients; however, it is unclear if this relationship is sustained
      among non-clinical, population-based cohorts. This study aimed to investigate the
      relationship between EDS and a number of body composition markers among a
      population-based sample of men and women. METHODS: This study assessed 1066 women
      aged 21-94 yr (median = 51 yr, IQR 35-66), and 911 men aged 24-92 yr (median = 60
      yr, IQR 46-73) who participated in the Geelong Osteoporosis Study (GOS) between
      the years 2001 and 2008. Total body fat mass was determined from whole body dual
      energy X-ray absorptiometry scans, and anthropometric parameters (weight, height,
      and waist circumference) were measured. Lifestyle and health information was
      collected via self-report. Sleepiness was assessed using the Epworth Sleepiness
      Scale (ESS). Scores of >= 10 were considered indicative of EDS. RESULTS: Women:
      After adjusting for age, alcohol intake, antidepressant medication use and
      physical activity, EDS was associated with greater waist circumference and body
      mass index (BMI). EDS was also associated with 1.5-1.6-fold increased odds of
      being overweight or obese. Men: After adjusting for age, alcohol use, physical
      activity and smoking status, EDS was associated with greater BMI. These findings
      were not explained by the use of sedative or antidepressant medication. EDS was
      also associated with 1.5-fold increased likelihood of being obese, independent of
      these factors. No differences in lean mass, %body fat, or %lean mass were
      detected between those with and without EDS for men or women. CONCLUSIONS: These
      data suggest that EDS is associated with several anthropometric adiposity
      profiles, independent of associated lifestyle and health factors. Among women,
      symptoms of EDS are pervasive at both overweight and obese BMI classifications;
      suggesting a need for further clinical examination to assess possible temporal
      associations with underlying sleep pathology.

PMID- 25383557
TI  - Angiotensin-converting enzyme inhibitors and amyotrophic lateral sclerosis risk:
      a total population-based case-control study.
AB  - IMPORTANCE: Although several studies have shown that use of angiotensin
      converting enzyme inhibitors (ACEIs) potentially decreased amyotrophic lateral
      sclerosis (ALS) risk in animal models, to our knowledge, there has been no human
      study in the literature discussing this issue. OBJECTIVE: To investigate the
      association between the use of ACEIs and the risk for developing ALS. DESIGN,
      SETTING, AND PARTICIPANTS: This case-control study was conducted using the total
      population of Taiwanese citizens seen in general medical practice; therefore, the
      findings can be applied to the general population. The case group comprised 729
      patients with newly diagnosed ALS and a severely disabling disease certificate
      between January 1, 2002, and December 31, 2008. These cases were compared with
      14,580 sex-, age-, residence-, and insurance premium-matched control individuals.
      EXPOSURES: Use of ACEIs was analyzed using a conditional logistic regression
      model that controlled for other antihypertensives, aspirin, steroids,
      nonsteroidal anti-inflammatory drugs, Charlson Comorbidity Index score, length of
      hospital stay, and number of outpatient visits. The cumulative defined daily dose
      (cDDD), which indicates the exposed duration of drug use, was estimated as the
      sum of dispensed DDD of drug and compared with the risk for ALS. MAIN OUTCOMES
      AND MEASURES: All patients with ALS fulfilled El Escorial criteria in this study.
      Medical claim data past 1 to 5 years of ALS first diagnosis date for patients and
      claim data from their matched control individuals were included in the analysis.
      RESULTS: There was a dose-dependent inverse association between ACEI use and the
      risk for developing ALS. When compared with patients who did not use ACEIs, the
      adjusted odds ratios were 0.83 (95% CI, 0.65-1.07; P = .15) for the group
      prescribed ACEIs lower than 449.5 of the cDDD and 0.43 cDDD (95% CI, 0.26-0.72; P
      = .001) for the group with a cumulative ACEI use of greater than 449.5 cDDD. The
      association was most predominant in men older than 55 years. CONCLUSIONS AND
      RELEVANCE: Use of ACEIs exhibited a dose-dependent inverse association with ALS.
      This study demonstrated a 57% risk reduction in the chance for developing ALS in
      people who used ACEIs greater than 449.5 cDDD in 4 years.

PMID- 25383558
TI  - Multitarget therapy for induction treatment of lupus nephritis: a randomized
      trial.
AB  - BACKGROUND: Treatment of lupus nephritis (LN) remains challenging. OBJECTIVE: To
      assess the efficacy and safety of a multitarget therapy consisting of tacrolimus,
      mycophenolate mofetil, and steroid compared with intravenous cyclophosphamide and
      steroid as induction therapy for LN. DESIGN: 24-week randomized, open-label,
      multicenter study. (ClinicalTrials.gov: NCT00876616). SETTING: 26 renal centers
      in China. PATIENTS: Adults (aged 18 to 65 years) with biopsy-proven LN.
      INTERVENTION: Tacrolimus, 4 mg/d, and mycophenolate mofetil, 1.0 g/d, versus
      intravenous cyclophosphamide with a starting dose of 0.75 (adjusted to 0.5 to
      1.0) g/m2 of body surface area every 4 weeks for 6 months. Both groups received 3
      days of pulse methylprednisolone followed by a tapering course of oral prednisone
      therapy. MEASUREMENTS: The primary end point was complete remission at 24 weeks.
      Secondary end points included overall response (complete and partial remission),
      time to overall response, and adverse events. RESULTS: After 24 weeks of therapy,
      more patients in the multitarget group (45.9%) than in the intravenous
      cyclophosphamide group (25.6%) showed complete remission (difference, 20.3
      percentage points [95% CI, 10.0 to 30.6 percentage points]; P < 0.001). The
      overall response incidence was higher in the multitarget group than in the
      intravenous cyclophosphamide group (83.5% vs. 63.0%; difference, 20.4 percentage
      points [CI, 10.3 to 30.6 percentage points]; P < 0.001), and the median time to
      overall response was shorter in the multitarget group (difference, -4.1 weeks
      [CI, -7.9 to -2.1 weeks]). Incidence of adverse events did not differ between the
      multitarget and intravenous cyclophosphamide groups (50.3% [91 of 181] vs. 52.5%
      [95 of 181]). LIMITATION: The study was limited to 24 weeks of follow-up.
      CONCLUSION: Multitarget therapy provides superior efficacy compared with
      intravenous cyclophosphamide as induction therapy for LN. PRIMARY FUNDING SOURCE:
      National Basic Research Program of China, National Key Technology R&D Program.

PMID- 25383559
TI  - Inter- and Intra-individual Variability in the Pharmacokinetics of Agomelatine
      Tablets in Chinese Healthy Male Subjects.
AB  - Agomelatine is an antidepressant with a unique action mechanism differing from
      conventional antidepressants. The high inter- and intra-individual variability of
      agomelatine was previously reported, but no exact data values about the inter-
      and intra-individual variability in AUC and Cmax were mentioned. The current
      study aimed to determine and evaluate the inter- and intra-individual variability
      in AUC and Cmax of agomelatine tablets in Chinese healthy male subjects,
      providing useful information for designing bioequivalence studies of agomelatine.
      Each of 12 Chinese healthy male subjects received a 25-mg agomelatine tablet on 2
      separate periods, and plasma samples were collected up to 24 h after dose and
      analyzed for agomelatine. Inter- and intra-individual variability in the
      pharmacokinetic parameters (Cmax, AUC0-t and AUC0-infinity) of agomelatine was
      assessed. High variations in the plasma concentrations of agomelatine could be
      observed at each sampling time between the different subjects and in one subject
      on different periods. The inter-individual CVs of Cmax, AUC0-t and AUC0-infinity
      were 102.20%, 131.74% and 130.59%, respectively. The intra-individual CVs of
      Cmax, AUC0-t and AUC0-infinity were 84.34%, 49.61% and 50.83%, respectively. The
      results showed high inter- and intra-individual variability in the
      pharmacokinetics of agomelatine in Chinese healthy male subjects, and the intra
      individual variability at CV>80% should be considered in the design of
      bioequivalence studies. 

PMID- 25383560
TI  - Trends in low-risk cesarean delivery in the United States, 1990-2013.
AB  - OBJECTIVES: This report describes trends in low-risk cesarean delivery rates in
      the United States from 1990 through 2013. Trends in low-risk cesarean delivery by
      state of residence, gestational age, age of mother, and race and Hispanic origin
      of mother are examined. METHODS: Low-risk cesarean delivery is defined as a
      cesarean delivery among term (37 or more completed weeks), singleton, vertex
      (head first) births to women giving birth for the first time. Data for 1990-2012
      are based on 100% of low-risk births to residents of all states and the District
      of Columbia. Data for 2013 are preliminary, and are based on nearly 100% of low
      risk births in the United States. RESULTS: The low-risk cesarean delivery rate
      reached a low of 18.4% in 1997 and then rose steadily to a high of 28.1% in 2009.
      The rate decreased from 2009 through 2013, reaching 26.9%. Declines were
      widespread during this time. Low-risk cesarean delivery rates were down for more
      than one-half of states. Rates declined for all term gestational ages (37 or more
      completed weeks); the largest decline was at 38 weeks, down 9%. Rates for all
      maternal age groups and race and Hispanic origin groups were also down. The
      largest declines were for women under 40 (6%-8%) and for non-Hispanic white women
      (6%); rates for these groups decreased at all term gestational ages.

PMID- 25383561
TI  - Delivery of a clinical genomics service.
AB  - Over the past five years, next generation sequencing has revolutionised the
      discovery of genes responsible for rare inherited diseases previously resistant
      to traditional discovery techniques. This review considers how this new
      technology is being introduced into clinical practice to aid diagnosis and
      improve the clinical management of individuals and families affected by rare
      diseases where access to genetic testing was previously limited. We compare and
      contrast the different approaches that have been adopted including panel based
      tests, exome and genome sequencing. We provide insights from our own clinical
      practice demonstrating the challenges and benefits of this new technology. 

PMID- 25383563
TI  - Amniotic fluid lamellar body count as a novel biochemical marker for timing
      elective caesarean delivery.
AB  - The aim of this study is to evaluate the performance of amniotic fluid lamellar
      body count (LBC) on the timing of elective caesarean delivery (CS) at >= 39
      weeks. After allocating the study group (group I, transient tachypnoea of newborn
      (TTN), n = 14), an age-matched control group (group II, no TTN, n = 79) was
      selected for amniotic fluid LBC analysis. The median amniotic fluid LBC levels in
      group I were significantly lower than in the control group. Furthermore, the
      median values of mean lamellar body volume, median lamellar body distribution
      width and lamellar bodycrit in group I were also significantly lower than in
      group II. The best amniotic fluid LBC value to predict TTN was 40.15 * 10(3)/MUl,
      with 82.3% sensitivity and 64.3% specificity. The favourable sensitivity and
      specificity values to predict the TTN for amniotic fluid LBC may suggest using it
      as an elective caesarean delivery-time scheduling marker. 

PMID- 25383562
TI  - Regulation of Pancreatic Beta Cell Stimulus-Secretion Coupling by microRNAs.
AB  - Increased blood glucose after a meal is countered by the subsequent increased
      release of the hypoglycemic hormone insulin from the pancreatic beta cells. The
      cascade of molecular events encompassing the initial sensing and transport of
      glucose into the beta cell, culminating with the exocytosis of the insulin large
      dense core granules (LDCVs) is termed "stimulus-secretion coupling." Impairment
      in any of the relevant processes leads to insufficient insulin release, which
      contributes to the development of type 2 diabetes (T2D). The fate of the beta
      cell, when exposed to environmental triggers of the disease, is determined by the
      possibility to adapt to the new situation by regulation of gene expression. As
      established factors of post-transcriptional regulation, microRNAs (miRNAs) are
      well-recognized mediators of beta cell plasticity and adaptation. Here, we put
      focus on the importance of comprehending the transcriptional regulation of
      miRNAs, and how miRNAs are implicated in stimulus-secretion coupling,
      specifically those influencing the late stages of insulin secretion. We suggest
      that efficient beta cell adaptation requires an optimal balance between
      transcriptional regulation of miRNAs themselves, and miRNA-dependent gene
      regulation. The increased knowledge of the beta cell transcriptional network
      inclusive of non-coding RNAs such as miRNAs is essential in identifying novel
      targets for the treatment of T2D. 

PMID- 25383564
TI  - Flavorings in electronic cigarettes: an unrecognized respiratory health hazard?

PMID- 25383565
TI  - Examining breast cancer screening barriers among Central American and Mexican
      immigrant women: fatalistic beliefs or structural factors?
AB  - Researchers have examined "cancer fatalism" (the belief that cancer is
      predetermined, beyond individual control, and necessarily fatal) as a major
      barrier to breast cancer screening among Latinas. The authors examine perceptions
      of breast cancer, its causes, and experiences with screening among Salvadoran,
      Guatemalan, Mexican, and Bolivian immigrant women in Washington, DC. Two salient
      themes emerged: (a) perceptions of breast cancer causes and breast cancer
      screening; and (b) structural factors are the real barriers to breast cancer
      screening. Findings demonstrate participants' awareness and motivation to get
      screened and elucidate structural barriers that are obscured by the discourse of
      fatalism and hinder breast cancer screening. 

PMID- 25383566
TI  - Automatic hip cartilage segmentation from 3D MR images using arc-weighted graph
      searching.
AB  - Accurate segmentation of hip joint cartilage from magnetic resonance (MR) images
      offers opportunities for quantitative investigations of pathoanatomical
      conditions such as osteoarthritis. In this paper, we present a fully automatic
      scheme for the segmentation of the individual femoral and acetabular cartilage
      plates in the human hip joint from high-resolution 3D MR images. The developed
      scheme uses an improved optimal multi-object multi-surface graph search framework
      with an arc-weighted graph representation that incorporates prior morphological
      knowledge as a basis for segmentation of the individual femoral and acetabular
      cartilage plates despite weak or incomplete boundary interfaces. This automated
      scheme was validated against manual segmentations from 3D true fast imaging with
      steady-state precession (TrueFISP) MR examinations of the right hip joints in 52
      asymptomatic volunteers. Compared with expert manual segmentations of the
      combined, femoral and acetabular cartilage volumes, the automatic scheme obtained
      mean (+/- standard deviation) Dice's similarity coefficients of 0.81 (+/- 0.03),
      0.79 (+/- 0.03) and 0.72 (+/- 0.05). The corresponding mean absolute volume
      difference errors were 8.44% (+/- 6.36), 9.44% (+/- 7.19) and 9.05% (+/- 8.02).
      The mean absolute differences between manual and automated measures of cartilage
      thickness for femoral and acetabular cartilage plates were 0.13 mm (+/- 0.12) and
      0.11 mm (+/- 0.11), respectively.

PMID- 25383567
TI  - Overexpression of cyclic adenosine monophosphate effluent protein MRP4 induces an
      altered response to beta-adrenergic stimulation in the senescent rat heart.
AB  - BACKGROUND: In the senescent heart, the positive inotropic response to beta
      adrenoceptor stimulation is reduced, partly by dysregulation of beta1- and beta3
      adrenoceptors. The multidrug resistance protein 4 (MRP4) takes part in the
      control of intracellular cyclic adenosine monophosphate concentration by
      controlling its efflux but the role of MRP4 in the beta-adrenergic dysfunction of
      the senescent heart remains unknown. METHODS: The beta-adrenergic responses to
      isoproterenol were investigated in vivo (stress echocardiography) and in vitro
      (isolated cardiomyocyte by Ionoptix with sarcomere shortening and calcium
      transient) in young (3 months old) and senescent (24 months old) rats pretreated
      or not with MK571, a specific MRP4 inhibitor. MRP4 was quantified in left
      ventricular homogenates by Western blotting. Data are mean +/- SD expressed as
      percent of baseline value. RESULTS: The positive inotropic effect of
      isoproterenol was reduced in senescent rats in vivo (left ventricular shortening
      fraction 120 +/- 16% vs. 158 +/- 20%, P < 0.001, n = 16 rats) and in vitro
      (sarcomere shortening 129 +/- 37% vs. 148 +/- 35%, P = 0.004, n = 41 or 43 cells)
      as compared to young rats. MRP4 expression increased 3.6-fold in senescent
      compared to young rat myocardium (P = 0.012, n = 8 rats per group). In senescent
      rats, inhibition of MRP4 by MK571 restored the positive inotropic effect of
      isoproterenol in vivo (143 +/- 11%, n = 8 rats). In vitro in senescent
      cardiomyocytes pretreated with MK571, both sarcomere shortening (161 +/- 45% vs.
      129 +/- 37%, P = 0.007, n = 41 cells per group) and calcium transient amplitude
      (132 +/- 25% vs. 113 +/- 27%, P = 0.007) increased significantly. CONCLUSION:
      MRP4 overexpression contributes to the reduction of the positive inotropic
      response to beta-adrenoceptor stimulation in the senescent heart.

PMID- 25383568
TI  - Role of spinal CXCL1 (GROalpha) in opioid tolerance: a human-to-rodent
      translational study.
AB  - BACKGROUND: The pivotal role of glial activation and up-regulated inflammatory
      mediators in the opioid tolerance has been confirmed in rodents but not yet in
      humans. Here, the authors investigated the intraspinal cytokine and chemokine
      profiles of opioid-tolerant cancer patients; and to determine if up-regulated
      chemokines could modify opioid tolerance in rats. METHODS: Cerebrospinal fluid
      samples from opioid-tolerant cancer patients and opioid-naive subjects were
      compared. The cerebrospinal fluid levels of tumor necrosis factor-alpha, CXCL1,
      CXCL10, CCL2, and CX3CL1 were assayed. The rat tail flick test was utilized to
      assess the effects of intrathecal CXCL1 on morphine-induced acute antinociception
      and analgesic tolerance. RESULTS: CXCL1 level in cerebrospinal fluid was
      significantly up-regulated in the opioid-tolerant group (n = 30, 18.8 pg/ml vs.
      13.2 pg/ml, P = 0.02) and was positively correlated (r = 0.49, P < 0.01) with
      opioid dosage. In rat experiment, after induction of tolerance by morphine
      infusion, the spinal cord CXCL1 messenger RNA was up-regulated to 32.5 +/- 11.9
      fold. Although CXCL1 infusion alone did not affect baseline tail-flick latency,
      the analgesic efficacy of a single intraperitoneal injection of morphine dropped
      significantly on day 1 to day 3 after intrathecal infusion of CXCL1. After
      establishing tolerance by intrathecal continuous infusion of morphine, its
      development was accelerated by coadministration of CXCL1 and attenuated by
      coadministration of CXCL1-neutralizing antibody or CXCR2 antagonist. CONCLUSIONS:
      CXCL1 is up-regulated in both opioid-tolerant patients and rodents. The onset and
      extent of opioid tolerance was affected by antagonizing intrathecal CXCL1/CXCR2
      signaling. Therefore, the CXCL1/CXCR2 signal pathway may be a novel target for
      the treatment of opioid tolerance.

PMID- 25383569
TI  - Anaphylaxis to neuromuscular-blocking drugs: all neuromuscular-blocking drugs are
      not the same.

PMID- 25383570
TI  - Big brain, small world?

PMID- 25383571
TI  - Practice advisory on anesthetic care for magnetic resonance imaging: an updated
      report by the american society of anesthesiologists task force on anesthetic care
      for magnetic resonance imaging.

PMID- 25383572
TI  - Management of porous orbital implants requiring explantation: a clinical and
      histopathological study.

PMID- 25383573
TI  - Reply re: "Management of porous orbital implants requiring explantation: a
      clinical and histopathological study".

PMID- 25383574
TI  - Re: "Calcium hydroxyl-apatite (Radiesse) for the correction of periorbital
      hollows, dark circles, and lower eyelid bags".

PMID- 25383575
TI  - Reply re: "Calcium hydroxyl-apatite (Radiesse) for the correction of periorbital
      hollows, dark circles, and lower eyelid bags".

PMID- 25383576
TI  - Re: "Foam sclerotherapy for periorbital dermoid cysts".

PMID- 25383577
TI  - Reply re: "Foam sclerotherapy for periorbital dermoid cysts".

PMID- 25383578
TI  - Re: "Multidisciplinary management of lacrimal sac/nasolacrimal duct carcinomas".

PMID- 25383579
TI  - Re: "Local steroid injection for management of different types of acute
      idiopathic orbital inflammation: an 8-year study".

PMID- 25383580
TI  - Re: "Vascular malformations of the orbit: classification and the role of imaging
      in diagnosis and treatment strategies".

PMID- 25383581
TI  - Managing hospitalized patients with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is the third leading cause of death
      in the United States and is a common diagnosis in outpatient and inpatient
      settings. COPD exacerbations account for more than 800,000 hospital admissions
      annually and are most commonly caused by viral or bacterial infections. This
      article reviews management of patients with COPD exacerbations, including
      recommended diagnostic evaluations and treatments. 

PMID- 25383584
TI  - A validated measure of no sexual attraction: the Asexuality Identification Scale.
AB  - Human asexuality has been described as a lack of sexual attraction toward anyone
      or anything. One percent of the adult population is thought to be asexual, and
      research suggests that asexuality is best conceptualized as a sexual orientation.
      A serious limitation in past research on asexuality has been the complete lack of
      a validated tool to measure asexuality. Due to limitations in recruiting
      sufficiently powered local samples, most studies have relied on recruiting via
      online web-based asexual communities. This is problematic because it limits the
      sample to individuals who have been recruited through established asexuality
      networks/communities. The present study aimed to develop and validate a self
      report questionnaire to assess asexuality. The questionnaire was intended to
      provide a valid measure independent of whether the individual self-identified as
      asexual and was developed in several stages, including: development and
      administration of open-ended questions (209 participants: 139 asexual and 70
      sexual); administration and analysis of resulting 111 items (917 participants:
      165 asexual and 752 sexual); administration and analysis of 37 retained items
      (1,242 participants: 316 asexual and 926 sexual); and validity analysis of the
      final items. The resulting Asexuality Identification Scale (AIS), a 12-item
      questionnaire, is a brief, valid, and reliable self-report instrument for
      assessing asexuality. It is psychometrically sound, easy to administer, and has
      demonstrated ability to discriminate between sexual and asexual individuals. It
      should prove useful to allow researchers to recruit more representative samples
      of the asexual population, permitting for an increased understanding of
      asexuality.

PMID- 25383585
TI  - Antisocial thinking in adolescents: further psychometric development of the
      Antisocial Beliefs and Attitudes Scale (ABAS).
AB  - Investigating the impact of "off-line" cognitive structures on the broad range of
      antisocial behaviors shown by young people has been hampered by the absence of
      psychometrically robust measures of antisocial cognitions. This study evaluates
      the psychometric properties of the Antisocial Beliefs and Attitudes Scale (ABAS),
      a developmentally sensitive measure of young people's beliefs and attitudes
      toward social standards of acceptable behavior at home and at school. The
      reliability and validity of the ABAS was assessed in a sample of British school
      children (N = 486) aged 9-16 years (M = 12.79, SD = 1.90) and male young
      offenders (N = 84) aged 13-17 years (M = 15.15, SD = 0.27). Participants
      completed the ABAS, together with a self-report measure of antisocial behavior;
      maternal reports of antisocial activity were also collected in the offending
      sample. Confirmatory factor analysis replicated the 2-factor structure of Rule
      Noncompliance and Peer Conflict previously derived from a sample of Canadian
      school children, and these factors showed good test-retest reliability. Rule
      Noncompliance predicted self-reported antisocial behavior for ages 11-16 years,
      while Peer Conflict predicted antisocial behavior for ages 9-16 years.
      Comparisons between young offenders and an age-matched subsample of males from
      the school group showed significant differences. In young offenders, Rule
      Noncompliance and Peer Conflict were significantly predictive of self-reported
      antisocial behavior, while Rule Noncompliance independently predicted mothers'
      ratings of their sons' antisocial behavior. These findings provide support for
      the ABAS as a psychometrically sound measure of antisocial thinking.

PMID- 25383582
TI  - Assessing invariance across sex and race/ethnicity in measures of youth
      psychopathic characteristics.
AB  - The aim of this study was to assess the measurement invariance of 2 commonly used
      measures of youth psychopathic characteristics across sex and racial/ethnic
      groups. Among a community sample of Hispanic and Black adolescents (N = 355;
      50.5% female; mean age = 15.09) and their parents, this study tested the
      configural and metric invariance of the Levenson Self-Report Psychopathy Scale
      (LSRP; Levenson, Fitzpatrick, & Kiehl, 1995) and the parent-report version of the
      Inventory of Callous-Unemotional Traits (Frick, 2004). Preliminary analyses
      indicated that the adolescents in the present study reported similar rates of
      psychopathic characteristics as those reported by other studies of adolescents
      and young adults. Results of the multigroup invariance analyses indicated that
      these measures are invariant across sex and between Hispanic and Black youth. In
      addition, further analyses assessing associations between these measures and a
      number of behavioral and emotional characteristics indicated that scores on the
      LSRP Scale and Callous-Unemotional Traits demonstrate good convergent and
      discriminant validity with few differences by sex or race/ethnicity. To date,
      research on psychopathy has focused predominantly on samples of White males.
      Therefore, it is important that research examines the equivalence of measures of
      psychopathic characteristics across different populations, so that accurate
      assessments can be made to inform intervention and treatment efforts.

PMID- 25383586
TI  - Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF)
      predictors of police officer problem behavior and collateral self-report test
      scores.
AB  - The current study examined the predictive validity of Minnesota Multiphasic
      Personality Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen,
      2008/2011) scores in police officer screenings. We utilized a sample of 712
      police officer candidates (82.6% male) from 2 Midwestern police departments. The
      sample included 426 hired officers, most of whom had supervisor ratings of
      problem behaviors and human resource records of civilian complaints. With the
      full sample, we calculated zero-order correlations between MMPI-2-RF scale scores
      and scale scores from the California Psychological Inventory (Gough, 1956) and
      Inwald Personality Inventory (Inwald, 2006) by gender. In the hired sample, we
      correlated MMPI-2-RF scale scores with the outcome data for males only, owing to
      the relatively small number of hired women. Several scales demonstrated
      meaningful correlations with the criteria, particularly in the thought
      dysfunction and behavioral/externalizing dysfunction domains. After applying a
      correction for range restriction, the correlation coefficient magnitudes were
      generally in the moderate to large range. The practical implications of these
      findings were explored by means of risk ratio analyses, which indicated that
      officers who produced elevations at cutscores lower than the traditionally used
      65 T-score level were as much as 10 times more likely than those scoring below
      the cutoff to exhibit problem behaviors. Overall, the results supported the
      validity of the MMPI-2-RF in this setting. Implications and limitations of this
      study are discussed.

PMID- 25383588
TI  - Staphylococcus aureus infection of the optic nerve.
AB  - A 71-year-old woman presented with painful vision loss in the right eye followed
      by ophthalmoplegia. Magnetic resonance imaging demonstrated optic nerve sheath
      enlargement and enhancement. Biopsy of the optic nerve sheath revealed purulent
      and necrotic material that was positive for methicillin-sensitive Staphylococcus
      aureus. The patient underwent enucleation of the right eye and was treated with
      systemic antibiotics with clinical stabilization. Imaging, pathological and
      treatment aspects of optic nerve sheath abscess are discussed.

PMID- 25383589
TI  - Evidence of multidomain mild cognitive impairment in idiopathic intracranial
      hypertension.
AB  - BACKGROUND: Idiopathic intracranial hypertension (IIH), a disorder of unknown
      etiology, may occur in all age groups, but is most common in young obese women.
      Goals of treatment are to preserve vision and alleviate symptoms, including
      intractable headache, pulsatile tinnitus, and nausea. Cognitive function is not
      addressed routinely during clinical evaluation of IIH patients. The aim of our
      study was to test whether there is cognitive impairment in IIH patients and to
      evaluate the nature and characteristics of cognitive functions. METHODS: Design
      Prospective cross-sectional observational study; Setting-Institutional;Study
      population-Thirty consecutive IIH patients (3 men and 27 women), mean age at time
      of testing was 34.4 years; Procedures-All participants completed a cognitive test
      battery; Outcome measures-Impairment of non-verbal memory, executive function,
      visual spatial processing, attention, motor skills, problem solving, and
      information processing speed in IIH patients. RESULTS: Mean scores for all domain
      index scores were below average for age and education. The global cognitive
      score, attention, and visual spatial indices had the lowest scores. CONCLUSIONS:
      Our results indicate that patients with IIH have mild cognitive impairment. All
      domain measures apart from memory showed a statistically significant difference
      from normal individuals, indicating that there is a form of multidomain cognitive
      impairment in IIH. The relationship between cognitive impairment and chronically
      elevated intracranial pressures and its role in contributing to patient morbidity
      requires further study.

PMID- 25383593
TI  - Physical and sexual violence, childhood sexual abuse and HIV/STI risk behaviour
      among alcohol-using women engaged in sex work in Mongolia.
AB  - Although the prevalence of human immunodeficiency virus (HIV) in Mongolia is low,
      it could increase without strategic prevention strategies. Female sex workers
      (FSWs) often experience barriers to prevention, including interpersonal violence.
      This study investigated if childhood sexual abuse (CSA) or recent physical or
      sexual violence was associated with HIV sexual risk behaviours and if CSA
      modified associations between recent violence and HIV sexual risk behaviours. Two
      hundred twenty-two women who (1) were at least 18 years old and clients at the
      National AIDS Foundation; (2) reported vaginal or anal sex in the past 90 days in
      exchange for money or goods and (3) met criteria for harmful alcohol use in the
      past year were enrolled. In-person interviews assessed sexual risk behaviours and
      violence in childhood and adulthood. Negative binomial regression, ordinary least
      squares regression and modified Poisson regression were performed. Sexual risk
      with paying partners was associated with penetrative CSA and sexual violence by
      paying partners. CSA and recent violence were not associated with sexual risk
      behaviours with intimate partners. CSA modified the association between recent
      sexual violence and unprotected sex with intimate partners. Findings highlight
      the need for integrated violence and sexual risk reduction services to ensure
      safe and effective prevention for FSWs.

PMID- 25383595
TI  - A review of post-concussion syndrome and psychological factors associated with
      concussion.
AB  - OBJECTIVE: This study reviewed several topics related to post-concussion syndrome
      and psychological factors associated with concussion. Topics include
      neurobiological perspectives, psychological predictors of post-concussion
      syndrome including pre-morbid anxiety, anxiety sensitivity and cognitive biases
      and misattribution. In addition, the iatrogenic effects of excessive rest are
      reviewed and treatment options are discussed briefly. MAIN RESULTS: Animal models
      of concussion and mild traumatic brain injury suggest that a concussion can
      result in anxiety and fear reactions. The pathophysiology of depression following
      a concussion appears to be consistent with the cortico-limbic model of
      depression. Additionally, some individuals may be at risk for neurobiological
      depression and/or anxiety following a concussion. The literature also
      demonstrates that pre-morbid and concurrent anxiety increases the risk for
      prolonged concussion recovery. Cognitive biases and misattribution of symptoms
      contribute to lengthy recovery from concussion. In addition, medically prescribed
      excessive cognitive and physical rest may contribute to a protracted concussion
      recovery. Supervised and graduated physical activity, the introduction of anxiety
      reduction techniques and cognitive-behavioural therapy of cognitive biases and
      misattribution are effective means of shortening the length of post-concussion
      syndrome. CONCLUSIONS: Understanding, assessing and treating the psychological
      factors associated with concussion are effective means of preventing or
      shortening the length of post-concussion syndrome.

PMID- 25383596
TI  - Quantification of major compounds from Ixeris dentata, Ixeris dentata Var.
      albiflora, and Ixeris sonchifolia and their comparative anti-inflammatory
      activity in lipopolysaccharide-stimulated RAW 264.7 cells.
AB  - The aim of the present study was to evaluate the comparative anti-inflammatory
      activities of Ixeris dentata (ID), Ixeris dentata var. albiflora (IDA), and
      Ixeris sonchifolia (IS) and to identify the main compounds present in extracts.
      The anti-inflammatory activity was evaluated through lipopolysaccharide (LPS)
      induced nitric oxide (NO) production in RAW 264.7 murine macrophages. Five main
      compounds consisting of chlorogenic acid, caffeic acid, luteolin 7-O-glucoside,
      luteolin 7-O-glucuronide, and luteolin were used for simultaneous high
      performance liquid chromatography quantification. The total phenolic content
      present in ID (30 mg/g GAE), IDA (35.33 mg/g GAE), and IS (43.79 mg/g GAE) was
      correlated to the corresponding LPS-induced NO production inhibitory effect in
      RAW 264.7 cells as expressed with IC(50) values 26.19, 21.43, and 7.59 MUg/mL,
      respectively. Luteolin 7-O-glucoside was found as the major compound in ID (8.76
      mg/g dry weight) and IDA (10.35 mg/g dry weight) and luteolin 7-O-glucuronide was
      the major compound in IS (34.66 mg/g dry weight). Luteolin 7-O-glucoside and
      luteolin 7-O-glucuronide inhibited LPS-induced NO production with IC(50) values
      of 30 and 4.5 MUM, respectively. Furthermore, luteolin, luteolin 7-O-glucoside,
      and luteolin 7-O-glucuronide suppressed the expression of iNOS and COX-2, and t
      BHP-induced ROS generation in LPS-stimulated RAW 264.7 cells. These results
      clearly showed that the anti-inflammatory potential of ID, IDA, and IS extract
      are primarily due to their contents of luteolin 7-O-glucoside and luteolin 7-O
      glucuronide, respectively.

PMID- 25383598
TI  - Placental site trophoblastic tumour 3 years after a complete molar pregnancy with
      atypical localisation.

PMID- 25383597
TI  - Efficient gene transfer and durable transgene expression in grafted rabbit veins.
AB  - Venous bypass grafts are useful treatments for obstructive coronary artery
      disease. However, their usefulness is limited by accelerated atherosclerosis.
      Genetic engineering of venous bypass grafts that prevented atherosclerosis could
      improve long-term graft patency and clinical outcomes. We used a rabbit model of
      jugular vein-to-carotid interposition grafting to develop gene therapy for vein
      graft atherosclerosis. Rabbit veins were easily transduced in situ with a first
      generation adenoviral vector; however, most transgene expression (~80%) was lost
      within 3 days after arterial grafting. This rapid loss of transgene expression
      was not prevented by transducing veins after grafting or by prolonged ex vivo
      transduction. However, delaying vein-graft transduction for 28 days (after the
      vein had adapted to the arterial circulation) prevented this early loss of
      transgene expression. We used the delayed transduction approach to test the
      durability of expression of a therapeutic transgene (apolipoprotein A-I)
      expressed from a helper-dependent adenoviral (HDAd) vector. HDAd DNA and
      apolipoprotein A-I mRNA were easily detectable in transduced vein grafts. Vector
      DNA and mRNA declined by 4 weeks, and then persisted stably for at least 6
      months. Delaying transduction for 28 days after grafting permitted initiation of
      vein-graft neointimal growth and medial thickening before gene transfer. However,
      vein-graft lumen diameter was not compromised, because of gradual outward
      remodeling of grafted veins. Our data highlight the promise of HDAd-mediated gene
      therapy, delivered to arterialized vein grafts, for preventing vein-graft
      atherosclerosis. 

PMID- 25383599
TI  - Combinatorial analysis of developmental cues efficiently converts human
      pluripotent stem cells into multiple neuronal subtypes.
AB  - Specification of cell identity during development depends on exposure of cells to
      sequences of extrinsic cues delivered at precise times and concentrations.
      Identification of combinations of patterning molecules that control cell fate is
      essential for the effective use of human pluripotent stem cells (hPSCs) for basic
      and translational studies. Here we describe a scalable, automated approach to
      systematically test the combinatorial actions of small molecules for the targeted
      differentiation of hPSCs. Applied to the generation of neuronal subtypes, this
      analysis revealed an unappreciated role for canonical Wnt signaling in specifying
      motor neuron diversity from hPSCs and allowed us to define rapid (14 days),
      efficient procedures to generate spinal and cranial motor neurons as well as
      spinal interneurons and sensory neurons. Our systematic approach to improving
      hPSC-targeted differentiation should facilitate disease modeling studies and drug
      screening assays. 

PMID- 25383600
TI  - Fungal pathogenesis: Divide and conquer.

PMID- 25383602
TI  - Manfred Girbardt and Charles Bracker: outstanding pioneers in fungal microscopy.
AB  - Midway through the twentieth century, the availability of new and improved
      optical and electronic microscopes facilitated rapid advances in the elucidation
      of the fine structure of fungal cells. In this Essay, I pay tribute to Manfred
      Girbardt (1919-1991) and Charles Bracker (1938-2012)-two individuals who, despite
      being separated by geography and the restrictions of the Cold War, both made
      equally fundamental discoveries in fungal cell ultrastructure and set high
      standards for specimen manipulation and image processing.

PMID- 25383603
TI  - Recombination: genomic mix 'n' match.

PMID- 25383601
TI  - Enabling the 'host jump': structural determinants of receptor-binding specificity
      in influenza A viruses.
AB  - The recent emergence of the H7N9 avian influenza A virus and its ability to
      infect humans emphasize the epidemic and pandemic potential of these viruses.
      Interspecies transmission is the result of many factors, which ultimately lead to
      a change in the host tropism of the virus. One of the key factors involved is a
      shift in the receptor-binding specificity of the virus, which is mostly
      determined by mutations in the viral haemagglutinin (HA). In this Review, we
      discuss recent crystallographic studies that provide molecular insights into HA
      host receptor interactions that have enabled several influenza A virus subtypes
      to 'jump' from avian to human hosts. 

PMID- 25383605
TI  - Making pyrophosphate visible: the first precipitable and real-time fluorescent
      sensor for pyrophosphate in aqueous solution.
AB  - An in situ generated BINOL-DPA-Zn(ii) complex is presented as a chemo-sensing
      ensemble for the recognition of phosphate-based molecules. The ensemble showed
      high sensitivity and selectivity for pyrophosphates (PPi), and it could be
      successfully applied in imaging PPi in living cells. Notably, the ensemble
      exhibited a very low detection limit (95 nM) for PPi and could realize the real
      time detection of PPi by the naked eye through precipitate experiments. The
      ensemble also showed good selectivity towards ATP, and the selectivity
      coefficient for PPi and ATP was calculated to be 4.1/2.8. 

PMID- 25383606
TI  - Two act as one: unexpected dimers of catechol direct a solid-state [2+2]
      photodimerization in a six-component hydrogen-bonded assembly.
AB  - We describe hydrogen-bonded dimers of catechol that act collectively as a single
      template to direct an intermolecular [2+2] photocycloaddition in the solid state.
      The directed reactivity involves discrete, six-component hydrogen-bonded
      assemblies and a photoreaction that occurs stereoselectively and in quantitative
      yield. 

PMID- 25383604
TI  - Autotrophy at the thermodynamic limit of life: a model for energy conservation in
      acetogenic bacteria.
AB  - Life on earth evolved in the absence of oxygen with inorganic gases as potential
      sources of carbon and energy. Among the alternative mechanisms for carbon dioxide
      (CO2) fixation in the living world, only the reduction of CO2 by the Wood
      Ljungdahl pathway, which is used by acetogenic bacteria, complies with the two
      requirements to sustain life: conservation of energy and production of biomass.
      However, how energy is conserved in acetogenic bacteria has been an enigma since
      their discovery. In this Review, we discuss the latest progress on the
      biochemistry and genetics of the energy metabolism of model acetogens,
      elucidating how these bacteria couple CO2 fixation to energy conservation.

PMID- 25383607
TI  - Summaries for patients. Multitarget therapy for induction treatment of lupus
      nephritis.

PMID- 25383609
TI  - Reasoning the causality of city sprawl, traffic congestion, and green land
      disappearance in Taiwan using the CLD model.
AB  - Many city governments choose to supply more developable land and transportation
      infrastructure with the hope of attracting people and businesses to their cities.
      However, like those in Taiwan, major cities worldwide suffer from traffic
      congestion. This study applies the system thinking logic of the causal loops
      diagram (CLD) model in the System Dynamics (SD) approach to analyze the issue of
      traffic congestion and other issues related to roads and land development in
      Taiwan's cities. Comparing the characteristics of development trends with
      yearbook data for 2002 to 2013 for all of Taiwan's cities, this study explores
      the developing phenomenon of unlimited city sprawl and identifies the cause and
      effect relationships in the characteristics of development trends in traffic
      congestion, high-density population aggregation in cities, land development, and
      green land disappearance resulting from city sprawl. This study provides
      conclusions for Taiwan's cities' sustainability and development (S&D). When
      developing S&D policies, during decision making processes concerning city
      planning and land use management, governments should think with a holistic view
      of carrying capacity with the assistance of system thinking to clarify the
      prejudices in favor of the unlimited developing phenomena resulting from city
      sprawl.

PMID- 25383608
TI  - A community-based comprehensive intervention program for 7200 patients with type
      2 diabetes mellitus in Chongqing (China).
AB  - This study assessed the feasibility of community-based comprehensive intervention
      on Type 2 diabetes mellitus (T2DM) on a large population in China. An
      intervention study was conducted on 7200 T2DM patients within one year and
      consisted of six lectures on health issues, and four times face-to-face lifestyle
      counseling delivered by general health practitioners, at local primary health
      centers (PHCs). A "knowledge, attitude and practice" (KAP) survey and fasting
      plasma glucose (FPG) measurement were conducted at baseline and after the
      intervention, respectively. A total of 6586 T2DM patients completed the
      intervention. After one year intervention, patients' KAP level improved
      significantly (p < 0.001) and the average FPG has decreased from 8.53 mmol/L
      (standard deviation: 2.84) to 7.11 mmol/L (standard deviation: 1.34) (p < 0.001).
      Patients in rural areas and with lower education level showed higher FPG and
      poorer KAP level both before and after the intervention. In conclusion, community
      based comprehensive intervention for T2DM is feasible on a large population.
      Improving and repeating the comprehensive strategy is greatly recommended in
      order to sustain the impact, especially in rural areas and for patients with
      lower education levels.

PMID- 25383610
TI  - Prenatal diagnosis of intestinal volvulus in a foetus with homozygous M470V
      cystic fibrosis gene polymorphism.

PMID- 25383611
TI  - United States life tables, 2010.
AB  - Objectives-This report presents complete period life tables for the United States
      by race, Hispanic origin, and sex, based on agespecific death rates in 2010.
      Methods-Data used to prepare the 2010 life tables are 2010 final mortality
      statistics; April 1, 2010 population estimates based on the 2010 decennial
      census; and 2010 Medicare data for persons aged 66-99. The methodology used to
      estimate the 2010 life tables was first implemented with data year 2008. The
      methodology used to estimate the life tables for the Hispanic population remains
      unchanged from that developed for the publication of life tables by Hispanic
      origin for data year 2006. Results-In 2010, the overall expectation of life at
      birth was 78.7 years. Between 2009 and 2010, life expectancy at birth increased
      for all groups considered. Life expectancy increased for both males (from 76.0 to
      76.2) and females (80.9 to 81.0) and for the white population (78.8 to 78.9), the
      black population (74.7 to 75.1), the Hispanic population (81.1 to 81.4), the non
      Hispanic white population (78.7 to 78.8), and the non-Hispanic black population
      (74.4 to 74.7). 

PMID- 25383612
TI  - Paramecium swimming and ciliary beating patterns: a study on four RNA
      interference mutations.
AB  - Paramecium cells swim and feed by beating their thousands of cilia in coordinated
      patterns. The organization of these patterns and its relationship with cell
      motility has been the subject of a large body of work, particularly as a model
      for ciliary beating in human organs where similar organization is seen. However
      the rapid motion of the cells makes quantitative measurements very challenging.
      Here we provide detailed measurements of the swimming of Paramecium cells from
      high-speed video at high magnification, as they move in microfluidic channels. An
      image analysis protocol allows us to decouple the cell movement from the motion
      of the cilia, thus allowing us to measure the ciliary beat frequency (CBF) and
      the spatio-temporal organization into metachronal waves along the cell periphery.
      Two distinct values of the CBF appear at different regions of the cell: most of
      the cilia beat in the range of 15 to 45 Hz, while the cilia in the peristomal
      region beat at almost double the frequency. The body and peristomal CBF display a
      nearly linear relation with the swimming velocity. Moreover the measurements do
      not display a measurable correlation between the swimming velocity and the
      metachronal wave velocity on the cell periphery. These measurements are repeated
      for four RNAi silenced mutants, where proteins specific to the cilia or to their
      connection to the cell base are depleted. We find that the mutants whose ciliary
      structure is affected display similar swimming to the control cells albeit with a
      reduced efficiency, while the mutations that affect the cilia's anchoring to the
      cell lead to strongly reduced ability to swim. This reduction in motility can be
      related to a loss of coordination between the ciliary beating in different parts
      of the cell. 

PMID- 25383613
TI  - Engineering lead-sensing GFP through rational designing.
AB  - Lead is one of the most hazardous metals ubiquitous in the environment, causing
      serious health hazards to organisms. Recently, fluorescent proteins such as GFP
      and Dsred were utilized for the development of reagent-less rapid metal sensors.
      Here, we demonstrate the development of a lead-sensing GFP that is highly
      sensitive to lead at micro molar concentrations. 

PMID- 25383614
TI  - Introducing a new series - topics and controversies in biostatistics.

PMID- 25383616
TI  - Now is the time for true reform of mental health services.

PMID- 25383615
TI  - Multiscale contribution of bone tissue material property heterogeneity to
      trabecular bone mechanical behavior.
AB  - Heterogeneity of material properties is an important potential contributor to
      bone fracture resistance because of its putative contribution to toughness, but
      establishing the contribution of heterogeneity to fracture risk is still in an
      incipient stage. Experimental studies have demonstrated changes in distributions
      of compositional and nanomechanical properties with fragility fracture history,
      disease, and pharmacologic treatment. Computational studies have demonstrated
      that models with heterogeneous material properties predict apparent stiffness
      moderately better than homogeneous models and show greater energy dissipation.
      Collectively, these results suggest that microscale material heterogeneity
      affects not only microscale mechanics but also structural performance at larger
      length scales.

PMID- 25383617
TI  - Optimal dosage of methylprednisolone for the treatment of sudden hearing loss in
      geriatric patients: a propensity score-matched analysis.
AB  - We aimed to compare the treatment outcomes and the occurrence rates of adverse
      events associated with different steroid regimens in geriatric patients (aged 65
      years or older) with unilateral idiopathic sudden sensorineural hearing loss
      (ISSNHL). After thorough medical chart reviews of 109 patients with ISSNHL
      between May 2006 and December 2013, we performed a propensity score-matched
      analysis using previously known prognostic factors, steroid regimens, and other
      cointerventions. Patients were divided based on their steroid regimens into group
      I (which initially received 48 mg of methylprednisolone daily with a subsequently
      tapered dose) and group II (which initially received 24 mg of methylprednisolone
      daily with a subsequently tapered dose). We compared final hearing and the
      occurrence of adverse events between the two groups. As a result, 20 pairs of
      propensity score-matched patients (n = 40) were enrolled. Group I patients showed
      better final hearing levels compared with group II patients (42.00 +/- 22.35 dB
      and 57.38 +/- 26.40 dB, respectively), although this difference was marginally
      significant (p = 0.058). Based on the comparative analysis of each of the
      frequencies in the final audiograms, lower hearing thresholds at 2 KHz were
      observed in group I (p = 0.049). There was no significant difference in the
      occurrence of adverse effects between the two groups (p>0.05). In conclusion,
      conventional steroid regimens produced adverse event occurrence rates that were
      similar to those of low-dose treatment but may also have produced superior
      hearing recovery. The use of steroid dose reduction in geriatric patients with
      ISSNHL is not preferable to conventional steroid regimens.

PMID- 25383619
TI  - Correlates of depressive symptoms after birth for Latinas who are overweight or
      obese.
AB  - Depression symptoms and overweight/obesity are common concerns during
      childbearing. Both conditions are associated with poor outcomes at birth and can
      have long-lasting consequences. Predictors of depressive symptoms among
      overweight and obese low-income and ethnically diverse women are not known. Data
      are from the Madres para la Salud trial with 139 postpartum Latinas. Depressive
      symptoms during a prior pregnancy were positively related, while social support
      and moderate intensity physical activity (PA) were negatively related to
      depressive symptoms after birth. Social support and PA may be effective
      interventions, particularly for women who have experienced depressive symptoms in
      a prior pregnancy. 

PMID- 25383618
TI  - Phospholipase A2 isolated from the venom of Crotalus durissus terrificus
      inactivates dengue virus and other enveloped viruses by disrupting the viral
      envelope.
AB  - The Flaviviridae family includes several virus pathogens associated with human
      diseases worldwide. Within this family, Dengue virus is the most serious threat
      to public health, especially in tropical and sub-tropical regions of the world.
      Currently, there are no vaccines or specific antiviral drugs against Dengue virus
      or against most of the viruses of this family. Therefore, the development of
      vaccines and the discovery of therapeutic compounds against the medically most
      important flaviviruses remain a global public health priority. We previously
      showed that phospholipase A2 isolated from the venom of Crotalus durissus
      terrificus was able to inhibit Dengue virus and Yellow fever virus infection in
      Vero cells. Here, we present evidence that phospholipase A2 has a direct effect
      on Dengue virus particles, inducing a partial exposure of genomic RNA, which
      strongly suggests inhibition via the cleavage of glycerophospholipids at the
      virus lipid bilayer envelope. This cleavage might induce a disruption of the
      lipid bilayer that causes a destabilization of the E proteins on the virus
      surface, resulting in inactivation. We show by computational analysis that
      phospholipase A2 might gain access to the Dengue virus lipid bilayer through the
      pores found on each of the twenty 3-fold vertices of the E protein shell on the
      virus surface. In addition, phospholipase A2 is able to inactivate other
      enveloped viruses, highlighting its potential as a natural product lead for
      developing broad-spectrum antiviral drugs. 

PMID- 25383620
TI  - Peroxisome proliferator-activated receptor gamma deficiency in T cells
      accelerates chronic rejection by influencing the differentiation of CD4+ T cells
      and alternatively activated macrophages.
AB  - BACKGROUND: In a previous study, activation of the peroxisome proliferator
      activated receptor gamma (PPARgamma) inhibited chronic cardiac rejection.
      However, because of the complexity of chronic rejection and the fact that
      PPARgamma is widely expressed in immune cells, the mechanism of the PPARgamma
      induced protective effect was unclear. MATERIALS AND METHODS: A chronic rejection
      model was established using B6.C-H-2bm12KhEg (H-2bm12) mice as donors, and MHC II
      mismatched T-cell-specific PPARgamma knockout mice or wild type (WT) littermates
      as recipients. The allograft lesion was assessed by histology and
      immunohistochemistry. T cells infiltrates in the allograft were isolated, and
      cytokines and subpopulations were detected using cytokine arrays and flow
      cytometry. Transcription levels in the allograft were measured by RT-PCR. In
      vitro, the T cell subset differentiation was investigated after culture in
      various polarizing conditions. PPARgamma-deficient regulatory T cells (Treg) were
      cocultured with monocytes to test their ability to induce alternatively activated
      macrophages (AAM). RESULTS: T cell-specific PPARgamma knockout recipients
      displayed reduced cardiac allograft survival and an increased degree of pathology
      compared with WT littermates. T cell-specific PPARgamma knockout resulted in more
      CD4+ T cells infiltrating into the allograft and altered the Th1/Th2 and
      Th17/Treg ratios. The polarization of AAM was also reduced by PPARgamma
      deficiency in T cells through the action of Th2 and Treg. PPARgamma-deficient T
      cells eliminated the pioglitazone-induced polarization of AAM and reduced
      allograft survival. CONCLUSIONS: PPARgamma-deficient T cells influenced the T
      cell subset and AAM polarization in chronic allograft rejection. The mechanism of
      PPARgamma activation in transplantation tolerance could yield a novel treatment
      without side effects.

PMID- 25383621
TI  - iTBS-induced LTP-like plasticity parallels oscillatory activity changes in the
      primary sensory and motor areas of macaque monkeys.
AB  - Recently, neuromodulation techniques based on the use of repetitive transcranial
      magnetic stimulation (rTMS) have been proposed as a non-invasive and efficient
      method to induce in vivo long-term potentiation (LTP)-like aftereffects. However,
      the exact impact of rTMS-induced perturbations on the dynamics of neuronal
      population activity is not well understood. Here, in two monkeys, we examine
      changes in the oscillatory activity of the sensorimotor cortex following an
      intermittent theta burst stimulation (iTBS) protocol. We first probed iTBS
      modulatory effects by testing the iTBS-induced facilitation of somatosensory
      evoked potentials (SEP). Then, we examined the frequency information of the
      electrocorticographic signal, obtained using a custom-made miniaturised multi
      electrode array for electrocorticography, after real or sham iTBS. We observed
      that iTBS induced facilitation of SEPs and influenced spectral components of the
      signal, in both animals. The latter effect was more prominent on the theta band
      (4-8 Hz) and the high gamma band (55-90 Hz), de-potentiated and potentiated
      respectively. We additionally found that the multi-electrode array uniformity of
      beta (13-26 Hz) and high gamma bands were also afflicted by iTBS. Our study
      suggests that enhanced cortical excitability promoted by iTBS parallels a dynamic
      reorganisation of the interested neural network. The effect in the gamma band
      suggests a transient local modulation, possibly at the level of synaptic strength
      in interneurons. The effect in the theta band suggests the disruption of temporal
      coordination on larger spatial scales. 

PMID- 25383622
TI  - The efficacy and safety of selective H1-antihistamine versus leukotriene receptor
      antagonist for seasonal allergic rhinitis: a meta-analysis.
AB  - BACKGROUND: Both selective H1-antihistamine (SAH) and leukotriene receptor
      antagonist (LTRA) have been shown to be effective in treating patients with
      seasonal allergic rhinitis (SAR), but it is still uncertain which treatment
      option is optimal. This meta-analysis was aimed to compare the efficacy and
      safety of SAH and LTRA for SAR. MATERIALS AND METHODS: PubMed, EMBASE and the
      Cochrane Library were searched for all eligible studies that compared the
      efficacy and safety of SAH and LTRA for SAR up to September 7, 2014. The pooled
      mean difference (MD), odd ratios (ORs) and 95% confidence intervals (95% CIs)
      were calculated using a fixed- or random-effects model. RESULTS: Nine studies
      with 5781 SAR patients were included. The results showed that SAH is superior to
      LTRA in terms of the daytime eye symptoms score (DESS) and composite symptoms
      score (CSS) for SAR (MD = 0.06, 95% CI, 0.03 to 0.10, P = 0.000, I2 = 99%; MD =
      0.03, 95% CI, 0.01 to 0.05, P = 0.010, I2 = 98%), whereas LTRA overmatched SAH
      with respect to the night-time symptoms score (NSS) (MD = -0.04, 95% CI, -0.05 to
      -0.02, P = 0.000, I2 = 97%). Additionally, the results of subgroup analysis
      indicated that the dose, duration and gender of the patients might impact the
      comparisons of the effects of SAH and LTRA on their efficacy for SAR. CONCLUSION:
      This meta-analysis suggested that SAH and LTRA have similar effects and safety
      for SAR, but SAH is more appropriate for daytime nasal symptoms (congestion,
      rhinorrhea, pruritus and sneezing), while LTRA is better suited for nighttime
      symptoms (difficulty going to sleep, nighttime awakenings, and nasal congestion
      on awakening), respectively. Meanwhile, the dose, duration and gender of patients
      may influence the anti-SAR effects of SAH and LTRA.

PMID- 25383623
TI  - Metagenomic insights into the RDX-degrading potential of the ovine rumen
      microbiome.
AB  - The manufacturing processes of royal demolition explosive (RDX), or hexahydro
      1,3,5-trinitro-1,3,5-triazine, have resulted in serious water contamination. As a
      potential carcinogen, RDX can cause a broad range of harmful effects to humans
      and animals. The ovine rumen is capable of rapid degradation of nitroaromatic
      compounds, including RDX. While ruminal RDX-degrading bacteria have been
      identified, the genes and pathways responsible for RDX degradation in the rumen
      have yet to be characterized. In this study, we characterized the metabolic
      potential of the ovine rumen using metagenomic approaches. Sequences homologous
      to at least five RDX-degrading genes cloned from environmental samples (diaA,
      xenA, xenB, xplA, and xplB) were present in the ovine rumen microbiome. Among
      them, diaA was the most abundant, likely reflective of the predominance of the
      genus Clostridium in the ovine rumen. At least ten genera known to harbor RDX
      degrading microorganisms were detectable. Metagenomic sequences were also
      annotated using public databases, such as Pfam, COG, and KEGG. Five of the six
      Pfam protein families known to be responsible for RDX degradation in
      environmental samples were identified in the ovine rumen. However, increased
      substrate availability did not appear to enhance the proliferation of RDX
      degrading bacteria and alter the microbial composition of the ovine rumen. This
      implies that the RDX-degrading capacity of the ovine rumen microbiome is likely
      regulated at the transcription level. Our results provide metagenomic insights
      into the RDX-degrading potential of the ovine rumen, and they will facilitate the
      development of novel and economic bioremediation strategies. 

PMID- 25383624
TI  - Correlations of differentially expressed gap junction connexins Cx26, Cx30, Cx32,
      Cx43 and Cx46 with breast cancer progression and prognosis.
AB  - BACKGROUND AND AIMS: Connexins and their cell membrane channels contribute to the
      control of cell proliferation and compartmental functions in breast glands and
      their deregulation is linked to breast carcinogenesis. Our aim was to correlate
      connexin expression with tumor progression and prognosis in primary breast
      cancers. MATERIALS AND METHODS: Meta-analysis of connexin isotype expression data
      of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms,
      respectively, was performed. Expressed connexins were also monitored at the
      protein level in tissue microarrays of 127 patients equally representing all
      tumor grades, using immunofluorescence and multilayer, multichannel digital
      microscopy. Prognostic correlations were plotted in Kaplan-Meier curves and
      tested using the log-rank test and cox-regression analysis in univariate and
      multivariate models. RESULTS: The expression of GJA1/Cx43, GJA3/Cx46 and
      GJB2/Cx26 and, for the first time, GJA6/Cx30 and GJB1/Cx32 was revealed both in
      normal human mammary glands and breast carcinomas. Within their subfamilies these
      connexins can form homo- and heterocellular epithelial channels. In cancer, the
      array datasets cross-validated each other's prognostic results. In line with the
      significant correlations found at mRNA level, elevated Cx43 protein levels were
      linked with significantly improved breast cancer outcome, offering Cx43 protein
      detection as an independent prognostic marker stronger than vascular invasion or
      necrosis. As a contrary, elevated Cx30 mRNA and protein levels were associated
      with a reduced disease outcome offering Cx30 protein detection as an independent
      prognostic marker outperforming mitotic index and necrosis. Elevated versus low
      Cx43 protein levels allowed the stratification of grade 2 tumors into good and
      poor relapse free survival subgroups, respectively. Also, elevated versus low
      Cx30 levels stratified grade 3 patients into poor and good overall survival
      subgroups, respectively. CONCLUSION: Differential expression of Cx43 and Cx30 may
      serve as potential positive and negative prognostic markers, respectively, for a
      clinically relevant stratification of breast cancers.

PMID- 25383625
TI  - Removal of pulse artefact from EEG data recorded in MR environment at 3T. Setting
      of ICA parameters for marking artefactual components: application to resting
      state data.
AB  - Simultaneous electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) allow for a non-invasive investigation of cerebral functions with
      high temporal and spatial resolution. The main challenge of such integration is
      the removal of the pulse artefact (PA) that affects EEG signals recorded in the
      magnetic resonance (MR) scanner. Often applied techniques for this purpose are
      Optimal Basis Set (OBS) and Independent Component Analysis (ICA). The combination
      of OBS and ICA is increasingly used, since it can potentially improve the
      correction performed by each technique separately. The present study is focused
      on the OBS-ICA combination and is aimed at providing the optimal ICA parameters
      for PA correction in resting-state EEG data, where the information of interest is
      not specified in latency and amplitude as in, for example, evoked potential. A
      comparison between two intervals for ICA calculation and four methods for marking
      artefactual components was performed. The performance of the methods was
      discussed in terms of their capability to 1) remove the artefact and 2) preserve
      the information of interest. The analysis included 12 subjects and two resting
      state datasets for each of them. The results showed that none of the signal
      lengths for the ICA calculation was highly preferable to the other. Among the
      methods for the identification of PA-related components, the one based on the
      wavelets transform of each component emerged as the best compromise between the
      effectiveness in removing PA and the conservation of the physiological neuronal
      content. 

PMID- 25383626
TI  - Physical inactivity and incidence of obesity among South Australian adults.
AB  - The aim of this paper is to examine the association of physical inactivity with
      incidence of obesity in the South Australian adult population. Two representative
      data sources were used - the South Australian Monitoring and Surveillance System
      (SAMSS), a monthly surveillance system, and the North West Adelaide Health Study
      (NWAHS), a biomedical cohort study. There were 75.3% (n = 12873) SAMSS
      participants and 72.8% (n = 1521) of NWAHS participants that were not obese at
      baseline. The cumulative incidence of obesity for SAMSS participants from the
      previous year to the current year was 2.7%. The cumulative incidence of obesity
      for NWAHS participants between baseline and stage 3 was 14.4%. Physical
      inactivity was associated with incident obesity (RR 1.48, 95% CI 1.14-1.90
      [SAMSS] and RR 1.41, 95% CI 1.03-1.93 [NWAHS]). This association remained, but
      was attenuated after adjustment for chronic conditions, risk factors and socio
      demographic factors. However, physical activity should be continued to be
      encouraged in the population for its known additional health benefits.

PMID- 25383628
TI  - Co-assembled conductive hydrogel of N-fluorenylmethoxycarbonyl phenylalanine with
      polyaniline.
AB  - A metastable coassembled hydrogel of N-Fluorenylmethoxycarbonyl (Fmoc)
      phenylalanine (FP) with aniline (FP-ANI), upon polymerization, produces a stable
      green-colored coassembled FP-polyaniline (FP-PANI) hydrogel. The coassembly is
      produced by supramolecular interactions between FP and ANI/PANI. WAXS spectra
      suggest that structures of FP powder, FP-ANI, and FP-PANI xerogels are different
      from each other. The FP-ANI gel exhibits a mixture of doughnut and fiber
      morphology, but the FP-PANI gel exhibits a nanotubular morphology. UV-vis
      spectroscopy suggests that the doped state of PANI and the fluorescence property
      of FP completely vanish in the FP-PANI gel. The storage and loss modulii (G' and
      G") of the FP-PANI gel are higher than those of the FP-ANI gel. The FP-ANI gel
      breaks at a lower oscillator stress (57 Pa) than the FP-PANI gel (93 Pa), which
      exhibits a good strain recovery demonstrating excellent viscoelastic properties.
      The FP-PANI gel also exhibits a dc conductivity (1.2 * 10(-2) S.cm(-1)) that is
      seven orders higher than that of the FP-ANI gel because of the doped nature of
      PANI. The current-voltage (I-V) characteristic curve of FP-PANI xerogel resembles
      the behavior of a semiconductor-metal junction, and upon white light irradiation,
      it exhibits a reversible on-off cycle with a constant photocurrent value of 0.1
      mA. The Nyquist plot obtained from impedance measurements of the FP-PANI xerogel
      is different from that obtained for the FP-ANI xerogel, and it exhibits almost a
      semicircle, indicating the existence of both resistive and capacitive features
      connected in parallel mode. 

PMID- 25383627
TI  - Discovery of selective and noncovalent diaminopyrimidine-based inhibitors of
      epidermal growth factor receptor containing the T790M resistance mutation.
AB  - Activating mutations within the epidermal growth factor receptor (EGFR) kinase
      domain, commonly L858R or deletions within exon 19, increase EGFR-driven cell
      proliferation and survival and are correlated with impressive responses to the
      EGFR inhibitors erlotinib and gefitinib in nonsmall cell lung cancer patients.
      Approximately 60% of acquired resistance to these agents is driven by a single
      secondary mutation within the EGFR kinase domain, specifically substitution of
      the gatekeeper residue threonine-790 with methionine (T790M). Due to dose
      limiting toxicities associated with inhibition of wild-type EGFR (wtEGFR), we
      sought inhibitors of T790M-containing EGFR mutants with selectivity over wtEGFR.
      We describe the evolution of HTS hits derived from Jak2/Tyk2 inhibitors into
      selective EGFR inhibitors. X-ray crystal structures revealed two distinct binding
      modes and enabled the design of a selective series of novel diaminopyrimidine
      based inhibitors with good potency against T790M-containing mutants of EGFR, high
      selectivity over wtEGFR, broad kinase selectivity, and desirable physicochemical
      properties. 

PMID- 25383629
TI  - Co-exposure of carboxyl-functionalized single-walled carbon nanotubes and 17alpha
      ethinylestradiol in cultured cells: effects on bioactivity and cytotoxicity.
AB  - 17alpha-Ethinylestradiol (EE2) is the representative of environmental estrogens.
      Although EE2 can interact with some engineered nanoparticles (NPs), little is
      known about the bioactivity of NP-associated EE2 in organisms. In this study, we
      investigated the combined effects of the co-exposed carboxyl-functionalized
      single-walled carbon nanotubes (cf-SWCNTs) and EE2 in the human breast
      adenocarcinoma cell line (MCF-7 cells), focusing on the cytotoxicity and
      bioactivity. There were no significant differences in mitochondrial activity,
      membrane damage, and cell apoptosis when exposed to cf-SWCNTs with and without
      adsorbed EE2. However, the bioactivity of adsorbed EE2 on cf-SWCNTs was
      significantly inhibited. The calculated effective concentration of EE2 in
      cultured cells showed that less than 0.2% of the total adsorbed EE2 was released,
      indicating that most EE2 was retained on the cf-SWCNTs during cellular exposure.
      Furthermore, there were no obvious changes in the bioactivity of adsorbed EE2 in
      the culture medium containing 5-20% fetal bovine serum (FBS), even up to 10 days
      of incubation, indicating that the adsorbed EE2 on cf-SWCNTs is highly stable in
      the cell culture medium. These results mark a promising possibility for EE2 to be
      adsorbed by cf-SWCNTs in environmentally relevant settings and thereby influenced
      its toxicity and biological fate. This is also tempting for future studies
      involving risk assessment ways for association between NPs and contaminants in
      the environment. 

PMID- 25383630
TI  - Unraveling hidden order in the dynamics of developed and emerging markets.
AB  - The characterization of asset price returns is an important subject in modern
      finance. Traditionally, the dynamics of stock returns are assumed to lack any
      temporal order. Here we present an analysis of the autocovariance of stock market
      indices and unravel temporal order in several major stock markets. We also
      demonstrate a fundamental difference between developed and emerging markets in
      the past decade - emerging markets are marked by positive order in contrast to
      developed markets whose dynamics are marked by weakly negative order. In
      addition, the reaction to financial crises was found to be reversed among
      developed and emerging markets, presenting large positive/negative autocovariance
      spikes following the onset of these crises. Notably, the Chinese market shows
      neutral or no order while being regarded as an emerging market. These findings
      show that despite the coupling between international markets and global trading,
      major differences exist between different markets, and demonstrate that the
      autocovariance of markets is correlated with their stability, as well as with
      their state of development. 

PMID- 25383631
TI  - Letter to the editor regarding the article by Dheeman et al., 2014.

PMID- 25383632
TI  - Bioinformatic analysis reveals genome size reduction and the emergence of
      tyrosine phosphorylation site in the movement protein of New World bipartite
      begomoviruses.
AB  - Begomovirus (genus Begomovirus, family Geminiviridae) infection is devastating to
      a wide variety of agricultural crops including tomato, squash, and cassava. Thus,
      understanding the replication and adaptation of begomoviruses has important
      translational value in alleviating substantial economic loss, particularly in
      developing countries. The bipartite genome of begomoviruses prevalent in the New
      World and their counterparts in the Old World share a high degree of genome
      homology except for a partially overlapping reading frame encoding the pre-coat
      protein (PCP, or AV2). PCP contributes to the essential functions of
      intercellular movement and suppression of host RNA silencing, but it is only
      present in the Old World viruses. In this study, we analyzed a set of non
      redundant bipartite begomovirus genomes originating from the Old World (N = 28)
      and the New World (N = 65). Our bioinformatic analysis suggests ~ 120 nucleotides
      were deleted from PCP's proximal promoter region that may have contributed to its
      loss in the New World viruses. Consequently, genomes of the New World viruses are
      smaller than the Old World counterparts, possibly compensating for the loss of
      the intercellular movement functions of PCP. Additionally, we detected
      substantial purifying selection on a portion of the New World DNA-B movement
      protein (MP, or BC1). Further analysis of the New World MP gene revealed the
      emergence of a putative tyrosine phosphorylation site, which likely explains the
      increased purifying selection in that region. These findings provide important
      information about the strategies adopted by bipartite begomoviruses in adapting
      to new environment and suggest future in planta experiments.

PMID- 25383633
TI  - High-resolution gas chromatography/mass spectrometry method for characterization
      and quantitative analysis of ginkgolic acids in Ginkgo biloba plants, extracts,
      and dietary supplements.
AB  - A high-resolution gas chromatography/mass spectrometry (GC/MS) with selected ion
      monitor method focusing on the characterization and quantitative analysis of
      ginkgolic acids (GAs) in Ginkgo biloba L. plant materials, extracts, and
      commercial products was developed and validated. The method involved sample
      extraction with (1:1) methanol and 10% formic acid, liquid-liquid extraction with
      n-hexane, and derivatization with trimethylsulfonium hydroxide (TMSH). Separation
      of two saturated (C13:0 and C15:0) and six unsaturated ginkgolic acid methyl
      esters with different positional double bonds (C15:1 Delta8 and Delta10, C17:1
      Delta8, Delta10, and Delta12, and C17:2) was achieved on a very polar (88%
      cyanopropyl) aryl-polysiloxane HP-88 capillary GC column. The double bond
      positions in the GAs were determined by ozonolysis. The developed GC/MS method
      was validated according to ICH guidelines, and the quantitation results were
      verified by comparison with a standard high-performance liquid chromatography
      method. Nineteen G. biloba authenticated and commercial plant samples and 21
      dietary supplements purported to contain G. biloba leaf extracts were analyzed.
      Finally, the presence of the marker compounds, terpene trilactones and flavonol
      glycosides for Ginkgo biloba in the dietary supplements was determined by
      UHPLC/MS and used to confirm the presence of G. biloba leaf extracts in all of
      the botanical dietary supplements. 

PMID- 25383635
TI  - Positive or negative involvement of heat shock proteins in multiple sclerosis
      pathogenesis: an overview.
AB  - Multiple sclerosis (MS) is the most diffuse chronic inflammatory disease of the
      central nervous system. Both immune-mediated and neurodegenerative processes
      apparently play roles in the pathogenesis of this disease. Heat shock proteins
      (HSPs) are a family of highly evolutionarily conserved proteins; their expression
      in the nervous system is induced in a variety of pathologic states, including
      cerebral ischemia, neurodegenerative diseases, epilepsy, and trauma. To date,
      investigators have observed protective effects of HSPs in a variety of brain
      disease models (e.g. of Alzheimer disease and Parkinson disease). In contrast,
      unequivocal data have been obtained for their roles in MS that depend on the HSP
      family and particularly on their localization (i.e. intracellular or
      extracellular). This article reviews our current understanding of the involvement
      of the principal HSP families in MS. 

PMID- 25383634
TI  - Brain injury in canine models of cardiac surgery.
AB  - Neuropathology and neurologic impairment were characterized in a clinically
      relevant canine model of hypothermic (18 degrees C) circulatory arrest (HCA) and
      cardiopulmonary bypass (CPB). Adult dogs underwent 2 hours of HCA (n = 39), 1
      hour of HCA (n = 20), or standard CPB (n = 22) and survived 2, 8, 24, or 72
      hours. Neurologic impairment and neuropathology were much more severe after 2
      hour HCA than after 1-hour HCA or CPB; histopathology and neurologic deficit
      scores were significantly correlated. Apoptosis developed as early as 2 hours
      after injury and was most severe in the granule cells of the hippocampal dentate
      gyrus. Necrosis evolved more slowly and was most severe in amygdala and pyramidal
      neurons in the cornu ammonis hippocampus. Neuronal injury was minimal up to 24
      hours after 1-hour HCA, but 1 dog that survived to 72 hours showed substantial
      necrosis in the hippocampus, suggesting that, with longer survival time, the
      injury was worse. Although neuronal injury was minimal after CPB, we observed
      rare apoptotic and necrotic neurons in hippocampi and caudate nuclei. These
      results have important implications for CPB in humans and may help explain the
      subtle cognitive changes experienced by patients after CPB.

PMID- 25383636
TI  - Regional ischemic immune myopathy: a paraneoplastic dermatomyopathy.
AB  - Necrosis and regeneration of scattered muscle fibers are common features of many
      active acquired and immune myopathies. We studied a series of patients with
      acquired myopathies with an unusual pattern of regional, rather than scattered,
      muscle fiber necrosis and regeneration. Retrospective review of records of 7
      patients with acquired myopathies having regional muscle fiber necrosis on muscle
      biopsy. Clinical features of patients included proximal symmetric weakness in
      arms and legs with a subacute onset (100%) beginning at ages between 41 and 92
      years, with dysphagia (83%), myalgias (100%), skin rash (67%), and associated
      malignancy (71%). Serum creatine kinase was often very high (>1,600 U/L) (83%).
      Survival was less than 1 year in 43%. Myopathology included a regional
      distribution with muscle fiber necrosis and capillary loss in the border zones
      between intermediate-sized perimysial vessels, vascular pathology with damaged
      walls of intermediate-sized perimysial veins, and connective tissue with
      expression of the ischemia marker carbonic anhydrase IX but no mononuclear cell
      inflammatory foci. These data indicate that regional ischemic immune myopathies
      are likely caused by ischemia in border zones between damaged intermediate-sized
      perimysial blood vessels. Regional ischemic immune myopathies are a distinctive
      pathologic group of acquired, probably immune, noninflammatory dermatomyopathies
      with weakness and often a skin rash and systemic neoplasm. 

PMID- 25383637
TI  - A tick-borne encephalitis model in infant rats infected with langat virus.
AB  - Tick-borne encephalitis virus (TBEV) is the causative agent of human TBE, a
      severe infection that can cause long-lasting neurologic sequelae. Langat virus
      (LGTV), which is closely related to TBEV, has a low virulence for human hosts and
      has been used as a live vaccine against TBEV. Tick-borne encephalitis by natural
      infection of LGTV in humans has not been described, but one of 18,500 LGTV
      vaccinees developed encephalitis. The pathogenetic mechanisms of TBEV are poorly
      understood and, currently, no effective therapy is available. We developed an
      infant rat model of TBE using LGTV as infective agent. Infant Wistar rats were
      inoculated intracisternally with 10 focus-forming units of LGTV and assessed for
      clinical disease and neuropathologic findings at Days 2, 4, 7, and 9 after
      infection. Infection with LGTV led to gait disturbance, hypokinesia, and reduced
      weight gain or weight loss. Cerebrospinal fluid concentrations of RANTES,
      interferon-gamma, interferon-beta, interleukin-6, and monocyte chemotactic
      protein-1 were increased in infected animals. The brains of animals with LGTV
      encephalitis exhibited characteristic perivascular inflammatory cuffs and glial
      nodules; immunohistochemistry documented the presence of LGTV in the thalamus,
      hippocampus, midbrain, frontal pole, and cerebellum. Thus, LGTV
      meningoencephalitis in infant rats mimics important clinical and histopathologic
      features of human TBE. This new model provides a tool to investigate disease
      mechanisms and to evaluate new therapeutic strategies against encephalitogenic
      flaviviruses. 

PMID- 25383638
TI  - Early and persistent expression of phosphorylated alpha-synuclein in the enteric
      nervous system of A53T mutant human alpha-synuclein transgenic mice.
AB  - Alpha-synuclein is a key protein in Parkinson disease (PD) and dementia with Lewy
      bodies. It is found in Lewy bodies in the brains of PD patients and has been
      reported in the peripheral nervous system in postmortem tissues from PD patients
      and in biopsies from patients in the preclinical phase of PD. Here, we used a
      transgenic mouse model of human synucleinopathies expressing the A53T mutant
      alpha-synuclein (TgM83) in which a neurodegenerative process associated with
      alpha-synuclein occurs spontaneously and increases with age. In particular, alpha
      synuclein protein phosphorylated at serine 129 (pSer129 alpha-synuclein)
      naturally and progressively increases in diseased brains. We examined the time
      course of pSer129 alpha-synuclein presence in the gut of these mice between 1.5
      and 22 months of age using immunohistochemistry and paraffin-embedded tissue
      blots. The pSer129 alpha-synuclein accumulated early (before the onset of motor
      signs) and persistently in the enteric nervous system and was concomitantly found
      in the brain. These results suggest that the accumulation of phosphorylated alpha
      synuclein in the enteric and central nervous systems may result from parallel
      pathologic processes when the disease is linked to a mutation of alpha-synuclein.

PMID- 25383640
TI  - Early pathologic changes in hereditary diffuse leukoencephalopathy with
      spheroids.
AB  - Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a familial
      neurodegenerative disease clinically characterized by progressive cognitive and
      motor dysfunction. Mutations in the colony-stimulating factor 1 receptor (CSF1R)
      gene have recently been identified in HDLS patients. The presence of diffuse
      axonal spheroids, myelin loss, and pigmented microglia in the white matter are
      pathologic hallmarks of HDLS; however, early pathologic findings have not been
      described in HDLS patients. We report a Japanese family with HDLS. A novel
      heterozygous c.653 C>Y mutation in the CSF1R gene was identified in the female
      proband who died at the age of 63 years; postmortem findings were compatible with
      HDLS. We also autopsied her sister who was considered to be neurologically
      asymptomatic and died of tuberculosis at the age of 44 years. Postmortem studies
      revealed patchy axonal degeneration and myelin loss, predominantly in the
      subcortical white matter. Pigmented microglia were distributed diffusely
      throughout the cerebral white matter and expressed CSF1R poorly. In conclusion,
      our observations suggest that the pathology of HDLS may initially be
      characterized by multifocal lesions in subcortical white matter regions.
      Moreover, pigmented microglia poorly express CSF1R and are distributed diffusely
      throughout the white matter at the early disease stage, preceding axonal damage
      and myelin loss. 

PMID- 25383639
TI  - The calcium-binding protein EFhd2 modulates synapse formation in vitro and is
      linked to human dementia.
AB  - EFhd2 is a calcium-binding adaptor protein that has been found to be associated
      with pathologically aggregated tau in the brain in Alzheimer disease and in a
      mouse model of frontotemporal dementia. EFhd2 has cell type-specific functions,
      including the modulation of intracellular calcium responses, actin dynamics, and
      microtubule transport. Here we report that EFhd2 protein and mRNA levels are
      reduced in human frontal cortex tissue affected by different types of dementia
      with and without tau pathology. We show that EFhd2 is mainly a neuronal protein
      in the brain and is abundant in the forebrain. Using short hairpin RNA-mediated
      knockdown of EFhd2 expression in cultured cortical neurons, we demonstrate that
      loss of EFhd2 affects the number of synapses developed in vitro whereas it does
      not alter neurite outgrowth per se. Our data suggest that EFhd2 is involved in
      the control of synapse development and maintenance through means other than
      affecting neurite development. The changes in expression levels observed in human
      dementias might, therefore, play a significant role in disease onset and
      progression of dementia, which is characterized by the loss of synapses. 

PMID- 25383641
TI  - Immunoglobulin repertoire of primary lymphomas of the central nervous system.
AB  - Primary lymphoma of the central nervous system (PCNSL) is a diffuse large B-cell
      lymphoma confined to the CNS. It has been hypothesized that antigen(s) in the CNS
      may trigger tumor cell proliferation. Because efforts to identify potential
      antigens have been unsuccessful to date, we studied the B-cell receptor in detail
      in a comprehensive series of 50 PCNSLs to obtain indirect information on
      potential antigens. Potentially functional V-D-J rearrangements were identified
      in all PCNSLs analyzed. Immunoglobulin heavy-chain variable gene segment (IGHV),
      IGHV4, was the predominant family used by 66% (33 of 50) of PCNSLs with a
      preferential rearrangement of the IGHV4-34 gene segment (18 [55%] of 33). The
      IGHV genes showed mutation frequencies from 0% to 29%, with a high average
      mutation frequency of 10%. In addition to 48% (24 of 50) of PCNSLs being highly
      mutated, 22% (11 of 50) defined a low-level mutated group. Antigen selection of
      the tumor cells or their precursors was indicated by replacement/silent mutation
      ratios and ongoing somatic hypermutation. Complementarity determining region 3
      length and composition as well as the lack of stereotyped B-cell receptors
      suggest involvement of several antigens instead of a unique antigen recognized by
      the tumor cells. 

PMID- 25383642
TI  - Imaging of spontaneous ventriculomegaly and vascular malformations in Wistar
      rats: implications for preclinical research.
AB  - Wistar rats are widely used in biomedical research and commonly serve as a model
      organism in neuroscience studies. In most cases when noninvasive imaging is not
      used, studies assume a consistent baseline condition in rats that lack visible
      differences. While performing a series of traumatic brain injury studies, we
      discovered mild spontaneous ventriculomegaly in 70 (43.2%) of 162 Wistar rats
      that had been obtained from 2 different vendors. Advanced magnetic resonance (MR)
      imaging techniques, including MR angiography and diffusion tensor imaging, were
      used to evaluate the rats. Multiple neuropathologic abnormalities, including
      presumed arteriovenous malformations, aneurysms, cysts, white matter lesions, and
      astrogliosis were found in association with ventriculomegaly. Postmortem
      microcomputed tomography and immunohistochemical staining confirmed the presence
      of aneurysms and arteriovenous malformations. Diffusion tensor imaging showed
      significant decreases in fractional anisotropy and increases in mean diffusivity,
      axial diffusivity, and radial diffusivity in multiple white matter tracts (p <
      0.05). These results could impact the interpretation, for example, of a pseudo
      increase of axon integrity and a pseudo-decrease of myelin integrity, based on
      characteristics intrinsic to rats with ventriculomegaly. We suggest the use of
      baseline imaging to prevent the inadvertent introduction of a high degree of
      variability in preclinical studies of neurologic disease or injury in Wistar
      rats. 

PMID- 25383643
TI  - The reliability of the modified lower extremity functional scale among adults
      living with HIV on antiretroviral therapy, in Rwanda, Africa.
AB  - Peripheral neuropathy (PN) is common among people living with HIV (PLHIV) on
      antiretroviral therapy (ART), and affects their daily functional ability and
      quality of life. Lower extremity functional ability, which is most commonly
      compromised in patients with PN, has not been clearly evaluated in an African
      setting, with regard to functional limitations. The lower extremity functional
      scale (LEFS) was originally developed and validated among elderly people in the
      USA, where the environment and activities of daily life are very different from
      those in Rwanda. The purpose of this study was to adapt and establish the
      reliability of LEFS, among adults living with HIV on ART, in a Rwandan
      environment. The study translated LEFS from English to Kinyarwanda, the local
      language spoken in Rwanda, the LEFS was then modified accordingly, and tested for
      test-retest reliability among 50 adult PLHIV on ART. An average Spearman rank
      order correlation coefficient, rho >= 0.7, was considered optimal for
      reliability. Prior to the modification of the LEFS and in the initial testing of
      the translated LEFS, none of the activities was strongly correlated (rho >= 0.8);
      most of the activities (90%, 18/20) were moderately correlated (rho >= 0.5) and
      10% (2/20) were weakly correlated (rho <= 0.5). The rho of most of the functional
      activities improved after modification by an expert group to rho >= 0.7,
      establishing reliability and validity of LEFS among PLHIV on ART with lower
      extremity functional limitations, in this environment. In conclusion, this study
      demonstrated the importance of modifying and establishing test - retest
      reliability of tools derived from developed world contexts to local conditions in
      developing countries, such as in Rwanda. The modified LEFS in this study can be
      used in Rwanda by clinicians, specifically at ART clinics to screen and identify
      people with functional limitations at an early stage of the limitations, for
      treatment, rehabilitation and/or referral to appropriate health care services.

PMID- 25383644
TI  - Structural properties and singular phase transitions of metallic Pr0.50Sr0.50CoO3
      cobaltite.
AB  - The Pr0.50Sr0.50CoO3 perovskite exhibits unique magnetostructural properties
      among the rest of the ferromagnetic/metallic Ln0.50Sr0.50CoO3 compounds. Existing
      reports are largely controversial. We have determined and described its
      structural evolution, which follows the Pm3m -> R3c -> Imma -> I4/mcm
      transformations. The structural changes have been thoroughly described. The
      results are confronted with distinct nonconventional properties and spin-lattice
      coupling effects in another half-doped cobaltite based on praseodymium,
      Pr0.50Ca0.50CoO3. The Imma ->  I4/mcm symmetry change is responsible for the
      unexpected second magnetic transition. 

PMID- 25383645
TI  - Mechanism of Co-C bond photolysis in the base-on form of methylcobalamin.
AB  - A mechanism of Co-C bond photodissociation in the base-on form of the
      methylcobalamin cofactor (MeCbl) has been investigated employing time-dependent
      density functional theory (TD-DFT), in which the key step involves singlet
      radical pair generation from the first electronically excited state (S1). The
      corresponding potential energy surface of the S1 state was constructed as a
      function of Co-C and Co-Naxial bond distances, and two possible photodissociation
      pathways were identified on the basis of energetic grounds. These pathways are
      distinguished by whether the Co-C bond (path A) or Co-Naxial bond (path B)
      elongates first. Although the final intermediate of both pathways is the same
      (namely a ligand field (LF) state responsible for Co-C dissociation), the
      reaction coordinates associated with paths A and B are different. The photolysis
      of MeCbl is wavelength-dependent, and present TD-DFT analysis indicates that
      excitation in the visible alpha/beta band (520 nm) can be associated with path A,
      whereas excitation in the near-UV region (400 nm) is associated with path B. The
      possibility of intersystem crossing, and internal conversion to the ground state
      along path B are also discussed. The mechanism proposed in this study reconciles
      existing experimental data with previous theoretical calculations addressing the
      possible involvement of a repulsive triplet state. 

PMID- 25383646
TI  - Oxidation of rubrene thin films: an electronic structure study.
AB  - The performances of organic semiconductor devices are crucially linked with their
      stability at the ambient atmosphere. The evolution of electronic structures of 20
      nm thick rubrene films exposed to ambient environment with time has been studied
      by UV and X-ray photoemission spectroscopy (UPS and XPS), near edge X-ray
      absorption fine structure (NEXAFS) spectroscopy, and density functional theory
      (DFT). XPS, NEXAFS data, and DFT calculated values suggest the formation of
      rubrene-epoxide and rubrene-endoperoxide through reaction of tetracene backbone
      with oxygen of ambient environment. Angle dependent XPS measurement indicates
      that the entire probed depth of the films reacts with oxygen by spending only
      about 120 min in ambient environment. The HOMO peak of pristine rubrene films
      almost disappears by exposure of 120 min to ambient environment. The evolution of
      the valence band (occupied states) and NEXAFS (unoccupied states) spectra
      indicates that the films become more insulating with exposure as the HOMO-LUMO
      gap increases on oxidation. Oxygen induced chemical reaction completely destroys
      the delocalized nature of the electron distribution in the tetracene backbone of
      rubrene. The results are relevant to the performance and reliability of rubrene
      based devices in the environment. 

PMID- 25383647
TI  - Novel strategies to fight Candida species infection.
AB  - In recent years, there has been a significant increase in the incidence of human
      fungal infections. The increase in cases of infection caused by Candida species,
      and the consequent excessive use of antimicrobials, has favored the emergence of
      resistance to conventional antifungal agents over the past decades. Consequently,
      Candida infections morbidity and mortality are also increasing. Therefore, new
      approaches are needed to improve the outcome of patients suffering from Candida
      infections, because it seems unlikely that the established standard treatments
      will drastically lower the morbidity of mucocutaneous Candida infections and the
      high mortality associated with invasive candidiasis. This review aims to present
      the last advances in the traditional antifungal therapy, and present an overview
      of novel strategies that are being explored for the treatment of Candida
      infections, with a special focus on combined antifungal agents, antifungal
      therapies with alternative compounds (plant extracts and essential oils),
      adjuvant immunotherapy, photodynamic therapy and laser therapy. 

PMID- 25383648
TI  - Trichomonas vaginalis: Clinical relevance, pathogenicity and diagnosis.
AB  - Trichomonas vaginalis is the etiological agent of trichomoniasis, the most
      prevalent non-viral sexually transmitted disease worldwide. Trichomoniasis is a
      widespread, global health concern and occurring at an increasing rate. Infections
      of the female genital tract can cause a range of symptoms, including vaginitis
      and cervicitis, while infections in males are generally asymptomatic. The
      relatively mild symptoms, and lack of evidence for any serious sequelae, have
      historically led to this disease being under diagnosed, and under researched.
      However, growing evidence that T. vaginalis infection is associated with other
      disease states with high morbidity in both men and women has increased the
      efforts to diagnose and treat patients harboring this parasite. The pathology of
      trichomoniasis results from damage to the host epithelia, caused by a variety of
      processes during infection and recent work has highlighted the complex
      interactions between the parasite and host, commensal microbiome and accompanying
      symbionts. The commercial release of a number of nucleic acid amplification tests
      (NAATs) has added to the available diagnostic options. Immunoassay based Point of
      Care testing is currently available, and a recent initial evaluation of a NAAT
      Point of Care system has given promising results, which would enable testing and
      treatment in a single visit. 

PMID- 25383649
TI  - Plant-fungal interactions: What triggers the fungi to switch among lifestyles?
AB  - Up till now various plant-fungal interactions have been extensively studied in
      the form of mycorrhizal, parasitic or endophytic lifestyles. Many of those
      interactions are beneficial to the host plants and a few are detrimental. Several
      investigations have pointed towards the interconversion of one fungal lifestyle
      into another while interact the plant system meaning endophyte may become
      parasite or vice versa. In such case, it is necessary to realize whether these
      different lifestyles are interconnected at some points either by physiological,
      biochemical or molecular routes and to identify the factors that trigger the
      change in fungal lifestyle, which is entirely different than earlier one and
      affects the host plant significantly. This review highlights the possible
      mechanisms of switching among the lifestyles of fungi based on recent findings
      and discusses the factors affecting plant fungal interactions. It also underlines
      the need for studying this important facet of plant-fungal interactions in depth
      which may in future help to fetch more advantages and to avoid the severe
      consequences in agriculture and other related fields. 

PMID- 25383650
TI  - Removal of nitrogen compounds from landfill leachate using reverse osmosis with
      leachate stabilization in a buffer tank.
AB  - In this paper, a removal of nitrogen compounds from a landfill leachate during
      reverse osmosis (RO) was evaluated. The treatment facility consists of a buffer
      tank and a RO system. The removal rate of N?NH4, [Formula: see text] and
      [Formula: see text] in the buffer tank reached 14%, 91% and 41%, respectively.
      The relatively low concentration of organic carbon limits N?NH4 oxidation in the
      buffer tank. The removal rate for the total organic nitrogen (TON) was 47%. The
      removal rate in RO was 99% for [Formula: see text], 84.1% for [Formula: see text]
      and 41% for [Formula: see text]. The accumulation of [Formula: see text] may be
      the result of a low pH, which before the RO process is reduced to a value of 6.0
      6.5. Besides it, the cause for a low removal rate of the [Formula: see text] in
      the buffer tank and during RO may be free ammonia, which can inhibit the
      [Formula: see text] oxidation. The removal rates of total inorganic nitrogen and
      TON in the RO treatment facility were similar being 99% and 98.5%, respectively. 

PMID- 25383652
TI  - Does the severity of psychopathological symptoms mediate the relationship between
      patient personality and therapist response?
AB  - Countertransference can be viewed as a source of valuable diagnostic and
      therapeutic information and plays a crucial role in psychotherapy process and
      outcome. Some empirical researches have showed that patients' specific
      personality characteristics tend to evoke distinct patterns of emotional response
      in clinicians. However, to date there have been no studies examining the impact
      of patients' symptomatology on the association between their personality and
      therapists' responses. This research aimed to (a) investigate the relationship
      between patients' symptom severity and clinicians' emotional responses; and (b)
      explore the possible mediated effect of symptom severity on the relationship
      between patients' personality pathology and countertransference responses. A
      sample of psychiatrists and clinical psychologists (N = 198) of different
      theoretical orientations completed the Shedler-Westen Assessment Procedure-200
      and the Therapist Response Questionnaire on a patient currently in their care,
      who then completed the Symptom Checklist-90-Revised. The findings showed that
      patients' symptomatology partially mediates the relationship between their
      specific personality disorders (in particular, schizotypal, borderline,
      histrionic, and avoidant) and therapists' emotional responses, but in general,
      the impact of symptom severity is less sizable than one aroused by patients'
      personality style. Higher levels of patients' symptom severity are most
      associated with an intense feeling of being overwhelmed, disorganization,
      helplessness, and frustration in clinicians. These countertransference reactions
      are not accounted for by therapists' different therapeutic approaches and other
      variables (as gender, age, profession, and experience). The clinical implications
      of these results are addressed.

PMID- 25383654
TI  - Long-term functional outcome of patients with cerebellar pilocytic astrocytoma
      surgically treated in childhood.
AB  - Abstract Purpose: A number of studies report neurological and cognitive deficits
      and behavioural disorders in children after surgical treatment for a benign
      cerebellar tumour. The present study explores functional outcome in adolescents
      and adults treated for a low-grade cerebellar astrocytoma in childhood. MATERIALS
      AND METHODS: Participants were 18 adolescents and 46 adults treated for low-grade
      astrocytoma in childhood. Academic achievement, professional status and
      neurological, cognitive and behavioural disturbances were collected using self
      completed and parental questionnaires for adolescents and phone interview for
      adults. For the adolescent group, a control group filled in the same
      questionnaires. RESULTS: Mean time lapse from surgery was 7.8 years for
      adolescents and 12.9 years for adults. Five adults (11%) had major sequelae
      related to post-operative complications, post-operative mutism and/or brain stem
      involvement. All the other participants presented close-to-normal academic
      achievement and normal autonomy, despite a high rate of reported cognitive
      difficulties and difficulties related to mild neurological sequelae (fine motor
      skills, balance). CONCLUSION: The long-term functional outcome of low-grade
      cerebellar astrocytoma is generally favourable, in the absence of post-operative
      complications and brain stem involvement. No major impact of neurological
      deficits, cognitive problems and emotional disorders on academic achievement and
      independent functioning was observed.

PMID- 25383653
TI  - Peritoneal tumor carcinomatosis: pharmacological targeting with hyaluronan-based
      bioconjugates overcomes therapeutic indications of current drugs.
AB  - Peritoneal carcinomatosis still lacks reliable therapeutic options. We aimed at
      testing a drug delivery strategy allowing a controlled release of cytotoxic
      molecules and selective targeting of tumor cells. We comparatively assessed the
      efficacy of a loco-regional intraperitoneal treatment in immunocompromised mice
      with bioconjugates formed by chemical linking of paclitaxel or SN-38 to
      hyaluronan, against three models of peritoneal carcinomatosis derived from human
      colorectal, gastric and esophageal tumor cell xenografts. In vitro, bioconjugates
      were selectively internalized through mechanisms largely dependent on interaction
      with the CD44 receptor and caveolin-mediated endocytosis, which led to
      accumulation of compounds into lysosomes of tumor cells. Moreover, they inhibited
      tumor growth comparably to free drugs. In vivo, efficacy of bioconjugates or free
      drugs against luciferase-transduced tumor cells was assessed by bioluminescence
      optical imaging, and by recording mice survival. The intraperitoneal
      administration of bioconjugates in tumor-bearing mice exerted overlapping or
      improved therapeutic efficacy compared with unconjugated drugs. Overall, drug
      conjugation to hyaluronan significantly improved the profiles of in vivo
      tolerability and widened the field of application of existing drugs, over their
      formal approval or current use. Therefore, this approach can be envisaged as a
      promising therapeutic strategy for loco-regional treatment of peritoneal
      carcinomatosis. 

PMID- 25383655
TI  - Serum leptin levels, leptin receptor gene (LEPR) polymorphism, and the risk of
      systemic lupus erythematosus in Kashmiri population.
AB  - The study is conducted to evaluate relationship between LEPRQ223R (Gln > Arg)
      polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE
      risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE
      patients and equal number of healthy control subjects. Leptin and SOb-R levels
      were measured by ELISA assays. The present study showed higher frequency of
      variant genotype (AG + GG) in cases compared to controls [OR = 2.52, CI = 1.18
      5.35, p = 0.03]. Moreover the rare (G) allele was significantly more predominant
      in cases than controls [OR = 1.49, p = 0.04]. Interestingly a positive
      association between the variant genotype and the development of arthritis [OR =
      11.8, CI = 1.6-85.1, p = 0.002] and an inverse association with cardiac disorder
      [OR = 0.09, CI = 0.02-0.46, p = 0.001] was observed in this study. Furthermore
      the study showed significant differences of leptin levels in SLE patients and
      controls (23.9 +/- 19.5 vs 14.8 +/- 10.4, p < 0.001). SLE patients in the highest
      quartile leptin levels (>=32.5 ng/mL) were significantly more likely to have
      higher BMI (p = 0.001) and increased risk of developing arthritis (p = 0.02).
      Furthermore positive association was observed between the variant genotype(AG +
      GG) and leptin levels (p = 0.001) in SLE patients. Thus, it is evident from our
      study that LEPRQ223R polymorphism and elevated leptin levels are associated with
      increased susceptibility of SLE in Kashmiri population. 

PMID- 25383656
TI  - Serous endometrial intraepithelial carcinoma associated with submucosal
      leiomyomatous polyp: The first reported case.

PMID- 25383657
TI  - A method for quantitative analysis of regional lung ventilation using deformable
      image registration of CT and hybrid hyperpolarized gas/1H MRI.
AB  - Hyperpolarized gas magnetic resonance imaging (MRI) generates highly detailed
      maps of lung ventilation and physiological function while CT provides
      corresponding anatomical and structural information. Fusion of such complementary
      images enables quantitative analysis of pulmonary structure-function. However,
      direct image registration of hyperpolarized gas MRI to CT is problematic,
      particularly in lungs whose boundaries are difficult to delineate due to
      ventilation heterogeneity. This study presents a novel indirect method of
      registering hyperpolarized gas MRI to CT utilizing (1)H-structural MR images that
      are acquired in the same breath-hold as the gas MRI. The feasibility of using
      this technique for regional quantification of ventilation of specific pulmonary
      structures is demonstrated for the lobes.The direct and indirect methods of
      hyperpolarized gas MRI to CT image registration were compared using lung images
      from 15 asthma patients. Both affine and diffeomorphic image transformations were
      implemented. Registration accuracy was evaluated using the target registration
      error (TRE) of anatomical landmarks identified on (1)H MRI and CT. The Wilcoxon
      signed-rank test was used to test statistical significance.For the affine
      transformation, the indirect method of image registration was significantly more
      accurate than the direct method (TRE = 14.7 +/- 3.2 versus 19.6 +/- 12.7 mm, p =
      0.036). Using a deformable transformation, the indirect method was also more
      accurate than the direct method (TRE = 13.5 +/- 3.3 versus 20.4 +/- 12.8 mm, p =
      0.006).Accurate image registration is critical for quantification of regional
      lung ventilation with hyperpolarized gas MRI within the anatomy delineated by CT.
      Automatic deformable image registration of hyperpolarized gas MRI to CT via same
      breath-hold (1)H MRI is more accurate than direct registration. Potential
      applications include improved multi-modality image fusion, functionally weighted
      radiotherapy planning, and quantification of lobar ventilation in obstructive
      airways disease.

PMID- 25383658
TI  - Outcome of patients with positive heparin-platelet factor-4 antibodies: A
      retrospective multi-institutional observational study.
AB  - Studies show increased mortality with positive heparin-platelet factor-4 (H-PF4)
      antibodies, especially in hemodialysis patients. We aimed to compare mortality
      and thrombosis in hospitalized patients with positive, equivocal and negative H
      PF4 antibody results. Information was collected on these patients using a multi
      institutional retrospective electronic medical record review. Patients tested for
      H-PF4 antibodies by commercial ELISA during the years 2006 to 2010 were
      identified. We compared 30-day, 90-day and 1-year mortality in patients with
      negative, equivocal and positive H-PF4 test and evaluated the relationship
      between H-PF4 status and rate of thrombosis. Four hundred and seventeen patients
      had ELISA testing for H-PF4 antibodies. Forty-four patients had equivocal
      (optical density value 0.4-0.9) and 21 had positive (value 1) H-PF4 antibody
      test. There were no statistically significant differences in mortality between
      patients with negative, equivocal and positive results at all three time points
      (p = 0.22, 0.27 and 0.38, respectively) even after excluding patients with
      thrombosis (p = 0.22, 0.24 and 0.31, respectively). Age and Charlson score were
      associated with increased 30-day, 90-day and 1 year mortality. Odds ratio of
      having thrombosis was 23.1 for positive vs. equivocal results (p < 0.001);
      however, there was no statistically significant difference between equivocal vs.
      negative results (p = 0.22). Our results revealed no association between H-PF4
      status and mortality, as well as no difference in 1-year survival between the
      positive and negative groups.

PMID- 25383659
TI  - Update of the Phase III trial 'GRETA' of surgery and tamoxifen versus tamoxifen
      alone for early breast cancer in elderly women.
AB  - BACKGROUND: In the Phase III 'GRETA' trial 474 women aged >=70 years with early
      breast cancer were randomly assigned to surgery plus tamoxifen for 5 years or
      tamoxifen alone for 5 years. This is a long-term update. PATIENTS & METHODS:
      Focusing on patients still alive in 2003, outcome end points has been
      recalculated. RESULTS: Median distant metastases disease-free survival is longer
      with tamoxifen alone for 5 years; (48.8 vs 37.9 months; p = 0.009). No difference
      was found in distant metastases rate, disease-free survival, breast cancer and
      overall survival. CONCLUSION: Primary endocrine treatment until the the best
      response, followed by minimal surgery and prosecution endocrine treatment for 5
      10 years is a suitable option for elderly breast cancer patients. Delayed surgery
      does not prejudice overall survival.

PMID- 25383661
TI  - Tungsten-, molybdenum-, and cerium-promoted regioselective and stereospecific
      halogenation of 2,3-epoxy alcohols and 2,3-epoxy sulfonamides.
AB  - The first catalytic regioselective and stereospecific halogenation of 2,3-epoxy
      alcohols and 2,3-epoxy sulfonamides has been developed. Under the catalysis of
      commercially available W- or Mo-salts, complemented by the method using cerium
      halides, the C-3 selective ring opening of structurally diverse epoxides with Cl
      , Br-, and I-nucleophiles afforded various halohydrins in good yields and high
      regioselectivities. 

PMID- 25383660
TI  - Kinetochore motors drive congression of peripheral polar chromosomes by
      overcoming random arm-ejection forces.
AB  - Accurate chromosome segregation during cell division in metazoans relies on
      proper chromosome congression at the equator. Chromosome congression is achieved
      after bi-orientation to both spindle poles shortly after nuclear envelope
      breakdown, or by the coordinated action of motor proteins that slide misaligned
      chromosomes along pre-existing spindle microtubules. These proteins include the
      minus-end-directed kinetochore motor dynein, and the plus-end-directed motors
      CENP-E at kinetochores and chromokinesins on chromosome arms. However, how these
      opposite and spatially distinct activities are coordinated to drive chromosome
      congression remains unknown. Here we used RNAi, chemical inhibition, kinetochore
      tracking and laser microsurgery to uncover the functional hierarchy between
      kinetochore and arm-associated motors, exclusively required for congression of
      peripheral polar chromosomes in human cells. We show that dynein poleward force
      counteracts chromokinesins to prevent stabilization of immature/incorrect end-on
      kinetochore-microtubule attachments and random ejection of polar chromosomes. At
      the poles, CENP-E becomes dominant over dynein and chromokinesins to bias
      chromosome ejection towards the equator. Thus, dynein and CENP-E at kinetochores
      drive congression of peripheral polar chromosomes by preventing arm-ejection
      forces mediated by chromokinesins from working in the wrong direction. 

PMID- 25383662
TI  - Self-powered ultrafast broadband photodetector based on p-n heterojunctions of
      CuO/Si nanowire array.
AB  - A new self-powered broadband photodetector was fabricated by coating an n-silicon
      nanowire (n-Si NW) array with a layer of p-cupric oxide (CuO) nanoflakes through
      a new simple solution synthesis method. The p-n heterojunction shows excellent
      rectification characteristics in the dark and distinctive photovoltaic behavior
      under broadband light illumination. The photoresponse of the detector at zero
      bias voltage shows that this self-powered photodetector is highly sensitive to
      visible and near-infrared light illuminations, with excellent stability and
      reproducibility. Ultrafast response rise and recovery times of 60 and 80 MUs,
      respectively, are shown by the CuO based nanophotodetector. In addition, the
      broadband photodetector can also provide a rapid binary response, with current
      changing from positive to negative upon illumination under a small bias. The
      binary response arises from the photovoltaic behavior and the low turn-on voltage
      of the CuO/Si NW device. These properties make the CuO/Si NW broadband
      photodetector suitable for applications that require high response speeds and
      self-sufficient functionality.

PMID- 25383663
TI  - Rhodium(III)-catalyzed C-H/C-C activation sequence: vinylcyclopropanes as
      versatile synthons in direct C-H allylation reactions.
AB  - Succession of C-H activation and C-C activation was achieved by using a single
      rhodium(III) catalyst. Vinylcyclopropanes were used as versatile coupling
      partners. Mechanistic studies suggest that the olefin insertion step is rate
      determining and a facile beta-carbon elimination is involved, which represents a
      novel ring opening mode of vinylcyclopropanes.

PMID- 25383664
TI  - Evaluation of a clinical video telehealth pain management clinic.
AB  - OBJECTIVES: The objectives of this project were to evaluate patient satisfaction
      with the clinical video telehealth (CVT) pain management clinic, and to evaluate
      possible benefits of this clinic. METHODS: Data collected included the distance
      from the patient's home to the main Department of Veterans Affairs (VA) medical
      center, the distance from the patient's home to the community based outpatient
      clinic (CBOC), travel distance saved for the patient, and travel pay status.
      Following CVT clinic appointments patients were asked to complete a written
      feedback assessment to evaluate patient satisfaction. All data were analyzed
      using descriptive statistics. RESULTS: Veterans saved 8,981 miles in travel
      distance, and the VA saved $2,317.51 due to averted travel reimbursement. There
      was a 90% satisfaction rate with the CVT pain management clinic services, and 90%
      of patients agreed that they would recommend telehealth to other veterans.
      CONCLUSIONS: Overall, patients are satisfied with the CVT pain management clinic.
      Furthermore, the substantial miles saved for the patients, as well as the cost
      savings for the VA, indicates that this service has tangible benefits. As this
      clinic continues to operate, it can be expected that miles saved for patients and
      cost savings for the VA will continue to grow.

PMID- 25383665
TI  - Ultrathin InAs nanowire growth by spontaneous Au nanoparticle spreading on indium
      rich surfaces.
AB  - Ultrathin InAs nanowires (NWs) can enable true one-dimensional electronics. We
      report a growth phenomenon where a bimodal size distribution (~ alpha nm and ~ 5
      nm in diameter) of InAs NWs can be achieved from gold (Au) nanoparticles of a
      single size, alpha (alpha = 50-250 nm). We determine that ultrathin InAs NW
      growth is seeded by ultra-small Au nanoparticles shed from the large Au seeds
      upon indium (In) introduction into the growth system and formed prior to the
      supersaturation of In in Au. The Au spreading phenomenon is explained by the
      balancing of Gibbs free energy lowering from In-Au mixing and the surface tension
      increase. Ultrathin InAs NWs formed in this way exhibit a perfect wurtzite
      structure with no stacking faults. We have observed InAs NWs with diameters down
      to ~ 2 nm using our growth method. Passivating the ultrathin InAs NWs with an
      AlAs shell, subsequently oxidized in air, results in physical deformation of the
      InAs core, demonstrating the mechanical pliability of these ultrathin NWs.

PMID- 25383666
TI  - Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis by
      inhibiting the AKT pathway.
AB  - Inactivation of cell-survival factors is a crucial step in apoptosis. The
      phosphoinositide 3-kinase (PI3K)-AKT signaling pathway promotes cell growth,
      proliferation and survival, and its deregulation causes cancer. How this pathway
      is suppressed to promote apoptosis is poorly understood. Here we report the
      identification of a CED-3 caspase substrate in Caenorhabditis elegans, CNT-1,
      that is cleaved during apoptosis to generate an N-terminal phosphoinositide
      binding fragment (tCNT-1). tCNT-1 translocates from the cytoplasm to the plasma
      membrane and blocks AKT binding to phosphatidylinositol (3,4,5)-trisphosphate,
      thereby disabling AKT activation and its prosurvival activity. Our findings
      reveal a new mechanism that negatively regulates AKT cell signaling to promote
      apoptosis and that may restrict cell growth and proliferation in normal cells. 

PMID- 25383667
TI  - Structural determinants of integrin beta-subunit specificity for latent TGF-beta.
AB  - Eight integrin alpha-beta heterodimers recognize ligands with an Arg-Gly-Asp
      (RGD) motif. However, the structural mechanism by which integrins differentiate
      among extracellular proteins with RGD motifs is not understood. Here, crystal
      structures, mutations and peptide-affinity measurements show that alphaVbeta6
      binds with high affinity to a RGDLXXL/I motif within the prodomains of TGF-beta1
      and TGF-beta3. The LXXL/I motif forms an amphipathic alpha-helix that binds in a
      hydrophobic pocket in the beta6 subunit. Elucidation of the basis for ligand
      binding specificity by the integrin beta subunit reveals contributions by three
      different betaI-domain loops, which we designate specificity-determining loops
      (SDLs) 1, 2 and 3. Variation in a pair of single key residues in SDL1 and SDL3
      correlates with the variation of the entire beta subunit in integrin evolution,
      thus suggesting a paradigmatic role in overall beta-subunit function. 

PMID- 25383668
TI  - Internal motions prime cIAP1 for rapid activation.
AB  - Cellular inhibitor of apoptosis 1 (cIAP1) is a ubiquitin ligase with critical
      roles in the control of programmed cell death and NF-kappaB signaling. Under
      normal conditions, the protein exists as an autoinhibited monomer, but
      proapoptotic signals lead to its dimerization, activation and proteasomal
      degradation. This view of cIAP1 as a binary switch has been informed by static
      structural studies that cannot access the protein's dynamics. Here, we use NMR
      spectroscopy to study micro- and millisecond motions of specific domain
      interfaces in human cIAP1 and use time-resolved small-angle X-ray scattering to
      observe the global conformational changes necessary for activation. Although
      motions within each interface of the 'closed' monomer are insufficient to
      activate cIAP1, they enable associations with catalytic partners and activation
      factors. We propose that these internal motions facilitate rapid peptide-induced
      opening and dimerization of cIAP1, which undergoes a dramatic spring-loaded
      structural transition. 

PMID- 25383669
TI  - Reconstitution of active human core Mediator complex reveals a critical role of
      the MED14 subunit.
AB  - The evolutionarily conserved Mediator complex is a critical coactivator for RNA
      polymerase II (Pol II)-mediated transcription. Here we report the reconstitution
      of a functional 15-subunit human core Mediator complex and its characterization
      by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas
      the reconstituted head and middle modules can stably associate, basal and
      coactivator functions are acquired only after incorporation of MED14 into the
      bimodular complex. This results from a dramatically enhanced ability of MED14
      containing complexes to associate with Pol II. Altogether, our analyses identify
      MED14 as both an architectural and a functional backbone of the Mediator complex.
      We further establish a conditional requirement for metazoan-specific MED26 that
      becomes evident in the presence of heterologous nuclear factors. This general
      approach paves the way for systematic dissection of the multiple layers of
      functionality associated with the Mediator complex. 

PMID- 25383671
TI  - Platelet transfusion: a clinical practice guideline from the AABB.
AB  - BACKGROUND: The AABB (formerly, the American Association of Blood Banks)
      developed this guideline on appropriate use of platelet transfusion in adult
      patients. METHODS: These guidelines are based on a systematic review of
      randomized, clinical trials and observational studies (1900 to September 2014)
      that reported clinical outcomes on patients receiving prophylactic or therapeutic
      platelet transfusions. An expert panel reviewed the data and developed
      recommendations using the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) framework. RECOMMENDATION 1: The AABB recommends that
      platelets should be transfused prophylactically to reduce the risk for
      spontaneous bleeding in hospitalized adult patients with therapy-induced
      hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized
      adult patients with a platelet count of 10 * 109 cells/L or less to reduce the
      risk for spontaneous bleeding. The AABB recommends transfusing up to a single
      apheresis unit or equivalent. Greater doses are not more effective, and lower
      doses equal to one half of a standard apheresis unit are equally effective.
      (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: The
      AABB suggests prophylactic platelet transfusion for patients having elective
      central venous catheter placement with a platelet count less than 20 * 109
      cells/L. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3:
      The AABB suggests prophylactic platelet transfusion for patients having elective
      diagnostic lumbar puncture with a platelet count less than 50 * 109 cells/L.
      (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 4: The
      AABB suggests prophylactic platelet transfusion for patients having major
      elective nonneuraxial surgery with a platelet count less than 50 * 109 cells/L.
      (Grade: weak recommendation; very-low-quality evidence). RECOMMENDATION 5: The
      AABB recommends against routine prophylactic platelet transfusion for patients
      who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass.
      The AABB suggests platelet transfusion for patients having bypass who exhibit
      perioperative bleeding with thrombocytopenia and/or evidence of platelet
      dysfunction. (Grade: weak recommendation; very-low-quality evidence).
      RECOMMENDATION 6: The AABB cannot recommend for or against platelet transfusion
      for patients receiving antiplatelet therapy who have intracranial hemorrhage
      (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality
      evidence).

PMID- 25383670
TI  - BRD4 assists elongation of both coding and enhancer RNAs by interacting with
      acetylated histones.
AB  - Small-molecule BET inhibitors interfere with the epigenetic interactions between
      acetylated histones and the bromodomains of the BET family proteins, including
      BRD4, and they potently inhibit growth of malignant cells by targeting cancer
      promoting genes. BRD4 interacts with the pause-release factor P-TEFb and has been
      proposed to release RNA polymerase II (Pol II) from promoter-proximal pausing. We
      show that BRD4 occupies widespread genomic regions in mouse cells and directly
      stimulates elongation of both protein-coding transcripts and noncoding enhancer
      RNAs (eRNAs), in a manner dependent on bromodomain function. BRD4 interacts with
      elongating Pol II complexes and assists Pol II in progression through
      hyperacetylated nucleosomes by interacting with acetylated histones via
      bromodomains. On active enhancers, the BET inhibitor JQ1 antagonizes BRD4
      associated eRNA synthesis. Thus, BRD4 is involved in multiple steps of the
      transcription hierarchy, primarily by facilitating transcript elongation both at
      enhancers and on gene bodies independently of P-TEFb. 

PMID- 25383672
TI  - A new mode to light up an adjacent DNA-scaffolded silver probe pair and its
      application for specific DNA detection.
AB  - By fluorescence enhancement of a proximity-dependent DNA-scaffolded silver
      nanocluster probe pair and exonuclease III-mediated signal amplification, we
      present a new fluorescence turn-on mode and its application for specific DNA
      detection. 

PMID- 25383673
TI  - Hunting the needle in the haystack: a guide to obtain biologically meaningful
      microRNA targets.
AB  - MicroRNAs (miRNAs) are endogenous small non-coding RNAs of ~23 nucleotides in
      length that form up a novel class of regulatory determinants, with a large set of
      target mRNAs postulated for every single miRNA. Thousands of miRNAs have been
      discovered so far, with hundreds of them shown to govern biological processes
      with impact on disease. However, very little is known about how they specifically
      interfere with biological pathways and disease mechanisms. To investigate this
      interaction, the hunt for direct miRNA targets that mediate the miRNA effects-
      the "needle in the haystack"--is an essential step. In this review we provide a
      comprehensive workflow of successfully applied methods starting from the
      identification of putative miRNA-target pairs, followed by validation of direct
      miRNA-mRNA interactions, and finally presenting methods that dissect the impact
      of particular miRNA-target pairs on a biological process or disease. This guide
      allows the way to be paved for obtaining biologically meaningful miRNA targets.

PMID- 25383674
TI  - Nrf2 and redox status in prediabetic and diabetic patients.
AB  - The redox status associated with nuclear factor erythroid 2-related factor-2
      (Nrf2) was evaluated in prediabetic and diabetic subjects. Total antioxidant
      status (TAS) in plasma and erythrocytes, glutathione (GSH) and malondialdehyde
      (MDA) content and activity of antioxidant enzymes were measured as redox status
      markers in 259 controls, 111 prediabetics and 186 diabetic type 2 subjects. Nrf2
      was measured in nuclear extract fractions from peripheral blood mononuclear cells
      (PBMC). Nrf2 levels were lower in prediabetic and diabetic patients. TAS, GSH and
      activity of glutamate cysteine ligase were lower in diabetic subjects. An
      increase of MDA and superoxide dismutase activity was found in diabetic subjects.
      These results suggest that low levels of Nrf2 are involved in the development of
      oxidative stress and redox status disbalance in diabetic patients. 

PMID- 25383675
TI  - Post-transcriptional up-regulation of PDGF-C by HuR in advanced and stressed
      breast cancer.
AB  - Breast cancer is a heterogeneous disease characterized by multiple genetic
      alterations leading to the activation of growth factor signaling pathways that
      promote cell proliferation. Platelet-derived growth factor-C (PDGF-C) is
      overexpressed in various malignancies; however, the involvement of PDGF-C in
      breast cancers and the mechanisms underlying PDGF-C deregulation remain unclear.
      Here, we show that PDGF-C is overexpressed in clinical breast cancers and
      correlates with poor prognosis. PDGF-C up-regulation was mediated by the human
      embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C
      transcript by binding to two predicted AU-rich elements (AREs) in the 3'
      untranslated region (3'-UTR). HuR is up-regulated in hydrogen peroxide-treated or
      ultraviolet-irradiated breast cancer cells. Clinically, HuR levels are correlated
      with PDGF-C expression and histological grade or pathological tumor-node
      metastasis (pTNM) stage. Our findings reveal a novel mechanism underlying HuR
      mediated breast cancer progression, and suggest that HuR and PDGF-C are potential
      molecular candidates for targeted therapy of breast cancers. 

PMID- 25383676
TI  - Structural biology of DNA (6-4) photoproducts formed by ultraviolet radiation and
      interactions with their binding proteins.
AB  - Exposure to the ultraviolet component of sunlight causes DNA damage, which
      subsequently leads to mutations, cellular transformation, and cell death. DNA
      photoproducts with (6-4) pyrimidine-pyrimidone adducts are more mutagenic than
      cyclobutane pyrimidine dimers. These lesions must be repaired because of the high
      mutagenic potential of (6-4) photoproducts. We here reviewed the structures of (6
      4) photoproducts, particularly the detailed structures of the (6-4) lesion and (6
      4) lesion-containing double-stranded DNA. We also focused on interactions with
      their binding proteins such as antibody Fabs, (6-4) photolyase, and nucleotide
      excision repair protein. The (6-4) photoproducts that bound to these proteins had
      common structural features: The 5'-side thymine and 3'-side pyrimidone bases of
      the T(6-4)T segment were in half-chair and planar conformations, respectively,
      and both bases were positioned nearly perpendicularly to each other. Interactions
      with binding proteins showed that the DNA helices flanking the T(6-4)T segment
      were largely kinked, and the flipped-out T(6-4)T segment was recognized by these
      proteins. These proteins had distinctive binding-site structures that were
      appropriate for their functions. 

PMID- 25383677
TI  - alpha, omega-Cholesterol-functionalized low molecular weight polyethylene glycol
      as a novel modifier of cationic liposomes for gene delivery.
AB  - Here, three novel cholesterol (Ch)/low molecular weight polyethylene glycol (PEG)
      conjugates, termed alpha, omega-cholesterol-functionalized PEG (Ch2-PEGn), were
      successfully synthesized using three kinds of PEG with different average
      molecular weight (PEG600, PEG1000 and PEG2000). The purpose of the study was to
      investigate the potential application of novel cationic liposomes (Ch2-PEGn-CLs)
      containing Ch2-PEGn in gene delivery. The introduction of Ch2-PEGn affected both
      the particle size and zeta potential of cationic liposomes. Ch2-PEG2000
      effectively compressed liposomal particles and Ch2-PEG2000-CLs were of the
      smallest size. Ch2-PEG1000 and Ch2-PEG2000 significantly decreased zeta
      potentials of Ch2-PEGn-CLs, while Ch2-PEG600 did not alter the zeta potential due
      to the short PEG chain. Moreover, the in vitro gene transfection efficiencies
      mediated by different Ch2-PEGn-CLs also differed, in which Ch2-PEG600-CLs
      achieved the strongest GFP expression than Ch2-PEG1000-CLs and Ch2-PEG2000-CLs in
      SKOV-3 cells. The gene delivery efficacy of Ch2-PEGn-CLs was further examined by
      addition of a targeting moiety (folate ligand) in both folate-receptor (FR)
      overexpressing SKOV-3 cells and A549 cells with low expression of FR. For Ch2
      PEG1000-CLs and Ch2-PEG2000-CLs, higher molar ratios of folate ligand resulted in
      enhanced transfection efficacies, but Ch2-PEG600-CLs had no similar in contrast.
      Additionally, MTT assay proved the reduced cytotoxicities of cationic liposomes
      after modification by Ch2-PEGn. These findings provide important insights into
      the effects of Ch2-PEGn on cationic liposomes for delivering genes, which would
      be beneficial for the development of Ch2-PEGn-CLs-based gene delivery system. 

PMID- 25383678
TI  - Circulating microRNA-19a as a potential novel biomarker for diagnosis of acute
      myocardial infarction.
AB  - Acute myocardial infarction (AMI) is a serious cardiovascular disease.
      Investigating new susceptibility genes for effective methods of early diagnosis
      of AMI is important. In the current study, peripheral blood miR-19a levels were
      detected by real-time polymerase chain reaction. Significant differences and
      logistic correlation analyses were carried out by grouping of disease types and
      stratification of risk factors. Receiver-operator characteristic curve analysis
      was used to compare the current common clinical biochemical markers and evaluate
      the sensitivity and specificity of miR-19a for diagnosing AMI. Circulating miR
      19a expression in the AMI group was higher than that in controls. The diagnostic
      effect of circulating miR-19a levels was superior to current clinical biochemical
      indices, such as CK, CK-MB, MYO, hs-TnI, and BNP. Our results show that there is
      a close association of circulating miR-19a levels with susceptibility to AMI.
      Circulating miR-19a levels could be a candidate diagnostic biomarker for AMI. 

PMID- 25383679
TI  - Interactions of borneol with DPPC phospholipid membranes: a molecular dynamics
      simulation study.
AB  - Borneol, known as a "guide" drug in traditional Chinese medicine, is widely used
      as a natural penetration enhancer in modern clinical applications. Despite a
      large number of experimental studies on borneol's penetration enhancing effect,
      the molecular basis of its action on bio-membranes is still unclear. We carried
      out a series of coarse-grained molecular dynamics simulations with the borneol
      concentration ranging from 3.31% to 54.59% (v/v, lipid-free basis) to study the
      interactions of borneol with aDPPC(1,2-dipalmitoylsn-glycero-3
      phosphatidylcholine) bilayer membrane, and the temperature effects were also
      considered. At concentrations below 21.89%, borneol's presence only caused DPPC
      bilayer thinning and an increase in fluidity; A rise in temperature could promote
      the diffusing progress of borneol. When the concentration was 21.89% or above,
      inverted micelle-like structures were formed within the bilayer interior, which
      led to increased bilayer thickness, and an optimum temperature was found for the
      interaction of borneol with the DPPC bilayer membrane. These findings revealed
      that the choice of optimal concentration and temperature is critical for a given
      application in which borneol is used as a penetration enhancer. Our results not
      only clarify some molecular basis for borneol's penetration enhancing effects,
      but also provide some guidance for the development and applications of new
      preparations containing borneol. 

PMID- 25383681
TI  - The discovery of aurora kinase inhibitor by multi-docking-based virtual
      screening.
AB  - We report the discovery of aurora kinase inhibitor using the fragment-based
      virtual screening by multi-docking strategy. Among a number of fragments
      collected from eMololecules, we found four fragment molecules showing potent
      activity (>50% at 100 MUM) against aurora kinase. Based on the explored fragment
      scaffold, we selected two compounds in our synthesized library and validated the
      biological activity against Aurora kinase. 

PMID- 25383680
TI  - Pine bark and green tea concentrated extracts: antioxidant activity and
      comprehensive characterization of bioactive compounds by HPLC-ESI-QTOF-MS.
AB  - The consumption of polyphenols has frequently been associated with low incidence
      of degenerative diseases. Most of these natural antioxidants come from fruits,
      vegetables, spices, grains and herbs. For this reason, there has been increasing
      interest in identifying plant extract compounds. Polymeric tannins and monomeric
      flavonoids, such as catechin and epicatechin, in pine bark and green tea extracts
      could be responsible for the higher antioxidant activities of these extracts. The
      aim of the present study was to characterize the phenolic compounds in pine bark
      and green tea concentrated extracts using high-performance liquid chromatography
      coupled to electrospray ionization mass spectrometry (HPLC-ESI-QTOF-MS). A total
      of 37 and 35 compounds from pine bark and green tea extracts, respectively, were
      identified as belonging to various structural classes, mainly flavan-3-ol and its
      derivatives (including procyanidins). The antioxidant capacity of both extracts
      was evaluated by three complementary antioxidant activity methods: Trolox
      equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP)
      and oxygen radical absorbance capacity (ORAC). Higher antioxidant activity values
      by each method were obtained. In addition, total polyphenol and flavan-3-ol
      contents, which were determined by Folin-Ciocalteu and vanillin assays,
      respectively, exhibited higher amounts of gallic acid and (+)-catechin
      equivalents. 

PMID- 25383682
TI  - Motives and characteristics of domestic violence homicides and suicides among
      women in India.
AB  - Domestic violence homicides and suicides are significant causes of deaths among
      women in India. This study examined characteristics and motives of various types
      of domestic violence-related homicides and suicides (n = 100) in India using
      newspaper reports (2011-2012). The majority of victims were found to be young
      women, mostly killed by burning or strangulation methods. The most frequently
      reported motive was dowry demands followed by a history of domestic violence or
      harassment and family conflict. The findings highlight the need for stronger
      prevention/intervention programs in India to identify and intervene with women at
      high risk for being killed or committing suicide. 

PMID- 25383683
TI  - Ensuring access to the appropriate health care professionals: regionalization and
      centralization of care in a new era of health care financing and delivery.

PMID- 25383684
TI  - Generalized ratiometric indicator based surface-enhanced Raman spectroscopy for
      the detection of Cd(2+) in environmental water samples.
AB  - The concept of generalized ratiometric indicator based surface-enhanced Raman
      spectroscopy was first introduced and successfully implemented in the detection
      of Cd(2+) in environmental water samples using Au nanoparticles (AuNPs) modified
      by trithiocyanuric acid (TMT). Without the use of any internal standard, the
      proposed method achieved accurate concentration predictions for Cd(2+) in
      environmental water samples with recoveries in the ranges of 91.8-108.1%,
      comparable to the corresponding values obtained by atomic absorption
      spectroscopy. The limit of detection and limit of quantification were estimated
      to be 2.9 and 8.7 nM, respectively. More importantly, other species present in
      water samples which cannot react with TMT and have weaker binding ability to
      AuNPs than TMT do not interfere with the quantification of Cd(2+). Therefore, it
      is expected that the combination of the generalized ratiometric indicator based
      surface-enhanced Raman spectroscopy with the proposed AuNP-TMT probing system can
      be a competitive alternative for the primary screening of Cd(2+) pollution. 

PMID- 25383685
TI  - [Pediatric tracheostomy: a ten-year analysis in the Intensive Care Unit of Sancti
      Spiritus ?Jose Marti? Pediatric Teaching Hospital].
AB  - INTRODUCTION: There has been a significant change in the role of pediatric
      tracheostomy over the last twenty years. Obstruction of the upper airway caused
      by infectious agents is no longer the leading cause of tracheostomy in children.
      Structural anomalies of the upper airway as well as the need for prolonged
      ventilator assistance have become the most frequent indication for pediatric
      tracheostomy. OBJECTIVE: The purpose of this paper is to assess the incidence,
      indications, complications, and role in mortality of tracheostomy in our
      pediatric population. METHODS: A retrospective descriptive study of pediatric
      patients who underwent tracheostomy was conducted between 1999 and 2008 in the
      Pediatric Intensive Care Unit of the Jose Marti de Sancti Spiritus Pediatric
      Teaching Hospital in Cuba. RESULTS: Tracheostomy was performed in 14 patients
      during the period of the study (0.5% of admitted patients). Nine of them (64.2%)
      were younger than one year. The most frequent indication for the procedure was
      the need for prolonged mechanical ventilation in patients with neurologic
      disorders in 10 patients (71.42%). Upper airway malformations and acute
      infections were infrequent indications for tracheostomy. The most frequent
      complications were infectious in 10 patients (71.4%) and obstruction in four
      patients (28.5%). The following germs were found: Pseudomona aeruginosa in six
      patients (60%), Staphylococcus aureus in three patients (30%), and Enterobacter
      cloacae in three patients (30%). Furthermore, four patients were successfully
      decannulated (28.5%), five patients died (35.7%) but only in one (7.14%), death
      could be attributed to tracheostomy. CONCLUSION: The need for prolonged
      mechanical ventilation in patients with neurologic disorders was the main
      indication for tracheostomy in our pediatric population; most of these children
      were younger than one year. The procedure had little impact in overall mortality
      in this group of patients.

PMID- 25383686
TI  - Learning to act on secondhand tobacco smoke exposure to limit risk for coronary
      heart disease.

PMID- 25383688
TI  - Contrasting regeneration strategies in climax and long-lived pioneer tree species
      in a subtropical forest.
AB  - 1: This study investigated 15 coexisting dominant species in a humid subtropical
      evergreen broad-leaved forest in southwest China, consisting of long-lived
      pioneers and climax species occurring in natural and disturbed regimes. The
      authors hypothesized that there would be non-tradeoff scaling relationships
      between sprouting and seed size among species, with the aim of uncovering the
      ecological relationship between plant sprouting and seed characteristics in the
      two functional groups. 2: The sprouting variations of the species were initially
      examined using pairwise comparisons between natural and disturbed habitats within
      and across species and were noted to show a continuum in persistence niches
      across the forest dominants, which may underlie the maintenance of plant
      diversity. Second, a significantly positive, rather than tradeoff, relationship
      between sprout number and seed size across species within each of the two
      functional groups was observed, and an obvious elevational shift with a common
      slope among the two groups in their natural habitat was examined. The results
      indicate the following: 1) the relationship of seed size vs. sprouts in the
      natural habitat is more likely to be bet-hedging among species within a guild in
      a forest; 2) climax species tend to choose seeding rather than sprouting
      regeneration, and vice versa for the long-lived pioneers; and 3) the negative
      correlation between sprouting and seed dispersal under disturbed conditions may
      imply a tradeoff between dispersal and persistence in situ during the process of
      plant regeneration. 3: These findings may be of potential significance for urban
      greening using native species. 

PMID- 25383687
TI  - Non-scanning fiber-optic near-infrared beam led to two-photon optogenetic
      stimulation in-vivo.
AB  - Stimulation of specific neurons expressing opsins in a targeted region to
      manipulate brain function has proved to be a powerful tool in neuroscience.
      However, the use of visible light for optogenetic stimulation is invasive due to
      low penetration depth and tissue damage owing to larger absorption and
      scattering. Here, we report, for the first time, in-depth non-scanning fiber
      optic two-photon optogenetic stimulation (FO-TPOS) of neurons in-vivo in
      transgenic mouse models. In order to optimize the deep-brain stimulation
      strategy, we characterized two-photon activation efficacy at different near
      infrared laser parameters. The significantly-enhanced in-depth stimulation
      efficiency of FO-TPOS as compared to conventional single-photon beam was
      demonstrated both by experiments and Monte Carlo simulation. The non-scanning FO
      TPOS technology will lead to better understanding of the in-vivo neural circuitry
      because this technology permits more precise and less invasive anatomical
      delivery of stimulation. 

PMID- 25383689
TI  - Promoting prosocial behavior and self-regulatory skills in preschool children
      through a mindfulness-based Kindness Curriculum.
AB  - Self-regulatory abilities are robust predictors of important outcomes across the
      life span, yet they are rarely taught explicitly in school. Using a randomized
      controlled design, the present study investigated the effects of a 12-week
      mindfulness-based Kindness Curriculum (KC) delivered in a public school setting
      on executive function, self-regulation, and prosocial behavior in a sample of 68
      preschool children. The KC intervention group showed greater improvements in
      social competence and earned higher report card grades in domains of learning,
      health, and social-emotional development, whereas the control group exhibited
      more selfish behavior over time. Interpretation of effect sizes overall indicate
      small to medium effects favoring the KC group on measures of cognitive
      flexibility and delay of gratification. Baseline functioning was found to
      moderate treatment effects with KC children initially lower in social competence
      and executive functioning demonstrating larger gains in social competence
      relative to the control group. These findings, observed over a relatively short
      intervention period, support the promise of this program for promoting self
      regulation and prosocial behavior in young children. They also support the need
      for future investigation of program implementation across diverse settings.

PMID- 25383690
TI  - The association of maternal socialization in childhood and adolescence with adult
      offsprings' sympathy/caring.
AB  - The purpose of the study was to examine associations between mothers'
      socialization practices in childhood and adolescence and offsprings' (N = 32, 16
      female) sympathy/concern in early adulthood. Mothers reported on their
      socialization practices and beliefs a total of 6 times using a Q-sort during
      their offsprings' childhood (between 7-8 and 11-12 years of age) and adolescence
      (between 13-14 and 17-18 years of age). Adult offsprings' sympathy/caring was
      assessed 3 times in early adulthood (at ages 19-20 to 23-24 years) and in their
      mid-20s to 30s (ages 25-26 to 31-32 years). In general, friends' reports of
      participants' sympathy/concern at ages 25-32 years related positively to mother
      reported rational discipline (including inductions) and warmth and support during
      childhood and adolescence and negatively to mother-reported negative affect
      during adolescence. Self-reported sympathy/concern during early adulthood was
      positively related to maternal warmth and support during childhood and almost
      significantly negatively related to mother-reported negative affect during
      childhood and adolescence. Most of the relations held when the prior level of
      self-reported childhood empathy or adolescent sympathy was controlled.

PMID- 25383691
TI  - Chroman-4-one- and chromone-based sirtuin 2 inhibitors with antiproliferative
      properties in cancer cells.
AB  - Sirtuins (SIRTs) catalyze the NAD(+)-dependent deacetylation of N(epsilon)-acetyl
      lysines on various protein substrates. SIRTs are interesting drug targets as they
      are considered to be related to important pathologies such as inflammation and
      aging-associated diseases. We have previously shown that chroman-4-ones act as
      potent and selective inhibitors of SIRT2. Herein we report novel chroman-4-one
      and chromone-based SIRT2 inhibitors containing various heterofunctionalities to
      improve pharmacokinetic properties. The compounds retained both high SIRT2
      selectivity and potent inhibitory activity. Two compounds were tested for their
      antiproliferative effects in breast cancer (MCF-7) and lung carcinoma (A549) cell
      lines. Both compounds showed antiproliferative effects correlating with their
      SIRT2 inhibition potency. They also increased the acetylation level of alpha
      tubulin, indicating that SIRT2 is likely to be the target in cancer cells. A
      binding mode of the inhibitors that is consistent with the SAR data was proposed
      based on a homology model of SIRT2. 

PMID- 25383692
TI  - Evaluating the benefits of commercial building energy codes and improving federal
      incentives for code adoption.
AB  - The federal government has the goal of decreasing commercial building energy
      consumption and pollutant emissions by incentivizing the adoption of commercial
      building energy codes. Quantitative estimates of code benefits at the state level
      that can inform the size and allocation of these incentives are not available. We
      estimate the state-level climate, environmental, and health benefits (i.e.,
      social benefits) and reductions in energy bills (private benefits) of a more
      stringent code (ASHRAE 90.1-2010) relative to a baseline code (ASHRAE 90.1-2007).
      We find that reductions in site energy use intensity range from 93 MJ/m(2) of new
      construction per year (California) to 270 MJ/m(2) of new construction per year
      (North Dakota). Total annual benefits from more stringent codes total $506
      million for all states, where $372 million are from reductions in energy bills,
      and $134 million are from social benefits. These total benefits range from $0.6
      million in Wyoming to $49 million in Texas. Private benefits range from $0.38 per
      square meter in Washington State to $1.06 per square meter in New Hampshire.
      Social benefits range from $0.2 per square meter annually in California to $2.5
      per square meter in Ohio. Reductions in human/environmental damages and future
      climate damages account for nearly equal shares of social benefits. 

PMID- 25383694
TI  - Poroelastic theory applied to the adsorption-induced deformation of vitreous
      silica.
AB  - When vitreous silica is submitted to high pressures under a helium atmosphere,
      the change in volume observed is much smaller than expected from its elastic
      properties. It results from helium penetration into the interstitial free volume
      of the glass network. We present here the results of concurrent spectroscopic
      experiments using either helium or neon and molecular simulations relating the
      amount of gas adsorbed to the strain of the network. We show that a generalized
      poromechanical approach, describing the elastic properties of microporous
      materials upon adsorption, can be applied successfully to silica glass in which
      the free volume exists only at the subnanometer scale. In that picture, the
      adsorption-induced deformation accounts for the small apparent compressibility of
      silica observed in experiments. 

PMID- 25383693
TI  - Taste and physiological responses to glucosinolates: seed predator versus seed
      disperser.
AB  - In contrast to most other plant tissues, fleshy fruits are meant to be eaten in
      order to facilitate seed dispersal. Although fleshy fruits attract consumers,
      they may also contain toxic secondary metabolites. However, studies that link the
      effect of fruit toxins with seed dispersal and predation are scarce.
      Glucosinolates (GLSs) are a family of bitter-tasting compounds. The fleshy fruit
      pulp of Ochradenus baccatus was previously found to harbor high concentrations of
      GLSs, whereas the myrosinase enzyme, which breaks down GLSs to produce foul
      tasting chemicals, was found only in the seeds. Here we show the differential
      behavioral and physiological responses of three rodent species to high dose (80%)
      Ochradenus' fruits diets. Acomys russatus, a predator of Ochradenus' seeds, was
      the least sensitive to the taste of the fruit and the only rodent to exhibit
      taste-related physiological adaptations to deal with the fruits' toxins. In
      contrast, Acomys cahirinus, an Ochradenus seed disperser, was more sensitive to a
      diet containing the hydrolyzed products of the GLSs. A third rodent (Mus
      musculus) was deterred from Ochradenus fruits consumption by the GLSs and their
      hydrolyzed products. We were able to alter M. musculus avoidance of whole fruit
      consumption by soaking Ochradenus fruits in a water solution containing 1%
      adenosine monophosphate, which blocks the bitter taste receptor in mice. The
      observed differential responses of these three rodent species may be due to
      evolutionary pressures that have enhanced or reduced their sensitivity to the
      taste of GLSs. 

PMID- 25383696
TI  - Benzotriazole ultraviolet stabilizers show potent activities as human aryl
      hydrocarbon receptor ligands.
AB  - Benzotriazole ultraviolet stabilizers (BUVSs) used in consumer products are
      raising concerns as new pollutants in the aquatic environment. We determined the
      agonistic activities of eight BUVSs and a chemically distinct UV absorber (4
      methylbenzylidinecamphor) toward the human aryl hydrocarbon receptor (AhR) and
      thyroid hormone receptors alpha and beta. Although none of the BUVSs showed
      ligand activity against the thyroid hormone receptors, four of them (UV-P, UV-9,
      UV-326, and UV-090) showed significant AhR ligand activity. Their half-maximal
      effective concentrations (EC50) were 130 nM for UV-P, 460 nM for UV-9, and 5.1
      MUM for UV-090 (a value for UV-326 could not be determined). Of the numerous AhR
      ligands, it is well-known that those considered nontoxic are quickly metabolized
      by enzymes such as CYP1A1, which destroys their ability to function as ligands.
      Accordingly, we established a new yeast assay for simultaneous monitoring of both
      the strength of AhR ligand activity and ligand degradation by CYP1A1. We found
      the AhR ligand activities of the above four BUVSs to be stable in the presence of
      CYP1A1; therefore, they have the potential to accumulate and exert potent
      physiological effects in humans, analogous to polycyclic aromatic hydrocarbons
      and dioxins, which are known stable and toxic ligands. 

PMID- 25383697
TI  - Response to the letter to the editor regarding our article (Dheeman et al.,
      2014).

PMID- 25383698
TI  - Design and operation of the National Survey of Children with Special Health Care
      Needs, 2009-2010.
AB  - OBJECTIVES: This report presents the development, plan, and operation of the 2009
      2010 National Survey of Children with Special Health Care Needs, a module of the
      State and Local Area Integrated Telephone Survey. The survey is conducted by the
      Centers for Disease Control and Prevention's National Center for Health
      Statistics. This survey was designed to produce national and state-specific
      prevalence estimates of children with special health care needs (CSHCN), to
      describe the types of services that they need and use, and to assess aspects of
      the system of care for CSHCN. METHODS: A random-digit-dial sample of households
      with children under age 18 years was constructed for each of the 50 states and
      the District of Columbia. The sampling frame consisted of landline phone numbers
      and cellular(cell) phone numbers of households that reported a cell-phone-only or
      cell-phone-mainly status. Children in identified households were screened for
      special health care needs. If CSHCN were identified in the household, a detailed
      interview was conducted for one randomly selected child with special health care
      needs. Respondents were parents or guardians who knew about the children's health
      and health care. RESULTS: A total of 196,159 household screening interviews were
      completed from July 2009 through March 2011, resulting in 40,242 completed
      special-needs interviews, including 2,991 from cell-phone interviews. The
      weighted overall response rate was 43.7% for the landline sample, 15.2% for the
      cell-phone sample, and 25.5% overall.

PMID- 25383700
TI  - Switching individual quantum dot emission through electrically controlling
      resonant energy transfer to graphene.
AB  - Electrically controlling resonant energy transfer of optical emitters provides a
      novel mechanism to switch nanoscale light sources on and off individually for
      optoelectronic applications. Graphene's optical transitions are tunable through
      electrostatic gating over a broad wavelength spectrum, making it possible to
      modulate energy transfer from a variety of nanoemitters to graphene at room
      temperature. We demonstrate photoluminescence switching of individual colloidal
      quantum dots by electrically tuning their energy transfer to graphene. The gate
      dependence of energy transfer modulation confirms that the transition occurs when
      the Fermi level is shifted over half the emitter's excitation energy. The
      modulation magnitude decreases rapidly with increasing emitter-graphene distance
      (d), following the 1/d(4) rate trend unique to the energy transfer process to two
      dimensional materials. 

PMID- 25383699
TI  - Amino acid sequence of anionic peroxidase from the windmill palm tree
      Trachycarpus fortunei.
AB  - Palm peroxidases are extremely stable and have uncommon substrate specificity.
      This study was designed to fill in the knowledge gap about the structures of a
      peroxidase from the windmill palm tree Trachycarpus fortunei. The complete amino
      acid sequence and partial glycosylation were determined by MALDI-top-down
      sequencing of native windmill palm tree peroxidase (WPTP), MALDI-TOF/TOF MS/MS of
      WPTP tryptic peptides, and cDNA sequencing. The propeptide of WPTP contained N-
      and C-terminal signal sequences which contained 21 and 17 amino acid residues,
      respectively. Mature WPTP was 306 amino acids in length, and its carbohydrate
      content ranged from 21% to 29%. Comparison to closely related royal palm tree
      peroxidase revealed structural features that may explain differences in their
      substrate specificity. The results can be used to guide engineering of WPTP and
      its novel applications. 

PMID- 25383701
TI  - Prospective intraoperative syndesmotic evaluation during ankle fracture fixation:
      stress external rotation versus lateral fibular stress.
AB  - OBJECTIVES: We hypothesized that the method of stress external rotation more
      accurately reproduces the mechanism of injury, and therefore this diagnostic
      method more likely detects ankle instability than the fibular stress examination.
      DESIGN: Prospective cohort comparison study. SETTING: Level 1 trauma center.
      PATIENTS: Twenty-eight consecutive patients with unstable ankle fractures
      presenting within 7 days from the time of injury. Previous ankle surgical history
      or age younger than 18 years was excluded. INTERVENTION: Stress external rotation
      and lateral fibular stress examination was performed intraoperatively. MAIN
      OUTCOME MEASURE: Radiographic measurement of the tibiofibular clear space,
      tibiofibular overlap, and medial clear space were recorded. RESULTS: After
      normalization of the fluoroscopic measurements, there was no difference in
      detecting changes in tibiofibular clear space or tibiofibular overlap. However,
      there was a significant difference in detecting medial clear space widening with
      stress external rotation. Compared with lateral fibular stress, stress external
      rotation demonstrated a 35% increase (P < 0.05) in medial clear space widening.
      This difference correlates with the 1-2-mm difference of additional widening with
      stress external rotation. CONCLUSIONS: Untreated instability impacts patient
      outcomes. The difference in widening with stress external rotation was
      significantly greater than lateral fibular stress and appreciable on standard
      fluoroscopic views. Stress external rotation radiographs are a more reliable
      indicator of mortise instability than traditional lateral fibular stress. LEVEL
      OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25383702
TI  - A single-person reduction and splinting technique for ankle injuries.
AB  - Ankle injuries are one of the most common orthopaedic conditions treated in the
      emergency department. Initial reduction and splinting techniques of these
      injuries are variable and can place undue stress on the physician and cause
      patient discomfort. Novice and experienced practitioners have had to repeat
      splint application because of poor preparation, variable assistant experience,
      loss of fracture reduction, and improper application. We present a modified
      Quigley technique for ankle reduction and splinting that simplifies these issues
      and reduces stress on the patient and physician. The technique was used on 51
      patients without any major complications. This technique can be performed
      entirely by 1 practitioner, by keeping the patient and physician in a comfortable
      position and is applicable to a wide range of lower extremity trauma injuries. 

PMID- 25383703
TI  - Interaction of polycationic Ni(II)-salophen complexes with G-quadruplex DNA.
AB  - A series of nine Ni(II) salophen complexes involving one, two, or three alkyl
      imidazolium side-chains was prepared. The lengths of the side-chains were varied
      from one to three carbons. The crystal structure of one complex revealed a square
      planar geometry of the nickel ion. Fluorescence resonance energy transfer melting
      of G-quadruplex structures in the presence of salophen complex were performed.
      The G-quadruplex DNA structures were stabilized in the presence of the complexes,
      but a duplex DNA was not. The binding constants of the complexes for parallel and
      antiparallel G-quadruplex DNA, as well as hairpin DNA, were measured by surface
      plasmon resonance. The compounds were selective for G-quadruplex DNA, as
      reflected by equilibrium dissociation constant KD values in the region 0.1-1 MUM
      for G-quadruplexes and greater than 2 MUM for duplex DNA. Complexes with more and
      shorter side-chains had the highest binding constants. The structural basis for
      the interaction of the complexes with the human telomeric G-quadruplex DNA was
      investigated by computational studies: the aromatic core of the complex stacked
      over the last tetrad of the G-quadruplex with peripherical cationic side chains
      inserted into opposite grooves. Biochemical studies (telomeric repeat
      amplification protocol assays) indicated that the complexes significantly
      inhibited telomerase activity with IC50 values as low as 700 nM; the complexes
      did not significantly inhibit polymerase activity. 

PMID- 25383704
TI  - Interplay between economic empowerment and sexual behaviour and practices of
      migrant workers within the context of HIV and AIDS in the Lesotho textile
      industry.
AB  - Economic empowerment brings with it a wide range of consequences, both positive
      and negative. The objective of this paper was to examine the relationship between
      economic empowerment and the sexual behaviour and practices of migrant workers
      within the context of HIV and AIDS in the Lesotho textile industry. Data for this
      paper were extracted from the findings of a larger study which had been conducted
      concerning HIV and AIDS in the textile industry in Lesotho. Using in-depth
      interviews, data were collected from 40 participants who were purposively
      selected from five factories which had been chosen randomly. Empowerment theory
      was used as a lens to provide meanings for the experiences of the participants.
      The findings show that the participants were empowered only in certain respects
      in terms of Kabeer's empowerment model of 'power to' and 'power within', on one
      hand, and in terms of Malhotra's comprehensive empowerment framework at the
      household level, on the other, as being employed in the industry enabled them to
      participate in the economy. Employment in the sector provided the participants
      with the means to be able to acquire basic needs and the ability to participate
      in household decision-making: for the female participants, the ability to make
      independent sexual decisions was also enhanced. These improvements were greeted
      enthusiastically, particularly by the female participants, given their previously
      disadvantaged status as a result of coming from rural patriarchal villages with
      gender-defined hegemonic notions of respectability. The findings also indicate
      that environmental factors and others, such as meagre salaries, encouraged some
      of the female workers to engage in transactional sex, while some of the male
      participants tended to increase their sexual relationships as a result of
      acquiring employment and income from the industry. It is the contention of the
      authors of this study that true empowerment requires both vital resources and
      individual and collective participation, particularly for the women, who are more
      vulnerable than men. Finally, we conclude that the opportunities provided by
      economic empowerment have given the participants a new social meaning for their
      situation and an awareness about their place in power relations.

PMID- 25383705
TI  - Helium nanodroplet study of the hydrogen-bonded OH vibrations in HCl-H2O
      clusters.
AB  - Mixed (HCl)N(H2O)M clusters have been assembled in He droplets from the
      constituting molecules. Spectra of the clusters were obtained in the range of
      hydrogen-bonded OH vibrations (3100-3700 cm(-1)) by infrared laser depletion
      spectroscopy. The observed bands were assigned to cyclic hydrogen-bonded
      aggregates containing up to two HCl and three H2O molecules. The obtained
      frequencies are in good agreement with the results of harmonic quantum chemical
      calculations upon appropriate uniform shifts mimicking anharmonic corrections.
      Although larger clusters containing up to six water molecules were also produced
      in the droplets, their spectra were found to contribute to the unresolved signal
      in the range 3250-3550 cm(-1). The fact that no narrow bands could be
      unambiguously assigned to the mixed clusters containing more than three water
      molecules may indicate that such clusters exist in many isomeric forms that lead
      to overlapped and unresolved bands giving rise to broad structureless features.
      Another possible explanation includes the formation of elusive zwitterionic
      clusters, whose bands may have considerable breadth due to electrostatic coupling
      of different vibrational modes and concomitant intramolecular vibrational
      relaxation. 

PMID- 25383706
TI  - Behavioral responses to mammalian blood odor and a blood odor component in four
      species of large carnivores.
AB  - Only little is known about whether single volatile compounds are as efficient in
      eliciting behavioral responses in animals as the whole complex mixture of a
      behaviorally relevant odor. Recent studies analysing the composition of volatiles
      in mammalian blood, an important prey-associated odor stimulus for predators,
      found the odorant trans-4,5-epoxy-(E)-2-decenal to evoke a typical "metallic,
      blood-like" odor quality in humans. We therefore assessed the behavior of captive
      Asian wild dogs (Cuon alpinus), African wild dogs (Lycaon pictus), South American
      bush dogs (Speothos venaticus), and Siberian tigers (Panthera tigris altaica)
      when presented with wooden logs that were impregnated either with mammalian blood
      or with the blood odor component trans-4,5-epoxy-(E)-2-decenal, and compared it
      to their behavior towards a fruity odor (iso-pentyl acetate) and a near-odorless
      solvent (diethyl phthalate) as control. We found that all four species displayed
      significantly more interactions with the odorized wooden logs such as sniffing,
      licking, biting, pawing, and toying, when they were impregnated with the two prey
      associated odors compared to the two non-prey-associated odors. Most importantly,
      no significant differences were found in the number of interactions with the
      wooden logs impregnated with mammalian blood and the blood odor component in any
      of the four species. Only one of the four species, the South American bush dogs,
      displayed a significant decrease in the number of interactions with the odorized
      logs across the five sessions performed per odor stimulus. Taken together, the
      results demonstrate that a single blood odor component can be as efficient in
      eliciting behavioral responses in large carnivores as the odor of real blood,
      suggesting that trans-4,5-epoxy-(E)-2-decenal may be perceived by predators as a
      "character impact compound" of mammalian blood odor. Further, the results suggest
      that odorized wooden logs are a suitable manner of environmental enrichment for
      captive carnivores. 

PMID- 25383707
TI  - Faecal microbiota of forage-fed horses in New Zealand and the population dynamics
      of microbial communities following dietary change.
AB  - The effects of abrupt dietary transition on the faecal microbiota of forage-fed
      horses over a 3-week period were investigated. Yearling Thoroughbred fillies
      reared as a cohort were exclusively fed on either an ensiled conserved forage
      grain diet ("Group A"; n = 6) or pasture ("Group B"; n = 6) for three weeks prior
      to the study. After the Day 0 faecal samples were collected, horses of Group A
      were abruptly transitioned to pasture. Both groups continued to graze similar
      pasture for three weeks, with faecal samples collected at 4-day intervals. DNA
      was isolated from the faeces and microbial 16S and 18S rRNA gene amplicons were
      generated and analysed by pyrosequencing. The faecal bacterial communities of
      both groups of horses were highly diverse (Simpson's index of diversity > 0.8),
      with differences between the two groups on Day 0 (P < 0.017 adjusted for multiple
      comparisons). There were differences between Groups A and B in the relative
      abundances of four genera, BF311 (family Bacteroidaceae; P = 0.003), CF231
      (family Paraprevotellaceae; P = 0.004), and currently unclassified members within
      the order Clostridiales (P = 0.003) and within the family Lachnospiraceae (P =
      0.006). The bacterial community of Group A horses became similar to Group B
      within four days of feeding on pasture, whereas the structure of the archaeal
      community remained constant pre- and post-dietary change. The community structure
      of the faecal microbiota (bacteria, archaea and ciliate protozoa) of pasture-fed
      horses was also identified. The initial differences observed appeared to be
      linked to recent dietary history, with the bacterial community of the forage-fed
      horses responding rapidly to abrupt dietary change.

PMID- 25383708
TI  - Chloride-induced morphology transformations of the Cu(110) surface in dilute HCl.
AB  - Morphological changes of a bare Cu(110) substrate in 10 mM HCl aqueous solution
      have been studied using cyclic voltammetry (CV), electrochemical scanning
      tunneling microscopy (EC-STM), and reflectance anisotropy spectroscopy (RAS). At
      cathodic potentials more positive than the hydrogen evolution reaction, a bare
      copper surface (1 * 1) structure is found by EC-STM. At anodic potentials more
      negative than the copper(II) dissolution reaction, a furrowed structure is found.
      The governing factor that rules Cu(110)-Cl interface processes is discussed as an
      interplay among Cl(-) adsorption/desorption, the dynamic rearrangement of the
      surface atoms on the substrate, and strain in order to reduce the surface energy.
      The information provided by EC-STM and RAS complements that of CV, supplies
      detailed information on the surface morphology, and correlates peaking Faraday
      currents to structural modifications. Furthermore, RAS and EC-STM show changes in
      the surface appearance in a potential range where no specific charge transfer is
      observed. CV indicates that the Cu(110) surface chemistry compares much better to
      that of amorphous Cu than to that of the more stable (100) and (111) surfaces,
      respectively. 

PMID- 25383709
TI  - Measuring and modeling the effect of surface moisture on the spectral reflectance
      of coastal beach sand.
AB  - Surface moisture is an important supply limiting factor for aeolian sand
      transport, which is the primary driver of coastal dune development. As such, it
      is critical to account for the control of surface moisture on available sand for
      dune building. Optical remote sensing has the potential to measure surface
      moisture at a high spatio-temporal resolution. It is based on the principle that
      wet sand appears darker than dry sand: it is less reflective. The goals of this
      study are (1) to measure and model reflectance under controlled laboratory
      conditions as function of wavelength (lambda) and surface moisture (theta) over
      the optical domain of 350-2500 nm, and (2) to explore the implications of our
      laboratory findings for accurately mapping the distribution of surface moisture
      under natural conditions. A laboratory spectroscopy experiment was conducted to
      measure spectral reflectance (1 nm interval) under different surface moisture
      conditions using beach sand. A non-linear increase of reflectance upon drying was
      observed over the full range of wavelengths. Two models were developed and
      tested. The first model is grounded in optics and describes the proportional
      contribution of scattering and absorption of light by pore water in an
      unsaturated sand matrix. The second model is grounded in soil physics and links
      the hydraulic behaviour of pore water in an unsaturated sand matrix to its
      optical properties. The optical model performed well for volumetric moisture
      content theta < 24% (R2 > 0.97), but underestimated reflectance for theta between
      24-30% (R2 > 0.92), most notable around the 1940 nm water absorption peak. The
      soil-physical model performed very well (R2 > 0.99) but is limited to 4% > theta
      < 24%. Results from a field experiment show that a short-wave infrared
      terrestrial laser scanner (lambda = 1550 nm) can accurately relate surface
      moisture to reflectance (standard error 2.6%), demonstrating its potential to
      derive spatially extensive surface moisture maps of a natural coastal beach.

PMID- 25383710
TI  - HIV laboratory monitoring reliably identifies persons engaged in care.
AB  - BACKGROUND: Attendance at biannual medical encounters has been proposed as a
      minimum national standard for adequate engagement in HIV care. Using data from
      the HIV Outpatient Study, we analyzed how well dates of HIV-related laboratory
      testing correlated with attendance at biannual medical encounters. METHODS: HIV
      Outpatient Study is an open prospective cohort study of HIV-infected patients
      receiving outpatient care in the United States. The data set included dates for
      laboratory measurements and medical encounters. We included patients with at
      least 1 HIV laboratory test (CD4 cell count or plasma HIV RNA viral load) during
      2010-2011. An HIV laboratory test was defined as associated with a medical
      encounter if it occurred within 3 weeks of the encounter. We assessed the
      predictive value of HIV laboratory tests as a proxy for adequate engagement in
      clinical care, defined as having had >=2 HIV laboratory tests within 1 year and
      performed >90 days apart. RESULTS: A total of 10,321 HIV laboratory tests were
      recorded from 2909 patients. Adequate engagement in clinical care based on
      medical encounters was 88.2% and 77.3% when based on laboratory tests. Using HIV
      laboratory tests to assess engagement had a sensitivity of 85.7%, specificity of
      86.0%, and positive and negative predictive values of 97.9% and 44.5%,
      respectively. Of the 22.7% classified as not engaged in care by the proxy
      measure, over half (55.5%) were actually engaged. CONCLUSIONS: Using laboratory
      monitoring reliably classified persons as engaged in care. Of the 22.7% of
      patients classified as not engaged in care, most were actually engaged.

PMID- 25383711
TI  - On the prospect of identifying adaptive loci in recently bottlenecked
      populations.
AB  - Identifying adaptively important loci in recently bottlenecked populations - be
      it natural selection acting on a population following the colonization of novel
      habitats in the wild, or artificial selection during the domestication of a breed
      - remains a major challenge. Here we report the results of a simulation study
      examining the performance of available population-genetic tools for identifying
      genomic regions under selection. To illustrate our findings, we examined the
      interplay between selection and demography in two species of Peromyscus mice, for
      which we have independent evidence of selection acting on phenotype as well as
      functional evidence identifying the underlying genotype. With this unusual
      information, we tested whether population-genetic-based approaches could have
      been utilized to identify the adaptive locus. Contrary to published claims, we
      conclude that the use of the background site frequency spectrum as a null model
      is largely ineffective in bottlenecked populations. Results are quantified both
      for site frequency spectrum and linkage disequilibrium-based predictions, and are
      found to hold true across a large parameter space that encompasses many species
      and populations currently under study. These results suggest that the genomic
      footprint left by selection on both new and standing variation in strongly
      bottlenecked populations will be difficult, if not impossible, to find using
      current approaches. 

PMID- 25383713
TI  - Postgraduate education in psychiatric nursing in Israel: closing the gap.
AB  - Deinstitutionalization policies are being gradually implemented in Israel. Most
      recently, an insurance reform has been approved, in which mental health services
      will be included in the HMO's service package. As most Israeli mental health
      nurses are currently employed in institutional settings, the Ministry of Health's
      Nursing Division seeks to estimate their scope of employment in preparation for
      the anticipated changes. The aim of this study is to describe present-day
      professional practice characteristics of qualified psychiatric nurses and
      identify practice areas for which advanced training may be required. The research
      design is cross-sectional on a national level, including all state psychiatric
      hospitalization services. A countrywide sample of nurses with post-basic training
      in state psychiatric hospitals identified areas of practice in which further
      training may be required: psychotherapy intervention (60% of respondents);
      consultation for the elderly (60%); care prescriptions (64%); community drug
      treatment management (69%); and referral to professionals and community resources
      (56%). Nurses reported gaps in continued care and community rehabilitation
      activities. These findings have training implications in an era of increased
      focus on chronic mental illness in the community. 

PMID- 25383712
TI  - Evidence for SH2 domain-containing 5'-inositol phosphatase-2 (SHIP2) contributing
      to a lymphatic dysfunction.
AB  - The lymphatic vasculature plays a critical role in a number of disease conditions
      of increasing prevalence, such as autoimmune disorders, obesity, blood vascular
      diseases, and cancer metastases. Yet, unlike the blood vasculature, the tools
      available to interrogate the molecular basis of lymphatic dysfunction/disease
      have been lacking. More recently, investigators have reported that dysregulation
      of the PI3K pathway is involved in syndromic human diseases that involve abnormal
      lymphatic vasculatures, but there have been few compelling results that show the
      direct association of this molecular pathway with lymphatic dysfunction in
      humans. Using near-infrared fluorescence lymphatic imaging (NIRFLI) to phenotype
      and next generation sequencing (NGS) for unbiased genetic discovery in a family
      with non-syndromic lymphatic disease, we discovered a rare, novel mutation in
      INPPL1 that encodes the protein SHIP2, which is a negative regulator of the PI3K
      pathway, to be associated with lymphatic dysfunction in the family. In vitro
      interrogation shows that SHIP2 is directly associated with impairment of normal
      lymphatic endothelial cell (LEC) behavior and that SHIP2 associates with
      receptors that are associated in lymphedema, implicating its direct involvement
      in the lymphatic vasculature. 

PMID- 25383714
TI  - A physiologically-motivated compartment-based model of the effect of inhaled
      hypertonic saline on mucociliary clearance and liquid transport in cystic
      fibrosis.
AB  - BACKGROUND: Cystic Fibrosis (CF) lung disease is characterized by liquid
      hyperabsorption, airway surface dehydration, and impaired mucociliary clearance
      (MCC). Herein, we present a compartment-based mathematical model of the airway
      that extends the resolution of functional imaging data. METHODS: Using functional
      imaging data to inform our model, we developed a system of mechanism-motivated
      ordinary differential equations to describe the mucociliary clearance and
      absorption of aerosolized radiolabeled particle and small molecules probes from
      human subjects with and without CF. We also utilized a novel imaging metric in
      vitro to gauge the fraction of airway epithelial cells that have functional
      ciliary activity. RESULTS: This model, and its incorporated kinetic rate
      parameters, captures the MCC and liquid dynamics of the hyperabsorptive state in
      CF airways and the mitigation of that state by hypertonic saline treatment.
      CONCLUSIONS: We postulate, based on the model structure and its ability to
      capture clinical patient data, that patients with CF have regions of airway with
      diminished MCC function that can be recruited with hypertonic saline treatment.
      In so doing, this model structure not only makes a case for durable osmotic
      agents used in lung-region specific treatments, but also may provide a possible
      clinical endpoint, the fraction of functional ciliated airway.

PMID- 25383715
TI  - Palm-vein classification based on principal orientation features.
AB  - Personal recognition using palm-vein patterns has emerged as a promising
      alternative for human recognition because of its uniqueness, stability, live body
      identification, flexibility, and difficulty to cheat. With the expanding
      application of palm-vein pattern recognition, the corresponding growth of the
      database has resulted in a long response time. To shorten the response time of
      identification, this paper proposes a simple and useful classification for palm
      vein identification based on principal direction features. In the registration
      process, the Gaussian-Radon transform is adopted to extract the orientation
      matrix and then compute the principal direction of a palm-vein image based on the
      orientation matrix. The database can be classified into six bins based on the
      value of the principal direction. In the identification process, the principal
      direction of the test sample is first extracted to ascertain the corresponding
      bin. One-by-one matching with the training samples is then performed in the bin.
      To improve recognition efficiency while maintaining better recognition accuracy,
      two neighborhood bins of the corresponding bin are continuously searched to
      identify the input palm-vein image. Evaluation experiments are conducted on three
      different databases, namely, PolyU, CASIA, and the database of this study.
      Experimental results show that the searching range of one test sample in PolyU,
      CASIA and our database by the proposed method for palm-vein identification can be
      reduced to 14.29%, 14.50%, and 14.28%, with retrieval accuracy of 96.67%, 96.00%,
      and 97.71%, respectively. With 10,000 training samples in the database, the
      execution time of the identification process by the traditional method is 18.56
      s, while that by the proposed approach is 3.16 s. The experimental results
      confirm that the proposed approach is more efficient than the traditional method,
      especially for a large database. 

PMID- 25383716
TI  - Chronic biofilm infection in breast implants is associated with an increased T
      cell lymphocytic infiltrate: implications for breast implant-associated lymphoma.
AB  - BACKGROUND: Biofilm infection of breast implants significantly potentiates
      capsular contracture. This study investigated whether chronic biofilm infection
      could promote T-cell hyperplasia. METHODS: In the pig study, 12 textured and 12
      smooth implants were inserted into three adult pigs. Implants were left in situ
      for a mean period of 8.75 months. In the human study, 57 capsules from patients
      with Baker grade IV contracture were collected prospectively over a 4-year
      period. Biofilm and surrounding lymphocytes were analyzed using culture, nucleic
      acid, and visualization techniques. RESULTS: In the pig study, all samples were
      positive for bacterial biofilm. There was a significant correlation between the
      bacterial numbers and grade of capsular contracture (p = 0.04). Quantitative real
      time polymerase chain reaction showed that all lymphocytes were significantly
      more numerous on textured compared with smooth implants (p < 0.001). T cells
      accounted for the majority of the lymphocytic infiltrate. Imaging confirmed the
      presence of activated lymphocytes. In the human study, all capsules were positive
      for biofilm. Analysis of lymphocyte numbers showed a T-cell predominance (p <
      0.001). There was a significant linear correlation between the number of T and B
      cells and the number of detected bacteria (p < 0.001). Subset analysis showed a
      significantly higher number of bacteria for polyurethane implants (p < 0.005).
      CONCLUSIONS: Chronic biofilm infection around breast prostheses produces an
      increased T-cell response both in the pig and in humans. A possible link between
      bacterial biofilm and T-cell hyperplasia is significant in light of breast
      implant-associated anaplastic large-cell lymphoma. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Risk, V.

PMID- 25383717
TI  - Hand hygiene knowledge and perceptions among anesthesia providers.
AB  - BACKGROUND: Health care worker compliance with hand hygiene guidelines is an
      important measure for health care-associated infection prevention, yet overall
      compliance across all health care arenas remains low. A correct answer to 4 of 4
      structured questions pertaining to indications for hand decontamination
      (according to types of contact) has been associated with improved health care
      provider hand hygiene compliance when compared to those health care providers
      answering incorrectly for 1 or more questions. A better understanding of
      knowledge deficits among anesthesia providers may lead to hand hygiene
      improvement strategies. In this study, our primary aims were to characterize and
      identify predictors for hand hygiene knowledge deficits among anesthesia
      providers. METHODS: We modified this previously tested survey instrument to
      measure anesthesia provider hand hygiene knowledge regarding the 5 moments of
      hand hygiene across national and multicenter groups. Complete knowledge was
      defined by correct answers to 5 questions addressing the 5 moments for hand
      hygiene and received a score of 1. Incomplete knowledge was defined by an
      incorrect answer to 1 or more of the 5 questions and received a score of 0. We
      used a multilevel random-effects XTMELOGIT logistic model clustering at the
      respondent and geographic location for insufficient knowledge and
      forward/backward stepwise logistic regression analysis to identify predictors for
      incomplete knowledge. RESULTS: The survey response rates were 55.8% and 18.2% for
      the multicenter and national survey study groups, respectively. One or more
      knowledge deficits occurred with 81.6% of survey respondents, with the mean
      number of correct answers 2.89 (95% confidence interval, 2.78- 2.99). Failure of
      providers to recognize prior contact with the environment and prior contact with
      the patient as hand hygiene opportunities contributed to the low mean. Several
      cognitive factors were associated with a reduced risk of incomplete knowledge
      including providers responding positively to washing their hands after contact
      with the environment (odds ratio [OR] 0.23, 0.14-0.37, P < 0.001), disinfecting
      their environment during patient care (OR 0.54, 0.35-0.82, P = 0.004), believing
      that they can influence their colleagues (OR 0.43, 0.27-0.68, P < 0.001), and
      intending to adhere to guidelines (OR 0.56, 0.36-0.86, P = 0.008). These
      covariates were associated with an area under receiver operator characteristics
      curve of 0.79 (95% confidence interval, 0.74-0.83). CONCLUSIONS: Anesthesia
      provider knowledge deficits around to hand hygiene guidelines occur frequently
      and are often due to failure to recognize opportunities for hand hygiene after
      prior contact with contaminated patient and environmental reservoirs.
      Intraoperative hand hygiene improvement programs should address these knowledge
      deficits. Predictors for incomplete knowledge as identified in this study should
      be validated in future studies.

PMID- 25383718
TI  - Isoflurane protects the myocardium against ischemic injury via the preservation
      of mitochondrial respiration and its supramolecular organization.
AB  - BACKGROUND: Isoflurane has been demonstrated to limit myocardial ischemic injury.
      This effect is hypothesized to be mediated in part via effects on mitochondria.
      We investigated the hypothesis that isoflurane maintains mitochondrial
      respiratory chain functionality, in turn limiting mitochondrial damage and
      mitochondrial membrane disintegration during myocardial ischemic injury. METHODS:
      Mice (9-12 weeks of age) received isoflurane (1.0 minimum alveolar concentration)
      36 hours before a 30-minute coronary artery occlusion that was followed by 24
      hours of reperfusion. Cardiac mitochondria were isolated at a time point
      corresponding to 4 hours of reperfusion. 2,3,5-Triphenyltetrazoliumchloride
      staining was used to determine myocardial infarct size. Mitochondrial respiratory
      chain functionality was investigated using blue native polyacrylamide gel
      electrophoresis, as well as specific biochemical assays. Mitochondrial lipid
      peroxidation was quantified via the formation of malondialdehyde; mitochondrial
      membrane integrity was assessed by Ca-induced swelling. Protein identification
      was achieved via liquid chromatography mass spectrometry/mass spectrometry.
      RESULTS: Thirty-one mice were studied. Mice receiving isoflurane displayed a
      reduced myocardial infarct size (P = 0.0011 versus ischemia/reperfusion [I/R]),
      accompanied by a preserved activity of respiratory complex III (P = 0.0008 versus
      I/R). Isoflurane stabilized mitochondrial supercomplexes consisting of oligomers
      from complex III/IV (P = 0.0086 versus I/R). Alleviation of mitochondrial damage
      after isoflurane treatment was further demonstrated as decreased malondialdehyde
      formation (P = 0.0019 versus I/R) as well as a diminished susceptibility to Ca
      induced swelling (P = 0.0010 versus I/R). CONCLUSIONS: Our findings support the
      hypothesis that isoflurane protects the heart from ischemic injury by maintaining
      the in vivo functionality of the mitochondrial respiratory chain. These effects
      may result in part from the preservation of mitochondrial supramolecular
      organization and minimized oxidative damage, circumventing the loss of
      mitochondrial membrane integrity.

PMID- 25383720
TI  - Controversies in ASSAY and drug development technologies: a focus on assessing
      irreproducibility.
AB  - Has the impact of irreproducibility on the discovery and development of drugs, as
      with global warming, metaphorically speaking, crept up on us as we slept? Or is
      the problem more an issue of heightened awareness? We currently find ourselves in
      a time when the impact of irreproducibility can easily be amplified by the
      combinatorial effect of our increasing reliance on advanced technologies and
      unrealistic expectations of how scientific truths unfold. How and why we got here
      is a topic that has been written on extensively (1-3) and is probably as complex
      as any other problem, given the dependence of science today on so many external
      forces. Through a series of questions, we asked members of our editorial board
      their opinions on scientific irreproducibility. They chose to answer the same
      questions from different levels, indicating the depth of the problem and perhaps
      where they each believe change for the better needs to begin. My thanks to the
      participants.

PMID- 25383719
TI  - Psychological sequelae of surgery in a prospective cohort of patients from three
      intraoperative awareness prevention trials.
AB  - BACKGROUND: Elective surgery can have long-term psychological sequelae,
      especially for patients who experience intraoperative awareness. However, risk
      factors, other than awareness, for symptoms of posttraumatic stress disorder
      (PTSD) after surgery are poorly defined, and practical screening methods have not
      been applied to a broad population of surgical patients. METHODS: The
      Psychological Sequelae of Surgery study was a prospective cohort study of
      patients previously enrolled in the United States and Canada in 3 trials for the
      prevention of intraoperative awareness. The 68 patients who experienced definite
      or possible awareness were matched with 418 patients who denied awareness based
      on age, sex, surgery type, and awareness risk. Participants completed the PTSD
      Checklist-Specific (PCL-S) and/or a modified Mini-International Neuropsychiatric
      Interview telephone assessment to identify symptoms of PTSD and symptom complexes
      consistent with a PTSD diagnosis. We then used structural equation modeling to
      produce a composite PTSD score and examined potential risk factors. RESULTS: One
      hundred forty patients were unreachable; of those contacted, 303 (88%)
      participated a median of 2 years postoperatively. Forty-four of the 219 patients
      (20.1%) who completed the PCL-S exceeded the civilian screening cutoff score for
      PTSD symptoms resulting from their surgery (15 of 35 [43%] with awareness and 29
      of 184 [16%] without). Nineteen patients (8.7%; 5 of 35 [14%] with awareness and
      14 of 184 [7.6%] without) both exceeded the cutoff and endorsed a breadth of
      symptoms consistent with the Diagnostic and Statistical Manual Fourth Edition
      diagnosis of PTSD attributable to their surgery. Factors independently associated
      with PTSD symptoms were poor social support, previous PTSD symptoms, previous
      mental health treatment, dissociation related to surgery, perceiving that one's
      life was threatened during surgery, and intraoperative awareness (all P <=
      0.017). Perioperative dissociation was identified as a potential mediator for
      perioperative PTSD symptoms. CONCLUSIONS: Events in the perioperative period can
      precipitate psychological symptoms consistent with subsyndromal and syndromal
      PTSD. We not only confirmed the high rate of postoperative PTSD in awareness
      patients but also identified a significant rate in matched nonawareness controls.
      Screening surgical patients, especially those with potentially mediating risk
      factors such as intraoperative awareness or perioperative dissociation, for
      postoperative PTSD symptoms with the PCL-S is practical and could promote early
      referral, evaluation, and treatment.

PMID- 25383721
TI  - High-throughput screening for small molecule modulators of motor protein Kinesin.
AB  - The kinesin superfamily of motor proteins are involved in the active transport of
      a large number of cargos such as organelles, proteins, and RNAs from the neuronal
      cell body to distal neuronal processes. Previously, we have shown that kinesin
      mediated axonal transport of proteins and RNAs are important for long-term memory
      storage. Identification of small molecules that can activate or inhibit kinesins
      is of specific interest due to the significance of kinesin-mediated functions in
      neuronal health and plasticity. Here, we describe a high-throughput screening
      assay designed to specifically identify compounds that inhibit or activate
      adenosine triphosphatase activity of the kinesin 5B of humans. The luminescence
      based assay that we developed is highly reproducible and robust. Using this
      approach, we screened a pharmacologically characterized compound collection and
      have identified small molecules with either activator or inhibitor-like activity.
      To further characterize screening hits, we also developed an orthogonal assay
      based on absorbance and a counter screen assay based on luminescence. Development
      of such assays is important to help identify small molecules that can be used in
      potential drug development efforts targeted at modulating the function of
      kinesin.

PMID- 25383723
TI  - On physiological demands and sustainability in meat cutting.
AB  - Meat cutters' work has been investigated by several researchers. However,
      knowledge about the physiological demands of meat cutting is almost lacking. The
      aim of this explorative study was to assess physiological demands in meat
      cutting, to compare them with International Labour Organization (ILO)
      recommendations for acceptable workload and to discuss the findings in relation
      to individual and work-related factors. In accordance with the ILO
      recommendations, work was categorised as sustainable or non-sustainable based on
      critical relative aerobic strain (RAS) levels. Twenty-one beef and pork cutters
      participated in the study, which included workload measurements, assessment of
      workplace and individual factors. Thirteen meat cutters were categorised as
      having non-sustainable and eight as having sustainable work. Results suggest that
      the workload is higher in beef cutting than in pork cutting, and that longer work
      experience is related to lower RAS. Other factors contributing to the physical
      workload are discussed. PRACTITIONER SUMMARY: Meat-cutting work may exceed
      recommended physical workload levels. Beef cutting is physically more demanding
      than pork cutting. Furthermore, factors such as years in the profession, knife
      sharpness, work pace, wage system, working technique, maximum oxygen uptake level
      and muscular strength should be considered when planning actions regarding the
      workload for meat cutters.

PMID- 25383722
TI  - Development and validation of a robust and sensitive assay for the discovery of
      selective inhibitors for serine/threonine protein phosphatases PP1alpha (PPP1C)
      and PP5 (PPP5C).
AB  - Protein phosphatase types 1 alpha (PP1alpha/PPP1C) and 5 (PP5/PPP5C) are members
      of the PPP family of serine/threonine protein phosphatases. PP1 and PP5 share a
      common catalytic mechanism, and several natural compounds, including okadaic
      acid, microcystin, and cantharidin, act as strong inhibitors of both enzymes.
      However, to date there have been no reports of compounds that can selectively
      inhibit PP1 or PP5, and specific or highly selective inhibitors for either PP1 or
      PP5 are greatly desired by both the research and pharmaceutical communities. Here
      we describe the development and optimization of a sensitive and robust
      (representative PP5C assay data: Z'=0.93; representative PP1Calpha assay data:
      Z'=0.90) fluorescent phosphatase assay that can be used to simultaneously screen
      chemical libraries and natural product extracts for the presence of catalytic
      inhibitors of PP1 and PP5.

PMID- 25383725
TI  - Core self-evaluations and well-being in persons with disabilities.
AB  - PURPOSE: The purpose of this article is to introduce the concept of core self
      evaluations (CSE), which is conceptualized as the overall, fundamental perception
      that individuals have about their worth and capability as people (Judge, Locke,
      Durham, & Kluger, 1998). CSE is a higher order variable that is reflective of the
      self-concept and comprises personality traits including self-esteem, generalized
      self-efficacy, locus of control, and emotional stability. METHOD: In this
      article, the theoretical background of the CSE construct is reviewed, the
      existing literature on CSE in the general population is summarized, and future
      directions for the use of CSE in rehabilitation psychology research and clinical
      settings is proposed. IMPLICATIONS: CSE has great potential as a global positive
      contributor of well-being in persons with disabilities, and research addressing
      its relationship with outcomes such as well-being and its clinical applications
      has great promise to augment rehabilitation psychology practice in the future.

PMID- 25383724
TI  - The impact of the modified Atkins diet on lipid profiles in adults with epilepsy.
AB  - OBJECTIVES: The modified Atkins diet (MAD) is a high fat, low carbohydrate
      ketogenic diet used to treat intractable seizures in children and adults. The
      long-term impact on fasting lipid profiles (FLPs) remains unknown. This study was
      designed to detect significant lipid changes in adults on MAD. METHODS: Patients
      were observed prospectively. A FLP was obtained in all patients at the first
      visit then serially. Patients were started on a 20 g per day net carbohydrate
      limit MAD. They were screened for risk for coronary heart disease and counseled
      to reduce saturated fats by a registered dietitian if deemed at risk. Patients
      that remained on MAD for 3 or more months with one or more follow-up FLP were
      included. RESULTS: Thirty-seven patients (14 male), mean age 33 years (SD 13,
      range 18-59) met study criteria. Median diet duration was 16 months (range 3-41).
      Total cholesterol and low-density lipoprotein (LDL) increased significantly over
      the first 3 months of MAD (P = 0.01 and 0.008, respectively), but were not
      significantly different from baseline after 1 year of treatment (P = 0.2 and P =
      0.5, respectively). High-density lipoprotein levels trended upward in the first 3
      months (P = 0.05) and triglycerides remained unchanged (P = 0.5). In 12 patients
      followed for 3 or more years, no cardiovascular or cerebrovascular events were
      reported. DISCUSSION: Although total cholesterol and LDL increased over the first
      3 months of the MAD, these values normalized within a year of treatment,
      including in patients treated with MAD for more than 3 years.

PMID- 25383726
TI  - Perimenopausal bleeding: Patterns, pathology, response to progestins and clinical
      outcome.
AB  - This prospective observational study was done on 400 perimenopausal patients who
      presented with abnormal uterine bleeding with selective endometrial lesions
      diagnosed on histopathology. Patients were followed to determine their response
      to progestin therapy and their final clinical outcome. The commonest bleeding
      pattern was menorrhagia (67.5%), the commonest pathology was simple endometrial
      hyperplasia without atypia (31%). 142 cases with non- atypical endometrial
      hyperplasia received progestin therapy with follow up, 100 cases (70.4%)
      experienced lesion regression, 38 cases (26.7%) experienced persistence and four
      cases (2.9%) experienced progression to atypia. Low dose progestin therapy (< 20
      mg/day) was more effective when used for 4-5 months. Hysterectomy was done for 44
      cases, due to atypical endometrial hyperplasia, persistence and progression of
      non atypical hyperplasia. Perimenopausal bleeding is mostly dysfunctional in
      origin but organic lesions remained a major concern which requires endometrial
      sampling with proper interpretation to achieve better clinical outcome. 

PMID- 25383727
TI  - Brachial-ankle pulse wave velocity and mean platelet volume as predictive values
      after percutaneous coronary intervention for long-term clinical outcomes in
      Korea: A comparable and additive study.
AB  - This study aimed to determine the association of the brachial-ankle pulse wave
      velocity (baPWV) and mean platelet volume (MPV) with the development of adverse
      outcomes after percutaneous coronary intervention (PCI). The baPWV and MPV were
      analyzed in 372 patients who underwent PCI, with the primary endpoint as cardiac
      death. The secondary endpoint was cardiovascular events (CVE): a composite of
      cardiac death, myocardial infarction (MI), target vessel revascularization (TVR),
      ischemic stroke, and stent thrombosis (ST). During the follow-up period (mean,
      25.8 months), there were 21 cardiac deaths, 10 MIs including four events of ST,
      seven ischemic strokes, and 29 TVRs. The baPWV cut-off level was set at 1672 cm/s
      using the receiver operating characteristic curve; the sensitivity and
      specificity was 85.7 and 60.1%, respectively, to differentiate between the groups
      with and without cardiac death. The MPV cut-off level was set at 8.20 fL using
      the receiver operating characteristic curve; the sensitivity and specificity were
      81 and 53.3%, respectively, to differentiate between the groups with and without
      cardiac death. Kaplan-Meier analysis revealed that the higher baPWV group (>=
      1672 cm/s) had a significantly higher cardiac death and CVE rate than the lower
      baPWV group (<1672 cm/s) (11.4 vs. 1.4%, log-rank: p < 0.0001; 25.3 vs. 7.5%, log
      rank: p < 0.0001; respectively), and the higher MPV group (median, >8.20 fL,) had
      a significantly higher cardiac death and CVE rate than the lower MPV group (<=
      8.20 fL) (9.4 vs. 2.1%, log-rank: p = 0.0026; 23.8 vs. 6.8%, log-rank: p <
      0.0001; respectively). Furthermore, the high baPWV and MPV groups were
      significantly associated with an increased risk of cardiac death. These results
      show that baPWV and MPV are predictive markers after PCI for cardiac death; they
      are also additively associated with a higher risk of cardiac death.

PMID- 25383728
TI  - Thyroid surgery and the usefulness of intraoperative neuromonitoring, a single
      center study.
AB  - Purpose/Aim of study: To compare the use of intraoperative neuromonitoring (IONM)
      versus visualization of the recurrent laryngeal nerve (RLN) alone in thyroid
      surgery with regard to incidence in postoperative RLN injury and operation time.
      MATERIALS AND METHODS: This retrospective cohort study was performed in the
      Amphia Hospital, the Netherlands. All thyroid gland operations were collected
      from September 2009 to October 2012. For each case we recorded the patient
      characteristics, indication for surgery, intraoperative data, complications,
      results of pathological evaluation, and consultation of a ENT-surgeon. Research
      of current literature and statistical analysis was performed. RESULTS: In total,
      147 patients were included and classified into an IONM and non-IONM group. Both
      groups were similar in demographical aspects and indications for surgery. In
      total, we had 170 nerves at risk (NAR). In both groups, there were 85 (50%) NAR.
      Overall injury to the RLN was 6%. A statistical significant decrease of permanent
      RLN injuries was noticed in the IONM group compared to the non-IONM group (n = 0
      vs n = 6; p = .044). In transient RLN injury, no difference was noticed (n = 2 vs
      n = 2). Operation time with or without IONM was not significantly different for
      hemithyroidectomies, neither for total thyroidectomies. CONCLUSION: IONM is a
      useful tool as an adjunct in thyroid surgery to prevent RLN injury. A statistical
      significant decrease in permanent RLN injury with the use of IONM was found, but
      it did not significantly decrease time of operation.

PMID- 25383729
TI  - Fast motion-including dose error reconstruction for VMAT with and without MLC
      tracking.
AB  - Multileaf collimator (MLC) tracking is a promising and clinically emerging
      treatment modality for radiotherapy of mobile tumours. Still, new quality
      assurance (QA) methods are warranted to safely introduce MLC tracking in the
      clinic. The purpose of this study was to create and experimentally validate a
      simple model for fast motion-including dose error reconstruction applicable to
      intrafractional QA of MLC tracking treatments of moving targets.MLC tracking
      experiments were performed on a standard linear accelerator with prototype MLC
      tracking software guided by an electromagnetic transponder system. A three-axis
      motion stage reproduced eight representative tumour trajectories; four lung and
      four prostate. Low and high modulation 6 MV single-arc volumetric modulated arc
      therapy treatment plans were delivered for each trajectory with and without MLC
      tracking, as well as without motion for reference. Temporally resolved doses were
      measured during all treatments using a biplanar dosimeter. Offline, the dose
      delivered to each of 1069 diodes in the dosimeter was reconstructed with 500 ms
      temporal resolution by a motion-including pencil beam convolution algorithm
      developed in-house. The accuracy of the algorithm for reconstruction of dose and
      motion-induced dose errors throughout the tracking and non-tracking beam
      deliveries was quantified. Doses were reconstructed with a mean dose difference
      relative to the measurements of-0.5% (5.5% standard deviation) for cumulative
      dose. More importantly, the root-mean-square deviation between reconstructed and
      measured motion-induced 3%/3 mm gamma failure rates (dose error) was 2.6%. The
      mean computation time for each calculation of dose and dose error was 295 ms. The
      motion-including dose reconstruction allows accurate temporal and spatial
      pinpointing of errors in absorbed dose and is adequately fast to be feasible for
      online use. An online implementation could allow treatment intervention in case
      of erroneous dose delivery in both tracking and non-tracking treatments.

PMID- 25383730
TI  - Forensic and clinical toxicology.

PMID- 25383731
TI  - Nails: an adequate alternative matrix in forensic toxicology for drug analysis?

PMID- 25383732
TI  - Trends in drug testing in oral fluid and hair as alternative matrices.
AB  - The use of alternative matrices such as oral fluid and hair has increased in the
      past decades because of advances in analytical technology. However, there are
      still many issues that need to be resolved. Standardized protocols of sample
      pretreatment are needed to link the detected concentrations to final conclusions.
      The development of suitable proficiency testing schemes is required. Finally,
      interpretation issues such as link to effect, adulteration, detection markers and
      thresholds will hamper the vast use of these matrices. Today, several niche areas
      apply these matrices with success, such as drugs and driving for oral fluid and
      drug-facilitated crimes for hair. Once those issues are resolved, the number of
      applications will markedly grow in the future. 

PMID- 25383733
TI  - Spot them in the spot: analysis of abused substances using dried blood spots.
AB  - Dried blood spot (DBS) sampling and DBS analysis have increasingly received
      attention during recent years. Furthermore, a substantial number of DBS methods
      has recently become available in clinical, forensic and occupational toxicology.
      In this review, we provide an overview of the different DBS-based methods that
      have been developed for detecting (markers of) abused substances. These include
      both legal and illegal drugs belonging to different categories, including
      cannabinoids, cocaine and metabolites, opioids, benzodiazepines and Z-drugs,
      amphetamines and analogs, gamma-hydroxybutyric acid, ketamine and novel
      psychoactive substances such as cathinones. Markers of ethanol consumption and
      tobacco use are also covered in this review. Since the majority of published
      methods has shown promising results overall, an interesting role for DBS analysis
      in diverse toxicological applications can be envisaged. For the distinct
      applications, we discuss the specific potential and benefits of DBS, the
      associated limitations and challenges, as well as recent developments and future
      perspectives.

PMID- 25383734
TI  - Methods for urine drug testing using one-step dilution and direct injection in
      combination with LC-MS/MS and LC-HRMS.
AB  - The advent of LC combined with MS made it possible to design analytical methods
      for urine drug testing based on the very simple concept of diluting urine with an
      internal standard as the sole preparation procedure prior to instrumental
      analysis. The number of publications using this method design increased after the
      development of high-efficiency LC based on sub-2 MUm particles. The success of
      this method design for drug testing, doping control and toxicological
      investigations of urine is now well documented and comprise both screening and
      confirmation methods. The nondiscriminating nature of this method design makes it
      even more attractive in combination with high-resolution MS for multicomponent
      target and general unknown analysis applications. 

PMID- 25383735
TI  - Current role of ICP-MS in clinical toxicology and forensic toxicology: a metallic
      profile.
AB  - As metal/metalloid exposure is inevitable owing to its omnipresence, it may exert
      toxicity in humans. Recent advances in metal/metalloid analysis have been made
      moving from flame atomic absorption spectrometry and electrothermal atomic
      absorption spectrometry to the multi-elemental inductively coupled plasma (ICP)
      techniques as ICP atomic emission spectrometry and ICP-MS. ICP-MS has now emerged
      as a major technique in inorganic analytical chemistry owing to its flexibility,
      high sensitivity and good reproducibility. This in depth review explores the ICP
      MS metallic profile in human toxicology. It is now routinely used and of great
      importance, in clinical toxicology and forensic toxicology to explore biological
      matrices, specifically whole blood, plasma, urine, hair, nail, biopsy samples and
      tissues. 

PMID- 25383736
TI  - The current role of on-line extraction approaches in clinical and forensic
      toxicology.
AB  - In today's clinical and forensic toxicological laboratories, automation is of
      interest because of its ability to optimize processes, to reduce manual workload
      and handling errors and to minimize exposition to potentially infectious samples.
      Extraction is usually the most time-consuming step; therefore, automation of this
      step is reasonable. Currently, from the field of clinical and forensic
      toxicology, methods using the following on-line extraction techniques have been
      published: on-line solid-phase extraction, turbulent flow chromatography, solid
      phase microextraction, microextraction by packed sorbent, single-drop
      microextraction and on-line desorption of dried blood spots. Most of these
      published methods are either single-analyte or multicomponent procedures; methods
      intended for systematic toxicological analysis are relatively scarce. However,
      the use of on-line extraction will certainly increase in the near future.

PMID- 25383737
TI  - Current position of high-resolution MS for drug quantification in clinical &
      forensic toxicology.
AB  - This paper reviews high-resolution MS approaches published from January 2011
      until March 2014 for the quantification of drugs (of abuse) and/or their
      metabolites in biosamples using LC-MS with time-of-flight or OrbitrapTM mass
      analyzers. Corresponding approaches are discussed including sample preparation
      and mass spectral settings. The advantages and limitations of high-resolution MS
      for drug quantification, as well as the demand for a certain resolution or a
      specific mass accuracy are also explored.

PMID- 25383738
TI  - Progress in monitoring alcohol consumption and alcohol abuse by
      phosphatidylethanol.
AB  - For early diagnosis and therapy of alcohol-related disorders, alcohol biomarkers
      are highly valuable. Concerning specificity, indirect markers can be influenced
      by nonethanol-related factors, whereas direct markers are only formed after
      ethanol consumption. Sensitivity of the direct markers depends on cut-offs of
      analytical methods, material for analysis and plays an important role for their
      utilization in different fields of application. Until recently, the biomarker
      phosphatidylethanol has been used to differentiate between social drinking and
      alcohol abuse. After method optimization, the detection limit could be lowered
      and phosphatidylethanol became sensitive enough to even detect the consumption of
      low amounts of alcohol. This perspective gives a summary of most common alcohol
      biomarkers and summarizes new developments for monitoring alcohol consumption
      habits.

PMID- 25383740
TI  - Impact of electrospray ion source platforms on matrix effect due to plasma
      phospholipids in the determination of rivastigmine by LC-MS/MS.
AB  - BACKGROUND: This study evaluates the performance of three electrospray ionization
      source designs to monitor the interference of plasma phospholipids for reliable
      estimation of rivastigmine by LC-MS/MS for method ruggedness. The variation in
      the area response due to matrix effects was assessed by post-column infusion,
      post-extraction spiking and standard-line slope methods. RESULTS: The observed
      interference due to coeluting phospholipids (m/z: 524.0/184.0) at the retention
      time of rivastigmine was 39.5, 12.9 and 0.4% using angular spray, orthogonal
      spray and dual orthogonal ion source spray design, respectively. Similarly, %CV
      for standard line slopes was 6.9, 4.6 and 2.0, respectively. CONCLUSION: Z-spray
      source design provided better and efficient transfer of gas phase ions into the
      mass analyzer compared with angular and orthogonal spray. The study showed that Z
      spray ion source provided minimum interference from phospholipids compared with
      other ion source designs.

PMID- 25383741
TI  - An optimal LC-MS/MS method for determination of azithromycin in white blood
      cells: application to pediatric samples.
AB  - BACKGROUND: Studies suggest that particular antimicrobial and anti-inflammatory
      properties of azithromycin (AZM) can be related to its extensive accumulation in
      white blood cells (WBCs). However, available methods for determination of AZM in
      WBCs require large blood volumes unsuited to a pediatric context. Therefore, an
      LC-MS/MS method was developed for determination of AZM in WBCs. RESULTS: WBCs
      were isolated from 500 ul of whole blood by lysing red blood cells. Then, lysis
      of WBCs was performed with methanol/buffer containing AZM-d3-(13)C as internal
      standard. After reversed phase LC, detection was performed under multiple
      reaction monitoring conditions in positive electrospray mode. Linearity ranged
      from 0.5 to 200 ng per WBC sample. Within-run and overall accuracy and precision
      ranged from 95.3 to 101.1% and from 1.6 to 4.7%, respectively. All validation
      parameters fulfilled international requirements. CONCLUSIONS: This method can be
      easily performed on small samples and provides reliable data, including in
      children and neonates.

PMID- 25383742
TI  - Evaluation of the accuracy of ultrasonography fetal weight estimation models;
      assessing regression formulae in a Turkish population.
AB  - In this study, we aimed to evaluate the accuracy of fetal weight prediction, to
      investigate the validity of sonographic fetal anthropometric parameters in a
      Turkish population and to assess the most commonly used sonographic formulas for
      estimation of fetal birth weight. Our retrospective, cross-sectional study
      included 126 singleton deliveries between June 2010 and January 2011, at the
      Department of Obstetrics and Gynecology of the GATA Haydarpasa Training Hospital.
      Ultrasonography measurement results were applied to nine different fetal weight
      estimation formulas. Mean error, mean absolute error, mean percentage error and
      mean absolute percentage error rates were calculated. Under- or overestimation
      rates and correlation coefficients were also calculated. Fetal biparietal
      diameter (BPD) and abdominal circumference (AC) were significantly correlated
      with the actual birth weight and the power analysis for both parameters was
      calculated as 81%. The highest correlation coefficients in our general population
      were those of the F1 (Hadlock 1) and F2 (Hadlock 2) models. The highest mean
      percentage error was detected on F8 (Merz 2) model. Fetal weight estimation
      modalities were observed to give the best results in a weight range of 3,000 and
      3,500 g. Regression formulae used in our population, in general, tended to
      underestimate, however Hadlock 1 and 2 formulations provided the most accurate
      results. The Hadlock 1 formula estimated the closest to the actual birth weight
      in fetuses expected to be born under 3,000 g or over 3,500 g. 

PMID- 25383743
TI  - Zirconium complexes of bipyrrolidine derived salan ligands for the isoselective
      polymerisation of rac-lactide.
AB  - Herein we report the synthesis and characterisation of a series of Zr(IV) 2,2'
      bipyrrolidine-salan derived complexes and their exploitation for the ring opening
      polymerisation of rac-lactide to afford highly isotactically enriched polymers.

PMID- 25383744
TI  - Small cell carcinoma of the prostate: molecular basis and clinical implications.
AB  - Small cell carcinoma of the prostate (PSCC) is a rare and highly aggressive
      malignancy with a dismal prognosis. Most patients present with advanced disease,
      including metastases to bone, viscera, and the central nervous system.
      Histologically, PSCC is indistinguishable from its pulmonary counterpart.
      Although PSCC may occur in pure form, as in small cell lung carcinoma, it also
      occurs in conjunction with conventional glandular prostate carcinoma, and may
      evolve from conventional adenocarcinoma during the course of hormonal therapy.
      Immunohistochemical staining is extremely helpful in establishing the diagnosis,
      a prerequisite, as in small cell lung cancer, for optimal therapeutic strategy.
      Currently, combinations of surgical resection, chemotherapy, and radiation
      therapy represent the main treatment options. Improvement in survival may depend
      upon the identification of new molecular markers to facilitate earlier diagnosis
      and the development of novel targeted therapies. This review will discuss general
      aspects of PSCC, focusing on ways in which our understanding of PSCC has been
      advanced by studies of the histopathologic, immunohistochemical and molecular
      alterations in this disease.

PMID- 25383745
TI  - HIV-infection, atherosclerosis and the inflammatory pathway: candidate gene study
      in a Spanish HIV-infected population.
AB  - BACKGROUND: Higher prevalence of atherosclerosis and higher cardiovascular risk
      is observed in HIV-infected individuals. The biological mechanisms underlying
      these processes are unclear. Several studies have implicated genetic variants in
      the inflammatory genes in cardiovascular disease and in HIV natural course
      infection. METHODS & FINDINGS: In this study we have tested the possible
      association between genetic variants in several inflammatory genes and
      asymptomatic cardiovascular disease measured by carotid intima media thickness
      (cIMT) and atherosclerotic plaque presence as dependent variables in 213 HIV
      infected individuals. A total of 101 genetic variants in 25 candidate genes have
      been genotyped. Results were analyzed using Plink and SPSS statistical packages.
      We have found several polymorphisms in the genes ALOX5 (rs2115819 p = 0.009),
      ALOX5AP (rs9578196 p = 0.007; rs4769873 p = 0.004 and rs9315051 p = 0.0004),
      CX3CL1 (rs4151117 p = 0.040 and rs614230 p = 0.015) and CCL5 (rs3817655 p = 0.018
      and rs2107538 p = 0.018) associated with atherosclerotic plaque. cIMT mean has
      been associated with CRP (1130864 p = 0.0003 and rs1800947 p = 0.008), IL1RN
      (rs380092 p = 0.002) and ALOX5AP (rs3885907 p = 0.02) genetic variants.
      CONCLUSIONS: In this study we have found modest associations between genetic
      variants in several inflammatory genes and atherosclerotic plaque or cIMT.
      Nevertheless, our study adds evidence to the association between inflammatory
      pathway genetic variants and the atherosclerotic disease in HIV-infected
      individuals.

PMID- 25383747
TI  - Synthesis of polysubstituted pyrazoles by a platinum-catalyzed sigmatropic
      rearrangement/cyclization cascade.
AB  - A highly efficient Pt-catalyzed [3,3] sigmatropic rearrangement/cyclization
      cascade of N-propargylhydrazones is reported. The process provides expedient
      access to a variety of highly functionalized pyrazoles. The substrate has good
      substituted group compatibility, and the bioactive 3-CF3 pyrazoles could be
      synthesized easily with this method. 

PMID- 25383746
TI  - Lycopene supplementation reduces TNF-alpha via RAGE in the kidney of obese rats.
AB  - BACKGROUND: The kidney is a target organ for injuries caused by advanced
      glycation end products (AGEs) in obesity. The receptor of AGEs (RAGE) is
      proinflammatory and appears to have a role in the pathogenesis of renal disease
      due to obesity. OBJECTIVE: The aim was to verify the effect of obesity on renal
      damage and the effect of lycopene on these complicationsDesign and Methods:Male
      Wistar rats were randomly assigned to receive a control diet (C, n=7) or a high
      fat diet plus sucrose (HD+S, n=14) for 6 weeks. After this period, the HD+S
      animals were randomized into two groups: HD+S (n=7) and HD+S supplemented with
      lycopene (HD+S+L, n=7). The animals received maize oil (C and HD+S) or lycopene
      (HD+S+L) for a 6-week period. RESULTS: The HD+S and HD+S+L animals demonstrated
      insulin resistance (OGTT glucose after 150 min; C: 117.6+/-3.9<HD+S: 138.1+/
      5.1=HD+S+L: 137.8+/-5.2 mg dl(-1); P=0.01); however, no changes were seen in
      fasting glucose, plasma lipids, blood pressure or renal function. Renal
      concentrations of RAGE and TNF-alpha increased in the HD+S group and lycopene
      supplementation restored these to control group values (RAGE: C: 3.1+/
      0.3=DH+S+L: 3.1+/-0.3<DH+S: 3.6+/-0.4 MUg g(-1); P=0.014; TNF-alpha: C: 227.8+/
      2.7=DH+S+L: 227.4+/-2.2<DH+S: 238.7+/-3.0 pg/ml; P=0.014). CONCLUSIONS: Lycopene
      may be beneficial in the prevention and treatment of oxidative stress and
      inflammation in the kidney due to obesity.

PMID- 25383748
TI  - Effect of rifampicin and gentamicin on Shiga toxin 2 expression level and the SOS
      response in Escherichia coli O104:H4.
AB  - BACKGROUND: A novel pathotype, Shiga toxin-producing Escherichia coli O104:H4,
      was the cause of a severe outbreak that affected European countries, mainly
      Germany, in 2011. The effect of different regimens of rifampicin and gentamicin
      were evaluated to determine possible treatment modes for the novel strain, and to
      evaluate the SOS response and its effect on toxin release. MATERIALS AND METHODS:
      Pulsed-field gel electrophoresis (PFGE) was performed on the novel E. coli
      O104:H4 pathotype and two pre-outbreak E. coli O104:H4 CDC strains. Transcript
      levels of the stx2 and recA gene (SOS response inducer) were evaluated using
      quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR)
      in the novel E. coli O104:H4 samples subjected to different regimens of
      rifampicin and gentamicin. Consequently, reverse passive latex agglutination
      (RPLA) was used to determine the Stx2 titers in these samples. Western blot was
      performed to determine the LexA levels (SOS response repressor) in E. coli
      O104:H4. The efficacy of treatment with antimicrobial agents was assessed in
      BALB/c mice. RESULTS: The outbreak and pre-outbreak strains are closely related
      as shown by PFGE, which demonstrated slight genomic differences between the three
      strains. The transcription level of the stx2 gene in the new pathotype was 1.41-
      and 1.75-fold that of the 2009 EL-2050 and 2009 EL-2071 pre-outbreak strains,
      respectively. Moreover, the transcription level of the stx2 gene in the new
      pathotype was substantially decreased as a result of treatment with the different
      concentrations of the antimicrobial agents, but was enhanced when the antibiotics
      were administered at two subinhibitory levels. RPLA data were in accordance with
      the qRT-PCR results. E. coli O104:H4 exposed to gentamicin at both sub-minimum
      inhibitory concentration (MIC) levels led to high transcription levels of the
      recA gene and lack of expression of the LexA protein, implying that the SOS
      response was activated. Rifampicin at both sub-MIC levels resulted in low
      transcript levels of the recA gene, indicating that the SOS response was not
      induced. In vivo, the highest survival rate in BALB/c mice was observed in the
      group that was treated with the minimum bactericidal concentration (MBC) of
      gentamicin. CONCLUSION: The use of antimicrobial agents in E. coli O104:H4
      infection seems to be effective at the MIC and MBC levels. This provides a
      promising ground for treatment of E. coli O104:H4.

PMID- 25383749
TI  - Fabrication of magnetically recoverable catalysts based on mixtures of Pd and
      iron oxide nanoparticles for hydrogenation of alkyne alcohols.
AB  - We report a novel method for development of magnetically recoverable catalysts
      prepared by thermal decomposition of palladium acetylacetonate in the presence of
      iron oxide nanoparticles (NPs). Depending on conditions, the reaction results
      either in a dispersed mixture of Pd and iron oxide NPs or in their aggregates. It
      was demonstrated that the Pd loading, reaction temperature, solvent, and iron
      oxide NP size and composition are crucial to control the reaction product
      including the degree of aggregation of Pd and iron oxide NPs, and the catalyst
      properties. The aggregation controlled by polarization and magnetic forces allows
      faster magnetic separation, yet the aggregate sizes do not exceed a few hundred
      nanometers, making them suitable for various catalytic applications. These NP
      mixtures were studied in a selective hydrogenation of 2-methyl-3-butyn-2-ol to 2
      methyl-3-buten-2-ol, demonstrating clear differences in catalytic behavior
      depending on the catalyst structure. In addition, one of the catalysts was also
      tested in hydrogenation of 3-methyl-1-pentyn-3-ol and 3-methyl-1-nonyn-3-ol,
      indicating some specificity of the catalyst toward different alkyne alcohols. 

PMID- 25383750
TI  - A novel approach to prepare optically active ion doped luminescent materials via
      electron beam evaporation into ionic liquids.
AB  - A novel approach to prepare luminescent materials via electron-beam evaporation
      into ionic liquids is presented which even allows doping of host lattices with
      ions that have a strong size mismatch. To prove this, MgF2 nanoparticles doped
      with Eu(3+) were fabricated. The obtained nanoparticles featured an unusually
      high luminescence lifetime and the obtained material showed a high potential for
      application. 

PMID- 25383751
TI  - Resistance to instructed reversal of the learned predictiveness effect.
AB  - The learned predictiveness effect is a widely observed bias towards previously
      predictive cues in novel situations. Although the effect is generally attributed
      to an automatic attentional shift, it has recently been explained as the product
      of controlled inferences about the predictive value of cues. This view is
      supported by the susceptibility of learned predictiveness to instruction
      manipulation. However, recent research has shown conflicting results. Three
      experiments investigated the parameters of the instructed reversal effect in a
      human causal learning task, to determine the relative contribution of automatic
      and controlled attention processes. Experiment 1 showed that reversal
      instructions abolished, but did not reverse, the learned predictiveness effect,
      although length of initial training had no effect on the extent to which
      predictive cues subsequently captured attention. Experiment 2 explored whether
      particular causal scenarios lend themselves more readily to instructed reversal,
      but still failed to establish a significant reversal effect. Experiment 3
      demonstrated a significant reversal effect when nonpredictive cues were
      explicitly and individually identified as the causes of outcomes. However, this
      effect was considerably weaker than the learned predictiveness effect when
      predictive cues were identified in the same way. Taken together, the results are
      inconsistent with a purely controlled account of learned predictiveness and
      provide support for dual-process theories of learning and attention. 

PMID- 25383752
TI  - Antimicrobial activity of UV-induced phenylamides from rice leaves.
AB  - Rice produces a wide array of phytoalexins in response to pathogen attacks and UV
      irradiation. Except for the flavonoid sakuranetin, most phytoalexins identified
      in rice are diterpenoid compounds. Analysis of phenolic-enriched fractions from
      UV-treated rice leaves showed that several phenolic compounds in addition to
      sakuranetin accumulated remarkably in rice leaves. We isolated two compounds from
      UV-treated rice leaves using silica gel column chromatography and preparative
      HPLC. The isolated phenolic compounds were identified as phenylamide compounds: N
      trans-cinnamoyltryptamine and N-p-coumaroylserotonin. Expression analysis of
      biosynthetic genes demonstrated that genes for arylamine biosynthesis were
      upregulated by UV irradiation. This result suggested that phenylamide
      biosynthetic pathways are activated in rice leaves by UV treatment. To unravel
      the role of UV-induced phenylamides as phytoalexins, we examined their
      antimicrobial activity against rice fungal and bacterial pathogens. N-trans
      Cinnamoyltryptamine inhibited the growth of rice brown spot fungus (Bipolaris
      oryzae). In addition to the known antifungal activity to the blast fungus,
      sakuranetin had antimicrobial activity toward B. oryzae and Rhizoctonia solani
      (rice sheath blight fungus). UV-induced phenylamides and sakuranetin also had
      antimicrobial activity against rice bacterial pathogens for grain rot
      (Burkholderia glumae), blight (Xanthomonas oryzae pv. oryzae) and leaf streak (X.
      oryzae pv. oryzicola) diseases. These findings suggested that the UV-induced
      phenylamides in rice are phytoalexins against a diverse array of pathogens. 

PMID- 25383753
TI  - Novel flavonol glycosides from the aerial parts of lentil (Lens culinaris).
AB  - While the phytochemical composition of lentil (Lens culinaris) seeds is well
      described in scientific literature, there is very little available data about
      secondary metabolites from lentil leaves and stems. Our research reveals that the
      aerial parts of lentil are a rich source of flavonoids. Six kaempferol and twelve
      quercetin glycosides were isolated, their structures were elucidated using NMR
      spectroscopy and chemical methods. This group includes 16 compounds which have
      not been previously described in the scientific literature: quercetin 3-O-beta-D
      glucopyranosyl(1->2)-beta-D-galactopyranoside-7-O-beta-D-glucuropyranoside (1),
      kaempferol 3-O-beta-D-glucopyranosyl(1->2)-beta-D-galacto-pyranoside-7-O-beta-D
      glucuropyranoside (3), their derivatives 4-10,12-15,17,18 acylated with caffeic,
      p-coumaric, ferulic, or 3,4,5-trihydroxycinnamic acid and kaempferol 3-O-{[(6-O-E
      p-coumaroyl)-beta-D-glucopyranosyl(1->2)]-alpha-L-rhamnopyranosyl(1->6)}-beta-D
      galactopyranoside-7-O-alpha-L-rhamnopyranoside (11). Their DPPH scavenging
      activity was also evaluated. This is probably the first detailed description of
      flavonoids from the aerial parts of lentil. 

PMID- 25383754
TI  - Icariin is a PPARalpha activator inducing lipid metabolic gene expression in
      mice.
AB  - Icariin is effective in the treatment of hyperlipidemia. To understand the effect
      of icariin on lipid metabolism, effects of icariin on PPARalpha and its target
      genes were investigated. Mice were treated orally with icariin at doses of 0,
      100, 200, and 400 mg/kg, or clofibrate (500 mg/kg) for five days. Liver total RNA
      was isolated and the expressions of PPARalpha and lipid metabolism genes were
      examined. PPARalpha and its marker genes Cyp4a10 and Cyp4a14 were induced 2-4
      fold by icariin, and 4-8 fold by clofibrate. The fatty acid (FA) binding and co
      activator proteins Fabp1, Fabp4 and Acsl1 were increased 2-fold. The mRNAs of
      mitochondrial FA beta-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2) were
      increased 2-3 fold. The mRNAs of proximal beta-oxidation enzymes (Acox1, Ech1,
      and Ehhadh) were also increased by icariin and clofibrate. The expression of
      mRNAs for sterol regulatory element-binding factor-1 (Srebf1) and FA synthetase
      (Fasn) were unaltered by icariin. The lipid lysis genes Lipe and Pnpla2 were
      increased by icariin and clofibrate. These results indicate that icariin is a
      novel PPARalpha agonist, activates lipid metabolism gene expressions in liver,
      which could be a basis for its lipid-lowering effects and its beneficial effects
      against diabetes. 

PMID- 25383755
TI  - UV-absorption--the primary process in photocatalysis and some practical
      consequences.
AB  - TiO2 photochemistry studies generally address reactions of photogenerated charge
      carriers at the oxide surface or the recombination reactions which control the
      proportion of charge carriers that reach the surface. By contrast, this review
      focuses on UV absorption, the first photochemical step in semiconductor
      photocatalysis. The influence of particle size on absorption and scattering of
      light by small TiO2 particles is summarized and the importance of considering,
      the particle size in the application, not the BET or X-ray line broadening size,
      is emphasized. Three different consequences of UV absorption are then considered.
      First, two commercially important systems, pigmented polymer films and paints,
      are used to show that TiO2 can protect from direct photochemical degradation.
      Then the effect of UV absorption on the measured photocatalytic degradation of
      aqueous solutions of organics is considered for two separate cases. Firstly, the
      consequences of UV absorption by TiO2 on the generation of hydroxyl radicals from
      H2O2 are considered in the context of the claimed synergy between H2O2 and TiO2.
      Secondly, the effect of altered UV absorption, caused by changed effective
      particle size of the catalyst, is demonstrated for photocatalysis of propan-2-ol
      oxidation and salicylic acid degradation. 

PMID- 25383756
TI  - Enzyme regulation: a thiol switch opens the gate.

PMID- 25383757
TI  - A redox switch shapes the Lon protease exit pore to facultatively regulate
      proteolysis.
AB  - The Lon AAA+ protease degrades damaged or misfolded proteins in its
      intramolecular chamber. Its activity must be precisely controlled, but the
      mechanism by which Lon is regulated in response to different environments is not
      known. Facultative anaerobes in the Enterobacteriaceae family, mostly symbionts
      and pathogens, encounter both anaerobic and aerobic environments inside and
      outside the host's body, respectively. The bacteria characteristically have two
      cysteine residues on the Lon protease (P) domain surface that unusually form a
      disulfide bond. Here we show that the cysteine residues act as a redox switch of
      Lon. Upon disulfide bond reduction, the exit pore of the P-domain ring narrows by
      ~30%, thus interrupting product passage and decreasing activity by 80%; disulfide
      bonding by oxidation restores the pore size and activity. The redox switch (E
      degrees ' = -227 mV) is appropriately tuned to respond to variation between
      anaerobic and aerobic conditions, thus optimizing the cellular proteolysis level
      for each environment. 

PMID- 25383760
TI  - The consequences for human health of stratospheric ozone depletion in association
      with other environmental factors.
AB  - Due to the implementation of the Montreal Protocol, which has limited, and is now
      probably reversing, the depletion of the stratospheric ozone layer, only modest
      increases in solar UV-B radiation at the surface of the Earth have occurred. For
      many fair-skinned populations, changing behaviour with regard to exposure to the
      sun over the past half century - more time in the sun, less clothing cover (more
      skin exposed), and preference for a tan - has probably contributed more to
      greater levels of exposure to UV-B radiation than ozone depletion. Exposure to UV
      B radiation has both adverse and beneficial effects on human health. This report
      focuses on an assessment of the evidence regarding these outcomes that has been
      published since our previous report in 2010. The skin and eyes are the organs
      exposed to solar UV radiation. Excessive solar irradiation causes skin cancer,
      including cutaneous malignant melanoma and the non-melanoma skin cancers, basal
      cell carcinoma and squamous cell carcinoma, and contributes to the development of
      other rare skin cancers such as Merkel cell carcinoma. Although the incidence of
      melanoma continues to increase in many countries, in some locations, primarily
      those with strong sun protection programmes, incidence has stabilised or
      decreased over the past 5 years, particularly in younger age-groups. However, the
      incidence of non-melanoma skin cancers is still increasing in most locations.
      Exposure of the skin to the sun also induces systemic immune suppression that may
      have adverse effects on health, such as through the reactivation of latent viral
      infections, but also beneficial effects through suppression of autoimmune
      reactivity. Solar UV-B radiation damages the eyes, causing cataracts and
      pterygium. UV-B irradiation of the skin is the main source of vitamin D in many
      geographic locations. Vitamin D plays a critical role in the maintenance of
      calcium homeostasis in the body; severe deficiency causes the bone diseases,
      rickets in children and osteomalacia in adults. Although many studies have
      implicated vitamin D deficiency in a wide range of diseases, such as cancer and
      cardiovascular disease, more recent evidence is less compelling, with meta
      analyses of supplementation trials failing to show a beneficial effect on the
      health outcomes that have been tested. It continues to be difficult to provide
      public health messages to guide safe exposure to the sun that are accurate,
      simple, and can be used by people with different skin types, in different
      locations, and for different times of the year or day. There is increasing
      interest in relating sun protection messages to the UV Index. Current sun
      protection strategies are outlined and assessed. Climatic factors affect the
      amount of UV radiation received by the skin and eyes, separately from the effect
      of ozone depletion. For example, cloud cover can decrease or increase the
      intensity of UV radiation at Earth's surface and warmer temperatures and changes
      in precipitation patterns may alter the amount of time people spend outdoors and
      their choice of clothing. The combination of changes in climate and UV radiation
      may affect the number of pathogenic microorganisms in surface waters, and could
      have an impact on food security through effects on plant and aquatic systems. It
      remains difficult to quantify these effects and their possible importance for
      human health. 

PMID- 25383758
TI  - Terazosin activates Pgk1 and Hsp90 to promote stress resistance.
AB  - Drugs that can protect against organ damage are urgently needed, especially for
      diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a
      widely marketed alpha1-adrenergic receptor antagonist, alleviated organ damage
      and improved survival in rodent models of stroke and sepsis. Through combined
      studies of enzymology and X-ray crystallography, we discovered that TZ binds a
      new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic
      activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to
      promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may
      enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1.
      Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate
      that TZ has a new protein target, Pgk1, and reveal its corresponding biological
      effect. As a clinical drug, TZ may be quickly translated into treatments for
      diseases including stroke and sepsis. 

PMID- 25383759
TI  - LRAT-specific domain facilitates vitamin A metabolism by domain swapping in
      HRASLS3.
AB  - Cellular uptake of vitamin A, production of visual chromophore and triglyceride
      homeostasis in adipocytes depend on two representatives of the vertebrate
      N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like
      tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing
      enzymes but differ in their substrate preferences and dominant catalytic
      activity. The mechanism of this catalytic diversity is not understood. Here, by
      using a gain-of-function approach, we identified a specific sequence responsible
      for the substrate specificity of N1pC/P60 proteins. A 2.2-A crystal structure of
      the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state
      revealed a major structural rearrangement accompanied by three-dimensional domain
      swapping dimerization not observed in native HRASLS proteins. Structural changes
      affecting the active site environment contributed to slower hydrolysis of the
      catalytic intermediate, supporting efficient acyl transfer. These findings reveal
      structural adaptation that facilitates selective catalysis and mechanism
      responsible for diverse substrate specificity within the LRAT-like enzyme family.

PMID- 25383761
TI  - Secondhand tobacco smoke exposure among hospitalized nonsmokers with coronary
      heart disease.

PMID- 25383762
TI  - Carbon quantum dot stabilized gadolinium nanoprobe prepared via a one-pot
      hydrothermal approach for magnetic resonance and fluorescence dual-modality
      bioimaging.
AB  - Magnetic resonance imaging (MRI) is used extensively for clinical diagnoses. It
      is critical to design and develop highly efficient MR contrast agents with simple
      preparation procedure, low toxicity, and high biocompatibility. Here, we report a
      carbon quantum dots (CQDs)-stabilized gadolinium hybrid nanoprobe (Gd-CQDs)
      prepared via a one-pot hydrothermal treatment of the mixture of citrate acid,
      ethanediamine, and GdCl3 at 200  degrees C for 4 h. In vitro and in vivo tests
      confirmed their low toxicity and high biocompatibility. Gd-CQDs were observed to
      have a higher MR response than gadopentetic acid dimeglumine (Gd-DTPA) because of
      their high Gd content and hydrophilicity. Moreover, the fluorescence of CQDs was
      remained in Gd-CQDs. The in vivo MR and fluorescence dual-modality imaging of Gd
      CQDs was confirmed with zebrafish embryo and mice as models. The modification of
      Gd-CQDs with arginine-glycine-aspartic acid (RGD) tripeptide provided a high
      affinity to U87 cancer cells for targeted imaging. Whereas the MR response showed
      a depth penetration and spatial visualization, fluorescence revealed the fine
      distribution of Gd-CQDs in tissues because of its high resolution and
      sensitivity. We found that Gd-CQDs distributed in the tissues in a heterogeneous
      mode: they entered into the tissue cells but were observed less in the
      extracellular matrix. The MR and fluorescence dual-modality imaging of Gd-CQDs
      makes them a potential contrast agent for clinic applications because of their
      simple preparation procedure, ease of functionalization, high contrast
      efficiency, low toxicity, and high biocompatibility. 

PMID- 25383763
TI  - Thermo-responsive white-light emission based on tetraphenylethylene- and
      rhodamine B-containing boronate nanoparticles.
AB  - Boronate nanoparticles with built-in tetraphenylethylene (TPE) have been
      prepared. Their emissive color tuning by altering the amount of rhodamine B
      grafted onto the surface gave white-light emissive nanoparticles. They showed
      reversible and thermo-responsive emission in the temperature range of 5-65 
      degrees C in water, which enabled them to serve as a bright nanothermometer. 

PMID- 25383764
TI  - Traditional Masculinity as a Risk Factor for Suicidal Ideation: Cross-Sectional
      and Prospective Evidence from a Study of Young Adults.
AB  - Traditional masculinity is hypothesized to be associated with suicidal ideation,
      and traditional masculinity is predicted to interact with stressors, intensifying
      suicidal ideation. Cross-sectional and prospective data from a study of 2,431
      young adults was analyzed using hierarchical regression main effects and
      interaction models. Traditional masculinity was associated with suicidal
      ideation, second only in strength to depression, including when controlling for
      other risk factors. Prospective effects were substantially weaker. There was
      mixed evidence for traditional masculinity by stress interactions. The results
      provide preliminary support for the role of traditional masculinity in suicidal
      ideation, but the relationship should be tested in studies of suicide attempts
      and mortality. Implications for prevention and intervention are explored. 

PMID- 25383765
TI  - Bullying in authorship: abusive mentorship and undeserved credit.

PMID- 25383766
TI  - Estimation of clustering parameters using gaussian process regression.
AB  - We propose a method for estimating the clustering parameters in a Neyman-Scott
      Poisson process using Gaussian process regression. It is assumed that the
      underlying process has been observed within a number of quadrats, and from this
      sparse information the distribution is modelled as a Gaussian process. The
      clustering parameters are then estimated numerically by fitting to the covariance
      structure of the model. It is shown that the proposed method is resilient to any
      sampling regime. The method is applied to simulated two-dimensional clustered
      populations and the results are compared to a related method from the literature.

PMID- 25383767
TI  - KORRIGAN1 interacts specifically with integral components of the cellulose
      synthase machinery.
AB  - Cellulose is synthesized by the so called rosette protein complex and the
      catalytic subunits of this complex are the cellulose synthases (CESAs). It is
      thought that the rosette complexes in the primary and secondary cell walls each
      contains at least three different non-redundant cellulose synthases. In addition
      to the CESA proteins, cellulose biosynthesis almost certainly requires the action
      of other proteins, although few have been identified and little is known about
      the biochemical role of those that have been identified. One of these proteins is
      KORRIGAN (KOR1). Mutant analysis of this protein in Arabidopsis thaliana showed
      altered cellulose content in both the primary and secondary cell wall. KOR1 is
      thought to be required for cellulose synthesis acting as a cellulase at the
      plasma membrane-cell wall interface. KOR1 has recently been shown to interact
      with the primary cellulose synthase rosette complex however direct interaction
      with that of the secondary cell wall has never been demonstrated. Using various
      methods, both in vitro and in planta, it was shown that KOR1 interacts
      specifically with only two of the secondary CESA proteins. The KOR1 protein
      domain(s) involved in the interaction with the CESA proteins were also identified
      by analyzing the interaction of truncated forms of KOR1 with CESA proteins. The
      KOR1 transmembrane domain has shown to be required for the interaction between
      KOR1 and the different CESAs, as well as for higher oligomer formation of KOR1. 

PMID- 25383768
TI  - High levels of soluble CTLA-4 are present in anti-mitochondrial antibody
      positive, but not in antibody negative patients with primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease
      frequently characterized by anti-mitochondrial autoantibodies (AMA). A minority
      of patients are AMA-negative. Cytotoxic-T-Lymphocyte-Antigen-4 (CTLA-4) is a
      surface molecule expressed on activated T-cells delivering a critical negative
      immunoregulatory signal. A soluble form of CTLA-4 (sCTLA-4) has been detected at
      high concentrations in several autoimmune diseases, and its possible functional
      meaning has been suggested. We aimed to evaluate sCTLA-4 concentration in sera of
      patients with PBC and to correlate it to immunological abnormalities associated
      with the disease. Blood samples were collected from 82 PBC-patients diagnosed
      according to international criteria (44 AMA-positive/MIT3-positive and 38 AMA
      negative-MIT3-negative), and 65 controls. sCTLA-4 levels were evaluated by ELISA
      and Western blot. Increased sCTLA-4 concentrations were found in all AMA-positive
      PBC-patients, but in none of the AMA-negative ones, nor in normal controls or in
      controls with unrelated liver diseases. sCTLA-4 presence was associated with
      autoantibodies against MIT3, but not with nuclear autoantibodies (sp100, gp210).
      This is the first study to demonstrate that levels of sCTLA-4 are elevated in
      sera of PBC patients. However, they are clearly restricted to patients with AMA
      positivity, suggesting an immunological difference with respect to AMA-negative
      ones. 

PMID- 25383774
TI  - Imaging blood-brain barrier dysfunction in football players.

PMID- 25383775
TI  - The central clock in patients with Parkinson disease.

PMID- 25383770
TI  - Congenital anomalies and in utero antiretroviral exposure in human
      immunodeficiency virus-exposed uninfected infants.
AB  - IMPORTANCE: Most studies examining the association of prenatal antiretroviral
      (ARV) exposures with congenital anomalies (CAs) in children born to human
      immunodeficiency virus (HIV)-infected women have been reassuring, but some
      evidence suggests an increased risk with specific ARV agents. OBJECTIVE: To
      evaluate the association of in utero ARV exposures with CAs in HIV-exposed
      uninfected children. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study
      design. The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART
      Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV
      exposed uninfected children enrolled in the SMARTT Study between March 23, 2007,
      and June 18, 2012. EXPOSURES: First-trimester exposure to any ARV and to specific
      ARV medications. MAIN OUTCOMES AND MEASURES: The primary end point was a CA based
      on physician review of infant physical examinations according to the
      Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta
      Congenital Defects Program. Rates of CAs were estimated overall and by birth
      year. Logistic regression models were used to evaluate the association of CAs
      with first-trimester ARV exposures, adjusting for demographic and maternal
      characteristics. RESULTS: Congenital anomalies occurred in 175 of 2580 children,
      yielding a prevalence of 6.78% (95% CI, 5.85%-7.82%); 242 major CAs were
      confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence
      of CAs increased significantly among successive birth cohorts (3.8% for children
      born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no
      association of first-trimester exposures with CAs was found for any ARV, for
      combination ARV regimens, or for any drug class. No individual ARV in the reverse
      transcriptase inhibitor drug classes was associated with an increased risk of
      CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir
      sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir
      used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir
      exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55)
      CAs. CONCLUSIONS AND RELEVANCE: Few individual ARVs and no drug classes were
      associated with an increased risk of CAs in HIV-exposed infants after adjustment
      for calendar year and maternal characteristics. While the overall risk remained
      low, a relative increase was observed in successive years and with atazanavir
      exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy
      use during pregnancy still outweigh such risks, although further studies are
      warranted.

PMID- 25383776
TI  - The central clock in patients with Parkinson disease--reply.

PMID- 25383779
TI  - Discovery of pentacyclic triterpenoids as potential entry inhibitors of influenza
      viruses.
AB  - Entry inhibitors are of particular importance in current efforts to develop a new
      generation of anti-influenza virus drugs. Here we report certain pentacyclic
      triterpenes exhibiting conserved structure features and with in vitro anti
      influenza virus activity comparable to and even higher than that of oseltamivir.
      Mechanistic studies indicated that these lead triterpenoids bind tightly to the
      viral envelope hemagglutinin (HA), disrupting the interaction of HA with the
      sialic acid receptor and thus the attachment of viruses to host cells. Docking
      studies suggest that the binding pocket within HA for sialic acid receptor
      potentially acts as a targeting domain, and this is supported by structure
      activity data, sialic acid competition studies, and broad anti-influenza spectrum
      as well as less induction of drug resistance. Our study might establish the
      importance of triterpenoids for development of entry inhibitors of influenza
      viruses. 

PMID- 25383780
TI  - Implementing direct access to low-dose computed tomography in general practice-
      method, adaption and outcome.
AB  - BACKGROUND: Early detection of lung cancer is crucial as the prognosis depends on
      the disease stage. Chest radiographs has been the principal diagnostic tool for
      general practitioners (GPs), but implies a potential risk of false negative
      results, while computed tomography (CT) has a higher sensitivity. The aim of this
      study was to describe the implementation of direct access to low-dose CT (LDCT)
      from general practice. METHODS: We conducted a cohort study nested in a
      randomised study. A total of 119 general practices with 266 GPs were randomised
      into two groups. Intervention GPs were offered direct access to chest LDCT
      combined with a Continuing Medical Education (CME) meeting on lung cancer
      diagnosis. RESULTS: During a 19-month period, 648 patients were referred to LDCT
      (0.18/1000 adults on GP list/month). Half of the patients needed further
      diagnostic work-up, and 15 (2.3%, 95% CI: 1.3-3.8%) of the patients had lung
      cancer; 60% (95% CI: 32.3-83.7%) in a localised stage. The GP referral rate was
      61% higher for CME participants compared to non-participants. CONCLUSION: Of all
      patients referred to LDCT, 2.3% were diagnosed with lung cancer with a favourable
      stage distribution. Half of the referred patients needed additional diagnostic
      work-up. There was an association between participation in CME and use of CT
      scan. The proportion of cancers diagnosed through the usual fast-track evaluation
      was 2.2 times higher in the group of CME-participating GPs. The question remains
      if primary care case-finding with LDCT is a better option for patients having
      signs and symptoms indicating lung cancer than a screening program. Whether open
      access to LDCT may provide earlier diagnosis of lung cancer is yet unknown and a
      randomised trial is required to assess any effect on outcome. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01527214.

PMID- 25383781
TI  - Deletion of apoptosis signal-regulating kinase 1 (ASK1) protects pancreatic beta
      cells from stress-induced death but not from glucose homeostasis alterations
      under pro-inflammatory conditions.
AB  - BACKGROUND: Type 2 diabetes is characterized by pancreatic beta-cell dysfunction
      and is associated with low-grade inflammation. Recent observations suggest that
      apoptosis signal-regulating kinase 1 (ASK1) is involved in beta-cell death in
      response to different stressors. In this study, we tested whether ASK1 deficiency
      protects beta-cells from glucolipotoxic conditions and cytokines treatment or
      from glucose homeostasis alteration induced by endotoxemia. METHODOLOGY/PRINCIPAL
      FINDINGS: Insulin secretion was neither affected upon shRNA-mediated
      downregulation of ASK1 in MIN6 cells nor in islets from ASK1-deficient mice. ASK1
      silencing in MIN6 cells and deletion in islets did not prevent the deleterious
      effect of glucolipotoxic conditions or cytokines on insulin secretion. However,
      it protected MIN6 cells from death induced by ER stress or palmitate and islets
      from short term caspase activation in response to cytokines. Moreover,
      endotoxemia induced by LPS infusion increased insulin secretion during
      hyperglycemic clamps but the response was similar in wild-type and ASK1-deficient
      mice. Finally, insulin sensitivity in the presence of LPS was not affected by
      ASK1-deficiency. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that ASK1 is
      not involved in beta-cell function and dysfunction but controls stress-induced
      beta-cell death.

PMID- 25383782
TI  - Association studies with imputed variants using expectation-maximization
      likelihood-ratio tests.
AB  - Genotype imputation has become standard practice in modern genetic studies. As
      sequencing-based reference panels continue to grow, increasingly more markers are
      being well or better imputed but at the same time, even more markers with
      relatively low minor allele frequency are being imputed with low imputation
      quality. Here, we propose new methods that incorporate imputation uncertainty for
      downstream association analysis, with improved power and/or computational
      efficiency. We consider two scenarios: I) when posterior probabilities of all
      potential genotypes are estimated; and II) when only the one-dimensional summary
      statistic, imputed dosage, is available. For scenario I, we have developed an
      expectation-maximization likelihood-ratio test for association based on posterior
      probabilities. When only imputed dosages are available (scenario II), we first
      sample the genotype probabilities from its posterior distribution given the
      dosages, and then apply the EM-LRT on the sampled probabilities. Our simulations
      show that type I error of the proposed EM-LRT methods under both scenarios are
      protected. Compared with existing methods, EM-LRT-Prob (for scenario I) offers
      optimal statistical power across a wide spectrum of MAF and imputation quality.
      EM-LRT-Dose (for scenario II) achieves a similar level of statistical power as EM
      LRT-Prob and, outperforms the standard Dosage method, especially for markers with
      relatively low MAF or imputation quality. Applications to two real data sets, the
      Cebu Longitudinal Health and Nutrition Survey study and the Women's Health
      Initiative Study, provide further support to the validity and efficiency of our
      proposed methods. 

PMID- 25383783
TI  - Bi-functional biobased packing of the cassava starch, glycerol, licuri
      nanocellulose and red propolis.
AB  - The aim of this study was to characterize and determine the bi-functional
      efficacy of active packaging films produced with starch (4%) and glycerol (1.0%),
      reinforced with cellulose nanocrystals (0-1%) and activated with alcoholic
      extracts of red propolis (0.4 to 1.0%). The cellulose nanocrystals used in this
      study were extracted from licuri leaves. The films were characterized using
      moisture, water-activity analyses and water vapor-permeability tests and were
      tested regarding their total phenolic compounds and mechanical properties. The
      antimicrobial and antioxidant efficacy of the films were evaluated by monitoring
      the use of the active films for packaging cheese curds and butter, respectively.
      The cellulose nanocrystals increased the mechanical strength of the films and
      reduced the water permeability and water activity. The active film had an
      antimicrobial effect on coagulase-positive staphylococci in cheese curds and
      reduced the oxidation of butter during storage. 

PMID- 25383784
TI  - A Novel Compound-Heterozygous Epithelial Cell Adhesion Molecule Mutation in
      Tufting Enteropathy.

PMID- 25383785
TI  - Genetic and electrophysiological characteristics of recurrent acute pancreatitis.
AB  - OBJECTIVES: The aim was to present the workup of patients with acute recurrent
      pancreatitis (ARP) for genetic analysis and electrophysiological testing.
      METHODS: Patients with ARP with unknown etiology were referred for genetic
      testing and evaluation of cystic fibrosis transmembrane conductor regulator
      (CFTR) function by nasal potential difference (NPD) testing. RESULTS: A total of
      67 patients were evaluated. The mean age was 23 +/- 17 years (median 17.0 years,
      range 1.5-72 years); 90% were Jewish and 10% Arab. Ten (15%) patients carried
      PRSS1 gene mutation (K23R(7), R122H(2), and D21A(1)). One patient had K172E/-
      (chymotrypsin C [CTRC]) mutation, 1 had I42M (serine protease inhibitor Kazal
      type 1 [SPINK1])/V235I (CTRC) together with DeltaF508/5T, 1 patient had R67H
      (SPINK1)/V235I (CTRC), and 1 patient had V235I (CTRC)/-. Ten of 67 (15%) patients
      submitted for CFTR gene testing carried mutations (DeltaF508/L997F,
      DeltaF508/5T(11TG), W1282/5T(12TG), W1282X/Y1014C, DeltaF508/R31C, R117H/-,
      R117H/Y1014C, D1152H/-, 5T(11TG)/-, and L997F/-). Fifty-four (80%) patients
      underwent sweat testing. Of these, 5 had sweat chloride >=60 mEq/L, and 22
      patients had sweat chloride from 40 to 60 mEq/L. Of the 56 (83%) patients had
      nasal potential difference testing, 4 (6%) with abnormal results. CONCLUSIONS:
      One-third (34%) of patients with ARP carry mutations for hereditary pancreatitis
      including rare mutations (K23R), and 12.5% have evidence of cftr mutations and
      10% had CFTR dysfunction underscoring the importance of genetic and functional
      workup of these patients.

PMID- 25383787
TI  - Liver biopsy in children: position paper of the ESPGHAN Hepatology Committee.
AB  - Liver biopsy (LB) is still the criterion standard procedure for obtaining liver
      tissue for histopathological examination and a valuable tool in the diagnosis,
      prognosis, and management of many parenchymal liver diseases. The aim of this
      position paper is to summarise the present practice of paediatric LB and make
      recommendations about its performance. Although histological evaluation of the
      liver is important in assessing prognosis and exploring treatment, noninvasive
      techniques (ie, imaging, laboratory markers) may replace use of liver histology.
      The indications for LB are changing as present knowledge of aetiologies,
      pathomechanism, and therapeutic options in paediatric liver disease is evolving.
      Adult and paediatric literature was reviewed to assess the existing clinical
      practice of LB with focus on the technique, indications, risk of complications,
      and contraindications in paediatrics. This position paper presents types of LB,
      indications, complications, contraindications, and an essential checklist for
      paediatric LB. 

PMID- 25383786
TI  - Bile acid pool dynamics in progressive familial intrahepatic cholestasis with
      partial external bile diversion.
AB  - OBJECTIVES: Partial external bile diversion (PEBD) is an established therapy for
      low-gamma-glutamyl transferase (GGT) progressive familial intrahepatic
      cholestasis (PFIC). This study sought to determine whether the dynamics of the
      cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in subjects with low-GGT
      PFIC with successful PEBD were equivalent to those achieved with successful liver
      transplantation (LTX). METHODS: The kinetics of CA and CDCA metabolism were
      measured by stable isotope dilution in plasma samples in 5 subjects with PEBD,
      all with intact canalicular bile salt export pump expression and compared with
      subjects with low-GGT-PFIC with successful LTX. Stomal loss of bile acids was
      measured in subjects with PEBD. RESULTS: The fractional turnover rate for CA in
      the PEBD group ranged from 0.5 to 4.2/day (LTX group, range 0.2-0.9/day, P =
      0.076) and for CDCA from 0.7 to 4.5/day (LTX group 0.3-0.4/day, P = 0.009). The
      CA and CDCA pool sizes were equivalent between groups; however, pool composition
      in PEBD was somewhat more hydrophilic. The CA/CDCA ratio in PEBD ranged from 0.9
      to 19.5, whereas in LTX it ranged from 0.5 to 2.6. Synthesis rates computed from
      isotope dilution correlated well with timed output for both CA (r2 = 0.760, P =
      0.024) and CDCA (r2 = 0.690, P = 0.021). CONCLUSIONS: PEBD results in bile acid
      fractional turnover rates greater than LTX, pool sizes equivalent to LTX, and
      pool composition that is at least as hydrophilic as produced by LTX.

PMID- 25383788
TI  - Thermochemistry of dihalogen-substituted benzenes: data evaluation using
      experimental and quantum chemical methods.
AB  - Temperature dependence of vapor pressures for 12 dihalogen-substituted benzenes
      (halogen = F, Cl, Br, I) was studied by the transpiration method, and molar
      vaporization or sublimation enthalpies were derived. These data together with
      results available in the literature were collected and checked for internal
      consistency using structure-property correlations. Gas-phase enthalpies of
      formation of dihalogen-substituted benzenes were calculated by using quantum
      chemical methods. Evaluated vaporization enthalpies in combination with gas-phase
      enthalpies of formation were used for estimation liquid-phase enthalpies of
      formation of dihalogen-substituted benzenes. Pairwise interactions of halogens on
      the benzene ring were derived and used for development of simple group additivity
      procedures for estimation of vaporization enthalpies, gas-phase, and liquid-phase
      enthalpies of formation of dihalogen-substituted benzenes. 

PMID- 25383789
TI  - Otoliths of five extant species of the annual killifish Nothobranchius from the
      East African savannah.
AB  - This study presents, for the first time, a comprehensive dataset that documents
      the range of inter- and intraspecific otolith variation in aplocheiloid
      killifish, based on a total of 86 individuals representing five extant species of
      Nothobranchius PETERS, 1868, from East Africa: the sympatric pairs N. rubripinnis
      SEEGERS, 1986 and N. ruudwildekampi COSTA, 2009 (Eastern Tanzania), and N.
      orthonotus (PETERS, 1844) and N. furzeri JUBB, 1971 (Southern Mozambique), and
      two isolated populations of N. korthausae MEINKEN, 1973 (Eastern Tanzania).
      Otolith characters were analysed based on SEM images, and otolith morphometry was
      conducted using uni- and multivariate statistics. Two ancient clades of probably
      Early to Middle Miocene age in eastern Tanzania and southern Mozambique can be
      recognized based on otolith morphologies, which is consistent with previous work
      based on molecular data. The distinctive sulcus morphologies in the otoliths of
      sympatric species may be linked to species-specific hearing capabilities, perhaps
      constituting a case of character displacement in an area of secondary sympatry.
      The otoliths of the studied species of Nothobranchius are diagnostic at the
      species level, even in the case of closely related species diagnosable otherwise
      only by minor differences in coloration. The two populations of N. korthausae
      also displayed some differences in their otolith characters. The new data may
      facilitate future recognition of fossil species of Nothobranchius. As no fossil
      remains of extant aplocheiloid killifishes have yet been described, the discovery
      of fossil otoliths of Nothobranchius would significantly advance understanding of
      the evolutionary history of this interesting group of fishes. 

PMID- 25383791
TI  - Field demonstration of CO2 leakage detection in potable aquifers with a pulselike
      CO2-release test.
AB  - This study presents two field pulselike CO2-release tests to demonstrate CO2
      leakage detection in a shallow aquifer by monitoring groundwater pH, alkalinity,
      and dissolved inorganic carbon (DIC) using the periodic groundwater sampling
      method and a fiber-optic CO2 sensor for real-time in situ monitoring of dissolved
      CO2 in groundwater. Measurements of groundwater pH, alkalinity, DIC, and
      dissolved CO2 clearly deviated from their background values, showing responses to
      CO2 leakage. Dissolved CO2 observed in the tests was highly sensitive in
      comparison to groundwater pH, DIC, and alkalinity. Comparison of the pulselike
      CO2-release tests to other field tests suggests that pulselike CO2-release tests
      can provide reliable assessment of geochemical parameters indicative of CO2
      leakage. Measurements by the fiber-optic CO2 sensor, showing obvious leakage
      signals, demonstrated the potential of real-time in situ monitoring of dissolved
      CO2 for leakage detection at a geologic carbon sequestration (GCS) site. Results
      of a two-dimensional reactive transport model reproduced the geochemical
      measurements and confirmed that the decrease in groundwater pH and the increases
      in DIC and dissolved CO2 observed in the pulselike CO2-release tests were caused
      by dissolution of CO2 whereas alkalinity was likely affected by carbonate
      dissolution. 

PMID- 25383790
TI  - Quantitative proteome analyses identify PrfA-responsive proteins and
      phosphoproteins in Listeria monocytogenes.
AB  - Protein phosphorylation is a major mechanism of signal transduction in bacteria.
      Here, we analyzed the proteome and phosphoproteome of a wild-type strain of the
      food-borne pathogen Listeria monocytogenes that was grown in either chemically
      defined medium or rich medium containing glucose. We then compared these results
      with those obtained from an isogenic prfA* mutant that produced a constitutively
      active form of PrfA, the main transcriptional activator of virulence genes. In
      the prfA* mutant grown in rich medium, we identified 256 peptides that were
      phosphorylated on serine (S), threonine (T), or tyrosine (Y) residues, with a
      S/T/Y ratio of 155:75:12. Strikingly, we detected five novel phosphosites on the
      virulence protein ActA. This protein was known to be phosphorylated by a cellular
      kinase in the infected host, but phosphorylation by a listerial kinase had not
      previously been reported. Unexpectedly, SILAC experiments with the prfA* mutant
      grown in chemically defined medium revealed that, in addition to previously
      described PrfA-regulated proteins, several other proteins were significantly
      overproduced, among them were several proteins involved in purine biosynthesis.
      This work provides new information for our understanding of the correlation among
      protein phosphorylation, virulence mechanisms, and carbon metabolism. 

PMID- 25383792
TI  - Introduction to the special section on religion and spirituality in family life:
      pathways between relational spirituality, family relationships and personal well
      being.
AB  - This special section on faith and family life presents 5 studies that each offer
      novel insights into the complex web of linkages between a target family member's
      religious and/or spiritual (R/S) functioning and parental or family factors that
      may influence the target family member's psychological or R/S functioning. The
      outcome domain of interest is adolescent psychological functioning in the first
      three studies, parental stress in the fourth study, and the R/S functioning of
      adult children in the fifth study. In this introduction, we feature unique
      findings from each study. We then highlight 3 key conceptual issues that
      researchers need to recognize to continue to move forward rigorous research on
      specific roles that R/S can play in enhancing as well as undermining individual
      and family well-being.

PMID- 25383793
TI  - Income and children's behavioral functioning: a sequential mediation analysis.
AB  - Children from low-income households tend to exhibit higher levels of conduct
      problems and emotional problems, yet the pathways linking economic disadvantage
      to children's behavioral functioning are not well understood. This study uses
      data from the Early Steps Multisite (ESM) project (N = 731) to investigate
      associations between family income in early childhood and children's conduct
      problems and emotional problems in middle childhood. The study explores whether
      the associations from income to child conduct problems and emotional problems
      operate through maternal depressive symptoms and 3 family risk factors in early
      childhood-harsh parenting, parenting hassles, and chaos in the home environment.
      Results of a sequential mediation model revealed significant indirect effects of
      family income on children's conduct problems operating through maternal
      depressive symptoms and parenting hassles and indirect effects of family income
      on children's emotional problems operating through maternal depressive symptoms,
      chaos in the home environment, and parenting hassles. Implications of these
      findings for understanding processes through which income influences child
      functioning are discussed.

PMID- 25383794
TI  - Income, neighborhood stressors, and harsh parenting: test of moderation by
      ethnicity, age, and gender.
AB  - Family and neighborhood influences related to low-income were examined to
      understand their association with harsh parenting among an ethnically diverse
      sample of families. Specifically, a path model linking household income to harsh
      parenting via neighborhood disorder, fear for safety, maternal depressive
      symptoms, and family conflict was evaluated using cross-sectional data from 2,132
      families with children ages 5-16 years from Chicago. The sample was 42% Mexican
      American, 41% African American, and 17% European American. Results provide
      support for a family process model where a lower income-to-needs ratio is
      associated with higher reports of neighborhood disorder, greater fear for safety,
      and more family conflict, which is in turn, associated with greater frequency of
      harsh parenting. Our tests for moderation by ethnicity/immigrant status, child
      gender, and child age (younger child vs. adolescent) indicate that although paths
      are similar for families of boys and girls, as well as for families of young
      children and adolescents, there are some differences by ethnic group.
      Specifically, we find the path from neighborhood disorder to fear for safety is
      stronger for Mexican American (United States born and immigrant) and European
      American families in comparison with African American families. We also find that
      the path from fear for safety to harsh parenting is significant for European
      American and African American families only. Possible reasons for such moderated
      effects are considered.

PMID- 25383795
TI  - Change in participant engagement during a family-based preventive intervention:
      ups and downs with time and tension.
AB  - The efficacy of preventive interventions is related to both the delivery of
      content and the uptake of that content. Although much research has focused on the
      quality of delivery, few studies have examined the factors that influence uptake.
      This study examines how and why participants' engagement-conceptualized as a
      dynamic process wherein participants interact with each other, the
      interventionists, and the intervention curriculum-changes over time. We apply
      growth curve models to repeated measures of engagement obtained from 252 families
      during a 7-week intervention trial. In the models, we examine (a) whether and how
      engagement changes over time, and the extent of between-person differences in
      change; and (b) how those changes and differences are related to chronic and
      session-specific aspects of family tension, while also controlling for
      differences across parent sex and 2 versions of the Strengthening Families
      Program: For Parents and Youth Ages 10-14 (SFP 10-14). Results show that, on
      average, engagement increased over time, linearly with some deceleration, with
      substantial differences in both level and rates of change. Higher in-session
      chronic family tension was related to lower initial levels of engagement but not
      rates of change. Sessions when families displayed more session-specific tension
      were characterized by different levels of engagement for parents, depending on
      their level of chronic tension. Overall, our results highlight the importance of
      considering engagement as a dynamic construct that changes over time in complex
      ways. Further understanding of the many factors that influence engagement can
      promote both better delivery and better uptake of intervention curriculum.

PMID- 25383796
TI  - Lost in the city: revisiting Milgram's experiment in the age of social networks.
AB  - As more and more users access social network services from smart devices with GPS
      receivers, the available amount of geo-tagged information makes repeating
      classical experiments possible on global scales and with unprecedented precision.
      Inspired by the original experiments of Milgram, we simulated message routing
      within a representative sub-graph of the network of Twitter users with about 6
      million geo-located nodes and 122 million edges. We picked pairs of users from
      two distant metropolitan areas and tried to find a route between them using local
      geographic information only; our method was to forward messages to a friend
      living closest to the target. We found that the examined network is navigable on
      large scales, but navigability breaks down at the city scale and the network
      becomes unnavigable on intra-city distances. This means that messages usually
      arrived to the close proximity of the target in only 3-6 steps, but only in about
      20% of the cases was it possible to find a route all the way to the recipient, in
      spite of the network being connected. This phenomenon is supported by the
      distribution of link lengths; on larger scales the distribution behaves
      approximately as P(d) ~ 1/d, which was found earlier by Kleinberg to allow
      efficient navigation, while on smaller scales, a fractal structure becomes
      apparent. The intra-city correlation dimension of the network was found to be D2
      = 1.25, less than the dimension D2 = 1.78 of the distribution of the population.

PMID- 25383797
TI  - Heat transfer analysis of MHD thin film flow of an unsteady second grade fluid
      past a vertical oscillating belt.
AB  - This article aims to study the thin film layer flowing on a vertical oscillating
      belt. The flow is considered to satisfy the constitutive equation of unsteady
      second grade fluid. The governing equation for velocity and temperature fields
      with subjected initial and boundary conditions are solved by two analytical
      techniques namely Adomian Decomposition Method (ADM) and Optimal Homotopy
      Asymptotic Method (OHAM). The comparisons of ADM and OHAM solutions for velocity
      and temperature fields are shown numerically and graphically for both the lift
      and drainage problems. It is found that both these solutions are identical. In
      order to understand the physical behavior of the embedded parameters such as
      Stock number, frequency parameter, magnetic parameter, Brinkman number and
      Prandtl number, the analytical results are plotted graphically and discussed. 

PMID- 25383798
TI  - Atomically thin heterostructures based on single-layer tungsten diselenide and
      graphene.
AB  - Heterogeneous engineering of two-dimensional layered materials, including
      metallic graphene and semiconducting transition metal dichalcogenides, presents
      an exciting opportunity to produce highly tunable electronic and optoelectronic
      systems. In order to engineer pristine layers and their interfaces, epitaxial
      growth of such heterostructures is required. We report the direct growth of
      crystalline, monolayer tungsten diselenide (WSe2) on epitaxial graphene (EG)
      grown from silicon carbide. Raman spectroscopy, photoluminescence, and scanning
      tunneling microscopy confirm high-quality WSe2 monolayers, whereas transmission
      electron microscopy shows an atomically sharp interface, and low energy electron
      diffraction confirms near perfect orientation between WSe2 and EG. Vertical
      transport measurements across the WSe2/EG heterostructure provides evidence that
      an additional barrier to carrier transport beyond the expected WSe2/EG band
      offset exists due to the interlayer gap, which is supported by theoretical local
      density of states (LDOS) calculations using self-consistent density functional
      theory (DFT) and nonequilibrium Green's function (NEGF). 

PMID- 25383799
TI  - The Tamiflu saga continues: will our conduct change after the publication of the
      latest systematic review on benefits and harms of oseltamivir?
AB  - In 2013, we wrote about the harm, waste and deception stemming from conducts
      adopted by the pharmaceutical industry, by concealing raw data and Clinical Study
      Reports (CSRs) from the regulator?s view when requesting the marketing patent. We
      described the case of Tamiflu (Roche), a drug that has been widely used in our
      population and profusely prescribed by physicians. Health authorities, entailing
      a great cost for the countries in the region, have also purchased it. In this
      editorial, we will show how the idea of using antivirals for prophylaxis and
      treatment of influenza took hold, starting from the first enthusiastic
      recommendations up to the systematic review published last month in the BMJ. 

PMID- 25383800
TI  - Cu(II)-Cu(I) synergistic cooperation to lead the alkyne C-H activation.
AB  - An efficient alkyne C-H activation and homocoupling procedure has been studied
      which indicates that a Cu(II)/Cu(I) synergistic cooperation might be involved. In
      situ Raman spectroscopy was employed to study kinetic behavior, drawing the
      conclusion that Cu(I) rather than Cu(II) participates in the rate-determining
      step. IR, EPR, and X-ray absorption spectroscopy evidence were provided for
      structural information, indicating that Cu(I) has a stronger interaction with
      alkyne than Cu(II) in the C-H activation step. Kinetics study showed Cu(II) plays
      a role as oxidant in C-C bond construction step, which was a fast step in the
      reaction. X-band EPR spectroscopy showed that the coordination environment of
      CuCl2(TMEDA) was affected by Cu(I). A putative mechanism with Cu(I)-Cu(II)
      synergistic cooperation procedure is proposed for the reaction. 

PMID- 25383804
TI  - A case of vasoproliferative retinal tumor complicated by neovascular glaucoma.
AB  - PURPOSE: To report a case of vasoproliferative retinal tumor complicated by
      neovascular glaucoma that showed remission after vitrectomy surgery to remove the
      tumor. METHODS: A 78-year-old man was referred to the hospital with a complaint
      of visual loss in his right eye. Corrected visual acuity was 0.5 in the right eye
      and 1.2 in the left eye. The right eye showed mild vitreous hemorrhage and an
      elevated lesion in the lower fundus. Fluorescein angiography demonstrated leakage
      from the tumor, and a 4-mm lesion of high density was seen on computed
      tomography, and we diagnosed it as retinal capillary hemangioma. In this case,
      von Hippel-Lindau disease was negative. During the course of the disease,
      peripheral anterior synechia and neovascularization was seen in the iris and
      angle, and vitreous surgery was enforced to remove the tumor because of increased
      intraocular pressure. The tumor was removed as almost one mass. Histologically,
      the tumor was composed of glial cells and small vessels proliferation. We
      diagnosed vasoproliferative retinal tumor. RESULTS: Seven months after surgery,
      the intraocular pressure stabilized, and neovascularization of the iris and angle
      disappeared. Visual acuity was 0.03 due to epiretinal membrane and optic atrophy.
      There were no signs of recurrence. CONCLUSION: The vitreous surgery is one of the
      effective treatment methods against vasoproliferative retinal tumor complicated
      by neovascular glaucoma.

PMID- 25383805
TI  - We would like to know in the case presented if there were any signs of anterior
      segment inflammation, as this was not mentioned.

PMID- 25383806
TI  - To the editor.

PMID- 25383807
TI  - Reactivation of ocular toxoplasmosis after pars plana vitrectomy.
AB  - PURPOSE: To report a case with reactivation of toxoplasma choroiretinitis after
      pars plana vitrectomy. PATIENTS AND METHODS: A 58-year-old female patient was
      diagnosed with secondary epiretinal membrane in her right eye. Bimanual 23-gauge
      pars plana vitrectomy and membrane peeling was performed. At first week
      postoperatively, visual acuity decreased; in slit-lamp examination, there were 3+
      cells in the anterior chamber with keratic precipitate. Fundoscopic examination
      revealed reactivation of chorioretinitis adjacent to the previous scar. RESULTS:
      The patient was diagnosed with reactivation of toxoplasma chorioretinitis and
      treated with oral trimethoprim-sulfamethoxazole, clindamycin and topical
      prednisolon acetate, and cyclopentolate drops for 5 weeks. Forty-eight hours
      after initiation of antibiotics, oral prednisone was added to the regimen and the
      dose was tapered to zero over the following 5 weeks. After 3 weeks of treatment,
      lesion was inactivated. CONCLUSION: Ocular toxoplasmosis reactivation may develop
      after pars plana vitrectomy. After intraocular surgery, reactivation of ocular
      toxoplasmosis should be considered in the follow-up.

PMID- 25383808
TI  - Unusual multifocal pigmented lesions of the uvea in a patient with ocular
      melanocytosis.
AB  - PURPOSE: To report findings of unusual multifocal pigmented lesions in a single
      patient with sector uveal melanocytosis. METHODS: Retrospective case report of an
      otherwise healthy 64-year-old man with unusual uveal pigmentation. Complete
      ocular examination, including slit-lamp biomicroscopy, ophthalmoscopy, optical
      coherence tomography, and ultrasound biomicroscopy, was performed. RESULTS: Slit
      lamp examination disclosed inferior sector pigmentation of the iris.
      Ophthalmoscopy showed multiple discrete, deeply pigmented, inferior choroidal
      lesions, and ultrasound biomicroscopy confirmed a small inferior ciliary body
      mass. The findings were consistent with sector uveal melanocytosis, believed to
      be the same as a diffuse melanocytoma. CONCLUSION: Melanocytoma is typically a
      unilateral, unifocal lesion that occurs on the optic disc but can be located
      anywhere in the uveal tract. This is a case of unusual pigmented uveal lesions,
      likely representing a variant of sector uveal melanocytosis or multiple diffuse
      uveal melanocytomas.

PMID- 25383809
TI  - Neovascularization of the optic disk and vitreous hemorrhage after immune
      recovery and treatment of cytomegalovirus retinitis in an HIV-positive patient.
AB  - PURPOSE: To report a case of neovascularization of the disk and vitreous
      hemorrhage associated with cytomegalovirus retinitis in an HIV-positive man on
      highly active antiretroviral therapy. METHODS: Clinical examination by fellowship
      trained retina specialist, including fundus photography and fluorescein
      angiography. RESULTS: A 44-year-old HIV-positive man with known history of
      cytomegalovirus retinitis subsequently developed neovascularization of the disk
      and vitreous hemorrhage after the initial treatment. This was treated with
      panretinal photocoagulation and responded well to treatment. CONCLUSION:
      Neovascularization of the disk and vitreous hemorrhage are rare but important
      sequelae of cytomegalovirus retinitis in the HIV-positive population.

PMID- 25383810
TI  - Autofluorescence and spectral domain OCT findings in Alport syndrome.
AB  - PURPOSE: The purpose of this study was to report novel autofluorescence and
      spectral domain optic coherence tomography findings in a case of Alport syndrome.
      METHODS: Case report and literature review. RESULTS: A 30-year-old woman with a
      history of Alport syndrome presented with a full-thickness macular hole in her
      right eye and evidence of vitreofoveal traction in her asymptomatic left eye.
      Both eyes had temporal macular thinning. She had anterior lenticonus and
      perimacular flecks characteristic of Alport syndrome. In addition, fundus
      autofluorescence revealed an interesting pattern of splotchy hypoautofluorescence
      in the periphery (in the absence of any peripheral retinopathy on examination),
      which has not been described previously. CONCLUSION: Macular hole in Alport
      syndrome results from basement membrane weakness and an abnormal vitreoretinal
      interface. Although this makes surgery in these cases challenging, careful
      separation of the posterior hyaloid and internal limiting membrane peeling with
      fluid gas exchange can lead to successful closure. Alport syndrome can also cause
      abnormalities in the retinal pigment epithelium/Bruch membrane leading to
      abnormal autofluorescence.

PMID- 25383811
TI  - Vogt-Koyanagi-Harada disease and fungal meningitis.
AB  - PURPOSE: To describe a patient who initially presented with features of Vogt
      Koyanagi-Harada disease and who eventually demonstrated symptoms of mycotic
      meningitis. METHODS: An 18-year-old immunocompetent boy showed a disseminated
      uveitis with patchy thickening of the posterior choroid. A clinical neurologic
      examination and a microbiological assessment revealed neck stiffness as well as
      pleocytosis, increased protein content, a decreased concentration of glucose and
      chloride, and cryptococcal fungi in the cerebrospinal fluid. It led to the
      diagnosis of cryptococcal meningitis. RESULTS: Antifungal therapy was initiated
      and given for 2 months. After bilateral retrobulbar injections of 2.5 mg of
      dexamethasone and 20 mg of triamcinolone acetonide, choroidal edema regressed and
      visual acuity increased from 0.4 to 1.0 at 3 weeks after start of therapy.
      Microbiological examination of cerebrospinal fluid samples taken 30 days later
      was unremarkable. Ophthalmoscopy showed some fine pigment clumping and
      depigmentation in the macula. CONCLUSION: According to the International
      Nomenclature Committee for Vogt-Koyanagi-Harada diagnosis, the patient was
      diagnosed with incomplete Vogt-Koyanagi-Harada because he had not suffered any
      ocular trauma, had not undergone ocular surgery, and presented with bilateral
      multifocal choroiditis accompanied by signs of meningitis without skin
      abnormalities. Because skin changes can occur months to years after the initial
      symptoms, the patient may eventually fulfill the criteria for complete Vogt
      Koyanagi-Harada disease.

PMID- 25383812
TI  - Pars plana vitrectomy with internal limiting membrane removal in type 2
      idiopathic macular telangiectasia.
AB  - PURPOSE: To report the anatomical and visual outcomes in a series of patients
      with type 2 idiopathic macular telangiectasia (mactel) and cystic foveal changes
      treated with pars plana vitrectomy and internal limiting membrane removal.
      METHODS: Five eyes of 3 patients with mactel were treated with 25-gauge
      sutureless transconjunctival pars plana vitrectomy and internal limiting membrane
      peeling. Complete clinical examination, including serial spectral-domain optical
      coherence tomography, was performed preoperatively and postoperatively. RESULTS:
      Two of 5 eyes had stable vision at 2-year follow-up with continued evidence of
      foveal cystic spaces on spectral-domain optical coherence tomography. Two eyes
      experienced significant visual improvement despite continued evidence of foveal
      anatomical disruption. One eye experienced slight visual decline and full
      thickness macular hole formation. CONCLUSION: Surgical intervention involving
      pars plana vitrectomy with internal limiting membrane peeling may be a treatment
      option for select cases of mactel. Pars plana vitrectomy does not seem to alter
      the underlying disease process in mactel but may stabilize visual decline or lead
      to improved vision in some patients.

PMID- 25383813
TI  - Spectral-domain optical coherence tomography and fundus autofluorescence findings
      in a case of laser pointer-induced maculopathy.
AB  - PURPOSE: To describe the spectral-domain optical coherence tomography and fundus
      autofluorescence findings in a case of laser pointer-induced maculopathy.
      METHODS: Observational case report of a patient with bilateral decreased visual
      acuity after exposure to a handheld green laser pointer. RESULTS: A 15-year-old
      boy presented with decreased vision after exposure to a green laser pointer.
      Fundoscopy revealed gray and yellowish round spots in the foveal area of both
      eyes. Fundus autofluorescence imaging revealed subtle changes of the normal
      background macular autofluorescence of the right eye, with hyperautofluorescence
      dots in the fovea of the left eye. Spectral-domain optical coherence tomography
      showed a variety of changes of the outer retina and retinal pigment epithelium,
      with disruption of the external limiting membrane, the photoreceptor ellipsoid
      zone of the inner segments, and the interdigitation zone in the foveal region in
      both eyes. Six months after laser exposure, fundoscopic examination showed
      persistent alterations at the level of the retinal pigment epithelium in the
      fovea in both eyes. Fundus autofluorescence revealed mild but persistent changes
      of the normal autofluorescent macular background in both eyes. Spectral-domain
      optical coherence tomography showed partial resolution of the outer retinal
      disruption noted on his initial visit with persistent, small foveal photoreceptor
      defects in both eyes. CONCLUSION: Laser pointer maculopathy may disturb the outer
      retinal architecture in a manner evident on spectral-domain optical coherence
      tomography and fundus autofluorescence, resulting in decreased visual acuity.
      Proper warnings should accompany these devices and access to them by minors
      should be limited.

PMID- 25383814
TI  - Macular branch retinal artery occlusion as the first manifestation of ocular
      toxoplasmosis.
AB  - BACKGROUND: Ocular toxoplasmosis can cause a variety of retinal vascular changes
      including branch retinal arterial occlusion, which is a rare complication of the
      disease. METHODS: An unusual toxoplasma chorioretinitis presenting a macular
      branch retinal arterial occlusion adjacent to the active chorioretinitis lesion
      is reported. RESULTS: The patient received an appropriate steroid and antibiotic
      treatment, and the retinitis lesion resolved over a 6-week period. At 2 months
      after diagnosis, visual acuity in her left eye was 20/30 and there was a
      hyperpigmented scar at the site where active retinitis had been observed.
      CONCLUSION: As this branch vascular obstruction may change the appearance of the
      fundus and obscure the initial inflammatory focus, ocular toxoplasmosis should be
      included in the differential diagnosis of branch retinal vascular occlusion
      associated with posterior uveitis, particularly in young patients.

PMID- 25383815
TI  - Acute retinal necrosis in a neonate.
AB  - PURPOSE: To report an unusual case of dizygotic twins, in whom one neonate
      developed acute retinal necrosis from herpes simplex virus (HSV) type 2. METHODS:
      Retrospective chart review. RESULTS: A 29-week-old premature infant from in vitro
      fertilization donor egg with negative maternal and fetal history for HSV-1 and
      HSV-2 developed vesiculopapular rash upon birth. Fundus examination revealed
      vitritis with retinal hemorrhages, suggestive of retinitis; the twin, however,
      had a normal funduscopic examination. A presumptive diagnosis of HSV infection
      was made, and the patient was started on intravenous acyclovir. Polymerase chain
      reaction of the anterior chamber fluid was positive for HSV-2; serology of both
      mother and child was HSV-2 IgG(+), IgM(-). Acute retinal necrosis was managed
      with 360 degrees  of bilateral peripheral laser cerclage. A subsequent
      rhegmatogenous retinal detachment in one eye was successfully treated with a
      scleral buckle. Retinal reattachment, macular pigmentary disturbances, and mild
      optic atrophy were noted at 6 months of follow-up. CONCLUSION: The authors report
      a case of isolated congenital acute retinal necrosis in an otherwise healthy
      neonate, and product of a dichorionic, diamniotic in vitro fertilization
      pregnancy. Clinicians should consider possible HSV transmission from in vitro
      fertilization donor egg in the differential diagnosis, despite the negative fetal
      and maternal histories for HSV infection.

PMID- 25383816
TI  - Sequential, acute noninfectious uveitis associated with separate intravitreal
      injections of bevacizumab and ranibizumab.
AB  - PURPOSE: To report the unique response of a patient with exudative age-related
      macular degeneration who developed sequential episodes of acute noninfectious
      uveitis following separate intravitreal injections of bevacizumab and
      ranibizumab. METHODS: Retrospective interventional case report. Chart review.
      RESULTS: A 73-year-old white woman, who received monthly intravitreal bevacizumab
      injections for exudative age-related macular degeneration in the right eye,
      developed decreased vision 4 days after her last injection. She had trace
      anterior chamber cells and 1+ vitritis, consistent with a bevacizumab-associated
      uveitis. The patient improved on topical steroids and cycloplegics. Subsequently,
      her exudative age-related macular degeneration was treated with monthly
      ranibizumab injections. Optical coherence tomography demonstrated persistent
      subretinal fluid despite treatment. Seven days after her 11th ranibizumab
      injection, she developed sudden decreased vision, 2+ anterior chamber cell, and
      4+ vitritis. Presumptive treatment for an exogenous bacterial endophthalmitis was
      given after a vitreous biopsy was performed, which demonstrated severe sterile
      infiltrates that were culture negative. All injections were stopped. Three months
      later, the subretinal fluid had disappeared, the vitritis has nearly resolved,
      but some intraretinal fluid persisted. CONCLUSION: Acute noninfectious uveitis, a
      known risk following injection with either bevacizumab or ranibizumab, may
      develop sequentially in the same patient, suggesting the possibility of cross
      sensitivity. Additionally, spontaneous anatomical improvement after uveitis from
      antibody-based vascular endothelial growth factor inhibition implies a
      suppressive immunomodulatory effect on vascular permeability or choroidal
      neovascularization. The availability of agents with alternative molecular
      structures, such as aflibercept, may permit additional insights into the complex
      relationship between choroidal neovascularization, vitritis, and innate and other
      immunologic processes.

PMID- 25383817
TI  - Listeria monocytogenes panophthalmitis: a novel strain follows a virulent course.
AB  - PURPOSE: To describe the findings and clinical course of a case of Listeria
      endophthalmitis as it progressed to panophthalmitis despite vitrectomy and
      intravitreal and systemic antibiotic therapy. METHODS: A case report of Listeria
      endophthalmitis progressing to panophthalmitis with a brief retrospective review
      of the literature pertaining to Listeria-related eye infections and endogenous
      endophthalmitis. RESULTS: A 70-year-old man presented with fulminant,
      hypertensive endophthalmitis and underwent pars plana vitrectomy, vitreous tap
      for Gram stain and culture, with intravitreal antibiotic injection and systemic
      intravenous antibiotic therapy, given the concern for an endogenous source.
      Despite this treatment, the patient progressed to no light perception vision with
      progressive orbital inflammatory signs. He then required enucleation with
      pathology, demonstrating an acute necrotizing panophthalmitis. DISCUSSION: This
      case demonstrates the importance of a high index of suspicion for endophthalmitis
      in the setting of progressive uveitis despite titration of topical corticosteroid
      therapy while describing the preferred management and antibiotic regimen for
      patients with Listeria-related infections. Previous reported cases of Listeria
      endophthalmitis characteristically present as a hypertensive endophthalmitis with
      pigment dispersion and a dark hypopyon. If endophthalmitis is suspected, an
      anterior chamber paracentesis with Gram stain and culture can aid in earlier
      diagnosis, thus allowing for prompt, targeted therapy and improved outcomes.

PMID- 25383818
TI  - Branch retinal artery occlusion after internal carotid artery angioplasty and
      stenting.
AB  - PURPOSE: A 67-year-old man with an embolic branch retinal artery occlusion
      occurring as a complication of internal carotid artery stenting, despite the use
      of a distal filter cerebral protection device was reported. METHODS:
      Observational case report. One patient case is included in this case report.
      RESULTS: The patient developed a branch retinal arterial occlusion with visible
      emboli 24 hours after a carotid angioplasty and stenting procedure and was found
      to have multiple anastomoses between the external carotid artery and ophthalmic
      artery as a result of carotid stenosis. He required a second, emergent
      angioplastic procedure. CONCLUSION: External carotid-ophthalmic arterial
      anastomoses can act as a pathway for emboli to travel from the internal carotid
      artery to the retinal circulation, resulting in retinal arterial occlusions,
      despite the use of cerebral protective devices. Ophthalmologists and
      interventional radiologists should be aware of these factors, especially as the
      number of percutaneous carotid artery stenting procedures continues to increase.

PMID- 25383819
TI  - Bilateral retinal pigment epithelium tears in acute Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To report an original case of retinal pigment epithelial (RPE) tears in
      acute Vogt-Koyanagi-Haradadisease. METHODS: Observational case report of a
      patient who presented with RPE tears in acute Vogt-Koyanagi-Harada disease, who
      underwent clinical examination, fluorescein and infracyanine green angiographies,
      and optical coherence tomography evaluation. RESULTS: A 42-year-old woman
      presented with bilateral serous retinal detachment related to Vogt-Koyanagi
      Harada disease. Eight days after high-dose systemic corticosteroids, she
      developed bilateral RPE tears. At the 15-month follow-up, visual acuity was 20/20
      in both eyes. CONCLUSION: The RPE tears are rarely observed in acute Vogt
      Koyanagi-Harada disease. The RPE tears were likely caused by acute inflammation
      of the choroidal stroma.

PMID- 25383820
TI  - Epiretinal deposits post cataract extraction.
AB  - PURPOSE: To report two unusual cases of epiretinal deposit post cataract surgery.
      METHODS: Retrospective identification of an unusual complication in patients who
      had cataract extraction recently with intraoperative complications. RESULTS: Two
      patients were identified with epiretinal deposits after cataract extraction where
      the posterior capsule barrier was breached. Inflammation was limited to the
      posterior segment, and investigative workup for infective causes was negative. No
      intraocular antibiotics had been used. In both the cases, hydroxypropyl
      methylcellulose was used as the viscoelastic substance. CONCLUSION: The authors
      report rare posterior segment toxicity in cataract surgeries complicated with
      intraoperative breach of posterior capsule barrier and hydroxypropyl
      methylcellulose use.

PMID- 25383821
TI  - Bilateral nanophthalmic uveal effusion syndrome: clinical presentation and
      surgical management.
AB  - PURPOSE: To describe the clinical presentation and surgical management of
      bilateral uveal effusion syndrome in a type 1 diabetic patient with
      nanophthalmos. METHODS: A 38-year-old man presented with decreased visual acuity.
      Fundus examination revealed exudative retinal detachment and choroidal folding.
      Ultrasound examination confirmed thickened sclera, choroidal effusion, and
      nanophthalmos. Partial thickness scleral windows and subscleral sclerectomy were
      performed. The patient returned 2 years postoperatively with the same
      presentation in the contralateral eye. RESULTS: After subscleral sclerectomy,
      intraocular pressure remained stable and the patient recovered premorbid vision
      in both eyes. At 4 years of follow-up, the patient's vision had remained stable
      without the need for further treatment. CONCLUSION: The association of uveal
      effusion syndrome with diabetes and other autoimmune disorders is unclear,
      warranting further research. Uveal effusion syndrome can be managed effectively
      by partial thickness scleral windows and sclerectomy with improvement and
      maintenance of visual acuity.

PMID- 25383822
TI  - Sequential surgical repair of a macular hole-related retinal detachment in a
      hyperopic patient.
AB  - PURPOSE: To report a case of macular hole-related retinal detachment in a
      hyperopic patient and a sequential surgical approach to repair. METHODS: Case
      report. PATIENTS: A single patient with acute macular hole-related retinal
      detachment. CONCLUSION: Retinal detachment secondary to macular hole typically
      occurs in highly myopic patients and is rare in patients with hypermetropia.
      Surgical repair may involve a combined or sequential approach to close the
      macular hole.

PMID- 25383823
TI  - Purtscher-like retinopathy associated with pemphigus vulgaris.
AB  - PURPOSE: To report a case of Purtscher-like retinopathy associated with pemphigus
      vulgaris. METHOD: Case report of a 25-year-old Hispanic male who was referred for
      sudden and severe reduction of vision from his right eye shortly after an
      exacerbation of pemphigus vulgaris. RESULTS: Fundus examination of the right eye
      revealed severe macular edema, nerve fiber layer infarcts, flame-shaped
      hemorrhages, and venous dilation. Fluorescein angiography and optical coherence
      tomography findings of flecken, ischemia with subsequent nerve fiber layer
      atrophy, and capillary leakage were consistent with Purtscher-like retinopathy.
      The patient was treated with 5 consecutive monthly intravitreal injections of 0.5
      mg of ranibizumab. Visual acuity improved with resolution of macular edema, and
      the patient was started on systemic mycophenolate mofetil. Continued ocular
      stability was achieved with 11 subsequent intravitreal injections over the
      following 2 years. CONCLUSION: Purtscher-like retinopathy may have been
      associated with pemphigus vulgaris through a complement activation process that
      is previously undescribed. Retinal findings were successfully mitigated with the
      use of intravitreal anti-vascular endothelial growth factor therapy.

PMID- 25383824
TI  - Macular pits and scleral dehiscence in highly myopic eyes with macular
      chorioretinal atrophy.
AB  - BACKGROUND: In highly myopic eyes, it is possible to observe the entire thickness
      of the sclera using swept-source optical coherence tomography. The peculiar
      scleral alterations observed using swept-source optical coherence tomography
      within the area of macular chorioretinal atrophy were reported. METHODS: The area
      of macular chorioretinal atrophy was scanned by swept-source optical coherence
      tomography in two patients with pathologic myopia. RESULTS: In one of the two
      patients, three pitlike clefts were observed within the area of the atrophy. The
      deepest pit was 715 MUm in depth from its opening. In the other patient, the
      sclera seemed to dehisce within the area of macular atrophy. In the adjacent
      sections of the scleral dehiscence, choroidal thickening was observed.
      CONCLUSION: These suggest that in the area of macular chorioretinal atrophy, the
      scleral curvature could be severely altered. The area of chorioretinal atrophy
      could expand more than the surrounding area due to a lack of RPE, Bruch membrane,
      and choriocapillaris.

PMID- 25383825
TI  - Presumed sympathetic ophthalmia after scleral buckling surgery.
AB  - PURPOSE: To report an unusual case of sympathetic ophthalmia after successful
      scleral buckling surgery. METHODS: The authors reported the clinical
      manifestation, ocular and systemic workup, and outcome of a 23-year-old woman who
      presented with reduced vision 3 weeks after successful scleral buckling surgery.
      RESULTS: Slit-lamp examination showed a mild anterior chamber and vitreous
      reaction. Fundus examination showed extensive serous retinal detachment in both
      eyes. Systemic workup was negative for extraocular disease. The patient was
      treated with intensive systemic steroid and azathioprine. The inflammation was
      controlled and serous detachment resolved. CONCLUSION: Sympathetic ophthalmia can
      occur after successful scleral buckling surgery.

PMID- 25383826
TI  - Retinal vascular tortuosity in DiGeorge syndrome complicated by solar
      retinopathy.
AB  - PURPOSE: To report a case of vascular tortuosity associated with DiGeorge
      syndrome that was complicated by solar retinopathy. METHODS: Case report and
      literature review. RESULTS: A 56-year-old woman with DiGeorge syndrome with
      secondary schizophrenia and developmental delay presented with decreased vision
      that was worse in her left eye. Ocular examination revealed bilateral retinal
      vascular tortuosity involving both the arteries and veins. Both eyes had an
      abnormal foveal light reflex with a central yellowish hue, which was more
      pronounced in the left eye. Optical coherence tomography showed disruption of the
      photoreceptor inner segment-outer segment junction and retinal pigment epithelium
      centrally, which was also more prominent in the left eye. CONCLUSION: DiGeorge
      syndrome is associated with retinal vascular tortuosity in a large percentage of
      patients. The patient's decreased vision is likely caused by solar retinopathy
      (prolonged sun gazing as a result of the secondary schizophrenia and
      developmental delay).

PMID- 25383827
TI  - Curvularia lunata endophthalmitis after penetrating ocular trauma.
AB  - PURPOSE: To report a case of Curvularia lunata endophthalmitis that responded to
      amphotericin B and itraconazole METHODS: Observational case report of one patient
      with C. lunata endophthalmitis after penetrating ocular injury with vegetable
      material. RESULTS: One young adult male patient presented with visual loss after
      penetrating ocular trauma with vegetable material. Biomicroscopy revealed
      keratitis and secondary endophthalmitis. Vitreous cultures after vitrectomy were
      positive for C. lunata and Staphylococcus epidermidis. Patient responded well to
      intravitreal amphotericin B and moxifloxacin. CONCLUSION: Fungal endophthalmitis
      should be suspected after trauma with vegetable material. Curvularia lunata may
      produce endophthalmitis and keratitis. Amphotericin B and itraconazole should be
      considered suitable agents for its treatment.

PMID- 25383828
TI  - Immunogammopathy maculopathy associated with Waldenstrom macroglobulinemia is
      refractory to conventional interventions for macular edema.
AB  - PURPOSE: To describe immunogammopathy maculopathy in the setting of Waldenstrom
      macroglobulinemia and its lack of response to ocular treatment. METHODS: Case
      report of a 65-year-old male patient who presented with a 4-month history of
      progressive vision loss in the left eye. RESULTS: Initial ophthalmic examination
      showed bilateral central retinal vein occlusion with macular edema, including
      serous macular detachment in the left eye. Serum protein electrophoresis revealed
      elevated IgM levels, leading to a diagnosis of Waldenstrom macroglobulinemia. The
      patient underwent plasmapheresis and systemic chemotherapy with improvement of
      hyperviscosity retinopathy. However, the macular detachment and edema in the left
      eye persisted despite repeated intravitreal injections of bevacizumab. Panretinal
      photocoagulation and intravitreal corticosteroid treatment were also unsuccessful
      in reversing the maculopathy. A diagnosis of immunogammopathy maculopathy was
      made, and partial improvement was seen over time after the treatment of
      Waldenstrom macroglobulinemia. CONCLUSION: In the setting of systemic
      immunogammopathy, conventional treatments for macular edema, including
      intravitreal anti-vascular endothelial growth factor agents and corticosteroids,
      may be ineffective. Ocular involvement responds to systemic chemotherapy and
      plasmapheresis directed against the underlying hematologic malignancy, although
      this response may be slow and incomplete.

PMID- 25383829
TI  - ND-yag laser arteriotomy for central retinal artery occlusion.
AB  - PURPOSE: To report a case of central retinal artery occlusion treated with Nd-YAG
      arteriotomy with successful outcome. METHODS: Interventional case report of a 61
      year-old man with central retinal artery occlusion who underwent an arteriotomy
      with embolectomy/embolysis with Nd-YAG laser. RESULTS: Best-corrected visual
      acuity improved to 9/200 immediately and 20/200 one day after the procedure. Two
      months later, the patient underwent pars plana vitrectomy for dispersed,
      nonclearing vitreous hemorrhage. Three months later, the patient had cataract
      surgery. Visual field significantly improved centrally at 5 months after Nd-YAG
      laser procedure. The final visual acuity was 20/40 at 15 months after the
      procedure. CONCLUSION: Nd-YAG laser may be beneficial in selected cases of
      retinal artery occlusion by enhancing the restoration of blood flow in the
      retinal vessels.

PMID- 25383830
TI  - Iatrogenic subfoveal diamond particle after macular hole repair surgery.
AB  - PURPOSE: To discuss surgical options and visual outcome when faced with a diamond
      intraoperative foreign body during macular hole surgery. METHODS: Case study of
      an iatrogenic in-the-macular-hole diamond particle noted during macular hole
      surgery. No attempt to retrieve the diamond from the macular hole was made during
      surgery. PATIENT: Forty-seven-year-old female patient with a 483-MUm macular
      hole. RESULTS: The patient's macular hole closed over the diamond particle,
      making it subfoveal. The visual acuity improved from 20/120 to 20/40 with
      resolution of metamorphopsia. CONCLUSION: It is likely that the inert nature and
      small size of diamond particles do not significantly affect visual acuity or hole
      closure and do not cause retinal toxicity. The authors discourage aggressive
      attempts to remove such particles during surgery.

PMID- 25383831
TI  - Bilateral choroidal tumors consistent with metastatic malignant paraganglioma.
AB  - PURPOSE: To report a patient with bilateral choroidal metastasis from a malignant
      paraganglioma. METHODS: Clinicopathologic case report and literature review.
      RESULTS: A 68-year-old woman presented with bilateral amelanotic focal choroidal
      lesions. A thorough systemic work-up for a primary cancer revealed a
      paraganglioma (extraadrenal pheochromocytoma) and a pheochromocytoma of the left
      adrenal gland. Fine-needle aspiration biopsy of the choroidal lesion was
      consistent with metastatic paraganglioma. CONCLUSION: Metastatic paraganglioma,
      although rare, has the ability to metastasize to the choroid.

PMID- 25383832
TI  - A case of central serous chorioretinopathy occurring after gamma-hydroxybutyric
      acid (liquid ecstasy) ingestion.
AB  - PURPOSE: To describe a patient with acute central serous chorioretinopathy after
      use of gamma-hydroxybutyric acid (GHB), also known as "liquid ecstasy." METHODS:
      Observational case report of a patient who developed central serous
      chorioretinopathy a day after use of GHB at a party. RESULTS: A young adult male
      patient presented at the department complaining of non-improving acute onset of
      vision loss in the left eye after use of GHB at a party 3 weeks before. Fundus
      examination, optical coherence tomography, and fluorescein angiography revealed a
      dome-shaped retinal elevation centered to the macula of the left eye, suggesting
      the diagnosis of central serous chorioretinopathy. Spontaneous subretinal fluid
      resolution with improvement of vision was observed a month later. CONCLUSION:
      gamma-hydroxybutyric acid has been reported to induce an acute increase in
      cortisol secretion after its administration. In addition, a case of Cushing
      syndrome after chronic abuse of GHB has been described. The acutely increased
      cortisol levels, induced by GHB, might have been the cause of central serous
      chorioretinopathy in the patient.

PMID- 25383833
TI  - Spectral domain optical coherence tomography demonstrates interconnected orbital
      cyst and chorioretinal coloboma in an adult.
AB  - PURPOSE: To report an orbital cyst underlying a chorioretinal coloboma in an
      otherwise normal eye, detected by spectral domain optical coherence tomography
      imaging. To the authors' knowledge, this is the first case of a chorioretinal
      colobomatous cyst in the normal eye to be reported. METHODS: A descriptive case
      report of a patient with a chorioretinal coloboma with an underlying orbital
      cyst. RESULTS: A 59-year-old woman presented with a floater affecting her left
      visual field. Fundoscopy revealed a pale lesion inferotemporal to fixation at the
      left macula. Spectral domain optical coherence tomography revealed a
      retinochoroidal coloboma with an associated scleral hole. Enhanced depth imaging
      spectral domain optical coherence tomography revealed an underlying orbital
      colobomatous cyst. CONCLUSION: To the authors' knowledge, this is the first case
      of a healthy adult with a retinochoroidal colobomatous cyst without
      microphthalmos. The authors encourage optical coherence tomography of any
      suspected colobomas to exclude similar pathology.

PMID- 25383834
TI  - Successful resolution of endophytic optic disk hemangioma by photodynamic
      therapy.
AB  - PURPOSE: To report the successful resolution of an endophytic optic disk
      hemangioma (ODH) by photodynamic therapy. METHODS: Case report. RESULTS: A 48
      year-old man presented with endophytic ODH in his right eye. His best-corrected
      visual acuity was 1.2 in the right eye, but there was a serous retinal detachment
      with exudations extending from the tumor. Two intravitreal injections of
      bevacizumab were given with an interval of 6 months; however, the size of the ODH
      continued to increase and the best-corrected visual acuity decreased from 1.2 to
      0.2. One year after the last injection of bevacizumab, 2 sessions of photodynamic
      therapy were performed with an interval of 4 months. The follow-up examination 2
      years after the second photodynamic therapy showed that the ODH was reduced in
      size and its activity was low. The best-corrected visual acuity remained at 0.3.
      CONCLUSION: The findings indicate that photodynamic therapy can be an effective
      therapy for eyes with an ODH.

PMID- 25383835
TI  - Frosted branch angiitis in an octogenarian with infective endocarditis.
AB  - PURPOSE: To present the difficulties in diagnosing frosted branch angiitis (FBA)
      in an elderly person, and to present the likely immunogenic association of FBA
      with alpha-hemolytic streptococci. METHODS: Thorough review of the medical
      records of an 80-year-old white man diagnosed with FBA. Patient consent was
      obtained before the writing of this article. RESULTS: Our patient presented with
      1 week of decreasing vision and floaters in his right eye and 3 days of floaters
      in his left eye. Significant medical history included a prosthetic mitral valve.
      Notable features on examination were bilateral retinal vascular sheathing, with
      retinal edema and hemorrhage. Preliminary investigations-including a
      transoesophageal echocardiogram-did not reveal intraocular or systemic infection,
      autoimmune disease, or underlying malignancy. Idiopathic FBA was unlikely given
      that the majority of cases had been documented in middle-aged Japanese
      populations. Thus, we chose to treat our patient empirically for common causes of
      retinal vasculitis such as viral retinitis. Interestingly, 2 weeks after the
      diagnosis of FBA, our patient became febrile. He was subsequently diagnosed with
      infective endocarditis and commenced on intravenous vancomycin (penicillin
      allergy). Review of his transoesophageal echocardiogram found an oscillating
      lesion that had been initially missed. Therefore, it is likely that our patient
      had blood culture-negative endocarditis at the time of presentation. This was
      further supported by the regression of his ocular disease with intravenous
      vancomycin. CONCLUSION: We hypothesize that our patient developed FBA as an
      immunogenic response to Streptococcus viridans and Streptococcus oralis
      infection. Previous associations between streptococci and FBA have been made.
      Notably, beta-hemolytic streptococcal antigens are known to cross-react with
      retinal antigens. However, the implicated pathogens in our patient were alpha
      hemolytic. Alpha-hemolytic streptococcal endophthalmitis has been linked to
      frosted branch response before, but it has never been associated with FBA through
      an immunogenic pathway. Therefore, it is important to note that idiopathic FBA
      can be associated with infective endocarditis and alpha-hemolytic streptococcal
      infections. Furthermore, FBA in elderly patients needs thorough evaluation to
      rule out systemic causes.

PMID- 25383836
TI  - Enhanced depth imaging optical coherence tomography features in a young case of
      primary hyperoxaluria Type 1.
AB  - PURPOSE: To describe the enhanced depth imaging optical coherence tomography
      findings in a very young case of Type 1 primary hyperoxaluria. METHODS:
      Observational case report of a young patient who underwent clinical examination
      and enhanced depth imaging optical coherence tomography evaluation. RESULTS: A 4
      year-old boy with a history of Type 1 primary hyperoxaluria and resulting chronic
      renal failure was referred to us for ophthalmologic examination. There were no
      ocular symptoms when he was referred to us. Fundus examination showed deposition
      of calcium oxalate crystals at the posterior pole located symmetrically in both
      eyes. Enhanced depth imaging optical coherence tomography evaluation revealed
      hyperreflective structures, localized under the photoreceptor inner segment/outer
      segment junction, and over the retinal pigment epithelium, consistent with
      deposition of oxalate crystals. There were no oxalate crystals in the superficial
      retinal layers, and we observed no evidence of deposition of oxalate crystals in
      choroid with enhanced depth imaging optical coherence tomography. CONCLUSION: We
      could not demonstrate any oxalate deposits in the choroid with enhanced depth
      imaging optical coherence tomography in this young case of primary hyperoxaluria
      Type 1. This may be related to the young age of our patient, and the amounts of
      the crystalline deposition may increase in the years ahead.

PMID- 25383837
TI  - Spectral domain optical coherence tomography-guided laser treatment of central
      serous chorioretinopathy in a pregnant woman.
AB  - PURPOSE: To report a case of central serous chorioretinopathy treated with focal
      laser photocoagulation guided by spectral domain optical coherence tomography (SD
      OCT) without fluorescein angiography. METHODS: In this interventional case
      report, a 27-year-old pregnant lady with central serous chorioretinopathy was
      evaluated with fundus photography and SD-OCT. She was treated with focal laser
      photocoagulation to the area of micro rip on the summit of pigment epithelial
      detachment identified by SD-OCT. RESULTS: Successful treatment of serous macular
      detachment using SD-OCT in a pregnant lady. CONCLUSION: We report a case of
      central serous chorioretinopathy evaluated and treated successfully with SD-OCT
      without the use of fluorescein angiography.

PMID- 25383838
TI  - Endogenous endophthalmitis due to clinically vancomycin-resistant Staphylococcus
      aureus.
AB  - PURPOSE: To report a case of clinically vancomycin-resistant Staphylococcus
      aureus endophthalmitis. METHODS: This is an observational case report of a
      patient referred for decreased vision during an admission for methicillin
      resistant S. aureus bacteremia. RESULTS: A 48-year-old woman with methicillin
      resistant S. aureus bacteremia presented with decreased vision in one eye. Best
      corrected visual acuity at presentation was 20/25 in the right eye and hand
      motion in the left eye. Biomicroscopic examination revealed evidence of
      endophthalmitis in both eyes. After a period of deterioration despite treatment
      with intravenous and intravitreal vancomycin and intravitreal ceftazidime-20/200
      in the right eye and light perception in the left eye, an alternative treatment
      regimen with intravenous daptomycin and intravitreal clindamycin and amikacin led
      to clinical improvement in both eyes, with quiescence of anterior chamber cell
      and vitritis. Best-corrected visual acuity at 3 weeks of follow-up had improved
      to 20/40 in the right eye and remained light perception in the left eye.
      CONCLUSION: In cases of endogenous endophthalmitis secondary to methicillin
      resistant S. aureus not responsive to intravenous and intravitreal vancomycin,
      particularly with borderline sensitivities, consideration to clinical resistance
      should be entertained.

PMID- 25383839
TI  - Endoresection of a high equatorial choroidal melanoma.
AB  - PURPOSE: To describe previously unreported endoresection of a high equatorial
      choroidal melanoma. METHODS: Surgical case report imaged with wide-angle
      retinography and angiography, ecography, optical coherence tomography, and a
      short video of surgical procedure. RESULTS: The authors describe a 9.68-mm thick
      mushroom-shaped equatorial melanoma, which was successfully treated by
      endoresection. A wide-field lens and scleral indentation allowed complete tumor
      removal by the vitrectomy probe. Liquid perfluorocarbon stabilized the retina,
      therefore laser endophotocoagulation was applied to tumor margins and the scleral
      bed. Silicone oil was left as a tamponade, and a ruthenium-106 plaque for
      radiation therapy was sutured to the episclera. Eleven months after endoresection
      surgery, there were no signs of systemic or local recurrences. CONCLUSION:
      Endoresection of an equatorial choroidal melanoma was shown to be a safe
      technique in this patient, allowing the preservation of anatomy and function of
      the eye. It should be considered as an option for the treatment of large
      equatorial choroidal melanomas.

PMID- 25383840
TI  - Bilateral diffuse uveal melanocytic proliferation with good clinical response to
      plasmapheresis and treatment of the primary tumor.
AB  - PURPOSE: To report successful treatment of bilateral diffuse uveal melanocytic
      proliferation. METHODS: Case report of a patient with clinical diagnosis of
      bilateral diffuse uveal melanocytic proliferation, imaged with fluorescein
      angiography and spectral domain optical coherence tomography, and with follow-up
      data after treatment with plasmapheresis, radiation, and chemotherapy. RESULTS: A
      67-year-old white man presented with a history of bilateral rapidly declining
      vision. The ophthalmoscopic examination, fluorescein angiography, and optical
      coherence tomography showed in both eyes an exudative retinal detachment and
      subretinal lesions highly suggestive for bilateral diffuse uveal melanocytic
      proliferation. Further investigation demonstrated a large cell lung carcinoma.
      Subsequently, the patient was treated with plasmapheresis, radiation, and
      chemotherapy. In a few weeks, the exudative retinal detachments resolved with
      gain of vision, and the retina remained flat during the 5-month follow-up.
      CONCLUSION: Plasmapheresis and treatment of the primary tumor are valuable
      treatment options for visually impaired patients with bilateral diffuse uveal
      melanocytic proliferation.

PMID- 25383841
TI  - Navigated laser (navilas) therapy for choroidal neovascular and hyperpermeability
      pathologies.
AB  - PURPOSE: To report the utility of navigated laser (NAVILAS) in the treatment of
      leaking areas in central serous chorioretinopathy and a feeder vessel in
      choroidal neovascular membrane. METHODS: Two patients with choroidal lesions were
      treated with NAVILAS. The first patient had central serous chorioretinopathy with
      visible leaking angiographic spots, and the second had choroidal neovascular
      membrane with a well-defined feeder vessel on angiography. Both patients
      underwent NAVILAS treatment. RESULTS: Both patients were successfully treated
      with resolution of clinical symptoms after a single session of NAVILAS. In
      addition, complete resolution of the subretinal fluid and leakage, and the
      subretinal blood and feeder vessel, were noted in the central serous
      chorioretinopathy and feeder vessel cases, respectively. CONCLUSION: NAVILAS may
      be of utility in targeting choroidal vascular pathologies with laser.

PMID- 25383842
TI  - Bilateral rhegmatogenous retinal detachment in spondyloepimetaphyseal dysplasia
      Strudwick type.
AB  - PURPOSE: To document the diagnosis and repair of bilateral retinal detachments in
      a child with spondyloepimetaphyseal dysplasia-Strudwick type, a rare autosomal
      dominant genetic disorder involving abnormal production of Type II collagen.
      METHODS: Case report. RESULTS: A 13-year-old patient diagnosed with
      spondyloepimetaphyseal dysplasia-Strudwick type presented with a localized
      superior temporal retinal detachment in the right eye and a 180 degrees  giant
      retinal tear with an associated macula-off retinal detachment in the left eye. He
      was highly myopic and had a visual acuity of 20/80 in the right eye and counting
      fingers in the left eye. He underwent a pars plana vitrectomy in the left eye and
      laser retinoplexy in the right eye, achieving complete reattachment and/or
      stabilization of both retinae, with a visual acuity of 20/60 in the right eye and
      20/100 in the left eye at 3 months postoperatively. CONCLUSION: Patients with
      spondyloepimetaphyseal dysplasia-Strudwick type may be at a higher risk of
      developing myopia, vitreoretinal degeneration, and a subsequent retinal
      detachment, although the scientific literature provides a loose association
      between these conditions. Critically, we propose a temporal association between
      retinal detachment and the onset of puberty in these patients and suggest that a
      dilated retinal screening examination should be scheduled at around the time of
      puberty for patients with spondyloepimetaphyseal dysplasia-Strudwick type to
      detect any asymptomatic retinal pathology.

PMID- 25383843
TI  - In-office use of the intrector for the removal of retained lens cortex.
AB  - PURPOSE: To report a case and technique for the removal of retained lens cortex
      material in an office-based procedure using a portable battery-powered vitrectomy
      system. METHODS: Case report. RESULTS: An 88-year-old man underwent uncomplicated
      office-based vitrectomy for the removal of retained lens material with good
      anatomical and visual outcomes. CONCLUSION: The authors report a case of the
      removal of retained cortex material using an office-based vitrector. Clinicians
      should be aware of this technique for selected patients.

PMID- 25383844
TI  - Use of intravitreal triamcinolone for the treatment of optic nerve edema in a
      patient with acute retinal necrosis: case report.
AB  - PURPOSE: To report the use of combined intravitreal triamcinolone and foscarnet
      therapy in a patient with active acute retinal necrosis. METHODS: Retrospective
      case report. A 40-year-old white woman with a history of ulcerative proctitis,
      intolerant to oral steroids, developed an aggressive case of acute retinal
      necrosis complicated by severe optic nerve edema resulting in 20/200 vision.
      RESULTS: Intravitreal foscarnet provided an initial improvement of the vitritis
      and retinitis; however, optic nerve edema and 20/200 vision persisted. After 2
      weeks, intravitreal triamcinolone was combined with the foscarnet dose. Four days
      later, the optic nerve edema had resolved, the vision returned to 20/40, and the
      herpetic infection remained controlled. Eight months later, the patient had not
      experienced a retinal detachment, and acuity was 20/20. Oral steroids are an
      accepted adjunct to antiviral therapy in acute retinal necrosis; however,
      combined intravitreal steroid and antiviral therapy has not been previously
      reported. After combined intravitreal therapy was attempted, the patient
      experienced a rapid resolution of symptoms without exacerbating her retinitis.
      CONCLUSION: In select patients, combined intravitreal triamcinolone and foscarnet
      may be effective in treating acute retinal necrosis and its inflammatory
      sequelae.

PMID- 25383845
TI  - Altering the clinical course of Sorsby fundus dystrophy with the use of anti
      vascular endothelial growth factor intraocular therapy.
AB  - PURPOSE: Sorsby fundus dystrophy is a rare hereditary condition causing choroidal
      neovascularization leading to vision loss. Previously, treatment was mostly
      unsuccessful. Here, we analyze the result of various treatments administered over
      the years. METHODS: Retrospective case-note review. PATIENTS: Three adults from a
      Spanish family with Sorsby fundus dystrophy showed a very varied course. The
      untreated case was blind at presentation. Administration of photodynamic therapy
      and intravitreal anti-vascular endothelial growth factor agents managed to modify
      the history of disease, more successfully with the latter. CONCLUSION: The
      intravitreal administration of anti-vascular endothelial growth factor agents
      seems to reduce the extent of scarring in Sorsby fundus dystrophy albeit without
      halting the episodic recurrences. This may lead to improved outcomes even when
      the visual acuity is compromised.

PMID- 25383846
TI  - Fundus autofluorescence and optical coherence tomography findings in thiamine
      responsive megaloblastic anemia.
AB  - BACKGROUND: To report ophthalmologic fundus autofluorescence and spectral domain
      optical coherence tomography findings in a patient with thiamine responsive
      megaloblastic anemia (TRMA). METHODS: A 13-year-old girl with genetically proven
      TRMA was ophthalmologically (visual acuity, funduscopy, perimetry,
      electroretinogram) followed up over >5 years. Fundus imaging also included
      autofluorescence and spectral domain optical coherence tomography. RESULTS:
      During a 5-year follow-up, visual acuity and visual field decreased, despite a
      special TRMA diet. Funduscopy revealed bull's eye appearance, whereas fundus
      autofluorescence showed central and peripheral hyperfluorescence and perifoveal
      hypofluorescence. Spectral domain optical coherence tomography revealed affected
      inner segment ellipsoid band and irregularities in the retinal pigment epithelium
      and choroidea. CONCLUSION: Autofluorescence and spectral domain optical coherence
      tomography findings in a patient with TRMA show retinitis pigmentosa-like retina,
      retinal pigment epithelium, and choroid alterations. These findings might
      progress even under special TRMA diet, indispensable to life. Ophthalmologist
      should consider TRMA in patients with deafness and ophthalmologic disorders.

PMID- 25383847
TI  - Long-term follow-up of photoreceptor loss and recovery after half-fluence
      photodynamic therapy for chronic central serous chorioretinopathy.
AB  - PURPOSE: To describe a case of chronic central serous chorioretinopathy with
      apparent transient, reversible loss of photoreceptor outer segments after half
      fluence photodynamic therapy (PDT). METHODS: The authors reviewed the clinical
      and imaging records over a 2-year period of a case of chronic central serous
      chorioretinopathy treated with PDT. RESULTS: A 58-year-old man with a 3-year
      history of blurry central vision in his right eye due to persistent subretinal
      fluid associated with central serous chorioretinopathy elected to undergo half
      fluence verteporfin PDT. Before treatment, visual acuity was 20/60, but 3 weeks
      after treatment, the patient returned complaining of significant worsening of
      vision to 20/200 and optical coherence tomography revealed resolution of
      subretinal fluid, but apparent loss of inner segment-outer segment band with
      preservation of the external limiting membrane. Twelve weeks after PDT, vision
      had recovered to 20/40 with reconstitution of inner segment-outer segment band
      under the fovea. The inner segment-outer segment band remained intact through the
      Month 22 follow-up visit. CONCLUSION: Severe visual loss can follow reduced
      fluence PDT for central serous chorioretinopathy. In this case, the mechanism of
      the loss appeared to be transient loss of the photoreceptor outer segments. The
      external limiting membrane remained intact in this case, a recovery of the outer
      segments with improvement in visual acuity was ultimately observed.

PMID- 25383848
TI  - Multifocal central serous chorioretinopathy with photoreceptor-retinal pigment
      epithelium diastasis in heritable pulmonary arterial hypertension.
AB  - PURPOSE: To report atypical central serous chorioretinopathy and choroidal
      thickening in a patient with heritable pulmonary arterial hypertension. METHODS:
      A 40-year-old man with heritable pulmonary arterial hypertension presented with
      blurred vision in his left eye and was followed up for 1 year with clinical
      examination, enhanced depth optical coherence tomography, fluorescein and
      indocyanine green angiography, and fundus photography. RESULTS: At presentation,
      atypical central serous chorioretinopathy with multiple retinal pigment
      epithelial detachments, a thick subfoveal choroid, and dilated choroidal vessels
      were seen in the patient's symptomatic left eye. After treatment for pulmonary
      hypertension, the serous detachments disappeared and choroidal thickness
      gradually decreased over a period of 4 weeks and remained unchanged at 13 months
      of follow-up. CONCLUSION: Central serous chorioretinopathy and choroidal
      thickening that responded to treatment of pulmonary arterial hypertension suggest
      a pathophysiological link between pulmonary arterial hypertension and central
      serous chorioretinopathy, perhaps mediated by choroidal venous stasis.

PMID- 25383849
TI  - Optical coherence tomography difference maps and average macular volume for
      geographic atrophy.
AB  - PURPOSE: To demonstrate the ability to monitor geographic atrophy (GA)
      volumetrically through all retinal layers with high-resolution optical coherence
      tomography difference maps and average macular volume. METHODS: Observational
      case report. RESULTS: Two patients diagnosed with GA were followed up for
      multiple years with consecutive high-resolution optical coherence tomography
      studies along with fundus photography and fluorescein angiography or fundus
      autofluorescence. Difference maps visually reflect macular thinning associated
      with expansion of GA witnessed on alternative studies. In addition, these maps
      show progressive macular thinning within previously delineated areas of GA.
      Average macular volume quantitatively demonstrates the decreasing volume
      associated with the expanding atrophy. CONCLUSION: Difference maps and average
      macular volume allow quantitative analysis of GA and may be a useful tool for
      patient care and clinical trials.

PMID- 25383850
TI  - Intravitreal triamcinolone acetonide treatment of tamoxifen maculopathy with
      associated cystoid macular edema.
AB  - PURPOSE: To report a case of severe tamoxifen-induced maculopathy with associated
      cystoid macular edema treated with intravitreal triamcinolone acetonide. METHODS:
      Case report. RESULTS: The patient presented with bilateral cystoid macular edema
      that persisted despite treatment, which included intravitreal bevacizumab
      injections. He received 7 triamcinolone injections in each eye over 20 months,
      resulting in the most recent best-corrected Snellen visual acuities of 20/40 in
      the right eye and 20/30 in the left eye. Complete resolution of the cystoid
      macular edema was achieved in each eye, but recurrent edema necessitated
      continued intermittent injections. Macular crystals persisted despite treatment
      but decreased since presentation. CONCLUSION: Intravitreal triamcinolone should
      be considered for treatment of tamoxifen-associated macular edema, especially if
      the condition responds poorly to anti-vascular endothelial growth factor
      treatments.

PMID- 25383851
TI  - Retinopathy in a patient with acute Epstein-Barr virus infection: follow-up
      analysis using spectral domain optical coherence tomography.
AB  - PURPOSE: To describe the clinical findings, diagnostics, and differential
      diagnosis in a patient with retinopathy in acute systemic Epstein-Barr virus
      (EBV) infection. METHODS: Description of the clinical course of the EBV
      retinopathy was based on the medical record, photographs, and visual fields of
      the patient. Retinal morphology was visualized using spectral domain optical
      coherence tomography (Heidelberg Engineering), and fluorescein angiography.
      Multiple serologic tests were performed to exclude different infectious agents. A
      30-year-old male patient presented with a focal scotoma in his right visual
      field. One week ago, he suffered from high fever, joint pain, neck stiffness, and
      hepatitis; 2 weeks later, he had returned from a trip to Malaysia. RESULTS:
      Visual acuity was 20/20 in both eyes. Fundoscopy showed a paravascular sharp
      edged white lesion with a corresponding crescent-shaped retinal nerve fiber
      defect. Serology revealed high titers for EBV immunoglobulin M (IgM), but no EBV
      immunoglobulin G (IgG), indicating an acute infectious mononucleosis. Other
      reasons for noninfectious or infectious retinochoroiditis including tropical
      microorganisms could be excluded serologically and by imaging. Treatment with
      systemic acyclovir and prednisolone acetate eye drops was initiated leading to
      recovery of systemic and ocular findings. CONCLUSION: Acute systemic EBV
      infection can affect the retina leading to focal thickening of the inner retinal
      layers because of focal microinfarction (cotton-wool spot) or focal infectious
      infiltration. Spectral domain optical coherence tomography is capable of
      detecting changes in retinal morphology in such cases.

PMID- 25383852
TI  - Efficacy of topical dorzolamide therapy for cystoid macular edema in a patient
      with MFRP-related nanophthalmos-retinitis pigmentosa-foveoschisis-optic disk
      drusen syndrome.
AB  - PURPOSE: Mutations in the MFRP (membrane-type frizzled-related protein) gene
      leads to an entity characterized by retinitis pigmentosa, nanophthalmos, optic
      disk drusen, and macular changes, originally described as foveoschisis. Despite
      the association of MFRP gene mutation and increase in macular thickness, no
      treatment modality has been described for cystoid macular edema related to this
      particular entity so far. METHODS: In this case report, a 52-year-old woman
      presented with nanophthalmos, optic disk drusen, retinitis pigmentosa, and
      increase in macular thickness. Genetic analysis revealed an MFRP gene mutation.
      The patient was treated with topical carbonic anhydrase inhibitors. RESULTS: A
      progressive decrease in macular thickness and cystic changes was observed during
      the 2-month course of topical carbonic anhydrase inhibitor treatment, and best
      corrected visual acuity improved from 20/100 to 20/50. Macular thickness remained
      stable after 6 months of follow-up. CONCLUSION: Cystoid macular edema is part of
      the macular changes noted in the MFRP mutation-related nanophthalmos-retinitis
      pigmentosa-foveoschisis-optic disk drusen, syndrome. Taking into account that
      resolution of cystoid macular edema in patients with retinitis pigmentosa may
      delay an irreversible decrease in visual acuity, treatment should be considered
      when cystic changes are suspected. Topical carbonic anhydrase inhibitor was
      effective in decreasing macular thickness and cystic changes in the patient
      reported.

PMID- 25383853
TI  - Choroid plexus in the eye: a case study.
AB  - PURPOSE: The purpose of this report is to describe a pediatric case of total
      retinal detachment (RD) with secondary glaucoma in the setting of posterior
      coloboma with the metaplastic retinal pigment epithelium showing abrupt
      transition to choroid plexus tissue. METHODS: Retrospective case report. RESULTS:
      A 3-month-old patient presented with leukocoria and enlarged right eye. She was
      found to have a funnel RD with anterior displacement of lens-iris diaphragm and
      secondary glaucoma. Orbital imaging ruled out retinoblastoma, and posterior
      coloboma was identified. Intraocular pressures remained significantly elevated
      despite maximal medical therapy on glaucoma drops and transscleral cycloablation,
      and the eye was enucleated for comfort. Histologic analysis confirmed
      neovascularization of the iris, total RD, and posterior coloboma with the
      associated metaplastic retinal pigment epithelium showing abrupt transition to
      choroid plexus tissue. CONCLUSION: This is the first reported case of choroid
      plexus in the human eye. A close association of choroid plexus with coloboma and
      RD raises possibility that this tissue may have functionally contributed to
      pathogenesis of RD by secreting cerebrospinal fluid within subretinal space.

PMID- 25383854
TI  - Recurrent hematuria in a patient with a previously undiagnosed transitional cell
      carcinoma of the right ureter after intravitreal bevacizumab (Avastin) injection:
      a case report.
AB  - PURPOSE: To report a case of gross hematuria in a patient with previously
      undiagnosed urothelial carcinoma of the right ureter after intravitreal
      bevacizumab (Avastin) injections. METHODS: In this case report and review of the
      literature, an 81-year-old woman presented with neovascular age-related macular
      degeneration in the left eye. She was treated with repeated intravitreal
      bevacizumab (Avastin) injections. After injection, she reported two episodes of
      gross hematuria. After disclosing this information to her ophthalmologist,
      bevacizumab treatment was suspended and the hematuria resolved. Urological
      evaluation revealed no abnormalities. Approximately 1 year later, treatment with
      intravitreal bevacizumab was resumed. After three injections, she again reported
      gross hematuria. Urological evaluation at that time revealed a high-grade
      urothelial carcinoma of the right ureter. A right nephroureterectomy was
      performed, and bevacizumab treatment was resumed. She did not report any
      subsequent episodes of hematuria. CONCLUSION: Hematuria has previously been
      reported with systemic administration of bevacizumab. However, hematuria after
      intravitreal injections of bevacizumab has not been reported and is most likely
      occurring as a result of the systemic absorption of the drug. Further
      investigation of the systemic effects of intravitreal bevacizumab may be
      warranted.

PMID- 25383855
TI  - Cancer-associated retinopathy with unusual retinal whitening.
AB  - PURPOSE: To describe the clinical characteristics and results of ocular and
      systemic testing in an atypical case of cancer-associated retinopathy. METHODS:
      This study is a retrospective case report of a female patient. RESULTS: Rapidly
      progressive visual loss, vitritis, white, ring- and coin-shaped retinal lesions,
      and panretinal optical coherence tomography thinning preceded the diagnosis of
      poorly differentiated cervical carcinoma with neuroendocrine features consistent
      with small-cell carcinoma. CONCLUSION: Cancer-associated retinopathy can present
      with ring- and coin-shaped retinal lesions, vitritis, and panretinal thinning.
      The presence of intraocular inflammation and retinal and choroidal vasculopathy
      may herald more rapid visual demise.

PMID- 25383856
TI  - Phthisis bulbi after lensectomy in retinopathy of prematurity eyes previously
      treated with laser photocoagulation.
AB  - PURPOSE: On rare occasions, patients with retinopathy of prematurity develop
      anterior segment ischemia after laser photocoagulation treatment. The purpose of
      this investigation was to describe the visual outcomes and the risk of phthisis
      bulbi after lensectomy in patients with history of retinopathy of prematurity
      laser photocoagulation and attached retinas at the time of lensectomy. METHODS: A
      retrospective case series including 3 patients who underwent diode laser
      photocoagulation for retinopathy of prematurity and developed unilateral anterior
      segment ischemia with subsequent cataract formation, and then phthisis bulbi
      after uncomplicated lensectomy. RESULTS: Three eyes became phthisical with total
      retinal detachment after uncomplicated cataract extraction. Signs of anterior
      segment ischemia were present in all 3 eyes before the cataract extraction,
      including shallow anterior chamber, corneal edema, iris atrophy, and posterior
      synechiae. Features of phthisis bulbi did not occur until after cataract
      extraction. CONCLUSION: Premature patients who require laser photocoagulation for
      retinopathy of prematurity and develop cataract presumably related to anterior
      segment ischemia are at high risk for poor visual outcomes. It is important to
      determine risks when performing lensectomy, especially because of the amblyogenic
      risk of cataract in an infant and the required visualization for retinal follow
      ups.

PMID- 25383857
TI  - Early detection of choroidal neovascularization facilitated with a home
      monitoring program in age-related macular degeneration.
AB  - PURPOSE: To describe clinical and imaging findings in two eyes with new onset
      subtle neovascular age-related macular degeneration that was detected by the
      regular use of a home monitoring device based on preferential hyperacuity visual
      field testing. METHODS: Interventional case report. RESULTS: Case 1, an 82-year
      old man with the intermediate stage of age-related macular degeneration in both
      eyes, had been using the ForeseeHome device for 2 years when a change in test
      scores prompted an examination (an alert visit) to search for choroidal
      neovascularization (CNV) in his right eye. He denied any vision changes, and
      visual acuity remained 20/20 in the right eye. Fundus examination showed large
      drusen without any signs of CNV. The late phase of a fluorescein angiogram showed
      a small juxtafoveal area of subretinal leakage which corresponded to an
      intraretinal cystoid abnormality on optical coherence tomography. Intravitreal
      ranibizumab therapy was initiated, and the patient has maintained excellent
      visual acuity for at least 1 year. Case 2, a 67-year-old woman, had been using
      the home device for 3 months when an alert notification was prompted in the left
      eye. On notification, she recognized that she had had a subtle change in her
      vision in that eye with new distortion. Visual acuity decreased to 20/32 in the
      left eye. Fundus examination revealed stable confluent drusen without any
      apparent fluid, blood, or lipid. No definite fluorescein angiogram leakage was
      identified among the hyperfluorescent staining of extensive drusen. However,
      optical coherence tomography showed a cystoid abnormality in the inner plexiform
      layer prompting the initiation of intravitreal ranibizumab under the assumption
      that the changes represented CNV. CONCLUSION: The home monitoring device has been
      proven to facilitate early detection of CNV associated with age-related macular
      degeneration. These two cases highlight early diagnosis of CNV heralded by the
      device. Visual acuity remained 20/32 or better, minimal or no fluorescein
      angiogram leakage was found, and subtle cystoid abnormalities appeared on optical
      coherence tomography.

PMID- 25383858
TI  - Choroidal metastases 34 years after remission of breast cancer.
AB  - PURPOSE: To report a case of choroidal metastases from breast carcinoma occurring
      after a remission period of 34 years. METHODS: Case report and literature review.
      RESULTS: A 77-year-old woman who presented with blurry vision was found to have
      choroidal metastatic lesions in both her eyes. She had a remote history of breast
      cancer (status post mastectomy) 34 years ago. A metastatic workup was performed
      that revealed the presence of widespread metastatic lesions in the lungs, liver,
      and bones. CONCLUSION: Although the median time period for the detection of
      choroidal metastases is 3 years after the diagnosis of the primary malignancy,
      choroidal metastases can present till 34 years later as in our case (the longest
      time interval reported in the literature).

PMID- 25383860
TI  - An otherwise healthy young man presents with bilateral CRVO as the first sign of
      hyperviscosity syndrome in the setting of new multiple myeloma.
AB  - PURPOSE: To report a case of bilateral central retinal vein occlusion as the
      presenting feature of new onset multiple myeloma in an otherwise healthy man.
      METHODS: A 44-year-old man presented with painless visual changes in his left
      eye. Ophthalmic examination revealed what appeared to be bilateral central
      retinal vein occlusion and hematologic assessment resulted in the diagnosis of
      immunoglobulin G multiple myeloma. RESULTS: Initial management was plasma
      exchange followed by a chemotherapy regimen of cyclophosphamide, bortezomib, and
      dexamethasone, and subsequent plans for bone marrow transplant. CONCLUSION:
      Hyperviscosity syndrome seems similar to central retinal vein occlusion and may
      be associated with systemic conditions such as diabetes and atherosclerosis;
      however, alternative etiologies should be considered in young otherwise healthy
      individuals. This case underscores the need for diligent and thorough
      investigations for less common systemic conditions associated with retinal vein
      occlusions by primary care ophthalmologists.

PMID- 25383859
TI  - New insights into acute annular outer retinopathy.
AB  - PURPOSE: Acute annular outer retinopathy is a rare entity. There are only a few
      cases in the world's literature. Our study is the first to describe the spectral
      domain optical coherence tomography (OCT) findings in the acute presentation of
      this disease and to follow the disease in convalescence. METHODS: This article is
      a descriptive case report. We used Spectralis OCT to image the transient
      intraretinal whitening that is initially seen in this disorder, and the OCT
      changes during follow-up. RESULTS: Our article provides additional information
      about the natural history of this uncommon disease, and its varied presentation
      and prognosis. We were able to document the initial white line seen in the acute
      phase of the disease and correlate it anatomically by using OCT. We found
      hyperreflectivity in the outer nuclear layer and the Henle fiber layer along with
      marked atrophy of the outer retina within the white ring. We documented
      restoration of foveal photoreceptors, which corresponded with visual recovery. We
      also noted progressive atrophy in areas where the white ring was previously
      visible. CONCLUSION: We describe a single case of acute annular outer retinopathy
      with the corresponding spectral domain OCT findings during the acute phase of the
      disease and during subsequent follow-up demonstrating progressive atrophy of the
      outer retina. This may shed insight into possible causation for this rare
      disease.

PMID- 25383861
TI  - Third time spontaneous closure of myopic macular hole.
AB  - PURPOSE: To describe the spontaneous closure of a myopic macular hole occurring
      three times. METHODS: A 75-year-old high myopic woman presented with decreased
      visual acuity and a deep small full-thickness macular hole in the left eye. The
      hole spontaneously resolved within 2 months. One year later, the patient returned
      with decreased visual acuity and severe metamorphopsia. A full-thickness macular
      hole was observed again. The hole spontaneously resolved 1 month later. Six
      months later, the patient presented again with decreased visual acuity and
      macular hole, the hole spontaneously resolved within 2 months. Optical coherence
      tomography was obtained during all visits. RESULTS: Initial optical coherence
      tomography revealed a small macular hole with bridging elements. At subsequent
      visits, optical coherence tomography showed resolution and recurrence of the hole
      twice. CONCLUSION: Dynamic interaction between tensile and degenerative forces,
      and proliferative and reparative glial elements, may lead to hole remodeling.

PMID- 25383862
TI  - Best disease associated with macular hole.
AB  - PURPOSE: To report a case of Best vitelliform macular dystrophy complicated by
      macular hole. METHODS: History and clinical examination, electroretinogram, and
      optical coherence tomography. RESULTS: We report a case of a 20-year-old boy with
      progressive visual loss in his left eye. In fundus examination, there was a
      typical vitelliform lesion in the right eye and a macular hole in the left eye.
      The electroretinogram Arden ratio was <1.1 in both eyes. Optical coherence
      tomography revealed deposition of hyperreflective material and hyporeflective
      area between the junction of the inner segment and outer segment of the
      photoreceptors and the retinal pigment epithelium in the right eye, and large
      full-thickness macular hole with cystoid changes in the retinal layers in the
      left eye. There was no associated retinal detachment. CONCLUSION: Although
      extremely rare, macular hole should be considered as a cause of the significant
      visual loss in patients with Best vitelliform macular dystrophy.

PMID- 25383863
TI  - Thickened retinal ganglion cell complex in patient with severe Takayasu
      retinopathy at early stage.
AB  - PURPOSE: Takayasu arteritis is caused by an autoimmune process that results in
      chronic granulomatous inflammation. We describe the optical coherence tomographic
      findings in a case of Stage 4 Takayasu retinopathy. METHODS: Case report and
      evaluation by optical coherence tomography. PATIENT: A 31-year-old woman visited
      our clinic because of bilateral blurred vision that began 1 month earlier.
      Examination showed that her visual acuities were 20/33 in the right and 20/100 in
      the left. The anterior segments were normal but retinal arteriovenous anastomosis
      shunts were detected on the optic disk of the both eyes, and vitreous hemorrhage
      was found in the left eye. RESULTS: Spectral domain optical coherence tomography
      showed a thickening of the retinal ganglion cell complex and inner plexiform
      layer around the optic disk with dilated retinal arteriovenous shunts near the
      nerve fiber layer. Irregular hyperreflectivity was also seen between the outer
      plexiform layer and the outer nuclear layer especially at the temporal raphe.
      Steroid pulse therapy was begun with 500 mg/day intravenous methylprednisolone
      for 3 days, followed by oral prednisolone and antiplatelet agents. After 2
      months, the retinal arteriovenous shunts on the optic disk of the right eye had a
      fibrovascular membrane-like appearance, and fluorescein angiography showed a
      progression of the retinal anastomosis and capillary nonperfusion especially in
      the temporal area. The thickened retinal ganglion cell complex around the optic
      disk remained but the irregular hyperreflectivity between the outer plexiform
      layer and the outer nuclear layer at the temporal raphe became smoother in both
      eyes. CONCLUSION: Optical coherence tomography can be useful in detecting retinal
      ischemia and the degree of inflammation in Takayasu retinopathy especially at the
      early stage.

PMID- 25383864
TI  - Links between N deposition and nitrate export from a high-elevation watershed in
      the Colorado Front Range.
AB  - Long-term patterns of stream nitrate export and atmospheric N deposition were
      evaluated over three decades in Loch Vale, a high-elevation watershed in the
      Colorado Front Range. Stream nitrate concentrations increased in the early 1990
      s, peaked in the mid-2000s, and have since declined by over 40%, coincident with
      trends in nitrogen oxide emissions over the past decade. Similarities in the
      timing and magnitude of N deposition provide evidence that stream chemistry is
      responding to changes in atmospheric deposition. The response to deposition was
      complicated by a drought in the early 2000s that enhanced N export for several
      years. Other possible explanations, including forest disturbance, snow depth, or
      permafrost melting, could not explain patterns in N export. Our results show that
      stream chemistry responds rapidly to changes in N deposition in high-elevation
      watersheds, similar to the response observed to changes in sulfur deposition.

PMID- 25383865
TI  - A longitudinal study of Steller sea lion natality rates in the Gulf of Alaska
      with comparisons to census data.
AB  - Steller sea lion (Eumetopias jubatus) numbers in the Western Distinct Population
      Segment are beginning to recover following the dramatic decline that began in the
      1970s and ended around the turn of the century. Low female reproductive rates
      (natality) may have contributed to the decline and remain an issue of concern for
      this population. During the 2000s we found high natality among Steller sea lions
      in the Gulf of Alaska indicating a healthy population. This study extends these
      previous estimates over an additional three years and tests for interannual
      variations and long-term trends. We further examine the proportions of pups to
      adult females observed on the rookery and nearby haulouts during the birthing
      season to assess whether census data can be used to estimate natality. Open
      robust design multistate models were built and tested using Program MARK to
      estimate survival, resighting, and state transition probabilities in addition to
      other parameters dependent on whether or not a female gave birth in the previous
      year. Natality was estimated at 70% with some evidence of interannual variation
      but a long-term increasing or decreasing trend was not supported by the data.
      Bootstrap and regression comparisons of census data with natality estimates
      revealed no correlation between the two methods suggesting that census data are
      not an appropriate proxy for natality in this species. Longitudinal studies of
      individual animals are an appropriate method for estimating vital rates in
      species with variable detection over time such as the Steller sea lion. This work
      indicates that natality remains high in this region and is consistent with a
      population in recovery. 

PMID- 25383867
TI  - Spontaneous ovarian hyperstimulation mimicking ovarian neoplasm: A rare
      complication of hypothyroidism.

PMID- 25383866
TI  - Results of a "GWAS plus:" general cognitive ability is substantially heritable
      and massively polygenic.
AB  - We carried out a genome-wide association study (GWAS) for general cognitive
      ability (GCA) plus three other analyses of GWAS data that aggregate the effects
      of multiple single-nucleotide polymorphisms (SNPs) in various ways. Our
      multigenerational sample comprised 7,100 Caucasian participants, drawn from two
      longitudinal family studies, who had been assessed with an age-appropriate IQ
      test and had provided DNA samples passing quality screens. We conducted the GWAS
      across ~ 2.5 million SNPs (both typed and imputed), using a generalized least
      squares method appropriate for the different family structures present in our
      sample, and subsequently conducted gene-based association tests. We also
      conducted polygenic prediction analyses under five-fold cross-validation, using
      two different schemes of weighting SNPs. Using parametric bootstrapping, we
      assessed the performance of this prediction procedure under the null. Finally, we
      estimated the proportion of variance attributable to all genotyped SNPs as random
      effects with software GCTA. The study is limited chiefly by its power to detect
      realistic single-SNP or single-gene effects, none of which reached genome-wide
      significance, though some genomic inflation was evident from the GWAS. Unit SNP
      weights performed about as well as least-squares regression weights under cross
      validation, but the performance of both increased as more SNPs were included in
      calculating the polygenic score. Estimates from GCTA were 35% of phenotypic
      variance at the recommended biological-relatedness ceiling. Taken together, our
      results concur with other recent studies: they support a substantial heritability
      of GCA, arising from a very large number of causal SNPs, each of very small
      effect. We place our study in the context of the literature-both contemporary and
      historical-and provide accessible explication of our statistical methods.

PMID- 25383868
TI  - Understanding the relationship between cotton fiber properties and non-cellulosic
      cell wall polysaccharides.
AB  - A detailed knowledge of cell wall heterogeneity and complexity is crucial for
      understanding plant growth and development. One key challenge is to establish
      links between polysaccharide-rich cell walls and their phenotypic
      characteristics. It is of particular interest for some plant material, like
      cotton fibers, which are of both biological and industrial importance. To this
      end, we attempted to study cotton fiber characteristics together with glycan
      arrays using regression based approaches. Taking advantage of the comprehensive
      microarray polymer profiling technique (CoMPP), 32 cotton lines from different
      cotton species were studied. The glycan array was generated by sequential
      extraction of cell wall polysaccharides from mature cotton fibers and screening
      samples against eleven extensively characterized cell wall probes. Also,
      phenotypic characteristics of cotton fibers such as length, strength, elongation
      and micronaire were measured. The relationship between the two datasets was
      established in an integrative manner using linear regression methods. In the
      conducted analysis, we demonstrated the usefulness of regression based approaches
      in establishing a relationship between glycan measurements and phenotypic traits.
      In addition, the analysis also identified specific polysaccharides which may play
      a major role during fiber development for the final fiber characteristics. Three
      different regression methods identified a negative correlation between micronaire
      and the xyloglucan and homogalacturonan probes. Moreover, homogalacturonan and
      callose were shown to be significant predictors for fiber length. The role of
      these polysaccharides was already pointed out in previous cell wall elongation
      studies. Additional relationships were predicted for fiber strength and
      elongation which will need further experimental validation. 

PMID- 25383869
TI  - Irritable bowel syndrome is positively related to metabolic syndrome: a
      population-based cross-sectional study.
AB  - Irritable bowel syndrome is a common gastrointestinal disorder that may affect
      dietary pattern, food digestion, and nutrient absorption. The nutrition-related
      factors are closely related to metabolic syndrome, implying that irritable bowel
      syndrome may be a potential risk factor for metabolic syndrome. However, few
      epidemiological studies are available which are related to this potential link.
      The purpose of this study is to determine whether irritable bowel syndrome is
      related to metabolic syndrome among middle-aged people. We designed a cross
      sectional study of 1,096 subjects to evaluate the relationship between irritable
      bowel syndrome and metabolic syndrome and its components. Diagnosis of irritable
      bowel syndrome was based on the Japanese version of the Rome III Questionnaire.
      Metabolic syndrome was defined according to the criteria of the American Heart
      Association scientific statements of 2009. Dietary consumption was assessed via a
      validated food frequency questionnaire. Principal-components analysis was used to
      derive 3 major dietary patterns: "Japanese", "sweets-fruits", and "Izakaya
      (Japanese Pub) "from 39 food groups. The prevalence of irritable bowel syndrome
      and metabolic syndrome were 19.4% and 14.6%, respectively. No significant
      relationship was found between the dietary pattern factor score tertiles and
      irritable bowel syndrome. After adjustment for potential confounders (including
      dietary pattern), the odds ratio (95% confidence interval) of having metabolic
      syndrome and elevated triglycerides for subjects with irritable bowel syndrome as
      compared with non-irritable bowel syndrome are 2.01(1.13-3.55) and 1.50(1.03
      2.18), respectively. Irritable bowel syndrome is significantly related to
      metabolic syndrome and it components. This study is the first to show that
      irritable bowel syndrome was significantly related to a higher prevalence of
      metabolic syndrome and elevated triglycerides among an adult population. The
      findings suggest that the treatment of irritable bowel syndrome may be a
      potentially beneficial factor for the prevention of metabolic syndrome. Further
      study is needed to clarify this association. 

PMID- 25383871
TI  - An experimental study of hafting adhesives and the implications for compound tool
      technology.
AB  - Experimental studies of hafting adhesives and modifications to compound tool
      components can demonstrate the extent to which human ancestors understood and
      exploited material properties only formally defined by science within the last
      century. Discoveries of Stone Age hafting adhesives at archaeological sites in
      Europe, the Middle East, and Africa have spurred experiments that sought to
      replicate or create models of such adhesives. Most of these studies, however,
      have been actualistic in design, focusing on replicating ancient applications of
      adhesive technology. In contrast, this study tested several glues based on Acacia
      resin within a materials science framework to better understand the effect of
      each adhesive ingredient on compound tool durability. Using an overlap joint as a
      model for a compound tool, adhesives formulated with loading agents from a range
      of particle sizes and mineral compositions were tested for toughness on smooth
      and rough substrates. Our results indicated that overlap joint toughness is
      significantly increased by using a roughened joint surface. Contrary to some
      previous studies, there was no evidence that particle size diversity in a loading
      agent improved adhesive effectiveness. Generally, glues containing quartz or
      ochre loading agents in the silt and clay-sized particle class yielded the
      toughest overlap joints, with the effect of particle size found to be more
      significant for rough rather than smooth substrate joints. Additionally, no
      particular ochre mineral or mineral mixture was found to be a clearly superior
      loading agent. These two points taken together suggest that Paleolithic use of
      ochre-loaded adhesives and the criteria used to select ochres for this purpose
      may have been mediated by visual and symbolic considerations rather than purely
      functional concerns. 

PMID- 25383872
TI  - Increased bone marrow (BM) plasma level of soluble CD30 and correlations with BM
      plasma level of interferon (IFN)-gamma, CD4/CD8 T-cell ratio and disease severity
      in aplastic anemia.
AB  - Idiopathic aplastic anemia (AA) is an immune-mediated bone marrow failure
      syndrome. Immune abnormalities such as decreased lymphocyte counts, inverted
      CD4/CD8 T-cell ratio and increased IFN-gamma-producing T cells have been found in
      AA. CD30, a surface protein belonging to the tumor necrosis factor receptor
      family and releasing from cell surface as a soluble form (sCD30) after
      activation, marks a subset of activated T cells secreting IFN-gamma when exposed
      to allogeneic antigens. Our study found elevated BM plasma levels of sCD30 in
      patients with SAA, which were closely correlated with disease severity, including
      absolute lymphocyte count (ALC) and absolute netrophil count (ANC). We also noted
      that sCD30 levels were positively correlated with plasma IFN-gamma levels and
      CD4/CD8 T-cell ratio in patients with SAA. In order to explain these phenomena,
      we stimulated T cells with alloantigen in vitro and found that CD30+ T cells were
      the major source of IFN-gamma, and induced CD30+ T cells from patients with SAA
      produced significantly more IFN-gamma than that from healthy individuals. In
      addition, increased proportion of CD8+ T cells in AA showed enhanced allogeneic
      response by the fact that they expressed more CD30 during allogeneic stimulation.
      sCD30 levels decreased in patients responded to immunosuppressive therapy. In
      conclusion, elevated BM plasma levels of sCD30 reflected the enhanced CD30+ T
      cell-mediated immune response in SAA. CD30 as a molecular marker that transiently
      expresses on IFN-gamma-producing T cells, may participate in mediating bone
      marrow failure in AA, which also can facilitate our understanding of AA
      pathogenesis to identify new therapeutic targets. 

PMID- 25383873
TI  - Filament-producing mutants of influenza A/Puerto Rico/8/1934 (H1N1) virus have
      higher neuraminidase activities than the spherical wild-type.
AB  - Influenza virus exhibits two morphologies - spherical and filamentous. Strains
      that have been grown extensively in laboratory substrates are comprised
      predominantly of spherical virions while clinical or low passage isolates produce
      a mixture of spheres and filamentous virions of varying lengths. The filamentous
      morphology can be lost upon continued passage in embryonated chicken eggs, a
      common laboratory substrate for influenza viruses. The fact that the filamentous
      morphology is maintained in nature but lost in favor of a spherical morphology in
      ovo suggests that filaments confer a selective advantage within the infected host
      that is not necessary for growth in laboratory substrates. Indeed, we have
      recently shown that filament-producing variant viruses are selected upon passage
      of the spherical laboratory strain A/Puerto Rico/8/1934 (H1N1) [PR8] in guinea
      pigs. Toward determining the nature of the selective advantage conferred by
      filaments, we sought to identify functional differences between spherical and
      filamentous particles. We compared the wild-type PR8 virus to two previously
      characterized recombinant PR8 viruses in which single point mutations within M1
      confer a filamentous morphology. Our results indicate that these filamentous PR8
      mutants have higher neuraminidase activities than the spherical PR8 virus.
      Conversely, no differences were observed in HAU:PFU or HAU:RNA ratios, binding
      avidity, sensitivity to immune serum in hemagglutination inhibition assays, or
      virion stability at elevated temperatures. Based on these results, we propose
      that the pleomorphic nature of influenza virus particles is important for the
      optimization of neuraminidase functions in vivo. 

PMID- 25383874
TI  - Separating macroecological pattern and process: comparing ecological, economic,
      and geological systems.
AB  - Theories of biodiversity rest on several macroecological patterns describing the
      relationship between species abundance and diversity. A central problem is that
      all theories make similar predictions for these patterns despite disparate
      assumptions. A troubling implication is that these patterns may not reflect
      anything unique about organizational principles of biology or the functioning of
      ecological systems. To test this, we analyze five datasets from ecological,
      economic, and geological systems that describe the distribution of objects across
      categories in the United States. At the level of functional form ('first-order
      effects'), these patterns are not unique to ecological systems, indicating they
      may reveal little about biological process. However, we show that mechanism can
      be better revealed in the scale-dependency of first-order patterns ('second-order
      effects'). These results provide a roadmap for biodiversity theory to move beyond
      traditional patterns, and also suggest ways in which macroecological theory can
      constrain the dynamics of economic systems. 

PMID- 25383877
TI  - Oxidative IR spectroelectrochemistry of copper in methanol containing carbon
      monoxide.
AB  - IR spectroelectrochemistry was used to examine the electro-oxidation behavior of
      carbon monoxide in methanol at a polycrystalline copper electrode. Under such
      neutral conditions copper electrodes are coated with ill-defined copper oxides
      and hydroxides and at the oxidative potentials can be expected to generate
      soluble copper species. The electrochemistry displayed complex behavior
      suggesting that methanol oxidation was one prominent reaction. However, the
      spectroscopy revealed that very little methanol oxidation had occurred and that
      carbon monoxide was not adsorbed to the copper electrode. Instead, the electro
      oxidation generated an intense IR band at 2107 cm(-1) that was attributed to a
      soluble [Cu(I)CO](+) species. 

PMID- 25383875
TI  - Limited density of an antigen presented by RMA-S cells requires B7-1/CD28
      signaling to enhance T-cell immunity at the effector phase.
AB  - The association of B7-1/CD28 between antigen presenting cells (APCs) and T-cells
      provides a second signal to proliferate and activate T-cell immunity at the
      induction phase. Many reports indicate that tumor cells transfected with B7-1
      induced augmented antitumor immunity at the induction phase by mimicking APC
      function; however, the function of B7-1 on antitumor immunity at the effector
      phase is unknown. Here, we report direct evidence of enhanced T-cell antitumor
      immunity at the effector phase by the B7-1 molecule. Our experiments in vivo and
      in vitro indicated that reactivity of antigen-specific monoclonal and polyclonal
      T-cell effectors against a Lass5 epitope presented by RMA-S cells is increased
      when the cells expressed B7-1. Use of either anti-B7-1 or anti-CD28 antibodies to
      block the B7-1/CD28 association reduced reactivity of the T effectors against B7
      1 positive RMA-S cells. Transfection of Lass5 cDNA into or pulse of Lass5 peptide
      onto B7-1 positive RMA-S cells overcomes the requirement of the B7-1/CD28 signal
      for T effector response. To our knowledge, the data offers, for the first time,
      strong evidence that supports the requirement of B7-1/CD28 secondary signal at
      the effector phase of antitumor T-cell immunity being dependent on the density of
      an antigenic peptide. 

PMID- 25383876
TI  - The E6AP binding pocket of the HPV16 E6 oncoprotein provides a docking site for a
      small inhibitory peptide unrelated to E6AP, indicating druggability of E6.
AB  - The HPV E6 oncoprotein maintains the malignant phenotype of HPV-positive cancer
      cells and represents an attractive therapeutic target. E6 forms a complex with
      the cellular E6AP ubiquitin ligase, ultimately leading to p53 degradation. The
      recently elucidated x-ray structure of a HPV16 E6/E6AP complex showed that HPV16
      E6 forms a distinct binding pocket for E6AP. This discovery raises the question
      whether the E6AP binding pocket is druggable, i. e. whether it provides a docking
      site for functional E6 inhibitors. To address these issues, we performed a
      detailed analysis of the HPV16 E6 interactions with two small peptides: (i)
      E6APpep, corresponding to the E6 binding domain of E6AP, and (ii) pep11**, a
      peptide that binds to HPV16 E6 and, in contrast to E6APpep, induces apoptosis,
      specifically in HPV16-positive cancer cells. Surface plasmon resonance, NMR
      chemical shift perturbation, and mammalian two-hybrid analyses coupled to
      mutagenesis indicate that E6APpep contacts HPV16 E6 amino acid residues within
      the E6AP pocket, both in vitro and intracellularly. Many of these amino acids
      were also important for binding to pep11**, suggesting that the binding sites for
      the two peptides on HPV16 E6 overlap. Yet, few E6 amino acids were differentially
      involved which may contribute to the higher binding affinity of pep11**. Data
      from the HPV16 E6/pep11** interaction allowed the rational design of single amino
      acid exchanges in HPV18 and HPV31 E6 that enabled their binding to pep11**. Taken
      together, these results suggest that E6 molecular surfaces mediating E6APpep
      binding can also accommodate pro-apoptotic peptides that belong to different
      sequence families. As proof of concept, this study provides the first
      experimental evidence that the E6AP binding pocket is druggable, opening new
      possibilities for rational, structure-based drug design. 

PMID- 25383878
TI  - Identification of a PRPF4 loss-of-function variant that abrogates U4/U6.U5 tri
      snRNP integration and is associated with retinitis pigmentosa.
AB  - Pre-mRNA splicing by the spliceosome is an essential step in the maturation of
      nearly all human mRNAs. Mutations in six spliceosomal proteins, PRPF3, PRPF4,
      PRPF6, PRPF8, PRPF31 and SNRNP200, cause retinitis pigmentosa (RP), a disease
      characterized by progressive photoreceptor degeneration. All splicing factors
      linked to RP are constituents of the U4/U6.U5 tri-snRNP subunit of the
      spliceosome, suggesting that the compromised function of this particle may lead
      to RP. Here, we report the identification of the p.R192H variant of the tri-snRNP
      factor PRPF4 in a patient with RP. The mutation affects a highly conserved
      arginine residue that is crucial for PRPF4 function. Introduction of a
      corresponding mutation into the zebrafish homolog of PRPF4 resulted in a complete
      loss of function in vivo. A series of biochemical experiments suggested that
      p.R192H disrupts the binding interface between PRPF4 and its interactor PRPF3.
      This interferes with the ability of PRPF4 to integrate into the tri-snRNP, as
      shown in a human cell line and in zebrafish embryos. These data suggest that the
      p.R192H variant of PRPF4 represents a functional null allele. The resulting
      haploinsufficiency of PRPF4 compromises the function of the tri-snRNP,
      reinforcing the notion that this spliceosomal particle is of crucial importance
      in the physiology of the retina. 

PMID- 25383880
TI  - Polyfluorene-sorted, carbon nanotube array field-effect transistors with
      increased current density and high on/off ratio.
AB  - Challenges in eliminating metallic from semiconducting single-walled carbon
      nanotubes (SWCNTs) and in controlling their alignment have limited the
      development of high-performance SWCNT-based field-effect transistors (FETs). We
      recently pioneered an approach for depositing aligned arrays of ultra-high-purity
      semiconducting SWCNTs, isolated using polyfluorene derivatives, called dose
      controlled floating evaporative self-assembly. Here, we tailor FETs fabricated
      from these arrays to achieve on-conductance (G(on)) per width and an on-off ratio
      (G(on)/G(off)) of 261 MUS/MUm and 2 * 10(5), respectively, for a channel length
      (L(ch)) of 240 nm and 116 MUS/MUm and 1 * 10(6), respectively, for an L(ch) of 1
      MUm. We demonstrate 1400* greater G(on)/G(off) than SWCNT FETs fabricated by
      other methods, at comparable G(on) per width of ~250 MUS/MUm and 30-100* greater
      G(on) per width at comparable G(on)/G(off) of 10(5)-10(7). The average G(on) per
      tube reaches 5.7 +/- 1.4 MUS at a packing density of 35 tubes/MUm for L(ch) in
      the range 160-240 nm, limited by contact resistance. These gains highlight the
      promise of using ultra-high-purity semiconducting SWCNTs with controlled
      alignment for next-generation semiconductor electronics.

PMID- 25383881
TI  - Inhibition of fumonisin B1 cytotoxicity by nanosilicate platelets during mouse
      embryo development.
AB  - Nanosilicate platelets (NSP), the form of natural silicate clay that was
      exfoliated from montmorillonite (MMT), is widely used as a feed additive for its
      high non-specific binding capacity with mycotoxins such as fumonisin B1 (FB1),
      and has been evaluated its safety for biomedical use including cytotoxicity,
      genotoxicity, and lethal dosage (LD). In the study, we further examined its
      toxicity on the development of CD1 mouse embryos and its capacity to prevent
      teratogenesis-induced by FB1. In vitro cultures, NSP did not disturb the
      development and the quality of intact pre-implantation mouse embryos. Further,
      newborn mice from females consumed with NSP showed no abnormalities. NSP had an
      unexpected high adsorption capacity in vitro. In contrast to female mice consumed
      with FB1 only, a very low residual level of FB1 in the circulation, reduced
      incidence of neutral tube defects and significantly increased fetal weight were
      observed in the females consumed with FB1 and NSP, suggesting a high alleviation
      effect of NSP on FB1 in vivo. Furthermore, FB1 treatment disturbed the gene
      expression of sphingolipid metabolism enzymes (longevity assurance homolog 5,
      LASS 5; sphingosine kinase 1, Sphk1; sphingosine kinase 2, Sphk2; sphingosine 1-
      phosphate lyase, Sgpl1; sphingosine 1-phosphate phosphatase, Sgpp1) in the
      maternal liver, uterus, fetus, and placenta, but NSP administration reversed the
      perturbations. Based on these findings, we conclude that NSP is a feasible and
      effective agent for supplementary use in reducing the toxicity of FB1 to animals.

PMID- 25383883
TI  - Analysis of feature intervisibility and cumulative visibility using GIS, Bayesian
      and spatial statistics: a study from the Mandara Mountains, northern Cameroon.
AB  - The locations of diy-gedelta-bay (DGB) sites in the Mandara Mountains, northern
      Cameroon are hypothesized to occur as a function of their ability to see and be
      seen from points on the surrounding landscape. A series of geostatistical, two
      way and Bayesian logistic regression analyses were performed to test two
      hypotheses related to the intervisibility of the sites to one another and their
      visual prominence on the landscape. We determine that the intervisibility of the
      sites to one another is highly statistically significant when compared to 10
      stratified-random permutations of DGB sites. Bayesian logistic regression
      additionally demonstrates that the visibility of the sites to points on the
      surrounding landscape is statistically significant. The location of sites appears
      to have also been selected on the basis of lower slope than random permutations
      of sites. Using statistical measures, many of which are not commonly employed in
      archaeological research, to evaluate aspects of visibility on the landscape, we
      conclude that the placement of DGB sites improved their conspicuousness for
      enhanced ritual, social cooperation and/or competition purposes.

PMID- 25383882
TI  - Positive end-expiratory pressure and variable ventilation in lung-healthy rats
      under general anesthesia.
AB  - OBJECTIVES: Variable ventilation (VV) seems to improve respiratory function in
      acute lung injury and may be combined with positive end-expiratory pressure
      (PEEP) in order to protect the lungs even in healthy subjects. We hypothesized
      that VV in combination with moderate levels of PEEP reduce the deterioration of
      pulmonary function related to general anesthesia. Hence, we aimed at evaluating
      the alveolar stability and lung protection of the combination of VV at different
      PEEP levels. DESIGN: Randomized experimental study. SETTING: Animal research
      facility. SUBJECTS: Forty-nine male Wistar rats (200-270 g). INTERVENTIONS:
      Animals were ventilated during 2 hours with protective low tidal volume (VT) in
      volume control ventilation (VCV) or VV and PEEP adjusted at the level of minimum
      respiratory system elastance (Ers), obtained during a decremental PEEP trial
      subsequent to a recruitment maneuver, and 2 cmH2O above or below of this level.
      MEASUREMENTS AND MAIN RESULTS: Ers, gas exchange and hemodynamic variables were
      measured. Cytokines were determined in lung homogenate and plasma samples and
      left lung was used for histologic analysis and diffuse alveolar damage scoring. A
      progressive time-dependent increase in Ers was observed independent on
      ventilatory mode or PEEP level. Despite of that, the rate of increase of Ers and
      lung tissue IL-1 beta concentration were significantly lower in VV than in VCV at
      the level of the PEEP of minimum Ers. A significant increase in lung tissue
      cytokines (IL-6, IL-1 beta, CINC-1 and TNF-alpha) as well as a ventral to dorsal
      and cranial to caudal reduction in aeration was observed in all ventilated rats
      with no significant differences among groups. CONCLUSIONS: VV combined with PEEP
      adjusted at the level of the PEEP of minimal Ers seemed to better prevent
      anesthesia-induced atelectasis and might improve lung protection throughout
      general anesthesia.

PMID- 25383879
TI  - Nerve growth factor regulates neurolymphatic remodeling during corneal
      inflammation and resolution.
AB  - The cellular and physiologic mechanisms that regulate the resolution of
      inflammation remain poorly defined despite their widespread importance in
      improving inflammatory disease outcomes. We studied the resolution of two
      cardinal signs of inflammation-pain and swelling-by investigating molecular
      mechanisms that regulate neural and lymphatic vessel remodeling during the
      resolution of corneal inflammation. A mouse model of corneal inflammation and
      wound recovery was developed to study this process in vivo. Administration of
      nerve growth factor (NGF) increased pain sensation and inhibited neural
      remodeling and lymphatic vessel regression processes during wound recovery. A
      complementary in vivo approach, the corneal micropocket assay, revealed that NGF
      laden pellets stimulated lymphangiogenesis and increased protein levels of VEGF
      C. Adult human dermal lymphatic endothelial cells did not express canonical NGF
      receptors TrkA and p75NTR or activate downstream MAPK- or Akt-pathway effectors
      in the presence of NGF, although NGF treatment increased their migratory and
      tubulogenesis capacities in vitro. Blockade of the VEGF-R2/R3 signaling pathway
      ablated NGF-mediated lymphangiogenesis in vivo. These findings suggest a
      hierarchical relationship with NGF functioning upstream of the VEGF family
      members, particularly VEGF-C, to stimulate lymphangiogenesis. Taken together,
      these studies show that NGF stimulates lymphangiogenesis and that NGF may act as
      a pathogenic factor that negatively regulates the normal neural and lymphatic
      vascular remodeling events that accompany wound recovery. 

PMID- 25383884
TI  - Identification of different types of spinal afferent nerve endings that encode
      noxious and innocuous stimuli in the large intestine using a novel anterograde
      tracing technique.
AB  - In mammals, sensory stimuli in visceral organs, including those that underlie
      pain perception, are detected by spinal afferent neurons, whose cell bodies lie
      in dorsal root ganglia (DRG). One of the major challenges in visceral organs has
      been how to identify the different types of nerve endings of spinal afferents
      that transduce sensory stimuli into action potentials. The reason why spinal
      afferent nerve endings have been so challenging to identify is because no
      techniques have been available, until now, that can selectively label only spinal
      afferents, in high resolution. We have utilized an anterograde tracing technique,
      recently developed in our laboratory, which facilitates selective labeling of
      only spinal afferent axons and their nerve endings in visceral organs. Mice were
      anesthetized, lumbosacral DRGs surgically exposed, then injected with dextran
      amine. Seven days post-surgery, the large intestine was removed. The
      characteristics of thirteen types of spinal afferent nerve endings were
      identified in detail. The greatest proportion of nerve endings was in submucosa
      (32%), circular muscle (25%) and myenteric ganglia (22%). Two morphologically
      distinct classes innervated myenteric ganglia. These were most commonly a novel
      class of intraganglionic varicose endings (IGVEs) and occasionally rectal
      intraganglionic laminar endings (rIGLEs). Three distinct classes of varicose
      nerve endings were found to innervate the submucosa and circular muscle, while
      one class innervated internodal strands, blood vessels, crypts of lieberkuhn, the
      mucosa and the longitudinal muscle. Distinct populations of sensory endings were
      CGRP-positive. We present the first complete characterization of the different
      types of spinal afferent nerve endings in a mammalian visceral organ. The
      findings reveal an unexpectedly complex array of different types of primary
      afferent endings that innervate specific layers of the large intestine. Some of
      the novel classes of nerve endings identified must underlie the transduction of
      noxious and/or innocuous stimuli from the large intestine. 

PMID- 25383887
TI  - Functional potential of soil microbial communities in the maize rhizosphere.
AB  - Microbial communities in the rhizosphere make significant contributions to crop
      health and nutrient cycling. However, their ability to perform important
      biogeochemical processes remains uncharacterized. Here, we identified important
      functional genes that characterize the rhizosphere microbial community to
      understand metabolic capabilities in the maize rhizosphere using the GeoChip
      based functional gene array method. Significant differences in functional gene
      structure were apparent between rhizosphere and bulk soil microbial communities.
      Approximately half of the detected gene families were significantly (p<0.05)
      increased in the rhizosphere. Based on the detected gyrB genes,
      Gammaproteobacteria, Betaproteobacteria, Firmicutes, Bacteroidetes and
      Cyanobacteria were most enriched in the rhizosphere compared to those in the bulk
      soil. The rhizosphere niche also supported greater functional diversity in
      catabolic pathways. The maize rhizosphere had significantly enriched genes
      involved in carbon fixation and degradation (especially for hemicelluloses,
      aromatics and lignin), nitrogen fixation, ammonification, denitrification,
      polyphosphate biosynthesis and degradation, sulfur reduction and oxidation. This
      research demonstrates that the maize rhizosphere is a hotspot of genes, mostly
      originating from dominant soil microbial groups such as Proteobacteria, providing
      functional capacity for the transformation of labile and recalcitrant organic C,
      N, P and S compounds.

PMID- 25383889
TI  - Chemical bonding in a linear chromium metal string complex.
AB  - A combined experimental and theoretical electron density study of the shortest
      trichromium metal wire, Cr3(dpa)4Cl2.(C2H5OC2H5)(x)(CH2Cl2)(1-x) (1, dpa = bis(2
      pyridyl)amido), is reported. High resolution X-ray diffraction data has been
      collected both at 100 K using a conventional X-ray source (DS1) and at 15 K using
      a synchrotron X-ray source (DS2). The linear chromium string is terminated by Cl(
      ) ions at both ends, and each Cr atom is also coordinated by four N atoms from
      bridging dpa ligands. The two Cr-Cr bond distances are unequal at 100 K (with
      d(Cr1-Cr2) being 0.029 A shorter than d(Cr2-Cr3)) but at 15 K they are almost
      equal (0.002 A difference). Analysis of the slightly elongated thermal ellipsoids
      of the Cr2 atom suggests that it is not due to disorder, but the presence of a
      shallow potential energy surface. Laplacian maps clearly show local valence shell
      charge concentration (VSCC) in the electron density along the bisector of the
      equatorial Cr-N bonds. Integration over the atomic basins indicates that Cr2 has
      smaller atomic charge and volume than Cr1 and Cr3. The topological
      characterization of the Cr-Cr bonds indicates partly covalent characters with
      electron density at the bond critical point of ~0.3 e A(-3) and negative total
      energy density. The delocalization index of Cr-Cr is 0.8 for Cr1-Cr2 and 0.08 for
      Cr1-Cr3. Second-order perturbation analysis shows high stabilization energy of
      the Cr-Cr bonds (E(2) ~ 190 kcal mol(-1)). Delocalization indices and source
      function and natural bond orbital analyses are all indicative of localized Cr-Cr
      bonding interactions.

PMID- 25383888
TI  - Resequencing microarray technology for genotyping human papillomavirus in
      cervical smears.
AB  - There are more than 40 human papillomaviruses (HPVs) belonging to the alpha genus
      that cause sexually transmitted infections; these infections are among the most
      frequent and can lead to condylomas and anogenital intra-epithelial neoplasia. At
      least 18 of these viruses are causative agents of anogenital carcinomas. We
      evaluated the performance of a resequencing microarray for the detection and
      genotyping of alpha HPV of clinical significance using cloned HPV DNA. To reduce
      the number of HPV genotypes tiled on microarray, we used reconstructed ancestral
      sequences (RASs) as they are more closely related to the various genotypes than
      the current genotypes are among themselves. The performance of this approach was
      tested by genotyping with a set of 40 cervical smears already genotyped using the
      commercial PapilloCheck kit. The results of the two tests were concordant for 70%
      (28/40) of the samples and compatible for 30% (12/40). Our findings indicate that
      RASs were able to detect and identify one or several HPV in clinical samples.
      Associating RASs with homonym sequences improved the genotyping of HPV present in
      cases of multiple infection. In conclusion, we demonstrate the diagnostic
      potential of resequencing technology for genotyping of HPV, and illustrate its
      value both for epidemiological studies and for monitoring the distribution of HPV
      in the post-vaccination era. 

PMID- 25383890
TI  - Accumulation of polyunsaturated aldehydes in the gonads of the copepod Acartia
      tonsa revealed by tailored fluorescent probes.
AB  - Polyunsaturated aldehydes (PUAs) are released by several diatom species during
      predation. Besides other attributed activities, these oxylipins can interfere
      with the reproduction of copepods, important predators of diatoms. While
      intensive research has been carried out to document the effects of PUAs on
      copepod reproduction, little is known about the underlying mechanistic aspects of
      PUA action. Especially PUA uptake and accumulation in copepods has not been
      addressed to date. To investigate how PUAs are taken up and interfere with the
      reproduction in copepods we developed a fluorescent probe containing the
      alpha,beta,gamma,delta-unsaturated aldehyde structure element that is essential
      for the activity of PUAs as well as a set of control probes. We developed
      incubation and monitoring procedures for adult females of the calanoid copepod
      Acartia tonsa and show that the PUA derived fluorescent molecular probe
      selectively accumulates in the gonads of this copepod. In contrast, a saturated
      aldehyde derived probe of an inactive parent molecule was enriched in the lipid
      sac. This leads to a model for PUAs' teratogenic mode of action involving
      accumulation and covalent interaction with nucleophilic moieties in the copepod
      reproductive tissue. The teratogenic effect of PUAs can therefore be explained by
      a selective targeting of the molecules into the reproductive tissue of the
      herbivores, while more lipophilic but otherwise strongly related structures end
      up in lipid bodies. 

PMID- 25383891
TI  - Effect of grain size and microstructure on radiation stability of CeO2: an
      extensive study.
AB  - To investigate the variation in the radiation stability of ceria with
      microstructure under the electronic excitation regime, ceria samples sintered
      under different conditions were irradiated with high energy 100 MeV Ag ions. The
      ceria nanopowders were synthesized and sintered at 800  degrees C (S800), 1000 
      degrees C (S1000) and 1300  degrees C (S1300), respectively. The samples with
      widely varying grain size, densities and microstructure were obtained. The
      pristine and irradiated samples were studied by X-ray diffraction (XRD), Scanning
      electron microscopy (SEM), Raman spectroscopy and X-ray photoelectron
      spectroscopy (XPS). None of the samples amorphized up to the highest fluence of 1
      * 10(14) ions per cm(2) employed in this study. XRD and Raman studies showed that
      the sample with lowest grain size suffered maximum damage while the sample with
      largest grain size was most stable and showed little change in crystallinity.
      Raman spectroscopy indicated the enhanced formation of Ce(3+) and related defects
      in the sample with larger grain size after irradiation. The most intriguing
      result was the absence of Ce(3+)-related defects in the sample with lowest grain
      size which actually showed maximum damage upon irradiation. The XPS studies on
      S800 and S1300 provided concrete evidence for the presence of Ce(3+) and oxygen
      ion vacancies in S1300. The grain boundaries and grain size dependent stability
      have been discussed. 

PMID- 25383893
TI  - Substrate specificities of the granzyme tryptases A and K.
AB  - The physiological roles of the granzymes A and K have been debated, especially
      concerning their involvement in cytotoxic and inflammatory processes. By
      performing N-terminal COFRADIC assisted N-terminomics on the homologous human
      granzymes A and K, we here provide detailed data on their substrate repertoires,
      their specificities, and differences in efficiency by which they cleave their
      substrates, all of which may aid in elucidating their key substrates. In
      addition, the so far uncharacterized mouse granzyme K was profiled alongside its
      human orthologue. While the global primary specificity profiles of these
      granzymes appear quite similar as they revealed only subtle differences and
      pointed to substrate occupancies in the P1, P1', and P2' position as the main
      determinants for substrate recognition, differential analyses unveiled
      distinguishing substrate subsite features, some of which were confirmed by the
      more selective cleavage of specifically designed probes. 

PMID- 25383894
TI  - Hormone receptor and HER2 status: The only predictive factors of response to
      neoadjuvant chemotherapy in breast cancer.
AB  - We report our experience in neoadjuvant breast cancer chemotherapy in a single
      centre between 2000 and 2011. We looked for predictive factors for response to
      neoadjuvant chemotherapy in the present study. A total of 110 consecutive breast
      cancer patients were treated with neoadjuvant chemotherapy in our centre.
      Pathological response was achieved in 24 HR+/HER2- (38.7%), 25 HER2+ (67.6%) and
      five triple-negative (45.5%) (p = 0.02) patients. No statistically significant
      differences were found in pathological tumour response according to T stage. The
      multivariate analysis revealed tumour subtype was the only associated factor for
      pathological response, with HER2 + tumours the best responders, OR 3.9 (1.5-9.9):
      5-year DFS was 40% HER2+/no response; 78% HER2+/response; 65% HR+/HER2-/no
      response; 82% HR+/HER2-/response; 25% triple-negative/no response and 100% triple
      negative/response. HR and HER2 status were the only prognostic factors for
      pathological response. pCR was correlated with survival in all tumour subtypes. 

PMID- 25383892
TI  - Exome sequencing for the diagnosis of 46,XY disorders of sex development.
AB  - CONTEXT: Disorders of sex development (DSD) are clinical conditions where there
      is a discrepancy between the chromosomal sex and the phenotypic (gonadal or
      genital) sex of an individual. Such conditions can be stressful for patients and
      their families and have historically been difficult to diagnose, especially at
      the genetic level. In particular, for cases of 46,XY gonadal dysgenesis, once
      variants in SRY and NR5A1 have been ruled out, there are few other single gene
      tests available. OBJECTIVE: We used exome sequencing followed by analysis with a
      list of all known human DSD-associated genes to investigate the underlying
      genetic etiology of 46,XY DSD patients who had not previously received a genetic
      diagnosis. DESIGN: Samples were either submitted to the research laboratory or
      submitted as clinical samples to the UCLA Clinical Genomic Center. Sequencing
      data were filtered using a list of genes known to be involved in DSD. RESULTS: We
      were able to identify a likely genetic diagnosis in more than a third of cases,
      including 22.5% with a pathogenic finding, an additional 12.5% with likely
      pathogenic findings, and 15% with variants of unknown clinical significance.
      CONCLUSIONS: Early identification of the genetic cause of a DSD will in many
      cases streamline and direct the clinical management of the patient, with more
      focused endocrine and imaging studies and better-informed surgical decisions.
      Exome sequencing proved an efficient method toward such a goal in 46,XY DSD
      patients.

PMID- 25383895
TI  - Simultaneous reduction of arsenic(V) and uranium(VI) by mackinawite: role of
      uranyl arsenate precipitate formation.
AB  - Uranium (U) and arsenic (As) often occur together naturally and, as a result, can
      be co-contaminants at sites of uranium mining and processing, yet few studies
      have examined the simultaneous redox dynamics of U and As. This study examines
      the influence of arsenate (As(V)) on the reduction of uranyl (U(VI)) by the redox
      active mineral mackinawite (FeS). As(V) was added to systems containing 47 or 470
      MUM U(VI) at concentrations ranging from 0 to 640 MUM. In the absence of As(V), U
      was completely removed from solution and fully reduced to nano-uraninite (nano
      UO2). While the addition of As(V) did not reduce U uptake, at As(V)
      concentrations above 320 MUM, the reduction of U(VI) was limited due to the
      formation of a trogerite-like uranyl arsenate precipitate. The presence of U also
      significantly inhibited As(V) reduction. While less U(VI) reduction to nano-UO2
      may take place in systems with high As(V) concentrations, formation of trogerite
      like mineral phases may be an acceptable reclamation end point due to their high
      stability under oxic conditions. 

PMID- 25383896
TI  - Herringbone to cofacial solid state packing via H-bonding in diketopyrrolopyrrole
      (DPP) based molecular crystals: influence on charge transport.
AB  - The mono-alkylation of DPP derivatives leads to cofacial pi-pi stacking via H
      bonding unlike their di-alkylated counterparts, which exhibit a classical
      herringbone packing pattern. Single crystal organic field-effect transistor
      (OFET) measurements reveal a significant enhancement of charge carrier mobility
      for mono-hexyl DPP derivatives. 

PMID- 25383897
TI  - The instruments in the first psychological laboratory in Mexico: antecedents,
      influence, and methods.
AB  - Enrique O. Aragon established the first psychological laboratory in Mexico in
      1916. This laboratory was inspired by Wundt's laboratory and by those created
      afterward in Germany and the United States. It was equipped with state-of-the art
      instruments imported from Germany in 1902 from Ernst Zimmermann who supplied
      instruments for Wundt's laboratory. Although previous authors have described the
      social events leading to the creation of the laboratory, there are limited
      descriptions of the instruments, their use, and their influence. With the aid of
      archival resources, the initial location of the laboratory was determined. The
      analysis of instruments revealed a previously overlooked relation with a previous
      laboratory of experimental physiology. The influence of the laboratory was traced
      by describing the careers of 4 students, 3 of them women, who worked with the
      instruments during the first 2 decades of the 20th century, each becoming
      accomplished scholars. In addition, this article, by identifying and analyzing
      the instruments shown in photographs of the psychological laboratory and in 1
      motion film, provides information of the class demonstrations and the experiments
      conducted in this laboratory.

PMID- 25383899
TI  - Mechanism and treatment for learning and memory deficits in mouse models of
      Noonan syndrome.
AB  - In Noonan syndrome (NS) 30-50% of subjects show cognitive deficits of unknown
      etiology and with no known treatment. Here, we report that knock-in mice
      expressing either of two NS-associated mutations in Ptpn11, which encodes the
      nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent
      impairments in spatial learning and deficits in hippocampal long-term
      potentiation (LTP). In addition, viral overexpression of an NS-associated allele
      PTPN11(D61G) in adult mouse hippocampus results in increased baseline excitatory
      synaptic function and deficits in LTP and spatial learning, which can be reversed
      by a mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, brief
      treatment with lovastatin reduces activation of the GTPase Ras-extracellular
      signal-related kinase (Erk) pathway in the brain and normalizes deficits in LTP
      and learning in adult Ptpn11(D61G/+) mice. Our results demonstrate that increased
      basal Erk activity and corresponding baseline increases in excitatory synaptic
      function are responsible for the LTP impairments and, consequently, the learning
      deficits in mouse models of NS. These data also suggest that lovastatin or MEK
      inhibitors may be useful for treating the cognitive deficits in NS. 

PMID- 25383900
TI  - A hierarchy of intrinsic timescales across primate cortex.
AB  - Specialization and hierarchy are organizing principles for primate cortex, yet
      there is little direct evidence for how cortical areas are specialized in the
      temporal domain. We measured timescales of intrinsic fluctuations in spiking
      activity across areas and found a hierarchical ordering, with sensory and
      prefrontal areas exhibiting shorter and longer timescales, respectively. On the
      basis of our findings, we suggest that intrinsic timescales reflect areal
      specialization for task-relevant computations over multiple temporal ranges. 

PMID- 25383901
TI  - Molecular and functional definition of the developing human striatum.
AB  - The complexity of the human brain derives from the intricate interplay of
      molecular instructions during development. Here we systematically investigated
      gene expression changes in the prenatal human striatum and cerebral cortex during
      development from post-conception weeks 2 to 20. We identified tissue-specific
      gene coexpression networks, differentially expressed genes and a minimal set of
      bimodal genes, including those encoding transcription factors, that distinguished
      striatal from neocortical identities. Unexpected differences from mouse striatal
      development were discovered. We monitored 36 determinants at the protein level,
      revealing regional domains of expression and their refinement, during striatal
      development. We electrophysiologically profiled human striatal neurons
      differentiated in vitro and determined their refined molecular and functional
      properties. These results provide a resource and opportunity to gain global
      understanding of how transcriptional and functional processes converge to specify
      human striatal and neocortical neurons during development. 

PMID- 25383902
TI  - A category-free neural population supports evolving demands during decision
      making.
AB  - The posterior parietal cortex (PPC) receives diverse inputs and is involved in a
      dizzying array of behaviors. These many behaviors could rely on distinct
      categories of neurons specialized to represent particular variables or could rely
      on a single population of PPC neurons that is leveraged in different ways. To
      distinguish these possibilities, we evaluated rat PPC neurons recorded during
      multisensory decisions. Newly designed tests revealed that task parameters and
      temporal response features were distributed randomly across neurons, without
      evidence of categories. This suggests that PPC neurons constitute a dynamic
      network that is decoded according to the animal's present needs. To test for an
      additional signature of a dynamic network, we compared moments when behavioral
      demands differed: decision and movement. Our new state-space analysis revealed
      that the network explored different dimensions during decision and movement.
      These observations suggest that a single network of neurons can support the
      evolving behavioral demands of decision-making. 

PMID- 25383905
TI  - Supramolecular assemblies of novel aminonucleoside phospholipids and their
      bonding to nucleic acids.
AB  - A novel class of aminonucleoside phospholipids has been developed. These
      molecules could spontaneously assemble into supramolecular structures including
      multilamellar organization, hydrogels, superhelical strands, and vesicles. Their
      ability to bind to DNA by hydrogen bonding and pi-pi stacking interactions was
      investigated by many means. 

PMID- 25383906
TI  - The predictive performance and stability of six species distribution models.
AB  - BACKGROUND: Predicting species' potential geographical range by species
      distribution models (SDMs) is central to understand their ecological
      requirements. However, the effects of using different modeling techniques need
      further investigation. In order to improve the prediction effect, we need to
      assess the predictive performance and stability of different SDMs. METHODOLOGY:
      We collected the distribution data of five common tree species (Pinus massoniana,
      Betula platyphylla, Quercus wutaishanica, Quercus mongolica and Quercus
      variabilis) and simulated their potential distribution area using 13
      environmental variables and six widely used SDMs: BIOCLIM, DOMAIN, MAHAL, RF,
      MAXENT, and SVM. Each model run was repeated 100 times (trials). We compared the
      predictive performance by testing the consistency between observations and
      simulated distributions and assessed the stability by the standard deviation,
      coefficient of variation, and the 99% confidence interval of Kappa and AUC
      values. RESULTS: The mean values of AUC and Kappa from MAHAL, RF, MAXENT, and SVM
      trials were similar and significantly higher than those from BIOCLIM and DOMAIN
      trials (p<0.05), while the associated standard deviations and coefficients of
      variation were larger for BIOCLIM and DOMAIN trials (p<0.05), and the 99%
      confidence intervals for AUC and Kappa values were narrower for MAHAL, RF,
      MAXENT, and SVM. Compared to BIOCLIM and DOMAIN, other SDMs (MAHAL, RF, MAXENT,
      and SVM) had higher prediction accuracy, smaller confidence intervals, and were
      more stable and less affected by the random variable (randomly selected pseudo
      absence points). CONCLUSIONS: According to the prediction performance and
      stability of SDMs, we can divide these six SDMs into two categories: a high
      performance and stability group including MAHAL, RF, MAXENT, and SVM, and a low
      performance and stability group consisting of BIOCLIM, and DOMAIN. We highlight
      that choosing appropriate SDMs to address a specific problem is an important part
      of the modeling process.

PMID- 25383903
TI  - Dendritic channelopathies contribute to neocortical and sensory hyperexcitability
      in Fmr1(-/y) mice.
AB  - Hypersensitivity in response to sensory stimuli and neocortical hyperexcitability
      are prominent features of Fragile X Syndrome (FXS) and autism spectrum disorders,
      but little is known about the dendritic mechanisms underlying these phenomena. We
      found that the primary somatosensory neocortex (S1) was hyperexcited in response
      to tactile sensory stimulation in Fmr1(-/y) mice. This correlated with neuronal
      and dendritic hyperexcitability of S1 pyramidal neurons, which affect all major
      aspects of neuronal computation, from the integration of synaptic input to the
      generation of action potential output. Using dendritic electrophysiological
      recordings, calcium imaging, pharmacology, biochemistry and a computer model, we
      found that this defect was, at least in part, attributable to the reduction and
      dysfunction of dendritic h- and BKCa channels. We pharmacologically rescued
      several core hyperexcitability phenomena by targeting BKCa channels. Our results
      provide strong evidence pointing to the utility of BKCa channel openers for the
      treatment of the sensory hypersensitivity aspects of FXS. 

PMID- 25383907
TI  - Depassivation of aged Fe 0 by divalent cations: correlation between contaminant
      degradation and surface complexation constants.
AB  - The dechlorination of trichloroethylene (TCE) by aged Fe(0) in the presence of a
      series of divalent cations was investigated with the result that while no
      significant degradation of TCE was observed in Milli-Q water or in solutions of
      Ba(2+), Sr(2+), or Ca(2+), very effective TCE removal was observed in solutions
      containing Mg(2+), Mn(2+), Co(2+), Fe(2+), Ni(2+), Zn(2+), Cu(2+), or Pb(2+). The
      rate constants of TCE removal in the presence of particular cations were
      positively correlated to the log K representing the affinity of the cations for
      hydrous ferric oxide (HFO) surface sites though the treatments with Co(2+) and
      Ni(2+) were found to provide particularly strong enhancement in TCE degradation
      rate. The extent of Fe(II) release to solution also increased with increase in
      log K, while the solution pH from both experimental measurement and thermodynamic
      calculation decreased with increasing log K. While the peak areas of Fe and O XPS
      spectra of the passivated ZVI in the presence of Ba(2+), Sr(2+), and Ca(2+) were
      very close to those in Milli-Q water, very significant increases in surface Fe
      and O (and OH) were observed in solutions of Mg(2+), Mn(2+), Co(2+), Fe(2+),
      Ni(2+), Zn(2+), Cu(2+) and Pb(2+), revealing that the surface oxide layer
      dissolution is consistent with the recovery of aged Fe(0) with respect to TCE
      degradation. The depassivation process is proposed to involve (i) surface
      complexation of cations on surface coatings of aged Fe(0), (ii) dissolution of
      the hydrated surface as a consequence of magnetite exposure, and (iii) transport
      of electrons from underlying Fe(0) via magnetite to TCE, resulting in TCE
      dechlorination and, for some cations (Co(2+), Ni(2+), Cu(2+), and Pb(2+)),
      reduction to their zero or +1 valence state (with potential for these reduced
      metals to enhance TCE degradation). 

PMID- 25383908
TI  - Absorbed dose measurements for kV-cone beam computed tomography in image-guided
      radiation therapy.
AB  - In this study, we develope a novel method to directly evaluate an absorbed dose
      to-water for kilovoltage-cone beam computed tomography (kV-CBCT) in image-guided
      radiation therapy (IGRT). Absorbed doses for the kV-CBCT systems of the Varian On
      Board Imager (OBI) and the Elekta X-ray Volumetric Imager (XVI) were measured by
      a Farmer ionization chamber with a (60)Co calibration factor. The chamber
      measurements were performed at the center and four peripheral points in body-type
      (30 cm diameter and 51 cm length) and head-type (16 cm diameter and 33 cm length)
      cylindrical water phantoms. The measured ionization was converted to the absorbed
      dose-to-water by using a (60)Co calibration factor and a Monte Carlo (MC)
      calculated beam quality conversion factor, kQ, for (60)Co to kV-CBCT. The
      irradiation for OBI and XVI was performed with pelvis and head modes for the body
      and the head-type phantoms, respectively. In addition, the dose distributions in
      the phantom for both kV-CBCT systems were calculated with MC method and were
      compared with measured values. The MC-calculated doses were calibrated at the
      center in the water phantom and compared with measured doses at four peripheral
      points. The measured absorbed doses at the center in the body-type phantom were
      1.96 cGy for OBI and 0.83 cGy for XVI. The peripheral doses were 2.36-2.90 cGy
      for OBI and 0.83-1.06 cGy for XVI. The doses for XVI were lower up to
      approximately one-third of those for OBI. Similarly, the measured doses at the
      center in the head-type phantom were 0.48 cGy for OBI and 0.21 cGy for XVI. The
      peripheral doses were 0.26-0.66 cGy for OBI and 0.16-0.30 cGy for XVI. The
      calculated peripheral doses agreed within 3% in the pelvis mode and within 4% in
      the head mode with measured doses for both kV-CBCT systems. In addition, the
      absorbed dose determined in this study was approximately 4% lower than that in TG
      61 but the absorbed dose by both methods was in agreement within their combined
      uncertainty. This method is more robust and accurate compared to the dosimetry
      based on a conventional air-kerma calibration factor. Therefore, it is possible
      to be used as a standard dosimetry protocol for kV-CBCT in IGRT.

PMID- 25383904
TI  - Leptin-inhibited PBN neurons enhance responses to hypoglycemia in negative energy
      balance.
AB  - Hypoglycemia initiates the counter-regulatory response (CRR), in which the
      sympathetic nervous system, glucagon and glucocorticoids restore glucose to
      appropriate concentrations. During starvation, low leptin levels restrain energy
      utilization, enhancing long-term survival. To ensure short-term survival during
      hypoglycemia in fasted animals, the CRR must overcome this energy-sparing program
      and nutrient depletion. Here we identify in mice a previously unrecognized role
      for leptin and a population of leptin-regulated neurons that modulate the CRR to
      meet these challenges. Hypoglycemia activates neurons of the parabrachial nucleus
      (PBN) that coexpress leptin receptor (LepRb) and cholecystokinin (CCK) (PBN
      LepRb(CCK) neurons), which project to the ventromedial hypothalamic nucleus.
      Leptin inhibits these cells, and Cck(cre)-mediated ablation of LepRb enhances the
      CRR. Inhibition of PBN LepRb cells blunts the CRR, whereas their activation
      mimics the CRR in a CCK-dependent manner. PBN LepRb(CCK) neurons are a crucial
      component of the CRR system and may be a therapeutic target in hypoglycemia. 

PMID- 25383909
TI  - PrevenaTM, negative pressure wound therapy applied to closed Pfannenstiel
      incisions at time of caesarean section in patients deemed at high risk for wound
      infection.
AB  - The aim of our retrospective study is to report on our experience using the
      PrevenaTM wound system in obese patients undergoing caesarean section delivery. A
      total of 26 cases were identified from July 2012 to October 2013. The median BMI
      of these women was 45.3 kg/m(2). Elective caesarean sections were performed in 20
      women (77%). There were four cases (15%) of superficial dehiscence. Factors
      associated with wound breakdown were wound infection (p = 0.03), increasing BMI
      (p < 0.001) and emergency LSCS (p = 0.04). In a logistic regression model the
      presence of infection was the only factor which remained associated with wound
      breakdown. Wound disruption is a major cause of morbidity following caesarean
      section in morbidly obese patients. The wound complication rate in our experience
      was low with the PrevenaTM dressing with no cases of sheath dehiscence, and no
      patient required a second operation. The presence of infection is the most
      important factor in wound breakdown and should be the focus for management
      protocols. 

PMID- 25383912
TI  - Small-molecule detection in thiol-yne nanocomposites via surface-enhanced Raman
      spectroscopy.
AB  - Surface-enhanced Raman spectroscopy (SERS) is generally performed on planar
      surfaces, which can be difficult to prepare and may limit the interaction of the
      sensing surface with targets in large volume samples. We propose that
      nanocomposite materials can be configured that both include SERS probes and
      provide a high surface area-to-volume format, i.e., fibers. Thiol-yne
      nanocomposite films and fibers were fabricated using exposure to long-wave
      ultraviolet light after the inclusion of gold nanoparticles (AuNPs)
      functionalized with thiophenol. A SERS response was observed that was
      proportional to the aggregation of the AuNPs within the polymers and the amount
      of thiophenol present. Overall, this proof-of-concept fabrication of SERS active
      polymers indicated that thiol-yne nanocomposites may be useful as durable film or
      fiber SERS probes. Properties of the nanocomposites were evaluated using various
      techniques including UV-vis spectroscopy, MU-Raman spectroscopy, dynamic
      mechanical analysis, differential scanning calorimetry, thermogravimetric
      analysis, and transmission electron microscopy. 

PMID- 25383910
TI  - A stationary wavelet entropy-based clustering approach accurately predicts gene
      expression.
AB  - Studying epigenetic landscapes is important to understand the condition for gene
      regulation. Clustering is a useful approach to study epigenetic landscapes by
      grouping genes based on their epigenetic conditions. However, classical
      clustering approaches that often use a representative value of the signals in a
      fixed-sized window do not fully use the information written in the epigenetic
      landscapes. Clustering approaches to maximize the information of the epigenetic
      signals are necessary for better understanding gene regulatory environments. For
      effective clustering of multidimensional epigenetic signals, we developed a
      method called Dewer, which uses the entropy of stationary wavelet of epigenetic
      signals inside enriched regions for gene clustering. Interestingly, the gene
      expression levels were highly correlated with the entropy levels of epigenetic
      signals. Dewer separates genes better than a window-based approach in the
      assessment using gene expression and achieved a correlation coefficient above 0.9
      without using any training procedure. Our results show that the changes of the
      epigenetic signals are useful to study gene regulation. 

PMID- 25383913
TI  - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the direct
      detection of 2-monochloropropanediol (2-MCPD) esters in edible oils.
AB  - A new analytical method has been developed and validated for the detection and
      quantification of 2-monochloropropanediol (2-MCPD) esters in edible oils. The
      target compounds are potentially carcinogenic contaminants formed during the
      processing of edible oils. As the 2-MCPD esters that occur most frequently in
      refined edible oils were not commercially available, standards were synthesized
      with identity and purity (95+%) confirmed by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and (1)H NMR. Target analytes are separated from edible
      oil matrices using a two-step solid-phase extraction (SPE) procedure. The
      extracts are then analyzed using LC-MS/MS with electrospray ionization (ESI). The
      method has been validated for 11 2-MCPD diesters and 3 2-MCPD monoesters in
      soybean oil, olive oil, and palm oil using an external calibration curve. The
      ranges of average recoveries and relative standard deviations (RSD) across the
      three oil matrices at three spiking concentrations are 79-106% (3-13% RSD) for
      the 2-MCPD diesters and 72-108% (4-17% RSD) for the 2-MCPD monoesters, with
      limits of quantitation at or below 30 ng/g for the diesters and 90 ng/g for the
      monoesters. 

PMID- 25383914
TI  - Rhodium(III)-catalyzed olefinic C-H alkynylation of acrylamides using tosyl-imide
      as directing group.
AB  - The Rh(III)-catalyzed C-H alkynylation of acrylamide derivative is realized using
      a hypervalent alkynyl iodine reagent. The use of a weakly coordinating directing
      group proved to be of critical importance. This reaction displays broad
      functional group tolerance and high efficiency, which opens a new synthetic
      pathway to access functionalized 1,3-enyne skeletons. 

PMID- 25383915
TI  - Discovery and optimization of 4,5-diarylisoxazoles as potent dual inhibitors of
      pyruvate dehydrogenase kinase and heat shock protein 90.
AB  - Upregulation of pyruvate dehydrogenase kinase (PDHK) has been observed in a
      variety of cancers. Inhibition of PDHK offers an attractive opportunity for the
      development of novel cancer therapies. To obtain novel PDHK inhibitors, we took
      advantage of the homology of the ATP-binding pocket between Heat Shock Protein 90
      (HSP90) and PDHK, and utilized 4,5-diarylisoxazole based HSP90 inhibitor for
      structural design. Our efforts led to the identification of 5k that inhibited
      PDHK1 with an IC50 value of 17 nM, which, however, showed marginal cellular
      activity. Further structural optimization resulted in compound 11a with improved
      cellular activity which could effectively modulate the metabolic profile of
      cancer cells and lead to the inhibition of cancer cell proliferation, evidenced
      by the increased oxidative phosphorylation and decreased glycolysis and
      associated oxidative stress. Our results suggested 11a as an excellent lead
      compound and a favorable biological tool to further evaluate the therapeutic
      potential of PDHK and HSP90 dual inhibitors in the treatment of cancer. 

PMID- 25383916
TI  - A guide for developing plain-language and contextual summaries of systematic
      reviews in agri-food public health.
AB  - The application of systematic reviews is increasing in the agri-food public
      health sector to investigate the efficacy of policy-relevant interventions. In
      order to enhance the uptake and utility of these reviews for decision-making,
      there is a need to develop summary formats that are written in plain language and
      incorporate supporting contextual information. The objectives of this study were
      (1) to develop a guideline for summarizing systematic reviews in one- and three
      page formats, and (2) to apply the guideline on two published systematic reviews
      that investigated the efficacy of vaccination and targeted feed and water
      additives to reduce Salmonella colonization in broiler chickens. Both summary
      formats highlight the key systematic review results and implications in plain
      language. Three-page summaries also incorporated four categories of contextual
      information (cost, availability, practicality, and other stakeholder
      considerations) to complement the systematic review findings. We collected
      contextual information through structured rapid reviews of the peer-reviewed and
      gray literature and by conducting interviews with 12 topic specialists. The
      overall utility of the literature searches and interviews depended on the
      specific intervention topic and contextual category. In general, interviews with
      topic specialists were the most useful and efficient method of gathering
      contextual information. Preliminary evaluation with five end-users indicated
      positive feedback on the summary formats. We estimate that one-page summaries
      could be developed by trained science-to-policy professionals in 3-5 days, while
      three-page summaries would require additional resources and time (e.g., 2-4
      weeks). Therefore, one-page summaries are more suited for routine development,
      while three-page summaries could be developed for a more limited number of high
      priority reviews. The summary guideline offers a structured and transparent
      approach to support the utilization of systematic reviews in decision-making in
      this sector. Future research is necessary to evaluate the utility of these
      summary formats for a variety of end-users in different contexts.

PMID- 25383917
TI  - Electrochemical study of the catechol-modified chitosan system for clozapine
      treatment monitoring.
AB  - This work presents a thorough electrochemical and reliability analysis of a
      sensing scheme for the antipsychotic clozapine. We have previously demonstrated a
      novel detection approach for this redox-active drug, highly effective in
      schizophrenia treatment, based on a catechol-modified chitosan film. The
      biomaterial film enables amplification of the oxidative current generated by
      clozapine through redox cycling. Here, we study critical electrochemical and
      material aspects of the redox cycling system to overcome barriers in point-of
      care monitoring in complex biological samples. Specifically, we explore the
      electrochemical parameter space, showing that enhanced sensing performance
      depends on the presence of a reducing mediator as well as the electrochemical
      technique applied. These factors account for up to 1.75-fold and 2.47-fold signal
      enhancement, respectively. Looking at potential interferents, we illustrate that
      the redox cycling system allows for differentiation between selected redox-active
      species, clozapine's structurally largely analogous metabolite norclozapine as
      well as the representative catecholamine dopamine. Furthermore, we investigate
      material stability and fouling with reuse as well as storage. We find no evidence
      of film fouling due to clozapine; slow overall biomaterial degradation with
      successive use accounts for a 2.2% absolute signal loss and can be controlled
      for. Storage of the redox cycling system appears feasible over weeks when kept in
      solution with only 0.26%/day clozapine signal degradation, while ambient air
      exposure of three or more days reduces performance by 58%. This study not only
      advances our understanding of the catechol-modified chitosan system, but also
      further establishes the viability of applying it toward sensing clozapine in a
      clinical setting. Such point-of-care monitoring will allow for broader use of
      clozapine by increasing convenience to patients as well as medical professionals,
      thus improving the lives of people affected by schizophrenia through personalized
      medicine. 

PMID- 25383918
TI  - The role of verbal and pictorial information in multimodal incidental acquisition
      of foreign language vocabulary.
AB  - This study used eye tracking to investigate the allocation of attention to
      multimodal stimuli during an incidental learning situation, as well as its impact
      on subsequent explicit learning. Participants were exposed to foreign language
      (FL) auditory words on their own, in conjunction with written native language
      (NL) translations, or with both written NL translations and pictures. Incidental
      acquisition of FL words was assessed the following day through an explicit
      learning task where participants learned to recognize translation equivalents, as
      well as one week later through recall and translation recognition tests. Results
      showed higher accuracy scores in the explicit learning task for FL words
      presented with meaning during incidental learning, whether written meaning or
      both written meaning and picture, than for FL words presented auditorily only.
      However, participants recalled significantly more FL words after a week delay if
      they had been presented with a picture during incidental learning. In addition,
      the time spent looking at the pictures during incidental learning significantly
      predicted recognition and recall scores one week later. Overall, results
      demonstrated the impact of exposure to multimodal stimuli on subsequent explicit
      learning, as well as the important role that pictorial information can play in
      incidental vocabulary acquisition. 

PMID- 25383919
TI  - Amide groups switch selectivity: C-H trifluoromethylation of alpha,beta
      unsaturated amides and subsequent asymmetric transformation.
AB  - The first direct C-H beta-trifluoromethylation of unsubstituted or alpha-alkyl
      substituted alpha,beta-unsaturated carbonyl compounds under metal-free conditions
      was realized with excellent regio- and stereoselectivity as well as a very broad
      substrate scope. Both olefinic and allylic trifluoromethylation products are
      accessible with high selectivities by altering the substrate substitutions. The
      resultant olefinic products, namely (E)-beta-trifluoromethyl (CF3) alpha,beta
      unsaturated hydroxamic acid derivatives, served as acceptors in organocatalytic
      asymmetric Michael addition reactions to give hydroxamic acid derivatives bearing
      a chiral CF3-substituted stereocenter with high enantioselectivities. 

PMID- 25383920
TI  - Dual use of Department of Veterans Affairs and medicare benefits and use of test
      strips in veterans with type 2 diabetes mellitus.
AB  - IMPORTANCE: Self-monitoring of blood glucose is a costly component of care for
      diabetes mellitus, with unclear benefits for patients not taking insulin.
      Veterans with dual Department of Veterans Affairs (VA) and Medicare benefits have
      access to test strips through both systems, raising the potential for overuse.
      OBJECTIVES: To examine the patterns of test strip receipt among older veterans
      with diabetes and determine whether receipt of strips from dual health care
      systems is associated with overuse. DESIGN, SETTING, AND PARTICIPANTS: We
      performed a cross-sectional, retrospective cohort study using national VA
      administrative data linked to Medicare Parts A, B, and D claims for fiscal years
      2008 and 2009. A total of 363,996 community-dwelling veterans 65 years or older
      with diabetes who used the VA health care system and received test strips in
      fiscal year 2009 were included in the study. EXPOSURES: Receipt of test strips
      from the VA only, Medicare only, or both the VA and Medicare; covariates included
      sociodemographics, comorbidity, diabetes complications, and hemoglobin A1c level.
      MAIN OUTCOMES AND MEASURES: Quantity of test strips dispensed and overuse of test
      strips, defined as more than 1 strip per day (>365 strips per year) among those
      taking no diabetes medications, oral diabetes medications alone, or long-acting
      insulin without short-acting insulin or more than 4 strips per day (>1460 strips
      per year) among those taking short-acting insulin. RESULTS: Overall, 260,688
      older veterans (71.6%) with diabetes received strips from the VA only, 82,826
      (22.8%) from Medicare only, and 20,482 (5.6%) from the VA and Medicare. Veterans
      receiving strips from both the VA and Medicare received more strips (median, 600;
      interquartile range [IQR], 350-1000) than the Medicare only (median, 400; IQR,
      200-700) and VA only (median, 200; IQR, 100-500) groups (P < .001) and had
      substantially greater odds of overuse than the VA only group (55.4% vs 15.8%)
      (adjusted odds ratio [OR], 16.3; 95% CI, 14.6-18.1 for no medications; 55.3% vs
      6.0%; OR, 19.8; 95% CI, 18.9-20.8 for oral medications; 87.4% vs 65.5%; OR, 3.69;
      95% CI, 3.30-4.14 for long-acting insulin; and 32.8% vs 13.5%; OR, 3.24; 95% CI,
      3.05-3.45 for short-acting insulin). Patterns were similar when using more
      conservative thresholds of overuse. CONCLUSIONS AND RELEVANCE: Veterans who
      receive glucose test strips through both the VA and Medicare use more strips and
      are more likely to potentially overuse strips. These results illustrate the
      profound importance of understanding dual VA and Medicare coverage and are
      emblematic of waste and inefficiency.

PMID- 25383921
TI  - Thermodynamic study of rhodamine 123-calf thymus DNA interaction: determination
      of calorimetric enthalpy by optical melting study.
AB  - In this paper, the interaction of rhodamine123 (R123) with calf thymus DNA has
      been studied using molecular modeling and other biophysical methods like UV-vis
      spectroscopy, fluoremetry, optical melting, isothermal titration calorimetry, and
      circular dichroic studies. Results showed that the binding energy is about -6 to 
      8 kcal/mol, and the binding process is favored by both negative enthalpy change
      and positive entropy change. A new method to determine different thermodynamic
      properties like calorimetric enthalpy and heat capacity change has been
      introduced in this paper. The obtained data has been crossed-checked by other
      methods. After dissecting the free-energy contribution, it was observed that the
      binding was favored by both negative hydrophobic free energy and negative
      molecular free energy which compensated for the positive free energies due to the
      conformational change loss of rotational and transitional freedom of the DNA
      helix. 

PMID- 25383922
TI  - Spontaneous heparin-induced thrombocytopenia syndrome without any proximate
      heparin exposure, infection, or inflammatory condition: Atypical clinical
      features with heparin-dependent platelet activating antibodies.
AB  - Recent studies suggest that a thromboembolic disorder resembling heparin-induced
      thrombocytopenia (HIT), so-called spontaneous HIT syndrome, can occur in patients
      without any history of heparin exposure. It is likely due to anti-platelet factor
      4 (PF4)/polyanion antibodies induced by other polyanions, such as bacterial
      surfaces and nucleic acids. We describe an atypical case of spontaneous HIT
      syndrome. A 70-year-old man suddenly presented with acute cerebral sinus
      thrombosis (CST). Soon after the initiation of unfractionated heparin (UFH) for
      the treatment of CST, his platelet count fell precipitously and he developed deep
      vein thrombosis, a clinical picture consistent with rapid-onset HIT but without
      any proximate episodes of heparin exposure, infection, trauma, surgery, or other
      acute illness. Antigen assays and a washed platelet activation assay indicated
      that the patient already possessed anti-PF4/heparin IgG antibodies with heparin
      dependent platelet activation properties on admission. Cessation of UFH and
      initiation of argatroban resulted in prompt recovery of his platelet count
      without further thromboembolic events. We identified two similar cases in the
      literature. However, these patients do not meet the recently proposed criteria
      for spontaneous HIT syndrome. Even in atypical cases, however, inappropriate or
      delayed diagnosis of HIT appears to be associated with worse outcomes. We propose
      that these atypical cases should be included in the category of spontaneous HIT
      syndrome. 

PMID- 25383923
TI  - [Systematic reviews of biomedical literature: an introduction for busy
      clinicians].

PMID- 25383924
TI  - The accessory helix of complexin functions by stabilizing central helix secondary
      structure.
AB  - The presynaptic protein complexin (CPX) is a critical regulator of synaptic
      vesicle fusion, but the mechanisms underlying its regulatory effects are not well
      understood. Its highly conserved central helix (CH) directly binds the ternary
      SNARE complex and is required for all known CPX functions. The adjacent accessory
      helix (AH) is not conserved despite also playing an important role in CPX
      function, and numerous models for its mechanism have been proposed. We examined
      the impact of AH mutations and chimeras on CPX function in vivo and in vitro
      using C. elegans. The mouse AH fully restored function when substituted into worm
      CPX suggesting its mechanism is evolutionarily conserved. CPX inhibitory function
      was impaired when helix propagation into the CH was disrupted whereas replacing
      the AH with a non-native helical sequence restored CPX function. We propose that
      the AH operates by stabilizing CH secondary structure rather than through protein
      or lipid interactions.

PMID- 25383925
TI  - Evolving a 24-hr oscillator in budding yeast.
AB  - We asked how a new, complex trait evolves by selecting for diurnal oscillations
      in the budding yeast, Saccharomyces cerevisiae. We expressed yellow fluorescent
      protein (YFP) from a yeast promoter and selected for a regular alternation
      between low and high fluorescence over a 24-hr period. This selection produced
      changes in cell adhesion rather than YFP expression: clonal populations
      oscillated between single cells and multicellular clumps. The oscillations are
      not a response to environmental cues and continue for at least three cycles in a
      constant environment. We identified eight putative causative mutations in one
      clone and recreated the evolved phenotype in the ancestral strain. The mutated
      genes lack obvious relationships to each other, but multiple lineages change from
      the haploid to the diploid pattern of gene expression. We show that a novel,
      complex phenotype can evolve by small sets of mutations in genes whose molecular
      functions appear to be unrelated to each other.

PMID- 25383927
TI  - [The challenges of demographic change - mental illnesses today and tomorrow].

PMID- 25383928
TI  - [The Ontario Domestic Assault Risk Assessment (ODARA) - Validity und authorised
      German translation of an intimate partner violence screening tool].
AB  - On average one third of all women are victimised by intimate partner violence at
      least once in their life. Many women are affected repeatedly. To efficiently
      reduce the risk of repeated violence a reliable and valid risk assessment is
      needed. To date several risk assessment tools have been published in the field of
      intimate partner violence. There is a strong demand for such tools to be
      applicable by a wider range of practitioners (e.g., police officers, hospital and
      victim services' staff) to reliably assess cases of intimate partner violence and
      recommend further interventions. By developing the Ontario Domestic Assault Risk
      Assessment (ODARA) it was the authors' aim to provide a brief risk assessment
      tool which can be scored on the basis of only few and easily collectable
      information and which efficiently discriminates between low-risk and high-risk
      offenders of intimate partner violence. Previous replication studies found
      moderate to good and on average higher power of discrimination of the ODARA
      compared to other risk assessment tools in the field. However, for the German
      speaking countries robust findings are still lacking. In the present publication
      a scientific and authorised translation of the ODARA is provided.

PMID- 25383926
TI  - Structural basis of diverse membrane target recognitions by ankyrins.
AB  - Ankyrin adaptors together with their spectrin partners coordinate diverse ion
      channels and cell adhesion molecules within plasma membrane domains and thereby
      promote physiological activities including fast signaling in the heart and
      nervous system. Ankyrins specifically bind to numerous membrane targets through
      their 24 ankyrin repeats (ANK repeats), although the mechanism for the facile and
      independent evolution of these interactions has not been resolved. Here we report
      the structures of ANK repeats in complex with an inhibitory segment from the C
      terminal regulatory domain and with a sodium channel Nav1.2 peptide,
      respectively, showing that the extended, extremely conserved inner groove
      spanning the entire ANK repeat solenoid contains multiple target binding sites
      capable of accommodating target proteins with very diverse sequences via
      combinatorial usage of these sites. These structures establish a framework for
      understanding the evolution of ankyrins' membrane targets, with implications for
      other proteins containing extended ANK repeat domains. 

PMID- 25383930
TI  - [The new payment system in psychiatry - do elderly people belong to the losers?
      An analysis on the basis of the VIPP1 data base].
AB  - The development of the lump-sum reimbursement System in psychiatry and
      psychosomatics (PEPP) (Klimke et al., 2014) is being negatively considered - also
      in gerontopsychiatry.Thus it is reasonable to make a timely analysis of the
      effects of PEPP on health-care structures. For this two analyses have been
      carried out. On the one hand the day mix index of elderly patients (> 64 years)
      was compared with that of younger ones (> 17 years, < 65 years). On the other
      hand younger and older were included in the analysis with regard to the available
      treatment minutes in exact daily classifications according to the PsychPV. It is
      seen that evaluation of the individual day was markedly higher for
      gerontopsychiatric patients not only in inpatient (difference > 0.1) but also in
      outpatient (difference > 0.07) setting. The exact daily classifications according
      to PsychPV, however, were markedly poorer for the elderly patients. Thus, on the
      basis of routine data of VIPP projects, a clear change can be seen in favour of
      the elderly patient under PEPP conditions as compared to financing according to
      PsychPV. However, concern remains that the ageing population and modernisation of
      therapy are not being sufficiently taken into account. The new reimbursement
      system merely regulates the distribution of available resources; if these
      resources are too low nothing will change by the PEPP-System.

PMID- 25383931
TI  - [DemTect 40- and DemTect 80+: New scoring routines for these age groups].
AB  - The DemTect, a frequently used cognitive screening tool for the German-speaking
      population, has been proven to be age-, but not education-dependent. To date,
      scoring routines for persons under and over 60 years of age have been available.
      In order to describe the age-effect more specifically, the DemTect was
      administered to persons under 40 (n = 105; median 33 years [18 - 39]) and over 80
      years of age [n = 68; median 83 years [80 - 93}). After transformation of the raw
      scores, which are based on the mean and standard deviation of the respective
      reference group, an adequate attribution of scores could be achieved and no
      differences between the groups can be observed in the total score or the subtest
      scores. The median of the transformed total score was 16 [5 - 18] for the younger
      and 15 [5 - 18] for the older age group. The new scoring routines supplement the
      scoring procedures of the DemTect for these age groups.

PMID- 25383932
TI  - [Pediatric bipolar disorder - case report of a bipolar patient with disease onset
      in childhood and adolescence: implications for diagnosis and therapy].
AB  - In recent years, intense controversies have evolved about the existence and exact
      diagnostic criteria of pediatric bipolar affective disorder. The present study
      aims to discuss pediatric bipolar affective disorder based on the current
      literature focussing on the diagnostic prospects. Based on a case study, a
      process of bipolar disorder developed in childhood is depicted exemplarily.
      Because of the high comorbidity and overlapping symptoms of paediatric bipolar
      affective disorder and other psychiatric disorders, the major impact of the
      differential diagnosis has to be stressed. An early diagnosis and the treatment
      possibilities are discussed.

PMID- 25383933
TI  - [Diagnosis of affective disorders in DSM-5: changes and controversies].

PMID- 25383934
TI  - [Professional association of German neurologists].

PMID- 25383935
TI  - Poly(vinylidene fluoride)-based flexible and lightweight materials for
      attenuating microwave radiations.
AB  - Two unique materials were developed, like graphene oxide (GO) sheets covalently
      grafted on to barium titanate (BT) nanoparticles and cobalt nanowires (Co-NWs),
      to attenuate the electromagnetic (EM) radiations in poly(vinylidene fluoride)
      (PVDF)-based composites. The rationale behind using either a ferroelectric or a
      ferromagnetic material in combination with intrinsically conducting nanoparticles
      (multiwall carbon nanotubes, CNTs), is to induce both electrical and magnetic
      dipoles in the system. Two key properties, namely, enhanced dielectric constant
      and magnetic permeability, were determined. PVDF/BT-GO composites exhibited
      higher dielectric constant compared to PVDF/BT and PVDF/GO composites. Co-NWs,
      which were synthesized by electrodeposition, exhibited saturation magnetization
      (Ms) of 40 emu/g and coercivity (Hc) of 300 G. Three phase hybrid composites were
      prepared by mixing CNTs with either BT-GO or Co-NWs in PVDF by solution blending.
      These nanoparticles showed high electrical conductivity and significant
      attenuation of EM radiations both in the X-band and in the Ku-band frequency. In
      addition, BT-GO/CNT and Co-NWs/CNT particles also enhanced the thermal
      conductivity of PVDF by ca. 8.7- and 9.3-fold in striking contrast to neat PVDF.
      This study open new avenues to design flexible and lightweight electromagnetic
      interference shielding materials by careful selection of functional
      nanoparticles. 

PMID- 25383929
TI  - [Stroke occurence in Germany - on the comparability of insurance data and
      registry-based data].
AB  - PURPOSE: This article presents epidemiological data regarding stroke frequency in
      Germany based on nationwide statutory health insurance data (Deutsche BKK) and
      aims to analyse them in the context of current research. The comparability of the
      most important resources of stroke frequency data - stroke registers, DRG data
      and insurance data - is initially discussed in order to assess the presented data
      adequately. METHODS: The study cohort comes from a population of about 1 000 000
      people insured with BKK and consists of all persons who were treated for a stroke
      in an acute care hospital in 2007 (n = 4,843). Data were subjected to statistical
      secondary analysis including uni- and bivariate statistics and t tests. Reference
      studies for the observation period include data from GEK and AOK health
      insurances, from quality assurances Hessen and Bayern, from the ADSR, and
      hospital DRG data. The different study types are compared regarding their
      inclusion/exclusion criteria and the resulting effects on reported prevalences.
      RESULTS: Different inclusion criteria and accordingly different
      operationalisations of "stroke" impede the comparability of existing German data
      resources regarding stroke. The inclusion of TIA, non-traumatic subdural
      haemorrhage (I62), and the frequency of unspecified strokes (I64) is especially
      inconsistent. In addition, recurrent strokes and the definition of first-ever
      strokes are treated differently. The study cohort reveals no major discrepancies
      regarding aetiological subgroups compared to previous results, only the
      percentage of women (60.3 %) seems exceptionally high. CONCLUSIONS: The gender
      effect is attributed to the BKK member structure, and especially the high
      proportion of women in the older age groups. Discussion of stroke frequency in
      Germany needs to take structural differences between study types into account.
      There are two vulnerable groups that tend to be underrepresented: TIA patients
      with a high risk of recurrent strokes, and high-risk patients who have already
      had a stroke and are care-dependent, which are often unspecifically coded. In the
      future, study designs should include the whole range of stroke coding, thus
      enabling differentiated analyses.

PMID- 25383936
TI  - Electron-induced conversion of silylones to six-membered cyclic silylenes.
AB  - A silicon atom in the zero oxidation state stabilized by two carbene ligands is
      known as siladicarbene (silylone). There are two pairs of electrons on the
      silicon atom in silylone. This was recently confirmed by both experimental and
      theoretical charge density investigations. The silylone is stable up to 195 
      degrees C in an inert atmosphere. However, a substoichiometric amount (33 mol%)
      of potassium metal triggers the activation of the unsaturated C:Si:C backbone,
      leading to a selective reaction with a tertiary C-H bond in an atom-economical
      approach to form a six-membered cyclic silylene with three-coordinate silicon
      atom. Cyclic voltammetry shows that this reaction proceeds via the formation of a
      silylone radical anion intermediate, which is further confirmed by EPR
      spectroscopy. 

PMID- 25383937
TI  - Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with
      cystic fibrosis.
AB  - BACKGROUND: Respiratory tract infection with Pseudomonas aeruginosa occurs in
      most people with cystic fibrosis. Once chronic infection is established,
      Pseudomonas aeruginosa is virtually impossible to eradicate and is associated
      with increased mortality and morbidity. Early infection may be easier to
      eradicate.This is an update of a Cochrane review first published in 2003, and
      previously updated in 2006 and 2009. OBJECTIVES: To determine whether antibiotic
      treatment of early Pseudomonas aeruginosa infection in children and adults with
      cystic fibrosis eradicates the organism, delays the onset of chronic infection,
      and results in clinical improvement. To evaluate whether there is evidence that a
      particular antibiotic strategy is superior to or more cost-effective than other
      strategies and to compare the adverse effects of different antibiotic strategies
      (including respiratory infection with other micro-organisms). SEARCH METHODS: We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register
      comprising references identified from comprehensive electronic database searches
      and handsearches of relevant journals and abstract books of conference
      proceedings.Most recent search: 08 September 2014. SELECTION CRITERIA: We
      included randomised controlled trials of people with cystic fibrosis, in whom
      Pseudomonas aeruginosa had recently been isolated from respiratory secretions. We
      compared combinations of inhaled, oral or intravenous antibiotics with placebo,
      usual treatment or other combinations of inhaled, oral or intravenous
      antibiotics. We excluded non-randomised trials, cross-over trials, and those
      utilising historical controls. DATA COLLECTION AND ANALYSIS: Both authors
      independently selected trials, assessed risk of bias and extracted data. MAIN
      RESULTS: The search identified 49 trials; seven trials (744 participants) with a
      duration between 28 days and 27 months were eligible for inclusion. Three of the
      trials are over 10 years old and their results may be less applicable today given
      the changes in standard treatment. Some of the trials had low numbers of
      participants and most had relatively short follow-up periods; however, there was
      generally a low risk of bias from missing data. In most trials it was difficult
      to blind participants and clinicians to treatment given the interventions and
      comparators used. Two trials were supported by the manufacturers of the
      antibiotic used.Evidence from two trials (38 participants) at the two-month time
      point showed treatment of early Pseudomonas aeruginosa infection with inhaled
      tobramycin results in microbiological eradication of the organism from
      respiratory secretions more often than placebo, odds ratio 0.15 (95% confidence
      interval 0.03 to 0.65) and data from one of these trials, with longer follow up,
      suggested that this effect may persist for up to 12 months.One randomised
      controlled trial (26 participants) compared oral ciprofloxacin and nebulised
      colistin versus usual treatment. Results after two years suggested treatment of
      early infection results in microbiological eradication of Pseudomonas aeruginosa
      more often than no anti-pseudomonal treatment, odds ratio 0.12 (95% confidence
      interval 0.02 to 0.79).One trial comparing 28 days to 56 days treatment with
      nebulised tobramycin solution for inhalation in 88 participants showed that both
      treatments were effective and well-tolerated, with no notable additional
      improvement with longer over shorter duration of therapy. However, this trial was
      not powered to detect non-inferiority or equivalence .A trial of oral
      ciprofloxacin with inhaled colistin versus nebulised tobramycin solution for
      inhalation alone (223 participants) failed to show a difference between the two
      strategies, although it was underpowered to show this. A further trial of inhaled
      colistin with oral ciprofloxacin versus nebulised tobramycin solution for
      inhalation with oral ciprofloxacin also showed no superiority of the former, with
      increased isolation of Stenotrophomonas maltophilia in both groups.A recent,
      large trial in 306 children aged between one and 12 years compared cycled
      nebulised tobramycin solution for inhalation to culture-based therapy and also
      ciprofloxacin to placebo. The primary analysis showed no difference in time to
      pulmonary exacerbation or proportion of Pseudomonas aeruginosa positive cultures.
      An analysis performed in this review (not adjusted for age) showed fewer
      participants in the cycled therapy group with one or more isolates of Pseudomonas
      aeruginosa, odds ratio 0.51 (95% CI 0.31 to 0.28). AUTHORS' CONCLUSIONS: We found
      that nebulised antibiotics, alone or in combination with oral antibiotics, were
      better than no treatment for early infection with Pseudomonas aeruginosa.
      Eradication may be sustained for up to two years. There is insufficient evidence
      to determine whether antibiotic strategies for the eradication of early
      Pseudomonas aeruginosa decrease mortality or morbidity, improve quality of life,
      or are associated with adverse effects compared to placebo or standard treatment.
      Four trials of two active treatments have failed to show differences in rates of
      eradication of Pseudomonas aeruginosa. There have been no published randomised
      controlled trials that investigate the efficacy of intravenous antibiotics to
      eradicate Pseudomonas aeruginosa in cystic fibrosis. Overall, there is still
      insufficient evidence from this review to state which antibiotic strategy should
      be used for the eradication of early Pseudomonas aeruginosa infection in cystic
      fibrosis.

PMID- 25383938
TI  - Biochemical validation of the older Australian's food frequency questionnaire
      using carotenoids and vitamin E.
AB  - BACKGROUND: Validation of a food frequency questionnaire (FFQ) is important, as
      inaccurate and imprecise information may affect the association between dietary
      exposure and health outcomes. OBJECTIVE: This study assessed the validity of the
      Older Australian's FFQ against plasma carotenoids and Vitamin E. METHODS: A
      random subsample (n = 150) of 2420 participants in the Hunter Community Study,
      aged 55-85 years, were included. Correlations between crude and energy-adjusted
      FFQ estimates of carotenoids, Vitamin E, and fruit and vegetables with
      corresponding biomarkers were determined. Percentages of participants correctly
      classified in the same quartile, and in the same +/- 1 quartile, by the two
      methods were calculated. RESULTS: Significant correlations (P < 0.05) were
      observed for alpha-carotene (r = 0.26-0.28), beta-carotene (r = 0.21-0.25), and
      beta-cryptoxanthin (r = 0.21-0.23). Intakes of fruits and vegetables also showed
      similar correlations with these plasma carotenoids. Lycopene was only
      significantly correlated with fruit and vegetable intakes (r = 0.19-0.23). Weak
      correlations were observed for lutein + zeaxanthin (r = 0.12-0.16). For Vitamin
      E, significant correlation was observed for energy-adjusted FFQ estimate and
      biomarker (r = 0.20). More than 68% of individuals were correctly classified
      within the same or adjacent quartile, except for lutein + zeaxanthin. CONCLUSION:
      With the exception of lutein + zeaxanthin, the Older Australian's FFQ provides
      reasonable rankings for individuals according to their carotenoids, Vitamin E,
      fruit and vegetable intakes.

PMID- 25383939
TI  - Short-range interactions of concentrated proline in aqueous solution.
AB  - Molecular interactions for proline in a highly concentrated aqueous solution (up
      to 1:5 proline:water molecular ratio) have been investigated using a variety of
      experimental and computational techniques. Rather than the solution containing
      either small crystallites or large aggregates of proline, three-dimensional
      structural analysis reveals the presence of proline-proline dimers. These dimers
      appear to be formed by cyclic electrostatic interactions between CO2(-) and
      NH2(+) groups on neighboring proline molecules, which causes the ring motifs of
      proline to be roughly parallel to one another. In addition, water appears to
      aggregate around the electrostatic groups of the proline-proline dimers where it
      may in fact bridge these groups on different molecules. The observed short-range
      interactions for proline in solution may explain its function as a hydrotrope in
      vivo in which this observed dimerization might allow proline molecules to
      generate small pockets of a hydrophobic environment that can associate with
      nonpolar motifs of other molecules in solution. The results presented here
      emphasize the need for careful three-dimensional analysis to assess the short
      range order of highly concentrated solutions. 

PMID- 25383940
TI  - Effect of deregionalized care on mortality in very low-birth-weight infants with
      necrotizing enterocolitis.
AB  - IMPORTANCE: There has been a significant expansion in the number of low-level and
      midlevel neonatal intensive care units (NICUs) in recent decades. Infants with
      necrotizing enterocolitis represent a high-risk subgroup of the very low-birth
      weight (VLBW) (<1500 g) population that would benefit from focused
      regionalization. OBJECTIVES: To describe the current trend toward
      deregionalization and to test the hypothesis that infants with necrotizing
      enterocolitis represent a particularly high-risk subgroup of the VLBW population
      that would benefit from early identification, increased intensity of early
      management, and possible targeted triage to tertiary hospitals. DESIGN, SETTING,
      AND PARTICIPANTS: A retrospective cohort study was conducted of NICUs in
      California. We used data collected by the California Perinatal Quality Care
      Collaborative from 2005 to 2011 to assess mortality rates among a population
      based sample of 30 566 VLBW infants, 1879 with necrotizing enterocolitis,
      according to the level of care and VLBW case volume at the hospital of birth.
      EXPOSURES: Level and volume of neonatal intensive care at the hospital of birth.
      MAIN OUTCOMES AND MEASURES: In-hospital mortality. RESULTS: There was a
      persistent trend toward deregionalization during the study period and mortality
      rates varied according to the level of care. High-level, high-volume (level IIIB
      with >100 VLBW cases per year and level IIIC) hospitals achieved the lowest risk
      adjusted mortality. Infants with necrotizing enterocolitis born into midlevel
      hospitals (low-volume level IIIB and level IIIA NICUs) had odds of death ranging
      from 1.42 (95% CI, 1.08-1.87) to 1.51 (95% CI, 1.05-2.15, respectively). In the
      final year of the study, just 28.6% of the infants with necrotizing enterocolitis
      were born into high-level, high-volume hospitals. For infants born into lower
      level centers, transfer to a higher level of care frequently occurred well into
      the third week of life. CONCLUSIONS AND RELEVANCE: These findings represent an
      immediate opportunity for local quality improvement initiatives and potential
      impetus for the regionalization of important NICU resources.

PMID- 25383941
TI  - Patient factors predisposing to complications following laparoscopic surgery for
      colorectal cancers.
AB  - The aim of this study was to clarify patient factors contributing to
      complications after laparoscopic surgery for colorectal cancers. A total of 333
      colorectal cancer patients who underwent laparoscopic colorectal resection
      between January 2007 and December 2012 were enrolled. The association between
      patient factors and the incidence of complications were analyzed. Postoperative
      complications were divided into 2 categories: infectious complications and
      noninfectious complications. The overall complication rate was 13% and mortality
      rate 0%. Multivariate analysis showed that body mass index >25 kg/m [odds ratio
      (OR)=3.02, P=0.0254] and tumor location (right colon cancer/rectal cancer:
      OR=0.11, P=0.0083) were risk factors for infectious complications; in addition,
      male sex (OR=3.91, P=0.0102) and cancer stage (stage 2/stage 4: OR=0.17,
      P=0.0247) were risk factors for noninfectious complications. This study shows
      that different patient factors are associated with the risk of different types of
      complications. 

PMID- 25383942
TI  - Laparoscopic Spigelian Hernia Repair: A Series of 40 Patients.
AB  - Spigelian hernias are a rare abdominal wall hernia. The aim of this study was to
      assess the efficacy and outcomes of patients who underwent a laparoscopic
      spigelian hernia repair. A retrospective study was performed reviewing all
      patients who had a laparoscopic spigelian hernia repair. We assessed the success
      of the procedure including conversion rates, postoperative morbidities, and
      recurrence rates. Forty patents had a laparoscopic repair. Two thirds (n=25) had
      an intraperitoneal repair. There was no conversion to open repair. Four patients
      had postoperative morbidities. At 6-month follow-up all patients were pain free,
      with 1 recurrence. There is considerable evidence supporting the opinion that
      laparoscopic repair offers excellent outcomes. This report is the largest series
      to date, and we advocate that this approach should become the standard of care. 

PMID- 25383943
TI  - Supramolecular assembly-induced yellow emission of 9,10-distyrylanthracene
      bridged bis(pillar[5]arene)s.
AB  - 9,10-Distyrylanthracene has been introduced to bridge two pillarenes to form a
      dimeric host, which can assemble into a linear supramolecular polymer upon
      cooperatively binding to a neutral guest linker, exhibiting yellow fluorescence
      emission in solution and solid states. 

PMID- 25383944
TI  - The incidence of DNR documentation in patients referred for palliative
      radiotherapy in the Rapid Response Radiotherapy Program.

PMID- 25383946
TI  - A preliminary study on Oxya fuscovittata (Marschall) as an alternative nutrient
      supplement in the diets of Poecillia sphenops (Valenciennes).
AB  - Growth of the ornamental fish industry is being hindered by the scarcity of low
      cost feed; hence alternative protein supplements should be explored. In this
      context the present study aims to evaluate whether the grasshopper Oxya
      fuscovittata could be used as a supplement for fish meal in the diets of
      Poecillia sphenops, which is one of the most common ornamental fishes worldwide.
      The present work is divided into three phases: In the first phase proximate
      composition of the grasshopper is obtained and five diets are prepared where fish
      meal is gradually replaced by Oxya meal and named as control, D1, D2, D3 and D4.
      All the diets are formulated on iso-nitrogenous basis where the protein
      percentage is fixed at 400 g/kg. The second phase deals with feeding trial and in
      the third phase all the data of the feeding trial are subjected to a linear
      model. The feeding trial shows that the control, D1 and D2 fed fishes have almost
      similar results. The linear model proves that the variation in the indices are
      mainly due to replacement of fish meal by Oxya meal, not due to the variations of
      rice husk and mustard oil cake that are also used to formulate the diets of the
      present study. From the results two Oxya supplemented diets, i.e. D1 and D2 are
      proved to be almost equivalent to the control diet. Hence it is concluded that
      Oxya meal is able to replace 25% to 50% of fish meal from the diets of P.
      sphenops. 

PMID- 25383945
TI  - A novel mutation in the RPE65 gene causing Leber congenital amaurosis and its
      transcriptional expression in vitro.
AB  - The retinal pigment epithelium-specific 65 kDa protein is an isomerase encoded by
      the RPE65 gene (MIM 180069) that is responsible for an essential enzymatic step
      required for the function of the visual cycle. Mutations in the RPE65 gene cause
      not only subtype II of Leber congenital amaurosis (LCA) but also early-onset
      severe retinal dystrophy (EOSRD). This study aims to investigate a Chinese case
      diagnosed as EOSRD and to characterize the polymorphisms of the RPE65 gene. A
      seven-year-old girl with clinical symptoms of EOSRD and her parents were
      recruited into this study. Ophthalmologic examinations, including best-corrected
      visual acuity, slit-lamp, Optical coherence tomography (OCT), and fundus
      examination with dilated pupils, were performed to determine the clinical
      characteristics of the whole family. We amplified and sequenced the entire coding
      region and adjacent intronic sequences of the coding regions of the RPE65 gene
      for the whole family to explore the possible mutation. Our results demonstrate
      that the patient exhibited the typical clinically features of EOSRD. Her
      bilateral decimal visual acuity was 0.3 and 0.4 in the left and right eyes,
      respectively. Spectral-domain optical coherence tomography (SD-OCT) was used to
      assess the retinal stratification for the whole family. All together, we
      identified four mutations within the RPE65 gene (c.1056G>A, c.1243+2T>A,
      c.1338+20A>C and c.1590C>A) in the patient. Among the four mutations, c.1056G>A
      and c.1338+20A>C had been reported previously and another two were found for the
      first time in this study. Her mother also carried the novel mutation
      (c.1243+2T>A). Either a single or a compound heterozygous or a homozygous one
      mutation is expected to cause EOSRD because mutations of RPE65 gene usually cause
      an autosomal recessive disease. Therefore, we speculate that the c.1590C>A
      mutation together with the c.1243+2T>A mutation may cause the patient's
      phenotype. 

PMID- 25383947
TI  - Detecting, visualizing, and measuring gold nanoparticle chirality using helical
      pitch measurements in nematic liquid crystal phases.
AB  - Chirality at the nanoscale, or more precisely, the chirality or chiroptical
      effects of chiral ligand-capped metal nanoparticles (NPs) is an intriguing and
      rapidly evolving field in nanomaterial research with promising applications in
      catalysis, metamaterials, and chiral sensing. The aim of this work was to seek
      out a system that not only allows the detection and understanding of NP chirality
      but also permits visualization of the extent of chirality transfer to a
      surrounding medium. The nematic liquid crystal phase is an ideal candidate,
      displaying characteristic defect texture changes upon doping with chiral
      additives. To test this, we synthesized chiral cholesterol-capped gold NPs and
      prepared well-dispersed mixtures in two nematic liquid crystal hosts. Induced
      circular dichroism spectropolarimetry and polarized light optical microscopy
      revealed that all three gold NPs induce chiral nematic phases, and that those
      synthesized in the presence of a chiral bias (disulfide) are more powerful chiral
      inducers than those where the NP was formed in the absence of a chiral bias
      (prepared by conjugation of a chiral silane to preformed NPs). Helical pitch data
      here visually show a clear dependence on the NP size and the number of chiral
      ligands bound to the NP surface, thereby supporting earlier experimental and
      theoretical data that smaller metal NPs made in the presence of a chiral bias are
      stronger chiral inducers. 

PMID- 25383948
TI  - Transient exposure to ethanol during zebrafish embryogenesis results in defects
      in neuronal differentiation: an alternative model system to study FASD.
AB  - BACKGROUND: The exposure of the human embryo to ethanol results in a spectrum of
      disorders involving multiple organ systems, including the impairment of the
      development of the central nervous system (CNS). In spite of the importance for
      human health, the molecular basis of prenatal ethanol exposure remains poorly
      understood, mainly to the difficulty of sample collection. Zebrafish is now
      emerging as a powerful organism for the modeling and the study of human diseases.
      In this work, we have assessed the sensitivity of specific subsets of neurons to
      ethanol exposure during embryogenesis and we have visualized the sensitive
      embryonic developmental periods for specific neuronal groups by the use of
      different transgenic zebrafish lines. METHODOLOGY/PRINCIPAL FINDINGS: In order to
      evaluate the teratogenic effects of acute ethanol exposure, we exposed zebrafish
      embryos to ethanol in a given time window and analyzed the effects in
      neurogenesis, neuronal differentiation and brain patterning. Zebrafish larvae
      exposed to ethanol displayed small eyes and/or a reduction of the body length,
      phenotypical features similar to the observed in children with prenatal exposure
      to ethanol. When neuronal populations were analyzed, we observed a clear
      reduction in the number of differentiated neurons in the spinal cord upon ethanol
      exposure. There was a decrease in the population of sensory neurons mainly due to
      a decrease in cell proliferation and subsequent apoptosis during neuronal
      differentiation, with no effect in motoneuron specification. CONCLUSION: Our
      investigation highlights that transient exposure to ethanol during early
      embryonic development affects neuronal differentiation although does not result
      in defects in early neurogenesis. These results establish the use of zebrafish
      embryos as an alternative research model to elucidate the molecular mechanism(s)
      of ethanol-induced developmental toxicity at very early stages of embryonic
      development.

PMID- 25383950
TI  - The clinical utility of informants' appraisals on prospective and retrospective
      memory in patients with early Alzheimer's disease.
AB  - Increasing studies suggest the importance of including prospective memory
      measures in clinical evaluation of dementia due to its sensitivity and functional
      relevance. The Prospective and Retrospective Memory Questionnaire (PRQM) is
      originally a self-rated memory inventory that offers a direct comparison between
      prospective and episodic memory. However, the informant's report has been
      recognized as a more valid source of cognitive complaints. We thus aimed to
      examine the validity of the informant-rated form of the PRMQ in assessing memory
      function of the patients and in detecting individuals with early dementia. The
      informants of 140 neurological outpatients with memory complaints completed the
      Taiwan version of the PRMQ. Tests of prospective memory, short-term memory, and
      general cognitive ability were also administered to non-demented participants and
      patients with early stages of Alzheimer's disease (AD). Results showed
      significant relationships between the PRMQ ratings and objective cognitive
      measures, and showed that higher ratings on the PRMQ were associated with
      increasing odds of greater dementia severity. Receiver operative characteristic
      (ROC) curves showed an adequate ability of the PRMQ to identify patients with
      dementia (93% sensitivity and 84% specificity). Hierarchical regression revealed
      that the PRMQ has additional explanatory power for dementia status after
      controlling for age, education and objective memory test results, and that the
      prospective memory subscale owns predictive value for dementia beyond the
      retrospective memory subscale. The present study demonstrated the external
      validity and diagnostic value of informants' evaluation of their respective
      patients' prospective and retrospective memory functioning, and highlighted the
      important role of prospective memory in early dementia detection. The proxy
      version of the PRMQ is a useful tool that captures prospective and episodic
      memory problems in patients with early AD, in combination with standardized
      cognitive testing. 

PMID- 25383949
TI  - TCR triggering by pMHC ligands tethered on surfaces via poly(ethylene glycol)
      depends on polymer length.
AB  - Antigen recognition by T cells relies on the interaction between T cell receptor
      (TCR) and peptide-major histocompatibility complex (pMHC) at the interface
      between the T cell and the antigen presenting cell (APC). The pMHC-TCR
      interaction is two-dimensional (2D), in that both the ligand and receptor are
      membrane-anchored and their movement is limited to 2D diffusion. The 2D nature of
      the interaction is critical for the ability of pMHC ligands to trigger TCR. The
      exact properties of the 2D pMHC-TCR interaction that enable TCR triggering,
      however, are not fully understood. Here, we altered the 2D pMHC-TCR interaction
      by tethering pMHC ligands to a rigid plastic surface with flexible poly(ethylene
      glycol) (PEG) polymers of different lengths, thereby gradually increasing the
      ligands' range of motion in the third dimension. We found that pMHC ligands
      tethered by PEG linkers with long contour length were capable of activating T
      cells. Shorter PEG linkers, however, triggered TCR more efficiently. Molecular
      dynamics simulation suggested that shorter PEGs exhibit faster TCR binding on
      rates and off-rates. Our findings indicate that TCR signaling can be triggered by
      surface-tethered pMHC ligands within a defined 3D range of motion, and that fast
      binding rates lead to higher TCR triggering efficiency. These observations are
      consistent with a model of TCR triggering that incorporates the dynamic
      interaction between T cell and antigen-presenting cell. 

PMID- 25383951
TI  - Asbestos exposure, pleural plaques, and the risk of death from lung cancer.
AB  - RATIONALE: Although asbestos is a well-known lung carcinogen, the pleural plaque
      lung cancer link remains controversial. OBJECTIVES: This study was designed to
      examine this link in asbestos-exposed workers. METHODS: A 6-year follow-up was
      conducted to study lung cancer mortality in the 5,402 male subjects participating
      in an asbestos-related disease screening program conducted from October 2003 to
      December 2005 in four French regions. Chest computed tomography (CT) scan was
      performed in all subjects with randomized, independent, double reading of CT
      scans focusing on benign asbestos-related abnormalities. Cox model survival
      regression analysis was used to model lung cancer mortality according to the
      presence of pleural plaques, with age as the main time variable, adjusting for
      smoking and asbestos cumulative exposure index. All statistical tests were two
      sided. MEASUREMENTS AND MAIN RESULTS: Thirty-six deaths from lung cancer were
      recorded. Lung cancer mortality was significantly associated with pleural plaques
      in the follow-up study in terms of both the unadjusted hazard ratio of 2.91 (95%
      confidence interval = 1.49-5.70) and the adjusted hazard ratio of 2.41 (95%
      confidence interval = 1.21-4.85) after adjustment for smoking and asbestos
      cumulative exposure index. CONCLUSIONS: Pleural plaques may be an independent
      risk factor for lung cancer death in asbestos-exposed workers and could be used
      as an additional criterion in the definition of high-risk populations eligible
      for CT screening.

PMID- 25383956
TI  - Introducing a large polar tetragonal distortion into Ba-doped BiFeO3 by low
      temperature fluorination.
AB  - This article reports on the synthesis and crystallographic and magnetic structure
      of barium-doped BiFeO3 compounds with approximate composition Bi(1-x)Ba(x)FeO(3
      x/2), as well as those of the fluorinated compounds Bi(1-x)Ba(x)FeO(3-x)F(x)
      (both with x = 0.2, 0.3), prepared by low-temperature fluorination of the oxide
      precursors using polyvinylidenedifluoride. Whereas the oxide compounds were
      obtained as cubic (x = 0.2) and slightly tetragonal (x = 0.3, c/a ~ 1.003)
      distorted perovskite compounds, a large tetragonal polar distortion was observed
      for the oxyfluoride compounds (c/a ~ 1.08 for x = 0.2 and ~1.05 for x = 0.3),
      being isostructural to tetragonal PbTiO3. Although described differently in
      previous reports on Ba-doped BiFeO3, the observed remanent magnetization is found
      to agree well with the amount of BaFe12O19 only detectable by neutron diffraction
      and the well-known magnetic properties of BaFe12O19. The oxyfluoride compounds
      show G-type antiferromagnetic ordering with magnetic moments lying in the a/b
      plane.

PMID- 25383953
TI  - Gestational heat stress alters postnatal offspring body composition indices and
      metabolic parameters in pigs.
AB  - The study objectives were to test the hypothesis that heat stress (HS) during
      gestational development alters postnatal growth, body composition, and biological
      response to HS conditions in pigs. To investigate this, 14 first parity crossbred
      gilts were exposed to one of four environmental treatments (TNTN, TNHS, HSTN, or
      HSHS) during gestation. TNTN and HSHS dams were exposed to thermal neutral (TN,
      cyclical 18-22 degrees C) or HS conditions (cyclical 28-34 degrees C) during the
      entire gestation, respectively. Dams assigned to HSTN and TNHS treatments were
      heat-stressed for the first or second half of gestation, respectively. Postnatal
      offspring were exposed to one of two thermal environments for an acute (24 h) or
      chronic (five weeks) duration in either constant TN (21 degrees C) or HS (35
      degrees C) environment. Exposure to chronic HS during their growth phase resulted
      in decreased longissimus dorsi cross-sectional area (LDA) in offspring from HSHS
      and HSTN treated dams whereas LDA was larger in offspring from dams in TNTN and
      TNHS conditions. Irrespective of HS during prepubertal postnatal growth, pigs
      from dams that experienced HS during the first half of gestation (HSHS and HSTN)
      had increased (13.9%) subcutaneous fat thickness compared to pigs from dams
      exposed to TN conditions during the first half of gestation. This metabolic
      repartitioning towards increased fat deposition in pigs from dams heat-stressed
      during the first half of gestation was accompanied by elevated blood insulin
      concentrations (33%; P = 0.01). Together, these results demonstrate HS during the
      first half of gestation altered metabolic and body composition parameters during
      future development and in biological responses to a subsequent HS challenge.

PMID- 25383957
TI  - Deficiency of interferon-gamma or its receptor promotes colorectal cancer
      development.
AB  - Genetic variations in interferon-gamma (IFN-gamma) and its receptor (IFNgammaR)
      subunits are closely associated with the risk of colorectal cancer (CRC) and
      survival after diagnosis. However, the role of loss of IFN-gamma or IFNgammaR
      function in the pathogenesis of CRC remains unclear. Here, we investigated the
      role of endogenous IFN-gamma deficiency in adenomatous polyposis coli (Apc)
      mediated intestinal tumor by developing a variant of Apc(Min/+) mice. The
      Apc(Min/+)IFN-gamma(+/-) mice presented with increased number and size of
      adenomas, and 41.7% of these mice developed adenocarcinoma. Molecular analyses of
      the adenomas suggested that heterozygous deletion of IFN-gamma promoted
      EGFR/Erk1/2 and Wnt/beta-catenin signaling. In vitro, IFN-gamma administration
      inhibited Apc-mutated HT-29 colon cancer cell proliferation and had no effect on
      the proliferation of HCT-116 colon cancer cells that express wild-type Apc.
      Besides, we challenged HT-29 cells with small interfering RNA targeting one of
      its receptor subunits IFNgammaR1. We found that knockdown of IFNgammaR1 in HT-29
      cells stimulated cell proliferation and colony formation, which was also related
      to the regulation of EGFR/Erk1/2 and Wnt/beta-catenin signaling. Thus, our
      results strongly support the notion that IFN-gamma and IFNgammaR1 act as a rate
      limiting factor in the development of CRC, uncovering a novel role for them in
      cancer biology. 

PMID- 25383958
TI  - Quantitative proteomic profiling of human articular cartilage degradation in
      osteoarthritis.
AB  - Osteoarthritis (OA) is the most common rheumatic pathology and is characterized
      primarily by articular cartilage degradation. Despite its high prevalence, there
      is no effective therapy to slow disease progression or regenerate the damaged
      tissue. Therefore, new diagnostic and monitoring tests for OA are urgently
      needed, which would also promote the development of alternative therapeutic
      strategies. In the present study, we have performed an iTRAQ-based quantitative
      proteomic analysis of secretomes from healthy human articular cartilage explants,
      comparing their protein profile to those from unwounded (early disease) and
      wounded (advanced disease) zones of osteoarthritic tissue. This strategy allowed
      us to identify a panel of 76 proteins that are distinctively released by the
      diseased tissue. Clustering analysis allowed the classification of proteins
      according to their different profile of release from cartilage. Among these
      proteins, the altered release of osteoprotegerin (decreased in OA) and periostin
      (increased in OA), both involved in bone remodelling processes, was verified in
      further analyses. Moreover, periostin was also increased in the synovial fluid of
      OA patients. Altogether, the present work provides a novel insight into the
      mechanisms of human cartilage degradation and a number of new cartilage
      characteristic proteins with possible biomarker value for early diagnosis and
      prognosis of OA. 

PMID- 25383959
TI  - Celastrol stimulates hypoxia-inducible factor-1 activity in tumor cells by
      initiating the ROS/Akt/p70S6K signaling pathway and enhancing hypoxia-inducible
      factor-1alpha protein synthesis.
AB  - Celastrol, a tripterine derived from the traditional Chinese medicine plant
      Tripterygium wilfordii Hook F. ("Thunder of God Vine"), has been reported to have
      multiple effects, such as anti-inflammation, suppression of tumor angiogenesis,
      inhibition of tumor growth, induction of apoptosis and protection of cells
      against human neurodegenerative diseases. However, the mechanisms that underlie
      these functions are not well defined. In this study, we reported for the first
      time that Celastrol could induce HIF-1alpha protein accumulation in multiple
      cancer cell lines in an oxygen-independent manner and that the enhanced HIF
      1alpha protein entered the nucleus and promoted the transcription of the HIF-1
      target genes VEGF and Glut-1. Celastrol did not influence HIF-1alpha
      transcription. Instead, Celastrol induced the accumulation of the HIF-1alpha
      protein by inducing ROS and activating Akt/p70S6K signaling to promote HIF-1alpha
      translation. In addition, we found that the activation of Akt by Celastrol was
      transient. With increased exposure time, inhibition of Hsp90 chaperone function
      by Celastrol led to the subsequent depletion of the Akt protein and thus to the
      suppression of Akt activity. Moreover, in HepG2 cells, the accumulation of HIF
      1alpha increased the expression of BNIP3, which induced autophagy. However, HIF
      1alpha and BNIP3 did not influence the cytotoxicity of Celastrol because the main
      mechanism by which Celastrol kills cancer cells is through stimulating ROS
      mediated JNK activation and inducing apoptosis. Furthermore, our data showed that
      the dose required for Celastrol to induce HIF-1alpha protein accumulation and
      enhance HIF-1alpha transcriptional activation was below its cytotoxic threshold.
      A cytotoxic dose of Celastrol for cancer cells did not display cytotoxicity in
      LO2 normal human liver cells, which indicated that the novel functions of
      Celastrol in regulating HIF-1 signaling and inducing autophagy might be used in
      new applications, such as in anti-inflammation and protection of cells against
      human neurodegenerative diseases. Future studies regarding these applications are
      required. 

PMID- 25383961
TI  - Clinical significance of adverse outcomes of placental abruption developing at
      home.
AB  - We reviewed the obstetric records of 40 singleton deliveries complicated by
      placental abruption which developed at patients' homes after 24 weeks' gestation.
      Of the 40 cases complicated by placental abruption which developed at home, 13
      cases (33%) were defined as showing adverse outcomes (5 cases of IUFD and 8 cases
      of UA pH < 7.0). The rate of patients who complained of abdominal pain without
      bleeding was higher in the adverse outcome group than in the control group (p =
      0.02). The average time interval between the onset and hospital (or clinic) visit
      in the adverse outcome group was longer than in the control group (p = 0.03).
      Adverse outcomes due to placental abruption which developed at home were
      associated with the symptom of pain without bleeding and a long time interval
      between the onset and hospital (or clinic) visit. 

PMID- 25383964
TI  - Dextransucrase-catalyzed elongation of polysaccharide brushes with immobilized
      mono-/di-saccharides as acceptors.
AB  - A quartz crystal microbalance (QCM) was used to monitor dextransucrase (DSase)
      catalyzed polysaccharide elongation on the glucose-/maltose-ended self-assembly
      monolayer (SAM) surfaces. Kinetic parameters of the enzymatic elongation indicate
      that maltose is a promising substrate acceptor for DSase. 

PMID- 25383963
TI  - Temporal variability of polybrominated diphenyl ether (PBDE) serum concentrations
      over one year.
AB  - Polybrominated diphenyl ethers (PBDEs) are flame retardant chemicals used in
      consumer products. They are common contaminants in human serum and associated
      with adverse health effects. Our objectives were to characterize PBDE serum
      concentrations in a New England cohort and assess temporal variability of this
      exposure biomarker over a one-year period. We collected three repeated
      measurements at six-month intervals from 52 office workers from the greater
      Boston (MA, United States) area from 2010 to 2011. The intraclass correlation
      coefficient for BDEs 28, 47, 99, 100, and 153 ranged from 0.87 to 0.99,
      indicating that a single serum measurement can reliably estimate exposure over a
      one-year period. This was true for both lipid adjusted and nonlipid adjusted
      concentrations. The kappa statistics, quantifying the level of agreement of
      categorical exposure classification, based on medians, tertiles, or quartiles
      ranged from 0.67 to 0.90. Some congeners showed nonsignificant increases from
      sampling round 1 (winter) to round 2 (summer) and significant decreases from
      round 2 to round 3 (winter). This study highlights the high reliability of a
      single serum PBDE measurement for use in human epidemiologic studies. 

PMID- 25383962
TI  - Examination of physiological function and biochemical disorders in a rat model of
      prolonged asphyxia-induced cardiac arrest followed by cardio pulmonary bypass
      resuscitation.
AB  - BACKGROUND: Cardiac arrest induces whole body ischemia, which causes damage to
      multiple organs particularly the heart and the brain. There is clinical and
      preclinical evidence that neurological injury is responsible for high mortality
      and morbidity of patients even after successful cardiopulmonary resuscitation. A
      better understanding of the metabolic alterations in the brain during ischemia
      will enable the development of better targeted resuscitation protocols that
      repair the ischemic damage and minimize the additional damage caused by
      reperfusion. METHOD: A validated whole body model of rodent arrest followed by
      resuscitation was utilized; animals were randomized into three groups: control,
      30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min
      cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were
      monitored during the procedures. An untargeted metabolic survey of heart and
      brain tissues following cardiac arrest and after CPB resuscitation was conducted
      to better define the alterations associated with each condition. RESULTS: After
      30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain
      function and weakened heart function in a physiological assessment. Heart and
      brain tissues harvested following 30 min ischemia had significant changes in the
      concentration of metabolites in lipid and carbohydrate metabolism. In addition,
      the brain had increased lysophospholipid content. CPB resuscitation significantly
      normalized metabolite concentrations in the heart tissue, but not in the brain
      tissue. CONCLUSION: The observation that metabolic alterations are seen primarily
      during cardiac arrest suggests that the events of ischemia are the major cause of
      neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired
      glycolysis and increased lysophospholipids observed only in the brain suggest
      that altered energy metabolism and phospholipid degradation may be a central
      mechanism in unresuscitatable brain damage.

PMID- 25383965
TI  - The relationship between the distribution of common carp and their environmental
      DNA in a small lake.
AB  - Although environmental DNA (eDNA) has been used to infer the presence of rare
      aquatic species, many facets of this technique remain unresolved. In particular,
      the relationship between eDNA and fish distribution is not known. We examined the
      relationship between the distribution of fish and their eDNA (detection rate and
      concentration) in a lake. A quantitative PCR (qPCR) assay for a region within the
      cytochrome b gene of the common carp (Cyprinus carpio or 'carp'), an ubiquitous
      invasive fish, was developed and used to measure eDNA in Lake Staring (MN, USA),
      in which both the density of carp and their distribution have been closely
      monitored for several years. Surface water, sub-surface water, and sediment were
      sampled from 22 locations in the lake, including areas frequently used by carp.
      In water, areas of high carp use had a higher rate of detection and concentration
      of eDNA, but there was no effect of fish use on sediment eDNA. The detection rate
      and concentration of eDNA in surface and sub-surface water were not significantly
      different (p>=0.5), indicating that eDNA did not accumulate in surface water. The
      detection rate followed the trend: high-use water > low-use water > sediment. The
      concentration of eDNA in sediment samples that were above the limit of detection
      were several orders of magnitude greater than water on a per mass basis, but a
      poor limit of detection led to low detection rates. The patchy distribution of
      eDNA in the water of our study lake suggests that the mechanisms that remove eDNA
      from the water column, such as decay and sedimentation, are rapid. Taken
      together, these results indicate that effective eDNA sampling methods should be
      informed by fish distribution, as eDNA concentration was shown to vary
      dramatically between samples taken less than 100 m apart. 

PMID- 25383966
TI  - A functional TNFAIP2 3'-UTR rs8126 genetic polymorphism contributes to risk of
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Accumulated evidences demonstrated that single nucleotide
      polymorphisms (SNPs) in mRNA 3'-untranslated region (3'-UTR) may impact microRNAs
      (miRNAs)-mediated expression regulation of oncogenes and tumor suppressors. There
      is a TNFAIP2 3'-UTR rs8126 T>C genetic variant which has been proved to be
      associated with head and neck cancer susceptibility. This SNP could disturb
      binding of miR-184 with TNFAIP2 mRNA and influence TNFAIP2 regulation. However,
      it is still unclear how this polymorphism is involved in development of
      esophageal squamous cell carcinoma (ESCC). Therefore, we hypothesized that the
      functional TNFAIP2 rs8126 SNP may affect TNFAIP2 expression and, thus, ESCC risk.
      METHODS: We investigated the association between the TNFAIP2 rs8126 variant and
      ESCC risk as well as the functional relevance on TNFAIP2 expression in vivo.
      Genotypes were determined in a case-control set consisted of 588 ESCC patients
      and 600 controls. The allele-specific regulation on TNFAIP2 expression by the
      rs8126 SNP was examined in normal and cancerous tissue specimens of esophagus.
      RESULTS: We found that individuals carrying the rs8126 CC or CT genotype had an
      OR of 1.89 (95%CI  = 1.23-2.85, P = 0.003) or 1.38 (95%CI  = 1.05-1.73, P =
      0.017) for developing ESCC in Chinese compared with individual carrying the TT
      genotype. Carriers of the rs8126 CC and CT genotypes had significantly lower
      TNFAIP2 mRNA levels than those with the TT genotypes in normal esophagus tissues
      (P<0.05). CONCLUSIONS: Our data demonstrate that functional TNFAIP2 rs8126
      genetic variant is a ESCC susceptibility SNP. These results support the
      hypothesis that genetic variants interrupting miRNA-mediated gene regulation
      might be important genetic modifiers of cancer risk.

PMID- 25383967
TI  - The influence of genetic drift and selection on quantitative traits in a plant
      pathogenic fungus.
AB  - Genetic drift and selection are ubiquitous evolutionary forces acting to shape
      genetic variation in populations. While their relative importance has been well
      studied in plants and animals, less is known about their relative importance in
      fungal pathogens. Because agro-ecosystems are more homogeneous environments than
      natural ecosystems, stabilizing selection may play a stronger role than genetic
      drift or diversifying selection in shaping genetic variation among populations of
      fungal pathogens in agro-ecosystems. We tested this hypothesis by conducting a
      QST/FST analysis using agricultural populations of the barley pathogen
      Rhynchosporium commune. Population divergence for eight quantitative traits (QST)
      was compared with divergence at eight neutral microsatellite loci (FST) for 126
      pathogen strains originating from nine globally distributed field populations to
      infer the effects of genetic drift and types of selection acting on each trait.
      Our analyses indicated that five of the eight traits had QST values significantly
      lower than FST, consistent with stabilizing selection, whereas one trait, growth
      under heat stress (22 degrees C), showed evidence of diversifying selection and
      local adaptation (QST>FST). Estimates of heritability were high for all traits
      (means ranging between 0.55-0.84), and average heritability across traits was
      negatively correlated with microsatellite gene diversity. Some trait pairs were
      genetically correlated and there was significant evidence for a trade-off between
      spore size and spore number, and between melanization and growth under benign
      temperature. Our findings indicate that many ecologically and agriculturally
      important traits are under stabilizing selection in R. commune and that high
      within-population genetic variation is maintained for these traits. 

PMID- 25383969
TI  - Systematic analysis of noncoding somatic mutations and gene expression
      alterations across 14 tumor types.
AB  - Somatic mutations in noncoding sequences are poorly explored in cancer, a rare
      exception being the recent identification of activating mutations in TERT
      regulatory DNA. Although this finding is suggestive of a general mechanism for
      oncogene activation, this hypothesis remains untested. Here we map somatic
      mutations in 505 tumor genomes across 14 cancer types and systematically screen
      for associations between mutations in regulatory regions and RNA-level changes.
      We identify recurrent promoter mutations in several genes but find that TERT
      mutations are exceptional in showing a strong and genome-wide significant
      association with increased expression. Detailed analysis of TERT across cancers
      shows that the strength of this association is highly variable and is strongest
      in copy number-stable cancers such as thyroid carcinoma. We additionally propose
      that TERT promoter mutations control expression of the nearby gene CLPTM1L. Our
      analysis provides a detailed pan-cancer view of TERT transcriptional activation
      but finds no clear evidence for frequent oncogenic promoter mutations beyond
      TERT. 

PMID- 25383970
TI  - Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term
      global distribution.
AB  - Enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea,
      produce heat-stable and/or heat-labile enterotoxins and at least 25 different
      colonization factors that target the intestinal mucosa. The genes encoding the
      enterotoxins and most of the colonization factors are located on plasmids found
      across diverse E. coli serogroups. Whole-genome sequencing of a representative
      collection of ETEC isolated between 1980 and 2011 identified globally distributed
      lineages characterized by distinct colonization factor and enterotoxin profiles.
      Contrary to current notions, these relatively recently emerged lineages might
      harbor chromosome and plasmid combinations that optimize fitness and
      transmissibility. These data have implications for understanding, tracking and
      possibly preventing ETEC disease. 

PMID- 25383968
TI  - Analysis of nascent RNA identifies a unified architecture of initiation regions
      at mammalian promoters and enhancers.
AB  - Despite the conventional distinction between them, promoters and enhancers share
      many features in mammals, including divergent transcription and similar modes of
      transcription factor binding. Here we examine the architecture of transcription
      initiation through comprehensive mapping of transcription start sites (TSSs) in
      human lymphoblastoid B cell (GM12878) and chronic myelogenous leukemic (K562)
      ENCODE Tier 1 cell lines. Using a nuclear run-on protocol called GRO-cap, which
      captures TSSs for both stable and unstable transcripts, we conduct detailed
      comparisons of thousands of promoters and enhancers in human cells. These
      analyses identify a common architecture of initiation, including tightly spaced
      (110 bp apart) divergent initiation, similar frequencies of core promoter
      sequence elements, highly positioned flanking nucleosomes and two modes of
      transcription factor binding. Post-initiation transcript stability provides a
      more fundamental distinction between promoters and enhancers than patterns of
      histone modification and association of transcription factors or co-activators.
      These results support a unified model of transcription initiation at promoters
      and enhancers. 

PMID- 25383973
TI  - Dendrimeric calcium-responsive MRI contrast agents with slow in vivo diffusion.
AB  - We report a methodology which enables the preparation of dendrimeric contrast
      agents sensitive to Ca(2+) when starting from the monomeric analogue. The Ca
      triggered longitudinal relaxivity response of these agents is not compromised by
      undertaking synthetic transformations, despite structural changes. The in vivo
      MRI studies in the rat cerebral cortex indicate that diffusion properties of
      dendrimeric contrast agents have great advantages as compared to their monomeric
      equivalents. 

PMID- 25383971
TI  - Variation at HLA-DRB1 is associated with resistance to enteric fever.
AB  - Enteric fever affects more than 25 million people annually and results from
      systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars
      A, B or C(1). We conducted a genome-wide association study of 432 individuals
      with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We
      observed strong association at rs7765379 (odds ratio (OR) for the minor allele =
      0.18, P = 4.5 * 10(-10)), a marker mapping to the HLA class II region, in
      proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric
      fever cases and 386 controls from Nepal and also in a second independent
      collection of 151 cases and 668 controls from Vietnam. Imputation-based fine
      mapping across the extended MHC region showed that the classical HLA-DRB1*04:05
      allele (OR = 0.14, P = 2.60 * 10(-11)) could entirely explain the association at
      rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against
      enteric fever, presumably through antigen presentation. 

PMID- 25383975
TI  - Relationship between pre-pregnancy maternal BMI with spontaneous preterm delivery
      and birth weight.
AB  - The aim of the present study was to find the relationship between pre-pregnancy
      maternal body mass index (BMI) with spontaneous preterm delivery and birth
      weight. A prospective cohort study was performed on 576 pregnant women. Maternal
      BMI was determined at the first prenatal visit between 8-12 weeks' gestation and
      considered as the pre-pregnancy maternal weight. The women were then monitored up
      to delivery. Out of 576 women, 396 completed the study. The demographics of the
      women in all BMI groups did not differ with regard to age, height, history of
      abortion and employment. A total of 21 women (5.3%) were underweight; 198 women
      (50%) were normal weight; 117 women (29.5%) were overweight and 60 (15.2%) were
      obese. There were no cases of morbidly obese (BMI > 40 kg/m(2)) women. Obesity in
      women had a positive correlation with higher gestational age at the time of
      delivery (r = 0.213, p = 0.015) and a heavier birth weight (r = 0.361, p =
      0.008). Low birth weight had a correlation with low maternal BMI (r = 0.157, p =
      0.041). Macrosomia was greater in obese women (p = 0.022) and BMI had a positive
      correlation with macrosomia (r = 0.224, p = 0.034). Preterm delivery showed a
      negative correlation with maternal BMI (r = -0.124, p = 0.004) and the women with
      a lower BMI had a greater number of preterm deliveries (p = 0.035). 

PMID- 25383974
TI  - Effect of oxygenated fuels on physicochemical and toxicological characteristics
      of diesel particulate emissions.
AB  - A systematic study was conducted to make a comparative evaluation of the effects
      of blending five different oxygenates (diglyme (DGM), palm oil methyl ester
      (PME), dimethyl carbonate (DMC), diethyl adipate (DEA), and butanol (Bu)) with
      ultralow sulfur diesel (ULSD) at 2% and 4% oxygen levels on physicochemical and
      toxicological characteristics of particulate emissions from a nonroad diesel
      engine. All blended fuels led to an overall decrease in the particulate mass
      concentration and elemental carbon (EC) emissions, which was strongly associated
      with the oxygen content in fuels and the specific type of fuels used. In general,
      the proportion of particulate-bound organic carbon (OC) and water-soluble organic
      carbon (WSOC) increased while using oxygenated fuel blends. Compared to ULSD, all
      fuel blends showed different emission factors of particle-phase PAHs and n
      alkanes, slight alterations in soot nanostructure, lower soot ignition
      temperature, and lower activation energy. The total counts of particles (<= 560
      nm diameter) emitted decreased gradually for ULSD blended with DMC, DEA, and Bu,
      while they increased significantly for other fuel blends. The in vitro toxicity
      of particulates significantly increased with ULSD blended with DMC and DEA, while
      it decreased when ULSD was blended with PME, DGM, and Bu.

PMID- 25383976
TI  - Modulation indices for volumetric modulated arc therapy.
AB  - The aim of this study is to present a modulation index (MI) for volumetric
      modulated arc therapy (VMAT) based on the speed and acceleration analysis of
      modulating-parameters such as multi-leaf collimator (MLC) movements, gantry
      rotation and dose-rate, comprehensively. The performance of the presented MI
      (MIt) was evaluated with correlation analyses to the pre-treatment quality
      assurance (QA) results, differences in modulating-parameters between VMAT plans
      versus dynamic log files, and differences in dose-volumetric parameters between
      VMAT plans versus reconstructed plans using dynamic log files. For comparison,
      the same correlation analyses were performed for the previously suggested
      modulation complexity score (MCS(v)), leaf travel modulation complexity score
      (LTMCS) and MI by Li and Xing (MI Li&Xing). In the two-tailed unpaired parameter
      condition, p values were acquired. The Spearman's rho (r(s)) values of MIt, MCSv,
      LTMCS and MI Li&Xing to the local gamma passing rate with 2%/2 mm criterion were 
      0.658 (p < 0.001), 0.186 (p = 0.251), 0.312 (p = 0.05) and -0.455 (p = 0.003),
      respectively. The values of rs to the modulating-parameter (MLC positions)
      differences were 0.917, -0.635, -0.857 and 0.795, respectively (p < 0.001). For
      dose-volumetric parameters, MIt showed higher statistically significant
      correlations than the conventional MIs. The MIt showed good performance for the
      evaluation of the modulation-degree of VMAT plans.

PMID- 25383972
TI  - Leveraging population admixture to characterize the heritability of complex
      traits.
AB  - Despite recent progress on estimating the heritability explained by genotyped
      SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense
      heritability (h(2)) remains. Explanations for this gap include rare variants or
      upward bias in family-based estimates of h(2) due to shared environment or
      epistasis. We estimate h(2) from unrelated individuals in admixed populations by
      first estimating the heritability explained by local ancestry (h(2)gamma). We
      show that h(2)gamma = 2FSTCtheta(1 - theta)h(2), where FSTC measures frequency
      differences between populations at causal loci and theta is the genome-wide
      ancestry proportion. Our approach is not susceptible to biases caused by
      epistasis or shared environment. We applied this approach to the analysis of 13
      phenotypes in 21,497 African-American individuals from 3 cohorts. For height and
      body mass index (BMI), we obtained h(2) estimates of 0.55 +/- 0.09 and 0.23 +/-
      0.06, respectively, which are larger than estimates of h(2)g in these and other
      data but smaller than family-based estimates of h(2). 

PMID- 25383977
TI  - Dynamic Observation on Opening of the Blood-Brain Barrier in the Primary Stage of
      Severely Scalded Rabbits, a Multimodal Study.
AB  - The aim of this study was to characterize the opening of the blood-brain barrier
      (BBB) in the primary stage of 50% total burn surface area in third degree scalded
      rabbits. Thirty healthy male New Zealand white rabbits were randomly assigned to
      1, 2, 3 and 4 hours post scald groups and an untreated control were used to
      establish a 50% total burn surface area third degree scalded model. I-labeled
      bovine serum albumin was used as a tracer to identify the earliest time point of
      BBB opening after a severe scald. Dual source CT and magnetic resonance imaging
      were used to visualize cerebral changes in vivo. Samples taken from the bilateral
      frontal, temporal, posterior cortex, cerebellum, brain stem, and basal ganglia
      were examined by light microscopy and transmission electron microscopy.
      Transmission electron microscopy observations confirmed that BBB had begun to
      open at 2 hours post scald. Intracellular edema of basal lamina and gliocytes,
      and the breakdown and an indistinct appearance of the tight junction of vascular
      endotheliocytes were observed at 3 hours post scald. A marked increase of I
      labeled bovine serum albumin intake was recorded at 3 hours post scald in all
      parts of the brain. Significantly reduced apparent diffusion coefficient values
      calculated from diffusion-weighted imaging were measured at 4 hours post scald
      within region of interests in all parts of the brain applied on apparent
      diffusion coefficient images. No significant alteration was seen in CT, diffusion
      weighted imaging, T1 or T2 weighted images. Opening of the BBB had begun at 2
      hours post scald; ie, before the occurrence of edema. The results of this study
      suggest that opening of the BBB might be a prerequisite for brain edema.

PMID- 25383978
TI  - Comparison of Decontamination Methods for Human Skin Grafts.
AB  - Skin grafts intended for autologous transplant may be dropped on the operating
      room floor during handling. The authors examined optimal procedures for
      decontaminating tissue intended for burn surgery. Porcine skin (5 * 5 cm
      sections) harvested from expired animals using standard procedures was inoculated
      with either 10(6) CFU/ml Staphylococcus aureus or Klebsiella pneumoniae.
      Decontaminating strategies were compared: 10% povidone iodine, 0.04%
      chlorhexidine, or 50 U/ml bacitracin for injection, and mechanical agitation
      using normal saline or sterile water; each agent was applied for 60 seconds. Each
      skin section was blended and plated on agar for bacterial enumeration using the
      spread plate method. Tissue viability was evaluated in parallel using a cell
      viability reagent, along with a control (heat at 200  degrees C for 5 min).
      Bacterial counts were log transformed; one-way ANOVA with Tukey-Kramer HSD
      analysis were performed. Concentration of organisms <10(5) CFU/g was considered
      clinically insignificant colonization. Eight donors provided 21 S. aureus and six
      K. pneumoniae samples. After exposure, mean organism concentration (CFU/g) was
      <10(5) for povidone iodine (S. aureus 2.83 * 10(4); K. pneumoniae 1.85 * 10(4)),
      chlorhexidine (S. aureus 4.52 * 10(4); K. pneumoniae 1.77 * 10(4)), and normal
      saline (K. pneumoniae 8.76 * 10(4)) treated groups. After log transform, only
      povidone iodine and chlorhexidine were found to be different from control in both
      groups. Viability was decreased in the positive control group, but not in
      treatment groups. Agents routinely used for surgical skin prep (povidone iodine
      and chlorhexidine), reduced both Gram-positive and Gram-negative contamination in
      tissue intended for skin grafting procedures. Antiseptic treatments did not
      impair the cellular viability of porcine skin.

PMID- 25383979
TI  - Frailty score on admission predicts outcomes in elderly burn injury.
AB  - With longer life expectancy, the number of burn injuries in the elderly continues
      to increase. Prediction of outcomes for the elderly is complicated by preinjury
      physical fitness and comorbid illness. The authors hypothesize that admission
      frailty assessment would be predictive of outcomes in the elderly burn
      population. Our primary aim was to determine if higher frailty scores were
      associated with higher risk of mortality for elderly burn patients. The secondary
      aims were to assess if higher frailty scores were associated with increased
      length of stay, increased needs for mechanical ventilation and poor discharge
      disposition. A 2-year retrospective chart review was performed of all admitted
      acute burn patients 65 years or older. Data collected included: age, gender,
      %TBSA of burn injury, presence of inhalation injury, in hospital mortality,
      hospital length of stay, ventilator days, ICU length of stay, surgical
      procedures, insurance status, and discharge disposition. Frailty scores were
      assessed from admission data and calculated using the Canadian Study of Health
      and Aging clinical frailty scale. A total of 89 patients met entry criteria. Mean
      age was 75.3 +/- 8.1 years and consisted of 62 men and 27 women. Mean %TBSA was
      9.6 +/- 9.1% and mean frailty score (FS) was 4.5 +/- 1.2. Eighty patients
      survived to discharge and nine died. Nonsurvivors had significantly higher FS
      compared to survivors (5.2 +/- 1.2 vs 4.4 +/- 1.2). FS were also significantly
      higher in patients discharged to skilled nursing facilities (SNF) (5.34 +/- 0.9)
      compared to those who were discharged home (4.1 +/- 1.2) or to physical
      rehabilitation facilities (4 +/- 1.5). Multivariate linear regression analysis
      revealed that age (B = 0.04) and discharge to SNF (B = 1.2) are independently
      associated with higher FS. However, survivors were independently associated with
      a significantly lower FS (B = -1.3). Multivariate logistic regression analysis
      revealed high admission FS independently increased the risk of discharge to SNF
      (odds ratio of 2.5 [1.3-4.8, 95% confidence interval]) and increased the risk of
      mortality (odds ratio of 1.67 [1.01-2.7, 95% confidence interval]). Frailty
      scores on admission allow for a more complete assessment of elderly patients and
      can be used to establish benchmark models for burn injury outcomes. In addition
      FS can be used as a research tool to improve outcomes for elderly burn injured
      patients.

PMID- 25383980
TI  - A noninvasive computational method for fluid resuscitation monitoring in
      pediatric burns: a preliminary report.
AB  - The fluid resuscitation needs of children with small area burns are difficult to
      predict. The authors hypothesized that a novel computational algorithm called the
      compensatory reserve index (CRI), calculated from the photoplethysmogram
      waveform, would correlate with percent total body surface area (%TBSA) and fluid
      administration in children presenting with <=20% TBSA burns. The authors recorded
      photoplethysmogram waveforms from burn-injured children that were later processed
      by the CRI algorithm. A CRI of 1 represents supine normovolemia; a CRI of 0
      represents the point at which a subject is predicted to experience hemodynamic
      decompensation. CRI values from the first 10 minutes of monitoring were compared
      to clinical data. Waveform data were available for 27 children with small to
      moderate sized burns (4-20 %TBSA). The average age was 6.3 +/- 1.1 years, the
      average %TBSA was 10.4 +/- 0.8%, and the average CRI was 0.36 +/- 0.03. CRI
      inversely correlated with the %TBSA (P < .001). Twenty children were transferred
      with an average reported %TBSA of 16.5 +/- 1.4%, which was significantly higher
      than the actual %TBSA (P < .001). CRI correlated better with actual %TBSA
      compared to reported %TBSA (P = .02). CRI correlated with the amount of fluid
      resuscitation given at the time of CRI measurement (P = .02) and was inversely
      related to total fluids given per 24 hours for children with adequate urine
      output (>0.5 ml/kg/hr) (P < .001). The CRI is decreased in children with small to
      moderate size burns, and correlates with %TBSA and fluid administration. This
      suggests that the CRI may be useful for fluid resuscitation guidance, warranting
      further study.

PMID- 25383982
TI  - Patterns of use of oral anticancer treatments in France: a Retrospective Analysis
      of Cancer Treatments given ORally from 2004 to 2012 (Re-ACTOR study).
AB  - BACKGROUNDS AND OBJECTIVES: Increasing use of oral anticancer treatments (OATs)
      in oncology is modifying the treatment paradigm for cancer. Nonetheless,
      available data on the pattern of use of OATs and its evolution over time are
      limited. The objective of this study was to describe the patterns of use of OATs
      in France from 2004 to 2012. METHODS: A retrospective analysis was performed
      using Oncology Analyzer, a physician survey database. All patients actively
      treated by an oral or an intravenous anticancer treatment between October 2004
      and September 2012 were enrolled in the database. Descriptive analyses were
      performed by treatment category with a focus on the last year of collection and
      the evolution across the study period. RESULTS: From October 2011 to September
      2012, a sample of 7426 patients treated by oral or intravenous active anticancer
      treatments was analyzed: 74% of patients receiving an OAT were diagnosed with a
      solid tumor, 52% of whom had a stage IV cancer. The use of OATs increased with
      age and was the highest in patients over 80 years. From 2004 to 2012, the
      proportion of cancer patients receiving OATs increased by four percentage points
      (from 28.4% to 32.5%). Additionally, for treatments available in both forms, a
      marked preference for oral formulations was observed. LIMITATIONS: The patterns
      and trend of use prior to 2004 were not addressed due to lack of information in
      the database. The use of a market research database is relevant for highly
      prevalent cancers but for rare cancers the sample size is limited, underlining
      the utility of using other data sources such as cancer registries. CONCLUSIONS:
      The Re-ACTOR study provides an overview of OAT use in France, which was
      prescribed to 32% of cancer patients in France in 2012, principally to older
      patients and to those with solid tumors and with metastatic disease.

PMID- 25383983
TI  - Heavier alkaline earth catalyzed ene-yne cyclizations: atom-efficient access to
      tetrahydroisoquinoline frameworks.
AB  - Tetrahydroisoquinoline frameworks may be accessed with 100% atom efficiency
      through the alkaline earth catalyzed addition of primary amines to ene-yne
      substrates through a sequence of intermolecular alkene and intramolecular alkyne
      hydroamination steps. 

PMID- 25383981
TI  - Association of brain-derived neurotrophic factor gene Val66Met polymorphism with
      primary dysmenorrhea.
AB  - Primary dysmenorrhea (PDM), the most prevalent menstrual cycle-related problem in
      women of reproductive age, is associated with negative moods. Whether the
      menstrual pain and negative moods have a genetic basis remains unknown. Brain
      derived neurotrophic factor (BDNF) plays a key role in the production of central
      sensitization and contributes to chronic pain conditions. BDNF has also been
      implicated in stress-related mood disorders. We screened and genotyped the BDNF
      Val66Met polymorphism (rs6265) in 99 Taiwanese (Asian) PDMs (20-30 years old) and
      101 age-matched healthy female controls. We found that there was a significantly
      higher frequency of the Met allele of the BDNF Val66Met polymorphism in the PDM
      group. Furthermore, BDNF Met/Met homozygosity had a significantly stronger
      association with PDM compared with Val carrier status. Subsequent
      behavioral/hormonal assessments of sub-groups (PDMs = 78, controls = 81; eligible
      for longitudinal multimodal neuroimaging battery studies) revealed that the BDNF
      Met/Met homozygous PDMs exhibited a higher menstrual pain score (sensory
      dimension) and a more anxious mood than the Val carrier PDMs during the menstrual
      phase. Although preliminary, our study suggests that the BDNF Val66Met
      polymorphism is associated with PDM in Taiwanese (Asian) people, and BDNF Met/Met
      homozygosity may be associated with an increased risk of PDM. Our data also
      suggest the BDNF Val66Met polymorphism as a possible regulator of menstrual pain
      and pain-related emotions in PDM. Absence of thermal hypersensitivity may connote
      an ethnic attribution. The presentation of our findings calls for further genetic
      and neuroscientific investigations of PDM.

PMID- 25383984
TI  - (-) Arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone
      receptor beta.
AB  - Lignans are important biologically active dietary polyphenolic compounds.
      Consumption of foods that are rich in lignans is associated with positive health
      effects. Using modeling tools to probe the ligand-binding pockets of molecular
      receptors, we found that lignans have high docking affinity for the human thyroid
      hormone receptor beta. Follow-up experimental results show that lignans (-)
      arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone
      receptor beta. The modeled complexes show key plausible interactions between the
      two ligands and important amino acid residues of the receptor. 

PMID- 25383985
TI  - [A descriptive study of malocclusion in Malian, Cuban and Venezuelan 5-9 year-old
      children].
AB  - INTRODUCTION: Awareness of the oral health status of a population is
      indispensable to correctly plan, organize, direct and supervise dental care. Its
      periodic evaluation allows monitoring the progress of primary dental care
      programs, and introducing necessary adjustments in order to accomplish dental
      care goals. In this context, early orthodontic intervention allows correct
      development of oral occlusion and prevents complications. OBJECTIVE: The purpose
      of this study is to study dental occlusion characteristics in Malian, Cuban, and
      Venezuelan children from Bamako, Mali (between 2006 and 2008), the state of
      Portuguesa, Venezuela (between 2011 and 2013), and Bartolome Maso in Granma, Cuba
      (between 2009 and 2011). It also aims to determine prevalence, to classify
      malocclusion according to Angle criteria, and to identify risk factors for this
      condition. METHODS: A descriptive cross-sectional study was conducted using
      simple or stratified random sampling depending on the patient?s age, the time
      period of the mission (two years) and the place where the study was conducted.
      Among the patients seeking basic dental care, those who were between five and
      nine years old were included and their data collected in a form designed for that
      purpose. RESULTS: Malocclusion is most frequently found in Cuban children
      (79.1%), followed by Venezuelan children (67.2%) and Malian children (40%). Angle
      type I malocclusion predominates with 50.2% in Malian, 58.5% in Venezuelan, and
      78.7 in Cubans. One of the most important risk factors was dental cavities in the
      three groups: 91.8% in Malian, 78.26% in Venezuelan, and 34.7% in Cubans.
      Deforming oral habits were also observed from 40.7%, 65.5% up to 72.1%. Premature
      tooth loss appeared between 60% and 84.1% and was directly related to dental
      cavities. Interproximal cavities and defective dental restorations were also
      observed. CONCLUSION: Malocclusion was found in over 40% of cases and Angle type
      I was the most prevalent. Risk factors were the same for all groups, and they
      were dental cavities, deforming oral habits, premature tooth loss, and
      interproximal cavities. Muscular dysfunctions were present, but they were not
      associated to malocclusion.

PMID- 25383986
TI  - Vibrational spectroscopy: recent developments to revolutionize forensic science.

PMID- 25383987
TI  - Distribution and growth of Vibrio parahaemolyticus in southern Chilean clams
      (Venus antiqua) and blue mussels (Mytilus chilensis).
AB  - We evaluated the distribution and growth of Vibrio parahaemolyticus in the inland
      sea of southern Chile, where the world's largest foodborne gastroenteritis
      outbreak by the pandemic strain O3:K6 occurred in 2005. Intertidal samples of
      Mytilus chilensis and Venus antiqua were collected around port towns between 41
      degrees 28'S and 43 degrees 07'S, during April to May 2011 and January to March
      2012. We used most probable number real-time polymerase chain reaction (MPN-PCR)
      for enumeration of the tlh, tdh, and trh genes in freshly harvested bivalves and
      after a controlled postharvest temperature abuse. Pathogenic markers (tdh+ or
      trh+) were not detected. Total V. parahaemolyticus (tlh+) in freshly harvested
      samples reached up to 0.38 and 3.66 log MPN/g in 2011 and 2012, respectively,
      with values close to or above 3 log MPN/g only near Puerto Montt (41 degrees
      28'S, 72 degrees 55'W). Enrichments by temperature abuse (>2 log MPN/g) occurred
      mainly in the same zone, regardless of the year, suggesting that both natural or
      anthropogenic exposure to high temperatures were more critical. Lower salinity
      and higher sea surface temperature in Reloncavi Sound and Reloncavi Estuary were
      consistent with our observations and allowed confirmation of the existence of a
      high-risk zone near Puerto Montt. Based on the results, a strategy focused on
      risk management inside this defined hazard zone is recommended.

PMID- 25383988
TI  - Rotaxane formation by cucurbit[7]uril in water and DMSO solutions.
AB  - The cucurbit[7]uril (CB7) host forms rotaxane-type complexes with dumbbell
      shaped, cationic guests bis(3,5-dimethoxybenzyl)-4,4'-bipyridinium (1(2+)) and
      bis(3,5-diethoxybenzyl)-4,4'-bipyridinium (2(2+)). The kinetics of complex
      formation is slower with the latter guest because of its bulkier end groups.
      Rotaxane formation was found to be thermodynamically more favorable and
      kinetically faster in D2O than in DMSO-d6 solution, which highlights the
      importance of hydrophobic interactions in the assembly of cucurbituril complexes.

PMID- 25383989
TI  - Science from evaluation: testing hypotheses about differential effects of three
      youth-focused suicide prevention trainings.
AB  - As part of an evaluation component of a youth suicide prevention, a quasi
      experimental repeated measures design tested hypotheses about two brief suicide
      prevention gatekeeper trainings (Question, Persuade, Refer [QPR] and RESPONSE)
      and one longer suicide intervention skills training (Applied Suicide Intervention
      Skills Training [ASIST]). All three trainings showed large changes in prevention
      attitudes and self-efficacy, largely maintained at follow-up. ASIST trainees had
      large increases in asking at-risk youth about suicide at follow-up. Convergent
      with other research, modeling and role-play in training are crucial to increased
      prevention behaviors. Practice and research implications are discussed, including
      social work roles in suicide prevention and research. 

PMID- 25383990
TI  - Highly viscous antibody solutions are a consequence of network formation caused
      by domain-domain electrostatic complementarities: insights from coarse-grained
      simulations.
AB  - Therapeutic monoclonal antibody (mAb) candidates that form highly viscous
      solutions at concentrations above 100 mg/mL can lead to challenges in
      bioprocessing, formulation development, and subcutaneous drug delivery. Earlier
      studies of mAbs with concentration-dependent high viscosity have indicated that
      mAbs with negatively charged Fv regions have a dipole-like quality that increases
      the likelihood of reversible self-association. This suggests that weak
      electrostatic intermolecular interactions can form transient antibody networks
      that participate in resistance to solution deformation under shear stress. Here
      this hypothesis is explored by parametrizing a coarse-grained (CG) model of an
      antibody using the domain charges from four different mAbs that have had their
      concentration-dependent viscosity behaviors previously determined. Multicopy
      molecular dynamics simulations were performed for these four CG mAbs at several
      concentrations to understand the effect of surface charge on mass diffusivity,
      pairwise interactions, and electrostatic network formation. Diffusion
      coefficients computed from simulations were in qualitative agreement with
      experimentally determined viscosities for all four mAbs. Contact analysis
      revealed an overall greater number of pairwise interactions for the two mAbs in
      this study with high concentration viscosity issues. Further, using equilibrated
      solution trajectories, the two mAbs with high concentration viscosity issues
      quantitatively formed more features of an electrostatic network than the other
      mAbs. The change in the number of these network features as a function of
      concentration is related to the number of pairwise interactions formed by
      electrostatic complementarities between antibody domains. Thus, transient
      antibody network formation caused by domain-domain electrostatic
      complementarities is the most probable origin of high concentration viscosity for
      mAbs in this study. 

PMID- 25383992
TI  - Addressing disparities in mental health agencies: strategies to implement the
      National CLAS Standards in Mental Health.
AB  - Historically, the mental health system has not effectively addressed the needs of
      culturally and linguistically diverse individuals (President's New Freedom
      Commission on Mental Health, 2003), which has contributed to significant racial
      and ethnic disparities in mental health care (USDHHS, 2001). This paper focuses
      on exploring how a U.S. Department of Health and Human Services' Office of
      Minority Health policy initiative, the National Standards for Culturally and
      Linguistically Appropriate Services (CLAS) in Health and Health Care (or the
      National CLAS Standards), may be used by mental health agencies to reduce mental
      health care disparities. The National CLAS Standards are a set of action steps
      that inform and facilitate the implementation of culturally and linguistically
      appropriate services. We first discuss the role of cultural and linguistic
      competency in mental health care disparities reduction efforts, and then describe
      specific strategies to facilitate the organizational implementation of the
      National CLAS Standards.

PMID- 25383991
TI  - Toward culturally centered integrative care for addressing mental health
      disparities among ethnic minorities.
AB  - Despite decades of research, recognition and treatment of mental illness and its
      comorbidities still remain a significant public health problem in the United
      States. Ethnic minorities are identified as a population that is vulnerable to
      mental health disparities and face unique challenges pertaining to mental health
      care. Psychiatric illness is associated with great physical, emotional,
      functional, and societal burden. The primary health care setting may be a
      promising venue for screening, assessment, and treatment of mental illnesses for
      ethnic minority populations. We propose a comprehensive, innovative, culturally
      centered integrated care model to address the complexities within the health care
      system, from the individual level, which includes provider and patient factors,
      to the system level, which includes practice culture and system functionality
      issues. Our multidisciplinary investigative team acknowledges the importance of
      providing culturally tailored integrative health care to holistically concentrate
      on physical, mental, emotional, and behavioral problems among ethnic minorities
      in a primary care setting. It is our intention that the proposed model will be
      useful for health practitioners, contribute to the reduction of mental health
      disparities, and promote better mental health and well-being for ethnic minority
      individuals, families, and communities.

PMID- 25383994
TI  - Building the gateway to success: an appraisal of progress in reaching underserved
      families and reducing racial disparities in school-based mental health.
AB  - School-based mental health (SBMH) services hold the promise of reducing barriers
      to care among underserved children and families in need, which can in turn reduce
      racial disparities in care. Yet, questions remain about the potential of SBMH for
      equitably reaching diverse communities. In particular, reaching Asian American
      youth in SBMH may remain a challenge even compared with other immigrant and
      ethnic minority groups, such as Latinos. This article describes the development
      and evaluates the service capacity of a SBMH platform in a medium-sized public
      school district serving predominantly low-income Latino and Asian American
      families. Service capacity was built through the creation and coordination of a
      system of community partnerships. Analyses of needs assessment and service
      referral and utilization patterns revealed no significant racial/ethnic
      differences in overall rates of mental health need between Latino and Asian
      American students; yet, Asian Americans were underrepresented in referrals to
      SBMH. However, once referred to care, there was no difference in the likelihood
      that Asian American and Latino students received treatment. Although there was an
      increase in capacity to link students to care, work remains to improve processes
      of identification to reduce unmet need across diverse groups.

PMID- 25383993
TI  - Translating disparities research to policy: a qualitative study of state mental
      health policymakers' perceptions of mental health care disparities report cards.
AB  - Report cards have been used to increase accountability and quality of care in
      health care settings, and to improve state infrastructure for providing quality
      mental health care services. However, to date, report cards have not been used to
      compare states on racial/ethnic disparities in mental health care. This
      qualitative study examines reactions of mental health care policymakers to a
      proposed mental health care disparities report card generated from population
      based survey data of mental health and mental health care utilization. We
      elicited feedback about the content, format, and salience of the report card.
      Interviews were conducted with 9 senior advisors to state policymakers and 1
      policy director of a national nongovernmental organization from across the United
      States. Four primary themes emerged: fairness in state-by-state comparisons;
      disconnect between the goals and language of policymakers and researchers;
      concerns about data quality; and targeted suggestions from policymakers.
      Participant responses provide important information that can contribute to making
      evidence-based research more accessible to policymakers. Further, policymakers
      suggested ways to improve the structure and presentation of report cards to make
      them more accessible to policymakers, and to foster equity considerations during
      the implementation of new health care legislation. To reduce mental health care
      disparities, effort is required to facilitate understanding between researchers
      and relevant stakeholders about research methods, standards for interpretation of
      research-based evidence, and its use in evaluating policies aimed at ameliorating
      disparities.

PMID- 25383996
TI  - A critical review of culturally sensitive treatments for depression:
      recommendations for intervention and research.
AB  - Recent meta-analyses and reviews have showed that culturally adapted mental
      health interventions are more effective for racial and ethnic minorities than
      traditional unadapted psychotherapy. Despite the advances in providing culturally
      sensitive mental health services, disparities among racial and ethnic minorities
      still exist. As a body of literature on culturally sensitive treatments
      accumulates, there is a need to examine what makes a treatment for specific
      presenting problems culturally sensitive. This article presents a critical review
      of existing culturally sensitive treatments for depression because it is one of
      the most common and debilitating mental disorders. In particular, we examined
      what treatment modalities were used, what types of adaptations were implemented,
      and what populations were targeted. The conceptual framework this review uses to
      categorize existing culturally sensitive treatments includes a top-down, a bottom
      up, or an integrative approach. The review reveals that the majority of
      culturally sensitive treatments for depression employed an evidence-based bottom
      up approach, which involved general and practical adaptations, such as
      translating materials or infusing specific cultural values. Most studies used
      cognitive-behavioral strategies and included Latinos and African Americans.
      Recommendations and future directions in interventions and research are discussed
      to decrease mental health care disparities among ethnic minorities.

PMID- 25383995
TI  - Working together to solve disparities: Latina/o parents' contributions to the
      adaptation of a preventive intervention for childhood conduct problems.
AB  - Left untreated, conduct problems can have significant and long-lasting negative
      effects on children's development. Despite the existence of many effective
      interventions, U.S. Latina/o children are less likely to access or receive
      evidence-based services. Seeking to build the foundation to address these service
      disparities, the current study used a Community-Based Participatory Research
      approach to examine U.S. Latina/o parents' perceptions of the need for
      interventions to prevent childhood disruptive behaviors in their community in
      general, and of an existing evidence-based intervention-parent-child interaction
      therapy (PCIT)-in particular. Results suggest that parents recognize a need for
      prevention resources in their community and value most of the core features of
      PCIT. Nevertheless, important directions for potential adaptation and expansion
      of PCIT into a prevention approach were identified. Results point to several
      goals for future study with the potential to ameliorate the unmet mental health
      needs experienced by U.S. Latina/o families with young children at risk for
      developing conduct problems.

PMID- 25383997
TI  - Factors associated with mental health service use in urban, impoverished, trauma
      exposed adults.
AB  - This study utilized the Expanded Behavioral Model of Health Service Use Among
      Vulnerable Populations to investigate disparities in mental health care use among
      a community sample of urban, impoverished, trauma-exposed adults. Self-report
      questionnaires were completed by 135 adults with a lifetime history of traumatic
      stress exposure. Results suggested approximately 20% of the sample were receiving
      mental health services, and these individuals were primarily getting services at
      outpatient mental health facilities. Social support, positive attitudes toward
      treatment seeking, and occupational disability were significantly associated with
      current mental health service use. Logistic regression analyses indicated that
      after controlling for significant covariates, occupational disability was the
      only need variable that predicted current mental health service utilization (OR =
      1.25, 95% CI = 1.08 to 1.45, p < .01). Improving attitudes toward treatment
      seeking as well as identifying occupational difficulties may be important avenues
      for improving willingness to seek care and decreasing disparities in care for
      trauma-exposed adults. Implications for mental health policy and practice are
      discussed.

PMID- 25383998
TI  - Toward the early recognition of psychosis among Spanish-speaking adults on both
      sides of the U.S.-Mexico border.
AB  - Lack of knowledge about psychosis, a condition oftentimes associated with serious
      mental illness, may contribute to disparities in mental health service use.
      Psychoeducational interventions aimed at improving psychosis literacy have
      attracted significant attention recently, but few have focused on the growing
      numbers of ethnic and linguistic minorities in countries with large immigrant
      populations, such as the United States. This paper reports on 2 studies designed
      to evaluate the effectiveness of a DVD version of La CLAve, a psychoeducational
      program that aims to increase psychosis literacy among Spanish-speaking Latinos.
      Study 1 is a randomized control study to test directly the efficacy of a DVD
      version of La CLAve for Spanish speakers across a range of educational
      backgrounds. Fifty-seven medical students and 68 community residents from Mexico
      were randomly assigned to view either La CLAve or a psychoeducational program of
      similar length regarding caregiving. Study 2 employed a single-subjects design to
      evaluate the effectiveness of the DVD presentation when administered by a
      community mental health educator. Ninety-three Spanish-speakers from San Diego,
      California completed assessments both before and after receiving the DVD
      training. Results from these 2 studies indicate that the DVD version of La CLAve
      is capable of producing a range of psychosis literacy gains for Spanish-speakers
      in both the United States and Mexico, even when administered by a community
      worker. Thus, it has potential for widespread dissemination and use among
      underserved communities of Spanish-speaking Latinos and for minimizing
      disparities in mental health service use, particularly as it relates to
      insufficient knowledge of psychosis.

PMID- 25383999
TI  - Mental health screening among newly arrived refugees seeking routine obstetric
      and gynecologic care.
AB  - Posttraumatic stress disorder (PTSD), anxiety, and depression are common mental
      health disorders in the refugee population. High rates of violence, trauma, and
      PTSD among refugee women remain unaddressed. The process of implementing a mental
      health screening tool among multiethnic, newly arrived refugee women receiving
      routine obstetric and gynecologic care in a dedicated refugee women's health
      clinic is described. The Refugee Health Screener-15 (RHS-15) is a culturally
      responsive, efficient, validated screening instrument that detects symptoms of
      emotional distress across diverse refugee populations and languages. An
      interdisciplinary community partnership was established with a local behavioral
      health services agency to facilitate the referral of women scoring positive on
      the RHS-15. Staff and provider training sessions, as well as the incorporation of
      bicultural, multilingual cultural health navigators, greatly facilitated
      linguistically appropriate care coordination for refugee women in a culturally
      sensitive manner. Twenty-six (23.2%) of the 112 women who completed the RHS-15
      scored positive, of which 14 (53.8%) were Iraqi, 1 (3.8%) was Burmese, and 3
      (11.5%) were Somali. Among these 26 women, 8 (30.8%) are actively receiving
      mental health services and 5 (19.2%) have appointments scheduled. However, 13
      (50%) are not enrolled in mental health care because of either declining services
      (46.2%) or a lack of insurance (53.8%). Screening for mental disorders among
      refugee women will promote greater awareness and identify those individuals who
      would benefit from further mental health evaluation and treatment. Sustainable
      interdisciplinary models of care are necessary to promote health education,
      dispel myths, and reduce the stigma of mental health.

PMID- 25384000
TI  - An innovative community-oriented approach to prevention and early intervention
      with refugees in the United States.
AB  - Thousands of refugees from around the world resettle in the United States every
      year. Many refugees suffer from mental health disorders as a result of
      experiences living in or escaping from their turbulent homelands, and many also
      experience mental health issues as they settle in their new host countries. As
      such, it is important to intervene during the early stages of refugee
      resettlement to help prevent or mitigate mental illness symptoms. However,
      because of several access and utilization barriers, such as stigma, refugees are
      not apt to receive needed mental health services. Moreover, the traditional
      Western model of treatment can be culturally incongruent with refugee practices.
      Alternative, culturally sensitive, community-based approaches must be considered.
      This article presents a community-oriented prevention and early intervention
      model that can be used with newly arrived refugees with limited English
      proficiency. Goals of the model are to increase knowledge of mental health and
      mental health service options to refugees, as well as support the process of
      adjusting to life in the United States. The New Refugee Services Project,
      developed by the Center for Survivors of Torture department of Asian Americans
      for Community Involvement (AACI) in San Santa Clara County, California is
      presented as an example case study. The structure outlined in this article aims
      to support the development, implementation, and assessment of future preventative
      interventions for refugee populations.

PMID- 25384001
TI  - Applying behavior change theory to technology promoting veteran mental health
      care seeking.
AB  - Despite the availability of effective mental health interventions, the vast
      majority of veterans with a mental disorder underutilize psychological services.
      Contemporary research has revealed that several factors such as low education,
      stigma, stoicism, lack of knowledge, and negative beliefs about mental health
      services are associated with veterans' underutilization of services. In this
      article, the authors provide an overview of factors that affect symptomatic
      veterans' decisions about whether to seek mental health services. Second, they
      describe the theory of planned behavior (Ajzen & Fishbein, 1980), a useful model
      for understanding mental health care seeking that can inform the development of
      technology-based interventions designed to increase veterans' willingness to seek
      psychological services. Third, the authors describe the development of
      Considering Professional Help, a personalized web-based tool developed by the
      Department of Veterans Affairs, which has been designed to promote mental health
      care seeking in veterans with mental health problems.

PMID- 25384002
TI  - Increased ligament thickness in previously sprained ankles as measured by
      musculoskeletal ultrasound.
AB  - CONTEXT: Lateral ankle sprains are among the most common injuries in sport, with
      the anterior talofibular ligament (ATFL) most susceptible to damage. Although we
      understand that after a sprain, scar tissue forms within the ligament, little is
      known about the morphologic changes in a ligament after injury. OBJECTIVE: To
      examine whether morphologic differences exist in the thickness of the ATFL in
      healthy, coper, and unstable-ankle groups. DESIGN: Cross-sectional study.
      SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 80 National
      Collegiate Athletic Association Division I collegiate athletes (43 women, 37 men,
      age = 18.2 +/- 1.1 years, height = 175.8 +/- 11.1 cm, body mass = 75.0 +/- 16.9
      kg) participated in this study. They were categorized into the healthy, coper, or
      unstable group by history of ankle sprains and score on the Cumberland Ankle
      Instability Tool. MAIN OUTCOME MEASURE(S): A musculoskeletal sonographic image of
      the ATFL was obtained from each ankle. Thickness of the ATFL was measured at the
      midpoint of the ligament between the attachments on the lateral malleolus and
      talus. RESULTS: A group-by-limb interaction was evident (P = .038). The ATFLs of
      the injured limb for the coper group (2.20 +/- 0.47 mm) and the injured limb for
      the unstable group (2.28 +/- 0.53 mm) were thicker than the ATFL of the "injured"
      limb of the healthy group (1.95 +/- 0.29 mm) at P = .015 and P = .015,
      respectively. No differences were seen in the uninjured limbs among groups.
      CONCLUSIONS: Because ATFL thicknesses of the healthy group's uninjured ankles
      were similar, we contend that lasting morphologic changes occurred in those with
      a previous injury to the ankle. Similar differences were seen between the injured
      limbs of the coper and unstable groups, so there must be another explanation for
      the sensations of instability and the reinjuries in the unstable group.

PMID- 25384003
TI  - Incidence and descriptive epidemiology of injuries to college ultimate players.
AB  - CONTEXT: The burden of injuries to college ultimate players has never been fully
      described. OBJECTIVE: To quantify the injury rate in ultimate players and
      describe the diagnoses, anatomic locations, and mechanisms of injuries. DESIGN:
      Descriptive epidemiology study. SETTING: College ultimate teams in the United
      States during the 2012 season. MAIN OUTCOME MEASURE(S): Initial injury rate per
      1000 athlete-exposures. RESULTS: The initial injury rate in college ultimate
      players was 12.64 per 1000 athlete-exposures; the rate did not differ between men
      and women (P = .5). Bivariate analysis indicated that injuries occurred twice as
      often during games as during practices, men were more likely than women to be
      injured when laying out for the disc, and men were more likely to incur strains
      and sprains than women. CONCLUSIONS: Injury patterns to college ultimate players
      were similar to those for athletes in other National Collegiate Athletic
      Association sports. This is the first study to systematically describe injuries
      to ultimate players.

PMID- 25384004
TI  - Distributional analyses in the picture-word interference paradigm: Exploring the
      semantic interference and the distractor frequency effects.
AB  - The present study explores the distributional features of two important effects
      within the picture-word interference paradigm: the semantic interference and the
      distractor frequency effects. These two effects display different and specific
      distributional profiles. Semantic interference appears greatly reduced in faster
      response times, while it reaches its full magnitude only in slower responses.
      This can be interpreted as a sign of fluctuant attentional efficiency in
      resolving response conflict. In contrast, the distractor frequency effect is
      mediated mainly by a distributional shift, with low-frequency distractors
      uniformly shifting reaction time distribution towards a slower range of
      latencies. This finding fits with the idea that distractor frequency exerts its
      effect by modulating the point in time in which operations required to discard
      the distractor can start. Taken together, these results are congruent with
      current theoretical accounts of both the semantic interference and distractor
      frequency effects. Critically, distributional analyses highlight and further
      describe the different cognitive dynamics underlying these two effects,
      suggesting that this analytical tool is able to offer important insights about
      lexical access during speech production. 

PMID- 25384005
TI  - Service-oriented node scheduling scheme for wireless sensor networks using Markov
      random field model.
AB  - Future wireless sensor networks are expected to provide various sensing services
      and energy efficiency is one of the most important criterions. The node
      scheduling strategy aims to increase network lifetime by selecting a set of
      sensor nodes to provide the required sensing services in a periodic manner. In
      this paper, we are concerned with the service-oriented node scheduling problem to
      provide multiple sensing services while maximizing the network lifetime. We
      firstly introduce how to model the data correlation for different services by
      using Markov Random Field (MRF) model. Secondly, we formulate the service
      oriented node scheduling issue into three different problems, namely, the multi
      service data denoising problem which aims at minimizing the noise level of sensed
      data, the representative node selection problem concerning with selecting a
      number of active nodes while determining the services they provide, and the multi
      service node scheduling problem which aims at maximizing the network lifetime.
      Thirdly, we propose a Multi-service Data Denoising (MDD) algorithm, a novel multi
      service Representative node Selection and service Determination (RSD) algorithm,
      and a novel MRF-based Multi-service Node Scheduling (MMNS) scheme to solve the
      above three problems respectively. Finally, extensive experiments demonstrate
      that the proposed scheme efficiently extends the network lifetime. 

PMID- 25384006
TI  - Portable solid phase micro-extraction coupled with ion mobility spectrometry
      system for on-site analysis of chemical warfare agents and simulants in water
      samples.
AB  - On-site analysis is an efficient approach to facilitate analysis at the location
      of the system under investigation as it can result in more accurate, more precise
      and quickly available analytical data. In our work, a novel self-made thermal
      desorption based interface was fabricated to couple solid-phase microextraction
      with ion mobility spectrometry for on-site water analysis. The portable interface
      can be connected with the front-end of an ion mobility spectrometer directly
      without other modifications. The analytical performance was evaluated via the
      extraction of chemical warfare agents and simulants in water samples. Several
      parameters including ionic strength and extraction time have been investigated in
      detail. The application of the developed method afforded satisfactory recoveries
      ranging from 72.9% to 114.4% when applied to the analysis of real water samples. 

PMID- 25384007
TI  - Measuring snow liquid water content with low-cost GPS receivers.
AB  - The amount of liquid water in snow characterizes the wetness of a snowpack. Its
      temporal evolution plays an important role for wet-snow avalanche prediction, as
      well as the onset of meltwater release and water availability estimations within
      a river basin. However, it is still a challenge and a not yet satisfyingly solved
      issue to measure the liquid water content (LWC) in snow with conventional in situ
      and remote sensing techniques. We propose a new approach based on the attenuation
      of microwave radiation in the L-band emitted by the satellites of the Global
      Positioning System (GPS). For this purpose, we performed a continuous low-cost
      GPS measurement experiment at the Weissfluhjoch test site in Switzerland, during
      the snow melt period in 2013. As a measure of signal strength, we analyzed the
      carrier-to-noise power density ratio (C/N0) and developed a procedure to
      normalize these data. The bulk volumetric LWC was determined based on assumptions
      for attenuation, reflection and refraction of radiation in wet snow. The onset of
      melt, as well as daily melt-freeze cycles were clearly detected. The temporal
      evolution of the LWC was closely related to the meteorological and snow
      hydrological data. Due to its non-destructive setup, its cost-efficiency and
      global availability, this approach has the potential to be implemented in
      distributed sensor networks for avalanche prediction or basin-wide melt onset
      measurements. 

PMID- 25384008
TI  - Localisation of an unknown number of land mines using a network of vapour
      detectors.
AB  - We consider the problem of localising an unknown number of land mines using
      concentration information provided by a wireless sensor network. A number of
      vapour sensors/detectors, deployed in the region of interest, are able to detect
      the concentration of the explosive vapours, emanating from buried land mines. The
      collected data is communicated to a fusion centre. Using a model for the
      transport of the explosive chemicals in the air, we determine the unknown number
      of sources using a Principal Component Analysis (PCA)-based technique. We also
      formulate the inverse problem of determining the positions and emission rates of
      the land mines using concentration measurements provided by the wireless sensor
      network. We present a solution for this problem based on a probabilistic Bayesian
      technique using a Markov chain Monte Carlo sampling scheme, and we compare it to
      the least squares optimisation approach. Experiments conducted on simulated data
      show the effectiveness of the proposed approach.

PMID- 25384009
TI  - A provably-secure ECC-based authentication scheme for wireless sensor networks.
AB  - A smart-card-based user authentication scheme for wireless sensor networks (in
      short, a SUA-WSN scheme) is designed to restrict access to the sensor data only
      to users who are in possession of both a smart card and the corresponding
      password. While a significant number of SUA-WSN schemes have been suggested in
      recent years, their intended security properties lack formal definitions and
      proofs in a widely-accepted model. One consequence is that SUA-WSN schemes
      insecure against various attacks have proliferated. In this paper, we devise a
      security model for the analysis of SUA-WSN schemes by extending the widely
      accepted model of Bellare, Pointcheval and Rogaway (2000). Our model provides
      formal definitions of authenticated key exchange and user anonymity while
      capturing side-channel attacks, as well as other common attacks. We also propose
      a new SUA-WSN scheme based on elliptic curve cryptography (ECC), and prove its
      security properties in our extended model. To the best of our knowledge, our
      proposed scheme is the first SUA-WSN scheme that provably achieves both
      authenticated key exchange and user anonymity. Our scheme is also computationally
      competitive with other ECC-based (non-provably secure) schemes. 

PMID- 25384010
TI  - Odometry for ground moving agents by optic flow recorded with optical mouse
      chips.
AB  - Optical mouse chips-equipped with adequate lenses-can serve as small, light,
      precise, fast, and cheap motion sensors monitoring optic flow induced by self
      motion of an agent in a contrasted environment. We present a device that extracts
      self motion parameters exclusively from flow in eight mouse sensors. Four pairs
      of sensors with opposite azimuth are mounted on a sensor head, each individual
      sensor looking down with -45 degrees  elevation. The head is mounted on a
      carriage and is moved at constant height above a textured planar ground. The
      calibration procedure and tests on the precision of self motion estimates are
      reported.

PMID- 25384011
TI  - Liquid-Liquid Phase Transitions in Tetrahedrally Coordinated Fluids via Wertheim
      Theory.
AB  - Network interpenetration has been proposed as a mechanism for generating liquid
      liquid phase transitions in one component systems. We introduce a model of four
      coordinated particles, which explicitly treats the system as a mixture of two
      interacting interpenetrating networks that can freely exchange particles. This
      model can be solved within Wertheim's theory for associating fluids and shows
      liquid-liquid phase separations (in addition to the gas-liquid) for a wide range
      of model parameters. We find that originating a liquid-liquid transition requires
      a small degree of interpenetrability and a preference for intranetwork bonding.
      Physically, these requirements can be seen as controlling the softness of the
      particle-particle interaction and the bond flexibility, in full agreement with
      recent findings [Smallenburg, F.; Filion, L.; Sciortino, F. Nat. Phys. 2014, 10,
      653]. 

PMID- 25384012
TI  - Common FXIII and fibrinogen polymorphisms in abdominal aortic aneurysms.
AB  - INTRODUCTION: Abdominal aortic aneurysms (AAA) are characterized by a progressive
      dilatation of the abdominal aorta, and are associated with a high risk of rupture
      once the dilatation exceeds 55 mm in diameter. A large proportion of AAA develops
      an intraluminal thrombus, which contributes to hypoxia, inflammation and tissue
      degradation. We have previously shown that patients with AAA produce clots with
      altered structure which is more resistant to fibrinolysis. The aim of this study
      was to investigate genetic polymorphisms of FXIII and fibrinogen in AAA to
      identify how changes to these proteins may play a role in the development of AAA.
      METHODS: Subjects of Western/European descent, >=55 years of age (520 AAA
      patients and 449 controls) were genotyped for five polymorphisms (FXIII-A
      Val34Leu, FXIII-B His95Arg, FXIII-B Splice Variant (intron K nt29576C-G), Fib-A
      Thr312Ala and Fib-B Arg448Lys) by RT-PCR. Data were analysed by chi2 test and
      CubeX. RESULTS: The FXIII-B Arg95 allele associated with AAA (Relative risk -
      1.240, CI 1.093-1.407, P = 0.006). There was no association between FXIII-A
      Val34Leu, FXIII-B Splice Variant, Fib-A Thr312Ala or Fib-B Arg448Lys and AAA.
      FXIII-B His95Arg and FXIII-B Splice variant (intron K nt29576C-G) were in
      negative linkage disequilibrium (D' = -0.609, p = 0.011). DISCUSSION: The FXIII-B
      Arg95 variant is associated with an increased risk of AAA. These data suggest a
      possible role for FXIII in AAA pathogenesis.

PMID- 25384013
TI  - Differences in life-histories refute ecological equivalence of cryptic species
      and provide clues to the origin of bathyal Halomonhystera (Nematoda).
AB  - The discovery of morphologically very similar but genetically distinct species
      complicates a proper understanding of the link between biodiversity and ecosystem
      functioning. Cryptic species have been frequently observed to co-occur and are
      thus expected to be ecological equivalent. The marine nematode Halomonhystera
      disjuncta contains five cryptic species (GD1-5) that co-occur in the
      Westerschelde estuary. In this study, we investigated the effect of three abiotic
      factors (salinity, temperature and sulphide) on life-history traits of three
      cryptic H. disjuncta species (GD1-3). Our results show that temperature had the
      most profound influence on all life-cycle parameters compared to a smaller effect
      of salinity. Life-history traits of closely related cryptic species were
      differentially affected by temperature, salinity and presence of sulphides which
      shows that cryptic H. disjuncta species are not ecologically equivalent. Our
      results further revealed that GD1 had the highest tolerance to a combination of
      sulphides, high salinities and low temperatures. The close phylogenetic position
      of GD1 to Halomonhystera hermesi, the dominant species in sulphidic sediments of
      the Hakon Mosby mud volcano (Barent Sea, 1280 m depth), indicates that both
      species share a recent common ancestor. Differential life-history responses to
      environmental changes among cryptic species may have crucial consequences for our
      perception on ecosystem functioning and coexistence of cryptic species. 

PMID- 25384014
TI  - Tissue quality assessment using a novel direct elasticity assessment device (the
      E-finger): a cadaveric study of prostatectomy dissection.
AB  - INTRODUCTION: Minimally invasive radical prostatectomy (RP) (robotic and
      laparoscopic), have brought improvements in the outcomes of RP due to improved
      views and increased degrees of freedom of surgical devices. Robotic and
      laparoscopic surgeries do not incorporate haptic feedback, which may result in
      complications secondary to inadequate tissue dissection (causing positive
      surgical margins, rhabdosphincter damage, etc). We developed a micro-engineered
      device (6 mm2 sized) [E-finger]) capable of quantitative elasticity assessment,
      with amplitude ratio, mean ratio and phase lag representing this. The aim was to
      assess the utility of the device in differentiating peri-prostatic tissue types
      in order to guide prostate dissection. MATERIAL AND METHODS: Two embalmed and 2
      fresh frozen cadavers were used in the study. Baseline elasticity values were
      assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed
      cadavers using the micro-engineered device. A measurement grid was created to
      span from the bladder, across the prostate and onto the rhabdosphincter of fresh
      frozen cadavers to enable a systematic quantitative elasticity assessment of the
      entire area by 2 independent assessors. Tissue was sectioned along each row of
      elasticity measurement points, and stained with haematoxylin and eosin (H&E).
      Image analysis was performed with Image Pro Premier to determine the histology at
      each measurement point. RESULTS: Statistically significant differences in
      elasticity were identified between bladder, prostate and sphincter in both
      embalmed and fresh frozen cadavers (p = < 0.001). Intra-class correlation (ICC)
      reliability tests showed good reliability (average ICC = 0.851). Sensitivity and
      specificity for tissue identification was 77% and 70% respectively to a
      resolution of 6 mm2. CONCLUSIONS: This cadaveric study has evaluated the ability
      of our elasticity assessment device to differentiate bladder, prostate and
      rhabdosphincter to a resolution of 6 mm2. The results provide useful data for
      which to continue to examine the use of elasticity assessment devices for tissue
      quality assessment with the aim of giving haptic feedback to surgeons performing
      complex surgery.

PMID- 25384015
TI  - Preoperative measurement of serum thyroglobulin to predict malignancy in thyroid
      nodules: a systematic review.
AB  - Several articles have assessed the role of preoperative serum thyroglobulin (Tg)
      as predictor of malignancy of thyroid nodules, with particular focus on nodules
      with indeterminate cytology. However, the role of serum Tg as diagnostic marker
      remains unclear. The aim of the study was to perform a systematic review to add
      more evidence-based data on this topic. A comprehensive literature search was
      conducted to find relevant published articles on this topic. MeSH terms were:
      "thyroglobulin" and "predict*". In order to include only recent serum Tg assay
      methods, we analyzed the timeframe between 2001 and July 31(st), 2014. To expand
      our search, references of the retrieved articles were also screened. Thirteen
      studies, including 3,580 patients, were analyzed. Nine out of these studies
      reported data on thyroid nodules with prior indeterminate cytology. Preoperative
      serum Tg levels demonstrated suboptimal accuracy in discriminating malignant from
      benign nodules due to a significant overlap of values between these groups.
      However, most articles demonstrated a statistically significant difference in
      mean or median serum Tg between patients with cancer and benign lesions
      correlated to final histology. Furthermore, most studies reported Tg as
      independent predictor of malignancy. According to the most recent literature, the
      preoperative measurement of Tg alone fails to discriminate thyroid cancers from
      benign lesions. However, our data show that Tg is an independent predictor of
      malignancy; as a consequence, the presurgical determination of Tg should be
      considered in patients with thyroid nodules, especially when cytology is
      indeterminate.

PMID- 25384016
TI  - Erythrocytic mobilization enhanced by the granulocyte colony-stimulating factor
      is associated with reduced anthrax-lethal-toxin-induced mortality in mice.
AB  - Anthrax lethal toxin (LT), one of the primary virulence factors of Bacillus
      anthracis, causes anthrax-like symptoms and death in animals. Experiments have
      indicated that levels of erythrocytopenia and hypoxic stress are associated with
      disease severity after administering LT. In this study, the granulocyte colony
      stimulating factor (G-CSF) was used as a therapeutic agent to ameliorate anthrax
      LT- and spore-induced mortality in C57BL/6J mice. We demonstrated that G-CSF
      promoted the mobilization of mature erythrocytes to peripheral blood, resulting
      in a significantly faster recovery from erythrocytopenia. In addition, combined
      treatment using G-CSF and erythropoietin tended to ameliorate B. anthracis-spore
      elicited mortality in mice. Although specific treatments against LT-mediated
      pathogenesis remain elusive, these results may be useful in developing feasible
      strategies to treat anthrax. 

PMID- 25384018
TI  - Near-ultraviolet-sensitive graphene/porous silicon photodetectors.
AB  - Porous silicon (PSi) is recognized as an attractive building block for photonic
      devices because of its novel properties including high ratio of surface to volume
      and high light absorption. We first report near-ultraviolet (UV)-sensitive
      graphene/PSi photodetectors (PDs) fabricated by utilizing graphene and PSi as a
      carrier collector and a photoexcitation layer, respectively. Thanks to high light
      absorption and enlarged energy-band gap of PSi, the responsivity (Ri) and quantum
      efficiency (QE) of the PDs are markedly enhanced in the near-UV range. The
      performances of PDs are systemically studied for various porosities of PSi,
      controlled by varying the electroless-deposition time (td) of Ag nanoparticles
      for the use of Si etching. Largest gain is obtained at td = 3 s, consistent with
      the maximal enhancement of Ri and QE in the near UV range, which originates from
      the well-defined interface at the graphene/PSi junction, as proved by atomic- and
      electrostatic-force microscopies. Optimized response speed is ~10 times faster
      compared to graphene/single-crystalline Si PDs. These and other unique PD
      characteristics prove to be governed by typical Schottky diode-like transport of
      charge carriers at the graphene/PSi junctions, based on bias-dependent variations
      of the band profiles, resulting in novel dark- and photocurrent behaviors.

PMID- 25384017
TI  - Clinical effectiveness of integrating depression care management into medicare
      home health: the Depression CAREPATH Randomized trial.
AB  - IMPORTANCE: Among older home health care patients, depression is highly
      prevalent, is often inadequately treated, and contributes to hospitalization and
      other poor outcomes. Feasible and effective interventions are needed to reduce
      this burden of depression. OBJECTIVE: To determine whether, among older Medicare
      Home Health recipients who screen positive for depression, patients of nurses
      receiving randomization to an intervention have greater improvement in depressive
      symptoms during 1 year than patients receiving enhanced usual care. DESIGN,
      SETTING, AND PARTICIPANTS: This cluster randomized effectiveness trial conducted
      at 6 home health care agencies nationwide assigned nurse teams to an intervention
      (12 teams) or to enhanced usual care (9 teams). Between January 13, 2009, and
      December 6, 2012, Medicare Home Health patients 65 years and older who screened
      positive for depression on routine nursing assessments were recruited, underwent
      assessment, and were followed up at 3, 6, and 12 months by research staff blinded
      to intervention status. Patients were interviewed at home and by telephone. Of
      502 eligible patients, 306 enrolled in the study. INTERVENTIONS: The Depression
      Care for Patients at Home (Depression CAREPATH) trial requires nurses to manage
      depression at routine home visits by weekly symptom assessment, medication
      management, care coordination, education, and goal setting. Nurses' training
      totaled 7 hours (4 onsite and 3 via the web). Researchers telephoned intervention
      team supervisors every other week. MAIN OUTCOMES AND MEASURES: Depression
      severity, assessed by the 24-item Hamilton Scale for Depression (HAM-D). RESULTS:
      The 306 participants were predominantly female (69.6%), were racially/ethnically
      diverse (18.0% black and 16.0% Hispanic), and had a mean (SD) age of 76.5 (8.0)
      years. In the full sample, the intervention had no effect (P = .13 for
      intervention * time interaction). Adjusted HAM-D scores (Depression CAREPATH vs
      control) did not differ at 3 months (10.5 vs 11.4, P = .26) or at 6 months (9.3
      vs 10.5, P = .12) but reached significance at 12 months (8.7 vs 10.6, P = .05).
      In the subsample with mild depression (HAM-D score, <10), the intervention had no
      effect (P = .90), and HAM-D scores did not differ at any follow-up points. Among
      208 participants with a HAM-D score of 10 or higher, the Depression CAREPATH
      demonstrated effectiveness (P = .02), with lower HAM-D scores at 3 months (14.1
      vs 16.1, P = .04), at 6 months (12.0 vs 14.7, P = .02), and at 12 months (11.8 vs
      15.7, P = .005). CONCLUSION AND RELEVANCE: Home health care nurses can
      effectively integrate depression care management into routine practice. However,
      the clinical benefit seems to be limited to patients with moderate to severe
      depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01979302.

PMID- 25384019
TI  - SPIDIA-RNA: second external quality assessment for the pre-analytical phase of
      blood samples used for RNA based analyses.
AB  - One purpose of the EC funded project, SPIDIA, is to develop evidence-based
      quality guidelines for the pre-analytical handling of blood samples for RNA
      molecular testing. To this end, two pan-European External Quality Assessments
      (EQAs) were implemented. Here we report the results of the second SPIDIA-RNA EQA.
      This second study included modifications in the protocol related to the blood
      collection process, the shipping conditions and pre-analytical specimen handling
      for participants. Participating laboratories received two identical proficiency
      blood specimens collected in tubes with or without an RNA stabilizer. For pre
      defined specimen storage times and temperatures, laboratories were asked to
      perform RNA extraction from whole blood according to their usual procedure and to
      return extracted RNA to the SPIDIA facility for further analysis. These RNA
      samples were evaluated for purity, yield, integrity, stability, presence of
      interfering substances, and gene expression levels for the validated markers of
      RNA stability: FOS, IL1B, IL8, GAPDH, FOSB and TNFRSF10c. Analysis of the gene
      expression results of FOS, IL8, FOSB, and TNFRSF10c, however, indicated that the
      levels of these transcripts were significantly affected by blood collection tube
      type and storage temperature. These results demonstrated that only blood
      collection tubes containing a cellular RNA stabilizer allowed reliable gene
      expression analysis within 48 h from blood collection for all the genes
      investigated. The results of these two EQAs have been proposed for use in the
      development of a Technical Specification by the European Committee for
      Standardization. 

PMID- 25384020
TI  - Magnetization transfer prepared gradient echo MRI for CEST imaging.
AB  - Chemical exchange saturation transfer (CEST) is an emerging MRI contrast
      mechanism that is capable of noninvasively imaging dilute CEST agents and local
      properties such as pH and temperature, augmenting the routine MRI methods.
      However, the routine CEST MRI includes a long RF saturation pulse followed by
      fast image readout, which is associated with high specific absorption rate and
      limited spatial resolution. In addition, echo planar imaging (EPI)-based fast
      image readout is prone to image distortion, particularly severe at high field. To
      address these limitations, we evaluated magnetization transfer (MT) prepared
      gradient echo (GRE) MRI for CEST imaging. We proved the feasibility using
      numerical simulations and experiments in vitro and in vivo. Then we optimized the
      sequence by serially evaluating the effects of the number of saturation steps, MT
      saturation power (B1), GRE readout flip angle (FA), and repetition time (TR) upon
      the CEST MRI, and further demonstrated the endogenous amide proton CEST imaging
      in rats brains (n = 5) that underwent permanent middle cerebral artery occlusion.
      The CEST images can identify ischemic lesions in the first 3 hours after
      occlusion. In summary, our study demonstrated that the readily available MT
      prepared GRE MRI, if optimized, is CEST-sensitive and remains promising for
      translational CEST imaging.

PMID- 25384021
TI  - Identifying genetic variants for heart rate variability in the acetylcholine
      pathway.
AB  - Heart rate variability is an important risk factor for cardiovascular disease and
      all-cause mortality. The acetylcholine pathway plays a key role in explaining
      heart rate variability in humans. We assessed whether 443 genotyped and imputed
      common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4,
      CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with
      variation in an established measure of heart rate variability reflecting
      parasympathetic control of the heart rhythm, the root mean square of successive
      differences (RMSSD) of normal RR intervals. The association was studied in a two
      stage design in individuals of European descent. First, analyses were performed
      in a discovery sample of four cohorts (n = 3429, discovery stage). Second,
      findings were replicated in three independent cohorts (n = 3311, replication
      stage), and finally the two stages were combined in a meta-analysis (n = 6740).
      RMSSD data were obtained under resting conditions. After correction for multiple
      testing, none of the SNPs showed an association with RMSSD. In conclusion, no
      common genetic variants for heart rate variability were identified in the largest
      and most comprehensive candidate gene study on the acetylcholine pathway to date.
      Future gene finding efforts for RMSSD may want to focus on hypothesis free
      approaches such as the genome-wide association study.

PMID- 25384022
TI  - Patients with encapsulating peritoneal sclerosis have increased peritoneal
      expression of connective tissue growth factor (CCN2), transforming growth factor
      beta1, and vascular endothelial growth factor.
AB  - INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a devastating
      complication of peritoneal dialysis (PD). The pathogenesis is not exactly known
      and no preventive strategy or targeted medical therapy is available. CCN2 has
      both pro-fibrotic and pro-angiogenic actions and appears an attractive target.
      Therefore, we studied peritoneal expression of CCN2, as well as TGFbeta1 and
      VEGF, in different stages of peritoneal fibrosis. MATERIALS AND METHODS: Sixteen
      PD patients were investigated and compared to 12 hemodialysis patients and four
      pre-emptively transplanted patients. Furthermore, expression was investigated in
      12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS.
      Peritoneal tissue was taken during kidney transplantation procedure or during EPS
      surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and
      plasma were determined. Samples were examined by qPCR, histology,
      immunohistochemistry, and ELISA. RESULTS: Peritoneal CCN2 expression was 5-fold
      higher in PD patients compared to pre-emptively transplanted patients (P < 0.05),
      but did not differ from hemodialysis patients. Peritoneal expression of TGFbeta1
      and VEGF were not different between the three groups; neither was peritoneal
      thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35
      fold, P < 0.001), TGFbeta1 (24-fold, P < 0.05), and VEGF (77-fold, P < 0.001)
      compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly
      localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels
      were significantly higher in peritoneal effluent of EPS patients compared to
      levels in dialysate of PD patients (12.0 +/- 4.5 vs. 0.91 +/- 0.92 ng/ml, P <
      0.01), while plasma CCN2 levels were not increased. CONCLUSIONS: Peritoneal
      expression of CCN2, TGFbeta1, and VEGF are significantly increased in EPS
      patients. In early stages of peritoneal fibrosis, only CCN2 expression is
      slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally
      driven response. The potential of CCN2 as biomarker and target for CCN2
      inhibiting agents to prevent or treat EPS warrants further study.

PMID- 25384024
TI  - Severe cognitive impairment associated with intrathecal antibodies to the NR1
      subunit of the N-methyl-D-aspartate receptor in a patient with multiple
      sclerosis.
AB  - IMPORTANCE: Some patients with multiple sclerosis (MS) can either present with or
      develop severe cognitive impairment during the course of their disease. However,
      the mechanisms underlying severe cognitive dysfunction in MS are not well
      understood. OBSERVATIONS: We report on a woman who was diagnosed as having MS at
      age 33 years and who after giving birth at age 37 years developed cognitive
      impairment with severe memory dysfunction as the leading symptom. Treatment with
      different immunotherapies, including cyclophosphamide and natalizumab, did not
      improve her cognitive deficits, necessitating admission to a nursing home at age
      39 years. During a thorough reevaluation at age 43 years, analysis of current and
      stored cerebrospinal fluid and serum samples demonstrated an intrathecal
      synthesis of IgG antibodies to the NR1 subunit of the N-methyl-D-aspartate
      receptor, that is, the characteristic laboratory finding of anti-N-methyl-D
      aspartate receptor encephalitis. Although the patient initially stabilized under
      therapy with corticosteroids, plasma exchange, and mitoxantrone, severe cognitive
      impairment persisted and she eventually died from the sequelae of her disease.
      CONCLUSIONS AND RELEVANCE: This report suggests that the occasional occurrence of
      severe cognitive impairment in patients with MS may, in some cases, be related to
      a superimposed antibody-mediated autoimmune encephalitis.

PMID- 25384023
TI  - Effects of in vitro supplementation with Syzygium cumini (L.) on platelets from
      subjects affected by diabetes mellitus.
AB  - The aim of this study was to assess the in vitro effects of Syzygium cumini (L.)
      (Sc) incubation on platelets from patients with diabetes, in order to test its
      efficacy as a potential adjuvant therapy. This study was performed on 77 patients
      with diabetes [29 in good (DMgc) and 48 in poor glycemic control (DMpc)] and 85
      controls. In patients, platelets were analyzed at recruitment and after in vitro
      Sc incubation (final concentration of 200 ug/ml for 3 hours at 37  degrees C),
      whereas in controls only basal evaluation was performed. Lipoperoxide and nitric
      oxide (NO) levels, superoxide dismutase (SOD) and Na(+)/K(+) ATPase activities,
      total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of
      fluorescent probes 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH)
      and 1-6-phenyl-1,3,5-hexatriene (DPH) were determined. Collagen-induced platelet
      aggregation was also evaluated. In vitro Sc activity counteracts oxidative
      damage, by improving platelet function through augmented membrane fluidity and
      Na(+)/K(+) ATPase activity; it also enhances antioxidant system functionality by
      increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels
      both in whole samples and in DMgc and DMpc. In addition, a slight tendency
      towards collagen-induced platelet aggregation decrease after Sc was observed.
      However, all these parameters, even after improvement, did not reach the levels
      of control subjects. Our results suggest that Sc may have a preventive and
      protective effect in oxidative damage progression associated with diabetes
      mellitus and its complications. If our data will be confirmed, Sc supplementation
      might become a further tool in the management of this disease, especially in view
      of its easy availability, safety, low cost, and absence of side effects.

PMID- 25384026
TI  - Preparation of core-shell coordination molecular assemblies via the enrichment of
      structure-directing "codes" of bridging ligands and metathesis of metal units.
AB  - A series of molybdenum- and copper-based MOPs were synthesized through
      coordination-driven process of a bridging ligand (3,3'-PDBAD, L(1)) and dimetal
      paddlewheel clusters. Three conformers of the ligand exist with an ideal bridging
      angle between the two carboxylate groups of 0 degrees  (H2alpha-L(1)), 120
      degrees  (H2beta-L(1)), and of 90 degrees  (H2gamma-L(1)), respectively. At
      ambient or lower temperature, H2L(1) and Mo2(OAc)4 or Cu2(OAc)4 were crystallized
      into a molecular square with gamma-L(1) and Mo2/Cu2 units. With proper
      temperature elevation, not only the molecular square with gamma-L(1) but also a
      lantern-shaped cage with alpha-L(1) formed simultaneously. Similar to how Watson
      Crick pairs stabilize the helical structure of duplex DNA, the core-shell
      molecular assembly possesses favorable H-bonding interaction sites. This is
      dictated by the ligand conformation in the shell, coding for the formation and
      providing stabilization of the central lantern shaped core, which was not
      observed without this complementary interaction. On the basis of the
      crystallographic implications, a heterobimetallic cage was obtained through a
      postsynthetic metal ion metathesis, showing different reactivity of coordination
      bonds in the core and shell. As an innovative synthetic strategy, the site
      selective metathesis broadens the structural diversity and properties of
      coordination assemblies. 

PMID- 25384025
TI  - Fusarochromanone induces G1 cell cycle arrest and apoptosis in COS7 and HEK293
      cells.
AB  - Fusarochromanone (FC101), a mycotoxin produced by the fungus Fusarium equiseti,
      is frequently observed in the contaminated grains and feedstuffs, which is toxic
      to animals and humans. However, the underlying molecular mechanism remains to be
      defined. In this study, we found that FC101 inhibited cell proliferation and
      induced cell death in COS7 and HEK293 cells in a concentration-dependent manner.
      Flow cytometric analysis showed that FC101 induced G1 cell cycle arrest and
      apoptosis in the cells. Concurrently, FC101 downregulated protein expression of
      cyclin D1, cyclin-dependent kinases (CDK4 and CDK6), and Cdc25A, and upregulated
      expression of the CDK inhibitors (p21Cip1 and p27Kip1), resulting in
      hypophosphorylation of Rb. FC101 also inhibited protein expression of Bcl-2, Bcl
      xL, Mcl-1 and survivin, and induced expression of BAD, leading to activation of
      caspase 3 and cleavage of PARP, indicating caspase-dependent apoptosis. However,
      Z-VAD-FMK, a pan-caspase inhibitor, only partially prevented FC101-induced cell
      death, implying that FC101 may induce cell death through both caspase-dependent
      and -independent mechanisms. Our results support the notion that FC101 executes
      its toxicity at least by inhibiting cell proliferation and inducing cell death. 

PMID- 25384027
TI  - Prediction of glycated hemoglobin levels at 3 months after metabolic surgery
      based on the 7-day plasma metabolic profile.
AB  - Metabolic surgery has been shown to provide better glycemic control for type 2
      diabetes than conventional therapies. Still, the outcomes of the surgery are
      variable, and prognostic markers reflecting the metabolic changes by the surgery
      are yet to be established. NMR-based plasma metabolomics followed by multivariate
      regression was used to test the correlation between the metabolomic profile at 7
      days after surgery and glycated hemoglobin (HbA1c) levels at 3-months (and up to
      12 months with less patients), and to identify the relevant markers. Metabolomic
      profiles at 7-days could differentiate the patients according to the HbA1c
      improvement status at 3-months. The HbA1c values were predicted based on the
      metabolomics profile with partial least square regression, and found to be
      correlated with the observed values. Metabolite analysis suggested that 3
      Hydroxybutyrate (3-HB) and glucose contributes to this prediction, and the [3
      HB]/[glucose] exhibited a modest to good correlation with the HbA1c level at 3
      months. The prediction of 3-month HbA1c using 7-day metabolomic profile and the
      suggested new criterion [3-HB]/[glucose] could augment current prognostic
      modalities and help clinicians decide if drug therapy is necessary. 

PMID- 25384028
TI  - Fluorescent non-peptidic RGD mimetics with high selectivity for alphaVbeta3 vs
      alphaIIbbeta3 integrin receptor: novel probes for in vivo optical imaging.
AB  - Integrins are heterodimeric transmembrane protein receptors consisting of
      different alpha and beta subunits. alpha(v)beta(3) integrins are overexpressed on
      many tumor cells and tumor-associated angiogenic vessels, whereas
      alpha(IIb)beta(3) is a receptor for, e.g., fibrinogen and mediates platelet
      aggregation. In this study, a near-infrared fluorescent imaging probe has been
      designed and synthesized by conjugating fluorescent dyes to a non-peptidic,
      pharmacophore-based ligand, based on a molecular modeling design approach.
      Affinity values were determined, and in vitro cell binding assays and preliminary
      in vivo xenograft studies in nude mice were performed to evaluate target binding.
      Competition assays revealed excellent binding and selectivity to alpha(v)beta(3)
      compared to that for alpha(IIb)beta(3). In vitro, the probe showed high target
      binding on alpha(v)beta(3)-positive M-21 cells and negligible binding to
      alpha(v)beta(3)-negative MCF-7 cells. In vivo, the tracer is able to image target
      expression in U-87 xenografts with a maximum signal-to-noise ratio (SNR) of 2.5:1
      at 24 h after injection.

PMID- 25384029
TI  - Challenges facing the finance reform of the health system in Chile.
AB  - Financing is one of the key functions of health systems, which includes the
      processes of revenue collection, fund pooling and acquisitions in order to ensure
      access to healthcare for the entire population. The article analyzes the
      financing model of the Chilean health system in terms of the first two processes,
      confirming low public spending on healthcare and high out-of-pocket expenditure,
      in addition to an appropriation of public resources by private insurers and
      providers. Insofar as pooling, there is lack of solidarity and risk sharing
      leading to segmentation of the population that is not consistent with the concept
      of social security, undermines equity and reduces system-wide efficiency. There
      is a pressing need to jumpstart reforms that address these issues. Treatments
      must be considered together with public health concerns and primary care in order
      to ensure the right to health of the entire population. 

PMID- 25384033
TI  - Experimental and theoretical investigation of the pyrolysis products of
      iminodiacetonitrile, (N=CCH2)2NH.
AB  - The gas-phase FTIR study of the pyrolysis products of iminodiacetonitrile,
      (N=CCH2)2NH has revealed the existence of C-cyanomethanimine, N=CCH?NH, and
      ketenimine, CH2?C?NH. The former has two isomers: Z and E; while the later
      readily taumerizes to acetonitrile, CH3C=N. A trapping/revaporization system has
      been used to purify C-cyanomethanimine. The analysis of the rotational structures
      of the IR medium resolution C-type CNH bend, nu6, and C?N torsional mode, nu10,
      has led to a conformational characterization of these isomers. The Z-isomer was
      shown to be the major product. This conjecture was supported by ab initio MO
      calculations that confirmed the relative total energy stability of the Z-isomer
      over its E-counterpart by 0.173 to 2.326 kJ/mol. The K values indicated that the
      equilibrium concentration of Z-C-cyanomethanimine amounts to up to three times
      that of E-C-cyanomethanimine. A further investigation using NBO technique proved
      the predilection of the Z-isomer. In addition it relates its provenance of
      preference to the remote nN6 -> sigma*C4-N5 interaction that stabilized it by
      1.10 kcal/mol. A thorough theoretical investigation of the tautomerization
      reaction between ketenimine and acetonitrile will be published in a separate
      contribution. 

PMID- 25384034
TI  - A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple
      negative breast cancer.
AB  - We investigated the application of a mimetic 20 amino acid peptide derived from
      type IV collagen for treatment of breast cancer. We showed that the peptide
      induced a decrease of proliferation, adhesion, and migration of endothelial and
      tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB
      231 xenograft growth by 75% relative to control when administered
      intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in
      vascular properties throughout the treatment using MRI and found that the
      vascular volume and permeability surface area product decreased significantly.
      The treatment also resulted in an increase of caspase-3 activity and in a
      reduction of microvascular density. The multiple mode of action of this peptide,
      i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a
      therapeutic agent as a monotherapy or in combination with other compounds. 

PMID- 25384035
TI  - Involvement of TNF-alpha converting enzyme in the development of psoriasis-like
      lesions in a mouse model.
AB  - TNF-alpha plays a crucial role in psoriasis; therefore, TNF inhibition has become
      a gold standard for the treatment of psoriasis. TNF-alpha is processed from a
      membrane-bound form by TNF-alpha converting enzyme (TACE) to soluble form, which
      exerts a number of biological activities. EGF receptor (EGFR) ligands, including
      heparin-binding EGF-like growth factor (HB-EGF), amphiregulin and transforming
      growth factor (TGF)-alpha are also TACE substrates and are psoriasis-associated
      growth factors. Vascular endothelial growth factor (VEGF), one of the downstream
      molecules of EGFR and TNF signaling, plays a key role in angiogenesis for
      developing psoriasis. In the present study, to assess the possible role of TACE
      in the pathogenesis of psoriasis, we investigated the involvement of TACE in TPA
      induced psoriasis-like lesions in K5.Stat3C mice, which represent a mouse model
      of psoriasis. In this mouse model, TNF-alpha, amphiregulin, HB-EGF and TGF-alpha
      were significantly up-regulated in the skin lesions, similar to human psoriasis.
      Treatment of K5.Stat3C mice with TNF-alpha or EGFR inhibitors attenuated the skin
      lesions, suggesting the roles of TACE substrates in psoriasis. Furthermore, the
      skin lesions of K5.Stat3C mice showed down-regulation of tissue inhibitor of
      metalloproteinase-3, an endogenous inhibitor of TACE, and an increase in soluble
      TNF-alpha. A TACE inhibitor abrogated EGFR ligand-dependent keratinocyte
      proliferation and VEGF production in vitro, suggesting that TACE was involved in
      both epidermal hyperplasia and angiogenesis during psoriasis development. These
      results strongly suggest that TACE contributes to the development of psoriatic
      lesions through releasing two kinds of psoriasis mediators, TNF-alpha and EGFR
      ligands. Therefore, TACE could be a potential therapeutic target for the
      treatment of psoriasis. 

PMID- 25384037
TI  - RApid Parallel Protein EvaluatoR (RAPPER), from gene to enzyme function in one
      day.
AB  - Cell-free transcription-translation systems offer an effective and versatile
      platform to explore the impact of genetic variations on protein function. We have
      developed a protocol for preparing linear, mutagenic DNA templates for direct use
      in the PURE system, enabling the fast and semi-quantitative evaluation of amino
      acid variations on catalytic activity and stereo-selectivity in native and
      engineered variants of Old Yellow Enzyme. 

PMID- 25384036
TI  - Contrasting effect of prepulse signals on performance of Toxoplasma-infected and
      Toxoplasma-free subjects in an acoustic reaction times test.
AB  - BACKGROUND: About 30% of people on Earth have latent toxoplasmosis. Infected
      subjects do not express any clinical symptoms, however, they carry dormant stages
      of parasite Toxoplasma for the rest of their life. This form of toxoplasmosis is
      mostly considered harmless, however, recent studies showed its specific effects
      on physiology, behaviour and its associations with various diseases, including
      psychiatric disorders such as schizophrenia. Individuals who suffer from
      schizophrenia have about 2.7 times higher prevalence of Toxoplasma-seropositivity
      than controls, which suggests that some traits characteristic of schizophrenic
      patients, including the sex difference in schizophrenia onset, decrease of grey
      matter density in specific brain areas and modification of prepulse inhibition of
      startle reaction could in fact be caused by toxoplasmosis for those patients who
      are Toxoplasma-seropositive. METHODOLOGY/PRINCIPAL FINDINGS: We measured the
      effect of prepulse inhibition/facilitation of the startle reaction on reaction
      times. The students, 170 women and 66 men, were asked to react as quickly as
      possible to a startling acoustic signal by pressing a computer mouse button. Some
      of the startling signals were without the prepulse, some were 20 msec. preceded
      by a short (20 msec.) prepulse signal of lower intensity. Toxoplasma-seropositive
      subjects had longer reaction times than the controls. Acoustic prepulse shorted
      the reaction times in all subjects. This effect of prepulse on reaction times was
      stronger in male subjects and increased with the duration of infection,
      suggesting that it represented a cumulative effect of latent toxoplasmosis,
      rather than a fading out after effect of past acute toxoplasmosis. CONCLUSIONS:
      Different sensitivity of Toxoplasma-seropositive and Toxoplasma-seronegative
      subjects on effect of prepulses on reaction times (the toxoplasmosis-prepulse
      interaction) suggested, but of course did not prove, that the alternations of
      prepulse inhibition of startle reaction observed in schizophrenia patients
      probably joined the list of schizophrenia symptoms that are in fact caused by
      latent toxoplasmosis.

PMID- 25384038
TI  - Zinc oxide nanoparticles cause inhibition of microbial denitrification by
      affecting transcriptional regulation and enzyme activity.
AB  - Over the past few decades, human activities have accelerated the rates and
      extents of water eutrophication and global warming through increasing delivery of
      biologically available nitrogen such as nitrate and large emissions of
      anthropogenic greenhouse gases. In particular, nitrous oxide (N2O) is one of the
      most important greenhouse gases, because it has a 300-fold higher global warming
      potential than carbon dioxide. Microbial denitrification is a major pathway
      responsible for nitrate removal, and also a dominant source of N2O emissions from
      terrestrial or aquatic environments. However, whether the release of zinc oxide
      nanoparticles (ZnO NPs) into the environment affects microbial denitrification is
      largely unknown. Here we show that the presence of ZnO NPs lead to great
      increases in nitrate delivery (9.8-fold higher) and N2O emissions (350- and 174
      fold higher in the gas and liquid phases, respectively). Our data further reveal
      that ZnO NPs significantly change the transcriptional regulations of glycolysis
      and polyhydroxybutyrate synthesis, which causes the decrease in reducing powers
      available for the reduction of nitrate and N2O. Moreover, ZnO NPs substantially
      inhibit the gene expressions and catalytic activities of key denitrifying
      enzymes. These negative effects of ZnO NPs on microbial denitrification finally
      cause lower nitrate removal and higher N2O emissions, which is likely to
      exacerbate water eutrophication and global warming. 

PMID- 25384039
TI  - Toxin-antitoxin systems in the mobile genome of Acidithiobacillus ferrooxidans.
AB  - Toxin-antitoxin (TA) systems are genetic modules composed of a pair of genes
      encoding a stable toxin and an unstable antitoxin that inhibits toxin activity.
      They are widespread among plasmids and chromosomes of bacteria and archaea. TA
      systems are known to be involved in the stabilization of plasmids but there is no
      consensus about the function of chromosomal TA systems. To shed light on the role
      of chromosomally encoded TA systems we analyzed the distribution and
      functionality of type II TA systems in the chromosome of two strains from
      Acidithiobacillus ferrooxidans (ATCC 23270 and 53993), a Gram-negative,
      acidophilic, environmental bacterium that participates in the bioleaching of
      minerals. As in other environmental microorganisms, A. ferrooxidans has a high
      content of TA systems (28-29) and in twenty of them the toxin is a putative
      ribonuclease. According to the genetic context, some of these systems are encoded
      near or within mobile genetic elements. Although most TA systems are shared by
      both strains, four of them, which are encoded in the active mobile element
      ICEAfe1, are exclusive to the type strain ATCC 23270. We demonstrated that two TA
      systems from ICEAfe1 are functional in E. coli cells, since the toxins inhibit
      growth and the antitoxins counteract the effect of their cognate toxins. All the
      toxins from ICEAfe1, including a novel toxin, are RNases with different ion
      requirements. The data indicate that some of the chromosomally encoded TA systems
      are actually part of the A. ferrooxidans mobile genome and we propose that could
      be involved in the maintenance of these integrated mobile genetic elements.

PMID- 25384040
TI  - Germ-line transmitted, chromosomally integrated HHV-6 and classical Hodgkin
      lymphoma.
AB  - A unique feature of both human herpesvirus 6A and B (HHV-6A and B) among human
      herpesviruses is their ability to integrate into chromosomal telomeres. In some
      individuals integrated viral genomes are present in the germ-line and result in
      the vertical transmission of HHV-6; however, little is known about the disease
      associations of germ-line transmitted, chromosomally integrated HHV-6 (ciHHV-6).
      Recent publications suggest that HHV-6 is associated with classical Hodgkin
      lymphoma (cHL). Here we examine the prevalence of ciHHV-6 in 936 cases of cHL and
      563 controls by screening with a duplex TaqMan assay and confirming with droplet
      digital PCR. ciHHV-6 was detected in 10/563 (1.8%) controls and in all but one
      individual the virus was HHV-6B. Amongst cases 16/936 (1.7%) harboured ciHHV-6,
      thus demonstrating no association between ciHHV-6 and risk of cHL. 

PMID- 25384041
TI  - Reduce temptation or resist it? Experienced temptation mediates the relationship
      between implicit evaluations of unhealthy snack foods and subsequent intake.
AB  - A more negative implicit evaluation of unhealthy food stimuli and a more positive
      implicit evaluation of a weight-management goal have been shown to predict lower
      consumption of unhealthy food. However, the associations between these
      evaluations, temptation to indulge and consumption of unhealthy food remain
      unclear. The current study investigated whether temptation would mediate the
      relationship between implicit food and goal evaluations and consumption
      (resembling an antecedent-focused route to self-control of eating), or whether
      those evaluations would moderate the relationship between temptation and
      consumption (resembling a response-focused route). A sample of 156 women (17-25
      years), who tried to manage their weight through healthy eating, completed two
      implicit association tasks assessing implicit food and goal evaluations,
      respectively. Intake of four energy-dense snack foods was measured in a task
      disguised as a taste test, and participants reported the strength of experienced
      temptation to indulge in the snacks offered. Negative implicit food evaluation
      was associated with lower snack intake, and temptation mediated this
      relationship. Implicit goal evaluation was unrelated to both temptation strength
      and snack consumption. The findings contribute to an understanding of how
      negative implicit unhealthy food evaluation relates to lower consumption, namely
      through the mediation of temptation to indulge in those foods.

PMID- 25384042
TI  - Effects of blood pressure and sex on the change of wave reflection: evidence from
      Gaussian fitting method for radial artery pressure waveform.
AB  - An early return of the reflected component in the arterial pulse has been
      recognized as an important indicator of cardiovascular risk. This study aimed to
      determine the effects of blood pressure and sex factor on the change of wave
      reflection using Gaussian fitting method. One hundred and ninety subjects were
      enrolled. They were classified into four blood pressure categories based on the
      systolic blood pressures (i.e., <= 110, 111-120, 121-130 and >= 131 mmHg). Each
      blood pressure category was also stratified for sex factor. Electrocardiogram
      (ECG) and radial artery pressure waveforms (RAPW) signals were recorded for each
      subject. Ten consecutive pulse episodes from the RAPW signal were extracted and
      normalized. Each normalized pulse episode was fitted by three Gaussian functions.
      Both the peak position and peak height of the first and second Gaussian
      functions, as well as the peak position interval and peak height ratio, were used
      as the evaluation indices of wave reflection. Two-way ANOVA results showed that
      with the increased blood pressure, the peak position of the second Gaussian
      significantly shorten (P < 0.01), the peak height of the first Gaussian
      significantly decreased (P < 0.01) and the peak height of the second Gaussian
      significantly increased (P < 0.01), inducing the significantly decreased peak
      position interval and significantly increased peak height ratio (both P < 0.01).
      Sex factor had no significant effect on all evaluation indices (all P > 0.05).
      Moreover, the interaction between sex and blood pressure factors also had no
      significant effect on all evaluation indices (all P > 0.05). These results showed
      that blood pressure has significant effect on the change of wave reflection when
      using the recently developed Gaussian fitting method, whereas sex has no
      significant effect. The results also suggested that the Gaussian fitting method
      could be used as a new approach for assessing the arterial wave reflection.

PMID- 25384043
TI  - Keratocytes derived from spheroid culture of corneal stromal cells resemble
      tissue resident keratocytes.
AB  - PURPOSE: Corneal stromal cells transform to precursor cells in spheroid culture.
      We determined whether keratocytes derived from spheroid culture of murine corneal
      stromal cells resemble tissue resident keratocytes. METHODS: Spheroid culture was
      performed by seeding dissociated stromal cells onto ultra-low attachment plates
      containing serum-free mesenchymal stem cell culture medium. Spheroids were
      characterized with phenotype specific markers and stemness transcription factor
      genes. Spheroids and adherent cells in culture were induced to differentiate to
      keratocytes using keratocyte induction medium (KIM) and compared with tissue
      resident keratocytes. RESULTS: Stromal cells formed spheroids in ultra-low
      attachment plates, but not in polystyrene tissue culture dishes. Keratocan
      expression and abundance was significantly higher in spheroids as compared to
      adherent cells whereas alpha-smooth muscle actin (alpha-SMA) was significantly
      lower. As compared to adherent culture-derived cells, the expressions of
      keratocan, aldehyde dehydrogenase (ALDH3A1) and alpha-SMA in spheroid-derived
      cells approximated much more closely the levels of these genes in tissue resident
      keratocytes. Of the stemness genes, Nanog and Oct4 were upregulated in the
      spheroids. CONCLUSION: Stemness transcription factor genes are upregulated in
      spheroids. Keratocytes derived from spheroids resemble tissue resident
      keratocytes, thus increasing manifolds the quantity of these cells for in-vitro
      experiments.

PMID- 25384044
TI  - Increased CD112 expression in methylcholanthrene-induced tumors in CD155
      deficient mice.
AB  - Tumor recognition by immune effector cells is mediated by antigen receptors and a
      variety of adhesion and costimulatory molecules. The evidence accumulated since
      the identification of CD155 and CD112 as ligands for DNAM-1 in humans and mice
      has suggested that the interactions between DNAM-1 and its ligands play an
      important role in T cell- and natural killer (NK) cell-mediated recognition and
      lysis of tumor cells. We have previously demonstrated that methylcholanthrane
      (MCA) accelerates tumor development in DNAM-1-deficient mice, and the Cd155 level
      on MCA-induced tumors is significantly higher in DNAM-1-deficient mice than in
      wild-type (WT) mice. By contrast, Cd112 expression on the tumors is similar in WT
      and DNAM-1-deficient mice, suggesting that CD155 plays a major role as a DNAM-1
      ligand in activation of T cells and NK cells for tumor immune surveillance. To
      address this hypothesis, we examined MCA-induced tumor development in CD155
      deficient mice. Unexpectedly, we observed no significant difference in tumor
      development between WT and CD155-deficient mice. Instead, we found that Cd112
      expression was significantly higher in the MCA-induced tumors of CD155-deficient
      mice than in those of WT mice. We also observed higher expression of DNAM-1 and
      lower expression of an inhibitory receptor, TIGIT, on CD8+ T cells in CD155
      deficient mice. These results suggest that modulation of the expression of
      receptors and CD112 compensates for CD155 deficiency in immune surveillance
      against MCA-induced tumors.

PMID- 25384045
TI  - An efficient ERP-based brain-computer interface using random set presentation and
      face familiarity.
AB  - Event-related potential (ERP)-based P300 spellers are commonly used in the field
      of brain-computer interfaces as an alternative channel of communication for
      people with severe neuro-muscular diseases. This study introduces a novel P300
      based brain-computer interface (BCI) stimulus paradigm using a random set
      presentation pattern and exploiting the effects of face familiarity. The effect
      of face familiarity is widely studied in the cognitive neurosciences and has
      recently been addressed for the purpose of BCI. In this study we compare P300
      based BCI performances of a conventional row-column (RC)-based paradigm with our
      approach that combines a random set presentation paradigm with (non-) self-face
      stimuli. Our experimental results indicate stronger deflections of the ERPs in
      response to face stimuli, which are further enhanced when using the self-face
      images, and thereby improving P300-based spelling performance. This lead to a
      significant reduction of stimulus sequences required for correct character
      classification. These findings demonstrate a promising new approach for improving
      the speed and thus fluency of BCI-enhanced communication with the widely used
      P300-based BCI setup. 

PMID- 25384046
TI  - Genomic assortative mating in marriages in the United States.
AB  - Assortative mating in phenotype in human marriages has been widely observed.
      Using genome-wide genotype data from the Framingham Heart study (FHS; number of
      married couples = 989) and Health Retirement Survey (HRS; number of married
      couples = 3,474), this study investigates genomic assortative mating in human
      marriages. Two types of genomic marital correlations are calculated. The first is
      a correlation specific to a single married couple "averaged" over all available
      autosomal single-nucleotide polymorphism (SNPs). In FHS, the average married
      couple correlation is 0.0018 with p = 3 * 10(-5); in HRS, it is 0.0017 with p =
      7.13 * 10(-13). The marital correlation among the positively assorting SNPs is
      0.001 (p = .0043) in FHS and 0.015 (p = 1.66 * 10(-24)) in HRS. The sizes of
      these estimates in FHS and HRS are consistent with what are suggested by the
      distribution of the allelic combination. The study also estimated SNP-specific
      correlation "averaged" over all married couples. Suggestive evidence is reported.
      Future studies need to consider a more general form of genomic assortment, in
      which different allelic forms in homologous genes and non-homologous genes result
      in the same phenotype.

PMID- 25384047
TI  - Salt-inducible kinase 1 (SIK1) is induced by gastrin and inhibits migration of
      gastric adenocarcinoma cells.
AB  - Salt-inducible kinase 1 (SIK1/Snf1lk) belongs to the AMP-activated protein kinase
      (AMPK) family of kinases, all of which play major roles in regulating metabolism
      and cell growth. Recent studies have shown that reduced levels of SIK1 are
      associated with poor outcome in cancers, and that this involves an invasive
      cellular phenotype with increased metastatic potential. However, the molecular
      mechanism(s) regulated by SIK1 in cancer cells is not well explored. The peptide
      hormone gastrin regulates cellular processes involved in oncogenesis, including
      proliferation, apoptosis, migration and invasion. The aim of this study was to
      examine the role of SIK1 in gastrin responsive adenocarcinoma cell lines AR42J,
      AGS-GR and MKN45. We show that gastrin, known to signal through the Gq/G11
      coupled CCK2 receptor, induces SIK1 expression in adenocarcinoma cells, and that
      transcriptional activation of SIK1 is negatively regulated by the Inducible cAMP
      early repressor (ICER). We demonstrate that gastrin-mediated signalling induces
      phosphorylation of Liver Kinase 1B (LKB1) Ser-428 and SIK1 Thr-182. Ectopic
      expression of SIK1 increases gastrin-induced phosphorylation of histone
      deacetylase 4 (HDAC4) and enhances gastrin-induced transcription of c-fos and CRE
      , SRE-, AP1- and NF-kappaB-driven luciferase reporter plasmids. We also show that
      gastrin induces phosphorylation and nuclear export of HDACs. Next we find that
      siRNA mediated knockdown of SIK1 increases migration of the gastric
      adenocarcinoma cell line AGS-GR. Evidence provided here demonstrates that SIK1 is
      regulated by gastrin and influences gastrin elicited signalling in gastric
      adenocarcinoma cells. The results from the present study are relevant for the
      understanding of molecular mechanisms involved in gastric adenocarcinomas. 

PMID- 25384049
TI  - Biomechanical comparison of ponte osteotomy and discectomy.
AB  - STUDY DESIGN: Biomechanical cadaver study. OBJECTIVE: To evaluate the relative
      effectiveness of Ponte osteotomies for spinal release in deformity correction.
      SUMMARY OF BACKGROUND DATA: Controversy exists as to the role of Ponte osteotomy
      in deformity correction surgery. Very little has been written about the
      biomechanical effects of Ponte osteotomy. Past biomechanical studies have been
      limited to application of forces through endplates, single functional units, or
      lack of comparison with anterior release. METHODS: Twelve fresh-frozen human full
      thoracic spinal units were tested for motion in axial rotation,
      flexion/extension, and lateral bending in a custom-designed robotic environment.
      Testing was repeated after sequential facetectomy and Ponte osteotomy (6
      specimens) and compared with partial and full discectomy (6 specimens). RESULTS:
      Motion in axial rotation is increased 21% by Ponte osteotomy compared with 35%
      for full discectomy. Anterior displacement of the spinal column, creating
      lordosis, was increased 15% by Ponte osteotomy and 40% by full discectomy.
      Posterior displacement of the spinal column, creating kyphosis, was increased 23%
      by Ponte osteotomy and 89% by full discectomy. Finally, in coronal force
      application the Ponte osteotomy had virtually no effect (2%) compared with 40%
      increased motion by full discectomy. CONCLUSION: Posterior Ponte osteotomy
      releases produced more motion than facetectomy alone in axial rotation and
      sagittal correction maneuvers, but had no effect on coronal correction. Anterior
      discectomy release destabilized spinal column significantly more than posterior
      releases in all force applications. Despite ample clinical experience
      demonstrating the effectiveness of posterior-only surgery, the biomechanical
      effect of Ponte osteotomies is modest. LEVEL OF EVIDENCE: N/A.

PMID- 25384050
TI  - How does free rod-sliding affect the posterior instrumentation for a dynamic
      stabilization using a bovine calf model?
AB  - STUDY DESIGN: A biomechanical cadaveric study in lumbar calf spine. OBJECTIVE:
      Evaluation of the effects of selected degrees of freedom (df) on the dynamic
      stabilization of the spine in terms of segmental range of motion (RoM), center of
      rotation (CoR), and implant loadings. SUMMARY OF BACKGROUND DATA: For dorsal
      stabilization, rigid implant systems are becoming increasingly complemented by
      numerous dynamic systems based on pedicle screws and varying df. However, it is
      still unclear which df is most suitable to accomplish a physiologically related
      dynamic stabilization, and which loadings are induced to the implants. Human and
      calf specimens are reported to show certain similarities in their biomechanics.
      Young healthy calf specimens are not degenerated and show less interindividual
      differences than elderly human specimens. However, the existing differences
      between species limit the conclusions in a preclinical setting. METHODS: Six calf
      specimens from level L3-L4 were analyzed in flexion and extension with a 6-df
      robotic spine simulator. A clinical functional radiological examination tool was
      used and parameters such as RoM, CoR, and implant loadings were determined for 6
      configurations: (1) intact, (2) defect, (3) rigid fixation, (4) free craniocaudal
      (CC) rod-sliding, (5) free polyaxiality, and (6) combined free rod-sliding and
      free polyaxiality. The location of the CoR was determined relative to vertebral
      body dimensions. A CoR repositioning was defined as sufficient when its median
      differed less than 5% of the vertebral body dimensions. RESULTS: Free rod-sliding
      in the CC direction restored the CoR from the defect back to the intact
      condition. The RoM could be significantly reduced to approximately 1/2 of the
      intact condition. Compared with the rigid condition, the implant bending moments
      increased from 0.3/-0.8 Nm (flexion/extension) to 1.3/-1.2 Nm for the free CC rod
      sliding condition. CONCLUSION: Free CC rod-sliding restores the intact conditions
      of the tested kinematic parameters most suitably and at the same time reduces the
      RoM. Stabilization toward the intact condition could decrease the risk of stress
      shielding and the progress of segment degeneration. LEVEL OF EVIDENCE: N/A.

PMID- 25384048
TI  - Health behaviour in children and adolescents with type 1 diabetes compared to a
      representative reference population.
AB  - OBJECTIVE: We provide a population-based overview of health behaviours of
      children and adolescents with type 1 diabetes in comparison to the general
      population, and analyse their relevance for glycaemic control and self-rated
      health status. METHODS: Data from questionnaires of 11- to 17-year-old children
      and adolescents with diabetes (n = 629) were compared to a representative sample
      (n = 6,813). RESULTS: Children and adolescents with type 1 diabetes had a
      significantly increased odds of infrequent physical activity (adjusted OR 1.56),
      short overall duration of physical activity per week (OR 1.55, difference -1.3
      hours/week), and high daily computer use (OR 2.51). They had a lower odds of
      active and passive smoking (OR 0.31 and OR 0.29), and high daily television time
      (OR 0.68). The odds of an at least good and excellent self-rated health status
      was increased with intense physical activity, and decreased with active smoking
      and prolonged daily use of computer and television. Active smoking and prolonged
      daily use of computer were associated with higher HbA1c. CONCLUSIONS: Children
      and adolescents with type 1 diabetes showed a different profile of health
      behaviour. Their overall health may improve if their education stresses
      specifically frequent physical activity with longer overall duration and less
      frequent television or computer use.

PMID- 25384051
TI  - Influence of pain sensitivity on surgical outcomes after lumbar spine surgery in
      patients with lumbar spinal stenosis.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: To assess the influence
      of pain sensitivity on surgical outcomes after lumbar spine surgery in patients
      with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: No previous study
      has investigated the relationship between the surgical outcomes for LSS and pain
      sensitivity questionnaire (PSQ) scores. METHODS: The study included 171 patients
      who were scheduled to undergo spine surgery for LSS. On the basis of their PSQ
      scores, patients were assigned to either a low (PSQ score<6.5, n=87) or high PSQ
      group (PSQ score>=6.5, n=84). The primary outcome was the Oswestry Disability
      Index (ODI) at 12 months after surgery. RESULTS: The ODI at 12 months after
      surgery was significantly lower in the low PSQ group than in the high PSQ group.
      Twelve months after surgery, the mean ODI scores (95% confidence interval) in the
      low and high PSQ groups were 21.1 (16.8-25.5) and 29.6 (25.0-34.1), respectively.
      The difference (95% confidence interval) in the ODI between the 2 groups was 3.2
      (-14.7 to -2.2) (P=0.009). There were significant differences in the secondary
      endpoints, including the ODI and visual analogue scale (VAS) scores for back and
      leg pain, in the follow-up assessments during a 12-month period after surgery,
      between the 2 groups (PSQ group; P<0.001 for the ODI, VAS score for back pain,
      and VAS score for leg pain). However, the patterns of changes of the ODI and VAS
      scores for back pain and leg pain in the follow-up assessments during a 12-month
      period were not significantly different (interaction between the PSQ group and
      follow-up assessment time; P=0.757, 0.126, and 0.950, respectively). CONCLUSION:
      Patients with high pain sensitivity may display less improvement in back pain,
      leg pain, and disability after surgery for LSS compared with patients with low
      pain sensitivity. Furthermore, the PSQ can be used to predict surgical outcomes
      after spine surgery for LSS. LEVEL OF EVIDENCE: 2.

PMID- 25384052
TI  - Work-related risk factors for neck pain in the US working population.
AB  - STUDY DESIGN: This study uses the Taylor linearized variance estimation method to
      compute weighted unadjusted and adjusted prevalence of neck pain by occupation,
      with a cross-section data set from the 2009 to 2012 National Health Interview
      Survey. OBJECTIVE: The goal of this study was to explore occupational patterns of
      neck pain and the relationship between long work hours and neck pain in the
      working population in the United States. SUMMARY OF BACKGROUND DATA: The past
      research has demonstrated that specific occupations have a high prevalence of
      neck pain. However, occupational patterns of neck pain in the United States have
      been understudied. METHODS: Risk of neck pain was estimated using univariate and
      multivariate logistic regression with odds ratios (ORs) with 95% confidence
      interval (CI) as measures of association. RESULTS: After controlling for
      demographic, socioeconomic status, and behavior-related factors and compared with
      workers in architecture and engineering occupation group, the top 5 occupational
      groups with significantly higher relative prevalence of neck pain included:
      military specific (OR, 2.50; 95% CI, 1.17-5.35); arts, design, entertainment,
      sports, and media (OR, 1.70; 95% CI, 1.34-2.17); life, physical, and social
      science (OR, 1.67; 95% CI, 1.33-2.11); health care support (OR, 1.55; 95% CI,
      1.23-1.97); and installation, maintenance, and repair (OR, 1.54; 95% CI, 1.21
      1.96). Compared with those who worked 40 hours, people who worked 46 to 59 hours
      (OR, 1.20; 95% CI, 1.10-1.30) and 60 or more hours of work per week (OR, 1.35;
      95% CI-1.21, 1.51) were more likely to report neck pain. CONCLUSION: This study
      adds to the evidence that an individual's occupation and work hours affect
      workers' risk for neck pain. This study indicates a need for new research efforts
      and public policies targeted to workers who are susceptible to neck pain in the
      United States. LEVEL OF EVIDENCE: 1.

PMID- 25384053
TI  - Transcranial magnetic stimulation in the diagnosis of cervical compressive
      myelopathy: comparison with spinal cord evoked potentials.
AB  - STUDY DESIGN: Single-center retrospective study. OBJECTIVE: To reveal the
      characteristic changes in central motor conduction time (CMCT) produced by
      transcranial magnetic stimulation among the responsible levels of cervical
      compressive myelopathy (CCM). SUMMARY OF BACKGROUND DATA: CMCT is a useful and
      noninvasive measure for evaluating the central motor pathway. However, a
      systematic correlation between CMCT findings and the responsible level of CCM has
      so far not been addressed in a large patient cohort. METHOD: We measured CMCT in
      75 patients with CCM who were determined by intraoperative spinal cord evoked
      potentials to have a single site of conduction abnormality at the intervertebral
      level. Twenty-one healthy controls were also evaluated. Motor evoked potentials,
      compound muscle action potentials, and F wave were recorded from bilateral
      abductor digiti minimi (ADM) and abductor hallucis (AH) muscles. CMCT was
      calculated as follows: motor evoked potentials latency-(CMAPs latency+F latency
      1)/2 (ms). RESULT: The mean values of ADM-CMCT and AH-CMCT at each responsible
      level were significantly longer than those of normal values (P<0.01). However,
      the mean value of ADM-CMCT at the C6-C7 level was markedly shorter than those at
      the other levels, whereas the mean values of AH-CMCT were not significantly
      different between each responsible level. We determined that an ADM-CMCT longer
      than 7.9 ms (mean+2.5 standard deviation) was abnormal. Using this definition,
      the sensitivity of ADM-CMCT for CCM was 92% for C3-C4 myelopathy, 95% for C4-C5,
      58% for C5-C6, and 9% for C6-C7. CONCLUSION: ADM-CMCT is useful for the screening
      of CCM rostral to the C5-C6 level. Diagnosis of patients with C6-C7 myelopathy
      should include assessment of the AH-CMCT. LEVEL OF EVIDENCE: 4.

PMID- 25384054
TI  - Role of 18F-fluoro-D-deoxyglucose PET/CT in diagnosing surgical site infection
      after spine surgery with instrumentation.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To investigate the
      effectiveness of positron emission tomography/computed tomography (PET/CT) in
      diagnosing surgical site infection (SSI) after spinal surgery with
      instrumentation. SUMMARY OF BACKGROUND DATA: Several reports have indicated the
      usefulness of F-fluoro-D-deoxyglucose (F-18 FDG) PET in detecting sites of
      infection including spinal infection sites. However, no report has documented the
      efficacy of PET/CT in detecting SSI after spinal surgery with instrumentation.
      METHODS: A total of 811 consecutive case patients who underwent minimally
      invasive posterior lumbar interbody fusion surgery with instrumentation from
      December 2008 to February 2012 were enrolled. Of these, for all case patients
      clinically suspected as having SSI by laboratory data and clinical symptoms,
      PET/CT was performed. Six patients with no apparent sign of SSI served as a
      control group. Image data were evaluated by 2 nuclear medicine physicians blinded
      to the clinical and pathological results. The data were quantitatively analyzed
      by the maximum standardized uptake value as an index of F-18 FDG uptake. RESULTS:
      Visual assessment by PET/CT revealed that all 8 patients with suspected SSI were
      positive for infection whereas all 6 controls without apparent infection were
      negative for infection. There was a statistically significant difference in the
      maximum standardized uptake values (mean and range) between the SSI and control
      groups (9.0 and 5.5-14.7 vs. 3.3 and 2.0-4.3, respectively; P = 0.003). All 8
      patients underwent surgical debridement with selective implant removal and
      achieved a good clinical course. CONCLUSION: PET/CT was effective in diagnosing
      SSI and identifying infection sites despite the presence of spinal instruments.
      Although further studies with a larger number of patients are required, PET/CT
      presents a good candidate for detecting early-phase SSI after instrumented spinal
      surgery.

PMID- 25384055
TI  - Rheumatoid arthritis-induced lateral atlantoaxial subluxation with multiple
      vertebrobasilar infarctions.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To highlight the probability that lateral
      atlantoaxial subluxation (AAS) exists in patients with rheumatoid arthritis (RA)
      and induces vertebrobasilar infarctions that are more foregrounded than
      compressive myelopathy. SUMMARY OF BACKGROUND DATA: Although lateral subluxation
      is a well-known subtype of AAS, a case of cerebral ischemia associated with
      lateral AAS has not been reported before. METHODS: A 52-year-old male with a 6
      year history of RA had a sudden onset of visual field defect and mild right
      cerebellar ataxia. Head magnetic resonance imaging revealed acute multiple
      infarctions in the vertebrobasilar area, and magnetic resonance angiography
      revealed stenosis of the left vertebral artery (VA). Lateral radiograph of the
      cervical spine in the neutral position revealed atlanto-occipital assimilation
      and anterior AAS. T2-weighted sagittal images on cervical magnetic resonance
      imaging revealed high signal intensity in the spinal cord at C1-C2. Cerebral
      angiography revealed right VA occlusion and severe stenosis of the left V3
      segment of VA. Three-dimensional computed tomography angiography of the
      craniovertebral junction revealed lateral AAS, which was due to severe erosive
      changes of the facet joints, and the left V3 portion was stenosed by a bony
      component. During conservative therapy, the patient experienced left occulomotor
      nerve palsy due to a second stroke. RESULTS: Two months later, the patient
      underwent occipitocervical posterior fusion with an iliac bone graft. His
      postoperative course was uneventful, and the left VA stenosis disappeared. At the
      45-month follow-up, he had no further infarctions. Bony fusion was radiologically
      confirmed, and 3-dimensional computed tomography angiography revealed good
      patency of the affected left VA. CONCLUSION: In patients with RA, the potential
      risk of AAS should be recognized. Lateral AAS in particular may induce cerebral
      ischemia by positional VA occlusion in advanced stages of the disease. LEVEL OF
      EVIDENCE: N/A.

PMID- 25384056
TI  - Evidence of polyethylene biodegradation by bacterial strains from the guts of
      plastic-eating waxworms.
AB  - Polyethylene (PE) has been considered nonbiodegradable for decades. Although the
      biodegradation of PE by bacterial cultures has been occasionally described, valid
      evidence of PE biodegradation has remained limited in the literature. We found
      that waxworms, or Indian mealmoths (the larvae of Plodia interpunctella), were
      capable of chewing and eating PE films. Two bacterial strains capable of
      degrading PE were isolated from this worm's gut, Enterobacter asburiae YT1 and
      Bacillus sp. YP1. Over a 28-day incubation period of the two strains on PE films,
      viable biofilms formed, and the PE films' hydrophobicity decreased. Obvious
      damage, including pits and cavities (0.3-0.4 MUm in depth), was observed on the
      surfaces of the PE films using scanning electron microscopy (SEM) and atomic
      force microscopy (AFM). The formation of carbonyl groups was verified using X-ray
      photoelectron spectroscopy (XPS) and microattenuated total reflectance/Fourier
      transform infrared (micro-ATR/FTIR) imaging microscope. Suspension cultures of
      YT1 and YP1 (10(8) cells/mL) were able to degrade approximately 6.1 +/- 0.3% and
      10.7 +/- 0.2% of the PE films (100 mg), respectively, over a 60-day incubation
      period. The molecular weights of the residual PE films were lower, and the
      release of 12 water-soluble daughter products was also detected. The results
      demonstrated the presence of PE-degrading bacteria in the guts of waxworms and
      provided promising evidence for the biodegradation of PE in the environment. 

PMID- 25384058
TI  - Beta diversity of plant-pollinator networks and the spatial turnover of pairwise
      interactions.
AB  - Interactions between species form complex networks that vary across space and
      time. Even without spatial or temporal constraints mutualistic pairwise
      interactions may vary, or rewire, across space but this variability is not well
      understood. Here, we quantify the beta diversity of species and interactions and
      test factors influencing the probability of turnover of pairwise interactions
      across space. We ask: 1) whether beta diversity of plants, pollinators, and
      interactions follow a similar trend across space, and 2) which interaction
      properties and site characteristics are related to the probability of turnover of
      pairwise interactions. Geographical distance was positively correlated with plant
      and interaction beta diversity. We find that locally frequent interactions are
      more consistent across space and that local flower abundance is important for the
      realization of pairwise interactions. While the identity of pairwise interactions
      is highly variable across space, some species-pairs form interactions that are
      locally frequent and spatially consistent. Such interactions represent
      cornerstones of interacting communities and deserve special attention from
      ecologists and conservation planners alike. 

PMID- 25384057
TI  - Targeted decationized polyplexes for siRNA delivery.
AB  - The applicability of small interfering RNA (siRNA) in future therapies depends on
      the availability of safe and efficient carrier systems. Ideally, siRNA delivery
      requires a system that is stable in the circulation but upon specific uptake into
      target cells can rapidly release its cargo into the cytoplasm. Previously, we
      evaluated a novel generation of carrier systems ("decationized" polyplexes) for
      DNA delivery, and it was shown that folate targeted decationized polyplexes had
      an excellent safety profile and showed intracellular triggered release upon cell
      specific uptake. Targeted decationized polyplexes consist of a core of disulfide
      cross-linked poly(hydroxypropyl methacrylamide) (pHPMA) stably entrapping nucleic
      acids and a shell of poly(ethylene glycol) (PEG) decorated with folate molecules.
      In the present study, the applicability of folate targeted decationized
      polyplexes for siRNA delivery was investigated. This required optimization of the
      carrier system particularly regarding the cross-linking density of the core of
      the polyplexes. Stable and nanosized siRNA decationized polyplexes were
      successfully prepared by optimizing the cross-link density of their core. Upon
      incubation in human plasma, a significant portion of siRNA remained entrapped in
      the decationized polyplexes as determined by fluorescence correlation
      spectroscopy (FCS). When tested in a folate receptor overexpressing cell line
      stably expressing luciferase, Skov3-luc, sequence specific gene silencing was
      observed. As expected, neither interference on the intrinsic luciferase
      expression nor on the cell metabolic activity (determined by XTT) was induced by
      the free-polymer or the siRNA polyplexes. In conclusion, targeted decationized
      polyplexes are safe and stable carriers that interact with the targeted cells and
      rapidly disassemble upon cell entry making them promising siRNA delivery systems.

PMID- 25384059
TI  - Diversification versus specialization in complex ecosystems.
AB  - By analyzing the distribution of revenues across the production sectors of quoted
      firms we suggest a novel dimension that drives the firms diversification process
      at country level. Data show a non trivial macro regional clustering of the
      diversification process, which underlines the relevance of geopolitical
      environments in determining the microscopic dynamics of economic entities. These
      findings demonstrate the possibility of singling out in complex ecosystems those
      micro-features that emerge at macro-levels, which could be of particular
      relevance for decision-makers in selecting the appropriate parameters to be acted
      upon in order to achieve desirable results. The understanding of this micro-macro
      information exchange is further deepened through the introduction of a simplified
      dynamic model. 

PMID- 25384060
TI  - Acid sphingomyelinase serum activity predicts mortality in intensive care unit
      patients after systemic inflammation: a prospective cohort study.
AB  - INTRODUCTION: Acid sphingomyelinase is involved in lipid signalling pathways and
      regulation of apoptosis by the generation of ceramide and plays an important role
      during the host response to infectious stimuli. It thus has the potential to be
      used as a novel diagnostic marker in the management of critically ill patients.
      The objective of our study was to evaluate acid sphingomyelinase serum activity
      (ASM) as a diagnostic and prognostic marker in a mixed intensive care unit
      population before, during, and after systemic inflammation. METHODS: 40 patients
      admitted to the intensive care unit at risk for developing systemic inflammation
      (defined as systemic inflammatory response syndrome plus a significant
      procalcitonin [PCT] increase) were included. ASM was analysed on ICU admission,
      before (PCT before), during (PCT peak) and after (PCT low) onset of SIRS.
      Patients undergoing elective surgery served as control (N = 8). Receiver
      operating characteristics curves were computed. RESULTS: ASM significantly
      increased after surgery in the eight control patients. Patients from the
      intensive care unit had significantly higher ASM on admission than control
      patients after surgery. 19 out of 40 patients admitted to the intensive care unit
      developed systemic inflammation and 21 did not, with no differences in ASM
      between these two groups on admission. In patients with SIRS and PCT peak, ASM
      between admission and PCT before was not different, but further increased at PCT
      peak in non-survivors and was significantly higher at PCT low compared to
      survivors. Survivors exhibited decreased ASM at PCT peak and PCT low. Receiver
      operating curve analysis on discrimination of ICU mortality showed an area under
      the curve of 0.79 for ASM at PCT low. CONCLUSIONS: In summary, ASM was generally
      higher in patients admitted to the intensive care unit compared to patients
      undergoing uncomplicated surgery. ASM did not indicate onset of systemic
      inflammation. In contrast to PCT however, it remained high in non-surviving ICU
      patients after systemic inflammation.

PMID- 25384062
TI  - Dinuclear nickel(II) complexes with 2,5-diamino-1,4-benzoquinonediimine ligands
      as precatalysts for the polymerization of styrene: electronic and steric
      substituent effects.
AB  - Catalytic polymerization of styrene with a series of dinuclear nickel(II)
      complexes [{Ni(acac)}2{MU-C6H2-(N-Ph-R)4}] (R = 4-Et (1a), 4-OEt (1b), 2-OEt
      (1c), 2-Et (1d), and 2,6-Et2 (1e)) in the presence of methylaluminoxane was
      studied under various conditions to evaluate the substituent effect. The activity
      of 1a-1e, except 1c, increased with an increase in the reaction temperature, and
      the highest activity (7.46 * 10(5) g PS mol(-1) Ni h(-1)) was obtained using 1e
      at 70  degrees C. The electronic and steric properties of the ligand influenced
      the activity at room temperature, 50  degrees C, and 60  degrees C, steric
      factors barely, whereas electronic factors slightly dominated the activity at 70 
      degrees C. The activity with 1c remained constant at all temperatures, probably
      due to the masking of the active center by the formation of inactive N,N',O
      chelate species. The obtained polymers were atactic polystyrenes with molecular
      weights and molecular weight distributions in the range of 15,000-43,400 and 1.71
      2.14, respectively. While a clear dependence of the molecular weight and
      molecular weight distribution on the temperature was observed, no significant
      dependence on the substituent was noted.

PMID- 25384061
TI  - Dual regulation of myocardin expression by tumor necrosis factor-alpha in
      vascular smooth muscle cells.
AB  - De-differentiation of vascular smooth muscle cells (VSMCs) plays a critical role
      in the development of atherosclerosis, a chronic inflammatory disease involving
      various cytokines such as tumor necrosis factor-alpha (TNFalpha). Myocardin is a
      co-factor of serum response factor (SRF) and is considered to be the master
      regulator of VSMC differentiation. It binds to SRF and regulates the expression
      of contractile proteins in VSMCs. Myocardin is also known to inhibit VSMC
      proliferation by inhibiting the NF-kappaB pathway, whereas TNFalpha is known to
      activate the NF-kappaB pathway in VSMCs. NF-kappaB activation has also been shown
      to inhibit myocardin expression and smooth muscle contractile marker genes.
      However, it is not definitively known whether TNFalpha regulates the expression
      and activity of myocardin in VSMCs. The current study aimed to investigate the
      role of TNFalpha in regulating myocardin and VSMC function. Our studies showed
      that TNFalpha down-regulated myocardin expression and activity in cultured VSMCs
      by activating the NF-kappaB pathway, resulting in decreased VSMC contractility
      and increased VSMC proliferation. Surprisingly, we also found that TNFalpha
      prevented myocardin mRNA degradation, and resulted in a further significant
      increase in myocardin expression and activity in differentiated VSMCs. Both the
      NF-kappaB and p44/42 MAPK pathways were involved in TNFalpha regulation of
      myocardin, which further increased the contractility of VSMCs. These differential
      effects of TNFalpha on myocardin seemingly depended on whether VSMCs were in a
      differentiated or de-differentiated state. Taken together, our results
      demonstrate that TNFalpha differentially regulates myocardin expression and
      activity, which may play a key role in regulating VSMC functions. 

PMID- 25384063
TI  - Significance of programmed cell death-ligand 1 expression and its association
      with survival in patients with small cell lung cancer.
AB  - BACKGROUND: Programmed cell death 1 receptor-ligand interaction is a major
      pathway often hijacked by tumors to suppress immune control. The aim of this
      retrospective study was to investigate the prevalence and prognostic roles of
      programmed cell death -ligand 1 (PD-L1) expression in small cell lung cancer
      (SCLC). METHODS: The expression of PD-L1 was evaluated by immunohistochemical
      analysis in 102 specimens of SCLC. Tumors with staining in over 5% of tumor cells
      were scored as positive for PD-L1 expression. Survival analysis was performed
      using the Kaplan-Meier method. RESULTS: Expression of PD-L1 in tumor cells was
      observed in 71.6% (73 of 102) of SCLCs, and was significantly correlated with a
      limited disease (LD) stage. SCLC patients with PD-L1-positive tumors showed
      significantly longer overall survival (OS) than those with PD-L1-negative (median
      OS, 16.3 versus 7.3 months; p < 0.001, respectively). Multivariate analyses
      demonstrated that a good performance status, LD stage, and expression of PD-L1
      were significantly predictive of better OS, independently of other factors. We
      found no relevance between PD-L1 expression and progression-free survival for
      first-line treatment in LD- and extensive disease-SCLC patients. CONCLUSIONS: In
      patients with SCLC, expression of PD-L1 is positively correlated with a LD stage,
      and is independently predictive of a favorable outcome.

PMID- 25384065
TI  - A field evaluation of the Eye-Closure Interview with witnesses of serious crimes.
AB  - Laboratory research shows that eye-closure during memory retrieval improves both
      the amount and the factual accuracy of memory reports about witnessed events.
      Based on these findings, we developed the Eye-Closure Interview, and examined its
      feasibility (in terms of compliance with the instructions) and effectiveness (in
      terms of the quantity and quality of reported information) in eyewitness
      interviews conducted by the South African Police Service. Police interviewers
      from the Facial Identification Unit were randomly assigned to receive Eye-Closure
      Interview training or no training. We analyzed 95 interviews with witnesses of
      serious crimes (including robbery, rape, and murder), some of whom were
      instructed to close their eyes during salient parts of the interview. Witnesses
      in the control condition rarely spontaneously closed their eyes, but witnesses in
      the Eye-Closure Interview condition kept their eyes closed during 97% of their
      descriptions, suggesting that the Eye-Closure Interview would be easy to
      implement in a field setting. Although witnesses who closed their eyes did not
      remember more information overall, the information they provided was considered
      to be of significantly greater forensic relevance (as reflected in 2 independent
      blind assessments, 1 by a senior police expert and 1 by a senior researcher).
      Thus, based on the findings from this field study and from previous laboratory
      research, we conclude that implementation of the Eye-Closure Interview in witness
      interviews would help police interviewers to elicit more valuable information
      from witnesses, which could be relevant to the police investigation and/or in
      court. (PsycINFO Database Record 

PMID- 25384066
TI  - Catalytic [2 + 2 + 2] cycloaddition of benzothiophene dioxides with alpha,omega
      diynes for the synthesis of condensed polycyclic compounds.
AB  - A Rh-catalyzed intermolecular [2 + 2 + 2] cycloaddition of the 2,3-double bond of
      benzothiophene dioxides with alpha,omega-diynes gave sulfone-containing
      cycloadducts in high yields. This is the first example of a catalytic [2 + 2 + 2]
      cycloaddition that uses the 2,3-double bond of a heterole as an ene moiety. The
      consecutive reaction of benzodithiophene tetraoxide with 2,3-naphthylene-tethered
      1,7-diyne gave an 11-ring condensed polycyclic compound in one pot. 

PMID- 25384064
TI  - Postoperative radiotherapy is associated with better survival in non-small cell
      lung cancer with involved N2 lymph nodes: results of an analysis of the National
      Cancer Data Base.
AB  - INTRODUCTION: Use of postoperative radiotherapy (PORT) in non-small-cell lung
      cancer remains controversial. Limited data indicate that PORT may benefit
      patients with involved N2 nodes. This study evaluates this hypothesis in a large
      retrospective cohort treated with chemotherapy and contemporary radiation
      techniques. METHODS: The National Cancer Data Base was queried for patients
      diagnosed 2004-2006 with resected non-small-cell lung cancer and pathologically
      involved N2 (pN2) nodes also treated with chemotherapy. Multivariable Cox
      proportional hazards model was used to assess factors associated with overall
      survival (OS). Inverse probability of treatment weighting (IPTW) using the
      propensity score was used to reduce selection bias. OS was compared between
      patients treated with versus without PORT using the adjusted Kaplan-Meier
      estimator and weighted log-rank test based on IPTW. RESULTS: Two thousand and one
      hundred and fifteen patients were eligible for analysis. 918 (43.4%) received
      PORT, 1197 (56.6%) did not. PORT was associated with better OS (median survival
      time 42 months with PORT versus 38 months without, p = 0.048). This effect was
      significant in multivariable and IPTW Cox models (hazard ratio: 0.87, 95%
      confidence interval: 0.78-0.98, p = 0.026, and hazard ratio: 0.89, 95% confidence
      interval: 0.79-1.00, p = 0.046, respectively). No interaction was seen between
      the effects of PORT and number of involved lymph nodes (p = 0.615). CONCLUSIONS:
      PORT was associated with better survival for patients with pN2 nodes also treated
      with chemotherapy. No interaction was seen between benefit of PORT and number of
      involved nodes. These findings reinforce the benefit of PORT for N2 disease in
      modern practice using the largest, most recent cohort of chemotherapy-treated pN2
      patients to date.

PMID- 25384067
TI  - Morbidity and chronic pain following different techniques of caesarean section: A
      comparative study.
AB  - Research examining long-term outcomes after childbirth performed with different
      techniques of caesarean section have been limited and do not provide information
      on morbidity and neuropathic pain. The study compares two groups of patients
      submitted to the 'Traditional' method using Pfannenstiel incision and patients
      submitted to the 'Misgav Ladach' method >= 5 years after the operation. We find
      better long-term postoperative results in the patients that were treated with the
      Misgav Ladach method compared with the Traditional method. The results were
      statistically better regarding the intensity of pain, presence of neuropathic and
      chronic pain and the level of satisfaction about cosmetic appearance of the scar.

PMID- 25384068
TI  - Neural indicators of error processing in generalized anxiety disorder, obsessive
      compulsive disorder, and major depressive disorder.
AB  - The ability to detect and respond to errors is critical to successful adaptation
      to a changing environment, and variation in error-related brain activity has been
      linked to psychopathology. The error-related negativity (ERN), an event-related
      potential component, represents a unique neural response to errors and is
      generated in the anterior cingulate cortex (ACC). In the present study, we
      measured the ERN in a sample of individuals with Generalized Anxiety Disorder
      (GAD), Obsessive Compulsive Disorder (OCD), Major Depressive Disorder (MDD), or
      some combination of the 3. Also included were 56 healthy control participants.
      Consistent with previous research, a diagnosis of GAD, only in the absence of a
      comorbid diagnosis of depression, was characterized by a larger ERN than
      controls. No such enhancement was evident in the depressed group, or the comorbid
      group, suggesting comorbid depression may eliminate the relationship between the
      ERN and GAD. Across all groups, symptoms of checking were associated with a
      larger ERN, whereas symptoms of psychomotor retardation were associated with a
      smaller ERN. The results of the present study indicate that interactions among
      transdiagnostic dimensions will likely need to be considered in the creation of
      neurobiologically informed classification schemes.

PMID- 25384069
TI  - Anhedonia as a component of the tobacco withdrawal syndrome.
AB  - Animal research suggests that anhedonia is a tobacco withdrawal symptom, but this
      topic has not been addressed definitively in research with humans. This research
      sought to determine whether anhedonia is (a) an element of the tobacco withdrawal
      syndrome in humans and (b) an impediment to successful tobacco cessation. Data
      were from 1,175 smokers (58.3% women; 85.5% White) participating in a randomized
      double-blind, placebo-controlled trial of smoking cessation pharmacotherapies.
      Ecological momentary assessments for 5 days before and 10 days after the target
      quit day were used to assess anhedonia and other established withdrawal symptoms.
      Consistent with drug withdrawal, anhedonia showed an inverted-U pattern of change
      in response to tobacco cessation and was associated with the severity of other
      withdrawal symptoms and tobacco dependence. Postquit anhedonia was associated
      with decreased latency to relapse (hazard ratio = 1.09, 95% confidence interval
      [CI] [1.02, 1.17]) and with lower 8-week point-prevalence abstinence (odds ratio
      = .91, 95% CI [.86, .97])-relations that remained significant when other
      withdrawal symptoms were included as predictors. Finally, nicotine replacement
      therapy nearly fully suppressed the increase in abstinence-related anhedonia
      (beta = -.66, p < .001), suggesting agonist suppression of withdrawal. Results
      suggest that anhedonia is a unique and motivationally significant element of the
      tobacco withdrawal syndrome in humans. These results have implications for
      defining and assessing tobacco use disorder and for understanding and treating
      tobacco addiction.

PMID- 25384070
TI  - Stability of the DSM-5 Section III pathological personality traits and their
      longitudinal associations with psychosocial functioning in personality disordered
      individuals.
AB  - This study was conducted to establish (a) the stability of the DSM-5 Section III
      personality disorder (PD) traits, (b) whether these traits predict future
      psychosocial functioning, and (c) whether changes in traits track with changes in
      psychosocial functioning across time. Ninety-three outpatients (61% female)
      diagnosed with at least 1 PD completed patient-report measures at 2 time-points
      (M time between assessments = 1.44 years), including the Personality Inventory
      for the DSM-5 and several measures of psychosocial functioning. Effect sizes of
      rank-order and mean-level change were calculated. In addition, Time 1 traits were
      used to predict functioning measures at Time 2. Finally, latent change score
      models were estimated for DSM-5 Section III traits and functioning measures, and
      correlations among latent change scores were calculated to establish the
      relationship between change in traits and functional outcomes. Findings
      demonstrated that the DSM-5 Section III traits were highly stable in terms of
      normative (i.e., mean-level) change and rank-order stability over the course of
      the study. Furthermore, traits prospectively predicted psychosocial functioning.
      However, at the individual level traits and functioning were not entirely static
      over the study, and change in individuals' functioning tracked with changes in
      trait levels. These findings demonstrate that the DSM-5 Section III traits are
      highly stable consistent with the definition of PD, prospectively predictive of
      psychosocial functioning, and are dynamically associated with functioning over
      time. This study provides important evidence in support of the DSM-5 Section III
      PD model.

PMID- 25384071
TI  - Social information embedded in vocalizations induces neurogenomic and behavioral
      responses.
AB  - Social cues facilitate relationships within communities. Zebra finches form long
      term stable mate pairs and produce offspring within a multi-family, multi
      generational community that can include hundreds of birds. Males use song to
      communicate in this complex environment. Males sing as part of their courtship
      display but also abundantly throughout each day, suggesting a role for their
      vocal signature outside of a reproductive context. One advantage of a vocal
      social cue is that it can be exchanged when birds are out of visual contact, as
      regularly occurs in a zebra finch community. Previous works have demonstrated
      that females hearing song are affected by their social relationship to the bird
      singing it, and the immediate social context. Here, we probed the question of
      whether or not the song itself carried social information, as would be expected
      from the situations when males sing outside of view of the female. We quantified
      behavioral and neurogenomic responses to two songs we predicted would have
      distinct "attractive" qualities in adult females housed in either mixed sex or
      female-only social communities. Our results show that only mixed sex-housed
      females show distinctive behavioral and neurogenomic responses to attractive
      songs. These data are consistent with the idea that the acoustic properties of
      song carry social information, and that the current social situation modulates
      the neural and behavioral responses to these signals. 

PMID- 25384073
TI  - Use of disulfiram for alcohol relapse prevention in patients in opioid
      maintenance treatment.
AB  - OBJECTIVES: The aim of this study was to assess the effectiveness, tolerability,
      and safety of alcohol relapse prevention with disulfiram in alcohol-dependent
      patients in opioid maintenance treatment under routine treatment conditions.
      METHODS: Twenty-nine opioid maintenance treatment patients were observed from the
      beginning of outpatient disulfiram treatment for up to 6 months. Patients
      received disulfiram (mostly 300 mg/d) together with their daily opioid dose.
      Patients were assessed through urine screens for alcohol (ethyl gluconoride) and
      other drugs at least twice monthly; blood chemistry analyses after 1, 3, and 6
      months; and clinical interviews after 3 and 6 months. RESULTS: Most patients
      presented with somatic and/or psychiatric comorbidity and/or polydrug use at
      baseline. Half of the patients completed 6 months of disulfiram treatment.
      Alcohol use was low during disulfiram treatment. Levels of other drug use did not
      change. For most patients, 1 or more adverse events were reported, often mild
      and/or short lived. Three patients experienced severe adverse events attributable
      to disulfiram. CONCLUSIONS: Disulfiram is a viable treatment option for the high
      risk population studied here. A close monitoring of side effects and adverse
      events is necessary, in particular, in patients with polysubstance use.

PMID- 25384072
TI  - Expression profiles of PIWIL2 short isoforms differ in testicular germ cell
      tumors of various differentiation subtypes.
AB  - PIWI family proteins have recently emerged as essential contributors in numerous
      biological processes including germ cell development, stem cell maintenance and
      epigenetic reprogramming. Expression of some of the family members has been shown
      to be elevated in tumors. In particular, PIWIL2 has been probed as a potential
      neoplasia biomarker in many cancers in humans. Previously, PIWIL2 was shown to be
      expressed in most tumours as a set of its shorter isoforms. In this work, we
      demonstrated the presence of its 60 kDa (PL2L60A) and 80 kDa (PL2L80A) isoforms
      in testicular cancer cell lines. We also ascertained the transcriptional
      boundaries of mRNAs and alternative promoter regions for these PIWIL2 isoforms.
      Further, we probed a range of testicular germ cell tumor (TGCT) samples and found
      PIWIL2 to be predominantly expressed as PL2L60A in most of them. Importantly, the
      levels of both PL2L60A mRNA and protein products were found to vary depending on
      the differentiation subtype of TGCTs, i.e., PL2L60A expression is significantly
      higher in undifferentiated seminomas and appears to be substantially decreased in
      mixed and nonseminomatous TGCTs. The higher level of PL2L60A expression in
      undifferentiated TGCTs was further validated in the model system of retinoic acid
      induced differentiation in NT2/D1 cell line. Therefore, both PL2L60A mRNA and
      protein abundance could serve as an additional marker distinguishing between
      seminomas and nonseminomatous tumors with different prognosis and therapy
      approaches. 

PMID- 25384074
TI  - Dopamine agonist modifies cortical activity in Parkinson disease: a functional
      neuroimaging study.
AB  - OBJECTIVES: To investigate, using functional magnetic resonance imaging, the
      influence of a long-term dopaminergic therapy on brain activation during a simple
      motor task in early, previously untreated patients with Parkinson disease.
      METHODS: Thirteen patients with Parkinson disease in Hoehn-Yahr stage 1 or 2,
      with a right predominance of the disease, underwent functional magnetic resonance
      imaging during self-paced continuous right-hand tapping before and after 6 months
      of therapy with ropinirole 15 mg/d. The task was monitored online with a
      dedicated device, which measures the strength and frequency of the tapping.
      RESULTS: All patients with Parkinson disease on ropinirole treatment showed a
      clinically significant improvement, and their functional magnetic resonance
      imaging pattern after treatment showed a reduced activation in the right
      postcentral (primary sensory-motor area), supramarginal and inferior parietal
      gyri compared with the activation pattern before treatment. No area of increased
      activation was observed after therapy. CONCLUSIONS: In line with the classical
      functional deafferentation hypothesis, dopaminergic stimulation should increase
      motor cortex activity as a result of restoration of the striatocortical loops. On
      the contrary, our results challenge this hypothesis as we found decreased
      cerebral activity after a short-term chronic dopaminergic treatment. We suggest
      that the recruitment of cortical motor circuits aimed to overcome the functional
      deficit of the striatocortical loops lessens after dopaminergic treatment.

PMID- 25384075
TI  - Antidepressant-emergent mood switch in Korean adolescents with mood disorder.
AB  - OBJECTIVES: The objectives of this study were to compare clinical characteristics
      of children and adolescents who experienced antidepressant-emergent mood switch
      (AEMS) and those who did not, and to investigate the predictors of AEMS in a
      clinical sample of Korean children and adolescents. METHODS: Two psychiatrists
      retrospectively reviewed the medical records of 115 children and adolescents
      (age, 15.0 [2.0] years; 45 boys) that were prescribed antidepressants or
      lamotrigine for the treatment of a depressive episode of bipolar or depressive
      disorders from March 2010 to February 2012 at the Department of Psychiatry of
      Asan Medical Center. The diagnosis was reviewed and confirmed for each subject.
      Demographic information, clinical characteristics, family history, and
      psychiatric comorbidities were compared across subjects with and without AEMS.
      RESULTS: Twelve subjects (10.4%) experienced AEMS. The latency to AEMS was 25.9
      (20.9) days (range, 2-56 days; median, 18 days). Antidepressant-emergent mood
      switch was more frequent in subjects with bipolar disorder (BD) than in subjects
      with depressive disorder (P < 0.001) and in subjects with high socioeconomic
      status (P < 0.001). Previous suicidal attempt (P = 0.001), previous
      antidepressant exposure (P = 0.001), number of previous antidepressant exposures
      (P < 0.001), family history of other psychiatric disorder (P = 0.001), and
      concomitant antipsychotics (P = 0.006) were more common in subjects with AEMS
      than in subjects without AEMS. In multivariate logistic regression, diagnosis of
      BD (odds ratio [95% confidence interval], 15.94 [1.83-139.16]), concomitant
      antipsychotics (26.90 [2.43-297.38]), and family history of other psychiatric
      disorder (39.55 [3.05-512.22]) were significant predictors of AEMS. CONCLUSIONS:
      Children and adolescents who experienced AEMS had distinct profiles of clinical
      characteristics. Antidepressant-emergent mood switch may be more associated with
      BD than with depressive disorder.

PMID- 25384076
TI  - A case of abulia, status/post right middle cerebral artery territory infarct,
      treated successfully with olanzapine.
AB  - Abulia refers to a pathological deficit of willpower. Disruption of frontal
      subcortical-mesolimbic circuits caused by lesions in certain central nervous
      system structures has been associated with abulia. Given the neurobiological link
      between the dopaminergic reward system and the psychological phenomenon of
      motivation, it has been speculated that modulating dopaminergic neurotransmission
      will potentially alter the clinical presentation of abulia. We present a case of
      abulia S/P right middle cerebral artery, treated successfully with olanzapine. 

PMID- 25384078
TI  - Sex differences in the pharmacokinetics of levodopa in elderly patients with
      Parkinson disease.
AB  - OBJECTIVES: Levodopa (LD) is the most effective antiparkinsonian drug used in the
      treatment of Parkinson disease (PD). Sex differences in the bioavailability of LD
      have been shown previously. In addition, epidemiological sex differences in PD
      have been reported, suggesting an involvement of estrogen. In this study, we
      evaluated the pharmacokinetics of LD in elderly patients with PD to examine the
      influence of estrogen. METHODS: After the oral administration of a tablet of LD
      100 mg/carbidopa 10 mg in 128 PD patients (including 91 elderly patients; age at
      examination, 75 years or older), plasma LD concentrations were measured at 6
      points until 180 minutes, and pharmacological parameters were calculated. Then,
      differences in these parameters between sex were compared. RESULTS: The area
      under the curve (AUC) and the AUC adjusted for body weight were found to be
      significantly greater in the female subjects compared with the male subjects (P <
      0.0001 and P < 0.0001, respectively). Furthermore, in the elderly patients, the
      AUC and the AUC adjusted for body weight were significantly greater among the
      female subjects (P < 0.0001 and P < 0.0001, respectively). CONCLUSIONS: Even in
      the elderly cohort, the women had a significantly greater bioavailability of LD.
      In conclusion, to avoid the development of motor complications during LD
      treatment, it is important to consider the sex differences in the bioavailability
      of LD.

PMID- 25384077
TI  - Nocturnal bruxism in a patient with Behcet disease and posttraumatic stress
      disorder successfully treated with gabapentin.
AB  - Bruxism is an involuntary movement, including teeth grinding and clenching, which
      occur primarily during sleep. Although Behcet disease and posttraumatic stress
      disorder both have a high prevalence of sleep problems, bruxism is extremely rare
      in these 2 disorders. Here, we report a rare case of concurrent Behcet disease
      and posttraumatic stress disorder, which presented with antidepressant-refractory
      sleep disturbance accompanied by teeth grinding, clenching, and snoring that was
      successfully treated with gabapentin. 

PMID- 25384079
TI  - Bupropion XL-induced motor and vocal tics.
AB  - Tics are stereotypical repetitive involuntary movements (motor tics) or sounds
      (vocal tics). Although the emergence of tics were reported in a few cases with
      the use of selective serotonin reuptake inhibitors, there was no case with
      bupropion extended-release (Bupropion XL). The current case report presents a
      male patient developing motor and vocal tics with the use of bupropion XL. 

PMID- 25384080
TI  - Labour induction with an intermediate-dose oxytocin regimen has advantages over a
      high-dose regimen.
AB  - A total of 200 women planned for labour induction were randomised to receive high
      dose oxytocin (6 mU/min with similar increments every 45 min) or intermediate
      dose oxytocin (3 mU/min with similar increments every 45 min). Oxytocin solution
      was prepared with 30 units in 500 ml saline with which the infusion rate in ml/h
      is numerically equal to oxytocin in mU/min. We observed that the caesarean rate
      (18% vs 6%, p = 0.009), contraction abnormalities (35% vs 14%, p = 0.0005) and
      neonatal bilirubin levels (7.99 +/- 2.70 vs 6.80 +/- 2.65, p = 0.002) were higher
      with high-dose than with intermediate-dose. The induction-delivery interval (IDI)
      was similar (10 h 13 min with high-dose and 11 h 5 min with intermediate-dose; p
      = 0.237, NS). Nulliparous women benefited more with intermediate-dose as the
      caesarean rate was higher with high-dose (24.6% vs 7.9%, p = 0.011). Although the
      caesarean rate was higher in multiparous women with high-dose oxytocin, it was
      statistically not significant (5.7% vs 2.7%; p = 0.609). Oxytocin regimens for
      labour induction are usually high-dose (4-6 mU/min) or low-dose (1-1.5 mU/min).
      The former is associated with more contraction abnormalities and the latter with
      prolonged IDI; both result in an increased caesarean rate. In order to offset
      these disadvantages, an intermediate- dose regimen was selected. The increment
      interval of 45 min was selected in accordance with the pharmacokinetics of
      oxytocin. We observed a lower caesarean rate when compared with the high-dose
      regimen, without any increase in the IDI. Hence, we propose that the intermediate
      dose oxytocin regimen should be preferred to the high-dose regimen for labour
      induction. 

PMID- 25384081
TI  - Highly-effective gating of single-molecule junctions: an electrochemical
      approach.
AB  - We report an electrochemical gating approach with ~100% efficiency to tune the
      conductance of single-molecule 4,4'-bipyridine junctions using scanning
      tunnelling-microscopy break junction technique. Density functional theory
      calculation suggests that electrochemical gating aligns molecular frontier
      orbitals relative to the electrode Fermi-level, switching the molecule from an
      off resonance state to "partial" resonance. 

PMID- 25384082
TI  - Ab initio structure search and in situ 7Li NMR studies of discharge products in
      the Li-S battery system.
AB  - The high theoretical gravimetric capacity of the Li-S battery system makes it an
      attractive candidate for numerous energy storage applications. In practice, cell
      performance is plagued by low practical capacity and poor cycling. In an effort
      to explore the mechanism of the discharge with the goal of better understanding
      performance, we examine the Li-S phase diagram using computational techniques and
      complement this with an in situ (7)Li NMR study of the cell during discharge.
      Both the computational and experimental studies are consistent with the
      suggestion that the only solid product formed in the cell is Li2S, formed soon
      after cell discharge is initiated. In situ NMR spectroscopy also allows the
      direct observation of soluble Li(+)-species during cell discharge; species that
      are known to be highly detrimental to capacity retention. We suggest that during
      the first discharge plateau, S is reduced to soluble polysulfide species
      concurrently with the formation of a solid component (Li2S) which forms near the
      beginning of the first plateau, in the cell configuration studied here. The NMR
      data suggest that the second plateau is defined by the reduction of the residual
      soluble species to solid product (Li2S). A ternary diagram is presented to
      rationalize the phases observed with NMR during the discharge pathway and provide
      thermodynamic underpinnings for the shape of the discharge profile as a function
      of cell composition. 

PMID- 25384084
TI  - University travel bans and quarantines may impede Ebola response.

PMID- 25384083
TI  - COPD and bronchiectasis: phenotype, endotype or co-morbidity?

PMID- 25384085
TI  - Anchored multiplex PCR for targeted next-generation sequencing.
AB  - We describe a rapid target enrichment method for next-generation sequencing,
      termed anchored multiplex PCR (AMP), that is compatible with low nucleic acid
      input from formalin-fixed paraffin-embedded (FFPE) specimens. AMP is effective in
      detecting gene rearrangements (without prior knowledge of the fusion partners),
      single nucleotide variants, insertions, deletions and copy number changes.
      Validation of a gene rearrangement panel using 319 FFPE samples showed 100%
      sensitivity (95% confidence limit: 96.5-100%) and 100% specificity (95%
      confidence limit: 99.3-100%) compared with reference assays. On the basis of our
      experience with performing AMP on 986 clinical FFPE samples, we show its
      potential as both a robust clinical assay and a powerful discovery tool, which we
      used to identify new therapeutically important gene fusions: ARHGEF2-NTRK1 and
      CHTOP-NTRK1 in glioblastoma, MSN-ROS1, TRIM4-BRAF, VAMP2-NRG1, TPM3-NTRK1 and
      RUFY2-RET in lung cancer, FGFR2-CREB5 in cholangiocarcinoma and PPL-NTRK1 in
      thyroid carcinoma. AMP is a scalable and efficient next-generation sequencing
      target enrichment method for research and clinical applications. 

PMID- 25384086
TI  - Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph
      nodes.
AB  - Antibodies are critical for defense against a variety of microbes, but they may
      also be pathogenic in some autoimmune diseases. Many effector functions of
      antibodies are mediated by Fcgamma receptors (FcgammaRs), which are found on most
      immune cells, including dendritic cells (DCs)-important antigen-presenting cells
      that play a central role in inducing antigen-specific tolerance or immunity.
      Following antigen acquisition in peripheral tissues, DCs migrate to draining
      lymph nodes via the lymphatics to present antigen to T cells. Here we demonstrate
      that FcgammaR engagement by IgG immune complexes (ICs) stimulates DC migration
      from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC
      stimulated mouse and human DCs showed greater directional migration in a
      chemokine (C-C) ligand 19 (CCL19) gradient and increased chemokine (C-C) receptor
      7 (CCR7) expression. Using intravital two-photon microscopy, we observed that
      local administration of IC resulted in dermal DC mobilization. We confirmed that
      dermal DC migration to lymph nodes depended on CCR7 and increased in the absence
      of the inhibitory receptor FcgammaRIIB. These observations have relevance to
      autoimmunity because autoantibody-containing serum from humans with systemic
      lupus erythematosus (SLE) and from a mouse model of SLE also increased dermal DC
      migration in vivo, suggesting that this process may occur in lupus, potentially
      driving the inappropriate localization of autoantigen-bearing DCs. 

PMID- 25384088
TI  - Discovery of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H
      pyrazol-5-yl)pyridazin-4(1H)-one (TAK-063), a highly potent, selective, and
      orally active phosphodiesterase 10A (PDE10A) inhibitor.
AB  - A novel series of pyridazinone-based phosphodiesterase 10A (PDE10A) inhibitors
      were synthesized. Our optimization efforts using structure-based drug design
      (SBDD) techniques on the basis of the X-ray crystal structure of PDE10A in
      complex with hit compound 1 (IC50 = 23 nM; 110-fold selectivity over other PDEs)
      led to the identification of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3
      (1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (27h). Compound 27h has potent
      inhibitory activity (IC50 = 0.30 nM), excellent selectivity (>15000-fold
      selectivity over other PDEs), and favorable pharmacokinetics, including high
      brain penetration, in mice. Oral administration of compound 27h to mice elevated
      striatal 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine
      monophosphate (cGMP) levels at 0.3 mg/kg and showed potent suppression of
      phencyclidine (PCP)-induced hyperlocomotion at a minimum effective dose (MED) of
      0.3 mg/kg. Compound 27h (TAK-063) is currently being evaluated in clinical trials
      for the treatment of schizophrenia. 

PMID- 25384087
TI  - Longitudinal PET-MRI reveals beta-amyloid deposition and rCBF dynamics and
      connects vascular amyloidosis to quantitative loss of perfusion.
AB  - The dynamics of beta-amyloid deposition and related second-order physiological
      effects, such as regional cerebral blood flow (rCBF), are key factors for a
      deeper understanding of Alzheimer's disease (AD). We present longitudinal in vivo
      data on the dynamics of beta-amyloid deposition and the decline of rCBF in two
      different amyloid precursor protein (APP) transgenic mouse models of AD. Using a
      multiparametric positron emission tomography and magnetic resonance imaging
      approach, we demonstrate that in the presence of cerebral beta-amyloid angiopathy
      (CAA), beta-amyloid deposition is accompanied by a decline of rCBF. Loss of
      perfusion correlates with the growth of beta-amyloid plaque burden but is not
      related to the number of CAA-induced microhemorrhages. However, in a mouse model
      of parenchymal beta-amyloidosis and negligible CAA, rCBF is unchanged. Because
      synaptically driven spontaneous network activity is similar in both transgenic
      mouse strains, we conclude that the disease-related decline of rCBF is caused by
      CAA. 

PMID- 25384089
TI  - Increased expression of cathepsin L: a novel independent prognostic marker of
      worse outcome in hepatocellular carcinoma patients.
AB  - OBJECTIVES: To investigate the expression and role of Cathepsin L (CTSL) in
      Hepatocellular carcinoma (HCC) tissue and cell line (MHCC-97H), and to evaluate
      the clinical and prognostic significance of CTSL protein in patients with HCC.
      METHODS: The expression of CTSL was examined in HCC tissue and MHCC-97H cells by
      Western-blotting, Real-time PCR and immunohistochemical staining. Cell growth
      curve assay and colony formation assay were used to verify the effect of CTSL on
      the proliferation and tumor progression ability of MHCC-97H cells. Tumor
      formation assay in nude mice was used to analyze the effect of CTSL on the
      tumorigenicity of MHCC-97H cells. RESULTS: The status of CTSL protein in
      carcinoma tissues is much higher than that in paracarcinoma tissues. The overall
      survival of the patients with high CTSL expression was significantly shorter than
      the low CTSL expression group. high CTSL expression was significantly correlated
      with advanced clinical staging, histological grade and tumor recurrence. In vitro
      experiments demonstrated that over-expression of CTSL in MHCC-97H cells promoted
      cell proliferation and tumor progression ability. Down-regulation of CTSL showed
      the opposite effects. Over-expression of CTSL increase the tumorigenicity of MHCC
      97H cells by in vivo experiments. Moreover, multivariate analysis suggested that
      CTSL expression might be an independent prognostic indicator for the survival of
      HCC patients after curative surgery. CONCLUSIONS: CTSL might involve in the
      development and progression of HCC as a oncogene, and thereby may be a valuable
      prognostic marker for HCC patients.

PMID- 25384090
TI  - Lipoic acid and bone marrow derived cells therapy induce angiogenesis and cell
      proliferation after focal brain injury.
AB  - Abstract Introduction: Traumatic brain injury is a main cause of disability and
      death in developed countries, above all among children and adolescents. The
      intrinsic inability of the central nervous system to efficiently repair traumatic
      injuries renders transplantation of bone marrow-derived cells (BMDC) a promising
      approach towards repair of brain lesions. On the other hand, many studies have
      reported the beneficial effect of Lipoic acid (LA), a potent antioxidant
      promoting cell survival, angiogenesis and neuroregeneration. METHODS: In this
      study, the cortex of adult mice was cryo-injured in order to mimic local
      traumatic brain injury. Vehicle or freshly prepared BMDC were grafted in the
      cerebral penumbra area 24 hours after unilateral local injury alone or combined
      with intra-peritoneal LA administration as a new regenerative strategy. RESULTS:
      Differences were found in the process of cell proliferation, angiogenesis and
      glial scar formation after local injury depending of the applied treatment,
      either LA or BMDC alone or in combination. CONCLUSION: The data presented here
      suggest that transplantation of BMDC is a good alternative and valid strategy to
      treat a focal brain injury when LA could not be prescribed due to its non-desired
      secondary effects.

PMID- 25384091
TI  - Self-immolative phthalate esters sensitive to hydrogen peroxide and light.
AB  - Self-immolative aryl phthalate esters were conjugated with cleavable masking
      groups sensitive to light and hydrogen peroxide. The phthalate linker releases
      the fluorescent dye 7-hydroxycoumarin upon exposure to light or H2O2,
      respectively, leading to an increase in fluorescence. The light-sensitive aryl
      phthalate ester is demonstrated as a pro-fluorophore in cultured S2 cells. 

PMID- 25384092
TI  - Feeding tube placement in patients with advanced cancer: a teachable moment.

PMID- 25384093
TI  - Reading grade level and completeness of freely available materials on thyroid
      nodules: there is work to be done.
AB  - BACKGROUND: Patient education is one of the key components required for patients
      to participate in decision making for their care. Sources of information should
      be complete and understandable. The objective of this study was to assess the
      quality and reading grade level of freely available materials pertaining to the
      evaluation and treatment of thyroid nodules. METHODS: All available materials
      were gathered through a comprehensive Internet search or direct contact with each
      identified organization associated with thyroid care. Materials meeting inclusion
      criteria were assessed for completeness of content and reading grade level using
      the SMOG readability formula. Then, the DISCERN instrument was utilized to assess
      the quality of the five materials which had the best (lowest) and the five
      materials that had the worst (highest) SMOG reading grade levels. RESULTS: A
      total of 63 materials on thyroid nodule evaluation and management were
      identified. A minority of materials presented readers with a complete picture of
      the topic, describing both benefits and cautions of thyroid nodule evaluation,
      benefits and cautions of fine-needle thyroid nodule biopsy, or risks, benefits,
      and long-term effects of thyroidectomy. The SMOG reading grade level assessment
      was well above recommended levels. The range was eighth grade to college level;
      the mean and median reading grade level were 13. Lastly, the DISCERN instrument
      revealed that most of the materials with both the best and the worst reading
      grade levels assessed had "extensive or serious shortcomings" that would impede
      their usefulness as high-quality sources of information regarding management
      options. CONCLUSIONS: Existing thyroid nodule evaluation and management materials
      have serious shortcomings. Future work should focus on the development of patient
      materials that are both grade level appropriate and meet the DISCERN criteria for
      topic completeness and accuracy.

PMID- 25384094
TI  - Resolubilization of precipitated intact membrane proteins with cold formic acid
      for analysis by mass spectrometry.
AB  - Protein precipitation in organic solvent is an effective strategy to deplete
      sodium dodecyl sulfate (SDS) ahead of MS analysis. Here we evaluate the recovery
      of membrane and water-soluble proteins through precipitation with
      chloroform/methanol/water or with acetone (80%). With each solvent system,
      membrane protein recovery was greater than 90%, which was generally higher than
      that of cytosolic proteins. With few exceptions, residual supernatant proteins
      detected by MS were also detected in the precipitation pellet, having higher MS
      signal intensity in the pellet fraction. Following precipitation, we present a
      novel strategy for the quantitative resolubilization of proteins in an MS
      compatible solvent system. The pellet is incubated at -20  degrees C in 80%
      formic acid/water and then diluted 10-fold with water. Membrane protein recovery
      matches that of sonication of the pellet in 1% SDS. The resolubilized proteins
      are stable at room temperature, with no observed formylation as is typical of
      proteins suspended in formic acid at room temperature. The protocol is applied to
      the molecular weight determination of membrane proteins from a GELFrEE
      fractionated sample of Escherichia coli proteins. 

PMID- 25384098
TI  - Relationships Between Questionnaire Ratings of Sleep Quality and Polysomnography
      in Healthy Adults.
AB  - This study aimed to examine the association between polysomnographic sleep and
      subjective habitual sleep quality and restoration from sleep. Thirty-one normal
      sleepers completed the Karolinska Sleep Questionnaire and multiple home
      polysomnography recordings (n = 2-5). Using linear regression, sleep quality and
      restoration were separately analyzed as functions of standard polysomnography
      parameters: sleep efficiency, total sleep time, sleep latency, stage 1 and 2
      sleep, slow-wave sleep, rapid eye movement sleep, wake time after sleep onset,
      and awakenings (n), averaged across recordings. Stage 2 and slow-wave sleep
      predicted worse and better sleep quality, respectively. Also, slow-wave sleep
      predicted less subjective restoration, although adjustment for age attenuated
      this relation. Our findings lend some physiological validity to ratings of
      habitual sleep quality in normal sleepers. Data were less supportive of a
      physiological correlate of ratings of restoration from sleep. 

PMID- 25384100
TI  - Silas Weir Mitchell on epilepsy therapy in the late 19th to early 20th centuries.
AB  - Silas Weir Mitchell (1829-1914), one of the fathers of American neurology, is
      well known for many contributions to neurology. However, his efforts in epilepsy
      are overshadowed by his other accomplishments. Mitchell introduced a new bromide
      preparation, lithium bromide, as a viable therapy. His most widely accepted
      contribution to the field was the introduction of inhaled amyl nitrite for early
      termination of seizures accompanied by an appropriate aura. Despite the prevalent
      views on lifestyle modification as a treatment for epilepsy during this time
      period, as well as Mitchell's own development of the "rest cure" for certain
      disease states, he was not a proponent of these types of interventions for
      epilepsy, nor did he support interventions focused on other organ systems, such
      as abdominal or gynecologic surgery. Mitchell had distinct opinions on the
      treatment of epilepsy, and helped to advance its therapeutics during his career. 

PMID- 25384101
TI  - [Test your knowledge].

PMID- 25384102
TI  - [Diagnosis of pulmonary hypertension - novelties after the 5th world conference].

PMID- 25384099
TI  - Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum
      disorders.
AB  - IMPORTANCE: Short transverse myelitis (STM; <3 vertebral segments) is considered
      noncharacteristic of neuromyelitis optica (NMO) spectrum disorders (NMOSDs).
      Nonappreciation of the potential for STM to occur in NMOSD may lead to increased
      disability from delay in diagnosis and appropriate treatment. OBJECTIVES: To
      determine the frequency of short lesions at the initial myelitis manifestation of
      NMOSD and to compare the demographic, clinical, and radiological characteristics
      of aquaporin-4-IgG (AQP4-IgG) seropositive and seronegative STM. DESIGN, SETTING,
      AND PARTICIPANTS: We reviewed the records and images of patients at the Mayo
      Clinic who were identified as AQP4-IgG positive from 1996 to 2014. Inclusion
      criteria were first STM episode, magnetic resonance imaging performed 90 days or
      less from symptom onset, spinal cord T2-hyperintense lesion less than 3 vertebral
      segments, AQP4-IgG seropositivity, and a final diagnosis of NMO or NMOSD.
      Patients with an initial longitudinally extensive transverse myelitis were
      excluded (n = 151). Patients with STM who were seronegative for AQP4-IgG among an
      Olmsted County population-based cohort of inflammatory demyelinating disorders of
      the central nervous system were used as a control group. MAIN OUTCOMES AND
      MEASURES: Delay to diagnosis in months, clinical and radiological
      characteristics, and disability measured by ambulatory status. RESULTS: Twenty
      five patients who were AQP4-IgG seropositive with an initial STM represented 14%
      of initial myelitis episodes among patients with NMOSD. The STM episode was
      defined as the first manifestation of NMOSD in 10 patients (40%) preceded by
      optic neuritis in 13 patients (52%) and preceded by a nausea and vomiting episode
      in 2 patients (8%). In comparison with the excluded patients with NMOSD who had
      an initial longitudinally extensive transverse myelitis, delay to
      diagnosis/treatment was greater when initial lesions were short (P = .02). In
      AQP4-IgG-positive STM cases, subsequent myelitis episodes were longitudinally
      extensive in 92%. Attributes more common in patients with AQP4-IgG-positive STM
      than in 27 population-based patients with AQP4-IgG-negative STM included the
      following: nonwhite race/ethnicity; tonic spasms; coexisting autoimmunity;
      magnetic resonance imaging (central cord lesions, T1 hypointensity, and a brain
      inconsistent with multiple sclerosis); and cerebrospinal fluid (oligoclonal bands
      lacking). CONCLUSIONS AND RELEVANCE: Short transverse myelitis is not uncommon in
      NMOSD and, when it is present, delays diagnosis and treatment. Clinical and
      radiological characteristics identified in this study may help select patients
      with STM who are at the highest risk for an NMOSD. Short transverse myelitis does
      not exclude consideration of AQP4-IgG testing or NMOSD diagnosis.

PMID- 25384103
TI  - [Thomas Mann's account of his lung operation].

PMID- 25384105
TI  - Efficacy of rhBMP-2 loaded PCL/PLGA/beta-TCP guided bone regeneration membrane
      fabricated by 3D printing technology for reconstruction of calvaria defects in
      rabbit.
AB  - We successfully fabricated a three-dimensional (3D) printing-based PCL/PLGA/beta
      TCP guided bone regeneration (GBR) membrane that slowly released rhBMP-2. To
      impregnate the GBR membrane with intact rhBMP-2, collagen solution encapsulating
      rhBMP-2 (5 ug ml(-1)) was infused into pores of a PCL/PLGA/beta-TCP membrane
      constructed using a 3D printing system with four dispensing heads. In a release
      profile test, sustained release of rhBMP-2 was observed for up to 28 d. To
      investigate the efficacy of the GBR membrane on bone regeneration, PCL/PLGA/beta
      TCP membranes with or without rhBMP-2 were implanted in an 8 mm calvaria defect
      of rabbits. Bone formation was evaluated at weeks 4 and 8 histologically and
      histomorphometrically. A space making ability of the GBR membrane was
      successfully maintained in both groups, and significantly more new bone was
      formed at post-implantation weeks 4 and 8 by rhBMP-2 loaded GBR membranes.
      Interestingly, implantation with rhBMP-2 loaded GBR membranes led to almost
      entire healing of calvaria defects within 8 weeks.

PMID- 25384106
TI  - Staphylococcal food poisoning case and molecular analysis of toxin genes in
      Staphylococcus aureus strains isolated from food in Sicily, Italy.
AB  - A case of staphylococcal food poisoning was observed in two individuals of the
      same family after consumption of primosale, a semiripened sheep cheese produced
      in Sicily. Staphylococcus aureus isolated from the cheese produced enterotoxin C
      (SEC) and carried both the enterotoxin C (sec) and the toxic shock syndrome toxin
      (tsst-1) gene. Following this case, an extensive survey was conducted on 971 food
      samples (raw milk, cheese, meat, and food preparations). S. aureus was detected
      in 102 of 971 food samples, from all types of food with the exception of ricotta
      cheese. The tsst-1 gene was present in 42% of the strains, either alone or in
      combination with other toxin genes. The enterotoxin C gene was the most
      represented enterotoxin, but it was only found in dairy products. Six S. aureus
      isolates carried the sea gene alone, two isolates carried both sea and seb, and
      one isolate carried both sea and sec. A significant percentage (46%) of all
      isolates carried a toxin gene, creating significant concern that virulent S.
      aureus can be transmitted through food in Sicily. 

PMID- 25384107
TI  - Rapid analysis of deoxynivalenol in durum wheat by FT-NIR spectroscopy.
AB  - Fourier-transform-near infrared (FT-NIR) spectroscopy has been used to develop
      quantitative and classification models for the prediction of deoxynivalenol (DON)
      levels in durum wheat samples. Partial least-squares (PLS) regression analysis
      was used to determine DON in wheat samples in the range of <50-16,000 ug/kg DON.
      The model displayed a large root mean square error of prediction value (1,977
      ug/kg) as compared to the EU maximum limit for DON in unprocessed durum wheat
      (i.e., 1,750 ug/kg), thus making the PLS approach unsuitable for quantitative
      prediction of DON in durum wheat. Linear discriminant analysis (LDA) was
      successfully used to differentiate wheat samples based on their DON content. A
      first approach used LDA to group wheat samples into three classes: A (DON <=
      1,000 ug/kg), B (1,000 < DON <= 2,500 ug/kg), and C (DON > 2,500 ug/kg) (LDA I).
      A second approach was used to discriminate highly contaminated wheat samples
      based on three different cut-off limits, namely 1,000 (LDA II), 1,200 (LDA III)
      and 1,400 ug/kg DON (LDA IV). The overall classification and false compliant
      rates for the three models were 75%-90% and 3%-7%, respectively, with model LDA
      IV using a cut-off of 1,400 ug/kg fulfilling the requirement of the European
      official guidelines for screening methods. These findings confirmed the
      suitability of FT-NIR to screen a large number of wheat samples for DON
      contamination and to verify the compliance with EU regulation. 

PMID- 25384109
TI  - A new method for peptide synthesis in the N->C direction: amide assembly through
      silver-promoted reaction of thioamides.
AB  - The Ag(I)-promoted coupling of amino acids and peptides with amino ester
      thioamides generates peptide imides without epimerisation. The peptide imides
      undergo regioselective hydrolysis under mild conditions to generate native
      peptides. This method was employed to prepare the pentapeptide thymopentin in the
      N->C direction, in high yield and purity.

PMID- 25384108
TI  - Molecular and insecticidal characterization of a novel Cry-related protein from
      Bacillus thuringiensis toxic against Myzus persicae.
AB  - This study describes the insecticidal activity of a novel Bacillus thuringiensis
      Cry-related protein with a deduced 799 amino acid sequence (~89 kDa) and ~19%
      pairwise identity to the 95-kDa-aphidicidal protein (sequence number 204) from
      patent US 8318900 and ~40% pairwise identity to the cancer cell killing Cry
      proteins (parasporins Cry41Ab1 and Cry41Aa1), respectively. This novel Cry
      related protein contained the five conserved amino acid blocks and the three
      conserved domains commonly found in 3-domain Cry proteins. The protein exhibited
      toxic activity against the green peach aphid, Myzus persicae (Sulzer) (Homoptera:
      Aphididae) with the lowest mean lethal concentration (LC50 = 32.7 MUg/mL)
      reported to date for a given Cry protein and this insect species, whereas it had
      no lethal toxicity against the Lepidoptera of the family Noctuidae Helicoverpa
      armigera (Hubner), Mamestra brassicae (L.), Spodoptera exigua (Hubner), S.
      frugiperda (J.E. Smith) and S. littoralis (Boisduval), at concentrations as high
      as ~3.5 MUg/cm2. This novel Cry-related protein may become a promising
      environmentally friendly tool for the biological control of M. persicae and
      possibly also for other sap sucking insect pests.

PMID- 25384110
TI  - Self-assembled plasmonic nanoparticles on vertically aligned carbon nanotube
      electrodes via thermal evaporation.
AB  - This study details the development of a large-area, three-dimensional (3D),
      plasmonic integrated electrode (PIE) system. Vertically aligned multiwalled
      carbon nanotube (VA-MWNT) electrodes are grown and populated with self-assembling
      silver nanoparticles via thermal evaporation. Due to the geometric and surface
      characteristics of VA-MWNTs, evaporated silver atoms form nanoparticles
      approximately 15-20 nm in diameter. The nanoparticles are well distributed on VA
      MWNTs, with a 5-10 nm gap between particles. The size and gap of the self
      assembled plasmonic nanoparticles is dependent upon both the length of the MWNT
      and the thickness of the evaporated silver. The wetting properties of water of
      the VA-MWNT electrodes change from hydrophilic (~70 degrees ) to hydrophobic
      (~120 degrees ) as a result of the evaporated silver. This effect is particularly
      pronounced on the VA-MWNT electrodes with a length of 1 MUm, where the contact
      angle is altered from an initial 8 degrees  to 124 degrees . Based on UV-visible
      spectroscopic analysis, plasmonic resonance of the PIE systems occurs at a
      wavelength of approximately 400 nm. The optical behavior was found to vary as a
      function of MWNT length, with the exception of MWNT with a length of 1 MUm. Using
      our PIE systems, we were able to obtain clear surface-enhanced Raman scattering
      (SERS) spectra with a detection limit of ~10 nM and an enhancement factor of
      ~10(6). This PIE system shows promise for use as a novel electrode system in next
      generation optoelectronics such as photovoltaics, light-emitting diodes, and
      solar water splitting. 

PMID- 25384111
TI  - Reassessment of the cardio-respiratory stress response, using the king penguin as
      a model.
AB  - Research in to short-term cardio-respiratory changes in animals in reaction to a
      psychological stressor typically describes increases in rate of oxygen
      consumption (V(O2)) and heart rate. Consequently, the broad consensus is that
      they represent a fundamental stressor response generalizable across adult
      species. However, movement levels can also change in the presence of a stressor,
      yet studies have not accounted for this possible confound on heart rate. Thus the
      direct effects of psychological stressors on the cardio-respiratory system are
      not resolved. We used an innovative experimental design employing accelerometers
      attached to king penguins (Aptenodytes patagonicus) to measure and thus account
      for movement levels in a sedentary yet free-to-move animal model during a
      repeated measures stress experiment. As with previous studies on other species,
      incubating king penguins (N = 6) exhibited significant increases in both V(O2)
      and heart rate when exposed to the stressor. However, movement levels, while
      still low, also increased in response to the stressor. Once this was accounted
      for by comparing periods of time during the control and stress conditions when
      movement levels were similar as recorded by the accelerometers, only V(O2)
      significantly increased; there was no change in heart rate. These findings offer
      evidence that changing movement levels have an important effect on the measured
      stress response and that the cardio-respiratory response per se to a
      psychological stressor (i.e. the response as a result of physiological changes
      directly attributable to the stressor) is an increase in V(O2) without an
      increase in heart rate.

PMID- 25384112
TI  - Highly efficient activation of organosilanes with eta2-aldehyde nickel complexes:
      key for catalytic syntheses of aryl-, vinyl-, and alkynyl-benzoxasiloles.
AB  - An eta(2)-aldehyde nickel complex was utilized as an effective activator for an
      organosilane in order to generate a hypervalent silicate reactant for the first
      time. This method was successfully applied to the highly efficient syntheses of 3
      aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles from benzaldehydes with aryl-,
      vinyl-, and alkynylsilyl groups at the ortho position. Initial mechanistic
      studies revealed that an intermolecular aryl transfer process was involved in the
      reaction mechanism. The formation of an eta(2)-aldehyde complex was directly
      confirmed by NMR. 

PMID- 25384113
TI  - A dual FRET based fluorescent probe as a multiple logic system.
AB  - A new fluorescent probe with a unique sequential dual FRET process was designed
      and constructed. This probe showed distinguished responses towards Fe(3+) and
      Hg(2+), making it an ideal candidate for multiple logic operations at the
      molecular level. 

PMID- 25384114
TI  - BaMn9(II)(VO4)6(OH)2: a homospin ferrimagnet with a broken spinel-lattice of B
      sites.
AB  - A new vanadate of BaMn9(II)(VO4)6(OH)2 was synthesized by a conventional
      hydrothermal method. BaMn9(II)(VO4)6(OH)2 crystallizes in the cubic space group
      Pa3[combining macron], which exhibits an edge-sharing MnO6 octahedral network
      structure with cavities occupied by Ba(VO4)6(16-) groups. The lattice built by
      Mn(2+) ions shows the reverse triangular dipyramid Mn7 in the system, which can
      be considered as a broken spin lattice of B-sites in spinels. The title compound
      shows a ferrimagnetic behavior with TC = 18 K. 

PMID- 25384115
TI  - The impact of training sequence and between-category similarity on unsupervised
      induction.
AB  - Studies of supervised categorization often show better learning when examples are
      presented in random alternation rather than massed by category, but such
      interleaving impairs learning in unsupervised tasks. The exemplar comparison
      hypothesis explains this result by assuming that people in unsupervised tasks
      discover generalizations about categories by comparing individual examples, and
      that interleaving increases the difficulty of such within-category comparisons.
      The category invention hypothesis explains the interleaving effect by assuming
      that people are more likely to merge or aggregate potentially separable
      categories when they are interleaved, and this initial failure to recognize
      separate categories then acts as an effective barrier to further learning. The
      present experiments show that the interleaving effect depends on the similarity
      or alignability of the presented categories. This result provides evidence in
      favour of the category invention hypothesis, which expects that highly dissimilar
      (nonalignable) categories will resist aggregation and hence will not be affected
      by interleaving. The nonmonotonic pattern of learning, and the interaction
      between sequence and similarity, observed in the alignable conditions of
      Experiment 3 were also consistent with category invention, but not with exemplar
      comparison. Implications are discussed for real-world learning, especially the
      relationship between exposure and learning and between supervised and
      unsupervised learning. 

PMID- 25384116
TI  - Lavender-thymol as a new topical aromatherapy preparation for episiotomy: A
      randomised clinical trial.
AB  - The objective of this study was to evaluate the effectiveness of topical lavender
      thymol in promoting episiotomy healing. This placebo-controlled, single-blinded,
      randomised clinical trial involved 60 primiparous women. REEDA score was used to
      evaluate the outcome of the trial. On the 7th post-partum day, women in Placebo
      treated group had worse Redness, Edema, Ecchymosis, Discharge and Approximation
      (REEDA) score of 3.93 +/- 3.65 compared with those in Lavender-thymol-treated
      group (2.03 +/- 1.7) with significant difference (P = 0.013). Visual analogue
      Scale (VAS) score for pain at episiotomy in Lavender-thymol-treated group was 3.5
      +/- 1.9, whereas in Placebo-treated group it was 2.1 +/- 2.2 (p = 0.011) for
      dyschezia, 3.8 +/- 1.7 and 2.8 +/- 1.6 in Placebo- and Lavender-thymol-treated
      women, respectively (p = 0.023). At 7th post-partum week, dyspareunia was more
      severe in Placebo-treated group compared with that in Lavender-thymol-treated
      group (5.3 +/- 2.7 vs 2.7 +/- 1.5 and p < 0.001). Topical aromatherapy using
      lavender-thymol was highly effective, suitable and safe for episiotomy wound care
      with little or no expected side effects compared with that using placebo. 

PMID- 25384117
TI  - Increased levetiracetam clearance and breakthrough seizure in a pregnant patient
      successfully handled by intensive therapeutic drug monitoring.
AB  - We report a 36-year-old pregnant patient with subtherapeutic trough plasma levels
      of levetiracetam (LVT) and a breakthrough nocturnal seizure while assuming 3
      times a day dosing of the drug. An intensive pharmacokinetic study was performed
      from immediately before to 11 hours after the morning LVT dose administration and
      suggested that the patient was not adequately exposed to the drug during the
      night. After changing the dosing of LVT to 4 times a day, the patient experienced
      no seizures and delivered a healthy newborn without complications. Afterward,
      trough plasma levels of LVT remained always within the therapeutic range until
      delivery, and no major increase of the drug daily dose was required. 

PMID- 25384118
TI  - Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity
      Disorder Treated With OROS Formulation.
AB  - BACKGROUND: There are limited studies investigating the relationship between oral
      release osmotic system-methylphenidate (OROS-MPH) doses and plasma
      methylphenidate (MPH) concentrations in children and adolescents. The aim of this
      study was to investigate the relationship between the doses of OROS-MPH and the
      plasma levels of the drug. We also examined the effects of the other drugs
      including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of
      the MPH in the plasma. METHODS: The files of 100 attention deficit hyperactivity
      disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD
      according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth
      Edition criteria, were screened. The ages of subjects were between 6 and 18 years
      (mean = 11.5 +/- 3.8 years). Plasma MPH levels were determined by high
      performance liquid chromatography-tandem mass spectrometry assay. RESULTS: Daily
      mean OROS-MPH dose used in ADHD children was 0.7 +/- 0.2 mg/kg (range: 0.3-1.3
      mg/kg). The mean plasma OROS-MPH was 11.6 +/- 7.3 ng/mL (range: 0.5-43.4 ng/mL).
      There was no group difference in the mean plasma MPH and dose-related MPH levels
      between the groups that used any additional drug including aripiprazole (n = 25),
      risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use
      these drugs (P > 0.05). There was a positive correlation between the OROS-MPH
      doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001).
      The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the
      subjects. CONCLUSIONS: Our findings point to the fact that plasma levels of MPH
      show a wide range of changes at similar doses, correlate positively with the
      doses and, as expected, are not affected by using risperidone, sertraline,
      fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize
      MPH dose in patients not responding to treatment or in those experiencing serious
      side effects, but not in routine clinical practice. The presence of intermediate
      dose formulations such as 45-mg tablets for OROS-MPH may contribute to the
      optimization.

PMID- 25384119
TI  - Therapeutic drug monitoring for patients with Alzheimer dementia to improve
      treatment with donepezil.
AB  - BACKGROUND: Aiming to verify that therapeutic drug monitoring has the potential
      to optimize treatment with acetylcholine esterase inhibitors of patients with
      Alzheimer dementia, this study investigated whether serum concentrations of
      donepezil are associated with clinical improvement. METHODS: Clinical improvement
      was measured using the clinical global impression (CGI) scale, and donepezil
      concentrations were measured in serum by a high-performance liquid
      chromatographic method with spectrophotometric detection. RESULTS: In total, 206
      serum samples from 106 patients (49.5% female) were retrospectively available for
      analysis. Patients included were treated under everyday conditions. Their mean +/
      SD age was 72 +/- 9 years, daily doses of donepezil were 5 and 10 mg, and their
      mean +/- SD serum concentrations were 23 +/- 9 and 47 +/- 18 ng/mL, respectively.
      Serum concentrations correlated significantly (P < 0.001) with CGI scores
      (Pearson's correlation coefficient r = 0.511, P < 0.01). In patients who were
      "very much improved," according to their CGI score, the mean serum concentration
      was 66 +/- 20 ng/mL and thus significantly higher (P < 0.01) than in patients
      with "minimal improvement" (29 +/- 12 ng/mL). Receiver operating characteristics
      analysis suggests that donepezil serum concentrations of at least 50 ng/mL may be
      recommended for maximal clinical benefit. CONCLUSIONS: Because donepezil serum
      concentrations were highly variable between individual patients and the majority
      of patients exhibited concentrations that were below 50 ng/mL at therapeutic
      doses of 5 and 10 mg/d, it can be concluded that therapeutic drug monitoring may
      be used to enhance the effectiveness of donepezil treatment.

PMID- 25384120
TI  - Unexpected overestimation of methotrexate plasma concentrations: importance of
      the assay implementation and its validation.

PMID- 25384121
TI  - Acute immune thrombocytopenic purpura following oral polio vaccination.

PMID- 25384122
TI  - Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell
      lung cancer.
AB  - Stathmin 1 (STMN1), a major microtubule-depolymerizing protein, is involved in
      cell cycle progression and cell motility. However, the clinical significance of
      STMN1 expression in non-small cell lung cancer (NSCLC) has not been determined.
      The expression pattern of STMN1 mRNA was analyzed by quantitative real-time PCR
      (qRT-PCR) in 37 cases of NSCLC and in the corresponding non-tumor tissue samples.
      Furthermore, immunohistochemistry was performed to detect STMN1 protein
      expression in 113 primary NSCLC tissues. The functional role of STMN1 in lung
      cancer cell lines was evaluated by small interfering RNA-mediated depletion
      followed by analyses of cell proliferation and invasion. We found that the STMN1
      mRNA and protein levels in NSCLC tissues were significantly higher than those in
      the corresponding non-tumor tissues (P<0.001). In addition, increased STMN1
      expression was correlated with poor tumor differentiation (P<0.001), large tumor
      size (P=0.022), advanced N stage (P=0.033), and advanced TNM stage (P<0.001).
      Kaplan-Meier analysis indicates that NSCLC patients with higher STMN1 expression
      showed significantly worse survival. Moreover, multivariate analysis indicates
      that higher STMN1 protein expression was an independent prognostic factor of
      disease-specific survival (HR 2.247, 95%CI 1.320-3.825, P=0.003). Finally, the
      knockdown of STMN1 in lung cancer cells resulted in a decrease in cellular
      proliferation and invasion. Our findings suggest that STMN1 may have an important
      role in NSCLC progression and could serve as a potential prognostic marker for
      patients with NSCLC. 

PMID- 25384123
TI  - Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial
      inflammation and fibrosis in a rat model of polymyositis.
AB  - Cathepsin B (CB) is involved in the turnover of proteins and has various roles in
      maintaining the normal metabolism of cells. In our recent study, CB is increased
      in the muscles of polymyositis/dermatomyositis (PM/DM). However, the role of CB
      in interstitial lung disease (ILD) has not been reported. ILD is a frequent
      complication of PM/DM, which is the leading cause of death in PM/DM. It carries
      high morbidity and mortality in connective tissue diseases, characterized by an
      overproduction of inflammatory cytokines and induced fibrosis, resulting in
      respiratory failure. The etiology and pathogenesis of ILD remain incompletely
      understood. This study investigated whether treatment with CA-074Me, a specific
      inhibitor of CB, attenuates ILD in PM. CB expression, inflammation, and fibrosis
      were analyzed in the lung tissues from patients with PM/DM. The animal model of
      PM was induced in guinea pigs with Coxsackie virus B1 (CVB1). CA-074Me was given
      24 h after CVB1 injection for 7 consecutive days. At the end of the experiment,
      the animals were killed and lung tissues were collected for the following
      analysis. Inflammation, fibrosis and apoptosis cells, and cytokines were assessed
      by histological examinations and immunohistochemical analyses, western blot
      analysis and transferase-mediated dUTP nick-end labeling assay. In patients with
      PM/DM, the protein levels of CB were significantly elevated in lung tissues
      compared with healthy controls, which correlated with increases in inflammation
      and fibrosis. Similarly, the expression of CB, inflammation and fibrosis, CD8(+)
      T cell, CD68(+) cell, tumor necrosis factor-alpha, transforming growth factor
      beta1 infiltrations, and apoptotic cell death were significantly increased in
      lung tissues of the guinea-pig model of CVB1-induced PM. These changes were
      attenuated by the administration of CA-074Me. In conclusion, this study
      demonstrates that PM/DM increases CB expression in lung tissues and inhibition of
      CB reduces ILD in a guinea-pig model of CVB1-induced PM. This finding suggests
      that CB may be a potential therapeutic target for ILD. 

PMID- 25384124
TI  - Development of non-traumatic osteonecrosis of the femoral head requires toll-like
      receptor 7 and 9 stimulations and is boosted by repression on nuclear factor
      kappa B in rats.
AB  - Non-traumatic osteonecrosis of the femoral head (ONFH) often occurs after
      corticosteroid therapy in patients with inflammatory diseases. Recent studies
      suggest that toll-like receptor (TLR) signaling may contribute to the
      pathogenesis of inflammatory diseases, and that the reason for corticosteroid
      therapy for inflammatory diseases is related to the anti-inflammatory activities
      of corticosteroids through the reduction of NF-kappaB. We hypothesized that the
      administration of TLR ligands in combination with corticosteroid causes ONFH and
      that transcription factors may contribute to the pathogenesis of ONFH. The aim of
      the study was to evaluate (1) the incidence of ONFH in rats after the
      administration of TLR7 or TLR9 ligands together with methylprednisolone (MPSL)
      and (2) whether transcription factors contribute to the development of ONFH. Male
      Wistar rats (n=148) were divided into five groups as follows: Group 1:
      Saline+MPSL, Group 2: Imiquimod+Saline, Group 3: Imiquimod+MPSL, Group 4: CpG
      C+MPSL, Group 5: Imiquimod+BAY11-7082+MPSL. As a result, ONFH was observed in 0
      of 12 rats in Group 1, in 1 of 10 in Group 2, in 6 of 12 in Group 3, in 4 of 12
      in Group 4, in 0 of 9 in Group 5. MPSL treatment did not significantly affect
      IRF7 activity, whereas NF-kappaB activity was significantly repressed in Group 2
      and Group 3. Furthermore, the repression in interferon regulatory factor 7 (IRF7)
      activity by BAY11-7082 interfered with the development of ONFH simultaneously
      with the MPSL treatment-induced repression in NF-kappaB activity. In conclusion,
      in the present study, corticosteroid treatment after the administration of TLR7
      or TLR9 ligands caused ONFH. Repression in NF-kappaB activity by corticosteroid
      treatment boosted the development of ONFH. 

PMID- 25384125
TI  - Improvement of memory impairments in poststroke patients by hyperbaric oxygen
      therapy.
AB  - OBJECTIVE: Several recent studies have shown that hyperbaric oxygen (HBO2)
      therapy carry cognitive and motor therapeutic effects for patients with acquired
      brain injuries. The goal of this study was to address the specific effects of
      HBO2 on memory impairments after stroke at late chronic stages. METHOD: A
      retrospective analysis was conducted on data of 91 stroke patients 18 years or
      older (mean age ~60 years) who had either ischemic or hemorrhagic stroke 3-180
      months before HBO2 therapy (M = 30-35 months). The HBO2 protocol included 40 to
      60 daily sessions, 5 days per week, 90 min each, 100% oxygen at 2ATA, and memory
      tests were administered before and after HBO2 therapy using NeuroTrax's
      computerized testing battery. Assessments were based on verbal or nonverbal,
      immediate or delayed memory measures. The cognitive tests were compared with
      changes in the brain metabolic state measured by single-photon emission computed
      tomography. RESULTS: Results revealed statistically significant improvements (p <
      .0005, effect sizes medium to large) in all memory measures after HBO2
      treatments. The clinical improvements were well correlated with improvement in
      brain metabolism, mainly in temporal areas. CONCLUSIONS: Although further
      research is needed, the results illustrate the potential of HBO2 for improving
      memory impairments in poststroke patients, even years after the acute event.

PMID- 25384126
TI  - Quality assurance of stereotactic alignment and patient positioning mechanical
      accuracy for robotized Gamma Knife radiosurgery.
AB  - The automatic patient positioning system and its alignment is critical and
      specified to be less than 0.35 mm for a radiosurgical treatment with the latest
      robotized Gamma Knife Perfexion (GKPFX). In this study, we developed a
      quantitative QA procedure to verify the accuracy and robustness of such a system.
      In particular, we applied the test to a unit that has performed >1000 procedures
      at our institution. For the test, a radiochromic film was first placed inside a
      spherical film phantom and then irradiated with a sequence of linearly placed
      shots of equal collimator size (e.g. 4 mm) via the Leksell Gamma Knife Perfexion
      system (PFX). The shots were positioned with either equal or unequal gaps of
      approximately 8 mm both at center and off-center positions of the patient
      positioning system. Two independent methods of localizing the irradiation shot
      center coordinates were employed to measure the gap spacing between adjacent
      shots. The measured distance was then compared with the initial preset values for
      the test. On average, the positioning uncertainty for the PFX delivery system was
      found to be 0.03 +/- 0.2 mm (2sigma). No significant difference in the
      positioning uncertainty was noted among measurements in the x-, y- and z-axis
      orientations. In conclusion, a simple, fast, and quantitative test was developed
      and demonstrated for routine QA of the submillimeter PFX patient positioning
      system. This test also enables independent verification of any patient-specific
      shot positioning for a critical treatment such as a tumor in the brainstem.

PMID- 25384128
TI  - Chemoselective per-O-trimethylsilylation and homogeneous N-functionalisation of
      amino sugars.
AB  - A highly efficient CH3CN-promoted hexamethyldisilazane per-O-trimethylsilylation
      of amino sugars was developed. Its applications in homogenous N-functionalisation
      and a concise synthesis of glucosamine 6-phosphate are described. 

PMID- 25384127
TI  - A case study of magnetic resonance imaging of cerebrovascular reactivity: a
      powerful imaging marker for mild traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To use breath-hold functional magnetic resonance imaging
      (fMRI) to localize the brain regions with impaired cerebrovascular reactivity
      (CVR) in a female patient diagnosed with mild traumatic brain injury (mTBI). The
      extent of impaired CVR was evaluated 2 months after concussion. Follow-up scan
      was performed 1 year post-mTBI using the same breath-hold fMRI technique.
      RESEARCH DESIGN: Case report. METHODS AND PROCEDURES: fMRI blood oxygenation
      dependent level (BOLD) signals were measured under breath-hold challenge in a
      female mTBI patient 2 months after concussion followed by a second fMRI with
      breath-hold challenge 1 year later. CVR was expressed as the percentage change of
      BOLD signals per unit time of breath-hold. MAIN OUTCOMES: In comparison with CVR
      measurement of normal control subjects, statistical maps of CVR revealed
      substantial neurovascular deficits and hemispheric asymmetry within grey and
      white matter in the initial breath-hold fMRI scan. Follow-up breath-hold fMRI
      performed 1 year post-mTBI demonstrated normalization of CVR accompanied with
      symptomatic recovery. CONCLUSIONS: CVR may serve as an imaging biomarker to
      detect subtle deficits in both grey and white matter for individual diagnosis of
      mTBI. The findings encourage further investigation of hypercapnic fMRI as a
      diagnostic tool for mTBI.

PMID- 25384129
TI  - Amyloid-beta-activated human microglial cells through ER-resident proteins.
AB  - Microglial activation in the central nervous system is a key event in the
      neuroinflammation that accompanies neurodegenerative diseases such as Alzheimer's
      disease (AD). Among cytokines involved in microglial activation, amyloid beta
      (Abeta) peptide is known to be a key molecule in the induction of diverse
      inflammatory products, which may lead to chronic inflammation in AD. However,
      proteomic studies of microglia in AD are limited due to lack of proper cell or
      animal model systems. In this study, we performed a proteomic analysis of Abeta
      stimulated human microglial cells using SILAC (stable isotope labeling with amino
      acids in cell culture) combined with LC-MS/MS. Results showed that 60 proteins
      increased or decreased their abundance by 1.5 fold or greater. Among these, ER
      resident proteins such as SERPINH1, PDIA6, PDIA3, and PPIB were revealed to be
      key molecular biomarkers of human microglial activation by validation of the
      proteomic results by immunostaining, PCR, ELISA, and Western blot. Taken
      together, our data suggest that ER proteins play an essential role in human
      microglial activation by Abeta and may be important molecular therapeutic targets
      for treatment of AD. 

PMID- 25384130
TI  - Computational tool for risk assessment of nanomaterials: novel QSTR-perturbation
      model for simultaneous prediction of ecotoxicity and cytotoxicity of uncoated and
      coated nanoparticles under multiple experimental conditions.
AB  - Nanomaterials have revolutionized modern science and technology due to their
      multiple applications in engineering, physics, chemistry, and biomedicine.
      Nevertheless, the use and manipulation of nanoparticles (NPs) can bring serious
      damages to living organisms and their ecosystems. For this reason, ecotoxicity
      and cytotoxicity assays are of special interest in order to determine the
      potential harmful effects of NPs. Processes based on ecotoxicity and cytotoxicity
      tests can significantly consume time and financial resources. In this sense,
      alternative approaches such as quantitative structure-activity/toxicity
      relationships (QSAR/QSTR) modeling have provided important insights for the
      better understanding of the biological behavior of NPs that may be responsible
      for causing toxicity. Until now, QSAR/QSTR models have predicted ecotoxicity or
      cytotoxicity separately against only one organism (bioindicator species or cell
      line) and have not reported information regarding the quantitative influence of
      characteristics other than composition or size. In this work, we developed a
      unified QSTR-perturbation model to simultaneously probe ecotoxicity and
      cytotoxicity of NPs under different experimental conditions, including diverse
      measures of toxicities, multiple biological targets, compositions, sizes and
      conditions to measure those sizes, shapes, times during which the biological
      targets were exposed to NPs, and coating agents. The model was created from 36488
      cases (NP-NP pairs) and exhibited accuracies higher than 98% in both training and
      prediction sets. The model was used to predict toxicities of several NPs that
      were not included in the original data set. The results of the predictions
      suggest that the present QSTR-perturbation model can be employed as a highly
      promising tool for the fast and efficient assessment of ecotoxicity and
      cytotoxicity of NPs. 

PMID- 25384131
TI  - Water-soluble colorimetric and ratiometric fluorescent probe for selective
      imaging of palladium species in living cells.
AB  - A novel water-soluble colorimetric and ratiometric fluorescent probe was
      synthesized and applied to imaging palladium species under physiological
      conditions in phosphate buffered saline (PBS) containing less than 1% organic
      cosolvent without adding any additional reagents. Based on palladium triggered
      terminal propargyl ethers cleavage reaction, the probe exhibited a high
      selectivity and sensitivity for palladium species of all the typical oxidation
      states (0, +2, +4), with a low detection limit (25 nM, 2.7 MUg/L) and an obvious
      color change. Furthermore, the probe was successfully used for ratiometric
      fluorescence imaging of palladium in living cells. 

PMID- 25384132
TI  - From germ cell preservation to regenerative medicine: an exciting research career
      in biotechnology.
AB  - Collection, manipulation, assessment, and storage of mammalian gametes, embryos,
      and stem cells are providing important opportunities in agriculture, research,
      and medicine. Semen and embryo freezing in livestock are used in breeding
      schemes, especially in cattle and for international trade, with no risk of
      spreading disease. In human medicine, they are used in treatment of infertility.
      Usually, knowledge gained in one species is applicable in the others. In one
      exception, some ruminant embryos cultured according to protocols used in human in
      vitro fertilization become unusually large offspring. This is due to disturbances
      in expression of imprinted genes. The nuclear transfer procedure developed at the
      Roslin Institute is being used to make genetic modifications in livestock to
      either direct production of biomedical proteins, create animal models of human
      disease, or enhance animal health and productivity. Human pluripotent cells are
      being used in Edinburgh to identify drugs to treat degenerative diseases. 

PMID- 25384133
TI  - Genomic imprinting in farm animals.
AB  - The mouse is the first species in which genomic imprinting was studied.
      Imprinting research in farm species has lagged behind owing to a lack of
      sequencing and genetic background information, as well as long generation
      intervals and high costs in tissue collection. Since the creation of Dolly, the
      first cloned mammal from an adult sheep, studies on genomic imprinting in
      domestic species have accelerated because animals from cloning and other assisted
      reproductive technologies exhibit phenotypes of imprinting disruptions. Although
      this review focuses on new developments in farm animals, most of the imprinting
      mechanism information was derived from the mouse.

PMID- 25384134
TI  - Recent advances in primate phylogenomics.
AB  - The world of primate genomics is expanding rapidly in new and exciting ways owing
      to lowered costs and new technologies in molecular methods and bioinformatics.
      The primate order is composed of 78 genera and 478 species, including human.
      Taxonomic inferences are complex and likely a consequence of ongoing
      hybridization, introgression, and reticulate evolution among closely related
      taxa. Recently, we applied large-scale sequencing methods and extensive taxon
      sampling to generate a highly resolved phylogeny that affirms, reforms, and
      extends previous depictions of primate speciation. The next stage of research
      uses this phylogeny as a foundation for investigating genome content, structure,
      and evolution across primates. Ongoing and future applications of a robust
      primate phylogeny are discussed, highlighting advancements in adaptive evolution
      of genes and genomes, taxonomy and conservation management of endangered species,
      next-generation genomic technologies, and biomedicine.

PMID- 25384135
TI  - Domestication genomics: evidence from animals.
AB  - Animal domestication has far-reaching significance for human society. The
      sequenced genomes of domesticated animals provide critical resources for
      understanding the genetic basis of domestication. Various genomic analyses have
      shed a new light on the mechanism of artificial selection and have allowed the
      mapping of genes involved in important domestication traits. Here, we summarize
      the published genomes of domesticated animals that have been generated over the
      past decade, as well as their origins, from a phylogenomic point of view. This
      review provides a general description of the genomic features encountered under a
      two-stage domestication process. We also introduce recent findings for
      domestication traits based on results from genome-wide association studies and
      selective-sweep scans for artificially selected genomic regions. Particular
      attention is paid to issues relating to the costs of domestication and the
      convergent evolution of genes between domesticated animals and humans.

PMID- 25384136
TI  - Behavior genetics and the domestication of animals.
AB  - Across species, a similar suite of traits tends to develop in response to
      domestication, including modifications in behavior. Reduced fear and increased
      stress tolerance were central in early domestication, and many domestication
      related behaviors may have developed as traits correlated to reduced fear.
      Genetic mechanisms involved in domestication of behavior can be investigated by
      using top-down or bottom-up approaches, either starting from the behavior
      variation and searching for underlying genes or finding selected loci and then
      attempting to identify the associated phenotypes. Combinations of these
      approaches have proven powerful, and examples of results from such studies are
      presented and discussed. This includes loci associated with tameness in foxes and
      dogs, as well as loci correlated with reduced aggression and increased sociality
      in chickens. Finally, some examples are provided on epigenetic mechanisms in
      behavior, and it is suggested that selection of favorable epigenetic variants may
      have been an important mechanism in domestication.

PMID- 25384137
TI  - Applied animal genomics: results from the field.
AB  - Genomic selection (GS) is the use of statistical methods to estimate the genetic
      merit of a genotyped animal based on prediction equations derived from large
      ancestral populations with both phenotypes and genotypes. It has revolutionized
      the dairy cattle breeding industry and has been implemented with varying degrees
      of success in other animal breeding programs, including swine, poultry, and beef
      cattle. The findings of empirical field studies applying GS to the breeding
      sectors of these main animal protein industries are reviewed. Several
      translational considerations must be addressed before implementing GS in genetic
      improvement programs. These include determining and obtaining economically
      relevant phenotypes and determining the optimal size of the training population,
      cost-effective genotyping strategies, the practicality of field implementation,
      and the relative costs versus the benefits of the realized rate of genetic gain.
      GS may additionally change the optimal breeding scheme design, and studies that
      address this consideration are also reviewed briefly.

PMID- 25384138
TI  - Pestiviruses.
AB  - Pestiviruses cause economically important diseases among domestic ruminants and
      pigs, but they may also infect a wide spectrum of wild species of even-toed
      ungulates (Artiodactyla). Bovine viral diarrhea virus (BVDV) and Border disease
      virus of sheep infect their hosts either transiently or persistently. Cellular
      and humoral immunotolerance to the infecting strain is a unique feature of
      persistent infection (PI) by ruminant pestiviruses. Persistence, caused by
      transplacental infection early in fetal development, depends on virally encoded
      interferon antagonists that inactivate the host's innate immune response to the
      virus without globally interfering with its function against other viruses. At
      epidemiological equilibrium, approximately 1-2% of animals are PI. Successful
      BVDV control programs show that removal of PI animals results in viral extinction
      in the host population. The nucleotide sequences of ruminant pestiviruses change
      little during persistent infection. Nevertheless, they display large
      heterogeneity, pointing to a long history of virus-host coevolution in which
      avirulent strains are more successful.

PMID- 25384139
TI  - Pathogenesis and molecular biology of a transmissible tumor in the Tasmanian
      devil.
AB  - The emergence of a fatal transmissible cancer known as devil facial tumor disease
      (DFTD) is threatening the iconic Tasmanian devil with extinction in the wild
      within the next few decades. Since the first report of the disease in 1996, DFTD
      has spread to over 85% of the devils' distribution and dramatically reduced devil
      numbers. Research into DFTD has focused on gaining a deeper understanding of the
      disease on multiple levels, including an accurate assessment of the tissue origin
      of the tumor, elucidation of how the tumor evades immune detection, and
      determination of how the tumor is transmitted between individuals and how it is
      evolving as it spreads through the population. Knowledge gained from these
      studies has important implications for DFTD management and devil conservation.

PMID- 25384140
TI  - Animal models of bovine leukemia virus and human T-lymphotrophic virus type-1:
      insights in transmission and pathogenesis.
AB  - Bovine leukemia virus (BLV) and human T-lymphotrophic virus type-1 (HTLV-1) are
      related retroviruses associated with persistent and lifelong infections and a low
      incidence of lymphomas within their hosts. Both viruses can be spread through
      contact with bodily fluids containing infected cells, most often from mother to
      offspring through breast milk. Each of these complex retroviruses contains
      typical gag, pol, and env genes but also unique, nonstructural proteins encoded
      from the pX region. These nonstructural genes encode the Tax and Rex regulatory
      proteins, as well as novel proteins essential for viral spread in vivo.
      Improvements in the molecular tools to test these viral determinants in cellular
      and animal models have provided new insights into the pathogenesis of each virus.
      Comparisons of BLV and HTLV-1 provide insights into mechanisms of spread and
      tumor formation, as well as potential approaches to therapeutic intervention
      against the infections.

PMID- 25384141
TI  - Malignant catarrhal fever: inching toward understanding.
AB  - Malignant catarrhal fever (MCF) is an often lethal infection of many species in
      the order Artiodactyla. It is caused by members of the MCF virus group within
      Gammaherpesvirinae. MCF is a worldwide problem and has a significant economic
      impact on highly disease-susceptible hosts, such as cattle, bison, and deer.
      Several epidemiologic forms of MCF, defined by the reservoir ruminant species
      from which the causative virus arises, are recognized. Wildebeest-associated MCF
      (WA-MCF) and sheep-associated MCF (SA-MCF) are the most prevalent and well
      studied forms of the disease. Historical understanding of MCF is largely based on
      WA-MCF, in which the causative virus can be propagated in vitro. Characterization
      of SA-MCF has been constrained because the causative agent has never been
      successfully propagated in vitro. Development of molecular tools has enabled more
      definitive studies on SA-MCF. The current understanding of MCF, including its
      etiological agents, epidemiology, pathogenesis, and prevention, is the subject of
      the present review.

PMID- 25384142
TI  - Comparative immune systems in animals.
AB  - Animal immune systems can be classified into those of innate immunity and those
      of adaptive immunity. It is generally thought that the former are universal for
      all animals and depend on germline-encoded receptors that recognize highly
      conserved pathogen-associated molecular patterns (PAMPs), whereas the latter are
      vertebrate specific and are mediated primarily by lymphocytes bearing a unique
      antigen receptor. However, novel adaptive or adaptive-like immunities have been
      found in invertebrates and jawless vertebrates, and extraordinarily complex
      innate immunities, created through huge expansions of many innate gene families,
      have recently been found in the cephalochordate amphioxus and the echinoderm sea
      urchin. These studies not only inspire immunologists to seek novel immune
      mechanisms in invertebrates but also raise questions about the origin and
      evolution of vertebrate immunities.

PMID- 25384143
TI  - Origin and evolution of adaptive immunity.
AB  - The evolutionary emergence of vertebrates was accompanied by major morphological
      and functional innovations, including the development of an adaptive immune
      system. Vertebrate adaptive immunity is based on the clonal expression of
      somatically diversifying antigen receptors on lymphocytes. This is a common
      feature of both the jawless and jawed vertebrates , although these two groups of
      extant vertebrates employ structurally different types of antigen receptors and
      principal mechanisms for their somatic diversification . These observations
      suggest that the common vertebrate ancestor must have already possessed a complex
      immune system, including B- and T-like lymphocyte lineages and primary lymphoid
      organs, such as the thymus, but possibly lacked the facilities for somatic
      diversification of antigen receptors. Interestingly, memory formation, previously
      considered to be a defining feature of adaptive immunity, also occurs in the
      context of innate immune responses and can even be observed in unicellular
      organisms, attesting to the convergent evolutionary history of distinct aspects
      of adaptive immunity.

PMID- 25384144
TI  - The functional significance of cattle major histocompatibility complex class I
      genetic diversity.
AB  - Current concerns about food security highlight the importance of maintaining
      productive and disease-resistant livestock populations. Major histocompatibility
      complex (MHC) class I genes have a central role in immunity. A high level of
      diversity in these genes allows populations to survive despite exposure to
      rapidly evolving pathogens. This review aims to describe the key features of MHC
      class I genetic diversity in cattle and to discuss their role in disease
      resistance. Discussion centers on data derived from the cattle genome sequence
      and studies addressing MHC class I gene expression and function. The impact of
      intensive selection on MHC diversity is also considered. A high level of
      complexity in MHC class I genes and functionally related gene families is
      revealed. This highlights the need for increased efforts to determine key genetic
      components that govern cattle immune responses to disease, which is increasingly
      important in the face of changing human and environmental demands.

PMID- 25384145
TI  - Incidence of abnormal offspring from cloning and other assisted reproductive
      technologies.
AB  - In animals produced by assisted reproductive technologies, two abnormal
      phenotypes have been characterized. Large offspring syndrome (LOS) occurs in
      offspring derived from in vitro cultured embryos, and the abnormal clone
      phenotype includes placental and fetal changes. LOS is readily apparent in
      ruminants, where a large calf or lamb derived from in vitro embryo production or
      cloning may weigh up to twice the expected body weight. The incidence of LOS
      varies widely between species. When similar embryo culture conditions are applied
      to nonruminant species, LOS either is not as dramatic or may even be unapparent.
      Coculture with serum and somatic cells was identified in the 1990s as a risk
      factor for abnormal development of ruminant pregnancies. Animals cloned from
      somatic cells may display a combination of fetal and placental abnormalities that
      are manifested at different stages of pregnancy and postnatally. In highly
      interventional technologies, such as nuclear transfer (cloning), the incidence of
      abnormal offspring continues to be a limiting factor to broader application of
      the technique. This review details the breadth of phenotypes found in nonviable
      pregnancies, together with the phenotypes of animals that survive the transition
      to extrauterine life. The focus is on animals produced using in vitro embryo
      culture and nuclear transfer in comparison to naturally occurring phenotypes.

PMID- 25384146
TI  - Preadipocyte and adipose tissue differentiation in meat animals: influence of
      species and anatomical location.
AB  - Early in porcine adipose tissue development, the stromal-vascular (SV) elements
      control and dictate the extent of adipogenesis in a depot-dependent manner. The
      vasculature and collagen matrix differentiate before overt adipocyte
      differentiation. In the fetal pig, subcutaneous (SQ) layer development is
      predictive of adipocyte development, as the outer, middle, and inner layers of
      dorsal SQ adipose tissue develop and maintain layered morphology throughout
      postnatal growth of SQ adipose tissue. Bovine and ovine fetuses contain brown
      adipose tissue but SQ white adipose tissue is poorly developed structurally.
      Fetal adipose tissue differentiation is associated with the precocious expression
      of several genes encoding secreted factors and key transcription factors like
      peroxisome proliferator activated receptor (PPAR)gamma and CCAAT/-enhancer
      binding protein. Identification of adipocyte-associated genes differentially
      expressed by age, depot, and species in vivo and in vitro has been achieved using
      single-gene analysis, microarrays, suppressive subtraction hybridization, and
      next-generation sequencing applications. Gene polymorphisms in PPARgamma,
      cathepsins, and uncoupling protein 3 have been associated with back fat
      accumulation. Genome scans have mapped several quantitative trait loci (QTL)
      predictive of adipose tissue-deposition phenotypes in cattle and pigs.

PMID- 25384147
TI  - Serotonin: a local regulator in the mammary gland epithelium.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a very simple molecule that plays key
      roles in complex communication mechanisms within the animal body. In the mammary
      glands, serotonin biosynthesis and secretion are induced in response to dilation
      of the alveolar spaces. Since its discovery several years ago, mammary 5-HT has
      been demonstrated to perform two homeostatic functions. First, serotonin
      regulates lactation and initiates the transition into the earliest phases of
      involution. Second, serotonin is a local signal that induces parathyroid hormone
      related peptide (PTHrP), which allows the mammary gland to drive the mobilization
      of calcium from the skeleton. These processes use different receptor types, 5-HT7
      and 5-HT2, respectively. In this review, we provide synthetic perspectives on the
      fundamental processes of lactation homeostasis and the adaptation of calcium
      homeostasis for lactation. We analyze the role of the intrinsic serotonin system
      in the physiological regulation of the mammary glands. We also consider the
      importance of the mammary serotonin system in pathologies and therapies
      associated with lactation and breast cancer.

PMID- 25384148
TI  - Evolution of the modern broiler and feed efficiency.
AB  - Although the chicken was domesticated during the Neolithic period, the
      development of the modern broiler is a recent event that has occurred within the
      past 100 years. The chicken's adaptability has allowed it to be grown globally
      under a range of husbandry conditions. That is, the same genetic stock may be
      found in a range of environments, where it is noted for rapid growth to market
      weight and efficiency of feed use, which has increased dramatically, mainly
      through genetic selection. Under good husbandry and a high-energy diet, at 35
      days of age a 1.40-kg broiler required 3.22 kg of feed in 1985. Twenty-five years
      later, we have a 2.44-kg broiler produced on 3.66 kg of feed. This review
      attempts to address the history of factors contributing to these changes,
      obstacles that have had to be overcome, and future limitations.

PMID- 25384149
TI  - Amino acid nutrition in animals: protein synthesis and beyond.
AB  - Amino acids (AA) have enormous physiological importance, serving as building
      blocks for proteins and substrates for synthesis of low-molecular-weight
      substances. Based on growth or nitrogen balance, AA were traditionally classified
      as nutritionally essential or nonessential for animals. Although those AA that
      are not synthesized in eukaryotes (nutritionally essential AA, EAA) must be
      present in animal diets, nutritionally nonessential AA (NEAA) have long been
      ignored for all species. Emerging evidence shows that nonruminants cannot
      adequately synthesize NEAA or conditionally essential AA (CEAA) to realize their
      growth or anti-infection potential. Likewise, all preformed AA are needed for
      high-producing cows and rapidly growing ruminants. Many NEAA and CEAA (e.g.,
      arginine, glutamine, glutamate, glycine, and proline) and certain EAA (e.g.,
      leucine and tryptophan) participate in cell signaling, gene expression, and
      metabolic regulation. Thus, functions of AA beyond protein synthesis must be
      considered in dietary formulations to improve efficiency of nutrient use, growth,
      development, reproduction, lactation, and well-being in animals.

PMID- 25384150
TI  - The suckling piglet as an agrimedical model for the study of pediatric nutrition
      and metabolism.
AB  - The neonatal pig ranks among the most prominent research models for the study of
      pediatric nutrition and metabolism. Its precocial development at birth affords
      ready adaptation to artificial rearing systems, and research using this model
      spans a wide array of nutrients. Sophisticated in vitro and in vivo methodologies
      supporting both invasive, reduction-science research as well as whole-animal
      preclinical investigations have been developed. Potential applications may dually
      benefit both agricultural and medical sciences (e.g., "agrimedical research").
      The broad scope of this review is to outline the fundamental elements of the
      piglet model and to highlight key aspects of relevance to various macronutrients,
      including lipids, carbohydrates, proteins/amino acids, and calcium/phosphorus.
      The review examines similarities between piglets and infants and also piglet
      idiosyncrasies, concluding that, overall, the piglet represents an adaptable and
      robust model for pediatric nutrition and metabolism research.

PMID- 25384151
TI  - Cattle production systems: Ecology of existing and emerging Escherichia coli
      types related to foodborne illness.
AB  - Shiga toxin-producing Escherichia coli (STEC), particularly STEC O157, cause rare
      but potentially serious human infections. Infection with STEC occurs by fecal
      oral transmission, most commonly through food. Cattle are the most important
      reservoir for human STEC exposure, and efforts to control the flow of STEC
      through beef processing have reduced rates of human illness. However, further
      reduction in human incidence of STEC may require control of the pathogen in
      cattle populations. The ecology of STEC in cattle production systems is complex
      and explained by factors that favor (a) colonization in the gut, (b) survival in
      the environment, and (c) ingestion by another cattle host. Although nature
      creates seasonal environmental conditions that do not favor STEC transmission in
      cattle, human efforts to control STEC by environmental manipulation have not
      succeeded. Vaccines and direct-fed microbial products have reduced the carriage
      of STEC by cattle, and other interventions are under investigation.

PMID- 25384152
TI  - Gastrointestinal tract microbiota and probiotics in production animals.
AB  - The gastrointestinal tract (GIT) microbiomes of production animals are now firmly
      established as a key feature underscoring animal health, development, and
      productivity. In particular, early gut colonization is critically important to
      the morphological and immunological development of the GIT, development of a
      functional fermentative environment, and neonatal resistance to pathogenic
      challenge. Although perturbations of an animal's GIT microbiome at any age can
      have profound consequences, perturbations during early GIT development can be
      particularly severe and result in significant and long-lasting sequelae. As the
      GIT microbiome matures, it exhibits significant diversity, ostensibly an
      important indicator of ecosystem health. Recognition of the immense importance of
      the GIT microbiota to the host has led to the development of probiotic and
      prebiotic feedstuffs with the express aim of ensuring animal health. We herein
      review the current collective understanding of the GIT microbiota of production
      animals.

PMID- 25384153
TI  - Biodiversity of cone snails and other venomous marine gastropods: evolutionary
      success through neuropharmacology.
AB  - Venomous marine snails (superfamily Conoidea) are a remarkably biodiverse marine
      invertebrate lineage (featuring more than 10,000 species). Conoideans use complex
      venoms (up to 100 different components for each species) to capture prey and for
      other biotic interactions. Molecular phylogeny and venom peptide characterization
      provide an unusual multidisciplinary view of conoidean biodiversity at several
      taxonomic levels. Venom peptides diverge between species at an unprecedented rate
      through hypermutation within gene families. Clade divergence within a genus
      occurs without recruiting new gene families when a saltatory event, such as
      colonization of new prey types (e.g., fish), leads to a new radiation. Divergence
      between genera in the same family involves substantial divergence in gene
      families. In the superfamily Conoidea, the family groups recruited distinct sets
      of different venom gene superfamilies. The associated morphological, behavioral,
      and prey-preference changes that accompany these molecular changes are unknown
      for most conoidean lineages, except for one genus, Conus, for which many
      associated phenotypic changes have been documented.

PMID- 25384154
TI  - Ecological risk analysis and genetically modified salmon: management in the face
      of uncertainty.
AB  - The commercialization of growth hormone transgenic Atlantic salmon for
      aquaculture has become a controversial public policy issue. Concerns exist over
      the potential ecological effects of this biotechnology should animals escape
      captivity. From within an ecological risk-analysis framework, science has been
      sought to provide decision makers with evidence upon which to base regulatory
      decisions pertaining to genetically modified salmon. Here I review the available
      empirical information on the potential ecological and genetic effects of
      transgenic salmon and discuss the underlying eco-evolutionary science behind the
      topic. I conclude that data gaps and irreducible epistemic uncertainties limit
      the role of scientific inference in support of ecological risk management for
      transgenic salmon. I argue that predictive uncertainties are pervasive in complex
      eco-evolutionary systems and that it behooves those involved in the risk-analysis
      process to accept and communicate these limitations in the interest of timely,
      clear, and cautious risk-management options.

PMID- 25384155
TI  - The modern feedlot for finishing cattle.
AB  - The modern beef feedlot has evolved into a complex system that is very dependent
      upon technology. Modern feedlots are organized into departments, often including
      the office, cattle, yard, feed milling, and feed departments, that allow for
      improvements in production efficiency through the specialization of management
      and labor. Regardless of size, feedlots must succeed at the following tasks:
      cattle procurement, cattle receiving, cattle processing, daily cattle
      observations, health treatments, cattle marketing, feed procurement, feed
      commodity receiving, feed commodity storage, diet formulation, diet delivery,
      bunk management, and environmental management. Apart from cattle ownership,
      feedlots create most of their gross income from feed sales, yardage, inventory
      gain on flaked grain, and combinations of these sources. The future of the
      industry is filled with economic and political challenges, including high grain
      prices owing to competition from the ethanol industry, environmental regulations,
      excess feedlot capacity, and a diminishing labor pool owing to declining rural
      populations.

PMID- 25384156
TI  - The nexus of environmental quality and livestock welfare.
AB  - In recent years, the livestock production industry has been receiving pressure to
      assess and improve production practices in two seemingly unrelated areas:
      environmental quality and animal welfare. In this article, we argue that the
      nexus of these two areas of study should be a priority for future research and
      that the integration of these disciplines in research, extension, and education
      efforts has the potential to improve the sustainability of production livestock
      agriculture.

PMID- 25384158
TI  - The relative function of damaged kidneys in children does not deteriorate further
      at 3-year follow-up.
AB  - PURPOSE: It is thought that the function of a damaged kidney will deteriorate
      further with time because of impaired maturation and compensatory
      hyperfiltration. The aim of this study was to determine changes in relative renal
      function (RRF) over time in children with vesicoureteric reflux (VUR) and/or
      urinary tract infection (UTI) where the unilaterally scarred kidney was found to
      contribute 30% or less to overall function. PATIENTS AND METHODS: Children who
      met the inclusion criteria and had multiple radionuclide studies during a 12-year
      period were identified, and RRF was compared. RESULTS: Twenty-seven boys and 3
      girls with a median age of 0.8 years (0.08-13.05 years) were included. Eight
      patients had unilateral VUR, 21 patients had bilateral VUR, and 1 patient had
      UTIs without VUR. Twenty-one patients underwent reimplantation surgery, and 9
      were managed conservatively.At a mean follow-up of 2.64 years (0.26-6.77 years),
      there was a nonsignificant mean decrease in RRF from 19% (11%-28%) to 18% (9%
      29%). The mean change in renal function was not affected by the severity of the
      initial RRF. CONCLUSIONS: In the medium term, there is no deterioration of RRF of
      unilaterally severely damaged kidneys associated with either VUR or UTI managed
      either surgically or conservatively. Boys are at a much greater risk of severe
      reflux nephropathy.

PMID- 25384157
TI  - Discovery of AM-7209, a potent and selective 4-amidobenzoic acid inhibitor of the
      MDM2-p53 interaction.
AB  - Structure-based rational design and extensive structure-activity relationship
      studies led to the discovery of AMG 232 (1), a potent piperidinone inhibitor of
      the MDM2-p53 association, which is currently being evaluated in human clinical
      trials for the treatment of cancer. Further modifications of 1, including
      replacing the carboxylic acid with a 4-amidobenzoic acid, afforded AM-7209 (25),
      featuring improved potency (KD from ITC competition was 38 pM, SJSA-1 EdU IC50 =
      1.6 nM), remarkable pharmacokinetic properties, and in vivo antitumor activity in
      both the SJSA-1 osteosarcoma xenograft model (ED50 = 2.6 mg/kg QD) and the HCT
      116 colorectal carcinoma xenograft model (ED50 = 10 mg/kg QD). In addition, 25
      possesses distinct mechanisms of elimination compared to 1. 

PMID- 25384159
TI  - Scrotal peritoneal mesothelioma on PET/CT.
AB  - Although malignant mesothelioma originating from the tunica vaginalis has been
      reported in the literature, direct invasion of malignant peritoneal mesothelioma
      to the scrotal cavity has not been described yet. Herein, we presented a diffuse
      malignant peritoneal mesothelioma extending inferiorly to the scrotum via
      inguinal canal detected on FDG PET/CT. 

PMID- 25384160
TI  - Protecting-group-free total synthesis of aplykurodinone-1.
AB  - A concise, stereoselective, and protecting-group-free total synthesis of
      aplykurodinone-1 from Hajos-Parrish ketone was described. The synthetic approach
      features a sequence of aerobic allylic oxidation and elimination of alcohol 9.
      The key intermediate for this synthesis was formed by a stereoselective
      intramolecular radical cyclization. 

PMID- 25384161
TI  - Piperine inhibits platelet-derived growth factor-BB-induced proliferation and
      migration in vascular smooth muscle cells.
AB  - The proliferation and migration of vascular smooth muscle cells (VSMCs) in blood
      vessels are important in the pathogenesis of vascular disorders such as
      atherosclerosis and restenosis. Piperine, a major component of black pepper, has
      antioxidant, anticancer, and anti-inflammatory activity. However, the
      antiatherosclerotic effects of piperine have not been investigated. In this
      study, the effects of piperine on platelet-derived growth factor (PDGF)-BB
      induced proliferation and migration of VSMCs were investigated. The
      antiproliferative effects of piperine were determined using MTT assays, cell
      counting, real-time polymerase chain reaction, and western blots. Our results
      showed that piperine significantly attenuated the proliferation of VSMCs by
      increasing the expression of p27(kip1), regulating the mRNA expression of cell
      cycle enzymes (cyclin D, cyclin E, and PCNA), and decreasing the phosphorylation
      of extracellular signal-regulated kinase (ERK)1/2 in a noncytotoxic concentration
      dependent manner (30-100 MUM). Moreover, we examined the effects of piperine on
      the migration of PDGF-BB-stimulated VSMCs, as determined by the Boyden chamber
      assay, H2DCFDA staining, and western blots. Our results showed that 100 MUM
      piperine decreased cell migration, the production of reactive oxygen species
      (ROS), and phosphorylation of the p38 mitogen-activated protein kinase (MAPK).
      Taken together, our results suggest that piperine inhibits PDGF-BB-induced
      proliferation and the migration of VSMCs by inducing cell cycle arrest and
      suppressing MAPK phosphorylation and ROS. These findings suggest that piperine
      may be beneficial for the treatment of vascular-related disorders and diseases. 

PMID- 25384162
TI  - Conceptual structure and the procedural affordances of rational numbers:
      relational reasoning with fractions and decimals.
AB  - The standard number system includes several distinct types of notations, which
      differ conceptually and afford different procedures. Among notations for rational
      numbers, the bipartite format of fractions (a/b) enables them to represent 2
      dimensional relations between sets of discrete (i.e., countable) elements (e.g.,
      red marbles/all marbles). In contrast, the format of decimals is inherently 1
      dimensional, expressing a continuous-valued magnitude (i.e., proportion) but not
      a 2-dimensional relation between sets of countable elements. Experiment 1 showed
      that college students indeed view these 2-number notations as conceptually
      distinct. In a task that did not involve mathematical calculations, participants
      showed a strong preference to represent partitioned displays of discrete objects
      with fractions and partitioned displays of continuous masses with decimals.
      Experiment 2 provided evidence that people are better able to identify and
      evaluate ratio relationships using fractions than decimals, especially for
      discrete (or discretized) quantities. Experiments 3 and 4 found a similar pattern
      of performance for a more complex analogical reasoning task. When solving
      relational reasoning problems based on discrete or discretized quantities,
      fractions yielded greater accuracy than decimals; in contrast, when quantities
      were continuous, accuracy was lower for both symbolic notations. Whereas previous
      research has established that decimals are more effective than fractions in
      supporting magnitude comparisons, the present study reveals that fractions are
      relatively advantageous in supporting relational reasoning with discrete (or
      discretized) concepts. These findings provide an explanation for the
      effectiveness of natural frequency formats in supporting some types of reasoning,
      and have implications for teaching of rational numbers.

PMID- 25384164
TI  - Working memory storage is intrinsically domain specific.
AB  - A longstanding debate in working memory (WM) is whether information is maintained
      in a central, capacity-limited storage system or whether there are domain
      specific stores for different modalities. This question is typically addressed by
      determining whether concurrent storage of 2 different memory arrays produces
      interference. Prior studies using this approach have shown at least some cost to
      maintaining 2 memory arrays that differed in perceptual modalities. However, it
      is not clear whether these WM costs resulted from competition for a central,
      capacity-limited store or from other potential sources of dual-task interference,
      such as task preparation and coordination, overlap in representational content
      (e.g., object vs. space based), or cognitive strategies (e.g., verbalization,
      chunking of the stimulus material in a higher order structure). In the present
      study we assess dual-task costs during the concurrent performance of a
      visuospatial WM task and an auditory object WM task when such sources of
      interference are minimized. The results show that performance of these 2 WM tasks
      are independent from each another, even at high WM load. Only when we introduced
      a common representational format (spatial information) to both WM tasks did dual
      task performance begin to suffer. These results are inconsistent with the notion
      of a domain-independent storage system, and suggest instead that WM is
      constrained by multiple domain-specific stores and central executive processes.
      Evidently, there is nothing intrinsic about the functional architecture of the
      human mind that prevents it from storing 2 distinct representations in WM, as
      long as these representations do not overlap in any functional domain.

PMID- 25384163
TI  - The social power of regret: the effect of social appraisal and anticipated
      emotions on fair and unfair allocations in resource dilemmas.
AB  - We investigated how another person's emotions about resource allocation decisions
      influence observers' resource allocations by influencing the emotions that
      observers anticipate feeling if they were to act in the same way. Participants
      were exposed to an exemplar who made a fair or unfair division in an economic
      game and expressed pride or regret about this decision. Participants then made
      their own resource allocation decisions. Exemplar regret about acting fairly
      decreased the incidence of fair behavior (Studies 1A and 1B). Likewise, exemplar
      regret about acting unfairly increased the incidence of fair behavior (Study 2).
      The effect of others' emotions on observers' behavior was mediated by the
      observers' anticipated emotions. We discuss our findings in light of the view
      that social appraisal and anticipated emotions are important tools for social
      learning and may contribute to the formation and maintenance of social norms
      about greed and fairness.

PMID- 25384165
TI  - The relationship between action-effect monitoring and attention capture.
AB  - Many recent findings suggest that stimuli that are perceived to be the
      consequence of one's own actions are processed with priority. According to the
      preactivation account of intentional binding, predicted consequences are
      preactivated and hence receive a temporal advantage in processing. The
      implications of the preactivation account are important for theories of attention
      capture, as temporal advantage often translates to attention capture. Hence,
      action might modulate attention capture by feature singletons. Experiment 1
      showed that a motion onset and color change captured attention only when it was
      preceded by an action. Experiment 2 showed that the capture occurs only with
      predictable, but not with unpredictable, consequences of action. Experiment 3
      showed that even when half the display changed color at display transition, they
      were all prioritized. The results suggest that action modulates attentional
      control.

PMID- 25384166
TI  - Phonon black-body radiation limit for heat dissipation in electronics.
AB  - Thermal dissipation at the active region of electronic devices is a fundamental
      process of considerable importance. Inadequate heat dissipation can lead to
      prohibitively large temperature rises that degrade performance, and intensive
      efforts are under way to mitigate this self-heating. At room temperature, thermal
      resistance is due to scattering, often by defects and interfaces in the active
      region, that impedes the transport of phonons. Here, we demonstrate that heat
      dissipation in widely used cryogenic electronic devices instead occurs by phonon
      black-body radiation with the complete absence of scattering, leading to large
      self-heating at cryogenic temperatures and setting a key limit on the noise
      floor. Our result has important implications for the many fields that require
      ultralow-noise electronic devices. 

PMID- 25384167
TI  - Orbital-driven nematicity in FeSe.
AB  - A fundamental and unconventional characteristic of superconductivity in iron
      based materials is that it occurs in the vicinity of two other instabilities. In
      addition to a tendency towards magnetic order, these Fe-based systems have a
      propensity for nematic ordering: a lowering of the rotational symmetry while time
      reversal invariance is preserved. Setting the stage for superconductivity, it is
      heavily debated whether the nematic symmetry breaking is driven by lattice,
      orbital or spin degrees of freedom. Here, we report a very clear splitting of NMR
      resonance lines in FeSe at Tnem = 91 K, far above the superconducting Tc of 9.3
      K. The splitting occurs for magnetic fields perpendicular to the Fe planes and
      has the temperature dependence of a Landau-type order parameter. Spin-lattice
      relaxation rates are not affected at Tnem, which unequivocally establishes
      orbital degrees of freedom as driving the nematic order. We demonstrate that
      superconductivity competes with the emerging nematicity. 

PMID- 25384168
TI  - Layered memristive and memcapacitive switches for printable electronics.
AB  - Novel computing technologies that imitate the principles of biological neural
      systems may offer low power consumption along with distinct cognitive and
      learning advantages. The development of reliable memristive devices capable of
      storing multiple states of information has opened up new applications such as
      neuromorphic circuits and adaptive systems. At the same time, the explosive
      growth of the printed electronics industry has expedited the search for advanced
      memory materials suitable for manufacturing flexible devices. Here, we
      demonstrate that solution-processed MoOx/MoS2 and WOx/WS2 heterostructures
      sandwiched between two printed silver electrodes exhibit an unprecedentedly large
      and tunable electrical resistance range from 10(2) to 10(8) Omega combined with
      low programming voltages of 0.1-0.2 V. The bipolar resistive switching, with a
      concurrent capacitive contribution, is governed by an ultrathin (<3 nm) oxide
      layer. With strong nonlinearity in switching dynamics, different mechanisms of
      synaptic plasticity are implemented by applying a sequence of electrical pulses. 

PMID- 25384169
TI  - Actuation of shape-memory colloidal fibres of Janus ellipsoids.
AB  - Many natural micrometre-scale assemblies can be actuated to control their
      optical, transport and mechanical properties, yet such functionality is lacking
      in colloidal structures synthesized thus far. Here, we show with experiments and
      computer simulations that Janus ellipsoids can self-assemble into self-limiting
      one-dimensional fibres with shape-memory properties, and that the fibrillar
      assemblies can be actuated on application of an external alternating-current
      electric field. Actuation of the fibres occurs through a sliding mechanism that
      permits the rapid and reversible elongation and contraction of the Janus
      ellipsoid chains by ~36% and that on long timescales leads to the generation of
      long, uniform self-assembled fibres. Colloidal-scale actuation might be useful in
      microrobotics and in applications of shape-memory materials. 

PMID- 25384170
TI  - A novel system for the classification of diseased retinal ganglion cells.
AB  - Retinal ganglion cell (RGC) dendritic atrophy is an early feature of many forms
      of retinal degeneration, providing a challenge to RGC classification. The
      characterization of these changes is complicated by the possibility that
      selective labeling of any particular class can confound the estimation of
      dendritic remodeling. To address this issue we have developed a novel, robust,
      and quantitative RGC classification based on proximal dendritic features which
      are resistant to early degeneration. RGCs were labeled through the ballistic
      delivery of DiO and DiI coated tungsten particles to whole retinal explants of 20
      adult Brown Norway rats. RGCs were grouped according to the Sun classification
      system. A comprehensive set of primary and secondary dendrite features were
      quantified and a new classification model derived using principal component (PCA)
      and discriminant analyses, to estimate the likelihood that a cell belonged to any
      given class. One-hundred and thirty one imaged RGCs were analyzed; according to
      the Sun classification, 24% (n = 31) were RGCA, 29% (n = 38) RGCB, 32% (n = 42)
      RGCC, and 15% (n = 20) RGCD. PCA gave a 3 component solution, separating RGCs
      based on descriptors of soma size and primary dendrite thickness, proximal
      dendritic field size and dendritic tree asymmetry. The new variables correctly
      classified 73.3% (n = 74) of RGCs from a training sample and 63.3% (n = 19) from
      a hold out sample indicating an effective model. Soma and proximal dendritic tree
      morphological features provide a useful surrogate measurement for the
      classification of RGCs in disease. While a definitive classification is not
      possible in every case, the technique provides a useful safeguard against sample
      bias where the normal criteria for cell classification may not be reliable. 

PMID- 25384171
TI  - Inhibition of beta-Catenin enhances the anticancer effect of irreversible EGFR
      TKI in EGFR-mutated non-small-cell lung cancer with a T790M mutation.
AB  - INTRODUCTION: Patients with non-small-cell lung cancer (NSCLC) with somatic
      activating mutations of the epidermal growth factor receptor gene (EGFR
      mutations) generally respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs). beta
      Catenin is a key component of the Wnt/beta-Catenin signal and is an important
      oncogene that is involved in the pathogenesis and progression of malignant
      tumors, especially cancer stem cells. METHODS AND RESULTS: We found that EGFR
      mutated NSCLC cell lines exhibited a high expression level of beta-Catenin,
      compared with cell lines with the wild-type EGFR gene, and XAV939 (a beta-Catenin
      inhibitor) enhanced the sensitivities to EGFR-TKI in EGFR-mutated NSCLC cell
      lines. In EGFR-mutated NSCLC cell lines with the acquired resistance threonine-to
      methionine mutation in codon 790 (T790M) mutation, XAV939 enhanced the
      sensitivity of the cells to an irreversible EGFR-TKI but not a reversible EGFR
      TKI. The combination of XAV939 and EGFR-TKIs strongly inhibited the beta-Catenin
      signal and strongly decreased the phosphorylation of EGFR, compared with the use
      of EGFR-TKIs alone, suggesting an interaction between EGFR and the beta-Catenin
      signal. The stem cell-like properties of the EGFR-mutated cell line carrying the
      T790M mutation were inhibited by XAV939 and BIBW2992 (an irreversible EGFR-TKI).
      Furthermore, the stem cell-like properties were strongly inhibited by a
      combination of both the agents. A xenograft study demonstrated that beta-Catenin
      knockdown enhanced the antitumor effect of BIBW2992 in the EGFR-mutated NSCLC
      cell line carrying the T790M mutation. CONCLUSION: Our findings indicate that
      beta-Catenin might be a novel therapeutic target in EGFR-mutated NSCLC carrying
      the T790M mutation.

PMID- 25384172
TI  - A mass spectrometry assay to simultaneously analyze ROS1 and RET fusion gene
      expression in non-small-cell lung cancer.
AB  - INTRODUCTION: ROS1 and RET gene fusions were recently discovered in non-small
      cell lung cancer (NSCLC) as potential therapeutic targets with small-molecule
      kinase inhibitors. The conventional screening methods of these fusions are time
      consuming and require samples of high quality and quantity. Here, we describe a
      novel and efficient method by coupling the power of multiplexing polymerase chain
      reaction and the sensitivity of mass spectrometry. METHODS: The multiplex mass
      spectrometry platform simultaneously tests samples for the expression of nine
      ROS1 and six RET fusion genes. The assay incorporates detection of wild-type exon
      junctions immediately upstream and downstream of the fusion junction to exclude
      false-negative results. To flag false-positives, the system also comprises two
      independent assays for each fusion gene junction. RESULTS: The characteristic
      mass spectrometric peaks of the gene fusions were obtained using engineered
      plasmid constructs. Specific assays targeting the wild-type gene exon junctions
      were validated using complimentary DNA from lung tissue of healthy individuals.
      The system was further validated using complimentary DNA derived from NSCLC cell
      lines that express endogenous fusion genes. The expressed ROS1-SLC34A2 and CCDC6
      RET gene fusions from the NSCLC cell lines HCC78 and LC-2/ad, respectively, were
      accurately detected by the novel assay. The assay is extremely sensitive, capable
      of detecting an event in test specimens containing 0.5% positive tumors.
      CONCLUSION: The novel multiplexed assay is robustly capable of detecting 15
      different clinically relevant RET and ROS1 fusion variants. The benefits of this
      detection method include exceptionally low sample input, high cost efficiency,
      flexibility, and rapid turnover.

PMID- 25384173
TI  - A phase II study of induction chemotherapy followed by thoracic radiotherapy and
      erlotinib in poor-risk stage III non-small-cell lung cancer: results of CALGB
      30605 (Alliance)/RTOG 0972 (NRG).
AB  - INTRODUCTION: Patients with stage III non-small-cell lung cancer and poor
      performance status and/or weight loss do not seem to benefit from standard
      therapy. Based on the preclinical interaction between epidermal growth factor
      receptor inhibitors and radiation, we designed a trial of induction chemotherapy
      followed by thoracic radiotherapy and concurrent erlotinib. METHODS: Patients
      with poor-risk unresectable stage III non-small-cell lung cancer received two
      cycles of carboplatin at an AUC of 5 and nab-paclitaxel at 100 mg/m on days 1 and
      8 every 21 days, followed by erlotinib administered concurrently with thoracic
      radiotherapy. Maintenance was not permitted. Molecular analysis was performed in
      available specimens. Seventy-two eligible patients were required to test whether
      the 1-year survival rate was less than 50% or greater than or equal to 65% with
      approximately 90% power at a significance level of 0.10. RESULTS: From March 2008
      to October 2011, 78 patients were enrolled, three of whom were ineligible. The
      median age was 68 (range, 39-88) and 32% were aged greater than or equal to 75
      years. Patients were evenly distributed between stages IIIA and IIIB and the
      majority had performance status 2. The overall response rate was 67% and the
      disease control rate was 93%. Treatment was well tolerated. The median PFS and OS
      were 11 and 17 months, respectively. The overall 12-month OS was 57%, which
      narrowly missed the prespecified target for significance. CONCLUSIONS: Patients
      with poor-risk stage III non-small-cell lung cancer had better than expected
      outcomes with a regimen of induction carboplatin/nab-paclitaxel followed by
      thoracic radiotherapy and erlotinib. However, as per the statistical design, the
      12-month OS was not sufficiently high to warrant further studies.

PMID- 25384175
TI  - Reproducibility of histopathological diagnosis in poorly differentiated NSCLC:
      statistical issue.

PMID- 25384174
TI  - Lack of association between the BIM deletion polymorphism and the risk of lung
      cancer with and without EGFR mutations.
AB  - INTRODUCTION: The BIM deletion polymorphism in intron 2 was found in a
      significant percent of the Asian population. Patients with epidermal growth
      factor receptor (EGFR) mutant lung cancers harboring this BIM polymorphism have
      shorter progression free survival and overall response rates to EGFR tyrosine
      kinase inhibitors. However, the association between the BIM deletion polymorphism
      and lung cancer risk is unknown. METHODS: The BIM deletion polymorphism was
      screened by polymerase chain reaction in 765 lung cancer cases and 942 healthy
      individuals. RESULTS: Carriers possessing one allele of the BIM polymorphism were
      observed in 13.0% of control cases and 12.8% of lung cancer cases, similar to
      incidence rates reported earlier in healthy individuals. Homozygote for the BIM
      polymorphism was observed in four of 942 healthy controls and three of 765 lung
      cancer cases. The frequency of the BIM deletion polymorphism in lung cancer
      patients was not related to age, sex, smoking history, or family history of lung
      cancer. The BIM deletion polymorphism was found in 30 of 212 patients with EGFR
      wild type lung cancers and 16 of 120 patients with EGFR mutant lung cancers. The
      frequency of the BIM polymorphism is similar between cancers with wild type EGFR
      and mutated EGFR (p = 0.78). CONCLUSION: The BIM deletion polymorphism was not
      associated with lung cancer susceptibility. Furthermore, the BIM polymorphism is
      not associated with EGFR mutant lung cancer.

PMID- 25384176
TI  - Cardiac screening of young athletes prior to participation in sports:
      difficulties in detecting the fatally flawed among the fabulously fit.
AB  - Deaths of young athletes from cardiac disease are uncommon but receive
      considerable media attention and intermittently galvanize debates about cardiac
      screening prior to participation in sports. Both the American Heart Association
      (AHA) and European Society of Cardiology (ESC) endorse preparticipation screening
      in athletes; however, there is disagreement about the best approach. The AHA
      recommends history and physical examination; this approach is pragmatic and
      relatively inexpensive but has poor sensitivity because most athletes are
      asymptomatic and physical examination identifies only a minority of those at risk
      of sudden cardiac death. The inclusion of the electrocardiogram in accordance
      with the recommendations of the ESC improves sensitivity for detection of serious
      cardiac disease but is associated with an unacceptably high false-positive rate,
      in part because of the overlap between the electrical manifestations of athletic
      training and the cardiomyopathies. For young athletes with normal
      electrocardiogram results, echocardiography contributes minimally to the
      diagnosis of serious cardiac diseases. Given all the complexities, cardiac
      screening of young athletes should be voluntary not mandatory and conducted by
      highly experienced physicians who fully understand the cardiovascular adaptation
      to intensive exercise. 

PMID- 25384177
TI  - Direct asymmetric hydrogenation of alpha-keto acids by using the highly efficient
      chiral spiro iridium catalysts.
AB  - A new efficient and highly enantioselective direct asymmetric hydrogenation of
      alpha-keto acids employing the Ir/SpiroPAP catalyst under mild reaction
      conditions has been developed. This method might be feasible for the preparation
      of a series of chiral alpha-hydroxy acids on a large scale. 

PMID- 25384179
TI  - The first near-linear bis(amide) f-block complex: a blueprint for a high
      temperature single molecule magnet.
AB  - We report the first near-linear bis(amide) 4f-block compound and show that this
      novel structure, if implemented with dysprosium(III), would have unprecedented
      single molecule magnet (SMM) properties with an energy barrier, Ueff, for
      reorientation of magnetization of 1800 cm(-1).

PMID- 25384178
TI  - Site-selective C(sp3)-H functionalization of di-, tri-, and tetrapeptides at the
      N-terminus.
AB  - Although the syntheses of novel and diverse peptides rely mainly on traditional
      coupling using unnatural amino acids, postsynthetic modification of peptides
      could provide a complementary method for the preparation of nonproteinogenic
      peptides. Site selectivity of postsynthetic modification of peptides is usually
      achieved by targeting reactive moieties, such as the thiol group of cysteine or
      the C-2 position of tryptophan. Herein, we report the development of site
      selective functionalizations of inert C(sp(3))-H bonds of N-terminal amino acids
      in di-, tri-, and tetrapeptides without installing a directing group. The native
      amino acid moiety within the peptide is used as a ligand to accelerate the C-H
      activation reaction. In the long run, this newly uncovered reactivity could
      provide guidance for developing site-selective C(sp(3))-H activation toward
      postsynthetic modification of a broader range of peptides. 

PMID- 25384180
TI  - Pregnancy outcomes and prognostic factors in patients with intrahepatic
      cholestasis of pregnancy.
AB  - The aim of this study was to describe maternal and fetal characteristics
      associated with intrahepatic cholestasis of pregnancy (ICP) and to determine
      clinical and biochemical predictors of fetal complications. A total of 89
      singleton pregnancies with ICP were analysed, retrospectively. All data
      concerning laboratory results, symptom onset time, treatment response, delivery
      time and infant information were recorded in the study protocol. The mean
      gestational age at diagnosis was 32.6 +/- 3.4 weeks; mean time of delivery was
      36.8 +/- 1.9 weeks. Binary logistic regression revealed that gestational age at
      diagnosis was predictive of preterm delivery (OR = 2.3, 95% CI: 1.5-3.3, p =
      0.001). The incidence of respiratory distress syndrome (RDS), fetal growth
      restriction, fetal distress and preterm delivery were significantly higher in
      patients who were diagnosed before 30 weeks than after 34 weeks' gestation (p <
      0.01). Gestational age at diagnosis is an important independent factor predicting
      adverse perinatal outcomes in patients with ICP. 

PMID- 25384182
TI  - Axonal ion channel dysfunction in c9orf72 familial amyotrophic lateral sclerosis.
AB  - IMPORTANCE: Abnormalities of axonal excitability characterized by upregulation of
      persistent sodium (Na+) conductances and reduced potassium (K+) currents have
      been reported in sporadic amyotrophic lateral sclerosis (SALS) phenotypes and
      linked to the development of clinical features such as fasciculations and
      neurodegeneration. OBJECTIVE: To investigate whether abnormalities of axonal ion
      channel function, particularly upregulation of persistent Na+ conductances and
      reduced K+ currents, form the pathophysiological basis of chromosome 9 open
      reading frame 72 (c9orf72) familial amyotrophic lateral sclerosis (FALS). DESIGN,
      SETTING, AND PARTICIPANTS: This was a prospective study. Clinical and functional
      assessment, along with motor-nerve excitability studies, were undertaken in 10
      clinically affected patients with c9orf72 FALS, 9 asymptomatic c9orf72 mutation
      carriers, and 21 patients with SALS from 3 hospitals and 2 outpatient clinics.
      MAIN OUTCOMES AND MEASURES: Axonal excitability variables were measured in
      patients with c9orf72 ALS and results compared with matched patients with SALS
      and healthy control participants. RESULTS: Strength-duration time constant
      (tauSD) was significantly increased in the patients with c9orf72 FALS and those
      with SALS (mean [SD], c9orf72 FALS: 0.50 [0.02] milliseconds; SALS: 0.52 [0.02]
      milliseconds; P < .01) when compared with control participants (mean [SD], 0.44
      [0.01] milliseconds). In contrast, there were no significant changes of tauSD in
      asymptomatic c9orf72 mutation carriers (P = .42). An accompanying increase in
      depolarizing threshold electrotonus at 90 to 100 milliseconds (TEd 90-100
      milliseconds) was also evident in the c9orf72 FALS (P < .05) and SALS (P < .01)
      cohorts. Mathematical modeling suggested that an increase in persistent Na+
      conductances, along with reduced K+ currents, best explained the changes in
      axonal excitability. Importantly, these abnormalities in axonal excitability
      correlated with the motor amplitude (tauSD: R = -0.38, P < .05 and TEd 90-100
      milliseconds: R = -0.44, P < .01), muscle weakness (TEd 90-100 milliseconds: R = 
      0.32, P < .05), and the ALS Functional Rating Scale (TEd 90-100 milliseconds: R =
      -0.34, P < .05). CONCLUSIONS AND RELEVANCE: Findings from the present study
      establish that upregulation of persistent Na+ conductances and reduced K+
      currents were evident in both c9orf72 FALS and SALS cohorts, and these changes in
      axonal excitability were associated with motor neuron degeneration.

PMID- 25384183
TI  - When the rubber meets the road: adherence and persistence with non-vitamin K
      antagonist oral anticoagulants and old oral anticoagulants in the real world-a
      problem or a myth ?
AB  - For patients taking vitamin K antagonist (VKA) anticoagulants, poor adherence to
      the drug regimen is associated with a lower percent time in therapeutic range and
      also with an increased risk of thromboembolic complications. The non-vitamin K
      antagonist oral anticoagulants (NOACs) do not require routine laboratory
      monitoring and therefore the risk of nonadherence remaining undetected and
      without any corrective attempts must be recognized. Persistence with the NOACs
      and VKA was quite comparable in the phase III trials, whereas a postmarketing
      study demonstrated better persistence with dabigatran than with warfarin.
      Preliminary studies on adherence to the dabigatran regimen have shown poor
      adherence in 12 to 27%, and also for this drug such behavior seems associated
      with an unfavorable outcome. There is uncertainty about the best methods to
      evaluate adherence. Studies on the adherence are needed for all the NOACs, for
      different clinical settings and patient populations. A combination of strategies
      should probably be used to achieve the best possible adherence, including patient
      education and some form of automatic reminders. 

PMID- 25384184
TI  - Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13
      years in China.
AB  - BACKGROUND: Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but
      serious complication of ATD therapy. The characteristics of severe hepatotoxicity
      have been reported in only a small number of patients. METHOD: Ninety patients
      with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000
      2013) who were about to undergo nuclear medicine therapy with (131)I from a
      sample of 8864 patients with hyperthyroidism were studied, and the outcomes were
      evaluated. RESULTS: The mean age of the patients with ATD-induced severe
      hepatotoxicity was 41.6+/-12.5 years (mean+/-standard deviation), and the female
      to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1+/
      7.4 mg/day. The propylthiouracil (PTU) dose given at the onset was 212.8+/-105.0
      mg/day. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of
      patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The
      types of severe hepatotoxicity did not differ significantly between the MMI and
      PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group
      (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these
      frequencies were not significantly different (p=0.069). The patients who were
      treated with (131)I received an average dose of 279.1+/-86.1 MBq (n=84). Therapy
      was successful in 60 of the 67 patients (89.6%). The success rate was equivalent
      (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31).
      CONCLUSIONS: Severe hepatotoxicity tends to occur within the first three months
      after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did
      not differ between the MMI and PTU groups. (131)I therapy is an effective
      treatment approach for patients with ATD-induced severe hepatotoxicity.

PMID- 25384188
TI  - Biotemplate synthesis of polyaniline@cellulose nanowhiskers/natural rubber
      nanocomposites with 3D hierarchical multiscale structure and improved electrical
      conductivity.
AB  - Development of novel and versatile strategies to construct conductive polymer
      composites with low percolation thresholds and high mechanical properties is of
      great importance. In this work, we report a facile and effective strategy to
      prepare polyaniline@cellulose nanowhiskers (PANI@CNs)/natural rubber (NR)
      nanocomposites with 3D hierarchical multiscale structure. Specifically, PANI was
      synthesized in situ on the surface of CNs biotemplate to form PANI@CNs
      nanohybrids with high aspect ratio and good dispersity. Then NR latex was
      introduced into PANI@CNs nanohybrids suspension to enable the self-assembly of
      PANI@CNs nanohybrids onto NR latex microspheres. During cocoagulation process,
      PANI@CNs nanohybrids selectively located in the interstitial space between NR
      microspheres and organized into a 3D hierarchical multiscale conductive network
      structure in NR matrix. The combination of the biotemplate synthesis of PANI and
      latex cocoagulation method significantly enhanced the electrical conductivity and
      mechanical properties of the NR-based nanocomposites simultaneously. The
      electrical conductivity of PANI@CNs/NR nanocomposites containing 5 phr PANI
      showed 11 orders of magnitude higher than that of the PANI/NR composites at the
      same loading fraction,; meanwhile, the percolation threshold was drastically
      decreased from 8.0 to 3.6 vol %.

PMID- 25384187
TI  - Drugging sphingosine kinases.
AB  - The transfer of the gamma phosphate from ATP to sphingosine (Sph) to generate a
      small signaling molecule, sphingosine 1-phosphate (S1P), is catalyzed by
      sphingosine kinases (SphK), which exist as two isoforms, SphK1 and SphK2. SphK is
      a key regulator of S1P and the S1P:Sph/ceramide ratio. Increases in S1P levels
      have been linked to diseases including sickle cell disease, cancer, and fibrosis.
      Therefore, SphKs are potential targets for drug discovery. However, the current
      chemical biology toolkit needed to validate these enzymes as drug targets is
      inadequate. With this review, we survey in vivo active SphK inhibitors and
      highlight the need for developing more potent and selective inhibitors. 

PMID- 25384190
TI  - Lifetime Characteristics of Evening-Preference and Irregular Bed-Rise Time Are
      Associated With Lifetime Seasonal Variation of Mood and Behavior: Comparison
      Between Individuals With Bipolar Disorder and Healthy Controls.
AB  - Sleep-wake cycle disruption and seasonal variation in mood and behavior have been
      associated with mood disorders. This study aimed to investigate the lifetime
      characteristics of the sleep-wake cycle and its association with the lifetime
      characteristics of seasonality in individuals with bipolar disorder. Circadian
      preference, regularity of bed-rise time, and seasonality were evaluated on a
      lifetime basis using the Composite Scale of Morningness, the Sleep Timing
      Questionnaire, and the Seasonal Pattern Assessment Questionnaire in clinically
      stable individuals with bipolar I/II disorders (n = 103/97) and healthy controls
      (n = 270). Bipolar groups were more likely to have evening preference and
      irregular bed-rise time. These characteristics were interrelated and,
      particularly, more prevalent in bipolar II disorder. Seasonality, which was also
      more prevalent in the bipolar groups, was associated with evening preference and
      irregularity of the weekday bed-rise time. 

PMID- 25384191
TI  - Breaking aggregation in a tetrathiafulvalene-fused zinc porphyrin by metal-ligand
      coordination to form a donor-acceptor hybrid for ultrafast charge separation and
      charge stabilization.
AB  - A novel electron rich, tetrathiafulvalene fused zinc porphyrin, (TTF)4PZn, has
      been newly synthesized and characterized using spectral and electrochemical
      methods. In spite of the presence of eight t-butyl groups, (TTF)4PZn exhibited
      appreciable aggregation in solution. Scanning electron microscopic (SEM) imaging
      of the aggregates revealed their spherical particulate morphology. Attenuation of
      intermolecular aggregation was possible by metal-ligand coordination of a
      nitrogenous ligand. Further, using this strategy, a donor-acceptor hybrid was
      formed by coordinating imidazole functionalized fullerene as an electron
      acceptor. The occurrence of intrasupramolecular ultrafast photoinduced charge
      separation has been established using fluorescence and transient absorption
      spectroscopic techniques. The determined rate of charge separation, kCS, and rate
      of charge recombination, kCR were found to be 1.4 * 10(11) s(-1) and 2.5 * 10(6)
      s(-1), respectively. The lower kCR values indicate charge stabilization in the
      assembled donor-acceptor conjugate via an electron transfer-hole transfer
      mechanism. 

PMID- 25384189
TI  - Resistance patterns associated with HCV NS5A inhibitors provide limited insight
      into drug binding.
AB  - Direct-acting antivirals (DAAs) have significantly improved the treatment of
      infection with the hepatitis C virus. A promising class of novel antiviral agents
      targets the HCV NS5A protein. The high potency and broad genotypic coverage are
      favorable properties. NS5A inhibitors are currently assessed in advanced clinical
      trials in combination with viral polymerase inhibitors and/or viral protease
      inhibitors. However, the clinical use of NS5A inhibitors is also associated with
      new challenges. HCV variants with decreased susceptibility to these drugs can
      emerge and compromise therapy. In this review, we discuss resistance patterns in
      NS5A with focus prevalence and implications for inhibitor binding.

PMID- 25384192
TI  - The interaction of propionic and butyric acids with ice and HNO3-doped ice
      surfaces at 195-212 K.
AB  - The interaction of propionic and butyric acids on ice and HNO3-doped ice were
      studied between 195 and 212 K and low concentrations, using a Knudsen flow
      reactor coupled with a quadrupole mass spectrometer. The initial uptake
      coefficients (gamma0) of propionic and butyric acids on ice as a function of
      temperature are given by the expressions: gamma0(T) = (7.30 +/- 1.0) * 10(-10)
      exp[(3216 +/- 478)/T] and gamma0(T) = (6.36 +/- 0.76) * 10(-11) exp[(3810 +/-
      434)/T], respectively; the quoted error limits are at 95% level of confidence.
      Similarly, gamma0 of propionic acid on 1.96 wt % (A) and 7.69 wt % (B) HNO3-doped
      ice with temperature are given as gamma(0,A)(T) = (2.89 +/- 0.26) * 10(-8)
      exp[(2517 +/- 266)/T] and gamma(0,B)(T) = (2.77 +/- 0.29) * 10(-7) exp[(2126 +/-
      206)/T], respectively. The results show that gamma0 of C1 to C4 n-carboxylic
      acids on ice increase with the alkyl-group length, due to lateral interactions
      between alkyl-groups that favor a more perpendicular orientation and well packing
      of H-bonded monomers on ice. The high uptakes (>10(15) molecules cm(-2)) and long
      recovery signals indicate efficient growth of random multilayers above the first
      monolayer driven by significant van der Waals interactions. The heterogeneous
      loss of both acids on ice and HNO3-doped ice particles in dense cirrus clouds is
      estimated to take a few minutes, signifying rapid local heterogeneous removal by
      dense cirrus clouds.

PMID- 25384193
TI  - Coadministration of black seeds and turmeric shows enhanced efficacy in
      preventing metabolic syndrome in fructose-fed rats.
AB  - Among noncommunicable diseases, metabolic syndrome (MS), a cluster of metabolic
      disorders including obesity, hyperglycemia, hyperlipidemia and hypertension, is
      highly prevalent in modern society. Its management requires lifestyle
      modifications and/or the life-long use of multiple medications, hence demanding
      development of safe alternative remedies. This study was aimed to establish the
      efficacy of combined use of black seeds and turmeric using fructose-fed rat model
      of MS. The high-performance liquid chromatographic fingerprints of turmeric and
      black seeds showed the presence of curcumin and thymoquinone, respectively, as
      their major constitutes. Different doses of black seeds and turmeric,
      individually and in combination, were administered to fructose-fed rats for up to
      6 weeks representing characteristic features of MS. At 3 weeks of the treatment,
      black seeds and turmeric lowered (P < 0.01) high blood pressure and low-density
      lipoprotein cholesterol, respectively, whereas their coadministration reduced (P
      < 0.01) both high blood pressure and hypertriglyceridemia. At 6 weeks, the
      coadministration of both herbs, at half the doses of individual herbs, was the
      most effective (P < 0.001) in preventing hypertension, hyperglycemia,
      dyslipidemia, hyperinsulinemia, and endothelial dysfunction than the individual
      herbs. This study demonstrates the therapeutic superiority of the combination of
      black seeds and turmeric at low doses over individually tested herbs, in
      improving features of MS.

PMID- 25384194
TI  - Pharmacological characterization of the vasodilating effect induced by the
      ruthenium complex cis-[Ru(NO)(NO2)(bpy)2].(PF6)2.
AB  - Nitric oxide (NO) can be found in different species and is a potent vasodilator.
      The ruthenium compound cis-[Ru(NO)(NO2)(bpy)2].(PF6)2 (BPY) can generate NO. This
      study aimed to investigate the BPY stability at physiological pH, the cellular
      mechanisms involved in BPY effect, NO species originating from BPY, and to verify
      how BPY affects blood pressure. Our results has shown that at pH 7.4 and 9.4, the
      NO coordinated to ruthenium (Ru-NO) is converted to nitrite (Ru-NO2) and remains
      stable. In aortic rings, the stable configuration of BPY (Ru-NO2) induces
      vascular relaxation in a concentration-dependent manner. Thus, further
      experiments were made with stable configuration of BPY (Ru-NO2). The relaxation
      induced by BPY was abolished in the presence of guanylyl cyclase inhibitor and
      decreased in the presence of potassium channel blocker. By using radicalar (NO)
      and nitroxyl (NO) scavenger, our results suggest that the BPY mainly release the
      radicalar species. By using fluorescence probes to detect intracellular NO
      concentration ([NO]i) and cytosolic Ca concentration ([Ca]c), we verified that in
      smooth muscle cells, BPY induces an increase in [NO]i and a decrease in [Ca]c.
      The intravenous bolus injection of 1.25, 2.5, and 5.0 mg/kg from stable
      configuration of BPY results in a decrease on basal blood pressure values. Taken
      together, our results indicated that the stable configuration of the compound BPY
      induces vascular relaxation in aorta because of NO release and decrease of [Ca]c
      in vascular smooth muscle cells. Also, the stable configuration is able to reduce
      the blood pressure in a dose-dependent manner.

PMID- 25384195
TI  - Cerebral circulation: function and dysfunction in Alzheimer's disease.
AB  - Alzheimer's disease is a neurodegenerative disease associated with a
      cerebrovascular pathology partly imputed to increased brain levels of amyloid
      beta (Abeta) peptide and transforming growth factor-beta1 (TGF-beta1). Using
      transgenic mice that overproduce Abeta (APP mice) or TGF-beta1 (TGF mice), we
      found that both induce impairments of cerebrovascular function and structural
      changes of the vessel wall. Soluble Abeta species affect blood vessel primarily
      by increasing oxidative stress, which results in reduced nitric oxide-mediated
      dilations and impaired signaling of endothelial transient receptor potential
      vanilloid type 4 and smooth muscle KATP channels. These impairments occur early
      in the disease process and can be rescued by either antioxidants (Tempol, N
      acetylcysteine) or therapy with antioxidant properties (simvastatin). In
      contrast, comparable impairments in TGF mice were insensitive to antioxidants and
      could only be rescued by therapy with pleiotropic effects. The blood flow
      response evoked by whisker stimulation was impaired in both APP and TGF mice. In
      contrast, the cerebral uptake of glucose induced by this stimulus was reduced
      only in APP mice, pointing to preserved neuronal function in the TGF mice.
      Accordingly, despite similar but mechanistically different cerebrovascular
      deficits in APP and TGF mice, overt cognitive deficits were seen only in APP mice
      and could be rescued depending on age. 

PMID- 25384196
TI  - Protective Effects of Glucagon-like Peptide 1 on Endothelial Function in
      Hypertension.
AB  - Vascular endothelial cells play a major role in maintaining cardiovascular
      homeostasis. Endothelial dysfunction, characterized by reduced endothelium
      dependent relaxations or accompanied by enhanced endothelium-dependent
      contractions, is a hallmark of and plays a pivotal role in the pathogenesis of
      hypertension. Endothelial dysfunction in hypertension has been linked to
      decreases in nitric oxide (NO) bioavailability, reflecting the impaired
      generation of NO and/or the enhanced inactivation of NO by reactive oxygen
      species. Many of these conditions can be improved by glucagon-like peptide 1 (GLP
      1), a proglucagon-derived hormone secreted by intestinal endocrine L-type cells,
      which is rapidly inactivated by an enzyme dipeptidyl peptidase 4 in circulation.
      On one hand, GLP-1 analogues or dipeptidyl peptidase 4 inhibitors upregulate
      endothelial nitric oxide synthase expression and increase endothelial nitric
      oxide synthase phosphorylation, resulting in improved production of NO and thus
      endothelium-dependent relaxations. On the other hand, GLP-1 and related agents
      attenuate endothelium-dependent contractions by reducing reactive oxygen species
      generation and cyclooxygenase-2 expression. GLP-1 elevating agents and GLP-1
      receptor agonists improve endothelial function in hypertension, suggesting that
      GLP-1 signaling could be a therapeutic target in hypertension-related vascular
      events. 

PMID- 25384197
TI  - MicroRNA Signature and Cardiovascular Dysfunction.
AB  - The worldwide increase in the prevalence of obesity and type 2 diabetes and the
      associated elevated risk of cardiovascular disease (CVD) has emphasized the need
      to seek new therapeutic targets to offset the negative impact on human health
      outcomes. In this regards, microRNAs (miRNAs), a class of small noncoding RNAs
      that mediate posttranscriptional gene silencing, have received considerable
      interest. miRNAs repress gene expression by their ability to pair with target
      sequences in the 3' untranslated region of the messenger RNA. miRNAs play a
      crucial role in the biogenesis and function of the cardiovascular system and are
      implicated as dynamic regulators of cardiac and vascular signaling and
      pathophysiology. Numerous miRNAs have been identified as novel biomarkers and
      potential therapeutic targets for CVD. In this review, we discuss the
      contribution of miRNAs to the regulation of CVD, their role in
      macrovascular/microvascular (dys)function, their potential as important
      biomarkers for the early detection of CVD, and, finally, as therapeutic targets. 

PMID- 25384198
TI  - Long chain fatty acid acylated derivatives of quercetin-3-o-glucoside as
      antioxidants to prevent lipid oxidation.
AB  - Flavonoids have shown promise as natural plant-based antioxidants for protecting
      lipids from oxidation. It was hypothesized that their applications in lipophilic
      food systems can be further enhanced by esterification of flavonoids with fatty
      acids. Quercetin-3-O-glucoside (Q3G) was esterified individually with six
      selected long chain fatty acids: stearic acid (STA), oleic acid (OLA), linoleic
      acid (LNA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and
      decosahexaenoic acid (DHA), using Candida antarctica B lipase as the biocatalyst.
      The antioxidant activity of esterified flavonoids was evaluated using lipid
      oxidation model systems of poly-unsaturated fatty acids-rich fish oil and human
      low density lipoprotein (LDL), in vitro. In the oil-in-water emulsion, Q3G esters
      exhibited 50% to 100% inhibition in primary oxidation and 30% to 75% inhibition
      in secondary oxidation. In bulk oil, Q3G esters did not provide considerable
      protection from lipid oxidation; however, Q3G demonstrated more than 50%
      inhibition in primary oxidation. EPA, DHA and ALA esters of Q3G showed
      significantly higher inhibition in Cu2+- and peroxyl radical-induced LDL
      oxidation in comparison to Q3G. 

PMID- 25384199
TI  - Grammatical number elicits SNARC and MARC effects as a function of task demands.
AB  - Despite the robustness of the spatial-numerical association of response codes
      (SNARC) and linguistic markedness of response codes (MARC) effect, the mechanisms
      that underlie these effects are still under debate. In this paper, we investigate
      the extraction of quantity information from German number words and nouns
      inflected for singular and plural using two alternative forced choice paradigms.
      These paradigms are applied to different tasks to investigate how access to
      quantity representation is modulated by task demands. In Experiment 1, we
      replicated previous SNARC findings for number words-that is, a relative left-hand
      advantage for words denoting small numbers and a right-hand advantage for words
      denoting large numbers in semantic tasks (parity decision and quantity
      comparison). No SNARC effect was obtained for surface or lexical processing tasks
      (font categorization and lexical decision). In Experiment 2, we found that German
      words inflected for singular had a relative left-hand advantage, and German words
      inflected for plural a relative right-hand advantage, showing a SNARC-like effect
      for grammatical number. The effect interfered, however, with a MARC-like effect
      based on the markedness asymmetry of singulars and plurals. These two effects
      appear to be dissociated by response latency rather than task demands, with MARC
      being more pronounced in early responses and SNARC being more pronounced in late
      responses. The present findings shed light on the relationship of conceptual
      number and grammatical number and constrain current accounts of the SNARC and
      MARC effects. 

PMID- 25384200
TI  - Reliability of the Cooking Task in adults with acquired brain injury.
AB  - Acquired brain injury (ABI) often leads to deficits in executive functioning (EF)
      responsible for severe and long-standing disabilities in daily life activities.
      The Cooking Task is an ecological and valid test of EF involving multi-tasking in
      a real environment. Given its complex scoring system, it is important to
      establish the tool's reliability. The objective of the study was to examine the
      reliability of the Cooking Task (internal consistency, inter-rater and test
      retest reliability). A total of 160 patients with ABI (113 men, mean age 37
      years, SD = 14.3) were tested using the Cooking Task. For test-retest
      reliability, patients were assessed by the same rater on two occasions (mean
      interval 11 days) while two raters independently and simultaneously observed and
      scored patients' performances to estimate inter-rater reliability. Internal
      consistency was high for the global scale (Cronbach alpha = .74). Inter-rater
      reliability (n = 66) for total errors was also high (ICC = .93), however the test
      retest reliability (n = 11) was poor (ICC = .36). In general the Cooking Task
      appears to be a reliable tool. The low test-retest results were expected given
      the importance of EF in the performance of novel tasks. 

PMID- 25384201
TI  - Osteoconductivity and osteoinductivity of porous hydroxyapatite coatings
      deposited by liquid precursor plasma spraying: in vivo biological response study.
AB  - The beneficial effect of a porous structure on the biological functions of
      calcium phosphate bulk ceramic or scaffold has been well documented.
      Nevertheless, the effect of a porous structure on the in vivo performance of
      hydroxyapatite (HA) coatings has been rarely reported, partly due to the
      difficulty in synthesizing porous HA coatings suitable for commercial
      applications. In this study, we have carried out a systematic in vivo study of
      porous HA-coated Ti implants (with and without surface modification) prepared by
      the liquid precursor plasma spraying process, in terms of its osteoconductivity
      and osteoinductivity. The results suggest the clear advantage of the porous
      structure over the dense structure, despite the pore structure (about 48%
      porosity and less than 100 MUm average pore size) being far from the ideal pore
      structure reported for bulk ceramic. The porous HA-coated implant significantly
      promotes early bone ingrowth at the pre-generated defective region, and early
      fixation at the bone-implant interface, especially at early implantation time
      (one month), showing about 120% and 40% increases respectively over those of the
      dense HA-coated implants prepared by the conventional atmospheric plasma spraying
      process. Moreover, the porous structure can be readily used to incorporate
      collagen/rh-BMP2, which demonstrates clear ectopic bone formation. Overall, the
      results suggest the augmentation of bone ingrowth is significant for HA coatings
      with a porous structure, which is critical for the early fixation and long-term
      stability of medical implants.

PMID- 25384202
TI  - Overcoming asymmetric goals in teams: the interactive roles of team learning
      orientation and team identification.
AB  - Although members of teams share a common, ultimate objective, they often have
      asymmetric or conflicting individual goals that shape the way they contribute to,
      and pursue, the shared goal of the team. Compounding this problem, they are
      frequently unaware of the nature of these goal asymmetries or even the fact that
      such differences exist. Drawing on, and integrating, social interdependence and
      representational gaps theories, we identify 2 emergent states that combine
      interactively to enable teams to overcome asymmetric goals: team identification
      and team learning orientation. Using data from long-term, real-life teams that
      engaged in a computer simulation designed to create both asymmetric goals and
      representational gaps about those goals, we found that teams were most effective
      when they had a high learning orientation coupled with high team identification
      and that this effect was mediated by teams' ability to form more accurate team
      goal mental models and engage in effective planning processes. Implications for
      theory and practice are discussed.

PMID- 25384203
TI  - When regulating emotions at work pays off: a diary and an intervention study on
      emotion regulation and customer tips in service jobs.
AB  - We investigated the relationship between deep acting, automatic regulation and
      customer tips with 2 different study designs. The first study was a daily diary
      study using a sample of Dutch waiters and taxi-drivers and assessed the link of
      employees' daily self-reported levels of deep acting and automatic regulation
      with the amount of tips provided by customers (N = 166 measurement occasions
      nested in 34 persons). Whereas deep acting refers to deliberate attempts to
      modify felt emotions and involves conscious effort, automatic regulation refers
      to automated emotion regulatory processes that result in the natural experience
      of desired emotions and do not involve deliberate control and effort. Multilevel
      analyses revealed that both types of emotion regulation were positively
      associated with customer tips. The second study was an experimental field study
      using a sample of German hairdressers (N = 41). Emotion regulation in terms of
      both deep acting and automatic regulation was manipulated using a brief self
      training intervention and daily instructions to use cognitive change and
      attentional deployment. Results revealed that participants in the intervention
      group received significantly more tips than participants in the control group.

PMID- 25384204
TI  - Tightening up the performance-pay linkage: roles of contingent reward leadership
      and profit-sharing in the cross-level influence of individual pay-for
      performance.
AB  - Drawing upon line-of-sight (Lawler, 1990, 2000; Murphy, 1999) as a unifying
      concept, we examine the cross-level influence of organizational use of individual
      pay-for-performance (PFP), theorizing that its impact on individual employees'
      performance-reward expectancy is boosted by the moderating effects of immediate
      group managers' contingent reward leadership and organizational use of profit
      sharing. Performance-reward expectancy is then expected to mediate the
      interactive effects of individual PFP with contingent reward leadership and
      profit-sharing on employee job performance. Analyses of cross-organizational and
      cross-level data from 912 employees in 194 workgroups from 45 companies reveal
      that organizations' individual PFP was positively related to employees'
      performance-reward expectancy, which was strengthened when it was accompanied by
      higher levels of contingent reward leadership and profit-sharing. Also,
      performance-reward expectancy significantly transmitted the effects of individual
      PFP onto job performance under higher levels of contingent reward leadership and
      profit-sharing, thus delineating cross-level mediating and moderating processes
      by which organizations' individual PFP is linked to important individual-level
      employee outcomes. Several theoretical and practical implications are discussed.

PMID- 25384205
TI  - Sleepiness at work: a review and framework of how the physiology of sleepiness
      impacts the workplace.
AB  - Sleepiness, the biological drive to sleep, is an important construct for the
      organizational sciences. This physiological phenomenon has received very little
      attention in the organizational science literature in spite of the fact that it
      influences a wide variety of workplace behaviors. In this article, we develop a
      framework through which sleepiness can be fruitfully studied. We describe (a)
      what sleepiness is and how it can be differentiated conceptually from related
      concepts such as fatigue, (b) the physiological basis of sleepiness, (c)
      cognitive and affective mechanisms that transmit the effects of sleepiness, and
      (d) the behavioral manifestations of sleepiness in the workplace. We also
      describe (e) job demand characteristics that are antecedents of sleepiness and
      (f) individual differences that moderate the aforementioned relationships.
      (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 25384207
TI  - An improved organic/inorganic solid receptor for colorimetric cyanide
      chemosensing in water: towards new mechanism aspects, simplistic use and
      portability.
AB  - A heterogeneous reaction-based colorimetric chemodosimeter toward cyanide anions
      was designed based on a hybrid pyrylium/alumina probe which possesses a great
      selectivity for CN(-) over other common anions even at significantly higher
      concentrations. The synergistic incorporation of the inorganic matrix and the
      organic receptor can play a pivotal role in the convenient field-usable
      determination of this toxic anion in water. Moreover, the catalytic properties
      coming from the inorganic matrix can greatly amplify the sensor performance. 

PMID- 25384208
TI  - Establishment, characterization, and toxicological application of loggerhead sea
      turtle (Caretta caretta) primary skin fibroblast cell cultures.
AB  - Pollution is a well-known threat to sea turtles but its impact is poorly
      understood. In vitro toxicity testing presents a promising avenue to assess and
      monitor the effects of environmental pollutants in these animals within the legal
      constraints of their endangered status. Reptilian cell cultures are rare and, in
      sea turtles, largely derived from animals affected by tumors. Here we describe
      the full characterization of primary skin fibroblast cell cultures derived from
      biopsies of multiple healthy loggerhead sea turtles (Caretta caretta), and the
      subsequent optimization of traditional in vitro toxicity assays to reptilian
      cells. Characterization included validating fibroblast cells by morphology and
      immunocytochemistry, and optimizing culture conditions by use of growth curve
      assays with a fractional factorial experimental design. Two cell viability
      assays, MTT and lactate dehydrogenase (LDH), and an assay measuring cytochrome
      P4501A (CYP1A) expression by quantitative PCR were optimized in the characterized
      cells. MTT and LDH assays confirmed cytotoxicity of perfluorooctanoic acid at 500
      MUM following 72 and 96 h exposures while CYP1A5 induction was detected after 72
      h exposure to 0.1-10 MUM benzo[a]pyrene. This research demonstrates the validity
      of in vitro toxicity testing in sea turtles and highlights the need to optimize
      mammalian assays to reptilian cells. 

PMID- 25384209
TI  - Asymmetric oxy-Michael addition to gamma-hydroxy-alpha,beta-unsaturated carbonyls
      using formaldehyde as an oxygen-centered nucleophile.
AB  - Formaldehyde was utilized as an oxygen-centered nucleophile in an asymmetric oxy
      Michael addition to gamma-hydroxy-alpha,beta-unsaturated carbonyl compounds using
      bifunctional organocatalysts through hemiacetal intermediates. The cyclic acetal
      product could be further transformed into beta-hydroxycarbonyl compounds, useful
      synthetic intermediates leading to various important target molecules. As such,
      this method is an example of a novel formal asymmetric hydration of alpha,beta
      unsaturated carbonyl compounds. 

PMID- 25384210
TI  - From chromium-chromium quintuple bonds to molecular squares and porous
      coordination polymers.
AB  - Reaction of the quintuply bonded chromium(I) dimer [ApCrCrAp] (Ap = sterically
      demanding 2-aminopyridinate) with pyrazine yields a chromium(II) complex with a
      eta(4):eta(4) face-on coordinated pyrazine dianion. Reaction with 4,4'
      bipyridine, on the other hand, completely cleaves the metal-metal bond, leading
      to a chromium(II)-based molecular square. XRD and magnetic measurements show
      ligand radical anions and a ferrimagnetic alignment of alternating metal and
      ligand magnetic moments. Controlled polymerization of the molecular square with
      pyrazine yields a porous coordination polymer featuring both reduced and
      nonreduced linkers. 

PMID- 25384211
TI  - Optimum insufflation capacity and peak cough flow in neuromuscular disorders.
AB  - RATIONALE: For patients with neuromuscular disorders, lung insufflation with
      positive pressure is an accepted technique to increase inspiratory volume over VC
      to improve peak cough flow (PCF). OBJECTIVES: The aim of the study was to
      determine the pressure or volume required to achieve the highest individual PCF.
      METHODS: In 40 patients dependent on noninvasive ventilation (VC, 16 +/- 11%
      predicted; age, 20 +/- 4 yr) and in 20 healthy control subjects, insufflation
      capacity (IC) was measured during titration from 10 to maximum 40 mbar using
      intermittent positive pressure breathing (IPPB) or the lung insufflation assist
      maneuver (LIAM) of the VENTIlogic LS ventilator. MEASUREMENTS AND MAIN RESULTS:
      IPPB or LIAM titration resulted in a pressure-volume curve with an estimated
      total compliance of 0.23 +/- 0.11 L/kPa in the patients and 1.0 +/- 0.3 L/kPa in
      the controls and a plateau for IC at pressures between 30 and 40 mbar. IPPB or
      LIAM improved VC from 451 +/- 229 ml to a maximum IC (ICmax) of 1,027 +/- 329 ml,
      and PCF improved from 109 +/- 45 to 202 +/- 62 L/min (P < 0.01 for all). The
      highest individual PCF was achieved with 27 +/- 6 mbar and an IC of 924 +/- 379
      ml, which was significantly below ICmax (P < 0.01). CONCLUSIONS: A submaximal
      insufflation is ideal for generating the best individual PCF even in patients
      with severely reduced compliance of the respiratory system. Optimum insufflation
      capacity can be achieved using IPPB or LIAM with moderate pressures. Both
      techniques are equally effective and considered safe.

PMID- 25384212
TI  - Follicular lymphoma: too many reminders for a memory B cell.
AB  - Memory B cells are a dynamic subset of the mature B cell population that in some
      cases can reenter germinal centers (GCs) in response to iterative infections.
      Such a reactivation can lead to accumulation of genetic lesions in these cells,
      potentially from repetitive activation of the B cell mutator enzyme AID. Normal
      memory B cells do not survive repeated reentries into GCs. In this issue,
      Sungalee et al. demonstrate that memory B cells harboring the oncogenic BCL2:IGH
      translocation, which results in constitutive BCL2 expression, survive multiple GC
      entries upon repetitive immunization. Through these multiple GC reentries, the
      hallmark BCL2:IGH translocation enables AID-induced hypermutation and propagates
      clonal evolution toward malignant follicular lymphoma. 

PMID- 25384213
TI  - Hyaluronan in cervical epithelia protects against infection-mediated preterm
      birth.
AB  - Increased synthesis of cervical hyaluronan (HA) from early to late pregnancy has
      long been proposed to play an essential role in disorganization of the collagen
      rich extracellular matrix to allow for maximal compliance and dilation of the
      cervix during the birth process. Here, we show that HA is not essential for
      increased cervical distensibility during late pregnancy. Rather, cervicovaginal
      HA plays an unanticipated important role in epithelial barrier protection of the
      lower reproductive tract. Specifically, HA depletion in the cervix and vagina
      resulted in inappropriate differentiation of epithelial cells, increased
      epithelial and mucosal permeability, and strikingly increased preterm birth rates
      in a mouse model of ascending vaginal infection. Collectively, these findings
      revealed that although HA is not obligatory for cervical compliance, it is
      crucial for maintaining an epithelial and mucosal barrier to limit pathogen
      infiltration of the lower reproductive tract during pregnancy and thereby is
      protective against infection-mediated preterm birth. 

PMID- 25384214
TI  - Tumor-associated neutrophils stimulate T cell responses in early-stage human lung
      cancer.
AB  - Infiltrating inflammatory cells are highly prevalent within the tumor
      microenvironment and mediate many processes associated with tumor progression;
      however, the contribution of specific populations remains unclear. For example,
      the nature and function of tumor-associated neutrophils (TANs) in the cancer
      microenvironment is largely unknown. The goal of this study was to provide a
      phenotypic and functional characterization of TANs in surgically resected lung
      cancer patients. We found that TANs constituted 5%-25% of cells isolated from the
      digested human lung tumors. Compared with blood neutrophils, TANs displayed an
      activated phenotype (CD62L(lo)CD54(hi)) with a distinct repertoire of chemokine
      receptors that included CCR5, CCR7, CXCR3, and CXCR4. TANs produced substantial
      quantities of the proinflammatory factors MCP-1, IL-8, MIP-1alpha, and IL-6, as
      well as the antiinflammatory IL-1R antagonist. Functionally, both TANs and
      neutrophils isolated from distant nonmalignant lung tissue were able to stimulate
      T cell proliferation and IFN-gamma release. Cross-talk between TANs and activated
      T cells led to substantial upregulation of CD54, CD86, OX40L, and 4-1BBL
      costimulatory molecules on the neutrophil surface, which bolstered T cell
      proliferation in a positive-feedback loop. Together our results demonstrate that
      in the earliest stages of lung cancer, TANs are not immunosuppressive, but rather
      stimulate T cell responses.

PMID- 25384215
TI  - NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer
      stem cells.
AB  - High aldehyde dehydrogenase (ALDH) activity is a marker commonly used to isolate
      stem cells, particularly breast cancer stem cells (CSCs). Here, we determined
      that ALDH1A1 activity is inhibited by acetylation of lysine 353 (K353) and that
      acetyltransferase P300/CBP-associated factor (PCAF) and deacetylase sirtuin 2
      (SIRT2) are responsible for regulating the acetylation state of ALDH1A1 K353.
      Evaluation of breast carcinoma tissues from patients revealed that cells with
      high ALDH1 activity have low ALDH1A1 acetylation and are capable of self-renewal.
      Acetylation of ALDH1A1 inhibited both the stem cell population and self-renewal
      properties in breast cancer. Moreover, NOTCH signaling activated ALDH1A1 through
      the induction of SIRT2, leading to ALDH1A1 deacetylation and enzymatic activation
      to promote breast CSCs. In breast cancer xenograft models, replacement of
      endogenous ALDH1A1 with an acetylation mimetic mutant inhibited tumorigenesis and
      tumor growth. Together, the results from our study reveal a function and
      mechanism of ALDH1A1 acetylation in regulating breast CSCs. 

PMID- 25384216
TI  - GP130 activation induces myeloma and collaborates with MYC.
AB  - Multiple myeloma (MM) is a plasma cell neoplasm that results from clonal
      expansion of an Ig-secreting terminally differentiated B cell. Advanced MM is
      characterized by tissue damage that involves bone, kidney, and other organs and
      is typically associated with recurrent genetic abnormalities. IL-6 signaling via
      the IL-6 signal transducer GP130 has been implicated as an important driver of MM
      pathogenesis. Here, we demonstrated that ectopic expression of constitutively
      active GP130 (L-GP130) in a murine retroviral transduction-transplantation model
      induces rapid MM development of high penetrance. L-GP130-expressing mice
      recapitulated all of the characteristics of human disease, including monoclonal
      gammopathy, BM infiltration with lytic bone lesions, and protein deposition in
      the kidney. Moreover, the disease was easily transplantable and allowed different
      therapeutic options to be evaluated in vitro and in vivo. Using this model, we
      determined that GP130 signaling collaborated with MYC to induce MM and was
      responsible and sufficient for directing the plasma cell phenotype. Accordingly,
      we identified Myc aberrations in the L-GP130 MM model. Evaluation of human MM
      samples revealed recurrent activation of STAT3, a downstream target of GP130
      signaling. Together, our results indicate that deregulated GP130 activity
      contributes to MM pathogenesis and that pathways downstream of GP130 activity
      have potential as therapeutic targets in MM. 

PMID- 25384217
TI  - Germinal center reentries of BCL2-overexpressing B cells drive follicular
      lymphoma progression.
AB  - It has recently been demonstrated that memory B cells can reenter and reengage
      germinal center (GC) reactions, opening the possibility that multi-hit
      lymphomagenesis gradually occurs throughout life during successive immunological
      challenges. Here, we investigated this scenario in follicular lymphoma (FL), an
      indolent GC-derived malignancy. We developed a mouse model that recapitulates the
      FL hallmark t(14;18) translocation, which results in constitutive activation of
      antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and
      applied a combination of molecular and immunofluorescence approaches to track
      normal and t(14;18)(+) memory B cells in human and BCL2-overexpressing B cells in
      murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC
      transits before acquiring FL-associated developmental arrest and presenting as GC
      B cells with constitutive activation-induced cytidine deaminase (AID) mutator
      activity. Moreover, multiple reentries into the GC were necessary for the
      progression to advanced precursor stages of FL. Together, our results demonstrate
      that protracted subversion of immune dynamics contributes to early dissemination
      and progression of t(14;18)(+) precursors and shapes the systemic presentation of
      FL patients.

PMID- 25384218
TI  - RASAL2 activates RAC1 to promote triple-negative breast cancer progression.
AB  - Patients with triple-negative breast cancer (TNBC) have a high incidence of early
      relapse and metastasis; however, the molecular basis for recurrence in these
      individuals remains poorly understood. Here, we demonstrate that RASAL2, which
      encodes a RAS-GTPase-activating protein (RAS-GAP), is a functional target of anti
      invasive microRNA-203 and is overexpressed in a subset of triple-negative or
      estrogen receptor-negative (ER-negative) breast tumors. As opposed to luminal B
      ER-positive breast cancers, in which RASAL2 has been shown to act as a RAS-GAP
      tumor suppressor, we found that RASAL2 is oncogenic in TNBC and drives
      mesenchymal invasion and metastasis. Moreover, high RASAL2 expression was
      predictive of poor disease outcomes in patients with TNBC. RASAL2 acted
      independently of its RAS-GAP catalytic activity in TNBC; however, RASAL2 promoted
      small GTPase RAC1 signaling, which promotes mesenchymal invasion, through binding
      and antagonizing the RAC1-GAP protein ARHGAP24. Together, these results indicate
      that activation of a RASAL2/ARHGAP24/RAC1 module contributes to TNBC
      tumorigenesis and identify a context-dependent role of RASAL2 in breast cancer. 

PMID- 25384220
TI  - Interstitial granulomatous dermatitis associated with gabapentin.

PMID- 25384221
TI  - Assessment of pruritus in patients with psoriasis and atopic dermatitis:
      subjective and objective tools.
AB  - Pruritus is a major symptom of skin disease. The quest to identify a valid and
      reliable method to assess this important symptom has led to the development of a
      myriad of measurement tools. Some clinical trials using subjective measurements
      of itch intensity have reported itch intensity levels in psoriasis that are close
      to severity levels found in atopic dermatitis. Although it is possible that we
      have previously underestimated the severity of pruritus in psoriasis, these
      unexpected findings prompted us to review and evaluate these subjective
      methodologies. We provide an overview of the current tools available to measure
      itch severity, including subjective rating scales and questionnaires and
      objective measures of scratch activity through videotape observation and wrist
      actigraphy. We discuss the advantages and limitations of these methods and
      encourage consideration of a novel objective method of evaluation. 

PMID- 25384219
TI  - IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion.
AB  - Human cytomegalovirus (HCMV) infection is the most common cause of congenital
      viral infections and a major source of morbidity and mortality after organ
      transplantation. NK cells are pivotal effector cells in the innate defense
      against CMV. Recently, hallmarks of adaptive responses, such as memory-like
      features, have been recognized in NK cells. HCMV infection elicits the expansion
      of an NK cell subset carrying an activating receptor heterodimer, comprising CD94
      and NKG2C (CD94/NKG2C), a response that resembles the clonal expansion of
      adaptive immune cells. Here, we determined that expansion of this NKG2C(+) subset
      and general NK cell recovery rely on signals derived from CD14(+) monocytes. In a
      coculture system, a subset of CD14(+) cells with inflammatory monocyte features
      produced IL-12 in response to HCMV-infected fibroblasts, and neutralization of IL
      12 in this model substantially reduced CD25 upregulation and NKG2C(+) subset
      expansion. Finally, blockade of CD94/NKG2C on NK cells or silencing of the
      cognate ligand HLA-E in infected fibroblasts greatly impaired expansion of
      NKG2C(+) NK cells. Together, our results reveal that IL-12, CD14(+) cells, and
      the CD94/NKG2C/HLA-E axis are critical for the expansion of NKG2C(+) NK cells in
      response to HCMV infection. Moreover, strategies targeting the NKG2C(+) NK cell
      subset have the potential to be exploited in NK cell-based intervention
      strategies against viral infections and cancer.

PMID- 25384222
TI  - Barrier creams: facts and controversies.
AB  - Barrier creams (BCs) represent devices aiming to protect the skin from contact
      with exogenous hazardous substances, especially under working conditions. By
      preventing penetration and absorption of contaminants, BCs are designed to reduce
      the risk of developing both irritant and allergic contact dermatitis. In fact,
      BCs should improve stratum corneum hydration as well as provide emolliency to
      maintain skin integrity and to restore and repair the epidermis barrier function.
      The formulation and ingredients of the available BCs vary widely, and thus the
      choice of a BC should depend on the kind of contaminants, occupational
      conditions, and skin dysfunction. Although BCs are commonly recommended to
      prevent occupational contact dermatitis, their real benefit remains
      controversial. The aims of this review are to help the choice of appropriate BCs
      and to analyze the actual effectiveness in maintaining an intact skin barrier,
      preventing contact dermatitis, and speeding up the healing of barrier-impaired
      skin.

PMID- 25384223
TI  - Adverse reactions to sunscreen agents: epidemiology, responsible irritants and
      allergens, clinical characteristics, and management.
AB  - Sunscreen is a key component in the preventive measures recommended by
      dermatologists and public health campaigns aimed at reducing sunburn, early skin
      aging, and skin cancer. To maximize compliance, adverse reactions to sunscreens
      should be minimized. Although inactive ingredients cause many of these reactions,
      it is important for dermatologists to be aware of reactions to active ultraviolet
      filters. There are approximately 120 chemicals that can function as ultraviolet
      (UV) filters. This review focuses on the 36 most common filters in commercial and
      historical use. Of these, 16 are approved for use by the US Food and Drug
      Administration. The benzophenones and dibenzoylmethanes are the most commonly
      implicated UV filters causing allergic and photoallergic contact dermatitis
      (PACD) reactions; benzophenone-3 is the leading allergen and photoallergen within
      this class. When clinically indicated, patch and photopatch testing should be
      performed to common UV filters.

PMID- 25384224
TI  - The utility of chamber scarification in the detection of allergic contact
      dermatitis to ophthalmic solutions.

PMID- 25384225
TI  - Posttraumatic eczema: a manifestation of the atopic diathesis?

PMID- 25384226
TI  - Prevalence and interest in the practice of scratch testing for contact urticaria:
      a survey of the American contact dermatitis society members.
AB  - BACKGROUND: Contact urticaria (CU) is the development of a wheal and flare on the
      skin after topical exposure to a particular chemical or compound. It can be
      diagnosed through a variety of techniques. Many chemicals that cause a type IV
      allergy can also cause CU. The incidence of CU to these chemicals is unknown.
      OBJECTIVE: The aim of this study was to evaluate the opinions of the American
      Contact Dermatitis Society members regarding CU and scratch testing. METHODS: We
      distributed an electronic survey to the American Contact Dermatitis Society
      members regarding observed prevalence of CU, frequency of scratch testing in
      clinical practice, and interest in learning about scratch testing in diagnosing
      CU and other skin contact conditions. RESULTS: We distributed 508 surveys and
      received 133 responses. Seventeen percent reported that CU was extremely rare,
      32% reported that CU was rare, and 38.9% reported that CU was infrequent.
      Alternatively, 10.7% believed that CU was common, and 1.5% believed that CU was
      extremely common. A minority, 19.1%, performed scratch testing on patients with
      suspected CU. Most respondents, 54.6%, were interested in learning about scratch
      testing. CONCLUSIONS: Additional education regarding scratch testing could
      increase comfort and use of scratch testing in clinical practice. Further studies
      are needed to evaluate the prevalence of CU in the general population and better
      guide the use of testing for dermatologic patients.

PMID- 25384227
TI  - A technique for identifying vicryl suture hypersensitivity.

PMID- 25384228
TI  - Patch testing in children from 2005 to 2012: results from the North American
      contact dermatitis group.
AB  - BACKGROUND: Allergic contact dermatitis is common in children. Epicutaneous patch
      testing is an important tool for identifying responsible allergens. OBJECTIVE:
      The objective of this study was to provide the patch test results from children
      (aged <=18 years) examined by the North American Contact Dermatitis Group from
      2005 to 2012. METHODS: This is a retrospective analysis of children patch-tested
      with the North American Contact Dermatitis Group 65- or 70-allergen series.
      Frequencies and counts were compared with previously published data (2001-2004)
      using chi statistics. CONCLUSIONS: A total of 883 children were tested during the
      study period. A percentage of 62.3% had >=1 positive patch test and 56.7% had >=1
      relevant positive patch test. Frequencies of positive patch test and relevant
      positive patch test reaction were highest with nickel sulfate (28.1/25.6), cobalt
      chloride (12.3/9.1), neomycin sulfate (7.1/6.6), balsam of Peru (5.7/5.5), and
      lanolin alcohol 50% petrolatum vehicle (5.5/5.1). The >=1 positive patch test and
      >=1 relevant positive patch test in the children did not differ significantly
      from adults (>=19 years) or from previously tested children (2001-2004). The
      percentage of clinically relevant positive patch tests for 27 allergens differed
      significantly between the children and adults. A total of 23.6% of children had a
      relevant positive reaction to at least 1 supplemental allergen. Differences in
      positive patch test and relevant positive patch test frequencies between children
      and adults as well as test periods confirm the importance of reporting periodic
      updates of patch testing in children to enhance clinicians' vigilance to
      clinically important allergens.

PMID- 25384229
TI  - Nickel and cobalt release from children's toys purchased in Denmark and the
      United States.
AB  - BACKGROUND: Nickel is the most common allergen detected by patch testing in
      children. There is an increasing number of cases in children who have not had
      exposure to piercing. Although the clinical relevance of nickel patch test
      reactions in children is sometimes uncertain, continued vigilance to identify new
      sources of nickel exposure in this age group is important. Recent case reports
      have described allergic nickel contact dermatitis in children following exposure
      to toys, but the magnitude of this problem is unknown. OBJECTIVE: The aim of this
      study was to evaluate nickel and cobalt release from children's toys. METHODS: We
      purchased 212 toys in 18 different retail and online stores in the United States
      and Denmark. Nickel and cobalt release was tested using the dimethylglyoxime and
      cobalt screening spot tests. RESULTS: A total of 73 toys (34.4%) released nickel,
      and none released cobalt. CONCLUSIONS: Toys are a commonly overlooked source of
      nickel exposure and sensitization. Therefore, dermatologists, allergists, and
      pediatricians should consider the role of toys in their evaluation of children
      with dermatitis, and the parents of children with positive nickel patch test
      reactions should be told that toys may release nickel and be a potential chemical
      source in the manifestation of allergic contact dermatitis.

PMID- 25384230
TI  - Two new emergent interleukins in allergic contact dermatitis.

PMID- 25384231
TI  - Successful rapid desensitization for allergic dermatitis to cattle.

PMID- 25384233
TI  - Genistein alleviates beta-amyloid-induced inflammatory damage through regulating
      Toll-like receptor 4/nuclear factor kappaB.
AB  - Genistein (GEN), a major soybean isoflavone (SIF), might possess neuroprotective
      properties through its anti-inflammatory activity. We hypothesized that GEN could
      prevent the inflammatory damage detected in C6 cells induced by beta-amyloid
      peptides 25-35 (Abeta25-35). Accordingly, we evaluated the inflammatory damage
      induced by Abeta25-35 and the protective effect of GEN against Abeta25-35 in C6
      cells. In our study, the C6 glial cells (rats glioma cell lines) were
      preincubated with or without GEN for 2 h following incubation with Abeta25-35 for
      another 24 h. Then, methylthiazolyl tetrazolium (MTT) assay was used to assess
      the cell viability. Immunofluorescence staining was used to identify the C6
      cells. Inflammatory factors tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-1beta were analyzed by using enzyme-linked immunosorbent assay (ELISA).
      Western blot analysis and reverse transcription-polymerase chain reaction
      analysis were performed to assess the expression of Toll-like receptors 4 (TLR4),
      inhibitor of kappaB-alpha (IkappaB-alpha). The current results showed that GEN
      could alleviate Abeta25-35-induced cell apoptosis and prevent Abeta25-35-induced
      TNF-alpha and IL-1beta release from C6 cells. In addition, GEN prevented Abeta25
      35-induced upregulation of the gene and protein expression of TLR4, and GEN
      significantly upregulated the expression of IkappaB-alpha in C6 cells damaged by
      Abeta25-35. These results suggest that GEN can alleviate the inflammatory stress
      caused by Abeta25-35 treatment, which might be associated with the
      neuroprotective effect of GEN regulating the TLR4/NFkappaB signaling pathway.

PMID- 25384234
TI  - Triazene as a powerful tool for solid-phase derivatization of phenylalanine
      containing peptides: zygosporamide analogues as a proof of concept.
AB  - A novel method for the synthesis of para-substituted phenylalanine containing
      cyclic peptides is described. The main features of this strategy are the coupling
      of phenylalanine to the solid support through its side chain via a triazene
      linkage, on-resin cyclization of the peptide chain, cleavage of the cyclic
      peptide from the resin under mild acidic conditions and further transformation of
      the resulting diazonium salt. The usefulness of this approach is exemplified by
      the solid-phase synthesis of some derivatives of the naturally occurring cyclic
      depsipeptide zygosporamide. 

PMID- 25384235
TI  - Functional fixedness: The functional significance of delayed disengagement based
      on attention set.
AB  - During search, the disengagement of attention is automatically delayed when a
      fixated but task-irrelevant object shares features of the search target. We
      examined whether delayed disengagement based on top-down attention set is
      potentially functional, resulting in additional processing of the fixated item.
      To accomplish this, we adapted the oculomotor disengagement paradigm.
      Participants saccaded to a peripheral object of a particular color and responded
      to the identity of the letter within it. To initiate search participants made a
      saccade away from an always irrelevant object at the center of the screen that
      matched or mismatched the target's color and contained a letter that was
      congruent or incongruent with the target letter. We found that delayed
      disengagement based on attention set was associated with deeper processing of the
      center item: a congruency effect between the center letter and peripheral target
      letter was only observed when the center object's color matched participants'
      attention set. Results are consistent with the proposal that delayed
      disengagement based on attention set is functionally significant, automatically
      encouraging deeper levels of processing of target-like objects that fall within
      the focus of attention.

PMID- 25384236
TI  - Humans don't time subsecond intervals like a stopwatch.
AB  - Many activities require the ability to estimate intervals of time in an accurate
      and flexible manner. A traditional and popular account suggests that humans
      possess a kind of internal stopwatch that can be started, paused, and stopped at
      will. Here we test this idea by measuring variable performance errors in 3
      experiments. Participants had to compare the total time accumulated during 1 to 3
      short target intervals with a single standard interval. With 2 or more target
      intervals, participants had to pause, but not reset, their putative internal
      stopwatches. By establishing baseline performance at 2 different standard
      durations and extrapolating based on Weber's law, we were able to estimate how
      much performance should have deteriorated when target segments contained breaks.
      The decrement in performance we observed far exceeded the stopwatch prediction,
      and also exceeded the simulated predictions of a modified stopwatch with a
      slowing pacemaker. The data thus favor either a counter that cannot be paused
      during subsecond durations or alternative models of subsecond interval duration
      discrimination that do not posit a count-based metric for time. We discuss
      several possible strategies that participants might have implemented to apply
      such clocks in the split-interval task.

PMID- 25384238
TI  - Parafoveal preview benefit is modulated by the precision of skilled readers'
      lexical representations.
AB  - In skilled reading, the processing of an upcoming word often begins in the
      parafovea, that is, before the word is fixated. This study investigated whether
      the extraction and use of multiple sources of information about an upcoming word
      depends on reading skill. The eye movements of 107 skilled adult readers,
      assessed on measures of reading and spelling ability, were recorded. The gaze
      contingent boundary paradigm was used to manipulate the preview of a target
      word's identity and length in sentences with low- or high-frequency pretarget
      words. Across all first-pass reading measures, superior reading ability was
      associated with a larger preview benefit, but only among readers with high
      spelling ability, suggesting that the orthographic precision of a reader's stored
      lexical representations influences the extraction of parafoveal information.
      There was also evidence that the highly skilled reader/spellers' parafoveal
      processing advantage derived partly from their efficient foveal processing.
      Finally, in first fixations on the target, increased preview benefit for highly
      skilled reader/spellers was restricted to accurate length previews, suggesting
      that readers with precise lexical representations use upcoming word length in
      combination with parafoveal orthographic information to narrow down potential
      lexical candidates. The implications of these results for computational models of
      eye movements are discussed.

PMID- 25384237
TI  - The visible ground surface as a reference frame for scaling binocular depth of a
      target in midair.
AB  - The natural ground surface carries texture information that extends continuously
      from one's feet to the horizon, providing a rich depth resource for accurately
      locating an object resting on it. Here, we showed that the ground surface's role
      as a reference frame also aids in locating a target suspended in midair based on
      relative binocular disparity. Using real world setup in our experiments, we first
      found that a suspended target is more accurately localized when the ground
      surface is visible and the observer views the scene binocularly. In addition, the
      increased accuracy occurs only when the scene is viewed for 5 s rather than 0.15
      s, suggesting that the binocular depth process takes time. Second, we found that
      manipulation of the configurations of the texture-gradient and/or linear
      perspective cues on the visible ground surface affects the perceived distance of
      the suspended target in midair. Third, we found that a suspended target is more
      accurately localized against a ground texture surface than a ceiling texture
      surface. This suggests that our visual system uses the ground surface as the
      preferred reference frame to scale the distance of a suspended target according
      to its relative binocular disparity.

PMID- 25384239
TI  - The role of auditory feedback in speech and song.
AB  - When singing a melody or producing sentences, we take for granted the fact that
      the sounds we create (auditory feedback) match the intended consequences of our
      actions. The importance of these perception/action matches to production is
      illustrated by the detrimental effects of altered auditory feedback (AAF).
      Previous research in the domain of music has shown that when AAF leads to
      asynchronies between perception and action, timing of production is disrupted but
      accuracy of sequencing is not. On the other hand, AAF manipulations of pitch
      disrupt sequencing but not timing. Such dissociative effects, as well as other
      findings, suggest that sensitivity to AAF may be based on hierarchical
      organization of sequences. In the current research we examined whether similar
      effects are found for the production of speech, for which syllables rather than
      pitches may constitute content units. In the first experiment, participants
      either sang melodies or spoke sequences of nonsense syllables. In the second
      experiment, the tasks were combined such that participants sang syllable
      sequences. Production in both experiments was accompanied by either normal,
      asynchronous, or content altered auditory feedback. Across experiments, effects
      of AAF on the accuracy of sequencing were similar in speaking and singing tasks,
      and in all cases reflected the dissociative effects described earlier. For timing
      of production, however, previous results were only found when participants sang
      sequences that did not have varying syllabic content. These results suggest that
      sensitivity to timing exists at multiple hierarchical levels, particularly at the
      syllable and phonetic levels.

PMID- 25384240
TI  - Discovery heralds new approach to the treatment of cystic fibrosis.

PMID- 25384241
TI  - Ionic liquid dependence of triplet-sensitized photon upconversion.
AB  - Photon upconversion (UC) is a technology used to convert wasted lower energy
      photons to usable higher energy photons. Triplet-sensitized UC based on the
      triplet-triplet annihilation (TTA) of organic molecules has recently received
      attention because of its applicability to noncoherent sunlight. Among the various
      media proposed for this UC, ionic liquids (ILs) are practically advantageous
      because of their nonvolatility and nonflammability. However, from previous
      studies, the efficiency of UC (PhiUC) has been found to depend on the ILs
      employed. In this article, systematic investigations were carried out on samples
      made using more than 10 kinds of ILs, all of which were purified before sample
      fabrication to enhance data reliability. Several clear tendencies were found, and
      they were all related to the viscosity of the ILs. We also found that the
      magnitude of their solvatochromic shifts did not correlate to these trends. These
      results show that the dynamic aspects of the molecules influence the kinetics
      that govern the magnitude of PhiUC. Along with related discussions and
      interpretations, these results should provide a guideline toward increasing the
      PhiUC. 

PMID- 25384242
TI  - Mechanical grinding of a single-crystalline metal-organic framework triggered
      emission with tunable violet-to-orange luminescence.
AB  - A metal-organic framework (MOF) featuring intriguing Borromean entanglement
      exhibits a unique mechanochromic luminescence with on-off switching. The
      concomitant excitation wavelength-dependent emission behavior can be utilized to
      tune the emission color from violet to orange. 

PMID- 25384244
TI  - Maternal and fetal blood levels of S100 and ischaemia modified albumin in term
      intrauterine growth restricted fetuses with abnormal umbilical artery Doppler
      values.
AB  - The purpose of this study was to investigate whether levels of fetal hypoxia
      markers, S100 and ischaemia modified albumin (IMA) change in cases of
      intrauterine growth restriction (IUGR). This case-control study included 15
      intrauterine growth restricted fetuses and 20 age-matched controls. During
      delivery of the fetuses, cord blood and maternal blood S100 and IMA levels were
      studied. The fetal weight and umbilical cord pH values of IUGR fetuses were
      significantly lower than the control group. The mean maternal and umbilical cord
      blood values of S100 and IMA were similar in the two groups. IMA levels in cord
      blood of the IUGR group were significantly higher than maternal levels, whereas
      umbilical and maternal levels of IMA did not differ among control cases. In cases
      without brain sparing effect in Doppler ultrasonography, umbilical cord S100 and
      IMA levels do not change significantly in IUGR when compared with appropriate-for
      gestational-age (AGA) fetuses. 

PMID- 25384243
TI  - Grease matrix as a versatile carrier of proteins for serial crystallography.
AB  - Serial femtosecond X-ray crystallography (SFX) has revolutionized atomic
      resolution structural investigation by expanding applicability to micrometer
      sized protein crystals, even at room temperature, and by enabling dynamics
      studies. However, reliable crystal-carrying media for SFX are lacking. Here we
      introduce a grease-matrix carrier for protein microcrystals and obtain the
      structures of lysozyme, glucose isomerase, thaumatin and fatty acid-binding
      protein type 3 under ambient conditions at a resolution of or finer than 2 A. 

PMID- 25384245
TI  - Authenticity analysis of pear juice employing chromatographic fingerprinting.
AB  - Pear juice is predominately composed of carbohydrates/polyols (>95% of the total
      soluble solids), making it susceptible to adulteration by the addition of less
      expensive commercial sweeteners. In this research, the major carbohydrate and
      polyol (fructose, glucose, sucrose, and sorbitol) content of 32 pure pear juices
      representing five world producing regions and three years of production was
      determined. Additionally, methods employing oligosaccharide profiling to detect
      the debasing of these samples with four commercial sweeteners (HFCS 55 and 90,
      TIS, and HIS) were developed using capillary gas chromatography with flame
      ionization detection (CGC-FID) and high-performance liquid chromatography with
      pulsed amperometric detection (HPAE-PAD). Detection limits for the four
      commercial sweeteners ranged from 0.5 to 5.0% (v/v). In addition, the developed
      CGC-FID method could be used to (a) detect the addition of pear to apple juice
      via arbutin detection and (b) determine if a pear juice was produced using
      enzymatic liquefaction via the presence of O-beta-d-glucopyranosyl-(1->4)-d
      glucopyranose (cellobiose), all within a single chromatographic analysis. 

PMID- 25384246
TI  - Palladium-Catalyzed Anti-Markovnikov Oxidation of Allylic Amides to Protected
      beta-Amino Aldehydes.
AB  - A general method for the preparation of N-protected beta-amino aldehydes from
      allylic amines or linear allylic alcohols is described. Here the Pd(II)-catalyzed
      oxidation of N-protected allylic amines with benzoquinone is achieved in tBuOH
      under ambient conditions with excellent selectivity toward the anti-Markovnikov
      aldehyde products and full retention of configuration at the allylic carbon. The
      method shows a wide substrate scope and is tolerant of a range of protecting
      groups. Furthermore, beta-amino aldehydes can be obtained directly from protected
      allylic alcohols via palladium-catalyzed autotandem reactions, and the
      application of this method to the synthesis of beta-peptide aldehydes is
      described. From a mechanistic perspective, we demonstrate that tBuOH acts as a
      nucleophile in the reaction and that the initially formed tert-butyl ether
      undergoes spontaneous loss of isobutene to yield the aldehyde product.
      Furthermore, tBuOH can be used stoichiometrically, thereby broadening the solvent
      scope of the reaction. Primary and secondary alcohols do not undergo elimination,
      allowing the isolation of acetals, which subsequently can be hydrolyzed to their
      corresponding aldehyde products. 

PMID- 25384247
TI  - Seimisochromenes A and B: two new dihydroisochromenes from the endophytic fungus,
      Seimatosporium sp.
AB  - Two new dihydroisochromenes, named seimisochromenes A and B (1 and 2), were
      isolated from an endophytic fungus, Seimatosporium sp. The structures of
      seimisochromenes A and B have been determined from 1D ((1)H and (13)C NMR
      spectra) and 2D (COSY, HMQC, HMBC, and NOESY) NMR experiments. 

PMID- 25384248
TI  - Facile dispersion and control of internal structure in lyotropic liquid
      crystalline particles by auxiliary solvent evaporation.
AB  - Submicron sized, structured lyotropic liquid crystalline (LLC) particles, so
      called hexosomes and cubosomes, are generally obtained by high energy input
      dispersion methods, notably ultrasonication and high-pressure emulsification. We
      present a method to obtain dispersions of such LLC particles with a significantly
      reduced energy input, by evaporation of an auxiliary volatile solvent immiscible
      with water, e.g. cyclohexane or limonene. The inner structure of the particles
      can be precisely controlled by the addition of a nonvolatile oil, such as alpha
      tocopherol or tetradecane consistently with bulk phase diagrams,. Two different
      lyotropic surfactants were employed, industrial grade monolinoleine (MLO) and soy
      bean phosphatidylcholine (PC). The lyotropic surfactant and oil phase modifier
      were first dissolved in the volatile solvent to give a liquid reverse micellar
      (L2) phase, which requires significantly less energy input to be dispersed in an
      aqueous solution of secondary emulsifier compared to the corresponding gel-like
      bulk mesophase. The auxiliary volatile solvent was then removed from the emulsion
      by evaporation at room temperature, yielding LLC particles of the desired inner
      structure, Pn3m, H2, or Fd3m. The obtained particles were characterized by small
      angle X-ray scattering (SAXS), dynamic light scattering (DLS), and cryogenic
      transmission electron microscopy (cryo-TEM). Our method enables fine-tuning of
      the final particle size through the volatile-to-nonvolatile volume ratio and
      processing conditions. 

PMID- 25384249
TI  - Discovery of a bacterial 5-methylcytosine deaminase.
AB  - 5-Methylcytosine is found in all domains of life, but the bacterial cytosine
      deaminase from Escherichia coli (CodA) will not accept 5-methylcytosine as a
      substrate. Since significant amounts of 5-methylcytosine are produced in both
      prokaryotes and eukaryotes, this compound must eventually be catabolized and the
      fragments recycled by enzymes that have yet to be identified. We therefore
      initiated a comprehensive phylogenetic screen for enzymes that may be capable of
      deaminating 5-methylcytosine to thymine. From a systematic analysis of sequence
      homologues of CodA from thousands of bacterial species, we identified putative
      cytosine deaminases where a "discriminating" residue in the active site,
      corresponding to Asp-314 in CodA from E. coli, was no longer conserved.
      Representative examples from Klebsiella pneumoniae (locus tag: Kpn00632),
      Rhodobacter sphaeroides (locus tag: Rsp0341), and Corynebacterium glutamicum
      (locus tag: NCgl0075) were demonstrated to efficiently deaminate 5-methylcytosine
      to thymine with values of kcat/Km of 1.4 * 10(5), 2.9 * 10(4), and 1.1 * 10(3) M(
      1) s(-1), respectively. These three enzymes also catalyze the deamination of 5
      fluorocytosine to 5-fluorouracil with values of kcat/Km of 1.2 * 10(5), 6.8 *
      10(4), and 2.0 * 10(2) M(-1) s(-1), respectively. The three-dimensional structure
      of Kpn00632 was determined by X-ray diffraction methods with 5-methylcytosine
      (PDB id: 4R85 ), 5-fluorocytosine (PDB id: 4R88 ), and phosphonocytosine (PDB id:
      4R7W ) bound in the active site. When thymine auxotrophs of E. coli express these
      enzymes, they are capable of growth in media lacking thymine when supplemented
      with 5-methylcytosine. Expression of these enzymes in E. coli is toxic in the
      presence of 5-fluorocytosine, due to the efficient transformation to 5
      fluorouracil. 

PMID- 25384250
TI  - Salt stress-induced protein pattern associated with photosynthetic parameters and
      andrographolide content in Andrographis paniculata Nees.
AB  - Andrographis paniculata is a multifunctional medicinal plant and a potent source
      of bioactive compounds. Impact of environmental stresses such as salinity on
      protein diversification, as well as the consequent changes in the photosynthetic
      parameters and andrographolide content (AG) of the herb, has not yet been
      thoroughly investigated. The present study showed that the salinity affects the
      protein pattern, and subsequently, it decreased the photosynthetic parameters,
      protein content, total dry weight, and total crude extract. Exceptionally, the AG
      content was increased (p <= 0.01). Moreover, it was noticed that the salinity at
      12 dS m(-1) led to the maximum increase in AG content in all accessions.
      Interestingly, the leaf protein analysis revealed that the two polymorphic
      protein bands as low- and medium-sized of 17 and 45 kDa acted as the activator
      agents for the photosynthetic parameters and AG content. Protein sequencing and
      proteomic analysis can be conducted based on the present findings in the future. 

PMID- 25384251
TI  - Functionalization of monolithic and porous three-dimensional graphene by one-step
      chitosan electrodeposition for enzymatic biosensor.
AB  - Biological modification of monolithic and porous 3D graphene is of great
      significance for extending its application in fabricating highly sensitive
      biosensors. The present work reports on the first biofunctionalization of
      monolithic and freestanding 3D graphene foam for one-step preparation of
      reagentless enzymatic biosensors by controllable chitosan (CS) electrodeposition
      technology. Using a homogeneous three-component electrodeposition solution
      containing a ferrocene (Fc) grafted CS hybrid (Fc-CS), glucose oxidase (GOD), and
      single-walled carbon nanotubes (SWNTs), a homogeneous biocomposite film of Fc
      CS/SWNTs/GOD was immobilized on the surface of 3D graphene foam by one-step
      electrodeposition. The Fc groups grafted on chitosan can be stably immobilized on
      the 3D graphene surface and keep their original electrochemical activity. The
      SWNTs doped into the Fc-CS matrix act as a nanowire to facilitate electron
      transfer and improve the conductivity of the biocomposite film. Combined with the
      extraordinary properties of 3D graphene foam including large active surface area,
      high conductivity, and fast mass transport dynamics, the 3D graphene based
      enzymatic biosensor achieved a large linear range (5.0 MUM to 19.8 mM), a low
      detection limit (1.2 MUM), and rapid response (reaching the 95% steady-state
      response within 8 s) for reagentless detection of glucose in the phosphate buffer
      solution. 

PMID- 25384252
TI  - The business side of telemedicine.

PMID- 25384253
TI  - Utility and effectiveness of a remote telepresence robotic system in nursing
      education in a simulated care environment.
AB  - BACKGROUND: There is a growing shortage of nursing graduates and faculty to
      prepare students for careers in nursing. One way to ameliorate this paradigm is
      to integrate technology such as a remote presence robot (RPR) in both clinical
      and educational settings. MATERIALS AND METHODS: The InTouch Health (Santa
      Barbara, CA) RP-7, an RPR, was deployed in a simulated, multigenerational home
      where nursing students and faculty interact in a variety of activities. Seventy
      students and five faculty members were instructed by a remotely located
      instructor who controlled the RP-7 from a distant site. Students and faculty,
      using questionnaires, provided feedback on the didactic interaction. RESULTS: Of
      the 70 student participants, 56 (80%) responded, and faculty and clinical staff
      were 100% compliant, resulting in 69 total respondents. Using Krippendorf's
      themes of (1) usefulness, (2) acceptability, and (3) impact, the data indicated
      the following. The majority of the students (89%) had no previous experience with
      the RPR, but the majority (75%) felt that the RPR was a good faculty extender.
      The students were initially evenly split on first exposure in (a) a positive
      experience, (b) a negative experience, or (c) a mixed experience. Although there
      were some technical challenges in operations, these were not deemed significant;
      nevertheless, they must be addressed. CONCLUSIONS: The results of this study
      support the use of RPRs as faculty extenders to facilitate course quality
      assurance when the lead faculty is not on site. Both faculty and students
      perceive this type of technology as a potential faculty extender, but both
      faculty and students need preparation for the experience.

PMID- 25384254
TI  - ATA clinical guidelines for telepathology.

PMID- 25384255
TI  - Development and evaluation of a mobile application for personal lifestyle check
      up and improvement.
AB  - OBJECTIVE: This study aimed (1) to help individuals analyze their own health
      status by checking their lifestyle, (2) to develop a user-friendly mobile
      application that offered prescriptions for lifestyle improvement, and (3) to
      examine whether the developed application had positive effects on users.
      MATERIALS AND METHODS: In order to develop a lifestyle analysis engine that would
      operate in an Android((r)) (Google, Mountain View, CA)-based mobile application,
      survey data on health awareness behaviors of 25,124 participants from the 2009
      Korean National Health and Nutrition Examination Survey (KNHANES) were analyzed.
      Additionally, in order for the users to be aware of their lifestyles and explore
      the effects of the developed mobile application on lifestyle management and
      improvement, an additional survey of the lifestyle awareness and levels of
      motivation for lifestyle improvement of 152 users was conducted. RESULTS: The
      differences between lifestyles before and after using the application were
      examined. A paired t test was used for questions regarding (1) the level of
      motivation to improve lifestyles and (2) changes in lifestyle. The lifestyle
      score was lower after using the program than before using it. Conversely, the
      level of motivation to improve lifestyle was greater after the program than
      before it. Both results were statistically significant. CONCLUSIONS: By using the
      KNHANES, this study developed a mobile application that compared the quantified
      lifestyles of individuals and enabled individuals to check easily their health
      statuses, whenever and wherever necessary. The program developed in this study
      contributed to motivating individuals to be aware of and to improve their
      lifestyles.

PMID- 25384257
TI  - Cation-alkane interaction.
AB  - Ab initio computations, up to CCSD(T)/CBS on model systems, and MP2/cc-pVTZ and
      DFT calculations are performed on cation-alkane and cation-alkene complexes,
      cation = Li(+), Na(+), Be(2+), Mg(2+), Ca(2+), Cu(+) and Zn(2+); alkane =
      C(n)H2(n+2) (n = 1-10) and C6H12; and alkene = C2H4 and C6H6. Density functional
      theory-symmetry adapted perturbation theory (DFT-SAPT) calculations reveal that
      the cation-alkane interactions are predominantly constituted of induction
      component. The dramatic modulation of the strength of their interaction and the
      topological features obtained from atoms in molecules (AIM) analysis are
      consistent with the characteristics of a typical noncovalent interaction. In
      contrast to many of the conventional noncovalent interactions, cation-alkane
      interactions are substantially strong and are comparable in strength to the well
      studied cation-pi interactions.

PMID- 25384256
TI  - Discovery of desketoraloxifene analogues as inhibitors of mammalian, Pseudomonas
      aeruginosa, and NAPE phospholipase D enzymes.
AB  - Phospholipase D (PLD) hydrolyses cellular lipids to produce the important lipid
      second messenger phosphatidic acid. A PLD enzyme expressed by Pseudomonas
      aeruginosa (PldA) has been shown to be important in bacterial infection, and NAPE
      PLD has emerged as being key in the synthesis of endocannabinoids. In order to
      better understand the biology and therapeutic potential of these less explored
      PLD enzymes, small molecule tools are required. Selective estrogen receptor
      modulators (SERMs) have been previously shown to inhibit mammalian PLD (PLD1 and
      PLD2). By targeted screening of a library of SERM analogues, additional parallel
      synthesis, and evaluation in multiple PLD assays, we discovered a novel
      desketoraloxifene-based scaffold that inhibited not only the two mammalian PLDs
      but also structurally divergent PldA and NAPE-PLD. This finding represents an
      important first step toward the development of small molecules possessing
      universal inhibition of divergent PLD enzymes to advance the field. 

PMID- 25384258
TI  - Analysis of PAEs in semen of infertile men.
AB  - OBJECTIVES: Phthalates are environmental chemicals with reproductive toxicity and
      estrogenic effects in animals. They are of increasing concern to human health.
      AIM: To determine whether phthalate levels in semen were associated with
      infertility. METHODS: Using semen samples from 107 infertile and 94 fertile men,
      the presence and quantity of five phthalate esters were measured using high
      performance liquid chromatography (HPLC). Using data collected from
      questionnaires and clinical examinations, the correlation between phthalate
      exposure and semen quality was analyzed. RESULTS: The cumulative levels of the
      measured phthalate esters were significantly higher in the infertility group
      compared to the control group (P<0.05). Concentrations of the five phthalate
      esters in men varied by age with older men showing higher cumulative levels.
      CONCLUSIONS: The presence of phthalates may contribute to male infertility in our
      study population.

PMID- 25384260
TI  - Impact of rehabilitation on self-concept following traumatic brain injury: An
      exploratory systematic review of intervention methodology and efficacy.
AB  - To date, reviews of rehabilitation efficacy after traumatic brain injury (TBI)
      have overlooked the impact on sense of self, focusing instead on functional
      impairment and psychological distress. The present review sought to address this
      gap by critically appraising the methodology and efficacy of intervention studies
      that assess changes in self-concept. A systematic search of PsycINFO, Medline,
      CINAHL and PubMed was conducted from inception to September 2013 to identify
      studies reporting pre- and post-intervention changes on validated measures of
      self-esteem or self-concept in adults with TBI. Methodological quality of
      randomised controlled trials (RCTs) was examined using the Physiotherapy Evidence
      Database (PEDro) scale. A total of 17 studies (10 RCTs, 4 non-RCT group studies,
      3 case studies) was identified, which examined the impact of psychotherapy,
      family-based support, cognitive rehabilitation or activity-based interventions on
      self-concept. The findings on the efficacy of these interventions were mixed,
      with only 10 studies showing some evidence of improvement in self-concept based
      on within-group or pre-post comparisons. Such findings highlight the need for
      greater focus on the impact of rehabilitation on self-understanding with improved
      assessment and intervention methodology. We draw upon theories of identity
      reconstruction and highlight implications for the design and evaluation of
      identity-oriented interventions that can supplement existing rehabilitation
      programmes for people with TBI. 

PMID- 25384259
TI  - Effects of cooking fuel smoke on respiratory symptoms and lung function in semi
      rural women in Cameroon.
AB  - BACKGROUND: Indoor air pollution is a major health problem in the developing
      world. In sub-Saharan Africa more than 90% of people rely on biomass to meet
      their domestic energy demands. Pollution from biomass fuel ranks 10th among
      preventable risk factors contributing to the global burden of diseases.
      OBJECTIVES: The present study aimed to determine the prevalence of respiratory
      symptoms and the factors associated with reduced lung function in a population of
      women exposed to cooking fuel smoke. METHODS: A cross-sectional study was
      conducted in a semi-rural area in Cameroon. We compared forced respiratory volume
      between women using wood (n = 145) and women using alternative sources of energy
      (n = 155) for cooking. RESULTS: Chronic bronchitis was found in 7.6% of the wood
      smoke group and 0.6% in the alternative fuels group. We observed two cases of
      airflow obstruction in the wood smoke group. Factors associated with lung
      function impairment were chronic bronchitis, use of wood as cooking fuel, age,
      and height. CONCLUSION: Respiratory symptoms and reduced lung function are more
      pronounced among women using wood as cooking fuel. Improved stoves technology
      should be developed to reduce the effects of wood smoke on respiratory health.

PMID- 25384261
TI  - Rates of psychotropic medication use reported by borderline patients and axis II
      comparison subjects over 16 years of prospective follow-up.
AB  - The purpose of this study was to assess the classes and types of psychotropic
      medication reported by borderline patients and axis II comparison subjects over
      16 years of prospective follow-up. Medication use was assessed at baseline using
      a semistructured interview of proven reliability and validity as well as its
      follow-up analog at 8 contiguous 2-year follow-up periods. A significantly higher
      percentage of borderline patients than axis II comparison subjects reported
      taking an antidepressant, an anxiolytic, an antipsychotic, and a mood stabilizer
      over time. They also reported more commonly taking 7 of the 10 more specific
      types of medication studied (ie, all but tricyclic antidepressants, monoamine
      oxidase inhibitor antidepressants, and atypical antipsychotics). The rates over
      time of taking antipsychotics and mood stabilizers were stable, whereas there was
      a significant decline in the rates of antidepressants and anxiolytics from
      baseline to 8-year follow-up (but not from 8- to 16-year follow-up) reported by
      those in both study groups. In terms of specific medications, rates of atypical
      antidepressants and anticonvulsants were the most stable. In contrast,
      nonbenzodiazepine anxiolytics declined the most steadily over time, whereas rates
      of atypical antipsychotics increased significantly over the 16 years of
      prospective follow-up. Taken together, the results of this study suggest that a
      substantial percentage of borderline patients continue to use the major classes
      of medication over time. They also suggest that the declining rates of use tend
      to stabilize less than a decade after index admission. 

PMID- 25384262
TI  - Are corporations people too? The neural correlates of moral judgments about
      companies and individuals.
AB  - To investigate whether the legal concept of "corporate personhood" mirrors an
      inherent similarity in the neural processing of the actions of corporations and
      people, we measured brain responses to vignettes about corporations and people
      while participants underwent functional magnetic resonance imaging. We found that
      anti-social actions of corporations elicited more intense negative emotions and
      that pro-social actions of people elicited more intense positive emotions.
      However, the networks underlying the moral decisions about corporations and
      people are strikingly similar, including regions of the canonical theory of mind
      network. In analyzing the activity in these networks, we found differences in the
      emotional processing of these two types of vignettes: neutral actions of
      corporations showed neural correlates that more closely resembled negative
      actions than positive actions. Collectively, these findings indicate that our
      brains understand and analyze the actions of corporations and people very
      similarly, with a small emotional bias against corporations. 

PMID- 25384264
TI  - Self-association of amphotericin B: spontaneous formation of molecular structures
      responsible for the toxic side effects of the antibiotic.
AB  - Amphotericin B (AmB) is a lifesaving antibiotic used to treat deep-seated mycotic
      infections. Both the pharmaceutical activity and highly toxic side effects of the
      drug rely on its interaction with biomembranes, which is governed by the
      molecular organization of AmB. In the present work, we present a detailed
      analysis of self-assembly of AmB molecules in different environments, interesting
      from the physiological standpoint, based on molecular spectroscopy techniques:
      electronic absorption, circular dichroism, steady state and time-resolved
      fluorescence and molecular dynamic calculations. The results show that, in the
      water medium, AmB self-associates to dimeric structures, referred to as
      "parallel" and "antiparallel". AmB dimers can further assemble into tetramers
      which can play a role of transmembrane ion channels, affecting
      electrophysiological homeostasis of a living cell. Understanding structural
      determinants of self-assembly of AmB opens a way to engineering preparations of
      the drug which retain pharmaceutical effectiveness under reduced toxicity. 

PMID- 25384265
TI  - Amniotic fluid phthalate levels and male fetal gonad function.
AB  - BACKGROUND: Prenatal exposure to phthalates may pose a threat to human male
      reproduction. However, additional knowledge about the in vivo effect in humans is
      needed, and reported associations with genital abnormalities are inconclusive. We
      aimed to study prenatal di(2-ethylhexyl) phthalate (DEHP) and diisononyl
      phthalate (DiNP) exposure in relation to cryptorchidism, hypospadias, and human
      fetal Leydig cell function. METHODS: We studied 270 cryptorchidism cases, 75
      hypospadias cases, and 300 controls. Second-trimester amniotic fluid samples were
      available from a Danish pregnancy-screening biobank (n = 25,105) covering 1980
      1996. We assayed metabolites of DEHP and DiNP (n = 645) and steroid hormones (n =
      545) by mass spectrometry. We assayed insulin-like factor 3 by immunoassay (n =
      475) and analyzed data using linear or logistic regression. RESULTS: Mono(2-ethyl
      5-carboxypentyl) phthalate (5cx-MEPP, DEHP metabolite) was not consistently
      associated with cryptorchidism or hypospadias. However, we observed an 18% higher
      (95% confidence interval [CI] = 5%-33%) testosterone level, and a 41% lower (-56%
      to -21%) insulin-like factor 3 level in the highest 5cx-MEPP tertile compared
      with the lowest. Mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP, DiNP
      metabolite) showed elevated odds ratio point estimates for having cryptorchidism
      (odds ratio = 1.28 [95% CI = 0.80 to 2.01]) and hypospadias (1.69 [0.78 to
      3.67]), but was not consistently associated with the steroid hormones or insulin
      like factor 3. CONCLUSIONS: Data on the DEHP metabolite indicate possible
      interference with human male fetal gonadal function. Considering the DiNP
      metabolite, we cannot exclude (nor statistically confirm) an association with
      hypospadias and, less strongly, with cryptorchidism.

PMID- 25384266
TI  - New tyrosinase inhibitors from Paecilomyces gunnii.
AB  - Through screening 50 strains of entomopathogenic fungi and rescreening of 7
      strains of Paecilomyces gunnii, a methanol extract of liquid-cultivated mycelia
      of P. gunnii was found to have the strongest tyrosinase inhibitory activity.
      Preparative high-speed counter-current chromatography (HSCCC) guided by high
      performance liquid chromatography (HPLC)-electrospray ionization (ESI)-high
      resolution mass spectrometry (HRMS) was employed for the isolation and
      purification of the active components, and three new compounds with half
      inhibition concentration (IC50) of 0.11, 0.17, and 0.14 mM against diphenolase
      were obtained from the extract, respectively. Their chemical structures were
      identified by HRMS, one- and two-dimensional nuclear magnetic resonance (2D NMR)
      spectroscopy as paecilomycones A, B, and C. Structure and activity studies showed
      that the tyrosinase inhibition activities are positively related to the number of
      hydroxyl groups on the paecilomycones. 

PMID- 25384267
TI  - The role of multiple wildlife hosts in the persistence and spread of bovine
      tuberculosis in New Zealand.
AB  - AIM: To explore how the inclusion of multi-host dynamics affects the predicted
      prevalence of bovine tuberculosis (TB) in possums and other host species
      following the current best practice for control of TB in large difficult and
      remote areas, to identify which host species are responsible for changes in
      predicted prevalence, and whether TB can persist in possum-free host communities.
      METHODS: Multi-host TB models were constructed, comprising three host species
      with density-dependent population growth, density-dependent disease transmission
      and susceptible and infected classes. Models were parameterised for two case
      studies of current concern in New Zealand, namely chronic TB persistence in a
      possum-deer-pig complex in extensive forest, and in a possum-pig-ferret complex
      in unforested semi-arid shrub and grasslands. Persistence of TB in the face of
      best practice possum control was evaluated from model simulations, and the
      contribution of different hosts to persistence of TB was assessed by removing
      each host species in turn from the simulations. A sensitivity test explored how
      different parameter values affected modelled persistence of TB. RESULTS: The
      forest multi-host model-predicted amplification of TB prevalence due to the
      presence of pigs. The presence of pigs and/or deer did not jeopardise the success
      of best practice possum control in eradicating TB from the system, as pigs and
      deer are effectively end-hosts for TB. Sensitivity analyses indicated these
      interpretations were robust to uncertainty in model parameter values. The
      grassland system model predicted that the multi-host species complex could
      potentially lead to failure of eradication of TB under possum-only control, due
      to TB persisting in ferret and pig populations in the absence of possum hosts
      through reciprocal scavenging, resulting in spillback transmission to possums
      once their populations had started to recover from control. CONCLUSIONS: With
      respect to management of TB, for modelled forest habitats, 15 years of effective
      possum control was predicted to eradicate TB from the possum-deer-pig host
      community, indicating the current focus on possum-only control is appropriate for
      such areas. For grassland model systems, TB was predicted to persist in the
      ferret-pig host complex in the absence of possums, potentially jeopardising the
      effectiveness of possum-only control programmes. However this outcome depended on
      the occurrence and rate of pigs acquiring TB from ferrets, which is unknown. Thus
      some estimation of this transmission parameter is required to enable managers to
      assess if multi-host disease dynamics are important for their TB control
      programmes.

PMID- 25384268
TI  - Dual amplified electrochemical immunosensor for highly sensitive detection of
      Pantoea stewartii sbusp. stewartii.
AB  - Accurate and highly sensitive detection of Pantoea stewartii sbusp. stewartii
      NCPPB 449 (PSS) is urgently required for international shipments due to
      tremendous agricultural economic losses. Herein, a dual amplified electrochemical
      sandwich immunosensor for PSS detection was developed, utilizing the good
      specificity and low cost of electrochemical immunoassay, the favorable
      conductivity and large specific surface area of gold nanoparticles (Au NPs), and
      the excellent catalytic ability of and horseradish peroxidase (HRP). A linear
      curve between current response and PSS concentration was established, and the
      limit of detection (LOD) was 7.8 * 10(3) cfu/mL, which is 20 times lower than
      that for conventional enzyme-linked immunosorbent assay (ELISA). This strategy is
      a useful approach for the highly sensitive detection of plant pathogenic
      bacterium. 

PMID- 25384277
TI  - Dual-energy CT for imaging of pulmonary hypertension: challenges and
      opportunities.
AB  - Computed tomography (CT) is routinely used in the evaluation of patients with
      pulmonary hypertension (PH) to assess vascular anatomy and parenchymal
      morphology. The introduction of dual-energy CT (DECT) enables additional
      qualitative and quantitative insights into pulmonary hemodynamics and the extent
      and variability of parenchymal enhancement. Lung perfusion assessed at pulmonary
      blood volume imaging correlates well with findings at scintigraphy, and pulmonary
      blood volume defects seen in pulmonary embolism studies infer occlusive disease
      with increased risk of right heart dysfunction. Similarly, perfusion
      inhomogeneities seen in patients with PH closely reflect mosaic lung changes and
      may be useful for severity assessment and prognostication. The use of DECT may
      increase detection of peripheral thromboembolic disease, which is of particular
      prognostic importance in patients with chronic thromboembolic PH with
      microvascular involvement. Other DECT applications for imaging of PH include low
      kilovoltage images with greater inherent iodine conspicuity and iodine-selective
      color-coded maps of vascular perfusion (both of which can improve visualization
      of vascular enhancement), virtual nonenhanced imaging (which better depicts
      vascular calcification), and, potentially, ventricular perfusion maps (to assess
      myocardial ischemia). In addition, quantitative assessment of central vascular
      and parenchymal enhancement can be used to evaluate pulmonary hemodynamics in
      patients with PH. The current status and potential advantages and limitations of
      DECT for imaging of PH are reviewed, and current evidence is supplemented with
      data from a tertiary referral center for PH.

PMID- 25384269
TI  - An evolved Mxe GyrA intein for enhanced production of fusion proteins.
AB  - Expressing antibodies as fusions to the non-self-cleaving Mxe GyrA intein enables
      site-specific, carboxy-terminal chemical modification of the antibodies by
      expressed protein ligation (EPL). Bacterial antibody-intein fusion protein
      expression platforms typically yield insoluble inclusion bodies that require
      refolding to obtain active antibody-intein fusion proteins. Previously, we
      demonstrated that it was possible to employ yeast surface display to express
      properly folded single-chain antibody (scFv)-intein fusions, therefore permitting
      the direct small-scale chemical functionalization of scFvs. Here, directed
      evolution of the Mxe GyrA intein was performed to improve both the display and
      secretion levels of scFv-intein fusion proteins from yeast. The engineered intein
      was shown to increase the yeast display levels of eight different scFvs by up to
      3-fold. Additionally, scFv- and green fluorescent protein (GFP)-intein fusion
      proteins can be secreted from yeast, and while fusion of the scFvs to the wild
      type intein resulted in low expression levels, the engineered intein increased
      scFv-intein production levels by up to 30-fold. The secreted scFv- and GFP-intein
      fusion proteins retained their respective binding and fluorescent activities, and
      upon intein release, EPL resulted in carboxy-terminal azide functionalization of
      the target proteins. The azide-functionalized scFvs and GFP were subsequently
      employed in a copper-free, strain-promoted click reaction to site-specifically
      immobilize the proteins on surfaces, and it was demonstrated that the
      functionalized, immobilized scFvs retained their antigen binding specificity.
      Taken together, the evolved yeast intein platform provides a robust alternative
      to bacterial intein expression systems. 

PMID- 25384278
TI  - Invited commentary on "Dual-energy CT for imaging of pulmonary hypertension".

PMID- 25384279
TI  - Multidetector CT evaluation of airway stents: what the radiologist should know.
AB  - Airway stents are increasingly used to treat symptomatic patients with
      obstructive tracheobronchial diseases who are not amenable to surgical resection
      or who have poor performance status, precluding them from resection. The most
      common conditions that are treated with tracheobronchial stents are primary lung
      cancer and metastatic disease. However, stents have also been used to treat
      patients with airway stenosis related to a variety of benign conditions, such as
      tracheobronchomalacia, relapsing polychondritis, postintubation tracheal
      stenosis, postoperative anastomotic stenosis, and granulomatous diseases.
      Additionally, airway stents can be used as a barrier method in the management of
      esophagorespiratory fistulas. Many types of stents are available from different
      manufacturers. Principally, they are classified as silicone; covered and
      uncovered metal; or hybrid, which are made of silicone and reinforced by metal
      rings. The advantages and disadvantages of each type of airway stent are
      carefully considered when choosing the most appropriate stent for each patient.
      Multidetector computed tomography plays an important role in determining the
      cause and assessing the location and extent of airway obstruction. Moreover, it
      is very accurate in its depiction of complications after airway stent placement.

PMID- 25384280
TI  - To do or not to do: axillary nodal evaluation after ACOSOG Z0011 Trial.
AB  - Methods of axillary evaluation in invasive breast cancer continue to evolve. The
      recent American College of Surgeons Oncology Group Z0011 Trial is a prospective,
      randomized, multicenter trial that compared the survival and locoregional
      recurrence rates after complete axillary lymph node dissection (ALND) versus
      sentinel node biopsy (SNB) alone in women with a positive sentinel node in an
      effort to avoid the complications associated with ALND. As the results of this
      trial are implemented clinically, affecting surgical management of axillary
      metastatic disease, radiologists may need to redefine their role in the
      preoperative assessment of the axilla. Before the Z0011 trial, breast imagers
      worked to identify axillary metastases preoperatively, allowing appropriate
      patients to proceed directly to ALND and avoiding the need for SNB. However, the
      Z0011 trial concluded that ALND may not be necessary in women with metastatic
      axillary disease who meet the trial criteria. In the Z0011 trial, after 6 years
      of median follow-up there was no difference in either locoregional recurrence or
      survival among the women who underwent SNB alone compared with those who
      underwent ALND, suggesting that ALND is unnecessary in a subset of women with a
      positive node at SNB. These results raise questions about how aggressively
      radiologists should pursue percutaneous sampling of axillary nodes, as some
      practitioners conclude that, in an otherwise eligible woman, positive results
      from imaging-guided percutaneous biopsy preclude a Z0011 trial-directed pathway.
      Debate about the best way to implement the results of the Z0011 trial into daily
      clinical practice exists. It is important for breast imagers to work closely with
      breast surgeons to provide the most appropriate treatment course for each
      patient.

PMID- 25384281
TI  - Resident and fellow education feature: US evaluation of axillary lymph nodes.

PMID- 25384282
TI  - Techniques for creating video content for radiology education.
AB  - Video podcasts, or vodcasts, are an innovative tool for teaching and learning
      that allow the efficient distribution of tutorials, lectures, and other
      educational content. Certain types of content lend themselves to presentation in
      a video format. For example, vodcasts are well suited to teaching radiologic
      procedures. Vodcasts might also be quite useful in demonstrating the use of an
      audience response system and how one system differs from another, providing
      background content before an active-learning session, comparing magnetic
      resonance imaging pulse sequences, and teaching valuable interpersonal skills
      such as how to deliver bad news to a patient or how to maintain professionalism
      in the work environment. The authors present a step-by-step text-and-video
      tutorial on how to create, edit, and export vodcasts using a variety of software
      tools, describing both the "how" and the "why" of creating vodcasts. Interested
      readers are encouraged to examine both the print and online versions of this
      article to gain a more comprehensive knowledge of the ideas presented by the
      authors. Online supplemental material is available for this article.

PMID- 25384283
TI  - Current concepts in imaging evaluation of penetrating transmediastinal injury.
AB  - Penetrating transmediastinal injuries (TMIs) are injuries that traverse the
      mediastinum. These injuries are most commonly caused by firearms and knives. The
      investigation and management algorithms for TMI have undergone changes in recent
      years due to increasing evidence that computed tomography (CT) in useful in the
      evaluation of hemodynamically stable TMI patients. Initial investigation of TMI
      patients depends on the question of hemodynamic stability. In unstable patients,
      imaging (if any) should be limited to bedside radiography and focused
      ultrasonography. In hemodynamically stable patients in whom a mediastinal
      trajectory of injury is suspected, the primary imaging modality after radiography
      should be multidetector CT. CT is invaluable in the assessment of TMI due to its
      capacity to depict the injury track as well as demonstrate both direct and
      indirect signs of organ injury. On the basis of the suspected trajectory and
      specific findings, radiologists can play an essential role in determining future
      patient management and investigations for each mediastinal organ, thereby
      expediting appropriate investigation and treatment and avoiding unnecessary and
      sometimes invasive tests or surgery. The authors provide an up-to-date and
      evidence-based approach for the management of hemodynamically unstable and stable
      patients with suspected TMI, discuss management algorithms and CT protocols, and
      highlight common and uncommon imaging findings and diagnostic pitfalls associated
      with vascular, cardiac, esophageal, tracheobronchial, pleural, and pulmonary
      injuries. Online supplemental material is available for this article.

PMID- 25384284
TI  - Multidetector CT of blunt cervical spine trauma in adults.
AB  - A number of new developments in cervical spine imaging have transpired since the
      introduction of 64-section computed tomographic (CT) scanners in 2004. An
      increasing body of evidence favors the use of multidetector CT as a stand-alone
      screening test for excluding cervical injuries in polytrauma patients with
      obtundation. A new grading scale that is based on CT and magnetic resonance (MR)
      imaging findings, the cervical spine Subaxial Injury Classification and Scoring
      (SLIC) system, is gaining acceptance among spine surgeons. Radiographic
      measurements described for the evaluation of craniocervical distraction injuries
      are now being reevaluated with the use of multidetector CT. Although most
      patients with blunt trauma are now treated nonsurgically, evolution in the
      understanding of spinal stability, as well as the development of new surgical
      techniques and hardware, has driven management strategies that are increasingly
      favorable toward surgical intervention. It is therefore essential that
      radiologists recognize findings that distinguish injuries with ligamentous
      instability or a high likelihood of nonfusion that require surgical stabilization
      from those that are classically stable and can be treated with a collar or halo
      vest alone. The purpose of this article is to review the spectrum of cervical
      spine injuries, from the craniocervical junction through the subaxial spine, and
      present the most widely used grading systems for each injury type.

PMID- 25384286
TI  - Congratulations to the 2014 RSNA Outstanding Educator: Paula J. Woodward, MD.

PMID- 25384287
TI  - Practice corner: Retrieval practice makes perfect.

PMID- 25384288
TI  - Insights into digital tomosynthesis of interstitial lung disease.

PMID- 25384289
TI  - Imaging findings of successful and failed fundoplication.
AB  - Postoperative imaging findings contribute to the diagnosis of successful and
      failed fundoplication procedures. Gastroesophageal reflux disease, a common
      illness in the United States, is primarily treated medically but may require
      surgery if there are persistent symptoms or reflux complications despite medical
      treatment. Laparoscopic Nissen fundoplication has become the most used and
      successful surgical antireflux procedure since its introduction in 1991.
      Radiologists should understand the anatomy of the esophagogastric junction,
      antireflux and esophageal protective mechanisms, and preoperative radiologic
      findings that contribute to selection of the surgical technique, as well as the
      most commonly used antireflux operations and their indications. Barium
      examination and computed tomography of the thorax and abdomen play an important
      role in the follow-up of patients with gastric fundoplication, including
      evaluation of surgical effectiveness and detection and characterization of
      postoperative complications. Failed fundoplications are classified into six
      types: tight Nissen, incompetent repair, disruption of the wrap, stomach slippage
      above the diaphragm, slipped Nissen, and transdiaphragmatic wrap herniation.
      Classification is based on radiologic visualization of the obstructed esophageal
      lumen, recurrence of gastroesophageal reflux, integrity and location of the
      gastric wrap, stomach slippage, and recurrence of hiatal hernia. Imaging findings
      are useful in detecting complications, providing anatomic information to identify
      the cause of surgical failure, and selecting appropriate medical or surgical
      management.

PMID- 25384291
TI  - Invited commentary on "CT colonography with computer-aided detection: recognizing
      the causes of false-positive reader results".

PMID- 25384290
TI  - CT colonography with computer-aided detection: recognizing the causes of false
      positive reader results.
AB  - Computed tomography (CT) colonography is a screening modality used to detect
      colonic polyps before they progress to colorectal cancer. Computer-aided
      detection (CAD) is designed to decrease errors of detection by finding and
      displaying polyp candidates for evaluation by the reader. CT colonography CAD
      false-positive results are common and have numerous causes. The relative
      frequency of CAD false-positive results and their effect on reader performance on
      the basis of a 19-reader, 100-case trial shows that the vast majority of CAD
      false-positive results were dismissed by readers. Many CAD false-positive results
      are easily disregarded, including those that result from coarse mucosa,
      reconstruction, peristalsis, motion, streak artifacts, diverticulum, rectal
      tubes, and lipomas. CAD false-positive results caused by haustral folds,
      extracolonic candidates, diminutive lesions (<6 mm), anal papillae, internal
      hemorrhoids, varices, extrinsic compression, and flexural pseudotumors are almost
      always recognized and disregarded. The ileocecal valve and tagged stool are
      common sources of CAD false-positive results associated with reader false
      positive results. Nondismissable CAD soft-tissue polyp candidates larger than 6
      mm are another common cause of reader false-positive results that may lead to
      further evaluation with follow-up CT colonography or optical colonoscopy.
      Strategies for correctly evaluating CAD polyp candidates are important to avoid
      pitfalls from common sources of CAD false-positive results.

PMID- 25384293
TI  - AIRP best cases in radiologic-pathologic correlation: gastroblastoma: a rare
      biphasic gastric tumor.

PMID- 25384292
TI  - Update on the role of imaging in management of metastatic colorectal cancer.
AB  - Evolution in the treatment of metastatic colorectal cancer (mCRC) has led to
      significant improvement in the survival of these patients. Surgery is useful in
      patients with resectable disease. Liver-directed therapies such as hepatic
      arterial infusion, transarterial radio- and chemoembolization, and percutaneous
      ablation are sometimes used by oncologists when the liver is the only site of
      metastatic disease. Unresectable mCRC is typically treated with systemic
      chemotherapy. First-line systemic chemotherapeutic regimens for mCRC are FOLFOX
      (combination of 5-fluorouracil/leucovorin [5-FU/LV] and oxaliplatin) and FOLFIRI
      (combination of 5-FU/LV and irinotecan) combined with molecular targeted drugs.
      Molecular targeted therapies that are effective in treating mCRC include
      antiangiogenic agents such as bevacizumab-an antibody against vascular
      endothelial growth factor-and antibodies directed against epidermal growth factor
      receptor (EGFR). EGFR-directed antibodies such as cetuximab and panitumumab have
      been shown to produce activity only in wild-type KRAS tumors. Imaging modalities
      such as multidetector computed tomography (CT), magnetic resonance imaging, and
      positron emission tomography/CT play a major role in the selection of appropriate
      treatment strategies. Assessment of treatment response in patients who undergo
      liver-directed and systemic therapy requires imaging at regular intervals. Recent
      studies have shown that alternative treatment response criteria may be more
      predictive of pathologic response in mCRC than conventional criteria such as
      Response Evaluation Criteria in Solid Tumors. Awareness of unusual response
      patterns, as well as of complications and toxicities, is helpful in guiding
      patient management.

PMID- 25384294
TI  - From the radiologic pathology archives: gastrointestinal lymphoma: radiologic and
      pathologic findings.
AB  - Gastrointestinal (GI) lymphoma encompasses a heterogeneous group of neoplasms
      that have a common lymphoid origin but variable pathologic and imaging features.
      Extranodal marginal zone B-cell lymphoma (ENMZL) and diffuse large B-cell
      lymphoma (DLBCL) are the most common. ENMZL usually occurs in the stomach, where
      it is associated with chronic infection by Helicobacter pylori, and is typically
      a superficial spreading lesion that causes mucosal nodularity or ulceration and
      mild wall thickening. DLBCL may arise de novo or from transformation of ENMZL or
      other low-grade lymphomas. This form of lymphoma produces extensive wall
      thickening or a bulky mass, but obstruction is uncommon. Mantle cell lymphoma is
      the classic cause of lymphomatous polyposis, but multiple polyps or nodules can
      also be seen with ENMZL and follicular lymphoma. Burkitt lymphoma is usually
      characterized by an ileocecal mass or wall thickening in the terminal ileum in
      young children, often in the setting of widespread disease. Primary GI Hodgkin
      lymphoma, which is rare, may be manifested by a variety of findings, though
      stenosis is more common than with non-Hodgkin lymphoma. Enteropathy-associated T
      cell lymphoma is frequently associated with celiac disease and is characterized
      by wall thickening, ulceration, and even perforation of the jejunum. Accurate
      radiologic diagnosis of GI lymphoma requires a multifactorial approach based on
      the clinical findings, site of involvement, imaging findings, and associated
      complications.

PMID- 25384295
TI  - Diagnostic imaging of benign and malignant osseous tumors of the fingers.
AB  - Primary lesions of the tubular bones of the digits are not uncommon, and the vast
      majority of these lesions are benign. Benign intramedullary lesions such as
      enchondromas are frequently discovered incidentally, unless they are associated
      with a pathologic fracture. Expansile lesions or lesions that are pedunculated
      and protrude from the cortex may manifest with pain and functional deficits from
      local inflammatory reactions. Systemic disorders such as sarcoidosis and local
      soft-tissue lesions with involvement of adjacent bone may mimic primary
      phalangeal bone tumors. Primary or secondary malignant lesions of the phalanges,
      most commonly chondrosarcomas, are extremely rare, and their characterization may
      require the use of multiple modalities, including radiography, computed
      tomography, and magnetic resonance imaging. Although ultrasonography is extremely
      useful in the evaluation of soft-tissue lesions of the hand, its role in the
      evaluation of osseous lesions is limited. The authors describe the imaging
      features of the most common benign osseous and chondral lesions of the fingers,
      including enchondromas, cystic lesions, and osteochondromas. In addition, they
      discuss malignant entities that may occur in the fingers (eg, chondrosarcomas and
      metastatic lesions) and commonly encountered mimics of primary osseous lesions
      (eg, glomus tumors, intraosseous epidermal inclusion cysts, infectious entities,
      and manifestations of systemic diseases). They also discuss the advantages and
      disadvantages of the most commonly used imaging modalities in differentiating
      benign from malignant lesions.

PMID- 25384296
TI  - Hand infections: anatomy, types and spread of infection, imaging findings, and
      treatment options.
AB  - Infections of the hand are common, particularly in immunocompromised patients,
      and can lead to significant morbidity, including amputation, if not treated
      properly. Hand infection can spread far and wide from the original site of
      inoculation through interconnections between the synovium-lined and nonsynovial
      potential spaces. Because surgery is the mainstay of treatment, knowledge of the
      pertinent anatomy is imperative for accurately describing the presence, location,
      and extent of infection. The authors review the pertinent anatomy of the spaces
      of the hand and describe different types of infection-including cellulitis,
      necrotizing fasciitis, paronychia, felon, pyogenic flexor tenosynovitis, deep
      space infections, septic arthritis, and osteomyelitis-and common causative
      organisms of these infections. They also describe various modes of spread; the
      common radiologic appearances of hand infections, with emphasis on findings at
      magnetic resonance imaging and ultrasonography; and the role of radiology in the
      management of these infections, along with a brief overview of treatment options.

PMID- 25384297
TI  - Malignant involvement of the peripheral nervous system in patients with cancer:
      multimodality imaging and pathologic correlation.
AB  - The clinical and imaging evaluation of peripheral neuropathies in patients with
      cancer is challenging. It is critically important to differentiate malignant
      invasion of the peripheral nervous system from nonmalignant causes, such as
      radiation-induced neuritis, neuropathy associated with chemotherapy, and
      inflammatory neuropathies. Contrast material-enhanced magnetic resonance (MR)
      imaging is the initial noninvasive test of choice; however, interpretation can be
      challenging when the anatomic features are distorted by prior surgery, radiation,
      or both. Fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission
      tomography (PET)/computed tomography (CT) is an imaging adjunct to MR imaging
      that is particularly helpful for evaluating peripheral nerves because the
      metabolic activity depicted with (18)F-FDG PET/CT helps differentiate malignant
      from benign disease and assists in making certain management decisions. For
      example, sites of high (18)F-FDG activity in a peripheral nerve can be targeted
      to increase the diagnostic yield of a biopsy because malignant involvement of
      peripheral nerves can be patchy. Of note, (18)F-FDG PET/CT can show clinically
      unsuspected metastases elsewhere in the body. If cancer is found, (18)F-FDG
      PET/CT allows excellent assessment of treatment response. (18)F-FDG PET/CT is
      also useful in evaluating primary nerve sheath tumors in that such tumors with
      low metabolic activity on FDG PET/CT images are unlikely to be malignant,
      although the specificity is limited. It is essential to have a good understanding
      of the imaging characteristics of benign and malignant causes of peripheral
      neuropathy if (18)F-FDG PET/CT is to be used effectively for accurate diagnosis.

PMID- 25384298
TI  - More than just Langerhans cell histiocytosis: a radiologic review of histiocytic
      disorders.
AB  - Although Langerhans cell histiocytosis (LCH) is a familiar entity to most
      radiologists and to pediatric radiologists in particular, it is but one of a
      group of disorders caused by the overproduction of histiocytes, a subtype of
      white blood cells. Other less familiar diseases in this category are Erdheim
      Chester disease (ECD), juvenile xanthogranuloma (JXG), Rosai-Dorfman disease
      (RDD), and hemophagocytic lymphohistiocytosis (HLH). This review describes the
      classification system, clinical manifestations, and pathophysiology of each
      disease, with particular attention to differential radiographic findings,
      including typical locations of involvement and varying appearances at
      radiography, computed tomography, magnetic resonance imaging, ultrasonography,
      and nuclear medicine imaging. Although LCH has a wide variety of manifestations
      and appearances, classic imaging findings include vertebra plana, skull lesions
      with a beveled edge, the "floating tooth" sign, bizarre lung cysts, and an absent
      posterior pituitary bright spot with infundibular thickening. The classic imaging
      findings of ECD are a perirenal rind of soft tissue and patchy long bone
      osteosclerosis. RDD has more nonspecific imaging findings, including
      lymphadenopathy (most commonly cervical) and intracranial lesions. Imaging
      findings in HLH are broad, with the most common abnormalities being
      hepatosplenomegaly, cerebral volume loss, and periventricular white matter
      abnormalities. JXG can manifest at imaging, but radiology does not play a major
      role in diagnosis. Familiarity with these disorders and their associated imaging
      findings facilitates correct and timely diagnosis. Imaging also features
      prominently in the assessment of treatment response.

PMID- 25384299
TI  - Posttransplantation lymphoproliferative disease: proposed imaging classification.
AB  - Posttransplantation lymphoproliferative disease (PTLD) is the second most common
      tumor in adult transplant recipients. Most cases of PTLD are attributed to
      Epstein-Barr virus. Decreased levels of immunosurveillance against this tumor
      virus as a result of immunosuppressive regimens are thought to account for most
      cases of PTLD. Histologically, PTLD ranges from relatively benign lymphoid
      hyperplasia to poorly differentiated lymphoma, and tissue sampling is required to
      establish the subtype. The frequency of PTLD varies depending on the type of
      allograft and immunosuppressive regimen. PTLD has a bimodal manifestation, with
      most cases occurring within the first year after transplantation and a second
      peak occurring 4-5 years after transplantation. Patients are often asymptomatic
      or present with nonspecific symptoms, and a mass visible at imaging may be the
      first clue to the diagnosis. Imaging plays an important role in identifying the
      presence of disease, guiding tissue sampling, and evaluating response to
      treatment. The appearance of PTLD at imaging can vary. It may be nodal or
      extranodal. Extranodal disease may involve the gastrointestinal tract, solid
      organs, or central nervous system. Solid organ lesions may be solitary or
      multiple, infiltrate beyond the organ margins, and obstruct organ outflow.
      Suggestive imaging findings should prompt tissue sampling, because knowledge of
      the PTLD subtype is imperative for appropriate treatment. Treatment options
      include reducing immunosuppression, chemotherapy, radiation therapy, and surgical
      resection of isolated lesions.

PMID- 25384300
TI  - Review of ovarian tumors in children and adolescents: radiologic-pathologic
      correlation.
AB  - The incidence, histologic distribution, and clinical manifestations of ovarian
      tumors in the pediatric population are distinct from those in adults. Although
      ovarian neoplasms in childhood and adolescence are rare, the diagnosis should be
      considered in young girls with abdominal pain and a palpable mass. Differential
      diagnosis in children and adolescents with ovarian tumors should be conducted on
      the basis of unique clinical manifestations, elevated serum tumor marker levels,
      and distinctive imaging findings. Although the clinical manifestations are
      nonspecific and may overlap, they may assist in diagnosis of some types of
      ovarian tumors. Children who present with a palpable mass or symptoms of
      precocious puberty have a high likelihood of malignancy. Many ovarian tumors are
      associated with abnormal hormonal activity and/or abnormal sexual development.
      Elevated levels of serum tumor markers, including alpha-fetoprotein, the beta
      subunit of human chorionic gonadotropin, and CA-125, raise concern for ovarian
      malignancies. However, negative tumor markers do not exclude the possibility of
      malignancy. Identification of imaging features at ultrasonography, computed
      tomography, and magnetic resonance imaging can help differentiate benign from
      malignant ovarian tumors and, in turn, plays a crucial role in determining
      treatment options. At imaging, malignant ovarian tumors usually appear
      predominantly solid or heterogeneous and are larger than benign tumors. Because
      surgery is the primary treatment for ovarian tumors, ovarian salvage with
      fertility preservation and use of a minimally invasive surgical technique are
      important in children and adolescents.

PMID- 25384301
TI  - AIRP best cases in radiologic-pathologic correlation: prenatal and postmortem
      imaging of a complex cloacal malformation.

PMID- 25384302
TI  - Reducing barriers to timely MR imaging scheduling.
AB  - Scheduling a magnetic resonance (MR) imaging study at the authors' large health
      system in 2011 required considerable preparation before an appointment time was
      given to a patient. Difficulties in promptly scheduling appointments resulted
      from the varying time required for examinations, depending on the requested
      protocol, availability of appropriate MR imaging equipment, examination timing,
      prior insurance authorization verification, and proper patient screening. These
      factors contributed to a backlog of patients to schedule that regularly exceeded
      300. A multidisciplinary process-improvement team was assembled to improve the
      turnaround time for scheduling an outpatient MR imaging examination (the interval
      between the time when the order was received and the time when the patient was
      informed about the MR imaging appointment). Process improvements targeted by the
      team included protocol turnaround time, schedule standardization, schedule
      intervals, examination timing, service standards, and scheduling redesign. Using
      lean methods and multiple plan-do-check-act cycles, the time to schedule an
      outpatient MR imaging examination improved from 117 hours to 33 hours, a 72%
      reduction, during the 9-month study period in 2011-2012. The number of patients
      in the scheduling queue was reduced by 90%. Overall MR imaging examinations
      within the specific patient population studied increased from 773 patient studies
      during the first month of intervention to 1444 studies the following month and
      averaged over 1279 patient studies per month throughout the study.

PMID- 25384304
TI  - Diarylethene based fluorescent switchable probes for the detection of amyloid
      beta pathology in Alzheimer's disease.
AB  - Two fluorescent switchable diarylethene derivatives which exhibit high affinity
      for amyloid-beta aggregates with the increase of fluorescence intensity were
      reported. Moreover, the probes show excellent photochromic and anti
      photobleaching properties both in vitro and in vivo. 

PMID- 25384305
TI  - Examining the decomposed brain.
AB  - Examination of the decomposed brain is a largely neglected area of forensic
      neuropathology. However, careful examination often yields valuable information
      that may assist in criminal proceedings. Decomposition encompasses the processes
      of autolysis, putrefaction, and decay. Most decomposed brains will be affected by
      both autolysis and putrefaction, resulting in a brain that may, at one end of the
      spectrum, be almost normal or, at the other end, pulpified, depending on the
      conditions in which the body remained after death and the postmortem interval.
      Naked eye examination may detect areas of hemorrhage and also guides appropriate
      sampling for histology. Histological appearances are often better than what would
      be predicted from the state of the brain. Histology often confirms macroscopic
      abnormalities and may also reveal other features such as ischemic injury. Silver
      staining demonstrates neuritic plaques, and immunocytochemistry for beta-amyloid
      precursor protein and other molecules produces results comparable with those seen
      in well-preserved fixed brains. The usefulness of information derived from the
      examination of the decomposed brain in criminal proceedings is illustrated with 6
      case reports drawn from the author's own practice. 

PMID- 25384306
TI  - Case report of a fatal intoxication by Nucynta.
AB  - Tapentadol (Nucynta) is a centrally acting opioid analgesic prescribed for the
      treatment of moderate to severe acute pain. Its efficacy is believed to be due to
      MU-opioid receptor agonist activity and inhibition of norepinephrine reuptake
      resulting in increased norepinephrine concentrations. There is only one other
      case in the literature relating to the toxicity of this agent or report of a
      fatality. This case report documents a case in which tapentadol was identified as
      the cause of death. The tapentadol concentration found in the heart blood
      submitted in this case was more than 20 times the upper limit of the therapeutic
      range. Possible mechanisms of death include respiratory depression, central
      nervous system depression, and serotonin syndrome. Based on the scene
      investigation and autopsy findings in this case, the medical examiner determined
      that the cause of death was narcotic (Nucynta) intoxication and the manner of
      death was undetermined. 

PMID- 25384310
TI  - Occult intraorbital conjunctival inclusion cyst discovered almost 70 years after
      strabismus surgery.
AB  - Orbital conjunctival epithelial inclusion cysts are a rare complication of
      strabismus surgery. A subconjunctival cystic mass with translucent fluid is the
      most common presentation. The authors describe a case of an epithelial inclusion
      cyst presenting as an occult orbital mass during reoperation strabismus surgery
      almost 70 years after strabismus surgery.

PMID- 25384307
TI  - Inflammation and the blood microvascular system.
AB  - Acute and chronic inflammation is associated with changes in microvascular form
      and function. At rest, endothelial cells maintain a nonthrombogenic, nonreactive
      surface at the interface between blood and tissue. However, on activation by
      proinflammatory mediators, the endothelium becomes a major participant in the
      generation of the inflammatory response. These functions of endothelium are
      modified by the other cell populations of the microvessel wall, namely pericytes,
      and smooth muscle cells. This article reviews recent advances in understanding
      the roles played by microvessels in inflammation. 

PMID- 25384313
TI  - Effects on growth of human osteoblast-like cells of three nonsteroidal anti
      inflammatory drugs: metamizole, dexketoprofen, and ketorolac.
AB  - Some nonsteroidal anti-inflammatory drugs (NSAIDs) have adverse effects on bone
      tissue. The objective of this study was to determine the effect of different
      doses of dexketoprofen, ketorolac, and metamizole on growth of the osteoblast
      MG63 cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      spectrophotometry results showed that MG63 cell growth was significantly
      inhibited after 24 hr of culture with doses of 10, 20, 100, or 1,000 uM of each
      NSAID and with doses of 0.1, 1, or 5 uM of dexketoprofen and ketorolac but not
      metamizole. Cell-cycle studies revealed that dexketoprofen and ketorolac
      treatments significantly arrested the cell cycle in phase G0/G1, increasing the
      percentage of cells in this phase. Apoptosis/necrosis studies showed significant
      changes versus control cells, with an increased percentage of cells in apoptosis
      after treatment with 10, 100, or 1,000 uM of metamizole and after treatment with
      1, 10, 100, or 1,000 uM of dexketoprofen or ketorolac. In conclusion, treatment
      of osteoblast-like cells with high doses of the NSAIDs tested increased not only
      the percentage of cells in apoptosis but also the percentage of necrotic cells. 

PMID- 25384331
TI  - Authors' reply: High-resolution manometry in swallow syncope-is there a role?

PMID- 25384332
TI  - In response to "Conclusive strategies for therapy and virotyping of Helicobacter
      pylori".

PMID- 25384333
TI  - Different synthesis protocols for Co3O4 -CeO2 catalysts--part 1: influence on the
      morphology on the nanoscale.
AB  - Co3 O4 -modified CeO2 (Co/Ce 1:4) was prepared by a combination of sol-gel
      processing and solvothermal treatment. The distribution of Co was controlled by
      means of the synthesis protocol to yield three different morphologies, namely,
      Co3 O4 nanoparticles located on the surface of CeO2 particles, coexistent Co3 O4
      and CeO2 nanoparticles, or Co oxide structures homogeneously distributed within
      CeO2 . The effect of the different morphologies on the properties of Co3 O4 -CeO2
      was investigated with regard to the crystallite phase(s), particle size, surface
      area, and catalytic activity for CO oxidation. The material with Co3 O4
      nanoparticles finely dispersed on the surface of CeO2 particles had the highest
      catalytic activity. 

PMID- 25384334
TI  - Letter to the editor regarding "detection of the 35S promoter in transgenic maize
      via various isothermal amplification techniques: a practical approach".

PMID- 25384335
TI  - Quantitative profiling of bile acids in blood, adipose tissue, intestine, and
      gall bladder samples using ultra high performance liquid chromatography-tandem
      mass spectrometry.
AB  - An ultra high performance liquid chromatography tandem mass spectrometry method
      (UHPLC-MS/MS) was developed for the determination of 33 target and 28 unknown
      bile acids (BAs) in biological samples. Sixty-one BAs could be measured in 20 min
      using only a small amount of sample and with a simple sample preparation. The
      method proved to be very sensitive (limit of detection 5-350 pg/mL, lower limit
      of quantitation 0.1-2.6 ng/mL), linear (R(2) > 0.99) and reproducible (typically
      CV <15 % in biological matrixes). The method was used to analyze human adipose
      tissue, plasma, and serum (from same subjects) and mouse serum, gall bladder,
      small intestine, and colon samples (from same animals). Cholic acid,
      ursodeoxycholic acid, and chenodeoxycholic acid, deoxycholic acid, and their
      conjugates (mainly glycine, but also taurine conjugates) were the main
      metabolites in human samples, and cholic acid, glycine cholic acid, and several
      taurine conjugates in mouse samples. Using the method, 28 unknown BAs could also
      be detected. UHPLC-MS/MS spectra, accurate mass, and tissue distribution
      suggested that nine of the unknown bile acids were taurine conjugates, 13 were
      glycine conjugates, and six were intact BAs, respectively. To our knowledge, this
      was the first time BAs were detected in adipose tissue. Results showed that 17
      targeted BAs were found at ng/g level in human adipose tissue. Our findings give
      a novel insight of the endogenous role of BAs in adipose tissue and their role as
      biomarkers (e.g., in metabolic diseases). 

PMID- 25384336
TI  - Determination of sulfonamides in butter samples by ionic liquid magnetic bar
      liquid-phase microextraction high-performance liquid chromatography.
AB  - A novel, simple, and environmentally friendly pretreatment method, ionic liquid
      magnetic bar liquid-phase microextraction, was developed for the determination of
      sulfonamides in butter samples by high-performance liquid chromatography. The
      ionic liquid magnetic bar was prepared by inserting a stainless steel wire into
      the hollow of a hollow fiber and immobilizing ionic liquid in the micropores of
      the hollow fiber. In the extraction process, the ionic liquid magnetic bars were
      used to stir the mixture of sample and extraction solvent and enrich the
      sulfonamides in the mixture. After extraction, the analyte-adsorbed ionic liquid
      magnetic bars were readily isolated with a magnet from the extraction system. It
      is notable that the present method was environmentally friendly since water and
      only several microliters of ionic liquid were used in the whole extraction
      process. Several parameters affecting the extraction efficiency were investigated
      and optimized, including the type of ionic liquid, sample-to-extraction solvent
      ratio, the number of ionic liquid magnetic bars, extraction temperature,
      extraction time, salt concentration, stirring speed, pH of the extraction
      solvent, and desorption conditions. The recoveries were in the range of 73.25
      103.85 % and the relative standard deviations were lower than 6.84 %. The
      experiment results indicated that the present method was effective for the
      extraction of sulfonamides in high-fat content samples. 

PMID- 25384337
TI  - Global DNA hypomethylation in prostate cancer development and progression: a
      systematic review.
AB  - BACKGROUND: The role of global DNA methylation in prostate cancer (PCa) remains
      largely unknown. Our aim was to summarize evidence on the role of global DNA
      hypomethylation in PCa development and progression. METHODS: We searched PubMed
      through December 2013 for all studies containing information on global
      methylation levels in PCa tissue and at least one non-tumor comparison tissue
      and/or studies reporting association between global methylation levels in PCa
      tissue and survival, disease recurrence or at least one clinicopathological
      prognostic factor. We summarized results using non-parametric comparisons and P
      value summary methods. RESULTS: We included 15 studies in the review: 6 studies
      with both diagnostic and prognostic information, 5 studies with only diagnostic
      information and 4 studies with only prognostic information. Quantitative meta
      analysis was not possible because of the large heterogeneity in molecular
      techniques, types of tissues analyzed, aims and study designs. Summary
      statistical tests showed association of DNA hypomethylation with PCa diagnosis
      (P<0.006) and prognosis (P<0.001). Restriction to studies assessing 5
      methylcytosine or long interspersed nucleotide element-1 revealed results in the
      same direction. Analyses restricted to specific clinicopathological features
      showed association with the presence of metastasis and tumor stage in all tests
      with P<0.03, and no association with Gleason score (all tests P>0.1 except for
      the weighted Z-test, P=0.05). CONCLUSION: DNA hypomethylation was associated with
      PCa development and progression. However, due to the heterogeneity and small
      sample sizes of the included studies, along with the possibility of publication
      bias, this association requires additional assessment.

PMID- 25384339
TI  - Expression and localization of Nlrp4g in mouse preimplantation embryo.
AB  - The Nlrp gene family contains 20 members and plays a pivotal role in the innate
      immune and reproductive systems in the mouse. During evolution, seven Nlrp4 gene
      copies (named from Nlrp4a to Nlrp4g). Nlrp4a-Nlrp4g have arisen that display
      specific or preferential ovarian expression patterns. However, the expression
      pattern and localization of Nlrp4g in mouse preimplantation embryo development
      are unknown. Here we report that Nlrp4g was highly expressed in mature oocytes
      and zygotes, then downregulated and not detected after the 2-cell embryo stage.
      NLRP4G protein remained present through the blastocyst stage and was mainly
      localized in the cytoplasm. Furthermore, overexpression of Nlrp4g in zygotes did
      not affect normal development in terms of the rate of blastocyst formation. These
      results provide the first evidence that NLRP4G is a maternal factor that may play
      essential role during zygotic genome activation in the mouse. 

PMID- 25384338
TI  - Change in PSA velocity is a predictor of overall survival in men with
      biochemically-recurrent prostate cancer treated with nonhormonal agents: combined
      analysis of four phase-2 trials.
AB  - BACKGROUND: Multiple phase-2 trials in men with biochemically-recurrent prostate
      cancer (BRPC) have assessed the impact of nonhormonal agents on PSA kinetics. We
      have previously demonstrated that changes in PSA kinetics correlate with
      metastasis-free survival; however, it is unknown whether these changes also
      correlate with overall survival (OS). METHODS: We performed a combined
      retrospective analysis of 146 men with BRPC treated on phase-2 trials using one
      of four investigational drugs: lenalidomide (n=60), marimastat (n=39), ATN-224
      (n=22) and imatinib (n=25). We examined factors influencing OS, including within
      subject changes in PSA kinetics (PSA slope, PSA doubling time and PSA velocity),
      before and 6 months after treatment initiation. RESULTS: After a median follow-up
      of 83.1 months, 49 of 146 men had died. In univariate Cox regression analysis,
      two factors were associated with OS: baseline PSA velocity and change in PSA
      velocity on therapy. In a landmark multivariable model, stratified by study
      (which controlled for age, Gleason score, type of local therapy and use of
      androgen-deprivation therapy prior to metastases), baseline PSA velocity and
      increase in PSA velocity on therapy remained independent predictors of OS. Median
      OS for men with an increase in PSA velocity on treatment was 115.4 months and was
      not reached for men with a decrease in PSA velocity (hazard ratio=0.47, 95%
      confidence interval 0.25-0.88; P=0.02). CONCLUSIONS: This hypothesis-generating
      study suggests that within-subject changes in PSA velocity after initiation of
      nonhormonal therapy may correlate with OS in men with BRPC. If validated in
      prospective trials, change in PSA velocity may represent a reasonable
      intermediate end point for screening new agents in these patients.

PMID- 25384340
TI  - Isolation, characterization and application of a cellulose-degrading strain
      Neurospora crassa S1 from oil palm empty fruit bunch.
AB  - BACKGROUND: Oil palm empty fruit bunch (EFB) is a lignocellulosic waste produced
      in palm oil industry. EFB mainly consists of cellulose, hemicellulose (mainly
      xylan) and lignin and has a great potential to be reused. Converting EFB to
      fermentable sugars and value-added chemicals is a much better choice than
      treating EFB as waste. RESULTS: A cellulase-producing strain growing on oil palm
      empty fruit bunch (EFB) was isolated and identified as Neurospora crassa S1,
      which is able to produce cellulases using EFB as the sole carbon source. The
      strain started to secret cellulases into the medium after 24 h of cultivation at
      30 degrees C and reached its maximal cellulase activity at 240 h. Mass
      spectroscopy (MS) analysis showed that more than 50 proteins were secreted into
      the medium when EFB was used as the sole carbon source. Among them, 7 proteins
      were identified as putative enzymes associated with cellulose degradation. The
      whole cell culture of Neurospora crassa S1 was used to hydrolyze acid-treated
      EFB, giving a total sugar yield of 83.2%, which is comparable with that (82.0%)
      using a well-known cellulase producer Trichoderma reesei RUT-C30 (ATCC56765).
      CONCLUSION: Neurospora crassa S1 is a commercially promising native cellulase
      producer for EFB hydrolysis especially when the sugars obtained are to be
      fermented to products that require use of non-genetically engineered strains.

PMID- 25384341
TI  - Temporal trend might be better than instant occurrence of fQRS as a noninvasive
      prognostic marker in STEMI patients undergoing primary PCI.

PMID- 25384342
TI  - Phytoferritin association induced by EGCG inhibits protein degradation by
      proteases.
AB  - Phytoferritin is a promising resource of non-heme iron supplementation, but it is
      not stable against degradation by proteases in the gastrointestinal tract.
      Therefore, how to improve the stability of ferritin in the presence of proteases
      is a challenge. Since (-)-epigallocatechin-3-gallate (EGCG) is rich in phenolic
      hydroxyl groups, it could interact with ferritin through hydrogen bonds, thereby
      preventing protein from degradation. To confirm this idea, we focus on the
      interaction between EGCG and phytoferritin, and the consequence of such
      interaction. Results demonstrated that EGCG did interact with ferritin, and such
      interaction induced the change in the tertiary/quaternary structure of protein
      but not in its secondary structure. Furthermore, stopped-flow and dynamic light
      scattering (DLS) results showed that EGCG could trigger ferritin association.
      Consequently, such protein association markedly inhibited protein digestion by
      pepsin at pH 4.0 and by trypsin at pH 7.5. These findings raise the possibility
      to improve the stability of phytoferritin in the presence of proteases.

PMID- 25384344
TI  - Degenerate nucleophilic substitution in phosphonium salts.
AB  - Rates and energy barriers of degenerate halide substitution on tetracoordinate
      halophosphonium cations have been measured by NMR techniques (VT and EXSY) using
      a novel experimental design whereby a chiral substituent ((s)Bu) lifts the
      degeneracy of the resultant salts. Concomitantly, a viable computational approach
      to the system was developed to gain mechanistic insights into the structure and
      relative stabilities of the species involved. Both approaches strongly suggest a
      two-step mechanism of formation of a pentacoordinate dihalophosphorane via
      backside attack followed by dissociation, resulting in inversion of configuration
      at phosphorus. The experimentally determined barriers range from <9 kcal mol(-1)
      to nearly 20 kcal mol(-1), ruling out a mechansm via Berry pseudorotation
      involving equatorial halides. In all cases studied, epimerization of
      chlorophosphonium chlorides has a lower energy barrier (by 2 kcal mol(-1)) than
      the analogous bromo salts. Calculations determined that this was due to the
      easier accessibility in solution of pentacoordinate dichlorophosphoranes when
      compared to analogous dibromophosphoranes. In line with the proposed associative
      mechanism, bulky substituents slow the reaction in the order Me < Et < (i)Pr <
      (t)Bu. Bulky substituents affect the shape of the reaction energy profile so that
      the pentacoordinate intermediate is destabilized eventually becoming a transition
      state. The magnitude of the steric effects is comparable to that of the same
      substituents on substitution at primary alkyl halides, which can be rationalized
      by the relatively longer P-C bonds. The reaction displays first-order kinetics
      due to the prevalence of tight- or solvent-separated ion pairs in solution. Three
      dimensional reaction potential energy profiles (More O'Ferrall-Jencks plots)
      indicated a relatively shallow potential well corresponding to the trigonal
      bipyramid intermediate flanked by two transition states. 

PMID- 25384345
TI  - Solution-processed VO2-SiO2 composite films with simultaneously enhanced luminous
      transmittance, solar modulation ability and anti-oxidation property.
AB  - Recently, researchers spare no efforts to fabricate desirable vanadium dioxide
      (VO2) film which provides simultaneously high luminous transmittance and
      outstanding solar modulation ability, yet progress towards the optimization of
      one aspect always comes at the expense of the other. Our research devotes to
      finding a reproducible economic solution-processed strategy for fabricating VO2
      SiO2 composite films, with the aim of boosting the performance of both aspects.
      Compare to VO2 film, an improvement of 18.9% (from 29.6% to 48.5%) in the
      luminous transmittance as well as an increase of 6.0% (from 9.7% to 15.7%) in
      solar modulation efficiency is achieved when the molar ratio of Si/V attains 0.8.
      Based on the effective medium theory, we simulate the optical spectra of the
      composite films and the best thermochromic property is obtained when the filling
      factor attains 0.5, which is consistent with the experimental results. Meanwhile,
      the improvement of chemical stability for the composite film against oxidation
      has been confirmed. Tungsten is introduced to reduce the phase transition
      temperature to the ambient temperature, while maintain the thermochromism
      required for application as smart window. Our research set forth a new avenue in
      promoting practical applications of VO2-based thermochromic fenestration. 

PMID- 25384343
TI  - Characteristics of CARMA1-BCL10-MALT1-A20-NF-kappaB expression in T cell-acute
      lymphocytic leukemia.
AB  - BACKGROUND: Knowledge of the oncogenic signaling pathways of T-cell acute
      lymphoblastic leukemia (T-ALL) remains limited. Constitutive aberrant activation
      of the nuclear factor kappa B (NF-kappaB) signaling pathway has been detected in
      various lymphoid malignancies and plays a key role in the development of these
      carcinomas. The zinc finger-containing protein, A20, is a central regulator of
      multiple NF-kappaB-activating signaling cascades. A20 is frequently inactivated
      by deletions and/or mutations in several B-and T-cell lymphoma subtypes. However,
      few A20 mutations and polymorphisms have been reported in T-ALL. Thus, it is of
      interest to analyze the expression characteristics of A20 and its regulating
      factors, including upstream regulators and the CBM complex, which includes
      CARMA1, BCL10, and MALT1. METHODS: The expression levels of CARMA1, BCL10, MALT1,
      A20, and NF-kappaB were detected in peripheral blood mononuclear cells (PBMCs)
      from 21 patients with newly diagnosed T-ALL using real-time PCR, and correlations
      between the aberrant expression of these genes in T-ALL was analyzed. Sixteen
      healthy individuals, including 10 males and 6 females, served as controls.
      RESULTS: Significantly lower A20 expression was found in T-ALL patients (median:
      4.853) compared with healthy individuals (median: 8.748; P = 0.017), and
      significantly increased expression levels of CARMA1 (median: 2.916; P = 0.034),
      BCL10 (median: 0.285; P = 0.033), and MALT1 (median: 1.201; P = 0.010) were found
      in T-ALL compared with the healthy individuals (median: 1.379, 0.169, and 0.677,
      respectively). In contrast, overexpression of NF-kappaB (median: 0.714) was found
      in T-ALL compared with healthy individuals (median: 0.335; P = 0.001). A negative
      correlation between the MALT1 and A20 expression levels and a positive
      correlation between CARMA1 and BCL10 were found in T-ALL and healthy individuals.
      However, no negative correlation was found between A20 and NF-kappaB and the
      MALT1 and NF-kappaB expression level in the T-ALL group. CONCLUSIONS: We
      characterized the expression of the CARMA-BCL10-MALT1-A20-NF-kappaB pathway genes
      in T-ALL. Overexpression of CARMA-BCL10-MALT in T-ALL may contribute to the
      constitutive cleavage and inactivation of A20, which enhances NF-kappaB signaling
      and may be related to T-ALL pathogenesis.

PMID- 25384346
TI  - Antitumor activity of adenoviral vector containing T42 and 4xT42 peptide gene
      through inducing apoptosis of tumor cells and suppressing angiogenesis.
AB  - The T42 peptide, generated from two active fragments of tumstatin, has been shown
      to have anti-tumor activity. The adenoviral vector is the most frequently used
      vector in research and clinical trials for gene therapy. In the present study,
      the anti-tumor activity of the T42 peptide and quadruple T42 (4xT42) peptide
      adenoviral vectors were elucidated for the first time, to the best of our
      knowledge. Human embryonic kidney 293 cells were infected with plasmid adenovirus
      (pAd)-enhanced green fluorescent protein (EGFP)-T42 or pAd-EGFP-4xT42 and the
      expression of the T42 and 4xT42 genes was confirmed by the identification of GFP
      expression and reverse transcription polymerase chain reaction experiments. The
      anti-cancer effects of pAd-EGFP-T42 and pAd-EGFP-4xT42 on breast cancer cells in
      vivo and in vitro were subsequently investigated. The results indicated that the
      packaging of the recombinant adenoviruses with the viral titer was successful,
      following purification at 5x109 plaque forming units/ml. The results also
      revealed that the recombinant adenoviruses promoted apoptosis in MCF-7 breast
      cancer cells and inhibited cancer growth. Through the analysis of caspase-3, B
      cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein expression, it was
      demonstrated that the T42/4xT42 peptide may induce apoptosis via the
      mitochondrial pathway. In addition, mouse xenograft experiments confirmed that
      the T42 peptide inhibited tumor growth and reduced angiogenesis in vivo. In
      conclusion, the results of the present study indicated that the T42 and 4xT42
      peptide genes, transfected by a recombinant adenovirus, may provide a potential
      novel strategy for the treatment of breast cancer.

PMID- 25384348
TI  - Autonomous-related self, eating attitude and body satisfaction in young females.
AB  - PURPOSE: This research aimed to investigate the relationship between the self,
      eating attitudes, and body satisfaction within the framework of the autonomous
      related self model, in which the healthy functioning self is described as
      "autonomous" and "related." METHODS: Female university students (n = 314) with a
      mean age of 19 (SD = 1.18) were included in the research. The mean body mass
      index (BMI) of participants was 20.77 (SD = 2.77, range = 15.57-33.06).
      Participants completed a demographics questionnaire, the Autonomy-Relatedness
      Scales, Eating Attitudes Test, Body Cathexis Scale, and Beck Depression
      Inventory. RESULTS: Lower autonomy-relatedness (beta = -0.13, p < 0.05) predicted
      more problematic eating attitudes, but autonomy-relatedness itself was not a
      significant predictor of body satisfaction in young females. Ideal weight scores
      (beta = -0.19, p < 0.01) negatively predicted a disturbance in eating attitudes,
      whereas depression scores (beta = 0.12, p < 0.05) positively predicted a
      disturbance. Although none of the self-constructs (autonomy, relatedness,
      autonomy-relatedness) were significant predictors of body satisfaction, BMI (beta
      = -0.20, p < 0.001), and depressive symptoms (beta = -0.28, p < 0.001) negatively
      predicted body satisfaction, whereas ideal weight scores (beta = 0.14, p < 0.01)
      positively predicted body satisfaction. CONCLUSIONS: The Autonomous-Related Self
      was a meaningful measure of associations between the self and eating
      psychopathology, but not of the relationship between the self and body
      satisfaction. It was also important to evaluate objective (e.g., BMI) and
      subjective (e.g., ideal weight) indicators of weight to better understand the
      nature of eating patterns and body satisfaction. Future research on autonomy
      relatedness and other psychopathology is recommended.

PMID- 25384349
TI  - Can ambulatory blood pressure monitoring detect early diastolic dysfunction in
      children with type 1 diabetes mellitus: correlations with B-type natriuretic
      peptide and tissue Doppler findings.
AB  - AIM: To evaluate the relationship between 24-h blood pressure (BP) measurements
      and diastolic heart function evaluated by Doppler tissue imaging and B-type
      natriuretic peptide (BNP) levels in children with type 1 diabetes mellitus (DM).
      PATIENTS AND METHODS: A total of 32 diabetic and 18 healthy children were
      enrolled. Spectral Doppler analysis and tissue Doppler measurements were
      performed by conventional echocardiography. The 24-h ambulatory BP and serum BNP
      levels were measured. RESULTS: Analysis of ambulatory blood pressure monitoring
      (ABPM) recordings showed that median daytime diastolic BP load were significantly
      higher in diabetic patients compared to controls [12.35 (4.23-27.23) vs. 2.5 (0
      8.7), p = 0.007]. Patients with elevated daytime systolic and diastolic BP loads
      had significantly higher BNP values compared to patients with normal BP load
      (31.4 +/- 24.36 vs. 11.84 +/- 11.25 pg/mL, p = 0.03 and 23.21 +/- 15.12 vs. 12.12
      +/- 14.65 pg/mL, p = 0.03, respectively). Isovolemic contraction time (47.43 +/-
      7.84 vs. 42.27 +/- 7.47, p = 0.045), isovolemic relaxation time (68.84 +/- 10.43
      vs. 58.77 +/- 10.02, p = 0.02), and myocardial performance index (0.45 +/- 0.10
      vs. 0.37 +/- 0.09, p = 0.02) as determined by tissue Doppler echocardiography
      were significantly high in diabetic patients compared to that of control cases.
      Ratio of mitral peak early diastolic flow velocity (E) to peak early diastolic
      myocardial velocities by tissue Doppler echocardiography (E') was also higher in
      patients with elevated daytime systolic BP load (E/E', 6.71 +/- 1.97 vs. 4.91 +/-
      1.02, p = 0.04). CONCLUSION: Elevated BP loads detected by 24-h ambulatory BP
      measurements in children with type 1 diabetes are associated with increased BNP
      levels and abnormal tissue Doppler echocardiography indices, indicating early
      stage cardiac dysfunction.

PMID- 25384350
TI  - Photodegradation of C-PCPDTBT and Si-PCPDTBT: influence of the bridging atom on
      the stability of a low-band-gap polymer for solar cell application.
AB  - The kinetics of photodegradation and the reactivity of different sites of the low
      band-gap polymers poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4
      b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (C-PCPDTBT) and poly[2,6-(4,4
      bis-(2-ethylhexyl)dithieno[3,2-b:2',3'-d]silole)-alt-4,7-(2,1,3
      benzothiadiazole)] (Si-PCPDTBT) are investigated as thin films and are compared
      to those of poly(3-hexylthiophene) (P3HT). The decay kinetics are monitored with
      UV/Vis spectroscopy and the reactivity and product evolution are investigated
      with X-ray photoelectron spectroscopy (XPS). Both polymers exhibit higher
      stability than P3HT. The bridging atom in the cyclopentadithiophene (CPDT)
      subunit has a significant influence on the stability. Varying oxidation rates for
      the different elements were observed. In the case of Si-PCPDTBT, the silicon atom
      is oxidized primarily, whereas the photooxidation rates of the other elements are
      reduced relative to C-PCPDTBT. Additionally, XPS experiments with varying
      excitation energies reveal a significant reaction gradient within a few
      nanometers of the surface of degraded thin films of C-PCPDTBT. 

PMID- 25384351
TI  - Atypical femoral fracture in osteoporosis pseudoglioma syndrome associated with
      two novel compound heterozygous mutations in LRP5.
AB  - Osteoporosis pseudoglioma syndrome (OPPG) is a rare autosomal recessive condition
      of congenital blindness and severe childhood osteoporosis with skeletal
      fragility, caused by loss-of-function mutations in the low-density lipoprotein
      receptor-related protein 5 (LRP5) gene. We report the first case of atypical
      (subtrochanteric) femoral fracture (AFF) in OPPG, occurring in a 38-year-old man
      within the context of relatively low bone turnover and trabecular osteoporosis on
      bone histology. We identify two novel LRP5 mutations: R752W is associated with
      low bone mineral density (BMD), as demonstrated by the heterozygous carriage
      identified in his 57-year-old mother; however, the combination of this R752W
      mutation with another novel W79R mutation, causes a severe case of compound
      heterozygous OPPG. We undertake 3D homology modeling of the four extracellular
      YWTD beta-propeller/EGF-like domains (E1-E4) of LRP5, and show that both novel
      mutations destabilize the beta-propeller domains that are critical for protein
      and ligand binding to regulate Wnt signaling and osteoblast function. Although
      AFFs have been reported in other rare bone diseases, this is the first in a
      genetic condition of primary osteoblast dysfunction. The relatively low bone
      turnover observed, and knowledge of LRP5 function, implicates impaired bone
      remodeling in the pathogenesis of AFF.

PMID- 25384352
TI  - Utility of magneto-electropolished ternary nitinol alloys for blood contacting
      applications.
AB  - The thrombogenicity of a biomaterial is mainly dependent on its surface
      characteristics, which dictates its interactions with blood. Surface properties
      such as composition, roughness wettability, surface free energy, and morphology
      will affect an implant material's hemocompatibility. Additionally, in the realm
      of metallic biomaterials, the specific composition of the alloy and its surface
      treatment are important factors that will affect the surface properties. The
      utility of magneto-electropolished (MEP) ternary Nitinol alloys, NiTiTa, and
      NiTiCr as blood contacting materials was investigated. The hemcompatibility of
      these alloys were compared to mechanically polished (MP) metallic biomaterial
      counterparts. In vitro thrombogenicity tests revealed significantly less platelet
      adherence on ternary MEP Nitinol, especially MEP NiTi10Ta as compared to the MP
      metals (p < 0.05). The enhanced anti-platelet-adhesive property of MEP NiTi10Ta
      was in part, attributed to the Ta2 O5 component of the alloy. Furthermore, the
      formation of a dense and mixed hydrophobic oxide layer during MEP is believed to
      have inhibited the adhesion of negatively charged platelets. In conclusion, MEP
      ternary Nitinol alloys can potentially be utilized for blood-contacting devices
      where, complications resulting from thrombogenicity can be minimized.

PMID- 25384353
TI  - Management of diarrhea in HIV-affected infants and children.
AB  - Globally, diarrhea is the second leading cause of death in children less than 5
      years of age. HIV-infected and HIV-exposed uninfected (HEU) children are at high
      risk of dying from diarrhea and may be more susceptible to the highest risk
      enteric pathogens. This increased risk associated with HIV infection and HIV
      exposure is likely multifactorial. Factors such as immunosuppression, proximity
      to individuals more likely to be shedding pathogens, and exposure to
      antimicrobial prophylaxis may alter the risk profile in these children. Current
      international guidelines do not differentiate management strategies on the basis
      of whether children are infected or affected by HIV, despite likely differences
      in etiologies and consequences. Reducing diarrhea mortality in high HIV
      prevalence settings will require strengthening of HIV testing and treatment
      programs; improvements in water, sanitation and hygiene interventions targeted at
      HIV-affected households; and reconsideration of the use of empiric antimicrobial
      treatment of pathogens known to infect HIV-infected and HEU children
      disproportionately. 

PMID- 25384354
TI  - Eruption of a deep-sea mud volcano triggers rapid sediment movement.
AB  - Submarine mud volcanoes are important sources of methane to the water column.
      However, the temporal variability of their mud and methane emissions is unknown.
      Methane emissions were previously proposed to result from a dynamic equilibrium
      between upward migration and consumption at the seabed by methane-consuming
      microbes. Here we show non-steady-state situations of vigorous mud movement that
      are revealed through variations in fluid flow, seabed temperature and seafloor
      bathymetry. Time series data for pressure, temperature, pH and seafloor
      photography were collected over 431 days using a benthic observatory at the
      active Hakon Mosby Mud Volcano. We documented 25 pulses of hot subsurface fluids,
      accompanied by eruptions that changed the landscape of the mud volcano. Four
      major events triggered rapid sediment uplift of more than a metre in height,
      substantial lateral flow of muds at average velocities of 0.4 m per day, and
      significant emissions of methane and CO2 from the seafloor.

PMID- 25384355
TI  - Monitoring changes of tumor microenvironment in colorectal submucosa using
      multiphoton microscopy.
AB  - Recently, targeting tumor microenvironment has become a novel approach for cancer
      therapy. Collagen is one of important components of tissue microenvironment, and
      has been considered as a new visible target for cancer therapy. In this work,
      multiphoton microscopy (MPM) was used to monitor the changes of collagen in tumor
      microenvironment during tumor progression. It was found that MPM facilitates
      imaging of tumor cells and collagen. MPM images in different tumor
      microenvironment during tumor progression shows obvious increase in cell number
      and collagen degration. In addition, the quantitative analysis of collagen
      content and orientation index in tumor microenvironment shows significant
      alteration during tumor progression. These results suggest that MPM has the
      ability to monitor the changes of collagen morphology in tumor microenvironment
      and quantify content and orientation index of collagen during tumor progression.
      Therefore this technique is a powerful imaging tool for the investigation of
      targeting tumor microenvironment for cancer therapy.

PMID- 25384356
TI  - Successful single-sided renal denervation in drug-resistant hypertension and
      ventricular tachycardia.

PMID- 25384358
TI  - Carbon coated MnO@Mn3N2 core-shell composites for high performance lithium ion
      battery anodes.
AB  - Carbon coated MnO@Mn(3)N(2) core-shell composites (MnO@Mn(3)N(2)/C) were
      synthesized in a simple approach by calcining MnO(2) nanowires with urea at 800 
      degrees C under an ammonia atmosphere. Urea derived carbon nanosheets were
      partially coated on pure phase MnO@Mn(3)N(2) core-shell composites.
      Electrochemical measurements reveal that the MnO@Mn(3)N(2)/C displayed high
      discharge capacities, an excellent high-rate capability and an enhanced cycling
      performance.

PMID- 25384357
TI  - Treatment as prevention--where next?
AB  - Uptake of antiretroviral regimens with associated durable virologic suppression
      has been shown to reduce the risk of HIV transmission. Expanding antiretroviral
      therapy (ART) programs at a population level may serve as a vital strategy in the
      elimination of the AIDS epidemic. The global expansion of ART programs has
      greatly improved access to life-saving therapies and is likely to achieve the
      target of 15 million individuals on therapy set by UNAIDS. In addition to the
      incontrovertible gains in terms of life expectancy, growing evidence demonstrates
      that durable virologic suppression is associated with significant reductions in
      HIV transmission amongst heterosexual couples and men who have sex with men.
      Expansion of successful ART programs, best monitored by a program-level continuum
      of care cascade to assess progress in diagnosis, retention in care, and virologic
      suppression, is associated with reductions in HIV incidence at a population
      level. Expanding and sustaining successful ART delivery at a global level is a
      key component in a comprehensive approach to combating the HIV epidemic over the
      next two decades. 

PMID- 25384359
TI  - Outcome and prognostic factors of local recurrent rectal cancer: a pooled
      analysis of 150 patients.
AB  - BACKGROUND: Surgery is the only curative treatment in patients with locally
      recurrent rectal cancer (LRRC). The aim of this study was to evaluate the outcome
      and the prognostic factors of tumour-free resection margin (R0) and overall
      survival (OS) in LRRC. METHODS: Consecutive LRRC patients observed between 1987
      and 2005 in three Italian university hospitals were evaluated. Survival curves
      were estimated using the Kaplan-Meier method and compared with the log-rank test.
      In order to identify factors associated with both R0 resection and OS, a logistic
      regression analysis was performed in patients who underwent surgery with curative
      intent. RESULTS: Out of 150 patients with LRRC, 107 underwent surgery, but since
      7 were found to have unresectable disease only 100 underwent surgical resection.
      Of them, 51 underwent radical and 49 extended resection. Sixty of the 107
      patients underwent multimodality treatment. In 61 patients, R0 resection was
      achieved. Median OS after surgery was 43.4 months. In patients, who had surgery
      with curative intent, independent variables associated with R0 resection were:
      surgery for the primary tumour performed in other hospitals (p = 0.042) extended
      resection (p = 0.025) and use of positron emission tomography (PET) as a staging
      modality (p = 0.03). Independent variables associated with OS were: post
      operative radiotherapy (p = 0.004), stage of the primary tumour (p = 0.004), R0
      resection (p = 0.00001), and use of PET (0.02). CONCLUSIONS: Resection for LRRC
      results in improved survival. Other than the well-known prognostic factors R0
      resection and OS, PET scan has an independent impact both on OS and R0 resection.
      It should therefore be included in routine clinical practice when staging LRRC.

PMID- 25384360
TI  - Extralevator versus standard abdominoperineal excision for rectal cancer.
AB  - BACKGROUND: Extralevator abdominoperineal excision (ELAPE) probably improves the
      oncological quality of low rectal cancer surgery, as compared to standard
      abdominoperineal excision (SAPE), possibly due to lower rates of accidental
      perioperative bowel perforations and lower rates of circumferential resection
      margin (CRM) positivity. The procedure may however, increase post-operative
      morbidity. The aim of this paper was to compare outcomes of SAPE and ELAPE for
      carcinoma of the lower rectum. METHODS: This is a retrospective study of patients
      operated on at a single colorectal unit, in a provincial hospital in Denmark.
      Consecutive patients undergoing abdominoperineal excision (APE) between 2006 and
      2012 were included. During this period, a gradual paradigm shift occurred towards
      adopting ELAPE, although both procedures were performed without a clear selection
      strategy. We reviewed medical records, including the pathological and
      radiological data. Patients were divided into two groups, SAPE and ELAPE. Main
      endpoints were rates of positive CRM, intraoperative bowel perforations, local
      recurrence rate, length of hospital stay, operative time, and perineal wound
      related complications. RESULTS: One hundred and seven patients were included
      (median age 68 years, range 42-88 years; men = 72). The SAPE group included 39
      patients and the ELAPE group 68 patients. Intraoperative bowel perforation was
      significantly lower in the ELAPE group (20.5% SAPE vs 7.4% ELAPE, p = 0.045). The
      rate of positive CRM was not significantly different (2.6% SAPE vs 7.4% ELAPE, p
      = 0.413). The local recurrence rate was not statistically significant (17.9% SAPE
      vs 13.2% ELAPE, p = 0.513). In the ELAPE group, operative time and hospital stay
      were significantly longer than the SAPE group (p = 0.001 and p = 0.021,
      respectively). CONCLUSIONS: We found low rates of positive CRM after APE compared
      with the literature. ELAPE did not reduce these rates, and although the local
      recurrence rate was lower, this did not reach statistical significance. ELAPE has
      significantly reduced the rate of intraoperative bowel perforation and can
      optimize low rectal cancer surgery in selected patients. We found no significant
      differences between the two procedures regarding wound-related complications. A
      tailored approach and a larger trial with longer follow-up are needed to evaluate
      long-term results.

PMID- 25384361
TI  - Long-term oncologic results of laparoscopic D3 lymphadenectomy with complete
      mesocolic excision for right-sided colon cancer with clinically positive lymph
      nodes.
AB  - BACKGROUND/AIM: To assess surgical outcomes of patients undergoing D3 lymph node
      dissection and complete mesocolic excision for the treatment of right-sided colon
      cancer in the context that both procedures were performed laparoscopically.
      METHODS: 244 consecutive patients with clinically staged III right-sided colon
      cancer were recruited to undergo the laparoscopic D3 lymph node dissection with
      complete mesocolic excision. Postoperatively, the patients were stratified as N0,
      N1, N2, and N3 groups according to the level of lymph node metastasis,
      prospectively followed up for more than 5 years, and compared. RESULTS: The 5
      year cumulative recurrence rate and the estimated time-to-recurrence [mean (95 %
      confidence interval)] was 16.6 % (n = 7/42), 113.8 (101.4-126.2) months in N0
      group; 21.3 % (n = 17/80), 108.9 (99.1-118.7) months in N1 group; 43.2 % (n =
      32/74), 85.4 (73.0-97.8) months in N2 group; and 52.0 % (n = 25/48), 65.2 (49.0
      81.4) months in N3 group. When N1 and N0 groups of patients were lumped together,
      and compared with patients with N2 or N3 metastasis, we found that the latter
      were with a significantly higher recurrence rate (p < 0.0001). D3 lymph node
      dissection with complete mesocolic excision could assure the harvest of
      sufficient number (n = 34.4 +/- 8.4) of lymph nodes for precise pathologic cancer
      staging. Skip lymph node metastasis was detected in 19.8 % (n = 40/202) of
      patients, and such surgical procedures facilitated up-staging in 4.5 % (n =
      11/244) of patients. CONCLUSION: The present study encourages the dissemination
      of such concepts to surgical oncologists dealing with colorectal cancer through
      didactic education, and international consensus meeting is therefore mandatory to
      optimize the surgery of colon cancer.

PMID- 25384362
TI  - The hysterical organization.
AB  - The term hysteria has been used in the history of the psychoanalytical movement
      to describe a large variety of psychic modalities. What is the common denominator
      of the hysterias? The author suggests that ambivalence in relation to penetration
      in its passive form (vaginal desire), in its pregenital and genital valences,
      constitutes the essence of hysteria. It seems that the issue of hysteria thus
      configured finds its best resolution in the fantasy of an incorporeal
      penetration, which leads to orgasm, and spares one from the anxiety of
      destruction to the internal space as well as from the anxiety of guilt following
      the hoped for climax. The author is attempting to discern, by means of two case
      studies, how disembodied penetration, depending on whether it is fantasized or
      delusional, constitutes a solution, neurotic or psychotic respectively, to the
      issue of hysteria: the private theatre in neurosis, as well as the inhabited and
      influenced mind in psychosis (delusion of control), act as psychic figurations of
      vagina. 

PMID- 25384363
TI  - Low-dose gamma-irradiation induces dual radio-adaptive responses depending on the
      post-irradiation time by altering microRNA expression profiles in normal human
      dermal fibroblasts.
AB  - Exposure to high-dose ionizing radiation, including gamma-radiation, induces
      severe skin disorders. However, the biological consequences and molecular
      mechanisms responsible for the response of human skin to low-dose gamma-radiation
      (LDR) are largely unknown. In the present study, we demonstrate that LDR (0.1 Gy)
      induces distinct cellular responses in normal human dermal fibroblasts (NHDFs)
      depending on the post-irradiation time point. A MTT-based cell viability assay
      and propidium iodide staining-based cell cycle assay revealed that the viability
      and proportion of the cells in the G2/M phase were differed at 6 and 24 h post
      irradiation. Reverse transcription quantitative PCR (RT-qPCR) revealed that LDR
      significantly upregulated the mRNA expression of collagen type I alpha 1
      (COL1A1), but downregulated the mRNA expression of matrix metalloproteinase 1
      (MMP1) at 24 h post-irradiation. MicroRNA (miRNA) microarray analysis further
      demonstrated that LDR induced changes in the expression profiles of specific
      miRNAs and that some of the deregulated miRNAs were specific to either the early
      or late radio-adaptive response. Our results suggest that LDR generates dual
      radio-adaptive responses depending on the post-irradiation time by altering
      specific miRNA expression profiles in NHDFs.

PMID- 25384364
TI  - Development of formulae for estimating amylose content, amylopectin chain length
      distribution, and resistant starch content based on the iodine absorption curve
      of rice starch.
AB  - Not only amylose but also amylopectin greatly affects the gelatinization
      properties of rice starch and the quality of cooked rice grains. We here
      characterized the starches of 32 rice cultivars and evaluated the relationship
      between their iodine absorption curve, apparent amylose content (AAC), pasting
      property, resistant starch (RS) content, and chain length distribution of
      amylopectin. We found that the iodine absorption curve differed among the various
      sample rice cultivars. Using the wavelength at which absorbance becomes maximum
      on iodine staining of starch (lambdamax), we propose a novel index, "new
      lambdamax" (AAC/(lambdamax of sample rice starches-lambdamax of glutinous rice
      starch)). We developed the novel estimation formulae for AAC, RS contents, and
      amylopectin fractions with the use of lambdamax and "new lambdamax." These
      formulae would lead to the improved method for estimating starch properties using
      an easy and rapid iodine colorimetric method. 

PMID- 25384365
TI  - Increased monocytic CD14+HLADRlow/- myeloid-derived suppressor cells in obesity.
AB  - Obesity is associated with numerous immunological disorders. The present study
      investigated the proportion and phenotype of myeloid-derived suppressor cells
      (MDSCs) in the plasma of obese subjects and the association of these cells with
      the level of liver enzymes. Certain features of the immune response in obese
      subjects were examined by analyzing the expression of T cell receptor-zeta
      (TCRzeta) molecules on the surface of T cells. The expression and secretion of
      S100A9, a possible marker for MDSCs, were detected in the peripheral blood of
      obese subjects and compared with levels in lean controls. Results showed that the
      percentage of monocytic MDSCs, with the phenotype CD33+CD11b+CD14+HLADRlow/-, was
      significantly increased in obese subjects compared with lean controls. The
      circulating level of monocytic MDSCs was positively correlated with the levels of
      liver enzymes in serum. The expression of the TCRzeta molecule in the resting T
      cells was significantly lower in obese individuals than that of lean controls.
      The expression of S100A9 was detected in the majority of monocytes in peripheral
      blood mononulear cells, but no difference was identified in the frequency of
      CD14+S100A9+ cells between the obese and lean groups. However, the plasma level
      of S100A8/9 was significantly increased in obese compared with lean subjects.
      These observations suggested that the increased frequency of
      CD33+CD11b+CD14+HLADRlow/- cells may be responsible for the impaired T-cell
      function and liver injury observed in obesity.

PMID- 25384366
TI  - Systemic panniculitis-like T-cell lymphoma with involvement of mesenteric fat and
      subcutis.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon non
      Hodgkins primary cutaneous lymphoma that typically presents as subcutaneous
      nodules on the extremities or trunk. Here, we report an unusual case of systemic
      panniculitic T-cell lymphoma with predominantly mesenteric extra-cutaneous
      involvement and an aggressive clinical course with histopathologic and
      immunophenotypic features that mimic SPTCL. This case serves to expand the body
      of literature regarding systemic SPTCL-like disorders with prominent extra
      cutaneous involvement. 

PMID- 25384367
TI  - Dementia in the incarcerated elderly adult: innovative solutions to promote
      quality care.
AB  - PURPOSE: To provide an overview of the epidemiology, pathophysiology, and
      diagnostic considerations of Alzheimer's disease (AD) with a special focus on
      elderly prison inmates. Multiple therapeutic interventions currently used for
      inmates with AD and a brief protocol for clinicians working with this population
      are provided. DATA SOURCES: Review of scientific literature. CONCLUSIONS: Early
      detection and appropriate treatment of AD and other dementias are particularly
      challenging inside of correctional institutions, and a lack of prison-specific
      guidelines for AD leaves clinicians struggling to deliver innovative, quality
      care to a vulnerable population of elderly inmates. IMPLICATIONS FOR PRACTICE:
      Clinicians working in prisons can promote optimal safety and health for each
      inmate through early diagnosis and treatment of those with dementia. Researchers
      studying dementia need to include the large incarcerated population in the United
      States in ongoing research and guideline development.

PMID- 25384368
TI  - Residue behavior of combination formulations of insecticides in/on cabbage and
      their efficacy against aphids and diamondback moth.
AB  - Persistence behavior of insecticides chlorpyriphos, profenofos, triazophos,
      cypermethrin, and deltamethrin following the use of three combination
      formulations Action 505 (chlorpyriphos + cypermethrin), Roket 44EC (profenofos +
      cypermethrin), and Anaconda Plus (triazophos + deltamethrin) was studied in
      cabbage following the spray application at the recommended and double doses. Bio
      efficacy of these formulations was also evaluated against mustard aphids
      (Lipaphis erysimi Kaltenbach) and diamondback moth (Plutella xylostella L.). The
      residues of different insecticides persisted for 5-8 days at low dose and 8-12
      days at high dose. The residues dissipated with time and 87-100% dissipation was
      recorded on the 8th day. The half-life values varied from 0.4 to 1.6 days. Based
      on the acceptable daily intake (ADI) values, a safe waiting period of 1 day has
      been suggested for the formulations Action 505 and Roket 44EC and 3 days for
      Anaconda Plus at the recommended dose of application. Action (1.6 L/ha) treatment
      was found to be the best as it significantly reduced the diamondback moth (DBM)
      (~60%) and aphid population (~70%) besides giving the highest yield (170%
      increase over control).

PMID- 25384369
TI  - Assessing the environmental genotoxicity risk in the Baltic Sea: frequencies of
      nuclear buds in blood erythrocytes of three native fish species.
AB  - Nuclear bud (NB) formation was investigated in blood erythrocytes of 1892
      flounder Platichthys flesus, herring Clupea harengus, and eelpout Zoarces
      viviparus specimens that were collected at 82 sites representing different
      regions of the Baltic Sea in 2009-2011. This is the first attempt to evaluate the
      baseline levels of NB and rank the genotoxicity risk for native fish species. NB
      levels were compared to the previously published micronuclei (MN) data from the
      same individual fish specimens in order to compare the two methods of
      genotoxicity assessment and investigate the relationship between MN as the
      cytogenetic measure of genotoxicity and the DNA damage reflecting NB. In 2009
      2011, elevated NB levels in 89.4% of flounder sampling groups indicated high and
      extremely high genotoxicity risk levels. Herring and eelpout sampling groups
      showed elevated levels of NB, 74.6 and 45.7%, respectively. In general, herring
      and eelpout NB measure was more sensitive as the genotoxicity biomarker than MN.

PMID- 25384370
TI  - Microbial and genetic ecology of tropical Vertisols under intensive chemical
      farming.
AB  - There are continued concerns on unscientific usage of chemical fertilizers and
      pesticides, particularly in many developing countries leading to adverse
      consequences for soil biological quality and agricultural sustainability. In
      farmers' fields in tropical Vertisols of peninsular India, "high" fertilizer and
      pesticide usage at about 2.3 times the recommended rates in black gram (Vigna
      mungo) did not have a deleterious effect on the abundance of culturable
      microorganisms, associative nitrogen fixers, nitrifiers, and 16S rRNA gene
      diversity compared to normal rates. However, "very high" application at about
      five times the fertilizers and 1.5 times pesticides in chilies (Capsicum annuum)
      adversely affected the populations of fungi, actinomycetes, and ammonifiers,
      along with a drastic change in the eubacterial community profile and diversity
      over normal rates. Actinobacteria were dominant in black gram normal (BG1) (47%),
      black gram high (BG2) (36%), and chili normal (CH1) (30%) and were least in chili
      very high (CH2) (14%). Geodermatophilus formed 20% of Actinobacteria in BG1 but
      disappeared in BG2, CH1, and CH2. Asticcacaulis dominated at "very high" input
      site (CH2). Diversity of nitrogen fixers was completely altered; Dechloromonas
      and Anaeromyxobacter were absent in BG1 but proliferated well in BG2. There was
      reduction in rhizobial nifH sequences in BG2 by 46%. Phylogenetic differences
      characterized by UniFrac and principal coordinate analysis showed that BG2 and
      CH2 clustered together depicting a common pattern of genetic shift, while BG1 and
      CH1 fell at different axis. Overall, there were adverse consequences of "very
      high" fertilizer and pesticide usage on soil microbial diversity and function in
      tropical Vertisols.

PMID- 25384371
TI  - Correspondence of biological condition models of California streams at statewide
      and regional scales.
AB  - We used boosted regression trees (BRT) to model stream biological condition as
      measured by benthic macroinvertebrate taxonomic completeness, the ratio of
      observed to expected (O/E) taxa. Models were developed with and without exclusion
      of rare taxa at a site. BRT models are robust, requiring few assumptions compared
      with traditional modeling techniques such as multiple linear regression. The BRT
      models were constructed to provide baseline support to stressor delineation by
      identifying natural physiographic and human land use gradients affecting stream
      biological condition statewide and for eight ecological regions within the state,
      as part of the development of numerical biological objectives for California's
      wadeable streams. Regions were defined on the basis of ecological, hydrologic,
      and jurisdictional factors and roughly corresponded with ecoregions.
      Physiographic and land use variables were derived from geographic information
      system coverages. The model for the entire state (n = 1,386) identified a
      composite measure of anthropogenic disturbance (the sum of urban, agricultural,
      and unmanaged roadside vegetation land cover) within the local watershed as the
      most important variable, explaining 56% of the variance in O/E values. Models for
      individual regions explained between 51 and 84% of the variance in O/E values.
      Measures of human disturbance were important in the three coastal regions. In the
      South Coast and Coastal Chaparral, local watershed measures of urbanization were
      the most important variables related to biological condition, while in the North
      Coast the composite measure of human disturbance at the watershed scale was most
      important. In the two mountain regions, natural gradients were most important,
      including slope, precipitation, and temperature. The remaining three regions had
      relatively small sample sizes (n <= 75 sites) and had models that gave mixed
      results. Understanding the spatial scale at which land use and land cover affect
      taxonomic completeness is imperative for sound management. Our results suggest
      that invertebrate taxonomic completeness is affected by human disturbance at the
      statewide and regional levels, with some differences among regions in the
      importance of natural gradients and types of human disturbance. The construction
      and application of models similar to the ones presented here could be useful in
      the planning and prioritization of actions for protection and conservation of
      biodiversity in California streams.

PMID- 25384372
TI  - Oxidative stress, glutathione level and antioxidant response to heavy metals in
      multi-resistant pathogen, Candida tropicalis.
AB  - In this study, we explored the multiple heavy metal-resistant yeast isolated from
      heavy metal-polluted environment. The isolated yeast showed maximum growth at 30 
      degrees C, pH 7.0, and the strain was identified as Candida tropicalis through
      18S ribosomal RNA (rRNA) gene sequence analysis. Yeast cells grew well in medium
      containing different concentrations of heavy metal ions [CdCl2, Pb(NO3)2, NaAsO2,
      CuSO4 and K2Cr2O7]. Minimum inhibitory concentration (MIC) against different
      metal ions was ranged from 5 to 19 mM, and the metal resistance value against
      each metal observed by yeast cells was 5 mM (Cr), 10 mM (Cd), 15 mM (As), 14 mM
      (Cu) and 19 mM (Pb) and increased in the following order: Pb > Cu > As >= Cd >
      Cr. The total cellular glutathione, GSH/GSSG redox couple and metallothioneins
      like protein (MT) were assayed by growing cultures for 24 h and exposed to 100
      mg/L of each heavy metal ion. Remarkable increase in gamma
      glutamylcysteinylglycine (GSH) level was determined in arsenic and cadmium
      treatment followed by chromium, lead and copper. Stressed cells had much more
      oxidized GSH than unstressed cells. GSH/GSSG ratio was significantly increased in
      cadmium and copper treatment in contrast to chromium, arsenic and lead.
      Statistical analysis revealed significantly higher cysteine level in all metal
      treated samples as compared to control. Antioxidant glutathione transferase
      activity was not detected in metal-treated and untreated yeast samples. One
      dimensional electrophoresis of proteins revealed marked differences in banding
      pattern of heavy metal-exposed yeast samples. A prominent 20 kDa band was
      observed in all treated samples suggesting that some differential proteins could
      be over-expressed during heavy metal treatment and might be involved in cell
      resistance mechanisms.

PMID- 25384373
TI  - Heavy metals fractionation in surface sediments of Gowatr bay--Iran.
AB  - In this study, the chemical speciation of heavy metals and their distribution in
      surface sediments of Gowatr bay, southeast Iran, are investigated. Modified
      Bureau Commune de Reference of the European Commission (BCR) sequential
      extraction technique was applied to assess Cu, Pb, Zn, Mn, Ni, Co, Cr, V, and Fe
      in the four fractions of five surface sediment samples. Calculated contamination
      factors (C(i)f) indicate considerable to very high degree of contamination for Cu
      and Cr, and very high degree for Zn and Ni. Maximum contamination degree (Cd)
      also suggests serious anthropogenic pollution at two sites. The dominance of
      average concentration of Cu, Pb, Zn, and Mn in non-residual fractions indicates
      higher ecological risk within Gowatr bay. Conversely, Ni, Co, Cr, Fe, and V
      mainly exist in residual phase and hence pose no immediate ecological risk.
      Calculated individual contamination factors (ICFs) indicate the highest risk of
      Cu, Pb, Zn, and Mn at two investigated sites. Global contamination factor (GCF)
      reveals that Pasabandar harbor is highly impacted by metal pollutants.

PMID- 25384374
TI  - Determination of bismuth in environmental samples by slurry sampling graphite
      furnace atomic absorption spectrometry using combined chemical modifiers.
AB  - Slurry sampling graphite furnace atomic absorption spectrometry technique was
      applied for the determination of Bi in environmental samples. The study focused
      on the effect of Zr, Ti, Nb and W carbides, as permanent modifiers, on the Bi
      signal. Because of its highest thermal and chemical stability and ability to
      substantially increase Bi signal, NbC was chosen as the most effective modifier.
      The temperature programme applied for Bi determination was optimized based on the
      pyrolysis and atomization curves obtained for slurries prepared from certified
      reference materials (CRMs) of the soil and sediments. To overcome interferences
      caused by sulfur compounds, Ba(NO3)2 was used as a chemical modifier. Calibration
      was performed using the aqueous standard solutions. The analysis of the CRMs
      confirmed the reliability of the proposed analytical method. The characteristic
      mass for Bi was determined to be 16 pg with the detection limit of 50 ng/g for
      the optimized procedure at the 5% (w/v) slurry concentration.

PMID- 25384376
TI  - Plasma homocysteine but not MTHFR gene polymorphism is associated with geriatric
      depression in the Chinese population.
AB  - BACKGROUND: Epidemiological studies suggested that elevated plasma homocysteine
      (Hcy) is associated with an increased risk of depression and cerebrovascular
      disease (CVD). There were few published reports of Hcy levels and
      methylenetetrahydrofolate reductase (MTHFR) C677T genotype in geriatric
      depression. OBJECTIVE: To investigate the relationship among plasma Hcy level,
      MTHFR C677T polymorphism and geriatric depression in the Chinese population.
      METHODS: The plasma Hcy level measured by capillary electrophoresis with
      ultraviolet detection and the C667T polymorphism of MTHFR detected using
      polymerase chain reaction-restriction fragment length polymorphism assay were
      determined in 116 patients with geriatric depression and in 80 healthy controls.
      RESULTS: The plasma Hcy level in the patients with geriatric depression was
      significantly higher than that in controls (p < 0.001). The age of first episode
      and comorbid CVD were significantly correlated with plasma Hcy levels in
      geriatric patients (p = 0.014 and 0.008, respectively). The Hamilton Rating Scale
      for Depression total score and plasma Hcy level at baseline showed no significant
      correlation in the patients (r = -0.111, p = 0.397). There were no significant
      differences in the MTHFR C677T polymorphism genotypes and alleles between the
      patients and the healthy controls (p = 0.654 and 0.573, respectively).
      CONCLUSION: The elevated plasma Hcy level is a risk factor for geriatric
      depression. MTHFR C667T genotype is not associated with geriatric depression in
      the Chinese population.

PMID- 25384375
TI  - Continued loss in visceral and intermuscular adipose tissue in weight-stable
      women following bariatric surgery.
AB  - OBJECTIVE: To assess changes in total (TAT), subcutaneous (SAT), visceral (VAT),
      and intermuscular (IMAT) adipose tissue by whole-body MRI before surgery and at
      12 months and 24 months post-surgery in a subset of participants of the
      Longitudinal Assessment of Bariatric Surgery-2. METHODS: From 0 to 12 months, n =
      20 females and 3 males; from 12 to 24 months, n = 42 females and 7 males. Paired
      t-tests and GLM repeated measures examined changes in TAT, SAT, VAT, and IMAT at
      12 and 24 months, with sex and age as covariates. RESULTS: Changes from 0 to 12
      months included weight (-41.9 +/- 12.1 kg; -36%), TAT (-33.5 +/- 9.6 kg; -56%),
      SAT (-29.2 +/- 8.2 kg; -55%), VAT (-3.3 +/- 1.6 kg; -73%), and IMAT (-0.99 +/-
      0.68 kg; -50%), all P < 0.001. In females, from 12 to 24 months, despite relative
      weight stability (-1.8 +/- 6.5 kg, -2%; P = 0.085), VAT (-0.5 +/- 0.7 kg; -30%; P
      < 0.001) and IMAT (-0.2 +/- 0.4 kg; -14%; P = 0.012) decreased further. In males,
      from 12 to 24 months, weight increased (5.1 +/- 5.2 kg; 6%; P = 0.04) with no
      significant changes in TAT or sub-depots. CONCLUSIONS: Bariatric surgery
      continues to induce favorable changes in body composition, i.e., persistent
      adipose tissue loss at 24 months in the absence of further significant weight
      loss.

PMID- 25384377
TI  - Stroke with supernumerary phantom limb: case study, review of literature and
      pathogenesis.
AB  - OBJECTIVE: Constitute hypothesis for origin of supernumerary phantom limb (SPL)
      after stroke. METHOD: Single case description, review of literature and
      formulation of hypothesis. RESULTS: A 59-year-old lady was evaluated for
      complaints of left-sided hemiparesis and extra limbs attached to her left
      shoulder for the past 7 months. Neuropsychological assessment revealed left
      hemineglect with SPL, and profile suggested bilateral frontal, right
      parietotemporal and basal ganglia involvement. Magnetic resonance imaging brain
      scan showed gliotic cavity secondary to the old haematoma in right putamen with
      white matter changes in the right frontoparietotemporal lobes. CONCLUSIONS: The
      conceptual framework of body schema can be used to classify many of the
      neurological disorders of body representation. Generation of SPL comes under the
      subtype of pathology of updating among the disorders of body schema. The
      continuous updating allows the body schema to modulate perceptual processing of
      objects according to their position in space. Brain areas classified as parts of
      motor system can, under pathological conditions (haemorrhage), influence body
      perception. So, when she used to move her arm, the representation of the
      estimated position was not updated by the motor commands. Sensory and motor
      information therefore becomes discrepant, and failure to integrate these two
      sources of information leads to loss of normal coherence, and the perceived shape
      of the body was altered by adding a SPL to accommodate the discrepancy.

PMID- 25384378
TI  - Verbal working memory deficits in abstinent heroin abusers.
AB  - BACKGROUND: A prevailing belief is that opioids tend not to impair cognitive
      performance in opioid-dependent users. However, the impact of heroin abuse on
      verbal memory, especially on working memory, is not well studied and the results
      available are inconsistent. OBJECTIVE: This study was carried out to test the
      hypothesis that abstinent heroin abusers have intact working memory capacity.
      METHODS: N-back task and backward digit span task were used to measure the verbal
      working memory capacity in 28 abstinent heroin abusers and 25 controls matched
      for age, education level and gender. Forward digit span task was used as a
      control task to measure short-term memory capacity. RESULTS: Compared with the
      control subjects, heroin abusers showed normal backward/forward digit spans but
      significant performance impairment in the n-back task. CONCLUSION: Abstinent
      heroin abusers have intact short-term memory capacity but impaired verbal working
      memory capacity.

PMID- 25384379
TI  - Relationship between preferred sleeping position and unilateral disc haemorrhage
      in normal-tension glaucoma patients.

PMID- 25384380
TI  - Hormonal receptors and vascular endothelial growth factor in juvenile
      nasopharyngeal angiofibroma: immunohistochemical and tissue microarray analysis.
AB  - CONCLUSION: This work demonstrated that juvenile nasopharyngeal angiofibromas
      (JNAs) express high levels of hormone receptors and vascular endothelial growth
      factor (VEGF) compared with normal nasal mucosa. The interaction between hormone
      receptors and VEGF may be involved in the initiation and growth of JNA.
      OBJECTIVES: JNA is a rare benign tumor that occurs almost exclusively in male
      adolescents. Although generally regarded as a hormone-dependent tumor, this has
      not been proven in previous studies. The aim of this study was to investigate the
      role of hormone receptors in JNA and the relationship with clinical
      characteristics. METHODS: Standard immunohistochemical microarray analysis was
      performed on 70 JNA samples and 10 turbinate tissue samples. Specific antibodies
      for androgen receptor (AR), estrogen receptor-alpha (ER-alpha), estrogen receptor
      beta (ER-beta), progesterone receptor (PR), and VEGF were examined, and the
      relationships of receptor expression with age, tumor stage, and bleeding were
      evaluated. RESULTS: RESULTS showed that JNA expressed ER-alpha (92.9%), ER-beta
      (91.4%), AR (65.7%), PR (12.8%), and VEGF (95.7%) at different levels. High level
      of VEGF was linked to elevated ER-alpha and ER-beta. There was no significant
      relationship between hormonal receptors and age at diagnosis, tumor stage or
      bleeding. However, overexpression of ER-alpha was found to be an indicator of
      poor prognosis (p = 0.031).

PMID- 25384381
TI  - The effect of the prone sleeping position on obstructive sleep apnoea.
AB  - CONCLUSIONS: Prone positioning reveals promising results in improving the apnoea
      hypopnoea index (AHI) and oxygen desaturation index (ODI) in patients with
      obstructive sleep apnoea (OSA). OBJECTIVE: To evaluate the effect of the prone
      position on OSA. METHODS: Thirty-two patients with mild to severe OSA were
      included in the study. This was a two-night study to evaluate the effect of the
      prone position on OSA; a first night in a normal bed with optional positioning
      and a second night on a mattress and pillow facilitating prone positioning.
      RESULTS: A total of 27 patients, 22 males and 5 females, with a mean age of 51
      years, 15 patients with positional OSA (POSA) and 12 patients with non-POSA with
      a total median AHI of 23 (min 5, max 93) completed the study protocol. The median
      AHI decreased from 23 to 7 (p < 0.001) and the median ODI from 21 to 6 (p <
      0.001). The median time spent in the supine position decreased from 142 to <1 min
      (p < 0.0001) and the median time in the prone position increased from <1 to 330
      min (p < 0.0001). In all, 17 of 27 patients (63%) were considered to be
      responders to prone positioning, 12 of 15 (80%) with POSA and 5 of 12 (42%) with
      non-POSA. Five patients did not complete the study protocol due to sleep time <4
      h.

PMID- 25384382
TI  - Soybean and Fish Oil Mixture With Different omega-6/omega-3 Polyunsaturated Fatty
      Acid Ratios Modulates Dextran Sulfate Sodium-Induced Changes in Small Intestinal
      Intraepithelial gammadeltaT-Lymphocyte Expression in Mice.
AB  - BACKGROUND: This study investigated the effect of different omega-6/omega-3
      polyunsaturated fatty acid (PUFA) ratios on dextran sulfate sodium (DSS)-induced
      changes to small intestinal intraepithelial lymphocyte (IEL) gammadeltaT-cell
      expression. METHODS: Mice were assigned to 3 control and 3 DSS-treated groups and
      were maintained on a low-fat semipurified diet. One of the control (S) groups and
      a DSS (DS) group were provided with soybean oil; the other 2 control (Homega-3
      and Lomega-3) groups and 2 other DSS (DHomega-3 and DLomega-3) groups were fed
      either a soybean and fish oil mixture with a omega-6/omega-3 ratio of 2:1 or 4:1.
      After feeding the respective diets for 2 weeks, the DSS groups were given
      distilled water containing 2% DSS, and the control groups were given distilled
      water for 5 days. All groups were further provided distilled water 5 days for
      recovery, and the small intestinal IEL gammadeltaT-cell subset was isolated for
      analysis. RESULTS: DSS treatment resulted in a lower small intestinal IEL
      gammadeltaT-cell percentage and higher messenger RNA (mRNA) expressions of Reg
      IIIgamma, keratinocyte growth factor (KGF), and complement 5a receptor (C5aR) by
      IEL gammadeltaT cells. Fish oil administration enhanced the proportion of small
      intestinal IEL gammadeltaT cells. Compared with the DLomega-3 group, the DHomega
      3 group had lower Reg IIIgamma, KGF, and C5aR mRNA expressions and higher
      expression of peroxisome proliferator-activated receptor (PPAR)-gamma gene by
      small intestinal IEL gammadeltaT cells. CONCLUSIONS: Fish oil diets with a omega
      6/omega-3 PUFA ratio of 2:1 were more effective than those with a ratio of 4:1 in
      improving DSS-induced small intestinal injury, and activation of PPAR-gamma in
      IEL gammadeltaT cells may be associated with resolution of small intestinal
      inflammation.

PMID- 25384384
TI  - Toxic detection in mine water based on proteomic analysis of lysosomal enzymes in
      Saccharomyces cerevisiae.
AB  - OBJECTIVES: Lysosome is the cell-organelle which is commonly used as
      biomonitoring tool in environmental pollution. In this study, the lysosomal
      proteomic of the yeast Saccharomyces cerevisiae was analyzed for utilization in
      the detection of toxic substances in mine water samples. METHODS: This work
      informs the expression of lysosomal proteomic in yeast in response with toxic
      chemicals, such as sodium meta-arsenite and tetracycline, for screening specific
      biomarkers. After that, a recombinant yeast contained this biomarker were
      constructed for toxic detection in pure toxic chemicals and mine water samples.
      RESULTS: Each chemical had an optimal dose at which the fluorescent protein
      intensity reached the peak. In the case of water samples, the yeast showed the
      response with sample 1, 3, 4, and 5; whereas there is no response with sample 2,
      6, and 7. CONCLUSIONS: The recombinant yeast showed a high ability of toxic
      detection in response with several chemicals such as heavy metals and
      pharmaceuticals. In the case of mine water samples, the response varied depending
      on the sample content.

PMID- 25384383
TI  - AMACR amplification in myxofibrosarcomas: a mechanism of overexpression that
      promotes cell proliferation with therapeutic relevance.
AB  - PURPOSE: Myxofibrosarcomas frequently display arm-level gains on 5p. We
      characterized the pathogenetic and therapeutic relevance of the alpha-methylacyl
      coenzyme A racemase (AMACR) at 5p13.3. EXPERIMENTAL DESIGN: AMACR mRNA expression
      in myxofibrosarcomas was analyzed using the public transcriptome and laser
      microdissected sarcoma cells. We performed florescence in situ hybridization
      (FISH) and immunohistochemistry in independent samples for clinical correlates.
      In AMACR-overexpressing myxofibrosarcoma cells and xenografts, we elucidated the
      biologic function of AMACR using RNA interference and explored the therapeutic
      effect and mechanism of an AMACR inhibitor, ebselen oxide. RESULTS: AMACR protein
      overexpression and gene amplification were significantly associated with each
      other (P < 0.001), with higher tumor grades (both P <= 0.002), and univariately
      with worse metastasis-free survival (MFS; both P < 0.0001) and disease-specific
      survival (DSS; P = 0.0002 for overexpression; P = 0.0062 for amplification).
      AMACR protein overexpression also independently portended adverse outcome (DSS, P
      = 0.007; MFS, P = 0.001). However, 39% of AMACR-overexpression cases did not show
      gene amplification, implying alternative regulatory mechanisms. In
      myxofibrosarcoma cell lines, stable AMACR knockdown suppressed cell
      proliferation, anchorage-independent growth, and expression of cyclin D1 and
      cyclin T2. These growth-promoting attributes of AMACR were corroborated in the
      AMACR-silenced xenograft model and AMACR-underexpressed myxofibrosarcomas,
      showing decreased labeling for cyclin D1, cyclin T2, and Ki-67. Compared with
      fibroblasts, AMACR-expressing myxofibrosarcoma cells were more susceptible to
      ebselen oxide, which not only decreased viable cells, promoted proteasome
      mediated degradation of AMACR protein, and induced cellular apoptosis in vitro,
      but also dose-dependently suppressed xenografted tumor growth in vivo.
      CONCLUSIONS: Overexpressed AMACR in myxofibrosarcomas can be amplification
      driven, associated with tumor aggressiveness, and may be relevant as a druggable
      target.

PMID- 25384385
TI  - The separation of arsenic metabolites in urine by high performance liquid
      chromatographyinductively coupled plasma-mass spectrometry.
AB  - OBJECTIVES: The purpose of this study was to determine a separation method for
      each arsenic metabolite in urine by using a high performance liquid
      chromatography (HPLC)- inductively coupled plasma-mass spectrometer (ICP-MS).
      METHODS: Separation of the arsenic metabolites was conducted in urine by using a
      polymeric anion-exchange (Hamilton PRP X-100, 4.6 mm*150 mm, 5 MUm) column on
      Agilent Technologies 1260 Infinity LC system coupled to Agilent Technologies 7700
      series ICP/MS equipment using argon as the plasma gas. RESULTS: All five
      important arsenic metabolites in urine were separated within 16 minutes in the
      order of arsenobetaine, arsenite, dimethylarsinate, monomethylarsonate and
      arsenate with detection limits ranging from 0.15 to 0.27 MUg/L (40 MUL
      injection). We used GEQUAS No. 52, the German external quality assessment scheme
      and standard reference material 2669, National Institute of Standard and
      Technology, to validate our analyses. CONCLUSIONS: The method for separation of
      arsenic metabolites in urine was established by using HPLC-ICP-MS. This method
      contributes to the evaluation of arsenic exposure, health effect assessment and
      other bio-monitoring studies for arsenic exposure in South Korea.

PMID- 25384386
TI  - Nanometrology and its perspectives in environmental research.
AB  - OBJECTIVES: Rapid increase in engineered nanoparticles (ENPs) in many goods has
      raised significant concern about their environmental safety. Proper methodologies
      are therefore needed to conduct toxicity and exposure assessment of nanoparticles
      in the environment. This study reviews several analytical techniques for
      nanoparticles and summarizes their principles, advantages and disadvantages,
      reviews the state of the art, and offers the perspectives of nanometrology in
      relation to ENP studies. METHODS: Nanometrology is divided into five techniques
      with regard to the instrumental principle: microscopy, light scattering,
      spectroscopy, separation, and single particle inductively coupled plasma-mass
      spectrometry. RESULTS: Each analytical method has its own drawbacks, such as
      detection limit, ability to quantify or qualify ENPs, and matrix effects. More
      than two different analytical methods should be used to better characterize ENPs.
      CONCLUSIONS: In characterizing ENPs, the researchers should understand the
      nanometrology and its demerits, as well as its merits, to properly interpret
      their experimental results. Challenges lie in the nanometrology and pretreatment
      of ENPs from various matrices; in the extraction without dissolution or
      aggregation, and concentration of ENPs to satisfy the instrumental detection
      limit.

PMID- 25384387
TI  - House-plant placement for indoor air purification and health benefits on
      asthmatics.
AB  - OBJECTIVES: Some plants were placed in indoor locations frequented by asthmatics
      in order to evaluate the quality of indoor air and examine the health benefits to
      asthmatics. METHODS: The present study classified the participants into two
      groups: households of continuation and households of withdrawal by a quasi
      experimental design. The households of continuation spent the two observation
      terms with indoor plants, whereas the households of withdrawal passed the former
      observation terms with indoor plants and went through the latter observation term
      without any indoor plants. RESULTS: The household of continuation showed a
      continual decrease in the indoor concentrations of volatile organic compounds
      (VOCs) during the entire observation period, but the household of withdrawal
      performed an increase in the indoor concentrations of VOCs, except formaldehyde
      and toluene during the latter observation term after the decrease during the
      former observation term. Peak expiratory flow rate (PEFR) increased in the
      households of continuation with the value of 13.9 L/min in the morning and 20.6
      L/ min in the evening, but decreased in the households of withdrawal with the
      value of -24.7 L/min in the morning and -30.2 L/min in the evening in the first
      experimental season. All of the households exhibited a decrease in the value of
      PEFR in the second experimental season. CONCLUSIONS: Limitations to the
      generalizability of findings regarding the presence of plants indoors can be seen
      as a more general expression of such a benefit of human-environment relations.

PMID- 25384388
TI  - Risk and culture: variations in dioxin risk perceptions, behavioral preferences
      among social groups in South Korea.
AB  - OBJECTIVES: This study examined variations in the perceptions of dioxin risk
      among social groups defined by geographical living location, environmental
      education, and occupation. Dioxin risk perceptions were analyzed according to
      values, risk awareness, knowledge, and behavioral preferences. METHODS: A quasi
      experimental survey was designed and conducted on individuals from seven
      experimental groups in Jeonju city, South Korea, including: people living near
      incineration facilities; people living far from incineration facilities;
      governmental experts; nongovernmental organization members; office workers in
      developmental institutes or banks; students who were enrolled in environmental
      related classes; and students who were enrolled in business-related classes.
      RESULTS: The results show variations among groups in values, awareness and
      behavioral preferences. Particular attention should be given to the result that
      groups with higher connectedness- to-nature values show higher willingness-to-act
      (WTA) for risk reduction. Result s can be summarized as follows. First, awareness
      is associated with one's geographical setting. Second, values and WTA behaviors
      are related to one's environmental-related education and occupation. Third,
      values are significantly related to WTA behaviors. CONCLUSIONS: Different
      cultures, in terms of values or worldview, among groups influence their
      perceptions of dioxin risk and choices of risk reduction behaviors. It is
      important to consider values in communicating complicated long-term risk
      management involving public participation. Further research should be
      continuously conducted on the effects of multiple dimensions of values on one's
      WTA for risk reduction behaviors.

PMID- 25384389
TI  - How will we know if Obamacare has "worked"?

PMID- 25384390
TI  - Effects of number, complexity, and familiarity of flankers on crowded letter
      identification.
AB  - We tested identification of target letters surrounded by a varying number (2, 4,
      6) of horizontally aligned flanking elements. Strings were presented left or
      right of a central fixation dot, and targets were always at the center of the
      string. Flankers could be other letters, digits, symbols, simple shapes, or false
      fonts, and thus varied both in terms of visual complexity and familiarity. Two
      alternative forced choice (2AFC) speed and accuracy was measured for choosing the
      target letter versus an alternative letter that was not present in the string.
      Letter identification became harder as the number of flankers increased. Greater
      flanker complexity led to more interference in target identification, whereas
      more complex targets were easier to identify. Effects of flanker complexity were
      found to depend on visual field and position of flankers, with the strongest
      effects seen for leftward flankers in the left visual field. Visual complexity
      predicted flanker interference better than familiarity, and better than target
      flanker similarity. These results provide further support for an excessive
      feature-integration account of the interfering effects of both adjacent and
      nonadjacent flanking elements in horizontally aligned strings. 

PMID- 25384391
TI  - Comparison of two fixation methods for arthrodesis of the calcaneocuboid joint: a
      biomechanical study.
AB  - BACKGROUND: The traditional fixation for a calcaneocuboid (CC) arthrodesis in
      triple arthrodesis is with a 6.5-mm cancellous screw. This procedure can be
      technically challenging. Fixation with a locking compression plate (LCP) may be
      easier to perform while achieving compression perpendicular to the fusion site.
      The purpose of this study was to compare the load to failure and the stiffness
      for each fixation method. METHODS: Five matched-pair cadaver feet had an
      arthrodesis of the CC joint. For each matched pair, one was fixed with a screw
      and the other with an LCP. Surface bead markers were applied. Each specimen was
      then secured to a material testing machine through the calcaneus. The plantar
      surface of the cuboid faced the hydraulic ram to simulate weightbearing. A force
      was applied while the specimen was recorded with a high-resolution camera. The
      endpoint was maximal force at 2-mm separation between the calcaneus and cuboid
      measured along a horizontal axis. RESULTS: The average force to failure and the
      average stiffness in the screw group were significantly less than the LCP group
      (P < .05). The screw construct failed in pullout from the cuboid; the LCP
      construct failed by plastic deformation of the plate. CONCLUSION: Calcaneocuboid
      joint fixation with the LCP withstood a higher load until failure and
      demonstrated greater stiffness than with a 6.5-mm cancellous lag screw. CLINICAL
      RELEVANCE: The use of LCP fixation can be considered as an alternative to oblique
      lag screw fixation for CC arthrodesis in a triple arthrodesis. It remains to be
      determined if LCP fixation leads to better clinical outcomes.

PMID- 25384392
TI  - Tau deletion impairs intracellular beta-amyloid-42 clearance and leads to more
      extracellular plaque deposition in gene transfer models.
AB  - BACKGROUND: Tau is an axonal protein that binds to and regulates microtubule
      function. Hyper-phosphorylation of Tau reduces its binding to microtubules and it
      is associated with beta-amyloid deposition in Alzheimer's disease. Paradoxically,
      Tau reduction may prevent beta-amyloid pathology, raising the possibility that
      Tau mediates intracellular Abeta clearance. The current studies investigated the
      role of Tau in autophagic and proteasomal intracellular Abeta1-42 clearance and
      the subsequent effect on plaque deposition. RESULTS: Tau deletion impaired Abeta
      clearance via autophagy, but not the proteasome, while introduction of wild type
      human Tau into Tau-/- mice partially restored autophagic clearance of Abeta1-42,
      suggesting that exogenous Tau expression can support autophagic Abeta1-42
      clearance. Tau deletion impaired autophagic flux and resulted in Abeta1-42
      accumulation in pre-lysosomal autophagic vacuoles, affecting Abeta1-42 deposition
      into the lysosome. This autophagic defect was associated with decreased
      intracellular Abeta1-42 and increased plaque load in Tau-/- mice, which displayed
      less cell death. Nilotinib, an Abl tyrosine kinase inhibitor that promotes
      autophagic clearance mechanisms, reduced Abeta1-42 only when exogenous human Tau
      was expressed in Tau-/- mice. CONCLUSIONS: These studies demonstrate that Tau
      deletion affects intracellular Abeta1-42 clearance, leading to extracellular
      plaque.

PMID- 25384393
TI  - Factors associated with daily tenofovir exposure in Thai subjects taking
      combination antiretroviral therapy.
AB  - Tenofovir (TFV) exposure is associated with antiretroviral efficacy and risk of
      kidney disease. There is evidence of high interindividual variability of the
      pharmacokinetics of TFV. The effect of several clinical conditions on the
      pharmacokinetics of TFV has been observed and may partly explain its variability.
      We assessed factors influencing the pharmacokinetics of TFV in Thai patients.
      Thirty participants (50% female) taking efavirenz- or ritonavir-boosted protease
      inhibitor-based regimens were investigated. Intensive pharmacokinetic sampling
      was performed over 24 h. Multivariate geometric mean regression models adjusted
      for covariates with p <= 0.2 in univariate analysis were developed. The median
      age was 41 years. Five participants [three taking a protease inhibitor (PI) and
      two taking efavirenz (EFV)] had mild renal dysfunction [estimated glomerular
      filtration rate (eGFR) 60-90 ml/min/1.73 m(2); range 72-89]. TFV AUC0-24 was 23%
      (95% CI 1-49%; p=0.04) higher in those taking PI vs. EFV, 39% (95% CI 5-84%;
      p=0.02) higher in those with mild renal dysfunction, and reduced by 16% (95% CI 5
      26%; p=0.008) with each 10 kg body weight increase, after adjusting for sex and
      duration of TFV exposure. In PI-treated subjects TFV AUC0-24 increased by 3% (0.3
      6%; p=0.03) for each mg.h/liter increase in ritonavir (RTV) AUC0-24 after
      adjusting for sex, weight, mild renal impairment, and proximal renal tubular
      dysfunction. Significantly higher TFV exposures were independently associated
      with PI regimens, mild renal impairment, lower body weight, and increasing RTV
      AUC0-24. Clinicians should be aware of the effect of these factors on TFV
      exposure when this drug is prescribed.

PMID- 25384395
TI  - Successful switch to dabrafenib after vemurafenib-induced toxic epidermal
      necrolysis.

PMID- 25384396
TI  - Factors associated with the intention of health care personnel to respond to a
      disaster.
AB  - INTRODUCTION: Over the past decade, numerous groups of researchers have studied
      the willingness of health care personnel (HCP) to respond when a disaster
      threatens the health of a community. Not one of those studies reported that 100%
      of HCP were willing to work during a public-health event (PHE). PROBLEM: The
      objective of this study was to explore factors associated with the intent of HCP
      to respond to a future PHE. METHODS: The theory of planned behavior (TPB) framed
      this cross-sectional study. Data were obtained via a web-based survey from 305
      HCP. Linear associations between the TPB-based predictor and outcome variables
      were examined using Pearson's correlations. Differences between two groups of HCP
      were calculated using independent t tests. A model-generating approach was used
      to develop and assess a series of TBP-based observed variable structural equation
      models for prediction of intent to respond to a future PHE and to explore
      moderating and mediating effects. RESULTS: The beginning patterns of
      relationships identified by the correlation matrix and t tests were evident in
      the final structural equation model, even though the patterns of prediction
      differed from those posited by the theory. Outcome beliefs had both a
      significant, direct effect on intention and an indirect effect on intention that
      was mediated by perceived behavioral control. Control beliefs appeared to
      influence intention through perceived behavioral control, as posited by the TPB,
      and unexpectedly through subjective norm. Subjective norm not only mediated the
      relationship between control beliefs and intention, but also the relationship
      between referent beliefs and intention. Additionally, professional affiliation
      seemed to have a moderating effect on intention. CONCLUSION: The intention to
      respond was influenced primarily by normative and control factors. The intent of
      nurses to respond to a future PHE was influenced most by the control factors,
      whereas the intent of other HCP was shaped more by the normative factors. Health
      care educators can bolster the normative and control factors through education by
      focusing on team building and knowledge related to accessing supplies and support
      needed to respond when a disaster occurs.

PMID- 25384394
TI  - Pseudomonas 2.0: genetic upgrading of P. putida KT2440 as an enhanced host for
      heterologous gene expression.
AB  - BACKGROUND: Because of its adaptability to sites polluted with toxic chemicals,
      the model soil bacterium Pseudomonas putida is naturally endowed with a number of
      metabolic and stress-endurance qualities which have considerable value for
      hosting energy-demanding and redox reactions thereof. The growing body of
      knowledge on P. putida strain KT2440 has been exploited for the rational design
      of a derivative strain in which the genome has been heavily edited in order to
      construct a robust microbial cell factory. RESULTS: Eleven non-adjacent genomic
      deletions, which span 300 genes (i.e., 4.3% of the entire P. putida KT2440
      genome), were eliminated; thereby enhancing desirable traits and eliminating
      attributes which are detrimental in an expression host. Since ATP and NAD(P)H
      availability - as well as genetic instability, are generally considered to be
      major bottlenecks for the performance of platform strains, a suite of functions
      that drain high-energy phosphate from the cells and/or consume NAD(P)H were
      targeted in particular, the whole flagellar machinery. Four prophages, two
      transposons, and three components of DNA restriction-modification systems were
      eliminated as well. The resulting strain (P. putida EM383) displayed growth
      properties (i.e., lag times, biomass yield, and specific growth rates) clearly
      superior to the precursor wild-type strain KT2440. Furthermore, it tolerated
      endogenous oxidative stress, acquired and replicated exogenous DNA, and survived
      better in stationary phase. The performance of a bi-cistronic GFP-LuxCDABE
      reporter system as a proxy of combined metabolic vitality, revealed that the
      deletions in P. putida strain EM383 brought about an increase of >50% in the
      overall physiological vigour. CONCLUSION: The rationally modified P. putida
      strain allowed for the better functional expression of implanted genes by
      directly improving the metabolic currency that sustains the gene expression flow,
      instead of resorting to the classical genetic approaches (e.g., increasing the
      promoter strength in the DNA constructs of interest).

PMID- 25384397
TI  - Magnetically tunable Mie resonance-based dielectric metamaterials.
AB  - Electromagnetic materials with tunable permeability and permittivity are highly
      desirable for wireless communication and radar technology. However, the
      tunability of electromagnetic parameters is an immense challenge for conventional
      materials and metamaterials. Here, we demonstrate a magnetically tunable Mie
      resonance-based dielectric metamaterials. The magnetically tunable property is
      derived from the coupling of the Mie resonance of dielectric cube and
      ferromagnetic precession of ferrite cuboid. Both the simulated and experimental
      results indicate that the effective permeability and permittivity of the
      metamaterial can be tuned by modifying the applied magnetic field. This mechanism
      offers a promising means of constructing microwave devices with large tunable
      ranges and considerable potential for tailoring via a metamaterial route. 

PMID- 25384398
TI  - S-nitrosothiols regulate nitric oxide production and storage in plants through
      the nitrogen assimilation pathway.
AB  - Nitrogen assimilation plays a vital role in plant metabolism. Assimilation of
      nitrate, the primary source of nitrogen in soil, is linked to the generation of
      the redox signal nitric oxide (NO). An important mechanism by which NO regulates
      plant development and stress responses is through S-nitrosylation, that is,
      covalent attachment of NO to cysteine residues to form S-nitrosothiols (SNO).
      Despite the importance of nitrogen assimilation and NO signalling, it remains
      largely unknown how these pathways are interconnected. Here we show that SNO
      signalling suppresses both nitrate uptake and reduction by transporters and
      reductases, respectively, to fine tune nitrate homeostasis. Moreover, NO derived
      from nitrate assimilation suppresses the redox enzyme S-nitrosoglutathione
      Reductase 1 (GSNOR1) by S-nitrosylation, preventing scavenging of S
      nitrosoglutathione, a major cellular bio-reservoir of NO. Hence, our data
      demonstrates that (S)NO controls its own generation and scavenging by modulating
      nitrate assimilation and GSNOR1 activity. 

PMID- 25384399
TI  - Ultrasonographic evaluation of sciatic nerves in patients with spinal cord
      injury.
AB  - STUDY DESIGN: Cross-sectional, controlled study. OBJECTIVE: To evaluate the
      sciatic nerves of subjects with spinal cord injury (SCI) by using ultrasound (US)
      imaging and to explore whether US measurements are associated with clinical and
      electrophysiological findings. SETTING: National Rehabilitation Center in Ankara,
      Turkey. METHODS: Fifteen SCI subjects (12 male (M), 3 female (F)) and 23 (16 M, 7
      F) healthy controls were included in the study. After clinical assessment of the
      subjects, lower limb nerve conduction studies and US imaging of the sciatic
      nerves were performed. Cross-sectional area (CSA) values of the sciatic nerves
      were correlated with the clinical and electrophysiologic data. RESULTS: Mean CSA
      values were lower in the patient group when compared with the control group
      (P=0.042). Reduced compound motor action potentials regarding tibial and peroneal
      nerves were observed in the patient group (P=0.003 and P=0.005, respectively). US
      measurements did not correlate with the electrophysiological findings. However,
      sciatic nerve CSA values were positively correlated with body mass index in the
      control (r=0.534, P<0.05) and patient (r=0.482, P<0.05) groups. CONCLUSION:
      Sciatic nerves seem to be smaller in subjects with SCI. Together with our
      electrophysiological data, this preliminary finding could possibly be attributed
      to primary axonal loss.

PMID- 25384400
TI  - A retrospective review of the ambulatory blood pressure patterns and diurnal
      urine production in subgroups of spinal cord injured patients.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVES: To quantify diurnal blood pressure
      (BP) patterns and nocturnal hypertension and to measure diurnal urine production
      in spinal cord injury (SCI) patients with clinically significant disorders of BP
      control. SETTING: A specialist state-based spinal cord service in Victoria,
      Australia. METHODS: Medical records of patients with traumatic SCI who were
      referred to a specialist service for management of a BP disorder were examined.
      Ambulatory BP and nocturnal urine production were compared between groups of
      patients classified according to level, completeness and chronicity of SCI.
      Patients with night:day systolic BP <90% were classified as dippers, 90-100% as
      non-dippers and >100% as reversed dippers. RESULTS: Patients (44 tetraplegic, 10
      paraplegic) were predominantly males (92.6%) aged 41+/-2.5 years (mean+/-s.e.m.).
      Referral was for orthostatic intolerance (n=37), autonomic dysreflexia (n=6),
      nocturnal polyuria (n=4), elevated BP (n=1) and peripheral oedema (n=1). The
      average BP was 111.1+/-1.4/65.0+/-1.2 mm Hg. In 56% of patients (n=30), BP at
      night was higher than during the day and another 37% (n=20) were non-dippers.
      Nocturnal hypertension was present in 31% (n=17) of the patients. In the
      tetraplegic patients, urine flow rate was greater during the night than day
      (121+/-9.5 ml h(-1) vs 89+/-8.2 ml h(-1), P=0.025). CONCLUSION: Ambulatory BP
      monitoring in patients with SCI and clinically significant BP disorders detected
      a high incidence of reversed dipping and nocturnal hypertension. We postulate
      elevated nocturnal BP may contribute to nocturnal diuresis that might cause
      relative volume depletion and thereby contribute to daytime orthostatic
      hypotension.

PMID- 25384401
TI  - Design and analysis of a new medial reciprocal linkage using a lower limb
      paralysis simulator.
AB  - STUDY DESIGN: A feasibility study on the effect of a new reciprocating orthosis
      on specific gait parameters for use by people with spinal cord injury.
      OBJECTIVES: The aim of this study was to design and develop a new medial linkage
      orthosis (MLO) mechanism incorporating a reciprocating motion and to determine
      its efficacy in improving specific spatiotemporal, kinematic and kinetic
      parameters while ambulating when worn by healthy subjects. This was achieved via
      the use of a lower limb paralysis simulator (LLPS). METHODS: A reciprocating
      joint with a remote center of motion was designed for use as an MLO. A prototype
      was fabricated and incorporated into an orthosis and equipped with a saddle to
      make the reciprocating motion possible. The efficacy of the orthosis was
      evaluated on four able-bodied healthy subjects who were trained to walk with the
      MLO attached to the LLPS. RESULTS: Mean walking speed, stride length, stride time
      and cadence was 0.09+/-0.007 m s(-1), 0.42+/-0.01 m, 4.89+/-0.45 s and 29.54+/
      4.32 steps min(-1), respectively, when healthy subjects walked with the new
      orthosis. The mean hip joint torque produced was 0.36+/-0.13 Nm. CONCLUSION: In
      this study a new MLO was designed and fabricated that provided a reciprocating
      mechanism using a four-bar mechanism to set the virtual axis of the mechanism in
      a more proximal position than hinge-type joints. Further investigation is
      currently underway to assess its effect on gait parameters and energy expenditure
      in paraplegic patients.

PMID- 25384402
TI  - Spinal sample showing p-JNK and P38 associated with the pain signaling
      transduction of glial cell in neuropathic pain.
AB  - OBJECTIVE: To investigate the signaling pathways after astrocytes were activated
      in neuropathic pain. METHODS: Thirty-six Sprague Dawley (s.d.) rats were randomly
      divided into two groups (each group with 18 s.d. rats) including chronic
      constriction injury (CCI) of the sciatic nerve model group and sham operation
      group. Operation was perform ed on the right leg in all rats. The lumbar spin al
      cord (L4 and L5) was taken to make paraffin slices on the 1st day before
      operation and the 1st, 3rd, 7th, 14th and 28th day after operation in each group.
      Paraffin slices were labeled with p38 mitogen-activated protein kinase (p38MAPK)
      and c-Jun N-terminal kinase (JNK) by immunofluorescence staining, and then were
      co-labeled with hexaribonucleotide binding protein-3 (NeuN), glial fibrillary
      acidic protein (GFAP) and anti-integrin alphaM (CD11b) antibody (OX-42) to
      explore the associations of p38MAPK and JNK with nerve cells or glial cell.
      RESULTS: Compared with sham group, the pain threshold was significantly
      decreased, and astrocyte-activated markers, GFAP and vimentin were significantly
      increased in CCI group. The mean fluorescence intensities of p38MAPK and JNK were
      increased in the right spinal dorsal horn of CCI group. The coexpression of JNK
      and GFAP was found in astrocytes of the spinal dorsal horn in CCI group.
      CONCLUSION: JNK signal transduction pathway is involved in the pain signaling
      transduction of astrocytes.

PMID- 25384403
TI  - Do we have an ideal classification system for thoracolumbar and subaxial cervical
      spine injuries: what is the expert's perspective?
AB  - STUDY DESIGN: Online questionnaire survey. OBJECTIVE: To obtain the opinion of
      experts on whether the currently available classification systems for
      thoracolumbar and subaxial cervical spine injuries meet their expectations with
      regard to the desired objectives of a good classification system and practical
      implementability. METHODS: An online survey was conducted during August-September
      2013 using a specially designed questionnaire. Members of Spine Trauma Study
      Group of International Spinal Cord Society and other spinal injury experts were
      approached, and responses were analyzed. RESULTS: Forty-two spine experts
      responded. Majority (87.50%, n=35) were involved with education and research. For
      subaxial cervical spine injuries, Allen Ferguson classification was more commonly
      used (37.50%, n=15) and thought to be practically implementable in day-to-day
      practice (30.77%). For thoracolumbar injuries, while Thoracolumbar Injury
      Classification and Severity Score (TLICS) was more commonly used (47.50%, n=19),
      the response of experts for practical implementability in day-to-day practice was
      more evenly distributed among TLICS, AO (Association for Osteosynthesis) and
      Dennis classifications (30.77, 23.08 and 25.64%, respectively). Experts felt that
      the classification systems did not serve all the desired objectives. The
      reliability for residents was especially a concern. CONCLUSION: We may still be
      far from an ideal classification system. Many experts continue to prefer or would
      consider shifting back to traditional and simpler systems. There is a need for
      developing classification systems that would be better implementable practically
      in day-to-day clinical practice, better guide treatment, be more reliable,
      incorporate other modifiers influencing treatment and be more comprehensive in
      that order of priority.

PMID- 25384404
TI  - Mild clinical manifestation and unusual recovery upon coenzyme Q10 treatment in
      the first Chinese Leigh syndrome pedigree with mutation m.10197 G>A.
AB  - The Leigh syndrome (LS), characterized by psychomotor retardation, seizures,
      nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory
      failure, is one of the most severe mitochondrial diseases. In the majority of
      cases, the disease is fatal and patients die before age 5. Mutation m.10197 G>A
      was found to relate to the severe phenotype of the Leigh syndrome. Here, we
      describe the first Chinese Leigh syndrome pedigree with this mutation. The
      proband had the characteristic brain lesions of the Leigh syndrome and presented
      a decrease in exercise tolerance and mild face paralysis. Sequencing the NADH
      dehydrogenase, subunit 3 (ND3) gene in the pedigree, revealed that the proband,
      as well as her unaffected brother, have a high mutant load in the ND3 gene,
      compared to their mother. Following one-year treatment with the coenzyme Q10, an
      obvious improvement in clinical features was observed by magnetic resonance
      imaging (MRI) in the proband. Our study and previous reports highlight the
      variability of phenotypic expression of the m.10197 G>A mutation, and suggest
      that pathogenesis of the syndrome may be affected by a number of factors. This is
      the first report on successful treatment of an LS patient carrying the mutation
      m.10197 G>A with the coenzyme Q10, indicating that Q10 may attenuate the
      mitochondrial dysfunctions caused by the m.10197 G>A mutation. 

PMID- 25384405
TI  - Essential oils and isolated compounds from Lippia alba leaves and flowers:
      antimicrobial activity and osteoclast apoptosis.
AB  - In the present study, essential oils extracted from the leaves and flowers of
      Lippia alba (Mill.) N.E.Br. (L. alba) were analyzed for their antimicrobial
      activity and their effects on osteoclasts. The periodontal pathogens,
      Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans; ATCC 43717),
      Fusobacterium nucleatum (F. nucleatum; ATCC 25586) and Porphyromonas gingivalis
      (P. gingivalis); ATCC 33277) were used in antimicrobial activity assays for
      determining the minimum inhibitory concentration (MIC) and the minimum
      bactericidal concentration (MBC), whereas Bacteroides fragilis (B. fragilis; ATCC
      25285) was used as the control microorganism. Osteoclast (OC) apoptosis was
      assessed by TUNEL assay and Fas receptor expression was detected by
      immunocytochemistry. The analysis of antimicrobial activity revealed that P.
      gingivalis had the lowest MIC values, whereas A. actinomycetemcomitans had the
      highest. L. alba essential oils were found to be toxic to human cells, although
      the compounds, carvone, limonene and citral, were non-toxic and induced apoptosis
      in the OCs. This study demonstrates that L. alba has potential biotechnological
      application in dentistry. In fact periodontal disease has a multifactorial
      etiology, and the immune response to microbial challenge leads to osteoclast
      activation and the resorption of the alveolar bone, resulting in tooth loss.

PMID- 25384406
TI  - DJ-1 knockdown inhibits growth and xenograft-induced tumor generation of human
      hepatocellular carcinoma cells.
AB  - The aim of this study was to identify potential downstream effectors of the
      oncogene DJ-1 in hepatocellular carcinoma (HCC) cell lines, and examine its role
      in the Akt signaling pathway and HCC oncogenesis. Expression of the DJ-1 protein
      was assessed by immunoblotting in several human HCC cell lines. Knockdown of DJ-1
      was achieved by transfecting DJ-1-specific short hairpin RNAs into the HepG2 HCC
      cell line. The effect of DJ-1 downregulation on phosphatase and tensin homolog
      (PTEN) and phosphorylated Akt was evaluated. In addition, cell cycle,
      proliferation, adhesion and invasion were analyzed in the DJ-1 knockdown of HepG2
      cells. The growth of HepG2-induced tumor was evaluated in a nude mouse model
      after DJ-1 silencing. Stable DJ-1 knockdown was achieved in HepG2 cells using a
      shRNA eukaryotic expression vector. Downregulation of DJ-1 increased PTEN
      expression but decreased phosphorylation of Akt in HepG2 cells. In addition, DJ-1
      knockdown resulted in the decreased proliferation, adhesion and invasion of HepG2
      cells in vitro, and inhibited the growth of HepG2-induced tumor in vivo. DJ-1
      knockdown altered the malignant behavior of HepG2 cells, potentially through the
      Akt signaling pathway, suggesting a crucial role for DJ-1 in the oncogenesis of
      HCC.

PMID- 25384408
TI  - Oscillometric casual blood pressure normative standards for Swedish children
      using ABPM to exclude casual hypertension.
AB  - BACKGROUND: Casual blood pressure (CBP) is considered a reliable proxy for
      cardiovascular health. Although the auscultatory technique is the reference
      standard method for measuring CBP, oscillometric devices are increasingly being
      used in children. We sought to establish oscillometric CBP normative standards
      for Swedish children. METHODS: Cross-sectional oscillometric CBP readings were
      obtained by the Welch Allyn Spot Vital Signs 420 monitor and measured according
      to the International Guidelines' recommendations. Participants with elevated
      oscillometric CBP levels underwent verification by the auscultatory method.
      Ambulatory blood pressure monitoring (ABPM) was used to exclude casual
      hypertension. Data on 1,470 (772 males) apparently healthy Swedish schoolchildren
      aged 6-16 years were analyzed and sex-specific reference charts normalized to age
      or height were constructed. RESULTS: Systolic and diastolic CBP values were
      significantly higher with age, height, height standard deviation score (SDS),
      body mass index (BMI), and BMI SDS. Gender differences for systolic CBP were
      present starting from age of 15 years and revealed significantly higher values in
      boys than in girls, whereas for diastolic CBP, the differences were apparent at
      the age of 12 years, with higher values in girls. Increased BMI and BMI SDS were
      positively associated with CBP levels. Positive parental history of hypertension
      turned out to be a risk factor for higher systolic and diastolic CBP across all
      ages. CONCLUSIONS: Our normative standard for CBP can be used for blood pressure
      screening and control programs in Swedish children. The use of ABPM should be
      considered to confirm the diagnosis of casual hypertension.

PMID- 25384407
TI  - Carotid artery stiffness and hemodynamic pulsatility during cognitive engagement
      in healthy adults: a pilot investigation.
AB  - BACKGROUND: The matching of vascular supply to neuronal metabolic demand during
      cognitive engagement is known as neurovascular coupling (NVC). Arterial stiffness
      is a prominent determinant of pulsatility in the systemic circulation and may
      thus indirectly impact NVC. In this pilot investigation, we explored changes in
      carotid artery stiffness and cerebrovascular hemodynamic pulsatiltiy during
      cognitive engagement in healthy adults. METHODS: Twenty-seven adults (age 39 +/-
      3 years, BMI 24 +/- 1 kg/m(2)) underwent Doppler ultrasonography of the common
      carotid artery (CCA) combined with applanation tonometry to derive (i) CCA
      elastic modulus (Ep) and beta-stiffness index; (ii) CCA flow pulsatility index
      (PI); (iii) CCA pulse pressure, (iv) CCA augmentation index (AIx). Cerebral PI
      was assessed using transcranial Doppler at the middle cerebral artery (MCA). All
      measures were made at rest and during an incongruent Stroop task. RESULTS: CCA PI
      was reduced (1.75 +/- 0.06 to 1.57 +/- 0.06, P < 0.05) while MCA PI was unchanged
      (0.75 +/- 0.02 to 0.75 +/- 0.02, P > 0.05) during Stroop. Brachial pulse pressure
      increased during Stroop (43 +/- 1 to 46 +/- 1 mm Hg, P < 0.05) while CCA pulse
      pressure was unchanged (36 +/- 1 to 35 +/- 1 mm Hg, P > 0.05). Similarly, CCA Ep
      (54.5 +/- 5.5 to 53.8 +/- 4.9 kPa, P > 0.05) and beta-stiffness index (4.4 +/-
      0.4 to 4.2 +/- 0.3 aU, P > 0.05) were unchanged. CCA AIx increased (1 +/- 4 to 13
      +/- 4%, P < 0.05). CONCLUSION: Carotid pressure pulsatility is unaltered while
      carotid flow pulsatility is reduced during cognitive engagement. Carotid artery
      stiffness does not change suggesting that factors other than the dynamic elastic
      properties of the CCA buffer cerebrovascular hemodynamic pulsatility during
      cognitive engagement.

PMID- 25384409
TI  - Azilsartan is associated with increased circulating angiotensin-(1-7) levels and
      reduced renovascular 20-HETE levels.
AB  - BACKGROUND: Activation of angiotensin (ANG) II type 1 receptors (AT1R) promotes
      vasoconstriction, inflammation, and renal dysfunction. In this study, we
      addressed the ability of azilsartan (AZL), a new AT1R antagonist, to modulate
      levels of plasma ANG-(1-7) and renal epoxyeicosatrienoic acids (EETs) and 20
      hydroxyeicosatetraenoic acid (20-HETE). METHODS: Sprague-Dawley rats were infused
      with ANG II (125 ng/min) or vehicle (VEH). AZL (3 mg/kg/day) or VEH was
      administered starting 1 day prior to ANG II or VEH infusion. On day 10, plasma
      was obtained for measurement of ANG-(1-7) and kidneys for isolation of
      microvessels for EET and 20-HETE determination and histological evaluation.
      RESULTS: Mean 24-hour blood pressure (BP) was not different between VEH and AZL
      treatment groups, whereas the BP elevation with ANG II infusion (121 +/- 5 mm Hg)
      was completely normalized with AZL cotreatment (86 +/- 3 mm Hg). The ANG II
      induced renal damage was attenuated and cardiac hypertrophy prevented with AZL
      cotreatment. Plasma ANG-(1-7) levels (pg/ml) were increased with AZL treatment
      (219 +/- 22) and AZL + ANG II infusion (264 +/- 93) compared to VEH controls
      (74.62 +/- 8). AZL treatment increased the ratio of EETs to their
      dihydroxyeicosatrienoic acid (DHET) metabolites and reduced 20-HETE levels.
      CONCLUSIONS: Treatment with AZL completely antagonized the elevation of BP
      induced by ANG II, prevented cardiac hypertrophy, attenuated renal damage, and
      increased ANG-(1-7) and EET/DHET ratio while diminishing 20-HETE levels.
      Increased ANG-(1-7) and EETs levels may emerge as novel therapeutic mechanisms
      contributing to the antihypertensive and antihypertrophic actions of AZL
      treatment and their relative role compared to AT1R blockade may depend on the
      etiology of the hypertension.

PMID- 25384410
TI  - Affective temperament in stroke patients.
AB  - OBJECTIVE: The aims of this study were to determine the dominant affective
      temperament changes in stroke survivors and whether temperament affects the
      disability. METHODS: A total of 63 stroke patients were included in this study.
      Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire
      was used to determine the dominant affective temperament (depressive,
      hyperthymic, cyclothymic, irritable or anxious). The disability level was
      measured with the Barthel index (BI). RESULTS: Depressive temperament (17.5%) and
      anxious temperament (12.7%) were the most common dominant affective temperaments.
      The frequencies of irritable, cyclothymic and hyperthymic temperaments were 4.8,
      3.2 and 0%, respectively. The mean BI score was 78.1 +/- 18.3 in patients with
      depressive temperament and 67.4 +/- 28.4 in patients without depressive
      temperament (p = 0.403). The mean BI score was 78.1 +/- 15.3 in patients with
      anxious temperament and 68.0 +/- 28.3 in patients without anxious temperament (p
      = 0.541). Multiple linear regression analysis indicated that BI score was not
      associated with affective temperament changes. CONCLUSION: The results of the
      current study suggest that depressive and anxious temperaments are the most
      common affective temperaments and that there appears to be no association between
      disability level and dominant affective temperament in stroke survivors.

PMID- 25384411
TI  - Functional impairment and previous suicide attempts in bipolar disorder.
AB  - OBJECTIVE: The aim of the present study was to assess the association between
      previous suicide attempts and functional impairment among euthymic patients with
      bipolar disorder (BD). METHODS: Seventy-one Diagnostic Statistical Manual IV (DSM
      IV) patients with BD and 61 healthy volunteers were recruited from the Bipolar
      Disorder Program at the Clinic Hospital of Barcelona. Patients with (n = 36,
      50.7%) and without (n = 35, 49.3%) previous suicide attempts were assessed using
      the Structured Clinical Interview for DSM-IV-TR (SCID-P). Previous suicide
      attempts were carefully investigated by means of patient and caregiver interview
      and by a standard structured interview from the protocol of our BD Program. The
      Functioning Assessment Short Test (FAST) was employed to assess functional
      impairment. RESULTS: Euthymic patients with previous suicide attempts showed
      functional impairment, particularly in occupational (F = 30.39; p = 0.001) and
      cognitive functioning (F = 18.43; p = 0.001). In addition, family history of
      psychiatric illness (chi2: 6.49; degrees of freedom (df) = 2;132; p = 0.010),
      family history of affective disorders (chi2 = 5.57; p = 0.017), psychotic
      symptoms (chi2 = 5.88; p = 0.014) and axis II comorbidity were associated with
      previous suicide attempts (chi2 = 5.16; p = 0.021). CONCLUSION: Bipolar patients
      with previous suicide attempts had lower overall functioning than patients who
      did not attempt suicide. Previous suicide attempts were particularly associated
      with the occupational and cognitive domains of functioning.

PMID- 25384412
TI  - Downregulation of Ccnd1 and Hes6 in rat hippocampus after chronic exposure to the
      antidepressant paroxetine.
AB  - OBJECTIVE: The mechanism of action of antidepressant drugs is not fully
      understood. Application of genomic methods enables the identification of
      biochemical pathways that are regulated by antidepressants, and this may provide
      novel clues to the molecular and cellular actions of these drugs. The present
      study examined gene expression profiles in the hippocampus of rats exposed to
      chronic antidepressant treatment. METHODS: Animals were treated for 12 days with
      the selective serotonin reuptake inhibitor paroxetine; then, hippocampal
      ribonucleic acid was recovered, and changes in gene expression were assessed by
      microarray analysis. RESULTS: A total of 160 genes that showed differential
      expression after paroxetine exposure were identified. Using functional relevance
      and observed fold change as selection criteria, the expression changes in a
      subset of these genes were confirmed by quantitative polymerase chain reaction.
      CONCLUSION: Of this subset, only two genes, cyclin D1 (Ccnd1) and hairy and
      enhancer of split 6 (Hes6), showed robust and consistent changes in expression.
      Both genes were downregulated by paroxetine, and both have been previously
      implicated in neurogenesis. Further investigation of these two genes may provide
      new insight into the mechanism of action of antidepressants.

PMID- 25384413
TI  - Partial splenectomy and use of splenic vein as an autograft for meso-Rex bypass:
      a clinical observational study.
AB  - BACKGROUND: Meso-Rex bypass (MRB) surgery is being increasingly used to treat
      chronic prehepatic portal hypertension secondary to extrahepatic portal vein
      thrombosis (EPVT) and cavernous transformation (EPVCT) in children. Rather than
      using the internal jugular vein (IJV, the traditional venous graft), we used an
      autogenous splenic vein segment graft for MRB. MATERIAL/METHODS: We examined 25
      children with extrahepatic portal hypertension and a history of recurrent upper
      gastrointestinal (GI) variceal bleeding despite previous endoscopic
      sclerotherapy. All patients had melena, splenomegaly, hypersplenism, or some
      combination thereof. Left portal vein (LPV) patency was verified in 22 patients
      using intraoperative direct portography through the umbilical vein. Partial
      splenectomy was performed to enable the harvest of the splenic vein trunk, which
      was anastomosed between the superior mesenteric vein (SMV) and the left portal
      vein (LPV). All patients were followed for 12-48 months (mean=25.6 months) and no
      patients were lost to follow-up. RESULTS: Preoperative Doppler ultrasound (US)
      imaging indicated that 18/25 patients had adequate intrahepatic portal veins for
      shunting, with no blood flow in the LPVs of 7 patients. LPV patency in 22/25
      patients was verified using intraoperative direct portography, with successful
      MRB. Shunting was converted into a portosystemic shunt in the remaining 3/25
      patients with thrombosed LPVs. A Doppler US evaluation of the vein conduit
      revealed excellent postoperative flow. The patients' mean hemoglobin, platelet,
      and white blood cell counts increased significantly, and in all cases the
      endoscopic status obviously improved after shunting. Occlusion or narrowing
      occurred in 2/22 patients after discharge. At 12 months (for 1 patient) and 24
      months (for 1 patient), the shunt was converted into a portosystemic shunt. The
      cumulative graft patency rate was 91% (20/22). CONCLUSIONS: Partial splenectomy
      and splenic vein autografting in MRB surgery can successfully resolve prehepatic
      portal hypertension and hypersplenism in children.

PMID- 25384414
TI  - A 90-year-old patient presenting with postoperative hypotension and a new murmur:
      a case report.
AB  - INTRODUCTION: Hospitalists are frequently consulted on postoperative patients
      with hypotension. Postoperative hypotension is common and can be due to variety
      of causes. Systolic anterior motion of the mitral valve leading to left
      ventricular outflow tract obstruction is a rare cause of postoperative
      hypotension and can occur without prior structural heart disease. A high index of
      suspicion can lead to early recognition of this unique condition. CASE
      PRESENTATION: A 90-year-old Caucasian woman with no known structural heart
      abnormality was admitted to the intensive care unit with hypotension after a left
      hip arthroplasty revision. A transthoracic echocardiogram revealed systolic
      anterior motion of the mitral valve and dynamic left ventricular outflow tract
      obstruction as the likely cause of her hypotension. Our patient was treated with
      fluid resuscitation and phenylephrine with improvement in blood pressure. A
      repeat echocardiogram on postoperative day 5 showed resolution of the left
      ventricular outflow tract obstruction. Intraoperative vasodilatation and volume
      loss that caused underfilling of the left ventricle likely led to dynamic outflow
      tract obstruction in our patient. CONCLUSIONS: Hospitalists should be aware of
      systolic anterior motion of the mitral valve as a rare peri-operative
      complication in patients with or without underlying cardiac pathology as it is
      treated differently than other causes of peri-operative hypotension. Clinical
      suspicion, early recognition, and prompt treatment can improve clinical outcomes
      in these patients.

PMID- 25384415
TI  - Social factors in childhood and risk of depressive symptoms among adolescents--a
      longitudinal study in Stockholm, Sweden.
AB  - BACKGROUND: In Sweden, self-reported depressive symptoms have increased among
      young people of both genders, but little is known about social differences in the
      risk of depressive symptoms among adolescents in welfare states, where such
      differences can be less pronounced. Therefore, the aim was to investigate whether
      multiple measures of low social status in childhood affect depressive symptoms in
      adolescence. A secondary aim was to explore potential gender effect modification.
      METHODS: Participants were recruited in 1998 for a longitudinal study named
      BROMS. The study population at baseline consisted of 3020 children, 11-12 years
      old, from 118 schools in Stockholm County, followed up through adolescence. This
      study is based on 1880 adolescents answering the follow-up survey in 2004, at age
      17-18 (62% of the initial cohort). Parental education, occupation, country of
      birth, employment status and living arrangements were reported at baseline, by
      parents and adolescents. Depressive symptoms were self-reported by the
      adolescents in 2004, using a 12-item inventory. The associations between
      childhood social status and depressive symptoms in adolescence are presented as
      Odds Ratios (OR), estimated through logistic regression. Gender interaction with
      social factors was estimated through Synergy Index (SI). RESULTS: Increased risk
      of depressive symptoms was found among adolescents whose parents had low
      education (OR 1.8, CI = 1.1-3.1), were unskilled workers (OR 2.1, CI = 1.2-3.7),
      intermediate non-manual workers (OR 1.8, CI = 1.0-3.0), or self-employed (OR 2.2,
      CI = 1.2-3.7), compared to parents with high education and high non-manual work.
      In addition, adolescents living exclusively with one adult had an increased risk
      compared to those living with two (OR 2.8, CI = 1.1-7.5), while having foreign
      born parents was not associated with depressive symptoms. An interaction effect
      was seen between gender and social factors, with an increased risk for girls of
      low-educated parents (SI = 3.4, CI = 1.3-8.9) or living exclusively with one
      adult (SI = 4.9, CI = 1.4-6.8). CONCLUSIONS: The low social position in childhood
      may increase the risk of depressive symptoms among adolescents even in countries
      with small social differences and a highly developed welfare system, such as
      Sweden. Girls with low educated parents or living exclusively with one adult may
      be particularly vulnerable. This knowledge is of importance when planning
      preventive interventions or treatment.

PMID- 25384417
TI  - Interplay between the Kondo effect and the Ruderman-Kittel-Kasuya-Yosida
      interaction.
AB  - The interplay between the Ruderman-Kittel-Kasuya-Yosida interaction and the Kondo
      effect is expected to provide the driving force for the emergence of many
      phenomena in strongly correlated electron materials. Two magnetic impurities in a
      metal are the smallest possible system containing all these ingredients and
      define a bottom-up approach towards a long-term understanding of
      concentrated/dense systems. Here we report on the experimental and theoretical
      investigation of iron dimers buried below a Cu(100) surface by means of low
      temperature scanning tunnelling spectroscopy combined with density functional
      theory and numerical renormalization group calculations. The Kondo effect, in
      particular the width of the Abrikosov-Suhl resonance, is strongly altered or even
      suppressed due to magnetic coupling between the impurities. It oscillates as a
      function of dimer separation revealing that it is related to indirect exchange
      interactions mediated by the conduction electrons. 

PMID- 25384416
TI  - Neuroprotection by acetyl-11-keto-beta-Boswellic acid, in ischemic brain injury
      involves the Nrf2/HO-1 defense pathway.
AB  - Stroke is a complex disease involved oxidative stress-related pathways in its
      pathogenesis. The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme
      oxygenase-1 (HO-1) pathway has been considered a potential target for
      neuroprotection in stroke. Acetyl-11-Keto-beta-Boswellic Acid (AKBA) is an active
      triterpenoid compound from the extract of Boswellia serrate. The present study
      was to determine whether AKBA, a novel Nrf2 activator, can protect against
      cerebral ischemic injury. The stroke model was produced in Sprague-Dawley rats
      via middle cerebral artery occlusion. To model ischemia-like conditions in vitro,
      primary cultured cortical neurons were exposed to transient oxygen and glucose
      deprivation (OGD). Treatment of AKBA significantly reduced infarct volumes and
      apoptotic cells, and also increased neurologic scores by elevating the Nrf2 and
      HO-1 expression in brain tissues in middle cerebral artery occlusion (MCAO) rats
      at 48 hours post reperfusion. In primary cultured neurons, AKBA increased the
      Nrf2 and HO-1 expression, which provided protection against OGD-induced oxidative
      insult. Additionally, AKBA treatment increased Nrf2 binding activity to
      antioxidant-response elements (ARE). The protective effect of AKBA was attenuated
      by knockdown of Nrf2 or HO-1. In conclusion, these findings provide evidence that
      AKBA protects neurons against ischemic injury, and this neuroprotective effect
      involves the Nrf2/HO-1 pathway.

PMID- 25384418
TI  - Mapping QTL for the traits associated with heat tolerance in wheat (Triticum
      aestivum L.).
AB  - BACKGROUND: High temperature (heat) stress during grain filling is a major
      problem in most of the wheat growing areas. Developing heat tolerant cultivars
      has become a principal breeding goal in the Southern and Central Great Plain
      areas of the USA. Traits associated with high temperature tolerance can be used
      to develop heat tolerant cultivars in wheat. The present study was conducted to
      identify chromosomal regions associated with thylakoid membrane damage (TMD),
      plasmamembrane damage (PMD), and SPAD chlorophyll content (SCC), which are
      indicative of high temperature tolerance. RESULTS: In this study we have reported
      one of the first linkage maps in wheat using genotype by sequencing SNP (GBS-SNP)
      markers to extreme response to post anthesis heat stress conditions. The linkage
      map was comprised of 972 molecular markers (538 Bin, 258 AFLPs, 175 SSRs, and an
      EST). The genotypes of the RIL population showed strong variation for TMD, SCC
      and PMD in both generations (F10 and F9). Composite interval mapping identified
      five QTL regions significantly associated with response to heat stress.
      Associations were identified for PMD on chromosomes 7A, 2B and 1D, SCC on 6A, 7A,
      1B and 1D and TMD on 6A, 7A and 1D. The variability (R(2)) explained by these QTL
      ranged from 11.9 to 30.6% for TMD, 11.4 to 30.8% for SCC, and 10.5 to 33.5% for
      PMD. Molecular markers Xbarc113 and AFLP AGCTCG-347 on chromosome 6A, Xbarc121
      and Xbarc49 on 7A, gwm18 and Bin1130 on 1B, Bin178 and Bin81 on 2B and Bin747 and
      Bin1546 on 1D were associated with these QTL. CONCLUSION: The identified QTL can
      be used for marker assisted selection in breeding wheat for improved heat
      tolerance in Ventnor or Karl 92 genetic background.

PMID- 25384419
TI  - Ameliorating Patient Stigma Amongst Staff Working With Personality Disorder:
      Randomized Controlled Trial of Self-Management Versus Skills Training.
AB  - BACKGROUND: Patients diagnosed with a personality disorder (PD) are often
      stigmatized by the healthcare staff who treat them. AIMS: This study aimed to
      compare the impact on front-line staff of a self-management Acceptance and
      Commitment Therapy-based training intervention (ACTr) with a knowledge- and
      skills-based Dialectical Behaviour Training intervention (DBTr). METHOD: A
      service-based randomized controlled trial was conducted comparing the effects of
      2-day ACTr (N = 53) and DBTr (N = 47) staff workshops over 6 months. Primary
      outcome measures were staff attitudes towards patients and staff-patient
      relationships. RESULTS: For both interventions, staff attitudes, therapeutic
      relationship, and social distancing all improved pre- to postintervention, and
      these changes were maintained at 6-month follow-up. CONCLUSIONS: Although
      offering different resources to staff, both ACTr and DBTr were associated with an
      improved disposition towards PD patients. Future research could evaluate a
      combined approach, both for staff working with PD patients and those working with
      other stigmatized groups.

PMID- 25384420
TI  - Designer self-assembling hydrogel scaffolds can impact skin cell proliferation
      and migration.
AB  - There is a need to develop economical, efficient and widely available therapeutic
      approaches to enhance the rate of skin wound healing. The optimal outcome of
      wound healing is restoration to the pre-wound quality of health. In this study we
      investigate the cellular response to biological stimuli using functionalized
      nanofibers from the self-assembling peptide, RADA16. We demonstrate that adding
      different functional motifs to the RADA16 base peptide can influence the rate of
      proliferation and migration of keratinocytes and dermal fibroblasts. Relative to
      unmodified RADA16; the Collagen I motif significantly promotes cell migration,
      and reduces proliferation. 

PMID- 25384421
TI  - Targeting Hippo pathway by specific interruption of YAP-TEAD interaction using
      cyclic YAP-like peptides.
AB  - Hippo signaling pathway is emerging as a novel target for anticancer therapy
      because it plays key roles in organ size control and tumorigenesis. As the
      downstream effectors, Yes-associated protein (YAP)-transcriptional enhancer
      activation domain family member (TEAD) association is essential for YAP-driven
      oncogenic activity, while TEAD is largely dispensable for normal tissue growth.
      We present the design of YAP-like peptides (17mer) to occupy the interface 3 on
      TEAD. Introducing cysteines at YAP sites 87 and 96 can induce disulfide
      formation, as confirmed by crystallography. The engineered peptide significantly
      improves the potency in disrupting YAP-TEAD interaction in vitro. To confirm that
      blocking YAP-TEAD complex formation by directly targeting on TEAD is a valid
      approach, we report a significant reduction in tumor growth rate in a
      hepatocellular carcinoma xenograft model after introducing the dominant-negative
      mutation (Y406H) of TEAD1 to abolish YAP-TEAD interaction. Our results suggest
      that targeting TEAD is a promising strategy against YAP-induced oncogenesis.

PMID- 25384422
TI  - Activation of the Wnt/beta-catenin pathway represses the transcription of the
      beta-amyloid precursor protein cleaving enzyme (BACE1) via binding of T-cell
      factor-4 to BACE1 promoter.
AB  - Alterations in the Wnt signaling pathway have been implicated in Alzheimer's
      disease; however, its role in the processing of the amyloid precursor protein
      remains unknown. In this study, activation of the Wnt pathway by overexpression
      of the agonist Wnt3a or beta-catenin or by inhibition of glycogen kinase synthase
      3 in N2a cells resulted in a reduction in Abeta levels and in the activity and
      expression of BACE1 (beta-APP cleaving enzyme). Conversely, inhibition of the
      pathway by transfection of the antagonists secreted frizzled receptor protein-1
      or dickkopf-1 produced the opposite effects. Chromatin immunoprecipitation
      analysis demonstrated that beta-catenin binds specifically to regions within the
      promoter of BACE1 containing putative T-cell factor/lymphoid enhancer binding
      factor-1 (TCF/LEF) motifs, consistent with canonical Wnt target regulation.
      Furthermore, cells transfected with beta-catenin mutants incapable of binding to
      TCF/LEF increased BACE1 gene promoter activity. Interestingly, TCF4 knockdown
      reversed the effects of Wnt3a activation on BACE1 transcription. We found that
      TCF4 binds to the same region on BACE1 promoter following Wnt3a stimulation,
      indicating that TCF4 functions as a transcriptional repressor of BACE1 gene. In
      conclusion, Wnt/beta-catenin stimulation may repress BACE1 transcription via
      binding of TCF4 to BACE1 gene, and therefore, activation of the Wnt pathway may
      hold the key to new treatments of Alzheimer disease.-Parr, C., Mirzaei, N.,
      Christian, M., and Sastre, M. Activation of the Wnt/beta-catenin pathway
      represses the transcription of the beta-amyloid precursor protein cleaving enzyme
      (BACE1) via binding of T-cell factor-4 to BACE1 promoter. 

PMID- 25384425
TI  - Confined surface plasmon sensors based on strongly coupled disk-in-volcano
      arrays.
AB  - Disk-in-volcano arrays are reported to greatly enhance the sensing performance
      due to strong coupling in the nanogaps between the nanovolcanos and nanodisks.
      The designed structure, which is composed of a nanovolcano array film and a disk
      in each cavity, is fabricated by a simple and efficient colloidal lithography
      method. By tuning structural parameters, the disk-in-volcano arrays show greatly
      enhanced resonances in the nanogaps formed by the disks and the inner wall of the
      volcanos. Therefore they respond to the surrounding environment with a
      sensitivity as high as 977 nm per RIU and with excellent linear dependence on the
      refraction index. Moreover, through mastering the fabrication process, biological
      sensing can be easily confined to the cavities of the nanovolcanos. The local
      responsivity has the advantages of maximum surface plasmon energy density in the
      nanogaps, reducing the sensing background and saving expensive reagents. The disk
      in-volcano arrays also possess great potential in applications of optical and
      electrical trapping and single-molecule analysis, because they enable
      establishment of electric fields across the gaps. 

PMID- 25384423
TI  - Folic acid deficiency induces premature hearing loss through mechanisms involving
      cochlear oxidative stress and impairment of homocysteine metabolism.
AB  - Nutritional imbalance is emerging as a causative factor of hearing loss.
      Epidemiologic studies have linked hearing loss to elevated plasma total
      homocysteine (tHcy) and folate deficiency, and have shown that folate
      supplementation lowers tHcy levels potentially ameliorating age-related hearing
      loss. The purpose of this study was to address the impact of folate deficiency on
      hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old
      C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2
      groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8
      wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold
      increase in tHcy levels. FD mice exhibited severe hearing loss measured by
      auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT
      quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing
      homocysteine (Hcy) production and recycling, together with a 30% increase in
      protein homocysteinylation. Redox stress was demonstrated by decreased expression
      of catalase, glutathione peroxidase 4, and glutathione synthetase genes,
      increased levels of manganese superoxide dismutase, and NADPH oxidase-complex
      adaptor cytochrome b-245, alpha-polypeptide (p22phox) proteins, and elevated
      concentrations of glutathione species. Altogether, our findings demonstrate, for
      the first time, that the relationship between hyperhomocysteinemia induced by
      folate deficiency and premature hearing loss involves impairment of cochlear Hcy
      metabolism and associated oxidative stress.

PMID- 25384424
TI  - N-Acylethanolamine-hydrolyzing acid amidase inhibition increases colon N
      palmitoylethanolamine levels and counteracts murine colitis.
AB  - N-Palmitoylethanolamine or palmitoylethanolamide (PEA) is an anti-inflammatory
      compound that was recently shown to exert peroxisome proliferator-activated
      receptor-alpha-dependent beneficial effects on colon inflammation. The actions of
      PEA are terminated following hydrolysis by 2 enzymes: fatty acid amide hydrolase
      (FAAH), and the less-studied N-acylethanolamine-hydrolyzing acid amidase (NAAA).
      This study aims to investigate the effects of inhibiting the enzymes responsible
      for PEA hydrolysis in colon inflammation in order to propose a potential
      therapeutic target for inflammatory bowel diseases (IBDs). Two murine models of
      IBD were used to assess the effects of NAAA inhibition, FAAH inhibition, and PEA
      on macroscopic signs of colon inflammation, macrophage/neutrophil infiltration,
      and the expression of proinflammatory mediators in the colon, as well as on the
      colitis-related systemic inflammation. NAAA inhibition increases PEA levels in
      the colon and reduces colon inflammation and systemic inflammation, similarly to
      PEA. FAAH inhibition, however, does not increase PEA levels in the colon and does
      not affect the macroscopic signs of colon inflammation or immune cell
      infiltration. This is the first report of an anti-inflammatory effect of a
      systemically administered NAAA inhibitor. Because NAAA is the enzyme responsible
      for the control of PEA levels in the colon, we put forth this enzyme as a
      potential therapeutic target in chronic inflammation in general and IBD in
      particular.

PMID- 25384428
TI  - Can combining femoral and acetabular morphology parameters improve the
      characterization of femoroacetabular impingement?
AB  - BACKGROUND: Femoroacetabular impingement (FAI) presupposes a dynamic interaction
      of the proximal femur and acetabulum producing clinical symptoms and
      chondrolabral damage. Currently, FAI classification is based on alpha angle and
      center-edge angle measurements in a single plane. However, acetabular and femoral
      version and neck-shaft angle also influence FAI. Furthermore, each of these
      parameters has a reciprocal interaction with the others; for example, a shallow
      acetabulum delays impingement of the femoral head with the acetabular rim.
      QUESTIONS/PURPOSES: We introduce the new parameter "omega zone," which combines
      five parameters into one: the alpha and center-edge angles, acetabular and
      femoral version, and neck-shaft angle. We sought to determine whether the omega
      zone could differentiate patients with FAI from (1) normal control subjects
      (alpha < 55 degrees ), but also from (2) control subjects with elevated alpha
      angles (>= 55 degrees ). METHODS: We evaluated CT data of 20 hips of male
      patients with symptomatic cam-type FAI and of 35 male hips extracted from 110
      anonymized CT scans for vascular diagnosis. We excluded hips with osteoarthritis,
      developmental dysplasia, or coxa profunda (center-edge angle 20 degrees -45
      degrees  on AP pelvic view or corresponding coronal CT views). With dedicated
      software, femoral and pelvic orientation was standardized; we tested the omega
      zone in four hip positions in three distinct groups: patients with cam-type FAI
      (alpha > 60 degrees ) and control subjects with normal (< 55 degrees ) and high
      alpha angles (>= 55 degrees ). RESULTS: The omega zone was smaller in patients
      with cam-type FAI than normal control subjects (alpha angle < 55 degrees ) at 60
      degrees  and 90 degrees  of flexion (mean, 12%; 95% confidence interval [CI], 7
      17; p = 0.008; Cohen's d = 9%; 95% CI, 4-13; p = 0.003). Furthermore, the omega
      zone was smaller in all positions in patients with cam-type FAI than control
      subjects with high alpha angles (0 degrees  p = 0.017, 30 degrees  p = 0.004, 60
      degrees  p = 0.004, 90 degrees  p = 0.007). In contrast, the omega zone did not
      differ between control subjects with normal or high alpha angles. In all hips,
      the omega zone decreased with flexion, corresponding to a decrease in remaining
      impingement-free motion with flexion. CONCLUSIONS: The omega zone visualizes and
      quantifies the interaction of the proximal femur and acetabulum. The omega zone
      differed between patients with cam-type FAI and control subjects with high alpha
      angles (>= 55 degrees ), who could not be distinguished based on alpha angle
      alone. For hip-preserving surgery, it can help surgeons decide whether to address
      the femur, the acetabulum, or both.

PMID- 25384429
TI  - What are the radiographic reference values for acetabular under- and
      overcoverage?
AB  - BACKGROUND: Both acetabular undercoverage (hip dysplasia) and overcoverage
      (pincer-type femoroacetabular impingement) can result in hip osteoarthritis. In
      contrast to undercoverage, there is a lack of information on radiographic
      reference values for excessive acetabular coverage. QUESTIONS/PURPOSES: (1) How
      do common radiographic hip parameters differ in hips with a deficient or an
      excessive acetabulum in relation to a control group; and (2) what are the
      reference values determined from these data for acetabular under- and
      overcoverage? METHODS: We retrospectively compared 11 radiographic parameters
      describing the radiographic acetabular anatomy among hip dysplasia (26 hips
      undergoing periacetabular osteotomy), control hips (21 hips, requiring no rim
      trimming during surgical hip dislocation), hips with overcoverage (14 hips,
      requiring rim trimming during surgical hip dislocation), and hips with severe
      overcoverage (25 hips, defined as having acetabular protrusio). The hips were
      selected from a patient cohort of a total of 593 hips. Radiographic parameters
      were assessed with computerized methods on anteroposterior pelvic radiographs and
      corrected for neutral pelvic orientation with the help of a true lateral
      radiograph. RESULTS: All parameters except the crossover sign differed among the
      four study groups. From dysplasia through control and overcoverage, the lateral
      center-edge angle, acetabular arc, and anteroposterior/craniocaudal coverage
      increased. In contrast, the medial center-edge angle, extrusion/acetabular index,
      Sharp angle, and prevalence of the posterior wall sign decreased. The following
      reference values were found: lateral center-edge angle 23 degrees  to 33 degrees
      , medial center-edge angle 35 degrees  to 44 degrees , acetabular arc 61 degrees 
      to 65 degrees , extrusion index 17% to 27%, acetabular index 3 degrees  to 13
      degrees , Sharp angle 38 degrees  to 42 degrees , negative crossover sign,
      positive posterior wall sign, anterior femoral head coverage 15% to 26%,
      posterior femoral head coverage 36% to 47%, and craniocaudal coverage 70% to 83%.
      CONCLUSIONS: These acetabular reference values define excessive and deficient
      coverage. They may be used for radiographic evaluation of symptomatic hips, may
      offer possible predictors for surgical outcomes, and serve to guide clinical
      decision-making.

PMID- 25384430
TI  - Head reduction osteotomy with additional containment surgery improves sphericity
      and containment and reduces pain in Legg-Calve-Perthes disease.
AB  - BACKGROUND: Severe femoral head deformities in the frontal plane such as hips
      with Legg-Calve-Perthes disease (LCPD) are not contained by the acetabulum and
      result in hinged abduction and impingement. These rare deformities cannot be
      addressed by resection, which would endanger head vascularity. Femoral head
      reduction osteotomy allows for reshaping of the femoral head with the goal of
      improving head sphericity, containment, and hip function. QUESTIONS/PURPOSES:
      Among hips with severe asphericity of the femoral head, does femoral head
      reduction osteotomy result in (1) improved head sphericity and containment; (2)
      pain relief and improved hip function; and (3) subsequent reoperations or
      complications? METHODS: Over a 10-year period, we performed femoral head
      reduction osteotomies in 11 patients (11 hips) with severe head asphericities
      resulting from LCPD (10 hips) or disturbance of epiphyseal perfusion after
      conservative treatment of developmental dysplasia (one hip). Five of 11 hips had
      concomitant acetabular containment surgery including two triple osteotomies, two
      periacetabular osteotomies (PAOs), and one Colonna procedure. Patients were
      reviewed at a mean of 5 years (range, 1-10 years), and none was lost to followup.
      Mean patient age at the time of head reduction osteotomy was 13 years (range, 7
      23 years). We obtained the sphericity index (defined as the ratio of the minor to
      the major axis of the ellipse drawn to best fit the femoral head articular
      surface on conventional anteroposterior pelvic radiographs) to assess head
      sphericity. Containment was assessed evaluating the proportion of patients with
      an intact Shenton's line, the extrusion index, and the lateral center-edge (LCE)
      angle. Merle d'Aubigne-Postel score and range of motion (flexion,
      internal/external rotation in 90 degrees  of flexion) were assessed to measure
      pain and function. Complications and reoperations were identified by chart
      review. RESULTS: At latest followup, femoral head sphericity (72%; range, 64%-81%
      preoperatively versus 85%; range, 73%-96% postoperatively; p = 0.004), extrusion
      index (47%; range, 25%-60% versus 20%; range, 3%-58%; p = 0.006), and LCE angle
      (1 degrees ; range, -10 degrees  to 16 degrees  versus 26 degrees ; range, 4
      degrees -40 degrees ; p = 0.0064) were improved compared with preoperatively.
      With the limited number of hips available, the proportion of an intact Shenton's
      line (64% versus 100%; p = 0.087) and the overall Merle d'Aubigne-Postel score
      (14.5; range, 12-16 versus 15.7; range, 12-18; p = 0.072) remained unchanged at
      latest followup. The Merle d'Aubigne-Postel pain subscore improved (3.5; range, 1
      5 versus 5.0; range, 3-6; p = 0.026). Range of motion was not observed to have
      improved with the numbers available (p ranging from 0.513 to 0.778). In addition
      to hardware removal in two hips, subsequent surgery was performed in five of 11
      hips to improve containment after a mean interval of 2.3 years (range, 0.2-7.5
      years). Of those, two hips had triple osteotomy, one hip a combined triple and
      valgus intertrochanteric osteotomy, one hip an intertrochanteric varus osteotomy,
      and one hip a PAO with a separate valgus intertrochanteric osteotomy. No
      avascular necrosis of the femoral head occurred. CONCLUSIONS: Femoral head
      reduction osteotomy can improve femoral head sphericity. Improved head
      containment in these hips with an often dysplastic acetabulum requires additional
      acetabular containment surgery, ideally performed concomitantly. This can result
      in reduced pain and avascular necrosis seems to be rare. With the number of
      patients available, function did not improve. Therefore, future studies should
      use more precise instruments to evaluate clinical outcome and include longer
      followup to confirm joint preservation.

PMID- 25384431
TI  - Intact parathyroid hormone and whole parathyroid hormone assay results disagree
      in hemodialysis patients under cinacalcet hydrochloride therapy.
AB  - BACKGROUND: The parathyroid gland secretes 1-84 and 7-84 parathyroid hormone
      (PTH) fragments, and its regulation is dependent on stimulation of the
      extracellular calcium-sensing receptor. While the intact PTH system detects both
      PTH fragments, the whole PTH system detects the 1-84PTH but not the 7-84PTH.
      Cinacalcet hydrochloride (CH) binds to calcium-sensing receptor as a
      calcimimetic. Here we investigated the role of CH treatment in the assessment of
      parathyroid gland function. METHODS: Stable adult dialysis patients for whom CH
      therapy was planned were included. Patients for whom CH therapy was not planned
      were simultaneously included as the control group. RESULTS: The CH group (n = 44)
      showed significantly higher circulating levels of Ca, intact PTH, and whole PTH,
      before the CH treatment than the control group (n = 112). The Ca, intact PTH, and
      whole PTH levels decreased along with the CH therapy, and the Ca levels became
      comparable in the 8th week of treatment and thereafter. The CH group in the 8th
      week and thereafter showed significantly lower whole/intact PTH ratios than the
      control group, while the whole/intact PTH ratio was not significantly different
      between before and during the CH therapy. A multiple regression analysis revealed
      that the whole/intact PTH ratio was almost constant, but both the serum Ca level
      and a CH therapy could potentially modify the fixed number. When the whole PTH
      levels were estimated by intact PTH levels using the relationship between them in
      the control group, the levels were clearly overestimated in the CH group.
      CONCLUSIONS: Although the direct effect of CH on the whole/intact PTH ratio is
      masked by its hypocalcemic action, we could successfully demonstrate that the
      ratio in CH users is lower than that in the non-users with comparable levels of
      serum Ca. Evaluating parathyroid function with intact PTH according to the
      clinical practice guidelines in patients being treated with CH may lead to
      significant overestimation and subsequent overtreatment.

PMID- 25384432
TI  - Osteoporosis after renal transplantation.
AB  - Bone loss and fracture are serious sequelae of kidney transplantation, associated
      with morbidity, mortality and high economic costs. The pathogenesis of post
      transplantation bone loss is multifactorial and complex. Pre-existing bone
      mineral disease is responsible for a significant part, but it is aggravated by
      risk factors emerging after renal transplantation with immunosuppressive agents
      being one of the key contributors. The decrease in bone mass is particularly
      prominent during the first 6-12 months after transplantation, continuing at a
      lower rate thereafter. Bone mineral density measurements do not predict bone
      histology and bone biopsy findings reveal heterogeneous lesions, which vary
      according to time after transplantation. Currently, vitamin D and bisphosphonates
      are the most extensively tested therapeutic agents against this accelerated bone
      loss in renal transplant recipients. Both of these agents have proven effective,
      but there is no evidence that they decrease fracture risk. More studies are
      needed to examine the complex pathophysiologic mechanisms implicated in this
      population, as well as the effects of different therapeutic interventions on bone
      disorders after kidney transplantation.

PMID- 25384433
TI  - Prognostic role of HER2 expression in bladder cancer: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: The prognostic role of human epidermal growth factor receptor 2 (HER2)
      in bladder cancer (BCa) remains controversial. Thus, we conducted a meta-analysis
      to assess the prognostic significance of HER2 for patients with BCa. MATERIALS
      AND METHODS: Systematically computerised searching in PubMed, Scopus database,
      Embase and Cochrane Library Database was conducted. Published studies comparing
      the prognosis in patients with BCa stratified by HER2 status were included, and
      relationships between HER2 positivity and gender, stage, grade, lymph node
      metastasis and survival were analysed. RESULTS: Nine studies with 2,242 eligible
      patients were identified. HER2 expression was significantly correlated with poor
      disease-specific survival [pooled hazard ratio (HR) 2.00; 95% confidence interval
      (CI) 1.22-3.29; P=0.006] and disease-free survival (pooled HR 1.68; 95% CI 1.33
      2.14; P<0.0001) of patients with BCa. The positive rates of HER2 ranged from 27.8
      to 85.2% with a pooled positive rate of 41.2% (1,006/2,442). HER2 expression was
      significantly associated with tumour grade [high grade vs. low grade: odds ratio
      (OR) 4.08; 95% CI 1.29-12.93] and lymph node metastasis (positive vs. negative:
      OR 1.71; 95% CI 1.07-2.75). CONCLUSIONS: This meta-analysis indicated that HER2
      expression is associated with poor prognosis. Thus, HER2 could serve as a useful
      biomarker for clinical prediction.

PMID- 25384434
TI  - Penile cancer: impact of age at diagnosis on morphology and prognosis.
AB  - PURPOSE: In order to describe epidemiological and pathological features of penile
      cancer in a high-risk area of Brazil. METHODS: We reviewed the experience (378
      patients from 1997 to 2007) of Hospital Aristides Maltez from Salvador, Bahia-the
      main institution in the state which provides oncologic treatment for penile
      cancer in the public health system. RESULTS: The present series showed a high
      rate (17 %) of patients less than 40 years at the time of diagnosis. Cancer
      specific death rate in this age group was 19 % (in contrast to 11 and 13 % in the
      41-60 and >60 age groups). Squamous cell carcinomas in younger patients were also
      more likely to exhibit infiltrative growth pattern, perineural invasion, and
      recurrence. CONCLUSION: Regardless of tumor subtypes, penile carcinoma in
      Northeastern Brazil had more aggressive features and behavior when presented at
      younger age. This observation should be confirmed in other large series from
      endemic areas of penile cancer.

PMID- 25384435
TI  - Destination memory and familiarity: better memory for conversations with Elvis
      Presley than with unknown people.
AB  - BACKGROUND AND AIMS: Familiarity is assumed to exert a beneficial effect on
      memory in older adults. Our paper investigated this issue specifically for
      destination memory, that is, memory of the destination of previously relayed
      information. METHODS: Young and older adults were told familiar (Experiment 1)
      and unfamiliar (Experiment 2) proverbs associated with pictures depicting faces
      of celebrities (e.g., Elvis Presley) or unknown people, with a specific proverb
      assigned to each face. In a later recognition task, participants were presented
      with the previously exposed proverb-face pairs and for each pair had to decide
      whether they had previously relayed the given proverb to the given face. RESULTS:
      In general, destination performance was found to be higher for familiar than for
      unfamiliar faces. However while there was no difference between the two groups
      when the proverbs being relayed were unfamiliar, the advantage of face
      familiarity on destination memory was present only for older adults when the
      proverbs being relayed were familiar. DISCUSSION AND CONCLUSIONS: Our results
      show that destination memory in older adults is sensitive to familiarity of both
      destination and output information.

PMID- 25384436
TI  - Revising the link between proton-pump inhibitors and risk of acute myocardial
      infarction-a case-crossover analysis.
AB  - PURPOSE: The purpose of this study is to investigate if the prescription of
      proton-pump inhibitors (PPIs) was associated with a sudden risk of acute
      myocardial infarction (AMI) while controlling for time-invariant confounding by
      using a case-crossover design. An association might indicate that physicians take
      prodromal symptoms of myocardial ischaemia for dyspepsia. METHODS: We applied a
      case-crossover design to investigate all AMI patients admitted to the hospital in
      the Skane region, Sweden, between Oct 14, 2005 and Dec 31, 2006 and their PPI
      prescriptions and dispensations 3 months prior to the AMI onset. We retrieved the
      information about prescribed medication from the Swedish Drug Register containing
      individual information on all dispensed drugs prescribed in the outpatient care
      and dispensed in any of the Swedish pharmacies. Additionally, we stratified the
      analyses by history of AMI. RESULTS: We identified 3490 AMI cases aged 40 to 90;
      61 % were men. The odds ratio for AMI onset in those with a prescription of PPIs
      during a hazard period of 3 days compared to control periods was 1.36 (95 %
      confidence interval (CI) 0.82-2.25) in the whole study cohort and 1.66 (95 % CI
      1.00-2.76) in those without history of AMI. The corresponding odds ratio (OR)
      based on the dispensation date (suggesting use of the drug) was 1.26 (95 % CI
      0.92-1.72) and 1.29 (95 % CI 0.92-1.83), respectively. CONCLUSIONS: In our
      opinion, the previously reported increase in risk of adverse cardiac events in
      patients using PPIs may reflect the fact that an AMI may be misinterpreted as
      dyspepsia.

PMID- 25384437
TI  - A Molluscum contagiosum fusion protein inhibits CCL1-induced chemotaxis of cells
      expressing CCR8 and penetrates human neonatal foreskins: clinical applications
      proposed.
AB  - Inflammation in atopic dermatitis is mediated in part by the chemokine CCL1 and
      its receptor, CCR8. Recombinant Molluscum contagiosum viral protein (rMC148p), a
      cc-chemokine homolog, inhibits CCL1-induced chemotaxis of cells expressing CCR8.
      rMC148p was prepared using the baculovirus/Sf9 insect cell expression system. The
      recombinant MC148 fusion protein (rMC148fp), rMC148-TAT-6xHis, was similarly
      prepared by adding base sequences onto the PCR primers to fuse TAT and 6xHis to
      rMC148p at the carboxyl terminus. rMC148fp retains the capacity of rMC148p to
      inhibit CCL1-induced chemotaxis. Furthermore, unlike rMC148p, topically applied
      rMC148fp penetrates stratum corneum of human neonatal foreskins and concentrates
      along the basal and lower spinous cell layers of the epidermis. rMC148fp may be a
      safe and effective agent in the treatment of atopic dermatitis and other CCR8
      mediated disorders.

PMID- 25384438
TI  - Human endogenous retrovirus expression is inversely related with the up
      regulation of interferon-inducible genes in the skin of patients with lichen
      planus.
AB  - Lichen planus (LP) is a common inflammatory skin disease of unknown etiology.
      Reports of a common transactivation of quiescent human endogenous retroviruses
      (HERVs) support the connection of viruses to the disease. HERVs are ancient
      retroviral sequences in the human genome and their transcription is often
      deregulated in cancer and autoimmune diseases. We explored the transcriptional
      activity of HERV sequences as well as the antiviral restriction factor and
      interferon-inducible genes in the skin from LP patients and healthy control (HC)
      donors. The study included 13 skin biopsies from patients with LP and 12
      controls. Real-time PCR assay identified significant decrease in the HERV-K gag
      and env mRNA expression levels in LP subjects, when compared to control group.
      The expressions of HERV-K18 and HERV-W env were also inhibited in the skin of LP
      patients. We observed a strong correlation between HERV-K gag with other HERV
      sequences, regardless the down-modulation of transcripts levels in LP group. In
      contrast, a significant up-regulation of the cytidine deaminase APOBEC 3G
      (apolipoprotein B mRNA-editing), and the GTPase MxA (Myxovirus resistance A) mRNA
      expression level was identified in the LP skin specimens. Other transcript
      expressions, such as the master regulator of type I interferon-dependent immune
      responses, STING (stimulator of interferon genes) and IRF-7 (interferon
      regulatory factor 7), IFN-beta and the inflammassome NALP3, had increased levels
      in LP, when compared to HC group. Our study suggests that interferon-inducible
      factors, in addition to their role in innate immunity against exogenous
      pathogens, contribute to the immune control of HERVs. Evaluation of the balance
      between HERV and interferon-inducible factor expression could possibly contribute
      to surveillance of inflammatory/malignant status of skin diseases.

PMID- 25384440
TI  - Identification of soluble and membrane antigenic markers of acquired
      toxoplasmosis by immunoblot.
AB  - The overall performance of quantitative assays in the detection of anti
      Toxoplasma IgG is satisfactory, but discrepancies between assays are not uncommon
      especially when IgG concentrations are close to the limit of detection of the
      tests. The purpose of our study was to identify soluble and membrane antigens
      extracted from Toxoplasma gondii tachyzoites by immunoblot to select the most
      relevant antigenic bands to be used for qualitative serodiagnosis of acquired
      toxoplasmosis. We selected five relevant bands (98, 36, 33, 32 and 21 kDa) with
      soluble antigens and four relevant bands (42, 35, 32 and 30 kDa) with membrane
      antigens which gave high sensitivity and/or specificity in immunodiagnosis. The
      association on the same blot of at least three of the five relevant bands in the
      soluble antigen immunoblot showed the highest sensitivity/specificity
      (97.4%/99.0%, respectively). Our results indicate that immunoblot using soluble
      tachyzoite extract with simultaneous detection of at least three of the five
      bands (98, 36, 33, 32 and 21 kDa) represents a valuable test for serodiagnosis of
      acquired toxoplasmosis and should be further evaluated as a confirmatory test for
      sera which give discrepant results in quantitative assays.

PMID- 25384439
TI  - H9N2 influenza virus in China: a cause of concern.
AB  - The recent human infection with avian influenza virus revealed that H9N2
      influenza virus is the gene donor for H7N9 and H10N8 viruses infecting humans.
      The crucial role of H9N2 viruses at the animal-human interface might be due to
      the wide host range, adaptation in both poultry and mammalian, and extensive gene
      reassortment. As the most prevalent subtype of influenza viruses in chickens in
      China, H9N2 also causes a great economic loss for the poultry industry, even
      under the long-term vaccination programs. The history, epidemiology, biological
      characteristics, and molecular determinants of H9N2 influenza virus are reviewed
      in this paper. The contribution of H9N2 genes, especially RNP genes, to the
      infection of humans needs to be investigated in the future. 

PMID- 25384441
TI  - No booster dose for yellow fever vaccination: what are the consequences for the
      activity of vaccination in travel clinics?
AB  - In April 2013, the Strategic Advisory Group of Experts (SAGE) on immunization
      stated that a single dose of yellow fever (YF) vaccine is sufficient in the
      general population to confer a lifelong protection against YF. When the period of
      validity of the International Certificate of Vaccination (ICV) will be extended
      to a lifetime in June 2016, no booster dose will be needed. The objective of this
      prospective study was to determine the potential impact of the SAGE
      recommendations on the vaccination activity of our travel clinics. We showed that
      among 1,037 subjects seen in our three travel clinics for a YF vaccination in
      2013, about 32.3% went for a booster dose that is no longer useful according to
      the SAGE. A drop in vaccination activity has to be expected by travel clinics in
      the next years, and changes in daily exercise have to be anticipated, as YF
      vaccination is a large part of the regular work of many healthcare providers
      specialized in travel medicine. 

PMID- 25384442
TI  - Staff morale is dropping as NHS money pressures grow, says King's Fund report.

PMID- 25384443
TI  - Interobserver agreement on histopathological lesions in class III or IV lupus
      nephritis.
AB  - BACKGROUND AND OBJECTIVES: To treat lupus nephritis effectively, proper
      identification of the histologic class is essential. Although the classification
      system for lupus nephritis is nearly 40 years old, remarkably few studies have
      investigated interobserver agreement. Interobserver agreement among
      nephropathologists was studied, particularly with respect to the recognition of
      class III/IV lupus nephritis lesions, and possible causes of disagreement were
      determined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A link to a survey
      containing pictures of 30 glomeruli was provided to all 360 members of the Renal
      Pathology Society; 34 responses were received from 12 countries (a response rate
      of 9.4%). The nephropathologist was asked whether glomerular lesions were present
      that would categorize the biopsy as class III/IV. If so, additional parameters
      were scored. To determine the interobserver agreement among the participants,
      kappa or intraclass correlation values were calculated. The intraclass
      correlation or kappa-value was also calculated for two separate levels of
      experience (specifically, nephropathologists who were new to the field or
      moderately experienced [less experienced] and nephropathologists who were highly
      experienced). RESULTS: Intraclass correlation for the presence of a class III/IV
      lesion was 0.39 (poor). The kappa/intraclass correlation values for the
      additional parameters were as follows: active, chronic, or both: 0.36; segmental
      versus global: 0.39; endocapillary proliferation: 0.46; influx of inflammatory
      cells: 0.32; swelling of endothelial cells: 0.46; extracapillary proliferation:
      0.57; type of crescent: 0.46; and wire loops: 0.35. The highly experienced
      nephropathologists had significantly less interobserver variability compared with
      the less experienced nephropathologists (P=0.004). CONCLUSIONS: There is
      generally poor agreement in terms of recognizing class III/IV lesions. Because
      experience clearly increases interobserver agreement, this agreement may be
      improved by training nephropathologists. These results also underscore the
      importance of a central review by experienced nephropathologists in clinical
      trials.

PMID- 25384444
TI  - Phosphorylation of the ribosomal protein S6, a marker of mTOR (mammalian target
      of rapamycin) pathway activation, is strongly increased in hypertrophic scars and
      keloids.

PMID- 25384445
TI  - A novel method to assess primary stability of press-fit acetabular cups.
AB  - Initial stability is an essential prerequisite to achieve osseointegration of
      press-fit acetabular cups in total hip replacements. Most in vitro methods that
      assess cup stability do not reproduce physiological loading conditions and use
      simplified acetabular models with a spherical cavity. The aim of this study was
      to investigate the effect of bone density and acetabular geometry on cup
      stability using a novel method for measuring acetabular cup micromotion. A press
      fit cup was inserted into Sawbones((r)) foam blocks having different densities to
      simulate normal and osteoporotic bone variations and different acetabular
      geometries. The stability of the cup was assessed in two ways: (a) measurement of
      micromotion of the cup in 6 degrees of freedom under physiological loading and
      (b) uniaxial push-out tests. The results indicate that changes in bone substrate
      density and acetabular geometry affect the stability of press-fit acetabular
      cups. They also suggest that cups implanted into weaker, for example,
      osteoporotic, bone are subjected to higher levels of micromotion and are
      therefore more prone to loosening. The decrease in stability of the cup in the
      physiological model suggests that using simplified spherical cavities to model
      the acetabulum over-estimates the initial stability of press-fit cups. This novel
      testing method should provide the basis for a more representative protocol for
      future pre-clinical evaluation of new acetabular cup designs. 

PMID- 25384446
TI  - Study on the anti-gout activity of chlorogenic acid: improvement on hyperuricemia
      and gouty inflammation.
AB  - Gout is a metabolic disorder associated with hyperuricemia resulting in the
      deposition of monosodium urate (MSU) crystals in joints and tissues. Lowering
      serum uric acid (Sur) levels and anti-inflammation are highly essential in
      treating gout. Chlorogenic acid (CA), as one of the most abundant polyphenols in
      the Chinese medicines, has been rarely reported to have an anti-gout effect. The
      model of potassium oxonate (PO)-induced hyperuricemia in mice and MSU crystal
      induced inflammation in rats has been established in this study. The potential
      beneficial effects and mechanisms of CA on hyperuricemia and gouty arthritis were
      elucidated. The results demonstrated that CA significantly decreased the Sur
      level by inhibiting the xanthine oxidase (XOD) activity but not increasing the
      urinary uric acid (Uur) level. In addition, CA also exhibited the effect of
      suppressing paw swelling. Further investigation indicated that CA improved the
      symptoms of inflammation induced by MSU crystals by inhibiting the production of
      proinflammatory cytokines including interleukin-1beta (IL-1beta), interleukin-6
      (IL-6), and tumor necrosis factor-alpha (TNF-alpha). The present study suggests
      that CA may have a considerable potential for development as an anti-gouty
      arthritis agent for clinical application. 

PMID- 25384447
TI  - Hepatoprotective and anti-oxidant activities of Glossogyne tenuifolia against
      acetaminophen-induced hepatotoxicity in mice.
AB  - The present study investigated the anti-oxidative and hepatoprotective effects of
      Glossogyne tenuifolia (GT) Cassini, against acetaminophen-induced acute liver
      injury in BALB/c mice. The extracts of GT by various solvents (hot water, 50%
      ethanol and 95% ethanol) were compared for their 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radical scavenging activity, reducing power, total phenolic content, and
      total anti-oxidant capacity. The results showed that hot water (HW) extracts of
      GT contained high levels of phenolics and exerted an excellent anti-oxidative
      capacity; thus, these were used in the animal experiment. The male BALB/c mice
      were randomly divided into control group, acetaminophen (APAP) group, positive
      control group and two GT groups at low (GT-L) and high (GT-H) dosages. The
      results showed that mice treated with GT had significantly decreased serum levels
      of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). GT-H
      increased glutathione levels and the ratios of reduced glutathione and oxidized
      glutathione (GSH/GSSG) in the liver, and inhibited serum and lipid peroxidation.
      This experiment was the first to determine phenolic compounds, chlorogenic acid
      and luteolin-7-glucoside in HW extract of GT. In conclusion, HW extract of GT may
      have potential anti-oxidant capacity and show hepatoprotective capacities in APAP
      induced liver damaged mice. 

PMID- 25384448
TI  - Analgesic effect of manual acupuncture and laser acupuncture for lateral
      epicondylalgia: a systematic review and meta-analysis.
AB  - Lateral epicondylalgia is a common orthopedic disorder. In traditional Chinese
      medicine, acupuncture is often used for treating lateral epicondylalgia. Laser
      acupuncture, compared with manual acupuncture, has more advantages because it is
      painless, aseptic and safe. However, the analgesic effect of manual acupuncture
      and laser acupuncture on lateral epicondylalgia has rarely been explored. We
      conducted a systematic review and meta-analysis to compare the analgesic effect
      of laser acupuncture and manual acupuncture for the treatment of lateral
      epicondylalgia. We investigated studies published in the Medline, PubMed, and
      CINAHL databases from January 1980 to December 2013. This review included 9
      randomized articles. Six of them examined manual acupuncture and the others
      focused on laser acupuncture. We analyzed the meta-analysis results regarding the
      analgesic effect of the treatment, and observed substantial differences in 4
      articles related to manual acupuncture. Manual acupuncture is effective in short
      term pain relief for the treatment of lateral epicondylalgia; however, its long
      term analgesic effect is unremarkable. A suitable acupuncture point and depth can
      be used to treat lateral epicondylalgia. Manual acupuncture applied on lateral
      epicondylalgia produced stronger evidence of an analgesic effect than did laser
      acupuncture, and further study on the analgesic effect of laser acupuncture is
      required. 

PMID- 25384449
TI  - Astragaloside improves outcomes of traumatic brain injury in rats by reducing
      microglia activation.
AB  - Astragaloside (AST) is traditionally prescribed for the prevention and treatment
      of cerebrovascular diseases. We directly tested the therapeutic effects of AST in
      a rat model of traumatic brain injury (TBI). One hour after the onset of TBI rats
      were given Saline (1 ml/kg) or AST (20-80 mg/kg) via i.p. injection. AST causes
      the attenuation of TBI-induced cerebral contusion, neuronal apoptosis, and
      neurological motor dysfunction. TBI-induced microglial activation evidenced by
      the morphological transformation of microglia (or ameboid microglia) and the
      microglial overexpression of tumor necrosis factor-alpha was reduced by AST. Our
      results indicate that AST may protect against brain contusion and neuronal
      apoptosis after TBI by attenuating microglia activation in male rats. 

PMID- 25384450
TI  - Glomus-like bodies within a neurofibroma: a novel neoplasm arising in
      neurofibromatosis type 1 or a coincidence?
AB  - Neurofibromatosis type 1 is a relatively common genetic disorder with variable
      phenotypes. Tumors with features of both glomus tumors and neurofibromas are
      exceedingly rare in literature. Herein, we report a not yet described neoplasm
      with features of both a glomangioma/glomus tumor and a neurofibroma arising in a
      patient with segmental neurofibromatosis. Our case report supports the theory of
      a common lineage/ancestor cell between neurofibromas and glomus tumors and adds
      it to the spectrum of neoplasms that may arise in the setting of Von
      Recklinghausen's disease. 

PMID- 25384451
TI  - Spontaneous resolution of peripapillary retinoschisis associated with
      glaucomatous optic neuropathy.

PMID- 25384452
TI  - The peroneocuboid joint: morphogenesis and anatomical study.
AB  - The peroneocuboid joint, between the peroneus longus tendon and the cuboid bone,
      has not been anatomically well-defined and no embryological study has been
      published. Furthermore, the ossification of the os peroneum (a sesamoid inside
      the peroneus longus tendon) and its associated pathology has been considered to
      be generated by orthostatic and/or mechanical loads. A light microscopy analysis
      of serially sectioned human embryonic and fetal feet, the analysis of human adult
      feet by means of standard macroscopic dissection, X-ray and histological
      techniques have been carried out. The peroneus longus tendon was fully visible
      until its insertion in the 1st metatarsal bone already at embryonic stage 23 (56
      57 days). The peroneocuboid joint cavity appeared at the transition of the
      embryonic to the fetal period (8-9th week of gestation) and was independent of
      the proximal synovial sheath. The joint cavity extended from the level of the
      calcaneocuboid joint all the way to the insertion of the peroneus longus tendon
      in the 1st metatarsal bone. The frenular ligaments, fixing the peroneus longus
      tendon to the 5th metatarsal bone or the long calcaneocuboid ligament, developed
      in the embryonic period. The peroneus longus tendon presented a thickening in the
      area surrounding the cuboid bone as early as the fetal period. This thickening
      may be considered the precursor of the os peroneum and was similar in shape and
      in size relation to the tendon, to the os peroneum observed in adults. To the
      best of our knowledge, this is the first study to show that the os peroneum,
      articular facets of the peroneus longus tendon and cuboid bone, the peroneocuboid
      joint and the frenular ligaments appear during the embryonic/fetal development
      period and therefore they can not be generated exclusively by orthostatic and
      mechanical forces or pathological processes. 

PMID- 25384453
TI  - A preliminary investigation into theory of mind and attributional style in adults
      with grandiose delusions.
AB  - INTRODUCTION: A preliminary cognitive model of grandiose delusions has been put
      forward suggesting that persecutory and grandiose delusions shared distinct, yet
      overlapping psychological processes. This study aims to test this model and
      hypothesises that participants experiencing grandiose delusions may demonstrate a
      theory of mind (ToM) impairment and differences in attributional style compared
      to a control group. METHODS: A cross-sectional design compared the performance of
      18 individuals with grandiose delusions to a control group of 14 participants
      with depression. ToM was measured using a non-verbal joke appreciation task and a
      verbal stories task. Attributional style was measured using the internal,
      personal and situational attributions questionnaire. RESULTS: Participants
      experiencing grandiose delusions performed significantly worse on both ToM tasks
      compared to controls. Furthermore, these participants provided significantly more
      atypical answers when explaining the joke behind the ToM cartoons. No differences
      for subjective funniness ratings or attributional style were found. CONCLUSIONS:
      This preliminary study indicated participants experiencing grandiose delusions
      have ToM impairments which may contribute to the maintenance of this symptom.

PMID- 25384456
TI  - Quantification of ion-pairing effects on the nucleophilic reactivities of benzoyl
      and phenyl-substituted carbanions in dimethylsulfoxide.
AB  - Second-order rate constants for the reactions of acceptor-substituted phenacyl
      (PhCO?CH(-) ?Acc) and benzyl anions (Ph?CH(-) ?Acc) with diarylcarbenium ions and
      quinone methides (reference electrophiles) have been determined in
      dimethylsulfoxide (DMSO) solution at 20  degrees C. By studying the kinetics in
      the presence of variable concentrations of potassium, sodium and lithium salts
      (up to 10(-2)  mol L(-1) ), the influence of ion-pairing on the reaction rates
      was examined. As the concentration of K(+) did not have any influence on the rate
      constants at carbanion concentrations in the range of 10(-4) -10(-3)  mol L(-1) ,
      the acquired rate constants could be assigned to the reactivities of the free
      carbanions. The counter ion effects increase, however, in the series K(+) <Na(+)
      <Li(+) , and the sensitivity of the carbanion reactivities toward variation of
      the counter ion strongly depends on the structure of the carbanions. The
      reactivity parameters N and sN of the free carbanions were derived from the
      linear plots of log k2 against the electrophilicity parameters E of the reference
      electrophiles, according to the linear-free energy relationship log k2 (20 
      degrees C)=sN (N+E). These reactivity parameters can be used to predict absolute
      rate constants for the reactions of these carbanions with other electrophiles of
      known E parameters. 

PMID- 25384455
TI  - Abiotic stress protection by ecologically abundant dimethylsulfoniopropionate and
      its natural and synthetic derivatives: insights from Bacillus subtilis.
AB  - Dimethylsulfoniopropionate (DMSP) is an abundant osmolyte and anti-stress
      compound produced primarily in marine ecosystems. After its release into the
      environment, microorganisms can exploit DMSP as a source of sulfur and carbon, or
      accumulate it as an osmoprotectant. However, import systems for this
      ecophysiologically important compatible solute, and its stress-protective
      properties for microorganisms that do not produce it are insufficiently
      understood. Here we address these questions using a well-characterized set of
      Bacillus subtilis mutants to chemically profile the influence of DMSP import on
      stress resistance, the osmostress-adaptive proline pool and on osmotically
      controlled gene expression. We included in this study the naturally occurring
      selenium analogue of DMSP, dimethylseleniopropionate (DMSeP), as well as a set of
      synthetic DMSP derivatives. We found that DMSP is not a nutrient for B. subtilis,
      but it serves as an excellent stress protectant against challenges conferred by
      sustained high salinity or lasting extremes in both low and high growth
      temperatures. DMSeP and synthetic DMSP derivatives retain part of these stress
      protective attributes, but DMSP is clearly the more effective stress protectant.
      We identified the promiscuous and widely distributed ABC transporter OpuC as a
      high-affinity uptake system not only for DMSP, but also for its natural and
      synthetic derivatives. 

PMID- 25384454
TI  - Issues in interpreting the in vivo activity of Aurora-A.
AB  - INTRODUCTION: Based on its role as a mitotic regulatory kinase, overexpressed and
      associated with aneuploidy in cancer, small-molecule inhibitors have been
      developed for Aurora-A (AURKA) kinase. In preclinical and clinical assessments,
      these agents have shown efficacy in inducing stable disease or therapeutic
      response. In optimizing the use of Aurora-A inhibitors, it is critical to have
      robust capacity to measure the kinase activity of Aurora-A in tumors. AREAS
      COVERED: We provide an overview of molecular mechanisms of mitotic and non
      mitotic activation of Aurora-A kinase, and interaction of Aurora-A with its
      regulatory partners. Typically, Aurora-A activity is measured by use of phospho
      antibodies targeting an autophosphorylated T288 epitope. However, recent studies
      have identified alternative means of Aurora-A activation control, including
      allosteric regulation by partners, phosphorylation on alternative activating
      residues (S51, S98), dephosphorylation on inhibitory sites (S342) and T288
      phosphorylation by alternative kinases such as Pak enzymes. Additional work has
      shown that the relative abundance of Aurora-A partners can affect the activity of
      Aurora-A inhibitors, and that Aurora-A activation also occurs in interphase
      cells. EXPERT OPINION: Taken together, this work suggests the need for
      comprehensive analysis of Aurora-A activity and expression of Aurora-A partners
      in order to stratify patients for likely therapeutic response.

PMID- 25384457
TI  - Flow dependence of specific airway resistance and diagnostic of asthma in
      children.
AB  - Panting majors turbulent flow and contribution of larger airways to the
      measurement of specific airway resistance (sRaw). The hypothesis was tested that
      the difference between asthmatic and healthy children is enhanced by narrowing
      the flow interval to compute sRaw. sRaw was measured during panting in 40
      asthmatic and 25 healthy children and computed using all data points (full scale
      flow) and limited to the flow intervals +/- 1L/sec and +/- 0.5 L/sec. sRaw was
      not different between asthmatics (0.87 +/- 0.20 kPa.s) and controls (0.80 +/-
      0.25 kPa.s) when computed full scale, while it was significantly larger in
      asthmatics than controls within +/- 1L/sec (0.77 +/- 0.16 kPa.s vs 0.65 +/- 0.15
      kPa.s, P < 0.004) or +/- 0.5 L/sec (0.77 +/- 0.21 kPa.s vs 0.61 +/- 0.17 kPa.s, P
      < 0.002). On the other hand, the within subject coefficient of variation was
      significantly larger when sRaw was computed within +/- 1L/sec (13.7 +/- 7.2%) or
      +/- 0.5 L/sec (28.3 +/- 18.1%) than full scale (11.0 +/- 6.7%), respectively P <
      0.002 and P < 0.0001. It is concluded that narrowing the flow interval to compute
      sRaw is associated with better discrimination between asthma and health in
      children, although the short term variability of sRaw is increased.

PMID- 25384458
TI  - Preparation, characterization, and DNA interaction studies of cationic europium
      luminescent copolymer.
AB  - This paper proposed a simple synthetic strategy towards a novel cationic europium
      luminescent copolymer, poly(METAC-co-NIPAm-co-Eu(AA)3Phen) (PMNEu), and
      investigation about their complexation ability with DNA. In this approach, first,
      Eu(AA)3Phen complex monomer containing Eu(3+), acrylic acid (AA), and 1,10
      phenanthroline (Phen) was synthesized, and subsequently, free radical
      copolymerization of Eu(AA)3Phen complex monomer with other two functional
      monomers, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (METAC) and N
      isopropylarylamide (NIPAm), was carried out in methanol using
      azodiisobutyronitrile (AIBN) as the initiator. (1)HNMR, GPC, fluorescence
      spectroscopy, UV-vis spectroscopy, and TEM were used to investigate the chemical
      structures, molecular weight and molecular weight distribution, fluorescence
      properties, UV spectra, and morphologies of PMNEu copolymer, respectively.
      Furthermore, the interaction of PMNEu with DNA was also studied with fluorescence
      spectroscopy, UV-vis spectroscopy, and agarose gel electrophoresis. These results
      indicated that PMNEu could interact with DNA via an electrostatic bonding mode
      and the bonding constant was 2.2 * 10(5) L/mol. Additionally, TEM observation
      showed that pure PMNEu formed micelles in water solution, while the size
      controllable aggregations of PMNEu with DNA were obtained when PMNEu was mixed
      with DNA at various concentration ratios. A good biocompability of PMNEu was
      demonstrated through in vitro cytotoxicity assays. 

PMID- 25384459
TI  - Alteration of the phenology of leaf senescence and fall in winter deciduous
      species by climate change: effects on nutrient proficiency.
AB  - Leaf senescence in winter deciduous species signals the transition from the
      active to the dormant stage. The purpose of leaf senescence is the recovery of
      nutrients before the leaves fall. Photoperiod and temperature are the main cues
      controlling leaf senescence in winter deciduous species, with water stress
      imposing an additional influence. Photoperiod exerts a strict control on leaf
      senescence at latitudes where winters are severe and temperature gains importance
      in the regulation as winters become less severe. On average, climatic warming
      will delay and drought will advance leaf senescence, but at varying degrees
      depending on the species. Warming and drought thus have opposite effects on the
      phenology of leaf senescence, and the impact of climate change will therefore
      depend on the relative importance of each factor in specific regions. Warming is
      not expected to have a strong impact on nutrient proficiency although a slower
      speed of leaf senescence induced by warming could facilitate a more efficient
      nutrient resorption. Nutrient resorption is less efficient when the leaves
      senesce prematurely as a consequence of water stress. The overall effects of
      climate change on nutrient resorption will depend on the contrasting effects of
      warming and drought. Changes in nutrient resorption and proficiency will impact
      production in the following year, at least in early spring, because the
      construction of new foliage relies almost exclusively on nutrients resorbed from
      foliage during the preceding leaf fall. Changes in the phenology of leaf
      senescence will thus impact carbon uptake, but also ecosystem nutrient cycling,
      especially if the changes are consequence of water stress. 

PMID- 25384460
TI  - Characterization of plasmid pXL100 from Amycolatopsis orientalis HCCB10007 and
      construction of a shuttle vector.
AB  - Many strains of Amycolatopsis, such as Amycolatopsis orientalis, A. balhimycina,
      and A. mediterranei, are important antibiotic producers. Three indigenous
      plasmids, pMEA100, pMEA300, and pA387, found in this genus have been sequenced.
      However, only some vectors based on pA387 have been widely applied in
      Amycolatopsis research. An indigenous plasmid, pXL100, was isolated from the
      vancomycin producer A. orientalis HCCB10007. Sequence analysis of pXL100 revealed
      its total length to be 33,499 bp and GC content to be 68.9%. A 2830-bp fragment
      containing three ORFs has been identified as essential for replication in A.
      orientalis, but it has no significant similarity to any known replicons. A
      vector, pLYZW7-3, was constructed based on the pXL100 replicon and could be
      transferred into A. mediterranei and A. orientalis by electroporation or
      conjugation with high frequency. A mutant with a disrupted gene was successfully
      complemented with the pLYZW7-3 vector, indicating that the vector is potentially
      useful in Amycolatopsis research. 

PMID- 25384461
TI  - Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep
      behavior disorder.
AB  - Hyperechogenicity of the substantia nigra visualized by transcranial sonography
      occurs in most Parkinson's disease (PD) patients. Idiopathic rapid eye movement
      (REM) sleep behavior disorder (IRBD) subjects eventually develop PD and other
      synucleinopathies. This study was undertaken to evaluate whether in IRBD,
      transcranial sonography identifies subjects who convert to PD and other
      synucleinopathies, and whether substantia nigra echogenic size changes with time.
      It was a prospective study in which 55 IRBD patients underwent transcranial
      sonography at baseline and were invited to follow-up after 5 years. Patients were
      assessed by the same experienced sonographer who was blinded to clinical data and
      baseline transcranial sonography results, and used the same equipment and
      adjustments. Twenty-one (38.2%) subjects were diagnosed with a synucleinopathy
      (PD in 11, dementia with Lewy bodies in nine, and multiple system atrophy in
      one). Sensitivity of baseline substantia nigra hyperechogenicity for the
      development of a synucleinopathy was 42.1%, specificity 67.7%, positive
      predictive value 44.4%, negative predictive value 65.6%, and relative risk 1.29.
      No differences were detected between the first and second examination in mean
      size of the substantia nigra (0.20 +/- 0.09 cm(2) vs. 0.19 +/- 0.07 cm(2) ; P =
      0.777) and in percentage of patients with substantia nigra hyperechogenicity
      (33.3% vs. 42.8%, P = 0.125). Transcranial sonography of the substantia nigra
      alone is not a useful tool to identify IRBD subjects at risk for the development
      of PD or a synucleinopathy after 5 years of follow-up. In IRBD, transcranial
      sonography cannot be used to monitor the degenerative process in the substantia
      nigra, because echogenicity size remains stable over time.

PMID- 25384462
TI  - CLUMSY VEIN, the Arabidopsis DEAH-box Prp16 ortholog, is required for auxin
      mediated development.
AB  - Pre-messenger RNA (pre-mRNA) splicing is essential in eukaryotic cells. In
      animals and yeasts, the DEAH-box RNA-dependent ATPase Prp16 mediates
      conformational change of the spliceosome, thereby facilitating pre-mRNA splicing.
      In yeasts, Prp16 also plays an important role in splicing fidelity. Conversely,
      PRP16 orthologs in Chlamydomonas reinhardtii and nematode do not have an
      important role in general pre-mRNA splicing, but are required for gene silencing
      and sex determination, respectively. Functions of PRP16 orthologs in higher
      plants have not been described until now. Here we show that the CLUMSY VEIN (CUV)
      gene encoding the unique Prp16 ortholog in Arabidopsis thaliana facilitates auxin
      mediated development including male-gametophyte transmission, apical-basal
      patterning of embryonic and gynoecium development, stamen development,
      phyllotactic flower positioning, and vascular development. cuv-1 mutation
      differentially affects splicing and expression of genes involved in auxin
      biosynthesis, polar auxin transport, auxin perception and auxin signaling. The
      cuv-1 mutation does not have an equal influence on pre-mRNA substrates. We
      propose that Arabidopsis PRP16/CUV differentially facilitates expression of
      genes, which include genes involved in auxin biosynthesis, transport, perception
      and signaling, thereby collectively influencing auxin-mediated development. 

PMID- 25384464
TI  - High strain in (K,Na)NbO3-based lead-free piezoceramics.
AB  - A high strain is important for practical applications of piezoelectric actuators.
      Here we reported a high strain in the (K,Na)NbO3 -based ceramics by doping
      alkaline earths or transition metals. The ceramics possess a high strain (~0.29%)
      as well as a large converse piezoelectric coefficient (d33*) up to 688 pm/V,
      which almost matches that of PZT4 ceramics. The obtained d33* is high for
      nontextured (K,Na)NbO3-based ceramics. In addition, a higher d33 value (340-407
      pC/N) was also attained in the ceramics. Enhanced d33 and d33* values of this
      work should be attributed to the multiphase coexistence's effect induced by
      alkaline earths or transition metals. We believe that our research can benefit
      the developments of (K,Na)NbO3 ceramics and widen their applications range. 

PMID- 25384463
TI  - Benefits of adding small financial incentives or optional group meetings to a web
      based statewide obesity initiative.
AB  - OBJECTIVE: To examine whether adding either small, variable financial incentives
      or optional group sessions improves weight losses in a community-based, Internet
      behavioral program. METHODS: Participants (N = 268) from Shape Up Rhode Island
      2012, a 3-month Web-based community wellness initiative, were randomized to:
      Shape Up+Internet behavioral program (SI), Shape Up+Internet program+incentives
      (SII), or Shape Up+Internet program+group sessions (SIG). RESULTS: At the end of
      the 3-month program, SII achieved significantly greater weight losses than SI
      (SII: 6.4% [5.1-7.7]; SI: 4.2% [3.0-5.6]; P = 0.03); weight losses in SIG were
      not significantly different from the other two conditions (SIG: 5.8% [4.5-7.1],
      P's >= 0.10). However, at the 12-month no-treatment follow-up visit, both SII and
      SIG had greater weight losses than SI (SII: 3.1% [1.8-4.4]; SIG: 4.5% [3.2-5.8];
      SI: 1.2% [-0.1-2.6]; P's <= 0.05). SII was the most cost-effective approach at
      both 3 (SII: $34/kg; SI: $34/kg; SIG: $87/kg) and 12 months (SII: $64/kg; SI:
      $140/kg; SIG: $113/kg). CONCLUSIONS: Modest financial incentives enhance weight
      losses during a community campaign, and both incentives and optional group
      meetings improved overall weight loss outcomes during the follow-up period.
      However, the use of the financial incentives is the most cost-effective approach.

PMID- 25384465
TI  - Evaluating the impact of high Pluronic(r) F68 concentrations on antibody
      producing CHO cell lines.
AB  - Pluronic(r) F68 (P-F68) is an important component of chemically-defined cell
      culture medium because it protects cells from hydrodynamic and bubble-induced
      shear in the bioreactor. While P-F68 is typically used in cell culture medium at
      a concentration of 1 g/L (0.1%), higher concentrations can offer additional shear
      protection and have also been shown to be beneficial during cryopreservation.
      Recent industry experience with variability in P-F68-associated shear-protection
      has opened up the possibility of elevated P-F68 concentrations in cell culture
      media, a topic that has not been previously explored in the context of industrial
      cell culture processes. Recognizing this gap, we first evaluated the effect of 1
      5 g/L P-F68 concentrations in shake flask cultures over ten 3-day passages for
      cell lines A and B. Increase in terminal cell density and cell size was seen over
      time at higher P-F68 concentrations but protein productivity was not impacted.
      Results from this preliminary screening study suggested no adverse impact of high
      P-F68 concentrations. Subsequently fed-batch bioreactor experiments were
      conducted at 1 and 5 g/L P-F68 concentrations with both cell lines where cell
      growth, viability, metabolism, and product quality were examined under process
      conditions reflective of a commercial process. Results from these bioreactor
      experiments confirmed findings from the preliminary screen and also indicated no
      impact of elevated P-F68 concentration on product quality. If additional shear
      protection is desired, either due to raw material variability, cell line
      sensitivity, or a high-shear cell culture process, our results suggest this can
      be accomplished by elevating the P-F68 concentration in the cell culture medium
      without impacting cell culture performance and product quality.

PMID- 25384466
TI  - Responsive aqueous foams.
AB  - Remarkable properties have emerged recently for aqueous foams, including
      ultrastability and responsiveness. Responsive aqueous foams refer to foams for
      which the stability can be switched between stable and unstable states with a
      change in environment or with external stimuli. Responsive foams have been
      obtained from various foam stabilizers, such as surfactants, proteins, polymers,
      and particles, and with various stimuli. Different strategies have been developed
      to design this type of soft material. We briefly review the two main approaches
      used to obtain responsive foams. The first approach is based on the
      responsiveness of the interfacial layer surrounding the gas bubbles, which leads
      to responsive foams. The second approach is based on modifications that occur in
      the aqueous phase inside the foam liquid channels to tune the foam stability. We
      will highlight the most sophisticated approaches, which use light, temperature,
      and magnetic fields and lead to switchable foam stability. 

PMID- 25384467
TI  - Expression analysis of five zebrafish RXFP3 homologues reveals evolutionary
      conservation of gene expression pattern.
AB  - Relaxin peptides exert different functions in reproduction and neuroendocrine
      processes via interaction with two evolutionarily unrelated groups of receptors:
      RXFP1 and RXFP2 on one hand, RXFP3 and RXFP4 on the other hand. Evolution of
      receptor genes after splitting of tetrapods and teleost lineage led to a
      different retention rate between mammals and fish, with the latter having more
      gene copies compared to the former. In order to improve our knowledge on the
      evolution of the relaxin ligands/receptors system and have insights on their
      function in early stages of life, in the present paper we analyzed the expression
      pattern of five zebrafish RXFP3 homologue genes during embryonic development. In
      our analysis, we show that only two of the five genes are expressed during
      embryogenesis and that their transcripts are present in all the developmental
      stages. Spatial localization analysis of these transcripts revealed that the gene
      expression is restricted in specific territories starting from early pharyngula
      stage. Both genes are expressed in the brain but in different cell clusters and
      in extra-neural territories, one gene in the interrenal gland and the other in
      the pancreas. These two genes share expression territories with the homologue
      mammalian counterpart, highlighting a general conservation of gene expression
      regulatory processes and their putative function during evolution that are
      established early in vertebrate embryogenesis.

PMID- 25384468
TI  - Injury. Biological treatments for musculoskeletal pathologies. Editorial.

PMID- 25384469
TI  - Meniscal repair possibilities using bone morphogenetic protein-7.
AB  - This study analysed the influence of bone morphogenetic protein-7 (BMP-7) on
      cells and meniscal structure. The effect of treatment with BMP-7 was assessed in
      vitro and in vivo in lesions in the avascular area of the meniscus. Cells were
      extracted from the outer and inner part of eight menisci of four 2-year-old
      merino sheep. The menisci were digested with a collagenase mix, and meniscus
      cells of the synovium, vascular area and avascular area were extracted. The
      expression of genes for collagen (Col1 and Col2A), matrix metalloproteinases (MMP
      2 and MMP-13) and aggrecan was analysed by real time quantitative polymerase
      chain reaction (qPCR) at baseline and after incubation with BMP-7. Eight sheep
      aged 2 years and weighing 35-40 kg were used for the in vivo study. Surgery was
      performed in both knees of every animal. Two holes were made in the avascular
      area of the medial meniscus of both knees and filled using Putty((r)) (control
      groups) or OP-1 Putty((r)), which comprises BMP-7 mixed with a cellulose putty
      carrier (experimental groups). Animals were sacrificed at 6, 12 and 25 weeks.
      Adding BMP-7 to vascular cells of the meniscus was associated with a 15-fold
      increase in Col2A expression and a 78-fold increase in BMP-7 expression. BMP-7
      inhibited MMP-2 and MMP-13 expression. Adding BMP-7 to synovial cells inhibited
      the expression of Col1, doubled the expression of Col2A and reduced the
      expression of BMP-7; the expression of MMP-2 was inhibited, while that of MMP-13
      was increased three-fold. Incubation of cells from the avascular region with BMP
      7 was associated with a 2.4-fold increase in Col1 expression, and a 4.4-fold
      increase in Col2A expression compared with the control. The expression of MMP-2
      and BMP-7 was inhibited. In the in vivo study, treatment of the holes in the
      avascular area of the meniscus with BMP-7 was associated with an important cell
      presence inside the holes and the appearance of fibrous tissue after 12 weeks;
      these features were not seen in the control groups. BMP-7 may be a suitable
      growth factor for stimulation of meniscal cell and collagen formation. 

PMID- 25384470
TI  - Peripheral nerve regeneration after experimental section in ovine radial and
      tibial nerves using synthetic nerve grafts, including expanded bone marrow
      mesenchymal cells: morphological and neurophysiological results.
AB  - The standard treatment of peripherical nerve injuries with substance gap is to
      introduce the nerve free extremes in a biodegradable tube which, as a biocamera,
      allows the continuity of the nerve, promote the neuroconduction and save the
      lesion from the surrounding fibrosis. However, this procedure has not any direct
      effect on the neuroregeneration nor to resolve high severe lesions. The
      mesenchymal stem cells (MSC) can derivate "in vitro" in different lineages,
      including Schwann cells. Different studies have shown MSC can promote the nerve
      regeneration in rodents, dogs and primates. Moving to the human clinical
      application requires the procedure standardization, including the optimal cell
      dose which we have to use. In the sheep model animal we performed a study of 1
      cm. nerve section-ressection and repair with a NeurolacTM biocamera, in whose gap
      we applied between 30 to 50*10(6) MSC from cancellous bone, all of them selected
      and cultured with GMP procedures. The results were compared with controls (saline
      serum +/- platelet-rich plasma). We used radial nerve (sensitive) and tibial
      nerve (motor) from 7 sheep. In the first step we performed the surgical lesion
      and bone marrow aspiration, and in 3 weeks we performed the surgical repair. 3
      sheep were sacrificed in 3 months, and 4 sheep in 6 months. In all surgeries we
      performed a neurophysiological register. When we obtained the tissue samples, we
      performed an histological, immunohistiquimical and morphometrical study. The
      recovery percentage was defined comparing the axonal density from the proximal
      and distal lesion margins. The 3 months samples results were wrong. In 6 months
      samples results we observed a significative myelined nervous fibers and
      conduction increasing, in front of controls, both radial and tibial nerves. These
      results suggest the MSC application in biodegradable scaffold in nerve injuries
      promotes good results in terms of regeneration and functional recovery. 

PMID- 25384471
TI  - Application of adipose tissue-derived stem cells in a rat rotator cuff repair
      model.
AB  - INTRODUCTION: Healing tissue of the rotator cuff does not regenerate the native
      enthesis; fibrovascular scar tissue is formed instead and this has less
      favourable biomechanical properties. The purpose of this study was to determine
      if the application of adipose tissue-derived stem cells (ASCs) could improve
      biomechanical and histological properties of the repair. MATERIAL AND METHODS:
      Fifty Sprague-Dawley rats underwent detachment and repair of the supraspinatus
      tendon, 32 for the biomechanical study and 18 for the histological examination.
      Animals were randomised in two groups to receive either a collagen carrier alone
      (untreated group) or the carrier plus 2*10(6) ASCs (ASCs group). A control group
      (suture only) was also included for the histological examination. The animals
      were sacrificed at 2 and 4 weeks for the biomechanical study and at 24 hours, and
      1 and 4 weeks for the histological study. Maximum load failure energy, elastic
      energy, mechanical deformation, stiffness and absorbed energy were measured.
      Immunofluorescence testing was conducted to show the presence of ASCs in the
      repair area. RESULTS: There were no differences between the untreated group and
      the ASCs group in any of the biomechanical variables at the 2- and 4-week time
      points. The mechanical deformation before failure was higher for the ASCs group
      compared with the untreated group at 2 weeks and 4 weeks (p=0.09), as was the
      absorbed energy (p=0.06). Differences in maximum load to failure between 2 and 4
      weeks were significant for the untreated group (p=0.04) but not for the ASCs
      group (p=0.17). Histological examination showed less acute inflammation with
      diminished presence of oedema and neutrophils in the ASCs group. There were no
      differences in the orientation of collagen fibres between groups at either time
      point. In the ASCs group, collagen was present only at the last time point.
      CONCLUSION: The application of ASCs in a rat rotator cuff repair model did not
      improve the biomechanical properties of the tendon-to-bone healing. However, the
      ASCs group showed less inflammation, which may lead to a more elastic repair and
      less scarred healing.

PMID- 25384472
TI  - Investigating a potential biological treatment to prevent pathological fractures
      caused by unicameral bone cysts in children under 8 years.
AB  - INTRODUCTION: There is no consensus on when and how to treat unicameral bone
      cysts (UBCs), partly because of a lack of knowledge of the aetiology. PURPOSE: To
      review the different treatment techniques for UBCs and to describe our results
      with a single injection of autogenous bone marrow (BM) mixed with demineralised
      bone matrix (DBM) in very young children. PATIENTS AND METHODS: We reviewed five
      patients under the age of 8 years with UBCs treated by percutaneous aspiration
      and a single injection of BM associated with DBM. The cyst was located in the
      proximal humerus in four patients and in the proximal femur in one patient.
      Assessment of the need for surgery was based on the clinical and radiographic
      suspicion of new pathological fractures. The administration of a second
      injection, when necessary, was based on the surgeon's judgement regarding the
      risk of fracture. The mean follow-up after first injection was 41 months.
      RESULTS: There were no complications related to the procedure, except a non
      displaced fracture, which healed without problems. All patients were pain free
      and progressively resumed their activities without restriction until a new
      fracture occurred in two cases. According to Capanna's classification, only one
      case healed completely (grade 1), one lesion was classified as grade 2, and there
      were three recurrences at 11, 12 and 27 months after initial treatment (grade 3).
      The final outcome was treatment failure for three out of the five patients. Two
      patients were treated with a second injection and one patient is waiting for
      surgery. CONCLUSION: A single injection of aspirated autogenous BM mixed with DBM
      in very young children with active UBCs at risk of fracture is very simple,
      comfortable and safe. Nevertheless, the results seem to be unpredictable and are
      probably more dependent on the natural evolution of the cyst than on the
      treatment. Further comparative studies with larger sample numbers are needed.

PMID- 25384473
TI  - Comparison between two different platelet-rich plasma preparations and control
      applied during anterior cruciate ligament reconstruction. Is there any evidence
      to support their use?
AB  - INTRODUCTION: To compare the clinical, analytical and graft maturation effects of
      two different platelet-rich plasma (PRP) preparations applied during anterior
      cruciate ligament (ACL) reconstruction. MATERIALS AND METHODS: A total of 150
      patients with ACL disruption were included in the study. Arthroscopic ACL
      reconstruction with patellar tendon allograft was conducted on all knees using
      the same protocol. One hundred patients were prospectively randomised to either a
      group to receive double-spinning platelet-enriched gel (PRP) with leukocytes
      (n=50) or to a non-gel group (n=50). Finally, we included 50 patients treated
      with a platelet-rich preparation from a single-spinning procedure (PRGF
      Endoret((r)) Technology) without leukocytes. Inflammatory parameters, including C
      reactive protein (CRP) and knee perimeters (PER), were measured 24 hours and 10
      days after surgery. Postoperative pain score (visual analogue score [VAS]) was
      recorded the day after surgery. Follow-up visits occurred postoperatively at 3,
      6, and 12 months. The International Knee Documentation Committee scale (IKDC) was
      included to compare functional state, and MRI was conducted 6 months after
      surgery. RESULTS: The PRGF group showed a statistically significant improvement
      in swelling and inflammatory parameters compared with the other two groups at 24
      hours after surgery (p<0.05). The results did not show any significant
      differences between groups for MRI and clinical scores. CONCLUSIONS: PRGF used in
      ACL allograft reconstruction was associated with reduced swelling; however, the
      intensity and uniformity of the graft on MRI were similar in the three groups,
      and there was no clinical or pain improvement compared with the control group.
      LEVEL OF EVIDENCE: II.

PMID- 25384474
TI  - Bone marrow mesenchymal stem cell aspirates from alternative sources: is the knee
      as good as the iliac crest?
AB  - INTRODUCTION: The most common method to obtain human mesenchymal stem cells
      (MSCs) is bone marrow aspiration from the iliac crest, but MSCs have also been
      isolated from different bones. The main purpose of this study was to compare bone
      marrow MSCs aspirated from the metaphysis of the distal femur and the proximal
      tibia with those obtained from the iliac crest, and to determine whether these
      locations represent potential alternative sources of MSCs for research and
      clinical application. MATERIALS AND METHODS: Bone marrow was aspirated from the
      iliac crest and the metaphysis of the distal femur and the proximal tibia during
      total knee arthroplasty in 20 patients. The aspirates were centrifuged by density
      gradient, then mononucleated cell (MNC) concentration in the different aspirates
      was determined using a Coulter counter. MSCs were isolated, cultivated and
      characterised by their immunophenotype and by their in vitro potential for
      differentiation into osteoblasts, chondroblasts and adipocytes in specific media.
      Expansion and cell viability were quantified using trypan blue staining and cell
      counting with a haemocytometer (Neubauer chamber). The three sources were
      compared in terms of MNC concentration, viability of the cultures and presence of
      MSC using the Wilcoxon test. RESULTS: MNC concentration was significantly higher
      in the iliac crest (10.05 Millions/ml) compared with the femur (0.67 Millions/ml)
      and tibia (1.7 Millions/ml). Culture success rates were 90%, 71% and 47% for MSCs
      from the iliac crest, femur and tibia, respectively. Flow cytometry analysis
      showed the presence of CD90+, CD105+, CD73+, VEGF+, CD71+, HLA-DR-, CD45-, CD34-,
      CD19-, and CD14- cells. The immunophenotype pattern of MSCs was similar for the
      three locations. Trilineage differentiation was achieved with all samples.
      CONCLUSIONS: MSCs can be found in bone marrow from the metaphysis of both the
      distal femur and the proximal tibia. The phenotype and differentiation potential
      of these cells are similar to those of bone marrow MSCs from the iliac crest.
      Bone marrow aspiration from these locations is a relatively easy and safe
      alternative to that from the iliac crest for obtaining MSCs. Further study is
      required to assess whether the concentrations of MSCs obtained from these sources
      are sufficient for one-step therapeutic purposes.

PMID- 25384475
TI  - Muscle repair: platelet-rich plasma derivates as a bridge from spontaneity to
      intervention.
AB  - Muscle injuries account for between 10% and 55% of all sporting injuries.
      Although the skeletal muscle is a plastic organ capable of responding efficiently
      to environmental changes, the appropriate treatment of muscle injuries remains a
      daunting clinical challenge in sports medicine. There is considerable evidence to
      indicate that growth factors, such as transforming growth factor-beta (TGFbeta),
      hepatocyte growth factor (HGF) or insulin-like growth factor (IGF), and fibrin
      matrix are key in cellular events required for muscle repair and regeneration,
      namely myogenesis, angiogenesis and fibrogenesis. An innovative biological
      approach to the treatment of muscle injuries is the application of Plasma Rich in
      Growth Factors (PRGF) in intramuscular infiltrations. PRGF delivers growth
      factors, cytokines and adhesive proteins present in platelets and plasma, as well
      as other biologically-active proteins conveyed by the plasma, such as fibrinogen,
      prothrombin and fibronectin. This autologous, mimetic biomaterial embedded with a
      pool of growth factors acts as a smart dynamic scaffold, and should be applied
      taking into account a biological approach. A clinical trial is required to assess
      the functional repair outcome of PRGF infiltrations in muscle injuries. 

PMID- 25384476
TI  - HtrC is involved in proteolysis of YpeB during germination of Bacillus anthracis
      and Bacillus subtilis spores.
AB  - Bacterial endospores can remain dormant for decades yet can respond to nutrients,
      germinate, and resume growth within minutes. An essential step in the germination
      process is degradation of the spore cortex peptidoglycan wall, and the SleB
      protein in Bacillus species plays a key role in this process. Stable
      incorporation of SleB into the spore requires the YpeB protein, and some evidence
      suggests that the two proteins interact within the dormant spore. Early during
      germination, YpeB is proteolytically processed to a stable fragment. In this
      work, the primary sites of YpeB cleavage were identified in Bacillus anthracis,
      and it was shown that the stable products are comprised of the C-terminal domain
      of YpeB. Modification of the predominant YpeB cleavage sites reduced proteolysis,
      but cleavage at other sites still resulted in loss of full-length YpeB. A B.
      anthracis strain lacking the HtrC protease did not generate the same stable YpeB
      products. In B. anthracis and Bacillus subtilis htrC mutants, YpeB was partially
      stabilized during germination but was still degraded at a reduced rate by other,
      unidentified proteases. Purified HtrC cleaved YpeB to a fragment similar to that
      observed in vivo, and this cleavage was stimulated by Mn(2+) or Ca(2+) ions. A
      lack of HtrC did not stabilize YpeB or SleB during spore formation in the absence
      of the partner protein, indicating other proteases are involved in their
      degradation during sporulation. 

PMID- 25384477
TI  - Pseudomonas aeruginosa LysR PA4203 regulator NmoR acts as a repressor of the
      PA4202 nmoA gene, encoding a nitronate monooxygenase.
AB  - The PA4203 gene encodes a LysR regulator and lies between the ppgL gene (PA4204),
      which encodes a periplasmic gluconolactonase, and, in the opposite orientation,
      the PA4202 (nmoA) gene, coding for a nitronate monooxygenase, and ddlA (PA4201),
      encoding a d-alanine alanine ligase. The intergenic regions between PA4203 and
      ppgL and between PA4203 and nmoA are very short (79 and 107 nucleotides,
      respectively). Here we show that PA4203 (nmoR) represses its own transcription
      and the expression of nmoA. A chromatin immunoprecipitation analysis showed the
      presence of a single NmoR binding site between nmoA and nmoR, which was confirmed
      by electrophoretic mobility shift assays (EMSAs) with the purified NmoR protein.
      Despite this observation, a transcriptome analysis revealed more genes to be
      affected in an nmoR mutant, including genes known to be part of the MexT LysR
      activator regulon. The PA1225 gene, encoding a quinone oxidoreductase, was the
      most highly upregulated gene in the nmoR deletion mutant, independently of MexT.
      Finally, deletion of the nmoA gene resulted in an increased sensitivity of the
      cells to 3-nitropropionic acid (3-NPA), confirming the role of the nitronate
      monooxygenase protein in the detoxification of nitronate. 

PMID- 25384478
TI  - The putative eukaryote-like O-GlcNAc transferase of the cyanobacterium
      Synechococcus elongatus PCC 7942 hydrolyzes UDP-GlcNAc and is involved in
      multiple cellular processes.
AB  - The posttranslational addition of a single O-linked beta-N-acetylglucosamine (O
      GlcNAc) to serine or threonine residues regulates numerous metazoan cellular
      processes. The enzyme responsible for this modification, O-GlcNAc transferase
      (OGT), is conserved among a wide variety of organisms and is critical for the
      viability of many eukaryotes. Although OGTs with domain structures similar to
      those of eukaryotic OGTs are predicted for many bacterial species, the cellular
      roles of these OGTs are unknown. We have identified a putative OGT in the
      cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology
      and similar domain structure to eukaryotic OGTs. An OGT deletion mutant was
      created and found to exhibit several phenotypes. Without agitation, mutant cells
      aggregate and settle out of the medium. The mutant cells have higher free
      inorganic phosphate levels, wider thylakoid lumen, and differential accumulation
      of electron-dense inclusion bodies. These phenotypes are rescued by
      reintroduction of the wild-type OGT but are not fully rescued by OGTs with single
      amino acid substitutions corresponding to mutations that reduce eukaryotic OGT
      activity. S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar
      donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion
      mutant phenotypes had reduced or no activity. These results suggest that
      bacterial eukaryote-like OGTs, like their eukaryotic counterparts, influence
      multiple processes. 

PMID- 25384479
TI  - The trpE gene negatively regulates differentiation of heterocysts at the level of
      induction in Anabaena sp. strain PCC 7120.
AB  - Levels of 2-oxoglutarate (2-OG) reflect nitrogen status in many bacteria. In
      heterocystous cyanobacteria, a spike in the 2-OG level occurs shortly after the
      removal of combined nitrogen from cultures and is an integral part of the
      induction of heterocyst differentiation. In this work, deletion of one of the two
      annotated trpE genes in Anabaena sp. strain PCC 7120 resulted in a spike in the 2
      OG level and subsequent differentiation of a wild-type pattern of heterocysts
      when filaments of the mutant were transferred from growth on ammonia to growth on
      nitrate. In contrast, 2-OG levels were unaffected in the wild type, which did not
      differentiate under the same conditions. An inverted-repeat sequence located
      upstream of trpE bound a central regulator of differentiation, HetR, in vitro and
      was necessary for HetR-dependent transcription of a reporter fusion and
      complementation of the mutant phenotype in vivo. Functional complementation of
      the mutant phenotype with the addition of tryptophan suggested that levels of
      tryptophan, rather than the demonstrated anthranilate synthase activity of TrpE,
      mediated the developmental response of the wild type to nitrate. A model is
      presented for the observed increase in 2-OG in the trpE mutant. 

PMID- 25384480
TI  - LytR-CpsA-Psr enzymes as determinants of Bacillus anthracis secondary cell wall
      polysaccharide assembly.
AB  - Bacillus anthracis, the causative agent of anthrax, replicates as chains of
      vegetative cells by regulating the separation of septal peptidoglycan. Surface
      (S)-layer proteins and associated proteins (BSLs) function as chain length
      determinants and bind to the secondary cell wall polysaccharide (SCWP). In this
      study, we identified the B. anthracis lcpD mutant, which displays increased chain
      length and S-layer assembly defects due to diminished SCWP attachment to
      peptidoglycan. In contrast, the B. anthracis lcpB3 variant displayed reduced cell
      size and chain length, which could be attributed to increased deposition of BSLs.
      In other bacteria, LytR-CpsA-Psr (LCP) proteins attach wall teichoic acid (WTA)
      and polysaccharide capsule to peptidoglycan. B. anthracis does not synthesize
      these polymers, yet its genome encodes six LCP homologues, which, when expressed
      in S. aureus, promote WTA attachment. We propose a model whereby B. anthracis
      LCPs promote attachment of SCWP precursors to discrete locations in the
      peptidoglycan, enabling BSL assembly and regulated separation of septal
      peptidoglycan. 

PMID- 25384481
TI  - The EcoKI type I restriction-modification system in Escherichia coli affects but
      is not an absolute barrier for conjugation.
AB  - The rapid evolution of bacteria is crucial to their survival and is caused by
      exchange, transfer, and uptake of DNA, among other things. Conjugation is one of
      the main mechanisms by which bacteria share their DNA, and it is thought to be
      controlled by varied bacterial immune systems. Contradictory results about
      restriction-modification systems based on phenotypic studies have been presented
      as reasons for a barrier to conjugation with and other means of uptake of
      exogenous DNA. In this study, we show that inactivation of the R.EcoKI
      restriction enzyme in strain Escherichia coli K-12 strain MG1655 increases the
      conjugational transfer of plasmid pOLA52, which carriers two EcoKI recognition
      sites. Interestingly, the results were not absolute, and uptake of unmethylated
      pOLA52 was still observed in the wild-type strain (with an intact hsdR gene) but
      at a reduction of 85% compared to the uptake of the mutant recipient with a
      disrupted hsdR gene. This leads to the conclusion that EcoKI restriction
      modification affects the uptake of DNA by conjugation but is not a major barrier
      to plasmid transfer. 

PMID- 25384482
TI  - Proline metabolism increases katG expression and oxidative stress resistance in
      Escherichia coli.
AB  - The oxidation of l-proline to glutamate in Gram-negative bacteria is catalyzed by
      the proline utilization A (PutA) flavoenzyme, which contains proline
      dehydrogenase (PRODH) and Delta(1)-pyrroline-5-carboxylate (P5C) dehydrogenase
      domains in a single polypeptide. Previous studies have suggested that aside from
      providing energy, proline metabolism influences oxidative stress resistance in
      different organisms. To explore this potential role and the mechanism, we
      characterized the oxidative stress resistance of wild-type and putA mutant
      strains of Escherichia coli. Initial stress assays revealed that the putA mutant
      strain was significantly more sensitive to oxidative stress than the parental
      wild-type strain. Expression of PutA in the putA mutant strain restored oxidative
      stress resistance, confirming that depletion of PutA was responsible for the
      oxidative stress phenotype. Treatment of wild-type cells with proline
      significantly increased hydroperoxidase I (encoded by katG) expression and
      activity. Furthermore, the DeltakatG strain failed to respond to proline,
      indicating a critical role for hydroperoxidase I in the mechanism of proline
      protection. The global regulator OxyR activates the expression of katG along with
      several other genes involved in oxidative stress defense. In addition to katG,
      proline increased the expression of grxA (glutaredoxin 1) and trxC (thioredoxin
      2) of the OxyR regulon, implicating OxyR in proline protection. Proline oxidative
      metabolism was shown to generate hydrogen peroxide, indicating that proline
      increases oxidative stress tolerance in E. coli via a preadaptive effect
      involving endogenous hydrogen peroxide production and enhanced catalase
      peroxidase activity. 

PMID- 25384483
TI  - Nonacetogenic growth of the acetogen Acetobacterium woodii on 1,2-propanediol.
AB  - Acetogenic bacteria can grow by the oxidation of various substrates coupled to
      the reduction of CO2 in the Wood-Ljungdahl pathway. Here, we show that growth of
      the acetogen Acetobacterium woodii on 1,2-propanediol (1,2-PD) as the sole carbon
      and energy source is independent of acetogenesis. Enzymatic measurements and
      metabolite analysis revealed that 1,2-PD is dehydrated to propionaldehyde, which
      is further oxidized to propionyl coenzyme A (propionyl-CoA) with concomitant
      reduction of NAD. NADH is reoxidized by reducing propionaldehyde to propanol. The
      potential gene cluster coding for the responsible enzymes includes genes coding
      for shell proteins of bacterial microcompartments. Electron microscopy revealed
      the presence of microcompartments as well as storage granules in cells grown on
      1,2-PD. Gene clusters coding for the 1,2-PD pathway can be found in other
      acetogens as well, but the distribution shows no relation to the phylogeny of the
      organisms. 

PMID- 25384484
TI  - Lactococcus lactis metabolism and gene expression during growth on plant tissues.
AB  - Lactic acid bacteria have been isolated from living, harvested, and fermented
      plant materials; however, the adaptations these bacteria possess for growth on
      plant tissues are largely unknown. In this study, we investigated plant habitat
      specific traits of Lactococcus lactis during growth in an Arabidopsis thaliana
      leaf tissue lysate (ATL). L. lactis KF147, a strain originally isolated from
      plants, exhibited a higher growth rate and reached 7.9-fold-greater cell
      densities during growth in ATL than the dairy-associated strain L. lactis IL1403.
      Transcriptome profiling (RNA-seq) of KF147 identified 853 induced and 264
      repressed genes during growth in ATL compared to that in GM17 laboratory culture
      medium. Genes induced in ATL included those involved in the arginine deiminase
      pathway and a total of 140 carbohydrate transport and metabolism genes, many of
      which are involved in xylose, arabinose, cellobiose, and hemicellulose
      metabolism. The induction of those genes corresponded with L. lactis KF147
      nutrient consumption and production of metabolic end products in ATL as measured
      by gas chromatography-time of flight mass spectrometry (GC-TOF/MS) untargeted
      metabolomic profiling. To assess the importance of specific plant-inducible genes
      for L. lactis growth in ATL, xylose metabolism was targeted for gene knockout
      mutagenesis. Wild-type L. lactis strain KF147 but not an xylA deletion mutant was
      able to grow using xylose as the sole carbon source. However, both strains grew
      to similarly high levels in ATL, indicating redundancy in L. lactis carbohydrate
      metabolism on plant tissues. These findings show that certain strains of L.
      lactis are well adapted for growth on plants and possess specific traits relevant
      for plant-based food, fuel, and feed fermentations. 

PMID- 25384485
TI  - Kawasaki shock syndrome complicating a recurrence of Kawasaki disease.
AB  - We describe a case of recurrent Kawasaki disease (KD) in a non-Asian 6-year-old
      boy who had been diagnosed with typical KD without cardiac involvement at age 3
      years. He was admitted to the PICU 3 years later for heart failure, hypotension,
      and deterioration of his general condition. Ultrasonography revealed left
      ventricular dysfunction with a 44% ejection fraction and grade I mitral valve
      failure without coronary artery involvement. Subsequent observation of hyperemic
      conjunctiva, bilateral cervical adenopathies with erythematous skin (normal neck
      ultrasound and computed axial tomography findings), peeling of the fingertips at
      day 8 of the illness, and occurrence of an inflammatory syndrome led to a
      diagnosis of incomplete recurrent KD with a clinical picture of Kawasaki shock
      syndrome (KSS). Clinical improvement was rapidly obtained after intravenous
      immunoglobulin and intravenous corticosteroid therapy (30 mg/kg per day for 3
      subsequent days). Left ventricular function gradually improved, with ultrasound
      returning to normal after 3 months. Diagnosis was difficult to establish because
      of the recurrence of the disease and the incomplete clinical picture, with
      clinical features of KSS. Physicians need to be aware of these pitfalls in the
      management of patients with clinical signs of KD. 

PMID- 25384486
TI  - Sinusitis and pneumonia hospitalization after introduction of pneumococcal
      conjugate vaccine.
AB  - BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae is a major cause of pneumonia
      and sinusitis. Pneumonia kills >1 million children annually, and sinusitis is a
      potentially serious pediatric disease that increases the risk of orbital and
      intracranial complications. Although pneumococcal conjugate vaccine (PCV) is
      effective against invasive pneumococcal disease, its effectiveness against
      pneumonia is less consistent, and its effect on sinusitis is not known. We
      compared hospitalization rates due to sinusitis, pneumonia, and empyema before
      and after sequential introduction of PCV7 and PCV13. METHOD: All children 0 to
      <18 years old hospitalized for sinusitis, pneumonia, or empyema in Stockholm
      County, Sweden, from 2003 to 2012 were included in a population-based study of
      hospital registry data on hospitalizations due to sinusitis, pneumonia, or
      empyema. Trend analysis, incidence rates, and rate ratios (RRs) were calculated
      comparing July 2003 to June 2007 with July 2008 to June 2012, excluding the year
      of PCV7 introduction. RESULTS: Hospitalizations for sinusitis decreased
      significantly in children aged 0 to <2 years, from 70 to 24 cases per 100 000
      population (RR = 0.34, P < .001). Hospitalizations for pneumonia decreased
      significantly in children aged 0 to <2 years, from 450 to 366 per 100 000
      population (RR = 0.81, P < .001) and in those aged 2 to <5 years from 250 to 212
      per 100 000 population (RR = 0.85, P = .002). Hospitalization for empyema
      increased nonsignificantly. Trend analyses showed increasing hospitalization for
      pneumonia in children 0 to <2 years before intervention and confirmed a decrease
      in hospitalizations for sinusitis and pneumonia in children aged 0 to <5 years
      after intervention. CONCLUSIONS: PCV7 and PCV13 vaccination led to a 66% lower
      risk of hospitalization for sinusitis and 19% lower risk of hospitalization for
      pneumonia in children aged 0 to <2 years, in a comparison of 4 years before and 4
      years after vaccine introduction.

PMID- 25384487
TI  - Anti-DFS70 antibodies: a useful biomarker in a pediatric case with suspected
      autoimmune disease.
AB  - Antidense fine speckles 70 (anti-DFS70) antibodies, a peculiar antinuclear
      antibody (ANA) pattern by indirect immunofluorescence, is frequently observed in
      ANA-positive individuals with no evidence of systemic autoimmune rheumatic
      disease. They may be found in many different inflammatory conditions and in
      healthy individuals. We herein report a case of an 8-year-old girl presenting
      with generalized edema, hypertension, hepatomegaly, and a history of pharyngitis,
      which occurred 3 weeks earlier. Laboratory analysis revealed low complement C3 (6
      mg/dL), microhematuria, and proteinuria. A diagnosis of acute glomerulonephritis
      was made. Anti-dsDNA, antiextractable nuclear antigens, and antineutrophil
      cytoplasmic antibodies were negative. However, a highly positive (1:640) ANA
      immunofluorescence test with dense fine speckles pattern was found. The presence
      of anti-DFS70 immunoglobulin G antibodies was confirmed by a specific
      immunoassay. In conclusion, the presence of isolated anti-DFS70 antibodies may be
      useful to exclude an autoimmune pathogenesis in those children with a positive
      ANA test and a clinical picture possibly attributable to systemic autoimmune
      rheumatic disease. This will avoid further unnecessary investigation with the
      potential for incorrect diagnosis and possibly harmful treatment. 

PMID- 25384488
TI  - Evacuation of a neonatal intensive care unit in a disaster: lessons from
      Hurricane Sandy.
AB  - NICU patients are among those potentially most vulnerable to the effects of
      natural or man-made disaster on a medical center. The published data on
      evacuations of NICU patients in the setting of disaster are sparse. In October of
      2012, New York University Langone Medical Center was evacuated during Hurricane
      Sandy in the setting of a power outage secondary to a coastal surge. In this
      setting, 21 neonates were safely evacuated from the medical center's NICU to
      receiving hospitals within New York City in a span of 4.5 hours. Using data
      recorded during the evacuation and from staff debriefings, we describe the
      challenges faced and lessons learned during both the power outage and vertical
      evacuation. From our experience, we identify several elements that are important
      to the functioning of an NICU in a disaster or to an evacuation that may be
      incorporated into future NICU-focused disaster planning. These include a clear
      command structure, backups (personnel, communication, medical information, and
      equipment), establishing situational awareness, regional coordination, and
      flexibility as well as special attention to families and to the availability of
      neonatal transport resources. 

PMID- 25384489
TI  - Pediatric exposure to laundry detergent pods.
AB  - OBJECTIVE: Laundry detergent pods are a new product in the US marketplace. This
      study investigates the epidemiologic characteristics and outcomes of laundry
      detergent pod exposures among young children in the United States. METHODS: Using
      data from the National Poison Data System, exposures to laundry detergent pods
      among children younger than 6 years of age during 2012-2013 were investigated.
      RESULTS: There were 17 230 children younger than 6 years exposed to laundry
      detergent pods in 2012-2013. From March 2012 to April 2013, the monthly number of
      exposures increased by 645.3%, followed by a 25.1% decrease from April to
      December 2013. Children younger than 3 years accounted for 73.5% of cases. The
      major route of exposure was ingestion, accounting for 79.7% of cases. Among
      exposed children, 4.4% were hospitalized and 7.5% experienced a moderate or major
      medical outcome. A spectrum of clinical effects from minor to serious was seen
      with ingestion and ocular exposures. There were 102 patients (0.6%) exposed to a
      detergent pod via ingestion, aspiration, or a combination of routes, including
      ingestion, who required tracheal intubation. There was 1 confirmed death.
      CONCLUSIONS: Laundry detergent pods pose a serious poisoning risk to young
      children. This nationwide study underscores the need for increased efforts to
      prevent exposure of young children to these products, which may include
      improvements in product packaging and labeling, development of a voluntary
      product safety standard, and public education. Product constituent reformulation
      is another potential strategy to mitigate the severity of clinical effects of
      laundry detergent pod exposure.

PMID- 25384490
TI  - Adolescent vaccine co-administration and coverage in New York City: 2007-2013.
AB  - OBJECTIVES: To investigate adolescent vaccination in New York City, we assessed
      tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal conjugate
      (MCV4), and human papillomavirus (HPV) vaccine uptake, vaccine co-administration,
      and catch-up coverage over time. METHODS: We analyzed data from the Citywide
      Immunization Registry, a population-based immunization information system, to
      measure vaccine uptake and co-administration, defined as a Tdap vaccination visit
      where MCV4 or HPV vaccine was co-administered, among 11-year-olds. Catch-up
      vaccinations were evaluated through 2013 for adolescents born 1996 to 2000, by
      birth cohort. HPV vaccination among boys included data from 2010 to 2013.
      RESULTS: Adolescent vaccine administration was greatest during the back-to-school
      months of August to October and was highest for Tdap. Although MCV4 uptake
      improved over the study years, HPV vaccine uptake among girls stagnated; boys
      achieved similar uptake of HPV vaccine by 2012. By 2013, 65.4% had MCV4 co
      administered with Tdap vaccine, whereas 28.4% of girls and 25.9% of boys had
      their first dose of HPV vaccine co-administered. By age 17, Tdap and MCV4
      vaccination coverage increased to 97.5% and 92.8%, respectively, whereas >=1-dose
      and 3-dose HPV vaccination coverage were, respectively, 77.5% and 53.1% for girls
      and 49.3% and 21.6% for boys. Age-specific vaccination coverage increased with
      each successive birth cohort (P < .001). CONCLUSIONS: From 2007 to 2013, there
      were greater improvements in Tdap and MCV4 vaccination than HPV vaccination, for
      which co-administration with Tdap vaccine and coverage through adolescence
      remained lower. Parent and provider outreach efforts should promote timely HPV
      vaccination for all adolescents and vaccine co-administration.

PMID- 25384492
TI  - Preventing hospitalizations in children with medical complexity: a systematic
      review.
AB  - BACKGROUND AND OBJECTIVES: Children with medical complexity (CMC) account for
      disproportionately high hospital use, and it is unknown if hospitalizations may
      be prevented. Our objective was to summarize evidence from (1) studies
      characterizing potentially preventable hospitalizations in CMC and (2)
      interventions aiming to reduce such hospitalizations. METHODS: Our data sources
      include Medline, Cochrane Central Register of Controlled Trials, Web of Science,
      and Cumulative Index to Nursing and Allied Health Literature databases from their
      originations, and hand search of article bibliographies. Observational studies (n
      = 13) characterized potentially preventable hospitalizations, and experimental
      studies (n = 4) evaluated the efficacy of interventions to reduce them. Data were
      extracted on patient and family characteristics, medical complexity and
      preventable hospitalization indicators, hospitalization rates, costs, and days.
      Results of interventions were summarized by their effect on changes in hospital
      use. RESULTS: Preventable hospitalizations were measured in 3 ways: ambulatory
      care sensitive conditions, readmissions, or investigator-defined criteria.
      Postsurgical patients, those with neurologic disorders, and those with medical
      devices had higher preventable hospitalization rates, as did those with public
      insurance and nonwhite race/ethnicity. Passive smoke exposure, nonadherence to
      medications, and lack of follow-up after discharge were additional risks.
      Hospitalizations for ambulatory care sensitive conditions were less common in
      more complex patients. Patients receiving home visits, care coordination, chronic
      care-management, and continuity across settings had fewer preventable
      hospitalizations. CONCLUSIONS: There were a limited number of published studies.
      Measures for CMC and preventable hospitalizations were heterogeneous. Risk of
      bias was moderate due primarily to limited controlled experimental designs.
      Reductions in hospital use among CMC might be possible. Strategies should target
      primary drivers of preventable hospitalizations.

PMID- 25384491
TI  - Regulations to promote healthy sleep practices in child care.
AB  - OBJECTIVES: The purpose of this study was to assess state licensing and
      administrative regulations promoting healthy sleep practices in child care and to
      compare these regulations to national recommendations. METHODS: We reviewed
      regulations related to healthy sleep practices for all states and territories for
      both child care centers (centers) and family child care homes (homes). We
      compared regulations with Institute of Medicine recommendations to promote sleep
      in child care, including (1) create environments that ensure restful sleep; (2)
      encourage sleep-promoting behaviors and practices; (3) encourage practices that
      promote child self-regulation of sleep; and (4) seek consultation yearly from a
      sleep expert. We used Cochran-Mantel-Haenszel trend tests to assess associations
      between geographic region and number of regulations consistent with the
      recommendations. RESULTS: The mean number of regulations for states was 0.9 for
      centers and 0.8 for homes out of a possible 4.0. For centers, no state had
      regulations for all 4 recommendations; 11 states had regulations for 2 of the 4
      recommendations. For homes, 9 states had regulations for 2 of the
      recommendations. States in the Northeast had the greatest mean number of
      regulations for centers (1.2) and homes (1.1), and states in the South had the
      fewest (0.7 and 0.7, respectively); these geographic differences were significant
      for centers (P = .03) but not homes (P = .14). CONCLUSIONS: More states in the
      Northeast had regulations consistent with the Institute of Medicine sleep
      recommendations, but overall few states had regulations consistent with the
      recommendations.

PMID- 25384493
TI  - A team-based approach to reducing cardiac monitor alarms.
AB  - BACKGROUND AND OBJECTIVES: Excessive cardiac monitor alarms lead to
      desensitization and alarm fatigue. We created and implemented a standardized
      cardiac monitor care process (CMCP) on a 24-bed pediatric bone marrow transplant
      unit. The aim of this project was to decrease monitor alarms through the use of
      team-based standardized care and processes. METHODS: Using small tests of change,
      we developed and implemented a standardized CMCP that included: (1) a process for
      initial ordering of monitor parameters based on age-appropriate standards; (2)
      pain-free daily replacement of electrodes; (3) daily individualized assessment of
      cardiac monitor parameters; and (4) a reliable method for appropriate
      discontinuation of monitor. The Model for Improvement was used to design, test,
      and implement changes. The changes that were implemented after testing and
      adaptation were: family/patient engagement in the CMCP; creation of a monitor
      care log to address parameters, lead changes, and discontinuation; development of
      a pain-free process for electrode removal; and customized monitor delay and
      customized threshold parameters. RESULTS: From January to November 2013, percent
      compliance with each of the 4 components of the CMCP increased. Overall
      compliance with the CMCP increased from a median of 38% to 95%. During this time,
      the median number of alarms per patient-day decreased from 180 to 40.
      CONCLUSIONS: Implementation of the standardized CMCP resulted in a significant
      decrease in cardiac monitor alarms per patient day. We recommend a team-based
      approach to monitor care, including individualized assessment of monitor
      parameters, daily lead change, and proper discontinuation of the monitors.

PMID- 25384494
TI  - Changes in obesity between fifth and tenth grades: a longitudinal study in three
      metropolitan areas.
AB  - BACKGROUND: Despite epidemic childhood obesity levels, we know little about how
      BMI changes from preadolescence to adolescence and what factors influence
      changes. METHODS: We studied 3961 randomly selected public school students and 1
      parent per student in 3 US metropolitan areas in fifth and again in tenth grades.
      In each grade, we measured child and parent height/weight and calculated BMI
      category. We examined whether baseline sociodemographic characteristics, child
      health-related factors, and parental obesity were significantly associated with
      exit from and entry into obesity from fifth to tenth grade. RESULTS: Fifth- and
      tenth-graders were 1%/2% underweight, 53%/60% normal weight, 19%/18% overweight,
      and 26%/20% obese, respectively. Among obese tenth-graders, 83% had been obese as
      fifth-graders and 13% had been overweight. Sixty-five percent of obese fifth
      graders remained obese as tenth-graders, and 23% transitioned to overweight.
      Multivariately, obese fifth-graders who perceived themselves to be much heavier
      than ideal (P = .01) and those who had lower household education (P = .006) were
      less likely to exit obesity; by contrast, overweight fifth-graders were more
      likely to become obese if they had an obese parent (P < .001) or watched more
      television (P = .02). CONCLUSIONS: Obese fifth-graders face challenges in
      reducing obesity, especially when they lack advantages associated with higher
      socioeconomic status or when they have a negative body image. Clinicians and
      others should educate parents on the importance of preventing obesity very early
      in development. Children who are not yet obese by fifth grade but who have an
      obese parent or who watch considerable television might benefit from monitoring,
      as might children who have negative body images.

PMID- 25384495
TI  - Chinese pediatricians face a crisis: should they stay or leave?

PMID- 25384496
TI  - Changes in child mortality over time across the wealth gradient in less-developed
      countries.
AB  - BACKGROUND: It is unknown whether inequalities in under-5 mortality by wealth in
      low- and middle-income countries (LMICs) are growing or declining. METHODS: All
      Demographic and Health Surveys conducted between 2002 and 2012 were used to
      measure under-5 mortality trends in 3 wealth tertiles. Two approaches were used
      to estimate changes in under-5 mortality: within-survey changes from all 54
      countries, and between-survey changes for 29 countries with repeated survey
      waves. The principal outcome measures include annual decline in mortality, and
      the ratio of mortality between the poorest and least-poor wealth tertiles.
      RESULTS: Mortality information in 85 surveys from 929 224 households and 1 267
      167 women living in 54 countries was used. In the subset of 29 countries with
      repeat surveys, mortality declined annually by 4.36, 3.36, and 2.06 deaths per
      1000 live births among the poorest, middle, and least-poor tertiles, respectively
      (P = .031 for difference). The mortality ratio declined from 1.68 to 1.48 during
      the study period (P = .006 for trend). In the complete set of 85 surveys, the
      mortality ratio declined in 64 surveys (from 2.11 to 1.55), and increased in 21
      surveys (from 1.58 to 1.88). Multivariate analyses suggest that convergence was
      associated with good governance (P <= .03 for 4 governance indicators: government
      effectiveness, rule of law, regulatory quality, and control of corruption).
      CONCLUSIONS: Overall, under-5 mortality in low- and middle-income countries has
      decreased faster among the poorest compared with the least poor between 1995 and
      2012, but progress in some countries has lagged, especially with poor governance.

PMID- 25384497
TI  - Downregulation of gangliotetraosylceramide and beta1,3-galactosyltransferase-4
      gene expression by Smads during transforming growth factor beta-induced
      epithelial-mesenchymal transition.
AB  - The process of epithelial-mesenchymal transition (EMT) is essential for the
      proliferation and metastasis of tumor cells. Our previous study demonstrated that
      the expression of gangliotetraosylceramide (Gg4) and the transcription of UDP
      Gal: beta1,3-galactosyltransferase-4 (beta3GalT4), a gene which controls the
      expression of Gg4, are reduced during transforming growth factor (TGF)-beta
      induced EMT in normal murine mammary gland (NMuMG) cells. The present study
      revealed that the transcription level of beta3GalT4 in patients with breast
      cancer was decreased compared with healthy control subjects. However, the
      molecular basis underlying these effects remains to be elucidated. Analysis of
      the beta3GalT4 promoter sequence revealed a putative Smad-binding element (SBE)
      of Smad4, which is a transcriptional factor in TGFbeta responses and forms a
      complex with Smad3. To clarify the association between the Smad3/4 complex and
      the beta3GalT4 gene during EMT in NMuMG cells, an electrophoretic mobility shift
      assay and a chromatin immunoprecipitation assay were performed. The Smad3/4
      complex was found to bind directly to the SBE of the beta3GalT4 promoter.
      Overexpression of Smad3 and Smad4 through stable transfection had no notable
      effect on cell phenotype, but did alter the expression of various EMT protein
      markers. Treatment with TGFbeta reduced the expression of Gg4 and the mRNA levels
      of the beta3GalT4 gene in Smad3- and Smad4-overexpressing cells compared with
      vector-transfected cells. Expression of the epithelial markers E-cadherin and
      beta-catenin decreased in parallel with the reduction in Gg4. These findings
      suggested that the activated Smad3/4 complex downregulated the expression of Gg4
      and the beta3GalT4 gene through translocation into the nucleus and binding to the
      beta3GalT4 promoter.

PMID- 25384498
TI  - Sulindac attenuates valproic acid-induced oxidative stress levels in primary
      cultured cortical neurons and ameliorates repetitive/stereotypic-like movement
      disorders in Wistar rats prenatally exposed to valproic acid.
AB  - Accumulating evidence suggests that anti-inflammatory agents and antioxidants
      have neuroprotective properties and may be beneficial in the treatment of
      neurodevelopental disorders, such as autism. In the present study, the possible
      neuroprotective properties of sulindac, a non-steroidal anti-inflammatory drug
      (NSAID), were investigated in vitro using cultured cortical neurons with valproic
      acid (VPA)-induced neurotoxicity, as well as in vivo through the behavioral
      analysis of rats prenatally exposed to VPA as a model of autism. VPA induced 4
      hydroxynonenal (4-HNE) expression, reactive oxygen species (ROS) generation and
      decreased cell viability in primary cultured cortical neurons established from
      timed-pregnant (embryonic day 18) Wistar rat pups. However, co-incubation of the
      neurons with VPA and sulindac reduced oxidative stress and increased cell
      viability. The rats were administered an intraperitoneal injection with one of
      the following: VPA, sulindac, VPA and sulindac, or physiological saline, and
      their offspring were subjected to the open field test. During the test trials,
      repetitive/stereotypic-like movements for each rat were recorded and analyzed.
      The results revealed that treatment with both sulindac and VPA reduced the VPA
      induced repetitive/stereotypic-like activity and the sulindac and VPA-treated
      animals responded better in the open field test compared to the VPA-treated
      animals. The results from the present study demonstrate that the antioxidant
      properties of sulindac may prove to be beneficial in the treatment of autism,
      suggesting that the upregulation of the Wnt/beta-catenin signaling pathway
      disrupts oxidative homeostasis and facilitates susceptibility to autism.

PMID- 25384499
TI  - Chidamide, a histone deacetylase inhibitor, functions as a tumor inhibitor by
      modulating the ratio of Bax/Bcl-2 and P21 in pancreatic cancer.
AB  - Chidamide is a newly designed histone deacetylase (HDAC) inhibitor that has been
      applied in clinical trials. This study aimed to test the effect of Chidamide on
      proliferation and apoptosis in pancreatic cancer cell lines and in vivo tumors,
      as well as to determine the underlying mechanism. The PaTu8988 pancreatic tumor
      cell line either in culture or inoculated in nude mice were used to evaluate the
      antitumor characteristics of Chidamide. Proliferation and apoptosis of cultured
      PaTu8988 cells were examined by CCK-8 assay and Annexin V-FITC/PI double staining
      assay, respectively. Alterations in protein expression, including Caspase-3, Bcl
      2-like protein 4 (Bax), B-cell lymphoma 2 (Bcl-2) and p21, were tested by western
      blot analysis. The mRNA of different HDACs was examined by quantitative
      polymerase chain reaction (qPCR) experiments. Chidamide suppressed cell
      proliferation and induced early apoptosis of pancreatic tumor cells in a dose
      dependent manner after 48 h of treatment. Similarly, the in vivo study using
      pancreatic tumor murine model showed that Chidamide administration significantly
      inhibited the growth of pancreatic tumor and induced tumor cell apoptosis. The in
      vitro and in vivo studies found that Chidamide treatment significantly decreased
      the expression of type I HDACs, uncleaved Caspase-3 and p21 and increased the
      ratio of Bax/Bcl-2 expression. The results from the in vitro and in vivo studies
      suggested Chidamide might suppress the proliferation of pancreatic tumor cells by
      downregulating the expression of type I HDACs and p21, and promoting
      mitochondrial apoptosis pathway-dependent cell apoptosis in a dose-dependent
      manner. The study provided more evidence for clinical administration of Chidamide
      that targets pancreatic tumor cells and identified potential molecular targets
      for the development of potent anticancer drugs.

PMID- 25384500
TI  - Spontaneous graphitization of ultrathin cubic structures: a computational study.
AB  - Results based on ab initio density functional calculations indicate that cubic
      diamond, boron nitride, and many other cubic structures including rocksalt share
      a general graphitization tendency in ultrathin films terminated by close-packed
      (111) surfaces. Whereas such compounds often show an energy preference for cubic
      rather than layered atomic arrangements in the bulk, the surface energy of
      layered systems is commonly lower than that of their cubic counterparts. We
      determine the critical slab thickness for a range of systems, below which a
      spontaneous conversion from a cubic to a layered graphitic structure occurs,
      driven by surface energy reduction in surface-dominated structures. 

PMID- 25384501
TI  - US Supreme Court will hear challenge to Obamacare subsidies.

PMID- 25384502
TI  - Outcome After Surgical Repair of Proximal Hamstring Avulsions: A Systematic
      Review.
AB  - BACKGROUND: At the present time, no systematic review, including a quality
      assessment, has been published about the outcome after proximal hamstring
      avulsion repair. PURPOSE: To determine the outcome after surgical repair of
      proximal hamstring avulsions, to compare the outcome after acute (<=4 weeks) and
      delayed repairs (>4 weeks), and to compare the outcome after different surgical
      techniques. STUDY DESIGN: Systematic review and best-evidence synthesis. METHODS:
      PubMed, CINAHL, SPORTdiscus, Cochrane library, EMBASE, and Web of Science were
      searched (up to December 2013) for eligible studies. Two authors screened the
      search results separately, while quality assessment was performed by 2 authors
      independently using the Physiotherapy Evidence Database (PEDro) scale. A best
      evidence synthesis was subsequently used. RESULTS: Thirteen studies (387
      participants) were included in this review. There were no studies with control
      groups of nonoperatively treated proximal hamstring avulsions. All studies had a
      low methodological quality. After surgical repair of proximal hamstring avulsion,
      76% to 100% returned to sports, 55% to 100% returned to preinjury activity level,
      and 88% to 100% were satisfied with surgery. Mean hamstring strength varied
      between reporting studies (78%-101%), and hamstring endurance and flexibility
      were fully restored compared with the unaffected side. Symptoms of residual pain
      were reported by 8% to 61%, and reported risk of major complications was low (3%
      rerupture rate). No to minimal difference in outcome was found between acute and
      delayed repair in terms of return to sports, patient satisfaction, hamstring
      strength, and pain. Achilles allograft reconstruction and primary repair with
      suture anchors led to comparable results. CONCLUSION: The quality of studies
      included is low. Surgical repair of proximal hamstring avulsions appears to
      result in a subjective highly satisfying outcome. However, decreased strength,
      residual pain, and decreased activity level were reported by a relevant number of
      patients. Minimal to no differences in outcome of acute and delayed repairs were
      found. Limited evidence suggests that an Achilles allograft reconstruction yields
      results comparable with primary repair in delayed cases where primary repair is
      not possible. High-level studies are required to confirm these findings.

PMID- 25384503
TI  - Long-term clinical and radiographic results after delayed anterior cruciate
      ligament reconstruction in adolescents.
AB  - BACKGROUND: The risk of further intra-articular damage associated with
      nonoperative or delayed anterior cruciate ligament (ACL) reconstruction must be
      considered against the risk of growth disturbance with early reconstruction and
      transphyseal drilling. Long-term follow-ups after the surgical treatment of ACL
      injuries in adolescents are rare. PURPOSE: To evaluate results 10 to 20 years
      after ACL reconstruction in terms of the radiographic presence of osteoarthritis,
      clinical assessments, and health-related quality of life in patients who were
      adolescents at the time of surgery. STUDY DESIGN: Case series; Level of evidence,
      4. METHODS: Thirty-two adolescents (mean age, 15.2 years [range, 12-16 years]; 11
      boys, 21 girls), with a symptomatic unilateral ACL rupture, underwent
      reconstruction using bone-patellar tendon-bone (n=10) or hamstring tendon (n=22)
      autografts at an almost skeletally mature age according to Tanner stage 4. Twenty
      nine patients (91%) underwent clinical, radiographic, and health-related quality
      of life assessments after 10 to 20 years (mean, 175 months). RESULTS: The mean
      time between the injury and index surgery was 11.6 months. The reconstructed knee
      had significantly more osteoarthritic changes compared with the noninvolved
      contralateral knee (P=.001). Preoperatively, the median Tegner activity level was
      4 (range, 2-8), and the median Lysholm knee score was 75 (range, 50-90) points.
      At follow-up, the respective median values were 4 (range, 1-7) and 84 (range, 34
      100) points (P=not significant [preoperatively vs follow-up]). The median finding
      for the single-legged hop test was 84% (range, 0%-105%) preoperatively and 93%
      (range, 53%-126%) at follow-up (P=.01). At follow-up, muscle strength
      measurements displayed more than 90% of the noninvolved leg in both extension and
      flexion. The manual Lachman test result was significantly improved at follow-up
      compared with preoperatively (P<.001). The 36-item Short Form Health Survey (SF
      36) revealed scores comparable with those of healthy controls. The mean EuroQol
      (EQ-5D) score was 0.86+/-0.12. The Knee injury and Osteoarthritis Outcome Score
      (KOOS) values were lower in all dimensions compared with age-matched healthy
      controls. CONCLUSION: In the long term, patients who were adolescents at the time
      of ACL reconstruction revealed significantly more radiographically visible
      osteoarthritic changes in their operated knee than in their noninvolved
      contralateral knee. Clinical outcomes and health-related quality of life are
      comparable with those of healthy controls.

PMID- 25384504
TI  - Effect of distal ulnar collateral ligament tear pattern on contact forces and
      valgus stability in the posteromedial compartment of the elbow.
AB  - BACKGROUND: It is not known whether the pattern of ulnar collateral ligament
      (UCL) tear affects elbow biomechanics. HYPOTHESIS: There will be a significant
      change in elbow biomechanics with 50% proximal but not 50% distal simulated
      rupture of the UCL. STUDY DESIGN: Controlled laboratory study. METHODS: Pressure
      sensors in the posteromedial elbow joint of 25 male cadaveric elbows (average
      age, 54.9 years; range, 26-66 years) were used to measure contact area, pressure,
      and valgus torque at 90 degrees  and 30 degrees  of elbow flexion. Thirteen
      specimens were tested with the UCL intact, then with proximal-to-distal
      detachment of 50%, and then with proximal-to-distal detachment of 100% of the
      anterior band of the UCL from the ulnar attachment. This method was repeated in
      the remaining 12 specimens in a distal-to-proximal direction. RESULTS: With 50%
      proximal-to-distal detachment, contact area decreased significantly versus intact
      at 90 degrees  (91.3 +/- 23.6 vs 112.2 +/- 26.0 mm(2); P < .001) and 30 degrees 
      (69.3 +/- 14.8 vs 83.1 +/- 21.6 mm(2); P < .001) of elbow flexion; the center of
      pressure (COP) moved significantly proximally versus intact at 90 degrees  (3.8
      +/- 2.5 vs 5.4 +/- 2.3 mm; P < .001) and 30 degrees  (5.9 +/- 2.8 vs 7.4+/-1.9
      mm; P < .001). With 50% distal-to-proximal UCL detachment versus intact, no
      significant change was observed in contact area, movement of the COP, or valgus
      laxity at either flexion position. With 100% proximal-to-distal and distal-to
      proximal detachment, significant change in contact area, movement of the COP, and
      valgus laxity versus intact was found at 90 degrees  and 30 degrees  of elbow
      flexion (P < .05). No significant difference in contact pressure was observed in
      any test conditions. CONCLUSION: Significant change in contact area and proximal
      movement of the COP with 50% proximal UCL detachment and the lack of significant
      change with 50% distal UCL detachment suggest that the proximal half of the UCL
      ulnar footprint has a primary role in maintaining posteromedial elbow
      biomechanics. CLINICAL RELEVANCE: The findings suggest that surgical
      reconstruction should aim to reestablish at least the proximal 50% of the UCL
      ulnar footprint.

PMID- 25384505
TI  - Predictors of contralateral anterior cruciate ligament reconstruction: a cohort
      study of 9061 patients with 5-year follow-up.
AB  - BACKGROUND: Identifying predictors of contralateral anterior cruciate ligament
      (ACL) reconstruction is important to focus preventive strategies and related
      research on high-risk groups. PURPOSE: To investigate predictors of contralateral
      ACL reconstruction in patients who have already undergone a primary ipsilateral
      reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This
      study was based on data from the Swedish National Knee Ligament Register from
      January 1, 2005, to December 31, 2013. Patients aged 13 to 59 years who underwent
      primary ipsilateral (index) ACL reconstruction with hamstring tendon or bone
      patellar tendon-bone autografts were included. Follow-up started on date of index
      ACL reconstruction and ended either with primary contralateral ACL
      reconstruction, after 5 years of follow-up, or on December 31, 2013, whichever
      occurred first. The investigated variables were patient sex, age at index
      reconstruction, activity at the time of index injury, timing of surgery, graft
      selection, graft harvest site, and meniscal and chondral injury. The study end
      point was primary contralateral ACL reconstruction. Relative risks (RRs) and 95%
      CIs were calculated and adjusted for confounding factors using multivariate
      statistics. RESULTS: A total of 9061 participants were included (n = 5196 males
      [57.3%] and 3865 females [42.7%]), of which 270 participants (3.0%) underwent
      primary contralateral ACL reconstruction during the 5-year follow-up. There was
      no difference in contralateral reconstruction rates between males and females
      (3.0% vs 2.9%, P = .695). Age <20 years significantly increased the risk of
      contralateral reconstruction (males: RR = 2.4 [95% CI, 1.7-3.4] and females: RR =
      2.9 [95% CI, 1.9-4.5]; P < .001). Among female patients undergoing reconstruction
      using autograft hamstring, harvest of a contralateral hamstring tendon
      significantly increased this risk (RR = 3.4 [95% CI, 1.4-7.9]; P = .006).
      CONCLUSION: In both male and female participants, age <20 years predicted an
      almost 3 times higher 5-year risk of contralateral ACL reconstruction. Among
      female participants undergoing reconstruction with autograft hamstring, a
      contralateral harvest predicted a more than 3 times higher 5-year risk of
      contralateral ACL reconstruction. Patient sex, activity at the time of index
      injury, graft selection, meniscal injury, and chondral injury were not predictors
      of contralateral ACL reconstruction.

PMID- 25384506
TI  - Knee chondrolysis by infusion of bupivacaine with epinephrine through an intra
      articular pain pump catheter after arthroscopic ACL reconstruction.
AB  - BACKGROUND: Postoperative knee chondrolysis caused by continuous intra-articular
      pain pumps infusing bupivacaine with epinephrine is a rare but serious
      complication. PURPOSE: To determine the association between postoperative intra
      articular infusion of bupivacaine with epinephrine and the development of knee
      chondrolysis in patients who have undergone arthroscopic anterior cruciate
      ligament reconstruction (ACLR). The authors hypothesized that the development of
      knee chondrolysis after ACLR is associated with postoperative high-dose intra
      articular bupivacaine with epinephrine infusion. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: In this retrospective cohort study, the charts of
      all patients treated with arthroscopic ACLR by a single surgeon between January
      1, 2004, and December 31, 2006, were reviewed. Patients with severe articular
      cartilage damage at the time of the index procedure, with known knee joint
      infection, inflammatory arthritis, multiligament knee injury, bilateral knee
      injury, or any previous knee surgery, were excluded. Patients were grouped into 2
      cohorts: the exposure group (those who had postoperative infusion of bupivacaine
      with epinephrine via an intra-articular pain pump [IAPP]) and the nonexposure
      group (those without postoperative infusion). RESULTS: A total of 105 patients
      met the inclusion and exclusion criteria. There were 57 male and 48 female
      patients with a mean age at surgery of 25.5 +/- 8.6 years (range, 13-52 years).
      The exposure group consisted of 46 patients and the control group of 59 patients.
      Thirteen of 46 patients (28.3%) who received an IAPP developed chondrolysis.
      There were no cases of chondrolysis in the control group. Of those in the
      exposure group, 32 patients were exposed to 0.5% bupivacaine with epinephrine and
      12 developed chondrolysis (37.5%), while 14 patients were exposed to 0.25%
      bupivacaine with epinephrine and 1 developed chondrolysis (7.1%). Patients
      exposed to 0.5% bupivacaine with epinephrine had a significantly higher incidence
      of chondrolysis compared with those exposed to 0.25% (P = .03). Patients with
      chondrolysis had severe pain and limitations in daily activity. CONCLUSION: The
      development of knee chondrolysis was associated with the intra-articular infusion
      of bupivacaine with epinephrine postoperatively. Furthermore, the presented
      evidence suggests that this occurs in a dose-dependent manner. The risk of knee
      chondrolysis might be reduced by avoidance of intra-articular infusion of
      bupivacaine with epinephrine. We recommend against continuous intra-articular
      infusion of local anesthetic postoperatively.

PMID- 25384507
TI  - Expression of miRNAs in non-small-cell lung carcinomas and their association with
      clinicopathological features.
AB  - Lung cancer is recognized as a leading cause of cancer-related deaths worldwide.
      Over the past several years, evidence emerged that microRNAs (miRNAs), a class of
      small non-coding RNA molecules regulating gene expression at posttranscriptional
      level, play an important role in cell functioning, as well as in human diseases.
      Here, we analyzed expression of miR-15a/16, miR-21, miR-34a, miR-126, miR-128,
      and miR-210 at transcriptional level in 30 non-small-cell lung carcinoma (NSCLC)
      tumor tissues compared to the matched adjacent normal tissues and their
      correlation with clinicopathological features of the patients. Samples were
      collected from the NSCLC patients undergoing surgery before radiotherapeutic or
      chemotherapeutic treatment. Expression levels of miRNAs were assessed by TaqMan
      RT-PCR assay. The data obtained in this study were processed using REST 2009 and
      SPSS statistical software. The graphs were designed by GraphPad prism 5.0. In
      tumor samples, we found downregulation of miR-15a/16 (50/83.3%), miR-34a (83.3%),
      miR-126 (70%), and miR-128 (63.3%). At the same time, miR-21 and miR-210 were
      upregulated by 53.3 and 66.6% in cancer tissue versus matched adjacent normal
      tissues, respectively. No significant correlation was found between the
      expression levels of miR-15a/16, miR-21, miR-34a, miR-126, miR-128, and miR-210
      and lymph node, tumor size, sex, and smoking. However, the study demonstrated a
      correlation between a change in expression of miR-15, miR-16, miR-34a, miR-126,
      and miR-210 compared to normal tissues and TNM staging (P < 0.05). Furthermore,
      miR-126 expression level was different in adenocarcinomas and squamous cell
      carcinoma (SCC) subtype (P < 0.1). Detailed analysis revealed significant change
      in expression of miR-15a/16, miR-34a, miR-126, and miR-210 in NSCLC tumor samples
      indicating involvement of these miRNAs in lung cancer pathogenesis. miR-210
      demonstrated the most consistent increase in tumor tissues between different
      patients, suggesting its potential significance for NSCLC.

PMID- 25384508
TI  - Genetic polymorphisms in the one-carbon metabolism pathway genes and
      susceptibility to non-Hodgkin lymphoma.
AB  - Corroborating evidence related to the role of aberrations on one-carbon
      metabolism (OCM) genes has been inconsistent. We evaluated the association
      between polymorphisms in 12 single nucleotide polymorphisms (SNPs) in 8 OCM genes
      (CBS, FPGS, FTHFD, MTRR, SHMT1, SLC19A1, TCN1, and TYMS), and non-Hodgkin
      lymphoma (NHL) risk in a multi-ethnic population which includes Malay, Chinese
      and Indian ethnic subgroups. Cases (N = 372) and controls (N = 722) were
      genotyped using the Sequenom MassARRAY platform. Our results of the pooled
      subjects showed a significantly enhanced NHL risk for CBS Ex9 + 33C > T (T versus
      C: OR 1.55, 95% CI 1.22-1.96, P = 0.0003), CBS Ex18-319G > A (A versus G: OR
      1.15, 95% CI 1.14-1.83; P = 0.002), SHMT1 Ex12 + 236 T > C (T versus C: OR 1.44,
      95% CI 1.15-1.81, P = 0.002), and TYMS Ex8 + 157C > T (T versus C: OR 1.29, 95%
      CI 1.06-1.57, P = 0.01). Haplotype analysis for CBS SNPs showed a significantly
      decreased risk of NHL in subjects with haplotype CG (OR 0.69, 95% CI 0.56-0.86, P
      = <0.001). The GG haplotype for the FTHFD SNPs showed a significant increased
      risk of NHL (OR 1.40, 95% CI 1.12-1.76, P = 0.002). For the TYMS gene, haplotype
      CAT at TYMS (OR 0.67, 95% CI 0.49-0.90, P = 0.007) was associated with decreased
      risk of NHL, while haplotype TAC (OR 1.29, 95% CI 1.05-1.58, P = 0.01) was found
      to confer increased risk of NHL. Our study suggests that variation in several OCM
      genes (CBS, FTHFD, SHMT1, TCN1, and TYMS) may influence susceptibility to NHL.

PMID- 25384510
TI  - Letter regarding Shen et al. entitled "The APE1 Asp148Glu polymorphism and
      colorectal cancer susceptibility: a meta-analysis".

PMID- 25384511
TI  - Mentoring Women Psychiatry Residents: Implications for Academic Leaders and
      Educators.

PMID- 25384509
TI  - Identification of OLIG2 as the most specific glioblastoma stem cell marker
      starting from comparative analysis of data from similar DNA chip microarray
      platforms.
AB  - Despite advances in surgical and adjuvant treatments, overall survival of
      glioblastoma (GBM) patients remains poor. The cancer stem cell concept suggests
      that a rare stem cell population, called glioma stem cells (GSCs), has high
      ability to self-renewal leading to recurrence in GBM. The identification of
      specific markers of GSCs would provide a powerful tool to detect and to
      characterise them in order to develop targeted therapies. We carried out a
      comparative analysis based on the identification of inter-study concordances to
      identify the genes that exhibit at best differential levels of expression between
      GSC-enriched cell cultures and differentiated tumour cell cultures from
      independent studies using DNA chip microarray technologies. We finally studied
      the protein expression of the marker we considered the most specific by
      immunohistochemistry and semi-quantitative analysis on a retrospective series of
      18 GBMs. Of the selected studies, 32 genes were retained. Among them, eight genes
      were identified to be overexpressed in GSC-enriched cultures compared to
      differentiated tumour cell cultures. Finally, among the eight genes,
      oligodendrocyte lineage transcription factor 2 (OLIG2) was characterised by the
      most different expression level in the "GSC model" compared to the
      "differentiated tumour cells model". Our approach suggests that OLIG2 is the most
      specific GSC marker; additional investigations with careful considerations about
      methodology and strategies of validation are, however, mandatory. 

PMID- 25384512
TI  - A naturally occurring nucleotide polymorphism in the orf2/folc promoter is
      associated with Streptococcus suis virulence.
AB  - BACKGROUND: Streptococcus suis is a major problem in the swine industry causing
      meningitis, arthritis and pericarditis in piglets. Pathogenesis of S. suis is
      poorly understood. We previously showed that introduction of a 3 kb genomic
      fragment from virulent serotype 2 strain 10 into a weakly virulent serotype 2
      strain S735, generated a hypervirulent isolate. The 3 kb genomic fragment
      contained two complete open reading frames (ORF) in an operon-structure of which
      one ORF showed similarity to folylpolyglutamate synthetase, whereas the function
      of the second ORF could not be predicted based on database searches for protein
      similarity. RESULTS: In this study we demonstrate that introduction of orf2 from
      strain 10 into strain S735 is sufficient to dramatically increase the virulence
      of S735 in pigs. This increase in virulence could not be associated with changes
      in pro-inflammatory responses of porcine blood mononucleated cells in response to
      S. suis in vitro. Sequence analysis of the orf2-folC-operon of S. suis isolates
      10 and S735 revealed an SNP in the -35 region of the putative promoter sequence
      of the operon, as well as several SNPs resulting in amino acid substitutions in
      the ORF2 protein. Transcript levels of orf2 and folC were significantly higher in
      the virulent strain 10 than in the weakly virulent strain S735 and in vitro
      mutagenesis of the orf2 promoter confirmed that this was due to a SNP in the
      predicted -35 region upstream of the orf2 promoter. In this study, we
      demonstrated that the stronger promoter was present in all virulent and highly
      virulent S. suis isolates included in our study. This highlights a correlation
      between high orf2 expression and virulence. Conversely, the weaker promoter was
      present in isolates known to be weakly pathogenic or non-pathogenic. CONCLUSION:
      In summary, we demonstrate the importance of orf2 in the virulence of S. suis.

PMID- 25384513
TI  - Quantification of upper limb skills in elderly rehabilitative inpatients: a
      controlled study.
AB  - BACKGROUND: Aging has a recognized degenerative effect on the functionality of
      the hand in terms of strength and dexterity. Despite this, there are few studies
      in literature that quantify the upper limb skills in the elderly. AIM: The aim
      was to present quantitative data regarding upper limb functionality in the
      elderly and to quantify the effect of aging on them, considering the influence of
      the comorbidities, of the global level of autonomy, of the cognitive status and
      of the mood, which are typically compromised in the elderly. DESIGN: It was a
      controlled study. SETTING: It was settled in the Rehabilitation Unit of the
      "Santa Maria alle Fonti" Medical Center, part of the Don Carlo Gnocchi ONLUS
      Foundation. POPULATION: Thirty-five elderly inpatients (aged 78.6+/-7.5 years)
      compared to 30 healthy young adults (aged 30+/-3.9 years). METHODS: A task
      consisting in 12 trials of grasping of rulers was administered to each subject
      and studied with a video analysis software. To assess the comorbidities, the
      global level of autonomy, the cognitive status and the mood, we respectively used
      the Cumulative Illness Rating Scale (CIRS), the Functional Independence Measure
      (FIMTM), the Mini Mental State Examination (MMSE) and the Geriatric Depression
      Scale in the 15-items version (GDS-15). The scores obtained in these scales were
      correlated to the mean times of trials execution. RESULTS: The motor performance
      was significantly worse in the inpatients group compared to the control group in
      terms of time to complete single tasks (which was on average three times higher
      in the inpatients group) and of respect of the starting sound stimulus, with more
      subjects from the inpatients group anticipating the starting signal. This
      worsening of the motor performance was significantly correlated to the severity
      of comorbidities and to the global level of autonomy. No significant differences
      emerged for the correctness of the performance and significant differences were
      not correlated with depression or cognitive impairment. CONCLUSION: This study
      provides quantifiable data regarding upper limb skills in the elderly inpatient,
      allowing comparisons with other future studies of the rehabilitative environment.
      CLINICAL REHABILITATION IMPACT: It suggests the relevance of considering the
      severity of comorbidities and the global level of autonomy in the assessment of
      upper limb skills in the elderly.

PMID- 25384514
TI  - Resistance exercise training improves heart rate variability and muscle
      performance: a randomized controlled trial in coronary artery disease patients.
AB  - BACKGROUND: Resistance exercise (RE) is an important part of cardiac
      rehabilitation. However, it is not known about the low intensity of RE training
      that could modify the heart rate variability (HRV), muscular strength and
      endurance in patients with coronary artery disease (CAD). AIM: To investigate the
      effects of high repetition/low load resistance training (HR/LL-RT) program on HRV
      and muscular strength and endurance in CAD patients. DESIGN: Randomized and
      controlled trial. SETTING: Patients seen at the Cardiopulmonary Physical Therapy
      Laboratory between May 2011 and November 2013. POPULATION: Twenty male patients
      with CAD were randomized to a training group (61.3+/-5.2 years) or control group
      (61+/-4.4 years). METHODS: 1 repetition maximum (1-RM) maneuver, discontinuous
      exercise test on the leg press (DET-L), and resting HRV were performed before and
      after 8 weeks of HR/LL-RT on a 45 degrees  leg press. RMSSD, SD1, mean HR and
      ApEn indices were calculated. The HR/LL-RT program consisted of a lower limb
      exercise using a 45 degrees  leg press; 3 sets of 20 repetitions, two times a
      week. The initial load was set at 30% of the 1-RM load and the duration of the
      HR/LL-RT program was performed for 8 weeks. RESULTS: After 8 weeks of HR/LL-RT
      there were significant increases of RMSSD and SD1 indices in the training group
      only (P<0.05). There was a significant decrease in mean HR after HR/LL-RT in the
      training group (P<0.05). There was a significantly higher ApEn after in the
      training group (P<0.05). There were significantly higher values in the training
      group in contrast to the control group (P<0.05). CONCLUSION: These results show
      positive improvements on HRV, as well as muscle strength and endurance in CAD
      patients. CLINICAL REHABILITATION IMPACT: Eight weeks of HR/LL-RT is an effective
      sufficient to beneficially modify important outcomes as HRV, muscle strength and
      endurance in CAD patients.

PMID- 25384515
TI  - Integration to focal vibration in neurorehabilitation.

PMID- 25384516
TI  - Rad54B serves as a scaffold in the DNA damage response that limits checkpoint
      strength.
AB  - The strength of the DNA damage checkpoint critically influences cell fate, yet
      the mechanisms behind the fine tuning of checkpoint strength during the DNA
      damage response (DDR) are poorly understood. Here we show that Rad54B--a SNF2
      helicase-like DNA-repair protein--limits the strength of both the G1/S and G2/M
      checkpoints. We find that Rad54B functions as a scaffold for p53 degradation via
      its direct interaction with the MDM2-MDMX ubiquitin-ligase complex. During the
      early phases of the DDR, Rad54B is upregulated, thereby maintaining low
      checkpoint strength and facilitating cell cycle progression. Once the p53
      mediated checkpoint is established, Rad54B is downregulated, and high checkpoint
      strength is maintained. Constitutive upregulation of Rad54B activity, which is
      frequently observed in tumours, promotes genomic instability because of
      checkpoint override. Thus, the scaffolding function of Rad54B dynamically
      regulates the maintenance of genome integrity by limiting checkpoint strength.

PMID- 25384518
TI  - Response to: Importance of work-life balance among German medical students who
      wish to become gynecologists.

PMID- 25384519
TI  - Umbilical cord blood adipokines and newborn weight change.
AB  - PURPOSE: To ascertain the association between umbilical cord levels of
      adiponectin, leptin and resistin, and birth weight (BW) and newborn weight change
      (NWC) in the first 96 h of life. METHODS: 392 full-term singletons were
      recruited, in 2005/2006, at the five public units providing obstetrical and
      neonatal care in Porto. Information was collected by face-to-face interview and
      additionally from clinical records. Umbilical cord blood adipokines levels were
      determined and categorized using the 10th and 90th percentiles. Anthropometrics
      were obtained by trained examiners and NWC estimated as (weight - BW)/BW * 100,
      adjusted for newborn's age. Regression coefficients and 95% confidence intervals
      were calculated. RESULTS: Low leptin levels (<=5.6 ng/ml) were associated with
      lower BW (beta = -137.3 g 95%CI -268.6 g, -6.1 g) and high leptin levels (>=30.7
      ng/ml) were associated with higher BW (beta = 276.3 g 95%CI 145.8 g, 406.8 g) and
      higher NWC (beta = 1.10% 95% CI 0.29%, 1.92%), comparing to newborns with normal
      leptin levels. Adiponectin and resistin were not associated with BW or NWC.
      CONCLUSION: High umbilical cord blood leptin levels predicted higher BW and lower
      weight loss in the immediate postnatal period.

PMID- 25384520
TI  - Effect of myocardial infarction on female sexual function in women.
AB  - PURPOSE: The aim of this study was to assess sexual function in female patients
      with myocardial infarction (MI). METHODS: As research instruments, an interview
      form of 20 questions that questioned personal characteristics was developed by
      researchers, Female Sexual Function Index (FSFI) that evaluated sexual
      dysfunction was used. The Beck Depression Inventory was used to evaluate
      depression. RESULTS: In the course of this study, 45 female patients (62.73 +/-
      8.55 years) with MI and 50 control women were interviewed. The total FSFI score
      was 16.41 +/- 8.04 in the MI group versus 23.13 +/- 3.95 (P < 0.001) in the
      control group. The prevalence of sexual dysfunction is significantly higher and
      the mean FSFI score was significantly lower in MI group women in comparison with
      the control group. Subscale scores of desire, arousal, lubrication and orgasm
      domains were lower than the other subscale scores in the MI group. Besides, 75.6%
      of the women in the MI group and 48.2% of women in the control group had a female
      sexual dysfunction. The frequency of intercourse was significantly lower in women
      with MI (1.55 +/- 0.50 times last month) compared to the control group (2.14 +/-
      1.04 times last month). No significant differences were detected between the mean
      total BDI scores. But the correlation between FSFI and BDI total scores indicates
      that the increasing BDI scores in MI and control groups affected the total FSFI
      scores negatively. CONCLUSION: Sexual problems are frequent in women with MI.
      Sexuality should be evaluated after MI and patients' education and counseling may
      contribute to a better sexual function.

PMID- 25384521
TI  - Proliferation of trophoblasts and Ki67 expression in preeclampsia.
AB  - BACKGROUND/AIMS: Preeclampsia is a pregnancy-specific disease with the increased
      risk of maternal morbidity and mortality. It is characterised by placental
      vascular dysfunction. Despite the numerous studies on preeclampsia, studies
      evaluating proliferation of villous trophoblasts in preeclamptic placentas are
      limited. Ki67 is a proliferation marker that expresses in the nuclei of
      proliferating cells. In this study, we examined the proliferation of villous
      trophoblasts in placentas of preeclamptic patients by using Ki67 and compared it
      with placentas of normal pregnant patients. MATERIAL AND METHODS: The current
      study is a prospective one, including 15 placentas from preeclamptic patients and
      14 placentas from normal pregnancies as controls. For detection of proliferation
      in villous trophoblasts, Ki67 was used. RESULTS: The Ki67 index was 11.48+/-1.67%
      in normal patients and 15.53+/-2.28% in preeclamptic patients. There was a
      difference in Ki67 index between the two groups (p < 0.001). CONCLUSION: Our
      results support the opinion that trophoblasts undergo regeneration hyperplasia as
      a result of injuries arising on the villous surface in preeclampsia.
      Proliferation of trophoblasts may contribute the development of preeclampsia.

PMID- 25384522
TI  - A short-range ordered-disordered transition of a NiOOH/Ni(OH)2 pair induces
      switchable wettability.
AB  - By virtue of its amorphous structure with a short-range order feature, the
      inorganic nanoporous nickel oxyhydroxide (NiOOH) can reversibly and rapidly
      switch wettability by alternate treatments of environmental chamber
      (superhydrophobic) and UV/ozone (superhydrophilic). The switchable mechanism of
      the NiOOH/Ni(OH)2 pair arising from its exceptional intrinsic short-range order
      disorder transition together with chemical composition change is highlighted for
      the first time, which significantly differs from the current stimuli-responsive
      materials. This distinct multifunctional thin film not only possesses reversible
      wettability but also is optically patternable/repairable and electrically
      conductive, which could be applicable in the manufacturing of various micro- and
      nanostructures. We demonstrate this potential in the rewritable two-dimensional
      (2D) microfluidic channels and wetting-contrast enhanced selective
      electroplating. 

PMID- 25384523
TI  - Familial and sporadic schizophrenia: a comparison of somatic diseases and abuse
      in patients and their relatives.
AB  - OBJECTIVE: Comparing schizophrenia patients on the basis of familial and non
      familial forms of the illness provides a promising approach to the identification
      of genes involved in schizophrenia. The aim of this study was to search for
      somatic factors that discriminate between patients with and without a family
      history of schizophrenia and between their relatives. METHODS: Ninety-five
      schizophrenia patients were structurally interviewed about mental and physical
      health and alcohol and substance use in themselves and their families. Besides
      this, complementary information was obtained from the patients' case records.
      Patients with (41%) and without (59%) a family history were then compared.
      RESULTS: The main differences were found in the patients' relatives. Fewer
      patients with a family history, compared with patients without a family history,
      had relatives with cancer (p = 0.002). Conversely, there was a tendency towards
      that more patients with a family history, compared with patients without a family
      history, had relatives with cardiac infarction (p = 0.05). CONCLUSION: The
      genetic risk associated with schizophrenia seems to cosegregate into a factor(s)
      that protects against cancer and possibly also increases the risk for cardiac
      infarction.

PMID- 25384524
TI  - Association of glucocorticoid receptor polymorphisms with the susceptibility to
      major depressive disorder and treatment responses in Korean depressive patients.
AB  - OBJECTIVE: Major depressive disorder (MDD) is closely related to stress reactions
      and serotonin probably underpins the pathophysiology of MDD. Alterations of the
      hypothalamic-pituitary-adrenal axis at the gene level have reciprocal
      consequences on serotonin neurotransmission. Glucocorticoid receptor (GR)
      polymorphisms affect glucocorticoid sensitivity, which is associated with
      cortisol feedback effects. Therefore, we hypothesised that GR polymorphisms are
      associated with the susceptibility to MDD and predict the treatment response.
      METHOD: Ninety-six subjects with a minimum score of 17 on the 21-item Hamilton
      Depression Scale (HAMD) at baseline were enrolled into the present study. The
      genotypes of GR (N363S, ER22/23EK, Bcl1, and TthIII1 polymorphisms) were
      analysed. The HAMD score was again measured after 1, 2, 4 and 8 weeks of
      antidepressant treatment to detect whether the therapeutic effects differed with
      the GR genotype. RESULTS: Our subjects carried no N363S or ER22/23EK genetic
      polymorphisms and three types of Bcl1 and TthIII1 genetic polymorphisms. The C/C
      genotype and C allele at Bcl1 polymorphism were more frequent in MDD patients
      than in normal controls (p < 0.01 and p = 0.01, respectively). The genotype
      distributions did not differ significantly between responders and non-responders.
      CONCLUSION: These results suggest that GR polymorphism cannot predict the
      therapeutic response after antidepressant administration. However, GR
      polymorphism (Bcl1) might play a role in the pathophysiology of MDD. Future
      studies should check this finding in larger populations with different
      characteristics.

PMID- 25384525
TI  - Battery for assessment of neuropsychological status (RBANS) in schizophrenia: a
      pilot study in the Spanish population.
AB  - OBJECTIVES: The aims of this study were to research the following issues in a
      Spanish population of patients with schizophrenia. (a) The sensitivity and
      reliability of the Repeatable Battery for the Assessment of Neuropsychological
      Status (RBANS) to detect cognitive impairment in schizophrenia. (b) The
      convergent validity of RBANS on a larger battery of neuropsychological tests
      sensitive to the cognition disorders typically observed in schizophrenia. (c) The
      correlates of poor performance in RBANS with clinical features and illness
      severity. METHOD: Thirty schizophrenia patients, 30 non-psychotic patients and 30
      healthy participants were assessed using RBANS (form A). We administered a
      battery of neuropsychological tests and four scales to evaluate patient's
      clinical status. RESULTS: Schizophrenia patients and non-psychotic patients
      performed significantly worse than healthy controls on RBANS, and schizophrenia
      patients performed slightly worse than non-psychiatric controls, but this
      difference was not significant. Good inter-test reliability and concurrent
      validity were found. Only a moderate correlation between RBANS performance and
      illness severity was observed. CONCLUSIONS: RBANS revealed coherence in
      identifying cognitive impairment in schizophrenia patients of a different
      cultural background, and it is shown to be a sensitive, valid and easy-to-perform
      tool for the neuropsychological assessment of Spanish patients with
      schizophrenia.

PMID- 25384526
TI  - Effect of quetiapine on cognitive function in schizophrenia: a mismatch
      negativity potentials study.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the effects of
      quetiapine on abnormalities of early auditory processing in patients with
      schizophrenia were reflected by mismatch negativity (MMN). METHODS: Subjects were
      23 patients with schizophrenia and 23 controls. Psychopathology was rated in
      patients with the Positive and Negative Syndrome Scale (PANSS) at baseline and
      after 4-week and after 8-week treatments with quetiapine. Auditory stimuli for
      event-related potentials consisted of 100 ms/1000 Hz standards, intermixed with
      100 ms/1500 Hz frequency deviants and 250 ms/ 1000 Hz duration deviants. A
      stimulus onset asynchrony of each was 300 ms. Electroencephalograph was recorded
      at Fz. BESA 5.1.8 was used to perform data analysis. MMN waveforms were obtained
      by subtracting waveforms elicited by standards from those elicited by frequency-
      or duration-deviant stimuli. RESULTS: Quetiapine decreased all PANSS scores.
      Patients showed smaller mean amplitudes of frequency and duration MMN at baseline
      than did controls. A repeated measure analysis of variance with sessions (i.e.
      baseline and 4- and 8-week treatments) and MMN type (frequency versus duration)
      as within-subject factors revealed no significant MMN type or MMN type * session
      main effect for MMN amplitudes (for MMN type: F = 0.704, df = 1, p = 0.403; for
      MMN type * session: F = 0.299, df = 2, p = 0.796). Session main effect was
      significant (F = 3.576, df = 2, p = 0.031). Least square difference tests showed
      significant differences between MMN amplitudes at 8 weeks and those at both
      baseline (p = 0.025) and 4 weeks (p = 0.020). MMN amplitudes at 8 weeks were
      higher than those at baseline. CONCLUSIONS: Quetiapine improved the amplitudes of
      MMN after the 8-week treatment. MMN offers objective evidence that treatment with
      the quetiapine may ameliorate preattentive deficits in schizophrenia.

PMID- 25384527
TI  - Increasing risks of human dirofilariasis in travelers.
AB  - BACKGROUND: Dirofilariasis is a zoonotic nematode infection of domestic and wild
      carnivores that can be transmitted to man by infected mosquitoes. METHODS:
      Internet search engines were queried with the key words to examine case reports,
      series, and descriptive analyses of animal and human dirofilariasis to meet the
      objectives of this review to describe the increasing prevalence of animal and
      human dirofilariasis worldwide; to resolve misconceptions regarding the
      pathophysiology and outcomes of animal versus human dirofilariasis; and to
      recommend new strategies for the diagnosis, management, and prevention of human
      dirofilariasis in travelers. RESULTS: Descriptive epidemiological studies in the
      United States and Europe have now established dirofilariasis as an emergent
      parasitic disease of dogs and man. Global warming has extended the mosquito
      vector-borne transmission cycles, enzootic distributions, and canine
      microfilarial prevalences of the disease to non-endemic regions. CONCLUSIONS:
      Travel medicine clinicians must remain vigilant regarding the possibilities of
      human pulmonary dirofilariasis when solitary "coin lesions" appear on screening
      chest X-rays or abdominal neuroimaging studies in asymptomatic patients without
      peripheral hypereosinophilia. The least invasive diagnostic methods are
      recommended. Future investigations should focus on conducting active
      epidemiological surveillance for dirofilariasis in humans and animals; on
      improving canine dirofilarial chemoprophylaxis; and on developing new, rapid
      molecular methods for diagnosing and differentiating human dirofilarial
      infections.

PMID- 25384528
TI  - Determination of vancomycin minimum inhibitory concentration for ceftazidime
      resistant Streptococcus pneumoniae in Iran.
AB  - BACKGROUND: In the context of growing health concerns over antibiotic resistance,
      the evaluation of the minimum inhibitory concentration (MIC) of vancomycin for
      Streptococcus pneumoniae (S. pneumoniae) strains resistant to ceftazidime becomes
      important for guiding health policy makers. The aim of this study was to
      determine vancomycin MIC of ceftazidime resistant S. pneumoniae strains. METHODS:
      Fifty identified serotypes of ceftazidime resistant S. pneumoniae strains were
      included in the study. The vancomycin MIC of the above mentioned bacteria was
      determined based on the 0.5 McFarland standards, by using a microdilution broth
      and the Etest method. RESULTS: The results showed that out of 50 ceftazidime
      resistant strains of S. pneumoniae, 46 strains (92%) have shown a vancomycin MIC
      <=0.19 - 0.1.5 MUg/ml and only four strains (8%) have shown a vancomycin MIC
      equal to 1.5 MUg/ml and the related maximum zone of inhibition was of 10
      millimeter diameters. CONCLUSIONS: The results of this investigation point out
      the emergence of S. pneumoniae strains with a vancomycin MIC >=1.5 MUg/ml, which
      were resistant to ceftazidime. This finding uncovers a major health concern: a
      vancomycin MIC higher than 1.5 MUg/ml and maximum zone of inhibition of only 10
      millimeter. These findings represent an important warning for health authorities
      globally, concerning the treatment of patients, as the occurrence of S.
      pneumoniae strains with decreased vancomycin susceptibility has been
      demonstrated.

PMID- 25384529
TI  - The Human Variome Project: ensuring the quality of DNA variant databases in
      inherited renal disease.
AB  - A recent review identified 60 common inherited renal diseases caused by DNA
      variants in 132 different genes. These diseases can be diagnosed with DNA
      sequencing, but each gene probably also has a thousand normal variants. Many more
      normal variants have been characterised by individual laboratories than are
      reported in the literature or found in publicly accessible collections. At
      present, testing laboratories must assess each novel change they identify for
      pathogenicity, even when this has been done elsewhere previously, and the
      distinction between normal and disease-associated variants is particularly an
      issue with the recent surge in exomic sequencing and gene discovery projects. The
      Human Variome Project recommends the establishment of gene-specific DNA variant
      databases to facilitate the sharing of DNA variants and decisions about likely
      disease causation. Databases improve diagnostic accuracy and testing efficiency,
      and reduce costs. They also help with genotype-phenotype correlations and
      predictive algorithms. The Human Variome Project advocates databases that use
      standardised descriptions, are up-to-date, include clinical information and are
      freely available. Currently, the genes affected in the most common inherited
      renal diseases correspond to 350 different variant databases, many of which are
      incomplete or have insufficient clinical details for genotype-phenotype
      correlations. Assistance is needed from nephrologists to maximise the usefulness
      of these databases for the diagnosis and management of inherited renal disease. 

PMID- 25384530
TI  - Success of eculizumab in the treatment of atypical hemolytic uremic syndrome.
AB  - BACKGROUND: Disorders of complement regulation are the most important etiology of
      atypical hemolytic uremic syndrome (aHUS). Recent studies demonstrate that
      eculizumab is beneficial in long-term aHUS treatment. We present a series of
      children with aHUS resistant to/dependent on plasma exchange (PE) who were
      treated with eculizumab. METHODS: This was a retrospective study in which data
      were retrieved from the medical files of children who had received PE as
      treatment for aHUS. The data retrieved included age, sex, presenting symptoms,
      presence of diarrhea/vomiting, hospitalization duration, laboratory data on
      admission and follow-up, need for transfusion or dialysis, response to PE,
      response to eculizumab and outcome. RESULTS: Of the 15 children diagnosed with
      aHUS in 2011 and 2012 in our departments, ten were resistant to, or dependent on,
      plasma therapy and treated with eculizumab; these children were enrolled in the
      study. Three patients had relapses, and seven had a new diagnosis. Nine children
      had oliguria or anuria, and eight required dialysis. Hypertension was observed in
      six patients. Neurologic involvement developed in six patients, with the symptoms
      including seizures, loss of balance, vision loss and severe confusion. Five and
      five patients were resistant to and dependent on plasma therapy, respectively.
      Following the start of eculizumab treatment, all patients achieved full recovery
      of renal function and hematologic parameters. CONCLUSIONS: In our ten pediatric
      patients with aHUS who did not respond to PE, eculizumab was a lifesaving therapy
      and improved their quality of life. Early eculizumab use was a rescue therapy for
      renal function. Our results show that eculizumab is an effective treatment for
      aHUS. However, more studies are needed on the long-term efficacy and safety of
      eculizumab in children with aHUS and to determine the optimal duration of
      treatment.

PMID- 25384531
TI  - A case of mid-apical obstructive hypertrophic cardiomyopathy treated with a
      transapical myectomy approach: a case report.
AB  - INTRODUCTION: Hypertrophic cardiomyopathy is a genetic cardiac disease
      characterized by marked variability in morphological expression and natural
      history. The hypertrophic myocardium is often confined to the septum or lateral
      wall of the left ventricle, but it can also be encountered in the middle or
      apical segments of the myocardium. Treatment is based on medical therapy. Others
      therapies, such as embolization of the septal artery or ventriculomyectomy, are
      indicated in special situations. Surgery is the standard treatment, and it is
      classically done via a transaortic approach; however, in cases in which the
      hypertrophic myocardium is confined to mid-apical segments, a transapical
      approach is an option. Only a few cases of mid-apical obstructive hypertrophic
      cardiomyopathy treated with a myectomy using a transapical approach have been
      reported in the English-language literature. In this report, we present a case of
      a patient with mid-apical obstructive hypertrophic cardiomyopathy treated using
      this new approach. CASE PRESENTATION: A 63-year-old Caucasian woman presented
      with a history of chest pain and shortness of breath causing significant
      limitations on her daily life activities. She had a history of coronary artery
      disease. Her physical examination was unremarkable. Transthoracic
      echocardiography revealed normal systolic function and significant concentric
      left ventricular hypertrophy that was greater in the mid-apical region. Nuclear
      magnetic resonance imaging confirmed significant hypertrophy of the median
      segments of the left ventricle. The patient had persistent symptoms despite
      receiving optimized medical treatment, and a surgical approach was indicated. As
      a myectomy using transaortic technique was thought to be difficult to perform in
      her case, a transapical approach was used. No complications occurred, and her
      symptoms resolved. CONCLUSION: A transapical myectomy should be taken into
      consideration for patients with mid-apical obstructive hypertrophic
      cardiomyopathy that is refractory to medical treatment.

PMID- 25384532
TI  - Mechanism of spin crossover in LaCoO3 resolved by shape magnetostriction in
      pulsed magnetic fields.
AB  - In the scientific description of unconventional transport properties of oxides
      (spin-dependent transport, superconductivity etc.), the spin-state degree of
      freedom plays a fundamental role. Because of this, temperature- or magnetic field
      induced spin-state transitions are in the focus of solid-state physics.
      Cobaltites, e.g. LaCoO3, are prominent examples showing these spin transitions.
      However, the microscopic nature of the spontaneous spin crossover in LaCoO3 is
      still controversial. Here we report magnetostriction measurements on LaCoO3 in
      magnetic fields up to 70 T to study the sharp, field-induced transition at Hc ~
      60 T. Measurements of both longitudinal and transversal magnetostriction allow us
      to separate magnetovolume and magnetodistortive changes. We find a large increase
      in volume, but only a very small increase in tetragonal distortion at Hc. The
      results, supported by electronic energy calculations by the configuration
      interaction cluster method, provide compelling evidence that above Hc LaCoO3
      adopts a correlated low spin/high spin state.

PMID- 25384533
TI  - Cognitive Vulnerabilities for Depression and Anxiety in Childhood: Specificity of
      Anxiety Sensitivity and Rumination.
AB  - BACKGROUND: Childhood anxiety and depression frequently co-occur. Exploring
      specificity in cognitive processes for anxiety and depression in childhood can
      provide insight into cognitive vulnerabilities contributing to the development of
      anxiety and depressive disorders and inform targeted psychological interventions.
      Anxiety sensitivity and rumination are robust cognitive vulnerabilities for
      anxiety and depression, respectively. However, despite conceptual similarities,
      they are rarely considered together within a single study. AIMS: The current
      study explored specific and shared associations between anxiety sensitivity
      subscales and rumination and anxiety and depressive symptoms in unselected
      children. METHOD: Multiple regression analyses explored to what extent specific
      self-reported anxiety sensitivity subscales (physical, social and mental
      concerns) and rumination predicted anxiety and depressive symptoms in 147
      unselected children, aged 7-11 years. RESULTS: Physical and social concern
      subscales of anxiety sensitivity were specifically associated with anxiety,
      whilst rumination was specifically associated with depressive symptoms. The
      mental concerns subscale of anxiety sensitivity was independently associated with
      both anxiety and depressive symptoms. These associations were only partially
      mediated by rumination. CONCLUSIONS: Anxiety and depression in young people are
      characterized by specific and shared cognitions. Evidence for shared and specific
      associations between the cognitive vulnerabilities of anxiety sensitivity and
      rumination, and anxiety and depression highlight the utility of transdiagnostic
      research and confirm that cognitive therapies may benefit from targeting
      cognitive concerns relating specifically to the patient's presenting symptoms.

PMID- 25384534
TI  - Optimization of preservation and processing of sea anemones for microbial
      community analysis using molecular tools.
AB  - For several years, knowledge on the microbiome associated with marine
      invertebrates was impaired by the challenges associated with the characterization
      of bacterial communities. With the advent of culture independent molecular tools
      it is possible to gain new insights on the diversity and richness of
      microorganisms associated with marine invertebrates. In the present study, we
      evaluated if different preservation and processing methodologies (prior to DNA
      extraction) can affect the bacterial diversity retrieved from snakelocks anemone
      Anemonia viridis. Denaturing gradient gel electrophoresis (DGGE) community
      fingerprints were used as proxy to determine the bacterial diversity retrieved
      (H'). Statistical analyses indicated that preservation significantly affects H'.
      The best approach to preserve and process A. viridis biomass for bacterial
      community fingerprint analysis was flash freezing in liquid nitrogen
      (preservation) followed by the use of a mechanical homogenizer (process), as it
      consistently yielded higher H'. Alternatively, biomass samples can be processed
      fresh followed by cell lyses using a mechanical homogenizer or mortar &pestle.
      The suitability of employing these two alternative procedures was further
      reinforced by the quantification of the 16S rRNA gene; no significant differences
      were recorded when comparing these two approaches and the use of liquid nitrogen
      followed by processing with a mechanical homogenizer. 

PMID- 25384535
TI  - Detailed profiling of anti-desmoglein autoantibodies identifies anti-Dsg1
      reactivity as a key driver of disease activity and clinical expression in
      pemphigus vulgaris.
AB  - With their near-universal presence in patients and ease of clinical measurement,
      anti-desmoglein (Dsg) antibodies serve as primary candidates for creating
      prognostic tools in Pemphigus vulgaris (PV). Although the desmoglein compensation
      hypothesis postulates a clear relationship between anti-Dsg autoantibodies and
      clinical phenotype in PV, recent studies have questioned the fidelity of this
      hypothesis as a predictor of lesion morphology. Moreover, few studies address the
      association of anti-Dsg antibodies to other clinical parameters such as disease
      phase and age at onset. Using the largest patient repository to date in PV, we
      present a detailed analysis of anti-desmoglein antibody profiles across a
      comprehensive range of dynamic (disease phase, therapy, lesion morphology) and
      temporal (disease duration, age at sampling, age at onset) clinical parameters.
      Our data highlight the non-traditional but key role of anti-Dsg1 levels in
      tracking disease activity. We show that declining anti-Dsg1 levels may predict
      progression from active phase to early remission and long-term maintenance of
      remission, regardless of lesion morphology. In contrast, many remittent patients
      have elevated levels of anti-Dsg3 without lesional activity. Furthermore, we
      describe a unique subset of remittent patients that develop chronic transient
      lesions (lasting <1 week) in the setting of elevated anti-Dsg3 levels but do not
      meet the consensus criteria for active phase. Re-classification of patients with
      transient lesions as "active" may shed new light on pathophysiological processes
      underlying cycles of blister formation and rapid spontaneous healing in PV.
      Additionally, we provide evidence for the potential attenuation of the immune
      response with prolonged disease duration. Our data fit into the broader effort of
      immunoprofiling to promote data-informed decision-making regarding diagnosis,
      prognosis and treatment of complex diseases. 

PMID- 25384536
TI  - Development of a reverse genetics system based on RNA polymerase II for Newcastle
      disease virus genotype VII.
AB  - Newcastle disease virus (NDV) has only a single serotype but diversified
      genotypes. Genotype VII strains are the prevalent currently circulating genotype
      worldwide, and in particular, these strains cause outbreaks in waterfowl. In this
      study, a reverse genetics system for highly virulent NDV isolated from goose
      flocks was developed independent of conventional T7 RNA polymerase. Infectious
      virus was successfully generated by an RNA polymerase II promoter to drive
      transcription of the full-length virus antigenome. A green fluorescent protein
      (GFP)-expressing virus was generated by inserting an additional transcription
      cassette coding for the enhanced GFP between the P and M genes of the genome. The
      expression of GFP was confirmed by western blotting and fluorescence microscopy.
      The replication kinetics and pathogenicity of the recombinant viruses are
      indistinguishable from the parental wild-type virus. This reverse genetics system
      will provide a powerful tool for the analysis of goose-origin NDV dissemination
      and pathogenesis, as well as preparation for genotype-matched NDV attenuated
      vaccines. 

PMID- 25384537
TI  - First report of Bluetongue virus isolation in the Republic of Korea and analysis
      of the complete coding sequence of the segment 2 gene.
AB  - This study investigated the possible presence of the Bluetongue virus (BTV) in
      the Republic of Korea (ROK). Cell cultures were used to test blood samples
      collected from abattoirs throughout the country. Testing identified a single BTV
      isolate, which was characterized as BTV serotype 1 based on a nucleotide sequence
      analysis of the segment 2 gene. This report therefore indicates that BTV serotype
      1 is present in the ROK. The potential importance of BTV in the ROK has been
      overlooked because cattle are mostly unaffected by the virus and because sheep,
      the most severely infected hosts, are uncommon in the ROK. However, as recent BTV
      serotype 8 outbreaks in Europe have demonstrated, certain BTV strains have the
      potential to cause severe disease in cattle. Additionally, with climate change
      continuously expanding the regions in which Culicoides vectors are able to
      survive, there is an increased need to study BTV in the Far East and ROK. To
      better prepare for future outbreaks of BTV, a sustained and effective level of
      surveillance for BTV in livestock will need to be established. 

PMID- 25384538
TI  - Evaluation of back projection methods for breast tomosynthesis image
      reconstruction.
AB  - Breast cancer is the most common cancer among women in the USA. Compared to
      mammography, digital breast tomosynthesis is a new imaging technique that may
      improve the diagnostic accuracy by removing the ambiguities of overlapped tissues
      and providing 3D information of the breast. Tomosynthesis reconstruction
      algorithms generate 3D reconstructed slices from a few limited angle projection
      images. Among different reconstruction algorithms, back projection (BP) is
      considered an important foundation of quite a few reconstruction techniques with
      deblurring algorithms such as filtered back projection. In this paper, two BP
      variants, including alpha-trimmed BP and principal component analysis-based BP,
      were proposed to improve the image quality against that of traditional BP.
      Computer simulations and phantom studies demonstrated that the alpha-trimmed BP
      may improve signal response performance and suppress noise in breast
      tomosynthesis image reconstruction. 

PMID- 25384539
TI  - PACS used while on-call: a national survey of radiology program directors and
      chief residents.
AB  - The aim of this study was to determine the prevalence of different diagnostic
      image viewing platforms used by radiologists while on-call, and to assess the
      opinions and preferences of radiology program directors and chief residents
      regarding their use. An online survey was sent electronically to radiology
      residency program directors and chief residents via the Association of University
      Radiologists. Forty-two radiology program directors and 25 chief residents
      completed the survey, yielding response rates of 24.9 and 8.5 %, respectively.
      From the survey results, 10 different Picture Archiving Communications Systems
      (PACS) were identified; GE (25 %), Philips (17 %), and Agfa Impax (15 %) were the
      most prevalent. Interestingly, only 5 % of all respondents use a secondary
      "Digital Imaging and Communications in Medicine" viewer for on-call studies.
      Perceptions of PACS functionality were generally neutral to weakly positive. Most
      respondents strongly agreed that it is important to have a single integrated PACS
      for viewing on-call studies and agreed that the PACS should be integrated into
      the Electronic Medical Records (EMR). The overwhelming majority of respondents
      use their institution's PACS while on-call. The results show there is still a
      wide variety of PACS platforms used by different institutions; however, GE,
      Phillips, and Agfa were some of the most prevalent. Most radiologists surveyed
      have neutral to slightly positive perceptions about the functionality and ease of
      use of their PACS. Finally, while radiologists agree that PACS should be
      integrated with EMR, only 53 % of respondents currently have this arrangement. 

PMID- 25384540
TI  - Huge kidneys in a patient with chronic lymphocytic leukaemia.

PMID- 25384541
TI  - A monomeric [Zr(CO3)4](4-) complex in an ammonium zirconium carbonate aqueous
      solution studied by extended X-ray absorption fine structure, Raman and nuclear
      magnetic resonance spectroscopy.
AB  - The speciation of zirconium complexes in ammonium zirconium carbonate (AZC)
      solutions should be further studied in order to develop high-performance AZC
      complexes for use in elaborate industrial materials. Thus, the speciation and the
      structure of various zirconium species in ammonium zirconium carbonate solutions
      were investigated over a wide range of total carbonate and ammonium
      concentrations. By employing extended X-ray absorption fine structure analysis,
      and Raman and (13)C NMR spectroscopy, it was found that four carbonate ions
      coordinate bidentately to the zirconium ion. In addition, the exact concentration
      ranges of carbonate and ammonium in AZC necessary to generate the monomeric
      zirconium carbonate complex [Zr(CO3)4](4-) were determined. 

PMID- 25384542
TI  - Astigmatism among myopics and its changes from childhood to adult age: a 23-year
      follow-up study.
AB  - PURPOSE: To study the prevalence of and changes in astigmatism from the onset of
      myopia at school age. METHODS: Two hundred and forty myopic schoolchildren (mean
      age 10.9 years), with no previous spectacles, were recruited during 1983-1984 to
      a randomized 3-year clinical trial of bifocal treatment of myopia. Three annual
      examinations with subjective cycloplegic refraction were performed for 237-238
      subjects. Subsequent examinations were performed at the mean ages of 23.2 and
      33.9 years for 178 and 163 subjects, and the last examination, including data
      from prescriptions of different ophthalmologists, for 32 subjects. Corneal
      topography was studied at baseline, at the 3-year follow-up and at the two
      adulthood follow-ups. Prevalence and changes in refractive astigmatism (RA), in
      its polar values J0 and J45, and corneal astigmatism (CA) were studied. RESULTS:
      Mean RA of the right eye increased during follow-up from 0.26 D (SD) +/- 0.30 to
      0.79 D +/- 0.74. Mean CA was 1.07 D +/- 0.74 at study end. The prevalence of RA
      >=0.25 or >=1.00 D increased from 54.9 and 3.8% to 83.4 and 34.4%, respectively.
      The main direction of the axis of RA and its polar value J0 and CA changed mainly
      through sphericity, from against the rule (ATR) to with the rule during the
      follow-up. There was a negative correlation between RA and spherical refraction
      in the ATR group at end of follow-up. Changes in RA were associated with increase
      in myopia and with changes in CA. CONCLUSIONS: The prevalence and mean amount of
      RA associated with CA increased, and the axis of astigmatism changed among
      myopics during the 23-year follow-up.

PMID- 25384543
TI  - PD-1, S-100 and CD1a expression in pseudolymphomatous folliculitis, primary
      cutaneous marginal zone B-cell lymphoma (MALT lymphoma) and cutaneous lymphoid
      hyperplasia.
AB  - BACKGROUND: Pseudolymphomatous folliculitis is a lymphoid proliferation that
      clinically and histopathologically mimics primary cutaneous extranodal marginal
      zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In this
      study, we assessed the diagnostic value of three immunohistochemical markers,
      programmed death-1 (PD-1), CD1a and S100. METHODS: We evaluated 25 cases of
      cutaneous lymphoid proliferations with established diagnoses, including 9
      patients with pseudolymphomatous folliculitis, 11 with MALT lymphoma, and 5 with
      cutaneous lymphoid hyperplasia (CLH). The clinical, histopathologic and
      immunohistochemical characteristics were reviewed and three major characteristics
      assessed: (a) proportion of T cells expressing PD-1, (b) pattern of expression of
      CD1a by dendritic cells and (c) pattern of expression of S100 by dendritic cells.
      RESULTS: We found pseudolymphomatous folliculitis to have a significant increase
      in PD-1+ T cells compared with MALT lymphoma (p < 0.0001). The pattern of CD1a
      staining is also informative: MALT lymphoma is significantly more likely to
      demonstrate a peripheral concentration of CD1a+ dendritic cells around lymphoid
      nodules than pseudolymphomatous folliculitis (p < 0.0003) or CLH (p < 0.05).
      Pseudolymphomatous folliculitis demonstrates an interstitial distribution of
      CD1a+ cells more often than MALT lymphoma (p < 0.04). S100 staining was not a
      helpful discriminator. CONCLUSIONS: Histopathologic factors including PD-1 and
      CD1a staining patterns may allow for more certainty in distinguishing lymphoid
      hyperplasia, including pseudolymphomatous folliculitis, from MALT lymphoma.

PMID- 25384544
TI  - Improving enzymatic hydrolysis of corn stover pretreated by ethylene glycol
      perchloric acid-water mixture.
AB  - To improve the enzymatic saccharification of lignocellulosic biomass, a mixture
      of ethylene glycol-HClO4-water (88.8:1.2:10, w/w/w) was used for pretreating corn
      stover in this study. After the optimization in oil-bath system, the optimum
      pretreatment temperature and time were 130  degrees C and 30 min, respectively.
      After the saccharification of 10 g/L pretreated corn stover for 48 h, the
      saccharification rate was obtained in the yield of 77.4 %. To decrease
      pretreatment temperature and shorten pretreatment time, ethylene glycol-HClO4
      water (88.8:1.2:10, w/w/w) media under microwave irradiation was employed to
      pretreat corn stover effectively at 100  degrees C and 200 W for 5 min. Finally,
      the recovered hydrolyzates containing glucose obtained from the enzymatic
      hydrolysis of pretreated corn stovers could be fermented into ethanol
      efficiently. These results would be helpful for developing a cost-effective
      pretreatment combined with enzymatic saccharification of cellulosic materials for
      the production of lignocellulosic ethanol.

PMID- 25384545
TI  - Recombination of thermo-alkalistable, high xylooligosaccharides producing endo
      xylanase from Thermobifida fusca and expression in Pichia pastoris.
AB  - For xylooligosaccharide (XO) production, endo-xylanase from Thermobifida fusca
      was modified by error-prone PCR and DNA shuffling. The G4SM1 mutant (S62T, S144C,
      N198D, and A217V) showed the most improved hydrolytic activity and was two copies
      expressed in Pichia pastoris under the control of GAP promoter. The maximum
      xylanase activity in culture supernatants was 165 +/- 5.5 U/ml, and the secreted
      protein concentration reached 493 mg/l in a 2-l baffled shake flask. After 6* His
      tagged protein purification, the specific activity of G4SM1 was 2036 +/- 45.8
      U/mg, 2.12 times greater than that of wild-type enzyme. Additionally, G4SM1 was
      stable over a wide pH range from 5.0 to 9.0. Meanwhile, half-life of G4SM1
      thermal inactivation at 70  degrees C increased 8.5-fold. Three-dimensional
      structures suggest that two amino acid substitutions, S62T and S144C, located at
      catalytic domain may be responsible for the enhanced activity and thermostability
      of xylanase. Xylobiose was the dominant end product of xylan hydrolysis by G4SM1.
      Due to its attractive biochemical properties, G4SM1 has potential value in
      commercial XO production.

PMID- 25384546
TI  - Liver, pancreas and kidney transplantation for the treatment of Wolcott-Rallison
      syndrome.
AB  - We present the case of a child who underwent a combined liver, pancreas and
      double kidney transplant following complications of Wolcott-Rallison syndrome
      (WRS) a rare genetic disorder that causes infantile insulin-dependent diabetes
      mellitus (IDDM) and often death in childhood from fulminant liver and concomitant
      kidney failure. WRS is characterized clinically through infantile IDDM,
      propensity for liver failure following viral infections, bone dysplasia and
      growth failure and developmental delay. Fewer than 60 cases with WRS are reported
      in the literature, mostly from consanguineous parents. Future episodes of liver
      failure, the main contributor to the increased mortality in WRS, may be prevented
      through timely liver transplantation. To the best of our knowledge,
      transplantation has not been utilized to manage complications of WRS prior to
      this report.

PMID- 25384547
TI  - Aren't thirty years enough to affirm the full maturity of modern geriatrics?

PMID- 25384548
TI  - Insulin-Like Growth Factor-I, Insulin-Like Growth factor Binding Protein-3 and
      Blood Hemoglobin Concentration in an Elderly Population.
AB  - BACKGROUND: Insulin-like growth factor-I (IGF-I) serum level decreases with age,
      and this decrease may underlie hemoglobin (Hb) decrease. The objective of the
      study was to assess the relationship between IGF-I and insulin-like growth factor
      binding protein-3 (IGFBP-3) serum levels and Hb, after adjustment especially for
      major nutritional factors in an elderly population because IGF-I system depends
      on nutritional state, often impaired in the elderly. METHODS: Hemoglobin
      concentration was tested for 672 participants evaluated during an outpatient
      geriatric assessment. IGF-I and IGFBP-3 serum levels were assessed by Enzyme
      Linked Immunosorbent Assay. The molar ratio of IGF-I/IGFBP-3 that reflects the
      bioavailable IGF-I was calculated. Levels of IGF-I and IGFBP-3 were plotted
      against quartiles of Hb. Final linear models for IGF-I, IGFBP-3 and ratio molar
      included factors that could modify the Hb level. RESULTS: Mean age (SD) of the
      sample was 78.0 (8.5) years old and 32% were men. After adjustment for age and
      sex, IGF-I serum level, IGFBP-3 serum level and molar ratio significantly
      increased with increasing quartiles of Hb. After adjustment for age, gender,
      diabetes, albumin, pre-albumin, renal function, total cholesterol, angiotensin
      converting enzyme inhibitors and angiotensin II receptor blockers consumption, C
      Reactive Protein, Hb was significantly associated and with IGF-I level (p = .002)
      and molar ratio (p = .02). CONCLUSIONS: IGF-I serum level and IGF-I/IGFBP-3 molar
      ratio were associated with Hb in an elderly population, independently of
      nutritional biological parameters. Thus, the association between the IGF-I system
      and Hb merits further investigation to determine whether interventions that
      modulate circulating IGF-I or IGF-I/BP3 ratio might preserve Hb in the elderly.

PMID- 25384549
TI  - NaDC3 Induces Premature Cellular Senescence by Promoting Transport of Krebs Cycle
      Intermediates, Increasing NADH, and Exacerbating Oxidative Damage.
AB  - High-affinity sodium-dependent dicarboxylate cotransporter 3 (NaDC3) is a key
      metabolism-regulating membrane protein responsible for transport of Krebs cycle
      intermediates. NaDC3 is upregulated as organs age, but knowledge regarding the
      underlying mechanisms by which NaDC3 modulates mammalian aging is limited. In
      this study, we showed that NaDC3 overexpression accelerated cellular senescence
      in young human diploid cells (MRC-5 and WI-38) and primary renal tubular cells,
      leading to cell cycle arrest in G1 phase and increased expression of senescent
      biomarkers, senescence-associated beta-galactosidase and p16. Intracellular
      levels of reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, malondialdehyde,
      and carbonyl were significantly enhanced, and activities of respiratory complexes
      I and III and ATP level were significantly decreased in NaDC3-infected cells.
      Stressful premature senescent phenotypes induced by NaDC3 were markedly
      ameliorated via treatment with the antioxidants Tiron and Tempol. High expression
      of NaDC3 caused a prominent increase in intracellular levels of Krebs cycle
      intermediates and NADH. Exogenous NADH and NAD(+) may aggravate and attenuate the
      aging phenotypes induced by NaDC3, respectively. These results suggest that NaDC3
      can induce premature cellular senescence by promoting the transport of Krebs
      cycle intermediates, increasing generation of NADH and reactive oxygen species
      and leading to oxidative damage. Our results clarify the aging signaling pathway
      regulated by NaDC3. 

PMID- 25384550
TI  - Life paths and accomplishments of mathematically precocious males and females
      four decades later.
AB  - Two cohorts of intellectually talented 13-year-olds were identified in the 1970s
      (1972-1974 and 1976-1978) as being in the top 1% of mathematical reasoning
      ability (1,037 males, 613 females). About four decades later, data on their
      careers, accomplishments, psychological well-being, families, and life
      preferences and priorities were collected. Their accomplishments far exceeded
      base-rate expectations: Across the two cohorts, 4.1% had earned tenure at a major
      research university, 2.3% were top executives at "name brand" or Fortune 500
      companies, and 2.4% were attorneys at major firms or organizations; participants
      had published 85 books and 7,572 refereed articles, secured 681 patents, and
      amassed $358 million in grants. For both males and females, mathematical
      precocity early in life predicts later creative contributions and leadership in
      critical occupational roles. On average, males had incomes much greater than
      their spouses', whereas females had incomes slightly lower than their spouses'.
      Salient sex differences that paralleled the differential career outcomes of the
      male and female participants were found in lifestyle preferences and priorities
      and in time allocation. 

PMID- 25384552
TI  - Auditory verbal hallucinations reflect stable auditory attention deficits: a
      prospective study.
AB  - INTRODUCTION: Previous studies have shown that auditory verbal hallucinations
      (AVHs) in psychosis are associated with reduced verbal auditory attention.
      Whether this is an effect of ongoing AVH or reflects a more stable cognitive
      vulnerability also present after treating the AVH is unknown. The aim of this
      study was to follow patients with acute psychosis with and without AVH, and to
      test their auditory attention in a more stabilised clinical phase. METHODS: Fifty
      patients (35 males and 15 females) were examined when admitted to an acute
      psychiatry ward and tested three months later with a dichotic listening test with
      attention instructions. The patients were divided into a frequent (n = 33) and
      non-frequent (n = 17) AVH group based on their score on the Positive and Negative
      Syndrome Scale item hallucinatory behaviour (>=4 and <=3, respectively) at
      baseline. RESULTS: A significant interaction emerged between AVH group and
      attention instruction condition; the frequent AVH group failed to control their
      auditory attention as opposed to the non-frequent AVH group. CONCLUSIONS:
      Patients with frequent AVH in an acute psychotic state showed impaired auditory
      attention three months after their AVH had been treated, indicating a stable
      cognitive vulnerability factor for experiencing AVH.

PMID- 25384551
TI  - Blind insight: metacognitive discrimination despite chance task performance.
AB  - Blindsight and other examples of unconscious knowledge and perception demonstrate
      dissociations between judgment accuracy and metacognition: Studies reveal that
      participants' judgment accuracy can be above chance while their confidence
      ratings fail to discriminate right from wrong answers. Here, we demonstrated the
      opposite dissociation: a reliable relationship between confidence and judgment
      accuracy (demonstrating metacognition) despite judgment accuracy being no better
      than chance. We evaluated the judgments of 450 participants who completed an AGL
      task. For each trial, participants decided whether a stimulus conformed to a
      given set of rules and rated their confidence in that judgment. We identified
      participants who performed at chance on the discrimination task, utilizing a
      subset of their responses, and then assessed the accuracy and the confidence
      accuracy relationship of their remaining responses. Analyses revealed above
      chance metacognition among participants who did not exhibit decision accuracy.
      This important new phenomenon, which we term blind insight, poses critical
      challenges to prevailing models of metacognition grounded in signal detection
      theory. 

PMID- 25384553
TI  - Trauma memories, mental health, and resilience: a prospective study of Afghan
      youth.
AB  - BACKGROUND: Studies of war-affected youth have not yet examined how trauma
      memories relate to prospective changes in mental health and to subjective or
      social experiences. METHODS: We interviewed a gender-balanced, randomly selected
      sample of Afghan child-caregiver dyads (n = 331, two waves, 1 year apart). We
      assessed lifetime trauma with a Traumatic Event Checklist, past-year events with
      a checklist of risk and protective events, and several child mental health
      outcomes including posttraumatic distress (Child Revised Impact of Events Scale,
      CRIES) and depression. We examined the consistency of trauma recall over time,
      identified mental health trajectories with latent transition modeling, and
      assessed the predictors of posttraumatic distress and depression trajectories
      with multinomial logistic regressions. RESULTS: From baseline to follow-up,
      reports of lifetime trauma significantly changed (p <= 0.01). A third of the
      cohort reported no trauma exposure; only 10% identified the same event as their
      most distressing experience. We identified four CRIES trajectories: low or no
      distress (52%), rising distress (15%), declining distress (21%), and sustained
      high distress (12%). Youth with chronic posttraumatic distress were more likely
      to be girls (OR = 5.78, p <= 0.01), report more trauma exposure at baseline (OR =
      1.55, p <= 0.05) and follow-up (OR = 5.96, p <= 0.01), and experience ongoing
      domestic violence (OR = 4.84, p <= 0.01). The risks of rising distress and
      sustained distress showed a steady increase for youth recalling up to four
      traumatic experiences. Depression and CRIES trajectories showed weak comorbidity.
      CONCLUSIONS: Memories of violent events are malleable, embedded in social
      experiences, and present heterogeneous associations with posttraumatic distress.
      Our study provides insights on resilience and vulnerability to multiple adverse
      childhood experiences, highlighting research and clinical implications for
      understanding trauma in conflict-affected youth.

PMID- 25384554
TI  - C-H bond activation by f-block complexes.
AB  - Most homogeneous catalysis relies on the design of metal complexes to trap and
      convert substrates or small molecules to value-added products. Organometallic
      lanthanide compounds first gave a tantalizing glimpse of their potential for
      catalytic C-H bond transformations with the selective cleavage of one C-H bond in
      methane by bis(permethylcyclopentadienyl)lanthanide methyl [(eta(5) -C5 Me5 )2
      Ln(CH3 )] complexes some 25 years ago. Since then, numerous metal complexes from
      across the periodic table have been shown to selectively activate hydrocarbon C-H
      bonds, but the challenges of closing catalytic cycles still remain; many f-block
      complexes show great potential in this important area of chemistry.

PMID- 25384555
TI  - A novel endoscopic submucosal dissection technique for proton pump inhibitor
      refractory gastroesophageal reflux disease.
AB  - OBJECTIVES: Although drug treatment is the usual first-line therapy for
      gastroesophageal reflux disease (GERD), not all patients receive satisfactory
      relief from drug therapy, alone. We developed an endoscopic fundoplication
      technique using endoscopic submucosal dissection (ESD); the technique is referred
      to as ESD for GERD (ESD-G). This study investigated the safety and efficacy of
      this novel technique in patients with drug-refractory GERD. PATIENTS AND METHODS:
      ESD-G narrows the hiatal opening through ESD of the esophagogastric junction
      (EGJ) mucosa. For safety reasons, the range of mucosal resection was limited to
      half (1/2 or 1/4 +1/4) of the circumference of the EGJ lumen. ESD-G was performed
      on 13 patients with proton pump inhibitor (PPI)-refractory GERD. GERD symptoms,
      PPI dose, and 24-h esophageal pH monitoring results were compared before and 6
      months after the procedure. Results. In 12 cases, symptoms significantly improved
      after ESD-G. Five patients demonstrated improved esophagitis, three were able to
      discontinue PPI therapy, and three were able to reduce their PPI dosage following
      surgery. The esophageal pH <4 holding time ratio was also decreased after ESD-G.
      Conclusions. ESD-G may be useful for PPI-refractory GERD patients.

PMID- 25384556
TI  - The self-assembly of anticancer camptothecin-dipeptide nanotubes: a minimalistic
      and high drug loading approach to increased efficacy.
AB  - 20-(S)-Camptothecin (CPT)-conjugated dipeptides are reported that preassemble
      into nanotubes with diameters ranging from 80-120 nm. These nanoassemblies
      maintain a high (~47 %) drug loading and exhibit greater drug stability (i.e.,
      resistance to lactone hydrolysis), and consequently greater efficacy against
      several human cancer cells (HT-29, A549, H460, and H23) in vitro compared with
      the clinically used prodrug irinotecan. A key and defining feature of this system
      is the use of the CPT-conjugated dipeptide as both the drug and precursor to the
      nanostructured carrier, which simplifies the overall fabrication process. 

PMID- 25384557
TI  - A single regulatory gene is sufficient to alter Vibrio aestuarianus pathogenicity
      in oysters.
AB  - Oyster diseases caused by pathogenic vibrios pose a major challenge to the
      sustainability of oyster farming. In France, since 2012 a disease affecting
      specifically adult oysters has been associated with the presence of Vibrio
      aestuarianus. Here, by combining genome comparison, phylogenetic analyses and
      high-throughput infections of strains isolated before or during the recent
      outbreaks, we show that virulent strains cluster into two V. aestuarianus
      lineages independently of the sampling dates. The bacterial lethal dose was not
      different between strains isolated before or after 2012. Hence, the emergence of
      a new highly virulent clonal strain is unlikely. Each lineage comprises nearly
      identical strains, the majority of them being virulent, suggesting that within
      these phylogenetically coherent virulent lineages a few strains have lost their
      pathogenicity. Comparative genomics allowed the identification of a single
      frameshift in a non-virulent strain. This mutation affects the varS gene that
      codes for a signal transduction histidine-protein kinase. Genetic analyses
      confirmed that varS is necessary for infection of oysters and for a secreted
      metalloprotease expression. For the first time in a Vibrio species, we show here
      that VarS is a key factor of pathogenicity. 

PMID- 25384558
TI  - Combined ultrasound and photoacoustic imaging to noninvasively assess burn injury
      and selectively monitor a regenerative tissue-engineered construct.
AB  - Current biomedical imaging tools have limitations in accurate assessment of the
      severity of open and deep burn wounds involving excess bleeding and severe tissue
      damage. Furthermore, sophisticated imaging techniques are needed for advanced
      therapeutic approaches such as noninvasive monitoring of stem cells seeded and
      applied in a biomedical 3D scaffold to enhance wound repair. This work introduces
      a novel application of combined ultrasound (US) and photoacoustic (PA) imaging to
      assess both burn injury and skin tissue regeneration. Tissue structural damage
      and bleeding throughout the epidermis and dermis till the subcutaneous skin layer
      were imaged noninvasively by US/PA imaging. Gold nanoparticle-labeled adipose
      derived stem cells (ASCs) within a PEGylated fibrin 3D gel were implanted in a
      rat model of cutaneous burn injury. ASCs were successfully tracked till 2 weeks
      and were distinguished from host tissue components (e.g., epidermis, fat, and
      blood vessels) through spectroscopic PA imaging. The structure and function of
      blood vessels (vessel density and perfusion) in the wound bed undergoing skin
      tissue regeneration were monitored both qualitatively and semi-quantitatively by
      the developed imaging approach. Imaging-based analysis demonstrated ASC
      localization in the top layer of skin and a higher density of regenerating blood
      vessels in the treated groups. This was corroborated with histological analysis
      showing localization of fluorescently labeled ASCs and smooth muscle alpha actin
      positive blood vessels. Overall, the US/PA imaging-based strategy coupled with
      gold nanoparticles has a great potential for stem cell therapies and tissue
      engineering due to its noninvasiveness, safety, selectivity, and ability to
      provide long-term monitoring. 

PMID- 25384560
TI  - GP in jail for child rape is struck off.

PMID- 25384559
TI  - Airway obstruction, upper airway artifact and response to bronchodilator in
      asthmatic and healthy children.
AB  - BACKGROUND: The forced oscillation technique (FOT) may be affected by the upper
      airway artifact in children with airway obstruction. The aim was to test the
      impact of the artifact on FOT ability to diagnose asthma in children as
      recommended by current guidelines. METHODS: The FOT was performed in 58
      asthmatics and 27 controls before and after salbutamol. Respiratory resistance
      (Rrs) was measured at 8 Hz with a standard generator (SG), and a head generator
      (HG) that minimizes the upper airway artifact. The response to salbutamol was
      computed as change in respiratory resistance (Delta%Rrs) and admittance
      (Delta%Ars) that almost cancels the effect of the upper airway artifact. RESULTS:
      Rrs and Delta%Rrs were significantly larger in patients than controls by HG
      (respectively P < 0.001 and P = 0.002) but not SG, while Delta%Ars was larger in
      asthma than control by both (P < 0.04). Best discriminators between patients and
      controls were Rrs or Delta%Rrs by HG and Delta%Ars by SG. CONCLUSION: In
      asthmatic children, the upper airway artifact significantly impacts FOT
      measurements. The diagnostic value may be improved by minimization of the shunt,
      such as the computation of Delta%Ars.

PMID- 25384561
TI  - Low IL-10/TNFalpha ratio in patients with coronary artery disease and reduced
      left ventricular ejection fraction with a poor prognosis after 10 years.
AB  - Monocytes and dendritic cells (DC) produce tumour necrosis factor (TNF)alpha
      during inflammatory processes, but secrete interleukin (IL)-10 simultaneously in
      order to balance the pro-inflammation. In the present study, we investigated the
      expression of TNFalpha and IL-10 by monocytes and DC in patients with a poor
      cardiovascular prognosis after 10 years. Peripheral blood monocytes were isolated
      from 30 patients with coronary artery disease (CAD) with stable angina pectoris
      (SAP), or with an acute coronary syndrome (ACS). Monocytes were differentiated
      over 7 days to DC. Intracellular accumulation of TNFalpha and IL-10 in monocytes
      and DC was analysed by flow cytometry and correlated with the heart function,
      total and cardiovascular (CV) mortality, as well as with cardiovascular event
      rate over 10 years. We observed a decreased left ventricular function (LV-EF) for
      both SAP and ACS patients (p<0.01), as well as a reduced IL-10/TNFalpha ratio for
      monocytes (p=0.01) and DC (p<0.01) for both patient groups in comparison to age
      matched control group. Only the IL-10/TNFalpha ratio for monocytes correlated
      with LV-EF (r=0.4302; p<0.01). Patients with a low LV-EF as well as patients with
      a low IL-10/TNFalpha ratio showed an increased cardiovascular mortality over 10
      years (both p<0.05). The IL-10/TNFalpha ratio is decreased in patients with low
      ejection fraction and poor prognosis. The reduced heart function correlates with
      an increased proinflammatory state (low monocytic IL-10/TNFalpha ratio) in
      patients with CAD. This observed imbalance of IL-10 and TNFalpha in monocytes
      might explain pathophysiological processes in atherosclerosis and heart failure.

PMID- 25384562
TI  - Overexpression and Potential Regulatory Role of IL-17F in Pathogenesis of Chronic
      Periodontitis.
AB  - The objective of this study was to investigate the expression level, clinical
      significance, and possible regulating role of IL-17F in patients of chronic
      periodontitis. Periodontal local tissues were obtained from chronic periodontitis
      (CP) and healthy controls (HC) for real-time PCR (RT-PCR) detection with IL-17F
      and IL-17A messenger RNA (mRNA). Primary human gingival fibroblasts (HGF) were
      derived from patients receiving crown-lengthening procedures. Efficiency of small
      interfering RNA (siRNA) of IL-17R to HGF cells were assessed by Western blot and
      RT-PCR. Recombinant IL-17F and IL-17A were used to stimulate the HGF cells
      compared with the control group. Aspects of the nuclear factor-kappa B (NF
      kappaB) and extracellular signal-regulated kinase (ERK) signaling pathways were
      examined by Western blot. Production of pro-inflammatory cytokines induced by IL
      17F and IL-17A was detected by RT-PCR. Statistical analysis was analyzed by SPSS
      software. It showed significantly elevated levels of IL-17F and IL-17A mRNA in CP
      gingival tissues compared with HC group (P<0.01). Further analysis showed a
      significant correlation between IL-17F and IL-17A mRNA in CP group (P<0.05), and
      both cytokines also correlated with the probing depth (P<0.05). Recombinant IL
      17F can induce NF-kappaB phosphor-p65 and ERK phosphorylation of HGF cells
      similar to that of IL-17A. Interestingly, we found that both IL-17F and IL-17A
      could promote the important inflammatory cytokines IL-6, CXCL8, and CCL20
      production compared with IL-17R siRNA group (P<0.05). This study indicates that
      IL-17F may be involved in pathogenesis of periodontitis like IL-17A. The role of
      IL-17F in disease pathogenesis needs to be further investigated.

PMID- 25384564
TI  - Commentary on lopez-munoz and alamo.

PMID- 25384563
TI  - Automated update, revision, and quality control of the maize genome annotations
      using MAKER-P improves the B73 RefGen_v3 gene models and identifies new genes.
AB  - The large size and relative complexity of many plant genomes make creation,
      quality control, and dissemination of high-quality gene structure annotations
      challenging. In response, we have developed MAKER-P, a fast and easy-to-use
      genome annotation engine for plants. Here, we report the use of MAKER-P to update
      and revise the maize (Zea mays) B73 RefGen_v3 annotation build (5b+) in less than
      3 h using the iPlant Cyberinfrastructure. MAKER-P identified and annotated 4,466
      additional, well-supported protein-coding genes not present in the 5b+ annotation
      build, added additional untranslated regions to 1,393 5b+ gene models, identified
      2,647 5b+ gene models that lack any supporting evidence (despite the use of large
      and diverse evidence data sets), identified 104,215 pseudogene fragments, and
      created an additional 2,522 noncoding gene annotations. We also describe a method
      for de novo training of MAKER-P for the annotation of newly sequenced grass
      genomes. Collectively, these results lead to the 6a maize genome annotation and
      demonstrate the utility of MAKER-P for rapid annotation, management, and quality
      control of grasses and other difficult-to-annotate plant genomes. 

PMID- 25384565
TI  - Rey Visual Design Learning Test performance correlates with white matter
      structure.
AB  - OBJECTIVE: Studies exploring relation of visual memory to white matter are
      extensively lacking. The Rey Visual Design Learning Test (RVDLT) is an elementary
      motion, colour and word independent visual memory test. It avoids a significant
      contribution from as many additional higher order visual brain functions as
      possible to visual performance, such as three-dimensional, colour, motion or word
      dependent brain operations. Based on previous results, we hypothesised that test
      performance would be related with white matter of dorsal hippocampal commissure,
      corpus callosum, posterior cingulate, superior longitudinal fascicle and internal
      capsule. METHODS: In 14 healthy subjects, we measured intervoxel coherence (IC)
      by diffusion tensor imaging as an indication of connectivity and visual memory
      performance measured by the RVDLT. IC considers the orientation of the adjacent
      voxels and has a better signal-to-noise ratio than the commonly used fractional
      anisotropy index. RESULTS: Using voxelwise linear regression analyses of the IC
      values, we found a significant and direct relationship between 11 clusters and
      visual memory test performance. The fact that memory performance correlated with
      white matter structure in left and right dorsal hippocampal commissure, left and
      right posterior cingulate, right callosal splenium, left and right superior
      longitudinal fascicle, right medial orbitofrontal region, left anterior
      cingulate, and left and right anterior limb of internal capsule emphasises our
      hypothesis. CONCLUSION: Our observations in healthy subjects suggest that
      individual differences in brain function related to the performance of a task of
      higher cognitive demands might partially be associated with structural variation
      of white matter regions.

PMID- 25384566
TI  - Visuospatial encoding deficits and compensatory strategies in schizophrenia
      revealed by eye movement analysis during a working memory task.
AB  - OBJECTIVE: To investigate scanpath abnormalities during the encoding of static
      stimuli in schizophrenia and their interaction with visuospatial working memory
      (VSWM) dysfunction. METHODS: Outpatients with schizophrenia and control subjects
      were asked to encode a static pattern for subsequent recognition after a short
      delay. We measured the number of correct and incorrect choices. We also assessed
      the number and the distribution of fixations, the scanning time in specific
      regions of interest (ROIs) and the head movements during the encoding of the
      stimuli. The distributions of fixations and scanning time in definite ROIs during
      the discrimination of the correct pattern from the foils were also measured.
      RESULTS: Patients recognised fewer correct patterns than controls. Correct trials
      in patients were characterised by a specific exploration of the central part of
      the stimulus during its presentation, whereas this feature was absent in
      incorrect trials. However, the scanning time and the numbers of fixations and
      head movements during encoding were similar in both groups and unrelated to
      recognition accuracy. In both groups, correct trials were associated with a
      selective exploration of the correct pattern amongst the six possibilities during
      recognition. Furthermore, patients gave more attention to incorrect patterns with
      a leftmost element identical to that of the correct response and also those
      approximating its global structure. CONCLUSION: Patients showed a VSWM deficit
      independent of oculomotor dysfunctions and head movements during encoding.
      Patients' correct trials were related to specific scanning during encoding and
      discrimination phases. Analysis of these patterns suggests that patients try to
      compensate for reduced VSWM ability by using specific encoding strategies.

PMID- 25384567
TI  - Obesity and metabolic syndrome in Brazilian patients with bipolar disorder.
AB  - OBJECTIVE: We aimed to determine the prevalence of obesity and metabolic syndrome
      (O/MetS) in a sample of Brazilian outpatients with bipolar disorder. METHODS:
      Eighty-four patients with bipolar disorder were evaluated. We used the definition
      of MetS established in the Third Report of the National Cholesterol Education
      Program Expert Panel on Detection, Evaluation and Treatment of High Blood
      Cholesterol in Adults, modified by the American Heart Association (AHA). Patients
      were classified as obese if their body mass index (BMI) was >= 30 kg/m2. RESULTS:
      We found that 28.6% of our sample met the AHA criteria for MetS and 35.7% were
      obese. The percentage of patients meeting each criterion of the AHA was as
      follows: 46% for abdominal obesity; 44% for hypertriglyceridemia or cholesterol
      lowering medication use; 26% for low high-density lipoprotein cholesterol or
      being on a lipid-lowering medication; 45% for hypertension; and 20% for high
      fasting glucose or anti-diabetic medication use. CONCLUSIONS: The prevalence of
      obesity in our sample of outpatients with bipolar disorder was higher than that
      observed for the general population of Brazil. The rate of MetS was similar to
      that observed for the general population. Our data indicate the need for
      prevention, early detection and treatment of O/MetS in patients with bipolar
      disorder.

PMID- 25384569
TI  - Evaluation of melatonin treatment in primary culture of canine mammary tumors.
AB  - Mammary neoplasias are the most common tumors observed in female dogs.
      Identification of these tumors is valuable in order to identify beneficial
      therapeutic agents as alternative treatments for this tumor type. Oral
      administration of melatonin appears to exert an oncostatic effect on mammary
      neoplasia and may have a possible mechanism of action through its interaction
      with estrogen receptors on epithelial cells. Hence, we analyzed the potential
      therapeutic value of melatonin in tumors that are estrogen-dependent or 
      independent, and established a relationship of its action with the expression of
      the melatonin receptors MT1 and MT2. Furthermore, we analyzed the rate of cell
      proliferation and apoptosis after treatment with melatonin. Cell cultures were
      performed using 10 canine mammary tumor fragments and were divided into estrogen
      receptor (ER)-positive and ER-negative tumors. The results showed that both ER
      positive and ER-negative tumors had decreased cell viability and proliferation
      after treatment with melatonin (p<0.05), although treatment was more effective in
      the ER-positive tumors. Analysis of the relative expression of the MT1 and MT2
      genes by quantitative PCR was performed and the data were compared with the
      expression of ER in 24 canine mammary tumors and the cellular response to
      melatonin in 10 samples. MT1 was overexpressed in ER-positive tumors (p<0.05),
      whereas MT2 was not expressed. Furthermore, melatonin treatment in ER-positive
      tumors showed an efficient oncostatic effect by inhibiting cell viability and
      proliferation and inducing apoptosis. These results suggest that melatonin
      decreased neoplastic mammary cell proliferation and viability and induced
      apoptosis, with greater efficacy in ER-positive tumors that have a high
      expression of melatonin receptor MT1. This is a strong evidence for the use of
      melatonin as a therapeutic agent for estrogen-dependent canine mammary tumors.

PMID- 25384568
TI  - Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene
      cluster may underlie cognitive deficits rescued by nicotine in transgenic mice.
AB  - Addiction involves long-lasting maladaptive changes including development of
      disruptive drug-stimuli associations. Nicotine-induced neuroplasticity underlies
      the development of tobacco addiction but also, in regions such as the
      hippocampus, the ability of this drug to enhance cognitive capabilities. Here, we
      propose that the genetic locus of susceptibility to nicotine addiction, the
      CHRNA5/A3/B4 gene cluster, encoding the alpha5, alpha3 and beta4 subunits of the
      nicotinic acetylcholine receptors (nAChRs), may influence nicotine-induced
      neuroadaptations. We have used transgenic mice overexpressing the human cluster
      (TgCHRNA5/A3/B4) to investigate hippocampal structure and function in genetically
      susceptible individuals. TgCHRNA5/A3/B4 mice presented a marked reduction in the
      dendrite complexity of CA1 hippocampal pyramidal neurons along with an increased
      dendritic spine density. In addition, TgCHRNA5/A3/B4 exhibited increased
      VGLUT1/VGAT ratio in the CA1 region, suggesting an excitatory/inhibitory
      imbalance. These hippocampal alterations were accompanied by a significant
      impairment in short-term novelty recognition memory. Interestingly, chronic
      infusion of nicotine (3.25 mg/kg/d for 7 d) was able to rescue the reduced
      dendritic complexity, the excitatory/inhibitory imbalance and the cognitive
      impairment in TgCHRNA5/A3/B4. Our results suggest that chronic nicotine treatment
      may represent a compensatory strategy in individuals with altered expression of
      the CHRNA5/A3/B4 region. 

PMID- 25384571
TI  - Modulation of Caenorhabditis elegans immune response and modification of Shigella
      endotoxin upon interaction.
AB  - To analyze the pathogenesis at both physiological and molecular level using the
      model organism, Caenorhabditis elegans at different developmental stages in
      response to Shigella spp. and its pathogen associated molecular patterns such as
      lipopolysaccharide. The solid plate and liquid culture-based infection assays
      revealed that Shigella spp. infects C. elegans and had an impact on the brood
      size and pharyngeal pumping rate. LPS of Shigella spp. was toxic to C. elegans.
      qPCR analysis revealed that host innate immune genes have been modulated upon
      Shigella spp. infections and its LPS challenges. Non-destructive analysis was
      performed to kinetically assess the alterations in LPS during interaction of
      Shigella spp. with C. elegans. The modulation of innate immune genes attributed
      the surrendering of host immune system to Shigella spp. by favoring the
      infection. LPS appeared to have a major role in Shigella-mediated pathogenesis
      and Shigella employs a tactic behavior of modifying its LPS content to escape
      from the recognition of host immune system. 

PMID- 25384570
TI  - Outcomes of androgen replacement therapy in adult male hypogonadism:
      recommendations from the Italian society of endocrinology.
AB  - OBJECTIVE: We developed clinical practice guidelines to assess the individual
      risk-benefit profile of androgen replacement therapy in adult male hypogonadism
      (HG), defined by the presence of specific signs and symptoms and serum
      testosterone (T) below 12 nmol/L. PARTICIPANTS: The task force consisted of eight
      clinicians experienced in treating HG, selected by the Italian Society of
      Endocrinology (SIE). The authors received no corporate funding or remuneration.
      CONSENSUS PROCESS: Consensus was guided by a systematic review of controlled
      trials conducted on men with a mean T < 12 nmol/L and by interactive discussions.
      The guidelines were reviewed and sequentially approved by the SIE Guidelines
      Commission and Executive Committee. CONCLUSIONS: We recommend T supplementation
      (TS) for adult men with severely reduced T levels (T < 8 nmol/L) to improve body
      composition and sexual function. We suggest that TS be offered to subjects with T
      < 12 nmol/L to improve glycaemic control, lipid profile, sexual function, bone
      mineral density, muscle mass and depressive symptoms, once major
      contraindications have been ruled out. We suggest that lifestyle changes and
      other available interventions (e.g. for erectile dysfunction) be suggested prior
      to TS. We suggest that TS should be combined with currently available treatments
      for individuals at high risk for complications, such as those with osteoporosis
      and/or metabolic disorders. We recommend against using TS to improve cardiac
      outcome and limited mobility. We recommend against using TS in men with prostate
      cancer, unstable cardiovascular conditions or elevated haematocrit. The task
      force places a high value on the timely treatment of younger and middle-aged
      subjects to prevent the long-term consequences of hypoandrogenism.

PMID- 25384572
TI  - Effect of physiological stress on expression of glucose transporter 2 in liver of
      the wood frog, Rana sylvatica.
AB  - Glucose transporters (GLUTs) have been implicated in the survival of various
      physiological stresses in mammals; however, little is known about the role of
      these proteins in stress tolerance in lower vertebrates. The wood frog (Rana
      sylvatica), which survives multiple winter-related stresses by copiously
      mobilizing hepatic glycogen stores, is an interesting subject for the study of
      glucose transport in amphibians. We examined the effects of several physiological
      stresses on GLUT2 protein and mRNA levels in the liver of R. sylvatica. Using
      immunoblotting techniques to measure relative GLUT2 abundance, we found that
      GLUT2 numbers increased in response to organismal freezing, hypoxia exposure, and
      glucose loading; whereas, experimental dehydration and urea loading did not
      affect GLUT2 abundance. GLUT2 mRNA levels, assessed using quantitative real-time
      polymerase chain reaction, changed in accordance with protein abundance for most
      stresses, indicating that transcriptional regulation of GLUT2 occurs in response
      to stress. Overall, hepatic GLUT2 seems to be important in stress survival in R.
      sylvatica and is regulated to meet the physiological need to accumulate glucose.

PMID- 25384573
TI  - High-pressure radiative conductivity of dense silicate glasses with potential
      implications for dark magmas.
AB  - The possible presence of dense magmas at Earth's core-mantle boundary is expected
      to substantially affect the dynamics and thermal evolution of Earth's interior.
      However, the thermal transport properties of silicate melts under relevant high
      pressure conditions are poorly understood. Here we report in situ high-pressure
      optical absorption and synchrotron Mossbauer spectroscopic measurements of iron
      enriched dense silicate glasses, as laboratory analogues for dense magmas, up to
      pressures of 85 GPa. Our results reveal a significant increase in absorption
      coefficients, by almost one order of magnitude with increasing pressure to ~50
      GPa, most likely owing to gradual changes in electronic structure. This suggests
      that the radiative thermal conductivity of dense silicate melts may decrease with
      pressure and so may be significantly smaller than previously expected under core
      mantle boundary conditions. Such dark magmas heterogeneously distributed in the
      lower mantle would result in significant lateral heterogeneity of heat flux
      through the core-mantle boundary. 

PMID- 25384575
TI  - The electron depolarization during dynamic nuclear polarization: measurements and
      simulations.
AB  - Dynamic nuclear polarization is typically explained either using microscopic
      systems, such as in the solid effect and cross effect mechanisms, or using the
      macroscopic formalism of spin temperature which assumes that the state of the
      electrons can be described using temperature coefficients, giving rise to the
      thermal mixing mechanism. The distinction between these mechanisms is typically
      made by measuring the DNP spectrum - i.e. the nuclear enhancement profile as a
      function of irradiation frequency. In particular, we have previously used the
      solid effect and cross effect mechanisms to explain temperature dependent DNP
      spectra. Our past analysis has however neglected the effect of depolarization of
      the electrons resulting from the microwave (MW) irradiation. In this work we
      concentrate on this electron depolarization process and perform electron-electron
      double resonance (ELDOR) experiments on TEMPOL and trityl frozen solutions, using
      a 3.34 Tesla magnet and at 2.7-30 K, in order to measure the state of the
      electron polarization during DNP. The experiments indicate that a significant
      part of the EPR line is affected by the irradiation due to spectral diffusion.
      Using a theoretical framework based on rate equations for the polarizations of
      the different electron spin packets and for those of the nuclei we simulated the
      various ELDOR line-shapes and reproduced the MW frequency and irradiation time
      dependence. The obtained electron polarization distribution cannot be described
      using temperature coefficients as required by the classical thermal mixing
      mechanism, and therefore the DNP mechanism cannot be described by thermal mixing.
      Instead, the theoretical framework presented here for the analysis of the ELDOR
      data forms a basis for future interpretation of DNP spectra in combination with
      EPR measurements. 

PMID- 25384574
TI  - Quality control metrics improve repeatability and reproducibility of single
      nucleotide variants derived from whole-genome sequencing.
AB  - Although many quality control (QC) methods have been developed to improve the
      quality of single-nucleotide variants (SNVs) in SNV-calling, QC methods for use
      subsequent to single-nucleotide polymorphism-calling have not been reported. We
      developed five QC metrics to improve the quality of SNVs using the whole-genome
      sequencing data of a monozygotic twin pair from the Korean Personal Genome
      Project. The QC metrics improved both repeatability between the monozygotic twin
      pair and reproducibility between SNV-calling pipelines. We demonstrated the QC
      metrics improve reproducibility of SNVs derived from not only whole-genome
      sequencing data but also whole-exome-sequencing data. The QC metrics are
      calculated based on the reference genome used in the alignment without accessing
      the raw and intermediate data or knowing the SNV-calling details. Therefore, the
      QC metrics can be easily adopted in downstream association analysis. 

PMID- 25384576
TI  - Microanatomy of the tympanic membrane in chronic myringitis obtained with optical
      coherence tomography.
AB  - A microscope-based optical coherence tomography (OCT) device was used to assess
      the microanatomy of the tympanic membrane in patients with chronic myringitis. A
      prospective study was designed for this purpose. OCT measurements of the tympanic
      membrane were done on 11 patients with myringitis with a microscope-based
      spectral domain OCT system. The in vivo findings were compared with those
      findings of a control group consisting of 36 patients with retraction pockets or
      atrophic tympanic membranes (n = 13), myringosclerosis (n = 12) and perforations
      (n = 11). In active chronic myringitis, the thickness of the tympanic membrane is
      increased compared to healthy membranes and to other pathological conditions of
      the tympanic membrane. Consistent changes of the microanatomy of the tympanic
      membrane were found in chronic myringitis with OCT. Serial OCT measurements
      revealed no biofilm suspicious findings in all patients with active chronic
      myringitis. Intraoperative and in vivo OCT measurements may help to detect
      microanatomical changes of the tympanic membrane in chronic myringitis and in
      other conditions of the tympanic membrane.

PMID- 25384577
TI  - Clinical heterogeneity in progressive supranuclear palsy: challenges to
      diagnosis, pathogenesis and future therapies.

PMID- 25384578
TI  - Determinants of diet for urban aboriginal youth: implications for health
      promotion.
AB  - Overweight and obesity are associated with several life-threating comorbidities,
      including type 2 diabetes and cardiovascular disease. Obesity is a growing health
      concern in North America, with some groups experiencing higher levels of obesity
      than others. One group of particular interest is urban Aboriginal youth because
      they are a quickly growing population who experience high rates of obesity.
      Obesity is a complex condition with many contributing factors, diet being one of
      the primary contributors. In this article, we discuss the findings from an
      ethnographic study that examined determinants of diet for urban Aboriginal youth.
      Results revealed two themes: (a) Traditions and Sharing, and (b) The Struggle.
      The findings with Traditions and Sharing showed that food-sharing networks are
      often used to acquire traditional food. Traditional foods were believed to be
      healthy and desired by the participants. The theme The Struggle provides insight
      into the daily challenges the participants faced with food insecurity. Health
      promotion professionals need to consider the multiplicity of determinants of diet
      for urban Aboriginal youth in order to plan and implement culturally appropriate
      health promotion programs. 

PMID- 25384579
TI  - Improvements in Cardiometabolic Risk Factors Among Overweight and Obese Employees
      Participating in a University Worksite Wellness Program.
AB  - OBJECTIVE: To determine immediate changes in weight and cardiometabolic risk of
      participants in a university worksite wellness program (WWP). It was hypothesized
      that there would be significant improvements in weight and waist circumference
      after 12 weeks. METHOD: Employees volunteered for enrollment in a 12-week WWP
      that provided educational sessions in-person or online. At baseline and after 12
      weeks, participants had one-on-one appointments with the study registered
      dietitian who measured clinical outcome markers (cardiometabolic risk factors)
      and provided individualized counseling. RESULTS: Among 79 participants who
      returned for 12-week appointments, there were statistically significant
      improvements in weight (p < .0001), waist circumference (p < .0001), and other
      cardiometabolic risk factors from baseline to 12-weeks. CONCLUSIONS: Improvements
      in cardiometabolic risk factors may be observed in a relatively short period of
      time among those who enrolled in a WWP.

PMID- 25384580
TI  - Internal Structure Analysis of a Tobacco Control Network on the U.S.-Mexico
      Border.
AB  - Tobacco control (TC) networks (in which multiple agencies collaborate) are
      essential components within comprehensive TC efforts. The aim of this study was
      to assess the internal coalition outcomes hierarchy model (via the Internal
      Coalition Effectiveness [ICE] scale) in the present sample. Participants (members
      of a TC Network on the U.S.-Mexico border; independent Waves 1 [N = 30] and 2 [N
      = 33; at a 1-year subsequent assessment]) completed a background questionnaire
      and an adapted version of the ICE scale. Mean values for ICE subscales suggested
      a strong enthusiasm of Network members and recognition of the importance of a
      cohesive social vision, employment of efficient practices, a need for improved
      and maintained knowledge/training, and stable social relationships among members.
      However, no significant differences were observed between data waves in the ICE
      subscales, multivariate analysis of variance: lambda = .97, F(4, 43) = 0.31, p >
      .86. Considering a multifaceted assessment may enhance the understanding of the
      dynamics and strengths of the Network. Finally, including an assessment of the
      leadership's perspective regarding internal coalition outcome hierarchy model
      constructs to compare them with members' perspective is warranted. 

PMID- 25384582
TI  - Amphibian skull evolution: The developmental and functional context of
      simplification, bone loss and heterotopy.
AB  - Despite their divergent morphology, extant and extinct amphibians share numerous
      features in the timing and spatial patterning of dermal skull elements. Here, I
      show how the study of these features leads to a deeper understanding of
      morphological evolution. Batrachians (salamanders and frogs) have simplified
      skulls, with dermal bones appearing rudimentary compared with fossil tetrapods,
      and open cheeks resulting from the absence of other bones. The batrachian skull
      bones may be derived from those of temnospondyls by truncation of the
      developmental trajectory. The squamosal, quadratojugal, parietal, prefrontal,
      parasphenoid, palatine, and pterygoid form rudimentary versions of their homologs
      in temnospondyls. In addition, failure to ossify and early fusion of bone
      primordia both result in the absence of further bones that were consistently
      present in Paleozoic tetrapods. Here, I propose a new hypothesis explaining the
      observed patterns of bone loss and emargination in a functional context. The
      starting observation is that jaw-closing muscles are arranged in a different way
      than in ancestors from the earliest ontogenetic stage onwards, with muscles
      attaching to the dorsal side of the frontal, parietal, and squamosal. The
      postparietal and supratemporal start to ossify in a similar way as in
      branchiosaurids, but are fused to neighboring elements to form continuous
      attachment areas for the internal adductor. The postfrontal, postorbital, and
      jugal fail to ossify, as their position is inconsistent with the novel
      arrangement of adductor muscles. Thus, rearrangement of adductors forms the
      common theme behind cranial simplification, driven by an evolutionary flattening
      of the skull in the batrachian stem. J. Exp. Zool. (Mol. Dev. Evol.) 9999B: XX
      XX, 2014. (c) 2014 Wiley Periodicals, Inc.

PMID- 25384581
TI  - Sleep apnea is not associated with worse outcomes in kidney transplant
      recipients.
AB  - Obstructive sleep apnea(OSA) is one of the most common sleep disorders in kidney
      transplant recipients, however its long-term consequences have only rarely been
      investigated. Here, we hypothesized that the presence of OSA would be associated
      with higher risk of mortality and faster decline of graft function in kidney
      transplant recipients. In a prospective cohort study 100 prevalent kidney
      transplant recipients who underwent one-night polysomnography at baseline and
      were followed for a median 75 months. Generalized linear mixed-effects models and
      Cox regression models were used to assess the association between OSA and the
      rate of progression of chronic kidney disease(CKD) and mortality. The estimated
      slopes of estimated glomerular filtration rate(eGFR) in patients with and without
      OSA were compared using a two-stage model of eGFR change including only OSA as a
      variable. In this model patients with OSA (eGFR versus time was -0.93 ml/min/1.73
      m(2)/yr(95%CI:-1.75 to-0.11) had a similar slope as compared to patients without
      OSA(eGFR versus time was -1.24 ml/min/1.73 m(2)/yr(95%CI: -1.67 to -0.81). In
      unadjusted Cox proportional regression analyses OSA was not associated with
      higher all-cause mortality risk (Hazard Ratio(HR) = 1.20; 95% Confidence
      Interval(CI): 0.50-2.85). No association was found between the presence of OSA
      and the rate of progression of CKD or all-cause mortality in prevalent kidney
      transplant recipients.

PMID- 25384583
TI  - Resveratrol abrogates the effects of hypoxia on cell proliferation, invasion and
      EMT in osteosarcoma cells through downregulation of the HIF-1alpha protein.
AB  - Resveratrol has been shown to have antineoplastic effects in vivo and in vitro.
      However, the effect of resveratrol on the hypoxia-enhanced proliferation and
      invasion of osteosarcoma cells remains unclear. In this study, we investigated
      the role of resveratrol on regulating proliferation and invasion of osteosarcoma
      cells under hypoxic conditions. Saos-2 cells were cultured under controlled
      hypoxic conditions (3% O2) or normoxic conditions. Resveratrol (50 uM) was added
      in the medium, and hypoxia inducible factor-1alpha (HIF-1alpha) siRNA was used to
      inhibit HIF-1alpha transcription. Proliferation of Saos-2 cells was evaluated by
      the methabenzthiazuron (MTT) assay. The invasive ability of Saos-2 cells was
      determined by a Transwell assay. HIF-1alpha, E-cadherin and vimentin protein
      levels were detected by western blot analysis. HIF-1alpha, E-cadherin and
      vimentin mRNA levels were assessed by RT-PCR. Compared to the control group,
      hypoxia significantly increased the proliferation rate and invasive ability of
      Saos-2 cells. Moreover, hypoxia markedly increased the E-cadherin level and
      decreased vimentin expression. However, resveratrol or HIF-1alpha silencing
      reverted all the above effects of hypoxia in Saos-2 cells. Moreover, resveratrol
      inhibited HIF-1alpha protein accumulation without affecting the HIF-1alpha mRNA
      level. These data suggest that resveratrol can inhibit the hypoxia-enhanced
      proliferation, invasion and epithelial to mesenchymal transition process in
      osteosarcoma via downregulation of the HIF-1alpha protein. Thus, HIF-1alpha may
      be a promising drug target of resveratrol in the context of development of
      anticancer therapy for human osteosarcoma.

PMID- 25384585
TI  - In vitro antioxidant profiling of seabuckthorn varieties and their adaptogenic
      response to high altitude-induced stress.
AB  - In the past few years, seabuckthorn plants have gained special attention due to
      their ability to grow in the harshest of the environment. This adaptability may
      be contributed by various antioxidants present in the plants besides other
      morphological adaptation. As in vivo studies cannot be justified without in vitro
      studies, the present investigation carried out evaluation of both in vitro and in
      vivo antioxidant potentials of aqueous and alcoholic extracts of the leaves of
      Hippophae salicifolia (HS) and Hippophae rhamnoides mongolica (HRM) in comparison
      with Hippophae rhamnoides turkestanica (HRT). The results had clearly depicted
      that in vitro antioxidant potential of the extracts was responsible for the in
      vivo adaptogenic performance in animals during cold and hypoxia exposure under
      restraint stress. Total phenolic content (TPC), total flavonoid content (TFC),
      total protein content, and antioxidant potential were determined. For adaptogenic
      studies, rats with oral drug supplementation were exposed to Cold-hypoxia
      restraint (C-H-R) stresses-induced hypothermia, as a measure of endurance.
      Aqueous extracts of HS showed maximum (99 %) resistance compared to HRT (81 %)
      and HRM (29 %). The levels of biochemical parameters such as malondialdehyde
      (MDA), reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide
      dismutase (SOD), glutathione (GSH/GSSG), and catalase (CAT) in blood samples also
      revealed that the aqueous leaf extract of HS has better antioxidant and
      adaptogenic potential compared to HRM.

PMID- 25384584
TI  - 6,7-di-O-acetylsinococuline (FK-3000) induces G2/M phase arrest in breast
      carcinomas through p38 MAPK phosphorylation and CDC25B dephosphorylation.
AB  - We evaluated the cytostatic effect of 6,7-di-O-acetyl-sinococuline (FK-3000)
      isolated from Stephania delavayi Diels. against breast carcinoma cell lines MDA
      MB-231 and MCF-7. FK-3000 suppressed CDC25B phosphorylation directly and
      indirectly via p38 MAPK phosphorylation. CDC25B dephosphorylation decreased
      levels of cyclin B and phospho-CDC-2, and ultimately induced cell cycle arrest at
      the G2/M phase. The p38 MAPK inhibitor, SB 239063 blocked FK-3000-induced p38
      MAPK phosphorylation and nuclear accumulation, but did not completely rescue cell
      death. Conclusively FK-3000 exerts its antiproliferative effect through two
      pathways: i) G2/M cell cycle arrest via downregulation of cyclin B and phospho
      CDC2 by p38 MAPK phosphorylation and CDC25B dephosphorylation, and ii) p38 MAPK
      independent induction of apoptosis.

PMID- 25384586
TI  - Cancer diagnosis by breath analysis: what is the future?

PMID- 25384587
TI  - Quantitative immunocapture MS: current status and challenges in drug discovery.

PMID- 25384588
TI  - Simultaneous determination of ornidazole and its main metabolites in human plasma
      by LC-MS/MS: application to a pharmacokinetic study.
AB  - BACKGROUND: Ornidazole is a 5-nitroimidazole antimicrobial agent used for almost
      40 years. A novel LC-MS/MS assay was developed and validated for the simultaneous
      determination of ornidazole and its main metabolites (M3, M6, M16-1, and M16-2)
      in human plasma. RESULTS: After extraction from 100 MUl of plasma by protein
      precipitation with acetonitrile, all the analytes were separated on a Capcell PAK
      MG C18 column (100 * 4.6 mm, 5 MUm) within 5.0 min and detected by ESI-MS/MS in
      the positive mode. The validation results met the acceptance criteria as per the
      US FDA and EMA guidelines. CONCLUSION: The validated method was successfully
      applied to a pharmacokinetic study after oral administration of 1000 mg
      ornidazole to six healthy Chinese volunteers.

PMID- 25384589
TI  - A high-throughput LC-MS/MS assay for quantification of artesunate and its
      metabolite dihydroartemisinin in human plasma and saliva.
AB  - AIM: Saliva is an alternative sampling matrix to plasma, offering a noninvasive
      technique, but requires a highly sensitive bioanalytical method. MATERIALS &
      METHODS: An API 3000 triple quadrupole mass spectrometer with an electrospray
      ionization source operated in the positive ion mode was used for the analysis.
      RESULTS: A high-throughput LC-MS/MS method using SPE for the quantification of
      artesunate and dihydroartemisinin in plasma and saliva has been optimized and
      validated according to US FDA guidelines. For both analytes the LLOQ was
      determined to 5 ng/ml and the calibration range was 5-1000 ng/ml for artesunate
      and 5-2000 ng/ml for dihydroartemisinin. CONCLUSION: For the first time, a
      bioanalytical method for determination of artesunate and dihydroartemisinin in
      human saliva has been described, showing possible applicability in clinical
      saliva samples in addition to plasma samples.

PMID- 25384590
TI  - Development and validation of an LC-MS/MS assay for the quantitation of a
      PEGylated anti-CD28 domain antibody in human serum: overcoming interference from
      antidrug antibodies and soluble target.
AB  - AIM: To support drug development of a PEGylated anti-CD28 domain antibody, a
      sensitive and robust LC-MS/MS assay was developed for the first in-human multiple
      ascending dose study. MATERIALS & METHODS: The procedure consists of a protein
      precipitation with acidified acetonitrile, followed by trypsin digestion of the
      supernatant. A surrogate peptide from the complementarity determining region was
      quantified with an LC-MS/MS assay using a stable isotope-labeled internal
      standard with flanking amino acids. An acid dissociation step was found to be
      essential to achieve full analyte recovery in the presence of antidrug antibodies
      and soluble target CD28. RESULTS & CONCLUSION: The fully validated LC-MS/MS assay
      demonstrates good accuracy (% deviation <=6.3) and precision (%CV <=5.2) with an
      lower limit of quantitation of 10 ng/ml.

PMID- 25384591
TI  - Recommendations on incurred sample stability (ISS) by GCC.
AB  - The topic of incurred sample stability (ISS) has generated considerable
      discussion within the bioanalytical community in recent years. The subject was an
      integral part of the seventh annual Workshop on Recent Issues in Bioanalysis
      (WRIB) held in Long Beach, CA, USA, in April 2013, and at the Global CRO Council
      for Bioanalysis (GCC) meeting preceding it. Discussion at both events focused on
      the use of incurred samples for ISS purposes in light of results from a recent
      GCC survey completed by member companies. This paper reports the consensus
      resulting from these discussions and serves as a useful reference for depicting
      ISS issues and concerns, summarizing the GCC survey results and providing helpful
      recommendations on ISS in the context of bioanalytical method development and
      application. 

PMID- 25384592
TI  - Mass spectrometry - an alternative in growth hormone measurement.
AB  - Growth hormone (GH) constitutes a set of closely related protein isoforms. In
      clinical practice, the disagreement of test results between commercially
      available ligand-binding assays is still an ongoing issue, and incomplete
      knowledge about the particular function of the different forms leaves an
      uncertainty of what should be the appropriate measurand. Mass spectrometry is
      promising to be a way forward. Not only is it capable of providing SI-traceable
      reference values for the calibration of current GH-tests, but it also offers an
      independent approach to highly reliable mass-selective quantification of
      individual GH-isoforms. This capability may add to reliability in doping control
      too. The article points out why and how. 

PMID- 25384593
TI  - Large-scale label-free phosphoproteomics: from technology to data interpretation.
AB  - Protein phosphorylation plays a central role in the dynamic intracellular
      signaling and the control of biochemical pathways in all living cells. Recent
      advances in high-performance MS/MS-based technology make the large-scale
      identification and quantification of phosphorylation sites possible. Here, we
      review the full data generation pipeline, starting from sample preparation
      methods and LC-MS detection procedures, through to data processing and analysis
      software tools that facilitate the systematic comparative profiling of thousands
      of phosphoproteins in different biological specimens in a single experiment. We
      emphasize current challenges and promising avenues for the mechanistic
      interpretation and visualization of global phosphorylation networks and their
      relevance to human health and disease.

PMID- 25384594
TI  - Recent advances in hydrophilic interaction chromatography for quantitative
      analysis of endogenous and pharmaceutical compounds in plasma samples.
AB  - There is an increasing need for new analytical methods that can handle a large
      number of analytes in complex matrices. Hydrophilic interaction chromatography
      (HILIC) has recently been demonstrated as an important supplement to reversed
      phase liquid chromatography for polar analytes, particularly endogenous
      compounds. With the increasing popularity of HILIC, progressively more polar
      phases with diverse functional groups have been developed. In addition, the
      coupling of HILIC to mass spectrometry offers the advantages of improved
      sensitivity by employing an organic-rich mobile phase. This article reviews
      recent applications of HILIC for the analysis of endogenous and pharmaceutical
      compounds in plasma samples. Furthermore, based on recent studies, we provide a
      discussion of column selection, sample pretreatment for HILIC analysis, and
      detection sensitivity.

PMID- 25384595
TI  - Current advances and strategies towards fully automated sample preparation for
      regulated LC-MS/MS bioanalysis.
AB  - Robotic liquid handlers (RLHs) have been widely used in automated sample
      preparation for liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      bioanalysis. Automated sample preparation for regulated bioanalysis offers
      significantly higher assay efficiency, better data quality and potential
      bioanalytical cost-savings. For RLHs that are used for regulated bioanalysis,
      there are additional requirements, including 21 CFR Part 11 compliance, software
      validation, system qualification, calibration verification and proper
      maintenance. This article reviews recent advances in automated sample preparation
      for regulated bioanalysis in the last 5 years. Specifically, it covers the
      following aspects: regulated bioanalysis requirements, recent advances in
      automation hardware and software development, sample extraction workflow
      simplification, strategies towards fully automated sample extraction, and best
      practices in automated sample preparation for regulated bioanalysis.

PMID- 25384596
TI  - Multidimensional gas chromatography methods for bioanalytical research.
AB  - Multidimensional gas chromatography (MDGC) methods are high-resolution volatile
      chemical separation techniques, and comprise classical heart-cutting MDGC and its
      more recent incarnation, comprehensive 2D GC. Although available for a long
      period, MDGC approaches are still not widely practiced in the field of
      bioanalysis, possibly reflecting the general preference for regular GC versus
      MDGC approaches. With the recent introduction of '-omic' techniques that
      emphasize global nontargeted profiling of metabolites within living systems, it
      is evident that MDGC is gaining momentum as a separation tool, since it offers
      very high resolution. By untangling metabolites within highly complex biological
      matrices, and expanding the metabolic coverage, MDGC plays a frontline role in '
      omics' based studies. This review highlights state-of-the-art MDGC approaches,
      and summarizes the recent developments in bioanalytics.

PMID- 25384597
TI  - Procedures and practices for the validation of bioanalytical methods using dried
      blood spots: a review.
AB  - Dried blood spot (DBS) sampling, the collection of whole blood samples on paper,
      is an emerging technique used for bioanalytical methods. Several analytical
      challenges, such as possible effects of spotting volume, hematocrit and spot
      inhomogeneity are identified for these methods, however, no regulatory-based
      guidelines for the specific validation of DBS-based assays are available
      hitherto. To date, 68 validation reports concerning methods for the quantitative
      determination of drugs in human DBS could be traced in the literature, with large
      differences in the extensiveness of the reported validations. This review aims to
      present an overview of these published validations. Additionally, the different
      challenges of DBS-based assays are discussed and recommendations on how to
      perform validation tests addressing these challenges are provided.

PMID- 25384600
TI  - Bias-free, solar-charged electric double-layer capacitors.
AB  - The conversion of solar energy with simultaneous electric energy storage provides
      a promising means for optimizing energy utilization efficiency and reducing
      device volume. In this paper, a 3-dimensional mesoporous carbon coated branched
      TiO2 nanowire composite is rationally designed for direct conversion and storage
      of solar energy as electric double-layer capacitive energy. The 1-dimensional,
      crystalline TiO2 trunks serve as long light absorption and continuous charge
      transport pathways, and the high-density TiO2 branches can efficiently increase
      the contact area with the surface coated mesoporous carbon layers. In addition,
      the ordered and uniformed mesopores provide large pore sizes for electrolyte
      penetration, and a high surface area for charge absorption and storage. Under a 1
      sun illumination and no external electric bias, this branched TiO2/mesoporous
      carbon composite exhibits specific capacitances of over 30 and 23.4 F g(-1), at
      current densities of 0.1 and 0.5 A g(-1), respectively. An excellent stability of
      >50 photocharging-electrical discharging cycles has also been demonstrated,
      suggesting the potential of further developing this hybrid material structure for
      simultaneous solar conversion and electric energy storage. 

PMID- 25384599
TI  - Landscape-seascape dynamics in the isthmus between Sorkapp Land and the rest of
      Spitsbergen: Will a new big Arctic island form?
AB  - Transformation of the glaciated isthmus between Sorkapp Land and the rest of
      Spitsbergen since 1900 is described. The landscape-seascape dynamics depends on
      the glacial recession determined by climate warming after the Little Ice Age
      (i.e., since the beginning of the twentieth century, and especially since the
      1980s). The isthmus has been narrowed from 28 km in 1899-1900 to 6.2 km in 2013,
      and lowered by 60-200 m from 1936 to 2005. Two isthmus' glaciers will have
      melted, given the current thermic conditions, by 2030-2035. It cannot be ruled
      out that Sorkapp Land will become an island after that period, because the
      altitude of the glaciers' bedrock is close to the sea level. The disappearance of
      this huge ice mass, even without origin of a sound and island, will lead to a
      great transformation of the landscape and the ecosystem.

PMID- 25384601
TI  - PdI2-catalyzed regioselective cyclocarbonylation of 2-allyl phenols to
      dihydrocoumarins.
AB  - A simple, efficient, and regioselective synthesis of 3-methyl-3,4
      dihydrocoumarins is reported. The reaction of 2-allyl phenols with synthesis gas
      was catalyzed by PdI2, and 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6
      phosphaadamantane (L1) and 1,3,5,7-tetramethyl-6-tetradecyl-2,4,8-trioxa-6
      phosphaadamantane (L2) were effective as ligands, affording good product
      selectivity in all cases. 

PMID- 25384602
TI  - Oxidative phosphorylation revisited.
AB  - The fundamentals of oxidative phosphorylation and photophosphorylation are
      revisited. New experimental data on the involvement of succinate and malate
      anions respectively in oxidative phosphorylation and photophosphorylation are
      presented. These new data offer a novel molecular mechanistic explanation for the
      energy coupling and ATP synthesis carried out in mitochondria and chloroplast
      thylakoids. The mechanism does not suffer from the flaws in Mitchell's
      chemiosmotic theory that have been pointed out in many studies since its first
      appearance 50 years ago, when it was hailed as a ground-breaking mechanistic
      explanation of what is perhaps the most important process in cellular energetics.
      The new findings fit very well with the predictions of Nath's torsional mechanism
      of energy transduction and ATP synthesis. It is argued that this mechanism, based
      on at least 15 years of experimental and theoretical work by Sunil Nath,
      constitutes a fundamentally different theory of the energy conversion process
      that eliminates all the inconsistencies in Mitchell's chemiosmotic theory pointed
      out by other authors. It is concluded that the energy-transducing complexes in
      oxidative phosphorylation and photosynthesis are proton-dicarboxylic acid anion
      cotransporters and not simply electrogenic proton translocators. These results
      necessitate revision of previous theories of biological energy transduction,
      coupling, and ATP synthesis. The novel molecular mechanism is extended to cover
      ATP synthesis in prokaryotes, in particular to alkaliphilic and haloalkaliphilic
      bacteria, essentially making it a complete theory addressing mechanistic,
      kinetic, and thermodynamic details. Finally, based on the new interpretation of
      oxidative phosphorylation, quantitative values for the P/O ratio, the amount of
      ATP generated per redox package of the reduced substrates, are calculated and
      compared with experimental values for fermentation on different substrates. It is
      our hope that the presentation of oxidative phosphorylation and
      photophosphorylation from a wholly new perspective will rekindle scientific
      discussion of a key process in bioenergetics and catalyze new avenues of research
      in a truly interdisciplinary field.

PMID- 25384603
TI  - Double-blinded, randomized controlled trial of N-acetylcysteine for prevention of
      acute kidney injury in high risk patients undergoing off-pump coronary artery
      bypass.
AB  - AIM: The aim of this study was to investigate the influence of perioperative N
      acetylcysteine (NAC) administration, a known antioxidant, on the incidence of
      acute kidney injury (AKI) after off-pump coronary bypass surgery (OPCAB) in
      patients with known risk factors of AKI. METHODS: One hundred and seventeen
      patients with >=1 of the following risk factors of AKI were randomized into
      either the control (n = 57) or the NAC (n = 60) group; (i) preoperative serum
      creatinine >1.4 mg/dL; (ii) left ventricular ejection fraction <35% or congestive
      heart failure (iii) age >70 years (iv) diabetes or (v) re-operation. Patients in
      the NAC group received 150 mg/kg of NAC IV bolus at anaesthetic induction
      followed by a continuous infusion at 150 mg/kg per day for 24 h. AKI was
      diagnosed based on Acute Kidney Injury Network criteria during 48 h
      postoperatively. RESULTS: The incidence of AKI was 32% (19/60) and 35% (20/57) in
      the control and the NAC group, respectively (P = 0.695). The serum concentrations
      of creatinine and cystatin C were similar between the groups throughout the study
      period. Fluid balance including the amount of blood loss and transfusion
      requirement were similar between the groups except the amount of postoperative
      urine output, which was higher in the control group compared with the NAC group
      (5528 +/- 1247 mL vs. 4982 +/- 1185 mL, control vs. NAC, P = 0.017). CONCLUSION:
      Perioperative administration of NAC did not prevent the development of
      postoperative AKI after OPCAB in highly susceptible patients to AKI.

PMID- 25384604
TI  - Mycobacterium fortuitum skin infections after subcutaneous injections with
      Vietnamese traditional medicine: a case report.
AB  - BACKGROUND: Iatrogenic skin and soft tissue infections by rapidly growing
      mycobacteria are described with increasing frequency, especially among
      immunocompromised patients. CASE PRESENTATION: Here, we present an
      immunocompetent patient with extensive Mycobacterium fortuitum skin and soft
      tissue infections after subcutaneous injections to relieve joint pains by a
      Vietnamese traditional medicine practitioner. Moreover, we present dilemmas faced
      in less resourceful settings, influencing patient management. CONCLUSION: This
      case illustrates the pathogenic potential of rapid growing mycobacteria in
      medical or non-medical skin penetrating procedures, their world-wide distribution
      and demonstrates the dilemmas faced in settings with fewer resources.

PMID- 25384605
TI  - Use of artificial neural networks to decision making in patients with lumbar
      spinal canal stenosis.
AB  - BACKGROUND: A lack of consensus exists regarding indications for surgery for
      lumbar spinal canal stenosis (LSCS). Hence, the aim of this study was to develop
      an artificial neural network (ANN) model that is designed to accurately select
      patients for surgery or non-surgical options and to compare such with the
      traditional clinical decision making approach in LSCS patients. METHODS: An ANN
      model and a logistic regression (LR) model were used as predicting models. The
      data for a total of 346 of 379 patients (143 male, 203 female, mean age 59.5+/
      11.5 years) were available for the analysis. The measured metrics included Visual
      Analog Scale (VAS) of leg pain/numbness, the Japanese Orthopedic Association
      (JOA) Score, the Neurogenic Claudication Outcome Score (NCOS), the Oswestry
      Disability Index (ODI), the Swiss Spinal Stenosis Score (SSS), the Stenosis
      Bothersomeness Index (SBI), the dural sac cross-sectional surface area (DSCA),
      the Stenosis Ratio (SR), the Self-Paced Walking Test (SPWT), morphology grade
      presented by Schizas et al. and grading system introduced by Lee et al.
      Successful outcome was recorded based on the criteria presented by Stucki et al.
      Twelve measures and age, gender, and duration of symptoms, were recorded as the
      input variables for the ANN and LR, and the ANN was fed with patients. A
      sensitivity analysis was applied to the developed ANN model to identify the
      important variables. Receiver operating characteristic (ROC) analysis, Hosmer
      Lemeshow (H-L) statistics and accuracy rate were calculated for evaluating the
      two models. The study was not supported by a grant and the authors declare that
      they have no conflict of interest. RESULTS: The patient information was divided
      into training (N.=174), testing (N.=86), and validation (N.=86) data sets.
      Successful outcome were achieved in 93.4% of the patients selected for surgery
      and 89.4% for non-surgery at 1-year follow-up. The SR, morphology grade and
      grading system were important variables identified by the ANN. The ANN model
      displayed better accuracy rate (97.8 %), a better H-L statistic (41.1 %) which
      represented a good-fit calibration, and a better AUC (89.0%), compared to the LR
      model. CONCLUSIONS: The findings showed that an ANN model can predict the optimal
      treatment choice for LSCS patients in clinical setting and is superior to LR
      model. Our results will need to be confirmed with external validation studies.

PMID- 25384606
TI  - Neuroendoscopic choroid plexus coagulation in the current pediatric neurosurgery.

PMID- 25384608
TI  - Self-Confidence and Paranoia: An Experimental Study Using an Immersive Virtual
      Reality Social Situation.
AB  - BACKGROUND: Paranoia may build directly upon negative thoughts about the self.
      There have been few direct experimental tests of this hypothesis. AIMS: The aim
      of the study was to test the immediate effects of manipulating self-esteem in
      individuals vulnerable to paranoia. METHOD: A two condition cross-over
      experimental test was conducted. The participants were 26 males reporting
      paranoid ideation in the past month. Each participant experienced a neutral
      immersive virtual reality (VR) social environment twice. Before VR participants
      received a low self-confidence manipulation or a high self-confidence
      manipulation. The order of manipulation type was randomized. Paranoia about the
      VR avatars was assessed. RESULTS: The low self-confidence manipulation, relative
      to the high self-confidence manipulation, led to significantly more negative
      social comparison in virtual reality and higher levels of paranoia. CONCLUSIONS:
      Level of self-confidence affects the occurrence of paranoia in vulnerable
      individuals. The clinical implication is that interventions designed to improve
      self-confidence may reduce persecutory ideation.

PMID- 25384607
TI  - Reference values for healthy human myocardium using a T1 mapping methodology:
      results from the International T1 Multicenter cardiovascular magnetic resonance
      study.
AB  - BACKGROUND: T1 mapping is a robust and highly reproducible application to
      quantify myocardial relaxation of longitudinal magnetisation. Available T1
      mapping methods are presently site and vendor specific, with variable accuracy
      and precision of T1 values between the systems and sequences. We assessed the
      transferability of a T1 mapping method and determined the reference values of
      healthy human myocardium in a multicenter setting. METHODS: Healthy subjects
      (n=102; mean age 41 years (range 17-83), male, n=53 (52%)), with no previous
      medical history, and normotensive low risk subjects (n=113) referred for clinical
      cardiovascular magnetic resonance (CMR) were examined. Further inclusion criteria
      for all were absence of regular medication and subsequently normal findings of
      routine CMR. All subjects underwent T1 mapping using a uniform imaging set-up
      (modified Look- Locker inversion recovery, MOLLI, using scheme 3(3)3(3)5)) on 1.5
      Tesla (T) and 3 T Philips scanners. Native T1-maps were acquired in a single
      midventricular short axis slice and repeated 20 minutes following gadobutrol.
      Reference values were obtained for native T1 and gadolinium-based partition
      coefficients, lambda and extracellular volume fraction (ECV) in a core lab using
      standardized postprocessing. RESULTS: In healthy controls, mean native T1 values
      were 950+/-21 msec at 1.5 T and 1052+/-23 at 3 T. lambda and ECV values were
      0.44+/-0.06 and 0.25+/-0.04 at 1.5 T, and 0.44+/-0.07 and 0.26+/-0.04 at 3 T,
      respectively. There were no significant differences between healthy controls and
      low risk subjects in routine CMR parameters and T1 values. The entire cohort
      showed no correlation between age, gender and native T1. Cross-center comparisons
      of mean values showed no significant difference for any of the T1 indices at any
      field strength. There were considerable regional differences in segmental T1
      values. lambda and ECV were found to be dose dependent. There was excellent inter
      and intraobserver reproducibility for measurement of native septal T1.
      CONCLUSION: We show transferability for a unifying T1 mapping methodology in a
      multicenter setting. We provide reference ranges for T1 values in healthy human
      myocardium, which can be applied across participating sites.

PMID- 25384609
TI  - Current treatment options with immunoglobulin G for the individualization of care
      in patients with primary immunodeficiency disease.
AB  - Primary antibody deficiencies require lifelong replacement therapy with
      immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both
      subcutaneous and intravenous routes of administering IgG can be effective and
      well tolerated. Treatment regimens can be individualized to provide optimal
      medical and quality-of-life outcomes in infants, children, adults and elderly
      people. Frequency, dose, route of administration, home or infusion-centre
      administration, and the use of self- or health-professional-administered infusion
      can be tailored to suit individual patient needs and circumstances. Patient
      education is needed to understand the disease and the importance of continuous
      therapy. Both the subcutaneous and intravenous routes have advantages and
      disadvantages, which should be considered in selecting each patient's treatment
      regimen. The subcutaneous route is attractive to many patients because of a
      reduced incidence of systemic adverse events, flexibility in scheduling and its
      comparative ease of administration, at home or in a clinic. Self-infusion
      regimens, however, require independence and self-reliance, good compliance on the
      part of the patient/parent and the confidence of the physician and the nurse.
      Intravenous administration in a clinic setting may be more appropriate in
      patients with reduced manual dexterity, reluctance to self-administer or a lack
      of self-reliance, and intravenous administration at home for those with good
      venous access who prefer less frequent treatments. Both therapy approaches have
      been demonstrated to provide protection from infections and improve health
      related quality of life. Data supporting current options in IgG replacement are
      presented, and considerations in choosing between the two routes of therapy are
      discussed. 

PMID- 25384610
TI  - Biocontrol of Fusarium wilt disease in tomato by Paenibacillus ehimensis KWN38.
AB  - This study was conducted to investigate biocontrol potential of Paenibacillus
      ehimensis KWN38 against Fusarium oxysporum f.sp. lycopersici causing Fusarium
      wilt disease in tomato. Our result showed that P. ehimensis KWN38 produced
      extracellular organic compounds and crude enzyme to inhibit F. oxysporum f.sp.
      lycopersici conidial germination in in vitro assays. Tomato seedlings were
      treated with water (W), grass medium (G), G with P. ehimensis KWN38 inoculation
      (GP) and G along with synthetic fungicide (GSf). Disease symptoms were was first
      observed in G and W at 12 days after infection (DAI) while symptoms were
      noticeable in the GP and GSf treatments at 20 and 24 DAI, respectively. Tomato
      plants treated with P. ehimensis KWN38 or fungicide significantly reduced
      Fusarium wilt disease incidence and severity as compared to control tomato plants
      treated with water and grass medium. The similar results were also found in the
      root mortality of tomato plants. At 25 DAI, most plants in control treatments (W
      and G) wilted and the brown vascular systems of infected plants was clearly
      differentiable from normal green vascular system of healthy plants from GP and
      GSf. Plants in the GP showed higher fresh and dry weights of both root and shoots
      than those in W and G treatments. Leaf peroxidase and polyphenol oxidase
      activities of tomato plants in G and W were higher than those in GP and GSf. Root
      enzyme activities showed a similar pattern but the values were higher than leaf
      enzyme. The results clearly demonstrated that P. ehimensis KWN38 may be
      considered as biocontrol agent of Fusarium wilt disease in tomato. 

PMID- 25384611
TI  - Antifungal activity of volatile compounds-producing Pseudomonas P2 strain against
      Rhizoctonia solani.
AB  - Several volatile organic compounds (VOCs) producing endophyte bacteria were
      isolated from the leaves of olive trees and tested for their antifungal activity
      against several pathogenic fungi. An antagonistic strain called P2 showed 97 % of
      homology with Pseudomonas sp. strains on the basis of its 16S rDNA sequence and
      biochemical properties. P2 strain drastically inhibited the growth of Rhizoctonia
      solani mycelia (86 %) at 5 day-post-confrontation (dpc) and strongly reduced
      fungi infection on potato slices at 10(7) bacteria ml(-1) for 3 and 7 dpc. P2
      strain was also positive for protease activity as well as siderophore production.
      Light microscopy analysis showed that treatment of R. solani mycelia with P2
      strain induced thickening of the cell-wall, vesiculation of protoplasm and
      blockage of fungal hyphae branching. VOCs analysis using GC-MS allowed the
      detection of two major products with m/z of 93.9910 and 125.9630 corresponding to
      dimethyl disulfide and dimethyl trisulfide respectively. VOCs-producing P2 strain
      could be a promising agent in the protection of tuber crops against fungal
      diseases. 

PMID- 25384612
TI  - Transition of chytrid fungus infection from mouthparts to hind limbs during
      amphibian metamorphosis.
AB  - The chytrid fungus, Batrachochytrium dendrobatidis (Bd), is implicated in
      worldwide amphibian declines. Bd has been shown to qualitatively transition from
      the mouthparts of tadpoles to the hindlimbs during metamorphosis, but we lack
      evidence of consistency in the timing of this transition across amphibian
      species. We also do not have predictive functions for the abundance of Bd in
      mouthparts and limbs as tadpoles develop or for the relationship between keratin
      and Bd abundance. Hence, researchers presently have little guidance on where to
      sample developing amphibians to maximize Bd detection, which could affect the
      accuracy of prevalence and abundance estimates for this deadly pathogen. Here, we
      show consistency in the timing of the transition of Bd from mouthparts to hind
      limbs across two frog species (Osteopilus septentrionalis and Mixophyes
      fasciolatus). Keratin and Bd simultaneously declined from the mouthparts starting
      at approximately Gosner stage 40. However, keratin on the hindlimbs began to
      appear at approximately stage 38 but, on average, Bd was not detectable on the
      hindlimbs until approximately stage 40, suggesting a lag between keratin and Bd
      arrival. Predictive functions for the relationships between developmental stage
      and keratin and developmental stage and Bd for mouthparts and hind limbs are
      provided so that researchers can optimize sampling designs and minimize erroneous
      conclusions associated with missing Bd infections or misestimating Bd abundance. 

PMID- 25384613
TI  - The prevalence of arrhythmias, predictors for arrhythmias, and safety of exercise
      stress testing in children.
AB  - Exercise testing is commonly performed in children for evaluation of cardiac
      disease. Few data exist, however, on the prevalence, types of arrhythmias,
      predictors for arrhythmias, and safety of exercise testing in children. A
      retrospective review of all patients <=21 years undergoing exercise testing at
      our center from 2008 to 2012 was performed. Patients with clinically relevant
      arrhythmias were compared to those not experiencing a significant arrhythmia.
      1,037 tests were performed in 916 patients. The mean age was 14 +/- 4 years, 537
      (55 %) were male, 281 (27 %) had congenital heart disease, 178 (17 %) had a
      history of a prior arrhythmia, and 17 (2 %) had a pacemaker or ICD. 291 (28 %)
      patients had a rhythm disturbance during the procedure. Clinically important
      arrhythmias were noted in 34 (3 %) patients and included: 19 (1.8 %) increasing
      ectopy with exercise, 5 (0.5 %) VT, 5 (0.5 %) second degree AV block, 3 (0.3 %)
      SVT, and 2 (0.2 %) AFIB. On multivariate logistic regression, variables
      associated with the development of clinically relevant arrhythmias included
      severe left ventricular (LV) dysfunction on echo (OR 1.99, CI 1.20-3.30) and
      prior history of a documented arrhythmia (OR 2.94, CI 1.25-6.88). There were no
      adverse events related to testing with no patient requiring cardioversion,
      defibrillation, or acute anti-arrhythmic therapy. A total of 28 % of children
      developed a rhythm disturbance during exercise testing and 3 % were clinically
      important. Severe LV dysfunction and a history of documented arrhythmia were
      associated with the development of a clinically important arrhythmia. 

PMID- 25384615
TI  - Main group catalysed reduction of unsaturated bonds.
AB  - This Perspective highlights the recent developments in the reduction of
      unsaturated substrates catalysed by main group element compounds. Various
      activation modes are discussed and comparison with relevant examples from
      transition metal systems is made when possible. Main group element catalysis
      offers significant advantages through its lower cost and more benign
      environmental impact and has now reached the point where it can successfully
      compete with the more common catalysis based on precious transition metals. 

PMID- 25384614
TI  - Chylous ascites after laparoscopic donor nephrectomy.
AB  - INTRODUCTION: The aim of this study was to determine the incidence, presentation,
      management, and outcomes of chylous ascites following laparoscopic donor
      nephrectomy. METHODS: An Internet-based, multi-institutional survey was performed
      using http://www.surveymonkey.com. An email invitation to the voluntary survey
      was sent to 30 transplant centers and posted on CenterSpan, an email forum for
      transplant surgeons. The number of living donor transplantations and the number
      of cases of chylous ascites with clinical information, treatment and outcomes
      were sought from the questionnaire. RESULTS: A total of 12 centers responded and
      reported 7683 cases of live donor nephrectomy. The reported incidence of
      postoperative chylous ascites was 0.013% (n = 12). Six centers reported 10 cases
      of chylous ascites following laparoscopic donor nephrectomy and 2 cases after
      open donor nephrectomy. Among the eight patients who developed chylous ascites
      following laparoscopic donor nephrectomy, presentation was typically 2 weeks
      after the date of initial surgery. Conservative therapy was successful in 50% of
      cases. Refractory ascites managed secondarily with surgical intervention had a
      success rate of 100%. CONCLUSION: Chylous ascites is a rare complication
      following laparoscopic donor nephrectomy. Initial treatment should be
      conservative, with surgical therapy reserved for refractory cases.

PMID- 25384616
TI  - The effect of propofol on the expression of rabbit ischemia reperfusion injury
      related proteins.
AB  - To investigate the effect of propofol on the expression of rabbit ischemia
      reperfusion injury-related proteins and the mechanism involved. Thirty healthy
      adult New Zealand rabbit were selected. After establishment of liver I/R model,
      the rabbits were divided into group A (sham operation group), group B (control
      group using saline), and group C (propofol group) with ten rabbits in each group.
      The total protein concentration, differentially expressed protein spots and the
      difference of apoptotic proteins expression levels among the three groups were
      compared. The total protein concentrations in group A, B, and C were 0.778,
      0.835, and 0.765 MUg/MUl, respectively, and the protein concentration in group B
      was significantly higher than group A and C (p < 0.05), with no significant
      difference between group A and C (p > 0.05); results analyzed by PDQuest software
      showed that the average number of protein spots and matching ratio had no
      significant difference among the three groups (p > 0.05); MALDI-TOF-MS mass
      spectrometry identified 16 differentially expressed protein spots; the numbers of
      Caspase-3 positive cells in group B and C were significantly higher than those in
      group A, and the numbers of Bcl-2 and Bax positive cells in group B and C were
      significantly lower than those in group A (p < 0.05); the number of Capase-3
      positive cells in group C was significantly higher than those in group B, and the
      number of Bcl-2 positive cells in group C was significantly lower than those in
      group B (p < 0.05). The numbers of Bax positive cells had no significant
      difference between group B and C (p > 0.05); densities of Caspase-3, Bcl-2 and
      Bax in group B and C were significantly higher than those in group A (p < 0.05);
      Western blotting results from the comparison of the number of positive cells
      between group B and C was in accordance to the result obtained from
      immunohistochemistry. After I/R injury in rabbit, there was deregulation of
      various proteins such as Caspase-3, Bcl-2 and Bax, which was an important factor
      contributing to liver injury even systematic disease. Propofol could regulate the
      expression of I/R injury-related proteins and inhibit the attack of free radical
      to liver, having a remarkable advantage in preventing I/R injury and controlling
      the development of I/R injury. This study provides an effective theoretical basis
      for the prevention and treatment of I/R injury.

PMID- 25384617
TI  - Dual role of P2 receptors during osteoblast differentiation.
AB  - P2 receptors activated by ATP are expressed in the skeletal system. However, the
      role of P2 receptors in osteoblast differentiation remains unclear. METHODS:
      Participation of P2 receptors in differentiation was investigated in the
      preosteoblast MC3T3-M1 cell line. Preosteoblasts were stimulated for 7 or 14 days
      in the presence of osteogenic medium containing ATP and its analogs, and then
      alkaline phosphatase (ALP) activity, gene expression analyses, and protein
      expression were assessed. RESULTS: We observed that ATP and its analogs promoted
      increased ALP activity after 7 days of treatment. In contrast, these agonists
      promoted reductions in ALP activity after 14 days. Some antagonists, such as
      PPADS (P2 antagonist), MRS2179 (P2Y1 antagonist), MRS2578 (P2Y6 antagonist), and
      AZ11645373 (P2X7 antagonist) reduced the increases in ALP activity after 7 days.
      However, only AZ11645373 inhibited the reduction in ALP activity after 14 days.
      The expression of the P2Y2, P2Y6, P2X4, and P2X7 receptors was observed.
      Furthermore, treatment with ATP modulated the expression of P2 receptors,
      increasing P2X4 expression and reducing P2Y6 and P2X7 expression. Similar results
      were observed after 14 days. In addition, ATP treatment for 7 days increased the
      expression of transcription factors associated with osteoblast differentiation,
      such as Runx2, SP7, and Dix5, whereas SP7 and Dix5 expression was reduced at 14
      days. These results suggest that P2 receptor activation modulates the
      differentiation of osteoblasts and is dependent upon the stage of
      differentiation. These results also suggest that several P2 receptors are
      involved in this process.

PMID- 25384618
TI  - Hydrotubation combined with chinese herbal medicine for salpingitic infecundity:
      a systematic review and meta-analysis.
AB  - Salpingitis is a major cause of infertility. Clinical studies about hydrotubation
      combined with Chinese herbal medicine (CHM) for salpingitic infecundity are
      increasing, while systematic reviews about its efficacy remain inexistent.
      Assessing the effectiveness of hydrotubation combined with CHM for salpingitic
      infecundity. Randomized controlled trials were retrieved from different seven
      databases. One thousand three hundred and thirty-seven papers were collected and
      only 16 randomized clinical trials met the requirements and were included. The
      meta-analysis indicated that hydrotubation combined with CHM was associated with
      a higher pregnancy rate and a lower ectopic pregnancy rate compared to
      hydrotubation alone. The success rate of recanalization was significantly
      increased, as well as signs and symptoms were better alleviated in patients
      treated with hydrotubation combined with CHM. The clinical data available
      indicate that compared with hydrotubation alone, hydrotubation combined with CHM
      for salpingitic infecundity has better therapeutic effects. 

PMID- 25384619
TI  - Synergistic Anti-Cancer Effects of Icariin and Temozolomide in Glioblastoma.
AB  - Glioblastoma is an aggressive malignancy, which is associated with poor
      prognosis. Temozolomide (TMZ) has been showed to be an effective chemotherapeutic
      agent for glioblastoma treatment; however, the response rate is not satisfactory.
      Icariin is a natural compound with anti-cancer activity against a variety of
      cancers. This study is designed to determine whether icariin could potentiate the
      antitumor activity of TMZ in glioblastoma. Cell proliferation and apoptosis were
      measured using MTT assay and flow cytometry, respectively. Expression of
      apoptosis and proliferation-related molecules was detected by Western blotting
      while NF-kappaB activity was detected by ELISA. Icariin dose-dependently
      inhibited proliferation and induced apoptosis in tested glioblastoma cell lines.
      Icariin enhanced the anti-tumor activity of TMZ in vitro. The anti-tumor activity
      of icariin and the enhanced anti-tumor activity of TMZ by icariin correlated with
      suppression of NF-kappaB activity. Our results showed that icariin exhibited anti
      tumor activity and potentiated the anti-tumor activity of TMZ in glioblastoma, at
      least in part, by inhibiting NF-kappaB activity. Although more studies including
      clinical trials are needed, this study provides insight for using icariin as a
      chemosensitizing agent in clinic settings. 

PMID- 25384620
TI  - Physicochemical characterization of native glycyl-l-histidyl-l-lysine tripeptide
      for wound healing and anti-aging: a preformulation study for dermal delivery.
AB  - This study investigates the physicochemical properties of glycyl-histidyl-lysine
      copper (GHK-Cu) to support the development of a formulation for effective topical
      delivery. The solubility and distribution coefficients (log D) were investigated
      using conventional methods and GHK concentrations were quantified with a
      validated stability-indicating reversed phase high performance liquid
      chromatography (RP-HPLC) method. In addition, the stability of GHK-Cu under
      stressed conditions and the compatibility with some potential formulation
      components were assessed. The peptide was susceptible to hydrolytic cleavage
      under basic and oxidative stressors and to a lesser extent acidic stress with
      first-order degradation profiles. Surprisingly, the peptide was stable in water
      and in pH (4.5-7.4) buffers for at least two weeks at 60   degrees C. The HPLC in
      conjunction with mass spectrometry identified three key degradation products, one
      of which was the constituent amino acid histidine. The distribution coefficients
      in octanol-phosphate buffered saline indicated the highly hydrophilic nature of
      GHK-Cu with log D values between -2.38 and -2.49 at pH range of 4.5-7.4.
      Furthermore, GHK-Cu was compatible with Span 60 based niosomes but less stable in
      the presence of the negatively charged lipid dicetyl phosphate. In summary, the
      preformulation studies provided information useful to deliver the GHK-Cu complex
      by carrier. 

PMID- 25384621
TI  - Chiroptical detection of nonchromophoric, achiral guests by enantiopure alleno
      acetylenic helicages.
AB  - Enantiopure alleno-acetylenic ligands assemble diastereoselectively upon the
      addition of a zinc(II) salt to form triple-stranded helicates, which provide a
      sufficiently large helical cage ("helicage") for the encapsulation of guests. The
      inclusion complexation of heteroalicycles is confirmed by ROESY and DOSY NMR
      spectroscopy and quantified in (1) H NMR binding titrations. The ECD spectra of
      the helicates, which showed strong Cotton effects and exciton coupling, were
      found to be extremely sensitive to the nature of the guest molecules.
      Consequently, a series of nonchromophoric, achiral guests of different sizes as
      well as regioisomers (1,3- and 1,4-dioxane) became distinguishable on the basis
      of their induced CD (ICD) spectra. Molecular dynamics (MD) simulations show the
      adaptability of the cavity size to individual guest molecules and support the
      selective ICD output. Particularly high affinity towards 1,4-dioxane allowed its
      selective detection at parts-per-million (ppm) levels in aqueous solutions. 

PMID- 25384622
TI  - Color change of the snapper (Pagrus auratus) and Gurnard (Chelidonichthys kumu)
      skin and eyes during storage: effect of light polarization and contact with ice.
AB  - Ten gurnard and 10 snapper were stored on ice. One side always contacted the ice;
      the other side was always exposed to air. At different intervals for up to 12 d,
      the fish were placed in a light box, and the images of both sides were taken
      using polarized and nonpolarized illumination. Image analysis resulted in average
      L*, a*, and b* values of skin, and average L* values of the eyes. The skin L*
      value of gurnard changed significantly over time while that of snapper was
      substantially constant. The a* and b* values of both fish decreased over time.
      The L* values of eyes were significantly lower for polarized images, and
      significantly lower for the side of fish exposed to air only. This may be a
      concern in quality evaluation methods such as QIM. The difference of colors
      between the polarized and nonpolarized images was calculated to quantify the
      reflection off the surface of fish. For accurate measurement of surface color and
      eye color, use of polarized light is recommended. 

PMID- 25384623
TI  - Distribution of small phytoflagellates along an Arctic fjord transect.
AB  - Phytoflagellates <10 MUm substantially contribute to the abundance, biomass and
      primary production in polar waters, but information on the distribution of
      specific groups is scarce. We applied catalysed reporter deposition-fluorescence
      in situ hybridization to investigate the distribution of total phytoflagellates
      and of eight specific groups along a 100 km transect west off Kongsfjorden
      (Spitsbergen) from 29 to 31 July 2010. Phytoflagellates contributed to >75% of
      the depth-integrated abundance and biomass of total eukaryotes <10 MUm at all
      stations. Their depth-integrated abundance and biomass decreased along the
      transect from 1.5 * 10(12)  cells m(-2) (6.6 * 10(12)  pgC m(-2) ) at the
      outermost station to 1.7 * 10(10)  cells m(-2) (4.7 * 10(10) pgC m(-2) ) at the
      innermost station. Chlorophytes contributed to the total abundance of
      phytoflagellates with a range from 13% to 87% (0.7-30.5 * 10(3)  cells ml(-1) ),
      and predominated in open waters. The contribution of haptophytes was < 1-38% (10
      4500 cells ml(-1) ). The other groups represented <10%. The temperature and
      salinity positively correlated with the total abundance of phytoflagellates,
      chlorophytes, haptophytes, bolidophytes and pelagophytes. Cryptophytes,
      pedinellids and pavlovophytes were negatively associated with the nutrient
      concentrations. The community composition of phytoflagellates changed along the
      transect, which could have implications on food web dynamics and biogeochemical
      cycles between the open ocean environment and Kongsfjorden investigated here.

PMID- 25384624
TI  - Antibody and cell-mediated immune response to whole virion and split virion
      influenza vaccine in patients with inflammatory bowel disease on maintenance
      immunosuppressive and biological therapy.
AB  - OBJECTIVE: Influenza vaccination is recommended for inflammatory bowel disease
      (IBD) patients on immunosuppressive therapy. The objective was to evaluate the
      antibody and cell-mediated immune response to the split and whole virion
      influenza vaccine in patients with IBD treated with anti-TNF-alpha and
      immunosuppressive therapy. PATIENTS AND METHODS: One hundred and fifty-six
      immunocompromised IBD patients were vaccinated. Fifty-three patients (control
      group) refused vaccination. Split virion vaccine and whole virion vaccine were
      used. Serum samples were obtained for pre- and postimmunization antibody titers
      to influenza vaccine (A/California/7/2009 [H1N1], A/Victoria/361/2011 [H3N2],
      B/Wisconsin/1/2010-like B/Hubei-Wujiagang/158/2009). Cell-mediated response was
      evaluated using an interferon (INF)-gamma, interleukine (IL)-2 and tumor necrosis
      factor (TNF)-alpha ELISA. RESULTS: Postimmunization titers of both influenza
      subtypes increased significantly after the administration of split virion
      vaccines compared to the controls and to those who received whole virion vaccine.
      The antibody titers of Influenza B also increased significantly in patients
      immunized with split vaccine and treated with anti-TNF-alpha therapy. After
      influenza vaccination, the level of serum IL-2 significantly decreased. No
      serious side effects developed occurred after influenza vaccination, and the
      influenza-like symptoms did not differ significantly between vaccinated versus
      control patients. The relapse of the disease was observed in only 10% of the
      patients and was more common in vaccinated than in control subjects. CONCLUSION:
      Split virion vaccines seem to be more effective than whole virion vaccines.
      Measuring the antibody responses is worthwhile in patients treated with
      immunosuppressants to determine the efficacy of influenza vaccination.

PMID- 25384625
TI  - Lipase-supported metal-organic framework bioreactor catalyzes warfarin synthesis.
AB  - A green and sustainable strategy synthesizes clinical medicine warfarin
      anticoagulant by using lipase-supported metal-organic framework (MOF) bioreactors
      (see scheme). These findings may be beneficial for future studies in the
      industrial production of chemical, pharmaceutical, and agrochemical precursors. 

PMID- 25384626
TI  - Control of fouling formation in membrane ultrafiltration by ultrasound
      irradiation.
AB  - The increasing application of membrane filtration in water and wastewater
      treatment necessitates techniques to improve performance, especially in fouling
      control. Ultrasound is one promising technology for this purpose as cavitational
      effects facilitate continuous cleaning of the membrane. This research studied the
      ultrafiltration of lake water in systems with constant permeate flux under medium
      frequency (45 kHz) ultrasound irradiation. Fouling was investigated by monitoring
      transmembrane pressure (TMP) using continuous or intermittent ultrasound
      irradiation and dead-end or crossflow operation. Best performance was observed
      with continuous ultrasound irradiation in crossflow mode. Intermittent
      irradiation reduced the rate of TMP build-up but nevertheless allowed
      irreversible fouling to develop. 

PMID- 25384627
TI  - Photopic negative response in branch retinal vein occlusion with macular edema.
AB  - In patients with branch retinal vein occlusion (BRVO) and macular edema, the
      relations among full-field electroretinogram (ffERG) parameters and parameters of
      retinal function or morphology remain uncertain. The objective of this study was
      to investigate the correlations between parameters of the ffERG, including the
      photopic negative response (PhNR), and retinal functional or morphological
      parameters in these patients. In 62 consecutive BRVO patients (mean age: 68.5 +/-
      10.6 years; 32 women and 30 men), the amplitude and implicit time of the a-wave
      cone, b-wave cone, 30 Hz flicker, and PhNR were calculated from the ffERG.
      Microperimetry was employed to measure the macular sensitivity within the central
      4 degrees , 10 degrees , and 20 degrees  fields, while macular thickness and
      volume within these fields were measured by optical coherence tomography. Best
      corrected visual acuity (BCVA) was determined on the logarithm of the minimum
      angle of resolution scale. The cone b-wave, 30 Hz flicker, and PhNR amplitudes
      showed a significant correlation with BCVA. In addition, the cone a-wave, cone b
      wave, 30 Hz flicker, and PhNR amplitudes all showed a significant correlation
      with macular sensitivity within the central 4 degrees , 10 degrees , and 20
      degrees  fields. Only the 30 Hz flicker amplitude showed a significant
      correlation with the macular thickness and volume within the 4 degrees , 10
      degrees , and 20 degrees  fields, while the other ERG parameters did not. These
      findings suggest that PhNR may be a useful ERG parameter for evaluating inner
      retinal function in BRVO patients.

PMID- 25384629
TI  - Psychological treatments for functional non-epileptic attacks: a systematic
      review.
AB  - OBJECTIVE: There is a lack of clarity about the most useful intervention for
      functional non-epileptic attacks (FNEA). Outcomes for this condition remain often
      poor, with considerable personal, social and economic impact. In order to guide
      clinical practice and future research in this area, we have performed a
      systematic review of the published literature on the psychological treatment of
      FNEA. METHODS: A comprehensive literature search was carried out using key words:
      non-epileptic seizures; psychogenic seizures; psychogenic non-epileptic seizures;
      pseudoseizures; funny turns; non-epileptic attack; hysterical seizures; and
      pseudoepileptic. Studies specifically looking at psychological treatment of FNEA
      were identified. Studies of patients also having comorbid organic seizure
      disorders were excluded. RESULTS: 17 studies that met the inclusion criteria were
      identified. A broad variety of psychological interventions for FNEA has been
      investigated. Only one randomised controlled trial has been completed to date.
      Existing evidence appears to suggest that various psychological treatments,
      including presenting the diagnosis, psychoeducation, behavioural therapies and
      mixed modality treatments, may be effective. CONCLUSION: While a range of
      psychological treatments may be beneficial for this patient group, we do not have
      clear evidence to suggest which treatment is most efficacious. Specific elements
      of presenting the diagnosis and psychoeducation may be required in addition to
      traditional cognitive behavioural therapeutic approaches. Large, methodologically
      robust studies are urgently required to establish the most effective form of
      treatment.

PMID- 25384628
TI  - Susceptibility of bacterial isolates to vancomycin and ceftazidime from patients
      with endophthalmitis: Is there a need to change the empirical therapy in
      suspected bacterial endophthalmitis?
AB  - To review the susceptibility of bacterial isolates to ceftazidime and vancomycin
      isolated from patients with endophthalmitis. Microbiology records of patients
      with endophthalmitis between June 2010 and May 2013 were reviewed. Vitreous and
      AC fluids obtained from patients with endophthalmitis were subjected to direct
      microscopy examination and culture. Antibiotic susceptibility of the isolates was
      performed by Kirby Bauer disk diffusion method. Resistant to ceftazidime in Gram
      negative bacteria (GNB) by disk diffusion method is confirmed by minimum
      inhibitory concentration using E test. Culture was positive for bacteria/Fungi in
      224/356 patients (62.9 %). Out of 224 patients, 191 (85.2 %) patients showed
      bacterial growth and 33 (14.0 %) showed fungal growth. Mixed bacterial infection
      was seen in five patients. Among the GNB, 23/123 (18 %) of the isolates were
      resistant to ceftazidime, and all the Gram positive bacteria 73/73 (100 %) were
      susceptible to vancomycin. Sixteen of 123 (13 %) GNB were resistant to amikacin.
      Although there is an increase in resistance to ceftazidime compared to amikacin
      in GNB, amikacin intravitreal injection is associated with macular toxicity and
      no single antibiotic has full coverage for all GNB. Combination of vancomycin and
      ceftazidime empiric therapy can be continued in patients with suspected
      endophthalmitis and treatment is modified based on clinical response and
      susceptibility results.

PMID- 25384630
TI  - Psychological factors, immune function and recovery from major surgery.
AB  - OBJECTIVE: This study used a prospective design and the technique of structural
      modelling to examine the complex interrelations between psychological factors,
      immune status and complications after major surgery. METHODS: Twenty-nine women
      scheduled for elective cholecystectomy were studied prospectively. Information
      regarding medical history, health practices, life stressors, and coping
      strategies was obtained two weeks prior to admission. At this initial meeting, as
      well as three days after surgery, and at one month follow-up immunological tests
      were performed and the level of psychological distress was assessed. The study
      additionally included measures of post-operative complications, and infections
      and negative effect during follow-up. RESULTS: Pre-operative immune status
      emerged as a key variable exerting strong effects on subsequent immune function
      and, thereby producing significant, indirect effects on every recovery variable.
      Pre-operative distress was directly linked to increased mood disturbance at
      follow-up. Moreover, distress significantly influenced immune function both
      before and after surgery, which mediated a significant impact on most recovery
      variables. Active coping behaviour directly increased the risk of a complicated
      recovery. CONCLUSIONS: The study demonstrated that distress-induced changes in
      immune functioning have clinical relevance. Overall, the present findings suggest
      that recovery from surgery is facilitated in patients with a well-functioning
      immune system, a low-level of pre-operative distress and a passive coping
      disposition.

PMID- 25384631
TI  - Decreased drug-cue-induced attentional bias in individuals with treated and
      untreated drug dependence.
AB  - OBJECTIVE: The present study investigated the attentional bias induced by drug
      related stimuli in active abusers; abstinent abusers on opioid substitution
      therapy; and abstinent drug-dependent patients in recovery on a community-based
      non-pharmacological therapy programme. Drug-dependent groups included both
      cocaine and heroin abusers. METHODS: Classical and emotional Stroop tasks were
      used to test all drug-dependent patients and controls with no history of
      addiction. Response times were recorded. An interference effect was obtained by
      comparing the congruent and incongruent conditions in the classical Stroop
      version. An attentional bias towards drug cues was derived by comparing latencies
      in the neutral and emotional conditions of the emotional Stroop. RESULTS: No
      between-group differences were found in the classical Stroop. In the emotional
      Stroop, active drug-dependent patients showed higher attentional bias (i.e.
      longer response times to drug-related words) than any of the other three groups.
      CONCLUSION: The attentional bias induced by drug cues in patients with addiction
      disorder might change depending on the patients' clinical status. All treated
      patients, whether on opioid substitution therapy or on community therapy, showed
      less attentional bias towards drug-related stimuli than active drug users,
      although the observed smaller bias was most likely induced by therapy acting
      through different mechanisms. Although drug-cues response is influenced by other
      multiple variables, e.g. motivation, craving, classical conditioning and
      substance availability, these data lend support to the hypothesis that treatment
      might contribute to decrease the attentional bias towards drug cues, which seems
      to play a critical role in achieving a positive outcome in the treatment of
      addiction.

PMID- 25384632
TI  - Lack of association between BDNF Val66Met gene polymorphism and late-onset
      depression in a Chinese Han population.
AB  - BACKGROUND: Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF)
      gene has been suggested to be associated with major depressive disorder (MDD).
      There were a few reports of the relationship between the variant and late-onset
      depression (LOD) in Chinese Han population. OBJECTIVE: To investigate the
      relationship among BDNF Val66Met gene variants, BDNF plasma level and LOD.
      METHODS: Chinese Han patients with LOD (n = 99) and control subjects (n = 110)
      were assessed for BDNF Val66Met gene polymorphism. BDNF plasma level was tested
      only in LOD. RESULTS: There were no significant differences in genotypes and
      allele frequencies between cases and controls (p = 0.744 and p = 0.845,
      respectively). Plasma BDNF level also did not show significant differences in
      three genotypes in LOD (p = 0.860). CONCLUSION: The Val66Met polymorphism in BDNF
      gene may not confer susceptibility to LOD in Chinese Han population.

PMID- 25384633
TI  - The impact of age at onset of bipolar I disorder on functioning and clinical
      presentation.
AB  - OBJECTIVES: Recent studies have proposed the existence of three distinct
      subgroups of bipolar 1 disorder based on age at onset (AAO). The present study
      aims to investigate potential clinical and functional differences between these
      subgroups in an Australian sample. METHODS: Participants (n = 239) were enrolled
      in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal,
      observational, cross-sectional study. Assessment measures included the Young
      Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical
      Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ
      5D). Participants were also asked about their age at the first major affective
      episode. RESULTS: Three AAO groups were compared: early (AAO < 20, mean = 15.5 +/
      2.72; 44.4% of the participants); intermediate (AAO 20-39, mean = 26.1 +/- 4.8;
      48.14% of the participants) and late (AAO > 40, mean = 50.6 +/- 9.04; 7.4% of the
      participants). Higher rates of depression, suicidal ideation and binge drinking
      were reported by the early AAO group. This group also reported poorer quality of
      life in a number of areas. The early AAO group had a predominant depressive
      initial polarity and the intermediate group had a manic predominance. CONCLUSION:
      Early AAO is associated with an adverse outcome.

PMID- 25384634
TI  - Unilateral neglect in a patient diagnosed with frontotemporal dementia and
      parkinsonism linked to chromosome 17.

PMID- 25384635
TI  - Recurrent unilateral hallucinations in the absence of brain and ear pathology in
      a patient with schizoaffective psychosis and family history of schizophrenia.

PMID- 25384636
TI  - Neighborhood Support and Aging-in-Place Preference Among Low-Income Elderly
      Chinese City-Dwellers.
AB  - OBJECTIVES: Preferences for aging-in-place are unclear among low-income elderly
      Chinese city-dwellers, who are more likely to be geographically bound, to have
      little care support, but possess strong filial values and family cohesiveness.
      This study investigated the preferences for aging-in-place and its contributing
      neighborhood factors among low-income Chinese elderly in a metropolitan city.
      METHOD: We conducted interviews with 400 older people residing in public housing
      estates in Hong Kong. RESULTS: The majority of low-income elderly persons (80.4%)
      prefer to age in place even if their health and functioning has deteriorated
      beyond independent living. Logistic regression showed that (a) having very low
      income (<HK$2,000/month) and not receiving means-tested welfare predicted lower
      preference for this option [odd ratios (OR) = 0.27]; and (b) having medical
      facilities within reach (OR =9.02); and (c) an elderly center in the area (OR =
      2.98) were associated with a preference for aging in place, after controlling for
      demographic, and functioning characteristics. DISCUSSION: Low-income elderly
      Chinese city-dwellers prefer to age in place, given appropriate neighborhood
      support. These findings can be interpreted in light of Lawton's ecological theory
      of aging and suggest a service model similar to the Naturally Occurring
      Retirement Community with Supportive Service Programs.

PMID- 25384637
TI  - The role of attachment style, attachment to therapist, and working alliance in
      response to psychological therapy.
AB  - OBJECTIVES: Working alliance (WA) has been shown to be an important process
      influencing the success of therapy. The association of clients' underlying
      attachment representations with WA and the subsequent success of therapy has
      increasingly been recognized. This study explores the association between adult
      attachment representations, specific attachment to the therapist and WA in
      patients receiving psychological therapy. METHOD: Fifty-eight participants due to
      receive therapy were recruited from primary care psychological services.
      Participants completed self-report measures of attachment, WA, and
      psychopathology. RESULTS: Patients with greater secure attachment to the
      therapist showed significantly greater WA. In a subset of participants completing
      therapy, change in outcome was also correlated with baseline attachment towards
      the therapist. CONCLUSIONS: The study suggests that attachment towards the
      therapist is an important predictor of WA. The results suggest that in terms of
      WA, attachment to the therapist may be more important than pre-existing
      attachment representations. PRACTITIONER POINTS: A more secure attachment to the
      therapist was associated with greater WA and improvement in therapy. Clinicians
      should be mindful of signs of an insecure attachment to themselves, reflecting a
      difficulty around trusting the therapist and viewing them as a secure base.
      Missed sessions and an ongoing reluctance to disclose personal information to the
      therapist may be signs of an insecure attachment. This may be the case even in
      cognitive-behavioural approaches to therapy where relational processes are not
      necessarily a focus of therapy. Incorporating attachment processes in the
      formulation, including attachment to the therapist, may provide one way of
      exploring these issues in therapy.

PMID- 25384638
TI  - The secretome of induced pluripotent stem cells reduces lung fibrosis in part by
      hepatocyte growth factor.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive and
      irreversible fibrotic lung disease, resulting in respiratory insufficiency and
      reduced survival. Pulmonary fibrosis is a result of repeated alveolar epithelial
      microinjuries, followed by abnormal regeneration and repair processes in the
      lung. Recently, stem cells and their secretome have been investigated as a novel
      therapeutic approach in pulmonary fibrosis. We evaluated the potential of induced
      pluripotent stem cells (iPSC) conditioned media (iPSC-cm) to regenerate and
      repair the alveolar epithelium in vitro and improve bleomycin induced lung injury
      in vivo. METHODS: IPSC-cm was collected from cultured iPSC derived from human
      foreskin fibroblasts and its biological effects on alveolar epithelial wound
      repair was studied in an alveolar wound healing assay in vitro. Furthermore, iPSC
      cm was intratracheally instilled 7 days after bleomycin induced injury in the rat
      lungs and histologically and biochemically assessed 7 days after instillation.
      RESULTS: iPSC-cm increased alveolar epithelial wound repair in vitro compared
      with medium control. Intratracheal instillation of iPSC-cm in bleomycin-injured
      lungs reduced the collagen content and improved lung fibrosis in the rat lung in
      vivo. Profibrotic TGFbeta1 and alpha-smooth muscle actin (alpha-sma) expression
      were markedly reduced in the iPSC-cm treated group compared with control.
      Antifibrotic hepatocyte growth factor (HGF) was detected in iPSC-cm in
      biologically relevant levels, and specific inhibition of HGF in iPSC-cm
      attenuated the antifibrotic effect of iPSC-cm, indicating a central role of HGF
      in iPSC-cm. CONCLUSION: iPSC-cm increased alveolar epithelial wound repair in
      vitro and attenuated bleomycin induced fibrosis in vivo, partially due to the
      presence of HGF and may represent a promising novel, cell free therapeutic option
      against lung injury and fibrosis.

PMID- 25384639
TI  - Impairment of shooting performance by background complexity and motion.
AB  - In many visual displays such as virtual environments, human tasks involve objects
      superimposed on both complex and moving backgrounds. However, most studies
      investigated the influence of background complexity or background motion in
      isolation. Two experiments were designed to investigate the joint influences of
      background complexity and lateral motion on a simple shooting task typical of
      video games. Participants had to perform the task on the moving and static
      versions of backgrounds of three levels of complexity, while their eye movements
      were recorded. The backgrounds displayed either an abstract (Experiment 1) or a
      naturalistic (Experiment 2) virtual environment. The results showed that
      performance was impaired by background motion in both experiments. The effects of
      motion and complexity were additive for the abstract background and
      multiplicative for the naturalistic background. Eye movement recordings showed
      that performance impairments reflected at least in part the impact of the
      background visual features on gaze control. 

PMID- 25384640
TI  - Exploring the factors that encourage the illusions of control: the case of
      preventive illusions.
AB  - Most previous research on illusions of control focused on generative scenarios,
      in which participants' actions aim to produce a desired outcome. By contrast, the
      illusions that may appear in preventive scenarios, in which actions aim to
      prevent an undesired outcome before it occurs, are less known. In this
      experiment, we studied two variables that modulate generative illusions of
      control, the probability with which the action takes place, P(A), and the
      probability of the outcome, P(O), in two different scenarios: generative and
      preventive. We found that P(O) affects the illusion in symmetrical, opposite
      directions in each scenario, while P(A) is positively related to the magnitude of
      the illusion. Our conclusion is that, in what concerns the illusions of control,
      the occurrence of a desired outcome is equivalent to the nonoccurrence of an
      undesired outcome, which explains why the P(O) effect is reversed depending on
      the scenario. 

PMID- 25384641
TI  - Desire to work as a death anxiety buffer mechanism.
AB  - Four studies were conducted to examine the death anxiety buffering function of
      work as a terror management mechanism, and the possible moderating role of
      culture. In Study 1, making mortality salient led to higher reports of
      participants' desire to work. In Study 2, activating thoughts of fulfillment of
      the desire to work after mortality salience reduced the accessibility of death
      related thoughts. In Study 3, activating thoughts of fulfillment of the desire to
      work reduced the effects of mortality salience on out-group derogation. In Study
      4, priming thoughts about obstacles to the actualization of desire to work led to
      greater accessibility of death-related thoughts. Although two different cultures
      with contrasting work values were examined, the results were consistent,
      indicating that the desire to work serves as a death anxiety buffer mechanism in
      both cultures. 

PMID- 25384642
TI  - A dual-task paradigm to study the interference reduction in the Simon task.
AB  - Analyzing RT distributions in the Simon task reveals that congruency effects
      decrease for the longest RTs. Four experiments were carried out to examine
      whether this decrease of the congruency effect with response speed was under a
      top-down control or due to bottom-up mechanisms. We specifically manipulated the
      availability of attentional resources by requiring participants to perform a
      Simon task concurrently to different secondary tasks. RT distribution analysis
      (in particular delta functions) was performed under both single-task and dual
      task conditions. Results show that the reduction of the interference effect with
      time could be affected when the Simon task was performed concurrently with a
      secondary task. Nonetheless, the type of the secondary task seems to be a
      critical factor. Therefore, the data suggest that the mechanisms responsible for
      the reduction of the interference effect with time are under some attentional
      control but the exact nature of these mechanisms remains to be explored. 

PMID- 25384644
TI  - The hard fall effect: high working memory capacity leads to a higher, but less
      robust short-term memory performance.
AB  - Participants with a high working memory span tend to perform better than low
      spans in a variety of tasks. However, their performance is paradoxically more
      impaired when they have to perform two tasks at once, a phenomenon that could be
      labeled the "hard fall effect." The present study tested whether this effect
      exists in a short-term memory task, and investigated the proposal that the effect
      is due to high spans using efficient facilitative strategies under simple task
      conditions. Ninety-eight participants performed a spatial short-term memory task
      under simple and dual task conditions; stimuli presentation times either allowed
      for the use of complex facilitative strategies or not. High spans outperformed
      low spans only under simple task conditions when presentation times allowed for
      the use of facilitative strategies. These results indicate that the hard fall
      effect exists on a short-term memory task and may be caused by individual
      differences in strategy use. 

PMID- 25384643
TI  - Audiovisual semantic congruency during encoding enhances memory performance.
AB  - Studies of memory and learning have usually focused on a single sensory modality,
      although human perception is multisensory in nature. In the present study, we
      investigated the effects of audiovisual encoding on later unisensory recognition
      memory performance. The participants were to memorize auditory or visual stimuli
      (sounds, pictures, spoken words, or written words), each of which co-occurred
      with either a semantically congruent stimulus, incongruent stimulus, or a neutral
      (non-semantic noise) stimulus in the other modality during encoding. Subsequent
      memory performance was overall better when the stimulus to be memorized was
      initially accompanied by a semantically congruent stimulus in the other modality
      than when it was accompanied by a neutral stimulus. These results suggest that
      semantically congruent multisensory experiences enhance encoding of both
      nonverbal and verbal materials, resulting in an improvement in their later
      recognition memory. 

PMID- 25384645
TI  - The flip side of the auditory spatial selection benefit: larger attentional
      mixing costs for target selection by ear than by gender in auditory task
      switching.
AB  - In cued auditory task switching, one of two dichotically presented number words,
      spoken by a female and a male, had to be judged according to its numerical
      magnitude. One experimental group selected targets by speaker gender and another
      group by ear of presentation. In mixed-task blocks, the target-defining feature
      (male/female vs. left/right) was cued prior to each trial, but in pure blocks it
      remained constant. Compared to selection by gender, selection by ear led to
      better performance in pure blocks than in mixed blocks, resulting in larger
      "global" mixing costs for ear-based selection. Selection by ear also led to
      larger "local" switch costs in mixed blocks, but this finding was partially
      mediated by differential cue-repetition benefits. Together, the data suggest that
      requirements of attention shifting diminish the auditory spatial selection
      benefit. 

PMID- 25384646
TI  - CME accreditation: separating education from promotion.

PMID- 25384647
TI  - Continued high use of PPIs despite C. difficile risk.

PMID- 25384648
TI  - Controversial sodium guidelines: scientific solution or perpetual debate?

PMID- 25384649
TI  - Suicide rate lower among boys in Iqaluit.

PMID- 25384652
TI  - 10 health stories that mattered: Nov. 1-7.

PMID- 25384650
TI  - Managing the jaundiced newborn: a persistent challenge.

PMID- 25384654
TI  - Imaging in a 35-year-old woman with progressive headache.

PMID- 25384653
TI  - Risk of adverse outcomes among infants of immigrant women according to birth
      weight curves tailored to maternal world region of origin.
AB  - BACKGROUND: Infants of immigrant women in Western nations generally have lower
      birth weights than infants of native-born women. Whether this difference is
      physiologic or pathological is unclear. We determined whether the use of birth
      weight curves tailored to maternal world region of origin would discriminate
      adverse neonatal and obstetric outcomes more accurately than a single birth
      weight curve based on infants of Canadian-born women. METHODS: We performed a
      retrospective cohort study of in-hospital singleton live births (328,387 to
      immigrant women, 761,260 to nonimmigrant women) in Ontario between 2002 and 2012
      using population health services data linked to the national immigration
      database. We classified infants as small for gestational age (<10th percentile)
      or large for gestational age (>=90th percentile) using both Canadian and world
      region-specific birth-weight curves and compared associations with adverse
      neonatal and obstetric outcomes. RESULTS: Compared with world region-specific
      birth-weight curves, the Canadian curve classified 20 431 (6.2%) additional
      newborns of immigrant women as small for gestational age, of whom 15,467 (75.7%)
      were of East or South Asian descent. The odds of neonatal death were lower among
      small-for-gestational-age infants of immigrant women than among those of
      nonimmigrant women based on the Canadian birth-weight curve (adjusted odds ratio
      [OR] 0.83, 95% confidence interval [CI] 0.72-0.95), but higher when small for
      gestational age was defined by the world region-specific curves (adjusted OR
      1.24, 95% CI 1.08-1.42). Conversely, the odds of some adverse outcomes were lower
      among large-for-gestational-age infants of immigrant women than among those of
      nonimmigrant women based on world region-specific birth-weight curves, but were
      similar based on the Canadian curve. INTERPRETATION: World region-specific birth
      weight curves seemed to be more appropriate than a single Canadian population
      based curve for assessing the risk of adverse neonatal and obstetric outcomes
      among small- and large-for-gestational-age infants born to immigrant women,
      especially those from the East and South Asian regions.

PMID- 25384655
TI  - Screening with the Pap test.

PMID- 25384656
TI  - Gairdner presents cutting-edge cancer research.

PMID- 25384658
TI  - Expression of special AT-rich sequence-binding protein 1 is an independent
      prognostic factor in cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) is a group of slowly progressive,
      lymphoproliferative disorders characterized by localization of neoplastic T
      lymphocytes to the skin. The most common type of CTCL is mycosis fungoides which
      has a mild clinical course with slow and long progression. The rate of
      progression is generally slow and takes many years but often remains
      unpredictable. Special AT-rich sequence-binding protein-1 (SATB1) is a global
      chromatin organizer which controls gene expression by folding and remodeling
      chromatin, but which also regulates the level of histone methylation and
      acetylation, important in differentiation and apoptosis. The aim of the present
      study was to determine if SATB1 may be considered a prognostic and predictive
      factor of CTCL. The results showed that moderate and high expression of SATB1
      correlate with significantly better prognosis of CTCL patients. Moreover, we
      showed that downregulation of SATB1 in Jurkat cells caused their resistance to
      activation-induced cell death. In conclusion, SATB1 expression appears to be a
      strong candidate as a prognostic factor confirming the inner heterogeneous
      features of CTCLs.

PMID- 25384659
TI  - Persister cells in biofilm associated infections.

PMID- 25384660
TI  - Fungal biofilms in human disease.

PMID- 25384661
TI  - Biofilm-infected pressure ulcers: current knowledge and emerging treatment
      strategies.

PMID- 25384662
TI  - Microbial biofilms and adverse reactions to gel fillers used in cosmetic surgery.

PMID- 25384663
TI  - Role of biofilms in breast implant associated infections and capsular
      contracture.

PMID- 25384664
TI  - Innovative strategies for combating biofilm-based infections.

PMID- 25384665
TI  - Antimicrobial polymers for anti-biofilm medical devices: state-of-art and
      perspectives.

PMID- 25384666
TI  - Antimicrobial photodynamic therapy for treatment of biofilm-based infections.

PMID- 25384667
TI  - Anti-biofilm agents in control of device-related infections.

PMID- 25384668
TI  - Lipid- and polymer-based drug delivery carriers for eradicating microbial
      biofilms causing medical device-related infections.

PMID- 25384669
TI  - Transcriptome response of Lactobacillus sakei to meat protein environment.
AB  - Lactobacillus sakei is a heterofermentative species of lactic acid bacteria that
      is used in industrial meat fermentation. To investigate adaptation in a meat
      environment, whole-genome DNA microarrays were used to analyze the gene
      expression related to growth and survival of L. sakei strain La22 when grown in
      sarcoplasmic (S-) or myofibrillar (M-) protein-supplemented chemically defined
      medium (CDM). Differential expression was detected in 551 genes. Genes encoding
      enzymes involved in peptide hydrolysis were differentially upregulated in M-CDM
      or/and S-CDM, and only oppB and oppC, involved in the amino acid and peptide
      transport system, were upregulated. Most genes related to metabolism of peptides,
      amino acids and related molecules were over-expressed in M-CDM and S-CDM, except
      for glnA and metK. Expression of certain genes was according to the differential
      substrate environment. The expression of genes involved in the stress response
      was not induced by growth in M-CDM. 

PMID- 25384671
TI  - Time trends in incidence, clinical features, and cardiovascular disease in
      ankylosing spondylitis over three decades: a population-based study.
AB  - OBJECTIVE: To determine trends in the incidence and clinical presentation of
      ankylosing spondylitis (AS), the incidence of cardiovascular disease (CVD), and
      cardiovascular (CV) risk factors among patients with AS and compare the observed
      incidence of CVD with that predicted by the Framingham Risk Score (FRS). METHODS:
      A population-based inception cohort of residents of Olmsted County, Minnesota age
      >=18 years who fulfilled Modified New York Criteria for AS in 1980-2009 was
      assembled. Clinical features at presentation were recorded. Age- and sex-adjusted
      incidence rates and survival were estimated. Incident CVD and CV risk factors
      were identified. The 10-year CVD risk was calculated using the FRS. Standardized
      incidence ratios (ratios of observed CVD in AS to that predicted by the FRS) were
      calculated. RESULTS: Eighty-six patients were diagnosed with AS over the study
      period with an age- and sex-adjusted incidence of 3.1 per 100,000 (95% confidence
      interval [95% CI] 2.5-3.8). The mean age at diagnosis was 35 years (range 19-69
      years). Inflammatory back pain, seen in 90% of patients, was the most common
      presenting manifestation. The 10-year mean +/- SD cumulative incidence of CVD was
      15.8% +/- 6.1%, three times higher than the predicted events based on the FRS
      (standardized incidence ratio 3.01, 95% CI 1.35-6.69; P = 0.007). Overall
      survival was similar to the general population. CONCLUSION: AS occurs in
      approximately 3 persons per 100,000 per year. Clinical features, extraarticular
      manifestations, and interval from symptom onset to diagnosis have remained
      constant in this population over the study period. The CVD risk in these patients
      is higher than expected and underestimated by the FRS.

PMID- 25384670
TI  - The staphylococcal toxins gamma-haemolysin AB and CB differentially target
      phagocytes by employing specific chemokine receptors.
AB  - Evasion of the host phagocyte response by Staphylococcus aureus is crucial to
      successful infection with the pathogen. gamma-haemolysin AB and CB (HlgAB, HlgCB)
      are bicomponent pore-forming toxins present in almost all human S. aureus
      isolates. Cellular tropism and contribution of the toxins to S. aureus
      pathophysiology are poorly understood. Here we identify the chemokine receptors
      CXCR1, CXCR2 and CCR2 as targets for HlgAB, and the complement receptors C5aR and
      C5L2 as targets for HlgCB. The receptor expression patterns allow the toxins to
      efficiently and differentially target phagocytic cells. Murine neutrophils are
      resistant to HlgAB and HlgCB. CCR2 is the sole murine receptor orthologue
      compatible with gamma-haemolysin. In a murine peritonitis model, HlgAB
      contributes to S. aureus bacteremia in a CCR2-dependent manner. HlgAB-mediated
      targeting of CCR2(+) cells highlights the involvement of inflammatory macrophages
      during S. aureus infection. Functional quantification identifies HlgAB and HlgCB
      as major secreted staphylococcal leukocidins. 

PMID- 25384672
TI  - Saffron (Crocus sativus) for depression: a systematic review of clinical studies
      and examination of underlying antidepressant mechanisms of action.
AB  - BACKGROUND: Saffron, a spice derived from the flower of Crocus sativus, has now
      undergone several trials examining its antidepressant effects and, in a recent
      meta-analysis, was confirmed to be effective for the treatment of major
      depression. OBJECTIVE: To provide an expanded systematic analysis of the
      completed clinical studies on saffron and depression, detailing dosages, extract
      sources, standardisations, safety profile and treatment duration; and, through a
      narrative review, to examine its potential antidepressant mechanisms of action.
      DESIGN: In the systematic review of clinical trials, electronic databases were
      searched for high-quality, randomised, double-blind studies, with placebo or
      antidepressant controls. A narrative review of in vivo and in vitro studies was
      conducted to examine its potential antidepressant mechanisms of action. RESULTS:
      In the systematic review, six studies were identified. In the placebo-comparison
      trials, saffron had large treatment effects and, when compared with
      antidepressant medications, had similar antidepressant efficacy. Saffron's
      antidepressant effects potentially are due to its serotonergic, antioxidant, anti
      inflammatory, neuro-endocrine and neuroprotective effects. CONCLUSIONS: Research
      conducted so far provides initial support for the use of saffron for the
      treatment of mild-to-moderate depression. Further research is required to expand
      our understanding of the role and actions of saffron in major depression.

PMID- 25384675
TI  - Solvent effects on the intramolecular conversion of trimethylsulfonium chloride
      to dimethyl sulfide and methyl chloride.
AB  - The formation of CH3Cl from (CH3)3SCl in various solvents has been studied based
      on M05/6-311+G(2d,p) DFT calculations to quantify the influence of the solvent on
      the stability of sulfonium cations. Four different pathways (one SN1, one
      backside and two frontside attacks for SN2) as well as the formation of different
      ion pairs (tripod, seesaw, and linear) are discussed to investigate the origin of
      the kinetic solvent effect (KSE) and the contribution of ion pairs to the overall
      reaction. Ion pairs are formed only in solvents with a permittivity epsilon lower
      than 28, but the reaction proceeds via a standard SN2 mechanism with a backside
      attack in all solvents. The formation of ion pairs does not change the order of
      the rate law, but it strongly influences the KSE, which can distinguish between
      reactions starting from free ions and those starting from ion pairs, in contrast
      to standard kinetic analysis. 

PMID- 25384676
TI  - Ki67 is a promising molecular target in the diagnosis of cancer (review).
AB  - The expression of Ki67 is strongly associated with tumor cell proliferation and
      growth, and is widely used in routine pathological investigation as a
      proliferation marker. The nuclear protein Ki67 (pKi67) is an established
      prognostic and predictive indicator for the assessment of biopsies from patients
      with cancer. Clinically, pKi67 has been shown to correlate with metastasis and
      the clinical stage of tumors. In addition, it has been shown that Ki67 expression
      is significantly higher malignant tissues with poorly differentiated tumor cells,
      as compared with normal tissue. According to its predictive role, pKi67
      expression identifies subpopulations of patients who are more likely to respond
      to a given therapy. The Ki67 labeling index is an independent prognostic factor
      for survival rate, which includes all stages and grade categories. There is a
      correlation between the ratio of Ki67-positive malignant cells and patient
      survival. It has been shown that blocking of Ki67 either by microinjection of
      antibodies or through the use of antisense oligonucleotides leads to the arrest
      of cell proliferation. Specifically, antisense oligonucleotides and antibodies
      against pKi67 have been shown to inhibit the progression of the cell cycle. The
      Ki67 protein is well characterized at the molecular level and is extensively used
      as a prognostic and predictive marker for cancer diagnosis and treatment.
      Increasing evidence indicates that Ki67 may be an effective target in cancer
      therapy. It therefore merits further development, including testing in more
      sophisticated in vitro and appropriate in vivo models. This review provides an
      overview of recent advances in this field.

PMID- 25384674
TI  - S3 guideline on psychosocial therapies in severe mental illness: evidence and
      recommendations.
AB  - The burden of severe and persistent mental illness is high. Beside somatic
      treatment and psychotherapeutic interventions, treatment options for patients
      with severe mental illness also include psychosocial interventions. This paper
      summarizes the results of a number of systematic literature searches on
      psychosocial interventions for people with severe mental illness. Based on this
      evidence appraisal, recommendations for the treatment of people with severe
      mental illness were formulated and published in the evidence-based guideline
      series of the German Society for Psychiatry, Psychotherapy and Neurology (DGPPN)
      as an evidence-based consensus guideline ("S3 guideline"). Recommendations were
      strongly based on study results, but used consensus processes to consider
      external validity and transferability of the recommended practices to the German
      mental healthcare system. A distinction is made between system-level
      interventions (multidisciplinary team-based psychiatric community care, case
      management, vocational rehabilitation and participation in work life and
      residential care interventions) and single psychosocial interventions
      (psychoeducation, social skills training, arts therapies, occupational therapy
      and exercise therapy). There is good evidence for the efficacy of the majority of
      psychosocial interventions in the target group. The best available evidence
      exists for multidisciplinary team-based psychiatric community care, family
      psychoeducation, social skills training and supported employment. The present
      guideline offers an important opportunity to further improve health services for
      people with severe mental illness in Germany. Moreover, the guideline highlights
      areas for further research. 

PMID- 25384677
TI  - Spatial patterns of close relationships across the lifespan.
AB  - The dynamics of close relationships is important for understanding the migration
      patterns of individual life-courses. The bottom-up approach to this subject by
      social scientists has been limited by sample size, while the more recent top-down
      approach using large-scale datasets suffers from a lack of detail about the human
      individuals. We incorporate the geographic and demographic information of
      millions of mobile phone users with their communication patterns to study the
      dynamics of close relationships and its effect in their life-course migration. We
      demonstrate how the close age- and sex-biased dyadic relationships are correlated
      with the geographic proximity of the pair of individuals, e.g., young couples
      tend to live further from each other than old couples. In addition, we find that
      emotionally closer pairs are living geographically closer to each other. These
      findings imply that the life-course framework is crucial for understanding the
      complex dynamics of close relationships and their effect on the migration
      patterns of human individuals. 

PMID- 25384678
TI  - p53 suppresses 14-3-3gamma by stimulating proteasome-mediated 14-3-3gamma protein
      degradation.
AB  - 14-3-3 proteins are a family of highly conserved polypeptides that interact with
      a large number of proteins and play a role in a wide variety of cellular
      processes. 14-3-3 proteins have been demonstrated overexpressed in several
      cancers and serving as potential oncogenes. In a previous study we showed one
      isoform of the 14-3-3 family, 14-3-3gamma was negatively regulated by p53 through
      binding to its promoter and inhibiting its transcription. In the present study we
      investigated both p53 and 14-3-3gamma protein levels in human lung cancerous
      tissues and normal lung tissues. We found 14-3-3gamma expression correlated to
      p53 overexpression in lung cancer tissues. Ecotopic expression of wild-type p53,
      but not mutant p53 (R175H) suppressed both endogenous and exogenous 14-3-3gamma
      in colon and lung cancer cell lines. Further examination demonstrated that p53
      interacted with C-terminal domain of 14-3-3gamma and induced 14-3-3gamma
      ubiquitination. MG132, a specific inhibitor of the 26S proteasome, could block
      the effect of p53 on 14-3-3gamma protein levels, suggesting that p53 suppressed
      14-3-3gamma by stimulating the process of proteasome-mediated degradation of 14-3
      3gamma. These results indicate that the inhibitory effect of p53 on 14-3-3gamma
      is mediated also by a post-transcriptional mechanism. Loss of p53 function may
      result in upregulation of 14-3-3gamma in lung cancers. 

PMID- 25384679
TI  - High-performance asymmetric supercapacitors based on multilayer MnO2 /graphene
      oxide nanoflakes and hierarchical porous carbon with enhanced cycling stability.
AB  - In this work, MnO(2)/GO (graphene oxide) composites with novel multilayer
      nanoflake structure, and a carbon material derived from Artemia cyst shell with
      genetic 3D hierarchical porous structure (HPC), are prepared. An asymmetric
      supercapacitor has been fabricated using MnO(2)/GO as positive electrode and HPC
      as negative electrode material. Because of their unique structures, both
      MnO(2)/GO composites and HPC exhibit excellent electrochemical performances. The
      optimized asymmetric supercapacitor could be cycled reversibly in the high
      voltage range of 0-2 V in aqueous electrolyte, which exhibits maximum energy
      density of 46.7 Wh kg(-1) at a power density of 100 W kg(-1) and remains 18.9 Wh
      kg(-1) at 2000 W kg(-1). Additionally, such device also shows superior long cycle
      life along with ~100% capacitance retention after 1000 cycles and ~93% after 4000
      cycles.

PMID- 25384681
TI  - Associations of resting-state fMRI functional connectivity with flow-BOLD
      coupling and regional vasculature.
AB  - There has been tremendous interest in applying functional magnetic resonance
      imaging-based resting-state functional connectivity (rs-fcMRI) measurements to
      the study of brain function. However, a lack of understanding of the
      physiological mechanisms of rs-fcMRI limits their ability to interpret rs-fcMRI
      findings. In this work, the authors examine the regional associations between rs
      fcMRI estimates and dynamic coupling between the blood oxygenation level
      dependent (BOLD) and cerebral blood flow (CBF), as well as resting macrovascular
      volume. Resting-state BOLD and CBF data were simultaneously acquired using a dual
      echo pseudocontinuous arterial spin labeling (pCASL) technique, whereas
      macrovascular volume fraction was estimated using time-of-flight MR angiography.
      Functional connectivity within well-known functional networks-including the
      default mode, frontoparietal, and primary sensory-motor networks-was calculated
      using a conventional seed-based correlation approach. They found the functional
      connectivity strength to be significantly correlated with the regional increase
      in CBF-BOLD coupling strength and inversely proportional to macrovascular volume
      fraction. These relationships were consistently observed within all functional
      networks considered. Their findings suggest that highly connected networks
      observed using rs-fcMRI are not likely to be mediated by common vascular drainage
      linking distal cortical areas. Instead, high BOLD functional connectivity is more
      likely to reflect tighter neurovascular connections, attributable to neuronal
      pathways.

PMID- 25384682
TI  - Commonalities and challenges in the development of clinical trial measures in
      neurology.
AB  - As neurologists and neuroscientists, we are trained to evaluate disorders of the
      nervous system by thinking systematically. Clinically, we think in terms of
      cognition, behavior, motor function, sensation, balance and co-ordination, and
      autonomic system function. But when we assess symptoms of neurological disorders
      for the purpose of drug development, we tend to create disease-specific outcome
      measures, often using a variety of methods to assess the same types of
      dysfunction in overlapping, related disorders. To begin to explore the potential
      to simplify and harmonize the assessment of dysfunction across neurological
      disorders, a symposium, entitled, "Commonalities in the Development of Outcome
      Measures in Neurology" was held at the 16th annual meeting of the American
      Society for Experimental NeuroTherapeutics (ASENT), in February 2014. This paper
      summarizes the presentations at the symposium. The authors hope that readers will
      begin to view Clinical Outcome Assessment (COA) development in a new light. We
      hope that in presenting this material, we will stimulate discussions and
      collaborations across disease areas to develop common concepts of neurological
      COA development and construction. 

PMID- 25384683
TI  - Tailoring nanoscale properties of tungsten oxide for inkjet printed
      electrochromic devices.
AB  - This paper focuses on the engineering procedures governing the synthesis of
      tungsten oxide nanocrystals and the formulation of printable dispersions for
      electrochromic applications. By that means, we aim to stress the relevancy of a
      proper design strategy that results in improved physicochemical properties of
      nanoparticle loaded inks. In the present study inkjet printable nanostructured
      tungsten oxide particles were successfully synthesized via hydrothermal processes
      using pure or acidified aqueous sol-gel precursors. Based on the proposed scheme,
      the structure and morphology of the nanoparticles were tailored to ensure the
      desired printability and electrochromic performance. The developed nanomaterials
      with specified structures effectively improved the electrochemical response of
      printed films, resulting in 2.5 times higher optical modulation and 2 times
      faster coloration time when compared with pure amorphous films.

PMID- 25384684
TI  - Teaching graphic symbol combinations to children with limited speech during
      shared story reading.
AB  - The aim of this study was to determine the effect of an intervention strategy on
      the production of graphic symbol combinations in children with limited speech.
      Four children between the ages of 6;5 and 10;8 (years;months) with limited speech
      participated in the study. A single-subject, multiple probe design across three
      different types of semantic relations was used. Generalization to untrained
      exemplars was also monitored. Results were mixed across the four participants:
      two participants learned to combine symbols across different types of relations,
      maintained these skills post intervention, and generalized their skills to
      untrained combinations; and two participants showed less consistent evidence of
      learning. The effects, as measured during structured probes, were strong for one
      participant, moderate for another, and inconclusive for the two others. Responses
      during shared story reading suggested that the measurement probes might have
      underestimated participants' ability to combine symbols.

PMID- 25384685
TI  - 3D bioprinting of biomimetic aortic vascular constructs with self-supporting
      cells.
AB  - Cardiovascular diseases are the leading cause of deaths throughout the world.
      Vascular diseases are mostly treated with autografts and blood vessel
      transplantations. However, traditional grafting methods have several problems
      including lack of suitable harvest sites, additional surgical costs for
      harvesting procedure, pain, infection, lack of donors, and even no substitutes at
      all. Recently, tissue engineering and regenerative medicine approaches are used
      to regenerate damaged or diseased tissues. Most of the tissue engineering
      investigations have been based on the cell seeding into scaffolds by providing a
      suitable environment for cell attachment, proliferation, and differentiation.
      Because of the challenges such as difficulties in seeding cells spatially,
      rejection, and inflammation of biomaterials used, the recent tissue engineering
      studies focus on scaffold-free techniques. In this paper, the development of
      novel computer aided algorithms and methods are developed for 3D bioprinting of
      scaffold-free biomimetic macrovascular structures. Computer model mimicking a
      real human aorta is generated using imaging techniques and the proposed
      computational algorithms. An optimized three-dimensional bioprinting path
      planning are developed with the proposed self-supported model. Mouse embryonic
      fibroblast (MEF) cell aggregates and support structures (hydrogels) are 3D
      bioprinted layer-by-layer according to the proposed self-supported method to form
      an aortic tissue construct.

PMID- 25384686
TI  - An observational, longitudinal study on the home environment of people with
      chronic obstructive pulmonary disease: the research protocol of the Home Sweet
      Home study.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) represents an
      important public health challenge. Patients are confronted with limitations
      during activities of daily living (ADLs). Resident loved ones of patients with
      COPD may be uniquely positioned to witness these limitations. COPD may have an
      impact on not only the patients' life, but also on the lives of the resident
      loved ones. Furthermore, COPD exacerbation-related hospital admissions often
      occur in patients with COPD. However, whether and to what extent these admissions
      influence resident loved ones' burden and health status remains currently
      unknown. Therefore, the primary objectives of this study are to investigate the
      differences between patients with COPD and resident loved ones' perceptions of
      patients' health status and problematic ADLs and to study prospectively the
      effects of a COPD exacerbation on resident loved ones' perceptions of patients'
      health status and problematic ADLs. METHODS AND ANALYSIS: An observational,
      longitudinal study will be performed in 192 patients with COPD and their 192
      resident loved ones. Primary outcomes are daily functioning, ADL, disease
      specific health status, generic health status and dyspnoea. These will be
      assessed during home visits at baseline and after 12 months. Additional home
      visits will be performed when a COPD exacerbation-related hospital admission
      occurs during the 12-month follow-up period. ETHICS AND DISSEMINATION: This
      protocol was approved by the Medical Ethics Committee of the Catharina Hospital
      Eindhoven, the Netherlands (NL42721.060.12/M12-1280) and is registered in the
      Dutch Trial Register (NTR3941).

PMID- 25384687
TI  - Population-based cohort study on the risk of pneumonia in patients with non
      traumatic intracranial haemorrhage who use proton pump inhibitors.
AB  - OBJECTIVES: This nationwide cohort study investigated the association between
      proton pump inhibitor (PPI) usage and the risk of pneumonia in patients with non
      traumatic intracranial haemorrhage (ICH). DESIGN: Nationwide population-based
      cohort study. SETTING: Longitudinal Health Insurance Database 2010 (LHID2010)
      sampled from the Taiwan National Health Insurance Research Database.
      PARTICIPANTS: 4644 patients with non-traumatic ICH from 2010 to 2011 were
      identified. Patients aged <18 years and newly diagnosed with non-traumatic ICH
      complicated with pneumonia during the same admission period were excluded. A
      total of 2170 participants were eligible for the final analysis. MAIN OUTCOME
      MEASURE: Patients using PPIs or not during the study period were tracked to
      identify the occurrence of any type of pneumonia. RESULTS: The adjusted HR of the
      risk of pneumonia for ICH patients who used PPIs was 1.61 (95% CI 1.32 to 1.97,
      p<0.001). The risk of pneumonia was positively associated with the administration
      of PPIs. We observed a greater risk of pneumonia in patients who used PPIs than
      in those who did not. Moreover, we observed that the risk of pneumonia in
      patients who used PPIs was 2.60 and 2.04 (95% CI 2.01 to 3.38, p<0.001; 95% CI
      1.34 to 3.10, p<0.001) greater than that in patients who did not use PPIs when
      the defined daily dose was <30 and 30-60, respectively. CONCLUSIONS: The results
      of this study indicate that the use of PPIs in patients with non-traumatic ICH is
      associated with an increased risk of pneumonia, and the severity of this risk
      depends on the defined daily dose. Physicians should exercise caution when
      prescribing PPIs for patients with non-traumatic ICH.

PMID- 25384688
TI  - Prevalence of insomnia and its clinical correlates in a general population in
      Turkey.
AB  - AIM: The prevalence of insomnia is influenced by environmental factors. This
      study aimed to investigate the prevalence of insomnia and its sociodemographic
      and clinical correlates in a general population-based survey in Turkey. METHODS:
      This population-based study included 4758 subjects among 5021 who participated in
      the Turkish Adult Population Epidemiology of Sleep Disorders study. Questionnaire
      items evaluating insomnia were adapted from the International Classification of
      Sleep Disorders II and the DSM-IV-TR. Subjects with restless legs syndrome were
      excluded. RESULTS: Insomnia was found to be associated with older age (18-24
      years, 9.8%; 25-44 years, 11.7%; 45-64 years, 13.8%; 65 years or older, 13.9%),
      lower income level (<500 USD, 16.5%), time spent watching TV (6-8 h or more,
      18.4%), tea consumption in the evening (>=6 glasses, 14.5%) and smoking status
      (current and ex-smoker, both 14.2%) in multiple logistic regression analysis. In
      respect to other medical disorders, insomnia was significantly associated with
      the presence of hypertension, diabetes and heart diseases after the adjustment
      for relevant risk factors for each disease, across all age and sex groups.
      CONCLUSIONS: Insomnia is a major health problem in our population, affecting
      subjects in the working age group and those of lower socioeconomic status. It
      should especially be screened in patients with chronic diseases. A relatively low
      proportion of insomnia diagnosed as a sleep disorder suggests that this condition
      and its clinical correlates are possibly under-recognized.

PMID- 25384689
TI  - Weekly use of fluconazole as prophylaxis in haematological patients at risk for
      invasive candidiasis.
AB  - BACKGROUND: The goal was to determine whether one medical centres' unique
      antifungal prophylactic regimen for patients at high risk for invasive
      candidiasis because of their haematological malignancies, haematopoietic stem
      cell transplants, or high-dose chemotherapy might lead ultimately to a higher
      incidence of infection, to increasing fluconazole resistance, or to a shift in
      the predominant strain of Candida in invasive fungal episodes. METHODS: Data were
      collected retrospectively, for a ten-year period from ONKO-KISS surveillance
      records, and from hospital, medical, and pharmacy records and then evaluated with
      respect to incidence of fungal infection episodes, emergence of antifungal drug
      resistance, and predominance of specific Candida strains in isolate cultures.
      Fisher's exact test and linear regression were used to compare minimum inhibitory
      concentrations and to compare the incidence of different Candida isolates,
      respectively. RESULTS: The incidence of infection remained quite stable over 10
      years with a median of 0.67 episodes/1000 bed days. Overall, Candida glabrata was
      the predominant species with 29% followed by C. albicans and C. krusei (14%
      each). No significant increment of non-albicans Candida species with decreased
      fluconazole susceptibility was perceived over this decade. CONCLUSIONS: Once
      weekly administration of 400 mg of fluconazole to prevent candidaemia appears to
      have no negative impact on the efficacy as a prophylaxis when compared to
      standard of care (400 mg of fluconazole daily).

PMID- 25384690
TI  - Preoperative autonomic nervous system analysis may stratify the risk of
      hypotension after spinal anesthesia.
AB  - BACKGROUND: Studies on pregnant women undergoing cesarean delivery or elderly men
      scheduled for prostate brachytherapy have demonstrated the predictive value of
      heart rate variability (HRV) analysis for hypotension during spinal anesthesia.
      We conducted a prospective observational study to investigate if preoperative HRV
      analysis may have a role in identifying the risk of hypotension following spinal
      anesthesia in otherwise healthy patients. METHODS: The study investigated 47 ASA
      physical status I-II patients aged between 18-50 years that underwent
      subarachnoid anesthesia for lower abdominal or orthopedic scheduled surgery. ECG
      was recorded from all subjects before the subarachnoid block. We analysed the
      autonomic nervous system modulation, measured by HRV analysis. The variables that
      were be considered were preoperative HRV total power, low frequency (LF) and high
      frequency (HF) heart beat oscillations and LF/HF ratio. The LF/HF ratio was
      dichotomized according to the median for sensitivity analysis. The lowest
      arterial pressure value between spinal anesthesia and the end of surgery was
      recorded. RESULTS: The median LF/HF before anesthesia was 2.3. We considered two
      groups of 23 (LF/HF<2.3, group LOW) and 24 (LF/HF>2.3, group HIGH) patients
      respectively. Both groups had similar baseline demographic and hemodynamic
      variables. A high preoperative sympathetic outflow and loss of vagal modulation,
      as stated by LF/HF>2.3, was correlated with a relative risk of 7.7 (95%CI 1.04 to
      56.6, p=0.023) of post-spinal hypotension. CONCLUSIONS: Preoperative analysis of
      autonomic nervous system modulation might be useful to stratify the risk of post
      spinal hypotension and it might indicate the need for careful monitoring or
      prophylactic fluids.

PMID- 25384691
TI  - Vasopressin in cirrhosis and sepsis: physiology and clinical implications.
AB  - Arginine-vasopressin (AVP) is an important hormone in the regulation of plasma
      osmolality and blood volume/pressure. In clinical practice it is frequently used
      in the treatment of septic shock and decompensated cirrhosis. In this review the
      physiology of AVP and its analogues is presented. In addition the use of AVP in
      cirrhosis and sepsis is reviewed. 

PMID- 25384692
TI  - Evidence of peripheral nerve blocks for cancer-related pain: a systematic review.
AB  - The European Association for Palliative Care has initiated a comprehensive
      program to achieve an over-all review of the evidence of multiple cancer pain
      management strategies in order to extend the current guideline for treatment of
      cancer pain. The present systematic review analyzed the existing evidence of
      analgesic efficacy for peripheral nerve blocks in adult patients with cancer. A
      search strategy was elaborated with words related to cancer, pain, peripheral
      nerve and block. The search was performed in PubMed, EMBASE, and Cochrane for the
      period until February 2014. The number of abstracts retrieved was 155. No
      controlled studies were identified. Sixteen papers presented a total of 79 cases.
      The blocks applied were paravertebral blocks (10 cases), blocks in the head
      region (2 cases), plexus blocks (13 cases), intercostal blocks (43 cases) and
      others (11 cases). In general, most cases reported good pain relief and no side
      effects. The use of peripheral blocks is based upon anecdotal evidence. However,
      this review only demonstrates the lack of studies, which does not equal a lack of
      effectiveness. 

PMID- 25384693
TI  - Revised ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and
      management. Implications for preoperative clinical evaluation.
AB  - Each year, an increasing number of elderly patients with cardiovascular disease
      undergoing non-cardiac surgery require careful perioperative management to
      minimize the perioperative risk. Perioperative cardiovascular complications are
      the strongest predictors of morbidity and mortality after major non-cardiac
      surgery. A Joint Task Force of the European Society of Cardiology (ESC) and the
      European Society of Anaesthesiology (ESA) has recently published revised
      Guidelines on the perioperative cardiovascular management of patients scheduled
      to undergo non-cardiac surgery, which represent the official position of the ESC
      and ESA on various aspects of perioperative cardiac care. According to the
      Guidelines effective perioperative cardiac management includes preoperative risk
      stratification based on preoperative assessment of functional capacity, type of
      surgery, cardiac risk factors, and cardiovascular function. The ESC/ESA
      Guidelines discourage indiscriminate routine preoperative cardiac testing,
      because it is time- and cost-consuming, resource-limiting, and does not improve
      perioperative outcome. They rather emphasize the importance of individualized
      preoperative cardiac evaluation and the cooperation between anesthesiologists and
      cardiologists. We summarize the relevant changes of the 2014 Guidelines as
      compared to the previous ones, with particular emphasis on preoperative cardiac
      testing. 

PMID- 25384694
TI  - Meal types as sources for intakes of fruits, vegetables, fish and whole grains
      among Norwegian adults.
AB  - OBJECTIVE: To study how different meals contribute to intakes of fruits,
      vegetables, fish and whole grains in a group of Norwegian adults and in subgroups
      of this population. Moreover, to investigate the consequences of skipping the
      meal contributing most to the intake of each food group (main contributing meal).
      DESIGN: Cross-sectional dietary survey in Norwegian adults. Dietary data were
      collected using two non-consecutive telephone-administered 24 h recalls. The
      recorded meal types were breakfast, lunch, dinner, supper/evening meal and
      snacks. SETTING: Nationwide, Norway (2010-2011). SUBJECTS: Adults aged 18-70
      years (n 1787). RESULTS: Dinner was the main contributing meal for fish and
      vegetables, while snacks were the main contributing meal for fruit intake. For
      whole grains, breakfast was the main contributing meal. The main contributing
      meal did not change for any of the food groups when studying subgroups of the
      participants according to intake of each food group, educational level or age. A
      substantially lower intake of the food groups in question was found on days when
      the main contributing meal was skipped. CONCLUSIONS: Intakes of fruits,
      vegetables, fish and whole grains largely depend on one meal type. Inclusion of
      these foods in other meals in addition to the main contributing meal, preferably
      replacing energy-dense nutrient-poor foods, should be promoted.

PMID- 25384695
TI  - Bioleaching of multiple heavy metals from contaminated sediment by mesophile
      consortium.
AB  - A defined mesophile consortium including Acidithiobacillus ferrooxidans,
      Acidithiobacillus thiooxidans, and Leptospirilum ferriphilum was applied in
      bioleaching sediments contaminated with multiple heavy metals. Flask experiments
      showed that sulfur favored the acidification in the early stage while pyrite led
      to a great acidification potential in the later stage. An equal sulfur/pyrite
      ratio got the best acidification effect. Substrate utilization started with
      sulfur in the early stage, and then the pH decline and the community shift give
      rise to the utilization of pyrite. Solubilization efficiency of Zn, Cu, Mn, and
      Cd reached 96.1, 93.3, 92.13, and 87.65%, respectively. Bioleaching efficiency of
      other elements (As, Hg, Pb) was not more than 30%. Heavy metal solubilization was
      highly negatively correlated with pH variation. Logistic models were well fitted
      with the solubilization efficiency, which can be used to predict the bioleaching
      process. The dominant species in the early stage of bioleaching were A.
      ferrooxidans and A. thiooxidans, and the abundance of L. ferriphilum increased
      together with pyrite utilization and pH decline.

PMID- 25384696
TI  - Health risk assessment of organochlorine pesticide exposure through dietary
      intake of vegetables grown in the periurban sites of Delhi, India.
AB  - The study investigated the levels of organochlorine pesticides (OCPs) in
      different types of vegetables grown in periurban area of National Capital Region
      (NCR), India. Vegetable sampling was carried out in winter and summer season of
      2012. A total of 20 different OCPs were determined using gas chromatography (GC)
      assembled with electron capture detector (ECD). Obtained results showed that
      average levels of ?(20)OCP ranged from 83.8 +/- 25.5 ng g(-1) in smooth gourd to
      222.4 +/- 90.0 ng g(-1) in cauliflower. The mean concentrations of different OCPs
      were observed in order of ?HCH > ?CHLs > drins > ?endosulfan > ?DDT in all
      vegetables except in brinjal and smooth gourd. Most of the OCP residues recorded
      in vegetable samples exceeded the maximum residue levels (MRLs) set by
      international and national regulatory agencies. Health risk assessment suggests
      that daily dietary OCP exposure via vegetable consumption was higher for children
      (mean value 4.25E-05) than adults (mean value 2.19E-05). The hazard quotient (HQ)
      and lifetime cancer risk (LCR) estimated from dietary exposure of these
      vegetables were above the acceptable limit and can be considered as a serious
      concern for Delhi population.

PMID- 25384697
TI  - The responsiveness, content validity, and convergent validity of the Measure
      Yourself Concerns and Wellbeing (MYCaW) patient-reported outcome measure.
AB  - OBJECTIVE: Measure Yourself Concerns and Wellbeing (MYCaW) is a patient-centered
      questionnaire that allows cancer patients to identify and quantify the severity
      of their "concerns" and "wellbeing," as opposed to using a predetermined list.
      MYCaW administration is brief and aids in prioritizing treatment approaches. Our
      goal was to assess the convergent validity and responsiveness of MYCaW scores
      over time, the generalizability of the existing qualitative coding framework in
      different complementary and integrative oncology settings and content validity.
      METHODS: Baseline and 6-week follow-up data (n = 82) from MYCaW and FACIT-SpEx
      questionnaires were collected for a service evaluation of the Living Well with
      the Impact of Cancer course at Penny Brohn Cance Care. MYCaW convergent validity
      was determined using Spearman's rank correlation test, and responsiveness indices
      assessed score changes over time. The existing qualitative coding framework was
      reviewed using a new data set (n = 158) and coverage of concern categories
      compared with items of existing outcome measures. RESULTS: Good correlation
      between MYCaW and FACIT-SpEx score changes were achieved (r = -0.57, P >= .01).
      MYCaW Profile and Concern scores were highly responsive to change: standardized
      response mean = 1.02 and 1.08; effect size = 1.26 and 1.22. MYCaW change scores
      showed the anticipated gradient of change according to clinically relevant
      degrees of change. Categories, including "spirituality," "weight change," and
      "practical concerns" were added to the coding framework to improve
      generalizability. CONCLUSIONS: MYCaW scores were highly responsive to change,
      allowing personalized patient outcomes to be quantified; the qualitative coding
      framework appears generalizable across different integrative oncology settings
      and has broader coverage of patient-identified concerns compared with existing
      cancer-related patient-reported outcome measures.

PMID- 25384698
TI  - The role of fibrinogen as a predictor in preoperative chemoradiation for rectal
      cancer.
AB  - BACKGROUND: To perform chemoradiotherapy (CRT) effectively, it is clinically
      beneficial to identify predictors of tumor response after CRT. This study
      examined the association between plasma fibrinogen level before preoperative CRT
      and tumor response in advanced rectal cancer. METHODS: This was a retrospective
      study of 947 patients who received preoperative CRT followed by curative surgery
      for primary rectal cancer. We analyzed clinical factors that could be associated
      with pathologic tumor response in terms of downstaging (ypStage 0-I), primary
      tumor regression (ypT0-1), and complete response (ypT0N0). RESULTS: Downstaging
      was observed in 366 patients (38.6%), primary tumor regression in 187 patients
      (19.7%) and complete response in 138 patients (14.6%). Multivariate analysis
      found that pre-CRT carcinoembryonic antigen (CEA) level, fibrinogen level,
      hemoglobin level, clinical T and N classification, distance from anal verge, and
      histologic grade were significant predictive factors for downstaging; CEA level,
      fibrinogen level, and N classification predicted primary tumor regression; CEA
      level, and fibrinogen level were predictive for complete response. CONCLUSIONS:
      This study demonstrated that fibrinogen level was a significant predictor of
      pathologic tumor response after preoperative CRT.

PMID- 25384699
TI  - Morbidity among long-term survivors after pancreatoduodenectomy for pancreatic
      adenocarcinoma.
AB  - BACKGROUND: Because pancreatoduodenectomy for pancreatic adenocarcinoma is
      focused on disease-free and overall survival, morbidity among long-term survivors
      is not well described. This study sought to evaluate outcomes for long-term
      survivors of pancreatic cancer after pancreatoduodenectomy. METHODS: The authors
      identified 29 patients from their prospectively collected database of patients
      with pancreatic adenocarcinoma who had undergone pancreatoduodenectomy and were
      without evidence of disease during at least 3 years of follow-up evaluation.
      Demographics, treatment, and pathologic characteristics were collected for
      review. Data with regard to long-term sequelae also were collected, focusing on
      those complications requiring additional procedures and on the development of
      metachronous cancers. RESULTS: The median follow-up period was 83 months, with 62
      % of patients still alive. All patients received an R0 resection, and 34 % of the
      patients had N1 disease. For 42 % of the patients, no significant subsequent
      sequelae occurred. In the four remaining patients (14 %), ascites developed,
      requiring repeated paracentesis or Denver shunt, with a median time to
      development (MTD) of 63 months. Six patients (21 %) experienced a biliary
      stricture requiring stent placement (MTD, 56 months). One patient experienced
      portal venous thrombosis requiring a venous stent (MTD, 52 months), and four
      patients (14 %) experienced clinically significant ulcers (MTD, 52 months). With
      regard to metachronous cancers, two patients experienced subsequent lymphomas
      (MTD, 92 months). CONCLUSIONS: Long-term survivors among patients who undergo
      pancreatoduodenectomy for pancreatic adenocarcinoma can experience significant
      late sequelae, which often manifest more than 3 years after surgery. As such,
      continued follow-up evaluation and counseling are warranted.

PMID- 25384700
TI  - Extramammary Paget's disease in males: survival outcomes in 495 patients.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is a rare intraepithelial
      malignancy with poorly described outcomes. EMPD in men is primarily found in the
      perianal and penoscrotal areas. We assessed incidence and time trends of EMPD in
      men as well as extent and predictors of survival using the Surveillance,
      Epidemiology, and End Results (SEER) program. METHODS: The data from 18 SEER
      registries were queried for men diagnosed with EMPD from 1973 to 2009. Cases were
      categorized by primary skin location: perianal, penoscrotal, and other truncal.
      Additional data included age, race, presence of another cancer, tumor stage, and
      treatment (surgery, radiation, combination). Kaplan-Meier, univariate, and
      multivariate Cox regression analyses were conducted. RESULTS: Incidence rates of
      EMPD in men have been increasing with an annual percent change of +3.2 % (p <
      .0002) since 1978. Incidence of EMPD in blacks was nearly four times lower (p =
      .0003) and in Asians/Pacific islanders four times higher (p < .0001), relative to
      whites. Overall survival among 495 patients was 60.2 % at 120 months
      postdiagnosis. On multivariate analysis, significant factors negatively impacting
      survival were primary site in the perianal region compared to penoscrotal and
      truncal lesions (both p < .001), age older than 75 years (p < .001), and presence
      of distant versus localized disease (p = .018). Survival did not differ by race
      or presence of additional cancer. CONCLUSIONS: Survival in men with EMPD is lower
      among those with distant disease and primary tumors located in the perianal
      region. The reasons for increasing EMPD incidence over time and for the racial
      disparities in disease occurrence require further study.

PMID- 25384701
TI  - Are urologists and radiologists equally effective in determining the RENAL
      Nephrometry score?
AB  - BACKGROUND: The RENAL nephrometry score (RNS) allows description of the anatomy
      and the complexity of renal masses. This study aimed to investigate the
      interobserver reproducibility of the RNS between a radiologist and a urologist.
      METHODS: The computed tomography (CT) scans of patients undergoing partial
      nephrectomy in the authors' department between June 2010 and June 2013 were
      analyzed for determination of the RNS by a urologist and a radiologist blinded to
      the medical records. Cohen's kappa coefficient was used for interobserver
      reproducibility assessment. Correlations with per- and postoperative complication
      rates and renal function were assessed. RESULTS: The study included 52
      consecutive patients with a mean age of 55 years. The average score was 7.4 +/-
      1.7 for the urologist and 7.3 +/- 1.5 for the radiologist. The Cohen's kappa was
      0.81 for R, 0.47 for E, 0.63 for N, 0.28 for A, and 0.21 for L. The Pearson's
      coefficient for the total RNS was 0.70. The operative time and the occurrence of
      major complications were significantly correlated with the complexity assessed by
      the score of both observers. In the univariate analysis, the RNS, the American
      Society of Anesthesiologists score, and the patient's age were significantly
      associated with major complication rates. In the multivariate analysis, the RNS
      remained significantly associated with major complications. No significant
      difference in postoperative renal function according to complexity group was
      found by either the urologist or the radiologist. CONCLUSIONS: The
      reproducibility of the RNS between the radiologist and the urologist was not very
      good, especially for some items referring to the location of the tumor, although
      the major complication rates were significantly associated with the RNS for both
      observers.

PMID- 25384702
TI  - Melanoma of the vulva and vagina: principles of staging and their relevance to
      management based on a clinicopathologic analysis of 85 cases.
AB  - BACKGROUND: Primary melanomas of the vulva and vagina are rare. As a result, it
      has been difficult to develop evidence-based guidelines for their management. By
      analyzing a large series of patients with vulval and vaginal melanomas, this
      study sought to document the most common presenting features, identify clinical
      and pathologic predictors of outcome, and provide management guidelines. METHODS:
      A clinicopathologic analysis of 85 patients with primary melanomas of the vulva
      or vagina diagnosed and treated at Melanoma Institute Australia and associated
      units in Sydney, Australia, between 1960 and 2011 was performed. Predictors of
      disease-free and melanoma-specific survival (MSS) were determined. RESULTS:
      Patients with American Joint Committee on Cancer (AJCC) stage 0-II had a
      significantly better MSS (5Y MSS = 63.6 %, n = 59) compared with those with stage
      III disease (5Y MSS = 0 %, n = 12, p < 0.001). Tumor thickness, ulceration
      status, and pathologic clearance margin were significant predictors of MSS.
      Disease-free survival was predicted by these factors and additionally by tumor
      mitotic rate. CONCLUSIONS: The results of this study provide evidence to support
      the appropriateness of utilizing the AJCC (7th edition) cutaneous melanoma
      staging system for vulval and vaginal melanomas. Detection and removal of these
      melanomas at an early stage with pathologically confirmed clear margins confers
      the best chance of cure.

PMID- 25384703
TI  - An Internet-Based Collaborative Cancer Conference for Rectal Cancer Influenced
      Surgeon Treatment Recommendations.
AB  - INTRODUCTION: In many jurisdictions geographic and resource constraints are
      barriers to multidisciplinary cancer conference review of all patients undergoing
      cancer surgery. We piloted an internet-based collaborative cancer conference (I
      CCC) for rectal cancer to overcome these barriers in the LHIN4 region of Ontario
      (population 1.4 million). METHODS: Surgeons practicing at one of 10 LHIN4
      hospitals were invited to participate in I-CCC reviews. A secure internet audio
      and visual link facilitated review of cross-sectional images and case details.
      Before review, referring surgeons detailed initial treatment plans. Main
      treatment options included preoperative radiation, straight to surgery, and plan
      uncertain. Changes were noted following I-CCC review from initial to final
      treatment plan. Major changes included: redirect patient to preoperative
      radiation from straight to surgery or plan uncertain; and redirect patient to
      straight to surgery from preoperative radiation or plan uncertain. Minor changes
      included: change type of neoadjuvant therapy; request additional tests (e.g.,
      pelvic MRI); or formal MCC review. RESULTS: From November 2010 to May 2012, 20
      surgeons (7 academic and 13 community) submitted 57 rectal cancer cases for I-CCC
      review. After I-CCC review, 30 of 57 (53 %) cases had treatment plan changes: 17
      major and 13 minor. No patient or tumour factors predicted for treatment plan
      change. CONCLUSIONS: An I-CCC for rectal cancer in a large geographic region was
      feasible and influenced surgeon treatment recommendations in 53 % of cases.
      Because no factor predicted for treatment plan change, it is likely prudent that
      all rectal cancer patients undergo some form of collaborative review.

PMID- 25384704
TI  - A Cancer Reprogramming Method Using MicroRNAs as a Novel Therapeutic Approach
      against Colon Cancer: Research for Reprogramming of Cancer Cells by MicroRNAs.
AB  - BACKGROUND: We previously generated induced pluripotent stem cells by
      reprograming adipose stem cells through the introduction of microRNAs targeting
      four transcription factors (Oct3/4, Sox2, c-Myc, and Klf4). In this study, we
      aimed to reprogram cancer cells using microRNAs to explore their therapeutic
      potential. METHODS: Mature microRNAs (mir-302a-d, 369-3p and 5p, and mir-200c, as
      needed) were introduced into colon cancer cells (DLD-1, RKO, and HCT116) using
      lipofection. RESULTS: The transfected cells exhibited an embryonic stem cell-like
      morphology and expressed the undifferentiated marker genes Nanog, Oct3/4, SOX2,
      and Klf4, as well as tumor-related antigen-1-60. These cells expressed neurogenic
      or adipogenic markers, indicating that reprogramming of the cancer cells was
      partially successful. Moreover, we found that miRNA-expressing DLD-1 cells showed
      low proliferative activity in vitro and in vivo, accompanied by increased
      expression of the tumor suppressor genes p16 (ink4a) and p21 (waf1) . miRNA
      expressing DLD-1 cells also exhibited enhanced sensitivity to 5-fluorouracil,
      possibly through the downregulation of multidrug-resistant protein 8. The
      reprogrammed cells from DLD-1, RKO, and HCT116 cells exhibited reduced c-Myc
      expression, in contrast to the high c-Myc expression in the induced pluripotent
      cancer cells that were generated using four transcription factors. CONCLUSIONS:
      Our cancer reprogramming method employing simple lipofection of mature microRNAs
      is safe and well suited for clinical application, because it avoids integration
      of exogenous genes into the host genome and allows escape from augmentation of c
      Myc gene expression.

PMID- 25384705
TI  - Reirradiation Using Carbon Ions in Patients with Locally Recurrent Rectal Cancer
      at HIT: First Results.
AB  - BACKGROUND: Locally recurrent rectal cancer remains a dreaded event because
      curative resection is unlikely to be performed in a large number of cases. Carbon
      ion radiotherapy offers physical and biologic advantages. A high precise local
      dose deposition and sparing of normal tissue is possible. This work summarizes
      our experience on feasibility and early toxicity of carbon ion radiotherapy in
      previously irradiated and operated patients. METHODS: Between 2010 and 2013, a
      total of 19 patients with a median age of 62 years (range 14-76 years) received
      carbon ion irradiation to treat locally recurrent rectal cancer at the Heidelberg
      Ion Beam Therapy Center (HIT). All patients had a history of surgery and pelvic
      radiotherapy of at least 50.4 Gy. Median dose was 36 Gy [relative biologic
      efficacy (RBE)] [range 36-51 Gy(RBE)], and median planning target volume was 456
      ml (range 75-1,597 ml). Some patients were treated in the recruiting phase I/II
      of the PANDORA study (NCT01528683). RESULTS: Median follow-up was 7.8 months.
      Four patients were diagnosed with local relapse after carbon ion radiotherapy,
      and three patients developed distant metastases. Estimated mean local progression
      free survival was 20.6 months by the Kaplan-Meier estimator. Two patients had
      preexisting rectovaginal fistula, and another patient had a preexisting presacral
      localized abscess formation in which the local relapse took place. No grade III
      or higher toxicities were observed. CONCLUSIONS: Our first experiences in a
      pretreated patient group with a dismal prognosis are encouraging, and therapy
      related side effects are mild. Longer follow-up is required to determine possible
      late effects and long-term disease control.

PMID- 25384706
TI  - Single-incision multiport laparoendoscopic surgery using a short-type flexible
      endoscope and its usefulness in cholecystectomy.
AB  - INTRODUCTION: We previously demonstrated the advantages of a short-type flexible
      endoscope as a working scope in laparoscopic surgery through single-incision
      procedures in animal experiments. In this report, we examined the outcomes of
      laparoscopic surgery through a single incision using a flexible endoscope in a
      clinical setting. Specifically, we performed cholecystectomy using single
      incision multiport laparoendoscopic (SIMPLE) surgery. METHODS: Thirteen patients
      with cholecystolithiasis or gallbladder polyp underwent SIMPLE cholecystectomy
      using a newly developed short-type flexible endoscope with a working length of 60
      cm. Twenty-seven patients underwent standard single-incision laparoscopic
      cholecystectomy using a 5-mm rigid laparoscope. We retrospectively compared the
      surgical outcomes between the two groups. RESULTS: SIMPLE cholecystectomy using
      the short-type flexible endoscope was successfully carried out. No gallbladder
      perforation occurred, but perforation occurred in four cases in the standard
      laparoscopic cholecystectomy group; however, the difference was not statistically
      significant. Although no other surgical outcomes differed between the two groups,
      the flexible endoscope had several advantages over the standard laparoscope. The
      scope provided a flexible view of the operating field. The gallbladder dissection
      using the cutting device via the scope was easier and safer than that in standard
      single-incision laparoscopic cholecystectomy. The water-jet, suctioning, and self
      cleaning lens functions of the scope served the surgery well. CONCLUSIONS: SIMPLE
      cholecystectomy using a short-type flexible endoscope has surgical outcomes
      equivalent to those of standard single-incision laparoscopic cholecystectomy, but
      this endoscope with multiple functions may make the surgical procedures less
      stressful and safer.

PMID- 25384707
TI  - Unfolded protein response in filamentous fungi-implications in biotechnology.
AB  - The unfolded protein response (UPR) represents a mechanism to preserve
      endoplasmic reticulum (ER) homeostasis that is conserved in eukaryotes. ER stress
      caused by the accumulation of potentially toxic un- or misfolded proteins in the
      ER triggers UPR activation and the induction of genes important for protein
      folding in the ER, ER expansion, and transport from and to the ER. Along with
      this adaptation, the overall capacity for protein secretion is markedly increased
      by the UPR. In filamentous fungi, various approaches to employ the UPR for
      improved production of homologous and heterologous proteins have been
      investigated. As the effects on protein production were strongly dependent on the
      expressed protein, generally applicable strategies have to be developed. A
      combination of transcriptomic approaches monitoring secretion stress and basic
      research on the UPR mechanism provided novel and important insight into the
      complex regulatory cross-connections between UPR signalling, cellular physiology,
      and developmental processes. It will be discussed how this increasing knowledge
      on the UPR might stimulate the development of novel strategies for using the UPR
      as a tool in biotechnology. 

PMID- 25384709
TI  - Competency and an active learning program in undergraduate nursing education.
AB  - AIMS: To evaluate the effect of an active learning program on competency of
      senior students. BACKGROUND: Active learning strategies have been used to help
      students achieve desired nursing competency, but their effectiveness has not been
      systematically examined. DESIGN: A descriptive, cross-sectional comparative
      design was used. Two cohort group comparisons using t-test were made: one in an
      active learning group and the other in a traditional learning group. METHODS: A
      total of 147 senior nursing students near graduation participated in this study:
      73 in 2010 and 74 in 2013. The active learning program incorporated high-fidelity
      simulation, situation-based case studies, standardized patients, audio-video
      playback, reflective activities and technology such as a SmartPad-based program.
      RESULTS: The overall scores of the nursing competency in the active group were
      significantly higher than those in the traditional group. Of five overall
      subdomains, the scores of the special and general clinical performance
      competency, critical thinking and human understanding were significantly higher
      in the active group than in the traditional group. Importance-performance
      analysis showed that all five subdomains of the active group clustered in the
      high importance and high performance quadrant, indicating significantly better
      achievements. In contrast, the students in the traditional group showed scattered
      patterns in three quadrants, excluding the low importance and low performance
      quadrants. This pattern indicates that the traditional learning method did not
      yield the high performance in most important areas. CONCLUSION: The findings of
      this study suggest that an active learning strategy is useful for helping
      undergraduate students to gain competency.

PMID- 25384711
TI  - Risk management for moisture related effects in dry manufacturing processes: a
      statistical approach.
AB  - A risk- and science-based approach to control the quality in pharmaceutical
      manufacturing includes a full understanding of how product attributes and process
      parameters relate to product performance through a proactive approach in
      formulation and process development. For dry manufacturing, where moisture
      content is not directly manipulated within the process, the variability in
      moisture of the incoming raw materials can impact both the processability and
      drug product quality attributes. A statistical approach is developed using
      individual raw material historical lots as a basis for the calculation of
      tolerance intervals for drug product moisture content so that risks associated
      with excursions in moisture content can be mitigated. The proposed method is
      based on a model-independent approach that uses available data to estimate
      parameters of interest that describe the population of blend moisture content
      values and which do not require knowledge of the individual blend moisture
      content values. Another advantage of the proposed tolerance intervals is that, it
      does not require the use of tabulated values for tolerance factors. This
      facilitates the implementation on any spreadsheet program like Microsoft Excel. A
      computational example is used to demonstrate the proposed method. 

PMID- 25384710
TI  - The Etiology of Juvenile Idiopathic Arthritis.
AB  - Over the years, the commonly used term to describe juvenile idiopathic arthritis
      (JIA) has changed. By definition, JIA includes all types of arthritis with no
      apparent cause, lasting more than 6 weeks, in patients aged less than 16 years at
      onset. JIA pathogenesis is still poorly understood: the interaction between
      environmental factors and multiple genes has been proposed as the most relevant
      working mechanism to the development of JIA. The concept that various microbes
      that colonize or infect not only the mucosal surfaces, like the oral cavity, but
      also the airways and gut might trigger autoimmune processes, resulting in chronic
      arthritides, and JIA was first drafted at the outset of last century. JIA
      development might be initiated and sustained by the exposure to environmental
      factors, including infectious agents which affect people at a young age,
      depending on the underlying genetic predisposition to synovial inflammation. Many
      data from patients with JIA suggest a scenario in which different external
      antigens incite multiple antigen-specific pathways, cytotoxic T cell responses,
      activation of classical complement cascade, and production of proinflammatory
      cytokines. In this review, emphasis is paid not only to the potential role of
      parvovirus B19 and Epstein-Barr virus in primis but also to the general
      involvement of different bacteria as Salmonella spp., Shigella spp.,
      Campylobacter spp., Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bartonella
      henselae, and Streptococcus pyogenes for the development of immune-mediated
      arthritides during childhood. No unequivocal evidence favoring or refuting these
      associations has been clearly proved, and today, the strict definition of JIA
      etiology remains unknown. The infection can represent a random event in a
      susceptible individual, or it can be a necessary factor in JIA development,
      always in combination with a peculiar genetic background. Further studies are
      needed in order to address the unsolved questions concerning this issue.

PMID- 25384712
TI  - Advancing the electrochemistry of the hydrogen-evolution reaction through
      combining experiment and theory.
AB  - The electrocatalytic hydrogen-evolution reaction (HER), as the main step of water
      splitting and the cornerstone of exploring the mechanism of other multi-electron
      transfer electrochemical processes, is the subject of extensive studies. A large
      number of high-performance electrocatalysts have been developed for HER
      accompanied by recent significant advances in exploring its electrochemical
      nature. Herein we present a critical appraisal of both theoretical and
      experimental studies of HER electrocatalysts with special emphasis on the
      electronic structure, surface (electro)chemistry, and molecular design. It
      addresses the importance of correlating theoretical calculations and
      electrochemical measurements toward better understanding of HER electrocatalysis
      at the atomic level. Fundamental concepts in the computational quantum chemistry
      and its relation to experimental electrochemistry are also presented along with
      some featured examples. 

PMID- 25384715
TI  - Everything I know about sex I wish I learned from a ciliate.

PMID- 25384713
TI  - Efficacy of combined anti-TNF-alpha and surgical therapy in perianal and
      enterocutaneous fistulizing Crohn's disease--clinical observations from a
      tertiary Eastern European center.
AB  - BACKGROUND AND AIMS: Recently, anti-TNF-alpha therapy has increasingly been used
      in the treatment of perianal Crohn's disease (PCD), but there is only limited
      data regarding its short- and long-term efficacy. MATERIAL AND METHODS: The
      medical records of 68 patients treated with anti-TNF-alpha for PCD were assessed
      retrospectively. Rate of complex fistulas was 75%. Every patient received
      induction therapy, but in 20 cases the treatment was discontinued before week 52
      due to funding regulations, an allergic reaction, or compliance problems. On week
      12, the luminal activity decreased in more than 80% of the cases and the complete
      remission (CR) rate was about 60%; by the end of the first year, this ratio did
      not change substantially. Complete fistula closure was achieved in 26 cases
      (38.3%) and 53 patients (51.5%) showed a partial response during the 1-year
      period. Regarding both perianal and luminal activities, CR rate was achieved in
      23 cases (33.8%). However, after the biological therapy was discontinued,
      recurrence of fistulas could be detected in every second patient. Additional
      surgical intervention was performed in 45% of patients during the 1-year period
      (seton drainage of fistulas and abscess drainage). CONCLUSION: The anti-TNF-alpha
      therapy combined with surgery is an effective treatment of PCD. Approximately
      every third patient revealed complete fistula closure, while half of the other
      cases showed a partial response. Due to the high rate of fistula recurrence after
      stopping the biological therapy, more than 1 year of anti-TNF-alpha treatment may
      be beneficial.

PMID- 25384717
TI  - Effects of elaidic acid, a predominant industrial trans fatty acid, on bacterial
      growth and cell surface hydrophobicity of lactobacilli.
AB  - The consumption of trans fatty acids (TFAs) increases the risk of cardiovascular
      diseases and coronary heart disease in human, and there are no effective ways to
      remove TFAs after consumption. The aim of this study was to investigate the
      effects of elaidic acid on bacterial growth, cell surface hydrophobicity of
      lactobacilli, and metabolism of elaidic acid by lactobacilli. Lactobacilli were
      inoculated in MRS broth containing 0, 100, 200, and 500 mg/L of elaidic acid.
      Viable cell counts of lactobacilli were enumerated, concentrations of elaidic
      acid were determined, and cell surface hydrophobicity of lactobacilli was
      measured. The results showed that the growth of lactobacilli was significantly
      inhibited by 500 mg/L of elaidic acid, however, a cell count of 8.50 log10 CFU/mL
      was still reached for tested lactobacilli after 24-h incubation. In particular, a
      reduction of elaidic acid was found for tested lactobacilli after 24-h incubation
      as compared to its initial concentration of 200 mg/L. However, cell surface
      hydrophobicity showed no correlations with the metabolism of elaidic acid by
      lactobacilli. Moreover, elaidic acid was able to influence cell surface
      hydrophobicity, and the decrease in hydrophobicity was more obvious in
      Lactobacillus paracasei and Lactobacillus casei compared with that in other
      tested lactobacilli. This study suggests that elaidic acid could change
      physiochemical surface properties of lactobacilli and the lactobacilli have the
      potential to reduce TFAs. 

PMID- 25384718
TI  - Application of Pseudomonas flava WD-3 for sewage treatment in constructed wetland
      in winter.
AB  - Recently, constructed wetland was applied for sewage treatment globally due to
      its high efficiency and relatively low investment. However, operation of many
      constructed wetlands in cold winter is quite difficult due to the inhibition
      effect of low temperature. The objective of this experiment is to study the
      sewage treatment efficiency of Pseudomonas flava WD-3 in the integrated vertical
      flow constructed wetland (IVCW) during winter with different dosages (bacterial
      suspension concentration: 4.575*10(8 )mL(-1)). Two treatments were designed,
      inoculation of P. flava WD-3 with different dosages and the control without
      bacterium incubation. A simplified Monod model was applied to simulate and
      evaluate the pollutant removal efficiency of this bacterial strain with respect
      to its dosages. Results indicated that P. flava WD-3 could degrade organic
      pollutants, nitrogen, and phosphorus nutrients from wastewater effectively. The
      optimal dosage of this strain was 6.0%, and the removal rates of chemical oxygen
      demand (COD), ammonium nitrogen (NH4+-N), and total phosphorous (TP) were 85.82
      87.00%, 73.91-84.18%, and 82.04-87.00%, respectively. Furthermore, the average
      removal efficiencies of COD, NH4+-N, and TP were 1.46, 1.49, and 1.76 times,
      respectively, than the control. The simplified Monod model accurately predicted
      the pollutant removal efficiency of P. flava WD-3 in the IVCW system in winter.

PMID- 25384719
TI  - Dual analysis of host and pathogen transcriptomes in ostreid herpesvirus 1
      positive Crassostrea gigas.
AB  - Ostreid herpesvirus type 1 (OsHV-1) has become a problematic infective agent for
      the Pacific oyster Crassostrea gigas. In particular, the OsHV-1 MUVar subtype has
      been associated with severe mortality episodes in oyster spat and juvenile
      oysters in France and other regions of the world. Factors enhancing the
      infectivity of the virus and its interactions with susceptible and resistant
      bivalve hosts are still to be understood, and only few studies have explored the
      expression of oyster or viral genes during productive infections. In this work,
      we have performed a dual RNA sequencing analysis on an oyster sample with a high
      viral load. High sequence coverage allowed us to thoroughly explore the OsHV-1
      transcriptome and identify the activated molecular pathways in C. gigas. The
      identification of several highly induced and defence-related oyster transcripts
      supports the crucial role played by the innate immune system against the virus
      and opportunistic microbes possibly contributing to subsequent spat mortality. 

PMID- 25384720
TI  - Comparing Diagnostic Outcomes of Autism Spectrum Disorder Using DSM-IV-TR and DSM
      5 Criteria.
AB  - Controversy exists regarding the DSM-5 criteria for ASD. This study tested the
      psychometric properties of the DSM-5 model and determined how well it performed
      across different gender, IQ, and DSM-IV-TR sub-type, using clinically collected
      data on 227 subjects (median age = 3.95 years, majority had IQ > 70). DSM-5 was
      psychometrically superior to the DSM-IV-TR model (Comparative Fit Index of 0.970
      vs 0.879, respectively). Measurement invariance revealed good model fit across
      gender and IQ. Younger children tended to meet fewer diagnostic criteria. Those
      with autistic disorder were more likely to meet social communication and
      repetitive behaviors criteria (p < .001) than those with PDD-NOS. DSM-5 is a
      robust model but will identify a different, albeit overlapping population of
      individuals compared to DSM-IV-TR.

PMID- 25384721
TI  - Prospects for better nutrition in India.
AB  - Being home to 31% of the world's children who are stunted and 42% of those who
      are underweight, and with many children and adults affected by micronutrient
      deficiencies, India is facing huge challenges in the field of nutrition. Even
      though the Indian Government is investing vast amounts of money into programs
      that aim to enhance food security, health and nutrition (the Integrated Child
      Development Services program alone costs 3 billion USD per year), overall impact
      has been rather disappointing. However, there are some bright spots on the
      horizon. The recent District Level Health Surveys (DLHS-4) do show significant
      progress, ie a reduction in stunting of around 15% over the past 6 years in a few
      states for which preliminary results are available. The reasons for this
      reduction are not unambiguous and appear to include state government commitment,
      focus on the 'window of opportunity', improved status and education of women, a
      lowered fertility rate, and combinations of nutrition- specific and nutrition
      sensitive interventions. Apart from the government many other agencies play a
      role in driving improvements in nutrition. Since 2006 the Global Alliance for
      Improved Nutrition (GAIN) has worked with a range of partners to improve access
      to nutritious foods for large parts of the population, through public and private
      delivery channels. This supplement presents a selection of these activities,
      ranging from a capacityassessment of frontline workers in the ICDS system, large
      scale staple food fortification, salt iodization, fortification of mid-day meals
      for school children and decentralized complementary food production. 

PMID- 25384722
TI  - Improving the nutrition quality of the school feeding program (Mid day meal) in
      India through fortification: a case study.
AB  - Micronutrient malnutrition is widely prevalent in school children in India.
      India's national school feeding program, the Mid-Day Meal (MDM) scheme, is the
      largest in the world and caters to 120 million children in primary schools.
      Complementary strategies such as deworming or fortifying meals provided through
      the MDM scheme could increase the nutritional impact of this program. India's
      Supreme Court has directed that only hot, cooked meals be provided in MDM,
      through a decentralised model. However, in urban areas, big centralised kitchens
      cook and serve a large number of schools, with some kitchens serving up to
      150,000 children daily. The objective of this project was to test the operational
      feasibility of fortifying the school meal in centralised kitchens, as well as the
      acceptability of fortified meals by recipients. A pilot was conducted in 19
      central kitchens run by the Naandi Foundation in four different States. Several
      food vehicles were used for fortification: wheat flour, soyadal- analogue and
      biscuits. More than 750, 000 children were reached with fortified food on all
      school days for a period of one year. Fortified food was found to be acceptable
      to all stakeholders. The government is in favour of continuing fortification. The
      Naandi Foundation has adopted fortification as their norm and continues to
      fortify all meals provided from their central kitchens. IN CONCLUSION:
      fortification of school meals with micronutrients can be integrated in the normal
      cooking process and is well accepted by all stakeholders. This pilot could hold
      lessons for other states in adopting fortification in MDM.

PMID- 25384723
TI  - Production of fortified food for a public supplementary nutrition program:
      performance and viability of a decentralised production model for the Integrated
      Child Development Services Program, India.
AB  - Integrated Child Development Services in India through its supplementary
      nutrition programme covers over 100 million children, pregnant and lactating
      women across the country. Providing a hot cooked meal each day to children aged
      between 3-6 years and a take-home ration to children aged between 6-36 months,
      pregnant and lactating women, the Integrated Child Development Services faces a
      monumental task to deliver this component of services of desired quality and
      regularity at scale. From intermediaries or contractors who acted as agents for
      procuring and distributing food to procurement directly from large food
      manufacturers to using women groups as food producers, different State
      Governments have adopted a variety of strategies to procure and distribute food,
      especially the take-home ration. India's Supreme Court, through its directive of
      2004, encouraged the Government to engage women's groups for the production of
      the supplementary food. This study was conducted to determine the operational
      performance, economic sustainability and social impact of a decentralised
      production model for India's Supplementary Nutrition Program, in which women
      groups run smallscale industrialised units. Data were collected through
      observation, interviews and group discussions with key stakeholders. Operational
      performance was analysed through standard performance indicators that measured
      consistency in production, compliance with quality standards and distribution
      regularity. Assessment of the economic viability included cost structure
      analysis, five-year projections, and financial ratios. Social impact was assessed
      using a qualitative approach. The pilot unit has demonstrated its operational
      performance and cost-efficiency. More data is needed to evaluate the scalability
      and sustainability of this decentralised model. 

PMID- 25384724
TI  - Capacity of frontline ICDS functionaries to support caregivers on infant and
      young child feeding (IYCF) practices in Gujarat, India.
AB  - Improved infant and young child feeding practices have the potential to improve
      child growth and development outcomes in India. Anganwadi Workers, the frontline
      government functionaries of the national nutrition supplementation programme in
      India, play a vital role in promoting infant and young child feeding practices in
      the community. The present study assessed the Anganwadi Workers' knowledge of
      infant and young child feeding practices, and their ability to counsel and
      influence caregivers regarding these practices. Eighty Anganwadi Workers from
      four districts of Gujarat participated in assessment centres designed to evaluate
      a range of competencies considered necessary for the successful promotion of
      infant and young child feeding practices. The results of the evaluation showed
      the Anganwadi Workers possessing more knowledge about infant and young child
      feeding practices like initiation of breastfeeding, pre-lacteal feeding and
      colostrum, age of introduction of complementary foods, portion size and feeding
      frequency than about domains which appear to have a direct bearing on practices.
      A huge contrast existed between the Anganwadi Workers' knowledge and their
      ability to apply this in formal counselling sessions with caregivers. Inability
      to empathetically engage with caregivers, disregard for taking the feeding
      history of children, poor active listening skills and inability to provide need
      based advice were pervasive during counselling. In conclusion, to ensure enhanced
      interaction between the Anganwadi Workers and caregivers on infant and young
      child feeding practices, a paradigm shift in training is required, making
      communication processes and counselling skills central to the training. 

PMID- 25384725
TI  - The National Coalition for Sustained Optimal Iodine intake (NSOI): a case study
      of a successful experience from India.
AB  - Iodine deficiency disorders (IDD) constitute the single most important
      preventable cause of mental handicap at global level. Recognizing the importance
      of coordination and synergy of the activities of wide range of universal salt
      iodisation (USI) stakeholders, WHO/ Unicef/ ICCIDD has prescribed a national
      multi-sectoral coalition as one of the ten indicators essential for attaining
      sustainable elimination of IDD at national level. Challenge for coordination
      among different stakeholders of IDD/USI is even greater in democratic and diverse
      country like India. In the present article we present successful experience from
      India regarding formation of a national coalition and contributions made by the
      coalition towards promoting USI in India. The activities of the national
      coalition in India are classified into three phases; 1) Phase 1- year 2006 to
      2009- the inception; 2) Phase 2- year 2009 to 2012- consolidation; 3) Phase 3-
      year 2013 and ongoing- expansion. The National coalition for Sustained Optimal
      Iodine Intake (NSOI) has been instrumental in ensuring greater coordination and
      synergy amongst IDD and USI stakeholders in India and partially responsible for
      the current 71 percentage household level coverage of adequately iodised salt.
      The most significant contribution of the national coalition has been to act as a
      high level advocacy channel and provide a platform for regular dialogue for all
      partners of the coalition. With "mission" approach and allocation of optimal
      resource, India can achieve and should achieve USI by 2015, an apt culmination of
      a decade of existence of the national coalition. 

PMID- 25384726
TI  - Food fortification as a complementary strategy for the elimination of
      micronutrient deficiencies: case studies of large scale food fortification in two
      Indian States.
AB  - The burden of micronutrient malnutrition is very high in India. Food
      fortification is one of the most cost-effective and sustainable strategies to
      deliver micronutrients to large population groups. Global Alliance for Improved
      Nutrition (GAIN) is supporting large-scale, voluntary, staple food fortification
      in Rajasthan and Madhya Pradesh because of the high burden of malnutrition,
      availability of industries capable of and willing to introduce fortified staples,
      consumption patterns of target foods and a conducive and enabling environment.
      High extraction wheat flour from roller flour mills, edible soybean oil and milk
      from dairy cooperatives were chosen as the vehicles for fortification.
      Micronutrients and levels of fortification were selected based on vehicle
      characteristics and consumption levels. Industry recruitment was done after a
      careful assessment of capability and willingness. Production units were equipped
      with necessary equipment for fortification. Staffs were trained in fortification
      and quality control. Social marketing and communication activities were carried
      out as per the strategy developed. A state food fortification alliance was formed
      in Madhya Pradesh with all relevant stakeholders. Over 260,000 MT of edible oil,
      300,000 MT of wheat flour and 500,000 MT of milk are being fortified annually and
      marketed. Rajasthan is also distributing 840,000 MT of fortified wheat flour
      annually through its Public Distribution System and 1.1 million fortified Mid-day
      meals daily through the centralised kitchens. Concurrent monitoring in Rajasthan
      and Madhya has demonstrated high compliance with all quality standards in
      fortified foods. 

PMID- 25384727
TI  - Genome sequence of mungbean and insights into evolution within Vigna species.
AB  - Mungbean (Vigna radiata) is a fast-growing, warm-season legume crop that is
      primarily cultivated in developing countries of Asia. Here we construct a draft
      genome sequence of mungbean to facilitate genome research into the subgenus
      Ceratotropis, which includes several important dietary legumes in Asia, and to
      enable a better understanding of the evolution of leguminous species. Based on
      the de novo assembly of additional wild mungbean species, the divergence of what
      was eventually domesticated and the sampled wild mungbean species appears to have
      predated domestication. Moreover, the de novo assembly of a tetraploid Vigna
      species (V. reflexo-pilosa var. glabra) provides genomic evidence of a recent
      allopolyploid event. The species tree is constructed using de novo RNA-seq
      assemblies of 22 accessions of 18 Vigna species and protein sets of Glycine max.
      The present assembly of V. radiata var. radiata will facilitate genome research
      and accelerate molecular breeding of the subgenus Ceratotropis. 

PMID- 25384728
TI  - Association of polymorphisms in IL6 gene promoter region with type 1 diabetes and
      increased albumin-to-creatinine ratio.
AB  - BACKGROUND: Pro-inflammatory cytokines, such as interleukin-6 (IL-6), have been
      considered as key factors in type 1 diabetes mellitus (T1DM) and diabetic
      nephropathy, thus, our aim was to investigate the association of IL6-174G>C
      (rs1800795) and -634C>G (rs1800796) polymorphisms with T1DM susceptibility and
      diabetic nephropathy. METHODS: These polymorphisms were analyzed in 144 children
      and adolescents with T1DM and 173 normoglycemic control subjects. Glycemic
      control, laboratory parameters of kidney function and serum lipids were
      evaluated. By studying only T1DM patients, we evaluated the polymorphisms
      associated with relevant biochemical parameters in various genetic models.
      RESULTS: Type 1 diabetes mellitus patients showed poor glycemic control and
      albumin-to-creatinine ratio, total cholesterol and LDL-cholesterol levels
      increased when compared with normoglycemic subjects (p < 0.001, p = 0.004 and p <
      0.001, respectively). IL6-174C allele was associated with an increased risk of
      developing T1DM (OR = 1.53, CI = 1.01-2.31, p = 0.044). In the T1DM group, IL6
      174CC carriers showed higher concentrations of glycated hemoglobin (p = 0.029),
      albumin-to-creatinine ratio (p = 0.021), total cholesterol (p = 0.010), and LDL
      cholesterol (p = 0.002), when compared with GG+GC carriers. No association was
      found for the IL6-634C>G polymorphism. CONCLUSIONS: These results suggest that
      IL6-174G>C may contribute to T1DM and increased albumin-to-creatinine ratio as
      well as to poor glycemic control and hyperlipidemia.

PMID- 25384729
TI  - Human liver stem cells and derived extracellular vesicles improve recovery in a
      murine model of acute kidney injury.
AB  - INTRODUCTION: Several cellular sources of stem cells have been tested in the
      attempt to yield innovative interventions in acute kidney injury (AKI). Human
      liver stem cells (HLSCs) are cells isolated from the normal adult human liver
      which are gaining attention for their therapeutic potential. In the present
      study, we investigated whether HLSCs and the derived extracellular vesicles may
      promote tubular regeneration after AKI induced by glycerol injection in severe
      combined immune-deficient mice. METHODS: HLSCs were expanded and conditioned
      medium (CM) and extracellular vesicles (EVs) were purified. HLSCs and their
      bioproducts were tested in a model of AKI induced by intra-muscle glycerol
      injection. Renal function and morphology were evaluated five days after induction
      of damage. The effect of EVs on proliferation and apoptosis of murine renal
      tubular cells was tested in vitro. RESULTS: We found that intravenous injection
      of 3.5*105 HLSCs into mice three days after induction of AKI significantly
      improved functional and morphological recovery. The injection of HLSCs decreased
      creatinine and urea, as well as hyaline cast formation, tubular necrosis and
      enhanced in vivo tubular cell proliferation. The effect of soluble factors
      release by HLSCs in the regenerative processes was also studied. CM produced by
      HLSCs, mimicked the effect of the cells. However, depletion of EVs significantly
      reduced the functional and morphological recovery of CM. Moreover, we found that
      purified HLSC-derived EVs ameliorated renal function and morphology in a manner
      comparable to the cells. In vitro HLSC-derived EVs were shown to stimulate
      proliferation and inhibit apoptosis of murine renal tubular cells. CONCLUSIONS:
      These results indicate that HLSCs increase recovery after AKI. EVs are the main
      component of HLSC-derived CM capable of promoting regeneration in experimental
      AKI.

PMID- 25384730
TI  - Detection and discrimination of four Aspergillus section Nigri species by PCR.
AB  - Species of Aspergillus section Nigri are not easily distinguished by traditional
      morphological techniques, and typically are identified by DNA sequencing methods.
      We developed four PCR primers to distinguish between Aspergillus niger,
      Aspergillus welwitschiae, Aspergillus carbonarius and Aspergillus tubingensis,
      based on species-conserved differences in the calmodulin gene sequence. PCR
      amplification from total DNA using these primers was species specific; no
      amplification occurred from nontarget species DNA for each primer pair. Species
      specific PCR could distinguish between species in mixed DNA templates, indicating
      a utility in determining culture uniformity of isolated Aspergillus strains. In
      addition, with these primer sets, each species could be detected in soil
      following mixed-species inoculation with Aspergillus spores. This indicates that
      PCR with these species-specific primers may be useful in determining the
      distribution of Aspergillus species in environmental samples without the need for
      species identification from isolated strains, as well as detecting species that
      may be infrequently isolated by culture-based methods.

PMID- 25384731
TI  - Covalent dimers of 1,3-diphenylisobenzofuran for singlet fission: synthesis and
      electrochemistry.
AB  - The synthesis of covalent dimers in which two 1,3-diphenylisobenzofuran units are
      connected through one phenyl substituent on each is reported. In three of the
      dimers, the subunits are linked directly, and in three others, they are linked
      via an alkane chain. A seventh new compound in which two 1,3
      diphenylisobenzofuran units share a phenyl substituent is also described. These
      materials are needed for investigations of the singlet fission process, which
      promises to increase the efficiency of solar cells. The electrochemical oxidation
      and reduction of the monomer, two previously known dimers, and the seven new
      compounds have been examined, and reversible redox potentials have been compared
      with results obtained from density functional theory. Although the overall
      agreement is satisfactory, some discrepancies are noted and discussed. 

PMID- 25384732
TI  - Occupational exposures and longitudinal lung function decline.
AB  - BACKGROUND: Few longitudinal studies have been conducted on occupational exposure
      and lung function. This study investigated occupational dust exposure effects on
      lung function and whether genetic variants influence such effects. METHODS: The
      study population (1,332 participants) was from the Framingham Heart Study, in
      which participant lung function measures were available from up to five
      examinations over nearly 17 years. Occupational dust exposures were classified
      into "more" and "less" likely dust exposure. We used linear mixed effects models
      for the analysis. RESULTS: Participants with more likely dust exposure had a mean
      4.5 mL/year excess loss rate of FEV1 over time. However, occupational dust
      exposures alone or interactions with age or time had no significant effect on
      FEV1 /FVC. No statistically significant effects of genetic modifications in the
      different subgroups were identified for FEV1 loss. CONCLUSIONS: Occupational dust
      exposures may accelerate the rate of FEV1 loss but not FEV1 /FVC loss.

PMID- 25384734
TI  - Effects of N-acetylcysteine on substance use in bipolar disorder: A randomised
      placebo-controlled clinical trial.
AB  - OBJECTIVE: To evaluate the effect of N-acetylcysteine (NAC) on substance use in a
      double-blind, placebo-controlled trial of NAC in bipolar disorder. It is
      hypothesised that NAC will be superior to placebo for reducing scores on the
      Clinical Global Impressions scale for Substance Use (CGI-SU). METHODS:
      Participants were randomised to a 6-months of treatment with 2 g/day NAC (n = 38)
      or placebo (n = 37). Substance use was assessed at baseline using a Habits
      instrument. Change in substance use was assessed at regular study visits using
      the CGI-SU. RESULTS: Among the 75 participants 78.7% drank alcohol (any
      frequency), 45.3% smoked tobacco and 92% consumed caffeine. Other substances were
      used by fewer than six participants. Caffeine use was significantly lower for NAC
      treated participants compared to placebo at week 2 of treatment but not at other
      study visits. CONCLUSIONS: NAC appeared to have little effect on the participants
      who were using substances. A larger study on a substance-using population will be
      necessary to determine if NAC may be a useful treatment for substance use.

PMID- 25384733
TI  - The expansion of GPCR transactivation-dependent signalling to include
      serine/threonine kinase receptors represents a new cell signalling frontier.
AB  - G protein-coupled receptor (GPCR) signalling is mediated through transactivation
      independent signalling pathways or the transactivation of protein tyrosine kinase
      receptors and the recently reported activation of the serine/threonine kinase
      receptors, most notably the transforming growth factor-beta receptor family.
      Since the original observation of GPCR transactivation of protein tyrosine kinase
      receptors, there has been considerable work on the mechanism of transactivation
      and several pathways are prominent. These pathways include the "triple membrane
      bypass" pathway and the generation of reactive oxygen species. The recent
      recognition of GPCR transactivation of serine/threonine kinase receptors
      enormously broadens the GPCR signalling paradigm. It may be predicted that the
      transactivation of serine/threonine kinase receptors would have mechanistic
      similarities with transactivation of tyrosine kinase pathways; however, initial
      studies suggest that these two transactivation pathways are mechanistically
      distinct. Important questions are the relative importance of tyrosine and
      serine/threonine transactivation pathways, the contribution of transactivation to
      overall GPCR signalling, mechanisms of transactivation and the range of cell
      types in which this phenomenon occurs. The ultimate significance of
      transactivation-dependent signalling remains to be defined but it appears to be
      prominent and if so will represent a new cell signalling frontier. 

PMID- 25384735
TI  - Exploring the role of face processing in facial emotion recognition in
      schizophrenia.
AB  - OBJECTIVE: Impairment in emotion perception represents a fundamental feature of
      schizophrenia with important consequences in social functioning. A fundamental
      unresolved issue is the relationship between emotion perception and face
      perception. The aim of the present study was to examine whether facial identity
      recognition (Identity Discrimination) is a factor predicting facial emotion
      recognition in the context of the other factors, known as contributing to emotion
      perception, such as cognitive functions and symptoms. METHODS: We enrolled 58
      stable schizophrenic out-patients and 47 healthy subjects. Facial identity
      recognition and emotion perception were assessed with the Comprehensive Affect
      Testing System. Different multiple regression models with backward elimination
      were performed in order to discover the relation of each significant variable
      with emotion perception. RESULTS: In a regression including the six significant
      variables (age, positive symptomatology, Identity Discrimination, attentive
      functions, verbal memory-learning, executive functions) versus emotion
      processing, only attentive functions (standardised beta = 0.264, p = 0.038) and
      Identity Discrimination (standardised beta = 0.279, p = 0.029) reached a
      significant level. Two partial regressions were performed including five
      variables, one excluding attentive functions and the other excluding Identity
      Discrimination. When we excluded attentive functions, the only significant
      variable was Identity Discrimination (standardised beta = 0.278, p = 0.032). When
      we excluded Identity Discrimination, both verbal memory-learning (standardised
      beta = 0.261, p = 0.042) and executive functions (standardised beta = 0.253, p =
      0.048) were significant. CONCLUSIONS: Our results emphasised the role of face
      perception and attentional abilities on affect perception in schizophrenia. We
      additionally found a role of verbal memory-learning and executive functions on
      emotion perception. The relationship between those above-mentioned variables and
      emotion processing could have implications for cognitive rehabilitation.

PMID- 25384736
TI  - Progressive brain changes in schizophrenia: a 1-year follow-up study of diffusion
      tensor imaging.
AB  - OBJECTIVE: Recent cross-sectional studies suggest that brain changes in
      schizophrenia are progressive during the course of the disorder. However, it
      remains unknown whether this is a global process or whether some brain areas are
      affected to a greater degree. The aim of this study was to examine the
      longitudinal brain changes in patients with chronic older schizophrenia by
      magnetic resonance imaging (MRI). METHODS: Three-dimensional (3D) T1-weighted and
      diffusion tensor (DT) MRI were performed twice on each of 16 chronic older
      schizophrenia patients (mean age = 58.1 +/- 6.7 years ) with an interval of 1
      year between imaging sessions. To clarify the longitudinal morphological and
      white matter changes, volume data and normalised diffusion tensor imaging (DTI)
      metrics were compared between the first and follow-up studies using a paired t
      test. RESULTS: Focal cortical volume loss was observed in the left prefrontal
      lobe and anterior cingulate on volumetric study. In addition, DTI metrics changed
      significantly at the bilateral posterior superior temporal lobes, left insula,
      genu of the corpus callosum and anterior cingulate. CONCLUSION: There are ongoing
      changes in the brains of schizophrenic patients during the course of the illness.
      Discrepancies between volume data and DTI metrics may indicate that the pattern
      of progressive brain changes varies according to brain region.

PMID- 25384737
TI  - Biological sample collection for clinical proteomics: existing SOPs.
AB  - Proteomic study of clinical samples aims at the better understanding of
      physiological and pathological conditions, as well as the discovery of diagnostic
      and prognostic markers for the latter. Quantitative and/or qualitative variations
      of body fluid proteome may reflect health- or disease-associated events connected
      to the adjacent or distant body regions of the fluid
      production/secretion/excretion and/or systemic reactions to the presence of
      disease. Sample collection and preparation is a critical step in order to obtain
      useful and valid information in clinical proteomics analysis. In this chapter, we
      present the current protocols and guidelines for human body fluid collection and
      storage, prior to proteomic analysis. A variety of body fluids that are currently
      being used in proteomic analysis and have potential interest in clinical practice
      are presented including blood plasma and serum, urine, cerebrospinal fluid,
      cerumen, nasal secretions, saliva, tears, breast milk, bronchoalveolar fluid,
      nipple aspirate fluid, amniotic fluid, bile, cervico-vaginal fluid, and seminal
      plasma. With no doubt these body fluids differ in the extent of their application
      in clinical proteomics investigations, hence in some cases the presented SOPs are
      established following more extensive testing (e.g., plasma, serum, urine, CSF)
      than others (nasal secretions, saliva, tears, breast milk, bronchoalveolar fluid,
      nipple aspirate fluid, amniotic fluid, bile, cervico-vaginal fluid, and seminal
      plasma). However, even in these latter cases, the presented protocols were
      reported by at least two independent groups according to the literature. We hope
      they can thus serve as a reliable guide for sample collection based on our
      current knowledge in the field and excellent starting points for proteomics
      investigators. It should also be pointed that variations to these protocols exist
      and their further refinement in the future is foreseen following the evolution of
      the proteomics technologies. 

PMID- 25384738
TI  - Targeting the proteome of cellular fractions: focus on secreted proteins.
AB  - The high complexity of the total cellular proteome underscores the need for a
      more targeted investigation of particular subcellular fractions as a means to
      detect the changes at the level of low abundance proteins. However, this approach
      requires the application of an enrichment strategy. In this chapter, we present
      the protocols, which have been used for the analysis of secretome from cell
      lines, targeting the investigation of protein expression changes. 

PMID- 25384739
TI  - Preparation of urinary exosomes: methodological issues for clinical proteomics.
AB  - Urinary exosomes are small (<100 nm) vesicles secreted into urine from renal
      epithelial cells. They are coated with lipid bilayer, they contain an array of
      membrane and cytosolic proteins, and selected RNA species, reflecting the
      molecular composition of their cell of origin. Thus, urinary exosomes have
      received considerable attention as potential biomarker source, as their proteomic
      analysis could lead to the discovery of new non-invasive site-specific biomarkers
      for renal diseases. Here, we describe a robust method for urinary exosome
      preparation, additional protocols for their biochemical characterization and for
      the quantitation of different preparations, to be used for comparative proteomic
      studies. 

PMID- 25384740
TI  - Sample treatment methods involving combinatorial peptide ligand libraries for
      improved proteomes analyses.
AB  - If used in an optimized manner, the technology of combinatorial peptide solid
      phase libraries can easily improve the analytical determinations of proteomes by
      several factors. The discovery of novel species and of early stage biomarkers
      becomes thus reachable with a simple sample treatment. This report describes the
      most important point to consider (overloading and full recovery) along with a
      minimum scientific background and gives then detailed recipes to laboratory
      technicians. Orientations for optional routes are also given according to the
      objective of the experimental investigations. This covers different approaches to
      capture proteins of very low abundance. Total protein harvestings to prevent
      partial losses are also described such as single exhaustive desorption and
      fractionated elutions for more detailed analyses. Documented results are also
      reported demonstrating the capability of the technology well beyond what is the
      common assumption.

PMID- 25384741
TI  - Glycoprotein enrichment method using a selective magnetic nano-probe platform
      (MNP) functionalized with lectins.
AB  - Protein post-translational modifications (PTMs) have increasingly become a
      research field of incredible importance to fully understand the regulation of
      biological processes in health and disease. Among PTMs, glycosylation is one of
      the most studied for which contributed the development and improvement of
      enrichment techniques. Nowadays, glycoprotein enrichment methods are based on
      lectin affinity, covalent interactions, and hydrophilic interaction liquid
      chromatography (HILIC). Nonetheless, the nanotechnology era has fetched new
      methods to enrich glycoproteins from complex samples as human biological fluids.
      For instance, magnetic nanoparticles (MNPs) are being used as an interesting
      enrichment approach allowing a better characterization of glycoproteins and
      glycopeptides.In this chapter, we describe an enrichment method based on MNPs
      functionalized with lectins (Concavalin A, wheat germ agglutinin, and Maackia
      amurensis lectin) to enrich specific sets of glycoproteins from biological
      fluids. Moreover, it is proposed a bioinformatic strategy to deal with data
      retrieved from mass spectrometry analysis of enriched samples aiming the
      identification of relevant biological processes modulated by a given stimuli and,
      ultimately, of new biomarkers for disease screening/management.

PMID- 25384742
TI  - The latest advancements in proteomic two-dimensional gel electrophoresis analysis
      applied to biological samples.
AB  - Two-dimensional gel electrophoresis (2DE) is one of the fundamental approaches in
      proteomics for the separation and visualization of complex protein mixtures.
      Proteins can be analyzed by 2DE using isoelectric focusing (IEF) in the first
      dimension, combined to sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) in the second dimension, gel staining (silver and Coomassie), image
      analysis, and 2DE gel database. High-resolution 2DE can resolve up to 5,000
      different proteins simultaneously (~2,000 proteins routinely), and detect and
      quantify <1 ng of protein per spot. Here, we describe the latest developments for
      a more complete analysis of biological fluids.

PMID- 25384743
TI  - 2DE maps in the discovery of human autoimmune kidney diseases: the case of
      membranous glomerulonephritis.
AB  - The identification of antigens in the autoimmune diseases is a primary point to
      elucidate the pathogenesis of disease. Here, we propose an "in vivo" proteomics
      approach to identify the antigens of auto-antibodies in membranous
      glomerulonephritis. In this approach, podocyte proteins resolved by two
      dimensional electrophoresis were semidry blotted to nitrocellulose membrane. Then
      the antibodies eluted from microdissected glomeruli and serum samples were used
      as a probe for the detection of podocyte antigens and characterized by means of
      mass spectrometry. These combined methods allowed us to identify six new antigens
      in membranous glomerulonephritis.

PMID- 25384744
TI  - MALDI-imaging mass spectrometry on tissues.
AB  - Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)-profiling
      and imaging mass spectrometry (MSI) are promising technologies for measuring
      hundreds of different molecules directly on tissues. For instance, small
      molecules, drugs and their metabolites, endogenous lipids, carbohydrates and
      complex peptides/proteins can be measured at the same time. In the most advanced
      instruments, it is achieved without significant disruption of sample integrity.
      MSI is a unique approach for assessing the spatial distribution of molecules
      using graphical multidimensional maps of their constituent analytes, which may
      for instance be correlated with histopathological alterations in patient tissues.
      MALDI-TOF-MSI technology has been implemented in hospitals of several countries,
      where it is routinely used for quick pathogen(s) identification, a task formerly
      accomplished by laborious and expensive DNA/RNA-based PCR (polymerase chain
      reaction) screening.In this chapter, we describe how MSI is performed, what is
      required from the researcher, the instrument vendors and finally what can be
      achieved with MSI. We restrict our descriptions only to MALDI-MSI although
      several other MS techniques of ionization can easily be linked to MSI. 

PMID- 25384745
TI  - Laser capture microdissection of fluorescently labeled amyloid plaques from
      Alzheimer's disease brain tissue for mass spectrometric analysis.
AB  - Laser capture microdissection (LCM) is used to isolate minute amounts of tissue
      for subsequent proteomics analysis. An advantage of this technique is that a
      specific subset of cells or tissue structures can be isolated and enriched from
      surrounding material. Here, we describe a LCM-based method for the isolation of
      amyloid plaques from the Alzheimer's disease (AD) brain using fluorescence and
      nano liquid chromatography (nLC) mass spectrometry (MS) analysis. Using this
      approach, we detect ~600 proteins in ~250 AD amyloid plaques.

PMID- 25384746
TI  - Urine sample preparation and fractionation for global proteome profiling by LC
      MS.
AB  - Urine has garnered tremendous interest over the past decade as a potential source
      of protein biomarkers for various pathologies. However, due to its low protein
      concentration and the presence of interfering compounds, urine constitutes a
      challenging analyte in proteomics. In the context of a project aimed at the
      discovery and evaluation of new candidate biomarkers of bladder cancer in urine,
      our laboratory has implemented and evaluated an array of preparation techniques
      for urinary proteome analysis. We present here the protocol that, in our hands,
      yielded the best overall proteome coverage with the lowest analytical effort. It
      begins with protein precipitation using trichloroacetic acid, in solution
      digestion and RP-C18 cartridge desalting of the resulting peptides mixture, and
      is followed by peptide fractionation by gel-free isoelectric focusing, and nano
      LC-MS/MS for database compilation. 

PMID- 25384747
TI  - Methods in capillary electrophoresis coupled to mass spectrometry for the
      identification of clinical proteomic/peptidomic biomarkers in biofluids.
AB  - Proteomic biomarkers hold the promise of enabling assessment of patients
      according to a pathological condition aiming at improvements in diagnosis,
      prognosis, in general clinical patient management. Capillary electrophoresis
      coupled to an electrospray ionization time-of-flight mass spectrometer (CE-MS)
      allows the detection of thousands of small proteins and peptides in various
      biofluids, in a single, reproducible and time-limited step, enabling the
      simultaneous comparison of multiple individual proteins and peptides in biomarker
      discovery, but also in clinical applications. The reliability of the CE-MS
      platform, together with the use of a validated approach for data processing and
      mining is, to date, the most advanced technique for biomarker discovery of
      clinical significance. In this chapter, we report on the materials, methods and
      protocols used for CE-MS-based clinical proteomics allowing the reproducible
      profiling of biofluids. 

PMID- 25384748
TI  - Quantification of proteins in urine samples using targeted mass spectrometry
      methods.
AB  - Numerous clinical proteomics studies are focused on the development of biomarkers
      to improve either diagnostics for early disease detection or the monitoring of
      the response to the treatment. Although, a wealth of biomarker candidates are
      available, their evaluation and validation in a true clinical setup remains
      challenging. In biomarkers evaluation studies, a panel of proteins of interest
      are systematically analyzed in a large cohort of samples. However, in spite of
      the latest progresses in mass spectrometry, the consistent detection of pertinent
      proteins in high complex biological samples is still a challenging task. Thus,
      targeted LC-MS/MS methods are better suited for the systematic analysis of
      biomarkers rather than shotgun approaches. This chapter describes the workflow
      used to perform targeted quantitative analyses of proteins in urinary samples.
      The peptides, as surrogates of the protein of interest, are commonly measured
      using a triple quadrupole mass spectrometers operated in selected reaction
      monitoring (SRM) mode. More recently, the advances in targeted LC-MS/MS analysis
      based on parallel reaction monitoring (PRM) performed on a quadrupole-orbitrap
      instrument have allowed to increase the specificity and selectivity of the
      measurements. 

PMID- 25384749
TI  - Statistical issues in the design and planning of proteomic profiling experiments.
AB  - The statistical design of a clinical proteomics experiment is a critical part of
      well-undertaken investigation. Standard concepts from experimental design such as
      randomization, replication and blocking should be applied in all experiments, and
      this is possible when the experimental conditions are well understood by the
      investigator. The large number of proteins simultaneously considered in proteomic
      discovery experiments means that determining the number of required replicates to
      perform a powerful experiment is more complicated than in simple experiments.
      However, by using information about the nature of an experiment and making simple
      assumptions this is achievable for a variety of experiments useful for biomarker
      discovery and initial validation. 

PMID- 25384750
TI  - Integrating proteomics profiling data sets: a network perspective.
AB  - Understanding disease mechanisms often requires complex and accurate integration
      of cellular pathways and molecular networks. Systems biology offers the
      possibility to provide a comprehensive map of the cell's intricate wiring
      network, which can ultimately lead to decipher the disease phenotype. Here, we
      describe what biological pathways are, how they function in normal and abnormal
      cellular systems, limitations faced by databases for integrating data, and
      highlight how network models are emerging as a powerful integrative framework to
      understand and interpret the roles of proteins and peptides in diseases. 

PMID- 25384751
TI  - The European Medicines Agency experience with biomarker qualification.
AB  - Since the launch of the qualification process in 2009, the CHMP reviewed/is
      reviewing 48 requests for qualification advice or opinion (as of Sept 2013)
      related to biomarkers (BM) or other novel drug development tools (e.g. patient
      reported outcome measures, modeling, and statistical methods). The qualification
      opinions are available on the EMA website (Qualification of novel methodologies
      for medicine development,
      http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/doc
      ment_listing_000319.jsp&mid=WC0b01ac0580022bb0#section2 , 2013). Also there is a
      trend of increasing numbers of qualification requests to CHMP, indicative of the
      pace that targeted drug development and personalized medicine is gaining and the
      need to bring the new tools from research to drug development and clinical use.
      This chapter will focus on the regulatory experience gained so far from the CHMP
      qualification procedure. Basic qualification principles will be presented.
      Through qualification examples, we will elaborate on common grounds and
      divergences between the different stakeholders.

PMID- 25384752
TI  - More stable and more efficient alternatives of Z-907: carbazole-based amphiphilic
      Ru(II) sensitizers for dye-sensitized solar cells.
AB  - Here we report two novel amphiphilic Ru(II) heteroleptic bipyridyl complexes, HD
      14 and HD-15, compared to previously reported NCSU-10. We have combined the
      strong electron donor characteristics of carbazole and the hydrophobic nature of
      different long alkyl chains, C7, C18 and C2 (NCSU-10), tethered to N-carbazole to
      study their influence on photocurrent, photovoltage and long term stability for
      dye-sensitized solar cells. Photon harvesting efficiency and electron donating
      characteristics of carbazole-based ancillary ligands were found to be unaffected
      by different alkyl chain lengths. However, a slight drop in the Voc of HD-14 and
      HD-15 was observed compared to that of NCSU-10. It was found by nanosecond flash
      photolysis transient absorption (TA) measurements that the faster the dye
      regeneration the higher the photocurrent density response, and the dye
      regeneration time was found to be 2.6, 3.6, and 3.7 MUs for HD-14, HD-15, and
      N719 dyes, respectively. The difference in the amplitude of the transient
      absorption (TA) signal of the oxidized dye as measured by femtosecond TA studies
      is in excellent agreement with the photocurrent generated, which was in the
      following order HD-14 > HD-15 > N719. Under 1000 h light soaking conditions, HD
      15 maintained up to 98% (only 2% loss) of the initial power conversion efficiency
      compared to 8% loss for HD-14 and 22% loss in the power conversion efficiency for
      NCSU-10. HD-15 was strikingly stable to light soaking conditions when employed in
      the presence of an ionic liquid electrolyte, which paves the way for widespread
      applications of dye-sensitized solar cells with long term stability. The total
      power conversion efficiency (eta) was 9.27% for HD-14 and 9.17% for HD-15
      compared to 8.92% for N719.

PMID- 25384753
TI  - Water and sediment quality, nutrient biochemistry and pollution loads in an urban
      freshwater lake: balancing human and ecological services.
AB  - Optimizing the utility of constructed waterways as residential development with
      water-frontage, along with a productive and functional habitat for wildlife is of
      considerable interest to managers. This study examines Lake Hugh Muntz, a large
      (17 ha) freshwater lake built in Gold Coast City, Australia. A ten year water
      quality monitoring programme shows that the lake has increasing nutrient
      concentrations, and together with summer algal blooms, the lake amenity as a
      popular recreational swimming and triathlon training location is at risk. A
      survey of fish and aquatic plant communities showed that the lake supports a sub
      set of species found in adjacent natural wetlands. Sediment contaminants were
      below the lower Australian trigger values, except As, Hg, Pb and Zn, probably a
      function of untreated and uncontrolled stormwater runoff from nearby urban roads.
      Sediment biogeochemistry showed early signs of oxygen depletion, and an increase
      in benthic organic matter decomposition and oxygen consumption will result in
      more nitrogen recycled to the water column as NH4(+) (increasing the intensity of
      summer algal blooms) and less nitrogen lost to the atmosphere as N2 gas via
      denitrification. A series of catchment restoration initiatives were modeled and
      the optimal stormwater runoff restoration effort needed for lake protection will
      be costly, particularly retrospective, as is the case here. Overall, balancing
      the lifestyles and livelihoods of residents along with ecosystem protection are
      possible, but require considerable trade-offs between ecosystem services and
      human use. 

PMID- 25384754
TI  - A review of amnestic MCI screening in east/southeast Asian older adults with low
      education: implications for early informant-clinician collaboration.
AB  - OBJECTIVE: The aim of this study is to review the recent literature on
      established cognitive tests and appropriate screening methods for amnestic mild
      cognitive impairment (MCI) in East/Southeast Asian older adults with a focus on
      those with low education. DESIGN: Peer-reviewed empirical studies conducted in
      Asia (China, Hong Kong, Japan, Korea, Singapore, and Taiwan) were identified
      using databases in psychology and medicine with combinations of the search terms
      "mild cognitive impairment," "dementia," "screening," "literacy," "illiteracy,"
      "low education," "informant," "family," "cognitive test," "memory complaints,"
      "activities of daily living," and "clinical dementia rating," limiting articles
      to those published in English since 1 January 2002. Of note, is that the term
      "amnestic mild cognitive impairment" was not used for searching the articles
      because the related cognitive impairment were often categorized non-specifically
      as MCI, but participants included those with amnestic cognitive challenges.
      Hence, the general term "MCI" has been used often throughout the text. RESULTS:
      Twelve studies that examined MCI screens were identified. An integrative approach
      using a combination of cognitive test and informant-based measure may be more
      sensitive or accurate than using any single screening method alone. CONCLUSION:
      MCI misdiagnosis may be prevalent, highlighting the need for early collaborative
      work between informants and clinicians to improve the accuracy of this diagnosis
      in older Asian adults with low education. Findings were suggestive, although
      restricted in generalizability even within similar cultural groups or neighboring
      regions. Clinical application is limited, but some findings provide guidance for
      future research.

PMID- 25384756
TI  - A novel bicompartmental mathematical model of glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common primary CNS neoplasm, and
      continues to have a dismal prognosis. A widely-used approach to the mathematical
      modeling of GBM involves utilizing a reaction-diffusion model of cell density as
      a function of space and time, which accounts for both the infiltrative nature of
      the tumor using a diffusion term, and the proliferation of tumor cells using a
      proliferation term. The current paper extends the standard models by
      incorporating an advection term to account for the so-called 'cell streaming'
      which is often seen with GBM, where some of the tumor cells seem to stream widely
      along the white matter pathways. The current paper introduces a bicompartmental
      GBM model in the form of coupled partial differential equations with a component
      of dispersive cells. The parameters needed for this model are explored. It is
      shown that this model can account for the rapid distant dispersal of GBM cells in
      the CNS, as well as such phenomena as multifocal gliomas with tumor foci distant
      from the core tumor site. The model suggests a higher percentage of tumor cells
      below the threshold of MRI images in comparison to the standard model. By
      incorporating an advection component, the proposed model is able to account for
      phenomena such as multicentric gliomas and rapid distant dispersion of a small
      fraction of tumor cells throughout the CNS, features important to the prognosis
      of GBM, but not easily accounted for by current models.

PMID- 25384755
TI  - Watching novice action degrades expert motor performance: causation between
      action production and outcome prediction of observed actions by humans.
AB  - Our social skills are critically determined by our ability to understand and
      appropriately respond to actions performed by others. However despite its obvious
      importance, the mechanisms enabling action understanding in humans have remained
      largely unclear. A popular but controversial belief is that parts of the motor
      system contribute to our ability to understand observed actions. Here, using a
      novel behavioral paradigm, we investigated this belief by examining a causal
      relation between action production, and a component of action understanding-
      outcome prediction, the ability of a person to predict the outcome of observed
      actions. We asked dart experts to watch novice dart throwers and predict the
      outcome of their throws. We modulated the feedbacks provided to them, caused a
      specific improvement in the expert's ability to predict watched actions while
      controlling the other experimental factors, and exhibited that a change
      (improvement) in their outcome prediction ability results in a progressive and
      proportional deterioration in the expert's own darts performance. This causal
      relationship supports involvement of the motor system in outcome prediction by
      humans of actions observed in others.

PMID- 25384757
TI  - Algal sulfated carrageenan inhibits proliferation of MDA-MB-231 cells via
      apoptosis regulatory genes.
AB  - Marine algae are prolific sources of sulfated polysaccharides, which may explain
      the low incidence of certain cancers in countries that traditionally consume
      marine food. Breast cancer is one of the most common types of non-skin cancer in
      females. In this study, extracted sulfated carrageenan (ESC), predominantly
      consisting of iota-carrageenan extracted from the red alga Laurencia papillosa,
      was characterized using Fourier transform infrared spectrometry. The biological
      effects of the identified extract were investigated and its potential cytotoxic
      activity was tested against the MDA-MB-231 cancer cell line. The biological
      biometer of the inhibitory concentration of the polysaccharide-treated MDA-MB-231
      cells was determined as 50 uM. Treatment with 50 uM ESC inhibited cell
      proliferation and promptly induced cell death through nuclear condensation and
      DNA fragmentation. Characterization of polysaccharide-treated MDA-MB-231 cell
      death revealed that induction of apoptosis occurred via the activation of the
      extrinsic apoptotic caspase-8 gene. The apoptotic signaling pathway was regulated
      through caspase-3, caspase-9, p53, Bax and Bcl-2 genes. These findings suggest
      that ESC may serve as a potential therapeutic agent to target breast cancer via
      prompting apoptosis.

PMID- 25384758
TI  - Evaluation of serum interleukin-6 level as a surrogate marker of synovial
      inflammation and as a factor of structural progression in early rheumatoid
      arthritis: results from a French national multicenter cohort.
AB  - OBJECTIVE: Interleukin-6 (IL-6) is a key cytokine in rheumatoid arthritis
      pathogenesis. We aimed to analyze the association between IL-6 serum levels and
      joint inflammation at baseline and the correlation of time-integrated IL-6 values
      with structural damage during the first 36 months of early arthritis. METHODS: IL
      6 was assessed by 2 different methods in 813 patients of the French early
      arthritis cohort ESPOIR (Etude et Suivi des Polyarthrites Indifferenciees
      Recentes) over 36 months. IL-6 and C-reactive protein (CRP) changes were
      correlated to radiographic progression assessed by the total Sharp/van der Heijde
      score (SHS). Synovium inflammation was assessed in a subgroup of 126 patients by
      ultrasonography (US). The relationship between SHS change and IL-6 or CRP levels
      at baseline was investigated by a univariate regression and a multivariable
      analysis. A longitudinal model nested by visit and patient was conducted to
      assess the role of IL-6 on SHS at each visit. RESULTS: At baseline, IL-6 was more
      strongly correlated with the swollen joint count than CRP level. In the
      univariate analysis, the time-integrated value of IL-6 was more strongly
      correlated with the swollen joint count and the variation of SHS than time
      integrated CRP level. Baseline IL-6 was not independently associated with SHS
      change. Longitudinal models nested by patient showed that IL-6 levels were
      associated with structural damage independently from the Disease Activity Score
      in 28 joints, smoking status, rheumatoid factor, and anti-citrullinated protein
      peptide antibody serology, treatments, and CRP levels. CONCLUSION: IL-6 level was
      a marker of US synovitis at baseline. Repeated measurements of IL-6 are
      associated with structural damage.

PMID- 25384759
TI  - Tuning soft nanostructures in self-assembled supramolecular gels: from morphology
      control to morphology-dependent functions.
AB  - Supramolecular gels are one kind of important soft material, in which small low
      molecular weight compounds self-assemble into various nanostructures through non
      covalent interactions to immobilize the solvents. While there are many important
      fundamental issues related to the gelation process, such as the design of the
      gelator, synergism of various non-covalent interactions between gelators, gelator
      solvents, the balances between gelation and crystallization and so on, the self
      assembled nanostructures forming during gelation are very interesting. These
      nanostructures have many unique features, such as the flexibility to respond to
      external stimuli, morphological diversity, ease of fabrication in large
      quantities, and so on. This review highlights some important features in tuning
      the nanostructures in the supramolecular gels from their morphological diversity,
      morphology control, morphology conversion, and morphology-depended functions. 

PMID- 25384760
TI  - Older Adults' Risk Practices From Hospital to Home: A Discourse Analysis.
AB  - PURPOSE: To understand risk-related practices of older adults returning home
      posthospitalization. RESEARCH DESIGN: Qualitative methods informed by critical
      discourse theory, designed to uncover linkages between broader social practices
      and peoples' talk and stories, were used. METHODS: Eight older adults, screened
      as high-risk from an inpatient cardiology unit, and six partners were interviewed
      face-to-face within three weeks of discharge. A discourse analysis of
      participants' accounts of risk was conducted: the cultural and social
      understandings or conceptual frameworks used to understand risk were identified.
      RESULTS: Ableism, a discourse in our society that privileges abledness, was found
      to permeate the data. Participants underscored that being abled was normal and
      being disabled was abnormal. Ableism, as a discourse or conceptual framework,
      compelled participants to appear and act abled, or to perform "compulsory
      abledness." That, in turn, produced their responses to risk: a pressure to
      preserve ableist identities created internal and external tensions related to
      objects and situations of risk and forced participants to use strategies to
      diminish and minimize risk. Participants created a new response-a position of
      "liminality" or in-between-where their accounts portrayed them as neither abled
      nor disabled. This discourse of liminality allowed them to reconcile tensions
      associated with risk. IMPLICATIONS: Critical discourse analysis sheds new light
      on older adults' risk practices. This approach challenges accepted ways of acting
      and thinking about what constitutes risk and produces possibilities for alternate
      ways of representing the same reality.

PMID- 25384761
TI  - Older People's Perspectives Regarding the Use of Sensor Monitoring in Their Home.
AB  - PURPOSE: The early detection of a decline in daily functioning of independently
      living older people can aid health care professionals in providing preventive
      interventions. To monitor daily activity patterns and, thereby detect a decline
      in daily functioning, new technologies, such as sensors can be placed in the home
      environment. The purpose of this qualitative study was to determine the
      perspectives of older people regarding the use of sensor monitoring in their
      daily lives. DESIGN AND METHODS: We conducted indepth, semistructured interviews
      with 11 persons between 68 and 93 years who had a sensor monitoring system
      installed in their home. The data were analyzed using Interpretative
      Phenomenological Analysis. RESULTS: The interviewed older persons positively
      valued sensor monitoring and indicated that the technology served as a strategy
      to enable independent living. The participants perceived that the system
      contributed to their sense of safety as an important premise for independent
      living. Some of the participants stated that it helped them to remain active. The
      potential privacy violation was not an issue for the participants. The
      participants considered that health care professionals' continuous access to
      their sensor data and use of the data for their safety outweighed the privacy
      concerns. IMPLICATIONS: These results provide new evidence that older persons
      experience sensor monitoring as an opportunity or strategy that contributes to
      independent living and that does not disturb their natural way of living. Based
      on this study, the development of new strategies to provide older people with
      access to their sensor data must be further explored.

PMID- 25384762
TI  - Restoration of spermatogenesis in infertile male chickens after transplantation
      of cryopreserved testicular cells.
AB  - 1. The aim of this study was to evaluate the ability of frozen-thawed testicular
      cells transplanted into infertile cocks to restore spermatogenesis and to compare
      two cryoprotectants (CPA) (dimethylsulfoxide (DMSO) and Biofreeze). 2. A total of
      24 infertile White Leghorn (WL) cocks were transplanted with cryopreserved
      testicular cells from fertile adult donor cocks. Both genetically close and
      phylogenetically distant chicken breeds were used as donor cocks. 3. Twelve out
      of 24 WL recipient cocks with cryopreserved testicular cells restored
      spermatogenesis within 2 months after the transplantation. Six out of 12
      recipient cocks with restored spermatogenesis successfully produced progeny
      expressing the donor phenotype. 4. There was no difference between the CPA in
      cell viability after thawing or in the number of offspring produced from
      cryopreserved testicular tissue. 5. The present work represents the first report
      of production of a donor-derived healthy progeny following frozen-thawed
      testicular cell transplantation in adult birds. The described results may
      contribute to preservation of endangered avian species and to maintaining their
      genetic variability.

PMID- 25384763
TI  - Onset rivalry: factors that succeed and fail to bias selection.
AB  - This project examined whether previous visual history can bias perceptual
      dominance during onset rivalry. A predictive sequence of non-rivalrous stimuli
      preceded dichoptically presented rivalrous displays. One of the dichoptic images
      was the implied next step of the preceding sequence while the other was not.
      Observers reported their initial dominant percept. Across five experiments, we
      found that motion sequences biased perceptual selection such that a rivalrous
      stimulus that continued a motion sequence tended to dominate one that did not.
      However, signals generated by complex pattern of motion information or verbal
      semantic information had no influence on selection. These results are consistent
      with the view that onset rivalry is an early phase of rivalry that is likely
      insensitive to modulation by factors originating beyond the visual system. 

PMID- 25384764
TI  - The human mycobiome.
AB  - Fungi are fundamental to the human microbiome, the collection of microbes
      distributed across and within the body, and the microbiome has been shown, in
      total, to modify fundamental human physiology, including energy acquisition,
      vitamin-cofactor availability, xenobiotic metabolism, immune development and
      function, and even neurological development and behavior. Here, a comprehensive
      review of current knowledge about the mycobiome, the collective of fungi within
      the microbiome, highlights methods for its study, diversity between body sites,
      and dynamics during human development, health, and disease. Early-stage studies
      show interactions between the mycobiome and other microbes, with host physiology,
      and in pathogenic and mutualistic phenotypes. Current research portends a vital
      role for the mycobiome in human health and disease. 

PMID- 25384765
TI  - Antifungal pharmacokinetics and pharmacodynamics.
AB  - Successful treatment of infectious diseases requires choice of the most suitable
      antimicrobial agent, comprising consideration of drug pharmacokinetics (PK),
      including penetration into infection site, pathogen susceptibility, optimal route
      of drug administration, drug dose, frequency of administration, duration of
      therapy, and drug toxicity. Antimicrobial pharmacokinetic/pharmacodynamic (PK/PD)
      studies consider these variables and have been useful in drug development,
      optimizing dosing regimens, determining susceptibility breakpoints, and limiting
      toxicity of antifungal therapy. Here the concepts of antifungal PK/PD studies are
      reviewed, with emphasis on methodology and application. The initial sections of
      this review focus on principles and methodology. Then the pharmacodynamics of
      each major antifungal drug class (polyenes, flucytosine, azoles, and
      echinocandins) is discussed. Finally, the review discusses novel areas of
      pharmacodynamic investigation in the study and application of combination
      therapy. 

PMID- 25384766
TI  - Innate Defense against Fungal Pathogens.
AB  - Human fungal infections have been on the rise in recent years and proved
      increasingly difficult to treat as a result of the lack of diagnostics, effective
      antifungal therapies, and vaccines. Most pathogenic fungi do not cause disease
      unless there is a disturbance in immune homeostasis, which can be caused by
      modern medical interventions, disease-induced immunosuppression, and naturally
      occurring human mutations. The innate immune system is well equipped to recognize
      and destroy pathogenic fungi through specialized cells expressing a broad range
      of pattern recognition receptors (PRRs). This review will outline the cells and
      PRRs required for effective antifungal immunity, with a special focus on the
      major antifungal cytokine IL-17 and recently characterized antifungal
      inflammasomes. 

PMID- 25384767
TI  - Treatment principles for Candida and Cryptococcus.
AB  - The yeasts Candida and Cryptococcus spp. are important human opportunistic
      pathogens. Candida spp. rely on skin or mucosal breach to cause bloodstream
      infection, whereas Cryptococcus spp. exploit depressed cell-mediated immunity
      characteristic of advanced HIV infection. The treatment for both organisms relies
      on the administration of rapidly fungicidal agents. In candidaemia, source
      control is important, with removal of prosthetic material and drainage of
      collections, as well as hunting for and tailoring therapy to disseminated sites
      of infection, particularly the eyes and heart. For cryptococcal meningitis,
      restoration of immune function through antiretroviral therapy (ART) is key,
      together with careful management of the complications of raised intracranial
      pressure and relapsed infection, both pre- and post-ART. 

PMID- 25384769
TI  - Fungal Pathogens: Survival and Replication within Macrophages.
AB  - The innate immune system is a critical line of defense against pathogenic fungi.
      Macrophages act at an early stage of infection, detecting and phagocytizing
      infectious propagules. To avoid killing at this stage, fungal pathogens use
      diverse strategies ranging from evasion of uptake to intracellular parasitism.
      This article will discuss five of the most important human fungal pathogens
      (Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Coccidiodes
      immitis, and Histoplasma capsulatum) and consider the strategies and virulence
      factors adopted by each to survive and replicate within macrophages. 

PMID- 25384768
TI  - Mechanisms of Antifungal Drug Resistance.
AB  - Antifungal therapy is a central component of patient management for acute and
      chronic mycoses. Yet, treatment choices are restricted because of the sparse
      number of antifungal drug classes. Clinical management of fungal diseases is
      further compromised by the emergence of antifungal drug resistance, which
      eliminates available drug classes as treatment options. Once considered a rare
      occurrence, antifungal drug resistance is on the rise in many high-risk medical
      centers. Most concerning is the evolution of multidrug- resistant organisms
      refractory to several different classes of antifungal agents, especially among
      common Candida species. The mechanisms responsible are mostly shared by both
      resistant strains displaying inherently reduced susceptibility and those
      acquiring resistance during therapy. The molecular mechanisms include altered
      drug affinity and target abundance, reduced intracellular drug levels caused by
      efflux pumps, and formation of biofilms. New insights into genetic factors
      regulating these mechanisms, as well as cellular factors important for stress
      adaptation, provide a foundation to better understand the emergence of antifungal
      drug resistance. 

PMID- 25384770
TI  - Evolutionary Perspectives on Human Fungal Pathogens.
AB  - Owing to their small size and paucity of phenotypic characters, progress in the
      evolutionary biology of microbes in general, and human pathogenic fungi in
      particular, has been linked to a series of advances in DNA sequencing over the
      past quarter century. Phylogenetics was the first area to benefit, with the
      achievement of a basic understanding of fungal phylogeny. Population genetics was
      the next advance, finding cryptic species everywhere, and recombination in
      species previously thought to be asexual. Comparative genomics saw the next
      advance, in which variation in gene content and changes in gene family size were
      found to be important sources of variation. Fungal population genomics is showing
      that gene flow among closely related populations and species provides yet another
      source of adaptive, genetic variation. Now, two means to associate genetic
      variation with phenotypic variation, "reverse ecology" for adaptive phenotypes,
      and genome-wide association of any phenotype, are letting evolutionary biology
      make a profound contribution to molecular developmental biology of pathogenic
      fungi. 

PMID- 25384771
TI  - Thermally Dimorphic Human Fungal Pathogens--Polyphyletic Pathogens with a
      Convergent Pathogenicity Trait.
AB  - Fungi are adept at changing their cell shape and developmental program in
      response to signals in their surroundings. Here we focus on a group of
      evolutionarily related fungal pathogens of humans known as the thermally
      dimorphic fungi. These organisms grow in a hyphal form in the environment but
      shift their morphology drastically within a mammalian host. Temperature is one of
      the main host signals that initiates their conversion to the "host" form and is
      sufficient in the laboratory to trigger establishment of this host-adapted
      developmental program. Here we discuss the major human pathogens in this group,
      which are Blastomyces dermatiditis, Coccidioides immitis/posadasii, Histoplasma
      capsulatum, Paracoccidioides brasiliensis/lutzii, Sporothrix schenckii, and
      Talaromyces marneffei (formerly known as Penicillium marneffei). The majority of
      these organisms are primary pathogens, with the ability to cause disease in
      healthy humans who encounter them in endemic areas. 

PMID- 25384772
TI  - Black Molds and Melanized Yeasts Pathogenic to Humans.
AB  - A review is given of melanized fungi involved in human infection, including
      species forming budding cells and strictly filamentous representatives.
      Classically, they are known as "phaeoid" or "dematiaceous" fungi, and, today,
      agents are recognized to belong to seven orders of fungi, of which the
      Chaetothyriales and Pleosporales are the most important. Infections range from
      cutaneous or pulmonary colonization to systemic or disseminated invasion.
      Subcutaneous involvement, either primary or after dissemination, may lead to host
      tissue proliferation of dermis or epidermis. Particularly in the Chaetothyriales,
      subcutaneous and systemic infections may occur in otherwise apparently healthy
      individuals. Infections are mostly chronic and require extended antifungal
      therapy and/or surgery. 

PMID- 25384773
TI  - Control of vascular smooth muscle function by Src-family kinases and reactive
      oxygen species in health and disease.
AB  - Reactive oxygen species (ROS) are now recognised as second messenger molecules
      that regulate cellular function by reversibly oxidising specific amino acid
      residues of key target proteins. Amongst these are the Src-family kinases
      (SrcFKs), a multi-functional group of non-receptor tyrosine kinases highly
      expressed in vascular smooth muscle (VSM). In this review we examine the evidence
      supporting a role for ROS-induced SrcFK activity in normal VSM contractile
      function and in vascular remodelling in cardiovascular disease. VSM contractile
      responses to G-protein-coupled receptor stimulation, as well as hypoxia in
      pulmonary artery, are shown to be dependent on both ROS and SrcFK activity.
      Specific phosphorylation targets are identified amongst those that alter
      intracellular Ca(2+) concentration, including transient receptor potential
      channels, voltage-gated Ca(2+) channels and various types of K(+) channels, as
      well as amongst those that regulate actin cytoskeleton dynamics and myosin
      phosphatase activity, including focal adhesion kinase, protein tyrosine kinase-2,
      Janus kinase, other focal adhesion-associated proteins, and Rho guanine
      nucleotide exchange factors. We also examine a growing weight of evidence in
      favour of a key role for SrcFKs in multiple pro-proliferative and anti-apoptotic
      signalling pathways relating to oxidative stress and vascular remodelling, with a
      particular focus on pulmonary hypertension, including growth-factor receptor
      transactivation and downstream signalling, hypoxia-inducible factors, positive
      feedback between SrcFK and STAT3 signalling and positive feedback between SrcFK
      and NADPH oxidase dependent ROS production. We also discuss evidence for and
      against the potential therapeutic targeting of SrcFKs in the treatment of
      pulmonary hypertension. 

PMID- 25384775
TI  - The effects of dexamethasone on post-asphyxial cerebral oxygenation in the
      preterm fetal sheep.
AB  - Exposure to clinical doses of the glucocorticoid dexamethasone increases brain
      activity and causes seizures in normoxic preterm fetal sheep without causing
      brain injury. In contrast, the same treatment after asphyxia increased brain
      injury. We hypothesised that increased injury was in part mediated by a mismatch
      between oxygen demand and oxygen supply. In preterm fetal sheep at 0.7 gestation
      we measured cerebral oxygenation using near-infrared spectroscopy,
      electroencephalographic (EEG) activity, and carotid blood flow (CaBF) from 24 h
      before until 72 h after asphyxia induced by 25 min of umbilical cord occlusion.
      Ewes received dexamethasone intramuscularly (12 mg 3 ml(-1)) or saline 15 min
      after the end of asphyxia. Fetuses were studied for 3 days after occlusion.
      During the first 6 h of recovery after asphyxia, dexamethasone treatment was
      associated with a significantly greater fall in CaBF (P < 0.05), increased
      carotid vascular resistance (P < 0.001) and a greater fall in cerebral
      oxygenation as measured by the difference between oxygenated and deoxygenated
      haemoglobin (delta haemoglobin; P < 0.05). EEG activity was similarly suppressed
      in both groups. From 6 to 10 h onward, dexamethasone treatment was associated
      with a return of CaBF to saline control levels, increased EEG power (P < 0.005),
      greater epileptiform transient activity (P < 0.001), increased oxidised
      cytochrome oxidase (P < 0.05) and an attenuated increase in [delta haemoglobin]
      (P < 0.05). In conclusion, dexamethasone treatment after asphyxia is associated
      with greater hypoperfusion in the critical latent phase, leading to impaired
      intracerebral oxygenation that may exacerbate neural injury after asphyxia.

PMID- 25384777
TI  - Contributions of white and brown adipose tissues and skeletal muscles to acute
      cold-induced metabolic responses in healthy men.
AB  - KEY POINTS: Both brown adipose tissue (BAT) and skeletal muscle activation
      contribute to the metabolic response of acute cold exposure in healthy men even
      under minimal shivering. Activation of adipose tissue intracellular lipolysis is
      associated with BAT metabolic response upon acute cold exposure in healthy men.
      Although BAT glucose uptake per volume of tissue is important, the bulk of
      glucose turnover during cold exposure is mediated by skeletal muscle metabolic
      activation even when shivering is minimized. ABSTRACT: Cold exposure stimulates
      the sympathetic nervous system (SNS), triggering the activation of cold-defence
      responses and mobilizing substrates to fuel the thermogenic processes. Although
      these processes have been investigated independently, the physiological
      interaction and coordinated contribution of the tissues involved in producing
      heat or mobilizing substrates has never been investigated in humans. Using [U
      (13)C]-palmitate and [3-(3)H]-glucose tracer methodologies coupled with positron
      emission tomography using (11)C-acetate and (18)F-fluorodeoxyglucose, we examined
      the relationship between whole body sympathetically induced white adipose tissue
      (WAT) lipolysis and brown adipose tissue (BAT) metabolism and mapped the skeletal
      muscle shivering and metabolic activation pattern during a mild, acute cold
      exposure designed to minimize shivering response in 12 lean healthy men. Cold
      induced increase in whole-body oxygen consumption was not independently
      associated with BAT volume of activity, BAT oxidative metabolism, or muscle
      metabolism or shivering intensity, but depended on the sum of responses of these
      two metabolic tissues. Cold-induced increase in non-esterified fatty acid (NEFA)
      appearance rate was strongly associated with the volume of metabolically active
      BAT (r = 0.80, P = 0.005), total BAT oxidative metabolism (r = 0.70, P = 0.004)
      and BAT glucose uptake (r = 0.80, P = 0.005), but not muscle glucose metabolism.
      The total glucose uptake was more than one order of magnitude greater in skeletal
      muscles compared to BAT during cold exposure (674 +/- 124 vs. 12 +/- 8 MUmol min(
      1), respectively, P < 0.001). Glucose uptake demonstrated that deeper, centrally
      located muscles of the neck, back and inner thigh were the greatest contributors
      of muscle glucose uptake during cold exposure due to their more important
      shivering response. In summary, these results demonstrate for the first time that
      the increase in plasma NEFA appearance from WAT lipolysis is closely associated
      with BAT metabolic activation upon acute cold exposure in healthy men. In humans,
      muscle glucose utilization during shivering contributes to a much greater extent
      than BAT to systemic glucose utilization during acute cold exposure.

PMID- 25384780
TI  - Recruitment of Gbetagamma controls the basal activity of G-protein coupled
      inwardly rectifying potassium (GIRK) channels: crucial role of distal C terminus
      of GIRK1.
AB  - The G-protein coupled inwardly rectifying potassium (GIRK, or Kir3) channels are
      important mediators of inhibitory neurotransmission via activation of G-protein
      coupled receptors (GPCRs). GIRK channels are tetramers comprising combinations of
      subunits (GIRK1-4), activated by direct binding of the Gbetagamma subunit of Gi/o
      proteins. Heterologously expressed GIRK1/2 exhibit high, Gbetagamma-dependent
      basal currents (Ibasal) and a modest activation by GPCR or coexpressed
      Gbetagamma. Inversely, the GIRK2 homotetramers exhibit low Ibasal and strong
      activation by Gbetagamma. The high Ibasal of GIRK1 seems to be associated with
      its unique distal C terminus (G1-dCT), which is not present in the other
      subunits. We investigated the role of G1-dCT using electrophysiological and
      fluorescence assays in Xenopus laevis oocytes and protein interaction assays. We
      show that expression of GIRK1/2 increases the plasma membrane level of
      coexpressed Gbetagamma (a phenomenon we term 'Gbetagamma recruitment') but not of
      coexpressed Galphai3. All GIRK1-containing channels, but not GIRK2 homomers,
      recruited Gbetagamma to the plasma membrane. In biochemical assays, truncation of
      G1-dCT reduces the binding between the cytosolic parts of GIRK1 and Gbetagamma,
      but not Galphai3. Nevertheless, the truncation of G1-dCT does not impair
      activation by Gbetagamma. In fluorescently labelled homotetrameric GIRK1 channels
      and in the heterotetrameric GIRK1/2 channel, the truncation of G1-dCT abolishes
      Gbetagamma recruitment and decreases Ibasal. Thus, we conclude that G1-dCT
      carries an essential role in Gbetagamma recruitment by GIRK1 and, consequently,
      in determining its high basal activity. Our results indicate that G1-dCT is a
      crucial part of a Gbetagamma anchoring site of GIRK1-containing channels,
      spatially and functionally distinct from the site of channel activation by
      Gbetagamma.

PMID- 25384782
TI  - The determinants of transverse tubular volume in resting skeletal muscle.
AB  - The transverse tubular (t)-system of skeletal muscle couples sarcolemmal
      electrical excitation with contraction deep within the fibre. Exercise, pathology
      and the composition of the extracellular fluid (ECF) can alter t-system volume (t
      volume). T-volume changes are thought to contribute to fatigue, rhabdomyolysis
      and disruption of excitation-contraction coupling. However, mechanisms that
      underlie t-volume changes are poorly understood. A multicompartment, history
      independent computer model of rat skeletal muscle was developed to define the
      minimum conditions for t-volume stability. It was found that the t-system tends
      to swell due to net ionic fluxes from the ECF across the access resistance.
      However, a stable t-volume is possible when this is offset by a net efflux from
      the t-system to the cell and thence to the ECF, forming a net ion cycle ECF->t
      system->sarcoplasm->ECF that ultimately depends on Na(+)/K(+)-ATPase activity.
      Membrane properties that maximize this circuit flux decrease t-volume, including
      PNa(t) > PNa(s), PK(t) < PK(s) and N(t) < N(s) [P, permeability; N, Na(+)/K(+)
      ATPase density; (t), t-system membrane; (s), sarcolemma]. Hydrostatic pressures,
      fixed charges and/or osmoles in the t-system can influence the magnitude of t
      volume changes that result from alterations in this circuit flux. Using a
      parameter set derived from literature values where possible, this novel theory of
      t-volume was tested against data from previous experiments where t-volume was
      measured during manipulations of ECF composition. Predicted t-volume changes
      correlated satisfactorily. The present work provides a robust, unifying
      theoretical framework for understanding the determinants of t-volume.

PMID- 25384783
TI  - Pannexin channels and ischaemia.
AB  - An ischaemic stroke occurs during loss of blood flow in the brain from the
      occlusion of a blood vessel. The ischaemia itself comprises a complex array of
      insults, including oxygen and glucose deprivation (OGD), glutamate
      excitotoxicity, acidification/hypercapnia, and loss of sheer forces. A
      substantial amount of knowledge has accumulated that define the excitotoxic
      cascade downstream of N-methyl-d-aspartate receptors (NMDARs). While the NMDAR
      can influence numerous downstream elements, one critical target during ischaemia
      is the ion channel, pannexin-1 (Panx1). The C-terminal region of Panx1 appears
      critical for its regulation under a host of physiological and pathological
      stimuli. We have shown using hippocampal brain slices that Panx1 is activated by
      NMDARs through Src family kinases. However, it is not yet certain if this
      involves direct phosphorylation of Panx1 or an allosteric interaction between the
      channel's C-terminal tail and Src. Interestingly, Panx1 opening during ischaemia
      and NMDAR over-activation is antagonized by an interfering peptide that comprises
      amino acids 305-318 of Panx1. Thus, targeting the activation of Panx1 by NMDARs
      and Src kinases is an attractive mechanism to reduce anoxic depolarizations and
      neuronal death. 

PMID- 25384785
TI  - Defining inhibitory neurone function in respiratory circuits: opportunities with
      optogenetics?
AB  - Pharmacological and mathematical modelling studies support the view that synaptic
      inhibition in mammalian brainstem respiratory circuits is essential for
      generating normal and stable breathing movements. GABAergic and glycinergic
      neurones are known components of these circuits but their precise functional
      roles have not been established, especially within key microcircuits of the
      respiratory pre-Botzinger (pre-BotC) and Botzinger (BotC) complexes involved in
      phasic control of respiratory pump and airway muscles. Here, we review briefly
      current concepts of relevant complexities of inhibitory synapses and the
      importance of synaptic inhibition in the operation of these microcircuits. We
      highlight results and limitations of classical pharmacological studies that have
      suggested critical functions of synaptic inhibition. We then explore the
      potential opportunities for optogenetic strategies that represent a promising new
      approach for interrogating function of inhibitory circuits, including a
      hypothetical wish list for optogenetic approaches to allow expedient application
      of this technology. We conclude that recent technical advances in optogenetics
      should provide a means to understand the role of functionally select and
      regionally confined subsets of inhibitory neurones in key respiratory circuits
      such as those in the pre-BotC and BotC. 

PMID- 25384788
TI  - Vitamin C and E supplementation alters protein signalling after a strength
      training session, but not muscle growth during 10 weeks of training.
AB  - This study investigated the effects of vitamin C and E supplementation on acute
      responses and adaptations to strength training. Thirty-two recreationally
      strength-trained men and women were randomly allocated to receive a vitamin C and
      E supplement (1000 mg day(-1) and 235 mg day(-1), respectively), or a placebo,
      for 10 weeks. During this period the participants' training involved heavy-load
      resistance exercise four times per week. Muscle biopsies from m. vastus lateralis
      were collected, and 1 repetition maximum (1RM) and maximal isometric voluntary
      contraction force, body composition (dual-energy X-ray absorptiometry), and
      muscle cross-sectional area (magnetic resonance imaging) were measured before and
      after the intervention. Furthermore, the cellular responses to a single exercise
      session were assessed midway in the training period by measurements of muscle
      protein fractional synthetic rate and phosphorylation of several hypertrophic
      signalling proteins. Muscle biopsies were obtained from m. vastus lateralis twice
      before, and 100 and 150 min after, the exercise session (4 * 8RM, leg press and
      knee-extension). The supplementation did not affect the increase in muscle mass
      or the acute change in protein synthesis, but it hampered certain strength
      increases (biceps curl). Moreover, increased phosphorylation of p38 mitogen
      activated protein kinase, Extracellular signal-regulated protein kinases 1 and 2
      and p70S6 kinase after the exercise session was blunted by vitamin C and E
      supplementation. The total ubiquitination levels after the exercise session,
      however, were lower with vitamin C and E than placebo. We concluded that vitamin
      C and E supplementation interfered with the acute cellular response to heavy-load
      resistance exercise and demonstrated tentative long-term negative effects on
      adaptation to strength training.

PMID- 25384789
TI  - Microvascular perfusion heterogeneity contributes to peripheral vascular disease
      in metabolic syndrome.
AB  - A major challenge facing public health is the increased incidence and prevalence
      of the metabolic syndrome, a clinical condition characterized by excess
      adiposity, impaired glycaemic control, dyslipidaemia and moderate hypertension.
      The greatest concern for this syndrome is the profound increase in risk for
      development of peripheral vascular disease (PVD) in afflicted persons. However,
      ongoing studies suggest that reductions in bulk blood flow to skeletal muscle may
      not be the primary contributor to the premature muscle fatigue that is a hallmark
      of PVD. Compelling evidence has been provided suggesting that an increasingly
      spatially heterogeneous and temporally stable distribution of blood flow at
      successive arteriolar bifurcations in metabolic syndrome creates an environment
      where a large number of the pre-capillary arterioles have low perfusion, low
      haematocrit, and are increasingly confined to this state, with limited ability to
      adapt perfusion in response to a challenged environment. Single pharmacological
      interventions are unable to significantly restore function owing to a divergence
      in their spatial effectiveness, although combined therapeutic approaches to
      correct adrenergic dysfunction, elevated oxidant stress and increased thromboxane
      A2 improve perfusion-based outcomes. Integrated, multi-target therapeutic
      interventions designed to restore healthy network function and flexibility may
      provide for superior outcomes in subjects with metabolic syndrome-associated PVD.

PMID- 25384790
TI  - Alternating membrane potential/calcium interplay underlies repetitive focal
      activity in a genetic model of calcium-dependent atrial arrhythmias.
AB  - KEY POINTS: Atrial fibrillation is often initiated and perpetuated by abnormal
      electrical pulses repetitively originating from regions outside the heart's
      natural pacemaker. In this study we examined the causal role of abnormal calcium
      releases from the sarcoplasmic reticulum in producing repetitive electrical
      discharges in atrial cells and tissues. Calsequestrin2 is a protein that
      stabilizes the closed state of calcium release channels, i.e. the ryanodine
      receptors. In the atria from mice predisposed to abnormal calcium releases
      secondary to the absence of calsequestrin2, we observed abnormal repetitive
      electrical discharges that may lead to atrial fibrillation. Here, we report a
      novel pathological rhythm generator. Specifically, abnormal calcium release leads
      to electrical activation, which in turn results in another abnormal calcium
      release. This process repeats itself and thus sustains the repetitive electrical
      discharges. These results suggest that improving the stability of ryanodine
      receptors might be useful to treat atrial fibrillation. ABSTRACT: Aberrant
      diastolic calcium (Ca) release due to leaky ryanodine receptors (RyR2s) has been
      recently associated with atrial fibrillation (AF) and catecholaminergic
      polymorphic ventricular tachycardia (CPVT). However, it remains unclear how
      diastolic Ca release contributes to the rising of rapid repetitive focal
      activity, which is considered as a common AF triggering mechanism. To address
      this question, we conducted simultaneous voltage/Ca optical mapping in atrial
      tissue and one-/two-dimensional confocal imaging in atrial tissue and myocytes
      from wild-type (WT, n = 15) and CPVT mice lacking calsequestrin 2 (Casq2(-/-), n
      = 45), which promotes diastolic Ca release. During beta-adrenergic stimulation
      (100 nM isoproterenol), only Casq2(-/-) atrial myocytes showed pacing-induced
      self-sustained repetitive activity (31 +/- 21 s vs. none in WT). Importantly, in
      atrial tissue, this repetitive activity could translate to Ca-dependent focal
      arrhythmia. Ectopic action potential (AP) firing during repetitive activity
      occurred only when diastolic Ca release achieved a sufficient level of
      synchronization. The AP, in turn, synchronized subsequent diastolic Ca release by
      temporally aligning multiple sources of Ca waves both within individual myocytes
      and throughout the atrial tissue. This alternating interplay between AP and
      diastolic Ca release perpetuates the self-sustaining repetitive activity. In
      fact, pharmacological disruption of synchronized diastolic Ca release (by
      ryanodine) prevented aberrant APs; and vice versa, the inhibition of AP (by TTX
      or 0 Na, 0 Ca solution) de-synchronized diastolic Ca release. Taken together,
      these results suggest that a cyclical interaction between synchronized diastolic
      Ca release and AP forms a pathological rhythm generator that is involved in Ca
      dependent atrial arrhythmias in CPVT.

PMID- 25384797
TI  - Effects of environmental sounds on the guessability of animated graphic symbols.
AB  - Graphic symbols are a necessity for pre-literate children who use aided
      augmentative and alternative communication (AAC) systems (including non
      electronic communication boards and speech generating devices), as well as for
      mobile technologies using AAC applications. Recently, developers of the Autism
      Language Program (ALP) Animated Graphics Set have added environmental sounds to
      animated symbols representing verbs in an attempt to enhance their iconicity. The
      purpose of this study was to examine the effects of environmental sounds (added
      to animated graphic symbols representing verbs) in terms of naming. Participants
      included 46 children with typical development between the ages of 3;0 to 3;11
      (years;months). The participants were randomly allocated to a condition of
      symbols with environmental sounds or a condition without environmental sounds.
      Results indicated that environmental sounds significantly enhanced the naming
      accuracy of animated symbols for verbs. Implications in terms of symbol
      selection, symbol refinement, and future symbol development will be discussed.

PMID- 25384794
TI  - Impact of alpha-fetoprotein on hepatocellular carcinoma development during
      entecavir treatment of chronic hepatitis B virus infection.
AB  - BACKGROUND: Entecavir (ETV) is one of the first-line nucleoside analogs for
      treating patients with chronic hepatitis B virus (HBV) infection. However, the
      hepatocellular carcinoma (HCC) risk for ETV-treated patients remains unclear.
      METHODS: A total of 496 Japanese patients with chronic HBV infection undergoing
      ETV treatment were enrolled in this study. The baseline characteristics were as
      follows: age 52.6 +/- 12.0 years, males 58%, positive for hepatitis B e antigen
      45 %, cirrhosis 19%, and median HBV DNA level 6.9 log copies (LC) per milliliter.
      The mean treatment duration was 49.9 +/- 17.5 months. RESULTS: The proportions of
      HBV DNA negativity (below 2.6 LC/mL) were 68% at 24 weeks and 86% at 1 year, and
      the rates of alanine aminotransferase (ALT) level normalization were 62 and 72%,
      respectively. The mean serum alpha-fetoprotein (AFP) levels decreased
      significantly at 24 weeks after ETV treatment initiation (from 29.0 +/- 137.1 to
      5.7 +/- 27.9 ng/mL, p < 0.001). The cumulative incidence of HCC at 3, 5, and 7
      years was 6.0, 9.6, and 17.2%, respectively, among all enrolled patients. In a
      multivariate analysis, advanced age [55 years or older, hazard ratio (HR) 2.84; p
      = 0.018], cirrhosis (HR 5.59, p < 0.001), and a higher AFP level (10 ng/mL or
      greater) at 24 weeks (HR 2.38, p = 0.034) were independent risk factors for HCC
      incidence. HCC incidence was not affected by HBV DNA negativity or by ALT level
      normalization at 24 weeks. CONCLUSIONS: The AFP level at 24 weeks after ETV
      treatment initiation can be the on-treatment predictive factor for HCC incidence
      among patients with chronic HBV infection.

PMID- 25384798
TI  - Photopatterning of hydrogel scaffolds coupled to filter materials using
      stereolithography for perfused 3D culture of hepatocytes.
AB  - In vitro models that recapitulate the liver's structural and functional
      complexity could prolong hepatocellular viability and function to improve
      platforms for drug toxicity studies and understanding liver pathophysiology.
      Here, stereolithography (SLA) was employed to fabricate hydrogel scaffolds with
      open channels designed for post-seeding and perfused culture of primary
      hepatocytes that form 3D structures in a bioreactor. Photopolymerizable
      polyethylene glycol-based hydrogels were fabricated coupled to chemically
      activated, commercially available filters (polycarbonate and polyvinylidene
      fluoride) using a chemistry that permitted cell viability, and was robust enough
      to withstand perfused culture of up to 1 uL/s for at least 7 days. SLA energy
      dose, photoinitiator concentrations, and pretreatment conditions were screened to
      determine conditions that maximized cell viability and hydrogel bonding to the
      filter. Multiple open channel geometries were readily achieved, and included
      ellipses and rectangles. Rectangular open channels employed for subsequent
      studies had final dimensions on the order of 350 um by 850 um. Cell seeding
      densities and flow rates that promoted cell viability were determined. Perfused
      culture of primary hepatocytes in hydrogel scaffolds in the presence of soluble
      epidermal growth factor (EGF) prolonged the maintenance of albumin production
      throughout the 7-day culture relative to 2D controls. This technique of bonding
      hydrogel scaffolds can be employed to fabricate soft scaffolds for a number of
      bioreactor configurations and applications.

PMID- 25384800
TI  - Case of adult-onset type II citrullinemia treated as schizophrenia for a long
      time.

PMID- 25384799
TI  - System xC- is a mediator of microglial function and its deletion slows symptoms
      in amyotrophic lateral sclerosis mice.
AB  - Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease
      and evidence from mice expressing amyotrophic lateral sclerosis-causing SOD1
      mutations suggest that neurodegeneration is a non-cell autonomous process where
      microglial cells influence disease progression. However, microglial-derived
      neurotoxic factors still remain largely unidentified in amyotrophic lateral
      sclerosis. With excitotoxicity being a major mechanism proposed to cause motor
      neuron death in amyotrophic lateral sclerosis, our hypothesis was that excessive
      glutamate release by activated microglia through their system [Formula: see text]
      (a cystine/glutamate antiporter with the specific subunit xCT/Slc7a11) could
      contribute to neurodegeneration. Here we show that xCT expression is enriched in
      microglia compared to total mouse spinal cord and absent from motor neurons.
      Activated microglia induced xCT expression and during disease, xCT levels were
      increased in both spinal cord and isolated microglia from mutant SOD1 amyotrophic
      lateral sclerosis mice. Expression of xCT was also detectable in spinal cord post
      mortem tissues of patients with amyotrophic lateral sclerosis and correlated with
      increased inflammation. Genetic deletion of xCT in mice demonstrated that
      activated microglia released glutamate mainly through system [Formula: see text].
      Interestingly, xCT deletion also led to decreased production of specific
      microglial pro-inflammatory/neurotoxic factors including nitric oxide, TNFa and
      IL6, whereas expression of anti-inflammatory/neuroprotective markers such as
      Ym1/Chil3 were increased, indicating that xCT regulates microglial functions. In
      amyotrophic lateral sclerosis mice, xCT deletion surprisingly led to earlier
      symptom onset but, importantly, this was followed by a significantly slowed
      progressive disease phase, which resulted in more surviving motor neurons. These
      results are consistent with a deleterious contribution of microglial-derived
      glutamate during symptomatic disease. Therefore, we show that system [Formula:
      see text] participates in microglial reactivity and modulates amyotrophic lateral
      sclerosis motor neuron degeneration, revealing system [Formula: see text]
      inactivation, as a potential approach to slow amyotrophic lateral sclerosis
      disease progression after onset of clinical symptoms. 

PMID- 25384801
TI  - Data for improvement and clinical excellence: report of an interrupted time
      series trial of feedback in long-term care.
AB  - BACKGROUND: There is considerable evidence about the effectiveness of audit
      coupled with feedback for provider behavior change, although few feedback
      interventions have been conducted in long-term care settings. The primary purpose
      of the Data for Improvement and Clinical Excellence-Long-Term Care (DICE-LTC)
      project was to assess the effects of a feedback intervention delivered to all
      direct care providers on resident outcomes. Our objective in this report is to
      assess the effect of feedback reporting on rates of pain assessment, depression
      screening, and falls over time. METHODS: The intervention consisted of monthly
      feedback reports delivered to all direct care providers, facility and unit
      administrators, and support staff, delivered over 13 months in nine LTC units
      across four facilities. Data for feedback reports came from the Resident
      Assessment Instrument Minimum Data Set (RAI) version 2.0, a standardized
      instrument mandated in LTC facilities throughout Alberta. The primary evaluation
      used an interrupted time series design with a comparison group (units not
      included in the feedback intervention) and a comparison condition (pressure
      ulcers). We used segmented regression analysis to assess the effect of the
      feedback intervention. RESULTS: The primary outcome of the study, falls, showed
      little change over the period of the intervention, except for a small increase in
      the rate of falls during the intervention period. The only outcome that improved
      during the intervention period was the proportion of residents with high pain
      scores, which decreased at the beginning of the intervention. The proportion of
      residents with high depression scores appeared to worsen during the intervention.
      CONCLUSIONS: Maintaining all nine units in the study for its 13-month duration
      was a positive outcome. The feedback reports, without any other intervention
      included, did not achieve the desired reduction in proportion of falls and
      elevated depression scores. The survey on intention to change pain assessment
      practice which was conducted shortly after most of the feedback distribution
      cycles may have acted as a co-intervention supporting a reduction in pain scores.
      The processing and delivery of feedback reports could be accomplished at
      relatively low cost because the data are mandated and could be added to other
      intervention approaches to support implementation of evidence-based practices.

PMID- 25384802
TI  - Coexistence mechanisms at multiple scales in mosquito assemblages.
AB  - BACKGROUND: Species coexistence in mosquito assemblages may depend on mechanisms
      related to interspecific resource partitioning occurring at multiple scales. In
      the present work we investigated co-occurrence or spatial segregation in mosquito
      assemblages sharing resources at micro-habitat, habitat and landscape scales.
      Environmental characteristics, mosquito fauna as adults and larvae were assessed
      along vegetation gradient in a natural landscape of tropical rainforest. Huisman
      Olff-Fresco (HOF) and Generalized Additive (GAM) models were employed to explore
      relationships between abundances of potential competitors in mosquito assemblages
      and vegetation gradient (e.g., scrublands, mixed arboreal vegetation and dense
      ombrophilous forest). We tested hypotheses concerning mosquito species co
      occurrence or spatial segregation employing binomial logistic regression models.
      RESULTS: Co-occurrences and spatial segregation of mosquito species showed
      evidences of three scales of coexistence mechanisms: 1) micro-habitat--scale 1:
      different behaviors in response to food availability in specific vertical strata
      within larval container; 2) habitat--scale 2: specialized strategies related to
      heterogeneity of resource availability among larval containers and 3) landscape-
      scale 3: asymmetrical competition dependent upon the context of abiotic and
      biotic variables. CONCLUSION: Results of the present work suggest that
      coexistence mechanisms can concomitantly work at multiple scales.

PMID- 25384803
TI  - Gastrointestinal damage by non-steroidal anti-inflammatory drugs: updated
      clinical considerations.
AB  - Gastrointestinal (GI) damage by non-steroidal anti-inflammatory drugs (NSAIDs) is
      an important Public Health problem due to morbility and elevated mortality rate.
      The logic behind the development and sale of molecules which are selective
      cyclooxegnase-2 (COX-2) inhibitors called coxibs, is to limit the undesired
      effects of traditional NSAIDs, which should theoretically derive from the
      inhibition of COX-1. With respect to the emphasis of the initial trials, to now
      epidemiological studies, open-label studies, meta-analyses and reviews of the
      same data with longer follow-up, have produced opposite conclusions. Indeed, a
      recent series of meta-analyses has shown that the risks of GI events are similar
      for coxib and diclofenac, while they are significantly higher during the
      assumption of ibuprofen or naproxen. Moreover, the presumed lower gastrolesivity
      of coxibs is based on a highly simplified hypothesis, that the gastroprotective
      PGs derive from COX-1 and that the phlogistic processes are related to COX-2.
      Also in geriatric populations, though less tolerated than coxibs, diclofenac
      presents minor GI side effects when compared with naproxen and ibuprofen. In this
      context, in the case of moderate pain intensity, it is possible to use
      combinations with weak opioids, such as paracetamol-tramadol. Though intestinal
      damage by NSAIDs are a nosological entity of growing interest, to now no trial
      has been conducted with optimal criteria to demonstrate the superiority of coxibs
      over traditional NSAIDs. For this reason, chronic inflammation of the intestine
      still represents a contraindication to the administration of coxibs. 

PMID- 25384804
TI  - Benefit of supplements in functional dyspepsia after treatment of Helicobacter
      pylori.
AB  - AIM: Functional dyspepsia, though benign, leads to deterioration of the quality
      of life and high costs for healthcare systems. The optimal therapy for functional
      dyspepsia is still to be defined because of its multifactorial pathogenesis. In
      an open multicentric study of patients with functional dyspepsia, we
      prospectively evaluated the benefit of treatment with a food supplement composed
      of sodium alginate, carbonate calcium, pineapple, papaya, ginger, alpha
      galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy). METHODS: Ninety
      one consecutive patients were included, suffering from functional dyspepsia, who
      had been previously submitted to therapy to eradicate the infection from
      Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test
      (UBT). The primary goal was to establish the percentage of patients who continued
      to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT,
      differentiating between patients who were treated (N.=55) with Perdiges and those
      who were not (N.=36). Our secondary goal was to document the differences within
      the 2 groups in terms of symptoms perceived between the start and end of the
      observation period. The wellness reported, during or in absence of treatment with
      Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale)
      completed before the start of the treatment and after 30 days. RESULTS: All the
      patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were
      not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The
      VAS scale of those who took Perdiges improved on average by 1.78 points versus a
      worsening of 0.08 points of those who did not take it (P<0.0001). Furthermore,
      while among those who took Perdiges there was a statistically significant
      improvement (P<0.0001) in the VAS scale, between the baseline and the end of
      treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who
      did not take it. CONCLUSION: Perdiges is significantly effective in the period
      following treatment to eradicate the infection from H. pylori in patients with
      functional dyspepsia. This allows to reduce the need to use antisecretive drugs.
      Further randomised studies, with wide ranging case histories, must assess its
      long-term efficacy.

PMID- 25384805
TI  - Adherence to medical treatment in inflammatory bowel disease patients.
AB  - AIM: Inflammatory bowel diseases (IBD) are a group of chronic intestinal
      conditions characterized by unpredictable course, with periods of flare-ups and
      remissions suggesting poor adherence to medical therapy. On the other hand
      adherence is one of the most common reason of failure in the treatment of chronic
      disease. METHODS: We have analyzed IBD patients' questionnaires, sent by IBD
      Society of Emilia-Romagna Region (Italy). The anonymous questionnaire included
      sex, age, qualification, management, disease duration, disease associated,
      previous surgery, use of homeopathy and self-medication and possible
      psychological support. We classified patients based on IBD type: Crohn's disease
      (CD) and ulcerative colitis (UC). RESULTS: A total of 559 IBD patients were
      analysed (50.1% female), 52.8% were affected by CD. Patients were followed by
      gastroenterologist in 84.7% of cases. 17.4% of patient reported non-adherence to
      medical therapy; univariate analysis showed that non-adherence was more frequent
      in young females followed-up by general practitioners, no difference was found in
      educational status or type of IBD. Factors independently associated with greater
      adherence to medical therapy were age (OR=2.039) and follow-up by
      gastroenterologist (OR=3.025). CONCLUSION: Non-adherence should be taken into
      account in IBD patients and especially in young female. Gastroenterologists have
      a major role in promoting education.

PMID- 25384806
TI  - Long term course of ulcerative colitis in the prebiologic era. A retrospective
      study in a tertiary referral center.
AB  - AIM: Several population-based studies have shown that long term prognosis of
      ulcerative colitis (UC) may be better than previously reported. The aim of this
      study was to evaluate the course of UC in a referral center cohort in the pre
      biologic era and to identify possible prognostic factors. METHODS: All patients
      with established diagnosis of UC have been extracted from our GI Unit IBD
      Database. Clinical and demographic characteristics of all patients were recorded
      at the time of diagnosis. The disease course was retrospectively evaluated
      considering four primary end points: change in disease extension, need of
      corticosteroids, need of immunomodulators, and need of colectomy. The Kaplan
      Meier survival method was used to estimate the cumulative probability of a course
      free of the outcome of interest. RESULTS: Eight hundred and seven UC patients
      diagnosed between 1984 and 2008 have been included: 21.8% had proctitis, 47.6%
      had distal colitis and 30.6% had extensive colitis. The median follow up after
      diagnosis was 91 months (range 12-596). The probability of extension of proctitis
      within 10 years was 39.7%. In the whole cohort, the 10 years probability of
      receiving corticosteroids and immunomodulators was 46.7% and 12.4%, respectively.
      The 10-year probability of colectomy was 6.5%. Extensive colitis was associated
      with a higher probability of receiving corticosteroids, immunomodulators and
      surgery. CONCLUSION: Long-term prognosis of UC is favourable for the majority of
      patients. Extensive colitis is the most relevant negative prognostic factor.
      Results from our referral center study are similar to that reported in population
      based studies. Further studies are required to assess the possible impact of
      biologics and new treatment strategies on long term outcomes.

PMID- 25384807
TI  - Upper gastrointestinal bleeding associated with focal ulceration at the
      attachment base of a chronically retained endoscopic hemoclip.

PMID- 25384808
TI  - Severe colitis caused by biologics: what an endoscopist needs to know.

PMID- 25384810
TI  - Perspectives in primary care: implementing patient-centered care coordination for
      individuals with multiple chronic medical conditions.

PMID- 25384812
TI  - Frequency and prioritization of patient health risks from a structured health
      risk assessment.
AB  - PURPOSE: To describe the frequency and patient-reported readiness to change,
      desire to discuss, and perceived importance of 13 health risk factors in a
      diverse range of primary care practices. METHODS: Patients (n = 1,707) in 9
      primary care practices in the My Own Health Report (MOHR) trial reported general,
      behavioral, and psychosocial risk factors (body mass index [BMI], health status,
      diet, physical activity, sleep, drug use, stress, anxiety or worry, and
      depression). We classified responses as "at risk" or "healthy" for each factor,
      and patients indicated their readiness to change and/or desire to discuss
      identified risk factors with providers. Patients also selected 1 of the factors
      they were ready to change as most important. We then calculated frequencies
      within and across these factors and examined variation by patient characteristics
      and across practices. RESULTS: On average, patients had 5.8 (SD = 2.12; range, 0
      13) unhealthy behaviors and mental health risk factors. About 55% of patients had
      more than 6 risk factors. On average, patients wanted to change 1.2 and discuss
      0.7 risks. The most common risks were inadequate fruit/vegetable consumption
      (84.5%) and overweight/obesity (79.6%). Patients were most ready to change BMI
      (33.3%) and depression (30.7%), and most wanted to discuss depression (41.9%) and
      anxiety or worry (35.2%). Overall, patients rated health status as most
      important. CONCLUSIONS: Implementing routine comprehensive health risk
      assessments in primary care will likely identify a high number of behavioral and
      psychosocial health risks. By soliciting patient priorities, providers and
      patients can better manage counseling and behavior change.

PMID- 25384813
TI  - The cluster-randomized BRIGHT trial: Proactive case finding for community
      dwelling older adults.
AB  - PURPOSE: People are now living longer, but disability may affect the quality of
      those additional years of life. We undertook a trial to assess whether case
      finding reduces disability among older primary care patients. METHODS: We
      conducted a cluster-randomized trial of the Brief Risk Identification Geriatric
      Health Tool (BRIGHT) among 60 primary care practices in New Zealand, assigning
      them to an intervention or control group. Intervention practices sent a BRIGHT
      screening tool to older adults every birthday; those with a score of 3 or higher
      were referred to regional geriatric services for assessment and, if needed,
      service provision. Control practices provided usual care. Main outcomes, assessed
      in blinded fashion, were residential care placement and hospitalization, and
      secondary outcomes were disability, assessed with Nottingham Extended Activities
      of Daily Living Scale (NEADL), and quality of life, assessed with the World
      Health Organization Quality of Life scale, abbreviated version (WHOQOL-BREF).
      RESULTS: All 8,308 community-dwelling patients aged 75 years and older were
      approached; 3,893 (47%) participated, of whom 3,010 (77%) completed the trial.
      Their mean age was 80.3 (SD 4.5) years, and 55% were women. Overall, 88% of the
      intervention group returned a BRIGHT tool; 549 patients were referred. After 36
      months, patients in the intervention group were more likely than those in the
      control group to have been placed in residential care: 8.4% vs 6.2% (hazard ratio
      = 1.32; 95% CI, 1.04-1.68; P = .02). Intervention patients had smaller declines
      in mean scores for physical health-related quality of life (1.6 vs 2.9 points, P
      = .007) and psychological health-related quality of life (1.1 vs 2.4 points, P =
      .005). Hospitalization, disability, and use of services did not differ between
      groups, however. CONCLUSIONS: Our case-finding strategy was effective in
      increasing identification of older adults with disability, but there was little
      evidence of improved outcomes. Further research could trial stronger primary care
      integration strategies.

PMID- 25384814
TI  - Adoption, reach, implementation, and maintenance of a behavioral and mental
      health assessment in primary care.
AB  - PURPOSE: Guidelines recommend screening patients for unhealthy behaviors and
      mental health concerns. Health risk assessments can systematically identify
      patient needs and trigger care. This study seeks to evaluate whether primary care
      practices can routinely implement such assessments into routine care. METHODS: As
      part of a cluster-randomized pragmatic trial, 9 diverse primary care practices
      implemented My Own Health Report (MOHR)-an electronic or paper-based health
      behavior and mental health assessment and feedback system paired with counseling
      and goal setting. We observed how practices integrated MOHR into their workflows,
      what additional practice staff time it required, and what percentage of patients
      completed a MOHR assessment (Reach). RESULTS: Most practices approached (60%)
      agreed to adopt MOHR. How they implemented MOHR depended on practice resources,
      informatics capacity, and patient characteristics. Three practices mailed
      patients invitations to complete MOHR on the Web, 1 called patients and completed
      MOHR over the telephone, 1 had patients complete MOHR on paper in the office, and
      4 had staff help patients complete MOHR on the Web in the office. Overall, 3,591
      patients were approached and 1,782 completed MOHR (Reach = 49.6%). Reach varied
      by implementation strategy with higher reach when MOHR was completed by staff
      than by patients (71.2% vs 30.2%, P <.001). No practices were able to sustain the
      complete MOHR assessment without adaptations after study completion. Fielding
      MOHR increased staff and clinician time an average of 28 minutes per visit.
      CONCLUSIONS: Primary care practices can implement health behavior and mental
      health assessments, but counseling patients effectively requires effort.
      Practices will need more support to implement and sustain assessments.

PMID- 25384816
TI  - A retrospective analysis of the relationship between medical student debt and
      primary care practice in the United States.
AB  - PURPOSE: We undertook a study to reexamine the relationship between educational
      debt and primary care practice, accounting for the potentially confounding effect
      of medical student socioeconomic status. METHODS: We performed retrospective
      multivariate analyses of data from 136,232 physicians who graduated from
      allopathic US medical schools between 1988 and 2000, obtained from the American
      Association of Medical Colleges Graduate Questionnaire, the American Medical
      Association Physician Masterfile, and other sources. Need-based loans were used
      as markers for socioeconomic status of physicians' families of origin. We
      examined 2 outcomes: primary care practice and family medicine practice in 2010.
      RESULTS: Physicians who graduated from public schools were most likely to
      practice primary care and family medicine at graduating educational debt levels
      of $50,000 to $100,000 (2010 dollars; P <.01). This relationship between debt and
      primary care practice persisted when physicians from different socioeconomic
      status groups, as approximated by loan type, were examined separately. At higher
      debt, graduates' odds of practicing primary care or family medicine declined. In
      contrast, private school graduates were not less likely to practice primary care
      or family medicine as debt levels increased. CONCLUSIONS: High educational debt
      deters graduates of public medical schools from choosing primary care, but does
      not appear to influence private school graduates in the same way. Students from
      relatively lower income families are more strongly influenced by debt. Reducing
      debt of selected medical students may be effective in promoting a larger primary
      care physician workforce.

PMID- 25384815
TI  - Impact of continuity of care on mortality and health care costs: a nationwide
      cohort study in Korea.
AB  - PURPOSE: Continuity of care is considered a core element of high-quality primary
      care, but its impact on mortality and health care costs is unclear. We aimed to
      determine the impact of continuity of care on mortality, costs, and health
      outcomes in patients with newly diagnosed cardiovascular risk factors. METHODS:
      We conducted a cohort study of a 3% nationwide random sample of Korean National
      Health Insurance enrollees. A total of 47,433 patients who had received new
      diagnoses of hypertension, diabetes, hypercholesterolemia, or their complications
      in 2003 or 2004 were included. We determined standard indices of continuity of
      care-most frequent provider continuity (MFPC), modified, modified continuity
      index (MMCI), and continuity of care index (COC)-and evaluated their association
      with study outcomes over 5 years of follow-up. Outcome measures included overall
      mortality, cardiovascular mortality, incident cardiovascular events, and health
      care costs. RESULTS: The multivariable-adjusted hazard ratios (HRs) for all-cause
      mortality, cardiovascular mortality, incident myocardial infarction, and incident
      ischemic stroke comparing participants with COC index below the median to those
      above the median were HR = 1.12 (95% CI, 1.04-1.21), 1.30 (1.13-1.50), 1.57 (1.28
      1.95), and 1.44 (1.27-1.63), respectively. Similar findings were obtained for
      other indices of continuity of care. Lower continuity of care was also associated
      with increased inpatient and outpatient days and costs. CONCLUSIONS: Lower
      indices of continuity of care in patients with newly diagnosed hypertension,
      diabetes, and hypercholesterolemia were associated with higher all-cause and
      cardiovascular mortality, cardiovascular events, and health care costs. Health
      care systems should be designed to support long-term trusting relationships
      between patients and physicians.

PMID- 25384817
TI  - Two techniques to make swallowing pills easier.
AB  - To evaluate whether 2 techniques (the pop-bottle method for tablets and the lean
      forward technique for capsules) ease swallowing of tablets and capsules, we
      conducted a cross-sectional study including 151 adults of the general German
      population. Participants swallowed 16 differently shaped placebos, rated their
      ease of swallowing on an 8-point Likert scale, and swallowed the 2 dosage forms
      that they had rated most difficult again using the appropriate technique. The pop
      bottle method substantially improved swallowing of tablets in 59.7% (169/283) and
      the lean-forward technique for capsules in 88.6% (31/35). Both techniques were
      remarkably effective in participants with and without reported difficulties
      swallowing pills and should be recommended regularly.

PMID- 25384818
TI  - Patient-controlled taping for the treatment of ingrown toenails.
AB  - Various methods are used to treat ingrown or pincer-like toenails. We developed a
      novel taping method to prevent topical interruption of the circulation and
      resulting skin conditions and evaluated it over 14.5 years. We instructed 541
      patients or their guardians in the use of the technique. Ingrown toenail symptoms
      and abnormal nail growth were resolved and no additional therapy was required in
      276 patients. The novel taping method was significantly more effective than
      treatments our patients had received previously. Patient-controlled taping is the
      first-line treatment for every ingrown or curved toenail seen in our clinic.

PMID- 25384819
TI  - Hospitalized women's willingness to pay for an inpatient screening mammogram.
AB  - Lower rates for breast cancer screening persist among low income and uninsured
      women. Although Medicare and many other insurance plans would pay for screening
      mammograms done during hospital stays, breast cancer screening has not been part
      of usual hospital care. This study explores the mean amount of money that
      hospitalized women were willing to contribute towards the cost of a screening
      mammogram. Of the 193 enrolled patients, 72% were willing to pay a mean of $83.41
      (95% CI, $71.51-$95.31) in advance towards inpatient screening mammogram costs.
      The study's findings suggest that hospitalized women value the prospect of
      screening mammography during the hospitalization. It may be wise policy to offer
      mammograms to nonadherent hospitalized women, especially those who are at high
      risk for developing breast cancer.

PMID- 25384820
TI  - Validation of 2 new measures of continuity of care based on year-to-year follow
      up with known providers of health care.
AB  - PURPOSE: In a primary care context favoring group practices, we assessed the
      validity of 2 new continuity measures (both versions of known provider
      continuity, KPC) that capture the concentration of care over time from multiple
      physicians (multiple provider continuity, KPC-MP) or from the physician seen most
      often (personal provider continuity, KPC-PP). METHODS: Patients with diabetes or
      cardiovascular disease (N = 765) were approached in the waiting rooms of 28
      primary care clinics in 3 regions of the province of Quebec, Canada; answered a
      survey questionnaire measuring relational continuity, interpersonal
      communication, coordination within the clinic, coordination with specialists, and
      overall coordination; and gave permission for their medical records to be
      reviewed and their medical services utilization data for the previous 2 years to
      be accessed to measure KPC. Using generalized linear mixed models, we assessed
      the association between KPC and the patients' responses. RESULTS: Among the 5
      different patient-reported measures or their combination, KPC-MP was
      significantly related with overall coordination of care: for high continuity, the
      odds ratio (OR) = 2.02 (95% CI, 1.33-3.07), and for moderate continuity, OR =
      1.61 (95% CI, 1.06-2.46). KPC-MP was also related with the combined continuity
      score: for high continuity, OR = 1.52 (95% CI, 1.11-2.09), and for moderate
      continuity, OR = 1.48 (95% CI, 1.10-2.00). KPC-PP was not significantly
      associated with any of the survey measures. CONCLUSIONS: The KPC-MP measure,
      based on readily available administrative data, is associated with patient
      perceived overall coordination of care among multiple physicians. KPC measures
      are potentially a valuable and low-cost way to follow the effects of changes
      favoring group practice on continuity of care for entire populations. They are
      easy to replicate over time and across jurisdictions.

PMID- 25384821
TI  - Health information technology: an untapped resource to help keep patients
      insured.
AB  - The recent confluence of: (1) changing state and national insurance-related
      policies, and (2) the rapid growth in electronic health record (EHR) use, yields
      an unprecedented opportunity for patient-centered medical homes (PCMHs) and other
      primary care practices or care settings to use health information technology
      (HIT) and health information exchange (HIE) in novel ways to impact patient
      health. We propose that HIT is an untapped resource for supporting clinic-based
      efforts to help eligible patients obtain and maintain insurance coverage. This
      commentary presents a conceptual model and guiding principles for this idea.
      Additionally, it describes insurance support tools that could be used to conduct
      'inreach' and 'outreach' with patients around health insurance, similar to how
      HIT is used to manage chronic disease and panels of patients, and to improve
      population health outcomes.

PMID- 25384823
TI  - Reducing hospital admissions: small primary care practices shine in national
      study.

PMID- 25384822
TI  - From triple to quadruple aim: care of the patient requires care of the provider.
AB  - The Triple Aim-enhancing patient experience, improving population health, and
      reducing costs-is widely accepted as a compass to optimize health system
      performance. Yet physicians and other members of the health care workforce report
      widespread burnout and dissatisfaction. Burnout is associated with lower patient
      satisfaction, reduced health outcomes, and it may increase costs. Burnout thus
      imperils the Triple Aim. This article recommends that the Triple Aim be expanded
      to a Quadruple Aim, adding the goal of improving the work life of health care
      providers, including clinicians and staff.

PMID- 25384824
TI  - Pisacano Leadership Foundation names 2014 Pisacano Scholars.

PMID- 25384826
TI  - Electronic health records: how will students learn if they can't practice?

PMID- 25384827
TI  - Transforming a toolbox into a treasure chest.

PMID- 25384829
TI  - AHRQ updates on primary care research: the AHRQ Patient-Centered Medical Home
      Resource Center.

PMID- 25384831
TI  - Evidence-based approach to improving immunity to manage cattle health.
AB  - Bovine respiratory disease (BRD) involves interactions between respiratory
      pathogens and stressors. Marketing beef cattle in North America frequently
      involves commingling of cattle from different backgrounds along with various
      stressors. Veterinarians are faced with unique challenges when designing
      preventive health care protocols. Research at Oklahoma State University has
      generated information to assist the practitioner to make more informed
      recommendations regarding the value of a single vaccination or revaccination in
      high-risk cattle, and the benefits of management programs at the farm or ranch of
      origins, particularly in regard to the impact of commingling of cattle from
      different origins. 

PMID- 25384832
TI  - A comprehensive study of myocardial redox homeostasis in naturally and
      mimetically aged rats.
AB  - Age-related myocardial dysfunction has important implications with impaired redox
      homeostasis. Current study focused on investigation of redox homeostasis and
      histopathological changes in the myocardium of mimetically (MA), naturally aged
      (NA), and young control (YC) rats. Chronic D-galactose administration to young
      male Wistar rats (5 months old) was used to set up experimental aging models. We
      investigated 16 different oxidative damage biomarkers which have evaluated redox
      homeostasis of cellular macromolecules such as protein, lipid, and DNA. As a
      protein oxidation biomarker, advanced oxidation end products, protein carbonyl
      groups, protein-bound advanced glycation end products, dityrosine, kynurenine,
      and N-formylkynurenine concentrations in MA and NA rats were found to be
      significantly higher compared to those in YC rats. On the other hand, the levels
      of protein thiol groups were not significantly different between groups, whereas
      lipid peroxidation biomarkers such as conjugated diens, lipid hydroperoxides, and
      malondialdehyde in MA and NA rats were found to be significantly higher in
      comparison to those in YCs. For the assessment of oxidative DNA damage, we
      analyzed eight hydroxy-5'-deoxyguanosine concentrations of MA and NA groups which
      were higher than YCs. As an antioxidant status in the MA and NA groups, Cu-Zn
      superoxide dismutase, ferric reducing antioxidant power, and total thiol levels
      were lower than those in the YCs. Only nonprotein thiol levels were not
      significantly different. We also observed similar histopathological changes in MA
      and NA rats. We concluded that the mimetic aging model could be considered as a
      reliable experimental model for myocardial senescence. 

PMID- 25384833
TI  - Image-based motion correction for optical mapping of cardiac electrical activity.
AB  - Optical mapping, with membrane-bound, voltage-sensitive dyes, is widely used for
      in vitro recording of cardiac electrical activity. The spatial registration of
      such maps is lost when the heart moves with respect to a fixed photodetector
      array and contraction can generate substantial artifact if background
      fluorescence is not uniformly distributed. While motion artifact is commonly
      suppressed with electromechanical uncoupling agents, there are circumstances
      where these are undesirable. This study outlines a novel image-based approach for
      retrospective motion artifact correction. Isolated Langendorff-supported rat
      hearts (n = 8), stained with di-4-ANEPPS, were illuminated at 516 +/- 14 nm and
      fluorescent emission (>565 +/- 10 nm) was acquired with a charge multiplying CCD
      camera. Background fluorescence was segmented in successive frames and stabilized
      using a non-rigid image registration algorithm. The resultant image deformation
      was used to estimate material point movement on the heart surface, so that total
      fluorescence could be mapped frame-by-frame to appropriate reference pixels.
      Finally, residual motion artifact was identified and removed. The effectiveness
      of this correction method was evaluated over 18 experimental datasets. Signal-to
      noise ratio was increased more than fourfold, and activation time and action
      potential duration (APD) could be estimated at 24% more pixels than in the raw
      data. The variability of all APD measures was substantially reduced (i.e. APD50
      estimated as 83.8 +/- 45.8 ms before correction was 52.1 +/- 4.7 ms afterward).
      This approach provides a robust means of recovering optical action potentials in
      the presence of substantial motion artifact. 

PMID- 25384834
TI  - Duration of TGF-beta3 Exposure Impacts the Chondrogenic Maturation of Human MSCs
      in Photocrosslinked Carboxymethylcellulose Hydrogels.
AB  - Intervertebral disc (IVD) herniation can be caused by both degeneration and
      traumatic injury, ultimately resulting in back pain or sciatica due to disc
      protrusion. Replacement of the nucleus pulposus (NP) tissue during surgical
      intervention post herniation could improve the long-term stability of the
      functional spinal unit. Tissue engineering strategies may potentially restore
      both biological and mechanical function of the NP. Recently, photocrosslinked
      carboxymethylcellulose (CMC) hydrogels were shown to support chondrogenic, NP
      like extracellular matrix (ECM) elaboration by human mesenchymal stromal cells
      (hMSCs) when supplemented with TGF-beta3. However, long-term preconditioning with
      soluble growth factors in vitro or the use of sustained growth factor delivery
      vehicles in vivo can be expensive and difficult to control. Transient
      supplementation with growth factors has been shown to maintain or improve
      maturation of tissue-engineered constructs. The objective of this study was to
      evaluate the influence of TGF-beta3 exposure time on hydrogel bulk properties and
      NP-like matrix elaboration in hMSC-laden CMC hydrogels. Constructs were exposed
      to TGF-beta3 for 2 weeks (Transient), 8 weeks (Continuous) or 0 weeks (controls).
      After 8 weeks of culture, both the Transient and Continuous groups exhibited
      increased ECM accumulation compared to 2 weeks and controls. The Transient group
      displayed significantly greater accumulation of collagens I and II, while GAG
      content was significantly higher in the Continuous group by 8 weeks. Distribution
      of ECM was more homogeneous in the Continuous group, while the Transient group
      exhibited more concentrated accumulation in the periphery of the hydrogel by 8
      weeks. Mechanical properties improved over time in both groups, however,
      Continuous constructs demonstrated significantly more robust mechanical
      properties (equilibrium modulus and peak stress) compared to Transient gels at 8
      weeks. Although the functional properties of Transient constructs did not surpass
      those achieved by Continuous scaffolds, they increased and were maintained upon
      growth factor removal at 2 weeks, and were greater than controls. Additionally,
      Transient construct mechanical properties (equilibrium modulus, % relaxation)
      were similar to those of native NP tissue. The differences seen in ECM
      distribution and subsequent construct functional maturation are likely due to the
      time available for diffusion of growth factors through the construct. Overall,
      these findings support the use of short-term TGF-beta3 treatment to promote
      sufficient long-term tissue maturation in vitro in this hMSC-laden CMC hydrogel
      system. 

PMID- 25384835
TI  - Influence of the calcaneus shape on the risk of posterior heel ulcer using 3D
      patient-specific biomechanical modeling.
AB  - Most posterior heel ulcers are the consequence of inactivity and prolonged time
      lying down on the back. They appear when pressures applied on the heel create
      high internal strains and the soft tissues are compressed by the calcaneus. It is
      therefore important to monitor those strains to prevent heel pressure ulcers.
      Using a biomechanical lower leg model, we propose to estimate the influence of
      the patient-specific calcaneus shape on the strains within the foot and to
      determine if the risk of pressure ulceration is related to the variability of
      this shape. The biomechanical model is discretized using a 3D Finite Element mesh
      representing the soft tissues, separated into four domains implementing Neo
      Hookean materials with different elasticities: skin, fat, Achilles' tendon, and
      muscles. Bones are modelled as rigid bodies attached to the tissues. Simulations
      show that the shape of the calcaneus has an influence on the formation of
      pressure ulcers with a mean variation of the maximum strain over 6.0 percentage
      points over 18 distinct morphologies. Furthermore, the models confirm the
      influence of the cushion on which the leg is resting: a softer cushion leading to
      lower strains, it has less chances of creating a pressure ulcer. The methodology
      used for patient-specific strain estimation could be used for the prevention of
      heel ulcer when coupled with a pressure sensor. 

PMID- 25384836
TI  - Is mechanical bowel preparation still necessary for gynecologic laparoscopic
      surgery? A meta-analysis.
AB  - INTRODUCTION: A number of studies have proven that mechanical bowel preparation
      (MBP) has no benefits in elective colorectal surgery. However, studies
      specifically related to gynecologic laparoscopic surgery are scant. We undertook
      a meta-analysis to assess the necessity of MBP before gynecologic laparoscopic
      surgery. METHODS: The electronic databases MEDLINE, EMBASE, and the Cochrane
      Central Register of Controlled Trials were systematically searched to identify
      relevant randomized controlled trials. Two authors independently extracted data
      from each study. The primary outcome of interest was the quality of surgical
      field. Secondary outcomes of interest included postoperative pain, abdominal
      swelling, nausea/vomiting, and length of hospital stay. RESULTS: Three studies
      involving 372 participants were included in the meta-analysis. The results showed
      that MBP did not significantly increase the overall quality of surgical field
      exposure (odds ratio, 0.82; 95% confidence interval [CI], 0.46-1.49; P = 0.52).
      MBP also did not appear to significantly change the mean scores of postoperative
      pain (weighted mean difference, 0.09; 95%CI, -0.54-0.71; P = 0.79), the incidence
      of nausea/vomiting (odds ratio, 1.56; 95%CI, 0.80 to 3.03; P = 0.19), the mean
      scores of abdominal swelling (weighted mean difference, -0.26; 95%CI, -0.83-0.30;
      P = 0.36), and length of hospital stay (weighted mean difference, 0.05; 95%CI, 
      0.13-0.22; P = 0.62). CONCLUSIONS: Our results suggest that routine use of MBP
      for gynecologic laparoscopic surgery should not be recommended. However,
      additional randomized controlled trials using large samples are needed to confirm
      these findings.

PMID- 25384837
TI  - Young Investigators Meeting 2014 Uta Eberlein, YIM'14 Award Winner.

PMID- 25384838
TI  - Amphotericin B-loaded polymeric nanoparticles: formulation optimization by
      factorial design.
AB  - In this study, PLGA or PLGA-PEG blend nanoparticles were developed loading
      amphotericin B (AmB), an antifungal agent broadly used in therapy. A 2(2) * 3(1)
      factorial experimental design was conducted to indicate an optimal formulation of
      nanoparticles containing AmB and demonstrate the influence of the interactions of
      components on the mean particle size and drug encapsulation efficiency. The
      independent variables analyzed were polymer amount (two levels) and organic phase
      (three factors in one level). The parameters methanol as cosolvent and higher
      polymer amount originated from the higher AmB encapsulation, but with the larger
      particle size. The selected optimized parameters were set as the lower polymer
      amount and ethyl acetate as cosolvent in organic phase, for both PLGA and PLGA
      PEG nanoparticles. These parameters originated from nanoparticles with the size
      of 189.5 +/- 90 nm and 169 +/- 6.9 nm and AmB encapsulation efficiency of 94.0 +/
      1.3% and 92.8 +/- 2.9% for PLGA and PLGA-PEG nanoparticles, respectively.
      Additionally, these formulations showed a narrow size distribution indicating
      homogeneity in the particle size. PLGA and PLGA-PEG nanoparticles are potential
      carrier for AmB delivery and the factorial design presented an important tool in
      optimizing nanoparticles formulations. 

PMID- 25384839
TI  - Development of coated blade spray ionization mass spectrometry for the
      quantitation of target analytes present in complex matrices.
AB  - Coated blade spray (CBS) is a technology based on solid-phase microextraction
      (SPME) that has been designed for the quick extraction/cleanup of analytes from
      complex matrices and direct desorption/ionization under ambient mass spectrometry
      conditions. The entire analytical process can be completed in less than 3 min and
      enables limits of quantitation in the low picogram-per-milliliter region to be
      reached. 

PMID- 25384840
TI  - Role of telaprevir plasma levels for predicting response to antiviral therapy in
      patients with hepatitis C virus genotype 1 infection.
AB  - OBJECTIVE: Telaprevir (TVR)-based triple therapy has substantially improved cure
      rates of hepatitis C virus (HCV) genotype 1 infection but side effects are
      frequent and often severe. Therefore, response predictors are needed for early
      identification of patients not responding to TVR-based triple therapy. MATERIAL
      AND METHODS: Forty-five patients (mean age: 54 +/- 13 years; male gender: 60%;
      treatment-experienced: 82%; cirrhosis: 58%) with HCV genotype 1 infection were
      treated with a TVR-based triple-therapy regimen. TVR plasma levels were analyzed
      by liquid chromatography electrospray-ionization-tandem mass spectrometry at
      weeks 2, 4, 8, and 12 of antiviral therapy. On-treatment HCV RNA response was
      assessed at weeks 4, 12, and 24 by real-time polymerase chain reaction. RESULTS:
      An extended rapid virological response (eRVR) and sustained virological response
      (SVR) was achieved in 21 of 45 patients (47%) and 36 of 45 (80%) patients,
      respectively. Mean +/- standard deviation TVR plasma levels at week 2 were 3.4 +/
      0.2 log10 ng/ml and did not differ over time (when assessed at weeks 4, 8, and
      12). TVR plasma levels at week 2 were significantly higher in patients who
      achieved an eRVR compared to those who did not achieve eRVR (3.5 +/- 0.1 vs. 3.3
      +/- 0.2 log10 ng/ml; p = 0.003) but were neither associated with SVR nor with
      treatment-related anemia. CONCLUSION: TVR plasma levels are associated with on
      treatment response but not with overall treatment efficacy. Given the high
      overall response rates to TVR-based triple therapy, our data suggest that TVR
      trough levels may not be a useful predictor of treatment response, and routine
      drug-level monitoring is not required.

PMID- 25384842
TI  - The attribution of success when using navigation aids.
AB  - Attitudes towards geographic information technology is a seldom explored research
      area that can be explained with reference to established theories of attribution.
      This article reports on a study of how the attribution of success and failure in
      pedestrian navigation varies with level of automation, degree of success and
      locus of control. A total of 113 participants took part in a survey exploring
      reflections on personal experiences and vignettes describing fictional navigation
      experiences. A complex relationship was discovered in which success tends to be
      attributed to skill and failure to the navigation aid when participants describe
      their own experiences. A reversed pattern of results was found when discussing
      the navigation of others. It was also found that navigation success and failure
      are associated with personal skill to a greater extent when using paper maps, as
      compared with web-based routing engines or satellite navigation systems.
      PRACTITIONER SUMMARY: This article explores the influences on the attribution of
      success and failure when using navigation aids. A survey was performed exploring
      interpretations of navigation experiences. Level of success, self or other as
      navigator and type of navigation aid used are all found to influence the
      attribution of outcomes to internal or external factors.

PMID- 25384843
TI  - Analysis of menisci formed on cones for single field of view parasite egg
      microscopy.
AB  - Parasite ova caused to accumulate in a single microscopic field simplifies
      monitoring soil-transmitted helminthiasis by optical microscopy. Here we
      demonstrate new egg-accumulating geometries based on annular menisci formed on
      the surface of a wetted cone. Fluidic features extracted from profile images of
      the system provided mathematical representations of the meniscus gradient that
      were compared quantitatively to numerical solutions of an axisymmetric Young
      Laplace equation. Our results show that the governing dynamics of these systems
      is dominated by the surface tension of the fluid. These image analysis and
      mathematical tools provide simple quantitative methods for system analysis and
      optimization. 

PMID- 25384844
TI  - Seeing is believing: novel imaging techniques help clarify microbial nanowire
      structure and function.
AB  - Novel imaging approaches have recently helped to clarify the properties of
      'microbial nanowires'. Geobacter sulfurreducens pili are actual wires. They
      possess metallic-like conductivity, which can be attributed to overlapping pi-pi
      orbitals of key aromatic amino acids. Electrostatic force microscopy recently
      confirmed charge propagation along the pili, in a manner similar to carbon
      nanotubes. The pili are essential for long-range electron transport to insoluble
      electron acceptors and interspecies electron transfer. Previous claims that
      Shewanella oneidensis also produce conductive pili have recently been recanted,
      based on novel live-imaging studies. The putative pili are, in fact, long
      extensions of the cytochrome-rich outer membrane and periplasm that, when dried,
      collapse to form filaments with dimensions similar to pili. It has yet to be
      demonstrated whether the cytochrome-to-cytochrome electron hopping documented in
      the dried membrane extensions takes place in intact hydrated membrane extensions
      or whether the membrane extensions enhance electron transport to insoluble
      electron acceptors such as Fe(III) oxides or electrodes. These findings
      demonstrate that G. sulfurreducens conductive pili and the outer membrane
      extensions of S. oneidensis are fundamentally different in composition, mechanism
      of electron transport and physiological role. New methods for evaluating filament
      conductivity will facilitate screening the microbial world for nanowires and
      elucidating their function.

PMID- 25384845
TI  - Perceptions of trophectoderm as a sentinel for embryo selection.

PMID- 25384846
TI  - Percutaneous paravalvular leak closure for symptomatic aortic regurgitation after
      CoreValve transcatheter aortic valve implantation.
AB  - OBJECTIVES: We present a case series of five patients in whom percutaneous
      paravalvular leak closure with the AVP4 device has been undertaken for
      symptomatic aortic regurgitation after CoreValve TAVI. BACKGROUND: Significant
      post-procedure aortic regurgitation (AR) is often difficult to assess, and is an
      important predictor of adverse outcome following TAVI. Paravalvular leak closure
      is an established procedure for surgical aortic prostheses, and has been
      undertaken for Edwards TAVIs, but has not been described for closure of CoreValve
      paravalvular leaks. METHODS AND RESULTS: Five patients were treated (mean age 81
      +/- 4 years) with residual grade 3-4 AR following placement of a single CoreValve
      (n = 2), double CoreValve (n = 2) or CoreValve within a bioprosthetic AVR (n =
      1). The mean time post TAVI implantation was 308 +/- 269 days. All patients were
      symptomatic with persistent NYHA Grade III dyspnoea. 6 devices were deployed
      successfully, with mean procedure time of 109 +/- 23 min. There were no
      procedural complications and all patients were discharged home by Day 2. Residual
      AR after treatment was grade 0 (n = 2), grade 1 (n = 1), grade 2 (n = 1) and
      grade 3 (n = 1). Symptomatic improvement was noted in all 4 patients who have
      been reviewed in clinic since. CONCLUSIONS: This small series demonstrates the
      feasibility of paravalvular leak closure with the CoreValve TAVI, despite the
      adverse aortic lattice. The AVP4 device is ideally suited to this situation as it
      will pass through a 0.038' lumen and can therefore be delivered down standard
      diagnostic catheters.

PMID- 25384847
TI  - Traditional Chinese medication for cardiovascular disease.
AB  - Traditional Chinese medication (TCM) is increasingly used to treat cardiovascular
      disease (CVD) in China and some other Asian countries. However, therapeutic
      efficacy and adverse effects of TCM are difficult to evaluate because few large
      scale, randomized controlled trials (RCTs) enrolling patients with CVD have been
      performed. In this Review, we critically examine the current evidence on the
      cardiovascular effects of TCM. We reviewed 68 RCTs that included a total of
      16,171 patients. The methodological quality of the trials was generally low. Only
      three reports described adverse cardiovascular events specifically, although in
      most studies TCM was associated with significant improvements in surrogate end
      points for hypertension, coronary heart disease, cardiac arrhythmias, and heart
      failure. The risk of adverse effects was not increased compared with no
      intervention, placebo, or Western medications. However, whether TCM is effective
      in reducing the all-cause or cardiovascular mortality in patients with CVD
      remains unknown and must be tested in large-scale RCTs with adverse
      cardiovascular events as primary end points. 

PMID- 25384848
TI  - The Kuroshio current influences genetic diversity and population genetic
      structure of a tropical seagrass, Enhalus acoroides.
AB  - Information on genetic diversity and differentiation of seagrass populations is
      essential for the conservation of coastal ecosystems. However, little is known
      about the seagrasses in the Indo-West Pacific Ocean, where the world's highest
      diversity of seagrasses occurs. The influence of sea currents on these
      populations is also unknown. We estimated the genetic diversity and population
      genetic structure and identified reproductive features in Enhalus acoroides
      populations from the Yaeyama Islands, Hainan Island and the Philippines. The
      Philippines are situated at the centre of the E. acoroides range, Yaeyama and
      Hainan are peripheral populations, and the Yaeyama population is at the northern
      limit of the species range. The powerful Kuroshio Current flows from the
      Philippines to Yaeyama. Genetic analyses using nine microsatellite markers
      indicated that reproduction of E. acoroides is mostly sexual. Clonal diversity
      does not decrease in northern populations, although genetic diversity does.
      However, the genetic diversity of the Yaeyama populations is greater than that of
      the Hainan populations. Significant genetic differentiation among most
      populations was evident; however, the Yaeyama and north-east Philippines
      populations were genetically similar, despite being separated by ~1100 km. An
      assignment test suggested that recruitment occurs from the north-east Philippines
      to Yaeyama. The strong current in this region is probably responsible for the
      extant genetic diversity and recruitment patterns.

PMID- 25384849
TI  - Peri-operative cerebrospinal fluid leak during single-stage bone-anchored hearing
      aid implantation: case report.
AB  - BACKGROUND: A bone-anchored hearing aid uses the principle of bone conduction and
      osseointegration to transfer sound vibrations to a functioning inner ear. It
      consists of a permanent titanium implant, and removable abutment and sound
      processor. Informed consent requires discussion of the procedural benefits,
      alternatives and complications. The risks of bone-anchored hearing aid surgery
      include infection, soft tissue hypertrophy, skin graft or flap failure,
      osseointegration failure, and the need for further surgery. CASE REPORT: A case
      of cerebrospinal fluid leak in a patient undergoing bone-anchored hearing aid
      surgery is reported and discussed. CONCLUSION: Bone-anchored hearing aid surgery
      poses a risk of breaching the inner table of the temporal bone and dura,
      resulting in a cerebrospinal fluid leak; the risk of meningitis is rare but
      serious. The surgeon should discuss the possibility of cerebrospinal fluid leak
      when consenting patients. Pre-operative computerised tomography scanning should
      be considered in certain individuals to aid implant placement.

PMID- 25384850
TI  - Development of a real-time PCR for Escherichia coli based on gadE, an acid
      response regulatory gene.
AB  - Increasingly, molecular methods have become important in identification and
      confirmation of bacteria at the species level. Rapid molecular methods provide
      sensitivity and specificity while reducing cost and resources. The primary goal
      of this study was to develop a real-time PCR assay for identification of
      Escherichia coli from an agar plate. GadE (gadE) directly regulates the glutamate
      dependent acid response system (GDAR) in E. coli and is responsible for survival
      of at pH 2. Based on gene sequence data, a real-time PCR assay targeting gadE was
      developed for this purpose. Seventy bacterial isolates recovered from ground beef
      enrichments and 714 isolates from caecal contents were identified biochemically
      and tested with the real-time PCR assay developed in this study. The PCR assay
      and the biochemical identification had 100% agreement on the tested isolates. The
      gadE real-time PCR assay was demonstrated in this study to be an inexpensive,
      reliable method for confirming E. coli colonies within 1.5 h from an agar plate,
      thereby saving on final identification time.

PMID- 25384851
TI  - Randomization, matching, and propensity scores in the design and analysis of
      experimental studies with measured baseline covariates.
AB  - In many experimental situations, researchers have information on a number of
      covariates prior to randomization. This information can be used to balance
      treatment assignment with respect to these covariates as well as in the analysis
      of the outcome data. In this paper, we investigate the use of propensity scores
      in both of these roles. We also introduce a randomization procedure in which the
      balance of all measured covariates is approximately indexed by the variance of
      the empirical propensity scores and randomization is restricted to those
      permutations with the least variable propensity scores. This procedure is
      compared with recently proposed methods in terms of resulting covariate balance
      and estimation efficiency. Properties of the estimators resulting from each
      procedure are compared with estimates which incorporate the propensity score in
      the analysis stage. Simulation results show that analytical adjustment for the
      propensity score yields results on par with those obtained through restricted
      randomization procedures and can be used in conjunction with such procedures to
      further improve inferential efficiency.

PMID- 25384852
TI  - [Diagnostics and therapy of chronic stable coronary artery disease : new
      guidelines of the European Society of Cardiology].
AB  - The European Society of Cardiology (ESC) guidelines on the management of stable
      coronary artery disease published in 2013 give practical recommendations for
      diagnostics and therapy. The approach depends on the clinical picture and
      symptoms of the patient, the severity and extent of ischemia, the degree and
      location of coronary stenoses, additional cardiac findings and finally on non
      cardiac comorbidities. The selection of suitable diagnostic tools is based on the
      tabulated pretest probability for the presence of coronary artery disease which
      plays an important and central role in the diagnostic algorithm. An invasive
      approach is recommended only in patients with severe angina, i.e. a Canadian
      Cardiovascular Society (CCS) angina grading scale of >= CCS3 or in patients who
      are at high risk for death or myocardial infarction based on the results of the
      test used for detection of ischemia. Detailed therapeutic recommendations are
      given for medicinal and interventional or surgical therapy. Medicinal therapy
      includes drugs both for relief of symptoms and prevention of cardiovascular
      events. Recommendations are also given for the use of new antianginal drugs. A
      PCI is only indicated in vessels causing ischemia which can be verified by using
      fractional flow reserve measurements. The indications for PCI now also include
      patients with a low SYNTAX score and multivessel disease or left main stenosis;
      however, the optimal strategy should be individually determined in heart team
      discussions. 

PMID- 25384854
TI  - Human freedom and the brain.
AB  - Freedom of will does exist, it is self-leadership of man based on reason and
      ethos. Evidence comes from truth. Determinism cannot be proved since if you try,
      you mean to prove a truth; but there is no truth without freedom. By contrast for
      freedom there are many pieces of evidence e.g. science, arts, technology. Freedom
      utilizes creative abstract thinking with phantasy. Freedom is graded, limited,
      based on nature, but not developed without good will. We perceive reliably
      freedom by self-consciousness and in other persons as long as we are sober.
      Freedom needs intelligence, but is more, it is a creative and moral virtue. The
      basis for freedom is phylogenesis and culture, in the individual learning and
      experimenting. Factors in the becoming of freedom are not only genes and
      environment but also self-discipline. But the creativity of free will is
      dangerous. Man therefore needs morale. Drives and feelings become humanized,
      cultural interests are developed. There is a humane nobility from long good will.

PMID- 25384853
TI  - [New ESH/ESC guidelines on arterial hypertension : what is new and what
      indications remain for renal denervation?].
AB  - Arterial hypertension is one of the most common diseases in the western world and
      one of the most important risk factors for other cardiovascular diseases. Despite
      widespread therapeutic options, there is still a large proportion of patients
      with uncontrolled hypertension. The new European guidelines on hypertension give
      clear lines of action for diagnosis and treatment sorted into appropriate
      evidence levels based on current scientific data. Such evidence is still unclear
      for renal denervation so that no clear recommendations can be given. 

PMID- 25384855
TI  - Neurobiological underpinnings of personality disorders.

PMID- 25384856
TI  - Causes, diagnoses and treatment of post-traumatic stress disorder.

PMID- 25384857
TI  - Anxiety disorders: causes, diagnosis and treatment.

PMID- 25384858
TI  - On psychodynamics of personal value-judgements - Nietzsche's theory of resentment
      and its reception by Karl Jaspers and Kurt Schneider.
AB  - A hundred years ago when Karl Jaspers was introducing psychological understanding
      to psychiatry the founder of the school of Heidelberg spoke of Friedrich
      Nietzsche as one of the "greatest" psychologists. Especially his theory of
      resentment with its core thesis unconscious prejudices were influencing our
      behaviour was able to illuminate the complex structure of human will. Taking into
      account this horizon of psychiatric history of ideas the presentation wants to
      persecute the following three questions: 1) Why the postulate which Nietzsche was
      giving on cultural prejudices of our thoughts, feelings and acts was so
      provocative so that many of the classical thinkers of psychological understanding
      were taking it up according to the needs of their disciplines sociology,
      psychology, psychiatry and philosophy? 2) What were the results of this inspiring
      theory which could be especially seen in the works of Karl Jaspers and Kurt
      Schneider? In other words: What were the aspects in which they agreed in their
      reception of Nietzsche and what were the points in which the two psychiatrists of
      the school of Heidelberg differed in the way they took the theory of resentment
      into account for their psychological understanding? 3) What could be the actual
      significance of the historical fact that Nietzsche and in his footsteps Max Weber
      were taking deep influence on psychiatric thinking around 1900? 

PMID- 25384859
TI  - The role of diagnosis in psychiatric forensic examination.

PMID- 25384860
TI  - Immunopathogenesis of multiple sclerosis.
AB  - Immunopathogenesis of multiple sclerosis is a complex process involving T cell
      mediated autoimmunity at initial stage of disease. A long standing view that Th1
      cells are critical for early inflammatory development of lesions is challenging
      by recent findings that Th1 helper cells with Th17 phenotype are even more
      important. A complex autoimmunity of MS is further complicated with evidence that
      CD8 cells, regulatory T cells, clonal expansion of B cells, cells of myelin
      lineage, antibodies and complement, as well as process intrinsic to central
      nervous system contribute to the tissue destruction. Although there are a lot of
      evidences about inflammatory phase of MS, far less is known about mechanisms
      involved in degenerative phase of disease. It is not known weather quantitative,
      or qualitative differences in inflammatory response contributes to destruction of
      the tissue, or as it was shown experimentally demyelination may sometimes occur
      independent of T cells. Understanding of immunopathogenesis of MS especially
      regarding various stages of disease is necessary for clinicians in choosing
      optimal therapy of MS in individual patients. Influences of immunomodulatory
      treatment on various stages of MS immuno-pathogenesis are presented. 

PMID- 25384861
TI  - Importance of neurophysiological investigations in the diagnosis of multiple
      sclerosis.

PMID- 25384862
TI  - Clinical and neurochemical characteristics of pediatric multiple sclerosis - CSF
      analysis as knowledge base for differential diagnosis and pathophysiology.
AB  - Multiple sclerosis (MS) is the most common chronic inflammatory disease of the
      central nervous system affecting young adults. Although adults and children share
      important features of the disease, they also differ in some clinical,
      radiological and laboratory aspects. This review focuses on the
      neuroimmunological findings in the cerebrospinal fluid of children with MS
      pointing out that there is already at earliest time of clinical manifestation a
      neuroimmunological pattern, which differs only in intensity of the humoral immune
      response but not in frequency and does not support a neuroimmunological
      difference between early onset from adult onset MS. The humoral immune response
      with intrathecal IgG and IgM class response and the polyspecific production of
      antibodies against a wide range of antigens (MRZ antibody response) further helps
      to differentiate childhood MS from ADEM as the main differential diagnostic
      challenge. 

PMID- 25384863
TI  - Urogenital dysfunction in patients with multiple sclerosis.
AB  - The occurrence of urogenital dysfunction as an isolated early symptom in multiple
      sclerosis (MS) is rare, but the prevalence thereof becomes high with progression
      of disease. Lower urinary tract dysfunction may add to the cause of death
      (particularly through urinary infections), but both urinary and sexual
      dysfunction significantly affect quality of life of patients. Both storage and
      evacuation of urine may be affected by MS, and ultimatively the functional
      diagnosis can only be made by urodynamic testing. As upper urinary tract
      affection is, however, rare (and can be prevented by timely ultrasound imaging),
      a first stage diagnostics in the MS center by the neurologist and specialized
      nurse is appropriate. History, urine tests and post void residual urine
      determination (preferably by ultrasound) should provide necessary data for
      treatment of infections, and also symptomatic management of frequency, urgency
      and incontinence by bladder training, anticholinergics, and intermittent self
      catheterization (as indicated); the referral to urologist may be reserved for
      patients who fail first line treatment. Treatment in the late stages of MS is as
      yet little researched, but eventually a suprapubic catheter is the preferred
      method of bladder emptying. Sexual dysfunction should be actively sought in MS
      patients (in men erectile and ejaculation dysfunction, in women deficient
      lubrication and genital hyper- or hyposensitivity are frequent). Clinical
      examination contributes little to clarification of neurogenic sexual dysfunction,
      but defines the extent of other deficits due to MS, which may be relevant for
      sexual counseling (spasticity, sensory loss). Sildenafil has been demonstrated to
      be effective in treatment of men, but not in women. Other management options
      exist, and the doctor and nurse in the MS center should be proactive in providing
      first line counseling and management. 

PMID- 25384864
TI  - Immunotherapy of multiple sclerosis.
AB  - Multiple sclerosis (MS) is regarded as a prototypic inflammatory autoimmune
      central nervous system disorder causing neurological disability in young adults.
      Recommended basic immunomodulatory therapies of MS are currently interferon beta
      and glatiramer acetate. Both have proven to be clinically and paraclinically
      effective and clinical evidence suggests that treatment should be initiated as
      early as possible. However, despite the fact that therapeutic options for MS have
      significantly been widened over the past decade there is still tremendous
      activity in the search for new treatment options for MS. One important
      development in the field is reflected by the substantial number of promising
      results for oral therapies. Various phase III clinical trials are currently being
      initiated or are already underway evaluating the efficacy of a variety of orally
      administered agents, including cladribine, teriflunomide, laquinimod, fingolimod
      and fumaric acid. It is hoped that these oral therapies for MS further broaden
      our armament for MS therapy. 

PMID- 25384865
TI  - Are there gender differences in neurologic and psychiatric disturbances?

PMID- 25384866
TI  - Gender differences in migraine.

PMID- 25384867
TI  - Special gender issues in psychiatry.
AB  - Significant gender differences exist in the course, manifestation and treatment
      of mental illness. Regardless of specific diagnosis age is one of the key factors
      in gender differences. Such differences between the sexes exist not only
      concerning origin and perpetuation of specific psychiatric diseases, they are
      also available and notable in specific fields of pharmacological and
      psychotherapeutically treatment. That review should sensitize clinicians for
      their responsibility to provide individualized, optimally effective, gender
      specific care to patients suffering from mental diseases in some special topics.
      It should be a short overview considering some important gender details
      illustrated in concern with the epidemiological background, the symptoms and
      general used psychiatric treatment strategies of some frequent psychiatric
      diagnoses. 

PMID- 25384868
TI  - Gender differences in epilepsy.

PMID- 25384869
TI  - Immune dysfunction, depression and neurodegeneration.

PMID- 25384870
TI  - Changes in immune and endocrine systems in posttraumatic stress disorder -
      prospective study.
AB  - INTRODUCTION AND AIM: Posttraumatic stress disorder (PTSD) is associated with
      increased medical morbidity, particularly from the autoimmune and cardiovascular
      diseases. Changes in the endocrine and immune system are key mediators in this
      process. The aim of our study was to investigate weather hormones (cortisol and
      prolactin), proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha)), components of HPA-axis (lymphocyte expression of
      glucocorticoid receptor (GR)), immune function (natural killer cell cytotoxicity)
      and peripheral blood percentages of various lymphocyte subpopulations (T cells,
      helper T cells, cytotoxic T cells, B cells and natural killer cells) change in
      patients with posttraumatic stress disorder over time.

PMID- 25384871
TI  - Immunological and histochemical analyses of cerebrospinal fluid and peripheral
      blood from patients with neurological and psychiatric disorders.
AB  - Epidemiological, clinical and post mortem studies indicate that inflammatory and
      immune reactions are involved in the pathomechanisms of affective and
      schizophrenic spectrum disorders. However, in psychiatric patients, only sporadic
      investigation on immunochemistry has been performed and information about
      immunofunction derived by investigation of immunocompetent cells in the CSF is
      not available to date. Here we present an interdisciplinary work of neurologists,
      psychiatrists and hemato-immunologists focusing on the immunology of psychiatric
      and neurological disorders. In a first study including 63 patients with therapy
      resistant affective and schizophrenic spectrum disorders we applied conventional,
      validated neurological CSF investigation such as analysis of albumin, IgG, IgA,
      IgM, oligoclonal IgG and specific antibodies, cell count and interpreted the data
      by Reibergrams. In a second study, we applied the highly sensitive and specific
      multicolour flowcytometry of paired samples of CSF and peripheral blood cells to
      characterize the immunostatus of psychiatric and neurological patients. We
      demonstrate that flowcytometry technology constitutes an appropriate method to
      investigate subsets of lymphocytes even with low CSF cell numbers, and therefore
      as a promising diagnostic tool for routine purposes in the differential diagnosis
      of psychiatric diseases. Furthermore, knowledge of the frequencies of T cell
      subsets such as the T regulatory cell type might open new avenues to models of
      psychiatric and neurological diseases as well as diagnostic and monitoring
      implications. 

PMID- 25384872
TI  - Cerebrospinal fluid analysis for diagnosis of noninflammatory, dementive and
      psychiatric diseases.
AB  - CSF analysis contributes to differential diagnosis of noninflammatory diseases
      by: 1) exclusion of a chronic or acute inflammation. 2) detection of particular
      brain-derived proteins, surrogate markers, corresponding to the suggested
      diagnosis (tumor, dementia, brain hypoxia, hemorrhage, autoimmune disease,
      psychiatric disease, metabolic disorder, rhinorhea, Table 1) and 3. differential
      cell count in CSF. Interpretation of brain-derived proteins in CSF uses absolute
      concentrations (in contrast to CSF/serum quotients for blood-derived proteins)
      and must discriminate between different sources: Neuronal or glial proteins like
      NSE, or tau protein are evaluated using their absolute concentrations in CSF for
      maximal sensitivity without reference to QAlb. The leptomeningeal proteins like
      beta trace or cystatin C are evaluated as absolute concentrations with reference
      to QAlb. As application examples we review the group of dementive and psychiatric
      diseases. Alzheimer's disease, Parkinson's disease dementia, Lewy-body disease
      and frontotemporal dementia are the major causes of neurodegenerative memory
      impairment and dementia. Combined analysis of Tau-Protein and Beta Amyloid 1-42
      in CSF represent the classic approach, meanwhile extended with further surrogate
      markers. In 15% of psychiatric patients with schizophrenic or affective disorders
      an inflammatory process could be detected which points to a brain-organic
      involvement. In 24% of these patients with a psychiatric disease a moderately
      increased albumin quotient was observed as the only unexplained pathological
      sign. In psychiatric diseases it has to be regarded as a serious deficit not to
      make at least once a CSF analysis in the patients which could modify the
      diagnosis (in 6%). 

PMID- 25384873
TI  - History of personality disorders.

PMID- 25384874
TI  - Treatment choice in psychiatry? Would trainees choose similar treatments to those
      prescribed, and what influences decision-making? A survey of the European
      Federation of Trainees' (EFPT) Research Group.

PMID- 25384875
TI  - EEG-based brain imaging techniques in psychiatry.
AB  - Electroencephalography has probably represented the first modern and
      scientifically sound attempt to functionally explore the in vivo activity of the
      human brain and it has, since ever, attracted attention of psychiatrists, from
      both the clinical and the research viewpoint. Probably due to the limitations
      implied by their traditional low spatial resolution, the use of
      psychophysiological techniques in psychiatry has been not continuous over the
      last century; however, the availability of newer EEG-based brain imaging
      techniques has recently renovated some interest (1)). Furthermore, recent
      theories proposed that psychopathology may result from the failure to integrate
      the activity of different areas involved in cognitive processes, rather than from
      the impairment of one or more brain areas (2)); within this view, a reliable
      brain imaging tool should be able to explore the dynamics of complex interactions
      among brain regions, with high sensitivity to the subtle deviation in complex
      processes that last fractions of seconds; psychophysiological techniques, indeed,
      offer the possibility to explore the functional correlates of major psychiatric
      illnesses, as well as to understand of the effects of psychotropic drugs on the
      central nervous system, with incomparable time resolution. Finally, the recent
      technical possibility to combine different brain imaging approaches has further
      fostered a renovated enthusiasm to ward the use of EEG-based techniques in
      psychiatry. This contribution will provide an historical overview of the EEG
      based brain imaging techniques and an update on some recent advances concerning
      the use of such techniques within the psychiatric field. Finally, some examples
      of psychophysiological and ''multimodal'' imaging investigations in subjects with
      different psychiatric conditions will be provided. 

PMID- 25384876
TI  - Subjective well-being with antipsychotic treatment.

PMID- 25384877
TI  - Differences in cholesterol and metabolic syndrome between bipolar disorder men
      with and without suicide attempts.
AB  - Patient with mental illnesses such as schizophrenia and bipolar disorder have an
      increased prevalence of metabolic syndrome (MetS) and its components compared to
      general population. Among psychiatric disorders, bipolar disorder ranks highest
      in suicidality with a relative risk ratio of completed suicide of about 25
      compared to the general population. Regarding the biological hypotheses of
      suicidality, low blood cholesterol level has been extensively explored, although
      results are still conflicting. The aim of this study was to investigate whether
      there were differences in the serum cholesterol levels in hospitalized bipolar
      disorder men patients with history of suicide attempts (n= 20) and without
      suicide attempts (n= 20). Additionally, we investigated if there were differences
      in the prevalence of MetS according to NCEP ATP-III criteria in these two groups
      of patients. Results of the study indicated significantly lower serum cholesterol
      levels (P = 0.013) and triglyceride levels (P = 0.047), in the bipolar disorder
      men with suicide attempts in comparison to bipolar disorder men without suicide
      attempts. The overall prevalence of MetS was 11/40 (27.5%). On this particular
      sample it was higher in the non-attempters 8/20 (40.0%) than in attempters 3/20
      (15.0%) bipolar men group, but without statistical significance. Lower
      concentrations of serum cholesterol might be useful biological markers of
      suicidality in men with bipolar disorder. 

PMID- 25384878
TI  - Management of stroke in central and east Europe.

PMID- 25384879
TI  - Psychopathy, dissocial personality disorder, evil: forensic psychiatric aspects.

PMID- 25384880
TI  - Depth-selective microscopic observation of a photomobile liquid crystal polymer
      under UV illumination.
AB  - By using the depth selective imaging method, we studied the UV induced change in
      a photomobile liquid crystalline polymer film. With 1 MUm depth resolution, each
      slice inside the film was selectively observed. A network-like structure mixed
      with the ordered and disordered regions of molecules in the middle of the film,
      and a rubbed polymer layer at the bottom of the film were observed. In each slice
      of the film, the phase change induced by UV light was observed strongly dependent
      on the director direction, which indicates the ordering change of the liquid
      crystalline molecules in the director direction. It took several tens of seconds
      for the ordering change caused by the collaborative interaction between the
      molecules. Furthermore, it was suggested that the UV induced change travelled
      from the bottom layer to the middle layer on the micron order. 

PMID- 25384881
TI  - Evaluation of the photolysis of pharmaceuticals within a river by 2 year field
      observations and toxicity changes by sunlight.
AB  - To improve the risk assessment of pharmaceuticals, it is helpful to know how
      rapidly they are removed from river water. Direct photolysis by sunlight could be
      an important process, but so far few studies have attempted to compare modeled
      with actual losses in a river. Therefore, we quantified natural attenuation by
      monitoring 56 pharmaceuticals and personal care products over 2 full years in a
      2.6 km stretch of an urban river. In addition, to screen photoproducts, we used
      the Microtox test with Vibrio fischeri to evaluate changes in the toxicity of two
      photolabile pharmaceuticals, ketoprofen and diclofenac, under sunlight. During
      transport along the river stretch, ketoprofen and the photolabile pharmaceutical
      furosemide were attenuated by median values of 77% and 39%. The observed
      attenuation showed good agreement with photochemical attenuation estimated by an
      existing method at each sampling, suggesting that the method appeared to be
      effective for estimating the direct photolysis of the pharmaceuticals during
      river transport. The toxicity of diclofenac decreased under sunlight, while that
      of ketoprofen increased immediately after exposure (around 12 times in EC20) and
      remained high, indicating the existence of toxic and photostable photoproducts of
      ketoprofen. Therefore, ecological risks of photolabile pharmaceuticals may
      increase during river transport in some cases, indicating the necessity to
      incorporate their photoproducts into the estimation method. 

PMID- 25384882
TI  - Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous
      cell carcinoma.
AB  - The recent development of human genome studies has demonstrated the possibility
      of alteration of several genes as oncogenic driver mutations of lung squamous
      cell carcinoma (SQCC). FGFR1, PIK3CA and SOX2 genes have been recognized as
      candidate driver genes of SQCC. The aim of the present study was to evaluate
      FGFR1, PIK3CA and SOX2 protein expression in SQCC and determine whether the
      expression of these can be used as prognostic biomarkers. We evaluated the
      relationships between FGFR1, PIK3CA and SOX2 expression by immunohistochemical
      analysis and overall survival in lung SQCC patients with stage I-III that
      originated from China, United States and Japan. FGFR1-positive, PIK3CA-negative
      and SOX2-positive staining each showed trends toward better survival, although
      the differences were not statistically significant in a Chinese cohort of 57
      patients. Patients with PIK3CA-negative and SOX2-positive staining (PIK3CA(
      )/SOX2(+)) showed better prognosis compared with those with PIK3CA-positive or
      SOX2-negative staining in the Chinese cohort (p=0.04). The robustness of PIK3CA(
      )/SOX2(+) classification as having prognostic significance was validated in an
      independent set of 66 Japanese cohort patients (p=0.007). Japanese SQCC patients
      with stage I were evaluated separately and PIK3CA(-)/SOX2(+) cases had
      significantly better survival than the group with PIK3CA-positive or SOX2
      negative status (p=0.03). In univariate and multivariable Cox proportional
      hazards models of Asian stage I patients, the PIK3CA(-)/SOX2(+) classification
      was statistically significantly associated with survival and was an independent
      prognostic factor. Classification by PIK3CA and SOX2 protein expression is useful
      for predicting the prognosis of Asian patients with lung SQCC with stage I.

PMID- 25384883
TI  - Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in
      peripheral blood cells and cervical tissue samples of females with cervical
      intraepithelial lesions and squamous cervical cancer.
AB  - High oncogenic risk human papillomaviruses (HPVs) are closely associated with
      cancer of the cervix. However, HPV infection alone may not be sufficient to cause
      cervical cancer, and other factors or cofactors may have a cumulative effect on
      the risk of progression from cervical HPV infection to cancer. The present study
      investigates the cytosine-adenine (CA) repeat polymorphism in the P1 promoter
      region of the insulin-like growth factor-1 (IGF-1) gene among cervical
      precancerous and cancer patients and healthy control females. The association
      between these polymorphisms, tissue and blood serum levels of IGF-1, and cervical
      cancer risk and progression is evaluated. The material for analysis consisted of
      blood cells and postoperative tissues from patients diagnosed with low-grade
      squamous intraepithelial lesions (L-SILs), high-grade squamous intraepithelial
      lesions (H-SILs) and invasive cervical cancer (ICC). A polymerase chain reaction
      amplification and the sequencing of DNA were used for the identification of (CA)n
      repeats in the IGF-1 P1 region and detection of HPV DNA. The blood serum
      concentration of IGF was determined by enzyme-linked immunosorbent assay. The
      identification of the IGF-1 protein in the cervical tissues was performed by
      immunohistochemical analysis. The range of the length of the CA repeats in the
      study DNA was 11 to 21. However, the most common allele length and genotype in
      the control and study patients from serum and tissues was 19 CA repeats and a
      homozygous genotype of CA19/19. Statistically significant differences in the
      concentration of IGF-1 in the blood serum were observed between H-SILs and
      controls, only (p=0.047). However, the concentration of IGF-1 in the group of
      females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group
      of patients with H-SIL (P=0.041) and ICC (P=0.048) in comparison with the control
      group. An association was detected between CA repeat length <19 and/or >19, IGF
      concentration in blood serum and tissues and the development of cervical cancer. 

PMID- 25384884
TI  - Distinct composition of the oral indigenous microbiota in South Korean and
      Japanese adults.
AB  - A comparison of national surveys on oral health suggested that the population of
      South Korea has a better periodontal health status than that of Japan, despite
      their similar inherent backgrounds. Here, we investigated differences in oral
      bacterial assemblages between individuals from those two countries. To exclude
      potential effects of oral health condition on the microbiota, we selected 52
      Korean and 88 Japanese orally healthy adults (aged 40-79 years) from the
      participants of two cohort studies, the Yangpyeong study in South Korea and the
      Hisayama study in Japan, and compared the salivary microbiomes. The microbiota of
      the Japanese individuals comprised a more diverse community, with greater
      proportions of 17 bacterial genera, including Veillonella, Prevotella, and
      Fusobacterium, compared to the microbiota of the Korean individuals. Conversely,
      Neisseria and Haemophilus species were present in much lower proportions in the
      microbiota of the Japanese individuals than the Korean individuals. Because
      higher proportions of Prevotella and Veillonella and lower proportions of
      Neisseria and Haemophilus in the salivary microbiome were implicated in
      periodontitis, the results of this study suggest that the greater proportion of
      dysbiotic oral microbiota in the Japanese individuals is associated with their
      higher susceptibility to periodontitis compared to the Korean individuals. 

PMID- 25384885
TI  - Identification and management of toxicities from immune checkpoint-blocking
      drugs.
AB  - Immune checkpoint-blocking drugs such as ipilimumab, pembrolizumab, and nivolumab
      have demonstrated clinical efficacy as anticancer agents. Through modulation of
      immunoregulatory molecules, these novel therapeutics can produce durable cancer
      remissions in a variety of tumor types. As these medications are administered to
      an increasing number of patients, clinicians must be able to recognize and treat
      the associated immune-related side effects. This review summarizes the unique
      mechanisms of toxicity associated with immune checkpoint-blocking drugs,
      appropriate steps in patient evaluation, and strategies for mitigating risk and
      optimizing patient outcomes. Although the management of each patient receiving
      immune checkpoint-blockade therapy must be individualized, a conceptual framework
      upon which to base a multidisciplinary approach to best practices will help
      oncology practitioners deliver safe and effective care. 

PMID- 25384886
TI  - Prognostic and predictive markers for the new immunotherapies.
AB  - Blocking the programmed cell death 1 (PD-1) pathway with monoclonal antibodies
      has shown promising antitumor responses in clinical trials, with less toxicity
      than has been seen with prior immune therapies such as interleukin 2 and
      ipilimumab. Pembrolizumab, an anti-PD-1 antibody, recently gained US Food and
      Drug Administration (FDA) accelerated approval for the treatment of patients with
      ipilimumab-refractory melanoma, while nivolumab, another anti-PD-1 antibody, and
      MPDL3280A, an anti-programmed cell death 1 ligand (PD-L1) antibody, have been
      granted FDA "breakthrough designation" for treatment of subsets of patients with
      refractory Hodgkin lymphoma and metastatic bladder cancer, respectively.
      Encouraging antitumor activity has also been seen with these agents in patients
      with other malignancies, including non-small-cell lung cancer and head and neck
      cancer, tumors not previously thought to be immune-responsive. PD-L1 expression
      has emerged as a potential predictive biomarker for PD-1-directed therapy.
      Multiple, distinct, companion assays for PD-L1 positivity have been developed,
      but there is as yet no comparison, standardization, or prospective validation of
      these assays. PD-L1 expression on tumor cells and/or the tumor-immune infiltrate
      is likely only part of the predictive model necessary for selecting patients
      predisposed to respond to monotherapy. Additional predictive biomarkers are
      necessary to identify patients most likely to benefit from PD-1-based combination
      therapy, since tumor cell PD-L1 expression appears to have limited predictive
      value in this setting. 

PMID- 25384887
TI  - Critical appraisal of studies measuring quality of life in juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: To critically evaluate studies purporting to measure quality of life
      (QOL) or health-related QOL (HRQOL) in juvenile idiopathic arthritis (JIA) by
      assessing the face validity of studies via a predefined set of criteria based on
      Gill and Feinstein (1994). METHODS: Systematic review was conducted of studies in
      Medline, Embase, and PsycInfo purporting to measure QOL or HRQOL in JIA. Studies
      were evaluated based on a set of 8 yes/no criteria set forth by Gill and
      Feinstein in 1994. RESULTS: Thirty-four of 50 studies (68%) purported to measure
      HRQOL, 13 of 50 (26%) measured QOL, and 3 of 50 (6%) measured both QOL and HRQOL.
      The descriptive analysis of studies is as follows: 22 of 50 studies (44%)
      explained and defined the authors' meaning of QOL or HRQOL, 42 of 50 studies
      (84%) stated and explained the domains of the instruments used to measure QOL and
      HRQOL, authors gave reasons for using a particular instrument in 25 of 50 studies
      (50%), 14 of 50 studies (28%) asked the patients to give their own global rating,
      4 of 50 study authors (8%) tried to differentiate QOL from HRQOL, 5 of 50 authors
      (10%) provided an opportunity for patients to add items to an instrument, 30 of
      50 study authors (60%) reported providing the patients with an opportunity to
      rate items of importance, and 18 of 50 studies (36%) reported an overall
      composite score for QOL or HRQOL. CONCLUSION: Our results show that the face
      validity of studies measuring QOL in JIA is not up to the standards and
      recommendations set forth by Gill and Feinstein in 1994.

PMID- 25384889
TI  - Cathodoluminescence and photoconductive characteristics of single-crystal ternary
      CdS/CdSe/CdS biaxial nanobelts.
AB  - The cathodoluminescence and optoelectronic properties based on an individual
      CdS/CdSe/CdS biaxial nanobelt are revealed in the present study. Both typical CdS
      and CdSe emissions are detected from as-grown CdS/CdSe/CdS nanobelts. The
      photodetector based on this nanobelt exhibits high sensitivity and excellent
      cycle stability. This opens a door to rational design of germanium chalcogenide
      compounds with unique optical properties. 

PMID- 25384888
TI  - Deletion of Drosophila Nopp140 induces subcellular ribosomopathies.
AB  - The nucleolar and Cajal body phosphoprotein of 140 kDa (Nopp140) is considered a
      ribosome assembly factor, but its precise functions remain unknown. To approach
      this problem, we deleted the Nopp140 gene in Drosophila using FLP-FRT
      recombination. Genomic PCR, reverse transcriptase-PCR (RT-PCR), and
      immunofluorescence microscopy confirmed the loss of Nopp140, its messenger RNA
      (mRNA), and protein products from all tissues examined. Nopp140-/- larvae
      arrested in the second instar stage and most died within 8 days. While nucleoli
      appeared intact in Nopp140-/- cells, the C/D small nucleolar ribonucleoprotein
      (snoRNP) methyltransferase, fibrillarin, redistributed to the nucleoplasm in
      variable amounts depending on the cell type; RT-PCRs showed that 2'-O-methylation
      of ribosomal RNA (rRNA) in Nopp140-/- cells was reduced at select sites within
      both the 18S and 28S rRNAs. Ultrastructural analysis showed that Nopp140-/- cells
      were deficient in cytoplasmic ribosomes, but instead contained abnormal electron
      dense cytoplasmic granules. Immunoblot analysis showed a loss of RpL34, and
      metabolic labeling showed a significant drop in protein translation, supporting
      the loss of functional ribosomes. Northern blots showed that pre-RNA cleavage
      pathways were generally unaffected by the loss of Nopp140, but that R2
      retrotransposons that naturally reside within the 28S region of normally silent
      heterochromatic Drosophila ribosomal DNA (rDNA) genes were selectively expressed
      in Nopp140-/- larvae. Unlike copia elements and the related R1 retrotransposon,
      R2 expression appeared to be preferentially dependent on the loss of Nopp140 and
      not on environmental stresses. We believe the phenotypes described here define
      novel intracellular ribosomopathies resulting from the loss of Nopp140. 

PMID- 25384891
TI  - Making sense of the noise: Replication difficulties of Correll's (2008)
      modulation of 1/f noise in a racial bias task.
AB  - Correll (Journal of Personality and Social Psychology, 94, 48-59, 2008; Study 2)
      found that instructions to use or avoid race information decreased the emission
      of 1/f noise in a weapon identification task (WIT). These results suggested that
      1/f noise in racial bias tasks reflected an effortful deliberative process,
      providing new insights regarding the mechanisms underlying implicit racial
      biases. Given the potential theoretical and applied importance of understanding
      the psychological processes underlying implicit racial biases - and in light of
      the growing demand for independent direct replications of findings to ensure the
      cumulative nature of our science - we attempted to replicate Correll's finding in
      two high-powered studies. Despite considerable effort to closely duplicate all
      procedural and methodological details of the original study (i.e., same cover
      story, experimental manipulation, implicit measure task, original stimuli, task
      instructions, sampling frame, population, and statistical analyses), both
      replication attempts were unsuccessful in replicating the original finding
      challenging the theoretical account that 1/f noise in racial bias tasks reflects
      a deliberative process. However, the emission of 1/f noise did consistently
      emerge across samples in each of our conditions. Hence, future research is needed
      to clarify the psychological significance of 1/f noise in racial bias tasks.

PMID- 25384892
TI  - When more data steer us wrong: replications with the wrong dependent measure
      perpetuate erroneous conclusions.
AB  - There is a replication crisis in science, to which psychological research has not
      been immune: Many effects have proven uncomfortably difficult to reproduce.
      Although the reliability of data is a serious concern, we argue that there is a
      deeper and more insidious problem in the field: the persistent and dramatic
      misinterpretation of empirical results that replicate easily and consistently.
      Using a series of four highly studied "textbook" examples from different research
      domains (eyewitness memory, deductive reasoning, social psychology, and child
      welfare), we show how simple unrecognized incompatibilities among dependent
      measures, analysis tools, and the properties of data can lead to fundamental
      interpretive errors. These errors, which are not reduced by additional data
      collection, may lead to misguided research efforts and policy recommendations. We
      conclude with a set of recommended strategies and research tools to reduce the
      probability of these persistent and largely unrecognized errors. The use of
      receiver operating characteristic (ROC) curves is highlighted as one such
      recommendation. 

PMID- 25384893
TI  - 1,1-Alkenylboration of diarylphosphino-enynes: convenient synthetic entry to
      vicinal P/B Lewis pairs at extended conjugated pi-frameworks.
AB  - Alkenylboranes R-CH=CH-B(C6F5)2 undergo carbon-carbon coupling by means of 1,1
      alkenylboration with diarylphosphino-enynes to give substituted conjugated
      hexatriene derivatives that bear a vicinal pair of B(C6F5)2 Lewis acid and PAr2
      Lewis base functionalities at their central carbon portions. A series of six
      examples was prepared and all compounds were characterized by X-ray diffraction.
      Consecutive reactions of two selected examples were carried out.

PMID- 25384894
TI  - Feasibility, reliability, and validity of the Japanese version of the
      Postoperative Quality of Recovery Scale: a first pilot study.
AB  - The Postoperative Quality of Recovery Scale (PQRS) is a multi-domain tracking
      scale to assess recovery after surgery. The PQRS is used in seven countries and
      five languages; however, the Japanese version of the PQRS (PQRSj) has not been
      established. We therefore translated the PQRS into Japanese, and examined the
      feasibility, reliability and validity of the PQRSj. The time taken to complete
      the test was measured to assess feasibility. Cronbach's alpha was calculated to
      assess reliability. The Mini Mental State Examination (MMSE) and the Japanese
      version of the Quality of Recovery Scale 40 (QoR-40 J) were performed for
      comparison with the PQRSj (validity). Fifty-one patients were enrolled in the
      study. The mean completion time was 3.9 min for baseline (feasibility).
      Cronbach's alpha was between 0.40 and 0.94 in each domain (reliability). A
      relationship was shown between cognitive domain and MMSE at baseline (r = 0.65, P
      < 0.01); however, no relationship was found between the other domains and the
      MMSE and QoR-40 J. Ceiling effects were observed in 78% of the questions. These
      results indicate that the PQRSj can be used to assess recovery after surgery,
      although it may be better to revise some of the questions to improve the validity
      of the PQRSj.

PMID- 25384895
TI  - Facilitated communication and authorship: a systematic review.
AB  - Facilitated Communication (FC) is a technique whereby individuals with
      disabilities and communication impairments allegedly select letters by typing on
      a keyboard while receiving physical support, emotional encouragement, and other
      communication supports from facilitators. The validity of FC stands or falls on
      the question of who is authoring the typed messages--the individual with a
      disability or the facilitator. The International Society for Augmentative and
      Alternative Communication (ISAAC) formed an Ad Hoc Committee on FC and charged
      this committee to synthesize the evidence base related to this question in order
      to develop a position statement. The purpose of this paper is to report this
      synthesis of the extant peer-reviewed literature on the question of authorship in
      FC. A multi-faceted search was conducted including electronic database searches,
      ancestry searches, and contacting selected authors. The authors considered
      synopses of systematic reviews, and systematic reviews, which were supplemented
      with individual studies not included in any prior reviews. Additionally,
      documents submitted by the membership were screened for inclusion. The evidence
      was classified into articles that provided (a) quantitative experimental data
      related to the authorship of messages, (b) quantitative descriptive data on the
      output generated through FC without testing of authorship, (c) qualitative
      descriptive data on the output generated via FC without testing of authorship,
      and (d) anecdotal reports in which writers shared their perspectives on FC. Only
      documents with quantitative experimental data were analyzed for authorship.
      Results indicated unequivocal evidence for facilitator control: messages
      generated through FC are authored by the facilitators rather than the individuals
      with disabilities. Hence, FC is a technique that has no validity.

PMID- 25384896
TI  - Air sparging for prevention of antibody disulfide bond reduction in harvested CHO
      cell culture fluid.
AB  - During the scale-up of several Chinese Hamster Ovary (CHO) cell monoclonal
      antibody production processes, significant reduction of the antibody interchain
      disulfide bonds was observed. The reduction was correlated with excessive
      mechanical cell shear during the harvest operations. These antibody reduction
      events resulted in failed product specifications and the subsequent loss of the
      drug substance batches. Several methods were recently developed to prevent
      antibody reduction, including modifying the cell culture media, using pre- and
      post-harvest chemical additions to the cell culture fluid (CCF), lowering the pH,
      and air sparging of the harvested CCF (HCCF). The work described in this paper
      further explores the option of HCCF air sparging for preventing antibody
      reduction. Here, a small-scale model was developed using a 3-L bioreactor to
      mimic the conditions of a manufacturing-scale harvest vessel and was subsequently
      employed to evaluate several air sparging strategies. In addition, these studies
      enabled further understanding of the relationships between cell lysis levels,
      oxygen consumption, and antibody reduction. Finally, the effectiveness of air
      sparging for several CHO cell lines and the potential impact on product quality
      were assessed to demonstrate that air sparging is an effective method in
      preventing antibody reduction.

PMID- 25384897
TI  - Application of propensity scores to explore the effect of public reporting of
      medicine use information on rational drug use in China: a quasi-experimental
      design.
AB  - BACKGROUND: Transparency has become a hottest topic and a growing movement in the
      health care system worldwide. This study used a quasi-experimental design method
      to explore whether public reporting of medicine use information can improve
      rational drug use. METHODS: 20 township hospitals and 274 doctors of City Y in
      Hubei Province, China were divided into the intervention and control groups on
      the basis of their characteristics. In the intervention group, the values and
      rankings of the average expenditure per prescription, percentage of prescriptions
      requiring antibiotics and percentage of prescriptions requiring injections of
      each hospital and doctor were publicly released to patients and doctors in an
      appropriate format monthly. Data were gathered both four months before and after
      the intervention. Propensity score matching (PSM) was used to minimize the
      observed covariate (gender, age, experience, education level, title, and monthly
      income) differences in the doctors' characteristics. 108 pairs of doctors were
      obtained after PSM. Chi-square test and t-test were employed to explore the
      effect of public reporting of medicine use information on rational drug use. The
      study was approved by the Committee of Tongji Medical College, Hua Zhong
      University of Science and Technology (IORG No: IORG0003571). RESULTS: In
      baseline, the average expenditure per prescription of the 274 doctors was 42.82
      RMB yuan (USD 6.97), the percentage of prescriptions requiring antibiotics was
      63.00%, and the percentage of prescriptions requiring injections was 70.79%, all
      higher than the average of Hubei Province and the standard recommended by WHO.
      Before the intervention all the three indicators were all comparable (p > 0.05),
      whereas after the intervention, a significant difference (p < 0.05) was found for
      the percentage of prescriptions requiring injections between the intervention
      (64.66%) and control groups (70.52%). CONCLUSIONS: Irrational drug use remains a
      policy issue in township hospitals in the study area. We demonstrated that
      publicly reporting medicine use information could decrease the percentage of
      prescriptions requiring injections in township hospitals in China, but this
      effect was not observed on prescription costs and antibiotics use. Analyses of
      the mechanism and long-term effect of public reporting of medicine use
      information are recommended for further studies.

PMID- 25384898
TI  - PTV margin definition in hypofractionated IGRT of localized prostate cancer using
      cone beam CT and orthogonal image pairs with fiducial markers.
AB  - PURPOSE: To evaluate PTV margins for hypofractionated IGRT of prostate comparing
      kV/kV imaging or CBCT. PATIENTS AND METHODS: Between 2009 and 2012, 20 patients
      with low- (LR), intermediate- (IR) and high-risk (HR) prostate cancer were
      treated with VMAT in supine position with fiducial markers (FM), endorectal
      balloon (ERB) and full bladder. CBCT's and kV/kV imaging were performed before
      and additional CBCT's after treatment assessing intra-fraction motion. CTVP for 5
      patients with LR and CTVPSV for 5 patients with IR/HR prostate cancer were
      contoured independently by 3 radiation oncologists using MRI. The van Hark
      formula (PTV margin =2.5Sigma +0.7sigma) was applied to calculate PTV margins of
      prostate/seminal vesicles (P/PSV) using CBCT or FM. RESULTS: 172 and 52 CBCTs
      before and after RT and 507 kV/kV images before RT were analysed. Differences
      between FM in CBCT or in planar kV image pairs were below 1 mm. Accounting for
      both random and systematic uncertainties anisotropic PTV margins were 5-8 mm for
      P (LR) and 6-11 mm for PSV (IR/HR). Random uncertainties like intra-fraction and
      inter-fraction (setup) uncertainties were of similar magnitude (0.9-1.4 mm).
      Largest uncertainty was introduced by CTV delineation (LR: 1-2 mm, IR/HR: 1.6-3.5
      mm). Patient positioning using bone matching or ERB-matching resulted in larger
      PTV margins. CONCLUSIONS: For IGRT CBCT or kV/kV-image pairs with FM are
      interchangeable in respect of accuracy. Especially for hypofractionated RT, PTV
      margins can be kept in the range of 5 mm or below if stringent daily IGRT,
      ideally including prostate tracking, is applied. MR-based CTV delineation
      optimization is recommended.

PMID- 25384899
TI  - Comparison of the circulating metabolite profile of PF-04991532, a
      hepatoselective glucokinase activator, across preclinical species and humans:
      potential implications in metabolites in safety testing assessment.
AB  - A previous report from our laboratory disclosed the identification of PF-04991532
      [(S)-6-(3-cyclopentyl-2-(4-trifluoromethyl)-1H-imidazol-1
      yl)propanamido)nicotinic acid] as a hepatoselective glucokinase activator for the
      treatment of type 2 diabetes mellitus. Lack of in vitro metabolic turnover in
      microsomes and hepatocytes from preclinical species and humans suggested that
      metabolism would be inconsequential as a clearance mechanism of PF-04991532 in
      vivo. Qualitative examination of human circulating metabolites using plasma
      samples from a 14-day multiple ascending dose clinical study, however, revealed a
      glucuronide (M1) and monohydroxylation products (M2a and M2b/M2c) whose
      abundances (based on UV integration) were greater than 10% of the total drug
      related material. Based on this preliminary observation, mass balance/excretion
      studies were triggered in animals, which revealed that the majority of
      circulating radioactivity following the oral administration of [14C]PF-04991532
      was attributed to an unchanged parent (>70% in rats and dogs). In contrast with
      the human circulatory metabolite profile, the monohydroxylated metabolites were
      not detected in circulation in either rats or dogs. Available mass spectral
      evidence suggested that M2a and M2b/M2c were diastereomers derived from
      cyclopentyl ring oxidation in PF-04991532. Because cyclopentyl ring hydroxylation
      on the C-2 and C-3 positions can generate eight possible diastereomers, it was
      possible that additional diastereomers may have also formed and would need to be
      resolved from the M2a and M2b/M2c peaks observed in the current chromatography
      conditions. In conclusion, the human metabolite scouting study in tandem with the
      animal mass balance study allowed early identification of PF-04991532 oxidative
      metabolites, which were not predicted by in vitro methods and may require
      additional scrutiny in the development phase of PF-04991532.

PMID- 25384900
TI  - Analysis of impact of geographic characteristics on suicide rate and
      visualization of result with Geographic Information System.
AB  - AIM: The aim of our study was to understand the geographic characteristics of
      Japanese communities and the impact of these characteristics on suicide rates.
      METHODS: We calculated the standardized mortality ratio from suicide statistics
      of 3318 municipalities from 1972 to 2002. Correlation analysis, multi-regression
      analysis and generalized additive model were used to find the relation between
      topographic and climatic variables and suicide rate. We visualized the relation
      between geographic characteristics and suicide rate on the map of Wakayama
      Prefecture, using the Geographic Information System. RESULTS: Our study showed
      that the geographic characteristics of each community are related with its
      suicide rate. The strongest factor among the geographic characteristics to
      increase the suicide rate was the slope of the habitable land. CONCLUSIONS: It is
      necessary to take the characteristics of each community into consideration when
      we work out measures of suicide prevention. Visualization of the findings on the
      local map should be helpful to promote understanding of problems and to share the
      information among various parties in charge of suicide prevention.

PMID- 25384901
TI  - Underuse of surveillance colonoscopy in patients at increased risk of colorectal
      cancer.
AB  - OBJECTIVES: Colorectal cancer incidence and mortality have declined over the past
      two decades, and much of this improvement is attributed to increased use of
      screening. Approximately 25% of patients who undergo screening colonoscopy have
      premalignant adenomas that require removal and follow-up colonoscopy. However,
      there are few studies of the use of surveillance colonoscopy in increased risk
      patients with previous adenomas. METHODS: We conducted a cross-sectional study to
      examine factors associated with underuse of surveillance colonoscopy among
      patients who are at increased risk for colorectal cancer. The study population
      consisted of patients with previously identified adenomatous polyps and who were
      due for follow-up colonoscopy. Patients were categorized as attenders (n=100) or
      non-attenders (n=104) on the basis of completion of follow-up colonoscopy.
      Telephone surveys assessed the use of surveillance colonoscopy across domains of
      predisposing patient characteristics, enabling factors, and patient need.
      Mutlivariable logistic regression was used to identify factors associated with
      screening completion. RESULTS: Perceived barriers, perceived benefits, social
      deprivation, and cancer worry were associated with attendance at colonoscopy.
      Higher benefits (odds ratio (OR) 2.37, 95% confidence interval (CI) 1.04-5.41)
      and cancer worry (OR 1.73, 95% CI 1.07-2.79) increased the odds of attendance at
      follow-up colonoscopy, whereas greater barriers (OR 0.49, 95% CI 0.28-0.88) and
      high social deprivation (>=2; OR 0.09, 95% CI 0.01-0.76) were associated with
      lower odds. CONCLUSIONS: Our results suggest that multilevel factors contribute
      to the use of surveillance colonoscopy in higher risk populations, many of which
      are amenable to intervention. Interventions, such as patient navigation, may help
      facilitate appropriate use of surveillance colonoscopy.

PMID- 25384903
TI  - Results of the BRD CAP project: progress toward identifying genetic markers
      associated with BRD susceptibility.
AB  - The Bovine Respiratory Disease Coordinated Agricultural Project (BRD CAP) is a 5
      year project funded by the United States Department of Agriculture (USDA), with
      an overriding objective to use the tools of modern genomics to identify cattle
      that are less susceptible to BRD. To do this, two large genome wide association
      studies (GWAS) were conducted using a case:control design on preweaned Holstein
      dairy heifers and beef feedlot cattle. A health scoring system was used to
      identify BRD cases and controls. Heritability estimates for BRD susceptibility
      ranged from 19 to 21% in dairy calves to 29.2% in beef cattle when using
      numerical scores as a semi-quantitative definition of BRD. A GWAS analysis
      conducted on the dairy calf data showed that single nucleotide polymorphism (SNP)
      effects explained 20% of the variation in BRD incidence and 17-20% of the
      variation in clinical signs. These results represent a preliminary analysis of
      ongoing work to identify loci associated with BRD. Future work includes
      validation of the chromosomal regions and SNPs that have been identified as
      important for BRD susceptibility, fine mapping of chromosomes to identify causal
      SNPs, and integration of predictive markers for BRD susceptibility into genetic
      tests and national cattle genetic evaluations. 

PMID- 25384902
TI  - A new clinically based staging system for perihilar cholangiocarcinoma.
AB  - OBJECTIVES: Current staging systems for perihilar cholangiocarcinoma (pCCA) are
      inadequate, as they are based on surgical pathology and therefore not relevant to
      unresectable patients. Clinical trials for potential targeted therapies for pCCA
      are hampered by the lack of an accurate, nonoperative staging system for
      predicting survival. We aimed at developing a clinical staging system for pCCA,
      which would be of prognostic relevance for all pCCA patients and help stratify
      patients for clinical trials. METHODS: Clinical information at the time of pCCA
      diagnosis of 413 patients seen at Mayo Clinic, Rochester, MN between 2002 and
      2010 was retrospectively analyzed. A survival predictive model was developed
      using Cox proportional hazards analysis. The performance of the staging system
      was compared with the current AJCC/UICC (the American Joint Committee on
      Cancer/the Union for International Cancer Control) 7th tumor-node-metastasis
      (TNM) staging system. RESULTS: Eastern Cooperative Oncology Group (ECOG) status,
      tumor size and number, vascular encasement, lymph node and peritoneal metastasis
      and CA 19-9 level were grouped into a four-tier staging system. The median
      survivals of stages I, II, III, and IV patients were 48.6, 21.8, 8.6, and 2.8
      months, with hazard ratios (95% confidence interval) of 1.0 (reference), 1.7 (1.1
      2.6), 3.1 (2.0-4.7), and 8.7 (5.2-14.5), respectively (P<0.0001). This staging
      system had greater concordance statistics (standard error) than the TNM staging
      system (0.725 (0.018) vs. 0.614 (0.017)), indicating better performance in
      predicting survival. CONCLUSIONS: This staging system, based on nonoperative
      information at the time of pCCA diagnosis, has excellent discriminatory power to
      classify patients into four prognostic stages. It could be useful to clinicians
      and for the design of clinical trials.

PMID- 25384904
TI  - Experience of a year of adult hospital dermatology consultations.
AB  - BACKGROUND: Dermatology consultations are frequently requested by inpatient
      hospital services. As inpatient dermatology services in the USA decline,
      dermatology hospital consultations are becoming increasingly important.
      OBJECTIVES: We aim to describe the spectrum of skin diseases encountered and the
      health care subspecialties requesting dermatology hospital consultations.
      METHODS: We performed a retrospective chart review of adult patient (age: >=18
      years) dermatology hospital consultations from January 1 to December 31, 2010. We
      examined patient demographic characteristics, consultation requesting services,
      and consultation diagnoses. RESULTS: Among dermatology services, 614 patients had
      674 separate inpatient dermatology consultations during 2010. Of these patients,
      55.9% were male (mean age: 59 years). In total, 205 consultations (30.4%) were
      requested by the internal medicine subspecialty, 137 (20.3%) by the hematology
      and oncology subspecialty, and 93 (13.8%) by the surgical subspecialty. The most
      common conditions seen by the hospital dermatology consulting service were skin
      infections (n = 125, 18.5%), dermatitis (n = 120, 17.8%), drug eruptions (n = 87,
      12.9%), chronic wounds and ulcers (n = 55, 8.1%), cutaneous neoplasms (n = 39,
      5.8%), graft-versus-host disease (n = 37, 5.5%), ecchymosis, purpura simplex or
      petechia (n = 26, 3.8%), intertrigo (n = 21, 3.1%), and urticaria (n = 20, 3.0%).
      CONCLUSIONS: The majority of consultations conducted by the dermatology hospital
      consulting service were for the management of common skin diseases, such as
      cutaneous infections, dermatitis, and drug eruptions. Most consultations were
      requested by the departments of internal medicine, hematology and oncology, and
      surgical services.

PMID- 25384905
TI  - Using a 2-stage strategy with respondent-driven sampling to recruit a hard-to
      reach population for a placebo microbicide gel clinical trial in Nellore, Andhra
      Pradesh (India).
AB  - Traditional recruitment methods for microbicide efficacy trials are labor
      intensive and may fail to reach high-risk hard-to-reach populations. We report
      duration of recruitment and lessons learned from a two-stage process to recruit
      female sex workers (FSWs) into a placebo microbicide trial, and examined
      characteristics associated with successful recruitment of peers who screened for
      and enrolled in the trial. FSWs were first recruited via respondent-driven
      sampling (RDS) to complete a survey and subsequently invited to screen for
      enrollment into a placebo microbicide trial taking place at a local clinic. It
      took 6 months to enroll 267 participants into the trial. Successful recruiters of
      peers who enrolled were more likely to have enrolled themselves (AOR 2.0, CI 1.3
      2.9) and less likely to visit Nellore city (AOR 0.5, CI 0.3-0.9). Recruitment of
      FSWs via a two-stage recruitment strategy with RDS can be a good option for
      future clinical trials. 

PMID- 25384906
TI  - High HIV Prevalence among Men who have Sex with Men in a Time-Location Sampling
      Survey, Sao Paulo, Brazil.
AB  - We conducted a time-location sampling sero-behavioral surveillance survey of men
      who have sex with men (MSM) in Sao Paulo, Brazil, the largest city in Latin
      America and the Southern Hemisphere (N = 1,217 interviewed with serological
      results for 771). HIV prevalence was 15.4 % (95 % CI 11.6-20.1), with only 45.8 %
      previously aware of their infection. HIV prevalence achieved 6.4 % among youth 18
      24 years and was higher among MSM with lower socio-economic status. In
      multivariate analysis, correlates of HIV were older age, gay identity, lower
      socio-economic status, social networks with HIV-positive MSM, receptive anal sex,
      and internet sex partners. Policy change towards increasing avenues for HIV
      testing coupled with antiretroviral treatment regardless of CD4 count or stage of
      disease stand to benefit the MSM community if scaled up fast enough. 

PMID- 25384907
TI  - Perceptions and Experiences with the VOICE Adherence Strengthening Program (VASP)
      in the MTN-003 Trial.
AB  - The VOICE Adherence Strengthening Program (VASP) was implemented in May 2011 to
      improve adherence counseling in VOICE (MTN-003), a multisite placebo-controlled
      trial of daily oral or vaginal tenofovir-based Pre-Exposure Prophylaxis (PrEP).
      Anonymous baseline (N = 82) and final follow-up (N = 75) surveys were
      administered to counselors and pharmacists at 15 VOICE sites, and baseline (N =
      18) and final (N = 26) qualitative in-depth interviews were conducted with
      purposively selected counseling staff at 13 VOICE sites. Qualitative interviews
      with VOICE participants (N = 38) were also analyzed for segments related to
      counseling. Behavioral and biological measures of product use collected in the 6
      months prior to VASP implementation were compared to those collected during the 6
      months following implementation. Results show that the majority of staff
      preferred VASP and thought that participants preferred VASP over the previous
      education and counseling strategy, although there was no evidence to suggest that
      participants noticed modifications in the counseling approach. No meaningful
      changes were observed in pre/post levels of reported use or drug detection.
      Interpretation of results is complicated by mid-trial implementation of VASP and
      its proximity to early closure of oral and vaginal tenofovir study arms because
      of futility.

PMID- 25384908
TI  - Interspecific and host-related gene expression patterns in nematode-trapping
      fungi.
AB  - BACKGROUND: Nematode-trapping fungi are soil-living fungi that capture and kill
      nematodes using special hyphal structures called traps. They display a large
      diversity of trapping mechanisms and differ in their host preferences. To provide
      insights into the genetic basis for this variation, we compared the transcriptome
      expressed by three species of nematode-trapping fungi (Arthrobotrys oligospora,
      Monacrosporium cionopagum and Arthrobotrys dactyloides, which use adhesive nets,
      adhesive branches or constricting rings, respectively, to trap nematodes) during
      infection of two different plant-pathogenic nematode hosts (the root knot
      nematode Meloidogyne hapla and the sugar beet cyst nematode Heterodera
      schachtii). RESULTS: The divergence in gene expression between the fungi was
      significantly larger than that related to the nematode species being infected.
      Transcripts predicted to encode secreted proteins and proteins with unknown
      function (orphans) were overrepresented among the highly expressed transcripts in
      all fungi. Genes that were highly expressed in all fungi encoded endopeptidases,
      such as subtilisins and aspartic proteases; cell-surface proteins containing the
      carbohydrate-binding domain WSC; stress response proteins; membrane transporters;
      transcription factors; and transcripts containing the Ricin-B lectin domain.
      Differentially expressed transcripts among the fungal species encoded various
      lectins, such as the fungal fruit-body lectin and the D-mannose binding lectin;
      transcription factors; cell-signaling components; proteins containing a WSC
      domain; and proteins containing a DUF3129 domain. A small set of transcripts were
      differentially expressed in infections of different host nematodes, including
      peptidases, WSC domain proteins, tyrosinases, and small secreted proteins with
      unknown function. CONCLUSIONS: This is the first study on the variation of
      infection-related gene expression patterns in nematode-trapping fungi infecting
      different host species. A better understanding of these patterns will facilitate
      the improvements of these fungi in biological control programs, by providing
      molecular markers for screening programs and candidates for genetic manipulations
      of virulence and host preferences.

PMID- 25384909
TI  - Comparison of laparoscopic and open colonic resection within fast-track and
      traditional perioperative care pathways: Clinical outcomes and in-hospital costs.
AB  - BACKGROUND: This study examined short-term clinical outcomes and in-hospital
      costs of laparoscopic and open colonic resection within fast-track and
      traditional care pathways. MATERIAL AND METHODS: A case-control study was
      performed. From 2007 to 2009, 116 patients underwent laparoscopic or open colonic
      resection for benign or malignant disease within fast-track care pathway. The
      control group consisted of 116 age-, sex-, comorbidity-, type of surgery-, and
      diagnosis-matched patients who received a traditional perioperative care from
      2000 to 2007. The main measures of outcome were postoperative hospital stay and
      in-hospital costs, with 30-day mortality, morbidity, reoperation, and readmission
      rates as secondary outcomes. RESULTS: The study groups were well balanced for
      baseline characteristics. Postoperative hospital stay was shorter in the fast
      track than in the control group: laparoscopic resection median 3 versus 5 days (p
      < 0.001) and open resection 4 versus 7 days (p < 0.001). In multivariate analysis
      fast-track care, laparoscopic surgery and complications were independent
      determinants affecting the length of hospital stay. Overall, there was a trend
      toward lower in-hospital costs in the fast-track group compared with the
      traditional care group, but the difference was not statistically significant.
      Open surgery within fast-track care was the least costly option compared to
      laparoscopic or open surgery within traditional care but not significantly so
      when compared with laparoscopy within fast-track care. Intake of solid food and
      bowel function recovered 1 day earlier in the fast-track group than in the
      control group (p < 0.001). Complications were more frequent after open surgery
      than after laparoscopic surgery (23.3% vs 11.0%, p = 0.012). Reoperation and
      readmission rates were similar between the study groups. CONCLUSION: Laparoscopy
      improves the efficiency of fast-track perioperative care without significantly
      increasing in-hospital costs.

PMID- 25384910
TI  - Operative Treatment of Primary Hyperparathyroidism in Daycare Surgery.
AB  - OBJECTIVE: The standard of care for primary hyperparathyroidism is surgical
      removal of hyperfunctional parathyroid tissue. Here, we describe 20 patients with
      primary hyperparathyroidism who were treated surgically in the setting of daycare
      surgery. DESIGN: Prospective observational study. METHODS: A total of 20 patients
      with primary hyperparathyroidism were operated between March 2005 and May 2010.
      The follow-up period had a median of 41 weeks (5-245 weeks). Results are
      presented as mean (+/- standard deviation) or median (minimum-maximum). RESULTS:
      A total of 20 patients (15 women, mean age 54 +/- 14 years) were included. Nine
      patients were provided with post-operative calcium supplementation. One of the
      patients visited the emergency department the next day with paresthesia and
      normocalcemia; this patient was sent home. Four patients, without prophylaxis,
      also reported themselves to the emergency department. Only one had mild
      hypocalcemia (2.09 mmol/L) and was supplemented. Comparing the emergency
      department group (n = 5) with the others, we found that pre-operative calcium
      levels were similar (p = 0.40); however, the emergency department group had
      significantly lower post-operative calcium levels (2.27 +/- 0.14 vs 2.55 +/-
      0.25, p = 0.008) and the decrease-percentage was significantly higher (17.5% +/-
      5.4% vs 10.5% +/- 6.4%, p = 0.21). CONCLUSION: Parathyroidectomy in the daycare
      setting is feasible and safe. However, many patients return to the emergency
      department. This could be related to the strict information that is provided or
      due to a large decrease in their calcium levels, albeit normocalcemia. Calcium
      supplementation is cheap and safe, so we will provide all future patients with
      calcium supplementation and herewith aim to reduce the amount of emergency
      department visits.

PMID- 25384912
TI  - Mycostatic effect of recombinant dermcidin against Trichophyton rubrum and
      reduced dermcidin expression in the sweat of tinea pedis patients.
AB  - Trichophytosis, a common dermatophytosis, affects nearly 20-25% of the world's
      population. However, little is known about mechanisms for preventing colonization
      of Trichophyton on the skin. Dermcidin, an antimicrobial peptide that provides
      innate immunity to the skin and is constitutively secreted even in the absence of
      inflammatory stimulation, was studied to elucidate its antimycotic activity
      against Trichophyton. Recombinant dermcidin was determined to have antimycotic
      activity against Trichophyton rubrum, as evaluated by colony-forming unit (CFU)
      assays. The killing rate of dermcidin was 40.5% and 93.4% at 50 MUg/mL (the
      average dermcidin concentration in healthy subjects) and 270 MUg/mL,
      respectively. An effect of dermcidin treatment was found to be a reduction of the
      metabolic activity of Trichophyton as determined by nicotinamide adenine
      dinucleotide assay. Further, dermcidin concentrations in sweat of tinea pedis
      patients were found to be lower than those of healthy subjects. These findings
      suggest a mycostatic role for dermcidin, at normal sweat concentrations.
      Accordingly, we suspect that dermcidin, at normal sweat concentrations, inhibits
      growth of Trichophyton, where Trichophyton is subsequently eliminated in
      conjunction with epidermis turnover. Dermcidin, therefore, appears to play a role
      in the skin protection mechanism that prevents colonization of tinea pedis. 

PMID- 25384911
TI  - Development of photodynamic therapy regimens that control primary tumor growth
      and inhibit secondary disease.
AB  - Effective therapy for advanced cancer often requires treatment of both primary
      tumors and systemic disease that may not be apparent at initial diagnosis.
      Numerous studies have shown that stimulation of the host immune system can result
      in the generation of anti-tumor immune responses capable of controlling
      metastatic tumor growth. Thus, there is interest in the development of
      combination therapies that both control primary tumor growth and stimulate anti
      tumor immunity for control of metastatic disease and subsequent tumor growth.
      Photodynamic therapy (PDT) is an FDA-approved anticancer modality that has been
      shown to enhance anti-tumor immunity. Augmentation of anti-tumor immunity by PDT
      is regimen dependent, and PDT regimens that enhance anti-tumor immunity have been
      defined. Unfortunately, these regimens have limited ability to control primary
      tumor growth. Therefore, a two-step combination therapy was devised in which a
      tumor-controlling PDT regimen was combined with an immune-enhancing PDT regimen.
      To determine whether the two-step combination therapy enhanced anti-tumor
      immunity, resistance to subsequent tumor challenge and T cell activation and
      function was measured. The ability to control distant disease was also
      determined. The results showed that the novel combination therapy stimulated anti
      tumor immunity while retaining the ability to inhibit primary tumor growth of
      both murine colon (Colon26-HA) and mammary (4T1) carcinomas. The combination
      therapy resulted in enhanced tumor-specific T cell activation and controlled
      metastatic tumor growth. These results suggest that PDT may be an effective
      adjuvant for therapies that fail to stimulate the host anti-tumor immune
      response. 

PMID- 25384913
TI  - The long and winding road of foot disease in patients with diabetes.

PMID- 25384914
TI  - Difficult situations managing diabetic foot. Evidences and personal views: is to
      operate on patients with diabetic foot osteomyelitis old-fashioned?
AB  - Both medical and surgical approaches have been shown to be effective in the
      treatment of patients with diabetic foot osteomyelitis (DFO). In patients with
      risk factors of bad outcome such as major bone destruction, concomitant acute
      infections requiring drainage, problems in limb perfusion, highly resistant
      bacteria, and contraindication for or patient refusal of prolonged antibiotic
      therapy, the choice of surgery does not require further discussion. On the
      contrary, modest changes of bone on imaging assessment and no limiting factors as
      described above make medical treatment an attractive option for patients with DFO
      provided the rules of antibiotic treatment of chronic osteomyelitis are
      respected. The key question may not be to oppose surgery and medical treatment
      but to identify patients who need surgery and those who do not. There is
      currently no classification or score system that may allow physician to decide
      whether medical or surgical approach is best adapted to a given patient, and so
      both experience and skill of the multidisciplinary team appear paramount for
      guiding the choice of the best adapted ("tailored") strategy in a given patient.
      In this regard, it would be interesting to compare surgical and medical
      approaches for DFO that apparently may benefit from one or another (ie, bone
      lesions seen on plain radiographs of the foot but without bone fragmentation or
      multiple sites of osteomyelitis, no contraindication to prolonged antibiotic
      therapy, and location of bone involvement that may allow conservative surgery).
      Given the current available data on the therapeutic options of DFO, it appears
      that surgery for those patients is obviously not an old-fashioned option. 

PMID- 25384915
TI  - The role of surgical off-loading to prevent recurrent ulcerations.
AB  - Foot ulcerations in patients with diabetes are common. Most ulcers heal with
      conservative treatment, but recurrence is common. The pathway of ulcer
      development includes neuropathy, deformity, and trauma. The first attempt to
      avoid recurrence is by the use of shoes and insoles. When shoes and insoles fail,
      surgical correction of deformity leading to the ulcer can be attempted. This
      article reviews the most common procedures performed to heal ulcers or avoid
      recurrence. 

PMID- 25384916
TI  - Reduction of diabetic foot ulcer healing times through use of advanced treatment
      modalities.
AB  - Diabetic wounds are a major health care problem associated with delayed healing
      and high amputation rates. This review systematically evaluated newer wound care
      therapies for the treatment of diabetic wounds. More recent means of approaching
      diabetic foot ulcers include various dressings, off-loading shoes, and
      bioengineered skin constructs and growth factors. Electrical stimulation,
      phototherapy, electromagnetic fields, and shockwave therapy have been further
      proposed as potential treatments. A brief overview of these treatments is
      presented using peer-reviewed evidenced-based literature. A review of the
      literature demonstrated that treatment of diabetic wounds has focused on either
      prevention of the wounds in the form of off-loading shoes or adequate protective
      dressings or on direct treatment of wounds with bioengineered skin constructs,
      growth factors, or medical devices that accelerate wound healing. The authors'
      conclusion, following extensive literature review, is that although excellent
      national and international guidelines exist regarding suggested approaches to the
      treatment of the diabetic foot ulcer, there is no definitive or universal
      consensus on the choice of specific treatment modalities. The importance of
      optimizing comorbidities and the disease state, hemodynamics, local and
      peripheral skin and wound care, and metabolic challenges while reducing
      biological and bacterial burden and minimizing trauma remain the primary
      approach, followed by choice of the most appropriate treatment material or
      product. 

PMID- 25384919
TI  - Digital mucous cyst excision using a proximally based skin flap.
AB  - Mucous cysts of the fingers are benign ganglionic lesions arising generally from
      the distal interphalangeal joint that are more frequent between the fifth and
      seventh decades. They are usually asymptomatic; however, in certain cases such as
      pain or when the overlying skin is excessively attenuated, leading to breakdown
      and oozing of synovial fluid and potential risk of infection, surgical excision
      is recommended. In the present article a technique to excise the cyst while
      preserving its overlying attenuated skin is presented. 

PMID- 25384918
TI  - Mesenchymal stem cells can prevent alterations in behavior and neurogenesis
      induced by Abeta25-35 administration.
AB  - Mesenchymal stem cells (MSCs) are known to enhance neurogenesis in the dentate
      gyrus, as well as to modulate immune cell activity and inflammation. Easily
      obtained and expanded from the bone marrow and other tissues, MSCs have been
      proposed as candidates for stem cell therapy in various neurodegenerartive
      diseases. In the present study, we sought to explore these therapeutic properties
      of MSC on Abeta25-35-induced pathology when coadministered together. Apparently,
      coadministration of MSC prevented mild cognitive deficits observed following
      Abeta administration alone, by promoting microglial activation and rapid
      clearance of injected Abeta aggregates. Surprisingly, increased hippocampal
      neurogenesis was observed in the Abeta-injected animals and was normal in MSC
      coadministered animals just as in control animals. The observed increase in
      neurogenesis can be explained as a compensating mechanism responsible for the
      mild and temporary cognitive deficits observed in the Morris water maze assay in
      Abeta-injected animals. Interestingly, MSC engrafted not only to the hippocampus
      but were also detected in the choroid plexus. We thus conclude that MSC may act
      in multiple pathways to protect the CNS from Abeta pathology, while neurogenesis
      is a possible compensating mechanism; it is not always activated by MSC, which in
      turn may interact with local immune cells to regulate Abeta accumulation. 

PMID- 25384920
TI  - The use of dermal automesh for incidental hernia repair in abdominoplasty:
      Clinical, biochemical, and radiological results.
AB  - Abdominal wall hernias are often diagnosed on clinical examination or encountered
      intraoperatively during an abdominoplasty. The aim of this study is to evaluate
      the long-term results of the use of dermal automesh for the repair of incidental
      hernias during abdominoplasty operations, and to perform a comparative analysis
      of the biomechanical strengths of dermal automesh vs biological tissue graft.
      Between 2008-2012, dermal automesh was used in 12 patients for hernia repair.
      After repair of hernia, dermal automesh was applied over the repaired area in an
      onlay fashion. Postoperative follow-up was performed by physical examination and
      magnetic resonance imaging (MRI) of the abdominal wall. Biomechanical test was
      performed with prepared samples from excised abdominal panniculus for tensile
      strength and yield power. Mean age was 45 years (range = 36-54 years). Total
      follow-up was 26 (14-52) months. MRI studies showed that there were no hernias or
      defects of the anterior abdominal wall. The tensile strength of the dermal mesh
      was measured as 15.9 +/- 6.0 Mpa (6.4-24.5), maximum load before yield measured
      680 +/- 175.2 N (336.0-856.0). In conclusion, dermal automesh is a useful option
      for surgeons who encounter undiagnosed hernias during abdominoplasties. 

PMID- 25384921
TI  - Changes of serum cytokines-related Th1/Th2/Th17 concentration in patients with
      postmenopausal osteoporosis.
AB  - BACKGROUND: Postmenopausal osteoporosis is now hypothetically considered to be an
      autoimmune and inflammatory process in which many pro-inflammatory and T cell
      derived cytokines play important roles in the loss of bone mass. For instance,
      interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and tumor necrosis factor
      alpha (TNF-alpha) secreted by Th1 and IL-6, IL-4, and IL-10 secreted by Th2 have
      been shown to be involved in the pathogenesis of osteoporosis. Interleukin-17 (IL
      17) is a characteristic cytokine secreted by Th17 cells of the CD4 + subgroup.
      Although IL-17 has been shown to enhance bone resorption in ovariectomized mouse
      model, bone cells and genetic research, human-related studies of IL-17 are few.
      METHODS: According to WHO classification of osteoporosis by the T scores of BMD,
      the subjects were divided into the postmenopausal osteoporosis group (T scores<=
      2.5), the postmenopausal osteopenia group (-2.5 < T scores<-1), and the
      postmenopausal normal BMD group (T scores>=-1); 30 subjects in each group.
      Cytometric bead array (CBA) technique was employed for serum determination of the
      primary indexes including IL-17A, IL-2, IFN-gamma, TNF-alpha, IL-6, IL-4, and IL
      10 concentrations in the 90 volunteers. In the meantime, serum calcium,
      phosphorus, magnesium, and alkaline phosphatase concentrations were also
      determined in the patients. One-way analysis of variance (one-way ANOVA) was
      employed in data analysis to determine whether the testing results of various
      parameters had significant differences. The bivariate correlation was tested with
      the Pearson correlation coefficient. When p < 0.05, the difference was considered
      to have statistical significance. RESULTS: Serum IL-17A concentration was
      significantly higher in the postmenopausal osteoporosis group than in the
      postmenopausal osteopenia group and the postmenopausal normal BMD group, but the
      difference between the postmenopausal osteopenia group and the postmenopausal
      normal BMD group had no statistical significance. IL-17A was negatively
      correlated with BMD. To our knowledge, we discovered for the first time that
      serum concentrations of IFN-gamma and IL-4 were significantly lower in the
      postmenopausal osteoporosis group than in the postmenopausal normal BMD group;
      IFN-gamma and IL-4 were positively correlated with BMD. In addition, we also
      determined that BMI was negatively correlated with BMD; IL-17A was positively
      correlated with serum calcium. However, no significant differences in IL-6, TNF
      alpha, IL-2, and IL-10 were observed among the three groups; these three factors
      were not correlated with BMD. CONCLUSIONS: Our experiments have confirmed the
      roles of IL-17 in the pathogenesis of postmenopausal osteoporosis and in the
      promotion of bone resorption. Targeted therapy of IL-17, IFN-gamma, and IL-4 may
      be beneficial in the treatment of patients with postmenopausal osteoporosis. Our
      experiments have also confirmed the roles of IFN-gamma and IL-4 in the
      pathogenesis of postmenopausal osteoporosis and in the inhibition of bone
      resorption.

PMID- 25384922
TI  - Nanocomposites of tantalum-based pyrochlore and indium hydroxide showing high and
      stable photocatalytic activities for overall water splitting and carbon dioxide
      reduction.
AB  - Nanocomposites of tantalum-based pyrochlore nanoparticles and indium hydroxide
      were prepared by a hydrothermal process for UV-driven photocatalytic reactions
      including overall water splitting, hydrogen production from photoreforming of
      methanol, and CO2 reduction with water to produce CO. The best catalyst was more
      than 20 times more active than sodium tantalate in overall water splitting and 3
      times more active than Degussa P25 TiO2 in CO2 reduction. Moreover, the catalyst
      was very stable while generating stoichiometric products of H2 (or CO) and O2
      throughout long-term photocatalytic reactions. After the removal of In(OH)3, the
      pyrochlore nanoparticles remained highly active for H2 production from pure water
      and aqueous methanol solution. Both experimental studies and density functional
      theory calculations suggest that the pyrochlore nanoparticles catalyzed the water
      reduction to produce H2, whereas In(OH)3 was the major active component for water
      oxidation to produce O2.

PMID- 25384923
TI  - Intravoxel incoherent motion MRI evaluation for the staging of liver fibrosis in
      a rat model.
AB  - PURPOSE: To explore the characteristics of intravoxel incoherent motion (IVIM) in
      various stages of liver fibrosis, and their relationships with fibrotic stages in
      rats. MATERIALS AND METHODS: Fifty rats were given various doses of carbon
      tetrachloride (CCl4 ) to induce various fibrotic stages in rats; 15 untreated
      rats served as controls. Diffusion-weighted magnetic resonance imaging (MRI) was
      performed and eight b-values (0-800 s/mm(2) ) were applied to obtain IVIM
      parameters (D, pure molecular diffusion; f, perfusion fraction; D*,
      pseudodiffusion). The stages of liver fibrosis (stages F0-F4) were evaluated
      histologically using METAVIR scores. Fifty-seven rats (15 controls and 42 with
      fibrosis) were analyzed by nonparametric methods and receiver operating
      characteristic curves to determine diagnostic accuracy. RESULTS: Significant
      differences (P < 0.001) were found between stages (stages F0-F4) by D, f, D*, and
      apparent diffusion coefficient (ADC). There were inverse correlations between
      fibrosis stages and D, f, D*, ADC (r = -0.657, r = -0.631, r = -0.711 r = -0.719,
      respectively). Multivariate analysis showed that the combination models (D, f,
      D*) were better than the individual parameter (ADC) for the evaluation fibrosis
      stages (area under the curve [AUC]: 0.821-1.000 vs. AUC: 0.753-0.918) CONCLUSION:
      IVIM-derived parameters showed significant correlations with stages of liver
      fibrosis in a rat model.

PMID- 25384925
TI  - Are elderly construction workers sufficiently fit for heavy manual labour?
AB  - This study analysed the work ability of elderly construction workers. Forty male
      construction workers, 20 young (age < 33 yrs) and 20 senior (age>44 yrs) workers,
      were tested regarding aerobic power (VO2max) and muscle strength. The aerobic
      demand of a number of tasks in construction work was measured and compared with
      the workers' aerobic power. VO2max was higher for the young, and they performed
      better on most muscle strength tests. The measurements showed that about half of
      the senior workers had to use more than 30% of their maximum oxygen uptake on
      some tasks. In conclusion, because elderly construction workers decline in
      physical fitness, they are more exposed to overload when performing heavy manual
      work than are their younger peers. Increasing their individual fitness or
      adjusting their workload may be important for staying in the workforce for such
      workers. PRACTITIONER SUMMARY: Construction workers must occasionally perform
      strenuous work tasks that may endanger their safety. This was more often the case
      for elderly workers investigated here. Elderly workers should therefore be
      particularly observant of their physical fitness, and should possibly train
      during leisure time to improve their fitness.

PMID- 25384924
TI  - Problem solving after marginal artery injury during splenic flexure mobilization 
      a video vignette.

PMID- 25384927
TI  - Successful transcatheter occlusion of an anomalous pulmonary vein with dual
      drainage to the left atrium.
AB  - We describe a case of a scimitar syndrome "variant" where dual drainage existed
      from the right upper and middle pulmonary veins to the inferior vena cava and
      left atrium. Device closure of the anomalous vein at the level of the connection
      to the IVC was successful in achieving diversion of pulmonary venous flow to the
      left atrium. Vigilance during work-up of anomalous pulmonary venous drainage
      (whether isolated or associated with other cardiac defects that may be amenable
      to device closure) is important to define the presence of dual connections to the
      left atrium, in which case a less-invasive transcatheter approach may be
      feasible.

PMID- 25384928
TI  - Autologous total ossicular replacement prosthesis.
AB  - OBJECTIVE: To develop an autologous total ossicular replacement prosthesis with
      sustainable hearing results. METHODS: The ears of 40 patients, who had chronic
      otitis media with absent suprastructure of the stapes and long process of the
      incus, were repaired using the autologous total ossicular replacement technique.
      Post-operative results were evaluated after 6 and 12 months on the basis of
      average pure tone air conduction and average air-bone gap measured at 0.5, 1, 2
      and 3 kHz. RESULTS: Successful rehabilitation of pure tone average to 30 dB or
      less was achieved in 75 per cent of patients, and air-bone gap to 20 dB or less
      was attained in 82.5 per cent of patients. Overall mean improvement in air-bone
      gap was 23.9 +/- 8.5 dB (p < 0.001). Mean improvements in air-bone gap were
      significantly greater (p < 0.05) in the tympanoplasty only group (27.3 +/- 6.6
      dB) and the intact canal wall tympanoplasty group (25.9 +/- 6.3 dB) than in the
      canal wall down tympanoplasty group (16.3 +/- 8.9 dB). CONCLUSION: This paper
      describes an autologous total ossicular replacement prosthesis that is
      biocompatible, stable, magnetic resonance imaging compatible and, above all,
      results in sustainable hearing improvement.

PMID- 25384929
TI  - Diminishing returns and great potential: a comment on Pollack's & Reuter's review
      on tougher drug enforcement and prices.

PMID- 25384930
TI  - Yet another dimension of the ineffectiveness of supply-side interventions in
      illegal drug markets.

PMID- 25384931
TI  - Calibrating law enforcement and its purpose.

PMID- 25384932
TI  - Response to commentaries.

PMID- 25384934
TI  - Commentary on Ally et al. (2014): Increasing the price of cheap alcohol would
      contribute to decreasing health inequalities.

PMID- 25384933
TI  - Vested interests in addiction research and policy. Alcohol brand sponsorship of
      events, organizations and causes in the United States, 2010-2013.
AB  - BACKGROUND AND AIMS: There has been insufficient research attention to the
      alcohol industry's use of corporate sponsorship as a marketing tool. This paper
      provides a systematic investigation of the nature and extent of alcohol
      sponsorship-at the brand level-in the United States. METHODS: The study examined
      sponsorship of organizations and events in the United States by alcohol brands
      from 2010 to 2013. The top 75 brands of alcohol consumed by underage drinkers
      were identified based on a previously conducted national internet-based survey.
      For each of these brands, a systematic search for sponsorships was conducted
      using Google. The sponsorships were coded by category and type of sponsorship.
      RESULTS: We identified 945 sponsorships during the study period for the top 75
      brands consumed by underage drinkers. The most popular youth brands were far more
      likely to engage in sponsorship and to have a higher number of sponsorships. The
      identified sponsorships overwhelmingly associated alcohol brands with integral
      aspects of American culture, including sports, music, the arts and entertainment,
      and drinking itself. The most popular brands among underage drinkers were much
      more likely to associate their brands with these aspects of American culture than
      brands that were less popular among underage drinkers. CONCLUSIONS: Alcohol brand
      sponsorship must be viewed as a major alcohol marketing strategy that generates
      brand capital through positive associations with integral aspects of culture,
      creation of attractive brand personalities, and identification with specific
      market segments. Alcohol research, practice and policy should address this highly
      prevalent form of alcohol marketing.

PMID- 25384935
TI  - Commentary on Morgenstern et al. (2014): As channels for alcohol marketing
      continue to increase, so will alcohol marketing receptivity and youth drinking.

PMID- 25384936
TI  - Commentary on Nolan et al. (2014): Opiate substitution treatment and hepatitis C
      virus prevention: building an evidence base?

PMID- 25384937
TI  - Commentary on Reitzel et al. (2014): Is smoking cessation associated with worse
      comorbid substance use outcomes among homeless adults?

PMID- 25384938
TI  - Fortune or foe: the fatal harm caused by a gambling disorder.

PMID- 25384940
TI  - Estimation of a benchmark dose in the presence or absence of hormesis using
      posterior averaging.
AB  - U.S. Environment Protection Agency benchmark doses for dichotomous cancer
      responses are often estimated using a multistage model based on a monotonic dose
      response assumption. To account for model uncertainty in the estimation process,
      several model averaging methods have been proposed for risk assessment. In this
      article, we extend the usual parameter space in the multistage model for
      monotonicity to allow for the possibility of a hormetic dose-response
      relationship. Bayesian model averaging is used to estimate the benchmark dose and
      to provide posterior probabilities for monotonicity versus hormesis. Simulation
      studies show that the newly proposed method provides robust point and interval
      estimation of a benchmark dose in the presence or absence of hormesis. We also
      apply the method to two data sets on carcinogenic response of rats to 2,3,7,8
      tetrachlorodibenzo-p-dioxin. 

PMID- 25384944
TI  - Genetics: The Cancer Genome Atlas maps papillary thyroid cancer.

PMID- 25384948
TI  - Immunotherapy: Treatment of aggressive lymphomas with anti-CD19 CAR T cells.

PMID- 25384949
TI  - Gastrointestinal cancer: FOLFOXIRI-improving outcomes of metastatic colorectal
      cancer.

PMID- 25384943
TI  - The evolution of cancer surgery and future perspectives.
AB  - Surgery is the oldest oncological discipline, dating back thousands of years.
      Prior to the advent of anaesthesia and antisepsis 150 years ago, only the brave,
      desperate, or ill-advised patient underwent surgery because cure rates were low,
      and morbidity and mortality high. However, since then, cancer surgery has
      flourished, driven by relentless technical innovation and research. Historically,
      the mantra of the cancer surgeon was that increasingly radical surgery would
      enhance cure rates. The past 50 years have seen a paradigm shift, with the
      realization that multimodal therapy, technological advances, and minimally
      invasive techniques can reduce the need for, or the detrimental effects of,
      radical surgery. Preservation of form, function, and quality of life, without
      compromising survival, is the new mantra. Today's surgeons, no longer the
      uneducated technicians of history, are highly trained medical professionals and
      together with oncologists, radiologists, scientists, anaesthetists and nurses,
      have made cancer surgeries routine, safe, and highly effective. This article will
      review the major advances that have underpinned this evolution. 

PMID- 25384950
TI  - Induction of neural tissue markers by micronized human spinal cord implants.
AB  - The osteoinductive capacity of biological noncellular material has been widely
      recognized. Studies using bone morphogenetic proteins and acellular bone matrix
      demonstrate that host mesenchymal cells can be readily transformed into
      osteoprogenitor cells. The current study sought to determine whether another
      biological noncellular material, human spinal cord matrix, could induce
      transformation of host cells into a neural lineage. We demonstrate the formation
      of neural tissue and the expression of neural-specific lineage markers in host
      cells colonizing implanted spinal cord fragments and adjacent tissue along with
      the lack of expression of nonneural lineage markers. These studies demonstrate
      that the inductive capacity of biological noncellular material is not limited to
      the osteogenic lineage and suggest that acellular spinal cord matrix could be
      used to generate host-derived cells for use in neural repair and regeneration.

PMID- 25384951
TI  - Quality of life... on Earth.

PMID- 25384952
TI  - Relation between neuritic plaques and depressive state in Alzheimer's disease.
AB  - Meynen G, Van Stralen H, Smit JH, Kamphorst W, Swaab DF, Hoogendijk WJG. Relation
      between neuritic plaques and depressive state in Alzheimer's disease. BACKGROUND:
      To investigate for the first time in a prospective study the relationship between
      depressive state and the neuropathological hallmarks of Alzheimer's disease,
      using a scale for depressive symptoms in dementia, while controlling for clinical
      severity of dementia. METHOD: Within the framework of a prospective longitudinal
      study of depression in Alzheimer's disease, patients with dementia underwent a
      clinical evaluation every six months during the last years of their lives, using
      the Cornell scale for depression in dementia to assess depressive symptoms and
      using the Functional Assessment Staging scale to control for clinical severity of
      dementia. The brains of 43 Alzheimer patients were obtained. The last clinical
      evaluations prior to death together with post-mortem neuropathology measures were
      analysed. RESULTS: We found a correlation between the Cornell scores and the sum
      score for the density of neuritic plaques in the entire cortex (p = 0.027), and
      even stronger in the temporal cortex (p = 0.012). The observed correlations were
      independent of sex, age of death, clinical dementia severity and duration of
      Alzheimer's disease. CONCLUSIONS: This study shows a positive relationship
      between depressive state at time of death and the presence of neuritic plaques in
      Alzheimer's disease, which is independent of the clinical severity of dementia.

PMID- 25384953
TI  - Melancholic symptoms as assessed by the Hamilton Depression Rating Scale and
      outcomes with and without electroconvulsive therapy on an in-patient mood
      disorders unit.
AB  - Rasmussen KG, Stevens SR, Kung S, Mohan A. Melancholic symptoms as assessed by
      the Hamilton Depression Rating Scale and outcomes with and without
      electroconvulsive therapy on an in-patient mood disorders unit. BACKGROUND: We
      investigated whether 24-item Hamilton Rating Scale for Depression (HamD24)-based
      melancholia ratings correlated with treatment outcome, with special focus on
      whether electroconvulsive therapy (ECT) was used in depressed patients treated on
      an in-patient mood disorders unit. METHODS: We analysed the data on ECT- versus
      non-ECT-treated patients' outcomes relative to melancholia subscale scores. Two
      HamD24-based melancholia rating scale scores were computed for 201 depressed in
      patients at admission and discharge. Baseline melancholia ratings were analysed
      to see if they correlated with improvement in total HamD24 scores. We also tested
      to see if the melancholia subscales followed unimodal or bimodal distributions.
      RESULTS: Melancholic symptoms as assessed by one of the HamD24-based subscales
      directly correlated with overall improvement. Although ECT treatment was
      associated with greater improvement than was noted in non-ECT-treated patients,
      severity of melancholia ratings did not affect this relationship. Finally, both
      melancholia subscale scores followed approximately unimodal distributions.
      CONCLUSIONS: HamD24-based methods to assess severity of melancholic symptoms have
      limited clinical utility on an in-patient mood disorders unit in general, and for
      predicting ECT response in particular. Furthermore, these methods do not seem to
      identify bimodal populations of depressed patients (i.e. melancholic vs. non
      melancholic).

PMID- 25384954
TI  - Increased neuronal cell number in the dorsal motor nucleus of the vagus in
      schizophrenia.
AB  - Axer H, Bernstein H-G, Keiner S, Heronimus P, Sauer H, Witte OW, Bogerts B, Bar K
      J. Increased neuronal cell number in the dorsal motor nucleus of the vagus in
      schizophrenia. OBJECTIVE: Recently, a reduction in efferent vagal regulation has
      been found in schizophrenic patients. METHODS: Therefore, the brainstems of nine
      schizophrenic patients and nine normal controls were stereologically analysed.
      The number of neurons using the optical fractionator method and nuclear volumes
      applying the Cavalieri principle was estimated in Nissl stained sections of the
      dorsal motor nucleus of the vagus (DMNV) and the hypoglossal nucleus. RESULTS:
      The neurons in the right DMNV were significantly increased in the schizophrenic
      group compared to normal controls (p = 0.047), while the volumes of the DMNV did
      not differ. In contrast, no such differences were found in the hypoglossal
      nucleus. CONCLUSION: Although this pilot study is limited by its small sample
      size, the analysis of the solitarius-ambiguus-vagus system in schizophrenic
      patients is an interesting target in schizophrenia research. The most reasonable
      background for increased neuron numbers in the DMNV could be a system-specific
      neurodevelopmental disturbance in schizophrenia.

PMID- 25384955
TI  - Anesthesia in swine : optimizing a laboratory model to optimize translational
      research.
AB  - In order to extrapolate novel therapies from the bench to the bedside
      (translational research), animal experiments are scientifically necessary. Swine
      are popular laboratory animals as their cardiorespiratory physiology is very
      similar to humans. Every study has to be approved by the local and/or national
      animal ethical committees. As swine are extremely sensitive to stress the primary
      goal is therefore to provide a calm, stress-free environment in both housing and
      experimental facilities. Swine should be properly sedated for transport and
      normothermia needs to be ensured. It is recommended to commence anesthesia by
      injecting ketamine and propofol followed by endotracheal intubation during
      spontaneous breathing. After intubation, anesthesia maintenance is performed with
      morphine or piritramide, propofol and rocuronium and routine monitoring is
      applied analogue to a clinical operating theater for humans. Normothermia (38.5 
      degrees C) needs to be ensured. While surgical procedures can be readily
      extrapolated from a human operating theater to swine, non-anesthesiologist
      scientists may lose the animal rapidly due to airway management problems.
      Vascular access can be secured by cut-downs or ultrasound-guided techniques in
      the inguinal and the neck region. For humane euthanasia of pigs, morphine,
      followed by propofol, rocuronium and potassium chloride are recommended. As
      radical animal right groups may threaten scientists, it is prudent that animal
      laboratories have unmarked entrance doors, are located in buildings that are not
      accessible to the public and strictly controlled access of laboratory staff is
      enforced. In conclusion, swine are an excellent laboratory animal for bench to
      bedside research and can be managed properly when basic knowledge and adequate
      skills on careful handling, anesthesia and surgical considerations are present. 

PMID- 25384956
TI  - [Simulation as possible training for palliative emergencies: prospective initial
      data analysis of participants from two simulation training sessions].
AB  - BACKGROUND: Palliative emergencies describe an acute situation in patients with a
      life-limiting illness. At present defined curricula for prehospital emergency
      physician training for palliative emergencies are limited. Simulation-based
      training (SBT) for such palliative emergency situations is an exception both
      nationally and internationally. AIM: This article presents the preparation of
      recommendations in the training and development of palliative care emergency
      situations. MATERIAL AND METHODS: A selected literature search was performed
      using PubMed, EMBASE, Medline and the Cochrane database (1990-2013). Reference
      lists of included articles were checked by two reviewers. Data of the included
      articles were extracted, evaluated und summarized. In the second phase the
      participants of two simulated scenarios of palliative emergencies were asked to
      complete an anonymous 15-item questionnaire. The results of the literature search
      and the questionnaire-based investigation were compared and recommendations were
      formulated based on the results. RESULTS: Altogether 30 eligible national and
      international articles were included. Overall, training curricula in palliative
      emergencies are currently being developed nationally and internationally but are
      not yet widely integrated into emergency medical training and education. In the
      second part of the investigation, 25 participants (9 male, 16 female, 20
      physicians and 5 nurses) were included in 4 multiprofessional emergency medical
      simulation training sessions. The most important interests of the participants
      were the problems for training and further education concerning palliative
      emergencies described in the national and international literature. CONCLUSION:
      The literature review and the expectations of the participants underlined that
      the development and characteristics of palliative emergencies will become
      increasingly more important in outpatient emergency medicine. All participants
      considered palliative care to be very important concerning the competency for end
      of-life decisions in palliative patients. For this reason, special curricula and
      simulation for dealing with palliative care patients and special treatment
      decisions in emergency situations seem to be necessary.

PMID- 25384958
TI  - [Power of words].

PMID- 25384957
TI  - [Malignant hyperthermia].
AB  - Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy.
      Trigger substances, such as volatile anesthetic agents and the depolarizing
      muscle relaxant succinylcholine can induce a potentially fatal metabolic increase
      in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca)
      concentration. Mutations in the dihydropyridine ryanodine receptor complex in
      combination with the trigger substances are responsible for an uncontrolled
      release of Ca from the sarcoplasmic reticulum. This leads to activation of the
      contractile apparatus and a massive increase in cellular energy production.
      Exhaustion of the cellular energy reserves ultimately results in local muscle
      cell destruction and subsequent cardiovascular failure. The clinical picture of
      MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac
      arrhythmia whereas the body temperature rise, after which MH is named, often
      occurs later. Decisive for the course of MH episodes is a timely targeted
      therapy. Following introduction of the hydantoin derivative dantrolene, the
      previously high mortality of fulminant MH episodes could be reduced to well under
      10 %. An MH predisposition can be detected using the invasive in vitro
      contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures
      are in the developmental stage. 

PMID- 25384959
TI  - [Every year ...].

PMID- 25384960
TI  - Why genetic modification of lignin leads to low-recalcitrance biomass.
AB  - Genetic modification of plants via down-regulation of cinnamyl alcohol
      dehydrogenase leads to incorporation of aldehyde groups in the lignin polymer.
      The resulting lignocellulosic biomass has increased bioethanol yield. However, a
      molecular-scale explanation of this finding is currently lacking. Here, we
      perform molecular dynamics simulation of the copolymer with hemicellulose of wild
      type and the genetically modified lignin, in aqueous solution. We find that the
      non-covalent association with hemicellulose of lignin containing aldehyde groups
      is reduced compared to the wild-type. This phase separation may increase the cell
      wall porosity in the mutant plants, thus explaining their easier deconstruction
      to biofuels. The thermodynamic origin of the reduced lignin-hemicellulose
      association is found to be a more favorable self-interaction energy and less
      favorable interaction with hemicellulose for the mutant lignin. Furthermore,
      reduced hydration water density fluctuations are found for the mutant lignin,
      implying a more hydrophobic lignin surface. The results provide a detailed
      description of how aldehyde incorporation makes lignin more hydrophobic and
      reduces its association with hemicellulose, thus suggesting that increased lignin
      hydrophobicity may be an optimal characteristic required for improved biofuel
      production. 

PMID- 25384961
TI  - Development of food-grade nanoemulsions and emulsions for delivery of omega-3
      fatty acids: opportunities and obstacles in the food industry.
AB  - Consumption of biologically active amounts of omega-3 fatty acids is linked to
      improved human health, which has partly been attributed to their important role
      in brain development and cardiovascular health. Western diets are relatively low
      in omega-3 fatty acids and many consumers turn to supplements or functional foods
      to increase their intake of these healthy lipids. Fish oil is one of the most
      widely used sources of omega-3 fatty acid for supplementation and has greater
      health benefits than plant sources because of its higher concentration of
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The incorporation of
      omega-3 fatty acids into foods and beverages is often challenging due to their
      low water-solubility, poor oxidative stability, and variable bioavailability.
      Nanoemulsions offer a promising way to incorporate omega-3 fatty acids into
      liquid food systems like beverages, dressing, sauces, and dips. Nanoemulsions are
      colloidal dispersions that contain small oil droplets (r<100 nm) that may be able
      to overcome many of the challenges of fortifying foods and beverages with omega-3
      fatty acids. The composition and fabrication of nanoemulsions can be optimized to
      increase the chemical and physical stability of oil droplets, as well as to
      increase the bioavailability of omega-3 fatty acids.

PMID- 25384962
TI  - Mutant Enrichment with 3'-Modified Oligonucleotides (MEMO)-Quantitative PCR for
      Detection of NPM1 Mutations in Acute Myeloid Leukemia.
AB  - BACKGROUND: Detection of NPM1 mutations in acute myeloid leukemia (AML) is
      important for risk stratification, treatment decision, and therapeutic
      monitoring. We have designed a real-time PCR method implementing the Mutant
      enrichment with 3'-modified oligonucleotides (MEMO) technique to detect NPM1
      mutations and validated its utility in clinical samples. METHODS: Sensitivity and
      linearity were evaluated using serially diluted NPM1-positive samples. Clinical
      usefulness was assessed by measuring the levels of mutant alleles in 29 patients
      at diagnosis and in ten patients after induction chemotherapy. RESULTS: Excellent
      linear relationships between the mutant allele proportion and the threshold cycle
      (Ct) values (r = 0.999) were observed in a range of 1:1-1:10(3) . MEMO-PCR was
      able to detect NPM1 mutations regardless of mutant type and also detected novel
      mutants (964_967delTGGAinsATGATGTC, 957_959delCTGinsATGCATG, 960insTAAG, and
      960insTCAG). The concentrations of NPM1 mutant alleles decreased after induction
      chemotherapy in accordance with the reduction of tumor cells, and in one case,
      NPM1 mutant alleles were detectable about 7 months before morphological relapse.
      CONCLUSION: MEMO-quantitative PCR was shown to detect virtually all types of NPM1
      mutants with high sensitivity and specificity. This novel method may be useful in
      the diagnosis of AML with an NPM1 mutation, the detection of minimal residual
      disease, and the monitoring of treatment response.

PMID- 25384964
TI  - Cytokine profiling at disease onset: support for classification of young
      antinuclear antibody-positive patients as a separate category of juvenile
      idiopathic arthritis.

PMID- 25384963
TI  - Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic
      cancer.
AB  - Several recent studies have revealed that microRNAs (miRNAs) have a role in
      carcinogenesis and cancer development, and that it is stably detectable in
      plasma/serum. The aim of this study was to test whether miR-483-3p as well as miR
      21 could be plasma biomarkers for PDAC. The plasma samples were obtained from
      three groups including 32 pancreatic ductal adenocarcinoma (PDAC) patients, 12
      patients with intraductal papillary mucinous neoplasm (IPMN) patients and 30
      healthy controls (HC). We evaluated the plasma miR-483-3p and miR-21 expression
      level by quantitative RT-PCR. We compared the differences in the plasma level of
      these miRNAs among the three groups, and investigated the relevance of their
      plasma expression level to the clinical factors in PDAC. The expressions of miR
      483-3p and miR-21 were detected in all examined plasma samples. The plasma
      expression levels of these miRNAs were significantly higher in PDAC compared to
      HC (P<0.01). The plasma miR-483-3p expression was significantly higher in PDAC
      patients than IPMN patients (P<0.05). The plasma miR-21 level was associated with
      advanced stage (P<0.05), metastasis to lymph node and liver (P<0.01), and shorter
      survival (P<0.01) of the PDAC patients. Together, these findings suggest that
      measurement of the plasma miR-483-3p level is useful for discriminating PDAC from
      IPMN, and that the plasma miR-21 level predicts outcome of PDAC patients.

PMID- 25384965
TI  - Downregulation of miR-193b in systemic sclerosis regulates the proliferative
      vasculopathy by urokinase-type plasminogen activator expression.
AB  - OBJECTIVES: To investigate the role of microRNA-193b-3p (miR-193b) in the
      vascular pathophysiology of systemic sclerosis (SSc). METHODS: Expression of miR
      193b in skin biopsies and fibroblasts from patients with SSc and normal healthy
      (NH) controls were determined by real-time PCR. Transfection with miR-193b
      precursor and inhibitor were used to confirm targets of miR-193b. Proliferative
      effects of urokinase-type plasminogen activator (uPA) were determined by water
      soluble tetrazolium salt-1 assay and by analysis of proliferating cell nuclear
      antigen expression. Fluorescence activated cell sorting analysis was performed to
      investigate the effect of uPA on apoptosis. For inhibition of the uPA-cellular
      receptor for uPA (uPAR) pathway, uPAR neutralising antibodies and low molecular
      weight uPA were used. RESULTS: We found that miR-193b was downregulated in SSc
      fibroblasts and skin sections as compared with NH controls. The expression of miR
      193b was not affected by major profibrotic cytokines and hypoxia. Induction of
      miR-193b in SSc fibroblasts suppressed, and accordingly, knockdown of miR-193b
      increased the levels of messenger RNA and protein for uPA. uPA was found to be
      upregulated in SSc as compared with NH controls in a transforming growth factor
      beta dependent manner, and uPA was strongly expressed in vascular smooth muscle
      cells in SSc skin section. Interestingly, uPA induced cell proliferation and
      inhibited apoptosis of human pulmonary artery smooth muscle cells, and these
      effects were independent of uPAR signalling. CONCLUSIONS: In SSc, the
      downregulation of miR-193b induces the expression of uPA, which increases the
      number of vascular smooth muscle cells in an uPAR-independent manner and thereby
      contributes to the proliferative vasculopathy with intimal hyperplasia
      characteristic for SSc.

PMID- 25384966
TI  - Soluble P-selectin promotes acute myocardial infarction onset but not severity.
AB  - P-selectin, an integral membrane glycoprotein of platelets and endothelial cells,
      and the soluble form of P-selectin are hypothesized to play a role in the
      initiation of atherosclerosis and acute myocardial infarction (AMI). However,
      limited data are available with which to evaluate the main role of soluble P
      selectin (sP-selectin) in the onset or the severity of AMI. In the present study,
      we investigated 15 patients who suffered from angina, 10 patients who underwent
      percutaneous coronary intervention (PCI) therapy and 10 patients who underwent
      thrombolysis therapy, compared with 15 volunteers with no cardiovascular disease.
      We confirmed that the plasma sP-selectin levels were increased in patients with
      obesity (particularly pericardial obesity) and hyperlipidemia, positively
      correlated with plasma tumor necrosis factor (TNF)-alpha and strongly negatively
      correlated with adiponectin in all patients regardless of AMI status.
      Furthermore, sP-selectin levels were significantly higher in PCI and thrombolysis
      patients compared with angina patients and the control cohort. However, we
      observed that sP-selectin levels did not change following PCI and thrombolysis
      therapy. In addition, there was no correlation between sP-selectin levels and the
      severity of AMI in the cohort which received PCI or thrombolysis therapy.
      Therefore, we deduced that sP-selectin only induced the onset of AMI but did not
      promote its severity. To confirm this hypothesis, a P-selectin inhibitor was
      administered to an atherosclerosis formation model, plaque rapture model and
      neointimal hyperplasia model. We revealed that atherosclerotic plaque formation
      and rupture, neointimal formation and neointimal bleeding were suppressed by the
      sP-selectin inhibitor. We concluded that sP-selectin, induced by systemic
      inflammation in conditions including obesity and hyperlipidemia, promoted
      atherosclerotic plaque and neointimal formation, plaque rapture and neointimal
      bleeding, further leading to AMI. We also demonstrated that sP-selectin had no
      effect on the severity of AMI.

PMID- 25384967
TI  - Electric field manipulation of magnetic and transport properties in
      SrRuO3/Pb(Mg1/3Nb2/3)O3-PbTiO3 heterostructure.
AB  - The electric field manipulation of magnetic properties is currently of great
      interest for the opportunities provided in low-energy-consuming spintronics
      devices. Here, we report the effect of electric field on magnetic and transport
      properties of the ferromagnetic SrRuO(3) film which is epitaxially grown on
      Pb(Mg(1/3)Nb(2/3))O3-PbTiO(3) ferroelectric substrate. With the application of
      electric field on the substrate, the magnetization, Curie temperature and
      resistivity of SrRuO(3) are effectively modified. The mechanism of the electric
      field manipulation of these properties is ascribed to the rotations of RuO6
      oxygen octahedra caused by the electric-field-induced strain, which changes the
      overlap and hybridization between the Ru 4d orbitals and O 2p orbitals, resulting
      in the modification of the magnetic and electronic properties.

PMID- 25384968
TI  - Angled transscleral intravitreal injection: a crossover study.
AB  - PURPOSE: The perfect intravitreal injection delivers an exact amount of
      medication with the least risk to vision and the eye. We examined 2 different
      methods of intravitreal injection to determine if an angled transscleral entry
      for intravitreal injection results in less egress of intravitreal contents,
      including medication. METHODS: In a crossover controlled trial at an outpatient
      clinical facility within a major ophthalmology referral center, we treated 10
      patients. The surgical technique involved injecting 0.05 mL of bevacizumab
      injected in one eye by both an orthogonal (straight in) and oblique (angled)
      technique. The intraocular pressure (IOP) was measured immediately before and
      after each monthly injection. RESULTS: Orthogonal injections raised the IOP
      significantly less (mean 24.6 mm Hg or 126%) than oblique injections (29.6 mm Hg
      or 152%) (p = 0.045). There were no reported differences in injection-related
      pain or adverse effects between the techniques. CONCLUSIONS: Oblique or angled
      injections caused a larger IOP rise than straight or orthogonal injections. This
      finding suggests that oblique injections are self-sealing, deliver a higher dose
      of medication, or prevent vitreous reflux as well as close a potential portal of
      entry for pathogens.

PMID- 25384969
TI  - Dome-shaped macula associated with Best vitelliform macular dystrophy.
AB  - PURPOSE: Dome-shaped macula (DSM) has been described recently as an inward
      convexity of the macula typical of myopic eyes detectable on spectral-domain
      optical coherence tomography (SD-OCT). The authors describe a case of monolateral
      DSM associated with Best vitelliform macular dystrophy (VMD). METHODS: Case
      report. RESULTS: A 60-year-old man already diagnosed with VMD in vitelliruptive
      stage underwent SD-OCT that revealed the typical vitelliform material
      accumulation associated in the left eye with a convex elevation of the macula. No
      change was registered over a 1-year follow-up. CONCLUSIONS: This is the first
      report describing a monolateral DSM associated with VMD. Dome-shaped macula could
      be considered as a nonspecific scleral alteration, probably due to increased
      scleral thickness, which can accompany many retinal disorders.

PMID- 25384970
TI  - Conjunctival epithelial cells cultivated ex vivo from patients with total limbal
      stem cell deficiency.
AB  - PURPOSE: Reconstruction of the ocular surface is challenging. As an alternative
      to mucosal and limbal epithelial, we study the feasibility of cultivated human
      conjunctival epithelial (HCjE) cells of patients with total limbal stem cell
      deficiency (LSCD). METHODS: We studied superior forniceal conjunctival biopsies
      harvested from 9 living donors with total LSCD of several etiologies who
      underwent surgery for ocular surface reconstruction. The conjunctival explants
      were cultivated on serum and growth factor supplemented DMEM/F12 under submerged
      conditions on denuded human amniotic membrane and tissue culture dishes. The area
      of cell growth was assessed. Cell morphology was analyzed by light microscopy,
      impression cytology, and transmission electron microscopy. Cultures were
      evaluated for epithelial cytokeratins (CK3, CK19), proliferation marker (Ki-67),
      and putative stem cells markers (ABCG2 and p63). Confocal immunofluorescence was
      also performed to assess CK3, CK19, Ki-67, ABCG2, and p63. RESULTS: The HCjE
      cells cultivated ex vivo were successfully expanded on denuded amniotic membrane
      but with a slower growth than in the tissue culture dish. Transmission electron
      microscopy showed stratified epithelium with microvilli, desmosomes, and
      hemidesmosomes. Impression cytology showed PAS+ cells that resembled goblet
      cells. Immunocytochemical analysis showed positivity for CK3, CK19, Ki-67, ABCG2,
      and p63. Confocal immunofluorescence was positive for CK3, CK19, Ki-67, ABCG2,
      and p63. CONCLUSIONS: Our results showed that it is possible to cultivate HCjE
      cells ex vivo of patients with ocular surface diseases. This method is important
      for ocular surface reconstruction in patients with bilateral total LSCD.

PMID- 25384971
TI  - A protease-independent function for SPPL3 in NFAT activation.
AB  - The signal peptide peptidase (SPP)-related intramembrane aspartyl proteases are a
      homologous group of polytopic membrane proteins, some of which function in innate
      or adaptive immunity by cleaving proteins involved in antigen presentation or
      intracellular signaling. Signal peptide peptidase-like 3 (SPPL3) is a poorly
      characterized endoplasmic reticulum (ER)-localized member of this family, with no
      validated cellular substrates. We report here the isolation of SPPL3 in a screen
      for activators of NFAT, a transcription factor that controls lymphocyte
      development and function. We find that SPPL3 is required downstream of T cell
      receptor engagement for maximal Ca(2+) influx and NFAT activation. Surprisingly,
      the proteolytic activity of SPPL3 is not required for its role in this pathway.
      SPPL3 enhances the signal-induced association of stromal interaction molecule 1
      (STIM1) and Orai1 and is even required for the full activity of constitutively
      active STIM1 variants that bind Orai1 independently of ER Ca(2+) release. SPPL3
      associates with STIM1 through at least two independent domains, the transmembrane
      region and the CRAC activation domain (CAD), and can promote the association of
      the STIM1 CAD with Orai1. Our results assign a function in lymphocyte signaling
      to SPPL3 and highlight the emerging importance of nonproteolytic functions for
      members of the intramembrane aspartyl protease family. 

PMID- 25384972
TI  - Human monocyte recognition of adenosine-based cyclic dinucleotides unveils the
      A2a Galphas protein-coupled receptor tonic inhibition of mitochondrially induced
      cell death.
AB  - Cyclic dinucleotides are important messengers for bacteria and protozoa and are
      well-characterized immunity alarmins for infected mammalian cells through
      intracellular binding to STING receptors. We sought to investigate their unknown
      extracellular effects by adding cyclic dinucleotides to the culture medium of
      freshly isolated human blood cells in vitro. Here we report that adenosine
      containing cyclic dinucleotides induce the selective apoptosis of monocytes
      through a novel apoptotic pathway. We demonstrate that these compounds are
      inverse agonist ligands of A2a, a Galphas-coupled adenosine receptor selectively
      expressed by monocytes. Inhibition of monocyte A2a by these ligands induces
      apoptosis through a mechanism independent of that of the STING receptors. The
      blockade of basal (adenosine-free) signaling from A2a inhibits protein kinase A
      (PKA) activity, thereby recruiting cytosolic p53, which opens the mitochondrial
      permeability transition pore and impairs mitochondrial respiration, resulting in
      apoptosis. A2a antagonists and inverse agonist ligands induce apoptosis of human
      monocytes, while A2a agonists are antiapoptotic. In vivo, we used a mock
      developing human hematopoietic system through NSG mice transplanted with human
      CD34(+) cells. Treatment with cyclic di-AMP selectively depleted A2a-expressing
      monocytes and their precursors via apoptosis. Thus, monocyte recognition of
      cyclic dinucleotides unravels a novel proapoptotic pathway: the A2a Galphas
      protein-coupled receptor (GPCR)-driven tonic inhibitory signaling of
      mitochondrion-induced cell death. 

PMID- 25384974
TI  - Protein O-fucosyltransferase 1 expression impacts myogenic C2C12 cell commitment
      via the Notch signaling pathway.
AB  - The Notch signaling pathway plays a crucial role in skeletal muscle regeneration
      in mammals by controlling the transition of satellite cells from quiescence to an
      activated state, their proliferation, and their commitment toward myotubes or
      self-renewal. O-fucosylation on Notch receptor epidermal growth factor (EGF)-like
      repeats is catalyzed by the protein O-fucosyltransferase 1 (Pofut1) and primarily
      controls Notch interaction with its ligands. To approach the role of O
      fucosylation in myogenesis, we analyzed a murine myoblastic C2C12 cell line
      downregulated for Pofut1 expression by short hairpin RNA (shRNA) inhibition
      during the time course of differentiation. Knockdown of Pofut1 affected the
      signaling pathway activation by a reduction of the amount of cleaved Notch
      intracellular domain and a decrease in downstream Notch target gene expression.
      Depletion in Pax7(+)/MyoD(-) cells and earlier myogenic program entrance were
      observed, leading to an increase in myotube quantity with a small number of
      nuclei, reflecting fusion defects. The rescue of Pofut1 expression in knockdown
      cells restored Notch signaling activation and a normal course in C2C12
      differentiation. Our results establish the critical role of Pofut1 on Notch
      pathway activation during myogenic differentiation. 

PMID- 25384973
TI  - Cdc42p-interacting protein Bem4p regulates the filamentous-growth mitogen
      activated protein kinase pathway.
AB  - The ubiquitous Rho (Ras homology) GTPase Cdc42p can function in different
      settings to regulate cell polarity and cellular signaling. How Cdc42p and other
      proteins are directed to function in a particular context remains unclear. We
      show that the Cdc42p-interacting protein Bem4p regulates the mitogen-activated
      protein kinase (MAPK) pathway that controls filamentous growth in Saccharomyces
      cerevisiae. Bem4p controlled the filamentous-growth pathway but not other MAPK
      pathways (mating or high-osmolarity glycerol response [HOG]) that also require
      Cdc42p and other shared components. Bem4p associated with the plasma membrane
      (PM) protein, Sho1p, to regulate MAPK activity and cell polarization under
      nutrient-limiting conditions that favor filamentous growth. Bem4p also interacted
      with the major activator of Cdc42p, the guanine nucleotide exchange factor (GEF)
      Cdc24p, which we show also regulates the filamentous-growth pathway. Bem4p
      interacted with the pleckstrin homology (PH) domain of Cdc24p, which functions in
      an autoinhibitory capacity, and was required, along with other pathway
      regulators, to maintain Cdc24p at polarized sites during filamentous growth.
      Bem4p also interacted with the MAPK kinase kinase (MAPKKK) Ste11p. Thus, Bem4p is
      a new regulator of the filamentous-growth MAPK pathway and binds to general
      proteins, like Cdc42p and Ste11p, to promote a pathway-specific response. 

PMID- 25384975
TI  - RAD6 promotes homologous recombination repair by activating the autophagy
      mediated degradation of heterochromatin protein HP1.
AB  - Efficient DNA double-strand break (DSB) repair is critical for the maintenance of
      genome stability. Unrepaired or misrepaired DSBs cause chromosomal rearrangements
      that can result in severe consequences, such as tumorigenesis. RAD6 is an E2
      ubiquitin-conjugating enzyme that plays a pivotal role in repairing UV-induced
      DNA damage. Here, we present evidence that RAD6 is also required for DNA DSB
      repair via homologous recombination (HR) by specifically regulating the
      degradation of heterochromatin protein 1alpha (HP1alpha). Our study indicates
      that RAD6 physically interacts with HP1alpha and ubiquitinates HP1alpha at
      residue K154, thereby promoting HP1alpha degradation through the autophagy
      pathway and eventually leading to an open chromatin structure that facilitates
      efficient HR DSB repair. Furthermore, bioinformatics studies have indicated that
      the expression of RAD6 and HP1alpha exhibits an inverse relationship and
      correlates with the survival rate of patients. 

PMID- 25384976
TI  - Cyclin-dependent kinase 12 increases 3' end processing of growth factor-induced c
      FOS transcripts.
AB  - Transcriptional cyclin-dependent kinases (CDKs) regulate RNA polymerase II
      initiation and elongation as well as cotranscriptional mRNA processing. In this
      report, we describe an important role for CDK12 in the epidermal growth factor
      (EGF)-induced c-FOS proto-oncogene expression in mammalian cells. This kinase was
      found in the exon junction complexes (EJC) together with SR proteins and was thus
      recruited to RNA polymerase II. In cells depleted of CDK12 or eukaryotic
      translation initiation factor 4A3 (eIF4A3) from the EJC, EGF induced fewer c-FOS
      transcripts. In these cells, phosphorylation of serines at position 2 in the C
      terminal domain (CTD) of RNA polymerase II, as well as levels of cleavage
      stimulating factor 64 (Cstf64) and 73-kDa subunit of cleavage and polyadenylation
      specificity factor (CPSF73), was reduced at the c-FOS gene. These effects
      impaired 3' end processing of c-FOS transcripts. Mutant CDK12 proteins lacking
      their Arg-Ser-rich (RS) domain or just the RS domain alone acted as dominant
      negative proteins. Thus, CDK12 plays an important role in cotranscriptional
      processing of c-FOS transcripts. 

PMID- 25384977
TI  - Heat stress-induced Cup9-dependent transcriptional regulation of SIR2.
AB  - The epigenetic writer Sir2 maintains the heterochromatin state of chromosome in
      three chromosomal regions, namely, the silent mating type loci, telomeres, and
      the ribosomal DNA (rDNA). In this study, we demonstrated the mechanism by which
      Sir2 is regulated under heat stress. Our study reveals that a transient heat
      shock causes a drastic reduction in the SIR2 transcript which results in
      sustained failure to initiate silencing for as long as 90 generations. Hsp82
      overexpression, which is the usual outcome of heat shock treatment, leads to a
      similar downregulation of SIR2 transcription. Using a series of genetic
      experiments, we have established that heat shock or Hsp82 overexpression causes
      upregulation of CUP9 that, in turn, represses SIR2 transcription by binding to
      its upstream activator sequence. We have mapped the cis regulatory element of
      SIR2. Our study shows that the deletion of cup9 causes reversal of the Hsp82
      overexpression phenotype and upregulation of SIR2 expression in heat-induced
      Hsp82-overexpressing cells. On the other hand, we found that Cup9 overexpression
      represses SIR2 transcription and leads to a failure in the establishment of
      heterochromatin. The results of our study highlight the mechanism by which
      environmental factors amend the epigenetic configuration of chromatin. 

PMID- 25384978
TI  - Targeted identification of sialoglycoproteins in hypoxic endothelial cells and
      validation in zebrafish reveal roles for proteins in angiogenesis.
AB  - The formation of new vessels in the tumor, termed angiogenesis, is essential for
      primary tumor growth and facilitates tumor invasion and metastasis. Hypoxia has
      been described as one trigger of angiogenesis. Indeed, hypoxia, which is
      characterized by areas of low oxygen levels, is a hallmark of solid tumors
      arising from an imbalance between oxygen delivery and consumption. Hypoxic
      conditions have profound effects on the different components of the tumoral
      environment. For example, hypoxia is able to activate endothelial cells, leading
      to angiogenesis but also thereby initiating a cascade of reactions involving
      neutrophils, smooth muscle cells, and fibroblasts. In addition, hypoxia directly
      regulates the expression of many genes for which the role and the importance in
      the tumoral environment remain to be completely elucidated. In this study, we
      used a method to selectively label sialoglycoproteins to identify new membrane
      and secreted proteins involved in the adaptative process of endothelial cells by
      mass spectrometry-based proteomics. We used an in vitro assay under hypoxic
      condition to observe an increase of protein expression or modifications of
      glycosylation. Then the function of the identified proteins was assessed in a
      vasculogenesis assay in vivo by using a morpholino strategy in zebrafish. First,
      our approach was validated by the identification of sialoglycoproteins such as
      CD105, neuropilin-1, and CLEC14A, which have already been described as playing
      key roles in angiogenesis. Second, we identified several new proteins regulated
      by hypoxia and demonstrated for the first time the pivotal role of GLUT-1,
      TMEM16F, and SDF4 in angiogenesis. 

PMID- 25384979
TI  - Discovery of Mycobacterium tuberculosis alpha-1,4-glucan branching enzyme (GlgB)
      inhibitors by structure- and ligand-based virtual screening.
AB  - GlgB (alpha-1,4-glucan branching enzyme) is the key enzyme involved in the
      biosynthesis of alpha-glucan, which plays a significant role in the virulence and
      pathogenesis of Mycobacterium tuberculosis. Because alpha-glucans are implicated
      in the survival of both replicating and non-replicating bacteria, there exists an
      exigent need for the identification and development of novel inhibitors for
      targeting enzymes, such as GlgB, involved in this pathway. We have used the
      existing structural information of M. tuberculosis GlgB for high throughput
      virtual screening and molecular docking. A diverse database of 330,000 molecules
      was used for identifying novel and efficacious therapeutic agents for targeting
      GlgB. We also used three-dimensional shape as well as two-dimensional similarity
      matrix methods to identify diverse molecular scaffolds that inhibit M.
      tuberculosis GlgB activity. Virtual hits were generated after structure and
      ligand-based screening followed by filters based on interaction with human GlgB
      and in silico pharmacokinetic parameters. These hits were experimentally
      evaluated and resulted in the discovery of a number of structurally diverse
      chemical scaffolds that target M. tuberculosis GlgB. Although a number of
      inhibitors demonstrated in vitro enzyme inhibition, two compounds in particular
      showed excellent inhibition of in vivo M. tuberculosis survival and its ability
      to get phagocytosed. This work shows that in silico docking and three-dimensional
      chemical similarity could be an important therapeutic approach for developing
      inhibitors to specifically target the M. tuberculosis GlgB enzyme. 

PMID- 25384980
TI  - Molecular clock regulates daily alpha1-2-fucosylation of the neural cell adhesion
      molecule (NCAM) within mouse secondary olfactory neurons.
AB  - The circadian clock regulates various behavioral and physiological rhythms in
      mammals. Circadian changes in olfactory functions such as neuronal firing in the
      olfactory bulb (OB) and olfactory sensitivity have recently been identified,
      although the underlying molecular mechanisms remain unknown. We analyzed the
      temporal profiles of glycan structures in the mouse OB using a high-density
      microarray that includes 96 lectins, because glycoconjugates play important roles
      in the nervous system such as neurite outgrowth and synaptogenesis. Sixteen
      lectin signals significantly fluctuated in the OB, and the intensity of all three
      that had high affinity for alpha1-2-fucose (alpha1-2Fuc) glycan in the microarray
      was higher during the nighttime. Histochemical analysis revealed that alpha1-2Fuc
      glycan is located in a diurnal manner in the lateral olfactory tract that
      comprises axon bundles of secondary olfactory neurons. The amount of alpha1-2Fuc
      glycan associated with the major target glycoprotein neural cell adhesion
      molecule (NCAM) varied in a diurnal fashion, although the mRNA and protein
      expression of Ncam1 did not. The mRNA and protein expression of Fut1, a alpha1-2
      specific fucosyltransferase gene, was diurnal in the OB. Daily fluctuation of the
      alpha1-2Fuc glycan was obviously damped in homozygous Clock mutant mice with
      disrupted diurnal Fut1 expression, suggesting that the molecular clock governs
      rhythmic alpha1-2-fucosylation in secondary olfactory neurons. These findings
      suggest the possibility that the molecular clock is involved in the diurnal
      regulation of olfaction via alpha1-2-fucosylation in the olfactory system. 

PMID- 25384981
TI  - Activation of 3-phosphoinositide-dependent kinase 1 (PDK1) and serum- and
      glucocorticoid-induced protein kinase 1 (SGK1) by short-chain sphingolipid C4
      ceramide rescues the trafficking defect of DeltaF508-cystic fibrosis
      transmembrane conductance regulator (DeltaF508-CFTR).
AB  - Cystic fibrosis (CF) is due to a folding defect in the CF transmembrane
      conductance regulator (CFTR) protein. The most common mutation, DeltaF508,
      prevents CFTR from trafficking to the apical plasma membrane. Here we show that
      activation of the PDK1/SGK1 signaling pathway with C4-ceramide (C4-CER), a non
      toxic small molecule, functionally corrects the trafficking defect in both
      cultured CF cells and primary epithelial cell explants from CF patients. The
      mechanism of C4-CER action involves a series of mutual autophosphorylation and
      phosphorylation events between PDK1 and SGK1. Detailed mechanistic studies
      indicate that C4-CER initially induces autophosphorylation of SGK1 at Ser(422).
      SGK1[Ser(P)(422)] and C4-CER coincidently bind PDK1 and permit PDK1 to
      autophosphorylate at Ser(241). Then PDK1[Ser(P)(241)] phosphorylates
      SGK1[Ser(P)(422)] at Thr(256) to generate fully activated SGK1[Ser(422),
      Thr(P)(256)]. SGK1[Ser(P)(422),Thr(P)(256)] phosphorylates and inactivates the E3
      ubiquitin ligase Nedd4-2. DeltaF508-CFTR is thus free to traffic to the plasma
      membrane. Importantly, C4-CER-mediated activation of both PDK1 and SGK1 is
      independent of the PI3K/Akt/mammalian target of rapamycin signaling pathway.
      Physiologically, C4-CER significantly increases maturation and stability of
      DeltaF508-CFTR (t1/2 ~10 h), enhances cAMP-activated chloride secretion, and
      suppresses hypersecretion of interleukin-8 (IL-8). We suggest that candidate
      drugs for CF directed against the PDK1/SGK1 signaling pathway, such as C4-CER,
      provide a novel therapeutic strategy for a life-limiting disorder that affects
      one child, on average, each day. 

PMID- 25384982
TI  - Human CHD2 is a chromatin assembly ATPase regulated by its chromo- and DNA
      binding domains.
AB  - Chromodomain helicase DNA-binding protein 2 (CHD2) is an ATPase and a member of
      the SNF2-like family of helicase-related enzymes. Although deletions of CHD2 have
      been linked to developmental defects in mice and epileptic disorders in humans,
      little is known about its biochemical and cellular activities. In this study, we
      investigate the ATP-dependent activity of CHD2 and show that CHD2 catalyzes the
      assembly of chromatin into periodic arrays. We also show that the N-terminal
      region of CHD2, which contains tandem chromodomains, serves an auto-inhibitory
      role in both the DNA-binding and ATPase activities of CHD2. While loss of the N
      terminal region leads to enhanced chromatin-stimulated ATPase activity, the N
      terminal region is required for ATP-dependent chromatin remodeling by CHD2. In
      contrast, the C-terminal region, which contains a putative DNA-binding domain,
      selectively senses double-stranded DNA of at least 40 base pairs in length and
      enhances the ATPase and chromatin remodeling activities of CHD2. Our study shows
      that the accessory domains of CHD2 play central roles in both regulating the
      ATPase domain and conferring selectivity to chromatin substrates. 

PMID- 25384983
TI  - Carbon monoxide (CO) is a novel inhibitor of connexin hemichannels.
AB  - Hemichannels (HCs) are hexamers of connexins that can form gap-junction channels
      at points of cell contacts or "free HCs" at non-contacting regions. HCs are
      involved in paracrine and autocrine cell signaling, and under pathological
      conditions may induce and/or accelerate cell death. Therefore, studies of HC
      regulation are of great significance. Nitric oxide affects the activity of Cx43
      and Cx46 HCs, whereas carbon monoxide (CO), another gaseous transmitter,
      modulates the activity of several ion channels, but its effect on HCs has not
      been explored. We studied the effect of CO donors (CORMs) on Cx46 HCs expressed
      in Xenopus laevis oocytes using two-electrode voltage clamp and on Cx43 and Cx46
      expressed in HeLa cells using a dye-uptake technique. CORM-2 inhibited Cx46 HC
      currents in a concentration-dependent manner. The C-terminal domain and
      intracellular Cys were not necessary for the inhibition. The effect of CORM-2 was
      not prevented by guanylyl-cyclase, protein kinase G, or thioredoxin inhibitors,
      and was not due to endocytosis of HCs. However, the effect of CORM-2 was reversed
      by reducing agents that act extracellularly. Additionally, CO inhibited dye
      uptake of HeLa cells expressing Cx43 or Cx46, and MCF-7 cells, which endogenously
      express Cx43 and Cx46. Because CORM-2 carbonylates Cx46 in vitro and induces
      conformational changes, a direct effect of that CO on Cx46 is possible. The
      inhibition of HCs could help to understand some of the biological actions of CO
      in physiological and pathological conditions. 

PMID- 25384984
TI  - Amino acid residues 489-503 of dihydropyridine receptor (DHPR) beta1a subunit are
      critical for structural communication between the skeletal muscle DHPR complex
      and type 1 ryanodine receptor.
AB  - The beta1a subunit is a cytoplasmic component of the dihydropyridine receptor
      (DHPR) complex that plays an essential role in skeletal muscle excitation
      contraction (EC) coupling. Here we investigate the role of the C-terminal end of
      this auxiliary subunit in the functional and structural communication between the
      DHPR and the Ca(2+) release channel (RyR1). Progressive truncation of the beta1a
      C terminus showed that deletion of amino acid residues Gln(489) to Trp(503)
      resulted in a loss of depolarization-induced Ca(2+) release, a severe reduction
      of L-type Ca(2+) currents, and a lack of tetrad formation as evaluated by freeze
      fracture analysis. However, deletion of this domain did not affect
      expression/targeting or density (Qmax) of the DHPR-alpha1S subunit to the plasma
      membrane. Within this motif, triple alanine substitution of residues Leu(496),
      Leu(500), and Trp(503), which are thought to mediate direct beta1a-RyR1
      interactions, weakened EC coupling but did not replicate the truncated phenotype.
      Therefore, these data demonstrate that an amino acid segment encompassing
      sequence (489)QVQVLTSLRRNLSFW(503) of beta1a contains critical determinant(s) for
      the physical link of DHPR and RyR1, further confirming a direct correspondence
      between DHPR positioning and DHPR/RyR functional interactions. In addition, our
      data strongly suggest that the motif Leu(496)-Leu(500)-Trp(503) within the beta1a
      C-terminal tail plays a nonessential role in the bidirectional DHPR/RyR1
      signaling that supports skeletal-type EC coupling. 

PMID- 25384985
TI  - Temporal effect of depressive symptoms on the longitudinal evolution of
      rheumatoid arthritis disease activity.
AB  - OBJECTIVE: Depression is common in the rheumatoid arthritis (RA) population, yet
      little is known of its effect on the course of disease activity. The aim of our
      study was to determine if prevalent and incident depressive symptoms influenced
      longitudinal changes in RA disease activity. METHODS: RA patients with and
      without depressive symptoms were identified using single-item questions from an
      existing registry sample. Mixed-effects models were used to examine changes in
      disease activity over 2 years in those with and without prevalent and incident
      depressive symptoms. Outcome variables included composite disease activity, joint
      counts, global assessments, pain, function, and acute-phase reactants. Model
      based outcome estimations at the index dates and corresponding 1- and 2-year
      changes were calculated. RESULTS: Rates of disease activity change were
      significantly different in patients with a lifetime prevalence of symptomology,
      but not incident depressive symptoms, when compared to controls. Prior symptoms
      were associated with slower rates of disease activity decline, evidenced by the
      estimated 1-year Clinical Disease Activity Index changes: -3.0 (-3.3, -2.6) and 
      4.0 (-4.3, -3.6) in patients with and without lifetime prevalence, respectively.
      Analogous results were obtained for most of the other disease activity outcomes;
      although, there was no temporal effect of prevalent symptoms of depression on
      swollen joints and acute-phase reactants. CONCLUSION: Depressive symptoms
      temporally influence the evolution of RA disease activity, and the magnitude is
      dependent on the time of symptomatic onset. However, the effect is limited to
      patient-reported pain, global assessment, and function, as well as physician
      reported global assessment and tender joints.

PMID- 25384986
TI  - Visualisation of the intact dura mater and brain surface in infant autopsies: a
      minimally destructive technique for the post-mortem assessment of head injury.
AB  - During the post-mortem examination of babies and young children, it is important
      to be able to visualise the brain and its coverings, particularly in cases where
      a head injury is likely to have occurred. In this paper, we present an improved
      method for removal of the calvarial bones in infant autopsies to enable viewing
      of the dura mater and brain. In contrast to the standard post-mortem procedure
      for observing and removing the brain, this novel technique is minimally
      disruptive, allowing the dura mater to remain undamaged. Specialised paediatric
      neurosurgical tools were used to remove the skull bones from 23 neonates, infants
      and young children during post-mortem examination. In 21 of our 23 cases, the
      calvarial bones were removed successfully with the dura mater remaining intact.
      In one case, there was a thickening of the dura mater which created a strong
      adherence of this membrane to the bone. In another case, the dura mater was
      slightly damaged due to the inexperience of the operator in using the
      neurosurgical tools. This method of calvarial bone removal reduces the degree of
      post-mortem artefact and enhances the ability to observe and photographically
      document autopsy findings, including the artefact-free detection of signs of
      injury such as epidural or subdural haematoma, and brain swelling. This technique
      has now become a routine practise in both of our units to remove the skull bones
      in infant/young children post-mortem examinations. 

PMID- 25384987
TI  - Age estimation in children and young adolescents for forensic purposes using
      fourth cervical vertebra (C4).
AB  - The aim of this study was to evaluate the applicability of using the growth of
      the body of C4 vertebra for the estimation of age in children and young
      adolescents. We used the fact that the proportions between the radiologic
      projections of the posterior and anterior sides of the C4 vertebral body, which
      forms a trapezoidal shape, differ with age: in younger individuals, the posterior
      side is higher, whereas in older individuals, the projections of the sides of the
      vertebral body form a rectangular shape with the two sides equal or with the
      anterior side slightly higher. Cephalograms of 444 Italian subjects (214 female
      and 230 male individuals) aged between 5 and 15 years and with no obvious
      development abnormalities were analyzed. The projections of the anterior side (a)
      and of the posterior side (b) of each C4 body were measured, and their ratio
      (Vba), as a value of the C4 body development, was used for age estimation.
      Distribution of the Vba suggested that it does not change after 13 years in
      female and 14 years in male subjects. Consequently, we restricted our analysis of
      the Vba growing model until 14 years in both sexes. We used a Bayesian
      calibration method to estimate chronological age as function of Vba as a
      predicting variable. The intra- and inter-observer agreement was satisfactory,
      using intra-class correlation coefficient of Vba on 30 randomly selected
      cephalograms. The mean absolute errors were 1.34 years (standard deviation 0.95)
      and 1.01 years (standard deviation 0.71), and the mean inter-quartile ranges of
      the calibrating distribution were 2.32 years (standard deviation 0.25) in male
      and 1.72 years (standard deviation 0.39) in female individuals, respectively. The
      slopes of the regression of the estimated age error to chronological age were
      0.02 in male and 0.06 in female individuals, where both values did not result
      significantly different from 0 (p > 0.12). In conclusion, although our Bayesian
      calibration method might not really outperform the classical regression models in
      the precision of its estimates, it appears to be more robust, to greatly reduce
      the typical bias inherent in the regression model approach, and to have the
      ability to incorporate multiple predictors. 

PMID- 25384988
TI  - Online background cleanup followed by high-performance liquid chromatography with
      tandem mass spectrometry for the analysis of perfluorinated compounds in human
      blood.
AB  - In this study, a novel method for the analysis of perfluorinated compounds in
      whole blood has been developed and validated. The method was developed by using a
      conventional reversed-phase C18 column as a trapping column for the elimination
      of background contamination and high-performance liquid chromatography with
      tandem mass spectrometry for the target compounds analysis. The trapping column
      provided fast online separation of the background contamination of perfluorinated
      compounds. In this developed method, the limits of detection for different
      perfluorinated compounds ranged from 0.06 to 0.14 ng/mL. It is notable that the
      limit of detection (0.07 ng/mL) for perfluorooctanoic acid was improved
      significantly after the elimination of background contamination. The method was
      also validated in terms of sensitivity, accuracy, and precision. The recoveries
      ranged from 66.8 to 111.9%, with relative standard deviations from 2.1 to 15.3%.
      Our preliminary data suggest that the novel method based on trapping column
      cleanup followed by high-performance liquid chromatography with tandem mass
      spectrometry could be applied in studies on the human exposure to perfluorinated
      compounds. 

PMID- 25384989
TI  - Discontinued drugs in 2012 - 2013: hepatitis C virus infection.
AB  - INTRODUCTION: Hepatitis C virus (HCV) chronically infects about 150 million
      people worldwide. Antiviral treatment can stop and even reverse the progression
      of the disease. Several antivirals have been developed. However, about 10,000
      compounds are tested for each drug that eventually reaches the market. It would
      be useful to learn from these failures, for example, by reporting the candidate
      drugs that were discontinued and the reason for discontinuation. AREAS COVERED:
      This article focuses on the anti-HCV drug candidates discontinued between 1
      January 2012 and 1 January 2014. EXPERT OPINION: In detail, 17 drugs were
      discontinued. Of these: 10 were NS5B inhibitors, 3 were NS5A inhibitors, 2 were
      immunostimulants, 1 was a therapeutic and prophylactic vaccine and 1 an NS3
      inhibitor. Only 3 candidates were discontinued in the preclinical phase, and 14
      were discontinued during clinical development (8 in Phase II and 6 in Phase I).
      Most discontinuations were attributed to corporate strategic decisions. The
      authors believe that learning from HCV drug development failures will help
      pharmaceutical companies and researchers to develop better strategies for the
      future. It is therefore important that this information is made available.

PMID- 25384990
TI  - Prevalence, incidence and clinical impact of cachexia: facts and numbers-update
      2014.
AB  - Cachexia is a serious but underrecognised consequence of many chronic diseases.
      Its prevalence ranges from 5-15 % in end-stage chronic heart failure to 50-80 %
      in advanced cancer. Cachexia is also part of the terminal course of many patients
      with chronic kidney disease, chronic obstructive pulmonary disease (COPD) and
      rheumatoid arthritis. Mortality rates of patients with cachexia range from 10-15
      % per year in COPD through 20-30 % per year in chronic heart failure and chronic
      kidney disease to 80 % in cancer. The condition is also associated with poor
      quality of life. In the industrialised world, the overall prevalence of cachexia
      (due to any disease and not necessarily associated with hospital admission) is
      growing and it currently affects around 1 % of the patient population, i.e.
      around 9 million people. It is also a significant health problem in other parts
      of the globe. Recently there have been advances in our understanding of the
      multifactorial nature of the condition, and particularly of the role of
      inflammatory mediators and the imbalance of anabolism and catabolism. Several
      promising approaches to treatment have failed to live up to the challenge of
      phase III clinical trials, but the ghrelin receptor agonist anamorelin seems to
      have fulfilled at least some early promise. Further advances are urgently needed.

PMID- 25384991
TI  - The effect of photocatalytic oxidation on molecular size distribution profiles of
      humic acid.
AB  - The influence of photocatalytic degradation on molecular size fractionation (0.45
      MUm filtered, 100 kDa, 30 kDa and 3 kDa) of humic acid as a model compound of
      natural organic matter was investigated. The results were evaluated using UV-vis
      parameters, dissolved organic carbon (DOC) and excitation emission matrix (EEM)
      fluorescence spectral features. EEM fluorescence signatures displayed an
      irradiation period dependent transformation of humic-like fluorophores to fulvic
      like fluorophores in accordance with the photocatalytic mineralization of HA.
      Molecular size distribution profiles expressed the formation of lower molecular
      size (<3 kDa) fractions through oxidative degradation of humic acid of higher
      molecular size fractions (100 kDa and 30 kDa fractions). The fluorescence-derived
      index (fluorescence intensity (FI), represented by the ratio of the emission
      intensity at lambdaemis = 450 nm to that at lambdaemis = 500 nm, following the
      excitation at lambdaexc = 370 nm) was also investigated. The use of EEM features
      has proven to be a useful tool for monitoring the effect of photocatalytic
      degradation on the structure and molecular size distribution profile of HA. 

PMID- 25384992
TI  - Radiographic, clinical, and patients' assessment of segmental direct vertebral
      body derotation versus simple rod derotation in main thoracic adolescent
      idiopathic scoliosis: a prospective, comparative cohort study.
AB  - PURPOSE: The application of vertebral body derotation (DVBD) is still
      controversial by now; the purpose of this prospective cohort study was to compare
      comprehensive outcomes between segmental DVBD and simple rod derotation (SRD)
      especially in main thoracic adolescent idiopathic scoliosis. METHODS: 36 patients
      in DVBD group and 45 patients in SRD group were with a 2-year follow-up. Among
      them, 19 DVBD patients and 16 SRD patients received CT scan examinations.
      RESULTS: There were no significant difference between the groups in preoperative
      main thoracic Cobb, apical vertebral rotation and rib hump. Apical vertebral
      rotation measured from CT scans was 9.7 degrees  +/- 2.0 degrees  versus 15.3
      degrees  +/- 2.4 degrees  (p < 0.001) postoperatively in the DVBD and SRD
      patients, respectively. At 2-year follow-up, the main thoracic Cobb was 14.2
      degrees  +/- 1.6 degrees  versus 14.7 degrees  +/- 1.7 degrees  (p = 0.18), rib
      hump was 6.4 degrees  +/- 3.8 degrees  versus 6.8 degrees  +/- 3.1 degrees  (p =
      0.60) in DVBD group and SRD group. Patients' assessments of both groups were
      improved in Spinal Appearance Questionnaire (SAQ) and Scoliosis Research Society
      22 Questionnaire (SRS-22), but showed no significant difference at follow-up (p =
      0.47 and 0.60). CONCLUSION: Although segmental DVBD showed excellent radiographic
      correction of axial spinal deformity postoperatively, there was no more
      correction of clinical rib hump or better patients' assessment than SRD at follow
      up in our data.

PMID- 25384993
TI  - Dual growing rod treatment in early onset scoliosis: the effect of repeated
      lengthening surgeries on thoracic growth and dimensions.
AB  - PURPOSE: To investigate changes in thoracic dimensions (TDs) following repeated
      lengthening surgeries after dual growing rod treatment of early onset scoliosis
      and thereby its effect on thoracic growth. METHODS: All EOS patients treated with
      dual growing rod technique in Peking Union Medical College Hospital from June
      2004 to June 2014 were retrospectively reviewed. Thoracic spine height (T1-T12),
      total spine height (T1-S1), maximal coronal chest width and pelvic inlet width
      (PIW) were measured on the posteroanterior X-ray images after initial growing rod
      insertion surgery and after each lengthening surgery. Absolute TDs measurements
      were normalized by PIW. Changes of absolute and normalized TDs measurements with
      age and number of lengthening surgeries were analyzed. RESULTS: Radiographs of
      229 surgeries of 53 EOS patients were measured, including 49 images after initial
      growing rod insertion surgery and 180 images of lengthening surgeries.
      Significant positive correlations between age and all three absolute TDs were
      found (P < 0.01) whereas significant negative correlations between age and all
      three normalized TDs (P < 0.01) were identified. Similarly, negative correlations
      were also identified between number of lengthening surgeries and the three
      normalized TDs (P < 0.01). Significant differences of normalized TDs were
      identified between initial surgery and the first lengthening through covariance
      analysis (P < 0.01). Yet, such differences were seldom seen between every two
      adjacent lengthening surgeries. CONCLUSIONS: Growing rod technique could maintain
      TDs growth through repeated lengthening procedures but the growth rate was
      compromised as the number of lengthening procedures increased.

PMID- 25384994
TI  - Use of a pathway quality improvement care bundle to reduce mortality after
      emergency laparotomy.
AB  - BACKGROUND: Emergency laparotomies in the U.K., U.S.A. and Denmark are known to
      have a high risk of death, with accompanying evidence of suboptimal care. The
      emergency laparotomy pathway quality improvement care (ELPQuiC) bundle is an
      evidence-based care bundle for patients undergoing emergency laparotomy,
      consisting of: initial assessment with early warning scores, early antibiotics,
      interval between decision and operation less than 6 h, goal-directed fluid
      therapy and postoperative intensive care. METHODS: The ELPQuiC bundle was
      implemented in four hospitals, using locally identified strategies to assess the
      impact on risk-adjusted mortality. Comparison of case mix-adjusted 30-day
      mortality rates before and after care-bundle implementation was made using risk
      adjusted cumulative sum (CUSUM) plots and a logistic regression model. RESULTS:
      Risk-adjusted CUSUM plots showed an increase in the numbers of lives saved per
      100 patients treated in all hospitals, from 6.47 in the baseline interval (299
      patients included) to 12.44 after implementation (427 patients included) (P <
      0.001). The overall case mix-adjusted risk of death decreased from 15.6 to 9.6
      per cent (risk ratio 0.614, 95 per cent c.i. 0.451 to 0.836; P = 0.002). There
      was an increase in the uptake of the ELPQuiC processes but no significant
      difference in the patient case-mix profile as determined by the mean Portsmouth
      Physiological and Operative Severity Score for the enUmeration of Mortality and
      morbidity risk (0.197 and 0.223 before and after implementation respectively; P =
      0.395). CONCLUSION: Use of the ELPQuiC bundle was associated with a significant
      reduction in the risk of death following emergency laparotomy.

PMID- 25384996
TI  - Carbon-ion scanning lung treatment planning with respiratory-gated phase
      controlled rescanning: simulation study using 4-dimensional CT data.
AB  - BACKGROUND: To moving lung tumors, we applied a respiratory-gated strategy to
      carbon-ion pencil beam scanning with multiple phase-controlled rescanning (PCR).
      In this simulation study, we quantitatively evaluated dose distributions based on
      4-dimensional CT (4DCT) treatment planning. METHODS: Volumetric 4DCTs were
      acquired for 14 patients with lung tumors. Gross tumor volume, clinical target
      volume (CTV) and organs at risk (OARs) were delineated. Field-specific target
      volumes (FTVs) were calculated, and 48Gy(RBE) in a single fraction was prescribed
      to the FTVs delivered from four beam angles. The dose assessment metrics were
      quantified by changing the number of PCR and the results for the ungated and
      gated scenarios were then compared. RESULTS: For the ungated strategy, the mean
      dose delivered to 95% of the volume of the CTV (CTV-D95) was in average 45.3 +/-
      0.9 Gy(RBE) even with a single rescanning (1 * PCR). Using 4 * PCR or more
      achieved adequate target coverage (CTV-D95 = 46.6 +/- 0.3 Gy(RBE) for ungated 4 *
      PCR) and excellent dose homogeneity (homogeneity index =1.0 +/- 0.2% for ungated
      4 * PCR). Applying respiratory gating, percentage of lung receiving at least 20
      Gy(RBE) (lung-V20) and heart maximal dose, averaged over all patients,
      significantly decreased by 12% (p < 0.05) and 13% (p < 0.05), respectively.
      CONCLUSIONS: Four or more PCR during PBS-CIRT improved dose conformation to
      moving lung tumors without gating. The use of a respiratory-gated strategy in
      combination with PCR reduced excessive doses to OARs.

PMID- 25384997
TI  - White matter abnormalities in major depressive disorder with melancholic and
      atypical features: A diffusion tensor imaging study.
AB  - AIM: The DSM-IV recognizes some subtypes of major depressive disorder (MDD). It
      is known that the effectiveness of antidepressants differs among the MDD
      subtypes, and thus the differentiation of the subtypes is important. However,
      little is known as to structural brain changes in MDD with atypical features
      (aMDD) in comparison with MDD with melancholic features (mMDD), which prompted us
      to examine possible differences in white matter integrity assessed with diffusion
      tensor imaging (DTI) between these two subtypes. METHODS: Subjects were 21
      patients with mMDD, 24 with aMDD, and 37 age- and sex-matched healthy volunteers
      whose DTI data were obtained by 1.5 tesla magnetic resonance imaging. We compared
      fractional anisotropy and mean diffusivity value derived from DTI data on a voxel
      by-voxel basis among the two diagnostic groups and healthy subjects. RESULTS:
      There were significant decreases of fractional anisotropy and increases of mean
      diffusivity in patients with MDD compared with healthy subjects in the corpus
      callosum, inferior fronto-occipital fasciculus, and left superior longitudinal
      fasciculus. However, we detected no significant difference in any brain region
      between mMDD and aMDD. CONCLUSION: Our results suggest that patients with MDD had
      reduced white matter integrity in some regions; however, there was no major
      difference between aMDD and mMDD.

PMID- 25384998
TI  - Filling a critical practice gap: experience with a dermatology day treatment
      center at Mayo Clinic.
AB  - BACKGROUND: Intensive treatment options are lacking for patients with severe skin
      disease recalcitrant to outpatient therapy. The availability of inpatient
      dermatology care has almost disappeared in many parts of the United States. One
      possible solution for this is a day treatment center for patients with severe
      dermatologic disease recalcitrant to outpatient therapy. METHODS: Descriptive
      study based on retrospective medical record review of all patients attending the
      day hospital for treatment in 2010. We collected data on patient demographics,
      distribution of admission diagnosis, treatments used, and length of stay.
      RESULTS: A total of 211 patients had 235 admissions. Mean age was 57.7 years
      (range 3.8-92.1 years). The most common indications for admission were dermatitis
      (139 admissions [59.2%]), psoriasis (58 [24.7%]), and mycosis fungoides (eight
      [3.4%]). The main treatment interventions were wet dressings (195 admissions
      [83.0%]) and Goeckerman treatment (38 [16.2%]). The median number of days of
      treatment was three (interquartile range, 2-5 days) for wet dressings and 22 days
      (interquartile range, 21-24 days) for Goeckerman therapy. CONCLUSIONS: The
      dermatology day treatment center provided intensive skin-directed therapy and
      filled a critical practice gap in the management of our patients with severe
      widespread skin diseases recalcitrant to outpatient therapy. We propose that the
      dermatology day treatment center is a valuable model that could be considered by
      both private practitioners and academic centers in the United States as an
      important adjunct to fill the gap in availability of intensive topical treatments
      for patients with severe skin disease.

PMID- 25384999
TI  - Overlooked and underserved: Widowed fathers with dependent-age children.
AB  - OBJECTIVE: Widowed fathers and their children are at heightened risk for poor
      coping and maladaptive psychosocial outcomes. This exploratory study is the first
      to explicitly examine the psychological characteristics of this population of
      fathers. METHOD: Some 259 fathers (mean age = 46.81; 90% Caucasian) with
      dependent-age children and whose wives had died from cancer within the previous
      five years completed a web-based survey that consisted of demographic questions,
      the Center for Epidemiologic Studies Depression Scale (CES-D), the Texas
      Inventory of Grief-Revised (TRIG-R), the Psychological Adaptation Scale (PAS),
      the Kansas Parental Satisfaction Scale (KPSS), and items assessing perceived
      parental efficacy. RESULTS: Fathers were found to have elevated depressive (CES-D
      mean = 22.6) and grief (TRIG-R mean = 70.3) symptomatology, low adaptation (PAS
      mean = 3.2), and high levels of stress related to their parenting role. They
      reported being satisfied with their parenting (KPSS mean = 15.8) and having met
      their own parental expectations. Multivariate analyses revealed an association
      between father's age and depression (p = <0.01), with younger fathers reporting
      greater depressive symptoms. Psychological adaptation was positively correlated
      with being in a romantic relationship (p = 0.02) and age of oldest child (p =
      0.02). SIGNIFICANCE OF RESULTS: The results of our exploratory study suggest
      that, while widowed fathers perceive themselves as meeting their parental
      responsibilities, it comes at a substantial psychological cost, with particularly
      high stress related to being a sole parent. These findings may help guide
      interventions for this neglected population and underscore the importance of
      developing targeted therapies and research protocols to address their needs.

PMID- 25385000
TI  - Isolation and classification of a novel marine Bacteroidetes as Frondibacter
      aureus gen. nov., sp. nov.
AB  - A facultatively anaerobic, Gram-stain negative, golden-yellow pigmented, non
      motile and rod-shaped bacterium, designated strain A5Q-67(T) was isolated from
      leaf litter collected at the mangrove estuary of Nakama River, Japan.
      Phylogenetic analysis based on the 16S rRNA gene sequence revealed the novel
      isolate was affiliated with the family Flavobacteriaceae of the phylum
      Bacteroidetes and that it showed highest sequence similarity (94.2 %) to
      Imtechella halotolerans K1(T). The strain could be differentiated phenotypically
      from recognized members of the family Flavobacteriaceae. The major fatty acids of
      strain A5Q-67(T) were identified as iso-C17:0 3-OH, summed feature 1 (iso-C15:1 H
      and/or C13:0 3-OH) and iso-C15:0 as defined by the MIDI system. The DNA G+C
      content was determined to be 36.7 mol%, the major respiratory quinone was
      identified as menaquinone 6 (MK-6) and a polar lipid profile was present
      consisting of phosphatidylethanolamine, two unidentified aminolipids and an
      unidentified lipid. From the distinct phylogenetic position and combination of
      genotypic and phenotypic characteristics, the strain is considered to represent a
      novel genus for which the name Frondibacter aureus gen. nov., sp. nov. is
      proposed. The type strain of F. aureus is A5Q-67(T) (=KCTC 32991(T) = NBRC
      110021(T)).

PMID- 25385002
TI  - A case of symmetrical drug-related intertriginous and flexural exanthema induced
      by acetaminophen.

PMID- 25385001
TI  - Preferential, enhanced breast cancer cell migration on biomimetic electrospun
      nanofiber 'cell highways'.
AB  - BACKGROUND: Aggressive metastatic breast cancer cells seemingly evade surgical
      resection and current therapies, leading to colonization in distant organs and
      tissues and poor patient prognosis. Therefore, high-throughput in vitro tools
      allowing rapid, accurate, and novel anti-metastatic drug screening are grossly
      overdue. Conversely, aligned nanofiber constitutes a prominent component of the
      late-stage breast tumor margin extracellular matrix. This parallel suggests that
      the use of a synthetic ECM in the form of a nanoscale model could provide a
      convenient means of testing the migration potentials of cancer cells to achieve a
      long-term goal of providing clinicians an in vitro platform technology to test
      the efficacy of novel experimental anti-metastatic compounds. METHODS:
      Electrospinning produces highly aligned, cell-adhesive nanofiber matrices by
      applying a strong electric field to a polymer-containing solution. The resulting
      fibrous microstructure and morphology closely resembles in vivo tumor
      microenvironments suggesting their use in analysis of migratory potentials of
      metastatic cancer cells. Additionally, a novel interface with a gel-based
      delivery system creates CXCL12 chemotactic gradients to enhance CXCR4-expressing
      cell migration. RESULTS: Cellular dispersions of MCF-10A normal mammary
      epithelial cells or human breast cancer cells (MCF-7 and MDA-MB-231) seeded on
      randomly-oriented nanofiber exhibited no significant differences in total or net
      distance traveled as a result of the underlying topography. Cells traveled ~2-5
      fold greater distances on aligned fiber. Highly-sensitive MDA-MB-231 cells
      displayed an 82% increase in net distance traversed in the presence of a CXCL12
      gradient. In contrast, MCF-7 cells exhibited only 31% increase and MCF-10A cells
      showed no statistical difference versus control or vehicle conditions. MCF-10A
      cells displayed little sensitivity to CXCL12 gradients, while MCF-7 cells
      displayed early sensitivity when CXCL12 concentrations were higher. MDA-MB-231
      cells displayed low relative expression levels of CXCR4, but high sensitivity
      resulting in 55-fold increase at late time points due to CXCL12 gradient
      dissipation. CONCLUSIONS: This model could create clinical impact as an in vitro
      diagnostic tool for rapid assessment of tumor needle biopsies to confirm
      metastatic tumors, their invasiveness, and allow high-throughput drug screening
      providing rapid development of personalized therapies.

PMID- 25385003
TI  - High incidence of stem loosening in association with periprosthetic femur
      fractures in previously well-fixed cementless grit-blasted tapered-wedge stems.
AB  - PURPOSE: Periprosthetic femur fracture is a potentially worrisome phenomenon for
      cementless stem fixation. The aim of this study was to document the incidence of
      stem loosening following periprosthetic femur fracture in previously well-fixed
      cementless grit-blasted tapered-wedge stems. METHODS: We identified 36
      periprosthetic femur fractures of either Vancouver B1 or B2 following hip
      arthroplasties using cementless grit-blasted tapered-wedge titanium stems at
      three participating institutions (GB group). The control group consisted of 21
      periprosthetic femur fractures of either Vancouver B1 or B2 following hip
      arthroplasties using cementless proximal porous-coated stems at the same
      institutions during the same period of study (PC group). All femoral stems had
      been in a well-fixed state before occurrence of fracture. All patients were
      treated surgically and femoral stem stability was assessed using preoperative
      radiographs and confirmed by intraoperative scrutinization. RESULTS: Seven
      (19.4%) of 36 fractures were Vancouver B1 and 29 (80.6%) were Vancouver B2 in the
      GB group, whereas 18 (85.7%) of 21 fractures were Vancouver B1 and 3 (14.3%) were
      Vancouver B2 in the PC group (P < 0.0001). The odds ratio for stem loosening was
      24.86 (95% CI, 5.69-108.63) in the GB group versus the PC group. CONCLUSIONS: Hip
      arthroplasty using cementless grit-blasted tapered-wedge titanium stems showed
      higher incidence of stem loosening in association with periprosthetic femur
      fracture than hip arthroplasty conducted using proximal porous-coated stems. A
      high index of suspicion of stem loosening might be necessary in periprosthetic
      femur fracture following hip arthroplasty using this type of stems.

PMID- 25385005
TI  - Transgenic mouse milk expressing human bile salt-stimulated lipase improves the
      survival and growth status of premature mice.
AB  - The lactating human mammary gland and the pancreas both produce bile salt
      stimulated lipase (BSSL), a lipolytic enzyme acting on a wide range of
      substrates, including triglyceride, cholesterol esters, and fat-soluble vitamins
      esters. Breast milk BSSL has a particularly important role in the digestion of
      milk fat by newborn infants. We report the generation of transgenic mice that
      harbored a human BSSL gene controlled by a mammary gland-specific promoter. BSSL
      levels in transgenic mouse milk were raised to 376.8 MUg/ml, corresponding to an
      activity of 9.15 U/ml. Premature wild-type neonates nursed by transgenic dams
      exhibited significantly higher survival rate than did the control neonates nursed
      by wild dams (95 vs. 83.3 % and, P < 0.05). They also showed 43.8 % greater body
      weight gain and 33.3 % lesser fecal crude fat levels than did the controls. This
      study provides significant evidence that increased levels of BSSL in milk may
      reduce mortality and improve the growth and fat absorption in premature mice
      during neonatal development.

PMID- 25385004
TI  - Application of chitosan-based nanocarriers in tumor-targeted drug delivery.
AB  - Cancer is one of the major malignant diseases in the world. Current anti tumor
      agents are restricted during the chemotherapy due to their poor solubility in
      aqueous media, multidrug resistance problems, cytotoxicity, and serious side
      effects to healthy tissues. Development of targeted drug nanocarriers would
      enhance the undesirable effects of anticancer drugs and also selectively deliver
      them to cancerous tissues. Variety of nanocarriers such as micelles, polymeric
      nanoparticles, liposomes nanogels, dendrimers, and carbon nanotubes have been
      used for targeted delivery of anticancer agents. These nanocarriers transfer
      loaded drugs to desired sites through passive or active efficacy mechanisms.
      Chitosan and its derivatives, due to their unique properties such as
      hydrophilicity, biocompatibility, and biodegradability, have attracted attention
      to be used in nanocarriers. Grafting cancer-specific ligands onto the Chitosan
      nanoparticles, which leads to ligand-receptor interactions, has been successfully
      developed as active targeting. Chitosan-conjugated components also respond to
      external or internal physical and chemical stimulus in targeted tumors that is
      called environment triggers. In this study, mechanisms of targeted tumor
      deliveries via nanocarriers were explained; specifically, chitosan-based
      nanocarriers in tumor-targeting drug delivery were also discussed. 

PMID- 25385006
TI  - Diminished testing benefits in young adults with attention-deficit hyperactivity
      disorder.
AB  - Memory retrieval has been shown to enhance the long-term retention of tested
      material; however, recent research suggests that limiting attention during
      retrieval can decrease the benefits of testing memory. The present study examined
      whether testing benefits are reduced in young adults with attention-deficit
      hyperactivity disorder (ADHD). College students with and without ADHD read three
      short prose passages, each followed by a free recall test, a restudy period or a
      distractor task. Two days later participants recalled the passages. Although
      participants without ADHD did not show a significant benefit of testing over
      restudying, testing did produce recall benefits relative to not taking a test.
      These testing benefits were diminished in participants with ADHD, who did not
      show any advantage of testing over either restudying or no test. The absence of
      testing benefits in the ADHD group is likely due in part to decreased recall on
      the initial test. These findings have implications for improving educational
      practices among individuals with ADHD and also speak to the need to examine
      individual differences in the effectiveness of testing as a learning strategy. 

PMID- 25385007
TI  - Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double
      trigger), in patients with low proportion of mature oocytes.
AB  - OBJECTIVE: Human chorionic gonadotropin (hCG) is usually used at the end of
      controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce
      final oocyte maturation and resumption of meiosis. Recently, the co
      administration of GnRH agonist and hCG for final oocyte maturation - 40 and 34 h
      prior to OPU, respectively (double trigger) was suggested to improve IVF outcome
      in patient with genuine empty follicle syndrome. In the present study, we aim to
      evaluate whether the double trigger might improve the proportions of metaphase-II
      (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number
      oocytes retrieved. PATIENTS AND METHODS: We compared the stimulation
      characteristics of 12 IVF cycles, which include the cycle with the double trigger
      to the same patients' previous IVF attempt, triggered with hCG-only. RESULTS:
      Patients who received the double trigger (study group) had a significantly higher
      number of mature oocytes - MII (6.5 versus 3.6 p < 0.008), number of embryos
      transferred (2.4 versus 1.1 p < 0.03), a significantly higher proportions of MII
      oocytes per number of oocytes retrieved (69.7% versus 47.1% p < 0.03) and a
      higher number of top quality embryos (3.1 versus 1 p < 0.02), as compared to
      their previous control cycles (hCG-only trigger). Six pregnancies were recorded
      in the study group and none in the control group. CONCLUSIONS: Co-administration
      of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU,
      respectively (double trigger) improves IVF outcome in patients with high
      proportion of immature oocytes.

PMID- 25385009
TI  - A mild dihydrobenzooxaphosphole oxazoline/iridium catalytic system for asymmetric
      hydrogenation of unfunctionalized dialins.
AB  - Air-stable P-chiral dihydrobenzooxaphosphole oxazoline ligands were designed and
      synthesized. When they were used in the iridium-catalyzed asymmetric
      hydrogenation of unfunctionalized 1-aryl-3,4-dihydronaphthalenes under one
      atmosphere pressure of H2 , up to 99:1 e.r. was obtained. High
      enantioselectivities were also observed in the reduction of the exocyclic imine
      derivatives of 1-tetralones. 

PMID- 25385010
TI  - Estimating Lifetime Costs of Social Care: A Bayesian Approach Using Linked
      Administrative Datasets from Three Geographical Areas.
AB  - We estimated lifetime costs of publicly funded social care, covering services
      such as residential and nursing care homes, domiciliary care and meals. Like
      previous studies, we constructed microsimulation models. However, our transition
      probabilities were estimated from longitudinal, linked administrative health and
      social care datasets, rather than from survey data. Administrative data were
      obtained from three geographical areas of England, and we estimated transition
      probabilities in each of these sites flexibly using Bayesian methods. This
      allowed us to quantify regional variation as well as the impact of structural and
      parameter uncertainty regarding the transition probabilities. Expected lifetime
      costs at age 65 were L20,200-27,000 for men and L38,700-49,000 for women,
      depending on which of the three areas was used to calibrate the model. Thus,
      patterns of social care spending differed markedly between areas, with mean costs
      varying by almost L10,000 (25%) across the lifetime for people of the same age
      and gender. Allowing for structural and parameter uncertainty had little impact
      on expected lifetime costs, but slightly increased the risk of very high costs,
      which will have implications for insurance products for social care through
      increasing requirements for capital reserves.

PMID- 25385008
TI  - Signatures of tumour immunity distinguish Asian and non-Asian gastric
      adenocarcinomas.
AB  - OBJECTIVE: Differences in gastric cancer (GC) clinical outcomes between patients
      in Asian and non-Asian countries has been historically attributed to variability
      in clinical management. However, recent international Phase III trials suggest
      that even with standardised treatments, GC outcomes differ by geography. Here, we
      investigated gene expression differences between Asian and non-Asian GCs, and if
      these molecular differences might influence clinical outcome. DESIGN: We compared
      gene expression profiles of 1016 GCs from six Asian and three non-Asian GC
      cohorts, using a two-stage meta-analysis design and a novel biostatistical method
      (RUV-4) to adjust for technical variation between cohorts. We further validated
      our findings by computerised immunohistochemical analysis on two independent
      tissue microarray (TMA) cohorts from Asian and non-Asian localities (n=665).
      RESULTS: Gene signatures differentially expressed between Asians and non-Asian
      GCs were related to immune function and inflammation. Non-Asian GCs were
      significantly enriched in signatures related to T-cell biology, including CTLA-4
      signalling. Similarly, in the TMA cohorts, non-Asian GCs showed significantly
      higher expression of T-cell markers (CD3, CD45R0, CD8) and lower expression of
      the immunosuppressive T-regulatory cell marker FOXP3 compared to Asian GCs
      (p<0.05). Inflammatory cell markers CD66b and CD68 also exhibited significant
      cohort differences (p<0.05). Exploratory analyses revealed a significant
      relationship between tumour immunity factors, geographic locality-specific
      prognosis, and postchemotherapy outcomes. CONCLUSIONS: Analyses of >1600 GCs
      suggest that Asian and non-Asian GCs exhibit distinct tumour immunity signatures
      related to T-cell function. These differences may influence geographical
      differences in clinical outcome, and the design of future trials particularly in
      immuno-oncology.

PMID- 25385011
TI  - High-throughput screening of formulations to optimize the thermal stability of a
      therapeutic monoclonal antibody.
AB  - Monoclonal antibodies (mAbs) are an important class of biotherapeutics.
      Successful development of a mAb depends not only on its biological activity but
      also on its physicochemical properties, such as homogeneity and stability. mAb
      stability is affected by its formulation. Among the many techniques used to study
      the stability of mAbs, differential scanning fluorimetry (DSF) offers both
      excellent throughput and minimal material consumption. DSF measures the
      temperature of the protein unfolding transition (Tm) based on the change in
      fluorescence intensity of the environmentally sensitive dye SYPRO Orange. With
      DSF adapted to a 96-well plate format, we have shown that low-pH or high-salt
      concentrations decrease the thermal stability of mAb1, whereas some excipients,
      such as sucrose, polysorbate 80, and sodium phosphate, increase its stability.
      The basal fluorescence of SYPRO Orange was enhanced by the presence of
      detergents, limiting the use of this approach to diluted detergent solutions.
      Throughput of DSF can be increased further with the use of a 384-well plate. DSF
      thermograms are in good agreement with the melting profiles obtained by
      differential scanning calorimetry (DSC). The Tms determined by DSF and DSC were
      well correlated, with the former being on average lower by 3  degrees C. 

PMID- 25385012
TI  - Logistics in the cell: cargoes and transportation.
AB  - Eukaryotic cells are large and thus require a vesicular transport system. The
      system involves the formation of membrane transport containers, their short- and
      long-distance movements, recognition of destination points, and fusion with other
      membranes. Understanding the molecular mechanisms of these processes is of
      theoretical and practical significance. This special issue of Biochemistry
      (Moscow) collects surveys and experimental articles describing various aspects of
      vesicular transport. 

PMID- 25385013
TI  - The role of motor proteins in signal propagation.
AB  - The signaling and transport systems of eucaryotic cells are tightly
      interconnected: intracellular transport along microtubules and microfilaments is
      required to position signaling-pathway components, while signaling molecules
      control activity of motor proteins and their interaction with tracks and cargoes.
      Recent data, however, give evidence that active transport is engaged in signaling
      as a means of signal transduction. This review focuses on this specific aspect of
      the interaction of two systems. 

PMID- 25385014
TI  - Characterization of Rabaptin-5 gamma isoform.
AB  - Rab GTPases are key regulators of intracellular membrane traffic acting through
      their effector molecules. Rabaptin-5 is a Rab5 effector in early endosome fusion
      and connects Rab5- and Rab4-positive membrane compartments owing to its ability
      to interact with Rab4 GTPase. Recent studies showed that Rabaptin-5 transcript is
      subjected to extensive alternative splicing, thus resulting in expression of
      Rabaptin-5 isoforms mostly bearing short deletions in the polypeptide chain. As
      interactions of a Rab GTPase with different effectors lead to different
      responses, functional characterization of Rabaptin-5 isoforms becomes an
      attractive issue. Indeed, it was shown that Rab GTPase effector properties of
      Rabaptin-5 and its alpha and delta isoforms are different. This work focused on
      another Rabaptin-5 isoform, Rabaptin-5gamma. Despite its ability to interact with
      Rab5, endogenously produced Rabaptin-5gamma was absent from early endosomes.
      Rather, it was found to be tightly associated with trans-Golgi network and
      partially localized to a Rab4-positive membrane compartment. The revealed
      intracellular localization of Rabaptin-5gamma indicates that it is not involved
      in Rab5-driven events; rather, it functions in other membrane transport steps.
      Our study signifies the role of alternative splicing in determination of
      functional activities of Rab effector molecules. 

PMID- 25385015
TI  - Receptor-mediated endocytosis and cytoskeleton.
AB  - Receptor-mediated endocytosis is the most specific pathway for macromolecules and
      macromolecular complexes generally designated as ligands to enter cells. Upon
      binding to their transmembrane receptors, the ligands enter endocytic vesicles
      that fuse with each other giving rise to the so-called early endosomes. The
      sorting of ligand-receptor complexes internalized in these endosomes depends on
      their nature: metabolic receptors are recycled back to the plasma membrane, while
      signaling receptors and their ligands (e.g. receptor tyrosine kinases or
      receptors associated with tyrosine kinase) are delivered to internal vesicles of
      the multivesicular late endosomes and finally are degraded after interaction with
      lysosomes. During these processes, endosomes undergo translocation from the cell
      periphery to the juxtanuclear region, which is accompanied by multiple fusion,
      invagination, tabulation, and membrane fission events. This review considers
      modern concepts of the sorting mechanisms of ligand-receptor complexes, the
      crosstalk between endosomes, microtubules, and actin, and the role of this
      crosstalk in endosome maturation. 

PMID- 25385016
TI  - Interaction of early secretory pathway and Golgi membranes with microtubules and
      microtubule motors.
AB  - This review summarizes the data describing the role of cellular microtubules in
      transportation of membrane vesicles - transport containers for secreted proteins
      or lipids. Most events of early vesicular transport in animal cells (from the
      endoplasmic reticulum to the Golgi apparatus and in the opposite recycling
      direction) are mediated by microtubules and microtubule motor proteins. Data on
      the role of dynein and kinesin in early vesicle transport remain controversial,
      probably because of the differentiated role of these proteins in the movements of
      vesicles or membrane tubules with various cargos and at different stages of
      secretion and retrograde transport. Microtubules and dynein motor protein are
      essential for maintaining a compact structure of the Golgi apparatus; moreover,
      there is a set of proteins that are essential for Golgi compactness. Dispersion
      of ribbon-like Golgi often occurs under physiological conditions in interphase
      cells. Golgi is localized in the leading part of crawling cultured fibroblasts,
      which also depends on microtubules and dynein. The Golgi apparatus creates its
      own system of microtubules by attracting gamma-tubulin and some microtubule
      associated proteins to membranes. Molecular mechanisms of binding microtubule
      associated and motor proteins to membranes are very diverse, suggesting the
      possibility of regulation of Golgi interaction with microtubules during cell
      differentiation. To illustrate some statements, we present our own data showing
      that the cluster of vesicles induced by expression of constitutively active
      GTPase Sar1a[H79G] in cells is dispersed throughout the cell after microtubule
      disruption. Movement of vesicles in cells containing the intermediate compartment
      protein ERGIC53/LMANI was inhibited by inhibiting dynein. Inhibiting protein
      kinase LOSK/SLK prevented orientation of Golgi to the leading part of crawling
      cells, but the activity of dynein was not inhibited according to data on the
      movement of ERGIC53/LMANI-marked vesicles. 

PMID- 25385017
TI  - Specific organization of Golgi apparatus in plant cells.
AB  - Microtubules, actin filaments, and Golgi apparatus are connected both directly
      and indirectly, but it is manifested differently depending on the cell
      organization and specialization, and these connections are considered in many
      original studies and reviews. In this review we would like to discuss what
      underlies differences in the structural organization of the Golgi apparatus in
      animal and plant cells: specific features of the microtubule cytoskeleton
      organization, the use of different cytoskeleton components for Golgi apparatus
      movement and maintenance of its integrity, or specific features of synthetic and
      secretory processes. We suppose that a dispersed state of the Golgi apparatus in
      higher plant cells cannot be explained only by specific features of the
      microtubule system organization and by the absence of centrosome as an active
      center of their organization because the Golgi apparatus is organized similarly
      in the cells of other organisms that possess the centrosome and centrosomal
      microtubules. One of the key factors determining the Golgi apparatus state in
      plant cells is the functional uniformity or functional specialization of stacks.
      The functional specialization does not suggest the joining of the stacks to form
      a ribbon; therefore, the disperse state of the Golgi apparatus needs to be
      supported, but it also can exist "by default". We believe that the dispersed
      state of the Golgi apparatus in plants is supported, on one hand, by dynamic
      connections of the Golgi apparatus stacks with the actin filament system and, on
      the other hand, with the endoplasmic reticulum exit sites distributed throughout
      the endoplasmic reticulum. 

PMID- 25385018
TI  - Dynamic phase microscopy reveals periodic oscillations of endoplasmic reticulum
      during network formation.
AB  - Dynamic phase microscopy was used to study the dynamic events of formation of the
      endoplasmic reticulum (ER) in interphase-arrested Xenopus egg extract. We have
      shown that the ER periodically oscillated in an ATP-dependent manner in the
      frequency range of 1.6-2.2 Hz, while the tubular membrane network formed in
      vitro. The spectral density, i.e. the pattern of a given frequency component in
      the Fourier spectrum, was strongly correlated with the dynamic events during
      microtubule-dependent and microtubule-independent ER network formation observed
      by video-enhanced contrast differential interference contrast and fluorescence
      microscopy. Because the 1.6-2.2 Hz frequency of oscillation during the network
      formation was detected both in the presence and absence of microtubules, it
      appears to be an intrinsic ATP-dependent ER membrane property. Several
      characteristic active and inactive stages of ER network formation were observed
      both in the presence and absence of microtubules. However, data analysis of these
      stages indicated that microtubules and dynein motor activity have a strong
      influence and a cooperative effect on the kinetics of ER formation by controlled
      fusion reaction.

PMID- 25385019
TI  - Intracellular transport based on actin polymerization.
AB  - In addition to the intracellular transport of particles (cargo) along
      microtubules, there are in the cell two actin-based transport systems. In the
      actomyosin system the transport is driven by myosin, which moves the cargo along
      actin microfilaments. This transport requires the hydrolysis of ATP in the myosin
      molecule motor domain that induces conformational changes in the molecule
      resulting in the myosin movement along the actin filament. The other actin-based
      transport system of the cell does not involve myosin or other motor proteins.
      This system is based on a unidirectional actin polymerization, which depends on
      ATP hydrolysis in actin polymers and is initiated by proteins bound to the
      surface of transported particles. Obligatory components of the actin-based
      transport are proteins of the WASP/Scar family and a complex of Arp2/3 proteins.
      Moreover, the actin-based systems often contain dynamin and cortactin. It is
      known that a system of actin filaments formed on the surface of particles, the so
      called "comet-like tail", is responsible for intracellular movements of
      pathogenic bacteria, micropinocytotic vesicles, clathrin-coated vesicles, and
      phagosomes. This movement is reproduced in a cell-free system containing extract
      of Xenopus oocytes. The formation of a comet-like structure capable of
      transporting vesicles from the plasma membrane into the cell depth has been
      studied in detail by high performance electron microscopy combined with electron
      tomography. A similar mechanism provides the movement of vesicles containing
      membrane rafts enriched with sphingolipids and cholesterol, changes in position
      of the nuclear spindle at meiosis, and other processes. This review will consider
      current ideas about actin polymerization and its regulation by actin-binding
      proteins and show how these mechanisms are realized in the intracellular actin
      based vesicular transport system. 

PMID- 25385020
TI  - Use of intracellular transport processes for targeted drug delivery into a
      specified cellular compartment.
AB  - Targeted drug delivery into the cell compartment that is the most vulnerable to
      effects of the corresponding drug is a challenging problem, and its successful
      solution can significantly increase the efficiency and reduce side effects of the
      delivered therapeutic agents. To accomplish this one can utilize natural
      mechanisms of cellular specific uptake of macromolecules by receptor-mediated
      endocytosis and intracellular transport between cellular compartments. A
      transporting construction combining the components responsible for different
      steps of intracellular transport is promising for creating multifunctional
      modular constructions capable of delivering the necessary therapeutic agent into
      a given compartment of type-specified cells. This review focuses on intracellular
      transport peculiarities along with approaches for designing such transporting
      constructions for new, more effective, and safer strategies for treatment of
      various diseases. 

PMID- 25385021
TI  - Plasticity of tumor cell migration: acquisition of new properties or return to
      the past?
AB  - During tumor development cancer cells pass through several stages when cell
      morphology and migration abilities change remarkably. These stages are named
      epithelial-mesenchymal and mesenchymal-amoeboid transitions. The molecular
      mechanisms underlying cell motility are changing during these transitions. As
      result of transitions the cells acquire new characteristics and modes of
      motility. Cell migration becomes more independent from the environmental
      conditions, and thus cell dissemination becomes more aggressive, which leads to
      formation of distant metastases. In this review we discuss the characteristics of
      each of the transitions, cell morphology, and the specificity of cellular
      structures responsible for different modes of cell motility as well as molecular
      mechanisms regulating each transition. 

PMID- 25385022
TI  - Role of microtubule cytoskeleton in regulation of endothelial barrier function.
AB  - Cytoplasmic microtubules are an obligatory component of the cytoskeleton of all
      types of cells. Microtubules are involved in many cellular processes including
      directed transport of vesicles and signaling molecules and changes in cell shape
      during its spreading, polarization, and movement. The intracellular organization
      of the system of microtubules and their dynamic properties are different in
      different types of cells because they play a key role in the implementation of a
      variety of cell and tissue functions, including the regulation of the endothelial
      barrier function. This review presents an overview of current studies on the
      properties of endothelial microtubules, their interaction with other components
      of the cytoskeleton and cell adhesion structures, and the role of microtubules in
      the regulation of the endothelial barrier function. 

PMID- 25385023
TI  - The c-di-GMP phosphodiesterase BifA is involved in the virulence of bacteria from
      the Pseudomonas syringae complex.
AB  - In a recent screen for novel virulence factors involved in the interaction
      between Pseudomonas savastanoi pv. savastanoi and the olive tree, a mutant was
      selected that contained a transposon insertion in a putative cyclic diguanylate
      (c-di-GMP) phosphodiesterase-encoding gene. This gene displayed high similarity
      to bifA of Pseudomonas aeruginosa and Pseudomonas putida. Here, we examined the
      role of BifA in free-living and virulence-related phenotypes of two bacterial
      plant pathogens in the Pseudomonas syringae complex, the tumour-inducing pathogen
      of woody hosts, P. savastanoi pv. savastanoi NCPPB 3335, and the pathogen of
      tomato and Arabidopsis, P. syringae pv. tomato DC3000. We showed that deletion of
      the bifA gene resulted in decreased swimming motility of both bacteria and
      inhibited swarming motility of DC3000. In contrast, overexpression of BifA in P.
      savastanoi pv. savastanoi had a positive impact on swimming motility and
      negatively affected biofilm formation. Deletion of bifA in NCPPB 3335 and DC3000
      resulted in reduced fitness and virulence of the microbes in olive (NCPPB 3335)
      and tomato (DC3000) plants. In addition, real-time monitoring of olive plants
      infected with green fluorescent protein (GFP)-tagged P. savastanoi cells
      displayed an altered spatial distribution of mutant DeltabifA cells inside olive
      knots compared with the wild-type strain. All free-living phenotypes that were
      altered in both DeltabifA mutants, as well as the virulence of the NCPPB 3335
      DeltabifA mutant in olive plants, were fully rescued by complementation with P.
      aeruginosa BifA, whose phosphodiesterase activity has been demonstrated. Thus,
      these results suggest that P. syringae and P. savastanoi BifA are also active
      phosphodiesterases. This first demonstration of the involvement of a putative
      phosphodiesterase in the virulence of the P. syringae complex provides
      confirmation of the role of c-di-GMP signalling in the virulence of this group of
      plant pathogens.

PMID- 25385025
TI  - Targeted use of endoscopic CO2 laser cricopharyngeal myotomy for improving
      swallowing function following head and neck cancer treatment.
AB  - BACKGROUND: Cricopharyngeal dysfunction following head and neck cancer treatment
      may lead to a significant reduction in oral intake. Carbon dioxide laser is an
      established procedure for the treatment of non-malignant cricopharyngeal
      disorders. We report our experience of laser cricopharyngeal myotomy with
      objective swallowing outcome measures, before and after treatment. METHODS: We
      identified 11 patients who had undergone carbon dioxide laser cricopharyngeal
      myotomy for dysphagia following radiotherapy, with or without chemotheraphy
      between January 2006 and July 2011. We analysed the swallowing outcomes following
      carbon dioxide laser cricopharyngeal myotomy by retrospective grading of pre- and
      post-procedure videofluoroscopic swallowing study of liquids, using the validated
      Modified Barium Swallow Impairment Profile. RESULTS: The median Modified Barium
      Swallow Impairment Profile score was 13 pre-myotomy and 10 post-myotomy. This
      difference between scores was non-significant (p = 0.41). The median,
      cricopharyngeal-specific Modified Barium Swallow Impairment Profile variables (14
      and 17) improved from 3 to 2, but were similarly non-significant (p = 0.16). We
      observed the improved Modified Barium Swallow Impairment Profile scores post
      procedure in the majority of patients. CONCLUSION: Endoscopic carbon dioxide
      laser cricopharyngeal myotomy remains a viable option in treatment-related
      cricopharyngeal dysfunction; its targeted role requires further prospective
      study. Objective analysis of the technique can be reported using the validated
      Modified Barium Swallow Impairment Profile.

PMID- 25385024
TI  - Neurophysiological evidence for remediation of reward processing deficits in
      chronic pain and opioid misuse following treatment with Mindfulness-Oriented
      Recovery Enhancement: exploratory ERP findings from a pilot RCT.
AB  - Dysregulated processing of natural rewards may be a central pathogenic process in
      the etiology and maintenance of prescription opioid misuse and addiction among
      chronic pain patients. This study examined whether a Mindfulness-Oriented
      Recovery Enhancement (MORE) intervention could augment natural reward processing
      through training in savoring as indicated by event-related brain potentials
      (ERPs). Participants were chronic pain patients at risk for opioid misuse who
      were randomized to 8 weeks of MORE (n = 11) or a support group control condition
      (n = 18). ERPs to images representing naturally rewarding stimuli (e.g.,
      beautiful landscapes, intimate couples) and neutral images were measured before
      and after 8 weeks of treatment. Analyses focused on the late positive potential
      (LPP)--an ERP response in the 400-1,000 ms time window thought to index
      allocation of attention to emotional information. Treatment with MORE was
      associated with significant increases in LPP response to natural reward stimuli
      relative to neutral stimuli which were correlated with enhanced positive
      affective cue-responses and reductions in opioid craving from pre- to post
      treatment. Findings suggest that cognitive training regimens centered on
      strengthening attention to natural rewards may remediate reward processing
      deficits underpinning addictive behavior.

PMID- 25385026
TI  - Retaining the nursing workforce: factors contributing to the reduction of nurses'
      turnover intention in Japan.
AB  - AIM: The aim of this study was to investigate the effects of psychological
      contract fulfilment, perceived advancement opportunities and age on reducing the
      turnover intention of nurses in Japan. BACKGROUND: The factors that contribute to
      and mitigate the intentions of nurses to leave their organisations need to be
      investigated to understand the determinants of nurse turnover better. However,
      there is a paucity of studies identifying these mitigating factors. METHODS:
      Potential participants were 1337 registered nurses and midwives, of whom 766
      participated in the study (a return rate of 57%). The data were analysed using a
      moderated regression analysis. RESULTS: Fulfilment of the psychological contract
      and perceived advancement opportunities independently and jointly contributed to
      a reduction in nurses' turnover intentions. The results also showed that nurses'
      ages were negatively correlated with their turnover intentions. CONCLUSIONS:
      Fulfilment of the psychological contract and advancement opportunities are
      important for reducing nurses' turnover intentions, especially among younger
      nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Clear guidelines/evaluations of
      contributions made by nurses and their organisations are needed to enhance the
      experience of nurses in terms of psychological contract fulfilment. Moreover, a
      structured advancement support system needs to be implemented to reduce nurses'
      turnover intentions.

PMID- 25385027
TI  - Spatial distribution of flood risk and quality of spatial management: case study
      in Odra Valley, Poland.
AB  - This article presents methodological solutions aimed at presenting the spatial
      distribution of flood risk and quality of spatial management (land use),
      indicating both those areas used reasonably and those requiring modification. The
      purpose was to identify key risk areas and risk-free areas from the point of view
      of human security and activity on the floodplains, based on the examples of the
      vicinities of Wroclaw and Raciborz in the Odra Valley, Poland. Due to recent
      climate change, Poland has suffered the effects of severe flooding (e.g., 1997,
      2001, 2010). The analyses conducted were motivated by the European Parliament and
      Council's recently implemented Directive 2007/60/WE, as well as by the demand for
      studies for local spatial planning. The analysis indicates that reasonably
      developed areas do not account for the majority of those studied, making up 36%
      of the Wroclaw area and 15% of the Raciborz area. 

PMID- 25385029
TI  - Has number of previous episodes any effect on response to group psychoeducation
      in bipolar patients? A 5-year follow-up post hoc analysis.
AB  - Colom F, Reinares M, Pacchiarotti I, Popovic D, Mazzarini L, Martinez-Aran A,
      Torrent C, Rosa A, Palomino-Otiniano R, Franco C, Bonnin CM, Vieta E. Has number
      of previous episodes any effect on response to group psychoeducation in bipolar
      patients? A 5-year follow-up post hoc analysis. OBJECTIVE: One of the main
      utilities of staging in bipolar disorder is enhancing the formulation of
      pharmacological and non-pharmacological treatment strategies. Hence, it is
      essential to ascertain whether the number of previous episodes influences
      treatment response. Hereby, we present a 5-year post hoc study on the efficacy of
      group psychoeducation for bipolar disorders according to the number of previous
      episodes. METHODS: For this subanalysis, we have compared the 5-year outcome of
      120 euthymic psychoeducated versus non-psychoeducated bipolar patients according
      to the number of previous episodes at study entry. RESULTS: Patients with more
      than seven episodes at study entry did not show any significant improvement with
      psychoeducation according to time to recurrence. Patients with more than 14
      episodes did not benefit from psychoeducation in terms of a reduction of time
      spent ill. Patients with 7 or 8 episodes showed a benefit in terms of fewer days
      spent in hypomania, depression, mixed episodes or any episodes but not mania,
      while patients with 9-14 episodes showed a benefit in terms of fewer days spent
      in hypomania and depression but not in mixed states or mania. Only patients who
      presented up to 6 episodes showed reduction in time spent in any episode
      polarity. CONCLUSION: The number of previous episodes clearly worsens response to
      psychoeducation, perhaps in a more subtle way than that observed with other
      psychological therapies. Psychoeducation should be delivered as soon as possible
      in the illness course, supporting the idea of early intervention.

PMID- 25385028
TI  - LASP1 is a HIF1alpha target gene critical for metastasis of pancreatic cancer.
AB  - LASP1 is an actin-binding protein associated with actin assembly dynamics in
      cancer cells. Here, we report that LASP1 is overexpressed in pancreatic ductal
      adenocarcinoma (PDAC) where it promotes invasion and metastasis. We found that
      LASP1 overexpression in PDAC cells was mediated by HIF1alpha through direct
      binding to a hypoxia response element in the LASP1 promoter. HIF1alpha stimulated
      LASP1 expression in PDAC cells in vitro and mouse tumor xenografts in vivo.
      Clinically, LASP1 overexpression in PDAC patient specimens was associated
      significantly with lymph node metastasis and overall survival. Overall, our
      results defined LASP1 as a direct target gene for HIF1alpha upregulation that is
      critical for metastatic progression of PDAC.

PMID- 25385030
TI  - Emotional vulnerability and cognitive control in patients with bipolar disorder
      and their healthy siblings: a pilot study.
AB  - Scheuch K, Braunig P, Gauggel S, Kliesow K, Sarkar R, Kruger S. Emotional
      vulnerability and cognitive control in patients with bipolar disorder and their
      healthy siblings: a pilot study. OBJECTIVE: There is evidence that, even in
      remission, patients with bipolar disorder (BD) have deficits in cognitive
      function and emotional regulation. Siblings of patients with BD are also reported
      to exhibit minor dysfunction in neuropsychological domains. In this study, we
      examined the interference of acute mood state with reaction time (RT) and
      response inhibition in euthymic patients with BD, in their healthy siblings and
      in healthy controls. METHODS: A total of 34 patients with bipolar I disorder, 22
      healthy siblings and 33 healthy controls performed a stop-signal paradigm after
      induction of a transient intense sadness and a relaxed mood state. The
      differences in RT and the response inhibition were compared between the groups.
      RESULTS: Euthymic patients with BD displayed a higher emotional reactivity
      compared with their siblings and with controls. Compared with controls, patients
      with BD showed longer RTs in a relaxed mood state and a delay in response
      inhibition during emotional activation. CONCLUSIONS: The present study provides
      evidence for the clinical observation that patients with BD have shorter RTs when
      in a state of emotional arousal rather than in a relaxed state. Inhibitory
      deficits in these patients may be because of a too strong emotional arousal. The
      results show that in patients with BD, relaxation and emotional arousal are
      inversely associated with performance in a neuropsychological task. This is in
      contrast to findings in healthy individuals suggesting a dysbalance in emotional
      regulation in these patients.

PMID- 25385031
TI  - Obesity is associated with previous suicide attempts in bipolar disorder.
AB  - Gomes FA, Kauer-Sant'Anna M, Magalhaes PV, Jacka FN, Dodd S, Gama CS, Cunha A,
      Berk M, Kapczinski F. Obesity is associated with previous suicide attempts in
      bipolar disorder. OBJECTIVE: There is a paucity of data about risk factors for
      suicide attempts in bipolar disorder. The aim of this study is to examine the
      association between suicide attempts and obesity in people with bipolar disorder.
      METHODS: Two hundred fifty-five DSM-IV out-patients with bipolar disorder were
      consecutively recruited from the Bipolar Disorder Program at Hospital das
      Clinicas de Porto Alegre and the University Hospital at the Universidade Federal
      de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with
      Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured
      protocol. History of suicide attempts was obtained from multiple information
      sources including patients, relatives and review of medical records. Patients
      with body mass index (BMI) >= 30 were classified as obese. RESULTS: Over 30% of
      the sample was obese and over 50% had a history of suicide attempt. In the
      multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06
      3.69, p = 0.03) as likely to have a history of suicide attempt(s). CONCLUSION:
      Our results emphasise the relevance of obesity as an associated factor of suicide
      attempts in bipolar disorder. Obesity may be seen as correlate of severity and as
      such, must be considered in the comprehensive management of bipolar patients.

PMID- 25385032
TI  - A Pilot, 15-month, randomised effectiveness trial of Risperidone long-acting
      injection (RLAI) versus oral atypical antipsychotic agents (AAP) in persons with
      bipolar disorder.
AB  - Chengappa KNR, Turkin SR, Schlicht PJ, Murphy SL, Brar JS, Fagiolini A, Houck PR,
      Garbutt RG, Fredrick N. A Pilot, 15-month, randomised effectiveness trial of
      Risperidone long acting injection (RLAI) versus oral atypical antipsychotic
      agents (AAP) in persons with bipolar disorder. OBJECTIVE: Long-acting injectible
      antipsychotic agents are rarely considered in the treatment of bipolar patients
      [bipolar disorder (BPD)]. We posited that BPD patients receiving risperidone long
      acting injections [Risperidone long-acting injections (RLAIs)] would experience
      fewer negative clinical events than those receiving oral atypical antipsychotic
      agents (AAP). METHODS: Adult BPD patients in a hypomanic, manic or mixed episode
      were randomised to either oral risperdone followed by RLAI (n = 23) or an AAP (n
      = 25) for 15 months. Any mood stabilizers were continued. An independent
      clinician board declared any clinical events that occurred but the treatment
      assignment was concealed. RESULTS: Nine of the 48 patients who participated in
      this study did not improve, leaving 39 patients in 1-year extension. RLAI
      patients received the following bi-weekly dosages: 25 mg (n = 9), 37.5 mg (n =
      8), and 50 mg (n = 6). The AAP group included aripiprazole (n = 11, 15-30
      mg/day), quetiapine (n = 8, 300-700 mg/day), olanzapine (n = 5, 15-25 mg/day),
      and ziprasidone, (n = 1, 160 mg/day). In total, 47 clinical events were declared.
      The RLAI-treated group experienced significantly fewer clinical events (mean:
      0.86 +/- 0.73) compared with the AAP group (1.61 +/- 1.29), t = 2.29, d.f. = 37,
      p = 0.028 (95% CI = 0.087-1.421). Of all, 50% of the AAP subjects gained >= 7% of
      their baseline body weight as did 38% of the RLAI-treated patients. CONCLUSIONS:
      RLAI-treated patients experienced significantly fewer negative clinical events.
      Further exploration should focus on which subtypes of BPD patients might benefit
      from RLAI treatment. Weight gain in BPD subjects requires clinical attention.
      Limitations include an open design, small sample size and the inability to
      conclude on whether this strategy is useful for depressive episodes.

PMID- 25385033
TI  - Bipolar disorder and comorbid obsessive-compulsive disorder is associated with
      higher rates of anxiety and impulse control disorders.
AB  - Issler CK, Monkul ES, Amaral JAMS, Tamada RS, Shavitt RG, Miguel EC, Lafer B.
      Bipolar disorder and comorbid obsessive-compulsive disorder is associated with
      higher rates of anxiety and impulse control disorders. OBJECTIVE: Although
      bipolar disorder (BD) with comorbid obsessive-compulsive disorder (OCD) is highly
      prevalent, few controlled studies have assessed this comorbidity. The objective
      of this study was to investigate the clinical characteristics and expression of
      comorbid disorders in female BD patients with OCD. METHOD: We assessed clinically
      stable female outpatients with BD: 15 with comorbid OCD (BD+OCD group) and 15
      without (BD/no-OCD group). All were submitted to the Structured Clinical
      Interview for DSM-IV, with additional modules for the diagnosis of kleptomania,
      trichotillomania, pathological gambling, onychophagia and skin picking. RESULTS:
      The BD+OCD patients presented more chronic episodes, residual symptoms and
      previous depressive episodes than the BD/no-OCD patients. Of the BD+OCD patients,
      86% had a history of treatment-emergent mania, compared with only 40% of the
      BD/no-OCD patients. The following were more prevalent in the BD+OCD patients than
      the BD/no-OCD patients: any anxiety disorder other than OCD; impulse control
      disorders; eating disorders; and tic disorders. CONCLUSION: Female BD patients
      with OCD may represent a more severe form of disorder than those without OCD,
      having more depressive episodes and residual symptoms, and being at a higher risk
      for treatment-emergent mania, as well as presenting a greater anxiety and impulse
      control disorder burden.

PMID- 25385034
TI  - Wfs1-deficient animals have brain-region-specific changes of Na+, K+-ATPase
      activity and mRNA expression of alpha1 and beta1 subunits.
AB  - Mutations in the WFS1 gene, which encodes the endoplasmic reticulum (ER)
      glycoprotein, cause Wolfram syndrome, a disease characterized by juvenile-onset
      diabetes mellitus, optic atrophy, deafness, and different psychiatric
      abnormalities. Loss of neuronal cells and pancreatic beta-cells in Wolfram
      syndrome patients is probably related to the dysfunction of ER stress regulation,
      which leads to cell apoptosis. The present study shows that Wfs1-deficient mice
      have brain-region-specific changes in Na(+),K(+)-ATPase activity and in the
      expression of the alpha1 and beta1 subunits. We found a significant (1.6-fold)
      increase of Na-pump activity and beta1 subunit mRNA expression in mice lacking
      the Wfs1 gene in the temporal lobe compared with their wild-type littermates. By
      contrast, exposure of mice to the elevated plus maze (EPM) model of anxiety
      decreased Na-pump activity 1.3-fold in the midbrain and dorsal striatum and 2.0
      fold in the ventral striatum of homozygous animals compared with the nonexposed
      group. Na-pump alpha1 -subunit mRNA was significantly decreased in the dorsal
      striatum and midbrain of Wfs1-deficient homozygous animals compared with wild
      type littermates. In the temporal lobe, an increase in the activity of the Na
      pump is probably related to increased anxiety established in Wfs1-deficient mice,
      whereas the blunted dopamine function in the forebrain of Wfs1-deficient mice may
      be associated with a decrease of Na-pump activity in the dorsal and ventral
      striatum and in the midbrain after exposure to the EPM.

PMID- 25385036
TI  - Neuroendocrinology: Role for adiponectin in effects of exercise in depression.

PMID- 25385035
TI  - Paraganglioma and phaeochromocytoma: from genetics to personalized medicine.
AB  - Paragangliomas and phaeochromocytomas are neuroendocrine tumours whose
      pathogenesis and progression are very strongly influenced by genetics. A germline
      mutation in one of the susceptibility genes identified so far explains ~40% of
      all cases; the remaining 60% are thought to be sporadic cases. At least one-third
      of these sporadic tumours contain a somatic mutation in a predisposing gene.
      Genetic testing, which is indicated in every patient, is guided by the clinical
      presentation as well as by the secretory phenotype and the immunohistochemical
      characterization of the tumours. The diagnosis of an inherited form drives
      clinical management and tumour surveillance. Different 'omics' profiling methods
      have provided a neat classification of these tumours in accordance with their
      genetic background. Transcriptomic studies have identified two main molecular
      pathways that underlie development of these tumours, one in which the hypoxic
      pathway is activated (cluster 1) and another in which the MAPK and mTOR
      (mammalian target of rapamycin) signalling pathways are activated (cluster 2).
      DNA methylation profiling has uncovered a hypermethylator phenotype in tumours
      related to SDHx genes (a group of genes comprising SDHA, SDHB, SDHC, SDHD and
      SDHAF2) and revealed that succinate acts as an oncometabolite, inhibiting 2
      oxoglutarate-dependent dioxygenases, such as hypoxia-inducible factor prolyl
      hydroxylases and histone and DNA demethylases. 'Omics' data have suggested new
      therapeutic targets for patients with a malignant tumour. In the near future, new
      'omics'-based tests are likely to be transferred into clinical practice with the
      goal of establishing personalized medical management for affected patients. 

PMID- 25385037
TI  - Diabetes: beta cells at last.

PMID- 25385039
TI  - [Healthcare policy at the EU level: strategies for action of the European
      Commission exemplified by patient safety].
AB  - Patient safety is an important issue in European healthcare policy. Given the
      fact that healthcare falls within the competence of the EU Member States, this
      paper highlights the capabilities of the European Commission to promote patient
      safety. The potential added value for the topic that can arise at the EU level is
      critically discussed. 

PMID- 25385040
TI  - [Simulation-based training in anesthesia and emergency medicine: preparation for
      the unexpected: on the way to new standards of education in Germany].
AB  - Medical expertise consists of knowledge, professional skills and individual
      attitudes. Training and education of this expertise starts in medical school and
      develops throughout the qualification process of anesthesists and emergency
      physicians. Medical decisions are not only rational but also intuitive. The
      combination of these characteristics cannot and should not be trained on
      patients. The implementation of modern simulation techniques offers the
      opportunity to train for emergency situations similar to training systems in the
      energy industry and aviation. Repetitive training of rare emergency situations
      brings routine to seldomly used procedures. In simulation training mistakes can
      be detected and systematically corrected. The team interactions and soft skills
      can also be focussed on. Video analysis gives the participant the opportunity for
      self-reflection and can lead to correction of individual behavior patterns. This
      dimension of education cannot be done in real patient care. This training goes
      far beyond the level of skills training. Through simulation training involves the
      whole team, the communication and the interaction between the team members in
      medically challenging situations. Crisis resource management leads to measurable
      improvements in patient safety and safety culture as well as personnel
      satisfaction. 

PMID- 25385041
TI  - [Risk and error management: can medicine benefit from lessons learned in
      aviation?].
AB  - Flight safety could be increased by approximately one million times within the
      last 100 years by rigorously analyzing and correcting system deficiencies.
      Aviation safety strategies can help to increase patient safety. A few examples:
      the pilot in command takes critical safety decisions without economical
      restraints. Safety-relevant decisions should be made as if the captain's family
      would be on board. Organizational deficiencies can be detected using a non
      punitive reporting system. The pilot is encouraged to report errors without the
      fear of being punished. Well-trained specialists, supporting and correcting each
      other are an important prerequisite for error detection and error correction. An
      optimal hierarchical gradient helps to reduce risks. Strategies for risk
      reduction require more personnel, increase costs and slow down the working speed.
      Safety is expensive and safety can be bought. 

PMID- 25385042
TI  - Locally controlling mesenchymal stem cell morphogenesis by 3D PDGF-BB gradients
      towards the establishment of an in vitro perivascular niche.
AB  - The perivascular niche is a complex microenvironment containing mesenchymal stem
      cells (MSCs), among other perivascular cells, as well as temporally organized
      biochemical and biophysical gradients. Due to a lack of conclusive phenotypic
      markers, MSCs' identity, heterogeneity and function within their native niche
      remain poorly understood. The in vitro reconstruction of an artificial three
      dimensional (3D) perivascular niche would offer a powerful alternative to study
      MSC behavior under more defined conditions. To this end, we here present a
      poly(ethylene glycol)-based in vitro model that begins to mimic the
      spatiotemporally controlled presentation of biological cues within the in vivo
      perivascular niche, namely a stably localized platelet-derived growth factor B
      (PDGF-BB) gradient. We show that 3D-encapsulated MSCs respond to soluble PDGF-BB
      by proliferation, spreading, and migration in a dose-dependent manner. In
      contrast, the exposure of MSCs to 3D matrix-tethered PDGF-BB gradients resulted
      in locally restricted morphogenetic responses, much as would be expected in a
      native perivascular niche. Thus, the herein presented artificial perivascular
      niche model provides an important first step towards modeling the role of MSCs
      during tissue homeostasis and regeneration. 

PMID- 25385043
TI  - Evaluation of a Rapid Immunochromatographic Treponemal Antibody Test Comparing
      the Treponema Pallidum Particle Agglutination Assay.
AB  - BACKGROUND: In addition to conventional tests, several methods for detection of
      treponema-specific antibodies in clinical settings have been recently introduced.
      We aim to comparatively evaluate a rapid immunochromatographic test (ICT) for
      Treponema pallidum specific antibody (SD Bioline Syphilis 3.0) and the T.
      pallidum particle agglutination (TPPA) assay. METHODS: In all, 132 serum samples
      from 78 syphilis patients and 54 syphilis-negative controls were analyzed. SD
      Bioline Syphilis 3.0 test (Standard Diagnostic, Inc., Yongin, Korea) was
      evaluated and compared to Serodia TPPA assay (Fujirebio, Inc., Tokyo, Japan). All
      discrepant results between the two assays were repeatedly tested and evaluated by
      the fluorescent treponemal antibody-absorption (FTA-ABS) assay. Test
      reproducibility and 95% limit of detection of SD Bioline Syphilis 3.0 were
      determined across three different lots for seven consecutive days in triplicate.
      Interference due to autoantibodies and pregnancy was also tested. RESULTS:
      Percent agreement between SD Bioline Syphilis 3.0 and TPPA assays was 99.2%.
      Sensitivity and specificity were 100%, respectively. In TPPA assay, test-to-test,
      day-to-day, and lot-to-lot variations were not identified until 1:320 titer
      (eightfold dilutions). There was no interference due to the presence of
      antinuclear antibodies or samples or pregnancy. CONCLUSIONS: Percent agreement of
      SD Syphilis 3.0 and TPPA was very good. Sensitivity and specificity were
      appropriate for T. pallidum antibody detection. Thus, a rapid ICT could be
      suitable for syphilis antibody detection.

PMID- 25385044
TI  - Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis
      and cell invasion by targeting HIF-1alpha in vitro.
AB  - Overexpression of hypoxia-inducible factor-1 (HIF-1) alpha, a transcription
      factor which immortalizes tumors by inducing expression of the genes involved in
      cell survival, migration and angiogenesis, is closely associated with poor
      prognosis, increased risk of metastasis and increased mortality. Oligomer
      procyanidins (F2), a natural fraction from grape seeds, has been demonstrated to
      have antioxidant and antitumor activities, however the antitumor effect of F2
      targeting HIF-1alpha remains unknown. The present study showed that F2 markedly
      decreased HIF-1alpha and the expression of its target genes in cancer cells
      through inactivating the EGFR-PI3K-AKT-mTOR and MAPK-ERK1/2 pathways. Moreover,
      F2 suppressed vascular endothelial growth factor (VEGF) and matrix
      metalloproteinases (MMP)-2 expressions, followed by the inhibition of tumor
      angiogenesis and cell invasion in a HIF-1alpha-dependent manner. Collectively,
      these findings indicate that the antitumor effect of F2 is, at least in part,
      mediated by suppressing HIF-1alpha-dependent pathway, and suggest that F2 may be
      a potentially useful agent for treatment of human cancer. 

PMID- 25385045
TI  - Radiation-induced matrix metalloproteinases limit natural killer cell-mediated
      anticancer immunity in NCI-H23 lung cancer cells.
AB  - Radiotherapy has been used to treat cancer for >100 years and is required by
      numerous patients with cancer. Ionizing radiation effectively inhibits the growth
      of cancer cells by inducing cell death and increasing anticancer immunity,
      through the induction of natural killer group 2 member D ligands (NKG2DLs);
      however, adverse effects have also been reported, including the promotion of
      metastasis. Matrix metalloproteinases (MMPs) are induced by ionizing radiation
      and have an important role in the invasion and metastasis of cancer cells.
      Previously, MMPs were demonstrated to increase the shedding of NKG2DLs, which may
      reduce the surface expression of NKG2DLs on cancer cells. As a consequence, the
      cancer cells may escape natural killer (NK)-mediated anticancer immunity. In the
      present study, NCI-H23 human non-small cell lung cancer cells were used to
      investigate the combined effects of ionizing radiation and MMP inhibitors on the
      expression levels of NKG2DLs. Ionizing radiation increased the expression of MMP2
      and ADAM metalloproteinase domain 10 protease, as well as NKG2DLs. The combined
      treatment of ionizing radiation and MMP inhibitors increased the surface
      expression levels of NKG2DLs and resulted in the increased susceptibility of the
      cancer cells to NK-92 natural killer cells. Furthermore, soluble NKG2DLs were
      increased in the media by ionizing radiation and blocked by MMP inhibitors. The
      present study suggests that radiotherapy may result in the shedding of soluble
      NKG2DLs, through the induction of MMP2, and combined treatment with MMP
      inhibitors may minimize the adverse effects of radiotherapy.

PMID- 25385046
TI  - Rer1 and calnexin regulate endoplasmic reticulum retention of a peripheral myelin
      protein 22 mutant that causes type 1A Charcot-Marie-Tooth disease.
AB  - Peripheral myelin protein 22 (PMP22) resides in the plasma membrane and is
      required for myelin formation in the peripheral nervous system. Many PMP22
      mutants accumulate in excess in the endoplasmic reticulum (ER) and lead to the
      inherited neuropathies of Charcot-Marie-Tooth (CMT) disease. However, the
      mechanism through which PMP22 mutants accumulate in the ER is unknown. Here, we
      studied the quality control mechanisms for the PMP22 mutants L16P and G150D,
      which were originally identified in mice and patients with CMT. We found that the
      ER-localised ubiquitin ligase Hrd1/SYVN1 mediates ER-associated degradation
      (ERAD) of PMP22(L16P) and PMP22(G150D), and another ubiquitin ligase, gp78/AMFR,
      mediates ERAD of PMP22(G150D) as well. We also found that PMP22(L16P), but not
      PMP22(G150D), is partly released from the ER by loss of Rer1, which is a Golgi
      localised sorting receptor for ER retrieval. Rer1 interacts with the wild-type
      and mutant forms of PMP22. Interestingly, release of PMP22(L16P) from the ER was
      more prominent with simultaneous knockdown of Rer1 and the ER-localised chaperone
      calnexin than with the knockdown of each gene. These results suggest that CMT
      disease-related PMP22(L16P) is trapped in the ER by calnexin-dependent ER
      retention and Rer1-mediated early Golgi retrieval systems and partly degraded by
      the Hrd1-mediated ERAD system. 

PMID- 25385048
TI  - Management of pelvic discontinuity in revision total hip arthroplasty: a review
      of the literature.
AB  - Pelvic discontinuity is a complex problem in revision total hip arthroplasty.
      Although rare, the incidence is likely to increase due to the ageing population
      and the increasing number of total hip arthroplasties being performed. The
      various surgical options available to solve this problem include plating, massive
      allografts, reconstruction rings, custom triflanged components and tantalum
      implants. However, the optimal solution remains controversial. None of the known
      methods completely solves the major obstacles associated with this problem, such
      as restoration of massive bone loss, implant failure in the short- and long-term
      and high complication rates. This review discusses the diagnosis, decision
      making, and treatment options of pelvic discontinuity in revision total hip
      arthroplasty. 

PMID- 25385047
TI  - Work, family and social environment in patients with Fibromyalgia in Spain: an
      epidemiological study: EPIFFAC study.
AB  - BACKGROUND: Fibromyalgia (FM) is a condition characterized by widespread pain,
      estimated to affect 2.4% of the Spanish population. Nowadays, there are no
      consistent epidemiological studies on the actual impact of the disease on work
      and family of these patients in a representative manner; therefore, the purpose
      of the study is to analyze the impact on family, employment and social
      environment in a representative sample of patients with FM attending Primary
      Public Care Centers in Spain. METHODS: We carried out an epidemiological study,
      with a probability sampling procedure, stratified, relative to the municipality
      size and the number of health centres, seeking territorial representation. The
      survey was conducted using a self-administered structured questionnaire. RESULTS:
      A sample of 325 patients with FM was studied in 35 Primary Health Care Centers
      (PHCCs). The sample is composed of 96.6% of women, 51.9 (8) years of mean
      (standard deviation- sd) age. Ninety-three percent of the patients have worked
      throughout their life. Mean (sd) age onset of symptoms was 37 (11) years and
      diagnosis of FM was established 6.6 (8) years later. Family Environment: Fifty
      nine percent of patients have difficulties with their partner. Forty-four percent
      of the patients report to be fairly or totally dependent on a family member in
      household chores. The household income decreased a mean (sd) of 708 (504)
      Euros/month in 65% of the patients. In 81% of the patients, there was an increase
      in extra expenses related to the disease with a mean (sd) of 230 (192)
      Euros/month. Working environment: At the moment of the study, 45% of the patients
      had work activity (34% were working and 11% were at sick leave), 13% were
      unemployed seeking job and 42% were not in the labor force. Twenty-three percent
      of patients had some degree of permanent work disability pension. Social
      Environment: The degree of satisfaction with health care professionals was low
      and twenty-six percent of the patients were members of specific patients
      associations. CONCLUSIONS: This study finds that people with FM who visit PHCCs
      of Spain experience a high impact on families and employment with heavy loss of
      ability to work.

PMID- 25385049
TI  - Analysis of hip range of motion in everyday life: a pilot study.
AB  - Patients undergoing total hip arthroplasty are increasingly younger and have a
      higher demand concerning hip range of motion. To date, there is no clear
      consensus as to the amplitude of the "normal hip" in everyday life. It is also
      unknown if the physical examination is an accurate test for setting the values of
      true hip motion. The purpose of this study was: 1) to precisely determine the
      necessary hip joint mobility for everyday tasks in young active subjects to be
      used in computer simulations of prosthetic models in order to evaluate
      impingement and instability during their practice; 2) to assess the accuracy of
      passive hip range of motion measurements during clinical examination. A total of
      4 healthy volunteers underwent Magnetic Resonance Imaging and 2 motion capture
      experiments. During experiment 1, routine activities were recorded and applied to
      prosthetic hip 3D models including nine cup configurations. During experiment 2,
      a clinical examination was performed, while the motion of the subjects was
      simultaneously captured. Important hip flexion (mean range 95 degrees -107
      degrees ) was measured during daily activities that could expose the prosthetic
      hip to impingement and instability. The error made by the clinicians during
      physical examination varied in the range of +/-10 degrees , except for flexion
      and abduction where the error was higher. This study provides useful information
      for the surgical planning to help restore hip mobility and stability, when
      dealing with young active patients. The physical examination seems to be a
      precise method for determining passive hip motion, if care is taken to stabilise
      the pelvis during hip flexion and abduction. 

PMID- 25385050
TI  - Proceedings from the American College of Rheumatology Reproductive Health Summit:
      the management of fertility, pregnancy, and lactation in women with autoimmune
      and systemic inflammatory diseases.

PMID- 25385051
TI  - Prognostic factors for the course of functional status of patients with ALS: a
      systematic review.
AB  - The progressive course of amyotrophic lateral sclerosis (ALS) results in an ever
      changing spectrum of the care needs of patients with ALS. Knowledge of prognostic
      factors for the functional course of ALS may enhance clinical prediction and
      improve the timing of appropriate interventions. Our objective was to
      systematically review the evidence regarding prognostic factors for the rate of
      functional decline of patients with ALS, assessed with versions of the ALS
      Functional Rating Scale (ALSFRS). Two reviewers independently assessed the
      methodological quality of the thirteen included studies using the Quality in
      Prognosis Studies (QUIPS) tool. The overall quality of evidence for each
      prognostic factor was assessed using the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) approach, considering risk of bias,
      imprecision, inconsistency, indirectness, and publication bias. The quality of
      evidence for the prognostic value of age at onset, site of onset, time from
      symptom onset to diagnosis, and ALSFRS-Revised baseline score was low, mainly due
      to the limited data and inconsistency of results in the small number of studies
      included. The prognostic value of initial rate of disease progression, age at
      diagnosis, forced vital capacity, frontotemporal dementia, body mass index, and
      comorbidity remains unclear. We conclude that the current evidence on prognostic
      factors for functional decline in ALS is insufficient to allow the development of
      a prediction tool that can support clinical decisions. Given the limited data,
      future prognostic studies may need to focus on factors that have a predictive
      value for a decline in ALSFRS(-R) domain scores, preferably based on
      internationally collected and shared data. 

PMID- 25385052
TI  - Evaluation of CNS involvement in myotonic dystrophy type 1 and type 2 by
      transcranial sonography.
AB  - Myotonic dystrophies (DMs) are clinically similar but distinct multisystemic
      diseases related to different repeat expansion mutations. CNS involvement is one
      important aspect of both, myotonic dystrophy type 1 and type 2 (DM1, DM2).
      Transcran ial sonography (TCS) has become a reliable diagnostic tool in the
      evaluation of several CNS disorders. The aim of this study was to evaluate TCS
      findings in DM-patients in correlation with their clinical status. Thirty-one DM
      patients (DM1 = 17; DM2 = 14) were examined clinically and sonographically by
      independent physicians. Echogenicities of basal ganglia and mesencephalic regions
      were assessed according to the examination protocol for extrapyramidal disorders
      using a Toshiba Aplio((r)) XG ultrasound system. TCS abnormalities were
      correlated to clinical findings and secondly compared to 31 controls. Ventricle
      diameters were additionally compared to 3T-MRI volumetry. Nine patients (29 %)
      showed hyperechogenicity of substantia nigra. Mesencephalic raphe was
      hypoechogenic in nine (29 %) DM-patients and was more frequently in DM1 patients
      (p = 0.021). Width of third ventricle was significantly larger in the patient
      group (p = 0.021) and correlated with MRI-based volumetry (R (2) = 0.756).
      Pathological raphe signal was observed mainly in patients suffering from daytime
      sleepiness (sensitivity = 42.1 %, specificity = 88.9 %, p = 0,044), while
      alterations did not correlate with symptoms of depression. As a novel finding, a
      relation between mesencephalic raphe echogenicity and excessive daytime
      sleepiness could be identified in our DM-patients. An alteration of serotonergic
      raphe structures might be involved in the pathogenesis of hypersomnia in DM. TCS
      allows for measurement of third ventricle enlargement as a feasible bedside test.

PMID- 25385053
TI  - Theta burst stimulation over the supplementary motor area in Parkinson's disease.
AB  - To investigate whether a period of continuous theta burst stimulation (cTBS) over
      the supplementary motor area (SMA) induces cortical plasticity and thus improves
      bradykinesia in Parkinson's disease (PD) in the medication ON and OFF state. In
      total, 26 patients with Parkinson's disease were tested with both real and sham
      stimulation. The group was divided into an OFF-medication (4 females, mean age 65
      years, disease duration 6 years) and an ON-medication group (7 females, mean age
      61 years, disease duration 7 years) with each containing 13 individuals. Both
      groups were evaluated in terms of electrophysiological (motor-evoked potentials)
      and behavioural [Purdue Pegboard test (PPT), UPDRS motor subscore] parameters
      before (baseline condition) and after a 40-second period of real or sham
      continuous theta burst stimulation over the SMA ON and OFF dopaminergic drugs.
      Patients in the OFF group demonstrated an improved UPDRS III score (p < 0.05) and
      a better performance in the PPT for the less affected side (p < 0.025) compared
      to baseline after real stimulation. However, electrophysiological parameters did
      not change in either the ON or the OFF state. cTBS over the SMA has a mild effect
      on motor symptoms of the upper limb in the OFF state of PD patients. In contrast,
      stimulation did not change cortico-spinal excitability. A lack of change (i.e. no
      plasticity) to brain stimulation protocols is a known finding in PD. A clinical
      improvement in the OFF state, however, contrasts with this and the mechanism of
      these induced changes is worth further exploration.

PMID- 25385054
TI  - Reversed-phase liquid chromatography with electrospray mass detection and 1H and
      13C NMR characterization of new process-related impurities, including forced
      degradants of efavirenz: related substances correlated to the synthetic pathway.
AB  - In this study, a stability-indicating reversed-phase liquid chromatographic
      electrospray mass spectrometric method was developed and validated for the
      determination of process-related impurities and forced degradants of Efavirenz in
      bulk drugs. Efavirenz was subjected to acid, alkaline hydrolysis, H2O2 oxidation,
      photolysis, and thermal stress. Significant degradation was observed during
      alkaline hydrolysis, and the degradants were isolated on a mass-based
      purification system and characterized by high-resolution mass spectrometry,
      positive electrospray ionization tandem mass spectrometry, and (1)H and (13)C NMR
      spectroscopy. Accurate mass measurement and NMR spectroscopy revealed the
      possible structure of process-related impurities and degradant under stress
      conditions. The acceptable separation was accomplished on Waters bondapak C18
      column (250 mm * 4.6 mm; 5 MUm), using 5 mM ammonium acetate and acetonitrile as
      a mobile phase in a gradient elution mode at a flow rate of 1.0 mL/min. The
      eluents were monitored by diode array detector at 247 nm and quantitation limits
      were obtained in the range of 0.1-2.5 MUg/mL for Efavirenz, degradants, and
      process-related impurities. The liquid chromatography method was validated with
      respect to accuracy, precision, linearity, robustness, and limits of detection
      and quantification as per International Conference on Harmonization guidelines.

PMID- 25385055
TI  - Selumetinib for the treatment of cancer.
AB  - Introduction: The MAPK pathway is essential for regulation of cellular
      proliferation, differentiation and survival. Multiple human cancers have
      demonstrated activation of Raf-mitogen-activated kinase kinase (MEK)
      extracellular signal-related kinase signaling, a hallmark of these tumors.
      Efforts to inhibit various protein kinases in this pathway have led to the
      development of MEK inhibitors. Selumetinib is one such drug, functioning as an
      oral, selective non-ATP-competitive MEK1/2 inhibitor. Areas covered: In this
      article, the authors discuss the underlying biology of MEK inhibition and its
      rationale in cancer treatment. Furthermore, the authors summarize the clinical
      development of selumetinib in various tumor types, from initial Phase I studies
      to randomized Phase II studies, both as monotherapy or in combination with other
      chemotherapeutics. Expert opinion: Given the frequency of activated MAPK
      signaling in multiple tumor types, the potent MEK inhibitor selumetinib had
      strong preclinical and early clinical rationale, particularly in those tumors
      harboring KRAS or BRAF mutations. While efficacy signals have been seen in
      various tumor types treated with selumetinib, better biomarkers are needed to
      select patients most likely to respond favorably to this agent. Furthermore,
      combinatorial therapy with selumetinib and other targeted agents can likely be
      optimized to maximize the antitumor effect of inhibiting RAS/MAPK signaling.

PMID- 25385056
TI  - Combined cytotoxic effect of UV-irradiation and TiO2 microbeads in normal
      urothelial cells, low-grade and high-grade urothelial cancer cells.
AB  - The differentiation of urothelial cells results in normal terminally
      differentiated cells or by alternative pathways in low-grade or high-grade
      urothelial carcinomas. Treatments with traditional surgical and
      chemotherapeutical approaches are still inadequate and expensive, as bladder
      tumours are generally highly recurrent. In such situations, alternative
      approaches, using irradiation of the cells and nanoparticles, are promising. The
      ways in which urothelial cells, at different differentiation levels, respond to
      UV-irradiation (photolytic treatment) or to the combination of UV-irradiation and
      nanoparticles (photocatalytic treatment), are unknown. Here we tested
      cytotoxicity of UV-irradiation on (i) normal porcine urothelial cells (NPU), (ii)
      human low-grade urothelial cancer cells (RT4), and (iii) human high-grade
      urothelial cancer cells (T24). The results have shown that 1 minute of UV
      irradiation is enough to kill 90% of the cells in NPU and RT4 cultures, as
      determined by the live/dead viability assay. On the other hand, the majority of
      T24 cells survived 1 minute of UV-irradiation. Moreover, even a prolonged UV
      irradiation for 30 minutes killed <50% of T24 cells. When T24 cells were pre
      supplemented with mesoporous TiO2 microbeads and then UV-irradiated, the
      viability of these high-grade urothelial cancer cells was reduced to <10%, which
      points to the highly efficient cytotoxic effects of TiO2 photocatalysis. Using
      electron microscopy, we confirmed that the mesoporous TiO2 microbeads were
      internalized into T24 cells, and that the cell's ultrastructure was heavily
      compromised after UV-irradiation. In conclusion, our results show major
      differences in the sensitivity to UV-irradiation among the urothelial cells with
      respect to cell differentiation. To achieve an increased cytotoxicity of
      urothelial cancer cells, the photocatalytic approach is recommended. 

PMID- 25385057
TI  - Radiologic and laboratory differences in patients with tuberculous and
      parapneumonic pleural effusions showing non-lymphocytic predominance and high
      adenosine deaminase levels.
AB  - PURPOSE: Tuberculous pleural effusion (TPE) is characterized by lymphocytic
      predominance and high adenosine deaminase (ADA) levels. However, TPEs sometimes
      present non-lymphocytic predominance, and parapneumonic effusion (PPE) often
      exceeds the cutoff value of ADA for TPE. Thus, the differential diagnosis of
      cases with pleural fluid (PF) showing non-lymphocytic predominance and high ADA
      levels is challenging. However, limited data concerning the clinical differences
      in these patients are available. METHODS: A retrospective study was conducted on
      TPE and PPE patients with PF showing non-lymphocytic predominance and ADA levels
      >=40 U/L in 2009-2013 in a South Korean tertiary referral hospital. The clinical,
      laboratory, and computed tomography (CT) findings between the groups were
      analyzed using multivariate logistic regression to develop a prediction model
      with independent factors for TPE. RESULTS: Among 353 patients with TPE, 24 (6.8
      %) showed PF with non-lymphocytic predominance and ADA levels of >=40 U/L. Twenty
      eight PPE patients who presented PF findings comparable with those of TPE
      patients were included in the control group. In the final analysis, PF ADA levels
      >58 U/L and nodular lung lesions on CT were independent positive predictors,
      while loculated effusion was an independent negative predictor for TPE. Using the
      prediction model, a score >= +3 provided a sensitivity of 88 %, specificity of 93
      %, positive predictive value of 91 %, and negative predictive value of 90 % for
      TPE. CONCLUSION: PF ADA levels, nodular lung lesions, and loculated pleural
      effusion may help differentiate TPE from PPE in patients with PF showing non
      lymphocytic predominance and ADA levels >=40 U/L.

PMID- 25385058
TI  - Serum aryl hydrocarbon receptor ligand activity is associated with insulin
      resistance and resulting type 2 diabetes.
AB  - AIMS: Dioxin or dioxin-like compounds are ligands of the aryl hydrocarbon
      receptor (AhR), which is a ligand-activated nuclear transcription factor. There
      are limited studies about the association of serum AhR ligand activities and
      T2DM. Our objective was to investigate the association of serum AhR ligand
      activities with T2DM and its related metabolic parameters. METHODS: This case
      control study involved 83 subjects with T2DM as well as age-, sex-, and body mass
      index (BMI)-matched subjects with impaired glucose tolerance (IGT, n = 130) and
      normal glucose tolerance (NGT, n = 83). Serum AhR ligand activities were measured
      using a cell-based AhR ligand assay and standardized as 2,3,7,8
      tetrachlorodibenzo-p-dioxin equivalents (TCDDeq, pmol/l). RESULTS: The T2DM group
      had the highest AhR ligand activities compared to the IGT and NGT groups [median
      (interquartile range), 68.1 (53.1, 81.5), 60.2 (45.8, 75.1), and 53.3 (46.1,
      63.7) pmol/l, respectively; P = 0.003]. In the multivariate analysis, the log2
      transformed TCDDeq levels were significantly associated with the risk of T2DM
      after adjusting for age, sex, and BMI (odds ratio 2.26, 95 % confidence interval
      1.34-3.82; P = 0.002). In nondiabetic subjects, serum AhR ligand activities
      showed a positive correlation with fasting glucose and insulin concentrations and
      the homeostasis model assessment of insulin resistance, but showed a negative
      correlation with adiponectin concentrations. CONCLUSIONS: Serum AhR ligand
      activities were higher in the T2DM group and were correlated with the parameters
      of insulin resistance. Further investigation is required to elucidate the causal
      relationship between AhR ligand activity and T2DM.

PMID- 25385059
TI  - Knowledge of the harms of tobacco use among patients with bladder cancer.
AB  - BACKGROUND: The objective of this study was to determine tobacco use knowledge
      and attribution of cause in patients with newly diagnosed bladder cancer.
      METHODS: A stratified, random sample of bladder cancer survivors diagnosed
      between 2006 and 2009 was obtained from the California Cancer Registry.
      Respondents were surveyed about tobacco use, risk factors, and sources of
      information on the causes of bladder cancer. Contingency tables and logistic
      regression analyses were used to evaluate tobacco use knowledge and beliefs.
      RESULTS: Of 1198 eligible participants, 790 (66%) completed the survey. Sixty
      eight percent of the cohort had a history of tobacco use, and 19% were active
      smokers at diagnosis. Tobacco use was the most cited risk factor for bladder
      cancer, with active smokers more knowledgeable than former smokers or never
      smokers (90% vs 64% vs 61%, respectively; P<.001). Urologists were the
      predominant source of information and were cited most often by active smokers
      (82%). In multivariate analyses, active smokers had 6.37 times greater odds (95%
      confidence interval, 3.35-12.09) than never smokers of endorsing tobacco use as a
      risk factor for bladder cancer, and smokers who named the urologist as their
      information source had 2.80 times greater odds (95% confidence interval, 1.77
      4.43) of believing tobacco use caused their cancer. CONCLUSIONS: Patients'
      smoking status and primary source of information were associated with knowledge
      of the harms of tobacco use and, in smokers, acknowledgment that tobacco use
      increased the risk of their own disease. Urologists play a critical role in
      ensuring patients' knowledge of the connection between smoking and bladder
      cancer, particularly for active smokers who may be motivated to quit.

PMID- 25385061
TI  - Comparison of ketorolac 0.4% and nepafenac 0.1% for the prevention of cystoid
      macular oedema after phacoemulsification: prospective placebo-controlled
      randomised study.
AB  - PURPOSE: To compare the anti-inflammatory efficacy of ketorolac of tromethamine
      0.4% and nepafenac 0.1% eye drops for prophylaxis of cystoid macular oedema (CME)
      after small-incision cataract extraction. METHODS: Patients were assigned
      randomly to three groups. Group 1 patients received a topical artificial tear
      substitute (placebo); group 2 received ketorolac tromethamine 0.4% (Acular LS,
      Allergan) and group 3 received nepafenac 0.1% (Nevanac, Alcon). The incidence and
      severity of CME were evaluated by retinal foveal thickness on optical coherence
      tomography (OCT) after 1, 4 and 12 weeks. RESULTS: One hundred and twenty-six
      eyes of 126 patients were included in this study. The between-group differences
      in visual outcomes, central corneal thickness and endothelial cell density were
      not statistically significant. In all retinal thickness measurements, an increase
      was detected starting from the postoperative first week until 12 weeks. There was
      no statistically significant difference between the three groups in any
      measurement performed by spectral-domain OCT. CONCLUSIONS: Used prophylactically
      after uneventful cataract surgery, non-steroidal anti-inflammatory drugs were not
      efficacious in preventing macular oedema compared with placebo. TRIAL
      REGISTRATION NUMBER: ClinicalTrials: NCT02084576.

PMID- 25385062
TI  - Volumetric modulated arc therapy for lung stereotactic radiation therapy can
      achieve high local control rates.
AB  - PURPOSE: The aim of this study was to report the outcome of primary or metastatic
      lung cancer patients undergoing volumetric modulated arc therapy for stereotactic
      body radiation therapy (VMAT-SBRT). METHODS AND MATERIALS: From October 2010 to
      December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT
      using an Elekta-synergy system. All patients were treated with an abdominal
      compressor. The gross tumor volumes were contoured on 10 respiratory phases
      computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into
      internal target volumes (ITVs). The planning target volume (PTV) margin was
      isotropically taken as 5 mm. Treatment was performed with a D95 prescription of
      50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy
      in 7 fractions (12 cases) for central tumor. RESULTS: Among the 67 patients, the
      median age was 73 years (range, 59-95 years). Of the patients, male was 72% and
      female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%)
      and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40-1162
      days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary
      lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6
      patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The
      median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed
      radiation pneumonitis required by steroid administration. Actuarial local control
      rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3
      years in primary and metastatic lung cancer, respectively (p =0.59). Overall
      survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20%
      at 3 years in primary and metastatic lung cancer, respectively (p =0.12).
      CONCLUSIONS: Use of VMAT-based delivery of SBRT in primary in metastatic lung
      tumors demonstrates high local control rates and low risk of normal tissue
      complications.

PMID- 25385063
TI  - High psychiatric comorbidity in adolescents with dissociative disorders.
AB  - AIM: The aim of this study was to evaluate psychiatric comorbidity rates and
      patterns in a sample of clinically referred adolescents diagnosed with
      dissociative disorders (DD) by using a structured interview. METHODS: All
      participants completed a comprehensive test battery, which consisted of a
      questionnaire for sociodemographic data and clinical history, Child Posttraumatic
      Stress Reaction Index, Childhood Abuse and Neglect Questionnaire and the
      Adolescent Dissociative Experiences Scale. Diagnosis was made by the Structured
      Clinical Interview for DSM-IV Dissociative Disorders. Psychiatric comorbidity was
      assessed using the Schedule for Affective Disorders and Schizophrenia for School
      Age Children - Present and Lifetime Version. RESULTS: A total of 25 adolescent
      subjects aged 12-18 years participated in the study. Ten adolescents were
      diagnosed as having dissociative identity disorder and 15 of them were diagnosed
      as having dissociative disorder-not otherwise specified based on the Structured
      Clinical Interview for DSM-IV Dissociative Disorders findings. Adolescents with
      dissociative identity disorder were found to have higher scores on the Adolescent
      Dissociative Experiences Scale and Child Posttraumatic Stress Reaction Index than
      the dissociative disorder-not otherwise specified group. Sexual and physical
      abuses were also found to be among the main traumatic events. Incest was reported
      in six cases of the study sample. All subjects had at least one comorbid
      psychiatric disorder. The most common psychiatric diagnoses were major depressive
      disorder (n = 25; 100%) and post-traumatic stress disorder (n = 22; 88%).
      CONCLUSION: High psychiatric comorbidity rates were found in adolescents
      diagnosed with DD. A prevalent history of abuse and traumatic events was
      represented. Clinicians should be aware of the impacts of DD on adolescents'
      mental health.

PMID- 25385064
TI  - C3d adjuvant effects are mediated through the activation of C3d-specific
      autoreactive T cells.
AB  - Complement fragment C3d covalently attached to antigens enhances immune
      responses, particularly for antigens lacking T-cell epitopes. Enhancement has
      been attributed to receptor cross-linking between complement receptor CR2 (CD21)
      and polysaccharide antigen to surface IgM on naive B cells. Paradoxically, C3d
      has still been shown to increase immune responses in CD21 knockout mice,
      suggesting that an auxiliary activation pathway exists. In prior studies, we
      demonstrated the CD21-independent C3d adjuvant effect might be due to T-cell
      recognition of C3d T-helper epitopes processed and presented by major
      histocompatibility complex class II on the B-cell surface. C3d peptide sequences
      containing concentrated clusters of putative human C3 T-cell epitopes were
      identified using the epitope-mapping algorithm, EpiMatrix. These peptide
      sequences were synthesized and shown in vitro to bind multiple human leukocyte
      antigen (HLA)-DR alleles with high affinity, and induce interferon-gamma
      responses in healthy donor peripheral blood mononuclear cells. In the present
      studies, we establish further correlations between HLA binding and HLA-specific
      lymphocyte reactions with select epitope clusters. In addition, we show that the
      T-cell phenotype of C3d-specific reactive T cells is CD4(+)CD45RO(+) memory T
      cells. Finally, mutation of a single T-cell epitope residing within the P28
      peptide segment of C3d resulted in significantly diminished adjuvant activity in
      BALB/c mice. Collectively, these studies support the hypothesis that the
      paradoxical enhancement of immune responses by C3d in the absence of CD21 is due
      to internalization and processing of C3d into peptides that activate autoreactive
      CD4(+) T-helper cells in the context of HLA class II. 

PMID- 25385065
TI  - Roles of autophagy in HIV infection.
AB  - Autophagy is a major cellular pathway, which at basal levels regulates and
      maintains the cytoplasmic environment through the capture, isolation and
      digestion of intracellular materials in a specialized structure called an
      autophagosome. The unique ability of autophagy to degrade large targets, such as
      damaged and surplus organelles, intracellular microbes and protein aggregates,
      has made it a prime focus in inflammation and microbial research. Indeed,
      autophagy has been shown to be involved in a number of infectious and
      inflammatory pathologies, by which it may confer protection against intracellular
      microbes, be targeted by microbes for evasion or be hijacked for microbe
      biogenesis. In addition, autophagy helps regulate the intracellular and global
      immune response to both extracellular and intracellular pathogens. Here we review
      the current literature on the interactions between autophagy and HIV among
      different immune cells and discuss new research that re-emphasizes the role of
      inflammation in HIV-mediated CD4(+) T cell death. 

PMID- 25385066
TI  - Lymphocyte repertoire selection and intracellular self/non-self-discrimination:
      historical overview.
AB  - Immunological self/non-self-discrimination is conventionally seen as an
      extracellular event, involving interactions been receptors on T cells pre
      educated to discriminate and peptides bound to major histocompatibility complex
      proteins (pMHCs). Mechanisms by which non-self peptides might first be sorted
      intracellularly to distinguish them from the vast excess of self-peptides have
      long been called for. Recent demonstrations of endogenous peptide-specific
      clustering of pMHCs on membrane rafts are indicative of intracellular enrichment
      before surface display. The clustering could follow the specific aggregation of a
      foreign protein that exceeded its solubility limit in the crowded intracellular
      environment. Predominantly entropy-driven, this homoaggregation would colocalize
      identical peptides, thus facilitating their collective presentation.
      Concentrations of self-proteins are fine-tuned over evolutionary time to avoid
      this. Disparate observations, such as pyrexia and female susceptibility to
      autoimmune disease, can be explained in terms of the need to cosegregate cognate
      pMHC complexes internally before extracellular display. 

PMID- 25385068
TI  - Development of methane emission factors for enteric fermentation in cattle from
      Benin using IPCC Tier 2 methodology.
AB  - The objective of this study was to develop emission factors (EF) for methane
      (CH4) emissions from enteric fermentation in cattle native to Benin. Information
      on livestock characteristics and diet practices specific to the Benin cattle
      population were gathered from a variety of sources and used to estimate EF
      according to Tier 2 methodology of the 2006 Intergovernmental Panel on Climate
      Change (IPCC) Guidelines for National Greenhouse Gas Inventories. Most cattle
      from Benin are Bos taurus represented by Borgou, Somba and Lagune breeds. They
      are mainly multi-purpose, being used for production of meat, milk, hides and
      draft power and grazed in open pastures and crop lands comprising tropical
      forages and crops. Estimated enteric CH4 EFs varied among cattle breeds and
      subcategory owing to differences in proportions of gross energy intake expended
      to meet maintenance, production and activity. EFs ranged from 15.0 to 43.6, 16.9
      to 46.3 and 24.7 to 64.9 kg CH4/head per year for subcategories of Lagune, Somba
      and Borgou cattle, respectively. Average EFs for cattle breeds were 24.8, 29.5
      and 40.2 kg CH4/head per year for Lagune, Somba and Borgou cattle, respectively.
      The national EF for cattle from Benin was 39.5 kg CH4/head per year. This
      estimated EF was 27.4% higher than the default EF suggested by IPCC for African
      cattle with the exception of dairy cattle. The outcome of the study underscores
      the importance of obtaining country-specific EF to estimate global enteric CH4
      emissions.

PMID- 25385069
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis: a 20-year single-center
      experience.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are life-threatening diseases that are most frequently caused by drugs.
      OBJECTIVES: The purpose of this study was to summarize 20 years of experience
      with SJS and TEN in the largest dermatology clinic in Serbia. METHODS: The study
      included 38 patients treated during the period 1993-2012. The patients were
      classified into three groups according to whether they were diagnosed with SJS, a
      condition representing an overlap of SJS and TEN (SJS/TEN), or TEN. Patients with
      TEN were also divided into three groups according to the modality of therapy:
      supportive therapy (ST) only (n = 3); ST plus systemic corticosteroids (SC) (n =
      8); and ST plus SC plus IV immunoglobulins (IVIG) (n = 6). RESULTS: The study
      population included 13 SJS patients, eight SJS/TEN patients, and 17 TEN patients.
      The disease had started at a mean +/- standard deviation (SD) of 7.1 +/- 3.5 days
      after the commencement of treatment with the offending drug. The disease resulted
      in three lethal outcomes, all of which occurred in TEN patients. However, the
      predicted mortality for the whole group was 5.6 in 38 patients, whereas that for
      the TEN group was 3.97 in 17 patients. The differences between actual and
      predicted rates of mortality were not significant. Among the three groups of TEN
      patients, there were no significant differences in the commencement of re
      epithelialization or the duration of hospitalization. CONCLUSIONS: In the present
      study, nonsteroidal anti-inflammatory and anti-infective drugs were the most
      frequent causative agents (eight patients in each group). In the group of SJS and
      SJS/TEN patients treated with ST and SC, the mortality rate was 0%. In TEN
      patients, the mortality rate was 17.6% (three of 17 patients). There were no
      significant differences in mortality rate among the three TEN treatment groups,
      but the results may have been biased by the small number of patients.

PMID- 25385067
TI  - CD3bright signals on gammadelta T cells identify IL-17A-producing Vgamma6Vdelta1+
      T cells.
AB  - Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important
      role at mucosal sites in a wide range of immune responses including infection,
      allergy and auto-immunity. gammadelta T cells are recognized as IL-17 producers,
      but based on the level of CD3 expression, we now define the remarkable ability of
      a CD3(bright) gammadelta T-cell subset with an effector memory phenotype to
      rapidly produce IL-17A, but not interferon-gamma. CD3(bright) gammadelta T cells
      uniformly express the canonical germline encoded Vgamma6/Vdelta1(+) T-cell
      receptor. They are widely distributed with a preferential representation in the
      lungs and skin are negatively impacted in the absence of retinoic acid receptor
      related orphan receptor gammat expression or endogenous flora. This population
      responded rapidly to various stimuli in a mechanism involving IL-23 and NOD-like
      receptor family, pyrin domain containing 3 (NLRP3)-inflammasome-dependent IL
      1beta. Finally, we demonstrated that IL-17-producing CD3(bright) gammadelta T
      cells responded promptly and strongly to pneumococcal infection and during skin
      inflammation. Here, we propose a new way to specifically analyze IL-17-producing
      Vgamma6/Vdelta1(+) T cells based on the level of CD3 signals. Using this gating
      strategy, our data reinforce the crucial role of this gammadelta T-cell subset in
      respiratory and skin disorders. 

PMID- 25385070
TI  - The overproduction of 2,4-DTBP accompanying to the lack of available form of
      phosphorus during the biodegradative utilization of aminophosphonates by
      Aspergillus terreus.
AB  - Although information about the ability of some filamentous fungi to biodegrade
      organophosphonates is available, the knowledge about accompanying changes in
      fungal metabolism is very limited. The aim of our study was to determine the
      utilization of the chosen, structurally diverse aminophosphonates by Aspergillus
      terreus (Thom), in the context of the behaviour of this fungus while growing in
      unfavourable conditions, namely the lack of easily available phosphates. We found
      that all the studied compounds were utilized by fungus as nutritive sources of
      phosphorus, however, their effect on the production of fungal biomass depended on
      their structure. We also observed an interesting change in the metabolism of A.
      terreus; namely the overproduction of 2,4-di-tert-butylphenol (2,4-DTBP), which
      is known to possess fungistatic activity. In the case of our study, the
      biosynthesis of this compound was induced by phosphorus starvation, caused either
      by the lack of that element in the medium, or the poor degradation of
      phosphonate. 

PMID- 25385072
TI  - Micro-laparoscopic colectomy: initial experience.
AB  - INTRODUCTION: Single-port surgery (SPS) has been growing in acceptance as an
      alternative to traditional laparoscopic surgery. With SPS, there are technical
      skills required that are not routine to standard laparoscopy. We explored the
      feasibility of micro-laparoscopic colectomy (MLC) using 3 mm instruments in
      patients eligible for standard laparoscopic surgery. METHODS: We performed an IRB
      approved retrospective review of all segmental colectomy performed by a single
      surgeon in selected patients using a micro-laparoscopic technique. We utilized
      two 3-mm trocars and one 12-mm Hasson umbilical incision, which was later widen
      for specimen extraction. RESULTS: Eighty patients underwent MLC: Twenty-six for
      diverticulitis, 26 for cancer, 22 for polyps, 3 for Crohn's disease, and 3 for
      volvulus. Eight patients were converted into either laparotomy or hand port (10
      %) and three patients required the addition of one 5-mm trocar. Mean final
      extraction incision length was 3.9 cm. In cancer patients, the average lymph node
      harvest was 26 (range 13-70). The 30-day mortality was zero and the anastomotic
      leak rate was 1.3 %. CONCLUSIONS: MLC is safe and feasible when performing colon
      resections for benign and oncologic pathology. Extraction incision length is
      small and offers similar cosmesis to SPS without the steep learning curve needed
      to learn this technique.

PMID- 25385073
TI  - Erratum to: Duodenum-Stomach Anastomosis: a New Technique for Exocrine Drainage
      in Pancreas Transplantation.

PMID- 25385071
TI  - Protein interaction module-assisted function X (PIMAX) approach to producing
      challenging proteins including hyperphosphorylated tau and active CDK5/p25 kinase
      complex.
AB  - Many biomedically critical proteins are underrepresented in proteomics and
      biochemical studies because of the difficulty of their production in Escherichia
      coli. These proteins might possess posttranslational modifications vital to their
      functions, tend to misfold and be partitioned into bacterial inclusion bodies, or
      act only in a stoichiometric dimeric complex. Successful production of these
      proteins requires efficient interaction between these proteins and a specific
      "facilitator," such as a protein-modifying enzyme, a molecular chaperone, or a
      natural physical partner within the dimeric complex. Here we report the design
      and application of a protein interaction module-assisted function X (PIMAX)
      system that effectively overcomes these hurdles. By fusing two proteins of
      interest to a pair of well-studied protein-protein interaction modules, we were
      able to potentiate the association of these two proteins, resulting in successful
      production of an enzymatically active cyclin-dependent kinase complex and
      hyperphosphorylated tau protein, which is intimately linked to Alzheimer disease.
      Furthermore, using tau isoforms quantitatively phosphorylated by GSK-3beta and
      CDK5 kinases via PIMAX, we demonstrated the hyperphosphorylation-stimulated tau
      oligomerization in vitro, paving the way for new Alzheimer disease drug
      discoveries. Vectors for PIMAX can be easily modified to meet the needs of
      different applications. This approach thus provides a convenient and modular
      suite with broad implications for proteomics and biomedical research. 

PMID- 25385075
TI  - Comparison of facial predilection sites for cutaneous squamous cell carcinoma and
      actinic keratosis in Japanese patients.
AB  - Cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK) occur most
      often on the face. Ultraviolet light is apparently their most common cause. As AK
      is considered to be a precursor of cSCC, their distribution on the face should be
      similar. However, cSCC often occurs on the temple or mandibular area, whereas AK
      arises on the central forehead, cheek or nose. We retrospectively evaluated
      differences in affected site distribution for cSCC (n = 54) and AK (n = 95). We
      found AK to occur preferentially on the central facial area (63/95, 66%), which
      is the most sun-exposed area, and cSCC to occur preferentially on peripheral
      areas such as the temple and mandibular area (24/54, 44%). Those distributions
      were significantly different (P = 0.011, Fisher's exact test). This result
      suggests that cSCC occurs preferentially in the peripheral area compared with the
      central facial area, which further implies that either other factors are needed
      to make AK progress to cSCC in peripheral areas, or that peripheral cSCC can
      occur without preceding AK. This is the first report to focus on geographic
      assessment of cSCC and AK in detail. Further studies are needed to elucidate the
      mechanism of our finding. 

PMID- 25385074
TI  - Lobular breast cancers lack the inverse relationship between ER/PR status and
      cell growth rate characteristic of ductal cancers in two independent patient
      cohorts: implications for tumor biology and adjuvant therapy.
AB  - BACKGROUND: Although invasive lobular carcinoma (ILC) of the breast differs from
      invasive ductal carcinoma (IDC) in numerous respects - including its genetics,
      clinical phenotype, metastatic pattern, and chemosensitivity - most experts
      continue to manage ILC and IDC identically in the adjuvant setting. Here we
      address this discrepancy by comparing early-stage ILC and IDC in two breast
      cancer patient cohorts of differing nationality and ethnicity. METHODS: The
      clinicopathologic features of 2029 consecutive breast cancer patients diagnosed
      in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between
      tumor histology and other clinicopathologic variables, including ER/PR and Ki67,
      were analysed. RESULTS: Two hundred thirty-nine patients were identified with ILC
      (11.8%) and 1790 patients with IDC. AUS patients were older (p <0.001) and more
      often postmenopausal (p <0.03) than HK patients. As expected, ILC tumors were
      lower in grade and proliferative rate, and more often ER-positive and HER2
      negative, than IDC (p <0.002); yet despite this, ILC tumors were as likely as IDC
      to present with nodal metastases (p >0.7). Moreover, whereas IDC tumors exhibited
      a strongly negative relationship between ER/PR and Ki67 status (p <0.0005), ILC
      tumors failed to demonstrate any such inverse relationship (p >0.6). CONCLUSION:
      These data imply that the primary adhesion defect in ILC underlies a secondary
      stromal-epithelial disconnect between hormonal signaling and tumor growth,
      suggesting in turn that this peritumoral feedback defect could reduce both the
      antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic
      therapies for such tumors. Hence, we caution against assuming similar adjuvant
      chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and
      Ki67, whether based on immunohistochemical or gene expression assays.

PMID- 25385076
TI  - Decision making for life sustaining therapies in pediatric intensive care: who
      should decide?

PMID- 25385077
TI  - Attribution of movement: Potential links between subjective reports of agency and
      output monitoring.
AB  - According to agency memory theory, individuals decide whether "I did it" based on
      a memory trace of "I am doing it". The purpose of this study was to validate the
      agency memory theory. To this end, several hand actions were individually
      presented as samples, and participants were asked to perform the sample action,
      observe the performance of that action by another person, or imagine performing
      the action. Online feedback received by the participants during the action was
      manipulated among the different conditions, and output monitoring, in which
      participants were asked whether they had performed each hand action, was
      conducted. The rate at which respondents thought that they themselves had
      performed the action was higher when visual feedback was unaltered than when it
      was altered (Experiment 1A), and this tendency was observed across all types of
      altered feedback (Experiment 1B). The observation of an action performed by the
      hand of another person did not increase the rate at which respondents thought
      that they themselves had performed the action unless the participants actually
      did perform the action (Experiments 2A and 2B). In Experiment 3, a relationship
      was observed between the subjective feeling that "I am the one who is causing an
      action" and the memory that "I did perform the action". These experiments support
      the hypothesis that qualitative information and sense of "self" are tagged in a
      memory trace and that such tags can be used as cues for judgements when the
      memory is related to the "self". 

PMID- 25385078
TI  - PIERO ontology for analysis of biochemical transformations: effective
      implementation of reaction information in the IUBMB enzyme list.
AB  - Genomics is faced with the issue of many partially annotated putative enzyme
      encoding genes for which activities have not yet been verified, while
      metabolomics is faced with the issue of many putative enzyme reactions for which
      full equations have not been verified. Knowledge of enzymes has been collected by
      IUBMB, and has been made public as the Enzyme List. To date, however, the
      terminology of the Enzyme List has not been assessed comprehensively by
      bioinformatics studies. Instead, most of the bioinformatics studies simply use
      the identifiers of the enzymes, i.e. the Enzyme Commission (EC) numbers. We
      investigated the actual usage of terminology throughout the Enzyme List, and
      demonstrated that the partial characteristics of reactions cannot be retrieved by
      simply using EC numbers. Thus, we developed a novel ontology, named PIERO, for
      annotating biochemical transformations as follows. First, the terminology
      describing enzymatic reactions was retrieved from the Enzyme List, and was
      grouped into those related to overall reactions and biochemical transformations.
      Consequently, these terms were mapped onto the actual transformations taken from
      enzymatic reaction equations. This ontology was linked to Gene Ontology (GO) and
      EC numbers, allowing the extraction of common partial reaction characteristics
      from given sets of orthologous genes and the elucidation of possible enzymes from
      the given transformations. Further future development of the PIERO ontology
      should enhance the Enzyme List to promote the integration of genomics and
      metabolomics. 

PMID- 25385079
TI  - Implementing a modeling software for animated protein-complex interactions using
      a physics simulation library.
AB  - To better understand the behaviors and structural dynamics of proteins within a
      cell, novel software tools are being developed that can create molecular
      animations based on the findings of structural biology. This study proposes our
      method developed based on our prototypes to detect collisions and examine the
      soft-body dynamics of molecular models. The code was implemented with a software
      development toolkit for rigid-body dynamics simulation and a three-dimensional
      graphics library. The essential functions of the target software system included
      the basic molecular modeling environment, collision detection in the molecular
      models, and physical simulations of the movement of the model. Taking advantage
      of recent software technologies such as physics simulation modules and
      interpreted scripting language, the functions required for accurate and
      meaningful molecular animation were implemented efficiently. 

PMID- 25385080
TI  - ReSAPP: predicting overlapping protein complexes by merging multiple-sampled
      partitions of proteins.
AB  - Many proteins are known to perform their own functions when they form particular
      groups of proteins, called protein complexes. With the advent of large-scale
      protein-protein interaction (PPI) studies, it has been a challenging problem in
      systems biology to predict protein complexes from PPIs. In this paper, we propose
      a novel method, called Repeated Simulated Annealing of Partitions of Proteins
      (ReSAPP), which predicts protein complexes from weighted PPIs. ReSAPP, in the
      first stage, generates multiple (possibly different) partitions of all proteins
      of given PPIs by repeatedly applying a simulated annealing based optimization
      algorithm to the PPIs. In the second stage, all different clusters of size two or
      more in those multiple partitions are merged into a collection of those clusters,
      which are outputted as predicted protein complexes. In performance comparison of
      ReSAPP with our previous algorithm, PPSampler2, as well as other various tools,
      MCL, MCODE, DPClus, CMC, COACH, RRW, NWE, and PPSampler1, ReSAPP is shown to
      outperform the other methods. Furthermore, the value of F-measure of ReSAPP is
      higher than that of the variant of ReSAPP without merging partitions. Thus, we
      empirically conclude that the combination of sampling multiple partitions and
      merging them is effective to predict protein complexes. 

PMID- 25385081
TI  - Supervised learning method for predicting chromatin boundary associated insulator
      elements.
AB  - In eukaryotic cells, the DNA material is densely packed inside the nucleus in the
      form of a DNA-protein complex structure called chromatin. Since the actual
      conformation of the chromatin fiber defines the possible regulatory interactions
      between genes and their regulatory elements, it is very important to understand
      the mechanisms governing folding of chromatin. In this paper, we show that
      supervised methods for predicting chromatin boundary elements are much more
      effective than the currently popular unsupervised methods. Using boundary
      locations from published Hi-C experiments and modEncode tracks as features, we
      can tell the insulator elements from randomly selected background sequences with
      great accuracy. In addition to accurate predictions of the training boundary
      elements, our classifiers make new predictions. Many of them correspond to the
      locations of known insulator elements. The key features used for predicting
      boundary elements do not depend on the prediction method. Because of its
      miniscule size, chromatin state cannot be measured directly, we need to rely on
      indirect measurements, such as ChIP-Seq and fill in the gaps with computational
      models. Our results show that currently, at least in the model organisms, where
      we have many measurements including ChIP-Seq and Hi-C, we can make accurate
      predictions of insulator positions. 

PMID- 25385082
TI  - Discovering novel protein-protein interactions by measuring the protein semantic
      similarity from the biomedical literature.
AB  - Protein-protein interactions (PPIs) are involved in the majority of biological
      processes. Identification of PPIs is therefore one of the key aims of biological
      research. Although there are many databases of PPIs, many other unidentified PPIs
      could be buried in the biomedical literature. Therefore, automated identification
      of PPIs from biomedical literature repositories could be used to discover
      otherwise hidden interactions. Search engines, such as Google, have been
      successfully applied to measure the relatedness among words. Inspired by such
      approaches, we propose a novel method to identify PPIs through semantic
      similarity measures among protein mentions. We define six semantic similarity
      measures as features based on the page counts retrieved from the MEDLINE
      database. A machine learning classifier, Random Forest, is trained using the
      above features. The proposed approach achieve an averaged micro-F of 71.28% and
      an averaged macro-F of 64.03% over five PPI corpora, an improvement over the
      results of using only the conventional co-occurrence feature (averaged micro-F of
      68.79% and an averaged macro-F of 60.49%). A relation-word reinforcement further
      improves the averaged micro-F to 71.3% and averaged macro-F to 65.12%. Comparing
      the results of the current work with other studies on the AIMed corpus (ranging
      from 77.58% to 85.1% in micro-F, 62.18% to 76.27% in macro-F), we show that the
      proposed approach achieves micro-F of 81.88% and macro-F of 64.01% without the
      use of sophisticated feature extraction. Finally, we manually examine the newly
      discovered PPI pairs based on a literature review, and the results suggest that
      our approach could extract novel protein-protein interactions. 

PMID- 25385083
TI  - PRIGSA: protein repeat identification by graph spectral analysis.
AB  - Repetition of a structural motif within protein is associated with a wide range
      of structural and functional roles. In most cases the repeating units are well
      conserved at the structural level while at the sequence level, they are mostly
      undetectable suggesting the need for structure-based methods. Since most known
      methods require a training dataset, de novo approach is desirable. Here, we
      propose an efficient graph-based approach for detecting structural repeats in
      proteins. In a protein structure represented as a graph, interactions between
      inter- and intra-repeat units are well captured by the eigen spectra of adjacency
      matrix of the graph. These conserved interactions give rise to similar
      connections and a unique profile of the principal eigen spectra for each
      repeating unit. The efficacy of the approach is shown on eight repeat families
      annotated in UniProt, comprising of both solenoid and nonsolenoid repeats with
      varied secondary structure architecture and repeat lengths. The performance of
      the approach is also tested on other known benchmark datasets and the performance
      compared with two repeat identification methods. For a known repeat type, the
      algorithm also identifies the type of repeat present in the protein. A web tool
      implementing the algorithm is available at the URL
      http://bioinf.iiit.ac.in/PRIGSA/.

PMID- 25385084
TI  - An effective differential expression analysis of deep-sequencing data based on
      the Poisson log-normal model.
AB  - Tremendous amount of deep-sequencing data has unprecedentedly improved our
      understanding in biomedical science by digital sequence reads. To mine useful
      information from such data, a proper distribution for modeling all range of the
      count data and accurate parameter estimation are required. In this paper, we
      propose a method, called "DEPln," for differential expression analysis based on
      the Poisson log-normal (PLN) distribution with an accurate parameter estimation
      strategy, which aims to overcome the inconvenience in the mathematical analysis
      of the traditional PLN distribution. The performance of our proposed method is
      validated by both synthetic and real data. Experimental results indicate that our
      method outperforms the traditional methods in terms of the discrimination ability
      and results in a good tradeoff between the recall rate and the precision. Thus,
      our work provides a new approach for gene expression analysis and has strong
      potential in deep-sequencing based research. 

PMID- 25385085
TI  - Synchrotron X-ray microtomography of xylem embolism in Sequoia sempervirens
      saplings during cycles of drought and recovery.
AB  - The formation of emboli in xylem conduits can dramatically reduce hydraulic
      capacity and represents one of the principal mechanisms of drought-induced
      mortality in woody plants. However, our understanding of embolism formation and
      repair is constrained by a lack of tools to directly and nondestructively measure
      these processes at high spatial resolution. Using synchrotron-based microcomputed
      tomography (microCT), we examined embolism in the xylem of coast redwood (Sequoia
      sempervirens) saplings that were subjected to cycles of drought and rewatering.
      Embolism formation was observed occurring by three different mechanisms: as
      tracheids embolizing in wide tangential bands; as isolated tracheids in seemingly
      random events; and as functional groups connected to photosynthetic organs. Upon
      rewatering, stem water potential recovered to predrought stress levels within 24
      h; however, no evidence of embolism repair was observed even after a further 2 wk
      under well-watered conditions. The results indicate that intertracheid air
      seeding is the primary mechanism by which embolism spreads in the xylem of S.
      sempervirens, but also show that a small number of tracheids initially become gas
      filled via another mechanism. The inability of S. sempervirens saplings to
      reverse drought-induced embolism is likely to have important ecological impacts
      on this species. 

PMID- 25385086
TI  - Can Payers Use Prices to Improve Quality? Evidence from English Hospitals.
AB  - In most activity-based financing systems, payers set prices reactively based on
      historical averages of hospital reported costs. If hospitals respond to prices,
      payers might set prices proactively to affect the volume of particular treatments
      or clinical practice. We evaluate the effects of a unique initiative in England
      in which the price offered to hospitals for discharging patients on the same day
      as a particular procedure was increased by 24%, while the price for inpatient
      treatment remained unchanged. Using national hospital records for 205,784
      patients admitted for the incentivised procedure and 838,369 patients admitted
      for a range of non-incentivised procedures between 1 December 2007 and 31 March
      2011, we consider whether this price change had the intended effect and/or
      produced unintended effects. We find that the price change led to an almost six
      percentage point increase in the daycase rate and an 11 percentage point increase
      in the planned daycase rate. Patients benefited from a lower proportion of
      procedures reverted to open surgery during a planned laparoscopic procedure and
      from a reduction in long stays. There was no evidence that readmission and death
      rates were affected. The results suggest that payers can set prices proactively
      to incentivise hospitals to improve quality.

PMID- 25385087
TI  - An anti CuO2-type metal hydride square net structure in Ln2M2As2H(x) (Ln=La or
      Sm, M=Ti, V, Cr, or Mn).
AB  - Using a high pressure technique and the strong donating nature of H(-), a new
      series of tetragonal La2Fe2Se2O3-type layered mixed-anion arsenides,
      Ln2M2As2H(x), was synthesized (Ln=La or Sm, M=Ti, V, Cr, or Mn; x~3). In these
      compounds, an unusual M2H square net, which has anti CuO2 square net structures
      accompanying two As(3-) ions, is sandwiched by (LaH)2 fluorite layers. Notably,
      strong metal-metal bonding with a distance of 2.80 A was confirmed in
      La2Ti2As2H2.3, which has metallic properties. In fact, these compounds are
      situated near the boundary between salt-like ionic hydrides and transition-metal
      hydrides with metallic characters.

PMID- 25385088
TI  - A new structural insight into XPA-DNA interactions.
AB  - XPA (xeroderma pigmentosum group A) protein is an essential factor for NER
      (nucleotide excision repair) which is believed to be involved in DNA damage
      recognition/verification, NER factor recruiting and stabilization of repair
      intermediates. Past studies on the structure of XPA have focused primarily on XPA
      interaction with damaged DNA. However, how XPA interacts with other DNA
      structures remains unknown though recent evidence suggest that these structures
      could be important for its roles in both NER and non-NER activities. Previously,
      we reported that XPA recognizes undamaged DNA ds/ssDNA (double-strand/single
      strandDNA) junctions with a binding affinity much higher than its ability to bind
      bulky DNA damage. To understand how this interaction occurs biochemically we
      implemented a structural determination of the interaction using a MS-based
      protein footprinting method and limited proteolysis. By monitoring surface
      accessibility of XPA lysines to NHS-biotin modification in the free protein and
      the DNA junction-bound complex we show that XPA physically interacts with the DNA
      junctions via two lysines, K168 and K179, located in the previously known XPA(98
      219) DBD (DNA-binding domain). Importantly, we also uncovered new lysine
      residues, outside of the known DBD, involved in the binding. We found that
      residues K221, K222, K224 and K236 in the C-terminal domain are involved in DNA
      binding. Limited proteolysis analysis of XPA-DNA interactions further confirmed
      this observation. Structural modelling with these data suggests a clamp-like DBD
      for the XPA binding to ds/ssDNA junctions. Our results provide a novel structure
      function view of XPA-DNA junction interactions. 

PMID- 25385089
TI  - Imaging techniques to evaluate cell therapy in peripheral artery disease: state
      of the art and clinical trials.
AB  - Cell-based therapies, as potential approach to cure peripheral artery disease
      (PAD), have been clinically investigated after promising results in preclinical
      models. The so far published studies are very heterogeneous, as different cell
      sources, cell types, amounts of administered cells and delivering strategies have
      been used. Overall, cell therapies for PAD bring about a general improvement of
      patient's clinical condition, even though conclusions cannot be established due
      to the small size and non-randomized design of these trials. In this context, non
      invasive imaging techniques, aimed to monitor angiogenesis and neovascularization
      after cell therapy, will help the follow-up of clinical studies. However, still
      much work is needed to establish advanced imaging procedure to overcome the
      limitation of the current techniques and to accumulate more data in large
      populations of patients. Here, we report the main imaging techniques employed to
      evaluate the outcome of the different cell-based therapies in PAD. Moreover, we
      focus on both published and ongoing clinical trials utilizing cell therapy in
      PAD. 

PMID- 25385090
TI  - Examining Pre-migration Health Among Filipino Nurses.
AB  - The healthy immigrant hypothesis asserts that immigrants arrive in the receiving
      country healthier than same race/ethnic counterparts born there. Contemporary
      research, however, has not evaluated pre-migration health among migrants, nor has
      explicitly considered comparisons with non-migrants in the country of origin. Pre
      migration health was examined among 621 Filipino nurses, including self-reported
      physical health, mental health, health behaviors, and social stress. Measures
      were compared by intention to migrate and also tested as predictors of actual
      migration using time-to-event analysis. Nurses intending to migrate had higher
      proportion of depression and reported higher general perceived stress compared to
      those not. Predictors of actual migration included age, mentally unhealthy days,
      social strain, and social support. Physical health and health behavior measures
      had no association with migration intention or actual migration. Findings suggest
      that, relative to those not intending to migrate, nurses intending to migrate
      have worse mental health status and social stress; and, do not have a physical
      health advantage. Future research must span the pre- to post-migration continuum
      to better understand the impact of moving from one country to another on health
      and well-being. 

PMID- 25385091
TI  - Effect of the novel BKCa channel opener LDD175 on the modulation of corporal
      smooth muscle tone.
AB  - INTRODUCTION: The BKCa channel has been reported to play an important role in
      erectile function. Recently, novel BKCa channel activator, LDD175, was
      introduced. AIM: This study aims to investigate whether LDD175 relaxes corporal
      smooth muscle (CSM) via BKCa channel activation. METHODS: After isolation of CSM
      strip from a male rabbit model, contraction studies using organ bath was
      performed. Isolating human tissue and cell cultures, electrophysiological studies
      were done via whole-cell patch-clamp recording. MAIN OUTCOME MEASURES:
      Vasodilatory effects of LDD175 were evaluated by cumulative addition ranging from
      10(-7) to 10(-4) M in corpus cavernosal strips after precontraction with 10(-5) M
      phenylephrine via organ bath system. Using cultured human CSM cells, patch-clamp
      recording was performed. Erectile function was measured by in vivo rat cavernous
      nerve stimulation. RESULTS: LDD175 caused an endothelium-independent relaxation
      of corporal tissues, and this effect was abolished by pretreatment with
      iberiotoxin. The relaxation effect of 10(-4) M LDD175 was greater than that of
      10(-6) M udenafil (54.0 +/- 3.1% vs. 34.5 +/- 3.9%, P < 0.05); 10(-5) M LDD175
      with 10(-6) M udenafil caused a greater relaxation effect on strips than 10(-5) M
      LDD175 or 10(-6) M udenafil alone (50.7%, 34.1%, vs. 20.7%, respectively, P <
      0.001). In patch-clamp recordings, LDD175 increased K(+) currents in a dose
      dependent manner, and washout of LDD175 or the addition of iberiotoxin fully
      reversed the increase. Intravenous LDD175 improved erectile function measured by
      area under the curve (AUC) of the intracavernosal pressure (ICP)/arterial blood
      pressure (ABP) ratio (1,612.1 +/- 135.6 vs. 1,093.7 +/- 123.1, P < 0.05). There
      was no difference between 10 mg/kg LDD175 and 1 mg/kg udenafil regarding maximal
      ICP, maximal ICP/ABP ratio, and the AUC of the ICP/ABP ratio (P > 0.05).
      CONCLUSIONS: LDD175 leads to an endothelium-independent relaxation of erectile
      tissue, primarily through the opening of BKCa channels. The results suggest that
      LDD175 might be a new candidate treatment for erectile dysfunction.

PMID- 25385093
TI  - Application of the Hyper-Poisson Generalized Linear Model for Analyzing Motor
      Vehicle Crashes.
AB  - The hyper-Poisson distribution can handle both over- and underdispersion, and its
      generalized linear model formulation allows the dispersion of the distribution to
      be observation-specific and dependent on model covariates. This study's objective
      is to examine the potential applicability of a newly proposed generalized linear
      model framework for the hyper-Poisson distribution in analyzing motor vehicle
      crash count data. The hyper-Poisson generalized linear model was first fitted to
      intersection crash data from Toronto, characterized by overdispersion, and then
      to crash data from railway-highway crossings in Korea, characterized by
      underdispersion. The results of this study are promising. When fitted to the
      Toronto data set, the goodness-of-fit measures indicated that the hyper-Poisson
      model with a variable dispersion parameter provided a statistical fit as good as
      the traditional negative binomial model. The hyper-Poisson model was also
      successful in handling the underdispersed data from Korea; the model performed as
      well as the gamma probability model and the Conway-Maxwell-Poisson model
      previously developed for the same data set. The advantages of the hyper-Poisson
      model studied in this article are noteworthy. Unlike the negative binomial model,
      which has difficulties in handling underdispersed data, the hyper-Poisson model
      can handle both over- and underdispersed crash data. Although not a major issue
      for the Conway-Maxwell-Poisson model, the effect of each variable on the expected
      mean of crashes is easily interpretable in the case of this new model. 

PMID- 25385092
TI  - Mitochondrial injury and dysfunction in hypertension-induced cardiac damage.
AB  - Hypertension remains an important modifiable risk factor for cardiovascular
      disease, associated with increased morbidity and mortality. Deciphering the
      mechanisms involved in the pathogenesis of hypertension is critical, as its
      prevalence continues increasing worldwide. Mitochondria, the primary cellular
      energy producers, are numerous in parenchymal cells of the heart, kidney, and
      brain, major target organs in hypertension. These membrane-bound organelles not
      only maintain cellular respiration but also modulate several functions of the
      cell including proliferation, apoptosis, generation of reactive oxygen species,
      and intracellular calcium homeostasis. Therefore, mitochondrial damage and
      dysfunction compromise overall cell functioning. In recent years, significant
      advances increased our understanding of mitochondrial morphology, bioenergetics,
      and homeostasis, and in turn of their role in several diseases, so that
      mitochondrial abnormalities and dysfunction have been identified in experimental
      models of hypertension. In this review, we summarize current knowledge of the
      contribution of dysfunctional mitochondria to the pathophysiology of hypertension
      induced cardiac damage, as well as available evidence of mitochondrial injury
      induced damage in other organs. Finally, we discuss the capability of
      antihypertensive therapy to ameliorate hypertensive mitochondrial injury, and the
      potential position of mitochondria as therapeutic targets in patients with
      hypertension. 

PMID- 25385094
TI  - Effect of steady-state faldaprevir on the pharmacokinetics of steady-state
      methadone and buprenorphine-naloxone in subjects receiving stable addiction
      management therapy.
AB  - The effects of steady-state faldaprevir on the safety, pharmacokinetics, and
      pharmacodynamics of steady-state methadone and buprenorphine-naloxone were
      assessed in 34 healthy male and female subjects receiving stable addiction
      management therapy. Subjects continued receiving a stable oral dose of either
      methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up
      to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240
      mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood
      samples were taken for pharmacokinetic analysis. The pharmacodynamics of the
      opioid maintenance regimens were evaluated by the objective and subjective opioid
      withdrawal scales. Coadministration of faldaprevir with methadone or
      buprenorphine-naloxone resulted in geometric mean ratios for the steady-state
      area under the concentration-time curve from 0 to 24 h (AUC(0-24,ss)), the steady
      state maximum concentration of the drug in plasma (C(max,ss)), and the steady
      state concentration of the drug in plasma at 24 h (C(24,ss)) of 0.92 to 1.18 for
      (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with
      90% confidence intervals including, or very close to including, 1.00 (no effect),
      suggesting a limited overall effect of faldaprevir. Although individual data
      showed moderate variability in the exposures between subjects and treatments,
      there was no evidence of symptoms of opiate overdose or withdrawal either during
      the coadministration of faldaprevir with methadone or buprenorphine-naloxone or
      after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed
      in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion,
      faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine
      naloxone without dose adjustment, although given the relatively narrow
      therapeutic windows of these agents, monitoring for opiate overdose and
      withdrawal may still be appropriate. (This study has been registered at
      ClinicalTrials.gov under registration no. NCT01637922.).

PMID- 25385095
TI  - Contribution of clinically derived mutations in ERG11 to azole resistance in
      Candida albicans.
AB  - In Candida albicans, the ERG11 gene encodes lanosterol demethylase, the target of
      the azole antifungals. Mutations in ERG11 that result in an amino acid
      substitution alter the abilities of the azoles to bind to and inhibit Erg11,
      resulting in resistance. Although ERG11 mutations have been observed in clinical
      isolates, the specific contributions of individual ERG11 mutations to azole
      resistance in C. albicans have not been widely explored. We sequenced ERG11 in 63
      fluconazole (FLC)-resistant clinical isolates. Fifty-five isolates carried at
      least one mutation in ERG11, and we observed 26 distinct positions in which amino
      acid substitutions occurred. We mapped the 26 distinct variant positions in these
      alleles to four regions in the predicted structure for Erg11, including its
      predicted catalytic site, extended fungus-specific external loop, proximal
      surface, and proximal surface-to-heme region. In total, 31 distinct ERG11 alleles
      were recovered, with 10 ERG11 alleles containing a single amino acid
      substitution. We then characterized 19 distinct ERG11 alleles by introducing them
      into the wild-type azole-susceptible C. albicans SC5314 strain and testing them
      for susceptibilities to FLC, itraconazole (ITC), and voriconazole (VRC). The
      strains that were homozygous for the single amino acid substitutions Y132F,
      K143R, F145L, S405F, D446E, G448E, F449V, G450E, and G464S had a >= 4-fold
      increase in FLC MIC. The strains that were homozygous for several double amino
      acid substitutions had decreased azole susceptibilities beyond those conferred by
      any single amino acid substitution. These findings indicate that mutations in
      ERG11 are prevalent among azole-resistant clinical isolates and that most
      mutations result in appreciable changes in FLC and VRC susceptibilities.

PMID- 25385096
TI  - Pharmacokinetic interactions between primaquine and pyronaridine-artesunate in
      healthy adult Thai subjects.
AB  - Pyronaridine-artesunate is a newly introduced artemisinin-based combination
      treatment which may be deployed together with primaquine. A single-dose,
      randomized, three-sequence crossover study was conducted in healthy Thai
      volunteers to characterize potential pharmacokinetic interactions between these
      drugs. Seventeen healthy adults received a single oral dose of primaquine alone
      (30 mg base) and were then randomized to receive pyronaridine-artesunate alone
      (540-180 mg) or pyronaridine-artesunate plus primaquine in combination, with
      intervening washout periods between all treatments. The pharmacokinetic
      properties of primaquine, its metabolite carboxyprimaquine, artesunate, its
      metabolite dihydroartemisinin, and pyronaridine were assessed in 15 subjects
      using a noncompartmental approach followed by a bioequivalence evaluation. All
      drugs were well tolerated. The single oral dose of primaquine did not result in
      any clinically relevant pharmacokinetic alterations to pyronaridine, artesunate,
      or dihydroartemisinin exposures. There were significantly higher primaquine
      maximum plasma drug concentrations (geometric mean ratio, 30%; 90% confidence
      interval [CI], 17% to 46%) and total exposures (15%; 6.4% to 24%) during
      coadministration with pyronaridine-artesunate than when primaquine was given
      alone. Pyronaridine, like chloroquine and piperaquine, increases plasma
      primaquine concentrations. (This study has been registered at ClinicalTrials.gov
      under registration no. NCT01552330.). 

PMID- 25385097
TI  - Molecular characterization of fluoroquinolone resistance in nontypeable
      Haemophilus influenzae clinical isolates.
AB  - Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory
      infections in adults, who are frequently treated with fluoroquinolones. The aims
      of this study were to characterize the genotypes of fluoroquinolone-resistant
      NTHi isolates and their mechanisms of resistance. Among 7,267 H. influenzae
      isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were
      ciprofloxacin resistant according to Clinical and Laboratory Standards Institute
      (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013
      detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic
      acid resistant. Sequencing of their quinolone resistance-determining regions and
      genotyping by pulse-field gel electrophoresis and multilocus sequence typing of
      the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid
      resistant isolates were performed. In the NTHi isolates studied, two mutations
      producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues
      (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with
      one or two mutations (n = 15) had ciprofloxacin and levofloxacin MICs of 0.12 to
      2 MUg/ml, while those with three or more mutations (n = 15) had MICs of 4 to 16
      MUg/ml. Long persistence of fluoroquinolone-resistant strains was observed in
      three chronic obstructive pulmonary disease patients. High genetic diversity was
      observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones
      are commonly used to treat respiratory infections, the proportion of resistant
      NTHi isolates remains low. The nalidixic acid disk test is useful for detecting
      the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible
      strains that are at a potential risk for the development of resistance under
      selective pressure by fluoroquinolone treatment. 

PMID- 25385098
TI  - Enhanced efficacy of cidofovir combined with vaccinia immune globulin in treating
      progressive cutaneous vaccinia virus infections in immunosuppressed hairless
      mice.
AB  - The treatment of progressive vaccinia in individuals has involved antiviral
      drugs, such as cidofovir (CDV), brincidofovir, and/or tecovirimat, combined with
      vaccinia immune globulin (VIG). VIG is costly, and its supply is limited, so
      sparing the use of VIG during treatment is an important objective. VIG sparing
      was modeled in immunosuppressed mice by maximizing the treatment benefits of CDV
      combined with VIG to determine the effective treatments that delayed the time to
      death, reduced cutaneous lesion severity, and/or decreased tissue viral titers.
      SKH-1 hairless mice immunosuppressed with cyclophosphamide and hairless SCID mice
      (SHO strain) were infected cutaneously with vaccinia virus. Monotherapy, dual
      combinations (CDV plus VIG), or triple therapy (topical CDV, parenteral CDV, and
      VIG) were initiated 2 days postinfection and were given every 3 to 4 days through
      day 11. The efficacy assessment included survival rate, cutaneous lesion
      severity, and viral titers. Delays in the time to death and the reduction in
      lesion severity occurred in the following order of efficacy: triple therapy had
      greater efficacy than double combinations (CDV plus VIG or topical plus
      parenteral CDV), which had greater efficacy than VIG alone. Parenteral
      administration of CDV or VIG was necessary to suppress virus titers in internal
      organs (liver, lung, and spleen). The skin viral titers were significantly
      reduced by triple therapy only. The greatest efficacy was achieved by triple
      therapy. In humans, this regimen should translate to a faster cure rate, thus
      sparing the amount of VIG used for treatment. 

PMID- 25385099
TI  - Effect of the hepatitis C virus protease inhibitor faldaprevir on the
      pharmacokinetics of an oral contraceptive containing ethinylestradiol and
      levonorgestrel in healthy female volunteers.
AB  - Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor.
      Faldaprevir is known to inhibit P-glycoprotein, CYP3A4, and UDP
      glucuronosyltransferase 1A1. This study evaluated the effect of steady-state 240
      mg faldaprevir on the pharmacokinetics (PK) of an oral contraceptive containing
      ethinylestradiol (EE) and levonorgestrel (LNG) in healthy premenopausal women. In
      period 1, subjects received EE/LNG once daily (QD) for 14 days. Blood samples
      were taken on days 1, 11, and 12, with intensive PK blood sampling for EE and LNG
      on day 13. In period 2, subjects received EE-LNG QD and 240 mg faldaprevir QD on
      days 14 to 21 (240 mg faldaprevir twice daily on day 14). Blood samples were
      taken on days 14, 19, and 20, with PK profiling samples obtained for EE and LNG
      on day 21. A total of 15/16 subjects completed the study. Overall, EE and LNG
      exposure (assessed by the area under the curve) was approximately 1.4-fold higher
      when EE and LNG were coadministered with faldaprevir than when administered
      alone. Median t1/2 (terminal half-life in plasma at steady state) values were
      prolonged for both EE (2.4 h longer) and LNG (4.7 h longer) when EE and LNG were
      coadministered with faldaprevir. The mean oral clearance and apparent volume of
      distribution of both EE and LNG were lower (~ 30%) when EE and LNG were
      coadministered with faldaprevir. Coadministration of faldaprevir and an oral
      contraceptive resulted in a moderate increase in exposure to both EE and LNG.
      However, this increase was not considered clinically meaningful, and no dose
      adjustment of oral contraceptives was deemed necessary. (This study has been
      registered at ClinicalTrials.gov under registration number NCT01570244.).

PMID- 25385100
TI  - Arthritis and benznidazole: more closely related than we thought.
AB  - Chagas disease is a parasitic infection that leads to a significant public health
      problem in countries where the disease is endemic and where it is nonendemic.
      Benznidazole is the most commonly used drug for the etiological treatment of
      Chagas disease. Patients treated with benznidazole suffer frequent adverse drug
      reactions. Although arthralgia is common, arthritis has been reported as a very
      rare side effect. The objective of this study was to describe arthritis in a
      cohort of Trypanosoma cruzi-infected patients treated with benznidazole. 

PMID- 25385101
TI  - Lack of neuropathological changes in rats administered tedizolid phosphate for
      nine months.
AB  - Tedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans
      rats by oral gavage once daily for up to 9 months at doses near the maximum
      tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma
      exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and
      30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were
      similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than
      exposures in patients at the therapeutic dose (200 mg once daily). Evaluated
      endpoints included survival, clinical observations, body weight, and food
      consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional
      observational batteries, and locomotor activity measures were conducted, brain
      weights/sizes were recorded, and perfusion-fixed tissues were collected from 12
      rats/sex/group/time point. A detailed morphological assessment was conducted on
      brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic,
      sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9
      months, less body weight gain was seen in high-dose males (-6.7%) and females (
      5.8%) compared with that seen in controls. There were no tedizolid-related
      adverse neurobehavioral effects or tedizolid-related histopathologic changes in
      the central/peripheral nervous systems, including the optic nerve. Results of
      this study indicate that tedizolid was not neurotoxic when administered long term
      to pigmented rats at doses near the MTD, which were up to 8-fold higher than the
      human therapeutic exposure. 

PMID- 25385102
TI  - Antiviral activity of a single-domain antibody immunotoxin binding to
      glycoprotein D of herpes simplex virus 2.
AB  - Despite years of research dedicated to preventing the sexual transmission of
      herpes simplex virus 2 (HSV-2), there is still no protective vaccine or
      microbicide against one of the most common sexually transmitted infections in the
      world. Using a phage display library constructed from a llama immunized with
      recombinant HSV-2 glycoprotein D, we identified a single-domain antibody VHH,
      R33, which binds to the viral surface glycoprotein D. Although R33 does not
      demonstrate any HSV-2 neutralization activity in vitro, when expressed with the
      cytotoxic domain of exotoxin A, the resulting immunotoxin (R33ExoA) specifically
      and potently kills HSV-2-infected cells, with a 50% neutralizing dilution (IC50)
      of 6.7 nM. We propose that R33ExoA could be used clinically to prevent
      transmission of HSV-2 through killing of virus-producing epithelial cells during
      virus reactivation. R33 could also potentially be used to deliver other cytotoxic
      effectors to HSV-2-infected cells. 

PMID- 25385103
TI  - In vitro antiviral activity and preclinical and clinical resistance profile of
      miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor
      miR-122.
AB  - Miravirsen is a beta-D-oxy-locked nucleic acid-modified phosphorothioate
      antisense oligonucleotide targeting the liver-specific microRNA-122 (miR-122).
      Miravirsen demonstrated antiviral activity against hepatitis C virus (HCV)
      genotype 1b replicons with a mean 50% effective concentration (EC50) of 0.67 MUM.
      No cytotoxicity was observed up to the highest concentration tested (>320 MUM) in
      different cell culture models, yielding a therapeutic index of >= 297.
      Combination studies of miravirsen with interferon alpha2b, ribavirin, and
      nonnucleoside (VX-222) and nucleoside (2'-methylcytidine) inhibitors of NS5B,
      NS5A (BMS-790052), or NS3 (telaprevir) indicated additive interactions.
      Miravirsen demonstrated broad antiviral activity when tested against HCV
      replicons resistant to NS3, NS5A, and NS5B inhibitors with less than 2-fold
      reductions in susceptibility. In serial passage studies, an A4C nucleotide change
      was observed in the HCV 5' untranslated region (UTR) from cells passaged in the
      presence of up to 20 MUM (40-fold the miravirsen EC50 concentration) at day 72 of
      passage but not at earlier time points (up to 39 days of passage). Likewise, a
      C3U nucleotide change was observed in the HCV 5'UTR from subjects with viral
      rebound after the completion of therapy in a miravirsen phase 2 clinical trial.
      An HCV variant constructed to contain the A4C change was fully susceptible to
      miravirsen. A C3U HCV variant demonstrated overall reductions in susceptibility
      to miravirsen but was fully susceptible to all other anti-HCV agents tested. In
      summary, miravirsen has demonstrated broad antiviral activity and a relatively
      high genetic barrier to resistance. The identification of nucleotide changes
      associated with miravirsen resistance should help further elucidate the biology
      of miR-122 interactions with HCV. (The clinical trial study has been registered
      at ClinicalTrials.gov under registration no. NCT01200420).

PMID- 25385104
TI  - Lycopene attenuates colistin-induced nephrotoxicity in mice via activation of the
      Nrf2/HO-1 pathway.
AB  - Nephrotoxicity is the major dose-limiting factor for the clinical use of colistin
      against multidrug-resistant (MDR) Gram-negative bacteria. This study aimed to
      investigate the protective effect of lycopene on colistin-induced nephrotoxicity
      in a mouse model. Fifty mice were randomly divided into 5 groups: the control
      group (saline solution), the lycopene group (20 mg/kg of body weight/day
      administered orally), the colistin group (15 mg/kg/day administered
      intravenously), the colistin (15 mg/kg/day) plus lycopene (5 mg/kg/day) group,
      and the colistin (15 mg/kg/day) plus lycopene (20 mg/kg/day) group; all mice were
      treated for 7 days. At 12 h after the last dose, blood was collected for
      measurements of blood urea nitrogen (BUN) and serum creatinine levels. The kidney
      tissue samples were obtained for examination of biomarkers of oxidative stress
      and apoptosis, histopathological assessment, and quantitative reverse
      transcription-PCR (qRT-PCR) analysis. Colistin treatment significantly increased
      concentrations of BUN and serum creatinine, tubular apoptosis/necrosis, lipid
      peroxidation, and heme oxygenase 1 (HO-1) activity, while the treatment decreased
      the levels of endogenous antioxidant biomarkers glutathione (GSH), catalase
      (CAT), and superoxide dismutase (SOD). Notably, the changes in the levels of all
      biomarkers were attenuated in the kidneys of mice treated with colistin by
      lycopene (5 or 20 mg/kg). Lycopene treatment, especially in the colistin plus
      lycopene (20 mg/kg) group, significantly downregulated the expression of NF
      kappaB mRNA (P < 0.01) but upregulated the expression of nuclear factor erythroid
      2-related factor 2 (Nrf2) and HO-1 mRNA (both P < 0.01) in the kidney compared
      with the results seen with the colistin group. Our data demonstrated that
      coadministration of 20 mg/kg/day lycopene can protect against colistin-induced
      nephrotoxicity in mice. This effect may be attributed to the antioxidative
      property of lycopene and its ability to activate the Nrf2/HO-1 pathway. 

PMID- 25385105
TI  - Carbapenem-resistant Klebsiella pneumoniae urinary tract infection following
      solid organ transplantation.
AB  - Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging pathogen with a
      devastating impact on organ transplant recipients (OTRs). Data describing urinary
      tract infections (UTIs) due to CRKP, compared to extended-spectrum beta-lactamase
      (ESBL)-producing and susceptible K. pneumoniae, are lacking. We conducted a
      retrospective cohort study comparing OTRs with a first episode of UTI due to
      CRKP, ESBL-producing K. pneumoniae, or susceptible K. pneumoniae. We identified
      108 individuals; 22 (20%) had UTIs due to CRKP, 22 (20%) due to ESBL-producing K.
      pneumoniae, and 64 (60%) due to susceptible K. pneumoniae. Compared to
      susceptible K. pneumoniae (27%), patients with UTIs due to CRKP or ESBL-producing
      K. pneumoniae were more likely to have a >= 24-hour stay in the intensive care
      unit (ICU) before or after development of the UTI (64% and 77%, respectively; P <
      0.001). Among 105/108 hospitalized patients (97%), the median lengths of stay
      prior to UTI with CRKP or ESBL-producing K. pneumoniae (7 and 8 days,
      respectively) were significantly longer than that for susceptible K. pneumoniae
      (1 day; P < 0.001). Clinical failure was observed for 8 patients (36%) with CRKP,
      4 (18%) with ESBL-producing K. pneumoniae, and 9 (14%) with susceptible K.
      pneumoniae (P = 0.073). Microbiological failure was seen for 10 patients (45%)
      with CRKP, compared with 2 (9%) with ESBL-producing K. pneumoniae and 2 (3%) with
      susceptible K. pneumoniae (P < 0.001). In multivariable logistic regression
      analyses, CRKP was associated with greater odds of microbiological failure
      (versus ESBL-producing K. pneumoniae: odds ratio [OR], 9.36, 95% confidence
      interval [CI], 1.94 to 72.1; versus susceptible K. pneumoniae: OR, 31.4, 95% CI,
      5.91 to 264). In conclusion, CRKP is associated with ICU admission, long length
      of stay, and microbiological failure among OTRs with UTIs. Greater numbers are
      needed to determine risk factors for infection and differences in meaningful
      endpoints associated with carbapenem resistance.

PMID- 25385106
TI  - Clostridium difficile isolates with high linezolid MICs harbor the
      multiresistance gene cfr.
AB  - We studied the molecular mechanisms of linezolid resistance in 9 isolates of
      toxigenic Clostridium difficile with high linezolid MICs. The activity of
      linezolid was determined against 891 clinical isolates of toxigenic C. difficile.
      The MIC50 and MIC90 of linezolid were 0.75 MUg/ml and 1.5 MUg/ml, respectively.
      Nine strains (1%) showed high linezolid MICs (6 MUg/ml to 16 MUg/ml) and also
      were resistant to clindamycin, erythromycin, and chloramphenicol. These strains
      were selected for molecular studies: sequencing of domain V of the 23 rRNA gene,
      detection of the cfr methyltransferase gene, and sequencing of the ribosomal
      protein genes rplC and rplD. Molecular relatedness between strains was assessed
      using PCR ribotyping and MLVA (multilocus variable-number tandem-repeat analysis)
      typing. The strains belonged to ribotypes 001 (2/9), 017 (6/9), and 078 (1/9).
      MLVA showed that strains of ribotype 001 and 017 belonged to the same clonal
      complex in each ribotype. We did not detect mutations in the 23S rRNA gene. The
      cfr gene was detected in 7 of 9 strains. Sequencing of cfr amplicons revealed a
      similarity of 100% to a fragment of transposon Tn6218 of C. difficile, which was
      annotated as a putative chloramphenicol/florfenicol resistance protein. We were
      unable to detect mechanisms of resistance to linezolid in the 2 strains belonging
      to ribotype 001. While the relevance of our results lies in the detection of the
      cfr gene as a possible mechanism of resistance to linezolid in C. difficile, our
      findings should be assessed by further investigations to characterize these
      possible cfr genes and their contribution to linezolid resistance. 

PMID- 25385107
TI  - Lead clinical and preclinical antimalarial drugs can significantly reduce
      sporozoite transmission to vertebrate populations.
AB  - To achieve malarial elimination, we must employ interventions that reduce the
      exposure of human populations to infectious mosquitoes. To this end, numerous
      antimalarial drugs are under assessment in a variety of transmission-blocking
      assays which fail to measure the single crucial criteria of a successful
      intervention, namely impact on case incidence within a vertebrate population
      (reduction in reproductive number/effect size). Consequently, any reduction in
      new infections due to drug treatment (and how this may be influenced by differing
      transmission settings) is not currently examined, limiting the translation of any
      findings. We describe the use of a laboratory population model to assess how
      individual antimalarial drugs can impact the number of secondary Plasmodium
      berghei infections over a cycle of transmission. We examine the impact of
      multiple clinical and preclinical drugs on both insect and vertebrate populations
      at multiple transmission settings. Both primaquine (>6 mg/kg of body weight) and
      NITD609 (8.1 mg/kg) have significant impacts across multiple transmission
      settings, but artemether and lumefantrine (57 and 11.8 mg/kg), OZ439 (6.5 mg/kg),
      and primaquine (<1.25 mg/kg) demonstrated potent efficacy only at lower
      transmission settings. While directly demonstrating the impact of antimalarial
      drug treatment on vertebrate populations, we additionally calculate effect size
      for each treatment, allowing for head-to-head comparison of the potential impact
      of individual drugs within epidemiologically relevant settings, supporting their
      usage within elimination campaigns. 

PMID- 25385108
TI  - Trends in serotype distribution and antimicrobial susceptibility in Salmonella
      enterica isolates from humans in Belgium, 2009 to 2013.
AB  - The Belgian National Reference Centre for Salmonella received 16,544 human
      isolates of Salmonella enterica between January 2009 and December 2013. Although
      377 different serotypes were identified, the landscape is dominated by S.
      enterica serovars Typhimurium (55%) and Enteritidis (19%) in a ratio which is
      inverse to European Union averages. With outbreaks of Salmonella serotypes Ohio,
      Stanley, and Paratyphi B variant Java as prime examples, 20 serotypes displayed
      significant fluctuations in this 5-year period. Typhoid strains account for 1.2%
      of Belgian salmonellosis cases. Large-scale antibiotic susceptibility analyses (n
      = 4,561; panel of 12 antibiotics) showed declining resistance levels in S.
      Enteritis and Typhimurium isolates for 8 and 3 tested agents, respectively.
      Despite low overall resistance to ciprofloxacin (4.4%) and cefotaxime (1.6%), we
      identified clonal lineages of Salmonella serotypes Kentucky and Infantis
      displaying rising resistance against these clinically important drugs. Quinolone
      resistance is mainly mediated by serotype-specific mutations in GyrA residues
      Ser83 and Asp87 (92.2% not wild type), while an additional ParC_Ser80Ile mutation
      leads to ciprofloxacin resistance in 95.5% S. Kentucky isolates, which exceeds
      European averages. Plasmid-mediated quinolone resistance (PMQR) alleles qnrA1 (n
      = 1), qnrS (n = 9), qnrD1 (n = 4), and qnrB (n = 4) were found in only 3.0% of
      533 isolates resistant to nalidixic acid. In cefotaxime-resistant isolates, we
      identified a broad range of Ambler class A and C beta-lactamase genes (e.g.,
      bla(SHV-12), blaTEM-52, bla(CTX-M-14), and bla(CTX-M-15)) commonly associated
      with members of the family Enterobacteriaceae. In conclusion, resistance to
      fluoroquinolones and cefotaxime remains rare in human S. enterica, but clonal
      resistant serotypes arise, and continued (inter)national surveillance is
      mandatory to understand the origin and routes of dissemination thereof.

PMID- 25385109
TI  - Reduced polymorphism in the Kelch propeller domain in Plasmodium vivax isolates
      from Cambodia.
AB  - Polymorphism in the ortholog gene of the Plasmodium falciparum K13 gene was
      investigated in Plasmodium vivax isolates collected in Cambodia. All of them were
      Sal-1 wild-type alleles except two (2/284, 0.7%), and P. vivax K12 polymorphism
      was reduced compared to that of the P. falciparum K13 gene. Both mutant allele
      isolates had the same nonsynonymous mutation at codon 552 (V552I) and were from
      Ratanak Kiri province. These preliminary data should encourage additional studies
      for associating artemisinin or chloroquine resistance and K12 polymorphism. 

PMID- 25385110
TI  - In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside
      reverse transcriptase inhibitor with distinct mutation development pathways.
AB  - Doravirine (DOR, formerly known as MK-1439) is a human immunodeficiency type 1
      virus (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) that is
      currently in phase 2b clinical trials. In vitro resistance selection of subtype B
      virus (MT4-green fluorescent protein [GFP] cells), as well as subtype A and C
      viruses (MT4-GFP/CCR5 cells) was conducted with DOR, rilpivirine (RPV), and
      efavirine (EFV) under low-multiplicity-of-infection conditions in a 96-well
      format. Resistance selection was performed with escalating concentrations of the
      NNRTIs ranging from the 95% effective concentration (1 * EC(95)) to 1,000 *
      EC(95) in the presence of 10% fetal bovine serum. In the resistance selection of
      subtype B virus with DOR, a V106A mutant virus led to two mutation pathways,
      followed by the emergence separately of either F227L or L234I. In the resistance
      selection of subtype A and C viruses, similar mutation development pathways were
      detected, in which a V106A or V106M mutant was also the starting virus in the
      pathways. Mutations that are commonly associated with RPV and EFV in clinical
      settings were also identified in subtype B viruses such as the E138K and K103N
      mutants, respectively, in this in vitro resistance selection study. The
      susceptibility of subtype B mutant viruses selected by DOR, RPV, and EFV to
      NNRTIs was evaluated. Results suggest that mutant viruses selected by DOR are
      susceptible to RPV and EFV and mutants selected by RPV and EFV are susceptible to
      DOR. When the replication capacity of the V106A mutant was compared with that of
      the wild-type (WT) virus, the mutant virus was 4-fold less fit than the WT virus.

PMID- 25385111
TI  - Population pharmacokinetics of gentamicin and dosing optimization for infants.
AB  - The aim of this study was to characterize and validate the population
      pharmacokinetics of gentamicin in infants and to determine the influences of
      clinically relevant covariates to explain the inter- and intraindividual
      variabilities associated with this drug. Infants receiving intravenous gentamicin
      and with routine therapeutic drug monitoring were consecutively enrolled in the
      study. Plasma concentration and time data were retrospectively collected from 208
      infants (1 to 24 months old) of the Hospital Universitario Severo Ochoa (Spain),
      of whom 44% were males (mean age [+/- standard deviation], 5.8 +/- 4.8 months;
      mean body weight, 6.4 +/- 2.2 kg). Data analysis was performed with NONMEM 7.2.
      One- and two-compartment open models were analyzed to estimate the gentamicin
      population parameters and the influences of several covariates. External
      validation was carried out in another population of 55 infants. The behavior of
      gentamicin in infants exhibits two-compartment pharmacokinetics, with total body
      weight being the covariate that mainly influences central volume (Vc) and
      clearance (CL); this parameter was also related to creatinine clearance. Both
      parameters are age related and different from those reported for neonatal
      populations. On the basis of clinical presentation and diagnosis, a once-daily
      dosage regimen of 7 mg/kg of body weight every 24 h is proposed for intravenous
      gentamicin, followed by therapeutic drug monitoring in order to avoid toxicity
      and ensure efficacy with minimal blood sampling. Gentamicin pharmacokinetics and
      disposition were accurately characterized in this pediatric population (infants),
      with the parameters obtained being different from those reported for neonates and
      children. These differences should be considered in the dosing and therapeutic
      monitoring of this antibiotic. 

PMID- 25385112
TI  - In vitro antibacterial activity of AZD0914, a new spiropyrimidinetrione DNA
      gyrase/topoisomerase inhibitor with potent activity against Gram-positive,
      fastidious Gram-Negative, and atypical bacteria.
AB  - AZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase
      inhibitor with potent in vitro antibacterial activity against key Gram-positive
      (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae,
      Streptococcus pyogenes, and Streptococcus agalactiae), fastidious Gram-negative
      (Haemophilus influenzae and Neisseria gonorrhoeae), atypical (Legionella
      pneumophila), and anaerobic (Clostridium difficile) bacterial species, including
      isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition
      of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism
      of inhibition differs from those of other marketed antibacterial compounds.
      AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double
      strand broken DNA under permissive conditions and thus blocks religation of the
      double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is
      similar to that seen with fluoroquinolones, it is mechanistically distinct.
      AZD0914 exhibited low frequencies of spontaneous resistance in S. aureus, and if
      mutants were obtained, the mutations mapped to gyrB. Additionally, no cross
      resistance was observed for AZD0914 against recent bacterial clinical isolates
      demonstrating resistance to fluoroquinolones or other drug classes, including
      macrolides, beta-lactams, glycopeptides, and oxazolidinones. AZD0914 was
      bactericidal in both minimum bactericidal concentration and in vitro time-kill
      studies. In in vitro checkerboard/synergy testing with 17 comparator
      antibacterials, only additivity/indifference was observed. The potent in vitro
      antibacterial activity (including activity against fluoroquinolone-resistant
      isolates), low frequency of resistance, lack of cross-resistance, and
      bactericidal activity of AZD0914 support its continued development. 

PMID- 25385113
TI  - Pharmacodynamic evaluation of the activities of six parenteral vancomycin
      products available in the United States.
AB  - A recent report found that generic parenteral vancomycin products may not have in
      vivo efficacies equivalent to those of the innovator in a neutropenic murine
      thigh infection model despite having similar in vitro microbiological activities
      and murine serum pharmacokinetics. We compared the in vitro and in vivo
      activities of six of the parenteral vancomycin products available in the United
      States. The in vitro assessments for the potencies of the vancomycin products
      included MIC/minimal bactericidal concentration (MBC) determinations, quantifying
      the impact of human and murine serum on the MIC values, and time-kill studies.
      Also, the potencies of the vancomycin products were quantified with a biological
      assay, and the human and mouse serum protein binding rates for the vancomycin
      products were measured. The in vivo studies included dose-ranging experiments
      with the 6 vancomycin products for three isolates of Staphylococcus aureus in a
      neutropenic mouse thigh infection model. The pharmacokinetics of the vancomycin
      products were assessed in infected mice by population pharmacokinetic modeling.
      No differences were seen across the vancomycin products with regard to any in
      vitro evaluation. Inhibitory sigmoid maximal bacterial kill (Emax) modeling of
      the relationship between vancomycin dosage and the killing of the bacteria in
      mice in vivo yielded similar Emax and EC50 (drug exposure driving one-half Emax)
      values for bacterial killing. Further, there were no differences in the
      pharmacokinetic clearances of the 6 vancomycin products from infected mice. There
      were no important pharmacodynamic differences in the in vitro or in vivo
      activities among the six vancomycin products evaluated. 

PMID- 25385114
TI  - Mechanism of beta-lactam action in Streptococcus pneumoniae: the piperacillin
      paradox.
AB  - The human pathogen Streptococcus pneumoniae has been treated for decades with
      beta-lactam antibiotics. Its resistance is now widespread, mediated by the
      expression of mosaic variants of the target enzymes, the penicillin-binding
      proteins (PBPs). Understanding the mode of action of beta-lactams, not only in
      molecular detail but also in their physiological consequences, will be crucial to
      improving these drugs and any counterresistances. In this work, we investigate
      the piperacillin paradox, by which this beta-lactam selects primarily variants of
      PBP2b, whereas its most reactive target is PBP2x. These PBPs are both essential
      monofunctional transpeptidases involved in peptidoglycan assembly. PBP2x
      participates in septal synthesis, while PBP2b functions in peripheral elongation.
      The formation of the "lemon"-shaped cells induced by piperacillin treatment is
      consistent with the inhibition of PBP2x. Following the examination of treated and
      untreated cells by electron microscopy, the localization of the PBPs by
      epifluorescence microscopy, and the determination of the inhibition time course
      of the different PBPs, we propose a model of peptidoglycan assembly that accounts
      for the piperacillin paradox. 

PMID- 25385115
TI  - Pharmacokinetics, microbial response, and pulmonary outcomes of multidose
      intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory
      colonization.
AB  - The study objectives were to refine the population pharmacokinetics (PK) model,
      determine microbial clearance, and assess short-term pulmonary outcomes of
      multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma
      respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive)
      received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3
      doses. Azithromycin concentrations were determined in plasma samples obtained up
      to 168 h post-first dose by using a validated liquid chromatography-tandem mass
      spectrometry method. Respiratory samples were obtained predose and at three time
      points post-last dose for Ureaplasma culture, PCR, antibiotic susceptibility
      testing, and cytokine concentration determinations. Pharmacokinetic data from
      these 15 subjects as well as 25 additional subjects (who received either a single
      10-mg/kg dose [n = 12] or a single 20-mg/kg dose [n = 13]) were analyzed by using
      a nonlinear mixed-effect population modeling (NONMEM) approach. Pulmonary
      outcomes were assessed at 36 weeks post-menstrual age and 6 months adjusted age.
      A 2-compartment model with all PK parameters allometrically scaled on body weight
      best described the azithromycin pharmacokinetics in preterm neonates. The
      population pharmacokinetics parameter estimates for clearance, central volume of
      distribution, intercompartmental clearance, and peripheral volume of distribution
      were 0.15 liters/h . kg(0.75), 1.88 liters . kg, 1.79 liters/h . kg(0.75), and 13
      liters . kg, respectively. The estimated area under the concentration-time curve
      over 24 h (AUC24)/MIC90 value was ~ 4 h. All posttreatment cultures were
      negative, and there were no drug-related adverse events. One Ureaplasma-positive
      infant died at 4 months of age, but no survivors were hospitalized for
      respiratory etiologies during the first 6 months (adjusted age). Thus, a 3-day
      course of 20 mg/kg/day intravenous azithromycin shows preliminary efficacy in
      eradicating Ureaplasma spp. from the preterm respiratory tract.

PMID- 25385116
TI  - Induction of Candida albicans drug resistance genes by hybrid zinc cluster
      transcription factors.
AB  - The pathogenic yeast Candida albicans can develop resistance to azole antifungal
      drugs by overexpressing ERG11, which encodes the drug target, or the multidrug
      efflux pumps MDR1 and CDR1/CDR2. The constitutive upregulation of these genes is
      usually caused by gain-of-function mutations in the zinc cluster transcription
      factors Upc2, Mrr1, and Tac1, respectively. These transcription factors are also
      required for the induction of their target genes in drug-susceptible strains in
      the presence of specific stimuli. By swapping the DNA-binding domains of Mrr1,
      Tac1, and Upc2 we investigated if the hybrid transcription factors could activate
      their new target genes in response to the same signals. When Tac1 was targeted to
      the MDR1 and ERG11 promoters, the expression of these genes became inducible by
      fluphenazine. Similarly, MDR1 and CDR2 were strongly upregulated by fluconazole
      when Upc2 was fused to the DNA-binding domains of Mrr1 and Tac1, respectively. In
      contrast, Mrr1 was unable to promote gene expression in response to benomyl when
      it was targeted to the CDR2 and ERG11 promoters instead of the MDR1 promoter.
      These results suggest that Tac1 and Upc2 themselves are activated by the inducers
      fluphenazine and fluconazole, respectively, whereas benomyl does not activate
      Mrr1 itself but a coregulatory factor that is present at the promoters of Mrr1
      target genes. Strains in which the expression levels of Mrr1 and Tac1 target
      genes were controlled by Upc2 exhibited increased fluconazole resistance,
      demonstrating that the ability to efficiently upregulate the expression of efflux
      pumps in the presence of the drug results in enhanced intrinsic fluconazole
      resistance. 

PMID- 25385117
TI  - Genomic and transcriptomic analyses of colistin-resistant clinical isolates of
      Klebsiella pneumoniae reveal multiple pathways of resistance.
AB  - The emergence of multidrug-resistant (MDR) Klebsiella pneumoniae has resulted in
      a more frequent reliance on treatment using colistin. However, resistance to
      colistin (Col(r)) is increasingly reported from clinical settings. The genetic
      mechanisms that lead to Col(r) in K. pneumoniae are not fully characterized.
      Using a combination of genome sequencing and transcriptional profiling by RNA
      sequencing (RNA-Seq) analysis, distinct genetic mechanisms were found among nine
      Col(r) clinical isolates. Col(r) was related to mutations in three different
      genes in K. pneumoniae strains, with distinct impacts on gene expression.
      Upregulation of the pmrH operon encoding 4-amino-4-deoxy-L-arabinose (Ara4N)
      modification of lipid A was found in all Col(r) strains. Alteration of the mgrB
      gene was observed in six strains. One strain had a mutation in phoQ. Common among
      these seven strains was elevated expression of phoPQ and unaltered expression of
      pmrCAB, which is involved in phosphoethanolamine addition to lipopolysaccharide
      (LPS). In two strains, separate mutations were found in a previously
      uncharacterized histidine kinase gene that is part of a two-component regulatory
      system (TCRS) now designated crrAB. In these strains, expression of pmrCAB,
      crrAB, and an adjacent glycosyltransferase gene, but not that of phoPQ, was
      elevated. Complementation with the wild-type allele restored colistin
      susceptibility in both strains. The crrAB genes are present in most K. pneumoniae
      genomes, but not in Escherichia coli. Additional upregulated genes in all strains
      include those involved in cation transport and maintenance of membrane integrity.
      Because the crrAB genes are present in only some strains, Col(r) mechanisms may
      be dependent on the genetic background.

PMID- 25385118
TI  - Testing tuberculosis drug efficacy in a zebrafish high-throughput translational
      medicine screen.
AB  - The translational value of zebrafish high-throughput screens can be improved when
      more knowledge is available on uptake characteristics of potential drugs. We
      investigated reference antibiotics and 15 preclinical compounds in a
      translational zebrafish-rodent screening system for tuberculosis. As a major
      advance, we have developed a new tool for testing drug uptake in the zebrafish
      model. This is important, because despite the many applications of assessing drug
      efficacy in zebrafish research, the current methods for measuring uptake using
      mass spectrometry do not take into account the possible adherence of drugs to the
      larval surface. Our approach combines nanoliter sampling from the yolk using a
      microneedle, followed by mass spectrometric analysis. To date, no single
      physicochemical property has been identified to accurately predict compound
      uptake; our method offers a great possibility to monitor how any novel compound
      behaves within the system. We have correlated the uptake data with high
      throughput drug-screening data from Mycobacterium marinum-infected zebrafish
      larvae. As a result, we present an improved zebrafish larva drug-screening
      platform which offers new insights into drug efficacy and identifies potential
      false negatives and drugs that are effective in zebrafish and rodents. We
      demonstrate that this improved zebrafish drug-screening platform can complement
      conventional models of in vivo Mycobacterium tuberculosis-infected rodent assays.
      The detailed comparison of two vertebrate systems, fish and rodent, may give more
      predictive value for efficacy of drugs in humans. 

PMID- 25385119
TI  - Disparities in capreomycin resistance levels associated with the rrs A1401G
      mutation in clinical isolates of Mycobacterium tuberculosis.
AB  - As the prevalence of multidrug-resistant and extensively drug-resistant
      tuberculosis strains continues to rise, so does the need to develop accurate and
      rapid molecular tests to complement time-consuming growth-based drug
      susceptibility testing. Performance of molecular methods relies on the
      association of specific mutations with phenotypic drug resistance and while
      considerable progress has been made for resistance detection of first-line
      antituberculosis drugs, rapid detection of resistance for second-line drugs lags
      behind. The rrs A1401G allele is considered a strong predictor of cross
      resistance between the three second-line injectable drugs, capreomycin (CAP),
      kanamycin, and amikacin. However, discordance is often observed between the rrs
      A1401G mutation and CAP resistance, with up to 40% of rrs A1401G mutants being
      classified as CAP susceptible. We measured the MICs to CAP in 53 clinical
      isolates harboring the rrs A1401G mutation and found that the CAP MICs ranged
      from 8 MUg/ml to 40 MUg/ml. These results were drastically different from
      engineered A1401G mutants generated in isogenic Mycobacterium tuberculosis, which
      exclusively exhibited high-level CAP MICs of 40 MUg/ml. These data support the
      results of prior studies, which suggest that the critical concentration of CAP
      (10 MUg/ml) used to determine resistance by indirect agar proportion may be too
      high to detect all CAP-resistant strains and suggest that a larger percentage of
      resistant isolates could be identified by lowering the critical concentration.
      These data also suggest that differences in resistance levels among clinical
      isolates are possibly due to second site or compensatory mutations located
      elsewhere in the genome. 

PMID- 25385120
TI  - High jugular bulb in a cohort of patients with definite Meniere's disease.

PMID- 25385121
TI  - The shrew tamed by Wolff's law: do functional constraints shape the skull through
      muscle and bone covariation?
AB  - Bone is a highly plastic tissue that reflects the many potential sources of
      variation in shape. Here, we focus on the functional aspects of bone remodeling.
      We choose the skull for our analyses because it is a highly integrated system
      that plays a fundamental role in feeding and is thus, likely under strong natural
      selection. Its principal mechanical components are the bones and muscles that
      jointly produce bite force and jaw motion. Understanding the covariations among
      these three components is of interest to understand the processes driving the
      evolution of the feeding apparatus. In this study, we quantitatively and
      qualitatively compare interactions between these three components in shrews from
      populations known to differ in shape and bite force. Bite force was measured in
      the field using a force transducer and skull shape was quantified using surface
      geometric morphometric approaches based on uCT-scans of the skulls of same
      individuals. The masseter, temporalis, pterygoideus, and digastricus muscles of
      these individuals were dissected and their cross sectional areas determined. Our
      results show strong correlations between bite force and muscle cross sectional
      areas as well as between bite force and skull shape. Moreover, bite force
      explains an important amount of skull shape variation. We conclude that
      interactions between bone shape and muscle characteristics can produce different
      morpho-functional patterns that may differ between populations and may provide a
      suitable target for selection to act upon.

PMID- 25385122
TI  - Effect of TGF-beta1 polymorphism on the susceptibility to schizophrenia and
      treatment response to atypical antipsychotic agent.
AB  - Lee H-Y, Kim Y-K. Effect of TGF-beta1 polymorphism on the susceptibility to
      schizophrenia and treatment response to atypical antipsychotic agent. OBJECTIVE:
      Several studies have suggested that cytokine alterations could be related to the
      pathophysiology of schizophrenia. Transforming growth factor-beta1 (TGF-beta1) is
      believed to be an important factor in regulation of inflammatory responses and to
      have anti-inflammatory effects. TGF-beta1 also has trophic effects on
      dopaminergic neurons. We tested the hypothesis TGF-beta1 is associated with the
      pathophysiology of schizophrenia. METHODS: The polymorphisms at codon 10 (T869C)
      and codon 25 (G915C) of TGF-beta1 were analysed in 99 schizophrenia patients and
      130 normal controls. At baseline and after 8 weeks of treatment, clinical
      symptoms were evaluated on Positive and Negative Syndrome Scale (PANSS). RESULTS:
      None of the subjects were polymorphic at codon 25. However, the C allele at codon
      10 was more frequent in schizophrenia (p = 0.05). Although schizophrenia group
      showed a higher tendency of allele frequency in the subjects with C allele (p =
      0.05), the allelic difference did not reach statistical significance after
      correction for multiple comparisons (p = 0.1). PANSS scores showed no significant
      correlation with genotypes. The genotype distribution was not significantly
      different between responders and non-responders. However, the C allele was more
      frequent among responders (p = 0.03). CONCLUSION: These results suggest that the
      TGF-beta1 polymorphism is associated with therapeutic response to antipsychotics.
      However, further studies with larger numbers of subjects are needed to confirm
      the effect of TGF-beta1 in schizophrenia.

PMID- 25385123
TI  - Anosognosia for memory impairment in Alzheimer's disease.
AB  - Stewart G, McGeown WJ, Shanks MF, Venneri A. Anosognosia for memory impairment in
      Alzheimer's disease. Objective To investigate whether patients with Alzheimer's
      disease (AD) were able to alter their awareness of memory deficits after exposure
      to a memory task. METHODS: Thirty normal older adults and 23 mild AD patients
      participated in the study. Anosognosia was assessed using discrepancies between
      self- and informant-evaluations of cognitive and functional performance.
      Participants estimated their performance on the Verbal Paired Associates task at
      different points in time (before, immediately after the task and after a 1-h
      delay). RESULTS: AD patients were generally less able to judge their memory
      abilities than healthy older adults, and tended to overestimate their task
      performance beforehand. Their prediction accuracy increased immediately after the
      task, but after a 1-h delay, they again misjudged their abilities at pretesting
      accuracy levels. Self-carer discrepancy scores of awareness of deficits in memory
      and other areas correlated significantly with memory tests but not with other
      neuropsychological tasks in the assessment, and larger discrepancy scores were
      associated with poorer performance. CONCLUSION: AD patients can monitor their
      task performance online, but are unable to maintain awareness of their deficits
      over time. Loss of awareness of memory deficits (or of any other deficits) in
      early stage AD may indicate damage to a system which updates a personal knowledge
      base with recent information. Failure to retain this information impedes
      abstraction from episodic to semantic memory.

PMID- 25385124
TI  - An adult female patient with ring chromosome 21: behavioural phenotype and
      results of high-resolution molecular characterisation.
AB  - Verhoeven WMA, Bon BV, Egger JIM, Hoischen A, Doelman JC. An adult female patient
      with ring chromosome 21: behavioural phenotype and results of high-resolution
      molecular characterisation. OBJECTIVE: A female adult patient with mild to
      moderate mental retardation and minor dysmorphisms was referred for
      neuropsychiatric examination because of psychotic and autistic symptoms and
      impulsive behaviours. METHODS: Standardized neuropsychiatric and
      neuropsychological assessment as well as detailed somatic and neurological
      examination was performed. For genetic analysis, karyotyping, whole genome array
      analysis, and high-resolution detailed analysis of chromosome 21 were carried
      through. RESULTS: Karyotyping showed a de novo ring chromosome 21:
      46,XX,der(21)r(21)(p11q22.3). High-resolution array analysis demonstrated a
      complex aberration consisting of an interstitial duplication in 21q21.1, an
      interstitial deletion in 21q22.2q22.3, an interstitial deletion in 21q22.3 and a
      terminal deletion of 21q22.3. Apart from mild dysmorphisms, visual and auditory
      impairments, and infertility, no somatic or neurological abnormalities were
      found. A formal psychiatric diagnosis could not be established. The behavioural
      problems and the supposed psychiatric symptoms could be related to her
      disharmonic social cognitive profile. The behaviour normalized after the patient
      returned to a stable and structured living environment. CONCLUSION: High
      resolution micro-array analysis techniques are essential to substantiate the
      genotype-phenotype correlation in patients with r(21) and other genetic
      disorders. Moreover, the results of this study stress the importance of the
      recognition of alexithymia as a potential cause for behavioural problems and
      psychiatric symptoms in patients with mental retardation in general.

PMID- 25385127
TI  - Disease genomics: Triaging risk variants in the non-coding genome.

PMID- 25385128
TI  - Circadian genetics: Timing is everything.

PMID- 25385131
TI  - Health care professionals' perspectives of the experiences of family caregivers
      during in-patient cancer care.
AB  - Being a family member of a patient who is being treated in an acute care setting
      for cancer often involves a number of challenges. Our study describes Norwegian
      cancer care health professionals' perceptions of family members who served as
      family caregivers (FCs) and their need for support during the in-hospital cancer
      treatment of their ill family member. Focus group discussions were conducted with
      a multidisciplinary team of 24 experienced social workers, physicians, and nurses
      who were closely involved in the patients' in-hospital cancer treatment and care.
      Drawing on qualitative hermeneutic analysis, four main themes describe health
      professionals' perceptions of FCs during the patient's in-hospital cancer care:
      an asset and additional burden, infinitely strong and struggling with
      helplessness, being an outsider in the center of care, and being in different
      temporalities. We conclude that it is a challenge for health care professionals
      to support the family and create room for FC's needs in acute cancer care. System
      changes are needed in health care, so that the patient/FC dyad is viewed as a
      unit of care in a dual process of caregiving, which would enable FCs to be given
      space and inclusion in care, with their own needs simultaneously considered
      alongside those of the patient. 

PMID- 25385132
TI  - [Metabolic surgery].

PMID- 25385129
TI  - The RNA World: molecular cooperation at the origins of life.
AB  - The RNA World concept posits that there was a period of time in primitive Earth's
      history - about 4 billion years ago - when the primary living substance was RNA
      or something chemically similar. In the past 50 years, this idea has gone from
      speculation to a prevailing idea. In this Review, we summarize the key logic
      behind the RNA World and describe some of the most important recent advances that
      have been made to support and expand this logic. We also discuss the ways in
      which molecular cooperation involving RNAs would facilitate the emergence and
      early evolution of life. The immediate future of RNA World research should be a
      very dynamic one. 

PMID- 25385133
TI  - [Patient selection as the key to success of metabolic surgery].
AB  - BACKGROUND: The indications for bariatric interventions consist of the objectives
      to improve the quality of life and to prolong survival by remission of obesity
      associated comorbidities. Until now the selection criteria for patients to
      undergo surgery which allow a prediction of therapeutic success are obscure.
      OBJECTIVE: The aim of the study was to identify the prerequisites for selection
      of overweight and obese patients to undergo bariatric surgery. RESULTS: Obesity
      per se is a proven indication for bariatric surgery due to the associated
      increase in mortality; however, not all obese patients can be considered for
      weight reduction surgery. A decisive factor for patient selection is the evidence
      of behavioral change regarding nutrition, composition and frequency of meals as
      well as increased ambulation. In patients with psychiatric diseases and
      behavioral disorders responsible for obesity a specific therapy is mandatory as
      well as intensive counseling and adherence to a lifelong follow-up. DISCUSSION:
      It seems that therapeutic success on a long-term basis is only guaranteed by
      behavioral changes. Preoperative multimodal therapy does not influence the
      outcome but it seems possible that such treatment may contribute to increased
      adherence to the behavior necessary for therapeutic success. Nevertheless, such
      treatment must not constitute a barrier against bariatric surgery. However,
      patients who are not willing to change their pathological behavior do not qualify
      for weight-reducing surgery because otherwise therapeutic success is questioned.

PMID- 25385134
TI  - [Water-filtered infrared-A (wIRA) promotes wound healing].
AB  - Water-filtered infrared-A (wIRA) is a special form of heat radiation with high
      tissue penetration and low thermal load to the skin surface which promotes the
      healing of acute and chronic wounds both by thermal and thermic as well as by non
      thermal and non-thermic effects. Water-filtered infrared-A increases tissue
      temperature (+ 2.7  degrees C at a tissue depth of 2 cm), tissue oxygen partial
      pressure (+ 32 % at a tissue depth of 2 cm) and tissue perfusion. These three
      factors are decisive for a sufficient supply of tissue with energy and oxygen and
      consequently also for wound healing and infection defense. Water-filtered
      infrared-A promotes normal as well as disturbed wound healing by diminishing
      inflammation and exudation, by promotion of infection defense and regeneration,
      and by alleviation of pain. These effects have been proven in a total of seven
      prospective studies (of these six randomized controlled studies) with most of the
      effects having an evidence level of Ia or Ib. The additional cases of complicated
      courses of wound healing presented in this article illustrate the proven effects
      of wIRA. Not only in the 6 presented cases wIRA turned the complicated courses of
      wound healing for the better and facilitated the healing of the wounds after
      varying total times of irradiation (in the 6 cases 51-550 h) and after variable
      times of wound care and mostly after transplantation of split skin grafts. In
      complicated courses of wound healing wIRA does not replace consultation and, when
      indicated, treatment by an experienced plastic surgeon and by a surgeon
      specialized in septic surgery. With these limitations wIRA can be recommended as
      a valuable complement for the treatment of acute as well as of chronic wounds.

PMID- 25385135
TI  - [Comments on: Water-filtered infrared-A (wIRA) promotes wound healing].

PMID- 25385136
TI  - [Transoral parathyroidectomy].

PMID- 25385137
TI  - [Quality of life after gastrectomy and subtotal distal resection for gastric
      carcinoma].

PMID- 25385138
TI  - [Borderline resectable pancreatic cancer: ISGPS consensus statement].

PMID- 25385139
TI  - [Sexual function disorders and micturition problems after laparoscopic and open
      rectal cancer surgery].

PMID- 25385140
TI  - [Plastic surgery coverage of pressure ulcers of the trunk and pelvic region].
AB  - Decubitus ulcers develop due to pressure on tissue resulting in decreased
      perfusion of the affected region. Areas with bony prominences are mainly
      affected. At risk are immobile patients or patients with limited mobility as well
      as people with sensitivity disorders. Patients in advanced age are more
      endangered than younger ones regarding the development of pressure ulcers and
      this patient population usually presents with a combination of extrinsic and
      intrinsic risk factors; therefore, prevention and treatment of extensive tissue
      lesions are a particular multidisciplinary challenge with high socioeconomic
      significance in respect to the demographic change with an increasing proportion
      of elderly people. Surgical treatment is of special importance for extensive
      lesions and unstable scar tissue formation. In addition to invasive wound
      cleaning by lavage, debridement and bacterial decontamination, procedures with
      local and regional tissue transfer are given priority for permanent coverage of
      skin defects. Free tissue flap techniques are also established but are less
      commonly used. Nutrition, complication management and positioning of the patient
      are mandatory additional measures for improved outcome. 

PMID- 25385141
TI  - From cellular lysis to microarray detection, an integrated thermoplastic
      elastomer (TPE) point of care Lab on a Disc.
AB  - We present an all-thermoplastic integrated sample-to-answer centrifugal
      microfluidic Lab-on-Disc system (LoD) for nucleic acid analysis. The proposed CD
      system and engineered platform were employed for analysis of Bacillus atrophaeus
      subsp. globigii spores. The complete assay comprised cellular lysis, polymerase
      chain reaction (PCR) amplification, amplicon digestion, and microarray
      hybridization on a plastic support. The fluidic robustness and operating
      efficiency of the assay were ensured through analytical optimization of
      microfluidic tools enabling beneficial implementation of capillary valves and
      accurate control of all flow timing procedures. The assay reliability was further
      improved through the development of two novel microfluidic strategies for
      reagents mixing and flow delay on the CD platform. In order to bridge the gap
      between the proof-of-concept LoD and production prototype demonstration, low-cost
      thermoplastic elastomer (TPE) was selected as the material for CD fabrication and
      assembly, allowing the use of both, high quality hot-embossing and injection
      molding processes. Additionally, the low-temperature and pressure-free assembly
      and bonding properties of TPE material offer a pertinent solution for simple and
      efficient loading and storage of reagents and other on-board components. This
      feature was demonstrated through integration and conditioning of microbeads,
      magnetic discs, dried DNA buffer reagents and spotted DNA array inserts.
      Furthermore, all microfluidic functions and plastic parts were designed according
      to the current injection mold-making knowledge for industrialization purposes.
      Therefore, the current work highlights a seamless strategy that promotes a
      feasible path for the transfer from prototype toward realistic industrialization.
      This work aims to establish the full potential for TPE-based centrifugal system
      as a mainstream microfluidic diagnostic platform for clinical diagnosis, water
      and food safety, and other molecular diagnostic applications. 

PMID- 25385143
TI  - The Immune Regulator VTCN1 Gene Polymorphisms and Its Impact on Susceptibility to
      Breast Cancer.
AB  - BACKGROUND: VTCN1, a T-cell regulator, belongs to the immunoglobulin superfamily.
      It is more highly expressed in tumor tissues than in normal tissues, which
      suggests that it could serve as a tumor-related agent. We hypothesize the gene
      variants for this coinhibitory molecule may be associated with the risk of breast
      cancer, given such gene polymorphisms could affect its related gene expression.
      METHODS: Genotypes of the VTCN1 gene variants (rs10754339, rs10801935, and
      rs3738414) were analyzed in 566 patients with breast cancer and 400 age-frequency
      matched controls. RESULTS: Compared with the major allele, the minor alleles of
      rs10754339, rs10801935, and rs3738414 did modulate the risk of breast cancer with
      ORs (95% CI) of 1.42 (1.07-1.89), 1.39 (1.10-1.77), and 0.81 (0.67-0.99),
      respectively. Those with the rs10754339 genotype AG and rs10801935 AC genotype
      had significantly increased risks when compared with their major genotypes.
      However, in rs3738414, the AA genotype had a marginally significant decreased
      risk compared with its wild genotype. In the haplotype-based analysis, the GCG
      allele was associated with significantly increased risk (OR: 1.56, 95% CI: 1.09
      2.22) based on the AAG reference. Further analyses of the haplotype pairs showed
      GCG carriers had a significantly increased risk. CONCLUSIONS: In this study, the
      VTCN1 genetic variants (rs10754339, rs10801935, and rs3738414) indicate they
      could be connected with the risk of breast cancer, which in turn provides
      indirect evidence that T-cell immunity could be involved in the development of
      breast cancer.

PMID- 25385142
TI  - Cancer drug delivery: considerations in the rational design of nanosized
      bioconjugates.
AB  - In order to efficiently deliver anticancer agents to tumors, biocompatible
      nanoparticles or bioconjugates, including antibody-drug conjugates (ADCs), have
      recently been designed, synthesized, and tested, some even in clinical trials.
      Controlled delivery can be enhanced by changing specific design characteristics
      of the bioconjugate such as its size, the nature of the payload, and the surface
      features. The delivery of macromolecular drugs to cancers largely relies on the
      leaky nature of the tumor vasculature compared with healthy vessels in normal
      organs. When administered intravenously, macromolecular bioconjugates and
      nanosized agents tend to circulate for prolonged times, unless they are small
      enough to be excreted by the kidney or stealthy enough to evade the macrophage
      phagocytic system (MPS), formerly the reticulo-endothelial system (RES).
      Therefore, macromolecular bioconjugates and nanosized agents with long
      circulation times leak preferentially into tumor tissue through permeable tumor
      vessels and are then retained in the tumor bed due to reduced lymphatic drainage.
      This process is known as the enhanced permeability and retention (EPR) effect.
      However, success of cancer drug delivery only relying on the EPR effect is still
      limited. To cure cancer patients, further improvement of drug delivery is
      required by both designing superior agents and enhancing EPR effects. In this
      Review, we describe the basis of macromolecular or nanosized bioconjugate
      delivery into cancer tissue and discuss current diagnostic methods for evaluating
      leakiness of the tumor vasculature. Then, we discuss methods to augment
      conventional "permeability and retention" effects for macromolecular or nanosized
      bioconjugates in cancer tissue. 

PMID- 25385144
TI  - Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1alpha/miR-210/Bcl
      2 pathway in colon cancer cells.
AB  - Autophagy is an evolutionarily conserved cellular response to conditions of
      stress such as hypoxia, which induce radioresistance in cancer cells. We studied
      the mechanism of action of hypoxia on autophagy and radiosensitivity in colon
      cancer cells. In the human colon cancer cell lines SW480 and SW620,
      autophagosomes were analyzed to evaluate autophagy by flow cytometry. The
      expression of hypoxia inducible factor-1alpha (HIF-1alpha), Bcl-2, and miR-210
      was detected by western blotting and quantitative real-time polymerase chain
      reaction (PCR). HIF-1alpha and miR-210 inhibition was induced by siRNA
      transfections. Apoptosis detection and colony assays were performed to determine
      radiosensitivity. HIF-1alpha and miR-210 showed a significant increase under
      hypoxic condition. The inhibition of HIF-1alpha decreased miR-210 expression and
      autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the
      survival fraction of colon cancer cells after radiation treatment. Under hypoxia,
      HIF-1alpha induces miRNA-210 which in turn enhances autophagy and reduces
      radiosensitivity by downregulating Bcl-2 expression in colon cancer cells. Our
      results imply that autophagy contributes to the reduction of radiosensitivity in
      hypoxic environment, and the process is mediated through the HIF-1alpha/miR
      210/Bcl-2 pathway in human colon cancer cells. 

PMID- 25385145
TI  - The use of research evidence on patient preferences in pharmaceutical coverage
      decisions and clinical practice guideline development: exploratory study into
      current state of play and potential barriers.
AB  - BACKGROUND: The patient perspective is increasingly considered in healthcare
      policy decisions. The use of research on patient preferences seems however
      limited. Using the available research on patient preferences would make
      healthcare policy decisions more evidence-based regarding the patient
      perspective. Objective of this study is to investigate whether and how results of
      research on patient preferences are incorporated in current procedures for
      pharmaceutical coverage decisions and clinical practice guideline (CPG)
      development. METHODS: A document analysis on procedure descriptions was combined
      with case studies. Analyses were performed for five European countries. In the
      document analysis we systematically checked whether the procedure provides
      guidance on the systematic use of research on patient preferences, and whether
      the search and use of research on patient preferences is mentioned in the
      decision making procedure. In the case studies, which were for exploratory
      purposes, we scored whether or not research question on patient preferences were
      formulated, whether or not a search strategy including terms relating to patient
      preferences was mentioned, whether results of this search strategy were shown and
      finally, how many references with preference-related terms were included in the
      reference list of the case. RESULTS: None of the procedures for pharmaceutical
      coverage decisions mentions the systematic consideration of research on patient
      preferences. For CPG development, the Scottish procedure refers to a mandatory
      literature search. In the Netherlands this step is optional. In the case studies
      for pharmaceutical coverage decisions only one reference related to patient
      preferences was found. Some of the case studies for CPG included research
      questions, search strategies and references relating to patient preferences.
      CONCLUSIONS: This study illustrates that systematic consideration of research on
      patient preferences in pharmaceutical coverage decisions and guideline
      development is limited, or if taken into account, this is not visible. This
      contrasts the strong movement towards patient involvement in health care. Several
      potential barriers may explain the limited use of research on patient
      preferences.

PMID- 25385146
TI  - Suppression of dendritic cell and T-cell activation by the pRST98 Salmonella
      plasmid.
AB  - Salmonella evades host immune response via the expression of a variety of
      pathogenic factors. The 'pRST98' plasmid of Salmonella enterica serotype Typhi
      (S. Typhi) is involved in conferring the multidrug-resistance and virulence of S.
      typhi. However, its specific effect on host-cell function has remained elusive.
      Dendritic cells (DCs) are key regulators of immune responses. The present study
      therefore aimed to investigate whether pRST98 may target DCs involved in
      mediating the adaptive immune response. In vivo experiments with Salmonella
      enterica serotype Typhimurium chi3337 and chi3337/pRST98 revealed that pRST98 may
      influence multiple important functions of murine DCs, including maturation,
      survival and cytokine production. In addition, pRST98 markedly contributed to
      decreasing T-cell activation. These data suggested that by targeting the
      aforementioned functions of DCs, pRST98 may partially overturn the adaptive
      immune defense mechanisms of the host, which are required for elimination of this
      pathogen from infected tissues. This may contribute to the evasion of host
      adaptive immune responses by S. Typhi and therefore provide a target for the
      prevention and treatment of typhoid fever.

PMID- 25385147
TI  - A novel stable binary BeB2 phase [corrected].
AB  - Potential crystal structures of BeB2 were explored using ab initio evolutionary
      simulations. A new phase with a Cmcm space group was uncovered. It was determined
      that the Cmcm phase is mechanically and dynamically stable and has a lower
      enthalpy, from ambient pressure up to 13 GPa, than any previously proposed
      phases, as measured using first-principles calculations. The crystal structure,
      phonon dispersion, phase transitions, and mechanical and electronic properties of
      this phase were investigated. It was determined that the Cmcm phase may transform
      into the phase at pressures higher than 13 GPa. The band structures and density
      of states reveal that the Cmcm phase is metallic. In addition, the Vickers
      hardness was calculated using three empirical models. To explain the origin of
      the hardness, charge density difference maps and a Mulliken population analysis
      were carried out, which demonstrated that there are strong covalent interactions
      between B atoms. By analyzing the Crystal Orbital Hamilton Population (COHP)
      diagrams, it was determined that the total interaction of the Be-B bonds is
      stronger than that of the B-B bonds, indicating a very complex bonding feature in
      the new phase. It was predicted that the new Cmcm phase is nearly absent of
      superconductivity.

PMID- 25385149
TI  - PERSPECTIVES ON MONITORING MENTAL HEALTH LEGISLATION IN ENGLAND: A VIEW FROM THE
      FRONT LINE.
AB  - This article discusses the findings of an exploratory study involving semi
      structured interviews with a sample of Mental Health Act (MHA) Commissioners. MHA
      Commissioners are employed by the Care Quality Commission (CQC) in England to
      monitor patients who are deprived of their liberty under the Mental Health Act
      1983 (as amended by the Mental Health Act 2007). The study was designed to
      examine the impact of the transfer of responsibility of mental health detention
      monitoring in April 2009 from the Mental Health Act Commission to the CQC. The
      interviews were devised around the United Nations Optional Protocol to the
      Convention Against Torture (OPCAT) framework, which provides a useful benchmark
      for effective monitoring of deprivations of liberty to national inspection bodies
      (known as National Preventive Mechanisms), such as the CQC. Article 18 of the
      OPCAT advises a regular system of preventive visits by independent expert
      monitors, as well focussing on the promotion and protection of human rights.
      There is paucity of data on the work of MHA Commissioners in England to date and
      the author was unable to locate any previous studies on the subject. This study
      is timely and important as the CQC has been heavily criticised following the
      abuses uncovered at Winterbourne View care home and in the wake of the Mid
      Staffordshire Inquiry. Consequently, in 2012, the CQC undertook a major strategic
      review. The findings of this study suggest that, whilst there is some evidence of
      compliance, the CQC still has some way to go to effectively fulfil its monitoring
      duties in line with the provisions of the OPCAT. 

PMID- 25385150
TI  - The application of functional silica nanoparticles to fulfill the rapid and
      improved enantioselective capillary electrophoresis separation of amino acid
      derivatives.
AB  - In this study, diamino moiety functionalized silica nanoparticles with the size
      of 118 +/- 12 nm were successfully synthesized and directly introduced into a
      chiral capillary electrophoresis system to improve the enantioseparation of 9
      fluorenyl methoxycarbonyl derivatized amino acids using norvancomycin as chiral
      selector. Under acidic background electrolyte conditions, functional silica
      nanoparticles can be readily adsorbed onto the inner surface of bare silica
      capillary column through electrostatic interaction to form a dynamic coating,
      resulting in a reversed anodic electro-osmotic flow (i.e. from cathode to anode).
      As expected, chiral amino acid derivatives (usually negatively charged) can be
      rapidly separated under co-electro-osmotic flow conditions in the current
      separation system. Furthermore, the column performance and detection sensitivity
      for the enantioseparation were also obviously improved because the adsorption of
      chiral selector of norvancomycin to the capillary wall was greatly suppressed.
      Some important factors influencing the separation, such as the coating thickness,
      background electrolyte concentration, functional silica nanoparticles
      concentration, and the organic modifier were also investigated and the optimized
      separation conditions were obtained. 

PMID- 25385148
TI  - Golgi phosphoprotein 3 (GOLPH3) promotes hepatocellular carcinoma cell
      aggressiveness by activating the NF-kappaB pathway.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, in which
      the NF-kappaB pathway plays an important role and is constitutively activated.
      Better understanding of the molecular pathogenesis of HCC and the NF-kappaB
      pathway are needed to improve patient outcomes. Herein, we identified an
      unappreciated protein involved in NF-kappaB-induced activation, Golgi
      phosphoprotein 3 (GOLPH3). The mRNA and protein expression levels of GOLPH3 were
      frequently up-regulated in HCC and GOLPH3 expression correlated closely with
      clinical stage and survival in both the testing and validation cohorts. Ectopic
      over-expression of GOLPH3 in PLC/PRF/5 (PLC) and Huh7 HCC cells protected against
      cisplatin-induced apoptosis, promoted angiogenesis and proliferation and
      increased the aggressiveness of HCC cells in vitro and in vivo, whereas
      inhibition of GOLPH3 led to decreased aggressiveness. Through analysis of two
      published HCC patient profiles, GOLPH3 expression significantly correlated with
      NF-kappaB signalling. Furthermore, we demonstrated that GOLPH3 promoted K63
      linked polyubiquitination of tumour necrosis factor receptor-associated factor 2
      (TRAF2), receptor interacting protein (RIP) and NF-kappaB essential modulator
      (NEMO) and substantially sustained the activation of NF-kappaB in HCC cells.
      Taken together, our findings provided evidence that GOLPH3 is a prognostic and/or
      potential therapeutic biomarker for HCC patients and plays an important role in
      activation of the NF-kappaB pathway during HCC progression.

PMID- 25385157
TI  - Clinical features of 280 hospitalized patients with lymphangioleiomyomatosis in
      Japan.
AB  - BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is rare, but potentially
      life threatening owing to respiratory failure. However, knowledge is limited
      about the condition of hospitalized LAM patients. The objectives of this study
      were to investigate patient characteristics, comorbidities and causes of death
      among hospitalized LAM patients in Japan. METHODS: Using a national inpatient
      database in Japan, information on 280 LAM patients hospitalized between July 2010
      and March 2013 was retrospectively collected. We divided the 280 patients into
      three groups according to their status regarding lung transplantation. RESULTS:
      For the study period, we identified 32 patients who had undergone lung
      transplantation ('after-transplantation' group), 12 patients admitted for lung
      transplantation ('for-transplantation') and 236 patients who had not undergone
      transplantation ('no-transplantation'). Although the clinical features of LAM
      patients in the 'no-transplantation' group were similar to previously reported
      findings, patients hospitalized in connection with transplantation showed the
      following: the activities of daily living score using the Barthel Index in the
      'after-transplantation' group (89.4) was significantly higher than in the 'for
      transplantation' group (64.6); the mortality rates in the after-transplantation
      group (3.1%) were significantly lower than in the for-transplantation group
      (25%). The most frequent comorbidity was pneumothorax, followed by respiratory
      failure and angiomyolipoma, although there was no significant difference in the
      prevalence among the three groups. CONCLUSIONS: We determined the clinical
      features, comorbidities and fatalities in hospitalized LAM patients. Patients
      with LAM after transplantation had higher activities of daily living scores than
      those before transplantation, which suggests that lung transplantation may
      improve activities of daily living.

PMID- 25385159
TI  - Cyclic trinuclear copper(I), silver(I), and gold(I) complexes: a theoretical
      insight.
AB  - The metal-ligand, M-L, bonding situation in cyclic trinuclear complexes, CTCs, of
      copper(I), silver(I), and gold(I) was investigated in terms of the energy
      decomposition analysis (EDA-NOCV) and natural bond orbitals (NBOs). The
      anisotropy of the induced current density (ACID) and magnetic response were
      employed to evaluate the effect of electronic conjugation and metal-metal
      interactions in CTCs. The EDA-NOCV results show that the M-L bonding is stronger
      in gold(I) than in copper(I) or silver(I) complexes. Au(+)-L bonds present an
      elevated covalent character when compared with Cu(+)-L and Ag(+)-L bonds. The NBO
      analysis confirms the elevated covalent character observed for Au(+)-L bonds,
      indicating that the ligand-metal donation, L -> M, and the metal-ligand back
      donation, M -> L, are more stabilizing in gold(I) than in copper(I) or silver(I)
      complexes. Both ACID and the magnetic response calculations reveal that there are
      cyclic conjugations in the ligands and a strong diatropic ring current indicating
      the presence of aromaticity. However, there is no through-bond M-L conjugation
      between the ligands and the metallic centers, as indicated by the absence of a
      continuous anisotropy boundary surface involving M-L bonds.

PMID- 25385158
TI  - A study of possible associations between single nucleotide polymorphisms in the
      estrogen receptor 2 gene and female sexual desire.
AB  - INTRODUCTION: Female sexual desire and arousal problems have been shown to have a
      heritable component of moderate size. Previous molecular genetic studies on
      sexual desire have mainly focused on genes associated with neurotransmitters such
      as dopamine and serotonin. Nevertheless, there is reason to believe that hormones
      with more specific functions concerning sexuality could have an impact on sexual
      desire and arousal. AIM: The aim of the present study was to investigate the
      possible effects of 17 single nucleotide polymorphisms (SNPs) located in estrogen
      receptor genes on female sexual desire and subjective and genital arousal
      (lubrication). Based on previous research, we hypothesized that ESR1 and ESR2 are
      relevant genes that contribute to female sexual desire and arousal. MAIN OUTCOME
      MEASURES: The desire, arousal, and lubrication subdomains of the Female Sexual
      Function Index self-report questionnaire were used. METHODS: The present study
      involved 2,448 female twins and their sisters aged 18-49 who had submitted saliva
      samples for genotyping. The participants were a subset from a large-scale,
      population-based sample. RESULTS: We found nominally significant main effects on
      sexual desire for three ESR2 -linked SNPs when controlled for anxiety, suggesting
      that individuals homozygous for the G allele of the rs1271572 SNP, and the A
      allele of the rs4986938 and rs928554 SNPs had lower levels of sexual desire. The
      rs4986938 SNP also had a nominally significant effect on lubrication. No effects
      for any of the SNPs on subjective arousal could be detected. CONCLUSIONS: The
      number of nominally significant results for SNPs in the ESR2 gene before
      correcting for multiple testing suggests that further studies on the possible
      influence of this gene on interindividual variation in female sexual functioning
      are warranted. In contrast, no support for an involvement of ESR1 was obtained.
      Our results should be interpreted with caution until replicated in independent,
      large samples.

PMID- 25385160
TI  - Congenital diseases and semaphorin signaling: overview to date of the evidence
      linking them.
AB  - Semaphorins and their receptors, neuropilins and plexins, were initially
      characterized as a modulator of axonal guidance during development, but are now
      recognized as a regulator of a wide range of developmental events including
      morphogenesis and angiogenesis, and activities of the immune system. Owing to the
      development of next-generation sequencing technologies together with other useful
      DNA assays, it has also become clear that semaphorin signaling plays a crucial
      role in many congenital diseases such as retinal degeneration and congenital
      heart defects. This review summarizes the recent knowledge about the relationship
      between a variety of congenital diseases and semaphorin signaling. 

PMID- 25385161
TI  - Synthesis of shape-controlled La2NiO(4+delta) nanostructures and their
      anisotropic properties for oxygen diffusion.
AB  - This study highlights the synthesis of shape-controlled La2NiO(4+delta)
      nanostructures using a reverse microemulsion method. We report that surfactant to
      water mass ratio plays a key role in controlling the shape of the nanostructures.
      These nanostructures show a strong dependence of their oxygen transport
      properties on their geometries.

PMID- 25385162
TI  - Equitable access to comprehensive surgical care: the potential of indigenous
      private philanthropy in low-income settings.
AB  - INTRODUCTION: Equitable access to surgical care is necessary for improving global
      health. We report on the performance, financial sustainability, and policy impact
      of a free-of-cost multispecialty surgical delivery program in Karachi, Pakistan
      built upon local private philanthropy. MATERIALS AND METHODS: We evaluated trends
      in surgical service delivery, expenditures, and philanthropic donations from
      Indus Hospital's first 5 years of operation (2007-2012), projected these over the
      hospital's current expansion phase, compared these to publicly accessible records
      of other philanthropic hospitals providing surgical care, and documented the
      government's evolving policies toward this model. RESULTS: Between 2007 and 2012,
      Indus Hospital treated 40,012 in-patients free of cost, 33,606 (84 %) of them for
      surgical procedures. Surgical procedures increased fivefold to 9,478 during 2011
      2012 from 1,838 during 2007-2008. Bed occupancy increased to 91 % from 65 % over
      the same period. External surgical missions accounted for less than 0.5 % of
      patients served. Ninety-eight percent (98 %) of all philanthropic donations-
      totaling USD 26.6 million over 2007-2012--were locally generated. Zakat
      (obligatory annual religious alms in the Islamic faith) constituted 34 % of all
      donations, followed by unrestricted funds (24 %) and donations-in-kind (24 %),
      buildings (12 %), grants (5 %), and return on investments (1 %). Overall,
      donations received between 2007 and 2012 increased sevenfold, with Zakat
      increasing 12-fold. During 2013-2014, the Government of Pakistan provided land
      lease and annual operational grants totaling USD 9 million. CONCLUSIONS: Local
      philanthropy can sustain and grow the provision of free, high-quality surgical
      care in low-income settings, and encourage the development of hybrid government
      philanthropic models of surgical care.

PMID- 25385163
TI  - Effect of lipid-modifying therapy on long-term mortality after abdominal aortic
      aneurysm repair: a systemic review and meta-analysis.
AB  - BACKGROUND: Several observational studies have demonstrated that lipid-modifying
      therapy may improve long-term survival in abdominal aortic aneurysm (AAA)
      patients after repair. We carried out a systematic review and meta-analysis of
      studies evaluating the effect of lipid-modifying therapy on long-term mortality.
      PATIENTS AND METHODS: We conducted a systematic search of multiple databases up
      to April 2014. Studies that evaluated exposure to lipid-modifying therapy,
      reported mortality data and hazard ratio (HR) or provided survival curve for
      their estimation were included in the meta-analysis. Pooled HR estimates with 95%
      confidence intervals (CIs) were calculated using the random-effects model.
      RESULTS: Eight studies (seven cohorts, one post hoc study of a randomization
      controlled trial) reporting 2,605 patients on lipid-modifying therapy were
      included. Meta-analysis showed a significant 39% reduction in long-term mortality
      with lipid-modifying therapy (HR 0.61; 95% CI 0.51-0.73). After exclusion of one
      study which was contributing to considerable heterogeneity, a significant 33%
      reduction in mortality risk was a more conservative, consistent estimate (HR
      0.67; 95% CI 0.59-0.77). CONCLUSION: Meta-analysis of studies supports a
      protective role of lipid-modifying therapy on mortality risk after AAA repair.
      Aggressive lipid intervention should be recommended to those who receiving AAA
      repair.

PMID- 25385164
TI  - The molecular mechanism of HOTAIR in tumorigenesis, metastasis, and drug
      resistance.
AB  - Long non-coding RNAs have been reported to play an important role in cellular
      metabolism and development. Homeobox transcript antisense intergenic RNA
      (HOTAIR), a long non-coding RNA, is pervasively over-expressed in most human
      cancers compared with non-cancerous adjacent tissues. Although many articles have
      reported that HOTAIR is closely associated with metastasis, epithelial
      mesenchymal transition, advanced pathological stage, drug resistance, and poor
      prognosis, the role of HOTAIR in gene regulation and tumor development is largely
      unknown, and the potential molecular mechanisms are not completely clear yet. In
      this review, we summarized the recent progress in the study of the major
      functions of HOTAIR. miR-331-3p, miR-130a, miR-7, miR-141, HER2, c-MYC, WIF-1,
      RBM38, PTEN, and Col-1 are involved in the HOTAIR regulation network. We tried to
      elucidate the molecular mechanisms of HOTAIR in the aspects of tumorigenesis,
      metastasis, drug resistance, and regulation. 

PMID- 25385165
TI  - Developing mental health mobile apps: Exploring adolescents' perspectives.
AB  - Mobile applications or 'apps' have significant potential for use in mental health
      interventions with adolescents. However, there is a lack of research exploring
      end users' needs from such technologies. The aim of this study was to explore
      adolescents' needs and concerns in relation to mental health mobile apps. Five
      focus groups were conducted with young people aged 15-16 years (N = 34, 60%
      male). Participants were asked about their views in relation to the use of mental
      health mobile technologies and were asked to give their responses to a mental
      health app prototype. Participants identified (1) safety, (2) engagement, (3)
      functionality, (4) social interaction, (5) awareness, (6) accessibility, (7)
      gender and (8) young people in control as important factors. Understanding end
      users' needs and concerns in relation to this topic will inform the future
      development of youth-oriented mental health apps that are acceptable to young
      people.

PMID- 25385166
TI  - The efficacy of a supervised and a home-based core strengthening programme in
      adults with poor core stability: a three-arm randomised controlled trial.
AB  - BACKGROUND: Poor core stability is linked to a range of musculoskeletal
      pathologies and core-strengthening programmes are widely used as treatment.
      Treatment outcomes, however, are highly variable, which may be related to the
      method of delivery of core strengthening programmes. We investigated the effect
      of identical 8 week core strengthening programmes delivered as either supervised
      or home-based on measures of core stability. METHODS: Participants with poor core
      stability were randomised into three groups: supervised (n=26), home-based (n=26)
      or control (n=26). Primary outcomes were the Sahrmann test and the Star Excursion
      Balance Test (SEBT) for dynamic core stability and three endurance tests (side
      bridge, flexor and Sorensen) for static core stability. The exercise programme
      was devised and supervised by an exercise physiologist. RESULTS: Analysis of
      covariance on the change from baseline over the 8 weeks showed that the
      supervised group performed significantly better on all core stability measures
      than both the home-based and control group. The home-based group produced
      significant improvements compared to the control group in all static core
      stability tests, but not in most of the dynamic core stability tests (Sahrmann
      test and two out of three directions of the SEBT). CONCLUSIONS: Our results
      support the use of a supervised core-strengthening programme over a home-based
      programme to maximise improvements in core stability, especially in its dynamic
      aspects. Based on our findings in healthy individuals with low core stability,
      further research is recommended on potential therapeutic benefits of supervised
      core-strengthening programmes for pathologies associated with low core stability.
      TRIAL REGISTRATION NUMBER: ACTRN12613000233729.

PMID- 25385167
TI  - Sports medicine ultrasound (US) beyond the musculoskeletal system: use in the
      abdomen, solid organs, lung, heart and eye.
AB  - The use of point-of-care ultrasound (US) by non-radiologists is not new and the
      expansion into sports medicine practice is relatively young. US has been used
      extensively to evaluate the musculoskeletal system including the diagnosis of
      muscle, tendon and bone injuries. However, as sports medicine practitioners we
      are responsible for the care of the entire athlete. There are many other non
      musculoskeletal applications of US in the evaluation and treatment of the
      athlete. This paper highlights the use of US in the athlete to diagnose
      pulmonary, cardiac, solid organ, intra-abdominal and eye injuries. 

PMID- 25385168
TI  - Incidence, mechanism and risk factors for injury in youth rock climbers.
AB  - BACKGROUND: Rock-climbing participation has grown globally in recent years, and
      the sport was officially recognised by the International Olympic Committee in
      2010. The epidemiology of climbing injuries in adults has been examined, but few
      studies have investigated injury in youth climbers. OBJECTIVE: To examine the
      incidence, mechanisms and risk factors for injury in recreational and elite sport
      climbers and boulderers aged 11-19 years. STUDY DESIGN: Cross-sectional. METHODS:
      Youth (n=116) were recruited from climbing facilities across Alberta, Canada.
      Participants completed an anonymous questionnaire from October 2012 to March
      2013. Climbing injury incidence proportions and incidence rates (IR) were
      calculated. ORs with corresponding 95% CIs were estimated for possible risk
      factors. RESULTS: The injury IR was 4.44 injuries/1000 climbing hours (95% CI
      3.74 to 5.23). Sprains (27%) and strains (26%) were the predominant injury types,
      and repetitive overuse was the primary mechanism of injury (42%). Hands and
      fingers were the most commonly injured locations (21%). Exploratory analyses
      showed three risk factors for injury: older age (15-19 vs 11-14 years; OR=11.30,
      95% CI 2.33 to 54.85), injury in a sport other than climbing (OR=6.46, 95% CI
      1.62 to 25.68) and preventive taping (OR=5.09, 95% CI 1.44 to 18.02).
      CONCLUSIONS: Injury risk is high in youth climbers. Findings are consistent with
      the reported rates, types and mechanisms in adults. Modifiable risk factors
      warrant further investigation to inform the development of injury prevention
      strategies, targeting high-risk climbers including adolescents and those with
      previous injury.

PMID- 25385169
TI  - Synchronous double cancers of primary hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma: a case report and review of the literature.
AB  - We report a case of double primary liver cancer comprising hepatocellular
      carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A 58-year-old Chinese
      man without obvious liver cirrhosis was diagnosed with multiple HCC in segment V
      (SV) and segment VIII (SVIII) of the liver. Preoperative abdominal magnetic
      resonance imaging revealed two solid masses in SV and SVIII. We performed hepatic
      resection of both segments. The tumors in SV and SVIII were pathologically
      diagnosed as HCC and ICC, respectively. Immunohistochemically, the HCC in SV was
      positive for carcinoembryonic antigen and negative for alpha-fetoprotein (AFP)
      and cytokeratin (CK), while the ICC in SVIII was negative for both AFP and CK.
      These observations confirmed the diagnosis of double primary liver cancer (HCC
      and ICC). Double primary liver cancer is extremely rare. We herein review
      previous reports of patients with a histological diagnosis of double primary
      liver cancer. Based on the findings of this case and the literature review, we
      speculate that the imaging findings of double primary hepatic cancer conform to
      the pathologic findings. 

PMID- 25385170
TI  - Celebrating Soft Matter's 10th Anniversary: toward jamming by design.
AB  - In materials science, high performance is typically associated with regularity
      and order, while disorder and the presence of defects are assumed to lead to sub
      optimal outcomes. This holds for traditional solids such as crystals as well as
      for many types of nanoscale devices. However, there are circumstances where
      disorder can be harnessed to achieve performance not possible with approaches
      based on regularity. Recent research has shown opportunities specifically for
      soft matter. There, the phenomenon of jamming leads to unique emergent behavior
      that enables disordered, amorphous systems to switch reversibly between solid
      like rigidity and fluid-like plasticity. This makes it possible to envision
      materials that can change stiffness or even shape adaptively. We review some of
      the progress in this direction, discussing examples where jamming has been
      explored from micro to macro scales in colloidal systems, suspensions, granular
      materials-enabled soft robotics, and architecture. We focus in particular on how
      the jammed aggregate state can be tailored by controlling particle level
      properties and discuss very recent ideas that provide an important first step
      toward actual design of specifically targeted jamming behavior. 

PMID- 25385171
TI  - Compensatory growth feeding strategy does not overcome negative effects on growth
      and carcass composition of low birth weight pigs.
AB  - The aim of this study was to evaluate whether the compensatory growth feeding
      strategy could be a suitable solution for overcoming the negative effects on
      growth, carcass composition and meat quality of low birth weight pigs. Forty-two
      Swiss Large White barrows from 21 litters were selected at weaning and
      categorized into either being light (L; >0.8 and <1.3 kg) or heavy (H; >1.7 kg)
      birth weight pigs. From 27.8 kg BW, pigs were assigned within birth weight group
      to one of three feeding groups: AA: ad libitum access to the grower and finisher
      diet, RR: restricted access to the grower and finisher diet or RA: restricted
      access to the grower diet and ad libitum access to the finisher diet. At
      slaughter, the longissimus (LM) and semitendinosus (STM) muscles were removed
      from the right side of the carcass. Weight, girth and length of the STM and the
      LM area were determined after muscle excision. Carcass characteristics and meat
      quality traits were assessed. Using mATPase histochemistry, myofibre size and
      myofibre type distribution were determined in the LM and STM. Because of longer
      days on feed, total feed intake was greater (P<0.01) and feed efficiency was
      lower (P<0.01) in L than H barrows. Regardless of the birth weight group, AA and
      RA barrows grew faster (P<0.05) than RR barrows. During the compensatory growth
      period, RA barrows grew faster (P<0.05) than AA or RR barrows. Growth efficiency
      did not differ between RA and RR barrows but was greater (P<0.05) compared with
      AA barrows. Carcasses of L barrows were fatter as indicated by the lower
      (P?<=0.05) lean meat and greater (P?0.02) omental and subcutaneous fat
      percentage. Lean meat percentage was lower (P?0.05) in AA and RA than RR barrows.
      These differences caused by ad libitum feed access tended to be greater (feeding
      regime * birth weight group interaction; P<0.08) in L than H barrows. In L
      barrows, slow oxidative, fast oxidative glycolytic and overall average myofibre
      size of the LM and the fast glycolytic myofibres and overall average myofibre
      size of the dark portion of the STM were larger (P?0.03) than in H barrows. The
      study revealed that the compensatory growth feeding strategy was inadequate in
      overcoming the disadvantages of low birth weight.

PMID- 25385173
TI  - Circulating Toll-like receptor 4-responsive microRNA panel in patients with
      coronary artery disease: results from prospective and randomized study of
      treatment with renin-angiotensin system blockade.
AB  - The extracellular miRNAs circulate in the bloodstream and may serve as novel
      diagnostic and therapeutic biomarkers. The aim of the present study was to
      investigate circulating Toll-like receptor 4 (TLR4)-responsive miRNA expression
      in patients with coronary artery disease (CAD) and to examine the effects of
      renin-angiotensin system (RAS) blockade and statins on miRNA levels. This study
      included 41 patients with CAD and 20 subjects without CAD (non-CAD). Plasma TLR4
      responsive miRNA samples were analysed using a microarray assay for 1700 human
      miRNA. The candidate miRNAs were verified with real-time reverse transcription
      (RT)-PCR. Patients with CAD were randomized to 12 months of combined treatment
      with either telmisartan and atorvastatin [angiotensin II receptor blocker (ARB)]
      or enalapril and atorvastatin [angiotensin-converting enzyme inhibitor (ACEI)].
      Plasma samples were obtained from peripheral blood at baseline and after 12
      months. The microarray assay showed significant differences in seven TLR4
      responsive miRNAs between the CAD and non-CAD groups (P<0.05). Real-time PCR
      verified that miR-31, miR-181a, miR-16 and miR-145 were significantly lower in
      the CAD group than in the non-CAD group (P<0.01). Levels of TLR4 protein were
      higher in the CAD group than in the non-CAD group (P<0.01) and were negatively
      correlated with levels of TLR4-responsive miRNAs. Receiver operating
      characteristic (ROC) curve analysis revealed that a panel of these four miRNAs
      was sensitive and specific enough to distinguish CAD from non-CAD [area under the
      curve (AUC)=0.93, 95% CI (confidence interval)=0.99-0.87]. Both ARB and ACEI
      groups showed increased TLR4-responsive miRNAs and diminished levels of TLR4
      protein (P<0.05). Changes in miRNAs and TLR4 levels were greater in the ARB group
      than in the ACEI group (P<0.05). Circulating TLR4-responsive miRNAs including miR
      31, miR-181a, miR-16 and miR-145 were significantly lower in patients with CAD
      compared with controls and these miRNAs may be involved in the pathogenesis of
      CAD. 

PMID- 25385174
TI  - Fragmented Red Cell as a Possible Favorable Prognostic Marker of Hematopoietic
      Stem Cell Transplantation Associated Thrombotic Microangiopathy.
AB  - BACKGROUND: Fragmented red cell (FRC) by automated hematologic analyzer is known
      to detect schistocyte. In this study, it is noted that FRC might be a favorable
      prognostic marker of hematopoietic stem cell transplantation associated
      thrombotic microangiopathy (TA-TMA). METHODS: The peripheral blood samples and
      clinical data of 89 patients were collected. The diagnosis of TA-TMA was defined
      by the Blood and Marrow Transplant Clinical Trials Network's criteria and
      schistocyte or both schistocyte- and FRC-positive cases and other parameters
      fulfilled are regarded as TA-TMA. RESULTS: Schistocyte and FRC displayed a
      correlation coefficient of 0.461 (P < 0.001) by Spearman's method. The diagnostic
      concordance of TA-TMA using schistocyte and FRC was 92.1% with kappa index of
      0.531 (P < 0.001). The number of diagnosed patients and mean survival month were
      as follows: TA-TMA by schistocyte, 8 (8.9%), 13.5 month; TA-TMA by schistocyte
      and FRC, 7 (7.8%), 40.4 month; No TMA, 74 (83.1%), 38.3 month, respectively.
      Kaplan-Meier survival analysis by log-rank method of the patient with TA-TMA by
      schistocyte and rest of the group showed statistical significance (P < 0.01).
      CONCLUSION: As evidenced by the data, FRC might be a favorable prognostic marker
      for TA-TMA, but additional studies with larger patients groups are required for
      validation of clinical applications.

PMID- 25385175
TI  - Influenza A virus infection of vascular endothelial cells induces GSK-3beta
      mediated beta-catenin degradation in adherens junctions, with a resultant
      increase in membrane permeability.
AB  - Multiorgan failure with vascular hyperpermeability is the final outcome in the
      progression of seasonal influenza virus pneumonia and influenza-associated
      encephalopathy, and it is also common in infection with highly pathogenic avian
      influenza virus. However, the precise molecular mechanism by which influenza
      virus infection causes vascular endothelial cell hyperpermeability remains poorly
      defined. We investigated the mechanisms of hyperpermeability of human umbilical
      vein endothelial cells infected with influenza A virus (IAV)/Puerto Rico/8/34
      (PR8) (H1N1). The levels of beta-catenin, a key regulatory component of the
      vascular endothelial-cadherin cell adhesion complex, were markedly decreased
      during infection for 28 h, with increments of vascular hyperpermeability measured
      by transendothelial electrical resistance. Lactacystin (at 2 MUM), a proteasome
      inhibitor, inhibited the decrease in beta-catenin levels. Since the N-terminal
      phosphorylation of beta-catenin by glycogen synthase kinase (GSK)-3beta is the
      initiation step of proteasome-dependent degradation, we examined the effects of
      GSK-3beta suppression by RNA interference in endothelial cells. IAV-infection
      induced beta-catenin degradation was significantly inhibited in GSK-3beta
      knockdown cells, and transfection of cells with recombinant beta-catenin
      significantly suppressed IAV-induced hyperpermeability. These findings suggest
      that IAV infection induces GSK-3beta-mediated beta-catenin degradation in the
      adherens junctional complexes and induces vascular hyperpermeability. The in
      vitro findings of beta-catenin degradation and activation of GSK-3beta after IAV
      infection were confirmed in lungs of mice infected with IAV PR8 during the course
      of infection from day 0 to day 6. These results suggest that GSK-3beta-mediated
      beta-catenin degradation in adherens junctions is one of the key mechanisms of
      vascular hyperpermeability in severe influenza.

PMID- 25385176
TI  - Molecular characterization of infectious laryngotracheitis virus in naturally
      infected egg layer chickens in a multi-age flock in Brazil.
AB  - The virus responsible for an outbreak of infectious laryngotracheitis (ILT) in a
      multi-age flock of egg layer chickens under quarantine in Brazil was
      characterized. Layer chickens from this area with circulating gallid herpesvirus
      1 (GaHV 1) were evaluated using histopathology and molecular characterization
      techniques based on sequences of infected-cell polypeptide 4 (ICP4) and thymidine
      kinase (TK) genes. The infected chickens that were analyzed were PCR-positive for
      GaHV-1 in the trachea and negative in most trigeminal ganglia. The lack of ILT
      lesions in the conjunctiva and respiratory tissues, combined with detection of
      viral DNA in the trachea, was found to be associated with latent infection. The
      sequences from five farms obtained in the present study were identical, and there
      were no deletions within the 272- to 283-bp region of the ICP4 gene, as observed
      in the sequences of vaccine strains (CEO and TCO). The lack of a deletion in the
      ICP4 fragment analyzed in this study indicates that the chickens were infected
      with a field virus. The absence of the T252M mutation in a fragment of the TK
      gene, in addition to the low mortality rate observed, suggests that the outbreak
      in the state of Minas Gerais was not caused by a highly virulent strain but
      rather by a field virus of lower virulence. In addition, using phylogenetic
      reconstructions, it was found that this field strain was grouped together in a
      separate branch, apart from the previously characterized Brazilian strains. The
      introduction of vectored vaccines apparently has been effective in reducing
      clinical disease and lesions, and preventing new outbreaks of disease.

PMID- 25385177
TI  - Comparative genomic sequence analysis of Chinese orf virus strain NA1/11 with
      other parapoxviruses.
AB  - Orf virus (ORFV) is a typical member of the genus Parapoxvirus. The parapoxvirus
      genome consists of highly variable terminal regions and relatively conserved
      central regions with a high G + C content. In our previous study, a novel ORFV
      strain, NA1/11, was isolated from northeastern China. To fully characterize this
      strain, we sequenced the entire genome of NA1/11 and conducted a comparative
      analysis using multiple parapoxviruses. The genomic sequence of NA1/11 was found
      to consist of 137,080 nucleotides with a G + C content of 63.6 %, but it did not
      contain the terminal hairpin sequence. Alignment of ORFs from NA1/11 with NZ2,
      IA82 and SA00 revealed several highly variable ORFs, while the most evident ones
      are ORFs 001, 103, 109-110, 116 and 132. An odd phenomenon in the region of ORFs
      118-120 is that the non-coding fragments are almost as long as the coding
      fragments. By comparative analysis of inverted terminal repeats, we identified
      one repeat motif and a long conserved fragment. By comparing the ITRs of SA00
      with those of three other ORFVs, more clues were obtained about the correlation
      between ITR sequence and host adaption. Comparison of the NA1/11 genome with the
      sequences of other strains of ORFV revealed highly variable regions, thus
      providing new insights into the genetic diversity of ORFV.

PMID- 25385178
TI  - Concerns about methods for determination of estrogens in body fluids.

PMID- 25385179
TI  - Infection risk in breast cancer patients treated with trastuzumab: a systematic
      review and meta-analysis.
AB  - Infections related to anti-HER2 monoclonal antibodies (mAbs), trastuzumab and
      pertuzumab, have been reported in clinical trials. It is not yet clear whether
      these drugs increase an infection risk or not. We performed a systematic review
      and meta-analysis to assess the risk of infections associated with anti-HER2
      mAbs. We searched PubMed and the ASCO online database of meeting abstracts up to
      January 2014 for relevant clinical trials. Eligible studies included randomized
      controlled trials of trastuzumab or pertuzumab for breast cancer patients that
      reported adequate safety data for grade 3-4 infection, febrile neutropenia,
      neutropenia, or leukopenia. The summary incidence, relative risk (RR), and 95 %
      confidence intervals (CIs) were calculated. A total of 10,094 patients from 13
      trials were included. The use of trastuzumab was associated with an increased
      risk of high-grade infection (RR 1.21, 95 % CI 1.07-1.37, P = 0.002) and febrile
      neutropenia (RR 1.28, 95 % CI 1.08-1.52, P = 0.004). The incidence of high-grade
      infection and febrile neutropenia due to trastuzumab was 8.5 % (95 % CI 4.5-15.4
      %) and 12.0 % (95 % CI 8.1-17.4 %), respectively. There was no significant
      increase in a risk of high-grade neutropenia or leukopenia in patients receiving
      trastuzumab. Treatment with trastuzumab is associated with a significantly higher
      risk of high-grade infection and febrile neutropenia. Our findings suggest an
      importance of close monitoring for any signs of infections in patients treated
      with trastuzumab.

PMID- 25385180
TI  - Skin/nail infections with the addition of pertuzumab to trastuzumab-based
      chemotherapy.
AB  - We report a series of breast cancer patients with invasive skin and nail
      infections with Staphylococcus species that we attribute to the addition of
      pertuzumab to trastuzumab-based therapy. With the suspicion of an increased
      incidence of cutaneous infection in patients treated with pertuzumab and
      trastuzumab-based chemotherapy, treating medical oncologists identified patients
      receiving therapy who experienced infection. Between March and October 2014, 18
      patients treated with pertuzumab and trastuzumab-based chemotherapy were found to
      have 21 separate skin/nail infections. Treatment was administered as neoadjuvant
      therapy in 12 (67%) patients, adjuvant therapy in four (22%) patients, and for
      metastatic disease in two (11%) patients. Granulocyte growth factors were
      administered in 11 (61%) patients and no patients were documented to be
      neutropenic. New skin and nail lesions developed as early as cycle 1 and as late
      as 8 months from initial therapy. The 21 separate infections documented were
      folliculitis and "bite-like" lesions (10), abscess (6), paronychia (3), and
      cellulitis (2). The appearance of these lesions was distinct from typical EGFR
      associated skin changes. When cultures were obtained, Staphylococcus species were
      isolated. Quantitative immunoglobulins were assessed in 14 (78%) patients and
      were abnormally low in six (43%) of these patients. The skin infections resulted
      in treatment delay in two (11%) patients and premature discontinuation of therapy
      in one patient. We believe that the skin/nail infections reported here in
      patients treated with the combination of pertuzumab and trastuzumab represent a
      previously unrecognized toxicity of adding pertuzumab to trastuzumab-based
      therapies.

PMID- 25385181
TI  - Association of SULT1A1 Arg213His polymorphism with male breast cancer risk:
      results from a multicenter study in Italy.
AB  - Male breast cancer (MBC) is rare and poorly understood. Like female breast cancer
      (FBC), MBCs are highly sensitive to hormonal changes, and hyperestrogenism,
      specifically, represents a major risk factor for MBC. MBC is considered similar
      to late-onset, post-menopausal estrogen/progesteron receptors positive FBC
      (ER+/PR+). Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism
      of estrogens. Recently, SULT1A1 common functional polymorphism Arg(213)His
      (638G>A) variant has been found to be associated with increased breast cancer
      (BC) risk, particularly in post-menopausal women. For this reason, we decided to
      explore whether SULT1A1 Arg(213)His could exert an effect on MBC development. The
      primary aim of this study was to evaluate the influence of the SULT1A1
      Arg(213)His polymorphism on MBC risk. The secondary aim was to investigate
      possible associations with relevant clinical-pathologic features of MBC. A total
      of 394 MBC cases and 786 healthy male controls were genotyped for SULT1A1
      Arg(213)His polymorphism by PCR-RFLP and high-resolution melting analysis. All
      MBC cases were characterized for relevant clinical-pathologic features. A
      significant difference in the distribution of SULT1A1 Arg(213)His genotypes was
      found between MBC cases and controls (P < 0.0001). The analysis of genotype
      specific risk showed a significant increased MBC risk in individuals with G/A (OR
      1.97, 95% CI 1.50-2.59; P < 0.0001) and A/A (OR 3.09, 95% CI 1.83-5.23; P <
      0.0001) genotypes in comparison to wild-type genotype, under co-dominant model. A
      significant association between SULT1A1 risk genotypes and HER2 status emerged.
      Results indicate that SULT1A1 Arg(213)His may act as a low-penetrance risk allele
      for developing MBC and could be associated with a specific tumor subtype
      associated with HER2 overexpression.

PMID- 25385182
TI  - Dan Fletcher: a recipe for cooking up cellular machines.

PMID- 25385184
TI  - Glucose uptake in brown fat cells is dependent on mTOR complex 2-promoted GLUT1
      translocation.
AB  - Brown adipose tissue is the primary site for thermogenesis and can consume, in
      addition to free fatty acids, a very high amount of glucose from the blood, which
      can both acutely and chronically affect glucose homeostasis. Here, we show that
      mechanistic target of rapamycin (mTOR) complex 2 has a novel role in beta3
      adrenoceptor-stimulated glucose uptake in brown adipose tissue. We show that
      beta3-adrenoceptors stimulate glucose uptake in brown adipose tissue via a
      signaling pathway that is comprised of two different parts: one part dependent on
      cAMP-mediated increases in GLUT1 transcription and de novo synthesis of GLUT1 and
      another part dependent on mTOR complex 2-stimulated translocation of newly
      synthesized GLUT1 to the plasma membrane, leading to increased glucose uptake.
      Both parts are essential for beta3-adrenoceptor-stimulated glucose uptake.
      Importantly, the effect of beta3-adrenoceptor on mTOR complex 2 is independent of
      the classical insulin-phosphoinositide 3-kinase-Akt pathway, highlighting a novel
      mechanism of mTOR complex 2 activation.

PMID- 25385183
TI  - The contribution of alphabeta-tubulin curvature to microtubule dynamics.
AB  - Microtubules are dynamic polymers of alphabeta-tubulin that form diverse cellular
      structures, such as the mitotic spindle for cell division, the backbone of
      neurons, and axonemes. To control the architecture of microtubule networks,
      microtubule-associated proteins (MAPs) and motor proteins regulate microtubule
      growth, shrinkage, and the transitions between these states. Recent evidence
      shows that many MAPs exert their effects by selectively binding to distinct
      conformations of polymerized or unpolymerized alphabeta-tubulin. The ability of
      alphabeta-tubulin to adopt distinct conformations contributes to the intrinsic
      polymerization dynamics of microtubules. alphabeta-Tubulin conformation is a
      fundamental property that MAPs monitor and control to build proper microtubule
      networks. 

PMID- 25385185
TI  - Live cell micropatterning reveals the dynamics of signaling complexes at the
      plasma membrane.
AB  - Interactions of proteins in the plasma membrane are notoriously challenging to
      study under physiological conditions. We report in this paper a generic approach
      for spatial organization of plasma membrane proteins into micropatterns as a tool
      for visualizing and quantifying interactions with extracellular, intracellular,
      and transmembrane proteins in live cells. Based on a protein-repellent
      poly(ethylene glycol) polymer brush, micropatterned surface functionalization
      with the HaloTag ligand for capturing HaloTag fusion proteins and RGD peptides
      promoting cell adhesion was devised. Efficient micropatterning of the type I
      interferon (IFN) receptor subunit IFNAR2 fused to the HaloTag was achieved, and
      highly specific IFN binding to the receptor was detected. The dynamics of this
      interaction could be quantified on the single molecule level, and IFN-induced
      receptor dimerization in micropatterns could be monitored. Assembly of active
      signaling complexes was confirmed by immunostaining of phosphorylated Janus
      family kinases, and the interaction dynamics of cytosolic effector proteins
      recruited to the receptor complex were unambiguously quantified by fluorescence
      recovery after photobleaching. 

PMID- 25385186
TI  - pHuji, a pH-sensitive red fluorescent protein for imaging of exo- and
      endocytosis.
AB  - Fluorescent proteins with pH-sensitive fluorescence are valuable tools for the
      imaging of exocytosis and endocytosis. The Aequorea green fluorescent protein
      mutant superecliptic pHluorin (SEP) is particularly well suited to these
      applications. Here we describe pHuji, a red fluorescent protein with a pH
      sensitivity that approaches that of SEP, making it amenable for detection of
      single exocytosis and endocytosis events. To demonstrate the utility of the pHuji
      plus SEP pair, we perform simultaneous two-color imaging of clathrin-mediated
      internalization of both the transferrin receptor and the beta2 adrenergic
      receptor. These experiments reveal that the two receptors are differentially
      sorted at the time of endocytic vesicle formation.

PMID- 25385188
TI  - Drug-drug interactions of telaprevir and boceprevir in HCV-monoinfected and
      HIV/HCV-coinfected patients can modify the adherence.
AB  - BACKGROUND & AIMS: The first generation protease inhibitors, boceprevir (BOC) and
      telaprevir (TVR), are both CYP3A4 inhibitors, which predispose drug-drug
      interactions (DDIs). The aim of this study was to evaluate the prevalence of
      potential DDIs, the management of outpatient medication and its impact on
      adherence and efficacy to antiviral treatment in hepatitis C virus (HCV)
      monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients
      receiving BOC and TVR. METHODS: The usual medication starting with BOC or TVR was
      screened by the pharmacist of the multidisciplinary support programme (MSP) for
      potential DDIs. Recommendations were made to avoid significant DDIs, and changes
      in the baseline medication were recorded. Adherence to antiviral treatment was
      considered as 80/80/95% of total doses. Sustained virological response was
      assessed at week 12 (SVR12). RESULTS: At least one potential DDI was found in 70
      (64.8%) patients, 45 (54.2%) being HCV-monoinfected and 25 (100%) HIV/HCV
      coinfected (P < 0.01). Baseline treatment modifications were required in 38
      (35.2%) patients. Adherence and SVR12 were higher in patients without DDIs
      (86.8%) and (67.6%) compared to those with DDIs (62.8%) (P = 0.021) and (47.2%)
      (P = 0.097) respectively. CONCLUSIONS: More than half of the patients were at
      risk of presenting DDIs, leading to changes in the baseline medication in one
      third of the patients. Drug interactions are frequent in patients with lower
      adherence.

PMID- 25385187
TI  - Fibrosis, vascular activation, and immune abnormalities resembling systemic
      sclerosis in bleomycin-treated Fli-1-haploinsufficient mice.
AB  - OBJECTIVE: Fli-1, a potential predisposing factor for systemic sclerosis (SSc),
      is constitutively down-regulated in the lesional skin of patients with SSc by an
      epigenetic mechanism. To investigate the impact of Fli-1 deficiency on the
      induction of an SSc phenotype in various cell types, we generated bleomycin
      induced skin fibrosis in Fli-1(+/-) mice and investigated the molecular
      mechanisms underlying its phenotypic alterations. METHODS: Messenger RNA (mRNA)
      levels and protein expression of target molecules were examined by quantitative
      reverse transcription-polymerase chain reaction and immunostaining. Transforming
      growth factor beta (TGFbeta) bioassay was used to evaluate the activation of
      latent TGFbeta. The binding of Fli-1 to the target gene promoters was assessed
      with chromatin immunoprecipitation. RESULTS: Bleomycin induced more severe dermal
      fibrosis in Fli-1(+/-) mice than in wild-type mice. Fli-1 haploinsufficiency
      activated dermal fibroblasts via the up-regulation of alphavbeta3 and alphavbeta5
      integrins and activation of latent TGFbeta. Dermal fibrosis in Fli-1(+/-) mice
      was also attributable to endothelial-to-mesenchymal transition, which is directly
      induced by Fli-1 deficiency and amplified by bleomycin. Th2/Th17-skewed
      inflammation and increased infiltration of mast cells and macrophages were seen,
      partly due to the altered expression of cell adhesion molecules in endothelial
      cells as well as the induction of the skin chemokines. Fli-1(+/-) mouse
      macrophages preferentially differentiated into an M2 phenotype upon stimulation
      with interleukin-4 (IL-4) or IL-13. CONCLUSION: Our findings provide strong
      evidence for the fundamental role of Fli-1 deficiency in inducing SSc-like
      phenotypic alterations in dermal fibroblasts, endothelial cells, and macrophages
      in a manner consistent with human disease.

PMID- 25385189
TI  - Combination effect of photodynamic therapy using NPe6 with pemetrexed for human
      malignant pleural mesothelioma cells.
AB  - To identify a possible new treatment modality for malignant pleural mesothelioma
      (MPM), we examined whether combination treatment consisting of pemetrexed
      chemotherapy and photodynamic therapy (PDT) using the photosensitizer NPe6,
      enhanced the antitumor effect in both in vitro and in vivo models. We also
      investigated preclinical treatment schedules. Four human malignant mesothelioma
      cell lines (MSTO-211H, H2052, H2452 and H28) were assayed using the WST assay
      after treatment with pemetrexed and NPe6-PDT. The treatment schedule for the
      combination treatment was examined using nude mice. Pemetrexed pre-treatment
      enhanced the lethal effect of NPe6-PDT in the four malignant mesothelioma cell
      lines, but NPe6-PDT followed by pemetrexed treatment did not enhance cell
      lethality in the in vitro assay. Pemetrexed pre-treatment did not enhance the
      intracellular accumulation of NPe6, which is one of the determinants of the
      antitumor effect of PDT. In nude mice injected with MSTO-211H cells and then
      treated using a combination of pemetrexed and NPe6-PDT (10 mg/kg NPe6, 10 J/cm(2)
      laser irradiation), the tumor volume decreased by 50% but subsequently increased,
      reaching the pre-treatment value after 14 days. Pemetrexed treatment followed by
      NPe6-PDT resulted in an 80% reduction in the tumor size and inhibited re-growth.
      NPe6-PDT followed by pemetrexed treatment resulted in a 60% reduction in tumor
      size but did not inhibit re-growth. NPe6-PDT induced the expression of
      thymidylate synthase (TS), which confers resistance to pemetrexed, and NPe6-PDT
      followed by pemetrexed treatment did not enhance the treatment outcome in vivo.
      In conclusion, combination treatment, consisting of pemetrexed followed by NPe6
      PDT, should be further investigated as a new treatment modality for MPM. In the
      future, this combination treatment may contribute to a reduction in local
      recurrence and a prolonged survival period in patients with MPM.

PMID- 25385190
TI  - A comparison of different models with motor dysfunction after traumatic brain
      injury in adult rats.
AB  - The aim of this study was to evaluate the validity of the model that could
      produce reproducible and persistent motor weakness and define the accurate tasks
      and testing parameters for longitudinal assessment of neurological deficits after
      traumatic brain injury (TBI). We compared the effects of two rat models that
      suffered different controlled cortical impact (CCI) injury, as well as extensive
      motor cortex resection model, on behavior recovery and brain morphology.
      Behavioral tests including the skilled reaching task, limb-use asymmetry test and
      the grasping test were employed to evaluate neurofunctional recovery from pre- to
      12 weeks after the injury. The results demonstrated that all the rats in four
      groups showed spontaneous functional improvement with the past of time after
      surgery, especially in rats with mild and moderate CCI injury. At the end of the
      experiment, the animals' performance reached preoperative base lines on reaching
      task and limb-use asymmetry test in mild and moderate groups, while severe motor
      weakness could be observed in rats with severe CCI injury, as well as rats with
      extended motor cortex resection. Overall, the results of this study indicated
      that both models with severe CCI injury and extended resection of the motor
      cortex developed reproducible and long-lasting motor weakness, comparable in
      severity and duration and identified skilled reaching task, as well as limb-use
      asymmetry test, as sensitive assessments for slight neurological deficits after
      brain injury. This will help to provide the basis for further research of the
      processes after the TBI and development of novel therapies. 

PMID- 25385191
TI  - Improved reaction conditions for the synthesis of new NKP-1339 derivatives and
      preliminary investigations on their anticancer potential.
AB  - The very promising results of Na-trans-[RuCl4(1H-indazole)2] (NKP-1339) in
      clinical studies have fuelled renewed interest in the research and development of
      ruthenium(III) coordination compounds for cancer therapy. By applying an improved
      synthetic approach to this class of coordination compounds, six new examples of
      the general formula (cation)-trans-[RuCl4(azole)2], where (cation) =
      tetrabutylammonium (Bu4N)(+) (1, 2), sodium (3, 4), azolium (5, 6), and azole = 1
      methyl-indazole (1, 3, 5), 1-ethyl-indazole (2, 4, 6), have been prepared. All
      compounds have been characterized by elemental analysis, electrospray ionization
      (ESI) mass spectrometry, UV-vis-, and NMR-spectroscopy and, if possible, X-ray
      diffraction analysis. Furthermore, the influence of the alkyl substituent at the
      position N1 of the indazole backbone on the stability in aqueous media as well as
      on the biological activity in three human cancer cell lines (CH1, A549, and
      SW480) and on the cellular accumulation in SW480 cells is discussed.

PMID- 25385194
TI  - A comparison of seven methods for continuous therapeutic cooling of the equine
      digit.
AB  - REASONS FOR PERFORMING STUDY: Digital hypothermia may be effective for laminitis
      prophylaxis and therapy, but the efficacy of cooling methods used in clinical
      practice requires evaluation. OBJECTIVES: To use hoof wall surface temperature
      (HWST) to compare several cooling methods used in clinical practice. STUDY
      DESIGN: Experimental crossover design with a minimum washout period of 72 h.
      METHODS: Seven cooling methods (commercially available ice packs, wraps and
      boots) and one prototypical dry-sleeve device were applied to a single forelimb
      in 4 horses for 8 h, during which HWST of the cooled forelimb and the uncooled
      (control) forelimb was recorded hourly. Results were analysed descriptively.
      RESULTS: The median (range) HWST from 2-8 h was lowest for the ice and water
      immersion methods that included the foot and extended proximally to at least
      include the pastern: 5.2 degrees C (range: 4.8-7.8 degrees C) for the fluid bag
      and 2.7 degrees C (2.4-3.4 degrees C) for the ice boot. An ice boot that included
      the distal limb but not the foot resulted in a median HWST of 25.7 degrees C
      (20.6-27.2 degrees C). Dry interface applications (ice packs) confined to the
      foot only resulted in a median HWST of 21.5 degrees C (19.5-25.5 degrees C) for
      the coronet sleeve and 19.8 degrees C (17.6-23 degrees C) for a commercial ice
      pack. For the dry interface applications that included the foot and distal limb,
      the median HWST was much higher for the ice pack device, 19.9 degrees C (18.7
      23.1 degrees C), compared with the perfused cuff prototype of 5.4 degrees C (4.2
      7 degrees C). CONCLUSIONS: Immersion of the foot and at least the pastern region
      in ice and water achieved sustained HWST <10 degrees C as did a prototype
      perfused cuff device with a dry interface. Variation between cooling methods may
      have a profound effect on HWST and therefore efficacy in clinical cases where
      laminitis prophylaxis or therapy is the goal.

PMID- 25385192
TI  - Variants in CUL4B are associated with cerebral malformations.
AB  - Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked
      intellectual disability. Here, we describe an additional 25 patients from 11
      families with variants in CUL4B. We identified nine different novel variants in
      these families and confirmed the pathogenicity of all nontruncating variants.
      Neuroimaging data, available for 15 patients, showed the presence of cerebral
      malformations in ten patients. The cerebral anomalies comprised malformations of
      cortical development (MCD), ventriculomegaly, and diminished white matter volume.
      The phenotypic heterogeneity of the cerebral malformations might result from the
      involvement of CUL-4B in various cellular pathways essential for normal brain
      development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in
      which variants were previously identified in patients with microcephaly and a
      wide range of MCD. This interaction might contribute to the development of
      cerebral malformations in patients with variants in CUL4B. 

PMID- 25385195
TI  - The aetiology of neonatal seizures and the diagnostic contribution of neonatal
      cerebral magnetic resonance imaging.
AB  - AIM: The aim of this study was to delineate aetiologies and explore the
      diagnostic value of cerebral magnetic resonance imaging (MRI) in addition to
      cranial ultrasonography (cUS) in infants presenting with neonatal seizures.
      METHOD: This retrospective cohort study comprised infants (gestational age 35.0
      42.6wks) with seizures, confirmed by either continuous amplitude-integrated
      electroencephalography (aEEG) or standard EEG and admitted during a 14-year
      period to a level three neonatal intensive care unit (n=378; 216 males, 162
      females; mean [SD] birthweight 3334g [594]). All infants underwent cUS and MRI
      (MRI on median of 5 days after birth, range 0-58d) within the first admission
      period. RESULTS: An underlying aetiology was identified in 354 infants (93.7%).
      The most common aetiologies identified were hypoxic-ischaemic encephalopathy
      (46%), intracranial haemorrhage (12.2%), and perinatal arterial ischaemic stroke
      (10.6%). When comparing MRI with cUS in these 354 infants MRI showed new findings
      which did not become apparent on cUS, contributing to a diagnosis in 42 (11.9%)
      infants and providing additional information to cUS, contributing to a diagnosis
      in 141 (39.8%). cUS alone would have allowed a diagnosis in only 37.9% of infants
      (134/354). INTERPRETATION: Cerebral MRI contributed to making a diagnosis in the
      majority of infants. In 11.9% of infants the diagnosis would have been missed if
      only cUS were used and cerebral MRI added significantly to the information
      obtained in 39.8% of infants. These data suggest that cerebral MRI should be
      performed in all newborn infants presenting with EEG- or aEEG-confirmed seizures.

PMID- 25385196
TI  - Airway branching has conserved needs for local parasympathetic innervation but
      not neurotransmission.
AB  - BACKGROUND: Parasympathetic signaling has been inferred to regulate epithelial
      branching as well as organ regeneration and tumor development. However, the
      relative contribution of local nerve contact versus secreted signals remains
      unclear. Here, we show a conserved (vertebrates to invertebrates) requirement for
      intact local nerves in airway branching, persisting even when cholinergic
      neurotransmission is blocked. RESULTS: In the vertebrate lung, deleting enhanced
      green fluorescent protein (eGFP)-labeled intrinsic neurons using a two-photon
      laser leaves adjacent cells intact, but abolishes branching. Branching is
      unaffected by similar laser power delivered to the immediately adjacent non
      neural mesodermal tissue, by blocking cholinergic receptors or by blocking
      synaptic transmission with botulinum toxin A. Because adjacent vasculature and
      epithelial proliferation also contribute to branching in the vertebrate lung, the
      direct dependence on nerves for airway branching was tested by deleting neurons
      in Drosophila embryos. A specific deletion of neurons in the Drosophila embryo by
      driving cell-autonomous RicinA under the pan-neuronal elav enhancer perturbed
      Drosophila airway development. This system confirmed that even in the absence of
      a vasculature or epithelial proliferation, airway branching is still disrupted by
      neural lesioning. CONCLUSIONS: Together, this shows that airway morphogenesis
      requires local innervation in vertebrates and invertebrates, yet
      neurotransmission is dispensable. The need for innervation persists in the fly,
      wherein adjacent vasculature and epithelial proliferation are absent. Our novel,
      targeted laser ablation technique permitted the local function of parasympathetic
      innervation to be distinguished from neurotransmission.

PMID- 25385197
TI  - Educational attainment and ability in young adults following acquired brain
      injury.
AB  - PURPOSE: To compare the educational levels of clients with brain injury, acquired
      during working age who received neurorehabilitation between 2002 and 2013 with
      two governmental reports examining educational levels of attainment in the
      general public. METHODS: Results from national skills numeracy and literacy
      assessments undertaken by clients with acquired brain injury (ABI) on admission
      to the centre between 2002 and 2013 were compared with the results from two
      national reports examining educational attainment in people in further education
      with and without long term disabilities, as part of an ongoing review/audit of
      the service. RESULTS: ABI resulted in lower levels of literacy and numeracy
      compared to the general public; women with ABI performed more poorly on the
      numeracy assessment compared to the literacy assessment; and clients with ABI had
      a disproportionately reduced level of literacy, resulting in a more even pattern
      of attainment on the numeracy and literacy assessments whereas the general public
      scored more highly on the literacy assessment. CONCLUSION: ABI adversely affects
      both literacy and numeracy skills. It is important that the effect of ABI on
      numeracy and literacy is considered during vocational counselling and
      rehabilitation as a person's premorbid education level may be an overestimation
      of their abilities.

PMID- 25385198
TI  - Implementing a self-management intervention for people with a chronic compensable
      musculoskeletal injury in a workers compensation context: a process evaluation.
AB  - PURPOSE: Determining factors critical for an intervention's success, specifically
      for whom and under what circumstances, is necessary if interventions are to be
      effectively targeted and efficiently implemented. This paper describes a process
      evaluation undertaken to assess the implementation of a novel self-management
      (SM) intervention developed for those with a chronic compensable work-related
      musculoskeletal disorder seeking to return to work. METHODS: The process
      evaluation, assessing the 'Self-Management for Return to Work' intervention,
      examined data from program leader evaluations, telephone interviews with
      stakeholders (injured worker participants, vocational rehabilitation consultant
      program leaders and compensation insurance regulators), post-intervention focus
      group session feedback, attendance lists and researcher notes. RESULTS: The
      evaluation identified several challenges and barriers associated with conducting
      research within the VR environment and with the characteristics of those targeted
      i.e., injured workers with a chronic compensable condition. These issues were
      primary contributing factors to the modifications to the randomised controlled
      trial methodology and the trial's premature cessation. CONCLUSIONS: Despite the
      difficulties encountered, high stakeholder acceptability suggests that the
      concept and theory underlying the targeted SM intervention were not flawed,
      though there is room for further tailoring to both the program method and its
      timing. The results of this process evaluation provide a useful platform for
      others considering the implementation of interventions within the vocational
      rehabilitation context or with individuals with chronic, compensated injuries.

PMID- 25385199
TI  - The Management of Long-Term Sickness Absence in Large Public Sector Healthcare
      Organisations: A Realist Evaluation Using Mixed Methods.
AB  - PURPOSE: The success of measures to reduce long-term sickness absence (LTSA) in
      public sector organisations is contingent on organisational context. This realist
      evaluation investigates how interventions interact with context to influence
      successful management of LTSA. METHODS: Multi-method case study in three Health
      and Social Care Trusts in Northern Ireland comprising realist literature review,
      semi-structured interviews (61 participants), Process-Mapping and feedback
      meetings (59 participants), observation of training, analysis of documents.
      RESULTS: Important activities included early intervention; workplace-based
      occupational rehabilitation; robust sickness absence policies with clear trigger
      points for action. Used appropriately, in a context of good interpersonal and
      interdepartmental communication and shared goals, these are able to increase the
      motivation of staff to return to work. Line managers are encouraged to take a
      proactive approach when senior managers provide support and accountability.
      Hindering factors: delayed intervention; inconsistent implementation of policy
      and procedure; lack of resources; organisational complexity; stakeholders
      misunderstanding each other's goals and motives. CONCLUSIONS: Different
      mechanisms have the potential to encourage common motivations for earlier return
      from LTSA, such as employees feeling that they have the support of their line
      manager to return to work and having the confidence to do so. Line managers'
      proactively engage when they have confidence in the support of seniors and in
      their own ability to address LTSA. Fostering these motivations calls for a
      thoughtful, diagnostic process, taking into account the contextual factors (and
      whether they can be modified) and considering how a given intervention can be
      used to trigger the appropriate mechanisms.

PMID- 25385200
TI  - Return to Work After Temporary Disability Pension in Finland.
AB  - PURPOSE: When it is possible that the employee's work ability can be restored
      through treatment or rehabilitation, disability pension in Finland is granted for
      a fixed period. We examined which factors are associated with return to work
      (RTW) after such temporary disability pension. METHODS: The study included all
      Finnish residents whose temporary disability pension from the earnings-related
      pension system started in 2008 (N = 10,269). Competing risks regression analysis
      was applied to examine register-based determinants for RTW after temporary
      disability pension due to mental disorders, musculoskeletal diseases, other
      diseases, and injury over a 4-year follow-up period. RESULTS: The overall
      cumulative incidence of RTW was 25%. RTW was more probable after temporary
      disability pension due to injury and musculoskeletal diseases and less probable
      after temporary disability pension due to mental disorders. Younger age and
      higher education increased RTW but differences between genders, private and
      public sector employees, and occupational classes were relatively small. The
      probability of RTW was higher among those who were employed before their
      temporary disability pension (subhazard ratio in multivariate analysis 2.41 (95%
      CI 2.13-2.72) and among the 9% who participated in vocational rehabilitation
      during their pension [SHR 2.10 (95% CI 1.90-2.31)]. With some exceptions, the
      results were fairly similar for all diagnostic causes of temporary disability
      pension. CONCLUSION: Return to work after temporary disability pension was
      relatively uncommon. Nevertheless, in all diagnostic groups RTW continued for the
      whole follow-up period. The low educated and those not employed before temporary
      disability pension need more support in their RTW. The strong association between
      vocational rehabilitation and RTW suggests that increasing rehabilitation among
      those with impaired work ability may promote RTW.

PMID- 25385201
TI  - Construct Validity of Functional Capacity Evaluation in Patients with Whiplash
      Associated Disorders.
AB  - PURPOSE: The construct validity of functional capacity evaluations (FCE) in
      whiplash-associated disorders (WAD) is unknown. The aim of this study was to
      analyse the validity of FCE in patients with WAD with cultural differences within
      a workers' compensation setting. METHODS: 314 participants (42% females, mean age
      36.7 years) with WAD (grade I and II) were referred for an interdisciplinary
      assessment that included FCE tests. Four FCE tests (hand grip strength, lifting
      waist to overhead, overhead working, and repetitive reaching) and a number of
      concurrent variables such as self-reported pain, capacity, disability, and
      psychological distress were measured. To test construct validity, 29 a priori
      formulated hypotheses were tested, 4 related to gender differences, 20 related
      associations with other constructs, 5 related to cultural differences. RESULTS:
      Men had significantly more hand grip strength (+17.5 kg) and lifted more weight
      (+3.7 kg): two out of four gender-related hypotheses were confirmed. Correlation
      between FCE and pain ranged from -0.39 to 0.31; FCE and self-reported capacity
      from -0.42 to 0.61; FCE and disability from -0.45 to 0.34; FCE and anxiety from 
      0.36 to 0.27; and FCE and depression from -0.41 to 0.34: 16 of 20 hypotheses
      regarding FCE and other constructs were confirmed. FCE test results between the
      cultural groups differed significantly (4 hypotheses confirmed) and effect size
      (ES) between correlations were small (1 hypothesis confirmed). In total 23 out of
      29 hypotheses were confirmed (79%). CONCLUSIONS: The construct validity for
      testing functional capacity was confirmed for the majority of FCE tests in
      patients with WAD with cultural differences and in a workers' compensation
      setting. Additional validation studies in other settings are needed for
      verification.

PMID- 25385202
TI  - Do Assessments of HIV Risk Behaviors Change Behaviors and Prevention Intervention
      Efficacy? An Experimental Examination of the Influence of Type of Assessment and
      Risk Perceptions.
AB  - BACKGROUND: Behavioral assessments may change behaviors and responses to
      behavioral interventions, depending on assessment type and respondents'
      motivations. PURPOSE: We observed effects on sexual behavior and human
      immunodeficiency virus (HIV) prevention intervention efficacy of interviews
      assessing recent HIV risk behavior frequency or HIV risk behavior events among
      respondents with different perceptions of their risk for HIV. METHODS: Young
      South African sexually transmitted infection (STI) clinic clients (N=1,728)
      participated in a 3 (event-based vs. frequency-based vs. no interview) by 2
      (evidence-based vs. standard of care risk-reduction session) RCT. RESULTS: The
      interviews increased reported safer sexual behavior among youth with higher but
      not lower risk perceptions. The intervention session was less effective when
      combined with interviews, particularly among lower risk perception youth.
      Patterns replicated for both interviews. CONCLUSIONS: HIV risk behavior
      assessments may increase resistance to interventions among unmotivated youth and
      enhance safer sexual behavior among motivated youth. Behavioral assessments may
      reduce HIV risk among motivated individuals.

PMID- 25385203
TI  - The Results of the "Positive Action for Today's Health" (PATH) Trial for
      Increasing Walking and Physical Activity in Underserved African-American
      Communities.
AB  - BACKGROUND: The "Positive Action for Today's Health" (PATH) trial tested an
      environmental intervention to increase walking in underserved communities.
      METHODS: Three matched communities were randomized to a police-patrolled walking
      plus social marketing, a police-patrolled walking-only, or a no-walking
      intervention. The 24-month intervention addressed safety and access for physical
      activity (PA) and utilized social marketing to enhance environmental supports for
      PA. African-Americans (N=434; 62% females; aged 51+/-16 years) provided
      accelerometry and psychosocial measures at baseline and 12, 18, and 24 months.
      Walking attendance and trail use were obtained over 24 months. RESULTS: There
      were no significant differences across communities over 24 months for moderate-to
      vigorous PA. Walking attendance in the social marketing community showed an
      increase from 40 to 400 walkers per month at 9 months and sustained ~200 walkers
      per month through 24 months. No change in attendance was observed in the walking
      only community. CONCLUSIONS: Findings support integrating social marketing
      strategies to increase walking in underserved African-Americans
      (ClinicalTrials.gov #NCT01025726).

PMID- 25385205
TI  - Synthesis of [13C4]-labeled 2'-deoxymugineic acid.
AB  - The phytosiderophore 2'-deoxymugineic acid (DMA) is exuded via the root system by
      all grasses (including important crop plants like rice, wheat and barley) to
      mobilize Fe(III) from soil and improve plant Fe nutrition, crucial for high crop
      yields. Elucidation of the biogeochemistry of 2'-deoxymugineic acid in the
      rhizosphere requires its quantification in minute amounts. To this end, (13)C4
      DMA was synthesized for the first time, from cheap isotopically labeled starting
      materials. The synthetic route utilizes L-allyl((13)C2)glycine and L-(2
      (13)C)azetidine ((13)C)carboxylic acid as versatile labeled building blocks. The
      title compound was recently used as an internal standard for analysis of soil and
      plant samples allowing the first accurate quantification of DMA in these matrices
      by means of LC-MS/MS. It is furthermore used in tracer experiments investigating
      biodegradation of DMA in soil.

PMID- 25385204
TI  - The ABCs of Trait Anger, Psychological Distress, and Disease Severity in HIV.
AB  - BACKGROUND: Trait anger consists of affective, behavioral, and cognitive (ABC)
      dimensions and may increase vulnerability for interpersonal conflict, diminished
      social support, and greater psychological distress. The concurrent influence of
      anger and psychosocial dysfunction on Human Immunodeficiency Virus (HIV) disease
      severity is unknown. PURPOSE: The purpose of this study was to examine plausible
      psychosocial avenues (e.g., coping, social support, psychological distress),
      whereby trait anger may indirectly influence HIV disease status. METHODS: Three
      hundred seventy-seven HIV seropositive adults, aged 18-55 years (58% AIDS
      defined), completed a battery of psychosocial surveys and provided a fasting
      blood sample for HIV-1 viral load and T lymphocyte count assay. RESULTS: A second
      order factor model confirmed higher levels of the multidimensional anger trait,
      which was directly associated with elevated psychological distress and avoidant
      coping (p<.001) and indirectly associated with greater HIV disease severity
      (p<.01) (comparative fit index (CFI)=0.90, root-mean-square error of
      approximation (RMSEA)=0.06, standardized root-mean-square residual (SRMR)=0.06).
      CONCLUSION: The model supports a role for the ABC components of anger, which may
      negatively influence immune function through various psychosocial mechanisms;
      however, longitudinal study is needed to elucidate these effects.

PMID- 25385206
TI  - Comparing the effectiveness of nasal dilator strips: does race play a role?
AB  - BACKGROUND: Nasal dilator strips are thought to widen and stiffen the anterior
      nasal cavity, and thus improve symptoms of nasal obstruction. It is postulated
      that anthropomorphic differences in external nasal proportions between races may
      influence the effectiveness of such dilator strips. METHODS: Caucasian and Asian
      subjects were compared. Nasal peak inspiratory flow, nasal airway resistance,
      minimum cross-sectional area and visual analogue scale measurements of nasal
      obstruction were recorded at baseline and following the application of two
      different dilator strips. RESULTS: Nine Caucasian and six Asian subjects were
      recruited (n = 15). There was a significant difference between races in terms of
      nasal peak inspiratory flow improvements following nasal strip application (mean
      of 29.4 litres per minute in Caucasians vs 14.6 litres per minute in Asians; p =
      0.04). Only Caucasians experienced a significant decrease in nasal airway
      resistance (median of 0.12 Pa/cm3/s; p < 0.01). CONCLUSION: Nasal peak
      inspiratory flow, minimum cross-sectional area and visual analogue scale values
      improved from baseline with strip application in both populations. Only
      Caucasians experienced significant nasal airway resistance improvement with strip
      application. Both cohorts experienced nasal peak inspiratory flow improvement,
      with Caucasians experiencing a significantly larger improvement.

PMID- 25385207
TI  - Overcoming challenges to teamwork in patient-centered medical homes: a
      qualitative study.
AB  - BACKGROUND: There is emerging consensus that enhanced inter-professional teamwork
      is necessary for the effective and efficient delivery of primary care, but there
      is less practical information specific to primary care available to guide
      practices on how to better work as teams. OBJECTIVE: The purpose of this study
      was to describe how primary care practices have overcome challenges to providing
      team-based primary care and the implications for care delivery and policy.
      APPROACH: Practices for this qualitative study were selected from those
      recognized as patient-centered medical homes (PCMHs) via the most recent National
      Committee for Quality Assurance PCMH tool, which included a domain on practice
      teamwork. PARTICIPANTS: Sixty-three respondents, ranging from physicians to front
      desk staff, were interviewed from May through December of 2013. Practice
      respondents came from 27 primary care practices ranging in size, type, geography,
      and population served. KEY RESULTS: Practices emphasizing teamwork overcame
      common challenges through the incremental delegation of non-clinical tasks away
      from physicians. The roles of medical assistants and nurses are expanding to
      include template-guided information collection from patients prior to the
      physician office visit as well as many other tasks. The inclusion of staff input
      in care workflow redesign and the use of data to demonstrate how team care
      process changes improved patient care were helpful in gaining staff buy-in. Team
      "huddles" guided by pre-visit planning were reported to assist in role
      delegation, consistency of information collected from patients, and structured
      communication among team members. Nurse care managers were found to be important
      team members in working with patients and their physicians on care plan design
      and execution. Most practices had not participated in formal teamwork training,
      but respondents expressed a desire for training for key team members,
      particularly if they could access it on-site (e.g., via practice coaches or the
      Internet). CONCLUSIONS: Participants who adopted new forms of delegation and care
      processes using teamwork approaches, and who were supported with resources,
      system support, and data feedback, reported improved provider satisfaction and
      productivity. There appears to be a need for more on-site teamwork training.

PMID- 25385208
TI  - Big plans, poor execution: the importance of governmental managerial innovation
      to health care reform.

PMID- 25385209
TI  - The future as a series of transitions: qualitative study of heart failure
      patients and their informal caregivers.
AB  - BACKGROUND: Advance care planning often only focuses on written advance
      directives rather than on future goals important to patients and families. Heart
      failure has a particularly uncertain future with variable clinical trajectories.
      A better understanding of patient and family concerns about and perceptions of
      the future could improve advance care planning. OBJECTIVE: We aimed to identify
      how patients with heart failure and their informal (family) caregivers perceive
      their future. DESIGN: This was a cross-sectional study using qualitative methods.
      PARTICIPANTS: Thirty-three patients from an academic health care system with New
      York Heart Association class II-IV heart failure and 20 of their informal
      caregivers participated in the study. We used a purposive sampling strategy to
      include patients within a range of ages and health statuses. APPROACH:
      Participants were asked in individual, semi-structured interviews: "When you
      think about what lies ahead, what comes to mind?" Qualitative analysis used an
      inductive approach. Early in the analysis, it became clear that participants'
      narratives about the future were described in terms of past transitions. This led
      us to use transition theory to further guide analysis. Transition theory
      describes how people restructure their reality and resolve uncertainty during
      change. KEY RESULTS: Patients and their caregivers talked about past and present
      transitions when asked about the future: "The present gets in the way of talking
      about the future." We identified four common pivotal transitions, including the
      shock of first being diagnosed with heart failure; learning to adjust to life
      with heart failure; reframing and taking back control of one's life; and
      understanding and accepting that death is inevitable. Concerns about the future
      were framed based on the most recent transition. CONCLUSIONS: Heart failure is a
      series of transitions according to patients and caregivers. By recognizing and
      educating patients about transitions, identifying transition-specific concerns,
      and supporting patients and caregivers through transitions, the process of
      planning for the future as part of advance care planning may be improved.

PMID- 25385210
TI  - You, me, and the computer makes three: navigating the doctor-patient relationship
      in the age of electronic health records.

PMID- 25385211
TI  - Capsule commentary on Ingebrigsten et al., Low use and adherence to maintenance
      medication in chronic obstructive pulmonary disease in the general population.

PMID- 25385212
TI  - Structural, evolutionary and functional analysis of the NAC domain protein family
      in Eucalyptus.
AB  - NAC domain transcription factors regulate many developmental processes and stress
      responses in plants and vary widely in number and family structure. We analysed
      the characteristics and evolution of the NAC gene family of Eucalyptus grandis, a
      fast-growing forest tree in the rosid order Myrtales. NAC domain genes identified
      in the E. grandis genome were subjected to amino acid sequence, phylogenetic and
      motif analyses. Transcript abundance in developing tissues and abiotic stress
      conditions in E. grandis and E. globulus was quantified using RNA-seq and reverse
      transcription quantitative PCR (RT-qPCR). One hundred and eighty-nine E. grandis
      NAC (EgrNAC) proteins, arranged into 22 subfamilies, are extensively duplicated
      in subfamilies associated with stress response. Most EgrNAC genes form tandem
      duplicate arrays that frequently carry signatures of purifying selection. Sixteen
      amino acid motifs were identified in EgrNAC proteins, eight of which are enriched
      in, or unique to, Eucalyptus. New candidates for the regulation of normal and
      tension wood development and cold responses were identified. This first
      description of a Myrtales NAC domain family reveals an unique history of tandem
      duplication in stress-related subfamilies that has likely contributed to the
      adaptation of eucalypts to the challenging Australian environment. Several new
      candidates for the regulation of stress, wood formation and tree-specific
      development are reported.

PMID- 25385213
TI  - Emotional processing and executive functions in major depressive disorder: dorsal
      prefrontal activity correlates with performance in the intra-extra dimensional
      set shift.
AB  - Heinzel A, Northoff G, Boeker H, Boesiger P, Grimm S. Emotional processing and
      executive functions in major depressive disorder: dorsal prefrontal activity
      correlates with performance in the intra-extra dimensional set shift. OBJECTIVE:
      Major depressive disorder (MDD) is characterised by predominately negatively
      valenced emotional symptoms that are often accompanied by cognitive impairments.
      We posited that cognitive impairments in MDD are related to altered emotional
      processing in prefrontal cortex. METHODS: We compared 20 medication-free patients
      with MDD and 29 matched healthy controls. Both groups performed an emotional task
      during functional magnetic resonance imaging (fMRI). Furthermore, they completed
      the intra-extra dimensional set shift (IED) test probing for cognitive
      impairments. Then we correlated the results of the IED with the changes in fMRI
      BOLD signal in MDD patients and healthy subjects. RESULTS: The subcategory of the
      IED applying extradimensional shift (EDS) showed a divergent performance of the
      MDD group committing significantly more errors than the control group.
      Correlating the EDS errors with fMRI signal changes, the healthy subjects showed
      a positive correlation with the right ventrolateral prefrontal cortex and the
      right orbitofrontal cortex. MDD subjects, in contrast, showed a positive
      correlation in right dorsolateral prefrontal cortex (DLPFC) and a negative
      correlation in the left dorsomedial prefrontal cortex (DMPFC). CONCLUSION: We
      hypothesise that the differential correlation in healthy controls and MDD
      patients may reflect the use of different strategies in their performance. The
      impaired executive functions, as reflected by altered processing in right DLPFC
      and left DMPFC, may implicitly influence emotional processing in patients
      suffering from MDD.

PMID- 25385214
TI  - A comparison of the symptomatic profile between two consecutive depressive
      episodes in patients with bipolar disorder type I.
AB  - de Macedo-Soares MB, Brietzke E, da Silva Dias R, Mendonca T, Moreira C, Lafer B.
      A comparison of the symptomatic profile between two consecutive depressive
      episodes in patients with bipolar disorder type I. OBJECTIVE: To compare the
      variability of patterns of depressive symptoms between two consecutive depressive
      episodes in patients with bipolar disorder type I. METHODS: Review of
      prospectively collected data from 136 subjects of an out-patient bipolar unit
      from 1997 to 2007. Binomial statistics was used for the analysis of Hamilton
      Depression Rating Scale (HDRS)-31 items of the first and second episodes, and the
      correlation of the HDRS-31 item scores of both episodes was determined using the
      Spearman coefficient. RESULTS: Ten depressive symptoms showed a significant
      correlation between index and subsequent episodes: psychological anxiety, somatic
      anxiety, somatic symptoms, diurnal variation, paranoid symptoms, obsessive and
      compulsive symptoms, hypersomnia, loss of appetite and helplessness. Only four
      symptoms were stable in both statistical tests: paranoid symptoms, obsessive
      compulsive symptoms, loss of appetite and hypersomnia. CONCLUSIONS: Paranoid and
      obsessive-compulsive symptoms, loss of appetite and hypersomnia tended to be
      found in successive episodes. However, the moderate correlations of the symptoms
      across two depressive recurrences suggested that clinical presentations in
      bipolar depression may not be predicted by symptom profiles presented in previous
      episodes.

PMID- 25385215
TI  - Prematurity and low birth weight as risk factors for the development of affective
      disorder, especially depression and schizophrenia: a register study.
AB  - Larsen JK, Bendsen BB, Foldager L, Munk-Jorgensen P. Prematurity and low birth
      weight as risk factors for the development of affective disorder, especially
      depression and schizophrenia: a register study. BACKGROUND: The present study
      examined whether low birth weight, prematurity or low birth weight adjusted for
      gestational age are risk factors for the subsequent development of affective
      disorder, especially depression. METHODS: A population-based case-control design
      was applied to the Danish Medical Birth Register and the Danish Psychiatric
      Central Register to identify all individuals born between 1 January 1974 and 31
      December 1990 and diagnosed prior to 29 August 2003 with affective disorder alone
      (ICD-10 F3; 4297 females, 1861 males), schizophrenia alone (ICD-10 F2; 1364
      females, 2292 males) or both disorders (ICD-10 F3 + F2; 450 females, 405 males).
      The association between low birth weight and the risk of developing affective
      disorder and/or schizophrenia was analysed by conditional logistic regression
      analysis. RESULTS: Low birth weight was found to be associated with a
      significantly elevated risk of developing schizophrenia alone (p = 0.021) and
      both affective disorder and schizophrenia (p = 0.024), and a non-significantly
      elevated risk of developing affective disorder alone (p = 0.063). The effect
      remained significant in the affective disorder and schizophrenia groups (p =
      0.039) when correcting for gestational age (premature birth), but was lost in the
      group with both disorders. Premature birth per se was found to be associated with
      a significantly elevated risk of developing both affective disorder and
      schizophrenia (p = 0.00018), an effect that remained significant after adjustment
      for low birth weight. CONCLUSION: Prematurity and low birth weight were found to
      be risk factors for subsequent development of affective disorder (especially
      depression) and schizophrenia.

PMID- 25385216
TI  - Effect of chronic administration of ketamine on the mitochondrial respiratory
      chain activity caused by chronic mild stress.
AB  - Rezin GT, Goncalves CL, Daufenbach JF, Carvalho-Silva M, Borges LS, Vieira JS,
      Hermani FV, Comim CM, Quevedo J, Streck EL. Effect of chronic administration of
      ketamine on the mitochondrial respiratory chain activity caused by chronic mild
      stress. OBJECTIVE: Recently, we reported that mitochondrial respiratory chain
      complexes I, III and IV were inhibited in the cerebral cortex and cerebellum of
      rats submitted to chronic mild stress (CMS) and that acute ketamine
      administration reversed this effect. Therefore, we investigated whether the
      inhibition of these enzymes may be reversed by chronic administration of
      ketamine. METHODS: Adult male Wistar rats were submitted to CMS and chronically
      treated with ketamine. After 40 days of CMS, consumption of sweet food, adrenal
      gland weight, body weight and enzymatic activity of the complexes were measured.
      RESULTS: We verified that CMS decreased the intake of sweet food, increased the
      adrenal gland weight and the control group gained weight after 40 days but the
      stressed group did not; ketamine administration reversed these effects. We also
      verified that chronic administration of ketamine reversed the inhibition of
      complexes I, III and IV in cerebral cortex. However, in cerebellum, only complex
      IV inhibition was reversed. The chronic ketamine administration partially
      reverses the inhibition caused by CMS. CONCLUSION: We hypothesise that CMS
      inhibits complexes I, III and IV activities and that chronic administration of
      ketamine administration partially reverses such an effect. Therefore, it seems
      reasonable to propose that ketamine administration might be a useful therapy for
      patients affected by major depression.

PMID- 25385217
TI  - An efficient nanoscale heterogeneous catalyst for the capture and conversion of
      carbon dioxide at ambient pressure.
AB  - Silver nanoparticles were successfully supported on the zeolite-type metal
      organic framework MIL-101 to yield Ag@MIL-101 by a simple liquid impregnation
      method. For the first time, the conversion of terminal alkynes into propiolic
      acids with CO2 was achieved by the use of the Ag@MIL-101 catalysts. Owing to the
      excellent catalytic activity, the reaction proceeded at atmospheric pressure and
      low temperature (50  degrees C). The Ag@MIL-101 porous material is of outstanding
      bifunctional character as it is capable of simultaneously capturing and
      converting CO2 with low energy consumption and can be recovered easily by
      centrifugation. 

PMID- 25385218
TI  - Cholesteatoma and meningoencephalitis in a dog with chronic otitis externa.
AB  - A 10-year-old female spayed German Shepherd dog, with a year-long history of
      recurrent left ear infections, was presented for progressive ataxia, head tilt,
      and pain on opening of the mouth. On physical examination, a large amount of
      ceruminous debris was present in the left ear and multiple neurologic defects
      localizing to the cerebellum and vestibular system were identified. Magnetic
      resonance imaging (MRI) demonstrated a minimally contrast-enhancing mass within
      the left bulla, an intracranial space-occupying, heterogeneously contrast
      enhancing lesion at the level of the left cerebello-medullary junction, and
      contrast enhancement of the ipsilateral meninges. Cerebrospinal fluid analysis
      revealed a marked mixed cell pleocytosis (nucleated cell count 655 cells/MUL).
      The mass was visualized within the horizontal ear canal by otoscopic examination
      and a biopsy was taken. Impression smears of the biopsy contained many anucleate
      keratinized squamous epithelial cells, mild mixed inflammation, and few
      presumptive fibroblasts. With the provided clinical history and MRI findings, a
      cytologic diagnosis of cholesteatoma was made. A ventral bulla osteotomy was
      performed, and histopathologic examination of resected tissue confirmed the
      cytologic diagnosis of cholesteatoma. The dog's clinical symptoms improved
      postoperatively, but the dog died of unrelated causes, 3.5 months later. To our
      knowledge, this is the first description of the cytologic features of a
      cholesteatoma, which is a nonneoplastic, but locally invasive epidermoid cyst, in
      the middle ear of dogs. 

PMID- 25385219
TI  - Interdisciplinary expert consensus on management of type B intramural haematoma
      and penetrating aortic ulcer.
AB  - An expert panel on the treatment of type B intramural haematoma (IMH) and
      penetrating atherosclerotic ulcer (PAU) consisting of cardiologists,
      cardiothoracic surgeons, vascular surgeons and interventional radiologists
      reviewed the literature to develop treatment algorithms using a consensus method.
      Data from 46 studies considered relevant were retrieved for a total of 1386
      patients consisting of 925 with IMH, and 461 with PAU. The weighted mean 30-day
      mortality from IMH was 3.9%, 3-year aortic event-related mortality with medical
      treatment 5.4%, open surgery 23.2% and endovascular therapy 7.1%. In patients
      with PAU early and 3-year aortic event-mortality rates with open surgery were
      15.9 and 25.0%, respectively, and with TEVAR were 7.2 and 10.4%, respectively.
      According to panel consensus statements, haemodynamic instability, persistent
      pain, signs of impending rupture and progressive periaortic haemorrhage in two
      successive imaging studies require immediate surgical or endovascular treatment.
      In the absence of these complications, medical treatment is warranted, with
      imaging control at 7 days, 3 and 6 months and annually thereafter. In the chronic
      phase, aortic diameter >55 mm or a yearly increase >= 5 mm should be considered
      indications for open surgery or thoracic endovascular treatment, with the latter
      being preferred. In complicated type B aortic PAU and IMH, endovascular repair is
      the best treatment option in the presence of suitable anatomy.

PMID- 25385220
TI  - Re: development of a next-generation tissue valve using a glutaraldehyde-fixed
      porcine aortic valve treated with decellularization, alpha-galactosidase, space
      filler, organic solvent and detoxification.

PMID- 25385221
TI  - Endovascular treatment of a tuberculous aneurysm of the descending thoracic aorta
      in a young patient.

PMID- 25385222
TI  - Molecular signaling of the HMGB1/RAGE axis contributes to cholesteatoma
      pathogenesis.
AB  - Cholesteatoma represents progressive expansion of the keratinizing squamous
      epithelium in the middle ear with subsequent chronic inflammation in
      subepithelial connective tissues. The hypothesis was tested that receptor for
      advanced glycation endproduct (RAGE) and its ligand, high-mobility box 1 (HMGB1),
      are overexpressed in cholesteatoma, and the RAGE/HMGB1 axis might contribute to
      its pathogenesis. Cholesteatoma samples (n = 36) and 27 normal skin specimens
      were studied by immunohistochemistry (IHC) for HMGB1 and RAGE expression. Effects
      of HMGB1 signaling on proliferation, migration, cytokine production, and
      apoptosis of human immortalized keratinocytes (HaCaTs) and normal keratinocytes
      were studied by quantitative reverse transcription (qRT)-PCR, IHC, Western blots,
      and flow cytometry after cell co-incubation with HMGB1. While all studied tissues
      expressed HMGB1, its expression was higher in cholesteatoma than in normal skin
      (p < 0.0001). All cases of cholesteatoma also showed elevated RAGE expression
      levels, and only 7/27 (26 %) of normal skin specimens were weakly positive for
      RAGE. Proliferation and migration of HaCaT cells incubated with HMGB1 were up
      regulated (p < 0.05). HMGB1 also prevented HaCaT cell apoptosis and induced
      activation of several molecular signaling pathways in keratinocytes. The data
      suggest that in cholesteatoma, HMGB1 released from stressed or necrotic
      epithelial cells and binding to RAGE overexpressed in keratinocytes initiates
      molecular signaling that culminates in pro-inflammatory cytokine release and
      chronic inflammation. KEY MESSAGE: HMGB1 signaling engages multiple activation
      pathways in RAGE-positive keratinocytes. HMGB1 protects RAGE-positive
      keratinocytes from drug-induced apoptosis. Keratinocyte proliferation is
      controlled via RAGE and HMGB1 molecular signaling. Molecular signaling of the
      HMGB1/RAGE axis contributes to cholesteatoma pathogenesis.

PMID- 25385228
TI  - NAFLD: Ketogenesis could be a determinant of steatohepatitis.

PMID- 25385227
TI  - Mycobiota in gastrointestinal diseases.
AB  - New insights gained through the use of state-of-the-art technologies, including
      next-generation sequencing, are starting to reveal that the association between
      the gastrointestinal tract and the resident mycobiota (fungal community) is
      complex and multifaceted, in which fungi are active participants influencing
      health and disease. Characterizing the human mycobiome (the fungi and their
      genome) in healthy individuals showed that the gastrointestinal tract contains 66
      fungal genera and 184 fungal species, with Candida as the dominant fungal genera.
      Although fungi have been associated with a number of gastrointestinal diseases,
      characterization of the mycobiome has mainly been focused on patients with IBD
      and graft-versus-host disease. In this Review, we summarize the findings from
      studies investigating the relationship between the gut mycobiota and
      gastrointestinal diseases, which indicate that fungi contribute to the
      aggravation of the inflammatory response, leading to increased disease severity.
      A model explaining the mechanisms underlying the role of the mycobiota in
      gastrointestinal diseases is also presented. Our understanding of the
      contribution of the mycobiota to health and disease is still in its infancy and
      leaves a number of questions to be addressed. Answering these questions might
      lead to novel approaches to prevent and/or manage acute as well as chronic
      gastrointestinal disease. 

PMID- 25385229
TI  - Infection: microbiota reconstitution for resistance to Clostridium difficile
      infection--fight fire with fire?

PMID- 25385230
TI  - Rapid modulation of droplet composition with pincer microvalves.
AB  - Single-layer membrane valves are simple to fabricate and to integrate into
      microfluidic devices. However, due to their rectangular flow channel geometry,
      they do not fully seal. Here, we show that liquid flow can be reduced by over 3
      orders of magnitude, enabling the contents of forming droplets to be dynamically
      modulated. We use this precision control to perform combinatorial DNA synthesis
      in the droplets. 

PMID- 25385231
TI  - When Cri du chat syndrome meets Edwards syndrome.
AB  - It has been well established that the 5p deletion causes Cri du chat syndrome,
      typically characterized by a cat-like cry, and that duplication of 18q causes
      Edwards syndrome; the two are rare genetic abnormalities that separately lead to
      physical and mental impairments. However, the severity of the clinicopathological
      characteristics that arise when these two aberrations occur in one patient is
      unknown. Here, the first case in our knowledge of a single patient (a two-year
      old female) with 5p partial monosomy and 18q partial trisomy is described. In the
      present study, chromosome microarray analysis was performed, which identified the
      imbalance of chromosomes 5 and 18 in the patient. The chromosome aberrations were
      further confirmed by fluorescence in situ hybridization. By comparing the
      phenotypes of combined case with those of the individual syndromes, severe
      clinical phenotypes of the 5p (5p15.33-p13.3) deletion were confirmed, however,
      the net effect of the duplication of 18q22.3-q23 was not determined, as this
      duplication only appeared to have a weak effect on the patient's phenotypes. The
      correlation between these chromosomal aberrations and their clinical features has
      implications for the identification of critical regions of 5p and 18q,
      particularly for the functional mapping of chromosome 18.

PMID- 25385232
TI  - Reduction of metastatic and angiogenic potency of malignant cancer by Eupatorium
      fortunei via suppression of MMP-9 activity and VEGF production.
AB  - Eupatorium fortunei has long been used to treat nausea and poor appetite, and has
      been prescribed as a diuretic and detoxifying drug in Chinese medicine. Recent
      studies have demonstrated that E. fortunei possesses anti-bacterial, anti
      oxidant, and anti-diabetic activities, as well as cytotoxicity to human leukemia
      cells. However, at non-toxic concentrations, the effects of an aqueous extract of
      E. fortunei (WEF) on the metastatic and angiogenic potential of malignant tumor
      cells have not been reported. In this study, we found that WEF suppressed the
      metastatic properties, including anchorage-independent colony formation,
      migration, and invasion, by downregulating the proteolytic activity of MMP-9. NF
      kappaB activation and the phosphorylation of p38 and JNK were reduced
      significantly by WEF. Additionally, WEF inhibited tumor-induced angiogenesis
      markedly, affecting HUVEC migration, tube formation by HUVECs, and microvessel
      sprouting from rat aortic rings via a reduction in VEGF in tumors. In a pulmonary
      metastasis model, daily administration of WEF at 50 mg/kg markedly decreased
      metastatic colonies of intravenously injected B16F10 cells on the lung surface in
      C57BL/6J mice. Further, none of the WEF-administered mice exhibited systemic
      toxicity. Taken together, our results indicate that WEF is a potential
      therapeutic herbal product that may be useful for controlling malignant
      metastatic cancer.

PMID- 25385233
TI  - The alteration of protein prenylation induces cardiomyocyte hypertrophy through
      Rheb-mTORC1 signalling and leads to chronic heart failure.
AB  - G protein-regulated cell function is crucial for cardiomyocytes, and any
      deregulation of its gene expression or protein modification can lead to
      pathological cardiac hypertrophy. Herein, we report that protein prenylation, a
      lipidic modification of G proteins that facilitates their association with the
      cell membrane, might control the process of cardiomyocyte hypertrophy. We found
      that geranylgeranyl diphosphate synthase (GGPPS), a key enzyme involved in
      protein prenylation, played a critical role in postnatal heart growth by
      regulating cardiomyocyte size. Cardiac-specific knockout of GGPPS in mice led to
      spontaneous cardiac hypertrophy, beginning from week 4, accompanied by the
      persistent enlargement of cardiomyocytes. This hypertrophic effect occurred by
      altered prenylation of G proteins. Evaluation of the prenylation, membrane
      association and hydrophobicity showed that Rheb was hyperactivated and increased
      mTORC1 signalling pathway after GGPPS deletion. Protein farnesylation or mTORC1
      inhibition blocked GGPPS knockdown-induced mTORC1 activation and suppressed the
      larger neonatal rat ventricle myocyte size and cardiomyocyte hypertrophy in vivo,
      demonstrating a central role of the FPP-Rheb-mTORC1 axis for GGPPS deficiency
      induced cardiomyocyte hypertrophy. The sustained cardiomyocyte hypertrophy
      progressively provoked cardiac decompensation and dysfunction, ultimately causing
      heart failure and adult death. Importantly, GGPPS was down-regulated in the
      hypertrophic hearts of mice subjected to transverse aortic constriction (TAC) and
      in failing human hearts. Moreover, HPLC-MS/MS detection revealed that the
      myocardial farnesyl diphosphate (FPP):geranylgeranyl diphosphate (GGPP) ratio was
      enhanced after pressure overload. Our observations conclude that the alteration
      of protein prenylation promotes cardiomyocyte hypertrophic growth, which acts as
      a potential cause for pathogenesis of heart failure and may provide a new
      molecular target for hypertrophic heart disease clinical therapy.

PMID- 25385234
TI  - Development and validation of a liquid chromatography with mass spectrometry
      method to determine resveratrol and piceid isomers in beeswax.
AB  - This paper represents the first report of a liquid chromatography coupled to
      electrospray ionization mass spectrometry method for simultaneously analyzing
      resveratrol and piceid isomers (cis and trans) in beeswax. An efficient
      extraction procedure has been proposed (average analyte recoveries were between
      89 and 95%); this involved a solid-liquid extraction using a mixture of ethanol
      and water (80:20, v/v) and a concentration step in a rotary evaporator. The
      separation of all the compounds was achieved using a C18 column and a mobile
      phase composed of ammonium formate 0.03 M in water and acetonitrile in gradient
      elution mode at a flow rate of 1 mL/min. The method was fully validated in terms
      of selectivity, limits of detection and quantification, linearity, precision, and
      accuracy. The limits of detection and quantification ranged from 1.0 to 1.7 and
      3.5 to 5.5 MUg/kg, respectively. Finally, the proposed method was applied to
      analyze beeswax samples collected from experimental and organic apiaries.

PMID- 25385239
TI  - Telbivudine is associated with improvement of renal function in patients
      transplanted for HBV liver disease.
AB  - Recent studies showed that telbivudine in patients with hepatitis B virus (HBV)
      infection improved their glomerular filtration rate (GFR), but data regarding its
      impact on renal function in liver transplant (LT) recipients are very limited. We
      evaluated 17 consecutive recipients who received at baseline nucleos(t)ide
      analogue(s) (NAs) other than telbivudine for 12 months, and then they were
      switched to telbivudine prophylaxis for another 12 months. In each patient,
      laboratory data including evaluation of GFR (using MDRD and CKD-EPI) were
      prospectively recorded. The changes in GFR (DeltaGFR) between baseline and after
      12 months (1st period) and between telbivudine initiation and 24 months (2nd
      period) were evaluated. All patients remained serum HBsAg and HBV-DNA negative.
      GFR-MDRD at baseline, 12 months and 24 months were 72 +/- 18, 67.8 +/- 16 and
      70.3 +/- 12 mL/min, respectively, (P = 0.025 for comparison between 12 months and
      24 months). DeltaGFR at the 1st period was significantly lower, compared with
      DeltaGFR at the 2nd period [mean DeltaGFR-MDRD: -4.2 (range: -24-9) vs 2.5
      (range: -7-22) mL/min, P = 0.013; mean DeltaGFR-CKD-EPI: -4.2 (range: -19-10) vs
      4.0 (range: -7-23) mL/min, P = 0.004], although the serum levels of calcineurin
      inhibitors were similar between the two periods. A second group of recipients (n
      = 17) who remained under the same nontelbivudine NA(s) for 24 months had a
      decline in the mean eGFR during the total follow-up period. In conclusion, we
      showed that telbivudine administration in LT recipients for HBV cirrhosis was
      effective and it was associated with significant improvement in renal function,
      but this remains to be confirmed in larger well-designed studies.

PMID- 25385240
TI  - Outcomes of adjuvant endocrine therapy and hormone receptor status change
      following neoadjuvant chemotherapy in breast cancer patients.
AB  - BACKGROUND: This retrospective study investigated the therapeutic benefit of
      adjuvant endocrine therapy (ET) in breast cancer patients with hormone receptor
      (HR) status change from positive to negative after neoadjuvant chemotherapy
      (NAC). METHODS: From December 2000 to November 2010, 97 eligible patients with a
      positive-to-negative switch of HR status after NAC were identified. All patients
      were categorized into 2 groups on the basis of the administration of ET: 57 ET
      administered patients and 40 ET-naive patients. Survival analyses were performed
      to examine the prognostic value of ET administration as well as other clinical
      and pathologic variables. RESULTS: The administration of ET was significantly
      associated with improved disease-free survival (p=0.018) in patients with a
      positive-to-negative switch of HR status. The 5-year disease-free survival rates
      were 77.0% and 55.5%, respectively, in ET-administered patients and ET-naive
      patients. The 5-year overall survival rate for ET-administered patients was also
      higher than that of ET-naive patients (81.3% vs. 72.7%, p=0.053), albeit this was
      statistically insignificant. CONCLUSIONS: This study revealed that patients with
      HR altered from positive to negative after NAC still benefit from ET. The HR
      status should be evaluated not only in specimens obtained during post-NAC surgery
      but also in specimens biopsied before NAC.

PMID- 25385241
TI  - Genetic diversity of CYP3A4 and CYP3A5 polymorphisms in North African populations
      from Morocco and Tunisia.
AB  - The genes CYP3A4 and CYP3A5 form part of a cluster of cytochrome P450 genes
      involved in drug metabolism reactions. The allelic variants of these genes
      CYP3A4*1B, CYP3A4*3, CYP3A4*17 and CYP3A5*3 have been linked both to the reduced
      catalytic activity of cytochromes and to prostate cancer risk in whites, though
      scarce data exist for North African populations. The main objective of this study
      was to describe CYP3A4*3, CYP3A4*17, CYP3A4*1B and CYP3A5*3 allele frequencies
      and haplotype variation in Moroccan Berbers and the general Tunisian population.
      The data obtained for the Tunisian participants were consistent with the European
      allele frequency ranges described, while Moroccan Berbers showed high frequencies
      of CYP3A4*17 (1.8%), CYP3A4*3 (8.5%) and the CYP3A4*1B/CYP3A5*3 haplotype
      (18.4%). This haplotype, linked to an increased risk of prostate cancer, was
      detected at a much higher frequency compared with the present Tunisian population
      (8.4%) or with reported frequencies for populations such as whites (0.6%) or
      African Americans (5.3%). 

PMID- 25385242
TI  - Case report: postradiation chondrosarcoma with a short latency period of 6
      months.
AB  - We describe a case of postradiation chondrosarcoma after basal cell carcinoma
      treatment. At the time he presented, the patient was a 35-year-old man who had
      received radiotherapy at a dose of 70 Gy for 8 weeks. Six months after radiation
      treatment, a rapidly growing mass at the upper right alveolar ridge of the gums,
      where radiation had been given, was diagnosed as chondrosarcoma. Generally,
      chondrosarcoma occurs after a latency period of several years following
      radiation. However, there are a few relevant reports indicating that
      maxillofacial chondrosarcoma can develop after radiotherapy for basal cell
      carcinoma, with a short latency of 6 months. We hypothesize that the dosage and
      treatment time of radiation may have played a role in the opening/closing of the
      Hh-signaling pathway in the case of this patient. 

PMID- 25385243
TI  - Molecular characterization of Cryptosporidium spp. in pre-weaned calves in
      Shaanxi Province, north-western China.
AB  - Cryptosporidium, a worldwide protozoan parasite, is one of the most common causes
      of diarrhoea in humans and animals. The aim of the present study was to determine
      Cryptosporidium species/genotypes in pre-weaned calves in Shaanxi Province using
      PCR and sequencing based on the small subunit rRNA gene. A total of 258 faecal
      samples were collected from pre-weaned calves in 19 different farms from six
      areas in Shaanxi Province, north-western China. Cryptosporidium infection was
      detected in 14 of 19 farms (73.7 %), with a total prevalence of 20.2 % (52/258).
      Both dairy and Qinchuan (beef) cattle were found with Cryptosporidium infection.
      Three Cryptosporidium species, namely Cryptosporidium bovis (n = 26),
      Cryptosporidium andersoni (n = 14) and Cryptosporidium ryanae (n = 12), were
      detected in pre-weaned calves in Shaanxi Province, with C. bovis (in 12 farms)
      identified as the most common species on cattle farms. Two additional and
      previously unknown C. ryanae genotypes, CRTypes III and IV, were observed in the
      present study. However, the zoonotic species, Cryptosporidium parvum, was not
      detected in this study, which suggested a low zoonotic potential in
      Cryptosporidium-infected pre-weaned calves in this province. 

PMID- 25385244
TI  - Comparing sound localization deficits in bilateral cochlear-implant users and
      vocoder simulations with normal-hearing listeners.
AB  - Bilateral cochlear-implant (BiCI) users are less accurate at localizing free
      field (FF) sound sources than normal-hearing (NH) listeners. This performance gap
      is not well understood but is likely due to a combination of compromises in
      acoustic signal representation by the two independent speech processors and
      neural degradation of auditory pathways associated with a patient's hearing loss.
      To exclusively investigate the effect of CI speech encoding on horizontal-plane
      sound localization, the present study measured sound localization performance in
      NH subjects listening to vocoder processed and nonvocoded virtual acoustic space
      (VAS) stimuli. Various aspects of BiCI stimulation such as independently
      functioning devices, variable across-ear channel selection, and pulsatile
      stimulation were simulated using uncorrelated noise (Nu), correlated noise (N0),
      or Gaussian-enveloped tone (GET) carriers during vocoder processing.
      Additionally, FF sound localization in BiCI users was measured in the same
      testing environment for comparison. Distinct response patterns across azimuthal
      locations were evident for both listener groups and were analyzed using a
      multilevel regression analysis. Simulated implant speech encoding, regardless of
      carrier, was detrimental to NH localization and the GET vocoder best simulated
      BiCI FF performance in NH listeners. Overall, the detrimental effect of vocoder
      processing on NH performance suggests that sound localization deficits may
      persist even for BiCI patients who have minimal neural degradation associated
      with their hearing loss and indicates that CI speech encoding plays a significant
      role in the sound localization deficits experienced by BiCI users. 

PMID- 25385245
TI  - Growth Restriction in Infants and Young Children with Congenital Heart Disease.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of growth
      restriction in infants and young children with congenital heart disease (CHD) and
      investigate the relationship between poor growth, feeding difficulties, cardiac
      classification, and nutrition intervention on outcomes. DESIGN: This is a
      prospective observational cohort study of infants and young children with CHD
      aged 0-3 years admitted to hospital for cardiac surgery. Anthropometry, growth
      history, cardiac classification, cardiac diagnosis, feeding difficulty, and
      nutrition intervention data were collected for 78 participants. RESULTS: Many
      participants demonstrated growth restriction as evidenced by a z-score <= -2 for
      population growth parameters including weight/age z-score (n = 18, 23%),
      height/age z-score (n = 16, 21%), and weight/height z-score (n = 12, 18%).
      Increased hospital length of stay was associated with factors including faltering
      growth preadmission (P = .009), tube feeding required preadmission (P = .002),
      diagnosis of cyanotic CHD (P = .015), and presence of a feeding difficulty (P =
      .015). CONCLUSIONS: Growth restriction remains an ongoing problem in children
      with CHD. Faltering growth preadmission and lower growth parameters were
      associated with an increased hospital length of stay. Nutritional screening from
      diagnosis may detect growth faltering, improve access to early nutrition
      intervention, and improve patient outcomes.

PMID- 25385246
TI  - Management of Pentalogy of Cantrell with complete ectopia cordis and Double
      Outlet Right Ventricle.
AB  - Pentalogy of Cantrell (PoC) is a rare congenital midline defect. We present a
      case and its treatment of PoC with complete ectopia cordis and congenital heart
      disease. Postnatally the congenital heart defect was surgically corrected and the
      ectopic heart was covered by musculous mobilized flap. Due to cephalic
      orientation of the heart and limited intrathoracic space, replacement of the
      heart into the thoracic cavity was initially not performed. After 11 years of
      follow up our patient now is without relevant limitations solely wearing a
      thoracic shelter. This case elucidates the complexity of further management. The
      potential risk of disastrous hemodynamic compromise by intrathoracic shift is to
      compare with the limited safety of the ectopic heart. 

PMID- 25385247
TI  - Antimony(III) and bismuth(III) amides containing pendant N-donor groups--a
      combined experimental and theoretical study.
AB  - N,N- and N,N,N-chelated antimony(III) and bismuth(III) chlorides L(1-3)MCl2 1-4
      [for L(1): M = Sb (1), for L(2): M = Sb (2) and for L(3): M = Sb (3) and Bi (4)],
      containing ligands L(1-3) derived from the pyrrole ring (where L(1) = C4H3N-2
      (CH[double bond, length as m-dash]N-2',6'-iPr2C6H3), L(2) = C4H2N-2,5-(CH2NMe2)2,
      L(3) = C4H2N-2,5-(CH2NC4H8)2), were prepared by the treatment of lithium
      precursors with SbCl3 or BiCl3. Molecular structures 1-4 of were described both
      in solution (NMR spectroscopy) and in the solid state (single-crystal X-ray
      diffraction analysis). Structures of 1-4 were also subjected to a density
      functional theory study.

PMID- 25385248
TI  - An uncommon long-term survival case of primary cardiac leiomyosarcoma.
AB  - Primary cardiac sarcoma is a rare aggressive entity. It constitutes the second
      most common type of primary cardiac neoplasms. Its management has largely been
      guided by small retrospective series with a median survival of 6 months. Here, we
      discuss a unique case of 8-year survival cardiac leiomyosarcoma managed by
      surgical and adjuvant therapy. 

PMID- 25385249
TI  - GP bashing not the answer to antibiotic overprescribing, professor tells summit.

PMID- 25385251
TI  - Assessing animal welfare in sow herds using data on meat inspection, medication
      and mortality.
AB  - This paper aims to contribute to the development of a cost-effective alternative
      to expensive on-farm animal-based welfare assessment systems. The objective of
      the study was to design an animal welfare index based on central database
      information (DBWI), and to validate it against an animal welfare index based on
      farm animal-based measurements (AWI). Data on 63 Danish sow herds with herd-sizes
      of 80 to 2500 sows and an average herd size of 501 were collected from three
      central databases containing: Meat inspection data collected at animal level in
      the abattoir, mortality data at herd level from the rendering plants of DAKA, and
      medicine records at both herd and animal group level (sow with piglets, weaners
      or finishers) from the central database Vetstat. Selected measurements taken from
      these central databases were used to construct the DBWI. The relative welfare
      impacts of both individual database measurements and the databases overall were
      assigned in consultation with a panel consisting of 12 experts. The experts were
      drawn from production advisory activities, animal science and in one case an
      animal welfare organization. The expert panel weighted each measurement on a
      scale from 1 (not-important) to 5 (very important). The experts also gave
      opinions on the relative weightings of measurements for each of the three
      databases by stating a relative weight of each database in the DBWI. On the basis
      of this, the aggregated DBWI was normalized. The aggregation of AWI was based on
      weighted summary of herd prevalence's of 20 clinical and behavioural measurements
      originating from a 1 day data collection. AWI did not show linear dependency of
      DBWI. This suggests that DBWI is not suited to replace an animal welfare index
      using on-farm animal-based measurements.

PMID- 25385250
TI  - Unemployment is associated with high cardiovascular event rate and increased all
      cause mortality in middle-aged socially privileged individuals.
AB  - PURPOSE: To assess prospectively the association between employment status and
      cardiovascular health outcomes in socially privileged individuals. METHODS: The
      incidence of fatal and non-fatal cardiovascular events and all-cause mortality
      rate were monitored during 12 years in a national sample of 5,852 French
      volunteers, aged 45-64 years, who were free of cardiovascular disease or other
      overt disease at baseline. The association between health outcomes and employment
      status was tested using Cox proportional modelling with adjustment for
      confounding factors. RESULTS: Compared to randomly selected individuals, these
      volunteers were characterized by higher education level and socio-economic status
      and lower cardiovascular risk and mortality rate. A total of 242 cardiovascular
      events (3.5 events per 1,000 person-years) and 152 deaths from all causes (2.2
      deaths per 1,000 person-years) occurred during follow-up. After adjustment for
      age and gender, both cardiovascular event risk [HR (95% CI) 1.84 (1.15-2.83), p =
      0.01] and all-cause mortality [2.79 (1.66-4.47), p = 0.0002] were increased in
      unemployed individuals compared to workers. These poor health outcomes were
      observed to the same extent after further adjustment for clinical, behavioural
      and socio-demographic characteristics of individuals at baseline [HR (95% CI)
      1.74 (1.07-2.72), p = 0.03 and 2.89 (1.70-4.69), p = 0.0002, respectively]. In
      contrast, neither cardiovascular event risk nor all-cause mortality was
      significantly increased in retired individuals compared to workers after
      adjustment for confounding factors. CONCLUSIONS: These results support the
      existence of a link between unemployment and poor cardiovascular health and
      suggest that this link is not mediated by conventional risk factors in middle
      aged socially privileged individuals.

PMID- 25385252
TI  - AdipoQ T45 G and G276 T Polymorphisms and Susceptibility to Nonalcoholic Fatty
      Liver Disease Among Asian Populations: A Meta-Analysis and Meta-Regression.
AB  - BACKGROUND: Adiponectin (AdipoQ) is an adipose-derived plasma protein that plays
      an important role in hepatic lipoprotein-lipid metabolism. Emerging evidence have
      shown that two common polymorphisms (T45 G and G276 T) in the AdipoQ gene may
      contribute to increasing susceptibility to nonalcoholic fatty liver disease
      (NAFLD); however individually published studies show inconclusive results. This
      meta-analysis aimed to derive a more precise estimation of the association of
      AdipoQ T45 G (rs2241766 T>G) and G276 T (rs1501299 G>T) polymorphisms with NAFLD
      risk. METHOD: Potential relevant studies were identified covering the following
      databases: PubMed, Embase, Web of Science, the Cochrane Library, Chinese National
      Knowledge Infrastructure (CNKI), Chinese Bio-medicine Database (CBM), and Chinese
      Sci-tech Journals databases. Statistical analyses were calculated using the
      version 12.0 STATA software (Stata Corp, College Station, TX, USA). Odds ratios
      (ORs) and its corresponding 95% confidence interval (CI) were calculated. RESULT:
      Ten case-control studies were included with a total of 2,672 subjects, of these
      1,117 being NAFLD patients and 1,555 being healthy controls. Our meta-analysis
      results revealed that the T variant of AdipoQ rs2241766 T>G polymorphism may be
      associated with an increased risk of NAFLD. There was also a significant
      association between the G variant of AdipoQ rs1501299 G>T polymorphism and an
      increased risk of NAFLD. Country-stratified analysis indicated that a higher
      AdipoQ rs2241766 T>G polymorphism was closely related with an increased risk of
      NAFLD in Chinese and Indian populations (all Ps < 0.05); a similar result was
      observed in Chinese populations between AdipoQ rs2241766 T>G polymorphism and an
      increased risk of NAFLD (P < 0.05). CONCLUSION: In conclusion, the current meta
      analysis indicates that AdipoQ rs2241766 T>G and rs1501299 G>T polymorphisms may
      contribute to an increasing susceptibility to NAFLD. Moreover, this meta-analysis
      also suggests for future larger studies with stratified case-control population,
      and greater focus on the gene-environment interactions regarding NAFLD
      susceptibility for valid studies.

PMID- 25385253
TI  - Admission privileges and clinical responsibilities for interventional
      radiologists.
AB  - Although clinical involvement by interventional radiologists in the care of their
      patients was advocated at the inception of the specialty, the change into the
      clinical paradigm has been slow and patchy for reasons related to pattern of
      practice, financial remuneration or absence of training. The case for the value
      of clinical responsibilities has been made in a number of publications and the
      consequences of not doing so have been manifest in the erosion of the role of the
      interventional radiologists particularly in the fields of peripheral vascular and
      neuro intervention. With the recent recognition of interventional radiology (IR)
      as a primary specialty in the USA and the formation of IR division in the Union
      of European Medical Specialists and subsequent recognition of the subspecialty in
      many European countries, it is appropriate to relook at the issue and emphasize
      the need for measures to promote the clinical role of the interventional
      radiologist. 

PMID- 25385254
TI  - Stenting of the Cystic Duct in Benign Disease: A Definitive Treatment for the
      Elderly and Unwell.
AB  - PURPOSE: There have been few case reports describing cystic duct stent insertion
      in the management of acute cholecystitis secondary to benign disease with no case
      series published to date. We present our series demonstrating the role of cystic
      duct stents in managing benign gallbladder disease in those patients unfit for
      surgery. MATERIALS AND METHODS: Thirty three patients unfit for surgery in our
      institution underwent cystic duct stent insertion for the management of acute
      cholecystitis in the period June 2008 to June 2013. Patients underwent a mixture
      of transperitoneal and transhepatic gallbladder puncture. The cystic duct was
      cannulated with a hydrophilic guidewire which was subsequently passed through the
      common bile duct and into the duodenum. An 8Fr 12-cm double-pigtail stent was
      placed with the distal end lying within the duodenum and the proximal end within
      the gallbladder. RESULTS: Ten patients presented with gallbladder perforation, 21
      patients with acute cholecystitis, 1 with acute cholangitis and 1 with
      necrotising pancreatitis. The technical success rate was 91%. We experienced a
      13% complication rate with 3% mortality rate at 30 days. CONCLUSION: Cystic duct
      stent insertion can be successfully used to manage acute cholecystitis,
      gallbladder empyema or gallbladder perforations in those unfit for surgery and
      should be considered alongside external gallbladder drainage as a definitive mid
      term treatment option.

PMID- 25385255
TI  - Neutrophils in atherosclerosis. A brief overview.
AB  - Atherosclerosis is a chronic inflammation of the arterial wall and the continuous
      infiltration of leukocytes into the plaque enhances the progression of the
      lesion. Because of the scarce detection of neutrophils in atherosclerotic plaques
      compared to other immune cells, their contribution was largely neglected.
      However, in the last years studies have accumulated pointing towards the
      contribution of neutrophils to atherogenesis. In addition, studies are emerging
      implying a role for neutrophils in advanced atherosclerosis and/or plaque
      destabilization. Thus, this brief review delivers an overview of the role of
      neutrophils during early and late stage atherosclerosis.

PMID- 25385256
TI  - Plasmon-enhanced fluorescence of PbS quantum dots for remote near-infrared
      imaging.
AB  - Gold nanoparticles with nanoscale protrusions can be synthesized by seed-mediated
      growth in favor of tuning the surface plasmon band towards the near-infrared
      regime. Electromagnetic field enhancement makes significant contribution to
      improve fluorescence emission of PbS quantum dots in the near-infrared window,
      identifying their application in remote imaging by collecting the scattered
      fluorescence of their hybrids. 

PMID- 25385257
TI  - Complications of decorative tattoos: recognition and management.
AB  - Tattooing is an ancient practice that enjoys continued popularity. Although a
      modern, professionally performed tattoo is generally safe, complications can
      occur. A skin biopsy of all tattoo reactions is recommended as some tattoo
      reactions have systemic implications. Tattoo-related infections are seen days to
      decades after tattooing, and range from acute pyogenic infections to cutaneous
      tuberculosis. In particular, non-tuberculous mycobacterial infections happen in
      tattoos with increasing frequency and are introduced at the time of tattooing
      through contaminated ink or water used to dilute inks. Despite a transition in
      tattoo pigments from metal salts to industrial azo dyes, hypersensitivity
      reactions also persist, and include eczematous, granulomatous, lichenoid, and
      pseudoepitheliomatous patterns (among others). Granulomatous tattoo reactions can
      be a clue to cutaneous or systemic sarcoidosis, particularly in the setting of
      interferon use. Pseudoepitheliomatous tattoo reactions have substantial overlap
      with squamous cell carcinoma and keratoacanthoma, making diagnosis and management
      difficult. Other malignancies and their benign mimics can occur in tattoos,
      raising questions about the safety of tattoo ink and its role in carcinogenesis. 

PMID- 25385258
TI  - The ApoE gene is related with exceptional longevity: a systematic review and meta
      analysis.
AB  - The objective of this meta-analysis was to determine the association of the
      apolipoprotein E (ApoE) gene with exceptional longevity (EL) (i.e., reaching 100+
      years) by identifying possible unequal distribution of alleles/genotypes in the
      common variants epsilon2, epsilon3, and epsilon4 among centenarians and younger
      population. The association of ApoE with EL was analyzed in a total of 2776
      centenarians (cases) and 11,941 younger controls (from 13 case-control studies)
      using the chi-squared test with the Yates correction. We conducted combined and
      separate analyses for all ethnic groups studied in the literature (Caucasian and
      Asian). The main result for all ethnic groups combined was that the likelihood of
      reaching EL was negatively associated with epsilon4 allele carriage [pooled odds
      ratio (OR)=0.43; 95% confidence interval (CI) 0.36, 0.50; p<0.001] and with
      epsilon4/epsilon4 (OR=0.18; 95% CI 0.08, 0.39; p<0.001), epsilon3/epsilon4
      (OR=0.44; 95% CI 0.37, 0.53; p<0.001) and epsilon2/epsilon4 genotypes (OR=0.48;
      95% CI 0.31, 0.74; p<0.001). In contrast, the epsilon2/epsilon3 genotype was
      positively associated with EL (OR=1.35; 95% CI 1.06, 1.72; p=0.017). When
      compared with the epsilon3 allele, the epsilon2 allele was not associated with
      increased odds of EL (OR=1.08; 95% CI 0.77, 1.50, p=0.660). The present meta
      analysis confirms that, besides its previously documented influence on
      Alzheimer's and cardiovascular disease risk, the ApoE gene is associated with the
      likelihood of reaching EL. 

PMID- 25385259
TI  - Following the digestion of milk proteins from mother to baby.
AB  - Little is known about the digestive process in infants. In particular, the
      chronological activity of enzymes across the course of digestion in the infant
      remains largely unknown. To create a temporal picture of how milk proteins are
      digested, enzyme activity was compared between intact human milk samples from
      three mothers and the gastric samples from each of their 4-12 day postpartum
      infants, 2 h after breast milk ingestion. The activities of 7 distinct enzymes
      are predicted in the infant stomach based on their observed cleavage pattern in
      peptidomics data. We found that the same patterns of cleavage were evident in
      both intact human milk and gastric milk samples, demonstrating that the enzyme
      activities that begin in milk persist in the infant stomach. However, the extent
      of enzyme activity is found to vary greatly between the intact milk and gastric
      samples. Overall, we observe that milk-specific proteins are cleaved at higher
      levels in the stomach compared to human milk. Notably, the enzymes we predict
      here only explain 78% of the cleavages uniquely observed in the gastric samples,
      highlighting that further investigation of the specific enzyme activities
      associated with digestion in infants is warranted. 

PMID- 25385260
TI  - A randomized, double-blind, placebo-controlled, twelve-week, dose-ranging study
      of decernotinib, an oral selective JAK-3 inhibitor, as monotherapy in patients
      with active rheumatoid arthritis.
AB  - OBJECTIVE: To assess the efficacy and safety of oral decernotinib (VX-509; Vertex
      Pharmaceuticals) monotherapy in a 12-week, randomized, double-blind, placebo
      controlled, dose-ranging study of patients with rheumatoid arthritis (RA).
      METHODS: Two hundred four adults with active RA who had been unsuccessfully
      treated with >=1 disease-modifying antirheumatic drug were administered placebo
      tablets or decernotinib twice a day at dosages of 25 mg, 50 mg, 100 mg, or 150
      mg. Primary measures of efficacy at week 12 were the response rate according to
      the American College of Rheumatology 20% improvement criteria (ACR20) and mean
      change from baseline in the Disease Activity Score in 28 joints using the C
      reactive protein level (DAS28-CRP). RESULTS: At week 12, the ACR20 response rates
      were 39.0%, 61.0%, 65.0%, and 65.9% in the 25-mg, 50-mg, 100-mg, and 150-mg
      groups, respectively, and were significantly higher in the 50-mg group (P =
      0.007) and the 100-mg and 150-mg groups (P = 0.002) as compared to the response
      rates in the placebo group (29.3%). The mean change from baseline in DAS28-CRP
      was greater in the 50-mg, 100-mg, and 150-mg groups as compared to the placebo
      group (P < 0.001). Decernotinib treatment resulted in higher ACR50 and ACR70
      response rates, more patients with DAS28-CRP scores <2.6, and improvements in the
      Health Assessment Questionnaire disability index as compared to placebo. The most
      common adverse events in any decernotinib group were nausea (6.1%), headache
      (4.3%), an increase in levels of alanine aminotransferase (4.3%), and
      hypercholesterolemia (3.7%). In the groups receiving decernotinib, there was an
      increased risk of infections and increased liver transaminase levels. CONCLUSION:
      Decernotinib was efficacious in improving clinical signs and symptoms of RA at
      week 12 at dosages of 50-150 mg twice a day. Infections and increases in liver
      transaminase and lipid levels were noted as potential safety signals.

PMID- 25385261
TI  - Attachment, penetration and early host defense mechanisms during the infection of
      filamentous brown algae by Eurychasma dicksonii.
AB  - Eurychasma dicksonii is one of the most common and widespread marine pathogens
      and attacks a broad spectrum of more than 45 brown algal species. The present
      study focuses on the mechanism used by the pathogen to attach on the host cell
      wall and force its way into algal cells. Ultrastructural examination revealed a
      needle-like structure which develops within the attached spore and extends along
      its main axis. Particular cell wall modifications are present at the basal part
      of the spore (adhesorium pad) and guide the needle-like tool to penetrate
      perpendicularly the host cell wall. The unique injection mechanism is shared with
      Haptoglossa species which suggests that this is an important characteristic of
      early diverging oomycetes. Furthermore, the encystment and adhesion mechanism of
      E. dicksonii shows significant similarities with other oomycetes, some of which
      are plant pathogens. Staining and immunolabelling techniques showed the
      deposition of beta-1,3-glucans on the host cell wall at the pathogen penetration
      site, a strategy similar to physical responses previously described only in
      infected plant cells. It is assumed that the host defense in terms of callose
      like deposition is an ancient response to infection.

PMID- 25385262
TI  - Kiellands forceps, a timely reminder.

PMID- 25385263
TI  - Towards the serological diagnosis of primary biliary cirrhosis.

PMID- 25385264
TI  - 2D phase contrast blood flow velocity measurements of the thoracic vasculature:
      comparison of the effect of gadofosveset trisodium and gadopentetate dimeglumine.
AB  - The aim of this prospective study is to compare the performance of 2D time
      resolved phase-contrast (PC) MRI prior to and after the administration of an
      intravascular (gadofosveset-trisodium) and extravascular (gadopentetate
      dimeglumine) contrast agent in the same patient in the cardiovascular system.
      This study was approved by the ethics committee (Study-Number-07/Q0704/2) and
      registered with the MedicinesAndHealthcareProductsRegulatoryAgency (MHRA-Study
      Number-28482/0002/001-0001, EudraCT-Number-2006-007042). All patients signed an
      informed consent. 20 patients were examined using a 1.5T MR-scanner and 32
      channel-coil-technology. Gadopentetate-dimeglumine (GdD) and gadofosveset
      trisodium (GdT) were administered in the same patient on consecutive days. Image
      quality, velocity-to-noise-ratios (VNRs) and standard-deviation of blood-flow
      velocities (phase-noise) were compared between GdT, GdD and non-contrast-enhanced
      imaging. On both days pre- and post-contrast-scans were performed. The
      administration of GdT significantly improved the delineation of the perfused
      lumen and the VNR compared to GdD and non-contrast-enhanced imaging. Standard
      deviations of through-plane and in-plane velocity-measurements (phase-noise) were
      significantly reduced after GdT administration (p < 0.05). No significant
      differences (p > 0.05) were measured regarding absolute flow values prior to and
      after the administration of GdD and GdT. PC flow imaging benefits from the
      administration of an intravascular contrast agent by improving the delineation of
      the perfused lumen and reducing phase noise in flow measurements.

PMID- 25385266
TI  - Reliable and powerful laboratory markers of cobalamin deficiency in the newborn:
      plasma and urinary methylmalonic acid.
AB  - BACKGROUND: Diagnosing cobalamin deficiency is critical, given the high
      prevalence of cobalamin deficiency particularly in developing countries.
      Measuring serum cobalamin levels is of limited diagnostic sensitivity, in other
      words its specificity and sensitivity are low. The present study investigated the
      changes in the levels of metabolic markers - plasma homocysteine, plasma
      methylmalonic acid (MMA) and urinary MMA - of cobalamin metabolism. METHODS:
      Plasma cobalamin and serum folic acid were studied in 206 pregnant women over the
      last four prenatal weeks. Plasma cobalamin, folic acid, homocysteine, MMA from
      umbilical cord blood and urinary MMA in newborns were studied. RESULTS: Plasma
      cobalamin values were low in 66% of the mothers. There was a positive correlation
      between maternal and neonatal plasma cobalamin values (r = 0.72, p < 0.001). B12
      was strongly inversely associated with plasma MMA, urine MMA and plasma
      homocysteine. To predict cobalamin deficiency, sensitivities of plasma MMA,
      urinary MMA and homocysteine were 96.4%, 95.6% and 88.2%, respectively. And
      positive predictive values (PPV) were 96.2%, 96.9% and 86% for plasma MMA,
      urinary MMA and plasma homocysteine levels, respectively. CONCLUSION: Plasma MMA
      and urinary MMA B12 are the most robust markers of cobalamin deficiency. As a non
      invasive method, urinary MMA is a sensitive method in demonstrating cobalamin
      deficiency in the newborn.

PMID- 25385265
TI  - TP53 oncomorphic mutations predict resistance to platinum- and taxane-based
      standard chemotherapy in patients diagnosed with advanced serous ovarian
      carcinoma.
AB  - Individual mutations in the tumor suppressor TP53 alter p53 protein function.
      Some mutations create a non-functional protein, whereas others confer oncogenic
      activity, which we term 'oncomorphic'. Since mutations in TP53 occur in nearly
      all ovarian tumors, the objective of this study was to determine the relationship
      of oncomorphic TP53 mutations with patient outcomes in advanced serous ovarian
      cancer patients. Clinical and molecular data from 264 high-grade serous ovarian
      cancer patients uniformly treated with standard platinum- and taxane-based
      adjuvant chemotherapy were downloaded from The Cancer Genome Atlas (TCGA) portal.
      Additionally, patient samples were obtained from the University of Iowa and
      individual mutations were analyzed in ovarian cancer cell lines. Mutations in the
      TP53 were annotated and categorized as oncomorphic, loss of function (LOF), or
      unclassified. Associations between mutation types, chemoresistance, recurrence,
      and progression-free survival (PFS) were calculated. Oncomorphic TP53 mutations
      were present in 21.3% of ovarian cancers in the TCGA dataset. Patients with
      oncomorphic TP53 mutations demonstrated significantly worse PFS, a 60% higher
      risk of recurrence (HR=1.60, 95% confidence intervals 1.09, 2.33, p=0.015), and
      higher rates of platinum resistance (chi(2) test p=0.0024) when compared with
      single nucleotide mutations not categorized as oncomorphic. Furthermore, tumors
      containing oncomorphic TP53 mutations displayed unique protein expression
      profiles, and some mutations conferred increased clonogenic capacity in ovarian
      cancer cell models. Our study reveals that oncomorphic TP53 mutations are
      associated with worse patient outcome. These data suggest that future studies
      should take into consideration the functional consequences of TP53 mutations when
      determining treatment options.

PMID- 25385267
TI  - Arkansas fetal diagnosis and management: identifying and coordinating care for
      anomalous fetuses.
AB  - OBJECTIVE: Describe a novel system of coordinating the identification and
      management of fetal anomalies in a rural state, where there is a large proportion
      of impoverished and Medicaid eligible patients, and centralization of the
      majority of tertiary care resources. METHODS: The Arkansas Fetal Diagnosis and
      Management program was initiated to coordinate the care of anomalous fetuses.
      Data from the beginning of the program (2009) to 2013 was collected and analyzed.
      The data is reported in a descriptive fashion, to report the outcomes of this
      program. The specific type and number of anomalies diagnosed and managed were
      tabulated and analyzed. RESULTS: From 2009 to 2013, data from 1300 pregnancies
      was collected. From 2009 to 2013, there were 7.9%, 10.9%, 15.0%, 18.6%, and 22.3%
      of ultrasound referrals with fetal anomalies. The anomalies were grouped by
      physiologic system, and despite the total numbers increasing each year, the
      frequency and distribution of anomalies remained constant. CONCLUSIONS: The
      Arkansas Fetal Diagnosis and Management Program streamlined the coordination of
      care for pregnancies affected by anomalous fetuses.

PMID- 25385268
TI  - Pregnancy outcomes in women aged 35 years or older with gestational diabetes - a
      registry-based study in Finland.
AB  - OBJECTIVE: To compare pregnancy outcomes of women >= 35 years to women <35 years
      with and without gestational diabetes. METHODS: The data include 230,003 women
      <35 years and 53,321 women >= 35 years and their newborns from 2004 to 2008. In
      multivariate modeling, the main outcome measures were preterm delivery (<28, 28
      31 and 32-36 weeks' gestation), Apgar scores <7 at 5 min, small for gestational
      age (SGA), fetal death, asphyxia, preeclampsia, admission to neonatal intensive
      care unit (NICU), shoulder dystocia and large for gestational age (LGA). RESULTS:
      In comparison to women <35 with normal glucose tolerance, preeclampsia (OR 1.57,
      CI 1.30-1.88), admission to the NICU (OR 3.30, CI 2.94-3.69) and shoulder
      dystocia (OR 2.12, CI 1.05-4.30) were highest in insulin-treated women >= 35
      years. In women >=35, diet- and insulin-treated gestational diabetes mellitus
      (GDM) increased the rates of preeclampsia, shoulder dystocia and admission to
      NICU (OR 3.07 CI 2.73-3.45). The effect of advanced maternal age was observed in
      very preterm delivery (<28 weeks), fetal death, preeclampsia and NICU. The
      increase in preeclampsia was statistically significant. CONCLUSIONS: GDM at
      advanced age is a high risk state and, more specifically, the risk caused by age
      and GDM appear to be increasing in preeclampsia.

PMID- 25385269
TI  - The effect of associated structural malformations in the prediction of
      chromosomal abnormality risk of fetuses with echogenic bowel.
AB  - OBJECTIVE: Our aim is to determine the frequency of chromosomal abnormalities and
      also to identify the role of structural malformations on the chromosomal
      abnormality risk among fetuses with echogenic bowel. METHODS: Over a 6-year
      period fetuses with echogenic bowel (FEB) were retrospectively evaluated. The
      pregnancies with intra-amniotic bleeding history, congenital infection, cystic
      fibrosis and intrauterine growth retardation were excluded from the study. Types
      and frequency of sonographically detected fetal malformations were identified.
      Chromosomal abnormality incidences according to association with soft markers and
      major fetal abnormalities were compared. RESULTS: Of the 281 fetuses with
      echogenic bowel, 105 (37.37%) were isolated, 78 (27.76%) were associated with
      soft markers and 98 (34.87%) were associated with major abnormalities. There were
      30 (10.7%) fetuses with abnormal karyotypes. The chromosomal abnormality rate of
      the groups of isolated FEB, FEB + soft markers and FEB + major abnormalities were
      6.7%, 7.7% and 17.4%, respectively. CONCLUSIONS: Chromosomal abnormality risk in
      fetuses with echogenic bowel should be evaluated according to additional
      sonographic findings. Association of structural malformations increases the
      chromosomal abnormality risk, although this risk is not significant with the
      presence of soft markers alone.

PMID- 25385270
TI  - The treatment of neonatal seizures: focus on Levetiracetam.
AB  - Neonatal crises are a common problem in the first month, where phenobarbital and
      phenytoin are still the most frequently used medication in treatment. Whereas,
      Levetiracetam (LEV) is an antiepileptic drug (AED) with an innovative action. Our
      present review is updated on the current literature regarding the use of LEV in
      neonatal seizures treatment. The available data is analyzed to assess LEV
      pharmacokinetics, efficacy and tolerability in neonatal crises treatment. Several
      clinical trials, prospective and retrospective, comparative and pharmacokinetic
      studies were evaluated in LEV pharmacokinetics, efficacy, dosage, route of
      administration and side effects. Many cases were reported on neonatal seizures
      control in using LEV in certain clinical conditions. In spite of the limitations
      in current studies available, which have evaluated LEV efficacy and safety in
      neonatal crises treatment, the authors still believe that LEV seems to be a
      promising and useful AED in the treatment for neonatal seizures, but likewise
      further studies are required to better define LEV efficacy and tolerability in
      term and preterm neonates. 

PMID- 25385271
TI  - Treatment of rapidly proliferating haemangiomas in newborns with propranolol and
      review of the literature.
AB  - AIM: Infantile haemangiomas (IH) are neoplastic proliferations of endothelial
      cells which occur with an incidence of 10-12%. IH rapidly growing and found in
      cosmetically sensitive areas or complicated with ulcerations are of special
      concern of parents. METHODS: A review of medical charts was performed for
      newborns treated with propranolol because of IH between 2012 and 2013. There were
      two boys and two girls, referred to our department at the age of 2-3 weeks.
      Children were commenced on propranolol 0.5 mg/kg daily and closely monitored. The
      dosage was increased up to a maximum of 2 mg/kg/d and was maintained until the
      lesion had involuted or showed good result. RESULTS: The minimal dosage required
      to achieve involution was 1.5-2.0 mg/kg/d. No rebound growth or complications
      were observed. Three patients showed excellent response with resolution of the
      lesion. Fourth patient showed good result with >50% reduction of IH. CONCLUSIONS:
      Propranolol at 1.5-2.0 mg/kg/d is effective and safe for treating IH in our
      series of newborn patients. Treatment should be maintained until the lesion is
      involuted or shows good cosmetic result. Still there is need for larger scale
      studies confirming the safety and efficacy of propranolol in treatment of
      haemangiomas in newborns.

PMID- 25385272
TI  - Single screening questions for cognitive impairment in older people: a systematic
      review.
AB  - BACKGROUND AND OBJECTIVE: Single-item screening questions may be a practical
      first step in screening for cognitive problems in older people. A form of single
      item cognitive assessment is proposed in the NHS England and Wales dementia
      strategy. We aimed to provide a review and synthesis of the evidence regarding
      the performance of single-item tests for detection of cognitive impairment.
      DESIGN: This review used Cochrane diagnostic test accuracy procedures. Two
      independent researchers searched for relevant papers across multiple, cross
      disciplinary electronic databases using previously validated search strings. Our
      index test was any single screening question for cognitive impairment, including
      factor analysis of multi-item tools. Our reference standards included clinical
      diagnosis and multi-domain cognitive assessments. RESULTS: From 884 titles, 11
      studies were identified as eligible for inclusion. Four studies were graded low
      risk of bias and recruited a representative patient sample. Five papers described
      a single screening question for cognitive impairment with each using a different
      question. Sensitivity ranged from 26 to 96% and specificity from 45 to 100%. Six
      papers described the component analysis of multiple item tools with broadly
      worded single questions ('decline in memory function', 'changes in ability to
      think and reason' or 'learning new things') performing best. CONCLUSION:
      Informant-based, single-item screening questions show promise for detecting
      cognitive impairment. However, there was substantial heterogeneity in format and
      application of single-item screens, and several studies were of poor
      methodological quality. Currently, there is insufficient evidence to support
      routine screening using a single-item approach.

PMID- 25385273
TI  - Bournewood revisited--do recent changes to the law regarding Deprivation of
      Liberty Safeguards represent an opportunity or an opportunity cost?

PMID- 25385275
TI  - VariSNP, a benchmark database for variations from dbSNP.
AB  - For development and evaluation of methods for predicting the effects of
      variations, benchmark datasets are needed. Some previously developed datasets are
      available for this purpose, but newer and larger benchmark sets for benign
      variants have largely been missing. VariSNP datasets are selected from dbSNP.
      These subsets were filtered against disease-related variants in the ClinVar,
      UniProtKB/Swiss-Prot, and PhenCode databases, to identify neutral or
      nonpathogenic cases. All variant descriptions include mapping to reference
      sequences on chromosomal, genomic, coding DNA, and protein levels. The datasets
      will be updated with automated scripts on a regular basis and are freely
      available at http://structure.bmc.lu.se/VariSNP.

PMID- 25385274
TI  - The value of routine chest radiographs after minimally invasive cardiac surgery:
      an observational cohort study.
AB  - BACKGROUND: Chest radiographs (CXRs) are obtained frequently in postoperative
      cardiac surgery patients. The diagnostic and therapeutic efficacy of routine CXRs
      is known to be low and the discussion regarding the safety of abandoning these
      CXRs after cardiac surgery is still ongoing. We investigated the value of routine
      CXRs directly after minimally invasive cardiac surgery. METHODS: We prospectively
      included all patients who underwent minimally invasive cardiac surgery by port
      access, ministernotomy or bilateral video-assisted thoracoscopy (VATS) in the
      year 2012. A direct postoperative CXR was performed on all patients at ICU
      arrival. All CXR findings were noted, including whether they led to an
      intervention or not. The results were compared to the postoperative CXR results
      in patients who underwent conventional cardiac surgery by full median sternotomy
      over the same period. MAIN RESULTS: A total of 249 consecutive patients were
      included. Most of these patients underwent valve surgery, rhythm surgery or a
      combination of both. The diagnostic efficacy for minor findings was highest in
      the port access and bilateral VATS groups (56% and 63% versus 28% and 45%) (p <
      0.005). The diagnostic efficacy for major findings was also higher in these
      groups (8.9% and 11% versus 4.3% and 3.8%) (p = 0.010). The need for an
      intervention was most common after minimally invasive surgery by port access,
      although this difference was not statistically significant (p = 0.056).
      CONCLUSIONS: The diagnostic efficacy of routine CXRs performed after minimally
      invasive cardiac surgery by port access or bilateral VATS is higher than the
      efficacy of CXRs performed after conventional cardiac surgery. A routine CXR
      after these procedures should still be considered.

PMID- 25385276
TI  - Flexible processing and the design of grammar.
AB  - We explore the consequences of letting the incremental and integrative nature of
      language processing inform the design of competence grammar. What emerges is a
      view of grammar as a system of local monotonic constraints that provide a direct
      characterization of the signs (the form-meaning correspondences) of a given
      language. This "sign-based" conception of grammar has provided precise solutions
      to the key problems long thought to motivate movement-based analyses, has
      supported three decades of computational research developing large-scale grammar
      implementations, and is now beginning to play a role in computational
      psycholinguistics research that explores the use of underspecification in the
      incremental computation of partial meanings. 

PMID- 25385279
TI  - Comment on 'A justification for less restrictive guidelines on the use of
      metformin in stable chronic renal failure'.

PMID- 25385277
TI  - Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy.
AB  - Genomic alterations may make cancer cells more dependent than normal cells on
      mechanisms of proteostasis, including protein folding and degradation. This
      proposition is the basis for the clinical use of proteasome inhibitors to treat
      multiple myeloma and mantle cell lymphoma. However, proteasome inhibitors have
      not proved effective in treating other cancers, and this has called into question
      the general applicability of this approach. Here, I consider possible
      explanations for this apparently limited applicability, and discuss whether
      inhibiting other broadly acting components of the ubiquitin-proteasome system -
      including ubiquitin-activating enzyme and the AAA-ATPase p97/VCP - might be more
      generally effective in cancer therapy. 

PMID- 25385278
TI  - Impact of early use of lenalidomide and low-dose dexamethasone on clinical
      outcomes in patients with relapsed/refractory multiple myeloma.
AB  - We retrospectively investigated the prognostic factor of lenalidomide plus low
      dose dexamethasone (Rd) in Japanese patients with refractory or relapsed multiple
      myeloma (RRMM) registered in the Kansai Myeloma Forum from January 2006 to
      December 2013. A total of 140 patients were analyzed. The median age was 66
      years. The overall response rate was 68.6 %, including 33.1 % with a better than
      very good partial response. At 13.0 months median follow-up, the median overall
      survival (OS) and progression-free survival (PFS) were 34.2 and 17.0 months,
      respectively. In univariate analyses, patients with one or two prior therapies
      had significantly longer OS (41.2 vs. 21.5 months; P = 0.002) and PFS (29.0 vs.
      13.0 months; P = 0.006) than patients treated with three or more prior therapies.
      Prior use of thalidomide was associated with significantly shorter PFS (19.0 vs.
      16.0 months; P = 0.045). The prior use of bortezomib or high-dose therapy with
      stem cell transplantation, and the International Staging System had no impact on
      long-term outcome. Multivariate analysis showed that only the number of prior
      therapies was a significant predictor of both OS and PFS. Our findings suggest
      that greater benefit may occur when Rd therapy is used at the first or second
      relapse in RRMM.

PMID- 25385280
TI  - Effect of HGF on the apoptosis of rat corpus cavernosum smooth muscle cells
      induced by TGFbeta1.
AB  - Corpus cavernosum smooth muscle cells (CCSMCs) are important functional cells for
      penile erection. We evaluated the effect of transforming growth factor beta1
      (TGFbeta1) and hepatocyte growth factor (HGF) on the viability and apoptosis of
      CCSMCs in vitro. CCSMCs from healthy male Sprague Dawley rats were randomly
      divided into four groups: a negative control group, a TGFbeta1 group, a HGF group
      and a HGF+ TGFbeta1 group. Differences in cell viability and apoptosis among
      groups were observed by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium
      bromide (MTT) assay and flow cytometry. Western blot was used to detect the
      change of apoptosis-related proteins. The level of reactive oxygen species (ROS)
      was detected by colorimetry. In the TGFbeta1 group, the MTT values were obviously
      decreased at 12 h, 24 h, 48 h-0.320, 0.383 and 0.432 respectively. However,
      compared with the normal group, the apoptosis index was markedly increased,
      reaching 26.86% at the 48-h time point. After TGFbeta1 treatment, the levels of
      cleaved caspase-3 and p-Smad2 were increased in the cells, but the levels of Bcl
      xL, Bcl-2 and p-Akt were significantly lower. However, HGF co-treatment partially
      reversed these changes and could decrease the intracellular ROS level while
      increasing the Akt phosphorylation level. These results indicate that TGFbeta1
      might induce apoptosis of CCSMCs in vitro and that HGF could interfere with the
      above process through downregulation of apoptosis signalling and oxidative stress
      reaction.

PMID- 25385283
TI  - Spatial structuring of a supramolecular hydrogel by using a visible-light
      triggered catalyst.
AB  - Spatial control over the self-assembly of synthetic molecular fibers through the
      use of light-switchable catalysts can lead to the controlled formation of
      micropatterns made up of hydrogel structures. A photochromic switch, capable of
      reversibly releasing a proton upon irradiation, can act as a catalyst for in situ
      chemical bond formation between otherwise soluble building blocks, thereby
      leading to fiber formation and gelation in water. The use of a photoswitchable
      catalyst allows control over the distribution as well as the mechanical
      properties of the hydrogel material. By using homemade photomasks, spatially
      structured hydrogels were formed starting from bulk solutions of small molecule
      gelator precursors through light-triggered local catalyst activation. 

PMID- 25385281
TI  - Evaluation of a clinical tool for early etiology identification in status
      epilepticus.
AB  - OBJECTIVES: Because early etiologic identification is critical to select
      appropriate specific status epilepticus (SE) management, we aim to validate a
      clinical tool we developed that uses history and readily available investigations
      to guide prompt etiologic assessment. METHODS: This prospective multicenter study
      included all adult patients treated for SE of all but anoxic causes from four
      academic centers. The proposed tool is designed as a checklist covering frequent
      precipitating factors for SE. The study team completed the checklist at the time
      the patient was identified by electroencephalography (EEG) request. Only
      information available in the emergency department or at the time of in-hospital
      SE identification was used. Concordance between the etiology indicated by the
      tool and the determined etiology at hospital discharge was analyzed, together
      with interrater agreement. RESULTS: Two hundred twelve patients were included.
      Concordance between the etiology hypothesis generated using the tool and the
      finally determined etiology was 88.7% (95% confidence interval (CI) 86.4-89.8)
      (kappa = 0.88). Interrater agreement was 83.3% (95% CI 80.4-96) (kappa = 0.81).
      SIGNIFICANCE: This tool is valid and reliable for identification early the
      etiology of an SE. Physicians managing patients in SE may benefit from using it
      to identify promptly the underlying etiology, thus facilitating selection of the
      appropriate treatment.

PMID- 25385284
TI  - Summer drought alters carbon allocation to roots and root respiration in mountain
      grassland.
AB  - Drought affects the carbon (C) source and sink activities of plant organs, with
      potential consequences for belowground C allocation, a key process of the
      terrestrial C cycle. The responses of belowground C allocation dynamics to
      drought are so far poorly understood. We combined experimental rain exclusion
      with (13)C pulse labelling in a mountain meadow to analyse the effects of summer
      drought on the dynamics of belowground allocation of recently assimilated C and
      how it is partitioned among different carbohydrate pools and root respiration.
      Severe soil moisture deficit decreased the ecosystem C uptake and the amounts and
      velocity of C allocated from shoots to roots. However, the proportion of recently
      assimilated C translocated belowground remained unaffected by drought. Reduced
      root respiration, reflecting reduced C demand under drought, was increasingly
      sustained by C reserves, whilst recent assimilates were preferentially allocated
      to root storage and an enlarged pool of osmotically active compounds. Our results
      indicate that under drought conditions the usage of recent photosynthates is
      shifted from metabolic activity to osmotic adjustment and storage compounds.

PMID- 25385285
TI  - Effect of ulinastatin on the expression and distribution of high mobility group
      box 1 in human colon carcinoma cells in vitro.
AB  - The aim of the present study was to investigate the in vitro effects of
      ulinastatin (UTI) on the proliferation, invasion, apoptosis, expression and
      distribution of high mobility group box 1 (HMGB1) and the expression of nuclear
      factor kappaB (NF-kappaB) in human colon carcinoma LoVo cells. The cells were
      divided into control (untreated), UTI1 (400 U/ml UTI), UTI2 (800 U/ml UTI) and
      UTI3 (1,600 U/ml UTI) groups. The cell proliferation, invasion, apoptosis and the
      gene and protein expression of HMGB1 and NF-kappaB were detected using a
      tetrazolium assay, Transwell cell invasion assays, a caspase-3 activity assay,
      western blot analysis and reverse transcription quantitative polymerase chain
      reaction, respectively. The distribution of HMGB1 was detected using
      immunofluorescence. LoVo cell proilferation decreased the most in the UTI3 group
      followed, in order, by the UTI2, UTI1 and control groups. UTI inhibited invasion
      in LoVo cells and the inhibitory effect was enhanced as the UTI concentration
      increased. The activity of caspase-3 increased the least in the control group
      followed, in order, by the UTI1, UTI2 and UTI3 groups. UTI inhibited the
      expression of HMGB1 and NF-kappaB, and decreased the cytoplasmic distribution of
      HMGB1. Thus, UTI inhibited LoVo cell proliferation and induced LoVo cell
      apoptosis, the mechanism of which may be associated with a decreased in the
      expression of HMGB1 and NF-kappaB, and the cytoplasmic distribution of HMGB1.

PMID- 25385286
TI  - MicroRNAs in kidney physiology and disease.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene
      expression. They have important roles during kidney development, homeostasis and
      disease. In particular, miRNAs participate in the onset and progression of
      tubulointerstitial sclerosis and end-stage glomerular lesions that occur in
      various forms of chronic kidney disease (CKD). Therefore, miRNAs represent
      potential new therapeutic targets for a debilitating disease that continues to
      increase in prevalence worldwide and for which fully effective therapies are
      lacking. Several lines of research aimed at improving common CKD diagnostic tools
      and avoiding invasive kidney biopsies have also identified circulating miRNAs as
      possible diagnostic and even prognostic biomarkers of kidney disease. This Review
      discusses current understanding of the function of miRNAs in CKD, focusing on
      functions specifically involved in the transforming growth factor beta1 pathway,
      which is activated in CKD. miRNAs that, according to available evidence, seem to
      be involved in diabetic nephropathy, IgA nephropathy, lupus nephritis, polycystic
      kidney disease and graft rejection, are also discussed. 

PMID- 25385288
TI  - Autophagy-linked FYVE protein (Alfy) promotes autophagic removal of misfolded
      proteins involved in amyotrophic lateral sclerosis (ALS).
AB  - Autophagy-linked FYVE (Alfy) is a protein implicated in the selective degradation
      of aggregated proteins. In our present study, we found that Alfy was recruited
      into the aggregated G93A-SOD1 in transgenic mice with amyotrophic lateral
      sclerosis (ALS). We demonstrated that Alfy overexpression could decrease the
      expression of mutant proteins via the autophagosome-lysosome pathway, and
      thereby, the toxicity of mutant proteins was reduced. The clearance of the mutant
      proteins in NSC34 cells was significantly inhibited in an Alfy knockdown cellular
      model. We therefore deduced that Alfy translocalization likely is involved in the
      pathogenesis of ALS. Alfy may be developed into a useful target for ALS therapy.

PMID- 25385287
TI  - Mechanisms and biological functions of autophagy in diseased and ageing kidneys.
AB  - Autophagy degrades pathogens, altered organelles and protein aggregates, and is
      characterized by the sequestration of cytoplasmic cargos within double-membrane
      limited vesicles called autophagosomes. The process is regulated by inputs from
      the cellular microenvironment, and is activated in response to nutrient scarcity
      and immune triggers, which signal through a complex molecular network. Activation
      of autophagy leads to the formation of an isolation membrane, recognition of
      cytoplasmic cargos, expansion of the autophagosomal membrane, fusion with
      lysosomes and degradation of the autophagosome and its contents. Autophagy
      maintains cellular homeostasis during stressful conditions, dampens inflammation
      and shapes adaptive immunity. A growing body of evidence has implicated autophagy
      in kidney health, ageing and disease; it modulates tissue responses during acute
      kidney injuries, regulates podocyte homeostasis and protects against age-related
      renal disorders. The renoprotective functions of autophagy in epithelial renal
      cells and podocytes are mostly mediated by the clearance of altered mitochondria,
      which can activate inflammasomes and apoptosis, and the removal of protein
      aggregates, which might trigger inflammation and cell death. In translational
      terms, autophagy is undoubtedly an attractive target for developing new
      renoprotective treatments and identifying markers of kidney injury. 

PMID- 25385290
TI  - The contribution of different information sources to identify adverse effects of
      a medical device: a case study using a systematic review of spinal fusion.
AB  - BACKGROUND: The most effective sources to search to identify adverse effects data
      for medical devices are currently unknown. METHODS: The included studies from a
      systematic review of the safety of recombinant human bone morphogenetic protein-2
      (rhBMP-2) for spinal fusion were used for analysis. For each source searched, a
      record was made for each relevant publication of whether it was retrieved by the
      search strategy used and whether it was available in the database but not
      retrieved. To account for multiple publications of the same study, a record was
      made of the relevant studies identified. The sensitivity, precision, and number
      needed to read were calculated as well as the minimum combination of sources to
      identify all the publications or studies. RESULTS: There were eighty-two
      publications (forty-nine studies) included in the systematic review. Only one
      article was available in a database searched but not retrieved by our search
      strategy. Science Citation Index (SCI) and EMBASE both achieved the highest
      sensitivity (62 percent), followed closely by MEDLINE/PubMED (56 percent). With
      the search strategies used, the minimum combination of sources needed to identify
      all the publications was SCI, EMBASE, CENTRAL, and either MEDLINE or PubMED, in
      addition to reference checking, contacting authors and an automated current
      awareness service. In relation to identifying all the relevant studies, the
      minimum combination of studies was similar with the exclusion of CENTRAL.
      CONCLUSIONS: To identify all the relevant publications or studies included in
      this case study systematic review, several different sources needed to be
      searched.

PMID- 25385291
TI  - Maxwell's Daemon: information versus particle statistics.
AB  - Maxwell's daemon is a popular personification of a principle connecting
      information gain and extractable work in thermodynamics. A Szilard Engine is a
      particular hypothetical realization of Maxwell's daemon, which is able to extract
      work from a single thermal reservoir by measuring the position of particle(s)
      within the system. Here we investigate the role of particle statistics in the
      whole process; namely, how the extractable work changes if instead of classical
      particles fermions or bosons are used as the working medium. We give a unifying
      argument for the optimal work in the different cases: the extractable work is
      determined solely by the information gain of the initial measurement, as measured
      by the mutual information, regardless of the number and type of particles which
      constitute the working substance. 

PMID- 25385289
TI  - Interplay of physical mechanisms and biofilm processes: review of microfluidic
      methods.
AB  - Bacteria in natural and artificial environments often reside in self-organized,
      integrated communities known as biofilms. Biofilms are highly structured entities
      consisting of bacterial cells embedded in a matrix of self-produced extracellular
      polymeric substances (EPS). The EPS matrix acts like a biological 'glue' enabling
      microbes to adhere to and colonize a wide range of surfaces. Once integrated into
      biofilms, bacterial cells can withstand various forms of stress such as
      antibiotics, hydrodynamic shear and other environmental challenges. Because of
      this, biofilms of pathogenic bacteria can be a significant health hazard often
      leading to recurrent infections. Biofilms can also lead to clogging and material
      degradation; on the other hand they are an integral part of various environmental
      processes such as carbon sequestration and nitrogen cycles. There are several
      determinants of biofilm morphology and dynamics, including the genotypic and
      phenotypic states of constituent cells and various environmental conditions.
      Here, we present an overview of the role of relevant physical processes in
      biofilm formation, including propulsion mechanisms, hydrodynamic effects, and
      transport of quorum sensing signals. We also provide a survey of microfluidic
      techniques utilized to unravel the associated physical mechanisms. Further, we
      discuss the future research areas for exploring new ways to extend the scope of
      the microfluidic approach in biofilm studies. 

PMID- 25385293
TI  - Clinical and pharmacokinetic evaluation of risperidone for the management of
      autism spectrum disorder.
AB  - INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder
      that is often accompanied by psychiatric comorbidity. Although there is no
      medication currently available to treat the core symptoms of ASD, risperidone was
      the first drug to be approved for use in ASD and is still the best established
      psychopharmacological option for the treatment of irritability and behavioral
      problems in ASD. AREAS COVERED: This article gives an overview of the
      pharmacokinetic profile of risperidone and a comprehensive review of treatment
      studies regarding the use of risperidone in ASD. EXPERT OPINION: Ample evidence
      supports the short-term use of risperidone for treating irritability and
      behavioral problems in ASD. Risperidone also shows promise in treating symptoms
      often associated with ASD, such as stereotypical behavior, social difficulties,
      hyperactivity and cognitive problems. However, several adverse effects have been
      identified; most are mild or moderate and well manageable, but weight gain and
      metabolic changes are a considerable concern. Therefore, risperidone should in
      our view be seen as 'a last resort', only justified for the short-term treatment
      of serious behavioral problems, which have failed to respond sufficiently to
      behavioral interventions. Future studies should investigate long-term effects of
      risperidone and factors that facilitate individual risk-benefit analyses before
      treatment.

PMID- 25385295
TI  - The potential of human umbilical cord-derived mesenchymal stem cells as a novel
      cellular therapy for multiple sclerosis.
AB  - Multiple sclerosis (MS) is a complex disease of neurological disability,
      affecting more than 300 out of every 1 million people in the world. The purpose
      of the study was to evaluate the therapeutic effects of human umbilical cord
      derived mesenchymal stem cell (hUC-MSC) transplantation in MS patients. Twenty
      three patients were enrolled in this study, and 13 of them were given hUC-MSC
      therapy at the same time as anti-inflammatory treatment, whereas the control
      patients received the anti-inflammatory treatment only. Treatment schedule
      included 1,000 mg/kg of methylprednisolone intravenously (IV) daily for 3 days
      and then 500 mg/kg for 2 days, followed by oral prednisone 1 mg/kg/day for 10
      days. The dosage of prednisone was then reduced by 5 mg every 2 weeks until
      reaching a 5-mg/day maintenance dosage. Intravenous infusion of hUC-MSCs was
      applied three times in a 6-week period for each patient. The overall symptoms of
      the hUC-MSC-treated patients improved compared to patients in the control group.
      Both the EDSS scores and relapse occurrence were significantly lower than those
      of the control patients. Inflammatory cytokines were assessed, and the data
      demonstrated a shift from Th1 to Th2 immunity in hUC-MSC-treated patients. Our
      data demonstrated a high potential for hUC-MSC treatment of MS. This manuscript
      is published as part of the International Association of Neurorestoratology
      (IANR) special issue of Cell Transplantation. 

PMID- 25385296
TI  - Diastolic Dyssynchrony Differences in Patients with Single Right Ventricles vs.
      Control Patients.
AB  - AIMS: Diastolic dyssynchrony is increasingly being recognized as another marker
      for possible adverse cardiac events. Minimal data exist in hypoplastic left heart
      syndrome (HLHS) patients. The goal of this study was to determine if there were
      differences in diastolic dyssynchrony in patients with HLHS vs. control patients.
      METHODS/RESULTS: Tissue Doppler imaging (TDI) and strain rate (SR) analysis of
      the right ventricle in HLHS and control patients were performed. Time interval
      from onset of QRS complex on electrocardiography to peak TDI e' wave was
      obtained. Differences in intervals were calculated: QRSe'(RV) - QRSe'(IVS) and
      QRSe'(RV) - QRSe'LV). Time interval from onset of QRS to peak strain rate early
      diastolic wave (SRe) was obtained for the six-segment model RV. Standard
      deviation of the six SRe time intervals was calculated. t-tests were performed to
      determine if differences were present between groups. Sixty patients were studied
      (35 HLHS, 25 control). There were no significant differences between HLHS and
      control patients in age (6.5 +/- 3.2 years vs. 6.1 +/- 2.6 years) or heart rate
      (91 +/- 22 bpm vs. 91 +/- 13 bpm), respectively. There were no significant
      differences between HLHS and control patients in QRSe'(RV) - QRSe'(IVS) (19.9 +/-
      15.4 ms vs. 23.3 +/- 13.6 ms) and QRSe'(RV) - QRSe'(LV) (20.7 +/- 13.8 vs. 22.8
      +/- 14.6 ms), respectively. There was a significant difference in SRe standard
      deviation between the HLHS and control patients (25.3 +/- 12.4 ms vs. 15.5 +/-
      6.9 ms, P = .0007), respectively. CONCLUSION: Patients with HLHS had increased
      diastolic dyssynchrony compared with control patients as measured via deformation
      analysis. Future studies are needed to determine the significance of these
      findings.

PMID- 25385297
TI  - Association of TGF-beta1 -509C/T, +869T/C, and +915G/C polymorphisms with
      periodontitis susceptibility.
AB  - OBJECTIVES: To investigate the potential association of TGF-beta1 -509C/T
      (rs1800469), +869T/C (rs1800470), and +915G/C (rs1800471) polymorphisms with
      susceptibility to periodontitis. MATERIALS AND METHODS: Several electronic
      databases were searched for eligible articles. Odds ratios (ORs) along with their
      95% confidence intervals (CIs) were calculated to assess the strength of
      relationship between the TGF-beta1 polymorphisms and periodontitis risk. RESULTS:
      Eleven studies were searched without any language restriction. Pooled estimates
      showed that TGF-beta1 -509C/T polymorphism was associated with decreased risk of
      periodontitis. Subgroup analysis revealed that -509C/T T allele was associated
      with decreased risk of chronic periodontitis (CP) in Asians (T allele vs C
      allele: OR = 0.81, 95% CI = 0.69-0.97, Pheterogeneity = 0.25). Furthermore, the
      +915G/C CC genotype might be associated with elevated risk of CP in Caucasians
      (CC vs GG: OR = 9.14, 95% CI = 1.01-82.50, Pheterogeneity = 0.49). Concerning
      +869T/C polymorphism, no evidence of significant association was identified.
      CONCLUSION: This meta-analysis suggested that TGF-beta1 -509C/T T allele was
      associated with decreased risk of CP in Asians, while +915G/C CC genotype might
      contribute to increased CP risk in Caucasians. Replication studies of our results
      in independent large populations are necessary to validate this association in
      diverse populations.

PMID- 25385294
TI  - Sustained beta-catenin activity in dermal fibroblasts promotes fibrosis by up
      regulating expression of extracellular matrix protein-coding genes.
AB  - Fibrosis is an end-stage response to tissue injury that is associated with loss
      of organ function as a result of excess extracellular matrix (ECM) production by
      fibroblasts. In skin, pathological fibrosis is evident during keloid scar
      formation, systemic sclerosis (SSc) and morphea. Dermal fibroblasts in these
      fibrotic diseases exhibit increased Wnt/beta-catenin signalling, a pathway that
      is sufficient to cause fibrosis in mice. However, in the context of this complex
      pathology, the precise pro-fibrotic consequences of Wnt/beta-catenin signalling
      are not known. We found that expression of stabilized beta-catenin in mouse
      dermal fibroblasts resulted in spontaneous, progressive skin fibrosis with
      thickened collagen fibres and altered collagen fibril morphology. The fibrotic
      phenotype was predominated by resident dermal fibroblasts. Genome-wide profiling
      of the fibrotic mouse dermis revealed elevated expression of matrix-encoding
      genes, and the promoter regions of these genes were enriched for Tcf/Lef family
      transcription factor binding sites. Additionally, we identified 32 beta-catenin
      responsive genes in our mouse model that are also over-expressed in human
      fibrotic tissues and poised for regulation by Tcf/Lef family transcription
      factors. Therefore, we have uncovered a matrix-regulatory role for stabilized
      beta-catenin in fibroblasts in vivo and have defined a set of beta-catenin
      responsive genes with relevance to fibrotic disease.

PMID- 25385298
TI  - Association of achondroplasia with Down syndrome: difficulty in prenatal
      diagnosis by sonographic and 3-D helical computed tomographic analyses.
AB  - Achondroplasia and Down syndrome are relatively common conditions individually.
      But co-occurrence of both conditions in the same patient is rare and there have
      been no reports of fetal analysis of this condition by prenatal sonographic and
      three-dimensional (3-D) helical computed tomography (CT). Prenatal sonographic
      findings seen in persons with Down syndrome, such as a thickened nuchal fold,
      cardiac defects, and echogenic bowel were not found in the patient. A prenatal 3
      D helical CT revealed a large head with frontal bossing, metaphyseal flaring of
      the long bones, and small iliac wings, which suggested achondroplasia. In a case
      with combination of achondroplasia and Down syndrome, it may be difficult to
      diagnose the co-occurrence prenatally without typical markers of Down syndrome. 

PMID- 25385299
TI  - Three multi-nuclear clusters and one infinite chain induced by a pendant 4-butyl
      1H-pyrazole ligand for modification of Keggin anions.
AB  - By utilizing pendant 4-butyl-1H-pyrazole (Hbpz) with an alkyl "tail"--(CH2)3CH3,
      four Keggin-based complexes containing different transition metal multi-nuclear
      clusters and an infinite chain were hydrothermally synthesized and structurally
      characterized, [Cu(I)4(bpz)4(pz)2(H6PW11Cu(II)O39)2].10H2O (1),
      [Cu(II)2(bpz)2(H2O)2(H3PCu0.5Mo11.5O40)].3H2O (2),
      [Ag3(bpz)2(pz)(H4SiW12O40)].4H2O (3) and [Ag5(bpz)4(H5/2PMo12O40)2].6H2O (4) (pz
      = pyrazole). Compound 1 contains a tetra-nuclear cluster [Cu(I)4(bpz)4(pz)2](2-),
      in which four Cu(I) ions are fixed by four bpz and two pz ligands. These clusters
      are linked by Keggin anion dimers to form a 2D layer. In compound 2, the ptz
      ligands fuse the Cu(II) ions and an infinite 1D metal-organic chain is
      constructed with the Keggin anions hanging up and down covalently. Compound 3 has
      a planar triangle tri-nuclear cycle [Ag3(bpz)2(pz)] with three Ag(I) as cores.
      These cycles build a 3D framework of 3 through the further linkages of Keggin
      anions and Ag-Ag bonds. In compound 4, there exist discrete [Ag5(bpz)4](+)
      clusters with four bpz ligands fused by five Ag(I) cores, which are linked by
      Keggin anions alternately to form a 1D chain. Adjacent chains share the Ag-O
      bonds and a 2D layer is constructed. The bpz ligand is firstly introduced into
      the POM field and its successive two N donors are essential for the construction
      of multi-nuclear clusters and an infinite chain of 1-4. Additionally, the
      electrochemical and photocatalytic properties of the title compounds have been
      investigated.

PMID- 25385300
TI  - A case of late lymph node metastasis after three endoscopic mucosal resections of
      intramucosal gastric cancers.
AB  - We describe a patient with solitary lymph node (LN) metastasis after three
      endoscopic mucosal resections (EMRs) in which a gastrointestinal stromal tumor
      was difficult to differentiate from the carcinoid and lymphoma tumors. A 77-year
      old man underwent three EMRs at 62, 72, and 75 years of age, and all resections
      were determined to be curative. However, 2 years after the last EMR, screening
      abdominal ultrasonography detected a 20-mm solitary tumor at the lesser curvature
      of the upper stomach. Laparoscopic tumor resection confirmed the pathological
      diagnosis. Intraoperative pathological diagnosis showed that the adenocarcinoma
      was compatible with recurrence of gastric cancer; thus, total gastrectomy with D1
      lymphadenectomy was performed. Metastasis was not recognized by pathological
      examination but was detected by preoperative radiological examinations of the LN.
      We report a rare recurrence case after several EMRs of intramucosal gastric
      cancers. 

PMID- 25385303
TI  - Atrial natriuretic peptide protects against cisplatin-induced acute kidney
      injury.
AB  - PURPOSE: Cisplatin is an effective chemotherapeutic agent used in the treatment
      of a wide variety of malignancies. Acute kidney injury (AKI) is the major
      toxicity associated with cisplatin and sometimes necessitates a reduction in dose
      or discontinuation of treatment. Atrial natriuretic peptide (ANP) is secreted by
      the heart and exerts a wide range of renoprotective effects, including anti
      inflammatory activity. The objective of this study was to investigate the
      protective effects of ANP on cisplatin-induced AKI in mice. METHODS: Mice were
      randomly divided into three groups: control, cisplatin (20 mg/kg,
      intraperitoneal)/vehicle treatment, and cisplatin/ANP (1.5 MUg/kg/min via osmotic
      pump, subcutaneous) treatment. At 72 h after cisplatin injection, serum blood
      urea nitrogen and creatinine, urine albumin/creatinine, and renal expression of
      mRNAs encoding tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6,
      intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and
      transforming growth factor (TGF)-beta were measured using real-time polymerase
      chain reaction. Histological changes were also evaluated. RESULTS: ANP treatment
      significantly attenuated cisplatin-induced increases in serum blood urea nitrogen
      and creatinine, urine albumin/creatinine, and renal expression of IL-1beta, IL-6,
      intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 mRNAs.
      Cisplatin-induced renal dysfunction and renal tubular necrosis were thus
      attenuated by ANP treatment. CONCLUSIONS: Our results indicate that ANP exhibits
      a protective effect against cisplatin-induced AKI in mice. ANP may thus be of
      value in prophylactic strategies aimed at mitigating the adverse effects
      associated with chemotherapy agents, including cisplatin.

PMID- 25385305
TI  - Heroin substitute treatment should not be time limited, says report commissioned
      by government.

PMID- 25385304
TI  - Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive
      mice developing aortic aneurysm.
AB  - Angiotensin-II and oxidative stress are involved in the genesis of aortic
      aneurysms, a phenomenon exacerbated by endothelial nitric oxide synthase (eNOS)
      deletion or uncoupling. The purpose of this work was to study the endothelial
      function in wild-type C57BL/6 (BL) and transgenic mice expressing the h
      angiotensinogen and h-renin genes (AR) subjected to either a control, or a high
      salt diet plus a treatment with a NO-synthase inhibitor, N-omega-nitro-L-arginine
      methyl-ester (L-NAME; BLSL and ARSL). BLSL showed a moderate increase in blood
      pressure, while ARSL became severely hypertensive. Seventy-five percent of ARSL
      developed aortic aneurysms, characterized by major histo-morphological changes
      and associated with an increase in NADP(H) oxidase-2 (NOX2) expression.
      Contractile responses (KCl, norepinephrine, U-46619) were similar in the four
      groups of mice, and relaxations were not affected in BLSL and AR. However, in
      ARSL, endothelium-dependent relaxations (acetylcholine, UK-14304) were
      significantly reduced, and this dysfunction was similar in aortae without or with
      aneurysms. The endothelial impairment was unaffected by catalase, superoxide
      dismutase mimetic, radical scavengers, cyclooxygenase inhibition, or TP-receptor
      blockade and could not be attributed to sGC oxidation. Thus, ARSL is a severe
      hypertension model developing aortic aneurysm. A vascular dysfunction, involving
      both endothelial (reduced role of NO) and smooth muscle cells, precedes aneurysms
      formation and, paradoxically, does not appear to involve oxidative stress. 

PMID- 25385307
TI  - Relevance of Water Temperature, Apparatus, and Age to Children's Pain during the
      Cold Pressor Task.
AB  - BACKGROUND: Effective use of experimental pain in research depends on a thorough
      understanding of factors influencing their use. Although studies using the cold
      pressor task (CPT) have critically advanced our knowledge of pain mechanisms,
      assessment, and management in adults and children, the impact of identified
      methodological variability in its use is not known (ie, water temperature and
      apparatus); furthermore, whether methodological variations differentially impact
      children across development. METHODS: Pain outcomes were examined in 113 healthy
      children from three age groups (8- to 9-, 10- to 11-, and 12- to 14-year-olds)
      who completed three CPTs at different water temperatures (5, 7, 10 degrees C) in
      counterbalanced order. Children were randomly assigned to one of two apparatus
      (ice- vs. electric-cooled) for all CPTs. Children's hand was warmed to its
      baseline temperature between CPTs. RESULTS: Colder water (2 to 3 degrees C
      decreases) was associated with significantly higher pain intensity and
      unpleasantness, and lower pain tolerance and threshold. Older children (12 to 14
      years) reported significantly worse pain intensity and unpleasantness as compared
      to 8- to 9-year-olds, likely due to longer pain tolerance. Pain outcomes in 10-
      to 11-year-olds fell between the other age groups, with significant differences
      for pain unpleasantness and pain tolerance (at 10 degrees C). Higher pain-related
      fear and pain unpleasantness occurred with the electric-cooled apparatus. Girls
      had higher pain tolerance and threshold at all temperatures. CONCLUSIONS: These
      results provide critically important information about water temperature,
      apparatus, and child age on CPT pain responding. It informs design of future CPT
      studies and directs consideration of methodological variability and child age
      when interpreting study findings.

PMID- 25385306
TI  - Effects of hypothermia combined with neural stem cell transplantation on recovery
      of neurological function in rats with spinal cord injury.
AB  - The microenvironment of the injured spinal cord is hypothesized to be involved in
      driving the differentiation and survival of engrafted neural stem cells (NSCs).
      Hypothermia is known to improve the microenvironment of the injured spinal cord
      in a number of ways. To investigate the effect of NSC transplantation in
      combination with hypothermia on the recovery of rat spinal cord injury, 60
      Sprague-Dawley female rats were used to establish a spinal cord hemisection
      model. They were divided randomly into three groups: A, spinal cord injury group;
      B, NSC transplantation group; and C, NSC transplantation + hypothermia group. At
      1, 2, 4, 6 and 8 weeks post-injury, the motor function of all animals was
      evaluated using the Basso, Beattie and Besnaham locomotor scoring system and the
      inclined plane test. At 4 weeks post-transplantation, histological analysis and
      immunocytochemistry were performed. At 8 weeks post-transplantation, horseradish
      peroxidase nerve tracing and transmission electron microscopy were conducted to
      observe axonal regeneration. The outcome of hind limb motor function recovery in
      group C significantly surpassed that in group B at 4 weeks post-injury (P<0.05).
      Recovery was also observed in group A, but to a lesser degree. For the
      pathological sections no neural axonal were observed in group A. A few axon-like
      structures were observed in group B and more in group C. Horseradish peroxidase
      labeled neurofibers and bromodeoxyuridine-positive cells were observed in the
      spinal cords of group C. Fewer of these cells were found in group B and fewer
      still in group A. The differences among the three groups were significant
      (P<0.05). Using transmission electron microscopy, newly formed nerve fibers and
      myelinated nerve fibers were observed in the central transverse plane in groups B
      and C, although these nerve fibers were not evident in group A. In conclusion,
      NSC transplantation promoted the recovery of hind limb function in rats, and
      combination treatment with hypothermia produced synergistic effects.

PMID- 25385308
TI  - Not quite so fast: effect of training at 90% sprint speed on maximal and repeated
      sprint ability in soccer players.
AB  - Abstract The aim of the present study was to investigate the effect of training
      at an intensity eliciting 90% of maximal sprinting speed on maximal and repeated
      sprint performance in soccer. It was hypothesised that sprint training at 90% of
      maximal velocity would improve soccer-related sprinting. Twenty-two junior club
      level male and female soccer players (age 17 +/- 1 year, body mass 64 +/- 8 kg,
      body height 174 +/- 8 cm) completed an intervention study where the training
      group (TG) replaced one of their weekly soccer training sessions with a repeated
      sprint training session performed at 90% of maximal sprint speed, while the
      control group (CG) completed regular soccer training according to their teams'
      original training plans. Countermovement jump, 12 * 20-m repeated-sprint, VO2max
      and the Yo-Yo Intermittent Recovery Level 1 test were performed prior to and
      after a 9-week intervention period. No significant between-group differences were
      observed for any of the performance indices and effect magnitudes were trivial or
      small. Before rejecting the hypothesis, we recommend that future studies should
      perform intervention programmes with either stronger stimulus or at other times
      during the season where total training load is reduced.

PMID- 25385309
TI  - BAFF regulates follicular helper t cells and affects their accumulation and
      interferon-gamma production in autoimmunity.
AB  - OBJECTIVE: Follicular helper T (Tfh) cells are critical for the development of
      protective antibodies via germinal center (GC) B cell responses; however,
      uncontrolled Tfh cell expansion activates autoreactive B cells to produce
      antibodies that cause autoimmunity. The mechanisms that control Tfh cell
      homeostasis remain largely unknown. The aim of this study was to determine the
      contribution of BAFF to Tfh cell responses in autoimmunity. METHODS: We analyzed
      the properties of Tfh cells in lupus-prone mice sufficient or deficient in BCMA.
      Adoptive transfer studies and mixed bone marrow chimeras were used to test BCMA
      signaling in T cells. We assessed BAFF stimulation of Tfh cells through in vitro
      cell cocultures and in vivo depletion studies using flow cytometry. RESULTS: In
      Nba2 mice, Tfh cells expressed the BAFF receptors BCMA and B lymphocyte
      stimulator receptor 3 (BR-3) and accumulated in the spleen when BCMA was absent.
      BCMA deficiency in T cells promoted the expansion of Tfh cells, GC formation,
      autoantibody production, and interferon-gamma (IFNgamma) production by Tfh cells
      through BR-3. IFNgamma-producing Tfh cells increased BAFF expression in dendritic
      cells. Blocking BAFF or IFNgamma in vivo reduced Tfh cell accumulation and
      reduced autoimmunity in BCMA-deficient animals. Moreover, circulating Tfh-like
      cells that expressed BR-3 (but not BCMA) were elevated in patients with systemic
      lupus erythematosus, and this correlated with serum BAFF and IFNgamma levels.
      CONCLUSION: In Nba2 mice, BCMA negatively regulates Tfh cell expansion, while
      BAFF signaling through BR-3 promotes Tfh cell accumulation. Our findings suggest
      that the balance between BCMA and BR-3 signaling in Tfh cells serves as a
      checkpoint of immune tolerance.

PMID- 25385310
TI  - Cost effectiveness of human papillomavirus-16/18 genotyping in cervical cancer
      screening.
AB  - BACKGROUND: There is limited understanding of the health economic implications of
      cervical screening with human papillomavirus (HPV)-16/18 genotyping. OBJECTIVE:
      The aim of this study was to evaluate the cost effectiveness of cervical cancer
      primary screening with a HPV-16/18 genotyping test which simultaneously detects
      12 other high-risk HPV types. METHODS: A Markov cohort model compared four
      strategies: (1) cytology with reflex HPV testing for atypical squamous cells of
      undetermined significance (ASC-US); (2) co-testing with cytology and HPV testing;
      (3) HPV with reflex to cytology; and (4) HPV with 16/18 genotyping and reflex
      cytology (ASC-US threshold). Screening began at age 30 and was performed
      triennially over 40 years. Screening sensitivity and specificity values for
      cervical intraepithelial neoplasia (CIN) 3 were obtained from the Addressing THE
      Need for Advanced HPV Diagnostics (ATHENA) trial. Outcomes for a 1-year follow-up
      scenario wherein persistent disease was detected were estimated. Screening and
      cancer treatment costs were calculated from a US payer's perspective in 2013.
      Costs and quality-adjusted life-years (QALYs) were discounted at 3 % annually.
      RESULTS: Applying a US$50,000/QALY threshold, strategy (4) dominated strategies
      (2) and (3) by reducing costs and cancer incidence and improving QALYs, and was
      cost effective versus strategy (1). Accounting for persistent >=CIN 3 at 1 year,
      strategy (4) was cost effective versus all other strategies. Detecting HPV-16/18
      resulted in earlier diagnosis of clinically relevant >=CIN 3 at initial screening
      and efficient use of follow-up resources. Outcomes were most influenced by
      strategy performance. CONCLUSIONS: Incorporating HPV-16/18 genotyping is cost
      effective and may improve detection of CIN, thereby preventing cervical cancer.

PMID- 25385311
TI  - Barriers and opportunities in assessing calls to emergency medical communication
      centre--a qualitative study.
AB  - INTRODUCTION: Previous studies have described the difficulties and the complexity
      of assessing an emergency call, and assessment protocols intended to support the
      emergency medical dispatcher's (EMD) assessment have been developed and evaluated
      in recent years. At present, the EMD identifies about 50-70 % of patients
      suffering from cardiac arrest, acute myocardial infarction or stroke. The
      previous research has primarily been focused on specific conditions, and it is
      still unclear whether there are any overall factors that may influence the
      assessment of the call to the emergency medical communication centre (EMCC). AIM:
      The aim of the study was to identify overall factors influencing the registered
      nurses' (RNs) assessment of calls to the EMCC. METHOD: A qualitative study design
      was used; a purposeful selection of calls to the EMCC was analysed by content
      analysis. RESULTS: One hundred calls to the EMCC were analysed. Barriers and
      opportunities related to the RN or the caller were identified as the main factors
      influencing the RN's assessment of calls to the EMCC. The opportunities appeared
      in the callers' symptom description and the communication strategies used by the
      RN. The barriers appeared in callers' descriptions of unclear symptoms, paradoxes
      and the RN's lack of communication strategies during the call. CONCLUSION:
      Barriers in assessing the call to the EMCC were associated with contradictory
      information, the absence of a primary problem, or the structure of the call.
      Opportunities were associated with a clear symptom description that was also
      repeated, and the RN's use of different communication strategies such as closed
      loop communication.

PMID- 25385312
TI  - Wound healing activity of a collagen-derived cryptic peptide.
AB  - Wound healing involves a well-controlled series of interactions among cells and
      several mediators leading to the restoration of damaged tissue. Degradation of
      the extracellular matrix (ECM) protein collagen during remodelling of wound
      tissue leads to the release of bioactive peptides that can possibly influence the
      healing process. The RGD-containing, antioxidative collagen peptide E1 isolated
      in an earlier work was screened in this study for its ability to influence
      multiple steps of the wound healing process. E1 was assayed for and found to be
      chemotactic. Excision and incision wounds were created on separate groups of rats
      and E1 was administered topically. The wound tissues were isolated on the 4th and
      8th days post-wound and subjected to biochemical and biophysical analysis. A
      significant decrease in lipid peroxides in the treatment group confirmed the in
      vivo antioxidant capacity of E1. The treatment group also displayed significant
      increase in total protein, collagen and amino sugar synthesis indicating faster
      ECM formation. The significantly increased rate of wound contraction and
      reepithelialisation along with higher tensile strength of the wound tissue
      corroborated the results of biochemical analysis. The results confirm the
      significant role played by collagen peptides in accelerating the healing process
      and justify their possible use as a pharmaceutical agent. 

PMID- 25385313
TI  - Identification of mitochondrial proteins of malaria parasite using analysis of
      variance.
AB  - As a parasitic protozoan, Plasmodium falciparum (P. falciparum) can cause
      malaria. The mitochondrial proteins of malaria parasite play important roles in
      the discovery of anti-malarial drug targets. Thus, accurate identification of
      mitochondrial proteins of malaria parasite is a key step for understanding their
      functions and finding potential drug targets. In this work, we developed a
      sequence-based method to identify the mitochondrial proteins of malaria parasite.
      At first, we extended adjoining dipeptide composition to g-gap dipeptide
      composition for discretely formulating the protein sequences. Subsequently, the
      analysis of variance (ANOVA) combined with incremental feature selection (IFS)
      was used to pick out the optimal features. Finally, the jackknife cross
      validation was used to evaluate the performance of the proposed model. Evaluation
      results showed that the maximum accuracy of 97.1% could be achieved by using 101
      optimal 5-gap dipeptides. The comparison with previous methods demonstrated that
      our method was accurate and efficient.

PMID- 25385314
TI  - System L amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-L-tyrosine
      (FET).
AB  - O-(2-fluoroethyl)-L-tyrosine (FET) labeled with fluorine-18 is an important and
      specific tracer for diagnostics of glioblastoma via positron emission tomography
      (PET). However, the mechanism of its quite specific accumulation in tumor tissue
      has not been understood so far. In this work we demonstrate that [(3)H]L-tyrosine
      is primarily transported by the system L transporter LAT1 in human LN229
      glioblastoma cells. FET reduced tyrosine transport, suggesting that it shares the
      same uptake pathway. More importantly, accumulation of FET was significantly
      reduced after siRNA-mediated downregulation of LAT1. Xenopus laevis oocytes
      expressing human LAT1 together with the glycoprotein 4F2hc (necessary to pull LAT
      1 to the plasma membrane) exhibited a similar accumulation of FET as observed in
      glioblastoma cells. In contrast, no accumulation was observed in control oocytes,
      not overexpressing an exogenous transporter. Because LAT1 works exclusively as an
      exchanger of amino acids, substrates at one side of the membrane stimulate
      exchange against substrates at the other side. Extracellular FET stimulated the
      efflux of intracellular [(3)H]L-leucine, demonstrating that FET is indeed an
      influx substrate for LAT1. However, FET injected into oocytes was not able to
      stimulate uptake of extracellular [(3)H]L-leucine, indicating that FET is not a
      good efflux substrate. Our data, therefore, suggest that FET is trapped within
      cells due to the asymmetry of its intra- and extracellular recognition by LAT1.
      If also found for other transporters in tumor cells, asymmetric substrate
      recognition may be further exploited for tumor-specific accumulation of PET
      tracers and/or other tumor-related drugs. 

PMID- 25385315
TI  - Effect of mechanical ventilation waveforms on airway wall shear.
AB  - Better understanding of airway wall shear stress/strain rate is very important in
      order to prevent inflammation in patients undergoing mechanical ventilation due
      to respiratory problems in intensive-care medicine. The objective of this study
      was to investigate the role of mechanical ventilation waveforms on airway wall
      shear/strain rate using computational fluid dynamics analysis. Six different
      waveforms were considered to investigate the airway wall shear stress (WSS) from
      fluid dynamics analysis for the airway geometry of two-to-three generations. The
      simulation results showed that Original with Sine Inhale Waveform (OSIW) produced
      the highest WSS value and the Near True Sine Waveform produced the lowest WSS
      value. Also, the Original with Sine Inhale Waveform and the Short Sine Inhale
      with Long Sine Exhale Waveform (SSILSEW) produced a higher shear strain rate in
      comparison to the Original Waveform (OW). These results, combined with
      optimization, suggest that it is possible to develop a set of mechanical
      ventilation waveform strategies to avoid inflammation in the lung.

PMID- 25385316
TI  - Two siblings with homozygous pathogenic splice-site variant in mitochondrial
      asparaginyl-tRNA synthetase (NARS2).
AB  - A homozygous missense mutation (c.822G>C) was found in the gene encoding the
      mitochondrial asparaginyl-tRNA synthetase (NARS2) in two siblings born to
      consanguineous parents. These siblings presented with different phenotypes: one
      had mild intellectual disability and epilepsy in childhood, whereas the other had
      severe myopathy. Biochemical analysis of the oxidative phosphorylation (OXPHOS)
      complexes in both siblings revealed a combined complex I and IV deficiency in
      skeletal muscle. In-gel activity staining after blue native-polyacrylamide gel
      electrophoresis confirmed the decreased activity of complex I and IV, and, in
      addition, showed the presence of complex V subcomplexes. Considering the
      consanguineous descent, homozygosity mapping and whole-exome sequencing were
      combined revealing the presence of one single missense mutation in the shared
      homozygous region. The c.822G>C variant affects the 3' splice site of exon 7,
      leading to skipping of the whole exon 7 and a part of exon 8 in the NARS2 mRNA.
      In EBV-transformed lymphoblasts, a specific decrease in the amount of charged mt
      tRNA(Asn) was demonstrated as compared with controls. This confirmed the
      pathogenic nature of the variant. To conclude, the reported variant in NARS2
      results in a combined OXPHOS complex deficiency involving complex I and IV,
      making NARS2 a new member of disease-associated aaRS2.

PMID- 25385317
TI  - Increased Igf-I/Igfbp-3 Ratios in Postmenopausal Taiwanese with Breast Cancer,
      Irrespective of Er and Pr Statuses and Her2 Expression in a Case-Control Study.
AB  - BACKGROUND: In most research, there were positive associations between the
      insulin-like growth factor I (IGF-I) status, including IGF-I, insulin-like growth
      factor binding protein-3 (IGFBP-3), and ratio of IGF-I/IGFBP-3, and risks of
      breast cancer (BC), which was influenced by many factors, including hormone
      statuses and ethnicity. Therefore, the alterations of the IGF-I status in
      Taiwanese women with BC by menopausal statuses and hormone receptors were
      investigated. METHODS: The levels of IGF-I and IGFBP-3 were determined by the
      enzyme-labeled chemiluminescent immunometric assay, and the protein expression of
      estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth
      factor 2 (HER2) on paraffin-embedded sections of tissues with BC were analyzed by
      the immunohistochemical method. RESULTS: The ratios of IGF-I/IGFBP-3 were
      significantly higher in the women with BC than those in the controls, but not of
      the levels of IGF-I and IGFBP-3; furthermore, the significantly higher ratios
      were found only in the postmenopausal status. In addition, there was no
      significant difference between the IGF-I status and ER and PR statuses, and HER2
      expression, respectively, in the women with BC. CONCLUSIONS: The ratios of IGF
      I/IGFBP-3 were increased in postmenopausal Taiwanese women with BC, irrespective
      of their ages, ER and PR statuses, and HER2 expression.

PMID- 25385318
TI  - Nicotine during pregnancy: changes induced in neurotransmission, which could
      heighten proclivity to addict and induce maladaptive control of attention.
AB  - Prenatal exposure to nicotine, occurring either via maternal smoking or via use
      of transdermal nicotine patches to facilitate cigarette abstinence by pregnant
      women, is associated with ~ 13% of pregnancies worldwide. Nicotine exposure
      during gestation has been correlated with several negative physiological and
      psychosocial outcomes, including heightened risk for aberrant behaviors involving
      alterations in processing of attention as well as an enhanced liability for
      development of drug dependency. Nicotine is a terotogen, altering neuronal
      development of various neurotransmitter systems, and it is likely these
      alterations participate in postnatal deficits in attention control and facilitate
      development of drug addiction. This review discusses the alterations in neuronal
      development within the brain's major neurotransmitter systems, with special
      emphasis placed on alterations within the laterodorsal tegmental nucleus, in
      light of the role this cholinergic nucleus plays in attention and addiction.
      Changes induced within this nucleus by gestational exposure to nicotine, in
      combination with changes induced in other brain regions, are likely to contribute
      to the transgenerational burden imposed by nicotine. Although neuroplastic
      changes induced by nicotine are not likely to act in isolation, and are expected
      to interact with epigenetic changes induced by preconception exposure to drugs of
      abuse, unraveling these changes within the developing brain will facilitate
      eventual development of targeted treatments for the unique vulnerability for
      arousal disorders and development of addiction within the population of
      individuals who have been prenatally exposed to nicotine.

PMID- 25385319
TI  - Participation in church or religious groups and its association with health. Part
      2: a qualitative, Canadian study.
AB  - As part of a mixed-methods study, this qualitative inquiry determined how
      adolescent participation in church or religious groups related to their health.
      We used grounded theory with a phenomenological approach to inquiry. Consistent
      with the quantitative findings, children (n = 12) involved in religious groups
      reported lower participation in risk behaviors, higher pro-social behaviors, but
      poorer levels of emotional well-being and physical health. Findings raise
      theological and practical questions about the practices and teaching of the
      church with respect to children's ministry. They suggest an emphasis on teaching
      about behaviors and morality rather than a more integrative message involving the
      whole of life. 

PMID- 25385320
TI  - Comparative study of indigenously prepared and imported, demineralized, freeze
      dried, irradiated bone allograft in the treatment of periodontal infrabony
      defects.
AB  - Demineralized freeze-dried bone allograft (DFDBA) has been used extensively in
      periodontal therapy. Questions have been raised however, about the osteogenic
      potential of the variety of grafts available. In India the cost factor is another
      important consideration. The aim of this study therefore was to evaluate the
      clinical efficiency of the low priced, indigenously prepared DFDBA obtained from
      the Tata Memorial Hospital (TMH) Tissue Bank, in periodontal regeneration in
      infrabony periodontal defects, as compared to DFDBA obtained from the Pacific
      Coast Tissue Bank (DEMBONE). The latter was used as the control. 16 patients with
      bilaterally similar periodontal infrabony defects were selected, and randomly
      allotted to the test and control groups. At baseline, using standardized
      protocol, recession, probing depths (PD), and clinical attachment levels (CAL)
      were measured, following which periodontal surgery was carried out, with
      placement of the respective graft materials. Patients were recalled after 6
      months for re-assessment. Statistically significant improvement was obtained for
      PD reduction and CAL gain for both groups (p < 0.05). However, no significant
      difference was observed between the test and control groups. It was therefore
      concluded that both the materials from different tissue banks are equally
      effective clinically, with the test material being additionally cost effective.

PMID- 25385321
TI  - Chemical composition and anti-biofilm activity of Thymus sipyleus BOISS. subsp.
      sipyleus BOISS. var. davisianus RONNIGER essential oil.
AB  - In this study, antimicrobial and antibiofilm activities and the chemical
      composition of Thymus sipyleus BOISS. subsp. sipyleus BOISS. var. davisianus
      RONNIGER essential oil was evaluated. The essential oil was obtained by hydro
      distillation and analyzed by gas chromatography-mass spectrometry. Fourteen
      compounds were characterized, having as major components thymol (38.31%) and
      carvacrol (37.95%). Minimum inhibitory concentrations (MICs) of oil and the major
      components were calculated by serial dilution method, and anti-biofilm effects by
      microplate biofilm assay against five Gram positive (Staphylococcus aureus MU 38,
      MU 40, MU 46, MU 47, Stahylococcus epidermidis MU 30) and five Gram negative
      (Pseudomonas aeruginosa MU 187, MU 188, MU 189, Pseudomonas fluorescens MU 180,
      MU 181) bacteria. It was found that MICs for essential oil, thymol and carvacrol
      were between 5 and 50 ul/ml, 0.125-0.5 ug/ml and 0.125-05 ul/ml, respectively.
      The results showed that doses of MIC produced a greater anti-biofilm influence
      than 0.5, 0.25 and 0.125 MIC. In the presence of essential oil (MIC), the mean
      biofilm formation value was equal to 67 +/- 5.5% for P. aeruginosa MU 188, and
      essential oil (MIC) inhibition exceeds 60% for P. aeruginosa biofilms. The
      results also showed that carvacrol (MIC) was able to induce an inhibition 72.9 +/
      4.1% for S.aureus (MU 40) biofilm. In addition, thymol (MIC) showed 68.6 +/-
      5.3% reduction in biofilm formation of P. fluorescens MU 181. This study
      demonstrated the antimicrobial and antibiofilm activity of T. sipyleus BOISS.
      subsp. sipyleus BOISS. var. davisianus RONNIGER essential oil and points out the
      exceptional efficiency of thymol and carvacrol, which could represent candidates
      in the treatment of Pseudomonas and Staphylococcus biofilms.

PMID- 25385323
TI  - Upregulation of Nanog and Sox-2 genes following ectopic expression of Oct-4 in
      amniotic fluid mesenchymal stem cells.
AB  - Octamer-binding transcription factor 4 (Oct-4), an important gene regulating stem
      cell pluripotency, is well-known for its ability to reprogram somatic cells in
      vitro, either alone or in concert with other factors. The aim of this study was
      to assess the effect of ectopic expression of Oct human amniotic fluid stem
      cells. We developed a novel method for isolation of putative human amniotic fluid
      derived multipotent stem cells. These cells showing mesenchymal stem cell
      phenotypes (human amniotic fluid-derived mesenchymal stem cells, hAFMSCs) were
      transfected with a plasmid carrying genes for Oct-4 and the green fluorescent
      protein (GFP). The stably transfected cells, hAFMSCs-Oct4/GFP, were selected by
      using G418 and found to express the GFP reporter gene under the control of Oct-4
      promoter. We found that hAFMSCs developed by our method possess very high self
      renewal ability (about 78 cumulative population doublings) and multilineage
      differentiation potency. Significantly, the hAFMSCs-Oct4/GFP cells showed
      enhanced expression of the three major pluripotency genes Oct-4, Nanog, and Sox
      2, and increased colony-forming ability and growth rate compared with the
      parental hAFMSCs. We demonstrated that the ectopic expression of Oct-4 gene in
      hAFMSCs with high self-renewal ability could upregulate Nanog and Sox-2 gene
      expression and enhance cell growth rate and colony-forming efficiency. Therefore,
      the ectopic expression of Oct-4 could be a strategy to develop pluripotency in
      hAFMSCs for clinical applications. 

PMID- 25385324
TI  - Long-term effects of binary mixtures of 17alpha-ethinyl estradiol and dibutyl
      phthalate in a partial life-cycle test with zebrafish (Danio rerio).
AB  - Using 17alpha-ethinyl estradiol (EE2) and dibutyl phthalate (DBP) as a typical
      estrogen and phthalate ester, respectively, their combined in vivo effects on
      zebrafish (Danio rerio) were investigated from the juvenile state to the adult
      stage. The authors spiked EE2 (5 ng/L and 20 ng/L) and DBP (0.1 mg/L and 0.5
      mg/L) either individually or in mixture. At 45 d postfertilization (dpf), the
      survival rate of zebrafish was comparable in all treatments. Dibutyl phthalate
      did not induce vitellogenin (VTG) synthesis, and no interaction was found between
      EE2 and DBP on VTG induction. At 90 dpf, both liver and gill were subject to more
      severe damage (lipid vacuoles of hepatocytes, amalgamation of gill lamellae, and
      clubbing at the tips of the secondary lamellae) when coexposed to these 2
      chemicals, compared with single exposure. At 115 dpf, generally none of the
      binary mixture groups showed significantly different growth and sex ratios
      compared with the corresponding EE2 alone groups. In conclusion, no obvious
      interactions were detected between EE2 and DBP on the growth, VTG induction, or
      sex ratio of zebrafish, and they may act independently. However, the influence on
      morphology of gonad, liver, and gill induced by exposure to the mixture of EE2
      and DBP was generally more potent than that by single exposure to EE2 or DBP,
      indicating the combined long-term harmful effects of EE2 and DBP on the
      development of zebrafish. Environ Toxicol Chem 2015;34:518-526. (c) 2014 SETAC. 

PMID- 25385322
TI  - Cardiovascular risk factors and future risk of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly
      people, but there are still no curative options. Senile plaques and
      neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular
      pathology is also common. In this review, we summarize findings on cardiovascular
      disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the
      association of clinical CVD (such as stroke and heart disease) and AD. Secondly,
      we summarize the relation between imaging makers of pre-clinical vascular disease
      and AD. Lastly, we discuss the association of cardiovascular risk factors and AD.
      We discuss both established cardiovascular risk factors and emerging putative
      risk factors, which exert their effect partly via CVD. 

PMID- 25385325
TI  - High-resolution genetic maps of Eucalyptus improve Eucalyptus grandis genome
      assembly.
AB  - Genetic maps are key tools in genetic research as they constitute the framework
      for many applications, such as quantitative trait locus analysis, and support the
      assembly of genome sequences. The resequencing of the two parents of a cross
      between Eucalyptus urophylla and Eucalyptus grandis was used to design a single
      nucleotide polymorphism (SNP) array of 6000 markers evenly distributed along the
      E. grandis genome. The genotyping of 1025 offspring enabled the construction of
      two high-resolution genetic maps containing 1832 and 1773 markers with an average
      marker interval of 0.45 and 0.5 cM for E. grandis and E. urophylla, respectively.
      The comparison between genetic maps and the reference genome highlighted 85% of
      collinear regions. A total of 43 noncollinear regions and 13 nonsynthetic regions
      were detected and corrected in the new genome assembly. This improved version
      contains 4943 scaffolds totalling 691.3 Mb of which 88.6% were captured by the 11
      chromosomes. The mapping data were also used to investigate the effect of
      population size and number of markers on linkage mapping accuracy. This study
      provides the most reliable linkage maps for Eucalyptus and version 2.0 of the E.
      grandis genome.

PMID- 25385326
TI  - Complement C5-deficient mice are protected from seizures in experimental cerebral
      malaria.
AB  - Studies have demonstrated that the membrane attack complex (MAC) of complement
      can evoke seizures when injected directly into rodent brain. In the course of
      studies that examine the role of complement in the development of experimental
      cerebral malaria (ECM), we observed fewer seizures in mice deficient in C5, a
      component required for MAC formation. To determine if the MAC contributed to the
      tonic-clonic seizures characteristic of ECM, we performed long-term video
      electroencephalography (EEG) on C5(-/-) mice with Plasmodium berghei ANKA-induced
      cerebral malaria and observed significantly reduced spike and seizure frequency
      compared to wild-type mice. Our data suggest a role for the MAC in malaria
      induced seizures and that inhibition of the terminal complement pathway may
      reduce seizures and seizure-related neurocognitive deficits. 

PMID- 25385328
TI  - Expression and functional role of Nav1.9 sodium channel in cartwheel cells of the
      dorsal cochlear nucleus.
AB  - In the central auditory system, cartwheel cells (CWCs) are a group of
      interneurons in the dorsal cochlear nucleus (DCN). While other DCN neurons
      respond to stimuli with a simple discharge pattern of single action potentials
      (SAPs), CWCs respond with complex action potentials (CAPs), consisting of SAPs
      superimposed on a slow depolarization. The CAPs in CWCs may participate in
      various auditory or non-auditory signaling processing but its intrinsic
      mechanisms are largely unknown. In the present study, in vitro whole-cell current
      clamp recordings on neonatal mice brain slices were used to demonstrate that CWCs
      respond to brief voltage stimulation with CAPs. Western blotting and
      immunohistochemistry were also utilized to demonstrate that Nav1.9 was expressed
      in the CWCs. Finally, when Nav1.9 was genetically silenced, CWCs responded to
      voltage stimulation with SAPs, not CAPs. The results strongly suggested that
      Nav1.9 was expressed and functionally contributed to the signaling processing in
      the central auditory pathway.

PMID- 25385329
TI  - A highly stable zeotype mesoporous zirconium metal-organic framework with
      ultralarge pores.
AB  - Through topological rationalization, a zeotype mesoporous Zr-containing metal
      organic framework (MOF), namely PCN-777, has been designed and synthesized. PCN
      777 exhibits the largest cage size of 3.8 nm and the highest pore volume of 2.8
      cm(3)  g(-1) among reported Zr-MOFs. Moreover, PCN-777 shows excellent stability
      in aqueous environments, which makes it an ideal candidate as a support to
      incorporate different functional moieties. Through facile internal surface
      modification, the interaction between PCN-777 and different guests can be varied
      to realize efficient immobilization. 

PMID- 25385327
TI  - Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma.
AB  - Malignant melanoma is associated with poor clinical prognosis; however, novel
      molecular and immune therapies are now improving patient outcomes. Almost 50% of
      melanomas harbor targetable activating mutations of BRAF that promote RAS-RAF-MEK
      ERK pathway activation and melanoma proliferation. Recent evidence also indicates
      that melanomas bearing mutant BRAF may also have altered immune responses,
      suggesting additional avenues for treatment of this patient group. The small
      molecule inhibitors selective for mutant BRAF induce significant but short-lived
      clinical responses in a proportion of patients, but also lead to immune
      stimulatory bystander events, which then subside with the emergence of resistance
      to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination
      of BRAF inhibitors with new immunotherapies such as checkpoint blockade
      antibodies, may further enhance immune activation, or counteract
      immunosuppressive signals. Preclinical evaluation and ongoing clinical trials
      should provide novel insights into the role of immunity in the therapy of BRAF
      mutant melanoma.

PMID- 25385330
TI  - Antisense oligonucleotide therapies: the promise and the challenges from a
      toxicologic pathologist's perspective.
AB  - Many antisense oligonucleotides (ASOs) from several classes of molecules are
      currently in drug development. Despite over 20 years of pharmaceutical research,
      few ASOs have been marketed due to problems with clinical efficacy or preclinical
      toxicologic challenges. However, a number of recent developments have renewed
      interest in this class including the registration of mipomersen, the advent of
      successful screening strategies to eliminate more toxic molecules, and new
      understanding of the risks of off-target nucleotide binding and mitigation of
      potential off-target effects. Recent advances in backbone chemistries,
      conjugation to other moieties, and new delivery systems have allowed better
      tissue penetration, enhanced intracellular targeting, and less frequent dosing,
      resulting in fewer toxicities. While these new developments provide invigorated
      interest in these platforms, a few lingering challenges and preclinical/clinical
      toxicity issues remain to be completely resolved, including: (1) proinflammatory
      effects (vasculitis/inflammatory infiltrates); (2) nephrotoxicity and
      hepatotoxicity unrelated to lysosomal accumulation; and (3) thrombocytopenia.
      Recent investigative work by several laboratories have helped elucidate
      mechanisms for these issues, allowing a better understanding of the clinical
      relevance and implications of particular toxicities. It is important for
      toxicologists, pathologists, and regulatory reviewers to be familiar with new
      developments in the ASO field and their implications, as a greater number of new
      types of antisense molecules undergo preclinical toxicity testing. 

PMID- 25385332
TI  - Stride frequency and length adjustment in post-stroke individuals: influence on
      the margins of stability.
AB  - OBJECTIVE: To investigate whether post-stroke participants can walk at different
      combinations of stride frequency and stride length and how these adaptations
      affect the backward and medio-lateral margins of stability. SETTING: Computer
      Assisted Rehabilitation Environment (CAREN). PARTICIPANTS: Ten post-stroke
      individuals. INTERVENTION: Six trials of 2 min walking on a treadmill at
      different combinations of stride frequency and stride length. Treadmill speed was
      set at the corresponding speed, and subjects received visual feedback about the
      required and actual stride length. OUTCOME MEASURES: Mean stride length and
      frequency and backward and medio-lateral margins of stability for each trial.
      RESULTS AND CONCLUSION: Stroke patients were able to adjust step length when
      required, but had difficulty adjusting step frequency. When a stride frequency
      higher than self-selected stride frequency was imposed patients additionally
      needed to increase stride length in order to match the imposed treadmill speed.
      For trials at a high stride frequency, in particular, the increase in the
      backward and medio-lateral margins of stability was limited. In conclusion,
      training post-stroke individuals to increase stride frequency during walking
      might give them more opportunities to increase the margins of stability and
      consequently reduce fall risk.

PMID- 25385331
TI  - Proceedings of the 2014 National Toxicology Program Satellite Symposium.
AB  - The 2014 annual National Toxicology Program (NTP) Satellite Symposium, entitled
      "Pathology Potpourri" was held in Washington, D.C., in advance of the Society of
      Toxicologic Pathology's 33rd annual meeting. The goal of this annual NTP
      Symposium is to present current diagnostic pathology or nomenclature issues to
      the toxicologic pathology community. This article presents summaries of the
      speakers' presentations, including diagnostic or nomenclature issues that were
      presented, along with select images that were used for audience voting and
      discussion. Some lesions and topics covered during the symposium included a
      pulmonary mucinous adenocarcinoma in a male B6C3F1 mouse; plexiform vasculopathy
      in Wistar Han (Crl:WI[Han]) rats; staging of the estrous cycle in rats and mice;
      peri-islet fibrosis, hemorrhage, lobular atrophy and inflammation in male Sprague
      Dawley (SD) rats; retinal dysplasia in Crl:WI[Han] rats and B6C3F1 mice;
      multicentric lymphoma with intravascular microemboli and tumor lysis syndrome,
      and 2 cases of myopathy and vascular anomaly in Tg.rasH2 mice; benign thymomas in
      Crl:WI[Han] rats; angiomatous lesions in the mesenteric lymph nodes of
      Crl:WI[Han] rats; an unusual foveal lesion in a cynomolgous monkey; and finally a
      series of nomenclatures challenges from the endocrine International Harmonization
      of Nomenclature and Diagnostic Criteria (INHAND) Organ Working Group (OWG). 

PMID- 25385333
TI  - Analysis of effectiveness of R1-nj anthocyanin marker for in vivo haploid
      identification in maize and molecular markers for predicting the inhibition of R1
      nj expression.
AB  - KEY MESSAGE: R1-nj anthocyanin marker inhibition is highly frequent in tropical
      maize germplasm considerably affecting efficiency of haploid identification.
      Molecular markers reliably differentiating germplasm with anthocyanin color
      inhibitor have been identified in this study. The R1-Navajo (R1-nj) color marker
      facilitates easy and quick identification of haploid kernels at the seed stage
      during in vivo haploid induction process in maize. However, the Navajo phenotype
      can be completely suppressed or poorly expressed in some germplasm, making it
      impossible or inefficient to identify haploids at the seed stage. In this study,
      we characterized the expression of R1-nj marker in a large array of
      tropical/subtropical inbred lines, breeding populations and landraces by crossing
      with the R1-nj-based tropicalized haploid inducer. There was a high frequency of
      inhibition of the Navajo phenotype in the maize inbred lines, which are used in
      tropical breeding programs. Genome-wide association mapping showed that the C1
      anthocyanin regulatory locus is the most significant genetic factor influencing
      inhibition of the Navajo phenotype. Molecular marker assays were designed based
      on polymorphism in the C1 vs C1-I alleles. Analysis of a set of 714 inbred lines
      demonstrated that a combination of two gene-specific markers--8 bp C1-I InDel and
      C1-I SNP--could predict with high accuracy the presence of anthocyanin color
      inhibition in the germplasm analyzed. Information generated in this study aids in
      making informed decisions on the constitution of source populations for doubled
      haploid (DH) line development in tropical germplasm, particularly those derived
      from elite maize lines from CIMMYT. The C1-I gene-specific molecular markers
      identified and validated will facilitate high-throughput and cost-effective
      evaluation of a large pool of germplasm for the presence of the dominant color
      inhibitor in maize germplasm.

PMID- 25385335
TI  - Stroke: improved lesion-symptom mapping in poststroke aphasia.

PMID- 25385336
TI  - Neuroimmunology: towards more-accurate diagnosis in neuromyelitis optica.
AB  - Neuromyelitis optica spectrum disorders (NMOSD) can mimic multiple sclerosis
      (MS). Avoiding misdiagnosis is crucial, because some disease-modifying drugs for
      MS can aggravate NMOSD, causing blindness and paraplegia. A recent study reports
      that misdiagnosis of NMOSD as MS occasionally occurs, and that a two-step
      antibody assay could improve differential diagnosis.

PMID- 25385334
TI  - Neuroimaging in Parkinson disease: from research setting to clinical practice.
AB  - Over the past three decades, neuroimaging studies-including structural,
      functional and molecular modalities-have provided invaluable insights into the
      mechanisms underlying Parkinson disease (PD). Observations from multimodal
      neuroimaging techniques have indicated changes in brain structure and metabolic
      activity, and an array of neurochemical changes that affect receptor sites and
      neurotransmitter systems. Characterization of the neurobiological alterations
      that lead to phenotypic heterogeneity in patients with PD has considerably aided
      the in vivo investigation of aetiology and pathophysiology, and the
      identification of novel targets for pharmacological or surgical treatments,
      including cell therapy. Although PD is now considered to be very complex, no
      neuroimaging modalities are specifically recommended for routine use in clinical
      practice. However, conventional MRI and dopamine transporter imaging are commonly
      used as adjuvant tools in the differential diagnosis between PD and
      nondegenerative causes of parkinsonism. First-line neuroimaging tools that could
      have an impact on patient prognosis and treatment strategies remain elusive. This
      Review discusses the lessons learnt from decades of neuroimaging research in PD,
      and the promising new approaches with potential applicability to clinical
      practice. 

PMID- 25385338
TI  - Demyelinating disease: new study refutes link between vaccines and demyelination.

PMID- 25385337
TI  - Microglial and macrophage polarization-new prospects for brain repair.
AB  - The traditional view of the adult brain as a static organ has changed in the past
      three decades, with the emergence of evidence that it remains plastic and has
      some regenerative capacity after injury. In the injured brain, microglia and
      macrophages clear cellular debris and orchestrate neuronal restorative processes.
      However, activation of these cells can also hinder CNS repair and expand tissue
      damage. Polarization of macrophage populations toward different phenotypes at
      different stages of injury might account for this dual role. This Perspectives
      article highlights the specific roles of polarized microglial and macrophage
      populations in CNS repair after acute injury, and argues that therapeutic
      approaches targeting cerebral inflammation should shift from broad suppression of
      microglia and macrophages towards subtle adjustment of the balance between their
      phenotypes. Breakthroughs in the identification of regulatory molecules that
      control these phenotypic shifts could ultimately accelerate research towards
      curing brain disorders.

PMID- 25385340
TI  - Current and future burden of incident hip fractures in New South Wales,
      Australia.
AB  - Population ageing presents significant challenges for many developed nations.
      Accurately forecasting the likely future burden of age-related medical
      conditions, such as hip fracture, is critical. In this study, we present
      estimates of the current and future burden of hip fracture in NSW, Australia,
      providing crucial information for future health care planning. PURPOSE: The aims
      of this study were to investigate the burden of hip fracture in Australia's
      largest state, New South Wales (NSW), and to build a prediction model to forecast
      the likely future burden of hip fracture from 2016 to 2036 in persons aged 50
      years or more. METHODS: A retrospective population-based cohort study was
      conducted using NSW hospitalisation data. Standardised incident hip fracture
      rates and hip fracture-related acute care length of stay and costs were
      estimated. Predictive negative binomial regression modelling using age, gender
      and local health district and year covariates together with projected NSW
      populations was applied to forecast future hip fractures. RESULTS: Total incident
      hip fractures increased 8.8 % over a 12-year period from 2000/2001 to 2011/2012
      despite declining age-standardised rates. Estimates of acute care length of stay
      for the treatment of hip fracture ranged from 10 to 15 days and acute care costs
      ranged between 21 and 29,000 Australian dollars per fracture. By 2036, incident
      hip fractures are projected to rise by 35.2 %, assuming a continued decline in
      the rate of hip fracture or by 107.5 % if the current decline in the rate does
      not continue. Acute care length of stay and costs are each predicted to rise
      between 37.1 and 110.4 % by 2036. CONCLUSION: An ageing population and changing
      demographics will continue to drive the increasing burden of incident hip
      fractures in NSW and Australia in the foreseeable future. These anticipated
      changes provide important information for the planning and management of future
      hip fracture care.

PMID- 25385341
TI  - Human induced pluripotent stem cell-derived hepatocytes for toxicology testing.
AB  - The need for more predictive in vitro toxicity models is a critical deficit in
      current preclinical pipeline safety evaluations. Current models employing tumor
      derived cancer cell lines and isolated primary human hepatocytes (PHHs) afford an
      approximation of overt cytotoxicity but do not provide hepatotoxicity prediction
      owing to liabilities in metabolic activity along with phenotypic variability and
      instability in culture. Induced pluripotent stem cell-derived hepatocytes (iPSC
      HCs) offer a long-term solution to accessing liver tissue from representative
      diverse as well as idiosyncratic patient populations and can be sourced
      indefinitely. iPSC-HCs are currently being evaluated as potential replacements
      for the existing cell models, but they have yet to prove superiority. It is
      acknowledged that iPSC-HCs are not functionally equivalent to PHHs and are
      somewhat mixed in terms of their gene expression profile, simultaneously
      displaying mature and immature markers in vitro. Combining iPSC-HCs with
      organotypic culture systems affords an opportunity to maximize the potential of
      both technologies where the cells benefit from more complex culture conditions
      while unlocking the potential of the culture systems by affording stability and
      reproducibility to provide the future of predictive in vitro toxicity models. 

PMID- 25385343
TI  - Construction of a lncRNA-PCG bipartite network and identification of cancer
      related lncRNAs: a case study in prostate cancer.
AB  - LncRNAs are involved in a wide range of biological processes, such as chromatin
      remodeling, mRNA splicing, mRNA editing and translation. They can either
      upregulate or downregulate gene expression, and play key roles in the progression
      of various human cancers. However, the functional mechanisms of most lncRNAs
      still remain unknown at present. This paper aims to provide space for the
      understanding of lncRNAs by proposing a new method to obtain protein-coding genes
      (PCGs) regulated by lncRNAs, thus identifying candidate cancer-related lncRNAs
      using bioinformatics approaches. This study presents a method based on sample
      correlation, which is applied to the expression profiles of lncRNAs and PCGs in
      prostate cancer in combination with protein interaction data to build a lncRNA
      PCG bipartite network. Candidate cancer-related lncRNAs were extracted from the
      bipartite network by using a random walk. 14 prostate cancer-related lncRNAs were
      acquired from the LncRNADisease database and MNDR, of which 6 lncRNAs were
      present in our network. As one of the seed nodes, ENSG00000234741 achieved the
      highest score among them. The other two cancer-related lncRNAs (ENSG00000225937
      and ENSG00000236830) were ranked within the top 30. In addition, the top
      candidate lncRNA ENSG00000261777 shares an intron with DDX19, and interacts with
      IGF2 P1, indicating its involvement in prostate cancer. In this paper, we
      described a new method for predicting candidate lncRNA targets, and obtained
      candidate therapeutic targets using this method. We hope that this study will
      bring a new perspective in future lncRNA studies. 

PMID- 25385339
TI  - 'The clocks that time us'--circadian rhythms in neurodegenerative disorders.
AB  - Circadian rhythms are physiological and behavioural cycles generated by an
      endogenous biological clock, the suprachiasmatic nucleus. The circadian system
      influences the majority of physiological processes, including sleep-wake
      homeostasis. Impaired sleep and alertness are common symptoms of
      neurodegenerative disorders, and circadian dysfunction might exacerbate the
      disease process. The pathophysiology of sleep-wake disturbances in these
      disorders remains largely unknown, and is presumably multifactorial. Circadian
      rhythm dysfunction is often observed in patients with Alzheimer disease, in whom
      it has a major impact on quality of life and represents one of the most important
      factors leading to institutionalization of patients. Similarly, sleep and
      circadian problems represent common nonmotor features of Parkinson disease and
      Huntington disease. Clinical studies and experiments in animal models of
      neurodegenerative disorders have revealed the progressive nature of circadian
      dysfunction throughout the course of neurodegeneration, and suggest strategies
      for the restoration of circadian rhythmicity involving behavioural and
      pharmacological interventions that target the sleep-wake cycle. In this Review,
      we discuss the role of the circadian system in the regulation of the sleep-wake
      cycle, and outline the implications of disrupted circadian timekeeping in
      neurodegenerative diseases. 

PMID- 25385344
TI  - MRI characteristics of fourth ventricle arachnoid diverticula in five dogs.
AB  - Intracranial arachnoid diverticula (cysts) are rare accumulations of
      cerebrospinal fluid (CSF) within the arachnoid membrane. The purpose of this
      retrospective study was to describe magnetic resonance imaging (MRI)
      characteristics of fourth ventricle arachnoid diverticula in a group of dogs. The
      hospital's medical records were searched for dogs with MRI studies of the brain
      and a diagnosis of fourth ventricle arachnoid diverticulum. Clinical
      characteristics were recorded from medical records and MRI studies were
      reinterpreted by a board-certified veterinary radiologist. Five pediatric dogs
      fulfilled inclusion criteria. Clinical signs included cervical hyperaesthesia,
      obtundation, tetraparesis, and/or central vestibular syndrome. In all five dogs,
      MRI findings were consistent with obstructive hydrocephalus, based on dilation of
      all ventricles and compression of the cerebellum and brainstem. All five dogs
      also had cervical syringohydromyelia, with T2-weighted hyperintensity of the gray
      matter of the cord adjacent to the syringohydromyelia. A signal void, interpreted
      as flow disturbance, was observed at the mesencephalic aqueduct in all dogs. Four
      dogs underwent surgical treatment with occipitalectomy and durotomy. A cystic
      lesion emerging from the fourth ventricle was detected in all four dogs during
      surgery and histopathology confirmed the diagnosis of arachnoid diverticula.
      Three dogs made excellent recovery but deteriorated shortly after surgery and
      were euthanized. Repeat MRI in two dogs revealed improved hydrocephalus but
      worsening of the syringohydromyelia. Findings from the current study supported
      theories that fourth ventricle arachnoid diverticula are secondary to partial
      obstruction of the central canal or lateral apertures and that arachnoid
      diverticula are developmental lesions in dogs. 

PMID- 25385346
TI  - Incidence of defibrillator shocks after elective generator exchange following
      uneventful first battery life.
AB  - BACKGROUND: A significant number of implantable cardioverter-defibrillator (ICD)
      patients do not experience shocks after ICD implant. Elective generator exchange
      (GE) has been associated with increased risk of infection and ICD lead failure.
      There is a paucity of contemporary data reporting on shock incidence with
      replacement devices. METHODS AND RESULTS: Patients undergoing elective GE (n=24
      203) who transmit data remotely via a remote monitoring system were analyzed to
      determine the incidence of ICD shocks after GE. A total of 16 230 patients (67%)
      did not experience a shock with the first ICD (group A), and 7973 (33%) received
      at least 1 shock (group B). Patients in group A were older (71.3 versus 68.8
      years, P<0.001) and more often female (71% versus 77% male, P<0.001). Over an
      average follow-up of 1.9+/-1.2 years after GE, the proportion of patients with
      shocks and risk of ICD shocks was lower for those who did not receive a shock
      during the first battery life (group A: 9.9% versus 27.7%, hazard ratio 0.36, 95%
      CI 0.34 to 0.38, P<0.001). The cumulative rate of ICD shocks at 5 years after GE
      was 25.7% in group A and 51.1% in group B. CONCLUSIONS: In this large cohort of
      ICD patients implanted across the United States, two thirds did not receive ICD
      shock therapy prior to GE. The occurrence of ICD shocks prior to GE is an
      important predictor of shocks after GE; however, even among those without shocks
      during first battery life, the incidence of shocks at 5 years following GE is
      >25%. These data should support informed decision making for patients and
      physicians at the time of ICD generator end of service.

PMID- 25385347
TI  - Readiness for practice: a survey of neurosurgery graduates and program directors.
AB  - BACKGROUND: Postgraduate neurosurgical education is undergoing significant
      reform, including transition to a competency-based training model. To support
      these efforts, the purpose of this study was to determine neurosurgical
      graduates' and program directors' (PDs) opinions about graduates' level of
      competence in reference to the 2010 Royal College Objectives of Training in
      Neurosurgery. METHODS: An electronic survey was distributed to Canadian
      neurosurgery PDs and graduates from 2011. The questionnaire addressed graduates'
      abilities in nonprocedural knowledge and skills, CanMEDS roles, proficiency with
      core neurosurgical procedures and knowledge of complex neurosurgical techniques.
      RESULTS: Thirteen of 22 (59%) graduate and 17/25 (65%) PD surveys were completed.
      There were no significant differences between PD and graduate responses. Most
      respondents agreed that these graduates possess the knowledge and skills expected
      of an independently practicing neurosurgeon across current objectives of
      training. A small proportion felt some graduates did not achieve this level of
      proficiency on specific vascular, functional, peripheral nerve and endoscopic
      procedures. This was partially attributed to limited exposure to these procedures
      during training and perceptions that some techniques required fellowship-level
      training. CONCLUSIONS: Graduating neurosurgical residents are perceived to
      possess a high level of proficiency in the majority of neurosurgical practice
      domains. Inadequate exposure during training or a perception that subspecialists
      should perform some procedures may contribute to cases where proficiency is not
      as high. The trends identified in this study could be monitored on an ongoing
      basis to provide supplemental data to guide curricular decisions in Canadian
      neurosurgical training.

PMID- 25385345
TI  - Large-scale gene-centric analysis identifies polymorphisms for resistant
      hypertension.
AB  - BACKGROUND: Resistant hypertension (RHTN), defined by lack of blood pressure (BP)
      control despite treatment with at least 3 antihypertensive drugs, increases
      cardiovascular risk compared with controlled hypertension. Yet, there are few
      data on genetic variants associated with RHTN. METHODS AND RESULTS: We used a
      gene-centric array containing ~50 000 single-nucleotide polymorphisms (SNPs) to
      identify polymorphisms associated with RHTN in hypertensive participants with
      coronary artery disease (CAD) from INVEST-GENES (the INnternational VErapamil-SR
      Trandolapril STudy-GENEtic Substudy). RHTN was defined as BP>=140/90 on 3 drugs,
      or any BP on 4 or more drugs. Logistic regression analysis was performed in
      European Americans (n=904) and Hispanics (n=837), using an additive model
      adjusted for age, gender, randomized treatment assignment, body mass index,
      principal components for ancestry, and other significant predictors of RHTN.
      Replication of the top SNP was conducted in 241 European American women from WISE
      (Women's Ischemia Syndrome Evaluation), where RHTN was defined similarly. To
      investigate the functional effect of rs12817819, mRNA expression was measured in
      whole blood. We found ATP2B1 rs12817819 associated with RHTN in both INVEST
      European Americans (P-value=2.44*10(-3), odds ratio=1.57 [1.17 to 2.01]) and
      INVEST Hispanics (P=7.69*10(-4), odds ratio=1.76 [1.27 to 2.44]). A consistent
      trend was observed at rs12817819 in WISE, and the INVEST-WISE meta-analysis
      result reached chip-wide significance (P=1.60*10(-6), odds ratio=1.65 [1.36 to
      1.95]). Expression analyses revealed significant differences in ATP2B1 expression
      by rs12817819 genotype. CONCLUSIONS: The ATP2B1 rs12817819 A allele is associated
      with increased risk for RHTN in hypertensive participants with documented CAD or
      suspected ischemic heart disease. CLINICAL TRIAL REGISTRATION URL:
      www.clinicaltrials.gov; Unique identifiers: NCT00133692 (INVEST), NCT00000554
      (WISE).

PMID- 25385348
TI  - Computational image analysis of colony and nuclear morphology to evaluate human
      induced pluripotent stem cells.
AB  - Non-invasive evaluation of cell reprogramming by advanced image analysis is
      required to maintain the quality of cells intended for regenerative medicine.
      Here, we constructed living and unlabelled colony image libraries of various
      human induced pluripotent stem cell (iPSC) lines for supervised machine learning
      pattern recognition to accurately distinguish bona fide iPSCs from improperly
      reprogrammed cells. Furthermore, we found that image features for efficient
      discrimination reside in cellular components. In fact, extensive analysis of
      nuclear morphologies revealed dynamic and characteristic signatures, including
      the linear form of the promyelocytic leukaemia (PML)-defined structure in iPSCs,
      which was reversed to a regular sphere upon differentiation. Our data revealed
      that iPSCs have a markedly different overall nuclear architecture that may
      contribute to highly accurate discrimination based on the cell reprogramming
      status. 

PMID- 25385349
TI  - Malignant melanoma of the penis and urethra: one case report.
AB  - We present a case of a patient with malignant melanoma of the glans penis and
      urethra, which was found in a 53-year-old man with nonhealing ulcerative penile
      lesion and bilateral, clinically palpable inguinal lymphadenopathies at
      diagnosis. A diagnostic biopsy showed the characteristics of a melanoma. We
      treated the patient with total penectomy and bilateral inguinal lymph node
      dissection. After surgery, chemotherapy with bleomycin, vincristine and cisplatin
      and immunotherapy with thymosin injection were started. No recurrence or
      metastasis occurred during the 3 years after the operation. Melanoma of the penis
      is very rare, and early diagnosis is important because the patient prognosis is
      very poor. 

PMID- 25385350
TI  - Aortic stenosis: flow matters.

PMID- 25385351
TI  - Soybean chalcone isomerase: evolution of the fold, and the differential
      expression and localization of the gene family.
AB  - MAIN CONCLUSION: Soybean chalcone isomerase (CHI) family contains twelve members
      with unique evolutionary background, expression patterns and is compartmentalized
      to specific subcellular locations. The phenylpropanoid pathway produces a diverse
      array of plant natural products. A key branch-point enzyme, chalcone isomerase,
      catalyzes the reaction producing flavanones, the backbone for many downstream
      metabolites such as flavonoids and isoflavonoids. We have identified twelve
      soybean GmCHIs that fall into four subfamilies. The study of this family in
      soybean in the context of various CHIs and CHI-like proteins, across divisions in
      the plant kingdom and beyond, shows an evolutionary journey from fatty acid
      binding proteins (FAPs) to sterically restricted folds that gave rise to the
      chalcone-to-flavanone isomerase. There are four GmCHIs with this functionality,
      three of which belong to a legume-specific clade known as 'type II' CHIs. Tissue
      specific expression of eight core members of the soybean CHI family showed
      differential temporal and spatial expression, pointing to the potential function
      of GmCHI1A in seed isoflavonoid production. Promoter analysis of the GmCHIs
      described the minutiae of sub-organ expression patterns. Subcellular localization
      of the family was conducted to investigate the possibility of pathway-specific
      compartmentalization. Subfamilies 1, 2 and 4 localized to the nucleus and
      cytoplasm, with nuclear localization of CHIs raising questions about alternate
      function. GmCHI3 isoforms localized to the chloroplast, which, in conjunction
      with their position on the phylogenetic tree and expression patterns, closely
      associates them with the FAPs. This study provides the first comprehensive look
      at soybean CHIs, a family of unique evolutionary background and biochemical
      function, with the catalytically active members producing the backbone substrate
      in an important plant metabolic pathway.

PMID- 25385352
TI  - Concerns over use of hydroxyethyl starch solutions.

PMID- 25385353
TI  - Incorporating three-dimensional printing into a simulation-based congenital heart
      disease and critical care training curriculum for resident physicians.
AB  - OBJECTIVE: Although simulation-based education is now commonly utilized in
      medicine, its use in the instruction of congenital heart disease remains limited.
      The objective of this study is to evaluate whether heart models created with
      three-dimensional printing technology can be effectively incorporated into a
      simulation-based congenital heart disease and critical care training curriculum
      for pediatric resident physicians. DESIGN: Utilizing heart models created with a
      three-dimensional printer, pediatric residents participated in a 60-minute
      simulation seminar with three consecutive components: (1) didactic instruction on
      ventricular septal defect anatomy; (2) didactic/simulation-based instruction on
      echocardiographic imaging of ventricular septal defects and anatomical
      teaching/operative simulation of ventricular septal defect repair; (3) simulation
      based instruction on postoperative critical care management of ventricular septal
      defects. SETTING: Academic, free-standing, children's hospital with quaternary
      care referrals. PARTICIPANTS: Twenty-three pediatric resident physicians. OUTCOME
      MEASURES: Subjective, Likert-type questionnaires assessing knowledge acquisition,
      knowledge reporting, and structural conceptualization of ventricular septal
      defects. RESULTS: Three-dimensional printing technology was successfully utilized
      to create heart models of five common ventricular septal defect subtypes. After
      using these models in a simulation-based curriculum, pediatric residents were
      found to have improvement in the areas of knowledge acquisition (P = .0082),
      knowledge reporting (P = .01), and structural conceptualization (P < .0001) of
      ventricular septal defects, as well as improvement in the ability to describe and
      manage postoperative complications in ventricular septal defect patients in the
      critical care setting. CONCLUSIONS: The utilization of three-dimensional printing
      in a simulation-based congenital heart disease and critical care training
      curriculum is feasible and improves pediatric resident physicians' understanding
      of a common congenital heart abnormality.

PMID- 25385354
TI  - Acroosteolysis presenting with brachyonychia following exposure to cold.
AB  - BACKGROUND: A vast number of conditions ranging from simple trauma to hereditary
      and collagen vascular disease had been described in association with
      acroosteolysis. OBJECTIVE: To demonstrate that severe cold exposure not mounting
      to frostbite may be associated with acroosteolysis. METHODS: A 16-year-old girl
      with acroosteolysis presenting with brachyonychia was fully investigated for
      possible cause of her nail and bone deformity. RESULTS: Lab investigations
      including Parathormone levels, Anti Scl 70, ANA, Anti-CCP and RF levels were all
      normal. X-ray imaging revealed resorption of the tufts of the terminal phalanges
      bilaterally. Disruption of nail fold capillaries with sluggish flow in capillary
      loops was evident on capillaroscopy. CONCLUSION: It had been repeatedly reported
      that frostbite, Raynaud's disease and diseases associated with repeated
      chilblains may be associated with secondary cold-induced acroosteolysis. Here, we
      present a case of acroosteolysis associated with brachyonychia following exposure
      to severe cold not mounting to frostbite.

PMID- 25385355
TI  - siGnum: graphical user interface for EMG signal analysis.
AB  - Electromyography (EMG) signals that represent the electrical activity of muscles
      can be used for various clinical and biomedical applications. These are
      complicated and highly varying signals that are dependent on anatomical location
      and physiological properties of the muscles. EMG signals acquired from the
      muscles require advanced methods for detection, decomposition and processing.
      This paper proposes a novel Graphical User Interface (GUI) siGnum developed in
      MATLAB that will apply efficient and effective techniques on processing of the
      raw EMG signals and decompose it in a simpler manner. It could be used
      independent of MATLAB software by employing a deploy tool. This would enable
      researcher's to gain good understanding of EMG signal and its analysis procedures
      that can be utilized for more powerful, flexible and efficient applications in
      near future.

PMID- 25385356
TI  - A new lipase as a pharmaceutical target for battling infections caused by
      Staphylococcus aureus: Gene cloning and biochemical characterization.
AB  - Staphylococcus aureus lipases along with other cell-wall-associated proteins and
      enzymes (i.e., catalase, coagulase, protease, hyaluronidase, and beta-lactamase)
      play important roles in the pathogenesis of S. aureus and are important subject
      of drug targeting. The appearance of antibiotic-resistant types of pathogenic S.
      aureus (e.g., methicillin-resistant S. aureus, MRSA) is a worldwide medical
      problem. In the present work, a novel lipase from a newly isolated MRSA strain
      from a cow with subclinical mastitis was cloned and biochemically characterized.
      The mature part of the lipase was expressed in Escherichia coli and purified by
      nickel affinity chromatography. It displays a high lipase activity at pH 8.0 and
      25  degrees C using p-nitrophenyl palmitate and has a preference for medium-long
      chain substrates of p-nitrophenyl esters (pNPC10-C16). Furthermore, in search of
      inhibitors, the effect of farnesol on the growth of S. aureus and the lipase
      activity was also studied. Farnesol inhibits the growth of S. aureus and is a
      mixed-type inhibitor with Ki and Ki (') values of 0.2 and 1.2 mmol L(-1),
      respectively. A lipase with known properties could not only serve as a template
      for developing inhibitors for S. aureus but also a valuable addition to enzyme
      toolbox of biocatalysis. The discovery of this lipase can be potentially
      important and could provide a new target for pharmaceutical intervention against
      S. aureus infection.

PMID- 25385357
TI  - Maternal lifestyle factors in pregnancy and congenital heart defects in
      offspring: review of the current evidence.
AB  - The prognosis of children with congenital heart defects(CHDs) continues to
      improve with advancing surgical techniques; however, lack of information about
      modifiable risk factors for malformations in cardiovascular development impeded
      the prevention of CHDs. We investigated an association between maternal lifestyle
      factors and the risk of CHDs, because epidemiological studies have reported
      conflicting results regarding maternal lifestyle factors and the risk of CHDs
      recently. A review published on 2007 provided a summary of maternal exposures
      associated with an increased risk of CHDs. As part of noninherited risk factors,
      we conducted a brief overview of studies on the evidence linking common maternal
      lifestyle factors, specifically smoking, alcohol, illicit drugs, caffeine, body
      mass index and psychological factors to the development of CHDs in offspring.
      Women who smoke and have an excessive body mass index(BMI) during pregnancy are
      suspected to be associated with CHDs in offspring. Our findings could cause
      public health policy makers to pay more attention to women at risk and could be
      used in the development of population-based prevention strategies to reduce the
      incidence and burden of CHDs. However, more prospective studies are needed to
      investigate the association between maternal lifestyle factors and CHDs. 

PMID- 25385358
TI  - Microbispora sp. LGMB259 endophytic actinomycete isolated from Vochysia divergens
      (Pantanal, Brazil) producing beta-carbolines and indoles with biological
      activity.
AB  - Endophytic actinomycetes encompass bacterial groups that are well known for the
      production of a diverse range of secondary metabolites. Vochysia divergens is a
      medicinal plant, common in the "Pantanal" region (Brazil) and was focus of many
      investigations, but never regarding its community of endophytic symbionts. During
      a screening program, an endophytic strain isolated from the V. divergens, was
      investigated for its potential to show biological activity. The strain was
      characterized as Microbispora sp. LGMB259 by spore morphology and molecular
      analyze using nucleotide sequence of the 16S rRNA gene. Strain LGMB259 was
      cultivated in R5A medium producing metabolites with significant antibacterial
      activity. The strain produced 4 chemically related beta-carbolines, and 3
      Indoles. Compound 1-vinyl-beta-carboline-3-carboxylic acid displayed potent
      activity against the Gram-positive bacterial strains Micrococcus luteus NRRL B
      2618 and Kocuria rosea B-1106, and was highly active against two human cancer
      cell lines, namely the prostate cancer cell line PC3 and the non-small-cell lung
      carcinoma cell line A549, with IC50 values of 9.45 and 24.67 uM, respectively. 1
      Vinyl-beta-carboline-3-carboxylic acid also showed moderate activity against the
      yeast Saccharomyces cerevisiae ATCC204508, as well as the phytopathogenic fungi
      Phyllosticta citricarpa LGMB06 and Colletotrichum gloeosporioides FDC83.

PMID- 25385359
TI  - Intramolecular annulation of aromatic rings with N-sulfonyl 1,2,3-triazoles:
      divergent synthesis of 3-methylene-2,3-dihydrobenzofurans and 3-methylene-2,3
      dihydroindoles.
AB  - The controllable synthesis of 3-methylene-2,3-dihydrobenzofurans 2 and 3
      methylene-2,3-dihydroindoles 5 has been developed through Rh-catalyzed
      intramolecular annulation of aromatic rings with azavinyl carbenes. 

PMID- 25385360
TI  - Oral conjugated linoleic acid supplementation enhanced glycogen resynthesis in
      exercised human skeletal muscle.
AB  - Present study examined the effects of conjugated linoleic acid (CLA)
      supplementation on glycogen resynthesis in exercised human skeletal muscle.
      Twelve male participants completed a cross-over trial with CLA (3.8 g/day for 8
      week) or placebo supplements by separation of 8 weeks. CLA is a mixture of trans
      10 cis-12 and cis-9 trans-11 isomers (50:50). On experiment day, all participants
      performed 60-min cycling exercise at 75% VO2 max, then consumed a carbohydrate
      meal immediately after exercise and recovered for 3 h. Biopsied muscle samples
      from vastus lateralis were obtained immediately (0 h) and 3 h following exercise.
      Simultaneously, blood and gaseous samples were collected for every 30 min during
      3-h recovery. Results showed significantly increased muscle glycogen content with
      CLA after a single bout of exercise (P < 0.05). Muscle glucose transporter type 4
      expression was significantly elevated immediately after exercise, and this
      elevation was continued until 3 h after exercise in CLA trial. However, P-Akt/Akt
      ratio was not significantly altered, while glucose tolerance was impaired with
      CLA. Gaseous exchange data showed no beneficial effect of CLA on fat oxidation,
      instead lower non-esterified fatty acid and glycerol levels were found at 0 h.
      Our findings conclude that CLA supplementation can enhance the glycogen
      resynthesis rate in exercised human skeletal muscle.

PMID- 25385361
TI  - Editorial: the BAFFling immunology of systemic lupus erythematosus: beyond B
      cells.

PMID- 25385362
TI  - Single-dose, open-label study of the differences in pharmacokinetics of
      colchicine in subjects with renal impairment, including end-stage renal disease.
AB  - BACKGROUND AND OBJECTIVE: The effect of renal impairment on colchicine
      pharmacokinetics in patients with chronic kidney disease (CKD) has not been
      studied previously. We evaluated the effect of renal impairment on colchicine
      pharmacokinetics in patients with CKD. METHODS: The pharmacokinetics and safety
      of a single, oral 0.6-mg dose of colchicine was evaluated in an open-label study
      in eight healthy subjects with normal renal function; eight subjects each with
      mild, moderate, or severe renal impairment; and eight subjects with end-stage
      renal disease (ESRD) who received a single dose prior to receiving, and again
      following, hemodialysis. RESULTS: Colchicine exposure was similar for subjects
      with normal renal function, mild impairment, or ESRD prior to and during
      hemodialysis (24.7-31.7 ng.h/mL), but was up to twofold higher in subjects with
      moderate or severe renal impairment (48.9 and 48.0 ng.h/mL, respectively). A very
      small amount of the colchicine dose (mean of 5.2 %) was recovered in dialysate.
      CONCLUSIONS: It appears that patients with mild or moderate renal impairment or
      those actively receiving hemodialysis do not show accumulation of colchicine,
      whereas those with severe renal impairment show a doubling of exposure. All
      patients with renal impairment taking colchicine should be closely monitored,
      especially as many patients taking colchicine often have other comorbidities and
      may be taking other medications.

PMID- 25385363
TI  - Effects of phenobarbital and levetiracetam on PR and QTc intervals in patients
      with post-stroke seizure.
AB  - BACKGROUND AND OBJECTIVES: Sudden unexplained/unexpected death (SUDEP) is related
      to high mortality in patients with epilepsy. The prolongation of QT interval,
      involved in cardiac arrhythmia-related SUDEP, may be precipitated by
      antiepileptic drugs (AEDs). In this study, we evaluated the effects of
      phenobarbital and levetiracetam on PR-QTc intervals in patients with post-stroke
      seizures. METHODS: We performed an open-label, parallel group, prospective,
      multicenter study between June 2009 and December 2013 in patients older than 18
      years of age with a clinical diagnosis of post-stroke seizure and treated with
      phenobarbital or levetiracetam. In order to exclude a role of cerebral post
      stroke injury on modulation of PR and QTc intervals, patients with cerebral post
      stroke injury and without seizures were also enrolled as controls. RESULTS:
      Interictal electrocardiography analysis revealed no significant difference in PR
      interval between patients treated with an AED (n = 49) and control patients (n =
      50) (181.25 +/- 12.05 vs. 182.4 +/- 10.3 ms; p > 0.05). In contrast, a
      significantly longer QTc interval was recorded in patients treated with an AED
      compared with control patients (441.2 +/- 56.6 vs. 396.8 +/- 49.3 ms; p < 0.01).
      Patients treated with phenobarbital showed a significantly longer QTc interval
      than patients treated with levetiracetam (460.0 +/- 57.2 vs. 421.5 +/- 50.1 ms; p
      < 0.05). CONCLUSIONS: The study reported that in patients with late post-stroke
      seizures, phenobarbital prolonged QTc interval more so than levetiracetam.

PMID- 25385364
TI  - Evaluation of essential oils in beef cattle manure slurries and applications of
      select compounds to beef feedlot surfaces to control zoonotic pathogens.
AB  - AIMS: To evaluate natural terpene compounds for antimicrobial activities and
      determine whether these compounds could be used to control microbial activities
      and pathogens in production animal facilities. METHODS AND RESULTS: Thymol,
      geraniol, glydox, linalool, pine oil, plinol and terpineol were tested in
      laboratory studies for ability to control the production of odorous volatile
      fatty acid compounds and reduce pathogen levels in manure slurry preparations.
      Thymol is a terpene phenolic compound and was most effective for reducing
      fermentation products and pathogen levels (P < 0.05), followed by the extracts
      linalool, pine oil and terpineol, which are terpene alcohols. Select compounds
      thymol, linalool and pine oil were further evaluated in two separate studies by
      applying the agents to feedlot surfaces in cattle pens. Feedlot surface material
      (FSM; manure and soil) was collected and analysed for fermentation products,
      levels of coliforms and total Escherichia coli, and the presence of E. coli
      O157:H7, Campylobacter, Salmonella, Listeria and L. monocytogenes. The reduction
      in fermentation products but not pathogens was dependent on the moisture present
      in the FSM. Treatment with 2000 ppm thymol reduced the prevalence of E. coli
      O157:H7 but not Listeria. In a separate study, treatment with 4000 ppm pine oil
      reduced E. coli O157:H7, Listeria and Campylobacter (P < 0.05). Linalool was
      tested at two levels (2000 and 4000 ppm) and did not affect pathogen levels at
      either concentration. CONCLUSIONS: Natural compounds bearing terpenes can control
      pathogenic bacteria in treated manures and when applied to the feedlot surface in
      production cattle systems. Pine oil is a cheaper alternative to thymol and may be
      a useful treatment for controlling pathogens. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The control of bacterial pathogens in animal productions systems is an
      important step in preharvest food safety. Waste products, such as pine oil
      extract, from the pulp wood industry may have application for treating feedlot
      pens and manures to reduce the pathogen load.

PMID- 25385365
TI  - MicroRNA-30a-5p in the prefrontal cortex controls the transition from moderate to
      excessive alcohol consumption.

PMID- 25385366
TI  - Modeling non-syndromic autism and the impact of TRPC6 disruption in human
      neurons.
AB  - An increasing number of genetic variants have been implicated in autism spectrum
      disorders (ASDs), and the functional study of such variants will be critical for
      the elucidation of autism pathophysiology. Here, we report a de novo balanced
      translocation disruption of TRPC6, a cation channel, in a non-syndromic autistic
      individual. Using multiple models, such as dental pulp cells, induced pluripotent
      stem cell (iPSC)-derived neuronal cells and mouse models, we demonstrate that
      TRPC6 reduction or haploinsufficiency leads to altered neuronal development,
      morphology and function. The observed neuronal phenotypes could then be rescued
      by TRPC6 complementation and by treatment with insulin-like growth factor-1 or
      hyperforin, a TRPC6-specific agonist, suggesting that ASD individuals with
      alterations in this pathway may benefit from these drugs. We also demonstrate
      that methyl CpG binding protein-2 (MeCP2) levels affect TRPC6 expression.
      Mutations in MeCP2 cause Rett syndrome, revealing common pathways among ASDs.
      Genetic sequencing of TRPC6 in 1041 ASD individuals and 2872 controls revealed
      significantly more nonsynonymous mutations in the ASD population, and identified
      loss-of-function mutations with incomplete penetrance in two patients. Taken
      together, these findings suggest that TRPC6 is a novel predisposing gene for ASD
      that may act in a multiple-hit model. This is the first study to use iPSC-derived
      human neurons to model non-syndromic ASD and illustrate the potential of modeling
      genetically complex sporadic diseases using such cells. 

PMID- 25385367
TI  - Developmental endothelial locus-1 is a homeostatic factor in the central nervous
      system limiting neuroinflammation and demyelination.
AB  - Inflammation in the central nervous system (CNS) and disruption of its immune
      privilege are major contributors to the pathogenesis of multiple sclerosis (MS)
      and of its rodent counterpart, experimental autoimmune encephalomyelitis (EAE).
      We have previously identified developmental endothelial locus-1 (Del-1) as an
      endogenous anti-inflammatory factor, which inhibits integrin-dependent leukocyte
      adhesion. Here we show that Del-1 contributes to the immune privilege status of
      the CNS. Intriguingly, Del-1 expression decreased in chronic-active MS lesions
      and in the inflamed CNS in the course of EAE. Del-1-deficiency was associated
      with increased EAE severity, accompanied by increased demyelination and axonal
      loss. As compared with control mice, Del-1(-/-) mice displayed enhanced
      disruption of the blood-brain barrier and increased infiltration of neutrophil
      granulocytes in the spinal cord in the course of EAE, accompanied by elevated
      levels of inflammatory cytokines, including interleukin-17 (IL-17). The augmented
      levels of IL-17 in Del-1-deficiency derived predominantly from infiltrated CD8(+)
      T cells. Increased EAE severity and neutrophil infiltration because of Del-1
      deficiency was reversed in mice lacking both Del-1 and IL-17 receptor, indicating
      a crucial role for the IL-17/neutrophil inflammatory axis in EAE pathogenesis in
      Del-1(-/-) mice. Strikingly, systemic administration of Del-1-Fc ameliorated
      clinical relapse in relapsing-remitting EAE. Therefore, Del-1 is an endogenous
      homeostatic factor in the CNS protecting from neuroinflammation and
      demyelination. Our findings provide mechanistic underpinnings for the previous
      implication of Del-1 as a candidate MS susceptibility gene and suggest that Del-1
      centered therapeutic approaches may be beneficial in neuroinflammatory and
      demyelinating disorders. 

PMID- 25385368
TI  - Schizophrenia genetics: emerging themes for a complex disorder.
AB  - After two decades of frustration, genetic studies of schizophrenia have entered
      an era of spectacular success. Advances in genotyping technologies and high
      throughput sequencing, increasing analytic rigour and collaborative efforts on a
      global scale have generated a profusion of new findings. The broad conclusions
      from these studies are threefold: (1) schizophrenia is a highly polygenic
      disorder with a complex array of contributing risk loci across the allelic
      frequency spectrum; (2) many psychiatric illnesses share risk genes and alleles,
      specifically, schizophrenia has substantial overlaps with bipolar disorder,
      intellectual disability, major depressive disorder and autism spectrum disorders;
      and (3) some convergent biological themes are emerging from studies of
      schizophrenia and related disorders. In this commentary, we focus on the very
      recent findings that have emerged in the past 12 months, and in particular, the
      areas of convergence that are beginning to emerge from multiple study designs. 

PMID- 25385370
TI  - Annexin A2 knockdown inhibits hepatoma cell growth and sensitizes hepatoma cells
      to 5-fluorouracil by regulating beta-catenin and cyclin D1 expression.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancer types, and
      chemotherapy plays an important role in treatment of HCC. However, long-term
      treatment with chemotherapeutic drugs such as 5-fluorouracil (5-FU) often results
      in chemoresistance, and the underlying mechanisms remain unclear. In this study,
      we showed that the annexin A2 (ANXA2) protein is highly expressed in hepatoma
      cells compared to healthy cells. Knockdown of the ANXA2 gene inhibited hepatoma
      cell growth, and the underlying mechanism may involve cell cycle inhibition
      through downregulation of beta-catenin and cyclin D1. We also investigated the
      role of ANXA2 in chemotherapeutic treatment with 5-FU. 5-FU inhibited hepatoma
      cell growth, while ANXA2 overexpression reduced, and knockdown enhanced, the
      effects of 5-FU on hepatoma cell growth. Furthermore, beta-catenin and cyclin D1
      were asscociated with the ANXA2-induced resistance. Taken together, our data
      suggest that the ANXA2 protein is a critical factor in HCC and that its
      downregulation can enhance chemotherapeutic treatment with 5-FU. ANXA2 may thus
      constitute a new therapeutic target for HCC.

PMID- 25385371
TI  - [Pay attention to patient's visual function in oculoplastic surgery for
      congenital blepharophimosis syndrome].
AB  - Blepharophimosis is characterized by the presence of a narrowed horizontal
      palpebral aperture, ptosis, epicanthus inversus, and telecanthus. Due to
      patient's eye deformity, both of his or her appearance and psychological
      development are affected. In some cases, blepharophimosis not only influence the
      appearance but also the visual development. Therefore, patients with
      blepharophimosis require to be evaluated the visual function before the surgery
      in order to prevent amblyopia. In this article, we conclude that we should pay
      close attention to patient's visual function before and after the surgery. The
      timing of surgery must weigh the balance between early surgery to prevent
      amblyopia and late surgery for more reliable ptosis measurement, which provides a
      better surgical outcome.

PMID- 25385372
TI  - [How to choose appropriate surgical approach in removal of the eyeball].
AB  - We often consult patients with non-functional eye caused by trauma, intraocular
      malignancy, absolute stage of glaucoma and other diseases who need to remove the
      eyeball in our clinical work. Eye removal is an irreversibly destructive
      procedure, which mainly include enucleation and evisceration. There are various
      surgical techniques which are still controversial. Both of the two procedures
      have their own advantages, disadvantages, indications and contraindications. The
      ophthalmologists should comprehensively consider the disease situations, medical
      conditions and the requirements of the patients when choosing appropriate
      surgical approach to remove the eyeball.

PMID- 25385373
TI  - [Whether external dacryocystorhinostomy will be abandoned].
AB  - External dacryocystorhinostomy (DCR) has long been considered as the gold
      standard treatment for nasolacrimal duct obstruction or chronic dacryocystitis.
      Recently, however, endoscopic endonasal DCR is becoming increasingly popular with
      the development of endoscopic surgery technique in naso-orbit related diseases.
      Endoscopic DCR has the advantages of avoiding an external incision scar and
      simultaneously handling with nasal conditions. Nevertheless, the new method also
      has some disadvantages, for example, the lower long-term success rate, the high
      technical requirement, long learning curves, expensive equipment and the high
      cost of surgery. The choice of the surgical approaches should be based on the
      patient's condition, experience of the surgeon and available resources. After
      nearly a century of proven, external DCR still has incomparable superiority and
      should receive widespread attention and application. 

PMID- 25385369
TI  - FASTKD2 is associated with memory and hippocampal structure in older adults.
AB  - Memory impairment is the cardinal early feature of Alzheimer's disease, a highly
      prevalent disorder whose causes remain only partially understood. To identify
      novel genetic predictors, we used an integrative genomics approach to perform the
      largest study to date of human memory (n=14 781). Using a genome-wide screen, we
      discovered a novel association of a polymorphism in the pro-apoptotic gene
      FASTKD2 (fas-activated serine/threonine kinase domains 2; rs7594645-G) with
      better memory performance and replicated this finding in independent samples.
      Consistent with a neuroprotective effect, rs7594645-G carriers exhibited
      increased hippocampal volume and gray matter density and decreased cerebrospinal
      fluid levels of apoptotic mediators. The MTOR (mechanistic target of rapamycin)
      gene and pathways related to endocytosis, cholinergic neurotransmission,
      epidermal growth factor receptor signaling and immune regulation, among others,
      also displayed association with memory. These findings nominate FASTKD2 as a
      target for modulating neurodegeneration and suggest potential mechanisms for
      therapies to combat memory loss in normal cognitive aging and dementia. 

PMID- 25385374
TI  - [Clinical characterization of severe orbital complications after endoscopic sinus
      surgery].
AB  - OBJECTIVE: To summarize the clinical feature of severe orbital complications
      after endoscopic sinus surgery and to explore the precautions. METHODS: A
      retrospective review study. Twenty-two cases of severe orbital complications
      after endoscopic sinus surgery between January 2002 and December 2012 were
      included. The main parameters for analyzing were history of paranasal sinuses,
      clinical manifestation of complications, imaging findings, site of injury, the
      relationship between injury site and clinical signs. RESULTS: Twenty-two cases of
      patients with serious complications, including: visual loss in 7 cases (32%),
      ptosis in 5 cases (23%), ocular position deviation in 15 cases (68%), limitation
      of ocular motility in 17 cases (77%), enophthalmos in 10 cases (45%). Imaging
      display: medial rectus involvement in 14 cases, inferior rectus involvement in 6
      cases. The most common site of entry into the orbit was the medial orbital wall
      (14 cases, 64%), followed by the inferomedial wall (6 cases, 27%). Radiological
      imagings showed the medial displacement of optic nerve in 7 cases (32%) and
      foreign bodies in the orbit or paranasal sinuses in 8 cases (36%). Medical
      treatment was given in 1 cases and surgical repair in 9 cases. Removal of foreign
      bodies was performed in 6 cases. One patient received inferior rectus and orbital
      wall repair, but no improvement in ocular movement. Orbital reconstruction for
      endophthalmos was performed in two cases. The improvement was recorded only in
      one case. CONCLUSIONS: The most severe complication is vision loss and the most
      common complication is limitation of ocular motility and ocular position
      deviation. The most common site of injury was within the rectus muscle, often
      accompanied by the defect of inner wall. Except foreign bodies, other
      complications were difficult to treat with poor prognosis. Emphasis should be
      placed on prevention.

PMID- 25385375
TI  - [Efficacy of endoscopic transcaruncular approach to reconstruct isolated medial
      orbital fracture].
AB  - OBJECTIVE: To study the efficacy of endoscopic transcaruncular approach in the
      repair of isolated medial orbital fracture. METHODS: It was a retrospective case
      series study.Retrospective chart was reviewed in 21 patients (21 eyes) receiving
      endoscopic transcaruncular approach to reconstruct isolated medial orbital
      fracture at Quzhou People's Hospital from May 2011 to May 2012. RESULTS: of
      visual acuity, diplopia, protrusion degree of both eyes and the movement of eye
      balls was recorded for analysis. RESULTS: All patients were followed up for 8-20
      months. There was no extrusion, rejection, infection or other complications of
      Medpor surgical implant during follow-up. There was no instance of decreased
      visual acuity at post-operation. The post-operative protrusion degree of both
      eyes was almost identical at less than 2 mm. The movement of eye balls was
      satisfactory in all directions. Diplopia disappeared in 13 cases, 1 case
      improved. CONCLUSION: Endoscopic transcaruncular approach is a safe and effective
      treatment in the repair of isolated medial orbital fracture.

PMID- 25385376
TI  - [Repair of full-thickness lower eyelid defect following surgical excision of
      malignant tumor using Hughes technique].
AB  - OBJECTIVE: To evaluate surgical outcome of reconstruction of full-thickness lower
      eyelid defect resulting from tumor excision. METHODS: A retrospective case series
      review of patients with lower eyelid malignant tumor who underwent surgical
      repair of full-thickness eyelid defect from June 2008 to May 2013 was made. The
      defect ranged from 50% to 80% of the lower eyelid after excision of tumor with
      frozen section control of the surgical margins. Hughes technique was used to
      reconstruct the posterior lamellar and local flap and free graft were fashioned
      to repair the anterior defect. The pedicle was divided at 1-3 months
      postoperatively. RESULTS: Of the 157 lower eyelid malignant tumors, the 3 most
      common types were basal cell carcinoma (107/157, 68.2%), sebaceous gland
      carcinoma (32/157, 20.4%), and malignant melanoma (10/157, 6.4%). Twenty-one
      eyelids of 21 patients (aged from 43 to 77 years old) were identified. No tumor
      recurred during follow-up period (8-60 months). There was only one case with
      squamous carcinoma metastasized to the parotid gland and then excised. The
      contour of all lower eyelids was satisfactory. No eyelid margin deformity or
      upper lid retraction was observed. Revision surgery was performed to treat lower
      lid entropion (3 patients), while mild lower lid retraction (2 patients) and
      temporary ectropion (one patient) required no management. CONCLUSION: Hughes
      flap, which is a posterior lamellar replacement for lower eyelid defect after
      removal of malignant tumor, achieves favorable functional and cosmetic results.

PMID- 25385377
TI  - [Morphological changes of corneal subbasal nerve plexus in patients with ocular
      blunt trauma by in vivo confocal microscope].
AB  - OBJECTIVE: To evaluate morphological changes of corneal subbasal nerve plexus in
      patients with ocular blunt trauma using in vivo confocal microscope. METHODS: A
      prospective study. Twenty-three consecutive zone 2 or zone 3 monocular contusion
      outpatients from the same ophthalmologist in the Affiliated Eye Hospital of
      Wenzhou Medical College were included in this study from December 2009 to
      December 2010. The 23 injured eyes divided into trauma group, and the
      contralateral 23 normal eyes were divided into control group. In vivo confocal
      microscope (IVCM) was performed in both groups at the first week after injury,
      and in trauma group at the first and the third month after injury. The main
      parameters for analyzing were corneal subbasal nerve plexus density, nerve
      trunks, nerve branching, total nerve number, and nerve tortuosity. Data were
      analyzed using a paired t-test and Wilcoxon signed-rank test to compare the
      difference of parameters between the control group and each time point of trauma
      group. A repeated measures analysis of variance (ANOVA) was used to analyze data
      on the three time points in the trauma group. RESULTS: All parameters of trauma
      group were changed significantly over time (F values: 16.272, 24.138, 63.393,
      68.122, 91.463, all P values < 0.01) . Corneal subbasal nerve plexus density,
      nerve trunks, nerve branching, total nerve number were significantly decreased at
      the first week [(624.0 +/- 109.9) um/frame, 1.66 line/frame, 6.70 line/frame,
      8.45 line/frame)] compared with control group [(1677.9 +/- 87.1) um/frame, 4.80
      line/frame, 8.98 line/frame, 13.80 line/frame) (t = 8.998, 9.301, 9.119, 12.969;
      all P < 0.01)], and showed a continued downward trend with time. However, nerve
      trunk showed no significant changes at the first week (1.66 line/frame) and the
      first month (2.31 line/frame) (t = -1.518; P = 0.143). Nerve tortuosity was
      significantly increased at the first week (1.66) compared with control group
      (1.00) (t = -6.879; P < 0.01) , and then kept increasing gradually. At the first
      month after injury, the nerve tortuosity (3.20) was more obvious than the first
      week (P < 0.01) , and nerve regeneration could be observed. At the third month,
      the values of each parameters were gradually approaching levels of control group.
      Nerve trunks (4.00 line/frame), nerve branching (8.69 line/frame), total nerve
      number (13.26 line/frame) and nerve tortuosity (1.00) of trauma group showed no
      significant difference compared with control group (t = 3.117, 1.703, 3.325, 
      1.837; P = 0.079,0.792,0.392,0.392) , but nerve density [(1064.3 +/-
      93.3)um/frame] was still less than control group (t = 5.736; P < 0.01). Injury of
      different zone showed no significant influence on all the parameters in trauma
      group (F values:0.119,0.032,0.296,0.053,0.143;P values:
      0.733,0.859,0.592,0.821,0.709). CONCLUSIONS: IVCM can clearly display the
      histological features of corneal subbasal nerve plexus in patients with ocular
      blunt trauma. Corneal subbasal nerve plexus were morphologically abnormal within
      3 months after injury, and gradually underwent from atrophy to regeneration over
      time.

PMID- 25385378
TI  - [Diagnostic accuracy of the immersion high-frequency B-scan ultrasonography in
      chemical injured eyes].
AB  - OBJECTIVE: To investigate the diagnostic accuracy of the immersion high-frequency
      B-scan ultrasonography, a noninvasive preoperative diagnosis method, in observing
      the anterior segment in chemical injured eyes. METHODS: It was a retrospective
      study. Sixty-three ocular chemical injury patients (63 eyes), who accepted the
      keratoplasty or the artificial cornea transplant in PLA General Hospital from May
      2011 to May 2013, were included in this study. All the injured eyes were examined
      by ultrasound bio-microscopy (UBM) and immersion high-frequency B-scan
      ultrasonography, respectively. The images were analyzed and the results were
      compared with the intraoperative findings. The observation of lens was the main
      parameter. RESULTS: All the 63 patients were examined with the UBM and the
      immersion high-frequency B-scan ultrasonography before the surgery. The findings
      of the cornea, anterior chamber angle, iris from UBM were consistent with those
      from the immersion high-frequency B-scan ultrasonography. As for the lens
      observation, in 32 eyes in which the lens were not detected by UBM, the lens were
      not detected in only 16 eyes, while 3 eyes with normal lens and 13 eyes with lens
      pacifications (1 eye with pyknotic lens) by immersion high-frequency B-scan
      ultrasonography. In 17 eyes in which the lens were found normal by UBM, there
      were only 14 eyes with normal lens and the rest 3 eyes' lens were found
      intumescent by immersion high-frequency B-scan ultrasonography. In 6 eyes in
      which lens were detected with suspicious by UBM, 2 eyes' lens were pyknotic and 4
      eyes' lens were intumescent or clouded by immersion high-frequency B-scan
      ultrasonography. The findings of immersion high-frequency B-scan ultrasonography
      were highly consistent with the intraoperative findings. CONCLUSIONS: The lens
      could be observed accurately by immersion high-frequency B-scan ultrasonography
      in chemical injured eyes.

PMID- 25385379
TI  - [Ocular manifestations of immune reconstitution inflammatory syndrome].
AB  - OBJECTIVE: To investigate the ocular manifestations of immune reconstitution
      inflammatory syndrome. METHODS: Retrospective study. 372 patients were diagnosed
      as acquired immune deficiency syndrome from April 1997 to December 2012. The
      examination included best-corrected visual acuity, slit-lamp biomicroscopy,
      mydriatic fundus examination and colored fundus photography. Systemic examination
      including CD4(+)T- lymphocyte count and HIV viral load test before and after
      HAART treatment. RESULTS: Fifty three eyes (33 patients) were diagnosed as
      cytomegalovirus retinitis, among which 16 eyes (10 patients) were later presented
      with immune reconstitution inflammatory syndrome after highly active anti
      retroviral therapy. There are 9 males and 1 female, aged from 24 to 57 years old,
      with a mean of (39.0 +/- 10.6) years old. The duration of HAART was 2 weeks to 2
      years, with a mean of 5.3 months. All of the 16 eyes had decreased visual acuity,
      and 2 eyes had floaters. The best corrected visual acuity (BCVA) was light
      perception in 2 eyes, hand move to 0.05 in 5 eyes, 0.1 to 0.5 in 6 eyes, 0.6 to
      1.0 in 3 eyes. 8 eyes appeared active iridocyclitis and 5 eyes appeared inactive
      iridocyclitis, 5 eyes had lens opacity, 9 eyes had vitreitis, 1 eye had pale
      optic disc, 2 eyes had optic disc edema, 4 eyes were found retinal detachment.
      CONCLUSION: The improvement of the understanding of the ocular manifestations of
      IRIS is essential for diagnosis and treatment.

PMID- 25385380
TI  - [Effects of decreased OPTN expression on the survival of the rat retinal ganglion
      cell line RGC5].
AB  - OBJECTIVE: To investigate the effects of decreased OPTN expression on the
      morphological alteration of sub-cellular structure and the survival of the rat
      retinal ganglion cell line RGC5. METHODS: Experimental study. OPTN specific siRNA
      was designed, synthesized and transfected into the astrocyte cell by
      Lipofectemine 2000. The mRNA and the protein of OPTN were assessed by real time
      polymerase chain reaction (real time-PCR) and Western Blot. Eukaryotic expressing
      plasimid of OPTN specific siRNA (si-OPTN) was constructed with the most effective
      RNA interference sequence and transfected into RGC5 by Lipofectemine 2000. The
      RGC5 was divided into 4 groups: blank control group, pEGFP positive group, si
      OPTN group, and liposome negative group. Specific fluorescent labeling dyes were
      used to mark the corresponding cell organelle. The distribution of optineurin and
      the morphology alteration of sub-cellular structure induced by the abnormal
      expression of optineurin in RGC5 were observed with confocal fluorescence
      microscopy. The effect of si-OPTN on cell survival was monitored by morphologic
      observation and PI-Hoechst33342 fluorescence staining of cells. One-way ANOVA was
      used between groups. RESULTS: After a 24 h transfection, the expression of OPTN
      mRNA was significantly inhibited by transfection of si-OPTN-001, si-OPTN-002 and
      si-OPTN-003 which was (61.71 +/- 0.84)%, (48.13 +/- 0.92)% and (46.22 +/- 0.73)%
      respectively comparing with negative control. Forty-eight hours after
      transfection, the protein expression of OPTN decreased to (64.44 +/- 2.01)%,
      (57.78 +/- 1.97)% and (37.78 +/- 1.84)% comparing with negative control. When
      cells were transfected after 24 h and 48 h, the transfecting efficiency of
      plasmids to RGC5 was (17.43 +/- 0.94)% and (20.13 +/- 1.24)% respectively. The
      distribution of si-OPTN was similar to EGFP. The green fluorescence distributed
      evenly in the cytoplasm and the nucleus. Compared with negative control, the
      morphology of filaments, mitochondria, lysosomes, and Golgi body had no
      significant alteration in si-OPTN group. By using fluorescent double staining of
      Hoechst33342 and PI and comparing with blank control group (0.74 +/- 0.34)% and
      negative control group (0.96 +/- 0.41)%, increased cell apoptosis was observed in
      positive control group and si-OPTN group obviously after a 24 h transfection (F =
      5.457, P < 0.05), but the apoptosis rate decreased in si-OPTN group comparing
      with that of positive control group (F = 6.541, P < 0.05). As the transfecting
      time extended, the apoptosis rate of positive control group increased when
      tranfecteing cultures reached 48 h. The apoptosis rate in si-OPTN group increased
      slightly with no significance (F = 3.212, P > 0.05). CONCLUSIONS: Si-OPTN-003 is
      the most effective siRNA in inhibiting the OPTN expression. The expression of si
      OPTN distributed evenly in the whole cell with no obvious injuries in the
      transfected cell. The down regulation of optineurin induced by si-OPTN could be
      decreased RGC5 cell death.

PMID- 25385381
TI  - [Top ten research advances of ophthalmology in China (2009-2013)].
AB  - In order to showcase the major research advances in ophthalmology of the recent
      five years (2009-2013) in China, the 11th Committee of the Ophthalmic Division of
      Chinese Medical Association launched the selection of Top Ten Research Advances
      of Ophthalmology in China. Each ophthalmic subspecialty group voted its top ten
      research advances and chose two out of ten to join the selection. The Committee
      voted top ten out from all candidates and announced the final result with honor.
      The following research advances were selected as the Top Ten Research Advances of
      Ophthalmology in China: Innovative theory and its application of fungal
      keratitis; Increased gradient pressure between IOP and ICP is the main cause of
      glaucomatous optic neuropathy; Domestic developed anti-VEGF medicine Conbercept
      has been applied successfully in the treatment of choriodal neovascularization;
      IL-23/IL-17 pathway and their regulation in the pathogenesis of uveitis; The
      creation of myopic animal model and the biochemical mechanism of myopia;
      Specialists' consensus on diagnosing amblyopia in children; Generation of induced
      pluripotent stem cells from human fibroblasts of the Tenon's capsule; The
      development and application of endoscopic navigation system in orbital surgery;
      Studies of pathogenesis on congenital cataract candidate gene mutations; The
      regulation for the diagnosis and treatment of pediatric retinal diseases in China
      and its extension. 

PMID- 25385382
TI  - [Surgical treatment of congenital glaucoma].
AB  - Congenital glaucoma is a type of disease which may seriously affect children's
      visual function. Different from adult glaucoma, medical therapy has a limited
      role and surgery remains the primary therapy. There are several types of surgical
      treatments for different patient. With the development of technology, more
      innovation surgeries, such as Trabectome(TM) and 360-degree suture trabeculotomy,
      are used in the treatment of congenital glaucoma with good result. At the same
      time, endoscopic technique is used in classical surgeries to break through their
      original limitations. This paper reviews the surgical treatments, their
      indications and latest developments. 

PMID- 25385383
TI  - [The option of neuroprotective therapeutics for glaucoma].
AB  - Glaucoma is the second common cause of irreversible blindness worldwide
      associated with a progressive neurodegenerative disease of retinal ganglion cells
      (RGC). The major hypothetical mechanisms of the apoptosis of RGCs includes
      deprivation of neurotrophic factors, excitotoxicity mediated by the interaction
      of glutamate with NMDAR. This article reviewed current development of three kinds
      of neuroprotective drugs for glaucoma management such as small-molecule
      therapeutics, recombinant therapeutic proteins and small-molecule bioactive
      peptides. Particularly, small peptides, which show high target specificity, high
      potency and low toxicity compared with small molecules, possession of the
      advantages of low immunogenicity and high cost-effectiveness over recombinant
      therapeutics, may become most important choice for neuroprotection against
      glaucoma of next generation. 

PMID- 25385384
TI  - [Recent progress in research on oxidative stress in glaucoma].
AB  - Apoptosis of retinal ganglion cells and progressive loss of the axons is an
      important feature of glaucoma, its pathogenesis is not exact. Some experimental
      and clinical study found that oxidative stress plays an important role in the
      onset and progression of glaucoma. Oxidative stress markers were found in
      glaucoma patient's serum and ocular tissue and anti-oxidative stress therapy also
      had a role in controlling glaucoma. In this review, we will discuss the oxidative
      stress pathogenesis and the antioxidant therapy in glaucoma. 

PMID- 25385385
TI  - Pattern of memory compromise in chronic geriatric schizophrenia, frontotemporal
      dementia and normal geriatric controls.
AB  - OBJECTIVE: The purpose of this study was to explore whether memory deficits in
      schizophrenia are attributable to poor organisation/encoding during initial
      learning vs. memory decay. METHODS: Subjects included geriatric
      schizophrenia/schizoaffective disorders [SSD; n = 37; age = 59.92 (55-74);
      education = 11.70 (7-18)]; frontotemporal dementia [FTD; n = 41; age = 76.59 (64
      83); education = 14.61 (12-20)] and geriatric controls [n = 107; age = 70.97 (55
      93); education = 13.76 (6-20)]. Subjects were administered the Wechsler Memory
      Scale, Third Edition and discrepancy scores between immediate and delayed
      subtests/indices were used to explore possible differences between groups in
      pattern of impairment. RESULTS: Significant differences were found between groups
      on age/education and these variables were related to several outcome measures.
      Gender was not related to diagnostic group and there were no gender differences
      on study variables. There were differences between the SSD subjects on several
      variables, with the schizoaffective subjects performing worse despite equivalence
      on global cognitive function, living status and chronicity. Seven one-way between
      subjects ANCOVAs compared groups on discrepancy scores. RESULTS failed to suggest
      differences between groups on immediate-delayed memory discrepancy scores (p >
      0.05). Subsequent analyses revealed differences in percentage retention scores
      between SSD and FTD on the faces subtest (p = 0.040), with SSD retaining greater
      information over time. CONCLUSION: RESULTS failed to show distinctions between
      groups on pattern of memory impairment when using discrepancy comparisons.
      However, an analysis examining percentage retention scores revealed better
      maintenance of non-contextual visual information over time in SSD. Findings may
      suggest deficits in immediate encoding rather than memory decay for some types of
      memory ability among geriatric SSD. Our failure to document group differences
      when using discrepancy comparisons may be attributable to relative similarity in
      pattern between groups or the limited sensitivity of this technique.

PMID- 25385386
TI  - Awareness of putative risk factors for Alzheimer's disease among elderly Koreans.
AB  - OBJECTIVE: Although there are rapidly growing concerns about the high rates of
      cognitive dysfunction in Korea, the knowledge of risk factors for Alzheimer's
      disease (AD) among the general public in Korea remains to be elucidated. METHODS:
      A total of 2767 randomly selected subjects from the Ansan Geriatric Study were
      questioned on their knowledge of putative risk factors for AD. Their answers were
      compared with their sociodemographic data and other variables. RESULTS: The most
      common stated risk factor was being older (59.6%), followed by head trauma
      (33.6%) and cerebrovascular disease (30.4%). However, a substandard education,
      which is a known risk factor, was considered significant by only 9.5% of the
      subjects. Predictors for a worse knowledge of the risk factors for AD were being
      older, a lower level of education, lower economic status and the attitude that
      dementia is not curable. CONCLUSION: This study revealed that misunderstanding
      about AD is more prevalent in older subjects and those with a lower level of
      education, and so public health education on the basic concepts of AD should be
      targeted at this population.

PMID- 25385387
TI  - Simulation study of stimulation parameters in desynchronisation based on the
      Hodgkin-Huxley small-world neural networks and its possible implications for
      vagus nerve stimulation.
AB  - Adopting small-world neural networks of the Hodgkin-Huxley (HH) model, the
      stimulation parameters in desynchronisation and its possible implications for
      vagus nerve stimulation (VNS) are numerically investigated. With the
      synchronisation status of networks to represent epilepsy, then, adding pulse to
      stimulations to 10% of neurons to simulate the VNS, we obtain the
      desynchronisation status of networks (representing antiepileptic effects). The
      simulations show that synchronisation evolves into desynchronisation in the HH
      neural networks when a part (10%) of neurons are stimulated with a pulse current
      signal. The network desynchronisation appears to be sensitive to the stimulation
      parameters. For the case of the same stimulation intensity, weakly coupled
      networks reach desynchronisation more easily than strongly coupled networks. The
      network desynchronisation reduced by short-stimulation interval is more distinct
      than that of induced by long stimulation interval. We find that there exist the
      optimal stimulation interval and optimal stimulation intensity when the other
      stimulation parameters remain certain. 

PMID- 25385388
TI  - Body dysmorphic disorder in patients with borderline personality disorder:
      prevalence, clinical characteristics, and role of childhood trauma.
AB  - OBJECTIVE: The prevalence of body dysmorphic disorder (BDD) in patients with
      borderline personality disorder (BPD) is unidentified. We hypothesised that BDD
      would be more common than realised in patients with BPD and comorbidity with BDD
      would result in a more severe clinical profile. Also, childhood trauma may play a
      predictive role in this association. METHODS: The study included 70 BPD in
      patients and 70 matched healthy controls. The subjects were evaluated with a
      comprehensive assessment battery using Structured Clinical Interview for DSM-IV
      Axis I Disorders (SCID-I), Structured Clinical Interview for DSM-III-R
      Personality Disorders (SCID-II) diagnostic tool for BDD, Global Assessment of
      Functioning, Traumatic Experiences Checklist and Hamilton Depression Rating
      Scale. RESULTS: The prevalence of BDD was 54.3% in the borderline sample. The BPD
      patients with BDD had significantly lower overall functioning and higher levels
      of BPD pathology, childhood traumatic experiences, suicide attempts, substance
      abuse and self-mutilation than those without BDD. Traumatic experiences were
      significant predictor of comorbid BDD diagnosis in BPD patients. CONCLUSIONS: Our
      results suggest a relatively high prevalence of BDD among patients with BPD, and
      co-occurrence of BDD and BPD remains to be clarified. The additional diagnosis of
      BDD in patients with BPD may cause a more severe global illness, and these two
      disorders may share, at least partly, a common psychopathologic mechanism.

PMID- 25385389
TI  - Interpreting neuropsychological impairment among adolescent inhalant users: two
      case reports.
AB  - OBJECTIVE: To illustrate the need to carefully consider mental health,
      psychosocial and motivational factors when investigating cognitive and
      intellectual impairment among chronic inhalant users. METHODS: Two adolescent
      chronic inhalant users with similar psychosocial disadvantages (eg unstable and
      dysfunctional families, state-based care, school absenteeism and forensic issues)
      and histories of comorbid drug use and mental health problems were assessed using
      a battery of paper and pencil and computerised neuropsychological tests. RESULTS:
      Contrary to the expectations of her case manager, one participant performed
      within the normal range for her age in all domains of intellectual ability, while
      the other participant, in line with the expectations of her case manger, showed
      marked cognitive deficits and intellectual disability. CONCLUSIONS: The typically
      complex presentation of chronic inhalant users (ie disadvantaged psychosocial
      backgrounds, comorbid psychopathology and poor motivation/engagement) is rarely
      considered when investigating associated cognitive and intellectual functioning.
      Future research should more carefully consider the role of such factors, given
      the evidence suggesting that they can considerably alter (accentuate or diminish)
      the association between inhalant abuse and neuropsychological impairment.

PMID- 25385391
TI  - Assessment of a Test for the Screening and Diagnosis of Celiac Disease.
AB  - BACKGROUND: Celiac disease (CD) is an immune-mediated intolerance to dietary
      gluten, affecting genetically predisposed individuals. ELISA-based serological
      tests help to decide if further duodenal biopsy is necessary, for this the
      diagnostic kits have to be accurate, specific, and sensible. In this study, we
      investigate the performance of an ELISA that uses the purified cross-linked
      complex of tissue transglutaminase and gliadin, referred as the "neoepitope"
      (AESKULISA(r) tTG New Generation), as antigen. METHODS: We evaluated 41 newly
      diagnosed celiac patients, 18 celiac patients on gluten-free diet, and 169
      controls, comprising healthy subjects, patients affected by other autoimmune
      diseases, and patients affected by several non-autoimmune diseases. RESULTS AND
      CONCLUSION: The assay has an excellent performance. Due to its high level of
      diagnostic accuracy, this assay constitutes a new approach for the screening of
      celiac patients not only for the diagnosis of CD, but also for monitoring
      patients on gluten-free diet and their compliance. Moreover, cases of neoepitope
      positive subjects who were tested negative with "classical" serological markers
      could have a predictive value for this pathology. This aspect will require
      further studies of elaboration.

PMID- 25385390
TI  - Prospective relationships between sleep problems and substance use, internalizing
      and externalizing problems.
AB  - While research has shown that sleep problems and substance use are reciprocally
      associated in adults, much less is known about this association in early
      adolescence. The main aim of the current longitudinal study was to explore
      bidirectional relationships between sleep problems, substance use, internalizing
      and externalizing problems in young adolescents. A prospective design was used
      incorporating two waves (approximately 1 year interval). A total of 555 young
      adolescents (290 females, M age = 13.96) participated in this study. All
      participants completed self-report measures in classrooms during regular school
      hours (questionnaires about sleep quality and sleep hygiene were used to measure
      sleep problems). The results indicated that sleep problems predicted changes in
      substance use, internalizing and externalizing problems over time, but problem
      behaviours did not predict changes in sleep problems, adjusted for gender, age
      and puberty. One exception was that alcohol use negatively predicted changes in
      sleep problems. This study suggests that sleep problems are important precursors
      of substance use, internalizing and externalizing problems in adolescence.

PMID- 25385392
TI  - Transforming growth factor-beta1 small interfering RNA inhibits growth of human
      embryonic lung fibroblast HFL-I cells in vitro and defends against radiation
      induced lung injury in vivo.
AB  - In the present study, a human transforming growth factor-beta1 (TGF-beta1) small
      interfering RNA (siRNA) plasmid vector (TGF-beta1-siRNA) was constructed to
      investigate its effects on the proliferation and differentiation of human lung
      fibroblasts in vitro and its interference effects on radiation-induced lung
      injury in vivo. Reverse transcription quantitative polymerase chain reaction and
      enzyme linked immunosorbent assay revealed that the mRNA and protein expression
      of TGF-beta1 in the HFL-I cells were inhibited by TGF-beta1-siRNA and flow
      cytometry demonstrated a significant increase in apoptosis of the HFL-I cells.
      Adult, female, specific-pathogen-free C57BL/6 mice were used in the in vivo
      animal investigations and were randomly divided into the four following groups:
      control without any treatment, radiation alone, radiation followed by empty
      vector transfection and radiation followed by TGF-beta1-siRNA vector
      transfection. Hematoxylin and eosin and Van-Gieson staining revealed that certain
      radiation-induced histopathological changes of the lung, including inflammation,
      edema, the density of surface pulmonary interstitial collagen fibers in the
      alveolar septum, TGF-beta1-positive reactions in alveolar epithelial cells and
      pulmonary interstitial macrophages were less marked in the mice transfected with
      TGF-beta1-siRNA compared with the mice without transfection or those transfected
      with empty vectors. The serum levels of TGF-beta1 levels in the irradiated mice
      increased significantly at four weeks and peaked at eight weeks after radiation,
      compared with the control. Serum levels of TGF-beta1 in the irradiated mice
      transfected with TGF-beta1-siRNA also increased gradually and a significant
      difference was observed compared with those irradiated without transfection. The
      mRNA expression levels of TGF-beta1 in the mice transfected with TGF-beta1-siRNA
      were markedly lower compared with those of the other radiation groups. The
      present study suggested that the TGF-beta1-siRNA vector reduced the activity of
      TGF-beta1 by downregulating the mRNA expression of TGF-beta1 and thereby
      effectively suppressing inflammatory reactions and defending against radiation
      induced lung injury.

PMID- 25385393
TI  - Aneuploidy in spermatids of Robertsonian (Rb) chromosome heterozygous mice.
AB  - Rb translocations are chromosomal rearrangements frequently found in natural
      populations of the house mouse Mus musculus domesticus. The standard diploid
      karyotype of the house mouse consisting of 40 telocentric chromosomes may be
      reduced by the emergence of metacentric Rb chromosomes. Multiple simple Rb
      heterozygotes form trivalents exhibiting higher anaphase nondisjunction frequency
      and consequently higher number of unbalanced gametes than in normal males. This
      work will attempt to establish whether frequencies of aneuploidy observed in
      heterozygote spermatids of the house mouse M. musculus domesticus show
      differences in chromosomes derived from different trivalents. Towards this goal,
      the number and distribution frequency of aneuploidy was assessed via FISH
      staining of specific chromosomes of spermatids derived from 2n = 32 individuals.
      Our results showed that for a given set of target chromosomes, 90% of the gametes
      were balanced, resulting from alternate segregation, and that there were no
      differences (approx. 10%) in aneuploidy frequencies in chromosomes derived from
      different trivalents. These observations suggest that segregation effectiveness
      does not depend on the type of chromosomes involved in trivalents. As a
      consequence of the trivalent's configuration, joint segregation of the
      telocentric chromosomes occurs thus favoring their appearance together in early
      spermatids. Our data suggest that Rb chromosomes and their telocentric homologs
      are subject to architectural constraints placing them close to each other. This
      proximity may ultimately facilitate fusion between them, hence contributing to a
      prevalence of Rb metacentric chromosomes.

PMID- 25385394
TI  - First observations of fertilized eggs and preleptocephalus larvae of Rhinomuraena
      quaesita in the Vienna Zoo.
AB  - For the first time worldwide, fertilized eggs of ribbon eels (Rhinomuraena
      quaesita) hatched into feeding preleptocephali and could be kept alive for a
      period of seven days in the Vienna Zoo. The study reports on husbandry,
      behavioral observations and dimensions of eggs and preleptocephalus larvae.
      Furthermore, body color variations of ribbon eels in captivity do not reflect its
      sex or sexual maturity.

PMID- 25385395
TI  - Total synthesis and structural revision of (+)-uprolide G acetate.
AB  - The first, asymmetric total synthesis of the proposed structure of (+)-uprolide G
      acetate (UGA) is reported, and the spectral properties of the synthetic compound
      clearly differed from those reported for natural UGA. On the basis of
      comprehensive analysis of the NMR data, two possible structures for the natural
      UGA were proposed and their total synthesis achieved, thus leading to the
      identification and confirmation of the correct structure and absolute
      configuration of the natural UGA. This synthesis was enabled by development of a
      novel synthetic strategy, which revolved around three key cyclization reactions:
      an Achmatowicz rearrangement, Sharpless asymmetric dihydroxylation/lactonization,
      and ring-closing metathesis. These synthetic studies pave the way for further
      studies on this class of structurally unusual cytotoxic cembranolides. 

PMID- 25385396
TI  - Hypsarrhythmia assessment exhibits poor interrater reliability: a threat to
      clinical trial validity.
AB  - OBJECTIVE: Hypsarrhythmia is the classic interictal electroencephalographic
      pattern associated with infantile spasms, and characterized by high voltage,
      disorganization, and multifocal independent epileptiform discharges. Given this
      seemingly simple definition, one might expect excellent interrater reliability
      (IRR) in the identification of this pattern. Alternatively, it may be argued that
      assessments of voltage and disorganization are fairly subjective, and thus quite
      challenging in borderline cases. We sought to test the IRR of hypsarrhythmia
      assessment in a systematic fashion. METHODS: Six blinded pediatric
      electroencephalographers from four centers reviewed 22 electroencephalography
      (EEG) samples from patients with infantile spasms. Each sample was 5 min in
      duration and included only wakefulness. Raters determined if each EEG was
      abnormal and if hypsarrhythmia was present/absent, and characterized relevant
      features: voltage, organization, epileptiform discharges, slowing, interictal
      attenuations, symmetry, and synchrony. In addition, raters indicated their level
      of confidence for each assessment. Multirater kappa statistics (kappa) were
      calculated for the assessment of hypsarrhythmia and each feature. RESULTS:
      Although IRR was favorable in determining whether a study was normal or abnormal
      (kappa=0.89), reliability was unfavorable for assessment of hypsarrhythmia
      (kappa=0.40), modified hypsarrhythmia (kappa=0.47), high voltage (kappa=0.37),
      disorganization (kappa=0.22), multifocal epileptiform discharges (kappa=0.68),
      interictal voltage attenuations (kappa=0.21), slowing (kappa=0.20), asymmetry
      (kappa=0.26), and asynchrony (kappa=0.08). Despite generally unsatisfactory
      interrater agreement, raters consistently reported high confidence in
      assessments. SIGNIFICANCE: This study contradicts the view that hypsarrhythmia
      assessment is straightforward. Even small variability in the identification of
      hypsarrhythmia has potentially deleterious consequences for clinical care, as its
      presence or absence impacts decisions to pursue high-risk and high-cost
      therapies. These inconsistencies may similarly confound studies in which
      abolition of hypsarrhythmia is an outcome measure. There is a great need for
      practical, reliable, and unbiased measures of hypsarrhythmia.

PMID- 25385397
TI  - 5000 years old and still going strong.

PMID- 25385398
TI  - The future of transfusion and Africa.

PMID- 25385399
TI  - Transfusion medicine illustrated: Cerebral oxygenation during transfusion for
      profound anemia.

PMID- 25385400
TI  - Transfusion medicine illustrated: Thermal imaging of a red blood cell unit during
      storage and at the time of issue.

PMID- 25385402
TI  - Innocent until proven guilty: do neonatal red blood cell transfusions really
      cause posttransfusion hyperbilirubinemia?

PMID- 25385403
TI  - In reply.

PMID- 25385404
TI  - Induction of platelet refractoriness after myeloablative unrelated allogeneic
      hematopoietic peripheral blood progenitor cell transplant from HLA-sensitized
      female donor.

PMID- 25385405
TI  - Need to clarify the cause of hemolysis in case report of newborn with clinically
      significant hemolytic disease and passive transfer of anti-D from maternal RhIG.

PMID- 25385406
TI  - Chromium-induced diffuse dermatitis with lymph node involvement resulting from
      Langerhans cell histiocytosis after metal-on-metal hip resurfacing.
AB  - Total hip arthroplasty (THA) is a highly effective surgical treatment for severe
      joint involvement. However, due to the release of metal ions in the blood, the
      patients who undergo hip replacement with metal-on-metal (MOM) bearings may
      develop signs of allergic skin disease. We report a case of a 60-year-old man who
      had received MOM hip resurfacing 5 years earlier for osteoarthritis. He presented
      with a 3-year history of diffuse dermatitis that did not respond to
      antihistamines and corticosteroids and also had elevated serum levels of chromium
      and cobalt. A patch test revealed chromium-sulfate hypersensitivity. A skin
      biopsy showed nonspecific perivascular lymphocytic infiltrate associated with
      histiocytes. A biopsy of an inguinal lymph node demonstrated large aggregates of
      Langerhans cells, suggesting type IV delayed-type hypersensitivity. The
      prosthesis was replaced using ceramic-on-ceramic bearings and the dermatitis
      resolved after 3 months. The lymph nodes decreased in volume and the serum
      chromium levels normalized within 24 months of revision surgery. The high levels
      of serum ions associated with the metal debris from MOM-THAs may induce
      sensitization and type IV hypersensitivity reactions. Replacing the prosthesis
      using alternative coupling surfaces is the only approach that has the capacity to
      resolve these symptoms. Physicians who are not familiar with this issue may
      misdiagnose systemic symptoms and provide inadequate treatment. 

PMID- 25385408
TI  - Effect of a regular exercise programme on pelvic girdle and low back pain in
      previously inactive pregnant women: A randomized controlled trial.
AB  - OBJECTIVE: To determine whether participation in a group fitness class for
      pregnant women can prevent and treat pelvic girdle pain and low back pain.
      DESIGN: An observer-blinded randomized controlled trial. PARTICIPANTS: A total of
      105 sedentary, nulliparous pregnant women, mean age 30.7 years (standard
      deviation (SD) 4.0), mean pre-pregnancy body mass index (BMI) 23.8 (SD 4.3), were
      assigned to either control or exercise groups at mean gestation week 17.7 (SD
      4.2). METHODS: The exercise intervention followed the guidelines of American
      College of Obstetricians and Gynecologists and included a 60 min general fitness
      class, with 40 min of endurance training and 20 min of strength training
      including stretching, performed at least twice per week for a minimum of 12
      weeks. Outcome measures were number of women reporting pelvic girdle pain and low
      back pain after the intervention (mean pregnancy week 36.6 (SD 0.9)) and
      postpartum (mean 7.7 (SD 1.7)). RESULTS: There were no statistically significant
      differences between the exercisers and controls in numbers reporting the 2
      conditions after the intervention (pelvic girdle pain: odds ratio (OR) = 1.34, CI
      = 0.56-3.20 or low back pain: OR = 1.10, CI = 0.47-2.60) or postpartum (pelvic
      girdle pain: OR = 0.38, CI = 0.13-1.10 or low back pain: OR = 1.45, CI = 0.54
      3.94). A comparison of the women who had attended at least 80% of the weekly
      exercise classes with the control participants did not change the results.
      CONCLUSION: Participation in regular group fitness classes during pregnancy did
      not alter the proportion of women reporting pelvic girdle pain or low back pain
      during pregnancy or after childbirth.

PMID- 25385407
TI  - Treatment of vascular risk factors in patients with a diagnosis of Alzheimer's
      disease: a systematic review.
AB  - BACKGROUND: Increasing evidence suggests vascular risk factors (VRF) play a role
      in the pathogenesis of Alzheimer's disease (AD). Epidemiological studies have
      found associations between VRF and risk of AD. Treating VRF in patients with AD
      offers a potential treatment option but ineffective treatments should be avoided
      in this group who are frequently on multiple medications and in whom compliance
      may be challenging. METHODS: Studies containing information on the treatment of
      VRF in patients with a diagnosis of AD were identified using a defined search
      strategy. Randomised controlled trials and observational studies were included.
      RESULTS: The pre-specified search strategy retrieved 11,992 abstract articles,
      and 25 papers including those identified on review of reference lists and reviews
      met the inclusion criteria. Of these, 11 were randomised controlled trials (RCTs)
      and 14 observational studies. Observational studies suggested that a VRF package
      and treatment of hypertension and statin therapy may be associated with improved
      outcome but these studies suffered from potential bias. The few RCTs performed
      were mostly small with short duration follow-up, and do not provide clear
      evidence either way. CONCLUSIONS: Observational data raises the possibility that
      treating VRF could alter the rate of decline in AD. However RCT data are not yet
      available to support this hypothesis and to alter clinical practice. RCTs in
      larger numbers of individuals with longer follow-up, ideally in the early stages
      of AD, are required to address this potentially important treatment question.

PMID- 25385409
TI  - Isolated hyperglycaemia does not increase VLDL-triacylglycerol secretion in type
      1 diabetic men.
AB  - AIMS/HYPOTHESIS: In type 1 diabetes, abnormalities of both glucose and
      lipoprotein metabolism are seen. The relationship between these factors is not
      understood, but studies indicate that hyperglycaemia may increase hepatic VLDL
      triacylglycerol (VLDL-TG) secretion and reduce VLDL-TG fatty acid oxidation,
      which could lead to the development of dyslipidaemia. The aim of this study was
      to determine the isolated effect of hyperglycaemia on VLDL-TG and NEFA kinetics
      in men with type 1 diabetes. METHODS: VLDL-TG and palmitate kinetics were
      measured in eight men with type 1 diabetes using ex vivo labelled VLDL-TG and
      palmitate tracers. A 2.5 h basal period (plasma glucose 5 mmol/l) was followed by
      a 4 h hyperglycaemic period (plasma glucose 16 mmol/l). Steady-state VLDL-TG
      kinetics (VLDL-TG secretion, clearance and oxidation rates) were assessed by an
      isotope dilution technique using an intravenous primed-constant infusion of ex
      vivo labelled [1-(14)C]VLDL-TG in combination with sampling of blood and expired
      air. Palmitate turnover was measured using [9,10-(3)H]palmitate. RESULTS: The
      VLDL-TG secretion rate (36.0 +/- 9.6 vs 30.8 +/- 6.1 MUmol/min, NS) and clearance
      rate (209 +/- 30.4 vs 197 +/- 41.7 ml/min, NS) were unchanged during the basal
      and hyperglycaemic periods, resulting in unchanged VLDL-TG concentrations (0.25
      +/- 0.11 MUmol/l vs 0.28 +/- 0.10 MUmol/l, NS). In addition, VLDL-TG fatty acid
      oxidation and palmitate flux were not changed during hyperglycaemia.
      CONCLUSIONS/INTERPRETATION: Four hours of acute hyperglycaemia (16 mmol/l)
      without a concomitant increase in insulin does not alter VLDL-TG and NEFA
      kinetics in men with type 1 diabetes. CLINICAL TRIAL REGISTRY NUMBER:
      NCT01178957.

PMID- 25385410
TI  - Inflammatory arthritis: Blood coagulation factor drives arthritis pathogenesis.

PMID- 25385411
TI  - Rheumatoid arthritis: Methotrexate and bridging glucocorticoids in early RA.

PMID- 25385413
TI  - Connective tissue diseases: Deficient antigen-specific T cell responses in SLE
      prone mice.

PMID- 25385412
TI  - Glucocorticoid-induced osteoporosis: who to treat with what agent?
AB  - Among the adverse events of glucocorticoid treatment are bone loss and fractures.
      Despite available, effective preventive measures, many patients receiving or
      initiating glucocorticoid therapy are not appropriately evaluated and treated for
      bone health and fracture risk. Populations with, or at risk of, glucocorticoid
      induced osteoporosis (GIOP) to target for these measures are defined on the basis
      of dose and duration of glucocorticoid therapy and bone mineral density. That
      patients with GIOP should be treated as early as possible is generally agreed
      upon; however, diversity remains in intervention thresholds and management
      guidelines. The FRAX((r)) algorithm provides a 10-year probability of fracture
      that can be adjusted according to glucocorticoid dose. There is no evidence that
      GIOP and postmenopausal osteoporosis respond differently to treatments. Available
      anti-osteoporotic therapies such as anti-resorptives including bisphosphonates
      and the bone anabolic agent teriparatide are effective for the management of
      GIOP. Prevention with calcium and vitamin D supplementation is less effective
      than specific anti-osteoporotic treatment. Anti-osteoporotic treatment should be
      stopped at the time of glucocorticoid cessation, unless the patient remains at
      increased risk of fracture. 

PMID- 25385415
TI  - Connective tissue diseases: New criteria improve recognition of early systemic
      sclerosis.

PMID- 25385414
TI  - The changing clinical picture and epidemiology of spondyloarthritis.
AB  - In the past decade, major progress has been made in the recognition,
      classification and treatment of spondyloarthritis (SpA). Classification criteria
      have been developed for axial and peripheral SpA by the Assessment of
      SpondyloArthritis international Society (ASAS) as a response to new insight into
      the clinical picture and unmet needs. The ASAS criteria have contributed to a
      better understanding of the full spectrum of axial and peripheral SpA and of the
      potential for treatment. However, whether all patients fulfilling these criteria
      should be considered as having true SpA is a matter of debate. Furthermore, the
      implementation of the ASAS criteria might lead to an increase in the reported
      prevalence of SpA, as patients who were previously unidentified could now be
      classified as having the disease, which might have consequences for healthcare
      budgets. In this Review, the changes in the clinical picture and epidemiology of
      SpA are discussed in light of the ASAS classification criteria for SpA. 

PMID- 25385416
TI  - Rheumatoid arthritis: Developing new oral targeted therapies for RA can be
      challenging.

PMID- 25385417
TI  - Laparoscopic sleeve gastrectomy prevents the deterioration of renal function in
      morbidly obese patients over 40 years.
AB  - BACKGROUND: Chronic kidney disease (CKD) risk has been associated with elevated
      body mass index (BMI), especially in morbidly obese subjects. Aging and obesity
      can play a synergic effect on accelerating the renal function deterioration.
      Bariatric surgery (mainly gastric bypass or biliopancreatic diversion) has
      demonstrated an improvement on renal function, but little is known about the
      potential effect of sleeve gastrectomy on renal function. METHODS: A prospective
      observational study was performed. Between 2009 and 2013, 50 morbidly obese
      patients over 40 years underwent a laparoscopic sleeve gastrectomy (LSG) at our
      institution. Renal function was evaluated by serum creatinine, urea, and
      estimated glomerular filtration rate (eGFR), calculated using the MDRD-4 formula.
      All the variables were obtained at three times: on the first visit to the
      surgeon's office (baseline), the day before surgery (preoperative), and 12 months
      after surgery. RESULTS: Fifty patients underwent a LSG, 44 females (88%) and 6
      males (12%), with a mean age 49.2 +/- 6.4 years and mean BMI of 48.4 +/- 7.7
      kg/m(2). MDRD-4 values presented a significant reduction (69.4 ml/min/m(2) at
      baseline vs 62.5 ml/min/m(2) preoperatively; CI95% (2.2-11.3 ml/min/m(2)); p =
      0.01). Comparing pre- and postoperative values, a significant reduction could be
      determined in creatinine (0.89 mg/dl preoperatively vs 0.71 mg/dl
      postoperatively; p = 0.01), urea (36.1 mg/dl preoperatively vs 29.8 mg/dl
      postoperatively; p = 0.023), and a significant increase in MDRD-4 (62.5
      ml/min/m(2) preoperatively vs 77.6 ml/min/m(2) postoperatively; p < 0.001).
      CONCLUSION: In patients over 40 years, renal function is going to deteriorate as
      long as the excess of weight persists. Laparoscopic sleeve gastrectomy has shown
      to improve the renal function 12 months after surgery.

PMID- 25385425
TI  - Prevalence of smoking among patients treated in NHS hospitals in England in
      2010/2011: a national audit.
AB  - Using data from The Health Improvement Network and Hospital Episode Statistics,
      we investigate smoking prevalence, number of smokers treated and opportunities
      for cessation intervention among patients treated in National Health Service
      (NHS) hospitals in England from April 2010 to March 2011. Our results show that
      approximately 1.1 million smokers are treated in English hospitals each year,
      receiving a total of 2.6 million episodes of care. These findings suggest that
      delivering smoking cessation as a routine component of hospital care, as
      recommended by recent National Institute for Health and Care Excellence guidance,
      could achieve marked reductions in the prevalence of smoking and improve the cost
      effectiveness of NHS hospitals. 

PMID- 25385424
TI  - Pharmacological inhibition and genetic knockdown of exchange protein directly
      activated by cAMP 1 reduce pancreatic cancer metastasis in vivo.
AB  - cAMP plays a critical role in regulating migration of various cancers. This role
      is context dependent and is determined by which of the two main cAMP sensors is
      at play: cAMP-dependent protein kinase or exchange protein directly activated by
      cAMP (EPAC). Recently, we have shown that the cAMP sensor protein EPAC1 promotes
      invasion/migration of pancreatic ductal adenocarcinoma (PDA) in vitro. In this
      study, we investigated the role of EPAC1 in invasion and metastasis of PDA in
      vivo, and evaluated the therapeutic potential of EPAC inhibitors as
      antimetastasis agents for this neoplasm. We employed an orthotopic metastatic
      mouse model in which the PDA cells MIA PaCa-2 were injected into the pancreas of
      athymic nude mice, and their local and distant spread was monitored by in vivo
      imaging and histologic evaluation of the number of metastatic foci in the liver.
      Either genetic suppression of EPAC1 or its pharmacologic inhibition with 3-(5
      tert-butyl-isoxazol-3-yl)-2-[(3-chloro-phenyl)-hydrazono]-3-oxo-propionitrile, an
      EPAC-specific antagonist recently identified in our laboratory, decreased
      invasion and metastasis of the PDA cells. Mechanistically, EPAC1 promotes
      activation and trafficking of integrin beta1, which plays an essential role in
      PDA migration and metastasis. Our data show that EPAC1 facilitates metastasis of
      PDA cells and EPAC1 might be a potential novel therapeutic target for developing
      antimetastasis agents for PDA. 

PMID- 25385426
TI  - Iron and oxygen sensing: a tale of 2 interacting elements?
AB  - Iron and oxygen metabolism are intimately linked with one another. A change in
      the level of either metabolite results in activation of common pathways. At the
      heart of these responses lies a group of iron and oxygen dependent enzymes called
      prolyl hydroxylases. Prolyl hydroxylases (PHDs) require both iron and oxygen for
      optimal activity and their biological activity is to carry out the critical post
      translational modification of the addition of a hydroxyl group to specific
      proline residues within Hypoxia Inducible Factor (HIFs)-well known transcription
      factors originally thought to regulate responses to hypoxia but which are now
      known to regulate key iron metabolism proteins too. The addition of the hydroxyl
      group ultimately leads to the unbiquitylation and destruction of HIFs, thus PHDs
      control appropriate HIF transcriptional responses depending on cellular oxygen or
      iron levels. There are two major HIFs; HIF1alpha and HIF2alpha. In terms of
      responses to iron HIF2alpha is of major importance in key tissues such as the
      intestine where several iron transporters (Ferroportin, Dcytb) contain HREs
      within their promoters which bind HIF2alpha. Furthermore the recent discovery
      that HIF2alpha contains a 5' iron responsive element (IRE) has underlined the
      importance of HIF2alpha as a major player in iron metabolism. This review brings
      together recent findings with regard to the HIF2alpha/IRP network as well as
      other aspects of iron sensing in cells and tissues. 

PMID- 25385427
TI  - Macitentan for the treatment of pulmonary arterial hypertension.
AB  - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious disease
      characterized by elevation of pulmonary artery pressures and right ventricular
      failure. It is a progressive disease with a poor 5-year survival despite recent
      advances in treatment. Endothelin plays an important role in the development and
      progression of the disease. Endothelin receptor blockers have been used to treat
      PAH since 2001. More recently, macitentan was approved for treatment of PAH. AREA
      COVERED: This review covers the preclinical and clinical data on macitentan.
      EXPERT OPINION: Macitentan is a more potent ERA and has been shown to delay
      progression of the disease. It does not appear to have any significant
      hepatotoxicity and has a convenient once-a-day dosing. In the large event driven
      trial, macitentan significantly reduced morbidity in patients with PAH. It was
      safe and well tolerated and the benefit was seen in treatment-naive patients and
      those already receiving PAH therapy.

PMID- 25385428
TI  - Developing an accurate method for estimating thyroid volume in calves using
      ultrasonography.
AB  - Diseases of the thyroid gland with struma formation can occur in calves suffering
      from iodine deficiency. The aim of the study was to develop a guideline for
      standardized ultrasonographic examination of the thyroid gland in order to
      determine its volume. Sonographic measurements of the thyroid lobes were carried
      out on three standardized axes in calves up to 3 months of age (n = 83). Total
      volume (V SON ) was calculated using the formula for an ellipsoid body. Forty
      three of the enrolled animals were euthanized. The lobes of their thyroid glands
      were dissected and measured with a slide gauge, and V SLG was calculated
      accordingly. In addition, thyroid volume was measured using the method of water
      displacement (V AQU ) and this was used as a gold standard in correlation and
      regression analyses with sonographic and slide gauge values. Intraobserver
      variability of sonographic measurements was dependent on side and axis, and
      ranged between 3.04% and 7.35%. In the euthanized calves with a body mass of 52.4
      +/- 17.1 kg, V SLG was 4.5 +/- 1.4 ml, V SON was 6.5 +/- 1.7 ml, and V AQU was
      7.9 +/- 2.4 ml (mean +/- standard deviation). Instead of the formula for
      ellipsoid bodies which underestimates thyroid volume, we developed a new formula
      derived from regression analysis. Body mass and thyroid volume correlated
      significantly. With the formula presented, thyroid volume of calves can be
      estimated by ultrasonographic measurement of three axes and compared to predicted
      values based on body mass.

PMID- 25385429
TI  - Chemical shift and fat suppression magnetic resonance imaging of thymus in
      myasthenia gravis.

PMID- 25385431
TI  - Unexpected 1,2-migration in metallasilabenzenes: theoretical evidence for
      reluctance of silicon to participate in pi bonding.
AB  - Density functional theory (DFT) calculations were carried out to investigate the
      1,2-migration in metallasilabenzenes. The results suggested that the chloride
      migration of metallabenzenes is unfavorable due to the loss of aromaticity in the
      nonaromatic analogues. In sharp contrast, such a migration in metallasilabenzenes
      is favorable due to the reluctance of silicon to participate in pi bonding. The
      migration of hydride and methyl group from the metal center to the silicon atom
      in metallasilabenzenes is computed to be also feasible. In addition, the pi donor
      ligand and the third row transition metal can stabilize metallasilabenzenes.
      Thus, such a migration becomes less favorable thermodynamically and kinetically.
      These findings could be very helpful for synthetic chemists to realize the first
      metallasilabenzene. 

PMID- 25385430
TI  - From cartoon to real time MRI: in vivo monitoring of phagocyte migration in mouse
      brain.
AB  - Recent studies have demonstrated that immune cells play an important role in the
      pathogenesis of many neurological conditions. Immune cells constantly survey the
      brain microvasculature for irregularities in levels of factors that signal
      homeostasis. Immune responses are initiated when necessary, resulting in
      mobilisation of the microglial cells resident in the central nervous system (CNS)
      and/or of infiltrating peripheral cells. However, little is known about the
      kinetics of immune cells in healthy and diseased CNS, because it is difficult to
      perform long-term visualisation of cell motility in live tissue with minimal
      invasion. Here, we describe highly sensitive in vivo MRI techniques for
      sequential monitoring of cell migration in the CNS at the single-cell level. We
      show that MRI combined with intravenous administration of super-paramagnetic
      particles of iron oxide (SPIO) can be used to monitor the transmigration of
      peripheral phagocytes into healthy or LPS-treated mouse brains. We also
      demonstrate dynamic cell migration in live animal brains with time-lapse MRI
      videos. Time-lapse MRI was used to visualise and track cells with low motility in
      a control mouse brain. High-sensitivity MRI cell tracking using SPIO offers new
      insights into immune cell kinetics in the brain and the mechanisms of CNS
      homeostasis. 

PMID- 25385432
TI  - Risk factors and clinical outcomes for spontaneous rupture of pyogenic liver
      abscess.
AB  - OBJECTIVE: To evaluate the risk factors and clinical outcomes in patients with
      spontaneous rupture of pyogenic liver abscess (PLA). METHODS: A total of 602
      patients diagnosed with PLA between January 2004 and July 2013 were
      retrospectively analyzed. Among them, 23 patients experienced a spontaneous
      rupture of liver abscess (SRLA). RESULTS: The prevalence of SRLA was 3.8%. Using
      multivariate analysis, liver cirrhosis (OR 4.651, P = 0.009), gas-forming
      abscesses (OR 3.649, P = 0.026), abscess >=6 cm in diameter (OR 10.989, P =
      0.002) and other septic metastases (OR 1.710, P = 0.047) were risk factors for
      SRLA. Regarding the site of rupture, 20 (87.0%) patients had a localized rupture,
      specifically, subphrenic abscess in 3 (13.0%), peri-hepatic abscess in 10
      (43.5%), localized peritoneal abscess in 3 (13.0%) and empyema in 4 (17.5%); and
      the other 3 (13%) had peritonitis. Ruptures resulting in peritonitis require
      urgent surgery, whereas localized ruptures were managed with surgical or
      percutaneous drainage in addition to appropriate antibiotics. The in-hospital
      mortality rate of SRLA was 4.3%. CONCLUSION: Patients with cirrhosis, having
      abscess >=6 cm in diameter, gas-forming abscesses and other septic metastases in
      those with PLA should be monitored closely and may need early intervention for
      SRLA.

PMID- 25385433
TI  - First prostate cancer audit calls for wider use of modern imaging techniques.

PMID- 25385434
TI  - The effect of the local use of chlorhexidine in surgical treatment of
      experimental peri-implantitis in dogs.
AB  - AIM: To evaluate the effect of surgical treatment of experimental peri
      implantitis at implants with different surface characteristics using different
      anti-infective procedures. MATERIAL AND METHODS: Four implants with different
      surface characteristics (A: TiOblast, B: OsseoSpeed, C: AT-I, D: TiUnite) were
      installed in a randomized order in each side of the mandible in 6 labrador dogs 3
      months after tooth extraction. Experimental peri-implantitis was induced 3 months
      later. Surgical treatment of peri-implantitis was performed. The implants were
      cleaned with gauze soaked in either saline (control) or chlorhexidine (test).
      Clinical and radiographical examinations were performed and microbiological
      samples were taken during a 6-month period after surgery. Biopsies were obtained
      and prepared for histological analysis. RESULTS: Clinical signs of soft tissue
      inflammation were reduced after surgical therapy in most test and control sites.
      While the analysis of bone level alterations in radiographs together with
      histological and microbiological assessments of resolution of peri-implantitis
      lesions failed to demonstrate statistically significant differences between test
      and control procedures, the evaluations disclosed significant differences between
      implant D and implants A, B and C on treatment outcome. CONCLUSION: It is
      suggested that (i) the local use of chlorhexidine has minor influence on
      treatment outcome, (ii) resolution of peri-implantitis following surgical
      treatment without the adjunctive use of local and systemic antimicrobial agents
      is possible and (iii) the results are influenced by implant surface
      characteristics.

PMID- 25385435
TI  - High dermatophyte contamination levels in hairdressing salons of a West African
      suburban community.
AB  - Tinea capitis is a dermatophyte infection of scalp is commonly spread by
      currently infected patients, asymptomatic carriers or by fomites, such as
      hairdressing tools. However, studies on the risk factors of Tinea capitis remain
      scarce. The aim of this study was to evaluate the dermatophytes contamination
      level of the hairdressing tools to which hairdressing salon customers are exposed
      in Sirakoro-Meguetana, a suburb of Bamako, the capital city of Mali. A total of
      41 hairdressing tools were sampled in five hairdressing salons. Two
      anthropophilic dermatophytes species, Microsporum audouinii (53.3%) and
      Trichophyton soudanense (46.7%), were cultured from 30 (73.2%) samples. This
      first study, addressing hairdressing salons dermatophyte contamination, revealed
      a strikingly high contamination of hairdressing tools with dermatophyte
      propagules, which exposes hairdressing salons customers to an important
      dermatophytosis risk. The sterilisation of hairdressing tools is central to
      preventing dermatophytoses spreading. Appropriate community information and
      hairdressers training should be implemented in this view. 

PMID- 25385437
TI  - Redox activity and pi bonding in a tripodal seven-coordinate molybdenum(VI)
      tris(amidophenolate).
AB  - A tris(aminophenol), tris(2-(3',5'-di-tert-butyl-2'-hydroxyphenyl)amino-4
      methylphenyl)amine, MeClampH6, is prepared in three steps from tri-p-tolylamine.
      The ligand reacts with dioxomolybdenum(VI) bis(acetylacetonate) to form an oxo
      free heptadentate complex, (MeClamp)Mo, with a capped octahedral geometry. The
      molybdenum is formally in the +6 oxidation state, with significant pi donation of
      the amidophenolates, as judged by intraligand bond distances. Two ligand-based
      oxidations and one metal-centered reduction are observed by cyclic voltammetry.
      Analysis of the optical spectrum of the compound gives an estimate of the
      energetic stabilization of the ligand pi orbitals by bonding to the molybdenum of
      approximately 0.9 eV, corresponding to about 40 kcal mol(-1) per pi bond.

PMID- 25385436
TI  - Functional compensation between Myc and PI3K signaling supports self-renewal of
      embryonic stem cells.
AB  - c-Myc and phosphatidylinositol 3-OH kinase (PI3K) both participate in diverse
      cellular processes, including cell cycle control and tumorigenic transformation.
      They also contribute to preserving embryonic stem cell (ESC) characteristics.
      However, in spite of the vast knowledge, the molecular relationship between c-Myc
      and PI3K in ESCs is not known. Herein, we demonstrate that c-Myc and PI3K
      function cooperatively but independently to support ESC self-renewal when murine
      ESCs are cultured under conventional culture condition. Interestingly, culture of
      ESCs in 2i-condition including a GSK3beta and MEK inhibitor renders both PI3K and
      Myc signaling dispensable for the maintenance of pluripotent properties. These
      results suggest that the requirement for an oncogenic proliferation-dependent
      mechanism sustained by Myc and PI3K is context dependent and that the 2i
      condition liberates ESCs from the dependence of this mechanism.

PMID- 25385438
TI  - Raised incidence of ankylosing spondylitis among Inuit populations could be due
      to high HLA-B27 association and starch consumption.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory arthritis mainly affecting
      the spinal joints. It would appear that the most likely causative agent in the
      development of AS is an environmental factor in the genetically susceptible, HLA
      B27 positive, individuals. Extensive data from several countries support the
      notion that Klebsiella pneumonia bacteria are the most likely culprit in the
      causation of AS. These microbes possess antigens which resemble HLA-B27 and
      spinal collagens. Increased intake of high-starch diet is directly proportional
      to the gut-associated bacterial load, especially in the large intestine, and
      among these microbial agents, Klebsiella is considered as one of the main
      constituting components. Therefore, a low-starch diet intake alongside the
      currently used medical therapeutic modalities could be beneficial in the
      management of patients with early AS. It is suggested that a change in the
      dietary habits from high protein, low-starch marine components to the Westernized
      high-starch diet among the Inuit peoples of Alaska and Canada could be considered
      as one of the main contributing factors in the increased prevalence of AS during
      the last few decades within this genetically unmixed native population. 

PMID- 25385440
TI  - Parental Anxiety Prospectively Predicts Fearful Children's Physiological Recovery
      from Stress.
AB  - Parental anxiety confers risk for the development of an anxiety disorder in
      children, and this risk may be transmitted through children's stress reactivity.
      Further, some children may be more vulnerable to reactivity in the presence of
      parent factors such as anxiety. In this study, we examined whether parents'
      anxiety symptoms prospectively predict school-aged children's physiological
      reactivity following stress, assessed through their electrodermal activity
      (galvanic skin response) during recovery from a performance challenge task, and
      whether this varies as a function of children's temperamental fearfulness.
      Parents and their children (N = 68) reported on their anxiety symptoms at Time 1
      of data collection, and parents characterized the extent to which their children
      had fearful temperaments. At Time 2 children completed the performance challenge
      and two recovery tasks. Greater parental anxiety symptom severity at Time 1
      predicted children's higher electrodermal response during both recovery tasks
      following the failure task. Further, these effects are specific to children with
      medium and high fearful temperament, whereas for children low in fearfulness, the
      association between parent anxiety and child reactivity is not significant.
      Findings provide additional evidence for the diathesis-stress hypothesis and are
      discussed in terms of their contribution to the literature on developmental
      psychopathology. 

PMID- 25385439
TI  - Insulin-like growth factor-I inhibition with pasireotide decreases cell
      proliferation and increases apoptosis in pre-malignant lesions of the breast: a
      phase 1 proof of principle trial.
AB  - INTRODUCTION: Estrogen inhibition is effective in preventing breast cancer in
      only up to 50% of women with precancerous lesions and many experience side
      effects that are poorly tolerated. As insulin-like growth factor I (IGF-I)
      underlies both estrogen and progesterone actions and has other direct effects on
      mammary development and carcinogenesis, we hypothesized that IGF-I inhibition
      might provide a novel approach for breast cancer chemoprevention. METHODS: In
      total, 13 women with core breast biopsies diagnostic of atypical hyperplasia (AH)
      were treated for 10 days with pasireotide, a somatostatin analog which uniquely
      inhibits IGF-I action in the mammary gland. They then had excision biopsies. 12
      patients also had proliferative lesions and one a ductal carcinoma in situ
      (DCIS). Primary outcomes were changes in cell proliferation and apoptosis after
      treatment. Expression of estrogen receptor (ER), progesterone receptor (PR), and
      phosphorylated Insulin-like growth factor I receptor (IGF-1R), protein kinase B
      (AKT) and extracellular signal-regulated kinases 1/2 (ERK1/2) were also assessed.
      Core and excision biopsies from 14 untreated patients served as non-blinded
      controls. Hyperglycemia and other side effects were carefully monitored. RESULTS:
      Pasireotide decreased proliferation and increased apoptosis in all AH (from 3.6
      +/- 2.6% to 1.3 +/- 1.2% and from 0.3 +/- 0.2% to 1.5 +/- 1.6%, respectively) and
      proliferative lesions (from 3.8 +/- 2.5% to 1.8 +/- 1.8% and from 0.3 +/- 0.2% to
      1.3 +/- 0.6%, respectively). The DCIS responded similarly. ER and PR were not
      affected by pasireotide, while IGF-1R, ERK1/2 and AKT phosphorylation decreased
      significantly. In contrast, tissue from untreated controls showed no change in
      cell proliferation or phosphorylation of IGF-1R, AKT or ERK 1/2. Mild to moderate
      hyperglycemia associated with reduced insulin levels was found. Glucose fell into
      the normal range after discontinuing treatment. Pasireotide was well tolerated
      and did not cause symptoms of estrogen deprivation. CONCLUSIONS: IGF-I inhibition
      by pasireotide, acting through the IGF-1R, was associated with decreased
      proliferation and increased apoptosis in pre-malignant breast lesions and one
      DCIS. Assuming hyperglycemia can be controlled, these data suggest that
      inhibiting the IGF-I pathway may prove an effective alternative for breast cancer
      chemoprevention. TRIAL REGISTRATION: NCT01372644 Trial date: July 1, 2007.

PMID- 25385441
TI  - Will incremental hemodialysis preserve residual function and improve patient
      survival?
AB  - The progressive loss of residual renal function in peritoneal dialysis patients
      is associated with increased mortality. It has been suggested that incremental
      dialysis may help preserve residual renal function and improve patient survival.
      Residual renal function depends upon both patient related and dialysis associated
      factors. Maintaining patients in an over-hydrated state may be associated with
      better preservation of residual renal function but any benefit comes with a
      significant risk of cardiovascular consequences. Notably, it is only
      observational studies that have reported an association between dialysis patient
      survival and residual renal function; causality has not been established for
      dialysis patient survival. The tenuous connections between residual renal
      function and outcomes and between incremental hemodialysis and residual renal
      function should temper our enthusiasm for interventions in this area. 

PMID- 25385442
TI  - MicroRNA-602 and microRNA-608 regulate sonic hedgehog expression via target sites
      in the coding region in human chondrocytes.
AB  - OBJECTIVE: Hedgehog (HH) signaling has recently been associated with cartilage
      degradation in osteoarthritis (OA). Because interleukin-1beta (IL-1beta) has been
      implicated as a principal instigator of OA, we sought to determine whether IL
      1beta induces the expression of sonic HH (SHH) and its regulation by microRNAs
      (miRNAs) in human chondrocytes. METHODS: Expression of SHH protein in human OA
      cartilage and in an animal model of OA was determined by immunohistochemical
      analysis and immunofluorescence analysis, respectively. Gene and protein
      expression in IL-1beta- or SHH-stimulated OA chondrocytes was determined by
      TaqMan assays and Western blotting, respectively. The effect of overexpression of
      miRNA-602 (miR-602) and miR-608 or their antagomirs on SHH expression was
      evaluated by transient transfection of human chondrocytes and HEK 293 cells. The
      role of signaling pathways was evaluated using small molecule inhibitors. Binding
      of miRNAs with the putative seed sequence in SHH messenger RNA (mRNA) was
      validated using a luciferase reporter assay. RESULTS: Expression of SHH, patched
      1, Gli-1, HH-interacting protein, matrix metalloproteinase 13 (MMP-13), and
      Colalpha1(X) was high in damaged OA cartilage. In damaged cartilage and in IL
      1beta-stimulated OA chondrocytes, expression of SHH was inversely correlated with
      expression of miR-608. Cotransfection of OA chondrocytes with miR-608 or miR-602
      mimic inhibited reporter activity, and mutation of the miRNA seed sequences
      abolished the repression of reporter activity. Overexpression of miR-602 or miR
      608 inhibited the expression of SHH mRNA and protein, and this was abrogated by
      antagomirs. Stimulation with recombinant human SHH protein up-regulated MMP-13
      expression, and inhibition of HH signaling blocked MMP-13 expression in OA
      chondrocytes. CONCLUSION: MiR-602 and miR-608 are important posttranscription
      regulators of SHH expression in OA chondrocytes, and their suppression by IL
      1beta may contribute to the enhanced expression of SHH and MMP-13 in OA.

PMID- 25385443
TI  - Impact of priming on the response of neutrophils to human neutrophil alloantigen
      3a antibodies.
AB  - BACKGROUND: Human neutrophil alloantigen-3a (HNA-3a) antibodies can induce
      transfusion-related acute lung injury (TRALI). The severity of TRALI varies
      largely among the affected patients. Severe comorbidity seems to increase the
      susceptibility for TRALI, potentially by priming of neutrophils. Thus, the impact
      of neutrophil priming on HNA-3a antibody-mediated neutrophil aggregation and
      CD11b surface expression was investigated. STUDY DESIGN AND METHODS: Neutrophils
      were primed using formyl-methionyl-leucyl-phenylalanine (fMLP) or bacterial
      lipopolysaccharide (LPS). Granulocyte aggregation and CD11b surface expression
      were evaluated by the granulocyte agglutination test and by flow cytometry (FC),
      respectively. Priming-induced changes in the surface expression of choline
      transporter-like protein 2 (CTL2) and the CTL2 mRNA expression were assessed by
      FC and quantitative real-time polymerase chain reaction, respectively. RESULTS:
      Priming of neutrophils lowered the amount of HNA-3a antibodies required for
      inducing granulocyte aggregation in a dose-dependent manner by 50% to 75%. The
      priming agent concentration necessary for this response differed between donors.
      Priming slightly enhanced binding of HNA-3a antibodies to neutrophils. However,
      CTL2 de novo synthesis was not induced after priming with LPS, indicating that
      increased HNA-3a antibody binding was likely caused by translocation of
      intracellular CTL2 to the surface or by increased affinity of HNA-3a antibodies
      to CTL2. HNA-3a antibodies influenced CD11b surface expression on neutrophils
      only marginally, which was also not potentiated by priming with fMLP or LPS.
      CONCLUSION: This study provides experimental evidence supporting the "threshold
      model" of TRALI. Priming of neutrophils with fMLP or LPS increases their
      aggregation response to HNA-3a antibodies by lowering the required antibody
      amount.

PMID- 25385444
TI  - Propofol alleviates acute lung injury following orthotopic autologous liver
      transplantation in rats via inhibition of the NADPH oxidase pathway.
AB  - Acute lung injury (ALI) induced by liver transplantation is detrimental to
      patient survival, and therapeutic strategies remain limited. Thus, the protective
      effects of propofol, a commonly used anesthetic with antioxidative and anti
      inflammatory properties, were investigated in the present study on ALI induced by
      orthotopic autologous liver transplantation (OALT). The protective mechanism of
      propofol was determined to be associated with the inhibition of NADPH oxidase, by
      comparing its effects with the positive controls apocynin (AP; an NADPH oxidase
      inhibitor) and N-acegysteine (NAC; a scavenger of reactive oxygen species). The
      results demonstrated that two proteins (p47phox and gp91phox) of the NADPH
      oxidase system presented increased expression in rats with ALI induced by OALT,
      thus leading to increased activation of the oxidative stress and inflammatory
      reactions. Preconditioning with NAC or AP eliminated this increase, suggesting
      that antioxidative treatment, particularly with inhibitors of NADPH oxidase, is a
      promising protective strategy against ALI induced by OALT. Propofol
      preconditioning at a high (100 mg/kg) or low (50 mg/kg) dose promoted similar
      protective effects, with the high-dose propofol producing a more marked effect
      than the low dose. The results suggested that propofol may protect against ALI
      induced by OALT, the mechanism of which may involve a reduced oxidative stress
      and inflammatory reaction mediated by NADPH oxidase inhibition.

PMID- 25385448
TI  - Inhibition of green algae growth by corrole-based photosensitizers.
AB  - AIMS: This study was performed to examine the potential of photodynamic
      inactivation for growth inhibition of green algae through generation of singlet
      oxygen. METHODS AND RESULTS: Two cationic and two anionic corroles were
      investigated according to their photoinhibitive effect on two strains of green
      algae using visible light for photoexcitation. The development of biomass over
      the experimental period of 18 days was followed using absorptive properties of
      the algae samples. The anionic photosensitizers showed no significant
      phototoxicity, whereas the cationic photosensitizers caused a drastic reduction
      of biomass on a short time scale and also displayed long-term inhibition of algae
      growth. CONCLUSIONS: In general, it was proven that photodynamic inactivation of
      green algae is possible. Concluding from the results of this study, cationic
      photosensitizers are favourable for this task, while anionic photosensitizers are
      not suited. SIGNIFICANCE AND IMPACT OF THE STUDY: Phototrophic biofilms are an
      important factor in biofouling and biodeterioration of building materials,
      causing great damage to historic and contemporary constructions. Growth
      inhibition of phototrophic organisms using photodynamic inactivation could pose
      an alternative to the use of biocides. To this end, successful application of
      this approach on green algae is a vital step in the development of suitable
      photosensitizers.

PMID- 25385446
TI  - Interethnic differences in pharmacokinetics of antibacterials.
AB  - BACKGROUND: Optimal antibacterial dosing is imperative for maximising clinical
      outcome. Many factors can contribute to changes in the pharmacokinetics of
      antibacterials to the extent where dose adjustment may be needed. In acute
      illness, substantial changes in important pharmacokinetic parameters such as
      volume of distribution and clearance can occur for certain antibacterials. The
      possibility of interethnic pharmacokinetic differences can further complicate
      attempts to design an appropriate dosing regimen. Factors of ethnicity, such as
      genetics, body size and fat distribution, contribute to differences in
      absorption, distribution, metabolism and elimination of drugs. Despite extensive
      previous work on the altered pharmacokinetics of antibacterials in some patient
      groups such as the critically ill, knowledge of interethnic pharmacokinetic
      differences for antibacterials is limited. OBJECTIVES: This systematic review
      aims to describe any pharmacokinetic differences in antibacterials between
      different ethnic groups, and discuss their probable mechanisms as well as any
      clinical implications. METHODS: We performed a structured literature review to
      identify and describe available data of the interethnic differences in the
      pharmacokinetics of antibacterials. RESULTS: We found 50 articles that met our
      inclusion criteria and only six of these compared antibacterial pharmacokinetics
      between different ethnicities within the same study. Overall, there was limited
      evidence available. We found that interethnic pharmacokinetic differences are
      negligible for carbapenems, most beta-lactams, aminoglycosides, glycopeptides,
      most fluoroquinolones, linezolid and daptomycin, whereas significant difference
      is likely for ciprofloxacin, macrolides, clindamycin, tinidazole and some
      cephalosporins. In general, subjects of Asian ethnicity achieve drug exposures up
      to two to threefold greater than Caucasian counterparts for these antibacterials.
      This difference is caused by a comparatively lower volume of distribution and/or
      drug clearance. CONCLUSION: Interethnic pharmacokinetic differences of
      antibacterials are likely; however, the clinical relevance of these differences
      is unknown and warrants further research.

PMID- 25385450
TI  - Association between psoriasis and asthma: a population-based retrospective cohort
      analysis.
AB  - BACKGROUND: Both psoriasis and asthma are chronic immune-mediated inflammatory
      diseases. OBJECTIVES: To evaluate the risk of developing asthma in patients with
      psoriasis compared with controls. METHODS: This cohort study was conducted using
      data from the Taiwan National Health Insurance Research Database. Patients with
      psoriasis (n = 10,288) and matched comparison patients without psoriasis (n =
      41,152) were evaluated. A Cox proportional hazard regression analysis was used to
      determine the risk of asthma in patients with and without psoriasis. RESULTS: The
      risk of asthma was 1.38-fold higher [95% confidence interval (CI) 1.23-1.54] in
      the cohort with psoriasis than in the reference cohort, after adjusting for age,
      sex and comorbidities. The incidence of asthma in men and women with psoriasis
      exhibited nonsignificant differences. Among all patients aged > 50 years,
      psoriasis was associated with a higher risk of asthma compared with not having
      psoriasis [adjusted hazard ratio (HR) 1.49; 95% CI 1.18-1.88 (in patients aged 50
      64 years); adjusted HR 1.63; 95% CI 1.34-1.99 (in patients aged > 65 years)].
      CONCLUSIONS: Our results indicate that patients with psoriasis are associated
      with a increased risk of developing asthma.

PMID- 25385449
TI  - Australian smokers' support for plain or standardised packs before and after
      implementation: findings from the ITC Four Country Survey.
AB  - BACKGROUND: Plain packaging (PP) for tobacco products was fully implemented in
      Australia on 1 December 2012 along with larger graphic health warnings. Using
      longitudinal data from the Australian arm of the ITC Four Country Survey, we
      examined attitudes to the new packs before and after implementation, predictors
      of attitudinal change, and the relationship between support and quitting
      activity. METHODS: A population-based cohort study design, with some cross
      sectional analyses. Surveys of Australian smokers assessed attitudes to PP at
      four time points prior to implementation (from 2007 to 2012) and one post
      implementation wave collected (early/mid-2013). RESULTS: Trend analysis showed a
      slight rise in opposition to PP among smokers in the waves leading up to their
      implementation, but no change in support. Support for PP increased significantly
      after implementation (28.2% pre vs 49% post), such that post-PP more smokers were
      supportive than opposed (49% vs 34.7%). Multivariate analysis showed support
      either before or after implementation was predicted by belief in greater adverse
      health impacts of smoking, desire to quit and lower addiction. Among those not
      supportive before implementation, having no clear opinion about PP (versus being
      opposed) prior to the changes also predicted support post-implementation. Support
      for PP was prospectively associated with higher levels of quitting activity.
      CONCLUSIONS: Since implementation of PP along with larger warnings, support among
      Australian smokers has increased. Support is related to lower addiction, stronger
      beliefs in the negative health impacts of smoking, and higher levels of quitting
      activity.

PMID- 25385447
TI  - The overlap between vascular disease and Alzheimer's disease--lessons from
      pathology.
AB  - Recent epidemiological and clinico-pathological data indicate considerable
      overlap between cerebrovascular disease (CVD) and Alzheimer's disease (AD) and
      suggest additive or synergistic effects of both pathologies on cognitive decline.
      The most frequent vascular pathologies in the aging brain and in AD are cerebral
      amyloid angiopathy and small vessel disease. Up to 84% of aged subjects show
      morphological substrates of CVD in addition to AD pathology. AD brains with minor
      CVD, similar to pure vascular dementia, show subcortical vascular lesions in
      about two-thirds, while in mixed type dementia (AD plus vascular dementia),
      multiple larger infarcts are more frequent. Small infarcts in patients with full
      blown AD have no impact on cognitive decline but are overwhelmed by the severity
      of Alzheimer pathology, while in early stages of AD, cerebrovascular lesions may
      influence and promote cognitive impairment, lowering the threshold for clinically
      overt dementia. Further studies are warranted to elucidate the many hitherto
      unanswered questions regarding the overlap between CVD and AD as well as the
      impact of both CVD and AD pathologies on the development and progression of
      dementia. 

PMID- 25385451
TI  - The relation of sexual dysfunction to depression and anxiety in patients with
      Parkinson's disease.
AB  - OBJECTIVE: In this study, we aimed to find out whether sexual dysfunction in
      patients with Parkinson's Disease (PD) was associated to PD-related disability
      and whether this relationship was modulated by depressive and anxiety symptoms.
      METHODS: Eighty-nine consecutive patients with idiopathic PD who attended to our
      movement disorders outpatient clinics between January 2011 and June 2014 were
      included in this study. The diagnosis of PD was confirmed by a movement disorders
      specialists in Neurology, according to UK Parkinson's Disease Society Brain Bank
      Criteria. The Unified PD Rating Scale (UPDRS) motor was used to assess motor
      disability and Hoehn and Yahr stage (H&Y) was used to establish disease severity.
      Cognitive function was assessed by the Mini-Mental State Examination. Patients
      were also administered the Hamilton depression (HAMD) and anxiety (HAMA) rating
      scales. The sexual functions of the patients were rated by applying the Turkish
      version of the Arizona Sexual Experiences Scale (ASEX). RESULTS: The mean age at
      the time of the study visit was 67.74+/-9.05. Male/female ratio was 1.87. Mean
      UPDRS total was 29.06+/-13.96 and mean UPDRS motor was 17.62+/-9.07. Mean HAMD
      score was 13.92+/-10.86, 58.4% of the patients had minor or major depression; and
      mean HAMA score was 7.94+/-6.49, 56.2% of the patients had minor or major
      anxiety. The mean ASEX score was 18.54+/-7.27 out of a maximum of 30. ASEX total
      scores were correlated with age, H&Y stage and HAMA scores. Age and also age at
      onset were correlated with ASEX subdomains except sexual desire. There was no
      correlation between disease duration and ASEX subdomains. UPDRS motor score was
      correlated with erection/lubrication. HAMD was only correlated with orgasm
      satisfaction. HAMA score was correlated with stimulation and orgasm. CONCLUSION:
      In patients with PD, there may be a common factor that modulates both depression,
      anxiety and sexual function. Further studies are needed to clarify the exact
      relationship.

PMID- 25385452
TI  - What boxing-related stimuli reveal about response behaviour.
AB  - When two athletes meet inside the ropes of the boxing ring to fight, their
      cognitive systems have to respond as quickly as possible to a manifold of stimuli
      to assure victory. In the present work, we studied the pre-attentive mechanisms,
      which form the basis of an athlete's ability in reacting to an opponent's
      punches. Expert boxers, beginner boxers and people with no experience of boxing
      performed a Simon-like task where they judged the colour of the boxing gloves
      worn by athletes in attack postures by pressing two lateralised keys. Although
      participants were not instructed to pay attention to the direction of the
      punches, beginner boxers' responses resembled a defence-related pattern, expert
      boxers' resembled counterattacks, whereas non-athletes' responses were not
      influenced by the unrelated task information. Results are discussed in the light
      of an expertise-related action simulation account. 

PMID- 25385454
TI  - Stones: Stones of any composition increase renal papillary density.

PMID- 25385455
TI  - Urinary incontinence: Comparing AFS and TVT for stress urinary incontinence.

PMID- 25385457
TI  - Infectious disease: Hidden chlamydia.

PMID- 25385458
TI  - Health policy: Male health--a recent paradigm.

PMID- 25385459
TI  - Prostate cancer: Better use of bone scans in prostate cancer.

PMID- 25385462
TI  - Gold(I)-catalyzed diazo cross-coupling: a selective and ligand-controlled
      denitrogenation/cyclization cascade.
AB  - An unprecedented gold-catalyzed ligand-controlled cross-coupling of diazo
      compounds by sequential selective denitrogenation and cyclization affords N
      substituted pyrazoles in a position-switchable mode. This novel transformation
      features selective decomposition of one diazo moiety and simultaneous
      preservation of the other one from two substrates. Notably, the choice of the
      ancillary ligand to the gold complex plays a pivotal role on the chemo- and
      regioselectivity of the reactions. 

PMID- 25385463
TI  - Clinical Impact of Regulatory T cells (Treg) in Cancer and HIV.
AB  - The role of regulatory T cells, (Treg) in human cancer and HIV-1 infections has
      been under intense scrutiny. While the lack of a marker specific for human Treg
      has made it challenging to phenotype these cells, combinations of several markers
      and functional attributes of Treg have made it possible to assess their
      contributions to immune homeostasis in health and disease. Treg diversity and
      their plasticity create a challenge in deciding whether they are beneficial to
      the host by down-regulating excessive immune activation or are responsible for
      adverse effects such as suppression of anti-tumor immune responses resulting in
      promotion of tumor growth. Treg are emerging as active participants in several
      biochemical pathways involved in immune regulation. This review attempts to
      integrate current information about human Treg in respect to their activities in
      cancer and HIV-1. The goal is to evaluate the potential of Treg as targets for
      future immune or pharmacologic therapies for cancer or HIV-1 infections. 

PMID- 25385465
TI  - Lead(II) binding to the chelating agent D-penicillamine in aqueous solution.
AB  - A spectroscopic investigation of the complexes formed between the Pb(II) ion and
      D-penicillamine (H2Pen), a chelating agent used in the treatment of lead
      poisoning, was carried out on two sets of alkaline aqueous solutions with CPb(II)
      ~ 10 and 100 mM, varying the H2Pen/Pb(II) molar ratio (2.0, 3.0, 4.0, 10.0).
      Ultraviolet-visible (UV-vis) spectra of the 10 mM Pb(II) solutions consistently
      showed an absorption peak at 298 nm for S(-) -> Pb(II) ligand-to-metal charge
      transfer. The downfield (13)C NMR chemical shift for the penicillamine COO(-)
      group confirmed Pb(II) coordination. The (207)Pb NMR chemical shifts were
      confined to a narrow range between 1806 ppm and 1873 ppm for all Pb(II)
      penicillamine solutions, indicating only small variations in the speciation, even
      in large penicillamine excess. Those chemical shifts are considerably deshielded,
      relative to the solid-state (207)Pb NMR isotropic chemical shift of 909 ppm
      obtained for crystalline penicillaminatolead(II) with Pb(S,N,O-Pen) coordination.
      The Pb LIII-edge extended X-ray absorption fine structure (EXAFS) spectra
      obtained for these solutions were well-modeled with two Pb-S and two Pb-(N/O)
      bonds with mean distances 2.64 +/- 0.04 A and 2.45 +/- 0.04 A, respectively. The
      combined spectroscopic results, reporting delta((207)Pb) ~ 1870 ppm and lambdamax
      ~ 298 nm for a Pb(II)S2NO site, are consistent with a dominating 1:2
      lead(II):penicillamine complex with [Pb(S,N,O-Pen)(S-HnPen)](2-n) (n = 0-1)
      coordination in alkaline solutions, and provide useful structural information on
      how penicillamine can function as an antidote against lead toxicity in vivo.

PMID- 25385466
TI  - A magnetic resonance spectroscopy study of antisocial behaviour disorder,
      psychopathy and violent crime among military conscripts.
AB  - BACKGROUND: Prefrontal and/or temporo-limbic abnormalities associated with
      antisocial personality disorder (APD), high psychopathy scores and violent
      behaviours can readily be evaluated by neuroimaging methods. OBJECTIVES: In this
      study, we compared the brain metabolites in adult male military conscripts with
      APD, high psychopathy scores and serious violent crimes (n = 15) with age- and
      educational-level-matched healthy controls (n = 15) by means of magnetic
      resonance spectroscopy. METHODS: All cases were diagnosed by means of the
      Diagnostic Statistical Manual-IV APD module of the Structured Clinical Interview
      for DSM III-R Axis II Disorders (SCID-II) semistructured questionnaire in
      Turkish. The psychopathy scores were evaluated by means of the Hare Psychopathy
      Checklist-Revised translated into Turkish (PCL-R). PCL-R is a 20-item, reliable
      and valid instrument for assessment of psychopathy, both in categorical and
      dimensional natures. All patients had a total score of 29 (of possible 40) or
      higher from PCL-R, indicating a high degree of psychopathy. RESULTS: Our results
      showed no significant differences in ratio of N-acetyl aspartate (NAA), creatine
      (Cr) and choline-related compounds in the right dorsolateral prefrontal cortex,
      anterior cingulate cortex (ACC) and amygdala-hippocampus regions of cases
      compared with controls. ACC NAA/Cr was significantly negatively correlated with
      both the PCL-R total score and the PCL-R factor I score (interpersonal/affective
      problems) among the cases. CONCLUSION: As ACC plays an important role in decision
      making and emotional information processing, we postulate that the lower NAA/Cr
      ratio, suggesting impaired neural integrity, may increase the severity of
      interpersonal/affective problems of the psychopathy factor in male subjects
      exhibiting APD, high psychopathy overall scores and violent crimes.

PMID- 25385467
TI  - Cognitive effects of acute tryptophan depletion in the healthy elderly.
AB  - BACKGROUND: Studies investigating the cognitive effects of serotonin depletion,
      using the technique of acute tryptophan depletion (ATD) by dietary means, have
      generally suggested that ATD impairs delayed verbal recall and recognition. In
      two previous studies in the elderly, this result has not been replicated and ATD
      impaired working memory. These results may be susceptible to type II error but a
      similar testing schedule in the individual studies allows data to be pooled in a
      larger analysis. METHODS: Data from two separate double-blind placebo-controlled
      studies of the effects of ATD on cognitive function in the elderly were combined.
      In one study, a low dose and in the other a high dose of amino acids was used. In
      a repeated measures analysis of variance, the effects of ATD and the interaction
      of this with the other factors (age, gender and dose) on cognitive measures was
      examined. RESULTS: Data from 31 healthy subjects aged between 60 and 81 years
      were analysed. There were no main effects of ATD or consistent interactions
      between ATD and age, gender or dose. There were significant interactions between
      ATD, gender and dose. When tryptophan depleted, females having the higher dose
      drink had reduced scores on Digit span and immediate recall on the Rey Auditory
      Verbal Learning Test. CONCLUSION: The enlarged data set did not confirm an
      overall effect of ATD on working memory or on delayed word recall but does
      suggest an effect of ATD on encoding or registration in the subgroup of females
      receiving a higher strength drink.

PMID- 25385468
TI  - Incidental brain MRI abnormalities in 60- to 64-year-old community-dwelling
      individuals: data from the Personality and Total Health Through Life study.
AB  - OBJECTIVE: There have been limited data available on the prevalence of structural
      brain abnormalities in asymptomatic individuals and a growing interest in the
      various ethical issues related to reporting of such findings. This study
      evaluated the prevalence of incidental abnormalities on brain magnetic resonance
      imaging (MRI) in a random sample of 60- to 64-year-old community-dwelling
      individuals as well as successfully followed a referral pathway taking into
      account of the various ethical issues related to the referral process. The
      Personality and Total Health (PATH) Project was designed to study the risk and
      protection factors of normal ageing, dementia and other neuropsychiatric
      disorders. METHOD: MRI scans were performed in randomly selected 478 healthy,
      community-dwelling 60- to 64-year-old individuals. All scans were reported for
      abnormalities by a radiologist. RESULTS: Abnormalities were detected in 22 (4.8%)
      subjects, comprising 10 tumours (pituitary adenoma 4, meningioma 3, suprasellar
      tumour 1, cavernous haemangioma 1, subarachnoid lipoma 1), 6 infarct-like
      lesions, 2 arachnoid cysts, 1 possible normal pressure hydrocephalus, and 1 each
      of unconfirmed aneurysm and mesial temporal sclerosis. Further evaluation led to
      novel intervention in one case of pituitary adenoma, and adjustment of drug
      treatment to modify risk factors in two cases with subclinical infarction.
      CONCLUSION: While no case required immediate referral or urgent surgical
      intervention, the change in the outcome of treatment of some cases suggests that
      appropriate referral process should be in place when researchers study large
      number of subjects in the community using MRI of the brain.

PMID- 25385469
TI  - Musical hallucinosis: case reports and possible neurobiological models.
AB  - OBJECTIVE: The perception of music without a stimulus, or musical hallucination,
      is reported in both organic and psychiatric disorders. It is most frequently
      described in the elderly with associated hearing loss and accompanied by some
      degree of insight. In this setting it is often referred to as 'musical
      hallucinosis'. The aim of the authors was to present examples of this syndrome
      and review the current understanding of its neurobiological basis. METHOD: We
      describe three cases of persons experiencing musical hallucinosis in the context
      of hearing deficits with varying degrees of associated central nervous system
      abnormalities. RESULTS: Putative neurobiological mechanisms, in particular those
      involving de-afferentation of a complex auditory recognition system by complete
      or partial deafness, are discussed in the light of current information from the
      literature. CONCLUSION: Musical hallucinosis can be experienced in those patients
      with hearing impairment and is phenomenologically distinct for hallucinations
      described in psychiatric disorders.

PMID- 25385472
TI  - Platelet Counts in Children With Henoch-Schonlein Purpura--Relationship to Renal
      Involvement.
AB  - BACKGROUND: The aim of this study is to identify the clinical and laboratory risk
      factors for renal involvement and to determine the relationship between platelet
      counts and renal involvement in (Henoch-Schonlein purpura) HSP patients. METHODS:
      We reviewed the medical records of 107 children with HSP according to Eular/Press
      diagnostic criteria. Clinical and laboratory parameters for renal involvement
      were evaluated and compared to no renal involvement. RESULTS: A retrospective
      study consisted of 107 children, 61 boys (57%), and 46 girls (43%). Twenty-eight
      of the 107 patients (26.1%) had renal involvement. The mean platelet count was
      significantly higher in patients with renal involvement when compared to patients
      without renal involvement (P = 0.001). The multivariate logistic regression
      analysis identified that age (P = 0.022), sex (P = 0.037), gastrointestinal
      involvement (P = 0.019), and platelet count (P = 0.019) were significantly
      associated with the renal involvement of HSP. The platelet count was predictive
      of renal involvement, which had odds ratio of 1.0, and achieved area under the
      curve of 0.66 for predicting the renal involvement within the acute stage of HSP
      (P = 0.009). CONCLUSION: Our study indicated that age, sex, gastrointestinal
      involvement, and platelet count were significant risk factors of renal
      involvement of HSP.

PMID- 25385470
TI  - Renal cell carcinoma.
AB  - The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15
      years. Progress in the surgical management of the primary tumor and increased
      understanding of the molecular biology and genomics of the disease have led to
      the development of new therapeutic agents. The management of the primary tumor
      has changed owing to the realization that clean margins around the primary lesion
      are sufficient to prevent local recurrence, as well as the development of more
      sophisticated tools and techniques that increase the safety of partial
      nephrectomy. The management of advanced disease has altered even more
      dramatically as a result of new agents that target the tumor vasculature or that
      attenuate the activation of intracellular oncogenic pathways. This review
      summarizes data from prospective randomized phase III studies on the surgical
      management and systemic treatment of RCC, and provides an up to date summary of
      the histology, genomics, staging, and prognosis of RCC. It describes the
      management of the primary tumor and offers an overview of systemic agents that
      form the mainstay of treatment for advanced disease. The review concludes with an
      introduction to the exciting new class of immunomodulatory agents that are
      currently in clinical trials and may form the basis of a new therapeutic approach
      for patients with advanced RCC. 

PMID- 25385471
TI  - Potential therapeutic mechanism of genistein in breast cancer involves inhibition
      of cell cycle regulation.
AB  - Genistein can prevent tumorigenesis and reduce the incidence of diseases that are
      dependent upon estrogen. Previous research, however, has shown that genistein can
      also increase the risk of breast cancer. Thus, the aim of the present study was
      to investigate the mechanism underlying the effect of genistein in breast cancer
      and to determine whether genistein produces a therapeutic effect or promotes the
      development of breast cancer. Gene microarray data obtained from three samples
      treated with alcohol (control group), three samples treated with 3 umol/l
      genistein and three samples treated with 10 umol/l genistein for 48 h, were
      downloaded from the Gene Expression Omnibus database. Analysis of the
      differentially expressed genes (DEGs) and functional enrichment in the two
      genistein groups was performed. The interaction networks of the DEGs were
      constructed and the overlapping network was extracted. Finally, the functions and
      pathways of the DEGs in the overlapping network were enriched. In total, 224 DEGs
      coexisted in the two genistein groups, and the most significant function of these
      was the cell cycle. The number and the fold change of expression values of the
      DEGs in the 10 umol/l genistein group were significantly higher compared with
      that of the 3 umol/l genistein group. The most significant function and pathway
      of the DEGs in the overlapping network was the cell cycle involving several
      genes, including GLIPR1, CDC20, BUB1, MCM2 and CCNB1. Thus, genistein stimulation
      resulted in gene expression changes in breast cancer cell lines and discrepancies
      increased with higher doses of genistein. The DEGs were most significantly
      associated with cell cycle regulation.

PMID- 25385473
TI  - Reliability and validity of a short version of the general functioning subscale
      of the McMaster Family Assessment Device.
AB  - The General Functioning 12-item subscale (GF12) of The McMaster Family Assessment
      Device (FAD) has been validated as a single index measure to assess family
      functioning. This study reports on the reliability and validity of using only the
      six positive items from the General Functioning subscale (GF6+). Existing data
      from two Western Australian studies, the Raine Study (RS) and the Western
      Australian Child Health Survey (WACHS), was used to analyze the psychometric
      properties of the GF6+ subscale. The results demonstrated that the GF6+ subscale
      had virtually equivalent psychometric properties and was able to identify almost
      all of the same families who had healthy or unhealthy levels of functioning as
      the full GF12 subscale. In consideration of the constraints faced by large-scale
      population-based surveys, the findings of this study support the use of a GF6+
      subscale from the FAD, as a quick and effective tool to assess the overall
      functioning of families. 

PMID- 25385474
TI  - Treatment of Ebola virus disease.

PMID- 25385475
TI  - Crystalloid fluid therapy: is the balance tipping towards balanced solutions?

PMID- 25385476
TI  - If antibiotics did not exist.

PMID- 25385477
TI  - Extracorporeal membrane oxygenation in severe accidental hypothermia.

PMID- 25385478
TI  - Transhepatic diaphragm echography for diaphragm paralysis in infants.

PMID- 25385479
TI  - VEGF-mediated suppression of cell proliferation and invasion by miR-410 in
      osteosarcoma.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate
      gene expression. The aberrant expression of miRNA has become a major focus in
      cancer research. This study aimed to investigate the importance of miR-410 in the
      diagnosis and therapy of osteosarcoma (OS). Western blot analysis showed that the
      expression of VEGF was higher in Saos-2 and MG-63 cells than that in three other
      OS cell lines. We also found that miR-410 was lowly expressed and inversely
      correlated with VEGF expression in OS specimens. Over-expression of miR-410 had a
      greater repression on VEGF expression than other candidate VEGF-targeting miRNAs.
      Luciferase reporter assay demonstrated that miR-410 directly decreased VEGF
      expression by targeting its 3'-untranslated region. Further investigation
      demonstrated the regulation of miR-410 in OS cells via VEGF. In vitro MTT assay,
      Transwell, and flow cytometry showed that transfection of the miR-410 expression
      plasmid inhibited cell proliferation and contributed to apoptosis in OS cells.
      Moreover, restoration of VEGF reversed the effect of miR-410 on OS cells, and
      upregulated the expression of phosphorylated AKT. Finally, overexpression of miR
      410 also showed a negative effect on tumor growth in vivo. Our findings suggest a
      cooperative relationship between miR-410 and VEGF in OS cell regulation. This
      information may help researchers to better understand miRNA regulation in cancer
      and provide a rationale for developing miRNA-based strategies for OS treatment.

PMID- 25385480
TI  - Identification of genes associated with the differentiation potential of adipose
      derived stem cells to osteocytes or myocytes.
AB  - Adipose-derived stem cells (ADSCs) have been considered as the optimal cells for
      regenerative medicine because ADSCs have the potential of multi-directional
      differentiation. To study the mechanisms of ADSCs differentiation, we analyzed
      microarray of GSE37329. GSE37329 was downloaded from Gene Expression Omnibus
      including 3 ADSCs, 2 ADSCs-derived osteocytes, and 2 ADSCs-derived myocytes
      samples. The differentially expressed genes (DEGs) were screened using limma
      package. Their underlying functions were predicted by gene ontology and pathway
      enrichment analyses. Besides, the interaction relationships of the proteins
      encoded by DEGs were obtained from STRING database, and protein-protein
      interaction (PPI) network was constructed using Cytoscape. Furthermore, modules
      analysis of PPI network was performed using MCODE in Cytoscape. We screened 662
      and 484 DEG separately for the ADSCs-derived osteocytes and myocytes compared
      with ADSCs. There were 205 common up-regulated and 128 common down-regulated DEGs
      between the two groups. Function enrichment indicated that these common DEGs,
      especially, VEGFA, FGF2, and EGR1 may be related to cell differentiation. PPI
      network for common DEGs also suggested that VEGFA (degree = 29), FGF2 (degree =
      17), and EGR1 (degree = 12) might be more important because they had higher
      connectivity degrees, and they might be involved in cell differentiation by
      interacting with other genes in module A (e.g., EGR1-NGF and EGR1-LEP), and B
      (e.g., VEGFA-PDGFD). Additionally, the IGF1 and BTG1 may be, respectively,
      specific for osteocytes and myocytes differentiation. VEGFA, PDGFD, FGF2, EGR1,
      NGF, LEP, IGF1, and BTG1 might serve as target genes in regulating ADSCs
      differentiation.

PMID- 25385481
TI  - Hierarchically superstructured prussian blue analogues: spontaneous assembly
      synthesis and applications as pseudocapacitive materials.
AB  - Hierarchically superstructured Prussian blue analogues (hexacyanoferrate,
      M=Ni(II) , Co(II) and Cu(II) ) are synthesized through a spontaneous assembly
      technique. In sharp contrast to macroporous-only Prussian blue analogues, the
      hierarchically superstructured porous Prussian blue materials are demonstrated to
      possess a high capacitance, which is similar to those of the conventional hybrid
      graphene/MnO2 nanostructured textiles. Because sodium or potassium ions are
      involved in energy storage processes, more environmentally neutral electrolytes
      can be utilized, making the superstructured porous Prussian blue analogues a
      great contender for applications as high-performance pseudocapacitors. 

PMID- 25385482
TI  - The prevention and treatment of obesity.
AB  - BACKGROUND: The high prevalence of obesity (24% of the adult population) and its
      adverse effects on health call for effective prevention and treatment. METHOD:
      Pertinent articles were retrieved by a systematic literature search for the
      period 2005 to 2012. A total of 4495 abstracts were examined. 119 publications
      were analyzed, and recommendations were issued in a structured consensus
      procedure by an interdisciplinary committee with the participation of ten medical
      specialty societies. RESULTS: Obesity (body-mass index [BMI] ge;30 kg/m2) is
      considered to be a chronic disease. Its prevention is especially important. For
      obese persons, it is recommended that a diet with an energy deficit of 500
      kcal/day and a low energy density should be instituted for the purpose of weight
      loss and stabilization of a lower weight. The relative proportion of
      macronutrients is of secondary importance for weight loss. If the BMI exceeds 30
      kg/m2, formula products can be used for a limited time. More physical exercise in
      everyday life and during leisure time promotes weight loss and improves risk
      factors and obesity-associated diseases. Behavior modification and behavioral
      therapy support changes in nutrition and exercise in everyday life. With respect
      to changes in lifestyle, there is no scientific evidence to support any
      particular order of the measures to be taken. Weight-loss programs whose efficacy
      has been scientifically evaluated are recommended. Surgical intervention is more
      effective than conservative treatment with respect to reduction of bodily fat,
      improvement of obesity-associated diseases, and lowering mortality. Controlled
      studies indicate that, within 1 to 2 years, a weight loss of ca. 4 to 6 kg can be
      achieved by dietary therapy, 2 to 3 kg by exercise therapy, and 20 to 40 kg by
      bariatric surgery. CONCLUSION: There is good scientific evidence for effective
      measures for the prevention and treatment of obesity.

PMID- 25385483
TI  - Approaches to ventilation in intensive care.
AB  - BACKGROUND: Mechanical ventilation is a common and often life-saving intervention
      in intensive care medicine. About 35% of all patients in intensive care are
      mechanically ventilated; about 15% of these patients develop a ventilation
      associated pneumonia. The goal of ventilation therapy is to lessen the work of
      respiration and pulmonary gas exchange and thereby maintain or restore an
      adequate oxygen supply to the body's tissues. Mechanical ventilation can be
      carried out in many different modes; the avoidance of ventilation-induced lung
      damage through protective ventilation strategies is currently a major focus of
      clinical interest. METHOD: This review is based on pertinent articles retrieved
      by a selective literature search. RESULTS: Compared to conventional lung
      protecting modes of mechanical ventilation, the modern modes of ventilation
      presented here are further developments that optimize lung protection while
      improving pulmonary function and the synchrony of the patient with the
      ventilator. In high-frequency ventilation, tidal volumes of 1-2 mL/kgBW (body
      weight) are given, at a respiratory rate of up to 12 Hz. Assisted forms of
      spontaneous respiration are also in use, such as proportional assist ventilation
      (PAV), neurally adjusted ventilatory assist (NAVA), and variable pressure-support
      ventilation. Computer-guided closed-loop ventilation systems enable automated
      ventilation; according to a recent meta-analysis, they shorten weaning times by
      32% . CONCLUSION: The currently available scientific evidence with respect to
      clinically relevant endpoints is inadequate for all of these newer modes of
      ventilation. It appears, however, that they can lower both the invasiveness and
      the duration of mechanical ventilation, and thus improve the care of patients who
      need ventilation. Randomized trials with clinically relevant endpoints must be
      carried out before any final judgments can be made.

PMID- 25385484
TI  - Put the "walker" on.

PMID- 25385485
TI  - Contradictory weight-bearing recommendations.

PMID- 25385486
TI  - In reply.

PMID- 25385488
TI  - Imaging evaluation of lymphadenopathy and patterns of lymph node spread in head
      and neck cancer.
AB  - Accurate and consistent characterization of metastatic cervical adenopathy is
      essential for the initial staging, treatment planning and surveillance of head
      and neck cancer patients. While enlarged superficial nodes may be clinically
      palpated, imaging allows identification of deeper adenopathy as well as
      clinically unsuspected pathology and thus imaging has become an integral part of
      the evaluation of most head and neck cancers patients. This review will focus on
      the evaluation of cervical adenopathy, summarizing the currently used
      nomenclature and imaging approach for determining cervical lymph node metastases
      in head and neck malignancies. The imaging-based classification, which has also
      been adopted by the American Joint Committee on Cancer, will be presented, the
      morphologic characteristics used to identify metastatic nodes will be reviewed
      and the typical nodal spread patterns of the major mucosal cancers of the head
      and neck will be examined. 

PMID- 25385489
TI  - Cyclic chlorine trap-doping for transparent, conductive, thermally stable and
      damage-free graphene.
AB  - We propose a novel doping method of graphene using the cyclic trap-doping method
      with low energy chlorine adsorption. Low energy chlorine adsorption for graphene
      chlorination avoided defect (D-band) formation during the doping by maintaining
      the pi-bonding of the graphene, which affects conductivity. In addition, by
      trapping chlorine dopants between the graphene layers, the sheet resistance could
      be decreased by ~ 88% under optimized conditions. Among the reported doping
      methods, including chemical, plasma, and photochemical methods, the proposed
      doping method is believed to be the most promising for producing graphene with
      extremely high transmittance, low sheet resistance, high thermal stability, and
      high flexibility for use in various flexible electronic devices. The results of
      Raman spectroscopy and sheet resistance showed that this method is also non
      destructive and controllable. The sheet resistance of the doped tri-layer
      graphene was 70 Omega per sq. at transmittance of 94%, and which was maintained
      for more than 100 h in a vacuum at 230  degrees C. Moreover, the defect intensity
      of graphene was not increased during the cyclic trap-doping.

PMID- 25385490
TI  - Impact of gender on success and complication rates after ureteroscopy.
AB  - PURPOSE: To investigate the impact of gender differences on treatment success,
      intraoperative and postoperative complications in patients undergoing
      ureteroscopy (URS). MATERIALS AND METHODS: A prospectively maintained database of
      927 consecutively performed ureteroscopies on solitary ureteral stones in four
      different centers was retrospectively analyzed. Stones were detected with
      preoperative computed tomography scans or intravenous urography imaging. Patients
      received intravenous antibiotics as perioperative prophylaxis. Patients with
      symptomatic urinary tract infections (UTI) prior to surgery were excluded. Follow
      up was up to 2 weeks after URS or stent removal. RESULTS: Two hundred and eighty
      six women and 641 men were included in this study. Mean stone size was 9 mm
      (range 2-35 mm). A double-J stent was placed in 240 (83 %) women and 527 (82 %)
      men at the end of surgery (p = 0.075). There was no significant gender difference
      in terms of stent dislocation (p = 0.239). Two hundred and fifty-one women (87 %)
      and 564 men (87 %) were stone-free after the first procedure (p = 0.917).
      Intraoperative complications were observed in 14 (4.8 %) women and 37 (5.9 %) men
      (p = 0.313). Severe UTI presenting with fever (>38  degrees C) and requiring
      prolonged hospitalization with parenteral antibiotics were observed in 11 (3 %)
      women and 8 (1 %) men postoperatively. This difference was statistically
      significant (p = 0.025). CONCLUSION: No significant differences between female
      and male patients harboring ureteral stones with respect to intraoperative
      complications were detected. Although stone characteristics were comparable
      between groups, a small number of women had significantly more severe UTI's
      postoperatively. Our current therapy regimen for URS seems to be efficient and
      safe both for females and males.

PMID- 25385491
TI  - Improving medication administration safety: using naive observation to assess
      practice and guide improvements in process and outcomes.
AB  - PURPOSE: To present findings from the Collaborative Alliance for Nursing
      Outcomes' (CALNOC) hospital medication administration (MA) accuracy assessment in
      a sample of acute care hospitals. Aims were as follows: (1) to describe the
      CALNOC MA accuracy assessment, (2) to examine nurse adherence to six safe
      practices during MA, (3) to examine the prevalence of MA errors in adult acute
      care, and (4) to explore associations between safe practices and MA accuracy.
      METHODS: Using a cross-sectional design, point in time, and convenience sample,
      direct observation data were collected by 43 hospitals participating in CALNOC's
      benchmarking registry. Data included 33,425 doses from 333 observation studies on
      157 adult acute care units. Results reveal that the most common MA safe practice
      deviations were distraction/interruption (22.89%), not explaining medication to
      patients (13.90%), and not checking two forms of ID (12.47%). The most common MA
      errors were drug not available (0.76%) and wrong dose (0.45%). The overall
      percentage of safe practice deviations per encounter was 11.40%, whereas the
      overall percentage of MA errors was 0.32%. CONCLUSIONS AND IMPLICATIONS: Findings
      predict that for 10,000 MA encounters, 27,630 safe practice deviations and 770 MA
      errors will occur. A 36% reduction in practice deviation per encounter prevents
      4.4% MA errors. Ultimately, reliably performing safe practices improves MA
      accuracy.

PMID- 25385492
TI  - Rehabilitation provided to patients with rheumatoid arthritis: a comparison of
      three different rheumatology clinics in Austria, Sweden and the UK from the
      perspectives of patients and health professionals.
AB  - OBJECTIVE: To explore patients' and health professionals' views of outpatient
      rehabilitation services for patients with rheumatoid arthritis in 3 different
      rheumatology sites across Europe. METHODS: A qualitative multi-method study was
      conducted with patients and health professionals in Vienna (Austria), Gothenburg
      (Sweden) and Leeds (UK). Data collection was carried out during focus groups with
      patients and health professionals. Patients' hospital records were integrated
      into the analysis. Data were analysed for site and findings were compared across
      sites. RESULTS: A total of 20 patients and 20 health professionals participated
      in 12 focus groups. Although the 3 sites were all publicly funded university
      clinics, there were differences between sites regarding the structure and content
      of rehabilitation services. The themes that emerged in the focus groups were:
      referrals; continuity in rehabilitation; information provided to patients;
      patients' organizations; documentation and communication amongst health
      professionals; interface between primary and specialist care; and prescription
      practices. Most themes were addressed at all 3 sites, but there were variations
      in the specifics within themes. CONCLUSION: Integration of patients' and health
      professionals' views on how rehabilitation services are coordinated and how
      (parts of) processes are set up elsewhere provide valuable information for the
      further optimization of rehabilitation services.

PMID- 25385493
TI  - Role of Shh and TGF in cyclosporine-enhanced expression of collagen and alpha-SMA
      by gingival fibroblast.
AB  - OBJECTIVE: Cyclosporine-A (CsA)-induced gingival overgrowth may arise from an
      alteration in stoma matrix homeostasis. Sonic hedgehog (Shh) plays a key role
      during embryogenic development and fibrotic progression, and may be involved in
      CsA-altered gingival matrix homeostasis. METHODS: Using the reverse transcription
      polymerase chain reaction and Western blot analysis, we investigated the mRNA and
      protein expressions of Shh, type 1 collagen (COL1), alpha-smooth muscle actin
      (alpha-SMA) and transforming growth factor-beta (TGF-beta) in human gingival
      fibroblasts after CsA treatments. The effect of Shh on CsA-induced alterations
      was further evaluated by the extra-supplement or inhibition of Shh or TGF-beta.
      RESULTS: Cyclosporine-A enhanced COL1, alpha-SMA, Shh and TGF-beta expressions in
      human gingival fibroblasts. The exogenous Shh/TGF-beta augmented the expression
      of COL1 and alpha-SMA, and the Shh/TGF-beta inhibition suppressed the CsA
      enhanced COL1 and alpha-SMA expressions. Moreover, Shh mRNA and protein
      expressions increased if extra-supplementing the exogenous TGF-beta, whereas the
      CsA-upregulated Shh was mitigated by the TGF-beta pathway inhibitor. However,
      neither exogenous Shh nor the Shh pathway inhibitor alters TGF-beta expression or
      CsA-up-regulated TGF-beta expression. CONCLUSIONS: Shh, regulated by TGF-beta,
      mediates CsA-altered gingival matrix homeostasis.

PMID- 25385494
TI  - Bmi1 promotes erythroid development through regulating ribosome biogenesis.
AB  - While Polycomb group protein Bmi1 is important for stem cell maintenance, its
      role in lineage commitment is largely unknown. We have identified Bmi1 as a novel
      regulator of erythroid development. Bmi1 is highly expressed in mouse erythroid
      progenitor cells and its deficiency impairs erythroid differentiation. BMI1 is
      also important for human erythroid development. Furthermore, we discovered that
      loss of Bmi1 in erythroid progenitor cells results in decreased transcription of
      multiple ribosomal protein genes and impaired ribosome biogenesis. Bmi1
      deficiency stabilizes p53 protein, leading to upregulation of p21 expression and
      subsequent G0/G1 cell cycle arrest. Genetic inhibition of p53 activity rescues
      the erythroid defects seen in the Bmi1 null mice, demonstrating that a p53
      dependent mechanism underlies the pathophysiology of the anemia. Mechanistically,
      Bmi1 is associated with multiple ribosomal protein genes and may positively
      regulate their expression in erythroid progenitor cells. Thus, Bmi1 promotes
      erythroid development, at least in part through regulating ribosome biogenesis.
      Ribosomopathies are human disorders of ribosome dysfunction, including Diamond
      Blackfan anemia (DBA) and 5q- syndrome, in which genetic abnormalities cause
      impaired ribosome biogenesis, resulting in specific clinical phenotypes. We
      observed that BMI1 expression in human hematopoietic stem and progenitor cells
      from patients with DBA is correlated with the expression of some ribosomal
      protein genes, suggesting that BMI1 deficiency may play a pathological role in
      DBA and other ribosomopathies.

PMID- 25385495
TI  - Separation and detection of plasmalogen in marine invertebrates by high
      performance liquid chromatography with evaporative light-scattering detection.
AB  - We have developed a new method for determining ethanolamine plasmalogen contents
      in marine invertebrates. This quantification method involves derivatization of
      ethanolamine glycerophospholipid (EtnGpl) subclasses, alkenylacyl (plasmalogen),
      diacyl, and alkylacyl subclasses, by enzyme treatment and acetylation, followed
      by separation and detection by high-performance liquid chromatography (HPLC) with
      evaporative light-scattering detection (ELSD). This method enabled complete
      separation of the subclasses, and the limit of detection for plasmalogen was 200
      ng (260 pmol). The peak area of plasmalogen by ELSD was unaffected by the degree
      of unsaturated fatty acids in EtnGpl, in contrast to ultraviolet (UV) detection.
      Thus, this method enables accurate determination of plasmalogen contents in
      various species containing marine products possessing abundant polyunsaturated
      fatty acids (PUFA). The method developed here was applied to marine invertebrates
      available in Japan. The examined marine invertebrates showed a wide range of
      plasmalogen contents ranging from 19 to 504 MUmol/100 g wet wt. The plasmalogen
      levels in samples except those of class Cephalopoda and Crustacea were more than
      60 mol% of EtnGpl.

PMID- 25385496
TI  - Vitamin E conditionally inhibits atherosclerosis in ApoE knockout mice by anti
      oxidation and regulation of vasculature gene expressions.
AB  - Lipid deposition in artery walls is implied in the pathogenesis of
      atherosclerosis and imbalance between uptake and efflux of cholesterol favors the
      deposition. We investigated the effect of vitamin E with the same dose and
      duration on the different stages of atherosclerosis in Apolipoprotein E knockout
      (ApoE KO) mice and explored the potential mechanisms. The results showed that the
      ApoE KO mouse spontaneously develops atherosclerosis in an age-dependent manner
      from 14 to 46 weeks on the regular chow. Vitamin E (100 mg/kg) supplementation to
      ApoE KO mice at 6, 14, and 22 weeks for 8 weeks significantly reduced the
      atherosclerotic lesion area by 41, 29 and 19% respectively compared to the age
      matched control mice; however had no significant effect on the lesion when given
      at 30 and 38 weeks. In addition, vitamin E supplemented at the ages from 6 to 30
      weeks decreased the contents of serum oxLDL and TBARS without affecting the TC
      and TAG contents in serum and liver. Furthermore, vitamin E supplemented at 6, 14
      and 22 weeks down-regulated vasculature mRNA expressions of scavenger receptor
      CD36 and up-regulated mRNA expressions of PPARgamma, LXRalpha and ABCA1 which are
      involved in reverse cholesterol transportation; however had no significant
      effects on these genes when given at 30 and 38 weeks. In conclusion, vitamin E
      with same dose and duration inhibits the early but not advanced atherosclerotic
      lesion in ApoE KO mice by anti-oxidation and regulation of mRNA expression of
      genes involved in cholesterol uptake and efflux, which favors the improvement of
      atherosclerosis.

PMID- 25385497
TI  - The role of liver stiffness measurement in the evaluation of liver function and
      esophageal varices in cirrhotic patients.
AB  - OBJECTIVE: We aimed to evaluate the efficacy of liver stiffness measurement (LSM)
      in predicting the presence and severity of esophageal varices (EV) and
      investigating its association with liver function (LF) in patients with liver
      cirrhosis. METHODS: Medical records of 90 cirrhotic patients who underwent LSM by
      transient elastography were retrospectively reviewed. The relationship between
      LSM and the presence and severity of EV was evaluated by
      esophagogastroduodenoscopy (EGD) and multislice spiral computed tomography
      (MSCT). Another 25 healthy individuals were included as controls. RESULTS: LSM
      was significantly associated with the Child-Pugh score in cirrhotic patients,
      with the highest LSM in those with Child-Pugh C. Patients with clinically
      decompensated cirrhosis had a higher LSM than those with compensated cirrhosis
      (36.75 +/- 16.54 kPa vs 17.65 +/- 10.87 kPa, P < 0.01). However, there was no
      significant difference in LSM value between patients with severe EV and those
      with no or non-severe EV determined by endoscopy (28.18 +/- 17.44 kPa vs 31.00 +/
      18.44 kPa) or MSCT (29.71 +/- 18.39 kPa vs 24.90 +/- 14.80 kPa). The diagnostic
      value of LSM for predicting severe EV was low in unselected cirrhotic patients.
      The presence of EV examined by EGD and MSCT was similar to each other.
      CONCLUSIONS: LSM could be used to evaluate the progression of liver cirrhosis
      continuously. However, its role in assessing EV grades in advanced cirrhosis
      needs further confirmation. MSCT can assess EV accurately and may serve as an
      alternative to endoscopy in the assessment of portal hypertension.

PMID- 25385499
TI  - Active systemic lupus erythematosus is associated with a reduced cytokine
      production by B cells in response to TLR9 stimulation.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease
      associated with a break in self-tolerance reflected by a production of
      antinuclear autoantibodies. Since autoantibody production can be activated via
      nucleic acid Toll-like receptor 9 (TLR9), the respective pathway has been
      implicated in the development of SLE and pathogenic B cell responses. However,
      the response of B cells from SLE patients to TLR9 stimulation remains
      incompletely characterized. METHODS: In the current study, the response of B
      cells from SLE patients and healthy donors upon TLR9 stimulation was analyzed in
      terms of proliferation and cytokine production and correlated with the lupus
      disease activity and anti-dsDNA titers. RESULTS: B cells from SLE patients showed
      a reduced response to TLR9 agonist compared to B cells from healthy donors in
      terms of proliferation and activation. B cells from SLE patients with higher
      disease activity produced less interleukin (IL)-6, IL-10, vascular endothelial
      growth factor, and IL-1ra than B cells from healthy donors. Further analyses
      revealed an inverse correlation of cytokines produced by TLR9-stimulated B cells
      with lupus disease activity and anti-dsDNA titer, respectively. CONCLUSION: The
      capacity of B cells from lupus patients to produce cytokines upon TLR9 engagement
      becomes less efficient with increasing disease activity, suggesting that they
      either enter an exhausted state or become tolerant to TLR stimulation for
      cytokine production when disease worsens.

PMID- 25385500
TI  - Hepatitis B vaccination during pregnancy for preventing infant infection.
AB  - BACKGROUND: Infant hepatitis B infection increases the risk of chronic infection,
      cirrhosis or liver cancer (hepatocellular carcinoma) in the adult. Perinatal
      transmission is a common route of infection. OBJECTIVES: To assess the
      effectiveness and adverse effects of hepatitis B vaccine administered to pregnant
      women for preventing hepatitis B virus infection in infants. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August
      2014). SELECTION CRITERIA: Randomized controlled trials (RCTs) assessing
      hepatitis B vaccination compared with placebo or no treatment during pregnancy
      for preventing infant infection. Quasi-RCTs and cross-over studies were not
      eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trials for inclusion. If any studies had been included, we
      planned to assess the risk of bias, extract data and check the data for accuracy
      of all included studies. MAIN RESULTS: We did not identify any studies for
      inclusion. AUTHORS' CONCLUSIONS: We found no RCTs that assessed the effects of
      hepatitis B vaccine during pregnancy for preventing infant infection.
      Consequently, this review cannot provide guidance for clinical practice in this
      area. However, it does identify the need for well-designed randomized clinical
      trials to assess the effect of hepatitis B vaccine during pregnancy on the
      incidence of infant infection and to determine any adverse effects.

PMID- 25385501
TI  - p38MAPK is involved in apoptosis development in apheresis platelet concentrates
      after riboflavin and ultraviolet light treatment.
AB  - BACKGROUND: Pathogen inactivation (PI) accelerates the platelet (PLT) storage
      lesion, including apoptotic-like changes. Proteomic studies have shown that
      phosphorylation levels of several kinases increase in PLTs after riboflavin and
      UV light (RF-PI) treatment. Inhibition of p38MAPK improved in vitro PLT quality,
      but the biochemical basis of this kinase's contribution to PLT damage requires
      further analysis. STUDY DESIGN AND METHODS: In a pool-and-split design, apheresis
      PLT concentrates were either treated or kept untreated with or without selected
      kinase inhibitors. Samples were analyzed throughout 7 days of storage, monitoring
      in vitro quality variables including phosphatidylserine exposure, degranulation,
      and glucose metabolism. Changes in the protein expression of Bax, Bak, and Bcl-xL
      and the activities of caspase-3 and -9 were determined by immunoblot analysis and
      flow cytometry, respectively. RESULTS: The expression levels of the proapoptotic
      proteins Bax and Bak, but not the antiapoptotic protein Bcl-xL, were
      significantly increased after the RF-PI treatment. This trend was reversed in the
      presence of p38MAPK inhibitor SB203580. As a result of increasing proapoptotic
      protein levels, caspase-3 and -9 activities were significantly increased in RF-PI
      treatment during storage compared with control (p < 0.05). Similarly, p38MAPK
      inhibition significantly reduced these caspase activities compared with vehicle
      control after RF-PI treatment (p < 0.05). CONCLUSION: These findings revealed
      that p38MAPK is involved in signaling leading to apoptosis triggered by RF-PI.
      Elucidation of the biochemical processes influenced by PI is a necessary step in
      the development of strategies to improve the PLT quality and ameliorate the
      negative effects of PI treatment.

PMID- 25385502
TI  - Interlocking-based attachment during locomotion in the beetle Pachnoda marginata
      (Coleoptera, Scarabaeidae).
AB  - The attachment function of tibial spurs and pretarsal claws in the beetle
      Pachnoda marginata (Coleoptera, Scarabaeidae) during locomotion was examined in
      this study. First, we measured the angle, at which the beetles detached from
      substrates with different roughness. At a surface roughness of 12 MUm and higher,
      intact animals were able to cling to a completely tilted platform (180 degrees ).
      Second, we estimated the forces the beetles could exert in walking on smooth and
      rough cylinders of different diameters, on a plane and also between two plates.
      To elucidate the role of the individual structures, we ablated them
      consecutively. We found tibial spurs not to be in use in walking on flat
      substrates. On some of the curved substrates, ablation of tibial spurs caused an
      effect. A clear effect of tibial spurs was revealed in walking between two
      plates. Thus, these structures are probably used for generating propulsion in
      narrowed spaces.

PMID- 25385503
TI  - Chemistry of group 9 dimetallaborane analogues of octaborane(12).
AB  - We report the synthesis, isolation and structural characterization of several
      moderately air stable nido-metallaboranes that represent boron rich open cage
      systems. The reaction of [Cp*CoCl]2, (Cp* = eta(5)-C5Me5), with [BH3.thf] in
      toluene at ice cold temperature, followed by thermolysis in boiling toluene
      produced [(Cp*Co)B9H13], 1 [(Cp*Co)2B8H12], 2 and [(Cp*Co)2B6H10] 3. Building
      upon our earlier reactivity studies on rhodaboranes, we continue to explore the
      reactivity of dicobalt analogues of octaborane(12) cluster 3 with [Fe2(CO)9] and
      [Ru3(CO)12] at ambient conditions that yielded novel fused clusters
      [Fe2(CO)6(Cp*Co)2B6H10], 4 and [Ru4(CO)11(Cp*Co)2B3H3], 5 respectively. In an
      attempt to synthesize a heterometallic metallaborane compound we performed the
      reaction of [(Cp*Rh)2B6H10], 6 with [Cp*IrH4] that yielded a Ir-Ir double bonded
      compound [(Cp*Ir)2H3][B(OH)4], 7. All the new compounds have been characterized
      by IR, (1)H, (11)B, (13)C NMR spectroscopy, and the molecular structures were
      unambiguously established by X-ray diffraction analysis. 

PMID- 25385504
TI  - Elevated levels of pentraxin 3 in systemic sclerosis: associations with vascular
      manifestations and defective vasculogenesis.
AB  - OBJECTIVE: To clarify the role of pentraxin 3 (PTX3), a multifunctional pattern
      recognition protein that can suppress fibroblast growth factor 2 (FGF-2), in
      systemic sclerosis (SSc)-related vasculopathy. METHODS: We assessed 171 SSc
      patients and 19 age- and sex-matched healthy control subjects. Circulating PTX3
      and FGF-2 levels were measured by enzyme immunoassay, and CD34+CD133+CD309+
      endothelial progenitor cells (EPCs) were counted by flow cytometry. Correlations
      between PTX3 and FGF-2 and the presence or future development of vascular
      manifestations, including digital ulcers and pulmonary arterial hypertension
      (PAH), were identified by univariate and multivariate analysis. The effect of
      PTX3 on EPC differentiation was evaluated in proangiogenic cultures of mouse bone
      marrow cells in combination with colony formation assay. RESULTS: Circulating
      PTX3 and FGF-2 levels were significantly higher in SSc patients than in healthy
      control subjects. PTX3 was elevated in SSc patients who had digital ulcers or
      PAH, while FGF-2 was reduced in SSc patients with PAH. Multivariate analysis
      identified elevated PTX3 as an independent parameter associated with the presence
      of digital ulcers and PAH, and PTX3 levels were a useful predictor of future
      occurrences of digital ulcers. Reduced FGF-2 was independently associated with
      the presence of PAH. EPC counts were significantly lower in patients with digital
      ulcers or PAH and correlated negatively with circulating PTX3 concentrations.
      Finally, PTX3 inhibited EPC differentiation in vitro. CONCLUSION: In SSc
      patients, exposure to high concentrations of PTX3 may suppress EPC-mediated
      vasculogenesis and promote vascular manifestations such as digital ulcers and
      PAH.

PMID- 25385506
TI  - Resveratrol exerts an anti-apoptotic effect on human bronchial epithelial cells
      undergoing cigarette smoke exposure.
AB  - Cigarette smoke can cause endoplasmic reticulum stress and induce apoptosis, both
      of which are important pathogenic factors contributing to chronic obstructive
      pulmonary disease. The aim of the present study was to produce a cigarette smoke
      extract (CSE)-induced apoptosis human bronchial epithelial cell (HBEpC) model, to
      investigate the protective effects of resveratrol (RES). The role of oxygen
      regulated protein 150 (ORP150) in the RES-induced activation of Sirtuin 1 (SIRT1)
      was additionally studied. Cultured HBEpCs were initially treated with CSE to
      induce apoptosis, followed by an incubation either with or without RES. Numerous
      techniques were used to evaluate the outcomes of the present study, including
      cell counting kit-8 assay, quantitative polymerase chain reaction, western
      blotting, Hoechst 33342 staining and AnnexinV-PI flow cytometry apoptosis
      analyses, and gene knockdown. It was identified that 24 h 2% CSE incubation
      induced apoptosis in HBEpC, accompanied by an overexpression of the apoptosis
      molecular markers CCAAT-enhancer-binding protein homologous protein, caspase 4
      and caspase 3. Pre-treatment of the cells with RES markedly alleviated the
      severity of apoptosis, as confirmed by apoptosis analyses and the expression
      levels of the apoptosis molecular markers. SIRT1 was shown to be overexpressed
      following RES treatment. However, following the gene knockdown of ORP150, the
      anti-apoptotic effects of RES were significantly attenuated. The results of the
      present study demonstrate that RES may have a protective effect against CSE
      induced apoptosis, and a molecular pathway involving SIRT1 and ORP150 may be
      associated with the anti-apoptotic functions of RES in HBEpC.

PMID- 25385508
TI  - High variability of clinical symptoms in a Polish family with a novel THAP1
      mutation.
AB  - BACKGROUND: Mutations in the THAP1 gene are associated with a broad spectrum of
      dystonia including focal and generalized forms. Missense, nonsense and frameshift
      mutations, including small insertions/deletions within the THAP1 gene, have been
      reported and majority of them cause autosomal dominant disease with limited
      penetrance of approximately 60%. Here, we describe a novel THAP1 mutation.
      MATERIALS AND METHODS: Blood samples were collected from consenting family
      members for extraction of genomic DNA. As controls, we analyzed 150 individuals
      without neurological disorders. THAP1 coding sequences were amplified with PCR
      and sequenced. RESULTS: We describe a Polish family with a novel heterozygous
      substitution: c.167A>G (p.Glu56Gly) in THAP1 exon 2. This is the largest reported
      family with the mutation in THAP1 exon 2. The mutation was found in four of five
      genetically studied family members, including two clinically affected male
      individuals and two asymptomatic carriers (male and female). Data on one deceased
      male symptomatic subject were available and two assumed carriers were identified.
      The substitution was not present in any of the analyzed healthy controls. The
      high variability of phenotype included age of onset, localization of the initial
      symptom as well as the rate and degree of generalization. CONCLUSIONS: Our
      findings strongly suggest the role of other genetic factors or environmental
      triggers in the pathogenesis of dystonia related to mutations in THAP1 gene.

PMID- 25385507
TI  - Atg23 and Atg27 act at the early stages of Atg9 trafficking in S. cerevisiae.
AB  - Atg9 is a conserved multipass transmembrane protein with an essential role in
      autophagy. In Saccharomyces cerevisiae, it travels through the secretory pathway
      to a unique compartment, the Atg9 peripheral structures. These structures are
      then targeted to the phagophore assembly site (PAS), where they are proposed to
      help deliver membrane to the forming autophagosome. We used 'in vivo
      reconstitution' of this process in a multiple-knockout strain to define four
      proteins, Atg11, Atg19, Atg23 and Atg27, as the core minimal machinery necessary
      and sufficient for the trafficking of Atg9 to the PAS. Atg23 and Atg27 function
      in the formation of the Atg9 peripheral structures. Overexpression of Atg9 can
      bypass the need for Atg23, suggesting that the amount of Atg9 in each peripheral
      structure is a critical factor in their targeting to the PAS. In contrast,
      overexpression of Atg23 or Atg27 interferes with Atg9 trafficking, suggesting
      that these proteins must be present in the appropriate stoichiometry in order to
      function properly. These data allow us to resolve existing controversies
      regarding the role of Atg23 and Atg27, and propose a model that ties together
      previous observations regarding the role of Atg9 in autophagosome formation. 

PMID- 25385509
TI  - Vascular risk factors and Alzheimer's disease.
AB  - Vascular factors are now established risk factors for cognitive decline, both for
      dementia and its two main subtypes: Alzheimer's disease (AD) and vascular
      dementia. Their impact likely goes beyond causing an increase in concurrent
      vascular pathology, since they have been associated with increasing the risk of
      degenerative Alzheimer (plaque and tangle) pathology, either by increasing its
      rate of formation or reducing elimination from the brain, or a mixture of the
      two. A comprehensive series of reviews published in BMC Medicine, investigates
      the relationship between AD and cardiovascular diseases and risk factors from a
      clinical, pathological and therapeutic perspective. Whilst links between vascular
      factors and AD have clearly been demonstrated at both the clinical and
      pathological level, the nature of the relationship remains to be fully
      established and there is a lack of high quality treatment studies examining the
      extent to which vascular risk modification alters AD disease course. Further
      longitudinal mechanistic and therapeutic studies are required, especially to
      determine whether treatment of vascular risk can prevent or delay the onset of AD
      and/or reduce its rate of clinical progression. 

PMID- 25385510
TI  - Black cat in a dark room: the absence of a directly oncogenic virus does not
      eliminate the role of an infectious agent in cutaneous T-cell lymphoma
      pathogenesis.

PMID- 25385511
TI  - Lean mass as a total mediator of the influence of muscular fitness on bone health
      in schoolchildren: a mediation analysis.
AB  - This report aims to analyse the independent association of lean mass and muscle
      fitness with bone mineral content (BMC) and bone mineral density (BMD), and to
      examine whether the relationship between muscle fitness and bone health is
      mediated by lean mass. Body composition (by dual energy X-ray absorptiometry
      (DXA)), muscle fitness, physical activity, age and height were measured in 132
      schoolchildren (62 boys, aged 8-11 years). Analysis of covariance tested
      differences in bone-related variables by lean mass and muscle fitness,
      controlling for different sets of confounders. Linear regression models fitted
      for mediation analyses examined whether the association between muscle fitness
      and bone mass was mediated by lean mass. Children with good performance in
      handgrip and standing long jump had better and worse bone health, respectively.
      These differences disappeared after controlling for lean mass. Children with high
      lean mass had higher values in all bone-related variables. In addition, the
      relationship between muscle fitness and bone mass was fully mediated by lean
      mass. In conclusion, the relationship between upper-limbs muscle fitness and bone
      health seems to be dependent on lean mass but not on muscle fitness.
      Schoolchildren with high lean mass have more BMC and BMD in all regions. Lean
      mass mediates the association between muscle fitness and bone mass.

PMID- 25385512
TI  - Release, transport and toxicity of engineered nanoparticles.
AB  - Recent developments in nanotechnology have facilitated the synthesis of novel
      engineered nanoparticles (ENPs) that possess new and different physicochemical
      properties. These ENPs have been ex tensive ly used in various commercial sectors
      to achieve both social and economic benefits. However. the increasing production
      and consumption of ENPs by many different industries has raised concerns about
      their possible release and accumulation in the environment. Released EN Ps may
      either remain suspended in the atmosphere for several years or may accumulate and
      eventually be modified int o other substances. Settled nanoparticles can he
      easily washed away during ra in s. and therefore may easily enter the food chain
      via water and so il. Thus. EN Ps can contaminate air. water and soil and can
      subsequently pose adverse risks to the health of different organisms. Studies to
      date indicate that ENP transport to and within the ecosystem depend on their
      chemical and physical properties (viz .. size. shape and solubility) . Therefore.
      the EN Ps display variable behavior in the environment because of their
      individual properties th at affect their tendency for adsorption, absorption,
      diffusional and colloidal interaction. The transport of EN Ps also influences
      their fate and chemical transformation in ecosystems. The adsorption, absorption
      and colloidal interaction of ENPs affect their capacity to be degraded or
      transformed, whereas the tendency of ENPs to agglomerate fosters their
      sedimentation. How widely ENPs are transported and their environmental fate
      influence how tox ic they may become to environmental organisms. One barrier to
      fully understanding how EN Ps are transformed in the environment and how best to
      characterize their toxicity, is related to the nature of their ultrafine
      structure. Experiments with different animals, pl ants, and cell lines have
      revealed that ENPs induce toxicity via several cellular pathways that is linked
      to the size. shape. surface area, agglomeration state. and sur face charge of the
      ENP involved. Future research is needed to elucidate the mechanisms by which
      nanoparticles act to induce their tox ic effects aft er they reach various
      ecosystems. Moreover. work is needed to develop a holistic approach for better
      understanding the effects that ENPs produce at the cellular and genetic level.

PMID- 25385513
TI  - Source characterization of polycyclic aromatic hydrocarbons by using their
      molecular indices: an overview of possibilities.
AB  - In recent decades. an exponential increase in the concentration of anthropogenic
      Polycyclic Aromatic Hydrocarbons (PAHs; see Table I for a li st of PAH
      abbreviations) has been observed worldwide. Regulators need to know the sources
      if concentrations are to be reduced and appropriate remediation measures taken.
      "Source characterization of PAHs" involves linking these contaminants to their
      sources. Scientists place PAH sources into three classes: pyrogenic, petrogenic.
      and natural. In this review. we investigate the possibility of using PAH
      molecular ratios individually or in combination for the purpose of deducing the
      petrogenic or pyrogenic origin of the contamination in sediments. We do this by
      reviewing the characteristic PAH patterns of the sources and by taking into
      account the fate of PAHs in the aquatic environment. Many PAH indicators have
      been developed for the purpose of discriminating different PAH sources. In Table
      4 we summarize the applicability of different PAH ratios and threshold values.
      The analysis of two- to four-ringed alkylated PAH soilers the possibility to
      distinguish two or more single sources or categories of pollution in greater
      detail. For example. the FLO/PYO. the PPI. and PO/AO ratios can be used to
      discriminate between pyrogenic and petrogcnic sources of contamination. When
      petrogenic contamination is suspected. chrysenes. PAHs lighter than CO. and in
      particular. alkylated PAHs can usually be of use. For unburned coal PAHs. The
      methylphenanthrenic ratios (MP!s). the 1-D I/4- DI. and BbF/BkF are promising,
      since they are sometimes correlated with vitrinite rellectance (coal ranks).
      Alkylphenanthrenes can be used to detect biomass combustion. Higher molecular
      weight parent and alkylated PAHs are appropriate for pyrogenic discriminations.
      When PAH indices are coupled with discriminant analysis techniques such as PMF
      (positive matrix factorization),the origin of multiple sources in even the most
      complex environments can be traced and measured. Even so. the most stable isomer
      pairs degrade differentially. depending on their thermodynamic stability, the
      environmental conditions, and the type of degradation. If PAH ratios are to be
      used, it is usually necessary to have pri or knowledge of the degradation state
      of the matrices examined (air, sediment, etc.) and of how the PAH ratio behaves
      under such conditions. PAH ind ices (e.g ., NO/CO or LPAH/HPAH ) can be app lied
      for distinguishing differential degradation gradients (photodegradation,
      biodegradation, etc.). Degradation does not significantly affect the ratio of
      parent to alkylated PAHs and the PI. The degradation arrow in Table 4 and Figs.
      9. I 0. II . 12. 13, 14. 15. 17. 18. 19, 20, 2 1, 22. 23. and 24 shows how the
      ratio usually changes with degradation. Merely detecting the six PAHs of Borneff6
      is not enough to establish petrogenic contamination, because Borneff6 includes
      main ly HMW PAHs. The LPAH 16 appears to be the most suitable for identify ing
      pyrogenic and petrogenic sources. For more specific information on sources and
      their discrimination it is recommended to further take into account important
      parent PAHs such as NO. BeP. PER. DO. and-most importantly- alkylatcd PAHs.

PMID- 25385514
TI  - Respiratory and cardiovascular effects of metals in ambient particulate matter: a
      critical review.
AB  - In this review, we critically evaluated the epidemiological and toxicological
      evidence for the role of specific transition metals (As. Cr. Cu. Fe. Mn. Ni. Sc.
      Ti. V and Zn) in causing or contributing to the respiratory and cardiovascular
      health effects associated with ambient PM. Although the epidemiologic studies arc
      suggestive. and both the in vivo and in vitro laboratory studies document the
      toxicity of specific metals (Fe. Ni. V and Zn). the overall weight of evidence
      does not convincingly implicate metals as major contributors to health effects.
      None of the epidemiology studies that we reviewed conclusively implicated
      specific transition metals as having caused the respiratory and cardiovascular
      effects associated with ambient levels of PM. However, the studies reviewed
      tended to be internal ly consistent in identifying some metals (Fe, Ni, V and Zn)
      more frequently than others (As, Cu, Mn and Sc) as having positive associations
      wi th health effects. The major problem wi th which the epidemiological studies
      were faced was classifying and quantifying exposure. Community and population
      exposures to metals or other components of ambient PM were inferred from
      centrally- located samplers that may not accurately represent individual level
      exposures. Only a few authors reported findings that did not support the stated
      premise of the study; indeed, statistic ally significant associations are not
      necessarily biologically significant. It is likely that .'negative studies" are
      under-represented in the published literature, making it a challenge to achieve a
      balanced evaluation of the role of metals in causing health effects associated
      with ambient PM. Both the in vivo and in vitro study results demonstrated that
      individual metals (Cu. Fe. Ni. V and Zn) and extracts of metals from ambient PM
      sources can produce acute inflammatory responses. However. the doses administered
      to laboratory animals were many orders of magnitude greater than what humans
      experience from breathing ambient air. The studies that used intratracheal
      instillation have the advantage of delivering a known dose to a specific
      anatomical location. but arc not analogous to an inhaled dose that is distributed
      over the surface area of the respiratory tract. Studies. in which laboratory
      animals or human volunteers inhaled CAPs best represent exposures to the general
      human population. The in vivo and in vitro studies reviewed provide indications
      that the probable mechanisms involved in the respiratory and cardiac effects from
      high metal exposures include: an inflammatory response mediated by formation of
      ROS, upregulation of genes coding for inflammatory cytokines, altered expression
      of genes involved in cell signaling pathways and maintenance of metals
      homeostasis.The fact that doses of metals many orders of magnitude greater than
      those existing in ambient air were required to produce measurable adverse effects
      in animals makes it doubtful that metals play any major role in respiratory and
      cardiovascular effects produced from human exposure to ambient PM. We suggest
      that future research priorities should focus on testing at more environmentally
      relevant exposure levels and that any new toxicological studies be written to
      include dosages in units that can be easily compared to human exposure levels.

PMID- 25385515
TI  - A bambusuril macrocycle that binds anions in water with high affinity and
      selectivity.
AB  - Synthetic receptors that function in water are important for the qualitative and
      quantitative detection of anions, which may act as pollutants in the environment
      or play important roles in biological processes. Neutral receptors are
      particularly appealing because they are often more selective than positively
      charged receptors; however, their affinity towards anions in pure water is only
      in range of 1-10(3)  L mol(-1) . The anion-templated synthesis of a water-soluble
      bambusuril derivative is shown to be an outstanding receptor for various
      inorganic anions in pure water, with association constants of up to 10(7)  L mol(
      1) . Furthermore, the macrocycle discriminates between anions with unprecedented
      selectivity (up to 500 000-fold). We anticipate that the combination of
      remarkable affinity and selectivity of this macrocycle will enable the efficient
      detection and isolation of diverse anions in aqueous solutions, which is not
      possible with current supramolecular systems. 

PMID- 25385516
TI  - Syntheses, crystal structures, resistivity studies, and electronic properties of
      three new barium actinide tellurides: BaThTe4, BaUTe4, and BaUTe6.
AB  - The three new solid-state compounds BaThTe4, BaUTe4, and BaUTe6 have been
      synthesized and characterized. BaThTe4 and BaUTe4 are isostructural. The
      structure consists of infinite infinity(2)[AnTe4(2-)] layers separated by Ba(2+)
      ions. Each An (An = Th, U) atom is coordinated to eight Te atoms in a bicapped
      trigonal-prismatic arrangement. Te atoms are connected to each other to form
      linear infinite chains. These Te-Te interactions are longer than that of a Te-Te
      single bond. However, this structure also possesses Te-Te single bonds. Charge
      balance in the formula BaAnTe4 may be achieved with [Ba(2+)]2[(An(4+))2(Te(2
      ))2(Te2(2-))(Te2(3-))2](4-). The structure of BaUTe6 features one-dimensional
      anionic infinity(1)[UTe6(2-)] chains that are separated by Ba(2+) ions. There are
      three Te-Te single bonds around each U atom. The anion in this structure can thus
      be described as [U(4+)(Te2(2-))3](2-). Resistivity measurements on single
      crystals of BaThTe4 and BaUTe6 show semiconducting behavior. DFT calculations
      indicate finite band gaps for BaThTe4 and for BaUTe6, whereas BaUTe4 has a
      vanishing density of states at the Fermi level.

PMID- 25385517
TI  - Association of the paired box 2 gene polymorphism with the susceptibility and
      pathogenesis of Henoch-Schonlein purpura in children.
AB  - The present study aimed to investigate the distribution of paired box 2 (PAX2)
      gene polymorphisms in healthy populations and in patients with Henoch-Schonlein
      purpura (HSP), focusing on the association between PAX2 gene polymorphisms and
      the susceptibility and clinical characteristics of HSP. Genomic DNA was extracted
      from the peripheral venous blood of 100 healthy children (mean age: 5 +/- 1.9
      years) and 118 children with HSP (mean age: 10.2 +/- 2.3 years). Polymerase chain
      reaction (PCR) was used to amplify exons 1-12 of the PAX2 gene. Denaturing high
      performance liquid chromatography and DNA sequencing analysis were conducted for
      screening of mutations in the PAX2 gene in the PCR products. No genetic
      polymorphism of the PAX2 gene was identified in exons 1-7, 9, 10 or 12. Two
      single nucleotide polymorphisms (SNPs), which presented as complete linkage
      haplotype 798C>T/909A>C, were identified in exon 8. An SNP (1164T>A) was also
      identified in exon 11. No significant difference in the allele and genotype
      frequency distribution of exon 8 (798C>T) or 11 (1164T>A) of the PAX2 gene was
      identified between the HSP and control groups (P>0.05). However, the frequency of
      the PAX2 heterozygous genotype 798C>T in the HSP with nephritis (HSPN) group was
      significantly higher than those in the controls and in the HSP without nephritis
      group (P<0.05). Furthermore, no significant correlation was identified between
      the PAX2 gene exon 8 polymorphism (798 C>T) and the renal pathology of children
      with HSPN. An SNP (1164T>A) was identified in exon 11. The PAX2 heterozygous
      genotype 798C>T did not increase susceptibility to HSP, however, it may be used
      clinically as a screening indicator for HSP in children with a high risk of renal
      involvement.

PMID- 25385518
TI  - Rapid prototyped sutureless anastomosis device from self-curing silk bio-ink.
AB  - Sutureless anastomosis devices are designed to reduce surgical time and
      difficulty, which may lead to quicker and less invasive cardiovascular
      anastomosis. The implant uses a barb-and-seat compression fitting composed of one
      male and two female components. The implant body is resorbable and capable of
      eluting heparin. Custom robotic deposition equipment was designed to fabricate
      the implants from a self-curing silk solution. Curing did not require deleterious
      processing steps but devices demonstrated high crush resistance, retention
      strength, and leak resistance. Radial crush resistance is in the range of metal
      vascular implants. Insertion force and retention strength of the anastomosis was
      dependent on fit sizing of the male and female components and subsequent vessel
      wall compression. Anastomotic burst strength was dependent on the amount of
      vessel wall compression, and capable of maintaining higher than physiological
      pressures. In initial screening using a porcine implant, the devices remained
      intact for 28 days (the length of study). Histological sections revealed cellular
      infiltration within the laminar structure of the male component, as well as at
      the interface between the male and female components. Initial degradation and
      absorption of the implant wall were observed. The speed per anastomosis using
      this new device was much faster than current systems, providing significant
      clinical improvement.

PMID- 25385519
TI  - Olfactory acuity in chronic migraine: a cross-sectional study.
AB  - OBJECTIVE/BACKGROUND: This study aims to measure olfactory acuity in chronic
      migraine subjects, at baseline and on migraine days, and compare to age- and sex
      matched controls. Olfactory impairment is common in neurological disorders. While
      smell hypersensitivity has been established with chronic migraine, olfactory
      acuity has not been well studied. METHODS: We recruited 50 subjects with chronic
      migraine from the Jefferson Headache Center and 50 age- and sex-matched controls.
      Using the University of Pennsylvania Smell Identification Test (UPSIT), a
      validated test of olfaction, olfactory acuity was measured at baseline and during
      a migraine for subjects, and compared to controls at baseline and at home 2 weeks
      later. All subjects were additionally screened for odor sensitivity and
      allodynia. RESULTS: The mean UPSIT score for migraine subjects was 34.5 on non
      migraine days and 34.7 on migraine days (mean difference=-0.4, 95% confidence
      interval [CI; -1.3, 0.6] P=.45). Controls had a mean of 35.9 and 36.1 for each
      test day (mean difference = -0.1, 95% CI [-0.9, 0.7] P=.87). On average,
      migraineurs performed worse than their matched control counterparts in both test
      sittings (test 1: P=.047; test 2: P=.01). The great majority of subjects were
      allodynic (42/50) compared with only 9 of 50 controls, and the majority of
      subjects (41/50) found more than one listed odor to be bothersome, compared with
      only 10/50 controls. On non-migraine days, 18/48 chronic migraine subjects had
      abnormal olfaction and on migraine days 14/42 had abnormal olfaction, compared
      with only 9/50 controls who had abnormal olfaction on their first UPSIT.
      CONCLUSIONS: While chronic migraine patients do not appear to have a significant
      change in olfactory acuity between migrainous and non-migrainous periods, they do
      appear to be more likely to have abnormal olfactory acuity at baseline compared
      to age- and sex-matched controls.

PMID- 25385520
TI  - Time to event analysis in the presence of competing risks.

PMID- 25385521
TI  - Does guilt mediate the association between tonic immobility and posttraumatic
      stress disorder symptoms in female trauma survivors?
AB  - Tonic immobility (TI) is an involuntary freezing response that can occur during a
      traumatic event. TI has been identified as a risk factor for posttraumatic stress
      disorder (PTSD), although the mechanism for this relationship remains unclear.
      This study evaluated a particular possible mechanism for the relationship between
      TI and PTSD symptoms: posttraumatic guilt. To examine this possibility, we
      assessed 63 female trauma survivors for TI, posttraumatic guilt, and PTSD symptom
      severity. As expected, the role of guilt in the association between TI and PTSD
      symptom severity was consistent with mediation (B = 0.35; p < .05). Thus, guilt
      may be an important mechanism by which trauma survivors who experience TI later
      develop PTSD symptoms. We discuss the clinical implications, including the
      importance of educating those who experienced TI during their trauma about the
      involuntary nature of this experience. 

PMID- 25385522
TI  - An fMRI study of face encoding and recognition in first-episode schizophrenia.
AB  - BACKGROUND: Schizophrenia has been associated with limited abilities to interact
      effectively in social situations. Face perception and ability to recognise
      familiar faces are critical for social interaction. Patients with chronic
      schizophrenia are known to show impaired face recognition. Studying first-episode
      (FE) patients allows the exclusion of confounding effects of chronicity,
      medication and institutionalisation in this deficit. OBJECTIVE: To determine
      brain (dys)functions during a face encoding and recognition paradigm in FE
      schizophrenia. METHODS: Thirteen antipsychotic-naive FE schizophrenia patients
      and 13 age- and sex-matched healthy controls underwent functional magnetic
      resonance imaging during a face encoding and recognition paradigm. Behavioural
      responses were recorded on line. RESULTS: Patients recognised significantly fewer
      of previously presented faces than the controls (p = 0.008). At the neural level,
      both groups activated a network of regions including the fusiform area,
      occipital, temporal and frontal regions. In brain activity, the two groups did
      not differ in any region during encoding or recognition conditions (p > 0.05,
      corrected or uncorrected). CONCLUSIONS: Our findings show impaired face
      recognition without a significant alteration of related brain activity in FE
      schizophrenia patients. It is possible that neural changes become more strongly
      evident with progression of the illness, and manifest themselves as behavioural
      impairments during the early course.

PMID- 25385523
TI  - Association of unipolar depression with gene polymorphisms in the serotonergic
      pathways in Han Chinese.
AB  - OBJECTIVE: The present study aims to investigate the association of unipolar
      depression (UPD) with six serotonergic gene polymorphisms in Han Chinese.
      METHODS: One hundred and thirty-two UPD patients and 180 healthy controls were
      genotyped for polymorphisms of six serotonergic genes, including tryptophan
      hydroxylase (TPH1 A218C), serotonin transporter promoter region (5-HTTLPR),
      serotonin receptor 2A (5-HT2AR -1438G/A), serotonin receptor 2C (5-HT2CR
      Cys23Ser), serotonin receptor 6 (5-HT6R C267T) and serotonin receptor 1Dbeta (5
      HT1DbetaR T371G). Symptomatic clusters were evaluated by the 24-item Hamilton
      Rating Scale for Depression (HAMD). RESULTS: The frequencies of S/S genotype and
      S allele in 5-HTTLPR polymorphism were significantly higher in UPD patients than
      in healthy controls. There was a significant difference in distributions of
      genotypes in 5-HT2CR Cys23Ser polymorphism between UPD patients and control
      subjects, but the difference became no significant when the data were further
      stratified by gender. The patients with genotypes G/G and T/G of 5-HT1DbetaR
      T371G polymorphism had significantly lower scores of diurnal variation evaluated
      by HAMD than those with genotype T/T, while the patients with genotype T/G had
      significantly higher scores of hopelessness than those with genotypes G/G and
      T/T. There were no significant differences in genotypic and allelic distributions
      of TPH1 A218C, 5-HT2AR -1438G/A or 5-HT6R C267T polymorphisms between the case
      and control groups. CONCLUSION: The study demonstrates that 5-HTTLPR and 5-HT2CR
      Cys23Ser polymorphisms might contribute to susceptibility of UPD, and the
      genotype T/T in 5-HT1DbetaR T371G polymorphism might be a risk factor for diurnal
      variation, while T/G might be a protective factor against hopelessness in Han
      Chinese populations.

PMID- 25385524
TI  - Neuropsychiatric symptoms and immune activation in patients with genital herpes.
AB  - OBJECTIVE: Neuropsychiatric disturbances are common among patients with genital
      herpes simplex virus (HSV) infection. To date, no studies have examined the
      possible role of immune activation in the aetiology of these disturbances. The
      aim of this study was to examine the relationship between markers of immune
      activation and measures of emotional and somatic dysfunction among patients with
      symptomatic genital herpes. METHODS: Twenty-two patients with documented genital
      herpes were assessed when herpetic lesions were present and when they were not.
      Each assessment included a clinical examination, self-reported symptom measures
      as well as a blood and urine collection. Markers of immune activation [neopterin
      and interleukin (IL)-6] in serum and urine were quantified by enzyme-linked
      immunoassay. These measures were also obtained from a group of healthy control
      subjects. RESULTS: Urine, but not serum, levels of neopterin and IL-6 correlated
      significantly with measures of reported psychological distress and fatigue. These
      associations were not confined to periods of overt clinical lesions. CONCLUSIONS:
      HSV-related neuropsychiatric morbidity correlates selectively with regional, but
      not systemic, measures of immune activation. We hypothesise that communication
      between the local inflammatory site in the pelvis and the brain occurs through
      autonomic afferent pathways.

PMID- 25385525
TI  - Delayed-onset delirium tremens - a diagnostic and management challenge.
AB  - BACKGROUND: Delirium tremens (DT) is one of the most serious complications of
      alcohol withdrawal, affecting 5-10% of in-patients with a mortality rate up to
      15%. DT, characterised by delirium and tremors, appears within 48-72 h of
      abstinence and persists for about 5-10 days. CASE PRESENTATION: We report a case
      of DT in a young man with delayed onset on the 15th day after the cessation of
      alcohol use, despite an uncomplicated detoxification with benzodiazepine
      treatment. CONCLUSION: We hypothesise that the intake of country liquor in our
      patient, which contains higher percentages of alcohol, causes a prolonged
      imbalance of N-methyl-d-aspartic acid and glutamate receptor activity, leading to
      the picture of delayed-onset DT and that an atypical presentation at the time of
      admission and atypicality in early course are clinical pointers to the subsequent
      development of delayed-onset DT.

PMID- 25385526
TI  - Rotator cuff-quality of life scale: adaptation to Turkish.
AB  - PURPOSE: The adaptation of scales to the native language and cultural setting of
      the patient is essential for obtaining more reliable results in scientific
      studies. In this study, the rotator cuff-quality of life scale (RC-QoLS) was
      translated into Turkish, and validity and reliability testing was performed on
      the scale. METHODS: The scale was first translated into Turkish and then from
      Turkish to English by another language specialist. Subsequently, the two
      translations were evaluated by two orthopaedic surgeons who had comprehensive
      knowledge of English to create the final Turkish version of RC-QoLS. The scale
      was used for the assessment of 54 patients (average age 56 years) with rotator
      cuff tear scheduled for surgery. The scale was completed by each patient two
      times with 1-week interval. RESULTS: The Cronbach's alpha coefficients ranged
      between 0.895 and 0.980 and intraclass correlation coefficients ranged between
      0.807 and 0.976, this rendered all domains reliable. The scale gave results very
      near to those obtained by the original questionnaire with respect to the
      constructed validity and internal consistency as well as domain relationships.
      CONCLUSIONS: In general, the Turkish version of the RC-QoLS is a valid and
      reliable test with high differentiating power that may be used in the evaluation
      the quality of life of patients with RC tear in patients who are native Turkish
      speaker. The use of the Turkish version of RC-QoLS may contribute to the making
      of a more reliable evaluation in the studies on RC problems in the Turkish
      society.

PMID- 25385527
TI  - Comparison of open acromioplasty, arthroscopic acromioplasty and physiotherapy in
      patients with subacromial impingement syndrome: a prospective randomised study.
AB  - PURPOSE: To compare the results two to three years after intervention, using
      either surgical or non-operative treatment. METHODS: Eighty-seven patients with
      subacromial impingement syndrome (SAIS) were randomised into open acromioplasty
      (OS group), arthroscopic acromioplasty (AS group) or physiotherapy (PT group)
      treatment. The assessments comprised the Constant score, the Watson and Sonnabend
      score, the SF-36 evaluation and a clinical examination performed by an
      independent observer. Fifty-five patients attended the clinical follow-up.
      RESULTS: The groups were comparable at baseline in terms of demographics and
      clinical assessments. No significant differences in terms of the clinical
      assessments or health-related quality of life (QoL) were found between the study
      groups at follow-up. The Constant score had improved significantly at follow-up
      in both the OS group and the AS group (p = 0.003 and 0.008, respectively). At
      follow-up, the OS group revealed improved strength compared with before
      intervention (p = 0.012). All groups revealed a significantly improved internal
      rotation (OSG p = 0.01, ASG p = 0.005, PTG p = 0.004). The SF-36 was
      significantly improved in some scales within all three groups. The Watson and
      Sonnabend score was significantly improved in 12/14 questions for the OS group,
      in 5/14 questions for the AS group and in 6/14 for the PT group (p < 0.02 OS
      group vs. AS group, p < 0.05 OS group vs. PT group). CONCLUSION: In this
      randomised study, the Constant score, other clinical assessments and subjective
      health-related QoL revealed no significant differences between the 3 groups two
      to three years after intervention in patients with SAIS. The OS group showed a
      greater improvement over time. LEVEL OF EVIDENCE: CT with low follow-up rate,
      Level II.

PMID- 25385528
TI  - Endoscopic ultrasound-guided pancreatic duct drainage.
AB  - Endoscopic ultrasound (EUS) has evolved from a purely diagnostic procedure to one
      with therapeutic capabilities. One of the most challenging therapeutic
      intervention for endosonographers is EUS-guided pancreatic drainage. The
      development of this technique has allowed access and drainage of the main
      pancreatic duct after failed endoscopic retrograde pancreatography and can avoid
      invasive procedures such as surgical and percutaneous interventions. This review
      discusses the indications, technique, challenges, and an algorithmic approach to
      EUS-guided pancreatic drainage. 

PMID- 25385530
TI  - Ionic selectivity and thermal adaptations within the voltage-gated sodium channel
      family of alkaliphilic Bacillus.
AB  - Entry and extrusion of cations are essential processes in living cells. In
      alkaliphilic prokaryotes, high external pH activates voltage-gated sodium
      channels (Nav), which allows Na(+) to enter and be used as substrate for
      cation/proton antiporters responsible for cytoplasmic pH homeostasis. Here, we
      describe a new member of the prokaryotic voltage-gated Na(+) channel family
      (NsvBa; <underline>N</underline>on-<underline>s</underline>elective
      <underline>v</underline>oltage-gated, <underline>B</underline>acillus
      <underline>a</underline>lcalophilus) that is nonselective among Na(+), Ca(2+) and
      K(+) ions. Mutations in NsvBa can convert the nonselective filter into one that
      discriminates for Na(+) or divalent cations. Gain-of-function experiments
      demonstrate the portability of ion selectivity with filter mutations to other
      Bacillus Nav channels. Increasing pH and temperature shifts their activation
      threshold towards their native resting membrane potential. Furthermore, we find
      drugs that target Bacillus Nav channels also block the growth of the bacteria.
      This work identifies some of the adaptations to achieve ion discrimination and
      gating in Bacillus Nav channels. 

PMID- 25385532
TI  - Predicting evolution from the shape of genealogical trees.
AB  - Given a sample of genome sequences from an asexual population, can one predict
      its evolutionary future? Here we demonstrate that the branching patterns of
      reconstructed genealogical trees contains information about the relative fitness
      of the sampled sequences and that this information can be used to predict
      successful strains. Our approach is based on the assumption that evolution
      proceeds by accumulation of small effect mutations, does not require species
      specific input and can be applied to any asexual population under persistent
      selection pressure. We demonstrate its performance using historical data on
      seasonal influenza A/H3N2 virus. We predict the progenitor lineage of the
      upcoming influenza season with near optimal performance in 30% of cases and make
      informative predictions in 16 out of 19 years. Beyond providing a tool for
      prediction, our ability to make informative predictions implies persistent
      fitness variation among circulating influenza A/H3N2 viruses. 

PMID- 25385531
TI  - Autophagy is a critical regulator of memory CD8(+) T cell formation.
AB  - During infection, CD8(+) T cells initially expand then contract, leaving a small
      memory pool providing long lasting immunity. While it has been described that
      CD8(+) T cell memory formation becomes defective in old age, the cellular
      mechanism is largely unknown. Autophagy is a major cellular lysosomal degradation
      pathway of bulk material, and levels are known to fall with age. In this study,
      we describe a novel role for autophagy in CD8(+) T cell memory formation. Mice
      lacking the autophagy gene Atg7 in T cells failed to establish CD8(+) T cell
      memory to influenza and MCMV infection. Interestingly, autophagy levels were
      diminished in CD8(+) T cells from aged mice. We could rejuvenate CD8(+) T cell
      responses in elderly mice in an autophagy dependent manner using the compound
      spermidine. This study reveals a cell intrinsic explanation for poor CD8(+) T
      cell memory in the elderly and potentially offers novel immune modulators to
      improve aged immunity. 

PMID- 25385533
TI  - Comparison of cortisol exposures and pharmacodynamic adrenal steroid responses to
      hydrocortisone suspension vs. commercial tablets.
AB  - The Endocrine Society Clinical Practice Guidelines on congenital adrenal
      hyperplasia (CAH) recommend against using hydrocortisone suspension based on a
      study that examined a commercial suspension. Our objective was to examine the
      absorption of an extemporaneously prepared hydrocortisone suspension and compare
      it to tablets. Secondary objectives were to evaluate the 17-hydroxyprogesterone
      and androstenedione adrenal steroid responses. Using a parallel design, 34
      children diagnosed with CAH received either suspension (n = 9; median age 1.8
      years) or tablets (n = 25; median age 7.5 years). Patients were given their usual
      morning hydrocortisone formulation and dose; 12 serial blood samples were
      obtained and the area under the curve (AUC) was calculated. The mg/m(2) dose
      normalized cortisol AUCs were no different in the suspension and tablet groups (P
      = .06), nor was there a significant difference in the C(max) or T(max) (P = .08
      and P = .41, respectively). Although there were no differences in the 17
      hydroxyprogesterone change-from-baseline AUCs, baseline concentrations, or the
      nadir concentrations when comparing suspension and tablet formulations, the
      androstenedione values were significantly lower as expected in the younger aged
      suspension group. Our results offer compelling evidence that an extemporaneously
      prepared hydrocortisone suspension provides comparable cortisol exposures to
      commercially available tablet formulations in children and can be used to safely
      and effectively treat CAH.

PMID- 25385534
TI  - Non-cultural methods for the diagnosis of invasive fungal disease.
AB  - Invasive fungal diseases carry a high mortality risk which can be reduced by
      early treatment. Diagnosing invasive fungal diseases is challenging, because
      invasive methods for obtaining histological samples are frequently not feasible
      in thrombocytopenic immunocompromised patients, while fungal cultures have low
      sensitivity and a long turn-around time. Non-cultural methods are fundamental for
      a rapid diagnosis of invasive fungal diseases and they include assays based on
      the detection of fungal antigens (galactomannan, Aspergillus-lateral flow device,
      [1,3]-beta-D-glucan, mannan), antibodies, such as anti-mannan, and molecular
      tests. With the exception of some molecular methods for rare fungi, the non
      cultural assays are usually applied to the diagnosis of invasive aspergillosis,
      invasive candidiasis and pneumocystosis. The performance of a single test or a
      combination of tests will be discussed, with particular focus on choosing the
      most appropriate marker(s) for every specific patient population. Reasons for
      potential false-positive or false-negative results will be discussed. 

PMID- 25385535
TI  - Layer-controlled CVD growth of large-area two-dimensional MoS2 films.
AB  - In spite of the recent heightened interest in molybdenum disulfide (MoS2) as a
      two-dimensional material with substantial bandgaps and reasonably high carrier
      mobility, a method for the layer-controlled and large-scale synthesis of high
      quality MoS2 films has not previously been established. Here, we demonstrate that
      layer-controlled and large-area CVD MoS2 films can be achieved by treating the
      surfaces of their bottom SiO2 substrates with the oxygen plasma process. Raman
      mapping, UV-Vis, and PL mapping are performed to show that mono, bi, and trilayer
      MoS2 films grown on the plasma treated substrates fully cover the centimeter
      scale substrates with a uniform thickness. Our TEM images also present the single
      crystalline nature of the monolayer MoS2 film and the formation of the layer
      controlled bi- and tri-layer MoS2 films. Back-gated transistors fabricated on
      these MoS2 films are found to exhibit the high current on/off ratio of ~10(6) and
      high mobility values of 3.6 cm(2) V(-1) s(-1) (monolayer), 8.2 cm(2) V(-1) s(-1)
      (bilayer), and 15.6 cm(2) V(-1) s(-1) (trilayer). Our results are expected to
      have a significant impact on further studies of the MoS2 growth mechanism as well
      as on the scaled layer-controlled production of high quality MoS2 films for a
      wide range of applications.

PMID- 25385538
TI  - Placebo cessation in binge eating disorder: effect on anthropometric,
      cardiovascular, and metabolic variables.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of cessation of
      binge eating in response to placebo treatment in binge eating disorder (BED) on
      anthropometric, cardiovascular, and metabolic variables. METHOD: We pooled
      participant-level data from 10 randomized, double-blind, placebo-controlled
      trials of medication for BED. We then compared patients who stopped binge eating
      with those who did not on changes in weight, body mass index (BMI), systolic and
      diastolic blood pressure, pulse, and fasting lipids and glucose. RESULT: Of 234
      participants receiving placebo, 60 (26%) attained cessation from binge eating.
      Patients attaining cessation showed modestly decreased diastolic blood pressure
      compared with patients who continued to binge eat. Weight and BMI remained stable
      in patients who stopped binge eating, but increased somewhat in those who
      continued to binge eat. DISCUSSION: Patients who stopped binge eating with
      placebo had greater reductions in diastolic blood pressure and gained less weight
      than patients who continued to binge eat. Self-report of eating pathology in BED
      may predict physiologic variables. Copyright (c) 2014 John Wiley & Sons, Ltd and
      Eating Disorders Association.

PMID- 25385537
TI  - Cardiovascular risks associated with incident and prevalent periodontal disease.
AB  - AIM: While prevalent periodontal disease associates with cardiovascular risk,
      little is known about how incident periodontal disease influences future vascular
      risk. We compared effects of incident versus prevalent periodontal disease in
      developing major cardiovascular diseases (CVD), myocardial infarction (MI),
      ischaemic stroke and total CVD. MATERIAL AND METHODS: In a prospective cohort of
      39,863 predominantly white women, age >=45 years and free of cardiovascular
      disease at baseline were followed for an average of 15.7 years. Cox proportional
      hazard models with time-varying periodontal status [prevalent (18%), incident
      (7.3%) versus never (74.7%)] were used to assess future cardiovascular risks.
      RESULTS: Incidence rates of all CVD outcomes were higher in women with prevalent
      or incident periodontal disease. For women with incident periodontal disease,
      risk factor adjusted hazard ratios (HRs) were 1.42 (95% CI, 1.14-1.77) for major
      CVD, 1.72 (1.25-2.38) for MI, 1.41 (1.02-1.95) for ischaemic stroke and 1.27
      (1.06-1.52) for total CVD. For women with prevalent periodontal disease, adjusted
      HRs were 1.14 (1.00-1.31) for major CVD, 1.27 (1.04-1.56) for MI, 1.12 (0.91
      1.37) for ischaemic stroke and 1.15 (1.03-1.28) for total CVD. CONCLUSION: New
      cases of periodontal disease, not just those that are pre-existing, place women
      at significantly elevated risks for future cardiovascular events.

PMID- 25385539
TI  - GP commissioners call for equal partnership on health and wellbeing boards.

PMID- 25385540
TI  - Variable density incoherent spatiotemporal acquisition (VISTA) for highly
      accelerated cardiac MRI.
AB  - PURPOSE: For the application of compressive sensing to parallel MRI, Poisson disk
      sampling (PDS) has been shown to generate superior results compared with random
      sampling methods. However, due to its limited flexibility to incorporate
      additional constraints, PDS is not readily extendible to dynamic applications.
      Here, we propose and validate a pseudo-random sampling technique that allows
      incorporating constraints specific to dynamic imaging. METHODS: The proposed
      sampling scheme, called variable density incoherent spatiotemporal acquisition
      (VISTA), is based on constrained minimization of Riesz energy on a spatiotemporal
      grid. Data from both a digital phantom and real-time cine were used to compare
      VISTA with uniform interleaved sampling (UIS) and variable density random
      sampling (VRS). The image quality was assessed qualitatively and quantitatively.
      RESULTS: VISTA improved the trade-off between noise and sharpness. Also, VISTA
      produced diagnostic quality images at an acceleration rate of 15, whereas UIS and
      VRS images degraded below the diagnostic threshold at lower acceleration rates.
      CONCLUSIONS: VISTA generates spatiotemporal sampling patterns with high levels of
      uniformity and incoherence, while maintaining a constant temporal resolution.
      Using a small pilot study, VISTA was shown to produce diagnostic quality images
      at acceleration rates up to 15.

PMID- 25385541
TI  - Environmental proxies of antigen exposure explain variation in immune investment
      better than indices of pace of life.
AB  - Investment in immune defences is predicted to covary with a variety of
      ecologically and evolutionarily relevant axes, with pace of life and
      environmental antigen exposure being two examples. These axes may themselves
      covary directly or inversely, and such relationships can lead to conflicting
      predictions regarding immune investment. If pace of life shapes immune investment
      then, following life history theory, slow-living, arid zone and tropical species
      should invest more in immunity than fast-living temperate species. Alternatively,
      if antigen exposure drives immune investment, then species in antigen-rich
      tropical and temperate environments are predicted to exhibit higher immune
      indices than species from antigen-poor arid locations. To test these contrasting
      predictions we investigated how variation in pace of life and antigen exposure
      influence immune investment in related lark species (Alaudidae) with differing
      life histories and predicted risks of exposure to environmental microbes and
      parasites. We used clutch size and total number of eggs laid per year as
      indicators of pace of life, and aridity, and the climatic variables that
      influence aridity, as correlates of antigen abundance. We quantified immune
      investment by measuring four indices of innate immunity. Pace of life explained
      little of the variation in immune investment, and only one immune measure
      correlated significantly with pace of life, but not in the predicted direction.
      Conversely, aridity, our proxy for environmental antigen exposure, was predictive
      of immune investment, and larks in more mesic environments had higher immune
      indices than those living in arid, low-risk locations. Our study suggests that
      abiotic environmental variables with strong ties to environmental antigen
      exposure can be important correlates of immunological variation. 

PMID- 25385543
TI  - Successful surgical treatment for total circumferential aortic and mitral annulus
      calcification: application of half-and-half technique.
AB  - Patients with total circumferential mitral annular calcification (MAC) extending
      into the intervalvular fibrous body and aortic annulus have a high risk of
      cardiac surgery, which remains a technical challenge for surgeons. Our technique
      for MAC is characterized as simple supra-mitral annular prosthesis insertion
      after minimum debridement of calcification ("half-and-half technique"). To date,
      our technique has been applied in only simple MAC cases and has good results.
      Herein, we report successful two cases of total circumferential MAC, extending
      into the intervalvular fibrous body and aortic annulus that were treated by a
      simple double valve replacement with application of our "half-and-half
      technique". 

PMID- 25385544
TI  - Crestal bone resorption in augmented bone using mineralized freeze-dried bone
      allograft or pristine bone during submerged implant healing: a prospective study
      in humans.
AB  - BACKGROUND: There is limited evidence on the crestal bone level changes around
      implants placed in bone augmented by guided bone regeneration (GBR) during
      submerged healing. The purpose of this study was to prospectively compare
      radiographic crestal bone changes around implants placed in augmented bone with
      changes around implants placed in pristine bone. MATERIALS AND METHODS: Patients
      receiving dental implants in the augmented or pristine mandibular posterior
      edentulous ridge were included in the study. The digital standardized radiographs
      from the implant placement procedure were compared to the radiographs from the
      second-stage procedure to evaluate the peri-implant marginal bone level changes.
      The soft tissue thickness (ST), width of keratinized mucosa (wKM), and early
      cover screw exposure (eIE) were measured at the time of the second-stage
      procedure. RESULTS: A total of 29 implants in 26 patients, 11 in augmented bone
      (test group) and 18 in pristine bone (control group), were analyzed. The mean
      peri-implant bone loss (DeltaBL) was 0.74 +/- 0.74 mm (mean +/- SD) in the test
      group and 0.25 +/- 0.55 mm (mean +/- SD) in the control group. The differences
      between the test and control groups in the mesial, distal, and mean peri-implant
      crestal bone level changes were statistically significant (P = 0.009, P = 0.004,
      and P = 0.001, respectively). The confounding factors (ST, wKM, and eIE) were
      adjusted. CONCLUSIONS: More peri-implant crestal bone loss during the submerged
      healing period was observed in augmented bone than in pristine bone. Augmented
      bone may not exhibit the same characteristics as pristine bone during the implant
      submerged healing period.

PMID- 25385545
TI  - Relative ordering between bright and dark excitons in single-walled carbon
      nanotubes.
AB  - The ordering and relative energy splitting between bright and dark excitons are
      critical to the optical properties of single-walled carbon nanotubes (SWNTs), as
      they eventually determine the radiative and non-radiative recombination processes
      of generated carriers. In this work, we report systematic high-field magneto
      optical study on the relative ordering between bright and dark excitons in SWNTs.
      We identified the relative energy position of the dark exciton unambiguously by
      brightening it in ultra-high magnetic field. The bright-dark excitonic ordering
      was found to depend not only on the tube structure, but also on the type of
      transitions. For the 1(st) sub-band transition, the bright exciton appears to be
      higher in energy than its dark counterpart for any chiral species and is robust
      against environmental effect. While for the 2(nd) sub-band, their relative
      ordering was found to be chirality-sensitive: the bright exciton can be either
      higher or lower than the dark one, depending on the specific nanotube structures.
      These findings provide new clues for engineering the optical and electronic
      properties of SWNTs. 

PMID- 25385547
TI  - Lone pair-pi interaction-induced generation of non-interpenetrated and
      photochromic cuboid 3-D naphthalene diimide coordination networks.
AB  - Interpenetration is an intrinsic behaviour for the porous coordination networks.
      To prevent the interpenetration, a common strategy is the imposition of geometric
      or steric restrictions by incorporating bulky moieties into organic tectons. So
      far, most of the available incorporations have been achieved through a covalent
      connection, while few involved in the non-covalent weak interactions. In this
      paper, we have reported that such interpenetration can be prevented by the less
      common lone pair-pi interactions. By imposing the lone pair-pi interactions
      through the addition of lone-pair-bearing N-methylpyrrolidin-2-one or iodine,
      combinations of rigid naphthalene diimide tectons bearing two divergently
      oriented pyridyl units at both imide extremities with ZnSiF6 led to non
      interpenetrated cuboid 3-D coordination networks that should have been
      interpenetrated. In addition, such close-contacting lone pair-pi interactions
      between electron donors and acceptors have also been demonstrated to play a key
      role in their photochromic properties. 

PMID- 25385548
TI  - Aerobic capacity of Peruvian Quechua: a test of the developmental adaptation
      hypothesis.
AB  - High altitude natives are reported to have outstanding work capacity in spite of
      the challenge of oxygen transport and delivery in hypoxia. To evaluate the
      developmental effect of lifelong exposure to hypoxia on aerobic capacity, VO2peak
      was measured on two groups of Peruvian Quechua subjects (18-35 years), who
      differed in their developmental exposure to altitude. Male and female volunteers
      were recruited in Lima, Peru (150 m), and were divided in two groups, based on
      their developmental exposure to hypoxia, those: a) Born at sea-level individuals
      (BSL), with no developmental exposure to hypoxia (n = 34) and b) Born at high
      altitude individuals (BHA) with full developmental exposure to hypoxia (n = 32),
      but who migrated to sea-level as adults (>16-years-old). Tests were conducted
      both in normoxia (BP = 750 mm Hg) and normobaric hypoxia at sea-level (BP = 750
      mm Hg, FiO2  = 0.12, equivalent to 4,449 m), after a 2-month training period (in
      order to control for initial differences in physical fitness) at sea-level. BHA
      had a significantly higher VO2peak at hypoxia (40.31 +/- 1.0 ml/min/kg) as
      compared to BSL (35.78 +/- 0.96 ml/min/kg, P = 0.001), adjusting for sex. The
      decrease of VO2peak at HA relative to SL (DeltaVO2peak ) was not different
      between groups, controlling for baseline levels (VO2peak at sea-level) and sex
      (BHA = 0.35 +/- 0.04 l/min, BSL = 0.44 +/- 0.04 l/min; P = 0.12). Forced vital
      capacity (controlling for height) and the residuals of VO2peak (controlling for
      weight) had a significant association in the BHA group only (r = 0.155; P =
      0.031). In sum, results indicate that developmental exposure to altitude
      constitutes an important factor to determine superior exercise performance.

PMID- 25385546
TI  - Structural basis for extracellular cis and trans RPTPsigma signal competition in
      synaptogenesis.
AB  - Receptor protein tyrosine phosphatase sigma (RPTPsigma) regulates neuronal
      extension and acts as a presynaptic nexus for multiple protein and proteoglycan
      interactions during synaptogenesis. Unknown mechanisms govern the shift in
      RPTPsigma function, from outgrowth promotion to synaptic organization. Here, we
      report crystallographic, electron microscopic and small-angle X-ray scattering
      analyses, which reveal sufficient inter-domain flexibility in the RPTPsigma
      extracellular region for interaction with both cis (same cell) and trans
      (opposite cell) ligands. Crystal structures of RPTPsigma bound to its
      postsynaptic ligand TrkC detail an interaction surface partially overlapping the
      glycosaminoglycan-binding site. Accordingly, heparan sulphate and heparin
      oligomers compete with TrkC for RPTPsigma binding in vitro and disrupt TrkC
      dependent synaptic differentiation in neuronal co-culture assays. We propose that
      transient RPTPsigma ectodomain emergence from the presynaptic proteoglycan layer
      allows capture by TrkC to form a trans-synaptic complex, the consequent reduction
      in RPTPsigma flexibility potentiating interactions with additional ligands to
      orchestrate excitatory synapse formation. 

PMID- 25385549
TI  - Transfusion-associated Anaplasma phagocytophilum infection in a pregnant patient
      with thalassemia trait: a case report.
AB  - BACKGROUND: Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile
      illness caused by the bacterium Anaplasma phagocytophilum. Although usually
      transmitted via tick bite, HGA may rarely also be acquired through transfusion.
      HGA during pregnancy may pose significant gestational risks due to altered
      maternal immune status and the potential for perinatal transmission. CASE REPORT:
      A pregnant 34-year-old Massachusetts woman with beta-thalassemia trait was
      diagnosed at 32 weeks of gestation with transfusion-associated HGA (TAHGA) after
      receiving nine leukoreduced red blood cell transfusions. She was successfully
      treated with rifampin therapy and gave birth to a healthy child who tested
      negative for HGA after delivery. An implicated blood donor was subsequently
      identified through physician collaboration with the regional American Red Cross
      and Massachusetts Department of Public Health. DISCUSSION: This is the 11th
      reported case of HGA in pregnancy and is at least the sixth known case in which
      leukoreduction did not prevent TAHGA. As seen in this case, nonspecific
      symptomatology of variable onset can impede diagnosis and treatment. This may
      increase risk of poor outcomes in maternal HGA patients. Cases of TAHGA, although
      currently uncommon, may increase as the incidence of HGA in certain parts of the
      country increases. CONCLUSION: Heightened cross-institutional awareness of the
      potential risk of TAHGA is warranted. Clinicians need to consider transfusion
      associated infections when fever occurs in a transfusion recipient. This case
      provides additional evidence that leukoreduction does not obviate risk of A.
      phagocytophilum contamination of donated blood components.

PMID- 25385551
TI  - Is 40 the new 30?

PMID- 25385550
TI  - Function of the Th17/interleukin-17A immune response in murine lupus nephritis.
AB  - OBJECTIVE: The CD4+ T cell immune response plays a pivotal role in the
      immunopathogenesis of human and experimental lupus nephritis, but the
      contribution of the Th17/interleukin-17 (IL-17) immune pathway to renal tissue
      injury in systemic lupus erythematosus (SLE) remains to be elucidated. The aim of
      this study was to characterize the function of the Th17/IL-17A immune response in
      2 murine models of lupus nephritis. METHODS: IL-17A-deficient MRL/MPJ-Fas(lpr)
      /2J (MRL/lpr) mice were generated, and the clinical course of nephritis was
      monitored by assessing the levels of albuminuria, extent of renal tissue injury,
      and functional parameters. In addition, lupus-prone (NZB * NZW)F1 (NZB/NZW) mice
      were treated with anti-IL-17A and anti-interferon-gamma (anti-IFNgamma)
      antibodies, and their effects on the clinical course of lupus nephritis were
      assessed. RESULTS: Characterization of renal IL-17A-producing and IFNgamma
      producing T cells in MRL/lpr and NZB/NZW mice revealed low numbers of
      infiltrating CD3+IL-17A+ cells. Renal IL-17A was mainly produced by CD4/CD8
      double-negative CD3+ T cells and CD4+ Th17 cells. In contrast, the number of
      renal CD3+IFNgamma+ cells continuously increased over time and largely consisted
      of typical CD4+ Th1 cells. IL-17A deficiency did not affect the morphologic or
      functional parameters in MRL/lpr mice with lupus nephritis, nor did IL-17A
      neutralization affect the clinical course of nephritis in NZB/NZW mice, but anti
      IFNgamma treatment attenuated the severity of the disease. CONCLUSION: The
      Th17/IL-17A immune response plays no major role in the immunopathogenesis of
      lupus nephritis in MRL/lpr and NZB/NZW mice. Thus, the results of this study do
      not support the hypothesis that IL-17A targeting could be an intriguing new
      therapeutic approach for the management of proliferative lupus nephritis in SLE
      patients.

PMID- 25385552
TI  - Effects of 5-fluorouracil and class III phosphoinositide 3-kinase small
      interfering RNA combination therapy on SGC7901 human gastric cancer cells.
AB  - The aim of the present study was to investigate the effects of small interfering
      RNA-mediated inhibition of Class III phosphoinositide 3-kinase (PI3K) signal
      transduction on the proliferation, apoptosis and autophagy of SGC7901 gastric
      cancer cells. The present study also aimed to examine the contribution of
      autophagic inhibition to the antitumor effects of 5-fluorouracil (5-FU). A
      PI3K(III)-RNA interference (i)-green fluorescent protein (GFP) recombinant
      replication adenovirus (AD) and the negative control (NC)-RNAi-GFP control AD
      were constructed and infected into SGC7901 cells. A methyl thiazolyl tetrazolium
      assay was used to determine the growth rate of the SGC7901 cells.
      Immunofluorescent staining was used to detect microtubule-associated protein 1
      light chain 3 expression. The mitochondrial membrane potential was measured using
      the JC-1 fluorescent probe. Autophagic expression was monitored with MDC staining
      and transmission electron microscopy. The results revealed that following
      combination treatment of the SGC7901 gastric cancer cells with 5-FU + PI3K(III)
      RNAi-AD, the optical density absorbance values at 24, 48 and 72 h were 0.17 +/-
      1.64, 0.13 +/- 4.64 and 0.11 +/- 3.56%, respectively, with cell viability
      inhibition ratios of 45.89 +/- 6.67, 72.57 +/- 9.48 and 87.51 +/- 4.65%,
      respectively. As compared with the other treatment groups, the inhibition rate in
      the combined treatment group was significantly higher (P<0.05). The percentages
      of the cells with green fluorescence in the combined treatment group were 74.4 +/
      3.86 (24 h), 82.3 +/- 1.84 (48 h) and 92.5 +/- 1.1% (72 h), which were larger
      than those of the other groups. The percentage of cells with green fluorescence
      became larger, which indicated that the mitochondrion membrane potential had been
      reduced to a greater extent. MDC staining revealed that the number of autophagic
      vacuoles in the cells (measured at 24, 48 and 72 h) decreased gradually with
      time, with more autophagic vacuoles observed in the cells in the control group at
      24 h than those in the other treatment groups. Fewest autophagic vacuoles were
      identified in the combined treatment group. Using a fluorescence microscope, the
      immune fluorescence expression of microtubule-associated proteins 1A/1B light
      chain 3A, which is the specific protein of autophagy, in the combined treatment
      group was observed to be significantly downregulated, as compared with the other
      groups. As determined by transmission electron microscopic observation of the
      SGC7901 gastric cancer cells, the degree of autophagy in the combined treatment
      group was significantly reduced, as compared with that of the other treatment
      groups. In conclusion, following combined treatment with 5-FU and an inhibitor of
      class III PI3K signal transduction, the proliferation of SGC7901 cells was
      significantly suppressed, the mitochondrion membrane potentials were
      significantly reduced and the expression levels of autophagic markers were
      significantly downregulated.

PMID- 25385554
TI  - Autoimmunity and tumor immunology: two facets of a probabilistic immune system.
AB  - BACKGROUND: The immune system of vertebrates has evolved the ability to mount
      highly elaborate responses to a broad range of pathogen-driven threats.
      Accordingly, it is quite a challenge to understand how a primitive adaptive
      immune system that probably lacked much of its present complexity could provide
      its bearers with significant evolutionary advantage, and therefore, continue to
      be selected for. RESULTS: We have developed a very simple model of the immune
      system that captures the probabilistic communication between its innate and
      adaptive components. Probabilistic communication arises specifically from the
      fact that antigen presenting cells collect and present a range of antigens from
      which the adaptive immune system must (probabilistically) identify its target.
      Our results show that although some degree of self-reactivity in the immune
      repertoire is unavoidable, the system is generally able to correctly target
      pathogens rather than self-antigens. Particular circumstances that impair correct
      targeting and that may lead to infection-induced autoimmunity can be predicted
      within this framework. Notably, the probabilistic immune system exhibits the
      remarkable ability to detect sudden increases in the abundance of rare self
      antigens, which represents a first step towards developing anti-tumoral
      responses. CONCLUSION: A simple probabilistic model of the communication between
      the innate and adaptive immune system provides a robust immune response,
      including targeting tumors, but at the price of being at risk of developing
      autoimmunity.

PMID- 25385555
TI  - Comparing glycemic indicators of prediabetes: a prospective study of obese Latino
      Youth.
AB  - OBJECTIVE: One hour (1-hr) glucose during an oral glucose tolerance test (OGTT)
      is an emerging biomarker for type 2 diabetes. We compared the predictive power of
      1-hr glucose to traditional glycemic markers for prospectively identifying
      prediabetes in youth. RESEARCH DESIGN AND METHODS: Obese normoglycemic Latino
      youth (N = 116) were assessed at baseline for glycated hemoglobin (HbA1c),
      fasting, 1-hr, and 2-hr glucose during an OGTT and were followed for up to 8 yr
      for the development of prediabetes. Receiver operating characteristic (ROC)
      curves were used and a multivariable prediction model was developed. RESULTS: The
      area under the 1-hr glucose ROC curve was the most powerful predictor of
      prediabetes over time [0.73, 95% confidence interval (CI) = 0.64-0.83]. However,
      combining all indicators into a single model was superior to individual marker
      models (0.77, 95% CI = 0.690.86). CONCLUSIONS: These results further support the
      utility of 1-hr glucose during an OGTT as a prospective marker of diabetes risk
      in youth.

PMID- 25385557
TI  - Cohesion, team mental models, and collective efficacy: towards an integrated
      framework of team dynamics in sport.
AB  - A nomological network on team dynamics in sports consisting of a multiframework
      perspective is introduced and tested. The aim was to explore the
      interrelationship among cohesion, team mental models (TMMs), collective efficacy
      (CE) and perceived performance potential (PPP). Three hundred and forty college
      aged soccer players representing 17 different teams (8 female and 9 male)
      participated in the study. They responded to surveys on team cohesion, TMMs, CE
      and PPP. Results are congruent with the theoretical conceptualisation of a
      parsimonious view of team dynamics in sports. Specifically, cohesion was found to
      be an exogenous variable predicting both TMMs and CE beliefs. TMMs and CE were
      correlated and predicted PPP, which in turn accounted for 59% of the variance of
      objective performance scores as measured by teams' season record. From a
      theoretical standpoint, findings resulted in a parsimonious view of team
      dynamics, which may represent an initial step towards clarifying the
      epistemological roots and nomological network of various team-level properties.
      From an applied standpoint, results suggest that team expertise starts with the
      establishment of team cohesion. Following the establishment of cohesiveness,
      teammates are able to advance team-related schemas and a collective sense of
      confidence. Limitations and key directions for future research are outlined.

PMID- 25385556
TI  - Pramipexole extended-release: a review of its use in patients with Parkinson's
      disease.
AB  - Pramipexole, a non-ergolinic, D3-preferring dopamine agonist (DA), is well
      established as a treatment option for motor symptoms at all stages of Parkinson's
      disease (PD). It is administered orally and is available as both a three-times
      daily immediate-release (IR) formulation and a once-daily extended-release (ER)
      formulation (Mirapex((r)) ER, Mirapexin((r)) ER; Pexola((r)) ER, Sifrol((r)) ER).
      The two formulations are bioequivalent; the majority (>80 %) of patients can be
      switched overnight from pramipexole IR to ER without the need for dosage
      adjustment. In terms of improving activities of daily living and motor function
      in short-term (<=33-week), double-blind studies, pramipexole ER was noninferior
      to pramipexole IR and significantly more effective than placebo as monotherapy in
      patients with early PD, and similar to pramipexole IR and significantly more
      effective than placebo as adjunctive therapy to levodopa in patients with
      advanced PD. In long-term (80-week) extensions of these trials, open-label
      treatment with pramipexole ER was associated with sustained symptomatic benefit.
      Moreover, the majority of extension participants who responded to a simple
      convenience questionnaire expressed a preference for once-daily over three-times
      daily dosing. Pramipexole ER was generally well tolerated in clinical trials; no
      new or unexpected safety signals were identified compared with the IR
      formulation. Head-to-head trials are needed in order to fully define the role of
      pramipexole ER relative to other once-daily formulations of DAs (oral ropinirole
      and transdermal rotigotine). Nonetheless, by reducing the pill burden, the ER
      formulation of pramipexole provides a more convenient alternative to the IR
      formulation; studies specifically testing whether this translates into improved
      patient compliance and symptom control are worthwhile.

PMID- 25385558
TI  - Pyoderma gangrenosum as a first presentation of inflammatory bowel disease.
AB  - Up to 40% of patients with inflammatory bowel disease (IBD) develop an
      extraintestinal manifestation of the disease with the skin being the most
      commonly involved organ. Pyoderma gangrenosum (PG), an autoinflammatory non
      infectious neutrophilic dermatosis, occurs in 1-2% of patients with IBD. PG can
      follow a course independent to that of the bowel disease, however, most reported
      cases describe PG occurring in patients with an established diagnosis of IBD. We
      present a case of a young patient who presented with axillary skin ulceration,
      which was subsequently diagnosed as PG. On further investigation for a possible
      underlying cause, she was found to have Crohn's disease. She had not developed
      any preceding change in her bowels and did not have abdominal pain; the IBD was
      diagnosed on endoscopic findings. This case is also unusual for the distribution
      of the PG lesions that typically occur in the lower limbs. 

PMID- 25385559
TI  - Tuberculous lymphadenitis and borderline leprosy in a patient with isolated
      unconjugated hyperbilirubinaemia.
AB  - A 35-year-old man was diagnosed with tuberculous lymphadenitis and multibacillary
      borderline tuberculoid leprosy. On investigation, isolated unconjugated
      hyperbilirubinaemia was detected and evaluation led us to conclude that the
      probable cause was Gilbert's syndrome. He was successfully managed by
      administration of chemotherapy for the treatment of both the mycobacterial
      infections, with no adverse effects on liver function tests. 

PMID- 25385560
TI  - Treatment of recalcitrant subcutaneous emphysema using negative pressure wound
      therapy dressings.
AB  - Subcutaneous emphysema frequently occurs after pulmonary resection, but is
      usually mild and self-limiting. Patients can, however, develop severe symptomatic
      subcutaneous emphysema despite adequate thoracic drainage. There is a paucity of
      efficacious treatments for subcutaneous emphysema that does not respond to chest
      tube drainage. Previous reports have suggested that thoracoscopy may be an
      efficacious treatment, but is unfavourable due to the risks associated with
      reoperation. We present a case of a patient who developed severe subcutaneous
      emphysema after pulmonary lobectomy that was quickly and effectively treated
      using a commercially available negative pressure wound therapy dressing. 

PMID- 25385561
TI  - Sturge-Weber syndrome: CT and MRI illustrations.

PMID- 25385562
TI  - A report of a successfully treated case of ABPA in an HIV-infected individual.
AB  - Aspergillus fumigatus is a ubiquitous fungus responsible for a variety of
      pulmonary diseases, ranging from infection of a pre-existing cavity as in
      aspergilloma to highly invasive disease in immunocompromised hosts. Allergic
      bronchopulmonary aspergillosis (ABPA) is a hypersensitivity response mounted
      against antigens of A. fumigatus manifesting as poorly controlled asthma and
      bronchiectasis. Although ABPA is not uncommon, occurrence of ABPA in HIV-affected
      individuals is distinctly rare. We describe the occurrence of ABPA in a 35-year
      old woman with poorly controlled asthma since childhood and HIV-1 infection of 11
      years duration. This is the second documented case of ABPA in a HIV-affected
      individual, and the first reported case to be successfully managed with
      antifungal therapy alone. We also discuss the complex management issues involved
      in treating ABPA in HIV-affected individuals.

PMID- 25385563
TI  - 'How to deal with this, that and the other?' An orthopaedic surgeon's unexpected
      encounter with a trio of problems in an elderly man.
AB  - This is the first clinical report of a psoas abscess encountered during a routine
      hemiarthroplasty surgery for a femoral neck fracture in a man with a recent
      urinary tract infection. There were no prior symptoms to suggest a psoas abscess,
      which was present on the same side as the hip fracture, apart from a history of
      recurrent urinary tract infection. The surgery had to be altered intraoperatively
      to that of an excision arthroplasty of the displaced non-viable femoral head
      along with insertion of an antibiotic-impregnated cement spacer into the hip
      joint. Relevant microbiological studies confirmed a methicillin-sensitive
      Staphylococcus aureus psoas abscess with bacteraemia in addition to
      Staphylococcus bacteriuria, so 6 weeks of intravenous antibiotics were started. A
      planned second-stage hemiarthroplasty was undertaken and the patient recovered
      fully without complications. Primary infection of the urinary tract by S. aureus
      is rare. This case serves to remind clinicians that caution must be exercised in
      patients with recurrent infections, especially when such infections affect organs
      or areas close to the intended surgery site. This warrants thorough evaluation
      for an occult source of infection. A psoas abscess is an unusual cause of hip
      pain and accurate diagnosis relies on a high index of suspicion. The antibiotic
      impregnated articulating cement spacer is a useful surgical adjunct after
      excision arthroplasty, it not only elutes a high concentration of antibiotics in
      the infected field, but also facilitates second-stage arthroplasty surgery by
      preventing muscle and soft tissue contractures from developing.

PMID- 25385564
TI  - Ludwig's angina: need for including airways and larynx in ultrasound evaluation.
AB  - Ludwig's angina is a deep neck space infection. Unlike other abscesses elsewhere
      in the body, rapid progression of the disease results in serious complications
      such as airway oedema, distortion, total obstruction with loss of airway and
      death. Thus, early diagnosis and skilful airway management is necessary. For safe
      airway management, fibreoptic intubation or tracheostomy under local anaesthesia
      is recommended.1 We describe a case report where an initial attempt at fibreoptic
      intubation failed and subsequently bleeding ensued causing difficulty in viewing
      the larynx by fibreoptic bronchoscopy. Radiological investigations such as
      ultrasound and computer tomography (CT) are commonly ordered by surgeons and
      emergency physicians to know the extension of disease, but airways and larynx are
      seldom included. We discuss the role of ultrasound in airway assessment in such
      critical cases to ensure safe and uncomplicated airway access.

PMID- 25385565
TI  - Pain relief in a young woman with adhesive capsulitis after manual manipulation
      of the acromioclavicular joint for remaining symptoms after mobilisation under
      anaesthesia.
AB  - Adhesive capsulitis is a painful condition with a prevalence of 2-5%. There is a
      lack of evidence for its aetiology and for conventional treatment and cost
      effects. This study describes the treatment effects of manual manipulation of the
      acromioclavicular joint for adhesive capsulitis in a young woman for persisting
      pain after mobilisation of the glenohumeral joint under anaesthesia. Primary
      outcomes were pain and physical function, measured by a visual analogue scale and
      the SF36 health survey. Secondary outcomes were sleep pattern, medication and
      perceived recovery. The mobility after manipulation under anaesthesia: elevation
      55 degrees  and no improvement in pain. After manual manipulation: unrestricted
      elevation and significant pain relief. The patient no longer suffered from
      sleeping disorders and ceased all medication. Considering the lack of knowledge
      in aetiology and treatment, specialised manual examination of the
      acromioclavicular joint should be considered early in patients diagnosed with
      adhesive capsulitis. 

PMID- 25385566
TI  - Syringomyelia and Arnold-Chiari malformation associated with neck pain and left
      arm radiculopathy treated with spinal manipulation.
AB  - An 18-year-old female patient presented with left dominant neck pain after a
      motor vehicle collision. Her cervical spine MRI revealed syringomyelia with
      associated Type I Arnold-Chiari malformation. Some researchers have reported that
      these might be considered contraindications to spinal manipulation. Nevertheless,
      her benign and functional clinical examination suggested otherwise and she
      underwent four manipulative treatments in 2 weeks. By the end of the treatment
      plan and after 1-month follow-up, she was asymptomatic, no adverse effects were
      noted and her outcome assessment score decreased from 56% to 0%. This case
      illustrates that spinal manipulation may be a useful adjunctive treatment
      procedure for spinal pain, even in the presence of syringomyelia and Chiari
      malformation, which may not necessarily be a contraindication to spinal
      manipulation, when performed by a skilled and well-trained physician.

PMID- 25385567
TI  - Purple urinary bag syndrome.

PMID- 25385568
TI  - A giant complex rectosigmoid bezoar with multiple foreign bodies: a first of its
      kind.

PMID- 25385569
TI  - Mutations in GJB6 causing phenotype resembling pachyonychia congenita.

PMID- 25385570
TI  - Lanthanum lead oxide hydroxide nitrates with a nonlinear optical effect.
AB  - Two new lanthanum lead oxide hydroxide nitrates with acentric structure,
      [LaPb8O(OH)10(H2O)](NO3)7 (1) and [LaPb8O(OH)10(H2O)](NO3)7.2H2O (2), have been
      prepared under subcritical hydrothermal conditions and crystallize in the space
      groups of Cc and P2(1)2(1)2(1), respectively. The crystal structure of compound 1
      consists of the novel [LaPb8O(OH)10(H2O)](7+) clusters regularly arranged along
      the ab plane with nitrate ions as the counterions around the clusters by Pb-O
      bonds, developing into a three-dimensional net framework, while the structure of
      compound 2 is composed of [LaPb8O(OH)10(H2O)](7+) clusters and [NO3](-) groups as
      the bridging groups, forming a three-dimensional net framework with crystallized
      water molecules filling in the gaps. The experiments confirmed that compound 1 is
      the residue of compound 2 after efflorenscence. Besides, the
      [LaPb8O(OH)10(H2O)](7+) clusters present mirror symmetry in structures of the two
      compounds. The second-harmonic-generation (SHG) measurements for the two nitrates
      indicate that the SHG responses for compounds 1 and 2 are 1.3 and 1.1 times that
      of KH2PO4, respectively. Theoretical calculations confirmed that the SHG
      efficiency of compounds 1 and 2 mainly arises from the NO3(-) groups in the
      structure.

PMID- 25385571
TI  - A pilot study of conically graded chitosan-gelatin hydrogel/PLGA scaffold with
      dual-delivery of TGF-beta1 and BMP-2 for regeneration of cartilage-bone
      interface.
AB  - Repair of cartilage-bone interface tissue remains challenging, because it
      combines different cell types and gradients of composition and properties. To
      enable simultaneous regeneration of bone, cartilage, and especially their
      interface, a conically graded scaffold of chitosan-gelatin hydrogel/poly(l
      lactide-co-glycolide) (PLGA) was facilely prepared in the study. The chitosan
      gelatin hydrogel containing transforming growth factor beta1 (TGF-beta1) was used
      for chondrogenesis, while the PLGA scaffold loading bone morphogenetic protein-2
      (BMP-2) for osteogenesis. The conically graded transition from the hydrogel to
      PLGA scaffold and graded variation in amount of growth factors from TGF-beta1 to
      BMP-2 benefited the cartilage-bone interface reconstruction. The graded scaffold
      exhibited spatio-temporal delivery of TGF-beta1 and BMP-2. Preliminary results of
      in vitro cell culture demonstrated that the hydrogel and PLGA phases could
      promote bone marrow mesenchymal stem cells toward chondrogenic and osteogenic
      differentiation, respectively. From the result of the pilot in vivo experiment,
      it showed that the regenerated hyaline-like cartilage surface and subchondral
      bone excellently integrated with the native tissues were found by using the TGF
      beta1 and BMP-2 double-loaded hydrogel/PLGA graded scaffold via H&E and
      immunohistochemical stainings of collagen I, collagen II, and osteocalcin at 2
      months. The obtained preliminary experiment results showed that the hydrogel/PLGA
      graded scaffold combining multiphasic composition and spatial dual growth-factor
      delivery would be useful for cartilage-bone interface tissue defect repair.

PMID- 25385572
TI  - MTSS1 suppresses cell migration and invasion by targeting CTTN in glioblastoma.
AB  - Glioblastomas (GBMs) are the highest grade of primary brain tumors with
      astrocytic similarity and are characterized dispersal of tumor cell. Metastasis
      suppressor 1 (MTSS1) play an important role in cancer metastasis. Recent studies
      indicating that MTSS1 as a potential tumor suppressor and its reduced expression
      associated with poor prognosis in many cancer types. However, the relationship
      with the prognosis of patients and the molecular mechanism of MTSS1 renders a
      tumor suppressor effect in GBM is unknown. Here, we showed that low MTSS1 gene
      expression is associated with poor outcomes in patients with GBM. Overexpression
      of MTSS1 in U-87 MG cells exhibited inhibited glioma cell growth, colony
      formation, migration and invasion. Mechanistically, we found that high MTSS1
      expression in U-87 MG reduced expression of CTTN. These results implicate that
      the role of MTSS1 suppresses cell migration and invasion by inhibiting expression
      of CTTN and as a prognosis biomarker in GBM. 

PMID- 25385573
TI  - A comparative study of intraventricular central neurocytomas and extraventricular
      neurocytomas.
AB  - Similar histology and clinical behavior of both intraventricular central
      neurocytomas (CNs) and extraventricular neurocytomas (EVNs) may argue against the
      idea that EVNs were the distinct entity to distinguish from CNs in the 2007 World
      Health Organization classification. To explore respective characteristics and
      compare similarities and differences in CNs and EVNs, relevant clinical,
      radiological, operative and pathological data of 49 patients (35 CNs and 14 EVNs)
      in the Department of Neurosurgery at our hospital from 2005 to 2012 was reviewed
      and some comparisons between CNs and EVNs were conducted. The factors affecting
      posttreatment recurrence of CNs and EVNs were assessed by Cox regression
      analysis. In comparison, CNs showed a more typical clinical manifestation, and
      radiological and histopathological features, while EVNs demonstrated more
      malignant biological behavior, with higher MIB-1 index (p = 0.006), higher rate
      of atypia (p = 0.042), higher recurrence rate (p = 0.028), and shorter time to
      recurrence (p = 0.049). Subtotal resection was associated with higher rates of
      recurrence in both CNs (hazard ratio [HR] 6.16, p = 0.046) and EVNs (HR 5.26, p =
      0.045), and atypia was also associated with a higher recurrence rate in CNs (HR
      5.03, p = 0.042). CNs were thus easier to diagnose than EVNs, with typical
      clinical, radiological, and histopathological features, while the latter were
      more likely to show malignant biological behavior associated with atypia and
      recurrence. Total surgical resection is the optimal treatment choice for both CNs
      and EVNs, and patients with either CN or EVN with typical and/or totally resected
      lesions showed favorable clinical outcomes.

PMID- 25385574
TI  - Irrespective of size, scales, color or body shape, all fish are just fish: object
      categorization in the gray bamboo shark Chiloscyllium griseum.
AB  - Object categorization is an important cognitive adaptation, quickly providing an
      animal with relevant and potentially life-saving information. It can be defined
      as the process whereby objects that are not the same, are nonetheless grouped
      together according to some defining feature(s) and responded to as if they were
      the same. In this way, knowledge about one object, behavior or situation can be
      extrapolated onto another without much cost and effort. Many vertebrates
      including humans, monkeys, birds and teleosts have been shown to be able to
      categorize, with abilities varying between species and tasks. This study assessed
      object categorization skills in the gray bamboo shark Chiloscyllium griseum.
      Sharks learned to distinguish between the two categories, 'fish' versus 'snail'
      independently of image features and image type, i.e., black and white drawings,
      photographs, comics or negative images. Transfer tests indicated that sharks
      predominantly focused on and categorized the positive stimulus, while
      disregarding the negative stimulus. 

PMID- 25385576
TI  - Mass shootings: a meta-analysis of the dose-response relationship.
AB  - A meta-analysis was conducted to examine the dose-response theory as it relates
      to posttraumatic stress symptoms (PTSSs) following mass shootings. It was
      hypothesized that greater exposure to a mass shooting would be associated with
      greater PTSSs. Trauma exposure in the current study was broadly defined as the
      extent to which a person experienced or learned about a mass shooting. The meta
      analysis identified 11 qualifying studies that included 13 independent effect
      sizes from a total of 8,047 participants. The overall weighted mean effect size,
      based on a random effects model, was r = .19, p < .001, 95% CI [.13, .25].
      Maximum likelihood meta-regressions revealed no significant linear effects of
      participant gender, participant age, or time elapsed since the shooting on the
      relationship between exposure and PTSSs. Because so few studies satisfied the
      inclusion criteria, the present study also documents that this area of the
      literature is underresearched. 

PMID- 25385577
TI  - A rare case of narrow QRS complex tachycardia.

PMID- 25385575
TI  - Emotions on the loose: emotional contagion and the role of oxytocin in pigs.
AB  - We studied emotional contagion, a simple form of empathy, and the role of
      oxytocin herein in pigs. Two training pigs per pen (n = 16 pens) were subjected
      to a positive treatment (pairwise access to a large compartment filled with peat,
      straw and some chocolate raisins) and a negative treatment (social isolation in a
      small compartment) in a test room using a within-subjects design. Thereafter, two
      naive pen mates joined the training pigs in the test room, but were not given
      access to the treatments. This allowed testing for emotional contagion.
      Subsequently, the naive pigs, serving as their own controls, were given 24 IU of
      oxytocin or a placebo intranasally 30 min before accompanying the training pigs,
      which were exposed to either the negative or positive treatment, to the test
      room. Behavioral differences found between the positive and negative treatments
      (e.g., play and "tail wagging" vs. standing alert, urinating, defecating and ears
      backward) show that the treatments induced a positive and negative emotional
      state in the training pigs, respectively. Changes in behaviors of the training
      pigs with and without naive pigs present (e.g., in ears backwards) and of the
      naive pigs with and without training pigs present (e.g., in standing alert)
      indicated that emotional contagion occurred, especially during the negative
      treatment. Oxytocin did not seem to affect the behavior of the treated naive
      pigs, but did affect behaviors (e.g., defecating) of the training pigs which had
      not received oxytocin. This suggests a role for oxytocin in pig communication,
      which merits further research. 

PMID- 25385578
TI  - Chemistry: interdisciplinary and international-and with a sense of history.

PMID- 25385579
TI  - H19 long noncoding RNA controls the mRNA decay promoting function of KSRP.
AB  - Long noncoding RNAs (lncRNAs) interact with protein factors to regulate different
      layers of gene expression transcriptionally or posttranscriptionally. Here we
      report on the functional consequences of the unanticipated interaction of the RNA
      binding protein K homology-type splicing regulatory protein (KSRP) with the H19
      lncRNA (H19). KSRP directly binds to H19 in the cytoplasm of undifferentiated
      multipotent mesenchymal C2C12 cells, and this interaction favors KSRP-mediated
      destabilization of labile transcripts such as myogenin. AKT activation induces
      KSRP dismissal from H19 and, as a consequence, myogenin mRNA is stabilized while
      KSRP is repurposed to promote maturation of myogenic microRNAs, thus favoring
      myogenic differentiation. Our data indicate that H19 operates as a molecular
      scaffold that facilitates effective association of KSRP with myogenin and other
      labile transcripts, and we propose that H19 works with KSRP to optimize an AKT
      regulated posttranscriptional switch that controls myogenic differentiation. 

PMID- 25385581
TI  - Spiral precipitation patterns in confined chemical gardens.
AB  - Chemical gardens are mineral aggregates that grow in three dimensions with plant
      like forms and share properties with self-assembled structures like nanoscale
      tubes, brinicles, or chimneys at hydrothermal vents. The analysis of their shapes
      remains a challenge, as their growth is influenced by osmosis, buoyancy, and
      reaction-diffusion processes. Here we show that chemical gardens grown by
      injection of one reactant into the other in confined conditions feature a wealth
      of new patterns including spirals, flowers, and filaments. The confinement
      decreases the influence of buoyancy, reduces the spatial degrees of freedom, and
      allows analysis of the patterns by tools classically used to analyze 2D patterns.
      Injection moreover allows the study in controlled conditions of the effects of
      variable concentrations on the selected morphology. We illustrate these
      innovative aspects by characterizing quantitatively, with a simple geometrical
      model, a new class of self-similar logarithmic spirals observed in a large zone
      of the parameter space. 

PMID- 25385580
TI  - Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity
      to articular cartilage.
AB  - Diarthrodial joints are essential for load bearing and locomotion.
      Physiologically, articular cartilage sustains millions of cycles of mechanical
      loading. Chondrocytes, the cells in cartilage, regulate their metabolic
      activities in response to mechanical loading. Pathological mechanical stress can
      lead to maladaptive cellular responses and subsequent cartilage degeneration. We
      sought to deconstruct chondrocyte mechanotransduction by identifying
      mechanosensitive ion channels functioning at injurious levels of strain. We
      detected robust expression of the recently identified mechanosensitive channels,
      PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained
      potentiated mechanically induced Ca(2+) signals and electrical currents compared
      with single-Piezo expression. In primary articular chondrocytes, mechanically
      evoked Ca(2+) transients produced by atomic force microscopy were inhibited by
      GsMTx4, a PIEZO-blocking peptide, and by Piezo1- or Piezo2-specific siRNA. We
      complemented the cellular approach with an explant-cartilage injury model. GsMTx4
      reduced chondrocyte death after mechanical injury, suggesting a possible therapy
      for reducing cartilage injury and posttraumatic osteoarthritis by attenuating
      Piezo-mediated cartilage mechanotransduction of injurious strains. 

PMID- 25385582
TI  - DNA methylation of BDNF as a biomarker of early-life adversity.
AB  - Early-life adversity increases the risk for psychopathology in later life. The
      underlying mechanism(s) is unknown, but epigenetic variation represents a
      plausible candidate. Early-life exposures can disrupt epigenetic programming in
      the brain, with lasting consequences for gene expression and behavior. This
      evidence is primarily derived from animal studies, with limited study in humans
      due to inaccessibility of the target brain tissue. In humans, although there is
      evidence for DNA methylation changes in the peripheral blood of psychiatric
      patients, a fundamental question remains as to whether epigenetic markers in the
      blood can predict epigenetic changes occurring in the brain. We used in utero
      bisphenol A (BPA) exposure as a model environmental exposure shown to disrupt
      neurodevelopment and exert long-term effects on behavior in animals and humans.
      We show that prenatal BPA induces lasting DNA methylation changes in the
      transcriptionally relevant region of the Bdnf gene in the hippocampus and blood
      of BALB/c mice and that these changes are consistent with BDNF changes in the
      cord blood of humans exposed to high maternal BPA levels in utero. Our data
      suggest that BDNF DNA methylation in the blood may be used as a predictor of
      brain BDNF DNA methylation and gene expression as well as behavioral
      vulnerability induced by early-life environmental exposure. Because BDNF
      expression and DNA methylation are altered in several psychiatric disorders that
      are associated with early-life adversity, including depression, schizophrenia,
      bipolar disorder, and autism, BDNF DNA methylation in the blood may represent a
      novel biomarker for the early detection of psychopathology. 

PMID- 25385583
TI  - Input-specific maturation of synaptic dynamics of parvalbumin interneurons in
      primary visual cortex.
AB  - Cortical networks consist of local recurrent circuits and long-range pathways
      from other brain areas. Parvalbumin-positive interneurons (PVNs) regulate the
      dynamic operation of local ensembles as well as the temporal precision of
      afferent signals. The synaptic recruitment of PVNs that support these circuit
      operations is not well-understood. Here we demonstrate that the synaptic dynamics
      of PVN recruitment in mouse visual cortex are customized according to input
      source with distinct maturation profiles. Whereas the long-range inputs to PVNs
      show strong short-term depression throughout postnatal maturation, local inputs
      from nearby pyramidal neurons progressively lose such depression. This enhanced
      local recruitment depends on PVN-mediated reciprocal inhibition and results from
      both pre- and postsynaptic mechanisms, including calcium-permeable AMPA receptors
      at PVN postsynaptic sites. Although short-term depression of long-range inputs is
      well-suited for afferent signal detection, the robust dynamics of local inputs
      may facilitate rapid and proportional PVN recruitment in regulating local circuit
      operations. 

PMID- 25385584
TI  - Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation
      by nonsteroidal antiinflammatory drugs.
AB  - The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be
      influenced by interactions with antiplatelet doses of aspirin. We sought to
      quantitate precisely the propensity of commonly consumed NSAIDs-ibuprofen,
      naproxen, and celecoxib-to cause a drug-drug interaction with aspirin in vivo by
      measuring the target engagement of aspirin directly by MS. We developed a novel
      assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from
      volunteers who were administered aspirin and used conventional and microfluidic
      assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib
      all had the potential to compete with the access of aspirin to the substrate
      binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic
      dose of each NSAID followed by 325 mg aspirin revealed a potent drug-drug
      interaction between ibuprofen and aspirin and between naproxen and aspirin but
      not between celecoxib and aspirin. The imprecision of estimates of aspirin
      consumption and the differential impact on the ability of aspirin to inactivate
      platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in
      ongoing clinical studies designed to measure their cardiovascular risk.

PMID- 25385585
TI  - Interacting cytoplasmic loops of subunits a and c of Escherichia coli F1F0 ATP
      synthase gate H+ transport to the cytoplasm.
AB  - H(+)-transporting F1F0 ATP synthase catalyzes the synthesis of ATP via coupled
      rotary motors within F0 and F1. H(+) transport at the subunit a-c interface in
      transmembranous F0 drives rotation of a cylindrical c10 oligomer within the
      membrane, which is coupled to rotation of subunit gamma within the alpha3beta3
      sector of F1 to mechanically drive ATP synthesis. F1F0 functions in a reversible
      manner, with ATP hydrolysis driving H(+) transport. ATP-driven H(+) transport in
      a select group of cysteine mutants in subunits a and c is inhibited after
      chelation of Ag(+) and/or Cd(+2) with the substituted sulfhydryl groups. The H(+)
      transport pathway mapped via these Ag(+)(Cd(+2))-sensitive Cys extends from the
      transmembrane helices (TMHs) of subunits a and c into cytoplasmic loops
      connecting the TMHs, suggesting these loop regions could be involved in gating
      H(+) release to the cytoplasm. Here, using select loop-region Cys from the single
      cytoplasmic loop of subunit c and multiple cytoplasmic loops of subunit a, we
      show that Cd(+2) directly inhibits passive H(+) transport mediated by F0
      reconstituted in liposomes. Further, in extensions of previous studies, we show
      that the regions mediating passive H(+) transport can be cross-linked to each
      other. We conclude that the loop-regions in subunits a and c that are implicated
      in H(+) transport likely interact in a single structural domain, which then
      functions in gating H(+) release to the cytoplasm. 

PMID- 25385586
TI  - Bispecific antibody generated with sortase and click chemistry has broad
      antiinfluenza virus activity.
AB  - Bispecific antibodies have therapeutic potential by expanding the functions of
      conventional antibodies. Many different formats of bispecific antibodies have
      meanwhile been developed. Most are genetic modifications of the antibody backbone
      to facilitate incorporation of two different variable domains into a single
      molecule. Here, we present a bispecific format where we have fused two full-sized
      IgG antibodies via their C termini using sortase transpeptidation and click
      chemistry to create a covalently linked IgG antibody heterodimer. By linking two
      potent anti-influenza A antibodies together, we have generated a full antibody
      dimer with bispecific activity that retains the activity and stability of the two
      fusion partners. 

PMID- 25385587
TI  - Potential function for the Huntingtin protein as a scaffold for selective
      autophagy.
AB  - Although dominant gain-of-function triplet repeat expansions in the Huntingtin
      (HTT) gene are the underlying cause of Huntington disease (HD), understanding the
      normal functions of nonmutant HTT protein has remained a challenge. We report
      here findings that suggest that HTT plays a significant role in selective
      autophagy. Loss of HTT function in Drosophila disrupts starvation-induced
      autophagy in larvae and conditional knockout of HTT in the mouse CNS causes
      characteristic cellular hallmarks of disrupted autophagy, including an
      accumulation of striatal p62/SQSTM1 over time. We observe that specific domains
      of HTT have structural similarities to yeast Atg proteins that function in
      selective autophagy, and in particular that the C-terminal domain of HTT shares
      structural similarity to yeast Atg11, an autophagic scaffold protein. To explore
      possible functional similarity between HTT and Atg11, we investigated whether the
      C-terminal domain of HTT interacts with mammalian counterparts of yeast Atg11
      interacting proteins. Strikingly, this domain of HTT coimmunoprecipitates with
      several key Atg11 interactors, including the Atg1/Unc-51-like autophagy
      activating kinase 1 kinase complex, autophagic receptor proteins, and mammalian
      Atg8 homologs. Mutation of a phylogenetically conserved WXXL domain in a C
      terminal HTT fragment reduces coprecipitation with mammalian Atg8 homolog
      GABARAPL1, suggesting a direct interaction. Collectively, these data support a
      possible central role for HTT as an Atg11-like scaffold protein. These findings
      have relevance to both mechanisms of disease pathogenesis and to therapeutic
      intervention strategies that reduce levels of both mutant and normal HTT. 

PMID- 25385588
TI  - The Runt-related transcription factor 1 in prostate cancer-associated
      fibroblasts.

PMID- 25385589
TI  - Follicle-stimulating hormone regulates expression and activity of epidermal
      growth factor receptor in the murine ovarian follicle.
AB  - Fertility depends on the precise coordination of multiple events within the
      ovarian follicle to ensure ovulation of a fertilizable egg. FSH promotes late
      follicular development, including expression of luteinizing hormone (LH) receptor
      by the granulosa cells. Expression of its receptor permits the subsequent LH
      surge to trigger the release of ligands that activate EGF receptors (EGFR) on the
      granulosa, thereby initiating the ovulatory events. Here we identify a previously
      unknown role for FSH in this signaling cascade. We show that follicles of Fshb(-/
      ) mice, which cannot produce FSH, have a severely impaired ability to support two
      essential EGFR-regulated events: expansion of the cumulus granulosa cell layer
      that encloses the oocyte and meiotic maturation of the oocyte. These defects are
      not caused by an inability of Fshb(-/-) oocytes to produce essential oocyte
      secreted factors or of Fshb(-/-) cumulus cells to respond. In contrast, although
      expression of both Egfr and EGFR increases during late folliculogenesis in
      Fshb(+/-) females, these increases fail to occur in Fshb(-/-) females.
      Remarkably, supplying a single dose of exogenous FSH activity to Fshb(-/-)
      females is sufficient to increase Egfr and EGFR expression and to restore EGFR
      dependent cumulus expansion and oocyte maturation. These studies show that FSH
      induces an increase in EGFR expression during late folliculogenesis and provide
      evidence that the FSH-dependent increase is necessary for EGFR physiological
      function. Our results demonstrate an unanticipated role for FSH in establishing
      the signaling axis that coordinates ovulatory events and may contribute to the
      diagnosis and treatment of some types of human infertility. 

PMID- 25385590
TI  - Action video game play facilitates the development of better perceptual
      templates.
AB  - The field of perceptual learning has identified changes in perceptual templates
      as a powerful mechanism mediating the learning of statistical regularities in our
      environment. By measuring threshold-vs.-contrast curves using an orientation
      identification task under varying levels of external noise, the perceptual
      template model (PTM) allows one to disentangle various sources of signal-to-noise
      changes that can alter performance. We use the PTM approach to elucidate the
      mechanism that underlies the wide range of improvements noted after action video
      game play. We show that action video game players make use of improved perceptual
      templates compared with nonvideo game players, and we confirm a causal role for
      action video game play in inducing such improvements through a 50-h training
      study. Then, by adapting a recent neural model to this task, we demonstrate how
      such improved perceptual templates can arise from reweighting the connectivity
      between visual areas. Finally, we establish that action gamers do not enter the
      perceptual task with improved perceptual templates. Instead, although performance
      in action gamers is initially indistinguishable from that of nongamers, action
      gamers more rapidly learn the proper template as they experience the task. Taken
      together, our results establish for the first time to our knowledge the
      development of enhanced perceptual templates following action game play. Because
      such an improvement can facilitate the inference of the proper generative model
      for the task at hand, unlike perceptual learning that is quite specific, it thus
      elucidates a general learning mechanism that can account for the various
      behavioral benefits noted after action game play. 

PMID- 25385591
TI  - Brothers in arms: Libyan revolutionaries bond like family.
AB  - What motivates ordinary civilians to sacrifice their lives for revolutionary
      causes? We surveyed 179 Libyan revolutionaries during the 2011 conflict in Libya.
      These civilians-turned-fighters rejected Gaddafi's jamahiriyya (state of the
      masses) and formed highly cohesive fighting units typical of intense conflicts.
      Fighters reported high levels of "identity fusion"--visceral, family-like bonds
      between fighters and their battalions. Fusion of revolutionaries with their local
      battalions and their own families were extremely high, especially relative to
      Libyans who favored the revolution but did not join battalions. Additionally,
      frontline combatants were as strongly bonded to their battalion as they were to
      their own families, but battalion members who provided logistical support were
      more fused with their families than battalions. Together, these findings help
      illuminate the social bonds that seem to motivate combatants to risk their lives
      for the group during wartime.

PMID- 25385593
TI  - Targeted carbon conservation at national scales with high-resolution monitoring.
AB  - Terrestrial carbon conservation can provide critical environmental, social, and
      climate benefits. Yet, the geographically complex mosaic of threats to, and
      opportunities for, conserving carbon in landscapes remain largely unresolved at
      national scales. Using a new high-resolution carbon mapping approach applied to
      Peru, a megadiverse country undergoing rapid land use change, we found that at
      least 0.8 Pg of aboveground carbon stocks are at imminent risk of emission from
      land use activities. Map-based information on the natural controls over carbon
      density, as well as current ecosystem threats and protections, revealed three
      biogeographically explicit strategies that fully offset forthcoming land-use
      emissions. High-resolution carbon mapping affords targeted interventions to
      reduce greenhouse gas emissions in rapidly developing tropical nations. 

PMID- 25385594
TI  - Selective degeneration of a physiological subtype of spinal motor neuron in mice
      with SOD1-linked ALS.
AB  - Amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease) affects motor neurons
      (MNs) in the brain and spinal cord. Understanding the pathophysiology of this
      condition seems crucial for therapeutic design, yet few electrophysiological
      studies in actively degenerating animal models have been reported. Here, we
      report a novel preparation of acute slices from adult mouse spinal cord, allowing
      visualized whole cell patch-clamp recordings of fluorescent lumbar MN cell bodies
      from ChAT-eGFP or superoxide dismutase 1-yellow fluorescent protein (SOD1YFP)
      transgenic animals up to 6 mo of age. We examined 11 intrinsic electrophysiologic
      properties of adult ChAT-eGFP mouse MNs and classified them into four subtypes
      based on these parameters. The subtypes could be principally correlated with
      instantaneous (initial) and steady-state firing rates. We used retrograde tracing
      using fluorescent dye injected into fast or slow twitch lower extremity muscle
      with slice recordings from the fluorescent-labeled lumbar MN cell bodies to
      establish that fast and slow firing MNs are connected with fast and slow twitch
      muscle, respectively. In a G85R SOD1YFP transgenic mouse model of ALS, which
      becomes paralyzed by 5-6 mo, where MN cell bodies are fluorescent, enabling the
      same type of recording from spinal cord tissue slices, we observed that all four
      MN subtypes were present at 2 mo of age. At 4 mo, by which time substantial
      neuronal SOD1YFP aggregation and cell loss has occurred and symptoms have
      developed, one of the fast firing subtypes that innvervates fast twitch muscle
      was lost. These results begin to describe an order of the pathophysiologic events
      in ALS. 

PMID- 25385595
TI  - Peptide and small molecule inhibitors of HECT-type ubiquitin ligases.
AB  - The human genome encodes several hundred E3 ubiquitin ligases containing RING
      domains, and around 28 containing HECT domains. These enzymes catalyze the
      transfer of ubiquitin from E2 enzyme thioesters to a huge range of substrates and
      play crucial roles in many cellular functions. This makes them attractive
      potential therapeutic targets. However, they have proven difficult to inhibit:
      very few good inhibitors exist for RING domain ligases, and none have been
      described for HECT ligases. Here we show that bicyclic peptides isolated by phage
      display [Heinis C, Rutherford T, Freund S, Winter G (2009) Nat Chem Biol.
      5(7):502-507] can target the E2 binding sites on the HECT domains of Smurf2,
      Nedd4, Mule/Huwe1, and WWP1, and thus act as specific inhibitors of these enzymes
      in vitro. By screening for displacement of one of these peptides from Smurf2, we
      were able to identify a small molecule, heclin (HECT ligase inhibitor), which
      inhibits several HECT ligases in tissue culture cells. In vitro, heclin does not
      block E2 binding but causes a conformational change that results in oxidation of
      the active site Cys. This demonstrates that HECT domains are potentially
      druggable and provides molecules that may be of experimental use. Heclin kills
      HEK293 cells growing in culture, consistent with an essential role for HECT
      ligase activity in mammalian cells. 

PMID- 25385596
TI  - Epstein-Barr virus replicating in epithelial cells.

PMID- 25385597
TI  - Reversals of national fortune, and social science methodologies.
AB  - Among non-European regions colonized by Europeans, regions that were relatively
      richer five centuries ago (like Mexico, Peru, and India) tend to be poorer today,
      while regions that originally were relatively poorer (like the United States,
      Chile, and Australia) tend now to be richer. Acemoglu, Johnson, and Robinson
      (abbreviated AJR) established the generality of this reversal of fortune. Chanda,
      Cook, and Putterman (abbreviated CCP) have now reanalyzed it, taking as a unit of
      analysis populations rather than geographic regions. That is, India's population
      was Indian 500 y ago and is still overwhelmingly Indian today, whereas the United
      States' population was Native American 500 years ago but is overwhelmingly Old
      World (especially European) today. Reversals of fortune disappeared when CCP
      analyzed populations rather than geographic regions: for instance, the geographic
      region of the modern United States has become relatively richer since AD 1500,
      but the predominantly European population now occupying the United States was
      already relatively rich in AD 1500. Evidently, European colonists carried
      ingredients of wealth with them. I discuss the biological and cultural baggage
      transported by European immigrants and associated with wealth. Among that
      baggage, AJR emphasize institutions, CCP emphasize social capital, and I identify
      many different elements only loosely coupled to each other. This paper discusses
      the problem, especially acute in the social sciences, of "operationalizing"
      intuitive concepts (such as mass, temperature, wealth, and innovation) so that
      they can be measured. Basic concepts tend to be harder to define, operationalize,
      and measure in the social sciences than in the laboratory sciences. 

PMID- 25385598
TI  - Neurite outgrowth induced by NGF or L1CAM via activation of the TrkA receptor is
      sustained also by the exocytosis of enlargeosomes.
AB  - NGF binding to its protein kinase receptor TrkA is known to induce neurite
      outgrowth and neural cell differentiation. The plasma membrane expansion,
      necessary for the process, was shown to be contributed by the VAMP7-dependent
      exocytosis of endocytic vesicles. Working with wild-type PC12 (wtPC12), a cell
      model widely used to investigate NGF-induced neurite outgrowth, we found that a
      few hours of treatment with the neurotrophin (and to a lower extent with basic
      FGF and EGF) induces the appearance of enlargeosome vesicles competent for VAMP4
      dependent exocytosis abundant in high REST-PC12 clones. Both the neurite length
      assay and the immunocytochemistry of enlargeosomes exocytosis revealed that
      activation of TrkA is induced not only by NGF, but also by the L1 adhesion
      protein, L1CAM, whose soluble construct binds the receptor with submicromolar
      affinity. In the intact wtPC12, the L1CAM construct induced autophosphorylation
      and internalization of TrkA followed by the activation of the PI3K, MEK, and
      PKCgamma signaling cascades, analogous to the responses induced by NGF. Down
      regulation of either VAMP7 or VAMP4 revealed the coparticipation of the two
      corresponding vesicles to the outgrowth responses induced by NGF and L1CAM.
      Finally, mixing experiments of wtPC12 cells rich in TrkA with high REST PC12
      cells transfected with L1CAM documented the transactivation of the receptor by
      the adhesion protein surface-exposed in adjacent cells. In view of the known
      inhomogeneous surface distribution of both L1CAM and TrkA in various neural cells
      including neurons, their transcellular binding could be restricted to discrete
      sites, governing local signaling events distinct from those induced by soluble
      messengers. 

PMID- 25385599
TI  - New insights into Eastern Beringian mortuary behavior: a terminal Pleistocene
      double infant burial at Upward Sun River.
AB  - Here we report on the discovery of two infant burials dating to ~11,500
      calibrated years (cal) B.P. at the Upward Sun River site in central Alaska. The
      infants were interred in a pit feature with associated organic and lithic grave
      goods, including the earliest known North American hafted bifaces with decorated
      antler foreshafts. Skeletal and dental analyses indicate that Individual 1 died
      shortly after birth and Individual 2 was a late-term fetus, making these the
      youngest-aged late Pleistocene individuals known for the Americas and the only
      known prenate, offering, to our knowledge, the first opportunity to explore
      mortuary treatment of the youngest members of a terminal Pleistocene North
      American population. This burial was situated ~40 cm directly below a cremated 3
      y-old child previously discovered in association with a central hearth of a
      residential feature. The burial and cremation are contemporaneous, and
      differences in body orientation, treatment, and associated grave goods within a
      single feature and evidence for residential occupation between burial episodes
      indicate novel mortuary behaviors. The human remains, grave goods, and associated
      fauna provide rare direct data on organic technology, economy, seasonality of
      residential occupations, and infant/child mortality of terminal Pleistocene
      Beringians. 

PMID- 25385592
TI  - Comparative analysis of the domestic cat genome reveals genetic signatures
      underlying feline biology and domestication.
AB  - Little is known about the genetic changes that distinguish domestic cat
      populations from their wild progenitors. Here we describe a high-quality domestic
      cat reference genome assembly and comparative inferences made with other cat
      breeds, wildcats, and other mammals. Based upon these comparisons, we identified
      positively selected genes enriched for genes involved in lipid metabolism that
      underpin adaptations to a hypercarnivorous diet. We also found positive selection
      signals within genes underlying sensory processes, especially those affecting
      vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff
      between functional olfactory and vomeronasal receptor gene repertoires in the cat
      and dog genomes, with an expansion of the feline chemosensory system for
      detecting pheromones at the expense of odorant detection. Genomic regions
      harboring signatures of natural selection that distinguish domestic cats from
      their wild congeners are enriched in neural crest-related genes associated with
      behavior and reward in mouse models, as predicted by the domestication syndrome
      hypothesis. Our description of a previously unidentified allele for the gloving
      pigmentation pattern found in the Birman breed supports the hypothesis that cat
      breeds experienced strong selection on specific mutations drawn from random bred
      populations. Collectively, these findings provide insight into how the process of
      domestication altered the ancestral wildcat genome and build a resource for
      future disease mapping and phylogenomic studies across all members of the
      Felidae. 

PMID- 25385600
TI  - Synchronized renal tubular cell death involves ferroptosis.
AB  - Receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is thought to
      be the pathophysiologically predominant pathway that leads to regulated necrosis
      of parenchymal cells in ischemia-reperfusion injury (IRI), and loss of either Fas
      associated protein with death domain (FADD) or caspase-8 is known to sensitize
      tissues to undergo spontaneous necroptosis. Here, we demonstrate that renal
      tubules do not undergo sensitization to necroptosis upon genetic ablation of
      either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does
      not protect freshly isolated tubules from hypoxic injury. In contrast, iron
      dependent ferroptosis directly causes synchronized necrosis of renal tubules, as
      demonstrated by intravital microscopy in models of IRI and oxalate crystal
      induced acute kidney injury. To suppress ferroptosis in vivo, we generated a
      novel third-generation ferrostatin (termed 16-86), which we demonstrate to be
      more stable, to metabolism and plasma, and more potent, compared with the first
      in-class compound ferrostatin-1 (Fer-1). Even in conditions with extraordinarily
      severe IRI, 16-86 exerts strong protection to an extent which has not previously
      allowed survival in any murine setting. In addition, 16-86 further potentiates
      the strong protective effect on IRI mediated by combination therapy with
      necrostatins and compounds that inhibit mitochondrial permeability transition.
      Renal tubules thus represent a tissue that is not sensitized to necroptosis by
      loss of FADD or caspase-8. Finally, ferroptosis mediates postischemic and toxic
      renal necrosis, which may be therapeutically targeted by ferrostatins and by
      combination therapy. 

PMID- 25385602
TI  - Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment
      packaging while enhancing viral fitness and transmissibility.
AB  - The influenza A virus (IAV) genome is divided into eight distinct RNA segments
      believed to be copackaged into virions with nearly perfect efficiency. Here, we
      describe a mutation in IAV nucleoprotein (NP) that enhances replication and
      transmission in guinea pigs while selectively reducing neuraminidase (NA) gene
      segment packaging into virions. We show that incomplete IAV particles lacking
      gene segments contribute to the propagation of the viral population through
      multiplicity reactivation under conditions of widespread coinfection, which we
      demonstrate commonly occurs in the upper respiratory tract of guinea pigs. NP
      also dramatically altered the functional balance of the viral glycoproteins on
      particles by selectively decreasing NA expression. Our findings reveal novel
      functions for NP in selective control of IAV gene packaging and balancing
      glycoprotein expression and suggest a role for incomplete gene packaging during
      host adaptation and transmission. 

PMID- 25385601
TI  - Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human
      T cells via STAT3-dependent mechanism.
AB  - Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory
      cytokines and the development of autoimmunity in mice. Data from a phase 1
      clinical trial demonstrate that oral administration of KD025, a selective ROCK2
      inhibitor, to healthy human subjects down-regulates the ability of T cells to
      secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-gamma in
      response to T-cell receptor stimulation in vitro. Pharmacological inhibition with
      KD025 or siRNA-mediated inhibition of ROCK2, but not ROCK1, significantly
      diminished STAT3 phosphorylation and binding to IL-17 and IL-21 promoters and
      reduced IFN regulatory factor 4 and nuclear hormone RAR-related orphan receptor
      gammat protein levels in T cells derived from healthy subjects or rheumatoid
      arthritis patients. Simultaneously, treatment with KD025 also promotes the
      suppressive function of regulatory T cells through up-regulation of STAT5
      phosphorylation and positive regulation of forkhead box p3 expression. The
      administration of KD025 in vivo down-regulates the progression of collagen
      induced arthritis in mice via targeting of the Th17-mediated pathway. Thus, ROCK2
      signaling appears to be instrumental in regulating the balance between
      proinflammatory and regulatory T-cell subsets. Targeting of ROCK2 in man may
      therefore restore disrupted immune homeostasis and have a role in the treatment
      of autoimmunity. 

PMID- 25385603
TI  - TSG-6 as a biomarker to predict efficacy of human mesenchymal stem/progenitor
      cells (hMSCs) in modulating sterile inflammation in vivo.
AB  - Human mesenchymal stem/progenitor cells (hMSCs) from bone marrow and other
      tissues are currently being administered to large numbers of patients even though
      there are no biomarkers that accurately predict their efficacy in vivo. Using a
      mouse model of chemical injury of the cornea, we found that bone-marrow-derived
      hMSCs isolated from different donors varied widely in their efficacy in
      modulating sterile inflammation. Importantly, RT-PCR assays of hMSCs for the
      inflammation-modulating protein TSG-6 expressed by the TNFalpha-stimulated gene 6
      (TSG-6 or TNFAIP6) predicted their efficacy in sterile inflammation models for
      corneal injury, sterile peritonitis, and bleomycin-induced lung injury. In
      contrast, the levels of TSG-6 mRNA were negatively correlated with their
      potential for osteogenic differentiation in vitro and poorly correlated with
      other criteria for evaluating hMSCs. Also, a survey of a small cohort suggested
      that hMSCs from female donors compared with male donors more effectively
      suppressed sterile inflammation, expressed higher levels of TSG-6, and had
      slightly less osteogenic potential. 

PMID- 25385604
TI  - Complementarity in the provision of ecosystem services reduces the cost of
      mitigating amplified natural disturbance events.
AB  - Climate change has been implicated as a root cause of the recent surge in natural
      disturbance events such as storms, wildfires, and insect outbreaks. This climate
      based surge has led to a greater focus on disturbance-mitigating benefits of
      ecosystem management. Quantifying these benefits requires knowledge of the
      relationship between natural and anthropogenic disturbances, which is lacking at
      the temporal and spatial scales needed to inform ecosystem-based management. This
      study investigates a specific relationship between timber harvesting and climate
      amplified outbreaks of mountain pine beetle. If harvesting is located to mitigate
      long-distance insect dispersal, there is potential for a win-win outcome in which
      both timber production and forest conservation can be increased. This spatially
      targeted harvesting strategy lowers the cost of providing disturbance-mitigating
      ecosystem services, because valuable timber products are also produced.
      Mitigating long-distance dispersal also produces net gains in forest conservation
      across various stakeholder groups. These results speak to ongoing federal efforts
      to encourage forest vegetation removal on public forestlands to improve forest
      health. These efforts will lower the cost of responding to climate-amplified
      natural disturbance events but only if vegetation removal efforts are spatially
      located to reduce disturbance risk. Otherwise, efforts to improve forest health
      may be converting forest conservation services to timber services. 

PMID- 25385605
TI  - The ecology of religious beliefs.
AB  - Although ecological forces are known to shape the expression of sociality across
      a broad range of biological taxa, their role in shaping human behavior is
      currently disputed. Both comparative and experimental evidence indicate that
      beliefs in moralizing high gods promote cooperation among humans, a behavioral
      attribute known to correlate with environmental harshness in nonhuman animals.
      Here we combine fine-grained bioclimatic data with the latest statistical tools
      from ecology and the social sciences to evaluate the potential effects of
      environmental forces, language history, and culture on the global distribution of
      belief in moralizing high gods (n = 583 societies). After simultaneously
      accounting for potential nonindependence among societies because of shared
      ancestry and cultural diffusion, we find that these beliefs are more prevalent
      among societies that inhabit poorer environments and are more prone to ecological
      duress. In addition, we find that these beliefs are more likely in politically
      complex societies that recognize rights to movable property. Overall, our
      multimodel inference approach predicts the global distribution of beliefs in
      moralizing high gods with an accuracy of 91%, and estimates the relative
      importance of different potential mechanisms by which this spatial pattern may
      have arisen. The emerging picture is neither one of pure cultural transmission
      nor of simple ecological determinism, but rather a complex mixture of social,
      cultural, and environmental influences. Our methods and findings provide a
      blueprint for how the increasing wealth of ecological, linguistic, and historical
      data can be leveraged to understand the forces that have shaped the behavior of
      our own species. 

PMID- 25385606
TI  - Optic flow instructs retinotopic map formation through a spatial to temporal to
      spatial transformation of visual information.
AB  - Retinotopic maps are plastic in response to changes in sensory input; however,
      the experience-dependent instructive cues that organize retinotopy are unclear.
      In animals with forward-directed locomotion, the predominant anterior to
      posterior optic flow activates retinal ganglion cells in a stereotyped temporal
      to nasal sequence. Here we imaged retinotectal axon arbor location and structural
      plasticity to assess map refinement in vivo while exposing Xenopus tadpoles to
      visual stimuli. We show that the temporal sequence of retinal activity driven by
      natural optic flow organizes retinotopy by regulating axon arbor branch dynamics,
      whereas the opposite sequence of retinal activity prevents map refinement. Our
      study demonstrates that a spatial to temporal to spatial transformation of visual
      information controls experience-dependent topographic map plasticity. This
      organizational principle is likely to apply to other sensory modalities and
      projections in the brain. 

PMID- 25385607
TI  - Spaced training rescues memory and ERK1/2 signaling in fragile X syndrome model
      mice.
AB  - Recent studies have shown that short, spaced trains of afferent stimulation
      produce much greater long-term potentiation (LTP) than that obtained with a
      single, prolonged stimulation episode. The present studies demonstrate that
      spaced training regimens, based on these LTP timing rules, facilitate learning in
      wild-type (WT) mice and can offset learning and synaptic signaling impairments in
      the fragile X mental retardation 1 (Fmr1) knockout (KO) model of fragile X
      syndrome. We determined that 5 min of continuous training supports object
      location memory (OLM) in WT but not Fmr1 KO mice. However, the same amount of
      training distributed across three short trials, spaced by one hour, produced
      robust long-term memory in the KOs. At least three training trials were needed to
      realize the benefit of spacing, and intertrial intervals shorter or longer than
      60 min were ineffective. Multiple short training trials also rescued novel object
      recognition in Fmr1 KOs. The spacing effect was surprisingly potent: just 1 min
      of OLM training, distributed across three trials, supported robust memory in both
      genotypes. Spacing also rescued training-induced activation of synaptic ERK1/2 in
      dorsal hippocampus of Fmr1 KO mice. These results show that a spaced training
      regimen designed to maximize synaptic potentiation facilitates recognition memory
      in WT mice and can offset synaptic signaling and memory impairments in a model of
      congenital intellectual disability. 

PMID- 25385608
TI  - In vitro evolution of high-titer, virus-like vesicles containing a single
      structural protein.
AB  - Self-propagating, infectious, virus-like vesicles (VLVs) are generated when an
      alphavirus RNA replicon expresses the vesicular stomatitis virus glycoprotein
      (VSV G) as the only structural protein. The mechanism that generates these VLVs
      lacking a capsid protein has remained a mystery for over 20 years. We present
      evidence that VLVs arise from membrane-enveloped RNA replication factories
      (spherules) containing VSV G protein that are largely trapped on the cell
      surface. After extensive passaging, VLVs evolve to grow to high titers through
      acquisition of multiple point mutations in their nonstructural replicase
      proteins. We reconstituted these mutations into a plasmid-based system from which
      high-titer VLVs can be recovered. One of these mutations generates a late domain
      motif (PTAP) that is critical for high-titer VLV production. We propose a model
      in which the VLVs have evolved in vitro to exploit a cellular budding pathway
      that is hijacked by many enveloped viruses, allowing them to bud efficiently from
      the cell surface. Our results suggest a basic mechanism of propagation that may
      have been used by primitive RNA viruses lacking capsid proteins. Capsids may have
      evolved later to allow more efficient packaging of RNA, greater virus stability,
      and evasion of innate immunity. 

PMID- 25385610
TI  - Multifunctional supramolecular polymer networks as next-generation consolidants
      for archaeological wood conservation.
AB  - The preservation of our cultural heritage is of great importance to future
      generations. Despite this, significant problems have arisen with the conservation
      of waterlogged wooden artifacts. Three major issues facing conservators are
      structural instability on drying, biological degradation, and chemical
      degradation on account of Fe(3+)-catalyzed production of sulfuric and oxalic acid
      in the waterlogged timbers. Currently, no conservation treatment exists that
      effectively addresses all three issues simultaneously. A new conservation
      treatment is reported here based on a supramolecular polymer network constructed
      from natural polymers with dynamic cross-linking formed by a combination of both
      host-guest complexation and a strong siderophore pendant from a polymer backbone.
      Consequently, the proposed consolidant has the ability to chelate and trap iron
      while enhancing structural stability. The incorporation of antibacterial moieties
      through a dynamic covalent linkage into the network provides the material with
      improved biological resistance. Exploiting an environmentally compatible natural
      material with completely reversible chemistries is a safer, greener alternative
      to current strategies and may extend the lifetime of many culturally relevant
      waterlogged artifacts around the world. 

PMID- 25385609
TI  - Stress and the dynamic genome: Steroids, epigenetics, and the transposome.
AB  - Stress plays a substantial role in shaping behavior and brain function, often
      with lasting effects. How these lasting effects occur in the context of a fixed
      postmitotic neuronal genome has been an enduring question for the field. Synaptic
      plasticity and neurogenesis have provided some of the answers to this question,
      and more recently epigenetic mechanisms have come to the fore. The exploration of
      epigenetic mechanisms recently led us to discover that a single acute stress can
      regulate the expression of retrotransposons in the rat hippocampus via an
      epigenetic mechanism. We propose that this response may represent a genomic
      stress response aimed at maintaining genomic and transcriptional stability in
      vulnerable brain regions such as the hippocampus. This finding and those of other
      researchers have made clear that retrotransposons and the genomic plasticity they
      permit play a significant role in brain function during stress and disease. These
      observations also raise the possibility that the transposome might have adaptive
      functions at the level of both evolution and the individual organism. 

PMID- 25385612
TI  - Historical distribution of Sundaland's Dipterocarp rainforests at Quaternary
      glacial maxima.
AB  - The extent of Dipterocarp rainforests on the emergent Sundaland landmass in
      Southeast Asia during Quaternary glaciations remains a key question. A better
      understanding of the biogeographic history of Sundaland could help explain
      current patterns of biodiversity and support the development of effective forest
      conservation strategies. Dipterocarpaceae trees dominate the rainforests of
      Sundaland, and their distributions serve as a proxy for rainforest extent. We
      used species distribution models (SDMs) of 317 Dipterocarp species to estimate
      the geographic extent of appropriate climatic conditions for rainforest on
      Sundaland at the last glacial maximum (LGM). The SDMs suggest that the climate of
      central Sundaland at the LGM was suitable to sustain Dipterocarp rainforest, and
      that the presence of a previously suggested transequatorial savannah corridor at
      that time is unlikely. Our findings are supported by palynologic evidence,
      dynamic vegetation models, extant mammal and termite communities, vascular plant
      fatty acid stable isotopic compositions, and stable carbon isotopic compositions
      of cave guano profiles. Although Dipterocarp species richness was generally lower
      at the LGM, areas of high species richness were mostly found off the current
      islands and on the emergent Sunda Shelf, indicating substantial species migration
      and mixing during the transitions between the Quaternary glacial maxima and warm
      periods such as the present. 

PMID- 25385611
TI  - Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a
      highly specific assembly mechanism for the apical Crumbs complex.
AB  - The Crumbs (Crb) complex, formed by Crb, PALS1, and PATJ, is evolutionarily
      conserved in metazoans and acts as a master cell-growth and -polarity regulator
      at the apical membranes in polarized epithelia. Crb intracellular functions,
      including its direct binding to PALS1, are mediated by Crb's highly conserved 37
      residue cytoplasmic tail. However, the mechanistic basis governing the highly
      specific Crb-PALS1 complex formation is unclear, as reported interaction between
      the Crb tail (Crb-CT) and PALS1 PSD-95/DLG/ZO-1 (PDZ) domain is weak and
      promiscuous. Here we have discovered that the PDZ-Src homolgy 3 (SH3)-Guanylate
      kinase (GK) tandem of PALS1 binds to Crb-CT with a dissociation constant of 70
      nM, which is ~ 100-fold stronger than the PALS1 PDZ-Crb-CT interaction. The
      crystal structure of the PALS1 PDZ-SH3-GK-Crb-CT complex reveals that PDZ-SH3-GK
      forms a structural supramodule with all three domains contributing to the tight
      binding to Crb. Mutations disrupting the tertiary interactions of the PDZ-SH3-GK
      supramodule weaken the PALS1-Crb interaction and compromise PALS1-mediated
      polarity establishment in Madin-Darby canine kidney (MDCK) cysts. We further show
      that specific target binding of other members of membrane-associated guanylate
      kinases (MAGUKs) (e.g., CASK binding to neurexin) also requires the presence of
      their PDZ-SH3-GK tandems.

PMID- 25385613
TI  - Spontaneous regeneration of cochlear supporting cells after neonatal ablation
      ensures hearing in the adult mouse.
AB  - Supporting cells in the cochlea play critical roles in the development,
      maintenance, and function of sensory hair cells and auditory neurons. Although
      the loss of hair cells or auditory neurons results in sensorineural hearing loss,
      the consequence of supporting cell loss on auditory function is largely unknown.
      In this study, we specifically ablated inner border cells (IBCs) and inner
      phalangeal cells (IPhCs), the two types of supporting cells surrounding inner
      hair cells (IHCs) in mice in vivo. We demonstrate that the organ of Corti has the
      intrinsic capacity to replenish IBCs/IPhCs effectively during early postnatal
      development. Repopulation depends on the presence of hair cells and cells within
      the greater epithelial ridge and is independent of cell proliferation. This
      plastic response in the neonatal cochlea preserves neuronal survival, afferent
      innervation, and hearing sensitivity in adult mice. In contrast, the capacity for
      IBC/IPhC regeneration is lost in the mature organ of Corti, and consequently IHC
      survival and hearing sensitivity are impaired significantly, demonstrating that
      there is a critical period for the regeneration of cochlear supporting cells. Our
      findings indicate that the quiescent neonatal organ of Corti can replenish
      specific supporting cells completely after loss in vivo to guarantee mature
      hearing function. 

PMID- 25385614
TI  - Targeting the minor pocket of C5aR for the rational design of an oral allosteric
      inhibitor for inflammatory and neuropathic pain relief.
AB  - Chronic pain resulting from inflammatory and neuropathic disorders causes
      considerable economic and social burden. Pharmacological therapies currently
      available for certain types of pain are only partially effective and may cause
      severe adverse side effects. The C5a anaphylatoxin acting on its cognate G
      protein-coupled receptor (GPCR), C5aR, is a potent pronociceptive mediator in
      several models of inflammatory and neuropathic pain. Although there has long been
      interest in the identification of C5aR inhibitors, their development has been
      complicated, as for many peptidomimetic drugs, mostly by poor drug-like
      properties. Herein, we report the de novo design of a potent and selective C5aR
      noncompetitive allosteric inhibitor, DF2593A, guided by the hypothesis that an
      allosteric site, the "minor pocket," previously characterized in CXC chemokine
      receptors-1 and -2, is functionally conserved in the GPCR class. In vitro,
      DF2593A potently inhibited C5a-induced migration of human and rodent neutrophils.
      In vivo, oral administration of DF2593A effectively reduced mechanical
      hyperalgesia in several models of acute and chronic inflammatory and neuropathic
      pain, without any apparent side effects. Mechanical hyperalgesia after spared
      nerve injury was also reduced in C5aR(-/-) mice compared with WT mice.
      Furthermore, treatment of C5aR(-/-) mice with DF2593A did not produce any further
      antinociceptive effect compared with C5aR(-/-) mice treated with vehicle. The
      successful medicinal chemistry strategy confirms that a conserved minor pocket is
      amenable for the rational design of selective inhibitors and the pharmacological
      results support that the allosteric blockade of the C5aR represents a highly
      promising therapeutic approach to control chronic inflammatory and neuropathic
      pain. 

PMID- 25385615
TI  - The pathogen Batrachochytrium dendrobatidis disturbs the frog skin microbiome
      during a natural epidemic and experimental infection.
AB  - Symbiotic microbial communities may interact with infectious pathogens sharing a
      common host. The microbiome may limit pathogen infection or, conversely, an
      invading pathogen can disturb the microbiome. Documentation of such relationships
      during naturally occurring disease outbreaks is rare, and identifying causal
      links from field observations is difficult. This study documented the effects of
      an amphibian skin pathogen of global conservation concern [the chytrid fungus
      Batrachochytrium dendrobatidis (Bd)] on the skin-associated bacterial microbiome
      of the endangered frog, Rana sierrae, using a combination of population surveys
      and laboratory experiments. We examined covariation of pathogen infection and
      bacterial microbiome composition in wild frogs, demonstrating a strong and
      consistent correlation between Bd infection load and bacterial community
      composition in multiple R. sierrae populations. Despite the correlation between
      Bd infection load and bacterial community composition, we observed 100% mortality
      of postmetamorphic frogs during a Bd epizootic, suggesting that the relationship
      between Bd and bacterial communities was not linked to variation in resistance to
      mortal disease and that Bd infection altered bacterial communities. In a
      controlled experiment, Bd infection significantly altered the R. sierrae
      microbiome, demonstrating a causal relationship. The response of microbial
      communities to Bd infection was remarkably consistent: Several bacterial taxa
      showed the same response to Bd infection across multiple field populations and
      the laboratory experiment, indicating a somewhat predictable interaction between
      Bd and the microbiome. The laboratory experiment demonstrates that Bd infection
      causes changes to amphibian skin bacterial communities, whereas the laboratory
      and field results together strongly support Bd disturbance as a driver of
      bacterial community change during natural disease dynamics. 

PMID- 25385616
TI  - Cross-species genetic exchange between visceral and cutaneous strains of
      Leishmania in the sand fly vector.
AB  - Genetic exchange between Leishmania major strains during their development in the
      sand fly vector has been experimentally shown. To investigate the possibility of
      genetic exchange between different Leishmania species, a cutaneous strain of L.
      major and a visceral strain of Leishmania infantum, each bearing a different drug
      resistant marker, were used to coinfect Lutzomyia longipalpis sand flies. Eleven
      double-drug-resistant progeny clones, each the product of an independent mating
      event, were generated and submitted to genotype and phenotype analyses. The
      analysis of multiple allelic markers across the genome suggested that each
      progeny clone inherited at least one full set of chromosomes from each parent,
      with loss of heterozygosity at some loci, and uniparental retention of maxicircle
      kinetoplast DNA. Hybrids with DNA contents of approximately 2n, 3n, and 4n were
      observed. In vivo studies revealed clear differences in the ability of the
      hybrids to produce pathology in the skin or to disseminate to and grow in the
      viscera, suggesting polymorphisms and differential inheritance of the gene(s)
      controlling these traits. The studies, to our knowledge, represent the first
      experimental confirmation of cross-species mating in Leishmania, opening the way
      toward genetic linkage analysis of important traits and providing strong evidence
      that genetic exchange is responsible for the generation of the mixed-species
      genotypes observed in natural populations. 

PMID- 25385617
TI  - Specific functions of the Wnt signaling system in gene regulatory networks
      throughout the early sea urchin embryo.
AB  - Wnt signaling affects cell-fate specification processes throughout embryonic
      development. Here we take advantage of the well-studied gene regulatory networks
      (GRNs) that control pregastrular sea urchin embryogenesis to reveal the gene
      regulatory functions of the entire Wnt-signaling system. Five wnt genes, three
      frizzled genes, two secreted frizzled-related protein 1 genes, and two Dickkopf
      genes are expressed in dynamic spatial patterns in the pregastrular embryo of
      Strongylocentrotus purpuratus. We present a comprehensive analysis of these genes
      in each embryonic domain. Total functions of the Wnt-signaling system in
      regulatory gene expression throughout the embryo were studied by use of the
      Porcupine inhibitor C59, which interferes with zygotic Wnt ligand secretion.
      Morpholino-mediated knockdown of each expressed Wnt ligand demonstrated that
      individual Wnt ligands are functionally distinct, despite their partially
      overlapping spatial expression. They target specific embryonic domains and affect
      particular regulatory genes. The sum of the effects of blocking expression of
      individual wnt genes is shown to equal C59 effects. Remarkably, zygotic Wnt
      signaling inputs are required for only three general aspects of embryonic
      specification: the broad activation of endodermal GRNs, the regional
      specification of the immediately adjacent stripe of ectoderm, and the restriction
      of the apical neurogenic domain. All Wnt signaling in this pregastrular embryo is
      short range (and/or autocrine). Furthermore, we show that the transcriptional
      drivers of wnt genes execute important specification functions in the embryonic
      domains targeted by the ligands, thus connecting the expression and function of
      wnt genes by encoded cross-regulatory interactions within the specific regional
      GRNs. 

PMID- 25385618
TI  - High-speed odor transduction and pulse tracking by insect olfactory receptor
      neurons.
AB  - Sensory systems encode both the static quality of a stimulus (e.g., color or
      shape) and its kinetics (e.g., speed and direction). The limits with which
      stimulus kinetics can be resolved are well understood in vision, audition, and
      somatosensation. However, the maximum temporal resolution of olfactory systems
      has not been accurately determined. Here, we probe the limits of temporal
      resolution in insect olfaction by delivering high frequency odor pulses and
      measuring sensory responses in the antennae. We show that transduction times and
      pulse tracking capabilities of olfactory receptor neurons are faster than
      previously reported. Once an odorant arrives at the boundary layer of the
      antenna, odor transduction can occur within less than 2 ms and fluctuating odor
      stimuli can be resolved at frequencies more than 100 Hz. Thus, insect olfactory
      receptor neurons can track stimuli of very short duration, as occur when their
      antennae encounter narrow filaments in an odor plume. These results provide a new
      upper bound to the kinetics of odor tracking in insect olfactory receptor neurons
      and to the latency of initial transduction events in olfaction. 

PMID- 25385619
TI  - Sparse sign-consistent Johnson-Lindenstrauss matrices: compression with
      neuroscience-based constraints.
AB  - Johnson-Lindenstrauss (JL) matrices implemented by sparse random synaptic
      connections are thought to be a prime candidate for how convergent pathways in
      the brain compress information. However, to date, there is no complete
      mathematical support for such implementations given the constraints of real
      neural tissue. The fact that neurons are either excitatory or inhibitory implies
      that every so implementable JL matrix must be sign consistent (i.e., all entries
      in a single column must be either all nonnegative or all nonpositive), and the
      fact that any given neuron connects to a relatively small subset of other neurons
      implies that the JL matrix should be sparse. We construct sparse JL matrices that
      are sign consistent and prove that our construction is essentially optimal. Our
      work answers a mathematical question that was triggered by earlier work and is
      necessary to justify the existence of JL compression in the brain and emphasizes
      that inhibition is crucial if neurons are to perform efficient, correlation
      preserving compression. 

PMID- 25385620
TI  - Prediction of interindividual differences in hepatic functions and drug
      sensitivity by using human iPS-derived hepatocytes.
AB  - Interindividual differences in hepatic metabolism, which are mainly due to
      genetic polymorphism in its gene, have a large influence on individual drug
      efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from
      human induced pluripotent stem (iPS) cells have the potential to predict
      interindividual differences in drug metabolism capacity and drug response.
      However, it remains uncertain whether human iPSC-derived HLCs can reproduce the
      interindividual difference in hepatic metabolism and drug response. We found that
      cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary
      human hepatocytes (PHH)-iPS-HLCs were highly correlated with those of PHHs,
      suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity
      and drug responsiveness. We also demonstrated that the interindividual
      differences, which are due to the diversity of individual SNPs in the CYP gene,
      could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our
      knowledge, the first PHH-iPS-HLC panel that reflects the interindividual
      differences of hepatic drug-metabolizing capacity and drug responsiveness. 

PMID- 25385621
TI  - Effects of temperature and precipitation variability on the risk of violence in
      sub-Saharan Africa, 1980-2012.
AB  - Ongoing debates in the academic community and in the public policy arena continue
      without clear resolution about the significance of global climate change for the
      risk of increased conflict. Sub-Saharan Africa is generally agreed to be the
      region most vulnerable to such climate impacts. Using a large database of
      conflict events and detailed climatological data covering the period 1980-2012,
      we apply a multilevel modeling technique that allows for a more nuanced
      understanding of a climate-conflict link than has been seen heretofore. In the
      aggregate, high temperature extremes are associated with more conflict; however,
      different types of conflict and different subregions do not show consistent
      relationship with temperature deviations. Precipitation deviations, both high and
      low, are generally not significant. The location and timing of violence are
      influenced less by climate anomalies (temperature or precipitation variations
      from normal) than by key political, economic, and geographic factors. We find
      important distinctions in the relationship between temperature extremes and
      conflict by using multiple methods of analysis and by exploiting our time-series
      cross-sectional dataset for disaggregated analyses. 

PMID- 25385622
TI  - Unusual role of epilayer-substrate interactions in determining orientational
      relations in van der Waals epitaxy.
AB  - Using selected-area low-energy electron diffraction analysis, we showed strict
      orientational alignment of monolayer hexagonal boron nitride (h-BN) crystallites
      with Cu(100) surface lattices of Cu foil substrates during atmospheric pressure
      chemical vapor deposition. In sharp contrast, the graphene-Cu(100) system is well
      known to assume a wide range of rotations despite graphene's crystallographic
      similarity to h-BN. Our density functional theory calculations uncovered the
      origin of this surprising difference: The crystallite orientation is determined
      during nucleation by interactions between the cluster's edges and the substrate.
      Unlike the weaker B- and N-Cu interactions, strong C-Cu interactions rearrange
      surface Cu atoms, resulting in the aligned geometry not being a distinct minimum
      in total energy. The discovery made in this specific case runs counter to the
      conventional wisdom that strong epilayer-substrate interactions enhance
      orientational alignment in epitaxy and sheds light on the factors that determine
      orientational relation in van der Waals epitaxy of 2D materials. 

PMID- 25385623
TI  - Ocean surface temperature variability: large model-data differences at decadal
      and longer periods.
AB  - The variability of sea surface temperatures (SSTs) at multidecadal and longer
      timescales is poorly constrained, primarily because instrumental records are
      short and proxy records are noisy. Through applying a new noise filtering
      technique to a global network of late Holocene SST proxies, we estimate SST
      variability between annual and millennial timescales. Filtered estimates of SST
      variability obtained from coral, foraminifer, and alkenone records are shown to
      be consistent with one another and with instrumental records in the frequency
      bands at which they overlap. General circulation models, however, simulate SST
      variability that is systematically smaller than instrumental and proxy-based
      estimates. Discrepancies in variability are largest at low latitudes and increase
      with timescale, reaching two orders of magnitude for tropical variability at
      millennial timescales. This result implies major deficiencies in observational
      estimates or model simulations, or both, and has implications for the attribution
      of past variations and prediction of future change. 

PMID- 25385624
TI  - Polyspecific pyrrolysyl-tRNA synthetases from directed evolution.
AB  - Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA(Pyl) have emerged as
      ideal translation components for genetic code innovation. Variants of the enzyme
      facilitate the incorporation >100 noncanonical amino acids (ncAAs) into proteins.
      PylRS variants were previously selected to acylate N(epsilon)-acetyl-Lys (AcK)
      onto tRNA(Pyl). Here, we examine an N(epsilon)-acetyl-lysyl-tRNA synthetase
      (AcKRS), which is polyspecific (i.e., active with a broad range of ncAAs) and 30
      fold more efficient with Phe derivatives than it is with AcK. Structural and
      biochemical data reveal the molecular basis of polyspecificity in AcKRS and in a
      PylRS variant [iodo-phenylalanyl-tRNA synthetase (IFRS)] that displays both
      enhanced activity and substrate promiscuity over a chemical library of 313 ncAAs.
      IFRS, a product of directed evolution, has distinct binding modes for different
      ncAAs. These data indicate that in vivo selections do not produce optimally
      specific tRNA synthetases and suggest that translation fidelity will become an
      increasingly dominant factor in expanding the genetic code far beyond 20 amino
      acids. 

PMID- 25385625
TI  - Long-term effects of marijuana use on the brain.
AB  - Questions surrounding the effects of chronic marijuana use on brain structure
      continue to increase. To date, however, findings remain inconclusive. In this
      comprehensive study that aimed to characterize brain alterations associated with
      chronic marijuana use, we measured gray matter (GM) volume via structural MRI
      across the whole brain by using voxel-based morphology, synchrony among abnormal
      GM regions during resting state via functional connectivity MRI, and white matter
      integrity (i.e., structural connectivity) between the abnormal GM regions via
      diffusion tensor imaging in 48 marijuana users and 62 age- and sex-matched
      nonusing controls. The results showed that compared with controls, marijuana
      users had significantly less bilateral orbitofrontal gyri volume, higher
      functional connectivity in the orbitofrontal cortex (OFC) network, and higher
      structural connectivity in tracts that innervate the OFC (forceps minor) as
      measured by fractional anisotropy (FA). Increased OFC functional connectivity in
      marijuana users was associated with earlier age of onset. Lastly, a quadratic
      trend was observed suggesting that the FA of the forceps minor tract initially
      increased following regular marijuana use but decreased with protracted regular
      use. This pattern may indicate differential effects of initial and chronic
      marijuana use that may reflect complex neuroadaptive processes in response to
      marijuana use. Despite the observed age of onset effects, longitudinal studies
      are needed to determine causality of these effects. 

PMID- 25385626
TI  - DNA topology confers sequence specificity to nonspecific architectural proteins.
AB  - Topological constraints placed on short fragments of DNA change the disorder
      found in chain molecules randomly decorated by nonspecific, architectural
      proteins into tightly organized 3D structures. The bacterial heat-unstable (HU)
      protein builds up, counter to expectations, in greater quantities and at
      particular sites along simulated DNA minicircles and loops. Moreover, the
      placement of HU along loops with the "wild-type" spacing found in the Escherichia
      coli lactose (lac) and galactose (gal) operons precludes access to key
      recognition elements on DNA. The HU protein introduces a unique spatial pathway
      in the DNA upon closure. The many ways in which the protein induces nearly the
      same closed circular configuration point to the statistical advantage of its
      nonspecificity. The rotational settings imposed on DNA by the repressor proteins,
      by contrast, introduce sequential specificity in HU placement, with the
      nonspecific protein accumulating at particular loci on the constrained duplex.
      Thus, an architectural protein with no discernible DNA sequence-recognizing
      features becomes site-specific and potentially assumes a functional role upon
      loop formation. The locations of HU on the closed DNA reflect long-range
      mechanical correlations. The protein responds to DNA shape and deformability-the
      stiff, naturally straight double-helical structure-rather than to the unique
      features of the constituent base pairs. The structures of the simulated loops
      suggest that HU architecture, like nucleosomal architecture, which modulates the
      ability of regulatory proteins to recognize their binding sites in the context of
      chromatin, may influence repressor-operator interactions in the context of the
      bacterial nucleoid.

PMID- 25385628
TI  - Shortwave and longwave radiative contributions to global warming under increasing
      CO2.
AB  - In response to increasing concentrations of atmospheric CO2, high-end general
      circulation models (GCMs) simulate an accumulation of energy at the top of the
      atmosphere not through a reduction in outgoing longwave radiation (OLR)-as one
      might expect from greenhouse gas forcing-but through an enhancement of net
      absorbed solar radiation (ASR). A simple linear radiative feedback framework is
      used to explain this counterintuitive behavior. It is found that the timescale
      over which OLR returns to its initial value after a CO2 perturbation depends
      sensitively on the magnitude of shortwave (SW) feedbacks. If SW feedbacks are
      sufficiently positive, OLR recovers within merely several decades, and any
      subsequent global energy accumulation is because of enhanced ASR only. In the GCM
      mean, this OLR recovery timescale is only 20 y because of robust SW water vapor
      and surface albedo feedbacks. However, a large spread in the net SW feedback
      across models (because of clouds) produces a range of OLR responses; in those few
      models with a weak SW feedback, OLR takes centuries to recover, and energy
      accumulation is dominated by reduced OLR. Observational constraints of radiative
      feedbacks-from satellite radiation and surface temperature data-suggest an OLR
      recovery timescale of decades or less, consistent with the majority of GCMs.
      Altogether, these results suggest that, although greenhouse gas forcing
      predominantly acts to reduce OLR, the resulting global warming is likely caused
      by enhanced ASR.

PMID- 25385627
TI  - Single mutations in sasA enable a simpler DeltacikA gene network architecture
      with equivalent circadian properties.
AB  - The circadian input kinase of the cyanobacterium Synechococcus elongatus PCC 7942
      (CikA) is important both for synchronizing circadian rhythms with external
      environmental cycles and for transferring temporal information between the
      oscillator and the global transcriptional regulator RpaA (regulator of
      phycobilisome-associated A). KOs of cikA result in one of the most severely
      altered but still rhythmic circadian phenotypes observed. We chemically
      mutagenized a cikA-null S. elongatus strain and screened for second-site
      suppressor mutations that could restore normal circadian rhythms. We identified
      two independent mutations in the Synechococcus adaptive sensor A (sasA) gene that
      produce nearly WT rhythms of gene expression, likely because they compensate for
      the loss of CikA on the temporal phosphorylation of RpaA. Additionally, these
      mutations restore the ability to reset the clock after a short dark pulse through
      an output-independent pathway, suggesting that SasA can influence entrainment
      through direct interactions with KaiC, a property previously unattributed to it.
      These experiments question the evolutionary advantage of integrating CikA into
      the cyanobacterial clock, challenge the conventional construct of separable input
      and output pathways, and show how easily the cell can adapt to restore phenotype
      in a severely compromised genetic network. 

PMID- 25385630
TI  - Nonsensory target-dependent organization of piriform cortex.
AB  - The piriform cortex (PCX) is the largest component of the olfactory cortex and is
      hypothesized to be the locus of odor object formation. The distributed odorant
      representation found in PCX contrasts sharply with the topographical
      representation seen in other primary sensory cortices, making it difficult to
      test this view. Recent work in PCX has focused on functional characteristics of
      these distributed afferent and association fiber systems. However, information
      regarding the efferent projections of PCX and how those may be involved in odor
      representation and object recognition has been largely ignored. To investigate
      this aspect of PCX, we have used the efferent pathway from mouse PCX to the
      orbitofrontal cortex (OFC). Using double fluorescent retrograde tracing, we
      identified the output neurons (OPNs) of the PCX that project to two subdivisions
      of the OFC, the agranular insula and the lateral orbitofrontal cortex (AI-OPNs
      and LO-OPNs, respectively). We found that both AI-OPNs and LO-OPNs showed a
      distinct spatial topography within the PCX and fewer than 10% projected to both
      the AI and the LO as judged by double-labeling. These data revealed that the
      efferent component of the PCX may be topographically organized. Further, these
      data suggest a model for functional organization of the PCX in which the OPNs are
      grouped into parallel output circuits that provide olfactory information to
      different higher centers. The distributed afferent input from the olfactory bulb
      and the local PCX association circuits would then ensure a complete olfactory
      representation, pattern recognition capability, and neuroplasticity in each
      efferent circuit. 

PMID- 25385629
TI  - Gill bacteria enable a novel digestive strategy in a wood-feeding mollusk.
AB  - Bacteria play many important roles in animal digestive systems, including the
      provision of enzymes critical to digestion. Typically, complex communities of
      bacteria reside in the gut lumen in direct contact with the ingested materials
      they help to digest. Here, we demonstrate a previously undescribed digestive
      strategy in the wood-eating marine bivalve Bankia setacea, wherein digestive
      bacteria are housed in a location remote from the gut. These bivalves, commonly
      known as shipworms, lack a resident microbiota in the gut compartment where wood
      is digested but harbor endosymbiotic bacteria within specialized cells in their
      gills. We show that this comparatively simple bacterial community produces wood
      degrading enzymes that are selectively translocated from gill to gut. These
      enzymes, which include just a small subset of the predicted wood-degrading
      enzymes encoded in the endosymbiont genomes, accumulate in the gut to the near
      exclusion of other endosymbiont-made proteins. This strategy of remote enzyme
      production provides the shipworm with a mechanism to capture liberated sugars
      from wood without competition from an endogenous gut microbiota. Because only
      those proteins required for wood digestion are translocated to the gut, this
      newly described system reveals which of many possible enzymes and enzyme
      combinations are minimally required for wood degradation. Thus, although it has
      historically had negative impacts on human welfare, the shipworm digestive
      process now has the potential to have a positive impact on industries that
      convert wood and other plant biomass to renewable fuels, fine chemicals, food,
      feeds, textiles, and paper products. 

PMID- 25385631
TI  - Pharmacological protection of retinal pigmented epithelial cells by sulindac
      involves PPAR-alpha.
AB  - The retinal pigmented epithelial (RPE) layer is one of the major ocular tissues
      affected by oxidative stress and is known to play an important role in the
      etiology of age-related macular degeneration (AMD), the major cause of blinding
      in the elderly. In the present study, sulindac, a nonsteroidal antiinflammatory
      drug (NSAID), was tested for protection against oxidative stress-induced damage
      in an established RPE cell line (ARPE-19). Besides its established
      antiinflammatory activity, sulindac has previously been shown to protect cardiac
      tissue against ischemia/reperfusion damage, although the exact mechanism was not
      elucidated. As shown here, sulindac can also protect RPE cells from chemical
      oxidative damage or UV light by initiating a protective mechanism similar to what
      is observed in ischemic preconditioning (IPC) response. The mechanism of
      protection appears to be triggered by reactive oxygen species (ROS) and involves
      known IPC signaling components such as PKG and PKC epsilon in addition to the
      mitochondrial ATP-sensitive K(+) channel. Sulindac induced iNOS and Hsp70, late
      phase IPC markers in the RPE cells. A unique feature of the sulindac protective
      response is that it involves activation of the peroxisome proliferator-activated
      receptor alpha (PPAR-alpha). We have also used low-passage human fetal RPE and
      polarized primary fetal RPE cells to validate the basic observation that sulindac
      can protect retinal cells against oxidative stress. These findings indicate a
      mechanism for preventing oxidative stress in RPE cells and suggest that sulindac
      could be used therapeutically for slowing the progression of AMD. 

PMID- 25385632
TI  - Hidden cycle of dissolved organic carbon in the deep ocean.
AB  - Marine dissolved organic carbon (DOC) is a large (660 Pg C) reactive carbon
      reservoir that mediates the oceanic microbial food web and interacts with climate
      on both short and long timescales. Carbon isotopic content provides information
      on the DOC source via delta(13)C and age via Delta(14)C. Bulk isotope
      measurements suggest a microbially sourced DOC reservoir with two distinct
      components of differing radiocarbon age. However, such measurements cannot
      determine internal dynamics and fluxes. Here we analyze serial oxidation
      experiments to quantify the isotopic diversity of DOC at an oligotrophic site in
      the central Pacific Ocean. Our results show diversity in both stable and radio
      isotopes at all depths, confirming DOC cycling hidden within bulk analyses. We
      confirm the presence of isotopically enriched, modern DOC cocycling with an
      isotopically depleted older fraction in the upper ocean. However, our results
      show that up to 30% of the deep DOC reservoir is modern and supported by a 1 Pg/y
      carbon flux, which is 10 times higher than inferred from bulk isotope
      measurements. Isotopically depleted material turns over at an apparent time scale
      of 30,000 y, which is far slower than indicated by bulk isotope measurements.
      These results are consistent with global DOC measurements and explain both the
      fluctuations in deep DOC concentration and the anomalous radiocarbon values of
      DOC in the Southern Ocean. Collectively these results provide an unprecedented
      view of the ways in which DOC moves through the marine carbon cycle. 

PMID- 25385634
TI  - Gil ashwell, 1916-2014.

PMID- 25385633
TI  - Putative chanzyme activity of TRPM2 cation channel is unrelated to pore gating.
AB  - Transient receptor potential melastatin 2 (TRPM2) is a Ca(2+)-permeable cation
      channel expressed in immune cells of phagocytic lineage, pancreatic beta cells,
      and brain neurons and is activated under oxidative stress. TRPM2 activity is
      required for immune cell activation and insulin secretion and is responsible for
      postischemic neuronal cell death. TRPM2 is opened by binding of ADP ribose (ADPR)
      to its C-terminal cytosolic nudix-type motif 9 (NUDT9)-homology (NUDT9-H) domain,
      which, when expressed in isolation, cleaves ADPR into AMP and ribose-5-phosphate.
      A suggested coupling of this enzymatic activity to channel gating implied a
      potentially irreversible gating cycle, which is a unique feature of a small group
      of channel enzymes known to date. The significance of such a coupling lies in the
      conceptually distinct pharmacologic strategies for modulating the open
      probability of channels obeying equilibrium versus nonequilibrium gating
      mechanisms. Here we examine the potential coupling of TRPM2 enzymatic activity to
      pore gating. Mutation of several residues proposed to enhance or eliminate NUDT9
      H catalytic activity all failed to affect channel gating kinetics. An ADPR
      analog, alpha-beta-methylene-ADPR (AMPCPR), was shown to be entirely resistant to
      hydrolysis by NUDT9, but nevertheless supported TRPM2 channel gating, albeit with
      reduced apparent affinity. The rate of channel deactivation was not slowed but,
      rather, accelerated in AMPCPR. These findings, as well as detailed analyses of
      steady-state gating kinetics of single channels recorded in the presence of a
      range of concentrations of ADPR or AMPCPR, identify TRPM2 as a simple ligand
      gated channel that obeys an equilibrium gating mechanism uncoupled from its
      enzymatic activity. 

PMID- 25385636
TI  - Oncogenic activity of the regulatory subunit p85beta of phosphatidylinositol 3
      kinase (PI3K).
AB  - Expression of the regulatory subunit p85beta of PI3K induces oncogenic
      transformation of primary avian fibroblasts. The transformed cells proliferate at
      an increased rate compared with nontransformed controls and show elevated levels
      of PI3K signaling. The oncogenic activity of p85beta requires an active PI3K-TOR
      signaling cascade and is mediated by the p110alpha and p110beta isoforms of the
      PI3K catalytic subunit. The data suggest that p85beta is a less effective
      inhibitor of the PI3K catalytic subunit than p85alpha and that this reduced level
      of p110 inhibition accounts for the oncogenic activity of p85beta. 

PMID- 25385638
TI  - Hard sphere-like glass transition in eye lens alpha-crystallin solutions.
AB  - We study the equilibrium liquid structure and dynamics of dilute and concentrated
      bovine eye lens alpha-crystallin solutions, using small-angle X-ray scattering,
      static and dynamic light scattering, viscometry, molecular dynamics simulations,
      and mode-coupling theory. We find that a polydisperse Percus-Yevick hard-sphere
      liquid-structure model accurately reproduces both static light scattering data
      and small-angle X-ray scattering liquid structure data from alpha-crystallin
      solutions over an extended range of protein concentrations up to 290 mg/mL or 49%
      vol fraction and up to ca. 330 mg/mL for static light scattering. The measured
      dynamic light scattering and viscosity properties are also consistent with those
      of hard-sphere colloids and show power laws characteristic of an approach toward
      a glass transition at alpha-crystallin volume fractions near 58%. Dynamic light
      scattering at a volume fraction beyond the glass transition indicates formation
      of an arrested state. We further perform event-driven molecular dynamics
      simulations of polydisperse hard-sphere systems and use mode-coupling theory to
      compare the measured dynamic power laws with those of hard-sphere models. The
      static and dynamic data, simulations, and analysis show that aqueous eye lens
      alpha-crystallin solutions exhibit a glass transition at high concentrations that
      is similar to those found in hard-sphere colloidal systems. The alpha-crystallin
      glass transition could have implications for the molecular basis of presbyopia
      and the kinetics of molecular change during cataractogenesis. 

PMID- 25385640
TI  - Surface attachment induces Pseudomonas aeruginosa virulence.
AB  - Pseudomonas aeruginosa infects every type of host that has been examined by
      deploying multiple virulence factors. Previous studies of virulence regulation
      have largely focused on chemical cues, but P. aeruginosa may also respond to
      mechanical cues. Using a rapid imaging-based virulence assay, we demonstrate that
      P. aeruginosa activates virulence in response to attachment to a range of
      chemically distinct surfaces, suggesting that this bacterial species responds to
      mechanical properties of its substrates. Surface-activated virulence requires
      quorum sensing, but activating quorum sensing does not induce virulence without
      surface attachment. The activation of virulence by surfaces also requires the
      surface-exposed protein PilY1, which has a domain homologous to a eukaryotic
      mechanosensor. Specific mutation of the putative PilY1 mechanosensory domain is
      sufficient to induce virulence in non-surface-attached cells, suggesting that
      PilY1 mediates surface mechanotransduction. Triggering virulence only when cells
      are both at high density and attached to a surface-two host-nonspecific cues
      explains how P. aeruginosa precisely regulates virulence while maintaining broad
      host specificity.

PMID- 25385641
TI  - Sample processing obscures cancer-specific alterations in leukemic
      transcriptomes.
AB  - Substantial effort is currently devoted to identifying cancer-associated
      alterations using genomics. Here, we show that standard blood collection
      procedures rapidly change the transcriptional and posttranscriptional landscapes
      of hematopoietic cells, resulting in biased activation of specific biological
      pathways; up-regulation of pseudogenes, antisense RNAs, and unannotated coding
      isoforms; and RNA surveillance inhibition. Affected genes include common
      mutational targets and thousands of other genes participating in processes such
      as chromatin modification, RNA splicing, T- and B-cell activation, and NF-kappaB
      signaling. The majority of published leukemic transcriptomes exhibit signals of
      this incubation-induced dysregulation, explaining up to 40% of differences in
      gene expression and alternative splicing between leukemias and reference normal
      transcriptomes. The effects of sample processing are particularly evident in pan
      cancer analyses. We provide biomarkers that detect prolonged incubation of
      individual samples and show that keeping blood on ice markedly reduces changes to
      the transcriptome. In addition to highlighting the potentially confounding
      effects of technical artifacts in cancer genomics data, our study emphasizes the
      need to survey the diversity of normal as well as neoplastic cells when
      characterizing tumors. 

PMID- 25385643
TI  - XerD-mediated FtsK-independent integration of TLCphi into the Vibrio cholerae
      genome.
AB  - As in most bacteria, topological problems arising from the circularity of the two
      Vibrio cholerae chromosomes, chrI and chrII, are resolved by the addition of a
      crossover at a specific site of each chromosome, dif, by two tyrosine
      recombinases, XerC and XerD. The reaction is under the control of a cell division
      protein, FtsK, which activates the formation of a Holliday Junction (HJ)
      intermediate by XerD catalysis that is resolved into product by XerC catalysis.
      Many plasmids and phages exploit Xer recombination for dimer resolution and for
      integration, respectively. In all cases so far described, they rely on an
      alternative recombination pathway in which XerC catalyzes the formation of a HJ
      independently of FtsK. This is notably the case for CTXphi, the cholera toxin
      phage. Here, we show that in contrast, integration of TLCphi, a toxin-linked
      cryptic satellite phage that is almost always found integrated at the chrI dif
      site before CTXphi, depends on the formation of a HJ by XerD catalysis, which is
      then resolved by XerC catalysis. The reaction nevertheless escapes the normal
      cellular control exerted by FtsK on XerD. In addition, we show that the same
      reaction promotes the excision of TLCphi, along with any CTXphi copy present
      between dif and its left attachment site, providing a plausible mechanism for how
      chrI CTXphi copies can be eliminated, as occurred in the second wave of the
      current cholera pandemic. 

PMID- 25385645
TI  - Intravital imaging reveals distinct responses of depleting dynamic tumor
      associated macrophage and dendritic cell subpopulations.
AB  - Tumor-infiltrating inflammatory cells comprise a major part of the stromal
      microenvironment and support cancer progression by multiple mechanisms. High
      numbers of tumor myeloid cells correlate with poor prognosis in breast cancer and
      are coupled with the angiogenic switch and malignant progression. However, the
      specific roles and regulation of heterogeneous tumor myeloid populations are
      incompletely understood. CSF-1 is a major myeloid cell mitogen, and signaling
      through its receptor CSF-1R is also linked to poor outcomes. To characterize
      myeloid cell function in tumors, we combined confocal intravital microscopy with
      depletion of CSF-1R-dependent cells using a neutralizing CSF-1R antibody in the
      mouse mammary tumor virus long-terminal region-driven polyoma middle T antigen
      breast cancer model. The depleted cells shared markers of tumor-associated
      macrophages and dendritic cells (M-DCs), matching the phenotype of tumor
      dendritic cells that take up antigens and interact with T cells. We defined
      functional subgroups within the M-DC population by imaging endocytic and matrix
      metalloproteinase activity. Anti-CSF-1R treatment altered stromal dynamics and
      impaired both survival of M-DCs and accumulation of new M-DCs, but did not
      deplete Gr-1(+) neutrophils or block doxorubicin-induced myeloid cell
      recruitment, and had a minimal effect on lung myeloid cells. Nevertheless,
      prolonged treatment led to delayed tumor growth, reduced vascularity, and
      decreased lung metastasis. Because the myeloid infiltrate in metastatic lungs
      differed significantly from that in mammary tumors, the reduction in metastasis
      may result from the impact on primary tumors. The combination of functional
      analysis by intravital imaging with cellular characterization has refined our
      understanding of the effects of experimental targeted therapies on the tumor
      microenvironment. 

PMID- 25385646
TI  - mTOR kinase inhibitors promote antibody class switching via mTORC2 inhibition.
AB  - The mammalian target of rapamycin (mTOR) is a kinase that functions in two
      distinct complexes, mTORC1 and mTORC2. In peripheral B cells, complete deletion
      of mTOR suppresses germinal center B-cell responses, including class switching
      and somatic hypermutation. The allosteric mTORC1 inhibitor rapamycin blocks
      proliferation and differentiation, but lower doses can promote protective IgM
      responses. To elucidate the complexity of mTOR signaling in B cells further, we
      used ATP-competitive mTOR kinase inhibitors (TOR-KIs), which inhibit both mTORC1
      and mTORC2. Although TOR-KIs are in clinical development for cancer, their
      effects on mature lymphocytes are largely unknown. We show that high
      concentrations of TOR-KIs suppress B-cell proliferation and differentiation, yet
      lower concentrations that preserve proliferation increase the fraction of B cells
      undergoing class switching in vitro. Transient treatment of mice with the TOR-KI
      compound AZD8055 increased titers of class-switched high-affinity antibodies to a
      hapten-protein conjugate. Mechanistic investigation identified opposing roles for
      mTORC1 and mTORC2 in B-cell differentiation and showed that TOR-KIs enhance class
      switching in a manner dependent on forkhead box, subgroup O (FoxO) transcription
      factors. These observations emphasize the distinct actions of TOR-KIs compared
      with rapamycin and suggest that TOR-KIs might be useful to enhance production of
      class-switched antibodies following vaccination. 

PMID- 25385647
TI  - Mapping of long-range INS promoter interactions reveals a role for calcium
      activated chloride channel ANO1 in insulin secretion.
AB  - We used circular chromatin conformation capture (4C) to identify a physical
      contact in human pancreatic islets between the region near the insulin (INS)
      promoter and the ANO1 gene, lying 68 Mb away on human chromosome 11, which
      encodes a Ca(2+)-dependent chloride ion channel. In response to glucose, this
      contact was strengthened and ANO1 expression increased, whereas inhibition of INS
      gene transcription by INS promoter targeting siRNA decreased ANO1 expression,
      revealing a regulatory effect of INS promoter on ANO1 expression. Knockdown of
      ANO1 expression caused decreased insulin secretion in human islets, establishing
      a physical proximity-dependent feedback loop involving INS transcription, ANO1
      expression, and insulin secretion. To explore a possible role of ANO1 in insulin
      metabolism, we carried out experiments in Ano1(+/-) mice. We observed reduced
      serum insulin levels and insulin-to-glucose ratios in high-fat diet-fed Ano1(+/-)
      mice relative to Ano1(+/+) mice fed the same diet. Our results show that
      determination of long-range contacts within the nucleus can be used to detect
      novel and physiologically relevant mechanisms. They also show that networks of
      long-range physical contacts are important to the regulation of insulin
      metabolism. 

PMID- 25385648
TI  - Methane emissions from Alaska in 2012 from CARVE airborne observations.
AB  - We determined methane (CH4) emissions from Alaska using airborne measurements
      from the Carbon Arctic Reservoirs Vulnerability Experiment (CARVE). Atmospheric
      sampling was conducted between May and September 2012 and analyzed using a
      customized version of the polar weather research and forecast model linked to a
      Lagrangian particle dispersion model (stochastic time-inverted Lagrangian
      transport model). We estimated growing season CH4 fluxes of 8 +/- 2 mg CH4?m(
      2)?d(-1) averaged over all of Alaska, corresponding to fluxes from wetlands of
      56(-13)(+22) mg CH4?m(-2)?d(-1) if we assumed that wetlands are the only source
      from the land surface (all uncertainties are 95% confidence intervals from a
      bootstrapping analysis). Fluxes roughly doubled from May to July, then decreased
      gradually in August and September. Integrated emissions totaled 2.1 +/- 0.5 Tg
      CH4 for Alaska from May to September 2012, close to the average (2.3; a range of
      0.7 to 6 Tg CH4) predicted by various land surface models and inversion analyses
      for the growing season. Methane emissions from boreal Alaska were larger than
      from the North Slope; the monthly regional flux estimates showed no evidence of
      enhanced emissions during early spring or late fall, although these bursts may be
      more localized in time and space than can be detected by our analysis. These
      results provide an important baseline to which future studies can be compared.

PMID- 25385649
TI  - Reply to Metson et al.: The importance of phosphorus perturbations.

PMID- 25385650
TI  - Phosphorus is a key component of the resource demands for meat, eggs, and dairy
      production in the United States.

PMID- 25385651
TI  - Reply to Skoyles: Decline in growth rate, not muscle mass, predicts the human
      childhood peak in brain metabolism.

PMID- 25385652
TI  - Skeletal muscle-induced hypoglycemia risk, not life history energy trade-off,
      links high child brain glucose use to slow body growth.

PMID- 25385653
TI  - Refractory migraine in a "just world".
AB  - The "just world hypothesis" is the belief that a poor outcome to treatment always
      implies patient noncompliance. However, all disease states have a spectrum of
      severity, with the most severe end representing treatment failures despite
      compliant patients and excellent care. Some refractory headache patients
      represent this group of compliant patients, who had excellent care but who have
      bad disease. 

PMID- 25385654
TI  - Absence and size of massa intermedia in patients with schizophrenia and bipolar
      disorder.
AB  - OBJECTIVE: To evaluate the absence and size of massa intermedia (MI), a midline
      thalamic structure, and its gender-specific alteration in patients with
      schizophrenia and bipolar disorder. METHODS: Thirty-five patients with
      schizophrenia (17 females and 18 males), 21 patients with bipolar disorder (15
      females and 6 males) and 89 healthy controls (50 females and 39 males) were
      evaluated by magnetic resonance imaging. Thin-slice magnetic resonance images of
      the brain were evaluated. MI was determined in coronal and sagittal images, and
      area of the MI was measured on the sagittal plane. RESULTS: Females had a
      significantly lower incidence of absent MI compared with males in the healthy
      control group. The absence of MI in schizophrenia and bipolar patients was not
      higher than the incidence in healthy controls. The size of MI showed a gender
      difference. The mean MI area size was smaller in female schizophrenia patients
      than in female controls, while no significant difference was observed between
      male schizophrenia patients and their controls. CONCLUSIONS: The size of MI, a
      gender difference midline structure, is smaller in females with schizophrenia,
      and the results of this study support other studies of structural aberration of
      the thalamus and other midline structures in the brains of patients with
      schizophrenia.

PMID- 25385655
TI  - The response to sulpiride in major depression before and after cognitive
      behavioural therapy: D2 receptor function.
AB  - BACKGROUND: Previous studies have suggested that antidepressant treatment of
      depression may potentiate dopamine transmission through increased sensitivity of
      postsynaptic D2 receptors. METHOD: D2 receptor function was assessed in 24
      patients with major depression before and 16 patients after 16 weeks of treatment
      with cognitive behavioural therapy (CBT) using a challenge with a selective D2
      antagonist, sulpiride. Four hundred milligrams of sulpiride was administered
      orally on two test days and response was measured by the change in prolactin
      levels and changes in self-rating scale measures of mood, anxiety and pleasure.
      RESULTS: The prolactin response to sulpiride (as measured by the maximum
      prolactin level) was significantly increased after CBT (z = -2.792, p = 0.005).
      Sulpiride resulted in an improvement on mood ratings on both test days, but after
      CBT, this effect was significantly diminished as measured by the Profile of Mood
      States score (t = -2.27, p = 0.038). CONCLUSIONS: After 16 weeks of CBT, we
      detected an enhanced prolactin response to sulpiride, suggesting an increased
      sensitivity of D2 receptor functioning.

PMID- 25385656
TI  - Attention profiles in autistic children with and without comorbid hyperactivity
      and attention problems.
AB  - OBJECTIVE: Psychopathological, neuropsychological and genetic findings indicate
      an association between ASD Spectrum Disorder (ASD) and attention
      deficit/hyperactivity disorder (ADHD). The goal of this study was to compare the
      neuropsychological profiles of attention functions in children with ADHD and with
      ASD and without comorbid ADHD. The hypothesis was that either ADHD and autistic
      children with comorbid ADHD symptoms were more impaired in inhibition and
      sustained attention performance and that all individuals with ASD show more
      deficits in divided attention. METHOD: Children aged 6 to 18 years old with ADHD
      (n = 30) or ASD with (n = 21) and without comorbid ADHD (n = 20) and 30 healthy
      children were included consecutively. Psychopathology was evaluated using the
      KIDDIE-SADS and symptom checklists for ADHD and ASD according to DSM-IV. Assessed
      neuropsychological functioning included inhibition, sustained as well as divided
      attention and alertness tasks. RESULTS: Age and IQ-corrected z-scores were used.
      Statistically significant group effects were found for the variables sustained
      attention median (F = 3.2, = .02), hits (F = 3.3, p = .02) and false alarms (F =
      3.9, p = .01), divided attention hits (F = 3.3, p = .02), errors (F = 3.1, p =
      .03) and false alarms (F = 3.3, p = .03) and alertness false alarms (F = 2.9, p =
      .04). Pearson Correlations revealed associations between ADHD symptoms and
      sustained attention in the ADHD group and between ADHD symptoms and inhibition in
      the ASD+ group. CONCLUSION: Our hypothesis was partly confirmed as ADHD children
      showed more deficits in sustained attention and ASD children in divided attention
      tasks. However there was no evidence that children with ASD and comorbid ADHD
      symptoms have a specific profile in comparison to pure ASD children.

PMID- 25385657
TI  - Black phosphorus nanoelectromechanical resonators vibrating at very high
      frequencies.
AB  - We report on the experimental demonstration of a new type of
      nanoelectromechanical resonator based on black phosphorus crystals. Facilitated
      by a highly efficient dry transfer technique, crystalline black phosphorus flakes
      are harnessed to enable drumhead resonators vibrating at high and very high
      frequencies (HF and VHF bands, up to ~100 MHz). We investigate the resonant
      vibrational responses from the black phosphorus crystals by devising both
      electrical and optical excitation schemes, in addition to measuring the undriven
      thermomechanical motions in these suspended nanostructures. Flakes with
      thicknesses from ~200 nm down to ~20 nm clearly exhibit elastic characteristics
      transitioning from the plate to the membrane regime. Both frequency- and time
      domain measurements of the nanomechanical resonances show that very thin black
      phosphorus crystals hold interesting potential for moveable and vibratory devices
      and for semiconductor transducers where high-speed mechanical motions could be
      coupled to the attractive electronic and optoelectronic properties of black
      phosphorus. 

PMID- 25385658
TI  - Subretinal injection of amyloid-beta peptide accelerates RPE cell senescence and
      retinal degeneration.
AB  - Drusen are considered a hallmark characteristic of age-related macular
      degeneration (AMD). In our previous study, we found that amyloid-beta (Abeta)
      peptide, a component of drusen, induced the cells of the retinal pigment
      epithelium (RPE; RPE cells) to enter senescence; however, its effects in vivo
      remain unknown. Thus, the present study was carried out to explore the in vivo
      effects of Abeta peptide on RPE cell senescence and senescence-associated
      inflammation in C57BL/6 mice. C57BL/6 mice received a subretinal injection of
      Abeta(1-42) peptide; on day 7 post-injection, the mice were anesthetized and
      subjected to whole-body perfusion with 4% paraformaldehyde (PFA) in PBS and the
      whole eyes were then enucleated. Retinal function was assessed by
      electroretinography (ERG), and the morphological characteristics of the retina
      were examined by light and electron microscopy. Fundus autofluorescence (FAF) was
      examined by confocal scanning laser ophthalmoscopy (cSLO). The expression of
      p16INK4a, a marker of cellular senescence, was examined by immunofluorescence
      staining and western blot analysis. The RPE-choroid was analyzed for cytokine
      expression by RT-PCR. In Abeta(1-42)-injected mice, scotopic ERG responses
      declined. Degenerative alterations, including the disruption of the inner segment
      (IS)/outer segment (OS) junction and extensive vacuolation and thickness of
      Bruch's membrane (BrM) were observed under a a light microscope. The accumulation
      of vacuoles and the loss of basal infoldings in the RPE were identified using an
      electron microscope. FAF and p16INK4a expression increased in Abeta(1-42)
      injected mice. In addition, Abeta(1-42) upregulated interleukin (IL)-6 and IL-8
      gene expression in the RPE-choroid. In conclusion, our results confirm the
      effects of Abeta(1-42) peptide on RPE senescence in vivo. The Abeta-injected mice
      developed AMD-like ocular pathology. It is thus suggested that RPE cell
      senescence is a potential mechanistic link between inflammation and retinal
      degeneration.

PMID- 25385659
TI  - Immobilization of halophilic Bacillus sp. EMB9 protease on functionalized silica
      nanoparticles and application in whey protein hydrolysis.
AB  - The present work targets the fabrication of an active, stable, reusable enzyme
      preparation using functionalized silica nanoparticles as an effective enzyme
      support for crude halophilic Bacillus sp. EMB9 protease. The immobilization
      efficiency under optimized conditions was 60%. Characterization of the
      immobilized preparation revealed marked increase in pH and thermal stability. It
      retained 80% of its original activity at 70  degrees C while t 1/2 at 50  degrees
      C showed a five-fold enhancement over that for the free protease. Kinetic
      constants K m and V max were indicative of a higher reaction velocity along with
      decreased affinity for substrate. The preparation could be efficiently reused up
      to 6 times and successfully hydrolysed whey proteins with high degree of
      hydrolysis. Immobilization of a crude halophilic protease on a nanobased scaffold
      makes the process cost effective and simple.

PMID- 25385660
TI  - Exposure to prenatal smoking and early-life body composition: the healthy start
      study.
AB  - OBJECTIVES: To examine associations between exposure to prenatal smoking and
      early-life changes in fat mass (FM), fat-free mass (FFM), and anthropometrics.
      METHODS: About 670 mother-offspring pairs were analyzed in the longitudinal
      Healthy Start study. Maternal smoking data were collected during prenatal
      research visits. Offspring body composition and size were measured by air
      displacement plethysmography at delivery and postnatal follow-up (5 months)
      visits. RESULTS: Comparing exposed and unexposed offspring, exposure to prenatal
      smoking was significantly associated with reduced neonatal FM (P = 0.007) and FFM
      (P = 0.02). In contrast, at 5 months, exposed offspring had comparable FM (P =
      0.61) and FFM (P = 0.41). After subsequent adjustment for birth weight, offspring
      exposed to prenatal smoking had significantly greater FFM (154.7 g, 0.5, 309.0; P
      = 0.049) and sum of skinfolds (2.7 mm, 0.06, 5.3; P = 0.04). From delivery to
      follow-up, exposed offspring had significantly greater increases in FFM (156.4 g,
      2.8, 310.1; P = 0.046) and sum of skinfolds (2.7 mm, 0.06, 5.3; P = 0.04), even
      after adjustment for respective delivery measures. CONCLUSIONS: Exposure to
      prenatal smoking was significantly associated with rapid postnatal growth, which
      may increase the offspring's risk of metabolic diseases.

PMID- 25385661
TI  - An insight into the key genes and biological functions associated with insulin
      resistance in adipose tissue with microarray technology.
AB  - In the present study, the key genes and biological functions associated with
      insulin resistance were investigated by comparing the gene expression profiles of
      adipose tissue obtained from insulin-sensitive and insulin-resistant patients.
      The gene expression data set GSE20950 was downloaded from the Gene Expression
      Omnibus, including 39 adipose tissue samples obtained from insulin-sensitive and
      insulin-resistant patients undergoing gastric bypass surgery. Adipose samples
      were divided into two groups (the insulin-sensitive and insulin-resistant groups)
      and the differentially expressed genes (DEGs) were screened out with packages of
      R. The interactions among DEGs were retrieved with Osprey and functional
      enrichment analysis was performed with the WebGestalt system. Information
      regarding the interaction network and enriched biological functions was combined
      to construct a functional interaction network. Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway analysis was then conducted using the Database for
      Annotation, Visualization and Integrated Discovery. A total of 170 DEGs were
      detected in the insulin-sensitive group, 8 downregulated and 162 upregulated.
      Response to glucose stimulus was the most significantly over-represented
      functional term. The focal adhesion pathway was identified to be significant in
      the genes of the functional interaction network. The present study revealed key
      biological functions and DEGs in adipose tissues associated with insulin
      resistance, which may facilitate the development of novel therapies for insulin
      resistance and diabetes.

PMID- 25385662
TI  - Dutch evidence statement for pelvic physical therapy in patients with anal
      incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: To promote agreement among and support the quality
      of pelvic physiotherapists' skills and clinical reasoning in The Netherlands, an
      Evidence Statement Anal Incontinence (AI) was developed based on the practice
      driven problem definitions outlined. We present a summary of the current state of
      knowledge and formulate recommendations for a methodical assessment and treatment
      for patients with AI, and place the evidence in a broader perspective of current
      developments. METHODS: Electronic literature searches were conducted in relevant
      databases with regard to prevalence, incidence, costs, etiological and prognostic
      factors, predictors of response to therapy, prevention, assessment, and
      treatment. The recommendations have been formulated on the basis of scientific
      evidence and where no evidence was available, recommendations were consensus
      based. RESULTS: The evidence statement incorporates a practice statement with
      corresponding notes that clarify the recommendations, and accompanying
      flowcharts, describing the steps and recommendations with regard to the
      diagnostic and therapeutic process. The diagnostic process consists of history
      taking and physical examination supported by measurement instruments. For each
      problem category for patients with AI, a certain treatment plan can be
      distinguished dependent on the presence of pelvic floor dysfunction, awareness of
      loss of stools, comorbidity, neurological problems, adequate anorectal sensation,
      and (in)voluntary control. Available evidence and expert opinion support the use
      of education, pelvic floor muscle training, biofeedback, and electrostimulation
      in selected patients. CONCLUSIONS: The evidence statement reflects the current
      state of knowledge for a methodical and systematic physical therapeutic
      assessment and treatment for patients with AI.

PMID- 25385663
TI  - Genes affecting warfarin response-interactive or additive?
AB  - Genotypes for cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase complex 1
      (VKORC1) contribute significantly to the inter-patient variability in warfarin
      dose requirements. These genotypes in addition to clinical factors explain
      approximately 50% of the dose variability in Europeans, but less in other
      populations. Thus, a large portion of the variability remains unexplained and has
      been the focus of on-going research. Trials evaluating the clinical utility of
      genotype-guided warfarin dosing have shown a benefit in Europeans, but not in an
      ethnically diverse cohort. Identifying and accounting for variants important in
      non-European populations will likely be necessary before a benefit with genotype
      guided dosing will be realized in these populations.

PMID- 25385664
TI  - Influenza-associated bacterial pneumonia; managing and controlling infection on
      two fronts.
AB  - Bacterial pneumonia complicating influenza is well-recognized as a severe
      manifestation of influenza, accounting for a substantial number of deaths from
      the 1918 influenza pandemic. Influenza-associated bacterial pneumonia remains a
      major contributor to the burden of influenza, and poses new challenges as
      antibiotic-resistant organisms such as methicillin-resistant Staphylococcus
      aureus spread. We provide an overview of the current state of knowledge of the
      epidemiology and co-pathogenesis of influenza-associated bacterial pneumonia, and
      outline management approaches and their limitations. We review preventative
      measures and discuss implications for pandemic planning. Knowledge gaps are
      underscored and future research directions are proposed. 

PMID- 25385665
TI  - Nitrous oxide procedural sedation in non-fasting pediatric patients undergoing
      minor surgery: a 12-year experience with 1,058 patients.
AB  - BACKGROUND: Nitrous oxide's safety and efficacy for minor procedures is an
      alternative to general anesthesia, complex sedation protocols, or local
      anesthetic alone. METHODS: A retrospective review of prospectively-collected data
      (2000-2012) identified 1,058 children who received single-agent nitrous oxide for
      minor surgery. RESULTS: Children (n = 1,058, male 42 %, female 58 %) aged 1-23
      years (mean = 9.8 + 5.1 years) were identified. Only nine children (0.9 %)
      fasted. ASA status was I-II in 1,053 (99.5 %) of patients; five (0.5 %) had an
      ASA III. There were no major complications (desaturation, emergency admission,
      apnea, airway obstruction, bradycardia) or aborted procedures. Minor
      complications occurred in 1.8 %; there was no association between these
      complications and ASA, fasting status or maximum nitrous oxide percentage
      administered (all p > 0.05). Post-operatively, 98 % of patients denied getting an
      injection. Eighty-two percent reported mild or no procedural pain. CONCLUSION:
      This is the longest reported study using non-anesthesiologist-administered
      nitrous oxide as a single-agent for minor surgical procedures. The technique
      provides safe sedation and excellent amnesia, allowing pain and anxiety-reduced
      surgery with no fasting or postoperative monitoring.

PMID- 25385667
TI  - Reply to the letter from Canpolat and colleagues.

PMID- 25385666
TI  - Liver injury attenuation by curcumin in a rat NASH model: an Nrf2 activation
      mediated effect?
AB  - AIM: Nuclear factor-erythroid 2-related factor-2 (Nrf2) acts as a defense system
      in the development of nonalcoholic steatohepatitis (NASH). Curcumin is a phenolic
      compound with lipid regulatory, anti-oxidative, anti-inflammatory and anti
      tumorigenic properties that is beneficial in defending against NASH and was
      recently proved to be an Nrf2 activator. The aim of this study was to evaluate
      whether Nrf2 activation could be involved in NASH mitigation by curcumin.
      METHODS: Hepatic, metabolic, and inflammatory parameters, along with hepatic Nrf2
      protein expression were explored in adult Sprague-Dawley rats developing high-fat
      diet-induced NASH and submitted to curcumin gavage for 6 weeks. RESULTS: Curcumin
      administration led to lower degrees of hepatic steatosis and inflammation; lower
      levels of serum aminotransferases, lipids, and homeostasis model assessment of
      insulin resistance; and lower serum and hepatic contents of tumor necrosis factor
      alpha (TNF-alpha), interleukin-6, and malondialdehyde. In contrast, higher
      hepatic contents of glutathione, heme oxygenase-1 and superoxide dismutase were
      observed in rats with curcumin. Moreover, Nrf2 expression in liver cell nuclei
      was significantly higher in rats with curcumin. CONCLUSIONS: Curcumin can prevent
      and ameliorate NASH via lipid reduction, improve insulin resistance, improve anti
      inflammatory, and have antioxidant effects, possibly related to its activation of
      Nrf2.

PMID- 25385668
TI  - Climate change and dead zones.
AB  - Estuaries and coastal seas provide valuable ecosystem services but are
      particularly vulnerable to the co-occurring threats of climate change and oxygen
      depleted dead zones. We analyzed the severity of climate change predicted for
      existing dead zones, and found that 94% of dead zones are in regions that will
      experience at least a 2  degrees C temperature increase by the end of the
      century. We then reviewed how climate change will exacerbate hypoxic conditions
      through oceanographic, ecological, and physiological processes. We found evidence
      that suggests numerous climate variables including temperature, ocean
      acidification, sea-level rise, precipitation, wind, and storm patterns will
      affect dead zones, and that each of those factors has the potential to act
      through multiple pathways on both oxygen availability and ecological responses to
      hypoxia. Given the variety and strength of the mechanisms by which climate change
      exacerbates hypoxia, and the rates at which climate is changing, we posit that
      climate change variables are contributing to the dead zone epidemic by acting
      synergistically with one another and with recognized anthropogenic triggers of
      hypoxia including eutrophication. This suggests that a multidisciplinary,
      integrated approach that considers the full range of climate variables is needed
      to track and potentially reverse the spread of dead zones. 

PMID- 25385670
TI  - Graphical programming interface: A development environment for MRI methods.
AB  - PURPOSE: To introduce a multiplatform, Python language-based, development
      environment called graphical programming interface for prototyping MRI
      techniques. METHODS: The interface allows developers to interact with their
      scientific algorithm prototypes visually in an event-driven environment making
      tasks such as parameterization, algorithm testing, data manipulation, and
      visualization an integrated part of the work-flow. Algorithm developers extend
      the built-in functionality through simple code interfaces designed to facilitate
      rapid implementation. RESULTS: This article shows several examples of algorithms
      developed in graphical programming interface including the non-Cartesian MR
      reconstruction algorithms for PROPELLER and spiral as well as spin simulation and
      trajectory visualization of a FLORET example. CONCLUSION: The graphical
      programming interface framework is shown to be a versatile prototyping
      environment for developing numeric algorithms used in the latest MR techniques.

PMID- 25385669
TI  - Patients' administration preferences: progesterone vaginal insert (Endometrin(r))
      compared to intramuscular progesterone for Luteal phase support.
AB  - BACKGROUND: Administration of exogenous progesterone for luteal phase support has
      become a standard of practice. Intramuscular (IM) injections of progesterone in
      oil (PIO) and vaginal administration of progesterone are the primary routes of
      administration. This report describes the administration preferences expressed by
      women with infertility that were given progesterone vaginal insert (PVI) or
      progesterone in oil injections (PIO) for luteal phase support during fresh IVF
      cycles. METHODS: A questionnaire to assess the tolerability, convenience, and
      ease of administration of PVI and PIO given for luteal phase support was
      completed by infertile women diagnosed with PCOS and planning to undergo IVF. The
      women participated in an open-label study of highly purified human menopausal
      gonadotropins (HP-hMG) compared with recombinant FSH (rFSH) given for stimulation
      of ovulation. RESULTS: Most women commented on the convenience and ease of
      administration of PVI, while a majority of women who administered IM PIO
      described experiencing pain. In addition, their partners often indicated that
      they had experienced at least some anxiety regarding the administration of PIO.
      The most distinguishing difference between PVI and PIO in this study was the
      overall patient preference for PVI. Despite the need to administer PVI either
      twice a day or three times a day, 82.6% of the patients in the PVI group found it
      "very" or "somewhat convenient" compared with 44.9% of women in the PIO group.
      CONCLUSIONS: The results of this comprehensive, prospective patient survey, along
      with findings from other similar reports, suggest that PVI provides an easy-to
      use and convenient method for providing the necessary luteal phase support for
      IVF cycles without the pain and inconvenience of daily IM PIO. Moreover, ongoing
      pregnancy rates with the well-tolerated PVI were as good as the pregnancy rates
      with PIO. TRIAL REGISTRATION: ClinicalTrial.gov, NCT00805935.

PMID- 25385671
TI  - Cleavage of an aryl carbon-nitrogen bond of a phosphazido iron(II) complex
      promoted by hydride metathesis.
AB  - Upon reaction with KBEt3H, the pseudo tetrahedral Fe(II) complex with a bulky
      enamido-phosphazide ligand set undergoes elimination of N2 and 1,3-Me2C6H4 to
      generate the dinuclear Fe(II) derivative with bridging phosphinimido units. When
      the reaction is performed using KBEt3D, no deuterium is incorporated into the
      eliminated 1,3-Me2C6H4; all of the deuterium ends up as D2. When the reaction is
      performed in THF-d8, only 2-d-1,3-Me2C6H3D was detected by GCMS. These studies
      are consistent with a radical mechanism.

PMID- 25385672
TI  - Protrusion force microscopy reveals oscillatory force generation and
      mechanosensing activity of human macrophage podosomes.
AB  - Podosomes are adhesion structures formed in monocyte-derived cells. They are F
      actin-rich columns perpendicular to the substrate surrounded by a ring of
      integrins. Here, to measure podosome protrusive forces, we designed an innovative
      experimental setup named protrusion force microscopy (PFM), which consists in
      measuring by atomic force microscopy the deformation induced by living cells onto
      a compliant Formvar sheet. By quantifying the heights of protrusions made by
      podosomes onto Formvar sheets, we estimate that a single podosome generates a
      protrusion force that increases with the stiffness of the substratum, which is a
      hallmark of mechanosensing activity. We show that the protrusive force generated
      at podosomes oscillates with a constant period and requires combined actomyosin
      contraction and actin polymerization. Finally, we elaborate a model to explain
      the mechanical and oscillatory activities of podosomes. Thus, PFM shows that
      podosomes are mechanosensing cell structures exerting a protrusive force. 

PMID- 25385673
TI  - Droplet nucleation on a well-defined hydrophilic-hydrophobic surface of 10 nm
      order resolution.
AB  - Water condensation on a hybrid hydrophilic-hydrophobic surface was investigated
      to reveal nucleation mechanisms at the microscale. Focused ion beam (FIB)
      irradiation was used to change the wettability of the hydrophobic surface with 10
      nm order spatial resolution. Condensation experiments were conducted using
      environmental scanning electron microscopy; droplets, with a minimum diameter of
      800 nm, lined up on the FIB-irradiated hydrophilic lines. The heterogeneous
      nucleation theory was extended to consider the water molecules attracted to the
      hydrophilic area, thereby enabling explanation of the nucleation mechanism under
      unsaturated conditions. Our results showed that the effective surface coverage of
      the water molecules on the hydrophilic region was 0.1-1.1 at 0.0  degrees C and
      560 Pa and was dependent on the width of the FIB-irradiated hydrophilic lines and
      hydrophobic area. The droplet nucleation mechanism unveiled in this work would
      enable the design of new surfaces with enhanced dropwise condensation heat
      transfer. 

PMID- 25385674
TI  - A lateral ridge augmentation study to evaluate a synthetic membrane for guided
      bone regeneration: an experiment in the canine mandible.
AB  - OBJECTIVES: To evaluate guided bone regeneration outcomes in defects protected
      with an in situ formed polyethylene glycol (PEG) hydrogel membrane as compared to
      a non-cross-linked collagen membrane (CM). MATERIAL AND METHODS: Four mandibular
      alveolar ridge defects were created in eight hound dogs. Regenerative procedures
      were randomly allocated to one of four groups consisting of freeze-dried bone
      allograft, which is referred to in this study as freeze-dried bone xenograft
      (FDBX) + PEG, autogenous bone (AB) + PEG, AB + CM, and AB alone. After 8 weeks,
      titanium dental implants were placed into augmented sites. After 8 weeks of
      allowed time for osseointegration, the animals were sacrificed to harvest block
      specimens for bone-to-implant contact (BIC) and ridge width histomorphometric
      analysis. RESULTS: Polyethylene glycol membranes had an exposure rate of 50% as
      compared to 12.5% for sites grafted with CM. Regenerative outcomes with respect
      to implant placement were least favorable for FDBX + PEG which had implants
      placed in 37.5% of augmented sites compared to 100% implant placement for all
      other groups. No statistically significant differences were noted between groups
      for ridge width measurements in implant and non-implant histologic sections (P >
      0.05). Buccal BIC (%) values between treatment groups also failed to reach
      statistical significant difference (FDBX + PEG [60.2 +/- 9.4]; AB + PEG [58.8 +/-
      8.5]; AB + CM [57.9 +/- 12.8]; AB [61.0 +/- 10.2]). CONCLUSION: When used in
      conjunction with FDBX, PEG had unpredictable bone formation and in most cases
      negatively impacted future implant placement.

PMID- 25385675
TI  - Retinitis pigmentosa caused by mutations in the ciliary MAK gene is relatively
      mild and is not associated with apparent extra-ocular features.
AB  - PURPOSE: Defects in MAK, encoding a protein localized to the photoreceptor
      connecting cilium, have recently been associated with autosomal recessive
      retinitis pigmentosa (RP). The aim of this study is to describe our detailed
      clinical observations in patients with MAK-associated RP, including an assessment
      of syndromic symptoms frequently observed in ciliopathies. METHODS: In this
      international collaborative study, 11 patients carrying nonsense or missense
      mutations in MAK were clinically evaluated, including extensive assessment of the
      medical history, slit-lamp biomicroscopy, ophthalmoscopy, kinetic perimetry,
      electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT),
      autofluorescence imaging and fundus photography. Additionally, we used a
      questionnaire to evaluate the presence of syndromic features and tested the
      olfactory function. RESULTS: MAK-associated RP is not associated with syndromic
      features, not even with subclinical dysfunction of the olfactory apparatus. All
      patients experienced typical RP symptoms of night blindness followed by visual
      field constriction. Symptoms initiated between childhood and the age of 43 (mean:
      23 years). Although some patients experienced vision loss, the visual acuity
      remained normal in most patients. ERG and ophthalmoscopy revealed classic RP
      characteristics, and SD-OCT demonstrated thinning of the overall retina, outer
      nuclear layer and photoreceptor-pigment epithelium complex. CONCLUSION: Nonsense
      and missense mutations in MAK give rise to a non-syndromic recessive RP phenotype
      without apparent extra-ocular features. When compared to other retinal
      ciliopathies, MAK-associated RP appears to be relatively mild and shows
      remarkable resemblance to RP1-associated RP, which could be explained by the
      close functional relation of these proteins.

PMID- 25385676
TI  - Isotopic evidence for divergent diets and mobility patterns in the Atacama
      Desert, northern Chile, during the Late Intermediate Period (AD 900-1450).
AB  - The decline of the Tiwanaku state saw the emergence of two new cultures-Pica
      Tarapaca and Atacama-during the Late Intermediate Period in northern Chile.
      Archeological evidence suggests that both groups practised maize agriculture and
      pastoralism, but that their interaction zones differed significantly. Marine
      resources are common at Pica-Tarapaca sites, even those far from coast, while
      Atacama sites in the desert oases and precordilleran area seem to have directed
      their networks towards the highlands. Here we apply stable carbon, nitrogen, and
      oxygen isotope analysis on human bone and enamel to test dietary patterns and
      residential mobility at two sites, Pica 8 and Quitor 6, representing the Pica
      Tarapaca and Atacama cultures, respectively. Our results show that diet at the
      two sites indeed differed: significant but variable consumption of marine
      resources and maize is indicated at Pica 8, despite being an inland site, while
      diet at Quitor 6 was based mainly on terrestrial resources. The use of seabird
      guano and llama dung as fertilizers and extreme aridity may have contributed to
      the high nitrogen isotope values observed in Pica 8 humans. The delta(18) O
      values in Pica 8 individuals are generally lower than for Quitor in spite of its
      greater distance from the Andes. All three isotopes suggest the presence of at
      least five nonlocals in the 30 measured at Pica 8. This evidence for human
      mobility is consistent with the high levels of trade and interaction observed in
      the archeological record, and begins to quantify the degree of movement of
      specific individuals.

PMID- 25385677
TI  - Targeted hepatitis C antibody testing interventions: a systematic review and meta
      analysis.
AB  - Testing for hepatitis C virus (HCV) infection may reduce the risk of liver
      related morbidity, by facilitating earlier access to treatment and care. This
      review investigated the effectiveness of targeted testing interventions on HCV
      case detection, treatment uptake, and prevention of liver-related morbidity. A
      literature search identified studies published up to 2013 that compared a
      targeted HCV testing intervention (targeting individuals or groups at increased
      risk of HCV) with no targeted intervention, and results were synthesised using
      meta-analysis. Exposure to a targeted testing intervention, compared to no
      targeted intervention, was associated with increased cases detected [number of
      studies (n) = 14; pooled relative risk (RR) 1.7, 95% CI 1.3, 2.2] and patients
      commencing therapy (n = 4; RR 3.3, 95% CI 1.1, 10.0). Practitioner-based
      interventions increased test uptake and cases detected (n = 12; RR 3.5, 95% CI
      2.5, 4.8; and n = 10; RR 2.2, 95% CI 1.4, 3.5, respectively), whereas
      media/information-based interventions were less effective (n = 4; RR 1.5, 95% CI
      0.7, 3.0; and n = 4; RR 1.3, 95% CI 1.0, 1.6, respectively). This meta-analysis
      provides for the first time a quantitative assessment of targeted HCV testing
      interventions, demonstrating that these strategies were effective in diagnosing
      cases and increasing treatment uptake. Strategies involving practitioner-based
      interventions yielded the most favourable outcomes. It is recommended that
      testing should be targeted at and offered to individuals who are part of a
      population with high HCV prevalence, or who have a history of HCV risk behaviour.

PMID- 25385678
TI  - Efficacy of plasmapheresis on donor-specific antibody reduction by HLA
      specificity in post-kidney transplant recipients.
AB  - BACKGROUND: Donor-specific antibodies (DSAs) to HLA antigens can cause acute
      antibody-mediated rejection (AMR) after kidney transplantation (Txp). Therapeutic
      plasma exchange (TPE) has been used for AMR treatment; however, DSA reduction
      rates are inconsistent. We investigated DSA reduction rates by HLA specificity
      and clinical outcome. STUDY DESIGN AND METHODS: Sixty-four courses of TPE for 56
      kidney Txp recipients with high DSA were investigated. Dates of TPE procedures
      and Txp, patients' age, sex, race, creatinine (Cr), and mean fluorescent
      intensity (MFI) of DSA were retrieved. MFI reduction rate after one to three TPE
      and four to six TPE procedures were calculated by HLA DSA specificity in each
      patient, and the mean reduction rates were compared. The relationship of TPE
      treatment, MFI or Cr improvement rate, and graft age was also investigated.
      RESULTS: Patients received a mean 6.0 TPE procedures. Most received intravenous
      immunoglobulin after TPE and immunosuppressives. Forty-two cases (65.6%) had DSA
      to HLA Class I and 54 cases (84.4%) to Class II, including 32 cases (50.0%) to
      both. Mean MFI reduction rates after one to three TPE and four to six TPE
      procedures were 25.7 and 37.1% in HLA Class I, 25.1 and 34.2% in Class II, and
      14.3 and 19.9% in DR51-53. The mean Cr improvements at the end of TPE and 3 and 6
      months after TPE were 3.41, -0.37, and -0.72%, respectively. CONCLUSION: Six TPE
      procedures decreased DSA more than three TPE procedures, but reduction rate was
      lower by the second three TPE procedures than the first three TPE procedures.
      Although the mean Cr improvement was minimal, the treatment has good potential to
      stop further deterioration of kidney function. Better Cr improvement rate is
      correlated with the graft age.

PMID- 25385680
TI  - Canadian hospital seeks to end patenting of human genes.

PMID- 25385679
TI  - The clinical spectrum and therapeutic management of hypocomplementemic urticarial
      vasculitis: data from a French nationwide study of fifty-seven patients.
AB  - OBJECTIVE: Hypocomplementemic urticarial vasculitis (HUV) is an uncommon
      vasculitis of unknown etiology that is rarely described in the literature. We
      undertook this study to analyze the clinical spectrum and the therapeutic
      management of patients with HUV. METHODS: We conducted a French nationwide
      retrospective study that included 57 patients with chronic urticaria, histologic
      leukocytoclastic vasculitis, and hypocomplementemia. We assessed clinical and
      laboratory data and evaluated the patients' cutaneous and immunologic responses
      to therapy. We evaluated treatment efficacy by measuring the time to treatment
      failure. RESULTS: Urticarial lesions were typically more pruritic than painful
      and were associated with angioedema in 51% of patients, purpura in 35%, and
      livedo reticularis in 14%. Extracutaneous manifestations included constitutional
      symptoms (in 56% of patients) as well as musculoskeletal involvement (in 82%),
      ocular involvement (in 56%), pulmonary involvement (in 19%), gastrointestinal
      involvement (in 18%), and kidney involvement (in 14%). Patients with HUV
      typically presented with low C1q levels and normal C1 inhibitor levels, in
      association with anti-C1q antibodies in 55% of patients. Hydroxychloroquine or
      colchicine seemed to be as effective as corticosteroids as first-line therapy. In
      patients with relapsing and/or refractory disease, rates of cutaneous and
      immunologic response to therapy seemed to be higher with conventional
      immunosuppressive agents, in particular, azathioprine, mycophenolate mofetil, or
      cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy.
      Finally, a cutaneous response to therapy was strongly associated with an
      immunologic response to therapy. CONCLUSION: HUV represents an uncommon systemic
      and relapsing vasculitis with various manifestations, mainly, musculoskeletal and
      ocular involvement associated with anti-C1q antibodies, which were found in
      approximately half of the patients. The best strategy for treating HUV has yet to
      be defined.

PMID- 25385682
TI  - An in vivo comparison of internal bacterial colonization in two dental implant
      systems: identification of a pathogenic reservoir.
AB  - OBJECTIVES: The aim of this study was to compare internal bacterial colonization
      in two implant systems, one screw root form (SRF) with an external hexagon
      connection and one plateau root form (PRF) with a Morse taper internal
      connection. MATERIALS AND METHODS: Thirty-two implants; 12 SRF and 20 PRF, were
      sampled in 15 patients. All implants had been in function for at least 6 months
      prior to sampling. The implant restoration was removed and 10 ul of sterile
      saline was introduced into the implant well via a sterile glass syringe. The
      saline was drawn back up and transferred to the laboratory for microbiological
      analysis. The number of aerobic and anaerobic colony forming units per millilitre
      was determined and the dominant micro-organism in each sample was identified by
      16s rRNA gene amplicon sequencing. RESULTS: There was a significant difference
      between bleeding on probing around the SRF implants (3%) and the PRF implants
      (28%) (p = 0.0496). Bacterial colonization was identified at 11 SRF and 19 PRF
      implants. The numbers of anaerobic bacteria recovered from PRF implants was
      significantly higher than that from SRF implants (p = 0.0002). Streptococcus
      species and Enterococcus faecalis were found to dominate. CONCLUSIONS: This in
      vivo study demonstrated bacterial colonization in both types of implant systems,
      irrespective of the type of connection. Significantly greater anaerobic counts
      were found in the Morse taper internal connection implants.

PMID- 25385683
TI  - Does early establishment of favorable oral health behavior influence caries
      experience at age 5 years?
AB  - OBJECTIVE: The purpose was to study associations between tooth brushing
      frequency, use of fluoride lozenges and consumption of sugary drinks at 1.5 years
      of age and having caries experience at 5 years of age. METHODS: This study was
      based on data from the Norwegian Mother and Child Cohort Study conducted by the
      Norwegian Institute of Public Health and by the Public Dental Services. A total
      of 1095 children were followed from pregnancy to the age of 5 years.
      Questionnaires regarding oral health behavior were completed by the parents at
      1.5 and 5 years of age. Clinical and radiographic examination of the children was
      performed at the age of 5 years. RESULTS: In multiple logistic regression, having
      caries experience at 5 years of age was associated with; at 1.5 years of age
      having the teeth brushed less than twice daily (OR = 2.1, CI = 1.3-3.6) and being
      offered sugary drinks at least once a week (OR = 1.8, CI = 1.1-2.9) when
      controlled for family characteristics and oral health behavior at 5 years of age.
      CONCLUSIONS: Tooth brushing frequency and consumption of sugary drinks in early
      childhood were related to caries development during pre-school age, independent
      of family characteristics and oral health behavior at 5 years of age. The results
      indicate that early established habits regarding tooth brushing and consumption
      of sugary drinks have long-term effects on caries development. Parents
      encountering difficulties in establishing favorable oral health behavior in
      children's first years of life should receive special attention from health
      personnel.

PMID- 25385684
TI  - Comparison of mandibular first molar mesial root canal morphology using micro
      computed tomography and clearing technique.
AB  - OBJECTIVE: Micro-computed tomography (MCT) with alternative image reformatting
      techniques shows complex and detailed root canal anatomy. This study compared two
      dimensional (2D) and 3D MCT image reformatting with standard tooth clearing for
      studying mandibular first molar mesial root canal morphology. MATERIALS AND
      METHODS: Extracted human mandibular first molar mesial roots (n=31) were scanned
      by MCT (Skyscan 1172). 2D thin-slab minimum intensity projection (TS-MinIP) and
      3D volume rendered images were constructed. The same teeth were then processed by
      clearing and staining. For each root, images obtained from clearing, 2D, 3D and
      combined 2D and 3D techniques were examined independently by four endodontists
      and categorized according to Vertucci's classification. Fine anatomical
      structures such as accessory canals, intercanal communications and loops were
      also identified. RESULTS: Agreement among the four techniques for Vertucci's
      classification was 45.2% (14/31). The most frequent were Vertucci's type IV and
      then type II, although many had complex configurations that were non
      classifiable. Generally, complex canal systems were more clearly visible in MCT
      images than with standard clearing and staining. Fine anatomical structures such
      as intercanal communications, accessory canals and loops were mostly detected
      with a combination of 2D TS-MinIP and 3D volume-rendering MCT images.
      CONCLUSIONS: Canal configurations and fine anatomic structures were more clearly
      observed in the combined 2D and 3D MCT images than the clearing technique. The
      frequency of non-classifiable configurations demonstrated the complexity of
      mandibular first molar mesial root canal anatomy.

PMID- 25385685
TI  - A pilot randomized controlled trial of a post-discharge program to support
      emerging adults with type 1 diabetes mellitus transition from pediatric to adult
      care.
AB  - AIMS: There is a paucity of randomized controlled trials (RCT) examining
      transition from pediatric to adult care in type 1 diabetes mellitus (T1DM). This
      study aimed to determine if transition in T1DM is more effective with a
      comprehensive transition program (CTP) compared with standard clinical practice
      (SCP). METHODS: This RCT recruited as young people left pediatric diabetes
      services. The trial co-ordinator provided CTP participants with standardized
      telephone communication support at week 1, and 3, 6, and 12 months post-discharge
      from pediatric care. SCP participants were briefly contacted at 6 and 12 months
      post-discharge to confirm transfer status; they received no other post-discharge
      contact as per usual practice. At 12 months, the primary outcomes were engagement
      and retention in the adult service and secondary outcomes included hemoglobin A1c
      (HbA1c), diabetes-related hospitalizations, microvascular complication
      appearance, and global self-worth. RESULTS: Most CTP participants (11/14) and all
      SCP (12/12) participants (P = 0.2) transferred to an adult diabetes service; the
      median time to transfer was 14-15 wk. Overall, participants' frequency of adult
      diabetes service visits was sub-optimal but their retention in adult care was
      high. The only group difference was a higher HbA1c at baseline and follow-up in
      the CTP group. However, a general linear model found that follow-up HbA1c
      increased by 1.2% for each percentage increase in baseline HbA1c [95% confidence
      interval (0.4, 1.9; P = 0.01)], independent of treatment group. CONCLUSIONS:
      Despite the challenges in recruiting adequate numbers, these findings provide
      valuable insights for future T1DM transition RCTs that are needed to build a more
      solid evidence-base in this field.

PMID- 25385687
TI  - Renal tumour anatomical characteristics and functional outcome after partial
      nephrectomy.
AB  - OBJECTIVE: Anatomical features of renal tumours may be useful in predicting
      glomerular filtration rate (GFR) after partial nephrectomy. In this study,
      anatomical classification systems (ACSs) were compared to predict changes in
      renal function after surgery. MATERIALS AND METHODS: A group of 294 patients with
      T1 renal tumours receiving partial nephrectomy between January 2006 and June 2013
      were identified from the institutional kidney tumour database. Preoperative
      images from computed tomography or magnetic resonance imaging were reviewed to
      assess diameter, PADUA (preoperative aspects and dimensions used for an
      anatomical) classification score, RENAL (radius, exophytic/endophytic properties
      of the tumour, nearness of tumour deepest portion to the collecting system or
      sinus, anterior/posterior descriptor and location relative to polar lines)
      nephrometry score, centrality index (C index) and renal tumour invasion index
      (RTII). GFR was estimated using the Modification of Diet in Renal Disease
      equation preoperatively and 3 months after operation. Linear and logistic
      regression were applied as statistical methods. RESULTS: Mean tumour diameter was
      3.0 +/- 2.2 cm (range 1.0-7.0 cm). GFR was 85 +/- 22 ml/min/1.73 m2 before the
      operation and 77 +/- 21 ml/min/1.73 m2 (-8% change) 3 months after the operation.
      In univariate linear regression, the percentage change in GFR was weakly but
      statistically significantly associated with surgical approach (p = 0.04),
      indication for nephron sparing (p = 0.02), preoperative GFR (p < 0.001), PADUA (p
      = 0.02), RENAL (p = 0.01) and RTII (p = 0.003). In multivariate logistic
      regression analysis among patients with tumours 3 cm or larger, PADUA (odds ratio
      1.55, p = 0.021) and RTII (odds ratio 3.87, p = 0.037) predicted at least a 20%
      reduction in GFR. CONCLUSIONS: Renal tumour ACSs may be clinically useful in
      predicting changes in renal function after partial nephrectomy in patients with
      larger tumours. The performance of RTII is equal to that of other ACSs in
      predicting changes in GFR.

PMID- 25385686
TI  - Antibiotic use and associated factors in patients with dementia: a systematic
      review.
AB  - BACKGROUND: Infections frequently occur in patients with dementia and antibiotics
      are often prescribed, but may also be withheld. OBJECTIVES: The aim of this
      systematic review is to provide a systematic overview of the prevalence of
      antibiotic use, and factors associated with prescribing antibiotics in patients
      with dementia. DATA SOURCES: A systematic search of MEDLINE, EMBASE, PSYCINFO,
      CINAHL, and the Cochrane library databases until February 13, 2014 was performed,
      using both controlled terms and free-text terms. RESULTS: Thirty-seven articles
      were included. The point prevalence of antibiotic use in patients with dementia
      ranged from 3.3 to 16.6%. The period prevalence ranged from 4.4 to 88% overall,
      and from 23.5 to 94% in variable time frames before death; the median use was 52%
      (median period 14 days) and 48% (median period 22 days), respectively. Most
      patients with lower respiratory tract infections or urinary tract infections (77
      91%) received antibiotic treatment. Factors associated with antibiotic use
      related to patients, families, physicians, and the healthcare context. More
      severe dementia and a poor prognosis were associated with less antibiotic use in
      various countries. Associations with aspiration and illness severity differed by
      country. CONCLUSIONS AND IMPLICATIONS: Antibiotic use in patients with dementia
      is substantial, and probably highly associated with the particular healthcare
      context. Future studies may report antibiotic use by infection type and stage of
      dementia, and compare cross-nationally.

PMID- 25385688
TI  - BRAF, NRAS and MC1R status in a prospective series of primary cutaneous melanoma.

PMID- 25385689
TI  - Hydrothermal preparation and magnetic properties of NaFeSi2O6: nanowires vs bulk
      samples.
AB  - A single-step hydrothermal route to the preparation of the pyroxene mineral,
      NaFeSi2O6, is reported. The as-prepared samples are found to adopt a nanowire
      morphology and can be made with a yield of several hundred milligrams at a time
      with high purity. Synchrotron X-ray diffraction, electron microscopy, and
      Mossbauer spectroscopy are employed to characterize the structure and morphology.
      A comparison of the temperature- and field-dependent magnetic properties between
      the nanowire and sintered phases shows substantial differences that can likely be
      attributed to the reduced particle size and increased number of spins on the
      surface of the nanowires. 

PMID- 25385690
TI  - Formulation and performance of danazol nano-crystalline suspensions and spray
      dried powders.
AB  - PURPOSE: This study focuses on the formulation optimization, in vitro and in vivo
      performance of differently sized nano-crystalline liquid suspensions and spray
      dried powders of a poorly soluble BCS class II compound i.e. Danazol. METHODS: A
      DoE approach was utilized to optimize stabilizer concentration and formulate
      danazol (BCS class II) nano-crystalline suspensions and dry powders via wet
      milling followed by spray drying. Solubility studies were performed to select
      best stabilizers. Particle size, PXRD, contact angle measurement and in vitro
      dissolution were utilized in characterization of the liquid and spray-dried
      powder formulations. RESULTS: The liquid nano-crystalline suspensions followed
      particle size-dependent dissolution rates i.e. faster dissolution for smaller
      crystals. The spray-dried nano-crystal powders did not show fast dissolution
      profiles compared to the liquid nano-crystalline suspension. The poor dissolution
      of the spray-dried powder correlated to its high LogP value (i.e. LogP 4.53) and
      poor wetting (or polar surface-area). In vivo bioavailability studies showed
      superior performance of the liquid nano-crystalline suspensions compared to other
      milled and un-milled formulations. CONCLUSION: Wet-milling and spray-drying
      optimization for danazol nano-crystalline suspension was performed. This study
      indicates that drug candidates with high LogP values and low polar surface area
      may not be suitable for formulation as dry nano-crystals.

PMID- 25385691
TI  - Evidences of in vivo bioactivity of Fe-bioceramic composites for temporary bone
      implants.
AB  - Iron-bioceramic composites have been developed as biodegradable implant materials
      with tailored degradation behavior and bioactive features. In the current work,
      in vivo bioactivity of the composites was comprehensively studied by using sheep
      animal model. Five groups of specimens (Fe-HA, Fe-TCP, Fe-BCP composites, and
      pure-Fe and SS316L as controls) were surgically implanted into medio proximal
      region of the radial bones. Real-time ultrasound analysis showed a decreased echo
      pattern at the peri-implant biodegradation site of the composites indicating
      minimal tissue response during the wound healing process. Peripheral whole blood
      biomarkers monitoring showed a normal dynamic change of blood cellular responses
      and no stress effect was observed. Meanwhile, the released Fe ion concentration
      was increasing along the implantation period. Histological analysis showed that
      the composites corresponded with a lower inflammatory giant cell count than that
      of SS316L. Analysis of the retrieved implants showed a thicker degradation layer
      on the composites compared with pure-Fe. It can be concluded that the iron
      bioceramic composites are bioactive and induce a preferable wound healing
      process.

PMID- 25385692
TI  - Cancer Research Participation Beliefs and Behaviors of a Southern Black
      Population: A Quantitative Analysis of the Role of Structural Factors in Cancer
      Research Participation.
AB  - Increasing the participation of Blacks in cancer research is a vital component of
      a strategy to reduce racial inequities in cancer burden. Community-based
      participatory research (CBPR) is especially well-suited to advancing our
      knowledge of factors that influence research participation to ultimately address
      cancer-related health inequities. A paucity of literature focuses on the role of
      structural factors limiting participation in cancer research. As part of a larger
      CBPR project, we used survey data from a statewide cancer needs assessment of a
      Black faith community to examine the influence of structural factors on attitudes
      toward research and the contributions of both structural and attitudinal factors
      on whether individuals participate in research. Regression analyses and non
      parametric statistics were conducted on data from 727 adult survey respondents.
      Structural factors, such as having health insurance coverage, experiencing
      discrimination during health care encounters, and locale, predicted belief in the
      benefits, but not the risks, of research participation. Positive attitudes toward
      research predicted intention to participate in cancer research. Significant
      differences in structural and attitudinal factors were found between cancer
      research participants and non-participants; however, directionality is confounded
      by the cross-sectional survey design and causality cannot be determined. This
      study points to complex interplay of structural and attitudinal factors on
      research participation as well as need for additional quantitative examinations
      of the various types of factors that influence research participation in Black
      communities. 

PMID- 25385693
TI  - Engaging Immigrant and Refugee Women in Breast Health Education.
AB  - This project assessed the impact of a community-based educational program on
      breast cancer knowledge and screening among Buffalo (NY) immigrant and refugee
      females. Program participants completed language-matched pre- and post-test
      assessments during a single session educational program; breast cancer screening
      information was obtained from the mobile mammography unit to which participants
      were referred. Pre- and post-test knowledge scores were compared to assess
      changes in responses to each of the six individual knowledge items, as well as
      overall. Mammogram records were reviewed to identify Breast Imaging Reporting and
      Data System (BI-RADS) scores. The proportion of correct responses to each of the
      six knowledge items increased significantly on the post-program assessments; 33 %
      of women >40 years old completed mammograms. The findings suggest that a health
      education program for immigrant and refugee women, delivered in community-based
      settings and involving interpreters, can enhance breast cancer knowledge and lead
      to improvements in mammography completion.

PMID- 25385694
TI  - The St. Jude Cancer Education for Children Program Pilot Study: Determining the
      Knowledge Acquisition and Retention of 4th-Grade Students.
AB  - In 2006, St. Jude Children's Research Hospital began developing a school-based
      outreach program known as the St. Jude Cancer Education for Children Program
      (SJCECP). The program aimed to teach children about cancer and healthy habits
      that can prevent the formation of cancers into adulthood. During the 2010-2011
      academic years, we conducted a pilot evaluation of the SJCECP curriculum, with
      the primary objective of evaluating the impact of the intervention on knowledge
      acquisition and retention among 4th-grade students participating in the program.
      Seven local schools and 481 students from the Memphis area participated in the
      program evaluation. The results of this study show that 4th-grade students are
      able to acquire gains in knowledge related to cells, cancer, and healthy living
      after receiving the SJCECP intervention. We conclude that the program can be a
      useful tool for improving knowledge of cancer concepts at the 4th-grade level. 

PMID- 25385695
TI  - Damage Control Resuscitation.
AB  - Resuscitation of the hemorrhaging patient has undergone significant changes in
      the last decade resulting in the concept of damage control resuscitation (DCR).
      Hemostatic resuscitation aims to address the physiologic derangements found in
      the hemorrhaging patient, namely coagulopathy, acidosis, and hypothermia.
      Strategies to achieve this are permissive hypotension, high ratio of plasma and
      platelet transfusion to packed red blood cell transfusion, and limitation of
      crystalloid administration. Damage control surgery aims for early hemorrhage
      control and minimizing operative time by delaying definitive repair until the
      patient's physiologic status has normalized. Together these strategies constitute
      DCR and have led to improved outcomes for hemorrhaging patients over the last 2
      decades. Recently, DCR has been augmented by both pharmacologic and laboratory
      adjuncts to improve the care of the hemorrhaging patient. These include
      thrombelastography as a detailed measure of the clotting cascade, tranexamic acid
      as an antifibrinolytic, and the procoagulant activated factor VII. In this
      review, we discuss the strategies that makeup DCR, their adjuncts, and how they
      fit into the care of the hemorrhaging patient. 

PMID- 25385697
TI  - Iron and ferritin dependent ROS distribution impact Arabidopsis root system
      architecture.
AB  - Iron (Fe) homeostasis is integrated with the production of Reactive Oxygen
      Species (ROS) whose distribution at the root tip participates in the control of
      root growth. Excess Fe increases ferritin abundance, enabling the storage of Fe
      which contributes to protection of plants against Fe-induced oxidative stress.
      AtFer1 and AtFer3 are the two ferritin genes expressed in the meristematic zone,
      pericycle and endodermis of the Arabidopsis thaliana (Arabidopsis) root, and it
      is in these regions that we observe Fe stained dots. This staining disappears in
      the triple fer1-3-4 ferritin mutant. Fe excess decreases primary root length in
      the same way in wild-type and in fer1-3-4 mutant. In contrast, the Fe mediated
      decrease of lateral root (LR) length and density is enhanced in fer1-3-4 plants
      due to a defect in LR emergence. We observe that this interaction between excess
      Fe, ferritin and RSA is in part mediated by the H2O2/O2.- balance between the
      root cell proliferation and differentiation zones regulated by the UPB1
      transcription factor. Further, meristem size is also decreased in response to Fe
      excess in ferritin mutant plants, implicating cell cycle arrest mediated by the
      ROS-activated SMR5/SMR7 cyclin-dependent kinase inhibitors pathway in the
      interaction between Fe and RSA.

PMID- 25385699
TI  - ROP GTPase Regulation of Auxin Transport in Arabidopsis.

PMID- 25385698
TI  - Multifaceted regulations of gateway enzyme phenylalanine ammonia-lyase in the
      biosynthesis of phenylpropanoids.
AB  - Phenylpropanoid biosynthesis in plants engenders a vast variety of aromatic
      metabolites critically important for their growth, development, and environmental
      adaptation. Some of these aromatic compounds have high economic value.
      Phenylalanine ammonia-lyase (PAL) is the first committed enzyme in the pathway;
      it diverts the central flux of carbon from primary metabolism to the synthesis of
      myriad phenolics. Over the decades, many studies have shown that exquisite
      regulatory mechanisms at multiple levels control the transcription and the
      enzymatic activity of PALs. In this review, we present a current overview on our
      understanding of the complicated regulatory mechanisms governing PAL's activity;
      we particularly highlight recent progresses in unraveling its post-translational
      modifications, its metabolite feedback regulation, and its enzyme organization.

PMID- 25385700
TI  - Designing Microarray and RNA-seq Experiments for Greater Systems Biology
      Discovery in Modern Plant Genomics.
AB  - Microarray and RNA-seq experiments have become an important part of modern
      genomics and systems biology. Obtaining meaningful biological data from these
      experiments is an arduous task that demands close attention to many details.
      Negligence at any step can lead to gene expression data containing inadequate or
      composite information that is recalcitrant for pattern extraction. Therefore, it
      is imperative to carefully consider experimental design before launching a time
      consuming and costly experiment. Contemporarily, most genomics experiments have
      two objectives: (1) generate two or more groups of comparable data for
      identifying differentially expressed genes, gene families, biological processes,
      or metabolic pathways under experimental condition. (2) build local gene
      regulatory networks and identify hierarchically important regulators governing
      biological processes and pathways of interest. Since the first objective aims to
      identify the active molecular identities and the second provides a basis for
      understanding the underlying molecular mechanisms through inferring causality
      relationships mediated by treatment, an optimal experiment is to produce
      biologically relevant and extractable data to meet both objectives without
      substantially increasing the cost. This review discussed the major issues that
      researchers commonly face when embarking on a microarray or RNA-seq experiments
      and summarized important aspects of experimental design, which aim to help
      researchers deliberate how to generate gene expression profiles with low
      background noise but more interaction to facilitate novel biological knowledge
      discoveries in modern plant genomics.

PMID- 25385701
TI  - XA23 is an executor R protein and confers broad-spectrum disease resistance in
      rice.
AB  - The majority of plant disease resistance (R) genes encode proteins that share
      common structural features. However, the transcription activator-like effector
      (TALE) associated executor type R genes show no considerable sequence homology to
      any known R genes. We adopted a map-based cloning approach and TALE-based
      technology to isolate and characterize Xa23, a new executor R gene derived from
      the wild rice (Oryza rufipogon) that confers an extremely broad spectrum of
      resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo).
      Xa23 encodes a 113-amino acid protein that shares 50% identity to the known
      executor R protein XA10. The predicted transmembrane helices in XA23 also overlap
      with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically
      activated by AvrXa23, a TALE present in all examined Xoo field isolates.
      Moreover, the susceptible xa23 allele has an identical open reading frame of
      Xa23, but differs in promoter region by lacking the TALE binding-element (EBE)
      for AvrXa23. XA23 can trigger strong hypersensitive response in rice, tobacco and
      tomato. Our results provide the first evidence that plant genomes have an
      executor R gene family in which members execute their function and spectrum of
      disease resistance by recognizing the cognate TALEs in pathogen.

PMID- 25385702
TI  - A pilot examination of the use of narrative therapy with individuals diagnosed
      with PTSD.
AB  - Narrative therapy is a postmodern, collaborative therapy approach based on the
      elaboration of personal narratives for lived experiences. Many aspects of
      narrative therapy suggest it may have great potential for helping people who are
      negatively affected by traumatic experiences, including those diagnosed with
      posttraumatic stress disorder (PTSD). The potential notwithstanding, narrative
      therapy is relatively untested in any population, and has yet to receive
      empirical support for treatment among survivors of trauma. A pilot investigation
      of the use of narrative therapy with 14 veterans with a diagnosis of PTSD (11
      treatment completers) is described. Participants completed structured diagnostic
      interviews and self-report assessments of symptoms prior to and following 11 to
      12 sessions of narrative therapy. After treatment, 3 of 11 treatment completers
      no longer met criteria for PTSD and 7 of 11 had clinically significant decreases
      in PTSD symptoms as measured by the Clinician Administered PTSD Scale. Pre- to
      posttreatment effect sizes on outcomes ranged from 0.57 to 0.88. These
      preliminary results, in conjunction with low rates of treatment dropout (21.4%)
      and a high level of reported satisfaction with the treatment, suggest that
      further study of narrative therapy is warranted as a potential alternative to
      existing treatments for PTSD. 

PMID- 25385704
TI  - Patient adherence: clinical pharmacology's embarrassing relative.

PMID- 25385703
TI  - Exploring the potential of monoclonal antibody therapeutics for HIV-1
      eradication.
AB  - The HIV field has seen an increased interest in novel cure strategies. In
      particular, new latency reversal agents are in development to reverse latency to
      flush the virus out of its hiding place. Combining these efforts with
      immunotherapeutic approaches may not only drive the virus out of latency, but
      allow for the rapid elimination of these infected cells in a "shock and kill"
      approach. Beyond cell-based approaches, growing interest lies in the potential
      use of functionally enhanced "killer" monoclonal therapeutics to purge the
      reservoir. Here we discuss prospects for a monoclonal therapeutic-based "shock
      and kill" strategy that may lead to the permanent elimination of replication
      competent virus, making a functional cure a reality for all patients afflicted
      with HIV worldwide.

PMID- 25385705
TI  - High-frequency binge eating predicts weight gain among veterans receiving
      behavioral weight loss treatments.
AB  - OBJECTIVE: To assess for the frequency of binge eating behavior and its
      association with weight loss in an overweight/obese sample of veterans. METHODS:
      This study is a secondary analysis of data from the ASPIRE study, a randomized
      effectiveness trial of weight loss among veterans. Of the 481 enrolled veterans
      with overweight/obesity, binge eating frequency was obtained by survey for 392
      (82%). RESULTS: The majority (77.6%) reported binge eating, and 6.1% reported
      high-frequency binge eating. Those reporting any binge eating lost 1.4% of body
      weight, decreased waist circumference by 2.0 cm, and had significantly worse
      outcomes than those reporting never binge eating who lost about double the weight
      (2.7%) and reduced waist circumference by twice as much (4.2 cm). The high
      frequency binge group gained 1.4% of body weight and increased waist
      circumference by 0.3 cm. CONCLUSIONS: High rates of binge eating were observed in
      an overweight/obese sample of veterans enrolled in weight loss treatment. The
      presence of binge eating predicted poorer weight loss outcomes. Furthermore, high
      frequency binge eating was associated with weight gain. These findings have
      operational and policy implications for developing effective strategies to
      address binge eating in the context of behavioral weight loss programs for
      veterans.

PMID- 25385706
TI  - fQRS as a noninvasive marker for an overgrowing epidemy affecting both aortic
      valve and myocardium in the era of aging population.

PMID- 25385707
TI  - Analysis of the trajectory of osteoarthritis development in a mouse model by
      serial near-infrared fluorescence imaging of matrix metalloproteinase activities.
AB  - OBJECTIVE: A major hurdle in osteoarthritis (OA) research is the lack of
      sensitive detection and monitoring methods. It is hypothesized that proteases,
      such as matrix metalloproteinases (MMPs), are up-regulated in the early stages of
      OA development. This study was undertaken to investigate if a near-infrared (NIR)
      fluorescent probe activated by MMPs could visualize in vivo OA progression
      beginning in the early stages of the disease. METHODS: Using an MMP-activatable
      NIR fluorescent probe (MMPSense 680), we assessed the up-regulation of MMP
      activity in vitro by incubating human chondrocytes with the proinflammatory
      cytokine interleukin-1beta (IL-1beta). MMP activity was then evaluated in vivo
      serially in a mouse model of chronic, injury-induced OA. To track MMP activity
      over time, mice were imaged 1-8 weeks after OA-inducing surgery. Imaging results
      were correlated with histologic findings. RESULTS: In vitro studies confirmed
      that NIR fluorescence imaging identified enhanced MMP activity in IL-1beta
      treated human chondrocytes. In vivo imaging showed significantly higher
      fluorescence intensity in OA knees compared to sham-operated (control) knees of
      the same mice. Additionally, the total emitted fluorescence intensity steadily
      increased over the entire course of OA progression that was examined. NIR
      fluorescence imaging results correlated with histologic findings, which showed an
      increase in articular cartilage structural damage over time. CONCLUSION: Imaging
      of MMP activity in a mouse model of OA provides sensitive and consistent
      visualization of OA progression, beginning in the early stages of OA. In addition
      to facilitating the preclinical study of OA modulators, this approach has the
      potential for future translation to humans.

PMID- 25385712
TI  - Cancer registration system: an introduction.

PMID- 25385710
TI  - Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI
      and Electrophysiology.
AB  - The human default mode network (DMN) shows decreased blood oxygen level dependent
      (BOLD) signals in response to a wide range of attention-demanding tasks. Our
      understanding of the specifics regarding the neural activity underlying these
      "task-negative" BOLD responses remains incomplete. We paired oxygen polarography,
      an electrode-based oxygen measurement technique, with standard
      electrophysiological recording to assess the relationship of oxygen and neural
      activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and
      visually responsive task-positive area V3 in the awake macaque. In response to
      engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC
      showed transient activation followed by sustained suppression. In V3, oxygen, LFP
      power, and multi-unit activity showed an initial phasic response to the stimulus
      followed by sustained activation. Oxygen responses were correlated with LFP power
      in both areas, although the apparent hemodynamic coupling between oxygen level
      and electrophysiology differed across areas. Our results suggest that oxygen
      responses reflect changes in LFP power and multi-unit activity and that either
      the coupling of neural activity to blood flow and metabolism differs between PCC
      and V3 or computing a linear transformation from a single LFP band to oxygen
      level does not capture the true physiological process. 

PMID- 25385711
TI  - Dental caries experience and periodontal treatment needs of children with
      autistic spectrum disorder.
AB  - AIM: To assess dental caries experience and periodontal treatment needs among
      Libyan children diagnosed with autistic spectrum disorder (ASD). MATERIALS AND
      METHODS: A cross-sectional, comparative case-control study was used, in which
      dental caries experience of 50 children with ASD was compared with that of 50
      controls. The children with ASD were recruited from Benghazi Centre of Children
      with ASD, Libya. Controls were recruited from school children and matched for
      age, gender and socioeconomic status. DMFT, dmft for dental caries experience and
      CPITN for periodontal treatment needs were calculated according to WHO criteria
      by a calibrated examiner. Scores for DMFT as well as CPITN indices were compared
      using bivariate analysis. RESULTS: The data analysed for this study comprised
      observations from a group of children (cases = 50) diagnosed with ASD matched
      with healthy children (controls = 50). Consequently, each group consisted of 40
      males and 10 females aged between 3 and 14 years (mean 7.29 +/- 3.11). The ASD
      children showed significantly lower means for DMFT and dmft teeth as well as
      higher periodontal treatment needs (p > 0.05). CONCLUSION: Children with ASD were
      found to be more likely caries-free and have lower DMFT scores and higher unmet
      periodontal treatment needs than did the unaffected control children.

PMID- 25385713
TI  - Recombinant human soluble thrombomodulin (thrombomodulin alfa) to treat
      disseminated intravascular coagulation in solid tumors: results of a one-arm
      prospective trial.
AB  - BACKGROUND: Disseminated intravascular coagulation (DIC) associated with solid
      tumors (DIC-ST) is often encountered in clinical practice. Patients with DIC-ST
      are usually in poor condition and have bleeding diathesis due to advanced or
      metastatic diseases. Although some affected patients are treated with heparin,
      this strategy has not been prospectively studied. Recombinant human soluble
      thrombomodulin (thrombomodulin alfa, TM-alpha) is a new anticoagulant developed
      in Japan. We conducted a prospective study that evaluated the efficacy and safety
      of TM-alpha in patients with DIC-ST. METHODS: A prospective one-arm study with TM
      alpha was conducted for DIC-ST. TM-alpha (380 U/kg) was given for 30 min
      intravenously once daily for 6-14 days. The primary efficacy endpoint was the DIC
      resolution rate. Change in DIC scores and improvement in bleeding symptoms and
      outcomes were also evaluated. Safety endpoints included the incidence of bleeding
      related adverse events. RESULTS: A total of 101 patients were treated with TM
      alpha. The three main underlying malignant diseases were lung, stomach, and
      breast cancer, which accounted for 60 % of all patients. The DIC resolution rate
      was 34.0 % at the end of TM-alpha treatment. Improvement in DIC scores was seen
      in 55.2 % of patients, while only 22.9 % of patients had worsening of DIC scores.
      The overall survival rate was 55.4 % on day 28. The incidence of hemorrhage
      related to TM-alpha was 12.9 % until day 28. Cases of severe hemorrhage related
      to TM-alpha did not occur. CONCLUSIONS: TM-alpha is effective and safe for DIC
      ST. This agent is the treatment of choice for the management of DIC-ST.

PMID- 25385714
TI  - Peers back proposal that a judge would need to approve cases of assisted dying.

PMID- 25385715
TI  - Detection of aneugenicity and clastogenicity in buccal epithelial cells of pan
      masala and gutkha users by pan-centromeric FISH analysis.
AB  - Chewing of betel quid, smoking and alcohol consumption are all associated with
      higher incidences of oral cancer. Genetic damage can be detected by fluorescent
      in situ hybridization (FISH) using human centromeric probes. In the present study
      FISH was performed on buccal epithelial cells of pan masala and gutkha chewers
      alone with and without additional tobacco smoking and/or alcohol consumption. The
      study comprised of 1500 male individuals. The present study found the highest
      frequency of micronuclei without a centromeric region (MN(-)) among gutkha users
      who also smoked and drank (P < 0.05). A significant increase in cells having
      micronuclei with a centromeric region (MN(+)) was observed among pan masala users
      who also smoked (P < 0.05). The study reveals that the clastogenic effects of pan
      masala/gutkha increase with smoking and alcohol consumption, but aneugenic
      effects were also observed among the pan masala chewers who smoked. 

PMID- 25385717
TI  - An on-chip small intestine-liver model for pharmacokinetic studies.
AB  - Testing of drug effects and cytotoxicity by using cultured cells has been widely
      performed as an alternative to animal testing. However, the estimation of
      pharmacokinetics by conventional cell-based assay methods is difficult because of
      the inability to evaluate multiorgan effects. An important challenge in the field
      is to mimic the organ-to-organ network in the human body by using a microfluidic
      network connecting small-scale tissues based on recently emerging MicroTAS (Micro
      Total Analysis Systems) technology for prediction of pharmacokinetics. Here, we
      describe an on-chip small intestine-liver coupled model for pharmacokinetic
      studies. To construct an in vitro pharmacokinetic model that appropriately models
      in vivo conditions, physiological parameters such as the structure of internal
      circulation, volume ratios of each organ, and blood flow ratio of the portal vein
      to the hepatic artery were mimicked using microfluidic networks. To demonstrate
      interactions between organs in vitro in pharmacokinetic studies, Caco-2, HepG2,
      and A549 cell cultures were used as organ models of the small intestine, liver,
      and lung, respectively, and connected to each other through a microporous
      membrane and microchannels to prepare a simple model of a physiological organ-to
      organ network. The on-chip organ model assay using three types of substrate
      epirubicine (EPI), irinotecan (CPT-11), and cyclophosphamide (CPA)-were conducted
      to model the effects of orally administered or biologically active anticancer
      drugs. The result suggested that the device can replicate physiological phenomena
      such as activity of the anticancer drugs on the target cells. This microfluidic
      device can thus be used as an in vitro organ model to predict the
      pharmacokinetics of drugs in the human body and may thus provide not only an
      alternative to animal testing but also a method of obtaining parameters for in
      silico models of physiologically based pharmacokinetics. 

PMID- 25385716
TI  - Biomimetic 3D Tissue Models for Advanced High-Throughput Drug Screening.
AB  - Most current drug screening assays used to identify new drug candidates are 2D
      cell-based systems, even though such in vitro assays do not adequately re-create
      the in vivo complexity of 3D tissues. Inadequate representation of the human
      tissue environment during a preclinical test can result in inaccurate predictions
      of compound effects on overall tissue functionality. Screening for compound
      efficacy by focusing on a single pathway or protein target, coupled with
      difficulties in maintaining long-term 2D monolayers, can serve to exacerbate
      these issues when using such simplistic model systems for physiological drug
      screening applications. Numerous studies have shown that cell responses to drugs
      in 3D culture are improved from those in 2D, with respect to modeling in vivo
      tissue functionality, which highlights the advantages of using 3D-based models
      for preclinical drug screens. In this review, we discuss the development of
      microengineered 3D tissue models that accurately mimic the physiological
      properties of native tissue samples and highlight the advantages of using such 3D
      microtissue models over conventional cell-based assays for future drug screening
      applications. We also discuss biomimetic 3D environments, based on engineered
      tissues as potential preclinical models for the development of more predictive
      drug screening assays for specific disease models. 

PMID- 25385719
TI  - High-volume online haemodiafiltration improves erythropoiesis-stimulating agent
      (ESA) resistance in comparison with low-flux bicarbonate dialysis: results of the
      REDERT study.
AB  - BACKGROUND: In haemodialysis (HD) patients, anaemia is associated with reduced
      survival. Despite treatment with erythropoiesis-stimulating agents (ESAs), a
      large number of patients with chronic kidney disease show resistance to this
      therapy and require much higher than usual doses of ESAs in order to maintain the
      recommended haemoglobin (Hb) target, and recent studies suggest that hepcidin
      (HEP) may mediate the ESA resistance index (ERI). High-volume online
      haemodiafiltration (HV-OL-HDF) has been shown to improve anaemia and to reduce
      the need for ESAs in HD patients; this effect is associated with a reduced
      inflammatory state in these patients. The aim of the REDERT study (role of
      haemodiafiltration on ERI) was to investigate the effect of different dialysis
      techniques on ERI and HEP levels in chronic dialysis patients. METHODS: A single
      cross-over, randomized, multicentre study (A-B or B-A) was designed. Forty stable
      HD patients from seven different dialysis units (male 65%, mean age 67.6 +/- 14.7
      years and mean dialytic age 48 +/- 10 months) were enrolled. Patients were
      randomized to the standard bicarbonate dialysis (BHD) with low-flux polysulfone
      (PS) membrane group or to the HV-OL-HDF group with high-flux PS membranes and
      exchange volume of >20 L/session. After 6 months, patients were shifted to the
      other dialytic group for a further 6 months. Clinical data, Hb, ESA doses and
      iron metabolism were recorded every month. HEP, beta2-microglobulin (b2MG) and C
      reactive protein (CRP) were determined every 3 months, and ERI was calculated
      monthly as the weekly ESA dose per kilogram of body weight divided by Hb level.
      Data were analysed using paired-samples t-test, Wilcoxon signed-rank test and
      Spearman's correlation coefficient. RESULTS: Dialysis efficiency for small
      molecules assessed as Kt/V was significantly increased in HV-OL-HDF from 1.47 +/-
      0.24 to 1.49 +/- 0.16; P < 0.01. A significant reduction of b2MG was obtained in
      HV-OL-HDF from month 3 whereas CRP values were not significantly changed during
      the study period either in BHD or HV-OL-HDF.ERI was significantly reduced in HV
      OL-HDF at month 3 and 6 (from 9.1 +/- 6.4 UI/weekly/Kg/Hb to 6.7 +/- 5.3
      UI/weekly/Kg/Hb; P < 0.05) due to a higher ESA consumption in BHD in spite of
      similar Hb levels. HEP levels were reduced in HV-OL-HDF with respect to BHD after
      3 and 6 months. Iron consumption was not significantly different during BHD or HV
      OL-HDF treatment as well as transferrin, ferritin and TSAT levels. A significant
      positive linear correlation between HEP and ERI (r(2) = 0.258, P < 0.001) was
      observed. CONCLUSIONS: In a uraemic patient population with low-grade
      inflammation treated with HV-OL-HDF, we observed a significant reduction of ERI
      values as well as HEP levels. The positive correlation between these two
      parameters supports a role for HEP in the development of ERI in the dialytic
      population. Moreover, the lower b2MG and the higher Kt/V achieved in HV-OL-HDF
      confirms the better depurative effect of this technique in comparison with BHD
      with respect to middle molecules and small-molecular-weight molecules.

PMID- 25385720
TI  - Tri-ortho-cresyl phosphate induces autophagy of rat spermatogonial stem cells.
AB  - Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic
      softeners, and flame retardants in industry and reported to have a deleterious
      effect on the male reproductive system in animals besides delayed neurotoxicity.
      Our preliminary results found that TOCP could disrupt the seminiferous epithelium
      in the testis and inhibit spermatogenesis, but the precise mechanism is yet to be
      elucidated. This study shows that TOCP inhibited viability of rat spermatogonial
      stem cells in a dose-dependent manner. TOCP could not lead to cell cycle arrest
      in the cells; the mRNA levels of p21, p27, p53, and cyclin D1 in the cells were
      also not affected by TOCP. Meanwhile, TOCP did not induce apoptosis of rat
      spermatogonial stem cells. After treatment with TOCP, however, both LC3-II and
      the ratio of LC3-II/LC3-I were markedly increased; autophagy proteins ATG5 and
      beclin 1 were also increased after treatment with TOCP, indicating that TOCP
      could induce autophagy in the cells. Ultrastructural observation under the
      transmission electron microscopy indicated that autophagic vesicles in the
      cytoplasm containing extensively degraded organelles such as mitochondria and
      endoplasmic reticulum increased significantly after the cells were treated with
      TOCP. In summary, we have shown that TOCP can inhibit viability of rat
      spermatogonial stem cells and induce autophagy of the cells, without affecting
      cell cycle and apoptosis. 

PMID- 25385721
TI  - Oxidative stress impairs function and increases redox protein modifications in
      human spermatozoa.
AB  - Oxidative stress, generated by excessive reactive oxygen species (ROS) or
      decreased antioxidant defenses (and possibly both), is associated with male
      infertility. Oxidative stress results in redox-dependent protein modifications,
      such as tyrosine nitration and S-glutathionylation. Normozoospermic sperm samples
      from healthy individuals were included in this study. Samples were incubated with
      increasing concentrations (0-5 mM) of exogenous hydrogen peroxide, tert-butyl
      hydroperoxide, or diethylamine NONOate (DA-NONOate, a nitric oxide (NO?) donor)
      added to the medium. Spermatozoa treated with or without ROS were incubated under
      capacitating conditions and then levels of tyrosine phosphorylation and
      percentage of acrosome reaction (AR) induced by lysophosphatidylcholine were
      determined. Modified sperm proteins from cytosolic, triton-soluble, and triton
      insoluble fractions were analyzed by SDS-PAGE immunoblotting and
      immunocytochemistry with anti-glutathione and anti-nitrotyrosine antibodies.
      Levels of S-glutathionylation increased dose dependently after exposure to
      hydroperoxides (P<0.05) and were localized mainly to the cytosolic and triton
      soluble fractions of the spermatozoa. Levels of tyrosine-nitrated proteins
      increased dose dependently after exposure to DA-NONOate (P<0.05) and were mainly
      localized to the triton-insoluble fraction. ROS-treated spermatozoa showed
      impaired motility without affecting viability (hypo-osmotic swelling test). These
      treated spermatozoa had tyrosine phosphorylation and AR levels similar to that of
      non-capacitated spermatozoa following incubation under capacitating conditions,
      suggesting an impairment of sperm capacitation by oxidative stress. In
      conclusion, oxidative stress promotes a dose-dependent increase in tyrosine
      nitration and S-glutathionylation and alters motility and the ability of
      spermatozoa to undergo capacitation.Free Spanish abstractA Spanish translation of
      this abstract is freely available at http://www.reproduction
      online.org/content/149/1/113/suppl/DC1. 

PMID- 25385723
TI  - Reply to L. Alonso et al.

PMID- 25385722
TI  - Requirement of the transcription factor USF1 in bovine oocyte and early embryonic
      development.
AB  - Upstream stimulating factor 1 (USF1) is a basic helix-loop-helix transcription
      factor that specifically binds to E-box DNA motifs, known cis-elements of key
      oocyte expressed genes essential for oocyte and early embryonic development.
      However, the functional and regulatory role of USF1 in bovine oocyte and embryo
      development is not understood. In this study, we demonstrated that USF1 mRNA is
      maternal in origin and expressed in a stage specific manner during the course of
      oocyte maturation and preimplantation embryonic development. Immunocytochemical
      analysis showed detectable USF1 protein during oocyte maturation and early
      embryonic development with increased abundance at 8-16-cell stage of embryo
      development, suggesting a potential role in embryonic genome activation.
      Knockdown of USF1 in germinal vesicle stage oocytes did not affect meiotic
      maturation or cumulus expansion, but caused significant changes in mRNA abundance
      for genes associated with oocyte developmental competence. Furthermore, siRNA
      mediated depletion of USF1 in presumptive zygote stage embryos demonstrated that
      USF1 is required for early embryonic development to the blastocyst stage. A
      similar (USF2) yet unique (TWIST2) expression pattern during oocyte and early
      embryonic development for related E-box binding transcription factors known to
      cooperatively bind USF1 implies a potential link to USF1 action. This study
      demonstrates that USF1 is a maternally derived transcription factor required for
      bovine early embryonic development, which also functions in regulation of JY1,
      GDF9, and FST genes associated with oocyte competence. 

PMID- 25385724
TI  - Cognitive outcome after pediatric stem-cell transplantation: impact of age and
      total-body irradiation.
AB  - PURPOSE: To examine the influence of age and conditioning with total-body
      irradiation (TBI) on the trajectory of cognitive functioning after treatment with
      pediatric hematopoietic stem-cell transplantation (SCT). PATIENTS AND METHODS:
      Pediatric patients who were scheduled to undergo a SCT were eligible for the
      study, with 315 patients completing a baseline assessment. Of these, 183 patients
      (58.1%) were alive at 1 year after SCT and completed additional assessments at 1,
      3, and 5 years after SCT. Half of the long-term sample (52.1%) received TBI
      during conditioning. Cognitive functioning was assessed via age-appropriate
      standardized measures. RESULTS: At baseline, there were no differences in
      intelligence quotient (IQ) based on age. At 5 years after SCT, the youngest
      patients (< 3 years old at baseline) who received TBI demonstrated a
      significantly lower IQ than those who did not receive TBI (P = .05). Longitudinal
      analyses (piecewise linear mixed-effects models with a knot at 1 year after SCT)
      revealed a significant impact of age and TBI over time. The youngest patients
      evidenced declines in cognitive functioning during the first year; however,
      patients who did not receive TBI largely recovered their functioning in
      subsequent years. In contrast, young patients who received TBI failed to recover
      the losses experienced during the first year after SCT, demonstrating stability
      in their functioning, but at a lower level. CONCLUSION: Our findings clarify the
      relationship between TBI and age on cognitive outcomes in pediatric SCT
      survivors. Young patients who receive TBI may benefit from early intervention
      efforts to minimize cognitive losses during the first year after SCT and to
      maximize potential recovery.

PMID- 25385725
TI  - Inequalities in premature death from colorectal cancer by state.
AB  - PURPOSE: Although disparities in colorectal cancer (CRC) with regard to race,
      socioeconomic status, and geography are well documented, the extent to which
      these factors contribute to premature death resulting from CRC nationwide and by
      state is unknown. PATIENTS AND METHODS: We calculated age-standardized CRC death
      rates for three broad educational categories as a marker of socioeconomic status
      by race/ethnicity and state among individuals age 25 to 64 years from 2008
      through 2010. We also calculated the proportion of premature death resulting from
      CRC that could potentially be averted in each state by applying the average death
      rate for the five states with the lowest rates among the most educated whites
      (Connecticut, North Dakota, Utah, Vermont, and Wisconsin) to all populations.
      RESULTS: Compared with those with the most education, those with the least
      education had significantly higher CRC death rates in virtually all states for
      each racial/ethnic group. For example, rate ratios ranged from 1.15 (95% CI, 0.66
      to 2.01) in Delaware to 3.18 (95% CI, 2.01 to 5.05) in New Mexico among whites.
      Overall, half the premature deaths resulting from CRC that occurred nationwide
      from 2008 through 2010, or 7,690 deaths annually, would have been avoided if
      everyone had experienced the lowest death rates of the most educated whites. More
      premature deaths could be averted in southern states (60% to 70%) than in
      northern and western states (30% to 40%). Restricting the analyses to persons age
      50 to 64 years, for whom CRC screening is recommended, resulted in similar
      findings. CONCLUSION: The majority of premature deaths from CRC in southern
      states and half these deaths nationwide are due to racial/ethnic, socioeconomic,
      and geographic inequalities.

PMID- 25385726
TI  - Reply to D. Pouessel et al, J.B. Aragon-Ching, and B.A. Adesunloye.

PMID- 25385728
TI  - Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant
      chemotherapy in bladder cancer: ready for prime time?

PMID- 25385727
TI  - Randomized phase III trial of amrubicin versus topotecan as second-line treatment
      for patients with small-cell lung cancer.
AB  - PURPOSE: Amrubicin, a third-generation anthracycline and potent topoisomerase II
      inhibitor, showed promising activity in small-cell lung cancer (SCLC) in phase II
      trials. This phase III trial compared the safety and efficacy of amrubicin versus
      topotecan as second-line treatment for SCLC. PATIENTS AND METHODS: A total of 637
      patients with refractory or sensitive SCLC were randomly assigned at a ratio of
      2:1 to 21-day cycles of amrubicin 40 mg/m(2) intravenously (IV) on days 1 to 3 or
      topotecan 1.5 mg/m(2) IV on days 1 to 5. Primary end point was overall survival
      (OS); secondary end points included overall response rate (ORR), progression-free
      survival (PFS), and safety. RESULTS: Median OS was 7.5 months with amrubicin
      versus 7.8 months with topotecan (hazard ratio [HR], 0.880; P = .170); in
      refractory patients, median OS was 6.2 and 5.7 months, respectively (HR, 0.77; P
      = .047). Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan
      (HR, 0.802; P = .018). ORR was 31.1% with amrubicin and 16.9% with topotecan
      (odds ratio, 2.223; P < .001). Grade >= 3 treatment-emergent adverse events in
      the amrubicin and topotecan arms were: neutropenia (41% v 54%; P = .004),
      thrombocytopenia (21% v 54%; P < .001), anemia (16% v 31%; P < .001), infections
      (16% v 10%; P = .043), febrile neutropenia (10% v 3%; P = .003), and cardiac
      disorders (5% v 5%; P = .759); transfusion rates were 32% and 53% (P < .001),
      respectively. NQO1 polymorphisms did not influence safety outcomes. CONCLUSION:
      Amrubicin did not improve survival when compared with topotecan in the second
      line treatment of patients with SCLC. OS did not differ significantly between
      treatment groups, although an improvement in OS was noted in patients with
      refractory disease treated with amrubicin.

PMID- 25385730
TI  - Reply to D. Pouessel et al, J.B. Aragon-Ching, and B.A. Adesunloye.

PMID- 25385729
TI  - Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma
      benefit from intensified chemotherapy with ACVBP plus rituximab compared with
      CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de
      l'Adulte/lymphoma study association phase III trial LNH 03-2B.
AB  - PURPOSE: To determine whether any tumor biomarkers could account for the survival
      advantage observed in the LNH 03-2B trial among patients with diffuse large B
      cell lymphoma (DLBCL) and low-intermediate risk according to the International
      Prognostic Index when treated with dose-intensive rituximab, doxorubicin,
      cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) compared with
      standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R
      CHOP). PATIENTS AND METHODS: Using immunohistochemistry, expression of CD10,
      BCL6, MUM1, MYC, and BCL2 and coexpression of MYC/BCL2 were examined. The
      interaction effects between each biomarker and treatment arm on survival were
      studied in a restricted model and a full model incorporating clinical parameters.
      RESULTS: Among the 379 patients analyzed in the trial, 229 tumors were evaluable
      for germinal center B-cell-like (GCB)/non-GCB subclassification according to the
      Hans algorithm. Among all the biomarkers, only the interaction between the Hans
      algorithm and the treatment arm was significant for progression-free survival
      (PFS) and overall survival (OS) in univariable (PFS, P = .04; OS, P = .01) and
      multivariable (PFS, P = .03; OS, P = .01) analyses. Non-GCB tumors predicted
      worse PFS (hazard ratio [HR], 3.21; 95% CI, 1.29 to 8.00; P = .01) and OS (HR,
      6.09; 95% CI, 1.37 to 27.03; P = .02) among patients treated with R-CHOP compared
      with patients who received R-ACVBP, whereas there were no significant survival
      differences between these regimens among patients with GCB tumors. CONCLUSION:
      The survival benefit related to R-ACVBP over R-CHOP is at least partly linked to
      improved survival among patients with non-GCB DLBCL. Therefore, the Hans
      algorithm could be considered a theragnostic biomarker for selecting young
      patients with DLBCL who can benefit from an intensified R-ACVBP
      immunochemotherapy regimen.

PMID- 25385731
TI  - Human epidermal growth factor receptor 2 testing in primary breast cancer in the
      era of standardized testing: a Canadian prospective study.
AB  - PURPOSE: Therapies that target overexpression of human epidermal growth factor
      receptor 2 (HER2) rely on accurate and timely assessment of all patients with new
      diagnoses. This study examines HER2 testing of primary breast cancer tissue when
      performed with immunohistochemistry (IHC) and additional in situ hybridization
      (ISH) for negative cases (IHC 0/1+). The analysis focuses on the rate of false
      negative HER2 tests, defined as IHC 0/1+ with an ISH ratio >= 2.0, in eight
      pathology centers across Canada. PATIENTS AND METHODS: Whole sections of surgical
      resections or tissue microarrays (TMAs) from invasive breast carcinoma tissue
      were tested by both IHC and ISH using standardized local methods. Samples were
      scored by the local breast pathologist, and consecutive HER2-negative IHC results
      (IHC 0/1+) were compared with the corresponding fluorescence or silver ISH
      result. RESULTS: Overall, 711 surgical excisions of primary breast cancer were
      analyzed by IHC and ISH; HER2 and chromosome 17 centromere (CEP17) counts were
      available in all cases. The overall rate of false-negative samples was 0.84% (six
      of 711 samples). Interpretable IHC and ISH scores were available in 1,212 cases
      from TMAs, and the overall rate of false-negative cases was 1.6% (16 of 978
      cases). CONCLUSION: Our observation confirms that IHC is an adequate test to
      predict negative HER2 status in primary breast cancer in surgical excision
      specimens, even when different antibodies and IHC platforms are used. The study
      supports the American Society of Clinical Oncology/College of American
      Pathologists and Canadian testing algorithms of using IHC followed by ISH for
      equivocal cases.

PMID- 25385732
TI  - Era of comprehensive cancer genome analyses.

PMID- 25385733
TI  - Neoadjuvant phase II studies of modified methotrexate, vinblastine, doxorubicin,
      and cisplatin in muscle-invasive bladder cancer.

PMID- 25385734
TI  - Neoadjuvant chemotherapy for muscle-invasive bladder cancer: are we asking the
      right questions?

PMID- 25385735
TI  - Can urinary PCA3 supplement PSA in the early detection of prostate cancer?
AB  - PURPOSE: Given the limited sensitivity and specificity of prostate-specific
      antigen (PSA), its widespread use as a screening tool has raised concerns for the
      overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer.
      To improve early-detection biopsy decisions, the National Cancer Institute
      conducted a prospective validation trial to assess the diagnostic performance of
      the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate
      cancer among men screened with PSA. PATIENTS AND METHODS: In all, 859 men (mean
      age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between
      December 2009 and June 2011 were enrolled. The primary outcomes were to assess
      whether PCA3 could improve the positive predictive value (PPV) for an initial
      biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat
      biopsy (at a score < 20). RESULTS: For the detection of any cancer, PPV was 80%
      (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to
      93%) in the repeat biopsy group. The addition of PCA3 to individual risk
      estimation models (which included age, race/ethnicity, prior biopsy, PSA, and
      digital rectal examination) improved the stratification of cancer and of high
      grade cancer. CONCLUSION: These data independently support the role of PCA3 in
      reducing the burden of prostate biopsies among men undergoing a repeat prostate
      biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly
      increases the probability that an initial prostate biopsy will identify cancer.

PMID- 25385736
TI  - Author financial conflicts of interest, industry funding, and clinical practice
      guidelines for anticancer drugs.
AB  - PURPOSE: Clinical practice guidelines (CPGs) and consensus statements (CSs) are
      used to apply evidence-based medicine or expert recommendations to clinical
      practice. Here we explore author financial conflicts of interest (FCOIs), sources
      of guideline funding, and their relationship with endorsement of specific drugs.
      METHODS: An electronic search of MEDLINE was conducted to identify CPGs and CSs
      for common solid cancers published between January 2003 and October 2013. The
      search was restricted to articles evaluating systemic therapy. We extracted data
      on self-reported author FCOIs, funding sources, use of manuscript writers, and
      endorsement of specific drugs in the abstract of the article. RESULTS: Of 142
      articles evaluated, 64% were CPGs, and 36% were CSs. The proportion of articles
      reporting FCOIs improved from 11% in 2003 to 93% in 2013 (P for trend < .001).
      Only 45% of articles explicitly reported funding sources. Of these, 65% disclosed
      partial or full industry sponsorship. Use of manuscript writers was declared in
      13%, but many articles did not explicitly report the role of authors in the
      writing of the manuscript. Endorsement of specific drugs was significantly
      associated with author FCOIs (odds ratio [OR], 7.29; P = .001), but not with
      industry funding (OR, 0.95; P = .37). CONCLUSION: Reporting of FCOIs in CPGs and
      CSs has improved over time. Despite prevalent funding of guideline development by
      industry, such funding is not associated with endorsement of specific drugs.
      Author FCOIs are prevalent, and endorsement of a specific drug seems to be more
      common when authors have FCOIs with the pharmaceutical company marketing that
      drug.

PMID- 25385737
TI  - Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows
      hematologic and molecular remissions in patients with relapsed or refractory B
      precursor acute lymphoblastic leukemia.
AB  - PURPOSE: Patients with relapsed or refractory acute lymphoblastic leukemia (ALL)
      have a dismal prognosis. CD19 is homogenously expressed in B-precursor ALL and
      can be targeted by the investigational bispecific T cell-engager antibody
      blinatumomab. A phase II trial was performed to determine clinical activity in
      this patient cohort. PATIENTS AND METHODS: Thirty-six patients with relapsed or
      refractory B-precursor ALL were treated with blinatumomab in cycles of 4-week
      continuous infusion followed by a 2-week treatment-free interval in a single-arm
      study with a dose-finding stage and an extension stage. The primary end point was
      complete remission (CR) or CR with partial hematologic recovery (CRh). Major
      secondary end points included minimal residual disease (MRD) response, rate of
      allogeneic hematopoietic stem-cell transplantation (HSCT) realization, relapse
      free survival (RFS), overall survival (OS), and incidence of adverse events
      (AEs). RESULTS: Median age was 32 years (range, 18 to 77 years). Twenty-five
      patients (69%) achieved a CR or CRh, with 88% of the responders achieving an MRD
      response. Median OS was 9.8 months (95% CI, 8.5 to 14.9), and median RFS was 7.6
      months (95% CI, 4.5 to 9.5). Thirteen responders (52%) underwent HSCT after
      achieving a CR or CRh. The most frequent AE during treatment was pyrexia (grade 1
      or 2, 75%; grade 3, 6%). In six patients with nervous system or psychiatric
      disorder AEs and in two patients with cytokine release syndrome, treatment had to
      be interrupted or discontinued. These medical events were resolved clinically.
      CONCLUSION: The data support further investigation of blinatumomab for the
      treatment of adult patients with relapsed or refractory ALL in a larger
      confirmatory study.

PMID- 25385738
TI  - Evaluation of 30-day hospital readmission after surgery for advanced-stage
      ovarian cancer in a medicare population.
AB  - PURPOSE: To analyze rate, risk factors, and costs associated with 30-day
      readmission after ovarian cancer surgery. PATIENTS AND METHODS: The SEER-Medicare
      linked database (1992 to 2010) was used to evaluate readmission rates within 30
      days of index surgery in patients with stage IIIC/IV ovarian, primary peritoneal,
      or fallopian tube cancer. Multivariable logistic regression was used to identify
      factors associated with readmission. RESULTS: Of 5,152 eligible patients, 1,003
      (19.5%) were readmitted within 30 days of discharge. Mean patient age was 75
      years. Diagnoses associated with readmission included infection (34.7%),
      dehydration (34.3%), ileus/obstruction (26.2%), metabolic/electrolyte
      derangements (23.1%), and anemia (12.3%). In multivariable analysis, year of
      discharge was significantly associated with 30-day readmission (1996 to 2000:
      odds ratio [OR], 1.32; 95% CI, 1.01 to 1.71; 2001 to 2005: OR, 1.58; 95% CI, 1.24
      to 2.0; 2006 to 2010: OR, 1.73; 95% CI, 1.35 to 2.21; referent years 1992 to
      1995), as were length of index hospital stay more than 8 days (OR, 1.39; 95% CI,
      1.18 to 1.64) and discharge to a skilled nursing facility (OR, 1.3; 95% CI, 1.04
      to 1.63). Patients readmitted within 30 days had a significantly greater 1-year
      mortality rate compared with patients not readmitted (41.1% v 25.1%,
      respectively; P < .001). The median cost of readmission hospital stay was $9,220
      in year 2010 dollars, with a total cost of $9.3 million over the study period.
      CONCLUSION: Early readmission after surgery for ovarian cancer is common. There
      is a significant association between 30-day readmission and 1-year mortality.
      These findings may catalyze development of targeted interventions to decrease
      early readmission, improve patient outcomes, and control health care costs.

PMID- 25385739
TI  - Identification of independent primary tumors and intrapulmonary metastases using
      DNA rearrangements in non-small-cell lung cancer.
AB  - PURPOSE: Distinguishing independent primary tumors from intrapulmonary metastases
      in non-small-cell carcinoma remains a clinical dilemma with significant clinical
      implications. Using next-generation DNA sequencing, we developed a chromosomal
      rearrangement-based approach to differentiate multiple primary tumors from
      metastasis. METHODS: Tumor specimens from patients with known independent primary
      tumors and metastatic lesions were used for lineage test development, which was
      then applied to multifocal tumors. Laser capture microdissection was performed
      separately for each tumor. Genomic DNA was isolated using direct in situ whole
      genome amplification methodology, and next-generation sequencing was performed
      using an Illumina mate-pair library protocol. Sequence reads were mapped to the
      human genome, and primers spanning the fusion junctions were used for validation
      polymerase chain reaction. RESULTS: A total of 41 tumor samples were sequenced
      (33 adenocarcinomas [ADs] and eight squamous cell carcinomas [SQCCs]), with a
      range of three to 276 breakpoints per tumor identified. Lung tumors predicted to
      be independent primary tumors based on different histologic subtype did not share
      any genomic rearrangements. In patients with lung primary tumors and paired
      distant metastases, shared rearrangements were identified in all tumor pairs,
      emphasizing the patient specificity of identified breakpoints. Multifocal AD and
      SQCC samples were reviewed independently by two pulmonary pathologists.
      Concordance between histology and genomic data occurred in the majority of
      samples. Discrepant tumor samples were resolved by genome sequencing. CONCLUSION:
      A diagnostic lineage test based on genomic rearrangements from mate-pair
      sequencing demonstrates promise for distinguishing independent primary from
      metastatic disease in lung cancer.

PMID- 25385740
TI  - Cigarette smoking prior to first cancer and risk of second smoking-associated
      cancers among survivors of bladder, kidney, head and neck, and stage I lung
      cancers.
AB  - PURPOSE: Data on smoking and second cancer risk among cancer survivors are
      limited. We assessed associations between smoking before first cancer diagnosis
      and risk of second primary smoking-associated cancers among survivors of lung
      (stage I), bladder, kidney, and head/neck cancers. METHODS: Data were pooled from
      2,552 patients with stage I lung cancer, 6,386 with bladder cancer, 3,179 with
      kidney cancer, and 2,967 with head/neck cancer from five cohort studies. We
      assessed the association between prediagnostic smoking and second smoking
      associated cancer risk with proportional hazards regression, and compared these
      estimates to those for first smoking-associated cancers in all cohort
      participants. RESULTS: Compared with never smoking, current smoking of >= 20
      cigarettes per day was associated with increased second smoking-associated cancer
      risk among survivors of stage I lung (hazard ratio [HR] = 3.26; 95% CI, 0.92 to
      11.6), bladder (HR = 3.67; 95% CI, 2.25 to 5.99), head/neck (HR = 4.45; 95% CI,
      2.56 to 7.73), and kidney cancers (HR = 5.33; 95% CI, 2.55 to 11.1). These
      estimates were similar to those for first smoking-associated cancer among all
      cohort participants (HR = 5.41; 95% CI, 5.23 to 5.61). The 5-year cumulative
      incidence of second smoking-associated cancers ranged from 3% to 8% in this group
      of cancer survivors. CONCLUSION: Understanding risk factors for second cancers
      among cancer survivors is crucial. Our data indicate that cigarette smoking
      before first cancer diagnosis increases second cancer risk among cancer
      survivors, and elevated cancer risk in these survivors is likely due to increased
      smoking prevalence. The high 5-year cumulative risks of smoking-associated
      cancers among current smoking survivors of stage I lung, bladder, kidney, and
      head/neck cancers highlight the importance of smoking cessation in patients with
      cancer.

PMID- 25385742
TI  - Time to diagnosis of ewing tumors in children and adolescents is not associated
      with metastasis or survival.

PMID- 25385743
TI  - Margaret McCartney: Fat doctors are patients too.

PMID- 25385741
TI  - Individual patient data analysis of progression-free survival versus overall
      survival as a first-line end point for metastatic colorectal cancer in modern
      randomized trials: findings from the analysis and research in cancers of the
      digestive system database.
AB  - PURPOSE: Progression-free survival (PFS) has previously been established as a
      surrogate for overall survival (OS) for first-line metastatic colorectal cancer
      (mCRC). Because mCRC treatment has advanced in the last decade with extended OS,
      this surrogacy requires re-examination. METHODS: Individual patient data from
      16,762 patients were available from 22 first-line mCRC studies conducted from
      1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal
      growth factor receptor agents. The relationship between PFS (first event of
      progression or death) and OS was evaluated by using R(2) statistics (the closer
      the value is to 1, the stronger the correlation) from weighted least squares
      regression of trial-specific hazard ratios estimated by using Cox and Copula
      models. RESULTS: Forty-four percent of patients received a regimen that included
      biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2
      months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69).
      Analyses limited to trials that tested treatments with biologic agents,
      nonstrategy trials, or superiority trials did not improve surrogacy. CONCLUSION:
      In modern mCRC trials, in which survival after the first progression exceeds time
      to first progression, a positive but modest correlation was observed between OS
      and PFS at both the patient and trial levels. This finding demonstrates the
      substantial variability in OS introduced by the number of lines of therapy and
      types of effective subsequent treatments and the associated challenge to the use
      of OS as an end point to assess the benefit attributable to a single line of
      therapy. PFS remains an appropriate primary end point for first-line mCRC trials
      to detect the direct treatment effect of new agents.

PMID- 25385744
TI  - Prevalence of chronic endometritis in repeated unexplained implantation failure
      and the IVF success rate after antibiotic therapy.
AB  - STUDY QUESTION: What is the prevalence of chronic endometritis (CE) in women with
      repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic
      treatment affect the reproductive outcome? SUMMARY ANSWER: Chronic endometritis,
      associated with infection with common bacteria or mycoplasma, is common in women
      complaining of RIF and antibiotic treatment significantly improves the
      reproductive outcome at a subsequent IVF cycle. WHAT IS KNOWN ALREADY: We have
      reported that CE is a frequent finding in women with repeated pregnancy loss and
      a significantly higher rate of successful pregnancies was achieved after adequate
      antibiotic treatment. Moreover, CE was identified in 30.3% of patients with
      repeated implantation failure at IVF and women diagnosed with CE had lower
      implantation rates (11.5%) after IVF cycles. In contrast, other authors reported
      that the clinical implication of CE should be considered minimal and that the
      reproductive outcome at IVF/ICSI cycles was not negatively affected by CE. STUDY
      DESIGN, SIZE, DURATION: A retrospective study was performed from January 2009
      through June 2012 on 106 women with unexplained infertility and a history of RIF.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent hysteroscopy and
      endometrial sampling for histology and microbiological investigations. Women
      diagnosed with CE underwent antibiotic treatment and the effect of treatment was
      confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women
      had a further IVF attempt. The IVF outcomes were compared in women without signs
      of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical
      pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment
      IVF attempt. MAIN RESULTS AND THE ROLE OF CHANCE: Seventy (66.0%) women were
      diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology
      and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most
      prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at
      hysteroscopy and histology, examinations were normal after appropriate antibiotic
      treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still
      present (Group 2). At IVF attempt after treatment, a significantly higher PR and
      LBR was reported in women from Group 1 compared with women from Group 2 (65.2
      versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively). LIMITATIONS,
      REASONS FOR CAUTION: Possible biases related to retrospective studies and to
      preferential referral of patients with CE, and limited number of cases. WIDER
      IMPLICATIONS OF THE FINDINGS: A prospective randomized clinical trial is needed
      to confirm our findings but in women with RIF a hysteroscopic evaluation of the
      uterine cavity to exclude CE should be considered and appropriate antibiotic
      treatment should be given before submitting the patient to a further IVF attempt.

PMID- 25385745
TI  - Depression, adherence and attrition from care in HIV-infected adults receiving
      antiretroviral therapy.
AB  - BACKGROUND: A better understanding of the relationship between depression and HIV
      related outcomes, particularly as it relates to adherence to treatment, is
      critical to guide effective support and treatment of individuals with HIV and
      depression. We examined whether depression was associated with attrition from
      care in a cohort of 610 HIV-infected adults in rural Rwanda and whether this
      relationship was mediated through suboptimal adherence to treatment. METHODS: The
      association between depression and attrition from care was evaluated with a Cox
      proportional hazard model and with mediation methods that calculate the direct
      and indirect effects of depression on attrition and are able to account for
      interactions between depression and suboptimal adherence. Depression was assessed
      with the Hopkins Symptom Checklist-15; attrition was defined as death, treatment
      default, or loss to follow-up. RESULTS: Baseline depression was significantly
      associated with time to attrition after adjustment for receipt of community-based
      accompaniment, physical functioning quality of life score, and CD4 cell count
      (HR=2.40, 95% CI 1.27 to 4.52, p=0.005). In multivariable mediation analysis, we
      found no evidence that the association between depression and attrition after 3
      months was mediated by suboptimal adherence (direct effect of depression on
      attrition: OR=3.90 (1.26 to 12.04), p=0.02; indirect effect: OR=1.07 (0.92 to
      1.25), p=0.38). CONCLUSIONS: Even in the context of high antiretroviral therapy
      adherence, depression may adversely influence HIV outcomes through a pathway
      other than suboptimal adherence. Treatment of depression is critical to achieving
      good mental health and retention in HIV-infected individuals with depression.

PMID- 25385746
TI  - Effect of antiplatelet therapy and platelet function testing on hemorrhagic and
      thrombotic complications in patients with cerebral aneurysms treated with the
      pipeline embolization device: a review and meta-analysis.
AB  - PURPOSE: The pipeline embolization device (PED) necessitates dual antiplatelet
      therapy (APT) to decrease thrombotic complications while possibly increasing
      bleeding risks. The role of APT dose, duration, and response in patients with
      hemorrhagic and thromboembolic events warrants further analysis. METHODS: A
      PubMed and Google Scholar search from 2009 to 2014 was performed using the
      following search terms individually or in combination: pipeline embolization
      device, aneurysm(s), and flow diversion, excluding other flow diverters. Review
      of the bibliographies of the retrieved articles yielded 19 single and multicenter
      studies. A statistical meta-analysis between aspirin (ASA) dose (low dose <=160
      mg, high dose >=300 mg), loading doses of APT agents, post-PED APT regimens, and
      platelet function testing (PFT) with hemorrhagic or thrombotic complications was
      performed. RESULTS: ASA therapy for <=6 months post-PED was associated with
      increased hemorrhagic events. High dose ASA <=6 months post-PED was associated
      with fewer thrombotic events compared with low dose ASA. Post-PED clopidogrel for
      <=6 months demonstrated an increased incidence of symptomatic thrombotic events.
      Loading doses of ASA plus clopidogrel demonstrated a decreased incidence of
      permanent symptomatic hemorrhagic events. PFT did not show a statistically
      significant relationship with symptomatic hemorrhagic or thrombotic
      complications. CONCLUSIONS: High dose ASA >6 months is associated with fewer
      permanent thrombotic and hemorrhagic events. Clopidogrel therapy <=6 months is
      associated with higher rates of thrombotic events. Loading doses of ASA and
      clopidogrel were associated with a decreased incidence of hemorrhagic events. PFT
      did not have any significant association with symptomatic events.

PMID- 25385747
TI  - Interobserver variability of aneurysm morphology: discrimination of the daughter
      sac.
AB  - OBJECTIVE: Several definitions have been proposed to distinguish the daughter sac
      when treating unruptured intracranial aneurysms. The aim of this study was to
      evaluate interobserver variability of aneurysm morphology, including the daughter
      sac, using criteria from the International Study of Unruptured Intracranial
      Aneurysms (ISUIA) and the Unruptured Cerebral Aneurysm Study of Japan (UCAS).
      MATERIALS AND METHODS: After approval by the institutional review board, we
      analyzed three morphological features (daughter sac, lobulation, and irregular
      margin) from the ISUIA and UCAS using angiographic images from 102 saccular
      aneurysms. Four independent readers interpreted each morphological criterion
      using dichotomized scales (existence or not). The kappa statistic was used to
      measure interobserver agreement, and kappa>0.6 was considered substantial
      agreement. RESULTS: For discrimination of the daughter sac, interobserver
      agreement among the four readers was substantial using the UCAS criteria (k=0.626
      for two-dimensional (2D) and 0.659 for three-dimensional (3D) images) but not for
      the ISUIA criteria (k=0.487 for 2D and 0.473 for 3D images; significant
      difference). Irrespective of the images used, pairwise pooled kappa values for
      the UCAS were >0.6, except for one case (score of 0.54 between readers A and B).
      Regarding the proportion of positive reads, there was a significant difference
      between reads for the daughter sac using the UCAS and ISUIA criteria.
      CONCLUSIONS: For discrimination of the daughter sac, the UCAS definition showed a
      higher reliability than the ISUIA. However, a further prospective study is
      necessary to validate this definition as the treatment standard for unruptured
      intracranial aneurysms.

PMID- 25385748
TI  - Thinking about the burden of treatment.

PMID- 25385749
TI  - Comparison of general population, patient, and carer utility values for dementia
      health states.
AB  - Utility values to estimate quality-adjusted life years (QALYs) for use in cost
      utility analyses are usually elicited from members of the general population.
      Public attitudes and understanding of dementia in particular may mean that values
      elicited from the general population may differ from patients and carers for
      dementia health states. This study examines how the population impacts utility
      values elicited for dementia health states using interviewer-administered time
      tradeoff valuation of health states defined by the dementia-specific preference
      based measures DEMQOL-U (patient-report) and DEMQOL-Proxy-U (carer-report). Eight
      DEMQOL-U states were valued by 78 members of the UK general population and 71
      patients with dementia of mild severity. Eight DEMQOL-Proxy-U states were valued
      by 77 members of the UK general population and 71 carers of patients with
      dementia of mild severity. Random-effects generalized least squares regression
      estimated the impact of population, dementia health state, and respondent
      sociodemographic characteristics on elicited values, finding that values for
      dementia health states differed by population and that the difference varied
      across dementia health states. Patients with dementia and carers of patients with
      dementia gave systematically lower values than members of the general population
      that were not due to differences in the sociodemographic characteristics of the
      populations. Our results suggest that the population used to produce dementia
      health state values could impact the results of cost-utility analyses and
      potentially affect resource allocation decisions; yet, currently, only general
      population values are available for usage.

PMID- 25385750
TI  - Improving Geographic Equity in Kidney Transplantation Using Alternative Kidney
      Sharing and Optimization Modeling.
AB  - The national demand for kidney transplantation far outweighs the supply of kidney
      organs. Currently, a patient's ability to receive a kidney transplant varies
      depending on where he or she seeks transplantation. This reality is in direct
      conflict with a federal mandate from the Department of Health and Human Services.
      We analyze current kidney allocation and develop an alternative kidney sharing
      strategy using a multiperiod linear optimization model, KSHARE. KSHARE aims to
      improve geographic equity in kidney transplantation while also respecting
      transplant system constraints and priorities. KSHARE is tested against actual
      2000-2009 kidney allocation using Organ Procurement and Transplant Network data.
      Geographic equity is represented by minimizing the range in kidney transplant
      rates around local areas of the country. In 2009, less than 25% of standard
      criteria donor kidneys were allocated beyond the local area of procurement, and
      Donor Service Area kidney transplantation rates varied from 3.0% to 30.0%, for an
      overall range of 27.0%. Given optimal sharing of kidneys within 600 miles of
      procurement for 2000-2009, kidney transplant rates vary from 5.0% to 12.5% around
      the country for an overall kidney transplant range of 7.5%. Nationally sharing
      kidneys optimally between local areas only further decreases the transplant rate
      range by 1.7%. Enhancing the practice of sharing kidneys by the KSHARE model may
      increase geographic equity in kidney transplantation.

PMID- 25385752
TI  - Joint reproductive autonomy: does Evans v Amicus Healthcare Ltd provide for a
      gender-neutral approach to assisted reproductive rights?
AB  - Assisted reproductive technology encompasses methods of achieving pregnancy by
      artificial or partially artificial means. Whilst these methods are more commonly
      used by couples suffering from problems of infertility, some forms of assistance
      are employed by fertile couples, for example pre-implantation genetic diagnosis.
      The overall regulatory framework in the UK is predominantly found in the Human
      Fertilisation and Embryology Act 1990. The usual rules relating to consent and
      autonomy apply and were discussed in depth in Evans v Amicus Healthcare Ltd and
      later in Evans v United Kingdom. This paper considers whether the Evans
      litigation envisages the possibility of further encouraging joint autonomy in the
      use of zygotes and whether there is a continuing right to autonomy by the party
      not bearing the pregnancy. 

PMID- 25385751
TI  - Decision-making Processes among Prostate Cancer Survivors with Rising PSA Levels:
      Results from a Qualitative Analysis.
AB  - BACKGROUND: Prostate cancer survivors with a rising prostate-specific antigen
      (PSA) level have few treatment options, experience a heightened state of
      uncertainty about their disease trajectory that might include the possibility of
      cancer metastasis and death, and often experience elevated levels of distress as
      they have to deal with a disease they thought they had conquered. Guided by self
      regulation theory, the present study examined the cognitive and affective
      processes involved in shared decision making between physicians and patients who
      experience a rising PSA after definitive treatment for prostate cancer. METHODS:
      In-depth interviews were conducted with 34 prostate cancer survivors who had been
      diagnosed with a rising PSA (i.e., biochemical failure) within the past 12
      months. Survivors were asked about their experiences and affective responses
      after being diagnosed with a rising PSA and while weighing potential treatment
      options. In addition, patients were asked about their decision-making process for
      the initial prostate cancer treatment. RESULTS: Compared with the initial
      diagnosis, survivors with a rising PSA reported increased negative affect
      following their diagnosis, concern about the treatability of their disease,
      increased planning and health behavior change, heightened levels of worry
      preceding doctor appointments (especially prior to the discussion of PSA testing
      results), and a strong reliance on physicians' treatment recommendations.
      CONCLUSIONS: Prostate cancer survivors' decision-making processes for the
      treatment of a rising PSA are markedly different from those of the initial
      diagnosis of prostate cancer. Because patients experience heightened distress and
      rely more heavily on their physicians' recommendations with a rising PSA,
      interactions with the health care provider provide an excellent opportunity to
      address and assist patients with managing the uncertainty and distress inherent
      with rising PSA levels.

PMID- 25385753
TI  - Variation between residents and attending staff interpreting radiographs to
      verify placement of nutrition access devices in the neonatal intensive care unit.
AB  - INTRODUCTION: Although radiography is considered the standard for confirming the
      position of nutrition access devices, it is sometimes difficult to visualize
      their tips. The purpose of this study was to evaluate how well pediatric
      residents could confirm placement via radiography of feeding tubes and
      intravenous (IV) nutrition catheter support in a neonatal intensive care unit
      (NICU). METHODS: Seventy radiographs in a NICU during May 2013 were
      retrospectively evaluated. Eight pediatric residents (mean NICU experience, 5
      months; range, 0-12 months) recorded the location of feeding tubes and IV
      nutrition catheters and marked their tips on computerized radiographs. Consensus
      review of radiographs by a radiologist and a NICU expert using a picture
      archiving communication system monitor in a reading room served as the reference
      standard. Detection rates and correct tip localization percentages were
      evaluated. RESULTS: Of the 70 neonates, 38 had nutrition access devices:
      orogastric tube (n = 36), oroduodenal tube (n = 4), or central venous catheter
      (CVC) (n = 8). Detection rates were 89.6% for orogastric tubes (range, 75.0%
      100%), 90.6% for oroduodenal tubes (range, 50.0%-100%), and 46.9% for CVCs
      (range, 12.5%-75.0%). Percentage of correct tip localizations was 85.7% for
      orogastric tubes (range, 74.1%-100%), 86.2% for oroduodenal tubes (range, 25.0%
      100%), and 70% for CVCs (range, 50.0%-100%). CONCLUSION: It is not easy for
      pediatrician residents to confirm the position of nutrition access devices in
      neonates by using radiographs. Reinforcement of radiology teaching, second
      opinions from radiologists or NICU experts, and other methods for verifying the
      positions of nutrition access devices are needed to minimize complications.

PMID- 25385754
TI  - An inherited mutation in NLRC4 causes autoinflammation in human and mice.
AB  - Autoinflammatory syndromes cause sterile inflammation in the absence of any signs
      of autoimmune responses. Familial cold autoinflammatory syndrome (FCAS) is
      characterized by intermittent episodes of rash, arthralgia, and fever after
      exposure to cold stimuli. We have identified a missense mutation in the NLRC4
      gene in patients with FCAS. NLRC4 has been known as a crucial sensor for several
      Gram-negative intracellular bacteria. The mutation in NLRC4 in FCAS patients
      promoted the formation of NLRC4-containing inflammasomes that cleave procaspase-1
      and increase production of IL-1beta. Transgenic mice that expressed mutant Nlrc4
      under the invariant chain promoter developed dermatitis and arthritis.
      Inflammation within tissues depended on IL-1beta-mediated production of IL-17A
      from neutrophils but not from T cells. Our findings reveal a previously
      unrecognized link between NLRC4 and a hereditary autoinflammatory disease and
      highlight the importance of NLRC4 not only in the innate immune response to
      bacterial infections but also in the genesis of inflammatory diseases. 

PMID- 25385755
TI  - Identification of Cdca7 as a novel Notch transcriptional target involved in
      hematopoietic stem cell emergence.
AB  - Hematopoietic stem cell (HSC) specification occurs in the embryonic aorta and
      requires Notch activation; however, most of the Notch-regulated elements
      controlling de novo HSC generation are still unknown. Here, we identify putative
      direct Notch targets in the aorta-gonad-mesonephros (AGM) embryonic tissue by
      chromatin precipitation using antibodies against the Notch partner RBPj. By ChIP
      on-chip analysis of the precipitated DNA, we identified 701 promoter regions that
      were candidates to be regulated by Notch in the AGM. One of the most enriched
      regions corresponded to the Cdca7 gene, which was subsequently confirmed to
      recruit the RBPj factor but also Notch1 in AGM cells. We found that during
      embryonic hematopoietic development, expression of Cdca7 is restricted to the
      hematopoietic clusters of the aorta, and it is strongly up-regulated in the
      hemogenic population during human embryonic stem cell hematopoietic
      differentiation in a Notch-dependent manner. Down-regulation of Cdca7 mRNA in
      cultured AGM cells significantly induces hematopoietic differentiation and loss
      of the progenitor population. Finally, using loss-of-function experiments in
      zebrafish, we demonstrate that CDCA7 contributes to HSC emergence in vivo during
      embryonic development. Thus, our study identifies Cdca7 as an evolutionary
      conserved Notch target involved in HSC emergence. 

PMID- 25385756
TI  - Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus
      escape variants.
AB  - Antibody-mediated immunotherapy is effective in humanized mice when combinations
      of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping
      sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast,
      single bNAbs can control simian-human immunodeficiency virus (SHIV) infection in
      immune-competent macaques, suggesting that the host immune response might also
      contribute to the control of viremia. Here, we investigate how the autologous
      antibody response in intact hosts can contribute to the success of immunotherapy.
      We find that frequently arising antibodies that normally fail to control HIV-1
      infection can synergize with passively administered bNAbs by preventing the
      emergence of bNAb viral escape variants. 

PMID- 25385758
TI  - Burden of undiagnosed hypertension in sub-saharan Africa: a systematic review and
      meta-analysis.
AB  - The burden of hypertension in Sub-Saharan Africa has been increasing over the
      past few decades. However, a large proportion of the population with hypertension
      remains undiagnosed, untreated, or inadequately treated, contributing to the
      rising burden of cardiovascular disease in the region. We conducted a systematic
      review and meta-analysis to assess the recent burden of hypertension in Sub
      Saharan Africa, based on studies published between 2000 and 2013. We pooled data
      from 33 surveys involving over 110 414 participants of mean age 40 years.
      Hypertension prevalence varied widely across the studies (range 15%-70%), partly
      because of differences in participant mean ages (31-76 years). The predicted
      prevalence of hypertension at mean participant ages of 30, 40, 50, and 60 years
      were 16%, 26%, 35%, and 44%, respectively, with a pooled prevalence of 30% (95%
      confidence interval, 27%-34%). Of those with hypertension, only between 7% and
      56% (pooled prevalence: 27%; 95% confidence interval, 23%-31%) were aware of
      their hypertensive status before the surveys. Overall, 18% (95% confidence
      interval, 14%-22%) of individuals with hypertension were receiving treatment
      across the studies, and only 7% (95% confidence interval, 5%-8%) had controlled
      blood pressure. This review found a high prevalence of hypertension, as well as
      low percentage of hypertension awareness, treatment, and control in Sub-Saharan
      Africa, highlighting the need for implementation of timely and appropriate
      strategies for diagnosis, control, and prevention. 

PMID- 25385757
TI  - Limitation of immune tolerance-inducing thymic epithelial cell development by Spi
      B-mediated negative feedback regulation.
AB  - Medullary thymic epithelial cells (mTECs) expressing the autoimmune regulator
      AIRE and various tissue-specific antigens (TSAs) are critical for preventing the
      onset of autoimmunity and may attenuate tumor immunity. However, molecular
      mechanisms controlling mTEC development remain elusive. Here, we describe the
      roles of the transcription factor Spi-B in mTEC development. Spi-B is rapidly up
      regulated by receptor activator of NF-kappaB ligand (RANKL) cytokine signaling,
      which triggers mTEC differentiation, and in turn up-regulates CD80, CD86, some
      TSAs, and the natural inhibitor of RANKL signaling, osteoprotegerin (OPG). Spi-B
      mediated OPG expression limits mTEC development in neonates but not in embryos,
      suggesting developmental stage-specific negative feedback regulation. OPG
      mediated negative regulation attenuates cellularity of thymic regulatory T cells
      and tumor development in vivo. Hence, these data suggest that this negative RANKL
      Spi-B-OPG feedback mechanism finely tunes mTEC development and function and may
      optimize the trade-off between prevention of autoimmunity and induction of
      antitumor immunity. 

PMID- 25385759
TI  - NO for the pregnant mother: no hypertension for the daughter?

PMID- 25385760
TI  - Maternal treatment of spontaneously hypertensive rats with pentaerythritol
      tetranitrate reduces blood pressure in female offspring.
AB  - Pentaerythritol tetranitrate is devoid of nitrate tolerance and shows no
      reproductive or developmental toxicity in animal studies. Recently,
      pentaerythritol tetranitrate has been demonstrated to reduce the risk of
      intrauterine growth restriction and the risk of preterm birth in women with
      abnormal placental perfusion. This study was conducted to test the perinatal
      programming effect of pentaerythritol tetranitrate in spontaneously hypertensive
      rats, a rat model of genetic hypertension. Parental spontaneously hypertensive
      rats were treated with pentaerythritol tetranitrate (50 mg/kg per day) during
      pregnancy and lactation periods; the offspring received standard chow without
      pentaerythritol tetranitrate after weaning. Maternal treatment with
      pentaerythritol tetranitrate had no effect on blood pressure in male offspring.
      In the female offspring, however, a persistent reduction in blood pressure was
      observed at 6 and 8 months. This long-lasting effect was accompanied by an
      upregulation of endothelial nitric oxide synthase, mitochondrial superoxide
      dismutase, glutathione peroxidase 1, and heme oxygenase 1 in the aorta of 8-month
      old female offspring, which was likely to result from epigenetic changes
      (enhanced histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation)
      and transcriptional activation (enhanced binding of DNA-directed RNA polymerase
      II to the transcription start site of the genes). In organ chamber experiments,
      the endothelium-dependent, nitric oxide-mediated vasodilation to acetylcholine
      was enhanced in aorta from female offspring of the pentaerythritol tetranitrate
      treated parental spontaneously hypertensive rats. In conclusion, maternal
      pentaerythritol tetranitrate treatment leads to epigenetic modifications, gene
      expression changes, an improvement of endothelial function and a persistent blood
      pressure reduction in the female offspring. 

PMID- 25385761
TI  - Genome-wide identification of long noncoding RNAs in rat models of cardiovascular
      and renal disease.
AB  - Long noncoding RNAs (lncRNAs) are an emerging class of genomic regulatory
      molecules reported in various species. In the rat, which is one of the major
      mammalian model organisms, discovery of lncRNAs on a genome-wide scale is
      lagging. Renal lncRNA sequencing and lncRNA transcriptome analysis were conducted
      in 3 rat strains that are widely used in cardiovascular and renal research: the
      Dahl salt-sensitive rat, the spontaneously hypertensive rat, and the Dahl salt
      resistant rat. Through the RNA sequencing approach, 3273 transcripts were
      identified as rat lncRNAs. A majority of lncRNAs were without predicted target
      genes. Differential expression of 273 and 749 lncRNAs was detected between Dahl
      salt-sensitive versus Dahl salt-resistant and Dahl salt-sensitive versus
      spontaneously hypertensive rat comparisons, respectively. To couple the observed
      differential expression of lncRNAs with the status of mRNAs, an mRNA
      transcriptome analysis was conducted. Several cis mRNA genes were coregulated
      with lncRNAs. Of these, the protein expression status of 4 target genes, Asb3,
      Chac2, Pex11b, and Sp5, were differentially expressed between the relevant strain
      comparisons, thereby suggesting that the differentially expressed lncRNAs
      associated with these genes are candidate genetic determinants of blood pressure.
      This study serves as a first-generation catalog of rat lncRNAs and illustrates
      the prioritization of lncRNAs as candidates for complex polygenic traits. 

PMID- 25385763
TI  - Rare cause of severe hypertension in a young woman.

PMID- 25385762
TI  - Genetic interference with peroxisome proliferator-activated receptor gamma in
      smooth muscle enhances myogenic tone in the cerebrovasculature via A Rho kinase
      dependent mechanism.
AB  - Myogenic responses by resistance vessels are a key component of autoregulation in
      brain, thus playing a crucial role in regulating cerebral blood flow and
      protecting the blood-brain barrier against potentially detrimental elevations in
      blood pressure. Although cerebrovascular disease is often accompanied by
      alterations in myogenic responses, mechanisms that control these changes are
      poorly understood. Peroxisome proliferator-activated receptor gamma has emerged
      as a regulator of vascular tone. We hypothesized that interference with
      peroxisome proliferator-activated receptor gamma in smooth muscle would augment
      myogenic responses in cerebral arteries. We studied transgenic mice expressing a
      dominant-negative mutation in peroxisome proliferator-activated receptor gamma
      selectively in smooth muscle (S-P467L) and nontransgenic littermates. Myogenic
      tone in middle cerebral arteries from S-P467L was elevated 3-fold when compared
      with nontransgenic littermates. Rho kinase is thought to play a major role in
      cerebrovascular disease. The Rho kinase inhibitor, Y-27632, abolished augmented
      myogenic tone in middle cerebral arteries from S-P467L mice. CN-03, which
      modifies RhoA making it constitutively active, elevated myogenic tone to ~60% in
      both strains, via a Y-27632-dependent mechanism. Large conductance Ca(2+)
      activated K(+) channels (BKCa) modulate myogenic tone. Inhibitors of BKCa caused
      greater constriction in middle cerebral arteries from nontransgenic littermates
      when compared with S-P467L. Expression of RhoA or Rho kinase-I/II protein was
      similar in cerebral arteries from S-P467L mice. Overall, the data suggest that
      peroxisome proliferator-activated receptor gamma in smooth muscle normally
      inhibits Rho kinase and promotes BKCa function, thus influencing myogenic tone in
      resistance arteries in brain. These findings have implications for mechanisms
      that underlie large- and small-vessel disease in brain, as well as regulation of
      cerebral blood flow. 

PMID- 25385764
TI  - Paretic Propulsion and Trailing Limb Angle Are Key Determinants of Long-Distance
      Walking Function After Stroke.
AB  - BACKGROUND: Elucidation of the relative importance of commonly targeted
      biomechanical variables to poststroke long-distance walking function would
      facilitate optimal intervention design. OBJECTIVES: To determine the relative
      contribution of variables from 3 biomechanical constructs to poststroke long
      distance walking function and identify the biomechanical changes underlying
      posttraining improvements in long-distance walking function. METHODS: Forty-four
      individuals >6 months after stroke participated in this study. A subset of these
      subjects (n = 31) underwent 12 weeks of high-intensity locomotor training. Cross
      sectional (pretraining) and longitudinal (posttraining change) regression
      quantified the relationships between poststroke long-distance walking function,
      as measured via the 6-Minute Walk Test (6MWT), and walking biomechanics.
      Biomechanical variables were organized into stance phase (paretic propulsion and
      trailing limb angle), swing phase (paretic ankle dorsiflexion and knee flexion),
      and symmetry (step length and swing time) constructs. RESULTS: Pretraining, all
      variables correlated with 6MWT distance (rs = .39 to .75, Ps < .05); however,
      only propulsion (Prop) and trailing limb angle (TLA) independently predicted 6MWT
      distance, R(2) = .655, F(6, 36) = 11.38, P < .001. Interestingly, only DeltaProp
      predicted Delta6MWT; however, pretraining Prop, pretraining TLA, and DeltaTLA
      moderated this relationship (moderation model R(2)s = .383, .468, .289,
      respectively). CONCLUSIONS: The paretic limb's ability to generate propulsion
      during walking is a critical determinant of long-distance walking function after
      stroke. This finding supports the development of poststroke interventions that
      target deficits in propulsion and trailing limb angle.

PMID- 25385765
TI  - Neural Point-and-Click Communication by a Person With Incomplete Locked-In
      Syndrome.
AB  - A goal of brain-computer interface research is to develop fast and reliable means
      of communication for individuals with paralysis and anarthria. We evaluated the
      ability of an individual with incomplete locked-in syndrome enrolled in the
      BrainGate Neural Interface System pilot clinical trial to communicate using
      neural point-and-click control. A general-purpose interface was developed to
      provide control of a computer cursor in tandem with one of two on-screen virtual
      keyboards. The novel BrainGate Radial Keyboard was compared to a standard QWERTY
      keyboard in a balanced copy-spelling task. The Radial Keyboard yielded a
      significant improvement in typing accuracy and speed-enabling typing rates over
      10 correct characters per minute. The participant used this interface to
      communicate face-to-face with research staff by using text-to-speech conversion,
      and remotely using an internet chat application. This study demonstrates the
      first use of an intracortical brain-computer interface for neural point-and-click
      communication by an individual with incomplete locked-in syndrome. 

PMID- 25385767
TI  - Plant-insect interactions under bacterial influence: ecological implications and
      underlying mechanisms.
AB  - Plants and insects have been co-existing for more than 400 million years, leading
      to intimate and complex relationships. Throughout their own evolutionary history,
      plants and insects have also established intricate and very diverse relationships
      with microbial associates. Studies in recent years have revealed plant- or insect
      associated microbes to be instrumental in plant-insect interactions, with
      important implications for plant defences and plant utilization by insects.
      Microbial communities associated with plants are rich in diversity, and their
      structure greatly differs between below- and above-ground levels. Microbial
      communities associated with insect herbivores generally present a lower diversity
      and can reside in different body parts of their hosts including bacteriocytes,
      haemolymph, gut, and salivary glands. Acquisition of microbial communities by
      vertical or horizontal transmission and possible genetic exchanges through
      lateral transfer could strongly impact on the host insect or plant fitness by
      conferring adaptations to new habitats. Recent developments in sequencing
      technologies and molecular tools have dramatically enhanced opportunities to
      characterize the microbial diversity associated with plants and insects and have
      unveiled some of the mechanisms by which symbionts modulate plant-insect
      interactions. Here, we focus on the diversity and ecological consequences of
      bacterial communities associated with plants and herbivorous insects. We also
      highlight the known mechanisms by which these microbes interfere with plant
      insect interactions. Revealing such mechanisms in model systems under controlled
      environments but also in more natural ecological settings will help us to
      understand the evolution of complex multitrophic interactions in which plants,
      herbivorous insects, and micro-organisms are inserted. 

PMID- 25385766
TI  - Plasma membrane receptor-like kinase leaf panicle 2 acts downstream of the
      DROUGHT AND SALT TOLERANCE transcription factor to regulate drought sensitivity
      in rice.
AB  - Drought is a recurring climatic hazard that reduces the crop yields. To avoid the
      negative effects of drought on crop production, extensive efforts have been
      devoted to investigating the complex mechanisms of gene expression and signal
      transduction during drought stress. Receptor-like kinases (RLKs) play important
      roles in perceiving extracellular stimuli and activating downstream signalling
      responses. The rice genome contains >1100 RLK genes, of which only two are
      reported to function in drought stress. A leucine-rich repeat (LRR)-RLK gene
      named Leaf Panicle 2 (LP2) was previously found to be strongly expressed in
      leaves and other photosynthetic tissues, but its function remains unclear. In the
      present study, it was shown that the expression of LP2 was down-regulated by
      drought and abscisic acid (ABA). Transgenic plants overexpressing LP2 accumulated
      less H2O2, had more open stomata in leaves, and showed hypersensitivity to
      drought stress. Further investigation revealed that transcription of LP2 was
      directly regulated by the zinc finger transcription factor DROUGHT AND SALT
      TOLERANCE (DST). In addition, LP2 was identified as a functional kinase localized
      to the plasma membrane and interacted with the drought-responsive aquaporin
      proteins OsPIP1; 1, OsPIP1; 3, and OsPIP2; 3. Thus, the findings provided
      evidence that the LRR-RLK LP2, transcriptionally regulated by the drought-related
      transcription factor DST, served as a negative regulator in drought response.

PMID- 25385768
TI  - Drought stress tolerance in grapevine involves activation of polyamine oxidation
      contributing to improved immune response and low susceptibility to Botrytis
      cinerea.
AB  - Environmental factors including drought stress may modulate plant immune
      responses and resistance to pathogens. However, the relationship between
      mechanisms of drought tolerance and resistance to pathogens remained unknown. In
      this study, the effects of drought stress on polyamine (PA) homeostasis and
      immune responses were investigated in two grapevine genotypes differing in their
      drought tolerance; Chardonnay (CHR), as sensitive and Meski (MSK), as tolerant.
      Under drought conditions, MSK plants showed the lowest leaf water loss and
      reduction of photosynthetic efficiency, and expressed a lower level of NCED2, a
      gene involved in abscisic acid biosynthesis, compared with CHR plants. The
      improved drought tolerance in MSK was also coincident with the highest change in
      free PAs and up-regulation of the genes encoding arginine decarboxylase (ADC),
      copper amine-oxidase (CuAO), and PA-oxidases (PAO) and their corresponding enzyme
      activities. MSK plants also accumulated the highest level of amino acids,
      including Arg, Glu, Gln, Pro, and GABA, emphasizing the participation of PA
      related amino acid homeostasis in drought tolerance. Importantly, drought
      tolerant plants also exhibited enhanced phytoalexin accumulation and up
      regulation of PR genes, especially PR-2 and Chit4c, compared with the sensitive
      plants. This is consistent with a lower susceptibility of MSK than CHR to
      Botrytis cinerea. Data suggest a possible connection between water stress
      tolerance and immune response in grapevine. Pharmacological experiments revealed
      that under drought conditions CuAO and PAO pathways were involved in the
      regulation of photosynthetic efficiency, and also of immune response and
      resistance of grapevine to a subsequent pathogen attack. These results open new
      views to improve our understanding of crosstalk between drought tolerance
      mechanisms and immune response. 

PMID- 25385769
TI  - Different roles for RNA silencing and RNA processing components in virus recovery
      and virus-induced gene silencing in plants.
AB  - A major antiviral mechanism in plants is mediated by RNA silencing, which relies
      on the cleavage of viral dsRNA into virus-derived small interfering RNAs
      (vsiRNAs) by DICER-like enzymes. Members of the Argonaute (AGO) family of
      endonucleases then use these vsiRNA as guides to target viral RNA. This can
      result in a phenomenon known as recovery, whereby the plant silences viral gene
      expression and recovers from viral symptoms. Endogenous mRNAs can also be
      targeted by vsiRNAs in a phenomenon known as virus-induced gene silencing (VIGS).
      Although related to other RNA silencing mechanisms, it has not been established
      if recovery and VIGS are mediated by the same molecular mechanisms. We used
      tobacco rattle virus (TRV) carrying a fragment of the phytoene desaturase (PDS)
      gene (TRV-PDS) or expressing green fluorescent protein (TRV-GFP) as readouts for
      VIGS and recovery, respectively, in Arabidopsis ago mutants. Our results
      demonstrated roles for AGO2 and AGO4 in susceptibility to TRV, whereas VIGS of
      endogenous genes appeared to be largely mediated by AGO1. However, recovery
      appeared to be mediated by different components, as all the aforementioned
      mutants were able to recover from TRV-GFP inoculation. TRV RNAs from recovered
      plants associated less with ribosomes, suggesting that recovery involves
      translational repression of viral transcripts. Translationally repressed RNAs
      often accumulate in RNA processing bodies (PBs), where they are eventually
      processed by decapping enzymes. Consistent with this, we found that viral
      recovery induced increased PB formation and that a decapping mutant (DCP2) showed
      increased VIGS and virus RNA accumulation, indicating an important role for PBs
      in eliminating viral RNA. 

PMID- 25385770
TI  - Communicative rhythms in brain and behaviour.

PMID- 25385771
TI  - Exploring how musical rhythm entrains brain activity with electroencephalogram
      frequency-tagging.
AB  - The ability to perceive a regular beat in music and synchronize to this beat is a
      widespread human skill. Fundamental to musical behaviour, beat and meter refer to
      the perception of periodicities while listening to musical rhythms and often
      involve spontaneous entrainment to move on these periodicities. Here, we present
      a novel experimental approach inspired by the frequency-tagging approach to
      understand the perception and production of rhythmic inputs. This approach is
      illustrated here by recording the human electroencephalogram responses at beat
      and meter frequencies elicited in various contexts: mental imagery of meter,
      spontaneous induction of a beat from rhythmic patterns, multisensory integration
      and sensorimotor synchronization. Collectively, our observations support the view
      that entrainment and resonance phenomena subtend the processing of musical
      rhythms in the human brain. More generally, they highlight the potential of this
      approach to help us understand the link between the phenomenology of musical beat
      and meter and the bias towards periodicities arising under certain circumstances
      in the nervous system. Entrainment to music provides a highly valuable framework
      to explore general entrainment mechanisms as embodied in the human brain. 

PMID- 25385773
TI  - Timing in talking: what is it used for, and how is it controlled?
AB  - In the first part of the paper, we summarize the linguistic factors that shape
      speech timing patterns, including the prosodic structures which govern them, and
      suggest that speech timing patterns are used to aid utterance recognition. In the
      spirit of optimal control theory, we propose that recognition requirements are
      balanced against requirements such as rate of speech and style, as well as
      movement costs, to yield (near-)optimal planned surface timing patterns;
      additional factors may influence the implementation of that plan. In the second
      part of the paper, we discuss theories of timing control in models of speech
      production and motor control. We present three types of evidence that support
      models of speech production that involve extrinsic timing. These include (i)
      increasing variability with increases in interval duration, (ii) evidence that
      speakers refer to and plan surface durations, and (iii) independent timing of
      movement onsets and offsets. 

PMID- 25385772
TI  - Rhythm in joint action: psychological and neurophysiological mechanisms for real
      time interpersonal coordination.
AB  - Human interaction often requires simultaneous precision and flexibility in the
      coordination of rhythmic behaviour between individuals engaged in joint activity,
      for example, playing a musical duet or dancing with a partner. This review
      article addresses the psychological processes and brain mechanisms that enable
      such rhythmic interpersonal coordination. First, an overview is given of research
      on the cognitive-motor processes that enable individuals to represent joint
      action goals and to anticipate, attend and adapt to other's actions in real time.
      Second, the neurophysiological mechanisms that underpin rhythmic interpersonal
      coordination are sought in studies of sensorimotor and cognitive processes that
      play a role in the representation and integration of self- and other-related
      actions within and between individuals' brains. Finally, relationships between
      social-psychological factors and rhythmic interpersonal coordination are
      considered from two perspectives, one concerning how social-cognitive tendencies
      (e.g. empathy) affect coordination, and the other concerning how coordination
      affects interpersonal affiliation, trust and prosocial behaviour. Our review
      highlights musical ensemble performance as an ecologically valid yet readily
      controlled domain for investigating rhythm in joint action. 

PMID- 25385774
TI  - Speech rhythm: a metaphor?
AB  - Is speech rhythmic? In the absence of evidence for a traditional view that
      languages strive to coordinate either syllables or stress-feet with regular time
      intervals, we consider the alternative that languages exhibit contrastive rhythm
      subsisting merely in the alternation of stronger and weaker elements. This is
      initially plausible, particularly for languages with a steep 'prominence
      gradient', i.e. a large disparity between stronger and weaker elements; but we
      point out that alternation is poorly achieved even by a 'stress-timed' language
      such as English, and, historically, languages have conspicuously failed to adopt
      simple phonological remedies that would ensure alternation. Languages seem more
      concerned to allow 'syntagmatic contrast' between successive units and to use
      durational effects to support linguistic functions than to facilitate rhythm.
      Furthermore, some languages (e.g. Tamil, Korean) lack the lexical prominence
      which would most straightforwardly underpin prominence of alternation. We
      conclude that speech is not incontestibly rhythmic, and may even be antirhythmic.
      However, its linguistic structure and patterning allow the metaphorical extension
      of rhythm in varying degrees and in different ways depending on the language, and
      it is this analogical process which allows speech to be matched to external
      rhythms. 

PMID- 25385775
TI  - Gestural coordination at prosodic boundaries and its role for prosodic structure
      and speech planning processes.
AB  - Prosodic structure is a grammatical component that serves multiple functions in
      the production, comprehension and acquisition of language. Prosodic boundaries
      are critical for the understanding of the nature of the prosodic structure of
      language, and important progress has been made in the past decades in
      illuminating their properties. We first review recent prosodic boundary research
      from the point of view of gestural coordination. We then go on to tie in this
      work to questions of speech planning and manual and head movement. We conclude
      with an outline of a new direction of research which is needed for a full
      understanding of prosodic boundaries and their role in the speech production
      process. 

PMID- 25385776
TI  - Situational influences on rhythmicity in speech, music, and their interaction.
AB  - Brain processes underlying the production and perception of rhythm indicate
      considerable flexibility in how physical signals are interpreted. This paper
      explores how that flexibility might play out in rhythmicity in speech and music.
      There is much in common across the two domains, but there are also significant
      differences. Interpretations are explored that reconcile some of the differences,
      particularly with respect to how functional properties modify the rhythmicity of
      speech, within limits imposed by its structural constraints. Functional and
      structural differences mean that music is typically more rhythmic than speech,
      and that speech will be more rhythmic when the emotions are more strongly
      engaged, or intended to be engaged. The influence of rhythmicity on attention is
      acknowledged, and it is suggested that local increases in rhythmicity occur at
      times when attention is required to coordinate joint action, whether in talking
      or music-making. Evidence is presented which suggests that while these short
      phases of heightened rhythmical behaviour are crucial to the success of
      transitions in communicative interaction, their modality is immaterial: they all
      function to enhance precise temporal prediction and hence tightly coordinated
      joint action. 

PMID- 25385777
TI  - Take a breath and take the turn: how breathing meets turns in spontaneous
      dialogue.
AB  - Physiological rhythms are sensitive to social interactions and could contribute
      to defining social rhythms. Nevertheless, our knowledge of the implications of
      breathing in conversational turn exchanges remains limited. In this paper, we
      addressed the idea that breathing may contribute to timing and coordination
      between dialogue partners. The relationships between turns and breathing were
      analysed in unconstrained face-to-face conversations involving female speakers.
      No overall relationship between breathing and turn-taking rates was observed, as
      breathing rate was specific to the subjects' activity in dialogue (listening
      versus taking the turn versus holding the turn). A general inter-personal
      coordination of breathing over the whole conversation was not evident. However,
      specific coordinative patterns were observed in shorter time-windows when
      participants engaged in taking turns. The type of turn-taking had an effect on
      the respective coordination in breathing. Most of the smooth and interrupted
      turns were taken just after an inhalation, with specific profiles of alignment to
      partner breathing. Unsuccessful attempts to take the turn were initiated late in
      the exhalation phase and with no clear inter-personal coordination. Finally,
      breathing profiles at turn-taking were different than those at turn-holding. The
      results support the idea that breathing is actively involved in turn-taking and
      turn-holding. 

PMID- 25385778
TI  - Fourteen-month-old infants use interpersonal synchrony as a cue to direct
      helpfulness.
AB  - Musical behaviours such as dancing, singing and music production, which require
      the ability to entrain to a rhythmic beat, encourage high levels of interpersonal
      coordination. Such coordination has been associated with increased group cohesion
      and social bonding between group members. Previously, we demonstrated that this
      association influences even the social behaviour of 14-month-old infants. Infants
      were significantly more likely to display helpfulness towards an adult
      experimenter following synchronous bouncing compared with asynchronous bouncing
      to music. The present experiment was designed to determine whether interpersonal
      synchrony acts as a cue for 14-month-olds to direct their prosocial behaviours to
      specific individuals with whom they have experienced synchronous movement, or
      whether it acts as a social prime, increasing prosocial behaviour in general.
      Consistent with the previous results, infants were significantly more likely to
      help an experimenter following synchronous versus asynchronous movement with this
      person. Furthermore, this manipulation did not affect infant's behaviour towards
      a neutral stranger, who was not involved in any movement experience. This
      indicates that synchronous bouncing acts as a social cue for directing
      prosociality. These results have implications for how musical engagement and
      rhythmic synchrony affect social behaviour very early in development. 

PMID- 25385779
TI  - Attentional entrainment and perceived event duration.
AB  - This study considered the contribution of dynamic attending theory (DAT) and
      attentional entrainment to systematic distortions in perceived event duration.
      Three experiments were conducted using an auditory oddball paradigm, in which
      listeners judged the duration of a deviant (oddball) stimulus embedded within a
      series of identical (standard) stimuli. To test for a role of attentional
      entrainment in perceived oddball duration, oddballs were presented at either
      temporally expected (on time) or unexpectedly early or late time points relative
      to extrapolation of the context rhythm. Consistent with involvement of
      attentional entrainment in perceived duration, duration judgements about the
      oddball were least distorted when the oddball occurred on time with respect to
      the entrained rhythm, whereas durations of early and late oddballs were perceived
      to be shorter and longer, respectively. This pattern of results was independent
      of the absolute time interval preceding the oddball. Moreover, as expected, an
      irregularly timed sequence context weakened observed differences between oddballs
      with on-time and late onsets. Combined with other recent work on the role of
      temporal preparation in duration distortions, the present findings allot at least
      a portion of the oddball effect to increased attention to events that are more
      expected, rather than on their unexpected nature per se. 

PMID- 25385780
TI  - Auditory rhythmic cueing in movement rehabilitation: findings and possible
      mechanisms.
AB  - Moving to music is intuitive and spontaneous, and music is widely used to support
      movement, most commonly during exercise. Auditory cues are increasingly also used
      in the rehabilitation of disordered movement, by aligning actions to sounds such
      as a metronome or music. Here, the effect of rhythmic auditory cueing on movement
      is discussed and representative findings of cued movement rehabilitation are
      considered for several movement disorders, specifically post-stroke motor
      impairment, Parkinson's disease and Huntington's disease. There are multiple
      explanations for the efficacy of cued movement practice. Potentially relevant,
      non-mutually exclusive mechanisms include the acceleration of learning;
      qualitatively different motor learning owing to an auditory context; effects of
      increased temporal skills through rhythmic practices and motivational aspects of
      musical rhythm. Further considerations of rehabilitation paradigm efficacy focus
      on specific movement disorders, intervention methods and complexity of the
      auditory cues. Although clinical interventions using rhythmic auditory cueing do
      not show consistently positive results, it is argued that internal mechanisms of
      temporal prediction and tracking are crucial, and further research may inform
      rehabilitation practice to increase intervention efficacy. 

PMID- 25385781
TI  - Cerebellum, temporal predictability and the updating of a mental model.
AB  - We live in a dynamic and changing environment, which necessitates that we adapt
      to and efficiently respond to changes of stimulus form ('what') and stimulus
      occurrence ('when'). Consequently, behaviour is optimal when we can anticipate
      both the 'what' and 'when' dimensions of a stimulus. For example, to perceive a
      temporally expected stimulus, a listener needs to establish a fairly precise
      internal representation of its external temporal structure, a function ascribed
      to classical sensorimotor areas such as the cerebellum. Here we investigated how
      patients with cerebellar lesions and healthy matched controls exploit temporal
      regularity during auditory deviance processing. We expected modulations of the
      N2b and P3b components of the event-related potential in response to deviant
      tones, and also a stronger P3b response when deviant tones are embedded in
      temporally regular compared to irregular tone sequences. We further tested to
      what degree structural damage to the cerebellar temporal processing system
      affects the N2b and P3b responses associated with voluntary attention to change
      detection and the predictive adaptation of a mental model of the environment,
      respectively. Results revealed that healthy controls and cerebellar patients
      display an increased N2b response to deviant tones independent of temporal
      context. However, while healthy controls showed the expected enhanced P3b
      response to deviant tones in temporally regular sequences, the P3b response in
      cerebellar patients was significantly smaller in these sequences. The current
      data provide evidence that structural damage to the cerebellum affects the
      predictive adaptation to the temporal structure of events and the updating of a
      mental model of the environment under voluntary attention. 

PMID- 25385782
TI  - Quantification of rhythm problems in disordered speech: a re-evaluation.
AB  - Disordered speech can present with rhythmic problems, impacting on an
      individual's ability to communicate. Effective treatment relies on the
      availability of sensitive methods to characterize the problem. Rhythm metrics
      based on segmental durations originally designed for cross-linguistic research
      have the potential to provide such information. However, these measures may be
      associated with problems that impact on their clinical usefulness. This paper
      aims to address the perceptual validity of cross-linguistic metrics as indicators
      of rhythmic disorder. Speakers with dysarthria and matched healthy participants
      performed a range of tasks, including syllable and sentence repetition and a
      spontaneous monologue. A range of rhythm metrics as well as clinical measures
      were applied. Results showed that none of the metrics could differentiate
      disordered from healthy speakers, despite clear perceptual differences,
      suggesting that factors beyond segment duration impacted on rhythm perception.
      The investigation also highlighted a number of areas where caution needs to be
      exercised in the application of rhythm metrics to disordered speech. The paper
      concludes that the underlying speech impairment leading to the perceptual and
      acoustic characterization of rhythmic problems needs to be established through
      detailed analysis of speech characteristics in order to construct effective
      treatment plans for individuals with speech disorders. 

PMID- 25385783
TI  - Losing the beat: deficits in temporal coordination.
AB  - Tapping or clapping to an auditory beat, an easy task for most individuals,
      reveals precise temporal synchronization with auditory patterns such as music,
      even in the presence of temporal fluctuations. Most models of beat-tracking rely
      on the theoretical concept of pulse: a perceived regular beat generated by an
      internal oscillation that forms the foundation of entrainment abilities. Although
      tapping to the beat is a natural sensorimotor activity for most individuals, not
      everyone can track an auditory beat. Recently, the case of Mathieu was documented
      (Phillips-Silver et al. 2011 Neuropsychologia 49, 961-969.
      (doi:10.1016/j.neuropsychologia.2011.02.002)). Mathieu presented himself as
      having difficulty following a beat and exhibited synchronization failures. We
      examined beat-tracking in normal control participants, Mathieu, and a second beat
      deaf individual, who tapped with an auditory metronome in which unpredictable
      perturbations were introduced to disrupt entrainment. Both beat-deaf cases
      exhibited failures in error correction in response to the perturbation task while
      exhibiting normal spontaneous motor tempi (in the absence of an auditory
      stimulus), supporting a deficit specific to perception-action coupling. A damped
      harmonic oscillator model was applied to the temporal adaptation responses; the
      model's parameters of relaxation time and endogenous frequency accounted for
      differences between the beat-deaf cases as well as the control group individuals.

PMID- 25385785
TI  - An old probe sheds new light on BK channel pore structure.

PMID- 25385786
TI  - Volatile anesthetics inhibit sodium channels without altering bulk lipid bilayer
      properties.
AB  - Although general anesthetics are clinically important and widely used, their
      molecular mechanisms of action remain poorly understood. Volatile anesthetics
      such as isoflurane (ISO) are thought to alter neuronal function by depressing
      excitatory and facilitating inhibitory neurotransmission through direct
      interactions with specific protein targets, including voltage-gated sodium
      channels (Na(v)). Many anesthetics alter lipid bilayer properties, suggesting
      that ion channel function might also be altered indirectly through effects on the
      lipid bilayer. We compared the effects of ISO and of a series of fluorobenzene
      (FB) model volatile anesthetics on Na(v) function and lipid bilayer properties.
      We examined the effects of these agents on Na(v) in neuronal cells using whole
      cell electrophysiology, and on lipid bilayer properties using a gramicidin-based
      fluorescence assay, which is a functional assay for detecting changes in lipid
      bilayer properties sensed by a bilayer-spanning ion channel. At clinically
      relevant concentrations (defined by the minimum alveolar concentration), both the
      FBs and ISO produced prepulse-dependent inhibition of Na(v) and shifted the
      voltage dependence of inactivation toward more hyperpolarized potentials without
      affecting lipid bilayer properties, as sensed by gramicidin channels. Only at
      supra-anesthetic (toxic) concentrations did ISO alter lipid bilayer properties.
      These results suggest that clinically relevant concentrations of volatile
      anesthetics alter Na(v) function through direct interactions with the channel
      protein with little, if any, contribution from changes in bulk lipid bilayer
      properties. Our findings further suggest that changes in lipid bilayer properties
      are not involved in clinical anesthesia.

PMID- 25385787
TI  - Capturing distinct KCNQ2 channel resting states by metal ion bridges in the
      voltage-sensor domain.
AB  - Although crystal structures of various voltage-gated K(+) (Kv) and Na(+) channels
      have provided substantial information on the activated conformation of the
      voltage-sensing domain (VSD), the topology of the VSD in its resting conformation
      remains highly debated. Numerous studies have investigated the VSD resting state
      in the Kv Shaker channel; however, few studies have explored this issue in other
      Kv channels. Here, we investigated the VSD resting state of KCNQ2, a K(+) channel
      subunit belonging to the KCNQ (Kv7) subfamily of Kv channels. KCNQ2 can
      coassemble with the KCNQ3 subunit to mediate the IM current that regulates
      neuronal excitability. In humans, mutations in KCNQ2 are associated with benign
      neonatal forms of epilepsy or with severe epileptic encephalopathy. We introduced
      cysteine mutations into the S4 transmembrane segment of the KCNQ2 VSD and
      determined that external application of Cd(2+) profoundly reduced the current
      amplitude of S4 cysteine mutants S195C, R198C, and R201C. Based on reactivity
      with the externally accessible endogenous cysteine C106 in S1, we infer that each
      of the above S4 cysteine mutants forms Cd(2+) bridges to stabilize a channel
      closed state. Disulfide bonds and metal bridges constrain the S4 residues S195,
      R198, and R201 near C106 in S1 in the resting state, and experiments using
      concatenated tetrameric constructs indicate that this occurs within the same VSD.
      KCNQ2 structural models suggest that three distinct resting channel states have
      been captured by the formation of different S4-S1 Cd(2+) bridges. Collectively,
      this work reveals that residue C106 in S1 can be very close to several N-terminal
      S4 residues for stabilizing different KCNQ2 resting conformations. 

PMID- 25385788
TI  - Imaging neuroinflammation in gray and white matter in schizophrenia: an in-vivo
      PET study with [18F]-FEPPA.
AB  - Neuroinflammation and abnormal immune responses have been implicated in
      schizophrenia (SCZ). Past studies using positron emission tomography (PET) that
      examined neuroinflammation in patients with SCZ in vivo using the translocator
      protein 18kDa (TSPO) target were limited by the insensitivity of the first
      generation imaging agent [(11)C]-PK11195, scanners used, and the small sample
      sizes studied. Present study uses a novel second-generation TSPO PET radioligand
      N-acetyl-N-(2-[(18)F]fluoroethoxybenzyl)-2-phenoxy-5-pyridinamine ([(18)F]-FEPPA)
      to evaluate whether there is increased neuroinflammation in patients with SCZ. A
      cross-sectional study was performed using [(18)F]-FEPPA and a high-resolution
      research tomograph (HRRT). Eighteen patients with SCZ with ongoing psychotic
      symptoms and 27 healthy volunteers (HV) were recruited from a tertiary
      psychiatric clinical setting and the community, respectively. All participants
      underwent [(18)F]-FEPPA PET and magnetic resonance imaging, and PET data were
      analyzed to obtain [(18)F]-FEPPA total volume of distribution (VT) using a 2
      tissue compartment model with an arterial plasma input function, as previously
      validated. All subjects were classified as high-, medium- or low-affinity [(18)F]
      FEPPA binders on the basis of rs6971 polymorphism, and genotype information was
      incorporated into the analyses of imaging outcomes. No significant differences in
      neuroinflammation indexed as [(18)F]-FEPPA VT were observed between groups in
      either gray (F(1,39) = 0.179, P = .674) or white matter regions (F(1,38) = 0.597,
      P = .445). The lack of significant difference in neuroinflammation in treated
      patients with SCZ in the midst of a psychotic episode and HV suggests that
      neuroinflammatory processes may take place early in disease progression or are
      affected by antipsychotic treatment.

PMID- 25385789
TI  - Meta-Analysis of Anti-Toxoplasma gondii IgM Antibodies in Acute Psychosis.
AB  - INTRODUCTION: A number of different infections are associated with acute
      psychosis. However, relationships between infections and acute psychosis in
      patients with schizophrenia have not been extensively explored. Exposure to
      Toxoplasma gondii is a replicated risk factor for schizophrenia. Previous studies
      have focused on T. gondii IgG antibodies, which are a marker of lifetime
      exposure, whereas IgM antibodies are a marker of acute/recent exposure,
      persistent infection, or reinfection. We performed a meta-analysis of T. gondii
      IgM antibodies and acute psychosis, to further investigate whether infections may
      be associated with relapse in schizophrenia. METHODS: We identified articles by
      systematic searches of PubMed, PsycINFO, and ISI databases. We included studies,
      in English, of serum T. gondii IgM antibodies in patients with acute psychosis
      and controls. RESULTS: Sixteen independent samples (2353 patients and 1707
      controls) met inclusion criteria. Data were pooled using a random effects model.
      There was a significant increase in risk of positive T. gondii IgM antibodies in
      acute psychosis compared with controls (7.6% vs 5.7%, OR = 1.68, 95% CI = 1.23
      2.27, P = .001). The association was stronger for patients with chronic
      schizophrenia (8.7% vs 4.6%, OR = 2.54, 95% CI = 1.63-3.96, P < .001) than first
      episode psychosis. In meta-regression analyses, age, sex, and publication year
      were unrelated to the association; however, there was a significant association
      with geographic region. DISCUSSION: An increased seroprevalence of T. gondii IgM
      in patients with acute psychosis complements and extends previous findings,
      suggesting that infections may be relevant to the etiopathophysiology of relapse
      in some patients with schizophrenia.

PMID- 25385790
TI  - The two-component system GrvRS (EtaRS) regulates ace expression in Enterococcus
      faecalis OG1RF.
AB  - Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a
      virulence factor in endocarditis and urinary tract infection models, has been
      shown to increase under certain conditions, such as in the presence of serum,
      bile salts, urine, and collagen and at 46  degrees C. However, the mechanism of
      ace/Ace regulation under different conditions is still unknown. In this study, we
      identified a two-component regulatory system GrvRS as the main regulator of ace
      expression under these stress conditions. Using Northern hybridization and beta
      galactosidase assays of an ace promoter-lacZ fusion, we found transcription of
      ace to be virtually absent in a grvR deletion mutant under the conditions that
      increase ace expression in wild-type OG1RF and in the complemented strain.
      Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation
      as well as attenuation in a murine urinary tract infection model. Here we show
      that GrvR plays a major role in control of ace expression and E. faecalis
      virulence.

PMID- 25385791
TI  - Late establishment of the attaching and effacing lesion caused by atypical
      enteropathogenic Escherichia coli depends on protein expression regulated by Per.
AB  - Enteropathogenic Escherichia coli (EPEC) is classified as typical (tEPEC) or
      atypical (aEPEC) based on the presence or absence of the E. coli adherence factor
      plasmid (pEAF), respectively. The hallmark of EPEC infection is the formation of
      the attaching and effacing (A/E) lesions on the gut mucosa. We compared the
      kinetics of A/E lesion formation induced by aEPEC and tEPEC. The examination of
      infected HEp-2 cells clearly demonstrated delayed A/E lesion formation by aEPEC
      in comparison to tEPEC. This delay was associated with the expression of locus of
      enterocyte effacement (LEE)-encoded virulence factors (i.e., intimin and EspD).
      Indeed, the insertion of a plasmid containing perABC, a transcriptional regulator
      of virulence factors involved in A/E formation, into aEPEC strains increased and
      accelerated the formation of A/E lesions. Interestingly, the enhanced expression
      and translocation of LEE-encoded proteins, such as those expressed in LEE5
      (intimin) and LEE4 (EspD), in aEPEC (perABC) was independent of bacterial
      adhesion. The secretion kinetics of these two proteins representing LEE5 and LEE4
      expression correlated with A/E lesion formation. We conclude that the lack of Per
      in the regulation network of virulence genes is one of the main factors that
      delay the establishment of A/E lesions induced by aEPEC strains. 

PMID- 25385792
TI  - Gastrointestinal dissemination and transmission of Staphylococcus aureus
      following bacteremia.
AB  - Mutations that alter virulence and antibiotic susceptibility arise and persist
      during Staphylococcus aureus bacteremia. However, an experimental system
      demonstrating transmission following bacteremia has been lacking, and thus
      implications of within-host adaptation for between-host transmission are unknown.
      We report that S. aureus disseminates to the gastrointestinal tract of mice
      following intravenous injection and readily transmits to cohoused naive mice.
      Both intestinal dissemination and transmission were linked to the production of
      virulence factors based on gene deletion studies of the sae and agr two-component
      systems. Furthermore, antimicrobial selection for antibiotic-resistant S. aureus
      displaced susceptible S. aureus from the intestine of infected hosts, which led
      to the preferential transmission and dominance of antibiotic-resistant bacteria
      among cohoused untreated mice. These findings establish an animal model to
      investigate gastrointestinal dissemination and transmission of S. aureus and
      suggest that adaptation during the course of systemic infection has implications
      beyond the level of a single host. 

PMID- 25385793
TI  - The polyamine N-acetyltransferase-like enzyme PmvE plays a role in the virulence
      of Enterococcus faecalis.
AB  - We previously showed that the mutant strain of Enterococcus faecalis lacking the
      transcriptional regulator SlyA is more virulent than the parental strain. We
      hypothesized that this phenotype was due to overexpression of the second gene of
      the slyA operon, ef_3001, renamed pmvE (for polyamine metabolism and virulence of
      E. faecalis). PmvE shares strong homologies with N(1)-spermidine/spermine
      acetyltransferase enzymes involved in the metabolism of polyamines. In this
      study, we used an E. faecalis strain carrying the recombinant plasmid pMSP3535
      pmvE (V19/p3535-pmvE), which allows the induction of pmvE by addition of nisin.
      Thereby, we showed that the overexpression of PmvE increased the virulence of E.
      faecalis in the Galleria mellonella infection model, as well as the persistence
      within peritoneal macrophages. We were also able to show a direct interaction
      between the His-tagged recombinant PmvE (rPmvE) protein and putrescine by the
      surface plasmon resonance (SPR) technique on a Biacore instrument. Moreover,
      biochemical assays showed that PmvE possesses an N-acetyltransferase activity
      toward polyamine substrates. Our results suggest that PmvE contributes to the
      virulence of E. faecalis, likely through its involvement in the polyamine
      metabolism. 

PMID- 25385794
TI  - Enterococcus faecalis 6-phosphogluconolactonase is required for both commensal
      and pathogenic interactions with Manduca sexta.
AB  - Enterococcus faecalis is a commensal and pathogen of humans and insects. In
      Manduca sexta, E. faecalis is an infrequent member of the commensal gut
      community, but its translocation to the hemocoel results in a commensal-to
      pathogen switch. To investigate E. faecalis factors required for commensalism, we
      identified E. faecalis genes that are upregulated in the gut of M. sexta using
      recombinase-based in vivo expression technology (RIVET). The RIVET screen
      produced 113 clones, from which we identified 50 genes that are more highly
      expressed in the insect gut than in culture. The most frequently recovered gene
      was locus OG1RF_11582, which encodes a 6-phosphogluconolactonase that we
      designated pglA. A pglA deletion mutant was impaired in both pathogenesis and gut
      persistence in M. sexta and produced enhanced biofilms compared with the wild
      type in an in vitro polystyrene plate assay. Mutation of four other genes
      identified by RIVET did not affect persistence in caterpillar guts but led to
      impaired pathogenesis. This is the first identification of genetic determinants
      for E. faecalis commensal and pathogenic interactions with M. sexta. Bacterial
      factors identified in this model system may provide insight into colonization or
      persistence in other host-associated microbial communities and represent
      potential targets for interventions to prevent E. faecalis infections. 

PMID- 25385795
TI  - Prolonged growth of a clinical Staphylococcus aureus strain selects for a stable
      small-colony-variant cell type.
AB  - An undetermined feature of Staphylococcus aureus pathogenesis is its persistence
      and then relapse of disease. This has been explained by its switch to alternative
      lifestyles, mainly as biofilm or small-colony variants (SCVs). Studying the
      native characteristics of SCVs has been problematic due to their reversion to the
      parental lifestyle. We have observed that for a number of S. aureus strains as
      they switch to an SCV lifestyle, there is the formation of an extracellular
      matrix. We focused our analysis on one strain, WCH-SK2. For bacterial survival in
      the host, the combination of low nutrients and the prolonged time frame forms a
      stress that selects for a specific cell type from the population. In this
      context, we used steady-state growth conditions with low nutrients and a
      controlled low growth rate for a prolonged time and with methylglyoxal. These
      conditions induced S. aureus WCH-SK2 into a stable SCV cell type; the cells did
      not revert after subculturing. Analysis revealed these cells possessed a
      metabolic and surface profile that was different from those of previously
      described SCVs or biofilm cells. The extracellular matrix was protein and
      extracellular DNA but not polysaccharide. The SCV cells induced expression of
      certain surface proteins (such as Ebh) and synthesis of lantibiotics while
      downregulating factors that stimulate the immune response (leucocidin, capsule,
      and carotenoid). Our data reveal cell heterogeneity within an S. aureus
      population and under conditions that resemble long-term survival in the host have
      identified a previously unnoticed S. aureus cell type with a distinctive
      metabolic and molecular profile. 

PMID- 25385796
TI  - What is a host? Incorporating the microbiota into the damage-response framework.
AB  - Since proof of the germ theory of disease in the late 19th century, a major focus
      of the fields of microbiology and infectious diseases has been to seek
      differences between pathogenic and nonpathogenic microbes and the role that the
      host plays in microbial pathogenesis. Remarkably, despite the increasing
      recognition that host immunity plays a role in microbial pathogenesis, there has
      been little discussion about what constitutes a host. Historically, hosts have
      been viewed in the context of their fitness or immunological status and
      characterized by adjectives such as immune, immunocompetent, immunosuppressed,
      immunocompromised, or immunologically impaired. However, in recent years it has
      become apparent that the microbiota has profound effects on host homeostasis and
      susceptibility to microbial diseases in addition to its effects on host immunity.
      This raises the question of how to incorporate the microbiota into defining a
      host. This definitional problem is further complicated because neither host nor
      microbial properties are adequate to predict the outcome of host-microbe
      interaction because this outcome exhibits emergent properties. In this essay, we
      revisit the damage-response framework (DRF) of microbial pathogenesis and
      demonstrate how it can incorporate the rapidly accumulating information being
      generated by the microbiome revolution. We use the tenets of the DRF to put forth
      the following definition of a host: a host is an entity that houses an associated
      microbiome/microbiota and interacts with microbes such that the outcome results
      in damage, benefit, or indifference, thus resulting in the states of symbiosis,
      colonization, commensalism, latency, and disease. 

PMID- 25385797
TI  - Toxin-mediated paracellular transport of antitoxin antibodies facilitates
      protection against Clostridium difficile infection.
AB  - The exotoxins TcdA and TcdB are the major virulence factors of Clostridium
      difficile. Circulating neutralizing antitoxin antibodies are protective in C.
      difficile infection (CDI), as demonstrated, in part, by the protective effects of
      actoxumab and bezlotoxumab, which bind to and neutralize TcdA and TcdB,
      respectively. The question of how systemic IgG antibodies neutralize toxins in
      the gut lumen remains unresolved, although it has been suggested that the Fc
      receptor FcRn may be involved in active antibody transport across the gut
      epithelium. In this study, we demonstrated that genetic ablation of FcRn and
      excess irrelevant human IgG have no impact on actoxumab-bezlotoxumab-mediated
      protection in murine and hamster models of CDI, suggesting that Fc-dependent
      transport of antibodies across the gut wall is not required for efficacy. Tissue
      distribution studies in hamsters suggest, rather, that the transport of
      antibodies depends on toxin-induced damage to the gut lining. In an in vitro two
      dimensional culture system that mimics the architecture of the intestinal mucosal
      epithelium, toxins on the apical side of epithelial cell monolayers are
      neutralized by basolateral antibodies, and antibody transport across the cell
      layer is dramatically increased upon addition of toxin to the apical side.
      Similar data were obtained with F(ab')2 fragments, which lack an Fc domain,
      consistent with FcRn-independent paracellular, rather than transcellular,
      transport of antibodies. Kinetic studies show that initial damage caused by
      apical toxin is required for efficient neutralization by basolateral antibodies.
      These data may represent a general mechanism of humoral response-mediated
      protection against enteric pathogens. 

PMID- 25385798
TI  - Role of dendritic cells in the pathogenesis of Whipple's disease.
AB  - Accumulation of Tropheryma whipplei-stuffed macrophages in the duodenum, impaired
      T. whipplei-specific Th1 responses, and weak secretion of interleukin-12 (IL-12)
      are hallmarks of classical Whipple's disease (CWD). This study addresses
      dendritic cell (DC) functionality during CWD. We documented composition,
      distribution, and functionality of DC ex vivo or after in vitro maturation by
      fluorescence-activated cell sorting (FACS) and by immunohistochemistry in situ. A
      decrease in peripheral DC of untreated CWD patients compared to healthy donors
      was due to reduced CD11c(high) myeloid DC (M-DC). Decreased maturation markers
      CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation,
      disclosed an immature M-DC phenotype. In vitro-generated monocyte-derived DC from
      CWD patients showed normal maturation and T cell-stimulatory capacity under
      proinflammatory conditions but produced less IL-12 and failed to activate T.
      whipplei-specific Th1 cells. In duodenal and lymphoid tissues, T. whipplei was
      found within immature DC-SIGN(+) DC. DC and proliferating lymphocytes were
      reduced in lymph nodes of CWD patients compared to levels in controls. Our
      results indicate that dysfunctional IL-12 production by DC provides suboptimal
      conditions for priming of T. whipplei-specific T cells during CWD and that
      immature DC carrying T. whipplei contribute to the dissemination of the
      bacterium. 

PMID- 25385799
TI  - Neutralization of mitochondrial superoxide by superoxide dismutase 2 promotes
      bacterial clearance and regulates phagocyte numbers in zebrafish.
AB  - Mitochondria are known primarily as the location of the electron transport chain
      and energy production in cells. More recently, mitochondria have been shown to be
      signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS)
      generated as by-products of the electron transport chain within mitochondria
      significantly impact cellular signaling pathways. Because of the toxic nature of
      ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2),
      to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during
      severe infections, mitochondrial dysfunction can occur and lead to multiorgan
      failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can
      infect immunocompromised patients. Infochemicals and exotoxins associated with P.
      aeruginosa are capable of causing mitochondrial dysfunction. In this work, we
      describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish
      innate immune response to P. aeruginosa infection. sod2 is upregulated in
      mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro,
      and sod2 knockdown in zebrafish results in an increased bacterial burden. Further
      investigation revealed that phagocyte numbers are compromised in Sod2-deficient
      zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical
      MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2
      deficient zebrafish. Our work highlights the importance of mitochondrial ROS
      regulation by SOD2 in the context of innate immunity and supports the use of
      mitochondrion-targeted ROS scavengers as potential adjuvant therapies during
      severe infections. 

PMID- 25385800
TI  - Contribution of Veillonella parvula to Pseudomonas aeruginosa-mediated
      pathogenicity in a murine tumor model system.
AB  - The recent finding that high numbers of strict anaerobes are present in the
      respiratory tract of cystic fibrosis (CF) patients has drawn attention to the
      pathogenic contribution of the CF microbiome to airway disease. In this study, we
      investigated the specific interactions of the most dominant bacterial CF
      pathogen, Pseudomonas aeruginosa, with the anaerobic bacterium Veillonella
      parvula, which has been recovered at comparable cell numbers from the respiratory
      tract of CF patients. In addition to growth competition experiments,
      transcriptional profiling, and analyses of biofilm formation by in vitro studies,
      we used our recently established in vivo murine tumor model to investigate mutual
      influences of the two pathogens during a biofilm-associated infection process. We
      found that P. aeruginosa and V. parvula colonized distinct niches within the
      tumor. Interestingly, significantly higher cell numbers of P. aeruginosa could be
      recovered from the tumor tissue when mice were coinfected with both bacterial
      species than when mice were monoinfected with P. aeruginosa. Concordantly, the
      results of in vivo transcriptional profiling implied that the presence of V.
      parvula supports P. aeruginosa growth at the site of infection in the host, and
      the higher P. aeruginosa load correlated with clinical deterioration of the host.
      Although many challenges must be overcome to dissect the specific interactions of
      coinfecting bacteria during an infection process, our findings exemplarily
      demonstrate that the complex interrelations between coinfecting microorganisms
      and the immune responses determine clinical outcome to a much greater extent than
      previously anticipated. 

PMID- 25385803
TI  - Pilot study of a novel population of head and neck cancer patients in the CRN.
AB  - Head and neck cancers are challenging to study because of their relatively low
      incidence. A large, novel population of patients with head and neck cancers that
      has not been previously studied and distinct from the referral populations has
      been identified. The National Cancer Institute-funded Health Maintenance
      Organization Cancer Research Network is a consortium of 15 nonprofit research
      centers based in large, vertically integrated health care delivery organizations
      across the United States. They represent a geographically, racially, and
      socioeconomically diverse population. These community-based organizations provide
      care to approximately 10 million individuals and 57,692 patients with head and
      neck cancer. This pilot study and preliminary analysis seeks to demonstrate the
      potential this network holds as a resource for clinical cancer research and to
      identify it as a unique resource that allows for more detailed queries than are
      currently available to researchers. 

PMID- 25385801
TI  - Antibody response specific to the capsular polysaccharide is impaired in
      Streptococcus suis serotype 2-infected animals.
AB  - Streptococcus suis serotype 2 is an extracellular encapsulated bacterium that
      causes severe septicemia and meningitis in swine and humans. Albeit crucial in
      the fight against encapsulated bacteria, the nature of the capsular
      polysaccharide (CPS)-specific antibody (Ab) response during S. suis type 2
      infection is unknown. We compared for the first time the features of CPS-specific
      versus protein-specific Ab responses during experimental infections with live
      virulent S. suis type 2 in mice. The primary protein-specific Ab response was
      dominated by both type 1 and 2 IgG subclasses, whereas IgM titers were more
      modest. The secondary protein-specific Ab response showed all of the features of
      a memory response with faster kinetics and boosted the titers of all Ig isotypes.
      In contrast, the primary CPS-specific Ab response was either inexistent or had
      titers only slightly higher than those in noninfected animals and was essentially
      composed of IgM. A poor CPS-specific memory response was observed, with only a
      moderate boost in IgM titers and no IgG. Both protein- and CPS-specific Ab
      responses were Toll-like receptor 2 independent. By using S. suis type 2 strains
      of European or North American origin, the poor CPS-specific Ab response was
      demonstrated to be independent of the genotypic/phenotypic diversity of the
      strain within serotype 2. Finally, the CPS-specific Ab response was also impaired
      and lacked isotype switching in S. suis-infected pigs, the natural host of the
      bacterium. The better resistance of preinfected animals to reinfection with the
      same strain of S. suis type 2 might thus more likely be related to the
      development of a protein rather than CPS Ab response. 

PMID- 25385802
TI  - Epidemiological trends in malignant lacrimal gland tumors.
AB  - OBJECTIVE: To describe epidemiological trends in lacrimal gland malignancies in
      the United States. STUDY DESIGN: Retrospective database review. SETTING:
      Multicenter registry. SUBJECTS AND METHODS: A total of 702 malignant tumors of
      the lacrimal gland from the Surveillance, Epidemiology, and End Results database
      were included in the study. Disease-specific and overall survival were the
      primary outcome measures. Kaplan-Meier survival curves were generated for
      multiple patient and tumor characteristics, including race, histology, TNM tumor
      stage, age at diagnosis, radiotherapy, gender, and tumor grade. Cox proportional
      hazards regression was performed to assess the impact of patient and tumor
      characteristics on survival. RESULTS: Lymphoma (58.0%), adenoid cystic carcinoma
      (13.4%), adenocarcinoma (3.8%), and mucoepidermoid carcinoma (3.6%) accounted for
      most tumors. Lymphoma was associated with more favorable survival rates, while
      adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma were
      associated with worse prognosis. There was a steady increase in the proportion of
      lymphoma diagnosed since 1973. In a multivariate Cox proportional hazards
      regression model, tumor histology remained as the only covariate correlated with
      disease-specific survival. CONCLUSION: Patient characteristics and survival rates
      differ between lymphoma, adenoid cystic carcinoma, adenocarcinoma, and
      mucoepidermoid carcinoma. The proportion of lacrimal gland cancer diagnosed as
      lymphoma has steadily increased over time. Cox proportional hazards regression
      analysis demonstrated tumor histology as one of the most important factors in
      patient survival. These results augment our understanding of the expected disease
      course of lacrimal gland malignancies.

PMID- 25385804
TI  - A rare case of syphilitic mastoiditis concomitant with neurosyphilis.

PMID- 25385805
TI  - Pediatric head and neck complications of Streptococcus pneumoniae before and
      after PCV7 vaccination.
AB  - OBJECTIVE: To discuss pediatric head and neck complications of pneumococcal
      infections before and after the introduction of the PCV7 vaccine. STUDY DESIGN:
      Cross-sectional analysis of a national database. STUDY SETTING: Kids National
      Inpatient Database. METHODS: A retrospective review of the Kids National
      Inpatient Database yielded 31,738 pediatric reports involving complications of
      meningitis, mastoiditis, periorbital cellulitis, and Bezold abscesses due to
      Streptococcus pneumoniae diagnoses. Each report was analyzed for incidence,
      length of stay, mean hospital cost, and inpatient admittance from the emergency
      department. Finally, we calculated the expected annual incidence of each
      complication via variance-weighted analysis to determine the expected incidence
      if the vaccine was not administered. RESULTS: We identified a significant
      decrease in the incidence of several complications after the introduction of the
      PCV7 vaccine and also when comparing these findings to our predicted incidence
      calculations if the vaccine was not administered. Inpatient admittance from the
      emergency department for Bezold abscess, periorbital cellulitis, mastoiditis, and
      meningitis was significantly increased in the pediatric age group (ages 1-4; P <
      .05). Furthermore, there was a significant increase in the cost to provide care
      for each of the described conditions (P < .05). CONCLUSIONS: The PCV7 vaccine
      produced a measurable reduction in head and neck complications associated with S
      pneumoniae. However, our data suggest that these benefits were also met with
      increased inpatient admittance from the emergency department, hospital costs, and
      length of stay, each of which may be attributed to the selection of a more
      pathogenic subtype.

PMID- 25385806
TI  - Localized intraoperative virtual endoscopy (LIVE) for surgical guidance in 16
      skull base patients.
AB  - IMPORTANCE: Previous preclinical studies of localized intraoperative virtual
      endoscopy-image-guided surgery (LIVE-IGS) for skull base surgery suggest a
      potential clinical benefit. OBJECTIVE: The first aim was to evaluate the
      registration accuracy of virtual endoscopy based on high-resolution magnetic
      resonance imaging under clinical conditions. The second aim was to implement and
      assess real-time proximity alerts for critical structures during skull base
      drilling. DESIGN AND SETTING: Patients consecutively referred for sinus and skull
      base surgery were enrolled in this prospective case series. PARTICIPANTS: Five
      patients were used to check registration accuracy and feasibility with the
      subsequent 11 patients being treated under LIVE-IGS conditions with presentation
      to the operating surgeon (phase 2). INTERVENTION: Sixteen skull base patients
      were endoscopically operated on by using image-based navigation while LIVE-IGS
      was tested in a clinical setting. MAIN OUTCOME AND MEASURES: Workload was
      quantitatively assessed using the validated National Aeronautics and Space
      Administration Task Load Index (NASA-TLX) questionnaire. RESULTS: Real-time
      localization of the surgical drill was accurate to ~1 to 2 mm in all cases. The
      use of 3-mm proximity alert zones around the carotid arteries and optic nerve
      found regular clinical use, as the median minimum distance between the tracked
      drill and these structures was 1 mm (0.2-3.1 mm) and 0.6 mm (0.2-2.5 mm),
      respectively. No statistical differences were found in the NASA-TLX indicators
      for this experienced surgical cohort. CONCLUSIONS AND RELEVANCE: Real-time
      proximity alerts with virtual endoscopic guidance was sufficiently accurate under
      clinical conditions. Further clinical evaluation is required to evaluate the
      potential surgical benefits, particularly for less experienced surgeons or for
      teaching purposes.

PMID- 25385807
TI  - Microvascular reconstruction of segmental mandibular defects without
      tracheostomy.
AB  - OBJECTIVE: To report our experience with mandibular resection and reconstruction
      using vascularized bone-containing free flaps without an elective tracheostomy.
      STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral hospital
      center. SUBJECTS AND METHODS: Sixty-six patients undergoing mandibular
      reconstruction with vascularized bone-containing free flaps without an elective
      tracheostomy were identified between 1995 and 2013. We describe patient, tumor,
      and surgical factors and report perioperative outcomes in this population.
      RESULTS: Most patients underwent fibula free flap reconstruction (n = 61,
      92.44%). The 4 most frequent indications for resection were osteoradionecrosis,
      parotid carcinoma, oral squamous cell carcinoma, and osteomyelitis. Bone defects
      ranging from 4.0 to 13.0 cm were reconstructed, and associated soft-tissue
      defects were reconstructed with skin paddle sizes ranging from 24.0 to 450.0
      cm(2). There was only 1 patient with a bilateral central mandibular defect, and
      there were no tongue/pharyngeal soft-tissue defects or bilateral neck
      dissections. One case required emergent tracheostomy on postoperative day 1, and
      2 more patients developed respiratory complications. There were no cases of
      perioperative death or flap failure. CONCLUSION: Mandibular free flap
      reconstruction is feasible without an elective tracheostomy in a subset of
      carefully selected patients without bilateral central mandibular defects,
      tongue/pharynx defects, or bilateral neck dissection.

PMID- 25385808
TI  - Preparing for emergency: a valid, reliable assessment tool for emergency
      cricothyroidotomy skills.
AB  - OBJECTIVE: Emergency cricothyrodotomy (EC) is a lifesaving procedure. Evidence
      based assessment of training effects and competency levels is relevant to all
      departments involved in emergency airway management. As most training uses low
      fidelity models, the predictive value of good performance on such a model becomes
      relevant with regard to performance on a high-fidelity model (cadaver). This
      requires a valid assessment tool for EC performance. STUDY DESIGN: Psychometric
      study on low-fidelity models and human cadavers. SETTING: University hospital.
      SUBJECTS AND METHODS: An assessment tool was created. Sixteen physicians (7
      experienced surgeons and 9 novice physicians) performed an EC on a low-fidelity
      model and a cadaver. Two blinded raters assessed video recordings of performances
      using the assessment tool. RESULTS: We found a high interrater reliability, based
      on a Pearson's r (0.81), and good evidence for validity, based on successfully
      distinguishing the 2 groups, using an independent samples t test (P < .001). We
      found a good correlation between performance on a low-fidelity model and the
      cadaver with an R (2) = 0.78. CONCLUSION: The tool for assessing EC competence
      proved reliable and valid. Performance on a low-fidelity model measured this way
      is a good predictor of performance in a more lifelike situation.

PMID- 25385809
TI  - Test battery of cranial nerves VII and VIII for assessing herpes zoster oticus.
AB  - OBJECTIVE: This study adopted a test battery of cranial nerves (CNs) VII and VIII
      comprising a facial nerve function test, audiometry, a caloric test, and ocular
      and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP, respectively)
      tests to assess the function of CNs VII and VIII comprehensively so as to predict
      facial nerve recovery in patients with herpes zoster oticus (HZO). STUDY DESIGN:
      Case series with chart review. SETTING: University hospital. METHODS: A total of
      20 patients with HZO underwent a test battery of CNs VII and VIII. Registering
      the unaffected nerve bundles in the internal auditory canal was based on the
      number of normal results in the test battery of CNs VII and VIII. Fair facial
      nerve recovery is defined as the improvement of facial paresis to facial nerve
      grades I to II/VI. RESULTS: In 20 patients with HZO, 6, 7, 3, and 4 patients had
      0, 1, 2, and 3 unaffected nerve bundles, respectively. A significantly positive
      correlation was identified between the number of unaffected nerve bundles and
      fair facial nerve recovery. Similarly, a statistically significant predictor of
      fair facial nerve recovery was noted for unaffected nerve bundles (odds ratio,
      15.42) but not for grading of the facial nerve (odds ratio, 0.49). CONCLUSION:
      Grading of the facial nerve alone fails to predict the outcome of facial paresis
      in patients with HZO mainly because it overlooks the involvement of CN VIII.
      Alternatively, a combined test battery of CNs VII and VIII may serve as a strong
      predictor for facial nerve recovery.

PMID- 25385810
TI  - Glomus tympanicum: a review of 115 cases over 4 decades.
AB  - OBJECTIVE: To characterize the clinical presentation, surgical management, and
      outcomes of a large consecutive cohort of patients with glomus tympanicum (GT)
      tumors managed at a single tertiary referral group over 4 decades. STUDY DESIGN:
      Retrospective review. SETTING: Tertiary neurotological referral center. SUBJECTS
      AND METHODS: All patients underwent surgical treatment of histopathologically
      confirmed GT between January 1973 and March 2014. Audiometric outcomes were
      reported according to AAO-HNS guidelines, and tumor stage was described using the
      Glasscock-Jackson classification system. RESULTS: There were 115 patients (90.4%
      women; mean age, 55.2 years) who met the inclusion criteria; 38 (33.0%) cases of
      GT were stage I, 51 (44.3%) stage II, 10 (8.7%) stage III, and 16 (13.9%) stage
      IV. There were 108 (93.9%) patients who underwent gross total removal, while 7
      (6.1%) received less than complete resection for advanced disease that was
      adherent to the petrous carotid artery, facial nerve, stapes footplate, or round
      window. Two patients who underwent gross total resection experienced transient
      facial paresis, and 1 had internal carotid injury with stroke. No patients had
      been diagnosed with recurrent disease at a mean follow-up of 30.4 months.
      CONCLUSION: Surgery remains the treatment of choice for GT, providing a high rate
      of tumor control and resolution of aural symptoms with a low risk of
      complications. The surgical approach and extent of resection should be tailored
      to the patient. Gross total resection can be performed in over 90% of patients;
      however, leaving a limited adherent tumor remnant on the facial nerve or carotid
      artery should be considered with advanced infiltrative disease to prevent
      unnecessary morbidity.

PMID- 25385811
TI  - Systematic review of the quality of economic evaluations in the otolaryngology
      literature.
AB  - OBJECTIVE: To evaluate the quality of economic evaluations published in the
      otolaryngology--head and neck surgery literature, which will identify
      methodologic weaknesses that can be improved on in future studies. A secondary
      objective is to identify factors that may be associated with higher quality
      economic evaluations. DATA SOURCES: Ovid Medline (including PubMed), Embase, and
      the National Health Services Economic Evaluation databases. REVIEW METHODS: A
      systematic search was performed of the aforementioned databases according to
      PRISMA guidelines. The search was performed using otolaryngology key terms
      combined with the term cost. A manual search of 36 otolaryngology journals was
      also performed. Included studies were graded using the Quality of Health
      Economics Studies instrument, a 16-item checklist providing a total quality score
      of 100. RESULTS: Fifty studies were identified, and the mean quality rating was
      54.7/100 (SD = 30.9). The most commonly omitted methodology components were a
      lack of discussion of limitations and biases, failure to address the negative
      outcomes of examined interventions, and a lack of a robust sensitivity analysis.
      Higher quality economic evaluations were associated with a higher journal impact
      factor (correlation coefficient r = 0.62, P = .0001), having an author with a PhD
      in health economics (r = 0.56, P = .0001), and having authors who have published
      prior economic evaluations (r = 0.46, P = .001). CONCLUSION: Results from this
      study have demonstrated that there are several methodological domains that can be
      improved on when publishing economic evaluations in the otolaryngology
      literature. Authors should follow recommended methodological and reporting
      guidelines to optimize the transparency and accuracy of the overall conclusions.

PMID- 25385813
TI  - Contemporary reviews in toxicology.

PMID- 25385814
TI  - The impact factor continues its rise: good news from the European Journal of
      Cardio-Thoracic Surgery-3.048.

PMID- 25385815
TI  - Clinical Decision Support for Early Recognition of Sepsis.
AB  - Sepsis is an inflammatory response triggered by infection, with a high in
      hospital mortality rate. Early recognition and treatment can reverse the
      inflammatory response, with evidence of improved patient outcomes. One challenge
      clinicians face is identifying the inflammatory syndrome against the background
      of the patient's infectious illness and comorbidities. An approach to this
      problem is implementation of computerized early warning tools for sepsis. This
      multicenter retrospective study sought to determine clinimetric performance of a
      cloud-based computerized sepsis clinical decision support system (CDS),
      understand the epidemiology of sepsis, and identify opportunities for quality
      improvement. Data encompassed 6200 adult hospitalizations from 2012 through 2013.
      Of 13% patients screened-in, 51% were already suspected to have an infection when
      the system activated. This study focused on a patient cohort screened-in before
      infection was suspected; median time from arrival to CDS activation was 3.5
      hours, and system activation to diagnostic collect was another 8.6 hours. 

PMID- 25385816
TI  - Usefulness of the Logistic Clinical Syntax Score in Prediction of Saphenous Vein
      Graft Failure in Patients Undergoing Coronary Artery Bypass Grafting.
AB  - We investigated the association between the preoperative logistic clinical syntax
      score (log CSS), saphenous vein graft (SVG) patency, and major adverse cardiac
      and cerebrovascular events (MACCEs) after coronary artery bypass surgery (CABG).
      Of 1875 patients undergoing isolated CABG between 2009 and 2011, 267 patients,
      who later underwent coronary angiography, were included in the study. The primary
      end point was at least 1 graft occlusion on the follow-up coronary angiogram. The
      secondary end point was a composite of MACCE. In multivariate analysis, log CSS
      was found as a strong predictor of SVG failure (odds ratio [OR] 0.66, 95%
      confidence interval [CI]: 0.46-0.94, P = .02; and OR: 2.21, 95% CI: 1.02-4.75, P
      = .04, respectively): log CSS was also associated with MACCE (P = .001 and P <
      .001, respectively). The addition of clinical parameters to the anatomical SYNTAX
      score, termed as "log CSS", augmented the accuracy and reliability of the
      prediction of SVG failure and MACCE in patients undergoing CABG. 

PMID- 25385817
TI  - GEP-NETS update: Interventional radiology: role in the treatment of liver
      metastases from GEP-NETs.
AB  - Neuroendocrine tumors from gastro-pancreatic origin (GEP-NET) can be responsible
      for liver metastases. Such metastases can be the dominant part of the disease as
      well due to the tumor burden itself or the symptoms related to such liver
      metastases. Intra-arterial therapies are commonly used in liver only or liver
      dominant disease and encompass trans-arterial chemoembolization (TACE), trans
      arterial embolization (TAE), and radioembolization (RE). TACE performed with drug
      emulsified in Lipiodol has been used for the past 20 years with reported overall
      survival in the range of 3-4 years, with objective response up to 75%. Response
      to TACE is higher when treatment is used as a first-line therapy and degree of
      liver involvement is lower. Benefit of TACE over TAE is unproven in randomized
      study, but reported in retrospective studies namely in pancreatic NETs. RE
      provides early interesting results that need to be further evaluated in terms of
      benefit and toxicity. Radiofrequency ablation allows control of small size and
      numbered liver metastases, with low invasiveness. Ideal metastases to target are
      one metastasis <5 cm, or three metastases <3 cm, or a sum of diameter of all
      metastases below 8 cm. Ablation therapies can be applied in the lung or in the
      bones when needed, and more invasive surgery should be probably saved for large
      size metastases. Even if the indication of image-guided therapy in the treatment
      of GEP-NET liver metastases needs to be refined, such therapies allow for
      manageable invasive set of treatments able to address oligometastatic patients in
      liver, lung, and bones. These treatments applied locally will save the benefit
      and the toxicity of systemic therapy for more advanced stage of the disease.

PMID- 25385818
TI  - Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with
      acromegaly: association with clinical presentation and response to treatments.
AB  - OBJECTIVE: IGF1 and IGFBP3 gene polymorphisms have been recently described.
      However, their potential role in the setting of acromegaly and its outcome is
      unknown. In this study, we analyze these polymorphisms in patients with
      acromegaly and investigate their association with clinical presentation and
      response to treatments. DESIGN: A retrospective observational study was conducted
      in patients with acromegaly to analyze IGF1 and IGFBP3 gene polymorphisms.
      METHODS: A total of 124 patients with acromegaly (57.3% women, mean age 44.9+/
      13.1 years old) were followed up for a period of 11.4+/-8.0 years in eight
      tertiary referral hospitals in Spain. Clinical and analytical data were evaluated
      at baseline and after treatment. IGF1 and IGFBP3 gene polymorphisms were analyzed
      using PCR and specific primers. RESULTS: Baseline laboratory test results were GH
      19.3 (8.0-39.6) ng/ml, nadir GH 11.8 (4.1-21.5) ng/ml, and index IGF1 2.65+/-1.25
      upper limit of normal. Regarding the IGF1 gene polymorphism, we did not find any
      association between the number of cyto-adenosine (CA) repeats and patients'
      baseline characteristics. Nevertheless, a trend for higher nadir GH values was
      observed in patients with <19 CA repeats. Regarding the IGFBP3 polymorphism, the
      absence of an A allele at the -202 position was associated with a higher baseline
      IGF1 and a higher prevalence of cancer and polyps. There were no differences in
      response to therapies according to the specific genotypes. CONCLUSIONS:
      Polymorphisms in the IGF1 and IGFBP3 genes may not be invariably determinant of
      treatment outcome in acromegalic patients, but they may be associated with higher
      nadir GH levels or baseline IGF1, and determine a higher rate of colorectal
      polyps and cancer.

PMID- 25385819
TI  - TRAM is required for TLR2 endosomal signaling to type I IFN induction.
AB  - Detection of microbes by TLRs on the plasma membrane leads to the induction of
      proinflammatory cytokines such as TNF-alpha, via activation of NF-kappaB.
      Alternatively, activation of endosomal TLRs leads to the induction of type I IFNs
      via IFN regulatory factors (IRFs). TLR4 signaling from the plasma membrane to NF
      kappaB via the Toll/IL-1R (TIR) adaptor protein MyD88 requires the TIR sorting
      adaptor Mal, whereas endosomal TLR4 signaling to IRF3 via the TIR domain
      containing adaptor-inducing IFN-beta (TRIF) requires the TRIF-related adaptor
      molecule (TRAM). Similar to TLR4 homodimers, TLR2 heterodimers can also induce
      both proinflammatory cytokines and type I IFNs. TLR2 plasma membrane signaling to
      NF-kappaB is known to require MyD88 and Mal, whereas endosomal IRF activation by
      TLR2 requires MyD88. However, it was unclear whether TLR2 requires a sorting
      adaptor for endosomal signaling, like TLR4 does. In this study, we show that TLR2
      dependent IRF7 activation at the endosome is both Mal- and TRAM-dependent, and
      that TRAM is required for the TLR2-dependent movement of MyD88 to endosomes
      following ligand engagement. TRAM interacted with both TLR2 and MyD88, suggesting
      that TRAM can act as a bridging adapter between these two molecules. Furthermore,
      infection of macrophages lacking TRAM with herpes viruses or the bacterium
      Staphylococcus aureus led to impaired induction of type I IFN, indicating a role
      for TRAM in TLR2-dependent responses to human pathogens. Our work reveals that
      TRAM acts as a sorting adaptor not only for TLR4, but also for TLR2, to
      facilitate signaling to IRF7 at the endosome, which explains how TLR2 is capable
      of causing type I IFN induction. 

PMID- 25385820
TI  - STING-mediated DNA sensing promotes antitumor and autoimmune responses to dying
      cells.
AB  - Adaptive immune responses to Ags released by dying cells play a critical role in
      the development of autoimmunity, allograft rejection, and spontaneous as well as
      therapy-induced tumor rejection. Although cell death in these situations is
      considered sterile, various reports have implicated type I IFNs as drivers of the
      ensuing adaptive immune response to cell-associated Ags. However, the mechanisms
      that underpin this type I IFN production are poorly defined. In this article, we
      show that dendritic cells (DCs) can uptake and sense nuclear DNA-associated
      entities released by dying cells to induce type I IFN. Remarkably, this molecular
      pathway requires STING, but not TLR or NLR function, and results in the
      activation of IRF3 in a TBK1-dependent manner. DCs are shown to depend on STING
      function in vivo to efficiently prime IFN-dependent CD8(+) T cell responses to
      tumor Ags. Furthermore, loss of STING activity in DCs impairs the generation of
      follicular Th cells and plasma cells, as well as anti-nuclear Abs, in an
      inducible model of systemic lupus erythematosus. These findings suggest that the
      STING pathway could be manipulated to enable the rational design of
      immunotherapies that enhance or diminish antitumor and autoimmune responses,
      respectively. 

PMID- 25385821
TI  - Chemokine-mediated B cell trafficking during early rabbit GALT development.
AB  - Microbial and host cell interactions stimulate rabbit B cells to diversify the
      primary Ab repertoire in GALT. B cells at the base of appendix follicles begin
      proliferating and diversifying their V-(D)-J genes around 1 wk of age, ~5 d after
      B cells first begin entering appendix follicles. To gain insight into the
      microbial and host cell interactions that stimulate B cells to diversify the
      primary Ab repertoire, we analyzed B cell trafficking within follicles during the
      first week of life. We visualized B cells, as well as chemokines that mediate B
      cell homing in lymphoid tissues, by in situ hybridization, and we examined B cell
      chemokine receptor expression by flow cytometry. We found that B cells were
      activated and began downregulating their BCRs well before a detectable B cell
      proliferative region appeared at the follicle base. The proliferative region was
      similar to germinal center dark zones, in that it exhibited elevated CXCL12 mRNA
      expression, and B cells that upregulated CXCR4 mRNA in response to signals
      acquired from selected intestinal commensals localized in this region. Our
      results suggest that after entering appendix follicles, B cells home sequentially
      to the follicle-associated epithelium, the follicular dendritic cell network, the
      B cell/T cell boundary, and, ultimately, the base of the follicle, where they
      enter a proliferative program and diversify the primary Ab repertoire. 

PMID- 25385822
TI  - Chloroquine promotes IL-17 production by CD4+ T cells via p38-dependent IL-23
      release by monocyte-derived Langerhans-like cells.
AB  - Recent studies suggest a role for autophagy in the secretion of IL-1 cytokines
      regulating the development of inflammatory diseases. The antimalarial drug and
      autophagy/lysosome inhibitor chloroquine (CHQ) is considered as potential trigger
      of drug-induced or drug-aggravated psoriasis, in which Th17 cells sustain a
      persistent inflammation. In this study, we investigated the effect of CHQ on
      human monocyte-derived Langerhans-like cells (MoLC) and dendritic cells (MoDC) in
      response to IL-1beta. The presence of CHQ reduced IL-12p70 release in both
      subsets, but surprisingly increased IL-6 production in MoDC and IL-23 in MoLC.
      Importantly, CHQ-treated MoLC promoted IL-17A secretion by CD4(+) T cells and
      elevated RORC mRNA levels, whereas IFN-gamma release was reduced. The
      dysregulation of IL-12 family cytokines in MoLC and MoDC occurred at the
      transcriptional level. Similar effects were obtained with other late autophagy
      inhibitors, whereas PI3K inhibitor 3-methyladenine failed to increase IL-23
      secretion. The modulated cytokine release was dependent on IL-1 cytokine
      activation and abrogated by a specific IL-1R antagonist. CHQ elevated expression
      of TNFR-associated factor 6, a common intermediate in IL-1R and TLR-dependent
      signaling. Accordingly, treatment with Pam3CSK4 and CHQ enhanced IL-23 release in
      MoLC and MoDC. CHQ inhibited autophagic flux, confirmed by increased LC3-II and
      p62 expression, and activated ERK, p38, and JNK MAPK, but only inhibition of p38
      abrogated IL-23 release by MoLC. Thus, our findings indicate that CHQ modulates
      cytokine release in a p38-dependent manner, suggesting an essential role of
      Langerhans cells and dendritic cells in CHQ-provoked psoriasis, possibly by
      promoting Th17 immunity. 

PMID- 25385823
TI  - Pig skin includes dendritic cell subsets transcriptomically related to human CD1a
      and CD14 dendritic cells presenting different migrating behaviors and T cell
      activation capacities.
AB  - Swine skin is one of the best structural models for human skin, widely used to
      probe drug transcutaneous passage and to test new skin vaccination devices.
      However, little is known about its composition in immune cells, and among them
      dendritic cells (DC), that are essential in the initiation of the immune
      response. After a first seminal work describing four different DC subpopulations
      in pig skin, we hereafter deepen the characterization of these cells, showing the
      similarities between swine DC subsets and their human counterparts. Using
      comparative transcriptomic study, classical phenotyping as well as in vivo and in
      vitro functional studies, we show that swine CD163(pos) dermal DC (DDC) are
      transcriptomically similar to the human CD14(pos) DDC. CD163(pos) DDC are
      recruited in inflamed skin, they migrate in inflamed lymph but they are not
      attracted toward CCL21, and they modestly activate allogeneic CD8 T cells. We
      also show that CD163(low) DDC are transcriptomically similar to the human
      CD1a(pos) DDC. CD163(low) DDC migrate toward CCL21, they activate allogeneic CD8
      and CD4 T cells and, like their potential human lung counterpart, they skew CD4 T
      cells toward a Th17 profile. We thus conclude that swine skin is a relevant model
      for human skin vaccination. 

PMID- 25385824
TI  - IgG4 and IgE transcripts in childhood allergic asthma reflect divergent antigen
      driven selection.
AB  - The physiologic function of the "odd" Ab IgG4 remains enigmatic. IgG4 mediates
      immunotolerance, as, for example, during specific immunotherapy of allergies, but
      it mediates tissue damage in autoimmune pemphigus vulgaris and "IgG4-related
      disease." Approximately half of the circulating IgG4 molecules are bispecific
      owing to their unique ability to exchange half-molecules. Better understanding of
      the interrelation between IgG4 and IgE repertoires may yield insight into the
      pathogenesis of allergies and into potential novel therapies that modulate IgG4
      responses. We aimed to compare the selective forces that forge the IgG4 and IgE
      repertoires in allergic asthma. Using an IgG4-specific RT-PCR, we amplified,
      cloned, and sequenced IgG4 H chain transcripts of PBMCs from 10 children with
      allergic asthma. We obtained 558 functional IgG4 sequences, of which 286 were
      unique. Compared with previously published unique IgE transcripts from the same
      blood samples, the somatic mutation rate was significantly enhanced in IgG4
      transcripts (62 versus 83%; p < 0.001), whereas fewer IgG4 sequences displayed
      statistical evidence of Ag-driven selection (p < 0.001). On average, the
      hypervariable CDRH3 region was four nucleotides shorter in IgG4 than in IgE
      transcripts (p < 0.001). IgG4 transcripts in the circulation of children with
      allergic asthma reflect some characteristics of classical Ag-driven B2 immune
      responses but display less indication of Ag selection than do IgE transcripts.
      Although allergen-specific IgG4 can block IgE-mediated allergen presentation and
      degranulation of mast cells, key factors that influence the Ag-binding properties
      of the Ab differ between the overall repertoires of circulating IgG4- and IgE
      expressing cells. 

PMID- 25385826
TI  - Feasibility of a patient-centered deprescribing process to reduce inappropriate
      use of proton pump inhibitors.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are inappropriately prescribed in up to
      50% of users. Systematic medication review and cessation of inappropriate
      medications or deprescribing may improve patient outcomes and reduce costs.
      OBJECTIVE: The aim of this study was to assess the feasibility of a patient
      centered deprescribing process in a population of adults with complex
      polypharmacy. METHODS: This was a prospective feasibility study. Participants
      were recruited from hospital outpatient clinics. The patient-centered
      deprescribing process consisted of 5 steps: comprehensive medication history,
      identification of potentially inappropriate medications, determining if the
      medication can be ceased, planning the withdrawal regimen (eg, tapering where
      necessary), and provision of monitoring, support, and documentation. Feasibility
      was determined by assessing time taken to complete the different steps of the
      deprescribing process and participant feedback. RESULTS: In all, 57 PPI users
      were recruited; participants were 70 +/- 14 years old and took 14 +/- 6
      medications. The indication for PPI use was verified in 43 participants and
      judged as potentially inappropriate in 19 (44%); 8 were suitable for trial
      withdrawal, and 6 consented. All 6 successfully ceased (n = 3) or reduced (n = 3)
      their PPI use, and this was sustained at 6 months postintervention in 4
      participants. CONCLUSIONS: The patient-centered deprescribing process can safely
      reduce inappropriate PPI prescribing in a small proportion of people. Although
      the process was acceptable to participants, difficulties in accessing complete
      medical histories, time limitations, and minimal evidence to support
      effectiveness in certain indications were barriers to implementation of the
      process in clinical practice.

PMID- 25385825
TI  - Infiltrating regulatory B cells control neuroinflammation following viral brain
      infection.
AB  - Previous studies have demonstrated the existence of a subset of B lymphocytes,
      regulatory B cells (Bregs), which modulate immune function. In this study, in
      vivo and in vitro experiments were undertaken to elucidate the role of these
      Bregs in controlling neuroinflammation following viral brain infection. We used
      multicolor flow cytometry to phenotype lymphocyte subpopulations infiltrating the
      brain, along with in vitro cocultures to assess their anti-inflammatory and
      immunoregulatory roles. This distinctive subset of CD19(+)CD1d(hi)CD5(+) B cells
      was found to infiltrate the brains of chronically infected animals, reaching
      highest levels at the latest time point tested (30 d postinfection). B cell
      deficient Jh(-/-) mice were found to develop exacerbated neuroimmune responses as
      measured by enhanced accumulation and/or retention of CD8(+) T cells within the
      brain, as well as increased levels of microglial activation (MHC class II).
      Conversely, levels of Foxp3(+) regulatory T cells were found to be significantly
      lower in Jh(-/-) mice when compared with wild-type (Wt) animals. Further
      experiments showed that in vitro-generated IL-10-secreting Bregs (B10) were able
      to inhibit cytokine responses from microglia following stimulation with viral
      Ags. These in vitro-generated B10 cells were also found to promote proliferation
      of regulatory T cells in coculture studies. Finally, gain-of-function experiments
      demonstrated that reconstitution of Wt B cells into Jh(-/-) mice restored
      neuroimmune responses to levels exhibited by infected Wt mice. Taken together,
      these results demonstrate that Bregs modulate T lymphocyte as well as microglial
      cell responses within the infected brain and promote CD4(+)Foxp3(+) T cell
      proliferation in vitro. 

PMID- 25385828
TI  - Evolution, current status, and way forward for the Asian Oceanian Association of
      Neurology.

PMID- 25385827
TI  - Upregulation of ABC transporters contributes to chemoresistance of sphingosine 1
      phosphate lyase-deficient fibroblasts.
AB  - Sphingosine 1-phosphate (S1P) is an extra- and intracellular mediator that
      regulates cell growth, survival, migration, and adhesion in many cell types. S1P
      lyase is the enzyme that irreversibly cleaves S1P and thereby constitutes the
      ultimate step in sphingolipid catabolism. It has been reported previously that
      embryonic fibroblasts from S1P lyase-deficient mice (Sgpl1(-/-)-MEFs) are
      resistant to chemotherapy-induced apoptosis through upregulation of B cell
      lymphoma 2 (Bcl-2) and Bcl-2-like 1 (Bcl-xL). Here, we demonstrate that the
      transporter proteins Abcc1/MRP1, Abcb1/MDR1, Abca1, and spinster-2 are
      upregulated in Sgpl1(-/-)-MEFs. Furthermore, the cells efficiently sequestered
      the substrates of Abcc1 and Abcb1, fluo-4 and doxorubicin, in subcellular
      compartments. In line with this, Abcb1 was localized mainly at intracellular
      vesicular structures. After 16 h of incubation, wild-type MEFs had small
      apoptotic nuclei containing doxorubicin, whereas the nuclei of Sgpl1(-/-)-MEFs
      appeared unchanged and free of doxorubicin. A combined treatment with the
      inhibitors of Abcb1 and Abcc1, zosuquidar and MK571, respectively, reversed the
      compartmentalization of doxorubicin and rendered the cells sensitive to
      doxorubicin-induced apoptosis. It is concluded that upregulation of multidrug
      resistance transporters contributes to the chemoresistance of S1P lyase-deficient
      MEFs. 

PMID- 25385829
TI  - IgG4-related diffuse perineural disease.

PMID- 25385830
TI  - Damping of monocular pendular nystagmus with vibration in a patient with multiple
      sclerosis.

PMID- 25385831
TI  - Aldehyde dehydrogenase variation enhances effect of pesticides associated with
      Parkinson disease.

PMID- 25385833
TI  - Teaching neuroImages: Magnetic resonance susceptibility effect for acute isolated
      cortical vein thrombosis.

PMID- 25385834
TI  - Teaching neuroImages: Hyperdense posterior cerebral artery sign.

PMID- 25385835
TI  - RBM14 prevents assembly of centriolar protein complexes and maintains mitotic
      spindle integrity.
AB  - Formation of a new centriole adjacent to a pre-existing centriole occurs only
      once per cell cycle. Despite being crucial for genome integrity, the mechanisms
      controlling centriole biogenesis remain elusive. Here, we identify RBM14 as a
      novel suppressor of assembly of centriolar protein complexes. Depletion of RBM14
      in human cells induces ectopic formation of centriolar protein complexes through
      function of the STIL/CPAP complex. Intriguingly, the formation of such structures
      seems not to require the cartwheel structure that normally acts as a scaffold for
      centriole formation, whereas they can retain pericentriolar material and
      microtubule nucleation activity. Moreover, we find that, upon RBM14 depletion, a
      part of the ectopic centriolar protein complexes in turn assemble into structures
      more akin to centrioles, presumably by incorporating HsSAS-6, a cartwheel
      component, and cause multipolar spindle formation. We further demonstrate that
      such structures assemble in the cytoplasm even in the presence of pre-existing
      centrioles. This study sheds light on the possibility that ectopic formation of
      aberrant structures related to centrioles may contribute to genome instability
      and tumorigenesis. 

PMID- 25385836
TI  - Chronic exposure to TGFbeta1 regulates myeloid cell inflammatory response in an
      IRF7-dependent manner.
AB  - Tissue microenvironment influences the function of resident and infiltrating
      myeloid-derived cells. In the central nervous system (CNS), resident microglia
      and freshly recruited infiltrating monocyte-derived macrophages (mo-MPhi) display
      distinct activities under pathological conditions, yet little is known about the
      microenvironment-derived molecular mechanism that regulates these differences.
      Here, we demonstrate that long exposure to transforming growth factor-beta1
      (TGFbeta1) impaired the ability of myeloid cells to acquire a resolving anti
      inflammatory phenotype. Using genome-wide expression analysis and chromatin
      immunoprecipitation followed by next-generation sequencing, we show that the
      capacity to undergo pro- to anti-inflammatory (M1-to-M2) phenotype switch is
      controlled by the transcription factor interferon regulatory factor 7 (IRF7) that
      is down-regulated by the TGFbeta1 pathway. RNAi-mediated perturbation of Irf7
      inhibited the M1-to-M2 switch, while IFNbeta1 (an IRF7 pathway activator)
      restored it. In vivo induction of Irf7 expression in microglia, following spinal
      cord injury, reduced their pro-inflammatory activity. These results highlight the
      key role of tissue-specific environmental factors in determining the fate of
      resident myeloid-derived cells under both physiological and pathological
      conditions. 

PMID- 25385838
TI  - The Utility of the Sino-Nasal Outcome Test (SNOT) as a Treatment Outcome Measure
      in Nonsinogenic Facial Pain Syndrome.
AB  - INTRODUCTION: The purpose of this study was to assess the strength of correlation
      between the Sino-Nasal Outcome Test (SNOT) subdomains to determine which bore the
      greatest disease burden so that it could be used as a suitable measure of
      clinical response. METHODS: Prospective clinical audit of patients attending the
      Liverpool Multi-Disciplinary Facial Pain Clinic. The Brief Pain Inventory-Facial
      (BPI-F) was used as a comparator and surrogate measure of quality of life.
      RESULTS: Fifty patients (38 female) were reviewed, of whom 66% had midfacial
      segment pain. The total SNOT score was highly correlated with the BPI-F. Both the
      sleep function and psychological issues were the most highly correlated SNOT
      subdomains with the BPI-F, followed by ear-facial symptoms. The rhinologic
      symptom subdomain had a weak correlation with the BPI-F. The total SNOT score was
      most significantly correlated with the sleep function and psychological issues
      subdomains. CONCLUSION: This study supports the utility of the SNOT questionnaire
      as a measure of clinical outcome for nonsinogenic facial pain. The total SNOT
      score is highly correlated with the BPI-F, which has been used as a surrogate
      measure of quality of life. In addition, the sleep function and psychological
      issues subdomains are suitable variables to measure response to treatment.

PMID- 25385837
TI  - Deletion of the von Hippel-Lindau gene causes sympathoadrenal cell death and
      impairs chemoreceptor-mediated adaptation to hypoxia.
AB  - Mutations of the von Hippel-Lindau (VHL) gene are associated with
      pheochromocytomas and paragangliomas, but the role of VHL in sympathoadrenal
      homeostasis is unknown. We generated mice lacking Vhl in catecholaminergic cells.
      They exhibited atrophy of the carotid body (CB), adrenal medulla, and sympathetic
      ganglia. Vhl-null animals had an increased number of adult CB stem cells,
      although the survival of newly generated neuron-like glomus cells was severely
      compromised. The effects of Vhl deficiency were neither prevented by
      pharmacological inhibition of prolyl hydroxylases or selective genetic down
      regulation of prolyl hydroxylase-3, nor phenocopied by hypoxia inducible factor
      overexpression. Vhl-deficient animals appeared normal in normoxia but survived
      for only a few days in hypoxia, presenting with pronounced erythrocytosis,
      pulmonary edema, and right cardiac hypertrophy. Therefore, in the normal
      sympathoadrenal setting, Vhl deletion does not give rise to tumors but impairs
      development and plasticity of the peripheral O2-sensing system required for
      survival in hypoxic conditions.

PMID- 25385839
TI  - Postoperative hemorrhage after transoral oropharyngectomy for cancer of the
      lateral oropharynx.
AB  - OBJECTIVE: Assessment of incidence, risk factors, management, and outcome of
      postoperative hemorrhage after transoral oropharyngectomy for cancer of the
      lateral oropharynx. METHODS: Retrospective review of a cohort of 514 cancers of
      the lateral oropharynx consecutively resected. RESULTS: Incidence of
      postoperative hemorrhage was 3.6%. In 31.5% of cases, onset was after hospital
      discharge. No hemorrhages occurred after the end of the fourth postoperative
      week. Variables associated with increased risk of hemorrhage were advanced age
      (P=.004), antithrombotic treatment (P=.012), and robotic assistance (P=.009).
      When the source of hemorrhage could be identified, hemostasis, performed
      transorally in most cases, was highly effective; no patients in this subgroup
      showed recurrence. In spontaneously resolved hemorrhage under observation or when
      no active site of bleeding was found on exploration under general anesthesia, the
      recurrence rate was 18.1%. Overall, hemorrhage resulted in death in 2 patients.
      CONCLUSION: Exploration under general anesthesia in case of active bleeding and
      observation with discussion of arterial exploration of the ipsilateral external
      carotid system in patients in whom no source of bleeding can be identified are
      the keys to successful management of this potentially lethal complication.

PMID- 25385840
TI  - Otolaryngologic surgeries are frequent in children with eosinophilic esophagitis.
AB  - OBJECTIVE: The aim was to study the prevalence of otolaryngologic surgeries in
      pediatric patients with eosinophilic esophagitis (EoE). METHODS: Retrospective
      cohort study at a tertiary care center. The type of otolaryngologic surgeries
      performed in patients with diagnosis of EoE was recorded during a 5-year period.
      RESULTS: Seventy-five percent of patients were male, with average age of EoE
      diagnosis at 7.5 years with an 83% incidence of atopy. Cohort analysis revealed
      that 33% (119/362) had a total of 275 otolaryngologic surgeries. Surgeries
      performed on 119 patients are as follows: 20% bilateral myringotomy with tubes,
      14% tonsillectomy, 18.5% adenoidectomy, 1.4% sinus irrigation, 3.3% bronchoscopy,
      and 1.4% laryngotracheoplasty (LTP); 63% of patients underwent multiple
      procedures. Thirty percent of patients undergoing bilateral myringotomy with tube
      placement (BMT) needed additional tubes. Four of 5 LTP patients had successful
      operations. Twelve percent of patients had EoE diagnosis prior to an
      otolaryngologic surgery. CONCLUSION: Thirty-three percent of children with EoE
      required otolaryngologic surgical intervention and nearly one-third who underwent
      BMT required additional ear tubes. A large fraction of children with EoE will
      undergo an otolaryngologic surgery, only a minority with a preoperative EoE
      diagnosis. Until the nature of this relationship is clarified, the high
      coincidence with otolaryngologic surgeries dictates that otolaryngologists should
      be familiar with diagnosis of EoE in patients.

PMID- 25385841
TI  - Outcomes of recurrent facial palsy in Melkersson Rosenthal syndrome.
AB  - OBJECTIVE: The objective of the study was to investigate outcomes of recurrent
      facial palsy in Melkersson Rosenthal syndrome (MRS). METHODS: We carried out a
      prospective investigation on patients who had recurrent facial palsy in MRS and
      visited an outpatient department of otolaryngology from January 2002 to January
      2012, focusing on their facial nerve outcomes. They were followed up for 12
      months. The patients who visited our department due to recurrent Bell's palsy
      during the same period were selected as controls. Oral prednisolone alone was
      given to each patient. RESULTS: A total of 22 patients with recurrent facial
      palsy in MRS and 73 patients with recurrent Bell's palsy were included in the
      study. Twelve months later, only 3 of 22 patients (13.6%) who had recurrent
      facial palsy in MRS recovered to House-Brackmann grade I, whereas 52 of 73
      patients (71.2%) who had recurrent Bell's palsy recovered completely. The
      difference was statistically significant (P<.01). CONCLUSION: Compared to
      recurrent Bell's palsy, recurrent facial palsy in MRS had much worse prognosis.

PMID- 25385842
TI  - Hyperinsulinemia induces hepatic iron overload by increasing liver TFR1 via the
      PI3K/IRP2 pathway.
AB  - Dysmetabolic iron overload syndrome (DIOS) is frequently observed, but the
      underlying mechanism remains unclear. We propose the hypothesis that
      hyperinsulinemia, a common characteristic of DIOS, may stimulate liver
      transferrin receptor 1 (TFR1) expression via the PI3K/iron regulatory protein 2
      (IRP2) pathway, leading to the occurrence of DIOS. The hepatic iron content,
      serum iron parameters, and expressions of TFRs and IRPs in the liver were
      determined in rats with temporary or long-lasting hyperinsulinemia induced by
      acute or chronic administration of insulin. The effect of insulin on TFR1
      expression and its molecular mechanism were determined in HL-7702 cells in vitro.
      It was found that long-lasting hyperinsulinemia significantly increased TFR1
      expression in the liver and induced mild-to-moderate hepatic iron overload, which
      was accompanied by a normal level of serum iron. Insulin markedly upregulated
      both protein and mRNA levels of TFR1 in HL-7702 cells. The stability of TFR1 mRNA
      stability, together with expression of IRPs expression, were both significantly
      increased by insulin treatment. Insulin-induced TFR1 expression was blocked by
      IRP2, but not by IRP1 interference, and disappeared when HL-7702 cells were
      pretreated with LY294002, triciribine hydrate, or rapamycin. In conclusion, the
      findings of this study indicate that hyperinsulnemia could induce hepatic iron
      overload by upregulating liver TFR1 via the PI3K/AKT/mTOR/IRP2 pathway, which may
      be one of the main reasons for the occurrence of DIOS. 

PMID- 25385843
TI  - beta-cell regeneration and differentiation: how close are we to the 'holy grail'?
AB  - Diabetes can be managed by careful monitoring of blood glucose and timely
      delivery of exogenous insulin. However, even with fastidious compliance, people
      with diabetes can suffer from numerous complications including atherosclerosis,
      retinopathy, neuropathy, and kidney disease. This is because delivery of
      exogenous insulin coupled with glucose monitoring cannot provide the fine level
      of glucose control normally provided by endogenous beta-cells in the context of
      intact islets. Moreover, a subset of people with diabetes lack awareness of
      hypoglycemic events; a status that can have grave consequences. Therefore, much
      effort has been focused on replacing lost or dysfunctional beta-cells with cells
      derived from other sources. The advent of stem cell biology and cellular
      reprogramming strategies have provided impetus to this work and raised hopes that
      a beta-cell replacement therapy is on the horizon. In this review, we look at two
      components that will be required for successful beta-cell replacement therapy: a
      reliable and safe source of beta-cells and a mechanism by which such cells can be
      delivered and protected from host immune destruction. Particular attention is
      paid to insulin-producing cells derived from pluripotent stem cells because this
      platform addresses the issue of scale, one of the more significant hurdles
      associated with potential cell-based therapies. We also review methods for
      encapsulating transplanted cells, a technique that allows grafts to evade immune
      attack and survive for a long term in the absence of ongoing immunosuppression.
      In surveying the literature, we conclude that there are still several substantial
      hurdles that need to be cleared before a stem cell-based beta-cell replacement
      therapy for diabetes becomes a reality. 

PMID- 25385844
TI  - Prognosis of patients with bilateral fixed dilated pupils secondary to traumatic
      extradural or subdural haematoma who undergo surgery: a systematic review and
      meta-analysis.
AB  - PRIMARY OBJECTIVE: To review the prognosis of patients with bilateral fixed and
      dilated pupils secondary to traumatic extradural (epidural) or subdural haematoma
      who undergo surgery. METHODS: A systematic review and meta-analysis was performed
      using random effects models. The Cochrane Central Register of Controlled Trials
      and PubMed databases were searched to identify relevant publications. Eligible
      studies were publications that featured patients with bilateral fixed and dilated
      pupils who underwent surgical evacuation of traumatic extra-axial haematoma, and
      reported on the rate of favourable outcome (Glasgow Outcome Score 4 or 5).
      RESULTS: Five cohort studies met the inclusion criteria, collectively reporting
      the outcome of 82 patients. In patients with extradural haematoma, the mortality
      rate was 29.7% (95% CI 14.7% to 47.2%) with a favourable outcome seen in 54.3%
      (95% CI 36.3% to 71.8%). In patients with acute subdural haematoma, the mortality
      rate was 66.4% (95% CI 50.5% to 81.9%) with a favourable outcome seen in 6.6%
      (95% CI 1.8% to 14.1%). CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Despite the
      poor overall prognosis of patients with closed head injury and bilateral fixed
      and dilated pupils, our findings suggest that a good recovery is possible if an
      aggressive surgical approach is taken in selected cases, particularly those with
      extradural haematoma. TRIAL REGISTRATION NUMBER: CRD42013005198.

PMID- 25385849
TI  - Tubulovascular cross-talk by vascular endothelial growth factor a maintains
      peritubular microvasculature in kidney.
AB  - Vascular endothelial growth factor A (VEGFA) production by podocytes is critical
      for glomerular endothelial health. VEGFA is also expressed in tubular epithelial
      cells in kidney; however, its physiologic role in the tubule has not been
      established. Using targeted transgenic mouse models, we found that Vegfa is
      expressed by specific epithelial cells along the nephron, whereas expression of
      its receptor (Kdr/Vegfr2) is largely restricted to adjacent peritubular
      capillaries. Embryonic deletion of tubular Vegfa did not affect systemic Vegfa
      levels, whereas renal Vegfa abundance was markedly decreased. Excision of Vegfa
      from renal tubules resulted in the formation of a smaller kidney, with a striking
      reduction in the density of peritubular capillaries. Consequently, elimination of
      tubular Vegfa caused pronounced polycythemia because of increased renal
      erythropoietin (Epo) production. Reducing hematocrit to normal levels in tubular
      Vegfa-deficient mice resulted in a markedly augmented renal Epo production,
      comparable with that observed in anemic wild-type mice. Here, we show that
      tubulovascular cross-talk by Vegfa is essential for maintenance of peritubular
      capillary networks in kidney. Disruption of this communication leads to increased
      renal Epo production and resulting polycythemia, presumably to counterbalance
      microvascular losses. 

PMID- 25385850
TI  - Tubular vascular endothelial growth factor-a, erythropoietin, and medullary
      vessels: a trio linked by hypoxia.

PMID- 25385851
TI  - Myocardial ischemia and reperfusion leads to transient CD8 immune deficiency and
      accelerated immunosenescence in CMV-seropositive patients.
AB  - RATIONALE: There is mounting evidence of a higher incidence of coronary heart
      disease in cytomegalovirus-seropositive individuals. OBJECTIVE: The aim of this
      study was to investigate whether acute myocardial infarction triggers an
      inflammatory T-cell response that might lead to accelerated immunosenescence in
      cytomegalovirus-seropositive patients. METHODS AND RESULTS: Thirty-four patients
      with acute myocardial infarction undergoing primary percutaneous coronary
      intervention were longitudinally studied within 3 months after reperfusion
      (Cohort A). In addition, 54 patients with acute myocardial infarction and chronic
      myocardial infarction were analyzed in a cross-sectional study (Cohort B).
      Cytomegalovirus-seropositive patients demonstrated a greater fall in the
      concentration of terminally differentiated CD8 effector memory T cells (TEMRA) in
      peripheral blood during the first 30 minutes of reperfusion compared with
      cytomegalovirus-seronegative patients (-192 versus -63 cells/MUL; P=0.008),
      correlating with the expression of programmed cell death-1 before primary
      percutaneous coronary intervention (r=0.8; P=0.0002). A significant proportion of
      TEMRA cells remained depleted for >=3 months in cytomegalovirus-seropositive
      patients. Using high-throughput 13-parameter flow cytometry and human leukocyte
      antigen class I cytomegalovirus-specific dextramers, we confirmed an acute and
      persistent depletion of terminally differentiated TEMRA and cytomegalovirus
      specific CD8(+) cells in cytomegalovirus-seropositive patients. Long-term
      reconstitution of the TEMRA pool in chronic cytomegalovirus-seropositive
      postmyocardial infarction patients was associated with signs of terminal
      differentiation including an increase in killer cell lectin-like receptor
      subfamily G member 1 and shorter telomere length in CD8(+) T cells (2225 versus
      3397 bp; P<0.001). CONCLUSIONS: Myocardial ischemia and reperfusion in
      cytomegalovirus-seropositive patients undergoing primary percutaneous coronary
      intervention leads to acute loss of antigen-specific, terminally differentiated
      CD8 T cells, possibly through programmed cell death-1-dependent programmed cell
      death. Our results suggest that acute myocardial infarction and reperfusion
      accelerate immunosenescence in cytomegalovirus-seropositive patients.

PMID- 25385853
TI  - Is the 'Act FAST' stroke campaign lobeist? The implications of including symptoms
      of occipital lobe and eye stroke in public education campaigns.

PMID- 25385854
TI  - Collateral benefit: the comeback of MOG antibodies as a biomarker in neurological
      practice.

PMID- 25385852
TI  - Mitochondrial dysfunction and insulin resistance: an update.
AB  - Mitochondrial dysfunction has been implicated in the development of insulin
      resistance (IR); however, a large variety of association and intervention studies
      as well as genetic manipulations in rodents have reported contrasting results.
      Indeed, even 39 years after the first publication describing a relationship
      between IR and diminished mitochondrial function, it is still unclear whether a
      direct relationship exists, and more importantly if changes in mitochondrial
      capacity are a cause or consequence of IR. This review will take a journey
      through the past and summarise the debate about the occurrence of mitochondrial
      dysfunction and its possible role in causing decreased insulin action in obesity
      and type 2 diabetes. Evidence is presented from studies in various human
      populations, as well as rodents with genetic manipulations of pathways known to
      affect mitochondrial function and insulin action. Finally, we have discussed
      whether mitochondria are a potential target for the treatment of IR. 

PMID- 25385855
TI  - Use of mosquito preventive measures is associated with increased RBC CR1 levels
      in a malaria holoendemic area of western Kenya.
AB  - Malaria is responsible for close to 1 million deaths each year, mostly among
      African children. Red blood cells (RBCs) of children with severe malarial anemia
      show loss of complement regulatory proteins such as complement receptor 1 (CR1).
      We carried out this study to identify socio-economic, environmental, and
      biological factors associated with the loss of RBC CR1. A cross-sectional study
      was conducted in a malaria holoendemic area of western Kenya. Twelve
      socioeconomic, environmental, and biological factors were examined for a
      relationship with RBC CR1 level using bivariate linear regression followed by
      creation of a multivariate linear regression model. A significant positive
      relationship between RBC CR1 level and use of mosquito countermeasures was found.
      However, there was no evidence of a significant relationship between RBC CR1
      level and malaria infection or parasitemia level. Reducing mosquito exposure may
      aid in the prevention of severe malarial anemia by reducing the number of
      infections and thus preserving RBC CR1. 

PMID- 25385856
TI  - Reactivity in rapidly collected hygiene and toilet spot check measurements: a
      cautionary note for longitudinal studies.
AB  - Discreet collection of spot check observations to measure household hygiene
      conditions is a common measurement technique in epidemiologic studies of hygiene
      in low-income countries. The objective of this study was to determine whether the
      collection of spot check observations in longitudinal studies could itself induce
      reactivity (i.e., change participant behavior). We analyzed data from a 12-month
      prospective cohort study in rural Tamil Nadu, India that was conducted in the
      absence of any hygiene or toilet promotion activities. Our data included hygiene
      and toilet spot checks from 10,427 household visits. We found substantial
      evidence of participant reactivity to spot check observations of hygiene
      practices that were easy to modify on short notice. For example, soap observed at
      the household's primary handwashing location increased from 49% at enrollment to
      81% by the fourth visit and remained at or above 77% for the remainder of the
      study. 

PMID- 25385857
TI  - Cysticercosis-related hospitalizations in the United States, 1998-2011.
AB  - Cysticercosis has become increasingly recognized as an important infection in the
      United States in recent decades. Despite its potential impact, there is a lack of
      comprehensive information on the nationwide burden of disease. To better define
      the burden of cysticercosis in the United States, we analyzed in-patient records
      using the Nationwide Inpatient Sample for 1998-2011 to estimate cysticercosis
      related hospitalizations and patient/institutional characteristics. There were an
      estimated 33,060 (95% confidence interval [95% CI] = 29,610.5-36,510.3)
      cysticercosis-related hospitalizations nationwide, representing a hospitalization
      rate of 8.03 per million population. The highest proportion of cases were male
      (54.8%), Hispanic (62.0%), aged 18-44 (58.8%), and occurred in the West (45.1%).
      An estimated 459 deaths occurred, representing an in-hospital case-fatality rate
      of 1.4%. These findings indicate the burden of cysticercosis-related
      hospitalizations in the United States is considerable and may be greater than
      currently appreciated. Cysticercosis should be a nationally reportable disease. 

PMID- 25385858
TI  - Two cases of false-positive dengue non-structural protein 1 (NS1) antigen in
      patients with hematological malignancies and a review of the literature on the
      use of NS1 for the detection of Dengue infection.
AB  - Early diagnosis of dengue has been made easier in recent years owing to the
      advancement in diagnostic technologies. The rapid non-structural protein 1 (NS1)
      test strip is widely used in many developed and developing regions at risk of
      dengue. Despite the relatively high specificity of this test, we recently
      encountered two cases of false-positive dengue NS1 antigen in patients with
      underlying hematological malignancies. We reviewed the literature for causes of
      false-positive dengue NS1. 

PMID- 25385859
TI  - Neuritis and gastrointestinal hemorrhage in scrub typhus patients.
AB  - A 78-year-old woman with scrub typhus exhibited gastric hemorrhage with multiple
      gastric ulcers. This is the first report to confirm pathologically the presence
      of not only vasculitis but also, neuritis. The results suggest the necessity of
      studies confirming neuritis as the cause of gastric ulcer and bleeding in scrub
      typhus. 

PMID- 25385860
TI  - Environmental surveillance for toxigenic Vibrio cholerae in surface waters of
      Haiti.
AB  - Epidemic cholera was reported in Haiti in 2010, with no information available on
      the occurrence or geographic distribution of toxigenic Vibrio cholerae in Haitian
      waters. In a series of field visits conducted in Haiti between 2011 and 2013,
      water and plankton samples were collected at 19 sites. Vibrio cholerae was
      detected using culture, polymerase chain reaction, and direct viable count
      methods (DFA-DVC). Cholera toxin genes were detected by polymerase chain reaction
      in broth enrichments of samples collected in all visits except March 2012.
      Toxigenic V. cholerae was isolated from river water in 2011 and 2013. Whole
      genome sequencing revealed that these isolates were a match to the outbreak
      strain. The DFA-DVC tests were positive for V. cholerae O1 in plankton samples
      collected from multiple sites. Results of this survey show that toxigenic V.
      cholerae could be recovered from surface waters in Haiti more than 2 years after
      the onset of the epidemic. 

PMID- 25385861
TI  - Performance of BinaxNOW G6PD deficiency point-of-care diagnostic in P. vivax
      infected subjects.
AB  - Accurate diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is
      required to avoid the risk of acute hemolysis associated with 8-aminoquinoline
      treatment. The performance of the BinaxNOW G6PD test compared with the
      quantitative spectrophotometric analysis of G6PD activity was assessed in 356
      Plasmodium vivax-infected subjects in Brazil, Peru, Thailand, and India. In the
      quantitative assay, the median G6PD activity was 8.81 U/g hemoglobin (range =
      0.05-20.19), with 11 (3%) subjects identified as deficient. Sensitivity of the
      BinaxNOW G6PD to detect deficient subjects was 54.5% (6 of 11), and specificity
      was 100% (345 of 345). Room temperatures inadvertently falling outside the range
      required to perform the rapid test (18-25 degrees C) together with subtlety of
      color change and insufficient training could partially explain the low
      sensitivity found. Ensuring safe use of 8-aminoquinolines depends on additional
      development of simple, highly sensitive G6PD deficiency diagnostic tests suitable
      for routine use in malaria-endemic areas. 

PMID- 25385862
TI  - Comparison of three molecular methods for the detection and speciation of five
      human Plasmodium species.
AB  - In this study, three molecular assays (real-time multiplex polymerase chain
      reaction [PCR], merozoite surface antigen gene [MSP]-multiplex PCR, and the
      PlasmoNex Multiplex PCR Kit) have been developed for diagnosis of Plasmodium
      species. In total, 52 microscopy-positive and 20 malaria-negative samples were
      used in this study. We found that real-time multiplex PCR was the most sensitive
      for detecting P. falciparum and P. knowlesi. The MSP-multiplex PCR assay and the
      PlasmoNex Multiplex PCR Kit were equally sensitive for diagnosing P. knowlesi
      infection, whereas the PlasmoNex Multiplex PCR Kit and real-time multiplex PCR
      showed similar sensitivity for detecting P. vivax. The three molecular assays
      displayed 100% specificity for detecting malaria samples. We observed no
      significant differences between MSP-multiplex PCR and the PlasmoNex multiplex PCR
      kit (McNemar's test: P = 0.1489). However, significant differences were observed
      comparing real-time multiplex PCR with the PlasmoNex Multiplex PCR Kit (McNemar's
      test: P = 0.0044) or real-time multiplex PCR with MSP-multiplex PCR (McNemar's
      test: P = 0.0012). 

PMID- 25385863
TI  - Fetal size in a rural melanesian population with minimal risk factors for growth
      restriction: an observational ultrasound study from Papua New Guinea.
AB  - We conducted a prospective longitudinal study of fetal size in rural Papua New
      Guinea (PNG) involving 439 ultrasound-dated singleton pregnancies with no obvious
      risk factors for growth restriction. Sonographically estimated fetal weights
      (EFWs; N = 788) and birth weights (N = 376) were included in a second-order
      polynomial regression model (optimal fit) to generate fetal weight centiles.
      Means for specific fetal biometric measurements were also estimated. Fetal weight
      centiles from a healthy PNG cohort were consistently lower than those derived
      from Caucasian and Congolese populations, which overestimated the proportion of
      fetuses measuring small for gestational age (SGA; < 10th centile). Tanzanian and
      global reference centiles (Caucasian weight reference adapted to our PNG cohort)
      were more similar to those observed in our cohort, but the global reference
      underestimated SGA. Individual biometric measurements did not differ
      significantly from other cohorts. In rural PNG, a locally derived nomogram may be
      most appropriate for detection of SGA fetuses. 

PMID- 25385864
TI  - Epidemiology of meningitis in an HIV-infected Ugandan cohort.
AB  - There is limited understanding of the epidemiology of meningitis among human
      immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We
      conducted a prospective cohort study of HIV-infected adults with suspected
      meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis.
      Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for
      bacterial, viral, fungal, and mycobacterial etiologies, including
      neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for
      bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2,
      cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Toxoplasma gondii; reverse
      transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF
      assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of
      meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among
      cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22%
      (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of
      71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new
      TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource
      limited settings remains needed, and implementation of cryptococcal diagnostics
      is critical. 

PMID- 25385865
TI  - Circulating serum markers and QRS scar score in Chagas cardiomyopathy.
AB  - Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30%
      will manifest Chagas cardiomyopathy (CC). Identification of reliable early
      indicators of CC risk would enable prioritization of treatment to those with the
      highest probability of future disease. Serum markers and electrocardiogram (EKG)
      changes were measured in 68 T. cruzi-infected individuals in various stages of
      cardiac disease and 17 individuals without T. cruzi infection or cardiac disease.
      T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray
      [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural
      changes). Ten serum markers were measured using enzyme-linked immunosorbent assay
      (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of
      transforming growth factor-beta1 (TGFbeta1), and TGFbeta2 were associated with
      stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue
      Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively
      with increasing CC severity. Elevated levels of several markers of cardiac damage
      and inflammation are seen in early CC and warrant additional evaluation in
      longitudinal studies. 

PMID- 25385866
TI  - Etiologies of illness among patients meeting integrated management of adolescent
      and adult illness district clinician manual criteria for severe infections in
      northern Tanzania: implications for empiric antimicrobial therapy.
AB  - We describe the laboratory-confirmed etiologies of illness among participants in
      a hospital-based febrile illness cohort study in northern Tanzania who
      retrospectively met Integrated Management of Adolescent and Adult Illness
      District Clinician Manual (IMAI) criteria for septic shock, severe respiratory
      distress without shock, and severe pneumonia, and compare these etiologies
      against commonly used antimicrobials, including IMAI recommendations for
      emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI
      first-line recommendations for severe pneumonia (ceftriaxone and a macrolide).
      Among 423 participants hospitalized with febrile illness, there were 25 septic
      shock, 37 severe respiratory distress without shock, and 109 severe pneumonia
      cases. Ceftriaxone had the highest potential utility of all antimicrobials
      assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe
      respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For
      each syndrome 17-27% of participants had etiologic diagnoses that would be non
      responsive to ceftriaxone, but responsive to other available antimicrobial
      regimens including amphotericin for cryptococcosis and histoplasmosis; anti
      tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline
      therapy for rickettsioses and Q fever. We conclude that although empiric
      ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in
      IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and
      tetracycline-responsive bacterial infections, were common. 

PMID- 25385867
TI  - Abundance, natural infection with trypanosomes, and food source of an endemic
      species of triatomine, Panstrongylus howardi (Neiva 1911), on the Ecuadorian
      Central Coast.
AB  - The elimination of domestic triatomines is the foundation of Chagas disease
      control. Regional initiatives are eliminating introduced triatomine species. In
      this scenario, endemic triatomines can occupy the ecological niches left open and
      become a threat to long-term Chagas disease control efforts. This study
      determined the abundance, colonization, and Trypanosoma cruzi infection rate of
      the endemic Panstrongylus howardi in 10 rural communities located in Ecuador's
      Manabi Province. In total, 518 individuals of P. howardi were collected.
      Infestation indices of 1.4% and 6.6% were found in the domestic and peridomestic
      environments, respectively. We determined a T. cruzi infection rate of 53.2% (N =
      47) in this species. P. howardi has a high capacity to adapt to different
      habitats, especially in the peridomicile. This implies a considerable risk of
      transmission because of the frequency of intradomicile invasion. Therefore, this
      species needs to be taken into account in Chagas control and surveillance efforts
      in the region. 

PMID- 25385868
TI  - Cervical cancer screening (Pap testing) behaviours and acceptability of human
      papillomavirus self-testing among lesbian and bisexual women aged 21-26 years in
      the USA.
AB  - OBJECTIVE: Lesbian and bisexual women are at risk for human papillomavirus (HPV)
      infection and cervical disease. We examined cervical cancer screening (Pap
      testing) behaviours among these women and their acceptability of HPV self-testing
      at home, a potential cervical cancer screening strategy. METHODS: We analysed
      data from a national sample of lesbian and bisexual women aged 21-26 years
      (n=418) who completed our online survey in Autumn 2013. Logistic regression
      identified correlates of (1) having had a Pap test in the last 3 years and (2)
      willingness to use an HPV self-test at home. RESULTS: About 70% of women had
      undergone a Pap test in the last 3 years. Pap testing was more common among women
      who had disclosed their sexual orientation to their health care provider [odds
      ratio (OR)=2.01, 95% confidence interval (CI) 1.02-3.95] and less common among
      women who self-identified as lesbian (OR=0.48, 95% CI 0.25-0.93). Just over half
      the women (51%) were willing to use an HPV self-test at home. Women were more
      willing to use an HPV self-test at home if they were older (OR=1.16, 95% CI 1.03
      1.30) or reported higher levels of worry about getting an HPV-related disease
      (OR=1.28, 95% CI 1.01-1.63). The most common concerns about HPV self-testing at
      home were using the test incorrectly (70%) and test accuracy (64%). CONCLUSIONS:
      Many young lesbian and bisexual women have not had a recent Pap test. HPV self
      testing at home may be a promising future strategy for reaching and screening
      these women. Findings highlight beliefs and concerns that could be addressed by
      self-test programmes.

PMID- 25385869
TI  - Emergence of infectious simian virus 40 whose AT tract in the replication
      origin/early promoter region is substituted by cellular or viral DNAs.
AB  - In simian virus 40 (SV40) and several other polyomaviruses, the TATA box of the
      early promoter is embedded in an AT tract that is also an essential part of the
      replication origin. We generated an 'AT trap', an SV40 genome lacking the AT
      tract and unable to grow in CV-1 monkey cells. Co-transfection of the AT trap
      with oligonucleotides containing AT tracts of human polyomaviruses, a poly(A : T)
      tract or variants of the SV40 WT sequence all restored infectious virus. In a
      transfection of the AT trap without a suitable oligonucleotide, an AT-rich
      segment was incorporated, stemming either from bovine (calf serum) or monkey
      (host cell) DNA. Similarly, when cells were grown with human serum, a human DNA
      segment was captured by SV40 to substitute for the missing AT stretch. We
      conclude that the virus is quite opportunistic in accepting heterologous
      substitutes, and that even low-abundance DNA from serum can be incorporated into
      the viral genome.

PMID- 25385870
TI  - Hyperglycemia has no effect on development of restenosis after percutaneous
      transluminal angioplasty (PTA) in a diabetic rabbit model.
AB  - It is well known that hyperglycemia is a trigger of atherosclerosis in patients
      with diabetes mellitus. However, the role of hyperglycemia in restenosis remains
      unclear. In this study, we investigated the effects of hyperglycemia on
      restenosis. Stenosis was evaluated in two sets of diabetic rabbit models: i)
      diabetic restenosis versus nondiabetic restenosis and ii) diabetic
      atherosclerosis versus nondiabetic atherosclerosis. Our results indicated that
      there was no difference in rates of stenosis between the diabetic and the
      nondiabetic groups in restenosis rabbit models. However, the incidence of
      stenosis was significantly higher in the diabetic atherosclerosis group compared
      with the nondiabetic atherosclerosis group. Similarly, the intima-media thickness
      and cell proliferation rate were significantly increased in the diabetic
      atherosclerosis group compared with the nondiabetic atherosclerosis group, but
      there was no difference between the diabetic restenosis and the nondiabetic
      restenosis groups. Our results indicate that hyperglycemia is an independent risk
      factor for atherosclerosis, but it has no evident effect on restenosis. These
      findings indicate that the processes of atherosclerosis and restenosis may
      involve different pathological mechanisms. 

PMID- 25385871
TI  - RGC32 deficiency protects against high-fat diet-induced obesity and insulin
      resistance in mice.
AB  - Obesity is an important independent risk factor for type 2 diabetes,
      cardiovascular diseases and many other chronic diseases. Adipose tissue
      inflammation is a critical link between obesity and insulin resistance and type 2
      diabetes and a contributor to disease susceptibility and progression. The
      objective of this study was to determine the role of response gene to complement
      32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32
      knockout (Rgc32(-/-) (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for
      12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1
      preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32(
      /-) mice fed with HFD exhibited a lean phenotype with reduced epididymal fat
      weight compared with WT controls. Blood biochemical analysis and insulin
      tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and
      insulin resistance. Although it had no effect on adipocyte differentiation, RGC32
      deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32(
      /-) induced browning of adipose tissues and increased energy expenditure. Our
      data indicated that RGC32 plays an important role in diet-induced obesity and
      insulin resistance, and thus it may serve as a potential novel drug target for
      developing therapeutics to treat obesity and metabolic disorders. 

PMID- 25385872
TI  - Effects of glucocorticoids on human brown adipocytes.
AB  - Clinical cases of glucocorticoid (GC) excess are characterized by increased fat
      mass and obesity through the accumulation of white adipocytes. The effects of GCs
      on growth and function of brown adipose tissue are unknown and may contribute to
      the negative energy balance observed clinically. This study aims to evaluate the
      effect of GCs on proliferation, differentiation, and metabolic function of brown
      adipocytes. Human brown adipocytes sourced from supraclavicular fat biopsies were
      grown in culture and differentiated to mature adipocytes. Human white adipocytes
      sourced from subcutaneous abdominal fat biopsies were cultured as controls.
      Effects of dexamethasone on growth, differentiation (UCP1, CIDEA, and PPARGC1A
      expression), and function (oxygen consumption rate (OCR)) of brown adipocytes
      were quantified. Dexamethasone (1 MUM) significantly stimulated the proliferation
      of brown preadipocytes and reduced that of white preadipocytes. During
      differentiation, dexamethasone (at 0.1, 1, and 10 MUM) stimulated the expression
      of UCP1, CIDEA, and PPARGC1A in a concentration-dependent manner and enhanced by
      fourfold to sixfold the OCR of brown adipocytes. Isoprenaline (100 nM)
      significantly increased (P<0.05) expression of UCP1 and OCR of brown adipocytes.
      These effects were significantly reduced (P<0.05) by dexamethasone. Thus, we show
      that dexamethasone stimulates the proliferation, differentiation, and function of
      human brown adipocytes but inhibits adrenergic stimulation of the functioning of
      brown adipocytes. We conclude that GCs exert complex effects on development and
      function of brown adipocytes. These findings provide strong evidence for an
      effect of GCs on the biology of human brown adipose tissue (BAT) and for the
      involvement of the BAT system in the metabolic manifestation of Cushing's
      syndrome. 

PMID- 25385873
TI  - E-cigarette Use Among High School and Middle School Adolescents in Connecticut.
AB  - INTRODUCTION: There is limited evidence on electronic cigarette (e-cigarette) use
      among U.S. adolescents. METHODS: Cross-sectional, anonymous surveys conducted in
      4 high schools (HS; n = 3,614) and 2 middle schools (MS; n = 1,166) in
      Connecticut in November 2013 examined e-cigarette awareness, use patterns,
      susceptibility to future use, preferences, product components used (battery type,
      nicotine content, flavors), and sources of marketing and access. RESULTS: High
      rates of awareness (MS: 84.3%; HS: 92.0%) and of lifetime (3.5% MS, 25.2 % HS)
      and current (1.5% MS, 12% HS) use of e-cigarettes was observed. Among those who
      had not tried e-cigarettes, 26.4% of MS and 31.7% of HS students reported being
      susceptible to future use. Males (OR = 1.70, p < .01), older students (OR = 1.39,
      p < .05), Caucasians (OR = 2.01, p < .001), ever cigarette smokers (OR = 13.04, p
      < .001), and current cigarette smokers (OR = 65.11, p < .001) were more likely to
      be lifetime e-cigarette users and to report greater future susceptibility (males:
      OR = 1.30; Caucasians: OR = 1.14; ever cigarette smokers; OR = 3.85; current
      cigarette smokers; OR = 9.81; ps < .01-.001). Among MS students who were lifetime
      e-cigarette users, 51.2% reported that e-cigarette was the first tobacco product
      they had tried. E-cigarettes that were rechargeable and had sweet flavors were
      most popular. Smokers preferred e-cigarettes to cigarettes. Current cigarette
      smokers were more likely to initiate with nicotine-containing e-cigarettes, and
      ever and never cigarette smokers to initiate with e-cigarettes without nicotine.
      Primary sources for e-cigarette advertisements were televisions and gas stations
      and, for acquiring e-cigarettes, were peers. CONCLUSIONS: Longitudinal monitoring
      of e-cigarette use among adolescents and establishment of policies to limit
      access are imperatively needed.

PMID- 25385874
TI  - Cessation among state quitline participants with a mental health condition.
AB  - INTRODUCTION: Telephone quitlines are an effective treatment option for tobacco
      cessation in the general population. Many participants who use quitline services
      have mental health conditions (MHC), yet few published studies have examined the
      use of quitline services in this population. This study examined the prevalence
      of MHC among state quitline participants and compared cessation outcomes among
      those with and without MHC. METHODS: Demographic and tobacco use data were
      collected at enrollment and 7 months post-enrollment using standardized
      assessments for 10,720 eligible participants who enrolled in a state quitline
      between September, 2010 and August, 2012. RESULTS: The prevalence of self
      reported MHC was 19.8% (2,086/10,720 callers). The intent to treat quit rate for
      participants with a MHC was 16.4% compared to 21.5% for those without a MHC (p <
      .001), and the responder quit rate was 36.9% for those with a MHC compared to
      44.4% for those without (p < .001). The adjusted odds ratio describing the
      association of MHC status and tobacco cessation was identical for both the intent
      to-treat and responder populations, and indicated that participants with MHC were
      23% less likely to quit (p < .05). CONCLUSIONS: This study identified that
      participants with MHC accessed a state quitline, but were less likely to quit.
      The finding was independent of other factors influencing tobacco cessation, such
      as gender, race, and education. These findings indicate that although quitline
      services are an option for tobacco cessation among persons with MHC, further
      research is needed to determine why cessation rates are lower.

PMID- 25385875
TI  - Tobacco Use, Quitting Behavior, and Health Characteristics Among Current
      Electronic Cigarette Users in a National Tri-Ethnic Adult Stable Smoker Sample.
AB  - INTRODUCTION: The present study characterizes the tobacco use, quitting
      behaviors, and health characteristics of cigarette smokers who did not change
      their smoking pattern over the past 6 months and have used electronic cigarettes
      (ECs) in the past 30 days. This is an important subpopulation to characterize if
      EC dual use with cigarettes continues to grow. METHODS: Participants (N = 2,376)
      from a research survey panel completed an online cross-sectional survey between
      June and August 2012. Sampling was stratified to recruit equal numbers of
      cigarette smoking participants by race/ethnicity (Black, Hispanic, and Caucasian)
      and smoking frequency (nondaily and daily). All displayed a stable rate of
      smoking for the past 6 months and were not currently in treatment. Bivariate and
      multivariate analyses were used to examine correlates of current EC use (any use
      within the past 30 days). RESULTS: Current EC use was reported by 9.2% (n = 219)
      of the total sample. Of current EC users, 44% reported having used ECs as a quit
      method. Bivariate and multivariate analyses showed that current EC use was
      significantly associated with greater nicotine dependence, concurrent poly
      tobacco use, more past-year quit attempts, past use of multiple cessation
      methods, and more depressive symptoms. No demographic variables were
      significantly associated with current EC use. CONCLUSIONS: This study suggests
      that stable smokers who currently use ECs possess characteristics that are
      associated with difficulty in achieving smoking cessation. These characteristics
      should be considered when examining the effectiveness of ECs on cessation and in
      designing future cessation trials using ECs.

PMID- 25385876
TI  - Prevalence and Correlates of Social Smoking in Young Adults: Comparisons of
      Behavioral and Self-Identified Definitions.
AB  - INTRODUCTION: Social smoking is an increasingly common pattern among emerging
      adults. Although distinct patterns have emerged between social smokers and non
      social smokers, there is discrepancy about how to define the construct, with
      inconsistencies between self-identified social smoking and behavioral social
      smoking. We report prevalence and correlates of young adult smokers who self
      identify and behave as social smokers (SELF + BEH), self-identified non
      behavioral social smokers (SELF-ONLY), and non-social smokers (NON-SOCIAL).
      METHODS: Young adults age 18-25 years who have smoked at least 1 cigarette in the
      past 30 days (N = 1,811) were recruited through Facebook for a national
      anonymous, online survey of tobacco and other substance use. Three social smoking
      items were used to categorize respondents into 1 of 3 smoking groups. Groups were
      examined for prevalence and differences on demographics, substance use,
      motivation to quit smoking and thoughts about tobacco abstinence. RESULTS: SELF
      ONLY (46%) was the largest group, followed by SELF + BEH (27%) and NON-SOCIAL
      (27%). SELF + BEH smoke less frequently, smoke fewer cigarettes per day, are less
      addicted to cigarettes, have a higher desire to quit, and perceive a lower
      quitting difficulty compared with SELF-ONLY. SELF + BEH and SELF-ONLY were more
      likely to be male, be marijuana users, and be addicted to marijuana than NON
      SOCIAL. SELF + BEH exhibited a lower frequency of smoking, less cigarettes per
      day, were less addicted, and had more days co-using alcohol and cigarettes than
      NON-SOCIAL. CONCLUSION: Identifying social smokers based on self-identification
      in addition to behavioral components appears to be important for designing
      smoking cessation interventions for emerging adults.

PMID- 25385877
TI  - Work and Non-Work Physical Activity Predict Real-Time Smoking Level and Urges in
      Young Adults.
AB  - INTRODUCTION: Physical activity (PA) and smoking are inversely related. However,
      evidence suggests that some types of PA, namely work-related PA, may show an
      opposite effect. Despite growing knowledge, there remains a paucity of studies
      examining the context of these behaviors in naturalistic settings or in young
      adults, a high-risk group for escalation. METHODS: Participants were 188 young
      adults (mean age = 21.32; 53.2% female; 91% current smokers) who participated in
      an electronic diary week to assess daily smoking and urges and a PA recall to
      examine daily PA. PA was coded into non-work-related and work-related activity to
      examine differential effects. We considered both participants' weekly average PA
      and their daily deviations from their average. RESULTS: Mixed-effects regression
      models revealed that higher weekly average non-work PA was associated with lower
      smoking level and urges. Daily deviations in non-work PA did not predict urges;
      however, increased daily non-work PA relative to participants' weekly average was
      associated with lower smoking for females but higher levels for males. Regarding
      work PA, only higher weekly average work PA was associated with higher smoking
      level for both genders; work PA did not predict urges. CONCLUSIONS: Results
      extend previous literature by documenting differential associations between non
      work and work PA and young adult smoking and suggest that young adults engaged in
      work PA should be considered a high-risk group for escalation. Findings provide
      theoretical and clinical implications for the use of PA in intervention and
      highlight the necessity of considering PA as a multidimensional construct when
      examining its links to health behavior.

PMID- 25385878
TI  - Evaluation of a novel nicotine inhaler device: part 1--arterial and venous
      pharmacokinetics.
AB  - INTRODUCTION: In the United Kingdom, licensed nicotine-containing products can be
      recommended to reduce the harm associated with smoking. Many smokers find
      currently available nicotine replacement products unsatisfactory. The arterial
      and venous pharmacokinetics (PK) of nicotine delivered via a novel inhaler device
      were determined. METHODS: Results are reported for Parts A (N = 18) and C (N =
      18) of a 4-part (A-D) Phase I study. Participants (18-55 years, >= 10
      cigarettes/day, smoking within 1 hr of waking, expired carbon monoxide >10 ppm on
      screening) orally inhaled 2 single doses of nicotine (2 of 3 dose levels [0.22,
      0.45, and 0.67 mg]) (Part A) and repeated hourly doses of 0.67 mg nicotine for 12
      hr (Part C), via the novel device. Arterial and venous PK and tolerability were
      assessed. RESULTS: In Part A, mean arterial plasma nicotine concentrations at 2
      min after the start of inhalation were 1.10, 2.06, and 2.59 ng/mL for the 0.22,
      0.45, and 0.67 mg doses, respectively. Mean maximum arterial plasma nicotine
      concentrations (C(max)) were 2.11, 3.73, and 4.38 ng/mL and mean times to C(max)
      were 10.2, 7.3, and 6.5 min after the start of inhalation for the 0.22, 0.45, and
      0.67 mg doses, respectively. In Part C, the mean pre- and postdose venous plasma
      nicotine concentration increased steadily and fluctuated in the range 8-10 mg/mL
      after 9 hr. The novel device was well tolerated; most adverse events were mild.
      CONCLUSION: The novel inhaler device delivers nicotine rapidly into the systemic
      circulation and offers a viable alternative to cigarettes for those finding it
      difficult to quit the behavioral and sensorial aspects of smoking.

PMID- 25385879
TI  - Obesity-related hypertension: possible pathophysiological mechanisms.
AB  - Hypertension is one of the major risk factors of cardiovascular diseases, but
      despite a century of clinical and basic research, the discrete etiology of this
      disease is still not fully understood. The same is true for obesity, which is
      recognized as a major global epidemic health problem nowadays. Obesity is
      associated with an increasing prevalence of the metabolic syndrome, a cluster of
      risk factors including hypertension, abdominal obesity, dyslipidemia, and
      hyperglycemia. Epidemiological studies have shown that excess weight gain
      predicts future development of hypertension, and the relationship between BMI and
      blood pressure (BP) appears to be almost linear in different populations. There
      is no doubt that obesity-related hypertension is a multifactorial and polygenic
      trait, and multiple potential pathogenetic mechanisms probably contribute to the
      development of higher BP in obese humans. These include hyperinsulinemia,
      activation of the renin-angiotensin-aldosterone system, sympathetic nervous
      system stimulation, abnormal levels of certain adipokines such as leptin, or
      cytokines acting at the vascular endothelial level. Moreover, some genetic and
      epigenetic mechanisms are also in play. Although the full manifestation of both
      hypertension and obesity occurs predominantly in adulthood, their roots can be
      traced back to early ontogeny. The detailed knowledge of alterations occurring in
      the organism of experimental animals during particular critical periods
      (developmental windows) could help to solve this phenomenon in humans and might
      facilitate the age-specific prevention of human obesity-related hypertension. In
      addition, better understanding of particular pathophysiological mechanisms might
      be useful in so-called personalized medicine. 

PMID- 25385881
TI  - Track a: biomaterials and biocompatibility.

PMID- 25385882
TI  - Track o: prevention and rehabilitation engineering.

PMID- 25385883
TI  - Track P: Active and intelligent implants.

PMID- 25385880
TI  - The risks of acute exposure to black carbon in Southern Europe: results from the
      MED-PARTICLES project.
AB  - OBJECTIVES: While several studies have reported associations of daily exposures
      to PM2.5 (particles less than 2.5 um) with mortality, few studies have examined
      the impact of its constituents such as black carbon (BC), which is also a
      significant contributor to global climate change. METHODS: We assessed the
      association between daily concentrations of BC and total, cardiovascular and
      respiratory mortality in two southern Mediterranean cities. Daily averages of BC
      were collected for 2 years in Barcelona, Spain and Athens, Greece. We used case
      crossover analysis and examined single and cumulative lags up to 3 days. RESULTS:
      We observed associations between BC and all mortality measures. For a 3-day
      moving average, cardiovascular mortality increased by 4.5% (95% CI 0.7 to 8.5)
      and 2.0% (95% CI 0 to 4.0) for an interquartile change in BC in Athens and
      Barcelona, respectively. Considerably higher effects for respiratory mortality
      and for those above age 65 were observed. In addition, BC exhibited much greater
      toxicity per microgram than generic PM2.5. CONCLUSIONS: Our findings suggest that
      BC, derived in western industrialised nations primarily from diesel engines and
      biomass burning, poses a significant burden to public health, particularly in
      European cities with high-traffic density.

PMID- 25385884
TI  - Track B: biosensors and bioanalytics, micro-nano technologies.

PMID- 25385885
TI  - Track q: training and further education.

PMID- 25385886
TI  - Track R: usability and quality control.

PMID- 25385887
TI  - Track C: biosignal processing.

PMID- 25385888
TI  - Track d: cellular, tissue and bioengineering.

PMID- 25385889
TI  - Track e: clinical and ambulatory monitoring.

PMID- 25385890
TI  - Track f: devices and systems for surgical interventions.

PMID- 25385891
TI  - Track G: Home Health care and AAL.

PMID- 25385892
TI  - Track H: Image guided interventions.

PMID- 25385893
TI  - Track I: imaging and image processing.

PMID- 25385894
TI  - Track j: magnetic methods in medicine.

PMID- 25385895
TI  - Track k: medical information systems.

PMID- 25385896
TI  - Track L: miscellaneous.

PMID- 25385897
TI  - Track m: modelling and simulation.

PMID- 25385898
TI  - Eye coding mechanisms in early human face event-related potentials.
AB  - In humans, the N170 event-related potential (ERP) is an integrated measure of
      cortical activity that varies in amplitude and latency across trials. Researchers
      often conjecture that N170 variations reflect cortical mechanisms of stimulus
      coding for recognition. Here, to settle the conjecture and understand cortical
      information processing mechanisms, we unraveled the coding function of N170
      latency and amplitude variations in possibly the simplest socially important
      natural visual task: face detection. On each experimental trial, 16 observers saw
      face and noise pictures sparsely sampled with small Gaussian apertures. Reverse
      correlation methods coupled with information theory revealed that the presence of
      the eye specifically covaries with behavioral and neural measurements: the left
      eye strongly modulates reaction times and lateral electrodes represent mainly the
      presence of the contralateral eye during the rising part of the N170, with
      maximum sensitivity before the N170 peak. Furthermore, single-trial N170
      latencies code more about the presence of the contralateral eye than N170
      amplitudes and early latencies are associated with faster reaction times. The
      absence of these effects in control images that did not contain a face refutes
      alternative accounts based on retinal biases or allocation of attention to the
      eye location on the face. We conclude that the rising part of the N170, roughly
      120-170 ms post-stimulus, is a critical time-window in human face processing
      mechanisms, reflecting predominantly, in a face detection task, the encoding of a
      single feature: the contralateral eye. 

PMID- 25385899
TI  - Comparative evaluation of the fracture resistances of endodontically treated
      teeth filled using five different root canal filling systems.
AB  - AIM: The aim of this study was to compare the fracture resistances of teeth
      filled using different root canal sealers and rials. MATERIALS AND METHODS: One
      hundred and twenty single rooted mandibular human incisor teeth with single
      canals were divided into 5 experimental groups of 20 teeth with 2 control groups
      of 10 teeth each. After root canal shaping using K3 rotary instruments, root
      canals were filled as follows: Group 1: (-) control, Group 2: (+) control, Group
      3: Gutta-percha/AH Plus, Group 4: Thermafil/AH Plus, Group 5: Resilon/Epiphany
      self-etch (Epiphany SE), Group 6: Gutta-percha/Epiphany SE ve Group 7: EndoREZ
      sealer/EndoREZ cone. After the root canal sealers set, the apical 4 mm. portions
      of the specimens were embedded in cold curing acrylic and a fracture resistance
      test was applied in a universal testing machine. The load at which fracture
      occurred was recorded for each group and statistically analyzed using one-way
      ANOVA and Tukey's honestly significant difference tests. RESULTS:
      Resilon/Epiphany SE ve EndoREZ sealer/EndoREZ cone groups had lower fracture
      resistances compared with the negative control group consisted of teeth without
      root canal shaping (P < 0.05). Gutta-percha/AH Plus, Thermafil/AH Plus and Gutta
      percha/Epiphany SE groups showed similar fracture resistances (P > 0.05). The
      fracture resistance of the instrumented, but unfilled positive control group was
      significantly lower compared with (-) control, Gutta-percha/AH Plus, Thermafil/AH
      Plus (P < 0.01) and Gutta-percha/Epiphany SE (P < 0.05) groups. There were no
      significant differences between the fracture resistances of the Resilon/Epiphany
      SE and EndoREZ sealer/EndoREZ cone and positive control groups (P > 0.05).
      CONCLUSIONS: Root canal shaping procedures decrease the fracture resistance of
      teeth, and lateral condensation performed with AH Plus sealer and Gutta-percha
      and the Thermafil technique were found to be more successful.

PMID- 25385900
TI  - Pattern of mandibular third molar impaction: A cross-sectional study in northeast
      of Iran.
AB  - OBJECTIVES: Impacted teeth, if left untreated, have a potential to induce various
      complications. The aim of the current study was to determine the prevalence and
      pattern of impacted mandibular third molar in the Iranian population. STUDY
      DESIGN: This cross-sectional study was performed in patients who were referred to
      the Department of Oral Radiology between July 2009 and October 2010 to obtain an
      orthopantomogram (OPG). Data were collected regarding age and gender, prevalence
      of impacted mandibular third molars, angulation of impacted teeth (Winter's
      classification), level of impaction (Pell and Gregory classification), and
      relationship of the mandibular third molar with the ramus (Pell and Gregory
      classification). The collected data were analyzed using SPSS software version
      11.0 with a confidence interval of 95%. RESULTS: Among the 1433 patients included
      in the study, 489 (34.12%) patients were male and 944 (65.88%) were female. Of
      the total OPGs performed, 871 (60.78%) OPGs demonstrated at least one impacted
      mandibular third molar. In addition, of the 2866 mandibular third molars
      investigated, 1397 (48.74%) were found to be impacted. A significant association
      was observed between gender and the number of impacted teeth or the presence of
      impaction of any mandibular tooth (or teeth) (P < 0.05). The most common type of
      tooth angulation was mesioangular (48.67%). In addition, the most prevalent type
      of impaction level and ramus relationship was level B (63.85%) and Class II
      (48.46%), respectively. There were no significant differences between the two
      sides of the mandible for the prevalence of impacted third molar (P > 0.05).
      CONCLUSION: The pattern of mandibular third molars in the Northeast region of
      Iran revealed a high prevalence of impaction, which was mostly mesioangular,
      level B, and Class II with a gender predilection for females.

PMID- 25385901
TI  - Mistreatment among undergraduate medical trainees: A case study of a Nigerian
      medical school.
AB  - BACKGROUND: Several international studies have shown that abuse or mistreatment
      is a regular phenomenon faced by medical students. However, there is limited
      information on medical student abuse/mistreatment in Nigeria. The study was
      therefore conducted to assess the prevalence and patterns of mistreatment
      experienced by Medical Students in the University of Calabar. MATERIALS AND
      METHODS: A descriptive cross-sectional study was conducted among 451
      undergraduate medical trainees in the University of Calabar. Systematic sampling
      was used in recruiting participants into the study. A self-administered
      questionnaire was then employed to obtain information on patterns of mistreatment
      experienced by medical undergraduates. Data were analyzed using Statistical
      Package for Social Scientists version 19 and level of significance set at <0.05.
      RESULTS: More than a third (35.5%) of all respondents interviewed had experienced
      one or more forms of mistreatment during their training, with 38.5% of them
      experiencing it weekly. The most common form of mistreatment experienced was
      verbal abuse (52.5%), and the main perpetrators of these incidents were medical
      consultants, (18.6%) other cadre of doctors (17.3%) and lecturers (14.4%). Being
      in the clinical level of study and aged above 25 years were significantly
      associated with experiencing mistreatment in this study (P < 0.05). However, only
      8.8% reported these incidents. CONCLUSION: With more than a third of
      undergraduate medical trainees experiencing mistreatment, development of
      appropriate strategies for the prevention and reduction of these incidents are
      strongly recommended.

PMID- 25385902
TI  - Relationship between obesity and oral diseases.
AB  - OBJECTIVE: The aim of this study was to determine the relationship between
      obesity and periodontal status and dental caries experience of a group of
      Nigerian dental patients. MATERIALS AND METHODS: Participants were selected from
      patients attending dental outpatient clinics of the University of Benin Teaching
      Hospital, Benin City, Nigeria. Their weight and height were measured and body
      mass index (BMI) estimated in kg/m 2 , gingival health assessed using bleeding on
      probing index, oral hygiene estimated using the simplified oral hygiene index
      (OHI-S), periodontal health estimated using the basic periodontal examination
      (BPE) and caries experience was estimated with the decayed, missing, and filled
      teeth (DMFT) index. RESULTS: A few participants (3.8%) were underweight, 52.6%
      fell within the normal BMI range, 28.2% preobese, 12.2% obese class I and 3.2%
      obese class II. The mean OHI-S score was 2.16 +/- 1.13 among the overweight
      participants and 2.05 +/- 1.13 among those who are not (P = 0.543). The mean DMFT
      score was 3.03 +/- 4.25 among the overweight participants and 2.32 +/- 3.01 among
      those who are not (P = 0.223). Sixty-five percent of participants with BPE score
      of 0, considered to signify periodontal health, had normal BMI while all the
      participants with the worst BPE score recorded belong to the obese 1 group (P =
      0.070). The binary logistic regression revealed that the likely predictor of
      gingival bleeding in the study is BMI between 35.0 and 39.9 (obese class 2) (P =
      0.046, odds ratio = 0.07, 95% confidence interval = 0.01-0.96). CONCLUSION: It
      can be concluded from this study that there is no statistically significant
      relationship between obesity and periodontal status and dental caries experience
      in the studied group of dental patients. Increased BMI may however be a predictor
      of gingival bleeding.

PMID- 25385903
TI  - Knowledge, attitude, and infection control practices of two tertiary hospitals in
      Port-Harcourt, Nigeria.
AB  - BACKGROUND: Surgical site infections (SSIs) are a significant cause of morbidity,
      emotional stress and financial cost to the affected patients and health care
      institutions, and infection control policy has been shown to reduce the burden of
      SSI in several health care institutions. This study assessed the effects of the
      implementation of the policy in a tertiary hospital in Port Harcourt, Nigeria.
      MATERIALS AND METHODS: A cross-sectional, comparative study design was used for
      the study, with data collected using a structured questionnaire and guided
      observation of doctors and nurses involved in the management of patients that had
      caesarean sections in two comparable tertiary hospitals in Port Harcourt-the
      University of Port Harcourt Teaching Hospital (UPTH) and the Braithwaite Memorial
      Specialist Hospital (BMSH). RESULTS: There were no statistically significant
      differences in the designations and length of practice of the respondents in both
      hospitals (P = 0.77). However, 63.64% of the respondents in UPTH were aware of
      the infection control committee, compared with none in BMSH. The appropriate
      timing for the administration of prophylactic antibiotics, and for the removal of
      the hair at the incision site were observed by 57.58% and 69.69% respectively of
      the respondents in UPTH, compared with 22.86% (P = 0.00) and 0.00% (P = 0.02) in
      BMSH. The reasons given by the respondents in UPTH for nonadherence to the
      infection control policy include poor supervision (39.39%) and lack of in-service
      training (21.21%), while the respondents in BMSH gave reasons that include
      inadequate supply of consumables (34.29%) and absence of a hospital's policy on
      infection control (22.88%). CONCLUSION: The implementation of the infection
      control policy resulted in some improvements in certain infection control
      practices.

PMID- 25385904
TI  - Comparison of anaesthetic cost in open and laparoscopic appendectomy.
AB  - CONTEXT: Appendectomy is generally conducted as open or by laparoscopic surgical
      techniques under general anesthesia. AIMS: This study aims to compare the
      anesthetic costs of the patients, who underwent open or laparoscopic appendectomy
      under general anesthesia. SETTINGS AND DESIGN: The design is retrospective and
      records of 379 patients who underwent open or laparoscopic appendectomy under
      general anesthesia, falling under the category of I-III risk group according to
      the American Society of Anesthesiologists (ASA) classification between the years
      2011 and 2013, and aged 18-77. SUBJECTS AND METHODS: Open (Group I) or
      laparoscopic (Group II) appendectomy operation under general anesthesia were
      evaluated retrospectively by utilizing hospital automation and anesthesia
      observation records. This study evaluated the anesthesia time of the patients and
      total costs (Turkish Lira ?, US dollar $) of anesthetic agents used (induction,
      maintenance), necessary medical materials (connecting line, endotracheal tube,
      airway, humidifier, branule, aspiration probe), and intravenously administered
      fluids were evaluated. STATISTICAL ANALYSIS USED: We used Statistical Package for
      the Social Sciences software (SPSS version 17.0) for statistical analysis.
      RESULTS: Of the patients, 237 were males (62.53%) and 142 were females (37.47%).
      Anesthesia time limits were established as 70.30 +/- 30.23 minute in Group I and
      74.92 +/- 31.83 minute in Group II. Mean anesthesia administration cost per
      patient was found to be 78.79 +/- 30.01? (39.16 +/- 14.15$) in Group I and 83.09
      +/- 26.85? (41.29 +/- 13.34$) in Group II (P > 0.05). A correlation was observed
      between cost and operation times (P = 0.002, r = 0.158). CONCLUSIONS: Although a
      statistical difference was not established in this study in terms of time and
      costs in appendectomy operations conducted as open and laparoscopically, changes
      may occur in time in market conditions of drugs, patent rights, legal
      regulations, and prices. Therefore, we believe that it would be beneficial to
      update and revise cost analyses from time to time.

PMID- 25385905
TI  - Self-perceived seizure precipitants among patients with epilepsy in Middle-belt
      of Nigeria.
AB  - AIM: Patient's perception of seizure precipitant is crucial in epilepsy
      management, but it is often overlooked by physicians. This may be due to neglect
      and underestimation of its importance. This study looked at frequency and nature
      of self-perceived seizure precipitants among patients with epilepsy. MATERIALS
      AND METHODS: A close-ended questionnaire-based study. Patients with active
      epilepsy (>=2 attacks/year) were recruited from the neurology clinic of the
      University of Ilorin Teaching Hospital (UITH), Ilorin. RESULT: A total of 89
      patients participated in the study and of these 41 (46.1%) were males. Their
      median age was 30 (21-52) years and median age at seizure onset was 22 (15-46)
      years. The median seizure duration was five (2-14) years. More patients (46.1%)
      had less than secondary school education and 12 (13.5) were uneducated.
      Generalized epilepsy was the predominant (68.6%) seizure type. A total of 33
      (37.1%) subjects had >=4 attacks/year, 29 (32.6%) had 5-12 attacks/year, and 27
      (30.3%) >12 attacks/year. A total of 16 (18%) subjects did not mention any
      seizure precipitant, whereas 73 (82.2%) reported at least one specific seizure
      precipitant; of these, 62 (85%) patients reported >=2 precipitants. Stress (41%),
      inadequate sleep (27%), and head trauma (26%) were the three leading seizure
      precipitants mentioned. Subject's age, sex, level of seizure control, and place
      of abode did not influence reported seizure precipitants. However, the more
      educated (>12 years education) patients significantly reported stress as seizure
      precipitant (P < 0.05). Most (80%) patients rightly indicated that antiepileptic
      drug was the best treatment for their seizure control. CONCLUSION: The result of
      this study showed that the leading perceived seizure precipitants among epilepsy
      patients attending the neurology clinic of UITH were stress, inadequate sleep,
      head trauma, and demonic attacks and spells.

PMID- 25385906
TI  - In vitro comparison of four different electronic apex locators to determine the
      major foramen using the clearing technique.
AB  - OBJECTIVES: The aim of this study was to evaluate the accuracy of four electronic
      apex locators (EALs) (DentaPort ZX, Raypex 5, Endo Master and VDW Gold) in
      detecting the major foramen using the clearing technique. MATERIALS AND METHODS:
      Forty-eight extracted single-rooted extracted teeth with mature apices were used
      for the study and divided into four groups of 12 teeth each. All teeth were
      embedded in an alginate model. Electronic measurements were taken using a size 15
      K-file attached to the holder. Then, the teeth were cleared and photographed
      under a stereomicroscope with a digital camera. The distance between the tip of
      the file and the major foramen was measured by using an image analysis software
      program. Positive and negative values were recorded when the file tip was beyond
      or short of the major foramen and zero value when the file tip and the major
      foramen coincided. Statistical analysis was performed using the Kruskal-Wallis
      and Chi-square tests at a significance level of 0.05. RESULTS: Mean distance from
      the file tip to the major foramen were 0.302 +/- 0.202, 0.065 +/- 0.293, 0.117 +/
      0.475, and 0.258 +/- 0.160 mm in the DentaPort ZX, Raype 5, Endo Master, and VDW
      Gold groups, respectively. There were no statistically significant differences
      among the devices (P > 0.05) . CONCLUSION: Under the experimental conditions, all
      EALs showed an acceptable determination of the major foramen.

PMID- 25385907
TI  - Medical causes of death in a teaching hospital in South-Eastern Nigeria: A 16
      year review.
AB  - BACKGROUND: Most developing regions of the world are undergoing gradual
      epidemiological transition resulting in high burden of both communicable and
      noncommunicable diseases. This affects the pattern of death in this region.
      OBJECTIVE: The objective of this study is to determine the causes of death in the
      medical wards of the University of Nigeria Teaching Hospital, Ituku/Ozalla,
      Enugu, South-East Nigeria from 1995 to 2010. MATERIALS AND METHODS: Data were
      collected retrospectively from January 1995 to December 2010. STATISTICAL
      ANALYSIS USED: Statistical Package for Social Sciences (SPSS Inc. Chicago, IL,
      USA) version 17.0 was used. Simple descriptive statistics were done. Student's t
      test was used to compare means of continuous variables, while Chi-square test was
      used to test significance of differences between two proportions. RESULTS: The
      mortality rate was 22.8% (6250/27,514) admissions. The male to female ratio was
      1.7:1. Infections (20.2%) were the most common cause of death. However, chronic
      kidney disease was the single most common disease entity causing death (12.3%).
      Other important causes of death in order of prevalence were cerebrovascular
      accident (10.5%), acquired immune deficiency syndrome and tuberculosis either
      alone or as co-infection (10.3%), heart failure (8.8%), chronic liver disease
      (7.0%), septicemia (6.5%), respiratory failure (5.3%), diabetes mellitus (4.6%),
      cardiac arrhythmias (2.9%), and primary liver cell carcinoma (2.7%). There were
      few deaths from tetanus, malaria, typhoid fever, and coronary artery disease.
      CONCLUSION: Mortality is high in our medical wards and reflects the emerging
      trend of mixed disease spectrum comprising communicable and noncommunicable
      diseases.

PMID- 25385908
TI  - Mental disorders frequency alternative and complementary medicine usage among
      patients with hypertension and type 2 diabetes mellitus.
AB  - OBJECTIVES: Diabetes mellitus (DM) and hypertension (HT) are chronic disorders
      with which mental disorders may coexist and for which patients may resort to
      alternative medicine use. Alternative and complementary medicine is a treatment
      option that patients tend to use. This study is to determine the prevalence of
      mental disorders among patients diagnosed with DM and HT and their use of
      alternative medicine methods. Materials and Methods The study was conducted in a
      primary care setting. The data were collected from the Family Health Center No. 4
      at Etaankaya, Ankara, Turkey. It involved patients aged between 18 and 65, who
      were on follow-up treatment for DM and HT. Patients accepted to participate in
      the study were administered the sociodemographic data form, the Primary Care
      Evaluation of Mental Disorders (PRIME-MD) questionnaire and the alternative
      medicine inquiry form. PARTICIPANTS: One hundred and sixteen patients with HT and
      119 patients with DM (type 2) were recruited for the study. RESULTS: In this
      study, 47.4% of HT patients and 53.8% of the DM patients were diagnosed with a
      PRIME-MD. The most commonly encountered disorder was mood disorders, in 37.1% of
      the HT patients and 45.4% of the DM patients. In this study, four HT patients
      (0.3%) and no DM patients stated that they resorted to complimentary medicine,
      which can use be used alongside conventional medical treatment and may help to
      feel better and cope better with any chronic condition. All four HT patients were
      using multivitamin combinations to support the treatment. As the alternative
      medicine usage was described as treatment used instead of conventional medical
      treatment we did not find any patient using alternative medicine. CONCLUSIONS:
      Mental disorders may coexist with HT and DM. Some of the HT and DM patients
      suffering from a mental disorder seek psychiatric support, while others do not.
      We believe that it is important to examine patients for mental disorders, while
      being followed-up for a chronic disease.

PMID- 25385909
TI  - Making a difference with Vision 2020: The Right to Sight? Lessons from two states
      of North Western Nigeria.
AB  - Settings and Aim: The World Health Organization launched in 1999 an initiative to
      eliminate the global avoidable blindness and prevent the projected doubling of
      avoidable visual impairment between 1990 and 2020 (Vision 2020: The Right to
      Sight). The World Health Assembly (WHA) adopted resolutions WHA 59.25, WHA 56.26
      urging member states to adopt the Vision 2020 principles. More than 90
      nongovernmental development organizations, agencies, and institutions, together
      with a number of major corporations, are now working together in this global
      partnership. Two neighboring states in North Western Nigeria provide eye care
      services using different approaches; one state uses the principles of Vision
      2020, the other uses a different strategy. The aim of the study was to assess
      awareness and utilization of eye care services in two Nigerian states. DESIGN: A
      population-based cross-sectional interview of households was conducted in two
      neighboring states using a structured questionnaire. Data analysis was performed
      using SPSS version 21 and a P < 0.05 was considered as significant. FINDINGS:
      Participation rate was 97% in the two states. The population in the Vision 2020
      compliant state were significantly more aware about general eye care services
      (80% vs. 44%, P < 0.0005); had less proportion of households unaware of any eye
      care service (55% vs. 69%, P < 0.0005); and have a significantly higher felt the
      need to utilize eye care services (47% vs. 5.9%, P < 0.0005). The service
      utilization rate was however low in the two states. CONCLUSION: The principles of
      Vision 2020: The Right to Sight is adaptable to different cultures/societies and
      has demonstrated a potential to increase awareness and a felt need for eye care
      in poor resource settings.

PMID- 25385910
TI  - Assessment of physicians' knowledge of Glasgow coma score.
AB  - BACKGROUND: Glasgow Coma Scale (GCS) is the most commonly used tool in assessing
      comatose patients. It is simple, easily communicable, and useful in
      prognostication and determination of the treatment modality in head injury.
      Unfortunately, a high percentage of clinicians who are not in the emergency or
      neurological services are not conversant with this life-saving tool. OBJECTIVE:
      The objective of this study was to assess the level of knowledge of GCS among
      physicians practicing in a tertiary institution in South-East Nigeria, and to
      evaluate the call for a new and simpler scoring system. MATERIALS AND METHODS:
      This study was carried out using the instrument of a structured-questionnaire in
      Nnamdi Azikiwe University Teaching Hospital Nnewi, a federal government tertiary
      health institution in South-East Zone of Nigeria, which is a 350-bed facility
      employing about 550 medical doctors of different cadres. RESULTS: A total of 139
      questionnaires were distributed to the doctors practicing in the institution who
      consented to participating in the study. The questionnaires were completed at the
      point of their administration and completed questionnaires were retrieved on the
      spot, and data were collated, and analyzed with the Statistical Package for
      Social Sciences, SPSS version 17.0. Statistical significance was calculated with
      the chi square, P <= 0.5. The modal age group was 20-30 years 66 (48%), and most
      were resident doctors 99 (66.2%). One week prior to the questionnaire
      distribution, 56 (42.1%) had been actively involved in emergency care of
      patients, and 41 (30%) could not recall what GCS stood for. Medical and house
      officers showed a better knowledge of GCS. CONCLUSION: There was a poor knowledge
      of GCS among a good number of physicians practicing in our setting and hence,
      continuing medical education on GCS is strongly advocated.

PMID- 25385911
TI  - Effect of chronic kidney disease on serum resistin level.
AB  - BACKGROUND: Chronic Kidney Diseases (CKD) of all etiologies are usually
      associated with Insulin Resistance (IR). Resistin is also a protein associated
      with IR. Some studies conducted abroad have shown that resistin level is higher
      among CKD patients. OBJECTIVE: To test if serum resistin level is significantly
      higher in CKD patients compared to normal individuals. PATIENTS AND METHODS: 96
      CKD patients and 97 normal individuals were included in the study. Written
      informed consent was obtained from every individual. RESULTS: Serum resistin
      level was higher in CKD patients compared to control subjects. The difference in
      serum resistin level between two groups was statistically significant.
      CONCLUSION: Our study is probably the first study in India comparing serum
      resistin levels of CKD patients vis-a-vis control subjects. Further cellular
      research may be needed to explore this relation.

PMID- 25385912
TI  - The efficacy of chewing gum on postoperative ileus following cesarean section in
      Enugu, South East Nigeria: A randomized controlled clinical trial.
AB  - BACKGROUND: Postoperative ileus (POI) is a common complication following
      caesarean section. It impairs patients comfort; delays wound healing and prolong
      duration of hospital stay. Several methods have been used in the management of
      this condition with varying efficacy. Chewing gum postoperatively is a recent
      concept in the western world being advocated as a cost effective and comfortable
      management of POI. AIM: The aim was to evaluate the efficacy of gum-chewing in
      reducing POI following caesarean section in Enugu. MATERIALS AND METHODS: One
      hundred and eighty women booked for elective caesarean section were randomized
      into gum-chewing group (n = 90) or control group (n = 90) The subjects chewed
      sugarless gum three times daily from 6 h postoperatively until the first passage
      of flatus. Each chewing session lasted 30 min. Elective cesarean section was
      carried out with a Pfannenstiel incision. Groups were compared primarily for time
      to first bowel sound, and first flatus. Secondary endpoints of comparison were
      time of operation to first defecation, and patient satisfaction concerning
      postoperative gum chewing. The Student's t-test and Pearson Chi-square test and
      multiple linear regression were used for statistical analysis. RESULTS: The
      groups were comparable in age, body mass index (BMI) and duration of surgery. The
      mean time to first bowel sounds (21.9 +/- 8.0 vs. 26.1 +/- 10.0), mean time to
      first flatus (24.8 +/- 6.4 vs. 30.0 +/- 10.0) and mean time to defecation (30.7
      +/- 5.9 vs. 40.0 +/- 9.0) were significantly reduced in patients that chewed gum
      compared with controls. P =0.02, 0.01, and 0.01, respectively. Patients were
      satisfied with gum chewing and no side-effect was recorded. Previous surgery and
      duration of surgery were predictors on duration of POI, while age, BMI and parity
      had no effect. CONCLUSION: Gum-chewing has a beneficial effect on early return of
      bowel function following cesarean section and should be included in the
      postoperative management protocol.

PMID- 25385913
TI  - Obesity, overweight, and underweight among urban Nigerians.
AB  - BACKGROUND: Disease burden from communicable and noncommunicable diseases is a
      significant health challenge facing many developing nations. Among the
      noncommunicable diseases, is obesity, which has become a global epidemic
      associated with urbanization. OBJECTIVE: The aim was to evaluate the prevalence
      of weight abnormalities, their pattern of distribution and regional differences
      among apparently healthy urban dwelling Nigerians. METHODS: A cross-sectional
      community-based descriptive survey was carried out in five urban cities, each
      from one geo-political zone of Nigeria. Multistage sampling procedures were used
      to select participants using the World Health Organization STEPS instrument.
      Ethical approval and consents were duly and respectively obtained from the Ethics
      Committee in the tertiary centers and participants in each of these cities.
      Analysis was performed using SPSS version 20 (IBM Corp., Amonk, NY; released
      2011) with P value set at < 0.05. RESULTS: A total of 5392 participants were
      recruited; of which, 54.5% and 45.5% were males and females respectively. Mean
      (standard deviation) age and body mass index (BMI) were 40.6 (14.3) years and
      25.3 (5.1) kg/m 2 . Obesity, overweight, and underweight were found in 17%, 31%,
      and 5% of participants respectively. Significantly, while underweight declined
      with increasing age, overweight, and obesity increased to peak in the middle age
      brackets. Age of >= 40 years was found to confer about twice the risk of becoming
      overweight. The prevalence of obesity and mean BMI were significantly higher both
      among the females and the participants from southern zones. CONCLUSION: Obesity
      and overweight are common in our urban dwellers with accompanying regional
      differences. Attainment of middle age increases the likelihood of urban dwelling
      Nigerians to become overweight/obese. There is therefore the need to institute
      measures that will check development of overweight/obesity early enough, while
      improving the nutritional status of the few who may still be undernourished.

PMID- 25385914
TI  - Prevalence of traditional cardiovascular risk factors among staff of Ladoke
      Akintola University of Technology, Ogbomoso, Nigeria.
AB  - AIM: The aim was to describe the frequency of occurrence of traditional
      cardiovascular (CV) risk factors among selected university workers in Ladoke
      Akintola University of Technology (LAUTECH) Nigeria. MATERIALS AND METHODS: A
      cross-sectional study of 206 staff of LAUTECH, Ogbomoso, Nigeria had an
      assessment for nine traditional CV risk factors. Demographic and clinical
      parameters were taken. Blood sample was taken to determine the random blood sugar
      and lipid profile. 12-lead resting electrocardiography (ECG) was done for all
      participants. Statistical analysis was performed with the aid of Statistical
      Package for Social Sciences (SPSS) version 17.0 (Chicago Ill., USA) Results: The
      study population included 96 males (46.6%) and 110 females. The mean age was 45.3
      +/- 7.9 years (range 27-73 years). The prevalence of CV risk factors were as
      follows: Hypertension 84 (40.8%), visceral obesity 92 (44.7%), generalized
      obesity 79 (38.3%), low high density lipoprotein 113 (54.9%), impaired blood
      glucose 16 (7.8%), diabetes mellitus 3 (1.5%), hypercholesterolemia 102 (49.5%),
      left ventricular hypertrophy-ECG 24 (11.7%), elevated low density lipoprotein
      cholesterol 99 (48.1%). About - (72.3%) had two or more CV risk factors clustered
      together. Females had a higher prevalence of CV risk factors and its clusters
      than their male counterparts. Of those diagnosed with hypertension in this study,
      more than half had never been told they were hypertensive 48 (57.1%). CONCLUSION:
      This study suggests a very high prevalence of CV risk factors among University
      Staff in LAUTECH, Ogbomoso, Nigeria. Clustering of CV risk factors is more
      prevalent among women. Appropriate preventive strategy in terms of education and
      modification of risk factors are important to reduce the burden of CV diseases
      among this population.

PMID- 25385915
TI  - Polyp prevalence at colonoscopy among Nigerians: A prospective observational
      study.
AB  - BACKGROUND: This study was aimed at identifying the prevalence, distribution, and
      clinicopathologic characteristic of colonic polyps among Nigerians undergoing
      colonoscopy at the Obafemi Awolowo University Teaching Hospitals complex, Ile
      Ife, Nigeria. We also determined the polyp detection rate (PDR), polyps per
      colonoscopy (PPC) and adenoma detection rate (ADR). MATERIALS AND METHODS: This
      is a prospective study of all colonoscopy examinations performed at the endoscopy
      unit of our hospital from January, 2007 to December 2013. The patient
      demographics, indications for colonoscopy, colonoscopic findings, number of the
      polyps, their sizes, possible risk factors in the individual case histories, and
      histopathological characteristics of the polyps. RESULTS: During the study
      period, a total of 415 patients met the inclusion criteria and only 67 out of
      these had colonic polyps. The overall PDR was 16.1%. The age ranged was 2-87
      years with a median of 57 years. Forty-three (64.2%) patients were 50 years or
      above and there were 40 (59.7%) males. Thirty-three (49.3%) patients were
      referred as a result of lower gastrointestinal bleeding, 14 (20.9%) for
      colorectal cancer (CRC) and 13 (19.4%) for routine screening. Thirty-nine (58.2%)
      patients had the polyps at the rectosigmoid region of the colon, 17 (25.4%) had
      the polyps located proximal to sigmoid colon and 11 (16.4%) patients had multiple
      polyps involving both segments. Adenomatous polyps was the most common (28
      [47.5%]) histopathological finding of which two patients had adenomatous
      polyposis. Other findings include inflammatory polyps in 17 (18.8%) patients, 5
      (8.5%) patients each had hyperplastic and malignant polyps, while 4 (6.8%)
      patients had juvenile polyps. The ADR was 6.8 and the PPC was 0.2. Statistically,
      patients 50 years and older were more likely to have adenomatous and hyperplastic
      polyps than those younger than this age (P = 0.010). CONCLUSION: We conclude that
      polyps are probably not as rare among black Africans especially when they are
      above 50 years. Our histopathological finding of adenomatous change in a good
      proportion of the detected polyps show that they are likely to be associated with
      CRCs in our compatriots and as such we would recommend a routine screening
      colonoscopy for Nigerians aged 50 and above.

PMID- 25385916
TI  - Traumatic penile injuries: Mechanisms and problems of treatment in a tertiary
      institution in Nigeria.
AB  - BACKGROUND: Penile injuries are uncommon. The more severe injuries are often
      difficult to manage. OBJECTIVES: We report our experience with penile injuries
      from different causes and treatment options available. PATIENTS AND METHODS: We
      analyzed retrospectively 23 cases of penile injuries presenting to the Urology
      Unit of a tertiary hospital in the Southeastern part of Nigeria from January 2007
      to December 2012. RESULTS: The management for each patient varied depending on
      the nature and extent of the injury. The mean age of the patients was 28.9 +/-
      14.4 years (range 3 weeks to 43 years). The mean duration before presentation was
      22.7 +/- 17.8 h (range 1-168 h). The causes of penile injuries were categorized
      as follows: Postcircumcision 3 (13.0%), genital mutilation (self-inflicted
      injury/attacks by assailants) 6 (26.1%), accident 4 (17.4%), penile fracture 8
      (34.8%), and gunshot injury 2 (8.6%). Isolated blunt injuries to the corporal
      tissues as occurs in penile fractures was managed successfully with early
      exploration and closure of the tunical tear, while injuries to the penile skin
      was managed with dressing and secondary closure. Severe penile injuries resulting
      in partial or total phallic loss presented the most challenge to treatment.
      CONCLUSION: Traumatic penile injuries are not common. Severe penile injuries
      could be challenging because of the nature of the injuries, delayed presentation
      and unavailability of modern technological tools and experience required for the
      treatment of such severe injuries. Expertise in the use of flaps for a neophallus
      are still been developed, and penile prosthetic devices are not readily available
      in our setting.

PMID- 25385917
TI  - Nonoperative treatment of acute traumatic spinal injuries: A prospective study.
AB  - BACKGROUND: Traumatic spinal injury is a major cause of morbidity and mortality
      worldwide. There is no agreed method of care. Neurological recovery in complete
      injury has been dismal. Aims and Objectives : The aim of this study is to
      determine the neurological recovery at discharge in traumatic spinal injury
      patients managed nonoperatively in our center. MATERIALS AND METHODS: This was a
      prospective descriptive study carried out on traumatic spinal injury patients
      managed by neurosurgical unit in our center from August 2010 to July 2013. The
      unit started in July 2010 with virtually no available facilities for surgical
      care for these patients. All patients were managed nonoperatively. The unit
      recorded data of the patients in accident and emergency, intensive care unit, and
      wards using structured proforma. Data were analyzed using Epi Info 7 software.
      RESULTS: There were 76 patients studied of which 57 were males and 25 were
      females. Fifty three were caused by road traffic accident. Nineteen were complete
      injury. Patients with incomplete injuries did well at discharge. Completeness of
      injury significantly affected the outcome. CONCLUSION: The neurological recovery
      in incomplete spinal injuries in our study was good, but poor in complete injury.
      Conservative treatment should be adopted in developing countries in patients with
      poor resources and in centers where facilities are not available for adequate
      imaging and surgical care. Trauma system is imperative in our country.

PMID- 25385918
TI  - Evaluation of radiographic features of embedded primary molar roots in adult
      Turkish population.
AB  - BACKGROUND: The roots of primary molars were found in the permanent dentition
      without symptoms on the clinical or radiographic examination. However, their
      incidence could not be achieved on the current literature. OBJECTIVE: The aim of
      this study is to evaluate the radiographic features of the embedded primary molar
      roots in adult dentulous patients in Turkey. MATERIALS AND METHODS: The data,
      from 5000 adult patients, including panoramic radiographs and demographic
      information, were evaluated retrospectively. The prevalence and location of the
      primary molar roots in the jaws were determined, as well as the prevalence and
      location of the primary molar roots in the adjacent permanent root levels.
      RESULTS: Among 5000 Turkish population dentulous patients, 20 retained primary
      molar roots (0.38%) were found in 19 ones. CONCLUSIONS: The prevalence of the
      primary molar roots in the present study was found to be lower than that of the
      previous study. This finding may result from the larger amount of patient data
      that was evaluated in this study, which used panoramic radiographs.

PMID- 25385919
TI  - Investigation of biofilm formation on contact eye lenses caused by methicillin
      resistant Staphylococcus aureus.
AB  - OBJECTIVE: The objective was to investigate the biofilm-forming capacity of
      methicillin resistant Staphylococcus aureus (MRSA) isolated from eye lenses of
      infected patients. MATERIALS AND METHODS: A total of 32 MRSA isolated from
      contact lenses of patients with ocular infections were screened for their biofilm
      forming capacity using tube method (TM), Congo red agar (CRA), and microtiter
      plate (MtP) methods. The effect of some stress factor on the biofilm formation
      was studied. The biofilm-forming related genes, icaA, icaD and 10 microbial
      surface components that recognize adhesive matrix molecule (MSCRAMM), of the
      selected MRSA were also detected using polymerase chain reaction. RESULTS: Of 32
      MRSA isolates, 34.37%, 59.37%, and 81.25% showed positive results using CRA, TM
      or MtP, respectively. Biofilm production was found to be reduced in the presence
      of ethanol or ethylenediaminetetraacetic acid and at extreme pH values. On the
      other hand, glucose or heparin leads to a concentration dependent increase of
      biofilm production by the isolates. The selected biofilm producing MRSA isolate
      was found to harbor the icaA, icaD and up to nine of 10 tested MSCRAMM genes,
      whereas the selected non biofilm producing MRSA isolate did not carry any of the
      tested genes. CONCLUSIONS: The MtP method was found to be the most effective
      phenotypic screening method for detection of biofilm formation by MRSA.
      Furthermore, the molecular approach should be taken into consideration for the
      rapid and correct diagnosis of virulent bacteria associated with contact eye
      lenses.

PMID- 25385920
TI  - Determinants of timely initiation of complementary feeding among children aged 6
      24 months in Sagamu, Nigeria.
AB  - BACKGROUND: Poor breastfeeding and complementary feeding practices may contribute
      to childhood malnutrition in the developing world. OBJECTIVE: The objective was
      to examine the determinants of timely initiation of complementary feeding among
      Nigerian children. MATERIALS AND METHODS: Using a cross-sectional design,
      children aged 6-24 months were surveyed in a Nigerian Teaching Hospital. Children
      with timely initiation of complementary feeding (6-8 months) were compared with
      children with untimely initiation of complementary feeding early (<6 months and
      >8 months) for clinical and social characteristics using both bivariate and
      multivariate analysis. RESULTS: Of 156 children, 41%, 53.8%, and 5.1% had timely,
      early and delayed initiation of complementary feeding. Complementary feeding was
      initiated with processed cereals (44.8%), locally prepared maize gruel (32.1%)
      and mashed family diet (23.1%). Bivariate analysis showed significant association
      between timely initiation of complementary and orthodox maternity care, no
      prelacteal feeding, exclusive breastfeeding, no siblings and first birth order.
      Parental education was not associated with timely initiation of complementary
      feeding. Multivariate analysis identified orthodox maternity care, exclusive
      breastfeeding and no siblings as independent predictors of timely initiation of
      complementary feeding. CONCLUSION: Complementary feeding is most frequently
      initiated earlier than 6 months in this population. Good breastfeeding practices
      may influence timely initiation of complementary feeding. Interventions should be
      targeted at the entire population irrespective of educational and socioeconomic
      status.

PMID- 25385921
TI  - Prevalence of sexual dysfunction among females in a university community in
      Enugu, Nigeria.
AB  - BACKGROUND: Female sexual dysfunction is a common, condition that significantly
      reduces the quality-of-life of the affected persons. Unfortunately, because of
      the veil of secrecy that shrouds discussions on human sexuality, there has been
      limited research on this topic in some sociocultural settings. AIM: The aim was
      to determine the prevalence and some sociodemographic factors associated with
      sexual dysfunction in females in a university community at the University of
      Nigeria, Enugu Campus, Enugu State, Nigeria. SUBJECTS AND METHODS: This is a
      cross-sectional study involving 500 females recruited randomly in a tertiary
      institution in Nigeria. A self-administered structured pretested questionnaire on
      sexual activity was administered (the Female Sexual Function Index [FSFI]).
      Statistical analysis was performed using SPSS software package (Version 17.0,
      Chicago, IL, USA). Multiple logistic regression was used to determine the
      relationship between the sociodemographic factors, and the total FSFI scores
      dichotomized as normal and reduced sexual function. In addition, multiple linear
      regression was used to determine the relationship between the six different
      domains scores and the continuous values of the total score. For all,
      calculations, P < 0.05 was considered as statistically significant at 95%
      confidence interval (CI). RESULTS: The prevalence of female sexual dysfunction
      (FSFI score <= 26.50) was 53.3%. The highest prevalence occurred in the 41-50
      years age group (73.3%; 66/90), married and living together 56.4% (123/218) and
      had postsecondary education (56.1%; 137/244). Only age significantly predicted
      female sexual function (P = 0.007; 95% CI; 0.691-0.943). Marital status,
      religion, ethnic group, and educational qualification had no significant effect
      (P < 0.05). The total FSFI significantly increase as desire increases (P = 0.002;
      95% CI = 0.817-3.573). CONCLUSION: Female sexual dysfunction is common in the
      university environment, with the highest prevalence occurring in 41-50 years age
      group.

PMID- 25385922
TI  - Transvesical prostatectomy in the management of benign prostatic hyperplasia in a
      developing country.
AB  - CONTEXT: The surgical management of benign prostatic hyperplasia (BPH) is
      evolving away from open surgery. In developing countries however majority of
      cases are managed by transvesical prostatectomy (TP). AIMS: This study aims to
      describe our experience regarding the efficacy, complication profile and outcome
      of TP in the management of BPH in Nigeria. SETTINGS AND DESIGN: A descriptive,
      retrospective study carried out in three tertiary centers. SUBJECTS AND METHODS:
      Two hundred and ninety-seven patients were studied. Parameters examined included
      age, clinical features, investigations, type of postoperative bladder irrigation,
      prostate gland volume, duration of hospital stay, complications and outcome.
      STATISTICAL ANALYSIS USED: Simple means and percentages with SPSS 16. RESULTS:
      Mean age was 65.2 +/- 6.8 years (range 47-93 years). Presentation with severe
      lower urinary tract symptoms only occurred in 76 patients (25.7%); acute urinary
      retention was seen in 106 patients (35.7%). Chronic urinary retention, impaired
      renal function and haematuria occurred in 47 (15.8%), 37 (12.5%), and 31 patients
      (10.4%) respectively. On comorbidity, 63 patients (21.2%) were hypertensive and
      24 patients (8.1%) had diabetes mellitus. Two hundred and twenty three patients
      (75%) had indwelling catheters at the time of surgery. Preoperative urinary
      catheter duration was 1 week-35 months. Mean duration of hospital stay was 8.8
      days. Complications were transient urinary incontinence 33 patients (11.1%),
      urinary tract infection 38 patients (12.7%), and acute epididymoorchitis 15
      patients (5.1%). Clot retention occurred in 40 patients (13.5%). Mortality rate
      was 1%. CONCLUSIONS: TP remains useful in developing climes. There is a need to
      emphasize effective preoperative workup so as to limit morbidity. Emphasis on
      variety of techniques for hemostasis is necessary.

PMID- 25385923
TI  - Awareness and practice of breast screening and its impact on early detection and
      presentation among breast cancer patients attending a clinic in Lagos, Nigeria.
AB  - BACKGROUND: Breast cancer is the most common malignancy among females in Nigeria.
      The concept of breast screening (BS) is that it would result in presentation at
      earlier stages. We evaluated the impact of BS on early detection and presentation
      of breast cancer and determined the aspects BS need improvement. PATIENTS AND
      METHODS: All patients with a diagnosis of malignant breast lump attending clinics
      at a tertiary hospital in Nigeria were recruited into the study over a 2-year
      period. Self-administered questionnaires were given to patients. Data collected
      were demographics, knowledge about BS, practice of BS, the motivation to practice
      BS and the source of information on BS. RESULTS: Of 218 patients seen, 147
      (67.4%) patients presented at the surgical outpatient clinic and 71 (32.6%) at
      the radiotherapy clinic, with age 48.01 +/- 0.80 years. A total of 156 (71.6%)
      were aware of BS, while 62 (28.4%) were not aware. A logistic regression analysis
      showed that only the level of formal education predicted awareness of BS, P =
      0.001 Nagelkerke's R2 = 0.126. Awareness of BS was mainly from electronic media
      87 (55.7%). There was no significant difference in the ages of those aware and
      practicing BS 48.03 +/- 1.05 years, and those not practicing BS 46.32 +/- 1.94
      years, P = 0.446. There was no significant difference in presentation for those
      practicing BS 7.41 +/- 1.30 months, and those not practicing BS 11.38 +/- 2.91
      months, P = 0.175, with 64% practicing BS presenting late, while 77% not
      practicing BS presenting late, chi2 = 2.432, P = 0.488. A logistic regression
      analysis did not show any demographic or clinical parameters as predictive P =
      0.225 Nagelkerke's R2 = 0.126. CONCLUSION: The high level of awareness and
      practice of BS was not translated into the presentation with early breast cancer.

PMID- 25385924
TI  - Experiences from polio supplementary immunization activities in Anambra State,
      Nigeria.
AB  - BACKGROUND: Routine immunization coverage is low in some States in Nigeria and
      contributes to the transmission of wild poliovirus. Anambra State has been polio
      free since 2004. However, the risk of importation of poliovirus from travelers
      and migrants is a public health concern due to the commercial nature of the
      State. This paper reported experiences and lessons from supplementary
      immunization activities (SIAs) conducted in the State that will be useful to
      other settings experiencing low uptake of routine immunization. MATERIALS AND
      METHODS: The SIAs were conducted simultaneously in the 21 local government areas
      (LGAs) in Anambra State during January, March, and November 2010. Data were
      entered and analyzed in Excel spreadsheet and findings were summarized as
      frequencies and proportions. RESULTS: A total of 1,187,866 children were
      vaccinated in January, 1,260,876 in March and 1,225,187 in November 2010. The
      State's cumulative coverage exceeded the target coverage of >90% in the three
      SIAs. All LGAs met the >90% target in January and March, but one LGA achieved 79%
      coverage in November. The proportion of zero-dose children decreased from 6% to
      4.7%, and the vaccine wastage rate ranged from 6% to 6.6%. In that same year, the
      state did not achieve the target coverage of >80% for routine oral polio vaccine
      (OPV 3 ) immunization in any of the months and only 29% of the LGAs exceeded the
      routine OPV 3 target. CONCLUSION: The State achieved high polio vaccination
      coverage through the SIAs, but coverage through routine immunization was low.
      Adopting proper planning and supervision, financial and political support,
      community involvement, improved vaccine logistics, and other measures utilized
      during the SIAs could help to improve routine immunization.

PMID- 25385925
TI  - An ectopic hamartomatous thymoma compressing left jugular vein.
AB  - Ectopic hamartomatous thymoma (EHT) is an extremely rare benign neoplasm. It is
      usually found at the root of the neck (frequently on the left) and does not
      usually impact adjacent tissues in clinically significant ways. While EHT
      manifests distinct pathological features, the lesion is either asymptomatic or
      may show nonspecific clinical features. We report one case of EHT which was
      assumed to be of low malignant potential since it severely compressed the inlet
      of left internal jugular vein as seen by computed tomography scan. To the best of
      our knowledge, this clinical finding of EHT is very rare. After the diagnosis and
      treatment of this patient, we believe that EHT or suspected EHT should be treated
      less invasively.

PMID- 25385926
TI  - A rare cause of blepharoconjunctivitis: Phthiriasis palpebrarum.

PMID- 25385927
TI  - Lessons from Ramazzini for occupational health in the Asia-Pacific region.

PMID- 25385929
TI  - Decolonization of children after incision and drainage for MRSA abscess: a
      retrospective cohort study.
AB  - BACKGROUND/PURPOSE: Whether decolonization following incision and drainage (I&D)
      for methicillin-resistant Staphylococcus aureus (MRSA) abscess decreases repeat
      I&D and MRSA-positive cultures in children is unknown. MATERIALS/METHODS:
      Referral to the Pediatric Infectious Disease Service (PIDS) for decolonization
      was determined for eligible children (2003-2010), with outcomes studied over 12
      months. RESULTS: We identified 653 children; 54 had been seen by PIDS. In the
      PIDS group, no patients (0/54, 0%) had a repeat I&D. In the no PIDS group 36/599
      (6%) had a repeat I&D, P = .06. Logistic regression modeling for repeat I&D
      showed no significant effect, odds ratio = 0.29; 95% confidence interval = 0.04
      2.15; P = .23. In the PIDS group, 3 patients (3/54, 5.6%) had a repeat MRSA
      positive culture. In the no PIDS group, 58/599 (9.7%) had a positive repeat
      culture, P = .46. Logistic regression modeling for positive culture showed no
      significant effect (odds ratio = 0.55; 95% confidence interval = 0.17-1.81; P =
      .32). CONCLUSIONS: We detected no statistically significant association between
      decolonization and repeat I&D or MRSA-positive culture.

PMID- 25385930
TI  - Pediatric Provider Insight Into Newborn Screening for Glucose-6-Phosphate
      Dehydrogenase Deficiency.
AB  - OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a major
      contributor to neonatal hyperbilirubinemia, yet newborn screening for this
      disorder in the United States is not standard practice. We surveyed pediatric
      providers regarding a novel newborn G6PD screening program successfully
      implemented in 2007 at a US urban women's hospital newborn nursery. STUDY DESIGN:
      An electronic survey was distributed to 472 pediatric providers addressing extent
      to which they were influenced by the screening program. RESULTS: Ninety-two (20%)
      providers responded, of whom 74 (80%) had taken care of G6PD-deficient patients
      diagnosed by the screening program. A majority found the diagnosis helpful for
      patient management and influential in their management. Most common changes in
      management included more counseling on jaundice and follow-up and avoidance of
      hemolytic crisis triggers. CONCLUSIONS: General pediatric providers support
      newborn G6PD screening and appreciate the current program. Knowing the G6PD
      deficiency status of newborns informed and influenced pediatric providers' care.

PMID- 25385931
TI  - Communication From Primary Care Practices Regarding Adolescent Immunization.

PMID- 25385932
TI  - Association between sleep bruxism and psychosocial factors in children and
      adolescents: a systematic review.
AB  - OBJECTIVE: To summarize the association between sleep bruxism and psychosocial
      factors in children and adolescents. DESIGN: Individual search strategies for
      five databases were developed. The references cited in the selected articles were
      checked and a partial gray literature search was undertaken. Only articles that
      used the international diagnostic criteria for sleep bruxism as proposed by the
      American Association of Sleep Medicine were included. Any form of reporting of
      psychosocial factors was considered. RESULTS: Of the 44 retained articles, only 7
      studies were finally included for the qualitative/quantitative synthesis. No
      evidence supportive of an association between sleep bruxism and psychosocial
      factors in children younger than 5 years emerged. A significant association was
      present in children between 6 and 11 years old and in adolescents 12 to 17 years
      old. Risk of bias was low-to-moderate in most of the included studies.
      CONCLUSION: The current available evidence suggests an association between sleep
      bruxism and psychological factors in children older than 6 years.

PMID- 25385933
TI  - Community-acquired urinary tract infection in hospitalized children: etiology and
      antimicrobial resistance. A comparison between first episode and recurrent
      infection.
AB  - Urinary tract infection (UTI) is common in infants and children, and Escherichia
      coli is the leading pathogen. The aims of this study were to compare first
      episode of UTI with recurrent infection, reveal organisms that cause UTI,
      uropathogen resistance, and presence of bacteria producing extended-spectrum beta
      lactamase (ESBL). The first-UTI group included 456 children. E coli was the
      leading pathogen (80.5%), and Pseudomonas aeruginosa was found in 1.5%. The
      uropathogens were resistant to gentamicin (3.41%) and cefuroxime (5.71%), and
      highly resistant to cefamezin (37.39%). The recurrent-infection group included
      106 children. E coli was also the leading pathogen, but 7.5% of the isolates were
      P aeruginosa (P = .002 compared with first-episode group); 6.6% were ESBL
      producing bacteria compared with 1.1% in the first-episode group (P = .002). E
      coli is the leading pathogen in both groups. P aeruginosa and ESBL-producing
      bacteria were more common in the recurrent infection group. 

PMID- 25385934
TI  - Evaluating surrogate endpoints, prognostic markers, and predictive markers: Some
      simple themes.
AB  - BACKGROUND: A surrogate endpoint is an endpoint observed earlier than the true
      endpoint (a health outcome) that is used to draw conclusions about the effect of
      treatment on the unobserved true endpoint. A prognostic marker is a marker for
      predicting the risk of an event given a control treatment; it informs treatment
      decisions when there is information on anticipated benefits and harms of a new
      treatment applied to persons at high risk. A predictive marker is a marker for
      predicting the effect of treatment on outcome in a subgroup of patients or study
      participants; it provides more rigorous information for treatment selection than
      a prognostic marker when it is based on estimated treatment effects in a
      randomized trial. METHODS: We organized our discussion around a different theme
      for each topic. RESULTS: "Fundamentally an extrapolation" refers to the non
      statistical considerations and assumptions needed when using surrogate endpoints
      to evaluate a new treatment. "Decision analysis to the rescue" refers to use the
      use of decision analysis to evaluate an additional prognostic marker because it
      is not possible to choose between purely statistical measures of marker
      performance. "The appeal of simplicity" refers to a straightforward and efficient
      use of a single randomized trial to evaluate overall treatment effect and
      treatment effect within subgroups using predictive markers. CONCLUSION: The
      simple themes provide a general guideline for evaluation of surrogate endpoints,
      prognostic markers, and predictive markers.

PMID- 25385936
TI  - Savings precede spending: fatty acid utilization relies on triglyceride formation
      for cardiac energetics.

PMID- 25385937
TI  - Clinical diagnosis of pulmonary hypertension.

PMID- 25385939
TI  - Extracellular volume imaging and quantitative T2 mapping for the diagnosis of
      mitochondrial cardiomyopathy.

PMID- 25385940
TI  - Percutaneous edge-to-edge mitral valve repair escorted by left atrial
      intracardiac echocardiography (ICE).

PMID- 25385941
TI  - Supporting development in children with congenital heart disease. Cardiology
      Patient Page.

PMID- 25385942
TI  - Letter by Ehdaie and Rubin regarding article, "Long-term arrhythmia-free survival
      in patients with severe left ventricular dysfunction and no inducible ventricular
      tachycardia after myocardial infarction".

PMID- 25385943
TI  - Letter by Ferrari et al regarding article, "Long-term arrhythmia-free survival in
      patients with severe left ventricular dysfunction and no inducible ventricular
      tachycardia after myocardial infarction".

PMID- 25385944
TI  - Response to letters regarding article, "long-term arrhythmia-free survival in
      patients with severe left ventricular dysfunction and no inducible ventricular
      tachycardia after myocardial infarction".

PMID- 25385945
TI  - Are you ready for more insulin concentrations?
AB  - Practitioners need to prepare for a rapid expansion of new concentrated insulins.
      For many years, the treatment regimens for patients have been limited to 2
      concentrations (100 units/mL and 500 units/mL), which pose challenges to both
      patients and providers. As the new concentrated insulins are at various stages of
      development, this manuscript reviews the available information on the new
      concentrated products. This information was obtained from publications, poster
      presentations, abstracts, and the manufacturers for the products in earlier
      stages of development. To have a basis for comparison, it is important to
      understand the activity profile and the challenges with use of the currently
      available concentrated insulin, regular insulin 500 units/mL (U500R). We also
      examine how the newer products may assist clinicians and patients with the
      difficulties faced with the use of U500R. 

PMID- 25385946
TI  - Intranasal glucagon: a promising approach for treatment of severe hypoglycemia.
AB  - Prevention of diabetic complications is mainly obtained through optimal control
      of blood glucose levels. With hypoglycemic drugs like beta-cell stimulating drugs
      and especially insulin, the limit to treatment is represented by hypoglycemia, a
      life-threatening occurrence that is dangerous itself and can induce fear of other
      episodes. Glucagon, injected subcutaneously (SC) or intramuscularly (IM), is the
      treatment of choice for severe hypoglycemia outside of the hospital setting.
      However, due to practical aspects such as preparation of solutions for
      administration and injection by untrained persons, there are obstacles to its
      routine use. This review focuses on the current status of alternative routes of
      administration of peptide hormones, and in particular the intranasal (IN) route
      of glucagon, as a promising approach for the treatment of severe hypoglycemia. 

PMID- 25385947
TI  - Perceived accuracy in continuous glucose monitoring: understanding the impact on
      patients.
AB  - In terms of accuracy and reliability, the technology of real-time (RT) continuous
      glucose monitoring (CGM) is advancing quickly. Still, current devices are
      imperfect; as a result, patient complaints and frustrations are not uncommon. How
      do patients' perceptions of device accuracy affect their experience with RT-CGM?
      In this article, we argue that patients' satisfaction, or dissatisfaction, with
      accuracy has a major impact on how much they are likely to trust the device and
      how confident they may feel in using the information that is displayed. The
      available data suggest that greater satisfaction with accuracy is linked to
      better RT-CGM adherence, more confident and aggressive insulin adjustments,
      improvements in quality of life, reduced reliance on self-monitoring of blood
      glucose, and--potentially--less alarm fatigue. As the technology continues to
      mature, RT-CGM will become increasingly accurate and patients' confidence and
      trust in the available devices will likely grow, leading to greater uptake and
      more proactive use of RT-CGM.

PMID- 25385952
TI  - Growth characteristics of NaCl-selected and nonselected cells of Nicotiana
      tabacum L.
AB  - A cell line of Nicotiana tabacum L. var. Wisconsin 38 was selected (S-10 cells)
      which is capable of growth in medium containing 10 g liter(-1) NaCl. The fresh
      and dry weights of S-10 cells at stationary phase in medium containing 10 g
      liter(-1) NaCl were about 60 and 100% respectively, of that of S-10 cells grown
      without NaCl. When cells normally maintained in the absence of the salt (S-0
      cells) were transferred to medium containing 10 g liter(-1) NaCl, they underwent
      a 14-day lag period before growth could be detected and they reached stationary
      phase 36 days after inoculation compared to 14 days for S-10 cells. At stationary
      phase, fresh and dry weights of S-0 and S-10 cells were the same in the presence
      of salt. The S-0 cells exhibited a reduced growth rate once growth began in
      medium with 10 g liter(-1) NaCl. The cell mass doubling time of S-0 cells in
      medium with 10 g liter(-1) NaCl was 4 days compared to 1.2 days for these cells
      grown in the absence of the salt and 1.6 days for S-10 cells grown in medium with
      10 g liter(-1) NaCl. The resistance of the salt-selected cells was stable in the
      presence of the salt. However, after 5 cell mass doublings following transfer
      into medium without NaCl, these cells lost their resistance to salt and responded
      to NaCl like the cell population (S-0 cells) which had not been selected for
      growth on NaCl. 

PMID- 25385953
TI  - Phosphorylation of ribosomal proteins by cyclic AMP independent protein kinase
      (ribosomal casein kinase) from soybean cotyledons (Glycine max L.).
AB  - Ribosomal subunits prepared by zonal centrifugation of 80 S ribosomes from 1-day
      old soybean cotyledons were active in in vitro polyphenylalanine synthesis. 40 S
      and 60 S subunits contained 32 and 43 ribosomal proteins respectively, when
      analyzed by two-dimensional polyacrylamide gel electrophoresis. A cyclic AMP
      (cAMP) independent protein kinase associated with ribosomes was isolated from the
      ribosomal salt wash fraction and was found to be similar in chromatographic
      properties and substrate requirements to cAMP independent casein kinase II
      present in post-ribosomal supernatant. Soybean cotyledon ribosomal casein kinase
      in vitro phosphorylates 4 polypeptides of 40 S ribosomal subunit. 

PMID- 25385954
TI  - Transfer of nitrogen and carbon from a mature sunflower leaf-15NO2 and 13CO2
      feeding studies.
AB  - To investigate the long-distance transport of nitrogen and carbon from mature
      leaves, two stable isotopes, (15)N and (13)C, were introduced to a single mature
      sunflower leaf for less than 2 hr in the forms of NO2 and CO2, and the fate of
      (15)N and (13)C in plants was followed. In the first experiment, about 4 ppm
      (15)NO2 was applied to a mature sunflower leaf for 65 min in light, and the fate
      of (15)N was followed over 72 hr. (15)NO2 absorbed in sunflower was first
      incorporated into the ethanol-soluble fraction, then gradually incorporated into
      the ethanol-insoluble fraction: after 24 hr, only 12% remained in the soluble
      fraction in the fed leaf. Some (15)N was transferred from the fed leaf, first to
      the stems and next to the young growing leaves and roots, although negligible
      transfer to other mature leaves was detected. In the second experiment, 3.1 ppm
      (15)NO2 and 300-400 ppm (13)CO2 were simultaneously introduced to a single mature
      leaf for 110 min in light, and the fate of the two isotopes was followed for 28
      days. Most of the (13)C transfer from the fed leaf took place within 1 day,
      whereas the transfer of (15)N continued gradually during the experimental period
      after a small rapid transfer within 1 day. Just after isotope feeding, the ratios
      of transferred (13)C to (15)N were high in all parts and remained high in the
      lower stem and the root, although they decreased very rapidly in the upper leaves
      and the upper stem. In the root, (15)N did not show a significant loss while some
      (13)C loss occurred during the experimental period. The transfer of (13)C and
      (15)N to the lower leaves was very low. (13)C Studies showed that carbon of the
      flower originated from both reserved carbon and current photosynthates. 

PMID- 25385955
TI  - Hemicellulose of the pollen tube wall of Camellia japonica.
AB  - Successive fractionation of the pollen tube wall polysaccharides of Camellia
      japonica was carried out to analyze the sugar composition of each fraction. The
      hemicellulose fraction extracted with dimethylsulfoxide accounted for about 47%
      of the pollen tube wall. A purified preparation of this fraction was comprised
      essentially of glucose. A low specific rotation ([alpha]d = +6 degrees  in 1 n
      NaOH) and an absorption at 890 cm(-1) of the purified glucan indicated the beta
      configuration. This glucan was shown to be a callose-like beta-1,3-d-glucan by
      periodate oxidation, Smith degradation and methylation studies. The degree of
      polymerization of the glucan was calculated to be 21 from methylation analysis
      and determination of the reducing end-group. 

PMID- 25385956
TI  - Studies on the production of Digitalis cardenolides by plant tissue culture I.
      Determination of digitoxin and digoxin contents in first and second passage calli
      and organ redifferentiating calli of several Digitalis species by
      radioimmunoassay.
AB  - With first and second passage calli induced from seedlings of Digitalis purpurea,
      D. lanata, D. lutea, D. mertonensis, D. ambigua and D. ferruginea Gigantea and
      those induced from leaf discs of D. purpurea and D. lanata, the contents of
      digitoxin and digoxin equivalents were assayed and compared with the contents
      involved in the inocula. Although the total contents of digitoxin and digoxin
      equivalents in the first passage calli induced from seedlings varied between zero
      and nine times as high as in the original seedlings, those in the second passage
      calli were almost undetectable. The total contents of digitoxin equivalents in
      the first passage calli induced from leaf discs of D. purpurea were approximately
      equal to those in the original leaf discs, but those in the second passage calli
      were less than those in the inocula. In the first passage calli induced from leaf
      discs of D. lanata, the total contents of digitoxin equivalents decreased but
      those of digoxin equivalents slightly increased. However, in the second passage
      calli, the amounts of both cardenolides decreased. Root-forming calli accumulated
      no more digitoxin nor digoxin equivalents than completely dedifferentiated calli.
      However, shoot-forming calli accumulated considerable amounts of cardenolides,
      which were assayed as digitoxin and digoxin equivalents by radioimmunoassay. 

PMID- 25385957
TI  - Xyloglucan from suspension-cultured soybean cells.
AB  - Two kinds of xyloglucans were obtained from the cell walls of suspension-cultured
      soybean cells together with an additional one from the culture medium. They had
      almost the same properties, i.e., sugar composition, [alpha]d value, and iodine
      staining spectrum. The molecular weights of the two kinds of wall xyloglucans
      were 180,000 and 60,000, whereas that of the extracellular xyloglucan shifted
      from 60,000 to 30,000 with the progress of cultivation. The results from
      methylation analysis and fragmentation analysis with endoglucanase indicated that
      each xyloglucan was mainly constructed of two kinds of oligosaccharide repeating
      units, a heptasaccharide (glucose/xylose, 4 : 3) and a nonasaccharide
      (glucose/xylose/galactose/fucose, 4 : 3 : 1 : 1). Although the amount of wall
      xyloglucan increased during cell growth, the ratio of xyloglucan to total
      hemicellulose remained constant at about 50%. 

PMID- 25385958
TI  - Importance of RNA synthesis whthin the lag phase preceding benzyladenine-induced
      growth of cucumber cotyledons in the dark.
AB  - Changes in the rate of synthesis of cellular constituents were studied in
      detached cucumber cotyledons (Cucumis sativus L. cv. Ohio) after treatment with
      benzyladenine (BA). BA treatment stimulated RNA and DNA syntheses. The
      stimulation of RNA synthesis occurred within the lag phase preceding BA-induced
      growth, while that of DNA synthesis came during the growth. On the other hand,
      the stimulation by BA was not detected for protein and lipid syntheses. 5
      Fluorouracil (FU, 10(-3) m) plus thymidine (T, 10(-4) m) did not inhibit the
      fresh weight increase in both water- and BA-treated cotyledons, while alpha
      amanitin (AM, 10 ug/ml) inhibited it in both. AM added during the first 4 hr
      effectively inhibited the growth stimulation by BA, but AM added 6 hr or more
      after BA had almost no effect. FU+T strongly inhibited the incorporation of (3)H
      uridine into cytoplasmic ribosomal RNA (rRNA) and brought about labelling in
      regions other than those of the regular rRNA species on gel electrophoresis. On
      the other hand, AM had less influence on the synthesis of cytoplasmic rRNA than
      FU+T. These results indicate that BA stimulates cotyledon growth in the dark
      through its effect on messenger RNA synthesis within the lag phase of growth and
      the synthesis of cytoplasmic rRNA is not always necessary for cotyledon growth. 

PMID- 25385959
TI  - Reduction of plastocyanin with O2- and superoxide dismutase-dependent oxidation
      of plastocyanin by H2O2.
AB  - Type I copper proteins, plastocyanin and rice blue protein, were reduced with O2
      (-). The reduction rate constants of plastocyanins from several sources with O2 (
      ) are about 10(6) m(-1) sec(-1) (1.0 * 10(6) m(-1) sec(-1) for spinach and kidney
      bean plastocyanins and 6.7 * 10(5) m(-1)sec(-1) for Japanese radish plastocyanin)
      at pH 7.8 at 25 degrees C and not significantly different from that observed for
      rice blue protein (7.3 * 10(5) m(-1)sec(-1)). Reduced plastocyanin was oxidized
      by H2O2 through the peroxidase-like reaction of Cu,Zn-superoxide dismutase. 

PMID- 25385960
TI  - Physiological effects of cotyledons on gibberellin-induced cucumber hypocotyl
      elongation.
AB  - The cotyledon requirement for gibberellin-induced hypocotyl elongation of light
      grown cucumber (Cucumis sativus L. cv. Aonaga-jibae) seedlings was studied.
      Gibberellin A7 was used. At the saturation dosage, gibberellin-induced elongation
      was roughly proportional to the amount of the cotyledon retained. The cotyledon
      dependence of gibberellin-induced elongation was most marked when decotylization
      was done at the time of gibberellin treatment or at 24 hr after it. However, when
      the time of decotylization was delayed by more than 24 hr after gibberellin
      treatment, the effect was not immediate, and gibberellin-induced elongation
      continued for a while at a higher rate than that of the control. Young hypocotyls
      were more sensitive to gibberellin than older hypocotyls and their cotyledon
      requirement for gibberellin-induced elongation was less. Covering the cotyledons
      with aluminum foil or treating them with N'-(3,4-dichlorophenyl)-N-methoxy-N
      methylurea, a photosynthetic inhibitor, reduced the gibberellin effect. There was
      a quantitative relationship between the magnitude of the covered or the inhibitor
      treated area of the cotyledon and gibberellin-induced elongation. This
      quantitative relationship paralleled that for decotylization. These results
      suggested that the cotyledon requirement of the hypocotyl for gibberellin-induced
      elongation is at least partly related to the photosynthetic activity of the
      cotyledons. 

PMID- 25385961
TI  - Purification and characterization of acid phosphatase in aleurone particles of
      rice grains.
AB  - The major acid phosphatase (EC 3.1.3.2) associated with aleurone particles of
      rice grains (Oryza sativa L. Japonica cv. Koshihikari) was purified to
      homogeneous state by polyacrylamide gel electrophoresis. Its molecular weight was
      72,000 when determined by gel filtration and 68,000 when found by polyacrylamide
      gradient gel electrophoresis in the presence of sodium dodecyl sulfate and beta
      mercaptoethanol. The purified enzyme had a violet color and an absorption peak at
      530 nm. Triton X-100 and lysolecithin stabilized the purified enzyme. The optimum
      pH for hydrolysis of p-nitrophenyl phosphate was 4.8. The enzyme hydrolyzed all
      inositol phosphates, several other phosphomonoesters and pyrophosphate. However,
      alpha,beta-glycerol phosphate, glucose-6-phosphate, adenosine monophosphate and
      inosine monophosphate were not hydrolyzed. The Km for myo-inositol hexaphosphate
      was 0.43 mm, which was the lowest among myo-inositol phosphates. The Km value
      increased as the number of phosphate linkages on myo-inositol decreased. No
      correlation between the maximum initial velocity (Vmax) and Km was observed.
      Among the myo-inositol phosphates, the Vmax for myo-inositol triphosphate was the
      highest. The Km for p-nitrophenyl phosphate was 1.74 mm and that for ATP was 5.26
      mm. l-Tartrate, orthophosphate, molybdate and arsenate were competitive
      inhibitors, and F(-) was a noncompetitive inhibitor. Ag(+), Zn(2+), Hg(2+),
      Cu(2+) and Fe(2+) were inhibitory and the enzyme was also inactivated by
      preincubation with EDTA. 

PMID- 25385962
TI  - Isolation and characterization of NADH-glutamate synthase from pea (Pisum sativum
      L.).
AB  - Both ferredoxin-glutamate synthase (EC 1.4.7.1) and NADH-glutamate synthase (EC
      1.4.1.14) were isolated separately on DEAE-cellulose chromatography from
      etiolated pea shoots. The latter enzyme was purified 1,400-fold by ammonium
      sulfate fractionation and column chromatographies of DEAE-cellulose, Sephadex G
      200 and blue-Sepharose. The enzyme had a molecular weight of 220,000 and an
      isoelectric point of 4.3. The optimum pH was 7.6. Apparent Km values for l
      glutamine, 2-oxoglutarate and NADH were 400, 37 and 4 um, respectively. The
      enzyme had its absorption maxima at 275, 375 and 440 nm, suggesting that pea NADH
      glutamate synthase is a flavoprotein. It showed NADH-diaphorase activity toward
      ferricyanide and 2,6-dichlorophenol indophenol as the electron acceptor.
      Sulfhydryl reagents, metal-chelating reagents, phthalein acids and azaserine were
      strong inhibitors. Ammonium and phosphate ions enhanced the enzyme activity. 

PMID- 25385963
TI  - Inorganic pyrophosphatase from pollen of Typha latifolia.
AB  - An inorganic pyrophosphatase was purified about 3,800-fold from the pollen of
      Typha latifolia by chromatography on DEAE-Sephadex A-50, isoelectric focusing and
      gel filtration through Sephadex G-75. The enzyme had an optimum pH between 8.5
      9.5 and required Mg(2+). Since an excess of pyrophosphate over Mg(2+) inhibited
      the pyrophosphatase reaction, the actual substrate may have been an Mg
      pyrophosphate complex. The enzyme degraded inorganic pyrophosphate specifically,
      showing a Km value of 7.6 * 10(-5) m. A possible role of pyrophosphatase was
      discussed in connection with starch-sucrose conversion. 

PMID- 25385964
TI  - Photo-induced changes in proteins associated with floral induction in Amaranthus.
AB  - A. caudatus f. albiflorus, A. caudatus f. caudatus and A. tricolor var. tristis
      are qualitative SD plants with photo-inductive requirements of six, three and
      five, 8-hr photoperiodic cycles, respectively, for macroscopic inflorescence
      initiation. The total protein content gradually increased in both stem and leaves
      with an increasing number of inductive photoperiodic cycles. In both stem and
      leaves of all three plant types, two electrophoretically separable new water
      soluble protein bands appeared with completion of their respective photo
      inductive requirements for inflorescence initiation. In the stem of A. caudatus
      f. caudatus, a third band appeared after the plants had received only a single SD
      cycle. The new proteins formed concurrently with photoperiodic floral induction
      differed electrophoretically from plant to plant even though all plants used in
      the experiment were short-day plants and closely related taxonomically. 

PMID- 25385965
TI  - Studies on algal cytochromes II. Some physical and chemical properties of further
      purified Petalonia cytochrome c-553.
AB  - A cytochrome c-553 was isolated from a brown alga, Petalonia fascia, and its
      physical and chemical properties were investigated. At liquid nitrogen
      temperature, the alpha-, beta- and gamma-band of this cytochrome shifted 1-2 nm
      to the shorter wavelength in comparison with those at room temperature. The alpha
      band split into two peaks, 551.5 (major band) and 546.5 nm (minor band), at the
      low temperature. The cytochrome in high concentration showed a shoulder at 695 nm
      in its oxidized state, suggesting a methionine residue to be the sixth ligand of
      heme iron. The molecular weight was estimated to be about 10,000 containing one
      mole of heme c based on analyses of gel filtration, sodium dodecyl sulfate
      acrylamide gel electrophoresis, amino acid composition and iron content. The
      isoelectric points of the ferro- and ferricytochromes were estimated to be at pH
      4.1 and 4.3, respectively, by the isoelectric focusing method. The amino acid
      composition of this cytochrome was Lys6, Arg1, Asp15, Thr5, Ser6, Glu11, Pro2,
      Gly7, Ala7, Cys2, Val6, Met3, Ile6, Leu3, Tyr1, Phe3, Trp1, with a total of 86
      residues. The amino- and carboxylterminal sequences and four chymotryptic peptide
      sequences were compared with those of other cytochromes c to show that these
      cytochromes were homologous to one another. 

PMID- 25385966
TI  - Accumulation of sugars in cucumber leaves during calcium starvation.
AB  - To determine the metabolic role of calcium we grew cucumber plants without
      calcium. Symptoms of leaf injury such as chlorosis and marginal curling appeared
      a few days after the removal of calcium. The level of the soluble sugars in
      calcium deficient leaves increased to more than 10-fold that in the control at
      the late stage of treatment. In contrast, the level of the soluble sugars in the
      root decreased because of the calcium deficiency. The contents of soluble and
      bound calcium, in contrast to soluble sugars, decreased only in the young leaves
      of calcium deficient plants. The content of each soluble sugar measured by liquid
      chromatography was stable in the control leaves during treatment. Changes in
      sucrose, fructose, glucose, maltose and galactose in calcium deficient leaves
      were similar to the change in the total soluble sugars. The increases in
      stachyose and the mixture of raffinose and cellobiose took place only at the late
      stage of calcium starvation. The starch content in calcium deficient leaves was
      somewhat higher than that of the control, except for the remarkable decrease at
      the late stage. alpha-Amylase activities were not altered much in either the
      control or the calcium deficient plant during 5 days of treatment, but a clear
      increase took place at the late stage of calcium starvation. The reason for the
      distinct increase in the soluble sugars in calcium deficient leaves could be
      explained by the decline in transport due to the calcium deficiency. 

PMID- 25385967
TI  - Metabolism of indole-3-acetic acid and natural occurrence of dioxindole-3-acetic
      acid derivatives in Vicia roots.
AB  - Three indole-3-acetic acid (IAA) metabolites [compounds A and B and indole-3
      acetylaspartic acid (IAAsp) ] accumulated in Vicia faba roots when (14)C-IAA was
      applied to the cotyledon. IAAsp formation was increased by the application of a
      high concentration (2.5 * 10(-4) m) of IAA, while the accumulation of compound A
      was more conspicuous in the roots when a lower concentration (3.3 * 10(-5) m) of
      IAA had been applied. This indicates that compound A is not a detoxication
      product induced by an abnormally high concentration of IAA. Compounds A and B
      were identified as dioxindole-3-acetic acid derivatives by the UV spectra and
      their yielding 2-quinolone-4-carboxylic acid upon hydrolysis. Compound A was
      found to exist in Vicia roots not treated with exogenous IAA, and its naturally
      occurring content was estimated to be 1 MUmole kg(-1) fresh weight. The amount of
      native compound B was far less than that of compound A. 

PMID- 25385968
TI  - Direct demonstration of the involvement of chloroplasts in the rapid light
      induced potential change in tonoplast-free cells of Chara australis. Replacement
      of Chara chloroplasts with spinach chloroplasts.
AB  - To directly demonstrate the involvement of chloroplasts in the rapid light
      induced potential change we removed chloroplasts by centrifuging tonoplast-free
      cells of Chara australis. Chloroplast-free cells showed no signs of a potential
      change on illumination. When a chloroplast-free Chara cell was perfused with a
      suspension of chloroplasts isolated from other cells of Chara australis, it
      regained its ability to generate the rapid potential change induced by light.
      Chloroplasts were isolated from spinach leaves by a method which preserves the
      chloroplast envelope; thus ensuring the ability to assimilate CO2. When these
      chloroplasts were introduced into a transparent Chara cell containing no
      chloroplasts, normal rapid hyperpolarization was induced on illumination. When
      spinach chloroplasts were treated with a medium of very low osmotic potential, no
      O2 evolution was detected, but even with these chloroplasts rapid light-induced
      hyperpolarization was observed. We concluded that chloroplasts are essential for
      the rapid light-induced potential change and that chloroplasts can be replaced
      with those of another species, so far as the light-induced potential change is
      concerned. 

PMID- 25385969
TI  - Demonstration of the K+ channel in the plasmalemma of tonoplast-free cells of
      Chara australis.
AB  - Tonoplast-free and ATP-less internodal cells of Chara australis were made by
      perfusing cells internally with a medium containing ethyleneglycol-bis-(beta
      aminoethylether) N, N'-tetraacetic acid, hexokinase and glucose. Such a cell
      showed rapid light-induced potential change when it was stained with neutral red
      (5). The rapid light-induced potential change was inhibited by
      tetraethylammonium, a known inhibitor of the K(+) channel in nerve cells.
      Tetraethylammonium acted both from the inside of the membrane and from the
      outside with similar effectiveness. Nonyltriethylammonium inhibited the light
      response far more effectively than did tetraethylammonium. The results suggest
      the existence of a K(+) channel which is activated by light in the Chara
      membrane. 

PMID- 25385970
TI  - Effects of temperature on glycolate metabolism in Chlorella.
AB  - The effect of temperature on the products of photosynthetic carbon metabolism was
      studied in Chlorella vulgaris 11h cells which had been grown with air enriched
      with 2-3% CO2. During the test period, 300 ppm of (14)CO2 was used. On raising
      the temperature from 20 to 36 degrees C during photosynthetic (14)CO2 fixation,
      (14)CO2-incorporation into glycolate immediately stopped whereas that into
      sucrose was greatly enhanced. When the temperature was lowered from 36 to 20
      degrees C, (14)C-glycolate formation was greatly enhanced, but sucrose formation
      slowed. No significant change in the rate of total (14)CO2 fixation was induced
      by either temperature change. At 20 degrees C the radioactivity incorporated into
      glycolate was about 20% of the total (14)C fixed, but it decreased to less than
      2% at 32 degrees C. When alpha-hydroxy-2-pyridinemethane-sulfonate was added, the
      percent incorporation of (14)C into glycolate was enhanced to 30% at 20 degrees C
      as well as at 32 degrees C. The increase in (14)C-incorporation into glycolate
      was accompanied by a decrease in sucrose and glucose-polymer, although the total
      (14)CO2 fixation was not significantly affected by this inhibitor; most of the
      labelled glycolate appeared in the algal medium. 

PMID- 25385971
TI  - Interaction between antimycin and cytochrome b560 in Chromatium chromatophores
      The red shift of the absorption spectrum and photoreduction of cytochrome b560 in
      the presence of antimycin.
AB  - In the presence of dithionite, which reduced all the cytochromes present in
      Chromatium chromatophores, the addition of antimycin caused a shift (1-2 nm) of
      the alpha band in the absorption spectrum of reduced cytochrome b560 toward
      longer wavelength. The difference spectrum (antimycin-added-minus-no addition)
      had a trough at 556 nm, a peak at 564 nm and an isosbestic point at 561 nm. The
      locations of the trough, peak and isosbestic point did not depend on the
      concentration of antimycin, but the amount of shifted cytochrome b560 increased
      as the concentration of antimycin increased. As reported previously, a single
      turnover flash reduced cytochrome b560 in the presence of antimycin. The extent
      of the reduction depended on the concentration of antimycin. Both titrations of
      the red shift and the photoreduction of cytochrome b560 with antimycin fitted a
      first-order sigmoid curve with a half-maximum value at 5 * 10(-7) m of antimycin
      concentration. The results indicated that antimycin molecules interacted with, or
      were bound to, cytochrome b560 molecules in the ratio of one to one with an
      apparent dissociation constant of 3.5-7.3 * 10(-7) m. 

PMID- 25385972
TI  - Effects of ultraviolet irradiation on growth and pigmentation in seedlings.
AB  - Dark-germinated seedlings of maize, radish, soybean, cucumber and eggplant were
      grown for 2 or 3 days under ultraviolet light, and the differential effects of UV
      according to wavelength regions were evaluated. Although the effectiveness of UV
      irradiation differed somewhat depending on the plant species, generally, four
      wavelength regions having different effects were discerned. The region from 287
      to 302 nm was phytotoxic, causing bronzing (radish), epinasty and blazing
      (cotyledon, cucumber), formation of brown flecks (soybean), and also severe
      growth inhibition in hypocotyls. The region from 300 to 338 nm greatly promoted
      anthocyanin formation and inhibited the shoot elongation. The region from 330 to
      370 nm inhibited shoot elongation and promoted cotyledon growth as well as
      chlorophyll formation. The effects of the region from 384 to 400 nm were
      generally weak, but in maize coleoptile, radish and soybean hypocotyls this
      region exerted a distinct inhibition, stronger than the region of 330-370 nm, and
      in chlorophyll formation in maize coleoptile this region was the most effective
      of those tested. The above-stated shoot growth inhibition and anthocyanin
      formation caused by UV were generally greater than those caused by blue or red
      light, but growth promotion in the cotyledons was smaller. 

PMID- 25385973
TI  - Copper as a controlling factor of anaerobic growth under N2O and biosynthesis of
      N2O reductase in denitrifying bacteria.
AB  - In order to determine the specific mineral requirement for N2O-anaerobic growth
      of the denitrifying bacteria Alcaligenes sp. NGIB 11015 and Alcaligenes faecalis
      IAM 1015, investigations were done using dithizone-treated KNO3-free modified
      Giltay's medium (dithizone-treated medium). When grown aerobically, the bacteria
      exhibited equally good growth in the presence or absence of an appropriate amount
      of copper. Anaerobic growth under N2O was stimulated by the addition of a proper
      amount of copper in both denitrifying bacteria. Growth in the medium demetalated
      by various treatments showed that copper was specifically necessary for the
      maximum growth under N2O. The optimum concentration of copper was between 0.5 to
      1 MUm and 20 to 40 MUm for the anaerobic growth rate under N2O. Copper was
      indispensable for the biosynthesis of N2O reductase and is very likely to be a
      functional part of N2O reductase in denitrifying bacteria. 

PMID- 25385974
TI  - Ultraviolet absorption spectrum change induced by the interaction between
      chloroplast coupling factor 1 and ADP or ATP.
AB  - Changes in the ultraviolet absorption spectrum took place when coupling factor 1
      of spinach chloroplasts (CF1) was mixed with ATP or ADP. The difference spectrum
      had a maximum at about 278 nm and a minimum at about 250 nm. The profile of the
      difference spectrum inidcates a shift in the absorption spectrum of the ADP or
      ATP bound to CF1. The ratio of the maximal absorbance change at about 278 nm to
      the absorbance of CF1 at that wavelength was 0.027-0.048. The molar concentration
      of nucleotide required to give the maximal absorbance change was 2-3 times that
      of CF1 when Ca(2-) or Mg(2+) was present. AMP induced no significant spectral
      change. When ADP was added, the absorbance change reached a plateau within a few
      minutes if Mg(2-) or Ca(2+) was present. The absorbance change induced by ATP
      reached a plateau within a few minutes only when Ca(2+) was present. In the
      presence of Mg(2+), it reached a plateau of nearly the same level, but at a
      slower rate. The absorbance change was reduced in the presence of EDTA. PPi
      effectively inhibited the absorbance change induced by ADP and Mg(2+). 

PMID- 25385975
TI  - Glycerolipid synthesis in Avena leaves during greening of etiolated seedlings I.
      Lipid changes in leaves.
AB  - Etiolated seedlings of Avena sativa L. were illuminated under fluorescent light
      of 1,500 lux at 25 degrees C and the lipid changes in their first leaves and
      isolated plastids were followed during 24 hr of greening. Lipid changes were
      divided into a degradation phase [0 hr of illumination (hr-L) to 3 hr-L] and a
      synthetic phase (3 hr-L to 24 hr-L). In the degradation phase, which paralleled
      prolamellar body transformation in the plastids, both plastidic lipids,
      monogalactosyldiglyceride (MGDG), digalactosyldiglyceride (DGDG),
      sulfoquinovosyldiglyceride (SQDG) and phosphatidylglycerol (PG), and
      extraplastidic lipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE)
      and phosphatidylinositol (PI), were partially degraded. Plastidic lipids (except
      DGDG) began to increase at 1.5 hr-L without the de novo synthesis of fatty acids,
      at the same time that there was a temporary accumulation of diglyceride, whose
      fatty acids were similar to the fatty acids of phospholipids such as PC, PE and
      PI, but different from the fatty acids of DGDG. This suggests that there is
      conversion of phospholipids to plastidic lipids during the later degradation
      phase. During the later degradation phase and the early synthetic phase (until 6
      hr-L), plastid division occurred, resulting in a 30% increase in the plastid
      number per cell. Plastidic lipids were synthesized rapidly during the synthetic
      phase, in accordance with the beginning of light-enhanced fatty acid synthesis
      and thylakoid proliferation. In addition, the fatty acid composition of the
      plastidic lipids changed markedly throughout the synthetic phase : in MGDG, DGDG
      and SQDG, alpha-linolenate increased as linoleate decreased at both the C-1 and C
      2 positions of sn-glycerol; in PG, alpha-linolenate increased in compensation for
      the decrease in linoleate at C-1 and hexadecenoate (3t) appeared and increased in
      compensation for the decrease in palmitate at C-2. This is evidence of the
      parallel desaturation of linoleate to linolenate at both C-1 and C-2 of MGDG,
      DGDG and SQDG, and also of the position-specific desaturation of linoleate to
      linolenate at C-1 of PG and of palmitate to hexadecenoate at C-2 of PG. The
      formation of hexadecenoate was entirely light-dependent. Extraplastidic lipids
      increased slightly in the early synthetic phase (3 hr-L to 6 hr-L), but declined
      later. 

PMID- 25385976
TI  - Glycerolipid synthesis in Avena leaves during greening of etiolated seedlings II.
      alpha-Linolenic acid synthesis.
AB  - To determine the synthesis of alpha-linolenic acid esterified to galactolipids,
      etiolated leaves from Avena sativa L. were fed with [1-(14)C]acetate for the
      first 3 hr of greening, and the redistribution of (14)C incorporated into the
      fatty acid moieties of lipid classes was examined during a 21-hr chase.
      Phosphatidylcholine (PC) was most heavily labeled, but lost a large portion of
      its (14)C during the chase. Galactolipids, such as monogalactosyl-diglyceride
      (MGDG) and digalactosyldiglyceride (DGDG), were only slightly labeled at the
      start, but gradually gained (14)C during the chase. When greening Avena leaves
      were pulse-labeled with [2-(3)H]glycerol and chased in the same manner, a similar
      incorporation and redistribution of (3)H were observed in the glycerol moieties
      of lipid classes. A [1-(14)C]oleic acid-feeding experiment also showed the same
      redistribution of (14)C from PC to galactolipids and little change of the (14)C
      incorporated into phosphatidylglycerol and phosphatidylethanolamine. These
      results are evidence that galactolipids were synthesized from PC in greening
      Avena leaves. Time courses for the (14)C in the fatty acid moieties of lipid
      classes in both [1-(14)C]-acetate- and [1-(14)C] oleic acid-feeding experiments
      showed dominant labeling of oleoyl-PG during the early hours and the subsequent
      transfer of the label from oleoyl-PG to linoleoyl-PC, linoleoyl-MGDG and finally
      to alpha-linolenoyl-MGDG. From these results, the major pathway of alpha
      linolenic acid synthesis in greening Avena leaves is proposed: oleate synthesized
      de novo is first acylated to PG then desaturated to linoleoyl-PC, which is in
      turn converted to MGDG and desaturated to alpha-linolenoyl-MGDG. Because of the
      slow incorporation of (14)C into alpha-linolenoyl-DGDG, in contrast to the rapid
      incorporation of (14)C into a-linolenoyl-MGDG, in the [1-(14)C] acetate- and [1
      (14)C]linoleic acid-feeding experiments, the former lipid class seems to be
      formed by the galactosylation of the latter rather than by the desaturation of
      linoleoyl-DGDG. The involvement of PC-exchange protein in the transfer of
      linoleoyl-PC from ER to the plastid is discussed. 

PMID- 25385977
TI  - Phototransformation of the red-light-absorbing form of undegraded pea phytochrome
      by laser flash excitation.
AB  - The phototransformation of undegraded pea phytochrome, which was estimated to be
      about 30 to 40% pure, from its red-light-absorbing form to its far-red-light
      absorbing form was examined at 2-4 degrees C after laser flash excitation at 655
      nm using a custom-designed multichannel transient spactra analyzer. A difference
      spectrum measured 10 MUsec after the flash showed an absorbance increase at 692
      nm, a decrease at 660 nm and a slight decrease at 604 nm. With time in darkness,
      the peak at 692 nm gradually decreased in magnitude and shifted to 695 nm. A
      decay curve of absorbance at 692 nm between 10 and 500 MUsec after the flash
      could be resolved into two reaction components, one proceeding with a rate
      constant of 46,000 sec(-1) and the other with one of 2,500 sec(-1). The faster
      component has not been reported previously. Difference spectra also indicated
      that a small but significant increase in absorbance between 400 and 410 nm and
      decrease around 360 nm took place 10-260 MUsec after the flash. 

PMID- 25385978
TI  - Changes revealed by a tracer technique in the amino acid metabolism of
      thermodormant and non-dormant New York lettuce seeds.
AB  - The metabolism of glycerol-(14)C(U) in non-thermodormant New York lettuce seeds
      was compared with that in thermodormant ones in order to find metabolic changes
      and a possible osmotic substance(s) in the non-dormant seeds. The higher
      incorporation of radioactivity into cationic substances in the non-dormant seeds
      revealed rapid synthesis and large pool sizes for some amino acids, especially
      Gln and Glu, before radicle protrusion. The enormous accumulation of Gln and Glu
      in germinating seeds indicates that these amino acids may act as osmotic
      substances in the germination of New York lettuce seeds. There were no
      indications that an osmotic substance(s) is included in the neutral and acidic
      fractions of the 80%-ethanol extracts. Time course analyses of free amino acids
      showed changes in the metabolism of free amino acids, especially Arg and Asn, at
      the early stage (4 to 8 hr) of imbibition both in thermodormant and in non
      dormant seeds. These data are evidence that the metabolism of amino acids in New
      York lettuce seeds was affected by temperature treatment from the early stage of
      imbibition. 

PMID- 25385979
TI  - Accumulation of free amino acids in the tips of non-thermodormant embryonic axes
      accounts for the increase in the growth potential of New York lettuce seeds.
AB  - Accumulation of free amino acids took place only in growing axes during the first
      24 hr of imbibition at 18 degrees C. A ninhydrin-positive section was shown to be
      located at the tips of the axes by a histochemical technique. The amount of free
      amino acids accumulated just at the breaking of the seed coats in the non-dormant
      axes was great enough to account for the increase in the growth potential, i.e.,
      the force to rupture the testa. About 72% of the accumulated free amino acids in
      the non-thermodormant embryonic axes was comprised of glutamine and glutamate. 

PMID- 25385980
TI  - Effects of temperature, red light and hormones on the accumulation of free amino
      acids in osmotically growth-inhibited embryonic axes of New York lettuce seeds.
AB  - Free amino acids accumulated in non-thermodormant embryonic axes of New York
      lettuce seeds from the 16th to the 24th hour of imbibition, even when germination
      was prevented with 0.3 m mannitol. The accumulation of free amino acids in the
      embryonic axes was affected by temperature, red light and hormones (gibberellic
      acid, kinetin and abscisic acid), and was correlated with the growth potential of
      the axes. These data are evidence that the accumulation of free amino acids in
      the embryonic axes is not the result of axes-growth, but one of its causes. 

PMID- 25385981
TI  - Phytochrome-mediated accumulation of free amino acids in embryonic axes of New
      York lettuce seeds.
AB  - Red light given to New York lettuce seeds incubated on a 0.3 m mannitol solution
      increased the amount of free amino acids in the embryonic axes, far-red light
      reversed this effect. Germination in response to red light given at various times
      during imbibition was closely related to the amount of free amino acids
      accumulated in the axes in response to the red light. The analyses of the free
      amino acids that accumulated in the axes of seeds incubated on 0.3 m mannitol
      indicated that the free amino acids that accumulated on red-light irradiation
      were produced by the degradation of storage protein. This is evidence that red
      light-increased germination may be caused by the accumulation of free amino acids
      in the embryonic axes of New York lettuce seeds. 

PMID- 25385982
TI  - The effect of acetylcholine on hypocotyl elongation in soybean.
AB  - Acetylcholine (Ach) and gibberellic acid (GA3) treatment of germinating seeds
      stimulated hypocotyl elongation in the soybean cultivar Otootan. Ethrel which
      evolves ethylene in plant tissues, markedly inhibited hypocotyl elongation.
      Ethrel also inhibited the Ach- and GA3-induced stimulation of hypocotyl
      elongation. The effects of Ach and GA3 were not additive. 

PMID- 25385983
TI  - Effect of low water potential of the culture medium on mesocotyl elongation of
      rice seedlings.
AB  - At a soil water content of water potential of ca. -3.1 to -6.2 bars, mesocotyl
      elongation of both indica and japonica type rice was extremely stimulated. It was
      also stimulated in an aseptic culture medium (2.5-4.0% mannitol, water potential
      ca. -3.5 to -5.5 bars). The stimulation of the mesocotyl may be caused by cell
      multiplication. 

PMID- 25385984
TI  - Stimulation of light-induced lipid peroxidation by salts in isolated chloroplasts
      in the presence of carbonylcyanide m-chlorophenylhydrazone.
AB  - Effects of salts on light-induced lipid peroxidation were examined in isolated
      spinach chloroplasts. In the presence of carbonylcyanide m-chlorophenylhydrazone,
      salts stimulated lipid peroxidation, which was partially suppressed by superoxide
      dismutase. Salts may cause the stimulation by decreasing the negative surface
      charges on the thylakoid membrane, in addition to affecting electron transport. 

PMID- 25385985
TI  - Preliminary characterization of a cholinesterase from roots of Bengal gram -
      Cicer arietinum L.
AB  - A Cholinesterase was isolated and purified (65-fold) from roots of Bengal gram
      (Cicer arietinum L.) seedlings. It hydrolyzes acetylcholine and acetylthiocholine
      more readily than propionylthiocholine or butyrylthiocholine. The enzyme has high
      affinity for acetylthiocholine (Km=150 MUm) and is inhibited by animal
      anticholinesterases, neostigmine and physostigmine, and by Phosfon-D, a plant
      growth retardant. 

PMID- 25385986
TI  - Further characterization of Nostoc verrucosum ferredoxins.
AB  - Nostoc verrucosum ferredoxins Fd I and Fd II were found to have different amino
      acid compositions. Fd I had 98 amino acid residues of Trpo, Lys4, His1, Arg1,
      Asp14, Thr8, Ser6, Glu14, Pro4, Gly7, Ala10, Cys4, Val5, Met0, Ile6, Leu8, Tyr5,
      Phe1 while Fd II had 99 residues of Trp1, Lys4, His1, Arg1, Asp18, Thr7, Ser6,
      Glu14, Pros, Gly5, Ala6, Gys5, Val6, Met1, Ile6, Leu8, Tyr4,Phe1. From the amino
      acid compositions, molecular weights were calculated to be about 10,500 for Fd I
      and 10,700 for Fd II. The amino terminals of both Fd I and Fd II were alanine.
      The carboxyl terminal sequence of Fd I was -Glu-Leu-Tyr and that of Fd II was 
      Glu-(Ser, Ala)-Leu-Ala. Fd I was more resistant against heat denaturation than Fd
      II. 

PMID- 25385988
TI  - Rhizobium alvei sp. nov., isolated from a freshwater river.
AB  - A bacterial strain designated TNR-22(T) was isolated from a freshwater river in
      Taiwan and characterized using a polyphasic taxonomic approach. Cells of strain
      TNR-22(T) were facultatively anaerobic, Gram-stain-negative, rod-shaped, motile
      by a single polar flagellum and formed cream-coloured colonies. Growth occurred
      at 4-45  degrees C (optimum, 25-30  degrees C), with 0-1.0 % (w/v) NaCl (optimum,
      0.5 %) and at pH 7.0-8.0 (optimum, pH 7.0). Strain TNR-22(T) did not form nodules
      on Macroptilium atropurpureum. The nifH gene encoding denitrogenase reductase was
      not detected by PCR. The major fatty acids (>10 %) of strain TNR-22(T) were C18 :
      1omega7c and C16 : 0. The DNA G+C content was 60.3 mol%. The polar lipid profile
      consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol,
      phosphatidylcholine, diphosphatidylglycerol, an uncharacterized aminoglycolipid
      and an uncharacterized phospholipid. Comparative analysis of 16S rRNA gene
      sequences showed that strain TNR-22(T) constituted a distinct branch within the
      genus Rhizobium, showing the highest level of sequence similarity with Rhizobium
      rosettiformans W3(T) (96.3 %). Phenotypic characteristics of the novel strain
      also differed from those of the most closely related species of the genus
      Rhizobium. On the basis of the genotypic, chemotaxonomic and phenotypic data,
      strain TNR-22(T) represents a novel species in the genus Rhizobium, for which the
      name Rhizobium alvei sp. nov. is proposed. The type strain is TNR-22(T) ( = BCRC
      80408(T) = LMG 26895(T) = KCTC 23919(T)).

PMID- 25385989
TI  - Rhizobium sophorae sp. nov. and Rhizobium sophoriradicis sp. nov., nitrogen
      fixing rhizobial symbionts of the medicinal legume Sophora flavescens.
AB  - Five bacterial strains representing 45 isolates originated from root nodules of
      the medicinal legume Sophora flavescens were defined as two novel groups in the
      genus Rhizobium based on their phylogenetic relationships estimated from 16S rRNA
      genes and the housekeeping genes recA, glnII and atpD. These groups were
      distantly related to Rhizobium leguminosarum USDA 2370(T) (95.6 % similarity for
      group I) and Rhizobium phaseoli ATCC 14482(T) (93.4 % similarity for group II) in
      multilocus sequence analysis. In DNA-DNA hybridization experiments, the reference
      strains CCBAU 03386(T) (group I) and CCBAU 03470(T) (group II) showed levels of
      relatedness of 17.9-57.8 and 11.0-42.9 %, respectively, with the type strains of
      related species. Both strains CCBAU 03386(T) and CCBAU 03470(T) contained
      ubiquinone 10 (Q-10) as the major respiratory quinone and possessed 16 : 0, 18 :
      0, 19 : 0 cyclo omega8c, summed feature 8 and summed feature 2 as major fatty
      acids, but did not contain 20 : 3 omega6,8,12c. Phenotypic features
      distinguishing both groups from all closely related species of the genus
      Rhizobium were found. Therefore, two novel species, Rhizobium sophorae sp. nov.
      for group I (type strain CCBAU 03386(T) = E5(T) = LMG 27901(T) = HAMBI 3615(T))
      and Rhizobium sophoriradicis sp. nov. for group II (type strain CCBAU 03470(T) =
      C-5-1(T) = LMG 27898(T) = HAMBI 3510(T)), are proposed. Both groups were able to
      nodulate Phaseolus vulgaris and their hosts of origin (Sophora flavescens)
      effectively and their nodulation gene nodC was phylogenetically located in the
      symbiovar phaseoli.

PMID- 25385990
TI  - Pseudomonas yamanorum sp. nov., a psychrotolerant bacterium isolated from a
      subantarctic environment.
AB  - A psychrotolerant strain, 8H1(T), was isolated from soil samples collected in
      Isla de los Estados, Ushuaia, Argentina. Cells were Gram-negative, aerobic,
      straight rods, occurring singly or in pairs, non-spore-forming and motile by
      means of two polar flagella. The isolate was able to grow in the range 4-35 
      degrees C, with optimum growth at 28  degrees C. The predominant cellular fatty
      acids were summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c), C16 : 0 and
      summed feature 8 (C18 : 1omega6c and/or C18 : 1omega7c). The polar lipid pattern
      of strain 8H1(T) comprised phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine and an unknown phospholipid. Ubiquinone 9 (Q-9) was the
      predominant lipoquinone. The DNA G+C content was 59.8 mol%. 16S rRNA gene
      sequence-based phylogeny suggested the affiliation of strain 8H1(T) to the
      'Pseudomonas fluorescens group', displaying >=98.5 % sequence similarity to 29
      type strains. A multilocus sequence analysis (MLSA) study performed by
      concatenating 16S rRNA, gyrB, rpoD and rpoB gene sequences showed that isolate
      8H1(T) could be discriminated from closely related species of the genus
      Pseudomonas and placed in the 'Pseudomonas gessardii subgroup', including the
      species with the highest MLSA sequence similarities: Pseudomonas brenneri (96.2
      %), P. gessardii (96.1 %), P. proteolytica (96.0 %), P. meridiana (96.0 %) and P.
      mucidolens (95.4 %). DNA-DNA hybridization analysis between 8H1(T) and the type
      strains of these closely related species revealed relatedness values of 27.0,
      8.8, 41.2, 39.7 and 46.1 %, respectively. These results, together with
      differences in several phenotypic features, support the classification of a novel
      species, for which the name Pseudomonas yamanorum sp. nov. is proposed. The type
      strain is 8H1(T) ( = DSM 26522(T) = CCUG 63249(T) = LMG 27247(T)).

PMID- 25385991
TI  - Sphingobium subterraneum sp. nov., isolated from ground water.
AB  - A Gram-stain-negative, strictly aerobic, non-motile, non-spore-forming, yellow,
      rod-shaped bacterium, designated S-II-13(T), was isolated from ground water at
      Daejeon in Korea. Strain S-II-13(T) grew between 15 and 30  degrees C (optimal
      growth at 28  degrees C), between pH 6.0 and 9.0 (optimal growth at pH 7.5) and
      at salinities of 0.3-1.5 % (w/v) NaCl, growing optimally with 0.5 % (w/v) NaCl.
      On the basis of 16S rRNA gene sequence analysis, strain S-II-13(T) was found to
      belong to the genus Sphingobium, showing closest phylogenetic similarity to
      Rhizorhapis suberifaciens CA1(T) (97.0 % 16S rRNA gene sequence similarity),
      Sphingobium sufflavum HL-25(T) (96.9 %) and Sphingobium vulgare HU1-GD12(T) (96.6
      %). The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine
      and sphingoglycolipid. The predominant ubiquinone was Q-10. The major fatty acids
      were C18 : 1omega7c, C14 : 0 2-OH, C16 : 0 and summed feature 3 (C16 : 1omega7c
      and/or iso-C15 : 0 2-OH). The DNA G+C content of strain S-II-13(T) was 63.5 mol%.
      DNA-DNA relatedness between strain S-II-13(T) and Rhizorhapis suberifaciens LMG
      17323(T), Sphingobium sufflavum KCTC 23953(T) and Sphingobium vulgare KCTC
      22289(T) was 24, 52 and 55 %, respectively. On the basis of evidence from this
      taxonomic study using a polyphasic approach, strain S-II-13(T) represents a novel
      species of the genus Sphingobium for which the name Sphingobium subterraneum sp.
      nov. is proposed. The type strain is S-II-13(T) ( = KACC 17606(T) = NBRC
      109814(T)).

PMID- 25385992
TI  - Rhodococcus aerolatus sp. nov., isolated from subarctic rainwater.
AB  - A Gram-stain-positive, rod-shaped and non-motile strain, designated PAMC
      27367(T), was isolated from rainwater collected on the Bering Sea. Analysis of
      the 16S rRNA gene sequence of the strain showed an affiliation with the genus
      Rhodococcus. Phylogenetic analyses revealed that strain PAMC 27367(T) formed a
      robust clade with the type strains of Rhodococcus rhodnii, Rhodococcus
      aetherivorans and Rhodococcus ruber with 16S rRNA gene sequence similarities of
      96.3 %, 95.8 % and 95.5 %, respectively. Cells of the strain grew optimally at 25
      degrees C and at pH 6.5-7.0 in the presence of 0-2 % (w/v) sea salts. The major
      polar lipids were diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside
      and three unknown phospholipids. The major cellular fatty acids (>10 %) were iso
      C16 : 0, C17 : 1omega8c and 10-methyl C17 : 0. Cell wall analysis showed that
      strain PAMC 27367(T) contained meso-diaminopimelic acid. The genomic DNA G+C
      content was 77.1 mol%. Based on the phylogenetic, chemotaxonomic and phenotypic
      data presented here, we propose a novel species with the name Rhodococcus
      aerolatus sp. nov., with PAMC 27367(T) ( = KCTC 29240(T) = JCM 19485(T)) as the
      type strain.

PMID- 25385993
TI  - Brenneria populi sp. nov., isolated from symptomatic bark of Populus*euramericana
      canker.
AB  - Five Gran-stain-negative, facultatively anaerobic, motile, bacterial strains were
      isolated from symptomatic bark tissue of Populus*euramericana canker. Strains
      grew at 4-41  degrees C, pH 4-10 and 0-6 % (w/v) salinity. They were positive
      with respect to catalase activity and negative for oxidase activity, nitrate
      reduction and the Voges-Proskauer reaction. Analysis of 16S rRNA gene sequences
      indicated that these five poplar isolates belong to the genus Brenneria, having
      highest sequence similarity of 95.98 % with Brenneria goodwinii LMG 26270(T).
      These five isolates formed a single cluster based on multilocus sequence
      analysis, indicating that they all belong to a single taxon within the genus
      Brenneria, which was confirmed by DNA-DNA hybridization. The DNA G+C content was
      54.9-55.7 mol%, and the main fatty acids were C16 : 0, C18 : 1omega7c, C17 : 0
      cyclo and C16 : 1omega7c/iso-C15 : 0 2-OH. Based on these results, we describe a
      novel species of the genus Brenneria with the proposed name Brenneria populi sp.
      nov. The type strain is D9-5(T) ( = CFCC 11963(T) = KCTC 42088(T)).

PMID- 25385994
TI  - Belliella kenyensis sp. nov., isolated from an alkaline lake.
AB  - A red-pigmented, Gram-reaction-negative, aerobic bacterial strain, designated
      No.164(T), was isolated from sediment sample from the alkaline Lake Elmenteita
      located in the Kenyan Rift Valley. Results of 16S rRNA gene sequence analysis
      indicated that the isolate represented a member of the genus Belliella, with the
      highest sequence similarity (97 %) to Belliella pelovolcani DSM 46698(T). Optimal
      growth temperature was 30-35  degrees C, at pH 7.0-12.0 in the presence of 0-4 %
      (w/v) NaCl. Flexirubins were absent. The respiratory menaquinone (MK-7),
      predominant cellular fatty acids (iso-C15 : 0, anteiso-C15 : 0 and a mixture of
      C16 : 1omega7c and/or iso-C15 : 0 2-OH) and DNA G+C content (38.1 mol%) of strain
      No.164(T) were consistent with those of other members of the genus Belliella. The
      polar lipids consisted of phosphatidylethanolamine, eight unspecified lipids and
      one unspecified phospholipid. Several phenotypic characteristics can be used to
      differentiate this isolate from those of other species of the genus Belliella.
      The results of polyphasic analyses presented in this study indicated that this
      isolate should be classified as representing a novel species of the genus
      Belliella. The name Belliella kenyensis sp. nov. is therefore proposed; the type
      strain is strain No.164(T) ( = DSM 46651(T) = CECT 8551(T)).

PMID- 25385995
TI  - Reappraisal of the taxonomy of Streptococcus suis serotypes 20, 22 and 26:
      Streptococcus parasuis sp. nov.
AB  - In order to clarify the taxonomic position of serotypes 20, 22 and 26 of
      Streptococcus suis, biochemical and molecular genetic studies were performed on
      isolates (SUT-7, SUT-286(T), SUT-319, SUT-328 and SUT-380) reacted with specific
      antisera of serotypes 20, 22 or 26 from the saliva of healthy pigs as well as
      reference strains of serotypes 20, 22 and 26. Comparative recN gene sequencing
      showed high genetic relatedness among our isolates, but marked differences from
      the type strain S. suis NCTC 10234(T), i.e. 74.8-75.7 % sequence similarity. The
      genomic relatedness between the isolates and other strains of species of the
      genus Streptococcus, including S. suis, was calculated using the average
      nucleotide identity values of whole genome sequences, which indicated that
      serotypes 20, 22 and 26 should be removed taxonomically from S. suis and treated
      as a novel genomic species. Comparative sequence analysis revealed 99.0-100 %
      sequence similarities for the 16S rRNA genes between the reference strains of
      serotypes 20, 22 and 26, and our isolates. Isolate STU-286(T) had relatively high
      16S rRNA gene sequence similarity with S. suis NCTC 10234(T) (98.8 %). SUT-286(T)
      could be distinguished from S. suis and other closely related species of the
      genus Streptococcus using biochemical tests. Due to its phylogenetic and
      phenotypic similarities to S. suis we propose naming the novel species
      Streptococcus parasuis sp. nov., with SUT-286(T) ( = JCM 30273(T) = DSM 29126(T))
      as the type strain.

PMID- 25385996
TI  - Description of Kribbella italica sp. nov., isolated from a Roman catacomb.
AB  - A novel actinobacterium, strain BC637(T), was isolated from a biodeteriogenic
      biofilm sample collected in 2009 in the Saint Callixstus Roman catacomb. The
      strain was found to belong to the genus Kribbella by analysis of the 16S rRNA
      gene. Phylogenetic analysis using the 16S rRNA gene and the gyrB, rpoB, relA,
      recA and atpD concatenated gene sequences showed that strain BC637(T) was most
      closely related to the type strains of Kribbella lupini and Kribbella
      endophytica. DNA-DNA hybridization experiments confirmed that strain BC637(T) is
      a genomic species that is distinct from its closest phylogenetic relatives, K.
      endophytica DSM 23718(T) (63 % DNA relatedness) and K. lupini LU14(T) (63 % DNA
      relatedness). Physiological comparisons showed that strain BC637(T) is
      phenotypically distinct from the type strains of K. endophytica and K. lupini.
      Thus, strain BC637(T) represents the type strain of a novel species, for which
      the name Kribella italica sp. nov. is proposed ( = DSM 28967(T) = NRRL B
      59155(T)).

PMID- 25386000
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of Mollicutes: minutes of the meetings (closed and open), 1 and 5 June
      2014, Blumenau SC, Brazil.

PMID- 25385997
TI  - Proposal of Thorsellia kenyensis sp. nov. and Thorsellia kandunguensis sp. nov.,
      isolated from larvae of Anopheles arabiensis, as members of the family
      Thorselliaceae fam. nov.
AB  - Two Gram-negative, rod-shaped strains, T2.1(T) and W5.1.1(T), isolated from
      larvae of the mosquito Anopheles arabiensis, were investigated using a polyphasic
      approach. On the basis of 16S rRNA gene sequence similarity studies, strains
      T2.1(T) and W5.1.1(T) were shown to belong to the genus Thorsellia, both showing
      97.8 % similarity to the type strain of Thorsellia anophelis, with 98.1 %
      similarity to each other. Chemotaxonomic data supported the allocation of the
      strains to the genus Thorsellia: their major fatty acids were C18 : 1omega7c, C16
      : 0 and C14 : 0 and they harboured a ubiquinone Q-8 quinone system and a
      polyamine pattern with the major compound 1,3-diaminopropane. Qualitative and
      quantitative differences in their polar lipid profiles distinguished strains
      T2.1(T) and W5.1.1(T) from each other and from T. anophelis. Average nucleotide
      identity (ANI), DNA-DNA hybridization, multilocus sequence analysis (MLSA) as
      well as physiological and biochemical tests allowed T2.1(T) and W5.1.1(T) to be
      distinguished both genotypically and phenotypically from each other and from the
      type strain of T. anophelis. Thus, we propose that these isolates represent two
      novel species of the genus Thorsellia, named Thorsellia kenyensis sp. nov. (type
      strain T2.1(T) = CCM 8545(T) = LMG 28483(T) = CIP 110829(T)) and Thorsellia
      kandunguensis sp. nov. (type strain W5.1.1(T) = LMG 28213(T) = CIP 110794(T)).
      Furthermore, phylogenetic analysis based on nearly full-length 16S rRNA gene
      sequences showed that the genus Thorsellia forms a separate branch, distinct from
      the families Enterobacteriaceae, Pasteurellaceae and Orbaceae. As a consequence,
      a new family Thorselliaceae fam. nov. is proposed. An emended description of
      Thorsellia anophelis is also provided.

PMID- 25386001
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of phototrophic bacteria: minutes of the meetings, 11 August 2009,
      Montreal, Canada.

PMID- 25386002
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of phototrophic bacteria: minutes of the closed online meeting, 10-30
      June 2014.

PMID- 25386003
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of Halobacteriaceae: minutes of the closed meeting, 31 July 2014,
      Montreal, Canada.

PMID- 25386004
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of Halomonadaceae: minutes of the closed meeting, 31 July 2014,
      Montreal, Canada.

PMID- 25386005
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of Halobacteriaceae and Subcommittee on the taxonomy of Halomonadaceae:
      minutes of the joint open meeting, 31 July 2014, Montreal, Canada.

PMID- 25386007
TI  - The combinations Lysobacter enzymogenes subsp. enzymogenes Christensen and Cook
      1978, L. enzymogenes subsp. cookii Christensen 1978 and Streptococcus
      casseliflavus (Mundt and Graham 1968) Vaughan et al. 1979 were in accordance with
      the International Code of Nomenclature of Bacteria at the time of publication in
      the International Journal of Systematic Bacteriology, but are not to be
      considered to be included on the Approved Lists of Bacterial Names. Opinion 95:
      Judicial Commission of the International Committee on Systematics of Prokaryotes.
AB  - The Judicial Commission affirms that, according to information presented to it,
      the combination Lysobacter enzymogenes subsp. enzymogenes Christensen and Cook
      1978, the combination Lysobacter enzymogenes subsp. cookii Christensen 1978 and
      the combination Streptococcus casseliflavus (Mundt and Graham 1968) Vaughan et
      al. 1979 were in accordance with the wording of the 1975 and 1992 revisions of
      the International Code of Nomenclature of Bacteria but they are not to be
      considered to be included on the Approved Lists of Bacterial Names.

PMID- 25386009
TI  - High frequency of dolutegravir resistance in patients failing a raltegravir
      containing salvage regimen.
AB  - OBJECTIVES: Dolutegravir is a second-generation integrase strand transfer
      inhibitor (InSTI) that has been recently approved by the FDA to treat
      antiretroviral therapy-naive as well as treatment-experienced HIV-infected
      individuals, including those already exposed to the first-generation InSTI.
      Despite having a different mutational profile, some cross-resistance mutations
      may influence its susceptibility. The aim of this study was to evaluate the
      impact of a raltegravir-containing salvage regimen on dolutegravir activity.
      PATIENTS AND METHODS: Blood samples of 92 HIV-infected individuals with
      virological failure (two or more viral loads >50 copies/mL after 6 months of
      treatment) using raltegravir with optimized background therapy were sequenced and
      evaluated according to the Stanford University HIV Drug Resistance Database
      algorithm. RESULTS: Among the 92 patients analysed, 32 (35%) showed resistance to
      dolutegravir, in most cases associated with the combination of Q148H/R/K with
      G140S/A mutations. At genotyping, patients with resistance to dolutegravir had
      viral load values closer to the highest previously documented viral load.
      CONCLUSIONS: Changes in viraemia during virological failure may indicate the
      evolution of raltegravir resistance and may predict the emergence of secondary
      mutations that are associated with a decrease in dolutegravir susceptibility.
      Early discontinuation of raltegravir from failing regimens might favour
      subsequent salvage with dolutegravir, but further studies are necessary to
      evaluate this issue.

PMID- 25386010
TI  - Cost-benefit of Instructional Strategies.

PMID- 25386011
TI  - The challenges of pharmacy education in Yemen.
AB  - Pharmacy education in Yemen has faced many challenges since its introduction in
      the 1980s. Most Yemeni pharmacy schools, especially private ones, are
      experiencing difficulties in providing the right quality and quantity of clinical
      educational experiences. Most of these challenges are imbedded in a teaching
      style and curricula that have failed to respond to the needs of the community and
      country. The slow shift from traditional drug-dispensing to a patient-centered or
      focused approach in pharmacy practice requires a fundamental change in the roles
      and responsibilities of both policymakers and educators. The purpose of this
      paper is twofold: (1) to discuss the challenges facing the pharmacy education in
      Yemen; (2) to provided recommendations to overcome challenges. 

PMID- 25386012
TI  - The effect of transitioning from residency to pharmacy practice on learning
      style.
AB  - OBJECTIVE: To describe the evolution of learning styles of pharmacy residents as
      they transition from residency to practice. METHODS: Cross-sectional survey and
      interview-based study. A complete provincial cohort of former pharmacy residents
      (N=28), who had their learning styles characterized with the Pharmacists'
      Inventory of Learning Styles (PILS) at the beginning of their residency and, 1
      year post-residency, were invited to repeat the PILS. Interviews were
      administered to consenting participants to gain additional insight. RESULTS:
      Twenty-seven of the former residents (96%) completed the PILS survey and 16 (59%)
      completed the post-PILS interview. Thirteen (48%) changed their dominant learning
      style and 20 (74%) changed their secondary learning style. Six (22%) participants
      did not change either learning style. The overall proportion of dominant
      assimilators (59%) and convergers (26%) remained similar to baseline (52% and
      26%, respectively), meaning participants had adopted and abandoned different
      learning style in similar numbers. Change in learning style was associated with
      being a preceptor (p<0.05), as 58% of the 12 former residents who became
      preceptors stated in the interview they had adjusted their teaching practices
      based on knowledge of their learning styles gained during their residency.
      CONCLUSION: Changing learning style is common for former residents after 1 year
      in postresidency practice. There is no overall direction to the change; former
      residents transition into and out of various learning styles with similar
      frequency and retain preferences for passive/abstract learning approaches over
      active/concrete ones. The early-career lability in learning style the study
      demonstrated may reveal an opportunity to guide pharmacists toward more active
      learning preferences through residency curricula, preceptorship, and mentorship.

PMID- 25386013
TI  - Pharmacy students' ability to think about thinking.
AB  - OBJECTIVE: To investigate students' metacognitive skills to distinguish what they
      know from what they do not know, to assess students' prediction of performance on
      a summative examination, and to compare student-identified incorrect questions
      with actual examination performance in order to improve exam quality. METHODS:
      Students completed a test-taking questionnaire identifying items perceived to be
      incorrect and rating their test-taking ability. RESULTS: Higher performing
      students evidenced better metacognitive skills by more accurately identifying
      incorrect items on the exam. Most students (86%) underpredicted their performance
      on the summative examination (actual = 73.6 +/- 7.1 versus predicted = 63.7 +/-
      10.5, p < 0.05). Student responses helped refine items and resulted in
      examination changes. CONCLUSION: Metacognition is important to the development of
      life-long learning in pharmacy students. Students able to monitor what they know
      and what they do not know can improve their performance.

PMID- 25386014
TI  - Addressing the academic gap between 4- and 6-year pharmacy programs in South
      Korea.
AB  - OBJECTIVE: To address the academic gap (or lack of adequate training and
      programs) between 4- and 6-year pharmacy programs and suggest methods for
      reducing this gap and to evaluate pharmacists' perceptions of preceptorship.
      METHODS: We surveyed a convenience sample of 200 community pharmacists who
      graduated from a 4-year program who were participating in a continuing education
      program for clinical pharmacy as organized by the Daejeon branch of the Korea
      Pharmaceutical Association in 2011. Twenty-one questions were asked about the
      academic gap, needs for an education program, preceptorship, and medication
      therapy management services. International precedents were examined through a
      literature review to glean ideas of how to bridge the academic gap between the 4-
      and 6-year programs. RESULTS: In total, 132 pharmacists answered the survey
      (return rate=66.0%). The survey findings included problems caused by the academic
      gap, high need for an adequate education program, low acceptability of
      preceptorship, and the possibility of medication therapy management services. US
      based, non-traditional PharmD programs and new curriculum-support training in
      Japan provided examples of how the academic gap has been successfully bridged.
      CONCLUSION: Nationwide efforts and government support are urgently required to
      close the academic gap, and experiential education should be included in
      transitional programs for 4-year pharmacy program pharmacists.

PMID- 25386015
TI  - Assessing outcomes and perceived benefits of a professional development seminar
      series.
AB  - OBJECTIVE: To evaluate the outcomes of alumni who were enrolled in a professional
      development seminar series during their doctor of pharmacy program. DESIGN: A
      weekly development seminar series was administered over 5 semesters with the goal
      of bringing academic advisees together to help develop performance-based
      abilities, prepare them for entry into the profession after graduation, and
      provide exposure to different career opportunities. ASSESSMENT: A survey
      instrument containing 39 Likert-type scale items, 2 open-ended questions, and a
      10-item demographic survey was created and content-validated to assess the effect
      of the seminar series on alumni advisees' perceived outcomes and professional
      development since their graduation. The survey was electronically forwarded to
      advisees from the graduating classes of 2005 to 2012, and response data was
      collected with Qualtrics, a web-based survey service. A total of 36 percent of
      alumni responded to the survey. Respondents cited exposure to career alternatives
      and opportunities, development of presentation and communication skills,
      networking, and the importance of advisor/mentor relationships as benefits of the
      seminar series. CONCLUSION: The professional development seminar series has
      demonstrated a positive impact on alumni advisees' career development and
      professional outcomes, most notably relating to career path exposure,
      communication skills, and advisor/mentor relationships.

PMID- 25386016
TI  - Development of an antimicrobial stewardship-based infectious diseases elective
      that incorporates human patient simulation technology.
AB  - OBJECTIVE: To design an elective for pharmacy students that facilitates
      antimicrobial stewardship awareness, knowledge, and skill development by solving
      clinical cases, using human patient simulation technology. DESIGN: The elective
      was designed for PharmD students to describe principles and functions of
      stewardship programs, select, evaluate, refine, or redesign patient-specific
      plans for infectious diseases in the context of antimicrobial stewardship, and
      propose criteria and stewardship management strategies for an antimicrobial class
      at a health care institution. Teaching methods included active learning and
      lectures. Cases of bacterial endocarditis and cryptococcal meningitis were
      developed that incorporated human patient simulation technology. ASSESSMENT:
      Forty-five pharmacy students completed an antimicrobial stewardship elective
      between 2010 and 2013. Outcomes were assessed using student perceptions of and
      performance on rubric-graded assignments. CONCLUSION: A PharmD elective using
      active learning, including novel cases conducted with human patient simulation
      technology, enabled outcomes consistent with those desired of pharmacists
      assisting in antimicrobial stewardship programs.

PMID- 25386017
TI  - Measuring preadvanced practice experience outcomes as part of a PharmD capstone
      experience.
AB  - OBJECTIVE: To describe a capstone experience to: 1) assess student preparedness
      for Advanced Pharmacy Practice Experiences (APPE) and 2) provide program-level
      assessment data. DESIGN: A capstone course was added immediately prior to APPEs.
      All capstone activities emphasized application and integration and were mapped to
      ACPE Appendix D, which details performance abilities expected of students prior
      to APPEs. Eleven learning activities comprising 20 assessments were created. Each
      assessment was pass/fail; students had to pass 15 of 20 assessments to pass the
      capstone course. Evaluation rubrics emphasized formative feedback for students.
      ASSESSMENT: The capstone experience was delivered 4 times over 4 consecutive
      years. One student did not pass; 55-68% of the students passed all activities.
      Program-level assessment data provided details on individual student preparedness
      prior to APPE, important information for accreditation, and basis for curriculum
      revisions. CONCLUSION: A capstone experience can be a valuable addition to a
      PharmD curriculum. Capstone activities incorporating authentic assessments
      provide important program-level assessment data for colleges/schools of pharmacy.

PMID- 25386018
TI  - Comparing effectiveness of high-fidelity human patient simulation vs case-based
      learning in pharmacy education.
AB  - OBJECTIVE: To determine whether human patient simulation (HPS) is superior to
      case-based learning (CBL) in teaching diabetic ketoacidosis (DKA) and thyroid
      storm (TS) to pharmacy students. DESIGN: In this cross-over, open-label, single
      center, randomized control trial, final-year undergraduate pharmacy students
      enrolled in an applied therapeutics course were randomized to HPS or CBL groups.
      Pretest, posttest, knowledge retention tests, and satisfaction survey were
      administered to students. ASSESSMENT: One hundred seventy-four students
      participated in this study. The effect sizes attributable to HPS were larger than
      CBL in both cases. HPS groups performed significantly better in posttest and
      knowledge retention test compared to CBL groups pertaining to TS case (p < 0.05).
      Students expressed high levels of satisfaction with HPS sessions. CONCLUSION: HPS
      was superior to CBL in teaching DKA and TS to final-year undergraduate pharmacy
      students.

PMID- 25386019
TI  - The impact of an immersive elective on learners' understanding of lifestyle
      medicine and its role in patients' lives.
AB  - OBJECTIVE: To design an immersive, active learning, lifestyle medicine (LM)
      elective and evaluate its impact on a pharmacy learners' ability to understand
      the challenges of implementing lifestyle changes. DESIGN: A 3-credit elective was
      developed that incorporated goal setting and immersion into the realm of LM as
      experienced by both the patient and the practitioner. Learners were assessed via
      a survey instrument, formal assignments, reflections, and the Presidential
      Fitness Challenge. ASSESSMENT: Learners reported that their ability to initiate
      LM as a primary intervention within a care plan significantly increased after
      taking this course. They also improved their overall health. CONCLUSION: By
      identifying and implementing self-identified lifestyle modifications, learners
      increased confidence in their abilities to produce evidence-based outcomes for
      patients. Learners were able to understand the challenges of trying to change
      their daily habits as they undertook their own personal goals.

PMID- 25386020
TI  - Assessment of student performance and perceptions of learning in a medication use
      evaluation project.
AB  - OBJECTIVE: To describe and assess student perceptions and performance on a
      medication use evaluation (MUE) team project. DESIGN: Following a 1-hour MUE
      lecture in a 62-student patient safety course, student teams (n=14) were assigned
      a medication safety or quality issue. Teams worked with a mentor to design an MUE
      to address the issue. The deliverable was a verbal presentation recorded as a
      webinar. ASSESSMENT: Presentations were assessed by 2 reviewers for content and
      style. Mean score was 45.0 +/- 2.7 of 50 points. Students rated level of
      agreement that they could perform MUE-related skills pre- and postproject (n=35
      and 34, respectively) on a 5-point Likert scale. Students perceived improved
      ability to design an MUE after project completion (median 3 vs 4; p=0.003).
      Student comfort with sample determination, data, collaborators, study
      limitations, and potential project impact also improved. CONCLUSION: Teams
      achieved the objective of successfully designing an MUE, and related enabling
      outcomes (ie, supportive activities that contribute to designing an MUE), as
      measured by evaluators and student perceptions.

PMID- 25386021
TI  - Development of a pharmacy capstone course from focus groups to advanced patient
      care.
AB  - OBJECTIVE: To describe the development of a capstone course using qualitative
      results of focus groups and to determine the impact of the course using a pre-
      and postcourse surveys. DESIGN: A course titled Advanced Patient Care was
      developed using themes emerged from 3 stakeholder focus groups and implemented
      with case-based sessions, interactive exercises, and Objective Structured
      Clinical Examinations (OSCEs). Pre- and postcourse surveys were conducted to
      assess the students' confidence and knowledge in managing 8 commonly-encountered
      conditions. ASSESSMENT: During the 2-year course implementation, a total of 169
      students participated in the pre- and postcourse surveys (87.6% response rate).
      The mean total confidence score increased significantly from 54.3 (+/-9.2) to
      69.0 (+/-8.6, p < 0.001), and the total mean knowledge score increased
      significantly from 6.3 to 6.9 (p < 0.001). CONCLUSION: The capstone course,
      fueled by focus group findings and implemented using interactive sessions and
      simulations, positively impacted students' confidence and knowledge for clinical
      practice experiences and professional practice.

PMID- 25386022
TI  - Development and current status of clinical pharmacy education in China.
AB  - OBJECTIVE: To describe the current status and developing trend of clinical
      pharmacy education in China. METHODS: Descriptive analysis of data and
      information about the clinical pharmacy specialty, pharmacy colleges, and
      curriculum from literature, college websites, and statistics from the Ministry of
      Health (MOH) and Ministry of Education (MOE) websites was conducted. RESULTS:
      Clinical pharmacy programs were established in China in 1989 but developed more
      fully after 2006. In 2012, there were 30 pharmacy colleges with clinical pharmacy
      undergraduate programs, which included a bachelor's degree in clinical pharmacy
      and a clinical pharmacy concentration within the BS programs of pharmacy or
      medicine. More than 40 colleges within the university system offer 4 types of
      master's degree programs in clinical pharmacy. Five universities offer a PhD
      program in clinical pharmacy. Three postgraduate programs exist, which train
      hospital pharmacists and clinical pharmacists: the 3+2 year Hospital Pharmacist
      Standardized Training Program at Peking hospitals; the 1-year Clinical Pharmacist
      Training Program sponsored by the MOH; and the 2-year Clinical Pharmacist
      Residency Program provided by West China Hospital at Sichuan University.
      CONCLUSION: A growing clinical pharmacy education system has been established and
      has become an important subfield in Chinese pharmacy education. Measures should
      be taken to further promote the development of clinical pharmacy education in
      China.

PMID- 25386025
TI  - Three simple words: Report of the Executive Vice President to the House of
      Delegates.

PMID- 25386026
TI  - Crossing the finish line: Address of the 2013-2014 President to the opening
      general session at the AACP annual meeting.

PMID- 25386027
TI  - Access, affordability, accountability: 2013-2014 President-elect address to the
      2014 AACP house of delegates.

PMID- 25386028
TI  - Considerations for embracing and expanding community engaged scholarship in
      academic pharmacy: Report of the 2013-2014 research and graduate affairs
      committee.

PMID- 25386029
TI  - Male moths optimally balance take-off thoracic temperature and warm-up duration
      to reach a pheromone source quickly.
AB  - Animal activities, such as foraging and reproduction, are constrained by
      decisions about how to allocate energy and time efficiently. Overall, male moths
      invest less in reproduction than females, but they are thought to engage in a
      scramble competition for access to females that advertise readiness to mate by
      releasing sexual pheromones. However, before male moths can follow the pheromone,
      they often need to heat their flight muscles by shivering to produce sufficient
      power for sustained flight. Here, we show that Helicoverpa zea males that sense
      the female pheromone at high ambient temperatures take off with higher thoracic
      temperature, shiver for less time and warm up faster than males tested at lower
      ambient temperatures. These higher take-off temperatures translate into higher
      airspeeds, underscoring the importance of thoracic temperature for flight
      performance. Furthermore, shorter combined duration for warm-up and pheromone
      mediated optomotor anemotaxis is consistent with the idea that males engage in
      scramble competition for access to females in nature. Our results strongly
      suggest that male moths minimize the time between perceiving the female's
      pheromone signal and arriving at the source by optimizing thermoregulatory
      behaviour and temperature-dependent flight performance in accordance with ambient
      temperature conditions. Our finding that moths engage in a trade-off between
      rapid flight initiation and suboptimal flight performance suggests a sensorimotor
      control mechanism that involves a complex interaction with the thermal
      environment.

PMID- 25386030
TI  - Critical Factors in the Oral Control Needed for Chewing and Swallowing.
AB  - Normal oropharyngeal swallowing is a complex set of neuromotor behaviors
      containing three phases: 1) Oral preparation to break food down to a swallowable
      consistency; 2) Oral phase which propels food from the mouth; 3) Pharyngeal phase
      creates pressure to push food into the esophagus, and includes valve functions
      which prevent food from entering the nose or airway and allow food into the
      esophagus. Systematic changes in normal oropharyngeal swallow are based on
      volume, viscosity, and taste of the food swallowed as well as age. Patients with
      oropharyngeal swallowing difficulties (dysphagia) react differently to these
      systematic variables in food characteristics. This review manuscript presents the
      results of a series of studies that examine the role of each of the stages of the
      nonoral orpharyngeal swallow. The importance of the definition of food viscosity
      in the care of dysphagic patients and the role of food production companies in
      this effort are emphasized.

PMID- 25386031
TI  - Nonparametric Functional Central Limit Theorem for Time Series Regression with
      Application to Self-normalized Confidence Interval.
AB  - This paper is concerned with the inference of nonparametric mean function in a
      time series context. The commonly used kernel smoothing estimate is
      asymptotically normal and the traditional inference procedure then consistently
      estimates the asymptotic variance function and relies upon normal approximation.
      Consistent estimation of the asymptotic variance function involves another level
      of nonparametric smoothing. In practice, the choice of the extra bandwidth
      parameter can be difficult, the inference results can be sensitive to bandwidth
      selection and the normal approximation can be quite unsatisfactory in small
      samples leading to poor coverage. To alleviate the problem, we propose to extend
      the recently developed self-normalized approach, which is a bandwidth free
      inference procedure developed for parametric inference, to construct point-wise
      confidence interval for nonparametric mean function. To justify asymptotic
      validity of the self-normalized approach, we establish a functional central limit
      theorem for recursive nonparametric mean regression function estimates under
      primitive conditions and show that the limiting process is a Gaussian process
      with non-stationary and dependent increments. The superior finite sample
      performance of the new approach is demonstrated through simulation studies.

PMID- 25386032
TI  - Piezoelectric single crystals for ultrasonic transducers in biomedical
      applications.
AB  - Piezoelectric single crystals, which have excellent piezoelectric properties,
      have extensively been employed for various sensors and actuators applications. In
      this paper, the state-of-art in piezoelectric single crystals for ultrasonic
      transducer applications is reviewed. Firstly, the basic principles and design
      considerations of piezoelectric ultrasonic transducers will be addressed. Then,
      the popular piezoelectric single crystals used for ultrasonic transducer
      applications, including LiNbO3 (LN), PMN-PT and PIN-PMN-PT, will be introduced.
      After describing the preparation and performance of the single crystals, the
      recent development of both the single-element and array transducers fabricated
      using the single crystals will be presented. Finally, various biomedical
      applications including eye imaging, intravascular imaging, blood flow
      measurement, photoacoustic imaging, and microbeam applications of the single
      crystal transducers will be discussed.

PMID- 25386033
TI  - Vaccine against human papilloma virus.

PMID- 25386034
TI  - Burden of disease in Narino, Colombia, 2010.
AB  - OBJECTIVE: This study sought to measure burden of disease and identifies health
      priorities from the Disability Adjusted Life Years (DALYs) indicator. METHODS:
      This is the first study on burden of disease for a department in Colombia by
      using a standardized methodology. By using the. DALYs indicator, burden of
      disease was identified in the department of Narino according to the guidelines
      established by the World Health Organization. RESULTS: The DALYs in the
      Department of Narino highlight the emergence of communicable, maternal,
      perinatal, and nutritional diseases during the first years of life; of accidents
      and lesions among youth, and non-communicable diseases in older individuals.
      Also, accidents and lesions are highlighted in men and non-communicable diseases
      in women. CONCLUSIONS: This study is part of the knowledge management process in
      the Departmental Health Plan for Narino - Colombia 2012-2015 and contributes to
      the system of indicators of the 2012 ten-year public health plan. This research
      evidences that communicable diseases generate the biggest part of the burden of
      disease in the Department of Narino, that DALYs due to non-communicable diseases
      are on the rise, and that accidents and lesions, especially due to violence are
      an important cause of DALYs in this region, which is higher than that of the
      country.

PMID- 25386035
TI  - Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro
      with ionizing radiation.
AB  - OBJECTIVE: To determine the in vitro toxicity of different concentrations of
      sevoflurane in cells exposed to X-ray. METHODS: The genotoxic effects of
      sevofluorane were studied by means of the micronucleus test in cytokinesis
      blocked cells of irradiated human lymphocytes. Subsequently, its cytotoxic
      effects on PNT2 (normal prostate) cells was determined using the cell viability
      test (MTT) and compared with those induced by different doses of X-rays. RESULTS:
      A dose- and time-dependent cytotoxic effect of sevofluorane on PNT2 cells was
      determined (p >0.001) and a dose-dependent genotoxic effect of sevofluorane was
      established (p >0.001). However, at volumes lower than 30 MUL of sevofluorane at
      100%, a non-toxic effect on PNT2 cells was shown. CONCLUSION: Sevofluorane
      demonstrates a genotoxic capacity as determined in vitro by micronucleus test in
      cytokinesis-blocked cells of irradiated human lymphocytes.

PMID- 25386036
TI  - Cancer survival in Cali, Colombia: A population-based study, 1995-2004.
AB  - BACKGROUND: There is limited information on population-based cancer survival data
      in Latin America. OBJECTIVE: To obtain estimates of survival for some cancers
      recognized as a public health priority in Colombia using data from the Cancer
      Registry of Cali for 1995-2004. METHODS: ALL CANCER CASES FOR RESIDENTS OF CALI
      WERE INCLUDED FOR THE FOLLOWING SITES: breast (3,984), cervix uteri (2,469),
      prostate (3,999), stomach (3,442) and lung (2,170). Five-year relative survival
      estimates were calculated using the approach described by Esteve. RESULTS: Five
      year relative survival was 79% in patients with prostate cancer and 68% and 60%
      in women with breast or cervix uteri cancer, respectively. The cure fraction was
      close to zero in subjects with lung cancer and less than 10% in those with
      stomach cancer. The probability of dying from breast or prostate cancer in people
      in the lower socio-economic strata (SES) was 1.8 and 2.6 times, respectively,
      when compared to upper SES, p <0.001. Excess mortality associated with cancer was
      independent of age in prostate or breast cancer. After adjusting for age, sex and
      SES, the risk of dying from breast, cervix uteri, prostate and lung cancer during
      the 2000-2004 period decreased 19%, 13%, 48% and 16%, respectively, when compared
      with the period of 1995-1999. There was no change in the prognosis for patients
      with stomach cancer. CONCLUSIONS: Survival for some kinds of cancer improved
      through the 1995-2004 period, however health care programs for cancer patients in
      Cali are inequitable. People from lower SES are the most vulnerable and the least
      likely to survive.

PMID- 25386037
TI  - Practice of preventive dentistry for nursing staff in primary care.
AB  - OBJECTIVES: Determine the domain of preventive dentistry in nursing personnel
      assigned to a primary care unit. METHODS: Prospective descriptive study,
      questionnaire validation, and prevalence study. In the first stage, the
      questionnaire for the practice of preventive dentistry (CPEP, for the term in
      Spanish) was validated; consistency and reliability were measured by Cronbach's
      alpha, Pearson's correlation, factor analysis with intra-class correlation
      coefficient (ICC). In the second stage, the domain in preventive dental nurses
      was explored. RESULTS: The overall internal consistency of CPEP is alpha= 0.66,
      ICC= 0.64, CI95%: 0.29-0.87 (p >0.01). Twenty-one subjects in the study, average
      age 43, 81.0% female, average seniority of 12.5 were included. A total of 71.5%
      showed weak domain, 28.5% regular domain, and there was no questionnaire with
      good domain result. The older the subjects were, the smaller the domain; female
      nurses showed greater mastery of preventive dentistry (29%, CI95%: 0.1-15.1) than
      male nurses. Public health nurses showed greater mastery with respect to other
      categories (50%, CI95%: 0.56-2.8). CONCLUSIONS: The CDEP has enough consistency
      to explore the domain of preventive dentistry in health-care staff. The domain of
      preventive dentistry in primary care nursing is poor, required to strengthen to
      provide education in preventive dentistry to the insured population.

PMID- 25386038
TI  - Frontotemporal dementia: clinical, neuropsychological, and neuroimaging
      description.
AB  - OBJECTIVE: Describe the relationships between the clinical, neuropsychological,
      and imaging findings from a group of patients diagnosed with frontotemporal
      dementia (FTD). METHODS: The clinical histories, cognitive tests, and structural
      and perfusion brain images of 21 patients of the Psychiatric Hospital
      Universitario del Valle, Cali, Colombia, were reviewed. RESULTS: The average age
      was 59.8 years; the average time for the evolution of disease symptoms was 2.7
      years; the most common variant was the behavioral variant; the most common
      alteration shown through nuclear magnetic resonance (NMR) was frontotemporal
      atrophy, while the most common alteration shown through single-photon emission
      computed tomography (SPECT) was frontotemporal hypoperfusion. The most
      significant result was the normal performance of 61.9% of patients in praxis
      exams, which was associated with alterations in temporoparietal perfusion in the
      SPECT images (p <0.02). Neither the mini-mental state evaluation nor the Clock
      Drawing Executive Test (CLOX) served as screening tests.

PMID- 25386039
TI  - Surgical management of middle ear cholesteatoma and reconstruction at the same
      time.
AB  - INTRODUCTION: In the surgical management of cholesteatoma, one can opt for a
      closed technique (simple mastoidectomy) or open surgery (radical mastoidectomy).
      Open mastoidectomy with reconstruction of the posterior wall and the middle ear
      in a single surgery combines the advantages of both techniques, namely, adequate
      surgical exposure, eradication of cholesteatoma, and anatomical reconstruction of
      the middle ear structures. OBJECTIVE: To evaluate the surgical results in the
      management of cholesteatoma through the technique of open mastoidectomy with
      reconstruction of the posterior wall and the middle ear in a single surgery.
      METHODS: Prospective analytical observational study conducted between 2009 and
      2012 with patients undergoing this surgical technique in the Hospital
      Universitario del Valle [University Hospital of Valle], performing preoperative
      clinical monitoring and quarterly postoperative tomography with previous
      assessments of hearing and pre- and postoperative audiometry. RESULTS: Forty-five
      patients were studied. Mean postoperative follow-up was 28 months. Surgical
      success was achieved in 93.3% of patients, as measured by clinical and
      radiological follow-up. Hearing preservation was found after reconstruction of
      the hearing mechanism, based on measured audiometry, i.e., pure-tone average
      (PTA), using the statistical test for paired samples between preoperative and
      postoperative PTA. (95%CI -1.47-12.15). Residual cholesteatoma was present in
      6.6% of cases; three to four times lower than the rate reported in the
      literature. CONCLUSIONS: This type of surgery can be considered a successful
      technique in the treatment of cholesteatoma in selected cases.

PMID- 25386040
TI  - Injuries are not accidents: towards a culture of prevention.
AB  - Injuries are the result of an acute exposure to exhort of energy or a consequence
      of a deficiency in a vital element that exceeds physiological thresholds
      resulting threatens life. They are classified as intentional or unintentional.
      Injuries are considered a global health issue because they cause more than 5
      million deaths per year worldwide and they are an important contributor to the
      burden of disease, especially affecting people of low socioeconomic status in low
      and middle-income countries. A common misconception exists where injuries are
      thought to be the same as accidents; however, accidents are largely used as
      chance events, without taken in consideration that all these are preventable.
      This review discusses injuries and accidents in the context of road traffic and
      emphasizes injuries as preventable events. An understanding of the essence of
      injuries enables the standardization of terminology in public use and facilitates
      the development of a culture of prevention among all of us.

PMID- 25386041
TI  - Considerations on immunization anxiety-related reactions in clusters.
AB  - A cluster of adverse events following immunization (AEFI) represents a stress
      test for an immunization program. The community can suspect on vaccine-related
      reaction leading to mistrust on the immunization program. An immunization anxiety
      related reaction is one of the hypotheses to be tested and can be reasonably
      accepted when the vaccine-related and immunization error-related reactions are
      ruled out and no coincidental events can explain the cases. Immunization program
      approaches widely accepted to understand and respond to adverse events are root
      cause analysis and systems analysis. Psychiatric cognitive frame will support the
      root-cause analysis assigning a causal relationship to individual temporary
      disorders of the affected vaccinees. Communication will focus on vaccine safety
      and absence of errors in the immunization program. Systems analysis addresses the
      whole context considering the fear spread as a systemic threat. Socio
      psychological frame offers a broader opportunity to understand and respond to a
      specific community. Management is based on communication to change community
      belief in misperceptions of vaccine risks and support the idea of immunization as
      a causal factor, different from the vaccine. Communities can consider use of
      psychiatric labels, Mass Psychogenic Illness or Mass Hysteria, as an act of
      inconsiderateness. Labels like immunization anxiety-related reactions in clusters
      or collective immunization anxiety-related reactions are recommended to bridge
      the causal perception of the community with the result of the scientific
      investigation of the cases.

PMID- 25386042
TI  - A random forest approach for predicting the presence of Echinococcus
      multilocularis intermediate host Ochotona spp. presence in relation to landscape
      characteristics in western China.
AB  - Understanding distribution patterns of hosts implicated in the transmission of
      zoonotic disease remains a key goal of parasitology. Here, random forests are
      employed to model spatial patterns of the presence of the plateau pika (Ochotona
      spp.) small mammal intermediate host for the parasitic tapeworm Echinococcus
      multilocularis which is responsible for a significant burden of human zoonoses in
      western China. Landsat ETM+ satellite imagery and digital elevation model data
      were utilized to generate quantified measures of environmental characteristics
      across a study area in Sichuan Province, China. Land cover maps were generated
      identifying the distribution of specific land cover types, with landscape metrics
      employed to describe the spatial organisation of land cover patches. Random
      forests were used to model spatial patterns of Ochotona spp. presence, enabling
      the relative importance of the environmental characteristics in relation to
      Ochotona spp. presence to be ranked. An index of habitat aggregation was
      identified as the most important variable in influencing Ochotona spp. presence,
      with area of degraded grassland the most important land cover class variable. 71%
      of the variance in Ochotona spp. presence was explained, with a 90.98% accuracy
      rate as determined by 'out-of-bag' error assessment. Identification of the
      environmental characteristics influencing Ochotona spp. presence enables us to
      better understand distribution patterns of hosts implicated in the transmission
      of Em. The predictive mapping of this Em host enables the identification of human
      populations at increased risk of infection, enabling preventative strategies to
      be adopted.

PMID- 25386043
TI  - Interaction Screening for Ultra-High Dimensional Data.
AB  - In ultra-high dimensional data analysis, it is extremely challenging to identify
      important interaction effects, and a top concern in practice is computational
      feasibility. For a data set with n observations and p predictors, the augmented
      design matrix including all linear and order-2 terms is of size n * (p2 + 3p)/2.
      When p is large, say more than tens of hundreds, the number of interactions is
      enormous and beyond the capacity of standard machines and software tools for
      storage and analysis. In theory, the interaction selection consistency is hard to
      achieve in high dimensional settings. Interaction effects have heavier tails and
      more complex covariance structures than main effects in a random design, making
      theoretical analysis difficult. In this article, we propose to tackle these
      issues by forward-selection based procedures called iFOR, which identify
      interaction effects in a greedy forward fashion while maintaining the natural
      hierarchical model structure. Two algorithms, iFORT and iFORM, are studied.
      Computationally, the iFOR procedures are designed to be simple and fast to
      implement. No complex optimization tools are needed, since only OLS-type
      calculations are involved; the iFOR algorithms avoid storing and manipulating the
      whole augmented matrix, so the memory and CPU requirement is minimal; the
      computational complexity is linear in p for sparse models, hence feasible for p ?
      n. Theoretically, we prove that they possess sure screening property for ultra
      high dimensional settings. Numerical examples are used to demonstrate their
      finite sample performance.

PMID- 25386044
TI  - Dowry Deaths: Response to Weather Variability in India.
AB  - We examine the effect of rainfall shocks on dowry deaths using data from 583
      Indian districts for 2002-2007. We find that a one standard deviation decline in
      annual rainfall from the local mean increases reported dowry deaths by 7.8
      percent. Wet shocks have no apparent effect. We examine patterns of other crimes
      to investigate whether an increase in general unrest during economic downturns
      explains the results but do not find supportive evidence. Women's political
      representation in the national parliament has no apparent mitigating effect on
      dowry deaths.

PMID- 25386045
TI  - How to Fully Represent Expert Information about Imprecise Properties in a
      Computer System - Random Sets, Fuzzy Sets, and Beyond: An Overview.
AB  - To help computers make better decisions, it is desirable to describe all our
      knowledge in computer-understandable terms. This is easy for knowledge described
      in terms on numerical values: we simply store the corresponding numbers in the
      computer. This is also easy for knowledge about precise (well-defined) properties
      which are either true or false for each object: we simply store the corresponding
      "true" and "false" values in the computer. The challenge is how to store
      information about imprecise properties. In this paper, we overview different ways
      to fully store the expert information about imprecise properties. We show that in
      the simplest case, when the only source of imprecision is disagreement between
      different experts, a natural way to store all the expert information is to use
      random sets; we also show how fuzzy sets naturally appear in such random-set
      representation. We then show how the random-set representation can be extended to
      the general ("fuzzy") case when, in addition to disagreements, experts are also
      unsure whether some objects satisfy certain properties or not.

PMID- 25386046
TI  - NF-kappaB/AP-1-targeted inhibition of macrophage-mediated inflammatory responses
      by depigmenting compound AP736 derived from natural 1,3-diphenylpropane skeleton.
AB  - AP736 was identified as an antimelanogenic drug that can be used for the
      prevention of melasma, freckles, and dark spots in skin by acting as a suppressor
      of melanin synthesis and tyrosinase expression. Since macrophage-mediated
      inflammatory responses are critical for skin health, here we investigated the
      potential anti-inflammatory activity of AP736. The effects of AP736 on various
      inflammatory events such as nitric oxide (NO)/prostaglandin (PG) E2 production,
      inflammatory gene expression, phagocytic uptake, and morphological changes were
      examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of
      both NO and PGE2 in lipopolysaccharide- (LPS-) treated RAW264.7 cells. In
      addition, AP736 strongly inhibited both LPS-induced morphological changes and
      FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the
      expression of multiple inflammatory genes, such as inducible NO synthase (iNOS),
      cyclooxygenase- (COX-) 2, and interleukin- (IL-) 1beta in LPS-treated RAW264.7
      cells. Transcription factor analysis, including upstream signalling events,
      revealed that both NF-kappaB and AP-1 were targeted by AP736 via inhibition of
      the IKK/IkappaBalpha and IRAK1/TAK1 pathways. Therefore, our results strongly
      suggest that AP736 is a potential anti-inflammatory drug due to its suppression
      of NF-kappaB-IKK/IkappaBalpha and AP-1-IRAK1/TAK1 signalling, which may make
      AP736 useful for the treatment of macrophage-mediated skin inflammation. 

PMID- 25386047
TI  - Epigallocatechin gallate attenuates proliferation and oxidative stress in human
      vascular smooth muscle cells induced by interleukin-1beta via heme oxygenase-1.
AB  - Proliferation of vascular smooth muscle cells (VSMCs) triggered by inflammatory
      stimuli and oxidative stress contributes importantly to atherogenesis. The
      association of green tea consumption with cardiovascular protection has been well
      documented in epidemiological observations, however, the underlying mechanisms
      remain unclear. This study aimed to elucidate the effects of the most active
      green tea catechin derivative, (-)-epigallocatechin-3-gallate (EGCG), in human
      aortic smooth muscle cells (HASMCs), focusing particularly on the role of a
      potent anti-inflammatory and antioxidative enzyme heme oxygenase-1 (HO-1). We
      found that pretreatment of EGCG dose- and time-dependently induced HO-1 protein
      levels in HASMCs. EGCG inhibited interleukin- (IL-)1beta-induced HASMC
      proliferation and oxidative stress in a dose-dependent manner. The HO-1 inducer
      CoPPIX decreased IL-1beta-induced cell proliferation, whereas the HO-1 enzyme
      inhibitor ZnPPIX significantly reversed EGCG-caused growth inhibition in IL-1beta
      treated HASMCs. At the molecular level, EGCG treatment significantly activated
      nuclear factor erythroid-2-related factor (Nrf2) transcription activities. These
      results suggest that EGCG might serve as a complementary and alternative medicine
      in the treatment of these pathologies by inducing HO-1 expression and
      subsequently decreasing VSMC proliferation. 

PMID- 25386048
TI  - Scropolioside B inhibits IL-1beta and cytokines expression through NF-kappaB and
      inflammasome NLRP3 pathways.
AB  - Chronic inflammation is associated with various chronic illnesses including
      immunity disorders, cancer, neurodegeneration, and vascular diseases. Iridoids
      are compounds with anti-inflammatory properties. However their anti-inflammatory
      mechanism remains unclear. Here, we report that scropolioside B, isolated from a
      Tibetan medicine (Scrophularia dentata Royle ex Benth.), blocked expressions of
      TNF, IL-1, and IL-32 through NF-kappaB pathway. Scropolioside B inhibited NF
      kappaB activity in a dose-dependent manner with IC50 values of 1.02 MUmol/L.
      However, catalpol, similar to scropolioside B, was not effective in inhibiting NF
      kappaB activity. Interestingly, scropolioside B and catalpol decreased the
      expression of NLRP3 and cardiolipin synthetase at both the mRNA and protein
      level. Our results showed that scropolioside B is superior in inhibiting the
      expression, maturation, and secretion of IL-1beta compared to catalpol. These
      observations provide further understanding of the anti-inflammatory effects of
      iridoids and highlight scropolioside B as a potential drug for the treatment of
      rheumatoid arthritis and atherosclerosis.

PMID- 25386049
TI  - Current surgical treatment strategies for hepatocellular carcinoma in North
      America.
AB  - Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the
      setting of chronic liver disease. Many patients do not initially manifest any
      symptoms of HCC and present late when cure with surgical resection or
      transplantation is no longer possible. For this reason, patients at high risk for
      developing HCC are subjected to frequent screening processes. The surgical
      management of HCC is complex and requires an inter-disciplinary approach. Hepatic
      resection is the treatment of choice for HCC in patients without cirrhosis and is
      indicated in some patients with early cirrhosis (Child-Pugh A). Liver
      transplantation has emerged in the past decade as the standard of care for
      patients with cirrhosis and HCC meeting Milan criteria and in select patients
      with HCC beyond Milan criteria. Loco-regional therapy with transarterial
      chemoembolization, transarterial embolization, radiofrequency ablation and other
      similar local treatments can be used as neo-adjuvant therapy to downstage HCC to
      within Milan criteria or as a bridge to transplantation in patients on transplant
      wait list. 

PMID- 25386050
TI  - Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral
      hepatitis of hepatocellular carcinoma.
AB  - Epidemiological and clinical data point to a close association between chronic
      hepatitis B virus infection or chronic hepatitis C virus infection and
      development of hepatocellular carcinoma (HCC). HCC develops over several decades
      and is associated with fibrosis. This sequence suggests that persistent viral
      infection and chronic inflammation can synergistically induce liver fibrosis and
      hepatocarcinogenesis. The transforming growth factor-beta (TGF-beta) signaling
      pathway plays a pivotal role in diverse cellular processes and contributes to
      hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic
      liver diseases. The biological activities of TGF-beta are initiated by the
      binding of the ligand to TGF-beta receptors, which phosphorylate Smad proteins.
      TGF-beta type I receptor activates Smad3 to create COOH-terminally phosphorylated
      Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates
      Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver
      disease progression, virus components, together with pro-inflammatory cytokines
      and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to
      fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing
      the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide
      new opportunities for effective chemoprevention and personalized therapy for
      patients with hepatitis virus-related HCC in the future. 

PMID- 25386051
TI  - Safety of hepatectomy for elderly patients with hepatocellular carcinoma.
AB  - The number of elderly patients with hepatocellular carcinoma (HCC) has been
      increasing. Characteristics of elderly HCC patients are a higher proportion of
      females, a lower rate of positive hepatitis B surface antigen, and a higher rate
      of positive hepatitis C antibodies. Careful patient selection is vital for
      performing hepatectomy safely in elderly HCC patients. Treatment strategy should
      be decided by not only considering tumor stage and hepatic functional reserve,
      but also physiological status, including comorbid disease. Various assessment
      tools have been applied to predict the risk of hepatectomy. The reported
      mortality and morbidity rates after hepatectomy in elderly HCC patients ranged
      from 0% to 42.9% and from 9% to 51%, respectively. Overall survival rate after
      hepatectomy in elderly HCC patients at 5 years ranged from 26% to 75.9%. Both
      short-term and long-term results after hepatectomy for strictly selected elderly
      HCC patients are almost the same as those for younger patients. However,
      considering physiological characteristics and the high prevalence of comorbid
      disease in elderly patients, it is important to assess patients more meticulously
      and to select them strictly if scheduled to undergo major hepatectomy. 

PMID- 25386052
TI  - Immunogenetic biomarkers in inflammatory bowel diseases: role of the IBD3 region.
AB  - Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23),
      an area which encompasses the famous human leukocyte antigen (HLA) complex, and
      Crohn's disease (CD) or ulcerative colitis (UC). IBD3 is the only region that
      meets genome-wide significance, and provides stronger evidence of the linkage
      than 16p13.1-16q12.2 (IBD1), the locus that contains the susceptibility gene
      CARD15. However, despite these findings, IBD3 susceptibility genes remain elusive
      and unclear due to the strong linkage disequilibrium, extensive polymorphism, and
      high gene density that characterize this area and also due to varying allele
      frequencies in populations around the world. This area presents an extremely high
      abundance of genes, including the classical and non-classical major
      histocompatibility complex (MHC) class I and II genes, and other genes, namely
      MHC class III genes tumor necrosis factor (TNF)-alpha and -beta, and Hsp, whose
      proteins play key functions in immunological processes. To date, it is not clear
      which genes within the MHC family contribute to the IBD pathogenesis, although
      certain HLA alleles have been associated with IBD. Recent insights into the
      biological function of other genes encoded within the IBD3 region, such as the
      MHC class I chain-related (MIC) genes, have led investigators to a more
      comprehensive exploration of this region. MHC class I chain-related molecule A
      (MICA) is highly polymorphic and interacts with NKG2D, its receptor on the
      surface of NK, Tgammadelta and T CD8(+) cells. Increased expression of MICA in
      intestinal epithelial cells and increased expression of NKG2D in CD4(+) T cells
      (lamina propria) in patients with CD have also been reported. MICA alleles have
      also been associated with IBD, and a variation at amino acid position 129 of the
      alpha2-heavy chain domain seems to categorize MICA alleles into strong and weak
      binders of NKG2D receptor, thereby influencing the effector cells' function. In
      this regard, a relevant role of MICA-129-Val/Met single nucleotide polymorphism
      has recently been implicated in the pathogenesis of IBD. TNF-alpha and -beta also
      play an important role in inflammatory response. In fact, IBD is commonly treated
      with TNF-alpha inhibitors. Additionally, polymorphisms of TNF-alpha gene are
      known to affect the gene expression level and particular TNF-alpha genotypes may
      influence the response of IBD patients treated with TNF-alpha inhibitors.

PMID- 25386053
TI  - Prognostic and predictive response factors in colorectal cancer patients: between
      hope and reality.
AB  - Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers
      worldwide. It is the second leading cause of cancer death in Western Countries.
      In the last decade the survival of patients with metastatic CRC has improved
      dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and
      target therapies (i.e., bevacizumab, cetuximab and panitumab), the median overall
      survival has risen from about 12 mo in the mid nineties to 30 mo recently. Many
      questions needing of right collocations and more clearness still exist regarding
      the prognostic factors and the predictive factors of response to therapy. Despite
      advances in dosing and scheduling of chemotherapy in both adjuvant and advanced
      settings, and a greater emphasis on early detection, the outlook still remains
      poor for most patients. Molecular analyses have shown that the natural history of
      all CRCs is not the same. Individual patients with same stage tumours may have
      different long term prognosis and response to therapy. In addition, some
      prognostic variables are likely to be more important than others. Here we review
      the role of prognostic factors and predictive factors according to the recently
      published English literature. 

PMID- 25386054
TI  - Primary prevention of colorectal cancer: myth or reality?
AB  - Colorectal cancer incidence has been rising strongly in parallel with economic
      development. In the past few decades, much has been learned about the lifestyle,
      dietary and medication risk factors for this malignancy. With respect to
      lifestyle, compelling evidence indicates that prevention of weight gain and
      maintenance of a reasonable level of physical activity can positively influence
      in lowering the risk. Although there is controversy about the role of specific
      nutritional factors, consideration of dietary pattern as a whole appears useful
      for formulating recommendations. Though quite often recommended, the role for
      many supplements, including omega-3, vitamin D, folate, and vitamin B6, remains
      unsettled. Only calcium and vitamin D supplementation appear to add a modest
      benefit, particularly in those with a low daily intake. With regard to
      chemoprevention, medications such as aspirin and nonsteroidal anti-inflammatory
      drugs, and postmenopausal hormonal replacement for women might be associated with
      substantial reductions in colorectal cancer risk, though their utility is
      affected by their side effect profile. However, the role of agents such as
      statins, bisphosphonates and antioxidants have yet to be determined. Ultimately,
      primary prevention strategies focusing on modifying environmental, lifestyle risk
      factors, and chemopreventive drugs are options that have already been tested, and
      may impact on colon cancer incidence. 

PMID- 25386055
TI  - Systems biology approaches for studying the pathogenesis of non-alcoholic fatty
      liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a progressive disease of increasing
      public health concern. In western populations the disease has an estimated
      prevalence of 20%-40%, rising to 70%-90% in obese and type II diabetic
      individuals. Simplistically, NAFLD is the macroscopic accumulation of lipid in
      the liver, and is viewed as the hepatic manifestation of the metabolic syndrome.
      However, the molecular mechanisms mediating both the initial development of
      steatosis and its progression through non-alcoholic steatohepatitis to
      debilitating and potentially fatal fibrosis and cirrhosis are only partially
      understood. Despite increased research in this field, the development of non
      invasive clinical diagnostic tools and the discovery of novel therapeutic targets
      has been frustratingly slow. We note that, to date, NAFLD research has been
      dominated by in vivo experiments in animal models and human clinical studies.
      Systems biology tools and novel computational simulation techniques allow the
      study of large-scale metabolic networks and the impact of their dysregulation on
      health. Here we review current systems biology tools and discuss the benefits to
      their application to the study of NAFLD. We propose that a systems approach
      utilising novel in silico modelling and simulation techniques is key to a more
      comprehensive, better targeted NAFLD research strategy. Such an approach will
      accelerate the progress of research and vital translation into clinic. 

PMID- 25386056
TI  - MicroRNAs as controlled systems and controllers in non-alcoholic fatty liver
      disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a multi-faceted condition including
      simple steatosis alone or associated with inflammation and ballooning (non
      alcoholic steatohepatitis) and eventually fibrosis. The NAFLD incidence has
      increased over the last twenty years becoming the most frequent chronic liver
      disease in industrialized countries. Obesity, visceral adiposity, insulin
      resistance, and many other disorders that characterize metabolic syndrome are the
      major predisposing risk factors for NAFLD. Furthermore, different factors,
      including genetic background, epigenetic mechanisms and environmental factors,
      such as diet and physical exercise, contribute to NAFLD development and
      progression. Several lines of evidence demonstrate that specific microRNAs
      expression profiles are strongly associated with several pathological conditions
      including NAFLD. In NAFLD, microRNA deregulation in response to intrinsic genetic
      or epigenetic factors or environmental factors contributes to metabolic
      dysfunction. In this review we focused on microRNAs role both as controlled and
      controllers molecules in NAFLD development and/or their eventual value as non
      invasive biomarkers of disease. 

PMID- 25386057
TI  - Hypoxia and fatty liver.
AB  - The liver is a central organ that metabolizes excessive nutrients for storage in
      the form of glycogen and lipids and supplies energy-producing substrates to the
      peripheral tissues to maintain their function, even under starved conditions.
      These processes require a considerable amount of oxygen, which causes a steep
      oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or
      excessive food intake can alter the hepatic metabolic balance drastically, which
      can precipitate fatty liver disease, a major cause of chronic liver diseases
      worldwide, ranging from simple steatosis, through steatohepatitis and hepatic
      fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in
      fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in
      severe liver hypoxia. As master regulators of adaptive responses to hypoxic
      stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ
      functions, including erythropoiesis, angiogenesis, metabolic demand, and cell
      survival, by activating their target genes during fetal development and also in
      many disease conditions such as cancer, heart failure, and diabetes. In the past
      decade, it has become clear that HIFs serve as key factors in the regulation of
      lipid metabolism and fatty liver formation. This review discusses the molecular
      mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development
      and progression of fatty liver disease. 

PMID- 25386058
TI  - Prevention of esophageal strictures after endoscopic submucosal dissection.
AB  - Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD)
      have recently been accepted as less invasive methods for treating patients with
      early esophageal cancers such as squamous cell carcinoma and dysplasia of
      Barrett's esophagus. However, the large defects in the esophageal mucosa often
      cause severe esophageal strictures, which dramatically reduce the patient's
      quality of life. Although preventive endoscopic balloon dilatation can reduce
      dysphagia and the frequency of dilatation, other approaches are necessary to
      prevent esophageal strictures after ESD. This review describes several strategies
      for preventing esophageal strictures after ESD, with a particular focus on anti
      inflammatory and tissue engineering approaches. The local injection of
      triamcinolone acetonide and other systemic steroid therapies are frequently used
      to prevent esophageal strictures after ESD. Tissue engineering approaches for
      preventing esophageal strictures have recently been applied in basic research
      studies. Scaffolds with temporary stents have been applied in five cases, and
      this technique has been shown to be safe and is anticipated to prevent esophageal
      strictures. Fabricated autologous oral mucosal epithelial cell sheets to cover
      the defective mucosa similarly to how commercially available skin products
      fabricated from epidermal cells are used for skin defects or in cases of
      intractable ulcers. Fabricated autologous oral-mucosal-epithelial cell sheets
      have already been shown to be safe. 

PMID- 25386059
TI  - S-1 in the treatment of pancreatic cancer.
AB  - S-1 is an oral 5-fluorouracil (5-FU) prodrug, which is designed to improve the
      antitumor activity of 5-FU by inhibiting dihydropyrimidine dehydrogenase, the key
      enzyme of 5-FU catabolism. Recently, two important studies on the clinical use of
      S-1 for pancreatic cancer have been reported from Japan. In the first study (GEST
      study), S-1 demonstrated non-inferiority to gemcitabine (GEM) in overall survival
      (OS) for metastatic or locally advanced pancreatic cancer, but combination
      chemotherapy with GEM and S-1 did not show superiority to GEM in OS. In the
      second study (JASPAC-01 study), S-1 showed superiority to adjuvant chemotherapy
      with GEM in OS in patients with resected pancreatic cancer. In addition to GEM, S
      1 is now regarded as the key drug in the management of pancreatic cancer in
      Japan. To date, many studies have investigated the effectiveness of S-1 in
      various settings, such as first-line chemotherapy for metastatic or locally
      advanced pancreatic cancer, second-line chemotherapy after GEM failure, and
      chemoradiotherapy for locally advanced disease. In this review, we focus on
      recent clinical trials of S-1-based chemotherapy for advanced pancreatic cancer. 

PMID- 25386060
TI  - Evolution and future of laparoscopic colorectal surgery.
AB  - The advances of laparoscopic surgery since the early 1990s have caused one of the
      largest technical revolutions in medicine since the detection of antibiotics
      (1922, Flemming), the discovery of DNA structure (1953, Watson and Crick), and
      solid organ transplantation (1954, Murray). Perseverance through a rocky start
      and increased familiarity with the chop-stick surgery in conjunction with
      technical refinements has resulted in a rapid expansion of the indications for
      minimally invasive surgery. Procedure-related factors initially contributed to
      this success and included the improved postoperative recovery and cosmesis, fewer
      wound complications, lower risk for incisional hernias and for subsequent
      adhesion-related small bowel obstructions; the major breakthrough however came
      with favorable long-term outcomes data on oncological parameters. The future will
      have to determine the specific role of various technical approaches, define
      prognostic factors of success and true progress, and consider directing further
      innovation while potentially limiting approaches that do not add to patient
      outcomes. 

PMID- 25386061
TI  - Current status of laparoscopy for the treatment of rectal cancer.
AB  - Surgery for rectal cancer in complex and entails many challenges. While the
      laparoscopic approach in general and specific to colon cancer has been long
      proven to have short term benefits and to be oncologically safe, it is still a
      debatable topic for rectal cancer. The attempt to benefit rectal cancer patients
      with the known advantages of the laparoscopic approach while not compromising
      their oncologic outcome has led to the conduction of many studies during the past
      decade. Herein we describe our technique for laparoscopic proctectomy and assess
      the current literature dealing with short term outcomes, immediate oncologic
      measures (such as lymph node yield and specimen quality) and long term oncologic
      outcomes of laparoscopic rectal cancer surgery. We also briefly evaluate the
      evolving issues of robotic assisted rectal cancer surgery and the current
      innovations and trends in the minimally invasive approach to rectal cancer
      surgery. 

PMID- 25386062
TI  - Laparoscopic revolution in bariatric surgery.
AB  - The history of bariatric surgery is investigational. Dedicated surgeons have
      continuously sought for an ideal procedure to relieve morbidly obese patients
      from their burden of comorbid conditions, reduced life expectancy and low quality
      of life. The ideal procedure must have low complication risk, both in short- and
      long term, as well as minimal impact on daily life. The revolution of
      laparoscopic techniques in bariatric surgery is described in this summary.
      Advances in minimal invasive techniques have contributed to reduced operative
      time, length of stay, and complications. The development in bariatric surgery has
      been exceptional, resulting in a dramatic increase of the number of procedures
      performed world wide during the last decades. Although, a complex bariatric
      procedure can be performed with operative mortality no greater than
      cholecystectomy, specific procedure-related complications and other drawbacks
      must be taken into account. The evolution of laparoscopy will be the legacy of
      the 21(st) century and at present, day-care surgery and further reduction of the
      operative trauma is in focus. The impressive effects on comorbid conditions have
      prompted the adoption of minimal invasive bariatric procedures into the field of
      metabolic surgery. 

PMID- 25386063
TI  - Single-session minimally invasive management of common bile duct stones.
AB  - Up to 18% of patients submitted to cholecystectomy had concomitant common bile
      duct stones. To avoid serious complications, these stones should be removed.
      There is no consensus about the ideal management strategy for such patients.
      Traditionally, open surgery was offered but with the advent of endoscopic
      retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy (LC)
      minimally invasive approach had nearly replaced laparotomy because of its well
      known advantages. Minimally invasive approach could be done in either two-session
      (preoperative ERCP followed by LC or LC followed by postoperative ERCP) or single
      session (laparoscopic common bile duct exploration or LC with intraoperative
      ERCP). Most recent studies have found that both options are equivalent regarding
      safety and efficacy but the single-session approach is associated with shorter
      hospital stay, fewer procedures per patient, and less cost. Consequently, single
      session option should be offered to patients with cholecysto-choledocholithiaisis
      provided that local resources and expertise do exist. However, the management
      strategy should be tailored according to many variables, such as available
      resources, experience, patient characteristics, clinical presentations, and
      surgical pathology. 

PMID- 25386064
TI  - Laparoscopy in the management of hilar cholangiocarcinoma.
AB  - The use of minimally invasive surgery has become widely accepted in many
      gastrointestinal fields, even in patients with malignancy. However, performing
      laparoscopic resection for the treatment of hilar cholangiocarcinoma is still not
      universally accepted as an alternative approach to open surgery, and only a
      limited number of such procedures have been reported due to the difficulty of
      performing oncologic resection and the lack of consensus regarding the adequacy
      of this approach. Laparoscopy was initially limited to staging, biopsy and
      palliation. Recent technological developments and improvements in endoscopic
      procedures have greatly expanded the applications of laparoscopic liver resection
      and lymphadenectomy, and some reports have described the use of laparoscopic or
      robot-assisted laparoscopic resection for hilar cholangiocarcinoma as being
      feasible and safe in highly selected cases, with the ability to obtain an
      adequate surgical margin. However, the benefits of major laparoscopic surgery
      have yet to be conclusively proven, and carefully selecting patients is essential
      for successfully performing this procedure. 

PMID- 25386065
TI  - Laparoscopic excision of Meckel's diverticulum in children: what is the current
      evidence?
AB  - Complications aroused from Meckel's diverticulum tend to developed in children.
      Children presented with abdominal pain, intestinal obstruction, intussusception
      or gastrointestinal bleeding may actually suffered from complicated Meckel's
      diverticulum. With the advancement of minimally invasive surgery (MIS) in
      children, the use of laparoscopy in the diagnosis and subsequent laparoscopic
      excision of Meckel's diverticulum has gained popularity. Recently, single
      incision laparoscopic surgery (SILS) has emerged as a new technique in minimally
      invasive surgery. This review offers the overview in the development of MIS in
      the management of children suffered from Meckel's diverticulum. The current
      evidence in different laparoscopic techniques, including conventional
      laparoscopy, SILS, the use of special laparoscopic instruments, intracorporeal
      diverticulectomy and extracorporeal diverticulectomy in the management of
      Meckel's diverticulum in children were revealed. 

PMID- 25386067
TI  - Autoimmune pancreatitis in the context of IgG4-related disease: review of imaging
      findings.
AB  - Current understanding of autoimmune pancreatitis (AIP) recognizes a
      histopathological subtype of the disease to fall within the spectrum of IgG4
      related disease. Along with clinical, laboratory, and histopathological data,
      imaging plays an important role in the diagnosis and management of AIP, and more
      broadly, within the spectrum of IgG4-related disease. In addition to the defined
      role of imaging in consensus diagnostic protocols, an array of imaging modalities
      can provide complementary data to address specific clinical concerns. These
      include contrast-enhanced computed tomography (CT) and magnetic resonance (MR)
      imaging for pancreatic parenchymal lesion localization and characterization,
      endoscopic retrograde and magnetic resonance cholangiopancreatography (ERCP and
      MRCP) to assess for duct involvement, and more recently, positron emission
      tomography (PET) imaging to assess for extra-pancreatic sites of involvement.
      While the imaging appearance of AIP varies widely, certain imaging features are
      more likely to represent AIP than alternate diagnoses, such as pancreatic cancer.
      While nonspecific, imaging findings which favor a diagnosis of AIP rather than
      pancreatic cancer include: delayed enhancement of affected pancreas, mild
      dilatation of the main pancreatic duct over a long segment, the "capsule" and
      "penetrating duct" signs, and responsiveness to corticosteroid therapy. Systemic,
      extra-pancreatic sites of involvement are also often seen in AIP and IgG4-related
      disease, and typically respond to corticosteroid therapy. Imaging by CT, MR, and
      PET also play a role in the diagnosis and monitoring after treatment of involved
      sites. 

PMID- 25386066
TI  - Intestinal microbiota in health and disease: role of bifidobacteria in gut
      homeostasis.
AB  - The pool of microbes inhabiting our body is known as "microbiota" and their
      collective genomes as "microbiome". The colon is the most densely populated organ
      in the human body, although other parts, such as the skin, vaginal mucosa, or
      respiratory tract, also harbour specific microbiota. This microbial community
      regulates some important metabolic and physiological functions of the host, and
      drives the maturation of the immune system in early life, contributing to its
      homeostasis during life. Alterations of the intestinal microbiota can occur by
      changes in composition (dysbiosis), function, or microbiota-host interactions and
      they can be directly correlated with several diseases. The only disease in which
      a clear causal role of a dysbiotic microbiota has been demonstrated is the case
      of Clostridium difficile infections. Nonetheless, alterations in composition and
      function of the microbiota have been associated with several gastrointestinal
      diseases (inflammatory bowel disease, colorectal cancer, or irritable bowel
      syndrome), as well as extra-intestinal pathologies, such as those affecting the
      liver, or the respiratory tract (e.g., allergy, bronchial asthma, and cystic
      fibrosis), among others. Species of Bifidobacterium genus are the normal
      inhabitants of a healthy human gut and alterations in number and composition of
      their populations is one of the most frequent features present in these diseases.
      The use of probiotics, including bifidobacteria strains, in preventive medicine
      to maintain a healthy intestinal function is well documented. Probiotics are also
      proposed as therapeutic agents for gastrointestinal disorders and other
      pathologies. The World Gastroenterology Organization recently published potential
      clinical applications for several probiotic formulations, in which species of
      lactobacilli are predominant. This review is focused on probiotic preparations
      containing Bifidobacterium strains, alone or in combination with other bacteria,
      which have been tested in human clinical studies. In spite of extensive
      literature on and research into this topic, the degree of scientific evidence of
      the effectiveness of probiotics is still insufficient in most cases. More effort
      need to be made to design and conduct accurate human studies demonstrating the
      efficacy of probiotics in the prevention, alleviation, or treatment of different
      pathologies. 

PMID- 25386068
TI  - Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis.
AB  - A large body of experimental and clinical data supports the notion that
      inflammation in acute pancreatitis has a crucial role in the pathogenesis of
      local and systemic damage and is a major determinant of clinical severity. Thus,
      research has recently focused on molecules that can regulate the inflammatory
      processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and
      protein kinases involved in intracellular signal transduction. Studies using
      genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in
      particular the class I PI3Kdelta and PI3Kgamma, have contributed to a greater
      understanding of the roles of these kinases in the modulation of inflammatory and
      immune responses. Recent data suggest that PI3Ks are also involved in the
      pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and
      in particular of the class IB PI3Kgamma isoform, has a significant role in those
      events which are necessary for the initiation of acute pancreatic injury, namely
      calcium signaling alteration, trypsinogen activation, and nuclear factor-kappaB
      transcription. Moreover, PI3Kgamma is instrumental in modulating acinar cell
      apoptosis, and regulating local neutrophil infiltration and systemic inflammatory
      responses during the course of experimental acute pancreatitis. The availability
      of PI3K inhibitors selective for specific isoforms may provide new valuable
      therapeutic strategies to improve the clinical course of this disease. This
      article presents a brief summary of PI3K structure and function, and highlights
      recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis. 

PMID- 25386071
TI  - Insulin resistance and liver steatosis in chronic hepatitis C infection genotype
      3.
AB  - Hepatitis C virus (HCV) infection is a common chronic liver disease worldwide.
      Non-alcoholic fatty liver disease and insulin resistance (IR) are the major
      determinants of fibrosis progression and response to antiviral therapy. The
      pathogenetic link between IR and chronic HCV infection is complex, and is
      associated with HCV genotype. Liver steatosis is the most common in the patients
      infected with genotype 3 virus, possibly due to direct effects of genotype 3
      viral proteins. To the contrary, hepatic steatosis in the patients infected with
      other genotypes is thought to be mostly due to the changes in host metabolism,
      involving IR. In HCV genotype 3, liver steatosis correlates with viral load,
      reverts after reaching the sustained virologic response and reoccurs in the
      relapsers. A therapeutic strategy to improve IR and liver steatosis and
      subsequently the response to antiviral treatment in these patients is warranted. 

PMID- 25386069
TI  - Immune-modulating therapy in acute pancreatitis: fact or fiction.
AB  - Acute pancreatitis (AP) is one of the most common diseases of the
      gastrointestinal tract, bearing significant morbidity and mortality worldwide.
      Current treatment of AP remains unspecific and supportive and is mainly targeted
      to aggressively prevent systemic complications and organ failure by intensive
      care. As acute pancreatitis shares an indistinguishable profile of inflammation
      with sepsis, therapeutic approaches have turned towards modulating the systemic
      inflammatory response. Targets, among others, have included pro- and anti
      inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules
      and platelets. Even though, initial results in experimental models have been
      encouraging, clinical implementation of immune-regulating therapies in acute
      pancreatitis has had a slow progress. Main reasons include difficulty in clinical
      translation of experimental data, poor understanding of inflammatory response
      time-course, flaws in experimental designs, need for multimodal approaches and
      commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a
      fact or just fiction remains to be seen in the future. 

PMID- 25386070
TI  - Heterogeneity across the murine small and large intestine.
AB  - The small and large intestine of the gastrointestinal tract (GIT) have evolved to
      have discrete functions with distinct anatomies and immune cell composition. The
      importance of these differences is underlined when considering that different
      pathogens have uniquely adapted to live in each region of the gut. Furthermore,
      different regions of the GIT are also associated with differences in
      susceptibility to diseases such as cancer and chronic inflammation. The large and
      small intestine, given their anatomical and functional differences, should be
      seen as two separate immunological sites. However, this distinction is often
      ignored with findings from one area of the GIT being inappropriately extrapolated
      to the other. Focussing largely on the murine small and large intestine, this
      review addresses the literature relating to the immunology and biology of the two
      sites, drawing comparisons between them and clarifying similarities and
      differences. We also highlight the gaps in our understanding and where further
      research is needed. 

PMID- 25386072
TI  - Gastrointestinal endoscopy in pregnancy.
AB  - Gastrointestinal endoscopy has a major diagnostic and therapeutic role in most
      gastrointestinal disorders; however, limited information is available about
      clinical efficacy and safety in pregnant patients. The major risks of endoscopy
      during pregnancy include potential harm to the fetus because of hypoxia,
      premature labor, trauma and teratogenesis. In some cases, endoscopic procedures
      may be postponed until after delivery. When emergency or urgent indications are
      present, endoscopic procedures may be considered with some precautions. United
      States Food and Drug Administration category B drugs may be used in low doses.
      Endoscopic procedures during pregnancy may include upper gastrointestinal
      endoscopy, percutaneous endoscopic gastrostomy, sigmoidoscopy, colonoscopy,
      enteroscopy of the small bowel or video capsule endoscopy, endoscopic retrograde
      cholangiopancreatography and endoscopic ultrasonography. All gastrointestinal
      endoscopic procedures in pregnant patients should be performed in hospitals by
      expert endoscopists and an obstetrician should be informed about all endoscopic
      procedures. The endoscopy and flexible sigmoidoscopy may be safe for the fetus
      and pregnant patient, and may be performed during pregnancy when strong
      indications are present. Colonoscopy for pregnant patients may be considered for
      strong indications during the second trimester. Although therapeutic endoscopic
      retrograde cholangiopancreatography may be considered during pregnancy, this
      procedure should be performed only for strong indications and attempts should be
      made to minimize radiation exposure. 

PMID- 25386073
TI  - Role of endoscopic retrograde cholangiopancreatography in the management of
      hepatic hydatid disease.
AB  - Most cases of hepatic hydatid disease exhibit uncomplicated clinical course and
      management. However, the diagnosis and management of complicated hepatic hydatid
      disease is a special issue. One of the most common and serious complications of
      hepatic hydatid disease is the rupture of the cyst into intrahepatic bile ducts.
      The clinical appearance of intrabiliary rupture can range from asymptomatic to
      jaundice, cholecystitis, cholangitis, liver abscess, pancreatitis and septicemia.
      Current treatments for major ruptures can result in high morbidity and mortality
      rates. Furthermore, ruptures that cannot be diagnosed preoperatively can induce
      complications such as biliary fistulae, biloma, cavitary infection and
      obstructive jaundice. In the past, these complications were diagnosed and treated
      by surgical methods. Currently, complications in both the pre- and postoperative
      periods are diagnosed and treated by non-invasive or minimally invasive methods.
      In clinical practice, endoscopic retrograde cholangiopancreatography (ERCP) is
      indicated for patients with preoperative frank intrabiliary rupture in which
      hydatid elements are clearly seen in the bile ducts, or for biliary adverse
      events after surgery, including persistent biliary fistulae and jaundice.
      However, controversy concerning routine preoperative ERCP and prophylactic
      endoscopic sphincterotomy in patients suspected of having minor cystobiliary
      communications still remains. In this article, the role of ERCP in the diagnosis
      and management of hepatic hydatid disease during the pre- and postoperative
      periods is reviewed. 

PMID- 25386074
TI  - Sexually transmitted infections of the anus and rectum.
AB  - Sexually transmitted infections (STIs) represent a significant public health
      concern. Several STIs, once thought to be on the verge of extinction, have
      recently reemerged. This change is thought to be partially related to an increase
      in STIs of the anus and rectum. Importantly, the global human immunodeficiency
      virus and acquired immunodeficiency syndrome (HIV/AIDS) epidemic has contributed
      to the emergence of particular anorectal lesions that require specialized
      approaches. In this report, we review common anorectal STIs that are frequently
      referred to colorectal surgeons in the United States. Epidemiology, clinical
      presentation, and management are summarized, including the latest treatment
      recommendations. The particularity of anorectal diseases in HIV/AIDS is
      addressed, along with recent trends in anal cytology and human papillomavirus
      vaccination. 

PMID- 25386075
TI  - Downregulation of signal transducer and activator of transcription 3 by
      sorafenib: a novel mechanism for hepatocellular carcinoma therapy.
AB  - Hepatocellular carcinoma is one of the most common cancers worldwide, and a
      leading cause of cancer-related death. Owing to unsatisfactory clinical outcomes
      under the current standard of care, there is a need to search for and identify
      novel and potent therapeutic targets to improve patient outcomes. Sorafenib is
      the first and only approved targeted therapy for the treatment of hepatocellular
      carcinoma. Besides functioning as a multiple tyrosine kinase, sorafenib also acts
      via a kinase-independent mechanism to target signal transducer and activator of
      transcription 3 (STAT3) signaling in hepatocellular carcinoma cells. STAT3 is a
      key regulator of inflammation, cell survival, and tumorigenesis of liver cells,
      and the high percentage of hepatocellular carcinoma cells with constitutively
      active STAT3 justifies targeting it for the development of novel therapeutics.
      Sorafenib inactivates STAT3 and STAT3-related signaling by inducing a
      conformational change in and releasing the autoinhibition of Src homology region
      2 domain-containing phosphatase-1. This phosphatase negatively regulates STAT3
      activity, which leads to the subsequent apoptosis of cancer cells. The novel anti
      cancer property of sorafenib will be discussed in this review, not only adding
      information regarding its mechanism of action but also providing an innovative
      approach for the development of cancer therapeutics in the future. 

PMID- 25386076
TI  - Differential control of growth, apoptotic activity and gene expression in human
      colon cancer cells by extracts derived from medicinal herbs, Rhazya stricta and
      Zingiber officinale and their combination.
AB  - AIM: To investigate the effects of extracts from Rhazya stricta (R. stricta) and
      Zingiber officinale (Z. officinale) on human colorectal cancer cells. METHODS:
      Human colorectal cancer cells (HCT116) were subjected to increasing doses of
      crude alkaloid extracts from R. stricta (CAERS) and crude flavonoid extracts from
      Z. officinale (CFEZO). Cells were then harvested after 24, 48 or 72 h and cell
      viability was examined by trypan blue exclusion dye test; clonogenicity and soft
      agar colony-forming assays were also carried out. Nuclear stain (Hoechst 33342),
      acridine orange/ethidium bromide double staining, agarose gel electrophoresis and
      comet assays were performed to assess pro-apoptotic potentiality of the extracts.
      Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using
      gene-specific primers and Western blot analyses were performed to assess the
      impact of CAERS and CFEZO on the expression levels of key regulatory proteins in
      HCT116 cells. RESULTS: Treatment with a combination of CAERS and CFEZO
      synergistically suppressed the proliferation, colony formation and anchorage
      independent growth of HCT116 cells. Calculated IC50, after 24, 48 and 72 h, were
      70, 90 and 130 MUg/mL for CAERS, 65, 85 and 120 MUg/mL for CFEZO and 20, 25 and
      45 MUg/mL for both agents, respectively. CAERS- and CFEZO-treated cells exhibited
      morphologic and biochemical features of apoptotic cell death. The induction of
      apoptosis was associated with the release of mitochondrial cytochrome c, an
      increase in the Bax/Bcl-2 ratio, activation of caspases 3 and 9 and cleavage of
      poly ADP-ribose polymerase. CAERS and CFEZO treatments downregulated expression
      levels of anti-apoptotic proteins including Bcl-2, Bcl-X, Mcl-1, survivin and
      XIAP, and upregulated expression levels of proapoptotic proteins such as Bad and
      Noxa. CAERS and CFEZO treatments elevated expression levels of the oncosuppressor
      proteins, p53, p21 and p27, and reduced levels of the oncoproteins, cyclin D1,
      cyclin/cyclin-dependent kinase-4 and c-Myc. CONCLUSION: These data suggest that a
      combination of CAERS and CFEZO is a promising treatment for the prevention of
      colon cancer.

PMID- 25386077
TI  - N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic
      reticulum stress during liver ischemia-reperfusion injury.
AB  - AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic
      reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury
      (IRI). METHODS: Mice were injected with NAC (300 mg/kg) intraperitoneally 2 h
      before ischemia. Real-time polymerase chain reaction and western blotting
      determined ER stress molecules (GRP78, ATF4 and CHOP). To analyze the role of NAC
      in reactive oxygen species (ROS)-mediated ER stress and apoptosis, lactate
      dehydrogenase (LDH) was examined in cultured hepatocytes treated by H2O2 or
      thapsigargin (TG). RESULTS: NAC treatment significantly reduced the level of ROS
      and attenuated ROS-induced liver injury after IRI, based on glutathione,
      malondialdehyde, serum alanine aminotransferase levels, and histopathology. ROS
      mediated ER stress was significantly inhibited in NAC-treated mice. In addition,
      NAC treatment significantly reduced caspase-3 activity and apoptosis after
      reperfusion, which correlated with the protein expression of Bcl-2 and Bcl-xl.
      Similarly, NAC treatment significantly inhibited LDH release from hepatocytes
      treated by H2O2 or TG. CONCLUSION: This study provides new evidence for the
      protective effects of NAC treatment on hepatocytes during IRI. Through inhibition
      of ROS-mediated ER stress, NAC may be critical to inhibit the ER-stress-related
      apoptosis pathway.

PMID- 25386078
TI  - Effects of baicalin in CD4 + CD29 + T cell subsets of ulcerative colitis
      patients.
AB  - AIM: To evaluate the role of baicalin in ulcerative colitis (UC) with regard to
      the CD4(+)CD29(+) T helper cell, its surface markers and serum inflammatory
      cytokines. METHODS: Flow cytometry was used to detect the percentage of
      CD4(+)CD29(+) cells in patients with UC. Real time polymerase chain reaction was
      used to detect expression of GATA-3, forkhead box P3, T-box expressed in T cells
      (T-bet), and retinoic acid-related orphan nuclear hormone receptor C (RORC).
      Western blotting was used to analyze expression of nuclear factor-kappaB (NF
      kappaB) p65, phosphorylation of NF-kappaB (p-NF-kappaB) p65, STAT4, p-STAT4,
      STAT6 and p-STAT6. The concentrations of interferon-gamma (IFN-gamma),
      interleukin (IL)-4, IL-5, IL-6, IL-10 and TGF-beta in serum were determined by
      ELISA assay. RESULTS: The percentages of CD4(+)CD29(+) T cells were lower in
      treatment with 40 and 20 MUmol/L baicalin than in the treatment of no baicalin.
      Treatment with 40 or 20 MUmol/L baicalin significantly upregulated expression of
      IL-4, TGF-beta1 and IL-10, increased p-STAT6/STAT6 ratio, but downregulated
      expression of IFN-gamma, IL-5, IL-6, RORC, Foxp3 and T-bet, and decreased ratios
      of T-bet/GATA-3, p-STAT4/STAT4 and p-NF-kappaB/NF-kappaB compared to the
      treatment of no baicalin. CONCLUSION: The results indicate that baicalin
      regulates immune balance and relieves the ulcerative colitis-induced inflammation
      reaction by promoting proliferation of CD4(+)CD29(+) cells and modulating
      immunosuppressive pathways.

PMID- 25386079
TI  - Therapeutic effect of a hydroxynaphthoquinone fraction on dextran sulfate sodium
      induced ulcerative colitis.
AB  - AIM: To evaluate the therapeutic effect of hydroxynaphthoquinone mixture (HM) on
      dextran sulfate sodium (DSS)-induced colitis and explore the underlying
      mechanisms. METHODS: BALB/c mice received 3.5% DSS for 6 d to induce ulcerative
      colitis. Groups of mice were orally administered HM 3.5, 7 and 14 mg/kg and
      mesalazine 200 mg/kg per day for 7 d. During the experiment, clinical signs and
      body weight, stool consistency and visible fecal blood were monitored and
      recorded daily. A disease activity index score was calculated for each animal. At
      the conclusion of the experiment, the colonic histopathological lesions were
      evaluated. Myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF
      alpha) levels were determined. Protein expression levels of TNF-alpha, nuclear
      factor-kappaB (NF-kappaB) p65, inhibitor of kappaB (IkappaB) and phosphorylation
      of IkappaB (p-IkappaB) were analyzed by Western blot analysis. RESULTS:
      Administration of 3.5% DSS for 6 d successfully induced acute colitis associated
      with soft stool, diarrhea, rectal bleeding, and colon shortening, as well as a
      loss of body weight. Administration of HM effectively attenuated the severity of
      colonic mucosa injury. For histopathological analysis, HM treatment improved
      histological alterations and lowered pathological scores compared with the DSS
      only group. This manifested as a reduction in the extent of colon injury and
      inflammatory cell infiltration, as well as the degree of mucosal destruction. In
      addition, HM at doses of 7 and 14 mg/kg significantly decreased MPO activity in
      colonic tissue (0.98 +/- 0.22 U/g vs 1.32 +/- 0.24 U/g, 0.89 +/- 0.37 U/g vs 1.32
      +/- 0.24 U/g tissue, P < 0.05) and serum TNF-alpha levels (68.78 +/- 7.34 ng/L vs
      88.98 +/- 17.79 ng/L, 64.13 +/- 14.13 ng/L vs 88.98 +/- 17.79 ng/L, P < 0.05).
      Furthermore, HM down-regulated the expression of TNF-alpha, NF-kappaB p65 and p
      IkappaBalpha in colonic tissue while up-regulating IkappaBalpha protein
      expression. These results suggest that the significant anti-inflammatory effect
      of HM may be attributable to its inhibition of TNF-alpha production and NF-kappaB
      activation. CONCLUSION: HM had a favorable therapeutic effect on DSS-induced
      ulcerative colitis, supporting its further development and clinical application
      in inflammatory bowel disease.

PMID- 25386080
TI  - Beneficial effects of adenosine triphosphate-sensitive K+ channel opener on liver
      ischemia/reperfusion injury.
AB  - AIM: To investigate the effect of diazoxide administration on liver
      ischemia/reperfusion injury. METHODS: Wistar male rats underwent partial liver
      ischemia performed by clamping the pedicle from the medium and left anterior
      lateral segments for 1 h under mechanical ventilation. They were divided into 3
      groups: Control Group, rats submitted to liver manipulation, Saline Group, rats
      received saline, and Diazoxide Group, rats received intravenous injection
      diazoxide (3.5 mg/kg) 15 min before liver reperfusion. 4 h and 24 h after
      reperfusion, blood was collected for determination of aspartate transaminase
      (AST), alanine transaminase (ALT), tumor necrosis factor (TNF-alpha), interleukin
      6 (IL-6), interleukin-10 (IL-10), nitrite/nitrate, creatinine and tumor growth
      factor-beta1 (TGF-beta1). Liver tissues were assembled for mitochondrial
      oxidation and phosphorylation, malondialdehyde (MDA) content, and histologic
      analysis. Pulmonary vascular permeability and myeloperoxidase (MPO) were also
      determined. RESULTS: Four hours after reperfusion the diazoxide group presented
      with significant reduction of AST (2009 +/- 257 U/L vs 3523 +/- 424 U/L, P =
      0.005); ALT (1794 +/- 295 U/L vs 3316 +/- 413 U/L, P = 0.005); TNF-alpha (17 +/-
      9 pg/mL vs 152 +/- 43 pg/mL, P = 0.013; IL-6 (62 +/- 18 pg/mL vs 281 +/- 92
      pg/mL); IL-10 (40 +/- 9 pg/mL vs 78 +/- 10 pg/mL P = 0.03), and nitrite/nitrate
      (3.8 +/- 0.9 MUmol/L vs 10.2 +/- 2.4 MUmol/L, P = 0.025) when compared to the
      saline group. A significant reduction in liver mitochondrial dysfunction was
      observed in the diazoxide group compared to the saline group (P < 0.05). No
      differences in liver MDA content, serum creatinine, pulmonary vascular
      permeability and MPO activity were observed between groups. Twenty four hours
      after reperfusion the diazoxide group showed a reduction of AST (495 +/- 78 U/L
      vs 978 +/- 192 U/L, P = 0.032); ALT (335 +/- 59 U/L vs 742 +/- 182 U/L, P =
      0.048), and TGF-beta1 (11 +/- 1 ng/mL vs 17 +/- 0.5 ng/mL, P = 0.004) serum
      levels when compared to the saline group. The control group did not present
      alterations when compared to the diazoxide and saline groups. CONCLUSION:
      Diazoxide maintains liver mitochondrial function, increases liver tolerance to
      ischemia/reperfusion injury, and reduces the systemic inflammatory response.
      These effects require further evaluation for using in a clinical setting.

PMID- 25386081
TI  - Intestinal ischemia-reperfusion of macaques triggers a strong innate immune
      response.
AB  - AIM: To investigate inflammatory injury in the intestinal mucosa after intestinal
      ischemia-reperfusion (IIR) with Toll-like receptor (TLR)-mediated innate
      immunity. METHODS: Ten macaques were randomized into control and IIR groups. The
      distribution and expression level of TLR2, TLR4, MD2, nuclear factor (NF)-kappaB
      p65 and interferon (IFN)-gamma were measured by immunohistochemical stain and
      western blotting. The mRNA expression of TLR4, TLR2, MD2, interleukin (IL)-1beta
      and tumor necrosis factor (TNF)-alpha were measured by reverse transcriptase
      polymerase chain reaction. The cytokine levels in blood and intestinal tissues
      were measured by ELISA. RESULTS: Obvious hemorrhage and erosion of mucosae were
      seen in the IIR group. Expression of TLR2, TLR4, MD2, NF-kappaB p65 and IFN-gamma
      was significantly higher in the IIR group than in the control group (0.13 +/-
      0.04, 0.22 +/- 0.04, 0.16 +/- 0.06, 0.65 +/- 0.12, 0.38 +/- 0.10 vs 0.07 +/-
      0.04, 0.08 +/- 0.03, 0.04 +/- 0.02, 0.19 +/- 0.06, 0.14 +/- 0.05, P < 0.05). In
      addition, the expression of TLR2, TLR4, MD2, IL-1beta and TNF-alpha mRNA in the
      IIR group were significantly higher than those of control group(1.52 +/- 0.15,
      1.39 +/- 0.06, 1.94 +/- 0.12, 1.48 +/- 0.15, 0.66 +/- 0.08 vs 0.31 +/- 0.05, 0.5
      +/- 0.04, 0.77 +/- 0.05, 0.35 +/- 0.08, 0.18 +/- 0.04, P < 0.05). Furthermore, IL
      1beta, IL-6 and TNF-alpha levels in the macaques ileum and plasma were
      significantly higher than in the control group (plasma: 86.3 +/- 15.2, 1129 +/-
      248.3, 77.8 +/- 16.2 vs 29.5 +/- 7.3, 19.8 +/- 8.2, 5.6 +/- 1.7; ileum: 273.4. +/
      44.7, 1636 +/- 168.0, 205.5 +/- 30.7 vs 76.8 +/- 20.5, 663.4 +/- 186.9, 49.0 +/-
      9.4; P < 0.05). CONCLUSION: After IIR, general inflammatory injury in the
      intestinal mucosa is correlated with a strong innate immune response, mediated by
      activation of the TLR-NF-kappaB-cytokine pathway.

PMID- 25386082
TI  - Resveratrol and genistein inhibition of rat isolated gastrointestinal
      contractions and related mechanisms.
AB  - AIM: To investigate the effects and underlying mechanisms of resveratrol and
      genistein on contractile responses of rat gastrointestinal smooth muscle.
      METHODS: Isolated strips of gastrointestinal smooth muscle from Spraque-Dawley
      rats were suspended in organ baths containing Kreb's solution, and the
      contractility of smooth muscles was measured before and after incubation with
      resveratrol and genistein, and the related mechanisms were studied by co
      incubation with various inhibitors. RESULTS: Resveratrol and genistein dose
      dependently decreased the resting tension, and also reduced the mean contractile
      amplitude of gastrointestinal smooth muscle. Estrogen receptor blockades (ICI
      182780 and tamoxifen) failed to alter the inhibitory effects induced by
      resveratrol and genistein. However, their effects were attenuated by inhibitions
      of alpha-adrenergic receptor (phentolamine), nitric oxide synthase (levorotatory
      NG-nitroarginine), ATP-sensitive potassium channels (glibenclamide), and cyclic
      adenosine monophosphate (SQ22536). In high K(+)/Ca(2+)-free Kreb's solution
      containing 0.01 mmol/L egtazic acid, resveratrol and genistein reduced the
      contractile responses of CaCl2, and shifted its cumulative concentration-response
      curves rightward. CONCLUSION: Resveratrol and genistein relax gastrointestinal
      smooth muscle via alpha-adrenergic receptors, nitric oxide and cyclic adenosine
      monophosphate pathways, ATP-sensitive potassium channels, and inhibition of L
      type Ca(2+) channels.

PMID- 25386083
TI  - Elevated miR-33a and miR-224 in steatotic chronic hepatitis C liver biopsies.
AB  - AIM: To assess the expression of selected microRNAs (miRNA) in hepatitis C,
      steatotic hepatitis C, noninfected steatotic and normal liver tissues. METHODS:
      The relative expression levels of miR-21, miR-33a, miR-96, miR-122, miR-125b, miR
      221 and miR-224 were determined in 76 RNA samples isolated from 18 non-steatotic
      and 28 steatotic chronic hepatitis C (CHC and CHC-Steatosis, respectively) cases,
      18 non-infected, steatotic liver biopsies of metabolic origin (Steatosis) and 12
      normal formalin-fixed paraffin-embedded liver tissues using TaqMan MicroRNA
      Assays. All CHC biopsy samples were obtained prior to initiating therapy.
      Patients' serum biochemical values, which included glucose, triglyceride,
      cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      gamma-glutamyl-transferase (GGT), alkaline phosphatase (AP), were obtained and
      correlated with relative miRNA expression. RESULTS: When compared with control
      non-infected liver samples, miR-122 and miR-221 levels were reduced in CHC
      Steatosis (P < 0.03) and in CHC, CHC-Steatosis and Steatosis (P < 0.01).
      Alternatively, the expression of miR-33a and miR-224 were elevated in CHC
      Steatosis and Steatosis in comparison to control tissue (P < 0.01). The levels of
      miR-33a and miR-224 in CHC-Steatosis (P < 0.02) and miR-224 in Steatosis (P <
      0.001) were increased in comparison to CHC samples. By contrast, the expression
      of miR-21 did not differ statistically between diseased and normal liver samples.
      Levels of miR-33a correlated negatively with serum AST and AP levels in Steatosis
      as well as with necroinflammatory grade in CHC, whereas miR-21 correlated
      positively with AST in Steatosis and displayed negative correlation with
      triglyceride level in CHC-Steatosis. In contrast, miRNA levels were not
      correlated with ALT, GGT, cholesterol levels or fibrosis stage. CONCLUSION:
      Differences in miRNA expression were observed between CHC and steatotic CHC, CHC
      and steatotic liver, but not between steatotic CHC and steatotic liver of
      metabolic origin.

PMID- 25386084
TI  - Resistin is not an appropriate biochemical marker to predict severity of acute
      pancreatitis: a case-controlled study.
AB  - AIM: To assess levels of serum resistin upon hospital admission as a predictor of
      acute pancreatitis (AP) severity. METHODS: AP is both a common and serious
      disease, with severe cases resulting in a high mortality rate. Several predictive
      inflammatory markers have been used clinically to assess severity. This
      prospective study collected data from 102 patients who were diagnosed with an
      initial acute biliary pancreatitis between March 2010 and February 2013.
      Measurements of body mass index (BMI) and waist circumference (WC) were obtained
      and serum resistin levels were analyzed at the time of hospital admission using
      enzyme-linked immunosorbent assay. Additionally, resistin levels were measured
      from a control group after matching gender, BMI and age. RESULTS: A total of 102
      patients (60 females and 42 males) were diagnosed with acute gallstone-induced
      pancreatitis. The mean age was 45 years, and mean BMI value was 30.5 kg/m(2)
      (Obese, class I). Twenty-two patients (21.6%) had severe AP, while eighty-eight
      patients had mild pancreatitis (78.4%). Our results showed that BMI significantly
      correlated with pancreatitis severity (P = 0.007). Serum resistin did not
      correlate with BMI, weight or WC. Furthermore, serum resistin was significantly
      higher in patients with AP compared to control subjects (P < 0.0001). The mean
      resistin values upon admission were 17.5 ng/mL in the severe acute biliary
      pancreatitis group and 16.82 ng/mL in the mild AP group (P = 0.188), indicating
      that resistin is not an appropriate predictive marker of clinical severity.
      CONCLUSION: We demonstrate that obesity is a risk factor for developing severe
      AP. Further, although there is a correlation between serum resistin levels and AP
      at the time of hospital admission, resistin does not adequately serve as a
      predictive marker of clinical severity.

PMID- 25386085
TI  - Hepatitis B vaccination in patients with inflammatory bowel disease.
AB  - AIM: To determine the prevalence for hepatitis B virus (HBV) and HBV screening
      and vaccination practices for inflammatory bowel disease (IBD). METHODS: This
      study is a retrospective, cross-sectional observational study. A retrospective
      chart review was performed in 500 patients who have been consecutively treated
      for IBD between September 2008 and January 2013 at the Rush University Medical
      Center Gastroenterology section. The patients were identified through the
      electronic medical record with the criteria that they attended the
      gastroenterology clinic, and that they had a diagnosis of IBD at the time of
      visit discharge. Once identified, each record was analyzed to determine whether
      the subject had been infected with HBV in the past, already been vaccinated
      against HBV, or advised to get vaccinated and followed through with the
      recommended vaccination. RESULTS: About 254 out of 500 patients (51%) had HBV
      screening ordered. Among those ordered to have screening tests, 86% followed
      through with HBV serology. Gastroenterology physicians had significantly
      different screening ratios from each other (P < 0.001). There were no significant
      differences in the ratios of HBV screening when IBD specialists were compared to
      other gastroenterology physicians (0.505 +/- 0.023 vs 0.536 +/- 0.066, P = 0.66).
      Of those 220 patients screened, 51% of IBD patients were found not to be immune
      against HBV. Approximately 50% of gastroenterology physicians recommended HBV
      vaccinations to their patients in whom serology was negative for antibodies
      against HBV. IBD specialists recommended vaccinations to a higher percentage of
      their patients compared to other gastroenterology physicians (0.168 +/- 0.019 vs
      0.038 +/- 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6%
      of the patients who had serology checked. There was no statistically significant
      difference in the prevalence of hepatitis B surface antigen (HBsAg) between our
      study and that reported in previous studies done in Spain (4/220 vs 14/2076
      respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159).
      But, the prevalence of anti-HBcAb in this study was less than that reported in
      the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not
      significantly different from that reported in the study in France (7/220 vs 8/315
      respectively, P = 0.313). CONCLUSION: The prevalence of HBsAg in our IBD patients
      was not higher than previously reported European studies. Most IBD patients are
      not routinely screened or vaccinated against HBV at a tertiary referral center in
      the United States.

PMID- 25386086
TI  - New strategies for prevention and treatment of splenic artery steal syndrome
      after liver transplantation.
AB  - AIM: To explore a prophylactic procedure to prevent splenic artery steal syndrome
      (SASS), as well as a therapeutic intervention to correct it. METHODS: Forty-three
      liver transplant patients were enrolled in a non-randomized controlled trial,
      with the eligible criterion that the diameter of the splenic artery is more than
      5 mm and/or 1.5 times of the diameter of the hepatic artery. The procedure of
      splenic artery banding was performed in 28 of the 43 patients, with the other 15
      patients studied as a control group. SASS and other complications were compared
      between these two groups. A new therapeutic intervention, temporary incomplete
      blockade of the splenic artery with a balloon, was performed to treat SASS in
      this study. RESULTS: The incidence of SASS was decreased by banding the splenic
      artery (0/28 vs 5/15, P = 0.006), and the same result was observed in total
      complications associated with prophylactic procedures (2/28 vs 6/15, P = 0.014).
      Five patients in the control group developed SASS within 5 d after OLT, 2 of whom
      were treated by coil embolization of the splenic artery, whereas the other 3 by
      temporary blockade of the splenic artery. Reappeared or better hepatic arteries
      with improved systolic amplitude and increased diastolic flow were detected by
      Doppler ultrasonography in all the 5 patients. Local splenic ischemic necrosis
      and nonanastomotic biliary stricture were diagnosed respectively in one patient
      treated by coil embolization, and no collateral complication was detected in
      patients treated by temporary blockade of the splenic artery. CONCLUSION: SASS
      should be avoided during the operation by banding the splenic artery. Temporary
      blockade of the splenic artery is a new safe and effective intervention for SASS.

PMID- 25386087
TI  - Performance of the Montreal classification for inflammatory bowel diseases.
AB  - AIM: To validate the Montreal classification system for Crohn's disease (CD) and
      ulcerative colitis (UC) within the Netherlands. METHODS: A selection of 20 de
      identified medical records with an appropriate representation of the inflammatory
      bowel disease (IBD) sub phenotypes were scored by 30 observers with different
      professions (gastroenterologist specialist in IBD, gastroenterologist in training
      and IBD-nurses) and experience level with IBD patient care. Patients were
      classified according to the Montreal classification. In addition, participants
      were asked to score extra-intestinal manifestations (EIM) and disease severity in
      CD based on their clinical judgment. The inter-observer agreement was calculated
      by percentages of correct answers (answers identical to the "expert evaluation")
      and Fleiss-kappa (kappa). Kappa cut-offs: < 0.4-poor; 0.41-0.6-moderate; 0.61-0.8
      good; > 0.8 excellent. RESULTS: The inter-observer agreement was excellent for
      diagnosis (kappa = 0.96), perianal disease (kappa = 0.92) and disease location in
      CD (kappa = 0.82) and good for age of onset (kappa = 0.67), upper
      gastrointestinal disease (kappa = 0.62), disease behaviour in CD (kappa = 0.79)
      and disease extent in UC (kappa = 0.65). Disease severity in UC was scored poor
      (kappa = 0.23). The additional items resulted in a good inter-observer agreement
      for EIM (kappa = 0.68) and a moderate agreement for disease severity in CD (kappa
      = 0.44). Percentages of correct answers over all Montreal items give a good
      reflection of the inter-observer agreement (> 80%), except for disease severity
      (48%-74%). IBD-nurses were significantly worse in scoring upper gastrointestinal
      disease in CD compared to gastroenterologists (P = 0.008) and gastroenterologists
      in training (P = 0.040). Observers with less than 10 years of experience were
      significantly better at scoring UC severity than observers with 10-20 years (P =
      0.003) and more than 20 years (P = 0.003) of experience with IBD patient care.
      Observers with 10-20 years of experience with IBD patient care were significantly
      better at scoring upper gastrointestinal disease in CD than observers with less
      than 10 years (P = 0.007) and more than 20 years (P = 0.007) of experience with
      IBD patient care. CONCLUSION: We found a good to excellent inter-observer
      agreement for all Montreal items except for disease severity in UC (poor).

PMID- 25386088
TI  - Same-day colonoscopy preparation with Senna alkaloids and bisacodyl tablets: a
      pilot study.
AB  - AIM: To evaluate the efficacy of same-day bowel preparation with Senna alkaloids
      combined with bisacodyl tablets in routine colonoscopy procedures. METHODS:
      Between March and June 2013, a same-day bowel preparation was implemented in our
      endoscopy unit. The preparation consisted of a semi-liquid, fiber-free diet one
      day prior to the procedure, with two bisacodyl tablets after lunch and dinner,
      and 250 mL of Senna alkaloid with 1.5 L of drinking water at 6 am the day of the
      procedure. The quality control parameters of colonoscopy were evaluated and
      implemented according to the guidelines of the American Society for
      Gastrointestinal Endoscopy. The pre-procedure, during-procedure and post
      procedure patient data were collected and analyzed: (1) pre-procedure (age,
      gender, comorbid diseases, colonoscopy indications, complete lack of compliance
      with the bowel preparation protocol); (2) during-procedure (sedation dose,
      duration of colonoscopy, withdrawal time, cecal intubation rate, polyp detection
      rate, Boston Bowel Preparation Scores and presence of foam and clear liquid); and
      (3) post-procedure (visual analogue scale score, pain during the procedure,
      patient satisfaction and premature withdrawal due to the insufficient bowel
      preparation). RESULTS: A total of 75 patients were included in this study with a
      mean age of 54.64 +/- 13.29 years; 53.3% (40/75) were female and 46.7% (35/75)
      were male. A complete lack of compliance with the bowel preparation protocol was
      seen in 6.7% of patients (5/75). The mean total duration of colonoscopy was 16.12
      +/- 6.51 min, and the mean withdrawal time was 8.89 +/- 4.07 min. The cecal
      intubation rate was 93.8% (61/64) and the polyp detection rate was 40% (30/75).
      The mean Boston Bowel Preparation Score was 7.38 +/- 1.81, with the following
      distribution: right colon, 2.34 +/- 0.89; transverse colon, 2.52 +/- 0.67; left
      colon, 2.52 +/- 0.63. The mean visual analogue scale score was 4.59 +/- 1.57. Due
      to insufficient bowel preparation, seven patients (7/75; 9.3%) were asked to
      repeat the procedure. Of these, five patients had poor or modest compliance with
      the protocol, and two patients reported constipation. Premature withdrawal due to
      insufficient bowel preparation was 2.7% (2/75). The overall satisfaction with the
      protocol was 86.7% (65/75), with patients reporting they would prefer the same
      protocol in a repeat procedure. CONCLUSION: The same-day administration of Senna
      alkaloids appears to be a safe and effective bowel cleansing protocol for
      colonoscopy procedures.

PMID- 25386089
TI  - Effect of spleen operation on antiviral treatment in hepatitis C virus-related
      cirrhotic patients.
AB  - AIM: To investigate the impact of spleen operation (SO) on interferon-alpha (IFN
      alpha)-based antiviral treatment in patients with hepatitis C virus (HCV)-related
      cirrhosis. METHODS: Studies were systematically identified by searching
      electronic databases including MEDLINE, Cochrane Library, Elsevier, and Embase up
      to September 30, 2013, and relevant clinical studies were reviewed. Sustained
      virological response (SVR) rate and adherence to therapy were taken as the
      endpoints of interest. RESULTS: A total of 603 patients from 16 studies were
      included in the systematic review. Of 372 patients who underwent SO followed by
      antiviral treatment, the total SVR rate was 39.5%. SVR was associated with HCV
      genotypes 2/3 (OR = 10.84; 95%CI: 5.47-21.47; P < 0.00001). IFN-alpha dose needed
      to be reduced in 29.4%, and IFN-alpha-based therapy was discontinued in 11.5% of
      patients. Analysis of controlled studies showed that SVRs were achieved in 34.1%
      of patients with SO and 31.1% of patients without SO. SO had no effect on the SVR
      rate in cirrhotic patients with genotype 1 HCV infection (OR = 1.28; 95%CI: 0.51
      3.22; P = 0.60), but improved the SVR rate in patients with genotypes 2/3
      infection, though the difference was not significant (OR = 0.36; 95%CI: 0.13
      1.02; P = 0.05). CONCLUSION: SO combined with IFN-alpha-based antiviral therapy
      may be suitable in cirrhotic patients with genotypes 2/3 HCV infection, but not
      in those with genotype 1 infection.

PMID- 25386090
TI  - Fish consumption and risk of gastrointestinal cancers: a meta-analysis of cohort
      studies.
AB  - AIM: To assess quantitatively the relationship between fish intake and the
      incidence of gastrointestinal cancers in a meta-analysis of cohort studies.
      METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, and the
      bibliographies of retrieved articles. Prospective cohort studies were included if
      they reported relative risks (RRs) and corresponding 95% confidence intervals
      (CIs) of various cancers with respect to fish intake. When RRs were not available
      in the published article, they were computed from the exposure distributions. Two
      investigators extracted the data independently and discrepancies were resolved by
      discussion with a third investigator. We performed random-effect meta-analyses
      and meta-regressions of study-specific incremental estimates to determine the
      risk of cancer associated with a 20-g/d increment of fish consumption. RESULTS:
      Forty-two studies, comprising 27 independent cohorts, met our inclusion criteria.
      The studies included 2325040 participants and 24115 incident cases of
      gastrointestinal cancer, with an average follow-up of 13.6 years. Compared with
      individuals who did not eat, or seldom ate, fish, the pooled RR of
      gastrointestinal cancers was 0.93 (95%CI: 0.88-0.98) for regular fish consumers,
      0.94 (0.89-0.99) for low to moderate fish consumers, and 0.91 (0.84-0.97) for
      high fish consumers. Overall, a 20-g increase in fish consumption per day was
      associated with a 2% reduced risk of gastrointestinal cancers (RR = 0.98; 95%CI:
      0.96-1.01). In subgroup analyses, we noted that fish consumption was associated
      with reduced risk of colorectal (RR = 0.93; 95%CI: 0.87-0.99; P < 0.01),
      esophageal (RR = 0.91; 95%CI: 0.83-0.99; P < 0.05) and hepatocellular cancers (RR
      = 0.71; 95%CI: 0.48-0.95; P < 0.01). CONCLUSION: This meta-analysis suggested
      that fish consumption may reduce total gastrointestinal cancer incidence. Inverse
      relationships were also detected between fish consumption and specific types of
      cancers.

PMID- 25386091
TI  - Consumption of garlic and risk of colorectal cancer: an updated meta-analysis of
      prospective studies.
AB  - AIM: To conduct an updated meta-analysis of prospective studies addressing the
      association between garlic consumption and colorectal cancer. METHODS: Eligible
      cohort studies were identified by searching MEDLINE (PubMed) and screening the
      references of related articles published up to October 2013. Meta-analyses were
      conducted for colorectal cancer in relation to consumption of raw and cooked (RC)
      garlic and garlic supplements, separately. The summary relative risks (RR) with
      95%CI were calculated using fixed-effects or random-effects model depending on
      the heterogeneity among studies. RESULTS: A total of 5 prospective cohort studies
      were identified. In contrast to the previous meta-analysis, no significant
      associations were found between consumption of RC garlic (RR: 1.06; 95%CI: 0.95
      1.19) or garlic supplements (RR: 1.12; 95%CI: 0.96-1.31) and risk of colorectal
      cancer. A non-significant protective effect of garlic supplement intake against
      colorectal cancer was observed in females (RR: 0.84; 95%CI: 0.64-1.11), but the
      opposite was the case in males (RR: 1.24; 95%CI: 0.96-1.59). CONCLUSION:
      Consumption of RC garlic or garlic supplements is not significantly associated
      with reduced colorectal cancer risk.

PMID- 25386092
TI  - Safety of fast-track rehabilitation after gastrointestinal surgery: systematic
      review and meta-analysis.
AB  - AIM: To compare the safety of fast-track rehabilitation protocols (FT) and
      conventional care strategies (CC), or FT and laparoscopic surgery (LFT) and FT
      and open surgery (OFT) after gastrointestinal surgery. METHODS: We searched
      MEDLINE, WHO International Trial Register, Embase and The Cochrane Central
      Register of Controlled Trials up to 2014 for randomized controlled trials (RCTs)
      comparing FT and CC or comparing LFT and OFT, with 10 or more randomized
      participants and about 30 d follow-up. Two reviewers independently extracted data
      on complications, anastomotic leak, obstruction, wound infection, re-admission
      between FT and CC or LFT and OFT after gastrointestinal surgery. RESULTS: Twenty
      four RCTs of FT vs CC or LFT vs OFT were included. Compared with CC, FT reduced
      overall complications and wound infection. However, anastomotic leak, obstruction
      and re-admission were not significantly reduced. The pooled risk ratio (RR) of
      0.69 (95%CI: 0.60-0.78; P < 0.001), pooled RR of 0.71 (95%CI: 0.57-0.88; P <
      0.001), pooled RR of 0.93 (95%CI: 0.68-1.25; P > 0.05), a pooled RR of 0.87
      (95%CI: 0.67-1.15; P > 0.05) and pooled RR of 0.94 (95%CI: 0.73-1.22; P > 0.05)
      respectively. Compared with OFT, LFT reduced complications, with a pooled RR of
      0.66 (95%CI: 0.54-0.81; P < 0.001). CONCLUSION: FTs are safe after
      gastrointestinal surgery. Additional large, prospective RCTs should be conducted
      to establish further the safety of this approach.

PMID- 25386093
TI  - MiR-146a rs2910164 polymorphism increases risk of gastric cancer: a meta
      analysis.
AB  - AIM: To systematically evaluate the association between the miR-146a rs2910164
      polymorphism and susceptibility to gastric cancer. METHODS: A comprehensive
      electronic search was conducted for articles published up until January 27, 2014
      in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and
      Google Scholar. Only case-control studies published in English that evaluated the
      association between the miR-146a rs2910164 polymorphism and susceptibility to
      gastric cancer were included. Furthermore, only studies with sufficient data
      allowing for calculation of odds ratio (OR) and corresponding 95% confidence
      interval (CI) were included. These values were used in the quantitative synthesis
      to assess the strength of the association between the miR-146a rs2910164
      polymorphism and risk of gastric cancer. RESULTS: The database search identified
      1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls)
      were included for the meta-analysis. The results indicate that miR-146a rs2910164
      polymorphism is more likely to be associated with gastric cancer risk. In the
      overall analysis, a significantly increased cancer risk was found in the
      heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for
      pooled OR). In the ethnicity subgroup analysis, a similar result was found among
      Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the
      stratified analysis by quality of studies, a significantly increased cancer risk
      was found in the heterozygote comparison among high quality studies (OR = 1.12,
      95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample
      size, a significantly increased cancer risk was found among small sample size
      subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01),
      homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model
      (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons. CONCLUSION:
      The miR-146a rs2910164 polymorphism is associated with increased gastric cancer
      risk, particularly evident in high quality studies with small sample sized
      Caucasian populations.

PMID- 25386094
TI  - Benign giant-cell tumor of the common bile duct: a case report.
AB  - Primary giant-cell tumors rarely arise in the common bile duct. We herein report
      a case of primary giant-cell tumor of the common bile duct. The patient was an 81
      year-old male who was diagnosed with a well-defined 1.2-cm mass projecting into
      the lumen of the middle common bile duct. Excision of the gallbladder and
      extrahepatic bile duct and a Roux-en-Y cholangiojejunostomy were performed.
      Histologically, the tumor had no association with carcinomas of epithelial origin
      and was similar to giant-cell tumors of the bone. The tumor consisted of a
      mixture of mononuclear and multinucleated osteoclast-like giant cells. The
      mononuclear cells showed no atypical features, and their nuclei were similar to
      those of the multinucleated giant cells. CD68 was expressed on the mononuclear
      and multinucleated osteoclast-like giant cells, whereas CD163 immunoreactivity
      was restricted to the mononuclear cells. Six months after the operation, the
      patient was still alive and had no recurrence. The interest of this case lies in
      the rarity of this entity, the difficulty of preoperative diagnosis, and this
      tumor's possible confusion with other malignant tumors. 

PMID- 25386095
TI  - Malignant gangliocytic paraganglioma of the duodenum with distant metastases and
      a lethal course.
AB  - Gangliocytic paraganglioma (GP) is rare and has been regarded as benign in
      general with a good prognosis. We present a patient with duodenal GP showing a
      malignant and lethal clinical course. A 47-year-old male patient was found to
      have a duodenal tumor and enlarged regional lymph nodes. The patient initially
      underwent a pancreaticoduodenectomy to resect the tumor and involved lymph nodes
      completely. Histological and immunohistochemical analyses showed findings typical
      of GP. However, the distant metastatic lesions in the liver and pelvic cavity
      were rapidly observed after surgery. The patient underwent chemotherapy and
      radiotherapy, as well as a second surgery to partly remove the metastatic mass in
      the pelvic cavity. The histological examination revealed no significant
      difference in histological features between the primary duodenal tumor and the
      metastatic pelvic mass. However, the patient finally died of the tumor due to the
      recurrence of the residual pelvic lesion and increased liver mass. To our
      knowledge, this is the first report of lethal GP with multifocal metastases. Our
      case confirms that GP should be regarded as a malignant potential tumor with
      behavior code of "1", rather than a benign tumor of "0". 

PMID- 25386097
TI  - Late Complications following Endoscopic Sphincterotomy for Choledocholithiasis: A
      Swedish Population-Based Study.
AB  - In order to assess the risk of long-term complications following endoscopic
      sphincterotomy (ES) for common bile duct stones (CBDS), we conducted a cohort
      study. The study included 1,113 patients who underwent ES for CBDS in six
      different hospitals in central Sweden between 1977 and 1990. Through the use of
      the Swedish population registry, each patient was assigned five population-based
      controls matched for sex and age. Linkage to the Inpatient Registry yielded
      information on morbidity and mortality for the patients as well as for the
      controls. After one year of washout, there were 964 patients available for follow
      up. The mean age was 70.6 years, 57% were women, and the mean length of follow-up
      was 8.9 years. The patients' overall morbidity was significantly higher and we
      observed a tendency towards increased mortality as well. Recurrent CBDS was
      diagnosed in 4.1% of the patients. Acute cholangitis with a hazard ratio (HR) of
      36 (95%CI 11-119.4) was associated with recurrent CBDS in 39% of the patients. HR
      for acute pancreatitis was 6.2 (95%CI 3.4-11.3) and only one patient had CBDS at
      the same time. In conclusion, we consider acute pancreatitis and cholangitis both
      as probable long-term complications after ES. 

PMID- 25386096
TI  - Acute diarrhea and metabolic acidosis caused by tuberculous vesico-rectal
      fistula.
AB  - Acquired vesico-rectal fistula is an uncommon complication of pelvic malignant
      tumors, surgical injury, inflammatory disorders such as tuberculosis infection,
      radiotherapy and less commonly diverticulum of the urinary tract. The fistula is
      often identified by urinary tract abnormalities such as dysuria, recurrent
      urinary tract infection, pneumaturia, and fecaluria. Here, we report an unusual
      case of a patient with a vesico-rectal fistula of tuberculous origin, presenting
      with severe acute diarrhea, metabolic acidosis, hyperchloremia and hypokalemia
      while with only mild urinary tract symptoms. The patient was cured by
      tuberculostatic therapy. 

PMID- 25386098
TI  - Overexpressing the NH2-terminal fragment of dentin sialophosphoprotein (DSPP)
      aggravates the periodontal defects in Dspp knockout mice.
AB  - OBJECTIVE: Previous studies have shown that dentin sialophosphoprotein (DSPP) is
      not only essential to the formation and mineralization of dentin but also plays
      an important role in forming and maintaining a healthy periodontium. Under
      physiological conditions, DSPP is proteolytically processed into the NH2-terminal
      and COOH-terminal fragments, and these fragments are believed to perform
      different functions in the mineralized tissues. Previous studies in our group
      have demonstrated that the NH2-terminal fragment of DSPP inhibits the formation
      and mineralization of dentin, while the role of this fragment in periodontium is
      unclear. METHODS: We analyzed the periodontal tissues of the transgenic mice
      overexpressing the NH2-terminal fragment of DSPP in the Dspp knockout background
      (referred to as "Dspp KO/DSP Tg" mice), in comparison with wild type mice and
      Dspp knockout mice. The approaches used in this study included histology, micro
      computed tomography, back scattered scanning electron microscopy and resin-casted
      scanning electron microscopy. RESULTS: Dspp KO/DSP Tg mice exhibited a greater
      reduction of the alveolar bone, more remarkably altered canalicular systems
      around the osteocytes, less cementum, more radical migration of the epithelial
      attachment towards the apical direction, and more severe inflammation in molar
      furcation region, than in the Dspp knockout mice. CONCLUSION: Overexpressing the
      NH2-terminal fragment of DSPP worsened the periodontal defects in Dspp knockout
      mice, indicating that the NH2-terminal fragment of DSPP may exert an inhibitory
      role in the formation and mineralization of hard tissues in the periodontium.

PMID- 25386099
TI  - Synthesis of Pyrrolidines and Pyrroles via Tandem Amination/Cyanation/Alkylation
      and Amination/Oxidation Sequences.
AB  - Starting from a primary amine-tethered alkyne 1, a copper-catalyzed three
      component tandem amination/cyanation/alkylation sequence gives alpha-CN
      pyrrolidine 6 in good yield and regioselectivity. Also, a silver mediated tandem
      amination/oxidation of a secondary amine-tethered alkyne 7 produces
      functionalized pyrrole 8 in good yield. All reactions were conducted in one pot
      without any protection/deprotection steps.

PMID- 25386100
TI  - Near-field surface plasmon effects on Au-double-slit diffraction for
      polychromatic light.
AB  - The surface plasmon effects on near-field diffraction for polychromatic light are
      studied. An Au-double-slit is used as the model and Fresnel integral is employed
      to perform the theoretic analysis. The results are illustrated with numerical
      examples and they show that, compared with the normal double-slit, the plasmon
      effect changes the spectral shift from redshift to blueshift and also enhances
      the intensity peak. This effect can be used in optical data transmission or
      specific spectral selectors. 

PMID- 25386101
TI  - Initial stem cell adhesion on porous silicon surface: molecular architecture of
      actin cytoskeleton and filopodial growth.
AB  - The way cells explore their surrounding extracellular matrix (ECM) during
      development and migration is mediated by lamellipodia at their leading edge,
      acting as an actual motor pulling the cell forward. Lamellipodia are the primary
      area within the cell of actin microfilaments (filopodia) formation. In this work,
      we report on the use of porous silicon (pSi) scaffolds to mimic the ECM of
      mesenchymal stem cells from the dental pulp (DPSC) and breast cancer (MCF-7)
      cells. Our atomic force microscopy (AFM), fluorescence microscopy, and scanning
      electron microscopy (SEM) results show that pSi promoted the appearance of
      lateral filopodia protruding from the DPSC cell body and not only in the
      lamellipodia area. The formation of elongated lateral actin filaments suggests
      that pores provided the necessary anchorage points for protrusion growth.
      Although MCF-7 cells displayed a lower presence of organized actin network on
      both pSi and nonporous silicon, pSi stimulated the formation of extended cell
      protrusions. 

PMID- 25386102
TI  - Cell behaviour on a polyaniline nanoprotrusion structure surface.
AB  - The extracellular matrix provides mechanical support and affects cell behaviour.
      Nanoscale structures have been shown to have functions similar to the
      extracellular matrix. In this study, we fabricated nanoprotrusion structures with
      polyaniline as cell culture plates using a simple method and determined the
      effects of these nanoprotrusion structures on cells. 

PMID- 25386103
TI  - Macropore formation in p-type silicon: toward the modeling of morphology.
AB  - The formation of macropores in silicon during electrochemical etching processes
      has attracted much interest. Experimental evidences indicate that charge
      transport in silicon and in the electrolyte should realistically be taken into
      account in order to be able to describe the macropore morphology. However, up to
      now, none of the existing models has the requested degree of sophistication to
      reach such a goal. Therefore, we have undertaken the development of a
      mathematical model (phase-field model) to describe the motion and shape of the
      silicon/electrolyte interface during anodic dissolution. It is formulated in
      terms of the fundamental expression for the electrochemical potential and
      contains terms which describe the process of silicon dissolution during
      electrochemical attack in a hydrofluoric acid (HF) solution. It should allow us
      to explore the influence of the physical parameters on the etching process and to
      obtain the spatial profiles across the interface of various quantities of
      interest, such as the hole concentration, the current density, or the
      electrostatic potential. As a first step, we find that this model correctly
      describes the space charge region formed at the silicon side of the interface. 

PMID- 25386104
TI  - A promising gene delivery system developed from PEGylated MoS2 nanosheets for
      gene therapy.
AB  - A new class of two-dimensional (2D) nanomaterial, transition metal
      dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic
      physical and chemical properties, has drawn tremendous attention in different
      fields recently. Herein, we for the first time take advantage of the great
      potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers
      for gene delivery and therapy of cancer. In our system, positively charged MoS2
      PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and
      branched polyethylenimine (PEI). The amino end of positively charged
      nanomaterials can bind to the negatively charged small interfering RNA (siRNA).
      After detection of physical and chemical characteristics of the nanomaterial,
      cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was
      investigated as a well-known oncogene, which was a critical regulator of cell
      cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA
      carried by novel nanovector, qPCR and Western blot were used to measure the
      interfering efficiency; apoptosis assay was used to detect the transfection
      effect of PLK1. All results showed that the novel nanocarrier revealed good
      biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability
      without serum interference, thus would have great potential for gene delivery and
      therapy. 

PMID- 25386105
TI  - High performance of carbon nanotubes/silver nanowires-PET hybrid flexible
      transparent conductive films via facile pressing-transfer technique.
AB  - To obtain low sheet resistance, high optical transmittance, small open spaces in
      conductive networks, and enhanced adhesion of flexible transparent conductive
      films, a carbon nanotube (CNT)/silver nanowire (AgNW)-PET hybrid film was
      fabricated by mechanical pressing-transfer process at room temperature. The
      morphology and structure were characterized by scanning electron microscope (SEM)
      and atomic force microscope (AFM), the optical transmittance and sheet resistance
      were tested by ultraviolet-visible spectroscopy (UV-vis) spectrophotometer and
      four-point probe technique, and the adhesion was also measured by 3M sticky tape.
      The results indicate that in this hybrid nanostructure, AgNWs form the main
      conductive networks and CNTs as assistant conductive networks are filled in the
      open spaces of AgNWs networks. The sheet resistance of the hybrid films can reach
      approximately 20.9 to 53.9 Omega/? with the optical transmittance of
      approximately 84% to 91%. The second mechanical pressing step can greatly reduce
      the surface roughness of the hybrid film and enhance the adhesion force between
      CNTs, AgNWs, and PET substrate. This process is hopeful for large-scale
      production of high-end flexible transparent conductive films. 

PMID- 25386106
TI  - Preparation of periodic surface structures on doped poly(methyl metacrylate)
      films by irradiation with KrF excimer laser.
AB  - In this work, we describe laser modification of poly(methyl methacrylate) films
      doped with Fast Red ITR, followed by dopant exclusion from the bulk polymer. By
      this procedure, the polymer can be modified under extremely mild conditions.
      Creation of surface ordered structure was observed already after application of
      15 pulses and 12 mJ cm(-2) fluence. Formation of grating begins in the hottest
      places and tends to form concentric semi-circles around them. The mechanism of
      surface ordered structure formation is attributed to polymer ablation, which is
      more pronounced in the place of higher light intensity. The smoothness of the
      underlying substrate plays a key role in the quality of surface ordered
      structure. Most regular grating structures were obtained on polymer films
      deposited on atomically 'flat' Si substrates. After laser patterning, the dopant
      was removed from the polymer by soaking the film in methanol. 

PMID- 25386107
TI  - Hybrid morphology dependence of CdTe:CdSe bulk-heterojunction solar cells.
AB  - A nanocrystal thin-film solar cell operating on an exciton splitting pattern
      requires a highly efficient separation of electron-hole pairs and transportation
      of separated charges. A hybrid bulk-heterojunction (HBH) nanostructure providing
      a large contact area and interpenetrated charge channels is favorable to an
      inorganic nanocrystal solar cell with high performance. For this freshly appeared
      structure, here in this work, we have firstly explored the influence of hybrid
      morphology on the photovoltaic performance of CdTe:CdSe bulk-heterojunction solar
      cells with variation in CdSe nanoparticle morphology. Quantum dot (QD) or
      nanotetrapod (NT)-shaped CdSe nanocrystals have been employed together with CdTe
      NTs to construct different hybrid structures. The solar cells with the two
      different hybrid active layers show obvious difference in photovoltaic
      performance. The hybrid structure with densely packed and continuously
      interpenetrated two phases generates superior morphological and electrical
      properties for more efficient inorganic bulk-heterojunction solar cells, which
      could be readily realized in the NTs:QDs hybrid. This proved strategy is
      applicable and promising in designing other highly efficient inorganic hybrid
      solar cells. 

PMID- 25386108
TI  - Prognostic Impact of Deficient DNA Mismatch Repair and Mutations in KRAS, and
      BRAFV600E in Patients with Lymph Node-Positive Colon Cancer.
AB  - While tumor stage remains the key determinant of colorectal cancer (CRC)
      prognosis and treatment, there is considerable stage-independent variability in
      clinical outcome. Molecular markers hold promise for explaining variations in
      clinical behavior, and may identify patient subsets with differential efficacy
      and survival after adjuvant chemotherapy which is standard of care for patients
      with lymph node-positive, i.e., stage III, colon cancer. An increased
      understanding of the molecular evolution and progression of CRC has identified
      two major pathways of tumorigenesis that are characterized by chromosomal
      instability or microsatellite instability (MSI). MSI is a consequence of
      deficient DNA mismatch repair (MMR) that is generally due to epigenetic
      inactivation of MLH1 in tumors that often carry mutations in oncogenic BRAFV600E
      . Activating BRAFV600E and KRAS mutations are mutually exclusive and in this
      article, we review the current status of these mutations and MMR status as
      prognostic biomarkers in stage III colon cancers.

PMID- 25386109
TI  - Synthesis and Characterisation of Copper(II) Complexes with Tridentate NNO
      Functionalized Ligand: Density Function Theory Study, DNA Binding Mechanism,
      Optical Properties, and Biological Application.
AB  - The photo physical properties of two mononuclear pentacoordinated copper(II)
      complexes formulated as [Cu(L)(Cl)(H2O)] (1) and [Cu(L)(Br)(H2O)] (2) HL = (1-[(3
      methyl-pyridine-2-ylimino)-methyl]-naphthalen-2-ol) were synthesized and
      characterized by elemental, physicochemical, and spectroscopic methods. The
      density function theory calculations are used to investigate the electronic
      structures and the electronic properties of ligand and complex. The interactions
      of copper(II) complexes towards calf thymus DNA were examined with the help of
      absorption, viscosity, and fluorescence spectroscopic techniques at pH 7.40. All
      spectroscopy's result indicates that complexes show good binding activity to calf
      thymus DNA through groove binding. The optical absorption and fluorescence
      emission properties of microwires were characterized by fluorescence microscope.
      From a spectroscopic viewpoint, all compounds strongly emit green light in the
      solid state. The microscopy investigation suggested that microwires exhibited
      optical waveguide behaviour which are applicable as fluorescent nanomaterials and
      can be used as building blocks for miniaturized photonic devices. Antibacterial
      study reveals that complexes are better antimicrobial agents than free Schiff
      base due to bacterial cell penetration by chelation. Moreover, the antioxidant
      study of the ligand and complexes is evaluated by using 1,1-diphenyl-2
      picrylhydrazyl (DPPH) free-radical assays, which demonstrate that the complexes
      are of higher antioxidant activity than free ligand. 

PMID- 25386110
TI  - Gate-Modulated Graphene Quantum Point Contact Device for DNA Sensing.
AB  - In this paper, we present a computational model to describe the electrical
      response of a constricted graphene nanoribbon (GNR) to biomolecules translocating
      through a nanopore. For this purpose, we use a self-consistent 3D Poisson
      equation solver coupled with an accurate three-orbital tight-binding model to
      assess the ability for a gate electrode to modulate both the carrier
      concentration as well as the conductance in the GNR. We also investigate the role
      of electrolytic screening on the sensitivity of the conductance to external
      charges and find that the gate electrode can either suppress or enhance the
      screening of biomolecular charges in the nanopore depending on the value of its
      potential. Translocating a double-stranded DNA molecule along the pore axis
      imparted a large change in the conductance at particular gate voltages,
      suggesting that such a device can be used to sense translocating biomolecules and
      can be actively tuned to maximize its sensitivity.

PMID- 25386111
TI  - Mentoring Programs to Affect Delinquency and Associated Outcomes of Youth At
      Risk: A Comprehensive Meta-Analytic Review.
AB  - OBJECTIVES: To conduct a meta-analytic review of selective and indicated
      mentoring interventions for effects for youth at risk on delinquency and key
      associated outcomes (aggression, drug use, academic functioning). We also
      undertook the first systematic evaluation of intervention implementation features
      and organization and tested for effects of theorized key processes of mentor
      program effects. METHODS: Campbell Collaboration review inclusion criteria and
      procedures were used to search and evaluate the literature. Criteria included a
      sample defined as at-risk for delinquency due to individual behavior such as
      aggression or conduct problems or environmental characteristics such as residence
      in high-crime community. Studies were required to be random assignment or strong
      quasi-experimental design. Of 163 identified studies published 1970 - 2011, 46
      met criteria for inclusion. RESULTS: Mean effects sizes were significant and
      positive for each outcome category (ranging form d =.11 for Academic Achievement
      to d = .29 for Aggression). Heterogeneity in effect sizes was noted for all four
      outcomes. Stronger effects resulted when mentor motivation was professional
      development but not by other implementation features. Significant improvements in
      effects were found when advocacy and emotional support mentoring processes were
      emphasized. CONCLUSIONS: This popular approach has significant impact on
      delinquency and associated outcomes for youth at-risk for delinquency. While
      evidencing some features may relate to effects, the body of literature is
      remarkably lacking in details about specific program features and procedures.
      This persistent state of limited reporting seriously impedes understanding about
      how mentoring is beneficial and ability to maximize its utility.

PMID- 25386112
TI  - A droplet microfluidic approach to single-stream nucleic acid isolation and
      mutation detection.
AB  - In this work, a droplet microfluidic platform for genetic mutation detection from
      crude biosample is described. Single-stream integration of nucleic acid isolation
      and amplification is realized on a simple fluidic cartridge. Subsequent DNA
      melting curve is employed with signal normalizing algorithm to differentiate
      heterozygous K-ras codon 12 c.25G>A mutant from the wildtype. This technique
      showcases an alternative to modular bench-top approaches for genetic mutation
      screening, which is of interest to decentralized diagnostic platforms.

PMID- 25386113
TI  - Film-based Implants for Supporting Neuron-Electrode Integrated Interfaces for The
      Brain.
AB  - Neural engineering provides promise for cell therapy by integrating the host
      brain with brain-machine-interface technologies in order to externally modulate
      functions. Long-term interfaces with the host brain remain a critical challenge
      due to insufficient graft cell survivability and loss of brain electrode
      sensitivity over time. Here, integrated neuron-electrode interfaces were
      developed on thin flexible and transparent silk films as brain implants.
      Mechanical properties and surface topography of silk films were optimized to
      promote cell survival and alignment of primary rat cortical cells.
      Compartmentalized cultures of living neural circuit and co-patterned electrode
      arrays were incorporated on the silk films with built-in wire connections.
      Electrical stimulation via electrodes embedded in the films activated surrounding
      neurons evoked calcium responses. In mice brains the silk film implants showed
      conformal contact capable of modulating host brain cells with minimal
      inflammatory response and stable indwelling for weeks. The approach of combining
      cell therapy and brain electrodes could provide sustained functional brain
      machine interfaces with ex vivo control of neuron-electrode interface with
      spatial and temporal precision.

PMID- 25386114
TI  - Detection of residual cognitive function through non-spontaneous eye movement in
      a patient with advanced frontotemporal dementia.
AB  - As dementia progresses, cognitive functions decline in patients, and caregivers
      and other support staff gradually lose the means to communicate with them.
      However, some caregivers believe that patients can still recognize their
      surroundings even when they show akinesis with mutism. In this study, we observed
      eye movements (preferential-looking paradigm) to detect the presence of residual
      cognitive functions in a patient with severe frontotemporal dementia (FTD). The
      subject was a 76-year-old female. At the time of observation, she had lost all
      spontaneous activities. Magnetic resonance imaging (MRI) imaging showed dense
      atrophy of the bilateral frontotemporal lobe, but the parieto-occipital lobe was
      preserved. A preferential-looking paradigm was used in the experiment, whereby
      two different faces (learned and non-learned) were simultaneously presented to
      the patient on a TV monitor. As a result, we found no significant differences in
      looking time between the two faces. However, when the saccade timing to the
      presented faces was examined, a much longer latency was observed for the right
      than the left side of the target faces. Even though the patient had lost capacity
      for spontaneous activity due to severe FTD, we were able to observe partial
      residual cognitive ability using the eye-movement paradigm. 

PMID- 25386115
TI  - Unexpected multiplicity of QRFP receptors in early vertebrate evolution.
AB  - The neuropeptide QRFP, also called 26RFa, and its G protein-coupled receptor
      GPR103 have been identified in all vertebrates investigated. In mammals, this
      peptide-receptor pair has been found to have several effects including
      stimulation of appetite. Recently, we reported that a QRFP peptide is present in
      amphioxus, Branchiostoma floridae, and we also identified a QRFP receptor (QRFPR)
      that mediates a functional response to sub-nanomolar concentrations of the
      amphioxus peptide as well as short and long human QRFP (Xu et al., submitted).
      Because the ancestral vertebrate underwent two tetraploidizations, it might be
      expected that duplicates of the QRFP gene and its receptor gene may exist.
      Indeed, we report here the identification of multiple vertebrate QRFPR genes.
      Three QRFPR genes are present in the coelacanth Latimeria chalumnae, representing
      an early diverging sarcopterygian lineage. Three QRFPR genes are present in the
      basal actinopterygian fish, the spotted gar. Phylogenetic and chromosomal
      analyses show that only two of these receptor genes are orthologous between the
      two species, thus demonstrating a total of four distinct vertebrate genes. Three
      of the QRFPR genes resulted from the early vertebrate tetraploidizations and were
      copied along with syntenic neuropeptide Y receptor genes. The fourth QRFPR gene
      may be an even older and distinct lineage. Because mammals and birds have only a
      single QRFPR gene, this means that three genes have been lost in these lineages,
      and at least one of these was lost independently in mammals and birds because it
      is still present in a turtle. In conclusion, these results show that the QRFP
      system gained considerable complexity in the early stages of vertebrate evolution
      and still maintains much of this in some lineages, and that it has been
      secondarily reduced in mammals. 

PMID- 25386116
TI  - The choroid plexuses and their impact on developmental neurogenesis.
AB  - During brain development the neural stem cells are regulated by both intrinsic
      and extrinsic sources. One site of origin of extrinsic regulation is the
      developing choroid plexuses, primely situated inside the cerebral ventricles. The
      choroid plexuses are very active in terms of both secretion and barrier function
      as soon as they appear during development and control the production and contents
      of cerebrospinal fluid (CSF). This suggests that regulated secretion of signaling
      molecules from the choroid plexuses into CSF can regulate neural stem cell
      behavior (as they are in direct contact with CSF) and thereby neurogenesis and
      brain development. Here, choroid plexus development, particularly with regards to
      molecular regulation and specification, is reviewed. This is followed by a review
      and discussion of the role of the developing choroid plexuses in brain
      development. In particular, recent evidence suggests a region-specific reciprocal
      regulation between choroid plexuses and the neural stem cells. This is
      accomplished by site-specific secretion of signaling molecules from the different
      choroid plexuses into CSF, as well as brain region specific competence of the
      neural stem cells to respond to the signaling molecules present in CSF. In
      conclusion, although in its infancy, the field of choroid plexus regulation of
      neurogenesis has already and will likely continue to shed new light on our
      understanding of the control and fine-tuning of overall brain development. 

PMID- 25386117
TI  - Shaping inhibition: activity dependent structural plasticity of GABAergic
      synapses.
AB  - Inhibitory transmission through the neurotransmitter gamma-aminobutyric acid
      (GABA) shapes network activity in the mammalian cerebral cortex by filtering
      synaptic incoming information and dictating the activity of principal cells. The
      incredibly diverse population of cortical neurons that use GABA as
      neurotransmitter shows an equally diverse range of mechanisms that regulate
      changes in the strength of GABAergic synaptic transmission and allow them to
      dynamically follow and command the activity of neuronal ensembles. Similarly to
      glutamatergic synaptic transmission, activity-dependent functional changes in
      inhibitory neurotransmission are accompanied by alterations in GABAergic synapse
      structure that range from morphological reorganization of postsynaptic density to
      de novo formation and elimination of inhibitory contacts. Here we review several
      aspects of structural plasticity of inhibitory synapses, including its induction
      by different forms of neuronal activity, behavioral and sensory experience and
      the molecular mechanisms and signaling pathways involved. We discuss the
      functional consequences of GABAergic synapse structural plasticity for
      information processing and memory formation in view of the heterogenous nature of
      the structural plasticity phenomena affecting inhibitory synapses impinging on
      somatic and dendritic compartments of cortical and hippocampal neurons. 

PMID- 25386119
TI  - Role of IFN-gamma and LPS on neuron/glial co-cultures infected by Neospora
      caninum.
AB  - Neospora caninum causes cattle abortion and neurological symptoms in dogs.
      Although infection is usually asymptomatic, classical neurological symptoms of
      neosporosis may be associated with encephalitis. This parasite can grow in brain
      endothelial cells without markedly damages, but it can modulate the cellular
      environment to promote its survival in the brain. In previous studies, we
      described that IFN-gamma decreased the parasite proliferation and down regulated
      nitric oxide (NO) production in astrocyte/microglia cultures. However, it remains
      unclear how glial cells respond to N. caninum in the presence of neurons.
      Therefore, we evaluated the effect of 300 IU/mL IFN-gamma or 1.0 mg/mL of LPS on
      infected rat neuron/glial co-cultures. After 72 h of infection, LPS did not
      affect the mitochondrial dehydrogenase activity. However, IFN-gamma decreased
      this parameter by 15.5 and 12.0% in uninfected and infected cells, respectively.
      The number of tachyzoites decreased 54.1 and 44.3% in cells stimulated with IFN
      gamma and LPS, respectively. Infection or LPS treatment did not change NO
      production. On the other hand, IFN-gamma induced increased nitrite release in
      55.7%, but the infection reverted this induction. IL-10 levels increased only in
      infected cultures (treated or not), meanwhile PGE2 release was improved in IFN
      gamma/infected or LPS/infected cells. Although IFN-gamma significantly reduced
      the neurite length in uninfected cultures (42.64%; p < 0.001), this inflammatory
      cytokine reverted the impairment of neurite outgrowth induced by the infection
      (81.39%). The results suggest a neuroprotective potential response of glia to N.
      caninum infection under IFN-gamma stimulus. This observation contributes to
      understand the immune mediated mechanisms of neosporosis in central nervous
      system (CNS). 

PMID- 25386118
TI  - A perspective on the role of class III semaphorin signaling in central nervous
      system trauma.
AB  - Traumatic injury of the central nervous system (CNS) has severe impact on the
      patients' quality of life and initiates many molecular and cellular changes at
      the site of insult. Traumatic CNS injury results in direct damage of the axons of
      CNS neurons, loss of myelin sheaths, destruction of the surrounding vascular
      architecture and initiation of an immune response. Class III semaphorins (SEMA3s)
      are present in the neural scar and influence a wide range of molecules and cell
      types in and surrounding the injured tissue. SEMA3s and their receptors,
      neuropilins (NRPs) and plexins (PLXNs) were initially studied because of their
      involvement in repulsive axon guidance. To date, SEMA3 signaling is recognized to
      be of crucial importance for re-vascularization, the immune response and
      remyelination. The purpose of this review is to summarize and discuss how SEMA3s
      modulate these processes that are all crucial components of the tissue response
      to injury. Most of the functions for SEMA3s are achieved through their binding
      partners NRPs, which are also co-receptors for a variety of other molecules
      implicated in the above processes. The most notable ligands are members of the
      vascular endothelial growth factor (VEGF) family and the transforming growth
      factor family. Therefore, a second aim is to highlight the overlapping or
      competing signaling pathways that are mediated through NRPs in the same
      processes. In conclusion, we show that the role of SEMA3s goes beyond inhibiting
      axonal regeneration, since they are also critical modulators of re
      vascularization, the immune response and re-myelination. 

PMID- 25386120
TI  - Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome: insights
      into syndromic hearing loss.
AB  - Mutation of the GJB2 gene, which encodes the connexin 26 (Cx26) gap junction (GJ)
      protein, is the most common cause of hereditary, sensorineural hearing loss. Cx26
      is not expressed in hair cells, but is widely expressed throughout the non
      sensory epithelial cells of the cochlea. Most GJB2 mutations produce non
      syndromic deafness, but a subset produces syndromic deafness in which profound
      hearing loss is accompanied by a diverse array of infectious and neoplastic
      cutaneous disorders that can be fatal. Although GJ channels, which are assembled
      by the docking of two, so-called hemichannels (HCs), have been the main focus of
      deafness-associated disease models, it is now evident that the HCs themselves can
      function in the absence of docking and contribute to signaling across the cell
      membrane as a novel class of ion channel. A notable feature of syndromic deafness
      mutants is that the HCs exhibit aberrant behaviors providing a plausible basis
      for disease that is associated with excessive or altered contributions of Cx26
      HCs that, in turn, lead to compromised cell integrity. Here we discuss some of
      the aberrant Cx26 HC properties that have been described for mutants associated
      with keratitis-ichthyosis-deafness (KID) syndrome, a particularly severe Cx26
      associated syndrome, which shed light on genotype-phenotype relationships and
      causes underlying cochlear dysfunction. 

PMID- 25386121
TI  - Connections between EM2-containing terminals and GABA/MU-opioid receptor co
      expressing neurons in the rat spinal trigeminal caudal nucleus.
AB  - Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect via the MU
      opioid receptor (MOR). To provide morphological evidence for the pain control
      effect of EM2, the synaptic connections between EM2-immunoreactive (IR) axonal
      terminals and gamma-amino butyric acid (GABA)/MOR co-expressing neurons in lamina
      II of the spinal trigeminal caudal nucleus (Vc) were investigated in the rat.
      Dense EM2-, MOR- and GABA-IR fibers and terminals were mainly observed in lamina
      II of the Vc. Within lamina II, GABA- and MOR-neuronal cell bodies were also
      encountered. The results of immunofluorescent histochemical triple-staining
      showed that approximately 14.2 or 18.9% of GABA-IR or MOR-IR neurons also showed
      MOR- or GABA-immunopositive staining in lamina II; approximately 45.2 and 36.1%
      of the GABA-IR and MOR-IR neurons, respectively, expressed FOS protein in their
      nuclei induced by injecting formalin into the left lower lip of the mouth. Most
      of the GABA/MOR, GABA/FOS, and MOR/FOS double-labeled neurons made close contacts
      with EM2-IR fibers and terminals. Immuno-electron microscopy confirmed that the
      EM2-IR terminals formed synapses with GABA-IR or MOR-IR dendritic processes and
      neuronal cell bodies in lamina II of the Vc. These results suggest that EM2 might
      participate in pain transmission and modulation by binding to MOR-IR and
      GABAergic inhibitory interneuron in lamina II of the Vc to exert inhibitory
      effect on the excitatory interneuron in lamina II and projection neurons in
      laminae I and III.

PMID- 25386122
TI  - Properties of bilateral spinocerebellar activation of cerebellar cortical
      neurons.
AB  - We aimed to explore the cerebellar cortical inputs from two spinocerebellar
      pathways, the spinal border cell-component of the ventral spinocerebellar tract
      (SBC-VSCT) and the dorsal spinocerebellar tract (DSCT), respectively, in the
      sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by
      electrical stimulation of the contralateral lateral funiculus (coLF) and the
      ipsilateral LF (iLF) at lower thoracic levels. Most granule cells in sublobule C1
      did not respond at all but part of the granule cell population displayed high
      intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and
      Purkinje cell simple spikes responded to input from both LFs, although Golgi
      cells could be more selective. In addition, a small population of granule cells
      responded to input from both the coLF and the iLF. However, in these cases,
      similarities in the temporal topography and magnitude of the responses suggested
      that the same axons were stimulated from the two LFs, i.e., that the axons of
      individual spinocerebellar neurons could be present in both funiculi. This was
      also confirmed for a population of spinal neurons located within known locations
      of SBC-VSCT neurons and dorsal horn (dh) DSCT neurons. We conclude that bilateral
      spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and
      DSCT systems that provide the input can also be organized bilaterally. The
      implications for the traditional functional separation of VSCT and DSCT systems
      and the issue whether granule cells primarily integrate functionally similar
      information or not are discussed.

PMID- 25386123
TI  - Retronasal odor concentration coding in glomeruli of the rat olfactory bulb.
AB  - The mammalian olfactory system processes odorants presented orthonasally
      (inhalation through the nose) and also retronasally (exhalation), enabling
      identification of both external as well as internal objects during food
      consumption. There are distinct differences between ortho- and retronasal air
      flow patterns, psychophysics, multimodal integration, and glomerular responses.
      Recent work indicates that rats can also detect odors retronasally, that rats can
      associate retronasal odors with tastes, and that their olfactory bulbs (OBs) can
      respond to retronasal odorants but differently than to orthonasal odors. To
      further characterize retronasal OB input activity patterns, experiments here
      focus on determining the effects of odor concentration on glomerular activity by
      monitoring calcium activity in the dorsal OB of rats using a dextran-conjugated
      calcium-sensitive dye in vivo. Results showed reliable concentration-response
      curves that differed between odorants, and recruitment of additional glomeruli,
      as odor concentration increased. We found evidence of different concentration
      response functions between glomeruli, that in turn depended on odor. Further, the
      relation between dynamics and concentration differed remarkably among retronasal
      odorants. These dynamics are suggested to reduce the odor map ambiguity based on
      response amplitude. Elucidating the coding of retronasal odor intensity is
      fundamental to the understanding of feeding behavior and the neural basis of
      flavor. These data further establish and refine the rodent model of flavor
      neuroscience. 

PMID- 25386124
TI  - Saccadic body turns in walking Drosophila.
AB  - Drosophila melanogaster structures its optic flow during flight by interspersing
      translational movements with abrupt body rotations. Whether these "body saccades"
      are accompanied by steering movements of the head is a matter of debate. By
      tracking single flies moving freely in an arena, we now discovered that walking
      Drosophila also perform saccades. Movement analysis revealed that the flies
      separate rotational from translational movements by quickly turning their bodies
      by 15 degrees within a tenth of a second. Although walking flies moved their
      heads by up to 20 degrees about their bodies, their heads moved with the bodies
      during saccadic turns. This saccadic strategy contrasts with the head saccades
      reported for e.g., blowflies and honeybees, presumably reflecting optical
      constraints: modeling revealed that head saccades as described for these latter
      insects would hardly affect the retinal input in Drosophila because of the lower
      acuity of its compound eye. The absence of head saccades in Drosophila was
      associated with the absence of haltere oscillations, which seem to guide head
      movements in other flies. In addition to adding new twists to Drosophila walking
      behavior, our analysis shows that Drosophila does not turn its head relative to
      its body when turning during walking. 

PMID- 25386125
TI  - "Executive functions" cannot be distinguished from general intelligence: two
      variations on a single theme within a symphony of latent variance.
AB  - The empirical foundation of executive control function (ECF) remains
      controversial. We have employed structural equation models (SEM) to explicitly
      distinguish domain-specific variance in executive function (EF) performance from
      memory (MEM) and shared cognitive performance variance, i.e., Spearman's "g." EF
      does not survive adjustment for both MEM and g in a well fitting model of data
      obtained from non-demented older persons (N = 193). Instead, the variance in
      putative EF measures is attributable only to g, and related to functional status
      only through a fraction of that construct (i.e., "d"). d is a homolog of the
      latent variable delta, which we have previously associated specifically with the
      Default Mode Network (DMN). These findings undermine the validity of EF and its
      putative association with the frontal lobe. ECF may have no existence independent
      of general intelligence, and no functionally salient association with the frontal
      lobe outside of that structure's contribution to the DMN. 

PMID- 25386126
TI  - Winning the game: brain processes in expert, young elite and amateur table tennis
      players.
AB  - THIS STUDY TESTED TWO HYPOTHESES: (1) compared with amateurs and young elite,
      expert table tennis players are characterized by enhanced cortical activation in
      the motor and fronto-parietal cortex during motor imagery in response to table
      tennis videos; (2) in elite athletes, world rank points are associated with
      stronger cortical activation. To this aim, electroencephalographic data were
      recorded in 14 expert, 15 amateur and 15 young elite right-handed table tennis
      players. All subjects watched videos of a serve and imagined themselves
      responding with a specific table tennis stroke. With reference to a baseline
      period, power decrease/increase of the sensorimotor rhythm (SMR) during the
      pretask- and task period indexed the cortical activation/deactivation (event
      related desynchronization/synchronization, ERD/ERS). Regarding hypothesis (1), 8
      10 Hz SMR ERD was stronger in elite athletes than in amateurs with an
      intermediate ERD in young elite athletes in the motor cortex. Regarding
      hypothesis (2), there was no correlation between ERD/ERS in the motor cortex and
      world rank points in elite experts, but a weaker ERD in the fronto-parietal
      cortex was associated with higher world rank points. These results suggest that
      motor skill in table tennis is associated with focused excitability of the motor
      cortex during reaction, movement planning and execution with high attentional
      demands. Among elite experts, less activation of the fronto-parietal attention
      network may be necessary to become a world champion.

PMID- 25386127
TI  - Contribution of emotional and motivational neurocircuitry to cue-signaled active
      avoidance learning.

PMID- 25386128
TI  - Affective and cognitive prefrontal cortex projections to the lateral habenula in
      humans.
AB  - Anterior insula (AI) and dorsal ACC (dACC) are known to process information about
      pain, loss, adversities, bad, harmful or suboptimal choices and consequences that
      threaten survival or well-being. Also pregenual ACC (pgACC) is linked to loss and
      pain, being activated by sad thoughts and regrets. Lateral habenula (LHb) is
      stimulated by predicted and received pain, discomfort, aversive outcome, loss.
      Its chronic stimulation makes us feel worse/low and gradually stops us choosing
      and moving for the suboptimal or punished choices, by direct and indirect (via
      rostromedial tegmental nucleus, RMTg) inhibition of dorsal raphe nucleus (DRN)
      and VTA/SNc. The response selectivity of LHb neurons suggests their cortical
      input from affective and cognitive evaluative regions that make expectations
      about bad, unpleasant or suboptimal outcomes. Based on these facts I predicted
      direct dACC, pgACC and AI projections to LHb, which form part of an adversity
      processing circuit that learns to avoid bad outcomes by suppressing dopamine and
      serotonin signal. To test this connectivity I used Diffusion Tensor Imaging
      (DTI). I found dACC, pgACC, AI and caudolateral OFC (clOFC) projections to LHb. I
      predicted no corticohabenular projections from the reward processing regions:
      medial OFC (mOFC) and ventral ACC (vACC) because both respond most strongly to
      good, high valued stimuli and outcomes, inducing dopamine and serotonin release.
      This lack of LHb projections was confirmed for vACC and likely for mOFC. The
      surprising findings were the corticohabenular projections from the cognitive
      prefrontal cortex regions, known for flexible reasoning, planning and combining
      whatever information are relevant for reaching current goals. I propose that the
      prefrontohabenular projections provide a teaching signal for value-based choice
      behavior, to learn to deselect, avoid or inhibit the potentially harmful, low
      valued or wrong choices, goals, strategies, predictions and ways of doing things,
      to prevent bad or suboptimal consequences. 

PMID- 25386129
TI  - Emotion regulation strategies can predict task-switching abilities in euthymic
      bipolar patients.
AB  - This study examined task-switching abilities and emotion regulation strategies in
      euthymic bipolar patients (EBP). Forty EBP and 40 healthy individuals performed
      face categorization tasks where they switched between emotion and non-emotion
      (i.e., gender) features among faces and completed emotion regulation
      questionnaire (Gross and John, 2003). Subject groups showed substantial
      differences in task-switching abilities and emotion regulation strategies: (1)
      there was a dissociation between emotion and gender classification in EBP. The
      switch cost was larger [i.e., higher reaction times (RTs) on switch as compared
      to no-switch trials] for gender categorization as compared to the emotion
      categorization task. In contrast, such asymmetries were absent among healthy
      participants. The differential pattern of task switching reflected functional
      disturbances in frontotemporal neural system and an attentional bias to emotion
      features of the faces in EBP. This suggests that when a euthymic bipolar patient
      is preoccupied with emotion recognition, an instruction to perform gender
      categorization results in greater cost on RTs. (2) In contrast to healthy
      individuals, EBP reported more frequent use of emotion suppression and lesser use
      of cognitive reappraisal as emotion regulation strategy. (3) Emotion regulation
      was found to be a significant predictor of task-switching abilities. It is argued
      that task switching deficits rely on maladaptive emotion regulation strategies in
      EBP specifically when tasks of emotional significance are involved. 

PMID- 25386130
TI  - Is the brain a resource-cheapskate?

PMID- 25386131
TI  - The brain's sense of walking: a study on the intertwine between locomotor imagery
      and internal locomotor models in healthy adults, typically developing children
      and children with cerebral palsy.
AB  - Motor imagery and internal motor models have been deeply investigated in
      literature. It is well known that the development of motor imagery occurs during
      adolescence and it is limited in people affected by cerebral palsy. However, the
      roles of motor imagery and internal models in locomotion as well as their
      intertwine received poor attention. In this study we compared the performances of
      healthy adults (n = 8, 28.1 +/- 5.1 years old), children with typical development
      (n = 8, 8.1 +/- 3.8 years old) and children with cerebral palsy (CCP) (n = 12,
      7.5 +/- 2.9 years old), measured by an optoelectronic system and a trunk-mounted
      wireless inertial magnetic unit, during three different tasks. Subjects were
      asked to achieve a target located at 2 or 3 m in front of them simulating their
      walking by stepping in place, or actually walking blindfolded or normally walking
      with open eyes. Adults performed a not significantly different number of steps (p
      = 0.761) spending not significantly different time between tasks (p = 0.156).
      Children with typical development showed task-dependent differences both in terms
      of number of steps (p = 0.046) and movement time (p = 0.002). However, their
      performance in simulated and blindfolded walking (BW) were strictly correlated (R
      = 0.871 for steps, R = 0.673 for time). Further, their error in BW was in mean
      only of -2.2% of distance. Also CCP showed significant differences in number of
      steps (p = 0.022) and time (p < 0.001), but neither their number of steps nor
      their movement time recorded during simulated walking (SW) were found correlated
      with those of blindfolded and normal walking (NW). Adults used a unique strategy
      among different tasks. Children with typical development seemed to be less
      reliable on their motor predictions, using a task-dependent strategy probably
      more reliable on sensorial feedback. CCP showed less efficient performances,
      especially in SW, suggesting an altered locomotor imagery. 

PMID- 25386132
TI  - Medial efferent mechanisms in children with auditory processing disorders.
AB  - Auditory processing disorder (APD) affects about 2-5% of children. However, the
      nature of this disorder is poorly understood. Children with APD typically have
      difficulties in complex listening situations. One mechanism thought to aid in
      listening-in-noise is the medial olivocochlear (MOC) inhibition. The purpose of
      this review was to critically analyze the published data on MOC inhibition in
      children with APD to determine whether the MOC efferents are involved in these
      individuals. The otoacoustic emission (OAE) methods used to assay MOC reflex were
      examined in the context of the current understanding of OAE generation
      mechanisms. Relevant literature suggests critical differences in the study
      population and OAE methods. Variables currently known to influence MOC reflex
      measurements, for example, middle-ear muscle reflexes or OAE signal-to-noise
      ratio, were not controlled in most studies. The use of potentially weaker OAE
      methods and the remarkable heterogeneity across studies does not allow for a
      definite conclusion whether or not the MOC reflex is altered in children with
      APD. Further carefully designed studies are needed to confirm the involvement of
      MOC efferents in APD. Knowledge of efferent functioning in children with APD
      would be mechanistically and clinically beneficial. 

PMID- 25386133
TI  - On the connection between level of education and the neural circuitry of emotion
      perception.
AB  - Through education, a social group transmits accumulated knowledge, skills,
      customs, and values to its members. So far, to the best of our knowledge, the
      association between educational attainment and neural correlates of emotion
      processing has been left unexplored. In a retrospective analysis of The
      Netherlands Study of Depression and Anxiety (NESDA) functional magnetic resonance
      imaging (fMRI) study, we compared two groups of fourteen healthy volunteers with
      intermediate and high educational attainment, matched for age and gender. The
      data concerned event-related fMRI of brain activation during perception of facial
      emotional expressions. The region of interest (ROI) analysis showed stronger
      right amygdala activation to facial expressions in participants with lower
      relative to higher educational attainment (HE). The psychophysiological
      interaction analysis revealed that participants with HE exhibited stronger right
      amygdala-right insula connectivity during perception of emotional and neutral
      facial expressions. This exploratory study suggests the relevance of educational
      attainment on the neural mechanism of facial expressions processing. 

PMID- 25386134
TI  - Modeling the shape hierarchy for visually guided grasping.
AB  - The monkey anterior intraparietal area (AIP) encodes visual information about
      three-dimensional object shape that is used to shape the hand for grasping. We
      modeled shape tuning in visual AIP neurons and its relationship with curvature
      and gradient information from the caudal intraparietal area (CIP). The main goal
      was to gain insight into the kinds of shape parameterizations that can account
      for AIP tuning and that are consistent with both the inputs to AIP and the role
      of AIP in grasping. We first experimented with superquadric shape parameters. We
      considered superquadrics because they occupy a role in robotics that is similar
      to AIP, in that superquadric fits are derived from visual input and used for
      grasp planning. We also experimented with an alternative shape parameterization
      that was based on an Isomap dimension reduction of spatial derivatives of depth
      (i.e., distance from the observer to the object surface). We considered an Isomap
      based model because its parameters lacked discontinuities between similar shapes.
      When we matched the dimension of the Isomap to the number of superquadric
      parameters, the superquadric model fit the AIP data somewhat more closely.
      However, higher-dimensional Isomaps provided excellent fits. Also, we found that
      the Isomap parameters could be approximated much more accurately than
      superquadric parameters by feedforward neural networks with CIP-like inputs. We
      conclude that Isomaps, or perhaps alternative dimension reductions of visual
      inputs to AIP, provide a promising model of AIP electrophysiology data. Further
      work is needed to test whether such shape parameterizations actually provide an
      effective basis for grasp control. 

PMID- 25386135
TI  - A comparative analysis of three non-invasive human-machine interfaces for the
      disabled.
AB  - In the framework of rehabilitation robotics, a major role is played by the human
      machine interface (HMI) used to gather the patient's intent from biological
      signals, and convert them into control signals for the robotic artifact.
      Surprisingly, decades of research have not yet declared what the optimal HMI is
      in this context; in particular, the traditional approach based upon surface
      electromyography (sEMG) still yields unreliable results due to the inherent
      variability of the signal. To overcome this problem, the scientific community has
      recently been advocating the discovery, analysis, and usage of novel HMIs to
      supersede or augment sEMG; a comparative analysis of such HMIs is therefore a
      very desirable investigation. In this paper, we compare three such HMIs employed
      in the detection of finger forces, namely sEMG, ultrasound imaging, and pressure
      sensing. The comparison is performed along four main lines: the accuracy in the
      prediction, the stability over time, the wearability, and the cost. A
      psychophysical experiment involving ten intact subjects engaged in a simple
      finger-flexion task was set up. Our results show that, at least in this
      experiment, pressure sensing and sEMG yield comparably good prediction accuracies
      as opposed to ultrasound imaging; and that pressure sensing enjoys a much better
      stability than sEMG. Given that pressure sensors are as wearable as sEMG
      electrodes but way cheaper, we claim that this HMI could represent a valid
      alternative/augmentation to sEMG to control a multi-fingered hand prosthesis. 

PMID- 25386136
TI  - Illuminating the role of cholinergic signaling in circuits of attention and
      emotionally salient behaviors.
AB  - Acetylcholine (ACh) signaling underlies specific aspects of cognitive functions
      and behaviors, including attention, learning, memory and motivation. Alterations
      in ACh signaling are involved in the pathophysiology of multiple neuropsychiatric
      disorders. In the central nervous system, ACh transmission is mainly guaranteed
      by dense innervation of select cortical and subcortical regions from disperse
      groups of cholinergic neurons within the basal forebrain (BF; e.g., diagonal
      band, medial septal, nucleus basalis) and the pontine-mesencephalic nuclei,
      respectively. Despite the fundamental role of cholinergic signaling in the CNS
      and the long standing knowledge of the organization of cholinergic circuitry,
      remarkably little is known about precisely how ACh release modulates cortical and
      subcortical neural activity and the behaviors these circuits subserve. Growing
      interest in cholinergic signaling in the CNS focuses on the mechanism(s) of
      action by which endogenously released ACh regulates cognitive functions, acting
      as a neuromodulator and/or as a direct transmitter via nicotinic and muscarinic
      receptors. The development of optogenetic techniques has provided a valuable
      toolbox with which we can address these questions, as it allows the selective
      manipulation of the excitability of cholinergic inputs to the diverse array of
      cholinergic target fields within cortical and subcortical domains. Here, we
      review recent papers that use the light-sensitive opsins in the cholinergic
      system to elucidate the role of ACh in circuits related to attention and
      emotionally salient behaviors. In particular, we highlight recent optogenetic
      studies which have tried to disentangle the precise role of ACh in the modulation
      of cortical-, hippocampal- and striatal-dependent functions. 

PMID- 25386137
TI  - Instrumented functional reach test differentiates individuals at high risk for
      Parkinson's disease from controls.
AB  - The functional reach (FR) test as a complex measure of balance including limits
      of stability has been proven to differentiate between patients with Parkinson's
      disease (PD) and controls (CO). Recently, it has been shown that the
      instrumentation of the FR (iFR) with a wearable sensor may increase this
      diagnostic accuracy. This cross-sectional study aimed at investigating whether
      the iFR has the potential to differentiate individuals with high risk for PD
      (HRPD) from CO, as the delineation of such individuals would allow for, e.g.,
      early neuromodulation. Thirteen PD patients, 13 CO, and 31 HRPD were
      investigated. HRPD was defined by presence of an enlarged area of
      hyperechogenicity in the mesencephalon on transcranial sonography and either one
      motor sign or two risk and prodromal markers of PD. All participants were asked
      to reach with their right arm forward as far as possible and hold this position
      for 10 s. During this period, sway parameters were assessed with an accelerometer
      (Dynaport, McRoberts) worn at the lower back. Extracted parameters that differed
      significantly between PD patients and CO in our cohort [FR distance (shorter in
      PD), anterior-posterior and mediolateral acceleration (both lower in PD)] as well
      as JERK, which has been shown to differentiate HRPD from CO and PD in a previous
      study, were included in a model, which was then used to differentiate HRPD from
      CO. The model yielded an area under the curve of 0.77, with a specificity of 85%,
      and a sensitivity of 74%. These results suggest that the iFR can contribute to an
      assessment panel focusing on the definition of HRPD individuals. 

PMID- 25386138
TI  - Holistic face perception in young and older adults: effects of feedback and
      attentional demand.
AB  - Evidence exists for age-related decline in face cognition ability. However, the
      extents to which attentional demand and flexibility to adapt viewing strategies
      contribute to age-related decline in face cognition tests is poorly understood.
      Here, we studied holistic face perception in older (age range 65-78 years, mean
      age 69.9) and young adults (age range 20-32 years, mean age 23.1) using the
      complete design for a sequential study-test composite face task (Richler et al.,
      2008b). Attentional demand was varied using trials that required participants to
      attend to both face halves and to redirect attention to one face half during the
      test (high attentional demand), and trials that allowed participants to keep a
      pre-adjusted focus (low attentional demand). We also varied viewing time and
      provided trial-by-trial feedback or no feedback. We observed strong composite
      effects, which were larger for the elderly in all conditions, independent of
      viewing time. Composite effects were smaller for low attentional demand, and
      larger for high attentional demand. No age-related differences were found in this
      respect. Feedback also reduced the composite effects in both age groups. Young
      adults could benefit from feedback in conditions with low and high attentional
      demands. Older adults performed better with feedback only in trials with low
      attentional demand. When attentional demand was high, older adults could no
      longer use the feedback signal, and performed worse with feedback than without.
      These findings suggest that older adults tend to use a global focus for faces,
      albeit piecemeal analysis is required for the task, and have difficulties
      adapting their viewing strategies when task demands are high. These results are
      consistent with the idea that elderly rely more on holistic strategies as a means
      to reduce perceptual and cognitive load when processing resources are limited
      (Konar et al., 2013). 

PMID- 25386139
TI  - Accelerating neuronal aging in in vitro model brain disorders: a focus on
      reactive oxygen species.
AB  - In this review, we discuss insights gained through the use of stem cell
      preparations regarding the modeling of neurological diseases, the need for aging
      neurons derived from pluripotent stem cells to further advance the study of late
      onset adult neurological diseases, and the extent to which mechanisms linked to
      the mismanagement of reactive oxygen species (ROS). The context of these issues
      can be revealed using the three disease states of Parkinson's (PD), Alzheimer's
      (AD), and schizophrenia, as considerable insights have been gained into these
      conditions through the use of stem cells in terms of disease etiologies and the
      role of oxidative stress. The latter subject is a primary area of interest of our
      group. After discussing the molecular models of accelerated aging, we highlight
      the role of ROS for the three diseases explored here. Importantly, we do not seek
      to provide an extensive account of all genetic mutations for each of the three
      disorders discussed in this review, but we aim instead to provide a conceptual
      framework that could maximize the gains from merging the approaches of stem cell
      microsystems and the study of oxidative stress in disease in order to optimize
      therapeutics and determine new molecular targets against oxidative stress that
      spare stem cell proliferation and development. 

PMID- 25386140
TI  - Somatosensory mismatch response in young and elderly adults.
AB  - Aging is associated with cognitive decline and alterations in early perceptual
      processes. Studies in the auditory and visual sensory modalities have shown that
      the mismatch negativity [or the mismatch response (MMR)], an event-related
      potential (ERP) elicited by a deviant stimulus in a background of homogenous
      events, diminishes with aging and cognitive decline. However, the effects of
      aging on the somatosensory MMR (sMMR) are not known. In the current study, we
      recorded ERPs to electrical pulses to different fingers of the left hand in a
      passive oddball experiment in young (22-36 years) and elderly (66-95 years)
      adults engaged in a visual task. The MMR was found to deviants as compared to
      standards at two latency ranges: 180-220 ms and 250-290 ms post-stimulus onset.
      At 180-220 ms, within the young, the MMR was found at medial electrode sites,
      whereas aged did not show any amplitude difference between the stimulus types at
      the same latency range. At 250-290 ms, the MMR was evident with attenuated
      amplitude and narrowed scalp distribution among aged (Fz) compared to young
      (fronto-centrally and lateral parietal sites). Hence, the results reveal that the
      somatosensory change detection mechanism is altered in aging. The sMMR can be
      used as a reliable measure of age-related changes in sensory-cognitive functions.

PMID- 25386141
TI  - Combined frontal and parietal P300 amplitudes indicate compensated cognitive
      processing across the lifespan.
AB  - In the present study the frontal and parietal P300, elicited in an auditory
      oddball paradigm were investigated in a large sample of healthy participants (N =
      1572), aged 6-87. According to the concepts of the compensation-related
      utilization of neural circuits hypothesis (CRUNCH) it was hypothesized that the
      developmental trajectories of the frontal P300 would reach a maximum in amplitude
      at an older age than the amplitude of the parietal P300 amplitude. In addition,
      the amplitude of the frontal P300 was expected to increase with aging in
      adulthood in contrast to a decline in amplitude of the parietal P300 amplitude.
      Using curve-fitting methods, a comparison was made between the developmental
      trajectories of the amplitudes of the frontal and parietal P300. It was found
      that the developmental trajectories of frontal and parietal P300 amplitudes
      differed significantly across the lifespan. During adulthood, the amplitude of
      the parietal P300 declines with age, whereas both the frontal P300 amplitude and
      behavioral performance remain unaffected. A lifespan trajectory of combined
      frontal and parietal P300 amplitudes was found to closely resemble the lifespan
      trajectory of behavioral performance. Our results can be understood within the
      concepts of CRUNCH. That is, to compensate for declining neural resources, older
      participants recruit additional neural resources of prefrontal origin and
      consequently preserve a stable behavioral performance. Though, a direct relation
      between amplitude of the frontal P300 and compensatory mechanisms cannot yet be
      claimed. 

PMID- 25386142
TI  - The need for better AD animal models.

PMID- 25386144
TI  - Membrane nanotubes between peritoneal mesothelial cells: functional connectivity
      and crucial participation during inflammatory reactions.
AB  - Peritoneal dialysis (PD) has attained increased relevance as continuous renal
      replacement therapy over the past years. During this treatment, the peritoneum
      functions as dialysis membrane to eliminate diffusible waste products from the
      blood-stream. Success and efficacy of this treatment is dependent on the
      integrity of the peritoneal membrane. Chronic inflammatory conditions within the
      peritoneal cavity coincide with elevated levels of proinflammatory cytokines
      leading to the impairment of tissue integrity. High glucose concentrations and
      glucose metabolites in PD solutions contribute to structural and functional
      reorganization processes of the peritoneal membrane during long-term PD. The
      subsequent loss of ultrafiltration is causal for the treatment failure over time.
      It was shown that peritoneal mesothelial cells are functionally connected via
      Nanotubes (NTs) and that a correlation of NT-occurrence and defined
      pathophysiological conditions exists. Additionally, an important participation of
      NTs during inflammatory reactions was shown. Here, we will summarize recent
      developments of NT-related research and provide new insights into NT-mediated
      cellular interactions under physiological as well as pathophysiological
      conditions. 

PMID- 25386143
TI  - Interleukin-12 family cytokines and sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease predominantly affecting the
      lungs. It is believed to be caused by exposure to pathogenic antigens in
      genetically susceptible individuals but the causative antigen has not been
      identified. The formation of non-caseating granulomas at sites of ongoing
      inflammation is the key feature of the disease. Other aspects of the pathogenesis
      are peripheral T-cell anergy and disease progression to fibrosis. Many T-cell
      associated cytokines have been implicated in the immunopathogenesis of
      sarcoidosis, but it is becoming apparent that IL-12 cytokine family members
      including IL-12, IL-23, IL-27, and IL-35 are also involved. Although the members
      of this unique cytokine family are heterodimers of similar subunits, their
      biological functions are very diverse. Whilst IL-23 and IL-12 are pro
      inflammatory regulators of Th1 and Th17 responses, IL-27 is bidirectional for
      inflammation and the most recent family member IL-35 is inhibitory. This review
      will discuss the current understanding of etiology and immunopathogenesis of
      sarcoidosis with a specific focus on the bidirectional impact of IL-12 family
      cytokines on the pathogenesis of sarcoidosis. 

PMID- 25386145
TI  - Neuromodulation and cognitive rehabilitation: addressing the methodological issue
      of circadian rhythms.

PMID- 25386147
TI  - Impulsivity links reward and threat sensitivities to substance use: a functional
      model.
AB  - This study used structural equations modeling and undergraduate student data to
      examine the effects of reward and threat sensitivities on substance use, along
      with the extent to which impulsivity explained these effects. Our results suggest
      that impulsivity may translate inversely related reward and threat sensitivities
      into substance use, completely mediate the effect between threat sensitivity and
      substance use, and partially mediate the effect between reward sensitivity and
      substance use. Our results also suggest that individuals with a combination of
      higher levels on both reward and threat sensitivities may be most impulsive and
      vulnerable to heightened substance use. We discuss implications for research at
      the interface of personality and substance use and also substance abuse
      prevention and treatment. 

PMID- 25386148
TI  - A mind you can count on: validating breath counting as a behavioral measure of
      mindfulness.
AB  - Mindfulness practice of present moment awareness promises many benefits, but has
      eluded rigorous behavioral measurement. To date, research has relied on self
      reported mindfulness or heterogeneous mindfulness trainings to infer skillful
      mindfulness practice and its effects. In four independent studies with over 400
      total participants, we present the first construct validation of a behavioral
      measure of mindfulness, breath counting. We found it was reliable, correlated
      with self-reported mindfulness, differentiated long-term meditators from age
      matched controls, and was distinct from sustained attention and working memory
      measures. In addition, we employed breath counting to test the nomological
      network of mindfulness. As theorized, we found skill in breath counting
      associated with more meta-awareness, less mind wandering, better mood, and
      greater non-attachment (i.e., less attentional capture by distractors formerly
      paired with reward). We also found in a randomized online training study that 4
      weeks of breath counting training improved mindfulness and decreased mind
      wandering relative to working memory training and no training controls. Together,
      these findings provide the first evidence for breath counting as a behavioral
      measure of mindfulness. 

PMID- 25386146
TI  - Distributed processing of color and form in the visual cortex.
AB  - To what extent does the visual system process color and form separately?
      Proponents of the segregation view claim that distinct regions of the cortex are
      dedicated to each of these two dimensions separately. However, evidence is
      accumulating that color and form processing may, at least to some extent, be
      intertwined in the brain. In this perspective, we review psychophysical and
      neurophysiological studies on color and form perception and evaluate their
      results in light of recent developments in population coding. 

PMID- 25386149
TI  - Native-likeness in second language lexical categorization reflects individual
      language history and linguistic community norms.
AB  - SECOND LANGUAGE LEARNERS FACE A DUAL CHALLENGE IN VOCABULARY LEARNING: First,
      they must learn new names for the 100s of common objects that they encounter
      every day. Second, after some time, they discover that these names do not
      generalize according to the same rules used in their first language. Lexical
      categories frequently differ between languages (Malt et al., 1999), and
      successful language learning requires that bilinguals learn not just new words
      but new patterns for labeling objects. In the present study, Chinese learners of
      English with varying language histories and resident in two different language
      settings (Beijing, China and State College, PA, USA) named 67 photographs of
      common serving dishes (e.g., cups, plates, and bowls) in both Chinese and
      English. Participants' response patterns were quantified in terms of similarity
      to the responses of functionally monolingual native speakers of Chinese and
      English and showed the cross-language convergence previously observed in
      simultaneous bilinguals (Ameel et al., 2005). For English, bilinguals' names for
      each individual stimulus were also compared to the dominant name generated by the
      native speakers for the object. Using two statistical models, we disentangle the
      effects of several highly interactive variables from bilinguals' language
      histories and the naming norms of the native speaker community to predict inter
      personal and inter-item variation in L2 (English) native-likeness. We find only a
      modest age of earliest exposure effect on L2 category native-likeness, but
      importantly, we find that classroom instruction in L2 negatively impacts L2
      category native-likeness, even after significant immersion experience. We also
      identify a significant role of both L1 and L2 norms in bilinguals' L2 picture
      naming responses. 

PMID- 25386151
TI  - The Gratton effect remains after controlling for contingencies and stimulus
      repetitions.
AB  - HIGHLIGHTS: The conflict monitoring hypothesis signals the need for cognitive
      controlThe Gratton effect is a key result attributed to the conflict monitoring
      hypothesisSome argue that controlling binding confounds eliminates the Gratton
      effect A Gratton effect remains in a vocal Stroop task after eliminating
      confounds The Gratton effect, the observation that the size of the Stroop effect
      is larger following a congruent trial compared to an incongruent trial, is one
      pivotal observation in support of the conflict-monitoring hypothesis. Previous
      reports have demonstrated that non-conflict components, such as feature binding,
      also contribute to this effect. Critically, Schmidt and De Houwer (2011) report a
      flanker task and a button-press Stroop task suggesting that there is no conflict
      adaptation in the Gratton effect; it is entirely caused by feature binding. The
      current investigation attempts to replicate and extend this important finding
      across two experiments using a canonical four-choice Stroop task with vocal
      responses. In contrast to Schmidt and De Houwer, we observe reliable conflict
      adaptation after controlling for feature binding. We argue that the overall
      strength of conflict is critical for determining whether a conflict adaptation
      component will remain in the Gratton effect after explaining binding components.

PMID- 25386152
TI  - Creativity and psychopathology: are there similar mental processes involved in
      creativity and in psychosis-proneness?

PMID- 25386153
TI  - A comparison of two procedures for verbal response time fractionation.
AB  - To describe the mental architecture between stimulus and response, cognitive
      models often divide the stimulus-response (SR) interval into stages or modules.
      Predictions derived from such models are typically tested by focusing on the
      moment of response emission, through the analysis of response time (RT)
      distributions. To go beyond the single response event, we recently proposed a
      method to fractionate verbal RTs into two physiologically defined intervals that
      are assumed to reflect different processing stages. The analysis of the durations
      of these intervals can be used to study the interaction between cognitive and
      motor processing during speech production. Our method is inspired by studies on
      decision making that used manual responses, in which RTs were fractionated into a
      premotor time (PMT), assumed to reflect cognitive processing, and a motor time
      (MT), assumed to reflect motor processing. In these studies, surface EMG activity
      was recorded from participants' response fingers. EMG onsets, reflecting the
      initiation of a motor response, were used as the point of fractionation. We
      adapted this method to speech-production research by measuring verbal responses
      in combination with EMG activity from facial muscles involved in articulation.
      However, in contrast to button-press tasks, the complex task of producing speech
      often resulted in multiple EMG bursts within the SR interval. This observation
      forced us to decide how to operationalize the point of fractionation: as the
      first EMG burst after stimulus onset (the stimulus-locked approach), or as the
      EMG burst that is coupled to the vocal response (the response-locked approach).
      The point of fractionation has direct consequences on how much of the overall
      task effect is captured by either interval. Therefore, the purpose of the current
      paper was to compare both onset-detection procedures in order to make an informed
      decision about which of the two is preferable. We concluded in favor or the
      response-locked approach. 

PMID- 25386154
TI  - Reading enjoyment amongst non-leisure readers can affect achievement in secondary
      school.
AB  - This study aimed to evaluate determinants of differences in leisure reading
      behavior and school achievement. We specifically examined reading enjoyment,
      mental imagery, and sex as predictors in a large, age-homogeneous sample of Dutch
      secondary school students (N = 1,071). Results showed that the prevalence of
      leisure reading was low in both the lower, pre-vocational track (19.5%) and the
      higher, pre-academic track (32.5%). Boys read even less than girls. Almost all
      leisure readers enjoyed reading and engaged in mental imagery, i.e., the
      propensity "to see images" of a written story in the mind's eye. Overall, boys
      who did not like to read for leisure had the poorest school performance. Non
      leisure readers who reported that they enjoyed reading got higher school grades
      in the higher educational track. In the lower track, this was the case for girls.
      Our study findings imply that reading promotion programs should take into account
      individual differences in sex, achievement level, and reading enjoyment when
      aiming to decrease the academic achievement gap. 

PMID- 25386155
TI  - Mechanisms of white matter change induced by meditation training.
AB  - Training can induce changes in specific brain networks and changes in brain
      state. In both cases it has been found that the efficiency of white matter as
      measured by diffusion tensor imaging is increased, often after only a few hours
      of training. In this paper we consider a plausible molecular mechanism for how
      state change produced by meditation might lead to white matter change. According
      to this hypothesis frontal theta induced by meditation produces a molecular
      cascade that increases myelin and improves connectivity. 

PMID- 25386150
TI  - Controversies about a common etiology for eating and mood disorders.
AB  - Obesity and depression represent a growing health concern worldwide. For many
      years, basic science and medicine have considered obesity as a metabolic illness,
      while depression was classified a psychiatric disorder. Despite accumulating
      evidence suggesting that obesity and depression may share commonalities, the
      causal link between eating and mood disorders remains to be fully understood.
      This etiology is highly complex, consisting of multiple environmental and genetic
      risk factors that interact with each other. In this review, we sought to
      summarize the preclinical and clinical evidence supporting a common etiology for
      eating and mood disorders, with a particular emphasis on signaling pathways
      involved in the maintenance of energy balance and mood stability, among which
      orexigenic and anorexigenic neuropeptides, metabolic factors, stress responsive
      hormones, cytokines, and neurotrophic factors. 

PMID- 25386156
TI  - Chiari 1 Malformation Presenting as Central Sleep Apnea during Pregnancy: A Case
      Report, Treatment Considerations, and Review of the Literature.
AB  - PURPOSE: Chiari malformation (CM) type-1 frequently causes obstructive or central
      sleep-disordered breathing (SDB) in both adults and children, although SDB is
      relatively rare as a presenting manifestation in the absence of other
      neurological symptoms. The definitive treatment of symptomatic CM is surgical
      decompression. We report a case that is, to our knowledge, a novel manifestation
      of central sleep apnea (CSA) due to CM type-1 with severe exacerbation and
      initial clinical presentation during pregnancy. METHODS: Case report from
      tertiary care comprehensive sleep medicine center with literature review of SDB
      manifestations associated with CM type-1. PubMed search was conducted between
      January 1982 and October 2013. RESULTS: We report a 25-year-old woman with severe
      CSA initially presenting during her first pregnancy that eventually proved to be
      caused by CM type-1. The patient was successfully treated preoperatively by
      adaptive servoventilation (ASV), with effective resolution of SDB following
      surgical decompression, and without recurrence in a subsequent pregnancy. Our
      literature review found that 58% of CM patients with SDB had OSA alone, 28% had
      CSA alone, 8 (10%) had mixed OSA/CSA, and 6 (8%) had hypoventilation. Of CM
      patients presenting with SDB, 50% had OSA, 42% had CSA, 8% had mixed OSA/CSA, and
      10.4% had hypoventilation. We speculate that CSA may develop in CM patients in
      whom brainstem compression results in excessive central chemoreflex sensitivity
      with consequent hypocapnic CSA. CONCLUSION: Chiari malformation type-1 may
      present with a diversity of SDB manifestations, and timely recognition and
      surgical referral are necessary to prevent further neurological deficits. ASV
      therapy can effectively manage CSA caused by CM type-1, which may initially
      present during pregnancy.

PMID- 25386158
TI  - Why industry propaganda and political interference cannot disguise the inevitable
      role played by human exposure to aluminum in neurodegenerative diseases,
      including Alzheimer's disease.
AB  - In the aluminum age, it is clearly unpalatable for aluminum, the globe's most
      successful metal, to be implicated in human disease. It is unpalatable because
      for approximately 100 years human beings have reaped the rewards of the most
      abundant metal of the Earth's crust without seriously considering the potential
      consequences for human health. The aluminum industry is a pillar of the developed
      and developing world and irrespective of the tyranny of human exposure to
      aluminum it cannot be challenged without significant consequences for businesses,
      economies, and governments. However, no matter how deep the dependency or
      unthinkable the withdrawal, science continues to document, if not too slowly, a
      burgeoning body burden of aluminum in human beings. Herein, I will make the case
      that it is inevitable both today and in the future that an individual's exposure
      to aluminum is impacting upon their health and is already contributing to, if not
      causing, chronic diseases such as Alzheimer's disease. This is the logical, if
      uncomfortable, consequence of living in the aluminum age. 

PMID- 25386159
TI  - Subjective cognitive fatigue in multiple sclerosis depends on task length.
AB  - OBJECTIVE: The objective of this paper is to investigate the interrelationship
      between subjective and objective cognitive fatigue, information processing domain
      [processing speed (PS) vs. working memory (WM)], cognitive load (high vs. low),
      and time on task in Multiple Sclerosis (MS). METHODS: Thirty-two MS participants
      and 24 healthy controls completed experimental tasks in both the PS and WM
      domains with different levels of cognitive load. Subjective cognitive fatigue was
      measured using a visual analog scale at baseline and at multiple time points
      throughout the experiment. RESULTS: A mixed model ANOVA revealed that subjective
      cognitive fatigue was higher for the PS task, increased across time, and was
      higher in the MS group. These findings were qualified by an interaction
      demonstrating that the MS group showed a steeper increase in subjective cognitive
      fatigue over time than the healthy control group. Subjective and objective (i.e.,
      performance) cognitive fatigue were not correlated. CONCLUSION: In this study,
      subjective and objective cognitive fatigue appears to be independent and
      cognitive fatigue does not depend on cognitive load. Subjective cognitive fatigue
      increased with time on task and subjective cognitive fatigue increased more
      steeply for the MS group. These data suggest that cognitive fatigue in MS is a
      function of time, that is, the longer participants were engaged in a cognitive
      task, the more likely it was for them to report increases in cognitive fatigue.

PMID- 25386160
TI  - The dynamics of the epileptic brain reveal long-memory processes.
AB  - The pattern of epileptic seizures is often considered unpredictable and the
      interval between events without correlation. A number of studies have examined
      the possibility that seizure activity respects a power-law relationship, both in
      terms of event magnitude and inter-event intervals. Such relationships are found
      in a variety of natural and man-made systems, such as earthquakes or Internet
      traffic, and describe the relationship between the magnitude of an event and the
      number of events. We postulated that human inter-seizure intervals would follow a
      power-law relationship, and furthermore that evidence for the existence of a long
      memory process could be established in this relationship. We performed a post hoc
      analysis, studying eight patients who had long-term (up to 2 years) ambulatory
      intracranial EEG data recorded as part of the assessment of a novel seizure
      prediction device. We demonstrated that a power-law relationship could be
      established in these patients (beta = - 1.5). In five out of the six subjects
      whose data were sufficiently stationary for analysis, we found evidence of long
      memory between epileptic events. This memory spans time scales from 30 min to 40
      days. The estimated Hurst exponents range from 0.51 to 0.77 +/- 0.01. This
      finding may provide evidence of phase-transitions underlying the dynamics of
      epilepsy. 

PMID- 25386161
TI  - A new model for secondary prevention of stroke: transition coaching for stroke.
AB  - Non-adherence to stroke prevention medications is a risk factor for first-ever
      and recurrent stroke. As of yet, there are no guidelines for processes to
      recognize and address medication non-adherence in stroke patients. We developed a
      new model of post-discharge prevention care that measures and addresses
      medication-taking (transition coaching for stroke or TRACS). TRACS includes
      personalized education about risk factors and medications prior to discharge,
      follow-up telephone calls, and appointments with a stroke nurse practitioner
      (NP). The stroke NP asks about medication use (persistence) and whether doses are
      missed (adherence), and helps to solve problems with access to medications or
      side effects. In an analysis of 142 patients enrolled in TRACS from October 2012
      to February 2014, medication persistence (use of medications from discharge to
      the time of measurement) was about 80%. Medication persistence at NP visit was
      higher in those patients with a first-ever stroke (78.9%) vs. those with
      recurrent stroke (60.7%; p = 0.045). Concerted efforts with 2-day RN follow-up
      calls and earlier NP appointments to improve medication-taking behaviors are
      underway. 

PMID- 25386162
TI  - Predicting cognitive decline in Parkinson's disease: can we ask the genes?

PMID- 25386157
TI  - Central gain control in tinnitus and hyperacusis.
AB  - Sensorineural hearing loss induced by noise or ototoxic drug exposure reduces the
      neural activity transmitted from the cochlea to the central auditory system.
      Despite a reduced cochlear output, neural activity from more central auditory
      structures is paradoxically enhanced at suprathreshold intensities. This
      compensatory increase in the central auditory activity in response to the loss of
      sensory input is referred to as central gain enhancement. Enhanced central gain
      is hypothesized to be a potential mechanism that gives rise to hyperacusis and
      tinnitus, two debilitating auditory perceptual disorders that afflict millions of
      individuals. This review will examine the evidence for gain enhancement in the
      central auditory system in response to cochlear damage. Further, it will address
      the potential cellular and molecular mechanisms underlying this enhancement and
      discuss the contribution of central gain enhancement to tinnitus and hyperacusis.
      Current evidence suggests that multiple mechanisms with distinct temporal and
      spectral profiles are likely to contribute to central gain enhancement.
      Dissecting the contributions of these different mechanisms at different levels of
      the central auditory system is essential for elucidating the role of central gain
      enhancement in tinnitus and hyperacusis and, most importantly, the development of
      novel treatments for these disorders. 

PMID- 25386164
TI  - Bariatric surgery and non-alcoholic Fatty liver disease: current and potential
      future treatments.
AB  - Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis
      (NASH) are increasingly common cause of chronic liver disease worldwide. The
      diagnosis of NASH is challenging as most affected patients are symptom-free and
      the role of routine screening is not clearly established. Most patients with
      severe obesity who undergo bariatric surgery have NAFLD, which is associated
      insulin resistance, type 2 diabetes mellitus (T2DM), hypertension, and obesity
      related dyslipidemia. The effective treatment for NAFLD is weight reduction
      through lifestyle modifications, antiobesity medication, or bariatric surgery.
      Among these treatments, bariatric surgery is the most reliable method for
      achieving substantial, sustained weight loss. This procedure is safe when
      performed by a skilled surgeon, and the benefits include reduced weight, improved
      quality of life, decreased obesity-related comorbidities, and increased life
      expectancy. Further research is urgently needed to determine the best use of
      bariatric surgery with NAFLD patients at high risk of developing liver cirrhosis
      and its role in modulating complications of NAFLD, such as T2DM and
      cardiovascular disease. The current evidence suggests that bariatric surgery for
      patients with severe obesity decreases the grade of steatosis, hepatic
      inflammation, and fibrosis. However, further long-term studies are required to
      confirm the true effects before recommending bariatric surgery as a potential
      treatment for NASH. 

PMID- 25386163
TI  - Ghrelin-Derived Peptides: A Link between Appetite/Reward, GH Axis, and
      Psychiatric Disorders?
AB  - Psychiatric disorders are often associated with metabolic and hormonal
      alterations, including obesity, diabetes, metabolic syndrome as well as
      modifications in several biological rhythms including appetite, stress, sleep
      wake cycles, and secretion of their corresponding endocrine regulators. Among the
      gastrointestinal hormones that regulate appetite and adapt the metabolism in
      response to nutritional, hedonic, and emotional dysfunctions, at the interface
      between endocrine, metabolic, and psychiatric disorders, ghrelin plays a unique
      role as the only one increasing appetite. The secretion of ghrelin is altered in
      several psychiatric disorders (anorexia, schizophrenia) as well as in metabolic
      disorders (obesity) and in animal models in response to emotional triggers
      (psychological stress ...) but the relationship between these modifications and
      the physiopathology of psychiatric disorders remains unclear. Recently, a large
      literature showed that this key metabolic/endocrine regulator is involved in
      stress and reward-oriented behaviors and regulates anxiety and mood. In addition,
      preproghrelin is a complex prohormone but the roles of the other ghrelin-derived
      peptides, thought to act as functional ghrelin antagonists, are largely unknown.
      Altered ghrelin secretion and/or signaling in psychiatric diseases are thought to
      participate in altered appetite, hedonic response and reward. Whether this can
      contribute to the mechanism responsible for the development of the disease or can
      help to minimize some symptoms associated with these psychiatric disorders is
      discussed in the present review. We will thus describe (1) the biological actions
      of ghrelin and ghrelin-derived peptides on food and drugs reward, anxiety and
      depression, and the physiological consequences of ghrelin invalidation on these
      parameters, (2) how ghrelin and ghrelin-derived peptides are regulated in animal
      models of psychiatric diseases and in human psychiatric disorders in relation
      with the GH axis. 

PMID- 25386165
TI  - Structural and functional divergence of gonadotropin-inhibitory hormone from
      jawless fish to mammals.
AB  - Gonadotropin-inhibitory hormone (GnIH) was discovered as a novel hypothalamic
      peptide that inhibits gonadotropin release in the quail. The presence of GnIH
      homologous peptides and its receptors (GnIHRs) have been demonstrated in various
      vertebrate species including teleosts, suggesting that the GnIH-GnIHR family is
      evolutionarily conserved. In avian and mammalian brain, GnIH neurons are
      localized in the hypothalamic nuclei and their neural projections are widely
      distributed. GnIH acts on the pituitary and gonadotropin-releasing hormone
      neurons to inhibit reproductive functions by decreasing gonadotropin release and
      synthesis. In addition, GnIH-GnIHR signaling is regulated by various factors,
      such as environmental cues and stress. However, the function of fish GnIH
      orthologs remains inconclusive because the physiological properties of fish GnIH
      peptides are debatable. This review summarizes the current research progress in
      GnIH-GnIHR signaling and their physiological functions in vertebrates with
      special emphasis on non-mammalian vertebrate species. 

PMID- 25386167
TI  - Three Decades of Research on O-GlcNAcylation - A Major Nutrient Sensor That
      Regulates Signaling, Transcription and Cellular Metabolism.
AB  - Even though the dynamic modification of polypeptides by the monosaccharide, O
      linked N-acetylglucosamine (O-GlcNAcylation) was discovered over 30 years ago,
      its physiological significance as a major nutrient sensor that regulates myriad
      cellular processes has only recently been more widely appreciated. O
      GlcNAcylation, either on its own or by its interplay with other post
      translational modifications, such as phosphorylation, ubiquitination, and others,
      modulates the activities of signaling proteins, regulates most components of the
      transcription machinery, affects cell cycle progression and regulates the
      targeting/turnover or functions of myriad other regulatory proteins, in response
      to nutrients. Acute increases in O-GlcNAcylation protect cells from stress
      induced injury, while chronic deregulation of O-GlcNAc cycling contributes to the
      etiology of major human diseases of aging, such as diabetes, cancer, and
      neurodegeneration. Recent advances in tools to study O-GlcNAcylation at the
      individual site level and specific inhibitors of O-GlcNAc cycling have allowed
      more rapid progress toward elucidating the specific functions of O-GlcNAcylation
      in essential cellular processes. 

PMID- 25386166
TI  - Diversity of the RFamide Peptide Family in Mollusks.
AB  - Since the initial characterization of the cardioexcitatory peptide FMRFamide in
      the bivalve mollusk Macrocallista nimbosa, a great number of FMRFamide-like
      peptides (FLPs) have been identified in mollusks. FLPs were initially isolated
      and molecularly characterized in model mollusks using biochemical methods. The
      development of recombinant technologies and, more recently, of genomics has
      boosted knowledge on their diversity in various mollusk classes. Today, mollusk
      FLPs represent approximately 75 distinct RFamide peptides that appear to result
      from the expression of only five genes: the FMRFamide-related peptide gene, the
      LFRFamide gene, the luqin gene, the neuropeptide F gene, and the
      cholecystokinin/sulfakinin gene. FLPs display a complex spatiotemporal pattern of
      expression in the central and peripheral nervous system. Working as
      neurotransmitters, neuromodulators, or neurohormones, FLPs are involved in the
      control of a great variety of biological and physiological processes including
      cardiovascular regulation, osmoregulation, reproduction, digestion, and feeding
      behavior. From an evolutionary viewpoint, the major challenge will then logically
      concern the elucidation of the FLP repertoire of orphan mollusk classes and the
      way they are functionally related. In this respect, deciphering FLP signaling
      pathways by characterizing the specific receptors these peptides bind remains
      another exciting objective. 

PMID- 25386168
TI  - Free Fatty acids and their metabolism affect function and survival of podocytes.
AB  - Podocyte injury and loss critically contribute to the pathogenesis of proteinuric
      kidney diseases including diabetic nephropathy. Deregulated lipid metabolism with
      disturbed free fatty acid (FFA) metabolism is a characteristic of metabolically
      unhealthy obesity and type 2 diabetes and likely contributes to end-stage kidney
      disease irrespective of the underlying kidney disease. In the current review, we
      summarize recent findings related to FFAs and altered renal FFA metabolism with a
      special focus on podocytes. We will outline the opposing effects of saturated and
      monounsaturated FFAs and a particular emphasis will be given to the underlying
      molecular mechanisms involving insulin resistance and endoplasmic reticulum
      homeostasis. Finally, recent data suggesting a critical role of renal FFA
      metabolism to adapt to an altered lipid environment will be discussed. 

PMID- 25386170
TI  - The microbial nitrogen cycle.

PMID- 25386169
TI  - Perturbations in small molecule synthesis uncovers an iron-responsive secondary
      metabolite network in Aspergillus fumigatus.
AB  - Iron plays a critical role in survival and virulence of the opportunistic
      pathogen Aspergillus fumigatus. Two transcription factors, the GATA-factor SreA
      and the bZip-factor HapX oppositely monitor iron homeostasis with HapX activating
      iron acquisition pathways (e.g., siderophores) and shutting down iron consumptive
      pathways (and SreA) during iron starvation conditions whereas SreA negatively
      regulates HapX and corresponding pathways during iron sufficiency. Recently the
      non-ribosomal peptide, hexadehydroastechrome (HAS; a tryptophan-derived iron
      (III)-complex), has been found important in A. fumigatus virulence. We found that
      HAS overproduction caused an iron starvation phenotype, from alteration of
      siderophore pools to regulation of iron homeostasis gene expression including
      sreA. Moreover, we uncovered an iron dependent secondary metabolism network where
      both SreA and HapX oppositely regulate multiple other secondary metabolites
      including HAS. This circuitry links iron-acquisition and consumption pathways
      with secondary metabolism-thus placing HAS as part of a metabolic feedback
      circuitry designed to balance iron pools in the fungus and presenting iron
      availability as one environmental trigger of secondary metabolism. 

PMID- 25386172
TI  - The emerging role of dendritic cells in the host immune response against
      Helicobacter pylori.

PMID- 25386171
TI  - Physiological levels of nitrate support anoxic growth by denitrification of
      Pseudomonas aeruginosa at growth rates reported in cystic fibrosis lungs and
      sputum.
AB  - Chronic Pseudomonas aeruginosa lung infection is the most severe complication in
      patients with cystic fibrosis (CF). The infection is characterized by the
      formation of biofilm surrounded by numerous polymorphonuclear leukocytes (PMNs)
      and strong O2 depletion in the endobronchial mucus. We have reported that O2 is
      mainly consumed by the activated PMNs, while O2 consumption by aerobic
      respiration is diminutive and nitrous oxide (N2O) is produced in infected CF
      sputum. This suggests that the reported growth rates of P. aeruginosa in lungs
      and sputum may result from anaerobic respiration using denitrification. The
      growth rate of P. aeruginosa achieved by denitrification at physiological levels
      (~400 MUM) of nitrate (NO(-) 3) is however, not known. Therefore, we have
      measured growth rates of anoxic cultures of PAO1 and clinical isolates (n = 12)
      in LB media supplemented with NO(-) 3 and found a significant increase of growth
      when supplementing PAO1 and clinical isolates with >=150 MUM NO(-) 3 and 100 MUM
      NO(-) 3, respectively. An essential contribution to growth by denitrification was
      demonstrated by the inability to establish a significantly increased growth rate
      by a denitrification deficient DeltanirS-N mutant at <1 mM of NO(-) 3. Activation
      of denitrification could be achieved by supplementation with as little as 62.5
      MUM of NO(-) 3 according to the significant production of N2O by the nitrous
      oxide reductase deficient DeltanosZ mutant. Studies of the promoter activity,
      gene transcripts, and enzyme activity of the four N-oxide reductases in PAO1
      (Nar, Nir, Nor, Nos) further verified the engagement of denitrification, showing
      a transient increase in activation and expression and rapid consumption of NO(-)
      3 followed by a transient increase of NO(-) 2. Growth rates obtained by
      denitrification in this study were comparable to our reported growth rates in the
      majority of P. aeruginosa cells in CF lungs and sputum. Thus, we have
      demonstrated that denitrification is required for P. aeruginosa growth in
      infected endobronchial CF mucus. 

PMID- 25386173
TI  - The discovery of T cell-B cell cooperation.

PMID- 25386174
TI  - Eosinophil secretion of granule-derived cytokines.
AB  - Eosinophils are tissue-dwelling leukocytes, present in the thymus, and
      gastrointestinal and genitourinary tracts of healthy individuals at baseline, and
      recruited, often in large numbers, to allergic inflammatory foci and sites of
      active tissue repair. The biological significance of eosinophils is vast and
      varied. In health, eosinophils support uterine and mammary gland development, and
      maintain bone marrow plasma cells and adipose tissue alternatively activated
      macrophages, while in response to tissue insult eosinophils function as
      inflammatory effector cells, and, in the wake of an inflammatory response,
      promote tissue regeneration, and wound healing. One common mechanism driving many
      of the diverse eosinophil functions is the regulated and differential secretion
      of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished
      from most other leukocytes in that many, if not all, of the over three dozen
      eosinophil-derived cytokines are pre-synthesized and stored within intracellular
      granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged
      in cytokine secretion in situ utilize distinct pathways of cytokine release that
      include classical exocytosis, whereby granules themselves fuse with the plasma
      membrane and release their entire contents extracellularly; piecemeal
      degranulation, whereby granule-derived cytokines are selectively mobilized into
      vesicles that emerge from granules, traverse the cytoplasm and fuse with the
      plasma membrane to release discrete packets of cytokines; and eosinophil
      cytolysis, whereby intact granules are extruded from eosinophils, and deposited
      within tissues. In this latter scenario, extracellular granules can themselves
      function as stimulus-responsive secretory-competent organelles within the tissue.
      Here, we review the distinctive processes of differential secretion of eosinophil
      granule-derived cytokines. 

PMID- 25386176
TI  - Immunoglobulin Free Light Chains and GAGs Mediate Multiple Myeloma Extracellular
      Vesicles Uptake and Secondary NfkappaB Nuclear Translocation.
AB  - Multiple myeloma (MM) is a hematological malignancy caused by a
      microenviromentally aided persistence of plasma cells in the bone marrow.
      Monoclonal plasma cells often secrete high amounts of immunoglobulin free light
      chains (FLCs) that could induce tissue damage. Recently, we showed that FLCs are
      internalized in endothelial and myocardial cell lines and secreted in
      extracellular vesicles (EVs). MM serum derived EVs presented phenotypic
      differences if compared with monoclonal gammopathy of undetermined significance
      (MGUS) serum derived EVs suggesting their involvement in MM pathogenesis or
      progression. To investigate the effect of circulating EVs on endothelial and
      myocardial cells, we purified MM and MGUS serum derived EVs with differential
      ultracentrifugation protocols and tested their biological activity. We found that
      MM and MGUS EVs induced different proliferation and internalization rates in
      endothelial and myocardial cells, thus we tried to find specific targets in MM
      EVs docking and processing. Pre-treatment of EVs with anti-FLCs antibodies or
      heparin blocked the MM EVs uptake, highlighting that FLCs and glycosaminoglycans
      are involved. Indeed, only MM EVs exposure induced a strong nuclear factor kappa
      B nuclear translocation that was completely abolished after anti-FLCs antibodies
      and heparin pre-treatment. The protein tyrosine kinase c-src is present on MM
      circulating EVs and redistributes to the cell plasma membrane after MM EVs
      exposure. The anti-FLCs antibodies and heparin pre-treatments were able to block
      the intracellular re-distribution of the c-src kinase and the subsequent c-src
      kinase containing EVs production. Our results open new insights in EVs cellular
      biology and in MM therapeutic and diagnostic approaches. 

PMID- 25386177
TI  - Evolution of the serendipitous discovery of macrophage-lymphocyte interactions.

PMID- 25386175
TI  - Complex adaptive immunity to enteric fevers in humans: lessons learned and the
      path forward.
AB  - Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid
      fever, and S. Paratyphi A and B, causative agents of paratyphoid fever, are major
      public health threats throughout the world. Although two licensed typhoid
      vaccines are currently available, they are only moderately protective and
      immunogenic necessitating the development of novel vaccines. A major obstacle in
      the development of improved typhoid, as well as paratyphoid vaccines is the lack
      of known immunological correlates of protection in humans. Considerable progress
      has been made in recent years in understanding the complex adaptive host
      responses against S. Typhi. Although the induction of S. Typhi-specific
      antibodies (including their functional properties) and memory B cells, as well as
      their cross-reactivity with S. Paratyphi A and S. Paratyphi B has been shown, the
      role of humoral immunity in protection remains undefined. Cell mediated immunity
      (CMI) is likely to play a dominant role in protection against enteric fever
      pathogens. Detailed measurements of CMI performed in volunteers immunized with
      attenuated strains of S. Typhi have shown, among others, the induction of
      lymphoproliferation, multifunctional type 1 cytokine production, and CD8(+)
      cytotoxic T-cell responses. In addition to systemic responses, the local
      microenvironment of the gut is likely to be of paramount importance in protection
      from these infections. In this review, we will critically assess current
      knowledge regarding the role of CMI and humoral immunity following natural S.
      Typhi and S. Paratyphi infections, experimental challenge, and immunization in
      humans. We will also address recent advances regarding cross-talk between the
      host's gut microbiota and immunization with attenuated S. Typhi, mechanisms of
      systemic immune responses, and the homing potential of S. Typhi-specific B- and T
      cells to the gut and other tissues. 

PMID- 25386178
TI  - Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways
      in Macrophages.
AB  - Macrophages play a major role in the immune system, both as antimicrobial
      effector cells and as immunoregulatory cells, which induce, suppress or modulate
      adaptive immune responses. These key aspects of macrophage biology are
      fundamentally driven by the phenotype of macrophage arginine metabolism that is
      prevalent in an evolving or ongoing immune response. M1 macrophages express the
      enzyme nitric oxide synthase, which metabolizes arginine to nitric oxide (NO) and
      citrulline. NO can be metabolized to further downstream reactive nitrogen
      species, while citrulline might be reused for efficient NO synthesis via the
      citrulline-NO cycle. M2 macrophages are characterized by expression of the enzyme
      arginase, which hydrolyzes arginine to ornithine and urea. The arginase pathway
      limits arginine availability for NO synthesis and ornithine itself can further
      feed into the important downstream pathways of polyamine and proline syntheses,
      which are important for cellular proliferation and tissue repair. M1 versus M2
      polarization leads to opposing outcomes of inflammatory reactions, but depending
      on the context, M1 and M2 macrophages can be both pro- and anti-inflammatory.
      Notably, M1/M2 macrophage polarization can be driven by microbial infection or
      innate danger signals without any influence of adaptive immune cells, secondarily
      driving the T helper (Th)1/Th2 polarization of the evolving adaptive immune
      response. Since both arginine metabolic pathways cross-inhibit each other on the
      level of the respective arginine break-down products and Th1 and Th2 lymphocytes
      can drive or amplify macrophage M1/M2 dichotomy via cytokine activation, this
      forms the basis of a self-sustaining M1/M2 polarization of the whole immune
      response. Understanding the arginine metabolism of M1/M2 macrophage phenotypes is
      therefore central to find new possibilities to manipulate immune responses in
      infection, autoimmune diseases, chronic inflammatory conditions, and cancer. 

PMID- 25386179
TI  - Functions of arginase isoforms in macrophage inflammatory responses: impact on
      cardiovascular diseases and metabolic disorders.
AB  - Macrophages play a paramount role in immunity and inflammation-associated
      diseases, including infections, cardiovascular diseases, obesity-associated
      metabolic imbalances, and cancer. Compelling evidence from studies of recent
      years demonstrates that macrophages are heterogeneous and undergo heterogeneous
      phenotypic changes in response to microenvironmental stimuli. The M1 killer type
      response and the M2 repair type response are best known, and are two extreme
      examples. Among other markers, inducible nitric oxide synthase and type-I
      arginase (Arg-I), the enzymes that are involved in l-arginine/nitric oxide (NO)
      metabolism, are associated with the M1 and M2 phenotype, respectively, and
      therefore widely used as the markers for characterization of the two macrophage
      phenotypes. There is also a type-II arginase (Arg-II), which is expressed in
      macrophages and prevalently viewed as having the same function as Arg-I in the
      cells. In contrast to Arg-I, little information on the role of Arg-II in
      macrophage inflammatory responses is available. Emerging evidence, however,
      suggests that differential roles of Arg-I and Arg-II in regulating macrophage
      functions. In this article, we will review recent developments on the functional
      roles of the two arginase isoforms in regulation of macrophage inflammatory
      responses by focusing on their impact on the pathogenesis of cardiovascular
      diseases and metabolic disorders. 

PMID- 25386182
TI  - Unraveling the repertoire in wiskott-Aldrich syndrome.

PMID- 25386181
TI  - Cytokine Secretion in Macrophages: SNAREs, Rabs, and Membrane Trafficking.
AB  - Macrophages have the capacity to rapidly secrete a wide range of inflammatory
      mediators that influence the development and extent of an inflammatory response.
      Newly synthesized and/or preformed stored cytokines and other inflammatory
      mediators are released upon stimulation, the timing, and volume of which is
      highly regulated. To finely tune this process, secretion is regulated at many
      levels; at the level of transcription and translation and post-translationally at
      the endoplasmic reticulum (ER), Golgi, and at or near the cell surface. Here, we
      discuss recent advances in deciphering these cytokine pathways in macrophages,
      focusing on recent discoveries regarding the cellular machinery and mechanisms
      implicated in the synthesis, trafficking, and secretion of cytokines. The
      specific roles of trafficking machinery including chaperones, GTPases,
      cytoskeletal proteins, and SNARE membrane fusion proteins will be discussed. 

PMID- 25386183
TI  - Association between CTL Precursor Frequency to HLA-C Mismatches and HLA-C Antigen
      Cell Surface Expression.
AB  - Previous studies showed the relevance of the cytotoxic T-cell precursor (CTLp)
      frequency assay for prediction of the outcome of HLA mismatched hematopoietic
      cell transplantation (HCT). Recently, it has been shown that HLA-C cell surface
      expression is correlated with virus specific cytotoxic T-cell responses and
      viremia control in HIV patients. The aim of the current study was to investigate
      the association between HLA-C antigen expression and the CTLp frequency to the
      mismatched HLA-C antigen. In total 115 recipient-donor pairs, for whom a
      successful CTLp assay was performed, were evaluated for this pilot study. All
      donor-recipient pairs were matched at 9/10 alleles with a single mismatch at the
      HLA-C locus. Antigen expression level of the mismatched HLA-C allele for each
      recipient and donor was based on the mean fluorescence intensity (MFI) values as
      described by Apps et al. (1). The cell surface expression of recipient's
      mismatched HLA-C antigen was significantly lower among CTLp negative (n = 59)
      compared to CTLp positive (n = 56) pairs (154 and 193 MFI units, respectively, p
      = 0.0031). This difference was more pronounced in donor-recipient pairs that were
      mismatched for amino-acid residue-116 located in the groove of the HLA-C antigen,
      suggesting that the importance of peptide binding in the allo-recognition.
      Furthermore, in the particular case of low expression of the recipient mismatched
      HLA-C antigen (MFI < 115), CTLp reactivity depended on HLA-C expression level in
      the donor, the median MFI of donor's mismatched HLA-C antigen was 114 in CTLp
      negative cases (n = 26), while in CTLp positive cases (n = 15) the median MFI of
      donor's HLA-C antigen was 193 (p = 0.0093). We conclude that the expression level
      of the donor and recipient mismatched HLA-C antigens affect CTLp outcome. HLA-C
      antigen expression levels in combination with the CTLp assay may prove useful for
      the prediction of the clinical outcome of HLA-C mismatched HCT. 

PMID- 25386184
TI  - Newly identified helper bacteria stimulate ectomycorrhizal formation in Populus.
AB  - Mycorrhiza helper bacteria (MHB) are known to increase host root colonization by
      mycorrhizal fungi but the molecular mechanisms and potential tripartite
      interactions are poorly understood. Through an effort to study Populus
      microbiome, we isolated 21 Pseudomonas strains from native Populus deltoides
      roots. These bacterial isolates were characterized and screened for MHB
      effectiveness on the Populus-Laccaria system. Two additional Pseudomonas strains
      (i.e., Pf-5 and BBc6R8) from existing collections were included for comparative
      purposes. We analyzed the effect of co-cultivation of these 23 individual
      Pseudomonas strains on Laccaria bicolor "S238N" growth rate, mycelial
      architecture and transcriptional changes. Nineteen of the 23 Pseudomonas strains
      tested had positive effects on L. bicolor S238N growth, as well as on mycelial
      architecture, with strains GM41 and GM18 having the most significant effect. Four
      of seven L. bicolor reporter genes, Tra1, Tectonin2, Gcn5, and Cipc1, thought to
      be regulated during the interaction with MHB strain BBc6R8, were induced or
      repressed, while interacting with Pseudomonas strains GM17, GM33, GM41, GM48, Pf
      5, and BBc6R8. Strain GM41 promoted the highest roots colonization across three
      Populus species but most notably in P. deltoides, which is otherwise poorly
      colonized by L. bicolor. Here we report novel MHB strains isolated from native
      Populus that improve L. bicolor root colonization on Populus. This tripartite
      relationship could be exploited for Populus species/genotypes nursery production
      as a means of improving establishment and survival in marginal lands. 

PMID- 25386185
TI  - Mycobacterium ulcerans Disease with Unusual Sites Not to Be Ignored.
AB  - Objective. The usual preferential site of BU is in the limbs. In our experience,
      we noticed atypical and often misleading sites which pose serious issues for the
      diagnosis and often for the treatment. Methods. This is a retrospective study
      conducted over a period of ten years of BU treatment at the Department of
      Dermatology of the University Teaching Hospital of Treichville (Abidjan, Cote
      d'Ivoire). We included in this study all BU cases with atypical site diagnosed
      clinically and confirmed either by the histology, by smear, or by PCR. Results.
      Epidemiologically, the age of patients ranged from 3 to 72 years with a median
      age of 14.2 years. Children aged less than 15 years were affected in almost 80%
      of case. The clinical table was dominated by ulcerated forms in 82.1% of cases.
      The unusual topography mostly observed was that of the torso (thorax, back, and
      abdomen) in 76.8% of cases. Conclusion. BU is an endemic disease in Cote d'Ivoire
      where it constitutes a serious public health issue. Several years following its
      first cases, BU still is little known. This dermatosis may present atypical
      misleading clinical aspects which must be ignored. 

PMID- 25386180
TI  - The Role of the Immune Response in Chlamydia trachomatis Infection of the Male
      Genital Tract: A Double-Edged Sword.
AB  - Chlamydia trachomatis (CT) is the most prevalent bacterial sexually transmitted
      infection in the world, with more than 100 million cases reported annually. While
      there have been extensive studies into the adverse effects that CT infection has
      on the female genital tract, and on the subsequent ability of these women to
      conceive, studies into the consequences on male fertility have been limited and
      controversial. This is in part due to the asymptomatic nature of the infection,
      where it is estimated that 50% of men with Chlamydia fail to show any symptoms.
      It is accepted, however, that acute and/or persistent CT infection is the
      causative agent for conditions such as urethritis, epididymitis, epididymo
      orchitis, and potentially prostatitis. As with most infections, the immune system
      plays a fundamental role in the body's attempts to eradicate the infection. The
      first and most important immune response to Chlamydia infection is a local one,
      whereby immune cells such as leukocytes are recruited to the site of infections,
      and subsequently secrete pro-inflammatory cytokines and chemokines such as
      interferon gamma. Immune cells also work to initiate and potentiate chronic
      inflammation through the production of reactive oxygen species (ROS), and the
      release of molecules with degradative properties including defensins, elastase,
      collagenase, cathespins, and lysozyme. This long-term inflammation can lead to
      cell proliferation (a possible precursor to cancer), tissue remodeling, and
      scarring, as well as being linked to the onset of autoimmune responses in
      genetically disposed individuals. This review will focus on the ability of the
      immune system to recognize and clear acute and persistent chlamydial infections
      in the male genital tract, and on the paradoxical damage that chronic
      inflammation resulting from the infection can cause on the reproductive health of
      the individual. 

PMID- 25386186
TI  - Prevention and treatment of esophageal stenosis after endoscopic submucosal
      dissection for early esophageal cancer.
AB  - Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal
      lesions is associated with a risk of esophageal stenosis, especially for near
      circumferential or circumferential esophageal mucosal defects. Here, we review
      historic and modern studies on the prevention and treatment of esophageal
      stenosis after ESD. These methods include prevention via pharmacological
      treatment, endoscopic autologous cell transplantation, endoscopic esophageal
      dilatation, and stent placement. This short review will focus on direct
      prevention and treatment, which may help guide the way forward. 

PMID- 25386188
TI  - Lipid Profile and Oxidative Stress Markers in Wistar Rats following Oral and
      Repeated Exposure to Fijk Herbal Mixture.
AB  - This study determined the effect of the oral and repeated administration of Fijk
      herbal mixture on rat biochemical and morphological parameters. Twenty-four
      Wistar rats were distributed into four groups of 6. Group A served as control and
      received oral administration of distilled water daily. The experimental groups B,
      C, and D were daily and orally exposed to Fijk herbal mixture at 15, 30, and 45
      mg/kg, respectively. Treatments lasted for 21 days. The rats were sacrificed
      under mild diethyl ether anesthesia 24 hr after cessation of treatment. The blood
      and liver samples were collected and used for the biochemical and morphological
      analyses. Oral exposure to Fijk caused elevated levels of rat plasma ALT, AST,
      triglycerides, LDL, and MDA. In contrast, rat plasma HDL, GSH, and ALP levels
      were lowered by Fijk oral exposure. Also, the herbal remedy caused a dose
      dependent elevation in the plasma atherogenic index. The histopathology
      examinations of rat liver sections revealed inimical cellular alterations caused
      by repeated exposure to Fijk. Study provides evidence that oral and repeated
      exposure to Fijk in rats raised the atherogenic index and potentiated oxidative
      stress as well as hepatic injury. 

PMID- 25386187
TI  - Epidemiology characteristics of constipation for general population, pediatric
      population, and elderly population in china.
AB  - Objective. To acquire more data about the epidemiologic characteristics of
      constipation in different kinds of populations in China. Methods. Using
      "constipation" and "China" as search terms; relevant papers were searched from
      January 1995 to April 2014. Data on prevalence, gender, diagnostic criteria,
      geographical area, educational class, age, race, and physician visit results were
      extracted and analyzed. Results. 36 trials were included. Prevalence rates of
      constipation in elderly population (18.1%) and pediatric population (18.8%) were
      significantly higher than that in general population (8.2%). Prevalence of
      constipation defined by non-Rome criteria was higher than that by Rome criteria
      in general population. Prevalence rates of constipation were different for
      different geographical area. People with less education were predisposed to
      constipation. In pediatric population, prevalence of constipation was the lowest
      in children aged 2-6 years. Prevalence of constipation in ethnic minorities was
      higher than that in Han people. People with constipation were predisposed to FD,
      haemorrhoid, and GERD. Only 22.2% patients seek medical advice in general
      population. Conclusions. In China, prevalence of constipation was lower compared
      with most of other countries. The factors including female gender, diagnostic
      criteria, geographical area, age, educational class, and race seemed to have
      major effects on prevalence of constipation. 

PMID- 25386189
TI  - Association of ATM Gene Polymorphism with PTC Metastasis in Female Patients.
AB  - Ataxia telangiectasia mutated (ATM) gene is critical in the process of
      recognizing and repairing DNA lesions and is related to invasion and metastasis
      of malignancy. The incidence rate of papillary thyroid cancer (PTC) has increased
      for several decades and is higher in females than males. In this study, we want
      to investigate whether ATM polymorphisms are associated with gender-specific
      metastasis of PTC. 358 PTC patients in Northern China, including 109 males and
      249 females, were included in our study. Four ATM single nucleotide polymorphisms
      (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of
      Flight Mass Spectrometry (MALDI-TOF-MS). Association between genotypes and the
      gender-specific risk of metastasis was assessed by odds ratios (OR) and 95%
      confidence intervals (CI) under the unconditional logistic regression analysis.
      Significant associations were observed between rs189037 and metastasis of PTC in
      females under different models of inheritance (codominant model: OR = 0.15, 95%
      CI 0.04-0.56, P = 0.01 for GA versus GG and OR = 0.08, 95% CI 0.01-0.74, P = 0.03
      for AA versus GG, resp.; dominant model: OR = 0.49, 95% CI 0.25-0.98, P = 0.04;
      overdominant model: OR = 0.47, 95% CI 0.25-0.89, P = 0.02). However, no
      association remained significant after Bonferroni correction. Our findings
      suggest a possible association between ATM rs189037 polymorphisms and metastasis
      in female PTCs. 

PMID- 25386190
TI  - Pretransplant HbA1c Is a Useful Predictor for the Development of New-Onset
      Diabetes in Renal Transplant Recipients Receiving No or Low-Dose Erythropoietin.
AB  - Aims. To evaluate the predictive power of pretransplant HbA1c for new-onset
      diabetes after transplantation (NODAT) in kidney transplant candidates, who had
      several predispositions for fluctuated HbA1c levels. Methods. We performed a
      retrospective study of 119 patients without diabetes who received kidney
      transplantation between March 2000 and January 2012. Univariate and multivariate
      logistic regression analyses were used to investigate the association of several
      parameters with NODAT. Predictive discrimination of HbA1c was assessed using a
      receiver-operating characteristic curve. Results. Seventeen patients (14.3%)
      developed NODAT within 1 year of transplantation. Univariate logistic regression
      analysis revealed that recipient age, gender, and HbA1c were predictors of NODAT.
      In the multivariate analysis, the association between pretransplant HbA1c and
      NODAT development did not reach statistical significance (P = 0.07). To avoid the
      strong influence of high-dose erythropoietin on HbA1c levels, we performed
      subgroup analyses on 85 patients receiving no or low-dose (<=6000 IU/week)
      erythropoietin. HbA1c was again an independent predictor for NODAT. Receiver
      operating characteristic analysis revealed a cut-off value of 5.2% with an
      optimal sensitivity of 64% and specificity of 78% for predicting NODAT.
      Conclusions. Our results reveal that the pretransplant HbA1c level is a useful
      predictor for NODAT in patients receiving no or low-dose erythropoietin. 

PMID- 25386191
TI  - A Porous TiAl6V4 Implant Material for Medical Application.
AB  - Increased durability of permanent TiAl6V4 implants still remains a requirement
      for the patient's well-being. One way to achieve a better bone-material
      connection is to enable bone "ingrowth" into the implant. Therefore, a new porous
      TiAl6V4 material was produced via metal injection moulding (MIM). Specimens with
      four different porosities were produced using gas-atomised spherical TiAl6V4 with
      different powder particle diameters, namely, "Small" (<45 MUm), "Medium" (45-63
      MUm), "Mix" (90% 125-180 MUm + 10% <45 MUm), and "Large" (125-180 MUm). Tensile
      tests, compression tests, and resonant ultrasound spectroscopy (RUS) were used to
      analyse mechanical properties. These tests revealed an increasing Young's modulus
      with decreasing porosity; that is, "Large" and "Mix" exhibit mechanical
      properties closer to bone than to bulk material. By applying X-ray tomography (3D
      volume) and optical metallographic methods (2D volume and dimensions) the pores
      were dissected. The pore analysis of the "Mix" and "Large" samples showed pore
      volumes between 29% and 34%, respectively, with pore diameters ranging up to 175
      MUm and even above 200 MUm for "Large." Material cytotoxicity on bone cell lines
      (SaOs-2 and MG-63) and primary cells (human bone-derived cells, HBDC) was studied
      by MTT assays and highlighted an increasing viability with higher porosity. 

PMID- 25386192
TI  - Prevalence and Specificity of RBC Alloantibodies in Indian Patients Attending a
      Tertiary Care Hospital.
AB  - Background. Red blood cell (RBC) alloimmunization results from genetic disparity
      of RBC antigens between donor and recipients. Data about alloimmunization rate in
      general patient population is scarce especially from resource limited countries.
      We undertook this study to determine prevalence and specificity of RBC
      alloantibodies in patients admitted in various clinical specialties at a tertiary
      care hospital in North India. Methods. Antibody screening was carried out in
      11,235 patients on automated QWALYS 3 platform (Diagast, Loos, France). Antibody
      identification was carried out with an 11-cell identification panel (ID-Diapanel,
      Diamed GmbH, Switzerland). Results. The overall incidence of RBC alloimmunization
      in transfused patients was 1.4% (157/11235), with anti-E being the most common
      specificity (36.3%), followed by anti-D (16%), anti-c (6.4%), anti-c + E (6.4%),
      anti-C + D (5.1%), and anti-K (4.5%). The highest incidence of alloimmunization
      was observed in hematology/oncology patients (1.9%), whereas in other specialties
      the range was 0.7-1%. Conclusion. As alloimmunization complicates the transfusion
      outcomes, authors recommend pretransfusion antibody screening and issue of Rh and
      Kell matched blood to patients who warrant high transfusion requirements in
      future. 

PMID- 25386193
TI  - Clinical and autoimmune profile of scleroderma patients from Western India.
AB  - Background. Systemic sclerosis (SSc, scleroderma) is a disorder characterized by
      fibrosis of skin and visceral organs. Pathogenesis of scleroderma is complex and
      is incompletely understood as yet. Autoantibodies in SSc represent a serologic
      hallmark which have clinical relevance, with diagnostic and prognostic potential.
      Objectives. To study distribution of clinical manifestations and to identify
      frequency of autoantibodies among subtypes of scleroderma patients from Western
      India. Methodology. One hundred and ten scleroderma patients were clinically
      classified according to the American College of Rheumatology/European League
      Against Rheumatism (ACR/EULAR) criteria. All these patients were in active stage
      of disease. Clinical manifestations were recorded at the time of presentation.
      Autoantibodies were tested in them by indirect immunofluorescence test and ELISA.
      Immunoglobulin levels were estimated by nephelometer. These parameters were
      further correlated with clinical presentation of the disease. Results.
      Scleroderma patients had M : F ratio of 1 : 10 where mean age at evaluation was
      34.7 +/- 10.7 years and a mean disease duration was 43.7 +/- 35 months. Clinical
      subtypes showed that 45 patients (40.9%) had diffused cutaneous (dcSSc) lesions,
      32 patients (29.1%) had limited cutaneous (lcSSc) lesions, and 33 patients (30%)
      had other autoimmune overlaps. The overall frequency of ANA in SSc patients
      studied was 85.5%. The frequency of anti-Scl70, anti-centromere, anti-endothelial
      cell antibodies (AECA), and anti-keratinocyte antibodies (AKA) was 62.7%, 22.7%,
      30%, and 40.9%, respectively. Anti-Scl70 antibodies were significantly high
      (75.6% versus 46.9%) among dcSSc patients (P < 0.0115) whereas anti-centromere
      antibodies were significantly high (9% versus 38%) among lcSSc patients when
      these two subtypes were compared (P < 0.0044). Conclusion. This study supports
      that there are geoepidemiological variations among scleroderma patients for their
      clinical presentation, autoantibody profile, and immune parameters across the
      country. 

PMID- 25386194
TI  - Coexisting mantle cell lymphoma and prostate adenocarcinoma.
AB  - Prostatic mantle cell lymphoma (MCL) is a very rare entity with only 5 reported
      cases in the literature. We report a case of coexisting MCL and prostate
      adenocarcinoma (PCa) in an elderly male and review the morphologic features of
      classic and rare prostatic MCL subtypes. Careful morphologic evaluation and
      immunohistochemical findings of positive CD5, CD20, and cyclin D1 and negative
      CD23 and CD3 can guide us to the diagnosis of MCL. Given the fact that
      transurethral resection of prostate is done quite routinely, this paper draws
      attention to the manner in which long standing bladder outlet obstruction and
      postbiopsy prostate specimens with dense lymphoid infiltration can masquerade as
      lymphoma. It highlights the importance of exercising care while reviewing
      prostate specimens with evidence of chronic prostatitis so as not to miss this
      rare neoplasm. 

PMID- 25386195
TI  - Femoral Nerve Palsy due to Anticoagulant Induced Retroperitoneal Hematoma.
AB  - A forty-one-year-old man who, sought evaluation for a sudden hip flexion
      contracture and groin pain with a history of mechanical mitral valve replacement,
      had been misdiagnosed and treated as having lumbar discopathy for two days. This
      patient finally was diagnosed with compressive femoral neuropathy due to warfarin
      induced retroperitoneal hematoma and successfully managed nonoperatively. This
      case is reported in order to draw attention to this rare presentation. 

PMID- 25386196
TI  - Takotsubo's Cardiomyopathy in a Patient with Kartagener's Syndrome.
AB  - A 46-year-old African-American male with past medical history significant for
      Kartagener's syndrome, essential hypertension, and HIV presented with acute chest
      pain. ECG and troponins indicated an acute myocardial infarction.
      Ventriculography confirmed dyskinesia of the left ventricle, with an EF of 25%.
      However the coronary catheterization showed nonobstructed coronaries. Ventricular
      contraction and EF were restored in 4 weeks. To our knowledge, this is the first
      incidence of Takotsubo's reported in a young patient with Kartagener's syndrome.
      Chronic lung disease may contribute to the development of Takotsubo's
      cardiomyopathy, which is a documented yet not fully understood phenomenon. 

PMID- 25386197
TI  - Diagnostic Value of Serum Level of Soluble Tumor Necrosis Factor Receptor IIalpha
      in Egyptian Patients With Chronic Hepatitis C Virus Infection and Hepatocellular
      Carcinoma.
AB  - BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is unfavorable and
      needs serum markers that could detect it early to start therapy at a potentially
      curable phase. OBJECTIVES: The aim of this study was to determine the value of
      serum soluble tumor necrosis factor (TNF) receptor-IIalpha (sTNFR-IIalpha) in
      diagnosis of HCC in patients with chronic hepatitis C virus (HCV) infection.
      PATIENTS AND METHODS: The study was performed on 110 subjects who were classified
      into five groups. Group I included 20 patients with chronic noncirrhotic HCV
      infection and persistently normal transaminases for >=6 months. Group II included
      20 patients with chronic noncirrhotic HCV infection and elevated transaminases.
      Group III included 20 patients with Chronic HCV infection and liver cirrhosis.
      Group IV included 20 patients with chronic HCV infection with liver cirrhosis and
      HCC. Group V included 30 healthy age and sex-matched controls. Medical history
      was taken from all participants and they underwent clinical examination and
      abdominal ultrasonography. in addition, the following laboratory tests were
      requested: liver function tests, complete blood count, HBsAg, anti-HCVAb, HCV-RNA
      by qualitative PCR, and serum levels of alpha-fetoprotein (AFP) and sTNFR
      IIalpha. RESULTS: The serum level of sTNFR-IIalpha was significantly higher in
      patients with HCC in comparison to the other groups. A positive correlation was
      found between the serum levels of sTNFR-IIalpha and AST and ALT in patients of
      group-II. Diagnosis of HCC among patients with HCV infection and cirrhosis could
      be ascertained when sTNFR-IIalpha is assessed at a cutoff value of >= 250 pg/mL.
      CONCLUSIONS: Serum sTNFR-IIalpha could be used as a potential serum marker in
      diagnosing HCC among patients with HCV infection.

PMID- 25386198
TI  - An unusual cause for a hepatic flare in a chronic HBV carrier.
AB  - INTRODUCTION: Hepatitis E is an emerging disease in developed countries with an
      increasing incidence. In developed countries, HEV genotype 3 prevails as a
      zoonotic disease carried by wild boars or pigs, which usually causes asymptomatic
      infection. CASE PRESENTATION: An asymptomatic HBsAg carrier was tested regularly
      at a German university hospital and showed no signs of chronic hepatitis B (CHB)
      activity. At a routine visit, elevated aminotransferases were detected while HBV
      DNA remained low and the patient was clinically asymptomatic. The laboratory
      signs of acute hepatitis resolved spontaneously. When aminotransferases returned
      to normal limits, the patient showed a flare of HBV-replication, which resolved
      spontaneously. In follow-up, further investigations revealed a resolved hepatitis
      E (HEV) superinfection causing an acute hepatitis before the HBV flare. No
      potential risk factors for HEV infection were identified. CONCLUSIONS: Elevated
      aminotransferases in CHB patients are most commonly caused by exacerbation of
      CHB. Nevertheless, when HBV DNA is not elevated, other reasons should be
      excluded. Amongst others, superinfection with another hepatotropic virus can be
      the reason for decompensation of chronic hepatitis B. This case report describes
      an asymptomatic HEV superinfection followed by a flare in HBV replication in an
      HBsAg carrier without signs of HBV replication for eight years. In CHB carriers
      with signs of acute hepatitis, rare causes should be considered as well. HEV
      should be a part of routine laboratory evaluation for hepatitis flares given the
      rising number of infections.

PMID- 25386199
TI  - Analytical assessment of interleukin - 23 and -27 cytokines in healthy people and
      patients with hepatitis C virus infection (genotypes 1 and 3a).
AB  - BACKGROUND: The immune system plays important roles in determining the outcomes
      of hepatitis C virus (HCV) infection. Interleukin-23 and -27 (IL-23 and IL-27)
      are two novel IL-12 cytokine family members known to enhance the T-lymphocyte
      response, but their precise involvement in HCV infection is not well known.
      OBJECTIVES: We investigated the serum IL-27 and IL-23 levels in patients with HCV
      infection and in healthy individuals. PATIENTS AND METHODS: In this case-control
      study, we assessed IL-23 and IL-27 levels in serum of 37 healthy individuals and
      64 patients with chronic HCV using Enzyme-linked immunosorbent assay (ELISA). The
      relationship of cytokines level with liver enzymes (ALT, AST, and ALP), HCV
      genotype and viral load were analyzed. The differences of these cytokine levels
      in the groups of treatment and no treatment was compared. HCV genotypes were
      classified by HCV-specific primers methods. HCV RNA loads were determined by
      fluorescence quantitative PCR. RESULTS: Serum level of IL-23 was higher in HCV
      infected patients compared to control group (P = 0.005). However, no significant
      difference was seen in IL-27 serum level between patients compared to the control
      group (P = 0.65). There was no significant difference in IL-23 and IL-27 level
      between genotype 1 HCV-infected- and 3a HCV-infected- patients. Positive moderate
      correlation between IL-23 and IL-27 with viral load was found in type 3a and 1
      HCV-infected patient. Positive relative correlation was seen between ALT and IL
      23 in 1a HCV-infected patients, which was higher than 3a HCV-infected patients;
      but there were no significant difference between serums liver enzymes with IL-23
      and IL-27 in respect to genotype 3a and 1a HCV-infected patients. CONCLUSIONS:
      These findings may reflect a vigorous pro-inflammatory reaction orchestrated by
      the host immune system against chronic HCV. Also, a better understanding of the
      involvement mechanism considering the correlation between other genotypes with
      inflammatory cytokines in various stages of disease can be obtained.

PMID- 25386201
TI  - A Review of the Various Surface Treatments of NiTi Instruments.
AB  - Since the introduction of engine-driven nickel-titanium (NiTi) instruments,
      attempts have been made to minimize or eliminate their inherent defects, increase
      their surface hardness/flexibility and also improve their resistance to cyclic
      fatigue and cutting efficiency. The various strategies of enhancing instrument
      surface include ion implantation, thermal nitridation, cryogenic treatment and
      electropolishing. The purpose of this paper was to review the metallurgy and
      crystal characteristics of NiTi alloy and to present a general over review of the
      published articles on surface treatment of NiTi endodontic instruments. 

PMID- 25386202
TI  - Accuracy of conventional and digital radiography in detecting external root
      resorption.
AB  - INTRODUCTION: External root resorption (ERR) is associated with physiological and
      pathological dissolution of mineralized tissues by clastic cells and radiography
      is one of the most important methods in its diagnosis. The aim of this
      experimental study was to evaluate the accuracy of conventional intraoral
      radiography (CR) in comparison with digital radiographic techniques, i.e. charge
      coupled device (CCD) and photo-stimulable phosphor (PSP) sensors, in detection of
      ERR. METHODS AND MATERIALS: This study was performed on 80 extracted human
      mandibular premolars. After taking separate initial periapical radiographs with
      CR technique, CCD and PSP sensors, the artificial defects resembling ERR with
      variable sizes were created in apical half of the mesial, distal and buccal
      surfaces of the teeth. Ten teeth were used as control samples without any
      resorption. The radiographs were then repeated with 2 different exposure times
      and the images were observed by 3 observers. Data were analyzed using SPSS
      version 17 and chi-squared and Cohen's Kappa tests with 95% confidence interval
      (CI=95%). RESULT: The CCD had the highest percentage of correct assessment
      compared to the CR and PSP sensors, although the difference was not significant
      (P=0.39). It was shown that the higher dosage of radiation increases the accuracy
      of diagnosis; however, it was only significant for CCD sensor (P=0.02). Also, the
      accuracy of diagnosis increased with the increase in the size of lesion
      (P=0.001). CONCLUSION: Statistically significant difference was not observed for
      accurate detection of ERR by conventional and digital radiographic techniques.

PMID- 25386203
TI  - Push-Out Bond Strength of Dorifill, Epiphany and MTA-Fillapex Sealers to Root
      Canal Dentin with and without Smear Layer.
AB  - INTRODUCTION: The aim of the present experimental study was to evaluate the push
      out bond strength of Dorifill, Epiphany and MTA-Fillapex sealers to root canal
      dentin in presence and absence of smear layer (SL). METHODS AND MATERIALS: Sixty
      human single-rooted teeth were selected and divided into six groups (n=10). The
      canal irrigation protocol in groups 1, 3 and 5 consisted of 2.5% NaOCl during
      instrumentation and normal saline at the end of preparation plus a 5-min
      irrigation with 17% ethylenediaminetetraacetic acid (EDTA). In the remaining
      groups, normal saline was used for canal irrigation. The root canals were filled
      with Epiphany/Resilon (groups 1 and 2), Dorifill/gutta-percha (groups 3 and 4)
      and MTA-Fillapex/gutta-percha (groups 5 and 6). After two weeks of storage in 95%
      relative humidity at 37(o)C, 2 mm-thick dentin disks were prepared from coronal
      third of each root. The push-out bond strength test was carried out using a
      universal testing machine. Data were analyzed with the two-way ANOVA and post hoc
      Tukey's tests. Statistical significance was defined at 0.05. RESULTS: The highest
      (3.06+/-0.38 MPa) and lowest (1.16+/-0.32 MPa) push-out bond strength values were
      recorded in Epiphany/Resilon-NaOCl/EDTA and Dorifill/gutta-percha/normal saline
      groups, respectively. There were significant differences in the bond strength of
      sealers (P<0.05). In addition, elimination of the SL significantly increased the
      bond strength of all sealers (P<0.05). CONCLUSION: The Epiphany/Resilon group
      exhibited the highest push-out bond strength in the presence and absence of the
      SL. Elimination of the SL resulted in a significant increase in the bond strength
      of all the sealers to dentin.

PMID- 25386204
TI  - General Dental Practitioners' Knowledge about the Emergency Management of Dental
      Trauma.
AB  - INTRODUCTION: The aim of this descriptive cross-sectional study was to assess the
      general dental practitioners (GDPs)'s knowledge regarding the emergency
      management of traumatic dental injuries (TDI) in Isfahan, Iran. METHODS AND
      MATERIALS: In this study a two-part questionnaire consisting of 14 questions was
      distributed among 241 GDPs. Part 1 included seven questions focusing on personal
      and professional information and part 2 asked questions about seven given cases
      of dental traumas. One score was dedicated to each correct answer; the total
      score of 0 to 4 was considered as poor knowledge, while scores 5-8, 9-11 and 12
      14 were assigned as moderate, good and excellent knowledge, respectively. The
      data were analyzed using the Student's t-test and one-way ANOVA. Spearman's and
      Pearson's correlation coefficient were used to determine the associations between
      the emergency treatment knowledge and dentists' professional information.
      RESULTS: With regards to the level of GDP's knowledge, the mean score was 7.61+/
      2.68 suggesting a moderate score; a total of 177 (73.2%) of the dentists showed a
      moderate level of knowledge. A significant association was found between the
      frequency of dental trauma cases that were encountered and treated by GDPs in
      their daily practice (P=0.004, r=0.2). CONCLUSION: The overall knowledge of GDPs
      about the emergency management of TDI in the selected community was moderate.

PMID- 25386205
TI  - The Effect of Acidic pH on Microleakage of Mineral Trioxide Aggregate and Calcium
      Enriched Mixture Apical Plugs.
AB  - INTRODUCTION: The purpose of this laboratory study was to evaluate the effect of
      acidic pH on the sealing ability of calcium-enriched mixture (CEM) cement and
      mineral trioxide aggregate (MTA) apical plugs. METHODS AND MATERIALS: Seventy
      single-rooted human maxillary anterior teeth were recruited. The teeth were
      randomly divided into 4 experimental groups (n=15), and 1 negative and 1 positive
      control groups of 5. The root canals were cleaned and shaped and the terminal 3
      mm of the roots were resected. Then MTA and CEM cement plugs were condensed in
      apical region with 3 mm thicknesses. The samples were exposed to pH values of 5.5
      and 7.4. Leakage was evaluated by the fluid filtration technique at 1, 7, 14, 30
      day intervals. Data were analyzed by the repeated measures MANOVA, one-way ANOVA
      and MANOVA/Bonferroni test. RESULTS: Acidic pH significantly reduced the sealing
      ability of MTA after 1, 14 and 30 days (P<0.05). The rate of microleakage in CEM
      cement samples in acidic pH was significantly greater than that in neutral pH in
      day 30 (P<0.05). There was no significant difference between the sealing property
      of MTA and CEM cement at both pH levels (P>0.05). CONCLUSION: It can be concluded
      that the CEM cement exhibited similar sealing ability as MTA at both pH levels.
      In addition, an acidic pH environment reduced the sealing ability of MTA and CEM
      cement after 30 days.

PMID- 25386206
TI  - Sealing ability of mineral trioxide aggregate and calcium-enriched mixture cement
      as apical barriers with different obturation techniques.
AB  - INTRODUCTION: Endodontic treatment in pulpless immature teeth is challenging due
      to the lack of an apical stop. Insertion of an apical plug is an alternative to
      conventional long-term apexification with calcium hydroxide. The aim of this
      study was to compare the apical microleakage of mineral trioxide aggregate (MTA)
      and calcium-enriched mixture (CEM) cement as apical plugs with three different
      obturation techniques. METHODS AND MATERIALS: This experimental study was
      conducted on 130 single rooted human teeth with one canal. Samples were randomly
      divided into 2 experimental groups (n=60) and two negative and positive control
      groups containing 5 samples each. After cleaning and shaping, an open apex
      configuration was prepared in all samples. MTA or CEM cement apical plugs with 5
      mm thicknesses were placed. Then, each group was divided to 4 subgroups and the
      remaining space of root canals were filled with either lateral compaction or
      thermoplasticized injectable gutta-percha or was obturated by filling the entire
      canal with apical plug material. In one remaining subgroup the canal space was
      left unfilled. Microleakage was measured by the fluid filtration method and
      results were analyzed by means of the two-way ANOVA test. RESULTS: There were no
      significant differences between microleakage of MTA and CEM cement apical plugs
      (P=0.92). The difference between three obturation methods was not significant,
      either (P=0.39). CONCLUSION: MTA and CEM cement have similar sealing ability as
      apical plugs and no significant difference was found in microleakage of the three
      groups.

PMID- 25386207
TI  - Effect of acidic environment on the push-out bond strength of calcium-enriched
      mixture cement.
AB  - INTRODUCTION: This laboratory study was performed to evaluate the effect of
      different acidic pH values on the push-out bond strength of calcium-enriched
      mixture (CEM) cement. METHODS AND MATERIALS: Forty-eight root dentin slices were
      obtained from freshly extracted single rooted human teeth and their lumen were
      instrumented to achieve a diameter of 1.3 mm. Then, CEM cement was mixed
      according to manufacturers' instruction and placed in the lumens with minimal
      pressure. The specimens were randomly divided into four groups (n=12) which were
      wrapped in pieces of gauze soaked in either synthetic tissue fluid (STF) (pH=7.4)
      or butyric acid which was buffered at pH values of 4.4, 5.4 and 6.4. They were
      then incubated for 4 days at 37 degrees C. The push-out test was performed by
      means of the universal testing machine. Specimens were then examined under a
      digital light microscope at 20* magnification to determine the nature of the bond
      failure. The data were analyzed using the Kruskal-Wallis test followed by Dunn's
      test for pairwise comparisons. RESULTS: The highest push-out bond strength
      (10.19+/-4.39) was seen in the pH level of 6.4, which was significantly different
      from the other groups (P<0.05). The values decreased to 2.42+/-2.25 MPa after
      exposure to pH value of 4.4. CONCLUSION: Lower pH value of highly acidic
      environments (pH=4.4), adversely affects the force needed for displacement of CEM
      cement; while in higher pH values (pH=6.4) the bond-strength was not affected.
      CEM cement is recommended in clinical situations where exposure to acidic
      environment is unavoidable.

PMID- 25386208
TI  - Cytotoxic effects of various mineral trioxide aggregate formulations, calcium
      enriched mixture and a new cement on human pulp stem cells.
AB  - INTRODUCTION: This in vitro study compared the cytotoxic effects of three
      commercially available MTA formulations naming ProRoot MTA (PMTA), Angelus MTA
      (AMTA), and Root MTA (RMTA), with calcium-enriched mixture (CEM) cement and a new
      nanohybrid MTA (NMTA) on human dental pulp stem cells (DPSC). METHODS AND
      MATERIALS: Four disc-shaped specimens of each material were prepared. After
      completion of setting, 2 different (neat and 1/2) elutes of the test materials
      were made. Then in each cavity of a 96-well plate, 3000 cells were seeded and
      incubated in a humidified incubator with 5% CO2 and 95% air at 37( degrees )C for
      24 h. After this period, the culture medium of each well was replaced with 200
      MUL of test material elutes. Plain culture medium was used as the negative
      control and distilled water as the positive control group. Cell viability was
      assessed using 2, 5-diphenyl-SH-tetrazelium bromide colorimetric assay, aka
      Mosmann's tetrazolium toxicity (MTT) assay, at three time intervals (24, 48, and
      72 h after mixing). Data were analyzed using the ANOVA and Tukey's post hoc test
      (P=0.05). RESULTS: After 24 h, the viability of cells in neat concentration had
      no significant differences (P>0.05) except for the NMTA. However, CEM and AMTA,
      at 1/2 concentration exerted significant proliferative effects on cells. At 48
      and 72-h intervals, significant proliferation of DPSCs was seen in all samples,
      except for the NMTA which exerted toxic effects on cells. CONCLUSION: All of the
      three commercial MTAs and CEM cement showed comparative biocompatibility.
      However, NMTA had cytotoxic effects on DPSCs at all the time intervals.

PMID- 25386209
TI  - General Dental Practitioners' Concept towards Using Radiography and Apex-Locators
      in Endodontics.
AB  - INTRODUCTION: Despite being the gold standard as well as a routine technique in
      endodontics, radiographic working length (WL) determination owns many drawbacks.
      Electronic apex-locators (EALs) are recommended to complement radiographies. The
      aim of this study was to evaluate the perceptions of Iranian general dental
      practitioners (GDPs) towards using radiography and EAL. METHODS AND MATERIALS:
      Three hundred and ninety one GDPs attending the 53(th) Iranian Dental Association
      Congress completed a questionnaire focusing on the use of radiography and EALs
      during the various stages of root canal treatment. The data was analyzed with the
      chi-square test with the level of significance set at 0.05. The results were then
      calculated as frequencies and percentages. RESULTS: More than half of the GDPs
      reported using radiographs as the sole method for WL determination. A total of
      30.4% of the practitioners were using the combined approach during root canal
      therapy of a single-rooted tooth, while 38.9% used this method in multi-rooted
      teeth. Approximately half of the respondents would not order follow-up
      radiographies after root canal treatment. CONCLUSION: Radiography continues to be
      the most common method for WL determination in Iran.

PMID- 25386210
TI  - Comparison of CT-Number and Gray Scale Value of Different Dental Materials and
      Hard Tissues in CT and CBCT.
AB  - INTRODUCTION: Computed tomography (CT) and cone-beam CT (CBCT) are valuable
      diagnostic aids for many clinical applications. This study was designed to
      compare the gray scale value (GSV) and Hounsfield unit (HU) of selected dental
      materials and various hard tissues using CT or CBCT. METHODS AND MATERIALS: Three
      samples of all test materials including amalgam (AM), composite resin (CR), glass
      ionomer (GI), zinc-oxide eugenol (ZOE), calcium-enriched mixture (CEM) cement, AH
      26 root canal sealer (AH-26), gutta-percha (GP), Coltosol (Col), Dycal (DL),
      mineral trioxide aggregate (MTA), zinc phosphate (ZP), and polycarbonate cement
      (PC) were prepared and scanned together with samples of bone, dentin and enamel
      using two CBCT devices, Scanora 3D (S3D) and NewTom VGi (NTV) and a spiral CT
      (SCT) scanner (Somatom Emotion 16 multislice spiral CT);. Subsequently, the HU
      and GSV values were determined and evaluated. The data were analyzed by the
      Kruskal-Wallis and Mann-Whitney U tests. The level of significance was determined
      at 0.05. RESULTS: There were significant differences among the three different
      scanners (P<0.05). The differences between HU/GSV values of 12 selected dental
      materials using NTV was significant (P<0.05) and for S3D and SCT was
      insignificant (P>0.05). All tested materials showed maximum values in S3D and SCT
      (3094 and 3071, respectively); however, bone and dentin showed low/medium values
      (P<0.05). In contrast, the tested materials and tissues showed a range of values
      in NTV (366 to15383; P<0.05). CONCLUSION: Scanner system can influence the
      obtained HU/GSV of dental materials. NTV can discriminate various dental
      materials, in contrast to S3D/SCT scanners. NTV may be a more useful diagnostic
      aid for clinical practice.

PMID- 25386211
TI  - An in vitro comparison of the antibacterial efficacy of triphala with different
      concentrations of sodium hypochlorite.
AB  - INTRODUCTION: The antimicrobial efficacy of root canal irrigant plays an
      important role in increasing the success of root canal treatment (RCT). The aim
      of the present experimental study was to compare the antimicrobial activity of
      Triphala (a plant-derived solution) with 0.5, 1, 2.5 and 5% concentrations of
      sodium hypochlorite (NaOCl), against Enterococcus faecalis (E. faecalis). METHODS
      AND MATERIALS: Two hundred plates of cultured E. faecalis, were divided into 5
      experimental groups (n=38) and two positive and negative control groups. The
      antimicrobial activity of the test solutions was determined by measuring the zone
      of inhibition in the culture media. The mean diameter of inhibited zones between
      the study groups was compared using the Kruskal-Wallis test and the Mann-Whitney
      U test was used for the two-by-two comparison of the groups with the level of
      significance set at 0.05. RESULTS: The Kruskal-Wallis test showed significant
      differences between the study groups (P<0.05). According to the Mann-Whitney U
      test the mean diameter of inhibition zones in Triphala group was significantly
      higher compared to 0.5 and 1% NaOCl (P<0.05). CONCLUSION: In this study, Triphala
      exhibited better antimicrobial activity against E. faecalis compared to 0.5 and
      1% NaOCl (P<0.05).

PMID- 25386212
TI  - The effect of adding fentanyl to epinephrine-containing lidocaine on the
      anesthesia of maxillary teeth with irreversible pulpitis: a randomized clinical
      trial.
AB  - INTRODUCTION: Deep and long-lasting anesthesia is essential throughout endodontic
      treatment. This study was conducted to compare the effect of adding fentanyl to
      epinephrine-containing lidocaine on depth and duration of local anesthesia in
      painful maxillary molars with irreversible pulpitis (IRP). METHODS AND MATERIALS:
      This randomized double-blind, clinical trial with parallel design was conducted
      on 61 healthy volunteers; the control group received a mixture of normal saline
      and 2% lidocaine with 1:80000 epinephrine and the experimental group received a
      mixture of fentanyl and 2% lidocaine with 1:80000 epinephrine. The depth and
      duration of pulpal anesthesia were evaluated by means of electric pulp testing in
      5-min intervals during a period of 60 min. Pain intensity was recorded five
      times: before injection, after injection, during access cavity preparation,
      initial file placement and pulpectomy using visual analog scale (VAS). All data
      were analyzed and compared using the chi-square and Mann-Whitney tests. RESULTS:
      Except for one patient in the control group, all others had deep and long-lasting
      anesthesia. The difference between pain intensity of the control and experimental
      groups was not statistically significant (P>0.05). CONCLUSION: Addition of
      fentanyl to conventional local anesthetic solution did not increase the
      effectiveness of infiltration in patients diagnosed with IRP.

PMID- 25386213
TI  - Outcomes of different vital pulp therapy techniques on symptomatic permanent
      teeth: a case series.
AB  - In modern endodontics, vital pulp therapy (VPT) has been considered an ultra
      conservative treatment modality. Based on the level of pulp preservation, VPT
      includes stepwise excavation, indirect pulp capping (IDPC), direct pulp capping
      (DPC), miniature pulpotomy (MP), partial/Cvek pulpotomy and coronal/complete
      pulpotomy (CP). The present article reviews the treatment outcomes of 94
      permanent teeth with irreversible pulpitis treated with either IDPC (n=28), DPC
      (n=28), MP (n=29) or CP (n=9) using calcium-enriched mixture (CEM) cement. After
      a mean follow-up time of 12.3 months, 93 treated teeth were
      radiographic/clinically successful; only one radiographic failure was observed in
      the DPC group. 

PMID- 25386214
TI  - Root canal treatment of a two-rooted C-shaped maxillary first molar: a case
      report.
AB  - The most difficult maxillary teeth for endodontic treatment are the maxillary
      first molars (MFM) due to their complex root canal anatomy. The presence of two
      roots and C-shaped canals in MFMs has been reported in rare cases. The present
      case reports root canal treatment of MFM with two roots, where the palatal and
      buccal roots were joined together in a C-shaped configuration. 

PMID- 25386215
TI  - Endodontic treatment of a double-rooted maxillary second molar with four canals:
      a case report.
AB  - A healthy female was referred to Endodontic Department. The referral letter from
      her dentist expressed that an emergency pulpotomy of tooth #27 had been carried
      out with probable perforation of the chamber floor which was due to the unusual
      anatomy of the chamber. Cone-beam computed tomography (CBCT) revealed that the
      tooth had two mesial and two distal canals. Perforation site was repaired and
      endodontic treatment was completed. At 24-month follow-up, patient was
      asymptomatic and clinical and radiographic examinations showed successful
      outcomes. 

PMID- 25386216
TI  - Glycyrrhizae radix methanol extract attenuates methamphetamine-induced locomotor
      sensitization and conditioned place preference.
AB  - Glycyrrhizae Radix modulates the neurochemical and locomotor alterations induced
      by acute psychostimulants in rodents via GABAb receptors. This study investigated
      the influence of methanol extract from Glycyrrhizae Radix (MEGR) on repeated
      methamphetamine- (METH-) induced locomotor sensitization and conditioned place
      preference (CPP). A cohort of rats was treated with METH (1 mg/kg/day) for 6
      consecutive days, subjected to 6 days of withdrawal, and then challenged with the
      same dose of METH to induce locomotor sensitization; during the withdrawal
      period, the rats were administered MEGR (60 or 180 mg/kg/day). A separate cohort
      of rats was treated with either METH or saline every other day for 6 days in METH
      paired or saline-paired chambers, respectively, to induce CPP. These rats were
      also administered MEGR (180 mg/kg) prior to every METH or CPP expression test.
      Pretreatment with MEGR (60 and 180 mg/kg/day) attenuated the expression of METH
      induced locomotor sensitization dose-dependently, and 180 mg/kg MEGR
      significantly inhibited the development and expression of METH-induced CPP.
      Furthermore, administration of a selective GABAb receptor antagonist (SCH50911)
      prior to MEGR treatment effectively blocked the inhibitory effects of MEGR on
      locomotor sensitization, but not CPP. These results suggest that Glycyrrhizae
      Radix blocked repeated METH-induced behavioral changes via GABAb receptors. 

PMID- 25386218
TI  - Ultrasound-Guided Miniscalpel-Needle Release versus Dry Needling for Chronic Neck
      Pain: A Randomized Controlled Trial.
AB  - Objective. To compare ultrasound-guided miniscalpel-needle (UG-MSN) release
      versus ultrasound-guided dry needling (UG-DN) for chronic neck pain. Methods. A
      total of 169 patients with chronic neck pain were randomized to receive either UG
      MSN release or UG-DN. Before treatment and at 3 and 6 months posttreatment, pain
      was measured using a 10-point visual analogue scale (VAS). Neck function was
      examined using the neck disability index. Health-related quality of life was
      examined using the physical component score (PCS) and mental component score
      (MCS) of the SF-36 health status scale. Results. Patients in the UG-MSN release
      had greater improvement on the VAS (by 2 points at 3 months and 0.9 points at 6
      months) versus in the UG-DN arm; (both P < 0.0001). Patients receiving UG-MSN
      release also showed significantly lower scores on the adjusted neck disability
      index, as well as significantly lower PCS. No severe complications were observed.
      Conclusion. UG-MSN release was superior to UG-DN in reducing pain intensity and
      neck disability in patients with chronic neck pain and was not associated with
      severe complications. The procedural aspects in the two arms were identical;
      however, we did not verify the blinding success. As such, the results need to be
      interpreted with caution. 

PMID- 25386219
TI  - Compound danshen dripping pill pretreatment to prevent contrast-induced
      nephropathy in patients with acute coronary syndrome undergoing percutaneous
      coronary intervention.
AB  - Background. Contrast-induced nephropathy (CIN) limits the outcome of percutaneous
      coronary intervention (PCI). Objective. To investigate whether pretreatment with
      Compound Danshen Dripping Pills (CDDP) will decrease the incidence of CIN after
      PCI. Methods. A total of 229 patients with acute coronary syndrome (ACS)
      undergoing PCI were divided into the control group (n = 114) and the CDDP
      (containing salvia miltiorrhiza and sanqi) group (n = 115; given 20 CDDP pills,
      three times daily before PCI). Serum creatinine, creatinine clearance (CrCl),
      high-sensitivity C-reactive protein (hsCRP), P-selectin, and intercellular
      adhesion molecule-1 (ICAM-1) were measured at admission and 24 and 48 h after
      PCI. Results. CrCl decreased after PCI but recovered after 48 h. In the CDDP
      group, CrCl recovered more rapidly (P < 0.05). The procedure increased the hsCRP,
      P-selectin, and ICAM-1 levels, but these levels were less in the CDDP group (P <
      0.05). Conclusions. Pretreatment with CDDP can decrease the occurrence of CIN in
      patients undergoing PCI, suggesting that the early use of CDDP is an appropriate
      adjuvant pharmacological therapy before PCI. 

PMID- 25386217
TI  - Honey: a potential therapeutic agent for managing diabetic wounds.
AB  - Diabetic wounds are unlike typical wounds in that they are slower to heal, making
      treatment with conventional topical medications an uphill process. Among several
      different alternative therapies, honey is an effective choice because it provides
      comparatively rapid wound healing. Although honey has been used as an alternative
      medicine for wound healing since ancient times, the application of honey to
      diabetic wounds has only recently been revived. Because honey has some unique
      natural features as a wound healer, it works even more effectively on diabetic
      wounds than on normal wounds. In addition, honey is known as an "all in one"
      remedy for diabetic wound healing because it can combat many microorganisms that
      are involved in the wound process and because it possesses antioxidant activity
      and controls inflammation. In this review, the potential role of honey's
      antibacterial activity on diabetic wound-related microorganisms and honey's
      clinical effectiveness in treating diabetic wounds based on the most recent
      studies is described. Additionally, ways in which honey can be used as a safer,
      faster, and effective healing agent for diabetic wounds in comparison with other
      synthetic medications in terms of microbial resistance and treatment costs are
      also described to support its traditional claims. 

PMID- 25386220
TI  - Ergosterol Is the Active Compound of Cultured Mycelium Cordyceps sinensis on
      Antiliver Fibrosis.
AB  - Cultured mycelium Cordyceps sinensis (CMCS) is a Chinese herbal medicine, which
      is widely used for a variety of diseases including liver injury in clinic. The
      current study aims to investigate the protective effects of CMCS against liver
      fibrosis and to exploit its active antifibrotic substances in vivo and in vitro.
      For evaluating the antifibrotic effect of CMCS and ergosterol, male C57BL/6 mice
      were injected intraperitoneally with carbon tetrachloride (CCl4) and treated with
      CMCS (120 mg/kg/d) or ergosterol (50 mg/kg/d). Four weeks later, serum liver
      function, hepatic hydroxyproline (Hyp) content, liver inflammation, collagen
      deposition, and expression of alpha smooth muscle actin (alpha-SMA) in liver
      tissue were evaluated. Besides, toxicological effects of active compounds of CMCS
      on hepatocytes and hepatic stellate cells (HSCs) were detected and expressions of
      permeability of the lysosomal membrane, EdU, F-actin, and alpha-SMA of activated
      HSCs were analyzed to screen the antifibrotic substance in CMCS in vitro. Our
      results showed that CMCS could significantly alleviate levels of serum liver
      functions, attenuate hepatic inflammation, decrease collagen deposition, and
      relieve levels of alpha-SMA in liver, respectively. Ergosterol, the active
      compound in CMCS that was detected by HPLC, played a dose-dependent inhibition
      role on activated HSCs via upregulating expressions of permeability of the
      lysosomal membrane and downregulating levels of EdU, F-actin, and alpha-SMA on
      activated HSCs in vitro. Moreover, ergosterol revealed the antifibrotic effect
      alike in vivo. In conclusion, CMCS is effective in alleviating liver fibrosis
      induced by CCl4 and ergosterol might be the efficacious antifibrotic substance in
      CMCS in vivo and in vitro. 

PMID- 25386221
TI  - Reproductive responses of birds to experimental food supplementation: a meta
      analysis.
AB  - INTRODUCTION: Food availability is an important environmental cue for animals for
      deciding how much to invest in reproduction, and it ultimately affects population
      size. The importance of food limitation has been extensively studied in
      terrestrial vertebrate populations, especially in birds, by experimentally
      manipulating food supply. However, the factors explaining variation in
      reproductive decisions in response to food supplementation remain unclear. By
      performing meta-analyses, we aim to quantify the extent to which supplementary
      feeding affects several reproductive parameters in birds, and identify the key
      factors (life-history traits, behavioural factors, environmental factors, and
      experimental design) that can induce variation in laying date, clutch size and
      breeding success (i.e., number of fledglings produced) in response to food
      supplementation. RESULTS: Food supplementation produced variable but mostly
      positive effects across reproductive parameters in a total of 201 experiments
      from 82 independent studies. The outcomes of the food effect were modulated by
      environmental factors, e.g., laying dates advanced more towards low latitudes,
      and food supplementation appeared not to produce any obvious effect on bird
      reproduction when the background level of food abundance in the environment was
      high. Moreover, the increase in clutch size following food addition was more
      pronounced in birds that cache food, as compared to birds that do not.
      Supplementation timing was identified as a major cause of variation in breeding
      success responses. We also document the absence of a detectable food effect on
      clutch size and breeding success when the target species had poor access to the
      feed due to competitive interactions with other animals. CONCLUSIONS: Our
      findings indicate that, from the pool of bird species and environments reviewed,
      extra food is allocated to immediate reproduction in most cases. Our results also
      support the view that bird species have evolved different life-history strategies
      to cope with environmental variability in food supply. However, we encourage more
      research at low latitudes to gain knowledge on how resource allocation in birds
      changes along a latitudinal gradient. Our results also emphasize the importance
      of developing experimental designs that minimise competition for the supplemented
      food and the risk of reproductive bottle-necks due to inappropriate
      supplementation timings.

PMID- 25386222
TI  - Shear stress-induced NO production is dependent on ATP autocrine signaling and
      capacitative calcium entry.
AB  - Flow-induced production of nitric oxide (NO) by endothelial cells plays a
      fundamental role in vascular homeostasis. However, the mechanisms by which shear
      stress activates NO production remain unclear due in part to limitations in
      measuring NO, especially under flow conditions. Shear stress elicits the release
      of ATP, but the relative contribution of autocrine stimulation by ATP to flow
      induced NO production has not been established. Furthermore, the importance of
      calcium in shear stress-induced NO production remains controversial, and in
      particular the role of capacitive calcium entry (CCE) has yet to be determined.
      We have utilized our unique NO measurement device to investigate the role of ATP
      autocrine signaling and CCE in shear stress-induced NO production. We found that
      endogenously released ATP and downstream activation of purinergic receptors and
      CCE plays a significant role in shear stress-induced NO production. ATP-induced
      eNOS phophorylation under static conditions is also dependent on CCE. Inhibition
      of protein kinase C significantly inhibited eNOS phosphorylation and the calcium
      response. To our knowledge, we are the first to report on the role of CCE in the
      mechanism of acute shear stress-induced NO response. In addition, our work
      highlights the importance of ATP autocrine signaling in shear stress-induced NO
      production.

PMID- 25386223
TI  - Measurement of ATP-Induced Membrane Potential Changes in IVD cells.
AB  - Extracellular adenosine-5'-triphosphate (ATP) triggers biological responses in a
      wide variety of cells and tissues and activates signaling cascades that affect
      cell membrane potential and excitability. It has been demonstrated that
      compressive loading promotes ATP production and release by intervertebral disc
      (IVD) cells, while a high level of extracellular ATP accumulates in the nucleus
      pulposus (NP) of the IVD. In this study, a noninvasive system was developed to
      measure ATP-induced changes in the membrane potential of porcine IVD cells using
      the potential sensitive dye di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl
      sulfonate (di-8-ANEPPS).The responses of NP and annulus fibrosus (AF) cells to
      ATP were examined in monolayer and 3-dimensional cultures. It was found that the
      pattern and magnitude of membrane potential change in IVD cells induced by
      extracellular ATP depended on cell type, culture condition, and ATP dose. In
      addition, gene expression of P2X4 purinergic receptor was found in both cell
      types. Inhibition of the ATP-induced response by pyridoxalphosphate-6-azophenyl
      2', 4'-disulfonate (PPADS), a non-competitive inhibitor of P2 receptors, suggests
      that ATP may modulate the biological activities of IVD cells via P2 purinergic
      receptors.

PMID- 25386224
TI  - Patients' Perspectives on Integrating Acupuncture into the Radiation Oncology
      Setting.
AB  - INTRODUCTION: Acupuncture has potential as a supportive care service for cancer
      symptom management. However, little is known about patients' willingness to use
      acupuncture in the context of conventional cancer care. METHODOLOGY: We conducted
      a cross-sectional survey study among patients with cancer during their last week
      of fractionated/external beam radiotherapy (RT). The main outcome variable was
      self-reported likelihood of using acupuncture during RT. Knowledge about
      acupuncture and pain severity was measured along with socio-demographic and
      clinical variables. Multivariate logistic regression was performed to identify
      factors associated with willingness to use acupuncture. RESULTS: Among the 305
      participants, 79 (26.4%) were likely to use acupuncture during RT if such
      services were offered at a reasonable price, 143 (46.9%) had no knowledge of
      acupuncture, and 206 (67.6%) reported having pain. In multivariate analyses, non
      Whites (adjusted odds ratio [AOR] 1.94, 95% Confidence Interval [CI] 1.06-3.56),
      and those with pain (AOR 2.52, CI 1.25-5.10) were more interested in using
      acupuncture. In addition, patients with preexisting knowledge about acupuncture
      were also more likely to use acupuncture than those without this knowledge (AOR
      2.23, CI 1.28-3.88). CONCLUSIONS: Patients of non-White race, those with pain or
      those with prior knowledge about acupuncture were more willing to utilize
      acupuncture during RT. Since half of the patients had no knowledge about
      acupuncture, interventions to improve patients' knowledge are needed to
      facilitate the successful integration of acupuncture into cancer care.

PMID- 25386225
TI  - The role of elastosonography in the differentiation of parotid gland lesions:
      report of three cases and review of the literature.
AB  - BACKGROUND: The parotid gland is the mostly affected site among major salivary
      gland tumors in up to 85% of cases. Preoperative knowledge of the tumour nature
      is crucial since it influences the surgical procedure and patient's morbidity,
      especially the risk of facial nerve palsy. Ultrasonography is commonly used as
      the first line imaging modality for the salivary gland lesions. A pitfall is that
      the histologic pleomorphism often reflects an imaging pleomorphism. CASE REPORT:
      HEREIN WE AIMED TO PRESENT THE ROLE OF ELASTOSONOGRAPHY IN THREE PAROTID LESIONS:
      a case of benign pleomorphic adenoma, a Wharthin's tumour and a malignant parotid
      tumour. CONCLUSIONS: Our findings show that malignant parotid lesion was the
      stiffest lesion according to elastosonography. Wharthin's tumour demonstrated
      soft elastosonographic features. The pleomorphic adenoma was also interpreted as
      stiff by elastosonography suggesting that the elastosonographic features of
      pleomorphic adenoma may resemble those of malignant lesions limiting the utility
      of the technique.

PMID- 25386226
TI  - Astragalus polysaccharide suppresses doxorubicin-induced cardiotoxicity by
      regulating the PI3k/Akt and p38MAPK pathways.
AB  - BACKGROUND: Doxorubicin, a potent chemotherapeutic agent, is associated with
      acute and chronic cardiotoxicity, which is cumulatively dose-dependent.
      Astragalus polysaccharide (APS), the extract of Astragalus membranaceus with
      strong antitumor and antiglomerulonephritis activity, can effectively alleviate
      inflammation. However, whether APS could ameliorate chemotherapy-induced
      cardiotoxicity is not understood. Here, we investigated the protective effects of
      APS on doxorubicin-induced cardiotoxicity and elucidated the underlying
      mechanisms of the protective effects of APS. METHODS: We analyzed myocardial
      injury in cancer patients who underwent doxorubicin chemotherapy and generated a
      doxorubicin-induced neonatal rat cardiomyocyte injury model and a mouse heart
      failure model. Echocardiography, reactive oxygen species (ROS) production, TUNEL,
      DNA laddering, and Western blotting were performed to observe cell survival,
      oxidative stress, and inflammatory signal pathways in cardiomyocytes. RESULTS:
      Treatment of patients with the chemotherapeutic drug doxorubicin led to heart
      dysfunction. Doxorubicin reduced cardiomyocyte viability and induced C57BL/6J
      mouse heart failure with concurrent elevated ROS generation and apoptosis, which,
      however, was attenuated by APS treatment. In addition, there was profound
      inhibition of p38MAPK and activation of Akt after APS treatment. CONCLUSIONS:
      These results demonstrate that APS could suppress oxidative stress and apoptosis,
      ameliorating doxorubicin-mediated cardiotoxicity by regulating the PI3k/Akt and
      p38MAPK pathways.

PMID- 25386227
TI  - Oxidative status imbalance in patients with metabolic syndrome: role of the
      myeloperoxidase/hydrogen peroxide axis.
AB  - The present study evaluated the cardiometabolic and redox balance profiles in
      patients with Metabolic Syndrome compared to apparently healthy individuals, and
      the participation of the myeloperoxidase/hydrogen peroxide axis in systemic lipid
      peroxidation. Twenty-four patients with Metabolic Syndrome and eighteen controls
      underwent a full clinical assessment. Venous blood samples were collected for
      general biochemical dosages, as well as for the oxidative stress analyses
      (superoxide dismutase, catalase, and arginase activities; and lipid peroxidation,
      myeloperoxidase activity, nitrite, and hydrogen peroxide concentrations in
      plasma). Arterial stiffness was assessed by radial artery applanation tonometry.
      Plasma lipid peroxidation, erythrocyte superoxide dismutase activity,
      myeloperoxidase activity, and hydrogen peroxide concentrations were shown to be
      increased in Metabolic Syndrome patients, without significant differences for the
      other enzymes, plasma nitrite concentrations, and arterial stiffness. Linear
      regression analysis revealed a positive and significant correlation between lipid
      peroxidation and myeloperoxidase and also between this enzyme and hydrogen
      peroxide. In contrast, such correlation was not observed between lipid
      peroxidation and hydrogen peroxide. In summary, Metabolic Syndrome patients
      exhibited evident systemic redox imbalance compared to controls, with the
      possible participation of the myeloperoxidase/hydrogen peroxide axis as a
      contributor in lipid peroxidation.

PMID- 25386228
TI  - Titanium surfaces with nanostructures influence on osteoblasts proliferation: a
      systematic review.
AB  - OBJECTIVES: Nanothechnology found to be increasingly implemented in implantology
      sphere over the recent years and it shows encouraging effect in this field. The
      aim of present review is to compare, based on the recent evidence, the influence
      of various nanostructure surface modifications of titanium for implants, on
      osteoblasts proliferation. MATERIAL AND METHODS: A literature review of English
      articles was conducted by using MEDLINE database restricted to 2009 - 2014 and
      constructed according PRISMA guidelines. Search terms included "Titanium
      implant", "Titanium surface with nanostructure", "Osteoblast". Additional studies
      were identified in bibliographies. Only in vitro and/or in vivo studies on nano
      structured implant surfaces plus control sample, with specific evaluation method
      for osteoblasts proliferation and at least one Ti sample with nanostructure, were
      included in the review. RESULTS: 32 studies with 122 groups of examined samples
      were selected for present review. Each study conducted in vitro experiment, two
      studies conducted additional in vivo experiments. All studies were dispensed by
      type of surface modification into two major groups; "Direct ablative titanium
      implant surface nano-modifications" with 19 studies and "Nanocomposite additive
      implant surface modifications" with 13 studies. Overall 24 studies reporting on
      positive effect of nanostructured surface, 2 studies found no significant
      advantage and 6 studies reported on negative effect compared to other structure
      scales. CONCLUSIONS: From examination of selected articles we can notice marked
      advantage in implementation of various nanostructures onto implant surface. Yet
      for discovering the ultimate implant surface nanostructure, further comparable
      investigations of Ti surface nanostructures need to be done.

PMID- 25386229
TI  - Self-Reported Facial Pain in UK Biobank Study: Prevalence and Associated Factors.
AB  - OBJECTIVES: To determine the prevalence of facial pain and to examine the
      hypothesis that symptoms are associated with socio-demographic, dental, adverse
      psychological factors and pain elsewhere in the body. MATERIAL AND METHODS: Cross
      sectional population data were obtained from UK Biobank (www.ukbiobank.ac.uk/)
      study which was conducted in 2006 - 2010 and recruited over 500,000 people.
      RESULTS: The overall prevalence of facial pain (FP) was 1.9% (women 2.4%, men
      1.2%) of which 48% was chronic. The highest prevalence was found in the 51 - 55
      age group (2.2%) and the lowest in the 66 - 73 age group (1.4%). There was a
      difference in prevalence by ethnicity (0.8% and 2.7% in persons reporting
      themselves as Chinese and Mixed respectively). Prevalence of FP significantly
      associated with all measures of social class with the most deprived and on lowest
      income showing the highest prevalence (2.5% and 2.4% respectively). FP was more
      common in individuals who rated themselves as extremely unhappy, had history of
      depression and reported sleep problems. Smoking associated with increase in
      reporting FP while alcohol consumption had inverse association. FP associated
      with history of painful gums, toothache and all types of regional pain.
      CONCLUSIONS: This is the largest ever study to provide estimates of facial pain
      prevalence. It demonstrates unique features (lower prevalence than previously
      reported) and common features (more common in women) and confirms multifactorial
      aetiology of facial pain. Significant association with psychological distress and
      a strong relationship to pain elsewhere in the body suggests that aetiology is
      not specific to this regional pain.

PMID- 25386230
TI  - The influence of 1alpha.25-dihydroxyvitamin d3 coating on implant
      osseointegration in the rabbit tibia.
AB  - OBJECTIVES: This study aims to evaluate bone response to an implant surface
      modified by 1alpha,25-dihydroxyvitamin D3 [1.25-(OH)2D3] in vivo and the
      potential link between 1.25-(OH) 2D3 surface concentration and bone response.
      MATERIAL AND METHODS: Twenty-eight implants were divided into 4 groups (1
      uncoated control, 3 groups coated with 1.25-(OH)2D3 in concentrations of 10(-8),
      10(-7) and 10(-6) M respectively), placed in the rabbit tibia for 6 weeks.
      Topographical analyses were carried out on coated and uncoated discs using
      interferometer and atomic-force-microscope (AFM). Twenty-eight implants were
      histologically observed (bone-to-implant-contact [BIC] and new-bone-area [NBA]).
      RESULTS: The results showed that the 1.25-(OH)2D3 coated implants presented a
      tendency to osseointegrate better than the non-coated surfaces, the differences
      were not significant (P > 0.05). CONCLUSIONS: The effect of 1.25-(OH)2D3 coating
      to implants suggested possible dose dependent effects, however no statistical
      differences could be found. It is thought that the base substrate topography
      (turned) could not sustain sufficient amount of 1.25-(OH)2D3 enough to present
      significant biologic responses. Thus, development a base substrate that can
      sustain 1.25-(OH)2D3 for a long period is necessary in future studies.

PMID- 25386231
TI  - Stability of the anterior maxillary segment and teeth after segmental le fort I
      osteotomy and postoperative skeletal elastic fixation with or without occlusal
      splint.
AB  - OBJECTIVES: To assess the short term dental and skeletal stability of the
      anterior maxillary segment after segmental Le Fort I osteotomy with postoperative
      skeletal elastic fixation with or without occlusal splint. MATERIAL AND METHODS:
      29 consecutive patients underwent segmental Le Fort I osteotomy and elastic
      skeletal fixation was applied. Patients were divided into two groups according to
      whether a fixed occlusal splint was used for six weeks (group A) or dismounted
      perioperatively (group B). Changes in landmarks and reference planes between the
      two timepoints were estimated on lateral cephalometric radiographs. RESULTS: 
      GROUP A: The upper incisor had a mean intrusion of -0.56 mm (SD 0.77; range -2.04
      to 1.08 mm) and a mean posterior movement of -0.93 mm (SD 1.03; range -2.52 to
      0.96 mm). The mean change in the axial inclination of the upper incisor was -0.33
      degrees  (SD 2.56; range -6 degrees  to 4 degrees ) (95% CI: -1.75 to 1.08
      degrees ). Group B: The upper incisor had a mean intrusion of -0.13 mm (SD 1.36;
      range -1.92 to 3.6 mm) and a mean anterior movement of 0.11 mm (SD 1.78; range 
      2.88 to 3.84 mm). The mean change in the axial inclination of the upper incisor
      was -0.07 degrees  (SD 3.05; range -5 degrees  to 5 degrees ) (95% CI: -1.83 to
      1.69 degrees ). There was no statistically significant difference in stability
      between the two groups at the P value 0.05. CONCLUSIONS: The skeletal anterior
      fixation with postoperative elastics for eight weeks may not compromise the early
      postoperative dental and skeletal stability of the anterior segment in segmental
      Le Fort I osteotomy.

PMID- 25386232
TI  - Accidental displacement of third molar into the sublingual space: a case report.
AB  - BACKGROUND: Successful extraction of third molars depends on preoperative
      diagnosis and planning. Gold standard preoperative examinations are performed
      through computed tomography, decreasing risks and avoiding potential accidents.
      The present report highlights the value of preoperative examinations in face of
      accidentally displaced third molars. METHODS: An 18-years-old female patient
      underwent a third mandibular molar extraction with a general dentist.
      Accidentally, the mandibular left third molar was displaced into the sublingual
      space, making necessary a second surgical step. The surgery was interrupted and
      the patient was referred to an expert in maxillofacial surgery. RESULTS: After 21
      days awaiting an asymptomatic health status, the second surgical step was
      successfully performed using multislice computed tomography as preoperative
      imaging guide. CONCLUSIONS: The present case report highlights the clinical
      usefulness of imaging planning and informed consents in face of legal and ethic
      potential complaints.

PMID- 25386233
TI  - Tight junctions in Hailey-Hailey and Darier's diseases.
AB  - Hailey-Hailey disease (HHD) and Darier's disease (DD) are caused by mutations in
      Ca(2+)-ATPases with the end result of desmosomal disruption and suprabasal
      acantholysis. Tight junctions (TJ) are located in the granular cell layer in
      normal skin and contribute to the epidermal barrier. Aberrations in the epidermal
      differentiation, such as in psoriasis, have been shown to lead to changes in the
      expression of TJ components. Our aim was to elucidate the expression and dynamics
      of the TJ proteins during the disruption of desmosomes in HHD and DD lesions.
      Indirect immunofluorescence and avidin-biotin labeling for TJ, desmosomal and
      adherens junction proteins, and subsequent analyses with the confocal laser
      scanning microscope were carried out on 14 HHD and 14 DD skin samples.
      Transepidermal water loss (TEWL) was measured in normal and lesional epidermis of
      nine HHD and eight DD patients to evaluate the function of the epidermal barrier
      in HHD and DD skin. The localization of TJ proteins claudin-1, claudin-4, ZO-1,
      and occludin in perilesional HHD and DD epidermis was similar to that previously
      described in normal skin. In HHD lesions the tissue distribution of ZO-1 expanded
      to the acantholytic spinous cells. In agreement with previous findings,
      desmoplakin was localized intracellularly. In contrast claudin-1 and ZO-1
      persisted in the cell-cell contact sites of acantholytic cells. TEWL was
      increased in the lesional skin. The current results suggest that TJ components
      follow different dynamics in acantholysis of HHD and DD compared to desmosomal
      and adherens junction proteins. 

PMID- 25386234
TI  - Increase of integrin alpha6+p63+ cells after ultraviolet B irradiation in normal
      human keratinocytes.
AB  - Epidermal stem cells (SC) are believed to be resistant to environmental damage
      for the purpose of self renewal. Most promising SC markers include integrin
      alpha6 and p63. The aim of our study was to determine whether the integrin
      alpha6+p63+ cell fraction representative of the epidermal progenitor or SC is
      increased after ultraviolet B (UVB) irradiation and to clarify the hypothesis
      that epidermal SC are resistant to high-dose UVB damage. We irradiated early
      passage normal human keratinocytes (NHK) with 0, 25, 50, and 100 mJ/cm(2) UVB.
      The percentage of cell death was calculated. Real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) and western blotting analyses were performed
      to identify integrin alpha6 and p63, and flow cytometry analysis with integrin
      alpha6 and p63 antibodies was done. After 50 and 100 mJ/cm(2) UVB, integrin
      alpha6+p63+ cells were found to be much increased by fluorescence-activated cell
      sorting. Expression of integrin alpha6 and p63 was increased in NHK after UVB
      irradiation, which was shown with real-time RT-PCR and western blotting analyses.
      We concluded that an increase of integrin alpha6+p63+ cells after high-dose UVB
      may suggest that the putative progenitor or SC are resistant to UVB irradiation. 

PMID- 25386235
TI  - Seasonal onychomadesis in an elderly gentleman.
AB  - A 79-year-old man with a history of dementia and hypertension initially presented
      with a ten year history of Beau's lines and seasonal nail shedding of his
      fingernails only. He denied any exposure to heavy metals, unusual activities or
      food. He stated that the seasonal nail shedding had been occurring for the last 5
      10 years. On examination, six out of ten fingernails had been affected. He had
      significant toenail dystrophy. Fungal cultures and PAS staining of the toenails
      were negative. Routine serum biochemistry and haematology results were normal.
      Serum arsenic, cadmium and lead levels were also normal. Vitamin B12, zinc,
      folate, iron studies, thyroid function studies and homocysteine levels were also
      normal. Rheumatoid factor and anti-cyclic citrullinated peptide antibody
      antibodies were negative. Bilateral hand X-ray showed osteoarthritic change and
      did not show any features of psoriatic arthropathy. We discuss the case of a 79
      year-old man with seasonal nail shedding, curiously affecting his fingernails
      only. 

PMID- 25386236
TI  - A case of rheumatic fever with acute post-streptococcal glomerulonephritis and
      nephrotic syndrome caused by a cutaneous infection with beta-hemolytic
      streptococci.

PMID- 25386237
TI  - Keratoacanthoma centrifugum marginatum: unresponsive to oral retinoid and
      successfully treated with wide local excision.
AB  - We describe a case of a 65-year-old male presenting with a large plaque with a
      rolled-out interrupted margin, atrophic center, and island of normal skin over
      the left arm. It grew peripherally with central healing, and there was a history
      of recurrence after inadequate excision. Investigations ruled out other clinical
      mimickers; namely, squamous cell carcinoma, lupus vulgaris, botryomycosis, and
      blastomycosis-like pyoderma. Histopathological sections showed irregularly shaped
      craters filled with keratin and epithelial pearl but no evidence of granuloma or
      cellular atypia. Clinicopathological correlation proved the lesion to be
      keratoacanthoma centrifugum marginatum (KCM), a rare variant of keratoacanthoma,
      which spreads centrifugally, attains a huge size, and never involutes
      spontaneously. Treatment of KCM has been a problem always and, in our case,
      systemic retinoid (acitretin for three months) proved ineffective. The patient
      also had a history of recurrence following surgical intervention previously,
      necessitating wide excision to achieve complete clearance of tumor cells. Hence,
      after failure of retinoid therapy, the decision of excision with a 1-centimeter
      margin was taken and the large defect was closed by a split thickness skin graft.
      The graft uptake was satisfactory, and the patient is being followed-up presently
      and shows no signs of recurrence after six months, highlighting wide local
      excision as a useful treatment option. 

PMID- 25386238
TI  - Cutaneous papules in a patient with acquired immunodeficiency syndrome.
AB  - During the past decade or so, the incidence of syphilis has increased in most
      parts of the world. In some urban regions, a coinfection with human
      immunodeficiency virus is disclosed in nearly 50% of the cases. Owing to the
      polymorphism of the lesions, the clinical diagnosis may be puzzling. The homing
      patterns and migration paths of Treponema pallidum in the skin during early
      syphilis represent the preliminary steps preceding dissemination to other organs.
      Immunohistochemistry directed to T. pallidum is a convenient means for reaching
      the diagnosis and for exploring the dissemination process. The present case
      illustrates the dermal clustering and the vascular spread of T. pallidum in a
      woman with acquired immunodeficiency syndrome. 

PMID- 25386239
TI  - Proteus syndrome: a case report and a case study review in China.
AB  - Proteus syndrome (PS) is a rare and sporadic disorder characterized by overgrowth
      of multiple tissues and a propensity to develop particular neoplasms. The
      clinical manifestations of PS include macrodactyly, vertebral abnormalities,
      asymmetric limb overgrowth and length discrepancy, hyperostosis, abnormal and
      asymmetric fat distribution, asymmetric muscle development, connective tissue
      nevi, and vascular malformations. We report a 16-year old female patient who
      manifested a number of these complications and review the Chinese literature
      about the diagnosis, natural history, and management of PS. 

PMID- 25386240
TI  - Acitretin systemic and retinoic acid 0.1% cream supression of basal cell
      carcinoma.
AB  - Retinoids have been used for years as monotherapy and/or in combination for
      treatment and suppression of cutaneous malignancies in patients with basal cell
      nevus syndrome, xeroderma pigmentosum, or cutaneous T-cell lymphoma (CTCL) basal
      cell carcinoma (BCC). We report 4 cases with BCC confirmed by histopathology who
      were treated by short-term systemic acitretin combined with retinoic acid 0.1%
      cream. The 4 cases with BCC showed good response to the treatment without severe
      adverse effects during treatment and follow-up. The finding suggests that
      acitretin may be an appropriate treatment option for elderly patients who require
      less invasive treatment for BCC. 

PMID- 25386241
TI  - Neutrophilic dermatoses in a patient with collagenous colitis.
AB  - We report the case of a 75-year old woman with collagenous colitis who presented
      with erythematous and edematous plaques on the periorbital and eyelid regions,
      accompanied by oral ulcers. Histopathology showed a dermal neutrophilic
      infiltrate plus mild septal and lobular panniculitis with lymphocytes,
      neutrophils and eosinophils. Five years earlier she had presented a flare of
      papules and vesicles on the trunk, together with oral ulcers; a skin biopsy
      revealed a neutrophilic dermal infiltrate and Sweet's syndrome was diagnosed.
      Both the neutrophilic panniculitis and the Sweet's syndrome were accompanied by
      fever, malaise and diarrhea. Cutaneous and intestinal symptoms disappeared with
      corticoid therapy. The two types of neutrophilic dermatoses that appeared in
      periods of colitis activity suggest that intestinal and cutaneous manifestations
      may be related. 

PMID- 25386242
TI  - Stevens-Johnson syndrome/erythema multiforme major and Chlamydia pneumoniae
      infection in young patients.
AB  - Erythema multiforme major (EMM) is an acute, self-limited mucocutaneous disease
      characterized by the abrupt onset of symmetrical fixed red papules evolving to
      target lesions. It is triggered mainly by infections, such as herpes simplex
      virus (HSV) and Mycoplasma pneumoniae, or drugs. In instances of extensive skin
      lesions with "giant" targets, prominent involvement of several mucous sites and
      fever, it may be difficult to distinguish from Stevens-Johnson syndrome (SJS), a
      rarer, life-threatening reaction which is mainly drug-induced. We report a 7-year
      old boy with SJS and Chlamydia pneumoniae infection and 3 patients with erythema
      multiforme (EM) and co-infection with Chlamydia pneumoniae: a 3-year old girl and
      a 29-year old man developed EMM lesions associated to Mycoplasma pneumoniae and
      Chlamydia pneumonia and a 20-year old woman with EMM associated to herpes simplex
      type 2 and Chlamydia pneumoniae infection. None of the 4 patients had history of
      drug intake in the last two months. Chlamydia pneumoniae is an intracellular
      bacteria responsible for respiratory infections. Despite the fact that its role
      in SJS/EMM has been rarely reported, our cases suggest that it may cause SJS and
      trigger EM when co-infecting a patient, either with Mycoplasma pneumoniae or
      herpes simplex. We conclude that infection by Chlamydia pneumoniae should be
      suspected and ruled out in every patient with SJS/EMM, especially in those with
      signs of respiratory infection. 

PMID- 25386243
TI  - Quality of life in Swedish children with congenital ichthyosis.
AB  - Congenital ichthyosis encompasses a large group of keratinizing disorders with
      widespread scaling and a variable degree of erythema. Little is known about the
      quality of life in children with congenital ichthyosis and the impact of the
      disease on their family. Fifteen children aged 5-16 years with lamellar
      ichthyosis, Netherton's syndrome, epidermolytic hyperkeratosis or Harlequin
      ichthyosis, were investigated concerning the effect of their ichthyosis on their
      quality of life. This was measured with the established Children's Dermatology
      Life Quality Index (CDLQI), and the Dermatitis Family Impact questionnaire (DFI)
      modified by substituting the word ichthyosis for eczema. The questionnaires
      covered the preceding seven days and each had a maximum score of 30: the higher
      the score, the greater the Quality of Life impairment. The median score was 9.0
      (range 2-19) for the CDLQI and 9.0 (range 3-21) for DFI. There was a significant
      correlation between the DFI and the CDLQI scores. The item in the CDLQI
      questionnaire that showed the highest score was "itchy, scratchy, sore or painful
      skin" and the most highly scored item in the DFI questionnaire was effect on
      "housework, e.g. washing, cleaning"; both items related to the children's
      symptoms. The results of the study clearly establish that congenital ichthyosis
      impairs the quality of life of the affected children and their families. 

PMID- 25386244
TI  - Growth dynamics and cyclin expression in cutaneous T-cell lymphoma cell lines.
AB  - We have investigated cell growth dynamics and cyclins B1 and E expression in cell
      lines derived from mycosis fungoides (MyLa), Sezary syndrome (SeAx), and CD30(+)
      lympho-proliferative diseases (Mac1, Mac2a, JK). Mac1 and Mac2a had the highest
      growth rate (doubling time 18-28 h, >90% cycling cells) whereas SeAx was
      proliferating slowly (doubling time 55 h, approximately 35% cycling cells).
      Expression of cyclin B1 correlated positively with doubling time whereas
      expression of cyclin E was unscheduled and constant across the investigated cell
      lines. All cell lines exhibited high expression of PCNA. Thus, we concluded that
      cyclin B1 could be used for rapid screening of cell proliferation in malignant
      lymphocytes derived from cutaneous T-cell lymphoma. 

PMID- 25386245
TI  - Taxane-induced morphea in a patient with CREST syndrome.
AB  - The taxanes, docetaxel and paclitaxel, are microtubule stabilizing
      chemotherapeutic agents that have demonstrated antineoplastic effects in a
      variety of solid tumors. They have been linked to the development of localized
      cutaneous sclerosis in some patients. We present a case of docetaxel-induced
      cutaneous sclerosis of the lower extremities in a patient with pre-existing CREST
      syndrome. We propose that patients with a history of limited or diffuse systemic
      sclerosis should be given taxane chemotherapy with caution, as these patients may
      have an immunological predisposition for the development of drug-induced morphea.

PMID- 25386246
TI  - Elastosis Perforans Serpiginosa in a patient with Down syndrome treated with
      imiquimod 5% cream.
AB  - Elastosis Perforans Serpiginosa (EPS) is a rare skin disease characterised by
      hyperkeratotic papules, transepidermal elimination of abnormal elastic fibres,
      and focal dermal elastosis. The aetiology is unknown, but an association with
      underlying systemic disorders, including Down syndrome has been described.
      Treatment is often difficult. A 45-year old man with Down syndrome presented with
      symmetrical annular elements on forearms and femora. The elements were
      erythematous with atrophic hypopigmented central healing and peripherally,
      infiltrated keratotic papules with desquamation. A punch biopsy showed the
      classical histopathologic features of EPS. We found no clinical signs of
      cerebrovascular or cardiovascular disease. We initiated topical therapy with
      imiquimod 5% cream once a day for 6 weeks followed by 3 times weekly for 4 weeks
      to a single element. As regression of EPS was observed and the patient tolerated
      the therapy well, treatment of other lesions was commenced, and further
      regression was seen. 

PMID- 25386247
TI  - Actinic lichen nitidus.
AB  - We present the case of a 29-year-old black female with an initial clinical and
      histopathologic diagnosis of actinic lichen nitidus. Three years later, she
      presented with scattered hyperpigmented macules with oval pink/violaceous plaques
      bilaterally on her forearms and on her neck, clinically consistent with actinic
      lichen planus. She was treated with topical steroids at each visit, with
      subsequent resolution of her lesions. In this report, we discuss the spectrum of
      actinic lichenoid dermatoses and of disease that presents even in the same
      patient. 

PMID- 25386248
TI  - Side-effects to the use of laptop computers: erythema ab igne.
AB  - The use of laptop computers is increasing, and many children and young adults
      spend hours with their laptops on their laps daily. We report a case with
      erythema ab igne on the thigh of a 17-year-old girl, induced by use of laptop
      computers four to five hours daily for nine months. 

PMID- 25386249
TI  - 2-Chlorodeoxyadenosine treatment for cutaneous T-cell lymphoma.
AB  - The primary cutaneous lymphomas are often indolent but difficult to treat. In the
      early stages psoralen and ultraviolet-A therapy is the standard treatment whereas
      at the tumor stage chemotherapy (e.g. pegylated doxorubicin) is often used for
      debulking. The purine analog 2-chlorodeoxyadenosine (2CdA) acts in non-Hodgkin's
      lymphoma and has been used in our center for the treatment of advanced primary
      cutaneous T-cell lyphomas (CTCL). Here, we report on the efficacy and side
      effects of 2CdA in six patients with CTCL. One patient died owing to
      myelosuppression. Partial responses were seen in four cases but full remission
      was observed in only one case. We concluded that 2CdA has a limited usefulness in
      the management of advanced CTCL. 

PMID- 25386250
TI  - Photocarcinogenicity of selected topically applied dermatological drugs:
      calcineurin inhibitors, corticosteroids, and vitamin D analogs.
AB  - Topical therapies constitute the mainstay of dermatological treatments for skin
      disorders, such as atopic dermatitis, contact dermatitis, psoriasis, or acne.
      Since some of these diseases are often chronic, treatment duration may last for
      years and may even last the patient's entire lifetime. Obviously, such long-term
      therapy may raise safety concerns, which also include the potential
      photocarcinogenic effect. Most patients are exposed to ultraviolet radiation
      (UVR) during leisure, work, vacations, or in tanning beds. Additionally, the
      patients may receive UVR via UVB phototherapy or psoralens plus UVA radiation
      (PUVA). The use of immunosuppressant's, such as corticosteroids and calcineurin
      inhibitors, has markedly increased. Patients with skin diseases have benefited
      from both systemic and topical treatment of both new and established drugs. The
      issue of a black box warning by the US Food and Drug Administration has increased
      concerns about photocarcinogenesis, which raises the question: "Are these drugs
      safe?" This review focuses on the mechanism of action and photocarcinogenic
      potential of commonly used topical treatments, such as corticosteroids,
      calcineurin inhibitors, and vitamin D analogs. 

PMID- 25386251
TI  - A Characterization of the expression of 14-3-3 isoforms in psoriasis, basal cell
      carcinoma, atopic dermatitis and contact dermatitis.
AB  - 14-3-3 is a highly conserved protein involved in a number of cellular processes
      including cell signalling, cell cycle regulation and gene transcription. Seven
      isoforms of the protein have been identified; beta, gamma, epsilon, zeta eta
      sigma and tau. The expression profile of the various isoforms in skin diseases is
      unknown. To investigate the expression of the seven 14-3-3 isoforms in involved
      and uninvolved skin from psoriasis, basal cell carcinoma (BCC), atopic dermatitis
      and nickel induced allergic contact dermatitis. Punch biopsies from involved and
      uninvolved skin were analyzed with quantitative reverse transcription-polymerase
      chain reaction to determine the mRNA expression of the 14-3-3 isoforms. The
      protein level of 14-3-3 isoforms was measured by Western blot technique in
      keratome biopsies from patients with psoriasis. Evaluation of dermal and
      epidermal protein expression was performed by immunofluorescence staining.
      Increased 14-3-3tau mRNA levels were detected in involved skin from patients with
      psoriasis, contact dermatitis and BCC. 14-3-3sigma mRNA expression was increased
      in psoriasis and contact dermatitis, but not in BCC. In atopic dermatitis no
      significant difference between involved and uninvolved skin was found. The
      expression of the 14-3-3 isoforms was also studied at the protein level in
      psoriasis. Only 14-3-3tau expression was significantly increased in involved
      psoriatic skin compared with uninvolved skin. Immunofluorescence staining with 14
      3-3tau- and 14-3-3sigma-specific antibodies showed localization of both isoforms
      to the cytoplasm of the keratinocytes in the various skin sections. These results
      demonstrate a disease specific expression profile of the 14-3-3tau and 14-3
      3sigma iso-forms. 

PMID- 25386252
TI  - The interaction of inflammatory cells in granuloma faciale.
AB  - Granuloma faciale (GF) is a rare chronic inflammatory skin disease characterized
      by single or multiple reddish-brown cutaneous plaques or nodules. Although this
      condition is benign, its clinical course is extremely chronic with poor response
      to therapy. The typical histopathological features of GF include vasculitis with
      mixed cellular infiltration; however, its etiopathogenesis remains unknown. Here,
      we describe the case of a 76-year-old man with GF resistant to topical steroids.
      Biopsy of the lesion revealed i) dense mixed inflammatory cellular infiltrates of
      lymphocytes, histiocytes, neutrophils, and eosinophils, ii) mild perivascular
      nuclear dust and swollen endothelium of blood vessels, and iii) a narrow Grenz
      zone beneath the epidermis. Immunohistochemical staining demonstrated mixed
      cellular infiltrates intermixed with CD1a(+) dendritic cells, CD68(+)
      histiocytes, and CD4(+) and CD8(+) T cells. 

PMID- 25386253
TI  - A severe case of tetracycline-induced intracranial hypertension.
AB  - Tetracykline is a first-line treatment of the common skin disorder acne vulgaris.
      A rare side effect of tetracycline treatment is intracranial hypertension also
      called pseudotumor cerebri (PTC). We report a severe case of PTC with cranial
      nerve palsy and visual loss in a 16 year old girl following acne vulgaris
      treatment with tetracycline. 

PMID- 25386254
TI  - The important role of interdisciplinary collaboration in the management of a
      melanocytic skin lesion.
AB  - One of the most confounding characteristics, commonly seen in malignant, but even
      in benign melanocytic nevi, is represented by the regression phenomenon. The
      identification of regression, through dermoscopical observation, can be
      predictive of a tricky histopathological examination. Therefore, this feature
      should be an alert to a meticulous clinical, dermoscopical and histopathological
      correlation for correct analysis of melanocytic skin lesions. A 26-year-old man
      was referred to our department for a pigmented skin lesion localized on his
      trunk. It was clinically and dermoscopically diagnosed as atypical melanocytic
      nevus with central regression. After 1 year the lesion underwent considerable
      changes, leading to a nearly complete regression. The lesion was excised and, on
      the basis of clinical, dermoscopical and histopathological correlation, was
      interpreted as a junctional melanocytic nevus with regression. In our case the
      association of clinical, dermoscopical and histopathological experience, resulted
      an important and useful method, in order to proper interpret and correctly
      diagnose an atypical melanocytic skin lesion. 

PMID- 25386255
TI  - Chronic lymphoedema caused by recurrent infections in a patient with allergic
      hand eczema.
AB  - Allergic contact dermatitis is very common and may be complicated by secondary
      infections. Chronic lymphoedema is a potentially debilitating condition, which
      may occur due to secondary infections or the dermatitis itself. The problem of
      chronic lymphoedema following allergic contact dermatitis has been infrequently
      reported. We report a case of a 47-year-old woman with severe allergic contact
      dermatitis complicated by chronic, intractable lymphoedema of the hands and
      forearms. This case report reminds us that allergic hand dermatitis may be
      complicated by a chronic and debilitating state of lymphoedema. Also, it
      underlines the importance of fast and adequate treatment of both the dermatitis
      and the secondary infections. 

PMID- 25386257
TI  - Excess granulation tissue and hair loss following acitretin.
AB  - Retinoids are routinely used in dermatology for various clinical entities
      including acne vulgaris, rosacea, hypertrophic scars, strie distensae, psoriasis,
      disorders of dyskeratinization, cancer prevention and other chronic
      hyperkeratotic disorders. Oral acitretin therapy is effective in the treatment of
      psoriasis normalizing cellular differentiation and maturation but clinical side
      effects are reported. We describe the occurrence of excess granulation tissue in
      the nails sulcus and noncicatricial universal alopecia in a psoriatic patient
      receiving oral acitretin. 

PMID- 25386256
TI  - Telangiectasia macularis eruptiva perstans: more than skin deep.
AB  - Systemic mastocytosis is a rare disease involving the infiltration and
      accumulation of active mast cells within any organ system. By far, the most
      common organ affected is the skin. Cutaneous manifestations of mastocytosis,
      including Urticaria Pigmentosa (UP), cutaneous mastocytoma or telangiectasia
      macularis eruptive perstans (TMEP), may indicate a more serious and potentially
      life-threatening underlying disease. The presence of either UP or TMEP in a
      patient with anaphylactic symptoms should suggest the likelihood of systemic
      mastocytosis, with the caveat that systemic complications are more likely to
      occur in patients with UP. TMEP can usually be identified by the typical
      morphology, but a skin biopsy is confirmative. In patients with elevated tryptase
      levels or those with frequent systemic manifestations, a bone marrow biopsy is
      essential in order to demonstrate mast cell infiltration. Further genetic testing
      for mutations of c-kit gene or the FIP1L1 gene may help with disease
      classification and/or therapeutic approaches. Rarely, TMEP has been described
      with malignancy, radiation therapy, and myeloproliferative disorders. A few
      familial cases have also been described. In this review, we discuss the clinical
      features, diagnosis and management of patients with TMEP. We also discuss the
      possible molecular pathogenesis and the role of genetics in disease
      classification and treatment. 

PMID- 25386258
TI  - Becker nevus on the neck with ear involvement.
AB  - This is a concise observation of Becker nevus located on the right side of the
      neck with involvement of the ear. 

PMID- 25386259
TI  - Garlic in dermatology.
AB  - Garlic (Allium sativum L. fam. Alliaceae) is one of the best-researched, best
      selling herbal remedies and is also commonly used for treating various health
      problems. Garlic is widely known for its biological properties and plays an
      important role as an antioxidant. The purpose of this review is to gather and
      summarize all dermatologic-oriented in vitro and in-vivo experiments and clinical
      trials on garlic preparations. Extensive literatures search was carried out and
      twenty three studies were included. The results suggest that oral administration
      of garlic is effective on immunologic properties, cutaneous microcirculation,
      protection against UVB and cancer treatment. Additionally, topical application of
      garlic extract can potentially be effective on psoriasis, alopecia areata, keloid
      scar, wound healing, cutaneous corn, viral and fungal infection, leishmaniasis,
      skin aging and rejuvenation. Clinical effectiveness of oral and topical garlic
      extract is not sufficiently and meticulously explored as so far. 

PMID- 25386260
TI  - Cumulative life damage in dermatology.
AB  - Cumulative life damage is an old concept of considerable face validity, which has
      attracted more scientific interest in the fields of sociology and psychology than
      in medicine over the years. The research examines the interconnectivity of the
      many factors which shape the development of individuals or institutions over
      time. By focussing on time, context and process, life course research highlights
      the different effects seemingly similar events may have at different points in
      time and in different contexts. 

PMID- 25386261
TI  - Dermatologists wearing white coats on practice websites: current trends.
AB  - Physicians wearing white coats are perceived as having more authority, being more
      friendly and being more attractive than those not wearing white coats, and
      patients report that they prefer their dermatologist to wear a white coat. The
      aim of the study was to determine the prevalence of dermatologists wearing white
      coats on practice websites. We searched Google for dermatology practice websites
      in six states representing distinct geographic regions in the United States. The
      first one hundred search results were evaluated, and photographs of
      dermatologists on these websites were examined for the presence or absence of
      white coats. Most (77%) of dermatologists did not wear white coats. The highest
      prevalence was in the eastern states of Massachusetts and South Carolina, with
      29% and 39%, respectively. Colorado had the lowest rate at 13%. Rates were
      essentially equal when segmented by gender. Although patients report that they
      prefer their dermatologist to wear a white coat, dermatologists often do not wear
      a white coat on their practice websites. 

PMID- 25386262
TI  - Focal dermal hypoplasia in a male.
AB  - Focal dermal hypoplasia (FDH) is a rare mesoectodermal dysplasia syndrome
      characterized by cutaneous, skeletal, dental, ocular and soft-tissue defects. An
      X-linked dominant mode of inheritance with lethality in male subjects has been
      proposed. Only around 30 cases of FDH have been reported in male subjects. Live
      born affected males are mosaic for mutations in PORCN gene . We present the
      mosaic pattern of FDH in a young boy. 

PMID- 25386263
TI  - Pyoderma Gangrenosum and lymph nodes tuberculosis disease: unusual association.
AB  - Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis with unknown
      etiology. PG associated with infectious disease is very unsual. We report a
      singular case of PG with lymph nodes tuberculosis disease. 

PMID- 25386265
TI  - Autosomal recessive hypotrichosis simplex with woolly hair: a report of a new
      family.
AB  - Autosomal recessive hypotrichosis simplex with woolly hair is a rare
      dermatological disorder, characterized by sparse hair and tightly curled hair. We
      report on a new family affected with this disorder which has not previously been
      reported. In this family, 2 siblings were affected. We believe that the disorder
      is not rare, but is possibly misdiagnosed, and hence underreported. 

PMID- 25386264
TI  - Online videos to promote sun safety: results of a contest.
AB  - Seventy-percent of Americans search health information online, half of whom
      access medical content on social media websites. In spite of this broad usage,
      the medical community underutilizes social media to distribute preventive health
      information. This project aimed to highlight the promise of social media for
      delivering skin cancer prevention messaging by hosting and quantifying the impact
      of an online video contest. In 2010 and 2011, we solicited video submissions and
      searched existing YouTube videos. Three finalists were selected and ranked.
      Winners were announced at national dermatology meetings and publicized via a
      contest website. Afterwards, YouTube view counts were monitored. No increase in
      video viewing frequency was observed following the 2010 or 2011 contest. This
      contest successfully identified exemplary online sun safety videos; however,
      increased viewership remains to be seen. Social media offers a promising outlet
      for preventive health messaging. Future efforts must explore strategies for
      enhancing viewership of online content. 

PMID- 25386266
TI  - Bacterial colonization of psoriasis plaques. Is it relevant?
AB  - Bacterial colonization was investigated retrospectively in patients with plaque
      psoriasis (n=98 inpatient treatments, n=73 patients). At least one pathogen was
      found in 46% of all cases. Staphylococcus aureus was the most frequent bacterium.
      Bacterial colonization of psoriasis plaques could be relevant in individual
      cases. 

PMID- 25386267
TI  - Eruptive keloids after chickenpox.
AB  - Hypertrophic scars and keloids result from abnormal wound healing in predisposed
      individuals. They occur within months of cutaneous trauma (surgical wounds,
      piercing, lacerations) or inflammation (acne, folliculitis, vaccination site).
      They have rarely been reported after chickenpox. Herein we report a dramatic case
      in a 4-year-old black girl and discuss the issues related to the management of
      hypertrophic scars and keloids in this peculiar situation. 

PMID- 25386268
TI  - Zosteriform morphea: Wolf's isotopic response in an immunocompetent patient.
AB  - We report the case of a 19-year old female who presented to our dermatological
      clinic with hyperpigmented, indurated and atrophic patches on a zosteriform
      distribution, extending from her left submammary region through to her back. Our
      case was consistent with a zosteriform morphea as an expression of an isotopic
      Wolf response following an episode of herpes zoster. We discuss the pathogenic
      mechanisms and review the clinical cases previously reported in the literature. 

PMID- 25386269
TI  - Ulcerated cutaneous epithelioid hemangioendothelioma in an 8-month old infant.
AB  - Epithelioid hemangioendothelioma is an uncommon malignant vascular tumour usually
      involving soft tissue and rarely only skin. It is considered to be a borderline
      neoplasm between angiolymphoid hyperplasia with eosinophilia and an epithelioid
      angiosarcoma and is mostly found in adults with few cases reported in children.
      We herein report a case of ulcerated cutaneous epithelioid hemangioendothelioma
      in an infant of 8 months. This tumour has not been reported at such a young age
      in literature. 

PMID- 25386270
TI  - Epidemiologic and clinicopathologic aspects of Leprosy in Dakar; evaluation of 73
      new cases.
AB  - Hundreds of new leprosy cases are still diagnosed in Dakar despite all the
      efforts in the struggle by the national program for elimination of leprosy by the
      Institute of Applied Leprosy in Dakar. The aim of our study was to evaluate the
      epidemiological, clinicopathological and outcome of new cases of leprosy. A
      prospective study was conducted over a period of one year listing all new cases
      of leprosy based on clinical diagnosis, bacteriology and histology. 73 new cases
      were recorded. The sex ratio was 1.5 and the mean age of 39.5 years. Children
      aged from 0 to 15 years old represented 12%. The clinical forms were rated in
      order of decreasing frequency Borderline 47.94%, 30.13% lepromatous lepromatous,
      indeterminate 8.21, borderline lepromatous 6.84, TT: 5.47%, 1.36 and neurological
      bb%. Neurological signs were enlarged nerve in 50 cases, a neurological deficit
      in 16 cases and a sensitive deficit in 16 cases. The complications were burns and
      ulcerations in 10 cases, a claw in 7 cases, a reversal reaction in 7 cases,
      erythema nodosum in 4 cases and neuritis in 8 cases. The number of new cases
      mutilated was 24.65%. The smear was positive in 42% and histology contribution in
      91.37% of cases. Our study highlights the significant number of patients with
      multibacillary contagious, affected children, the high proportion of disability
      grade 2/OMS reflecting the delay in diagnosis. This delay is due to ignorance, to
      traditional treatments and low socio-economic status and lack of trained
      diagnostic teams in different areas apart from referral centres. 

PMID- 25386271
TI  - A new combination of multiple autoimmune syndrome? Coexistence of vitiligo,
      autoimmune thyroid disease and ulcerative colitis.
AB  - The occurrence of three or more autoimmune disorders in one patient defines
      multiple autoimmune syndrome. The pathogenesis of multiple autoimmune syndrome is
      not known yet and environmental triggers and genetic susceptibility have been
      suggested to be involved. Herein, we report a 47-year-old woman who had
      Hashimoto's thyroiditis, vitiligo and newly diagnosed ulcerative colitis.
      Diagnosis of ulcerative colitis was confirmed with histopathologic examination.
      This case presents a new combination of multiple autoimmune syndrome. 

PMID- 25386272
TI  - Primary bilateral malignant melanoma of the lower limbs.
AB  - Malignant melanoma is the eighth most common cancer in European women. Its
      incidence is increasing rapidly and it has been demonstrated that this is related
      to sun exposure. Although few cases of bilateral uveal or choroidal melanoma are
      described in literature, there are no cases reporting bilateral cutaneous
      malignant melanoma. We report a singular case of a 43-year-old woman with two
      primary bilateral melanomas localized on the flexural surface of both legs. 

PMID- 25386273
TI  - Flagellate dermatitis following consumption of shiitake mushroom.
AB  - Japanese dermatologists were the first to describe the very characteristic
      flagellate dermatitis following consumption of undercooked or raw shiitake
      mushroom (Lentinus edodes). These similar eruptions were also reported in
      patients treated with bleomycin, in dermatomyositis and adult onset Still's
      disease. We report a case where a 40 year old chinese female developed flagellate
      dermatitis following ingestion of a bun containing shiitake mushroom. 

PMID- 25386274
TI  - The appearance of angiolipomatosis after using laptop computer on the thighs: a
      relationship?
AB  - A 56-year-old patient developed angiolipomatosis of the anterior part of the
      thighs after repeated laptop contact localisation. Histological findings exhibit
      an unusual inflammatory infiltrate. We postulate that the computer could favour
      lipoma development by a physiopathological mechanism that remains to be
      clarified. 

PMID- 25386275
TI  - Patient with giant Becker's nevus and epidermal nevus.
AB  - Becker's nevus is a cutaneous hamartoma that may be present at birth, but more
      commonly is noticed during puberty. It classically manifests unilaterally on the
      shoulder and upper trunk as a tan to brown patch or thin plaque. "It typically
      has an irregular margin, breaks up into islands at the periphery, and has an
      average size of 125 square centimeters. Numerous skin, soft-tissue, and bony
      anomalies have been reported in association with Becker's nevus. We describe a
      patient with Becker's nevus of considerable size who has a concurrent epidermal
      nevus. 

PMID- 25386276
TI  - Callosity of ankles among people with the habit of sitting with crossed legs: a
      cosmetic problem.
AB  - Many people living in developing countries still prefer to sit on the carpet or
      uncarpeted floor, and many times they sit in a cross legged position. Continuous
      rubbing and friction of the ankles over the carpet or the plain hard surface may
      cause callosity of the ankles. This can cause a cosmetic problem. We describe a
      case series of ankle hyperkeratosis referred to our outpatient clinic in Ahwaz in
      the south west of Iran from 2005-2010. These patients had localized
      hyperkeratosis on two ankles or the front of ankles. This article aims to help
      the clinician become more familiar with the morphological characteristic of this
      problem which may occur in people of Eastern origin. 

PMID- 25386277
TI  - Benign lichenoid keratosis: an off-center fold case.
AB  - This off-center fold case depicts the difficult differential diagnosis for benign
      lichenoid keratosis. It is challenging to diagnosis this benign lesion through
      clinical exam, dermoscopy, and even dermatopathology. Given its similar
      appearance to regressed melanoma, it is important to be cognizant of both and up
      to date on the dermatopathology clues. 

PMID- 25386278
TI  - Dermoscopy of keratosis follicularis squamosa.
AB  - Although the characteristic clinical appearance and the differences in
      distribution, it is often difficult to differentiate keratosis follicularis
      squamosa (Dohi) from other keratotic disorders. Here, we describe the case of a 5
      year-old boy with Dohi in the first time that by using dermoscopy. Dermoscpoy of
      the lesion showed typical lotus leaves on the water appearance and follicular
      plug in the center. We reported the usefulness of dermosocopy in Dohi. 

PMID- 25386279
TI  - Lichen sclerosus et atrophicans, scleroderma en coup de sabre and Lyme
      borreliosis.
AB  - Lichen sclerosus et atrophicans (LSA) is a chronic, inflammatory skin disease of
      unknown etiology, characterized by atrophy. We report a case of LSA with
      frontoparietal distribution, mimicking scleroderma en coup de sabre, causing
      scarring alopecia. The case was associated with Borrelia infection. The lesion
      improved with 2 cycles of antibiotic therapy with ceftriaxone 2 gr/day i.v for 21
      days associated with UVA-1 therapy and local and systemic vitamin E supply (400
      mg 2x/day per os for 3 months). This case stresses the importance of identifying
      clinical manifestations associated with Lyme disease and the use of tissue PCR to
      detect borrelial DNA in patients with these lesions, but characterized by
      negative serology for Borrelia. 

PMID- 25386280
TI  - Laser therapy for Hailey-Hailey disease: review of the literature and a case
      report.
AB  - Medical therapy for Hailey-Hailey disease (HHD) generally only provides temporary
      suppression. Surgical intervention has been shown to prolong remission, but may
      lead to significant morbidity. Laser therapy is becoming the preferred method of
      treatment because of its successful results and lower risk of complications
      compared to surgical modalities. We report a case of fractional ablative carbon
      dioxide (CO2) laser treatment for HHD and review the relevant literature.
      Fractional CO2 laser therapy was performed in our patient with a 14-year history
      of HHD. No recurrence was observed 5 months after laser therapy in right
      inframammary and axillary regions. Symptomatic recurrence was noted after
      treatment of inguinal areas. In conclusion, traditional laser ablation remains
      the treatment of choice for prolonged remission of recalcitrant plaques in HHD. 

PMID- 25386281
TI  - Papulonecrotic tuberculid: report of a clinical case.
AB  - Papulonecrotic tuberculid is a rare, chronic, recurrent and symmetric eruption of
      necrotizing skin papules arising in crops, involving primarily the limbs. It
      occurs in less than 5% of active tuberculosis. Typically bacilli are not detected
      in any of the cutaneous lesions. Extracutaneous tuberculosis primary focus is
      only detected in 30-40% of the cases, being the lymph nodes the most common
      location. Antituberculosis treatment is rapidly effective and is often the main
      confirmation of the diagnosis. 

PMID- 25386282
TI  - Tegafur-induced acral hyperpigmentation.
AB  - Tegafur is a prodrug of 5-fluorouracil (5-FU) with a similar spectrum of
      antitumor activity. It is used in the treatment of advanced gastrointestinal
      neoplasms. Over 5-FU, tegafur has the advantage of oral administration and less
      hematologic toxicity. Gastrointestinal toxicity is its main dose-limiting factor.
      The cutaneous adverse effects of tegafur include mucositis, photosensitivity,
      diffuse or nail-restricted hyperpigmentation, palmoplantar erythrodysesthesia
      syndrome, palmoplantar keratoderma, sclerodactyly and Raynaud phenomenon. We
      report here the case of a patient who developed acral hyperpigmentation during
      treatment with tegafur. 

PMID- 25386283
TI  - Lichenoid drug eruption due to eprosartan/hydrochlorothiacide.
AB  - We report a case of a 66-year-old male who developed an itchy eruption while
      taking an antihypertonic drug containing eprosartan and hydrochlorothiacide after
      sun exposure. The lesions resembled a lichenoid appearance that was confirmed by
      the histological study. There are few reports in the literature of lichenoid
      reactions to these compounds, so we review the characteristics of themselves as a
      potencial cause of drug eruptions. 

PMID- 25386284
TI  - Eczema herpeticum in pregnancy.
AB  - Eczema herpeticum (EH), or Kaposi's varicelliform eruption, is a skin infection
      with herpes simplex type I virus (HSV-1) that occurs in patients with compromised
      skin integrity, such as atopic dermatitis (AD). Unrecognized, it may be fatal and
      viremia in pregnancy may lead to fetal demise and miscarriage. We describe a rare
      case of EH in pregnancy, eczema herpeticum gravidarum (EHG), which is the third
      published report in the literature to date. 

PMID- 25386285
TI  - Coexistence of reticulate acropigmentation of Kitamura and Dowling-Degos disease.
AB  - Reticulate acropigmentation of Kitamura (RAK) and Dowling-Degos Disease (DDD) are
      rare genodermatosis inherited as an autosomal dominant trait with variable
      penetrance. They are part of a spectrum of diseases with hyperpigmented macules
      coalescing in a reticular pattern, facial and palmoplantar pits, breaks in
      dermatoglyphics, comedo-like lesions and epidermoid cysts, and a unique
      histological picture of hyperpigmented digitate epidermal downgrowths. The
      authors describe the case of a 45-year-old female with reticulate
      acropigmentation of the dorsa of the hands and feet, hyperpigmented macules on
      the axilla and around the mouth, and palmar pitting. Clinical and histological
      findings, together with a relevant family history, allowed the authors to
      consider this case an example of the rare event of an overlap RAK-DDD. 

PMID- 25386286
TI  - Karl Gustaf Torsten Sjogren and Sjogren-Larsson syndrome.

PMID- 25386287
TI  - Unilateral Blaschkoid lichen planus in successive pregnancies.
AB  - A number of genetic, congenital and acquired dermatoses have been known to follow
      Blaschko's lines. A common disorder like lichen planus can very rarely present
      with pruritic lesions in atypical patterns such as unilateral distribution,
      painful eruptions and along Blaschko's lines. Various triggering factors varying
      from viral infections and vaccinations to trauma have been implicated in lichen
      planus. We describe a female patient in the second trimester of her second
      pregnancy who developed unilateral lichen planus along Blaschko's lines during
      both pregnancies. No case of lichen planus along Blaschko's lines recurring
      during pregnancy is reported so far. Could pregnancy itself be a contributory
      factor towards onset of lichen planus in this case? 

PMID- 25386288
TI  - Ellagic acid inhibits melanoma growth in vitro.
AB  - Ellagic is a polyphenolic compound with anti-fibrotic and antioxidant properties,
      and exhibits antitumor properties against various cancer cells in vitro. There
      are few studies, however, which examine the effects of ellagic acid on melanoma.
      In the present study, we observe effects of ellagic acid on melanoma cells in
      vitro. Three metastatic melanoma cell lines (1205Lu, WM852c and A375) were
      examined to determine the effects of ellagic acid on melanoma cell viability,
      cell-cycle, apoptosis, NF-kappabeta activity, and IL-1beta & IL-8 secretion. Cell
      viability assays demonstrated that ellagic acid possesses an inhibitory effect on
      cell proliferation at concentrations between 25 and 100 uM. In addition, ellagic
      acid promoted G1 cell cycle arrest, increased levels of apoptosis and decreased
      synthesis of IL-1beta and IL-8 in melanoma cells. Ellagic acid also decreased NF
      kappabeta activity, suggesting at least one potential mechanism by which ellagic
      acid may exert its effects in melanoma cells. Our findings support further
      investigation into prospective roles for ellagic acid as a therapeutic, adjuvant,
      or preventive agent for melanoma. 

PMID- 25386289
TI  - Vulvar basal cell carcinoma: report of a case involving the mucosa and review of
      the literature.
AB  - We report the case of woman who presented a vulvar basal cell carcinoma (BCC) on
      the inner part of the labium majus, treated with local resection. Vulvar BCC is a
      rare cancer but can be long misdiagnosed due to a non-specific presentation.
      Though even rarer, BCC involving the mucosal side of the labium majus has to be
      considered in the differential diagnosis of the vulvar tumors. A complete
      excision with free margins is the treatment most recommended. Other
      recommendations include the early identification of aggressive subtypes, which
      carry a greater risk of recurrence and spreading potential as well as a long-term
      follow-up with exhaustive muco-cutaneous examination. 

PMID- 25386290
TI  - Epidermolysis bullosa acquisita: current diagnosis and therapy.
AB  - Epidermolysis bullosa acquisita (EBA) is an acquired, autoimmune subepidermal
      blistering disease with an approximate prevalence of 0,2/million people. The
      hallmark of EBA is the presence of autoantibodies (mainly IgG class) to anchoring
      fibril collagen (type VII collagen) located at the dermal-epidermal junction.
      Clinically EBA is subdivided into the inflammatory and the non-inflammatory
      phenotypes, depending on the level of the cleavage in the basal membrane. A
      recent addition to the diagnostic techniques is the analysis of the serration
      pattern of the autoantibody deposits at the basal membrane in the direct
      immunofluorescence. EBA and the closely related bullous systemic lupus
      erythematosus are the only diseases presenting with the so-called u-serration
      pattern which distinguishes them from many other autoimmune subepidermal
      blistering diseases. We also discuss the recent advances in therapy, including
      the experience with Rituximab. 

PMID- 25386291
TI  - Cutaneous plasmacytosis: a case report and review of pulmonary findings.
AB  - Primary cutaneous plasmacytosis is an uncommon cutaneous disorder with multiple
      cutaneous nodules and plaques mainly on face and trunk. This entity is thought to
      be a reactive process with unknown etiology. Pulmonary involvement could be found
      as a part of systemic plasmacytosis whereas cutaneous plasmacytosis was also
      reported with other pulmonary disorders. This report presents the case of
      cutaneous plasmacytosis and the review of pulmonary findings reported in
      plasmacytosis. 

PMID- 25386292
TI  - Infliximab-induced intertriginous psoriasis in patient with Crohn's disease.
AB  - Tumor necrosis factor-alpha (TNFalpha) inhibition is an effective treatment of
      moderate-to-severe psoriasis and other diseases (rheumatoid arthritis, ankylosing
      spondylitis, psoriasis or Crohn's disease). We report a case of a 32-years-old
      patient affected by Crohn's disease since the age of 25 who started infliximab
      infusion after four years of treatment with prednisone and azathioprine per os
      without improvement. After the fifth infusion of infliximab, he developed a form
      of intertriginous psoriasis which was approached with topical steroid cream. The
      patient never presented psoriasis in the past. New onset of psoriasis in patients
      without history for skin diseases (as in our case) is a quite uncommon
      complication of TNFalpha inhibitor therapy. The increased production of IFNalpha
      during TNFalpha inhibitor therapy is a possible pathophysiologic explanation for
      this paradoxical effect of the anti-TNFalpha. 

PMID- 25386293
TI  - Hyperimmunoglobulin E syndrome in two siblings.
AB  - Hyperimmunoglobulin E recurrent infection syndrome (HIES) is characterized by
      recurrent skin and lung infections, eczema, elevated serum immunoglobulin E (IgE)
      levels (>2000 IU/mL), various connective tissue, skeletal, and vascular
      abnormalities.(1) We describe herein two brothers with HIES and documented the
      complications and management of such involvement. 

PMID- 25386294
TI  - Unilateral linear syringoma in a Japanese female: dermoscopic differentiation
      from lichen planus linearis.
AB  - A dermoscopy of linear unilateral syringoma has never been described in the
      English literature. The authors report the case to elucidate the dermoscopic
      features of syringoma. Clinical, dermoscopic and pathological features of a 38
      year-old Japanese female case of linear unilateral syringoma on the left upper
      arm were described and compared with those of lichen planus linearis. Although
      the clinical appearance of linearly arranged dusky erythemas in the present case
      was quite similar to that of lichen planus linearis, dermoscopy did not show
      Wickham's striae but rather homogeneous light brown pigmentation with multifocal
      whitish areas and a delicate pigment network at the periphery. Dermoscopy might
      be helpful to differentiate linear unilateral syringoma from lichen planus
      linearis. 

PMID- 25386295
TI  - Narrowband UVB-induced lichen planus pemphigoide.
AB  - Lichen planus pemphigoides (LPP) is an autoimmune disease characterised by
      evolution of subepidermal blisters on normal and lichen planus affected skin. We
      describe a case of LPP in a 54-year-old Chinese woman. The patient presented with
      psoriasiform plaques and was diagnosed with guttate psoriasis. Narrowband
      ultraviolet B (NBUVB) therapy was commenced, and she experienced a generalised
      eruption of violaceous papules, bullae over the lower limbs, and Wickham's striae
      over the buccal mucosa. Histology from a plaque revealed interface dermatitis,
      while a specimen from a blister showed subepidermal bulla. Direct
      immunofluorescence showed linear deposition of IgG and C3 along the basement
      membrane. A diagnosis of LPP was made on clinicopathological grounds. This is the
      first case report of NBUVB alone in unmasking LPP. In this case report, we
      describe the pathological mechanism of NBUVB in the development of LPP and key
      features distinguishing LPP from bullous lupus erythematosus, bullous lichen
      planus, bullous pemphigoid, and psoriasis. 

PMID- 25386296
TI  - Wegener's granulomatosis in a young patient preceded by localized cutaneous
      manifestations.
AB  - Wegener's granulomatosis (WG) is a rare, systemic vasculitis involving multiple
      organs. The clinical presentation is highly diverse, and there is considerable
      risk of mortality if diagnosis and treatment are delayed. We present a case
      illustrating that patients with WG may initially present with localized cutaneous
      symptoms and signs. 

PMID- 25386297
TI  - A giant benign clear cell hidradenoma on the anterior trunk.
AB  - Clear cell hidradenoma (CCH) is an uncommon variant of benign cutaneous adnexal
      tumors. These tumors are clinically asymptomatic, solitary dermal nodules. They
      occur most frequently on the scalp, face abdomen and extremities. Growth is slow
      and malignant change is rare. 45-year-old woman presented with a nodule which had
      begun 4 years ago as a small nodular asymptomatic lesion and had a central
      ulceration and a minimal hemorrhagic discharge on her anterior abdomen wall. On
      dermatologic examination there was a 6.5*5*4 cm non-tender, soft reddish purple
      nodule, with lobular appearance and ulceration. In the laboratory investigations,
      all hematologic and biochemical tests were normal. A computed tomography (CT)
      scan demonstrated a cystic tumor with lobulated contour with contrast
      enhancement. The lesion was excised totally. In histopathological examination,
      the tumor was composed of biphasic smaller dark polygonal cells and larger clear
      cells and coarse nuclear chromatine. There were duct like structures.
      Immunohistochemical investigation was done for the suspicion of malignancy.
      Cytoplasm of clear cells and of duct like structures showed PAS-positive and d
      PAS resistant staining. There was a positive reaction to epithelial membrane
      antigen and carcinoembryonic antigen. The mitotic index in Ki 67 examination was
      low. All these findings confirmed the diagnosis of benign CCH. 

PMID- 25386298
TI  - Lichen planus pigmentosus-like ashy dermatosis.
AB  - Ashy dermatosis, also known as erythema dyschromicum perstans, is an idiopathic
      dermal melanosis of unknown etiology. We here describe an unusual case of 63-year
      old Caucasian male with ashy dermatosis and skin lesion of lichen pigmentosus
      like. No treatment was tried because the lesions were totally asymptomatic. After
      a control, three months later, all lesions had cleared up. This case is of
      interest because it proves the existence of ashy dermatosis with clinical aspect
      lichen planus pigmentosus-like. This is the first case in the literature of
      lichen planus pigmentosus-like ashy dermatosis confirming the view that ashy
      dermatosis is a variant of lichen planus without the typically band-like
      infiltrate and Max Joseph spaces. 

PMID- 25386299
TI  - Pseudolymphoma tattoo-induced.
AB  - Tattooing has become more and more popular in today's society. The most common
      dermatological tattoo complications are represented by hypersensitivity reaction
      to tattoo pigments like irritant and allergical contact dermatitis, development
      of lichenoid areas and granulomatous responses, such as sarcoid granulomas or
      foreign body granulomas. Less frequently patients developing discoid lupus
      erythematous have been reported. Pseudolymphoma is an uncommon reactive
      lymphocytic proliferation mimicking the histological and clinical features of a
      malignant skin lymphoma. We herein report a pseuldoymphoma limited to the red
      area of a multicolour tattoo of the leg. 

PMID- 25386300
TI  - Lupus erythematosus and lichen planus overlap syndrome:a case report with a rapid
      response to topical corticosteroid therapy.
AB  - Lupus erythematosus (LE) and lichen planus (LP) may occur as an overlap syndrome.
      We report the clinical characteristics of a young man with lesions diagnosed as
      LE and LP by histopathological and direct immunoflurosence examinations. We
      achieved remarkable clinical response from the treatment with topical
      corticosteroids and no recurrence was seen in a 6 months of follow up time. We
      found this case interesting because of the rapid improvement with corticosteroid
      and discussed if there is a real overlap or a coexistence according to the
      literature. 

PMID- 25386301
TI  - Churg-Strauss syndrome and hemorrhagic vasculitis.
AB  - Churg-Strauss syndrome (CSS) is a rare syndrome characterized by sinusitis,
      asthma and peripheral eosinophilia. This vasculitic syndrome affects medium and
      small-sized vessels, the lung being the most commonly affected organ, followed by
      the skin. The authors report a case of a 59-year-old male with a past history of
      asthma and allergic rhinitis. He presented necrohemorragic lesions in the distal
      phalanx of the 2(nd), 3(rd) and 4(th) fingers of the left-hand and petechial
      lesions in the plant of both feet, accompanied by asthenia, anorexia and weight
      loss. The analytical study revealed leukocytosis with eosinophilia, elevated
      inflammatory parameters and p-ANCA positive antibodies. The diagnosis of CSS was
      established based on clinical and histopathological data. Cutaneous
      manifestations of hemorragic vasculitis are rare in CSS syndrome but can be the
      first manifestation of the disease. The recognition of this presentation is
      important for the early diagnosis and treatment of this syndrome. 

PMID- 25386302
TI  - Atypical piloleiomyoma of the face presenting with central ulceration.
AB  - Piloleimyoma is a type of cutaneous leiomyoma arising from arrectores pilorum. It
      can present as either a solitary nodule or multiple lesions. Usually it is
      localized on the extremities, but can also occur on trunk, neck area and face.
      Lesions are usually cold, ulcerated and spontaneously painful. Herein we report a
      case of piloleiomyoma with cytological atypia that was painless despite the
      presence of central ulceration. 

PMID- 25386303
TI  - Cutaneous lesions as presentation form of mantle cell lymphoma.
AB  - Mantle cell lymphoma is a type of non-Hodgkin lymphoma that affects extranodal
      areas, especially, bone narrow, digestive tract and Waldeyer ring. Here we report
      a case of mantle cell lymphoma IV Ann Arbor stage with cutaneous lesions on nasal
      dorsum and glans penis as the first manifestations. Skin involvement is a very
      rare manifestation and less than 20 cases have been reported in the literature.
      The importance of establishing multidisciplinary relationships for a global
      approach has been shown by this clinical case. 

PMID- 25386304
TI  - Generalized mid dermal elastolysis.
AB  - Mid-dermal elastolysis (MDE) is a rare skin disorder clinically characterized by
      the appearance of diffuse fine wrinkling, most often of the trunk and arms. This
      entity is distinguished from other elastolytic disorders by its characteristic
      selective loss of elastic fibers of the mid dermis. The aetiopathogenesis of the
      disease is still unclear as well as the effective treatment. Half of the cases
      described in the literature are associated with ultraviolet radiation exposure.
      Other reported triggering conditions such as urticaria, eczema and granuloma
      annulare suggests different eliciting inflammatory pathways. The authors describe
      the case of a 38-year-old woman who developed an urticarial eruption during
      months which progressed to generalized and severe fine wrinkling. 

PMID- 25386305
TI  - Bullous mycosis fungoides associated with an extensive ulcer and a severe
      leukemoid reaction.
AB  - This report presents a case of bullous mycosis fungoides associated with an
      extensive ulcer and a severe leukemoid reaction. The rash began as indurated
      erythema which was always followed by ulceration. The rashes initially responded
      to radiation therapy, but multiple recurrences appeared. Several bullae appeared
      on the trunk during the course of the illness, without any evidence of
      paraneoplastic pemphigus. Finally, the ulcer covered a large part of the trunk,
      and the patient died of sepsis with an extreme leukocyte count of 118,000/uL. A
      bone marrow analysis revealed a leukemoid reaction and an autopsy revealed
      pseudomembranous colitis. 

PMID- 25386306
TI  - Long-term safety, tolerability, and efficacy of vismodegib in two patients with
      metastatic basal cell carcinoma and basal cell nevus syndrome.
AB  - Tumor responses in advanced basal cell carcinoma (BCC) have been observed in
      clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism
      is inhibition Hedgehog Signaling Pathway (HHSP) downstream target genes. HHSP
      inhibition has been shown to affect stem cells responsible for blood, mammary,
      and neural development. We report on our experience of treating two patients with
      advanced BCC participating. These two patients have had no new BCCs develop for
      at least 2.25 years. Both patients have been receiving ongoing daily treatment
      with vismodegib for greater than 2.75 years without experiencing any significant
      side effects. After prolonged continuous daily dosing with a SMO antagonist, we
      have not observed a significant alteration in hematologic parameters or physical
      abnormalities of the pectoral regions of two patients with advanced BCC. 

PMID- 25386307
TI  - Resolution of Cullen's sign in patient with metastatic melanoma responding to
      hypoxia-activated prodrug TH-302.
AB  - Cullen's sign, ecchymosis of the subcutaneous periumbilical tissue often
      described in association with non-malignant conditions such as ruptured ectopic
      pregnancy or acute pancreatitis, has been reported in malignancies involving the
      abdomen. In melanoma, hematoma-like metastasis has been observed and can resolve
      with an effective therapy. We observed resolution of Cullen's sign (probably
      hematoma-like metastasis) in a patient with metastatic melanoma. The patient was
      participating in a phase I clinical trial and treated with TH-302, a hypoxia
      activated prodrug. After 2 months on study, complete resolution of Cullen's sign
      resolved in concert with extracranial response in lung, liver, and lymph node
      metastases. Based on the dramatic extracranial response to this investigational
      agent, additional patients with metastatic melanoma without evidence of brain
      metastasis were treated on study with TH-302. 

PMID- 25386308
TI  - Combined cetuximab and volumetric modulated arc-radiotherapy in advanced
      recurrent squamous cell carcinoma of the scalp.
AB  - A 77-year old male patient presented with an ulcerated exophytic tumor (T2, N0,
      M0) with three macroscopically visible satellite metastases in the right temporo
      occipital region. Mohs surgery could not control the disease due to lymphangiosis
      carcinomatosa and perineural infiltration, and recurrence of satellite skin
      metastases. Re-staging demonstrated a T2, N1, M0 profile (stage III, AJCC).
      Chemotherapy was limited by the patient's co-morbidities. Therefore, we used
      targeted therapy with monoclonal anti-epidermal growth factor receptor antibody
      cetuximab in combination with volumetric modulated arc- radiotherapy (VMAT).
      Cetuximab was well tolerated except for the loading dose when the patient
      developed fever chills. To verify the correct application of VMAT, it was applied
      to a 3-dimensional measuring phantom prior to the patient's first treatment
      session. To minimize these tolerances, patient set-up was checked and corrected
      by orthogonal fluoroscopic images recorded daily by the on-board imager used in
      our Varian accelerator. The average daily beam time was 6 min (6 arcs, 767
      monitor units); the total treatment time including patient set-up and set-up
      correction was less than 20 min. Combined therapy was well tolerated and complete
      remission was achieved. 

PMID- 25386309
TI  - Atopic dermatitis in adolescence.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disorder that typically
      occurs during childhood especially in the first year of life, with a variable
      frequency from 10% to 30%. Recent studies have shown that in Europe among 10-20%
      of children with AD suffer from this disorder also in adolescence. AD is a
      chronic inflammatory skin disease with a typical onset in the first years of life
      and with a 10-30% prevalence among young children. AD prevalence in adolescence
      has been estimated around 5-15% in European countries. AD persists from childhood
      through adolescence in around 40% of cases and some risk factors have been
      identified: female sex, sensitization to inhalant and food allergens, allergic
      asthma and/or rhinoconjunctivitis, the practice of certain jobs. During
      adolescence, AD mainly appears on the face and neck, often associated with
      overinfection by Malassezia, and on the palms and soles. AD persistence during
      adolescence is correlated with psychological diseases such as anxiety; moreover,
      adolescents affected by AD might have problems in the relationship with their
      peers. Stress and the psychological problems represent a serious burden for
      adolescents with AD and cause a significant worsening of the patients' quality of
      life (QoL). The pharmacological treatment is similar to other age groups.
      Educational and psychological approaches should be considered in the most severe
      cases. 

PMID- 25386310
TI  - Dermatofibrosarcoma protuberans diagnosed by a single biopsy.
AB  - This brief report is about a 9 year old girl presenting with a 2.5 cm circular
      blue to violet discoloration on the anterolateral upper left thigh. The first
      biopsy taken revealed the diagnosis dermatofibrosarcoma protuberans. The patient
      underwent surgery at a specialized sarcoma center with post operative histology
      showing free wide resection margin. Preoperative chest x-ray showed no sign of
      metastasis. This brief report emphasizes the significance of the use of biopsy
      when cutaneous elements look suspicious and diagnosis is unclear. 

PMID- 25386311
TI  - Clinical, dermoscopic and histological features of a combined tumor composed of a
      melanoma in situ, a basal cell carcinoma and an intradermal naevus.
AB  - The combined tumors are neoplasms consisting of 2 or more distinct cell
      population that are intimately admixed. The presence of more than one neoplasm in
      the same lesion comprising melanocytes and keratinocytes are rare but well
      documented. We report a case of a 65-year-old man with a melanoma in situ, a
      basal cell carcinoma and an intradermal naevus in collision that clinically
      appeared as a single lesion. Clinical, dermoscopic and histological features are
      discussed. 

PMID- 25386312
TI  - Defining an acceptable period of time from melanoma biopsy to excision.
AB  - Melanoma is the most lethal form of skin cancer and it is the second most common
      cancer among adolescents and young adults. The aim of this work is to determine
      if surgical intervals differ between four different clinics and between
      departments within the hospitals, and to compare these to industry standards.
      Surgical intervals were measured through retrospective chart review at four
      dermatology clinics. Of 205 melanoma cases, clinic and departmental median
      surgical intervals ranged 15-36.5 days and 26-48 days, respectively. There was
      significant association between clinic and time between biopsy and pathology
      report, time between pathology report and excision, and total surgical interval
      (P<0.0001, P=0.03, and P<0.0001 respectively). There was significant association
      between department and time between pathology report and excision, and surgical
      interval (P<0.0001, and P=0.003 respectively). Pair-wise comparisons detected
      significantly longer intervals between some clinics and departments (maximum
      difference 67.3%, P<0.0001). Hypothesis-based, informal guidelines recommend
      treatment within 4-6 weeks. In this study, median surgical intervals varied
      significantly between clinics and departments, but nearly all were within a 6
      week frame. 

PMID- 25386313
TI  - Psoralen plus ultraviolet A (PUVA) soaks and UVB TL01 treatment for chronic hand
      dermatoses.
AB  - Chronic eczematous hand dermatoses with and without contact allergies are complex
      diseases, which makes it a challenge to select the best treatment and obtain an
      optimal patient experience and a satisfactory treatment result. The aim of this
      study was to evaluate retrospectively the clinical effect and patient experience
      of local treatment with psoralen plus ultraviolet A (PUVA) soaks and TL01
      phototherapy for severe chronic hand dermatoses, and also to evaluate the quality
      of life for the subgroup of patients with allergic contact dermatitis including
      Compositae allergy. A retrospective evaluation of results for 94 consecutive
      patients having received a total of 121 treatment courses with local PUVA soaks
      or TL01 phototherapy for one of the following diagnoses (n=number of treatment
      courses): psoriasis (n=19), hyperk-eratotic hand eczema (n=27), Pustulosis
      Palmoplantaris (PPP) (n=22), vesicular eczema (n=16), Compositae dermatitis
      (n=24), and allergic contact dermatitis (n=13). Moreover, semi-structured
      interviews with 6 selected patients having multiple contact allergies including
      Compositae allergy were used to evaluate quality of life. As a result, we found
      that PUVA soaks has good effect in patients with psoriasis and hyperkeratotic
      hand eczema and local phototherapy for chronic hand dermatoses is a useful
      treatment option in selected cases. 

PMID- 25386314
TI  - Plantar pitted keratolysis: a study from non-risk groups.
AB  - Pitted keratolysis is an acquired, superficial bacterial infection of the skin
      which is characterized by typical malodor and pits in the hyperkeratotic areas of
      the soles. It is more common in barefooted people in tropical areas, or those who
      have to wear occlusive shoes, such as soldiers, sailors and athletes. In this
      study, we evaluated 41 patients who had been diagnosed with plantar pitted
      keratolysis. The patients were of high socioeconomic status, were office-workers,
      and most had a university degree. Malodor and plantar hyperhydrosis were the most
      frequently reported symptoms. The weight-bearing metatarsal parts of the feet
      were those most affected. Almost half the women in the study gave a history of
      regular pedicure and foot care in a spa salon. Mean treatment duration was 19
      days. All patients were informed about the etiology of the disease, predisposing
      factors and preventive methods. Recurrences were observed in only 17% of patients
      during the one year follow-up period. This study emphasizes that even malodorous
      feet among non-risk city dwellers may be a sign of plantar pitted keratolysis. A
      study of the real incidence of the disease in a large population-based series is
      needed. 

PMID- 25386315
TI  - Granulosis rubra nasi: a rare condition treated successfully with topical
      tacrolimus.
AB  - A 20 years-old girl presented with multiple asymptomatic reddish vesicles on face
      for four years. It used to get worse in summer and was associated with localized
      hyperhidrosis. The lesions were notable for disappearance on diascopy.
      Histopathology from the vesicle showed mononuclear cell infiltration in the upper
      dermis, especially around eccrine sweat apparatus, along with dilatation of
      superficial capillaries and lymphatics. Based on clinical presentation and
      histopathology, diagnosis of Granulosis rubra nasi (GRN) was made. GRN usually
      resolves at puberty; however, rarely it may persist in adulthood. We here report
      a case of GRN having lesions persisting in adulthood. Moreover, she showed
      excellent response to topical tacrolimus, a finding not observed in literature. 

PMID- 25386316
TI  - Allergic contact dermatitis from sculptured acrylic nails: special presentation
      with an airborne pattern.
AB  - Methylmethacrylate was first reported in 1941 as a cause of contact dermatitis.
      Since then, occupational contact allergies to acrylates in dentistry, orthopedic
      surgery, printing industry and industry have been reported, but few reports are
      found in the literature as a consequence of the contact with sculptured
      artificial acrylic nails which are increasingly popular. We describe here 3
      patients with contact allergy to acrylates in artificial sculptured nails. Patch
      tests were performed with the Portuguese baseline series of contact allergens and
      an extended series of acrylates were applied. In particular, we tested three
      female patients with allergic contact dermatitis from sculptured acrylic nails.
      Two of these patients were both customers and also technical nail beauticians.
      Two patients developed periungual eczema; one presented only with face and eyelid
      dermatitis had no other lesions. The tests showed positive reaction to 2
      hydroxyethylmethacrylate (2-HEMA) and 2-hydroxypropylmethacrylate (2-HPMA) in all
      the three patients. Our cases demonstrate the variety of clinical presentations
      of allergic contact dermatitis from acrylic sculptured nails. They show the need
      to warn patients of persistent and sometimes permanent side effects of these
      products. They also emphasize the importance of cosmetic ingredient labeling. 

PMID- 25386317
TI  - Polymorphic eruption of pregnancy developing postpartum: 2 case reports.
AB  - Polymorphic eruption of pregnancy (PEP), also known as pruritic urticarial
      papules and plaques of pregnancy, is a common benign dermatosis of pregnancy
      mainly affecting primigravidae and multiple pregnancies. We report here two cases
      of PEP with typical clinical and histological features presenting in the
      postpartum period. 

PMID- 25386318
TI  - Treatment of vitiligo vulgaris with the combination therapy of topical steroid
      and vitamin D3 compound.
AB  - We report here two cases of vitiligo vulgaris successfully treated with the
      combination therapy of topical steroid and vitamin D3 compound and currently
      maintained by vitamin D3 analog without any adverse effects: skin atrophy, striae
      or telangiectasia on the exposed areas. The best-known mechanism of topical
      vitamin D3 analog is the enhancement of keratinocytes differentiation and anti
      proliferative effects. Vitamin D3 analog is also reported to suppress T-cell
      mediated immunity, T-cell skin recruitment, and skin infiltration via down
      regulating cutaneous lymphocyte antigen expression. Furthermore, vitamin D3
      compounds are known to influence melanocyte maturation and differentiation and
      also to up-regulate melanogenesis. Autoreactive lymphocytes against melanocytes
      are one of the causes. Topical vitamin D3 analog may control vitiligo itself,
      however stronger immunosuppressive effects of topical corticosteroid may
      contribute to rapid re-pigmentation suppressing auto-reactive lymphocytes. The
      topical combination therapy is a simple, effective and safe option for vitiligo
      vulgaris in sun-exposed areas. 

PMID- 25386319
TI  - Zosteriform metastases from colon carcinoma: an unusual pattern.
AB  - Cutaneous metastases of internal malignancies occur infrequently and the
      zosteriform spread of the skin lesions represents a rare entity. We report here a
      case of cutaneous metastases from a colon carcinoma clinically mimicked Herpes
      varicella-zoster. The literature is also reviewed. 

PMID- 25386320
TI  - Erythema annulare centrifugum-like eruption associated with pegylated interferon
      treatment for hepatitis C.
AB  - Current standard of treatment for chronic hepatitis C virus infection requires
      the use of pegylated interferon plus ribavirin. Treatment with these two agents
      has been associated with numerous side effects, which frequently include
      dermatologic eruptions. We report a cutaneous eruption associated with interferon
      having clinical presentation of erythema annulare centrifugum. The eruption
      occurred within days of the first interferon injection and repeatedly flared
      following subsequent injections. Our patient was able to continue therapy without
      interruption, while managing the reaction with topical corticosteroid and oral
      antihistamine. We conclude that this is a benign cutaneous eruption associated
      with interferon which can be managed without discontinuing treatment for
      hepatitis C. 

PMID- 25386321
TI  - Late reaction to ustekinumab infusion.
AB  - Psoriasis is a chronic inflammatory disease that directly affects the quality of
      life. Biologics are prescribed for patients unresponsive to conventional
      treatments and with severe forms of the disease. Ustekinumab is a fully human
      monoclonal antibody against the p40 subunit of interleukins 12/23 that is being
      used with satisfactory responses, achieving an improvement in the baseline
      Psoriasis Area and Severity Index of approximately 75% after 12 weeks of
      treatment. It has few side effects, including grater susceptibility to infections
      and development of reactions to the drug. Our report discusses a case of a
      cutaneous reaction to the use of ustekinumab in a 27 year-old male patient after
      the third dose of the medication. No similar case has been reported in the
      literature. 

PMID- 25386322
TI  - Cutaneous horn malignant melanoma.
AB  - A 73-year-old Japanese woman presented with cutaneous horn on the right cheek.
      The resected tumor was 9 mm in diameter, with 14 mm protrusion, and showed
      exophytic growth with marked papillomatosis. Histopathology showed proliferation
      of atypical melanocytes with melanin pigments in the epidermis and dermis under
      the cutaneous horn. These cells were confined to the base of the cutaneous horn,
      and did not spread to the surrounding epidermis. The final diagnosis was
      cutaneous horn malignant melanoma. This pathological entity is considered a
      specific form of verrucous melanoma, and might be added to the list of cutaneous
      horn-forming lesions. 

PMID- 25386323
TI  - Orofacial Granulomatosis in Children can be the Initial Manifestation of Systemic
      Disease: A Presentation of Two Cases.
AB  - Orofacial granulomatosis is a chronic granulomatous condition characterized by
      relapsing and remitting lip swelling and oral involvement that may include deep
      ulcers, tags and cobblestone formation. It occurs as an independent entity but
      also in conjunction with systemic diseases such as tuberculosis, sarcoidosis and
      Crohn's disease. The clinical presentation is not indicative of concomitant
      systemic disease. To highlight the importance of thorough examination to rule out
      systemic disease, we present two childhood cases of orofacial granulomatosis, one
      of which was associated to Crohn's disease. 

PMID- 25386324
TI  - Verrucous lichen planus: a rare presentation of a common condition.
AB  - Lichen planus is a chronic papulosquamous dermatoses in which both skin and
      mucosae are involved. There are various morphological forms of lichen planus.
      Hypertrophic lichen planus is one of the rare clinical variants. Herein, we
      report a very unusual presentation of hypertrophic lichen planus. A similar
      presentation has not been reported in literature yet, to the best of our
      knowledge. 

PMID- 25386325
TI  - Saree cancer in Indian woman treated successfully with multimodality management.
AB  - Saree is a common, traditional garment of Indian women, wrapped around the waist
      is tightened by a thick cord and with one end draped over the shoulder. Tight
      knot in the same place, sweat, soiling and continuous use can cause pigmentation,
      scaling of the waist and even transform to malignancy. We present here a case of
      saree cancer successfully managed with multimodality therapy. A 50-year-old woman
      was referred to our hospital (India) for itching and non-healing ulcerative
      lesion on waistline. She was wearing saree continuously for 34 years with knot at
      the same place. Magnetic resonance images suggested ulcerative growth with lymph
      node metastasis. She then underwent wide local excision; histopathological
      examination confirmed it was a squamous cell carcinoma. She therefore received
      concomitant chemotherapy and radiotherapy. She is now (2 years after the
      completion of treatment) in remission state. Awareness of saree cancer among
      Indian is important to avoid malignant lesions at waistline. Multimodality
      management with surgery, chemotherapy and radiotherapy is ideal mean for good
      outcome. 

PMID- 25386326
TI  - Delayed diagnosis of adult indolent systemic mastocytosis.
AB  - Systemic mastocytosis (SM) is a rare, heterogeneous disorder characterized by
      infiltration and accumulation of mast cells within multiple organs, most commonly
      the skin. Given the rarity of the disease and the fact that many of its symptoms
      are shared by more common disorders, a diagnosis may be delayed or hindered.
      These patients have an elevated risk of developing potentially life-threatening
      anaphylactoid reactions, thus underscoring the importance of keeping SM in mind
      as a differential diagnosis when a patient presents with chronic, itchy skin
      lesions and a history of multiple allergic reactions to bites, drugs, and
      anesthesia. We present a case illustrating that features of SM common to many
      disorders may hinder or delay its diagnosis. 

PMID- 25386327
TI  - Angina bullosa hemorrhagica: report of 11 cases.
AB  - Angina bullosa hemorrhagica is a rare and benign disorder, usually localized in
      the subepithelial layer of the oral, pharyngeal and esophageal mucosa. The
      lesions are characterized by their sudden onset. They appear as a painless,
      tense, dark red and blood-filled blister in the mouth that rapidly expand and
      rupture spontaneously in 24-48 hours. The underlying etiopathology remains ill
      defined, although it may be a multifactorial phenomenon including diabetes, and
      steroid inhalers. The condition is not attributable to blood dyscrasias, nor
      other vesicular-bullous disorders. In this study, eleven patients with such
      blisters are described. Physical examination of the patients revealed a single
      blister with hemorrhagic content localized in the oral mucosa. Biopsy of the
      lesions showed sub epithelial blisters with a mild infiltrate. In general
      practice, dermatologists could face a blood-filled bullous lesion of the oral
      mucosa. Recognition is, therefore, of great importance for dermatologists. 

PMID- 25386328
TI  - Familial amyloidosis cutis dyschromica in three siblings: report from indonesia.
AB  - Amyloidosis cutis dyschromica (ACD) is an extremely rare type of primary
      cutaneous amyloidosis. To date there are fewer than 40 published cases worldwide;
      some were reported affecting several family members. Its resemblance to other
      common pigmentation disorders makes it rarely recognized at first sight. Our
      patient, the 12-year-old firstborn son of non-consanguineous parents presented
      with generalized mottled pigmentation starting from lower extremities. His
      siblings suffered from similar condition. The clue for diagnosis is the amyloid
      deposition in the papillary dermis. The etiology of ACD is still unknown, but
      genetic factors and ultraviolet radiation are implicated. It is proposed that
      disturbance of keratinocyte repair following ultraviolet radiation results in
      amyloid deposition. The treatment remains a challenge. Oral acitretin treatment,
      thought to repair keratinization defect, gave a slight improvement in our case.
      Our is the first case of ACD reported in Indonesia. 

PMID- 25386329
TI  - Progress in Psoriasis Therapy via Novel Drug Delivery Systems.
AB  - Psoriasis is a lifelong condition which is caused by the negative signals
      produced by immune system, which leads to hyper proliferation and other
      inflammatory reactions on the skin. In this case, keratinocytes which are the
      outermost layer of skin possess shortened life cycle and results in the
      alteration of desquamation process where the cytokines will come out through
      lesions of affected patients and as a result, scaling marks appears on the skin.
      These conditions may negatively affect the patient's quality of life and lead to
      psychosocial stress. Psoriasis can be categorized as mild, moderate and severe
      conditions. Mild psoriasis leads to the formation of rashes, and when it becomes
      moderate, the skin turns into scaly. In severe conditions, red patches may be
      present on skin surface and becomes itchy. Topical therapy continues to be one of
      the pillars for psoriasis management. Drug molecules with target effect on the
      skin tissues and other inflammations should be selected for the treatment of
      psoriasis. Most of the existing drugs lead to systemic intoxication and dryness
      when applied in higher dose. Different scientific approaches for topical delivery
      are being explored by researches including emollient, modified gelling system,
      transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes,
      nano capsules etc. These topical dosage forms are evaluated for various physico
      chemical properties such as drug content, viscosity, pH, extrudability,
      spreadability, toxicity, irritancy, permeability and drug release mechanism. This
      review paper focus attention to the impact of these formulation approaches on
      various anti-psoriasis drugs for their successful treatment. 

PMID- 25386330
TI  - Mucinous eccrine carcinoma of the eyelid: re-emphasizing the need for awareness
      of rare lesions.
AB  - We report here the case of a man presenting with mucinous eccrine carcinoma (MEC)
      involving eyelid. This is a rare adencocarcinoma of the skin that originates from
      the deepest portion of eccrine sweat duct. The aim of our paper is to underline
      the importance of distinguishing MEC from metastatic carcinomas of the skin,
      making clinicians aware that what seems to be a harmless benign lesion may be a
      malignant one. 

PMID- 25386331
TI  - Combined therapeutic use of oral alitretinoin and narrowband ultraviolet-B
      therapy in the treatment of hailey-hailey disease.
AB  - Hailey-Hailey disease (HHD) is a chronic familial bullous disease characterized
      by recurrent blisters and erosions typically at friction-prone areas of the body
      accompanied by acantholysis upon histologic examination. There are a number of
      therapies used in the management of HHD. Its symptoms have been effectively
      treated with antimicrobial therapies, corticosteroids and other agents such as
      cyclosporine and prednisone. However, such treatments are not always effective.
      Therefore, there is a need for new treatments for the management of HHD. In this
      report, a patient with long-standing HHD responsive only to high levels of
      prednisone is described. After the successful tapering and cessation of oral
      prednisone the patient began a new combination therapy of complementary doses of
      oral alitretinoin, and narrowband UVB therapy, which yielded a favorable response
      within 2-3 weeks. After 6 weeks, a mono-therapy of daily (30 mg) oral
      alitretinoin was sufficient to maintain successful near-complete remission of the
      disease. 

PMID- 25386332
TI  - Well Plate Circular Dichroism Reader for the Rapid Determination of Enantiomeric
      Excess.
AB  - Circular dichroism (CD) spectropolarimeters typically employ one photoelastic
      modulator. However, spectropolarimeters employing two or even four modulators are
      more versatile and can be used to subvert common measurement errors arising from
      imperfectly isotropic samples or sample holders. Small linear anisotropies that
      can cause large errors in CD measurement can be associated with multi-well sample
      holders. Thus, high-throughput CD analyses in multi-well plates have not yet been
      demonstrated. One such application is the determination of enantiomeric excess of
      a library of reaction products. Herein, a spectropolarimeter employing four
      photoelastic modulators and a translation stage was used to determine the
      enantiomeric excess of a family of chiral amine complexes much more rapidly than
      could be achieved with a robotic fluid injection system. These experiments are
      proof of concept for high-throughput CD analysis. In practice, commercially
      available glass bottomed well plates are sufficiently strain free such that a
      simple instrument with just one photoelastic modulator and a vertical optical
      train should be able to deliver the CD without special considerations given
      herein. On the other hand, polystyrene well plates cannot be used in this way.

PMID- 25386333
TI  - Top-Down Strategies for the Structural Elucidation of Intact Gram-negative
      Bacterial Endotoxins.
AB  - Re-modelling of lipopolysaccharides, which are the primary constituent of the
      outer cell membrane of Gram-negative bacteria, modulates pathogenesis and
      resistance to microbials. Reported herein is the characterization of intact Gram
      negative bacterial lipooligosaccharides (LOS) via a new strategy utilizing online
      liquid chromatography (LC) coupled with ultraviolet photodissociation (UVPD) mass
      spectrometry. Compared to collision-based MS/MS methods, UVPD and UVPD/HCD
      promoted a greater array of cleavages within both the glycan and lipid moieties,
      including C-C, C-N, C-O cleavages in the acyl chains as well as glycosidic and
      cross-ring cleavages, thus providing the most far-reaching structural
      characterization of LOS. This LC-MS/MS strategy affords a robust analytical
      method to structurally characterize complex mixtures of bacterial endotoxins that
      maintains the integrity of the core oligosaccharide and lipid A domains of LOS,
      providing direct feedback about the cell envelope architectures and LOS
      modification strategies involved in resistance host innate immune defense.

PMID- 25386334
TI  - Natalamycin A, an Ansamycin from a Termite-Associated Streptomyces sp.
AB  - We report a preliminary functional and complete structural characterization of a
      highly unusual geldanamycin analog, natalamycin A, that was isolated from
      Streptomyces strain M56 recovered from a South African nest of Macrotermes
      natalensis termites. Bioassay-guided fractionation based on antifungal activity
      led to the isolation of natalamycin A, and a combination of NMR spectroscopy and
      X-ray crystallographic analysis, including highly-accurate quantum-chemical NMR
      calculations on the largest and most conformationally-flexible system to date,
      revealed natalamycin A's three-dimensional solid- and solution-state structure.
      This structure along with the structures of related compounds isolated from the
      same source suggest a geldanamycin-like biosynthetic pathway with unusual post
      PKS modifications.

PMID- 25386335
TI  - Function-Oriented Investigations of a Peptide-Based Catalyst that Mediates
      Enantioselective Allylic Alcohol Epoxidation.
AB  - We detail an investigation of a peptide-based catalyst 6 that is effective for
      the site- (>100:1:1) and enantioselective epoxidation (86% ee) of farnesol.
      Studies of the substrate scope exhibited by the catalyst are included, along with
      an exploration of optimized reaction conditions. Mechanistic studies are
      reported, including relative rate determinations for the catalyst and propionic
      acid, a historical perspective, truncation studies, and modeling using NMR data.
      Our compiled data advances our understanding of the inner workings of a catalyst
      that was identified through combinatorial means.

PMID- 25386336
TI  - Hemolytic venoms from marine cnidarian jellyfish - an overview.
AB  - Cnidarian jellyfish are viewed as an emergent problem in several coastal zones
      throughout the world. Recurrent outbreaks pose a serious threat to tourists and
      bathers, as well as to sea-workers, involving health and economical aspects. As a
      rule, cnidarian stinging as a consequence of nematocyst firing induces merely
      local symptoms but cardiovascular or neurological complications can also occur.
      Hemolysis is a frequent effect of cnidarian stinging; this dangerous condition is
      known to be caused by several venoms and can sometimes be lethal. At present, the
      bulk of data concerning hemolytic cnidarian venoms comes from the study of
      benthic species, such as sea anemones and soft corals, but hemolytic factors were
      found in venoms of several siphonophore, cubozoan and scyphozoan jellyfish, which
      are mainly involved in the envenomation of bathers and sea-workers. Therefore,
      the aim of this paper is to review the scientific literature concerning the
      hemolytic venoms from cnidarian jellyfish taking into consideration their
      importance in human pathology as well as health implications and possible
      therapeutic measures. 

PMID- 25386337
TI  - DNA-Based Asymmetric Catalysis: Role of Ionic Solvents and Glymes.
AB  - Recently, DNA has been evaluated as a chiral scaffold for metal complexes to
      construct so called 'DNA-based hybrid catalysts', a robust and inexpensive
      alternative to enzymes. The unique chiral structure of DNA allows the hybrid
      catalysts to catalyze various asymmetric synthesis reactions. However, most
      current studies used aqueous buffers as solvents for these asymmetric reactions,
      where substrates/products are typically suspended in the solutions. The mass
      transfer limitation usually requires a long reaction time. To overcome this
      hurdle and to advance DNA-based asymmetric catalysis, we evaluated a series of
      ionic liquids (ILs), inorganic salts, deep eutectic solvents (DES), glymes,
      glycols, acetonitrile and methanol as co-solvents/additives for the DNA-based
      asymmetric Michael addition. In general, these additives induce indistinguishable
      changes to the DNA B-form duplex conformation as suggested by circular dichroism
      (CD) spectroscopy, but impose a significant influence on the catalytic efficiency
      of the DNA-based hybrid catalyst. Conventional organic solvents (e.g.
      acetonitrile and methanol) led to poor product yields and/or low
      enantioselectivities. Most ILs and inorganic salts cause the deactivation of the
      hybrid catalyst except 0.2 M [BMIM][CF3COO] (95.4% ee and 93% yield) and 0.2 M
      [BMIM]Cl (93.7% ee and 89% yield). Several other additives have also been found
      to improve the catalytic efficiency of the DNA-based hybrid catalyst (control
      reaction without additive gives >99% ee and 87% yield): 0.4 M glycerol (>99% ee
      and 96% yield at 5  degrees C or 96.2% ee and 83% yield at room temperature), 0.2
      M choline chloride/glycerol (1:2) (92.4% ee and 90% yield at 5  degrees C or
      94.0% ee and 88% yield at room temperature), and 0.5 M dipropylene glycol
      dimethyl ether (>99% ee and 87% yield at room temperature). The use of some co
      solvents/additives allows the Michael addition to be performed at a higher
      temperature (e.g. room temperature vs 5  degrees C) and a shorter reaction time
      (24 h vs 3 days). In addition, we found that a brief pre-sonication (5 min) of
      DNA in MOPS buffer prior to the reaction could improve the performance of the DNA
      based hybrid catalyst. We have also shown that this DNA-based catalysis method is
      suitable for a variety of different substrates and relatively large-scale
      reactions. In conclusion, a judicious selection of benign co-solvents/additives
      could improve the catalytic efficiency of DNA-based hybrid catalyst.

PMID- 25386338
TI  - A reference bacterial genome dataset generated on the MinIONTM portable single
      molecule nanopore sequencer.
AB  - BACKGROUND: The MinIONTM is a new, portable single-molecule sequencer developed
      by Oxford Nanopore Technologies. It measures four inches in length and is powered
      from the USB 3.0 port of a laptop computer. The MinIONTM measures the change in
      current resulting from DNA strands interacting with a charged protein nanopore.
      These measurements can then be used to deduce the underlying nucleotide sequence.
      FINDINGS: We present a read dataset from whole-genome shotgun sequencing of the
      model organism Escherichia coli K-12 substr. MG1655 generated on a MinIONTM
      device during the early-access MinIONTM Access Program (MAP). Sequencing runs of
      the MinIONTM are presented, one generated using R7 chemistry (released in July
      2014) and one using R7.3 (released in September 2014). CONCLUSIONS: Base-called
      sequence data are provided to demonstrate the nature of data produced by the
      MinIONTM platform and to encourage the development of customised methods for
      alignment, consensus and variant calling, de novo assembly and scaffolding. FAST5
      files containing event data within the HDF5 container format are provided to
      assist with the development of improved base-calling methods.

PMID- 25386339
TI  - Biomaterial arrays with defined adhesion ligand densities and matrix stiffness
      identify distinct phenotypes for tumorigenic and nontumorigenic human mesenchymal
      cell types.
AB  - Here, we aimed to investigate migration of a model tumor cell line (HT-1080
      fibrosarcoma cells, HT-1080s) using synthetic biomaterials to systematically vary
      peptide ligand density and substrate stiffness. A range of substrate elastic
      moduli were investigated by using poly(ethylene glycol) (PEG) hydrogel arrays
      (0.34 - 17 kPa) and self-assembled monolayer (SAM) arrays (~0.1-1 GPa), while
      cell adhesion was tuned by varying the presentation of Arg-Gly-Asp (RGD)
      containing peptides. HT-1080 motility was insensitive to cell adhesion ligand
      density on RGD-SAMs, as they migrated with similar speed and directionality for a
      wide range of RGD densities (0.2-5% mol fraction RGD). Similarly, HT-1080
      migration speed was weakly dependent on adhesion on 0.34 kPa PEG surfaces. On 13
      kPa surfaces, a sharp initial increase in cell speed was observed at low RGD
      concentration, with no further changes observed as RGD concentration was
      increased further. An increase in cell speed ~ two-fold for the 13 kPa relative
      to the 0.34 kPa PEG surface suggested an important role for substrate stiffness
      in mediating motility, which was confirmed for HT-1080s migrating on variable
      modulus PEG hydrogels with constant RGD concentration. Notably, despite ~ two
      fold changes in cell speed over a wide range of moduli, HT-1080s adopted rounded
      morphologies on all surfaces investigated, which contrasted with well spread
      primary human mesenchymal stem cells (hMSCs). Taken together, our results
      demonstrate that HT-1080s are morphologically distinct from primary mesenchymal
      cells (hMSCs) and migrate with minimal dependence on cell adhesion for surfaces
      within a wide range of moduli, whereas motility is strongly influenced by matrix
      mechanical properties.

PMID- 25386340
TI  - Dendritic cell cancer vaccines: from the bench to the bedside.
AB  - The recognition that the development of cancer is associated with acquired
      immunodeficiency, mostly against cancer cells themselves, and understanding
      pathways inducing this immunosuppression, has led to a tremendous development of
      new immunological approaches, both vaccines and drugs, which overcome this
      inhibition. Both "passive" (e.g. strategies relying on the administration of
      specific T cells) and "active" vaccines (e.g. peptide-directed or whole-cell
      vaccines) have become attractive immunological approaches, inducing cell death by
      targeting tumor-associated antigens. Whereas peptide-targeted vaccines are
      usually directed against a single antigen, whole-cell vaccines (e.g. dendritic
      cell vaccines) are aimed to induce robust responsiveness by targeting several
      tumor-related antigens simultaneously. The combination of vaccines with new
      immuno-stimulating agents which target "immunosuppressive checkpoints" (anti-CTLA
      4, PD-1, etc.) is likely to improve and maintain immune response induced by
      vaccination. 

PMID- 25386341
TI  - Genetic stratification in myeloid diseases: from risk assessment to clinical
      decision support tool.
AB  - Genetic aberrations have become a dominant factor in the stratification of
      myeloid malignancies. Cytogenetic and a few mutation studies are the backbone of
      risk assessment models of myeloid malignancies which are a major consideration in
      clinical decisions, especially patient assignment for allogeneic stem cell
      transplantation. Progress in our understanding of the genetic basis of the
      pathogenesis of myeloid malignancies and the growing capabilities of mass
      sequencing may add new roles for the clinical usage of genetic data. A few
      recently identified mutations recognized to be associated with specific diseases
      or clinical scenarios may soon become part of the diagnostic criteria of such
      conditions. Mutational studies may also advance our capabilities for a more
      efficient patient selection process, assigning the most effective therapy at the
      best timing for each patient. The clinical utility of genetic data is anticipated
      to advance further with the adoption of deep sequencing and next-generation
      sequencing techniques. We herein suggest some future potential applications of
      sequential genetic data to identify pending deteriorations at time points which
      are the best for aggressive interventions such as allogeneic stem cell
      transplantation. Genetics is moving from being mostly a prognostic factor to
      becoming a multitasking decision support tool for hematologists. Physicians must
      pay attention to advances in molecular hematology as it will soon be accessible
      and influential for most of our patients. 

PMID- 25386342
TI  - ADAMTS-13 in the Diagnosis and Management of Thrombotic Microangiopathies.
AB  - Thrombotic microangiopathies (TMAs) comprise a group of distinct disorders
      characterized by microangiopathic hemolytic anemia, thrombocytopenia, and
      microvascular thrombosis. For many years distinction between these TMAs,
      especially between thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic
      syndrome (HUS), remained purely clinical and hard to make. Recent discoveries
      shed light on different pathogenesis of TTP and HUS. Ultra-large von Willebrand
      factor (UL-VWF) platelet thrombi, resulting from the deficiency of cleavage
      protease which is now known as ADAMTS-13 (a disintegrin and metalloproteinase
      with a thrombospondin type 1 motif, member 13), were found to cause TTP
      pathology, while Shiga toxins or abnormalities in regulation of the complement
      system cause microangiopathy and thrombosis in HUS. TMAs may appear in various
      conditions such as pregnancy, inflammation, malignancy, or exposure to drugs.
      These conditions might cause acquired TTP, HUS, or other TMAs, or might be a
      trigger in individuals with genetic predisposition to ADAMTS-13 or complement
      factor H deficiency. Differentiation between these TMAs is highly important for
      urgent initiation of appropriate therapy. Measurement of ADAMTS-13 activity and
      anti-ADAMTS-13 antibody levels may advance this differentiation resulting in
      accurate diagnosis. Additionally, assessment of ADAMTS-13 levels can be a tool
      for monitoring treatment efficacy and relapse risk, allowing consideration of
      therapy addition or change. In the past few years, great improvements in ADAMTS
      13 assays have been made, and tests with increased sensitivity, specificity,
      reproducibility, and shorter turnaround time are now available. These new assays
      enable ADAMTS-13 measurement in routine clinical diagnostic laboratories, which
      may ultimately result in improvement of TMA management. 

PMID- 25386343
TI  - Minimal residual disease surveillance in chronic lymphocytic leukemia by
      fluorescence-activated cell sorting.
AB  - Achievement of complete response (CR) to therapy in chronic lymphocytic leukemia
      (CLL) has become a feasible goal, directly correlating with prolonged survival.
      It has been established that the classic definition of CR actually encompasses a
      variety of disease loads, and more sensitive multiparameter flow cytometry and
      polymerase chain reaction methods can detect the disease burden with a much
      higher sensitivity. Detection of malignant cells with a sensitivity of 1 tumor
      cell in 10,000 cells (10(-4)), using the abovementioned sophisticated techniques,
      is the current cutoff for minimal residual disease (MRD). Tumor burdens lower
      than 10(-4) are defined as MRD-negative. Several studies in CLL have determined
      the achievement of MRD negativity as an independent favorable prognostic factor,
      leading to prolonged disease-free and overall survival, regardless of the
      treatment protocol or the presence of other pre-existing prognostic indicators.
      Minimal residual disease evaluation using flow cytometry is a sensitive and
      applicable approach which is expected to become an integral part of future
      prospective trials in CLL designed to assess the role of MRD surveillance in
      treatment tailoring. 

PMID- 25386344
TI  - Hematopoietic stem cell transplantation-50 years of evolution and future
      perspectives.
AB  - Hematopoietic stem cell transplantation is a highly specialized and unique
      medical procedure. Autologous transplantation allows the administration of high
      dose chemotherapy without prolonged bone marrow aplasia. In allogeneic
      transplantation, donor-derived stem cells provide alloimmunity that enables a
      graft-versus-tumor effect to eradicate residual disease and prevent relapse. The
      first allogeneic transplantation was performed by E. Donnall Thomas in 1957.
      Since then the field has evolved and expanded worldwide. New indications beside
      acute leukemia and aplastic anemia have been constantly explored and now include
      congenital disorders of the hematopoietic system, metabolic disorders, and
      autoimmune disease. The use of matched unrelated donors, umbilical cord blood
      units, and partially matched related donors has dramatically extended the
      availability of allogeneic transplantation. Transplant-related mortality has
      decreased due to improved supportive care, including better strategies to prevent
      severe infections and with the incorporation of reduced-intensity conditioning
      protocols that lowered the toxicity and allowed for transplantation in older
      patients. However, disease relapse and graft-versus-host disease remain the two
      major causes of mortality with unsatisfactory progress. Intense research aiming
      to improve adoptive immunotherapy and increase graft-versus-leukemia response
      while decreasing graft-versus-host response might bring the next breakthrough in
      allogeneic transplantation. Strategies of graft manipulation, tumor-associated
      antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy
      have already proved clinically efficient. In the following years, allogeneic
      transplantation is likely to become more complex, more individualized, and more
      efficient. 

PMID- 25386345
TI  - Hodgkin disease-an ever-evolving therapy.
AB  - Therapy of Hodgkin lymphoma (HL) is a rapidly changing field due to plenty of
      currently emerging data. Treatment approaches are currently based on tailoring of
      therapy in order to achieve a maximal response with minimal toxicity. Since the
      median age of HL patients is 33 years and their prospective life expectancy of
      another half a century, a major emphasis needs to be put on dramatic reduction of
      later toxicity. The assessment of the treatment effect should be based not only
      on progression-free survival, but should include evaluation of cardiac toxicity,
      secondary neoplasms, and fertility in the long-term follow-up. The ancient
      principle "first do no harm" should be central in HL therapy. Completion of
      ongoing and currently initiated trials could elucidate multiple issues related to
      the management of HL patients. 

PMID- 25386346
TI  - Brain neoplasms and coagulation-lessons from heterogeneity.
AB  - The coagulation system constitutes an important facet of the unique vascular
      microenvironment in which primary and metastatic brain tumors evolve and
      progress. While brain tumor cells express tissue factor (TF) and other effectors
      of the coagulation system (coagulome), their propensity to induce local and
      peripheral thrombosis is highly diverse, most dramatic in the case of
      glioblastoma multiforme (GBM), and less obvious in pediatric tumors. While the
      immediate medical needs often frame the discussion on current clinical
      challenges, the coagulation pathway may contribute to brain tumor progression
      through subtle, context-dependent, and non-coagulant effects, such as induction
      of inflammation, angiogenesis, or by responding to iatrogenic insults (e.g.
      surgery). In this regard, the emerging molecular diversity of brain tumor
      suptypes (e.g. in glioma and medulloblastoma) highlights the link between
      oncogenic pathways and the tumor repertoire of coagulation system regulators
      (coagulome). This relationship may influence the mechanisms of spontaneous and
      therapeutically provoked tumor cell interactions with the coagulation system as a
      whole. Indeed, oncogenes (EGFR, MET) and tumor suppressors (PTEN, TP53) may alter
      the expression, activity, and vesicular release of tissue factor (TF), and cause
      other changes. Conversely, the coagulant microenvironment may also influence the
      molecular evolution of brain tumor cells through selective and instructive cues.
      We suggest that effective targeting of the coagulation system in brain tumors
      should be explored through molecular stratification, stage-specific analysis, and
      more personalized approaches including thromboprophylaxis and adjuvant treatment
      aimed at improvement of patient survival. 

PMID- 25386347
TI  - Heparanase and coagulation-new insights.
AB  - Heparanase, a beta-D-endoglucuronidase abundant in platelets that was discovered
      30 years ago, is an enzyme that cleaves heparan sulfate side chains on the cell
      surface and in the extracellular matrix. It was later recognized as being a pro
      inflammatory and pro-metastatic protein. We had earlier demonstrated that
      heparanase may also affect the hemostatic system in a non-enzymatic manner. We
      had shown that heparanase up-regulated the expression of the blood coagulation
      initiator tissue factor (TF) and interacted with the tissue factor pathway
      inhibitor (TFPI) on the cell surface membrane of endothelial and tumor cells,
      leading to dissociation of TFPI and resulting in increased cell surface
      coagulation activity. Moreover, we have demonstrated that heparanase directly
      enhanced TF activity which led to increased factor Xa production and subsequent
      activation of the coagulation system. Recently, heparanase inhibitory peptides
      derived of TFPI-2 were demonstrated by us to inhibit heparanase procoagulant
      activity and attenuate sepsis in mouse models. 

PMID- 25386348
TI  - Extracellular vesicles in hematological disorders.
AB  - Extracellular vesicles (EVs), comprised of exosomes, microparticles, apoptotic
      bodies, and other microvesicles, are shed from a variety of cells upon cell
      activation or apoptosis. EVs promote clot formation, mediate pro-inflammatory
      processes, transfer proteins and miRNA to cells, and induce cell signaling that
      regulates cell differentiation, proliferation, migration, invasion, and
      apoptosis. This paper will review the contribution of EVs in hematological
      disorders, including hemoglobinopathies (sickle cell disease, thalassemia),
      paroxysmal nocturnal hemoglobinuria, and hematological malignancies (lymphomas,
      myelomas, and acute and chronic leukemias). 

PMID- 25386350
TI  - Coagulation and placenta-mediated complications.
AB  - Pregnancy is a physiological hypercoagulable state, preparing the mother for the
      hemostatic challenge of delivery. However, this is associated with an increased
      risk of venous thrombosis and placenta-mediated complications, which present
      major challenges for mother and fetus. Although these conditions are
      heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has
      been associated with recurrent pregnancy loss and gestational vascular
      complications, such as early-onset pre-eclampsia and placental abruption.
      Prevention of such placenta-mediated complications, which collectively complicate
      up to 15% of pregnancies, is a major issue for women's health. Prospective
      interventional studies stratified by current knowledge of pathophysiological
      mechanisms related to placental and systemic hemostatic alterations will impact
      on the management of pregnancies at risk of these complications. 

PMID- 25386349
TI  - Signal, transduction, and the hematopoietic stem cell.
AB  - The hematopoietic stem cell (HSC) is a unique cell positioned highest in the
      hematopoietic hierarchical system. The HSC has the ability to stay in quiescence,
      to self-renew, or to differentiate and generate all lineages of blood cells. The
      path to be actualized is influenced by signals that derive from the cell's
      microenvironment, which activate molecular pathways inside the cell. Signaling
      pathways are commonly organized through inducible protein-protein interactions,
      mediated by adaptor proteins that link activated receptors to cytoplasmic
      effectors. This review will focus on the signaling molecules and how they work in
      concert to determine the HSC's fate. 

PMID- 25386351
TI  - Calreticulin mutations in myeloproliferative neoplasms.
AB  - With the discovery of the JAK2V617F mutation in patients with Philadelphia
      chromosome-negative (Ph(-)) myeloproliferative neoplasms (MPNs) in 2005, major
      advances have been made in the diagnosis of MPNs, in understanding of their
      pathogenesis involving the JAK/STAT pathway, and finally in the development of
      novel therapies targeting this pathway. Nevertheless, it remains unknown which
      mutations exist in approximately one-third of patients with non-mutated JAK2 or
      MPL essential thrombocythemia (ET) and primary myelofibrosis (PMF). At the end of
      2013, two studies identified recurrent mutations in the gene encoding
      calreticulin (CALR) using whole-exome sequencing. These mutations were revealed
      in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in
      polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations) and
      recurrent 5-bp insertions (type 2 mutations) in exon 9 of the CALR gene (the last
      exon encoding the C-terminal amino acids of the protein calreticulin) were
      detected and found always to generate frameshift mutations. All detected mutant
      calreticulin proteins shared a novel amino acid sequence at the C-terminal.
      Mutations in CALR are acquired early in the clonal history of the disease, and
      they cause activation of JAK/STAT signaling. The CALR mutations are the second
      most frequent mutations in Ph(-) MPN patients after the JAK2V617F mutation, and
      their detection has significantly improved the diagnostic approach for ET and
      PMF. The characteristics of the CALR mutations as well as their diagnostic,
      clinical, and pathogenesis implications are discussed in this review. 

PMID- 25386352
TI  - Coagulation and mental disorders.
AB  - The neurovascular unit is a key player in brain development, homeostasis, and
      pathology. Mental stress affects coagulation, while severe mental illnesses, such
      as recurrent depression and schizophrenia, are associated with an increased
      thrombotic risk and cardiovascular morbidity. Evidence indicates that the
      hemostatic system is involved to some extent in the pathogenesis, morbidity, and
      prognosis of a wide variety of psychiatric disorders. The current review focuses
      on emerging data linking coagulation and some psychiatric disorders. 

PMID- 25386353
TI  - VTE Registry: What Can Be Learned from RIETE?
AB  - The Registro Informatizado de Enfermedad TromboEmbolica (RIETE Registry) is an
      ongoing, international, prospective registry of consecutive patients with acute
      venous thromboembolism (VTE) designed to gather and analyze data on treatment
      patterns and outcomes in patients with acute VTE. It started in Spain in 2001,
      and 6 years later the database was translated into English with the aim to expand
      the Registry to other countries. In contrast to randomized controlled trials,
      there is no imposed experimental intervention: the management is determined
      solely by physicians. Thus, it provides data on patients with VTE in a real-world
      situation with an unselected patient population. Data from RIETE are hypothesis
      generating and provide feedback from real-world clinical situations. So far, we
      learned about the natural history of VTE in patients with relative or absolute
      contraindications to anticoagulant therapy. We also learned interesting aspects
      on the natural history of VTE, and we built a number of prognostic scores to
      identify VTE patients at low, moderate, or high risk for adverse outcome. 

PMID- 25386354
TI  - Does gender matter in non-hodgkin lymphoma? Differences in epidemiology, clinical
      behavior, and therapy.
AB  - Non-Hodgkin lymphoma (NHL) is one of the most common hematologic malignancies
      worldwide. The incidence of NHL has been rising for several decades; however, in
      the last 20 years, it reached a plateau. NHL incidence among males is
      significantly higher than in females. In addition to gender itself, gravidity has
      a protective role against NHL occurrence. Gender also matters in terms of NHL
      clinical characteristics. For example, female predominance was found in three
      extra-nodal sites (the breast, thyroid, and the respiratory system) occasionally
      involved in NHL. The diagnosis of NHL during pregnancy is associated with a
      unique clinical behavior. It is usually diagnosed in the second or third
      trimester and in advanced stage. Furthermore, the histological subtype is highly
      aggressive, and reproductive organ involvement is common. The reduced rate of NHL
      among females may be explained by direct effects of estrogens on lymphoma cell
      proliferation or by its effect on anti-tumor immune response. Gender has an
      important role in responsiveness to standard B cell NHL treatment. Among older
      adults, women benefited more from the addition of the anti-CD20 antibody
      rituximab to standard chemotherapy regimens. This phenomenon can be explained by
      the difference in clearance rate of rituximab that was found to be significantly
      lower among older females than older males. In mantle cell lymphoma, women
      receiving lenalidomide have higher rates of response. An understanding of the
      mechanisms responsible for gender-associated NHL differences will ultimately
      improve the clinical approach, allowing for a more accurate assessment of
      prognosis and patient-tailored treatment. 

PMID- 25386355
TI  - Hemorrhagic aspects of Gaucher disease.
AB  - Gaucher disease (GD) is an inherited lysosomal disorder, originating from
      deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Normally,
      GCase hydrolyzes glucocerebroside (GC) to glucose and ceramide; however, impaired
      activity of this enzyme leads to the accumulation of GC in macrophages, termed
      "Gaucher cells." Gaucher disease is associated with hepatosplenomegaly,
      cytopenias, skeletal complications and in some forms involves the central nervous
      system. Coagulation abnormalities are common among GD patients due to impaired
      production and chronic consumption of coagulation factors. Bleeding phenomena are
      variable (as are other symptoms of GD) and include mucosal and surgical
      hemorrhages. FOUR MAIN ETIOLOGICAL FACTORS ACCOUNT FOR THE HEMOSTATIC DEFECT IN
      GD: thrombocytopenia, abnormal platelet function, reduced production of
      coagulation factors, and activation of fibrinolysis. Thrombocytopenia relates not
      only to hypersplenism and decreased megakaryopoiesis by the infiltrated bone
      marrow but also to immune thrombocytopenia. Autoimmunity, especially the
      induction of platelet antibody production, might cause persistent
      thrombocytopenia. Enzyme replacement therapy reverses only part of the impaired
      coagulation system in Gaucher disease. Other therapeutic and supportive measures
      should be considered to prevent and/or treat bleeding in GD. Gaucher patients
      should be evaluated routinely for coagulation abnormalities especially prior to
      surgery and dental and obstetric procedures. 

PMID- 25386356
TI  - Risk-adapted management of acute pulmonary embolism: recent evidence, new
      guidelines.
AB  - Venous thromboembolism (VTE), the third most frequent acute cardiovascular
      syndrome, may cause life-threatening complications and imposes a substantial
      socio-economic burden. During the past years, several landmark trials paved the
      way towards novel strategies in acute and long-term management of patients with
      acute pulmonary embolism (PE). Risk stratification is increasingly recognized as
      a cornerstone for an adequate diagnostic and therapeutic management of the highly
      heterogeneous population of patients with acute PE. Recently published European
      Guidelines emphasize the importance of clinical prediction rules in combination
      with imaging procedures (assessment of right ventricular function) and laboratory
      biomarkers (indicative of myocardial stress or injury) for identification of
      normotensive PE patients at intermediate risk for an adverse short-term outcome.
      In this patient group, systemic full-dose thrombolysis was associated with a
      significantly increased risk of intracranial bleeding, a complication which
      discourages its clinical application unless hemodynamic decompensation occurs. A
      large-scale clinical trial program evaluating new oral anticoagulants in the
      initial and long-term treatment of venous thromboembolism showed at least
      comparable efficacy and presumably increased safety of these drugs compared to
      the current standard treatment. Research is continuing on catheter-directed,
      ultrasound-assisted, local, low-dose thrombolysis in the management of
      intermediate-risk PE. 

PMID- 25386357
TI  - Implementing thrombosis guidelines in cancer patients: a review.
AB  - Venous thromboembolism is a frequent and serious complication in patients with
      cancer. It is an independent prognostic factor of death in cancer patients and
      the second leading cause of death, but physicians often underestimate its
      importance, as well as the need for adequate prevention and treatment. Management
      of venous thromboembolism in patients with cancer requires the coordinated
      efforts of a wide range of clinicians, highlighting the importance of a
      multidisciplinary approach. However, a lack of consensus among various national
      and international clinical practice guidelines has contributed to knowledge and
      practice gaps among practitioners, and inconsistent approaches to venous
      thromboembolism. The 2013 international guidelines for thrombosis in cancer have
      sought to address these gaps by critically re-evaluating the evidence coming from
      clinical trials and synthesizing a number of guidelines documents. An
      individualized approach to prophylaxis is recommended for all patients. 

PMID- 25386358
TI  - Effectiveness of counseling provided by primary care doctors and nurses in
      increasing glaucoma screening rates.
AB  - Introduction. An effective screening that can prevent glaucoma-related blindness
      largely depends on successful recruitment. This study was to assess the
      effectiveness of one-on-one counseling carried out by primary care doctors and
      nurses to increase glaucoma screening rates. Material and Methods. The study,
      carried out in an urban primary care center, involved 308 persons aged 35-87
      years who were assigned to a doctor's, nurse's, or control group (N = 109, 110,
      and 89, resp.). Interventions by doctors and nurses included a brief one-on-one
      counseling session, while only a screening history was taken from controls. The
      number of people in each group with a positive screening status was assessed by
      telephone interview three months after the visit. Results. The percentage of
      persons in the nurse's counseling group who claimed being subjected to screening
      was more than four times higher than in the control group (20.9% versus 4.5%, P =
      0.002). The doctor's interventions resulted in almost a tripled screening rate as
      compared to the control group (12.8% versus 4.5%, P = 0.052). There was no
      significant difference between screening rates in doctor's and nurse's groups (P
      = 0.212). Conclusions. In the studied population, counseling provided by nurses
      proved to be an efficacious method to encourage patients to undergo glaucoma
      screening. 

PMID- 25386359
TI  - Prevalence of and risk factors for dry eye symptom in mainland china: a
      systematic review and meta-analysis.
AB  - Purpose. To evaluate the pooled prevalence rate and risk factors of dry eye
      symptoms (DES) in mainland China. Methods. All the published population-based
      studies investigating the prevalence of DES in China were searched and evaluated
      against inclusion criteria. A systematic review and meta-analysis were performed.
      Results. Twelve out of the 119 identified studies were included in the meta
      analysis. The pooled prevalence of DES in China was 17.0%. Female individuals,
      subjects living in the Northern and Western China, and over 60 years of age had
      significantly higher prevalent rates (21.6%, 17.9%, 31.3%, and 34.4%, resp.)
      compared with their counterparts. Patients with diabetes were also found to be
      more vulnerable to DES. Conclusions. The pooled prevalence rate of DES in
      mainland China was lower than that in other Asian regions and countries. A
      remarkable discrepancy in the prevalence in different geographic regions was
      noted. Aging, female gender, and diabetes were found to be risk factors for DES
      in China. 

PMID- 25386360
TI  - Rethinking obesity counseling: having the French Fry Discussion.
AB  - Childhood obesity is a complex problem that warrants early intervention. General
      recommendations for obesity prevention and nutrition counseling exist. However,
      these are notably imprecise with regard to early and targeted interventions to
      prevent and treat obesity in pediatric populations. This study examines family
      medicine primary care providers' (PCPs) perceived barriers for preventing and
      treating pediatric obesity and their related practice behavior during well-child
      visits. METHODS: A written survey addressing perceived barriers and current
      practices addressing obesity at well-child visits were administered to PCPs at
      eleven family medicine clinics in the Duke University Health System. RESULTS: The
      most common perceived barriers identified by PCPs to prevention or treatment of
      obesity in children were families not getting enough exercise (93%) and families
      too often having fast food meals (86%). Most PCPs do not discuss fast foods at or
      prior to the twelve-month well-child visit. The two-year visit is the first well
      child visit at which a majority of PCPs (68%) discuss fast food. CONCLUSION: No
      clear consensus exists as to when PCPs should discuss fast food in early well
      child checks. Previous research has shown a profound shift in children's dietary
      habits toward fast foods, such as French fries, that occurs between the one- and
      two-year well-child checks. Consideration should be given to having a "French Fry
      Discussion" at every twelve-month well-child care visit.

PMID- 25386361
TI  - Synthesis and Anticancer Properties of Silver(I) Complexes Containing 2,6
      Bis(substituted)pyridine Derivatives.
AB  - Several new 2,6-bis(substituted)pyridine ligands and 2,6-bis(substituted)pyridine
      Ag(I) nitrate complexes were synthesized and characterized spectroscopically. The
      newly synthesized ligands include pyridine-2,6-bis(3-oxopropanenitrile) (1),
      pyridine-2,6-bis(2-cyano-N-phenyl-3-oxopropanethioamide) (2), and pyridine-2,6
      bis((E)-2-(2-phenylhydrazono)-3-oxopropanenitrile) (3). The newly synthesized
      ligands and silver(I) complexes were evaluated for their in vitro anticancer
      activity against four human cancer cell lines including hepatocellular carcinoma
      (HePG2), lung adenocarcinoma (A549), colon carcinoma (HT29), and breast
      adenocarcinoma (MCF7). Most of the newly synthesized silver(I) complexes
      exhibited better activity than the ligands, and the results have been compared
      with doxorubicin as a reference drug. 

PMID- 25386363
TI  - Geospatial Relationships between Awareness and Utilization of Community Exercise
      Resources and Physical Activity Levels in Older Adults.
AB  - Introduction. It is unclear if community-based fitness resources (CBFR) translate
      to heightened activity levels within neighboring areas. The purpose of this study
      was to determine whether awareness and utilization of fitness resources and
      physical activity differed depending on residential distance from CBFR. Methods.
      Four hundred and seventeen older adults (72.9 +/- 7.7 years) were randomly
      recruited from three spatial tiers (<=1.6, >1.6 to <=3.2, and >3.2 to 8.0 km)
      surrounding seven senior centers, which housed CBFR. Participants completed
      questionnaires on health history, CBFR, and physical activity, gathering data on
      CBFR awareness, utilization, and barriers, overall levels, and predictors to
      engagement in moderate to vigorous physical activity (MVPA). Results. Across
      spatial tiers, there were no differences in positive awareness rates of CBFR or
      CBFR utilization. Engagement in MVPA differed across spatial tiers (P < 0.001),
      with the >3.2 to 8.0 km radius having the highest mean energy expenditure. Across
      all sites, age and income level (P < 0.05) were significant predictors of low and
      high amounts of MVPA, respectively, and current health status and lack of
      interest represented barriers to CBFR utilization (P < 0.05). Conclusion. Closer
      proximity to CBFR did not impact awareness or utilization rates and had an
      inverse relationship with physical activity. 

PMID- 25386362
TI  - MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity.
AB  - As a crucial component of DNA replication licensing system, minichromosome
      maintenance (MCM) 2-7 complex acts as the eukaryotic DNA replicative helicase.
      The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and
      Cdt1 to form the prereplication complex. Although the MCMs are well known as
      replicative helicases, their overabundance and distribution patterns on chromatin
      present a paradox called the "MCM paradox." Several approaches had been taken to
      solve the MCM paradox and describe the purpose of excess MCMs distributed beyond
      the replication origins. Alternative functions of these MCMs rather than a
      helicase had also been proposed. This review focuses on several models and
      concepts generated to solve the MCM paradox coinciding with their helicase
      function and provides insight into the concept that excess MCMs are meant for
      licensing dormant origins as a backup during replication stress. Finally, we
      extend our view towards the effect of alteration of MCM level. Though an excess
      MCM constituent is needed for normal cells to withstand stress, there must be a
      delineation of the threshold level in normal and malignant cells. This review
      also outlooks the future prospects to better understand the MCM biology. 

PMID- 25386364
TI  - Usefulness of lipid apheresis in the treatment of familial hypercholesterolemia.
AB  - Lipid apheresis is used to treat patients with severe hyperlipidemia by reducing
      low-density lipoprotein cholesterol (LDL-C). This study examines the effect of
      apheresis on the lipid panel and cardiac event rates before and after apheresis.
      An electronic health record screen of ambulatory patients identified 11 active
      patients undergoing lipid apheresis with 10/11 carrying a diagnosis of FH.
      Baseline demographics, pre- and postapheresis lipid levels, highest recorded LDL
      C, cardiac events, current medications, and first apheresis treatment were
      recorded. Patients completed a questionnaire and self-reported risk factors and
      interest in alternative treatment. There were significant reductions in mean
      total cholesterol (-58.4%), LDL-C (-71.9%), triglycerides (-51%), high-density
      lipoprotein (HDL) cholesterol (-9.3%), and non-HDL (-68.2%) values. Thirty-four
      cardiac events were documented in 8 patients before apheresis, compared with 9
      events in 5 patients after apheresis. Our survey showed a high prevalence of
      statin intolerance (64%), with the majority (90%) of participants indicating an
      interest in alternative treatment options. Our results have shown that lipid
      apheresis primary effect is a marked reduction in LDL-C cholesterol levels and
      may reduce the recurrence of cardiac events. Apheresis should be compared to the
      newer alternative treatment modalities in a randomized fashion due to patient
      interest in alternative options. 

PMID- 25386365
TI  - Prevalence of Acute Symptoms among Workers in Printing Factories.
AB  - Objective. To identify socioeconomic situation factors and behavioral factors
      associated with the prevalence of acute symptoms among 150 printing workers in 16
      printing factories in Southern Thailand. Materials and Methods. A cross-sectional
      study was conducted by interviewing 150 printing workers in 16 printing factories
      in Southern Thailand. Results. Acute symptoms comprised dizziness, drowsiness,
      eye irritation, light-headedness, rhinitis, shortness of breath, cough, chest
      tightness, nausea/vomiting, exacerbation of asthma, allergic skin reaction, and
      visual disorder. The prevalence of symptoms was consistently higher among workers
      in the printing process than among other workers. Smoking cigarettes and drinking
      alcohol were not associated with an increased prevalence of acute symptoms among
      these printing-factory workers. Conclusion. The significant associations were
      found between personal protective equipment and personal hygiene and prevalence
      of acute symptoms in printing workers. 

PMID- 25386366
TI  - Long QTc Syndrome Type 2 Presenting in a Postpartum Patient on
      Medroxyprogesterone.
AB  - Introduction. Congenital long QT syndrome type 2 (LQTS2) is a rare inherited
      cardiac abnormality resulting in increased risk of polymorphic ventricular
      tachycardia (PVT). Case Description. A 21-year-old postpartum female presented
      with syncopal episode after phone alarm. She was noted to have PVT on telemetry
      monitoring in the emergency department. EKG revealed QTc of 530. The patient's
      only medication was medroxyprogesterone. She ultimately received a dual chamber
      pacemaker with ICD. Discussion. LQTS2 is associated with alarm sounds as a
      precipitating factor. Postpartum hormonal shifts as well as medroxyprogesterone
      have significant effect on native QTc duration. 

PMID- 25386367
TI  - High-wattage pulsed irradiation of linearly polarized near-infrared light to
      stellate ganglion area for burning mouth syndrome.
AB  - The purpose of this study was to apply high-wattage pulsed irradiation of
      linearly polarized near-infrared light to the stellate ganglion area for burning
      mouth syndrome (BMS) and to assess the efficacy of the stellate ganglion area
      irradiation (SGR) on BMS using differential time-/frequency-domain parameters (D
      parameters). Three patients with BMS received high-wattage pulsed SGR; the
      response to SGR was evaluated by visual analogue scale (VAS) representing the
      intensity of glossalgia and D parameters used in heart rate variability analysis.
      High-wattage pulsed SGR significantly decreased the mean value of VAS in all
      cases without any adverse event such as thermal injury. D parameters mostly
      correlated with clinical condition of BMS. High-wattage pulsed SGR was safe and
      effective for the treatment of BMS; D parameters are useful for assessing
      efficacy of SGR on BMS. 

PMID- 25386368
TI  - Pediatric Cushing's Disease and Pituitary Incidentaloma: Is This a Real
      Challenge?
AB  - Cushing's disease (CD) is the most common cause of endogenous Cushing's syndrome
      in children and adolescents and represents a rare cause of short stature. A 14
      year-old boy came to our attention for progressive weight gain and short stature.
      At examination, height was 140 cm (3rd centile) and weight was 37.7 kg (10th
      centile). Tanner stage was G2, PH 3, testis 3 mL. Hypothyroidism and growth
      hormone deficiency were excluded. A marked increase of urinary free cortisol, a
      nonsuppressible serum cortisol after Liddle 1 test, and an elevated ACTH value
      confirmed the diagnosis of ACTH dependent Cushing's syndrome. Pituitary magnetic
      resonance imaging (MRI) showed a left microadenoma and a right focal area of
      lesser enhancement. Therefore, bilateral inferior petrosal sinus sampling (BIPSS)
      with CRH stimulation was performed to obtain an accurate preoperative
      localization of the adenoma: the interpetrosal sinus ACTH gradient indicated
      lateralization of ACTH secretion to the left side. The patient underwent
      transsphenoidal surgery with selective microadenomectomy, with an immediate ACTH
      decline in the postoperative phase. Histology confirmed the diagnosis of
      corticotrophic pituitary adenoma. Glucocorticoid replacement therapy was
      instituted. Clinical examination demonstrated a rapid catch-up growth (10th
      centile), with a normalization of body mass index and an adequate pubertal
      development. 

PMID- 25386369
TI  - Colonic Dieulafoy's Lesion: A Rare Cause of Lower Gastrointestinal Hemorrhage and
      Review of Endoscopic Management.
AB  - Dieulafoy's lesions are a rare cause of gastrointestinal hemorrhage. Extragastric
      Dieulafoy's lesions are even more uncommon. We report the case of a 75-year-old
      woman who presented with gastrointestinal bleeding from a transverse colonic
      Dieulafoy's lesion. She presented with two episodes of melena followed by one
      episode of fresh blood per rectum. In addition, there was associated presyncope
      and anemia (hemoglobin 69 g/L) in the setting of supratherapeutic warfarin
      anticoagulation (INR 6.2) for nonvalvular atrial fibrillation.
      Esophagogastroduodenoscopy was negative for an upper GI source of bleeding but on
      colonoscopy an actively oozing Dieulafoy's lesion was identified in the
      transverse colon. Bipolar cautery and hemostatic endoclips were applied to
      achieve hemostasis. Clinicians should consider this rare entity as a potential
      cause of potentially life-threatening lower gastrointestinal bleeding and we
      review the endoscopic modalities effective for managing colonic Dieulafoy's
      lesions. 

PMID- 25386370
TI  - A unique case of relapsed B-acute lymphoblastic leukemia/lymphoma as an isolated
      omental mass.
AB  - B-acute lymphoblastic leukemia/lymphoma (B-ALL) is a neoplasm of precursor cells
      committed to the B-cell lineage. Extramedullary involvement is frequent, with
      particular predilection for the central nervous system, lymph nodes, spleen,
      liver, and testis. We report an unusual case of B-ALL relapsing as an isolated
      omental mass along with bone marrow involvement. 

PMID- 25386371
TI  - Unusual case of simultaneous presentation of plasma cell myeloma, chronic
      myelogenous leukemia, and a jak2 positive myeloproliferative disorder.
AB  - Background. Multiple articles discuss the rare incidence and potential causes of
      second hematologic disorders arising after treatment of Chronic Myelogenous
      Leukemia (CML), leading to the theory of imatinib, the current treatment regimen
      for CML, as a possible trigger for the development of secondary neoplasms. Our
      case eliminates the possibility of imatinib as the sole cause since our patient
      received a diagnosis of simultaneous plasma cell myeloma, CML, and a Jak2
      mutation positive myeloproliferative disorder (MPD) arising de novo, prior to any
      treatment. We will further investigate into alternative theories as potential
      causes for multiple hematopathologic disorders. Case Report. There are currently
      no reported cases with the diagnosis of simultaneous plasma cell myeloma, chronic
      myelogenous leukemia, and Jak2 positive myeloproliferative disorder. We present a
      case of a 77-year-old male who was discovered to have these three concurring
      hematopathologic diagnoses. Our review of the literature includes a look at
      potential associations linking the three coexisting hematologic entities.
      Conclusion. The mechanism resulting in simultaneous malignancies is most likely
      multifactorial and potentially includes factors specific to the host, continuous
      stimulation of the immune system, previous chemotherapy or radiation, a potential
      common pluripotent stem cell, or, lastly, preexisting myeloma which may increase
      the susceptibility of additional malignancies. 

PMID- 25386372
TI  - Microscopic Polyangiitis following Silicone Exposure from Breast Implantation.
AB  - We describe a case of a patient who developed microscopic polyangiitis (MPA) in
      the setting of exposure to silicone after breast implantation. A 57-year-old
      Hispanic woman was admitted to our hospital with complaints of fever, cough, and
      hemoptysis. She had undergone silicone breast implantation two years prior to
      presentation. She was diagnosed as having microscopic polyangiitis (MPA) based on
      acute progressive renal failure, hematuria, pulmonary hemorrhage, and positivity
      for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA). A renal biopsy
      performed showed focal segmental necrotizing and crescentic glomerulonephritis.
      The patient received high dose steroids, cyclophosphamide, and plasmapheresis
      with remarkable clinical response. This case report raises the possibility of the
      development of MPA after silicone exposure from breast implantation. 

PMID- 25386373
TI  - Metastatic uterine leiomyosarcoma in the upper buccal gingiva misdiagnosed as an
      epulis.
AB  - Uterine leiomyosarcoma (LMS) is a rare tumor constituting 1% of all uterine
      malignancies. This sarcoma demonstrates an aggressive growth pattern with an high
      rate of recurrence with hematologic dissemination; the most common sites are
      lung, liver, and peritoneal cavity, head and neck district being rarely
      interested. Only other four cases of metastasis in the oral cavity have been
      previously described. The treatment of choice is surgery and the use of adjuvant
      chemotherapy and radiation has limited impact on clinical outcome. In case of
      metastases, surgical excision can be performed considering extent of disease,
      number and type of distant lesions, disease free interval from the initial
      diagnosis to the time of metastases, and expected life span. We illustrate a case
      of uterine LMS metastasis in the upper buccal gingiva that occurred during
      chemotherapy in a 63-year-old woman that underwent a total abdominal hysterectomy
      with bilateral salpingo-oophorectomy for a diagnosis of LMS staged as pT2bN0 and
      that developed lung metastases eight months after primary treatment. Surgical
      excision of the oral mass (previously misdiagnosed as epulis at a dental center)
      and contemporary reconstruction with pedicled temporalis muscle flap was
      performed in order to improve quality of life. Even if resection was achieved in
      free margins, "local" relapse was observed 5 months after surgery.

PMID- 25386374
TI  - A Krukenberg Tumor from an Occult Intramucosal Gastric Carcinoma Identified
      during an Autopsy.
AB  - A healthy 45-year-old Japanese female developed right pleural effusion, ascites,
      and a pelvic mass. Bilateral salpingo-oophorectomy resolved the pleural effusion
      and ascites. Histopathological examination of the ovaries showed bilateral
      Krukenberg tumors with signet-ring cell carcinoma (SRCC). Extensive testing
      including upper and lower gastrointestinal endoscopy and whole-body imaging did
      not detect the primary lesion. Six months after bilateral salpingo-oophorectomy,
      the patient developed multiple osteoblastic bone lesions in the spine, pelvis,
      and femurs. A biopsy of the bone marrow showed SRCC. We administered four cycles
      of S-1 and cisplatin, resulting in the shrinkage of osteoblastic lesions; she
      remained stable for a year. Then, she developed disseminated intravascular
      coagulation with disease progression in the bones. Although she was treated with
      paclitaxel, the disseminated intravascular coagulation progressed, and she died
      in a month. During the autopsy, microscopic examination revealed four foci of
      intramucosal gastric SRCC and healthy macroscopic gastric mucosa. 

PMID- 25386375
TI  - Pseudotumor of ciliary body.
AB  - Orbital pseudotumor is a benign disease involving the orbital structures.
      Pseudotumor of the ciliary body is rare. We present a case of a 27-year-old male
      who presented with gradual visual loss, pain, and redness in his left eye. On
      examination he was found to have a yellowish white mass at the periphery of
      anterior chamber in his left eye and ultrasound biomicroscopy (UBM) revealed a
      ciliary body mass in the same eye. He was treated with systemic steroids, which
      was tapered over a period of 8 weeks. His symptoms improved and the ciliary body
      mass disappeared with no recurrence over the next 6 months. UBM is an important
      diagnostic tool for diagnosing ciliary body mass. Early diagnosis and prompt
      treatment with systemic steroids may help resolve pseudotumor of the ciliary
      body. 

PMID- 25386376
TI  - Radiograms Obtained during Anterior Cervical Decompression and Fusion Can Mislead
      Surgeons into Performing Surgery at the Wrong Level.
AB  - A 68-year-old woman who suffered from C5 nerve palsy because of a C4-5 disc
      herniation was referred to our hospital. We conducted anterior cervical
      decompression and fusion (ACDF) at the C4-5 level. An intraoperative radiogram
      obtained after exposure of the vertebrae showed that the level at which we were
      going to perform surgery was exactly at the C4-5 level. After bone grafting and
      temporary plating, another radiogram was obtained to verify the correct placement
      of the plate and screws, and it appeared to show that the plate bridged the C5
      and C6 vertebrae at the incorrect level. The surgeon was astonished and was about
      to begin decompression of the upper level. However, carefully double-checking the
      level with a C-arm image intensifier before additional decompression verified
      that the surgery was conducted correctly at C4-5. Cautiously double-checking the
      level of surgery with a C-arm image intensifier is recommended when
      intraoperative radiograms suggest surgery at the wrong level. 

PMID- 25386377
TI  - Chondrosternal arthritis in infant: an unusual entity.
AB  - Primary arthritis of chondrosternal joint is very rare and occurs in infants less
      than 18 months of age. Presentation is most often subacute but may be acute.
      Child presents with a parasternal mass with history of fever and/or local signs
      of infection. Clinical symptoms vary from a painless noninflammatory to a painful
      mass with local tenderness and swelling, while fever may be absent. Laboratory
      data show low or marginally raised levels of white blood cells and C-reactive
      protein, reflecting, respectively, the subacute or acute character of the
      infection. It is a self-limiting affection due to the adequate immune response of
      the patient. Evolution is generally good without antibiotherapy with a
      progressive spontaneous healing. A wait-and-see approach with close follow-up in
      the first weeks is the best therapeutic option. 

PMID- 25386378
TI  - Malignant trigeminal nerve sheath tumor and anaplastic astrocytoma collision
      tumor with high proliferative activity and tumor suppressor p53 expression.
AB  - Background. The synchronous development of two primary brain tumors of distinct
      cell of origin in close proximity or in contact with each other is extremely
      rare. We present the first case of collision tumor with two histological distinct
      tumors. Case Presentation. A 54-year-old woman presented with progressive
      atypical left facial pain and numbness for 8 months. MRI of the brain showed left
      middle cranial fossa heterogeneous mass extending into the infratemporal fossa.
      At surgery, a distinct but intermingled intra- and extradural tumor was
      demonstrated which was completely removed through left orbitozygomatic-temporal
      craniotomy. Histopathological examination showed that the tumor had two distinct
      components: malignant nerve sheath tumor of the trigeminal nerve and temporal
      lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein
      53 (TP53) gene mutations were demonstrated in both tumors. Conclusions. We
      describe the first case of malignant trigeminal nerve sheath tumor (MTNST) and
      anaplastic astrocytoma in collision and discuss the possible hypothesis of this
      rare occurrence. We propose that MTNST, with TP53 mutation, have participated in
      the formation of anaplastic astrocytoma, or vice versa. 

PMID- 25386379
TI  - Modified kraske procedure with mid-sacrectomy and coccygectomy for en bloc
      excision of sacral giant cell tumors.
AB  - Sacral giant cell tumors are rare neoplasms, histologically benign but
      potentially very aggressive due to the difficulty in achieving a complete
      resection, their high recurrence rate, and metastization capability. Although
      many treatment options have been proposed, en bloc excision with tumor-free
      margins seems to be the most effective, being associated with long term tumor
      control, improved outcome, and potential cure. An exemplifying case of a 29-year
      old female with progressive complaints of pain and paresthesias in the sacral and
      perianal regions, constipation, and weight loss for 6 months is presented. The
      surgical technique for en bloc excision of a large sacral giant cell tumor
      through a modified Kraske procedure with mid-sacrectomy and coccygectomy is
      described. Complete resection with wide tumor-free margins was achieved. At 5
      years of follow-up the patient is neurologically intact, without evidence of
      local recurrence on imaging studies. A multidisciplinary surgical procedure is
      mandatory to completely remove sacral tumors. In the particular case of giant
      cell tumors, it allows minimizing local recurrence preserving neurovascular
      function, through a single dorsal and definitive approach. 

PMID- 25386381
TI  - Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson's Disease.
AB  - Cognitive impairment and depressive symptoms are of great interest in Parkinson's
      disease (PD), since they are very common and lead to increased disability with
      poor quality of life. Inflammatory mechanisms have been implicated in PD and its
      nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels
      of chemokines in PD patients and to analyze the putative association of
      chemokines with depressive symptoms and cognitive performance. We hypothesized
      that higher chemokines levels are associated with worse cognitive performance and
      increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age-
      and gender-matched controls were subjected to a clinical evaluation including
      cognitive and mood tests. Peripheral blood was drawn and plasma levels of
      CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by
      enzyme-linked immunosorbent assay. PD patients and control individuals presented
      comparable plasma concentrations of all the evaluated chemokines. In PD patients,
      CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging
      scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on
      cognitive tests. Although there was no significant difference between PD patients
      and control individuals regarding chemokines levels, our preliminary results
      showed that CXCL10/IP-10 may be associated with cognitive status in PD. 

PMID- 25386380
TI  - Plasticity-mediated persistence in new and changing environments.
AB  - Baldwin's synthesis of the Organicist position, first published in 1896 and
      elaborated in 1902, sought to rescue environmentally induced phenotypes from
      disrepute by showing their Darwinian significance. Of particular interest to
      Baldwin was plasticity's mediating role during environmental change or
      colonization-plastic individuals were more likely to successfully survive and
      reproduce in new environments than were nonplastic individuals. Once a population
      of plastic individuals had become established, plasticity could further mediate
      the future course of evolution. The evidence for plasticity-mediated persistence
      (PMP) is reviewed here with a particular focus on evolutionary rescue
      experiments, studies on invasive success, and the role of learning in survival.
      Many PMP studies are methodologically limited, showing that preexistent
      plasticity has utility in new environments (soft PMP) rather than directly
      demonstrating that plasticity is responsible for persistence (hard PMP). An ideal
      PMP study would be able to demonstrate that (1) plasticity preexisted
      environmental change, (2) plasticity was fortuitously beneficial in the new
      environment, (3) plasticity was responsible for individual persistence in the new
      environment, and (4) plasticity was responsible for population persistence in
      succeeding generations. Although PMP is not ubiquitous, Baldwin's hypotheses have
      been largely vindicated in theoretical and empirical studies, but much work
      remains. 

PMID- 25386382
TI  - Isolation and Bioactivity Analysis of Ethyl Acetate Extract from Acer tegmentosum
      Using In Vitro Assay and On-Line Screening HPLC-ABTS(+) System.
AB  - The Acer tegmentosum (3 kg) was extracted using hot water, and the freeze-dried
      extract powder was partitioned successively using dichloromethane (DCM), ethyl
      acetate (EA), butyl alcohol (n-BuOH), and water. From the EA extract fraction
      (1.24 g), five phenolic compounds were isolated by the silica gel, octadecyl
      silica gel, and Sephadex LH-20 column chromatography. Based on spectroscopic
      methods such as (1)H-NMR, (13)C-NMR, and LC/MS the chemical structures of the
      compounds were confirmed as feniculin (1), avicularin (2), (+)-catechin (3), (-)
      epicatechin (4), and 6'-O-galloyl salidroside (5). Moreover, a rapid on-line
      screening HPLC-ABTS(+) system for individual bioactivity of the EA-soluble
      fraction (five phenolic compounds) was developed. The results indicated that
      compounds 1 and 2 were first isolated from the A. tegmentosum. The anti
      inflammatory activities and on-line screening HPLC-ABTS(+) assay method of these
      compounds in LPS-stimulated murine macrophages were rapid and efficient for the
      investigation of bioactivity of A. tegmentosum. 

PMID- 25386383
TI  - The Role of RaxST, a Prokaryotic Sulfotransferase, and RaxABC, a Putative Type I
      Secretion System, in Activation of the Rice XA21-Mediated Immune Response.
AB  - Tyrosine sulfation is an important posttranslational modification that determines
      the outcome of serious diseases in plants and animals. We have recently
      demonstrated that the plant pathogen Xanthomonas oryzae pv. oryzae (Xoo) carries
      a functional sulfotransferase (RaxST). raxST is required for activation of rice
      Xa21-mediated immunity indicating the critical, but unknown, function of raxST in
      mediating the Xoo/rice interaction. The raxST gene resides in the same operon
      (raxSTAB) as components of a predicted type I secretion and processing system
      (RaxA and RaxB). These observations suggest a model where RaxST sulfates a
      molecule that contains a leader peptide, which is cleaved by the peptidase domain
      of the RaxB protein and secreted outside the bacterial cell by the RaxABC T1SS. 

PMID- 25386384
TI  - Clarifying the Robust Foundation for and Appropriate Use of DTI in mTBI Patients.
AB  - As clinicians and scientists, we believe scientific evidence and prudent clinical
      practice form the proper basis for determining the utility of diagnostic
      measures, which should subsequently inform forensic use. The misleading and often
      entirely unsubstantiated opinions and positions of Wortzel et al., in opposition
      to DTI as a useful measure in mTBI, are at odds with the clear consensus of the
      scientific literature regarding mTBI, its clinical assessment and natural
      history. The authors' critique contains numerous errors. We will focus on four
      areas: (1) the clinical reality of mTBI (2) the true substance of the scientific
      evidence supporting use of DTI in mTBI, (3) the authors' erroneous and off-target
      opinions regarding DTI analysis and (4) critical appraisal and integration of
      clinical information for diagnosis of mTBI.

PMID- 25386385
TI  - The impact of hospital-acquired conditions on Medicare program payments.
AB  - RESEARCH OBJECTIVE: Hospital-acquired conditions, or HACs, often result in
      additional Medicare payments, generated during the initial hospitalization and in
      subsequent health care encounters. The purpose of this article is to estimate the
      incremental cost to Medicare, as measured by Medicare program payments, of six
      HACs. STUDY DESIGN: The researchers used a matched case-control design to
      determine the incremental increase in Medicare payments attributable to each HAC.
      For each HAC patient, five comparison patients were matched on diagnosis group,
      sex, race, and age. Using the matched sample, we estimated a hospital fixed
      effects log-linear regression on total Medicare payments for the episode of care,
      further controlling for co-morbid conditions. Care episodes included the initial
      hospitalization and all inpatient, outpatient, physician, home health, and
      hospice care that occurred within 90 days of hospital discharge. POPULATION
      STUDIED: All Medicare fee-for-service patients discharged alive from a hospital
      between October 2008 and June 2010 with one of six HACs-severe pressure ulcer,
      fracture, catheter-associated urinary tract infection, vascular catheter
      associated infection, surgical site infection following certain orthopedic
      procedures, or deep vein thrombosis/ pulmonary embolism following certain
      orthopedic procedures-were included in the sample and matched to five similar
      patients without the HACs. PRINCIPAL FINDINGS: The multivariate analysis suggests
      that Medicare paid an additional $146 million per year across these HAC care
      episodes compared with what would have been paid without the HACs. CONCLUSIONS:
      HACs create a significant financial burden for the Medicare program. We compare
      the incremental Medicare payments for these six HACs to the current and upcoming
      Medicare HAC payment penalties.

PMID- 25386386
TI  - Determination of niacin and its metabolites using supercritical fluid
      chromatography coupled to tandem mass spectrometry.
AB  - Niacin, a water-soluble vitamin belonging to the vitamin B group, has been known
      to cause various problems in the human body when deficient. The vitamin is
      derived from the diet and afterwards, niacin and its metabolites are secreted in
      blood or urine. It can be analyzed using liquid chromatography (LC) coupled to
      mass spectrometry, but niacin and its metabolites are very polar compounds.
      Recently, supercritical fluid chromatography (SFC) is gaining attention for polar
      compound analysis. To our best knowledge, the report on the analysis of
      endogenous-very hydrophilic metabolites in biofluids by SFC has not been found.
      In this study, we investigated whether the separation of hydrophilic metabolites
      in biofluids is achievable by SFC. In addition, we also examined the
      applicability of SFC coupled to MS in extrapolating unknown metabolites by means
      of spectra information. As a result, an analysis method to quantify the target
      compounds using SFC/MS/MS was constructed for niacin and its metabolites.
      Additional putative metabolites from niacin were also identified using the MS
      fragmentation spectra in plasma and urine. Consequently, the method using
      SFC/MS/MS allowed for the analysis of polar compounds with low log P ranging from
      -3.7 to 0.29. This study is the first report of the separation of niacin and its
      seven metabolites in human urine and these results showed that SFC-MS/MS can be
      an alternative technique for hydrophilic metabolite analysis. 

PMID- 25386387
TI  - Preferences for health insurance in Germany and the Netherlands - a tale of two
      countries.
AB  - BACKGROUND: This contribution seeks to measure preferences for health insurance
      in Germany and the Netherlands, using two Discrete Choice Experiments (DCE).
      Since the Dutch DCE was carried out right after the 2006 health reform, which
      made citizens explicitly choose a health insurance contract, two research
      questions naturally arise. First, are the preferences with regard to contract
      attributes (such as Managed Care-type restrictions of physician choice),
      incentives (such as bonus options for no claims, deductibles, and a bonus for
      preventive behavior), and extra services provided by the health insurer (such as
      patient counseling) similar between the two countries? Second, was the
      requirement to explicitly choose imposed by the Dutch government in the context
      of the reform effective in reducing status quo bias with respect to future
      reforms? RESULTS: Based on random-effects Probit estimates, these two questions
      can be answered as follows. First, there is resistance against Managed Care-type
      attributes in both populations, but Germans would have to be compensated more for
      giving up free physician choice. Second, their status quo bias is twice as
      important as among their Dutch counterparts, who apparently learned to bear the
      cost of information associated with future choices concerning their health
      insurance. JEL CODES: C25, D12, I18.

PMID- 25386388
TI  - Stated Choice design comparison in a developing country: recall and attribute
      nonattendance.
AB  - BACKGROUND: Experimental designs constitute a vital component of all Stated
      Choice (aka discrete choice experiment) studies. However, there exists limited
      empirical evaluation of the statistical benefits of Stated Choice (SC)
      experimental designs that employ non-zero prior estimates in constructing non
      orthogonal constrained designs. This paper statistically compares the performance
      of contrasting SC experimental designs. In so doing, the effect of respondent
      literacy on patterns of Attribute non-Attendance (ANA) across fractional
      factorial orthogonal and efficient designs is also evaluated. The study uses a
      'real' SC design to model consumer choice of primary health care providers in
      rural north India. A total of 623 respondents were sampled across four villages
      in Uttar Pradesh, India. METHODS: Comparison of orthogonal and efficient SC
      experimental designs is based on several measures. Appropriate comparison of each
      design's respective efficiency measure is made using D-error results.
      Standardised Akaike Information Criteria are compared between designs and across
      recall periods. Comparisons control for stated and inferred ANA. Coefficient and
      standard error estimates are also compared. RESULTS: The added complexity of the
      efficient SC design, theorised elsewhere, is reflected in higher estimated
      amounts of ANA among illiterate respondents. However, controlling for ANA using
      stated and inferred methods consistently shows that the efficient design performs
      statistically better. Modelling SC data from the orthogonal and efficient design
      shows that model-fit of the efficient design outperform the orthogonal design
      when using a 14-day recall period. The performance of the orthogonal design, with
      respect to standardised AIC model-fit, is better when longer recall periods of 30
      days, 6-months and 12-months are used. CONCLUSIONS: The effect of the efficient
      design's cognitive demand is apparent among literate and illiterate respondents,
      although, more pronounced among illiterate respondents. This study empirically
      confirms that relaxing the orthogonality constraint of SC experimental designs
      increases the information collected in choice tasks, subject to the accuracy of
      the non-zero priors in the design and the correct specification of a 'real' SC
      recall period.

PMID- 25386389
TI  - U-SPECT-BioFluo: an integrated radionuclide, bioluminescence, and fluorescence
      imaging platform.
AB  - BACKGROUND: In vivo bioluminescence, fluorescence, and single-photon emission
      computed tomography (SPECT) imaging provide complementary information about
      biological processes. However, to date these signatures are evaluated separately
      on individual preclinical systems. In this paper, we introduce a fully integrated
      bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics
      and image fusion, this integration can help improve understanding of the optical
      imaging (OI) results. METHODS: An OI module was developed for a preclinical SPECT
      system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the
      module for bioluminescence and fluorescence imaging was evaluated in both a
      phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A
      combination of a fluorescent dye and radioactive moiety was used to directly
      relate the optical images of the module to the SPECT findings. Bioluminescence
      imaging (BLI) was compared to the localization of the fluorescence signal in the
      tumors. RESULTS: Both the phantom and in vivo mouse studies showed that
      superficial fluorescence signals could be imaged accurately. The SPECT and
      bioluminescence images could be used to place the fluorescence findings in
      perspective, e.g. by showing tracer accumulation in non-target organs such as the
      liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor
      spread (bioluminescence). CONCLUSIONS: We developed a fully integrated multimodal
      platform that provides complementary registered imaging of bioluminescent,
      fluorescent, and SPECT signatures in a single scanning session with a single dose
      of anesthesia. In our view, integration of these modalities helps to improve data
      interpretation of optical findings in relation to radionuclide images.

PMID- 25386390
TI  - Bone Scan Index as a prognostic imaging biomarker during androgen deprivation
      therapy.
AB  - BACKGROUND: Bone Scan Index (BSI) is a quantitative measurement of tumour burden
      in the skeleton calculated from bone scan images. When analysed at the time of
      diagnosis, it has been shown to provide prognostic information on survival in men
      with metastatic prostate cancer (PCa). In this study, we evaluated the prognostic
      value of BSI during androgen deprivation therapy (ADT). METHODS: Prostate cancer
      patients who were at high risk of a poor outcome and who had undergone bone scan
      at the time of diagnosis and during ADT were recruited from two university
      hospitals for a retrospective study. BSI at baseline and follow-up were
      calculated using an automated software package (EXINIbone(bsi)). Associations
      between BSI, other prognostic biomarkers and overall survival (OS) were evaluated
      using a Cox proportional hazards regression model. RESULTS: One hundred forty-six
      PCa patients were included in the study. A total of 102 patient deaths were
      registered, with a median survival time after the follow-up bone scan of 2.4
      years (interquartile range (IQR) =0.8 to 4.4). Both at baseline and during ADT,
      BSI was significantly associated with OS in univariate and multivariate analyses.
      When BSI was added to a prognostic base model including age, prostate-specific
      antigen, clinical tumour stage and Gleason score, the concordance index increased
      from 0.73 to 0.77 (p =0.0005) at baseline and from 0.77 to 0.82 (p <0.0001)
      during ADT. CONCLUSIONS: Automated BSI during ADT is an independent prognostic
      indicator of OS in PCa patients with bone metastasis. It represents an emerging
      imaging biomarker that can be used in a prognostic model for risk stratification
      of PCa patients at the time of diagnosis and at later stages of the disease. BSI
      could then help physicians identify patients who could benefit from more
      aggressive therapies.

PMID- 25386391
TI  - Pigment-Dispersing Factor Signaling and Circadian Rhythms in Insect Locomotor
      Activity.
AB  - Though expressed in relatively few neurons in insect nervous systems, pigment
      dispersing factor (PDF) plays many roles in the control of behavior and
      physiology. PDF's role in circadian timekeeping is its best-understood function
      and the focus of this review. Here we recount the isolation and characterization
      of insect PDFs, review the evidence that PDF acts as a circadian clock output
      factor, and discuss emerging models of how PDF functions within circadian clock
      neuron network of Drosophila, the species in which this peptide's circadian roles
      are best understood.

PMID- 25386392
TI  - Black henbane and its toxicity - a descriptive review.
AB  - Black henbane (BH) or Hyoscyamus niger, has been used as a medicine since last
      centuries and has been described in all traditional medicines. It applies as a
      herbal medicine, but may induce intoxication accidentally or intentionally. All
      part of BH including leaves, seeds and roots contain some alkaloids such as
      Hyoscyamine, Atropine, Tropane and Scopolamine. BH has pharmacological effects
      like bronchodilating, antisecretory, urinary bladder relaxant, spasmolytic,
      hypnotic, hallucinogenic, pupil dilating, sedative and anti-diarrheal properties.
      Clinical manifestations of acute BH poisoning are very wide which include
      mydriasis, tachycardia, arrhythmia, agitation, convulsion and coma, dry mouth,
      thirst, slurred speech, difficulty speaking, dysphagia, warm flushed skin,
      pyrexia, nausea, vomiting, headache, blurred vision and photophobia, urinary
      retention, distension of the bladder, drowsiness, hyper reflexia, auditory,
      visual or tactile hallucinations, confusion, disorientation, delirium,
      aggressiveness, and combative behavior. The main treatment of BH intoxicated
      patients is supportive therapies including gastric emptying (not by Ipecac),
      administration of activated charcoal and benzodiazepines. Health care providers
      and physicians particularly emergency physicians and clinical toxicologists
      should know the nature, medical uses, clinical features, diagnosis and management
      of BH poisoning. 

PMID- 25386393
TI  - Protective effect of Petroselinum crispum extract in abortion using prostadin
      induced renal dysfunction in female rats.
AB  - OBJECTIVE: Present study investigated the effects of parsley extract on pregnant
      rat kidneys which have undergone clinical abortion using prostaglandins. The
      renal protective effect of parsley extract was evaluated in pregnant rats which
      had an abortion. Parsley was used due to its antioxidant properties. MATERIALS
      AND METHODS: Fifty-four female rats were divided in 9 groups of 6: control
      pregnant, two pregnant groups which received parsley extract and prostadin, two
      non-pregnant groups treated with parsley extract and prostadin, a group
      administered with both treatments, and three groups which received parsley
      extract in pre-implantation, implantation, and post-implantation periods of
      embryos. Ethanolic extract (5 mg/kg) was given daily to animals for 18 days of
      pregnancy period. Parameters such as malondialdehyde (MDA), total antioxidant
      statues (TAS), creatinine, and urea were measured using biochemical assays.
      Histopathologic studies were also done with Hematoxylin-Eosin staining method.
      RESULTS: After 18 days of treatment, significant differences were observed in
      serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed
      edema in prostadin-treated rats while improvements in parsley + prostadin 
      treated rats were observed. CONCLUSION: These results suggested that ethanolic
      extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by
      prostadin-induced abortion and could have beneficial effect in reducing the
      progression of prostaglandin-induced edema.

PMID- 25386394
TI  - Evaluation of antibacterial and anthelmintic activities with total phenolic
      contents of Piper betel leaves.
AB  - OBJECTIVE: The study was conducted to investigate the antibacterial and
      anthelmintic activities and to determine total phenolic contents of methanolic
      extract of Piper betel leaves. MATERIALS AND METHODS: The extract was subjected
      to assay for antibacterial activity using both gram positive and gram negative
      bacterial strains through disc diffusion method; anthelmintic activity with the
      determination of paralysis and death time using earthworm (Pheritima posthuma) at
      five different concentrations and the determination of total phenolic contents
      using the Folin-ciocalteau method. RESULTS: The extract showed significant
      (p<0.01) zone of inhibitions against gram positive Staphylococcus aureus [(6.77+/
      0.25) mm] and Gram negative Escherichia coli [(8.53+/-0.25) mm], Salmonella typhi
      [(5.20+/-0.26) mm], Shigella dysenteriae [(11.20+/-0.26) mm] compared to positive
      control Azithromycin (ranging from 20.10+/-0.17 to 25.20+/-0.35 mm) while no zone
      inhibitory activity was found for both the extract and the standard drug against
      Gram positive Bacillus cereus. The extract also showed potent anthelmintic
      activity requiring less time for paralysis and death compared to the standard
      drug albendazole (10 mg/ml). At concentrations 10, 20, 40, 60 and 80 mg/ml,
      leaves extract showed paralysis at mean time of 9.83+/-0.60, 8.50+/-0.29, 6.60+/
      0.17, 6.20+/-0.44 and 4.16+/-0.60; death at 11.33+/-0.88, 9.67+/-0.33, 7.83+/
      0.17, 7.16+/-0.60 and 5.16+/-0.72 minutes, respectively. Whereas the standard
      drug showed paralysis and death at 19.33+/-0.71 and 51.00+/-0.23 minutes
      respectively. The extract confirmed the higher concentration of phenolic contents
      (124.42+/-0.14 mg of GAE /g of extract) when screened for total phenolic
      compounds. CONCLUSION: As results confirmed potential antibacterial and
      anthelmintic activities of Piper betel leaves extract, therefore it may be
      processed for further drug research.

PMID- 25386395
TI  - Hepatoprotective effect of Crocus sativus (saffron) petals extract against
      acetaminophen toxicity in male Wistar rats.
AB  - OBJECTIVES: Acetaminophen (APAP) toxicity is known to be common and potentially
      fatal. This study aims to investigate the protective effects of hydroalcoholic
      extract, remaining from Crocus sativus petals (CSP) against APAP-induced
      hepatotoxicity by measuring the blood parameters and studying the histopathology
      of liver in male rats. MATERIALS AND METHODS: Wister rats (24) were randomly
      assigned into four groups including: I) healthy, receiving normal saline; II)
      Intoxicated, receiving only APAP (600 mg/kg); III) pre-treated with low dose of
      CSP (10 mg /kg) and receiving APAP (600 mg/kg); IV) pre-treated with high dose of
      CSP (20 mg/kg) and receiving APAP (600 mg/kg). RESULTS: The APAP treatment
      resulted in higher levels of alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), and bilirubin, along with lower total protein and albumin
      concentration than the control group. The administration of CSP with a dose of 20
      mg/kg was found to result in lower levels of AST, ALT and bilirubin, with a
      significant higher concentration of total protein and albumin. The
      histopathological results regarding liver pathology, revealed sever conditions
      including cell swelling, severe inflammation and necrosis in APAP-exposed rats,
      which was quiet contrasting compared to the control group. The pre-treated rats
      with low doses of ?CSP showed hydropic degeneration with mild necrosis in
      centrilobular areas of the liver, while the same subjects with high doses of ?CSP
      appeared to have only mild hepatocyte degeneration. CONCLUSIONS: Doses of 20
      mg/kg of CSP ameliorates APAP-induced acute liver injury in rats. It was
      concluded that the antioxidant property of CSP resulted in reducing the oxidative
      stress complications of toxic levels of APAP in intoxicated rats.

PMID- 25386396
TI  - Evaluating the effects of galbanic acid on hydrogen peroxide-induced oxidative
      DNA damage in human lymphocytes.
AB  - OBJECTIVE: Ferula szowitsiana has been widely used for medicinal purposes around
      the world. The anti-oxidant effect of F. szowitsiana had been proved. The current
      study aims to determine the protective effects of galbanic acid, a sesquiterpene
      coumarin from F. szowitsiana, against hydrogen peroxide (H2O2) - induced
      oxidative DNA damage in human lymphocytes. MATERIALS AND METHODS: Human
      lymphocytes were incubated with H2O2 (0, 25, 50, 100, and 200 uM), galbanic acid
      (200 and 400 uM) and a combination of galbanic acid (200 and 400 uM) and H2O2 (25
      uM) at 4 C for 30 minutes. Solvents of galbanic acid without H2O2 were used as
      negative controls. RESULTS: The findings of this study demonstrated that H2O2
      exposure leads to a significant concentration-dependent increase in DNA damage.
      Galbanic acid did not cause DNA damage compared with the control cells. Data
      showed that galbanic acid does not have a protective effect against H2O2-induced
      oxidative DNA damage in human lymphocytes. CONCLUSION: According to the results,
      it is concluded that the capability of F. szowitsiana in reducing reactive oxygen
      species and the anti-inflammatory property of its methanolic extract may be due
      to its other ingredients.

PMID- 25386397
TI  - Free radical scavenging capacity and antioxidant activity of methanolic and
      ethanolic extracts of plum (Prunus domestica L.) in both fresh and dried samples.
AB  - OBJECTIVES: Consumption of fruits, such as plums and prunes, is useful in
      treating blood circulation disorder, measles, digestive disorder, and prevention
      of cancer, diabetes, and obesity. The paper presents a description of antioxidant
      and antiradical capacity of plum (Prunus domestica L.) in both fresh and dried
      samples. MATERIALS AND METHODS: Samples were mixed with methanol and ethanol (as
      solvents) and were extracted on magnetic shaker, separately. The experiments were
      carried out to measure the Total Phenolic Content (TPC), Total Flavonoid Content
      (TFC), Total Antioxidant Capacity (TAC), Reducing Power Assay (RPA), Chain
      Breaking Activity (CBA), and quantity of Malondialdehyde (MDA), 2,2-Diphenyl-1
      Picrylhydrazyl (DPPH),Nitric Oxide (NO),Hydrogen peroxide (H2O2) and
      superoxide(O2 (-)) radicals inhibition. RESULTS: The results showed that the
      highest values for the TPC, TFC,TAC, RPA, CBA, DPPH, and NO were related to
      ethanolic extractsof dried sample which showed statistically significant
      differences (p<0.01 and p<0.0001), while the maximum values for the H2O2 and O2 (
      )were related to ethanolic extracts of fresh sample. The correlations data were
      analyzed among all parameters and the TPC and TFC had a significant correlation
      (r(2)=0.977). Moreover, it was found that methanol was more successful in
      extraction procedure than ethanol (p<0.01). CONCLUSION: Findings suggest that the
      fresh samples are more successful in collecting oxygen free radicals such as
      superoxide (O2 (-)) and peroxy radicals (ROO(.)) than dried.

PMID- 25386398
TI  - Lipid-lowering activity of Cow urine ark in guinea pigs fed with a high
      cholesterol diet.
AB  - OBJECTIVES: Cow urine ark (CUA), known as "Amrita" as mentioned in Ayurveda,
      contains anti-hyperglycemic and antioxidant effects. Therefore, we designed the
      present study to evaluate the lipid lowering activity of CUA and its possible
      implication in metabolic syndrome. MATERIALS AND METHODS: Thirty guinea pigs of
      either sex were divided into five groups: Group 1 and 2 serving as a vehicle and
      sham control, received normal and high fat diet for 60 days respectively; Group
      3, 4 and 5 received high fat diet for 60 days with CUA 0.8 ml/kg, 1.6 ml/kg and
      rosuvastatin (1.5 mg/kg) on thelast 30 days of study period, respectively. Serum
      lipid profile (total cholesterol, triglycerides, LDL-C, VLDL-C, HDL-C, total
      Cholesterol/HDL-C) and serum enzymes (ALT, AST, ALP, LDH and CK-MB) were
      performed in each group at the beginning and end of the study. Histological study
      of liver and kidney was done in each group. RESULTS: CUA (0.8 ml/kg)
      significantly decreased the serum triglycerides and VLDL-C, but CUA (1.6 ml/kg)
      decreased the total serum Cholesterol, triglycerides and VLDL-C (p < 0.05).
      Higher dose (1.6 ml/kg) of CUA also increased HDL-C level, significantly (p <
      0.05). CUA reduced serum AST, ALP and LDH level, which was statistically
      significant as well, while it also decreased the accumulation of lipid in
      hepatocytes as compared to sham control. CONCLUSIONS: CUA reduced triglycerides,
      increased HDL-C and found to be hepatoprotective in animals that are on a high
      fat diet.

PMID- 25386399
TI  - Ethnobotanical studies on plant resources of Mangowal, District Gujrat, Punjab,
      Pakistan.
AB  - OBJECTIVE: This study was conducted to collect indigenous traditional knowledge
      about the medicinal plants and their uses in Mangowal, District Gujrat, Punjab,
      Pakistan. MATERIALS AND METHODS: The ethnomedicinal data were gathered through
      questionnaires and extensive personal dialogues with native individuals
      comprising 40 males and 20 females of diverse age groups between 50 to 80 years
      and also tabibs and hakims. Ethnobotanical investigations were directed from
      January 2013 to March 2013 under the acquiescence of university of Gujrat (UOG),
      Punjab, Pakistan. RESULTS: About 40 plant species belonging to 22 families were
      investigated which are utilized by native people to cure various disorders and
      ailments such as asthma, ulcer, gonorrhea, piles, stomach pain, and skin
      diseases. Medicinal plants comprises of combination of active compounds which are
      side effect neutralizing and synergistic. Herbal medicines were prepared from
      different part of plants. Mostly used plant parts were leaves, fruits, barks,
      roots, seeds, and sometimes whole plant. CONCLUSION: The results demonstrated
      that the area is rich in vegetation but remained botanically virgin and not
      explored extensively and intensively.

PMID- 25386400
TI  - The effects of Artemisia deserti ethanolic extract on pathology and function of
      rat kidney.
AB  - OBJECTIVES: Medicinal plants played an important role in human health. The kidney
      is a major organ for elimination the additional materials of body. Some of
      metabolic waste products are excreted through the kidneys, give us useful
      information about kidney health. Therefore, the aim of this research was to study
      the effects of A. deserti flowering tips extract on kidney. MATERIALS AND
      METHODS: Three groups of animal were studied. Wistar rats were divided into three
      groups. Group 1 was injected with saline, group 2 and 3 were injected with
      extract, 100 mg/kg and 200 mg/kg, respectively. The animals were anesthetized,
      blood samples were collected 2 days after the last injection, then urea, uric
      acid and creatinine levels were assayed. Also, the kidney histology was studied.
      RESULTS: No significant changes in urea and uric acid were observed. But,
      creatinine concentration was changed significantly in group 3 compared to other
      groups. The extract caused histologic changes in the kidney, including,
      glomerular atrophy, congestion of inflammatory cells and degeneration of the
      renal tubules. CONCLUSION: The results showed that A. deserti extract was able to
      damage the kidney tissue. However, the reason for these histopathological changes
      remains to be clarified.

PMID- 25386401
TI  - Khaya senegalensis inhibits piroxicam mediated gastro-toxicity in wistar rats.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of piroxicam
      co-administration with ethanolic stem-bark extract of Khaya senegalensis on
      biomarkers of oxidative stress and gastro-toxicity in Wistar rats. MATERIALS AND
      METHODS: Thirty healthy male and female Albino Wistar rats (190-220 g) were
      grouped into six (n = 5) with designated treatments including: Normal saline,
      piroxicam (20 mg/kg), extract (200 and 400 mg/kg) alone and both doses of the
      extract co-administered with piroxicam. The drugs were administered orally to all
      the rats for fourteen consecutive days and on the fifteenth day, they were
      euthanized with chloroform inhalation. Blood samples and the stomachs were
      isolated for evaluation of the oxidative stress biomarkers and gastro integrity,
      respectively. RESULTS: The results of the study revealed that the levels of
      oxidative stress markers didn't differ significantly between the groups receiving
      the extract alone, the extract in combination or piroxicam alone. Gross and
      histological observations of the stomach showed gastric mucosal changes and mild
      atrophic lesions in the piroxicam group only. CONCLUSION: This study illustrates
      the interaction of Khaya senegalensis and piroxicam results in the gastro
      protective beneficial effects. The extract's outcome on various prostaglandin
      levels and synthesis is being considered towards possible elucidation regarding
      the exact mechanism of cytoprotection.

PMID- 25386402
TI  - The efficacy of hydro alcoholic extract of Seidlitzia rosmarinus on experimental
      zoonotic cutaneous leishmaniasis lesions in murine model.
AB  - OBJECTIVE: Leishmaniasis is one of the most important parasitic infectious
      diseases in the world. Since last century, many efforts have been made to control
      and treat the disease, but appropriate vaccines, pesticides and medicines are not
      available or even eligible. The purpose of this study was to evaluate the effect
      of hydro-alcoholic extract of Seidlitzia rosmarinus on the lesions of
      experimental Cutaneous Leishmaniasis (CL) in Balb/c mice. MATERIALS AND METHODS:
      The population study was 60 Ballb/c mice which divided to 6 groups, all infected
      with Leishmania major [MRHO/75/IR]. Soon after the ulcer started to appear in the
      early stage, a dose of provided herbal extract with 5, 10 and 15% concentration
      applied on each lesion. The surface area of the lesions measured during an
      interval of 10 days. Direct Giemsa stained smears prepared two and four weeks
      after treatment. RESULTS: Increasing the mean size of the lesions was
      statistically significant compared to those in control group (p>0.001). Visceral
      Leishmaniasis (VL) developed in all of the mice including the control group that
      received Eucerine alone. Survival rate in group receiving 15% S. rosmarinus
      extracts showed significantly higher compared to mice in control group (p<0.001).
      CONCLUSION: Hydro-alcoholic extracts of S.rosmarinus with concentrations below15%
      did not show a therapeutic effect on experimental CL ulcers of Balb/c mice.
      Further studies with higher concentrations or nano particles are recommended.

PMID- 25386403
TI  - Renoprotective effect of hydroalcoholic extract of Rheum ribes root in diabetic
      female rats.
AB  - OBJECTIVE: Medical plants, as rich sources of natural antioxidants with
      antidiabetic effects, are used worldwide to diminish a variety of symptoms and
      many diseases. R. ribes L., which belongs to the family of polygonaceae, can
      provide symptomatic relief and assist in the prevention of the secondary
      complications of the diabetes. MATERIAL AND METHODS: 36 female adult rats were
      randomly divided into 6 groups of 6. Normal Control groups treated with normal
      saline. Positive control groups treated with hydroalcohlic extract of R. ribes
      root (150 mg/kg) daily by gavages for 4 consecutive weeks. Diabetes was inducedby
      injection of 120 mg/kg alloxan monohydrate intraperitoneally. Two diabetic groups
      were treated with different doses of R. ribes root extract. The sixth diabetic
      groups were treated with glibenclamide (0.6 mg/kg). At the end of 28 days, blood
      samples were collected and their kidney tissues were processed for light
      microscopy. RESULTS: The results showed that hydro-alcoholic extract of R. ribes
      decreased the level of glucose, cholesterol, triglyceride, urea and creatinine in
      diabetic rats (p<0.05) in compared with diabetic rats, while the level of HDL
      increased at the same group (p<0.05). Histopathological changes of kidney samples
      were comparable with respective control. In diabetic rats, kidney sections showed
      atrophy of glomerular capillaries with increased Bowman's space and acute tubular
      necrosis. The groups that were treated with R. ribes root were improved towards
      normal condition. CONCLUSION: It is interesting to note that hydroalcohlic
      extract of R. ribes root improves renal dysfunction in alloxan-induced diabetic
      rats through controlling blood glucose and renal protective effects.

PMID- 25386404
TI  - Ethnobotanical study of medicinal plants used in Arjan - Parishan protected area
      in Fars Province of Iran.
AB  - Objective : Today, medicinal plants are widely used in remedies for several
      ailments and improvement of human health because of their pharmaceutical
      properties. This study aimed to document important useful medicinal plants and
      their medicinal characteristics for treatment of human ailments in the Arjan (_)
      Parishan protected area in Fars province of Iran during 2010-2012. Materials and
      Methods : Data were obtained using direct interviews with 80 informants
      particularly those who were more familiar with the herbs and their medicinal
      properties. Collected plants were recognized and families, genera, and species
      determined using indispensable references. In this paper, scientific name, local
      name, parts used, and ways of application and ailments treated using traditional
      medicinal plant species have been provided. Results : We documented 85 plant
      species belonging to 39 families and 78 genera used for treating ailments. Among
      which, Asteraceae with 13 species was the most frequently used family and fruits
      and leaves were the favored parts for local users. Our results indicated that in
      this area, the highest compliance in the use of plants in treating ailments were
      related to the intestinal digestive system (40.8%). Conclusion : The present
      study is the first contribution to the ethnobotany of this region. Our results
      showed that some plants are used for medicinal purposes in this region, either
      for the same or for different purposes. Generally, the results of the present
      investigation can be used as a basis for selecting useful medicinal plants and
      also help to preserve precious information that may otherwise be lost to future
      generations. 

PMID- 25386405
TI  - Effects of Hypericum perforatum extract on IgG titer, leukocytes subset and
      spleen index in rats.
AB  - OBJECTIVES: Hypericum perforatum L. is a medicinal plant containing many
      polyphenolic compounds, including flavonoids and phenolic acids with
      antidepressant and anti-inflammatory properties. This study was investigated the
      effects of Hypericum perforatum extract (HPE) on immunity, body weight (BW), and
      spleen index (SI) in rats. MATERIALS AND METHODS: A total of 24 Wistar male rats
      were randomly received 4 different doses (6 rats each) of HPE (0, 100, 200 and
      400 mg/kg BW) intraperitoneally for 14 days using a completely randomized design.
      On days 1 and 7, rats were received 0.5 ml SRBC (10%) injection. Blood samples
      were collected on day 14 to evaluate IgG titer and leukocyte count. On days 1, 7
      and 14, the BW and on day 14 spleen were weighted for SI.  RESULTS: The IgG titer
      increased with higher doses of HPE. The HPE increased number of lymphocytes at
      200 mg but decreased at 400 mg, number of neutrophils decreased at 200 mg but
      increased at 400 mg, and number of monocytes increased at 100 mg and 200 mg but
      decreased at 400 mg (p<0.01). Increasing doses of HPE lowered BW (p<0.01). The
      HPE increased SI at 100 mg and 200 mg but decreased at 400 mg (p>0.072). 
      CONCLUSIONS: The results showed that HPE slightly improved IgG titer but
      significantly increased the number of leukocytes and monocytes at 200 mg, and
      neutrophils at 400 mg. The HPE decreased BW at 100 mg and 200 mg with no damage
      on spleen. 

PMID- 25386406
TI  - Evaluation of possible toxic effects of spearmint (Mentha spicata) on the
      reproductive system, fertility and number of offspring in adult male rats.
AB  - OBJECTIVE: In this study we investigated the effects of spearmint (Mentha spicata
      Labiatae) on the reproductive system, fertility and number of offspring in adult
      male rats. MATERIALS AND METHODS: Adult Wistar male rats in one control (C) and
      three experimental groups (I, II and III) received 0, 10, 20 and 40 mg/kg
      spearmint extract orally for 45 days, respectively. Following this treatment, the
      animals' weights, and the standard weight of reproductive tissues, sperm count,
      sperm motility and serum testosterone concentration were measured, and
      reproductive tissues were examined histopathologically. To evaluate the effects
      of spearmint on fertility of male rats and growth of their offspring, male rats
      of the control and experimental groups mated with untreated female rats. RESULTS:
      RESULTS showed that spearmint did not affect the rats' body and reproductive
      tissue weights. The sperm count, fast and slow progressive motility of sperm and
      serum testosterone concentration decreased while number of non-progressive sperm
      and immotile sperm increased in the experimental groups compared to the control
      group, but none of these changes were statistically significant.
      Histopathological studies showed no severe changes in reproductive tissues
      between control and experimental groups. Number and growth of offspring born from
      mating of male rats with untreated female rats showed no difference. CONCLUSION:
      We concluded that spearmint has no significant toxic effect on the reproductive
      system, fertility and number of offspring in adult male rats at the above
      mentioned dose levels. However high levels of this extract may have adverse
      effects on male fertility.

PMID- 25386407
TI  - Evaluation of thrombolytic potential of three medicinal plants available in
      Bangladesh, as a potent source of thrombolytic compounds.
AB  - OBJECTIVE: The present study is aimed to investigate in vitro thrombolytic
      activity of three Bangladeshi medicinal plants Averrhoa bilimbi (Oxalidiaceae),
      Clerodendrum viscosum (Verbanaceae) and Drynaria quercifolia (Polypodiaceae).
      MATERIALS AND METHODS: Each the plant was extracted with methanol at room
      temperature and the concentrated methanolic extracts (MEF) were fractionated by
      the modified Kupchan partitioning method to render pet-ether soluble fraction
      (PESF), carbon tetrachloride soluble fraction (CTSF), chloroform soluble fraction
      (CSF) and aqueous soluble fraction (AQSF). To observe their thrombolytic
      potential, a prompt and swift method was involved where streptokinase and water
      were used as positive and negative control, respectively. RESULT: Among the three
      plants, AQSF and PESF of D. quercifolia with CTSF of C. viscosum exhibited
      highest thrombolytic activity by clot lysis of 34.38%, 34.27% and 28.64%,
      respectively. Among other extracts A. bilimbi, C. viscosun and D.quercifolia
      showed significant percentage (%) of clot lysis compared to standard
      streptokinase (41.05%) while the negative control water revealed 3.31 % lysis of
      clot. CONCLUSION: From our findings it is observed that all the plants revealed
      remarkable thrombolytic activity. Therefore, steps should be taken to observe in
      vivo clot dissolving potential and to isolate active component(s) of these
      extracts.

PMID- 25386409
TI  - The evolution of prostate cancer therapy: targeting the androgen receptor.

PMID- 25386410
TI  - Development of a nomogram model predicting current bone scan positivity in
      patients treated with androgen-deprivation therapy for prostate cancer.
AB  - PURPOSE: To develop a nomogram predictive of current bone scan positivity in
      patients receiving androgen-deprivation therapy (ADT) for advanced prostate
      cancer; to augment clinical judgment and highlight patients in need of additional
      imaging investigations. MATERIALS AND METHODS: A retrospective chart review of
      bone scan records (conventional (99m)Tc-scintigraphy) of 1,293 patients who
      received ADT at the Memorial Sloan-Kettering Cancer Center from 2000 to 2011.
      Multivariable logistic regression analysis was used to identify variables
      suitable for inclusion in the nomogram. The probability of current bone scan
      positivity was determined using these variables and the predictive accuracy of
      the nomogram was quantified by concordance index. RESULTS: In total, 2,681 bone
      scan records were analyzed and 636 patients had a positive result. Overall, the
      median pre-scan prostate-specific antigen (PSA) level was 2.4 ng/ml; median PSA
      doubling time (PSADT) was 5.8 months. At the time of a positive scan, median PSA
      level was 8.2 ng/ml; 53% of patients had PSA <10 ng/ml; median PSADT was 4.0
      months. Five variables were included in the nomogram: number of previous negative
      bone scans after initiating ADT, PSA level, Gleason grade sum, and history of
      radical prostatectomy and radiotherapy. A concordance index value of 0.721 was
      calculated for the nomogram. This was a retrospective study based on limited data
      in patients treated in a large cancer center who underwent conventional (99m)Tc
      bone scans, which themselves have inherent limitations. CONCLUSION: This is the
      first nomogram to predict current bone scan positivity in ADT-treated prostate
      cancer patients, providing high predictive accuracy.

PMID- 25386408
TI  - Endoplasmic reticulum chaperones and oxidoreductases: critical regulators of
      tumor cell survival and immunorecognition.
AB  - Endoplasmic reticulum (ER) chaperones and oxidoreductases are abundant enzymes
      that mediate the production of fully folded secretory and transmembrane proteins.
      Resisting the Golgi and plasma membrane-directed "bulk flow," ER chaperones and
      oxidoreductases enter retrograde trafficking whenever they are pulled outside of
      the ER by their substrates. Solid tumors are characterized by the increased
      production of reactive oxygen species (ROS), combined with reduced blood flow
      that leads to low oxygen supply and ER stress. Under these conditions, hypoxia
      and the unfolded protein response upregulate their target genes. When this
      occurs, ER oxidoreductases and chaperones become important regulators of tumor
      growth. However, under these conditions, these proteins not only promote the
      folding of proteins, but also alter the properties of the plasma membrane and
      hence modulate tumor immune recognition. For instance, high levels of
      calreticulin serve as an "eat-me" signal on the surface of tumor cells.
      Conversely, both intracellular and surface BiP/GRP78 promotes tumor growth. Other
      ER folding assistants able to modulate the properties of tumor tissue include
      protein disulfide isomerase (PDI), Ero1alpha and GRP94. Understanding the roles
      and mechanisms of ER chaperones in regulating tumor cell functions and
      immunorecognition will lead to important insight for the development of novel
      cancer therapies. 

PMID- 25386412
TI  - Evaluation of proximal femoral geometry in plain anterior-posterior radiograph in
      eastern-Indian population.
AB  - BACKGROUND: The morphologic features of the proximal femur are used in
      preoperative planning prior to total hip arthroplasty. The standard commercially
      available marketed prostheses sometimes may not be the best fit to all subjects
      because of the large anatomic variation among different population. Orthopaedic
      surgeons always stress the need for a proper implant-patient match in hip joint
      replacements to avoid post-operative complication of mismatch which may affect
      the ultimate outcome of the operation. AIM: The present study was undertaken to
      measure the important parameters of upper end of femur in elderly Eastern Indian
      population which will help the prosthetist to manufacture ideal implant for the
      local population. This will also help the orthopaedic surgeons while positioning
      the implants during total hip replacement (THR) procedure in this population.
      MATERIALS AND METHODS: Measurements were made on both sides, left and right from
      anterior-posterior radiograph of 102 subject (>50yrs, 42 male and 60 females)
      using AGFA software. Three parameters femoral head diameter (FHD), neck-shaft
      angle (NSA) and horizontal off-set (HO) were measured. RESULTS: SPSS software
      used for data analysis. Gender- wise no significant differences were found in NSA
      and FHD, but HO was significantly lower in female than that of male (p<.05).The
      values on both sides didn't differ significantly. CONCLUSION: Improved knowledge
      of the morphology of the proximal femora will assist the surgeon in restoring the
      geometry of the proximal femur during total hip arthroplasty and the data could
      be used as a guideline to design a more suitable implant for Eastern Indian
      population.

PMID- 25386411
TI  - Interrelationship between type three secretion system and metabolism in
      pathogenic bacteria.
AB  - Before the advent of molecular biology methods, studies of pathogens were
      dominated by analyses of their metabolism. Development of molecular biology
      techniques then enabled the identification and functional characterisation of the
      fascinating toolbox of virulence factors. Increasing, genomic and proteomic
      approaches form the basis for a more systemic view on pathogens' functions in the
      context of infection. Re-emerging interest in the metabolism of pathogens and
      hosts further expands our view of infections. There is increasing evidence that
      virulence functions and metabolism of pathogens are extremely intertwined. Type
      three secretion systems (T3SSs) are major virulence determinants of many Gram
      negative pathogens and it is the objective of this review to illustrate the
      intertwined relationship between T3SSs and the metabolism of the pathogens
      deploying them. 

PMID- 25386413
TI  - Morphometric study of the styloid process of temporal bone.
AB  - OBJECTIVE: Styloid process of temporal bone is clinically important, because
      variations in length, as well as the angulations of styloid process are
      associated with the symptoms of stylalgia (Eagle's syndrome) and the surgical
      excision of the process could alleviate neck and cervicofacial pain in patients.
      This study was aimed to evaluate the length, angulation and distance between
      bases and tips of the styloid process. MATERIALS AND METHODS: We studied 114 dry
      skull bones with intact styloid processes. The length of styloid process and
      distance between bases and tips of the styloid process were measured with the
      help of vernier calipers. The angulation (anterior and medial angles) of the
      styloid process was measured directly from the digital images by the image
      analysis using Adobe Photoshop 7.0 and Image Tool 3.0 Program. A styloid process
      longer than 3 cm was identified as an elongated styloid process. RESULTS: The
      means of length of styloid process, distance between bases and tips of styloid
      process were 2.58 cm, 6.80 cm and 4.65 cm respectively, while means of anterior
      and medial angles were 62.45(o) and 74.15(o), respectively. Significant
      statistical difference was seen in anterior angles between groups with normal and
      elongated styloid processes (p>0.001). CONCLUSION: Anterior angulation and
      distance between bases and tips decreased in elongated styloid processes while
      medial angulation showed no significant change. Our findings highlight the
      importance of the examination of styloid process in patients with symptoms of
      stylalgia.

PMID- 25386414
TI  - Anencephaly and its associated malformations.
AB  - INTRODUCTION: Anencephaly is a serious neural tube defect in which parts of the
      brain and skull are not developed. But apart from this it is also associated with
      other malformations which are not related to neural tube in development. AIM: The
      present study was undertaken to find the associated congenital malformations in
      western region of India and establish a aetiological correlation. MATERIALS AND
      METHODS: The study was conducted using 20 anencephalic fetuses. RESULTS: Nearly
      80% of fetuses had associated malformations. Spina bifida was seen in 9 fetuses
      and cleft palate in 8. Female fetus with cleft palate had other severe associated
      gastrointestinal and skeletal malformation. CONCLUSION: In cases of anencephaly
      other associated malfor-mations like spina bifida and cleft palate are commonly
      seen.

PMID- 25386415
TI  - Anatomical Study of Pterygospinous and Pterygoalar Bar in Human Skulls with their
      Phylogeny and Clinical Significance.
AB  - BACKGROUND: Pterygospinous and pterygoalar ligaments present at the cranial base
      may sometimes get ossified leading to the formation of complete or incomplete
      bony bars in relation to foramen ovale. These are of clinical importance because
      these may obliterate the foramen ovale causing mandibular neuralgia. They may
      cause trouble in performing thermocoagulation and anaesthesia for trigeminal
      neuralgia. They may pose surgical difficulty in approaching the retro and
      parapharyngeal spaces and hence the anatomy of these bony bars is very important.
      MATERIALS AND METHODS: The present study was conducted in 100 dry human skulls of
      unknown sex to know the incidence, side, degree of ossification (complete/
      incomplete) and relation of the pterygospinous and pterygoalar bars to the
      foramen ovale. RESULTS: Pterygospinous and pterygoalar bars were seen in 41
      skulls which were classified into Type I (26.83%), Type II (58.54%) and Type III
      (14.63%) based on the presence of pterygospinous bar, pterygoalar bar or both
      together. Pterygospinous bars were seen in 17 skulls of which, one skull (5.88%)
      had complete and 16 skulls (94.12%) showed incomplete bars. Out of the 30 skulls
      with pterygoalar bars, complete bar was seen in one (3.33%) and incomplete in 29
      skulls (96.67%). These bars were seen more on the left side of the skull than on
      the right. They were in close relation to the foramen ovale; the pterygospinous
      bar was inferior or medial to foramen ovale and pterygoalar bar was lateral,
      inferior or medial to the foramen ovale. CONCLUSION: The presence of the
      pterygospinous and pterygoalar bars cause variety of symptoms due to
      neurovascular entrapment and also obstruct surgical approaches to the base of
      skull. Hence the anatomical knowledge of these osseous bars is essential for
      anaesthetists, radiologists, dentists and neurosurgeons to increase the success
      of diagnostic evaluation and surgical approaches to the cranial base.

PMID- 25386416
TI  - Premature ejaculation - dose and duration dependent effect of fluoxetine: a
      histological study on seminal vesicle of albino rats.
AB  - INTRODUCTION: Fluoxetine is a prototype drug of Selective Serotonin Reuptake
      Inhibitors. Its active demethylated metabolite has a half life of 7-10 d.
      Fluoxetine is used to treat depression and is also prescribed in premature
      ejaculation. AIM: In the present study dose and duration dependent effects of
      Fluoxetine on histology of seminal vesicle of the albino rats were observed.
      MATERIALS AND METHODS: The present study was conducted on 36 adult male albino
      rats. Fluoxetine was administered intraperitoneally for 2 wk, 4 wk and 12 wk with
      mild (10mg/kg/day), moderate (20mg/kg/day) and severe doses (40mg/kg/day).
      Histological slides of Seminal vesicle were prepared and stained with Hematoxylin
      and Eosin stain. RESULTS: On examination through the light microscope, the
      proliferation of primary, secondary and tertiary villi, increased crypt/alveoli,
      increased thickness of lamina propria, decreased epithelial cell height,
      metaplasia, changes in the amount of luminal eosinophilic secretory material in
      the form of scanty secretion in lumen of seminal vesicle. CONCLUSION: Low doses
      for long duration and high doses for short duration of Fluoxetine produce
      histological changes in seminal vesicle of albino rats.

PMID- 25386417
TI  - A lobulated spleen with multiple fissures and hila.
AB  - During our dissection classes, we observed a lobulated spleen with multiple hila
      and fissures. The spleen presented 4 hila and 5 deep fissures. The hila were seen
      on the visceral surface. The fissures extended into the substance of the spleen
      from superior border, inferior border and the visceral surface. Because of these
      fissures, the spleen appeared to be lobulated, having seven distinct
      lobes/lobules. Knowledge of this variation could be useful to the radiologists
      and surgeons. 

PMID- 25386418
TI  - A Rare Presentation of Os Odontoideum with Multiple Vertebral Fusion in Type III
      Klippel-Feil Syndrome (KFS) - A Case Report.
AB  - An abnormal atlas and axis with presence of os odontoideum and fusion of multiple
      vertebrae were noted in an intact skeleton, in the osteology museum of the
      Department of Anatomy of North Bengal Medical College, West Bengal, India.These
      multiple abnormalities at various levels along with increased thickness of antero
      posterior arch of atlas pointed towards the congenital nature of the anomalies,
      possibly due to Klippel-Feil syndrome (KFS). These unusual findings denote a
      developmental background of the manifestations.The cervical instability,
      resultant neurodeficit and impairment of quality of life of the affected
      individuals, which are inherent in such cases, reveal their clinical importance. 

PMID- 25386419
TI  - Bilateral absence of musculocutaneous nerve: a case report.
AB  - Detailed knowledge of course and distribution of nerves in the axilla and arm is
      very important in the management of nerve injuries particularly in case of their
      variations. Bilateral absence of the musculocutaneous nerve was found during
      routine dissection in a male cadaver. The dissected part was cleared to see the
      distribution of the muscles of the arm. The muscles of the flexor compartment
      were supplied by the median nerve, instead of the musculocutaneous nerve. The
      present case report of this anatomical variation of the nerves should help in
      management of nerve injuries in the axilla or the arm. 

PMID- 25386420
TI  - Effect of Different Phases of Menstrual Cycle on Reflection Index, Stiffness
      index and Pulse wave velocity in Healthy subjects.
AB  - INTRODUCTION: Arterial compliance will result in stabilizing the fluctuations in
      arterial pressure and blood flow. So arterial stiffness can be a good indicator
      for monitoring the cardiovascular system. Arterial stiffness can be measured
      using indices like reflection index (RI), stiffness index (SI) and Brachial
      Finger Pulse Wave Velocity (BFPWV). OBJECTIVES: Aim of our study was to evaluate
      the changes in RI, SI and BFPWV during different phases of the menstrual cycle
      and to correlate RI with SI in healthy female subjects between the age group of
      18-30 years from Bangalore, India. MATERIALS AND METHODS: Basal recordings of RI
      and SI were determined by Photo Pulse Plethysmography (PPG) picked up from the
      fingertip using BIOPAC system and BFPWV was obtained using Doppler. Recordings
      were obtained at three different time points during the menstrual cycle. Analysis
      was done using repeated measures ANOVA with Bonferroni correction. RESULT: There
      was a significant decrease in above parameters p <0.05 during the mid-cycle.
      Correlation between RI and SI was also significant p<0.05. CONCLUSION: These
      findings suggests that the menstrual cycle affects the arterial stiffness and one
      of the factor is oestrogen. Hence, women are less prone to the incidence of
      cardiovascular diseases before menopause. Screening for arterial stiffness in a
      general population, using these indices is valid, economical and reliable.

PMID- 25386421
TI  - "Is there an Association Between Self-Reported Sleep Duration, Body Mass Index
      and Waist-Hip Ratio in Young Adults? A Cross-Sectional Pilot Study".
AB  - INTRODUCTION: Sleep is vital for mental and physical health of an individual.
      Duration of sleep influences the metabolism and regulates body weight. OBJECTIVE:
      To assess the cross-sectional association of sleep duration with body mass index
      (BMI) and waist-hip ratio in Malaysian students. METHODS: Eighty-nine Malaysian
      students of both genders, and with a mean (standard deviation) age of 21.2 (0.9)
      years were included. Institutional Ethics Committee clearance was obtained prior
      to the start of study. The subjects were interviewed regarding the average hours
      of sleep/day, their self-reported sleep duration was categorized as < 6hour/day
      (short sleep duration), 6-7hour/day and > 7hour/day. Their height (in meters),
      weight (in kilograms), waist and hip circumference (in centimetre) were measured.
      BMI and waist-hip ratio were calculated using appropriate formulas and expressed
      as mean (standard deviation). The duration of sleep was compared with BMI and
      waist-hip ratio using one way ANOVA. RESULTS: No statistical significance was
      observed when sleep duration was associated with BMI (p=0.65) and waist-hip ratio
      (p=0.95). Duration of sleep did not affect BMI and waist hip ratio in the
      Malaysian students in our study. The age and healthy lifestyle of the subjects in
      this study may have been a reason for no significant influence of short sleep
      duration on the BMI and waist-hip ratio. CONCLUSION: No association was found
      between sleep duration with BMI and waist hip ratio in the Malaysian students.

PMID- 25386422
TI  - Effect of isometric handgrip exercise training on resting blood pressure in
      normal healthy adults.
AB  - INTRODUCTION: The aim of the present study was to study the effect of isometric
      handgrip (IHG) exercise training on resting blood pressure in normal healthy
      volunteers. MATERIALS AND METHODS: Hand grip spring dynamometer was used for IHG
      exercise training. A total of 30 normal healthy volunteers in the age group of 20
      40 y were enrolled for the study. Exercise training protocol consisted of five 3
      min bouts of IHG exercise at 30% of maximum voluntary contraction separated by 5
      min rest periods. Exercise was performed 3 times/wk for 10 wk. Subject's blood
      pressure was measured before and after exercise. RESULT: There was a significant
      reduction in resting blood pressure following 10 wk of exercise training. Both
      Systolic and Diastolic blood pressure reduced significantly (p<0.001).
      CONCLUSION: IHG exercise training might be a simple, effective, inexpensive and
      non-pharmacological method in lowering blood pressure.

PMID- 25386423
TI  - Study of Auditory, Visual Reaction Time and Glycemic Control (HBA1C) in Chronic
      Type II Diabetes Mellitus.
AB  - BACKGROUND: Diabetes mellitus is a disease of insulin deficiencyleads to micro
      and macro vascular disorder. Neuropathy is one of the major complication of
      chronic uncontrolled Diabetes affecting the Reaction time. OBJECTIVES: To study
      the correlation between the glycosylated HbA1C and Auditory, visual Reaction time
      in chronic Type II diabetes (40-60y) of on oral hypoglycemic drugs of>10 y
      duration in two groups (n-100 in each group , both Males & females) and compared
      within the study groups and also with the age matched control group (100).
      MATERIALS AND METHODS: HbA1C-Glycosylated HbA1C was measured by Particle enhanced
      immunoturbidimetric test method. Auditory and visual reaction time (ART, VRT)
      were measured by PC 1000 Reaction timer for control & study groups i.e. Group-I -
      Chronic Type II DM for >10 y with HbA1c < 7.0, and Group II - chronic Type-IIDM
      for >10 y with HbA1c > 7.0 ie impaired glycemic control. Exclusion Criteria-
      Subjects with Auditory and visual disturbances, alcoholism and smoking.
      Statistical Analysis - One-way ANOVA. Using SPSS 21 software. RESULT: Both the
      groups had prolonged ART and VRT than controls. Among the study group, G-II (DM
      with HbA1C >7) had increased Auditory & Visual Reaction time than Group I which
      is statistically significant p-value <0.05. CONCLUSION: Impairment of sensory
      motor function of peripheral nervous system is more in chronic diabetic with less
      glycemic control ie., HbA1C>7 who have shown increased Auditory and Visual
      Reaction time than chronic DM with HbA1C<7.Severity of Peripheral neuropathy in
      Type II Diabetics could be due to elevated HbA1C.

PMID- 25386424
TI  - Reaction time in Stroop test in Nepalese Medical Students.
AB  - BACKGROUND: Stroop test is one of the widely used tests in cognitive psychology.
      It is used both in healthy population and also in patients to assess the
      selective attention. The selective attention as assessed by it is also found to
      be altered in bilinguals. In Nepal, most of the students are bilingual since most
      of the courses are in English language. Thus, they learn English language along
      with their native languages. This study is aimed to assess the selective
      attention in healthy Nepalese medical students. OBJECTIVE: To study the reaction
      time in stroop test in medical students of Nepal. MATERIALS AND METHODS: This
      study was conducted on 30 healthy male students aged 23.1+/-2.8 yrs. They were
      asked to read congruent (red printed in red ink) and incongruent (red printed in
      blue ink) tests in classical stroop cards. The reaction times for both the tests
      were calculated. Median with inter-quartile range was obtained for reaction time.
      Wilcoxon's Sign Rank Test was used to compare reaction time and errors between
      congruent and incongruent cards. RESULTS: The subjects took 82.10 (63.75-107.76)
      sec longer to read incongruent stroop test (p<0.001). The error made was 0 in
      congruent stroop test and 1.5 (0-3) in incongruent stroop test (p<0.001). No
      students made error in the congruent test but 60% (18) of students made error in
      incongruent test (p<.001) and interference percentage in incongruent was 157
      (115.32-213.50)%. CONCLUSION: The reaction time and interferences were more in
      incongruent stroop test than congruent test. The interference was very high than
      that of previous literature's value. This indicates that Nepalese students have
      delayed attention while performing classical English version of stroop test.

PMID- 25386425
TI  - Electrocradiographic Qrs Axis, Q Wave and T-wave Changes in 2nd and 3rd Trimester
      of Normal Pregnancy.
AB  - BACKGROUND: Pregnancy although a physiological phenomena affects all the
      functions of the maternal body and brings about remarkable changes in the
      cardiovascular system. The cardiovascular changes and many of the physiological
      adaptations of normal pregnancy alter the physical findings thus, sometimes
      misleading the diagnosis of heart disease. Pregnancy also brings about various
      changes in the electrocardiogram, further confusing with that of heart disease.
      This study is undertaken to highlight the effect of normal pregnancy on the QRS
      axis, Q wave and T-wave of the Electrocardiogram and thereby helps us to
      distinguish it from that of pathological changes. OBJECTIVES: To study the effect
      of normal pregnancy on the QRS axis, Q wave and T-wave in the electrocardiogram
      and to compare with that of normal non pregnant women. MATERIALS AND METHODS:
      Fifty normal pregnant women in 2nd and 3rd trimester each between 20- 35 y of age
      and 50 normal non pregnant women of the same age group were selected for the
      study. A 12 lead ECG was recorded by using ECG machine with special emphasis on
      QRS axis, Q wave and T-wave changes and all the parameters were analysed.
      RESULTS: The ECG changes observed in our study include, deviation of QRS axis
      towards left as pregnancy advanced, significant increased incidence of occurrence
      of prominent Q waves in lead II, III and avF in pregnant group (p < 0.05 ) and, T
      wave abnormalities like flat and inverted T-waves in lead III, V1 - V3 were more
      frequent in pregnant group ( p<0.05 ) than in non pregnant group. CONCLUSION:
      Normal pregnancy brings about various changes in ECG. These changes during
      pregnancy should be interpretated with caution by the physicians. It is necessary
      to understand the normal physiological changes which in turn help us in better
      management of those with cardiac disease.

PMID- 25386426
TI  - Assessment of BMI, Serum Leptin Levels and Lipid Profile in Patients with Skin
      Tags.
AB  - BACKGROUND: Skin tags (ST) are benign lesions composed of loose fibrous tissue,
      associated with obesity and atherogenic profile. Thus help in the follow up by
      considering ST as a useful cutaneous sign for the risk factor of atherosclerosis.
      AIM: To evaluate the association of skin tags with BMI, serum leptin and lipid
      profile. MATERIALS AND METHODS: The study was carried out in 40 cases with ST and
      40 age and gender matched controls. Subjects on oral contraceptives and systemic
      drugs especially lipid lowering agents, pregnant women, cases with medical
      history of endocrine disease, acute infection, erythroderma and psoriasis, cases
      with a drug history of isotretinoin use in last six months were excluded from the
      study. Blood samples were collected. Serum lipids and serum leptin were
      estimated. RESULT: The acrochordons group showed significantly higher values of
      BMI, total cholesterol (TC) and TC/HDL ratio. 60% of the patients with ST were
      overweight and 10% were obese. There was no statistical significant difference in
      leptin levels between the groups. Leptin showed a positive significant
      correlation with BMI in the acrochordons group. CONCLUSION: All the above
      derangements confirm that ST is cutaneous findings frequently associated with
      obesity and dyslipidemia. Thus follow-up of these patients with regard to the
      development of diseases associated with atherosclerosis may be beneficial.

PMID- 25386427
TI  - To ascertain the utility of urinary methyl malonic Acid as a potential marker of
      ischemic heart failure.
AB  - BACKGROUND: Methyl Malonic Acid (MMA) is known to be an integral component of the
      cascade of events in mitochondrial energy metabolism and since heart failure
      involves energy pathways, it is probable that levels of MMA could be used as a
      reliable biomarker to objectively identify the disease during the early stages
      and help in prognostication. MATERIALS AND METHODS: The present study was
      envisaged to evaluate the relation between urinary MMA levels in patients with
      Ischemic heart disease and in those progressing to failure. The relationship
      between the severity of the disease and the level of MMA in urine were also
      evaluated. Analysis of urinary MMA was done by Gas Chromatography-Mass
      Spectrometry (GC-MS) using stable isotope dilution. Twenty patients each with
      Ischemic Heart Disease, heart failure and controls were recruited in this pilot
      study. RESULTS: The mean value of MMA in patients with IHD was 126.71(+/-66.3)
      pmol/L and those with IHF was 390.76 (+/-97.99) pmol/L with the difference being
      statistically significant (p<0.001). Co-existing B12 deficiency was excluded as
      that was a potential confounder. CONCLUSION: Levels of MMA were significantly
      higher in patients with heart failure compared to those with IHF, which were
      significantly higher than controls. Evaluation of the correlation between MMA
      levels and the stage of the disease did not reach statistical significance; but
      this requires adequately powered studies to support this preliminary finding.

PMID- 25386428
TI  - Inherent suppression of thyroid stimulating hormone in newly diagnosed
      dyslipidemic patients - indication for use of thyromimetics?
AB  - BACKGROUND: Dyslipidemia triggers a sequel of metabolic derangements such as
      insulin resistance, hyperglycemia and oxidative stress via vicious cycle.
      Dyslipidemia is characterised by elevation of plasma cholesterol, triglycerides
      (TGs), or both, or a low level of high-density lipoprotein (HDL) which in turn
      can progress to atherosclerosis a forerunner for ischemic heart disease (IHD).
      Dyslipidemia is seen even in subclinical hypothyroid patients. OBJECTIVES: The
      aim of the study was to look for thyroid & glycemic abnormalities in dyslipidemic
      patients and compare it with euthyroid, normolipidemic group. MATERIALS AND
      METHODS: Thirty primarily dyslipidemic patients and 30 euthyroid normolipidemic
      subjects aged 25-55 years were tested for fasting plasma glucose (FPG),
      fructosamine, lipid profile, thyroid hormones - T3, T4 and thyroid stimulating
      hormone (TSH). The values were compared with those of age matched euthyroid
      normolipidemic control group. RESULTS: The dyslipidemic pool showed small but
      significant decrease in the TSH levels with comparable T3, T4 levels as compared
      to euthyroid group. The group also had significantly higher FPG, total
      cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) levels and
      lower high density lipoprotein (HDL) levels as compared to the euthyroid
      normolipidemic group. The plasma fructosamine levels were similar in both the
      groups. The observed results reflected a picture of subclinical hyperthyroidism
      in dyslipidemic patients. CONCLUSION: The observations of the present study
      preclude a need to assess the thyroid status in patients of primary dyslipidemia
      as both conditions per se have an increased risk of cardio vascular diseases. A
      subclinical hyperthyroid state may essentially be helpful in maintaining the
      lipid metabolism. The prevailing mild hyperthyroid status also makes it important
      to reconsider the accuracy of long term glycemic indicators like fructosamine and
      possibly glycated haemoglobin in these patients. Upon establishment of their
      efficacy and safety, thyromimetics may have a role in the treatment of
      dyslipidemia.

PMID- 25386429
TI  - Homocysteine, Paraoxonase-1 and Vascular Endothelial Dysfunction: Omnibus viis
      Romam Pervenitur.
AB  - Increased oxidative stress, alterations of lipid metabolism and induction of
      thrombosis have been suggested to be pathogenic links which are present between
      hyperhomocysteinaemia and atherosclerosis. However, the mechanism by which
      homocysteine (Hcy) can promote atherogenesis is far from clear and it has been
      debated. In the presence of cardiovascular risk factors, endothelial dysfunction
      is the central commodity which converges a plenty of factors, which have been
      named as atherogenic. Now-a-days, there are only few studies which have presented
      the correlation between antioxidant enzyme HDL-associated-paraoxonase 1(PON1) and
      Hcy in atherosclerosis. Both PON 1 and Hcy have been implicated in human diseases
      which are related to endothelial dysfunction. Although paraoxonases have the
      ability to hydrolyze a variety of substrates, only one of them, Hcy-thiolactone,
      is known to occur naturally. It seems very likely that the involvement of Hcy in
      atherosclerotic disease is mediated through its interactions with PON1. 

PMID- 25386430
TI  - Antibiotic resistance in uropathogenic e. Coli strains isolated from non
      hospitalized patients in pakistan.
AB  - PURPOSE: To study multidrug-resistance in Uropathogenic E. Coli (UPEC) isolated
      from non-hospitalized patients. MATERIALS AND METHODS: Altogether, 250 bacterial
      samples were collected from non-hospitalized patients. Their identifications were
      done on basis of Gram-staining, colony morphology, biochemical testing and PCR.
      Susceptibility testing was performed by using standard protocols which were
      recommended by CLSI. STATISTICAL ANALYSIS: For comparisons, statistical analysis
      was performed by using software, Graphpad Prism 5.0 RESULTS: In total, 32% (n =
      80) of the isolates were identified as E. Coli strains and their susceptibility
      patterns for different antibiotics were determined. The data indicated least
      resistance against tazocin [(TZP) -1.25%], amikacin [(AK) -1.8%], tigecycline
      [(TGC)- 2.5%] and nitrofurantoin [(F) -3.75%]. For both minocycline (MH) and
      sulzone (SUL), resistance rate was 5%, for gentamicin (CN), it was 16.25%, while
      higher resistances were observed against cephalothine [(KF)- 70%], cefotaxime
      [(CTX) -58.5%], ceftazidime [(CAZ)- 57.5%], cefepime [(FEP) -55%], cefuroxime and
      cefixime [(CXM) (CFM)- 53.75 %]. Resistance against ciprofloxacin (CIP) was
      57.5%, for norfloxacine (NOR), it was 52.5% and incase of sparfloxacin (SPX), it
      remained 55%. High percentage of the isolates were resistant to cotrimoxazole
      [(SXT) -86%] and Amoxicillin [AMX-CLA (AMC)- 76%]. No resistance against
      meropenem (MEM) was observed. CONCLUSION: Highest level of drug-resistance was
      observed against trimethoprim-sulfamethoxazole (TMP-SMZ) among clinical isolates
      of uropathogenic E. Coli collected from non-hospitalized patients.

PMID- 25386431
TI  - Estimation of Recent Transmission of Mycobacterium Tuberculosis Strains among
      Iranian and Afghan Immigrants: A Cluster-Based Study.
AB  - BACKGROUND: Iran has extended borders with high-TB burden countries (Afghanistan
      and Pakistan) and immigrations of these populations influences TB distribution in
      the region and threatens the control strategies. The aim of this study was to
      evaluate the extent of recent TB transmission among Iranian and Afghan cases.
      MATERIALS AND METHODS: Spoligotyping and 15-locus variable number tandem repeat
      (VNTR) typing were applied to genotype 102 MTB isolates (2009 to 2010).
      Phylogenetic relationships were analysed by two methods: a cluster-graph method
      and a minimum spanning tree (MST) method. Furthermore, evaluation of recent TB
      transmission was assessed with three indices including, RTIn, RTIn-1 and TMI.
      RESULTS: Using molecular typing, 35 different spoligotypes were detected among
      the studied isolates. Seventy seven cases (75.4%) were distributed into 10
      clusters and the remaining 25 (24.5%) isolates had a unique pattern. The cluster
      sizes also ranged from 2 to 21 isolates. The most frequent spoligotype in our
      populations belong to Haarlem (n=30, 29.4%) followed by CAS (n= 29, 28.4%) and
      Beijing (n=16, 15.6%) lineages. The used indices give the following values: RTIn
      = 0.75, RTIn-1 = 0.65 and TMI = 0.24. CONCLUSION: The low rate of TB transmission
      in our findings (24%) showed that the mode of TB transmission in Iran is mostly
      associated with reactivation of a previous TB infection and that recently a
      transmitted disease has a minor role. However, the increasing incidence of the
      intra-community transmission in recent years highlights the need for establishing
      new strategies for control of TB.

PMID- 25386432
TI  - Comparative prevalence of antimicrobial resistance in community-acquired urinary
      tract infection cases from representative States of northern and southern India.
AB  - CONTEXT: Urinary tract infections (UTIs) are amongst the most common infections
      described in outpatient settings. Increased antimicrobial resistance (AMR) of
      urinary tract pathogens is a matter of global public health concern. Treatment of
      UTI depends on both prevalence and antimicrobial resistance (AMR) of causative
      bacteria at any specific geographical location. AIM: This study was undertaken to
      compare the prevalence of uropathogens and their AMR profile in two different
      geographical parts of India. MATERIALS AND METHODS: Clean-catch mid-stream urine
      samples were collected from adult patients, bacterial flora isolated from human
      urine was evaluated for antimicrobial susceptibility profile using Kirby Bauer's
      disc diffusion method among patients from Hyderabad (Southern India), Rajasthan
      and Punjab (Northern India). The data were analysed using Chi-square (chi2) test,
      confidence interval (CI), odds ratio (OR) analysis and p-value using SPSS 16
      software. RESULTS: Escherichia coli (55.1%) were the most prevalent isolates
      followed by Enterococcus faecalis (15.8%). Amikacin was the most active
      antimicrobial agents which showed low resistance rate of 14%. The present study
      revealed the geographical difference in prevalence of uropathogens with
      Klebsiella pneumoniae being the second most common uropathogen followed by E.
      faecalis in the states from northern India while no K. pneumoniae was seen in
      samples from southern India but E. faecalis was the second most prevalent
      organism. CONCLUSION: Therefore, development of regional surveillance programs is
      highly recommended for implementation of national CA-UTI guidelines in Indian
      settings.

PMID- 25386433
TI  - Case report and literature review of carbapenem resistant shewanella putrefaciens
      isolated from ascitic fluid.
AB  - Shewanella species are Gram-negative, non-fermentative, oxidase positive, motile
      bacilli with the major phenotypic characteristic of production of large amounts
      of hydrogen sulfide. Shewanella putrefaciens, primarily considered to be an
      environmental bacterium, is infrequently recovered from clinical specimens.
      Herein, we report a case of ascitic fluid infection with carbapenem resistant
      Shewanella putrefaciens in a patient with underlying liver disorder requiring
      repeated ascitic fluid tapping. Proper antibiotic therapy helped in complete
      recovery of the patient. 

PMID- 25386434
TI  - Morganella morganii causing abscess over the anterior chest wall- a case report.
AB  - A 17-year-old female college student presented with recurrent abscess over the
      anterior chest wall since one and half year. Morganella morganii was isolated
      from the aspirated pus. Patient was started on oral ciprofloxacin and the lesion
      resolved in two weeks. 

PMID- 25386435
TI  - Seroprevalence of Toxoplasma IgG Antibodies in HIV Positive Patients in and
      Around Khammam, Telangana State.

PMID- 25386436
TI  - Role of FNAC in the Preoperative Diagnosis of Salivary Gland Lesions.
AB  - BACKGROUND: The characteristic cytologic features of the common salivary gland
      lesions have been well-delineated in literature. However, there also exist
      cytologic pitfalls and overlapping features that make an accurate diagnosis
      difficult in few cases. The present study was designed to compare the cytologic
      findings of salivary gland lesions with the histologic diagnoses, in order to
      assess the sensitivity, specificity and diagnostic accuracy of FNAC, with an
      emphasis on discordant cases. MATERIALS AND METHODS: Patients with suspected
      salivary gland enlargements, who were referred for FNAC, were included in this
      study, which was done over a 3 year period in a medical college hospital. FNAC
      was performed by using the standard procedure. Smears were stained by using
      Papanicolaou's and MGG stains. Cytologic diagnosis was compared with
      histopathologic diagnosis wherever it was available. RESULTS: Eighty eight
      patients with salivary gland swellings were included in the study. The ages of
      the patients ranged from 15 to 82 years, with the M:F ratio being 1.6:1. Out of
      88 cases, 68 had swellings in parotid gland, 19 had them in submandibular gland
      and one had them in hard palate. Pleomorphic adenoma was the commonest neoplasm
      which was seen in our study. Mucoepidermoid carcinoma (MEC) was the only
      malignant lesion seen in our study. One each of Warthin's tumour (WT) and MEC
      were overdiagnosed and underdiagnosed respectively, the reason being squamous
      metaplasia in WT and subtle nature of malignant cells in low-grade MEC.
      CONCLUSION: WT and MEC can pose problems in cytologicdiagnosis. Sampling errors
      and interpretational errors can lead todiscordant diagnoses.

PMID- 25386437
TI  - Clinicopathological study of prostatic biopsies.
AB  - INTRODUCTION: Prostatism is a common malady in the geriatric age group. Benign
      prostatic hyperplasia and Carcinoma of the prostate are increasingly frequent
      with advancing age. The aim of the present study is to study the spectrum of
      prostatic lesions among the biopsies received in a rural hospital. MATERIALS AND
      METHODS: One hundred and six cases of prostatic biopsies received in the
      Department of Pathology, Rajah Muthiah Medical College and Hospital - Annamalai
      University were included in the present study. There were 44 needle biopsies and
      62 TURP specimens. All the specimens were fixed in 10% neutral buffered formalin
      and 5MU sections were stained with Hematoxylin and Eosin stain (H & E stain).
      Relevant clinical data including age, the presenting complaints and S.PSA values
      in suspected cases of carcinoma prostate were recorded. RESULTS: Among the 106
      biopsies received, 79 (74.52%) cases were of Benign prostatic hyperplasia, two
      cases (1.89%) were Prostatic intraepithelial neoplasia and 25 cases (23.58%) were
      Carcinoma of Prostate. Prostatitis was the most common associated lesion in cases
      of benign prostatic hyperplasia presenting in 25.31% patients. Among the
      Carcinoma patients, 20 cases (80%) were of Adenocarcinoma of prostate and 5 cases
      (20%) were Small cell carcinoma of prostate. Both Benign prostatic hyperplasia
      and Carcinoma prostate were common in the seventh decade. Most common clinical
      presentation was difficulty in micturition. Most common histological type of
      Carcinoma prostate was Adenocarcinoma. Serum PSA estimation was done in 49 cases
      of prostate biopsies. Elevations of serum PSA levels were noted in both BPH and
      Carcinoma prostate patients.Eight cases of BPH, had serum PSA values in the range
      of 0-4ng/ml. Six cases of Carcinoma prostate ,had serum PSA values in the range
      of >80 ng/ml. CONCLUSION: Benign prostatic hyperplasia is the most commonly
      encountered prostatic lesion. Although, investigations like transrectal
      ultrasonogram and serum PSA estimation aids in diagnosis, a definitive diagnosis
      of benign and malignant lesions of prostate can be made by histopathological
      study of prostatic biopsies.

PMID- 25386438
TI  - Case series of skin adnexal tumours.
AB  - BACKGROUND: Skin adnexal tumours (SATs) are a large and diverse group of benign
      and malignant neoplasms. They are uncommon. They can be single or multiple,
      sporadic or familial and they might be markers for syndromes associated with
      internal malignancies. Benign adnexal tumours are more common and malignant SATs
      are rare and are locally aggressive and have the potential for nodal involvement
      and distant metastasis with a poor clinical outcome.Therefore recognition of SATs
      and establishing a diagnosis of malignancy in SATs is important for therapeutic
      and prognostic reasons. AIMS AND OBJECTIVES: SATs are rare benign and malignant
      neoplasms. They are not commonly encountered in the routine surgical pathology
      practice.Hence this study aims at finding the frequency, clinical presentation
      and the histopathological appearances of SATS, and the differentiating features
      between benign and malignant tumours. MATERIALS AND METHODS: This is partly a
      retrospective and partly a prospective study done in a tertiary care hospital
      over a period of four years .All the SATs reported during this period are
      analysed for their clinical features, age, sex incidence and their gross and
      histopathological features. RESULTS: In the four years period 1,64,220 patients
      attended the hospital. The total number of SATS reported during this period were
      21 cases (0.0128 %) Benign tumours were 19 (90.48%). Malignant tumours were
      2(9.52%) The mean age for males 36.9 years and for females 35. Two years. There
      were 11 male patients and 10 female patients. Tumours of hair follicular
      differentiation were 7 (33.33%). Tumour like lesion of sebaceous origin was 1
      (4.76%). Tumours of sweat gland origin were 11 (52.38%). Malignant tumours of
      eccrine origin were 2 (9.52%). CONCLUSION: SATs are not common. Their incidence
      in our study is only 0.0128 % of all cases. Eventhough benign SATs are more
      common than the malignant tumours, malignant SATs can occur both in young and
      elderly patients and they are aggressive and the SATs should be excised with wide
      tumour free margins.

PMID- 25386439
TI  - Associated factors with male infertility: a case control study.
AB  - OBJECTIVE: Sperm analysis is an important step to evaluate and diagnose male's
      infertility. The present study aimed to determine associated factors with males'
      infertility by using semen analysis. MATERIALS AND METHODS: In this study 96 men
      were evaluated who attended to the infertility clinics of Ilam province, western
      Iran between May 2010 to May 2011. Semen analysis was done using the Weili
      Dynamic Sperm Analysis software adapted to the WHO classification. Based on
      movement and speed characters, sperms were classified to either A, B, C or D
      classes. Participants were stratified into two groups that called "Oligospermia
      (OS)" with sperm counts of less than 20 million in mL (n=48) and "Non
      Oligospermia (NOS)" with values more than determined cutoff point (n=48).
      RESULTS: The Mean age +/-SD for OS and NOS group were 29.9 +/-5.1 y and 31.17 +/
      5.24 y, respectively (p>0.05). Overall, 62.5% of OS and 31.2% of NOS were
      clinically infertile (OR=3.6, CI, 1.5-8.5, p=0.01). A significant difference was
      found between job and live ratio(A+B+C) in NOS group (F=2.8, p<0.05). CONCLUSION:
      Prevalence of infertility was higher in the OS men compared to the NOS group. The
      main risk factors in the OS group were History of Varicocele surgery and
      residence site of patients that are totally similar to the NOS men. Further case
      control studies and clinical trials are recommended to recognize infertility
      causes in men.

PMID- 25386440
TI  - A qualitative and quantitative analysis of AgNORs in keratocystic odontogenic
      tumor, unicystic ameloblastoma and multicystic ameloblastoma.
AB  - AIMS: A comparative evaluation of proliferation activity in unicystic
      ameloblastoma (UA), multicystic ameloblastoma (MA) and keratocystic odontogenic
      tumor (KCOT) using silver staining technique. SETTINGS AND DESIGN: In the present
      study 21 histopathologically confirmed paraffin blocks,7 each of UA, MA and KCOT
      were selected and stained with silver nitrate. MATERIALS AND METHODS: For
      quantitative analysis, 100 cells were counted at 1000x magnification for AgNORs
      and the mean value was calculated. Qualitative analysis of AgNORs included normal
      (oval shaped) and abnormal groups (bean shaped) in the lesion. STATISTICAL
      ANALYSIS: The statistical analysis of data was done by a specialist statistician
      using two way ANOVA and multiple comparisons with Tukey's test in advanced excel.
      RESULTS: The AgNOR count was more in KCOT when compared to MA and UA with the
      pattern of distribution of AgNORs more in basal than in the parabasal layer in
      KCOT. The qualitative analysis showed small to large oval AgNOR's in KCOT and few
      clusters in MA whereas in UA irregular clusters were seen. CONCLUSION: This
      concludes the expediency of AgNOR staining in reflecting the high proliferation
      rate and a more aggressive behavior of KCOT in comparison to MA and UA which
      signifies requirement of a more hostile surgical approach in KCOT to avoid
      recurrences following different treatment modalities.

PMID- 25386441
TI  - Cytopathological Pattern of Tubercular Lymphadenopathy on FNAC: Analysis of 550
      Consecutive Cases.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) of lymph nodes is a simple,
      cost effective, out-patient procedure used for diagnosis of various causes of
      lymphadenopathies. In tuberculous lymphadenitis, it not only used for the
      cytological diagnosis but also used for other ancillary testing such as Ziehl-
      Neelsen staining and AFB Culture. AIMS: Our study was designed to evaluate the
      cytopathological pattern of FNAC aspirate of patients presenting with
      lymphadenopathy with special reference to tuberculous lymphadenopathy. MATERIALS
      AND METHODS: In this study all the patients referred to the cytopathology lab for
      FNAC of lymph nodes between January 2011 to June, 2013 were included. Out of 1050
      patients presenting with lymphadenopathies, there were 550 cases of tuberculous
      lymphadenitis. The cytopathological findings of these 550 cases were analyzed.
      RESULTS: A female preponderance was noted in our study with maximum incidence in
      the 3rd decade. Cervical lymph nodes were the most common nodes to be involved.
      Gross examination of aspirate showed maximum cases (74.5.2%) of whitish material.
      Among the four cytological patterns on FNAC, maximum cases demonstrated caseous
      necrotic material with degenerated inflammatory cells. Ziehl- Neelsen staining
      showed overall AFB positivity of 44.54%. Maximum AFB positivity was seen in cases
      having caseous necrosis only. CONCLUSION: FNAC is a simple, cost effective
      technique with high degree of accuracy in diagnosing Tubercular Lymphadenitis.
      Despite certain limitations and pitfalls, FNAC coupled with Ziehl- Neelson
      staining should be the 1st line investigation in cases with lymphadenopaty, in a
      developing country with high prevalence rate of tuberculosis.

PMID- 25386442
TI  - Haematological characterisation and molecular basis of asian Indian inversion
      deletions delta Beta thalassemia: a case report.
AB  - The hereditary persistence of fetal hemoglobin (HPFH) and delta beta thalassemia
      are heterogeneous disorders characterised by increased levels of fetal hemoglobin
      and high level of this Hb continues in adulthood. The distinction between these
      two conditions is not always possible with routine hematologic analysis and
      molecular characterisation of the defect is required. We encountered such a rare
      case of delta beta thalassemia in a 10-year-old male child who presented with
      features of thalassemia intermedia. Hemoglobin analysis showed 100% HbF while
      molecular analysis revealed Asian Indian inversion-deletion GgammaAgamma(delta
      beta) zero thalassemia. 

PMID- 25386443
TI  - Malignant adenomyoepithelioma of breast masquerading as soft tissue lytic lesion
      of right iliac bone: a rare entity.
AB  - Adenomyoepithelioma (AME) of breast is a low grade malignant biphasic tumour,
      usually seen in elderly women as a firm, well circumscribed tumour having both
      glandular and myoepithelial cells. The cells may show atypical features. The
      tumour may harbour foci of carcinoma which may be epithelial type, myoepithelial
      type, both or of metaplastic cells. The behaviour is hard to predict as it can be
      treated by local excision, recurrence is known or it can present with distant
      metastasis and hence the prognosis. We present a case of 50-year-old women who
      presented with right iliac bone lytic lesion diagnosed as metastatic deposits.
      Past history revealed that patient was diagnosed and treated for AME of right
      breast seven years back. The metastatic deposits also showed features of
      adenomyoepithelioma. Hence, a diagnosis of malignant AME deposits in right iliac
      bone was made. 

PMID- 25386444
TI  - Insulinoma: a comprehensive summary of two cases.
AB  - Pancreatic endocrine tumours are rare in occurrence. They may present with a
      baffling range of symptoms which pose a diagnostic dilemma. Two cases of
      pancreatic insulinoma are presented herewith. Both presented with neuro
      psychiatric complaints and were treated symptomatically for depression, anxiety,
      seizures etc. The diagnosis in these patients was missed for years. Insulinoma
      being a great diagnostic challenge, requires reasonably high clinical suspicion,
      accurate biochemical diagnosis and radiological localization to avoid extensive
      surgery. The aim is to highlight the occurrence of this rare tumour at a tertiary
      care hospital. 

PMID- 25386445
TI  - Primary laryngeal neuroendocrine carcinoma - a rare entity with deviant clinical
      presentation.
AB  - Primary laryngeal neuroendocrine carcinomas are rare neoplasms. WHO classifies
      them under five categories of which, the moderately differentiated neuroendocrine
      carcinoma is synonymous with atypical or malignant carcinoid tumour. We report a
      rare case of primary laryngeal neuroendocrine carcinoma with an unusual and
      misleading clinical presentation. The initial cytological diagnosis of secondary
      neuroendocrine carcinoma in the cervical lymph node led to the suspicion of
      primary neuroendocrine carcinoma in the larynx. 

PMID- 25386446
TI  - Tracheobronchial amyloidosis-a series of two cases.
AB  - Amyloidosis is a rare disorder characterised by accumulation of insoluble
      fibrillar proteins in extracellular space. Respiratory amyloidosis presents as
      two tracheobronchial forms (local and diffuse) and two parenchymal forms (nodular
      and diffuse), of which diffuse tracheobronchial amyloidosis is the least common.
      We herein present two cases of tracheobronchial amyloidosis. 

PMID- 25386447
TI  - Adrenal cortex heterotopia in an undescended testis-a case report.
AB  - Heterotopic adrenal cortex is usually found in the kidney, retroperitoneum and
      spermatic cord. It is common among pediatric age group and rarely encountered in
      adults. Our case presented with swelling in the right inguinal region with on and
      off dragging pain. On clinical examination testis was absent in the right scotal
      sac which was confirmed with ultrasonogram. The clinical diagnosis was right side
      undescended testis. Orchidectomy was performed and on microscopic examination we
      incidentally found out an ectopic adrenal cortical rest in the rete testis with
      atropic changes in the testis. Though the ectopic adrenal tissue was indolent in
      our case, literature suggests that it can undergo transformations like
      hyperplasia, adenoma and carcinoma, leading to undesirable complications. We
      present this case for the rarity at this age and site, and for the awareness that
      it may cause complications if left untreated. 

PMID- 25386448
TI  - Koch's Disease Presenting as an Isolated Testicular Mass- An Unusual Occurance.
AB  - Isolated testicular tuberculosis (TB) is rarely seen. A 72-year-old, farmer
      presented with complaints of discharging sinus from scrotum along with pain and
      swelling. The patient had no sign of tuberculosis. On examination a hard mass
      arising from the left testis was noted along with a discharging fistula on the
      overlying scrotal skin. Chest x-ray and ultrasound examination of the abdomen
      were within normal limits. After assessing the testicular mass, an informed
      consent was taken thereafter left orchiectomy and fistulectomy performed.
      Histopathological examination revealed caseating granulomas along with numerous
      Langhan's giant cells consistent with tuberculous orchitis. The patient received
      anti-TB treatment for six months. The rare involvement of testis by tuberculosis
      needs to be mentioned. 

PMID- 25386449
TI  - Haemoglobin s interaction with Beta thalassaemia- a case report from assam,
      India.
AB  - Interaction of Hb S with beta thalassaemia is being reported here as this type of
      case is rare. Hb S (beta6 glu->val) is a genetic disorder which occurs due to
      beta globin gene mutation of haemoglobin. In India, the Hb S is prevalent in the
      central part, in the eastern, western and southern tribal belt regions and among
      the tea tribe communities of Assam. The Hb S carriers (Sickle cell trait) leads a
      normal life but the Sickle cell disease patients show certain clinical
      manifestation like joint pain, anaemia and jaundice. The HPLC report of the
      patient showed Compound heterozygous for Hb S- beta thalassaemia. The complete
      blood count was measured in automated haematology analyser. Mutational pattern of
      the beta thalassaemia as well as the presence of Hb S gene was detected by PCR.
      The case showed severe clinical manifestations and transfusion was required due
      to inheritance of the IVS 1-5 G ->C beta- thalassaemia mutation with the Hb S
      gene. 

PMID- 25386450
TI  - "Comparative efficacy of different doses of fentanyl on cardiovascular responses
      to laryngoscopy and tracheal intubation".
AB  - BACKGROUND: This study was conducted to determine an effective bolus dose of
      fentanyl, which would attenuate the cardiovascular response to laryngoscopy and
      tracheal intubation. MATERIALS AND METHODS: A randomised double blind controlled
      study was carried out on 50 healthy adult patients (ASA I and II) undergoing
      elective surgery under general anaesthesia. The patients were randomly allocated
      into two groups of 25 each i.e. group A and group B receiving fentanyl 3 MUg/kg,
      5 MUg/kg intravenously three minutes before intubation respectively. The pulse
      rate, systolic blood pressure was recorded at induction, during intubation and at
      1,3, 5 min post intubation. RESULTS: The study showed that both the doses were
      equally effective in blunting the pulse rate response, but the 5MUg /kg proved
      significantly effective in blunting the blood pressure response. The rate
      pressure product, a measure of cardiac O2 consumption was found to be
      significantly lower in fentanyl 5MUg/kg compared to fentanyl 3MUg/kg. CONCLUSION:
      So, we conclude that both blood pressure and rate pressure product were
      completely abolished by a bolus dose of fentanyl 5MUg /kg in comparison with
      fentanyl 3MUg/kg following laryngoscopy and intubation.

PMID- 25386451
TI  - Comparison of dexmedetomidine, propofol and midazolam for short-term sedation in
      postoperatively mechanically ventilated neurosurgical patients.
AB  - BACKGROUND: Effective management of analgesia and sedation in the intensive care
      unit depends on the needs of the patient, subjective and/or objective measurement
      and drug titration to achieve specific endpoints. AIM: The present study compared
      the efficacy of dexmedetomidine, propofol and midazolam for sedation in
      neurosurgical patients for postoperative mechanical ventilation. MATERIALS AND
      METHODS: Ninety patients aged 20-65 years, ASA physical status I to III,
      undergoing neurosurgery and requiring postoperative ventilation were included.
      The patients were randomly divided into three groups of 30 each. Group D received
      dexmedetomidine 1 mcg/kg over 15 minutes as a loading dose, followed by 0.4-0.7
      mcg/kg/h. Group P received propofol 1 mg/kg over 15 minutes as a loading dose,
      followed by 1-3 mg/kg/h. Group M received midazolam 0.04 mg/kg over 15 minutes as
      a loading dose, followed by 0.08 mg/kg/h. MEASUREMENTS: Heart rate, mean arterial
      pressure, sedation level, fentanyl requirement, ventilation and extubation time
      were recorded. RESULTS: Adequate sedation level was achieved with all three
      agents. Dexmedetomidine group required less fentanyl for postoperative analgesia.
      In group D there was a decrease in HR after dexmedetomidine infusion (p<0.05),
      but there was no significant difference in HR between group P and group M. After
      administration of study drug there was a significant decrease in MAP comparison
      to baseline value in all groups at all time intervals (p<0.05), except
      postextubation period (p>0.05). Extubation time was lowest in group P (p<0.05).
      CONCLUSION: Dexmedetomidine is safer and equally effective agent compared to
      propofol and midazolam for sedation of neurosurgical mechanically ventilated
      patients with good hemodynamic stability and extubation time as rapid as
      propofol. Dexmedetomidine also reduced postoperative fentanyl requirements.

PMID- 25386452
TI  - Laparoscopic Adrenalectomy in a Patient of Von Hippel Lindau Syndrome with
      Ventriculo-Peritoneal Shunt-Anaesthetic management.
AB  - Von Hippel Lindau (VHL) syndrome has a predilection to manifest multiple
      haemangioblastomas in the retina and central nervous system. We report a rare
      case of raised intracranial pressure during bilateral laparoscopic adrenalectomy
      for pheochromocytoma in a patient of VHL syndrome who had a ventriculoperitoneal
      shunt. 

PMID- 25386453
TI  - Comparative study of efficacy of oral ivermectin versus some topical antiscabies
      drugs in the treatment of scabies.
AB  - BACKGROUND: The conventionally used topical antiscabetics have poor compliance.
      Ivermectin, an oral antiparasitic drug, has been shown to be an effective
      scabicide and could be a useful substitute. This study was designed to compare
      efficacy of oral ivermectin with commonly used topical antiscabies drugs.
      MATERIALS AND METHODS: This study was conducted on four groups including 60
      patients in each group by simple random sampling. Treatment given in each group
      was: Group 1: Ivermectin (200 MUg/kg body weight) oral in a single dose, Group 2:
      Topical Permethrin 5% cream single application, Group 3: Topical gamma benzene
      hexachloride (GBHC) lotion 1% single application and Group 4: Topical Benzyl
      benzoate (BB) lotion 25% single application. All of the patients were followed
      for improvement in terms of severity of disease and severity of pruritus at the
      end of 1(st) wk and 6(th) wk. RESULTS: Efficacy of ivermectin, permethrin, GBHC
      and BB lotion considering improvement in severity of pruritus as parameter were
      85%, 90%, 75% and 68.33% respectively at 2(nd) follow-up. Similarly considering
      improvement in severity of lesion as parameter, results were 80%, 88.33%, 71.66%
      and 65% respectively at 2(nd) follow up. Topical Permethrin (5%) was more
      effective as compared to topical BB lotion and topical GBHC lotion (p<0.05,
      significant) but statistical difference between efficacy of topical Permethrin
      and oral Ivermectin was non-significant (p>0.05). CONCLUSION: The results
      suggested that oral Ivermectin and topical Permethrin (5%) were equally
      efficacious. Oral Ivermectin is well tolerated, non irritant to skin, does not
      show central nervous system side effects because it does not cross blood brain
      barrier. So, the good therapeutic response with few side effects seen with oral
      Ivermectin can be useful in those patients for whom topical treatment is
      potentially irritant and less well-tolerated.

PMID- 25386454
TI  - Evaluation of antioxidative and antidiabetic activity of bark of holarrhena
      pubescens wall.
AB  - OBJECTIVE: The objectives of the study are to screen out various phytochemicals
      and to evaluate the antioxidant and antidiabetic potential of the stem bark of
      Holarrhena pubescens Wall (Holarrhena antidysenterica). MATERIALS AND METHODS:
      The antioxidant activity was determined by the DPPH (2,2-diphenyl-1
      picrylhydrazyl) radical scavenging activity where ascorbic acid was taken as
      positive control. The antioxidant property was later exploited and the methanolic
      extract of plant was tested for antihyperglycemic activity in glucose overloaded
      hyperglycemic mice. The extract was tested for its hypoglycemic activity at two
      dose levels, 250 and 500 mg/kg respectively where Glipizide 5 mg/kg was taken as
      standard reference drug. All results are presented as mean +/- SD (Standard
      Deviation). Significant differences between experimental groups were determined
      by Student's t-test. RESULTS: The methanolic and water extract showed strong
      antioxidant activity with inhibition of more than 90% DPPH free radicals at the
      concentration of 100MUg/mL. The hypoglycemic activity of methanolic extract on
      glucose tolerance test were significant (p <0.05) for the effects of 500 mg/kg
      after 120 min of treatment and (p <0.01) for 250 mg/kg of extract after half hour
      of treatment compared to control. CONCLUSION: The presence of flavonoides,
      phenolic compounds suggested that they may be partially responsible for
      antioxidant and antidiabetic activity.

PMID- 25386455
TI  - Comparison of topical anti- fungal agents sertaconazole and clotrimazole in the
      treatment of tinea corporis-an observational study.
AB  - OBJECTIVES: To compare the efficacy of topical antifungal agents, Sertaconazole
      and Clotrimazole in Tinea corporis patients. MATERIALS AND METHODS: A total of
      60(n=60) patients were included in the study. They were divided into two groups
      of 30 patients each. First group included patients treated with topical
      Sertaconazole as test drug whereas the second group constituted patients treated
      with topical Clotrimazole as standard drug. The patients were advised to apply
      the drug on affected area twice daily for three weeks. The parameters like
      erythema, scaling, itching, margins and size of the lesion and KOH mount were
      taken for the assessment of efficacy. This was an open labelled study and
      patients were followed up every week for three weeks. RESULTS: The total score
      included all grades in erythema, itching, scaling, margins and size of lesion and
      KOH mount. There was significant reduction in erythema (p<0.02) and highly
      significant reduction in scaling (p<0.001), itching (p<0.001) and margins of
      lesion (p<0.001) among Sertaconazole group. The mean difference and the standard
      deviation of total scores for Clotrimazole were 7.20 and 1.69 and for
      Sertaconazole group 8.80 and 1.52 respectively. The p-value on application of
      students unpaired t- test was p<0.001 (Highly significant). CONCLUSION: From the
      present study, it can be concluded that topical Sertaconazole shows better
      improvement in the clinical parameters than topical Clotrimazole within a span of
      three weeks in the treatment of T corporis.

PMID- 25386456
TI  - Comparing the efficacy and influence on the quality of life of three classes of
      drugs used in bronchial asthma - a prospective study.
AB  - OBJECTIVES: To compare the efficacy of formoterol, montelukast and acebrophylline
      when used in combination with budesonide in patients with bronchial asthma and to
      determine their role in the improvement of the quality of life of patients.
      MATERIALS AND METHODS: A total of 75 patients were divided into 3 groups based on
      treatment given - formoterol 6 mcg/puff + budesonide 100 mcg/puff combination
      inhaler, 2 puffs twice daily; oral montelukast 10 mg once daily + budesonide 100
      mcg/puff, 2 puffs twice daily and oral acebrophylline 100 mg twice daily +
      budesonide 100 mcg/puff, 2 puffs twice daily. The patients were followed-up for 4
      wk after initiating treatment. Spirometry values - forced expiratory volume in 1
      second (FEV1) and peak expiratory flow rate (PEFR), before and after treatment
      were recorded. The quality of life was assessed before and after treatment using
      Asthma Quality of Life Questionnaire (AQLQ). Analysis was done using repeated
      measures ANOVA followed by Bonferroni's post-hoc test. RESULTS: As compared to
      baseline values, FEV1, PEFR and Quality of Life showed significant improvement in
      all 3 groups after 4 wk of treatment (p-value < 0.01). Three patients in
      acebrophylline-treated group reported gastric irritation while no adverse effects
      were reported in the other groups. CONCLUSION: Formoterol, montelukast or
      acebrophylline combined with inhaled corticosteroids have similar efficacy in the
      treatment of asthma.

PMID- 25386457
TI  - Can Metabotropic Glutamate Receptor 7 (mGluR 7) be a Novel Target for Analgesia?
AB  - INTRODUCTION: The present study was carried out to study the role of metabotropic
      glutamate receptor 7 (mGluR7) using its agonist, N,N'-bis(diphenylmethyl)-1,
      ethanediamine (AMN082) for nociceptive stimuli, in animal models. By conducting
      this research, we aim to introduce a novel target for acute pain management.
      OBJECTIVE: To study the role of metabotropic glutamate receptor 7 (mGluR7), in
      analgesia, using mGluR7 agonist AMN082 in animal models. MATERIALS AND METHODS:
      Swiss albino mice of either sex, weighing 20-30gm were used for the study. The
      animals were divided into 3 groups with 6 mice in each group: Control or Normal
      group received 0.5% methylcellulose in normal saline; Standard group received the
      drug tramadol HCl at 40mg/kg; and test group received drug AMN 082 at 5mg/kg. All
      the drugs were administered by intraperitoneal route. Hot plate test and Tail
      flick test were done to evaluate the analgesic effect of the drug. Reaction time
      for the end points in both the models were noted before drug administration at 0
      min and after drug administration at 15, 30,60,90 and 120 min. Statistical
      analysis was done using One-Way-ANOVA followed by Tukeys post hoc test. p-value
      was considered significant at <= 0.05. RESULTS: The group that received AMN082
      showed significantly lesser reaction time compared to normal and standard groups
      in both the analgesia models. CONCLUSION: The mGluR 7 stimulation by an agonist
      AMN082, did not show analgesic effect but induced hyperalgesia in response to
      thermal nociceptive stimuli.

PMID- 25386458
TI  - Anti hypertensive prescribing patterns and cost analysis for primary
      hypertension: a retrospective study.
AB  - OBJECTIVE: The present study was conducted to analyze the current prescription
      pattern and cost analysis of antihypertensive drugs in hypertensive patients in a
      tertiary care hospital. MATERIALS AND METHODS: A retrospective cross-sectional
      study was conducted in tertiary care hospital, Bangalore for three months and
      utilized 300 prescriptions for the analysis. The data analysed from the
      prescription included patients demographics, stage of hypertension according to
      JNC VII guidelines, type of drug therapy, class of anti-hypertensive, and cost
      effectiveness of therapy. Drug acquisition costs was calculated, using the cost
      of the cheapest available drug and the most commonly prescribed dosage, for each
      drug on a daily and annual basis. Total annual drug expenditure on buying
      required doses of all antihypertensive prescribed in the study population for a
      year was calculated. RESULTS: Monotherapy (48.94%) was leading trends of
      antihypertensive therapy followed by fixed dose combination (35.04%) and
      polytherapy (16.01%). The most frequent antihypertensive class to be prescribed
      were CCBs (38.59%) followed by beta blockers (24.07%). The ranking in terms of
      cost utilized per year from the highest to the lowest found in this study was:
      alpha blockers> ACE-inhibitors> ARBs> CCBs> beta blockers > diuretics. The
      diuretics were most cost-effective (Cost per day: 5.89 +/- 2.87; Cost per year:
      2129.02 +/- 1080.49) in relation to the other antihypertensive prescribed.

PMID- 25386459
TI  - First Indian study evaluating role of biochemical investigations and diagnostic
      tools in detection of adverse drug reactions.
AB  - AIM OF STUDY: To evaluate the role of biochemical investigations (BI) and
      diagnostic tools (DT) in ADR detection. MATERIALS AND METHODS: An observational
      prospective cross-sectional study was done using suspected ADR data collection
      form. RESULTS: A total of 2381 ADR related events were recorded in two years.
      Total number/percentage of biochemical abnormalities (BA) related ADR detection
      rate was 14.57% and of DT was 1.091% in contrast to 84.33% recorded with clinical
      presentation. Maximum cases were inward patients (87.13%), 67.02% were recorded
      by active surveillance. ADR detection rate at one point & detection on follow up
      was 56.31% Vs 46.38%. ADR detection rate of ECG, endoscopy, X-ray were 0.57%,
      0.22%, 0.22% and of CT scan, MRI, DEXA scan, USG and biopsy was 0.04% each.
      Maximum ADRs were severe/serious, latent and Type-A in nature. Anemia (4.6%),
      followed by liver dysfunction (2.8%), renal dysfunction, electrolyte imbalance,
      hyperglycemia (1.1% each), abnormal coagulation profile (1%), decrease platelet
      count (0.8%), hypoglycemia (0.7%) were the most common BAs. Anti retroviral drugs
      (ART), tirofiban and methotrexate accounted for anemia, ART and anti tubercular
      drugs for liver & renal dysfunction, insulin for hypoglycemia, tirofiban,
      paclitaxel, capecipabine and ifosfamide for thrombocytopenia, hematuria by
      enoxaparin & dyslipidemia with ART were common ADRs. CONCLUSION: BI and DT can
      play very important role in ADR detection.

PMID- 25386460
TI  - Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV
      Patient - A Case Report.
AB  - The most important and unique adverse effect of abacavir (ABC) is fatal
      hypersensitivity reaction (HSR). The objective of this report is to describe a
      case of ABC induced HSR that occurred in an Indian HIV patient during treatment.
      Although this adverse effect is not uncommon, it is perhaps underreported or has
      never been reported so far in an Indian case scenario. A 44-year-old known case
      of HIV-1 was admitted in view of his worsening condition and very low CD4 cell
      counts 3 cells/MUL. He was on anti-retroviral therapy since three years but not
      regular. On the basis of treatment failure, non-compliance and progressive low
      CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/
      ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular
      rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3
      4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of
      the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse
      reaction. We did confirm ABC induced HSR by de-challenge wherein, rash
      disappeared within 2-3 days and LFT came back to normal within 5 days. However,
      no rechallenge was done. HSR was more in favour of ABC because atazanavir failed
      to produce any similar reaction after re-challenge. 

PMID- 25386461
TI  - Zolpidem induced hyponatremia: a case report.
AB  - Zolpidem is a non-benzodiazepine hypnotic that acts by binding to (GABAA)
      receptor. This is a case report of a patient with chronic insomnia for which he
      had initially been receiving benzodiazepine hypnotic alprazolam and for the past
      three years, he had switched himself to non-benzodiazepine hypnotic, zolpidem and
      had progressively increased the dose to 20 mg. The patient presented with history
      of drowsiness, nausea and vomiting of short duration. Investigations revealed
      that the patient had hyponatremia. Decreased serum sodium, elevated urine sodium
      with normal urine osmolarity was detected. Therefore, we report this as a case of
      drug induced syndrome of inappropriate antidiuretic hormone (SIADH) as other
      likely causes were ruled out by appropriate investigations. The causality
      assessment was done according to the WHO scale and found to be "Probable". 

PMID- 25386462
TI  - Evaluation of antinociceptive activity of aqueous extract of bark of psidium
      guajava in albino rats and albino mice.
AB  - BACKGROUND: Psidium guajava is commonly known as guava. Psidium guajava is a
      medium sized tree belonging to the family Myrtaceae found throughout the tropics.
      All the parts of the plant, the leaves, followed by the fruits, bark and the
      roots are used in traditional medicine. The traditional uses of the plant are
      Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity,
      Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory,
      Analgesic and Antinociceptive effects. AIM: To evaluate the antinociceptive
      activity of aqueous extract of bark of Psidium guajava in albino rats with that
      of control and standard analgesic drugs aspirin and tramadol. MATERIALS AND
      METHODS: Mechanical (Tail clip method) and thermal (Tail flick method using
      Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were
      used to evaluate the extract antinociceptive activity. Six groups of animals,
      each consists of 10 animals, first one as control, second and third as standard
      drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the
      extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the
      respective test. RESULTS: The results obtained demonstrated that aqueous extract
      of bark of Psidium guajava produced significant antinociceptive response in all
      the mechanical and thermal-induced nociception models. CONCLUSION: AEPG
      antinociceptive activity involves activation of the peripheral and central
      mechanisms.

PMID- 25386463
TI  - Socio-demographic and other risk factors of pre eclampsia at a tertiary care
      hospital, karnataka: case control study.
AB  - BACKGROUND: Pre-eclampsia is one of the leading causes of maternal and infant
      morbidity and mortality worldwide. The aetiopathogenesis of this condition
      involves combination of genetic predisposition and environmental factors. The aim
      of the study was to determine the socio demographic and other risk factors of pre
      eclampsia. MATERIALS AND METHODS: A case control study was conducted at a
      tertiary care hospital, Karnataka among 100 cases of pre-eclampsia and 200
      controls without pre eclampsia. Non probability purposive sampling technique was
      adopted to select the study subjects. Data was collected by using a pre tested
      semi structured questionnaire which included information related to socio
      demographic and other known risk factors of pre eclampsia. Primary data was
      collected by interviewing study subjects and secondary data of cases was obtained
      from case records. Data was analysed using SPSS. RESULTS: Study subjects included
      100 cases and 200 controls. Age of less than 20 y (OR=3.8), monthly income of
      less than Rs4000 (OR=6.8), age of menarche of less than 12 y (OR=13.1), family
      h/o pre eclampsia (OR=36.0), family h/o Diabetes (OR=44.9), family h/o
      hypertension (OR=16.7) and previous h/o PIH (OR=58.5) are found to be significant
      risk factors of pre eclampsia. CONCLUSION: The significant risk factors may be
      used for screening pre-eclampsia during registration of pregnancy.

PMID- 25386464
TI  - Complications associated with blood donations in a blood bank at an Indian
      tertiary care hospital.
AB  - BACKGROUND: Blood donation, though safe, has a few potentially avoidable
      complications associated with it. They are important reasons for the failure of
      the donors to return for repeat donations. The aim of this study was to assess
      the frequency and identify the possible factors associated with increased risk of
      blood donation related complications so that they can be minimized. MATERIALS AND
      METHODS: A prospective study was done over a period of four months in the blood
      bank of an Indian tertiary care hospital to record the donation related
      complications. RESULTS: Out of 7450 blood donations, total donation associated
      complications were 74, of which majority were vasovagal reactions (VVRs) (n=48),
      followed by venous hematomas (n=24) and arterial punctures (n=2). The incidence
      of VVRs was more, though not statistically significant, in females,
      replacement/repeat donors, donors between 21-30 y of age and who had a body-mass
      index (BMI) of 18.5-24.9. VVRs were more common in April (p=0.002) and in those
      who donated 450ml of blood (p<0.001). Though hematomas were more frequent in
      females, voluntary donors, donors in age-group of 41-50, those with BMI<18.5 and
      in those who donated 350ml of blood, statistically significant association was
      seen only in repeat donors (p<0.001). CONCLUSION: Our study emphasizes that blood
      donation in our country has a complication rate of nearly 1%.

PMID- 25386465
TI  - Prevalence of Osteoarthritis of Knee Among Elderly Persons in Urban Slums Using
      American College of Rheumatology (ACR) Criteria.
AB  - BACKGROUND: The prevalence of osteoarthritis among elderly is high and it majorly
      affects the quality of life. Knee osteoarthritis is the most common form of
      osteoarthritis. Timely diagnosis using clinical criteria and effective
      intervention is of utmost importance. AIM: To estimate the prevalence and
      determinants of osteoarthritis of knee joint among elderly persons residing in an
      urban slum of Delhi using ACR clinical criteria. MATERIALS AND METHODS: We did a
      community-based cross-sectional study among 496 elderly (>= 60 years) persons
      residing in urban slum of Delhi, India from December 2009 to February 2010. The
      American College of Rheumatology (ACR) criteria was used to clinically diagnose
      osteoarthritis knee. STATISTICAL ANALYSIS: Bivariate analysis using Chi-square
      test and multivariate analysis was done to identify the determinants. Sensitivity
      and specificity of individual factors to diagnose osteoarthritis knee was
      calculated. RESULTS: The prevalence of osteoarthritis was estimated to be 41.1%
      (95% C.I., 36.7-45.6). Female sex and age >= 70 y were found to be independent
      risk factor for osteoarthritis knee. Among those having knee pain, presence of
      crepitus and tenderness were the most sensitive factors whereas bone overgrowth
      and bone warmth were most specific factors. CONCLUSION: The prevalence of
      osteoarthritis knee was high among this elderly population and increased with
      age. Overall, individual factors of ACR criteria were both sensitive and specific
      in diagnosing osteoarthritis knee. In resource constrained setting of urban
      India, it can be an effective tool in clinical diagnosis of osteoarthritis knee.

PMID- 25386466
TI  - Conducting record review studies in clinical practice.
AB  - Clinical record review or chart review is a previously recorded data to answer
      clinical queries. Such a study can be used to answer specific clinical questions
      in a relatively easy and less resource intensive manner. But these studies may be
      constrained by the limited information retrievable and inadequacy of records.
      Various types of data sources may be available for conducting such reviews (like
      case charts, computerized registries, etc), each with specific strengths and
      weaknesses. The procedure usually consists of drawing up the research question,
      identifying the appropriate data source, devising a data extraction plan,
      extracting the data, checking for errors, data analysis, and appropriate
      archiving and dissemination of the findings. The ethical aspects in such studies
      primarily pertain to issues of informed consent and confidentiality. This paper
      provides a broad overview of how to go about a clinical record review, and serves
      as a ready reference for those who would like to undertake such record reviews. 

PMID- 25386467
TI  - Impact of amitryptiline on migraine disability assessment score.
AB  - AIM: Migraine headache is a common disorder, several drugs have been tried as a
      prophylaxis to reduce the attacks of headache. AIM of this study is to see the
      impact of amitriptyline on quality of life in migraneurs using Migraine
      Disability Assessment Score. MATERIALS AND METHODS: In this study 300 patients of
      either gender who required prophylaxis for migraine without aura were selected.
      The patients were of the age group 18-60 years. The MIDAS questionnaire was
      administered to patients before starting treatment and again after 45 days
      prophylaxis. The improvement was noted. STATISTICAL ANALYSIS: It is a prospective
      study where the severity of symptoms and 'quality of life' in patients is
      assessed before and after treatment using mean, frequency, standard deviation and
      paired't' test. RESULTS: A total of 300 patients were subjected to migraine
      prophylaxis with amiptriptyline. The study showed female preponderance. The mean
      MIDAS score before and after treatment with amitriptyline was 11.6 and 9.4
      respectively. The student't' test showed p-value of <0.005 which was significant.
      CONCLUSION: Migraine prophylaxis with amitriptyline for a period of 45 days
      decreased the severity of symptoms and also reduction in days of migraine
      attacks. However the long term effects on quality of life could not be assessed.
      The study needs to be conducted in a large scale to evaluate the consistency and
      accuracy of the test.

PMID- 25386468
TI  - Alterations in cochlear function after exposure to short term broad band noise
      assessed by otoacoustic emissions.
AB  - BACKGROUND: Sudden or chronic exposure to sound alters the functioning of
      cochlea. This results in temporary or permanent alteration of functioning of
      cochlear cells. Alteration of functioning of outer hair cells (OHC) of cochlea
      following exposure to noise can be assessed by measurement of transient
      otoacoustic emissions (TEOAE). Such a measurement is of great clinical importance
      in early detection of the damage to the OHC. AIM: In this study we aim to study
      effect of noise on outer hair cell function by studying the changes in TEOAE's
      amplitude following exposure to short term broad band noise in healthy
      volunteers. MATERIALS AND METHODS: Twenty volunteers' ten males and ten females
      participated in the study. They underwent pure tone and impedance audiometry to
      rule out ear pathology. Then pre-exposure TEOAE's were recorded. After that they
      were exposed to broad band noise for two minutes. After gap of five minutes again
      TEOAE's were recorded. Pre and post exposure amplitude of TEOAE's was analysed
      statistically.s RESULTS: There was statistically significant difference between
      pre exposure and post-exposure amplitude of TEOAE's. Pre and post exposure values
      for A & B amplitudes showed p-value of 0.0001 whereas values for A-B amplitude
      showed p-value of 0.0001. CONCLUSION: Measurement of TEOAE's can detect early
      changes in the functioning of outer hair cells which cannot be picked by routine
      pure tone audiometry. Thus they can be used in assessing early changes in
      cochlear function following exposure to noise in individuals exposed to sudden
      noise or working in noisy environments. Thus preventive methods to reduce the
      noise induced hearing loss in such individuals can be implemented.

PMID- 25386469
TI  - The efficacy of thermotherapy and cryotherapy on pain relief in patients with
      acute low back pain, a clinical trial study.
AB  - INTRODUCTION: Acute low back pain is one of the most common health problems
      especially in industrialized countries where 75 per cent of the population
      develop it at least once during their life. This study examined the efficacy of
      thermotherapy and cryotherapy, alongside a routine pharmacologic treatment, on
      pain relief in patients with acute low back pain referring an orthopedic clinic
      in Shahrekord, Iran. MATERIALS AND METHODS: This clinical trial study was
      conducted on 87 patients randomly assigned to three (thermotherapy and
      cryotherapy as intervention, and naproxen as control) groups of 29 each. The
      first (thermotherapy) group underwent treatment with hot water bag and naproxen,
      the second (cryotherapy) group was treated with ice and naproxen, and the
      naproxen group was only treated with naproxen, all for one week. All patients
      were examined on 0, 3(rd), 8(th), and 15(th) day after the first visit and the
      data gathered by McGill Pain Questionnaire. The data were analyzed by SPSS
      software using paired t-test, ANOVA, and chi-square. RESULTS: In this study, mean
      age of the patients was 34.48 (20-50) years and 51.72 per cent were female.
      Thermotherapy patients reported significantly less pain compared to cryotherapy
      and control (p<=0.05). In thermotherapy and cryotherapy groups, mean pain in the
      first visit was 12.70+/-3.7 and 12.06+/-2.6, and on the 15(th) day after
      intervention 0.75+/-0.37 and 2.20+/-2.12, respectively. CONCLUSION: The results
      indicated that the application of thermo-therapy and cryotherapy accompanied with
      a pharmacologic treatment could relieve pain in the patients with acute low back
      pain.

PMID- 25386470
TI  - Comparative Study of: Non-Invasive Conservative Treatments with Local Steroid
      Injection in the Management of Planter Fasciitis.
AB  - BACKGROUND: Planter Fasciitis is an annoying and painful condition that limits
      function. There is pain and tenderness in the sole of the foot, mostly under the
      heel, with standing or walking and is considered a self limiting condition.
      Symptoms resolve in 80% to 90% of cases within ten months. However, this long
      interval is frustrating for both patients and clinicians. AIM: This study was
      undertaken to compare the two different modalities of non operative treatment:
      Non- invasive conservative methods: NSAID's, Soft Insoles, Stretching, Ultrasound
      therapy and Contrast baths versus local Steroid injection therapy. MATERIALS AND
      METHODS: Patients by random sampling were divided in two groups. Group A as:
      Conservative group and Group B as Local Steroid Injections group, 100 patients in
      each. Patients were assessed as per Visual Analogue Scale (VAS) at the start of
      treatment and then after 4 wk and 8 wk duration on follow up. STATISTICAL
      ANALYSIS USED: SPSS for Windows (version 10.0) by the Chi-Square test. RESULTS:
      The difference in the distribution of subjects belonging to either of the
      treatment modalities regarding the treatment outcome at four and eight week was
      found to be statistically insignificant. CONCLUSION: As both treatment modalities
      are at par on comparison of their treatment outcome it is better to go for
      conservative approach because this can save the patients from the complications
      of steroid therapy.

PMID- 25386471
TI  - FATCO Syndrome Variant - Fibular Hypoplasia, Tibial Campomelia and
      Oligosyndactyly -- A Case Report.
AB  - The word aplasia/hypoplasia is used for partial or total absence of a bone.
      Fibula, a lower limb bone is one of the most common to be involved with this and
      its incidence is amongst the highest in long bone deficiencies. FATCO syndrome
      consisting of fibular aplasia, tibial campomelia and oligosyndactyly has been
      described in the literature but only one has been reported from India as per our
      literature review. However, it is important to know multiple regional involvement
      can occur along with this syndrome and prove to be a major difficulty for the
      child and the parents both. Due to the rarity of reports on this rare syndrome
      and difficulty in treatment it is important that each such case should be
      described to make the management easier. 

PMID- 25386472
TI  - Prognostic significance of a multimarker strategy of biomarkers in acute heart
      failure.
AB  - BACKGROUND: Heart failure (HF) is a growing public health problem. Patients often
      present to emergency department (ED) with acute onset dyspnea where a rapid
      triage is required to avoid misdiagnosis and to institute appropriate therapy. An
      objective risk-stratification in the ED is warranted to identify patients at high
      risk of adverse outcomes, so that more intensive therapy and vigilant follow-up
      after discharge are instituted. METHODS AND RESULTS: Fifty two consecutive acute
      HF (AHF) patients in NYHA class III/IV were enrolled for the present study. N
      terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac
      troponin T (hsTropT), high-sensitivity C-reactive protein (hsCRP) and Uric acid
      (UA) were evaluated at admission; a second sample for NT-proBNP and hsTropT was
      obtained 48h later. The end-point of the study, a composite of cardiovascular
      death, rehospitalisation for worsening HF symptoms and refractory HF was reached
      in 32.7% of patients during a median follow-up of 4.8mnth. Although, hsTropT
      (>0.014ng/ml), hsCRP (>0.5mg/dl) and UA (>5.6mg/dl for females and >7 mg/dl for
      males) were elevated in the vast majority of patients (92.3%, 75% and 63.5%
      respectively), baseline and changing patterns of NT-proBNP following treatment
      were the only predictors of adverse outcomes on follow-up. A significant
      correlation between hsTropT, hsCRP and UA was observed suggesting a link between
      inflammation, myocyte injury and oxidative stress in AHF. CONCLUSION: Baseline
      and changing patterns of NT-proBNP predicted adverse outcomes on follow-up
      suggesting that a strategy of serial measurement of NT-proBNP could prove
      invaluable in early risk stratification. Further research is needed to understand
      the link between inflammation, myocyte injury and oxidative stress in AHF which
      could provide potential therapeutic targets.

PMID- 25386473
TI  - Comparitive angiographic profile in diabetic and non-diabetic patients with acute
      coronary syndrome.
AB  - BACKGROUND: Cardiac adversity is by far the commonest cause of mortality in
      patients with diabetes. Cardiac involvement in diabetes commonly manifest as
      coronary artery disease (CAD). Definitive diagnosis,precise assessment and
      anatomic severity of CAD requires invasive diagnostic modality like coronary
      angiography. AIMS AND OBJECTIVES: To study angiographic extents, type of vessels,
      number of vessels, severity involving coronary artery and its branches in
      patients with acute coronary syndrome(ACS).Compare the same in diabetics and non
      diabetics with ACS. MATERIALS AND METHODS: Hundred patients with ACS,50 diabetics
      and 50 nondiabetics admitted in Bapuji Hospital ICCU attached to J.J.M. Medical
      College were selected randomly during a period of approximately one and half
      years formed the study group. RBS, FBS was done in all 100 pateints, HbA1c in all
      diabetics. All subjects with ACS were taken up for coronary angiography.
      STATISTICAL ANALYSIS: Chi-square test was used to determine any significant
      difference between two groups. p-value of less than 0.05 was considered
      significant. RESULTS: In our study 22 (44%) out of 50 diabetic patients had
      triple or multi-vessel disease compared to 8 (16%) out of 50 non diabetics.
      Hundred patients with ACS, number of vessels involved were 199, of which 61.3% in
      diabetics and 38.6% in non diabetics, 23(46%) of 50 diabetic patients required
      CABG as treatment outcome. HbA1c levels of >8.5%, 69.2% had triple / multi vessel
      disease and 19 (73.1%) of 23 patients who had to undergo CABG had HbA1c levels
      >8.5%, 24% of diabetics were in third decade, 40% were in fourth decade as
      compared to 10% and 26% of non-diabetics of similar age group. INTERPRETATION AND
      CONCLUSION: This study showed that ACS in diabetic patients presented much
      earlier in life, the severity and extent of CAD and incidence of triple/multi
      vessel disease was significantly high in diabetics when compared to nondiabetics
      with ACS. Diabetics with high HbA1c had more number of coronary vessel
      involvement and the mode of treatment required in them was CABG.

PMID- 25386474
TI  - The Effect of Acebrophylline vs Sustained Release Theophylline in Patients of
      COPD- A Comparative Study.
AB  - INTRODUCTION: Over the past several decades, the use of drug therapy in COPD has
      expanded, and provides an optimistic picture. Methyixanthines are used freely in
      COPD. Of them, Theophylline is an age old bronchodilator and anti-inflammatory
      agent while Acebrophylline is a newer one. Both are used as add on therapy in
      management of stable COPD patients on LAMA (long acting muscarinic antagonists
      like Tiotropium) in present day respiratory practice. This study was designed to
      compare the efficacy as well as tolerability/side-effects of these two drugs at
      recommended doses. MATERIALS AND METHODS: An open randomized comparative
      longitudinal study was conducted on 40 moderate degree COPD patients over a
      period of one year. The patients were randomized into Group-1:receiving
      Acebrophylline 100mg twice daily and Group-2: receiving sustained release (SR)
      Theophylline 300mg once daily orally, in addition to 18MUgm Tiotropium inhalation
      per day through metered dose inhaler. Spirometric variables, symptomatic benefit
      and adverse effects were recorded on three visits (day '0', '21' and '42'). All
      the data were analyzed by SPSS version 17. RESULTS: A comparable clinical
      improvement of symptoms score and spirometric parameters with both the drugs has
      been observed (p-value>0.05). Amount of sputum, frequency of use of reliever
      medication and dyspnoea showed improvement with both the drugs but cardiovascular
      side effects are less with Acebrophylline. CONCLUSION: This study reaffirms the
      rationale of use of Methylxanthines as add on therapy with LAMA in COPD
      management and cardiac safety level with Acebrophylline was considerable.

PMID- 25386475
TI  - Multiple splenic artery aneurysms: a rare cause of extrahepatic portal
      hypertension and massive splenomegaly.
AB  - A 39-year-old nulliparous female was admitted with massive splenomegaly. Computed
      tomography of abdomen revealed multiple aneurysms in the distal half of the
      splenic artery. Splenic artery aneurysms are rare in nulliparous women and most
      cases are reported in females with a past history of pregnancy. Splenic artery
      aneurysms, though very rare are clinically significant as they have a high
      propensity for fatal rupture. Here, we report a patient with multiple splenic
      artery aneurysms presenting as extrahepatic portal hypertension and massive
      splenomegaly. 

PMID- 25386476
TI  - Symmetrical peripheral gangrene following snake bite.
AB  - SPG (Symmetrical peripheral gangrene) is defined as symmetrical distal ischemic
      damage at two or more sites in the absence of large vessels obstruction. It has
      been ascribed to a number of infectious and non infectious conditions including
      connective tissue, cardiovascular, neoplastic and iatrogenic causes. We report a
      unique case of SPG in a 35-year-old Indian female who developed spontaneous
      gangrene of the distal phalanges of the right and left index, middle, ring and
      little fingers and the distal phalanges of all toes of the right and left foot
      following a snake bite. There have been very few cases of peripheral gangrene and
      acute renal failure associated with snake bite in literature. 

PMID- 25386477
TI  - Pseudohypoparathyroidism.

PMID- 25386478
TI  - Poor Tolerance of Motor Cortex rTMS in Chronic Migraine.
AB  - BACKGROUND: Two small studies had evaluated the efficacy of rTMS in migraine. One
      tested high frequency rTMS over the dorsolateral prefrontal cortex while the
      other evaluated 1 Hz rTMS over the vertex. AIM: To test the feasibility of 10 Hz
      rTMS of motor cortex as an adjunctive therapy in patients with chronic migraine
      Materials and Methods: We randomized (2:1 ratio) chronic migraine patients on
      medical preventive treatment to receive either rTMS or sham therapy for 10
      sessions. rTMS (80% resting motor threshold, 10Hz, 20 trains, 5 secs/train, inter
      train interval 1 min, total 1000 stimuli/session) was applied over the right
      motor cortex. RESULT: Nine patients were randomized. Six received rTMS and three
      had sham therapy. Three patients in the rTMS arm withdrew from the study due to
      increased headache frequency and discomfort from the treatment. The remaining six
      cases (3 rTMS, 3 sham) completed the study. The study was prematurely stopped due
      to the significant worsening of headache from rTMS. No significant differences in
      outcome measures were found between real and sham rTMS. CONCLUSION: Although the
      study was terminated prematurely, the high dropout rate (50%) due to worsening
      headaches suggested that rTMS over the motor cortex is poorly tolerated in
      chronic migraine.

PMID- 25386479
TI  - Primary Supratentorial Haemorrhage - Surgery or no Surgery in an Indian Setup.
AB  - INTRODUCTION: Rise of hypertension among younger age group has increased the
      prevalence of intracranial haemorrhage. Conflicting reviews regarding the mode of
      treatment has been a concern to the treating physicians especially in a
      developing country like India. This study was undertaken to underline the
      importance of management and propose a local protocol for primary supra-tentorial
      haemorrhage. MATERIALS AND METHODS: Patients presenting with primary
      supratentorial (ST) haemorrhage fulfilling inclusion criteria are included in the
      study. Decompression craniotomy done in all the patients and the patient
      particulars noted. The primary outcome of death is correlated with various
      particulars and statistical analysis done with SPSS version 16. RESULTS: Mean age
      of presentation was 54.2 years, ranging from 38-71years. Male comprised 82.1% (23
      patients). Seven out of eight patients with Glasgow coma scale (GCS) <=7 (87.5%)
      expired whereas only 3 out of 20 (15%) patients with GCS >7 expired. 50% of the
      patients with intracranial haemorrhage (ICH) in temporo-pari et al., (2/4) or in
      basal ganglia with cortical extension (5/10) expired whereas the mortality in
      cases of ICH in parietal lobe and frontal lobes were 25% (1/4) and 20% (2/10)
      respectively. Clot volume <=100ml had a mortality of 19% (4/21) whereas the
      mortality was as high as 85.7% (6/7) with clot volume >100ml. CONCLUSION:
      Emergency Craniotomy and Evacuation of the Hematoma could be a feasible option in
      between 40 ml to 100ml of Primary ST ICH without intra-ventricular extension. In
      cases of intra-ventricular extension of haematoma surgery is less helpful.
      Midline shift of 5 mm or more might be a poor prognostic factor.

PMID- 25386480
TI  - Embryonal/Fetal subtype hepatoblastoma: a case report.
AB  - Hepatoblastoma is the most common primary liver tumor of childhood and after
      neuroblastoma and nephroblastoma the third most common abdominal neoplasm in this
      age group. Hepatoblastoma is an embryonal tumor classified by histology as
      epithelial (including pure fetal subtype, mixed embryonal/fetal subtype,
      macrotrabecular subtype and small cell undifferentiated subtype), mixed
      epithelial and mesenchymal type (with teratoid and non-teratoid features) and
      hepatoblastoma not otherwise specified. We present a case of a five-months old
      girl with embryonal/fetal subtype hepatoblastoma. The clinical presentation was
      asymptomatic abdominal mass. Ultrasound and MRI scan demonstrated a solid hepatic
      tumor. She presented thrombocytosis and serum alpha-fetoprotein was increased. A
      left lobe hepatectomy was performed and the pathological examination revealed
      complete excision of a mixed embryonalfetal subtype hepatoblastoma. 

PMID- 25386481
TI  - Tandem rhomboid flap repair: a new technique in treatment of extensive pilonidal
      disease of the natal cleft.
AB  - Pilonidal sinus is an annoying chronic benign disease causing disability in young
      adults, mainly affecting the intergluteal furrow. Treatment of this condition
      remains controversial and is represented by a myriad of techniques available.
      Most of the techniques are judged against open excision and secondary healing in
      terms of minimizing disease recurrence and patient discomfort. More recently
      superiority of flap reconstruction to non-flap techniques is accepted. An ideal
      operation should be simple, associated with minimal pain and wound care after
      surgery, minimize hospital stay and have a low recurrence rate. We hereby present
      a new type of rhomboid flap technique for an extensive pilonidal sinus disease.
      This technique has given good results in our hands considering the aforementioned
      factors of an ideal operation. The following case report is of our first stint
      with the procedure. 

PMID- 25386482
TI  - Acute Abdomen Due to Penicillium marneffei: An Indicator of HIV Infection in
      Manipur State.
AB  - Opportunistic infection in HIV disease often present to clinicians in an atypical
      manner testing clinical acumen. Here, we report a case of Penicilliosis marneffei
      (PM) infection presenting to surgical emergency as acute abdomen with undiagnosed
      HIV status in advanced AIDS, chief complaints being prolonged fever and diffuse
      abdominal pain. Radiologic imaging showed non-specific mesenteric and
      retroperitoneal lymphadenopathy. Fine needle aspiration cytology (FNAC) of the
      lymph node was done and subjected to direct microscopy, gram staining and culture
      on Sabouraud's dextrose agar (SDA) which showed Penicillium marneffei. He was
      then treated with intravenous amphotericin. This case is reported for its rarity
      and unusual presentation to sensitise clinicians and microbiologists to consider
      PM as an aetiology in acute abdomen in high risk individuals, more so, in
      patients from north-east India. 

PMID- 25386483
TI  - Giant inguinoscrotal hernia repaired by lichtensteins technique without loss of
      domain -a case report.
AB  - Giant inguinal hernia is a formidable surgical problem. It is defined as inguinal
      hernia extending up to mid thigh or below in standing position. Giant inguinal
      hernia is usually associated with compromised quality of life due to sexual
      discomfort and constant weight bearing. It is a challenge for the operating
      surgeon since it is rare. It may require multistage repair with recurrence being
      common. A 45-year-old male patient presented with Giant inguinal hernia and
      compromised quality of life due to pain and sexual discomfort. Lichtenstein's
      polypropylene mesh repair was done after reducing the sac contents (omentum and
      transverse colon) with partial omentectomy. There was no loss of intra-abdominal
      domain. Postoperative period was uneventful. In literature many techniques are
      available to increase the intra-abdominal cavity (a) Creating progressive
      preoperative pneumoperitoneum (b) Creation of ventral wall defect (c) surgical
      debulking of hernia contents. Recurrence is prevented by reconstruction of the
      abdominal wall using Marlex mesh and a Tensor fasciae lata flap. Laparoscopic
      repair is associated with more recurrence. Lichtenstein's technique is one of the
      preferred treatments. 

PMID- 25386484
TI  - Clinical Outcome of Postplacental Copper T 380A Insertion in Women Delivering by
      Caesarean Section.
AB  - INTRODUCTION: Short interconception period after caesarean section and its
      associated risk of increased morbidity, mortality and surgical interventions
      could be avoided by postplacental IUCD insertion during the procedure. Despite
      the safety reports on intracaesarean IUCD insertion, obstetricians are still
      hesitant to extend the benefit of this long acting reversible contraception to
      women undergoing operative delivery. OBJECTIVE: To study the clinical outcome
      (safety, efficacy, expulsion and continuation rates) of postplacental Copper T
      380A insertion in primiparous women undergoing caesarean section. MATERIALS AND
      METHODS: This study was a prospective observational study, carried out in the
      Department of Obstetrics and Gynaecology, Safdarjung hospital, which is a
      tertiary care hospital of Northern India. Primiparous women who delivered by
      caesarean section over a period of six months (July 2012 to December 2012),
      willing for postplacental intracaesarean IUCD insertion, and willing to comply
      with the study protocol, were recruited for the study. All these subjects
      fulfilled the WHO Standard Medical Criteria for PPIUCD insertion; follow up
      visits were scheduled at 1, 3, 6 and 12 months. RESULTS: A total of 300
      primiparous women underwent postpartum intracaesarean insertion of Copper T 380A.
      The mean age of women included in the study was 23.12 +/- 2.42 years. Most common
      postinsertion complication observed in the immediate postoperative period was
      febrile morbidity (2%). Majority of women (94.33%) had hospital stay of less than
      4 days. The common adverse events observed during follow-up of 12 months were
      menstrual complaints, excessive vaginal discharge and persistent pelvic pain. At
      the end of one year, there were 16 expulsions, 21 removals, and 2 pregnancies
      with gross cumulative expulsion, removal, failure and continuation rates of
      5.33%, 7%, 0.67% and 91%, respectively. CONCLUSION: Postplacental intracaesarean
      Copper T 380A insertion in primiparous women is a safe and effective method of
      reversible contraception, with low expulsion and high continuation rates.

PMID- 25386485
TI  - The utility of caesarean myomectomy as a safe procedure: a retrospective analysis
      of 21 cases with review of literature.
AB  - BACKGROUND: Myomectomy at the time of caesarean delivery has been discouraged
      because of the risk of intractable haemorrhage and increased postoperative
      morbidity. The aim of this study is to determine the safety and feasibility of
      caesarean myomectomy. MATERIALS AND METHODS: A retrospective case control study
      done between June 2012 to May 2013 in a tertiary care teaching hospital in
      Karnataka, India which included 21 pregnant women with uterine fibroids who
      underwent myomectomy during caesarean section and were compared with 42 matched
      controls without uterine fibroids who had caesarean section alone during the same
      period. Primary outcome measures studied were incidence of haemorrhage and need
      for blood transfusion. Secondary outcome measures were duration of operation,
      length of hospital stay, postpartum fever and wound infection. Statistical
      analysis is done using IBMSPSS 20.0 software and students t-test. For calculation
      of incidence of haemorrhage Fisher's exact test is used. RESULTS: Mean age of the
      21 cases was 31.81yrs and 47.62% were primigravida. Total 37 fibroids were
      removed. Subserosal were 30 cases(81.08%) while 1(2.07%) was submucous.
      21(56.76%)fibroids were situated in fundal region and 3(8.11%) were in lower
      segment. Mean change in the haemoglobin from preoperative to postoperative period
      in the cases was 1.3gm/dl(+/-1.155mg/dl) and control was 1.05% (+/-.854mg/dl).
      Two of the cases(9.52%) required blood transfusion compared to none in control.
      None in either group required hysterectomy. Mean duration of surgery was 68.57min
      (+/-15.012min)and 51.55min (+/-9.595min) for controls which is statistically
      significant. CONCLUSION: This study shows that myomectomy during caesarean
      section is a safe procedure and is not associated with major intraoperative and
      postoperative complications.

PMID- 25386486
TI  - Analysis of sexual assault survivours in a tertiary care hospital in delhi: a
      retrospective analysis.
AB  - INTRODUCTION: Rape and abuse of women are common occurrences, which, many a times
      go unspoken due to social stigma or fear of retribution. Rape is a crime not
      against a single human being but against the entire humanity. For granting
      justice to the rape survivor it becomes necessary that such matters are properly
      presented before the Courts of Law. Healthcare workers play an important role in
      this regard because they are the first person who examine the rape victims. They
      prepare a documented record of medical condition of rape victim and do relevant
      sample collection. AIM: The objective of this study is to analyse demographic and
      event characteristics of rape victims who presented to the Emergency Department
      in tertiary care, Delhi after sexual assault. MATERIALS AND METHODS: Data was
      retrospectively collected from the medico legal register of the Department of
      Obstetrics and Gynecology between June 2010 to December 2013. RESULT: We noted a
      marked increase in the number of cases. Mean age of victims was 17 and most
      belonged to the lower socio-economic strata of the society. Use of sedatives and
      physical trauma was not common. Victims often knew the perpetrator of the event.
      Most (58%) of them reported within one day of the incident. Major degrees of
      perineal tears were seen in young victims. CONCLUSION: By understanding the
      demography of the sexual assault victims, we need to train our doctors for proper
      evidence collection not just in a government set up but also in private clinics,
      to help rape victims get justice and proper medical treatment.

PMID- 25386487
TI  - Are we missing hypertrophic cardiomyopathy in pregnancy? Experience of a tertiary
      care hospital.
AB  - BACKGROUND: Controversies persist regarding risks associated with pregnancy and
      delivery in women with hypertrophic cardiomyopathy (HCM). To date, pregnancy
      outcome data for these patients is scarce. We report the experience of
      pregnancies with HCM in a tertiary care hospital. MATERIALS AND METHODS: Data
      regarding cardiac illness and obstetric profile of all women attending the cardio
      obstetrics clinic from January 1990 to December 2012 were studied. The records of
      cardiac illness of all women were checked and all patients with HCM were included
      in the study. RESULTS: Out of total 2016 patients booked in the cardio-obstetrics
      clinic between 1990 and 2012, only 4 women were found to have a diagnosis of HCM
      (0.2%). Of these, 2 women with left ventricular outflow tract obstruction and one
      with non-obstructive HCM had only mild symptoms and tolerated pregnancy and
      labour well. One patient had HCM with restrictive physiology developed heart
      failure and intra-uterine fetal death. CONCLUSION: HCM is underdiagnosed and
      rarely identified in pregnancy. Most patients with HCM tolerated pregnancy well,
      howeverone patient with restrictive physiology developed heart failure during her
      first pregnancy.

PMID- 25386488
TI  - Is surgical intervention for ectopic pregnancy in a low resource set-up
      avoidable?
AB  - BACKGROUND: Ectopic pregnancy is one of the most common life threatening
      complications in the first trimester of pregnancy having significant adverse
      effects on future pregnancy outcome, particularly if salpingectomy is used as the
      modality of treatment. So medical management is now advocated. For that, cases
      need to be diagnosed at an earlier stage. Keeping these backgrounds in mind we
      took up this study to look into the feasibility of conservative management- both
      medical and surgical - in a tertiary care centre. AIMS: To find out the
      demographic profile and risk factors of the ectopic pregnancy cases; the clinical
      presentation of the cases; the mode of treatment offered to the patients.
      MATERIALS AND METHODS: It was a record based retrospective study.All the patients
      diagnosed as ectopic pregnancy in a tertiary care hospital from January, 2011 to
      December, 2012, was included in the study. RESULTS: A total of 234 ectopic cases
      (1.5% of total deliveries) were recorded, constituting 5.4% of total
      gynaecological emergencies of this institute. Majority of patients were
      multigravida (74.4%) and of age group of 26-30years (35.9%). Fallopian tube was
      the most common site (99.1%) with only two cases in ovary. Ampulla (71.4%) was
      found to be most frequent site for implantation in fallopian tube. Pelvic
      inflammatory diseases (38.5%) and past history of induced abortion (35.9%) were
      major risk factors. Most patients (63.3%) did not use any contraceptives and
      30.3% patients used OCP intermittently. No patient presented before 4weeks of
      gestation, while 69.2% presented between 4-7weeks and the rest beyond 7week. They
      presented with shock in 44.9% cases. Surgical treatment was offered in 98.3%
      cases, while medical treatment was offered to only four cases. CONCLUSION: There
      is a huge surgical burden due to ectopic pregnancy impinging on our hospital
      resources. Surgery is resorted to indiscriminately for even those cases that
      could have been medically treated otherwise. Hence, the need to change the
      mindset of the care-providers at all levels to opt for medical management of
      ectopic pregnancy wherever applicable.

PMID- 25386489
TI  - Knowledge, attitude and practice of emergency contraception on nursing personnel.
AB  - INTRODUCTION: Emergency Contraception is a grossly underu-tilized option of
      prevention of pregnancy. It is a safe and effective method which can prevent
      unintended pregnancies, unsafe abortions and unwanted childbirth. Knowledge and
      attitude of Nursing personnel who are both service providers and health educators
      to the community can influence the contraceptive behavior of the people exposed
      to them. A few studies done in our country indicate that their awareness
      regarding EC is low. AIM: To explore the knowledge, attitude and practice of EC
      amongst Nursing Personnel in a medical college hospital. MATERIALS AND METHODS:
      In this study, 185 nursing personnel participated. A predesigned, pretested
      questionnaire was used to collect their responses regarding knowledge, attitude
      and practice of EC. Descriptive analysis of data was done. Results : Out of the
      total, 52.43% of the participants had good knowledge regarding the general
      information of EC, 51.35% had positive attitude towards EC, 47.56% had expressed
      willingness to use EC if indicated whereas only 22.7% had ever used EC. 72.97%
      had expressed willingness to attend awareness programmes on EC. Conclusion :Even
      though knowledge and attitude towards EC among the participants was marginally
      good they had many misconceptions regarding specific aspects like mode of action,
      indications and timing of administration. More awareness programmes would
      definitely clear their misconceptions and apprehensions and encourage Nursing
      Personnel to personally use and promote EC to others.

PMID- 25386490
TI  - Diagnosis of asymptomatic bacteriuria and associated risk factors among pregnant
      women in mangalore, karnataka, India.
AB  - BACKGROUND: Asymptomatic bacteriuria (AB) is common inwomen and increases in
      prevalence with age or sexual activity. Prompt detection and treatment of this
      condition and associated factors decreases complications like acute
      pyleonephritis, intrauterine growth retardation and preterm labour. Chromogenic
      media is a versatile tool in rapid primary screening of the causative organisms
      considerably reducing daily routine workload. AIM: To determine the prevalence of
      AB among pregnant women in a tertiary care set-up and analyse the contributory
      risk factors, its effects on pregnancy and the role of chromogenic media in the
      laboratory diagnosis of these cases. MATERIALS AND METHODS: Urine samples of all
      pregnant women attending pre-natal check-ups with no genitourinary complaints,
      history of fever or antibiotic intake were collected for Gram stain, culture and
      antibiotic sensitivity tests. A second urine specimen for culture and sensitivity
      testing was obtained from those with significant bacteriuria. The results were
      compared with patients showing negative urine cultures. RESULTS: The overall
      prevalence of this clinical condition in our study was 13.2%. The significant
      isolates were Klebsiella pneumonia and E.coli and the most common risk factor was
      a previous history of urinary tract infection. The isolates were easily
      identified by using chromogenic agar ( HiCrome ) but colonies of uncommon
      pathogens like Acinetobacter and Streptococcus species appeared white and needed
      further identification. CONCLUSION: Screening of pregnant women for AB at first
      prenatal checkup helps analyse the associated factors and prevents its effects on
      pregnancy. The use of a chromogenic media can enhance reporting accuracy and will
      be an effective tool to monitor these cases routinely.

PMID- 25386491
TI  - Application of bethesda system for cervical cytology in unhealthy cervix.
AB  - INTRODUCTION: Women presenting with unhealthy cervix needs to be evaluated with
      Papanicolaou (Pap) smear for epithelial abnormalities. AIM: To detect epithelial
      cell abnormalities in unhealthy cervix using the 2001Bethesda system of reporting
      for cervical cytology and to confirm histopathologicaly the findings of Pap
      smear. MATERIALS AND METHODS: In this study, 125 women with clinical diagnosis of
      unhealthy cervix underwent conventional cytology. Cervical biopsies were taken
      from abnormal areas seen on colposcopy and sent for histopathology. RESULTS: Out
      of 125 Pap smears, 122 were satisfactory for evaluation (19 normal, 86 negative
      for intraepithelial lesion or malignancy and 17 with epithelial cell abnormality)
      and 3 were unsatisfactory (one hemorrhagic and two severe inflammation). Out of
      17 (13.60%) cases with epithelial cell abnormality, ASC-US was seen in 6 (4.80%),
      LSIL in 7 (5.60%), HSIL in 1 (0.80%), squamous cell carcinoma in 1 (0.80%), AGC
      endocervical in 1 (0.80%) and adenocarcinoma in 1 (0.80%) patients. Cervical
      biopsy was taken in 67 women. Diagnostic accuracy of Pap smear for preinvasive
      and invasive disease was 81.15% with overall sensitivity and specificity 78.57%
      and 88.67% respectively and predictive value of 64.71%. CONCLUSION: Women with
      clinical diagnosis of unhealthy cervix should be evaluated by cytology to detect
      any premalignant or malignant lesions. The Bethesda system for cervical cytology
      reporting should be used universally as it will give a standardized
      interpretation.

PMID- 25386492
TI  - Is low dose vaginal misoprostol better than dinoprostone gel for induction of
      labor: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy and safety profile of low dose vaginal
      misoprostol with dinoprostone gel for induction of labor in term pregnancies.
      METHODS: The study was conducted at Lady Hardinge Medical College and Smt Sucheta
      Kriplani Hospital on 100 pregnant women with term pregnancy after application of
      inclusion and exclusion criteria. The women were randomized in 2 groups of 50
      women each. Group I received misoprostol 25MUg at every six hour vaginally for a
      maximum of five doses for induction of labor; while group II received
      dinoprostone gel 0.5 mg every six hourly for a maximum of three doses. Maternal
      outcomes such as mode of delivery and induction delivery interval; and fetal
      outcomes such as APGAR score and incidence of NICU admission were assessed in
      both the groups. Statistical analysis was done using student t-test and chi
      square test. RESULTS: There was no significant difference in the mean induction
      to delivery interval in both the groups (14.32+/-0.13 hours in Group I and
      14.92+/-0.18 hours in Group II, p=0.75), mode of delivery, indication of cesarean
      section and perinatal outcome. However, significant difference was observed in
      requirement of oxytocin augmentation in both the groups (32% in Group I and 68%
      in Group II, p=0.005). CONCLUSION: Vaginal misoprostol in low doses is similar in
      efficacy and safety to dinoprostone gel for cervical ripening and labor induction
      in term pregnancy.

PMID- 25386493
TI  - Non puerperal uterine inversion in a young female- a case report.
AB  - We report a case of 28-year-old, primipara who presented with complaints of mass
      descending per vaginum along with excessive bleeding and foul smelling vaginal
      discharge for the past six months. Clinical examination revealed an inverted
      uterus, cervix and vagina with a large submucosal fundal fibroid. A diagnosis of
      non-puerperal uterine inversion was made. Surgical management included vaginal
      myomectomy with repositioning of the uterus using an abdomino-vaginal approach
      and a successful outcome. Histopathology confirmed the diagnosis of leiomyoma.
      Hence, we conclude that uterus-sparing surgery should be considered in young
      females desirous for future pregnancy until the final pathology is known. 

PMID- 25386494
TI  - Perforated duodenal ulcer -a rare cause of acute abdomen in pregnancy.
AB  - Acute abdomen during pregnancy is a medico-surgical emergency demanding
      concerted, synchronized specialties approach of obstetrician, surgeon and
      gastroenterologist. Duodenal perforation is one of the rarer causes of acute
      abdomen in pregnancy. Here, we report a case of duodenal perforation with
      peritonitis in third trimester of pregnancy requiring surgical management. Our
      aim of reporting this case is to stress the physicians to keep the differential
      of duodenal perforation also in mind while dealing with cases of acute abdomen in
      pregnancy and to proceed with multidisciplinary approach for better feto-maternal
      outcome. 

PMID- 25386495
TI  - Plasma D-dimer as a Prognostic Marker in ICU Admitted Egyptian Children with
      Traumatic Brain Injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a leading cause of morbidity and
      mortality in children. This study aimed at evaluation of the D-dimer blood levels
      as a new marker to predict prognosis and outcome of traumatic brain injuries
      among children. MATERIALS AND METHODS: This case control study was conducted at
      the Paediatric Intensive Care Unit (ICU), Alharm Hospital in Giza, Egypt during
      2012-2013, on 46 Paediatric cases admitted to ICU with head injury and 20 normal
      age-matched controls. Clinical data and venous blood samples were prospectively
      collected at 1(st), 3(rd) and 14(th) day of admission, in addition to examination
      finding as Glasgow coma scale (GCS), cranial brain computed tomography (CT),
      routine laboratory investigations (CBC, CRP, SGOT, SGPT, urea, creatinine, random
      blood glucose, Na, K and arterial blood gases) plasma D-dimer, INR, PT, aPTT and
      PC. Data analysis was carried out accordingly and ROC curve was performed to
      explore the discriminating ability of D-dimer through estimation of its accuracy
      in differentiating temporal survivorship of those with TBI. RESULTS: Cases were
      classified according to outcome into survivors and non-survivors. Significant
      difference was observed between cases and controls and between survivors and non
      survivors during 1(st), 3(rd) and 14(th) day of the follow up including GCS,
      blood levels of D-dimer, PT and aPTT. ROC curve analysis for D-dimer showed
      decline in both sensitivity from 89.5% to 73.7% and specificity from 100% to
      81.5% along the study days respectively. D-dimer time measurements showed
      significant decline among survivors from 4.2 to 0.7, while in the non survivor
      group this decline was much higher from 27.9 to 1.4. CONCLUSION: Low plasma D
      dimer suggests the absence of brain injury, and good prognosis.

PMID- 25386496
TI  - Relationship between 25-Hydroxy Vitamin-D and Obesity in 2-7 years old Children
      Referred to a Paediatric Hospital in Iran.
AB  - BACKGROUND: Obesity is increasing in children and it can cause many complications
      in adulthood, such as Diabetes mellitus (DM) and metabolic syndrome. In
      observational studies, vitamin-D was one of the factors which were found to be
      associated with obesity. AIMS: To determine the association between body mass
      index (BMI) and serum level of vitamin-D in children who were outpatients at
      Taleghani Paediatric Hospital, Iran. SETTINGS AND DESIGN: This was a cross
      sectional observational study done on 215 children who were 2 to 7 y old, who
      were referred to Taleghani Hospital in winter (1391 solar calendar) 2013.
      MATERIALS AND METHODS: In this cross-sectional study, anthropometric indices:
      weight, height and waist circumference were measured by using identical
      instruments. BMI was also determined as per CDC 2000 criteria. Vitamin-D levels
      were estimated by ELISA. STATISTICAL ANALYSIS: Vitamin-D levels which were less
      than 20 nmol/L were considered as a deficiency, levels which were 20-30 nmol?L
      were considered as inadequate and those which were equal to or greater than 30
      nmol?L were considered as sufficient. t-test, ANOVA and Pearson's correlation
      coefficient at a significant level of 0.05 were applied and data were analysed by
      using SPSS (version 16). RESULTS: One hundred and twenty five children (47.4%)
      were males and the rest were females. One hundred eighty four children (85.6%)
      had vitamin-D deficiency and only 31 had adequate levels of vitamin-D. The
      prevalence of obesity and overweight were 27%, but considering the vitamin-D
      status, it was found to be insignificant. However, there was a linear
      relationship between waist circumference and serum vitamin-D (p<0.01). The means
      and standard deviations of serum vitamin-D levels in girls and boys were 22.76 +/
      11.62 and 23.46 +/- 9.30 nmol/L and this difference was not significant. Vitamin
      D levels found in the three ethnic groups of Fars, Turkmen and Sistani showed
      significant differences (p<0.002). CONCLUSIONS: There was a high prevalence of
      vitamin-D deficiency in 2 to 7 year olds. There was no significant relationship
      between BMI and vitamin-D, but it was recorded in ethnic groups, and there was a
      correlation between waist circumference and vitamin-D levels. More exposure to
      sunlight and prescription of vitamin supplements were recommended.

PMID- 25386497
TI  - Button battery ingestion-case report and review.
AB  - Over the last few years there is a rise in use of button batteries in various
      toys and other electronic gadgets. Easy availability and small size of these
      batteries pose a significant risk of ingestion in small children. Button battery
      ingestion can lead to serious health hazards very rapidly. A case of button
      battery ingestion is presented in this paper. 

PMID- 25386498
TI  - Diagnostic Utility of PET CT in Thymic Tumours with Emphasis on 68Ga-DOTATATE PET
      CT in Thymic Neuroendocrine Tumour - Experience at a Tertiary Level Hospital in
      India.
AB  - INTRODUCTION: 18 Fluorine-fluoro-2-deoxyglucose positron emis-sion
      tomography/computed tomography (18F- FDG-PET/CT) is of importance in assessing
      high-risk thymoma and thymic carcinomas. Detection of advanced thymoma versus
      thymic carcinoma by routine cross sectional anatomical imaging such as computed
      tomography (CT), magnetic resonance imaging (MRI) often poses a diagnostic
      dilemma. In this case series we observed the utility of FDG uptake to predict
      advanced thymoma and distinguish thymoma from thymic cancer. MATERIALS AND
      METHODS: We reviewed 18F- FDG-PET/CT scans of 12 patients (8 males, 4 females);
      age 24-60yrs with thymic epithelial malignancy from January 2011 to May 2013. FDG
      activity in lesions was quantified using maximum standardised uptake value
      (SUVmax) and correlated with Masaoka staging and WHO classification. All patients
      fasted 4 hr prior to 18F-FDG PET/CT. Images from vertex to mid-thigh were
      acquired 60min post injection of 3.7 -4.7 MBq/kg (Mega Becquerel)/kilogram of18F
      FDG and SUV max of each tumour was measured. One patient underwent DOTATATE scan,
      received 138MBq of 68Gallium (68Ga)-DOTATATE injection IV and imaging was done
      after 60 min. RESULTS: Higher FDG uptake of SUVmax 7.35 was seen in type B3
      thymoma. FDG uptake was higher in thymic carcinoma (20.45 in primary and 17.46 in
      the node) or neuroendocrine differentiation (NED) than in patients with thymomas
      (ranged 7.35 - 3.02). No significant association was observed between higher
      focal FDG uptake and advanced-stage disease in thymoma. In NED 68Ga - DOTATATE
      imaging identified more lesions than in FDG. CONCLUSION: PET CT is a valuable
      diagnostic tool in evaluation of thymic tumours, to assess in initial workup, for
      treatment response and for prognostication. 68Ga-DOTATATE PET/CT is beneficial in
      assessing neuroendocrine thymic tumours. Focal FDG uptake cannot predict advanced
      thymoma but is helpful in distinguishing thymoma from thymic carcinoma, or the
      more aggressive thymoma B3.

PMID- 25386499
TI  - Synchronous presentation of chronic myeloid leukemia with carcinoma penis: a rare
      presentation.
AB  - We report here a case of 52-year-old male presenting with penile ulcer. On
      evaluation, he was diagnosed to have Carcinoma penis with concurrent CML in
      chronic phase. Clinical examination showed pallor, bilateral inguinal
      lymphadenopathy, bilateral pitting pedal oedema and hepatosplenomegaly. He was
      diagnosed to have chronic myeloid leukemia based on peripheral smear examination
      showing raised counts with shift to left and fluorescence in situ hydridisation
      (FISH) showing t (9:22). The ilio-inguinal block dissection specimen showed
      inguinal metastasis of squamous cell carcinoma (SCC). This case is being
      presented here in view of the rarity in combination of CML with another
      malignancy. 

PMID- 25386500
TI  - Prevelance of Haller's Cells: A Panoramic Radiographic Study.
AB  - BACKGROUND: Infraorbital ethmoid cells, also known as Haller's cells can be seen
      on panoramic radiographs. These help in identification of various pathologies and
      patient symptoms. OBJECTIVE: To determine the prevelance and characteristic of
      Haller's cells on panoramic radiographs. Infraorbital ethmoid cells are
      extensions of ethmoid air cells into areas of orbit and maxillary sinus.
      MATERIALS AND METHODS: This study comprised of 1000 panoramic radiographs of
      healthy adults of the age 18-80 years. Each radiograph was interpreted for the
      presence of haller's cells. The data collected were then tabulated and subjected
      to descriptive statistics and chi-square test. RESULTS: Haller's cells were
      observed in 19.2% patients. Majority of cells were present unilaterally (176
      cells) while only 15 were seen bilaterally. Maximum cells were oval in shape,
      unilocular and single in number. CONCLUSION: Presence of haller's cells helps in
      enumerating the differential diagnosis for orofacial pain and in avoiding
      surgical complications in endonasal procedures.

PMID- 25386501
TI  - Diagnostic accuracy of high resolution ultrasound to differentiate neoplastic and
      non neoplastic causes of cervical lymphadenopathy.
AB  - INTRODUCTION: Lymph nodes are normal structures distributed throughout the human
      body and are enlarged in various disease entities. Identifying the relevant lymph
      nodes is important in treating these patients. High resolution sonography (HRSG)
      and fine needle aspiration cytology (FNAC) play crucial role in planning the
      treatment. OBJECTIVE: To assess the diagnostic accuracy of HRSG differentiate
      neoplastic and non neoplastic causes of enlarged cervical lymph nodes. MATERIALS
      AND METHODS: HRSG evaluation of enlarged cervical lymph nodes were performed to
      differentiate neoplastic from non neoplastic lymph nodes followed by FNAC
      correlation and the accuracy of HRSG was studied. RESULTS: One hundred and
      fourteen lymph nodes of 106 patients were analysed to accomplish the study
      objective. In our study, HRSG had 96% sensitivity and 90.6% specificity for
      differentiating between neoplatic and non-neoplastic cervical lymphadenopathy.
      Similarly positive and negative predictive values were 88.9% and 96.7%
      respectively. Overall accuracy of HRSG was 93%. CONCLUSION: Owing to high
      sensitivity and negative predictive value, HRSG with Doppler is an excellent
      first line investigating tool for enlarged lymph nodes and avoids invasive
      procedures like FNAC in cases of reactive/ inflammatory (non-neoplastic) lymph
      nodes. However, neoplastic diagnosis of HRSG needs further confirmation by FNAC.

PMID- 25386502
TI  - Sylvian Fissure Dermoid Cyst - A Rare case.
AB  - Intracranial dermoid cysts are rare tumours which usually occur in the midline.
      Sylvian fissure is a very unusual site for this lesion. This case presents a
      patient with unruptured dermoid cyst in the left sylvian fissure who was operated
      successfully without any residual deficit. 

PMID- 25386503
TI  - Acute mesenteric ischemia with intrasplenic gas: a rare occurence.

PMID- 25386504
TI  - Pneumocystis Pneumonia - A Novel Complication in a Non-HIV Dengue Patient.

PMID- 25386505
TI  - Extra Large Temporal Tunnel Cataract Extraction [ETCE].
AB  - PURPOSE: To determine the outcomes of extra large temporal sclero-corneal tunnel
      incision Cataract Surgery. MATERIALS AND METHODS: This consecutive case series of
      eyes undergoing temporal tunnel cataract extraction with tunnel length of 8 to 10
      mm was identified retrospectively. Surgical procedure details, follow up,
      complications, visual and astigmatic outcomes at 6wks were recorded and analysed.
      RESULTS: Ninety six eyes with extra large tunnel incision were identified for
      analysis from a dataset of 670 manual small incision cataract surgery cases. 58%
      eyes had NO5 or denser cataracts. Intraoperative complications included, tunnel
      related problems (1 eye, 1.04%), bleeding into Anterior Chamber (10 eyes, 10.4%),
      Posterior Capsular Rent (2 eyes, 2.1%). Early postoperative complications
      included striate keratopathy (7 eyes, 7.3%). The mean Best Corrected Visual
      Acuity was 6/7.5 (0.1 logMAR) and 98% cases had Best Corrected Visual Acuity of
      6/12 (0.3 logMAR) or better at 6wk. The aggregate Surgically Induced Astigmatism
      was 0.32D at 85(0). CONCLUSION: Extra Large Tunnel of length 8 to 10 mm can be
      self sealing with low SIA. The complication rates and visual outcomes of ETCE are
      comparable to those of conventional MSICS. This method can be valuable in
      complicated cases and during learning period.

PMID- 25386506
TI  - Occupational Mental Health: A Study of Work-Related Mental Health among Clinical
      Nurses.
AB  - OBJECTIVE: This paper reports a study performed to investigate and assess the
      mental health as well as the demographic characteristics of nurses to examine
      their mental health status based on four physical, anxiety, social-function and
      depression items. MATERIALS AND METHODS: This descriptive cross-sectional study
      was accomplished on 86 nurses working at three hospitals, affiliated to Iranian
      health ministry, in Ilam city(western Iran) all the cases were selected by
      purposeful sampling method. Data was collected by a two-part questionnaire
      containing individual data and GHQ -28 Standardized Questionnaire. The GHO-28 was
      developed by Goldberg, in 1978, as a screening tool to detect those likely to
      have or be at risk of developing psychiatric disorders. The GHQ-28 is a 28-item
      measure of emotional distress in medical settings. Analysis was done by SPSS 18
      software. RESULTS: The majority of participants were females(50.6 vs.49.4) of 35
      40 years old(27.2% ), 84 percent were married(vs.16%), 35.8 percent with 10-15
      years of record(vs.33.3% less than 5), 22.2% with 5-10, and 8.6% with more than
      15-years of work record. The majority of participants have worked in surgical
      wards of hospitals. The analysis of GHQ results showed that 43.2%(n=35) of
      participants were suspected to suffer from mental disorders(vs.56.8% n=46 healthy
      participants); of all the suspected cases, 12.3% were supposed to have physical
      symptoms, 16% anxiety symptoms, 42% social dysfunction, and 6.2% symptoms of
      depression. In general, the participants demonstrated a Mean+/-SD of mental
      health score equal to 23.65+/-9.43. CONCLUSION: Research results showed that the
      high prevalence of depression, anxiety and stress symptoms among nurses is
      alarming. It was concluded that providing efficient adequate and appropriate
      support services for this group can result in more healthy nurses as well as
      promotion of public health.

PMID- 25386507
TI  - Relationship between loneliness, psychiatric disorders and physical health ? A
      review on the psychological aspects of loneliness.
AB  - Human beings are social species which require safe and secure social surroundings
      to survive. Satisfying social relationships are essential for mental and physical
      well beings. Impaired social relationship can lead to loneliness. Since the time
      of dawn, loneliness is perceived as a global human phenomenon. Loneliness can
      lead to various psychiatric disorders like depression, alcohol abuse, child
      abuse, sleep problems, personality disorders and Alzheimer's disease. It also
      leads to various physical disorders like diabetes, autoimmune disorders like
      rheumatoid arthritis, lupus and cardiovascular diseases like coronary heart
      disease, hypertension (HTN), obesity, physiological aging, cancer, poor hearing
      and poor health. Left untended, loneliness can have serious consequences for
      mental and physical health of people. Therefore it is important to intervene at
      the right time to prevent loneliness, so that physical and mental health of
      patients is maintained. 

PMID- 25386508
TI  - How to Write Articles that Get Published.
AB  - Publications are essential for sharing knowledge, and career advancement. Writing
      a research paper is a challenge. Most graduate programmes in medicine do not
      offer hands-on training in writing and publishing in scientific journals.
      Beginners find the art and science of scientific writing a daunting task. 'How to
      write a scientific paper?, Is there a sure way to successful publication ?' are
      the frequently asked questions. This paper aims to answer these questions and
      guide a beginner through the process of planning, writing, and correction of
      manuscripts that attract the readers and satisfies the peer reviewers. A well
      structured paper in lucid and correct language that is easy to read and edit, and
      strictly follows the instruction to the authors from the editors finds favour
      from the readers and avoids outright rejection. Making right choice of journal is
      a decision critical to acceptance. Perseverance through the peer review process
      is the road to successful publication. 

PMID- 25386509
TI  - Question vetting: the process to ensure quality in assessment of medical
      students.
AB  - Over the past decade, medical schools have made new efforts to provide accurate,
      reliable, and timely assessments of the competence of trainees. All methods of
      assessment have strengths and intrinsic flaws. Written examination questions
      forms an important item in knowledge assessment and are typically classified
      according to whether they are open-ended or multiple choices. At present
      questions are prepared casually just before the examination and are not put
      through any quality check to correct any possible mistakes or ambiguity in the
      questions. This may lead to confusion or wrong understanding of the questions by
      the students which will be reflected in their answers as well. Question Vetting
      is the process when an expert person examines or evaluates and edits questions to
      make it free of any mistakes. The importance of vetting and re-vetting of
      examination questions cannot be overstated in the present scenario of medical
      education. There is a prescribed structure and protocol of question setting and
      vetting for examinations in medical education programmes. The areas that need to
      be examined during question vetting are for technical accuracy, content level and
      language aspects. The use of the prescribed structure and protocol of question
      vetting ensures a consistently high standard of question presentation during
      examinations which will help the students to understand the questions better and
      to answer them correctly. This article is intended to highlight the importance of
      introducing question vetting in our medical education scenario in order to
      improve the quality of assessment of medical students. 

PMID- 25386510
TI  - Mixed dentition space analysis in kodava population: a comparison of two methods.
AB  - AIMS: To evaluate the reliability of Tanaka and Johnston and Moyer's (75th
      percentile) mixed dentition prediction methods in Kodava population sample, to
      formulate regression equations for predicting the mesiodistal widths of unerupted
      canines and premolars and to construct probability tables for the Kodava
      population. SETTINGS AND DESIGN: Data was obtained from Kodava subjects visiting
      the clinics for routine dental check up. MATERIALS AND METHODS: Dental models of
      30 male and 30 female Kodava subjects (age range is 16 - 23 yr) were used. Teeth
      measured included mandibular permanent incisors, maxillary and mandibular
      permanent canines, first and second premolars. Digital caliper calibrated to
      0.01mm was used to record mesiodistal dimensions. The actual teeth measurements
      were then statistically compared with the predicted values derived from the
      Tanaka and Johnston's equations and Moyers probability tables at the 75(th)
      percentile. STATISTICAL ANALYSIS USED: Descriptive statistics including means,
      standard deviations were calculated for the actual and predicted tooth sizes.
      Student's t-tests were performed to compare the differences between the measured
      mesiodistal widths of canine, first and second premolars and the predicted values
      derived from Moyers. Correlation and regression analysis were performed to
      formulate standard regression equations. RESULTS: Tanaka and Johnston prediction
      equations overestimated the mesiodistal widths of permanent canines and premolars
      in both the arches. Moyers 75(th) percentile also overestimated the actual
      measurements except for the maxillary arch in female subjects. The percentage of
      overestimation was more for Tanaka - Johnston prediction method than that of
      Moyers (75(th) percentile). Correlation and regression analysis were performed
      between the predicted and actual tooth size and standard regression equations
      were developed for the Kodava population. Probability tables were also
      constructed from the data obtained. CONCLUSION: The data from present study
      illustrates the limitation of Tanaka and Johnston regression equations and
      Moyer's (75(th) percentile) chart when applied to Kodava population. From this
      data, regression equations and probability tables were derived for tooth size
      prediction for Kodava population. This would be more accurate when applied to
      local children of Kodava community.

PMID- 25386511
TI  - Evaluation of soft and hard tissue changes after anterior segmental osteotomy.
AB  - OBJECTIVE: To determine the relationship between the changes of soft and hard
      tissues after anterior segmental osteotomy and to evaluate these changes using
      cepahalometric and photometric analyses. MATERIALS AND METHODS: Ten patients aged
      18-30 years who underwent anterior segmental osteotomy were included in the
      study. Preoperative and postoperative records consisted of lateral cephalogram
      and frontal and lateral photographs. Postoperative measurements were taken six
      months after surgery. RESULTS: Statistical analysis showed changes in both soft
      and hard tissue parameters. Changes were not uniform for all the parameters.
      Upper lip and upper incisor protrusion showed very large effect size whereas
      nasal tip inclination showed small effect and mentolabial angle showed no effect.
      CONCLUSION: Skeletal protrusion pose problem to orthodontists as they can't be
      corrected by orthodontics alone. Anterior segmental osteotomy in association with
      orthodontia is the choice of treatment. Anterior segmental osteotomy allows for
      functional and aesthetical correction with good success rate and minimal
      complication.

PMID- 25386512
TI  - An Insight Into Research Ethics among Dental Professionals in A Dental Institute,
      India- A Pilot Study.
AB  - BACKGROUND: Research activities are increasing in all the fields of medicine
      including dentistry but there is dearth of information about the knowledge,
      attitude and behaviour of dental professionals for ethical principles in
      research, especially in the developing countries like India. OBJECTIVE: To assess
      knowledge, attitude and behaviour among dental professionals pertaining to
      research ethics. MATERIALS AND METHODS: A self-administered, close ended
      questionnaire survey with cross-sectional design was conducted in a private
      dental institute in India. All the house-surgeons, post-graduate students and the
      faculty of the same institute were included for the assessment of the knowledge,
      attitude and behaviour regarding research ethics using a 24, 8 and 8 items.
      RESULTS: A total of 213 of 230 dental professionals participated (response rate
      of 92.6%). Mean knowledge, attitude and behaviour scores were 43.3%, 82.5% and
      46.37%, respectively. Significant correlations were observed of age and gender
      with the attitude about the research ethics among study subjects (chi(2)=14.383,
      p=0.006 and chi(2)=7.769, p=0.021, respectively). CONCLUSION: Participants had
      favorable attitude towards research ethics, but their knowledge and behaviour
      needs considerable improvements. The age and gender were associated with
      attitude. The present pilot study highlights the need for further nationwide
      study and development of research ethics curriculum in detail for dental
      education in India.

PMID- 25386513
TI  - Tobacco Cessation Counselling Practices and Attitude among the Dentist and the
      Dental Auxiliaries of Urban and Rural Areas of Modinagar, India.
AB  - BACKGROUND: The increasing use of tobacco among youths warrants the need for
      dental health professionals to effectively provide tobacco cessation counselling
      (TCC) in the office and community settings. However, there have been concerns
      among the dental professionals regarding TCC in dental settings. AIMS AND
      OBJECTIVES: To assess the attitude of dental professionals including the dentist
      and dental hygienist towards the TCC and identify the possible barriers towards
      the implementation of these practices in the rural and urban areas of Modinagar
      district. MATERIALS AND METHODS: The present questionnaire based survey was
      carried among the qualified dentist and dental hygienist from the urban and rural
      areas of the Modinagar district to attitudes in tobacco cessation, practices in
      tobacco cessation interventions and related barriers towards implementation. The
      survey data were analyzed using the SPSS 16 version software package. The
      descriptive statistics (frequency) was generated for the each question to assess
      their attitude and practice. RESULTS: The response rate of the questionnaire
      among the dentist and dental hygienist was 100%. The attitude of the majority of
      dentist towards the tobacco cessation counselling was positive as compared to the
      dental hygienist. 69.2% of the dentist were of the view that the dental health
      professionals should provide TCC as compared to 54.2% among the hygienist.
      Regarding the practice, only 12.5% and 5.8% of the dentist and dental hygienist
      had ever used the nicotine replacement therapy in their dental practice. The lack
      of the knowledge and information regarding TCC was the only perceived barrier
      among the dentists (51.7%) and dental hygienist (68.3%). CONCLUSION: Dental
      professionals must expand their horizon and armamentarium to include TCC
      strategies inclusive of their regular preventive and therapeutic treatment
      modalities. Also, the dental institutions should include TCC into the curriculum,
      but it should not be just theoretical knowledge rather it must have a practical
      component.

PMID- 25386514
TI  - Estimation of salivary and serum total sialic Acid levels in periodontal health
      and disease.
AB  - BACKGROUND: Chronic gingivitis and periodontitis are inflammatory diseases. An
      important function of host sialic acid is to regulate innate immunity. The aim of
      the study was to assess the concentration of Total sialic acid (TSA) in saliva
      and serum and also to find out their association if any, in periodontal health
      and disease. MATERIALS AND METHODS: A total of 90 subjects were clinically
      examined and distributed into three groups (n=30) according to the periodontal
      status namely healthy, chronic gingivitis and chronic periodontitis.Clinical
      measurements including probing depth, clinical attachment level, gingival index,
      oral hygeine index were recorded .TSA concentration was determined in saliva and
      serum of all subjects. RESULTS: In healthy group the mean salivary TSA level was
      39.05mg/dl +/-6.35(p<0.0001), mean serum TSA level was 49.75 mg/dl +/- 4.87
      (p<0.0001). In the chronic gingivitis group the mean salivary TSA level was 68.23
      mg/dl +/- 2.71 (p<0.0001), mean serum TSA level was 65.65 mg/dl +/-3.56
      (p<0.0001). In the chronic periodontitis group the mean salivary TSA was 81.33
      mg/dl +/-3.94 (p<0.0001), mean serum TSA level was 75.98 mg/dl +/-3.58
      (p<0.0001). CONCLUSION: The present data indicates that salivary & serum TSA
      levels can differentiate between chronic periodontitis patients and normal
      individuals. Thus it can be used as an adjunct to diagnose, monitor response to
      therapy, to determine the current periodontal disease status and to assess the
      treatment outcomes.

PMID- 25386515
TI  - Evaluation of the Luting Cement Space for Provisional Restoration by using
      Various Coats of Die Spacer Materials-An Invitro Study.
AB  - AIM: The present study was to evaluate the space provided for the temporary
      luting cement, after the application of various coats of die spacers, during the
      fabrication of provisional crowns and bridges. MATERIALS AND METHODS: A total of
      50 specimens of dental stone with provisional crowns on all these samples were
      prepared and were divided into five groups based on the application of various
      coats of different die spacers. Later these specimens were sectioned
      buccolingually and were observed using a stereomicroscope under 100X
      magnification. The images thus obtained were evaluated and noted for the amount
      of space between the inner surface of the provisional crown and the specimens at
      five different locations using Image Pro 6.0 Express software and the values were
      subjected to one-way ANOVA test, and unpaired t-test. RESULTS: There was a
      significant increase of luting space thickness with various die spacer
      applications than the specimens of control group. CONCLUSION: Specimens of double
      coat applications of silver and gold die spacers showed higher luting cement
      space than the separating media application specimens.

PMID- 25386516
TI  - En-masse Retraction of the Maxillary Anterior Teeth by Applying Force from Four
      Different Levels - A Finite Element Study.
AB  - OBJECTIVE: To find out if it is possible to control maxillary anterior teeth in
      sagittal and vertical plane during retraction by altering the vertical levels of
      force application in the posterior region, i.e. identifying the type of movement
      of the maxillary anterior teeth which occurs when force would be applied from
      four different levels i.e. High, Medium, and Low pull Implants and from a
      conventional Molar hook and also to quantify the retraction and intrusion
      components of force thus setting a guideline for the implant height placement.
      MATERIALS AND METHODS: A Finite Element Model of maxillary dentition along with
      alveolar bone, brackets and wire was developed with defined material properties.
      The model was analysed to calculate the displacement when force was applied from
      different levels. RESULTS: From all points of force application, anterior teeth
      tipped lingually in the sagittal plane, whereas in the vertical plane extrusion
      was seen when retracted from molar hook and intrusion was seen when retracted
      from implants. For every mm of apical displacement of implant, the retraction
      component of force reduces approximately by around 1% and intrusion component of
      force increases approximately by around 0.3%. CONCLUSION: Based on the results of
      this study we can reckon that by changing the position of implant in vertical
      plane one will have very little effect on the type of tooth movement. As the
      point of force application moves apically, type of tooth movement in the sagittal
      plane remained almost constant and in vertical plane intrusion is slightly
      increased.

PMID- 25386517
TI  - Perception towards serving rural population amongst interns from dental colleges
      of haryana.
AB  - BACKGROUND: The problem of reluctance of dentists to work in rural areas is an
      international phenomenon. With an increase in number of dental colleges in India,
      there also has been an improvement in the dentist to population ratio. But still
      there exists a wide disparity in dentist to population ratio in rural and urban
      areas. The aim of this study was to find the perception of dental interns towards
      serving rural population and the reasons associated with their choices. MATERIALS
      AND METHODS: To know the willingness of dental interns to serve rural population
      and factors associated with their decision, 504 participants from six dental
      colleges of Haryana were interviewed. A pre-tested self-administered structured
      questionnaire was used for data collection. Descriptive statistics were used for
      data summarization and presentation. Degree of association was measured by Chi
      Square test, with significance level set at p < 0.05. RESULTS: Out of total
      participants, 55.95% were willing to serve in rural area. Less competition in
      settling (46.45 %) was the prime factor for willingness, priority for
      postgraduation (45.01%) was main factor for reluctance. No significant difference
      (p=0.365) was seen in the perception of young dentists towards serving rural or
      urban population. CONCLUSION: Even though the current statistics don't reflect a
      satisfactory dentist to population ratio in rural areas, the attitudes of the
      dental students towards practicing in rural areas were found to be good.

PMID- 25386518
TI  - Oral Hygiene Practices and Dentition Status of Public Transport Workers of India-
      A Cross-sectional Study.
AB  - OBJECTIVES: To evaluate the oral hygiene practices and dentition statuses of
      transport workers who were working in a public bus transport system (C.T.U.) of
      Chandigarh (U.T.), India. MATERIALS AND METHODS: The data were recorded on a
      modified W.H.O. format (1997). A total of 1008 subjects constituted the final
      sample size. Information was obtained regarding the oral hygiene practices and
      clinical examinations were conducted. Statistical analysis was done by using
      ANOVA and Z-test. RESULTS: The mean age of the subjects was 45.3 +/- 7.8 years.
      Mean DMFT of the subjects who were not using tobacco in any form was 5.02. 80.2%
      (808). 88.7% of the subjects brushed their teeth as least once a day. Mean number
      of decayed and missing teeth were 1.67 +/- 2.16 and 1.46 +/- 2.8, respectively
      and their relation with age was found to be statistically significant.
      CONCLUSION: Dental caries was found to be major indication in all the age groups.
      More elderly subjects than young needed extractions. This study emphasized the
      need of an improved dental awareness and availability of dental facilities to
      transport workers.

PMID- 25386519
TI  - Comparative evaluation of maximum bite force in dentulous and edentulous
      individuals with different facial forms.
AB  - PURPOSE: The purpose of this study was to evaluate the mean maximum bite force in
      dentulous and edentulous individuals with Angle's class-I occlusion and to assess
      the effect of different facial forms such as Square, Square-tapering, tapering
      and ovoid on the biting force. MATERIALS AND METHODS: The study consisted of 160
      subjects in total. Out of these 160, 80 were dentulous subjects and remaining 80
      were edentulous subjects who had received treatment for his/her missing teeth by
      fabrication of a complete denture. The mean maximum voluntary bite force for
      every subject was measured using bite force measuring device,(Process indicator
      3016). Face form was divided under square, tapering, square-tapering or oval
      types. The shape of the face was determined using digital photographs. The effect
      of edentulism, gender and face form on bite force was statistically analyzed
      using ANOVA, Scheffe and Sample t-tests. RESULT: Mean maximum bite force and
      standard deviation (S.D.) in the dentulous sample population was 41.3(13.9)
      kilograms (kg) which when compared with the edentulous sample population provided
      highly significant statistical result. The mean maximum biting force in
      edentulous sample population was 4.43 (2.4) kg (p<0.001). In both dentulous and
      edentulous categories, the mean maximum bite force was statistically higher in
      male patients than female patients. Mean maximum bite force was significantly
      higher in patients with square facial form than in subjects with other facial
      forms. CONCLUSION: Square face form contributes to higher bite force values by
      obtaining higher Mechanical advantage from muscles of mastication. RESULT also
      proved that patients with complete denture with any facial form have much lower
      mean maximum bite force when compared to dentate subjects.

PMID- 25386520
TI  - Health from the hive: propolis as an adjuvant in the treatment of chronic
      periodontitis - a clinicomicrobiologic study.
AB  - OBJECTIVES: This study was aimed at the clinical and microbiological evaluation
      of the efficacy of subgingivally delivered Indian propolis extract as an adjunct
      to scaling and root planing (SRP) in the treatment of periodontitis. MATERIALS
      AND METHODS: Twenty patients diagnosed with chronic periodontitis presenting a
      minimum of two pockets (probing depth >=5 mm) were selected. Sites were assigned
      randomly into control sites (n=20) which received SRP alone or test sites (n=20)
      which received SRP and locally delivered propolis. At selected sites, the
      clinical parameters were assessed and subgingival plaque samples were collected
      at baseline, 15 days and one month. The samples were cultured anerobically for
      periodontal pathogens. RESULTS: The results indicated that there was a
      significant improvement in both clinical and microbiological parameters (p<0.01)
      in the test sites compared to the control sites at the end of the study.
      CONCLUSION: Subgingival delivery of propolis showed promising results as an
      adjunct to SRP in patients with chronic periodontitis when assessed by clinical
      and microbiological parameters.

PMID- 25386521
TI  - Evaluation of masseter muscle hypertrophy in oral submucous fibrosis patients -an
      ultrasonographic study.
AB  - BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic insidious disease of the
      oral mucosa, commonly seen in South East Asia. It occurs mainly due to the habit
      of quid or gutkha chewing. There is a clear dose dependent relationship between
      gutkha chewing and development of OSMF, also due to continuous chewing for larger
      intervals of time unnecessary forces are exerted on the muscles mainly the
      masseter muscle. So, the present study was done to evaluate the thickness of
      masseter muscle in OSMF patients and to compare it with normal patients.
      MATERIALS AND METHODS: The present study involved 50 subjects, 25 OSMF patients
      and 25 normal individuals. The thickness of masseter muscle was evaluated by
      ultrasonography (5-11mHz). RESULTS: There is a positive association between
      masseter muscle hypertrophy and OSMF (p-value 0.001). Thickness of masseter
      muscle was found to be more in OSMF patients as compared to control group and
      also thickness is more during contraction as compared to relaxation in both OSMF
      patients and normal individuals.

PMID- 25386522
TI  - Prevalence of dentin hypersensitivity and related factors among adult patients
      visiting a dental school in andhra pradesh, southern India.
AB  - BACKGROUND AND AIM: Dentine hypersensitivity (DH) is a relatively common problem
      which may disturb the patient during eating, drinking, brushing and sometimes
      even breathing. It is a painful condition highly prevalent in the general adult
      population. The aim of this study is to determine the prevalence of DH and to
      examine some associated factors such as initiating stimuli among adult patients.
      MATERIALS AND METHODS: The study is done under two phases. In the first phase a
      cross-sectional study was carried out in 665 study volunteers. Only 212 adult
      patients who were meeting the inclusion and exclusion criteria were conveniently
      selected to the study. A detailed demographic data and a structured questionnaire
      regarding type of response, sensitivity episodes, and duration of sensation, and
      stimulus for initiation were recorded by the examiner. Evidence of DH was
      confirmed by the use of air blast and water from the air-water jet of the dental
      chair and scratching the suspected tooth surfaces which is indicated by study
      subjects with a dental probe and noting the responses by using visual analog
      scale (VAS). In the second phase the related factors or characteristics of DH
      were surveyed. Statistical analysis preformed by using methods of descriptive
      statistics and Kruskal Wallis test. RESULTS: The overall prevalence of DH was
      found to be 32%. The most common cause was consuming cold food or drinks (92%)
      and common predisposing factor was gingival recession (28%). Probe method yields
      a higher VAS score followed by Air at 10 seconds and Water at 10 seconds which is
      statistically significant. CONCLUSION: The prevalence of DH in present study was
      32% which is attributed to gingival recession as predisposing factor and cold
      stimuli.

PMID- 25386523
TI  - Histological and Histometrical Evaluation of two Synthetic Hydroxyapatite Based
      Biomaterials in the Experimental Periodontal Defects in Dogs.
AB  - AIM: The present study was to evaluate histologically and histometrically the
      efficacy of Chitra granules in the regeneration of alveolar bone and to compare
      it with that of OsteoGenR (HA Resorb)(TM) in iatrogenically created alveolar bone
      defects in mongrel dogs. MATERIALS AND METHODS: Four dogs (16 sites) were used
      for this split-mouth study. The animals were divided randomly into two groups of
      two animals. Same animals were used as control and test. Each dog had four
      implantation sites. The periodontal defects were prepared by acute defect model.
      Animals were sacrificed at 3 months (n=2), 6 months (n=2) and histologic and
      histometric evaluation was carried out. STATISTICAL ANALYSIS: The data was
      analysed using statistical package Graph pad Software. Comparison of the hard and
      soft tissue parameters in the two groups was done using the Wilcoxan (Man
      Whitney), two tailed t-test. A p-value less than 0.05 were considered
      significant. RESULTS: Maturing bone with immature periodontal ligament fibers
      were observed at three months and advanced osteogenesis at six months with both
      the types of bone graft materials. The mean values showed that amount of new bone
      formed with OsteoGenR (HA Resorb)(TM) was slightly more than that obtained by
      Chitra granules in histometric evaluation. CONCLUSION: Histological study showed
      similar healing pattern with both the types of bone graft materials with maturing
      bone at 3 months and advanced osteogenesis at six months in experimental
      intraosseous periodontal defects in dogs. However, histological evaluation for
      longer period is necessary to determine the time taken for complete replacement
      of the bone graft materials with new bone.

PMID- 25386524
TI  - Dentition Status, Treatment Needs and Risk Predictors for Dental Caries among
      Institutionalised Disabled Individuals in Central India.
AB  - INTRODUCTION: Children and adolescents with disabilities appear to have poorer
      oral health than their non-disabled counterparts. Individuals with disabilities
      or illnesses receive less oral care than the normal population. OBJECTIVE: To
      determine the dentition status, treatment needs and risk predictors for dental
      caries of the institutionalized disabled individuals. MATERIALS AND METHODS: A
      descriptive cross-sectional study was conducted with pre-tested questionnaire
      among 330 institutionalised disabled individuals in the age range from 3 to 22
      years. The Dentition status and treatment needs were assessed by using WHO Oral
      health Proforma 1997. ANOVA test, chi-square test and backward conditional
      logistic regression analysis were performed. RESULTS: The mean DMFT for all the
      groups was 1.26 and the mean deft was 0.59. Backward conditional logistic
      regression revealed that only age categories and disability types were
      significantly associated with dental caries. Individuals who were mentally
      retarded (OR=1.36) and in the age group of 13-17 y (OR=1.91) were more likely to
      develop dental caries. CONCLUSION: The findings of the present study showed that
      overall caries experience was low but the treatment need was high among these
      institutionalized disabled individuals.

PMID- 25386525
TI  - Dental and skeletal maturity- a biological indicator of chronologic age.
AB  - INTRODUCTION: Precise evaluation of the developmental stage of a child is not
      only an integral part of both diagnosis and treatment of paediatric patients; it
      is also essential in Forensic Medicine and Dentistry. Physiologic age can be
      estimated by somatic, sexual, skeletal and dental maturity. AIM: Investigate the
      relationship between the dental age (DA) and skeletal age (SA) of children and
      comparing it with the chronological age (CA). MATERIALS AND METHODS: The dental
      age estimation methods of Schour and Massler (S&M), and Demirjian and Goldstien
      (D&G) and skeletal assessment methods of Greulich and Pyle (G&P), and Tanner et
      al., (TW2) were used to analyze the orthopantomograms and hand-wrist radiographs
      respectively of 150 healthy subjects within the age range of 5-15 y and compared
      with the Chronological Age. STATISTICAL ANALYSIS: Data collected was
      statistically analysed using the SPSS version 15.0 STATISTICAL ANALYSIS Software.
      For all tests p-value of <0.05 were considered statistically significance.
      RESULTS: Dental age estimation techniques were found comparable and equally
      reliable as the skeletal age estimation methods. Strong correlations between
      dental and skeletal maturation were demonstrated.

PMID- 25386526
TI  - Effect of four surface treatment methods on the shear bond strength of resin
      cement to zirconia ceramics- a comparative in vitro study.
AB  - BACKGROUND: Improving the retention of zirconia-based ceramics is desirable in
      order to avoid the failure of crowns and fixed partial dentures .This can be
      achieved by creating micromechanical retention using surface treatments.
      Therefore, it becomes necessary to constantly compare and re-evaluate the
      influence of different surface treatment methods on the bond strength . AIM: To
      evaluate the effect of four different surface treatments on shear bond strength
      between zirconia surface and resin cements. SETTINGS AND DESIGN: Observational
      study. MATERIALS AND METHODS: Twenty five zirconia plate samples were prepared
      based on ISO standards and were divided into five groups and each group was
      subjected to following five different surface treatments : no treatment,
      sandblasting with 110 MUm alumina, sandblasting with 250 MUm alumina, acid
      etching with 9.6% hydrofluoric acid and laser radiation on the surface. All the
      samples were surface disinfected and were embedded in blocks of autopolymerising
      resin to check shear bond strength on the universal testing machine. Statistical
      analysis used-data was analyzed using one-way ANOVA and a Post Hoc Bonferroni
      test. RESULTS: Analysis of the data showed that the highest shear bond strength
      values were obtained with laser treatment (18.120 +/- 0.8159 Mpa). The lowest
      values were obtained with control group (9.166 +/- 0.569 Mpa). Laser treatment
      increased the shear bond strength values significantly (p<0.05). CONCLUSION:
      Surface treatments increased the bond strength between zirconia and resin cement
      and carbon dioxide laser could be an effective surface treatment for increasing
      bond strength.

PMID- 25386527
TI  - Qualitative histological evaluation of hard and soft tissue components of human
      permanent teeth using various decalcifying agents - a comparative study.
AB  - INTRODUCTION: Decalcification is the commonly employed technique in
      histopathology laboratories as a part of calcified tissue preparation for the
      microscopic examination. Chemical agents are most commonly used for routine
      decalcification procedures, though some agents adversely affect the tissue
      integrity and staining properties. AIM: To compare the efficacy of various
      decalcifying agents by histological evaluation of hard and soft tissue components
      of teeth. MATERIALS AND METHODS: The five decalcifying agents namely 10% Nitric
      acid (HNO3), 10% Formal nitric acid (FNA), 10 % Formic acid (FA), 8% Potassium
      formate (KF) + 8% Formic acid (FA) and Neutral Ethylenediamenetetracetic acid
      (EDTA) were used to decalcify 60 human permanent teeth. The specimens were
      subjected to routine processing, sectioning and staining with hematoxylin and
      eosin. The stained sections were observed under light microscope by three
      independent observers and grading was done. STATISTICAL ANALYSIS: Paired sample t
      test was done for inter-observer variation. One-way-ANOVA and Post-hoc test was
      applied to compare the effects of different decalcifying agents. RESULTS:
      Considering preservation and staining characteristics of both hard and soft
      tissues, superior results were obtained with 10% HNO3 followed by 10% FNA and
      EDTA which was according to the respective mean values obtained. But
      statistically significant difference was shown only with 10% FA & 8% KF + 8% FA.
      CONCLUSION: HNO3 was showing the most efficient result as it balances both tissue
      integrity and time factor suggesting that it can be used as a stable decalcifying
      agent for routine histopathological diagnosis.

PMID- 25386528
TI  - "Evaluation of the Effect of Ultraviolet Disinfection on Dimensional Stability of
      the Polyvinyl Silioxane Impressions." an in-Vitro Study.
AB  - INTRODUCTION: Infection control is an important concept in the present day
      practice of dentistry. The prosthodontists are at an added risk of transmission
      because of the infection spreading through the contaminated lab equipments while
      working in the lab. The purpose of this study is to evaluate the effect of UV
      light disinfection on dimensional stability of polyvinyl siloxane impressions.
      Materials and Methods : Impressions were made in perforated custom tray. After
      polymerization of impression, half the samples were disinfected in UV light and
      remaining samples were not subjected to disinfection and poured in die stone
      which served as control group. Linear dimensions were measured on the cast with
      travelling microscope of 0.001accuracy. Result : The result showed that UV light
      disinfectant showed no significant dimensional changes on impressions.
      CONCLUSION: Hence, it can be safely used to disinfect impressions in clinical
      prosthodontic procedures.

PMID- 25386529
TI  - Clinical evaluation of papilla reconstruction using subepithelial connective
      tissue graft.
AB  - OBJECTIVE: The aesthetics of the patient can be improved by surgical
      reconstruction of interdental papilla by using an advanced papillary flap
      interposed with subepithelial connective tissue graft. MATERIALS AND METHODS: A
      total of fifteen sites from ten patients having black triangles/papilla recession
      in the maxillary anterior region were selected and subjected to presurgical
      evaluation. The sites were treated with interposed subepithelial connective
      tissue graft placed under a coronally advance flap. The integrity of the papilla
      was maintained by moving the whole of gingivopapillary unit coronally. The
      various parameters were analysed at different intervals. RESULTS: There was a
      mean decrease in the papilla presence index score and distance from contact point
      to gingival margin, but it was statistically not significant. Also, there is
      increase in the width of the keratinized gingiva which was statistically highly
      significant. CONCLUSION: Advanced papillary flap with interposed sub-epithelial
      connective tissue graft can offer predictable results for the reconstruction of
      interdental papilla. If papilla loss occurs solely due to soft-tissue damage,
      reconstructive techniques can completely restore it; but if due to periodontal
      disease involving bone loss, reconstruction is generally incomplete and multiple
      surgical procedures may be required.

PMID- 25386530
TI  - Common Matrix Metalloproteinases (MMP-8, -9, -25, and -26) Cannot Explain
      Dentigerous Cyst Expansion.
AB  - OBJECTIVE: Mechanisms of the dentigerous cyst formation from the normal eruption
      follicle is unknown but disturbances in the proteolytic activity have been
      suspected, since the growth of these cysts is accompanied by local bone
      destruction. The aim of the present study was to evaluate the expression of
      matrix metalloproteinases (MMP) in human dental dentigerous cysts and healthy
      dental follicles. MATERIALS AND METHODS: We studied 10 patients with dentigerous
      cysts and 10 healthy dental follicles from the lower jaw in respect to their
      immunoexpression of MMPs -8, -9, -25, and -26 and tissue inhibitor of
      metalloproteinases -1 (TIMP-1). RESULTS: MMP-8 was expressed slightly more in
      cyst epithelium than in odontogenic epithelium of healthy controls dental
      follicle but the difference lacked statistical difference. Other MMPs and TIMP-1
      did not differ regarding the studied specimens. CONCLUSION: Differences in MMP
      expression cannot solely explain the cyst expansion suggesting the potential
      involvement of other osteolytic mechanisms.

PMID- 25386531
TI  - Photoelastic stress analysis in prosthetic implants of different diameters: mini,
      narrow, standard or wide.
AB  - PURPOSE: This study investigated the biomechanical behavior of screwed partial
      fixed prosthesis supported by implants with different diameters (2.5 mm; 3.3 mm
      and 3.75 mm) by using a photoelastic analysis. MATERIALS AND METHODS: Six
      photoelastic models were fabricated in PL-2 resin as single crowns or splinted 3
      unit piece. Models were positioned in a circular polariscope and 100-N axial and
      oblique (45 degrees) loads were applied in the occlusal surface of the crowns by
      using a universal testing machine (EMIC). The stresses were photographically
      recorded and qualitatively analyzed using a software (Adobe Photoshop). RESULTS:
      Under axial loading, the number of fringes was inversely proportional to the
      diameter of the implants in the single crown models. In the splinted 3-unit
      piece, the 3.75-mm implant promoted lower number of fringes regardless of loading
      area application. Under oblique loading, a slight increase of fringes number was
      observed for all groups. CONCLUSION: The standard implant diameter promoted
      better stress distribution than the narrow and mini diameter implants.
      Additionally, the splinted crowns showed a more uniform stress distribution.

PMID- 25386532
TI  - Expression of Endoglin (CD-105) and Microvessel Density in Oral Dysplasia and
      Squamous Cell Carcinoma.
AB  - OBJECTIVE: To assess the expression of Endoglin (CD-105) and Microvessel Density
      in clinically normal oral mucosa of non-tobacco and tobacco habituated patients &
      also histopathologically confirmed cases of oral squamous cell carcinoma (OSCC)
      patients. MATERIALS AND METHODS: Twenty cases of clinically normal oral mucosa
      with tobacco habituation in the form of chewing or smoking, 20
      histopathologically confirmed cases of OSCC and twelve normal healthy oral
      mucosal cases without tobacco habituation in any form, served as control group,
      were immunohistochemically analysed for expression of Endoglin (CD-105). Chi
      square test is used to determine statistical analysis and significance. RESULT &
      CONCLUSION: The finding of 65% of Endoglin CD - 105 positivity and microvessel
      density (MVD) in the mucosal specimens of tobacco users may be attributed as
      neoangiogenesis or angiogenic squamous dysplasia like phenomenon occurring as
      important pathological biomarker preceding oral cancer development, and may
      therefore be useful as a predictive marker of malignancy.

PMID- 25386533
TI  - Rhinomaxillary mucormycosis with palatal perforation: a case report.
AB  - Mucormycosis are a group of invasive infections caused by filamentous fungi of
      the Mucoraceae family. Mucormycosis is essentially limited to immunocompromised
      patients with poorly controlled diabetes mellitus, hematologic malignancy, organ
      transplant, chemotherapy, chronic renal insufficiency, malnutrition, deferoxamine
      therapy and severe burns. The fungi invade arteries leading to thrombosis that
      subsequently causes necrosis of hard and soft tissues. Here, we present a case
      report of a 50-year-old diabetic patient with rhinomaxillary form of
      mucormycosis. 

PMID- 25386534
TI  - An infiltrative angioarchitectural variant of arteriovenous malformation of
      temporalis.
AB  - Vascular anomalies of the head and neck region pose a certain diagnostic and
      therapeutic paradox. Management of arteriovenous malformations (AVM) is a
      challenge owing to the presence of abnormal vascular communications and high
      recurrence. We report a case of a 19-year-old male patient, who presented with
      diffuse swelling in the right temporal region. Magnetic Resonance Angiography
      (MRA) suggested it to be an AVM in the temporalis muscle, having afferents in the
      ascending pharyngeal artery, with cavernous angioma. Surgical excision of the
      lesion was carried out under carotid control. Histopathology of the excised
      specimen utilizing special stains confirmed the presence of AVM. An absence of
      distinct nidus concomitant along with the exuberant proliferation of capillaries
      between the muscle fibres suggested it be an infiltrative angioarchitectural
      variant. The present case highlights significance of diagnosing AVM in temporalis
      muscle which is a rare occurrence in head and neck region. Also, the importance
      of ruling out other closely resembling vascular diathesis, both non neoplastic
      and malignant is discussed. 

PMID- 25386535
TI  - Single anterior tooth replacement by a cast lingual loop connector - a
      conservative approach.
AB  - One of the most challenging and complex treatment modality is replacement of
      single anterior tooth. This can be overcome by different treatment options such
      as implant-supported restorations as well as conventional porcelain-fused-to
      metal and resin-bonded fixed partial dentures. Drifting of teeth into the
      edentulous area may reduce the available pontic space; whereas a diastema
      existing before an extraction may result in excessive mesiodistal dimension to
      the pontic space. Loop connector fixed partial denture (FPD) may be the simplest
      and best solution to maintain the diastema and provide optimum restoration of
      aesthetics. This article describes the procedure for the fabrication of a loop
      connector FPD to restore an excessively wide anterior edentulous space in a
      patient with existing spacing between the maxillary anterior teeth. 

PMID- 25386536
TI  - Dedifferentiated chondrosarcoma of temporomandibular joint: atypical features of
      a rare case.
AB  - Chondrosarcoma (CS) is an uncommon malignant mesenchymal tumour showing
      cartilaginous differentiation which rarely presents in the jaws. CS represents 10
      20% of all malignant bone tumours and less than 5% of tumours in head and neck
      region. Among the infrequent subtypes of CS, dedifferentiated CS is a sinister
      variant that presents with singular features and has extremely poor prognosis. We
      report a unique case of dedifferentiated CS that presented in the
      temporomandibular joint (TMJ) with extra articular involvement of the
      infratemporal space. This high grade CS is reviewed due to its rarity and the
      dentist is implored to take this variant into account when considering the
      differential diagnosis of destructive TMJ lesions. 

PMID- 25386537
TI  - Lymphangioma of the tongue - a case report and review of literature.
AB  - Lymphangiomas are benign tumours resulting from a congenital malformation of the
      lymphatic system. They are relatively uncommon and usually diagnosed in infancy
      and early childhood. Commonly located at head and neck, they rarely occur in the
      oral cavity. Intraoral lymphangiomas occur more frequently on the dorsum of
      tongue, followed by palate, buccal mucosa, gingiva, and lips. Lymphangioma of the
      tongue is a common cause of macroglossia in children associated with difficulty
      in swallowing and mastication, speech disturbances, airway obstruction,
      mandibular prognathism, openbite and other possible deformities of maxillofacial
      structures. We present the case of a 13-year-old female with lymphangioma of
      tongue. The clinical, radiological, and treatment modalities of this case are
      discussed. 

PMID- 25386538
TI  - A prosthodontic management of severely resorbed anterior ridge defect - a case
      report.
AB  - The Dental profession has devoted most of its history to restoring the effects of
      dental disease. The public's interest in Dental health and beauty has become an
      engine that continues to drive the demand for cosmetic dental procedures. In the
      past, achieving a beautiful smile required submission to extensive invasive
      procedures and expensive fixed dental prosthetic restorations. Advancements in
      restorative material formulations and adhesive technology have expanded such
      possibilities. Despite many recent advances in aesthetic dentistry techniques and
      materials, certain cases remain difficult to restore. Replacing missing anterior
      teeth presents a serious challenge to the clinicians especially with a large
      ridge defect. Such cases require not only replacement of the missing teeth but
      also the restoration of the bone defect, aesthetics and phonetics. While the
      conventional treatment approaches like fixed partial denture or an option of
      implant may not justify the restoration of the defects. A combination of fixed
      and removable restoration provides good alternative. The aim and purpose of this
      case report is to describe a multidisciplinary approach of managing a patient who
      reported with a similar complaint of missing anterior teeth with anterior ridge
      defect hoping to get not only her teeth but also her lost smile. 

PMID- 25386539
TI  - Restoring the Lost Functional Harmony in a Mutilated Dentition using Hobo's Twin
      Stage Concept of Full Mouth Rehabilitation.
AB  - Reorganization of an occlusion in a mutilated dentition is the most challenging
      task which is ever faced by prosthodontists. An occlusal rehabilitation, though
      it is common, is the most complex treatment procedure which is widely practised
      in treating severely worn out dentitions, developmental anomalies, acquired
      defects, ill fitting, long span fixed partial dentures and TMJ disorders. Various
      factors such as vertical dimension of occlusion, centric relation, occlusal
      contact pattern, aesthetics and phonetics need to be considered simultaneously
      for both anterior and posterior teeth during occlusal rehabilitations. Different
      schools of thoughts have been documented for rehabilitation of such cases and the
      choice of the treatment plan depends on the skill and experience of the
      clinician. This clinical report describes the full mouth rehabilitation of a
      severely worn out dentition, in functional harmony with the stomatognathic
      system. Hobo's Twin-stage procedure was adopted to produce a definite amount of
      disocclusion during eccentric movements. 

PMID- 25386540
TI  - Electrocautery assisted harvesting of free gingival graft to increase the width
      of attached gingiva - an uncommon case report.
AB  - Procuring a free gingival autograft for the purpose of gingival augmentation has
      been advocated in areas of inadequate width of attached gingiva that result in
      gingival recession and/or accumulation of local factors. As obtaining the graft
      from the palatal donor site with conventional scalpel techniques can result in
      problems such as prolonged bleeding, increased surgical time and patient
      discomfort, alternative methods have been advocated to procure such grafts using
      lasers and electrocautery. This case report elaborates, a free gingival graft
      harvested for the purpose of increasing the width of attached gingiva using
      electrocautery principles. The parameters assessed included the extent of patient
      reported discomfort at the donor site and clinical gain of keratinized and
      attached gingival width. 

PMID- 25386541
TI  - Parry-romberg syndrome: a case of late onset with rapid progression.
AB  - Parry-Romberg syndrome (PRS) or progressive hemifacial atrophy is rare, poorly
      understood condition with an unclear aetiology and characterized by slow and
      progressive atrophy affecting one side of the face. PRS is a syndrome with
      diverse presentation and the most common early sign is a painless cleft, the
      "coup de sabre" near the midline of the face which marks the boundary between the
      normal and atrophic tissues. Characteristically, the atrophy starts in the first
      decade of life and progresses slowly for several years before it becomes
      quiescent. This article describes a case of PRS in a 19-year-old female patient
      affecting the right side of the face which is unique in the fact that it had a
      late onset with rapid progression. 

PMID- 25386542
TI  - Revascularization of immature mandibular premolar with pulpal necrosis - a case
      report.
AB  - This case report describes the Revascularization of a Permanent Immature
      Mandibular Premolar with Pulp Necrosis and apical periodontitis. Access opening
      was done & the canal was disinfected with copious irrigation using 2.5% NaOCl and
      triple antibiotic paste (Ciprofloxacin, Metronidazole, and Minocycline) as
      intracanal medicament. After the disinfection protocol is complete, it is
      followed by revascularization procedure. The apex was mechanically irritated to
      initiate bleeding into the canal to produce a blood clot to the level just below
      the level of cementoenamel junction. Mineral trioxide aggregate was placed over
      the blood clot followed by bonded resin restoration above it. After one year
      follow up; the patient was asymptomatic, no sinus tract was evident. Apical
      periodontitis was resolved, and there was radiographic evidence of continuing
      thickness of dentinal walls. 

PMID- 25386543
TI  - Management of Complicated Crown Fracture and Associated Impacted Mesiodens- Case
      Report with 3yrs Follow-up.
AB  - Mesiodens being the most common type of supernumerary tooth, usually results in
      malocclusion, poor aesthetics and cyst formation if it is not corrected. The
      management protocol involves surgical removal. The situation can be complicated
      in young permanent dentition where there are a lot of chances of damage to the
      permanent dentition during surgical removal of impacted teeth. This article
      reports a case of impacted mesiodens which was diagnosed during management of
      complicated crown fracture. The case was followed up to 3years which showed a
      good bone formation. The article highlights the need for regular follow-up after
      surgical removal of impacted teeth in young children, to see any changes or
      damage in the developing permanent teeth. 

PMID- 25386544
TI  - Complete occlusal rehabilitation of patient with radiation caries - a case
      report.
AB  - One of the most distressing and dramatic causes of xerostomia is radiotherapy for
      the cure of maxillofacial and neck carcinomas. Patient with radiotherapy induced
      xerostomia presents with challenges in prosthodontic management and in unique
      radiation caries control. This clinical report illustrates step by step execution
      of complex treatment planning that lead to successful outcome in 34-year-old man,
      who had been treated with Radical Neck Dissection (RND) and therapeutic
      radiotherapy for squamous cell carcinoma of tongue and due to radiation caries,
      was presented with chief complaint of difficulty in mastication. Rehabilitation
      was carried out with metal-ceramic fixed restorations and cast removable
      prostheses after extensive endodontic intervention. This article also discusses
      the maintenance strategies for radiation caries patient requiring complete
      occlusal reconstruction, who certainly presents with special needs in post
      treatment management. 

PMID- 25386545
TI  - Warthin's Tumour: A Case Report and Review on Pathogenesis and its Histological
      Subtypes.
AB  - Warthin's tumour/ Papillary cystadenoma lymphomatosum (PCL) constitutes a
      minority of salivary gland neoplasms and it is a monomorphic adenoma which
      primarily involves the parotid gland. Warthin's tumour shows multiple cysts that
      have numerous papillations covered by bilayered columnar and basaloid oncocytic
      epithelium. The connective tissue portion shows proliferation of follicle-
      containing lymphoid tissue which necessitates careful distinction for diagnosis.
      Although, Warthin's tumour presents as a clinically benign, slow-growing, usually
      asymptomatic lesion with low rates of recurrences and malignant transformation,
      but still this tumour is considered unique because of its histological appearance
      and unknown origin and pathogenesis. Here, we report a case of Warthin's tumour
      of five years duration in a 50-year-old male patient in the right parotid gland
      and also review and discuss various concepts concerning the development of this
      tumour along with a comprehensive literature on its clinic-pathologic features. 

PMID- 25386546
TI  - Extra corporeal fixation of fractured mandibular condyle.
AB  - Condylar fracture is the second most common site in the mandibular fractures.
      Motor vehicle accident and fall are the major causes of such fractures. Because
      of the anatomical weakness of the condyle and the shape of the condylar head the
      antero-medial dislocation of the condyle is common. Open reduction and closed
      reduction is always debatable. The open reduction will bring back the normal
      function much earlier than closed reduction. Medially dislocated condylar
      fracture fragments are always managed with open method. In superior or high
      condylar fractures,exact reduction with conventional open reduction can be
      difficult due to the limited surgical and visual fields. In such cases
      extracorporeal fixation of condyle using vertical ramus osteotomy may be better
      choice to achieve perfect alignment and absolute maintaince of vertical height of
      the ramus and facial symmetry. We here present a case of extracorporeal fixation
      of unilateral left high condylar fracture. 

PMID- 25386547
TI  - Surgical margins and its evaluation in oral cancer: a review.
AB  - The main surgical goal while treating cancer is to remove all local malignant
      disease with no residual malignant cells left. Overall benefits of achieving
      negative resection margins in terms of disease free local recurrence and overall
      survival has been discussed in many studies. The quantity of normal tissue to be
      removed during surgical procedure has not been standardised. Local recurrence can
      also occur among tumours with extensive histological demonstration of adequate
      resection margins. Oral cavity, submandibular region, tonsil and pharynx are the
      sites which have high chances of recurrence, even after showing negative margins.
      Therefore, the current approaches for histological risk assessment and various
      methods of evaluation of the surgical margins with their limitations are briefed
      in the present article. 

PMID- 25386548
TI  - Enamel regeneration - current progress and challenges.
AB  - Dental Enamel is the outermost covering of teeth. It is hardest mineralized
      tissue present in the human body. Enamel faces the challenge of maintaining its
      integrity in a constant demineralization and remineralization within the oral
      environment and it is vulnerable to wear, damage, and decay. It cannot regenerate
      itself, because it is formed by a layer of cells that are lost after the tooth
      eruption. Conventional treatment relies on synthetic materials to restore lost
      enamel that cannot mimic natural enamel. With advances in material science and
      understanding of basic principles of organic matrix mediated mineralization paves
      a way for formation of synthetic enamel. The knowledge of enamel formation and
      understanding of protein interactions and their gene products function along with
      the isolation of postnatal stem cells from various sources in the oral cavity,
      and the development of smart materials for cell and growth factor delivery, makes
      possibility for biological based enamel regeneration. This article will review
      the recent endeavor on biomimetic synthesis and cell based strategies for enamel
      regeneration. 

PMID- 25386549
TI  - Social capital and oral health.
AB  - Social determinants have always been an important element of the oral health. It
      has been seen that social aspects like the organizations and relations influence
      the health of population. A new domain named social capital has come up into
      limelight which refers to "features of social organization, such as trust, norms
      and networks that can improve the efficacy of society by facilitating coordinated
      actions". The bonds between individuals, both in intimate relationships and in
      voluntary associations have been claimed to have health promoting effects. Oral
      health can never be segregated from general health as they are bidirectional in
      their relationship. Therefore determinants of general health and its promotion
      are interlinked with that of oral health. So, this review tries to figure out the
      effects of social capital on various aspects of oral health. 

PMID- 25386550
TI  - Drug induced erythema multiforme: two case series with review of literature.
AB  - Erythema Multiforme, (EM) an uncommon, acute inflammatory reactive mucocutaneous
      disorder and primary allergies confined to the oral mucosa. However the
      subsequent attacks can produce more severe forms of EM involving the skin.
      Manifestations of EM are varied and present a diagnostic dilemma because
      infections (particularly herpes simplex and mycoplasma pneumoniae) and drugs seem
      to predispose towards development of EM. We report two cases of EM in which drugs
      (Dioclofenac sodium & Amoxycilline) seems to be precipitating factor. In
      addition, the article reviews various aspects of EM as relevant to dental
      practice and highlight the associated potential etiologic agents, pathogenic
      mechanisms and therapies. 

PMID- 25386551
TI  - Ameloblastoma variant.

PMID- 25386552
TI  - Intellectual and developmental disabilities: male health.

PMID- 25386554
TI  - Significance of population health knowledge in the education of the undergraduate
      workforce for careers in the health care sector.

PMID- 25386553
TI  - Colorectal cancer screening: tests, strategies, and perspectives.
AB  - Screening has a central role in colorectal cancer (CRC) control. Different
      screening tests are effective in reducing CRC-specific mortality. Influence on
      cancer incidence depends on test sensitivity for pre-malignant lesions, ranging
      from almost no influence for guaiac-based fecal occult blood testing (gFOBT) to
      an estimated reduction of 66-90% for colonoscopy. Screening tests detect lesions
      indirectly in the stool [gFOBT, fecal immunochemical testing (FIT), and fecal
      DNA] or directly by colonic inspection [flexible sigmoidoscopy, colonoscopy, CT
      colonography (CTC), and capsule endoscopy]. CRC screening is cost-effective
      compared to no screening but no screening strategy is clearly better than the
      others. Stool tests are the most widely used in worldwide screening
      interventions. FIT will soon replace gFOBT. The use of colonoscopy as a screening
      test is increasing and this strategy has superseded all alternatives in the US
      and Germany. Despite its undisputed importance, CRC screening is under-used and
      participation rarely reaches 70% of target population. Strategies to increase
      participation include ensuring recommendation by physicians, introducing
      organized screening and developing new, more acceptable tests. Available evidence
      for DNA fecal testing, CTC, and capsule endoscopy is reviewed. 

PMID- 25386555
TI  - Recent advances in carbon nanotube-based enzymatic fuel cells.
AB  - This review summarizes recent trends in the field of enzymatic fuel cells. Thanks
      to the high specificity of enzymes, biofuel cells can generate electrical energy
      by oxidation of a targeted fuel (sugars, alcohols, or hydrogen) at the anode and
      reduction of oxidants (O2, H2O2) at the cathode in complex media. The combination
      of carbon nanotubes (CNT), enzymes and redox mediators was widely exploited to
      develop biofuel cells since the electrons involved in the bio-electrocatalytic
      processes can be efficiently transferred from or to an external circuit. Original
      approaches to construct electron transfer based CNT-bioelectrodes and impressive
      biofuel cell performances are reported as well as biomedical applications. 

PMID- 25386556
TI  - Genomic Changes in an Attenuated ZB Strain of Foot-and-Mouth Disease Virus
      Serotype Asia1 and Comparison with Its Virulent Parental Strain.
AB  - The molecular basis of attenuation of foot-and-mouth disease virus (FMDV)
      serotype Asia1 ZB strain remains unknown. To understand the genetic changes of
      attenuation, we compared the entire genomes of three different rabbit-passaged
      attenuated ZB strains (ZB/CHA/58(att), ZBRF168, and ZBRF188) and their virulent
      parental strains (ZBCF22 and YNBS/58). The results showed that attenuation may be
      brought about by 28 common amino acid substitutions in the coding region, with
      one nucleotide point mutation in the 5'-untranslated region (5'-UTR) and another
      one in the 3'-UTR. In addition, a total of 21 nucleotides silent mutations had
      been found after attenuation. These substitutions, alone or in combination, may
      be responsible for the attenuated phenotype of the ZB strain in cattle. This will
      contribute to elucidation of attenuating molecular basis of the FMDV ZB strain. 

PMID- 25386557
TI  - Downregulation of MDR1 gene by cepharanthine hydrochloride is related to the
      activation of c-Jun/JNK in K562/ADR cells.
AB  - The purpose of the study was to determine the signal transduction mechanism of
      cepharanthine hydrochloride (CH) on reversing tumor multidrug resistance. RT-PCR
      and Western blot analysis were used to determine the effects of CH on the
      expression of MDR1 mRNA and P-glycoprotein in K562/ADR cells when CH was used
      alone and combined with SP600125, a JNK inhibitor, to explore the effects of CH
      on JNK pathway. Western blot analysis was used to determine the effects of CH on
      c-Jun protein expression and phosphorylation, to explore the regulating effects
      of CH on c-Jun and phosphorylated c-Jun (p-c-Jun) proteins. Our results showed
      that the inhibitory effect of CH on MDR1 mRNA increased with the concentrations
      of CH (5.0, 10.0, and 20.0 MUM) and the inhibitory effects of CH on MDR1 mRNA and
      P-glycoprotein increased with the incubation time of CH (0, 12, 24, 36, and 48
      hours). The inhibitory effect was weakened after CH combined with SP600125. The
      expressions of c-Jun and p-c-Jun proteins increased with the incubation time of
      CH (0, 6, 12, and 24 hours). These findings suggest that CH downregulated the
      expressions of MDR1 mRNA and P-glycoprotein in a time and concentration manner;
      the mechanism may be mediated via activating c-Jun/JNK pathway. 

PMID- 25386558
TI  - Genetic multipartitions based on D-Loop sequences and chromosomal patterns in
      brown chromis, Chromis multilineata (Pomacentridae), in the Western Atlantic.
AB  - Connectivity levels among Brazilian reef fish fauna populations have attracted
      growing interest, mainly between mainland shores and oceanic islands. The
      Pomacentridae, whose phylogeographic patterns are largely unknown in the
      Atlantic, are a family of dominant fish in reef regions. We present data on the
      variability and population structure of damselfish Chromis multilineata in
      different areas along the northeast coast of Brazil and in the waters around the
      oceanic islands of Fernando de Noronha (FNA) and Saint Peter and Saint Paul
      Archipelago (SPSPA) through analysis of the HVR1 mtDNA sequence of the control
      region. The remote SPSPA exhibits the highest level of genetic divergence among
      populations. Conventional and molecular cytogenetic analysis showed similar
      karyotype patterns (2n=48 acrocentrics) between these insular areas. Our
      estimates reveal three genetically different population groups of C. multilineata
      on the Brazilian coast. The level of genetic structure is higher than previous
      data suggested, indicating complex panel of interactions between the oceanic
      island and coastal populations of Brazil.

PMID- 25386559
TI  - Deregulation of serum microRNA expression is associated with cigarette smoking
      and lung cancer.
AB  - Lung cancer is the leading cause of cancer-related death and cigarette smoking is
      the main risk factor for lung cancer. Circulating microRNAs (miRNAs) are
      considered potential biomarkers of various cancers, including lung cancer.
      However, it is unclear whether changes in circulating miRNAs are associated with
      smoking and smoking-related lung cancer. In this study, we determined the serum
      miRNA profiles of 10 nonsmokers, 10 smokers, and 10 lung-cancer patients with
      miRCURY LNA microRNA arrays. The differentially expressed miRNAs were then
      confirmed in a larger sample. We found that let-7i-3p and miR-154-5p were
      significantly downregulated in the sera of smokers and lung-cancer patients, so
      the serum levels of let-7i-3p and miR-154-5p are associated with smoking and
      smoking-related lung cancer. The areas under receiver operating characteristic
      curves for let-7i-3p and miR-154-5p were approximately 0.892 and 0.957,
      respectively. In conclusion, our results indicate that changes in serum miRNAs
      are associated with cigarette smoking and lung cancer and that let-7i-3p and miR
      154-5p are potential biomarkers of smoking-related lung cancer. 

PMID- 25386561
TI  - Contribution of alpha,beta-Amyrenone to the Anti-Inflammatory and
      Antihypersensitivity Effects of Aleurites moluccana (L.) Willd.
AB  - The aim of the study was to analyze the constituents of the dichloromethane
      fraction obtained from A. moluccana and also to evaluate the anti-inflammatory
      and antinociceptive properties of alpha,beta-amyrenone isolated from A. moluccana
      in mice. The dichloromethane fraction was evaluated by gas chromatography and
      submitted to purification. The mixture of alpha,beta-amyrenone was isolated and
      then evaluated using the carrageenan-induced paw-oedema or pleurisy and CFA
      induced arthritis models in mice. Five triterpenes, alpha,beta-amyrenone,
      glutinol, and alpha,beta-amyrin were isolated from dichloromethane fraction of A.
      moluccana leaf extract. The mixture of alpha,beta-amyrenone, dosed orally, was
      able to reduce mechanical hypersensitivity and paw-oedema induced by carrageenan,
      interfering with neutrophil migration. Similar results were observed in the
      carrageenan-induced pleurisy model. Repeated administration of the compounds was
      also effective in reducing the mechanical sensitization and oedema developed in
      the arthritis model induced by CFA. In conclusion, the results demonstrate that
      alpha,beta-amyrenone interferes in both acute and chronic inflammatory processes.
      We can infer that these effects involve, at least in part, a reduction in the
      neutrophil migration. Therefore, it seems reasonable to suggest that alpha,beta
      amyrenone could represent a new therapeutic tool for the management of painful
      and inflammatory diseases, especially those presenting a chronic profile. 

PMID- 25386562
TI  - Serum fetuin-A levels in patients with cardiovascular disease: a meta-analysis.
AB  - BACKGROUND: Fetuin-A (FA) suppresses arterial calcification, promotes insulin
      resistance, and appears to be elevated in patients with cardiovascular diseases
      (CVD), but the data is still inconsistent. To clarify the correlation between
      serum FA levels and the presence and severity of CVDs, we performed this meta
      analysis. METHOD: Potential relevant studies were identified covering the
      following databases: PubMed, Embase, Web of Science, Cochrane Library, CISCOM,
      CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge
      Infrastructure (CNKI) databases. Data from eligible studies were extracted and
      included in the meta-analysis using a random-effects model. RESULTS: Ten case
      control studies, including 1,281 patients with CVDs and 2,663 healthy controls,
      were included. The results showed significant differences in serum levels of FA
      between the CVDs patients and the healthy controls (SMD=1.36, 95%CI: 0.37-2.36,
      P=0.007). Ethnicity-subgroup analysis implied that low serum FA levels are
      related to CVDs in Caucasians (SMD=1.73, 95%CI: 0.20-3.26, P=0.026), but not in
      Asians (SMD=1.04, 95%CI: -0.33-2.40, P=0.138). CONCLUSION: The data indicated
      that decreased serum FA level is correlated with the development of CVDs. FA
      might be clinically valuable for reflecting the progression of CVDs.

PMID- 25386560
TI  - Molecular chaperone dysfunction in neurodegenerative diseases and effects of
      curcumin.
AB  - The intra- and extracellular accumulation of misfolded and aggregated amyloid
      proteins is a common feature in several neurodegenerative diseases, which is
      thought to play a major role in disease severity and progression. The principal
      machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal
      autophagy systems, where heat shock proteins play a crucial role. Many protein
      aggregates are degraded by the lysosomes, depending on aggregate size, peptide
      sequence, and degree of misfolding, while others are selectively tagged for
      removal by heat shock proteins and degraded by either the proteasome or
      phagosomes. These systems are compromised in different neurodegenerative
      diseases. Therefore, developing novel targets and classes of therapeutic drugs,
      which can reduce aggregates and maintain proteostasis in the brains of
      neurodegenerative models, is vital. Natural products that can modulate heat shock
      proteins/proteosomal pathway are considered promising for treating
      neurodegenerative diseases. Here we discuss the current knowledge on the role of
      HSPs in protein misfolding diseases and knowledge gained from animal models of
      Alzheimer's disease, tauopathies, and Huntington's diseases. Further, we discuss
      the emerging treatment regimens for these diseases using natural products, like
      curcumin, which can augment expression or function of heat shock proteins in the
      cell. 

PMID- 25386563
TI  - Renal protective effect of sirtuin 1.
AB  - Silent information regulator 2 (Sir2) is a nicotinamide adenine dinucleotide-
      (NAD(+)-) dependent deacetylase. The homology of SIRT1 and Sir2 has been
      extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD(+)
      and is therefore linked to cellular energy metabolism and the redox state through
      multiple signalling and survival pathways. During the past decade, investigators
      have reported that SIRT1 activity is essential in cancer, neurodegenerative
      diseases, diabetes, cardiovascular disease, and other age-related diseases. In
      the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation, and fibrosis.
      Therefore its activation may also become a new therapeutic target in the patients
      with chronic kidney disease including diabetic nephropathy. In this paper, we
      would like to review the protective functions of sirtuins and the role of SIRT1
      in the onset of kidney disease based on previous studies, including diabetic
      nephropathy, acute renal injury, chronic kidney disease as well as lupus
      nephritis. 

PMID- 25386564
TI  - Protective effects of baicalin on decidua cells of LPS-induced mice abortion.
AB  - The study was carried out to investigate the protective effects of Baicalin on
      decidual cells of LPS-induced abortion mice. In the in vitro experiment, the
      decidual cells were cultured by uterus tissue mass cultivation sampled at day 6
      of pregnancy, and gradient concentrations of LPS were used to determine the
      optimal LPS concentration of the injured decidual cells model. The injured
      decidual cells were treated with Baicalin (4 MUg/mL) to determine the protective
      role of Baicalin. In the in vivo experiment, lipopolysaccharide (LPS) was
      injected intravenously via the tail vein to induce abortion at day 6 of
      pregnancy, and the mice were given different concentrations of Baicalin by oral
      gavage consecutively at days 7 to 8 of pregnancy. On day 9 of gestation, the mice
      were sacrificed. The TNF and progesterone contents in the serum were assayed by
      ELISA. The results clearly revealed that Baicalin can prevent the injury to
      decidual cells from LPS dose dependently, TNF was decreased significantly (P <
      0.01) compared to LPS group, and there was no effect on the progesterone. These
      findings suggest that Baicalin has protective effects on the injured decidual
      cells in the pregnant mice.

PMID- 25386565
TI  - Cognitive Functioning in Adults Aging with HIV: A Cross-Sectional Analysis of
      Cognitive Subtypes and Influential Factors.
AB  - OBJECTIVE: This cross-sectional study examined cognitive subtypes and influential
      factors in HIV-positive (HIV+) adults. METHOD: Two-step cluster analysis was
      conducted on a neurocognitive test battery in a sample (N = 78) of adults and
      older adults with HIV (Mage = 46.1). Next, cognitive, functional, and mental and
      physical health differences were compared between the HIV+ clusters and an HIV-
      reference group (N = 84; Mage = 47.9). RESULTS: A two-cluster solution emerged,
      with a lower performing cluster exhibiting poorer performance across all domains
      except psychomotor speed, and a "normal" cluster displaying similar performance
      as the HIV- group. The most influential factors to classification in the lower
      performing cluster were older age and presence of stroke and hypertension. There
      were trends for longer duration of HIV-infection, higher unemployment rates, and
      greater prevalence of Hepatitis C co-infection in the lower performing cluster.
      CONCLUSIONS: These findings suggest that there are not unique cognitive subtypes
      in HIV, but rather a subset of individuals who exhibit globally normal
      performance and those with below average performance. Older age and the related
      cardiovascular comorbidities of both aging and HIV medications may be key
      influential factors to variability in neurocognitive functioning in this
      population and thus should be considered in future studies. Implications for
      research and practice are provided.

PMID- 25386566
TI  - Transport of gold nanoparticles through plasmodesmata and precipitation of gold
      ions in woody poplar.
AB  - Poplar plants (Populus deltoides * nigra, DN-34) were used as a model to explore
      vegetative uptake of commercially available gold nanoparticles (AuNPs) and their
      subsequent translocation and transport into plant cells. AuNPs were directly
      taken up and translocated from hydroponic solution to poplar roots, stems and
      leaves. Total gold concentrations in leaves of plants treated with 15, 25 and 50
      nm AuNPs at exposure concentrations of 498+/-50.5, 247+/-94.5 and 263+/-157 ng/mL
      in solutions were: 0.023+/-0.006, 0.0218+/-0.004 and 0.005+/-0.0003 ug/g dry
      weight, respectively, which accounted for 0.05, 0.10 and 0.03%, respectively, of
      the total gold mass added. The presence of total gold in plant tissues was
      measured by inductively coupled plasma mass spectrometry, while AuNPs were
      observed by transmission electron microscopy in plant tissues. In solution, AuNPs
      were distinguished from Au(III) ions by membrane separation and centrifugation.
      AuNPs behaved conservatively inside the plants and were not dissolved into gold
      ions. On the other hand, Au(III) ions were taken up and reduced into AuNPs inside
      whole plants. AuNPs were observed in the cytoplasm and various organelles of root
      and leaf cells. A distinct change in color from yellow to pink was observed as
      Au(III) ions were reduced and precipitated in hydroponic solution. The
      accumulation of AuNPs in the plasmodesma of the phloem complex in root cells
      clearly suggests ease of transport between cells and translocation throughout the
      whole plant, inferring the potential for entry and transfer in food webs.

PMID- 25386567
TI  - Langerhans cell activation in diabetic small fiber polyneuropathy.

PMID- 25386568
TI  - Greetings from the editor.

PMID- 25386569
TI  - Biopsy in musculoskeletal tumors.

PMID- 25386570
TI  - Reconstruction of the Acetabulum in Developmental Dysplasia of the Hip in total
      hip replacement.
AB  - Developmental dysplasia of the hip (DDH) or congenital hip dysplasia (CDH) is the
      most prevalent developmental childhood hip disorder. It includes a wide spectrum
      of hip abnormalities ranging from dysplasia to subluxation and complete
      dislocation of the hip joint. The natural history of neglected DDH in adults is
      highly variable. The mean age of onset of symptoms is 34.5 years for dysplastic
      DDH, 32.5 years for low dislocation, 31.2 years for high dislocation with a false
      acetabulum, and 46.4 years for high dislocation without a false acetabulum.
      Thorough understanding of the bony and soft tissue deformities induced by
      dysplasia is crucial for the success of total hip arthroplasty. It is important
      to evaluate the existing acetabular deformity three-dimensionally, and customize
      the correction in accordance with the quantity and location of ace tabular
      deficiencies. Acetabular reconstruction in patients with DDH is challenging.
      Interpretation of published data is difficult and should be done with caution
      because most series include patients with different types of hip disease. In
      general, the complication rate associated with THA is higher in patients with hip
      dysplasia than it is in patients with osteoarthritis. Overall, clinical and
      functional outcomes following THA in patients hip dysplasia (DDH) differ from
      those treated for primary hip osteoarthritis, possibly due to the lower age and
      level of activity. Although function scores decline with age, the scores for pain
      and range of motion presented with a statistically significant improvement in the
      long-term. 

PMID- 25386571
TI  - Medial Unicompartmental Osteoarthritis (MUO) of the Knee: Unicompartmental Knee
      Replacement (UKR) or Total Knee Replacement (TKR).
AB  - The aim of this review article is to analyze the clinical effectiveness of total
      knee replacement (TKR) compared to unicompartmental knee replacement (UKR) in
      patients with medial unicompartmental osteoarthritis (MUO) in terms of survival
      rates, revision rates and postoperative complications. The search engine was
      MedLine. The keywords used were: medial knee osteoarthritis. Three thousand and
      ninety-six articles were found on 28 April 2014. Of those, only twenty-eight were
      selected and reviewed because they were strictly focused on the topic of this
      article. Compared with those who have TKR, patients who undergo UKR have higher
      revision rates and lower survival rates at 5, 10 and 15 years. The reported
      overall risk of postoperative complications for patients undergoing TKR is 11%,
      compared with 4.3% for patients undergoing UKR. In conclusion, UKR have higher
      revision rates and lower survival rates than TKR. There is, however, an increased
      risk of postoperative complications after TKR. 

PMID- 25386572
TI  - Intraarticular Administration of Tranexamic Acid Following Total Knee
      Arthroplasty: A Case-control Study.
AB  - BACKGROUND: Tranexamic acid (TXA) has received extensive attention in management
      of blood loss in orthopedic surgeries. However, the ideal method of TXA
      administration is still controversial. This study aims to determine whether
      intraarticular injection of TXA reduces blood loss after total knee arthroplasty
      (TKA). METHODS: Through a retrospective case-control study consecutive TKA
      patients receiving intraarticular TXA (Case group) were compared with similar
      patients undergoing TKA using traditional blood management strategy (Control
      group). Hemoglobin levels (Hb) before and after the surgery, need for
      transfusion, and reoperation due to massive blood loss were compared between the
      two groups. RESULTS: Fifty TXA patients were compared with 50 patients of the
      control group. There was no significant difference between the two groups in
      terms of age, gender, and preoperative Hb. Postoperative blood loss and
      transfusion rate were significantly reducedin TXA patients compared to the
      control group (P<0.05). CONCLUSIONS: Our study revealed that intraarticular
      administration of TXA reduces postoperative blood loss as well as need for blood
      transfusion in patients undergoing TKA.

PMID- 25386573
TI  - Soluble mediators in posttraumatic wrist and primary knee osteoarthritis.
AB  - BACKGROUND: New discoveries about the pathophysiology changed the concept that
      all forms of osteoarthritis are alike; this lead to the delineation of different
      phenotypes such as age, trauma or obese related forms. We aim to compare soluble
      mediator profiles in primary knee and posttraumatic wrist osteoarthritis. Based
      on the general faster progression rate of wrist osteoarthritis, we hypothesize a
      more inflammatory profile. METHODS: We collected synovial fluid from 20 primary
      osteoarthritic knee and 20 posttraumatic osteoarthritic wrist joints. 17
      mediators were measured by multiplex enzyme-linked immunosorbent assay: chemokine
      ligand 5, interferon-gamma, leukemia inhibitory factor, oncostatin-M,
      osteoprotegerin, tumor necrosis factor-alpha, vascular endothelial growth factor,
      interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-7, IL
      8, IL-10, IL-13 and IL-17. RESULTS: TEN MEDIATORS WERE HIGHER IN POSTTRAUMATIC
      OSTEOARTHRITIC SYNOVIAL FLUID: tumor necrosis factor-alpha (TNFalpha), IL-1alpha,
      IL-1RA, IL-6, IL-10, IL-17, oncostatin-M, interferon-gamma, chemokine ligand 5
      and leukemia inhibitory factor (P<0.001). IL-1beta, IL-4, IL-7 were not detected,
      TNFalpha was not detected in knee osteoarthritic synovial fluid. IL-8, IL-13,
      osteoprotegerin and vascular endothelial growth factor levels did not differ
      between the synovial fluid types. CONCLUSIONS: In general wrist osteoarthritis
      seems characterized by a stronger inflammatory response than primary knee
      osteoarthritis. More pronounced inflammatory mediators might offer a paradigm for
      the faster progression of posttraumatic osteoarthritis. Increase of specific
      mediators could form a possible target for future mediator modulating therapy in
      wrist osteoarthritis.

PMID- 25386574
TI  - In-Hospital Outcomes after Hemiarthroplasty versus Total Hip Arthroplasty for
      Isolated Femoral Neck Fractures.
AB  - BACKGROUND: Previous studies suggest total hip arthroplasty may have some
      benefits compared to hemi-arthroplasty for displaced intracapsular femoral neck
      fractures in patients more than 60 years of age. The primary research question of
      our study was whether in-hospital adverse events, post-operative length of stay
      (LOS) and mortality in patients 60 year of age or older differed between total
      hip and hemi-arthroplasty for femoral neck fracture. METHODS: We obtained data on
      82951 patients more than 60 years of age with an isolated femoral neck fracture
      treated with either hemi-arthroplasty or total hip arthroplasty in 2009 or 2010
      from the National Hospital Discharge Survey (NHDS) database. The International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9, CM) was
      used to code diagnoses, comorbidities, complications, and procedures. RESULTS:
      Controlling for demographics and comorbidities, patients treated with hemi
      arthroplasty had a 40% (95% CI 1.4-1.5) higher risk of adverse events compared to
      patients treated with a total hip arthroplasty. Length of stay and in-hospital
      mortality did not differ between these groups. CONCLUSIONS: The observed
      advantage for total hip arthroplasty might reflect greater infirmity in hemi
      arthroplasty patients that was not accounted for by ICD-9 codes alone.

PMID- 25386575
TI  - Long Term Outcomes of Total Hip Arthroplasty in Young Patients under 30.
AB  - BACKGROUND: We aimed to report outcomes of total hip arthroplasty (THA) in very
      young patients under the year of 30. METHODS: Thirty patients (45 hips) with
      various indications for THA were retrospectively reviewed radiologically and
      clinically and analyzed regarding survival, reasons of failure, factors
      associated with outcomes and postoperative complications. RESULTS: Within a mean
      follow-up time of 116 months the 10-year survival rate was 90.3%. All hips were
      revised due to aseptic loosening. No association was found among the tested
      parameters with increased revision rates. Three complications associated with the
      THA were recorded and managed conservatively. All patients had statistically
      significant improved clinical scores compared to the pre-operative period,
      despite the underlying disorder that compromised the condition in the majority of
      the patients. CONCLUSIONS: Our study showed excellent long term outcomes of THA
      in patients younger than 30 years of age, comparable with those in older
      patients.

PMID- 25386576
TI  - Hemodynamic and Arterial Blood Gas Parameters during Cemented Hip
      Hemiarthroplasty in Elderly Patients.
AB  - BACKGROUND: Patients undergoing cemented hip hemiarthroplasty may develop bone
      cement implantation syndrome (BCIS) which is a leading cause of intraoperative
      complications. The purpose of this study was to evaluate cardiovascular changes
      during cemented hip hemiarthroplasty in elderly patients. METHODS: Cemented hip
      hemiarthroplasty was performed on 72 patients with femoral neck fracture. All
      patients were catheterized with a radial artery catheter to assess mean arterial
      pressure (MAP) and arterial blood gas (ABG) in these time points: just before
      cementation, just after cementation (0th), 5 min (5th) and 10 min (10th) after
      cementation, and at the end of surgery (END). Also, systolic and diastolic blood
      pressure (SBP & DBP), heart rate and any arrhythmia or cardiac arrest was
      evaluated. RESULTS: Seventy-two patients (33 females, 39 males; mean age: 66.8+/
      7 years) were evaluated. All parameters changed during cementation with a
      significant drop in MAP, SBP, and DBP immediately after cementation and pH and
      base excess decreased significantly (P<0.001) with no changes in O2 saturation.
      Mean heart rate rose until the 5th and then decreased dramatically with no
      bradycardia presentation. During cementation, 12 patients showed arrhythmia, but
      no cardiac-arrest was observed. CONCLUSIONS: Under strict observation of a
      anesthesiology care team, hemiarthroplasty can be a safe method for femoral neck
      fracture in elderly osteoporotic patients without severe cardiopulmonary
      compromise.

PMID- 25386577
TI  - Management of Hip Fractures in Lateral Position without a Fracture Table.
AB  - BACKGROUND: Hip fracture Management in supine position on a fracture table with
      biplane fluoroscopic views has some difficulties which leads to prolongation of
      surgery and increasing x- rays' dosage. The purpose of this study was to report
      the results and complications of hip fracture management in lateral position on a
      conventional operating table with just anteroposterior fluoroscopic view.
      METHODS: 40 hip fractures (31 trochanteric and 9 femoral neck fractures) were
      operated in lateral position between Feb 2006 and Oct 2012. Age, gender, fracture
      classification, operation time, intra-operation blood loss, reduction quality,
      and complications were extracted from patients' medical records. The mean follow
      up time was 30.78+/-22.73 months (range 4-83). RESULTS: The mean operation time
      was 76.50 +/- 16.88 min (range 50 - 120 min).The mean intra-operative blood loss
      was 628.75 +/- 275.00 ml (range 250-1300ml). Anatomic and acceptable reduction
      was observed in 95%of cases. The most important complications were malunion (one
      case in trochanteric group), avascular necrosis of femoral head and nonunion
      (each one case in femoral neck group). CONCLUSIONS: It sounds that reduction and
      fixation of hip fractures in lateral position with fluoroscopy in just
      anteroposterior view for small rural hospitals may be executable and probably
      safe.

PMID- 25386578
TI  - How to Treat the Complex Unstable Intertrochanteric Fractures in Elderly
      Patients? DHS or Arthroplasty.
AB  - BACKGROUND: Due to difficulty in obtaining anatomical reduction, management of
      the unstable intertrochanteric fractures in elderly osteoporotic patients is
      challenging. The purpose of this study is to compare the results of hip
      arthroplasty (total, hemi, or bipolar) with DHS in the elderly patients with
      unstable intertrochanteric fractures. METHODS: We prospectively studied and
      followed-up 80 old patients with complex unstable intertrochanteric fracture from
      January 2007 to December 2010. Depending on the time of the patients' admission,
      we alternatively treated them by DHS and arthroplasty, and placed them in Groups
      A and B, respectively. We followed them up radiologically and also clinically by
      Harris Hip Score for more than 24 months. Statistical analysis was performed
      using SPSS version 11.5 for Windows. RESULTS: The mean length of follow-up and
      age were 34.3+/-4.1 months (ranged; 24-59) and the 75.2+/-5.2 years (ranged; 58
      96), respectively. Comparing Group A with B, demographic data, mean blood loss,
      duration of operation, time to walking and duration of hospital stay had no
      significant difference but overall device related complications were
      significantly higher in Group A. Functional scores were also higher in Group B,
      but this difference was not significant statistically. In both groups, the
      patients with Type A3 compared with Type A2, had more duration of surgery and
      blood loss. CONCLUSIONS: Arthroplasty is an alternative treatment in elderly
      patients with unstable intertrochanteric fractures and can provide good and
      satisfactory clinical outcomes associated with low complication and mortality
      rates.

PMID- 25386579
TI  - Outcome Assessment after Aptis Distal Radioulnar Joint (DRUJ) Implant
      Arthroplasty.
AB  - BACKGROUND: Conventional treatments after complicated injuries of the distal
      radioulnar joint (DRUJ) such as Darrach and Kapandji-Sauve procedures have many
      drawbacks, which may eventually lead to a painful unstable distal ulna. The
      development of DRUJ prosthesis has significantly evolved over the past years. In
      this study, we assessed the outcome results of patients after DRUJ implant
      arthroplasty using the Aptis (Scheker) prosthesis. METHODS: We identified 13
      patients with 14 prosthesis during the past 10 years. Patients underwent DRUJ
      arthroplasty due to persistent symptoms of instability, chronic pain, and
      stiffness. Records and follow-up visits were reviewed to find the final post
      operative symptoms, pain, range of motion, and grip strength with a mean follow
      up of 12 months (range: 2-25 months). Also, patients were contacted prospectively
      by phone in order to administer the disabilities of the arm shoulder and hand
      (DASH), patient rated wrist evaluation (PRWE), and visual analogue scale (VAS),
      and to interview regarding satisfaction and progress in daily activities. Eleven
      patients out of 13 could be reached with a median follow-up time of 60 months
      (range: 2 to 102 months). RESULTS: No patient required removal of the prosthesis.
      Only two patients underwent secondary surgeries in which both required
      debridement of the screw tip over the radius. The median DASH score, PRWE score,
      VAS, and satisfaction were 1.3, 2.5, 0, and 10, respectively. The mean range of
      flexion, extension, supination, and pronation was 62, 54, 51, and 64,
      respectively. CONCLUSIONS: Distal radioulnar joint injuries are disabling and
      patients usually undergo one or more salvage surgeries prior to receiving an
      arthroplasty. The Scheker prosthesis has shown satisfactory results with 100%
      survival rate in all reports. The constrained design of this prosthesis gives
      enough stability to prevent painful subluxation.

PMID- 25386580
TI  - Progression of carpal tunnel syndrome according to electrodiagnostic testing in
      nonoperatively treated patients.
AB  - BACKGROUND: This study tested the null hypothesis that nonoperatively treated
      patients would not show disease progression of carpal tunnel syndrome (CTS) over
      time according to median nerve distal motor latency (DML) on two
      electrodiagnostic tests. METHODS: This retrospective study analyzed sixty-two
      adult nonoperatively treated patients who were diagnosed with CTS confirmed by a
      minimum of two electrodiagnostic tests at our institution between December 2006
      and October 2012. A Wilcoxon signed-rank test was conducted to test the
      difference between electrodiagnostic measurements between the first and last
      test. RESULTS: The mean time between the first and last electrodiagnostic test
      was 26+/-12 months (range, 12 to 55 months). The only electrodiagnostic
      measurement that increased significantly was the difference between median and
      ulnar DML on the same side (r=0.19, P=0.038). The time between the
      electrodiagnostic tests was significantly longer for patients with at least 10%
      worsening of the DML at the second test compared to cases of which the DML did
      not worsen or improve a minimum of 10% (P=0.015). CONCLUSIONS: There is evidence
      that-on average-idiopathic median neuropathy at the carpal tunnel slowly
      progresses over time, and this can be measured with electrodiagnostics, but
      studies with a much longer interval between electrodiagnostic tests may be needed
      to determine if it always progresses.

PMID- 25386581
TI  - Predictors of missed research appointments in a randomized placebo-controlled
      trial.
AB  - BACKGROUND: The primary aim of this study was to determine predictors of missed
      research appointments in a prospective randomized placebo injection-controlled
      trial with evaluations 1 to 3 and 5 to 8 months after enrollment. METHODS: This
      study represents a secondary use of data from 104 patients that were enrolled in
      a prospective randomized controlled trial of dexamethasone versus lidocaine
      (placebo) injection for various diagnoses. Patients were enrolled between June
      2003 and February 2008. Sixty-three patients (61%) had lateral epicondylosis, 17
      patients (16%) had trapeziometacarpal arthrosis, and 24 patients (23%) had de
      Quervain syndrome. Each patient completed a set of questionnaires at time of
      enrollment. Bivariable and multivariable analyses were used to determine factors
      associated with missed research appointments. RESULTS: Fourteen patients (13%)
      did not return for the first follow-up and 33 patients (32%) did not return for
      the second follow-up. The best multivariable logistic regression model for
      missing the first research visit explained 35% of the variability and included
      younger age, belief that health can be controlled, and no college education. The
      best model for missing the second research visit explained 17% of the variability
      and included greater pain intensity, less personal responsibility for health, and
      diagnosis (trapeziometacarpal arthrosis and de Quervain syndrome). CONCLUSIONS:
      Younger patients with no college education, who believe their health can be
      controlled, are more likely to miss a research appointment when enrolled in a
      randomized placebo injection-controlled trial.

PMID- 25386582
TI  - Current rates of publication for podium and poster presentations at the american
      society for surgery of the hand annual meetings.
AB  - BACKGROUND: Research projects are presented at the Annual Meetings of the
      American Society for Surgery of the Hand (ASSH). It is unknown how many achieve
      publication in peer-reviewed journals. We sought to determine current rates of
      publication of podium and poster presentations. METHODS: All ASSH podium and
      poster presentations from 2000 to 2005 were reviewed, and an Internet-based
      search using PubMed and Google was conducted to determine whether the presented
      studies had been published. Times to publication and journal names were recorded.
      Data were analyzed with descriptive statistics. Fisher's exact test was conducted
      to compare current trends with previous trends. RESULTS: Of 1127 podium and
      poster presentations reviewed, 46% were published in peer-reviewed journals.
      Forty-seven percent of published presentations (242 presentations) were in
      Journal of Hand Surgery, and 11% (59 presentations) were in Journal of Bone and
      Joint Surgery. Forty-five percent of presentations were published within 2 years
      and 66% within 3 years. The publication rate for podium presentations was
      significantly higher than that previously reported for Journal of Hand Surgery,
      at 54% compared with 44% (P=0.004). CONCLUSIONS: Currently, fewer than half of
      the studies presented at Annual Meetings of the ASSH achieve publication in peer
      reviewed journals. Presentations are most likely to be published within 3 years,
      and almost half are published in Journal of Hand Surgery.

PMID- 25386583
TI  - Anterior ankle arthrodesis with molded plate: technique and outcomes.
AB  - BACKGROUND: There is still controversy regarding the best technique for ankle
      arthrodesis to acheive stable rigid fixation along with reconstructing a
      functional plantigrade foot. Moreover, existing techniques have complictions
      related to stability, soft tissue covering, fusion rate, and exposure. METHODS:
      With the anterior approach exactly on the tibialis anterior sheath, the joint was
      exposed and previous hardware, if any, was removed and with the safe direct
      approach, the ankle, hindfoot, and indirectly the subtalar joints were accessed.
      Then fresh cancellous bone was obtained and complete denudation was preformed.
      Lastly, a narrow 4.5 millimeter plate was carefully placed on what was determined
      to be the best final position.In this prospective study, 12 patients with severe
      ankle pain and arthritis enrolled from February 2010 to January 2012. Eight of
      them had posttraumatic arthritis and deformity with hardware, two had rheumatoid
      arthritis, one had poliomyelitis with severe deformity of the foot and knee, and
      another had chronic ulcerative synovitis of the ankle joint. The patients were
      assessed clinically and radiographically for an average of two years (range: 13
      months to 4 years) for functional recovery, range of motion, stability of the
      ankle, and imaging evidence of union. RESULTS: Ankle deformities and pain in all
      12 cases were corrected. With a short healing time and rapid recovery period,
      after six weeks all of the patients could walk independently. Also, scores of the
      Manchester-Oxford Foot Questionnaire (MOXFQ) improved significantly from 69
      preoperatively to 33 postoperatively). CONCLUSIONS: Anterior ankle arthrodesis
      with molded plating can be an easy and safe way to manage deformities and it has
      excellent fusion rate and sufficient rigid fixation.

PMID- 25386584
TI  - The Comparison of Results of Treatment of Midshaft Clavicle Fracture between
      Operative Treatment with Plate and Non-Operative Treatment.
AB  - BACKGROUND: Clavicle fractures are common and usually heal without complications.
      In this study, we evaluated the outcomes of non-operative versus operative
      management of displaced fractures. METHODS: In a prospective clinical trial
      study, sixty-five patients with displaced clavicle mid-shaft fractures were non
      randomly divided in two treatment groups. The first group underwent non-operative
      treatment with figure of 8 bandage (30 patients), and the other underwent
      operative treatment with plate fixation (35 patients). Figure of 8 bandage and
      3.5 millimeter DCP plate with at least six cortical screws were used in non
      operative and operative groups respectively. We followed up all patients at weeks
      2, 6 and 12, and at month sixth. In addition to clinical examination and x-ray
      evaluation, we assessed satisfaction, DASH and Constant Shoulder Score for each
      individual. RESULTS: The average durations of union were 19.3 and 24.4 weeks in
      operative and non-operative groups respectively (P=0.006). Satisfaction with
      operative treatment was 74.3% and with non-operative treatment was 66.7%, showing
      no significant difference (P=0.500). The non-union rate was 5.7% in the operative
      group and 13.3% in the non-operative group (P=0.518). A significant difference
      between the two groups in terms of DASH and Constant Shoulder Scores after the
      six-month follow-up was not found (P=0.352). CONCLUSIONS: According to our
      results, we recommend operative treatment in mid-shaft clavicle fractures only
      when there is a definitive indication.

PMID- 25386585
TI  - A Comparison of Glenohumeral Internal and External Range of Motion and Rotation
      Strength in healthy and Individuals with Recurrent Anterior Instability.
AB  - BACKGROUND: The glenohumeral joint becomes dislocated more than any other major
      joint because it maintains a wide range of motion and its stability is inherently
      weak. The most common complication following acute initial shoulder dislocation
      is recurrent dislocation or chronic instability. Imbalance of strength and range
      of motion in individuals with anterior dislocation can be a contributing factor
      in recurrent dislocation as well. METHODS: This case-control study consisted of
      24 individuals with a mean age of 24.29+/-4.33 years, and a mean dislocation rate
      of 5.37+/-3.62 times. Isometric cuff strength was measured using a handheld
      dynamometer and for range of motion, the Leighton flexometer was used in internal
      and external rotational motions of both upper extremities. Independent t-test was
      used for data analysis. RESULTS: The internal and external range of motion of the
      injured glenohumeral joint was lower than the uninjured joint (P<0.001).
      Similarly, the internal and external rotation strength of the injured joint was
      lower than the uninjured joint (P<0.001). CONCLUSIONS: According to previous
      data, imbalance of strength and range of motion in individuals with anterior
      shoulder dislocation can be a contributing factor in long-term disability and
      increased recurrent dislocation and our finding confirm decreased range of motion
      and strength in our patients. Hence, proper exercise and rehabilitation plans
      need to be developed for those suffering from this complication.

PMID- 25386586
TI  - Clinical outcomes after arthroscopic release for recalcitrant frozen shoulder.
AB  - BACKGROUND: To explain the role of arthroscopic release in intractable frozen
      shoulders. We used different questionnaires and measuring tools to understand
      whether arthroscopic release is the superior modality to treat patients with
      intractable frozen shoulders. METHODS: Between 2007 and 2013, in a prospective
      study, we enrolled 80 patients (52 females and 28 males) with recalcitrant frozen
      shoulder, who underwent arthroscopic release at Ghaem Hospital, a tertiary
      referral center, in Mashhad, Iran. Before operation, all patients filled out the
      Disability of Arm, Shoulder and Hand (DASH), Constant, University of California
      Los Angeles (UCLA), ROWE and Visual Analogue Scale (VAS) for pain questionnaires.
      We measured the difference in range of motion between both the normal and the
      frozen shoulders in each patient. RESULTS: The average age of the patients was
      50.8+/-7.1 years. In 49 patients, the right shoulder was affected and in the
      remaining 31 the left side was affected. Before surgery, the patients were
      suffering from this disease on average for 11.7+/-10.3 months. The average time
      to follow-up was 47.2+/-6.8 months (14 to 60 months). Diabetes mellitus (38%) and
      history of shoulder trauma (23%) were the most common comorbidities in our
      patients. We did not find any significant differences between baseline
      characteristics of diabetics patients with non-diabetics ones. After surgery, the
      average time to achieve maximum pain improvement and range of motion were 3.6+/
      2.1 and 3.6+/-2 months, respectively. The VAS score, constant shoulder score,
      Rowe score, UCLA shoulder score, and DASH score showed significant improvement in
      shoulder function after surgery, and shoulder range of motion improved in all
      directions compared to pre-operation range of motion. CONCLUSIONS: According to
      our results, arthroscopic release of recalcitrant frozen shoulder is a valuable
      modality in treating this disease. This method could decrease pain and improve
      both subjective and objective mid-term outcomes.

PMID- 25386587
TI  - Epidemiology of hand injuries in children presenting to an orthopedic trauma
      center in southeast of iran.
AB  - BACKGROUND: Hand injuries are among the most common childhood injuries. No study
      has been performed regarding the epidemiology of hand injuries in the pediatric
      population of Iran. This study aimed to examine the epidemiology of hand injuries
      among children in southeast of Iran. METHODS: This cross-sectional study was
      performed via census sampling on patients, aged 16 years or less, with a final
      diagnosis of hand injury. Patients presenting to the orthopedic department of
      Khatam-al-Anbia General Hospitalof Zahedan, Iran, were selected from March 2012
      to December 2013. Data were analyzed retrospectively, using a chart review.
      RESULTS: Two-hundred patients (136 males and 64 females with the mean age of 13+/
      2.8 years) with 205 hand injuries were included in this study. As the results
      indicated, door-related injuries were the most common type (25%), accounting for
      24% and 28% of injuries in male and female patients, respectively (P=0.016). Most
      injuries occurred at home (64%) and the lowest number was reported at school(22%)
      (P=0.012). Compared to boys, girls were more likely to be injured at home (78%
      vs. 57%) (P=0.13). In addition, the dominant hand was mostly injured by doors
      (28%). The most common type of injury was laceration(81%) and the least common
      type was finger amputation (7%); also, children with finger amputation were
      significantly younger than those with other types of hand injuries (P<0.001).
      Thumb alone (20%) and index and middle fingers together with anequal percentage
      (3.5%) were the most commonly injured digits. Also, the mean hospitalization cost
      was 297+/- 38 dollars. CONCLUSIONS: Most hand injuries occurred at home and were
      door-related; they were also more frequentamong younger children. Prospective
      studies in order to identify specific protective door devices could potentially
      decrease the frequency of these injures.

PMID- 25386588
TI  - Intra-articular Ganglion Cyst of the Long Head of the Biceps Tendon Originating
      from the Intertubercular Groove.
AB  - Ganglion cysts commonly occur around the shoulder, mostly in the spinoglenoid and
      suprascapular notches. We report a very rare case of intra articular Ganglion
      cyst of the long head of the biceps tendon that originated from the bicipital
      groove as a rare cause of shoulder pain. 

PMID- 25386589
TI  - Osteoid osteoma in the neck of the Scapula; A misleading case.
AB  - Osteoid osteoma is a benign bone tumor that when located on the base of the
      coracoids process of the scapula is very rare and diagnosis and treatment is
      often delayed because of its rarity. Almost any bone can be involved, but half of
      cases involve the femur or tibia. The radiologic features of osteoid osteoma are
      well known, but these tumors may present with unusual features and be easily
      misdiagnosed. In this report, we present a case of osteoid osteoma of the neck of
      the left scapula that took almost 27 months to be diagnosed accurately. 

PMID- 25386590
TI  - Bilateral intraosseous tumor of the calcaneus with imaging-pathologic discordance
      a case report and literatures review.
AB  - A case of bilateral intraosseous tumor of the calcaneus with different MRI
      imaging is presented. On the left, radiological findings suggest intraosseous
      lipoma, but on the right-sided lesion, imaging studies were not convincing. The
      microscopic report showed foreign body granulomatous reaction, a rare clinical
      pathological discordant. 

PMID- 25386591
TI  - Multiple rib exostoses in a boy: a rare case resulting in surgery secondary to
      cosmetic concerns.
AB  - A seven year-old boy with several painless masses on the ribs and shoulder was
      referred to our hospital. The masses were so prominent that they prevented the
      child's sleep. Since the patient had been ridiculed by his friends due to the rib
      prominences, he had refused to attend school. After clinical and radiological
      evaluations, the masses were diagnosed as hereditary multiple exostoses of the
      shoulder and ribs. He underwent surgery for cosmetic reasons resulting in the
      patient's return to a normal life. 

PMID- 25386592
TI  - Synthesis and antioxidant evaluation of enantiomerically pure bis-(1,2,3
      triazolylmethyl)amino esters from modified alpha-amino acids.
AB  - The efforts for synthesis of enantiomerically pure bis-(1,2,3
      triazolylmethyl)amino esters 6 are reported in good yields from an in situ
      generated alpha-azidomethyl ketone. Optimum experimental conditions were
      established for preparation of alpha-halomethyl ketones 10 and alpha-N,N
      dipropargylamino esters 11, all derived from alpha-amino acids. The starting
      materials reacted under conventional click chemistry conditions, revealing a
      specific reactivity of bromomethyl ketones over chloromethyl ketones. The
      antioxidant activity of compounds 6 was assayed by DPPH method. The compound 6c
      with an IC50 of 75.57 +/- 1.74 MUg mL(-1) was the most active. Technically, this
      methodology allows the preparation of a combinatorial library of analogues with
      different structural characteristics depending on the nature of the modified
      alpha-amino acids employed in the synthesis.

PMID- 25386593
TI  - Corelation between machines assisted endodontic irrigant agitation and apical
      extrusion of debris and irrigant: a laboratory study.
AB  - AIMS: To compare amount of root canal debris and irrigant extruded apically after
      irrigants agitation using closed and open chambers. METHODS AND MATERIAL: Sixty
      maxillary central incisors were selected, decoronated, and mounted in preweighed
      glass vials filled with distilled water. Biomechanical preparation was completed
      using ProTaper rotary files until number F4 and 1 mL of 3% NaOCl solution after
      each file use. Samples were randomly divided into closed or open chamber sets
      which were further subdivided into 6 groups, based on the agitation techniques:
      no agitation (control), canalBrush, lentulospiral, passive ultrasonic agitation
      (PUA), EndoActivator, and EndoVac. Canals were irrigated with 1 mL of 17% EDTA
      and agitated for 30 s and then flushed with 2 mL of distilled water. Apically
      extruded irrigant was measured and vials were kept in incubator for 5 days at 68 
      degrees C for drying for weight calculation. Statistical Analysis. Analysis was
      done using Student's t-test, one-way ANOVA, and post-hoc. RESULTS: All agitation
      techniques showed apical extrusion of the debris and irrigant. The closed chamber
      apparatus showed significantly less extrusion of debris and irrigant than open
      chamber (P < 0.05). CONCLUSIONS: EndoVac was found to be the safest agitation
      system among all test groups with regard to apical extrusion of debris and
      irrigant.

PMID- 25386594
TI  - Biosorption of microelements by Spirulina: towards technology of mineral feed
      supplements.
AB  - Surface characterization and metal ion adsorption properties of Spirulina sp. and
      Spirulina maxima were verified by various instrumental techniques. FTIR
      spectroscopy and potentiometric titration were used for qualitative and
      quantitative determination of metal ion-binding groups. Comparative FTIR spectra
      of natural and Cu(II)-treated biomass proved involvement of both phosphoryl and
      sulfone groups in metal ions sorption. The potentiometric titration data analysis
      provided the best fit with the model assuming the presence of three types of
      surface functional groups and the carboxyl group as the major binding site. The
      mechanism of metal ions biosorption was investigated by comparing the results
      from multielemental analyses by ICP-OES and SEM-EDX. Biosorption of Cu(II),
      Mn(II), Zn(II), and Co(II) ions by lyophilized Spirulina sp. was performed to
      determine the metal affinity relationships for single- and multicomponent
      systems. Obtained results showed the replacement of naturally bound ions: Na(I),
      K(I), or Ca(II) with sorbed metal ions in a descending order of Mn(II) > Cu(II) >
      Zn(II) > Co(II) for single- and Cu(II) > Mn(II) > Co(II) > Zn(II) for
      multicomponent systems, respectively. Surface elemental composition of natural
      and metal-loaded material was determined both by ICP-OES and SEM-EDX analysis,
      showing relatively high value of correlation coefficient between the
      concentration of Na(I) ions in algal biomass.

PMID- 25386595
TI  - Retrospective review on the use of topical cyclosporin a 0.05% for paediatric
      allergic conjunctivitis in Hong Kong Chinese.
AB  - PURPOSE: To evaluate the efficacy of using topical cyclosporin A 0.05% (Restasis)
      for the treatment of paediatric allergic conjunctivitis. METHODS: This
      retrospective study included consecutive cases of paediatric allergic
      conjunctivitis treated with Restasis between 2010 and 2013. Subjects with follow
      up time less than 3 months after using Restasis were excluded. Itch severity
      score, symptom score, and sign score were compared before (baseline) and 3 months
      after using Restasis. RESULTS: In 27 eyes of 14 patients (mean age 10.8 +/- 3.2
      years), 44.4% had allergic conjunctivitis, 33.3% had vernal keratoconjunctivitis,
      and 22.2% had atopic keratoconjunctivitis. The mean duration of ocular symptoms
      was 20.4 +/- 13.2 months. 92.6% of subjects were using steroid eye drop before
      Restasis. After 3 months of topical Restasis, there were statistically
      significant reductions in the symptom, sign, and itch severity scores compared
      with baseline (all P <= 0.001) and 78.6% of subjects were able to be tapered off
      steroid eye drops. CONCLUSION: Topical Restasis was effective and safe in
      significantly reducing ocular itchiness, sign, and symptom scores at 3 months
      after use in paediatric allergic ocular conditions.

PMID- 25386596
TI  - Mesoscale model to select the ideal location for new vineyard plantations in the
      Rioja qualified denomination of origin.
AB  - La Rioja is the region where the top rated wines from Spain come from and also
      the origin of one of the most prestigious wines in the world. It is worldwide
      recognized, not only for the quality of the vine, but also for the many factors
      involved in the process that are controllable by the farmer, such as fertilizers,
      irrigation, etc. Likewise, there are other key factors, which cannot be
      controlled that play, however, a crucial role in the quality of the wine, such as
      temperature, radiation, humidity, and rainfall. This research is focused on two
      of these factors: temperature and irradiation. The objective of this paper is to
      be able to recognize these factors, so as to ensure a proper decision criterion
      when selecting the best location for new vineyard plantations. To achieve this
      objective, a mesoscale model MM5 is used, and its performance is assessed and
      compared using different parameters, from the grid resolution to the physical
      parameterization of the model. Finally, the study evaluates the impact of the
      different parameterizations and options for the simulation of meteorological
      variables particularly relevant when choosing new vineyard sites (rainfall
      frequency, temperature, and sun exposure). 

PMID- 25386597
TI  - A comparison of intralesional triamcinolone acetonide injection for primary
      chalazion in children and adults.
AB  - PURPOSE: To investigate outcome differences of intralesional triamcinolone
      acetonide (TA) injection for primary chalazia in children versus adults. METHODS:
      A retrospective review of consecutive subjects with primary chalazion who
      received intralesional TA injection was conducted. A single investigator injected
      0.05-0.15 mL of TA (40 mg/mL) intralesionally. Patients were stratified into the
      pediatric (<18 years old) and adult (>= 18 years old) group. In both groups, the
      correlation of resolution time with chalazion size and TA dose was performed.
      RESULTS: 17 children and 24 adults were enrolled, with a mean age of 7.4 +/- 5.5
      and 39.3 +/- 16.7 years, respectively. Both groups had statistically similar
      baseline characteristics. There was no significant difference between the
      resolution time in the pediatric (18.2 +/- 11.4 days) and adult (16.5 +/- 11.0
      days) group (P = 0.7). There were no significant complications from the TA
      injection. There was no significant correlation of resolution time to chalazion
      size (P = 0.7) nor TA dose (P = 0.3) in both groups. CONCLUSION: TA for the
      treatment of primary chalazion was equally effective in children and adults,
      without any significant complications, and the rate of clinical response did not
      appear to be dose-dependent.

PMID- 25386598
TI  - Drought analysis for Kuwait using standardized precipitation index.
AB  - Implementation of adequate measures to assess and monitor droughts is recognized
      as a major matter challenging researchers involved in water resources management.
      The objective of this study is to assess the hydrologic drought characteristics
      from the historical rainfall records of Kuwait with arid environment by employing
      the criterion of Standardized Precipitation Index (SPI). A wide range of monthly
      total precipitation data from January 1967 to December 2009 is used for the
      assessment. The computation of the SPI series is performed for intermediate- and
      long-time scales of 3, 6, 12, and 24 months. The drought severity and duration
      are also estimated. The bivariate probability distribution for these two drought
      characteristics is constructed by using Clayton copula. It has been shown that
      the drought SPI series for the time scales examined have no systematic trend
      component but a seasonal pattern related to rainfall data. The results are used
      to perform univariate and bivariate frequency analyses for the drought events.
      The study will help evaluating the risk of future droughts in the region,
      assessing their consequences on economy, environment, and society, and adopting
      measures for mitigating the effect of droughts. 

PMID- 25386599
TI  - New formulae for the high-order derivatives of some Jacobi polynomials: an
      application to some high-order boundary value problems.
AB  - This paper is concerned with deriving some new formulae expressing explicitly the
      high-order derivatives of Jacobi polynomials whose parameters difference is one
      or two of any degree and of any order in terms of their corresponding Jacobi
      polynomials. The derivatives formulae for Chebyshev polynomials of third and
      fourth kinds of any degree and of any order in terms of their corresponding
      Chebyshev polynomials are deduced as special cases. Some new reduction formulae
      for summing some terminating hypergeometric functions of unit argument are also
      deduced. As an application, and with the aid of the new introduced derivatives
      formulae, an algorithm for solving special sixth-order boundary value problems
      are implemented with the aid of applying Galerkin method. A numerical example is
      presented hoping to ascertain the validity and the applicability of the proposed
      algorithms. 

PMID- 25386600
TI  - Examining the relationship between cardiorespiratory fitness and body weight
      status: empirical evidence from a population-based survey of adults in Taiwan.
AB  - BACKGROUND: Cardiovascular disease is the number one cause of death worldwide.
      Meanwhile, obesity has been recognized as a global epidemic. This study aims to
      examine the extent to which cardiorespiratory fitness is associated with body
      mass among adult males and females in Taiwan. MaTERIALS AND METHODS: A nationally
      representative dataset consisting of 68,175 adults aged 18-60, including 31,743
      males and 36,432 females, was used. Several multivariate regression models were
      used to investigate the relationship between cardiorespiratory fitness and body
      weight status, after controlling for adults' sociodemographic status. RESULTS: A
      one-unit increase in the BMI lowered the cardiorespiratory fitness score by 0.316
      and 0.368 points for adult males and females, respectively. Among adult males,
      compared to those of normal weight, adult males who were underweight, overweight,
      or obese had a lower cardiorespiratory fitness score by 1.287, 0.845, and 3.353
      points, respectively. Similar results could be found in female samples.
      CONCLUSION: The overweight and obese adults had much lower levels of
      cardiorespiratory fitness as compared to their normal weight counterparts. Given
      the upward trend in the prevalence of overweight and obesity, it is important to
      help overweight and obese people to become more fit and reach their healthy
      weight.

PMID- 25386601
TI  - Fascia wrapping technique: a modified method for the treatment of cubital tunnel
      syndrome.
AB  - Variations of the anterior transposition of the ulnar nerve for cubital tunnel
      syndrome include subcutaneous, submuscular, intramuscular, and subfascial
      methods. We introduce a modification of subfascial transposition, which is
      designed to facilitate nerve gliding by wrapping the nerve with fascia. Twenty
      patients with wrapping surgery following the diagnosis of cubital tunnel syndrome
      were reviewed retrospectively. Preoperative electrodiagnostic studies were
      performed in all patients and all of them were rechecked postoperatively. The
      preoperative mean value of motor conduction velocity (MCV) was 37.1 +/- 6.7 m/s
      within the elbow segment and this result showed a decrease compared to the result
      of MCV with 53.9 +/- 6.9 m/s in the below the elbow-wrist segment with
      statistical significance (P < 0.05). Postoperative mean values of MCV were
      improved in all of 20 patients to 47.6 +/- 5.5 m/s (P < 0.05). 19 patients of 20
      (95%) reported good or excellent clinical outcomes according to a modified Bishop
      scoring system. The surgical treatment methods for cubital tunnel syndrome have
      their own advantages and disadvantages, and the preferred method differs
      depending on the surgeon. The wrapping method of anterior transposition is a
      newly designed alternative method modified from subfascial transposition. This
      method could be an alternative option to treat cubital tunnel syndrome.

PMID- 25386602
TI  - Germination and early growth of Brassica juncea in copper mine tailings amended
      with technosol and compost.
AB  - Mine tailings represent a serious threat to the environment and human health;
      thus their restoration has become a major concern. In this study, the
      interactions between Brassica juncea and different mine soil treatments were
      evaluated in order to understand their effect on germination and early growth.
      Three soil treatments containing 25% and 50% of technosol and 30% of compost were
      prepared. Germination and early growth were assessed in soil and pore water
      extracts from the treatments. Unlike the untreated mine soil, the three
      treatments allowed germination and growth, achieving levels comparable to those
      of seedlings from the same species developed in normal conditions. The seedlings
      grown in 50% of technosol and 30% of compost exhibited greater germination
      percentages, higher growth, and more efficient mechanisms against oxidative
      stress, ascribed to the organic matter and nutrients content of these treatments.
      Considering the unequivocal ability of B. juncea for phytoremediation, the
      results suggest that technosol and compost may be an auspicious solution to allow
      the germination and early growth of this species in mine tailings. 

PMID- 25386603
TI  - Effect of CPP/ACP on initial bioadhesion to enamel and dentin in situ.
AB  - The present in situ study investigated the influence of a preparation containing
      CPP/ACP (caseinphosphopeptide-amorphous calcium phosphate) (GC Tooth mousse) on
      initial bacterial colonization of enamel and dentin. Therefore, pellicle
      formation was performed in situ on bovine enamel and dentin specimens fixed to
      individual upper jaw splints worn by 8 subjects. After 1 min of pellicle
      formation GC Tooth mousse was used according to manufacturer's recommendations.
      Rinses with chlorhexidine served as positive controls. Specimens carried without
      any rinse served as negative controls. After 8 h overnight exposure of the
      splints, bacterial colonization was quantified by fluorescence microscopy (DAPI
      and BacLight live/dead staining). Additionally, the colony forming units (CFU)
      were determined after desorption. Furthermore, the effects on Streptococcus
      mutans bacteria were tested in vitro (BacLight). There was no significant impact
      of CPP/ACP on initial bacterial colonization proved with DAPI and BacLight.
      Determination of CFU showed statistical significance for CPP/ACP to reduce
      bacterial adherence on enamel. The in vitro investigation indicated no
      antimicrobial effects for CPP/ACP on Streptococcus mutans suspension. Under the
      chosen conditions, CPP/ACP (GC Tooth mousse) had no significant impact on initial
      biofilm formation on dental hard tissues. The tested preparation cannot be
      recommended for biofilm management.

PMID- 25386604
TI  - Disparity map generation from illumination variant stereo images using efficient
      hierarchical dynamic programming.
AB  - A novel hierarchical stereo matching algorithm is presented which gives disparity
      map as output from illumination variant stereo pair. Illumination difference
      between two stereo images can lead to undesirable output. Stereo image pair often
      experience illumination variations due to many factors like real and practical
      situation, spatially and temporally separated camera positions, environmental
      illumination fluctuation, and the change in the strength or position of the light
      sources. Window matching and dynamic programming techniques are employed for
      disparity map estimation. Good quality disparity map is obtained with the
      optimized path. Homomorphic filtering is used as a preprocessing step to lessen
      illumination variation between the stereo images. Anisotropic diffusion is used
      to refine disparity map to give high quality disparity map as a final output. The
      robust performance of the proposed approach is suitable for real life
      circumstances where there will be always illumination variation between the
      images. The matching is carried out in a sequence of images representing the same
      scene, however in different resolutions. The hierarchical approach adopted
      decreases the computation time of the stereo matching problem. This algorithm can
      be helpful in applications like robot navigation, extraction of information from
      aerial surveys, 3D scene reconstruction, and military and security applications.
      Similarity measure SAD is often sensitive to illumination variation. It produces
      unacceptable disparity map results for illumination variant left and right
      images. Experimental results show that our proposed algorithm produces quality
      disparity maps for both wide range of illumination variant and invariant stereo
      image pair. 

PMID- 25386605
TI  - Proactive supply chain performance management with predictive analytics.
AB  - Today's business climate requires supply chains to be proactive rather than
      reactive, which demands a new approach that incorporates data mining predictive
      analytics. This paper introduces a predictive supply chain performance management
      model which combines process modelling, performance measurement, data mining
      models, and web portal technologies into a unique model. It presents the supply
      chain modelling approach based on the specialized metamodel which allows
      modelling of any supply chain configuration and at different level of details.
      The paper also presents the supply chain semantic business intelligence (BI)
      model which encapsulates data sources and business rules and includes the data
      warehouse model with specific supply chain dimensions, measures, and KPIs (key
      performance indicators). Next, the paper describes two generic approaches for
      designing the KPI predictive data mining models based on the BI semantic model.
      KPI predictive models were trained and tested with a real-world data set.
      Finally, a specialized analytical web portal which offers collaborative
      performance monitoring and decision making is presented. The results show that
      these models give very accurate KPI projections and provide valuable insights
      into newly emerging trends, opportunities, and problems. This should lead to more
      intelligent, predictive, and responsive supply chains capable of adapting to
      future business environment. 

PMID- 25386606
TI  - A study of correlations within the dimensions of lower limb parts for personal
      identification in a Sudanese population.
AB  - The presence of an isolated limb or limb parts from different individuals
      presents a major challenge for medicolegal investigators in establishing
      identification in cases of wars, mass disasters, and criminal assaults because
      different populations have different sizes and proportions. The measurement of
      lower limb dimensions showed a high success rate in establishing individual
      identity in terms of sex and stature in various populations. However, there is a
      paucity of data concerning the correlation within the lower limb parts. This
      study aims to assess the existence of relationships within lower limb parts and
      to develop regression formulae to reconstruct limb parts from one another. The
      tibial length, bimalleolar breadth, foot length, and foot breadth of 376 right
      handed Sudanese adults were measured. The results showed that all variables were
      significantly larger in males than in females. A significant positive correlation
      (P < 0.001) was found within the lower limb parts. Sex-specific linear equations
      and multiple regression equations were developed to reconstruct the lower limb
      parts in the presence of single dimension or multiple dimensions from the same
      limb. The use of multiple regression equations provided a better reconstruction
      than simple regression equations. These results are significant in forensics and
      orthopedic reconstructive surgery. 

PMID- 25386607
TI  - A secure operational model for mobile payments.
AB  - Instead of paying by cash, check, or credit cards, customers can now also use
      their mobile devices to pay for a wide range of services and both digital and
      physical goods. However, customers' security concerns are a major barrier to the
      broad adoption and use of mobile payments. In this paper we present the design of
      a secure operational model for mobile payments in which access control is based
      on a service-oriented architecture. A customer uses his/her mobile device to get
      authorization from a remote server and generate a two-dimensional barcode as the
      payment certificate. This payment certificate has a time limit and can be used
      once only. The system also provides the ability to remotely lock and disable the
      mobile payment service. 

PMID- 25386608
TI  - East China Sea Storm Surge Modeling and Visualization System: the Typhoon Soulik
      case.
AB  - East China Sea (ECS) Storm Surge Modeling System (ESSMS) is developed based on
      Regional Ocean Modeling System (ROMS). Case simulation is performed on the
      Typhoon Soulik, which landed on the coastal region of Fujian Province, China, at
      6 pm of July 13, 2013. Modeling results show that the maximum tide level happened
      at 6 pm, which was also the landing time of Soulik. This accordance may lead to
      significant storm surge and water level rise in the coastal region. The water
      level variation induced by high winds of Soulik ranges from -0.1 to 0.15 m. Water
      level generally increases near the landing place, in particular on the left hand
      side of the typhoon track. It is calculated that 0.15 m water level rise in this
      region can cause a submerge increase of ~0.2 km(2), which could be catastrophic
      to the coastal environment and the living. Additionally, a Globe Visualization
      System (GVS) is realized on the basis of World Wind to better provide users with
      the typhoon/storm surge information. The main functions of GVS include data
      indexing, browsing, analyzing, and visualization. GVS is capable of facilitating
      the precaution and mitigation of typhoon/storm surge in ESC in combination with
      ESSMS.

PMID- 25386609
TI  - A clinical trial to investigate the effect of Cynatine HNS on hair and nail
      parameters.
AB  - OBJECTIVE: A new, novel product, Cynatine HNS, was evaluated for its effects as a
      supplement for improving various aspects of hair and nails in a randomized,
      double-blind, placebo-controlled clinical trial. METHODS: A total of 50 females
      were included and randomized into two groups. The active group (n = 25) received
      2 capsules containing Cynatine HNS, comprised of Cynatine brand keratin (500 mg)
      plus vitamins and minerals, per day, and the placebo group (n = 25) received 2
      identical capsules of maltodextrin per day for 90 days. End points for hair loss,
      hair growth, hair strength, amino acid composition, and hair luster were
      measured. End points were also measured for nail strength and the appearance of
      nails. RESULTS: The results show that subjects taking Cynatine HNS showed
      statistically significant improvements in their hair and nails when compared to
      placebo. CONCLUSION: Cynatine HNS is an effective supplement for improving hair
      and nails in 90 days or less. EudraCT number is 2014-002645-22.

PMID- 25386610
TI  - Cerebral arteriovenous malformations: evaluation and management.
AB  - There has been increased detection of incidental AVMs as result of the frequent
      use of advanced imaging techniques. The natural history of AVM is poorly
      understood and its management is controversial. This review provides an overview
      of the epidemiology, pathophysiology, natural history, clinical presentation,
      diagnosis, and management of AVMs. The authors discussed the imaging techniques
      available for detecting AVMs with regard to the advantages and disadvantages of
      each imaging modality. Furthermore, this review paper discusses the factors that
      must be considered for the most appropriate management strategy (based on the
      current evidence in the literature) and the risks and benefits of each management
      option. 

PMID- 25386611
TI  - Spatial and temporal variability of polycyclic aromatic hydrocarbons in sediments
      from yellow river-dominated margin.
AB  - Polycyclic aromatic hydrocarbons (PAHs) were analyzed for surface sediments and a
      sediment core from the Yellow River-dominated margin. The concentration of 16
      USEPA priority PAHs in surface sediments ranged from 5.6 to 175.4 ng g(-1) dry
      weight sediment (dws) with a mean of 49.1 ng g(-1) dws. From 1930 to 2011, the
      distribution of PAHs (37.2 to 210.6 ng g(-1) dws) was consistent with the
      socioeconomic development of China. The PAHs' concentration peaked in 1964 and
      1986, corresponding to the rapid economic growth in China (1958-1965) and the
      initiation of the "Reform and Open" policy in 1978, respectively. The
      applications of molecular diagnostic ratios and principal component analysis
      suggest that PAHs are predominantly produced by the coal and biomass combustion,
      whereas the contribution of petroleum combustions slightly increased after the
      1970s, synchronous with an increasing usage of oil and gas in China.

PMID- 25386612
TI  - Storage-efficient 16-Bit Hybrid IP traceback with Single Packet.
AB  - Since adversaries may spoof their source IPs in the attacks, traceback schemes
      have been proposed to identify the attack source. However, some of these schemes'
      storage requirements increase with packet numbers. Some even have false positives
      because they use an IP header's fragment offset for marking. Thus, we propose a
      16-bit single packet hybrid IP traceback scheme that combines packet marking and
      packet logging with high accuracy and low storage requirement. The size of our
      log tables can be bounded by route numbers. We also set a threshold to determine
      whether an upstream interface number is stored in a log table or in a marking
      field, so as to balance the logging frequency and our computational loads.
      Because we store user interface information on small-degree routers, compared
      with current single packet traceback schemes, ours can have the lowest storage
      requirements. Besides, our traceback achieves zero false positive/negative rates
      and guarantees reassembly of fragmented packets at the destination. 

PMID- 25386613
TI  - A novel N-input voting algorithm for X-by-wire fault-tolerant systems.
AB  - Voting is an important operation in multichannel computation paradigm and
      realization of ultrareliable and real-time control systems that arbitrates among
      the results of N redundant variants. These systems include N-modular redundant
      (NMR) hardware systems and diversely designed software systems based on N-version
      programming (NVP). Depending on the characteristics of the application and the
      type of selected voter, the voting algorithms can be implemented for either
      hardware or software systems. In this paper, a novel voting algorithm is
      introduced for real-time fault-tolerant control systems, appropriate for
      applications in which N is large. Then, its behavior has been software
      implemented in different scenarios of error-injection on the system inputs. The
      results of analyzed evaluations through plots and statistical computations have
      demonstrated that this novel algorithm does not have the limitations of some
      popular voting algorithms such as median and weighted; moreover, it is able to
      significantly increase the reliability and availability of the system in the best
      case to 2489.7% and 626.74%, respectively, and in the worst case to 3.84% and
      1.55%, respectively. 

PMID- 25386614
TI  - Closed-form equation of data dependent jitter in first order low pass system.
AB  - This paper presents a closed-form equation of data dependent jitter (DDJ) in
      first order low pass systems. The DDJ relates to the system bandwidth, the bit
      rate, the input rise/fall time, and the number of maximum consecutive identical
      bits of the data pattern. To confirm the derived equation, simulations have been
      done with a first order RC low pass circuit for various system bandwidths, bit
      rates, input rise/fall times, and data patterns. The simulation results agree
      well with the calculated DDJ values by the derived equation. 

PMID- 25386615
TI  - Dental fear among medical and dental undergraduates.
AB  - OBJECTIVE: To assess the prevalence and level of dental fear among health related
      undergraduates and to identify factors causing such fear using Kleinknecht's
      Dental Fear Survey (DFS) questionnaire. METHODS: Kleinknecht's DFS questionnaire
      was used to assess dental fear and anxiety among the entire enrollment of the
      medical and dental undergraduates' of the University of Malaya. RESULTS: Overall
      response rate was 82.2%. Dental students reported higher prevalence of dental
      fear (96.0% versus 90.4%). However, most of the fear encountered among dental
      students was in the low fear category as compared to their medical counterpart
      (69.2 versus 51.2%). Significantly more medical students cancelled dental
      appointment due to fear compared to dental students (P = 0.004). "Heart beats
      faster" and "muscle being tensed" were the top two physiological responses
      experienced by the respondents. "Drill" and "anesthetic needle" were the most
      fear provoking objects among respondents of both faculties. CONCLUSION: Dental
      fear and anxiety are a common problem encountered among medical and dental
      undergraduates who represent future health care professionals. Also, high level
      of dental fear and anxiety leads to the avoidance of the dental services.

PMID- 25386616
TI  - The effects of CO2 laser with or without nanohydroxyapatite paste in the
      occlusion of dentinal tubules.
AB  - The aim of this study was to evaluate a new treatment modality for the occlusion
      of dentinal tubules (DTs) via the combination of 10.6 um carbon dioxide (CO2)
      laser and nanoparticle hydroxyapatite paste (n-HAp). Forty-six sound human molars
      were used in the current experiment. Ten of the molars were used to assess the
      temperature elevation during lasing. Thirty were evaluated for dentinal
      permeability test, subdivided into 3 groups: the control group (C), laser only (L
      ), and laser plus n-HAp (L+). Six samples, two per group, were used for surface
      and cross section morphology, evaluated through scanning electron microscope
      (SEM). The temperature measurement results showed that the maximum temperature
      increase was 3.2  degrees C. Morphologically groups (L-) and (L+) presented
      narrower DTs, and almost a complete occlusion of the dentinal tubules for group
      (L+) was found. The Kruskal-Wallis nonparametric test for permeability test data
      showed statistical differences between the groups (P < 0.05). For intergroup
      comparison all groups were statistically different from each other, with group
      (L+) showing significant less dye penetration than the control group. We
      concluded that CO2 laser in moderate power density combined with n-HAp seems to
      be a good treatment modality for reducing the permeability of dentin.

PMID- 25386617
TI  - Miniaturized bandpass filter using a meandered stepped-impedance resonator with a
      meandered-line stub-load on a GaAs substrate.
AB  - This paper reports a compact bandpass filter with improved skirt selectivity
      using integrated passive device fabrication technology on a GaAs substrate. The
      structure of the filter consists of electromagnetically coupled meandered-line
      symmetric stepped-impedance resonators. The strength of the coupling between the
      resonators is enhanced by using a meandered-line stub-load inside the resonators
      to improve the selectivity and miniaturize the size of the filter. In addition,
      the center frequency of the filter can be flexibly controlled by varying degrees
      of the capacitive coupling between resonator and stub-load. To verify the
      proposed concept, a protocol bandpass filter with center frequency of 6.53 GHz
      was designed, fabricated, and measured, with a return loss and insertion loss of
      39.1 dB and 1.63 dB.

PMID- 25386618
TI  - The epiphytic fern Elaphoglossum luridum (Fee) Christ. (Dryopteridaceae) from
      Central and South America: morphological and physiological responses to water
      stress.
AB  - Elaphoglossum luridum (Fee) Christ. (Dryopteridaceae) is an epiphytic fern of the
      Atlantic Forest (Brazil). Anatomical and physiological studies were conducted to
      understand how this plant responds to water stress. The E. luridum frond is
      coriaceus and succulent, presenting trichomes, relatively thick cuticle, and
      sinuous cell walls in both abaxial and adaxial epidermis. Three treatments were
      analyzed: control, water deficit, and abscisic acid (ABA). Physiological studies
      were conducted through analysis of relative water content (RWC), photosynthetic
      pigments, chlorophyll a fluorescence, and malate content. No changes in RWC were
      observed among treatments; however, significant decreases in chlorophyll a
      content and photosynthetic parameters, including optimal irradiance (I opt) and
      maximum electron transport rate (ETRmax), were determined by rapid light curves
      (RLC). No evidence of crassulacean acid metabolism (CAM) pathway was observed in
      E. luridum in response to either water deficit or exogenous application of ABA.
      On the other hand, malate content decreased in the E. luridum frond after ABA
      treatment, seeming to downregulate malate metabolism at night, possibly through
      tricarboxylic acid (TCA) cycle regulation. 

PMID- 25386619
TI  - Human paraoxonase 1 as a pharmacologic agent: limitations and perspectives.
AB  - Human PON1 (h-PON1) is a multifaceted enzyme and can hydrolyze (and inactivate) a
      wide range of substrates. The enzyme shows anti-inflammatory, antioxidative,
      antiatherogenic, ant-diabetic, antimicrobial, and organophosphate (OP)
      detoxifying properties. However, there are certain limitations regarding large
      scale production and use of h-PON1 as a therapeutic candidate. These include
      difficulties in producing recombinant h-PON1 (rh-PON1) using microbial expression
      system, low hydrolytic activity of wild-type h-PON1 towards certain substrates,
      and low storage stability of the purified enzyme. This review summarizes the work
      done in our laboratory to address these limitations. Our results show that (a)
      optimized polynucleotide sequence encoding rh-PON1 can express the protein in an
      active form in E. coli and can be used to generate variant of the enzyme having
      enhanced hydrolytic activity, (b) in vitro refolding of rh-PON1 enzyme can
      dramatically increase the yield of an active enzyme, (c) common excipients can be
      used to stabilize purified rh-PON1 enzyme when stored under different storage
      conditions, and (d) variants of rh-PON1 enzyme impart significant protection
      against OP-poisoning in human blood (ex vivo) and mouse (in vivo) model of OP
      poisoning. The rh-PON1 variants and their process of production discussed here
      will help to develop h-PON1 as a therapeutic candidate. 

PMID- 25386621
TI  - Rapid detection and differentiation of Clonorchis sinensis and Opisthorchis
      viverrini using real-time PCR and high resolution melting analysis.
AB  - Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne
      pathogens, causing serious public health problem in Asia. The present study
      developed an assay integrating real-time PCR and high resolution melting (HRM)
      analysis for the specific detection and rapid identification of C. sinensis and
      O. viverrini. Primers targeting COX1 gene were highly specific for these liver
      flukes, as evidenced by the negative amplification of closely related trematodes.
      Assays using genomic DNA extracted from the two flukes yielded specific
      amplification and their identity was confirmed by sequencing, having the accuracy
      of 100% in reference to conventional methods. The assay was proved to be highly
      sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1
      metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to
      be differentiated by their HRM profiles. The method can reduce labor of
      microscopic examination and the contamination of agarose electrophoresis.
      Moreover, it can differentiate these two flukes which are difficult to be
      distinguished using other methods. The established method provides an alternative
      tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini. 

PMID- 25386622
TI  - The relations among fuzzy t-filters on residuated lattices.
AB  - We give the simple general principle of studying the relations among fuzzy t
      filters on residuated lattices. Using the general principle, we can easily
      determine the relations among fuzzy t-filters on different logical algebras. 

PMID- 25386620
TI  - Functional stability of plasminogen activator inhibitor-1.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen
      activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type
      plasminogen activator (u-PA), and a major regulator of the fibrinolytic system.
      PAI-1 plays a pivotal role in acute thrombotic events such as deep vein
      thrombosis (DVT) and myocardial infarction (MI). The biological effects of PAI-1
      extend far beyond thrombosis including its critical role in fibrotic disorders,
      atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The
      conversion of PAI-1 from the active to the latent conformation appears to be
      unique among serpins in that it occurs spontaneously at a relatively rapid rate.
      Latency transition is believed to represent a regulatory mechanism, reducing the
      risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus,
      relying solely on plasma concentrations of PAI-1 without assessing its function
      may be misleading in interpreting the role of PAI-1 in many complex diseases.
      Environmental conditions, interaction with other proteins, mutations, and
      glycosylation are the main factors that have a significant impact on the
      stability of the PAI-1 structure. This review provides an overview on the current
      knowledge on PAI-1 especially importance of PAI-1 level and stability and
      highlights the potential use of PAI-1 inhibitors for treating cardiovascular
      disease. 

PMID- 25386623
TI  - The Takeda three colors combination test: a screening test for detection of very
      mild Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia and is
      prevalent worldwide. It is expected that AD, for which aging is a risk factor,
      will increase in the future. Because early detection of AD has become
      increasingly important, promoting demand for screening tests with adequate
      sensitivity. In this study, we examined the usefulness of the Takeda Three Colors
      Combination Test (TTCC) for screening of the very mild AD and amnestic mild
      cognitive impairment (aMCI). METHODS: 154 senior persons participated in the
      research: 55 with very mild AD, 45 with aMCI, and 54 control group. The TTCC,
      which was a colored cards configuration memory task, was examined for sensitivity
      and specificity. RESULTS: The sensitivity of the TTCC was 76% and 47% for the
      very mild AD and aMCI groups, and the specificity was 83%. Conducting TTCC
      (including instruction and evaluation) was accomplished within 2 minutes for all
      subjects. CONCLUSION: The TTCC is useful screening test for early detection of
      AD. Furthermore, administration time is short and requires no special training or
      skills. Thus, we believe the TTCC shows great potential for use as an AD
      screening test by a general practitioner in communities worldwide.

PMID- 25386624
TI  - Multistage spectral relaxation method for solving the hyperchaotic complex
      systems.
AB  - We present a pseudospectral method application for solving the hyperchaotic
      complex systems. The proposed method, called the multistage spectral relaxation
      method (MSRM) is based on a technique of extending Gauss-Seidel type relaxation
      ideas to systems of nonlinear differential equations and using the Chebyshev
      pseudospectral methods to solve the resulting system on a sequence of multiple
      intervals. In this new application, the MSRM is used to solve famous hyperchaotic
      complex systems such as hyperchaotic complex Lorenz system and the complex
      permanent magnet synchronous motor. We compare this approach to the Runge-Kutta
      based ode45 solver to show that the MSRM gives accurate results. 

PMID- 25386626
TI  - The effect of row structure on soil moisture retrieval accuracy from passive
      microwave data.
AB  - Row structure causes the anisotropy of microwave brightness temperature (TB) of
      soil surface, and it also can affect soil moisture retrieval accuracy when its
      influence is ignored in the inversion model. To study the effect of typical row
      structure on the retrieved soil moisture and evaluate if there is a need to
      introduce this effect into the inversion model, two ground-based experiments were
      carried out in 2011. Based on the observed C-band TB, field soil and vegetation
      parameters, row structure rough surface assumption (Q p model and discrete
      model), including the effect of row structure, and flat rough surface assumption
      (Q p model), ignoring the effect of row structure, are used to model microwave TB
      of soil surface. Then, soil moisture can be retrieved, respectively, by
      minimizing the difference of the measured and modeled TB. The results show that
      soil moisture retrieval accuracy based on the row structure rough surface
      assumption is approximately 0.02 cm(3)/cm(3) better than the flat rough surface
      assumption for vegetated soil, as well as 0.015 cm(3)/cm(3) better for bare and
      wet soil. This result indicates that the effect of row structure cannot be
      ignored for accurately retrieving soil moisture of farmland surface when C-band
      is used.

PMID- 25386625
TI  - Dietary conjugated linoleic acid alters oxidative stability and alleviates plasma
      cholesterol content in meat of broiler chickens.
AB  - This study was conducted to investigate the effects of dietary conjugated
      linoleic acid (CLA) on fatty acid composition, lipoprotein content, lipid
      peroxidation, and meat colour of broiler chickens. A total of 180 broiler
      chickens were allocated to 3 dietary treatments (0, 2.5, and 5% Lutrell) and
      given a standard broiler starter diet and finisher diet. Body weight of chickens
      and feed intake were recorded weekly. After slaughter, the breast meat was aged
      at 4  degrees C for 0, 3, and 6 days. The fatty acid composition was measured in
      the breast meat. Body weight (BW) and feed efficiency were decreased by dietary
      CLA level (P < 0.05). Chicken fed with 2.5% Lutrell had the highest feed intake
      compared to the control (CON) group. The total CLA increased significantly (P <
      0.05) in breast meat from birds supplemented with CLA. Propensity for lipid
      peroxidation was significantly higher after 6 days of meat storage (P < 0.05) and
      the redness in chicken breast meat was lower in CLA-fed birds (P < 0.05). It is
      also notable that a 5% Lutrell supplementation decreased the plasma total
      cholesterol (TC), low density protein (LDL), and HDL (high-density
      lipoprotein)/LDL ratio in chickens (P < 0.05).

PMID- 25386627
TI  - Occurrence of socransky red complex in pregnant women with and without
      periodontal disease.
AB  - PURPOSE: To verify the presence of Socransky Red Complex (Porphyromonas
      gingivalis, Treponema denticola and Tannerella forsythia) and P. intermedia using
      polymerase chain reaction (PCR) in periodontally healthy pregnant women and
      pregnant women with periodontal disease, as well as its relation to arterial
      blood pressure and capillary glycaemia. MATERIALS AND METHODS: This case control
      study included 86 pregnant women, including 50 pregnant women with healthy
      periodontium, 27 with gingivitis and 9 with periodontitis. Arterial blood
      pressure and glycaemia were evaluated and recorded. Clinical specimens from the
      gingival crevice or periodontal pockets were gathered with sterile absorbent
      paper cones. DNA extraction was accomplished using the Easy-DNA Kit test and the
      presence of bacteria was detected by PCR with primers and specific probes for
      each microorganism. RESULTS: The arterial pressure of all pregnant women was
      found to be within normal levels and 51% presented with hyperglycaemia, these two
      variables were not associated with periodontal conditions and/or presence of
      microorganisms. Socransky Red Complex was not present in pregnant women with
      healthy periodontium; however, it was present in pregnant women with gingivitis
      (3.7%) and in a higher percentage of pregnant women with periodontitis (33.3%).
      CONCLUSION: Socransky Red Complex was found only in cases of periodontal diseases
      and is not related to blood pressure and/or high levels of blood glucose.

PMID- 25386628
TI  - Experience of Early Childhood Caries May Positively Correlate with Psychomotor
      Development.
AB  - PURPOSE: To examine the as yet unknown relationship between dental caries and the
      child's psychomotor development. MATERIALS AND METHODS: A cross-sectional study
      was designed by screening the kindergartens from urban areas of two cities in
      southern Taiwan. Besides the personal, demographic and dietary information, the
      common measures for caries (dmft) and the amended comprehensive scales (CCDI) for
      psychomotor development were used to assess their relationship(s). A power
      analysis showed that 334 subjects would be required. One-way ANOVA vs multiple
      linear regression analysis were used to compare the differences of variables
      between gender, age and dmft scales, vs the relationship among all variables
      tested, respectively. RESULTS: A total of 433 children completed the study. The
      results demonstrated that there was a positive relationship between higher (i.e.
      dmft>=4 and 5) but not lower or extremely high caries experience and aspects of
      psychomotor development (i.e. personal-social and expressive language) in
      children aged 4 to 6 years. CONCLUSION: The present results are important for
      paediatric dentists, as they suggest a positive correlation between caries
      experience (dmft 3 to 6) and psychomotor development in pre-school children and
      that such a correlation may occur more significantly as an attribute of the most
      affected teeth (incisors and molars) during the critical stage of personal-social
      and expressive language development (speech-communication).

PMID- 25386629
TI  - Awareness of General Dental Practitioners about Oral Screening and Biopsy
      Procedures in Udaipur, India.
AB  - PURPOSE: Oral cancer presents with high mortality rates, and the likelihood of
      survival is remarkably better when detected early. The present study aimed to
      assess the awareness of general dental practitioners (GDPs) about oral screening
      and biopsy procedures in Udaipur, India. MATERIALS AND METHODS: In this cross
      sectional study, 83 GDPs were surveyed using a self-administered structured
      questionnaire consisting of several mandatory and optional questions. The data
      were analysed and frequency distribution was performed. RESULTS: Most of the GDPs
      adequately performed complete oral cavity examinations and were aware of
      suspicious oral lesions, most common sites and risk factors for oral pre
      cancer/cancer, but did not inquire about patients' tobacco/ alcohol consumption
      habits. Half of them referred lesions requiring biopsy to a specialist/higher
      centre rather than performing biopsies themselves, even after recognising the
      importance of biopsy as a diagnostic tool due to concerns of inadequate
      experience and instruments required. Varied results regarding selection of the
      appropriate site for biopsy and preservation of biopsied specimens were noted.
      CONCLUSION: Most of the GDPs were adequately aware of oral screening and biopsy
      procedures but felt reluctant to perform them, which suggests that dental
      education programmes are needed for GDPs in oral pre-cancer/cancer detection as
      well as screening and diagnostic procedures.

PMID- 25386630
TI  - Comparative evaluation of terminalia chebula extract mouthwash and chlorhexidine
      mouthwash on plaque and gingival inflammation - 4-week randomised control trial.
AB  - PURPOSE: The present study was conducted to assess the effectiveness of
      Terminalia chebula on plaque and gingival inflammation and compare it with the
      gold standard chlorhexidine (CHX 0.2%) and distilled water as control (placebo).
      MATERIALS AND METHODS: A double-blind randomised control trial was conducted
      among undergraduate students who volunteered. They were randomly allocated into
      three study groups: 1) Terminalia chebula mouthwash (n = 30); 2) chlorhexidine
      (active control) (n = 30); 3) distilled water (placebo) (n = 30). Assessment was
      carried out according to plaque score and gingival score. Statistical analysis
      was carried out to compare the effect of both mouthwashes. ANOVA and post-hoc LSD
      tests were performed using SPSS version 17 with p <= 0.05 considered
      statistically significant. RESULTS: Our result showed that Terminalia chebula
      mouthrinse is as effective as chlorhexidine in reducing dental plaque and
      gingival inflammation. The results demonstrated a significant reduction of
      gingival bleeding and plaque indices in both groups over a period of 15 and 30
      days as compared to the placebo. CONCLUSION: The results of the present study
      indicate that Terminalia chebula may prove to be an effective mouthwash.
      Terminalia chebula extract mouthrinse can be used as an alternative to
      chlorhexidine mouthrinse as it has similar properties without the side-effects of
      the latter.

PMID- 25386631
TI  - Effect of Nonsurgical Periodontal Therapy on the Glycaemic Control of Nondiabetic
      Periodontitis Patients: A Clinical Biochemical Study.
AB  - PURPOSE: To compare the HbA1c levels in nondiabetic subjects with periodontitis
      and periodontally healthy controls and to evaluate the effect of nonsurgical
      periodontal therapy on the glycaemic control in nondiabetic subjects with
      periodontitis. MATERIALS AND METHODS: A total of 220 nondiabetic subjects between
      35 and 60 years old were selected and divided into two groups: group A (case
      group), comprised of subjects with chronic periodontitis, and group B (control
      group), comprised of subjects with healthy periodontium. Periodontal clinical
      parameters (plaque index, modified sulcular bleeding index, probing depth and
      clinical attachment level) were used to assign the subjects into the respective
      groups. The HbA1c level was estimated for both groups using a commercially
      available kit. Subjects in group A underwent nonsurgical periodontal therapy in
      two to four sessions along with oral hygiene instructions. The periodontal
      parameters and HbA1c levels were again evaluated in the test group three months
      following periodontal therapy. RESULTS: The HbA1c levels were higher in the case
      group (A) than the control group (B). Three months following periodontal therapy
      in group A, there was improvement in periodontal parameters. The HbA1c levels
      decreased significantly from baseline to 3 months. CONCLUSION: The results of
      this study found chronic periodontitis to be associated with a significant
      increase in glycosylated haemoglobin levels in nondiabetic periodontitis
      subjects. Furthermore, with improvement of periodontal status, the glycaemic
      levels return to near normal values.

PMID- 25386632
TI  - Assessment of the Accuracy of Two Dental Screening Methods Used in a School
      Setting.
AB  - PURPOSE: To assess the accuracy of two screening methods used by dentists in the
      Health Insurance Organisation in Alexandria, Egypt aiming at identifying children
      who need referral for treatment. MATERIALS AND METHODS: The study included 45
      dentists who examined 30 children using exclusively visual screening (VS) and
      visual screening with tongue blade (VSTB). A benchmark dentist examined the same
      group of children using mirror and probe (MP). VS and VSTB were compared to MP.
      Sensitivity (Sn), specificity (Sp), positive and negative predictive values (PPV
      and NPV, respectively) were calculated. The effect of dentist's gender, year of
      graduation and having postgraduate studies on the accuracy of the two methods was
      assessed. RESULTS: VS had greater accuracy than VSTB. Both methods had a Sn and
      Sp>82%. The PPV of both methods was >97%, whereas that of NPV was <=44%. Males
      and recent graduates performed better than females and senior dentists when using
      VS and VSTB methods. CONCLUSIONS: It is questionable whether screening using VS
      or VSTB can ensure effective referral of children for treatment. Further studies
      are needed to assess other aspects of screening, including whether referred
      children actually seek care and whether screening improves children's oral
      health.

PMID- 25386633
TI  - Prevalence of static and dynamic dental malocclusion features in subgroups of
      temporomandibular disorder patients: Implications for the epidemiology of the TMD
      occlusion association.
AB  - OBJECTIVE: The hypothesis that dental malocclusions may be a risk factor for
      temporomandibular disorders (TMD) has been greatly debated in the literature.
      Whilst the association between features of dental occlusion and TMD has been
      proven weak, if existing, it seems that the transfer of such knowledge into
      clinical practice is yet to be completed. This study evaluated the prevalence of
      static and dynamic malocclusion features in a population of TMD patients and
      compared it with literature data on the general population. METHOD AND MATERIALS:
      A total of 625 consecutive TMD patients (75% female; aged 34.2 +/- 6.7 years,
      range 25-44 years) were examined and were clustered into four groups on the basis
      of pain absence (ie, disk displacement and/or arthrosis without pain), or pain
      presence within the muscles and/or the temporomandibular joint (TMJ). As for the
      occlusal features, posterior crossbite, excessive overbite, anterior open bite,
      excessive overjet, and molar and canine asymmetry were recorded as static
      malocclusion findings. Medio-/laterotrusive interferences and slide length from
      retruded contact position (RCP) to maximum intercuspation (MI) >= 2 mm were also
      recorded as dynamic malocclusion findings. The phi correlation coefficient
      assessed the strength of the correlation between each occlusal feature and the
      presence of pain-related TMD condition. RESULTS: No significant correlation was
      seen between the various malocclusion findings and the presence of any pain
      related TMD condition, with phi values ranging from -0.081 to +0.043 for molar
      asymmetry and laterotrusive interferences, respectively. The prevalence findings
      in this TMD population were within the range reported from general population
      studies. CONCLUSIONS: In adult subjects, static or dynamic malocclusion findings
      show similar prevalence irrespective of the presence of any specific pain-related
      TMD condition. Also, the prevalence values are similar to the available data at
      general population level. Based on the above, general practitioners should note
      that occlusal features may not be considered a discriminant factor for TMD.

PMID- 25386634
TI  - Surgical recommendations for the extraction of erupted maxillary third molars:
      landmarks emerging from a clinical study.
AB  - OBJECTIVE: This study evaluated the efficacy of an anatomicalradiologic- surgical
      protocol for the extraction of erupted maxillary third molars (EMTMs). METHODS
      AND MATERIALS: 166 EMTMs were extracted according to two different extraction
      techniques. Group 1 (G1, 97 teeth) was treated with the proposed protocol:
      multiple roots with forceps DG 117/DG 118; single roots with DG 250; tapered
      roots with DG 270; curved roots with Apexo 303 elevator. Group 2 (G2, 69 teeth)
      was treated with straight elevator and forceps DG 250 or DG 270. Extraction time
      and total number of complications (TNCs) were the main outcomes; TNCs were also
      divided in complications during the extraction (CDEs) and complications after the
      extraction (CAEs) as secondary outcomes. RESULTS: Differences between G1 and G2
      were detected for extraction time (146.8 vs 225.6 seconds; P < .05) and for
      complications (G1, 13.4% vs G2, 47.8%; P < .001). Multivariate analysis showed
      that extraction time and smoking habit were independent risk factors for TNCs (P
      < .001); furthermore, "not applying the proposed extraction protocol" increases
      almost 7 times (6.86; 95% CI, 1.41-33.32; P < .02) the possible onset of CAEs.
      CONCLUSION: The proposed protocol can be helpful for the general dental
      practitioner in planning the extraction of EMTMs, shortening the extraction time,
      and diminishing the complications, especially those occurring after the
      extraction.

PMID- 25386635
TI  - Enamel matrix protein derivative plus synthetic bone substitute for the treatment
      of mandibular Class II furcation defects: a case series.
AB  - OBJECTIVES: The aim of this study is to report on the treatment of mandibular
      Class II furcation defects with enamel matrix protein derivative (EMD) combined
      with a betaTCP/HA (beta-tricalcium phosphate/hydroxyapatite) alloplastic
      material. METHOD AND MATERIALS: Thirteen patients were selected. All patients
      were nonsmokers, systemically healthy, and diagnosed with chronic periodontitis;
      had not taken medications known to interfere with periodontal tissue health and
      healing; presented one Class II mandibular furcation defect with horizontal
      probing equal to or greater than 4 mm at buccal site. The clinical parameters
      evaluated were probing depth (PD), relative gingival margin position (RGMP),
      relative vertical clinical attachment level (RVCAL), and relative horizontal
      clinical attachment level (RHCAL). A paired Student t test was used to detect
      differences between the baseline and 6-month measurements, with the level of
      significance of .05. RESULTS: After 6 months, the treatment produced a
      statistically significant reduction in PD and a significant gain in RVCAL and
      RHCAL, but no observable change in RGMP. RVCAL ranged from 13.77 (+/- 1.31) at
      baseline to 12.15 (+/- 1.29) after 6 months, with a mean change of -1.62 +/- 1.00
      mm (P < .05). RHCAL ranged from 5.54 (+/- 0.75) to 2.92 (+/- 0.92), with a mean
      change of -2.62 +/- 0.63 mm (P < .05). After 6 months, 76.92% of the patients
      improved their diagnosis to Class I furcation defects while 23.08% remained as
      Class II. CONCLUSION: The present study has shown that positive clinical results
      may be expected from the combined treatment of Class II furcation defects with
      EMD and betaTCP/HA, especially considering the gain of horizontal attachment
      level. Despite this result, controlled clinical studies are needed to confirm our
      outcomes.

PMID- 25386636
TI  - Guest Editorial: It is time for the expansion of dentistry to include the care of
      individuals with special needs.

PMID- 25386637
TI  - Single step derivatization with CF3 enone of thiophene at ambient temperature to
      determine propellant grade hydrazines: a study by GC and GC-MS.
AB  - A simple, highly selective and rapid gas chromatography method (packed column
      with flame ionization detection) has been developed to determine hydrazine and
      monomethylhydrazine individually and for selective determination of hydrazine in
      the UH 25 mixture in organic medium. This method is based on the derivatization
      of hydrazine (at ambient temperature) with 1,1,1-trifluoro-4-(3-thienyl) (CF3
      enone) in the absence of catalyst/buffer which leads to the formation of
      corresponding pyrazolidine/pyrazoline/pyrazole. The organic derivatives thus
      formed are then detected and their presence is confirmed by GC-MS. The GC method
      provides good resolution between CF3 enone and its derivatives with a total
      analysis time of 20 min. The concentration of CF3 enone and derivatization time
      are optimized to determine hydrazines in the concentration range of 0.4 mM to 0.2
      M. The calibration curves based on peak areas of CF3 enone and its derivatives
      showed good linearity with r(2) ~ 0.999 for the working range and the precision
      was found to be less than 1% for hydrazine, MMH and hydrazine in UH25. The
      recovery was found by the standard addition method. Under the established
      conditions, limits of detection were 20 MUM for hydrazine, 10 MUM for MMH and 20
      MUM for hydrazine in UH25. The tolerance limit for interfering amines was also
      found. The advantage of this method is the selective detection and determination
      of hydrazine in the UH25 mixture as 1,1-dimethylhydrazine present in UH25 cannot
      be derivatized with CF3 enone. 

PMID- 25386638
TI  - Cardiovascular safety of stimulant medications.

PMID- 25386639
TI  - Relationship between neural rhythm generation disorders and physical disabilities
      in Parkinson's disease patients' walking.
AB  - Walking is generated by the interaction between neural rhythmic and physical
      activities. In fact, Parkinson's disease (PD), which is an example of disease,
      causes not only neural rhythm generation disorders but also physical
      disabilities. However, the relationship between neural rhythm generation
      disorders and physical disabilities has not been determined. The aim of this
      study was to identify the mechanism of gait rhythm generation. In former
      research, neural rhythm generation disorders in PD patients' walking were
      characterized by stride intervals, which are more variable and fluctuate
      randomly. The variability and fluctuation property were quantified using the
      coefficient of variation (CV) and scaling exponent alpha. Conversely, because
      walking is a dynamic process, postural reflex disorder (PRD) is considered the
      best way to estimate physical disabilities in walking. Therefore, we classified
      the severity of PRD using CV and alpha. Specifically, PD patients and healthy
      elderly were classified into three groups: no-PRD, mild-PRD, and obvious-PRD. We
      compared the contributions of CV and alpha to the accuracy of this
      classification. In this study, 45 PD patients and 17 healthy elderly people
      walked 200 m. The severity of PRD was determined using the modified Hoehn-Yahr
      scale (mH-Y). People with mH-Y scores of 2.5 and 3 had mild-PRD and obvious-PRD,
      respectively. As a result, CV differentiated no-PRD from PRD, indicating the
      correlation between CV and PRD. Considering that PRD is independent of neural
      rhythm generation, this result suggests the existence of feedback process from
      physical activities to neural rhythmic activities. Moreover, alpha differentiated
      obvious-PRD from mild-PRD. Considering alpha reflects the intensity of
      interaction between factors, this result suggests the change of the interaction.
      Therefore, the interaction between neural rhythmic and physical activities is
      thought to plays an important role for gait rhythm generation. These
      characteristics have potential to evaluate the symptoms of PD. 

PMID- 25386641
TI  - [Acute abdomen in children].

PMID- 25386640
TI  - Exploring the genetic basis of adaptation to high elevations in reptiles: a
      comparative transcriptome analysis of two toad-headed agamas (genus
      Phrynocephalus).
AB  - High elevation adaptation offers an excellent study system to understand the
      genetic basis of adaptive evolution. We acquired transcriptome sequences of two
      closely related lizards, Phrynocephalus przewalskii from low elevations and P.
      vlangalii from high elevations. Within a phylogenetic framework, we compared
      their genomic data along with green anole, chicken and Chinese softshell turtle,
      and identified candidate genes and functional categories that are potentially
      linked to adaptation to high elevation environments. More than 100 million
      sequence reads were generated for each species via Illumina sequencing. A de novo
      assembly produced 70,919 and 62,118 transcripts for P. przewalskii and P.
      vlangalii, respectively. Based on a well-established reptile phylogeny, we
      detected 143 positively selected genes (PSGs) along the P. vlangalii lineage from
      the 7,012 putative orthologs using a branch-site model. Furthermore, ten GO
      categories and one KEGG pathway that are over-represented by PSGs were
      recognized. In addition, 58 GO categories were revealed to have elevated
      evolutionary rates along the P. vlangalii lineage relative to P. przewalskii.
      These functional analyses further filter out PSGs that are most likely involved
      in the adaptation process to high elevations. Among them, ADAM17, MD, and HSP90B1
      likely contributed to response to hypoxia, and POLK likely contributed to DNA
      repair. Many other candidate genes involved in gene expression and metabolism
      were also identified. Genome-wide scan for candidate genes may serve as the first
      step to explore the genetic basis of high elevation adaptation. Detailed
      comparative study and functional verification are needed to solidify any
      conclusions. High elevation adaptation requires coordinated changes in multiple
      genes that involve various physiological and biochemical pathways; we hope that
      our genetic studies will provide useful directions for future physiological or
      molecular studies in reptiles as well as other poikilothermic species. 

PMID- 25386642
TI  - [New method of treating achalasia is now being tested. Minimally Invasive POEM
      has produced promising results so far].
AB  - Achalasia of the cardia is a motor disorder of the esophagus and lower esophageal
      sphincter with dysphagia as the dominating symptom. The diagnosis is based on
      esophageal manometry and barium swallow. During work-up dysphagia of other origin
      should be excluded by endoscopy. Standard treatment of achalasia today is
      laparoscopic esophagogastromyotomy with partial fundoplication or pneumatic
      dilatation of the lower esophageal sphincter. POEM (PerOral Endoscopic Myotomy),
      a new minimally invasive technique, has recently been introduced in Sweden. So
      far, 45 patients have been treated. POEM is currently being compared with
      laparoscopic esophagogastromyotomy within a European randomized multicenter
      study. 

PMID- 25386643
TI  - [Treatment of achalasia--from whale bone to poem. The biggest success so far
      within transluminal surgery].

PMID- 25386644
TI  - ["Spice"--synthetic cannabinoids with dangerous effects].
AB  - Synthetic cannabinoids are a large group of chemicals functionally related to
      delta-9-tetrahydrocannabinol (THC) found in Cannabis sativa. These compounds are
      full agonists on cannabinoid receptors, therefore more potent than THC. Products
      marketed over the Internet intended for abuse usually consist of dried inert
      plant material sprayed with different kinds of cannabinoids. Smoking is the most
      common route of administration. In Sweden commercially available products are
      usually labeled "spice". A case concerning a young male with convulsions and
      acute kidney failure requiring temporary dialysis is presented. Other reported
      serious effects of this group of substances are acute psychosis, unconsciousness,
      cardiac ischemia, seizures and stroke. The vendors are very aware of the legal
      situation in each country and adjust their supply according to current narcotics
      classifications. New, previously unknown cannabinoids are constantly appearing on
      the market. 

PMID- 25386645
TI  - [Communication training for the medical staff can improve patient satisfaction].
AB  - This literature review presents results of research on communication skills
      training (CST) of medical staff and its effect on patients. The 27 studies
      identified by a search in PubMed and Cochrane databases showed considerable
      heterogeneity in interventions, methods and study length. Most studies found a
      positive effect on patient satisfaction after the staff had participated in CST.
      Furthermore, there are indications that CST has an effect on other patient
      outcomes. Increasing the patient-centeredness in the consultation results in
      improved patient satisfaction and moreover has positive effects on psychological
      and physiological factors, such as improved function status and reduction in pain
      and blood pressure. Overall, we conclude that CST for health staff tends to
      improve patient satisfaction and other patient outcomes. The results of the
      studies are ambiguous, however the majority show positive results. 

PMID- 25386646
TI  - Effect of the CALHM1 G330D and R154H human variants on the control of cytosolic
      Ca2+ and Abeta levels.
AB  - CALHM1 is a plasma membrane voltage-gated Ca2+-permeable ion channel that
      controls amyloid-beta (Abeta) metabolism and is potentially involved in the onset
      of Alzheimer's disease (AD). Recently, Rubio-Moscardo et al. (PLoS One (2013) 8:
      e74203) reported the identification of two CALHM1 variants, G330D and R154H, in
      early-onset AD (EOAD) patients. The authors provided evidence that these two
      human variants were rare and resulted in a complete loss of CALHM1 function.
      Recent publicly available large-scale exome sequencing data confirmed that R154H
      is a rare CALHM1 variant (minor allele frequency (MAF)  = 0.015%), but that G330D
      is not (MAF  = 3.5% in an African American cohort). Here, we show that both
      CALHM1 variants exhibited gating and permeation properties indistinguishable from
      wild-type CALHM1 when expressed in Xenopus oocytes. While there was also no
      effect of the G330D mutation on Ca2+ uptake by CALHM1 in transfected mammalian
      cells, the R154H mutation was associated with defects in the control by CALHM1 of
      both Ca2+ uptake and Abeta levels in this cell system. Together, our data show
      that the frequent CALHM1 G330D variant has no obvious functional consequences and
      is therefore unlikely to contribute to EOAD. Our data also demonstrate that the
      rare R154H variant interferes with CALHM1 control of cytosolic Ca2+ and Abeta
      accumulation. While these results strengthen the notion that CALHM1 influences
      Abeta metabolism, further investigation will be required to determine whether
      CALHM1 R154H, or other natural variants in CALHM1, is/are associated with EOAD. 

PMID- 25386647
TI  - Thermodynamic system drift in protein evolution.
AB  - Proteins from thermophiles are generally more thermostable than their mesophilic
      homologs, but little is known about the evolutionary process driving these
      differences. Here we attempt to understand how the diverse thermostabilities of
      bacterial ribonuclease H1 (RNH) proteins evolved. RNH proteins from Thermus
      thermophilus (ttRNH) and Escherichia coli (ecRNH) share similar structures but
      differ in melting temperature (T(m)) by 20  degrees C. ttRNH's greater stability
      is caused in part by the presence of residual structure in the unfolded state,
      which results in a low heat capacity of unfolding (DeltaCp) relative to ecRNH. We
      first characterized RNH proteins from a variety of extant bacteria and found that
      Tm correlates with the species' growth temperatures, consistent with
      environmental selection for stability. We then used ancestral sequence
      reconstruction to statistically infer evolutionary intermediates along lineages
      leading to ecRNH and ttRNH from their common ancestor, which existed
      approximately 3 billion years ago. Finally, we synthesized and experimentally
      characterized these intermediates. The shared ancestor has a melting temperature
      between those of ttRNH and ecRNH; the T(m)s of intermediate ancestors along the
      ttRNH lineage increased gradually over time, while the ecRNH lineage exhibited an
      abrupt drop in Tm followed by relatively little change. To determine whether the
      underlying mechanisms for thermostability correlate with the changes in T(m), we
      measured the thermodynamic basis for stabilization--DeltaCp and other
      thermodynamic parameters--for each of the ancestors. We observed that, while the
      T(m) changes smoothly, the mechanistic basis for stability fluctuates over
      evolutionary time. Thus, even while overall stability appears to be strongly
      driven by selection, the proteins explored a wide variety of mechanisms of
      stabilization, a phenomenon we call "thermodynamic system drift." This suggests
      that even on lineages with strong selection to increase stability, proteins have
      wide latitude to explore sequence space, generating biophysical diversity and
      potentially opening new evolutionary pathways.

PMID- 25386648
TI  - Inactivation of TRPM2 channels by extracellular divalent copper.
AB  - Cu2+ is an essential metal ion that plays a critical role in the regulation of a
      number of ion channels and receptors in addition to acting as a cofactor in a
      variety of enzymes. Here, we showed that human melastatin transient receptor
      potential 2 (hTRPM2) channel is sensitive to inhibition by extracellular Cu2+.
      Cu2+ at concentrations as low as 3 uM inhibited the hTRPM2 channel completely and
      irreversibly upon washing or using Cu2+ chelators, suggesting channel
      inactivation. The Cu2+-induced inactivation was similar when the channels
      conducted inward or outward currents, indicating the permeating ions had little
      effect on Cu2+-induced inactivation. Furthermore, Cu2+ had no effect on singe
      channel conductance. Alanine substitution by site-directed mutagenesis of His995
      in the pore-forming region strongly attenuated Cu2+-induced channel inactivation,
      and mutation of several other pore residues to alanine altered the kinetics of
      channel inactivation by Cu2+. In addition, while introduction of the P1018L
      mutation is known to result in channel inactivation, exposure to Cu2+ accelerated
      the inactivation of this mutant channel. In contrast with the hTRPM2, the mouse
      TRPM2 (mTRPM2) channel, which contains glutamine at the position equivalent to
      His995, was insensitive to Cu2+. Replacement of His995 with glutamine in the
      hTRPM2 conferred loss of Cu2+-induced channel inactivation. Taken together, these
      results suggest that Cu2+ inactivates the hTRPM2 channel by interacting with the
      outer pore region. Our results also indicate that the amino acid residue
      difference in this region gives rise to species-dependent effect by Cu2+ on the
      human and mouse TRPM2 channels. 

PMID- 25386649
TI  - A three-dimensional computational model of collagen network mechanics.
AB  - Extracellular matrix (ECM) strongly influences cellular behaviors, including cell
      proliferation, adhesion, and particularly migration. In cancer, the rigidity of
      the stromal collagen environment is thought to control tumor aggressiveness, and
      collagen alignment has been linked to tumor cell invasion. While the mechanical
      properties of collagen at both the single fiber scale and the bulk gel scale are
      quite well studied, how the fiber network responds to local stress or
      deformation, both structurally and mechanically, is poorly understood. This
      intermediate scale knowledge is important to understanding cell-ECM interactions
      and is the focus of this study. We have developed a three-dimensional elastic
      collagen fiber network model (bead-and-spring model) and studied fiber network
      behaviors for various biophysical conditions: collagen density, crosslinker
      strength, crosslinker density, and fiber orientation (random vs. prealigned). We
      found the best-fit crosslinker parameter values using shear simulation tests in a
      small strain region. Using this calibrated collagen model, we simulated both
      shear and tensile tests in a large linear strain region for different network
      geometry conditions. The results suggest that network geometry is a key
      determinant of the mechanical properties of the fiber network. We further
      demonstrated how the fiber network structure and mechanics evolves with a local
      formation, mimicking the effect of pulling by a pseudopod during cell migration.
      Our computational fiber network model is a step toward a full biomechanical model
      of cellular behaviors in various ECM conditions. 

PMID- 25386650
TI  - Cis-regulatory control of the nuclear receptor Coup-TF gene in the sea urchin
      Paracentrotus lividus embryo.
AB  - Coup-TF, an orphan member of the nuclear receptor super family, has a fundamental
      role in the development of metazoan embryos. The study of the gene's regulatory
      circuit in the sea urchin embryo will facilitate the placement of this
      transcription factor in the well-studied embryonic Gene Regulatory Network (GRN).
      The Paracentrotus lividus Coup-TF gene (PlCoup-TF) is expressed throughout
      embryonic development preferentially in the oral ectoderm of the gastrula and the
      ciliary band of the pluteus stage. Two overlapping lambda genomic clones,
      containing three exons and upstream sequences of PlCoup-TF, were isolated from a
      genomic library. The transcription initiation site was determined and 5'
      deletions and individual segments of a 1930 bp upstream region were placed ahead
      of a GFP reporter cassette and injected into fertilized P.lividus eggs. Module a
      (-532 to -232), was necessary and sufficient to confer ciliary band expression to
      the reporter. Comparison of P.lividus and Strongylocentrotus purpuratus upstream
      Coup-TF sequences, revealed considerable conservation, but none within module a.
      5' and internal deletions into module a, defined a smaller region that confers
      ciliary band specific expression. Putative regulatory cis-acting elements (RE1,
      RE2 and RE3) within module a, were specifically bound by proteins in sea urchin
      embryonic nuclear extracts. Site-specific mutagenesis of these elements resulted
      in loss of reporter activity (RE1) or ectopic expression (RE2, RE3). It is
      proposed that sea urchin transcription factors, which bind these three regulatory
      sites, are necessary for spatial and quantitative regulation of the PlCoup-TF
      gene at pluteus stage sea urchin embryos. These findings lead to the future
      identification of these factors and to the hierarchical positioning of PlCoup-TF
      within the embryonic GRN. 

PMID- 25386651
TI  - Modulating the structure of EGFR with UV light: new possibilities in cancer
      therapy.
AB  - The epidermal growth factor receptor (EGFR) is a member of the ErbB family of
      receptor tyrosine kinases. EGFR is activated upon binding to e.g. epidermal
      growth factor (EGF), leading to cell survival, proliferation and migration. EGFR
      overactivation is associated with tumor progression. We have previously shown
      that low dose UVB illumination of cancer cells overexpressing EGFR prior to
      adding EGF halted the EGFR signaling pathway. We here show that UVB illumination
      of the extracellular domain of EGFR (sEGFR) induces protein conformational
      changes, disulphide bridge breakage and formation of tryptophan and tyrosine
      photoproducts such as dityrosine, N-formylkynurenine and kynurenine. Fluorescence
      spectroscopy, circular dichroism and thermal studies confirm the occurrence of
      conformational changes. An immunoassay has confirmed that UVB light induces
      structural changes in the EGF binding site. A monoclonal antibody which competes
      with EGF for binding sEGFR was used. We report clear evidence that UVB light
      induces structural changes in EGFR that impairs the correct binding of an EGFR
      specific antibody that competes with EGF for binding EGFR, confirming that the 3D
      structure of the EGFR binding domain suffered conformational changes upon UV
      illumination. The irradiance used is in the same order of magnitude as the
      integrated intensity in the solar UVB range. The new photonic technology disables
      a key receptor and is most likely applicable to the treatment of various types of
      cancer, alone or in combination with other therapies. 

PMID- 25386652
TI  - The VELVET A orthologue VEL1 of Trichoderma reesei regulates fungal development
      and is essential for cellulase gene expression.
AB  - Trichoderma reesei is the industrial producer of cellulases and hemicellulases
      for biorefinery processes. Their expression is obligatorily dependent on the
      function of the protein methyltransferase LAE1. The Aspergillus nidulans
      orthologue of LAE1--LaeA--is part of the VELVET protein complex consisting of
      LaeA, VeA and VelB that regulates secondary metabolism and sexual as well as
      asexual reproduction. Here we have therefore investigated the function of VEL1,
      the T. reesei orthologue of A. nidulans VeA. Deletion of the T. reesei vel1 locus
      causes a complete and light-independent loss of conidiation, and impairs
      formation of perithecia. Deletion of vel1 also alters hyphal morphology towards
      hyperbranching and formation of thicker filaments, and with consequently reduced
      growth rates. Growth on lactose as a sole carbon source, however, is even more
      strongly reduced and growth on cellulose as a sole carbon source eliminated.
      Consistent with these findings, deletion of vel1 completely impaired the
      expression of cellulases, xylanases and the cellulase regulator XYR1 on lactose
      as a cellulase inducing carbon source, but also in resting mycelia with sophorose
      as inducer. Our data show that in T. reesei VEL1 controls sexual and asexual
      development, and this effect is independent of light. VEL1 is also essential for
      cellulase gene expression, which is consistent with the assumption that their
      regulation by LAE1 occurs by the VELVET complex.

PMID- 25386653
TI  - Corticosteroids and pediatric septic shock outcomes: a risk stratified analysis.
AB  - BACKGROUND: The potential benefits of corticosteroids for septic shock may depend
      on initial mortality risk. OBJECTIVE: We determined associations between
      corticosteroids and outcomes in children with septic shock who were stratified by
      initial mortality risk. METHODS: We conducted a retrospective analysis of an
      ongoing, multi-center pediatric septic shock clinical and biological database.
      Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects
      were stratified into three initial mortality risk strata (low, intermediate, and
      high). Subjects receiving corticosteroids during the initial 7 days of admission
      (n = 252) were compared to subjects who did not receive corticosteroids (n =
      244). Logistic regression was used to model the effects of corticosteroids on 28
      day mortality and complicated course, defined as death within 28 days or
      persistence of two or more organ failures at 7 days. RESULTS: Subjects who
      received corticosteroids had greater organ failure burden, higher illness
      severity, higher mortality, and a greater requirement for vasoactive medications,
      compared to subjects who did not receive corticosteroids. PERSEVERE-based
      mortality risk did not differ between the two groups. For the entire cohort,
      corticosteroids were associated with increased risk of mortality (OR 2.3, 95% CI
      1.3-4.0, p = 0.004) and a complicated course (OR 1.7, 95% CI 1.1-2.5, p = 0.012).
      Within each PERSEVERE-based stratum, corticosteroid administration was not
      associated with improved outcomes. Similarly, corticosteroid administration was
      not associated with improved outcomes among patients with no comorbidities, nor
      in groups of patients stratified by PRISM. CONCLUSIONS: Risk stratified analysis
      failed to demonstrate any benefit from corticosteroids in this pediatric septic
      shock cohort.

PMID- 25386654
TI  - Identification of novel knockout targets for improving terpenoids biosynthesis in
      Saccharomyces cerevisiae.
AB  - Many terpenoids have important pharmacological activity and commercial value;
      however, application of these terpenoids is often limited by problems associated
      with the production of sufficient amounts of these molecules. The use of
      Saccharomyces cerevisiae (S. cerevisiae) for the production of heterologous
      terpenoids has achieved some success. The objective of this study was to identify
      S. cerevisiae knockout targets for improving the synthesis of heterologous
      terpeniods. On the basis of computational analysis of the S. cerevisiae metabolic
      network, we identified the knockout sites with the potential to promote terpenoid
      production and the corresponding single mutant was constructed by molecular
      manipulations. The growth rates of these strains were measured and the results
      indicated that the gene deletion had no adverse effects. Using the expression of
      amorphadiene biosynthesis as a testing model, the gene deletion was assessed for
      its effect on the production of exogenous terpenoids. The results showed that the
      dysfunction of most genes led to increased production of amorphadiene. The yield
      of amorphadiene produced by most single mutants was 8-10-fold greater compared to
      the wild type, indicating that the knockout sites can be engineered to promote
      the synthesis of exogenous terpenoids. 

PMID- 25386655
TI  - Spatial analysis of pulmonary tuberculosis in Antananarivo Madagascar:
      tuberculosis-related knowledge, attitude and practice.
AB  - INTRODUCTION: Tuberculosis infection may remain latent, but the disease is
      nevertheless a serious public health issue. Various epidemiological studies on
      pulmonary tuberculosis have considered the spatial component and taken it into
      account, revealing the tendency of this disease to cluster in particular
      locations. The aim was to assess the contribution of Knowledge Attitude and
      Practice (KAP) to the distribution of tuberculosis and to provide information for
      the improvement of the National Tuberculosis Program. METHODS: We investigated
      the role of KAP to distribution patterns of pulmonary tuberculosis in
      Antananarivo. First, we performed spatial scanning of tuberculosis aggregation
      among permanent cases resident in Antananarivo Urban Township using the Kulldorff
      method, and then we carried out a quantitative study on KAP, involving TB
      patients. The KAP study in the population was based on qualitative methods with
      focus groups. RESULTS: The disease still clusters in the same districts
      identified in the previous study. The principal cluster covered 22 neighborhoods.
      Most of them are part of the first district. A secondary cluster was found,
      involving 18 neighborhoods in the sixth district and two neighborhoods in the
      fifth. The relative risk was respectively 1.7 (p<10-6) in the principal cluster
      and 1.6 (p<10-3) in the secondary cluster. Our study showed that more was known
      about TB symptoms than about the duration of the disease or free treatment.
      Knowledge about TB was limited to that acquired at school or from relatives with
      TB. The attitude and practices of patients and the population in general
      indicated that there is still a stigma attached to tuberculosis. CONCLUSION: This
      type of survey can be conducted in remote zones where the tuberculosis-related
      KAP of the TB patients and the general population is less known or not
      documented; the findings could be used to adapt control measures to the local
      particularities.

PMID- 25386656
TI  - Looking out for cancer stem cells' properties: the value-driving role of CD44 for
      personalized medicines.
AB  - The expression of CD44 tags cells with stemness-associated properties (cancer
      initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a
      cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a
      crucial role in tumorigenesis. The CD44 receptor enables the cell to respond to
      changes in tumor microenvironment, promoting several signaling events related to
      tumor initiation, progression and fixation in distant host tissues. Although the
      contribution of this transmembrane protein in gene regulation remains unclear,
      its overexpression in adenocarcinomas, mostly supported by microRNA (miR)
      mediated upregulation of target mRNA, is widely accepted. Herein, we gather the
      evidence that CD44 is one of the most predominant markers of malignant cells and
      may be found in diverse phenotypes associated with tumor progression.
      Additionally, CD44 tumor receptors were found to have different roles at a
      transcriptional level. Thus, innovative therapeutic strategies should rely
      heavily on its metastasis-promoting ability. Furthermore, the concept of
      selectively targeting cell sub-populations may be used to develop specific
      therapeutic and/or diagnostic systems. An approach based on targeting CD44+ cells
      might provide a strategy to design guided-therapeutic systems against multiple
      malignant cells including putative CSC.

PMID- 25386657
TI  - Combining anti-ERBB3 antibodies specific for domain I and domain III enhances the
      anti-tumor activity over the individual monoclonal antibodies.
AB  - BACKGROUND: Inappropriate signaling through the epidermal growth factor receptor
      family (EGFR1/ERBB1, ERBB2/HER2, ERBB3/HER3, and ERBB4/HER4) of receptor tyrosine
      kinases leads to unregulated activation of multiple downstream signaling pathways
      that are linked to cancer formation and progression. In particular, ERBB3 plays a
      critical role in linking ERBB signaling to the phosphoinositide 3-kinase and Akt
      signaling pathway and increased levels of ERBB3-dependent signaling is also
      increasingly recognized as a mechanism for acquired resistance to ERBB-targeted
      therapies. METHODS: We had previously reported the isolation of a panel of anti
      ERBB3 single-chain Fv antibodies through use of phage-display technology. In the
      current study scFv specific for domain I (F4) and domain III (A5) were converted
      into human IgG1 formats and analyzed for efficacy. RESULTS: Treatment of cells
      with an oligoclonal mixture of the A5/F4 IgGs appeared more effective at blocking
      both ligand-induced and ligand-independent signaling through ERBB3 than either
      single IgG alone. This correlated with improved ability to inhibit the cell
      growth both as a single agent and in combination with other ERBB-targeted
      therapies. Treatment of NCI-N87 tumor xenografts with the A5/F4 oligoclonal led
      to a statistically significant decrease in tumor growth rate that was further
      enhanced in combination with trastuzumab. CONCLUSION: These results suggest that
      an oligoclonal antibody mixture may be a more effective approach to downregulate
      ERBB3-dependent signaling.

PMID- 25386658
TI  - Mean platelet volume (MPV) predicts middle distance running performance.
AB  - BACKGROUND: Running economy and performance in middle distance running depend on
      several physiological factors, which include anthropometric variables, functional
      characteristics, training volume and intensity. Since little information is
      available about hematological predictors of middle distance running time, we
      investigated whether some hematological parameters may be associated with middle
      distance running performance in a large sample of recreational runners. METHODS:
      The study population consisted in 43 amateur runners (15 females, 28 males;
      median age 47 years), who successfully concluded a 21.1 km half-marathon at 75
      85% of their maximal aerobic power (VO2max). Whole blood was collected 10 min
      before the run started and immediately thereafter, and hematological testing was
      completed within 2 hours after sample collection. RESULTS: The values of
      lymphocytes and eosinophils exhibited a significant decrease compared to pre-run
      values, whereas those of mean corpuscular volume (MCV), platelets, mean platelet
      volume (MPV), white blood cells (WBCs), neutrophils and monocytes were
      significantly increased after the run. In univariate analysis, significant
      associations with running time were found for pre-run values of hematocrit,
      hemoglobin, mean corpuscular hemoglobin (MCH), red blood cell distribution width
      (RDW), MPV, reticulocyte hemoglobin concentration (RetCHR), and post-run values
      of MCH, RDW, MPV, monocytes and RetCHR. In multivariate analysis, in which
      running time was entered as dependent variable whereas age, sex, blood lactate,
      body mass index, VO2max, mean training regimen and the hematological parameters
      significantly associated with running performance in univariate analysis were
      entered as independent variables, only MPV values before and after the trial
      remained significantly associated with running time. After adjustment for
      platelet count, the MPV value before the run (p = 0.042), but not thereafter (p =
      0.247), remained significantly associated with running performance. CONCLUSION:
      The significant association between baseline MPV and running time suggest that
      hyperactive platelets may exert some pleiotropic effects on endurance
      performance.

PMID- 25386659
TI  - The relevance of external quality assessment for molecular testing for ALK
      positive non-small cell lung cancer: results from two pilot rounds show room for
      optimization.
AB  - BACKGROUND AND PURPOSE: Molecular profiling should be performed on all advanced
      non-small cell lung cancer with non-squamous histology to allow treatment
      selection. Currently, this should include EGFR mutation testing and testing for
      ALK rearrangements. ROS1 is another emerging target. ALK rearrangement status is
      a critical biomarker to predict response to tyrosine kinase inhibitors such as
      crizotinib. To promote high quality testing in non-small cell lung cancer, the
      European Society of Pathology has introduced an external quality assessment
      scheme. This article summarizes the results of the first two pilot rounds
      organized in 2012-2013. MATERIALS AND METHODS: Tissue microarray slides
      consisting of cell-lines and resection specimens were distributed with the
      request for routine ALK testing using IHC or FISH. Participation in ALK FISH
      testing included the interpretation of four digital FISH images. RESULTS: Data
      from 173 different laboratories was obtained. Results demonstrate decreased error
      rates in the second round for both ALK FISH and ALK IHC, although the error rates
      were still high and the need for external quality assessment in laboratories
      performing ALK testing is evident. Error rates obtained by FISH were lower than
      by IHC. The lowest error rates were observed for the interpretation of digital
      FISH images. CONCLUSION: There was a large variety in FISH enumeration practices.
      Based on the results from this study, recommendations for the methodology,
      analysis, interpretation and result reporting were issued. External quality
      assessment is a crucial element to improve the quality of molecular testing.

PMID- 25386660
TI  - Multiple thyrotropin beta-subunit and thyrotropin receptor-related genes arose
      during vertebrate evolution.
AB  - Thyroid-stimulating hormone (TSH) is composed of a specific beta subunit and an
      alpha subunit that is shared with the two pituitary gonadotropins. The three beta
      subunits derive from a common ancestral gene through two genome duplications (1R
      and 2R) that took place before the radiation of vertebrates. Analysis of genomic
      data from phylogenetically relevant species allowed us to identify an additional
      Tshbeta subunit-related gene that was generated through 2R. This gene, named
      Tshbeta2, present in cartilaginous fish, little skate and elephant shark, and in
      early lobe-finned fish, coelacanth and lungfish, was lost in ray-finned fish and
      tetrapods. The absence of a second type of TSH receptor (Tshr) gene in these
      species suggests that both TSHs act through the same receptor. A novel Tshbeta
      sister gene, named Tshbeta3, was generated through the third genomic duplication
      (3R) that occurred early in the teleost lineage. Tshbeta3 is present in most
      teleost groups but was lostin tedraodontiforms. The 3R also generated a second
      Tshr, named Tshrb. Interestingly, the new Tshrb was translocated from its
      original chromosomic position after the emergence of eels and was then maintained
      in its new position. Tshrb was lost in tetraodontiforms and in ostariophysians
      including zebrafish although the latter species have two TSHs, suggesting that
      TSHRb may be dispensable. The tissue distribution of duplicated Tshbetas and
      Tshrs was studied in the European eel. The endocrine thyrotropic function in the
      eel would be essentially mediated by the classical Tshbeta and Tshra, which are
      mainly expressed in the pituitary and thyroid, respectively. Tshbeta3 and Tshrb
      showed a similar distribution pattern in the brain, pituitary, ovary and adipose
      tissue, suggesting a possible paracrine/autocrine mode of action in these non
      thyroidal tissues. Further studies will be needed to determine the binding
      specificity of the two receptors and how these two TSH systems are interrelated. 

PMID- 25386662
TI  - Porcine Dermis and Pericardium-Based, Non-Cross-Linked Materials Induce
      Multinucleated Giant Cells After Their In Vivo Implantation: A Physiological
      Reaction?
AB  - The present study analyzed the tissue reaction to 2 novel porcine-derived
      collagen materials: pericardium versus dermis. By means of the subcutaneous
      implantation model in mice, the tissue reactions were investigated at 5 time
      points: 3, 10, 15, 30, and 60 days after implantation. Histologic, histochemical,
      immunhistologic, and histomorphometric analysis methodologies were applied. The
      dermis-derived material underwent an early degradation while inducing mononuclear
      cells together with some multinucleated giant cells and mild vascularization. The
      pericardium-derived membrane induced 2 different cellular tissue reactions. The
      compact surface induced mononuclear cells and multinucleated giant cells, and
      underwent a complete degradation until day 30. The spongy surface of the membrane
      induced mainly mononuclear cells, and served as a stable barrier membrane for up
      to 60 days. No transmembranous vascularization was observed within the spongy
      material surface layer. The present data demonstrate the diversity of the
      cellular tissue reaction toward collagen-based materials from different tissues.
      Furthermore, it became obvious that the presence of multinucleated giant cells
      was associated with the material breakdown/degradation and vascularization.
      Further clinical data are necessary to assess extent to which the presence of
      multinucleated giant cells observed here will influence the materials stability,
      integration, and, correspondingly, tissue regeneration within human tissue. 

PMID- 25386661
TI  - Effects of the use of assisted reproductive technologies and an obesogenic
      environment on resistance artery function and diabetes biomarkers in mice
      offspring.
AB  - Maternal obesity affects the incidence of cardiovascular disease and diabetes in
      offspring. Also the use of assisted reproductive technologies (ART) has been
      associated with cardiovascular deficiencies in offspring. Obese women often
      suffer from infertility and use ART to achieve a pregnancy, but the combined
      effects of maternal obesity and ART on cardiovascular health and incidence of
      diabetes in the offspring is not known. Here, we report the effects of the use of
      ART within an obesogenic environment, consisting of feeding a western diet (WD)
      to dams and offspring, on resistance artery function and presence of diabetes
      biomarkers in juvenile mice offspring. Our results indicate that WD and ART
      interacted to induce endothelial dysfunction in mesenteric resistance arteries
      isolated from 7-week-old mice offspring. This was determined by presence of a
      reduced acetylcholine-induced dilation compared to controls. The arteries from
      these WD-ART mice also had greater wall cross-sectional areas and wall to lumen
      ratios indicative of vascular hypertrophic remodeling. Of the diabetes biomarkers
      measured, only resistin was affected by a WD*ART interaction. Serum resistin was
      significantly greater in WD-ART offspring compared to controls. Diet and sex
      effects were observed in other diabetes biomarkers. Our conclusion is that in
      mice the use of ART within an obesogenic environment interacts to favor the
      development of endothelial dysfunction in the resistance arteries of juvenile
      offspring, while having marginal effects on diabetes biomarkers. 

PMID- 25386663
TI  - The small-molecule inhibitor selectivity between IKKalpha and IKKbeta kinases in
      NF-kappaB signaling pathway.
AB  - The enzyme complex IkappaB kinase (IKK) is an essential activator of NF-kappaB
      signaling pathway involved in propagating the cellular response to inflammation.
      The complex contains two functional subunits IKKalpha and IKKbeta, which are
      structurally conserved kinases and selective inhibition of them would result in
      distinct biological effects. However, most existing IKK inhibitors show moderate
      or high promiscuity for the two homologous kinases. Understanding of the
      molecular mechanism and biological implication underlying the specific
      interactions in IKK-ligand recognition is thus fundamentally important for the
      rational design of selective IKK inhibitors. In the current work, we integrated
      molecular docking, quantum mechanics/molecular mechanics calculation and Poisson
      Boltzmann/surface area analysis to investigate the structural basis and energetic
      property of the selective binding of small-molecule ligands to IKKalpha and
      IKKbeta. It was found that the selectivity is primarily determined by the size
      and topology difference in ATP-binding pocket of IKKalpha and IKKbeta kinase
      domains; bulky inhibitor molecules commonly have, respectively, low and
      appropriate affinities towards IKKalpha and IKKbeta, and thus exhibit relatively
      high selectivity for IKKbeta over IKKalpha, whereas small ligands can only bind
      weakly to both the two kinases with low selectivity. In addition, the
      conformation, arrangement and distribution of residues in IKK pockets are also
      responsible for constituting the exquisite specificity of ligand binding to
      KKalpha and IKKbeta. Next, a novel quantitative structure-selectivity
      relationship model was developed to characterize the relative contribution of
      each kinase residue to inhibitor selectivity and to predict the selectivity and
      specificity for a number of known IKK inhibitors. Results showed that the active
      site residues contribute significantly to the selectivity by directly interacting
      with inhibitor ligands, while those protein portions far away from the kinase
      active sites may also play an important role in determining the selectivity
      through long-range non-bonded forces and indirect allosteric effect. 

PMID- 25386664
TI  - Differences in ground reaction forces and shock impacts between nordic walking
      and walking.
AB  - The regular practice of Nordic walking (NW) has increased in recent years, in
      part thanks to the health benefits described by the scientific literature.
      However, there is no consensus on the effects of shock-impact absorption during
      its practice. PURPOSE: The aim of this study was to compare the levels of impact
      and ground reaction forces (GRF) between NW and walking (W). METHOD: Twenty
      physically active and experienced participants were assessed using a dynamometric
      platform and accelerometry analysis. RESULTS: The results show statistically
      significantly higher levels of acceleration in the tibia (12%) and head (21%)
      during NW compared with W. Equally, GRF were significantly higher (27%) at the
      instant of strike compared with W, and a reduction of the forces at the instant
      of takeoff (8%) was observed. CONCLUSIONS: During NW, shock impacts and GRF
      levels increased compared with W, an aspect that should be considered when
      prescribing health improvement programs.

PMID- 25386666
TI  - Aerobic physical exercise for adult patients with haematological malignancies.
AB  - BACKGROUND: Although people with haematological malignancies have to endure long
      phases of therapy and immobility which is known to diminish their physical
      performance level, the advice to rest and avoid intensive exercises is still
      common practice. This recommendation is partly due to the severe anaemia and
      thrombocytopenia from which many patients suffer. The inability to perform
      activities of daily living restricts them, diminishes their quality of life and
      can influence medical therapy. OBJECTIVES: To evaluate the efficacy, safety and
      feasibility of aerobic physical exercise for adults suffering from haematological
      malignancies. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library, 2014, Issue 1) and MEDLINE
      (1950 to January 2014) as well as conference proceedings for randomised
      controlled trials (RCTs). SELECTION CRITERIA: We included RCTs comparing an
      aerobic physical exercise intervention, intending to improve the oxygen system,
      in addition to standard care with standard care only for adults suffering from
      haematological malignancies. We also included studies that evaluated aerobic
      exercise in addition to strength training. We excluded studies that investigated
      the effect of training programmes that were composed of yoga, tai chi chuan,
      qigong or similar types of exercise. We also excluded studies exploring the
      influence of strength training without additive aerobic exercise. Additionally,
      we excluded studies assessing outcomes without any clinical impact. DATA
      COLLECTION AND ANALYSIS: Two review authors independently screened search
      results, extracted data and assessed the quality of trials. We used risk ratios
      (RRs) for adverse events and 100-day survival, standardised mean differences for
      quality of life (QoL), fatigue, and physical performance, and mean differences
      for anthropometric measurements. MAIN RESULTS: Our search strategies identified
      1518 potentially relevant references. Of these, we included nine RCTs involving
      818 participants. The potential risk of bias in these trials is unclear, due to
      poor reporting.The majority of participants suffered from acute lymphoblastic
      leukaemia (ALL), acute myeloid leukaemia (AML), malignant lymphoma and multiple
      myeloma, and six trials randomised people receiving stem cell transplantation.
      Mostly, the exercise intervention consisted of various walking intervention
      programmes with different duration and intensity levels.Our primary endpoint of
      overall survival (OS) was not analysed in any of the included trials, but three
      trials reported deceased participants during the course of the study or during
      the first 100 days. There is no evidence for a difference between participants
      exercising and those in the control group (RR 0.93; 95% CI 0.59 to 1.47; P =
      0.75; 3 trials, 269 participants, moderate quality of evidence).Four trials
      analysed the influence of exercise intervention on quality of life (QoL).
      Excluding one trial with serious baseline imbalances, physical exercise improves
      QoL (SMD 0.26; 95% CI 0.03 to 0.49; P = 0.03; 3 trials, 291 participants, low
      quality of evidence). This positive effect of exercise was also found in the
      subscales physical functioning (SMD 0.33; 95% CI 0.13 to 0.52; P = 0.0009; 4
      trials, 422 participants, moderate quality of evidence) and depression (SMD 0.25;
      95% CI -0.00 to 0.50; P = 0.05; 3 trials, 249 participants, low quality of
      evidence). However, there is no evidence for a difference between additional
      exercise and standard treatment for the subscale anxiety (SMD -0.18; 95% CI -0.64
      to 0.28; P = 0.45; 3 trials, 249 participants, low quality of evidence). Seven
      trials (692 participants) evaluated fatigue. There is moderate quality of
      evidence that exercise improves fatigue (SMD 0.24; 95% CI 0.08 to 0.40; P =
      0.003).Eight studies evaluated various aspects of physical performance (e.g.
      aerobic capacity, cardiovascular fitness), but none of them could be pooled in a
      meta-analysis. In seven trials there is a tendency or statistically significant
      effect favouring the exercise group (very low quality of evidence).Three trials
      (266 participants) investigated serious adverse events (SAEs) (e.g. bleeding,
      fever, pneumonia, deep vein thrombosis, and infection), and one trial (122
      participants) assessed adverse events (AEs). There is no evidence for a
      difference between arms in terms of SAEs (RR 1.44; 95% CI 0.96 to 2.18; P = 0.06)
      or AEs (RR 7.23; 95% CI 0.38 to 137.05; P = 0.19); both findings are based on low
      quality of evidence. AUTHORS' CONCLUSIONS: There is no evidence for differences
      in mortality between the exercise and control groups. Physical exercise added to
      standard care can improve quality of life, especially physical functioning,
      depression and fatigue. Currently, there is inconclusive evidence regarding
      anxiety, physical performance, serious adverse events and adverse events.We need
      further trials with more participants and longer follow-up periods to evaluate
      the effects of exercise intervention for people suffering from haematological
      malignancies. Furthermore, we need trials with overall survival as the primary
      outcome to determine whether the suggested benefits will translate into a
      survival advantage. To enhance comparability of study data, development and
      implementation of core sets of measuring devices would be helpful.

PMID- 25386667
TI  - N-cadherin, beta-catenin and connexin 43 expression in astrocytic tumours of
      various grades.
AB  - INTRODUCTION: Astrocytic tumors are the most common primary brain tumors, but
      little is known about their etiology and prognostic factors. N-cadherin and beta
      catenin are adhesive proteins, and are often overexpressed in many types of
      cancers, including breast or colorectal cancer, resulting in better prognosis.
      Connexin 43 is a gap junction protein involved in cell-cell signaling pathway
      taking part in the process of carcinogenesis. The aim of the study was to
      evaluate N-cadherin, beta-catenin and connexin 43 expression in astrocytic tumors
      of various grades. MATERIALS AND METHODS: We examined 131 cases of astrocytic
      tumors, including 26 cases of diffuse astrocytoma (group I), 44 anaplasic
      astrocytomas (group II) and 61 glioblastoma cases (group III)--primary and
      secondary. To evaluate N-cadherin, beta-catenin and connexin 43 expression, we
      used immunohistochemical reaction with specific antibodies (Santa Cruz
      Biotechnology). The obtained results were correlated with clinical and
      morphological features. RESULTS: Beta-catenin expression was observed in 69.3% of
      diffuse astrocytomas, 75% of anaplastic astrocytomas, and 82% of glioblastoma
      cases. N-cadherin expression was observed in 92.3% of diffuse astrocytomas, 90.1%
      of anaplastic astyrocytomas, and in all glioblastoma cases. Connexin 43 was
      observed in 76.9% of diffuse astrocytomas, and in all cases of anaplastic
      astrocytomas and glioblastomas. Beta-catenin expression was significant within
      the nucleus of neoplastic cells in groups I and II. In group III, staining was
      observed only in the cellular membranes. N-cadherin and connexin 43 expression
      was observed only in the cells' membranes. In glioblastomas, both primary and
      secondary, all protein expression was significant within the cells surrounding
      the necroses and blood vessels and weak or absent in the tumor's margins.
      CONCLUSION: Our study shows that beta-catenin nuclear expression in group of
      diffuse astrocytomas and anaplastic astrocytomas is evidence for transcriptional
      function of beta-catenin in those groups. Strong N-cadherin and connexin 43
      expression in those groups may be evidence for their role in tumor formation and
      progression. However, in glioblastomas a very important role of all examined
      proteins is generating intracellular connections to facilitate the escape of
      tumor cells from the effects of hypoxia or their accumulation around the blood
      vessels rather than tumor invasion into the brain parenchyma.

PMID- 25386668
TI  - Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical
      parameters in chronic fatigue syndrome?
AB  - Chronic fatigue syndrome (CFS) is a chronic and extremely debilitating illness
      characterized by prolonged fatigue and multiple symptoms with unknown cause,
      diagnostic test, or universally effective treatment. Inflammation, oxidative
      stress, mitochondrial dysfunction, and CoQ10 deficiency have been well documented
      in CFS. We conducted an 8-week, randomized, double-blind placebo-controlled trial
      to evaluate the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day)
      supplementation on fatigue and biochemical parameters in 73 Spanish CFS patients.
      This study was registered in ClinicalTrials.gov (NCT02063126). A significant
      improvement of fatigue showing a reduction in fatigue impact scale total score
      (p<0.05) was reported in treated group versus placebo. In addition, a recovery of
      the biochemical parameters was also reported. NAD+/NADH (p<0.001), CoQ10
      (p<0.05), ATP (p<0.05), and citrate synthase (p<0.05) were significantly higher,
      and lipoperoxides (p<0.05) were significantly lower in blood mononuclear cells of
      the treated group. These observations lead to the hypothesis that the oral CoQ10
      plus NADH supplementation could confer potential therapeutic benefits on fatigue
      and biochemical parameters in CFS. Larger sample trials are warranted to confirm
      these findings.

PMID- 25386669
TI  - Filamentous sludge bulking control by nano zero-valent iron in activated sludge
      treatment systems.
AB  - Sludge bulking causes loss of biomass in the effluent and deterioration of
      effluent water quality. This study explored the use of nano zero-valent iron
      (NZVI with an average particle size of 55 +/- 11 nm) for sludge bulking control.
      In two Modified Ludzack-Ettinger (MLE) activated sludge treatment systems, a
      single dose of NZVI at the final concentration of 100 mg Fe per L in the mixed
      liquor reduced the number of filamentous bacteria Type 021N by 2-3 log units (a
      reduction of 99.9 and 96.7% in MLE tank #1 and #2, respectively). The side effect
      of the use of NZVI depended on sludge bulking conditions and biomass
      concentration. In the system with sludge bulking and significant sludge loss
      (average biomass concentration of 1022 +/- 159 COD mg per L or at the ratio of
      0.098 g Fe per g biomass COD), the use of NZVI increased effluent COD, NH4(+)-N
      and NO2(-)-N concentrations, as also evident with the loss of nitrifying
      populations and nitrifying activities resulting in more than 40 days to have the
      full recovery of the activated sludge system. In contrast, in the system with the
      early stages of bulking and the biomass concentration of 1799 +/- 113 COD mg per
      L (at the ratio of 0.056 g Fe per g biomass COD), the effluent water quality and
      overall bioreactor performance were only slightly affected for a few days. 

PMID- 25386670
TI  - Evaluation of arterial blood flow changes by orbital Doppler in chronic
      obstructive pulmonary disease and asthma.
AB  - PURPOSE: Both chronic obstructive pulmonary disease (COPD) and asthma are
      important causes of morbidity and mortality worldwide. They primarily affect the
      lungs, but they have various extrapulmonary manifestations. The aim of our study
      was to evaluate the hemodynamic changes in orbital vessels of the patients with
      COPD and asthma using color Doppler ultrasonography and compare the results with
      healthy control subjects. METHODS: Thirty-seven patients with COPD, 37 patients
      with asthma, and 41 healthy control subjects were included in this study. All
      patients with COPD were in moderate to severe group according to GOLD (Global
      Initiative for Chronic Obstructive Lung Disease), and similarly, all patients
      with asthma were in moderate to severe persistent group according to GINA (Global
      Initiative for Asthma) 2006 guidelines. End-tidal carbon dioxide, peripheral
      oxygen saturation, pulse rate, and respiratory rate were measured by using pulse
      oximeter in all patients. Measurements were performed in only 1 randomly selected
      eye of each participant. The peak systolic velocity, end diastolic velocity, and
      resistance index were measured in the central retinal artery, temporal posterior
      ciliary artery, and nasal posterior ciliary artery using the color Doppler
      ultrasonography technique. RESULTS: The peak systolic velocity, end diastolic
      velocity, and resistance index values of temporal posterior ciliary artery and
      nasal posterior ciliary artery were significantly higher in COPD and asthma than
      in the control subjects. There was no difference between asthma and COPD.
      CONCLUSIONS: We concluded that retrobulbar hemodynamics change in COPD and asthma
      is showing 1 of the systemic effects in these diseases.

PMID- 25386671
TI  - Interrelationships among cortisol, 17-hydroxyprogesterone, and androstenendione
      exposures in the management of children with congenital adrenal hyperplasia.
AB  - Hydrocortisone is the standard replacement therapy for children with congenital
      adrenal hyperplasia (CAH). Relationships between cortisol exposures and
      pharmacodynamic responses of 17-hydroxyprogesterone and androstenedione exposures
      have not been systematically evaluated. OBJECTIVES: (1) Assess individual oral
      hydrocortisone pharmacokinetics; (2) relate the observed cortisol exposure in
      each subject to the observed exposures of 17-hydroxyprogesterone and
      androstenedione; (3) determine potential individualized treatment regimens based
      on each subject's pharmacokinetic and pharmacodynamic parameters. METHODS: Thirty
      four patients (18 boys, 16 girls, aged 1.4 to 18.1 years) with CAH underwent 6
      hour pharmacokinetic studies. Results were analyzed by noncompartmental methods
      to obtain the area under the curve (AUC) for cortisol, 17-hydroxyprogesterone,
      and androstenedione; maximum concentration and time-to-maximum concentration for
      cortisol; and minimum and time-to-minimum concentration for 17
      hydroxyprogesterone and androstenedione. RESULTS: Mean (SD) cortisol half-life
      and Cmax were 1.01 (0.20) hours and 24.4 (5.4) MUg/dL, respectively. The AUCs for
      cortisol, 17-hydroxyprogesterone and androstenedione were 40.8 (14.5) MUg
      hour/dL, 29,490 (23,539) ng hour/dL, and 680 (795) ng hour/dL, respectively. No
      significant relationships existed between cortisol AUCs and the AUCs of either 17
      hydroxyprogesterone (P=0.32) or androstenedione (P=0.99); nor were there
      differences between the change-from-baseline concentrations for cortisol with
      either 17-hydroxyprogesterone (P=0.80) or androstenedione (P=0.40). Cortisol
      simulations indicated that although four daily doses decreased 24-hour
      hypercortisolemia and hypocortisolemia, substantial periods of each remained.
      CONCLUSIONS: Concentration profiles of cortisol, 17-hydroxyprogesterone, and
      androstenedione are highly variable in children with CAH, and knowledge of them
      can assist in personalizing the therapy of CAH patients. Hydrocortisone's rapid
      half-life and the lack of a sustained-released product make it difficult to
      closely approximate normal circadian profiles.

PMID- 25386672
TI  - Amphiphilic layer-by-layer assembly overcoming solvent polarity between aqueous
      and nonpolar media.
AB  - We introduce a general and versatile methodology that allows a facile
      incorporation of the functional components with completely different chemistry of
      hydrophilic/hydrophobic properties within nanocomposite films, and furthermore
      combine a number of the distinctive advantages of traditional electrostatic layer
      by-layer (LbL) assembly in aqueous media and covalent LbL assembly in nonpolar
      media. Our approach, amphiphilic LbL assembly, is based on the high affinity
      between sulfonic (or phosphonic) acid-functionalized materials in aqueous media
      and hydrophobic metal oxide (or metal) NPs stabilized by oleic acid (OA) in
      nonpolar solvent. For demonstrating the effectiveness of our approach, we show
      that amphiphilic LbL assembly can be easily applied to the preparation of
      functional colloid materials allowing the reversible phase transfer between
      aqueous and nonpolar media, and supercapacitor electrodes with high volumetric
      capacitance (280 F.cm(-3) at 10 mV.s(-1)) using reduced graphene oxide with
      sulfonic acid moieties and well-defined OA-Fe3O4 NPs. 

PMID- 25386673
TI  - Antagonism and synergy of single chain sphingolipids sphingosine and sphingosine
      1-phosphate toward lipid bilayer properties. Consequences for their role as cell
      fate regulators.
AB  - A recurring question in membrane biological chemistry is whether bioactive
      signaling lipids act only as second messenger ligands or also through an effect
      on bilayer physical properties. Sphingosine (Sph) and sphingosine-1-phosphate
      (S1P) are single-chained charged sphingolipids that have antagonistic functions
      in the "sphingolipid rheostat" which determines cell fate. Sph and S1P
      respectively promote apoptosis and cell growth. In the present study, potential
      effects of these bioactive lipids on physicochemical properties of the lipid
      bilayer of cell membranes were evaluated. We have investigated the effect of both
      sphingolipids, incorporated separately or, for the first time, together, in large
      or giant phosphadidylcholine (PC) unilamellar vesicles. Three bilayer properties
      were examined: membrane surface charge, lipid packing, and formation of membrane
      microdomains. Sph and S1P appear to have distinct, when not inverse, effects on
      all three properties. Besides, when both sphingolipids are mixed together, their
      effects on lipid packing are synergistic, whereas their effects on microdomain
      formation and zeta-potential are mostly antagonistic. These results are
      interpreted as arising from different electrostatic interactions between lipid
      headgroups. In particular, Sph and S1P may interact together electrostatically
      and form a complex. These mostly inverse and opposing effects of both single
      chain phospholipids on membrane physical properties might be involved in their
      antagonistic role in regulating cell fate. Particularly, the mutual interaction
      between Sph and S1P as a complex might be able to sequester both molecules in a
      biologically inactive form and therefore to promote a mutual regulation of their
      biological activities, depending on their ratio, consistent with the sphingolipid
      rheostat. 

PMID- 25386674
TI  - Chloroform-assisted phenol extraction improving proteome profiling of maize
      embryos through selective depletion of high-abundance storage proteins.
AB  - The presence of abundant storage proteins in plant embryos greatly impedes seed
      proteomics analysis. Vicilin (or globulin-1) is the most abundant storage protein
      in maize embryo. There is a need to deplete the vicilins from maize embryo
      extracts for enhanced proteomics analysis. We here reported a chloroform-assisted
      phenol extraction (CAPE) method for vicilin depletion. By CAPE, maize embryo
      proteins were first extracted in an aqueous buffer, denatured by chloroform and
      then subjected to phenol extraction. We found that CAPE can effectively deplete
      the vicilins from maize embryo extract, allowing the detection of low-abundance
      proteins that were masked by vicilins in 2-DE gel. The novelty of CAPE is that it
      selectively depletes abundant storage proteins from embryo extracts of both
      monocot (maize) and dicot (soybean and pea) seeds, whereas other embryo proteins
      were not depleted. CAPE can significantly improve proteome profiling of embryos
      and extends the application of chloroform and phenol extraction in plant
      proteomics. In addition, the rationale behind CAPE depletion of abundant storage
      proteins was explored. 

PMID- 25386675
TI  - Experimental food restriction reveals individual differences in corticosterone
      reaction norms with no oxidative costs.
AB  - Highly plastic endocrine traits are thought to play a central role in allowing
      organisms to respond rapidly to environmental change. Yet, not all individuals
      display the same degree of plasticity in these traits, and the costs of this
      individual variation in plasticity are unknown. We studied individual differences
      in corticosterone levels under varying conditions to test whether there are
      consistent individual differences in (1) baseline corticosterone levels; (2)
      plasticity in the hormonal response to an ecologically relevant stressor (food
      restriction); and (3) whether individual differences in plasticity are related to
      fitness costs, as estimated by oxidative stress levels. We took 25 wild-caught
      house sparrows into captivity and assigned them to repeated food restricted and
      control treatments (60% and 110% of their daily food intake), such that each
      individual experienced both food restricted and control diets twice. We found
      significant individual variation in baseline corticosterone levels and stress
      responsiveness, even after controlling for changes in body mass. However, these
      individual differences in hormonal responsiveness were not related to measures of
      oxidative stress. These results have implications for how corticosterone levels
      may evolve in natural populations and raise questions about what we can conclude
      from phenotypic correlations between hormone levels and fitness measures. 

PMID- 25386676
TI  - Psychiatric comorbidity and its impact on mortality in patients who attempted
      suicide by paraquat poisoning during 2000-2010.
AB  - BACKGROUND: Paraquat poisoning is a lethal method of suicide used around the
      world. Although restricting its accessibility had been widely discussed, the
      underlying psychopathological mechanism of paraquat self-poisoning and its
      association with mortality have not yet been explicitly evaluated. METHODS: We
      included all patients admitted to a tertiary general hospital in Taiwan between
      2000 and 2010 following a suicide attempt by paraquat self-administration.
      Diagnoses were made upon psychiatric consultation based on the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The
      risk of mortality was calculated by logistic regression with various psychiatric
      or medical covariates. RESULTS: The consultation-liaison psychiatry team assessed
      157 patients who attempted suicide by paraquat poisoning. Mood disorders (54.0%),
      including dysthymic (26.7%) and major depressive disorders (24.7%), were the most
      common psychiatric diagnoses among the self-poisoning patients. Among those who
      attempted suicide, 87 patients (58.0%) died and dysthymic disorder (OR = 5.58,
      95% CI: 1.13-27.69; p < 0.05) significantly increased the mortality risk after
      adjustment for relevant medical variables, including age, gender, severity index
      of paraquat poisoning (SIPP), and risk for respiratory failure. CONCLUSIONS:
      Awareness of comorbid psychiatric illnesses, especially dysthymic disorder, is
      vital in the prevention and treatment of suicide by paraquat poisoning.

PMID- 25386677
TI  - Intravenous S-ketamine does not inhibit alveolar fluid clearance in a septic rat
      model.
AB  - We previously demonstrated that intratracheally administered S-ketamine inhibits
      alveolar fluid clearance (AFC), whereas an intravenous (i.v.) bolus injection had
      no effect. The aim of the present study was to characterize whether continuous
      i.v. infusion of S-ketamine, yielding clinically relevant plasma concentrations,
      inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which
      might favor the appearance of i.v. S-ketamine at the alveolar surface. AFC was
      measured in fluid-instilled rat lungs. S-ketamine was administered i.v. over 6 h
      (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition
      to the instillate (75 ug/ml). ALI was induced by i.v. lipopolysaccharide (LPS; 7
      mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)
      3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat
      alveolar type-II cells were exposed to S-ketamine (75 ug/ml) and/or LPS (1 mg/ml)
      for 6 h, and transepithelial ion transport was measured as short circuit current
      (ISC). AFC was 27+/-5% (mean+/-SD) over 60 min in control rats and was unaffected
      by i.v. S-ketamine. Tracheal S-ketamine reduced AFC to 18+/-9%. In LPS-treated
      rats, AFC decreased to 16+/-6%. This effect was not enhanced by i.v. S-ketamine.
      LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In
      alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride
      inhibitable sodium transport. Continuous administration of i.v. S-ketamine does
      not affect rat AFC even in endotoxin-induced ALI. Tracheal application with
      direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by
      inhibition of amiloride-inhibitable sodium transport.

PMID- 25386678
TI  - Do post discharge phone calls improve care transitions? A cluster-randomized
      trial.
AB  - IMPORTANCE: The transition from hospital to home can expose patients to adverse
      events during the post discharge period. Post discharge care including phone
      calls may provide support for patients returning home but the impact on care
      transitions is unknown. OBJECTIVE: To examine the effect of a 72-hour post
      discharge phone call on the patient's transition of care experience. DESIGN:
      Cluster-randomized control trial. SETTING: Urban, academic medical center.
      PARTICIPANTS: General medical patients age 18 and older discharged home after
      hospitalization. MAIN OUTCOMES AND MEASURES: Primary outcome measure was the Care
      Transition Measure (CTM-3) score, a validated measure of the quality of care
      transitions. Secondary measures included self-reported adherence to medication
      and follow up plans, and 30-day composite of emergency department (ED) visits and
      hospital readmission. RESULTS: 328 patients were included in the study over an 6
      month period. 114 (69%) received a post discharge phone call, and 214 of all
      patients in the study completed the follow outcome survey (65% response rate). A
      small difference in CTM-3 scores was observed between the intervention and
      control groups (1.87 points, 95% CI 0.47-3.27, p = 0.01). Self-reported adherence
      to treatment plans, ED visits, and emergency readmission rates were similar
      between the two groups (odds ratio 0.57, 95% CI 0.13-2.45, 1.20, 95% CI 0.61
      2.37, and 1.18, 95% CI 0.53-2.61, respectively). CONCLUSIONS AND RELEVANCE: A
      single post discharge phone call had a small impact on the quality of care
      transitions and no effect on hospital utilization. Higher intensity post
      discharge support may be required to improve the patient experience upon
      returning home. TRIAL REGISTRATION: ClinicalTrials.gov NCT01580774.

PMID- 25386679
TI  - Partial versus complete fundoplication for the correction of pediatric GERD: a
      systematic review and meta-analysis.
AB  - BACKGROUND: There is no consensus as to what extent of "wrap" is required in a
      fundoplication for correction of gastroesophageal reflux disease (GERD).
      OBJECTIVE: To evaluate if a complete (360 degree) or partial fundoplication gives
      better control of GERD. METHODS: A systematic search of MEDLINE and Scopus
      identified interventional and observational studies of fundoplication in
      children. Screening identified those comparing techniques. The primary outcome
      was recurrence of GERD following surgery. Dysphagia and complications were
      secondary outcomes of interest. Meta-analysis was performed when appropriate.
      Study quality was assessed using the Cochrane Risk of Bias Tool. RESULTS: 2289
      abstracts were screened, yielding 2 randomized controlled trials (RCTs) and 12
      retrospective cohort studies. The RCTs were pooled. There was no difference in
      surgical success between partial and complete fundoplication, OR 1.33
      [0.67,2.66]. In the 12 cohort studies, 3 (25%) used an objective assessment of
      the surgery, one of which showed improved outcomes with complete fundoplication.
      Twenty-five different complications were reported; common were dysphagia and gas
      bloat syndrome. Overall study quality was poor. CONCLUSIONS: The comparison of
      partial fundoplication with complete fundoplication warrants further study. The
      evidence does not demonstrate superiority of one technique. The lack of high
      quality RCTs and the methodological heterogeneity of observational studies limits
      a powerful meta-analysis.

PMID- 25386680
TI  - Bacillus cereus AR156-induced resistance to Colletotrichum acutatum is associated
      with priming of defense responses in loquat fruit.
AB  - The effectiveness of a biocontrol agent Bacillus cereus AR156 for control of
      anthracnose rot caused by Colletotrichum acutatum in harvested loquat fruit and
      the possible mechanisms of its action have been investigated. Treatment of fruit
      with B. cereus AR156 resulted in lower disease incidence and smaller lesion
      diameters compared with that of untreated fruit. The treatment enhanced
      activities of defense-related enzymes including chitinase, beta-1, 3-glucanase,
      phenylalanine ammonia-lyase, peroxidase and polyphenoloxidase, and promoted
      accumulation of H2O2. Total phenolic content and 2,2-diphenyl-1-picrylhydrazyl
      radical scavenging activity were also increased by treatment. Transcripts of
      three defense-related genes were enhanced only in fruit undergoing both B. cereus
      AR156 treatment and C. acutatum inoculation compared with those receiving either
      intervention alone. These results suggest that the disease resistance against C.
      acutatum in loquat fruit is enhanced by B. cereus AR156 and that the induced
      resistance is associated with induction and priming of defense responses in the
      fruit. 

PMID- 25386681
TI  - Should the Equilibrium Point Hypothesis (EPH) be Considered a Scientific Theory?
AB  - The purpose of this commentary is to discuss factors that limit consideration of
      the equilibrium point hypothesis as a scientific theory. The EPH describes
      control of motor neuron threshold through the variable lambda, which corresponds
      to a unique referent configuration for a muscle, joint, or combination of joints.
      One of the most compelling features of the equilibrium point hypothesis is the
      integration of posture and movement control into a single mechanism. While the
      essential core of the hypothesis is based upon spinal circuitry interacting with
      peripheral mechanics, the proponents have extended the theory to include the
      higher-level processes that generate lambda, and in doing so, imposed an
      injunction against the supraspinal nervous system modeling, computing, or
      predicting dynamics. This limitation contradicts evidence that humans take
      account of body and environmental dynamics in motor selection, motor control, and
      motor adaptation processes. A number of unresolved limitations to the EPH have
      been debated in the literature for many years, including whether muscle
      resistance to displacement, measured during movement, is adequate to support this
      form of control, violations in equifinality predictions, spinal circuits that
      alter the proposed invariant characteristic for muscles, and limitations in the
      description of how the complexity of spinal circuitry might be integrated to
      yield a unique and stable equilibrium position for a given motor neuron
      threshold. In addition, an important empirical limitation of EPH is the
      measurement of the invariant characteristic, which needs to be done under a
      constant central state. While there is no question that the EPH is an elegant and
      generative hypothesis for motor control research, the claim that this hypothesis
      has reached the status of a scientific theory is premature. 

PMID- 25386683
TI  - Benzene absorption in a protuberant-grid-type zinc(II)-organic framework
      triggered by the migration of guest water molecules.
AB  - The 2D protuberant-grid-type Zn(II)-organic framework consists of unusual racemic
      interdigitated bilayers and comprises a 3D intersecting channel system. The
      framework is thermally stable and the channels contain multiple water aggregates.
      Accompanying the migration of guest water molecules, only the specific channels
      in the bilayers along the b axis can easily and efficiently absorb guest benzene
      molecules in a regular manner.

PMID- 25386682
TI  - Functional vascular changes of the kidney during pregnancy in animals: a
      systematic review and meta-analysis.
AB  - Renal vascular responses to pregnancy have frequently been studied, by
      investigating renal vascular resistance (RVR), renal flow, glomerular filtration
      rate (GFR), and renal artery responses to stimuli. Nonetheless, several questions
      remain: 1. Which vasodilator pathways are activated and to what extent do they
      affect RVR, renal flow and GFR across species, strains and gestational ages, 2.
      Are these changes dependent on renal artery adaptation, 3. At which cellular
      level does pregnancy affect the involved pathways? In an attempt to answer the
      questions raised, we performed a systematic review and meta-analysis on animal
      data. We included 37 studies (116 responses). At mid-gestation, RVR and GFR
      change to a similar degree across species and strains, accompanied by variable
      change in renal flow. At least in rats, changes depend on NO activation. At late
      gestation, changes in RVR, renal flow and GFR vary between species and strains.
      In rats, these changes are effectuated by sympathetic stimulation. Overall, renal
      artery responsiveness to stimuli is unaffected by pregnancy, except for Sprague
      Dawley rats in which pregnancy enhances renal artery vascular compliance and
      reduces renal artery myogenic reactivity. Our meta-analysis shows that: 1.
      Pregnancy changes RVR, renal flow and GFR dependent on NO-activation and
      sympathetic de-activation, but adjustments are different among species, strains
      and gestational ages; 2. These changes do not depend on adaptation of renal
      artery responsiveness; 3. It remains unknown at which cellular level pregnancy
      affects the pathways. Our meta-analysis suggests that renal changes during
      pregnancy in animals are qualitatively similar, even in comparison to humans, but
      quantitatively different. 

PMID- 25386684
TI  - Reply to the letter by Nagai M. et al.

PMID- 25386685
TI  - Hypoxic conditioned medium from rat cerebral cortical cells enhances the
      proliferation and differentiation of neural stem cells mainly through PI3-K/Akt
      pathways.
AB  - PURPOSE: To investigate the effects of hypoxic conditioned media from rat
      cerebral cortical cells on the proliferation and differentiation of neural stem
      cells (NSCs) in vitro, and to study the roles of PI3-K/Akt and JNK signal
      transduction pathways in these processes. METHODS: Cerebral cortical cells from
      neonatal Sprague-Dawley rat were cultured under hypoxic and normoxic conditions;
      the supernatant was collected and named 'hypoxic conditioned medium' (HCM) and
      'normoxic conditioned medium' (NCM), respectively. We detected the protein levels
      (by ELISA) of VEGF and BDNF in the conditioned media and mRNA levels (by RT-PCR)
      in cerebral cortical cells. The proliferation (number and size of neurospheres)
      and differentiation (proportion of neurons and astrocytes over total cells) of
      NSCs was assessed. LY294002 and SP600125, inhibitors of PI3-K/Akt and JNK,
      respectively, were applied, and the phosphorylation levels of PI3-K, Akt and JNK
      were measured by western blot. RESULTS: The protein levels and mRNA expressions
      of VEGF and BDNF in 4% HCM and 1% HCM were both higher than that of those in NCM.
      The efficiency and speed of NSCs proliferation was enhanced in 4% HCM compared
      with 1% HCM. The highest percentage of neurons and lowest percentage of
      astrocytes was found in 4% HCM. However, the enhancement of NSCs proliferation
      and differentiation into neurons accelerated by 4% HCM was inhibited by LY294002
      and SP600125, with LY294002 having a stronger inhibitory effect. The increased
      phosphorylation levels of PI3-K, Akt and JNK in 4% HCM were blocked by LY294002
      and SP600125. CONCLUSIONS: 4%HCM could promote NSCs proliferation and
      differentiation into high percentage of neurons, these processes may be mainly
      through PI3-K/Akt pathways.

PMID- 25386686
TI  - Inhibition of GADD34, the stress-inducible regulatory subunit of the endoplasmic
      reticulum stress response, does not enhance functional recovery after spinal cord
      injury.
AB  - Activation of the endoplasmic reticulum stress response (ERSR) is a hallmark of
      various pathological diseases and/or traumatic injuries. Restoration of ER
      homeostasis can contribute to improvement in the functional outcome of these
      diseases. Using genetic and pharmacological inhibition of the PERK-CHOP arm of
      the ERSR, we recently demonstrated improvements in hindlimb locomotion after
      spinal cord injury (SCI) and implicated oligodendrocyte survival as a potential
      mechanism. Here, we investigated the contribution of stress-inducible
      PPP1R15A/GADD34, an ERSR signaling effector downstream of CHOP that
      dephosphorylates eIF2alpha, in the pathogenesis of SCI. We show that although
      genetic ablation of GADD34 protects oligodendrocyte precursor cells (OPCs)
      against ER stress-mediated cell death in vitro and results in differential ERSR
      attenuation in vivo after SCI, there is no improvement in hindlimb locomotor
      function. Guanabenz, a FDA approved antihypertensive drug, was recently shown to
      reduce the burden of misfolded proteins in the ER by directly targeting GADD34.
      Guanabenz protected OPCs from ER stress-mediated cell death in vitro and
      attenuated the ERSR in vivo after SCI. However, guanabenz administration failed
      to rescue the locomotor deficits after SCI. These data suggest that deletion of
      GADD34 alone is not sufficient to improve functional recovery after SCI. 

PMID- 25386687
TI  - A novel association of biventricular cardiac noncompaction and diabetic
      embryopathy: case report and review of the literature.
AB  - Diabetic embryopathy refers to a constellation of congenital malformations
      arising in the setting of poorly controlled maternal diabetes mellitus. Cardiac
      abnormalities are the most frequently observed findings, with a 5-fold risk over
      normal pregnancies. Although a diverse spectrum of cardiac defects has been
      documented, cardiac noncompaction morphology has not been associated with this
      syndrome. In this report, we describe a novel case of biventricular cardiac
      noncompaction in a neonate of a diabetic mother. The patient was a late preterm
      female with right anotia, caudal dysgenesis, multiple cardiac septal and aortic
      arch defects, and biventricular cardiac noncompaction. Examination of both
      ventricles demonstrated spongy myocardium with increased myocardial trabeculation
      greater than 50% left ventricular thickness and greater than 75% right
      ventricular thickness, with hypoplasia of the bilateral papillary muscles,
      consistent with noncompaction morphology. Review of the literature highlights the
      importance of gene expression and epigenomic regulation in cardiac embryogenesis.

PMID- 25386688
TI  - Transcriptome of the invasive brown marmorated stink bug, Halyomorpha halys
      (Stal) (Heteroptera: Pentatomidae).
AB  - Halyomorpha halys (Stal) (Heteroptera: Pentatomidae), the brown marmorated stink
      bug, is an invasive agricultural and nuisance pest rapidly expanding its
      incidence in North America. This voracious pest poses a significant threat to
      rural and urban agriculture, especially to specialty crops such as apples, grapes
      and ornamentals, as well as staple crops including soybean and corn. The object
      of this study was to generate transcript sequence resources for H. halys. RNA-seq
      libraries derived from distinct developmental stages and sexes were sequenced and
      assembled into 248,569 putatively unique transcripts (PUTs). PUTs were segmented
      into three disjoint tiers of varying reliability, with 4,794 classified as gold
      tier (highest quality), 16,878 as silver, and 14,357 as bronze. The gold-tier
      PUTs associated with 2,580 distinct non-redundant protein sequences from the NCBI
      NR database--1,785 of these (69%) mapped to annotated UniProtKB database
      proteins, from which 1,273 unique Pfam families and 459 unique Molecular Function
      GO terms were encountered. Of the silver tier's 6,527 PUTs associated with unique
      proteins, 4,193 mapped to UniProtKB (64%), from which 1,941 and 640 unique Pfam
      and Molecular Function GO terms were extracted. H. halys PUTs related to
      important life processes like immunity, endocrinology, reproduction, development,
      behavior, neurotransmission, neurotoxicity, olfaction, and small RNA pathways
      were validated through quantitative Real-Time PCR (qRT-PCR) for differential
      expression during distinct life stages (eggs, 2nd instar nymphs, 4th instar
      nymphs, female adults, male adults). PUTs similar to hypothetical proteins
      identified in symbiont microbes, including Pantoea and Nosema species, were more
      abundantly expressed in adults versus nymphs. These comprehensive H. halys
      transcriptomic resources can be utilized to aid development of novel control
      methodologies to disrupt life processes; to conduct reverse genetic screens to
      determine host gene function; and to design environmentally unobtrusive means to
      control host populations or target specific H. halys life stages, such as
      molecular biopesticides.

PMID- 25386690
TI  - Mutational analysis of angiogenin gene in Parkinson's disease.
AB  - Mutations in the angiogenic factor, angiogenin (ANG), have been identified in
      patients with both familial and sporadic amyotrophic lateral sclerosis (ALS) and
      are thought to have a neuroprotective function. Parkinsonism has been noted in
      kindreds with ANG mutations and variants in the ANG gene have been found to
      associate with PD in two Caucasian populations. We therefore hypothesized that
      mutations in ANG may also contribute to idiopathic Parkinson's disease (PD). We
      sequenced ANG gene in a total of 1498 participants comprising 750 PD patients and
      748 age/gender matched controls from Taiwan. We identified one novel synonymous
      substitution, c.C100T (p.L10L), in a single heterozygous state in one PD patient,
      which was not observed in controls. The clinical phenotypes and [99mTc]-TORDAT
      SPECT images of the p.L10L carrier were similar to that seen in idiopathic PD. In
      addition, we also identified one common variant, c.T330G (p.G110G, rs11701),
      which was previously reported to associate with PD risk in Caucasians. However,
      the frequency of TG/GG genotype was comparable between PD cases and controls
      (odds ratio: 0.85, 95% confidence interval: 0.29-2.55, P = 0.78). Our results did
      not support that ANG rs11701 variant is a genetic risk factor for PD in our
      population. We conclude that mutations in ANG are not a common cause for
      idiopathic PD. 

PMID- 25386691
TI  - Variation in seed fatty acid composition and sequence divergence in the FAD2 gene
      coding region between wild and cultivated sesame.
AB  - Sesame germplasm harbors genetic diversity which can be useful for sesame
      improvement in breeding programs. Seven accessions with different levels of oleic
      acid were selected from the entire USDA sesame germplasm collection (1232
      accessions) and planted for morphological observation and re-examination of fatty
      acid composition. The coding region of the FAD2 gene for fatty acid desaturase
      (FAD) in these accessions was also sequenced. Cultivated sesame accessions
      flowered and matured earlier than the wild species. The cultivated sesame seeds
      contained a significantly higher percentage of oleic acid (40.4%) than the seeds
      of the wild species (26.1%). Nucleotide polymorphisms were identified in the FAD2
      gene coding region between wild and cultivated species. Some nucleotide
      polymorphisms led to amino acid changes, one of which was located in the enzyme
      active site and may contribute to the altered fatty acid composition. Based on
      the morphology observation, chemical analysis, and sequence analysis, it was
      determined that two accessions were misnamed and need to be reclassified. The
      results obtained from this study are useful for sesame improvement in molecular
      breeding programs. 

PMID- 25386692
TI  - Sleep and the Housing and Neighborhood Environment of Urban Latino Adults Living
      in Low-Income Housing: The AHOME Study.
AB  - Sleep is implicated in the risk of many chronic diseases; however, little is
      known about the living conditions that influence sleep. In this study of 371 low
      income Latino residents, household crowding was associated with reduced odds of
      long sleep duration relative to average and short sleep duration. Neighborhood
      disorder and perceived building problems were associated with more sleep
      disturbances and poor sleep quality. Building problems were associated with
      prolonged sleep latency. There was a significant cumulative effect of adverse
      housing and neighborhood conditions on sleep outcomes. These results show that
      adverse conditions of both the housing and neighborhood environments are
      associated with poor sleep outcomes. 

PMID- 25386694
TI  - e-Learning versus lecture-based courses in ECG interpretation for undergraduate
      medical students: a randomized noninferiority study.
AB  - OBJECTIVE: An ECG is pivotal for the diagnosis of coronary heart disease.
      Previous studies have reported deficiencies in ECG interpretation skills that
      have been responsible for misdiagnosis. However, the optimal way to acquire ECG
      interpretation skills is still under discussion. Thus, our objective was to
      compare the effectiveness of e-learning and lecture-based courses for learning
      ECG interpretation skills in a large randomized study. PARTICIPANTS AND METHODS:
      We conducted a prospective, randomized, controlled, noninferiority study.
      Participants were recruited from among fifth-year medical students and were
      assigned to the e-learning group or the lecture-based group using a computer
      generated random allocation sequence. The e-learning and lecture-based groups
      were compared on a score of effectiveness, comparing the 95% unilateral
      confidence interval (95% UCI) of the score of effectiveness with the mean
      effectiveness in the lecture-based group, adjusted for a noninferiority margin.
      RESULTS: Ninety-eight students were enrolled. As compared with the lecture-based
      course, e-learning was noninferior with regard to the postcourse test score
      (15.1; 95% UCI 14.2; +infinity), which can be compared with 12.5 [the mean
      effectiveness in the lecture-based group (15.0) minus the noninferiority margin
      (2.5)]. Furthermore, there was a significant increase in the test score points in
      both the e-learning and lecture-based groups during the study period (both
      P<0.0001). CONCLUSION: Our randomized study showed that the e-learning course is
      an effective tool for the acquisition of ECG interpretation skills by medical
      students. These preliminary results should be confirmed with further multicenter
      studies before the implementation of e-learning courses for learning ECG
      interpretation skills during medical school.

PMID- 25386693
TI  - Polyunsaturated fatty acid composition of maternal diet and erythrocyte
      phospholipid status in Chilean pregnant women.
AB  - Chilean diets are characterized by a low supply of n-3 polyunsaturated fatty
      acids (n-3 PUFA), which are critical nutrients during pregnancy and lactation,
      because of their role in brain and visual development. DHA is the most relevant n
      3 PUFA in this period. We evaluated the dietary n-3 PUFA intake and erythrocyte
      phospholipids n-3 PUFA in Chilean pregnant women. Eighty healthy pregnant women
      (20-36 years old) in the 3rd-6th month of pregnancy were included in the study.
      Dietary assessment was done applying a food frequency questionnaire, and data
      were analyzed through the Food Processor SQL(r) software. Fatty acids of
      erythrocyte phospholipids were assessed by gas-liquid chromatography. Diet
      composition was high in saturated fat, low in mono- and PUFA, high in n-6 PUFA
      (linoleic acid) and low in n-3 PUFA (alpha-linolenic acid and DHA), with
      imbalance in the n-6/n-3 PUFA ratio. Similar results were observed for fatty
      acids from erythrocyte phospholipids. The sample of Chilean pregnant women showed
      high consumption of saturated fat and low consumption of n-3 PUFA, which is
      reflected in the low DHA content of erythrocyte phospholipids. Imbalance between
      n-6/n-3 PUFA could negatively affect fetal development. New strategies are
      necessary to improve n-3 PUFA intake throughout pregnancy and breast feeding
      periods. Furthermore, it is necessary to develop dietary interventions to improve
      the quality of consumed foods with particular emphasis on n-3 PUFA. 

PMID- 25386695
TI  - Localized hypothermia aggravates bleeding in the collagenase model of
      intracerebral hemorrhage.
AB  - Animal studies testing whether therapeutic hypothermia is neuroprotective after
      intracerebral hemorrhage (ICH) have been inconclusive. In rodents, ICH is often
      produced in the striatum by infusing collagenase, which causes prolonged
      hemorrhaging from multiple vessels. Our previous data shows that this bleeding
      (hematoma) is worsened by systemic hypothermia given soon after collagenase
      infusion. In this study we hypothesized that localized brain hypothermia would
      also aggravate bleeding in this model (0.2 U of collagenase in 1.2 MUL of
      saline). We also evaluated cooling after intrastriatal thrombin infusion (1 U in
      30 MUL of saline)-a simplified model of ICH thought to cause bleeding. Focal
      hypothermia was achieved by flushing cold water through an implanted cooling
      device attached to the skull underneath the temporalis muscle of adult rats.
      Previous work and data at this time shows this method cools the striatum to ~33
      degrees C, whereas the body remains normothermic. In comparison to normothermic
      groups, cooling significantly worsened bleeding when instituted at 6 hours (~94
      vs. 42 MUL, p=0.018) and 12 hours (79 vs. 61 MUL, p=0.042) post-ICH (24-hour
      survival), but not after a 24-hour delay (36-hour survival). Rats were cooled
      until euthanasia when hematoma size was determined by a hemoglobin-based
      spectrophotometry assay. Cooling did not influence cerebral blood volume after
      just saline or thrombin infusion. The latter is explained by the fact that
      thrombin did not cause bleeding beyond that caused by saline infusion. In
      summary, local hypothermia significantly aggravates bleeding many hours after
      collagenase infusion suggesting that bleeding may have confounded earlier studies
      with hypothermia. Furthermore, these findings serve as a cautionary note on using
      cooling even many hours after cerebral bleeding.

PMID- 25386696
TI  - Applications of low altitude remote sensing in agriculture upon farmers' requests
      -a case study in northeastern Ontario, Canada.
AB  - With the growth of the low altitude remote sensing (LARS) industry in recent
      years, their practical application in precision agriculture seems all the more
      possible. However, only a few scientists have reported using LARS to monitor crop
      conditions. Moreover, there have been concerns regarding the feasibility of such
      systems for producers given the issues related to the post-processing of images,
      technical expertise, and timely delivery of information. The purpose of this
      study is to showcase actual requests by farmers to monitor crop conditions in
      their fields using an unmanned aerial vehicle (UAV). Working in collaboration
      with farmers in northeastern Ontario, we use optical and near-infrared imagery to
      monitor fertilizer trials, conduct crop scouting and map field tile drainage. We
      demonstrate that LARS imagery has many practical applications. However, several
      obstacles remain, including the costs associated with both the LARS system and
      the image processing software, the extent of professional training required to
      operate the LARS and to process the imagery, and the influence from local weather
      conditions (e.g. clouds, wind) on image acquisition all need to be considered.
      Consequently, at present a feasible solution for producers might be the use of
      LARS service provided by private consultants or in collaboration with LARS
      scientific research teams. 

PMID- 25386697
TI  - Robot-assisted surgical approach to bladder cancer: a decade of progress!
AB  - Robot-assisted radical cystectomy (RARC) has gained popularity and proven its
      efficacy, safety and reproducibility in the last decade. RARC has resulted in
      less blood loss, enhanced recovery, and shorter hospital stay. RARC has proven to
      have similar or better postoperative morbidity, mortality and equal oncologic,
      outcomes. Limiting factors to the acceptance of this surgical approach have
      included its steep learning curve and the lack of both long-term outcome data.
      This article systematically reviews the literature comparing the outcomes for
      RARC (comparisons with open radical cystectomy when performed at the same
      institution) with a focus on operative, complications, oncologic, functional and
      survival outcomes. 

PMID- 25386698
TI  - Multiparametric classification links tumor microenvironments with tumor cell
      phenotype.
AB  - While it has been established that a number of microenvironment components can
      affect the likelihood of metastasis, the link between microenvironment and tumor
      cell phenotypes is poorly understood. Here we have examined microenvironment
      control over two different tumor cell motility phenotypes required for
      metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in
      mice, we detected two phenotypes of motile tumor cells, different in locomotion
      speed. Only slower tumor cells exhibited protrusions with molecular,
      morphological, and functional characteristics associated with invadopodia. Each
      region in the primary tumor exhibited either fast- or slow-locomotion. To
      understand how the tumor microenvironment controls invadopodium formation and
      tumor cell locomotion, we systematically analyzed components of the
      microenvironment previously associated with cell invasion and migration. No
      single microenvironmental property was able to predict the locations of tumor
      cell phenotypes in the tumor if used in isolation or combined linearly. To solve
      this, we utilized the support vector machine (SVM) algorithm to classify
      phenotypes in a nonlinear fashion. This approach identified conditions that
      promoted either motility phenotype. We then demonstrated that varying one of the
      conditions may change tumor cell behavior only in a context-dependent manner. In
      addition, to establish the link between phenotypes and cell fates, we
      photoconverted and monitored the fate of tumor cells in different
      microenvironments, finding that only tumor cells in the invadopodium-rich
      microenvironments degraded extracellular matrix (ECM) and disseminated. The
      number of invadopodia positively correlated with degradation, while the
      inhibiting metalloproteases eliminated degradation and lung metastasis,
      consistent with a direct link among invadopodia, ECM degradation, and metastasis.
      We have detected and characterized two phenotypes of motile tumor cells in vivo,
      which occurred in spatially distinct microenvironments of primary tumors. We show
      how machine-learning analysis can classify heterogeneous microenvironments in
      vivo to enable prediction of motility phenotypes and tumor cell fate. The ability
      to predict the locations of tumor cell behavior leading to metastasis in breast
      cancer models may lead towards understanding the heterogeneity of response to
      treatment. 

PMID- 25386699
TI  - Assessment of spiritual suffering in the cancer context: A systematic literature
      review.
AB  - OBJECTIVE: An important goal of cancer medicine is relief of patients' suffering.
      In view of the clinical challenges of identifying suffering patients, we sought
      to identify valid instruments for assessing the spiritual suffering of people
      diagnosed with cancer. METHOD: A systematic review of the literature was
      conducted in the Medline, Embase, the Cochrane Library, and PsycINFO databases
      seeking assessment instruments that measure either suffering or one of its
      synonyms or symptoms. The psychometric properties of the identified measures were
      compared. RESULTS: A total of 90 articles were identified that supplied
      information about 58 measures. The constructs examined were: suffering,
      hopelessness/demoralization, hope, meaning, spiritual well-being, quality of life
      where a spiritual/existential dimension was included, distress in the palliative
      care setting and pain, distress or struggle of a spiritual nature. The Pictorial
      Representation of Illness and Self Measure (PRISM) (patient completed) was the
      most promising measure identified for measuring the burden of suffering caused by
      illness due to its ease of use and the inclusion of a subjective component.
      SIGNIFICANCE OF RESULTS: Although the appropriateness of any measure for the
      assessment of spiritual suffering in cancer patients will depend on the context
      in which it is intended to be utilized, the PRISM is promising for measuring the
      burden of suffering due to illness.

PMID- 25386700
TI  - Ag(I) and Tl(I) precursors as transfer agents of a pyrrole-based pincer ligand to
      late transition metals.
AB  - A PNP ligand, PN(pyr)P ((PN(pyr)P)H = 2,5-bis((di-iso
      propylphosphino)methyl)pyrrole), which employs a pyrrole unit as a central
      anionic nitrogen donor, was designed. The corresponding group 10 metal chlorides
      as well as iridium and ruthenium compounds were isolated. In order to conduct
      this work, [(PN(pyr)P)Tl] and [(PN(pyr)P)Ag]2 were synthesized and characterized.
      The thallium and silver species were paramount in the formation of the iridium
      and ruthenium complexes, which could not be isolated using (PN(pyr)P)H or the
      corresponding lithium pyrrolide salt. Interestingly, the solid state molecular
      structure of [(PN(pyr)P)Tl] indicates that the metal center engages in an eta(2)
      intermolecular interaction with the backbone of a neighboring pyrrole molecule
      instead of the expected bonding to the phosphine arms. 

PMID- 25386702
TI  - Attentional Processing of Letter Strings by Children.
AB  - Reading a letter string requires attentional orienting toward the beginning of
      the string (left-dominant orientation), followed by orienting along the string.
      These attentional-orienting processes differ according to the lexicality of the
      letter string: Sequential processes apply when reading nonwords or pseudowords,
      while words can be processed more globally. The aim of this study was to evaluate
      the development of these attentional processes involved in reading. We conducted
      two experiments in 6- (first grade), 7- (second grade), and 9-year-old (fourth
      grade) children, using a procedure that required the detection of a letter
      (Experiment 1) or a nonletter (Experiment 2) target in a string of five
      characters. The target character could occur in the second (left) or fourth
      (right) position in the string. Results showed an advantage for left nonletter
      targets as early as age 6 and of left letter targets as early as age 7. In 6-year
      olds, only good readers detected a left letter target faster than a right letter
      target; others detected a right letter target faster. Thus, dominant orienting
      toward the beginning of the letter string is not fully developed in children
      before the second year of reading. A possibility is that beginning readers have
      difficulties inhibiting an attention-orienting bias toward the right visual field
      in linguistic tasks. The results also showed that the lexicality effect on these
      attentional processes develops gradually until the fourth year of reading. We
      believe that the procedure used in this study will be very valuable for
      evaluating attentional difficulties during reading acquisition. 

PMID- 25386701
TI  - Spatiotemporal characterization of a fibrin clot using quantitative phase
      imaging.
AB  - Studying the dynamics of fibrin clot formation and its morphology is an important
      problem in biology and has significant impact for several scientific and clinical
      applications. We present a label-free technique based on quantitative phase
      imaging to address this problem. Using quantitative phase information, we
      characterized fibrin polymerization in real-time and present a mathematical model
      describing the transition from liquid to gel state. By exploiting the inherent
      optical sectioning capability of our instrument, we measured the three
      dimensional structure of the fibrin clot. From this data, we evaluated the
      fractal nature of the fibrin network and extracted the fractal dimension. Our non
      invasive and speckle-free approach analyzes the clotting process without the need
      for external contrast agents. 

PMID- 25386703
TI  - Influence of an awareness program on Portuguese middle and high school students'
      perceptions of peers with disabilities.
AB  - The ongoing topic of attitudes toward inclusion of students with disabilities in
      Physical Education (PE) classes emphases the role of schools as a primary place
      where attitudes toward disabilities can be changed. The effect of an awareness
      program on students' attitudes toward the inclusion of peers with disabilities in
      PE was examined, as well as variables such as sex, age, previous contact with
      disability, and competitiveness. The participants were 509 students (235 girls,
      274 boys; M age = 13.3 yr., SD = 1.1, range = 11-16), who attended middle and
      high Portuguese schools. The awareness intervention comprised a one-week program
      (2 PE classes, 90 min. and 45 min.). Attitudes were assessed before and after the
      intervention. The awareness program appeared to have a positive influence on
      changing students' attitudes toward inclusion in PE.

PMID- 25386704
TI  - A note on a new study of intelligence in Egypt.
AB  - Three studies of intelligence in Egypt published between 1957 and 1989 and based
      on small samples gave British IQs between 77 and 83. The present paper reports
      the results of a recent study based on a much larger sample in order to examine
      how far the results of the older studies can be replicated. The Coloured
      Progressive Matrices was standardized in Egypt in 2011-2013 on a sample of 11,284
      children aged 5.6 to 10.5 years. The sample obtained a British IQ of 84.2 and
      provides a satisfactory replication of the earlier studies.

PMID- 25386706
TI  - Bayesian analysis of glomerular filtration rate trajectories in kidney transplant
      recipients: a pilot study.
AB  - BACKGROUND: Detailed modeling and analysis of renal (dys)function trajectories
      has not been undertaken in kidney transplant recipients. Although previous
      studies have assumed linear trajectories, this likely represents an
      oversimplification. METHODS: In this study, a Bayesian smoothing technique was
      undertaken to create 10,000 Monte Carlo samples for each of 158 patients over a
      median of 88 months. Specific parameters investigated were the prevalence of
      nonlinear trajectories, periods of nonprogression, and of rapid progression.
      RESULTS: Forty-five (28%) patients displayed high probability (>80%) for a
      nonlinear trajectory. Periods of nonprogression were also common, present in 110
      (70%) patients. A substantial proportion of patients showed deviation from the
      classic paradigm of progressive linear loss of graft function with 137 (87%)
      patients displaying nonlinearity or nonprogression. Only nine (6%) patients
      demonstrated at least one episode of nonprogression after an episode of
      progression, that is, once progression occurred, a subsequent period of
      nonprogression was uncommon. Episodes of nonprogression were less common (P <
      0.001) in patients whose grafts subsequently failed, whereas episodes of rapid
      progression were more common (P = 0.04). CONCLUSION: This study highlights the
      often nonlinear and nonprogressive nature of renal function decline after
      transplantation. Heightened understanding of the factors influencing these
      trajectories should help inform patients and clinicians alike.

PMID- 25386707
TI  - Molecular docking and dynamics simulation study on the influence of Zn2+ on the
      binding modes of aggrecanase with its inhibitors.
AB  - Zinc plays a vital role in structural organization, regulation of function and
      stabilization of the folded protein, which ultimately activates or inactivates
      the binding sites of the protein. Its transition makes a major change in the
      protein and its binding affinity. The ligand binding aggrecanases can be
      influenced by Zn2+ ions; therefore the study focuses on checking the binding mode
      in the presence and absence of zinc using Docking and Molecular dynamics
      simulation. The crystal structure with zinc was considered as wild type (ADAMTS-4
      1Zn2+, ADAMTS-5-1Zn2+) and the crystal structure without zinc was considered as
      the mutant type (ADAMTS-4-0Zn2+, ADAMTS-5-0Zn2+). Mutations were made manually by
      deleting the zinc atom. ADAMTS-4-1Zn2+ had the best Glide score of -12.66
      kcal.mol-1, whereas ADAMTS-4-0Zn2+ had -11.69 kcal.mol-1. ADAMTS-4-1Zn2+ had the
      best glide energy of -72.29 kcal.mol-1, whereas ADAMTS-4-0Zn2+ had-68.44 kcal.mol
      1. ADAMTS-4-1Zn2+ had the best glide e-model of -116.34, whereas ADAMTS-4-0Zn2+
      had -104.264. The RMSD value for ADAMTS-4-1Zn2+ and ADAMTS-4-0Zn2+ was 1.9. These
      results suggested that the absence of zinc decreases the binding affinity of
      ADAMTS-4 with its inhibitor. ADAMTS-5-1Zn2+ had the best Glide score of -8.32
      kcal.mol-1, whereas ADAMTS-5-0Zn2+ had -6.62 kcal.mol-1. ADAMTS-5-1Zn2+ had the
      best glide energy of -70.28 kcal.mol-1, whereas ADAMTS-5-0Zn2+ had -66.02
      kcal.mol-1. ADAMTS-5-1Zn2+ had the best glide e-model of-108.484, whereas ADAMTS
      5-0Zn2+ had -93.81. The RMSD value for ADAMTS-5-1Zn2+ and ADAMTS-5-0Zn2+ was
      0.48A. These results confirmed that the absence of zinc decreased the binding
      affinity of ADAMTS-5 with its inhibitor whereas the presence extended the docking
      energy range and strengthened the binding affinity. Per-residue interaction
      study, MM-GBSA and Molecular Dynamics showed that all the four complexes
      underwent extensive structural changes whereas the complex with zinc was stable
      throughout the simulation period.

PMID- 25386708
TI  - Individual differences in learning a novel discrete motor task.
AB  - Many motor learning studies focus on average performance while it is known from
      everyday life experience that humans differ in their way of learning new motor
      tasks. This study emphasises the importance of recognizing individual differences
      in motor learning. We studied individual tool grasping profiles of individuals
      who learned to pick up objects with a novel tool, a pair of pliers. The pair of
      pliers was attached to the thumb and the index finger so that the tip of the
      thumb and the tip of the index finger were displaced to the beaks of the pair of
      pliers. The grasp component was manipulated by varying the location of the hinge
      of the pair of pliers, which resulted in different relations between beak opening
      and closing and finger opening and closing. The Wider Beak group had the hinge at
      7 cm, the Same Beak group had the hinge at 10 cm (i.e., in the middle), and the
      Smaller Beak group had the hinge at 13 cm from the digits. Each group consisted
      of ten right-handed participants who picked up an object with one of the pairs of
      pliers 200 times on two subsequent days. Hand opening, plateau phase, hand
      closing, grasping time and maximum aperture were analyzed. To characterize
      individual changes over practice time, a log function was fitted on these
      dependent variables and the ratio of improvement was determined. Results showed
      that at the beginning stage of tool use learning the characteristic grasping
      profile consisted of three phases; hand opening, plateau phase and hand closing.
      Over practicing individual participants differed in the number of phases that
      changed, the amount of change in a phase and/or the direction of change.
      Moreover, with different pliers different learning paths were found. The
      importance of recognizing individual differences in motor learning is discussed. 

PMID- 25386710
TI  - Microvascular Dilator Function in Athletes: A Systematic Review and Meta
      analysis.
AB  - PURPOSE: Despite the growing research interest in vascular adaptations to
      exercise training over the last few decades, it remains unclear whether
      microvascular function in healthy subjects can be further improved by regular
      training. Herein, we sought to systematically review the literature and determine
      whether microvascular dilator function is greater in athletes compared to age
      matched healthy untrained subjects. METHODS: We conducted a systematic search of
      MEDLINE, Cochrane, EMBASE, and Web of Science since their inceptions until
      October 2013 for articles evaluating indices of primarily microvascular
      endothelium-dependent or endothelium-independent dilation (MVEDD and MVEID,
      respectively) in athletes. A meta-analysis was performed to determine the
      standardized mean difference (SMD) in MVEDD and MVEID between athletes and age
      matched controls. Subgroup analyses were used to study potential moderating
      factors. RESULTS: Thirty-six studies were selected after systematic review,
      comprising 521 athletes (506 endurance-trained and 15 endurance- and strength
      trained) and 496 age-matched control subjects. After data pooling, athletes
      presented higher MVEDD (31 studies; SMD, 0.47; P < 0.00001) and MVEID (14
      studies; SMD, 0.51; P < 0.00001) compared with the control subjects. Similar
      results were observed in young (younger than 40 yr) and master (older than 55 yr)
      athletes when analyzed separately. CONCLUSION: Both young and master athletes
      present enhanced microvascular function compared with age-matched untrained but
      otherwise healthy subjects. These data provide evidence of a positive association
      between exercise training and microvascular function in the absence of known
      underlying cardiovascular disease.

PMID- 25386711
TI  - Effect of Intravenous Iron on Aerobic Capacity and Iron Metabolism in Elite
      Athletes.
AB  - PURPOSE: Iron-deficient athletes are often treated with long-term, low-dose iron
      therapy. Such treatments may be efficacious in correcting iron deficiency;
      however, the effect on acute and chronic iron metabolism and subsequent endurance
      capacity is less clear. METHODS: Fifteen national and international standard
      runners were identified as iron deficient nonanemic (IDNA) and assigned to either
      an intravenous iron treatment group or placebo group. Participants completed
      three exercise tests to volitional exhaustion, as follows: before treatment,
      within 24 h, and 4 wk after treatment. RESULTS: Serum ferritin, serum iron, and
      transferrin saturation were significantly improved in the iron group after
      intervention and compared with those in placebo (P < 0.05). Hepcidin levels were
      significantly greater before and after exercise after the iron injection (P <
      0.05), and this was independent of changes in interleukin-6. There were no
      differences between groups in red cell indices, total hemoglobin mass, VO2max,
      submaximal blood lactate, running economy, RPE, or time to exhaustion (P > 0.05).
      CONCLUSIONS: A single 500-mg intravenous iron injection is effective for
      improving iron status for at least 4 wk, but this does not lead to improved
      aerobic capacity. This investigation suggests that iron availability supersedes
      inflammation in the regulation of hepcidin in IDNA endurance athletes after acute
      intravascular iron injection treatment.

PMID- 25386712
TI  - Effects of Five Nights under Normobaric Hypoxia on Sleep Quality.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of five nights'
      sleep under normobaric hypoxia on ventilatory acclimatization and sleep quality.
      METHODS: Seven men initially slept for six nights under normoxia and then for
      five nights under normobaric hypoxia equivalent to a 2000-m altitude. Nocturnal
      polysomnograms (PSGs), arterial blood oxygen saturation (SpO2), and respiratory
      events were recorded on the first and fifth nights under both conditions.
      RESULTS: The hypoxic ventilatory response (HVR), hypercapnic ventilatory response
      (HCVR), and resting end-tidal CO2 (resting PETCO2) were measured three times
      during the experimental period. The duration of slow-wave sleep (SWS: stage N3)
      and the whole-night delta (1-3 Hz) power of nonrapid eye movement (NREM) sleep
      EEG decreased on the first night under hypoxia. This hypoxia-induced sleep
      quality deterioration on the first night was accompanied by a lower mean and
      minimum SpO2, a longer time spent with SpO2 below 90% (<90% SpO2 time), and more
      episodes of respiratory disturbance. On the fifth night, the SWS duration and
      whole-night delta power did not differ between the conditions. Although the mean
      SpO2 under hypoxia was still lower than under normoxia, the minimum SpO2
      increased, and the <90% SpO2 time and number of episodes of respiratory
      disturbance decreased during the five nights under hypoxia. The HVR increased and
      resting PETCO2 decreased after five nights under hypoxia. CONCLUSIONS: The
      results suggest that five nights under hypoxia improves the sleep quality. This
      may be derived from improvements of respiratory disturbances, the minimum SpO2,
      and <90% SpO2 time.

PMID- 25386713
TI  - Effects of Creatine and Resistance Training on Bone Health in Postmenopausal
      Women.
AB  - PURPOSE: Our primary purpose was to determine the effect of 12 months of creatine
      (Cr) supplementation during a supervised resistance training program on
      properties of bone in postmenopausal women. METHODS: Participants were randomized
      (double-blind) into two groups: resistance training (3 d.wk) and Cr
      supplementation (0.1 g.kg.d) or resistance training and placebo (Pl). Our primary
      outcome measures were lumbar spine and femoral neck bone mineral density (BMD).
      Secondary outcome measures were total hip and whole-body BMD, bone geometric
      properties at the hip, speed of sound at the distal radius and tibia, whole-body
      lean tissue mass, muscle thickness, and bench press and hack squat strength.
      Forty-seven women (57 (SD, 6) yr; Cr, n = 23; Pl, n = 24) were randomized, with
      33 analyzed after 12 months (Cr, n = 15; Pl, n = 18). RESULTS: Cr attenuated the
      rate of femoral neck BMD loss (-1.2%; absolute change (95% confidence interval), 
      0.01 (-0.025 to 0.005) g.cm) compared with Pl (-3.9%; -0.03 (-0.044 to -0.017)
      g.cm; P < 0.05) and also increased femoral shaft subperiosteal width, a predictor
      of bone bending strength (Cr, 0.04 (-0.09 to 0.16) cm); Pl, -0.12 (-0.23 to 
      0.01) cm; P < 0.05). Cr increased relative bench press strength more than Pl (64%
      vs 34%; P < 0.05). There were no differences between groups for other outcome
      measures. There were no differences between groups for reports of serum liver
      enzyme abnormalities, and creatinine clearance was normal for Cr participants
      throughout the intervention. CONCLUSIONS: Twelve months of Cr supplementation
      during a resistance training program preserves femoral neck BMD and increases
      femoral shaft superiosteal width, a predictor of bone bending strength, in
      postmenopausal women.

PMID- 25386714
TI  - Personality Correlates of Physical Activity in College Women.
AB  - Commonly reported relationships of the broad personality traits of extraversion
      and neuroticism with self-reports of physical activity (PA) have not been
      elaborated within motivational theory that posits how functioning of the
      behavioral inhibition (BIS) and activation (BAS) systems can explain or modify
      the influence of personality on PA. Whether personality predicts physical
      activity when it is measured objectively has not been established. PURPOSE: The
      study was aimed to test direct, indirect, and interactive relations between
      extraversion, neuroticism, BIS and BAS, and PA measured by validated self-report
      and accelerometry. METHODS: Two samples of female undergraduates completed
      personality questionnaires. Sample 2 also completed three PA self-reports and
      wore an accelerometer for 7 d. Factor structure and measurement equivalence of
      personality measures, structural equivalence of relationships between personality
      factors, and multivariate prediction of self-reported and objectively measured PA
      by personality were tested using structural equation modeling. RESULTS:
      Equivalence between samples for personality models was confirmed. Behavioral
      activation system predicted self-reported PA. Neuroticism and BIS predicted
      objectively measured PA. CONCLUSIONS: The relationship between personality and PA
      may differ according to method used to measure PA. Behavioral inhibition system
      seems to protect against inactivity among young women high in neuroticism.

PMID- 25386715
TI  - Associations of Sedentary Time with Fat Distribution in a High-Risk Population.
AB  - PURPOSE: The effect of sedentary behavior on regional fat deposition, independent
      of physical activity, remains equivocal. We examined the cross-sectional
      associations between objectively measured sedentary time and markers of regional
      fat distribution (heart, liver, visceral, subcutaneous, and total body fat) in a
      population at a high risk of type 2 diabetes mellitus (T2DM). METHODS:
      Participants were recruited from primary care to two diabetes prevention
      programs. Sedentary time (<25 counts per 15 s) was measured using ActiGraph GT3X
      accelerometers. Heart, liver, visceral, subcutaneous, and total body fat were
      quantified using magnetic resonance images. Fat volumes were calculated by
      multiplying the cross-sectional areas of the fat-containing pixels by the slice
      thickness. The liver fat percentage was measured using a representative region of
      interest created in the right lobe of the liver, avoiding the main portal veins.
      Linear regression models examined the association of sedentary time with markers
      of regional fat deposition. RESULTS: Sixty-six participants (age, 47.9 +/- 16.2
      yr; male, 50.0%) were included. After adjustment for several covariates,
      including glycemia, whole-body fat, and moderate-to-vigorous physical activity,
      each 30 min of sedentary time was associated with 15.7 cm higher heart fat (P =
      0.008), 1.2% higher liver fat (P = 0.026), and 183.7 cm higher visceral fat (P =
      0.039). CONCLUSIONS: This study provides new evidence suggesting that objectively
      measured sedentary behavior may have an independent association with heart,
      liver, and visceral fat in individuals at a high risk of T2DM.

PMID- 25386716
TI  - Automatic region-of-interest segmentation and registration of dynamic contrast
      enhanced images of colorectal tumors.
AB  - Dynamic contrast-enhanced (DCE) images can be acquired at multiple time points
      and multiple slice locations of a tumor. Image segmentation and registration are
      important preprocessing steps that can improve subsequent analysis of DCE images
      by kinetic modeling. An automatic system for region-of-interest segmentation and
      registration of DCE images is presented. Tissue segmentation is performed using a
      combination of thresholding and morphological operations, and further refined
      using shape information from consecutive images. The segmented regions are
      subsequently registered based on a mutual information method that accounts for
      possible tissue movement between slices. The proposed segmentation and
      registration methods are applied on actual DCE CT datasets to illustrate
      feasibility of practical implementation in the clinic. 

PMID- 25386718
TI  - Perturbative multireference configuration interaction (CI-MRPT2) calculations in
      a focused dynamical approach: a computational study of solvatochromism in
      pyrimidine.
AB  - We have investigated solvatochromic effects over a solvent series of increasing
      polarity on the prototype molecule pyrimidine as a solute species. The line shape
      profiles, obtained by a time-dependent approach based on quantum mechanical
      calculations performed over frames sampled from classical molecular dynamics
      trajectories, were directly compared to the available experimental bands. The
      multireference configuration interaction second-order perturbation (CI-MRPT2)
      calculations are in quantitative agreement with the experiment. The results also
      confirm how nonprotic solvents can be confidently modeled by continuous solvation
      models as the polarizable continuum model, whereas protic solvents, as water,
      require the inclusion of explicit solvent molecules to account for the effects of
      hydrogen bonds. 

PMID- 25386717
TI  - "Do not resuscitate" decisions in acute respiratory distress syndrome. A
      secondary analysis of clinical trial data.
AB  - RATIONALE: Factors and outcomes associated with end-of-life decision-making among
      patients during clinical trials in the intensive care unit are unclear.
      OBJECTIVES: We sought to determine patterns and outcomes of Do Not Resuscitate
      (DNR) decisions among critically ill patients with acute respiratory distress
      syndrome (ARDS) enrolled in a clinical trial. METHODS: We performed a secondary
      analysis of data from the ARDS Network Fluid and Catheter Treatment Trial
      (FACTT), collected between 2000 and 2005. We calculated mortality outcomes
      stratified by code status, and compared baseline characteristics of patients who
      became DNR during the trial with participants who remained full code.
      MEASUREMENTS AND MAIN RESULTS: Among 809 FACTT participants with a code status
      recorded, 232 (28.7%) elected DNR status. Specifically, 37 (15.9%) chose to
      withhold cardiopulmonary resuscitation alone, 44 (19.0%) elected to withhold some
      life support measures in addition to cardiopulmonary resuscitation, and 151
      (65.1%) had life support withdrawn. Admission severity of illness as measured by
      APACHE III score was strongly associated with election of DNR status (odds ratio,
      2.2; 95% confidence interval, 1.85-2.62; P < 0.0001). Almost all (97.0%; 225 of
      232) patients who selected DNR status died, and 79% (225 of 284) of patients who
      died during the trial were DNR. Among patients who chose DNR status but did not
      elect withdrawal of life support, 91% (74 of 81) died. CONCLUSIONS: The vast
      majority of deaths among clinical trial patients with ARDS were preceded by a DNR
      order. Unlike other studies of end-of-life decision-making in the intensive care
      unit, nearly all patients who became DNR died. The impact of variation of
      practice in end-of-life decision-making during clinical trials warrants further
      study.

PMID- 25386720
TI  - Inhibition of cPLA2 has neuroprotective effects on motoneuron and muscle atrophy
      following spinal cord injury.
AB  - Surviving motoneurons undergo dendritic atrophy after spinal cord injury (SCI),
      suggesting an important therapeutic target for neuroprotective strategies to
      improve recovery of function after SCI. Our previous studies showed that
      phospholipase A2 (PLA2) may play an important role in the pathogenesis of SCI. In
      the present study, we investigated whether blocking cPLA2 pharmacologically with
      arachidonyl trifluoromethyl ketone (ATK) or genetically using cPLA2 knockout (KO)
      mice attenuates motoneuron atrophy following SCI. C57BL/6 mice received either
      sham or contusive SCI at the T10 level. At 30 min after SCI, mice were treated
      with ATK or vehicle. Four weeks later, motoneurons innervating the vastus
      lateralis muscle of the quadriceps were labeled with cholera toxin-conjugated
      horseradish peroxidase, and dendritic arbors were reconstructed in three
      dimensions. Soma volume, motoneuron number, lesion volume, and tissue sparing
      were also assessed, as were muscle weight, fiber cross-sectional area, and motor
      endplate size and density. ATK administration reduced percent lesion volume and
      increased percent volume of spared white matter compared to the vehicle-treated
      control animals. SCI with or without ATK treatment had no effect on the number or
      soma volume of quadriceps motoneurons. However, SCI resulted in a decrease in
      dendritic length of quadriceps motoneurons in untreated animals, and this
      decrease was completely prevented by treatment with ATK. Similarly, the vastus
      lateralis muscle weights of untreated SCI animals were smaller than those of sham
      surgery controls, and these reductions were prevented by ATK treatment. No
      effects on fiber cross-sectional areas, motor endplate area or density were
      observed across treatment groups. Remarkably, genetically deleting cPLA2 in cPLA2
      KO mice attenuated dendritic atrophy after SCI. These findings suggest that after
      SCI, cord tissue damage and regressive changes in motoneuron and muscle
      morphology can be reduced by inhibition of cPLA2, further supporting a role for
      cPLA2 as a neurotherapeutic target for SCI treatment.

PMID- 25386719
TI  - eHealth literacy interventions for older adults: a systematic review of the
      literature.
AB  - BACKGROUND: eHealth resources offer new opportunities for older adults to access
      health information online, connect with others with shared health interests, and
      manage their health. However, older adults often lack sufficient eHealth literacy
      to maximize their benefit from these resources. OBJECTIVE: This review evaluates
      the research design, methods, and findings of eHealth literacy interventions for
      older adults. METHODS: A systematic review of peer-reviewed research articles
      from 28 databases in 9 fields was carried out in January 2013. Four rounds of
      screening of articles in these databases resulted in a final sample of 23
      articles. RESULTS: Findings indicated a significant gap in the literature for
      eHealth literacy interventions evaluating health outcomes as the outcome of
      interest, a lack of theory-based interventions, and few studies applied high
      quality research design. CONCLUSIONS: Our findings emphasize the need for
      researchers to develop and assess theory-based interventions applying high
      quality research design in eHealth literacy interventions targeting the older
      population.

PMID- 25386721
TI  - Effect of cooling condition on chemical vapor deposition synthesis of graphene on
      copper catalyst.
AB  - Here, we show that chemical vapor deposition growth of graphene on copper foil is
      strongly affected by the cooling conditions. Variation of cooling conditions such
      as cooling rate and hydrocarbon concentration in the cooling step has yielded
      graphene islands with different sizes, density of nuclei, and growth rates. The
      nucleation site density on Cu substrate is greatly reduced when the fast cooling
      condition was applied, while continuing methane flow during the cooling step also
      influences the nucleation and growth rate. Raman spectra indicate that the
      graphene synthesized under fast cooling condition and methane flow on cool-down
      exhibit superior quality of graphene. Further studies suggest that careful
      control of the cooling rate and CH4 gas flow on the cooling step yield a high
      quality of graphene. 

PMID- 25386722
TI  - Reduced production of OprM may promote oprD mutations and lead to imipenem
      resistance in Pseudomonas aeruginosa carrying an oprD-group 1A allele.
AB  - Resistance mechanisms in a group of carbapenemase-negative Pseudomonas aeruginosa
      that were susceptible to all antibiotics except carbapenems (carbapenem
      resistance-only P. aeruginosa [CROPA]) were studied. Ten genetically nonrelated
      CROPA isolates and their carbapenem-susceptible counterparts were further
      investigated. OprD production was demonstrated by protein electrophoresis in only
      1 of the 10 carbapenem-susceptible isolates, while the other 9 isolates showed
      hyperproduction of OprM. DNA sequencing of oprD revealed a shortened loop 7
      domain (group 1A allele) in eight carbapenem-susceptible isolates. Various oprD
      mutations, leading to early terminations, were found in 9 of the 10 CROPA
      isolates. RNA analysis demonstrated hyperexpression of oprM with normal
      expression of mexA in eight of the carbapenem-susceptible isolates, while in
      seven of their CROPA counterparts, the oprM expression was significantly reduced.
      Deletion of oprM was performed in two pairs of representative isolates. Selection
      of imipenem resistant variants by a disc assay indicated that the lost-of
      function mutations in oprD occurred relatively faster in the DeltaoprM mutants
      compared with their corresponding parent strains. Under selection pressure,
      reduced production of OprM may promote the selection of spontaneous changes in
      oprD, resulting in the carbapenem resistance in a group of pan-susceptible P.
      aeruginosa isolates characterized by harboring an oprD-group 1A allele. 

PMID- 25386723
TI  - Sirex woodwasp: a model for evolving management paradigms of invasive forest
      pests.
AB  - The Sirex woodwasp, Sirex noctilio, and its fungal mutualist, Amylostereum
      areolatum, together constitute one of the most damaging invasive pests of pine.
      Despite a century of research and well-established management programs, control
      remains unpredictable and spread continues to new areas. Variable success in
      managing this pest has been influenced by complex invasion patterns, the
      multilayered nature of biological interactions, the varying local ecologies, and
      microevolutionary population processes in both the biocontrol organisms and in
      the wasps. Recent research findings are challenging the historical perspectives
      on methods to manage the Sirex woodwasp, calling for management programs to
      incorporate the variable local dynamics affecting this pest complex. In this
      regard, the Sirex woodwasp provides a superb model to illustrate the need for a
      different approach to develop efficient and sustainable management tools to deal
      with the growing and global nature of pest invasions in forests and plantations. 

PMID- 25386724
TI  - Trail pheromones: an integrative view of their role in social insect colony
      organization.
AB  - Trail pheromones do more than simply guide social insect workers from point A to
      point B. Recent research has revealed additional ways in which they help to
      regulate colony foraging, often via positive and negative feedback processes that
      influence the exploitation of the different resources that a colony has knowledge
      of. Trail pheromones are often complementary or synergistic with other
      information sources, such as individual memory. Pheromone trails can be composed
      of two or more pheromones with different functions, and information may be
      embedded in the trail network geometry. These findings indicate remarkable
      sophistication in how trail pheromones are used to regulate colony-level
      behavior, and how trail pheromones are used and deployed at the individual level.

PMID- 25386725
TI  - Bionomics of temperate and tropical Culicoides midges: knowledge gaps and
      consequences for transmission of Culicoides-borne viruses.
AB  - Culicoides midges are abundant hematophagous flies that vector arboviruses of
      veterinary and medical importance. Dramatic changes in the epidemiology of
      Culicoides-borne arboviruses have occurred since 1998, including the emergence of
      exotic viruses in northern temperate regions, increases in global disease
      incidence, and enhanced virus diversity in tropical zones. Drivers may include
      changes in climate, land use, trade, and animal husbandry. New Culicoides species
      and new wild reservoir hosts have been implicated in transmission, highlighting
      the dynamic nature of pathogen-vector-host interactions. Focusing on potential
      vector species worldwide and key elements of vectorial capacity, we review the
      sensitivity of Culicoides life cycles to abiotic and biotic factors. We consider
      implications for designing control measures and understanding impacts of
      environmental change in different ecological contexts. Critical geographical,
      biological, and taxonomic knowledge gaps are prioritized. Recent developments in
      genomics and mathematical modeling may enhance ecological understanding of these
      complex arbovirus systems. 

PMID- 25386726
TI  - Benefits of a ball and chain: simple environmental enrichments improve welfare
      and reproductive success in farmed American mink (Neovison vison).
AB  - Can simple enrichments enhance caged mink welfare? Pilot data from 756 sub-adults
      spanning three colour-types (strains) identified potentially practical
      enrichments, and suggested beneficial effects on temperament and fur-chewing. Our
      main experiment started with 2032 Black mink on three farms: from each of 508
      families, one juvenile male-female pair was enriched (E) with two balls and a
      hanging plastic chain or length of hose, while a second pair was left as a non
      enriched (NE) control. At 8 months, more than half the subjects were killed for
      pelts, and 302 new females were recruited (half enriched: 'late E'). Several
      signs of improved welfare or productivity emerged. Access to enrichment increased
      play in juveniles. E mink were calmer (less aggressive in temperament tests;
      quieter when handled; less fearful, if male), and less likely to fur-chew,
      although other stereotypic behaviours were not reduced. On one farm, E females
      had lower cortisol (inferred from faecal metabolites). E males tended to copulate
      for longer. E females also weaned more offspring: about 10% more juveniles per E
      female, primarily caused by reduced rates of barrenness ('late E' females also
      giving birth to bigger litters on one farm), effects that our data cautiously
      suggest were partly mediated by reduced inactivity and changes in temperament.
      Pelt quality seemed unaffected, but E animals had cleaner cages. In a subsidiary
      side-study using 368 mink of a second colour-type ('Demis'), similar temperament
      effects emerged, and while E did not reduce fur-chewing or improve reproductive
      success in this colour-type, E animals were judged to have better pelts. Overall,
      simple enrichments were thus beneficial. These findings should encourage welfare
      improvements on fur farms (which house 60-70 million mink p.a.) and in breeding
      centres where endangered mustelids (e.g. black-footed ferrets) often reproduce
      poorly. They should also stimulate future research into more effective practical
      enrichments. 

PMID- 25386728
TI  - Drug delivery and nanodetection in lung cancer.
AB  - Lung carcinoma is the most widespread type of cancer worldwide, and is
      responsible for more deaths than other types of cancer. Lung cancer remains the
      chief cause of cancer-related deaths in both men and women worldwide, and is
      increasingly common in women. Each year, the number of deaths from lung cancer is
      greater than the number due to breast and colorectal cancer combined. Lung cancer
      accounted for 13% (1.6 million) of the total cases and 18% (1.4 million) of the
      deaths in 2008. In Iran, lung cancer is one of the five leading tumors. Among
      females, it was the fourth most commonly diagnosed cancer, and the second leading
      cause of cancer death. Nanotechnology can be defined as the science and
      engineering involved in the design, characterization, and application of
      materials and devices whose smallest functional organization in at least one
      dimension is on the nanometer scale, i.e. one billionth of a meter. It is an
      exciting multidisciplinary field that involves the design and engineering of nano
      objects or nanotools with diameters less than 500 nanometers (nm), and it is one
      of the most interesting fields of the 21st century. Nanotechnology also offers
      the ability to detect diseases, such as tumors, much earlier than ever
      imaginable. This article presents nano devices for lung cancer detection and drug
      delivery systems. 

PMID- 25386727
TI  - Mind-controlled transgene expression by a wireless-powered optogenetic designer
      cell implant.
AB  - Synthetic devices for traceless remote control of gene expression may provide new
      treatment opportunities in future gene- and cell-based therapies. Here we report
      the design of a synthetic mind-controlled gene switch that enables human brain
      activities and mental states to wirelessly programme the transgene expression in
      human cells. An electroencephalography (EEG)-based brain-computer interface (BCI)
      processing mental state-specific brain waves programs an inductively linked
      wireless-powered optogenetic implant containing designer cells engineered for
      near-infrared (NIR) light-adjustable expression of the human glycoprotein SEAP
      (secreted alkaline phosphatase). The synthetic optogenetic signalling pathway
      interfacing the BCI with target gene expression consists of an engineered NIR
      light-activated bacterial diguanylate cyclase (DGCL) producing the orthogonal
      second messenger cyclic diguanosine monophosphate (c-di-GMP), which triggers the
      stimulator of interferon genes (STING)-dependent induction of synthetic
      interferon-beta promoters. Humans generating different mental states (biofeedback
      control, concentration, meditation) can differentially control SEAP production of
      the designer cells in culture and of subcutaneous wireless-powered optogenetic
      implants in mice. 

PMID- 25386729
TI  - A new PANI biosensor based on catalase for cyanide determination.
AB  - Cyanide is one of the most widespread of compounds measured in environmental
      analysis due to their toxic effects on environment and health. We report a highly
      sensitive, reliable, selective amperometric sensor for determination of cyanide,
      using a polyaniline conductive polymer. The enzyme catalase was immobilized by
      electropolymerization. The steps during the immobilization were controlled by
      electrochemical impedance spectroscopy. Optimum pH, temperature, aniline
      concentration, enzyme concentration, and the number of scans obtained during
      electropolymerization, were investigated. In addition, the cyanide present in
      artificial waste water samples was determined. In the characterization studies of
      the biosensor, some parameters such as reproducibility and storage stability,
      were analyzed. 

PMID- 25386730
TI  - Effects of titanium dioxide nanoparticles on alpha-synuclein aggregation and the
      ubiquitin-proteasome system in dopaminergic neurons.
AB  - Dopaminergic neurons (PC12 cells) were treated with different doses of titanium
      dioxide nanoparticles (TiO2-NPs), to investigate their effects on alpha-Synuclein
      (alpha-Syn) aggregation and their mechanism of action. Western blotting and
      immunofluorescent staining were performed. Exposure to TiO2-NPs increased alpha
      Syn expression (p < 0.05) and induced dose-dependent alpha-Syn aggregation.
      Pretreatment with N-acetylcysteine partially inhibited alpha-Syn expression
      induced by a 200 MUg/ml dose of TiO2-NPs. TiO2-NPs reduced the expressions of
      parkin and ubiquitin C-terminal hydrolase protein, and were associated with
      oxidative stress in PC12 cells. Dysfunction of the ubiquitin-proteasome system
      also contributed to alpha-Syn aggregation. The potentially neurotoxic TiO2-NPs
      may cause Parkinson's disease. 

PMID- 25386731
TI  - Dietary Intake, Anthropometric Characteristics, and Iron and Vitamin D Status of
      Female Adolescent Ballet Dancers Living in New Zealand.
AB  - Ballet dancing is a multifaceted activity requiring muscular power, strength,
      endurance, flexibility, and agility; necessitating demanding training schedules.
      Furthermore dancers may be under aesthetic pressure to maintain a lean physique,
      and adolescent dancers require extra nutrients for growth and development. This
      cross-sectional study investigated the nutritional status of 47 female adolescent
      ballet dancers (13-18 years) living in Auckland, New Zealand. Participants who
      danced at least 1 hr per day 5 days per week completed a 4-day estimated food
      record, anthropometric measurements (Dual-energy X-ray Absorptiometry) and
      hematological analysis (iron and vitamin D). Mean BMI was 19.7 +/- 2.4 kg/m2 and
      percentage body fat, 23.5 +/- 4.1%. The majority (89.4%) of dancers had a healthy
      weight (5th-85th percentile) using BMI-for-age growth charts. Food records showed
      a mean energy intake of 8097.3 +/- 2155.6 kJ/day (48.9% carbohydrate, 16.9%
      protein, 33.8% fat, 14.0% saturated fat). Mean carbohydrate and protein intakes
      were 4.8 +/- 1.4 and 1.6 +/- 0.5 g/kg/day respectively. Over half (54.8%) of
      dancers consumed less than 5 g carbohydrate/kg/day, and 10 (23.8%) less than 1.2
      g protein/kg/day. Over 60% consumed less than the estimated average requirement
      for calcium, folate, magnesium and selenium. Thirteen (28.3%) dancers had
      suboptimal iron status (serum ferritin (SF) < 20 MUg/L). Of these, four had iron
      deficiency (SF < 12 MUg/L, hemoglobin (Hb) >= 120 g/L) and one iron deficiency
      anemia (SF < 12 MUg/L, Hb < 120 g/L). Mean serum 25-hydroxy vitamin D was 75.1 +/
      18.6 nmol/L, 41 (91.1%) had concentrations above 50 nmol/L. Female adolescent
      ballet dancers are at risk for iron deficiency, and possibly inadequate nutrient
      intakes.

PMID- 25386732
TI  - Quantitative serine protease assays based on formation of copper(II)-oligopeptide
      complexes.
AB  - A quantitative protease assay based on the formation of a copper-oligopeptide
      complex is developed. In this assay, when a tripeptide GGH fragment is cleaved
      from an oligopeptide chain by serine proteases, the tripeptide quickly forms a
      pink GGH/Cu(2+) complex whose concentration can be determined quantitatively by
      using UV-Vis spectroscopy. Therefore, activities of serine proteases can be
      determined from the formation rate of the GGH/Cu(2+) complex. This principle can
      be used to detect the presence of serine protease in a real-time manner, or
      measure proteolytic activities of serine protease cleaving different oligopeptide
      substrates. For example, by using this assay, we demonstrate that trypsin, a
      model serine protease, is able to cleave two oligopeptides GGGGKGGH () and
      GGGGRGGH (). However, the specificity constant (kcat/Km) for is higher than that
      of (6.4 * 10(3) mM(-1) min(-1)vs. 1.3 * 10(3) mM(-1) min(-1)). This result shows
      that trypsin is more specific toward arginine (R) than lysine (K) in the
      oligopeptide sequence. 

PMID- 25386733
TI  - Using nonlinear tools to evaluate movement of fragile objects.
AB  - We investigated the movement strategies of young, healthy participants (7 men/7
      women) during the movement of a fragile object using nonlinear analysis. The
      kinematic variables of position, velocity, and acceleration were quantified using
      largest Lyapunov exponent (LyE) and approximate entropy (ApEn) analysis to
      identify the structure of their movement variability and movement predictability,
      respectively. Subjects performed a total of 15 discrete trials of an upper
      extremity movement task without crushing the object at each fragility condition,
      using each hand (left/right). We tested four fragility conditions hypothesizing
      that an increase in fragility would result in higher movement predictability and
      decreased temporal variability. Comparisons between the structure of movement
      variability and movement predictability were based on fragility condition,
      handedness, and kinematic measures. In this specific population, object fragility
      and participant handedness did not significantly impact the structure of movement
      variability (LyE) in the primary direction of movement (Z direction), although
      some effects were observed in the anterior/posterior directions. ApEn values were
      minimized across conditions, showing increased movement predictability, and is
      suggested for the analysis of discrete kinematic movements. In healthy
      populations, the results of this study suggest minimal effects on task
      performance and movement predictability as a result of object fragility. 

PMID- 25386734
TI  - Associations Between Home Environment and After-School Physical Activity and
      Sedentary Time Among 6th Grade Children.
AB  - This study examined associations of various elements of the home environment with
      after-school physical activity and sedentary time in 671 6th-grade children (Mage
      = 11.49 +/- 0.5 years). Children's after-school total physical activity, moderate
      to-vigorous physical activity, and sedentary time were measured by accelerometry.
      Parents completed surveys assessing elements of the home social and physical
      environment. Mixed-model regression analyses were used to examine the
      associations between each element of the home environment and children's after
      school physical activity and sedentary time. Availability of home physical
      activity resources was associated positively with after-school total physical
      activity and negatively with after-school sedentary time in boys. Parental
      support was associated positively with after-school total physical activity and
      MVPA and negatively with after-school sedentary time in girls. The home physical
      environment was associated with boys' after-school physical activity and
      sedentary time, whereas the home social environment was associated with girls'
      after-school physical activity and sedentary time. 

PMID- 25386735
TI  - First TILLING platform in Cucurbita pepo: a new mutant resource for gene function
      and crop improvement.
AB  - Although the availability of genetic and genomic resources for Cucurbita pepo has
      increased significantly, functional genomic resources are still limited for this
      crop. In this direction, we have developed a high throughput reverse genetic
      tool: the first TILLING (Targeting Induced Local Lesions IN Genomes) resource for
      this species. Additionally, we have used this resource to demonstrate that the
      previous EMS mutant population we developed has the highest mutation density
      compared with other cucurbits mutant populations. The overall mutation density in
      this first C. pepo TILLING platform was estimated to be 1/133 Kb by screening
      five additional genes. In total, 58 mutations confirmed by sequencing were
      identified in the five targeted genes, thirteen of which were predicted to have
      an impact on the function of the protein. The genotype/phenotype correlation was
      studied in a peroxidase gene, revealing that the phenotype of seedling homozygous
      for one of the isolated mutant alleles was albino. These results indicate that
      the TILLING approach in this species was successful at providing new mutations
      and can address the major challenge of linking sequence information to biological
      function and also the identification of novel variation for crop breeding. 

PMID- 25386736
TI  - Short communication: Apoptosis pathways in HIV-1-infected patients before and
      after highly active antiretroviral therapy: relevance to immune recovery.
AB  - Investigations into apoptotic pathways, intrinsic and extrinsic, and the effects
      of highly active antiretroviral therapy (HAART) on T cell death via those
      pathways may provide insight into the mechanisms of and barriers to immune
      recovery. HIV-1-infected patients were enrolled into a randomized, controlled
      study of the immune effects of a lopinavir/ritonavir (LPV/r)-based versus an
      efavirenz (EFV)-based HAART regimen in antiretroviral-naive subjects with CD4(+)
      counts <350 cells/mm(3). Patients were randomized to receive TDF/FTC/EFZ or
      TDF/FTC plus LPV/r. Fourteen patients were enrolled and 10 patients completed 6
      months of therapy as per the protocol. CD4(+) counts were measured before and
      during HAART therapy. We isolated T cell subsets to measure ex vivo apoptosis by
      propidium iodide staining. We also assessed caspase activation for the intrinsic
      and extrinsic pathways of apoptosis, as well as effector caspase activation. We
      also measured mitochondrial membrane potential. Cells were analyzed by flow
      cytometry. All patients had increased activation of caspase 8 (extrinsic
      pathway), caspase 9 (intrinsic pathway), effector caspases 3/7, and low
      mitochondrial membrane potential at baseline compared to controls. By 4 weeks,
      there was a decrease in activation of all caspases, but little further decrease
      by week 24. T cell mitochondrial membrane potential did not increase until week
      12, but continued to increase until week 24. The only predictor of CD4(+) count
      increase was the increase in mitochondrial membrane potential of naive cells at 6
      months (r=0.66, p=0.038). This suggests that positive selection of naive CD4(+) T
      cells in the thymus is the major determinant of CD4(+) recovery.

PMID- 25386737
TI  - Improved survival for anatomic total shoulder prostheses.
AB  - BACKGROUND AND PURPOSE: Previously, implant survival of total shoulder prostheses
      was reported to be inferior to that of hemiprostheses. However, the use of total
      prostheses has increased in Norway due to reported good functional results. On
      this background, we wanted to study implant survival of 4 major shoulder
      prosthesis types in Norway between 1994 and 2012. PATIENTS AND METHODS: The study
      population comprised 4,173 patients with shoulder replacements reported to the
      Norwegian Arthroplasty Register, including 2,447 hemiprostheses (HPs), 444
      anatomic total prostheses (ATPs), 454 resurfacing prostheses (RPs), and 828
      reversed total prostheses (RTPs). Three time periods were compared: 1994-1999,
      2000-2005, and 2006-2012. Kaplan-Meier failure curves were used to compare
      implant failure rates for subgroups of patients, and adjusted risks of revision
      were calculated using Cox regression analysis. RESULTS: For prostheses inserted
      from 2006 through 2012, the 5-year survival rates were 95% for HPs (as opposed to
      94% in 1994-1999), 95% for ATPs (75% in 1994-1999), 87% for RPs (96% in 1994
      1999), and 93% for RTPs (91% in 1994-1999). During the study period, the implant
      survival improved significantly for ATPs (p < 0.001). A tendency of better
      results with acute fracture and worse results in sequelae after previous
      fractures was seen in all time periods. INTERPRETATION: The 5-year implant
      survival rates were good with all prosthesis types, and markedly improved for
      anatomic total prostheses in the last 2 study periods. The better functional
      results with total shoulder prostheses than with hemiprostheses support the trend
      towards increased use of total shoulder prostheses.

PMID- 25386738
TI  - Comparison of planned and achieved implant position in total knee arthroplasty
      with patient-specific positioning guides.
AB  - BACKGROUND AND PURPOSE: Intraoperatively, patient-specific positioning guides
      (PSPGs) represent the preoperatively planned alignment. We investigated the
      degree of correlation between preoperative planning and the alignment achieved
      postoperatively with the PSPG technique. PATIENTS AND METHODS: TKAs performed
      with the PSPG technique between 2009 and 2011 were included. 39 patients (42
      TKAs) volunteered for a postoperative CT scan. 2 independent observers performed
      the postoperative CT measurements. Preoperative component angles (target angles)
      in the coronal and axial planes were defined as 0 degrees, and in the sagittal
      plane on average 2.8 degrees for the femoral component and 3 degrees for the
      tibial component. A postoperative full-length standing anteroposterior radiograph
      was carried out in 41 TKAs. RESULTS: The femoral component was on average 1.2 (SD
      1.5) degrees in varus, 4.4 (SD 4.0) degrees in flexion, and 0.5 (SD 1.4) degrees
      in external rotation. The tibial component was on average 0.4 (SD 2.5) degrees in
      varus and 3.7 (SD 2.3) degrees in flexion. A statistically significant difference
      between the target (preoperative software plan) and postoperative CT measurement
      was found for the femoral component angle in the frontal plane (p < 0.001; CI:
      0.8-1.7), the sagittal plane (p = 0.01; CI -5.6 to -3.1), and the axial plane (p
      = 0.03; CI: 0.04-0.88). HKA angles were greater than 3 degrees from the neutral
      axis in 10 of the 41 cases. INTERPRETATION: We found our postoperative component
      alignment angles to be close to the software plan, especially for the tibial
      component. However, we found outliers in all planes and we cannot therefore
      conclude that the PSPG technique is a method that reproduces preoperatively
      planned alignment in a consistent manner.

PMID- 25386739
TI  - The effect of ion-pair formation combined with penetration enhancers on the skin
      permeation of loxoprofen.
AB  - CONTEXT: Loxoprofen (LOXO) is a non-steroidal anti-inflammatory drug. Repeated
      oral administrations induce gastrointestinal side effects. Patches are a
      promising alternative. OBJECTIVE: The aim of this study was to investigate the
      effects of organic amines on the skin permeation of LOXO and finally design a
      patch with a comparable permeation profile and pharmacodynamic effects to the
      commercial LOXONA(r) plaster. MATERIALS AND METHODS: The effects of organic
      amines were assessed by flux values of LOXO from isopropyl myristate (IPM), using
      horizontal diffusion cell and rabbit skin. FTIR spectroscopy was used to confirm
      ion-pair formation. Anti-inflammatory and analgesic activity assessments were
      performed in the adjuvant arthritis rat model and acetic acid-induced writhing
      syndrome in mouse, separately. RESULTS AND DISCUSSION: Results showed that
      triethylamine (TEA) was the most potential candidate in IPM, with the highest
      flux of 499.75 +/- 32.40 ug/cm(2)/h. In patch, the highest flux of 369.37 +/-
      34.32 ug/cm(2)/h was still obtained by LOXO-TEA. Combined with penetration
      enhancers, the cumulative amounts were further increased in presence of 5% IPM,
      which exhibited a flux of 840.04 +/- 66.38 ug/cm(2)/h as two times of the
      commercial one. Ultimately, anti-inflammatory and analgesic activity assessment
      presented that a comparable pharmacodynamic activity with the commercial one
      could be obtained by the patch we designed. Additionally, we also found that LOXO
      patch applied topically exerted a systemic effect, and the effect was dose
      dependent. CONCLUSION: It was feasible for LOXO patch design by combination of
      ion-pair technology and chemical enhancers.

PMID- 25386740
TI  - Assessment of simvastatin niosomes for pediatric transdermal drug delivery.
AB  - The prevalence of childhood dyslipidemia increases and is considered as an
      important risk factor for the incidence of cardiovascular disease in the
      adulthood. To improve dosing accuracy and facilitate the determination of dosing
      regimens in function of the body weight, the proposed study aims at preparing
      transdermal niosomal gels of simvastatin as possible transdermal drug delivery
      system for pediatric applications. Twelve formulations were prepared to screen
      the influence of formulation and processing variables on critical niosomal
      characteristics. Nano-sized niosomes with 0.31 MUm number-weighted size displayed
      highest simvastatin release rate with 8.5% entrapment capacity. The niosomal
      surface coverage by negative charges was calculated according to Langmuir
      isotherm with n = 0.42 to suggest that the surface association was site
      independent, probably producing surface rearrangements. Hypolipidemic activities
      after transdermal administration of niosomal gels to rats showed significant
      reduction in cholesterol and triglyceride levels while increasing plasma high
      density lipoproteins concentration. Bioavailability estimation in rats revealed
      an augmentation in simvastatin bioavailability by 3.35 and 2.9 folds from
      formulation F3 and F10, respectively, compared with oral drug suspension. Hence,
      this transdermal simvastatin niosomes not only exhibited remarkable potential to
      enhance its bioavailability and hypolipidemic activity but also considered a
      promising pediatric antihyperlipidemic formulation. 

PMID- 25386741
TI  - Cross-Shift Changes in Lung Function Among Palestinian Farmers During High- and
      Low-Exposure Periods to Pesticides: A Longitudinal Study.
AB  - The purpose of this study was to study cross-shift changes of lung function in
      relation to pesticide use. One hundred and ninety-five male farmers, from a total
      of 250 farmers, performed lung function tests both pre- and post-shift during
      high- and low-pesticide-exposure periods. There were no associations between lung
      function differences across shifts and estimated quantity of pesticides used.
      However, the cross-shift reduction in forced expiratory volume in 1 second (FEV1;
      DeltaFEV1) was more pronounced during the period when pesticides were used on a
      larger scale, September 2006, compared with the exposure period with a lower
      level of pesticide use, April 2007, +50 mL (95% confidence interval [CI]: +24,
      +76) and +17 mL (95% CI: -13, +48), respectively. This contrast was statistically
      significant only among the subset of never-smoking participants below 50 years of
      age. This finding suggests a possible obstructive effect of pesticide exposure on
      lung function among this rural male population in Palestine. A follow-up of
      farmers' lung function in this part of the world along with high-quality
      measurements of exposure is needed.

PMID- 25386742
TI  - A pilot study of stimulant medication for adults with attention
      deficit/hyperactivity disorder (ADHD) who are parents of adolescents with ADHD:
      the acute effects of stimulant medication on observed parent-adolescent
      interactions.
AB  - OBJECTIVE: This study explores the use of stimulant medication for parents with
      attention-deficit/hyperactivity disorder (ADHD) who also have adolescents with
      ADHD. METHODS: Five parents, diagnosed with ADHD, had their dose of
      lisdexamfetamine (LDX) titrated to optimal effect. Next, parents and their
      adolescents completed two interactions, once when parents were on placebo and
      once when parents were on optimal dose of LDX, to assess acute effects of
      parental medication on parenting during a neutral discussion (NeuDiss), a problem
      discussion (ProbDiss), and a homework task (HW). RESULTS: Parents demonstrated a
      significant decrease in the ratio of commands to total verbalizations during the
      NeuDiss on LDX compared with placebo. Although no other statistically significant
      effects emerged at the p<0.05 level, moderate to large effects of medication on
      some aspects of parenting related to the amount and timing of speech (i.e., total
      verbalizations, total commands, ratio of commands to total verbalizations, and
      responsiveness) emerged and varied by task. Parental stimulant medication did not
      appear to impact the content of parents' speech (i.e., use of negative talk or
      praise). CONCLUSIONS: These results add to a growing literature suggesting that
      treatment for parental ADHD may impact parenting performance, and suggest that
      attention to parental ADHD in treatment for adolescents with ADHD may possibly
      enhance family functioning.

PMID- 25386743
TI  - Diagnostic accuracy of siemens ADVIA 2120i's five hematological parameters in the
      identification of pediatric acute lymphoblastic leukemia.

PMID- 25386744
TI  - Cytochrome P450 expression in mouse brain: specific isoenzymes involved in Phase
      I metabolizing system of porphyrinogenic agents in both microsomes and
      mitochondria.
AB  - Brain cytochrome P450 (CYP) metabolizes a variety of drugs to produce their
      pharmacological effects within the brain. We have previously observed that
      porphyrinogenic agents altered CYP levels in brain. The aim of this work was to
      further study the involvement of mice brain mitochondrial and microsomal Phase I
      drug metabolizing system when porphyrinogenic agents, such as Enflurane,
      Isoflurane, allylisopropylacetamide, veronal, ethanol, and Griseofulvin were
      administered. To this end, CYP2E1, CYP2B1, and CYP3A4 expression were measured.
      NADPH cytochrome P450 reductase (CPR) expression was also determined. Western
      Blots were performed in microsomes and mitochondria of whole brain. Some of the
      drugs studied altered expression mainly in microsomes. Chronic Isoflurane
      augmented mitochondrial isoform, although this anaesthetic diminished microsomal
      expression. Ethanol and topical Griseofulvin affected expression in microsomes
      but not in mitochondria. CYP2E1 mitochondrial activity was induced by acute
      Enflurane; while the activity of the microsomal protein was enhanced in
      alcoholised animals. Ethanol also induced CYP2E1 expression in microsomes,
      although Isoflurane provoked opposite effects in mitochondria and microsomes.
      Expression of CPR was also induced. Several reports support an emergent role of
      CYP enzymes in the pathogenesis of neurological disorders, so CYP response in
      brain could be one of the multiples factors influencing porphyria acute attacks. 

PMID- 25386745
TI  - An artemisinin derivative of praziquantel as an orally active antischistosomal
      agent.
AB  - BACKGROUND: Schistosomiasis is a major health problem in tropical and sub
      tropical areas caused by species of trematode belonging to the genus Schistosoma.
      The treatment and control of this disease has been relying on the use of a single
      drug praziquantel. However, the drug resistance concern urged the development of
      new drugs against schistosoma. Here, we report our systematic biological
      evaluation of DW-3-15, a new lead compound developed based on our conjugation
      design rationale as an effective anti-schistosomal agent. METHODOLOGY/PRINCIPAL
      FINDINGS: The antischistosomal activity of DW-3-15 was systematically evaluated
      in S. japonicum infected mouse model for its stage-sensitivity and dose response.
      The results revealed that DW-3-15 exhibited 60-85% worm reduction rate against
      different development stage of worm. Scanning electron microscopy (SEM)
      observation indicated that DW-3-15 may damage to the tegument of male
      schistosomes. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that DW-3-15
      showed potent anti-schistosomal activities in vivo. The results strongly support
      our conjugation design strategy of artemisinin analogs and further development of
      DW-3-15 as a new lead compound as anti-schistosomal agent.

PMID- 25386747
TI  - A risk score for predicting pulmonary hypertension in patients with non
      transfusion-dependent thalassemia in northeastern Thailand: The E-SAAN score.
AB  - INTRODUCTION: Pulmonary hypertension (PH) is a major complication in patients
      with non-transfusion-dependent thalassemia (NTDT). The risk score was developed
      to be a screening test for PH risk in these patients. METHODS: A multi-center
      study was conducted in patients with NTDT aged >=10 years old. PH risk was
      defined as tricuspid regurgitation velocity >2.9 m/s by echocardiography. The
      clinical parameters significantly associated with PH were entered into the
      logistic regression model. RESULTS: The E-SAAN score included (1) age >35 years
      (2.5 points), (2) time after splenectomy >5 years (2.5 points), and (3) beta
      thalassemia/hemoglobin E (2 points). Using the cut-off point of 4.5 points, the
      score showed a good discrimination in the validating group with an area under
      receiver-operating characteristics curve of 0.88 (95% CI 0.8-0.95). CONCLUSION:
      The E-SAAN score is a simple and practical score which can be used as a screening
      test for PH risk in patients with NTDT.

PMID- 25386746
TI  - Access to healthcare, HIV/STI testing, and preferred pre-exposure prophylaxis
      providers among men who have sex with men and men who engage in street-based sex
      work in the US.
AB  - BACKGROUND: Pre-exposure prophylaxis (PrEP) is a promising strategy for HIV
      prevention among men who have sex with men (MSM) and men who engage in sex work.
      But access will require routine HIV testing and contacts with healthcare
      providers. This study investigated men's healthcare and HIV testing experiences
      to inform PrEP implementation. METHODS: We conducted 8 focus groups (n = 38) in
      2012 and 56 in-depth qualitative interviews in 2013-14 with male sex workers
      (MSWs) (n = 31) and other MSM (n = 25) in Providence, RI. MSWs primarily met
      clients in street-based sex work venues. Facilitators asked participants about
      access to healthcare and HIV/STI testing, healthcare needs, and preferred PrEP
      providers. RESULTS: MSWs primarily accessed care in emergency rooms (ERs),
      substance use clinics, correctional institutions, and walk-in clinics. Rates of
      HIV testing were high, but MSWs reported low access to other STI testing, low
      insurance coverage, and unmet healthcare needs including primary care, substance
      use treatment, and mental health services. MSM not engaging in sex work were more
      likely to report access to primary and specialist care. Rates of HIV testing
      among these MSM were slightly lower, but they reported more STI testing, more
      insurance coverage, and fewer unmet needs. Preferred PrEP providers for both
      groups included primary care physicians, infectious disease specialists, and
      psychiatrists. MSWs were also willing to access PrEP in substance use treatment
      and ER settings. CONCLUSIONS: PrEP outreach efforts for MSWs and other MSM should
      engage diverse providers in many settings, including mental health and substance
      use treatment, ERs, needle exchanges, correctional institutions, and HIV testing
      centers. Access to PrEP will require financial assistance, but can build on
      existing healthcare contacts for both populations.

PMID- 25386748
TI  - Design and validation of DNA libraries for multiplexing proximity ligation
      assays.
AB  - Here, we present an in silico, analytical procedure for designing and testing
      orthogonal DNA templates for multiplexing of the proximity ligation assay (PLA).
      PLA is a technology for the detection of protein interactions, post-translational
      modifications, and protein concentrations. To enable multiplexing of the PLA, the
      target information of antibodies was encoded within the DNA template of a PLA,
      where each template comprised four single-stranded DNA molecules. Our DNA design
      procedure followed the principles of minimizing the free energy of DNA cross
      hybridization. To validate the functionality, orthogonality, and efficiency of
      the constructed template libraries, we developed a high-throughput solid-phase
      rolling-circle amplification assay and solid-phase PLA on a microfluidic
      platform. Upon integration on a microfluidic chip, 640 miniaturized pull-down
      assays for oligonucleotides or antibodies could be performed in parallel together
      with steps of DNA ligation, isothermal amplification, and detection under
      controlled microenvironments. From a large computed PLA template library, we
      randomly selected 10 template sets and tested all DNA combinations for cross
      reactivity in the presence and absence of antibodies. By using the microfluidic
      chip application, we determined rapidly the false-positive rate of the design
      procedure, which was less than 1%. The combined theoretical and experimental
      procedure is applicable for high-throughput PLA studies on a microfluidic chip. 

PMID- 25386749
TI  - Intravenous remifentanil versus epidural ropivacaine with sufentanil for labour
      analgesia: a retrospective study.
AB  - Remifentanil with appropriate pharmacological properties seems to be an ideal
      alternative to epidural analgesia during labour. A retrospective cohort study was
      undertaken to assess the efficacy and safety of remifentanil intravenous patient
      controlled analgesia (IVPCA) compared with epidural analgesia. Medical records of
      370 primiparas who received remifentanil IVPCA or epidural analgesia were
      reviewed. Pain and sedation scores, overall satisfaction, the extent of pain
      control, maternal side effects and neonatal outcome as primary observational
      indicators were collected. There was a significant decline of pain scores in both
      groups. Pain reduction was greater in the epidural group throughout the whole
      study period (0 ~ 180 min) (P < 0.0001), and pain scores in the remifentanil
      group showed an increasing trend one hour later. The remifentanil group had a
      lower SpO2 (P < 0.0001) and a higher sedation score (P < 0.0001) within 30 min
      after treatment. The epidural group had a higher overall satisfaction score (3.8
      +/- 0.4 vs. 3.7 +/- 0.6, P = 0.007) and pain relief score (2.9 +/- 0.3 vs. 2.8 +/
      0.4, P < 0.0001) compared with the remifentanil group. There was no significant
      difference on side effects between the two groups, except that a higher rate of
      dizziness (1% vs. 21.8%, P < 0.0001) was observed during remifentanil analgesia.
      And logistic regression analysis demonstrated that nausea, vomiting were
      associated with oxytocin usage and instrumental delivery, and dizziness was
      associated to the type and duration of analgesia. Neonatal outcomes such as Apgar
      scores and umbilical-cord blood gas analysis were within the normal range, but
      umbilical pH and base excess of neonatus in the remifentanil group were
      significantly lower. Remifentanil IVPCA provides poorer efficacy on labor
      analgesia than epidural analgesia, with more sedation on parturients and a trend
      of newborn acidosis. Despite these adverse effects, remifentanil IVPCA can still
      be an alternative option for labor analgesia under the condition of one-to-one
      bedside care, continuous monitoring, oxygen supply and preparation for neonatal
      resuscitation.

PMID- 25386750
TI  - Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of
      the mouse nicotinic acetylcholine receptor.
AB  - High-affinity blockers for an ion channel often have complex molecular structures
      that are synthetically challenging and/or laborious. Here we show that high
      affinity blockers for the mouse nicotinic acetylcholine receptor (AChR) can be
      prepared from a structurally simple material, poly(ethylene glycol) (PEG). The
      PEG-based blockers (PQ1-5), comprised of a flexible octa(ethylene glycol)
      scaffold and two terminal quaternary ammonium groups, exert low- to sub
      micromolar affinities for the open AChR pore (measured via single-channel
      analysis of AChRs expressed in human embryonic kidney cells). PQ1-5 are
      comparable in pore-binding affinity to the strongest AChR open-channel blockers
      previously reported, which have complex molecular structures. These results
      suggest a general approach for designing potent open-channel blockers from a
      structurally flexible polymer. This design strategy involves simple synthetic
      procedures and does not require detailed information about the structure of an
      ion-channel pore. 

PMID- 25386751
TI  - SNaPshot assay for the detection of the most common CFTR mutations in infertile
      men.
AB  - Congenital bilateral absence of vas deferens (CBAVD) is the most common CFTR
      related disorder (CFTR-RD) that explains about 1-2% of the male infertility
      cases. Controversial data have been published regarding the involvement of CFTR
      mutations in infertile men with non-obstructive azoospermia and oligozoospermia.
      Here, we describe single base extension (SNaPshot) assay for detection of 11
      common CFTR mutations: F508del, G542X, N1303K, 621+1G->T, G551D, R553X, R1162X,
      W1282X, R117H, 2184insA and 1717-1G->A and IVS8polyT variants. The assay was
      validated on 50 previously genotyped samples and was used to screen a total of
      369 infertile men with different impairment of spermatogenesis and 136 fertile
      controls. Our results show that double heterozygosity of cystic fibrosis (CF) and
      CFTR-related disorder (CFTR-RD) mutations are found in a high percentage (22.7%)
      of infertile men with obstructive azoospermia, but not in other studied groups of
      infertile men. The SNaPshot assay described here is an inexpensive, fast and
      robust method for primary screening of the most common CFTR mutations both in
      patients with classical CF and CFTR-RD. It can contribute to better understanding
      of the role of CFTR mutations in impaired spermatogenesis, ultimately leading to
      improved management of infertile men. 

PMID- 25386752
TI  - Adductor canal block for postoperative pain treatment after revision knee
      arthroplasty: a blinded, randomized, placebo-controlled study.
AB  - BACKGROUND: Revision knee arthroplasty is assumed to be even more painful than
      primary knee arthroplasty and predominantly performed in chronic pain patients,
      which challenges postoperative pain treatment. We hypothesized that the adductor
      canal block, effective for pain relief after primary total knee arthroplasty, may
      reduce pain during knee flexion (primary endpoint: at 4 h) compared with placebo
      after revision total knee arthroplasty. Secondary endpoints were pain at rest,
      morphine consumption and morphine-related side effects. METHODS: We included
      patients scheduled for revision knee arthroplasty in general anesthesia into this
      blinded, placebo-controlled, randomized trial. Patients were allocated to an
      adductor canal block via a catheter with either ropivacaine or placebo; bolus of
      0.75% ropivacaine/saline, followed by infusion of 0.2% ropivacaine/saline.
      Clinicaltrials.gov ID: NCT01191593. RESULTS: We enrolled 36 patients, of which 30
      were analyzed. Mean pain scores during knee flexion at 4 h (primary endpoint)
      were: 52 +/- 22 versus 71 +/- 25 mm (mean difference 19, 95% CI: 1 to 37, P =
      0.04), ropivacaine and placebo group respectively. When calculated as area under
      the curve (1-8 h/7 h) pain scores were 55 +/- 21 versus 69 +/- 21 mm during knee
      flexion (P = 0.11) and 39 +/- 18 versus 45 +/- 23 mm at rest (P = 0.43),
      ropivacaine and placebo group respectively. Groups were similar regarding
      morphine consumption and morphine-related side effects (P > 0.05). CONCLUSIONS:
      The only statistically significant difference found between groups was in the
      primary endpoint: pain during knee flexion at 4 h. However, due to a larger than
      anticipated dropout rate and heterogeneous study population, the study was
      underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01191593.

PMID- 25386753
TI  - Influence of Asian dust particles on immune adjuvant effects and airway
      inflammation in asthma model mice.
AB  - OBJECTIVE: An Asian dust storm (ADS) contains airborne particles that affect
      conditions such as asthma, but the mechanism of exacerbation is unclear. The
      objective of this study was to compare immune adjuvant effects and airway
      inflammation induced by airborne particles collected on ADS days and the original
      ADS soil (CJ-1 soil) in asthma model mice. METHODS: Airborne particles were
      collected on ADS days in western Japan. NC/Nga mice were co-sensitized by
      intranasal instillation with ADS airborne particles and/or Dermatophagoides
      farinae (Df), and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized
      mice were stimulated with Df challenge intranasally at 7 days after the last Df
      sensitization. At 24 hours after challenge, serum allergen specific antibody,
      differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage
      fluid (BALF) were measured, and airway inflammation was examined
      histopathologically. RESULTS: Co-sensitization with ADS airborne particles and Df
      increased the neutrophil and eosinophil counts in BALF. Augmentation of airway
      inflammation was also observed in peribronchiolar and perivascular lung areas. Df
      specific serum IgE was significantly elevated by ADS airborne particles, but not
      by CJ-1 soil. Levels of interleukin (IL)-5, IL-13, IL-6, and macrophage
      inflammatory protein-2 were higher in BALF in mice treated with ADS airborne
      particles. CONCLUSION: These results suggest that substances attached to ADS
      airborne particles that are not in the original ADS soil may play important roles
      in immune adjuvant effects and airway inflammation.

PMID- 25386755
TI  - Visual Feedback of Bilateral Bite Force to Assess Motor Control of the Mandible
      in Isometric Condition.
AB  - The assessment of the individual ability of modulating and coordinating the right
      and left bite force is poorly investigated. The present study describes a
      methodology for the assessment of the bilateral control of the biting force and
      evaluates the test-retest reliability in a sample of 13 healthy subjects. By
      modulating the intensity and the left/right balance of the biting force, the
      subject was able to drive a cursor on the screen to "reach and hold" targets,
      randomly generated within the physiological "range of force" of the subject. The
      average motor performance was evaluated by the mean cursor-target distance = 13
      +/- 5%, the Offset Error = 9 +/- 5% and the standard deviation of the force
      vector = 17.7 +/- 6.1% (expressed as % of the target). Mean distance and standard
      deviation indices had acceptable reliability. This technique improves the
      characterization of the mandibular motor function and it may have a relevant role
      for the assessment and rehabilitation of the neuromusculoskeletal disorders
      affecting the orofacial system. 

PMID- 25386754
TI  - Diversity of microsporidia, Cryptosporidium and Giardia in mountain gorillas
      (Gorilla beringei beringei) in Volcanoes National Park, Rwanda.
AB  - BACKGROUND: Infectious diseases represent the greatest threats to endangered
      species, and transmission from humans to wildlife under increased anthropogenic
      pressure has been always stated as a major risk of habituation. AIMS: To evaluate
      the impact of close contact with humans on the occurrence of potentially zoonotic
      protists in great apes, one hundred mountain gorillas (Gorilla beringei beringei)
      from seven groups habituated either for tourism or for research in Volcanoes
      National Park, Rwanda were screened for the presence of microsporidia,
      Cryptosporidium spp. and Giardia spp. using molecular diagnostics. RESULTS: The
      most frequently detected parasites were Enterocytozoon bieneusi found in 18
      samples (including genotype EbpA, D, C, gorilla 2 and five novel genotypes
      gorilla 4-8) and Encephalitozoon cuniculi with genotype II being more prevalent
      (10 cases) compared to genotype I (1 case). Cryptosporidium muris (2 cases) and
      C. meleagridis (2 cases) were documented in great apes for the first time.
      Cryptosporidium sp. infections were identified only in research groups and
      occurrence of E. cuniculi in research groups was significantly higher in
      comparison to tourist groups. No difference in prevalence of E. bieneusi was
      observed between research and tourist groups. CONCLUSION: Although our data
      showed the presence and diversity of important opportunistic protists in
      Volcanoes gorillas, the source and the routes of the circulation remain unknown.
      Repeated individual sampling, broad sampling of other hosts sharing the habitat
      with gorillas and quantification of studied protists would be necessary to
      acquire more complex data.

PMID- 25386758
TI  - Heat flux sensors for infrared thermography in convective heat transfer.
AB  - This paper reviews the most dependable heat flux sensors, which can be used with
      InfraRed (IR) thermography to measure convective heat transfer coefficient
      distributions, and some of their applications performed by the authors' research
      group at the University of Naples Federico II. After recalling the basic
      principles that make IR thermography work, the various heat flux sensors to be
      used with it are presented and discussed, describing their capability to
      investigate complex thermo-fluid-dynamic flows. Several applications to streams,
      which range from natural convection to hypersonic flows, are also described. 

PMID- 25386756
TI  - Advantages and versatility of fluorescence-based methodology to characterize the
      functionality of LDLR and class mutation assignment.
AB  - Familial hypercholesterolemia (FH) is a common autosomal codominant disease with
      a frequency of 1:500 individuals in its heterozygous form. The genetic basis of
      FH is most commonly mutations within the LDLR gene. Assessing the pathogenicity
      of LDLR variants is particularly important to give a patient a definitive
      diagnosis of FH. Current studies of LDLR activity ex vivo are based on the
      analysis of 125I-labeled lipoproteins (reference method) or fluorescent-labelled
      LDL. The main purpose of this study was to compare the effectiveness of these two
      methods to assess LDLR functionality in order to validate a functional assay to
      analyse LDLR mutations. LDLR activity of different variants has been studied by
      flow cytometry using FITC-labelled LDL and compared with studies performed
      previously with 125I-labeled lipoproteins. Flow cytometry results are in full
      agreement with the data obtained by the 125I methodology. Additionally confocal
      microscopy allowed the assignment of different class mutation to the variants
      assayed. Use of fluorescence yielded similar results than 125I-labeled
      lipoproteins concerning LDLR activity determination, and also allows class
      mutation classification. The use of FITC-labelled LDL is easier in handling and
      disposal, cheaper than radioactivity and can be routinely performed by any group
      doing LDLR functional validations.

PMID- 25386759
TI  - Remote sensing of ecosystem health: opportunities, challenges, and future
      perspectives.
AB  - Maintaining a healthy ecosystem is essential for maximizing sustainable
      ecological services of the best quality to human beings. Ecological and
      conservation research has provided a strong scientific background on identifying
      ecological health indicators and correspondingly making effective conservation
      plans. At the same time, ecologists have asserted a strong need for spatially
      explicit and temporally effective ecosystem health assessments based on remote
      sensing data. Currently, remote sensing of ecosystem health is only based on one
      ecosystem attribute: vigor, organization, or resilience. However, an effective
      ecosystem health assessment should be a comprehensive and dynamic measurement of
      the three attributes. This paper reviews opportunities of remote sensing,
      including optical, radar, and LiDAR, for directly estimating indicators of the
      three ecosystem attributes, discusses the main challenges to develop a remote
      sensing-based spatially-explicit comprehensive ecosystem health system, and
      provides some future perspectives. The main challenges to develop a remote
      sensing-based spatially-explicit comprehensive ecosystem health system are: (1)
      scale issue; (2) transportability issue; (3) data availability; and (4)
      uncertainties in health indicators estimated from remote sensing data. However,
      the Radarsat-2 constellation, upcoming new optical sensors on Worldview-3 and
      Sentinel-2 satellites, and improved technologies for the acquisition and
      processing of hyperspectral, multi-angle optical, radar, and LiDAR data and multi
      sensoral data fusion may partly address the current challenges. 

PMID- 25386760
TI  - Thyrotropin suppression increases the risk of osteoporosis without decreasing
      recurrence in ATA low- and intermediate-risk patients with differentiated thyroid
      carcinoma.
AB  - BACKGROUND: Levothyroxine suppression of thyrotropin (TSH) is broadly applied to
      patients with thyroid cancer despite lack of consensus on the optimal TSH
      concentration necessary to reduce cancer recurrence while minimizing toxicity
      from subclinical hyperthyroidism. The objectives of this study were to examine
      the beneficial effects and the cardiac and skeletal toxicity of TSH suppression
      in well-differentiated thyroid carcinoma (DTC). METHODS: A total of 771 patients
      (569 women) at ATA low or intermediate risk of recurrence, with a mean age of
      48+/-14 years, and undergoing total thyroidectomy at a tertiary care center
      between 2000 and 2006 were followed for a median of six and a half years. They
      were divided into a suppressed TSH group (median TSH <=0.4 mIU/L) and a
      nonsuppressed group (median TSH >0.4 mIU/L). Structural recurrence of thyroid
      cancer, postoperative atrial fibrillation (AF), and osteoporosis were examined in
      the two groups. Osteoporosis was only examined in women. RESULTS: A total of
      43/771 (5.6%) patients recurred, 29/739 (3.9%) patients were diagnosed with
      postoperative osteoporosis, and 17/756 (2.3 %) were diagnosed with postoperative
      AF. Despite similar rates of recurrence (HR 1.02, p=0.956 [CI 0.54-1.91]),
      patients treated to a median TSH <=0.4 mIU/L were at increased postoperative risk
      of a composite outcome of AF and osteoporosis (HR 2.1, p=0.05 [CI 1.001-4.3])
      compared to those not suppressed. A differential risk of AF alone (HR 0.78,
      p=0.63 [CI 0.3-2.1]) was not detected, but postoperative osteoporosis was
      increased among women with a suppressed TSH compared to those not suppressed (HR
      3.5, p=0.023 [CI 1.2-10.2]). The increased risk of postoperative osteoporosis
      disappeared when the patient's median TSH was maintained around 1 mIU/L.
      CONCLUSION: TSH suppression significantly increases the risk of postoperative
      osteoporosis without changing tumor recurrence in ATA low- and intermediate-risk
      patients with DTC. Future interventions should focus on avoiding harm in indolent
      disease.

PMID- 25386761
TI  - Hepatitis B virus-associated glomerulonephritis in HBsAg serological-negative
      patients.
AB  - OBJECTIVE: The main objective of this study is to report the clinical and
      pathological characteristics of hepatitis B virus (HBV)-associated
      glomerulonephritis (HBV-GN) in serum hepatitis B surface antigen (HBsAg)-negative
      patients in China. HBV-GN is caused by the HBV's attack on the kidney tissues,
      but definitive diagnostic criteria are still lacking. The diagnostic criteria
      used in China require HBsAg positivity in the serum, but research on occult HBV
      infection has shown that HBV infection is also found in serum HBsAg-negative
      patients. Clinical and pathological characterization of HBV-GN in serum HBsAg
      negative patients is required. MATERIALS AND METHODS: Serologic and clinical
      findings and pathological characteristics of renal tissues in 18 HBV-GN patients
      (11 men and seven women) with serum HBsAg negativity were analyzed
      retrospectively. Thirty-three HBV-GN patients with serum HBsAg positivity and 59
      patients with membranous nephropathy (MN) without any HBV infection markers in
      serum and renal tissues during the same period were included as controls.
      RESULTS: Among the 18 HBsAg-negative patients with GN, 12 had HBsAb positivity in
      their sera. None of the patients was positive for serum HBeAg. Proteinuria was
      the major clinical manifestation and the renal histopathology was characterized
      as MN. Immune fluorescence deposits in renal tissues consisted mainly of HBsAg.
      The degree of renal injury and the decrease in the C3 level were less than those
      in HBsAg-positive patients and idiopathic membranous nephropathy patients.
      CONCLUSION: We propose to use the HBV marker in renal tissues as a new diagnostic
      criterion for HBV-GN. If MN patients have HBV marker positivity in renal tissues,
      HBV-GN can be diagnosed even without HBsAg in the serum. This would improve the
      diagnostic accuracy and potential treatment efficiency.

PMID- 25386762
TI  - Portal hypertensive gastropathy in cirrhotics without varices: a case-control
      study.
AB  - OBJECTIVE: Information is lacking on portal hypertensive gastropathy (PHG) in
      cirrhotics without varices; our aim it is to evaluate whether clinical and
      sonographic parameters are associated with PHG and may provide information
      suitable for the management of these patients. PATIENTS AND METHODS: After
      endoscopic selection of 145 cirrhotics without varices, 75 with PHG and 70
      without PHG, clinical and sonographic characteristics were assessed. RESULTS:
      Forty portosystemic shunts were present in 27 patients. The mean Child-Pugh score
      was 6.3+/-1.4 and 5.6+/-0.5 in patients with severe and mild PHG, respectively
      (P=0.004). The mean portal vein diameter was 10.4+/-1.7 and 11.6+/-2.0 mm in
      cirrhotics without and with PHG, respectively (P=0.0002). CONCLUSION: A link
      between the presence of PHG and a more advanced phase of cirrhosis was found.
      Duplex Doppler sonography was confirmed to be a valuable diagnostic method in
      monitoring cirrhosis. Management of these patients cannot be performed on the
      basis of a single diagnostic method, and a multimodal diagnostic approach is
      required.

PMID- 25386763
TI  - Anger expression styles in schizophrenia spectrum disorders: associations with
      anxiety, paranoia, emotion recognition, and trauma history.
AB  - Heightened levels of anger and dysregulated expression of anger have been
      associated with poorer outcomes and treatment response for persons with
      schizophrenia spectrum disorders. Less is known, however, about the psychological
      processes that determine the extent to which anger is expressed in a more versus
      less adaptive manner. To explore this issue, this study gathered reports of anger
      expression style in 88 persons with schizophrenia or schizoaffective disorder
      using the State-Trait Anger Expression Inventory, Second Edition. The authors
      additionally assessed anxiety, suspiciousness, emotion recognition, self-esteem,
      and cumulative trauma history. Correlations and multiple regression analyses
      showed that outward anger control, that is, the suppression of anger, was
      predicted by lower levels of suspiciousness, poorer emotion recognition, and
      reduced anxiety. Participants who endorsed greater anxiety and had experienced
      more traumatic events reported a heightened tendency to express anger both
      inwardly and outwardly. 

PMID- 25386764
TI  - Posttraumatic growth after earthquake trauma is predicted by executive functions:
      a pilot study.
AB  - Although positive personal change after adverse events (posttraumatic growth
      [PTG]) is repeatedly shown to occur after a range of traumatic or distressing
      events, there is still a debate on the validity of the concept. Using the
      objective measurement of cognitive functions, we attempted to show that PTG is a
      scientifically valid construct in a group of earthquake survivors. This is the
      first study to associate PTG with cognitive functioning. We found that growth was
      predicted by executive functions and not by memory or processing speed, showing
      that the correlation between cognitive functions and growth is a specific one. In
      addition, a specific form of PTG, namely personal growth, was related to
      cognitive functions, whereas relational growth was not. Our findings provide
      support for the validity of the PTG concept. 

PMID- 25386765
TI  - Measuring secondary traumatic stress symptoms in military spouses with the
      posttraumatic stress disorder checklist military version.
AB  - Little research to date has examined secondary traumatic stress symptoms in
      spouses of military veterans. This study investigated the presence and severity
      of posttraumatic stress symptoms in a sample of 227 Army National Guard veterans
      and secondary traumatic stress symptoms among their spouses. The veterans
      completed the posttraumatic stress disorder (PTSD) Checklist Military Version
      (PCL-M) (Weathers et al., 1993) to determine the probable prevalence rate of
      posttraumatic stress symptoms. A modified version of the PCL-M was used to assess
      secondary traumatic stress symptoms in the spouses. A confirmatory factor
      analysis showed that the modified version of the PCL-M used to assess secondary
      traumatic stress symptoms in spouses fits using the same four-factor PTSD
      structure as the PCL-M for veterans. This study provides initial evidence on the
      underlying symptom structure of secondary traumatic stress symptoms among spouses
      of traumatic event victims. 

PMID- 25386766
TI  - Studies on expression of p14ARF and MDM2 in human thyroid neoplasms.
AB  - AIM: We sought to evaluate the expression and clinical significance of p14ARF and
      MDM2 proteins in thyroid neoplasm. METHODS: Immunohistochemical streptavidin
      peroxidase (S-P) method was used to detect the expression of p14ARF and MDM2
      proteins in 78 cases of papillary thyroid carcinoma (PTC), 34 cases of papillary
      thyroid microcarcinoma (PTMC) and 45 cases of thyroid adenoma. RESULTS: The
      expression of p14ARF and MDM2 protein differed significantly (P<0.01) among three
      group. The positivity rate of p14ARF protein in PTC was significantly lower than
      that in thyroid adenoma (P=0.002) and PTMC (P=0.008). While the positivity rate
      of MDM2 protein in PTC was significantly higher than that in thyroid adenoma
      (P=0.000) and PTMC (P=0.009). There was a significant correlation found between
      the expressions of p14ARF and MDM2 proteins in PTC (P=0.013) and PTMC (P=0.012).
      Also, a significant correlation was found between p14ARF protein expression and
      lymph node metastasis in PTC (P=0.011). CONCLUSION: It was concluded that p14ARF
      and MDM2 proteins might be involved in the induction and development of PTC and
      PTMC whereas p14ARF also had diagnostic value in determining the biological
      behavior of PTC.

PMID- 25386767
TI  - An interferon-free antiviral regimen for HCV after liver transplantation.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is the leading indication for liver
      transplantation worldwide, and interferon-containing regimens are associated with
      low response rates owing to treatment-limiting toxic effects in immunosuppressed
      liver-transplant recipients. We evaluated the interferon-free regimen of the NS5A
      inhibitor ombitasvir coformulated with the ritonavir-boosted protease inhibitor
      ABT-450 (ABT-450/r), the nonnucleoside NS5B polymerase inhibitor dasabuvir, and
      ribavirin in liver-transplant recipients with recurrent HCV genotype 1 infection.
      METHODS: We enrolled 34 liver-transplant recipients with no fibrosis or mild
      fibrosis, who received ombitasvir-ABT-450/r (at a once-daily dose of 25 mg of
      ombitasvir, 150 mg of ABT-450, and 100 mg of ritonavir), dasabuvir (250 mg twice
      daily), and ribavirin for 24 weeks. Selection of the initial ribavirin dose and
      subsequent dose modifications for anemia were at the investigator's discretion.
      The primary efficacy end point was a sustained virologic response 12 weeks after
      the end of treatment. RESULTS: Of the 34 study participants, 33 had a sustained
      virologic response at post-treatment weeks 12 and 24, for a rate of 97% (95%
      confidence interval, 85 to 100). The most common adverse events were fatigue,
      headache, and cough. Five patients (15%) required erythropoietin; no patient
      required blood transfusion. One patient discontinued the study drugs owing to
      adverse events after week 18 but had a sustained virologic response. Blood levels
      of calcineurin inhibitors were monitored, and dosages were modified to maintain
      therapeutic levels; no episode of graft rejection was observed during the study.
      CONCLUSIONS: Treatment with the multitargeted regimen of ombitasvir-ABT-450/r and
      dasabuvir with ribavirin was associated with a low rate of serious adverse events
      and a high rate of sustained virologic response among liver-transplant recipients
      with recurrent HCV genotype 1 infection, a historically difficult-to-treat
      population. (Funded by AbbVie; CORAL-I ClinicalTrials.gov number, NCT01782495.).

PMID- 25386768
TI  - Design, synthesis, and biological activities of aromatic gossypol Schiff base
      derivatives.
AB  - A series of aromatic gossypol Schiff bases have been successfully synthesized via
      a feasible chemical modification. The antiviral activity against tobacco mosaic
      virus (TMV) of these gossypol Schiff bases has been tested for the first time.
      The bioassay studies indicated most of these derivatives exhibited excellent anti
      TMV activity, in which o-trifluoromethylaniline Schiff base (19) displayed the
      best antiviral activities. Furthermore, compound 19 exhibited an eminent anti-TMV
      effect in the field and low toxicity to mice. These results suggest it is a
      promising candidate for the inhibitor of plant virus. 

PMID- 25386769
TI  - Ligand-controlled, tunable silver-catalyzed C-H amination.
AB  - The development of readily tunable and regioselective C-H functionalization
      reactions that operate solely through catalyst control remains a challenge in
      modern organic synthesis. Herein, we report that simple silver catalysts
      supported by common nitrogenated ligands can be used to tune a nitrene transfer
      reaction between two different types of C-H bonds. The results reported herein
      represent the first example of ligand-controlled and site-selective silver
      promoted C-H amination. 

PMID- 25386771
TI  - Commentary on "Individual and societal wisdom: explaining the paradox of human
      aging and high well-being" by Dilip V. Jeste and Andrew J. Oswald: individual and
      societal wisdom in later life: the search for brain health.

PMID- 25386770
TI  - Individual and societal wisdom: explaining the paradox of human aging and high
      well-being.
AB  - OBJECTIVE: Although human aging is characterized by loss of fertility and
      progressive decline in physical abilities, later life is associated with better
      psychological health and well-being. Furthermore, there has been an unprecedented
      increase in average lifespan over the past century without corresponding
      extensions of fertile and healthy age spans. We propose a possible explanation
      for these paradoxical phenomena. METHOD: We reviewed the relevant literature on
      aging, well-being, and wisdom. RESULTS: An increase in specific components of
      individual wisdom in later life may make up for the loss of fertility as well as
      declining physical health. However, current data on the relationship between
      aging and individual wisdom are not consistent and do not explain increased
      longevity in the general population during the past century. We propose that
      greater societal wisdom (including compassion) may account for the notable
      increase in average lifespan over the last century. Data in older adults with
      serious mental illnesses are limited, but suggest that many of them too
      experience improved psychosocial functioning, although their longevity has not
      yet increased, suggesting persistent stigma against mental illness and inadequate
      societal compassion. CONCLUSIONS: The proposed construct of societal wisdom needs
      more investigation. Research should also focus on the reasons for discrepant
      findings related to age-associated changes in different components of individual
      wisdom. Studies of wisdom and well-being are warranted in older people with
      serious mental illnesses, along with campaigns to enhance societal compassion for
      these disenfranchised individuals. Finally, effective interventions to enhance
      wisdom need to be developed and tested.

PMID- 25386772
TI  - Commentary on "Individual and societal wisdom: explaining the paradox of human
      aging and high well-being" by Dilip V. Jeste and Andrew J. Oswald: societal
      wisdom and longevity.

PMID- 25386773
TI  - Commentary on "Individual and societal wisdom: explaining the paradox of human
      aging and high well-being" by Dilip V. Jeste and Andrew J. Oswald: as the years
      go by.

PMID- 25386774
TI  - Commentary on "Individual and societal wisdom: explaining the paradox of human
      aging and high well-being" by Dilip V. Jeste and Andrew J. Oswald: uncovering the
      genetic basis of well-being in older adults.

PMID- 25386775
TI  - Changing perceptions of illness in the early course of psychosis: psychological
      pathways to self-determination and self-management of treatment.
AB  - Treatment early in the course of psychosis can improve prognostic outcomes,
      facilitate adaptive functioning, and reduce familial and societal burden.
      However, little is known about the pathway of first episode psychosis (FEP) from
      the perspective of highly adherent adolescents and young adults. This study
      sought to understand the pathways in youth self-determination and self-management
      of treatment by investigating youth and parents' changing perceptions of illness
      in the early course of psychosis. Twenty-eight (n = 28) interviews were conducted
      using a semistructured interview guide on 12 adolescents following their FEP
      hospitalization and 16 parents. Standardized self-report forms and hospital
      inpatient records were used to collect and confirm demographic and clinical data.
      On average, three years had passed from initial hospitalization (age 16.2 years,
      SD = 1.2) to time of interview (age 19.3 years, SD = 2.3), thus allowing for a
      range of experiences across the early period of illness. Highly adherent
      adolescents experienced identifiable temporal phases of early psychosis,
      comprised of emergent and specific themes. Parents described a parallel pathway
      toward supporting their child's self-determination and self-management of
      treatments, with some distinct experiential differences. Five dominant themes
      that emerged across time were symptom recognition, awareness of change, negative
      appraisals, positive appraisals, and treatment self-management. Examining how
      these themes evolve over the early course of psychosis can help guide
      interventions that are compatible with the parent and adolescent's perceptions of
      illness at that point in time, and can therefore work in concert with the
      family's existing efforts to understand and manage their emerging condition and
      progress toward recovery. 

PMID- 25386776
TI  - Lifetime prevalence of and risk factors for suicidal ideation and suicide
      attempts in a Korean community sample.
AB  - OBJECTIVES: Our study evaluated the lifetime prevalence of and risk factors for
      suicidal ideation and suicide attempts in Jeollabuk-do Province, Korea. METHOD:
      Participants were selected from the population of individuals aged 13-100 years
      living Jeollabuk-do Province, Korea. A total of 2,964 subjects provided
      information about lifetime suicidal behavior and sociodemographic and
      psychological characteristics, completing the Zung Depression Scale, the Scale
      for Suicidal Ideation, the Multidimensional Anger Inventory, and the Rosenberg
      Self-Esteem Scale. RESULTS: The lifetime prevalence of suicidal ideation and
      suicide attempts, 24.8% and 6.2%, respectively, were higher than in previous
      studies. Multivariate regression revealed that family harmony had the highest
      odds ratio of all variables, including psychological factors. Along with
      depression and self-esteem, anger--which is the basic symptom of the Korean
      culture-related anger syndrome, Hwa-byung--was significantly associated with
      lifetime suicidal behavior. CONCLUSIONS: Lifetime suicidal behavior was highly
      prevalent in Jeollabuk-do Province. The most significant risk factors were found
      to be social support, family disharmony, anger, depression, and low self-esteem
      in Koreans.

PMID- 25386777
TI  - Previous exposure to the World Trade Center terrorist attack and posttraumatic
      symptoms among older adults following Hurricane Sandy.
AB  - OBJECTIVE: The present study tested the maturation and inoculation hypotheses by
      examining whether age and previous exposure to the September 11, 2001, World
      Trade Center (WTC) terrorist attack moderated the relationship between degree of
      exposure to Hurricane Sandy and related posttraumatic stress disorder (PTSD)
      symptoms. METHOD: An online sample of 1,000 participants from affected states
      completed self-report questionnaires one month after Hurricane Sandy hit the East
      Coast. Participants reported their degree of exposure to the WTC terrorist attack
      and to Hurricane Sandy, and their posttraumatic stress disorder (PTSD) symptoms
      following Hurricane Sandy. RESULTS: The positive relationship between degree of
      exposure to Hurricane Sandy and level of PTSD symptoms was weaker among older
      adults. An additional significant three-way interaction suggested that both age
      and previous exposure to the WTC terrorist attack moderated the relationship
      between degree of exposure to Hurricane Sandy and level of PTSD symptoms.
      Previous high degree of exposure to the WTC terrorist attack was related to a
      weaker effect of current exposure to Hurricane Sandy on PTSD symptoms among older
      adults. However, among younger adults, previous high degree of exposure to the
      WTC terrorist attack was related to a stronger effect of current exposure on PTSD
      symptoms. CONCLUSIONS: When confronted by a natural disaster, American older
      adults are generally resilient. Supporting the inoculation hypothesis, resilience
      of older adults may be partly related to the strength successfully extracted from
      previous exposure to adverse events.

PMID- 25386778
TI  - Exploring the longitudinal trajectories of posttraumatic stress disorder in
      injured trauma survivors.
AB  - OBJECTIVE: The goal of this study was to examine the longitudinal trajectories of
      posttraumatic stress disorder (PTSD) symptoms in a sample of acutely injured
      hospitalized civilian trauma survivors who participated in a randomized clinical
      trial. Prior longitudinal descriptive research has shown that there are distinct
      trajectories of PTSD symptoms over time in trauma survivors. Limited clinical
      trial research exists that describes the patterns of the trajectories as well as
      the risk factors that influence the trajectories for seriously injured trauma
      exposed patients. METHOD: Semiparametric, group-based approach trajectory
      modeling was used to examine four group trajectories of a subset of data obtained
      from a previous longitudinal clinical trial. Trajectories examined included
      resilience, recovery, relapsing/remitting, and chronic symptom patterns. One
      hundred and ninety-four patients who participated in the randomized clinical
      trial were assessed at baseline in the days and weeks after injury and then
      randomized. The associations between previously identified PTSD risk factors and
      the four trajectories were examined. RESULTS: The risk factors of ethnocultural
      minority status, psychiatric history, additional life stressors, and depressive
      symptoms, as well as intervention versus control group status, were found to
      significantly affect the probability of trajectory group membership for PTSD
      symptom severity. CONCLUSIONS: These findings suggest that there is a need for
      early PTSD interventions that anticipate differences in injured patients' PTSD
      trajectory profiles. Stepped care intervention procedures may optimally address
      the diverse PTSD trajectory patterns observed in injured trauma survivors through
      the tailoring of intervention timing and dosing.

PMID- 25386782
TI  - Robert W. Gibson, MD 1925-2014.

PMID- 25386784
TI  - Subtype-specific modulation of estrogen receptor-coactivator interaction by
      phosphorylation.
AB  - The estrogen receptor (ER) is the number one target for the treatment of
      endocrine responsive breast cancer and remains a highly attractive target for new
      drug development. Despite considerable efforts to understand the role of ER post
      translational modifications (PTMs), the complexity of these modifications and
      their impact, at the molecular level, are poorly understood. Using a chemical
      biology approach, fundamentally rooted in an efficient protein semisynthesis of
      tyrosine phosphorylated ER constructs, the complex role of the ER tyrosine
      phosphorylation is addressed here for the first time on a molecular level. The
      semisynthetic approach allows for the site-specific introduction of PTMs as well
      as biophysical probes. A combination of biophysical techniques, including NMR,
      with molecular dynamics studies reveals the role of the phosphorylation of the
      clinically relevant tyrosine 537 (Y537) in ERalpha and the analogous tyrosine
      (Y488) in ERbeta. Phosphorylation has important effects on the dynamics of the ER
      Helix 12, which is centrally involved in receptor activity regulation, and on its
      interplay with ligand and cofactor binding, but with differential regulatory
      effects of the analogous PTMs on the two ER subtypes. Combined, the results bring
      forward a novel molecular model of a phosphorylation-induced subtype specific ER
      modulatory mechanism, alternative to the widely accepted ligand-induced
      activation mechanism. 

PMID- 25386785
TI  - Molecular recognition and interaction between uracil and urea in solid-state
      studied by terahertz time-domain spectroscopy.
AB  - Using terahertz time-domain spectroscopy characterization, we observe that urea
      is able to recognize and interact with uracil efficiently even in the solid phase
      without involving water or solvents. A cocrystal configuration linked by a pair
      of hydrogen bonds between uracil and urea was formed. The terahertz absorption
      spectrum of the cocrystal shows a distinct new absorption at 0.8 THz (26.7 cm(
      1)), which originates from the intermolecular hydrogen bonding. Both mechanical
      milling and heating can accelerate the reaction efficiently. Density functional
      theory was adopted to simulate the vibrational modes of the cocrystal, and the
      results agree well with the experimental observation. Multiple techniques,
      including powder X-ray diffraction, scanning electron microscopy, and Fourier
      transform infrared spectroscopy, were performed to investigate the reaction
      process, and they presented supportive evidence. This work enables in-depth
      understanding of recognition and interaction of urea with nucleobases and
      comprehension of the denaturation related to RNA. We also demonstrate that
      terahertz spectroscopy is an effective and alternative tool for online
      measurement and quality control in pharmaceutical and chemical industries. 

PMID- 25386786
TI  - Oxidative nanopeeling chemistry-based synthesis and photodynamic and photothermal
      therapeutic applications of plasmonic core-petal nanostructures.
AB  - The precise control of plasmonic nanostructures and their use for less invasive
      apoptotic pathway-based therapeutics are important but challenging. Here, we
      introduce a highly controlled synthetic strategy for plasmonic core-petal
      nanoparticles (CPNs) with massively branched and plasmonically coupled
      nanostructures. The formation of CPNs was facilitated by the gold chloride
      induced oxidative disassembly and rupture of the polydopamine corona around Au
      nanoparticles and subsequent growth of Au nanopetals. We show that CPNs can act
      as multifunctional nanoprobes that induce dual photodynamic and photothermal
      therapeutic effects without a need for organic photosensitizers, coupled with the
      generation of reactive oxygen species (ROS), and allow for imaging and analyzing
      cells. Near-infrared laser-activated CPNs can optically monitor and efficiently
      kill cancer cells via apoptotic pathway by dual phototherapeutic effects and ROS
      mediated oxidative intracellular damage with a relatively mild increase in
      temperature, low laser power, and short laser exposure time. 

PMID- 25386787
TI  - Synthesis of gem-difluorinated nitroso compounds.
AB  - A method for the synthesis of gem-difluorinated nitroso compounds is described.
      The reaction involves interaction of organozinc reagents with
      (bromodifluoromethyl)trimethylsilane followed by nitrosation of difluorinated
      organozinc species with an n-butyl nitrite/chlorotrimethylsilane system. 

PMID- 25386788
TI  - Epstein-barr virus in gastric carcinoma.
AB  - The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases
      throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor
      the clonal EBV genome. Gastric carcinoma associated with EBV has distinct
      clinicopathological features, occurs predominately in men and in younger-aged
      individuals, and presents a generally diffuse histological type. Most cases of
      EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte
      infiltration. The immunological reactiveness in the host may represent a
      relatively preferable prognosis in EBV-positive cases. This fact highlights the
      important role of EBV in the development of EBV-associated gastric carcinoma. We
      have clearly proved direct infection of human gastric epithelialcells by EBV. The
      infection was achieved by using a recombinant EBV. Promotion of growth by EBV
      infection was observed in the cells. Considerable data suggest that EBV may
      directly contribute to the development of EBV-associated GC. This tumor-promoting
      effect seems to involve multiple mechanisms, because EBV affects several host
      proteins and pathways that normally promote apoptosis and regulate cell
      proliferation. 

PMID- 25386790
TI  - Phytoavailability of cadmium (Cd) to Pak choi (Brassica chinensis L.) grown in
      Chinese soils: a model to evaluate the impact of soil Cd pollution on potential
      dietary toxicity.
AB  - Food chain contamination by soil cadmium (Cd) through vegetable consumption poses
      a threat to human health. Therefore, an understanding is needed on the
      relationship between the phytoavailability of Cd in soils and its uptake in
      edible tissues of vegetables. The purpose of this study was to establish soil Cd
      thresholds of representative Chinese soils based on dietary toxicity to humans
      and develop a model to evaluate the phytoavailability of Cd to Pak choi (Brassica
      chinensis L.) based on soil properties. Mehlich-3 extractable Cd thresholds were
      more suitable for Stagnic Anthrosols, Calcareous, Ustic Cambosols, Typic
      Haplustalfs, Udic Ferrisols and Periudic Argosols with values of 0.30, 0.25,
      0.18, 0.16, 0.15 and 0.03 mg kg-1, respectively, while total Cd is adequate
      threshold for Mollisols with a value of 0.86 mg kg-1. A stepwise regression model
      indicated that Cd phytoavailability to Pak choi was significantly influenced by
      soil pH, organic matter, total Zinc and Cd concentrations in soil. Therefore,
      since Cd accumulation in Pak choi varied with soil characteristics, they should
      be considered while assessing the environmental quality of soils to ensure the
      hygienically safe food production. 

PMID- 25386792
TI  - The feasibility of utilizing pseudo CT-data for online MRI based treatment plan
      adaptation for a stereotactic radiotherapy treatment of spinal bone metastases.
AB  - The purpose of this study was to investigate what pseudo-CT (pCT) strategy is
      sufficient for online MRI based treatment plan adaptation of a stereotactic
      treatment for spinal bone metastases. For this purpose, the dosimetric accuracy
      of five increasingly complex pCT strategies was evaluated using the planning CT
      data of 20 patients suffering from spinal metastases. For each pCT, a treatment
      plan was developed and simulated on both the pCT and the original CT data of the
      patient. The two resulting dose distributions were compared using gamma analysis
      of 2%/2 mm. In this paper, a Gamma Pass Rate (GPR) of ? 95% within the Target
      Volume (TV) was considered clinically acceptable. We additionally demonstrated in
      this paper the automatic generation of each investigated pCT strategy with the
      use of dedicated MRI data complemented with pre-treatment CT data of a patient in
      treatment position. The dosimetric accuracy of a pCT increases when additional
      bulk densities are utilized for a pCT. However, the dosimetric accuracy of even
      the most complex 'bulk density' pCT strategy used in this study had an average
      GPR of only 78% within the TV. However, if information on the heterogeneous
      electron density distribution within the affected vertebral body was available, a
      clinically acceptable 99% mean GPR was observed. All pCTs could successfully be
      generated using the MRI data in combination with the CT data of a patient in
      treatment position. The results presented in this study show that a simple 'bulk
      density' pseudo-CT strategy is not feasible for online MRI based treatment plan
      adaptation for spinal bone metastases. However, a clinically acceptable result is
      generated if the information on the heterogeneous electron density (ED)
      distribution within the affected vertebral bone is available. Therefore, any pCT
      strategy for this tumor site should include a method which can estimate the
      heterogeneous ED of the affected vertebral bone.

PMID- 25386791
TI  - Growth hormone-regulated mRNAs and miRNAs in chicken hepatocytes.
AB  - Growth hormone (GH) is a key regulatory factor in animal growth, development and
      metabolism. Based on the expression level of the GH receptor, the chicken liver
      is a major target organ of GH, but the biological effects of GH on the chicken
      liver are not fully understood. In this work we identified mRNAs and miRNAs that
      are regulated by GH in primary hepatocytes from female chickens through RNA-seq,
      and analyzed the functional relevance of these mRNAs and miRNAs through GO
      enrichment analysis and miRNA target prediction. A total of 164 mRNAs were found
      to be differentially expressed between GH-treated and control chicken
      hepatocytes, of which 112 were up-regulated and 52 were down-regulated by GH. A
      total of 225 chicken miRNAs were identified by the RNA-Seq analysis. Among these
      miRNAs 16 were up-regulated and 1 miRNA was down-regulated by GH. The GH
      regulated mRNAs were mainly involved in growth and metabolism. Most of the GH
      upregulated or GH-downregulated miRNAs were predicted to target the GH
      downregulated or GH-upregulated mRNAs, respectively, involved in lipid
      metabolism. This study reveals that GH regulates the expression of many mRNAs
      involved in metabolism in female chicken hepatocytes, which suggests that GH
      plays an important role in regulating liver metabolism in female chickens. The
      results of this study also support the hypothesis that GH regulates lipid
      metabolism in chicken liver in part by regulating the expression of miRNAs that
      target the mRNAs involved in lipid metabolism. 

PMID- 25386793
TI  - New insights into thermal decomposition of polycyclic aromatic hydrocarbon
      oxyradicals.
AB  - Thermal decompositions of polycyclic aromatic hydrocarbon (PAH) oxyradicals on
      various surface sites including five-membered ring, free-edge, zigzag, and
      armchair have been systematically investigated by using ab initio density
      functional theory B3LYP/6-311+G(d,p) basis set. The calculation based on Huckel
      theory indicates that PAHs (3H-cydopenta[a]anthracene oxyradical) with
      oxyradicals on a five-membered ring site have high chemical reactivity. The rate
      coefficients of PAH oxyradical decomposition were evaluated by using Rice
      Ramsperger-Kassel-Marcus theory and solving the master equations in the
      temperature range of 1500-2500 K and the pressure range of 0.1-10 atm. The
      kinetic calculations revealed that the rate coefficients of PAH oxyradical
      decomposition are temperature-, pressure-, and surface site-dependent, and the
      oxyradical on a five-membered ring is easier to decompose than that on a six
      membered ring. Four-membered rings were found in decomposition of the five
      membered ring, and a new reaction channel of PAH evolution involving four
      membered rings is recommended. 

PMID- 25386796
TI  - Self, memory, and imagining the future in a case of psychogenic amnesia.
AB  - We report a case of psychogenic amnesia and examine the relationships between
      autobiographical memory impairment, the self, and ability to imagine the future.
      Case study JH, a 60-year-old male, experienced a 6-year period of pervasive
      psychogenic amnesia covering all life events from childhood to the age of 53. JH
      was tested during his amnesic period and again following hypnotherapy and the
      recovery of his memories. JH's amnesia corresponded with deficits in self
      knowledge and imagining the future. Results are discussed with reference to
      models of self and memory and processes involving remembering and imagining. 

PMID- 25386795
TI  - Factors that influence physician decision making for indeterminate pulmonary
      nodules.
AB  - RATIONALE: Pulmonologists frequently encounter indeterminate pulmonary nodules in
      practice, but it is unclear what clinical factors they rely on to guide the
      diagnostic evaluation. OBJECTIVES: To assess the current approach to the
      management of indeterminate pulmonary nodules and to determine the extent to
      which the addition of a hypothetical diagnostic blood test will influence
      clinical decision making. METHODS: Selected pulmonologists practicing in the
      United States were invited to participate in a conjoint exercise based on 20
      randomly generated cases of varying age, smoking history, and nodule size. Some
      cases included the result of a hypothetical blood test. Each respondent chose
      from among three diagnostic options for a patient: noninvasive monitoring (i.e.,
      serial CT or positron emission tomography scan), a minor procedure (i.e., biopsy
      or bronchoscopy), or a major procedure (i.e., video-assisted thorascopic surgery
      or thoracotomy). Multivariate logistic regression was used to assess the impact
      of the three risk factors and the diagnostic blood test on decision making.
      MEASUREMENTS AND MAIN RESULTS: Four hundred nineteen physicians participated
      (response rate, 10%). One hundred fifty-three physician surveys met predetermined
      criteria and were analyzed (4% of all invitees). A diagnostic procedure was
      recommended for 23% of 6-mm nodules, versus 54, 66, 77, and 84% of nodules 10,
      14, 18, and 22 mm, respectively (P < 0.001). Older age limited recommendations
      for invasive testing: 54% of 80-year-olds versus 61, 64, 63, and 61% of patients
      71, 62, 53, and 44 years of age, respectively (P < 0.001). In multivariate
      analyses, nodule size, smoking history, age, and the blood test each influenced
      decision making (P < 0.001). CONCLUSIONS: The pulmonologists who participated in
      this survey were more likely to proceed with invasive testing, instead of
      observation or additional imaging, as the size of the nodule increased. The use
      of a hypothetical blood test resulted in significant alterations in the decision
      to pursue invasive testing.

PMID- 25386797
TI  - Reevaluation of a clinical resource for assessment of delirium, dementia, and
      depression.
AB  - There is a perennial need to extend geriatrics knowledge and expertise to primary
      care providers to meet the unique needs of older patients. Reaching the target
      population of providers in an effective manner presents challenges for educators
      and evaluation of education programs. Gaps in a previous dissemination of an
      Assessment Guide for delirium, dementia, and depression were addressed through a
      multimodal strategy to reach a greater proportion of the intended audience,
      primary care clinicians, and to further evaluate the clinical impact of this
      learning resource. Sixty-five health care providers completed a forced choice
      online questionnaire. The majority of respondents were primary care providers
      (62.5%) who used the Assessment Guide in clinical activities such as patient
      assessment and patient education. Semistructured interviews with selected key
      informants (N = 16) provided examples of clinical impact such as improved
      diagnosis and changes in medication.

PMID- 25386798
TI  - Synthesis, crystal structures and two-photon absorption properties of
      triphenylamine cyanoacetic acid derivative and its organooxotin complexes.
AB  - Three novel organooxotin complexes (Z1, Z2 and Z3) were synthesized by reaction
      of L1 (2-cyano-3-(4-(diphenylamino)phenyl) acrylic acid) with n-Bu2SnO, Ph3Sn(OH)
      and nBu6Sn2O. The structures of the three complexes have been confirmed by single
      crystal X-ray diffraction analysis. The metal complex Z1 features a ladder
      framework while Z2 and Z3 show discrete structures. The UV-vis absorption, single
      photon excited fluorescence (SPEF) and two-photon excited fluorescence (2PEF) of
      the complexes have been systematically studied, suggesting that the three metal
      complexes have strong two-photon absorption (2PA) and large 2PA cross-sections.
      It is noteworthy that Z2 possesses an enhanced two-photon absorption, and Z3
      exhibits larger 2PA cross-section per molecular weight compared to L1. Finally,
      high anti-tumor activity of these three metal complexes has also been identified.

PMID- 25386799
TI  - Quantitative measurements of vibration amplitude using a contact-mode
      freestanding triboelectric nanogenerator.
AB  - A vibration sensor is usually designed to measure the vibration frequency but
      disregard the vibration amplitude, which is rather challenging to be quantified
      due to the requirement of linear response. Here, we show the application of
      triboelectric nanogenerator (TENG) as a self-powered tool for quantitative
      measurement of vibration amplitude based on an operation mode, the contact-mode
      freestanding triboelectric nanogenerator (CF-TENG). In this mode, the
      triboelectrically charged resonator can be agitated to vibrate between two
      stacked stationary electrodes. Under the working principle with a constant
      capacitance between two electrodes, the amplitudes of the electric signals are
      proportional to the vibration amplitude of the resonator (provided that the
      resonator plate is charged to saturation), which has been illuminated both
      theoretically and experimentally. Together with its capability in monitoring the
      vibration frequency, the CF-TENG appears as the triboelectrification-based active
      sensor that can give full quantitative information about a vibration. In
      addition, the CF-TENG is also demonstrated as a power source for electronic
      devices. 

PMID- 25386800
TI  - Description of the OXA-23 beta-lactamase gene located within Tn2007 in a clinical
      isolate of Acinetobacter baumannii from Spain.
AB  - A carbapenem-resistant Acinetobacter baumannii expressing blaOXA-23 was recovered
      from an intensive care unit patient in a third-level hospital from Spain. Genetic
      analysis showed the association of this carbapenemase with the transposon Tn2007
      located in a plasmid of 10 kb. The isolate was classified as ST-1. This strain
      has shown a potential ability to displace other endemic strains in the hospital
      and is the first reported identification of A. baumannii carrying blaOXA-23
      related to Tn2007 in Spain. 

PMID- 25386802
TI  - How carbon-friendly is nuclear energy? A hybrid MRIO-LCA model of a Spanish
      facility.
AB  - Spain faces the challenge of 80-95% greenhouse gas emissions reduction by 2050
      (European Energy Roadmap). As a possible first step to fulfill this objective,
      this paper presents a two-level analysis. First, we estimate the carbon footprint
      of a hypothetical nuclear facility in Spain. Using a hybrid multiregional input
      output model, to avoid truncation while diminishing sector aggregation problems
      and to improve environmental leakages estimations, we calculate the CO2
      equivalent emissions associated with the different phases of the nuclear life
      cycle--construction, fuel processing and operation and maintenance--taking into
      account the countries or regions where the emissions have been generated. Our
      results estimate a nuclear carbon footprint of 21.30 gCO2e/kWh, of which 89%
      comes from regions outside Spain. In some regions, the highest impacts are mostly
      direct (92%, 95%, and 92% of total carbon emissions in the U.S., France, and UK,
      respectively), meaning that these emissions are linked to the inputs directly
      required for nuclear energy production; in other regions, indirect emissions are
      higher (83% in China), which becomes relevant for policy measures. Second,
      through the analyses of different scenarios, we unravel and quantify how
      different assumptions that are often taken in the literature result in different
      carbon emissions.

PMID- 25386801
TI  - Assessment of a new web-based sexual concurrency measurement tool for men who
      have sex with men.
AB  - BACKGROUND: Men who have sex with men (MSM) are the most affected risk group in
      the United States' human immunodeficiency virus (HIV) epidemic. Sexual
      concurrency, the overlapping of partnerships in time, accelerates HIV
      transmission in populations and has been documented at high levels among MSM.
      However, concurrency is challenging to measure empirically and variations in
      assessment techniques used (primarily the date overlap and direct question
      approaches) and the outcomes derived from them have led to heterogeneity and
      questionable validity of estimates among MSM and other populations. OBJECTIVE:
      The aim was to evaluate a novel Web-based and interactive partnership-timing
      module designed for measuring concurrency among MSM, and to compare outcomes
      measured by the partnership-timing module to those of typical approaches in an
      online study of MSM. METHODS: In an online study of MSM aged >=18 years, we
      assessed concurrency by using the direct question method and by gathering the
      dates of first and last sex, with enhanced programming logic, for each reported
      partner in the previous 6 months. From these methods, we computed multiple
      concurrency cumulative prevalence outcomes: direct question, day resolution /
      date overlap, and month resolution / date overlap including both 1-month ties and
      excluding ties. We additionally computed variants of the UNAIDS point prevalence
      outcome. The partnership-timing module was also administered. It uses an
      interactive month resolution calendar to improve recall and follow-up questions
      to resolve temporal ambiguities, combines elements of the direct question and
      date overlap approaches. The agreement between the partnership-timing module and
      other concurrency outcomes was assessed with percent agreement, kappa statistic
      (kappa), and matched odds ratios at the individual, dyad, and triad levels of
      analysis. RESULTS: Among 2737 MSM who completed the partnership section of the
      partnership-timing module, 41.07% (1124/2737) of individuals had concurrent
      partners in the previous 6 months. The partnership-timing module had the highest
      degree of agreement with the direct question. Agreement was lower with date
      overlap outcomes (agreement range 79%-81%, kappa range .55-.59) and lowest with
      the UNAIDS outcome at 5 months before interview (65% agreement, kappa=.14, 95% CI
      .12-.16). All agreements declined after excluding individuals with 1 sex partner
      (always classified as not engaging in concurrency), although the highest
      agreement was still observed with the direct question technique (81% agreement,
      kappa=.59, 95% CI .55-.63). Similar patterns in agreement were observed with dyad
      and triad-level outcomes. CONCLUSIONS: The partnership-timing module showed
      strong concurrency detection ability and agreement with previous measures. These
      levels of agreement were greater than others have reported among previous
      measures. The partnership-timing module may be well suited to quantifying
      concurrency among MSM at multiple levels of analysis.

PMID- 25386806
TI  - Tumor heterogeneity-based resistance guides personalized cancer medicine.

PMID- 25386805
TI  - Effects of long-term feeding of the polyphenols resveratrol and kaempferol in
      obese mice.
AB  - The effect of the intake of antioxidant polyphenols such as resveratrol and
      others on survival and different parameters of life quality has been a matter of
      debate in the last years. We have studied here the effects of the polyphenols
      resveratrol and kaempferol added to the diet in a murine model undergoing long
      term hypercaloric diet. Using 50 mice for each condition, we have monitored
      weight, survival, biochemical parameters such as blood glucose, insulin,
      cholesterol, triglycerides and aspartate aminotransferase, neuromuscular
      coordination measured with the rotarod test and morphological aspect of stained
      sections of liver and heart histological samples. Our data show that mice fed
      since they are 3-months-old with hypercaloric diet supplemented with any of these
      polyphenols reduced their weight by about 5-7% with respect to the controls fed
      only with hypercaloric diet. We also observed that mice fed with any of the
      polyphenols had reduced levels of glucose, insulin and cholesterol, and better
      marks in the rotarod test, but only after 1 year of treatment, that is, during
      senescence. No effect was observed in the rest of the parameters studied.
      Furthermore, although treatment with hypercaloric diets induced large changes in
      the pattern of gene expression in liver, we found no significant changes in gene
      expression induced by the presence of any of the polyphenols. Thus, our data
      indicate that addition of resveratrol or kaempferol to mice food produces an
      initial decrease in weight in mice subjected to hypercaloric diet, but beneficial
      effects in other parameters such as blood glucose, insulin and cholesterol, and
      neuromuscular coordination, only appear after prolonged treatments. 

PMID- 25386807
TI  - Perspectives from the American Society of Clinical Oncology 2014 Conference:
      breast cancer highlights.

PMID- 25386808
TI  - Perspectives from American Society of Clinical Oncology: translational and
      clinical research highlights in breast and colorectal cancers.
AB  - 2014 ASCO Annual Meeting, Chicago, IL, USA, 28 May-3 June 2014. Advances in
      translational and clinical research have improved our understanding of breast and
      colorectal cancers, and have enabled remarkable progress in their treatment.
      These advances continue to be of paramount importance for breast and colorectal
      cancers. This report will describe and comment on the key messages from selected
      abstracts presented at the 50th American Society of Medical Oncology annual
      meeting that will impact clinical practice in the near future.

PMID- 25386809
TI  - Serous adenocarcinoma of the ovary diagnosed during ultrasound evaluation for
      fertility preservation.
AB  - Breast cancer is the most common malignant tumor in women of reproductive age,
      and fertility preservation counseling is now an integral part of the initial
      management of these patients. This article reports the case of a 33-year-old
      woman diagnosed with breast cancer and referred for oncofertility counseling
      before her treatment. Despite a previous negative cancer workup, a transvaginal
      ultrasound scan, performed for antral follicle count as part of the initial
      ovarian reserve assessment, revealed a synchronous ovarian adenocarcinoma. A
      BRCA1 mutation was confirmed weeks later. This report highlights the role of
      transvaginal ultrasound in the initial evaluation and reviews the risks
      associated with fertility preservation in breast cancer patients.

PMID- 25386810
TI  - Eribulin: a new-generation antimicrotubule agent in lung cancer therapy.
AB  - Microtubule antagonists are highly active agents for treatment of metastatic lung
      cancer, but can lead to significant toxicities and tumor resistance. Eribulin
      mesylate is a novel antimicrotubule agent that binds at a different site of the
      microtubule chain, and has been shown to be effective against many tumor types in
      several Phase II trials. Studies revealed many potential mechanisms beyond
      disruption of microtubule machinery that may be linked to its superior efficacy
      and less degree of toxicities. To date, only Phase III evidence to support
      eribulin use is in breast cancer, but the ongoing Phase III trial testing its
      efficacy in metastatic lung cancer against treatment of physician's choice will
      prove its merits in this setting.

PMID- 25386811
TI  - A Phase II trial of dosage escalation of sorafenib in Asian patients with
      metastatic renal cell carcinoma.
AB  - AIM: To investigate the role of sorafenib dosage escalation in Asian patients
      with metastatic renal cell carcinoma that had progressed after routine dosages.
      PATIENTS & METHODS: Sorafenib dosage escalation to 600 or 800 mg twice a day was
      offered to 41 patients with metastatic renal cell carcinoma who had progressed on
      normal dosages. Clinical outcome, toxicity and favorable clinical covariables for
      progression-free survival (PFS) were evaluated. RESULTS: The median PFS with
      dosage-escalated therapy was 7 months. Drug-related adverse events were
      tolerable. The pre-escalation Karnofsky performance status, serum calcium
      concentration, neutrophil/lymphocyte ratio, PFS and the highest toxicity grade at
      the routine dosage were associated with a longer PFS in the dosage-escalation
      period. CONCLUSION: Sorafenib dosage escalation was efficacious and tolerable in
      Asian patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (no. ChiCTR
      ONRC-12002088).

PMID- 25386812
TI  - Enhancing cancer care in areas of limited resources: our next steps.
AB  - In-depth knowledge of local conditions is necessary in order to enhance care in
      low- and middle-income countries. In this review we discuss: improving cancer
      diagnosis, optimizing patient management, increasing health awareness,
      prevention, early detection, eradication of causative infectious diseases and
      agents, tobacco control, healthy diets and lifestyles, availability of diagnostic
      methods, easy access to care, affordable costs, improving infrastructures,
      quality care measures, implementing and adapting guidelines, multidisciplinary
      management, supportive and survivorship care, research and optimization of
      medical school curriculum and training in oncology. Establishment of national
      cancer control plans by policy makers, physician societies, medical schools, and
      patient advocates is recommended. We will review evidence and controversies, and
      outline the next steps needed to prevent cancer and enhance care of cancer
      patients in LMICs.

PMID- 25386813
TI  - Therapeutic approaches in patients with newly diagnosed follicular lymphoma.
AB  - The prognosis of follicular lymphoma (FL) has significantly improved over the
      last decade, particularly following the introduction of the anti-CD20 monoclonal
      antibody rituximab, which has challenged the old concept of FL as an incurable
      disease. However, the decision whether to start treatment in a patient with
      advanced FL or adopt a watch-and-wait policy remains a subject of controversy.
      Furthermore, the optimal first-line treatment for FL remains a clinical challenge
      owing to the numerous different therapeutic options available. In this review,
      the authors focus on the initial management of patients with newly diagnosed FL,
      consider the different treatment options for every stage, paying special
      consideration to the therapeutic approaches for each clinical scenario, and
      discuss future directions.

PMID- 25386814
TI  - Risk of cardiovascular toxicities in patients with solid tumors treated with
      sorafenib: an updated systematic review and meta-analysis.
AB  - BACKGROUND: We performed a systematic review and meta-analysis of cardiovascular
      toxicities associated with sorafenib. PATIENTS & METHODS: Eligible studies
      included randomized Phase II and III trials of patients with solid tumors
      receiving daily sorafenib treatment that described the following events:
      hypertension, bleeding, venous thromboembolism, left ventricular dysfunction
      myocardial ischemia and cerebrovascular events. RESULTS: A total of 18 randomized
      clinical trials were considered eligible for the meta-analysis. Patients treated
      with sorafenib had a significantly increased risk of hypertension (relative risk
      [RR]: 2.93; 95% CI: 1.52-5.66), bleeding (RR: 2.42; 95% CI: 1.63-3.62) and left
      ventricular dysfunction (RR: 9.38; 95% CI: 1.24-71.22). The risk for venous
      thromboembolism, myocardial ischemia and cerebrovascular events was
      nonsignificant. Subgroup analyses showed that tumor type and treatment regimen
      had no effect on the RR of cardiovascular toxicities. CONCLUSION: Our meta
      analysis demonstrated that sorafenib is associated with a higher risk of
      developing all grade hypertension and bleeding compared with controls.

PMID- 25386815
TI  - Interaction between DNA/histone methyltransferases and their inhibitors.
AB  - Epigenetic research has recently become one of the hotspots in the field of
      bioscience and drug design. DNA methylation and histone methylation serve a
      critical function in influencing gene expression and genome function. The
      inhibition of DNA and histone methyltransferases (DNMTs and HMTs) is a promising
      approach for the therapeutic treatment of numerous diseases, including cancer.
      This work reviews the recent achievements in methyltransferase crystallographic
      structure resolution and bioactive inhibitor screening. We discuss the features
      of DNA and HMT structures, as well as the mechanism and structure-function
      relationship of transferase inhibitors, to elucidate how methyltransferase and
      inhibitor interactions occur both internally and externally. This study briefly
      reviews the biological function, as well as the inhibitor discovery and
      development, of DNA/histone methyltransferases. 

PMID- 25386816
TI  - Role of microRNAs in osteoblasts differentiation and bone disorders.
AB  - Advanced studies of single stranded endogenous ~22 nt microRNAs (miRNAs) have
      demonstrated their diverse biological functions including control of cell
      differentiation, cell cycle and pathological conditions. Recent studies suggest
      the potential application of miRNAs in stem cell engineering. miRNAs play a vital
      role as post-transcriptional regulators of gene expression which controls
      osteoblasts-mediated bone formation and osteoclasts related bone remodeling.
      Transcriptional and post-transcriptional mechanisms regulate the differentiation
      of osteoblasts and osteogenesis. The differentiation of osteoblasts is a key step
      in the development of skeletal muscles and it is involved in triggering the
      signaling pathways. Signaling pathways like TGF&#946;, BMP and Wnt are regulated
      by miRNAs which in turn, are shown to be associated with bone dynamics and bone
      disorders. This recap highlights the role of miRNAs in osteoblasts
      differentiation and emphasizes their potential therapeutic role in metabolic bone
      disorders. 

PMID- 25386817
TI  - Glucocorticoids in patients with rheumatic diseases: friends or enemies of bone?
AB  - Increased bone resorption and enhanced risk of osteoporotic fractures are often
      reported in patients with diseases having immune system involvement, mainly
      inflammatory rheumatic diseases, for which glucocorticoids are more often
      prescribed because of their powerful antinflammatory effects. Among secondary
      osteoporosis, glucocorticoid-induced osteoporosis is the most common and severe
      form, and up to now prolonged glucocorticoid therapy has been considered the most
      important osteoporotic risk factor in rheumatic patients. However, it is now
      clear that the pathogenesis of osteoporosis in inflammatory rheumatic diseases is
      mediated by several factors. In particular, new discoveries within
      osteoimmunology concerning the complex relationship between bone and immunity,
      suggest that inflammation itself, through proinflammatory and osteoclastogenic
      cytokine overexpression, promotes bone resorption leading to increased skeletal
      fragility. Therefore, by controlling systemic inflammation, it is also possible
      to reduce the loss of bone mass which accompanies rheumatic diseases. From this
      point of view, we critically revisit the effects of glucocorticoids on bone in
      rheumatic diseases, in which they should be seen not just as an enemy of the bone
      health but eventually as a potential therapeutic tool capable of reducing the
      risk of osteoporosis by controlling disease activity and inflammation.

PMID- 25386818
TI  - Microglial activation as a compelling target for treating acute traumatic brain
      injury.
AB  - Microglia and several inflammatory cytokines and neurotrophic growth factors are
      involved in traumatic brain injury (TBI). Tumor necrosis factor-alpha (TNF-alpha)
      can be released by microglia, astrocytes, and neurons. TNF-alpha has been
      reported to be both proneurogenic and antineurogenic, depending upon the model,
      method, and cell-derived region. There are two subtypes of microglia: M1 and M2.
      The former (or M1 subtype of non-phagocytic microglia) is able to secrete higher
      levels of TNF-alpha but lower levels of interleukin (IL)-10 (IL-10), an anti
      inflammatory cytokine. Both the proinflammatory and the pro-apoptotic function
      can also be promoted by activation of tumor necrosis factor-receptor 1 (TNF-R1).
      In contrast, M2 activation produces lower levels of TNF-alpha but higher levels
      of IL-10. Pro-growth and survival pathways can be promoted by the activation of
      TNFR2. During the acute stage of TBI, both M1 subtype of microglia and TNF-R1 are
      activated to cause higher levels of TNF-alpha but lower levels of IL-10, which
      lead to suppressed neurogenesis, neuronal loss and organ dysfunction (so-called
      microglial activation I). In contrast, activation of both M2 subtype of microglia
      and TNF-R2 is able to promote neurogenesis and tissue recovery (so-called
      microglial activation II). The severity of TBI depends upon the net effects
      between microglial activation I and microglial activation II. Indeed, by using
      rodent models of TBI, therapeutic evaluation studies reveal that several agents
      or strategies attenuate contused brain volume and neurological deficits by
      inhibiting microglial activation I but inducing microglial activation II. For
      example, etanercept therapy might attenuate contused brain volume and
      neurological deficits by inactivating the M1 subtype and TNF-R1 to reduce the
      microglial activation I response, but it might promote neurogenesis and
      functional recovery by activating the M2 subtype and TNF-R2. Therefore, based on
      microglial responses I and II, we conclude that future studies should focus on
      multiple therapeutic agents and strategies for optimal TBI therapy. 

PMID- 25386819
TI  - Targeting the NFkappaB signaling pathways for breast cancer prevention and
      therapy.
AB  - The activation of nuclear factor-kappaB (NFkappaB), a proinflammatory
      transcription factor, is a commonly observed phenomenon in breast cancer. It
      facilitates the development of a hormone-independent, invasive, high-grade, and
      late-stage tumor phenotype. Moreover, the commonly used cancer chemotherapy and
      radiotherapy approaches activate NFkappaB, leading to the development of invasive
      breast cancers that show resistance to chemotherapy, radiotherapy, and endocrine
      therapy. Inhibition of NFkappaB results in an increase in the sensitivity of
      cancer cells to the apoptotic effects of chemotherapeutic agents and radiation
      and restoring hormone sensitivity, which is correlated with increased disease
      free survival in patients with breast cancer. In this review article, we focus on
      the role of the NFkappaB signaling pathways in the development and progression of
      breast cancer and the validity of NFkappaB as a potential target for breast
      cancer prevention and therapy. We also discuss the recent findings that NFkappaB
      may have tumor suppressing activity in certain cancer types. Finally, this review
      also covers the state-of-the-art development of NFkappaB inhibitors for cancer
      therapy and prevention, the challenges in targeting validation, and pharmacology
      and toxicology evaluations of these agents from the bench to the bedside. 

PMID- 25386821
TI  - Oxidative stress and post-stroke depression: possible therapeutic role of
      polyphenols?
AB  - Post-stroke depression is a common neuropsychiatric affective disorder that may
      develop after a stroke event. In addition to abnormalities in the biogenic amine
      neurotransmitters and cytokine expression induced by stroke we will focus on the
      role of oxidative stress and hypothesize that polyphenols may be useful as
      therapeutics targets for the treatment of post-stroke depression. In this paper,
      we discuss the hypothesis that increased oxidative stress in cerebral tissues
      during ischemia is implicated in the pathogenesis of depressive-like symptoms
      following stroke. There is substantive evidence regarding the role of oxidative
      stress in the pathogenesis of both stroke and depression, which provides support
      to this hypothesis. Reactive oxygen species, generated during stroke, cause
      oxidative stress, lipid peroxidation, protein oxidation, and DNA damage in neural
      tissues. The resultant pathophysiological processes in the neural tissues could
      be considered a leading mechanism in the induction of post-stroke depression.
      Antioxidants including polyphenols therefore, may play an important role in the
      outcomes of ischemia and stroke, due to their ability to protect neurons against
      oxidative stress, to mitigate ischemic damage via inhibition of lipid
      peroxidation and ability to interact with the generation of nitric oxide from the
      vascular endothelium, and also to decrease inflammation. These data suggest that
      polyphenols may therefore be a useful new therapeutic target for the treatment of
      post-stroke depression. 

PMID- 25386822
TI  - Involvement of cysteine proteases in cancer.
AB  - The cysteine protease family members play important roles in various pivotal
      cellular processes. The difficulty in the analysis of the effects of cysteine
      protease aberrations in cancer comes as a result of the fact that they take part
      in complex proteolytic pathways. Nevertheless, there is a vast amount of data
      regarding the involvement of distinct members of this family in divergent types
      of cancer. Cysteine proteases assist migration and development of the disease, as
      well as increase the invasiveness of particular kinds of tumors. They are
      designated as both drug targets, as well as cancer susceptibility biomarkers.
      This implies that the abnormalities in their activity and expression patterns may
      be associated with the hallmarks of cancer. This review demonstrates that the
      influence of cysteine proteases on different mechanisms underlying cancer is
      undisputable. Thus, they are potent targets for future study and should be
      recognized as key players in the fight against cancer. 

PMID- 25386823
TI  - Cardio-vascular activity of catestatin: interlocking the puzzle pieces.
AB  - Catestatin (CST), the Chromogranin A (CgA)-derived cationic and hydrophobic
      peptide, firstly recognized as an endogenous inhibitor of catecholamine
      secretion, functions as a physiological brake of the adreno-sympathetic
      chromaffin system. Its wide spectrum of activities includes relevant multilevel
      cardiovascular and antihypertensive influences. At central systemic level, CST
      seems to modulate the autonomic cardiovascular control possibly acting on
      baroreceptor afferent fibers of the nucleus tractus solitarius. This, as well as
      clinical and experimental (CgA-KO mice) evidences point to an important role of
      CST in the determinism and prevention of essential hypertension. At organ level,
      CST exerts myocardial (negative inotropy and lusitropy) effects and potently
      vasodilates endothelin-1 (ET-1)-preconstricted coronaries through beta2
      adrenergic receptor (AR)-Gi/o protein-nitric oxide (NO)-cGMP signalling, while
      counterbalancing beta adrenergic (ISO) stimulation. The contractile myocardial
      effects have been deeply analysed in fish and amphibian hearts, highlighting
      finely diversified mechanisms of action. CST also acts as cardioprotective agent
      in both pre- and post-conditioning through NO-dependent mechanisms implicating
      the Reperfusion Injury Salvage Kinase (RISK) signalling and the activation of
      mitoKATP channels. The CST-elicited cardiotropic and coronarotropic influences,
      along with the recently discovered proangiogenic and regulatory effects in
      glucose and lipid metabolism, contribute to delineate an integrated and updated
      picture of the peptide which emerges as a pleiotropic hormone with a wide range
      of cytokine-like characteristics. The aim of this review is to interlock some
      older and more recent evidences which may help to better perceive the subtle
      links and differences among the puzzle pieces that still need to be deciphered. 

PMID- 25386824
TI  - Cyclin-dependent kinase-2 as a target for cancer therapy: progress in the
      development of CDK2 inhibitors as anti-cancer agents.
AB  - Cyclin-dependent kinase-2 (CDK2) is a member of protein kinase family. It plays
      an important role in regulating various events of eukaryotic cell division cycle.
      Accumulated evidences indicated that over expression of CDK2 should cause the
      abnormal regulation of cell-cycle, which would be directly associated with
      hyperproliferation in cancer cells. Therefore, CDK2 was regarded as a potentially
      therapeutic target for cancer therapy. Knowledge of crystallography and
      availability of X-ray crystal structure of CDK2 have enabled us to understand the
      mode of CDK2 inhibition, which facilitated the development of numerous CDK2
      inhibitors. Some of the CDK2 inhibitors were investigated clinically for their
      potential as anti-cancer agents. In this review, we present the structure,
      functions and activation of CDK2 by cyclin binding with special focus on recent
      advances in the development of different classes of CDK2 inhibitors. We also
      summarize different strategies to achieve subtype specificity either by targeting
      a binding pocket other than ATP, i.e. allosteric ligand binding site or by
      natural protein inhibitors capable to disrupt CDK2-cyclin complexes. It is
      possible to develop pharmacologically relevant cytotoxic agents by specifically
      inhibiting CDK2 activity with lesser toxicity than traditional chemotherapeutic
      agents. 

PMID- 25386820
TI  - Recent development of multifunctional agents as potential drug candidates for the
      treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder.
      The available therapy is limited to the symptomatic treatment and its efficacy
      remains unsatisfactory. In view of the prevalence and expected increase in the
      incidence of AD, the development of an effective therapy is crucial for public
      health. Due to the multifactorial aetiology of this disease, the multi-target
      directed ligand (MTDL) approach is a promising method in search for new drugs for
      AD. This review updates information on the development of multifunctional
      potential anti-AD agents published within the last three years. The majority of
      the recently reported structures are acetylcholinesterase inhibitors, often
      endowed with some additional properties. These properties enrich the
      pharmacological profile of the compounds giving hope for not only symptomatic but
      also causal treatment of the disease. Among these advantageous properties, the
      most often reported are an amyloid-beta antiaggregation activity, inhibition of
      beta-secretase and monoamine oxidase, an antioxidant and metal chelating
      activity, NOreleasing ability and interaction with cannabinoid, NMDA or histamine
      H3 receptors. The majority of novel molecules possess heterodimeric structures,
      able to interact with multiple targets by combining different pharmacophores,
      original or derived from natural products or existing therapeutics (tacrine,
      donepezil, galantamine, memantine). Among the described compounds, several seem
      to be promising drug candidates, while others may serve as a valuable inspiration
      in the search for new effective therapies for AD. 

PMID- 25386825
TI  - New antihypertensive drugs under development.
AB  - Hypertension is the most common cardiovascular disease and remains the most
      prevalent risk factor for cardiovascular diseases and a major cause of death
      worldwide. Despite the large number of antihypertensive drugs available, in the
      majority of patients blood pressure still remains not optimally controlled and
      persists at high risk of cardiovascular complications. The limitations of current
      therapies have stimulated the research and development of new classes of
      antihypertensive agents, with different mechanisms of action, that provide a
      better blood pressure control, greater protection against organ damage, better
      tolerability and more effective prevention of cardiovascular diseases. However,
      essential hypertension is a multifactorial and multigenic disorder, which means
      that various mechanisms contribute to a greater or lesser extent to increase BP.
      Recent advances in the understanding of the multiple and complex cellular
      signalling pathways that modulate vascular smooth muscle cell contraction and
      growth involved in the regulation of vascular tone and in hypertension-induced
      end-organ damage have provided valuable insight in identifying new therapeutic
      targets. This article reviews new antihypertensive drugs under development,
      focusing on their mechanisms of action and possible advantages compared with
      traditional drugs. 

PMID- 25386826
TI  - GABA(A) receptor subtype-selectivity of novel bicuculline derivatives.
AB  - GABA(A) receptors are the major inhibitory neurotransmitter receptors in the
      central nervous system and are targets of clinically important drugs modulating
      GABA induced ion flux by interacting with distinct allosteric binding sites. ROD
      185 is a previously investigated structural analogue of the GABA site antagonist
      bicuculline, and a positive allosteric modulator acting via the benzodiazepine
      binding site. Here, we investigated 13 newly synthesized structural analogues of
      ROD 185 for their interaction with rat GABA(A) receptors. Using
      [(3)H]flunitrazepam binding assays, we identified four compounds exhibiting a
      higher affinity for the benzodiazepine binding site than ROD 185. Two electrode
      voltage clamp electrophysiology at recombinant GABA(A) receptors indicated that
      most of these compounds positively modulated GABA-induced currents at these
      receptors. Additionally, these experiments revealed that this compound class not
      only interacts with the benzodiazepine binding site at alphabetagamma receptors
      but also with a novel, so far unidentified binding site present in alphabeta
      receptors. Compounds with a high affinity for the benzodiazepine binding site
      stimulated GABA-induced currents stronger at alphabetagamma than at alphabeta
      receptors and preferred alpha3beta3gamma2 receptors. Compounds showing equal or
      smaller effects at alphabetagamma compared to alphabeta receptors differentially
      interacted with various alphabeta or alphabetagamma receptor subtypes.
      Surprisingly, five of these compounds interacting with alphabeta receptors showed
      a strong stimulation at alpha6beta3gamma2 receptors. The absence of any direct
      effects at GABA(A) receptors, as well as their potential selectivity for receptor
      subtypes not being addressed by benzodiazepines, make this compound class to a
      starting point for the development of drugs with a possible clinical importance.

PMID- 25386827
TI  - Polymers and formulation strategies of nanofibrous systems for drug delivery
      application and tissue engineering.
AB  - During the last decade, the formulation of nanofibrous materials loaded with
      different drugs for biomedical applications has evoked considerable interest. The
      large specific surface area, the special micro- and macrostructure of fiber mats,
      the possibility for gradual release and site-specific local delivery of the
      active compounds lead to cytotoxicity decrease and enhancement of the therapeutic
      effect of drugs and implants. The present review details the different spinning
      techniques applied for the design of micro- and nanofibrous drug delivery
      systems. It furthermore deals with the use of various polymers that are capable
      for the formation of fiber scaffolds of various biomedical applications. 

PMID- 25386828
TI  - Evaluating the coupling between foot pronation and tibial internal rotation
      continuously using vector coding.
AB  - Excessive pronation, because of its coupling with tibial internal rotation (TIR),
      has been implicated as a risk factor in the development of anterior knee pain
      (AKP). Traditionally, this coupling has been expressed as a ratio between the
      eversion range of motion and the TIR range of motion (Ev/TIR) that occurs during
      stance. Currently, this technique has not been used to evaluate specific injuries
      or the effects of sex. In addition, Ev/TIR is incapable of detecting coupling
      changes that occur throughout stance. Therefore, the purpose of this study was to
      compare the coupling between eversion and TIR in runners with (n = 19) and
      without AKP (n = 17) and across sex using the Ev/TIR ratio, and more continuously
      using vector coding. When using vector coding, significant coupling differences
      were noted in runners with AKP (34% to 38% stance), with runners with AKP showing
      relatively more TIR than eversion. Similarly significant differences were noted
      across sex (14%-25% and 36%-47% stance), with males transitioning from a loading
      to propulsive coordination pattern using a proximal to distal strategy, and
      female runners using a distal to proximal strategy. These differences were only
      detected when evaluating this coupling relationship using a continuous technique
      such as vector coding. 

PMID- 25386829
TI  - Spot Urine Concentrations Should Not be Used for Hydration Assessment: A
      Methodology Review.
AB  - A common practice in sports science is to assess hydration status using the
      concentration of a single spot urine collection taken at any time of day for
      comparison against concentration (specific gravity, osmolality, color) thresholds
      established from first morning voids. There is strong evidence that this practice
      can be confounded by fluid intake, diet, and exercise, among other factors,
      leading to false positive/negative assessments. Thus, the purpose of this paper
      is to provide a simple explanation as to why this practice leads to erroneous
      conclusions and should be curtailed in favor of consensus hydration assessment
      recommendations. 

PMID- 25386830
TI  - Targeting bone and fat with novel exercise for peripubertal boys: the CAPO kids
      trial.
AB  - Our goal was to test the effect of a brief, novel bone- and fat-targeted exercise
      program on bone, muscle, and fat in healthy pre and peripubertal boys. We
      conducted a 10-min, 3/wk capoeira and jumping exercise intervention for 9 months
      with year 5 and 6 school boys. Anthropometrics, maturity, heart rate, blood
      pressure, maximal vertical jump, aerobic capacity and calcaneal broadband
      ultrasound attenuation and stiffness index (BUA and SI; Achilles, GE) were
      assessed. Bone, lean and fat tissue (DXA; XR800, Norland), and parameters of bone
      geometry (pQCT, XCT3000, Stratec) were measured from a subsample of 36 boys. Of
      188 boys (10.6 +/- 0.5 yr) who consented, 172 completed all testing; 104
      exercisers (EX) and 68 controls (CON). 30 EX and 6 CON participants underwent DXA
      and pQCT measures. EX improved BUA (+4.3% vs. +2.1%, p = .035), waist
      circumference (+2.8% vs. +6.2%, p = .001), heart rate (-5.3% vs. +1.5%, p =
      .005), maximal vertical jump (+12.2% vs. -0.3%, p = .001) and estimated maximal
      oxygen consumption (+9.1% vs. +1.2%, p = .001) compared with CON. Three 10-min
      sessions of capoeira and jumping per week improved calcaneal bone and metabolic
      health of pre and peripubertal boys over the course of a school year with little
      disruption to the academic schedule. 

PMID- 25386831
TI  - Engagement in outpatient care for persons living with HIV in the United States.
AB  - Prior studies that have assessed engagement within the various stages of care for
      persons living with HIV (PLWH) studied patients receiving care in HIV medical
      care facilities. These data are not representative of care received throughout
      the United States, as not all PLWH receive care in HIV clinics. This study
      evaluated engagement in outpatient care and healthcare utilization for PLWH,
      beyond facilities that specialize in HIV. Cross-sectional data were from the 2009
      2010 National Hospital Ambulatory Medical Care Survey. Levels of care included
      receiving any care, receiving HIV-related care, established in care, engaged in
      care, and prescribed antiretroviral therapy (ARV). Factors associated with ARV
      prescription were determined by logistic regression. We analyzed data for ~2.6
      million outpatient clinic visits for PLWH. Of these, 90% were receiving HIV
      related care, 86% were established in care, 75% were engaged in care, and 65%
      were prescribed ARV. In stratified analysis, the proportion of PWLH who were
      engaged in care varied by race/ethnicity (p<0.001) and ARV prescription varied
      significantly across the three age groups (p=0.004). Clinic visits within the
      past year did not differ for those prescribed ARV vs. not prescribed ARV [median,
      IQR=3.3 visits (1.8-5.6) vs. 3.6 visits (1.3-5.9); p=0.7]. Seeing a physician was
      associated with ARV prescription (OR=0.27, 95% CI=0.15-0.51), whereas routine
      engagement in care was not associated with ARV prescription (OR=0.99, 95% CI=0.96
      1.03). Given that non-ARV-treated PLWH utilized outpatient care services at rates
      similar to ARV-treated PLWH, these routine clinic visits are missed opportunities
      for increasing ARV prescription in untreated patients.

PMID- 25386833
TI  - Recent advances in cell replacement therapies for the treatment of type 1
      diabetes.
AB  - Exogenous insulin administration is currently the only treatment available to all
      type 1 diabetes patients, but it is not a cure. By helping to regulate
      circulating blood glucose levels, it has significantly improved life expectancy,
      but there are still long-term complications associated with the disease that may
      be preventable with a treatment strategy that can provide better glycemic
      control. Isolated islet (or whole pancreas) transplantation, xenotransplantation,
      and the transplant of human pluripotent stem cell-derived beta-cells provide the
      potential to restore endogenous insulin production and reestablish normoglycemia.
      Here, we discuss the latest advances in these fields, including the use of
      encapsulation technology, as well as some of the hurdles that still need to be
      overcome for these alternative therapies to become mainstream and/or progress to
      clinical development.

PMID- 25386832
TI  - Mitigating or exacerbating effects of maternal-fetal programming of female mice
      through the food choice environment.
AB  - Humans live, eat, and become overweight/obese in complex surroundings where there
      are many available food choices. Prenatal exposure to poor food choices
      predisposes offspring to increased negative health risks, including obesity. Many
      animal experiments have analyzed intergenerational body weight parameters in an
      environment without food choices, which may not be directly translatable to the
      human food environment. In this study, offspring from mothers with a defined high
      fat diet (HFD) or low-fat diet (LFD) were arbitrarily assigned to either an
      exclusively LFD or HFD or to a diet where they have a choice between LFD and HFD
      (choice diet). Offspring displayed negative outcomes of increased body weight,
      body fat, serum leptin, and blood glucose levels when given the choice diet
      compared with offspring on the LFD. Conversely, improved energy expenditure was
      found for offspring given the choice diet compared with offspring from HFD dams
      given LFD. In addition, maternal diet-specific influences on offspring metabolic
      parameters were identified, especially in offspring from HFD dams, including
      positive outcomes of reduced leptin in LFD offspring, reduced corticosterone and
      cholesterol levels in HFD offspring, and increased exercise levels in choice
      offspring, as well as the negative outcome of increased calorie intake in LFD
      offspring from HFD dams. This defined model can now be used as the basis for
      future studies to characterize the cycle of inter- and intragenerational obesity
      and whether more realistic diet environments, especially those including choice,
      can mitigate phenotype.

PMID- 25386834
TI  - SiO and CH3OH mega-masers in NGC 1068.
AB  - Maser is an acronym for microwave amplification by stimulated emission of
      radiation; in astronomy mega-masers are masers in galaxies that are >= 10(6)
      times more luminous than typical galactic maser sources. Observational studies of
      mega-masers can help us to understand their origins and characteristics. More
      importantly, mega-masers can be used as diagnostic tracers to probe the physical
      properties of their parent galaxies. Since the late 1970s, only three types of
      molecules have been found to form mega-masers: H2O, OH and H2CO. Here we report
      the detection of both SiO and CH3OH mega-masers near the centre of Seyfert 2
      galaxy NGC 1068 at millimetre wavelengths, obtained using the IRAM 30-m
      telescope. We argue that the SiO mega-maser originated from the nuclear disk and
      the CH3OH mega-maser originated from shock fronts. High-resolution observations
      in the future will enable us to investigate AGN feedback and determine the masses
      of central supermassive black holes in such galaxies.

PMID- 25386835
TI  - Analytical Transmission Electron Microscopy of Amphibole Fibers From the Lungs of
      Quebec Miners.
AB  - The objective of this study is to describe the morphology, molecular structure,
      and chemistry of amphibole fibers from lung samples from workers in the
      chrysotile mines at Asbestos and Thetford Mines, Quebec. A fibrous tremolite
      actinolite contaminant in an asbestos ore sample from the deposit at Asbestos was
      used for comparison. Lattice imaging was performed using high-resolution
      transmission electron microscopy (HRTEM). Silica-rich amorphous coatings (SIRA)
      that may be related to carcinogenesis are noted on all of the HRTEM photographs
      of fibers retained in lung, but not on fiber surfaces of the bulk comparison
      sample. Fibers found in lung samples and in a bulk comparison sample are produced
      primarily by splitting of thicker crystals and, as such, might not be considered
      asbestos fibers on the basis of certain mineralogical criteria. Implications of
      SIRA coatings with respect to carcinogenesis are worthy of further study. 

PMID- 25386836
TI  - Fluid overload, pulse wave velocity, and ratio of brachial pre-ejection period to
      ejection time in diabetic and non-diabetic chronic kidney disease.
AB  - Fluid overload is one of the characteristics in chronic kidney disease (CKD).
      Changes in extracellular fluid volume are associated with progression of diabetic
      nephropathy. Not only diabetes but also fluid overload is associated with
      cardiovascular risk factors The aim of the study was to assess the interaction
      between fluid overload, diabetes, and cardiovascular risk factors, including
      arterial stiffness and left ventricular function in 480 patients with stages 4-5
      CKD. Fluid status was determined by bioimpedance spectroscopy method, Body
      Composition Monitor. Brachial-ankle pulse wave velocity (baPWV), as a good
      parameter of arterial stiffness, and brachial pre-ejection period (bPEP)/brachial
      ejection time (bET), correlated with impaired left ventricular function were
      measured by ankle-brachial index (ABI)-form device. Of all patients, 207 (43.9%)
      were diabetic and 240 (50%) had fluid overload. For non-diabetic CKD, fluid
      overload was associated with being female (beta = -2.87, P = 0.003), heart
      disease (beta = 2.69, P = 0.04), high baPWV (beta = 0.27, P = 0.04), low
      hemoglobin (beta = -1.10, P < 0.001), and low serum albumin (beta = -5.21, P <
      0.001) in multivariate analysis. For diabetic CKD, fluid overload was associated
      with diuretics use (beta = 3.69, P = 0.003), high mean arterial pressure (beta =
      0.14, P = 0.01), low bPEP/ET (beta = -0.19, P = 0.03), low hemoglobin (beta = 
      1.55, P = 0.001), and low serum albumin (beta = -9.46, P < 0.001). In conclusion,
      baPWV is associated with fluid overload in non-diabetic CKD and bPEP/bET is
      associated with fluid overload in diabetic CKD. Early and accurate assessment of
      these associated cardiovascular risk factors may improve the effects of entire
      care in late CKD.

PMID- 25386837
TI  - Absence of spatial tuning in the orbitofrontal cortex.
AB  - There is limited data in the literature to explicitly support the notion that
      neurons in OFC are truly action-independent in their coding. We set out to
      specifically test the hypothesis that OFC value-related neurons in area 13 m of
      the monkey do not carry information about the action required to obtain that
      reward--that activity in this area represents reward values in an abstract and
      action-independent manner. To accomplish that goal we had two monkeys select and
      execute saccadic eye movements to 81 locations in the visual field for three
      different kinds of juice rewards. Our detailed analysis of the response fields
      indicates that these neurons are insensitive to the amplitude or direction of the
      saccade required to obtain these rewards. Our data thus validate earlier
      proposals that neurons of 13 m in the OFC encode subjective value independent of
      the saccadic action required to obtain that reward.

PMID- 25386838
TI  - Initial experiences of a minimally invasive autopsy service. A report of the
      techniques and observations in the first 11 cases.
AB  - Our goal was to set up a clinical service for minimally invasive postmortem
      examination for the fetal and neonatal age group. The minimally invasive service
      consisted of imaging, external review, placental examination, and ancillary tests
      that form part of the formal autopsy process. Eleven patients had imaging and
      relevant conditions at death successfully determined with the minimally invasive
      service. We conclude that a minimally invasive autopsy service for fetal and
      neonatal cases is possible and acceptable to patients and professionals. 

PMID- 25386839
TI  - Cyanidin 3-O-beta-D-Glucoside Improves Bone Indices.
AB  - Oxidative stress (OS) promotes bone loss after menopause, and there is evidence
      that dietary antioxidants may reduce the level of OS in vivo. This study examined
      dose-dependent effects of blackberries (BBs) containing mainly cyanidin 3-O-beta
      d-glucoside (C3G) in preventing bone loss in an ovariectomized (Ovx) rat model.
      Nine-month-old female (N=38) Sprague-Dawley rats were scanned using dual-energy X
      ray absorptiometry for baseline whole body, bone mineral content (BMC), and bone
      mineral density (BMD). One group was sham operated (Sham) and three groups were
      ovariectomized (Ovx). The groups and corresponding diets were Sham+control diet
      (n=12), Ovx+control diet (n=12), Ovx+5% BB (n=7), and Ovx+10% BB (n=7). Control
      diet was AIN-93M rodent diet, and the Ovx+5% BB and Ovx+10% BB were a diet
      modified to contain powdered, freeze-dried BB at levels of 5% and 10% (w/w).
      Following 100 days of treatment, whole body BMC and BMD were reassessed and bone
      specimens, blood, and 24-h urine samples were collected for analyses. Findings
      indicate that ovariectomy (Ovx) compromised whole body BMC and trabecular
      microarchitecture of the proximal tibia and fourth lumbar vertebra. C3G-rich BB
      at the level of 5% modestly protected BMDs, loss of the tibia, lumbar vertebra,
      and femur by 2.4%, 2.7%, and 4.3% (P<.0013; .0437; .0004), respectively. BB 5%
      treatment significantly prevented loss of tibial trabecular bone volume and
      trabecular number by 37% and 21%, respectively (P<.05), and also significantly
      prevented tibial trabecular separation by 22%. We conclude that C3G-rich BB
      treatment at the level of 5% (w/w) but not at 10% (w/w) may modestly reduce Ovx
      induced bone loss evident by improved tibial, vertebral, and femoral BMD values,
      and tibial bone microstructural parameters. Bone protective effects may be as a
      result of the synergistic effects of phenolic compounds; however, further work is
      required to determine BBs' specific mechanisms of action. 

PMID- 25386841
TI  - Paracellular calcium transport across renal and intestinal epithelia.
AB  - Calcium (Ca(2+)) is a key constituent in a myriad of physiological processes from
      intracellular signalling to the mineralization of bone. As a consequence, Ca(2+)
      is maintained within narrow limits when circulating in plasma. This is
      accomplished via regulated interplay between intestinal absorption, renal tubular
      reabsorption, and exchange with bone. Many studies have focused on the highly
      regulated active transcellular transport pathways for Ca(2+) from the duodenum of
      the intestine and the distal nephron of the kidney. However, comparatively little
      work has examined the molecular constituents creating the paracellular shunt
      across intestinal and renal epithelium, the transport pathway responsible for the
      majority of transepithelial Ca(2+) flux. More specifically, passive paracellular
      Ca(2+) absorption occurs across the majority of the intestine in addition to the
      renal proximal tubule and thick ascending limb of Henle's loop. Importantly,
      recent studies demonstrated that Ca(2+) transport through the paracellular shunt
      is significantly regulated. Therefore, we have summarized the evidence for
      different modes of paracellular Ca(2+) flux across renal and intestinal epithelia
      and highlighted recent molecular insights into both the mechanism of secondarily
      active paracellular Ca(2+) movement and the identity of claudins that permit the
      passage of Ca(2+) through the tight junction of these epithelia. 

PMID- 25386842
TI  - New insights into ADAMs regulation of the GRO-alpha/CXCR2 system: focus on
      Sjogren's syndrome.
AB  - Chemokine-dependent signaling in immune cells is a very important mechanism
      leading to integrin activation and leukocyte recruitment. During the last years,
      several studies were performed investigating the role of the chemokine Growth
      related oncogene-alpha (GRO-alpha) and its receptor CXC chemokine receptor 2
      (CXCR2) in different diseases. Recently, many new functions and properties of GRO
      alpha/CXCR2 system have been discovered and associated with atherosclerosis,
      angiogenesis, and many inflammatory conditions, such as autoimmune diseases. The
      purpose of this review is to discuss current advances in our understanding of the
      function of the GRO-alpha/CXCR2 system and related clinical implications
      associated with autoimmune diseases, such as primary Sjogren's syndrome (pSjS).
      Included is a discussion of the role of the ADAM17 metalloproteinase in
      modulating the GRO-alpha/CXCR2 axis in pSjS. Notably inhibitors of ADAM17 are
      being developed for the treatment of various autoimmune diseases. We hope to
      further evaluate this system in the pathogenesis of autoimmune diseases to
      promote a background for therapeutic interventions. 

PMID- 25386843
TI  - Apple latent spherical virus vector as vaccine for the prevention and treatment
      of mosaic diseases in pea, broad bean, and eustoma plants by bean yellow mosaic
      virus.
AB  - We investigated the protective effects of a viral vector based on an Apple latent
      spherical virus (ALSV) harboring a segment of the Bean yellow mosaic virus (BYMV)
      genome against mosaic diseases in pea, broad bean, and eustoma plants caused by
      BYMV infection. In pea plants pre-inoculated with the ALSV vaccine and challenge
      inoculated with BYMV expressing green fluorescence protein, BYMV multiplication
      occurred in inoculated leaves, but was markedly inhibited in the upper leaves. No
      mosaic symptoms due to BYMV infection were observed in the challenged plants pre
      inoculated with the ALSV vaccine. Simultaneous inoculation with the ALSV vaccine
      and BYMV also prevented mosaic symptoms in broad bean and eustoma plants, and
      BYMV accumulation was strongly inhibited in the upper leaves of plants treated
      with the ALSV vaccine. Pea and eustoma plants were pre-inoculated with BYMV
      followed by inoculation with the ALSV vaccine to investigate the curative effects
      of the ALSV vaccine. In both plant species, recovery from mosaic symptoms was
      observed in upper leaves and BYMV accumulation was inhibited in leaves developing
      post-ALSV vaccination. These results show that ALSV vaccination not only prevents
      mosaic diseases in pea, broad bean, and eustoma, but that it is also effective in
      curing these diseases.

PMID- 25386844
TI  - Twenty years of KSHV.
AB  - Twenty years ago, Kaposi's sarcoma (KS) was the oncologic counterpart to Winston
      Churchill's Russia: a riddle, wrapped in a mystery, inside an enigma. First
      described by Moritz Kaposi in 1872, who reported it to be an aggressive skin
      tumor, KS became known over the next century as a slow-growing tumor of elderly
      men-in fact, most KS patients were expected to die with the tumor rather than
      from it. Nevertheless, the course and manifestations of the disease varied widely
      in different clinical contexts. The puzzle of KS came to the forefront as a
      harbinger of the AIDS epidemic. The articles in this issue of Viruses recount
      progress made in understanding Kaposi's sarcoma herpesvirus (KSHV) since its
      initial description in 1994. 

PMID- 25386845
TI  - The Influence of Organized Physical Activity (Including Gymnastics) on Young
      Adult Skeletal Traits: Is Maturity Phase Important?
AB  - We prospectively evaluated adolescent organized physical activity (PA) as a
      factor in adult female bone traits. Annual DXA scans accompanied semiannual
      records of anthropometry, maturity, and PA for 42 participants in this
      preliminary analysis (criteria: appropriately timed DXA scans at ~1 year
      premenarche [predictor] and ~5 years postmenarche [dependent variable]).
      Regression analysis evaluated total adolescent interscan PA and PA over 3
      maturity subphases as predictors of young adult bone outcomes: 1) bone mineral
      content (BMC), geometry, and strength indices at nondominant distal radius and
      femoral neck; 2) subhead BMC; 3) lumbar spine BMC. Analyses accounted for
      baseline gynecological age (years pre- or postmenarche), baseline bone status,
      adult body size and interscan body size change. Gymnastics training was evaluated
      as a potentially independent predictor, but did not improve models for any
      outcomes (p > .07). Premenarcheal bone traits were strong predictors of most
      adult outcomes (semipartial r2 = .21-0.59, p <= .001). Adult 1/3 radius and
      subhead BMC were predicted by both total PA and PA 1-3 years postmenarche (p <
      .03). PA 3-5 years postmenarche predicted femoral narrow neck width, endosteal
      diameter, and buckling ratio (p < .05). Thus, participation in organized physical
      activity programs throughout middle and high school may reduce lifetime fracture
      risk in females. 

PMID- 25386846
TI  - Psychological, social and welfare interventions for psychological health and well
      being of torture survivors.
AB  - BACKGROUND: Torture is widespread, with potentially broad and long-lasting impact
      across physical, psychological, social and other areas of life. Its complex and
      diverse effects interact with ethnicity, gender, and refugee experience. Health
      and welfare agencies offer varied rehabilitation services, from conventional
      mental health treatment to eclectic or needs-based interventions. This review is
      needed because relatively little outcome research has been done in this field,
      and no previous systematic review has been conducted. Resources are scarce, and
      the challenges of providing services can be considerable. OBJECTIVES: To assess
      beneficial and adverse effects of psychological, social and welfare interventions
      for torture survivors, and to compare these effects with those reported by active
      and inactive controls. SEARCH METHODS: Randomised controlled trials (RCTs) were
      identified through a search of PsycINFO, MEDLINE, EMBASE, Web of Science, the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane
      Central Register of Controlled Trials (CENTRAL) and the Cochrane Depression,
      Anxiety and Neurosis Specialised Register (CCDANCTR), the Latin American and
      Caribbean Health Science Information Database (LILACS), the Open System for
      Information on Grey Literature in Europe (OpenSIGLE), the World Health
      Organization International Clinical Trials Registry Platform (WHO ICTRP) and
      Published International Literature On Traumatic Stress (PILOTS) all years to 11
      April 2013; searches of Cochrane resources, international trial registries and
      the main biomedical databases were updated on 20 June 2014. We also searched the
      Online Library of Dignity (Danish Institute against Torture), reference lists of
      reviews and included studies and the most frequently cited journals, up to April
      2013 but not repeated for 2014. Investigators were contacted to provide updates
      or details as necessary. SELECTION CRITERIA: Full publications of RCTs or quasi
      RCTs of psychological, social or welfare interventions for survivors of torture
      against any active or inactive comparison condition. DATA COLLECTION AND
      ANALYSIS: We included all major sources of grey literature in our search and used
      standard methodological procedures as expected by The Cochrane Collaboration for
      collecting data, evaluating risk of bias and using GRADE (Grades of
      Recommendation, Assessment, Development and Evaluation) methods to assess the
      quality of evidence. MAIN RESULTS: Nine RCTs were included in this review. All
      were of psychological interventions; none provided social or welfare
      interventions. The nine trials provided data for 507 adults; none involved
      children or adolescents. Eight of the nine studies described individual
      treatment, and one discussed group treatment. Six trials were conducted in
      Europe, and three in different African countries. Most people were refugees in
      their thirties and forties; most met the criteria for post-traumatic stress
      disorder (PTSD) at the outset. Four trials used narrative exposure therapy (NET),
      one cognitive-behavioural therapy (CBT) and the other four used mixed methods for
      trauma symptoms, one of which included reconciliation methods. Five interventions
      were compared with active controls, such as psychoeducation; four used treatment
      as usual or waiting list/no treatment; we analysed all control conditions
      together. Duration of therapy varied from one hour to longer than 20 hours with a
      median of around 12 to 15 hours. All trials reported effects on distress and on
      PTSD, and two reported on quality of life. Five studies followed up participants
      for at least six months.No immediate benefits of psychological therapy were noted
      in comparison with controls in terms of our primary outcome of distress (usually
      depression), nor for PTSD symptoms, PTSD caseness, or quality of life. At six
      month follow-up, three NET and one CBT study (86 participants) showed moderate
      effect sizes for intervention over control in reduction of distress (standardised
      mean difference (SMD) -0.63, 95% confidence interval (CI) -1.07 to -0.19) and of
      PTSD symptoms (SMD -0.52, 95% CI -0.97 to -0.07). However, the quality of
      evidence was very low, and risk of bias resulted from researcher/therapist
      allegiance to treatment methods, effects of uncertain asylum status of some
      people and real-time non-standardised translation of assessment measures. No
      measures of adverse events were described, nor of participation, social
      functioning, quantity of social or family relationships, proxy measures by third
      parties or satisfaction with treatment. Too few studies were identified for
      review authors to attempt sensitivity analyses. AUTHORS' CONCLUSIONS: Very low
      quality evidence suggests no differences between psychological therapies and
      controls in terms of immediate effects on post-traumatic symptoms, distress or
      quality of life; however, NET and CBT were found to confer moderate benefits in
      reducing distress and PTSD symptoms over the medium term (six months after
      treatment). Evidence was of very low quality, mainly because non-standardised
      assessment methods using interpreters were applied, and sample sizes were very
      small. Most eligible trials also revealed medium to high risk of bias. Further,
      attention to the cultural appropriateness of interventions or to their
      psychometric qualities was inadequate, and assessment measures used were
      unsuitable. As such, these findings should be interpreted with caution.No data
      were available on whether symptom reduction enabled improvements in quality of
      life, participation in community life, or in social and family relationships in
      the medium term. Details of adverse events and treatment satisfaction were not
      available immediately after treatment nor in the medium term. Future research
      should aim to address these gaps in the evidence and should include larger sample
      sizes when possible. Problems of torture survivors need to be defined far more
      broadly than by PTSD symptoms, and recognition given to the contextual influences
      of being a torture survivor, including as an asylum seeker or refugee, on
      psychological and social health.

PMID- 25386848
TI  - Mosaicism of podocyte involvement is related to podocyte injury in females with
      Fabry disease.
AB  - BACKGROUND: Fabry disease. an X-linked deficiency of alpha-galactosidase A coded
      by the GLA gene, leads to intracellular globotriaosylceramide (GL-3)
      accumulation. Although less common than in males, chronic kidney disease, occurs
      in ~ 15% of females. Recent studies highlight the importance of podocyte injury
      in Fabry nephropathy development and progression. We hypothesized that the
      greater the % of podocytes with active wild-type GLA gene (due to X-inactivation
      of the mutant copy) the less is the overall podocyte injury. METHODS: Kidney
      biopsies from 12 treatment-naive females with Fabry disease, ages 15 (8-63),
      median [range], years were studied by electron microscopy and compared with 4
      treatment-naive male patients. RESULTS: In females, 51 (13-100)% of podocytes
      (PC) per glomerulus had no GL-3 inclusions, this consistent with a non-Fabry
      podocyte phenotype (NFPC). In PC with GL-3 inclusions [Fabry podocyte phenotype
      (FPC)], GL-3 volume density per podocyte was virtually identical in females and
      males, consistent with little or no cross-correction between FPC and NFPC. %NFPC
      per glomerulus (%NFPC/glom) correlated with age in females (r = 0.65, p = 0.02),
      suggesting a survival disadvantage for FPC over time. Age-adjusted %NFPC/glom was
      inversely related to foot process width (FPW) (r = -0.75, p = 0.007), an
      indicator of PC injury. GL-3 volume density in FPC in females correlated directly
      with FPW. CONCLUSIONS: These findings support important relationships between
      podocyte mosaicism and podocyte injury in female Fabry patients. Kidney biopsy,
      by providing information about podocyte mosaicism, may help to stratify females
      with Fabry disease for kidney disease risk and to guide treatment decisions.

PMID- 25386849
TI  - Replication rates of Mycobacterium tuberculosis in human macrophages do not
      correlate with mycobacterial antibiotic susceptibility.
AB  - The standard treatment of tuberculosis (TB) takes six to nine months to complete
      and this lengthy therapy contributes to the emergence of drug-resistant TB. TB is
      caused by Mycobacterium tuberculosis (Mtb) and the ability of this bacterium to
      switch to a dormant phenotype has been suggested to be responsible for the slow
      clearance during treatment. A recent study showed that the replication rate of a
      non-virulent mycobacterium, Mycobacterium smegmatis, did not correlate with
      antibiotic susceptibility. However, the question whether this observation also
      holds true for Mtb remains unanswered. Here, in order to mimic physiological
      conditions of TB infection, we established a protocol based on long-term
      infection of primary human macrophages, featuring Mtb replicating at different
      rates inside the cells. During conditions that restricted Mtb replication, the
      bacterial phenotype was associated with reduced acid-fastness. However, these
      phenotypically altered bacteria were as sensitive to isoniazid, pyrazinamide and
      ethambutol as intracellularly replicating Mtb. In support of the recent findings
      with M. smegmatis, we conclude that replication rates of Mtb do not correlate
      with antibiotic tolerance. 

PMID- 25386850
TI  - High-throughput sequencing approach uncovers the miRNome of peritoneal
      endometriotic lesions and adjacent healthy tissues.
AB  - Accumulating data have shown the involvement of microRNAs (miRNAs) in
      endometriosis pathogenesis. In this study, we used a novel approach to determine
      the endometriotic lesion-specific miRNAs by high-throughput small RNA sequencing
      of paired samples of peritoneal endometriotic lesions and matched healthy
      surrounding tissues together with eutopic endometria of the same patients. We
      found five miRNAs specific to epithelial cells--miR-34c, miR-449a, miR-200a, miR
      200b and miR-141 showing significantly higher expression in peritoneal
      endometriotic lesions compared to healthy peritoneal tissues. We also determined
      the expression levels of miR-200 family target genes E-cadherin, ZEB1 and ZEB2
      and found that the expression level of E-cadherin was significantly higher in
      endometriotic lesions compared to healthy tissues. Further evaluation verified
      that studied miRNAs could be used as diagnostic markers for confirming the
      presence of endometrial cells in endometriotic lesion biopsy samples.
      Furthermore, we demonstrated that the miRNA profile of peritoneal endometriotic
      lesion biopsies is largely masked by the surrounding peritoneal tissue,
      challenging the discovery of an accurate lesion-specific miRNA profile. Taken
      together, our findings indicate that only particular miRNAs with a significantly
      higher expression in endometriotic cells can be detected from lesion biopsies,
      and can serve as diagnostic markers for endometriosis.

PMID- 25386851
TI  - Evidence of uncoupling between renal dysfunction and injury in cardiorenal
      syndrome: insights from the BIONICS study.
AB  - OBJECTIVE: The objective of the study was to assess urinary biomarkers of renal
      injury for their individual or collective ability to predict Worsening renal
      function (WRF) in patients with acutely decompensated heart failure (ADHF).
      METHODS: In a prospective, blinded international study, 87 emergency department
      (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type
      natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2),
      biomarkers of renal function (creatinine, estimated glomerular filtration rate
      [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated
      lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D
      glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint
      was WRF. RESULTS: 26% developed WRF; baseline characteristics of subjects who
      developed WRF were generally comparable to those who did not. Biomarkers of renal
      function and urine biomarkers of renal injury were not correlated, while urine
      biomarkers of renal injury correlated between each other. Biomarker
      concentrations were similar between patients with and without WRF except for
      baseline BNP. Although plasma NGAL was associated with the combined endpoint,
      none of the biomarker showed predictive accuracy for WRF. CONCLUSIONS: In ED
      patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our
      data suggest that a weak association exists between renal dysfunction and renal
      injury in this setting (Clinicaltrials.gov NCT#0150153).

PMID- 25386852
TI  - A Drosophila toolkit for the visualization and quantification of viral
      replication launched from transgenic genomes.
AB  - Arthropod RNA viruses pose a serious threat to human health, yet many aspects of
      their replication cycle remain incompletely understood. Here we describe a
      versatile Drosophila toolkit of transgenic, self-replicating genomes
      ('replicons') from Sindbis virus that allow rapid visualization and
      quantification of viral replication in vivo. We generated replicons expressing
      Luciferase for the quantification of viral replication, serving as useful new
      tools for large-scale genetic screens for identifying cellular pathways that
      influence viral replication. We also present a new binary system in which
      replication-deficient viral genomes can be activated 'in trans', through co
      expression of an intact replicon contributing an RNA-dependent RNA polymerase.
      The utility of this toolkit for studying virus biology is demonstrated by the
      observation of stochastic exclusion between replicons expressing different
      fluorescent proteins, when co-expressed under control of the same cellular
      promoter. This process is analogous to 'superinfection exclusion' between virus
      particles in cell culture, a process that is incompletely understood. We show
      that viral polymerases strongly prefer to replicate the genome that encoded them,
      and that almost invariably only a single virus genome is stochastically chosen
      for replication in each cell. Our in vivo system now makes this process amenable
      to detailed genetic dissection. Thus, this toolkit allows the cell-type specific,
      quantitative study of viral replication in a genetic model organism, opening new
      avenues for molecular, genetic and pharmacological dissection of virus biology
      and tool development. 

PMID- 25386853
TI  - Tiny is mighty: seagrass beds have a large role in the export of organic material
      in the tropical coastal zone.
AB  - Ecosystems in the tropical coastal zone exchange particulate organic matter (POM)
      with adjacent systems, but differences in this function among ecosystems remain
      poorly quantified. Seagrass beds are often a relatively small section of this
      coastal zone, but have a potentially much larger ecological influence than
      suggested by their surface area. Using stable isotopes as tracers of oceanic,
      terrestrial, mangrove and seagrass sources, we investigated the origin of
      particulate organic matter in nine mangrove bays around the island of Phuket
      (Thailand). We used a linear mixing model based on bulk organic carbon, total
      nitrogen and delta13C and delta15N and found that oceanic sources dominated
      suspended particulate organic matter samples along the mangrove-seagrass-ocean
      gradient. Sediment trap samples showed contributions from four sources oceanic,
      mangrove forest/terrestrial and seagrass beds where oceanic had the strongest
      contribution and seagrass beds the smallest. Based on ecosystem area, however,
      the contribution of suspended particulate organic matter derived from seagrass
      beds was disproportionally high, relative to the entire area occupied by mangrove
      forests, the catchment area (terrestrial) and seagrass beds. The contribution
      from mangrove forests was approximately equal to their surface area, whereas
      terrestrial contributions to suspended organic matter under contributed compared
      to their relative catchment area. Interestingly, mangrove forest contribution at
      0 m on the transects showed a positive relationship with the exposed frontal
      width of the mangrove, indicating that mangrove forest exposure to hydrodynamic
      energy may be a controlling factor in mangrove outwelling. However we found no
      relationship between seagrass bed contribution and any physical factors, which we
      measured. Our results indicate that although seagrass beds occupy a relatively
      small area of the coastal zone, their role in the export of organic matter is
      disproportional and should be considered in coastal management especially with
      respect to their importance as a nutrient source for other ecosystems and
      organisms. 

PMID- 25386854
TI  - Serum uric acid and nigral iron deposition in Parkinson's disease: a pilot study.
AB  - BACKGROUND: Uric acid (UA) is an endogenous antioxidant which is known to reduce
      oxidative stress and also chelate iron ion. Recent studies have provided evidence
      that UA may play a neuroprotective role in Parkinson's disease (PD). However, it
      is unknown whether UA relates to nigral iron deposition, which is a
      characteristic pathophysiological alteration in PD. The aim of this study was to
      determine the potential relationship of these two markers in patients with PD.
      METHODS: A total of 30 patients of PD and 25 age- and gender- matched healthy
      controls underwent 3-Tesla MRI and laboratory tests including serum UA levels. We
      assessed iron levels by measuring phase shift values using susceptibility
      weighted image. Mean phase shift values of the substantia nigra (SN), red
      nucleus, head of the caudate nucleus, globus pallidus, putamen, thalamus, and
      frontal white matter were calculated and correlated with serum UA levels.
      RESULTS: Serum UA levels were significantly decreased in the PD patients than in
      the controls. Phase shift values in bilateral SN were significantly increased in
      the PD patients than in the controls. There was no significant correlation
      between serum UA levels and nigral phase shift values. CONCLUSIONS: As previous
      studies, low serum UA level and increased nigral iron content in the PD was
      reconfirmed in this study. However, we failed to find the relationship between
      these two markers. Our data suggest that serum UA may not be important
      determinant of nigral iron deposition in PD.

PMID- 25386855
TI  - A hybrid search algorithm for swarm robots searching in an unknown environment.
AB  - This paper proposes a novel method to improve the efficiency of a swarm of robots
      searching in an unknown environment. The approach focuses on the process of
      feeding and individual coordination characteristics inspired by the foraging
      behavior in nature. A predatory strategy was used for searching; hence, this
      hybrid approach integrated a random search technique with a dynamic particle
      swarm optimization (DPSO) search algorithm. If a search robot could not find any
      target information, it used a random search algorithm for a global search. If the
      robot found any target information in a region, the DPSO search algorithm was
      used for a local search. This particle swarm optimization search algorithm is
      dynamic as all the parameters in the algorithm are refreshed synchronously
      through a communication mechanism until the robots find the target position,
      after which, the robots fall back to a random searching mode. Thus, in this
      searching strategy, the robots alternated between two searching algorithms until
      the whole area was covered. During the searching process, the robots used a local
      communication mechanism to share map information and DPSO parameters to reduce
      the communication burden and overcome hardware limitations. If the search area is
      very large, search efficiency may be greatly reduced if only one robot searches
      an entire region given the limited resources available and time constraints. In
      this research we divided the entire search area into several subregions, selected
      a target utility function to determine which subregion should be initially
      searched and thereby reduced the residence time of the target to improve search
      efficiency. 

PMID- 25386856
TI  - Nogo receptor 1 limits tactile task performance independent of basal anatomical
      plasticity.
AB  - The genes that govern how experience refines neural circuitry and alters synaptic
      structural plasticity are poorly understood. The nogo-66 receptor 1 gene (ngr1)
      is one candidate that may restrict the rate of learning as well as basal
      anatomical plasticity in adult cerebral cortex. To investigate if ngr1 limits the
      rate of learning we tested adult ngr1 null mice on a tactile learning task. Ngr1
      mutants display greater overall performance despite a normal rate of improvement
      on the gap-cross assay, a whisker-dependent learning paradigm. To determine if
      ngr1 restricts basal anatomical plasticity in the associated sensory cortex, we
      repeatedly imaged dendritic spines and axonal varicosities of both constitutive
      and conditional adult ngr1 mutant mice in somatosensory barrel cortex for two
      weeks through cranial windows with two-photon chronic in vivo imaging. Neither
      constant nor acute deletion of ngr1 affected turnover or stability of dendritic
      spines or axonal boutons. The improved performance on the gap-cross task is not
      attributable to greater motor coordination, as ngr1 mutant mice possess a mild
      deficit in overall performance and a normal learning rate on the rotarod, a motor
      task. Mice lacking ngr1 also exhibit normal induction of tone-associated fear
      conditioning yet accelerated fear extinction and impaired consolidation. Thus,
      ngr1 alters tactile and motor task performance but does not appear to limit the
      rate of tactile or motor learning, nor determine the low set point for synaptic
      turnover in sensory cortex. 

PMID- 25386858
TI  - Benefit of negative pressure drain within surgical wound after cytoreductive
      surgery for ovarian cancer.
AB  - OBJECTIVE: The objective of this study was to investigate the efficacy of
      subcutaneous negative-pressure wound drains on wound healing after cytoreductive
      surgery for ovarian cancer. METHODS: A retrospective study was performed on
      patients who underwent cytoreductive surgery for epithelial ovarian cancer,
      between 2012 and 2013. The patients were divided into 2 groups, according to
      using (n = 163) and not using (n = 37) of subcutaneous wound drains, and wound
      outcomes were analyzed. RESULTS: Patients' characteristics were not statistically
      different, except for the prolonged operative time in patients with wound drains
      (median, 395 vs 240 minutes; P = 0.001). A lower rate of wound infection (12.9%
      vs 27.0%; P = 0.032) was observed in the drain group. In the multivariate
      analysis, placement of subcutaneous wound drain was an independent prognostic
      factor for reducing wound complications: disruption (odds ratio [OR], 0.367; 95%
      confidence interval [CI], 0.145-0.929; P = 0.034) and wound infection (OR, 0.198;
      95% CI, 0.068-0.582; P = 0.003). Bowel surgery at the time of cytoreductive
      surgery and prolonged operative time (>=360 minutes) were also associated with
      higher rates of disruption (OR, 2.845; 95% CI, 1.111-7.289; P = 0.029) and wound
      infection (OR, 4.212; 95% CI, 1.273-13.935; P = 0.019), respectively.
      CONCLUSIONS: Installation of subcutaneous negative-pressure wound drain is an
      effective method to achieve clearer wound healing and less wound complications
      after cytoreductive surgery for ovarian cancer.

PMID- 25386857
TI  - Oral manifestations in the American tegumentary leishmaniasis.
AB  - INTRODUCTION: American tegumentary leishmaniasis (ATL) can affect the skin or
      mucosa (mucocutaneous leishmaniasis - MCL) including the oral cavity. MCL oral
      lesions are often confused with other oral diseases, delaying diagnosis and
      specific treatment, and increasing the likelihood of sequelae. Thus, increasing
      the knowledge of the evolution of ATL oral lesions can facilitate its early
      diagnosis improving the prognosis of healing. OBJECTIVES: Evaluate the frequency
      of ATL oral lesion and describe its clinical, laboratory and therapeutic
      peculiarities. METHODS: A descriptive transversal study was carried out, using
      data from medical records of 206 patients with MCL examined at the outpatient
      clinics-IPEC-Fiocruz between 1989 and 2013. Proportions were calculated for the
      categorical variables and the association among them was assessed by the
      Pearson's chi-square test. Measures of central tendency and dispersion were used
      for the continuous variables and their differences were assessed by both
      parametric (t test) and non parametric (Mann-Whitney) tests. P-values <0.05 were
      considered as significant. RESULTS: The most affected site was the nose, followed
      by the mouth, pharynx and larynx. Seventy eight (37.9%) have oral lesions and the
      disease presented a lower median of the evolution time than in other mucous sites
      as well as an increased time to heal. The presence of oral lesion was associated
      with: the presence of lesions in the other three mucosal sites; a smaller median
      of the leishmanin skin test values; a longer healing time of the mucosal lesions;
      a higher recurrence frequency; and a smaller frequency of treatment finishing and
      healing. When the oral lesion was isolated, it was associated with an age 20
      years lower than when the oral lesion was associated with other mucosal sites.
      CONCLUSION: Considering the worst therapy results associated with the presence of
      oral lesions, we suggest that lesions in this location represent a factor of
      worse prognosis for MCL.

PMID- 25386859
TI  - Comparison of lymphedema incidence between 2 lymphadenectomy techniques in
      patients with uterine cancer undergoing robotic staging.
AB  - OBJECTIVE: This study aimed to compare the incidence of lower extremity
      lymphedema in patients with uterine cancer after robotic staging using the
      following 2 methods: standard and selective pelvic lymphadenectomy. MATERIALS AND
      METHODS: Three hundred forty-four consecutive patients who presented with
      endometrial cancer from March 2007 to October 2012 underwent robotic staging.
      Surgeon A performed standard pelvic lymphadenectomy and surgeon B performed
      selective lymphadenectomy. Selective pelvic lymphadenectomy spared the lateral
      chain of the external iliac lymph nodes (LNs). The incidence of lymphedema and
      staging adequacy between the 2 groups were analyzed. RESULTS: Standard pelvic
      lymphadenectomy was performed in 238/344 (69.2%) patients and selective pelvic
      lymphadenectomy was performed in 106/344 (30.8%) patients. Conversion to
      laparotomy occurred in 2/344 cases (0.6%). Mean age for 344 patients was 63.6
      (10) years and body mass index was 34.8 (10.1) kg/m(2). The mean operative time
      was 162.3 (54.6) minutes. Postoperative hospitalization was 1.62 (1.93) days.
      Histology included 80.8% endometrioid adenocarcinomas and 19.2% clear cell,
      serous, and carcinosarcomas. Mean pelvic LN counts for the standard and selective
      pelvic lymphadenectomy groups were 16 (8.6) and 15.5 (7.1), respectively (P =
      0.31). Mean numbers of para-aortic LNs retrieved for the standard and selective
      lymphadenectomy groups were 3.1 (4.1) and 4.9 (4.5), respectively (P <
      0.01).Median follow-up was 29.3 months (interquartile range, 15.6-43.1 months).
      The difference in the incidence of lower extremity lymphedema was statistically
      significant: 4.6% (11/238 patients) in the standard lymphadenectomy group versus
      0.9% (1/106 patients) in the selective lymphadenectomy group (P = 0.03).
      CONCLUSIONS: When compared to the standard technique, selective pelvic
      lymphadenectomy with sparing of the lateral chain of the external iliac LNs is
      adequate and results in a lower incidence of lower extremity lymphedema.

PMID- 25386860
TI  - Comment on 'Residential distance at birth from overhead high-voltage powerlines:
      childhood cancer risk in Britain 1962-2008'.

PMID- 25386861
TI  - A new policy to implement CONSORT guidelines for surgical randomized controlled
      trials.

PMID- 25386863
TI  - The danger of complacency - readiness and preparedness = effective outcomes.

PMID- 25386862
TI  - The initial response to the Boston marathon bombing: lessons learned to prepare
      for the next disaster.
AB  - OBJECTIVE: We discuss the strengths of the medical response to the Boston
      Marathon bombings that led to the excellent outcomes. Potential shortcomings were
      recognized, and lessons learned will provide a foundation for further
      improvements applicable to all institutions. BACKGROUND: Multiple casualty
      incidents from natural or man-made incidents remain a constant global threat.
      Adequate preparation and the appropriate alignment of resources with immediate
      needs remain the key to optimal outcomes. METHODS: A collaborative effort among
      Boston's trauma centers (2 level I adult, 3 combined level I adult/pediatric, 1
      freestanding level I pediatric) examined the details and outcomes of the initial
      response. Each center entered its respective data into a central database
      (REDCap), and the data were analyzed to determine various prehospital and early
      in-hospital clinical and logistical parameters that collectively define the
      citywide medical response to the terrorist attack. RESULTS: A total of 281 people
      were injured, and 127 patients received care at the participating trauma centers
      on that day. There were 3 (1%) immediate fatalities at the scene and no in
      hospital mortality. A majority of the patients admitted (66.6%) suffered lower
      extremity soft tissue and bony injuries, and 31 had evidence for exsanguinating
      hemorrhage, with field tourniquets in place in 26 patients. Of the 75 patients
      admitted, 54 underwent urgent surgical intervention and 12 (22%) underwent
      amputation of a lower extremity. CONCLUSIONS: Adequate preparation, rapid
      logistical response, short transport times, immediate access to operating rooms,
      methodical multidisciplinary care delivery, and good fortune contributed to
      excellent outcomes.

PMID- 25386864
TI  - Statement on surgical preresidency preparatory courses.
AB  - The leadership of the surgical community is actively engaged in improving the
      preparation of incoming residents to assume responsibility and accountability for
      key elements of care and stewardship. To better prepare for this transition, it
      is essential that all matriculants to surgery residency successfully complete a
      preparatory course of blended learning that specifically addresses essential
      components of quality care and patient safety before the start of their training.
      A national multidimensional curriculum, along with objective assessment tools,
      has been developed to accelerate readiness, responsibility, and accountability
      during the transition from medical school to surgery residency. We strongly
      endorse this effort and encourage medical schools to adopt this or a similar
      program. We stand ready to assist medical schools and medical students in
      implementation of this important initiative. 

PMID- 25386865
TI  - Effectiveness of propolis on oral health: a meta-analysis.
AB  - BACKGROUND: The use of propolis mouth rinse or gel as a supplementary
      intervention has increased during the last decade in Taiwan. However, the effect
      of propolis on oral health is not well understood. PURPOSE: The purpose of this
      meta-analysis was to present the best available evidence regarding the effects of
      propolis use on oral health, including oral infection, dental plaque, and
      stomatitis. METHODS: Researchers searched seven electronic databases for relevant
      articles published between 1969 and 2012. Data were collected using inclusion and
      exclusion criteria. The Joanna Briggs Institute Meta Analysis of Statistics
      Assessment and Review Instrument was used to evaluate the quality of the
      identified articles. RESULTS: Eight trials published from 1997 to 2011 with 194
      participants had extractable data. The result of the meta-analysis indicated
      that, although propolis had an effect on reducing dental plaque, this effect was
      not statistically significant. The results were not statistically significant for
      oral infection or stomatitis. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Although
      there are a number of promising indications, in view of the limited number and
      quality of studies and the variation in results among studies, this review
      highlights the need for additional well-designed trials to draw conclusions that
      are more robust.

PMID- 25386866
TI  - Diabetes self-care behaviors and disease control in support group attenders and
      nonattenders.
AB  - BACKGROUND: The prevalence rate and mortality rate of diabetes continue to
      increase annually. Complications associated with poor control of diabetes include
      renal dialysis, amputation, heart disease, stroke, retinopathy, and vascular
      disease, all of which have an impact at the individual, family, and national
      level. PURPOSE: This study compares diabetes self-care behavior and disease
      control efficacy between attenders and nonattenders of a diabetes support group.
      METHODS: We used a questionnaire with good validity and reliability to conduct a
      cross-sectional survey. Diabetes support groups have been established throughout
      Taiwan for around 2 years. Participants for this study were recruited randomly
      from a register of support group participants. Support group instructors were
      asked to collect questionnaires from those attending and not attending their
      support groups. Ten groups volunteered to participate in this study. We received
      147 valid questionnaires from participants attending support groups (attenders)
      and 93 questionnaires from participants who did not (nonattenders). RESULTS:
      There were no statistically significant differences between support group
      attenders and nonattenders in terms of age, educational level, or time since
      diagnosis of diabetes. Thus, we assumed these two groups as adequately similar to
      conduct statistical comparisons. Scores for diabetes self-care behavior, disease
      control, and use of the diabetes passport were all significantly higher among
      support group attenders than their nonattender peers. CONCLUSIONS/IMPLICATIONS
      FOR PRACTICE: Results indicate that people attending diabetes support groups are
      more likely to have better self-care behavior and disease control than
      nonattenders. Therefore, we suggest that the government actively promote policies
      supportive of diabetes support groups.

PMID- 25386867
TI  - The exercise patterns of pregnant women in Taiwan.
AB  - BACKGROUND: Unless advised otherwise by their doctor, pregnant women should get
      approximately 30 minutes of moderate exercise on most days. However, most
      pregnant women do not exercise regularly and do not meet the American College of
      Obstetricians Gynecology's standard for the minimum amount of exercise needed to
      stay healthy during pregnancy. PURPOSE: We investigate the factors related to
      regular exercise among pregnant women and describe the type, duration, and change
      in regular exercise from prepregnancy to pregnancy in Taiwan. METHODS: Pregnant
      women (N = 692) completed a questionnaire on exercise habits and were then
      grouped into regular exercise (105, 15.2%) and nonregular exercise (587, 84.8%)
      groups. Demographic and exercise-related variables were then investigated for
      their association with exercise during pregnancy. RESULTS: Work status,
      prepregnancy exercise, and trimester were significant predictors of regular
      exercise during pregnancy. The most commonly reported exercise types were
      walking, climbing stairs, and yoga. Nearly four fifths (n = 526, 76.0%) of
      participants did not exercise regularly before pregnancy, whereas 42.9% of
      participants continued exercising regularly after becoming pregnant. Among those
      who were inactive before pregnancy, 10.1% began exercising after becoming
      pregnant. In contrast, 57.1% of participants who had been more active before
      pregnancy stopped exercising regularly after becoming pregnant. Overall, it was
      found that participants decreased their amount (minutes * times/week) of exercise
      compared with their prepregnancy amount. CONCLUSIONS: Results suggest that
      walking and climbing stairs, each beneficial to the health of pregnant women, are
      the most common types of regular exercise engaged in by pregnant women in Taiwan.
      Regular exercise benefits the health of pregnant women. The findings of this
      study may be useful to doctors and nurses responsible to counsel pregnant women
      to exercise regularly and to have a reasonably active lifestyle during pregnancy.

PMID- 25386868
TI  - Predictors of hyperphagia in institutionalized patients with dementia.
AB  - BACKGROUND: Hyperphagia, a common eating behavioral change in patients with
      dementia, is one of the risk factors for institutional placement. No study of
      hyperphagia has yet been conducted on institutionalized patients with dementia.
      There is currently no academic consensus over the correlations among hyperphagic
      behaviors, agitated behaviors, cognitive function, and demographic
      characteristics in this patient group. PURPOSE: This study explores the
      prevalence and predictors of hyperphagic behaviors in institutionalized patients
      with dementia. METHODS: A cross-sectional and correlational design was used. The
      participants were recruited from seven dementia special care units and assisted
      living facilities in Taiwan. One hundred seventy-nine patients with dementia
      agreed to participate. Two research assistants were trained to collect data using
      the subscale for hyperphagic behaviors, the Cohen-Mansfield Agitation Inventory,
      the Cognitive Abilities Screening Instrument, and a dementia patient demographic
      characteristics datasheet. RESULTS: The prevalence of hyperphagic behaviors in
      institutionalized patients with dementia was 50.8% (91/179). After excluding the
      variables from the long-term memory, short-term memory, attention, abstraction
      and judgment, and verbally nonaggressive behavior subscales scores, we found
      gender, length of institutionalization, category fluency, and physically
      nonaggressive behavior subscale scores to be significant predictors of
      hyperphagic behaviors (p < .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Findings
      suggest that institutionalized male patients with dementia with longer
      institutionalization who have either a relatively low-fluency task score or a
      relatively high frequency of physically nonaggressive behaviors are at greater
      risk for exhibiting hyperphagic behaviors. Once hyperphagic behaviors are found
      in a patient, a transdisciplinary case meeting should be held to develop an
      appropriate dietary management plan, and further identification and treatment
      should be done by a neurologist or a psychiatrist.

PMID- 25386869
TI  - Psychometric properties of the Persian version of the Critical Care Family Needs
      Inventory.
AB  - BACKGROUND: Life-threatening illnesses and subsequent hospitalization in the
      intensive care unit (ICU) often occur unexpectedly. In many cases, this event is
      devastating for families and may lead to emotional stress, anxiety, and fear. To
      offer comprehensive and high-quality nursing care, critical care nurses not only
      provide critical care to patients but also attend to the psychological and social
      needs of patients and their families. PURPOSE: The purpose of this study was to
      assess the psychometric properties of the Persian version of the Critical Care
      Family Needs Inventory (CCFNI-P). METHODS: This was a cross-sectional
      methodological research study. Forward-backward translation was used to develop
      the instrument. The first version was pretested with 10 families to assess face
      validity. The main sample consisted of 720 family members of hospitalized
      patients, composed of 360 admitted to ICUs and 360 admitted to general wards of
      hospitals in Tehran, Iran. Participants were selected randomly to evaluate the
      instrument in terms of known-groups, construct, and convergent validities. The
      internal consistency of the translated instrument was assessed using Cronbach's
      alpha coefficient. RESULTS: A significant difference was found between the scores
      of participants with patients in ICUs and participants with patients in the
      general wards (p < .001). In agreement with the original instrument, five
      distinct components were extracted from the CCFNI-P, which accounted for more
      than 52% of the total variance. The correlation between the total score for the
      instrument and the State-Trait Anxiety Inventory criterion was positive and
      significant (r = .23, p < .04). The Cronbach's alpha coefficient for the entire
      instrument was .89 and more than .70 for all dimensions. CONCLUSIONS: This study
      confirmed the validity of the CCFNI-P in terms of face, construct, convergent,
      and known groups and showed acceptable internal consistency. The CCFNI-P is valid
      for investigating the needs of Iranians who have a family member hospitalized in
      an ICU.

PMID- 25386870
TI  - Iranian families' experience of receiving support during their patients' surgical
      process: qualitative study.
AB  - BACKGROUND: The time spent waiting through the surgery of a loved one is
      stressful for family members because of their worries regarding the procedure and
      potential outcomes. In Iran, the attention and support of healthcare
      professionals focus almost exclusively on the patient. No studies have explored
      the related support experiences of family members. Understanding these
      experiences may facilitate the development by healthcare professionals of support
      strategies to alleviate the surgery-related stresses of patients' family members.
      PURPOSE: This study elucidates the support experiences of the Iranian families of
      patients undergoing surgery. METHODS: A qualitative design using a content
      analysis approach was used to gather and analyze the support experiences of 16
      Iranian families awaiting the conclusion of their relative's surgical operation.
      The study was conducted at a university medical center hospital in an urban area
      in Iran. After employing a purposive sampling method to select participants,
      semistructured interviews were used to collect data. RESULTS: Data analysis led
      to the development of two main themes: "interaction:" and "physical proximity."
      One significant finding was the role of productive interactions among family
      members to facilitate the passing of time and to provide a buffer. These
      interactions may take place among family members as well as among other
      companions. CONCLUSIONS: The findings of this study may be used to guide nursing
      practices and may help change nursing attitudes toward the family members of
      surgical patients. By better understanding the experience of families, nurses may
      improve their professional actions and reduce the stress experienced by family
      members while waiting for the conclusion of surgery.

PMID- 25386871
TI  - Confronting the diagnosis of multiple sclerosis: a qualitative study of patient
      experiences.
AB  - BACKGROUND: Multiple sclerosis (MS) involves complex physical and mental
      disabilities and often results in family, occupational, and social problems that
      cause difficulties in confronting the diagnosis of MS, which may delay or deny
      acceptance of the disease. Therefore, it is important to understand the
      experiences of patients in facing this disease to help and support families,
      communities, and healthcare teams more effectively. PURPOSE: This study explores
      the experiences of patients in confronting their diagnosis of MS. METHODS: A
      qualitative content analysis method was used in this study. The study
      participants were 25 people with MS chosen via purposeful sampling from the MS
      associations in Isfahan and Tehran (Iran). Data were collected using unstructured
      interviews and analyzed using content analysis. RESULTS: The analysis resulted in
      the emergence of four themes and 11 subthemes. The main themes were knowledge
      deficit, concealing the disease, religiosity, and emotional reactions.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings highlight the principal means
      by which patients confront a diagnosis of MS and the needs and challenges
      involved in transiting successfully to acceptance and treatment. The authors hope
      the findings of this study will increase the information available to families
      and nurses regarding the reaction of patients to an MS diagnosis and have a
      positive impact on support programs designed to help patients confront and adapt
      to MS. Furthermore, these findings may serve to create a framework for developing
      related nursing care processes and establishing counseling and support programs
      that are sensitive to the religious, ideological, and cultural backgrounds of
      patients.

PMID- 25386872
TI  - Long-term evaluation of Class II subdivision treatment with unilateral maxillary
      first molar extraction.
AB  - OBJECTIVE: To evaluate the long-term effects of asymmetrical maxillary first
      molar (M1) extraction in Class II subdivision treatment. MATERIALS AND METHODS:
      Records of 20 Class II subdivision whites (7 boys, 13 girls; mean age, 13.0
      years; SD, 1.7 years) consecutively treated with the Begg technique and M1
      extraction, and 15 untreated asymmetrical Class II adolescents (4 boys, 11 girls;
      mean age, 12.2 years; SD, 1.3 years) were examined in this study. Cephalometric
      analysis and PAR assessment were carried out before treatment (T1), after
      treatment (T2), and on average 2.5 years posttreatment (T3) for the treatment
      group, and at similar time points and average follow-up of 1.8 years for the
      controls. RESULTS: The adjusted analysis indicated that the maxillary incisors
      were 2.3 mm more retracted in relation to A-Pog between T1 and T3 (beta  =  2.31;
      95% CI; 0.76, 3.87), whereas the mandibular incisors were 1.3 mm more protracted
      (beta  =  1.34; 95% CI; 0.09, 2.59), and 5.9 degrees  more proclined to the
      mandibular plane (beta  =  5.92; 95% CI; 1.43, 10.41) compared with controls. The
      lower lip appeared 1.4 mm more protrusive relative to the subnasale-soft tissue
      Pog line throughout the observation period in the treated adolescents (beta  = 
      1.43; 95% CI; 0.18, 2.67). There was a significant PAR score reduction over the
      entire follow-up period in the molar extraction group (beta  =  -6.73; 95% CI; 
      10.7, -2.7). At T2, 65% of the subjects had maxillary midlines perfectly aligned
      with the face. CONCLUSIONS: Unilateral M1 extraction in asymmetrical Class II
      cases may lead to favorable occlusal outcomes in the long term without harming
      the midline esthetics and soft tissue profile.

PMID- 25386873
TI  - Perfluoroalkyl acid uptake in lettuce (Lactuca sativa) and strawberry (Fragaria
      ananassa) irrigated with reclaimed water.
AB  - Using reclaimed water to irrigate food crops presents an exposure pathway for
      persistent organic contaminants such as perfluoroalkyl acids (PFAAs) to enter the
      human food chain. This greenhouse study used reclaimed water augmented with
      varying concentrations (0.2-40 MUg/L) of PFAAs, including perfluorocarboxylates
      (C3F7COO(-) to C8F17COO(-)) and perfluorosulfonates (C4F9SO2O(-), C6F13SO2O(-),
      C8F17SO2O(-)), to investigate potential uptake and concentration-response trends
      in lettuce (Lactuca sativa) and strawberry (Fragaria ananassa). In addition,
      studies were conducted to evaluate the role of soil organic carbon concentrations
      on plant uptake of PFAAs. PFAA concentrations in lettuce leaves and strawberry
      fruit were measured for each aqueous PFAA concentration applied. PFAA plant
      concentrations increased linearly with the aqueous concentration for all PFAAs,
      with PFCAs bioaccumulating to a greater degree than PFSAs in the edible portions
      of the tested plants. Chain-length-dependency trends were evident in both lettuce
      shoot and strawberry fruit, with decreasing concentrations associated with
      increasing chain length. Perfluorobutanoate (PFBA) and perfluoropentanoate
      (PFPeA), both short-chain PFAAs (<8 carbon chain length), accumulated the most
      compared with other PFAAs tested in the edible parts of both lettuce and
      strawberry. PFAA concentrations in strawberry root and shoot were also measured
      at selected PFAA aqueous concentrations (0.4, 4, and 40 MUg/L). Short-chain
      perfluorocarboxylates were the dominant fraction in the strawberry fruit and
      shoot compartments, whereas a more even distribution of all PFAAs appeared in the
      root compartment. Lettuce grown in soils with varying organic carbon contents
      (0.4%, 2%, 6%) was used to assess the impact of organic carbon sorption on PFAA
      bioaccumulation. The lettuce grown in soil with the 6% organic carbon content had
      the lowest bioaccumulation of PFAAs. Bioaccumulation factors for lettuce were
      correlated to carbon chain length of PFAAs, showing approximately a 0.4 to 0.6
      log decrease per CF2 group. This study confirms that PFAAs can enter and
      bioaccumulate in food crops irrigated with reclaimed water. Bioaccumulation
      potential depends on analyte functional group and chain length, concentration in
      the reclaimed water, and organic carbon content of the soil. 

PMID- 25386875
TI  - Digital breast tomosynthesis-guided vacuum-assisted breast biopsy: initial
      experiences and comparison with prone stereotactic vacuum-assisted biopsy.
AB  - PURPOSE: To use digital breast tomosynthesis (DBT)-guided vacuum-assisted biopsy
      (VAB) to sample target lesions identified at full-field digital screening
      mammography and compare clinical performance with that of prone stereotactic (PS)
      VAB. MATERIALS AND METHODS: In this institutional review board-approved study,
      205 patients with 216 mammographic findings suspicious for cancer were scheduled
      to undergo mammography-guided VAB. Written informed consent was obtained. PS VAB
      was performed in 159 patients with 165 target lesions. DBT VAB was performed in
      46 consecutive patients with 51 target lesions. Tissue-sampling methods and
      materials (9-gauge needles) were the same with both systems. For calcifications,
      specimen radiographs were obtained, and for masses or architectural distortions,
      control mammography or DBT was performed to confirm adequate target lesion
      sampling. chi(2) and Student t tests were used to compare biopsy time, and the
      Fisher exact test was used to compare lesion type distribution for DBT versus PS
      VAB. RESULTS: Technical success was achieved in 51 of 51 lesions (100%) with DBT
      VAB versus 154 of 165 lesions (93%) with PS VAB. In one of 11 lesions in which PS
      VAB failed, DBT VAB was performed successfully. Mean time to complete VAB was 13
      minutes +/- 3.7 for DBT VAB versus 29 minutes +/- 10.1 for PS VAB (P < .0001).
      Reidentifying and targeting lesions during PS VAB took longer than it did during
      DBT VAB (P < .0001). Tissue sampling took about the same time for PS VAB and DBT
      VAB (P = .067). Significantly more "low-contrast" (ie, uncalcified) target
      lesions were biopsied with DBT VAB (13 of 51 lesions) versus PS VAB (nine of 165
      lesions) (P < .0002). No major complications were observed with either system.
      One patient who underwent DBT VAB in the sitting position and one patient who
      underwent PS VAB developed self-limiting vasovagal reactions. CONCLUSION:
      Clinical performance of DBT VAB was significantly superior to PS VAB. Because DBT
      VAB allows use of the full detector size for imaging and provides immediate
      lesion depth information without requiring triangulation, it facilitates target
      lesion reidentification and sampling of even low-contrast targets, such as
      uncalcified masses.

PMID- 25386874
TI  - Variation of densitometry on computed tomography in COPD--influence of different
      software tools.
AB  - OBJECTIVES: Quantitative multidetector computed tomography (MDCT) as a potential
      biomarker is increasingly used for severity assessment of emphysema in chronic
      obstructive pulmonary disease (COPD). Aim of this study was to evaluate the user
      independent measurement variability between five different fully-automatic
      densitometry software tools. MATERIAL AND METHODS: MDCT and full-body
      plethysmography incl. forced expiratory volume in 1s and total lung capacity were
      available for 49 patients with advanced COPD (age = 64+/-9 years, forced
      expiratory volume in 1 s = 31+/-6% predicted). Measurement variation regarding
      lung volume, emphysema volume, emphysema index, and mean lung density was
      evaluated for two scientific and three commercially available lung densitometry
      software tools designed to analyze MDCT from different scanner types. RESULTS:
      One scientific tool and one commercial tool failed to process most or all
      datasets, respectively, and were excluded. One scientific and another commercial
      tool analyzed 49, the remaining commercial tool 30 datasets. Lung volume,
      emphysema volume, emphysema index and mean lung density were significantly
      different amongst these three tools (p<0.001). Limits of agreement for lung
      volume were [-0.195, -0.052 l], [-0.305, -0.131 l], and [-0.123, -0.052 l] with
      correlation coefficients of r = 1.00 each. Limits of agreement for emphysema
      index were [-6.2, 2.9%], [-27.0, 16.9%], and [-25.5, 18.8%], with r = 0.79 to
      0.98. Correlation of lung volume with total lung capacity was good to excellent
      (r = 0.77 to 0.91, p<0.001), but segmented lung volume (6.7+/-1.3-6.8+/-1.3 l)
      were significantly lower than total lung capacity (7.7+/-1.7 l, p<0.001).
      CONCLUSIONS: Technical incompatibilities hindered evaluation of two of five
      tools. The remaining three showed significant measurement variation for
      emphysema, hampering quantitative MDCT as a biomarker in COPD. Follow-up studies
      should currently use identical software, and standardization efforts should
      encompass software as well.

PMID- 25386876
TI  - Direct evaluation of radiobiological parameters from clinical data in the case of
      ion beam therapy: an alternative approach to the relative biological
      effectiveness.
AB  - The relative biological effectiveness (RBE) concept is commonly used in treatment
      planning for ion beam therapy. Whether models based on in vitro/in vivo RBE data
      can be used to predict human response to treatments is an open issue. In this
      work an alternative method, based on an effective radiobiological
      parameterization directly derived from clinical data, is presented. The method
      has been applied to the analysis of prostate cancer trials with protons and
      carbon ions.Prostate cancer trials with proton and carbon ion beams reporting 5
      year-local control (LC5) and grade 2 (G2) or higher genitourinary toxicity rates
      (TOX) were selected from literature to test the method. Treatment simulations
      were performed on a representative subset of patients to produce dose and linear
      energy transfer distribution, which were used as explicative physical variables
      for the radiobiological modelling. Two models were taken into consideration: the
      microdosimetric kinetic model (MKM) and a linear model (LM). The radiobiological
      parameters of the LM and MKM were obtained by coupling them with the tumor
      control probability and normal tissue complication probability models to fit the
      LC5 and TOX data through likelihood maximization. The model ranking was based on
      the Akaike information criterion.Results showed large confidence intervals due to
      the limited variety of available treatment schedules. RBE values, such as RBE =
      1.1 for protons in the treated volume, were derived as a by-product of the
      method, showing a consistency with current approaches. Carbon ion RBE values were
      also derived, showing lower values than those assumed for the original treatment
      planning in the target region, whereas higher values were found in the bladder.
      Most importantly, this work shows the possibility to infer the radiobiological
      parametrization for proton and carbon ion treatment directly from clinical data.

PMID- 25386877
TI  - Facile synthesis of Ba(1-x)K(x)Fe2As2 superconductors via hydride route.
AB  - We have developed a fast, easy, and scalable synthesis method for Ba(1
      x)K(x)Fe2As2 (0 <= x <= 1) superconductors using hydrides BaH2 and KH as a source
      of barium and potassium metals. Synthesis from hydrides provides better mixing
      and easier handling of the starting materials, consequently leading to faster
      reactions and/or lower synthesis temperatures. The reducing atmosphere provided
      by the evolved hydrogen facilitates preparation of oxygen-free powders. By a
      combination of methods we have shown that Ba(1-x)K(x)Fe2As2 obtained via hydride
      route has the same characteristics as when it is prepared by traditional solid
      state synthesis. Refinement from synchrotron powder X-ray diffraction data
      confirms a linear dependence of unit cell parameters upon K content as well as
      the tetragonal to orthorhombic transition at low temperatures for compositions
      with x < 0.2. Magnetic measurements revealed dome-like dependence of
      superconducting transition temperature Tc upon K content with a maximum of 38 K
      for x close to 0.4. Electron diffraction and high-resolution high-angle annular
      dark-field scanning transmission electron microscopy indicates an absence of Ba/K
      ordering, while local inhomogeneity in the Ba/K distribution takes place at a
      scale of several angstroms along [110] crystallographic direction.

PMID- 25386880
TI  - [The screening of the inhibitors of the human cytochrome P450(51) (CYP51A1): the
      plant and animal structural lanosterol's analogs].
AB  - The cholesterol biosynthesis regulation is the important part of the
      hypercholesterolemia diseases therapy. The inhibition of the post-squalene
      cholesterol biosynthesis steps provide the alternative to classic statin therapy.
      Sterol-14a-demethylase (CYP51) is one of the hypothetical targets for it. In this
      work the screening of the ability to interact with human CYP51 (CYP51A1) for the
      nature low-weight compounds with steroid-like scaffold were performed by
      integration of the surface plasmon resonance biosensor and spectral titration
      methods. The results of the selection were 4 compounds (betulafolientriol,
      holothurin A, teasaponin, capsicoside A) witch had high affinity to the CYP51A1
      active site. These data extend the range of compounds which may be used as
      specific inhibitors of CYP51 and give the permission to suggest the dynamic of
      the enzyme. 

PMID- 25386878
TI  - Association of FKBP51 with priming of autophagy pathways and mediation of
      antidepressant treatment response: evidence in cells, mice, and humans.
AB  - BACKGROUND: FK506 binding protein 51 (FKBP51) is an Hsp90 co-chaperone and
      regulator of the glucocorticoid receptor, and consequently of stress physiology.
      Clinical studies suggest a genetic link between FKBP51 and antidepressant
      response in mood disorders; however, the underlying mechanisms remain elusive.
      The objective of this study was to elucidate the role of FKBP51 in the actions of
      antidepressants, with a particular focus on pathways of autophagy. METHODS AND
      FINDINGS: Established cell lines, primary neural cells, human blood cells of
      healthy individuals and patients with depression, and mice were treated with
      antidepressants. Mice were tested for several neuroendocrine and behavioral
      parameters. Protein interactions and autophagic pathway activity were mainly
      evaluated by co-immunoprecipitation and Western blots. We first show that the
      effects of acute antidepressant treatment on behavior are abolished in FKBP51
      knockout (51KO) mice. Autophagic markers, such as the autophagy initiator
      Beclin1, were increased following acute antidepressant treatment in brains from
      wild-type, but not 51KO, animals. FKBP51 binds to Beclin1, changes decisive
      protein interactions and phosphorylation of Beclin1, and triggers autophagic
      pathways. Antidepressants and FKBP51 exhibited synergistic effects on these
      pathways. Using chronic social defeat as a depression-relevant stress model in
      combination with chronic paroxetine (PAR) treatment revealed that the stress
      response, as well as the effects of antidepressants on behavior and autophagic
      markers, depends on FKBP51. In human blood cells of healthy individuals, FKBP51
      levels correlated with the potential of antidepressants to induce autophagic
      pathways. Importantly, the clinical antidepressant response of patients with
      depression (n = 51) could be predicted by the antidepressant response of
      autophagic markers in patient-derived peripheral blood lymphocytes cultivated and
      treated ex vivo (Beclin1/amitriptyline: r = 0.572, p = 0.003; Beclin1/PAR: r =
      0.569, p = 0.004; Beclin1/fluoxetine: r = 0.454, p = 0.026; pAkt/amitriptyline: r
      =  -0.416, p = 0.006; pAkt/PAR: r =  -0.355, p = 0.021; LC3B-II/PAR: r = 0.453, p
      = 0.02), as well as by the lymphocytic expression levels of FKBP51 (r = 0.631,
      p<0.0001), pAkt (r =  -0.515, p = 0.003), and Beclin1 (r = 0.521, p = 0.002) at
      admission. Limitations of the study include the use of male mice only and the
      relatively low number of patients for protein analyses. CONCLUSIONS: To our
      knowledge, these findings provide the first evidence for the molecular mechanism
      of FKBP51 in priming autophagic pathways; this process is linked to the potency
      of at least some antidepressants. These newly discovered functions of FKBP51 also
      provide novel predictive markers for treatment outcome, consistent with
      physiological and potential clinical relevance. Please see later in the article
      for the Editors' Summary.

PMID- 25386879
TI  - A well-resolved phylogeny of the trees of Puerto Rico based on DNA barcode
      sequence data.
AB  - BACKGROUND: The use of phylogenetic information in community ecology and
      conservation has grown in recent years. Two key issues for community
      phylogenetics studies, however, are (i) low terminal phylogenetic resolution and
      (ii) arbitrarily defined species pools. METHODOLOGY/PRINCIPAL FINDINGS: We used
      three DNA barcodes (plastid DNA regions rbcL, matK, and trnH-psbA) to infer a
      phylogeny for 527 native and naturalized trees of Puerto Rico, representing the
      vast majority of the entire tree flora of the island (89%). We used a maximum
      likelihood (ML) approach with and without a constraint tree that enforced
      monophyly of recognized plant orders. Based on 50% consensus trees, the ML
      analyses improved phylogenetic resolution relative to a comparable phylogeny
      generated with Phylomatic (proportion of internal nodes resolved: constrained ML
      = 74%, unconstrained ML = 68%, Phylomatic = 52%). We quantified the phylogenetic
      composition of 15 protected forests in Puerto Rico using the constrained ML and
      Phylomatic phylogenies. We found some evidence that tree communities in areas of
      high water stress were relatively phylogenetically clustered. Reducing the scale
      at which the species pool was defined (from island to soil types) changed some of
      our results depending on which phylogeny (ML vs. Phylomatic) was used. Overall,
      the increased terminal resolution provided by the ML phylogeny revealed
      additional patterns that were not observed with a less-resolved phylogeny.
      CONCLUSIONS/SIGNIFICANCE: With the DNA barcode phylogeny presented here (based on
      an island-wide species pool), we show that a more fully resolved phylogeny
      increases power to detect nonrandom patterns of community composition in several
      Puerto Rican tree communities. Especially if combined with additional information
      on species functional traits and geographic distributions, this phylogeny will
      (i) facilitate stronger inferences about the role of historical processes in
      governing the assembly and composition of Puerto Rican forests, (ii) provide
      insight into Caribbean biogeography, and (iii) aid in incorporating evolutionary
      history into conservation planning.

PMID- 25386881
TI  - [Conjugates of streptavidin with gold nanoparticles for the visualization of dna
      single interactions on the silicon surface].
AB  - The potential of the method of scanning electron microscopy (SEM) to visualize
      the results of individual acts of DNA and oligonucleotides hybridization using
      gold nanoparticles as label was investigated. Molecule of biotin was introduced
      into DNA or oligonucleotide, and then it was detected in DNA duplex using a
      conjugate of streptavidin with gold nanoparticles. Effective imaging of DNA
      duplexes was possible using a conjugate prepared by covalent binding.. The
      detection limit of the model oligonucleotide of 19 bases was 20 pg. 

PMID- 25386882
TI  - [Implementation of scanning probe microscopy for the solution of molecular
      diagnostics tasks].
AB  - We present new approaches to improve the efficiency of DNA by scanning probe
      microscopy using a highly specific hybridization on affine surfaces and
      nanostructures of gold as a labels. Scanning probe microscopy allows to register
      of individual acts of hybridization by the detection of gold labels on the
      surface affinity followed by automatic calculation of the total. 

PMID- 25386883
TI  - [Comparison of basic carboxypeptidases activity in male rats tissues at a single
      injection of haloperidol].
AB  - The influence of a single injection of haloperidol on basic carboxypeptidases
      (biologically active peptide processing enzymes) activity in rat tissues was
      studied. Acute exposure to haloperidol increased the activity of
      carboxypeptidases H (CP H) in hypothalamic-pituitary-adrenal system and
      cerebellum and reduced such activity in testes. Multidirectional changes of PMSF
      inhibited carboxypeptidases activity (PMSF-CP) were observed after a single
      haloperidol injection in all studied tissues except testes. It is suggested that
      changes of CP H and PMSF-CP activity might affect levels of regulatory peptides
      in the brain and blood and thus may be involved in general and side effects of
      haloperidol on the organism. 

PMID- 25386884
TI  - [Biocompatibility of electrospun poly(3-hydroxybutyrate) and its composites
      scaffolds for tissue engineering].
AB  - Development of biodegradable polymers-based scaffolds for tissue engineering is a
      promising trend in bioengineering. The electrospun scaffolds from poly(3
      hydroxybutyrate) (PHB) were produced using different additives that changed the
      physical and chemical characteristics of the products. As a result, the construct
      consisting of interwoven threads of different diameter (0.8-3.4 mm) were
      obtained, the smallest diameter was observed in the threads from the PHB using
      tetrabutilammonium iodide (TBAI) and titanium oxide II (TiO2) as additives.
      Mesenchymal stem cells (MSC) were cultivated on the scaffolds for the
      biocompatibility evaluation of obtained materials. Cells viability was determined
      by the XTT assay test. It was shown that the scaffold from the interwoven threads
      of lowest diameter is most favorable for MSC growth in comparison with the
      polymer film and scaffolds from the threads of larger diameter. Thus, it was
      shown that the biocompatibility of electrospun PHB scaffolds depended on their
      microstructure. The obtained data can be used for development of scaffolds for
      tissue engineering. 

PMID- 25386885
TI  - [Particularities of gamma-aminobutyric acid metabolism in the liver of rats
      during different types of alcohol withdrawal].
AB  - Activities of GABA-catabolising enzymes and the contents of some amino acids have
      been studied in the liver of the rats with different types of alcohol cessation
      after its systemic administration. Intermittent alcohol intoxication was
      accompanied by activation of liver GABA catabolism in case of the lowest alcohol
      load. However ethanol in higher doses and prolongation of intermittent alcohol
      administration decreased GABA catabolism. It is suggested that the observed
      changes may reflect non-specific adaptation of hepatocytes to the excessive
      alcohol consumption and its further cessation. 

PMID- 25386886
TI  - [The role of vitamin D3 in the regulation of the mineral metabolism in
      experimental type 1 diabetes].
AB  - Diabetes was shown to be associated with a considerable lowering of 25(OH)D3 in
      blood serum of mice. Vitamin D3 deficiency was correlated with impaired mineral
      metabolism in bone tissue, indicating the development of secondary osteoporosis.
      A decrease in weight, length and diameter (diaphysis, proximal metaepiphysis) of
      tibia in diabetic animals was observed as compared with control. Diabetes caused
      hypocalcemia, hypophosphatemia and increased enzymatic activity of alkaline
      phosphatase (ALP) and its isoenzymes in serum. This changes were accompanied by
      the impairments of vitamin D3 25-hydroxylase isoforms (CYP27A1 and CYP2R1)
      expression, which are the main enzymes of cholecalciferol biotransformation to
      25(OH)D3 - precursor of hormonally active form of vitamin D3. A decrease in bone
      resorption processes was established after vitamin D3 administration as it is
      evident from normalization of bone morphometrical parameters and mineral
      metabolism in diabetic mice. Vitamin D3 ability to counter diabetes-induced
      alterations in bone tissue can be ascribed, at least in part, to its positive
      effects on the formation of vitamin D3 hormonally active forms. 

PMID- 25386887
TI  - [Effect of 17beta-estradiol on bioenergetic processes in the heart mitochondria
      of ovariectomized rats with insulin resistance].
AB  - The bioenergetic processes in the heart mitochondria of Wistar rats with fructose
      induced insulin resistance was investigated in female animals with different
      estrogen status. Respiration studies on isolated heart mitochondria by the
      polarographic method revealed that estrogen deficiency reduced complex IV
      activity, while its combination with high-fructose diet induced additional
      disturbances in the coupling of respiration and oxidative phosphorylation at the
      level of complex I of the electron transport chain. Exogenous 17b-estradiol
      inhibited the development of mitochondrial dysfunction in cardiomyocytes of
      ovariectomized rats with insulin resistance. 

PMID- 25386888
TI  - [Effect of sulfated polysaccharides from brown seaweed Laminaria japonica on the
      morfology of lymfoid organs and functional characteristics of immunocompetent
      cells].
AB  - The effect of sulfated polysaccharide fucoidan from the brown alga Laminaria
      japonica on morphological characteristics of mouse lymphoid organs,
      subpopulations of spleen mononuclear leukocytes, cytokine production and
      cytotoxic activity of splenocytes has been investigated. Fucoidan promoted
      activation and proliferation of lymphoid hematopoietic cells in primary and
      secondary immunogenesis bodies, increased expression of markers CD19, NK, NKT,
      CD25, MHC II, TCR, TLR2 and TLR4, the cytotoxic activity of splenocytes and
      production of immunoregulatory and proinflammatory cytokines (IL- 2, IL-12, IFN
      g, TNF-a, IL-6). This suggests activation of effector mechanisms of innate
      immunity and adaptive immune responses via the Th-1 type. 

PMID- 25386889
TI  - [Blood acid-base balance of sportsmen during physical activity].
AB  - The aim of this study was to investigate the acid-base balance parameters in
      blood of sportsmen by physical activity. Before exercise lactate concentration in
      blood was normal. Carbon dioxide pressure (rSO2), bicarbonate concentration (NSO3
      -), base excess (BE), were increased immediately after physical activity lactate
      concentration increased, while pH, BE, NSO3 -, rSO2 decreased in capillary blood
      of sportsmen. These changes show the development of lactate-acidosis which is
      partly compensated with bicarbonate buffering system and respiratory alkalosis.
      During postexercise recovery lactate concentration decreased, while rSO2, NSO3 -,
      BE increased. The results of this study can be used for diagnostics of acid-base
      disorders and their medical treatment for preservation of sportsmen physical
      capacity. 

PMID- 25386890
TI  - [Imbalance of system of glutamin - glutamic acid in the placenta and amniotic
      fluid at placental insufficiency].
AB  - Metabolism of glutamine and glutamic acid has been investigated in the placenta
      and amniotic fluid under conditions of placental insufficiency. The development
      of placental insufficiency is characterized by the increased content of glutamic
      acid and a decrease of glutamine in both placenta and amniotic fluid. These
      changes changes were accompanied by changes in the activity of enzymes involved
      in the metabolism of these amino acids. There was a decrease in glutamate
      dehydrogenase activity and an increase in glutaminase activity with the
      simultaneous decrease of glutamine synthetase activity. The compensatory decrease
      in the activity of glutamine keto acid aminotransferase did not prevent a
      decrease in the glutamine level. The impairments in the system glutamic acid
      glutamine were more pronounced during the development of premature labor. 

PMID- 25386891
TI  - [Extracting and study of biochemical properties of thiamine pyrophosphokinase
      from non-malignant and tumor tissue of myometrium].
AB  - The method of extraction and purification of thiamine pyrophosphokinase from non
      malignant and tumor tissue of myometrium has been elaborated. Kinetic
      characteristics of T-kinase from non-malignant and tumor tissue of women
      myometrium have been studied. It has been shown, that malignization of myometrium
      is accompanied by a decrease in affinity of thiamine pyrophosphokinase from tumor
      to thiamine and by an increase in sensitivity of the enzyme from tumor to
      thiochrome. 

PMID- 25386893
TI  - Vitamin D and infectious diseases.
AB  - In the early 1920s the antirachitic effect of food irradiated with ultraviolet
      light and cod liver oil has been recognized. The antirachitic substance was
      identified and called "vitamin D". Since then the key role of vitamin D in
      calcium and bone homeostasis has been investigated. Moreover, it has been
      recognized that vitamin D is able to modulate a variety of processes and
      regulatory systems such as host defense, inflammation, immunity, and repair.
      According to recent studies, vitamin D deficiency is likely to be an important
      etiological factor in the pathogenesis of many chronic diseases, as well as it
      has been associated with higher mortality rate for respiratory disease. In this
      regard, either observational studies aimed to verify an association between low
      vitamin D level and the incidence of respiratory tract infections (RTIs) or
      clinical trials on the effect of vitamin D as a supplementary treatment in RTIs
      patients have been presented in the emerging clinical literature. Conflicting
      results have been demonstrated in several randomized, double-blind, placebo
      controlled trials concerning the vitamin D treatment in tuberculosis. Some
      studies suggest a beneficial effect by vitamin D but it could not be reproduced
      in larger studies so far. In conclusion, although basic science research suggests
      that vitamin D may play an important role in modulating immune functions, no
      strong evidence exists whether correction of vitamin D depletion may be useful in
      the prevention or treatment of infections. Further and larger studies may clarify
      the role of vitamin D in infection.

PMID- 25386892
TI  - Hydroxyapatite-coated sillicone rubber enhanced cell adhesion and it may be
      through the interaction of EF1beta and gamma-actin.
AB  - Silicone rubber (SR) is a common soft tissue filler material used in plastic
      surgery. However, it presents a poor surface for cellular adhesion and suffers
      from poor biocompatibility. In contrast, hydroxyapatite (HA), a prominent
      component of animal bone and teeth, can promote improved cell compatibility, but
      HA is an unsuitable filler material because of the brittleness in mechanism. In
      this study, using a simple and economical method, two sizes of HA was applied to
      coat on SR to counteract the poor biocompatibility of SR. Surface and mechanical
      properties of SR and HA/SRs confirmed that coating with HA changes the surface
      topology and material properties. Analysis of cell proliferation and adhesion as
      well as measurement of the expression levels of adhesion related molecules
      indicated that HA-coated SR significantly increased cell compatibility.
      Furthermore, mass spectrometry proved that the biocompatibility improvement may
      be related to elongation factor 1-beta (EF1beta)/gamma-actin adjusted
      cytoskeletal rearrangement. 

PMID- 25386894
TI  - Charging and softening, collapse, and crystallization of dipolar phospholipid
      membranes by aqueous ionic liquid solutions.
AB  - Ionic liquids have a variety of unique controllable structures and properties.
      These properties may be used to tailor the self-assembly of charged and dipolar
      biomolecules. Using solution X-ray scattering, we measured the structure of
      Dilauryl(C12:0)-sn-glycero-3-phospho-l-choline (DLPC), a dipolar (or
      zwitterionic) lipid, in the water-soluble room temperature ionic liquid Ethyl
      Methyl Imidazolium Ethyl Sulfate (EMIES) and mixtures of EMIES and water. We find
      that the interaction between the lipid bilayers is dominated by the balance
      between the charging of the polar headgroups by the ionic liquid, softening of
      the bilayer, and the osmotic pressure induced by the solvent. This balance leads
      to the following changes with increasing ionic liquid concentration: an
      incomplete unbinding transition from an attractive regime to a swollen regime of
      the lamellar phase formed by the bilayers. The swollen phase is followed by a
      collapse of the bilayers into a highly desolvated lamellar phase at some critical
      EMIES concentration, and eventually formation of lipid-crystalline phase, at very
      high EMIES concentrations. The latter phase is revealed by wide-angle X-ray
      scattering (WAXS) from the lipid solutions, showing multiple Bragg peaks,
      consistent with highly ordered structures. These structures were not observed in
      any other type of aqueous solutions containing monovalent or multivalent ions.
      The kinetics and temperature dependence of these transitions were also
      determined. 

PMID- 25386895
TI  - Student journals: a means of assessing transformative learning in aging related
      courses.
AB  - In courses where topics are sensitive or even considered taboo for discussion, it
      can be difficult to assess students' deeper learning. In addition, incorporating
      a wide variety of students' values and beliefs, designing instructional
      strategies and including varied assessments adds to the difficulty. Journal
      entries or response notebooks can highlight reflection upon others' viewpoints,
      class readings, and additional materials. These are useful across all educational
      levels in deep learning and comprehension strategies assessments. Journaling
      meshes with transformative learning constructs, allowing for critical self
      reflection essential to transformation. Qualitative analysis of journals in a
      death and dying class reveals three transformative themes: awareness of others,
      questioning, and comfort. Students' journal entries demonstrate transformative
      learning via communication with others through increased knowledge/exposure to
      others' experiences and comparing/contrasting others' personal beliefs with their
      own. Using transformative learning within gerontology and geriatrics education,
      as well as other disciplined aging-related courses is discussed. 

PMID- 25386896
TI  - CD148 tyrosine phosphatase promotes cadherin cell adhesion.
AB  - CD148 is a transmembrane tyrosine phosphatase that is expressed at cell
      junctions. Recent studies have shown that CD148 associates with the
      cadherin/catenin complex and p120 catenin (p120) may serve as a substrate.
      However, the role of CD148 in cadherin cell-cell adhesion remains unknown.
      Therefore, here we addressed this issue using a series of stable cells and cell
      based assays. Wild-type (WT) and catalytically inactive (CS) CD148 were
      introduced to A431D (lacking classical cadherins), A431D/E-cadherin WT
      (expressing wild-type E-cadherin), and A431D/E-cadherin 764AAA (expressing p120
      uncoupled E-cadherin mutant) cells. The effects of CD148 in cadherin adhesion
      were assessed by Ca2+ switch and cell aggregation assays. Phosphorylation of E
      cadherin/catenin complex and Rho family GTPase activities were also examined.
      Although CD148 introduction did not alter the expression levels and complex
      formation of E-cadherin, p120, and beta-catenin, CD148 WT, but not CS, promoted
      cadherin contacts and strengthened cell-cell adhesion in A431D/E-cadherin WT
      cells. This effect was accompanied by an increase in Rac1, but not RhoA and
      Cdc42, activity and largely diminished by Rac1 inhibition. Further, we
      demonstrate that CD148 reduces the tyrosine phosphorylation of p120 and beta
      catenin; causes the dephosphorylation of Y529 suppressive tyrosine residue in
      Src, a well-known CD148 site, increasing Src activity and enhancing the
      phosphorylation of Y228 (a Src kinase site) in p120, in E-cadherin contacts.
      Consistent with these findings, CD148 dephosphorylated both p120 and beta-catenin
      in vitro. The shRNA-mediated CD148 knockdown in A431 cells showed opposite
      effects. CD148 showed no effects in A431D and A431D/E-cadherin 764AAA cells. In
      aggregate, these findings provide the first evidence that CD148 promotes E
      cadherin adhesion by regulating Rac1 activity concomitant with modulation of
      p120, beta-catenin, and Src tyrosine phosphorylation. This effect requires E
      cadherin and p120 association. 

PMID- 25386898
TI  - Intent to fail: significance testing of forced choice test results.
AB  - A score that is significantly below the level of chance on a forced choice (FC)
      performance validity test results from the deliberate production of wrong
      answers. In order to increase the power of significance testing of a below chance
      result on standardized FC tests with empirically derived cutoff scores, we
      recommend using one-tailed tests of significance and selecting probability levels
      greater than .05 (.20 for most standardized FC tests with empirically derived
      cutoff scores). Under certain circumstances, we also recommend combining scores
      from different sections of the same FC test and combining scores across different
      FC tests. These recommendations require modifications when applied to non
      standardized FC tests that lack empirically derived cutoff scores or to FC tests
      with a non-random topographical distribution of correct and incorrect answers. 

PMID- 25386897
TI  - Effects of vaccination on invasive pneumococcal disease in South Africa.
AB  - BACKGROUND: In South Africa, a 7-valent pneumococcal conjugate vaccine (PCV7) was
      introduced in 2009 with a three-dose schedule for infants at 6, 14, and 36 weeks
      of age; a 13-valent vaccine (PCV13) replaced PCV7 in 2011. In 2012, it was
      estimated that 81% of 12-month-old children had received three doses of vaccine.
      We assessed the effect of vaccination on invasive pneumococcal disease. METHODS:
      We conducted national, active, laboratory-based surveillance for invasive
      pneumococcal disease. We calculated the change in the incidence of the disease
      from a prevaccine (baseline) period (2005 through 2008) to postvaccine years 2011
      and 2012, with a focus on high-risk age groups. RESULTS: Surveillance identified
      35,192 cases of invasive pneumococcal disease. The rates among children younger
      than 2 years of age declined from 54.8 to 17.0 cases per 100,000 person-years
      from the baseline period to 2012, including a decline from 32.1 to 3.4 cases per
      100,000 person-years in disease caused by PCV7 serotypes (-89%; 95% confidence
      interval [CI], -92 to -86). Among children not infected with the human
      immunodeficiency virus (HIV), the estimated incidence of invasive pneumococcal
      disease caused by PCV7 serotypes decreased by 85% (95% CI, -89 to -79), whereas
      disease caused by nonvaccine serotypes increased by 33% (95% CI, 15 to 48). Among
      adults 25 to 44 years of age, the rate of PCV7-serotype disease declined by 57%
      (95% CI, -63 to -50), from 3.7 to 1.6 cases per 100,000 person-years.
      CONCLUSIONS: Rates of invasive pneumococcal disease among children in South
      Africa fell substantially by 2012. Reductions in the rates of disease caused by
      PCV7 serotypes among both children and adults most likely reflect the direct and
      indirect effects of vaccination. (Funded by the National Institute for
      Communicable Diseases of the National Health Laboratory Service and others.).

PMID- 25386900
TI  - Aqueous transition-metal cations as impurities in a wide gap oxide: the
      Cu(2+)/Cu(+) and Ag(2+)/Ag(+) redox couples revisited.
AB  - The interactions of the d electrons of transition-metal aqua ions with the
      solvent are usually divided in short-range electronic interactions with ligand
      water molecules and long-range electrostatic interactions with molecules beyond
      the first coordination shell. This is the rationale behind the cluster continuum
      and QM/MM methods developed for the computation of the redox potentials. In the
      density functional theory based molecular dynamics (DFTMD) method, the electronic
      states of the complex are also allowed to mix with the extended band states of
      the solvent. Returning to the Cu(+) and Ag(+) oxidation reaction, which has been
      the subject of DFTMD simulation before, we show that coupling to the valence band
      states of water is greatly enhanced by the band gap error in the density
      functional approximation commonly used in DFTMD (the generalized gradient
      approximation). This effect is analyzed by viewing the solvent as a wide gap
      oxide and the redox active ions as electronic defects. The errors can be reduced
      significantly by application of hybrid functionals containing a fraction of
      Hartree-Fock exchange. These calculations make use of recent progress in DFTMD
      technology, enabling us to include sp core polarization and Hartree-Fock exchange
      in condensed-phase model systems. 

PMID- 25386899
TI  - Parent-targeted mobile phone intervention to increase physical activity in
      sedentary children: randomized pilot trial.
AB  - BACKGROUND: Low levels of moderate-to-vigorous physical activity are associated
      with adverse health consequences. OBJECTIVE: The intent of the study was to
      determine the feasibility and efficacy of a 12-week physical activity promotion
      program targeting children, which was delivered to parents through mobile phones.
      METHODS: Potential participants were recruited through advertisements placed in
      the newspaper, local hospitals and schools, and an email listserv. Sedentary
      children aged 6-10 years were randomly assigned to a minimal (MIG) or intensive
      (IIG) intervention group. Parents in the MIG were given a goal to increase
      (within 1 month) and maintain their child's activity at 6000 pedometer steps/day
      above their baseline levels and to monitor their child's steps daily. Parents in
      the IIG were given the same steps/day and monitoring goals, in addition to text
      messages and articles containing additional behavioral strategies (based on the
      Social Cognitive Theory) designed to promote their child's physical activity. The
      intervention components were delivered via mobile phone. Anthropometrics, body
      composition, and questionnaires were administered in a clinic. Children wore a
      New Lifestyles pedometer (NL-1000) each day throughout the intervention and
      parents were to monitor their child's step counts daily. RESULTS: Out of 59
      children who screened for the study, a total of 27 children (mean age 8.7, SD 1.4
      years; 56%, 15/27 female; 59%, 16/27 African American) were enrolled and
      completed the study. Overall, 97.90% (2220/2268; 98.20%, 1072/1092 for MIG;
      97.60%, 1148/1176 for IIG) of expected step data were successfully entered by the
      parent or study coordinator. Parents in the MIG and IIG were sent approximately 7
      and 13 text messages per week, respectively, averaged over the course of the
      study. IIG parents accessed an average of 6.1 (SD 4.4) articles over the course
      of the intervention and accessed a fewer number of articles in the last month
      compared to the first 2 months of the study (P=.002). Children in both the MIG
      and IIG significantly increased their physical activity, averaged over 12 weeks,
      by 1427.6 (SD 583.0; P=.02) and 2832.8 (SD 604.9; P<.001) steps/day above
      baseline, respectively. The between group difference was not statistically
      significant (P=.10; effect size=.40), nor was the group by time interaction
      (P=.57). Regardless of group assignment, children who significantly increased
      their physical activity reported greater increases in physical activity enjoyment
      (P=.003). The number of behavioral articles accessed by IIG parents was
      significantly correlated with change in children's steps/day (r=.575, P=.04).
      Changes in children's steps/day were unrelated to changes in their body
      composition, mood, and food intake. CONCLUSIONS: Parent-targeted mobile phone
      interventions are feasible, yet more intense interventions may be needed to
      support parents' efforts to increase their children's physical activity to levels
      that approximate national recommendations. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01551108; http://clinicaltrials.gov/show/NCT01551108 (Archived by WebCite at
      http://www.webcitation.org/6TNEOzXNX).

PMID- 25386901
TI  - Giving or receiving something for sex: a cross-sectional study of transactional
      sex among Ugandan university students.
AB  - OBJECTIVE: This study sought to determine the prevalence of transactional sex
      among university students in Uganda and to assess the possible relationship
      between transactional sex and sexual coercion, physical violence, mental health,
      and alcohol use. METHODS: In 2010, 1954 undergraduate students at a Ugandan
      university responded to a self-administered questionnaire that assessed mental
      health, substance use, physical violence and sexual behaviors including sexual
      coercion and transactional sex. The prevalence of transactional sex was assessed
      and logistic regression analysis was performed to measure the associations
      between various risk factors and reporting transactional sex. RESULTS:
      Approximately 25% of the study sample reported having taken part in transactional
      sex, with more women reporting having accepted money, gifts or some compensation
      for sex, while more men reporting having paid, given a gift or otherwise
      compensated for sex. Sexual coercion in men and women was significantly
      associated with having accepted money, gifts or some compensation for sex. Men
      who were victims of physical violence in the last 12 months had higher
      probability of having accepted money, gifts or some compensation for sex than
      other men. Women who were victims of sexual coercion reported greater likelihood
      of having paid, given a gift or otherwise compensated for sex. Respondents who
      had been victims of physical violence in last 12 months, engaged in heavy
      episodic drinking and had poor mental health status were more likely to have
      paid, given a gift or otherwise compensated for sex. CONCLUSIONS: University
      students in Uganda are at high risk of transactional sex. Young men and women may
      be equally vulnerable to the risks and consequences of transactional sex and
      should be included in program initiatives to prevent transactional sex. The role
      of sexual coercion, physical violence, mental health, and alcohol use should be
      considered when designing interventions for countering transactional sex.

PMID- 25386902
TI  - Label-retaining stromal cells in mouse endometrium awaken for expansion and
      repair after parturition.
AB  - Human and mouse endometrium undergo dramatic cellular reorganization during
      pregnancy and postpartum. Somatic stem cells maintain homeostasis of the tissue
      by providing a cell reservoir for regeneration. We hypothesized that endometrial
      cells with quiescent properties (stem/progenitor cells) were involved in the
      regeneration of the endometrial tissue. Given that stem cells divide
      infrequently, they can retain the DNA synthesis label [bromodeoxyuridine (BrdU)]
      after a prolonged chase period. In this study, prepubertal mice were pulsed with
      BrdU and after a 6-week chase a small population of label-retaining stromal cells
      (LRSC) was located primarily beneath the luminal epithelium, adjacent to blood
      vessels, and near the endometrial-myometrial junction. Marker analyses suggested
      that they were of mesenchymal origin expressing CD44(+), CD90(+), CD140b(+),
      CD146(+), and Sca-1(+). During pregnancy, nonproliferating LRSC predominately
      resided at the interimplantation/placental loci of the gestational endometrium.
      Immediately after parturition, a significant portion of the LRSC underwent
      proliferation (BrdU(+)/Ki-67(+)) and expressed total and active beta-catenin. The
      beta-catenin expression in the LRSC was transiently elevated at postpartum day
      (PPD) 1. The proliferation of LRSC resulted in a significant decline in the
      proportion of LRSC in the postpartum uterus. The LRSC returned to dormancy at
      PPD7, and the percentage of LRSC remained stable thereafter until 11 weeks. This
      study demonstrated that LRSC can respond efficiently to physiological stimuli
      upon initiation of uterine involution and return to its quiescent state after
      postpartum repair. 

PMID- 25386903
TI  - Advanced glycation endproducts interfere with adhesion and neurite outgrowth.
AB  - Advanced glycation endproducts (AGEs) represent a non-enzymatic posttranslational
      protein modification. AGEs are generated by a series of chemical reactions of
      free reducing monosaccharides, such as glucose, fructose or metabolites of the
      monosaccharide metabolism with amino groups of proteins. After oxidation,
      dehydration and condensation, stable AGE-modifications are formed. AGE-modified
      proteins accumulate in all cells and tissues as a normal feature of ageing and
      correlate with the glucose concentration in the blood. AGEs are increased in
      diabetic patients and play a significant role in the pathogenesis of most age
      related neural disorders, such as Alzheimer's disease. We examined the role of
      AGEs on neurite outgrowth of PC12 cells. We induced the formation of AGEs using
      the reactive carbonyl compound methylglyoxal (MGO) as a physiological metabolite
      of glucose. We found that AGE-modification of laminin or collagen interfered with
      adhesion but not with neurite outgrowth of PC12 cells. Furthermore, the AGE
      modification of PC12 cell proteins reduced NGF-induced neurite outgrowth. In
      conclusion, our data show that AGEs negatively influence neural plasticity. 

PMID- 25386904
TI  - Alcohol Consumption and the Risk for Developing Pancreatitis: A Case-Control
      Study in Japan.
AB  - OBJECTIVE: This study aimed to estimate the association of alcohol consumption
      and pancreatitis in Japan. METHODS: We performed a nationwide case-control study,
      which included 982 patients (574 patients with acute pancreatitis and 408
      patients with chronic pancreatitis) and 1015 controls who were individually
      matched for sex, age, hospital, and time of their first hospital visit.
      Conditional logistic regression was used to assess the association of alcohol
      consumption and smoking with pancreatitis. RESULTS: The patients had a mean (SD)
      age of 57.6 (17.0) years; 71.8% were male. Compared with nondrinkers, alcohol
      consumption of less than 20 g/d was not associated with the risk for total
      pancreatitis (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.7-1.4). In
      patients with acute pancreatitis, the ORs (95% CI) for alcohol consumption of 20
      <= ~ < 40 g/d, 40 <= ~ < 60 g/d, 60 <= ~ < 80 g/d, 80 <= ~ < 100 g/d, and 100 g/d
      or greater were 1.7 (0.9-3.0), 3.1 (1.6-5.9), 4.2 (2.1-8.2), 5.3 (2.4-12.0), and
      6.4 (3.4-12.4), respectively. In patients with chronic pancreatitis, the ORs (95%
      CI) for alcohol consumption of 20 <= ~ < 40 g/d, 40 <= ~ < 60 g/d, 60 <= ~ < 80
      g/d, 80 <= ~ < 100 g/d, and 100 g/d or greater were 2.6 (1.2-5.5), 3.2 (1.5-7.1),
      9.2 (4.1-20.3), 13.0 (5.3-31.6), and 19.6 (8.2-46.8), respectively. CONCLUSIONS:
      Our study precisely measured the quantitative effect of alcohol on the risk for
      developing pancreatitis.

PMID- 25386905
TI  - Thoughts of death modulate psychophysical and cortical responses to threatening
      stimuli.
AB  - Existential social psychology studies show that awareness of one's eventual death
      profoundly influences human cognition and behaviour by inducing defensive
      reactions against end-of-life related anxiety. Much less is known about the
      impact of reminders of mortality on brain activity. Therefore we explored whether
      reminders of mortality influence subjective ratings of intensity and threat of
      auditory and painful thermal stimuli and the associated electroencephalographic
      activity. Moreover, we explored whether personality and demographics modulate
      psychophysical and neural changes related to mortality salience (MS). Following
      MS induction, a specific increase in ratings of intensity and threat was found
      for both nociceptive and auditory stimuli. While MS did not have any specific
      effect on nociceptive and auditory evoked potentials, larger amplitude of theta
      oscillatory activity related to thermal nociceptive activity was found after
      thoughts of death were induced. MS thus exerted a top-down modulation on theta
      electroencephalographic oscillatory amplitude, specifically for brain activity
      triggered by painful thermal stimuli. This effect was higher in participants
      reporting higher threat perception, suggesting that inducing a death-related mind
      set may have an influence on body-defence related somatosensory representations. 

PMID- 25386906
TI  - NET23/STING promotes chromatin compaction from the nuclear envelope.
AB  - Changes in the peripheral distribution and amount of condensed chromatin are
      observed in a number of diseases linked to mutations in the lamin A protein of
      the nuclear envelope. We postulated that lamin A interactions with nuclear
      envelope transmembrane proteins (NETs) that affect chromatin structure might be
      altered in these diseases and so screened thirty-one NETs for those that promote
      chromatin compaction as determined by an increase in the number of chromatin
      clusters of high pixel intensity. One of these, NET23 (also called STING, MITA,
      MPYS, ERIS, Tmem173), strongly promoted chromatin compaction. A correlation
      between chromatin compaction and endogenous levels of NET23/STING was observed
      for a number of human cell lines, suggesting that NET23/STING may contribute
      generally to chromatin condensation. NET23/STING has separately been found to be
      involved in innate immune response signaling. Upon infection cells make a choice
      to either apoptose or to alter chromatin architecture to support focused
      expression of interferon genes and other response factors. We postulate that the
      chromatin compaction induced by NET23/STING may contribute to this choice because
      the cells expressing NET23/STING eventually apoptose, but the chromatin
      compaction effect is separate from this as the condensation was still observed
      when cells were treated with Z-VAD to block apoptosis. NET23/STING-induced
      compacted chromatin revealed changes in epigenetic marks including changes in
      histone methylation and acetylation. This indicates a previously uncharacterized
      nuclear role for NET23/STING potentially in both innate immune signaling and
      general chromatin architecture. 

PMID- 25386907
TI  - Transfer of maternal antibodies against avian influenza virus in mallards (Anas
      platyrhynchos).
AB  - Maternal antibodies protect chicks from infection with pathogens early in life
      and may impact pathogen dynamics due to the alteration of the proportion of
      susceptible individuals in a population. We investigated the transfer of maternal
      antibodies against avian influenza virus (AIV) in a key AIV host species, the
      mallard (Anas platyrhynchos). Combining observations in both the field and in
      mallards kept in captivity, we connected maternal AIV antibody concentrations in
      eggs to (i) female body condition, (ii) female AIV antibody concentration, (iii)
      egg laying order, (iv) egg size and (v) embryo sex. We applied maternity analysis
      to the eggs collected in the field to account for intraspecific nest parasitism,
      which is reportedly high in Anseriformes, detecting parasitic eggs in one out of
      eight clutches. AIV antibody prevalence in free-living and captive females was
      respectively 48% and 56%, with 43% and 24% of the eggs receiving these antibodies
      maternally. In both field and captive study, maternal AIV antibody concentrations
      in egg yolk correlated positively with circulating AIV antibody concentrations in
      females. In the captive study, yolk AIV antibody concentrations correlated
      positively with egg laying order. Female body mass and egg size from the field
      and captive study, and embryos sex from the field study were not associated with
      maternal AIV antibody concentrations in eggs. Our study indicates that maternal
      AIV antibody transfer may potentially play an important role in shaping AIV
      infection dynamics in mallards. 

PMID- 25386908
TI  - The feasibility of the interferon gamma release assay and predictors of
      discordance with the tuberculin skin test for the diagnosis of latent
      tuberculosis infection in a remote Aboriginal community.
AB  - BACKGROUND: The tuberculin skin test (TST) is the standard test used to screen
      for latent TB infection (LTBI) in the northern Canadian territory of Nunavut.
      Interferon gamma release assays (IGRA) are T cell blood-based assays to diagnose
      LTBI. The Bacillus Calmette-Guerin (BCG) vaccine is part of the routine
      immunization schedule in Nunavut. The objective of this study was to test the
      feasibility, and predictors of discordance between the Tuberculin Skin Test (TST)
      and the IGRA assay in a medically under-serviced remote arctic Aboriginal
      population. METHODS: Both the TST and QuantiFERON-TB Gold (Qiagen group) IGRA
      tests were offered to people in their homes as part of a public health campaign
      aimed at high TB risk residential areas in Iqaluit, Nunavut, Canada. Feasibility
      was measured by the capacity of the staff to do the test successfully as measured
      by the proportion of results obtained. RESULTS: In this population of
      predominantly young Inuit who were mostly BCG vaccinated, the use of IGRA for the
      diagnosis of LTBI was feasible. IGRA testing resulted in more available test
      results reaching patients (95.6% vs 90.9% p = 0.02) but took longer (median 8
      days (IGRA) vs 2 days (TST), p value < 0.0001). 44/256 participants (17.2%) had
      discordant results. Multivariable regression analysis suggested that discordant
      results were most likely to have received multiple BCG vaccinations (RR 20.03,
      95% CI, 3.94-101.82)), followed by BCG given post infancy (RR 8.13, 95% CI, 2.54
      26.03)) and then to a lesser degree when BCG was given in infancy (RR 6.43, 95%
      CI, 1.72-24.85). INTERPRETATION: IGRA is feasible in Iqaluit, Nunavut, a remote
      Arctic community. IGRA testing results in more test results available to patients
      compared to TST. This test could result in fewer patients requiring latent TB
      treatment among those previously vaccinated with BCG in a region with limited
      public health human resources.

PMID- 25386909
TI  - Analysis of the changes in keratoplasty indications and preferred techniques.
AB  - BACKGROUND: Recently, novel techniques introduced to the field of corneal
      surgery, e.g. Descemet membrane endothelial keratoplasty (DMEK) and corneal
      crosslinking, extended the therapeutic options. Additionally contact lens fitting
      has developed new alternatives. We herein investigated, whether these techniques
      have affected volume and spectrum of indications of keratoplasties in both a
      center more specialized in treating Fuchs' dystrophy (center 1) and a second
      center that is more specialized in treating keratoconus (center 2). METHODS: We
      retrospectively reviewed the waiting lists for indication, transplantation
      technique and the patients' travel distances to the hospital at both centers.
      RESULTS: We reviewed a total of 3778 procedures. Fuchs' dystrophy increased at
      center 1 from 17% (42) to 44% (150) and from 13% (27) to 23% (62) at center 2. In
      center 1, DMEK increased from zero percent in 2010 to 51% in 2013. In center 2,
      DMEK was not performed until 2013. The percentage of patients with keratoconus
      slightly decreased from 15% (36) in 2009 vs. 12% (40) in 2013 in center 1. The
      respective percentages in center 2 were 28% (57) and 19% (51). In both centers,
      the patients' travel distances increased. CONCLUSIONS: The results from center 1
      suggest that DMEK might increase the total number of keratoplasties. The increase
      in travel distance suggests that this cannot be fully attributed to recruiting
      the less advanced patients from the hospital proximity. The increase is rather
      due to more referrals from other regions. The decrease of keratoconus patients in
      both centers is surprising and may be attributed to optimized contact lens
      fitting or even to the effect corneal crosslinking procedure.

PMID- 25386910
TI  - Timing of the departure of ocean biogeochemical cycles from the preindustrial
      state.
AB  - Changes in ocean chemistry and climate induced by anthropogenic CO2 affect a
      broad range of ocean biological and biogeochemical processes; these changes are
      already well underway. Direct effects of CO2 (e.g. on pH) are prominent among
      these, but climate model simulations with historical greenhouse gas forcing
      suggest that physical and biological processes only indirectly forced by CO2 (via
      the effect of atmospheric CO2 on climate) begin to show anthropogenically-induced
      trends as early as the 1920s. Dates of emergence of a number of representative
      ocean fields from the envelope of natural variability are calculated for global
      means and for spatial 'fingerprints' over a number of geographic regions.
      Emergence dates are consistent among these methods and insensitive to the exact
      choice of regions, but are generally earlier with more spatial information
      included. Emergence dates calculated for individual sampling stations are more
      variable and generally later, but means across stations are generally consistent
      with global emergence dates. The last sign reversal of linear trends calculated
      for periods of 20 or 30 years also functions as a diagnostic of emergence, and is
      generally consistent with other measures. The last sign reversal among 20 year
      trends is found to be a conservative measure (biased towards later emergence),
      while for 30 year trends it is found to have an early emergence bias, relative to
      emergence dates calculated by departure from the preindustrial mean. These
      results are largely independent of emission scenario, but the latest-emerging
      fields show a response to mitigation. A significant anthropogenic component of
      ocean variability has been present throughout the modern era of ocean
      observation. 

PMID- 25386911
TI  - OsARF16 is involved in cytokinin-mediated inhibition of phosphate transport and
      phosphate signaling in rice (Oryza sativa L.).
AB  - BACKGROUND: Plant responses to phytohormone stimuli are the most important
      biological features for plants to survive in a complex environment. Cytokinin
      regulates growth and nutrient homeostasis, such as the phosphate (Pi) starvation
      response and Pi uptake in plants. However, the mechanisms underlying how
      cytokinin participates in Pi uptake and Pi signaling are largely unknown. In this
      study, we found that OsARF16 is required for the cytokinin response and is
      involved in the negative regulation of Pi uptake and Pi signaling by cytokinin.
      PRINCIPAL FINDINGS: The mutant osarf16 showed an obvious resistance to exogenous
      cytokinin treatment and the expression level of the OsARF16 gene was considerably
      up-regulated by cytokinin. Cytokinin (6-BA) application suppressed Pi uptake and
      the Pi starvation response in wild-type Nipponbare (NIP) and all these responses
      were compromised in the osarf16 mutant. Our data showed that cytokinin inhibits
      the transport of Pi from the roots to the shoots and that OsARF16 is involved in
      this process. The Pi content in the osarf16 mutant was much higher than in NIP
      under 6-BA treatment. The expressions of PHOSPHATE TRANSPORTER1 (PHT1) genes,
      phosphate (Pi) starvation-induced (PSI) genes and purple PAPase genes were higher
      in the osarf16 mutant than in NIP under cytokinin treatment. CONCLUSION: Our
      results revealed a new biological function for OsARF16 in the cytokinin-mediated
      inhibition of Pi uptake and Pi signaling in rice.

PMID- 25386912
TI  - Reactivity of liquid and semisolid secondary organic carbon with chloride and
      nitrate in atmospheric aerosols.
AB  - Constituents of secondary organic carbon (SOC) in atmospheric aerosols are often
      mixed with inorganic components and compose a significant mass fraction of fine
      particulate matter in the atmosphere. Interactions between SOC and other
      condensed-phase species are not well understood. Here, we investigate the
      reactions of liquid-like and semisolid SOC from ozonolysis of limonene (LSOC) and
      alpha-pinene (PSOC) with NaCl using a set of complementary microspectroscopic
      analyses. These reactions result in chloride depletion in the condensed phase,
      release of gaseous HCl, and formation of organic salts. The reactions attributed
      to acid displacement by SOC acidic components are driven by the high volatility
      of HCl. Similar reactions can take place in SOC/NaNO3 particles. The results show
      that an increase in SOC mass fraction in the internally mixed SOC/NaCl particles
      leads to higher chloride depletion. Glass transition temperatures and viscosity
      of PSOC were estimated for atmospherically relevant conditions. Data show that
      the reaction extent depends on SOC composition, particle phase state and
      viscosity, mixing state, temperature, relative humidity (RH), and reaction time.
      LSOC shows slightly higher potential to deplete chloride than PSOC. Higher
      particle viscosity at low temperatures and RH can hinder these acid displacement
      reactions. Formation of organic salts from these overlooked reactions can alter
      particle physiochemical properties and may affect their reactivity and ability to
      act as cloud condensation and ice nuclei. The release and potential recycling of
      HCl and HNO3 from reacted aerosol particles may have important implications for
      atmospheric chemistry. 

PMID- 25386913
TI  - A stress assembly that confers cell viability by preserving ERES components
      during amino-acid starvation.
AB  - Nutritional restriction leads to protein translation attenuation that results in
      the storage and degradation of free mRNAs in cytoplasmic assemblies. In this
      study, we show in Drosophila S2 cells that amino-acid starvation also leads to
      the inhibition of another major anabolic pathway, the protein transport through
      the secretory pathway, and to the formation of a novel reversible non-membrane
      bound stress assembly, the Sec body that incorporates components of the ER exit
      sites. Sec body formation does not depend on membrane traffic in the early
      secretory pathway, yet requires both Sec23 and Sec24AB. Sec bodies have liquid
      droplet-like properties, and they act as a protective reservoir for ERES
      components to rebuild a functional secretory pathway after re-addition of amino
      acids acting as a part of a survival mechanism. Taken together, we propose that
      the formation of these structures is a novel stress response mechanism to provide
      cell viability during and after nutrient stress.

PMID- 25386914
TI  - Health insurance coverage and its impact on medical cost: observations from the
      floating population in China.
AB  - BACKGROUND: China has the world's largest floating (migrant) population, which
      has characteristics largely different from the rest of the population. Our goal
      is to study health insurance coverage and its impact on medical cost for this
      population. METHODS: A telephone survey was conducted in 2012. 644 subjects were
      surveyed. Univariate and multivariate analysis were conducted on insurance
      coverage and medical cost. RESULTS: 82.2% of the surveyed subjects were covered
      by basic insurance at hometowns with hukou or at residences. Subjects'
      characteristics including age, education, occupation, and presence of chronic
      diseases were associated with insurance coverage. After controlling for
      confounders, insurance coverage was not significantly associated with gross or
      out-of-pocket medical cost. CONCLUSION: For the floating population, health
      insurance coverage needs to be improved. Policy interventions are needed so that
      health insurance can have a more effective protective effect on cost.

PMID- 25386915
TI  - Transition-metal-free direct alkylation of aryl tetrazoles via intermolecular
      oxidative C-N formation.
AB  - A transition-metal-free synthetic approach for constructing alkylated aryl
      tetrazoles has been developed using n-Bu4NI as the catalyst and t-BuOOH as the
      oxidant. It involves the direct C-N bond formation through sp(3) C-H activation.
      A wide range of benzylic C-H substrates (or alkyl ethers) and aryl tetrazoles
      undergo this reaction smoothly to deliver the corresponding products in good
      yields. 

PMID- 25386916
TI  - Advancing drug therapy for brain tumours: a current review of the pro
      inflammatory peptide Substance P and its antagonists as anti-cancer agents.
AB  - Evidence for the involvement of the Substance P (SP)/NK1 receptor system in the
      development and progression of cancer strongly supports its potential as a
      therapeutic target in malignancies. Novel strategies for approaching cancer
      treatment are urgently required particularly with regard to tumours of the
      central nervous system (CNS), which are notoriously difficult to effectively
      treat and associated with extremely poor prognosis for many patients. This is
      due, in part, to the presence of the highly specialised blood-brain barrier,
      which is known to restrict common treatments such as chemotherapy and hinder
      early tumour diagnosis. Additionally, tumours of the CNS are difficult to
      surgically resect completely, often contributing to the resurgence of the disease
      many years later. Interestingly, despite the presence of the blood-brain barrier,
      circulating tumour cells are able to gain entry to the brain and form secondary
      brain tumours; however, the underlying mechanisms of this process remain unclear.
      Tachykinins, in particular Substance P, have been implicated in early blood-brain
      barrier disruption via neurogenic inflammation in a number of other CNS
      pathologies. Recent evidence also suggests that Substance P may play a central
      role in the development of CNS tumours. It has been well established that a
      number of tumour cells express Substance P, NK1 receptors and mRNA for the
      tachykinin NK1 receptor. This increase in the Substance P/NK1 receptor system is
      known to induce proliferation and migration of tumour cells as well as stimulate
      angiogenesis, thus contributing to tumour progression. Accordingly, the NK1
      receptor antagonist presents a novel target for anti-cancer therapy for which a
      number of patents have been filed. This review will examine the role of Substance
      P in the development of CNS tumours and its potential application as an anti
      cancer agent. 

PMID- 25386917
TI  - Possible physiopathological effects of the transglutaminase activity on the
      molecular mechanisms responsible for human neurodegenerative diseases.
AB  - Transglutaminases are a class of 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 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. Recently, transglutaminase activity has
      been shown to be responsible for a widespread human autoimmune disease, the
      Celiac Disease. Interestingly, 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- 25386919
TI  - Connectotyping: model based fingerprinting of the functional connectome.
AB  - A better characterization of how an individual's brain is functionally organized
      will likely bring dramatic advances to many fields of study. Here we show a model
      based approach toward characterizing resting state functional connectivity MRI
      (rs-fcMRI) that is capable of identifying a so-called "connectotype", or
      functional fingerprint in individual participants. The approach rests on a simple
      linear model that proposes the activity of a given brain region can be described
      by the weighted sum of its functional neighboring regions. The resulting
      coefficients correspond to a personalized model-based connectivity matrix that is
      capable of predicting the timeseries of each subject. Importantly, the model
      itself is subject specific and has the ability to predict an individual at a
      later date using a limited number of non-sequential frames. While we show that
      there is a significant amount of shared variance between models across subjects,
      the model's ability to discriminate an individual is driven by unique connections
      in higher order control regions in frontal and parietal cortices. Furthermore, we
      show that the connectotype is present in non-human primates as well, highlighting
      the translational potential of the approach. 

PMID- 25386920
TI  - Study on the traffic air pollution inside and outside a road tunnel in Shanghai,
      China.
AB  - To investigate the vehicle induced air pollution situations both inside and
      outside the tunnel, the field measurement of the pollutants concentrations and
      its diurnal variations was performed inside and outside the Xiangyin tunnel in
      Shanghai from 13:00 on April 24th to 13:00 on April 25th, 2013. The highest
      hourly average concentrations of pollutants were quantified that CO, NO, NO2 and
      NOX inside the tunnel were 13.223 mg/m3, 1.829 mg/m3, 0.291 mg/m3 and 3.029
      mg/m3, respectively, while the lowest ones were 3.086 mg/m3, 0.344 mg/m3, 0.080
      mg/m3 and 0.619 mg/m3. Moreover, the concentrations of pollutants were higher
      during the daytime, and lower at night, which is relevant to the traffic
      conditions inside the tunnel. Pollutants concentrations inside the tunnel were
      much higher than those outside the tunnel. Then in a case of slow wind, the
      effect of wind is much smaller than the impact of pollution sources.
      Additionally, the PM2.5 concentrations climbed to the peak sharply (468.45 ug/m3)
      during the morning rush hours. The concentrations of organic carbon (OC) and
      elemental carbon (EC) in PM2.5 inside the tunnel were 37.09-99.06 ug/m3 and 22.69
      137.99 ug/m3, respectively. Besides, the OC/EC ratio ranged from 0.72 to 2.19
      with an average value of 1.34. Compared with the results of other tunnel
      experiments in Guangzhou and Shenzhen, China, it could be inferred that the
      proportion of HDVs through the Xiangyin tunnel is relatively lower. 

PMID- 25386921
TI  - Tissue distribution, gender- and genotype-dependent expression of autophagy
      related genes in avian species.
AB  - As a result of the genetic selection of broiler (meat-type breeders) chickens for
      enhanced growth rate and lower feed conversion ratio, it has become necessary to
      restrict feed intake. When broilers are fed ad libitum, they would become obese
      and suffer from several health-related problems. A vital adaptation to starvation
      is autophagy, a self-eating mechanism for recycling cellular constituents. The
      autophagy pathway has witnessed dramatic growth in the last few years and
      extensively studied in yeast and mammals however, there is a paucity of
      information in avian (non-mammalian) species. Here we characterized several genes
      involved in autophagosome initiation and elongation in Red Jungle fowl (Gallus
      gallus) and Japanese quail (coturnix coturnix Japonica). Both complexes are
      ubiquitously expressed in chicken and quail tissues (liver, leg and breast
      muscle, brain, gizzard, intestine, heart, lung, kidney, adipose tissue, ovary and
      testis). Alignment analysis showed high similarity (50.7 to 91.5%) between
      chicken autophagy-related genes and their mammalian orthologs. Phylogenetic
      analysis demonstrated that the evolutionary relationship between autophagy genes
      is consistent with the consensus view of vertebrate evolution. Interestingly, the
      expression of autophagy-related genes is tissue- and gender-dependent.
      Furthermore, using two experimental male quail lines divergently selected over 40
      generations for low (resistant, R) or high (sensitive, S) stress response, we
      found that the expression of most studied genes are higher in R compared to S
      line. Together our results indicate that the autophagy pathway is a key molecular
      signature exhibited gender specific differences and likely plays an important
      role in response to stress in avian species.

PMID- 25386922
TI  - PIM kinases as potential therapeutic targets in a subset of peripheral T cell
      lymphoma cases.
AB  - Currently, there is no efficient therapy for patients with peripheral T cell
      lymphoma (PTCL). The Proviral Integration site of Moloney murine leukemia virus
      (PIM) kinases are important mediators of cell survival. We aimed to determine the
      therapeutic value of PIM kinases because they are overexpressed in PTCL patients,
      T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically
      (using small interfering and short hairpin RNAs) and pharmacologically (mainly
      with the pan-PIM inhibitor (PIMi) ETP-39010) in a panel of 8 PTCL cell lines.
      Effects on cell viability, apoptosis, cell cycle, key proteins and gene
      expression were evaluated. Individual inhibition of each of the PIM genes did not
      affect PTCL cell survival, partially because of a compensatory mechanism among
      the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases
      strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in
      part through the induction of DNA damage. Therefore, pan-PIMi synergized with
      Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral
      T cell viability without affecting normal T cells ex vivo. Since anaplastic large
      cell lymphoma (ALK+ ALCL) cell lines were the most sensitive to the pan-PIMi, we
      tested the simultaneous inhibition of ALK and PIM kinases and found a strong
      synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase
      inhibition could be of therapeutic value in a subset of PTCL, especially when
      combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL. 

PMID- 25386924
TI  - Temporal changes in randomness of bird communities across Central Europe.
AB  - Many studies have examined whether communities are structured by random or
      deterministic processes, and both are likely to play a role, but relatively few
      studies have attempted to quantify the degree of randomness in species
      composition. We quantified, for the first time, the degree of randomness in
      forest bird communities based on an analysis of spatial autocorrelation in three
      regions of Germany. The compositional dissimilarity between pairs of forest
      patches was regressed against the distance between them. We then calculated the y
      intercept of the curve, i.e. the 'nugget', which represents the compositional
      dissimilarity at zero spatial distance. We therefore assume, following similar
      work on plant communities, that this represents the degree of randomness in
      species composition. We then analysed how the degree of randomness in community
      composition varied over time and with forest management intensity, which we
      expected to reduce the importance of random processes by increasing the strength
      of environmental drivers. We found that a high portion of the bird community
      composition could be explained by chance (overall mean of 0.63), implying that
      most of the variation in local bird community composition is driven by stochastic
      processes. Forest management intensity did not consistently affect the mean
      degree of randomness in community composition, perhaps because the bird
      communities were relatively insensitive to management intensity. We found a high
      temporal variation in the degree of randomness, which may indicate temporal
      variation in assembly processes and in the importance of key environmental
      drivers. We conclude that the degree of randomness in community composition
      should be considered in bird community studies, and the high values we find may
      indicate that bird community composition is relatively hard to predict at the
      regional scale. 

PMID- 25386923
TI  - The pCri System: a vector collection for recombinant protein expression and
      purification.
AB  - A major bottleneck in structural, biochemical and biophysical studies of proteins
      is the need for large amounts of pure homogenous material, which is generally
      obtained by recombinant overexpression. Here we introduce a vector collection,
      the pCri System, for cytoplasmic and periplasmic/extracellular expression of
      heterologous proteins that allows the simultaneous assessment of prokaryotic and
      eukaryotic host cells (Escherichia coli, Bacillus subtilis, and Pichia pastoris).
      By using a single polymerase chain reaction product, genes of interest can be
      directionally cloned in all vectors within four different rare restriction sites
      at the 5'end and multiple cloning sites at the 3'end. In this way, a number of
      different fusion tags but also signal peptides can be incorporated at the N- and
      C-terminus of proteins, facilitating their expression, solubility and subsequent
      detection and purification. Fusion tags can be efficiently removed by treatment
      with site-specific peptidases, such as tobacco etch virus proteinase, thrombin,
      or sentrin specific peptidase 1, which leave only a few extra residues at the N
      terminus of the protein. The combination of different expression systems in
      concert with the cloning approach in vectors that can fuse various tags makes the
      pCri System a valuable tool for high throughput studies. 

PMID- 25386926
TI  - Species distribution models and impact factor growth in environmental journals:
      methodological fashion or the attraction of global change science.
AB  - In this work, I evaluate the impact of species distribution models (SDMs) on the
      current status of environmental and ecological journals by asking the question to
      which degree development of SDMs in the literature is related to recent changes
      in the impact factors of ecological journals. The hypothesis evaluated states
      that research fronts are likely to attract research attention and potentially
      drive citation patterns, with journals concentrating papers related to the
      research front receiving more attention and benefiting from faster increases in
      their impact on the ecological literature. My results indicate a positive
      relationship between the number of SDM related articles published in a journal
      and its impact factor (IF) growth during the period 2000-09. However, the
      percentage of SDM related papers in a journal was strongly and positively
      associated with the percentage of papers on climate change and statistical
      issues. The results support the hypothesis that global change science has been
      critical in the development of SDMs and that interest in climate change research
      in particular, rather than the usage of SDM per se, appears as an important
      factor behind journal IF increases in ecology and environmental sciences.
      Finally, our results on SDM application in global change science support the view
      that scientific interest rather than methodological fashion appears to be the
      major driver of research attraction in the scientific literature. 

PMID- 25386925
TI  - miR-107 activates ATR/Chk1 pathway and suppress cervical cancer invasion by
      targeting MCL1.
AB  - MicroRNAs (miRNAs) are a class of single-stranded, non-coding RNAs of about 22
      nucleotides in length. Increasing evidence implicates miRNAs may function as
      oncogenes or tumor suppressors. Here we showed that miR-107 directly targeted
      MCL1 and activated ATR/Chk1 pathway to inhibit proliferation, migration and
      invasiveness of cervical cancer cells. Moreover, we found that MCL1 was
      frequently up-regulated in cervical cancer, and knockdown of MCL1 markedly
      inhibited cancer cell proliferation, migration and invasion, whereas ectopic
      expression of MCL1 significantly enhances these properties. The restoration of
      MCL1 expression can counteract the effect of miR-107 on the cancer cells.
      Together, miR-107 is a new regulator of MCL1, and both miR-107 and MCL1 play
      important roles in the pathogenesis of cervical cancer. We have therefore
      identified a mechanism for ATR/Chk1 pathway which involves an increase in miR-107
      leading to a decrease in MCL1. Correspondingly, our results revealed that miR-107
      affected ATR/Chk1 signalling and gene expression, and implicated miR-107 as a
      therapeutic target in human cervical cancer. We also demonstrated that taxol
      attenuated migration and invasion in cervical cancer cells by activating the miR
      107, in which miR-107 play an important role in regulating the expression of
      MCL1. Elucidation of this discovered MCL1 was directly regulated by miR-107 will
      greatly enhance our understanding of the mechanisms responsible for cervical
      cancer and will provide an additional arm for the development of anticancer
      therapies. 

PMID- 25386927
TI  - Epoxidation activities of human cytochromes P450c17 and P450c21.
AB  - Some cytochrome P450 enzymes epoxidize unsaturated substrates, but this activity
      has not been described for the steroid hydroxylases. Physiologic steroid
      substrates, however, lack carbon-carbon double bonds in the parts of the pregnane
      molecules where steroidogenic hydroxylations occur. Limited data on the
      reactivity of steroidogenic P450s toward olefinic substrates exist, and the study
      of occult activities toward alternative substrates is a fundamental aspect of the
      growing field of combinatorial biosynthesis. We reasoned that human P450c17
      (steroid 17-hydroxylase/17,20-lyase, CYP17A1), which 17- and 16alpha-hydroxylates
      progesterone, might catalyze the formation of the 16alpha,17-epoxide from 16,17
      dehydroprogesterone (pregna-4,16-diene-3,20-dione). CYP17A1 catalyzed the novel
      16alpha,17-epoxidation and the ordinarily minor 21-hydroxylation of 16,17
      dehydroprogesterone in a 1:1 ratio. CYP17A1 mutation A105L, which has reduced
      progesterone 16alpha-hydroxylase activity, gave a 1:5 ratio of epoxide:21
      hydroxylated products. In contrast, human P450c21 (steroid 21-hydroxylase,
      CYP21A2) converted 16,17-dehydroprogesterone to the 21-hydroxylated product and
      only a trace of epoxide. CYP21A2 mutation V359A, which has significant 16alpha
      hydroxylase activity, likewise afforded the 21-hydroxylated product and slightly
      more epoxide. CYP17A1 wild-type and mutation A105L do not 21- or 16alpha
      hydroxylate pregnenolone, but the enzymes 21-hydroxylated and 16alpha,17
      epoxidized 16,17-dehydropregnenolone (pregna-5,16-diene-3beta-ol-20-one) in 4:1
      or 12:1 ratios, respectively. Catalase and superoxide dismutase did not prevent
      epoxide formation. The progesterone epoxide was not a time-dependent,
      irreversible CYP17A1 inhibitor. Our substrate modification studies have revealed
      occult epoxidase and 21-hydroxylase activities of CYP17A1, and the fraction of
      epoxide formed correlated with the 16alpha-hydroxylase activity of the enzymes. 

PMID- 25386928
TI  - Survey of surface proteins from the pathogenic Mycoplasma hyopneumoniae strain
      7448 using a biotin cell surface labeling approach.
AB  - The characterization of the repertoire of proteins exposed on the cell surface by
      Mycoplasma hyopneumoniae (M. hyopneumoniae), the etiological agent of enzootic
      pneumonia in pigs, is critical to understand physiological processes associated
      with bacterial infection capacity, survival and pathogenesis. Previous in silico
      studies predicted that about a third of the genes in the M. hyopneumoniae genome
      code for surface proteins, but so far, just a few of them have experimental
      confirmation of their expression and surface localization. In this work, M.
      hyopneumoniae surface proteins were labeled in intact cells with biotin, and
      affinity-captured biotin-labeled proteins were identified by a gel-based liquid
      chromatography-tandem mass spectrometry approach. A total of 20 gel slices were
      separately analyzed by mass spectrometry, resulting in 165 protein
      identifications corresponding to 59 different protein species. The identified
      surface exposed proteins better defined the set of M. hyopneumoniae proteins
      exposed to the host and added confidence to in silico predictions. Several
      proteins potentially related to pathogenesis, were identified, including known
      adhesins and also hypothetical proteins with adhesin-like topologies, consisting
      of a transmembrane helix and a large tail exposed at the cell surface. The
      results provided a better picture of the M. hyopneumoniae cell surface that will
      help in the understanding of processes important for bacterial pathogenesis.
      Considering the experimental demonstration of surface exposure, adhesion-like
      topology predictions and absence of orthologs in the closely related, non
      pathogenic species Mycoplasma flocculare, several proteins could be proposed as
      potential targets for the development of drugs, vaccines and/or immunodiagnostic
      tests for enzootic pneumonia. 

PMID- 25386929
TI  - Metformin in cancer treatment and prevention.
AB  - Patients with diabetes mellitus are at increased risk of cancer development.
      Metformin is a well-established, effective agent for the management of type 2
      diabetes mellitus. Epidemiological studies have identified an association between
      metformin use and a beneficial effect on cancer prevention and treatment, which
      has led to increasing interest in the potential use of metformin as an anticancer
      agent. Basic science has provided a better understanding of the mechanism of
      action of metformin and the potential for metformin to modulate molecular
      pathways involved in cancer cell signaling and metabolism. This article outlines
      the link between metformin and cancer, the potential for metformin in oncology,
      and limitations of currently available evidence. 

PMID- 25386931
TI  - H7N9: preparing for the unexpected in influenza.
AB  - In the years prior to 2013, avian influenza A H7 viruses were a cause of
      significant poultry mortality; however, human illness was generally mild. In
      March 2013, a novel influenza A(H7N9) virus emerged in China as an unexpected
      cause of severe human illness with 36% mortality. Chinese and other public health
      officials responded quickly, characterizing the virus and identifying more than
      400 cases through use of new technologies and surveillance tools made possible by
      past preparedness and response efforts. Genetic sequencing, glycan-array receptor
      binding assays, and ferret studies reveal the H7N9 virus to have increased
      binding to mammalian respiratory cells and to have mutations associated with
      higher virus replication rates and illness severity. New risk-assessment tools
      indicate H7N9 has the potential for further mammalian adaptation with possible
      human-to-human transmission. Vigilant virologic and epidemiologic surveillance is
      needed to monitor H7N9 and detect other unexpected novel influenza viruses that
      may emerge. 

PMID- 25386932
TI  - Pharmacogenetics of cancer drugs.
AB  - The variability in treatment outcomes among patients receiving the same therapy
      for seemingly similar tumors can be attributed in part to genetics. The tumor's
      (somatic) genome largely dictates the effectiveness of the therapy, and the
      patient's (germline) genome influences drug exposure and the patient's
      sensitivity to toxicity. Many potentially clinically useful associations have
      been discovered between common germline genetic polymorphisms and outcomes of
      cancer treatment. This review highlights the germline pharmacogenetic
      associations that are currently being used to guide cancer treatment decisions,
      those that are most likely to someday be clinically useful, and associations that
      are well known but their roles in clinical management are not yet certain. In the
      future, germline genetic information will likely be available from tumor genetic
      analyses, creating an efficient opportunity to integrate the two genomes to
      optimize treatment outcomes for each individual cancer patient. 

PMID- 25386930
TI  - Pathogenesis of macrophage activation syndrome and potential for cytokine-
      directed therapies.
AB  - Macrophage activation syndrome (MAS) is an acute episode of overwhelming
      inflammation characterized by activation and expansion of T lymphocytes and
      hemophagocytic macrophages. In rheumatology, it occurs most frequently in
      patients with systemic juvenile idiopathic arthritis (SJIA) and systemic lupus
      erythematosus. The main clinical manifestations include cytopenias, liver
      dysfunction, coagulopathy resembling disseminated intravascular coagulation, and
      extreme hyperferritinemia. Clinically and pathologically, MAS bears strong
      similarity to hemophagocytic lymphohistiocytosis (HLH), and some authors prefer
      the term secondary HLH to describe it. Central to its pathogenesis is a cytokine
      storm, with markedly increased levels of numerous proinflammatory cytokines
      including IL-1, IL-6, IL-18, TNFalpha, and IFNgamma. Although there is evidence
      that IFNgamma may play a central role in the pathogenesis of MAS, the role of
      other cytokines is still not clear. There are several reports of SJIA-associated
      MAS dramatically benefiting from anakinra, a recombinant IL-1 receptor
      antagonist, but the utility of other biologics in MAS is not clear. The mainstay
      of treatment remains corticosteroids; other medications, including cyclosporine,
      are used in patients who fail to respond. 

PMID- 25386933
TI  - Management of postmenopausal osteoporosis.
AB  - A hallmark of menopause, which follows the decline in the ovarian production of
      estrogen, is the aggressive and persistent loss of bone mineral and structural
      elements leading to loss of bone strength and increased fracture risk. This
      review focuses on newer methods of diagnosing osteoporosis and assessing fracture
      risk, as well as on novel management strategies for prevention and treatment.
      Fracture-risk prediction has been significantly enhanced by the development of
      methods such as the trabecular bone score, which helps assess bone
      microarchitecture and adds value to standard bone densitometry, and the Fracture
      Risk Assessment Tool (FRAX) algorithm techniques. The treatment of osteoporosis,
      which has the goals of fracture prevention and risk reduction, is moving beyond
      traditional monotherapies with antiresorptives and anabolic agents into new
      combination regimens. 

PMID- 25386934
TI  - Neuroblastoma: molecular pathogenesis and therapy.
AB  - Neuroblastoma is a developmental tumor of young children arising from the
      embryonic sympathoadrenal lineage of the neural crest. Neuroblastoma is the
      primary cause of death from pediatric cancer for children between the ages of one
      and five years and accounts for ~13% of all pediatric cancer mortality. Its
      clinical impact and unique biology have made this aggressive malignancy the focus
      of a large concerted translational research effort. New insights into tumor
      biology are driving the development of new classification schemas. Novel targeted
      therapeutic approaches include small-molecule inhibitors as well as epigenetic,
      noncoding-RNA, and cell-based immunologic therapies. In this review, recent
      insights regarding the pathogenesis and biology of neuroblastoma are placed in
      context with the current understanding of tumor biology and tumor/host
      interactions. Systematic classification of patients coupled with therapeutic
      advances point to a future of improved clinical outcomes for this biologically
      distinct and highly aggressive pediatric malignancy. 

PMID- 25386936
TI  - Neoadjuvant therapy for breast cancer.
AB  - Neoadjuvant treatment of breast cancer refers to the use of different treatment
      modalities prior to surgical excision of the tumor. It has been accepted as a
      treatment option for patients with nonmetastatic disease, because it renders
      inoperable tumors operable and increases the rates of breast-conserving surgery,
      while achieving similar long-term clinical outcomes as adjuvant treatment. The
      neoadjuvant setting is being increasingly perceived as a research platform, where
      the biologic effects of traditional anticancer agents can be delineated,
      prognostic and predictive biomarkers can be identified, and the development of
      targeted agents can be expedited. Surrogate endpoints that can predict long-term
      clinical outcome and are evaluable early on, such as the pathologic complete
      response, offer valuable opportunities for rapid assessment of anticancer agents.
      Additionally, efforts for molecular profiling of the post-neoadjuvant residual
      disease hold the potential to lead to personalized therapy for breast cancer
      patients with early-stage high-risk disease. 

PMID- 25386935
TI  - T cell-mediated hypersensitivity reactions to drugs.
AB  - The immunological mechanisms driving delayed hypersensitivity reactions (HSRs) to
      drugs mediated by drug-reactive T lymphocytes are exemplified by several key
      examples and their human leukocyte antigen (HLA) associations: abacavir and HLA
      B*57:01, carbamazepine and HLA-B*15:02, allo-purinol and HLA-B*58:01, and both
      amoxicillin-clavulanate and nevirapine with multiple class I and II alleles. For
      HLA-restricted drug HSRs, specific class I and/or II HLA alleles are necessary
      but not sufficient for tissue specificity and the clinical syndrome. Several
      models have been proposed to explain the immunopathogenesis of severe T cell
      mediated drug HSRs, and our increased understanding of the risk factors and
      mechanisms involved in the development of these reactions will further the
      development of sensitive and specific strategies for preclinical screening that
      will lead to safer and more cost-effective drug design. 

PMID- 25386937
TI  - A new species of Garjainia Ochev, 1958 (Diapsida: Archosauriformes:
      Erythrosuchidae) from the Early Triassic of South Africa.
AB  - A new species of the erythrosuchid archosauriform reptile Garjainia Ochev, 1958
      is described on the basis of disarticulated but abundant and well-preserved
      cranial and postcranial material from the late Early Triassic (late Olenekian)
      Subzone A of the Cynognathus Assemblage Zone of the Burgersdorp Formation
      (Beaufort Group) of the Karoo Basin of South Africa. The new species, G. madiba,
      differs from its unique congener, G. prima from the late Olenekian of European
      Russia, most notably in having large bony bosses on the lateral surfaces of the
      jugals and postorbitals. The new species also has more teeth and a
      proportionately longer postacetabular process of the ilium than G. prima.
      Analysis of G. madiba bone histology reveals thick compact cortices comprised of
      highly vascularized, rapidly forming fibro-lamellar bone tissue, similar to
      Erythrosuchus africanus from Subzone B of the Cynognathus Assemblage Zone. The
      most notable differences between the two taxa are the predominance of a radiating
      vascular network and presence of annuli in the limb bones of G. madiba. These
      features indicate rapid growth rates, consistent with data for many other
      Triassic archosauriforms, but also a high degree of developmental plasticity as
      growth remained flexible. The diagnoses of Garjainia and of Erythrosuchidae are
      addressed and revised. Garjainia madiba is the geologically oldest erythrosuchid
      known from the Southern Hemisphere, and demonstrates that erythrosuchids achieved
      a cosmopolitan biogeographical distribution by the end of the Early Triassic,
      within five million years of the end-Permian mass extinction event. It provides
      new insights into the diversity of the Subzone A vertebrate assemblage, which
      partially fills a major gap between classic 'faunal' assemblages from the older
      Lystrosaurus Assemblage Zone (earliest Triassic) and the younger Subzone B of the
      Cynognathus Assemblage Zone (early Middle Triassic). 

PMID- 25386939
TI  - Distinct microRNA expression profiles in mouse renal cortical tissue after 177Lu
      octreotate administration.
AB  - AIM: The aim of this study was to investigate the variation of the miRNA
      expression levels in normal renal cortical tissue after 177Lu-octreotate
      administration, a radiopharmaceutical used for treatment of neuroendocrine
      cancers. METHODS: Female BALB/c nude mice were i.v. injected with 1.3, 3.6, 14,
      45, or 140 MBq 177Lu-octreotate, while control animals received saline. The
      animals were killed at 24 h after injection and total RNA, including miRNA, was
      extracted from the renal cortical tissue and hybridized to the Mouse miRNA Oligo
      chip 4plex to identify differentially regulated miRNAs between exposed and
      control samples. RESULTS: In total, 57 specific miRNAs were differentially
      regulated in the exposed renal cortical tissues with 1, 29, 21, 27, and 31 miRNAs
      identified per dose-level (0.13, 0.34, 1.3, 4.3, and 13 Gy, respectively). No
      miRNAs were commonly regulated at all dose levels. miR-194, miR-107, miR-3090,
      and miR-3077 were commonly regulated at 0.34, 1.3, 4.3, and 13 Gy. Strong effects
      on cellular mechanisms ranging from immune response to p53 signaling and cancer
      related pathways were observed at the highest absorbed dose. Thirty-nine of the
      57 differentially regulated miRNAs identified in the present study have
      previously been associated with response to ionizing radiation, indicating common
      radiation responsive pathways. CONCLUSION: In conclusion, the 177Lu-octreotate
      associated miRNA signatures were generally dose-specific, thereby illustrating
      transcriptional regulation of radiation responsive miRNAs. Taken together, these
      results imply the importance of miRNAs in early immunological responses in the
      kidneys following 177Lu-octreotate administration.

PMID- 25386940
TI  - Environmental drivers of Culicoides phenology: how important is species-specific
      variation when determining disease policy?
AB  - Since 2006, arboviruses transmitted by Culicoides biting midges (Diptera:
      Ceratopogonidae) have caused significant disruption to ruminant production in
      northern Europe. The most serious incursions involved strains of bluetongue virus
      (BTV), which cause bluetongue (BT) disease. To control spread of BTV, movement of
      susceptible livestock is restricted with economic and animal welfare impacts. The
      timing of BTV transmission in temperate regions is partly determined by the
      seasonal presence of adult Culicoides females. Legislative measures therefore
      allow for the relaxation of ruminant movement restrictions during winter, when
      nightly light-suction trap catches of Culicoides fall below a threshold (the
      'seasonally vector free period': SVFP). We analysed five years of time-series
      surveillance data from light-suction trapping in the UK to investigate whether
      significant inter-specific and yearly variation in adult phenology exists, and
      whether the SVFP is predictable from environmental factors. Because female vector
      Culicoides are not easily morphologically separated, inter-specific comparisons
      in phenology were drawn from male populations. We demonstrate significant inter
      specific differences in Culicoides adult phenology with the season of Culicoides
      scoticus approximately eight weeks shorter than Culicoides obsoletus. Species
      specific differences in the length of the SVFP were related to host density and
      local variation in landscape habitat. When the Avaritia Culicoides females were
      modelled as a group (as utilised in the SFVP), we were unable to detect links
      between environmental drivers and phenological metrics. We conclude that the
      current treatment of Avaritia Culicoides as a single group inhibits understanding
      of environmentally-driven spatial variation in species phenology and hinders the
      development of models for predicting the SVFP from environmental factors.
      Culicoides surveillance methods should be adapted to focus on concentrated
      assessments of species-specific abundance during the start and end of seasonal
      activity in temperate regions to facilitate refinement of ruminant movement
      restrictions thereby reducing the impact of Culicoides-borne arboviruses. 

PMID- 25386941
TI  - Gut microbiome in Down syndrome.
AB  - BACKGROUND: Premature aging seriously compromises the health status of Down
      Syndrome (DS) persons. Since human aging has been associated with a deterioration
      of the gut microbiota (GM)-host mutualism, here we investigated the composition
      of GM in DS. METHODS: The observational study presented involved 17 adult DS
      persons. We characterized the GM structure by 454 pyrosequencing of the V4 region
      of the 16S rRNA gene. DS microbiome was compared with that of age-matched healthy
      non-trisomic adults enrolled in the same geographic area. RESULTS AND
      CONCLUSIONS: The dominant GM fraction of DS persons showed an overall mutualistic
      immune-modulatory layout, comparable to that of healthy controls. This makes GM a
      possible factor counteracting the genetic determined acceleration of immune
      senescence in DS persons. However, we also found detectable signatures specific
      for DS among subdominant GM components, such as the increase of
      Parasporobacterium and Sutterella. In particular, the abundance of this last
      microorganism significantly correlated with the Aberrant Behavior Checklist (ABC)
      total score, allowing us to hypothesize a possible role for this microbial genus
      in behavioral features in DS.

PMID- 25386942
TI  - PSMA ligand conjugated PCL-PEG polymeric micelles targeted to prostate cancer
      cells.
AB  - In this content, a small molecular ligand of prostate specific membrane antigen
      (SMLP) conjugated poly (caprolactone) (PCL)-b-poly (ethylene glycol) (PEG)
      copolymers with different block lengths were synthesized to construct a
      satisfactory drug delivery system. Four different docetaxel-loaded polymeric
      micelles (DTX-PMs) were prepared by dialysis with particle sizes less than 60 nm
      as characterized by dynamic light scattering (DLS) and transmission electron
      microscope (TEM). Optimization of the prepared micelles was conducted based on
      short-term stability and drug-loading content. The results showed that optimized
      systems were able to remain stable over 7 days. Compared with Taxotere, DTX-PMs
      with the same ratio of hydrophilic/hydrophobic chain length displayed similar
      sustained release behaviors. The cytotoxicity of the optimized targeted DTX
      PCL12K-PEG5K-SMLP micelles (DTX-PMs2) and non-targeted DTX-PCL12K-mPEG5K micelles
      (DTX-PMs1) were evaluated by MTT assays using prostate specific membrane antigen
      (PSMA) positive prostate adenocarcinoma cells (LNCaP). The results showed that
      the targeted micelles had a much lower IC50 than their non-targeted counterparts
      (48 h: 0.87 +/- 0.27 vs 13.48 +/- 1.03 ug/ml; 72 h: 0.02 +/- 0.008 vs 1.35 +/-
      0.54 ug/ml). In vitro cellular uptake of PMs2 showed 5-fold higher fluorescence
      intensity than that of PMs1 after 4 h incubation. According to these results, the
      novel nano-sized drug delivery system based on DTX-PCL-PEG-SMLP offers great
      promise for the treatment of prostatic cancer.

PMID- 25386943
TI  - Australian gay and bisexual men's attitudes to HIV treatment as prevention in
      repeated, national surveys, 2011-2013.
AB  - OBJECTIVE: Assess the acceptability of HIV treatment as prevention and early
      antiretroviral treatment among gay and bisexual men in Australia and any changes
      in attitudes over time. METHODS: National, online, cross-sectional surveys of gay
      and bisexual men were repeated in 2011 and 2013. Changes in attitudes to HIV
      treatment over time were assessed with multivariate analysis of variance. The
      characteristics of men who agreed that HIV treatment prevented transmission and
      thought that early treatment was necessary were identified with multivariate
      logistic regression. RESULTS: In total, 2599 HIV-negative, untested and HIV
      positive men participated (n = 1283 in 2011 and n = 1316 in 2013). Attitudes
      changed little between 2011 and 2013; most participants remained sceptical about
      the preventative benefits of HIV treatment. In 2013, only 2.6% of men agreed that
      HIV treatment prevented transmission; agreement was associated with being HIV
      positive, having an HIV-positive regular partner, and having received HIV post
      exposure prophylaxis. In contrast, 71.8% agreed that early antiretroviral
      treatment is necessary; younger men were more likely and HIV-positive men and
      participants with HIV-positive partners were much less likely to agree with this.
      CONCLUSIONS: Promoting the individual health benefits of HIV treatment rather
      than its preventative benefits remains more acceptable to Australian gay and
      bisexual men.

PMID- 25386944
TI  - The omega subunit of RNA polymerase is essential for thermal acclimation of the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - The rpoZ gene encodes the small omega subunit of RNA polymerase. A DeltarpoZ
      strain of the cyanobacterium Synechocystis sp. PCC 6803 grew well in standard
      conditions (constant illumination at 40 umol photons m(-2) s(-1); 32 degrees C;
      ambient CO2) but was heat sensitive and died at 40 degrees C. In the control
      strain, 71 genes were at least two-fold up-regulated and 91 genes down-regulated
      after a 24-h treatment at 40 degrees C, while in DeltarpoZ 394 genes responded to
      heat. Only 62 of these heat-responsive genes were similarly regulated in both
      strains, and 80% of heat-responsive genes were unique for DeltarpoZ. The RNA
      polymerase core and the primary sigma factor SigA were down-regulated in the
      control strain at 40 degrees C but not in DeltarpoZ. In accordance with reduced
      RNA polymerase content, the total RNA content of mild-heat-stress-treated cells
      was lower in the control strain than in DeltarpoZ. Light-saturated photosynthetic
      activity decreased more in DeltarpoZ than in the control strain upon mild heat
      stress. The amounts of photosystem II and rubisco decreased at 40 degrees C in
      both strains while PSI and the phycobilisome antenna protein allophycocyanin
      remained at the same level as in standard conditions. The phycobilisome rod
      proteins, phycocyanins, diminished during the heat treatment in DeltarpoZ but not
      in the control strain, and the nblA1 and nblA2 genes (encode NblA proteins
      required for phycobilisome degradation) were up-regulated only in DeltarpoZ. Our
      results show that the omega subunit of RNAP is essential in heat stress because
      it is required for heat acclimation of diverse cellular processes.

PMID- 25386945
TI  - A transdiagnostic community-based mental health treatment for comorbid disorders:
      development and outcomes of a randomized controlled trial among Burmese refugees
      in Thailand.
AB  - BACKGROUND: Existing studies of mental health interventions in low-resource
      settings have employed highly structured interventions delivered by non
      professionals that typically do not vary by client. Given high comorbidity among
      mental health problems and implementation challenges with scaling up multiple
      structured evidence-based treatments (EBTs), a transdiagnostic treatment could
      provide an additional option for approaching community-based treatment of mental
      health problems. Our objective was to test such an approach specifically designed
      for flexible treatments of varying and comorbid disorders among trauma survivors
      in a low-resource setting. METHODS AND FINDINGS: We conducted a single-blinded,
      wait-list randomized controlled trial of a newly developed transdiagnostic
      psychotherapy, Common Elements Treatment Approach (CETA), for low-resource
      settings, compared with wait-list control (WLC). CETA was delivered by lay
      workers to Burmese survivors of imprisonment, torture, and related traumas, with
      flexibility based on client presentation. Eligible participants reported trauma
      exposure and met severity criteria for depression and/or posttraumatic stress
      (PTS). Participants were randomly assigned to CETA (n = 182) or WLC (n = 165).
      Outcomes were assessed by interviewers blinded to participant allocation using
      locally adapted standard measures of depression and PTS (primary outcomes) and
      functional impairment, anxiety symptoms, aggression, and alcohol use (secondary
      outcomes). Primary analysis was intent-to-treat (n = 347), including 73
      participants lost to follow-up. CETA participants experienced significantly
      greater reductions of baseline symptoms across all outcomes with the exception of
      alcohol use (alcohol use analysis was confined to problem drinkers). The
      difference in mean change from pre-intervention to post-intervention between
      intervention and control groups was -0.49 (95% CI: -0.59, -0.40) for depression, 
      0.43 (95% CI: -0.51, -0.35) for PTS, -0.42 (95% CI: -0.58, -0.27) for functional
      impairment, -0.48 (95% CI: -0.61, -0.34) for anxiety, -0.24 (95% CI: -0.34, 
      0.15) for aggression, and -0.03 (95% CI: -0.44, 0.50) for alcohol use. This
      corresponds to a 77% reduction in mean baseline depression score among CETA
      participants compared to a 40% reduction among controls, with respective values
      for the other outcomes of 76% and 41% for anxiety, 75% and 37% for PTS, 67% and
      22% for functional impairment, and 71% and 32% for aggression. Effect sizes
      (Cohen's d) were large for depression (d = 1.16) and PTS (d = 1.19); moderate for
      impaired function (d = 0.63), anxiety (d = 0.79), and aggression (d = 0.58); and
      none for alcohol use. There were no adverse events. Limitations of the study
      include the lack of long-term follow-up, non-blinding of service providers and
      participants, and no placebo or active comparison intervention. CONCLUSIONS: CETA
      provided by lay counselors was highly effective across disorders among trauma
      survivors compared to WLCs. These results support the further development and
      testing of transdiagnostic approaches as possible treatment options alongside
      existing EBTs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01459068 Please see
      later in the article for the Editors' Summary.

PMID- 25386947
TI  - Divergent evolution of the activity and regulation of the glutamate decarboxylase
      systems in Listeria monocytogenes EGD-e and 10403S: roles in virulence and acid
      tolerance.
AB  - The glutamate decarboxylase (GAD) system has been shown to be important for the
      survival of Listeria monocytogenes in low pH environments. The bacterium can use
      this faculty to maintain pH homeostasis under acidic conditions. The accepted
      model for the GAD system proposes that the antiport of glutamate into the
      bacterial cell in exchange for gamma-aminobutyric acid (GABA) is coupled to an
      intracellular decarboxylation reaction of glutamate into GABA that consumes
      protons and therefore facilitates pH homeostasis. Most strains of L.
      monocytogenes possess three decarboxylase genes (gadD1, D2 & D3) and two
      antiporter genes (gadT1 & gadT2). Here, we confirm that the gadD3 encodes a
      glutamate decarboxylase dedicated to the intracellular GAD system (GADi), which
      produces GABA from cytoplasmic glutamate in the absence of antiport activity. We
      also compare the functionality of the GAD system between two commonly studied
      reference strains, EGD-e and 10403S with differences in terms of acid resistance.
      Through functional genomics we show that EGD-e is unable to export GABA and
      relies exclusively in the GADi system, which is driven primarily by GadD3 in this
      strain. In contrast 10403S relies upon GadD2 to maintain both an intracellular
      and extracellular GAD system (GADi/GADe). Through experiments with a murinised
      variant of EGD-e (EGDm) in mice, we found that the GAD system plays a significant
      role in the overall virulence of this strain. Double mutants lacking either
      gadD1D3 or gadD2D3 of the GAD system displayed reduced acid tolerance and were
      significantly affected in their ability to cause infection following oral
      inoculation. Since EGDm exploits GADi but not GADe the results indicate that the
      GADi system makes a contribution to virulence within the mouse. Furthermore, we
      also provide evidence that there might be a separate line of evolution in the GAD
      system between two commonly used reference strains. 

PMID- 25386946
TI  - Smart Soup, a traditional Chinese medicine formula, ameliorates amyloid pathology
      and related cognitive deficits.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes
      substantial public health care burdens. Intensive efforts have been made to find
      effective and safe disease-modifying treatment and symptomatic intervention
      alternatives against AD. Smart Soup (SS), a Chinese medicine formula composed of
      Rhizoma Acori Tatarinowii (AT), Poria cum Radix Pini (PRP) and Radix Polygalae
      (RP), is a typical prescription against memory deficits. Here, we assessed the
      efficacy of SS against AD. Oral administration of SS ameliorated the cognitive
      impairment of AD transgenic mice, with reduced Abeta levels, retarded Abeta
      amyloidosis and reduced Abeta-induced gliosis and neuronal loss in the brains of
      AD mice. Consistently, SS treatment reduced amyloid-related locomotor
      dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies
      showed that RP reduced Abeta generation, whereas AT and PRP exerted
      neuroprotective effects against Abeta. Taken together, our study indicates that
      SS could be effective against AD, providing a practical therapeutic strategy
      against the disease. 

PMID- 25386948
TI  - Streptococcus mitis induces conversion of Helicobacter pylori to coccoid cells
      during co-culture in vitro.
AB  - Helicobacter pylori (H. pylori) is a major gastric pathogen that has been
      associated with humans for more than 60,000 years. H. pylori causes different
      gastric diseases including dyspepsia, ulcers and gastric cancers. Disease
      development depends on several factors including the infecting H. pylori strain,
      environmental and host factors. Another factor that might influence H. pylori
      colonization and diseases is the gastric microbiota that was overlooked for long
      because of the belief that human stomach was a hostile environment that cannot
      support microbial life. Once established, H. pylori mainly resides in the gastric
      mucosa and interacts with the resident bacteria. How these interactions impact on
      H. pylori-caused diseases has been poorly studied in human. In this study, we
      analyzed the interactions between H. pylori and two bacteria, Streptococcus mitis
      and Lactobacillus fermentum that are present in the stomach of both healthy and
      gastric disease human patients. We have found that S. mitis produced and released
      one or more diffusible factors that induce growth inhibition and coccoid
      conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum
      secreted factors that promote survival of S. mitis during the stationary phase of
      growth. Using a metabolomics approach, we identified compounds that might be
      responsible for the conversion of H. pylori from spiral to coccoid cells. This
      study provide evidences that gastric bacteria influences H. pylori physiology and
      therefore possibly the diseases this bacterium causes.

PMID- 25386949
TI  - Ginsenoside Rb1 prevents H2O2-induced HUVEC senescence by stimulating sirtuin-1
      pathway.
AB  - PURPOSES: We have previously reported that Ginsenoside Rb1 may effectively
      prevent HUVECs from senescence, however, the detailed mechanism has not
      demonstrated up to now. Recent studies have shown that sirtuin-1 (Sirt1) plays an
      important role in the development of endothelial senescence. The purpose of this
      study was to explore whether Sirt1 is involved in the action of Ginsenoside Rb1
      regarding protection against H2O2-induced HUVEC Senescence. METHODS AND RESULTS:
      Senescence induced by hydrogen peroxide (H2O2) in human umbilical vein
      endothelial cells (HUVECs) was examined by analyzing plasminogen activator
      inhibitor-1 (PAI-1) expression, cell morphology, and senescence-associated beta
      galactosidase (SA-beta-gal) activity. The results revealed that 42% of control
      treated HUVECs were SA-beta-gal positive after treatment by 60 umol/L H2O2,
      however, this particular effect of H2O2 was decreased more than 2-fold (19%) in
      the HUVECs when pretreated with Rb1 (20 umol/L) for 30 min. Additionally, Rb1
      decreased eNOS acetylation, as well as promoted more NO production that was
      accompanied by an increase in Sirt1 expression. Furthermore, upon knocking down
      Sirt1, the effect of Rb1 on HUVEC senescence was blunted. CONCLUSIONS: The
      present study indicated that Ginsenoside Rb1 acts through stimulating Sirt1 in
      order to protect against endothelial senescence and dysfunction. As such, Sirt1
      appears to be of particular importance in maintaining endothelial functions and
      delaying vascular aging.

PMID- 25386951
TI  - Evaluation of Sports Nutrition Knowledge and Recommendations Among High School
      Coaches.
AB  - The objectives of this study were to evaluate high school coaches' knowledge in
      sports nutrition and the nutritional practices they recommend to their athletes.
      Forty-seven high school coaches in "leanness" and "non-leanness" sports from the
      greater region of Quebec (women = 44.7%) completed a questionnaire on nutritional
      knowledge and practices. "Leanness sports" were defined as sports where leanness
      or/and low bodyweight were considered important (e.g., cheerleading, swimming and
      gymnastics), and "non-leanness sports" were defined as sports where these factors
      are less important (e.g., football). Participants obtained a total mean score of
      68.4% for the nutrition knowledge part of the questionnaire. More specifically,
      less than 30% of the coaches could answer correctly some general nutrition
      questions regarding carbohydrates and lipids. No significant difference in
      nutrition knowledge was observed between coaches from "leanness" and "non
      leanness" sports or between men and women. Respondents with a university
      education scored higher than the others (73.3% vs. 63.3%, p < .05). Coaches who
      participated in coaching certification also obtained better results than those
      without a coaching certification. The most popular source of information about
      nutrition used by coaches was the Internet at 55%. The two most popular nutrition
      practices that coaches recommended to improve athlete performance were hydration
      and consumption of protein-rich foods. Recommendation for nutritional supplements
      use was extremely rare and was suggested only by football coaches, a nonleanness
      sport. Findings from this study indicate that coaches need sports nutrition
      education and specific training. 

PMID- 25386950
TI  - The kSORT assay to detect renal transplant patients at high risk for acute
      rejection: results of the multicenter AART study.
AB  - BACKGROUND: Development of noninvasive molecular assays to improve disease
      diagnosis and patient monitoring is a critical need. In renal transplantation,
      acute rejection (AR) increases the risk for chronic graft injury and failure.
      Noninvasive diagnostic assays to improve current late and nonspecific diagnosis
      of rejection are needed. We sought to develop a test using a simple blood gene
      expression assay to detect patients at high risk for AR. METHODS AND FINDINGS: We
      developed a novel correlation-based algorithm by step-wise analysis of gene
      expression data in 558 blood samples from 436 renal transplant patients collected
      across eight transplant centers in the US, Mexico, and Spain between 5 February
      2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal
      Transplantation (AART) study. Gene expression was assessed by quantitative real
      time PCR (QPCR) in one center. A 17-gene set--the Kidney Solid Organ Response
      Test (kSORT)--was selected in 143 samples for AR classification using
      discriminant analysis (area under the receiver operating characteristic curve
      [AUC] = 0.94; 95% CI 0.91-0.98), validated in 124 independent samples (AUC =
      0.95; 95% CI 0.88-1.0) and evaluated for AR prediction in 191 serial samples,
      where it predicted AR up to 3 mo prior to detection by the current gold standard
      (biopsy). A novel reference-based algorithm (using 13 12-gene models) was
      developed in 100 independent samples to provide a numerical AR risk score, to
      classify patients as high risk versus low risk for AR. kSORT was able to detect
      AR in blood independent of age, time post-transplantation, and sample source
      without additional data normalization; AUC = 0.93 (95% CI 0.86-0.99). Further
      validation of kSORT is planned in prospective clinical observational and
      interventional trials. CONCLUSIONS: The kSORT blood QPCR assay is a noninvasive
      tool to detect high risk of AR of renal transplants. Please see later in the
      article for the Editors' Summary.

PMID- 25386952
TI  - Short communication: Longitudinal changes in peripheral blood NK cells during the
      first year of HIV-1 Infection in CD4Low and CD4High patient groups.
AB  - Natural killer (NK) cells may modulate the pathogenesis of primary HIV-1
      infection. However, the relationship between the number and function of NK cells
      during an acute HIV-1 infection and HIV-1 disease progression remains to be
      elucidated. In this study, we enrolled two distinct patient groups. One group
      progressed to where their CD4 cell counts fell below 200 cells/MUl within 2 years
      (CD4Low group), while the CD4 cell counts of the other group remained above 500
      cells/MUl for over 2 years (CD4High group). We compared the number and function
      of NK cells during the first year of HIV-1 infection between the two distinct
      groups. We found that the number of total NK cells and the number of cells in the
      CD56(dim)CD16(pos) subset rapidly decreased in both groups during early HIV-1
      infection. The absolute number of total NK cells and CD56(dim)CD16(pos) NK cells
      was significantly higher in the CD4High group when compared to the CD4Low group
      during the first month of infection. No significant difference between the
      numbers of CD56(bright)CD16(neg) NK cells of the two groups was observed.
      However, more CD56(neg)CD16(pos) NK cells were found in the CD4Low group than in
      the CD4High group. We also found that NK cell function increased within the first
      3 months of HIV-1 infection in the CD4High group and then exhibited a decreasing
      trend. However, in the CD4Low group, NK cell function did not increase
      significantly within the first 3 months of HIV-1 infection but then gradually
      increased. We concluded, therefore, that robust NK functioning cells that are
      present during an acute HIV-1 infection might be beneficial in controlling HIV-1
      disease progression.

PMID- 25386953
TI  - Modeling spatial and temporal variability of residential air exchange rates for
      the Near-Road Exposures and Effects of Urban Air Pollutants Study (NEXUS).
AB  - Air pollution health studies often use outdoor concentrations as exposure
      surrogates. Failure to account for variability of residential infiltration of
      outdoor pollutants can induce exposure errors and lead to bias and incorrect
      confidence intervals in health effect estimates. The residential air exchange
      rate (AER), which is the rate of exchange of indoor air with outdoor air, is an
      important determinant for house-to-house (spatial) and temporal variations of air
      pollution infiltration. Our goal was to evaluate and apply mechanistic models to
      predict AERs for 213 homes in the Near-Road Exposures and Effects of Urban Air
      Pollutants Study (NEXUS), a cohort study of traffic-related air pollution
      exposures and respiratory effects in asthmatic children living near major roads
      in Detroit, Michigan. We used a previously developed model (LBL), which predicts
      AER from meteorology and questionnaire data on building characteristics related
      to air leakage, and an extended version of this model (LBLX) that includes
      natural ventilation from open windows. As a critical and novel aspect of our AER
      modeling approach, we performed a cross validation, which included both parameter
      estimation (i.e., model calibration) and model evaluation, based on daily AER
      measurements from a subset of 24 study homes on five consecutive days during two
      seasons. The measured AER varied between 0.09 and 3.48 h(-1) with a median of
      0.64 h(-1). For the individual model-predicted and measured AER, the median
      absolute difference was 29% (0.19 h-1) for both the LBL and LBLX models. The LBL
      and LBLX models predicted 59% and 61% of the variance in the AER, respectively.
      Daily AER predictions for all 213 homes during the three year study (2010-2012)
      showed considerable house-to-house variations from building leakage differences,
      and temporal variations from outdoor temperature and wind speed fluctuations.
      Using this novel approach, NEXUS will be one of the first epidemiology studies to
      apply calibrated and home-specific AER models, and to include the spatial and
      temporal variations of AER for over 200 individual homes across multiple years
      into an exposure assessment in support of improving risk estimates.

PMID- 25386954
TI  - Spatial analysis of the distribution, risk factors and access to medical
      resources of patients with hepatitis B in Shenzhen, China.
AB  - Considering the high morbidity of hepatitis B in China, many epidemiological
      studies based on classic medical statistical analysis have been started but lack
      spatial information. However, spatial information such as the spatial
      distribution, autocorrelation and risk factors of the disease is of great help in
      studying patients with hepatitis B. This study examined 2851 cases of hepatitis B
      that were hospitalized in Shenzhen in 2010 and studied the spatial distribution,
      risk factors and spatial access to health services using spatial interpolation,
      Pearson correlation analysis and the improved two-step floating catchment area
      method. The results showed that the spatial distribution of hepatitis B, along
      with risk factors as well as spatial access to the regional medical resources,
      was uneven and mainly concentrated in the south and southwest of Shenzhen in
      2010. In addition, the distribution characteristics of hepatitis B revealed a
      positive correlation between four types of service establishments and risk
      factors for the disease. The Pearson correlation coefficients are 0.566, 0.515,
      0.626, 0.538 corresponding to bath centres, beauty salons, massage parlours and
      pedicure parlours (p < 0.05). Additionally, the allocation of medical resources
      for hepatitis B is adequate, as most patients could be treated at nearby
      hospitals.

PMID- 25386955
TI  - Evaluation of mobility, bioavailability and toxicity of Pb and Cd in contaminated
      soil using TCLP, BCR and earthworms.
AB  - The objective of the present study was to investigate the reduction of mobility,
      availability and toxicity found in soil contaminated with lead (Pb) and cadmium
      (Cd) from Santo Amaro Municipality, Bahia, Brazil using two combined methods,
      commonly tested separately according to the literature: metal mobilization with
      phosphates and phytoextraction. The strategy applied was the treatment with two
      sources of phosphates (separately and mixed) followed by phytoremediation with
      vetiver grass (Vetiveria zizanioides (L.)). The treatments applied (in
      triplicates) were: T1-potassium dihydrogen phosphate (KH2PO4); T2-reactive
      natural phosphate fertilizer (NRP) and; T3-a mixture 1:1 of KH2PO4 and NRP. After
      this step, untreated and treated soils were planted with vetiver grass. The
      extraction procedures and assays applied to contaminated soil before and after
      the treatments included metal mobility test (TCLP); sequential extraction with
      BCR method; toxicity assays with Eisenia andrei. The soil-to-plant transfer
      factors (TF) for Pb and Cd were estimated in all cases. All treatments with
      phosphates followed by phytoremediation reduced the mobility and availability of
      Pb and Cd, being KH2PO4 (T1) plus phytoremediation the most effective one. Soil
      toxicity however, remained high after all treatments.

PMID- 25386956
TI  - The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism
      spectrum disorders.
AB  - Elevated whole-blood serotonin and decreased plasma melatonin (a circadian
      synchronizer hormone that derives from serotonin) have been reported
      independently in patients with autism spectrum disorders (ASDs). Here, we
      explored, in parallel, serotonin, melatonin and the intermediate N
      acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives.
      We then investigated the clinical correlates of these biochemical parameters.
      Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278
      patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199
      mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the
      previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well
      as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th
      percentile of the control group, respectively. In addition, this study reveals an
      increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption
      of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also
      observed in the first-degree relatives of patients. A score combining impairments
      of serotonin, NAS and melatonin distinguished between patients and controls with
      a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit
      was only significantly associated with insomnia. Impairments of melatonin
      synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are
      highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very
      frequent trait in patients and may represent a useful biomarker for a large
      subgroup of individuals with ASD. 

PMID- 25386957
TI  - Long-term exposure to intranasal oxytocin in a mouse autism model.
AB  - Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is
      currently in clinical trials for the treatment of autism spectrum disorder (ASD).
      Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown
      that there may be detrimental effects of long-term intranasal administration,
      raising the questions about safety and efficacy. To investigate the effects of OT
      on the aspects of ASD phenotype, we conducted the first study of chronic
      intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J
      inbred strain (BTBR), which displays low sociability and high repetitive
      behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8  IU/kg of OT
      intranasally, daily for 30 days, starting on day 21. We ran a well-characterized
      set of behavioral tasks relevant to diagnostic and associated symptoms of autism,
      including juvenile reciprocal social interactions, three-chambered social
      approach, open-field exploratory activity, repetitive self-grooming and fear
      conditioned learning and memory, some during and some post treatment. Intranasal
      OT did not improve autism-relevant behaviors in BTBR, except for female sniffing
      in the three-chambered social interaction test. Male saline-treated BTBR mice
      showed increased interest in a novel mouse, both in chamber time and sniffing
      time, whereas OT-treated male BTBR mice showed a preference for the novel mouse
      in sniffing time only. No deleterious effects of OT were detected in either B6 or
      BTBR mice, except possibly for the lack of a preference for the novel mouse's
      chamber in OT-treated male BTBR mice. These results highlight the complexity
      inherent in understanding the effects of OT on behavior. Future investigations of
      chronic intranasal OT should include a wider dose range and early developmental
      time points in both healthy rodents and ASD models to affirm the efficacy and
      safety of OT. 

PMID- 25386958
TI  - Time-dependent metabolomic profiling of Ketamine drug action reveals hippocampal
      pathway alterations and biomarker candidates.
AB  - Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has fast-acting
      antidepressant activities and is used for major depressive disorder (MDD)
      patients who show treatment resistance towards drugs of the selective serotonin
      reuptake inhibitor (SSRI) type. In order to better understand Ketamine's mode of
      action, a prerequisite for improved drug development efforts, a detailed
      understanding of the molecular events elicited by the drug is mandatory. In the
      present study we have carried out a time-dependent hippocampal metabolite
      profiling analysis of mice treated with Ketamine. After a single injection of
      Ketamine, our metabolomics data indicate time-dependent metabolite level
      alterations starting already after 2 h reflecting the fast antidepressant effect
      of the drug. In silico pathway analyses revealed that several hippocampal
      pathways including glycolysis/gluconeogenesis, pentose phosphate pathway and
      citrate cycle are affected, apparent by changes not only in metabolite levels but
      also connected metabolite level ratios. The results show that a single injection
      of Ketamine has an impact on the major energy metabolism pathways. Furthermore,
      seven of the identified metabolites qualify as biomarkers for the Ketamine drug
      response. 

PMID- 25386959
TI  - Codeine-induced hyperalgesia and allodynia: investigating the role of glial
      activation.
AB  - Chronic morphine therapy has been associated with paradoxically increased pain.
      Codeine is a widely used opioid, which is metabolized to morphine to elicit
      analgesia. Prolonged morphine exposure exacerbates pain by activating the innate
      immune toll-like receptor-4 (TLR4) in the central nervous system. In silico
      docking simulations indicate codeine also docks to MD2, an accessory protein for
      TLR4, suggesting potential to induce TLR4-dependent pain facilitation. We
      hypothesized codeine would cause TLR4-dependent hyperalgesia/allodynia that is
      disparate from its opioid receptor-dependent analgesic rank potency. Hyperalgesia
      and allodynia were assessed using hotplate and von Frey tests at days 0, 3 and 5
      in mice receiving intraperitoneal equimolar codeine (21 mg kg(-1)), morphine (20
      mg kg(-1)) or saline, twice daily. This experiment was repeated in animals with
      prior partial nerve injury and in TLR4 null mutant mice. Interventions with
      interleukin-1 receptor antagonist (IL-1RA) and glial-attenuating drug ibudilast
      were assessed. Analyses of glial activation markers (glial fibrillary acid
      protein and CD11b) in neuronal tissue were conducted at the completion of
      behavioural testing. Despite providing less acute analgesia (P=0.006), codeine
      induced similar hotplate hyperalgesia to equimolar morphine vs saline (-9.5 s,
      P<0.01 and -7.3 s, P<0.01, respectively), suggesting codeine does not rely upon
      conversion to morphine to increase pain sensitivity. This highlights the
      potential non-opioid receptor-dependent nature of codeine-enhanced pain
      sensitivity-although the involvement of other codeine metabolites cannot be ruled
      out. IL-1RA reversed codeine-induced hyperalgesia (P<0.001) and allodynia
      (P<0.001), and TLR4 knock-out protected against codeine-induced changes in pain
      sensitivity. Glial attenuation with ibudilast reversed codeine-induced allodynia
      (P<0.001), and thus could be investigated further as potential treatment for
      codeine-induced pain enhancement. 

PMID- 25386960
TI  - p, p'-Dichlorodiphenyldichloroethylene induces colorectal adenocarcinoma cell
      proliferation through oxidative stress.
AB  - p, p'-Dichlorodiphenyldichloroethylene (DDE), the major metabolite of
      Dichlorodiphenyltrichloroethane (DDT), is an organochlorine pollutant and
      associated with cancer progression. The present study investigated the possible
      effects of p,p'-DDE on colorectal cancer and the involved molecular mechanism.
      The results indicated that exposure to low concentrations of p,p'-DDE from 10(
      10) to 10(-7) M for 96 h markedly enhanced proliferations of human colorectal
      adenocarcinoma cell lines. Moreover, p,p'-DDE exposure could activate Wnt/beta
      catenin and Hedgehog/Gli1 signaling cascades, and the expression level of c-Myc
      and cyclin D1 was significantly increased. Consistently, p,p'-DDE-induced cell
      proliferation along with upregulated c-Myc and cyclin D1 were impeded by beta
      catenin siRNA or Gli1 siRNA. In addition, p,p'-DDE was able to activate NADPH
      oxidase, generate reactive oxygen species (ROS) and reduce GSH content,
      superoxide dismutase (SOD) and calatase (CAT) activities. Treatment with
      antioxidants prevented p,p'-DDE-induced cell proliferation and signaling pathways
      of Wnt/beta-catenin and Hedgehog/Gli1. These results indicated that p,p'-DDE
      promoted colorectal cancer cell proliferation through Wnt/beta-catenin and
      Hedgehog/Gli1 signalings mediated by oxidative stress. The finding suggests an
      association between p,p'-DDE exposure and the risk of colorectal cancer
      progression.

PMID- 25386962
TI  - Mandarin speech perception in combined electric and acoustic stimulation.
AB  - For deaf individuals with residual low-frequency acoustic hearing, combined use
      of a cochlear implant (CI) and hearing aid (HA) typically provides better speech
      understanding than with either device alone. Because of coarse spectral
      resolution, CIs do not provide fundamental frequency (F0) information that
      contributes to understanding of tonal languages such as Mandarin Chinese. The HA
      can provide good representation of F0 and, depending on the range of aided
      acoustic hearing, first and second formant (F1 and F2) information. In this
      study, Mandarin tone, vowel, and consonant recognition in quiet and noise was
      measured in 12 adult Mandarin-speaking bimodal listeners with the CI-only and
      with the CI+HA. Tone recognition was significantly better with the CI+HA in
      noise, but not in quiet. Vowel recognition was significantly better with the
      CI+HA in quiet, but not in noise. There was no significant difference in
      consonant recognition between the CI-only and the CI+HA in quiet or in noise.
      There was a wide range in bimodal benefit, with improvements often greater than
      20 percentage points in some tests and conditions. The bimodal benefit was
      compared to CI subjects' HA-aided pure-tone average (PTA) thresholds between 250
      and 2000 Hz; subjects were divided into two groups: "better" PTA (<50 dB HL) or
      "poorer" PTA (>50 dB HL). The bimodal benefit differed significantly between
      groups only for consonant recognition. The bimodal benefit for tone recognition
      in quiet was significantly correlated with CI experience, suggesting that bimodal
      CI users learn to better combine low-frequency spectro-temporal information from
      acoustic hearing with temporal envelope information from electric hearing. Given
      the small number of subjects in this study (n = 12), further research with
      Chinese bimodal listeners may provide more information regarding the contribution
      of acoustic and electric hearing to tonal language perception. 

PMID- 25386961
TI  - A physiologic role for serotonergic transmission in adult rat taste buds.
AB  - Of the multiple neurotransmitters and neuropeptides expressed in the mammalian
      taste bud, serotonin remains both the most studied and least understood.
      Serotonin is expressed in a subset of taste receptor cells that form synapses
      with afferent nerve fibers (type III cells) and was once thought to be essential
      to neurotransmission (now understood as purinergic). However, the discovery of
      the 5-HT1A serotonin receptor in a subset of taste receptor cells paracrine to
      type III cell suggested a role in cell-to-cell communication during the
      processing of taste information. Functional data describing this role are
      lacking. Using anatomical and neurophysiological techniques, this study proposes
      a modulatory role for serotonin during the processing of taste information.
      Double labeling immunocytochemical and single cell RT-PCR technique experiments
      documented that 5-HT1A-expressing cells co-expressed markers for type II cells,
      cells which express T1R or T2R receptors and release ATP. These cells did not co
      express type III cells markers. Neurophysiological recordings from the chorda
      tympani nerve, which innervates anterior taste buds, were performed prior to and
      during intravenous injection of a 5-HT1A receptor antagonist. These experiments
      revealed that serotonin facilitates processing of taste information for tastants
      representing sweet, sour, salty, and bitter taste qualities. On the other hand,
      injection of ondansetron, a 5-HT3 receptor antagonist, was without effect.
      Collectively, these data support the hypothesis that serotonin is a crucial
      element in a finely-tuned feedback loop involving the 5-HT1A receptor, ATP, and
      purinoceptors. It is hypothesized that serotonin facilitates gustatory signals by
      regulating the release of ATP through ATP-release channels possibly through
      phosphatidylinositol 4,5-bisphosphate resynthesis. By doing so, 5-HT1A activation
      prevents desensitization of post-synaptic purinergic receptors expressed on
      afferent nerve fibers and enhances the afferent signal. Serotonin may thus play a
      major modulatory role within peripheral taste in shaping the afferent taste
      signals prior to their transmission across gustatory nerves. 

PMID- 25386963
TI  - Prediction and control of brucellosis transmission of dairy cattle in Zhejiang
      Province, China.
AB  - Brucellosis is a bacterial disease caused by brucella; mainly spread by direct
      contact transmission through the brucella carriers, or indirect contact
      transmission by the environment containing large quantities of bacteria
      discharged by the infected individuals. At the beginning of 21st century, the
      epidemic among dairy cows in Zhejiang province, began to come back and has become
      a localized prevalent epidemic. Combining the pathology of brucellosis, the
      reported positive data characteristics, and the feeding method in Zhejiang
      province, this paper establishes an SEIV dynamic model to excavate the internal
      transmission dynamics, fit the real disease situation, predict brucellosis
      tendency and assess control measures in dairy cows. By careful analysis, we give
      some quantitative results as follows. (1) The external input of dairy cows from
      northern areas may lead to high fluctuation of the number of the infectious cows
      in Zhejiang province that can reach several hundreds. In this case, the disease
      cannot be controlled and the infection situation cannot easily be predicted.
      Thus, this paper encourages cows farms to insist on self-supplying production of
      the dairy cows. (2) The effect of transmission rate of brucella in environment to
      dairy cattle on brucellosis spreading is greater than transmission rate of the
      infectious dairy cattle to susceptible cattle. The prevalence of the epidemic is
      mainly aroused by environment transmission. (3) Under certain circumstances, the
      epidemic will become a periodic phenomenon. (4) For Zhejiang province, besides
      measures that have already been adopted, sterilization times of the infected
      regions is suggested as twice a week, and should be combined with management of
      the birth rate of dairy cows to control brucellosis spread.

PMID- 25386965
TI  - Immunogenicity and safety of inactivated quadrivalent and trivalent influenza
      vaccines in children 18-47 months of age.
AB  - BACKGROUND: Because inactivated trivalent influenza vaccines (TIVs) contain 1
      influenza B strain, whereas 2 lineages may co-circulate, B lineage mismatch is
      frequent. We assessed an inactivated quadrivalent influenza vaccine (QIV)
      containing both B lineages versus TIV in young children. METHODS: Children aged
      18-47 months who had received 2 doses of TIV in a study during the previous
      season (primed cohort, n = 192) were randomized 1:1 to receive 1 dose of TIV or
      QIV, and a further 407 children (unprimed cohort) were randomized 1:1 to receive
      2 doses of TIV or QIV 28 days apart. Immunogenicity was assessed by
      hemagglutination-inhibition (HI) prevaccination and 28 days after each
      vaccination. Immunogenic non-inferiority QIV versus TIV for shared strains, and
      superiority against the alternate-lineage B strain were based on HI geometric
      mean titers (pooled analyses of primed and half of unprimed cohort with Day 56
      immunogenicity assessment). Solicited and unsolicited adverse events were
      assessed during each 7- and 28-day postvaccination period, respectively
      (NCT00985790). RESULTS: Non-inferiority for shared strains and superiority for
      the alternate-lineage B strain unique to QIV was demonstrated for QIV versus TIV.
      QIV was immunogenic against all 4 vaccine strains and 87.0%, 88.6%, 69.8% and
      97.9% of children had postvaccination titers of >= 1:40 against A/H1N1, A/H3N2,
      B/Victoria and B/Yamagata, respectively. Reactogenicity and safety of QIV was
      consistent with TIV. CONCLUSIONS: QIV provided superior immunogenicity for the
      alternate-lineage B strain compared with TIV without interfering with immune
      responses to shared strains. Further studies are warranted to assess QIVs in
      children and to establish the clinical benefits of QIV versus TIV.

PMID- 25386966
TI  - Sources of pertussis infection in young babies from Sao Paulo State, Brazil.
AB  - Household contacts are important sources of Bordetella pertussis in infants. A
      total of 353 household contacts of 97 index cases were evaluated for pertussis by
      culture and polymerase chain reaction. Twenty eight contacts were positive
      (8.0%). The presence of symptoms did not influence the rate of diagnosed
      bacteriologic pertussis in communicants. We conclude that contacts with an index
      case can be positive for B. pertussis independently of the presence of symptoms. 

PMID- 25386964
TI  - Perception of human papillomavirus infection, cervical cancer and HPV vaccination
      in North Indian population.
AB  - BACKGROUND: Human Papillomavirus (HPV) -associated cervical cancer is the second
      most common cancer in women worldwide but it is the most frequent gynaecological
      cancer and cancer associated death in India women. The objective of this study
      was to assess knowledge about cervical cancer, HPV, HPV vaccine, HPV vaccine
      acceptance among school and undergraduates students and their parent's perception
      about acceptance of HPV vaccine in Northern part of India (Delhi and NCR
      regions). MATERIALS AND METHODS: A qualitative questionnaire based survey among
      2500 urban/rural students aged 12-22 years was conducted. RESULTS: Overall, a low
      frequency (15%) of HPV and cervical cancer awareness was observed in students and
      their parents. However, the awareness was much higher in females belonging to
      urban setup compared to boys with a perception that HPV causes cervical cancer in
      women only. Additionally, only (13%) participants who were aware of cervical
      cancer and HPV) were willing to accept HPV vaccination. Apparently, parents of
      female students were two times more willing to accept HPV vaccination for their
      ward than male students (p<0.001; OR 95%CI = 2.09 (1.58-2.76). CONCLUSION:
      Cervical cancer and HPV awareness among school, undergraduate students and also
      to their parents was found to be very low in this part of India. The level of
      awareness and education appears to be insignificant determinants in rural
      compared to urban setup. Better health education will be needed to maximize
      public awareness for cervical cancer prevention.

PMID- 25386967
TI  - A localized rash in a 3-year-old child.

PMID- 25386968
TI  - Safety of empiric outpatient treatment of suspected tick-borne infection in the
      pediatric emergency department.

PMID- 25386969
TI  - Sepsis and meningitis caused by Pasteurella multocida and echovirus 9 in a
      neonate.

PMID- 25386970
TI  - Diurnal temperature range related to respiratory tract infection in childhood.

PMID- 25386971
TI  - World Health Organization guidelines for childhood tuberculosis management:
      successes achieved and challenges ahead.

PMID- 25386972
TI  - Women scientist and the will to prevent Hib disease.

PMID- 25386974
TI  - The kinetics and mechanism of photo-assisted Ag(I)-catalysed water oxidation with
      S2O8(2-).
AB  - The kinetics of photo-assisted Ag(I)-catalysed water oxidation into O2 with
      S2O8(2-) has been investigated. When the concentration of Ag(+) is less than 7.06
      * 10(-3) mol L(-1), O2-evolution under visible light illumination (lambda>= 400
      nm) obeys the first-order rate law with respect to the concentrations of Ag(+)
      and S2O8(2-), respectively. The rate law is expressed as -dc(S2O8(2-))/dt =
      2dc(O2)/dt = kLc(S2O8(2-))c(Ag(+)), where kL is 12.4 +/- 1 mol(-1) L h(-1) at
      24.5  degrees C and the activation energy is 3.7 * 10(4) J mol(-1). It is found
      that visible light can improve the evolution of O2 remarkably. Compared with
      those without illumination, the rate constants under visible light are increased
      by ca. 3.8 mol(-1) L h(-1) at 4.5, 11.5, 17.5 and 24.5  degrees C, which are
      hardly affected by the reaction temperature. Employing MS/MS, ESR, XRD and UV
      visible spectroscopy, the intermediate species {AgS2O8}(-), Ag(2+), OH, Ag2O3 and
      AgO(+) in the process of water oxidation have been detected. Based on the
      experimental evidence, the mechanism of Ag(I)-catalysed water oxidation with
      S2O8(2-) has been developed, in which the reaction (AgO(+) + H2O -> Ag(+) + H2O2)
      is considered as the rate-determining step. The increase of the O2-evolution rate
      under visible light illumination results from the absorbance of the AgO(+)
      species at 375 nm, promoting the rate-determining step.

PMID- 25386975
TI  - Periodicity-induced symmetry breaking in a Fano lattice: hybridization and tight
      binding regimes.
AB  - We investigate experimentally and theoretically the role of periodicity on the
      optical response of dolmen plasmonic arrays that exhibit a Fano line shape.
      Contrary to previous works on single nanostructures, this study deals with the in
      plane near-field coupling between adjacent unit cells. By making an analogy to
      the electronic properties of atoms in the tight-binding model, specific behaviors
      of photonic states are investigated numerically as a function of the structural
      asymmetry for different coupling directions. These predictions are verified
      experimentally with dark-field measurements on nanostructure arrays which exhibit
      high tunability and fine control of their spectral features as a function of the
      lattice constants. These effects, originated from symmetry-breaking and selective
      excitation of the subradiant mode, provide additional degree of freedom for
      tuning the spectral response and can be used for the sensitive detection of local
      perturbations. This study provides a general understanding of the near-field
      interactions in Fano resonant lattices that can be used for the design of
      plasmonic nanostructures and planar metamaterials. 

PMID- 25386976
TI  - Where are supercentenarians located? A worldwide demographic study.
AB  - The world population is continuously aging, and centenarians may be considered to
      be the most successfully aged individuals. Among people who reach extreme
      longevity (EL; i.e., >95 years), supercentenarians (SCs; aged >=110 years)
      represent a subgroup of great scientific interest. Unfortunately, data on the
      worldwide distribution of SCs remain scarce. Therefore, this study was designed
      to investigate this issue. Current available data indicate that Japan is the
      country with the highest number of currently alive SCs. Interestingly, Puerto
      Rico would show the highest prevalence of SCs among people who reach EL
      (approximately one SC per 10,000 inhabitants aged >=95 years), although data on
      this country must be intrepreted with caution owing to potential methodological
      limitations, mainly related to its small population. Our findings highlight the
      need to investigate in greater detail the genetic and lifestyle background of
      SCs, with the ultimate goal of unraveling new potential mechanisms underlying
      human EL. 

PMID- 25386977
TI  - Garlic for the common cold.
AB  - Background Garlic is alleged to have antimicrobial and antiviral properties that
      relieve the common cold, among other beneficial effects. There is widespread
      usage of garlic supplements. The common cold is associated with significant
      morbidity and economic consequences. On average, children have six to eight colds
      per year and adults have two to four.Objectives To determine whether garlic
      (Allium sativum) is effective for the prevention or treatment of the common cold,
      when compared to placebo, no treatment or other treatments.Search methods We
      searched CENTRAL (2014, Issue 7),OLDMEDLINE (1950 to 1965),MEDLINE (January 1966
      to July week 5, 2014), EMBASE(1974 to August 2014) and AMED (1985 to August
      2014).Selection criteria Randomised controlled trials of common cold prevention
      and treatment comparing garlic with placebo, no treatment or standard
      treatment.Data collection and analysis Two review authors independently reviewed
      and selected trials from searches, assessed and rated study quality and extracted
      relevant data.Main results In this updated review, we identified eight trials as
      potentially relevant from our searches. Again, only one trial met the inclusion
      criteria.This trial randomly assigned 146 participants to either a garlic
      supplement (with 180 mg of allicin content) or a placebo (once daily)for 12
      weeks. The trial reported 24 occurrences of the common cold in the garlic
      intervention group compared with 65 in the placebo group (P value < 0.001),
      resulting in fewer days of illness in the garlic group compared with the placebo
      group (111 versus 366). The number of days to recovery from an occurrence of the
      common cold was similar in both groups (4.63 versus 5.63). Only one trial met the
      inclusion criteria, therefore limited conclusions can be drawn. The trial relied
      on self reported episodes of the common cold but was of reasonable quality in
      terms of randomisation and allocation concealment. Adverse effects included rash
      and odour. Authors' conclusions There is insufficient clinical trial evidence
      regarding the effects of garlic in preventing or treating the common cold. A
      single trial suggested that garlic may prevent occurrences of the common cold but
      more studies are needed to validate this finding. Claims of effectiveness appear
      to rely largely on poor-quality evidence.

PMID- 25386978
TI  - Editorial--in this issue: innate immunity in normal and pathologic circumstances.
AB  - In this issue of the International Reviews of Immunology, we host several reviews
      dedicated to the innate immunity in normal and diseased states. Tan et al.
      discuss the molecular nature of the innate immune response as a consequence of co
      engagement of distinct Toll-like receptors. Schwarz et al. present a regulatory
      loop leading to increased myelopoiesis through the engagement of CD137L by CD137+
      T cells. Kolandaswamy et al. present transcriptomic evidence that distinguishes
      between two major subsets of monocytes. In a different review, Minasyan presents
      an interesting hypothesis that erythrocytes have a dominant role in clearing
      bacteria within the blood stream while leukocytes' role is mostly extra-vascular.
      Yan et al. discuss the pivotal role of the liver, its pre-existing and associated
      pathology, in sepsis. Zhang outlines the implications of declining neutrophils
      and impact to long-term management of HIV-associated disease. Finally, Lal et al.
      discuss the multiple roles of gammadeltaT cells in innate and adaptive immunity. 

PMID- 25386979
TI  - Mode of exercise and sex are not important for oxygen consumption during and in
      recovery from sprint interval training.
AB  - Most sprint interval training (SIT) research involves cycling as the mode of
      exercise and whether running SIT elicits a similar excess postexercise oxygen
      consumption (EPOC) response to cycling SIT is unknown. As running is a more whole
      body-natured exercise, the potential EPOC response could be greater when using a
      running session compared with a cycling session. The purpose of the current study
      was to determine the acute effects of a running versus cycling SIT session on
      EPOC and whether potential sex differences exist. Sixteen healthy recreationally
      active individuals (8 males and 8 females) had their gas exchange measured over
      ~2.5 h under 3 experimental sessions: (i) a cycle SIT session, (ii) a run SIT
      session, and (iii) a control (CTRL; no exercise) session. Diet was controlled.
      During exercise, both SIT modes increased oxygen consumption (cycle: male, 1.967
      +/- 0.343; female, 1.739 +/- 0.296 L.min(-1); run: male, 2.169 +/- 0.369; female,
      1.791 +/- 0.481 L.min(-1)) versus CTRL (male, 0.425 +/- 0.065 L.min(-1); female,
      0.357 +/- 0.067; P < 0.001), but not compared with each other (P = 0.234). In the
      first hour postexercise, oxygen consumption was still increased following both
      run (male, 0.590 +/- 0.065; female, 0.449 +/- 0.084) and cycle SIT (male, 0.556
      +/- 0.069; female, 0.481 +/- 0.110 L.min(-1)) versus CTRL and oxygen consumption
      was maintained through the second hour postexercise (CTRL: male, 0.410 +/- 0.048;
      female, 0.332 +/- 0.062; cycle: male, 0.430 +/- 0.047; female, 0.395 +/- 0.087;
      run: male, 0.463 +/- 0.051; female, 0.374 +/- 0.087 L.min(-1)). The total EPOC
      was not significantly different between modes of exercise or males and females (P
      > 0.05). Our data demonstrate that the mode of exercise during SIT (cycling or
      running) is not important to O2 consumption and that males and females respond
      similarly. 

PMID- 25386980
TI  - Effects of winter military training on energy balance, whole-body protein
      balance, muscle damage, soreness, and physical performance.
AB  - Physiological consequences of winter military operations are not well described.
      This study examined Norwegian soldiers (n = 21 males) participating in a
      physically demanding winter training program to evaluate whether short-term
      military training alters energy and whole-body protein balance, muscle damage,
      soreness, and performance. Energy expenditure (D2(18)O) and intake were measured
      daily, and postabsorptive whole-body protein turnover ([(15)N]-glycine), muscle
      damage, soreness, and performance (vertical jump) were assessed at baseline,
      following a 4-day, military task training phase (MTT) and after a 3-day, 54-km
      ski march (SKI). Energy intake (kcal.day(-1)) increased (P < 0.01) from (mean +/-
      SD (95% confidence interval)) 3098 +/- 236 (2985, 3212) during MTT to 3461 +/-
      586 (3178, 3743) during SKI, while protein (g.kg(-1).day(-1)) intake remained
      constant (MTT, 1.59 +/- 0.33 (1.51, 1.66); and SKI, 1.71 +/- 0.55 (1.58, 1.85)).
      Energy expenditure increased (P < 0.05) during SKI (6851 +/- 562 (6580, 7122))
      compared with MTT (5480 +/- 389 (5293, 5668)) and exceeded energy intake. Protein
      flux, synthesis, and breakdown were all increased (P < 0.05) 24%, 18%, and 27%,
      respectively, during SKI compared with baseline and MTT. Whole-body protein
      balance was lower (P < 0.05) during SKI (-1.41 +/- 1.11 (-1.98, -0.84) g.kg(
      1).10 h) than MTT and baseline. Muscle damage and soreness increased and
      performance decreased progressively (P < 0.05). The physiological consequences
      observed during short-term winter military training provide the basis for future
      studies to evaluate nutritional strategies that attenuate protein loss and
      sustain performance during severe energy deficits. 

PMID- 25386981
TI  - Folate, vitamin B12, and vitamin B6 status of a group of high socioeconomic
      status women in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort.
AB  - Folic acid supplementation and food fortification policies have improved folate
      status in North American women of child bearing age. Recent studies have reported
      the possible inadequacy of vitamin B12 and B6 in the etiology of neural tube
      defects in folate-fortified populations. The aims of this study were to describe
      folate status and its relationship to supplementation and to assess vitamin B12
      and B6 status in a cohort of pregnant women. Supplement intake data were
      collected in each trimester from the first cohort (n = 599) of the Alberta
      Pregnancy Outcomes and Nutrition (APrON) study. Red blood cell folate (RBCF) and
      plasma folate, holotranscobalamin, and pyridoxal 5-phosphate were measured. Overt
      folate deficiency was rare (3%) but 24% of women in their first trimester had
      suboptimal RBCF concentration (<906 nmol.L(-1)). The proportion of the cohort in
      this category declined substantially in second (9%) and third (7%) trimesters.
      High RBCF (>1360 nmol.L(-1)) was observed in approximately half of the women
      during each pregnancy trimester. Vitamin B12 and B6 deficiencies were rare (<1%
      of the cohort). Women consuming folic acid supplements above the upper level had
      significantly higher RBCF and plasma folate concentrations. In conclusion, the
      prevalence of vitamin B12 and B6 deficiency was very low. A quarter of the women
      had suboptimal folate status in the first trimester of pregnancy and over half
      the women had abnormally high RBCF, suggesting that supplementation during
      pregnancy is not appropriate in a cohort of women considered to be healthy and a
      low risk for nutritional deficiencies. 

PMID- 25386984
TI  - The test-retest reliability of knee joint center location techniques.
AB  - The principal source of measurement error in three-dimensional analyses is the
      definition of the joint center about which segmental rotations occur. The hip
      joint has received considerable attention in three-dimensional modeling analyses
      yet the reliability of the different techniques for the definition of the knee
      joint center has yet to be established. This study investigated the reliability
      of five different knee joint center estimation techniques: femoral epicondyle,
      femoral condyle, tibial ridge, plugin- gait, and functional. Twelve male
      participants walked at 1.25 m.s-1 and three-dimensional kinetics/kinematics of
      the knee and ankle were collected. The knee joint center was defined twice using
      each technique (test-and-retest) and the joint kinetic/kinematic data were
      applied to both. Wilcoxon rank tests and intraclass correlation coefficients
      (ICCs) were used to compare test and retest angular parameters and kinematic
      waveforms. The results show significant differences in coronal and transverse
      planes angulation using the tibial ridge, plug-in-gait, and functional methods.
      The strongest test-retest ICCs were observed for the femoral epicondyle and
      femoral condyle configurations. The findings from the current investigation
      advocate that the femoral epicondyle and femoral condyle techniques for the
      estimation of the knee joint center are currently the most reliable techniques. 

PMID- 25386983
TI  - Genetic, epigenetic, and HPLC fingerprint differentiation between natural and ex
      situ populations of Rhodiola sachalinensis from Changbai Mountain, China.
AB  - Rhodiola sachalinensis is an endangered species with important medicinal value.
      We used inter-simple sequence repeat (ISSR) and methylation-sensitive amplified
      polymorphism (MSAP) markers to analyze genetic and epigenetic differentiation in
      different populations of R. sachalinensis, including three natural populations
      and an ex situ population. Chromatographic fingerprint was used to reveal HPLC
      fingerprint differentiation. According to our results, the ex situ population of
      R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint
      variation than natural populations, but shows lower epigenetic diversity. Most
      genetic variation (54.88%) was found to be distributed within populations, and
      epigenetic variation was primarily distributed among populations (63.87%). UPGMA
      cluster analysis of ISSR and MSAP data showed identical results, with individuals
      from each given population grouping together. The results of UPGMA cluster
      analysis of HPLC fingerprint patterns was significantly different from results
      obtained from ISSR and MSAP data. Correlation analysis revealed close
      relationships among altitude, genetic structure, epigenetic structure, and HPLC
      fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90
      for DNA methylation level and altitude; R2 = -0.95 for HPLC fingerprint and
      altitude). Taken together, our results indicate that ex situ population of R.
      sachalinensis show significantly different genetic and epigenetic population
      structures and HPLC fingerprint patterns. Along with other potential
      explanations, these findings suggest that the ex situ environmental factors
      caused by different altitude play an important role in keeping hereditary
      characteristic of R. sachalinensis. 

PMID- 25386986
TI  - Reduction of diffusive contaminant emissions from a dissolved source in a lower
      permeability layer by sodium persulfate treatment.
AB  - Residual contamination contained in lower permeability zones is difficult to
      remediate and can, through diffusive emissions to adjacent higher permeability
      zones, result in long-term impacts to groundwater. This work investigated the
      effectiveness of oxidant delivery for reducing diffusive emissions from lower
      permeability zones. The experiment was conducted in a 1.2 m tall * 1.2 m wide * 6
      cm thick tank containing two soil layers having 3 orders of magnitude contrast in
      hydraulic conductivity. The lower permeability layer initially contained
      dissolved methyl tert-butyl ether (MTBE) and benzene, toluene, ethylbenzene, and
      p-xylenes (BTEX). The treatment involved delivery of 10% w/w nonactivated sodium
      persulfate (Na2S2O8) solution to the high permeability layer for 14 days. The
      subsequent diffusion into the lower permeability layer and contaminant emission
      response were monitored for about 240 days. The S2O8(2-) diffused about 14 cm at
      1% w/w into the lower permeability layer during the 14 day delivery and continued
      diffusing deeper into the layer as well as back toward the higher-lower
      permeability interface after delivery ceased. Over 209 days, the S2O8(2-)
      diffused 60 cm into the lower permeability layer, the BTEX mass and emission rate
      were reduced by 95-99%, and the MTBE emission rate was reduced by 63%. The
      overall treatment efficiency was about 60-110 g-S2O8(2-)delivered/g-hydrocarbon
      oxidized, with a significant fraction of the oxidant delivered likely lost by
      back-diffusion and not involved in hydrocarbon destruction. 

PMID- 25386987
TI  - Structurally diverse alpha-substituted benzopyran synthesis through a practical
      metal-free C(sp3)-H functionalization.
AB  - A trityl ion-mediated practical C-H functionalization of a variety of benzopyrans
      with a wide range of nucleophiles (organoboranes and C-H molecules) at ambient
      temperature has been disclosed. The metal-free reaction has an excellent
      functional group tolerance and high chemoselectivity and displays a broad scope
      with respect to both benzopyran and nucleophile partners, efficiently affording a
      collection of benzopyrans bearing diverse skeletons and alpha-functionalities in
      one step. 

PMID- 25386988
TI  - Glia talk back.

PMID- 25386989
TI  - Homeostatic control of presynaptic neurotransmitter release.
AB  - It is well established that the active properties of nerve and muscle cells are
      stabilized by homeostatic signaling systems. In organisms ranging from Drosophila
      to humans, neurons restore baseline function in the continued presence of
      destabilizing perturbations by rebalancing ion channel expression, modifying
      neurotransmitter receptor surface expression and trafficking, and modulating
      neurotransmitter release. This review focuses on the homeostatic modulation of
      presynaptic neurotransmitter release, termed presynaptic homeostasis. First, we
      highlight criteria that can be used to define a process as being under
      homeostatic control. Next, we review the remarkable conservation of presynaptic
      homeostasis at the Drosophila, mouse, and human neuromuscular junctions and
      emerging parallels at synaptic connections in the mammalian central nervous
      system. We then highlight recent progress identifying cellular and molecular
      mechanisms. We conclude by reviewing emerging parallels between the mechanisms of
      homeostatic signaling and genetic links to neurological disease. 

PMID- 25386991
TI  - Intrinsic and extrinsic mechanisms of dendritic morphogenesis.
AB  - The complex, branched morphology of dendrites is a cardinal feature of neurons
      and has been used as a criterion for cell type identification since the beginning
      of neurobiology. Regulated dendritic outgrowth and branching during development
      form the basis of receptive fields for neurons and are essential for the wiring
      of the nervous system. The cellular and molecular mechanisms of dendritic
      morphogenesis have been an intensely studied area. In this review, we summarize
      the major experimental systems that have contributed to our understandings of
      dendritic development as well as the intrinsic and extrinsic mechanisms that
      instruct the neurons to form cell type-specific dendritic arbors. 

PMID- 25386993
TI  - Urban-rural differentials in overweight and obese individuals with diarrhea in
      bangladesh.
AB  - OBJECTIVE: The study aimed to determine urban and rural differences in overweight
      and obesity (OO) with diarrhea regarding subjects' sociodemographic, clinical
      characteristics, etiology, and antimicrobial susceptibility. METHODS: Relevant
      information from 2000 to 2011 were extracted from the data archive of the
      Diarrheal Disease Surveillance System of urban Dhaka (1248, 4.5%) and rural
      Matlab (615, 3.4%) hospitals of the International Centre for Diarrheal Disease
      Research, Bangladesh (icddr,b). RESULTS: The proportion of OO significantly
      increased in both urban (3-7%; chi-square for trend p < 0.001) and rural (1-6%; p
      < 0.001) areas over the study period. In multivariate modeling, monthly income
      more than US$100 (odds ratio [OR] = 54.44, 95% confidence interval [CI], 25.37
      116.82, p < 0.001), high wealth quintile (OR = 18.23, 95% CI, 8.63-38.49, p <
      0.001), access to sanitary toilet (OR = 3.07. 95% CI. 1.76-5.26. p < 0.001),
      boiled drinking water (OR = 2.77, 95% CI, 1.09-7.05, p = 0.032), antimicrobial
      use before hospitalization (OR = 4.99, 95% CI, 2.85-8.74, p < 0.001), fever (OR =
      0.14, 95% CI, 0.37, 0.50, p < 0.001), watery stools (OR = 5.59, 95% CI, 2.11
      14.80, p < 0.001), dehydrating diarrhea (OR = 5.17, 95% CI, 2.54-10.52, p <
      0.001), intravenous saline infusion after hospitalization (OR = 2.65, 95% CI,
      1.28-5.49, p = 0.009), and Salmonella infection (OR = 0.20, 95% CI, 0.50-0.83, p
      = 0.027) remained significantly associated with urban OO individuals. At least
      88% of Shigella isolates were susceptible to ciprofloxacin in both urban and
      rural areas; for mecillinum it was 90%. Ciprofloxacin had the least detected
      resistance for Vibrio cholerae (0%) and trimethoprim-sulfamethoxazole (TMP-SMX)
      showed the greatest resistance (Dhaka 86%; Matlab 98%). Susceptibility for
      Salmonella showed ampicillin (95%), chloramphenecol (100%), ciprofloxacin (95%),
      ceftraxone (93%), TMP-SMX (95%) at both sites. CONCLUSION: Urban OO with
      diarrheal illnesses was significantly different from that in rural areas,
      including antimicrobial susceptibility.

PMID- 25386990
TI  - Cilia dysfunction in lung disease.
AB  - A characteristic feature of the human airway epithelium is the presence of
      ciliated cells bearing motile cilia, specialized cell surface projections
      containing axonemes composed of microtubules and dynein arms, which provide ATP
      driven motility. In the airways, cilia function in concert with airway mucus to
      mediate the critical function of mucociliary clearance, cleansing the airways of
      inhaled particles and pathogens. The prototypical disorder of respiratory cilia
      is primary ciliary dyskinesia, an inherited disorder that leads to impaired
      mucociliary clearance, to repeated chest infections, and to the progressive
      destruction of lung architecture. Numerous acquired lung diseases are also marked
      by abnormalities in both cilia structure and function. In this review we
      summarize current knowledge regarding airway ciliated cells and cilia, how they
      function to maintain a healthy epithelium, and how disorders of cilia structure
      and function contribute to inherited and acquired lung disease. 

PMID- 25386994
TI  - Protease activated receptor-2 (PAR2): possible target of phytochemicals.
AB  - The use of phytochemicals either singly or in combination with other anticancer
      drugs comes with an advantage of less toxicity and minimal side effects.
      Signaling pathways play central role in cell cycle, cell growth, metabolism, etc.
      Thus, the identification of phytochemicals with promising antagonistic effect on
      the receptor/s playing key role in single transduction may have better
      therapeutic application. With this background, phytochemicals were screened
      against protease-activated receptor 2 (PAR2). PAR2 belongs to the superfamily of
      GPCRs and is an important target for breast cancer. Using in silico methods, this
      study was able to identify the phytochemicals with promising binding affinity
      suggesting their therapeutic potential in the treatment of breast cancer. The
      findings from this study acquires importance as the information on the possible
      agonists and antagonists of PAR2 is limited due its unique mechanism of
      activation. 

PMID- 25386992
TI  - Regeneration and repair of the exocrine pancreas.
AB  - Pancreatitis is caused by inflammatory injury to the exocrine pancreas, from
      which both humans and animal models appear to recover via regeneration of
      digestive enzyme-producing acinar cells. This regenerative process involves
      transient phases of inflammation, metaplasia, and redifferentiation, driven by
      cell-cell interactions between acinar cells, leukocytes, and resident
      fibroblasts. The NFkappaB signaling pathway is a critical determinant of
      pancreatic inflammation and metaplasia, whereas a number of developmental signals
      and transcription factors are devoted to promoting acinar redifferentiation after
      injury. Imbalances between these proinflammatory and prodifferentiation pathways
      contribute to chronic pancreatitis, characterized by persistent inflammation,
      fibrosis, and acinar dedifferentiation. Loss of acinar cell differentiation also
      drives pancreatic cancer initiation, providing a mechanistic link between
      pancreatitis and cancer risk. Unraveling the molecular bases of exocrine
      regeneration may identify new therapeutic targets for treatment and prevention of
      both of these deadly diseases. 

PMID- 25386995
TI  - Percutaneous Clinical T1a Renal Mass Ablation in the Octogenarian and
      Nonagenarian: Oncologic Outcomes and Morbidity.
AB  - PURPOSE: To evaluate outcomes of percutaneous ablation of small renal tumors in
      the elderly population. PATIENTS AND METHODS: Using our tumor ablation database,
      we searched for percutaneous ablation procedures for clinical T1a renal masses in
      octogenarians and nonagenarians between June 2001 and May 2012. Altogether, 105
      tumors from 99 procedures among 95 patients (mean age 84.0+/-3.0 years, range 80
      92) were identified. Oncologic outcomes and major complications were evaluated.
      Assessment also included patient hospital stays and renal functional outcomes.
      RESULTS: Technical success was achieved in 60/61 (98.4%) tumors managed with
      cryoablation and 43/44 (97.7%) after radiofrequency ablation (RFA). Of 87 renal
      tumors with at least 3 months imaging follow-up, 2 (5.4%) tumors progressed at
      1.2 and 2.2 years after RFA. None recurred after cryoablation. Estimated
      progression-free survival rates at 1, 3, and 5 years after ablation were 99%,
      97%, and 97%, respectively. Thirty-four patients died at a mean of 3.7 years
      after ablation (median 3.7; range 0.4-9.6). Estimated overall survival rates were
      98%, 83%, and 61%, respectively. Among 33 patients with sporadic, biopsy-proven
      renal-cell carcinoma, estimated cancer-specific survival rates were 100%, 100%,
      and 86%, respectively. Five (8.6%) major complications developed after renal
      cryoablation with no (0%) major complication after RFA. Mean decrease in serum
      creatinine level within 1 week after ablation was 0.1 mg/dL. Mean hospitalization
      was 1.2 days. CONCLUSION: Percutaneous thermal ablation is safe and effective in
      the active management of clinical T1a renal masses in elderly patients. These
      results should help urologists appropriately assess expected outcomes when
      counseling octogenarian and nonagenarian patients.

PMID- 25386997
TI  - Tetraazaacenes containing four-membered rings in different oxidation states. Are
      they aromatic? A computational study.
AB  - A symmetrical tetraazaacene incorporating a central cyclobutadiene ring was
      calculated in different oxidation (hydrogenation) states, displaying different
      tautomers and conformers. Geometries, thermodynamics, and electronic properties
      were computed, and the aromaticity of all these species was calculated on a per
      ring basis by NICS-scans and NICS-X-scans. The results unveil unexpected and
      fascinating insights into the complex aromaticity of those compounds, including a
      formally aromatic (!) cyclobutadiene ring. 

PMID- 25386998
TI  - Polymeric actuators.
AB  - Actuators are materials and devices that are able to change their shape in
      response to changes in environmental conditions and perform mechanical work on
      nano-, micro-, and macroscales. Among the huge variety of different actuators,
      polymer-based ones are highly attractive because of a number of properties such
      as sensitivity to a broad range of stimuli and good mechanical properties. The
      goal of this review is to provide a general picture of different mechanisms and
      working principles of polymeric actuators as well as to show a palette of their
      applications. 

PMID- 25386999
TI  - Positron range in PET imaging: non-conventional isotopes.
AB  - In addition to conventional short-lived radionuclides, longer-lived isotopes are
      becoming increasingly important to positron emission tomography (PET). The longer
      half-life both allows for circumvention of the in-house production of
      radionuclides, and expands the spectrum of physiological processes amenable to
      PET imaging, including processes with prohibitively slow kinetics for
      investigation with short-lived radiotracers. However, many of these radionuclides
      emit 'high-energy' positrons and gamma rays which affect the spatial resolution
      and quantitative accuracy of PET images. The objective of the present work is to
      investigate the positron range distribution for some of these long-lived
      isotopes. Based on existing Monte Carlo simulations of positron interactions in
      water, the probability distribution of the line of response displacement have
      been empirically described by means of analytic displacement functions. Relevant
      distributions have been derived for the isotopes (22)Na, (52)Mn, (89)Zr, (45)Ti,
      (51)Mn, (94 m)Tc, (52 m)Mn, (38)K, (64)Cu, (86)Y, (124)I, and (120)I. It was
      found that the distribution functions previously found for a series of
      conventional isotopes (Jodal et al 2012 Phys. Med. Bio. 57 3931-43), were also
      applicable to these non-conventional isotopes, except that for (120)I, (124)I,
      (89)Zr, (52)Mn, and (64)Cu, parameters in the formulae were less well predicted
      by mean positron energy alone. Both conventional and non-conventional range
      distributions can be described by relatively simple analytic expressions. The
      results will be applicable to image-reconstruction software to improve the
      resolution.

PMID- 25387000
TI  - Von Willebrand factor is elevated in individuals infected with Sudan virus and is
      associated with adverse clinical outcomes.
AB  - Sudan virus (SUDV) is a member of the Filoviridae family that has been associated
      with sporadic outbreaks of human disease in sub-Saharan Africa. The filoviruses
      are notable for the high frequencies with which they cause both hemorrhagic
      manifestations and death in infected individuals. Recently, we reported an
      extensive biomarker analysis of patient specimens from the Gulu SUDV outbreak. In
      that study, we found evidence of endothelial dysfunction and alterations of
      factors important to the coagulation pathways. The complex intersection between
      the endothelium, coagulation, and immunity is further explored in this study
      where we examine several additional biomarkers using the same patient specimens.
      We report that von Willebrand factor (vWF), a protein that promotes platelet
      adhesion to the injured endothelium, is elevated in SUDV-infected individuals
      compared to normally reported values in healthy individuals. Furthermore, vWF is
      associated with a fatal outcome in SUDV-infected pediatric patients. In addition,
      we find that vWF is elevated in individuals who have hemorrhagic manifestations
      of disease, suggesting excessive thrombosis in these patients.

PMID- 25387001
TI  - Interventions for improving upper limb function after stroke.
AB  - BACKGROUND: Improving upper limb function is a core element of stroke
      rehabilitation needed to maximise patient outcomes and reduce disability.
      Evidence about effects of individual treatment techniques and modalities is
      synthesised within many reviews. For selection of effective rehabilitation
      treatment, the relative effectiveness of interventions must be known. However, a
      comprehensive overview of systematic reviews in this area is currently lacking.
      OBJECTIVES: To carry out a Cochrane overview by synthesising systematic reviews
      of interventions provided to improve upper limb function after stroke. METHODS: 
      SEARCH METHODS: We comprehensively searched the Cochrane Database of Systematic
      Reviews; the Database of Reviews of Effects; and PROSPERO (an international
      prospective register of systematic reviews) (June 2013). We also contacted review
      authors in an effort to identify further relevant reviews. SELECTION CRITERIA: We
      included Cochrane and non-Cochrane reviews of randomised controlled trials (RCTs)
      of patients with stroke comparing upper limb interventions with no treatment,
      usual care or alternative treatments. Our primary outcome of interest was upper
      limb function; secondary outcomes included motor impairment and performance of
      activities of daily living. When we identified overlapping reviews, we
      systematically identified the most up-to-date and comprehensive review and
      excluded reviews that overlapped with this. DATA COLLECTION AND ANALYSIS: Two
      overview authors independently applied the selection criteria, excluding reviews
      that were superseded by more up-to-date reviews including the same (or similar)
      studies. Two overview authors independently assessed the methodological quality
      of reviews (using a modified version of the AMSTAR tool) and extracted data.
      Quality of evidence within each comparison in each review was determined using
      objective criteria (based on numbers of participants, risk of bias, heterogeneity
      and review quality) to apply GRADE (Grades of Recommendation, Assessment,
      Development and Evaluation) levels of evidence. We resolved disagreements through
      discussion. We systematically tabulated the effects of interventions and used
      quality of evidence to determine implications for clinical practice and to make
      recommendations for future research. MAIN RESULTS: Our searches identified 1840
      records, from which we included 40 completed reviews (19 Cochrane; 21 non
      Cochrane), covering 18 individual interventions and dose and setting of
      interventions. The 40 reviews contain 503 studies (18,078 participants). We
      extracted pooled data from 31 reviews related to 127 comparisons. We judged the
      quality of evidence to be high for 1/127 comparisons (transcranial direct current
      stimulation (tDCS) demonstrating no benefit for outcomes of activities of daily
      living (ADLs)); moderate for 49/127 comparisons (covering seven individual
      interventions) and low or very low for 77/127 comparisons.Moderate-quality
      evidence showed a beneficial effect of constraint-induced movement therapy
      (CIMT), mental practice, mirror therapy, interventions for sensory impairment,
      virtual reality and a relatively high dose of repetitive task practice,
      suggesting that these may be effective interventions; moderate-quality evidence
      also indicated that unilateral arm training may be more effective than bilateral
      arm training. Information was insufficient to reveal the relative effectiveness
      of different interventions.Moderate-quality evidence from subgroup analyses
      comparing greater and lesser doses of mental practice, repetitive task training
      and virtual reality demonstrates a beneficial effect for the group given the
      greater dose, although not for the group given the smaller dose; however tests
      for subgroup differences do not suggest a statistically significant difference
      between these groups. Future research related to dose is essential.Specific
      recommendations for future research are derived from current evidence. These
      recommendations include but are not limited to adequately powered, high-quality
      RCTs to confirm the benefit of CIMT, mental practice, mirror therapy, virtual
      reality and a relatively high dose of repetitive task practice; high-quality RCTs
      to explore the effects of repetitive transcranial magnetic stimulation (rTMS),
      tDCS, hands-on therapy, music therapy, pharmacological interventions and
      interventions for sensory impairment; and up-to-date reviews related to
      biofeedback, Bobath therapy, electrical stimulation, reach-to-grasp exercise,
      repetitive task training, strength training and stretching and positioning.
      AUTHORS' CONCLUSIONS: Large numbers of overlapping reviews related to
      interventions to improve upper limb function following stroke have been
      identified, and this overview serves to signpost clinicians and policy makers
      toward relevant systematic reviews to support clinical decisions, providing one
      accessible, comprehensive document, which should support clinicians and policy
      makers in clinical decision making for stroke rehabilitation.Currently, no high
      quality evidence can be found for any interventions that are currently used as
      part of routine practice, and evidence is insufficient to enable comparison of
      the relative effectiveness of interventions. Effective collaboration is urgently
      needed to support large, robust RCTs of interventions currently used routinely
      within clinical practice. Evidence related to dose of interventions is
      particularly needed, as this information has widespread clinical and research
      implications.

PMID- 25387002
TI  - Enantiomerically enriched tris(boronates): readily accessible conjunctive
      reagents for asymmetric synthesis.
AB  - The catalytic enantioselective diboration of vinyl boronate esters furnishes
      chiral tris(boronates) in a selective fashion. Subsequent deborylative alkylation
      occurs in a diastereoselective fashion, both for intermolecular and
      intramolecular processes. 

PMID- 25387003
TI  - Quantitative carbon detector (QCD) for calibration-free, high-resolution
      characterization of complex mixtures.
AB  - Current research of complex chemical systems, including biomass pyrolysis,
      petroleum refining, and wastewater remediation requires analysis of large analyte
      mixtures (>100 compounds). Quantification of each carbon-containing analyte by
      existing methods (flame ionization detection) requires extensive identification
      and calibration. In this work, we describe an integrated microreactor system
      called the Quantitative Carbon Detector (QCD) for use with current gas
      chromatography techniques for calibration-free quantitation of analyte mixtures.
      Combined heating, catalytic combustion, methanation and gas co-reactant mixing
      within a single modular reactor fully converts all analytes to methane (>99.9%)
      within a thermodynamic operable regime. Residence time distribution of the QCD
      reveals negligible loss in chromatographic resolution consistent with fine
      separation of complex mixtures including cellulose pyrolysis products. 

PMID- 25387004
TI  - Epithelial MUC1 promotes cell migration, reduces apoptosis and affects levels of
      mucosal modulators during acetylsalicylic acid (aspirin)-induced gastropathy.
AB  - MUC1 is a transmembrane mucin highly expressed in the stomach. Although extensive
      research has uncovered many of its roles in cancer, knowledge about the functions
      of MUC1 in normal tissues is limited. In the present study, we showed that
      acetylsalicylic acid (ASA; aspirin) up-regulated MUC1/Muc1 expression in the
      gastric mucosa of humans and wild-type (WT) mice. ASA induced mucosal injury in
      all mice to a similar extent; however, WT animals and those chimaeras with Muc1
      on the epithelia recovered faster than Muc1-knockout (KO) mice and chimaeras
      carrying Muc1 on haemopoietic but not epithelial cells. MUC1 enhanced
      proliferation and migration of the human gastric cell line MKN-7 and increased
      resistance to apoptosis. The repeated treatment regime used caused a reduction in
      cyclo-oxygenase-1 (Cox-1) expression, though WT animals returned faster towards
      pre-treatment levels and had increased Cox-2 and vascular endothelial growth
      factor levels during recovery. Thus we found that epithelial Muc1 is more
      important for the healing process than haemopoietic Muc1 and Muc1/MUC1
      facilitates wound healing by enhancing cell migration and proliferation,
      protecting against apoptosis and mediating expression of mucosal modulators. Thus
      MUC1 plays essential roles during wound healing and development of treatment
      modalities targeting enhanced expression of MUC1 may be beneficial to treat
      mucosal wounds. 

PMID- 25387005
TI  - Uncovering the origins of a niche.
AB  - Multiple cell types that share a common origin cooperate to form a supportive
      niche for stem cells that give rise to blood and to the cells of the immune
      system. 

PMID- 25387006
TI  - Addgene: making materials sharing "science as usual".
AB  - Addgene (www.addgene.org) is a nonprofit organization that facilitates biomedical
      research and discovery by improving access to useful research materials and
      information. To fulfill this mission, Addgene works with hundreds of laboratories
      all over the world to collect high-quality published plasmids and data for the
      repository that can then be distributed to academic institutions and used to
      further research. Biological resource centers such as Addgene are an important
      part of the scientific infrastructure. They play a key role in helping scientists
      overcome logistical barriers to sharing, improving experimental reproducibility,
      and optimizing use of limited resources. 

PMID- 25387007
TI  - Analysis of nidogen-1/laminin gamma1 interaction by cross-linking, mass
      spectrometry, and computational modeling reveals multiple binding modes.
AB  - We describe the detailed structural investigation of nidogen-1/laminin gamma1
      complexes using full-length nidogen-1 and a number of laminin gamma1 variants.
      The interactions of nidogen-1 with laminin variants gamma1 LEb2-4, gamma1 LEb2-4
      N836D, gamma1 short arm, and gamma1 short arm N836D were investigated by applying
      a combination of (photo-)chemical cross-linking, high-resolution mass
      spectrometry, and computational modeling. In addition, surface plasmon resonance
      and ELISA studies were used to determine kinetic constants of the nidogen
      1/laminin gamma1 interaction. Two complementary cross-linking strategies were
      pursued to analyze solution structures of laminin gamma1 variants and nidogen-1.
      The majority of distance information was obtained with the homobifunctional amine
      reactive cross-linker bis(sulfosuccinimidyl)glutarate. In a second approach, UV
      induced cross-linking was performed after incorporation of the diazirine
      containing unnatural amino acids photo-leucine and photo-methionine into laminin
      gamma1 LEb2-4, laminin gamma1 short arm, and nidogen-1. Our results indicate that
      Asn-836 within laminin gamma1 LEb3 domain is not essential for complex formation.
      Cross-links between laminin gamma1 short arm and nidogen-1 were found in all
      protein regions, evidencing several additional contact regions apart from the
      known interaction site. Computational modeling based on the cross-linking
      constraints indicates the existence of a conformational ensemble of both the
      individual proteins and the nidogen-1/laminin gamma1 complex. This finding
      implies different modes of interaction resulting in several distinct protein
      protein interfaces. 

PMID- 25387008
TI  - Bacterial endophytic communities in the grapevine depend on pest management.
AB  - Microbial plant endophytes are receiving ever-increasing attention as a result of
      compelling evidence regarding functional interaction with the host plant.
      Microbial communities in plants were recently reported to be influenced by
      numerous environmental and anthropogenic factors, including soil and pest
      management. In this study we used automated ribosomal intergenic spacer analysis
      (ARISA) fingerprinting and pyrosequencing of 16S rDNA to assess the effect of
      organic production and integrated pest management (IPM) on bacterial endophytic
      communities in two widespread grapevines cultivars (Merlot and Chardonnay). High
      levels of the dominant Ralstonia, Burkholderia and Pseudomonas genera were
      detected in all the samples We found differences in the composition of endophytic
      communities in grapevines cultivated using organic production and IPM.
      Operational taxonomic units (OTUs) assigned to the Mesorhizobium, Caulobacter and
      Staphylococcus genera were relatively more abundant in plants from organic
      vineyards, while Ralstonia, Burkholderia and Stenotrophomonas were more abundant
      in grapevines from IPM vineyards. Minor differences in bacterial endophytic
      communities were also found in the grapevines of the two cultivars. 

PMID- 25387009
TI  - Ophthalmological features of Parkinson disease.
AB  - BACKGROUND: The aim of this study was to determine the type and frequency of
      ophthalmologic changes occurring in patients with Parkinson disease (PD).
      MATERIAL/METHODS: One hundred consecutive patients (196 eyes) with idiopathic PD
      and a control group consisting of 100 healthy patients (196 eyes) matched for age
      and sex underwent a complete ophthalmological examination of both eyes, including
      assessment of patient medical history, dry eye questionare, and visual
      hallucinations questionnaire, distance and near best corrected visual acuity
      (DBCVA, NBCVA), color vision, distance photopic contrast sensitivity, near point
      of convergence, slit lamp examination of the eye anterior segment, tear film
      osmolarity and breakup time, aqueous tear production, and intraocular pressure,
      as well as fundus examination and evaluation of the perimacular retinal thickness
      (RT) and peripapillary retinal nerve fiber layer (RNFL) thickness. RESULTS: In
      the eyes of PD patients DBCVA, NBCVA, contrast sensitivity, and color
      discrimination were significantly reduced. We also detected increased frequency
      of convergence insufficiency, seborrhoic blepharitis, meibomian gland disease
      (MGD), dry eye syndrome, nuclear and posterior subcapsular cataract, and glaucoma
      (p<0.05). However, intraocular pressure (IOP) was significantly lower in the PD
      group compared to controls. The frequency of visual hallucinations, age-related
      macular degeneration (ARMD), and other ophthalmological diseases, as well as RT
      and RNFL thickness, did not significantly differ between investigated groups.
      CONCLUSIONS: Clinicians need to be aware of the association between PD and
      ophthalmological changes. Restoration of good-quality vision has a great impact
      on PD patients' quality of life, reduction of costs of treatment and care, and
      rehabilitation.

PMID- 25387010
TI  - After 65 years, research is still fun.
AB  - In 1946, at the end of World War II, I entered graduate school at Cornell
      University, where I remained for 44 years. During that time, my laboratory
      produced more than 300 publications in the field of reproductive biology,
      including studies on nutrition and reproduction, the role of the hypothalamus in
      pituitary gonadotropin release, corpus luteum formation and function, hormone
      assays, and estrous cycle synchronization. At age seventy, I retired from Cornell
      and accepted the Gordon Cain Endowed Professorship at Louisiana State University,
      where I continued my work on the bovine corpus luteum and added research on the
      collection, maturation, in vitro fertilization, and culture of bovine oocytes. In
      1994, I moved to the Pennington Biomedical Research Center and soon thereafter
      started the research that led to development of the lytic peptide-gonadotropin
      conjugates, which target and destroy cancer cell membranes. I am continuing my
      work on the development of targeted cancer cell drugs and, yes, research is still
      fun! 

PMID- 25387012
TI  - Porcine circovirus type 2 (PCV2): pathogenesis and interaction with the immune
      system.
AB  - Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine
      circovirus-associated disease (PCVAD). The virus preferentially targets the
      lymphoid tissues, which leads to lymphoid depletion and immunosuppression in
      pigs. The disease is exacerbated by immunostimulation or concurrent infections
      with other pathogens. PCV2 resides in certain immune cells, such as macrophage
      and dendritic cells, and modulates their functions. Upregulation of IL-10 and
      proinflammatory cytokines in infected pigs may contribute to pathogenesis. Pig
      genetics influence host susceptibility to PCV2, but the viral genetic
      determinants for virulence remain unknown. PCV2 DNA and proteins interact with
      various cellular genes that control immune responses to regulate virus
      replication and pathogenesis. Both neutralizing antibodies and cell-mediated
      immunity are important immunological correlates of protection. Despite the
      availability of effective vaccines, variant strains of PCV2 continue to emerge.
      Although tremendous progress has been made toward understanding PCV2 pathogenesis
      and immune interactions, many important questions remain. 

PMID- 25387013
TI  - Comparative biology of gammadelta T cell function in humans, mice, and domestic
      animals.
AB  - gammadelta T cells are a functionally heterogeneous population and contribute to
      many early immune responses. The majority of their activity is described in
      humans and mice, but the immune systems of all jawed vertebrates include the
      gammadelta T cell lineage. Although some aspects of gammadelta T cells vary
      between species, critical roles in early immune responses are often conserved.
      Common features of gammadelta T cells include innate receptor expression, antigen
      presentation, cytotoxicity, and cytokine production. Herein we compare studies
      describing these conserved gammadelta T cell functions and other, potentially
      unique, functions. gammadelta T cells are well documented for their potential
      immunotherapeutic properties; however, these proposed therapies are often focused
      on human diseases and the mouse models thereof. This review consolidates some of
      these studies with those in other animals to provide a consensus for the current
      understanding of gammadelta T cell function across species. 

PMID- 25387014
TI  - Genetics of pigmentation in dogs and cats.
AB  - Color variation in companion animals has long been of interest to the breeding
      and scientific communities. Simple traits, like black versus brown or yellow
      versus black, have helped to explain principles of transmission genetics and
      continue to serve as models for studying gene action and interaction. We present
      a molecular genetic review of pigmentary variation in dogs and cats using a
      nomenclature and logical framework established by early leaders in the field. For
      most loci in which molecular variants have been identified (nine in dogs and
      seven in cats), homologous mutations exist in laboratory mice and/or humans.
      Exceptions include the K locus in dogs and the Tabby locus in cats, which give
      rise to alternating stripes or marks of different color, and which illustrate the
      continued potential of coat color genetics to provide insight into areas that
      transcend pigment cell biology. 

PMID- 25387011
TI  - Cross talk between animal and human influenza viruses.
AB  - Although outbreaks of highly pathogenic avian influenza in wild and domestic
      birds have been posing the threat of a new influenza pandemic for the past
      decade, the first pandemic of the twenty-first century came from swine viruses.
      This fact emphasizes the complexity of influenza viral ecology and the difficulty
      of predicting influenza viral dynamics. Complete control of influenza viruses
      seems impossible. However, we must minimize the impact of animal and human
      influenza outbreaks by learning lessons from past experiences and recognizing the
      current status. Here, we review the most recent influenza virology data in the
      veterinary field, including aspects of zoonotic agents and recent studies that
      assess the pandemic potential of H5N1 highly pathogenic avian influenza viruses. 

PMID- 25387015
TI  - Cats: a gold mine for ophthalmology.
AB  - Over 200 hereditary diseases have been identified and reported in the cat,
      several of which affect the eye, with homology to human hereditary disease.
      Compared with traditional murine models, the cat demonstrates more features in
      common with humans, including many anatomic and physiologic similarities, longer
      life span, increased size, and a genetically more heterogeneous background. The
      development of genomic resources in the cat has facilitated mapping and further
      characterization of feline models. During recent years, the wealth of knowledge
      in feline ophthalmology and neurophysiology has been extended to include new
      diseases of significant interest for comparative ophthalmology. This makes the
      cat an extremely valuable animal species to utilize for further research into
      disease processes affecting both cats and humans. This is especially true in the
      advancement and study of new treatment regimens and for extended therapeutic
      trials. Groups of feline eye diseases reviewed in the following are lysosomal
      storage disorders, congenital glaucoma, and neuroretinal degenerations. Each has
      important implications for human ophthalmic research. 

PMID- 25387016
TI  - Comparative aspects of mammary gland development and homeostasis.
AB  - Mammary glands are crucial to the reproductive strategy of mammals, and the milk
      of domesticated ruminants serves as an important source of nutrients for the
      human population. The majority of mammary gland development occurs postnatally,
      and the mammary gland undergoes cyclical periods of growth, differentiation,
      lactation, and regression that are coordinated to provide nutrients for offspring
      or are driven by strategies to manage reproduction and milk production of
      domesticated species. Growth and maintenance of the mammary epithelium depends on
      the function of mammary stem cells and progenitor cells. In this review, we
      provide an overview of postnatal mammary gland development, cyclical phases of
      mammary gland regression (regression during lactation and between successive
      lactations), and mammary stem cells and progenitor cells. Where possible, these
      processes are related to animal production and compared across species,
      particularly bovine, porcine, murine, and human. 

PMID- 25387018
TI  - Accelerating improvement of livestock with genomic selection.
AB  - Three recent breakthroughs have resulted in the current widespread use of DNA
      information: the genomic selection (GS) methodology, which is a form of marker
      assisted selection on a genome-wide scale, and the discovery of large numbers of
      single-nucleotide markers and cost effective methods to genotype them. GS
      estimates the effect of thousands of DNA markers simultaneously. Nonlinear
      estimation methods yield higher accuracy, especially for traits with major genes.
      The marker effects are estimated in a genotyped and phenotyped training
      population and are used for the estimation of breeding values of selection
      candidates by combining their genotypes with the estimated marker effects. The
      benefits of GS are greatest when selection is for traits that are not themselves
      recorded on the selection candidates before they can be selected. In the future,
      genome sequence data may replace SNP genotypes as markers. This could increase GS
      accuracy because the causative mutations should be included in the data. 

PMID- 25387019
TI  - Integrated genomic approaches to enhance genetic resistance in chickens.
AB  - The chicken has led the way among agricultural animal species in infectious
      disease control and, in particular, selection for genetic resistance. The
      generation of the chicken genome sequence and the availability of other
      empowering tools and resources greatly enhance the ability to select for enhanced
      disease resistance via genetic markers and to understand more deeply the
      biological basis of host resistance. In this review, we discuss how integrated
      genomic approaches are able to identify specific genes and genetic markers
      associated with disease resistance, give select examples of contemporary work
      involving various genomic strategies to identify disease resistance genes, and
      finish by giving some final thoughts on predicted applications in the near
      future. 

PMID- 25387017
TI  - Genetically engineered pig models for human diseases.
AB  - Although pigs are used widely as models of human disease, their utility as models
      has been enhanced by genetic engineering. Initially, transgenes were added
      randomly to the genome, but with the application of homologous recombination,
      zinc finger nucleases, and transcription activator-like effector nuclease (TALEN)
      technologies, now most any genetic change that can be envisioned can be
      completed. To date these genetic modifications have resulted in animals that have
      the potential to provide new insights into human diseases for which a good animal
      model did not exist previously. These new animal models should provide the
      preclinical data for treatments that are developed for diseases such as
      Alzheimer's disease, cystic fibrosis, retinitis pigmentosa, spinal muscular
      atrophy, diabetes, and organ failure. These new models will help to uncover
      aspects and treatments of these diseases that were otherwise unattainable. The
      focus of this review is to describe genetically engineered pigs that have
      resulted in models of human diseases. 

PMID- 25387020
TI  - Conservation genomics of threatened animal species.
AB  - The genomics era has opened up exciting possibilities in the field of
      conservation biology by enabling genomic analyses of threatened species that
      previously were limited to model organisms. Next-generation sequencing (NGS) and
      the collection of genome-wide data allow for more robust studies of the
      demographic history of populations and adaptive variation associated with fitness
      and local adaptation. Genomic analyses can also advance management efforts for
      threatened wild and captive populations by identifying loci contributing to
      inbreeding depression and disease susceptibility, and predicting fitness
      consequences of introgression. However, the development of genomic tools in wild
      species still carries multiple challenges, particularly those associated with
      computational and sampling constraints. This review provides an overview of the
      most significant applications of NGS and the implications and limitations of
      genomic studies in conservation. 

PMID- 25387021
TI  - Phytase, a new life for an "old" enzyme.
AB  - Phytases are phosphohydrolytic enzymes that initiate stepwise removal of
      phosphate from phytate. Simple-stomached species such as swine, poultry, and fish
      require extrinsic phytase to digest phytate, the major form of phosphorus in
      plant-based feeds. Consequently, this enzyme is supplemented in these species'
      diets to decrease their phosphorus excretion, and it has emerged as one of the
      most effective and lucrative feed additives. This chapter provides a
      comprehensive review of the evolving course of phytase science and technology. It
      gives realistic estimates of the versatile roles of phytase in animal feeding,
      environmental protection, rock phosphorus preservation, human nutrition and
      health, and industrial applications. It elaborates on new biotechnology and
      existing issues related to developing novel microbial phytases as well as phytase
      transgenic plants and animals. And it targets critical and integrated analyses on
      the global impact, novel application, and future demand of phytase in promoting
      animal agriculture, human health, and societal sustainability. 

PMID- 25387022
TI  - Effects of heat stress on postabsorptive metabolism and energetics.
AB  - Environmental-induced hyperthermia compromises efficient animal production and
      jeopardizes animal welfare. Reduced productive output during heat stress was
      traditionally thought to result from decreased nutrient intake. Our observations
      challenge this dogma and indicate that heat-stressed animals employ novel
      homeorhetic strategies to direct metabolic and fuel selection priorities
      independent of nutrient intake or energy balance. Alterations in systemic
      physiology support a shift in carbohydrate metabolism, evident through changes
      such as basal and stimulated circulating insulin levels. Hepatocyte and myocyte
      metabolism also show clear differences in glucose production and use during heat
      stress. Perhaps most intriguing, given the energetic shortfall of the heat
      stressed animal, is the apparent lack of fat mobilization from adipose tissue
      coupled with a reduced responsiveness to lipolytic stimuli. Thus, the heat stress
      response markedly alters postabsorptive carbohydrate, lipid, and protein
      metabolism independently of reduced feed intake through coordinated changes in
      fuel supply and utilization by multiple tissues. 

PMID- 25387023
TI  - Epigenetics: setting up lifetime production of beef cows by managing nutrition.
AB  - Longevity of cattle is correlated to reproductive success. Many studies in
      different species report the influence of maternal nutrition on progeny
      performance, health, and reproduction. Maternal nutrient status can cause
      epigenetic alterations to the genome of the developing fetus, which potentially
      can impact future generations. This review discusses fetal programming mechanisms
      as well as maternal nutrition's impact on placental development and progeny
      heifer performance and reproduction owing to nutrient restriction, age, or
      production status. Furthermore, we discuss how early neonatal nutrient intake and
      type can influence future productivity in the beef and dairy cow. Understanding
      how these factors influence progeny performance will enable cattlemen to produce
      replacement females better adapted to their environment through maternal nutrient
      regulation by stimulating fetal programming. 

PMID- 25387024
TI  - Systems physiology in dairy cattle: nutritional genomics and beyond.
AB  - Microarray development changed the way biologists approach the holistic study of
      cells and tissues. In dairy cattle biosciences, the application of omics
      technology, from spotted microarrays to next-generation sequencing and
      proteomics, has grown steadily during the past 10 years. Omics has found
      application in fields such as dairy cattle nutritional physiology, reproduction,
      and immunology. Generating biologically meaningful data from omics studies relies
      on bioinformatics tools. Both are key components of the systems physiology
      toolbox, which allows study of the interactions between a condition (e.g.,
      nutrition, physiological state) with tissue gene/protein expression and the
      associated changes in biological functions. The nature of physiologic and
      metabolic adaptations in dairy cattle at any stage of the life cycle is
      multifaceted, involves multiple tissues, and is dynamic, e.g., the transition
      from late-pregnancy to lactation. Application of integrative systems physiology
      in periparturient dairy cattle has already advanced knowledge of the simultaneous
      functional adaptations in liver, adipose, and mammary tissue. 

PMID- 25387025
TI  - In vivo and in vitro environmental effects on mammalian oocyte quality.
AB  - The oocyte is at the center of the equation that results in female fertility.
      Many factors influence oocyte quality, including external factors such as
      maternal nutrition, stress, and environmental exposures, as well as ovarian
      factors such as steroids, intercellular communication, antral follicle count, and
      follicular fluid composition. These influences are interconnected; changes in the
      external environment of the female translate into ovarian changes that affect the
      oocyte. The lengthy period during which the oocyte remains arrested in the ovary
      provides ample time and opportunity for environmental factors to take their toll.
      An appropriate environment for growth and maturation of the oocyte, in vivo and
      in vitro, is critical to ensure optimal oocyte quality, which determines the
      success of fertilization and preimplantation embryo development, and has long
      term implications for implantation, fetal growth, and offspring health. 

PMID- 25387027
TI  - The evolution of epitheliochorial placentation.
AB  - Epitheliochorial placentation is a derived condition and has evolved separately
      in strepsirrhine primates and laurasiatherians (pangolins, whales, and hoofed
      mammals). Usually it is associated with a long gestation period, small litters,
      and precocial young. Oxygen transfer is facilitated by indenting of the uterine
      and trophoblast epithelia by maternal and fetal capillaries, respectively.
      Histotrophic nutrition is important, and adaptations include areolas and
      hemophagous regions. In pigs and horses, for example, iron is transported as
      uteroferrin secreted from the uterine glands and taken up by areolas. In the
      horse, invasive trophoblast cells form cups within the endometrium that are the
      source of equine chorionic gonadotropin. In ruminants, binucleate trophoblast
      cells fuse with uterine epithelial cells to form trinucleate cells or plaques
      that secrete pregnancy hormones. There is evidence of immunosuppression in
      connection with these more invasive types of trophoblasts. The epitheliochorial
      condition may be advantageous for long pregnancies in large animals. 

PMID- 25387028
TI  - The role of productivity in improving the environmental sustainability of
      ruminant production systems.
AB  - The global livestock industry is charged with providing sufficient animal source
      foods to supply the global population while improving the environmental
      sustainability of animal production. Improved productivity within dairy and beef
      systems has demonstrably reduced resource use and greenhouse gas emissions per
      unit of food over the past century through the dilution of maintenance effect.
      Further environmental mitigation effects have been gained through the current use
      of technologies and practices that enhance milk yield or growth in ruminants;
      however, the social acceptability of continued intensification and use of
      productivity-enhancing technologies is subject to debate. As the environmental
      impact of food production continues to be a significant issue for all
      stakeholders within the field, further research is needed to ensure that
      comparisons among foods are made based on both environmental impact and nutritive
      value to truly assess the sustainability of ruminant products. 

PMID- 25387026
TI  - The equine endometrial cup reaction: a fetomaternal signal of significance.
AB  - A remarkable feature of equine pregnancy is the development of the invasive
      trophoblast of the chorionic girdle and its formation of the gonadotrophin
      secreting endometrial cup cells in early gestation. The details of this process
      have been revealed only slowly over the past century, since the first description
      of the endometrial cups in 1912. This centennial presents an opportunity to
      review the characteristics of the cells and molecules involved in this early,
      critical phase of placentation in the mare. The invasiveness of the chorionic
      girdle trophoblast appears to represent an atavistic attribute more commonly
      associated with the hemochorial placentae of primates and rodents but not with
      the more recently derived epitheliochorial placentae of the odd-toed ungulates.
      The nature of and raison d'etre for the strong fetal signals transmitted to the
      mare by the endometrial cup reaction, and her responses to these messages, are
      the subject of the present review. 

PMID- 25387029
TI  - Making slaughterhouses more humane for cattle, pigs, and sheep.
AB  - When a stunning method is being evaluated, it is essential that the animal
      handling and restraint methods that are used with it are also examined. This
      makes it possible to determine the effect of the entire system on animal welfare.
      Cattle, pigs, and sheep will move easily through the races at a slaughter plant
      if visual distractions such as reflections on shiny metal, dangling chains,
      moving equipment, or people up ahead are removed. The most important scientific
      research on captive bolt, CO2, and electrical stunning methods is reviewed. A
      common mistake made by people evaluating insensibility is to misinterpret
      reflexive leg kicks as a sign of return to sensibility. When religious slaughter
      is being evaluated, the variable of how the animal is restrained must be
      separated from the variable of slaughter without stunning. Slaughter can be done
      with a high level of animal welfare. 

PMID- 25387030
TI  - Solution processable MOF yellow phosphor with exceptionally high quantum
      efficiency.
AB  - An important aspect in the research and development of white light-emitting
      diodes (WLEDs) is the discovery of highly efficient phosphors free of rare-earth
      (RE) elements. Herein we report the design and synthesis of a new type of RE
      free, blue-excitable yellow phosphor, obtained by combining a strongly emissive
      molecular fluorophore with a bandgap modulating co-ligand, in a three-dimensional
      metal organic framework. [Zn6(btc)4(tppe)2(DMA)2] (btc = benzene-1,3,5
      tricarboxylate, tppe = 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethene, DMA =
      dimethylacetamide) crystallizes in a new structure type and emits bright yellow
      light when excited by a blue light source. It possesses the highest internal
      quantum yield among all RE-free, blue-excitable yellow phosphors reported to
      date, with a value as high as 90.7% (lambdaex = 400 nm). In addition to its high
      internal quantum yield, the new yellow phosphor also demonstrates high external
      quantum yield, luminescent and moisture stability, solution processability, and
      color tunability, making it a promising material for use in phosphor conversion
      WLEDs. 

PMID- 25387031
TI  - Validity of the Pediatric Running-Based Anaerobic Sprint Test to Determine
      Anaerobic Performance in Healthy Children.
AB  - PURPOSE: To determine criterion validity of the pediatric running-based anaerobic
      sprint test (RAST) as a nonsophisticated field test for evaluating anaerobic
      performance in healthy children and adolescents. METHODS: Data from 65 healthy
      children (28 boys and 37 girls between 6 and 18 years of age, mean +/- SD age:
      10.0 +/- 2.8 years) who completed both the pediatric RAST and the 30-s Wingate
      anaerobic test (WAnT) on a cycle ergometer in a randomized order were analyzed.
      Peak power (PP) and mean power (MP) were the primary outcome measures for both
      tests. RESULTS: There were no significant sex-differences in PP and MP attained
      at the pediatric RAST and the WAnT. Age was strongly correlated to pediatric RAST
      and WAnT performance (Spearman's rho values ranging from 0.85 to 0.90, with p <
      .001 for all coefficients). We found high correlation coefficients between
      pediatric RAST performance and WAnT performance for both PP (Spearman's rho:
      0.86; p < .001) and MP (Spearman's rho: 0.91; p < .001). CONCLUSION: The
      pediatric RAST can be used as a valid and nonsophisticated field test for the
      assessment of anaerobic performance in healthy children and adolescents. For
      clinical evaluative purposes, we suggest to use MP of the pediatric RAST when
      assessing glycolytic power in the absence of the WAnT.

PMID- 25387032
TI  - The effects of a protein osmolyte on the stability of the integral membrane
      protein glycerol facilitator.
AB  - Osmolytes are naturally occurring molecules used by a wide variety of organisms
      to stabilize proteins under extreme conditions of temperature, salinity,
      hydrostatic pressure, denaturant concentration, and desiccation. The effects of
      the osmolyte trimethylamine N-oxide (TMAO) as well as the influence of detergent
      head group and acyl chain length on the stability of the Escherichia coli
      integral membrane protein glycerol facilitator (GF) tetramer to thermal and
      chemical denaturation by sodium dodecyl sulphate (SDS) are reported. TMAO
      promotes the association of the normally tetrameric alpha-helical protein into
      higher order oligomers in dodecyl-maltoside (DDM), but not in tetradecyl
      maltoside (TDM), lyso-lauroylphosphatidyl choline (LLPC), or lyso
      myristoylphosphatidyl choline (LMPC), as determined by dynamic light scattering
      (DLS); an octameric complex is particularly stable as indicated by SDS
      polyacrylamide gel electrophoresis. TMAO increases the heat stability of the GF
      tetramer an average of 10  degrees C in the 4 detergents and also protects the
      protein from denaturation by SDS. However, it did not promote re-association to
      the tetramer when added to SDS-dissociated protein. TMAO also promotes the
      formation of rod-like detergent micelles, and DLS was found to be useful for
      monitoring the structure of the protein and the redistribution of detergent
      during thermal dissociation of the protein. The protein is more thermally stable
      in detergents with the phosphatidylcholine head group (LLPC and LMPC) than in the
      maltoside detergents. The implications of the results for osmolyte mechanism,
      membrane protein stability, and protein-protein interactions are discussed. 

PMID- 25387035
TI  - Collective ion diffusion and localized single particle dynamics in pyridinium
      based ionic liquids.
AB  - Quasielastic neutron scattering with polarized neutrons allows for an
      experimental separation of single-particle and collective processes, as contained
      in the incoherent and coherent scattering contributions. This technique was used
      to investigate the dynamical processes in the pyridinium-based ionic liquid 1
      butylpyridinium bis(trifluoromethylsulfonyl)-imide. We observed two diffusion
      processes with different time scales. The slower diffusional process was present
      in both the coherent and the incoherent contribution, meaning that this process
      has at least a partial collective nature. The second faster localized process is
      only present in the incoherent scattering contribution. We conclude that it is a
      true single-particle process on a shorter time scale. 

PMID- 25387036
TI  - Prevalence and determinants of pain in the ipsilateral upper limb of stroke
      patients.
AB  - This study investigated the prevalence of pain in the ipsilateral upper-limb in
      stroke patients. 229 stroke patients (133 men, 96 women; M age = 59.0 yr., SD =
      12.4) were assessed with the Pain Behaviors Scales and their motor weakness was
      measured with the Motricity Index. Results indicated that over 27% of patients
      experienced pain in at least one joint of the ipsilateral upper limb. Shoulder
      pain was the most common. Further analysis indicated that the occurrence of pain
      in the ipsilateral upper limb was higher among women, among patients who used a
      cane, and among patients with a greater weakness of the affected lower limb.

PMID- 25387037
TI  - Children's construction task performance and spatial ability: controlling task
      complexity and predicting mathematics performance.
AB  - This paper presents a methodology to control construction task complexity and
      examined the relationships between construction performance and spatial and
      mathematical abilities in children. The study included three groups of children
      (N = 96); ages 7-8, 10-11, and 13-14 years. Each group constructed seven pre
      specified objects. The study replicated and extended previous findings that
      indicated that the extent of component symmetry and variety, and the number of
      components for each object and available for selection, significantly predicted
      construction task difficulty. Results showed that this methodology is a valid and
      reliable technique for assessing and predicting construction play task
      difficulty. Furthermore, construction play performance predicted mathematical
      attainment independently of spatial ability.

PMID- 25387038
TI  - Psychological predictors of mental toughness in elite tennis: an exploratory
      study in learned resourcefulness and competitive trait anxiety.
AB  - The purpose of this study was to examine the extent to which two constructs,
      learned resourcefulness and competitive trait anxiety, measured by the Self
      Control Schedule and Sports Competition Anxiety Test, respectively, predicted
      mental toughness on the Sports Mental Toughness Questionnaire among male and
      female elite tennis players. The participants included two NCAA Division 1 (U.S.)
      intercollegiate tennis teams comprising eight male (M age = 19.4 yr., SD = 1.2)
      and eight female (M age = 20.9 yr., SD = 1.4) players and their respective head
      coaches (N = 2, M age = 28 yr., SD = 5.7). Results of regression analyses
      indicated that learned resourcefulness was the primary predictor of athlete self
      rated mental toughness and that competitive trait anxiety was relatively
      unrelated to coach and athlete-rated mental toughness. The positive significant
      relationship between mental toughness and learned resourcefulness suggests that
      the latter may be an integral component of mental toughness, at least among elite
      tennis players. Further research is needed to examine related components of
      mental toughness, including learned resourcefulness, and to determine the
      effectiveness of interventions that increase mental toughness to optimal levels,
      particularly as a function of sport type.

PMID- 25387039
TI  - Development of the color scale of perceived exertion: preliminary validation.
AB  - This study developed a Color Scale of Perceived Exertion (RPE-color scale) and
      assessed its concurrent and construct validity in adult women. One hundred
      participants (18-77 years), who were habitual exercisers, associated colors with
      verbal anchors of the Borg RPE scale (RPE-Borg scale) for RPE-color scale
      development. For RPE-color scale validation, 12 Young (M = 21.7 yr., SD = 1.5)
      and 10 Older (M = 60.3 yr., SD = 3.5) adult women performed a maximal graded
      exercise test on a treadmill and reported perceived exertion in both RPE-color
      and RPE-Borg scales. In the Young group, the RPE-color scale was significantly
      associated with heart rate and oxygen consumption, having strong correlations
      with the RPE-Borg scale. In the Older group, the RPE-color scale was
      significantly associated with heart rate, having moderate to high correlations
      with the RPE-Borg scale. The RPE-color scale demonstrated concurrent and
      construct validity in the Young women, as well as construct validity in Older
      adults.

PMID- 25387040
TI  - Analysis of physical activity and acculturation among Turkish migrants in Germany
      and England (.).
AB  - Recent literature shows that migrant populations in Western countries are
      generally less physically active than their host populations. The purpose of the
      present study was to expand research investigating associations between physical
      activity (PA) and acculturation and their relationship with several socio
      demographic factors among Turkish migrants in Germany and England. The sample
      consisted of 521 Turkish migrants. Migrant generation, length of residence, and
      language proficiency were used as indicators of acculturation. Acculturation was
      not associated with PA among migrants in Germany and England. PA of migrants was
      significantly associated with migrant's host country, age, sex, marital status,
      and education. The total PA of migrants in Germany was higher than that of
      migrants in England; the large majority of females in both Germany and England
      had low PA, whereas most males had moderate PA. Seemingly, PA in Turkish migrant
      populations will not necessarily increase as a result of greater acculturation to
      the host society.

PMID- 25387041
TI  - Effects of inference demands and structural complexity on transitive inference
      processing: comment on Lee and Kwon (2013) (.).
AB  - In a recent study that investigated the processing of transitive inferences, Lee
      and Kwon (2013 ) concluded that only informational complexity leads to processing
      difficulty, that structural complexity affects earlier stages of processing than
      informational complexity, and that working memory resources are shared between
      sentence processing and other cognitive processes. Here, the evidence for these
      findings is scrutinized, and it is argued that there exist significant
      difficulties in drawing such conclusions based on the methodology and presented
      data.

PMID- 25387042
TI  - Exploring General and Sports Nutrition and Food Knowledge in Elite Male
      Australian Athletes.
AB  - Nutrition knowledge is believed to influence nutritional intake, which in turn
      influences performance in elite athletes. There is currently no published data on
      the nutrition knowledge of elite Australian Football (AF) players. The purpose of
      this study was to gain insight into the current level of general and sports
      nutrition knowledge in elite male AF athletes. Forty six elite male AF players
      (23.5 +/- 2.8 years) answered 123 questions relating to five areas of nutrition
      knowledge: dietary recommendations, sources of nutrients, choosing everyday
      foods, alcohol and sports nutrition. Demographic details and perceptions of
      nutrition knowledge were collected for all participants. The mean nutrition
      knowledge score was 74.4 +/- 10.9 (60.5%). The highest score was obtained in
      sports nutrition section (17.9 +/- 3.0, 61.7%). The dietitian was selected as the
      first source of information by 98% of athletes, with club trainer and teammates
      as second choice for 45.7% and 23.9% of athletes, respectively. The majority of
      athletes correctly answered questions regarding recommendations to increase fruit
      and vegetable intake and decrease fat intake (95.6%, 91.1% and 93.3% correct
      respectively). While 80% of the athletes were aware fat intake should
      predominately be made up of unsaturated fat, they were less able to identify food
      sources of unsaturated fats (35.6% and 24.4% correct for statements regarding
      monounsaturated and polyunsaturated fats, respectively). Broad nutrition messages
      and recommendations appear to be well understood; however, gaps in nutrition
      knowledge are evident. A better understanding of nutrition knowledge in athletes
      will allow nutrition education interventions to target areas in need of
      improvement. 

PMID- 25387043
TI  - Polymerization topochemistry of cellulose nanocrystals: a function of surface
      dehydration control.
AB  - The activation (dehydration) of cellulose nanocrystals (CNCs) toward surface
      "brush" polymerization is accomplished either by freeze drying or solvent
      exchange. However, the question of which one of these protocols to choose over
      the other is generally open-ended. The current study attempts to shed light on
      this question by installing a standard polymer, polycaprolactone (PCL), onto the
      surface of both freeze-dried and solvent-exchanged CNCs by ring-opening
      polymerization (ROP) and examining the differences in polymerization and final
      product properties. The work is the first to demonstrate that the efficiency of
      surface polymerization and final product properties are in fact influenced by the
      protocols. The differences between the two sample PCL-grafted CNCs were
      investigated by X-ray photoelectron spectroscopy (XPS), elemental analysis, gel
      permeation chromatography (GPC), and contact-angle measurements. The freeze-dried
      samples had a significantly reduced PCL surface density. The crystallinity of the
      solvent-exchanged PCL-grafted CNCs (SECNC-g-PCL), however, was lower than that of
      either pure CNCs or freeze-dried PCL-grafted CNCs (FDCNC-g-PCL). It was
      determined that solvent exchange sufficiently modified the CNC surface to provide
      enhanced reactivity, an effect that was not as apparent for FDCNC-g-PCL. The
      solvent-exchanged CNCs tended to have more porous, nanotextured surfaces that
      were tended to be more responsive toward brush polymerization. In addition to the
      physical dissimilarities in surface morphology and surface accessibility
      contributing to topochemical differences between the two species, it was also
      found that the dispersibility, aggregation, and thermal stability were different.

PMID- 25387044
TI  - Healing pathways: longitudinal effects of religious coping and social support on
      PTSD symptoms in African American sexual assault survivors.
AB  - African American women are at a slightly increased risk for sexual assault (A.
      Abbey, A. Jacques-Tiaura, & M. Parkhill, 2010). However, because of stigma,
      experiences of racism, and historical oppression, African American women are less
      likely to seek help from formal agencies compared to White women (Lewis et al.,
      2005; S. E. Ullman & H. H. Filipas, 2001) and/or women of other ethnic
      backgrounds (C. Ahrens, S. Abeling, S. Ahmad, & J. Himman, 2010). Therefore, the
      provision of culturally appropriate services, such as the inclusion of religion
      and spiritual coping, may be necessary when working with African American women
      survivors of sexual assault. Controlling for age and education, the current study
      explores the impact of religious coping and social support over 1 year for 252
      African American adult female sexual assault survivors recruited from the Chicago
      metropolitan area. Results from hierarchical linear regression analyses reveal
      that high endorsement of religious coping and social support at Time 1 does not
      predict a reduction in posttraumatic stress disorder (PTSD) symptoms at Time 2.
      However, high social support at Time 2 does predict lower PTSD at Time 2. Also,
      it is significant to note that survivors with high PTSD at Time 1 and Time 2
      endorse greater use of social support and religious coping. Clinical and research
      implications are explored. 

PMID- 25387045
TI  - Oxidative uncoupling in cysteine dioxygenase is gated by a proton-sensitive
      intermediate.
AB  - Cysteine dioxygenase (CDO) is a non-heme mononuclear iron enzyme that catalyzes
      the O2-dependent oxidation of l-cysteine (Cys) to produce cysteine sulfinic acid
      (CSA). This enzyme catalyzes the first committed step in Cys catabolism; thus, it
      is central to mammalian sulfur metabolism and redox homeostasis. Ironically,
      despite nearly 45 years of continued research on CDO, essentially no information
      has been reported with respect to its kinetic mechanism. In this work, the timing
      of chemical steps in the CDO kinetic mechanism is investigated by pH/pD-dependent
      steady-state kinetics and solvent isotope effects on kcat, kcat/KM, and (O2/CSA)
      coupling. Normal solvent kinetic isotope effects of 1.45 +/- 0.05 and 2.0 +/- 0.1
      are observed in kcat-pL and kcat/KM-pL profiles, respectively. Proton inventory
      experiments within the pL-independent region (pL 8.5) suggest multiple solvent
      exchangeable protons in flight for both kcat and kcat/KM data. The influence of
      solvent viscosity was also investigated to probe non-chemical steps and to verify
      that the apparent isotope effects were not attributable to increased solvent
      viscosity of D2O reactions relative to H2O. Although solvent viscosity did have a
      modest influence on kcat and kcat/KM, the response is not sufficient to account
      for the observed solvent isotope effects. This suggests that product release is
      only partially rate-limiting for CDO catalysis. Most crucially, proton inventory
      of (O2/CSA) coupling indicates that a proton-sensitive transition state directly
      follows O2 activation. Thus, protonation of a transient species preceding Cys
      oxidation is gated by protons in flight. This behavior provides valuable insight
      into the kinetically masked transients generated during catalysis. 

PMID- 25387046
TI  - Diagnostic and Therapeutic Challenges.

PMID- 25387047
TI  - Geographic atrophy in patients receiving anti-vascular endothelial growth factor
      for neovascular age-related macular degeneration.
AB  - PURPOSE: To examine factors associated with the apparent growth of geographic
      atrophy (GA) in a consecutive series of eyes with treatment-naive neovascular age
      related macular degeneration receiving intravitreal anti-vascular endothelial
      growth factor therapy on a treat-and-extend regimen. METHODS: This was a
      retrospective cohort study. Two independent graders identified areas of GA using
      near-infrared reflectance imaging and spectral domain optical coherence
      tomography (SD-OCT). Neovascular lesion subtypes were classified based on
      fluorescein angiography (FA) as occult choroidal neovascularization, classic
      choroidal neovascularization, retinal angiomatous proliferation, or mixed
      choroidal neovascularization, and by the anatomical classification system which
      utilizes FA and SD-OCT as Types 1 (sub-retinal pigment epithelium), 2
      (subretinal), 3 (intraretinal), or mixed neovascularization. RESULTS: Ninety-one
      patients (94 eyes) fit the inclusion criteria, of which 52 eyes (55.3%)
      experienced apparent GA growth. The odds of developing apparent GA were
      significantly lower in Type 1 neovascularization compared to the other lesion
      types (P < 0.001). Using both FA and SD-OCT to classify neovascular age-related
      macular degeneration significantly improves the goodness of fit in the
      correlation between apparent GA growth and baseline neovascular lesion type (P <
      0.001). CONCLUSION: Treatment-naive neovascular age-related macular degeneration
      eyes with Type 1 neovascularization at baseline were less likely to develop GA
      than eyes with other types. The correlation between apparent GA growth and
      subtype of neovascularization is stronger when lesions are classified with an
      anatomic grading that utilizes both FA and SD-OCT.

PMID- 25387048
TI  - Multimodal imaging of white and dark without pressure fundus lesions.
AB  - PURPOSE: To describe multimodal imaging findings in patients with dark or white
      without pressure lesions of the fundus. METHODS: Retrospective observational case
      series of 10 patients with white or dark without pressure lesions. We analyzed
      multimodal imaging using spectral domain optical coherence tomography, color and
      near-infrared fundus photography, and fundus autofluorescence imaging to explore
      the findings associated with these lesions. RESULTS: All patients had geographic
      dark or white lesions on clinical examination and color photography, which were
      either hyporeflective or hyperreflective on near-infrared reflectance imaging,
      respectively. On optical coherence tomography, these lesions correlated with an
      abrupt change of the photoreceptor reflectivity, with relative hyporeflectivity
      of photoreceptor zones (ellipsoid and interdigitation zones, as well as outer
      segments) within the dark, and relative hyperreflectivity within white lesions.
      Ten patients underwent fundus autofluorescence, which showed well-defined zones
      of relative hypo-autofluorescence within the lesion, compared with neighboring
      uninvolved regions, whether dark or white without pressure. In two patients who
      had a lesion combining white and dark without pressure, we observed the
      transition in photoreceptor reflectivity from the dark lesion (hyporeflective) to
      the white lesion (hyperreflective), relative to the surrounding retina.
      CONCLUSION: Both white and dark without pressure lesions are associated with
      changes in outer retinal reflectivity on optical coherence tomography, which
      occur in opposite directions compared with the surrounding unaffected areas. In
      the face of normal visual field testing to date, the clinical significance of
      this finding remains uncertain. Recognition of the optical coherence tomography
      appearance will help clinicians avoid unnecessary workup of these patients for
      outer retinal dystrophy or degeneration.

PMID- 25387049
TI  - Correspondence.

PMID- 25387050
TI  - Subtype differentiation of renal tumors using voxel-based histogram analysis of
      intravoxel incoherent motion parameters.
AB  - OBJECTIVES: The aim of this study was to determine if voxel-based histogram
      analysis of intravoxel incoherent motion imaging (IVIM) parameters can
      differentiate various subtypes of renal tumors, including benign and malignant
      lesions. SUBJECTS AND METHODS: A total of 44 patients with renal tumors who
      underwent surgery and had histopathology available were included in this Health
      Insurance Portability and Accountability Act-compliant, institutional review
      board-approved, single-institution prospective study. In addition to routine
      renal magnetic resonance imaging examination performed on a 1.5-T system, all
      patients were imaged with axial diffusion-weighted imaging using 8 b values
      (range, 0-800 s/mm). A biexponential model was fitted to the diffusion signal
      data using a segmented algorithm to extract the IVIM parameters perfusion
      fraction (fp), tissue diffusivity (Dt), and pseudodiffusivity (Dp) for each
      voxel. Mean and histogram measures of heterogeneity (standard deviation,
      skewness, and kurtosis) of IVIM parameters were correlated with pathology results
      of tumor subtype using unequal variance t tests to compare subtypes in terms of
      each measure. Correction for multiple comparisons was accomplished using the
      Tukey honestly significant difference procedure. RESULTS: A total of 44 renal
      tumors including 23 clear cell (ccRCC), 4 papillary (pRCC), 5 chromophobe, and 5
      cystic renal cell carcinomas, as well as benign lesions, 4 oncocytomas (Onc) and
      3 angiomyolipomas (AMLs), were included in our analysis. Mean IVIM parameters fp
      and Dt differentiated 8 of 15 pairs of renal tumors. Histogram analysis of IVIM
      parameters differentiated 9 of 15 subtype pairs. One subtype pair (ccRCC vs pRCC)
      was differentiated by mean analysis but not by histogram analysis. However, 2
      other subtype pairs (AML vs Onc and ccRCC vs Onc) were differentiated by
      histogram distribution parameters exclusively. The standard deviation of Dt
      [sigma(Dt)] differentiated ccRCC (0.362 +/- 0.136 * 10 mm/s) from AML (0.199 +/-
      0.043 * 10 mm/s) (P = 0.002). Kurtosis of fp separated Onc (2.767 +/- 1.299) from
      AML (-0.325 +/- 0.279; P = 0.001), ccRCC (0.612 +/- 1.139; P = 0.042), and pRCC
      (0.308 +/- 0.730; P = 0.025). CONCLUSIONS: Intravoxel incoherent motion imaging
      parameters with inclusion of histogram measures of heterogeneity can help
      differentiate malignant from benign lesions as well as various subtypes of renal
      cancers.

PMID- 25387051
TI  - Sulfur incorporation: copper-catalyzed cascade cyclization of 1,7-enynes with
      metal sulfides toward thieno[3,4-c]quinolin-4(5H)-ones.
AB  - A novel copper-catalyzed cascade cyclization of 1,7-enynes with metal sulfides is
      described. This sulfur-incorporation method provides straightforward access
      toward the important thiophene-fused quinolin-4(5H)-one scaffold through
      cyclization and double C-S bond formation cascade, and the chemoselectivity of
      this 1,7-enyne cyclization toward 1,3,3a,9b-tetrahydrothieno[3,4-c]quinolin-4(5H)
      ones and 3,3a-dihydrothieno[3,4-c]quinolin-4(5H)-ones can be controlled by
      varying the sulfur resources. 

PMID- 25387053
TI  - Hepatitis C virus-associated cancer.
AB  - Hepatitis C virus (HCV) is one of the major etiologic agents of liver cancer. HCV
      is an RNA virus that, unlike hepatitis B virus, is unable to integrate into the
      host genome. Through complex interactions between viral and host proteins that
      induce host responses and promote inflammation, fibrosis, and ultimately
      cirrhosis, HCV infection can result in the development of hepatocellular
      carcinoma (HCC). The HCV oncogenic process involves genetic and epigenetic
      alterations and oncogenic effects mediated by viral proteins in the activation of
      cellular oncogenes, inactivation of tumor-suppressor genes, and dysregulation of
      multiple signal-transduction pathways. Advances in genetics and gene expression
      profiling have enhanced our current understanding of the pathways involved in HCV
      associated liver cancer development. In this review, we summarize the current
      understanding of mechanisms of hepatocarcinogenesis induced by HCV infection. 

PMID- 25387052
TI  - Increasing beta-cell mass requires additional stimulation for adaptation to
      secretory demand.
AB  - Type 2 diabetes mellitus (T2DM) is caused by relative insulin deficiency,
      subsequent to both reduced beta-cell mass and insufficient insulin secretion, and
      both augmenting beta-cell mass and beta-cell function are therapeutic strategies
      for treating T2DM. However, the relative significance of increasing beta-cell
      mass vs improving beta-cell stimulus secretion coupling remains unclear. We have
      developed a mouse model that allows proliferation of beta-cells in adult mice
      without affecting beta-cell function by inducible expression of the positive cell
      cycle regulator cyclin A2 specifically in beta-cells. In these mice, when kept on
      a standard diet, doubling of beta-cell mass does not result in altered glucose
      tolerance or glucose-stimulated circulating insulin levels. Notably, a doubling
      of beta-cell mass also does not confer improved glycemic control and ability of
      beta-cells to respond to diabetogenic high-fat diet-induced glucose intolerance.
      However, in high-fat diet-exposed mice, an increase in endogenous beta-cell mass
      confers increased potentiation of in vivo glucose-stimulated rise in circulating
      insulin in response to acute pharmacologic treatment with the incretin glucagon
      like peptide-1 receptor agonist exendin-4. These observations indicate that
      increasing endogenous beta-cell mass may not be sufficient to improve glycemic
      control in T2DM without additional strategies to increase beta-cell stimulus
      secretion coupling. 

PMID- 25387054
TI  - AA amyloidosis: pathogenesis and targeted therapy.
AB  - The understanding of why and how proteins misfold and aggregate into amyloid
      fibrils has increased considerably during recent years. Central to amyloid
      formation is an increase in the frequency of the beta-sheet structure, leading to
      hydrogen bonding between misfolded monomers and creating a fibril that is
      comparably resistant to degradation. Generation of amyloid fibrils is nucleation
      dependent, and once formed, fibrils recruit and catalyze the conversion of native
      molecules. In AA amyloidosis, the expression of cytokines, particularly
      interleukin 6, leads to overproduction of serum amyloid A (SAA) by the liver. A
      chronically high plasma concentration of SAA results in the aggregation of
      amyloid into cross-beta-sheet fibrillar deposits by mechanisms not fully
      understood. Therefore, AA amyloidosis can be thought of as a consequence of long
      standing inflammatory disease. This review summarizes current knowledge about AA
      amyloidosis. The systemic amyloidoses have been regarded as intractable
      conditions, but improvements in the understanding of fibril composition and
      pathogenesis over the past decade have led to the development of a number of
      different therapeutic approaches with promising results. 

PMID- 25387055
TI  - Emerging concepts in Alzheimer's disease.
AB  - Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) is the most
      common neuropathologic substrate of dementia. It is characterized by synapse loss
      (predominantly within neocortex) as well as deposition of certain distinctive
      lesions (the result of protein misfolding) throughout the brain. The latter
      include senile plaques, composed mainly of an amyloid (Abeta) core and a neuritic
      component; neurofibrillary tangles, composed predominantly of hyperphosphorylated
      tau; and cerebral amyloid angiopathy, a microangiopathy affecting both cerebral
      cortical capillaries and arterioles and resulting from Abeta deposition within
      their walls or (in the case of capillaries) immediately adjacent brain
      parenchyma. In this article, I discuss the hypothesized role these lesions play
      in causing cerebral dysfunction, as well as CSF and neuroimaging biomarkers (for
      dementia) that are especially relevant as immunotherapeutic approaches are being
      developed to remove Abeta from the brain parenchyma. In addition, I address the
      role of neuropathology in characterizing the sequelae of new AD/SDAT therapies
      and helping to validate CSF and neuroimaging biomarkers of disease. Comorbidity
      of AD/SDAT and various types of cerebrovascular disease is a major theme in
      dementia research, especially as cognitive impairment develops in the oldest old,
      who are especially vulnerable to ischemic and hemorrhagic brain lesions. 

PMID- 25387056
TI  - A clearer view of the molecular complexity of clear cell renal cell carcinoma.
AB  - The von Hippel-Lindau (VHL) tumor suppressor gene is mutated as an early event in
      almost all cases of clear cell renal cell carcinoma (ccRCC), the most frequent
      form of kidney cancer. In this review we discuss recent advances in understanding
      how dysregulation of the many hypoxia-inducible factor alpha-dependent and 
      independent functions of the VHL tumor suppressor protein (pVHL) can contribute
      to tumor initiation and progression. Recent evidence showing extensive inter- and
      intratumoral genetic diversity has given rise to the idea that ccRCC should
      actually be considered as a series of molecularly related, yet distinct, diseases
      defined by the pattern of combinatorial genetic alterations present within the
      cells of the tumor. We highlight the range of genetic and epigenetic alterations
      that recur in ccRCC and discuss the mechanisms through which these events appear
      to function cooperatively with a loss of pVHL function in tumorigenesis. 

PMID- 25387058
TI  - SWI/SNF chromatin remodeling and human malignancies.
AB  - The SWI/SNF complexes, initially identified in yeast 20 years ago, are a family
      of multi-subunit complexes that use the energy of adenosine triphosphate (ATP)
      hydrolysis to remodel nucleosomes. Chromatin remodeling processes mediated by the
      SWI/SNF complexes are critical to the modulation of gene expression across a
      variety of cellular processes, including stemness, differentiation, and
      proliferation. The first evidence of the involvement of these complexes in
      carcinogenesis was provided by the identification of biallelic, truncating
      mutations of the SMARCB1 gene in malignant rhabdoid tumors, a highly aggressive
      childhood cancer. Subsequently, genome-wide sequencing technologies have
      identified mutations in genes encoding different subunits of the SWI/SNF
      complexes in a large number of tumors. SWI/SNF mutations, and the subsequent
      abnormal function of SWI/SNF complexes, are among the most frequent gene
      alterations in cancer. The mechanisms by which perturbation of the SWI/SNF
      complexes promote oncogenesis are not fully elucidated; however, alterations of
      SWI/SNF genes obviously play a major part in cancer development, progression,
      and/or resistance to therapy. 

PMID- 25387059
TI  - Leukocyte chemoattractant receptors in human disease pathogenesis.
AB  - Combinations of leukocyte attractant ligands and cognate heptahelical receptors
      specify the systemic recruitment of circulating cells by triggering integrin
      dependent adhesion to endothelial cells, supporting extravasation, and directing
      specific intratissue localization via gradient-driven chemotaxis. Chemoattractant
      receptors also control leukocyte egress from lymphoid organs and peripheral
      tissues. In this article, we summarize the fundamental mechanics of leukocyte
      trafficking, from the evolution of multistep models of leukocyte recruitment and
      navigation to the regulation of chemoattractant availability and function by
      atypical heptahelical receptors. To provide a more complete picture of the
      migratory circuits involved in leukocyte trafficking, we integrate a number of
      nonchemokine chemoattractant receptors into our discussion. Leukocyte
      chemoattractant receptors play key roles in the pathogenesis of autoimmune
      diseases, allergy, inflammatory disorders, and cancer. We review recent advances
      in our understanding of chemoattractant receptors in disease pathogenesis, with a
      focus on genome-wide association studies in humans and the translational
      implications of mechanistic studies in animal disease models. 

PMID- 25387057
TI  - The role of endoplasmic reticulum stress in human pathology.
AB  - Numerous genetic and environmental insults impede the ability of cells to
      properly fold and posttranslationally modify secretory and transmembrane proteins
      in the endoplasmic reticulum (ER), leading to a buildup of misfolded proteins in
      this organelle--a condition called ER stress. ER-stressed cells must rapidly
      restore protein-folding capacity to match protein-folding demand if they are to
      survive. In the presence of high levels of misfolded proteins in the ER, an
      intracellular signaling pathway called the unfolded protein response (UPR)
      induces a set of transcriptional and translational events that restore ER
      homeostasis. However, if ER stress persists chronically at high levels, a
      terminal UPR program ensures that cells commit to self-destruction. Chronic ER
      stress and defects in UPR signaling are emerging as key contributors to a growing
      list of human diseases, including diabetes, neurodegeneration, and cancer. Hence,
      there is much interest in targeting components of the UPR as a therapeutic
      strategy to combat these ER stress-associated pathologies.

PMID- 25387060
TI  - Spectroscopic study on uranyl carboxylate complexes formed at the surface layer
      of Sulfolobus acidocaldarius.
AB  - The complexation of U(vi) at the proteinaceous surface layer (S-layer) of the
      archaeal strain Sulfolobus acidocaldarius was investigated over a pH range from
      pH 1.5 to 6 at the molecular scale using time-resolved laser-induced fluorescence
      spectroscopy (TRLFS) and U L(III)-edge extended X-ray absorption fine structure
      (EXAFS). The S-layer, which represents the interface between the cell and its
      environment, is very stable against high temperatures, proteases, and detergents.
      This allowed the isolation and purification of S-layer ghosts (= empty cells)
      that maintain the size and shape of the cells. In contrast to many other
      microbial cell envelope compounds the studied S-layer is not phosphorylated,
      enabling the investigation of uranyl carboxylate complexes formed at microbial
      surfaces. The latter are usually masked by preferentially formed uranyl phosphate
      complexes. We demonstrated that at highly acidic conditions (pH 1.5 to 3) no
      uranium was bound by the S-layer. In contrast to that, at moderate acidic pH
      conditions (pH 4.5 and 6) a complexation of U(vi) at the S-layer via deprotonated
      carboxylic groups was stimulated. Titration studies revealed dissociation
      constants for the carboxylic groups of glutamic and aspartic acid residues of
      pK(a) = 4.78 and 6.31. The uranyl carboxylate complexes formed at the S-layer did
      not show luminescence properties at room temperature, but only under cryogenic
      conditions. The obtained luminescence maxima are similar to those of uranyl
      acetate. EXAFS spectroscopy demonstrated that U(vi) in these complexes is mainly
      coordinated to carboxylate groups in a bidentate binding mode. The elucidation of
      the molecular structure of these complexes was facilitated by the absence of
      phosphate groups in the studied S-layer protein.

PMID- 25387061
TI  - Kimura's disease involving the peripheral nerve of the arm in a child: a case
      report.
AB  - A 7-year-old Korean boy was referred for a nontender mass in the left arm. He had
      a 5-year history of a poorly defined painless mass on the medial side of the left
      elbow. The ultrasonogram of the left arm indicated an ill-defined, lobulating
      solid mass involving the deep soft tissue layer. The fat-suppressed T2-weighted
      magnetic resonance image showed a poorly marginated, homogeneous high-signal
      intensity mass. On further follow-up of 1 year and 6 months, the mass showed no
      change in size and nature. At surgery, a poorly demarcated inflammatory mass was
      dissected from a branch of the superficial radial nerve and excised completely.
      There was no recurrence and any dysfunction, except temporary localized
      hypoesthesia of the medial aspect of the left arm at the 3.6-year follow-up. 

PMID- 25387062
TI  - The preliminary outcome of syndactyly management in children with a new external
      separation device.
AB  - To introduce a new external fixation device for the management of syndactyly in
      children. To evaluate its preliminary clinical result. From January 2011 to June
      2012, 12 cases with cutaneous syndactyly of the middle/ring finger were managed
      with a new external fixator designed by our department. There were eight cases on
      the right side and four on the left side. The web space and soft tissue were
      stretched gradually using the new device. A Z-plasty of syndactylies was
      performed when the web space has reached the width that we required. The results
      were evaluated according to the clinical appearance and function of the fingers.
      Twelve cases had been followed up, with an average time of 16 months (range, 12
      27 months). The web space and soft tissue in all the cases were stretched
      successfully using the new device. Skin grafting was not necessary in the
      reconstruction of syndactyly. In the last follow-up, the Vancouver Score averaged
      0.6 (range, 0-2). Three cases had grade 1 web creep, whereas the other nine cases
      had grade 0 web creep. The total active motion averaged 130.4 degrees  for all
      affected fingers: 130.8 degrees  for the middle and 130.0 degrees  for the ring
      finger. Stiffness in the PIP joint preoperatively in two cases did not improve
      postoperatively. In 12 affected middle fingers, three cases had a supination
      deformity averaging 10.6 degrees  (range, 5 degrees -15 degrees ) and one case
      had a pronation deformity of 5 degrees . In 12 affected ring fingers, one case
      had a supination deformity of 18 degrees  and two cases had a pronation deformity
      averaging 7.5 degrees  (range, 5 degrees -10 degrees ). The middle finger was not
      pronated in any patient. Among all the ring fingers, two had radial deviation of
      8 degrees and 25 degrees  and 1 had ulnar deviation of 10 degrees . The surgeon
      provided visual analog scale score for esthetics averaged 1.8 (range, 0-5). The
      parent-provided visual analog scale score was 2.7 (range, 1-5) for pain, 1.3
      (range, 0-5) for appearance, and 1.3 (range, 0-5) for function. Displacement of
      the nail bed during distraction was found in two cases, which was resolved by the
      Winograd technique in the second surgery of syndactyly release. The clinical
      appearance and function were excellent. When we use the new external fixation
      device in the management of syndactyly, we can achieve a satisfactory outcome
      with little scar of the fingers. There was no need for skin grafting. However,
      the long-term result should be studied further. 

PMID- 25387063
TI  - Effect of topography on the wetting of nanoscale patterns: experimental and
      modeling studies.
AB  - We investigated the influence of nanoscale pattern shapes, contours, and surface
      chemistry on wetting behavior using a combination of experimental and modeling
      approaches. Among the investigated topographical shapes, re-entrant geometries
      showed superior performance owing to their ability to restrain the liquid-air
      interface in accordance with Gibbs criteria. The wetting state is also controlled
      by the surface texture in addition to the surface chemistry. Topographies with
      smaller intrinsic angles are better able to support the liquid droplet. Based on
      these observations, two geometrical relationships for designing superhydrophobic
      patterns exhibiting the Cassie-Baxter state are proposed. A detailed analysis of
      the simulation results showed the presence of viscous forces during the initial
      transient phase of the droplet interaction with the solid surface even at
      negligible normal velocity, which was verified experimentally using a high-speed
      imaging technique. During this transient phase, for a polystyrene surface, the
      liquid front was observed to be moving with a radial velocity of 0.4 m s(-1),
      which gradually decreased to almost zero after 35 ms. We observed that the
      viscous energy dissipation density is influenced by the surface material and
      topography and the wetting state. The viscous energy dissipation density is
      minimal in the case of the Cassie-Baxter state, while it becomes quite
      significant for the Wenzel state. The viscous effects are reduced for
      topographies with smooth geometries and surfaces with high slip length. 

PMID- 25387064
TI  - Extra- and intra-cranial arterial calcifications in adults depicted as incidental
      findings on cone beam CT images.
AB  - OBJECTIVE: The aim of this study was to evaluate, retrospectively, the gender-
      and age-related prevalence of incidentally found calcifications, depicted within
      the course of the extra- and intra-cranial portion of internal carotid artery
      (ICA), in cone beam computed tomography (CBCT) examinations in adults, and to
      assess their clinical significance. MATERIALS AND METHODS: Out of a pull of 700
      CBCT examinations a total of 484 CBCT scans of adult patients were finally
      selected according to a set of pre-defined criteria. These were evaluated for
      arterial calcifications presence within the ICAs course according to gender and
      age criteria. RESULTS: In total, 492 calcifications were detected: 211 (42.88%)
      extra-cranial and 281 (57.11%) intra-cranial. Those were recorded in 150 scans
      (30.99%) and 161 scans (33.26%), respectively. Calcifications, with either extra-
      or intra-cranial allocation, were found more frequent in males than in females
      (all p-values < 0.05); also patients who presented with positive findings were
      older than those without findings (all p-values < 0.05). Furthermore,
      calcification presence with either extra- or intra-cranial allocation increases
      with age (all p-values < 0.05). CONCLUSION: Significant calcification frequencies
      were found within the ICA's course, in CBCT scans. Moreover, an increased
      incidence of either extra- or intra-cranial presence of these depictions and its
      relation to age and gender was documented.

PMID- 25387066
TI  - Selective multidetection using nanopores.

PMID- 25387065
TI  - Comparison of two theory-based, fully automated telephone interventions designed
      to maintain dietary change in healthy adults: study protocol of a three-arm
      randomized controlled trial.
AB  - BACKGROUND: Health behavior change interventions have focused on obtaining short
      term intervention effects; few studies have evaluated mid-term and long-term
      outcomes, and even fewer have evaluated interventions that are designed to
      maintain and enhance initial intervention effects. Moreover, behavior theory has
      not been developed for maintenance or applied to maintenance intervention design
      to the degree that it has for behavior change initiation. OBJECTIVE: The
      objective of this paper is to describe a study that compared two theory-based
      interventions (social cognitive theory [SCT] vs goal systems theory [GST])
      designed to maintain previously achieved improvements in fruit and vegetable
      (F&V) consumption. METHODS: The interventions used tailored, interactive
      conversations delivered by a fully automated telephony system (Telephone-Linked
      Care [TLC]) over a 6-month period. TLC maintenance intervention based on SCT used
      a skills-based approach to build self-efficacy. It assessed confidence in and
      barriers to eating F&V, provided feedback on how to overcome barriers, plan
      ahead, and set goals. The TLC maintenance intervention based on GST used a
      cognitive-based approach. Conversations trained participants in goal management
      to help them integrate their newly acquired dietary behavior into their
      hierarchical system of goals. Content included goal facilitation, conflict,
      shielding, and redundancy, and reflection on personal goals and priorities. To
      evaluate and compare the two approaches, a sample of adults whose F&V consumption
      was below public health goal levels were recruited from a large urban area to
      participate in a fully automated telephony intervention (TLC-EAT) for 3-6 months.
      Participants who increase their daily intake of F&V by >=1 serving/day will be
      eligible for the three-arm randomized controlled trial. A sample of 405
      participants will be randomized to one of three arms: (1) an assessment-only
      control, (2) TLC-SCT, and (3) TLC-GST. The maintenance interventions are 6
      months. All 405 participants who qualify for the trial will complete surveys
      administered by blinded interviewers at baseline (randomization), 6, 12, 18, and
      24 months. RESULTS: Data analysis is not yet complete, but we hypothesize that
      (1) TLC-GST > TLC-SCT > control at all follow-up time points for F&V consumption,
      and (2) intervention effects will be mediated by the theoretical constructs (eg,
      self-efficacy, goal pursuit, conflict, shielding, and facilitation). CONCLUSIONS:
      This study used a novel study design to initiate and then promote the maintenance
      of dietary behavior change through the use of an evidence-based fully automated
      telephony intervention. After the first 6 months (the acquisition phase), we will
      examine whether two telephony interventions built using different underlying
      behavioral theories were more successful than an assessment-only control group in
      helping participants maintain their newly acquired health behavior change. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT00148525;
      http://clinicaltrials.gov/ct2/show/NCT00148525 (Archived by Webcite at
      http://www.webcitation.org/6TiRriJOs).

PMID- 25387067
TI  - The link between Parkinson's disease and breast and prostate cancers: A meta
      analysis.
AB  - PURPOSE: Clinical observations have shown an increased morbidity for breast
      cancer or prostate cancer in patients with Parkinson's disease (PD), however,
      other reports have noted contradictory results. This pooled analysis was utilized
      to test whether PD is associated with the risk of breast or prostate cancer.
      METHODS: We searched PubMed, Embase and Cochrane library and conducted a meta
      analysis to clarify the correlation of PD with breast and/or prostate cancer
      risk. We identified 16 eligible articles from which odds ratios with 95%
      confident intervals were assessed as main measures in the pooled estimation.
      Subgroup analyses and cumulative meta-analysis were also performed. RESULTS: Our
      results showed no PD risk associated with breast or prostate cancer in the
      overall population, which was supported by the results of cumulative meta
      analyses. The subgroup analyses suggested no significant risk of breast or
      prostate cancer in patients with PD within relevant subsets, i.e. gender,
      ethnicity, PD diagnosis time or study design. No evidence of publication bias was
      observed across the involved studies. CONCLUSIONS: This meta-analysis indicates a
      lack of association between PD and risk of breast or prostate cancer.

PMID- 25387068
TI  - Hospital mortality from atrial fibrillation associated with ischemic stroke: a
      national data report.
AB  - PURPOSE: To study factors associated with poor outcomes in acute ischemic stroke
      patients with atrial fibrillation (AF) by using a national database. MATERIALS
      AND METHODS: This study was a retrospective analytical study by retrieving data
      from the Thailand national database system for universal coverage (UC) health
      insurance system. All adult patients aged over 18 years who were admitted with
      acute ischemic stroke during the fiscal years 2004-2012 by the appropriate ICD
      codes were searched. Eligible patients with AF were categorized as alive or dead
      during hospital stay. The mortality rate and factors associated with in-hospital
      mortality were studied. RESULTS: There were 522,699 patients diagnosed as acute
      stroke; 277,291 patients (53.1%) had acute ischemic stroke. Of those with
      ischemic stroke, 25,319 patients (9.1%) had AF. The mortality rates of acute
      ischemic stroke with AF were 14.1% and without AF were 6.2%, (p < 0.001).
      Significant factors associated with mortality in acute stroke patients with AF by
      multivariate logistic regression were female gender (adjusted odds ratio; AOR
      1.28), co-morbid diseases such as diabetes (AOR 1.28), hypertension (AOR 1.26),
      rt-PA treatment (AOR 0.55), and stroke complications, such as pneumonia (AOR
      2.60), septicemia (AOR 6.50), or gastrointestinal bleeding (AOR 2.16).
      CONCLUSIONS: At the national level, AF caused a higher mortality rate in acute
      ischemic stroke than in non-AF patients. Gender, co-morbid diseases, rt-PA
      treatment, and stroke complications were associated with mortality in acute
      ischemic stroke with AF.

PMID- 25387069
TI  - Meta-analysis of adverse events in recent randomized clinical trials for dimethyl
      fumarate, glatiramer acetate and teriflunomide for the treatment of relapsing
      forms of multiple sclerosis.
AB  - PURPOSE/AIM OF THE STUDY: Trials of dimethyl fumarate (DMF) and teriflunomide,
      two new oral therapies for relapsing-remitting multiple sclerosis (RRMS) were
      recently published [1, 2, 3]. A comparison of their safety against glatiramer
      acetate-a prevalent injectable treatment-is relevant to inform therapy-switching
      decisions. The study objective was to conduct a systematic review and mixed
      treatment comparison of total AEs in RCTs of dimethyl fumarate 240 mg bid (DMF2)
      or tid (DMF3), glatiramer acetate 20 mg injectable daily (GA), and teriflunomide
      7 mg (TERI7) or 14 mg (TERI14) daily in RRMS patients. MATERIALS AND METHODS:
      Articles were selected following Cochrane guidelines. A network meta-analysis was
      used to compare the odds of patients experiencing at least one AE between drugs,
      using placebo as baseline. Drugs were compared using the odds ratio (OR),
      credible interval (CrI), and confidence in OR>=1 (PrOR). The mean rank (best=1)
      and corresponding Surface-Under-Cumulative-Ranking (SUCRA) (best=100%) were
      reported. RESULTS: 3737 patients from three RCTs were included for analysis.
      Patients receiving GA exhibited the lowest AEs (DMF2 [OR=2.67, PrOR=98.7%], DMF3
      [OR=1.92, PrOR=95.3%], Teri7 [OR=2.74, PrOR=95.2%], Teri14 [OR=3.03,
      PrOR=96.4%]), and equivalent to PB (OR=1.60; PrOR=94.3%). No other significant
      differences were found. GA also ranked with the lowest AEs (rank=1.2,
      SUCRA=96.0%), whereas DMF2 and Teri14 ranked highest (rank=4.8). CONCLUSIONS:
      RRMS patients treated with glatiramer have the lowest odds of experiencing AEs,
      while patients taking DMF or teriflunomide have similar, higher odds of
      developing AEs, suggesting that patients treated with glatiramer may have higher
      QoL than patients under DMF or teriflunomide.

PMID- 25387070
TI  - Validation of the nonmotor symptoms questionnaire for Parkinson's disease:
      results from a Chinese pilot study.
AB  - We performed a cross-sectional study of 82 Chinese patients with Parkinson's
      disease (PD) enrolled during an 18-month period. We used a clinical interview to
      evaluate a Chinese version of the nonmotor symptoms questionnaire (NMSQuest) as
      an instrument for measuring the nonmotor symptoms (NMS) in Chinese patients with
      PD. The patients' cognitive deficit, depression/sleep, disease severity and motor
      status were assessed based on the mini-mental state examination (MMSE), the
      Hamilton depression scale (HAMD)/Parkinson's disease sleep scale (PDSS), the
      modified Hoehn and Yahr staging scale (H&Y) and the unified Parkinson's disease
      rating scale part III (UPDRS III), respectively. Thirty items distributed in nine
      different domains of the NMSQuest were evaluated, and the association between the
      NMSQuest and MMSE, H&Y, UPDRS, HAMD and PDSS was identified. Significant
      correlations were observed between the NMSQuest and disease duration (rs = 0.272,
      p = 0.013), UPDRS total score (rs = 0.444, p < 0.001), UPDRS II (rs = 0.415, p <
      0.001) and UPDRS III (rs = 0.228, p = 0.039). Furthermore, the sleep disorder and
      mood (depression/anxiety) domain of the NMSQuest were significantly correlated
      with the PDSS (rs = -0.471, p < 0.001) and HAMD (rs = 0.687, p < 0.001),
      respectively. Our results indicate that the Chinese version of the NMSQuest, a
      useful screening tool, can be considered as a comprehensive, practical measure
      for NMS evaluation in Chinese PD patients. The NMSQuest highlights the prevalence
      of the wide range of NMS and indicated good responsiveness and interpretability.
      We strongly recommend routine use of the simplified Chinese version of NMSQuest
      in this country. 

PMID- 25387071
TI  - Cryptogenic focal epilepsy and "hidden" celiac disease in adulthood: a causal or
      accidental link?
AB  - PURPOSE: Celiac disease (CD) is an immuno-mediated small bowel disease
      characterized by chronic inflammation due to a permanent intolerance to gliadin.
      Several neurological complications have been described, including epilepsy, whose
      evolution might often improve by adopting gluten-free diet (GFD). We studied a
      population of adult patients affected by posterior drug-resistant epilepsy of
      unknown cause by performing an accurate screening for CD. In the selected
      patients presenting the association of epilepsy and CD, we characterized the
      related electro-clinical features. MATERIALS AND METHODS: We consecutively
      identified 211 adult subjects affected by drug-resistant cryptogenic focal
      epilepsy with posterior seizures. All these patients underwent serological
      screening for CD. In 10 subjects positive serological tests allowed to perform a
      CD diagnosis (confirmed by duodenal biopsy). For each patient clinical and EEG
      data, neuroimaging studies, serological and histological findings were revised,
      as well as response to GFD, defined as an improvement in seizure outcome.
      RESULTS: A significant delay between diagnosis of epilepsy and CD was documented.
      Visual ictal manifestations were reported in half of subjects. In all cases,
      interictal EEG showed slow and epileptiform abnormalities over parietal-occipital
      and temporal regions; in three cases, FOS phenomenon was observed. Four patients
      had familiar history of CD and six cases showed clinical signs/symptoms of
      malabsorption. GFD led to a reduction of seizure frequency in half of patients.
      CONCLUSIONS: "Posterior" ictal semiology, peculiar EEG patterns and drug
      resistance emerge as the most interesting characteristics. CD screening should be
      performed in epilepsy patients presenting such features.

PMID- 25387072
TI  - Comparative electromyography analysis of the upper extremity between
      inexperienced and elite water polo players during an overhead shot.
AB  - The aim of this study was to compare muscle activity patterns between
      inexperienced and experienced water polo players while taking an overhead shot.
      The study was carried out with a group of 12 water polo players and an
      inexperienced group of 10 healthy participants. Signals were recorded by surface
      electromyography from six different muscles. The average and standard deviation
      of the normalized electrical activity, time to peak, time broadness, and muscle
      sequencing during the overhead shot were determined for each muscle in both
      groups and compared with each other. In water polo players, the normalized
      electrical activities of triceps brachii, pectoralis major, and wrist flexors
      were greater than other muscles, while in the inexperienced group the triceps
      brachii specifically played an important role. There was minimal activation of
      the middle deltoid and biceps brachii in water polo players. Increased times to
      peak and time broadness of muscles were found in the inexperienced group compared
      to experienced water polo players; this difference may be explained by different
      neuromuscular proprioception. Only experienced water polo players activated the
      observed muscles in a specific sequence, from proximal to distal. Therefore,
      coaches should emphasize smooth and quick transitions from proximal to distal
      segments, with less importance placed on individual muscle strengthening. 

PMID- 25387073
TI  - An uncleaved signal peptide directs the Malus xiaojinensis iron transporter
      protein Mx IRT1 into the ER for the PM secretory pathway.
AB  - Malus xiaojinensis iron-regulated transporter 1 (Mx IRT1) is a highly effective
      inducible iron transporter in the iron efficient plant Malus xiaojinensis. As a
      multi-pass integral plasma membrane (PM) protein, Mx IRT1 is predicted to consist
      of eight transmembrane domains, with a putative N-terminal signal peptide (SP) of
      1-29 amino acids. To explore the role of the putative SP, constructs expressing
      Mx IRT1 (with an intact SP) and Mx DsIRT1 (with a deleted SP) were prepared for
      expression in Arabidopsis and in yeast. Mx IRT1 could rescue the iron-deficiency
      phenotype of an Arabidopsis irt1 mutant, and complement the iron-limited growth
      defect of the yeast mutant DEY 1453 (fet3fet4). Furthermore, fluorescence
      analysis indicated that a chimeric Mx IRT1-eGFP (enhanced Green Fluorescent
      Protein) construct was translocated into the ER (Endoplasmic reticulum) for the
      PM sorting pathway. In contrast, the SP-deleted Mx DsIRT1 could not rescue either
      of the mutant phenotypes, nor direct transport of the GFP signal into the ER.
      Interestingly, immunoblot analysis indicated that the SP was not cleaved from the
      mature protein following transport into the ER. Taken together, data presented
      here provides strong evidence that an uncleaved SP determines ER-targeting of Mx
      IRT1 during the initial sorting stage, thereby enabling the subsequent transport
      and integration of this protein into the PM for its crucial role in iron uptake. 

PMID- 25387074
TI  - Long non-coding RNAs: critical players in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a complex disease with multiple underlying
      pathogenic mechanisms caused by a variety of etiologic factors. Emerging evidence
      showed that long non-coding RNAs (lncRNAs), with size larger than 200 nucleotides
      (nt), play important roles in various types of cancer development and
      progression. In recent years, some dysregulated lncRNAs in HCC have been revealed
      and roles for several of them in HCC have been characterized. All these findings
      point to the potential of lncRNAs as prospective novel therapeutic targets in
      HCC. In this review, we summarize known dysregulated lncRNAs in HCC, and review
      potential biological roles and underlying molecular mechanisms of lncRNAs in HCC.
      Additionally, we discussed prospects of lncRNAs as potential biomarker and
      therapeutic target for HCC. In conclusion, this paper will help us gain better
      understanding of molecular mechanisms by which lncRNAs perform their function in
      HCC and also provide general strategies and directions for future research. 

PMID- 25387075
TI  - The effects of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and
      function after glutamate excitotoxicity.
AB  - NAD+ is an essential co-enzyme for cellular energy metabolism and is also
      involved as a substrate for many cellular enzymatic reactions. It has been shown
      that NAD+ has a beneficial effect on neuronal survival and brain injury in in
      vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial
      biogenesis and function in ischemia has not been well investigated. In the
      present study, we used an in vitro glutamate excitotoxicity model of primary
      cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death
      and mitochondrial biogenesis and function. Our results show that supplementation
      of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing
      factor translocation after neurons were challenged with excitotoxic glutamate
      stimulation. Using different approaches including confocal imaging, mitochondrial
      DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that
      NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation
      and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment
      effectively inhibited mitochondrial membrane potential depolarization and NADH
      redistribution after excitotoxic glutamate stimulation. Taken together, our
      results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death
      after glutamate excitotoxicity via preserving mitochondrial biogenesis and
      integrity. Our findings provide insights into potential neuroprotective
      strategies in ischemic stroke. 

PMID- 25387076
TI  - Spectroscopic studies of R(+)-alpha-lipoic acid--cyclodextrin complexes.
AB  - alpha-Lipoic acid (ALA) has a chiral center at the C6 position, and exists as two
      enantiomers, R(+)-ALA (RALA) and S(-)-ALA (SALA). RALA is naturally occurring,
      and is a cofactor for mitochondrial enzymes, therefore playing a major role in
      energy metabolism. However, RALA cannot be used for pharmaceuticals or
      nutraceuticals because it readily polymerizes via a 1,2-dithiolane ring-opening
      when exposed to light or heat. So, it is highly desired to find out the method to
      stabilize RALA. The purpose of this study is to provide the spectroscopic
      information of stabilized RALA and SALA through complexation with cyclodextrins
      (CDs), alpha-CD, beta-CD and gamma-CD and to examine the physical characteristics
      of the resultant complexes in the solid state. The RALA-CD structures were
      elucidated based on the micro fourier transform infrared (FT-IR) and Raman
      analyses. The FT-IR results showed that the C=O stretching vibration of RALA
      appeared at 1717 cm-1 and then shifted on formation of the RALA-CD complexes. The
      Raman spectra showed that the S-S and C-S stretching vibrations for RALA at 511
      cm-1 (S-S), 631 cm-1 (C-S) and 675 cm-1 (C-S) drastically weakened and almost
      disappeared upon complexation with CDs. Several peaks indicative of O-H
      vibrations also shifted or changed in intensity. These results indicate that RALA
      and CDs form host-guest complexes by interacting with one another.

PMID- 25387077
TI  - MicroRNA-130b promotes cell aggressiveness by inhibiting peroxisome proliferator
      activated receptor gamma in human hepatocellular carcinoma.
AB  - MircroRNA-130b (miR-130b) is proposed as a novel tumor-related miRNA and has been
      found to be significantly dysregulated in tumors. In this study, the expression
      level of miR-130b was found to be obviously higher in hepatocellular carcinoma
      (HCC) tissues than that in nontumor tissues. Further, miR-130b was expressed at
      significantly higher levels in aggressive and recurrent tumor tissues. Clinical
      analysis indicated that high-expression of miR-130b was prominently correlated
      with venous infiltration, high Edmondson-Steiner grading and advanced tumor-node
      metastasis (TNM) tumor stage in HCC. Elevated miR-130b expression was observed in
      all HCC cell lines (HepG2, SMMC-7721, Huh7, Hep3B and MHCC97H) as compared with
      that in a nontransformed hepatic cell line (LO2). Furthermore, an inverse
      correlation between miR-130b and E-cadherin and a positive correlation between
      miR-130b and Vimentin were observed in HCC tissues. Down-regulation of miR-130b
      expression reduced invasion and migration in both Hep3B and MHCC97H cells.
      Peroxisome proliferator-activated receptor gamma (PPAR-gamma) was inversely
      correlated with miR-130b expression in HCC tissues. In addition, down-regulation
      of miR-130b restored PPAR-gamma expression and subsequently suppressed epithelial
      mesenchymal transition (EMT) in HCC cells. We identified PPARgamma as a direct
      target of miR-130b in HCC in vitro. Notably, PPAR-gamma knockdown abolished down
      regulation of miR-130b-inhibited EMT in MHCC97H cells. In conclusion, miR-130b
      may promote HCC cell migration and invasion by inhibiting PPAR-gamma and
      subsequently inducing EMT. 

PMID- 25387078
TI  - Multiple mechanisms mediate resistance to sorafenib in urothelial cancer.
AB  - Genetic and epigenetic changes in the mitogen activated protein kinase (MAPK)
      signaling render urothelial cancer a potential target for tyrosine kinase
      inhibitor (TKI) treatment. However, clinical trials of several TKIs failed to
      prove efficacy. In this context, we investigated changes in MAPK signaling
      activity, downstream apoptotic regulators and changes in cell cycle distribution
      in different urothelial cancer cell lines (UCCs) upon treatment with the
      multikinase inhibitor sorafenib. None of the classical sorafenib targets
      (vascular endothelial growth factor receptor 1/-receptor 2, VEGFR1/-R2; platelet
      derived growth factor receptor alpha/-receptor beta, PDGFR-alpha/-beta; c-KIT)
      was expressed at significant levels leaving RAF proteins as its likely molecular
      target. Low sorafenib concentrations paradoxically increased cell viability,
      whereas higher concentrations induced G1 arrest and eventually apoptosis. MAPK
      signaling remained partly active after sorafenib treatment, especially in T24
      cells with an oncogenic HRAS mutation. AKT phosphorylation was increased,
      suggesting compensatory activation of the phosphatidylinositol-3-kinase (PI3K)
      pathway. Sorafenib regularly down regulated the anti-apoptotic myeloid cell
      leukemia 1 (Mcl-1) protein, but combinatorial treatment with ABT-737 targeting
      other B-cell lymphoma 2 (Bcl-2) family proteins did not result in synergistic
      effects. In summary, efficacy of sorafenib in urothelial cancer cell lines
      appears hampered by limited effects on MAPK signaling, crosstalk with further
      cancer pathways and an anti-apoptotic state of UCCs. These observations may
      account for the lack of efficacy of sorafenib in clinical trials and should be
      considered more broadly in the development of signaling pathway inhibitors for
      drug therapy in urothelial carcinoma. 

PMID- 25387081
TI  - Elucidation of dietary risk factors in osteoarthritis knee-a case-control study.
AB  - BACKGROUND AND OBJECTIVE: Nutritional imbalance, combined with endocrine
      abnormalities, may be involved in the pathogenesis of osteoarthritis (OA). This
      study was conducted to determine the association of OA with dietary factors, such
      as quantity and quality of nutrient intake. METHODS: This case-control study
      enrolled 180 knee osteoarthritis (KOA) subjects who met the American College of
      Rheumatology definition of KOA, with an equal number of matched controls. Outcome
      measures, such as dietary nutrient intake and its frequency, were recorded using
      a food frequency questionnaire. RESULTS: Compared to controls, cases were older
      individuals with a higher body mass index (BMI). Physical activity scores were
      lower in female cases compared to male cases and controls. A significantly higher
      intake of phosphorus and fat was observed in overall cases (fat in females only).
      A significantly lower intake of vitamin C and vitamin D was observed in overall
      cases and the significance of vitamin D persisted on gender-wise bifurcation. On
      multiple logistic regression analysis, the intake of vitamin D (odds ratio [OR] =
      0.79) and vitamin C (OR = 0.97) was inversely associated with the presence of KOA
      in the observation group, especially in females. Generally, the intake of food
      servings/day, green leafy vegetables (GLVs), and fats/oils was higher, whereas
      the intake of fruits, milk/milk products, and meat/poultry was lower in cases
      compared to controls. CONCLUSION: Low intake of vitamin D and vitamin C is a
      possible risk factor for KOA. Certain food groups, such as fruits, milk/milk
      products, and meat/poultry are beneficial for KOA. Further studies are needed to
      elucidate the associations between diet and KOA.

PMID- 25387079
TI  - Gliadin peptides as triggers of the proliferative and stress/innate immune
      response of the celiac small intestinal mucosa.
AB  - Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic
      background, caused by gliadin-containing food. Undigested gliadin peptides induce
      innate and adaptive T cell-mediated immune responses. The major mediator of the
      stress and innate immune response to gliadin peptides (i.e., peptide 31-43, P31
      43) is the cytokine interleukin-15 (IL-15). The role of epithelial growth factor
      (EGF) as a mediator of enterocyte proliferation and the innate immune response
      has been described. In this paper, we review the most recent literature on the
      mechanisms responsible for triggering the up-regulation of these mediators in CD
      by gliadin peptides. We will discuss the role of P31-43 in enterocyte
      proliferation, structural changes and the innate immune response in CD mucosa in
      cooperation with EGF and IL-15, and the mechanism of up-regulation of these
      mediators related to vesicular trafficking. We will also review the literature
      that focuses on constitutive alterations of the structure,
      signalling/proliferation and stress/innate immunity pathways of CD cells.
      Finally, we will discuss how these pathways can be triggered by gliadin peptide
      P31-43 in controls, mimicking the celiac cellular phenotype. 

PMID- 25387082
TI  - Silicon carbide coated with TiO2 with enhanced cobalt active phase dispersion for
      Fischer-Tropsch synthesis.
AB  - The introduction of a thin layer of TiO2 on beta-SiC allows a significant
      improvement of the cobalt dispersion. This catalyst exhibits an excellent and
      stable catalytic activity for the Fischer-Tropsch synthesis (FTS) with high C5+
      selectivity, which contributes to the development of a new active catalyst family
      in the gas-to-liquid process. 

PMID- 25387083
TI  - Unfolding stabilities of two structurally similar proteins as probed by
      temperature-induced and force-induced molecular dynamics simulations.
AB  - Unfolding stabilities of two homologous proteins, cardiotoxin III and short
      neurotoxin (SNTX) belonging to three-finger toxin (TFT) superfamily, have been
      probed by means of molecular dynamics (MD) simulations. Combined analysis of data
      obtained from steered MD and all-atom MD simulations at various temperatures in
      near physiological conditions on the proteins suggested that overall structural
      stabilities of the two proteins were different from each other and the MD results
      are consistent with experimental data of the proteins reported in the literature.
      Rationalization for the differential structural stabilities of the structurally
      similar proteins has been chiefly attributed to the differences in the structural
      contacts between C- and N-termini regions in their three-dimensional structures,
      and the findings endorse the 'CN network' hypothesis proposed to qualitatively
      analyse the thermodynamic stabilities of proteins belonging to TFT superfamily of
      snake venoms. Moreover, the 'CN network' hypothesis has been revisited and the
      present study suggested that 'CN network' should be accounted in terms of
      'structural contacts' and 'structural strengths' in order to precisely describe
      order of structural stabilities of TFTs. 

PMID- 25387084
TI  - Characterization of thin poly(dimethylsiloxane)-based tissue-simulating phantoms
      with tunable reduced scattering and absorption coefficients at visible and near
      infrared wavelengths.
AB  - Optical phantoms are used in the development of various imaging systems. For
      certain applications, the development of thin phantoms that simulate the physical
      size and optical properties of tissue is important. Here, we demonstrate a method
      for producing thin phantom layers with tunable optical properties using
      poly(dimethylsiloxane) (PDMS) as a substrate material. The thickness of each
      layer (between 115 and 880 MUm) was controlled using a spin coater. The reduced
      scattering and absorption coefficients were controlled using titanium dioxide and
      alcohol-soluble nigrosin, respectively. These optical coefficients were
      quantified at six discrete wavelengths (591, 631, 659, 691, 731, and 851 nm) at
      varying concentrations of titanium dioxide and nigrosin using spatial frequency
      domain imaging. From the presented data, we provide lookup tables to determine
      the appropriate concentrations of scattering and absorbing agents to be used in
      the design of PDMS-based phantoms with specific optical coefficients. In
      addition, heterogeneous phantoms mimicking the layered features of certain tissue
      types may be fabricated from multiple stacked layers, each with custom optical
      properties. These thin, tunable PDMS optical phantoms can simulate many tissue
      types and have broad imaging calibration applications in endoscopy, diffuse
      optical spectroscopic imaging, and optical coherence tomography, etc.

PMID- 25387085
TI  - Determinants of nephrostomy tube dislodgment after percutaneous nephrolithotomy.
AB  - BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PCNL) traditionally
      necessitates the placement of a nephrostomy tube at the conclusion of the
      surgical procedure. Although tubeless PCNL has become more popular, patients with
      complex problems still need traditional nephrostomy tube drainage. The goal of
      this study was to investigate whether patient body mass index (BMI) impacted
      inadvertent nephrostomy tube dislodgement. Furthermore, we hoped to determine
      whether nephrostomy tube type impacted tube dislodgement rates. METHODS: A
      retrospective review between 2005 and 2012 of 475 consecutive PCNL cases was
      undertaken. Patients were categorized based on the type of nephrostomy tube
      placed. BMI was examined as a continuous variable. The primary outcome of
      nephrostomy tube dislodgment was determined based on imaging obtained at the time
      of PCNL and postoperative hospitalization. Logistic regression analysis was then
      used to adjust for nephrostomy tube type and BMI. RESULTS: Overall, 24 (5.5%)
      total patients experienced nephrostomy tube dislodgment postoperatively. The mean
      BMI for patients experiencing nephrostomy tube dislodgment was 39.7 vs 30.9 for
      those without tube dislodgment (P<0.0001; 95% confidence interval [CI] 4.6 to
      12.9). Using logistic regression and adjusting for the use tube type, BMI was an
      independent predictor of tube dislodgement (P<0.001). For each unit of increase
      in BMI, the likelihood of tube dislodgment increased by 6% (1.06). After
      adjusting for BMI, however, nephrostomy tube type was not found to be an
      independent predictor of nephrostomy tube dislodgment. CONCLUSIONS: Nephrostomy
      tube type did not influence nephrostomy tube dislodgment rates. As a patient's
      BMI increased, the likelihood of tube dislodgment increased in a directly
      proportionate fashion. This is possibly because of the nephrostomy tube being
      fixed directly to the mobile skin associated with their fat pannus. Although the
      nephrostomy tube type itself did not affect tube dislodgment rates, a redesigned
      nephrostomy tube or fixation device should take into account the above findings
      related to obese patients to reduce the likelihood of nephrostomy tube
      dislodgment.

PMID- 25387086
TI  - The amino acids 736-761 of the MERS-CoV spike protein induce neutralizing
      antibodies: implications for the development of vaccines and antiviral agents.
AB  - Based on a bioinformatics analysis of the Middle East respiratory syndrome
      coronavvirus (MERS-CoV) S protein, we synthesized a panel of peptides coupled to
      keyhole limpet haemocyanin and used them to raise antibodies in rabbits. In
      addition, the recombinant receptor-binding domain (RBD) was used to raise
      polyclonal antibodies in mice. All of the antibodies raised by S-peptide
      immunisation were specific and sensitive for S protein expressed in transfected
      cells in the indirect immunofluorescence assay or Western blotting. The RBD
      efficiently elicited neutralizing antibodies against MERS-CoV by blocking viral
      entry at the binding step. Furthermore, we found that the SP3 peptide,
      corresponding to amino-acid residues 736-761 of the S protein, elicited robust
      neutralizing activities by blocking viral entry at the postbinding and membrane
      fusion steps. We conclude that amino-acid residues 736-761 of the S protein carry
      neutralizing epitopes that may be used in the development of vaccines and
      antiviral agents against MERS-CoV.

PMID- 25387087
TI  - Clinical and biological predictors of outcome following relapse of CML post-allo
      SCT.
AB  - Although there are now fewer allo-SCTs performed for CML, leukemic relapse post
      transplant remains a persistent problem. To better define clinical and biological
      parameters determining postrelapse outcome, we studied 59 patients with CML
      relapsing after HLA-identical sibling allo-SCT between 1993 and 2008. Eighteen
      (30.5%) were transplanted in advanced phase and 41 (69.5%) in chronic phase. With
      a median follow-up from relapse of 7.9 years, 5-year post relapse survival (PRS)
      was 62%. Multivariate analysis found disease status at transplant, time to
      diagnosis of relapse from transplant and pretransplant tyrosine kinase inhibitor
      (TKI) use as significant factors associated with PRS. Analysis of BCR-ABL
      transcript expression in the hematopoietic progenitor compartment was performed
      in 36 patients (22 relapsed, 8 non-relapsed and 6 TKI alone controls). Patients
      with BCR-ABL expression in their early hematopoietic stem cell compartment
      (Lineage(-)CD34(+)CD38(-)CD90(+)) had worse survival irrespective of the disease
      status. We conclude that disease status remains the strongest clinical prognostic
      factor for PRS in CML following allo-SCT. The persistence of BCR-ABL expression
      in the progenitor cell compartment in some patients after SCT emphasizes the need
      to target CML-leukemia stem cells. 

PMID- 25387088
TI  - Trends in autologous hematopoietic cell transplantation for multiple myeloma in
      Europe: increased use and improved outcomes in elderly patients in recent years.
AB  - Autologous hematopoietic cell transplantation (AHCT) is a standard of care in
      multiple myeloma (MM) patients aged <65 years. To understand age-related trends
      in utilisation and outcome of AHCT, we analysed 53 675 MM patients who underwent
      a first AHCT in 31 European countries between 1991 and 2010. The number of
      patients undergoing AHCT increased for all age groups (<40, 40-49, 50-59, 60-64,
      65-69 and ?70 years) throughout the observation period. The highest increase was
      observed for patients aged ?65 years, who accounted for 3% of AHCTs in 1991-1995
      and for 18.8% of AHCTs in 2006-2010. Risk factors associated with survival over
      the entire observation period (P<0.001) were calendar period, remission status at
      AHCT, gender, disease duration before AHCT and age. Survival improved
      considerably more in older than in younger patients in recent years. In 2006
      2010, median 2- and 5-year post-transplant survival ranged from 85.9 and 61.5% in
      patients <40 years to 80.2 and 49.7% in those ?70 years. All-cause day-100
      mortality decreased throughout the observation period to ?2.4% for all age groups
      in 2006-2010. The results of this study demonstrate increased utilisation and
      safety of AHCT with improved post-transplant survival particularly in elderly MM
      patients in recent years in Europe. 

PMID- 25387089
TI  - Chimerism analysis in peripheral blood using indel quantitative real-time PCR is
      a useful tool to predict post-transplant relapse in acute leukemia.
AB  - Detection of increasing mixed chimerism (IMC) using standard PCR correlates with
      relapse after allo-SCT for acute leukemias (ALs). Quantitative real-time PCR of
      insertion/deletion polymorphism (indel qrtPCR) is a much more sensitive method,
      which can be performed on peripheral blood. We studied the significance of low
      increases of recipient cells (0.1%) detected by indel qrtPCR in a cohort of 89
      transplants. We did not observe relapse among the 32 patients with no IMC. Fifty
      seven patients presented a first IMC, which was followed by four different
      scenarios: a decreasing MC (26 cases, no relapse), a stable MC (1 case, 1
      relapse), a second IMC (24 cases, 15 relapse) or no control of chimerism (6
      cases, 5 relapses). In multivariate analysis, detection of two successive IMCs
      was strongly associated with relapse (hazard ratio (HR): 9.4, 95% confidence
      interval (CI): 3.8-23; P<0.0001). Among the 57 patients who presented at least
      one IMC, 27 underwent immunomodulation (tapering of immunosuppression or donor
      lymphocyte injection), leading to a 1-year relapse rate of 15.7% vs 57.6% in the
      30 other patients (P=0.0007). Altogether, these results indicate that chimerism
      analysis using indel qrtPCR in peripheral blood is a useful tool for detection of
      relapse in patients transplanted for AL. 

PMID- 25387091
TI  - The impact of center accreditation on hematopoietic cell transplantation (HCT).
AB  - There are two voluntary center-accrediting organizations in the USA, the
      Foundation for the Accreditation of Cellular Therapy (FACT) and core Clinical
      Trial Network (CTN) certification, that are thought to improve and ensure
      hematopoietic cell transplantation (HCT) center quality care and certify clinical
      excellence. We sought to observe whether there are differences in outcomes
      between HLA-matched and -mismatched HCT by CTN and FACT status. Using the 2008
      2010 Center for International Blood & Marrow Transplant Research data we created
      three center categories: non-FACT centers (24 centers), FACT-only certified
      centers (106 centers) and FACT and core clinical trial network (FACT/CTN)
      certified centers (32 centers). We identified patient characteristics within
      these centers and the relationship between FACT certification and survival. Our
      cohort consisted of 12 993 transplants conducted in 162 centers. After adjusting
      for patient and center characteristics we found that FACT/CTN centers had
      consistently superior results relative to non-FACT and FACT-only centers (P<0.05)
      especially for more complex HCT. However, non-FACT centers were comparable to
      FACT-only centers for matched related and unrelated patients. Although FACT
      status is an important standard of quality control that begins to define improved
      OS, our results indicate that FACT status alone is not an indicator for superior
      outcomes. 

PMID- 25387090
TI  - SCT for severe autoimmune diseases: consensus guidelines of the European Society
      for Blood and Marrow Transplantation for immune monitoring and biobanking.
AB  - Over the past 15 years, SCT has emerged as a promising treatment option for
      patients with severe autoimmune diseases (ADs). Mechanistic studies recently
      provided the proof-of-concept that restoration of immunological tolerance can be
      achieved by haematopoietic SCT in chronic autoimmunity through eradication of the
      pathologic, immunologic memory and profound reconfiguration of the immune system,
      that is, immune 'resetting'. Nevertheless, a number of areas remain unresolved
      and warrant further investigation to refine our understanding of the underlying
      mechanisms of action and to optimize clinical SCT protocols. Due to the low
      number of patients transplanted in each centre, it is essential to adequately
      collect and analyse biological samples in a larger cohort of patients under
      standardized conditions. The European society for blood and marrow
      transplantation Autoimmune Diseases and Immunobiology Working Parties have,
      therefore, undertaken a joint initiative to develop and implement guidelines for
      'good laboratory practice' in relation to procurement, processing, storage and
      analysis of biological specimens for immune reconstitution studies in AD patients
      before, during and after SCT. The aim of this document is to provide practical
      recommendations for biobanking of samples and laboratory immune monitoring in
      patients with ADs undergoing SCT, both for routine supportive care purposes and
      investigational studies. 

PMID- 25387092
TI  - The impact of improved JACIE standards on the care of related BM and PBSC donors.
AB  - Discrepancies exist between the care of unrelated donors (UDs) and related donors
      (RDs), particularly regarding medical suitability criteria, consenting procedures
      and donor follow-up. Changes to the most recent JACIE standards have addressed
      these issues. We studied 208 RDs who underwent PBSC or BM donation in a single
      centre during 2004-2013 to determine the impact of regulatory changes on donor
      care, and assessed the safety and efficacy of stem cell donation in donors not
      meeting UD medical suitability criteria. We observed significant improvements in
      donor consenting procedures (P=0.003) and donor follow-up (P=0.007) after
      stipulations in these areas were introduced. We saw a higher incidence of serious
      adverse events (SAEs) in RDs not meeting UD suitability criteria (P=0.018), and a
      higher incidence of SAEs in donors ?60 years (P=0.020). Haematopoietic progenitor
      cell donation is less safe in RDs who do not meet UD criteria for medical
      suitability. Although changes to JACIE standards have improved practice,
      development of specific medical suitability for RDs and guidelines around 'grey
      areas' where risks to a donor are unclear or theoretical, will be important in
      improving RD safety and standardising practice. 

PMID- 25387093
TI  - Dendritic cell reconstitution is associated with relapse-free survival and acute
      GVHD severity in children after allogeneic stem cell transplantation.
AB  - DCs are potent APCs and key regulators of innate and adaptive immunity. After
      allo-SCT, their reconstitution in the peripheral blood (PB) to levels similar to
      those in healthy individuals tends to be slow. We investigate the age- and sex
      dependant immune reconstitution of myeloid (mDC) and plasmacytoid DC (pDC) in the
      PB of 45 children with leukaemia or myelodysplastic syndrome (aged 1-17 years,
      median 10) after allo-SCT with regard to relapse, acute GVHD (aGVHD) and relapse
      free survival. Low pDC/MUL PB up to day 60 post SCT are associated with higher
      incidence of moderate or severe aGVHD (P=0.035), whereas high pDC/MUL PB up to
      day 60 are associated with higher risk of relapse (P<0.001). The time-trend of
      DCs/MUL PB for days 0-200 is a significant predictor of relapse-free survival for
      both mDCs (P<0.001) and pDCs (P=0.020). Jointly modelling DC reconstitution and
      complications improves on these simple criteria. Compared with BM, PBSC
      transplants tend to show slower mDC/pDC reconstitution (P=0.001, 0.031,
      respectively), but have no direct effect on relapse-free survival. These results
      suggest an important role for both mDCs and pDCs in the reconstituting immune
      system. The inclusion of mDCs and pDCs may improve existing models for
      complication prediction following allo-SCT. 

PMID- 25387094
TI  - Outcome of children with high-risk acute myeloid leukemia given autologous or
      allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.
AB  - We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1
      enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO;
      n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the
      availability of a HLA-compatible sibling. Infants, patients with AML-M7, or
      complex karyotype or those with FLT3-ITD, were eligible to be transplanted also
      from alternative donors. All patients received a myeloablative regimen combining
      busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received
      BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM
      in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57
      months (range 12-130), the probability of disease-free survival (DFS) was 73% and
      63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although
      the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT
      recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both
      groups. Patients transplanted with unrelated donor cord blood had a remarkable
      92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a
      suitable option for preventing leukemia recurrence in HR children with CR1 AML.

PMID- 25387095
TI  - Chronic GVHD induced GVL effect after unmanipulated haploidentical hematopoietic
      SCT for AML and myelodysplastic syndrome.
AB  - The aim of this study was to investigate the impact of occurrence of chronic GVHD
      (cGVHD) and its severity on transplantation outcomes in a consecutive cohort of
      AML and myelodysplastic syndrome (MDS) patients who received unmanipulated
      haploidentical hematopoietic SCT (haplo-HSCT; n=324). The cumulative incidence of
      relapse was significantly decreased in patients with cGVHD compared with the non
      cGVHD group (1 year: 3.2% vs 11.9%, P=0.002; 3 years: 6.0% vs 16.3%, P=0.002),
      particularly in those with mild cGVHD. The cumulative incidence of non-relapse
      mortality was comparable between patients with and without cGVHD. The
      probabilities of disease-free survival (DFS) were significantly better in
      patients with cGVHD than in those in the non-cGVHD group (1 year: 90.5% vs 78.5%,
      P=0.002; 3 years: 86.5% vs 71.5%, P<0.001), particularly in those with mild or
      moderate cGVHD; however, no significant impact of severe cGVHD on DFS was seen.
      Our findings highlight the close relationship between cGVHD and the immune
      mediated GVL effect in patients with AML and MDS receiving unmanipulated haplo
      HSCT; however, only mild or moderate cGVHD was associated with a lower risk of
      relapse translating into improved DFS. 

PMID- 25387096
TI  - Monitoring mycophenolate mofetil is necessary for the effective prophylaxis of
      acute GVHD after cord blood transplantation.

PMID- 25387097
TI  - Chronic GVHD and concurrent new-onset nephrotic syndrome in allogeneic transplant
      recipients. Incidence, pattern and therapeutic outcomes.

PMID- 25387098
TI  - Onset and outcome of pregnancy after autologous haematopoietic SCT (AHSCT) for
      autoimmune diseases: a retrospective study of the EBMT autoimmune diseases
      working party (ADWP).
AB  - Autologous haematopoietic SCT (AHSCT) is increasingly used to control severe and
      refractory autoimmune diseases (AD). Many patients are women of reproductive age
      with a potential desire for children. We present a multicentre retrospective
      analysis of pregnancy and childbirth in patients who underwent AHSCT for AD. The
      databases of the European Blood and Marrow Transplantation and University of Sao
      Paulo, Ribeirao Preto, Brazil were searched for female patients aged 18-50 years
      who had received AHSCT for AD between 1994-2011. In 324 adult female patients, 22
      pregnancies were reported in 15 patients between 1997-2011. Indications for AHSCT
      included multiple sclerosis (n=7), systemic sclerosis (n=5), rheumatoid arthritis
      (n=1), juvenile idiopathic arthritis (n=1) and Takayasu disease (n=1). Of the 22
      reported pregnancies, 20 followed natural conception. 15 pregnancies (68%)
      resulted in healthy life births, whereas 7 (32%) failed. Exacerbations of AD
      occurred in two patients during second pregnancies. No maternal mortality was
      associated with pregnancy or postpartum. There were no reports of congenital,
      developmental or any other disease in the children. This retrospective analysis
      confirms the possibility of pregnancy and childbirth following AHSCT for severe
      AD. The outcome of pregnancy is generally good and most led to the birth of a
      healthy child. 

PMID- 25387099
TI  - Porous ceramic tablet embedded with silver nanopatches for low-cost point-of-use
      water purification.
AB  - This work describes a novel method to embed silver in ceramic porous media in the
      form of metallic silver nanopatches. This method has been applied to develop a
      new POU technology, a silver-infused ceramic tablet that provides long-term water
      disinfection. The tablet is fabricated using clay, water, sawdust, and silver
      nitrate. When dropped into a household water storage container, the ceramic
      tablet releases silver ions at a controlled rate that in turn disinfect microbial
      pathogens. Characterization of the silver-embedded ceramic media was performed
      using transmission electron microscopy. Spherical-shaped patches of metallic
      silver were observed at 1-6 nm diameters and confirmed to be silver with energy
      dispersive spectroscopy. Disinfection experiments in a 10 L water volume
      demonstrated a 3 log reduction of Escherichia coli within 8 h while silver levels
      remained below the World Health Organization drinking water standard (0.1 mg/L).
      Silver release rate varied with clay mineralogy, sawdust particle size, and
      initial silver mass. Silver release was repeatable for daily 10 L volumes for 154
      days. Results suggest the ceramic tablet can be used to treat a range of water
      volumes. This technology shows great potential to be a low-cost, simple-to-use
      water treatment method to provide microbiologically safe drinking water at the
      household level.

PMID- 25387101
TI  - Swimming exercise enhances the hippocampal antioxidant status of female Wistar
      rats.
AB  - OBJECTIVES: Moderate exercise is known to have health benefits, while both
      sedentarism and strenuous exercise have pro-oxidant effects. In this study, we
      assessed the effect of moderate exercise on the antioxidant homeostasis of rats'
      hippocampi. METHODS: Female Wistar rats were submitted to a 30-minute swimming
      protocol on 5 days a week, for 4 weeks. Control rats were immersed in water and
      carefully dried. Production of hippocampal reactive species, activity of
      antioxidant enzymes, and glutathione levels in these animals were determined up
      to 30 days after completion of the 4-week protocol. RESULTS: Production of
      reactive species and hippocampal glutathione levels were increased 1 day after
      completion of the 4-week protocol, and returned to control levels after 7 days.
      Antioxidant enzyme activities were increased both 1 day (catalase) and 7 days
      (superoxide dismutase and glutathione peroxidase) after completion of the
      protocol. Thirty days after completion of the protocol, none of the antioxidant
      parameters evaluated differed from those of controls. DISCUSSION: Our results
      reinforce the benefits of aerobic exercise, which include positive modulation of
      antioxidant homeostasis in the hippocampi. The effects of exercise are not
      permanent; rather, an exercise regimen must be continued in order to maintain the
      neurometabolic adaptations.

PMID- 25387102
TI  - Synthesis, structure, and properties of supramolecular photoswitches based on
      ammonioalkyl derivatives of crown ether styryl dyes.
AB  - The synthesis of new styryl dyes derived from 4-pyridine and 4-quinoline and
      having an ammonioalkyl N-substituent and benzocrown ether moieties of different
      sizes and with different sets of heteroatoms was developed. Spontaneous "head-to
      tail" dimerization of these dyes via the formation of numerous hydrogen bonds
      between the terminal NH3(+) groups and crown ether moieties was detected in MeCN
      solutions. The stability constants of the dimeric complexes having pseudocyclic
      structure were studied by (1)H NMR titration. The most stable complexes (log Kd
      up to 8.2) were found in the case of dyes with the 18-crown-6 ether moiety, which
      is most complementary for binding a primary ammonium group. Stacking interaction
      of the conjugated systems in the dimeric complexes contributes to their stability
      to a much lesser extent. In dimeric complexes, the ethylene bonds of the dyes are
      preorganized for stereospecific [2 + 2] photocycloaddition (PCA) induced by
      visible light. PCA yields only rctt isomers of bis-crown-containing cyclobutane
      derivatives. The dyes were studied by X-ray diffraction; it was found that the
      dimeric arrangement is also retained in the crystalline state. The possibility of
      topochemical PCA of the dyes in single crystals without their destruction was
      demonstrated. The possibility of retro-PCA of the obtained cyclobutane
      derivatives to give the starting dyes was shown. The elucidated regularities of
      PCA can be used to fabricate optical data recording systems based on ammonioalkyl
      derivatives of crown ether styryl dyes. 

PMID- 25387103
TI  - Wound drainage following groin dissection for malignant disease in adults.
AB  - BACKGROUND: Groin dissection is commonly performed for the treatment of a variety
      of cancers, including melanoma, and squamous cell carcinoma of the skin, penis or
      vulva. It is uncertain whether insertion of a drain reduces complication rates,
      and, if used, the optimum time for drain removal after surgery is also unknown.
      OBJECTIVES: To assess the current level of evidence to determine whether
      placement of a drain is beneficial after groin dissection in terms of reducing
      seroma, haematoma, wound dehiscence and wound infection rates, and to determine
      the optimal type and duration of drainage following groin dissection if it is
      shown to be beneficial. SEARCH METHODS: In September 2014 we searched the
      following electronic databases using a pre-designed search strategy: the Cochrane
      Wounds Group Specialised Register; The Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library). In November 2013 we searched Ovid
      MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and
      EBSCO CINAHL. We did not restrict the search and study selection with respect to
      language, date of publication or study setting. SELECTION CRITERIA: We considered
      all randomised controlled trials (RCTs) comparing wound drainage with no wound
      drainage in individuals undergoing groin dissection, where the most superior node
      excised was Cloquet's node (the most superior inguinal lymph node). No limits
      were applied to language of publication or trial location. Two review authors
      independently determined the eligibility of each trial. DATA COLLECTION AND
      ANALYSIS: Two review authors, working independently, screened studies identified
      from the search; there were no disagreements. MAIN RESULTS: We did not identify
      any RCTs that met the inclusion criteria for the review. AUTHORS' CONCLUSIONS:
      There is a need for high quality RCTs to guide clinical practice in this under
      researched area.

PMID- 25387104
TI  - The effect of antibiotics on associated bacterial community of stored product
      mites.
AB  - BACKGROUND: Bacteria are associated with the gut, fat bodies and reproductive
      organs of stored product mites (Acari: Astigmata). The mites are pests due to the
      production of allergens. Addition of antibiotics to diets can help to
      characterize the association between mites and bacteria. METHODOLOGY AND
      PRINCIPAL FINDINGS: Ampicillin, neomycin and streptomycin were added to the diets
      of mites and the effects on mite population growth (Acarus siro, Lepidoglyphus
      destructor and Tyrophagus putrescentiae) and associated bacterial community
      structure were assessed. Mites were treated by antibiotic supplementation (1 mg
      g(-1) of diet) for 21 days and numbers of mites and bacterial communities were
      analyzed and compared to the untreated control. Bacterial quantities, determined
      by real-time PCR, significantly decreased in antibiotic treated specimens from 5
      to 30 times in A. siro and T. putrescentiae, while no decline was observed in L.
      destructor. Streptomycin treatment eliminated Bartonella-like bacteria in the
      both A. siro and T. putrescentiae and Cardinium in T. putrescentiae. Solitalea
      like bacteria proportion increased in the communities of neomycin and
      streptomycin treated A. siro specimens. Kocuria proportion increased in the
      bacterial communities of ampicillin and streptomycin treated A. siro and neomycin
      and streptomycin treated L. destructor. CONCLUSIONS/SIGNIFICANCE: The work
      demonstrated the changes of mite associated bacterial community under antibiotic
      pressure in pests of medical importance. Pre-treatment of mites by 1 mg g(-1)
      antibiotic diets improved mite fitness as indicated accelerated population growth
      of A. siro pretreated streptomycin and neomycin and L. destructor pretreated by
      neomycin. All tested antibiotics supplemented to diets caused the decrease of
      mite growth rate in comparison to the control diet.

PMID- 25387105
TI  - Cervical cancer screening among university students in South Africa: a theory
      based study.
AB  - INTRODUCTION: Cervical cancer is a serious public health problem in South Africa.
      Even though the screening is free in health facilities in South Africa, the Pap
      smear uptake is very low. The objective of the study is to investigate the
      knowledge and beliefs of female university students in South Africa. METHODS: A
      cross sectional study was conducted among university women in South Africa to
      elicit information about knowledge and beliefs, and screening history. RESULTS: A
      total of 440 students completed the questionnaire. The average age of the
      participants was 20.39 years (SD  = 1.71 years). Regarding cervical cancer, 55.2%
      (n = 243) had ever heard about it. Results indicated that only 15% (22/147) of
      the students who had ever had sex and had heard about cervical cancer had taken a
      Pap test. Pearson correlation analysis showed that cervical cancer knowledge had
      a significantly negative relationship with barriers to cervical cancer screening.
      Susceptibility and seriousness score were significantly moderately correlated
      with benefit and motivation score as well as barrier score. Self-efficacy score
      also had a moderate correlation with benefit and motivation score. Students who
      had had a Pap test showed a significantly lower score in barriers to being
      screened compared to students who had not had a Pap test. CONCLUSION: This study
      showed that educated women in South Africa lack complete information on cervical
      cancer. Students who had had a Pap test had significantly lower barriers to
      cervical cancer screening than those students who had not had a Pap test.

PMID- 25387106
TI  - Production of phytotoxic cationic alpha-helical antimicrobial peptides in plant
      cells using inducible promoters.
AB  - Synthetic linear antimicrobial peptides with cationic alpha-helical structures,
      such as BP100, have potent and specific activities against economically important
      plant pathogenic bacteria. They are also recognized as valuable therapeutics and
      preservatives. However, highly active BP100 derivatives are often phytotoxic when
      expressed at high levels as recombinant peptides in plants. Here we demonstrate
      that production of recombinant phytotoxic peptides in transgenic plants is
      possible by strictly limiting transgene expression to certain tissues and
      conditions, and specifically that minimization of this expression during
      transformation and regeneration of transgenic plants is essential to obtain
      viable plant biofactories. On the basis of whole-genome transcriptomic data
      available online, we identified the Os.hsp82 promoter that fulfilled this
      requirement and was highly induced in response to heat shock. Using this
      strategy, we generated transgenic rice lines producing moderate yields of
      severely phytotoxic BP100 derivatives on exposure to high temperature. In
      addition, a threshold for gene expression in selected tissues and stages was
      experimentally established, below which the corresponding promoters should be
      suitable for driving the expression of recombinant phytotoxic proteins in
      genetically modified plants. In view of the growing transcriptomics data
      available, this approach is of interest to assist promoter selection for specific
      purposes. 

PMID- 25387108
TI  - Thermal biology of domestic animals.
AB  - The thermal environment is the most important ecological factor determining the
      growth, development, and productivity of domestic animals. Routes of energy
      exchange (sensible heat and latent heat) between animals and their environment
      are greatly influenced by body weight, fat deposition, hair-coat properties,
      functional activity, and number of sweat glands, as well as the presence or
      absence of anatomical respiratory countercurrent heat exchange capability.
      Differences in these anatomical features across species have led to
      specialization of heat exchange. Thermal plasticity and degree of acclimation are
      critical factors determining the ability of animals to respond to environmental
      change. Increases in productive capability of domestic animals can compromise
      thermal acclimation and plasticity, requiring greater investments in housing
      systems that reduce variability of the thermal environment. The combination of
      steadily increasing metabolic heat production as domestic animal productivity
      increases and a rising world temperature poses ongoing and future challenges to
      maintaining health and well-being of domestic animals. 

PMID- 25387109
TI  - The early impact of genomics and metagenomics on ruminal microbiology.
AB  - Knowledge gained from early and recent studies that define the functions of
      microbial populations within the rumen microbiome is essential to allow for
      directed rumen manipulation strategies. A large number of omic studies have
      focused on carbohydrate active enzymes either for improved fiber digestion within
      the animal or for use in industries such as biofuels. Studies of the rumen
      microbiome with respect to methane production and abatement strategies have led
      to initiatives for defining the microbiome of low- and high-methane-emitting
      animals while ensuring optimal feed conversion. With advances in omic
      technologies, the ability to link host genetics and the rumen microbiome by
      studying all the biological components (holobiont) through the use of
      hologenomics has begun. However, a program to culture and isolate microbial
      species for the purpose of standard microbial characterization to aid in
      assigning function to genomic data remains critical, especially for genes of
      unknown function. 

PMID- 25387107
TI  - Chronic ethanol consumption profoundly alters regional brain ceramide and
      sphingomyelin content in rodents.
AB  - Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse
      model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM)
      concentrations from whole brain lipid extracts were measured using electrospray
      mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased
      significantly (range: 25-607%); in juveniles, 6 CER decreased (range: -9 to 
      37%). In contrast, only three SM decreased in adult and one increased
      significantly in juvenile. Next, regional identification at 50 MUm spatial
      resolution from coronal sections was obtained with matrix implanted laser
      desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver
      nanoparticulate matrices followed by focused laser desorption. Most of the CER
      and SM quantified in whole brain extracts were detected in MILDI images. Coronal
      sections from three brain levels show qualitative regional changes in CER-SM ion
      intensities, as a function of group and brain region, in cortex, striatum,
      accumbens, habenula, and hippocampus. Highly correlated changes in certain white
      matter CER-SM pairs occur in regions across all groups, including the hippocampus
      and the lateral (but not medial) cerebellar cortex of adult mice. Our data
      provide the first microscale MS evidence of regional lipid intensity variations
      induced by alcohol. 

PMID- 25387110
TI  - Comparative dendritic cell biology of veterinary mammals.
AB  - Dendritic cells (DC) have a main function in innate immunity in that they sense
      infections and environmental antigens at the skin and mucosal surfaces and
      thereby critically influence decisions about immune activation or tolerance. As
      professional antigen-presenting cells, they are essential for induction of
      adaptive immune responses. Consequently, knowledge on this cell type is required
      to understand the immune systems of veterinary mammals, including cattle, sheep,
      pigs, dogs, cats, and horses. Recent ontogenic studies define bona fide DC as an
      independent lineage of hematopoietic cells originating from a common precursor.
      Distinct transcription factors control the development into the two subsets of
      classical DC and plasmacytoid DC. These DC subsets express a distinguishable
      transcriptome, which differs from that of monocyte-derived DC. Using a
      comparative approach based on phenotype and function, this review attempts to
      classify DC of veterinary mammals and to describe important knowledge gaps. 

PMID- 25387111
TI  - Strategies for design and application of enteric viral vaccines.
AB  - Enteric viral infections in domestic animals cause significant economic losses.
      The recent emergence of virulent enteric coronaviruses [porcine epidemic diarrhea
      virus (PEDV)] in North America and Asia, for which no vaccines are available,
      remains a challenge for the global swine industry. Vaccination strategies against
      rotavirus and coronavirus (transmissible gastroenteritis virus) infections are
      reviewed. These vaccination principles are applicable against emerging enteric
      infections such as PEDV. Maternal vaccines to induce lactogenic immunity, and
      their transmission to suckling neonates via colostrum and milk, are critical for
      early passive protection. Subsequently, in weaned animals, oral vaccines
      incorporating novel mucosal adjuvants (e.g., vitamin A, probiotics) may provide
      active protection when maternal immunity wanes. Understanding intestinal and
      systemic immune responses to experimental rotavirus and transmissible
      gastroenteritis virus vaccines and infection in pigs provides a basis and model
      for the development of safe and effective vaccines for young animals and children
      against established and emerging enteric infections. 

PMID- 25387112
TI  - Chronic wasting disease of cervids: current knowledge and future perspectives.
AB  - A naturally occurring transmissible spongiform encephalopathy (TSE) of mule deer
      was first reported in Colorado and Wyoming in 1967 and has since spread to other
      members of the cervid family in 22 states, 2 Canadian provinces, and the Republic
      of Korea. Chronic wasting disease (CWD), caused by exposure to an abnormally
      folded isoform of the cellular prion protein, is characterized by progressive
      neurological disease in susceptible natural and experimental hosts and is
      ultimately fatal. CWD is thought to be transmitted horizontally in excreta and
      through contaminated environments, features common to scrapie of sheep, though
      rare among TSEs. Evolving detection methods have revealed multiple strains of CWD
      and with continued development may lead to an effective antemortem test. Managing
      the spread of CWD, through the development of a vaccine or environmental cleanup
      strategies, is an active area of interest. As such, CWD represents a unique
      challenge in the study of prion diseases. 

PMID- 25387113
TI  - Uterine responses to the preattachment embryo in domestic ungulates: recognition
      of pregnancy and preparation for implantation.
AB  - The endometrium is a tissue newly evolved with the development of mammalian
      species. Its main function is the support of embryonic growth and development and
      the nutrition of the fetus. The species-specific differences in establishment and
      maintenance of pregnancy make the study of this tissue in various mammalian
      organisms particularly interesting. With the application of omics technologies to
      various mammalian species, many systematic studies of endometrial gene expression
      changes during the phase of establishment of pregnancy have been performed to
      obtain a global view of regulatory events associated with this biological
      process. This review summarizes the results of trancriptome studies of bovine,
      porcine, and equine endometrium. Furthermore, the results are compared between
      these species and to humans. Because an increasing number of studies suggest an
      important role of small regulatory RNAs (i.e., microRNAs), recent findings
      related to the regulation of endometrial functions and the development of the
      conceptus are presented. 

PMID- 25387114
TI  - The genetics of skeletal muscle disorders in horses.
AB  - Horses are remarkable athletes and a fascinating species in which to study the
      genetic bases of athletic performance, skeletal muscle biology, and neuromuscular
      disease. Genetic selection in horses has resulted in many breeds that possess
      anatomical, physiological, and metabolic variations linked to speed, power, and
      endurance that are beginning to be defined at the molecular level. Along with the
      concentration of positive traits, equine breeding programs have also
      inadvertently concentrated heritable muscle diseases for which mutations
      impacting electrical conduction, muscle contraction, and energy metabolism within
      and across breeds have been characterized. The study of heritable muscle diseases
      in horses has provided exciting insights into the normal structure and function
      of muscle and important diagnostic tools for veterinarians. Results empower
      breeders and breed associations to make difficult decisions about how to use this
      information to improve the overall health and well-being of horses. 

PMID- 25387115
TI  - The domestic piglet: an important model for investigating the neurodevelopmental
      consequences of early life insults.
AB  - Insults in the prenatal and early postnatal period increase the risk for
      behavioral problems later in life. One hypothesis is that pre- and postnatal
      stressors influence structural and functional brain plasticity. Understanding the
      mechanisms is important, but progress has lagged because certain studies in human
      infants are impossible, while others are extremely difficult. Furthermore,
      results from popular rodent models are difficult to translate to human infants
      owing to the substantial differences in brain development and morphology. Because
      it overcomes some of these obstacles, the domestic piglet has emerged as an
      important model. Piglets have a gyrencephalic brain that develops similar to the
      human brain and that can be assessed in vivo by using clinical-grade neuroimaging
      instruments. Furthermore, owing to their precocial nature, piglets can be weaned
      at birth and used in behavioral testing paradigms to assess cognitive behavior at
      an early age. Thus, the domestic piglet represents an important translational
      model for investigating the neurodevelopmental consequences of early life
      insults. 

PMID- 25387116
TI  - A new medical research model: ethically and responsibly advancing health for
      humans and animals.
AB  - With the increasing use of genomics, computational analytics, emerging
      technologies, and personalized medicine, the possibility of a new research model
      is emerging. Using the clues from thousands of species living on our planet,
      scientists from many disciplines (medicine, veterinary medicine, wildlife) must
      collaborate, prioritize, and strategize on how to address causes of health and
      disease. Such clues should guide disease prevention, as well as the development
      of innovative, efficacious, and gentler therapies. Geographic and language
      barriers must be broken down, and scientists--even within a single academic,
      corporate, or government research site--must be vigilant in seeking the help of
      nonmedical disciplines of colleagues from whence answers might come. The public
      will become more interested in and demanding of such a model, desiring that all
      family members (humans and animals) have an opportunity for a long and healthy
      life. Above all, such activities will be humanely conducted with outcomes having
      the greatest chance for success.

PMID- 25387117
TI  - Genetically engineered livestock: ethical use for food and medical models.
AB  - Recent advances in the production of genetically engineered (GE) livestock have
      resulted in a variety of new transgenic animals with desirable production and
      composition changes. GE animals have been generated to improve growth efficiency,
      food composition, and disease resistance in domesticated livestock species. GE
      animals are also used to produce pharmaceuticals and as medical models for human
      diseases. The potential use of these food animals for human consumption has
      prompted an intense debate about food safety and animal welfare concerns with the
      GE approach. Additionally, public perception and ethical concerns about their use
      have caused delays in establishing a clear and efficient regulatory approval
      process. Ethically, there are far-reaching implications of not using genetically
      engineered livestock, at a detriment to both producers and consumers, as use of
      this technology can improve both human and animal health and welfare. 

PMID- 25387118
TI  - Potentiometric response from ion-selective nanospheres with voltage-sensitive
      dyes.
AB  - Potentiometric sensors require the implementation of conducting wires for signal
      transduction, but this is impractical for the readout of individual
      nanoparticles. It is here demonstrated for the first time that the potentiometric
      response of ion-selective nanospheres can be observed with voltage-sensitive
      dyes, thereby converting nanoscale electrochemical signals into an optical
      readout. No reference electrode is needed since the readout is by fluorescence.
      The results strongly support the potentiometric origin for the fluorescence
      response. The ion-selective nanospheres exhibit excellent selectivity and respond
      to ion concentration changes independent of sample pH, providing a new platform
      of potentiometric nanosensors with optical readout compatible with optical
      imaging equipment. 

PMID- 25387119
TI  - Radioligand imaging of alpha4beta2* nicotinic acetylcholine receptors in
      Alzheimer's disease and Parkinson's disease.
AB  - The alpha4beta2* nicotinic acetylcholine receptors (alpha4beta2*-nAChR) are
      highly abundant in the human brain. As neuromodulators they play an important
      role in cognitive functions such as memory, learning and attention as well as
      mood and motor function. Post mortem studies suggest that abnormalities of
      alpha4beta2*-nAChRs are closely linked to histopathological hallmarks of
      Alzheimer's disease (AD), such as amyloid aggregates/oligomers and tangle
      pathology and of Parkinson's disease (PD) such as Lewy body pathology and the
      nigrostriatal dopaminergic deficit. In this review we summarize and discuss
      nicotinic receptor imaging findings of 2-[18F]FA-85380 PET, [11C]nicotine PET and
      5-[123I]IA-85380 SPECT studies investigating alpha4beta2*-nAChR binding in vivo
      and their relationship to mental dysfunction in the brain of patients with AD and
      patients out of the spectrum of Lewy body disorders such as PD and Lewy body
      dementia (DLB). Furthermore, recent developments of novel alpha4beta2*-nAChR
      specific PET radioligands, such as (-)[18F]Flubatine or [18F]AZAN are summarized.
      We conclude that alpha4beta2*-nAChR-specific PET might become a biomarker for
      early diagnostics and drug developments in patients with AD, DLB and PD, even at
      early or prodromal stages. 

PMID- 25387122
TI  - The Contribution of Youth Sport Football to Weekend Physical Activity for Males
      Aged 9 to 16 Years: Variability Related to Age and Playing Position.
AB  - The aims of this study were (1) to determine minutes of moderate-to-vigorous
      physical activity (PA) and vigorous PA accrued in youth sport football (also
      internationally referred to as soccer), and the contribution toward daily weekend
      moderate-to-vigorous PA and vigorous PA for males aged 9-16 years, and (2) to
      investigate variability in these outcomes related to age and playing position.
      One hundred and nine male grassroots footballers (Mean age = 11.98 +/- 1.75
      years) wore a GT3* accelerometer for 7 days. Weekend youth sport football
      participation and playing position were recorded. Youth sport football moderate
      to-vigorous PA (M = 51.51 +/- 17.99) and vigorous PA (M = 27.78 +/- 14.55)
      contributed 60.27% and 70.68% toward daily weekend moderate-to-vigorous PA and
      vigorous PA, respectively. Overall, 36.70% of participants accumulated >=60 min
      moderate-to-vigorous PA and 69.70% accrued >= 20 min of vigorous PA during youth
      sport. For participants aged 13 to16 years, youth sport football moderate-to
      vigorous PA and vigorous PA were significantly higher, and contributed a greater
      amount toward daily weekend moderate-to-vigorous PA and vigorous PA than for
      participants aged 9-12 years (p = <.01). Youth sport football is an important
      source of moderate-to-vigorous PA and vigorous PA at the weekend for male youth,
      and particularly for adolescents. Participation may offer opportunity for weekend
      engagement in vigorous PA toward health enhancing levels. 

PMID- 25387123
TI  - Effectiveness and feasibility of laparoscopic distal pancreatectomy on patients
      at high anesthetic risk.
AB  - BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is the most acceptable
      procedure in laparoscopic pancreatic surgery. Nevertheless, knowledge regarding
      patients at a high anesthetic risk during lengthy and technically demanding LDP
      is controversial. This study aims to assess the feasibility and safety of LDP in
      patients with high anesthetic risk. PATIENTS AND METHODS: We conducted a
      prospective collection retrospective review of patients underwent LDP and open
      distal pancreatectomy (ODP) from January 2011 until December 2013. By the
      American Society of Anesthesiologists score, patients were divided into low- and
      high-risk patients. We compared the clinical, perioperative, and postoperative
      results in these patients. RESULTS: The cohort included 77 patients: 20 underwent
      LDP, and 57 underwent ODP. There were 30 patients in the low-risk group and 47
      patients in the high-risk group. In high-risk patients, LDP, compared with ODP,
      presented a shorter operating time (mean, 220.8+/-101.1 minutes versus 299.4+/
      124.3 minutes; P=.038), less blood loss (409.3+/-569.9 mL versus 1083.1+/-1583.0
      mL; P=.039), higher rate of spleen preservation (73.3% versus 43.8%, P=.037), and
      shorter length of postoperative hospital stay (LOS) (9.5+/-3.0 days versus 15.7+/
      9.4 days; P=.044). CONCLUSIONS: In conclusion, LDP provides early recovery and
      better cosmetic appearance. In high anesthetic risk patients, LDP shows less
      operative time, less perioperative blood loss, a higher rate of spleen
      preservation, slighter complication, and shorter LOS, which might explain why LDP
      is a feasible and effective procedure.

PMID- 25387124
TI  - Low transition temperature mixtures as innovative and sustainable CO2 capture
      solvents.
AB  - The potential of three newly discovered low transition temperature mixtures
      (LTTMs) is explored as sustainable substituents for the traditional carbon
      dioxide (CO2) absorbents. LTTMs are mixtures of two solid compounds, a hydrogen
      bond donor (HBD) and a hydrogen bond acceptor (HBA), which form liquids upon
      mixing with melting points far below those of the individual compounds. In this
      work the HBD is lactic acid and the HBAs are tetramethylammonium chloride,
      tetraethylammonium chloride, and tetrabutylammonium chloride. These compounds
      were found to form LTTMs for the first time at molar ratios of HBD:HBA = 2:1.
      First, the LTTMs were characterized by determining the thermal operating window
      (e.g., decomposition temperature and glass transition temperature) and the
      physical properties (e.g., density and viscosity). Thereafter, the phase behavior
      of CO2 with the LTTMs has been measured using a gravimetric magnetic suspension
      balance operating in the static mode at 308 and 318 K and pressures up to 2 MPa.
      The CO2 solubility increased with increasing chain length, increasing pressure,
      and decreasing temperature. The Peng-Robinson equation of state was applied to
      correlate the phase equilibria. From the solubility data, thermodynamic
      parameters were determined (e.g., Henry's law coefficient and enthalpy of
      absorption). The heat of absorption was found to be similar to that in
      conventional physical solvents (-11.21 to -14.87 kJ.mol(-1)). Furthermore, the
      kinetics in terms of the diffusion coefficient of CO2 in all LTTMs were
      determined (10(-11)-10(-10) m(2).s(-1)). Even though the CO2 solubilities in the
      studied LTTMs were found to be slightly lower than those in thoroughly studied
      conventional physical solvents, LTTMs are a promising new class of absorbents due
      to their low cost, their environmentally friendly character, and their easy
      tunability, allowing further optimization for carbon capture. 

PMID- 25387125
TI  - Smooth change, mechanistic fluctuation: thermodynamic system drift in protein
      evolution.

PMID- 25387126
TI  - High-performers use the phonological loop less to process mental arithmetic
      during working memory tasks.
AB  - This study investigated the effects of three working memory components-the
      central executive, phonological loop, and visuospatial sketchpad-on performance
      differences in complex mental arithmetic between individuals. Using the dual-task
      method, we examined how performance during two-digit addition was affected by
      load on the central executive (random tapping condition), phonological loop
      (articulatory suppression condition), and visuospatial sketchpad (spatial tapping
      condition) compared to that under no load (control condition) in high- and low
      performers of complex mental arithmetic in Experiment 1. Low-performers showed an
      increase in errors under the random tapping and articulatory suppression
      conditions, whereas high-performers showed an increase of errors only under the
      random tapping condition. In Experiment 2, we conducted similar experiments on
      only the high-performers but used a shorter presentation time of each number. We
      found the same pattern for performing complex mental arithmetic as seen in
      Experiment 1. These results indicate that high-performers might reduce their
      dependence on the phonological loop, because the central executive enables them
      to choose a strategy in which they use less working memory capacity. 

PMID- 25387127
TI  - Acute Consumption of an Energy Drink Does Not Improve Physical Performance of
      Female Volleyball Players.
AB  - To determine the acute effect of an energy drink (ED) on physical performance of
      professional female volleyball players. 19 females (age= 22.3 +/- 4.9 yr.;
      height= 171.8 +/- 9.4 cm; weight= 65.2 +/- 10.1 kg) participated in a randomized,
      crossover, double-blind study to measure grip strength, vertical jump and
      anaerobic power in 3 different sessions (ED, placebo [PL] or no beverage [CTL]).
      For each session, participants arrived in a fasted state, consumed a standardized
      breakfast meal, and 1 hr later completed the 3 baseline performance tests without
      having ingested the beverage. After completing the premeasurements, the athletes
      drank 6 ml/kg of body weight of the ED or PL and in the CTL condition no beverage
      was consumed. Posttest measurements were taken 30 min after the ingestion of
      liquids. A 3 * 2 repeated-measures ANOVA revealed no significant within-session
      and measurement time interactions for each performance test. Regardless of the
      measurement time, right hand grip strength was significantly higher in the ED
      condition (34.6 +/- 0.9 kg) compared with PL (33.4 +/- 1.1 kg) and CTL (33.6 +/-
      1.0 kg) (p < 0.05). Regardless of the beverage ingested, averaged right hand grip
      strength, taking into account all 3 testing conditions, increased from pre to
      posttesting (Pre = 33.8 +/- 0.9 kg vs. Post = 33.9 +/- 1.0 kg; p = 0.029), as did
      the averaged fatigue index, obtained from the anaerobic power test (Pre = 65.9+/-
      2.2% vs. Post = 68.7+/- 2.0%; p= 0.049). The acute ingestion of an ED did not
      improve physical performance of professional Costa Rican female volleyball
      players. 

PMID- 25387129
TI  - Putative transmembrane domain 6 of the human organic anion transporting
      polypeptide 1A2 (OATP1A2) influences transporter substrate binding, protein
      trafficking, and quality control.
AB  - The human organic anion transporting polypeptides (OATPs) are a family of
      important membrane proteins that mediate the cellular influx of various anionic
      substances including clinically important drugs. Transmembrane domain 6 (TM6) is
      a distinctive consensus "signature" common to all OATPs. Two naturally occurring
      variants were previously identified in TM6 of the important transporter OATP1A2;
      these variants may be associated with suboptimal drug influx into cells. Because
      of the potential importance of TM6 in drug efficacy, this study investigated its
      role in substrate uptake by OATP1A2. Single amino acid replacements were
      introduced into TM6 of OATP1A2 (residues 245-266) by alanine-scanning
      mutagenesis. Uptake assays, biotinylation and immunoblotting were used to assess
      the function and expression of OATP1A2 and its mutants after overexpression in
      HEK293 cells. Uptake of the model substrates estrone-3-sulfate and methotrexate
      by OATP1A2 mutants carrying amino acid replacements within the TM6 subregions of
      245-248 and 261-266 was impaired, while transport function was largely retained
      by other mutants. From kinetic, biotinylation, and immunoblot analysis the
      diminished function of the 245-248 and 261-266 mutants was due primarily to
      decreased plasma membrane and total cell expression and also to a less extent,
      impacted by altered substrate binding. Further experiments with proteasomal or
      lysosomal inhibitors were consistent with impaired maturation and impaired plasma
      membrane insertion of several mutants of OATP1A2 within the subregions of 245-248
      and 261-266. In addition, the finding that total cellular expression, but not
      plasma membrane expression, was less impaired for the W245A and W246A mutants
      suggests that these two TM6 residues might be involved in membrane targeting of
      OATP1A2. These findings implicate the TM6 subregions of 245-248 and 261-266 in
      substrate binding, protein trafficking, and quality control of OATP1A2. 

PMID- 25387128
TI  - N-terminal cleavage and release of the ectodomain of Flt1 is mediated via ADAM10
      and ADAM 17 and regulated by VEGFR2 and the Flt1 intracellular domain.
AB  - Flt is one of the cell surface VEGF receptors which can be cleaved to release an
      N-terminal extracellular fragment which, like alternately transcribed soluble
      Flt1 (sFlt1), can antagonize the effects of VEGF. In HUVEC and in HEK293 cells
      where Flt1 was expressed, metalloprotease inhibitors reduced Flt1 N-terminal
      cleavage. Overexpression of ADAM10 and ADAM17 increased cleavage while knockdown
      of ADAM10 and ADAM17 reduced N-terminal cleavage suggesting that these
      metalloproteases were responsible for Flt1 cleavage. Protein kinase C (PKC)
      activation increased the abundance and the cleavage of Flt1 but this did not
      require any residues within the intracellular portion of Flt1. ALLN, a
      proteasomal inhibitor, increased the abundance of Flt1 which was additive to the
      effect of PKC. Removal of the entire cytosolic region of Flt1 appeared to
      stimulate cleavage of Flt1 and Flt1 was no longer sensitive to ALLN suggesting
      that the cytosolic region contained a degradation domain. Knock down of c-CBL, a
      ring finger ubiquitin ligase, in HEK293 cells increased the expression of Flt1
      although it did not appear to require a previously published tyrosine residue
      (1333Y) in the C-terminus of Flt1. Increasing VEGFR2 expression increased VEGF
      stimulated sFlt1 expression and progressively reduced the cleavage of Flt1 with
      Flt1 staying bound to VEGFR2 as a heterodimer. Our results imply that secreted
      sFlt1 and cleaved Flt1 will tend to have local effects as a VEGF antagonist when
      released from cells expressing VEGFR2 and more distant effects when released from
      cells lacking VEGFR2. 

PMID- 25387130
TI  - Species differences and substrate specificity of CYP3A heteroactivation by
      efavirenz.
AB  - 1. The purpose of this study was to clarify species differences in the
      heteroactivation of CYP3A substrates by efavirenz, which is known from clinical
      studies to activate midazolam 1'-hydroxylation, and to assess the feasibility of
      an animal model. 2. In monkey and human liver microsomes, efavirenz activated
      CYP3A-mediated midazolam 1'-hydroxylation, but had no effect in rat liver
      microsomes. The activating effect of efavirenz was also observed with recombinant
      human CYP3A4 and CYP3A5. Midazolam 4-hydroxylation, testosterone 6beta
      hydroxylation and the oxidation of nifedipine were not activated by efavirenz in
      any of the microsomes. 3. In an in vivo study using monkeys, the AUC ratio of
      midazolam/1'-hydroxymidazolam was reduced from 0.85 to 0.30 by efavirenz
      treatment, which was comparable to that obtained in clinical studies. However,
      the AUC changes of midazolam caused by efavirenz were smaller than those observed
      in clinical results, therefore the effect of efavirenz on monkeys was not
      completely consistent with that seen in humans. 4. In conclusion, this is the
      first report that efavirenz specifically activates midazolam 1'-hydroxylation
      only in monkey and human liver microsomes, revealing marked species differences
      and high substrate specificity in the heteroactivation. A further study is
      required to clarify whether this in vitro result reflects the in vivo situation. 

PMID- 25387131
TI  - High aspect ratio PS-b-PMMA block copolymer masks for lithographic applications.
AB  - The control of the self-assembly (SA) process and nanostructure orientation in
      diblock copolymer (DBC) thick films is a crucial technological issue.
      Perpendicular orientation of the nanostructures in symmetric and asymmetric
      poly(styrene)-b-poly(methyl methacrylate) (PS-b-PMMA) block copolymer films
      obtained by means of simple thermal treatments was demonstrated to occur in well
      defined thickness windows featuring modest maximum values, thus resulting in low
      aspect ratio (h/d < 2) of the final lithographic mask. In this manuscript, the
      thickness window corresponding to the perpendicular orientation of the
      cylindrical structures in asymmetric DBC is investigated at high temperatures
      (190  degrees C <= T <= 310  degrees C) using a rapid thermal processing machine.
      A systematic study of the annealing conditions (temperature and time) of
      asymmetric PS-b-PMMA (Mn = 67.1, polydispersity index = 1.09) films, with
      thicknesses ranging from 10 to 400 nm, allowed ordered patterns, with a maximum
      value of orientational correlation length of 350 nm, to be obtained for film
      thicknesses up to 200 nm. The complete propagation of the cylindrical structures
      through the whole film thickness in a high aspect ratio PS template (h/d ~ 7) is
      probed by lift-off process. Si nanopillars are obtained having the same lateral
      ordering and characteristic dimensions of the DBC lithographic mask as further
      confirmed by grazing-incidence small-angle X-ray scattering experiments.

PMID- 25387132
TI  - Cys(i)-Lys(i+3)-Lys(i+4) triad: a general approach for PEG-based stabilization of
      alpha-helical proteins.
AB  - PEGylation is an important strategy for enhancing the pharmacokinetic properties
      of protein drugs. Modern chemoselective reactions now enable specific placement
      of a single PEG at any site on a protein surface. However, few rational structure
      based guidelines exist for selecting optimal PEGylation sites. Here, we explore
      the impact of PEGylation on the conformational stability of alpha-helices using
      an alpha-helical coiled coil as a model system. We find that maleimide-based
      PEGylation of a solvent-exposed i position Cys can stabilize coiled-coil
      quaternary structure when Lys residues occupy both the i + 3 and i + 4 positions,
      due to favorable interactions between the PEG-maleimide and the Lys residues.
      Applying this Cys(i)-Lys(i+3)-Lys(i+4) triad to a solvent-exposed position within
      the C-terminal helix of the villin headpiece domain leads to similar PEG-based
      increases in conformational stability, highlighting the possibility of using the
      Cys(i)-Lys(i+3)-Lys(i+4) triad as a general strategy for PEG-based stabilization
      of helical proteins.

PMID- 25387133
TI  - Exopolysaccharide production in response to medium acidification is correlated
      with an increase in competition for nodule occupancy.
AB  - Sinorhizobium meliloti strains unable to utilize galactose as a sole carbon
      source, due to mutations in the De-Ley Doudoroff pathway (dgoK), were previously
      shown to be more competitive for nodule occupancy. In this work, we show that
      strains carrying this mutation have galactose-dependent exopolysaccharide (EPS)
      phenotypes that were manifested as aberrant Calcofluor staining as well as
      decreased mucoidy when in an expR(+) genetic background. The aberrant Calcofluor
      staining was correlated with changes in the pH of the growth medium. Strains
      carrying dgoK mutations were subsequently demonstrated to show earlier
      acidification of their growth medium that was correlated with an increase
      expression of genes associated with succinoglycan biosynthesis as well as
      increased accumulation of high and low molecular weight EPS in the medium. In
      addition, it was shown that the acidification of the medium was dependent on the
      inability of S. meliloti strains to initiate the catabolism of galactose. To more
      fully understand why strains carrying the dgoK allele were more competitive for
      nodule occupancy, early nodulation phenotypes were investigated. It was found
      that strains carrying the dgoK allele had a faster rate of nodulation. In
      addition, nodule competition experiments using genetic backgrounds unable to
      synthesize either succinoglycan or EPSII were consistent with the hypothesis that
      the increased competition phenotype was dependent upon the synthesis of
      succinoglycan. Fluorescent microscopy experiments on infected root-hair cells,
      using the acidotropic dye Lysotracker Red DND-99, provide evidence that the
      colonized curled root hair is an acidic compartment.

PMID- 25387134
TI  - Potato virus Y HCPro localization at distinct, dynamically related and
      environment-influenced structures in the cell cytoplasm.
AB  - Potyvirus HCPro is a multifunctional protein that, among other functions,
      interferes with antiviral defenses in plants and mediates viral transmission by
      aphid vectors. We have visualized in vivo the subcellular distribution and
      dynamics of HCPro from Potato virus Y and its homodimers, using green, yellow,
      and red fluorescent protein tags or their split parts, while assessing their
      biological activities. Confocal microscopy revealed a pattern of even
      distribution of fluorescence throughout the cytoplasm, common to all these
      modified HCPros, when transiently expressed in Nicotiana benthamiana epidermal
      cells in virus-free systems. However, in some cells, distinct additional
      patterns, specific to some constructs and influenced by environmental conditions,
      were observed: i) a small number of large, amorphous cytoplasm inclusions that
      contained alpha-tubulin; ii) a pattern of numerous small, similarly sized, dot
      like inclusions distributing regularly throughout the cytoplasm and associated or
      anchored to the cortical endoplasmic reticulum and the microtubule (MT)
      cytoskeleton; and iii) a pattern that smoothly coated the MT. Furthermore, mixed
      and intermediate forms from the last two patterns were observed, suggesting
      dynamic transports between them. HCPro did not colocalize with actin filaments or
      the Golgi apparatus. Despite its association with MT, this network integrity was
      required neither for HCPro suppression of silencing in agropatch assays nor for
      its mediation of virus transmission by aphids.

PMID- 25387135
TI  - Phytophthora suppressor of RNA silencing 2 is a conserved RxLR effector that
      promotes infection in soybean and Arabidopsis thaliana.
AB  - The genus Phytophthora consists of notorious and emerging pathogens of
      economically important crops. Each Phytophthora genome encodes several hundreds
      of cytoplasmic effectors, which are believed to manipulate plant immune response
      inside the host cells. However, the majority of Phytophthora effectors remain
      functionally uncharacterized. We recently discovered two effectors from the
      soybean stem and root rot pathogen Phytophthora sojae with the activity to
      suppress RNA silencing in plants. These effectors are designated Phytophthora
      suppressor of RNA silencing (PSRs). Here, we report that the P. sojae PSR2
      (PsPSR2) belongs to a conserved and widespread effector family in Phytophthora. A
      PsPSR2-like effector produced by P. infestans (PiPSR2) can also suppress RNA
      silencing in plants and promote Phytophthora infection, suggesting that the PSR2
      family effectors have conserved functions in plant hosts. Using Agrobacterium
      rhizogenes-mediated hairy roots induction, we demonstrated that the expression of
      PsPSR2 rendered hypersusceptibility of soybean to P. sojae. Enhanced
      susceptibility was also observed in PsPSR2-expressing Arabidopsis thaliana plants
      during Phytophthora but not bacterial infection. These experiments provide strong
      evidence that PSR2 is a conserved Phytophthora effector family that performs
      important virulence functions specifically during Phytophthora infection of
      various plant hosts.

PMID- 25387137
TI  - Bioinspired legged-robot based on large deformation of flexible skeleton.
AB  - In this article we present STARbot, a bioinspired legged robot capable of
      multiple locomotion modalities by using large deformation of its skeleton. We
      construct STARbot by using origami-style folding of flexible laminates. The long
      term goal is to provide a robotic platform with maximum mobility on multiple
      surfaces. This paper particularly studies the quasistatic model of STARbot's leg
      under different conditions. We describe the large elastic deformation of a leg
      under external force, payload, and friction by using a set of non-dimensional,
      nonlinear approximate equations. We developed a test mechanism that models the
      motion of a leg in STARbot. We augmented several foot shapes and then tested them
      on soft to rough grounds. Both simulation and experimental findings were in good
      agreement. We utilized the model to develop several scales of tri and quad
      STARbot. We demonstrated the capability of these robots to locomote by combining
      their leg deformations with their foot motions. The combination provided a design
      platform for an active suspension STARbot with controlled foot locomotion. This
      included the ability of STARbot to change size, run over obstacles, walk and
      slide. Furthermore, in this paper we discuss a cost effective manufacturing and
      production method for manufacturing STARbot. 

PMID- 25387143
TI  - Diffuse idiopathic skeletal hyperostosis association with thoracic spine
      kyphosis: a cross-sectional study for the Health Aging and Body Composition
      Study.
AB  - STUDY DESIGN: A descriptive study of the association between diffuse idiopathic
      skeletal hyperostosis (DISH) and kyphosis. OBJECTIVE: To investigate the
      association of DISH with Cobb angle of kyphosis in a large cohort of older
      subjects from the Health Aging and Body Composition Study. SUMMARY OF BACKGROUND
      DATA: DISH and thoracic kyphosis are well-defined radiographical findings in
      spines of older individuals. Characteristics of DISH (ossifications between
      vertebral segments) reflect changes of spine anatomy and physiology that may be
      associated with Cobb angle of kyphosis. METHODS: Using data from 1172 subjects
      aged 70 to 79 years, we measured DISH and Cobb angle of kyphosis from computed
      tomographic lateral scout scans. Characteristics of participants with and without
      DISH were assessed using the chi2 and t tests. Association between DISH and Cobb
      angle was analyzed using linear regression. Cobb angle and DISH relationship was
      assessed at different spine levels (thoracic and lumbar). RESULTS: DISH was
      identified on computed tomographic scout scan in 152 subjects with 101 cases in
      only the thoracic spine and 51 in both thoracic and lumbar spine segments. The
      mean Cobb angle of kyphosis in the analytic sample was 31.3 degrees  (standard
      deviation = 11.2). The presence of DISH was associated with a greater Cobb angle
      of 9.1 degrees  and 95% confidence interval (95% CI) (5.6-12.6) among African
      Americans and a Cobb angle of 2.9 degrees  and 95% CI (0.5-5.2) among Caucasians
      compared with those with no DISH. DISH in the thoracic spine alone was associated
      with a greater Cobb angle of 10.6 degrees  and 95% CI (6.5-14.7) in African
      Americans and a Cobb angle of 3.8 degrees  and 95% CI (1.0-6.5) in Caucasians
      compared with those with no DISH. CONCLUSION: DISH is associated with greater
      Cobb angle of kyphosis, especially when present in the thoracic spine alone. The
      association of DISH with Cobb angle is stronger within the African American
      population.

PMID- 25387144
TI  - How to make the best use of intraoperative motor evoked potential monitoring?
      Experience in 1162 consecutive spinal deformity surgical procedures.
AB  - STUDY DESIGN: A retrospective study of 1162 consecutive patients who underwent
      spinal deformity surgical procedures at our spine center from January 2010 to
      December 2013. OBJECTIVE: To develop and evaluate a protocol of intraoperative
      motor evoked potential (MEP) monitoring with the warning criteria we had
      established on the basis of our clinical experiences and the review of previous
      literature. SUMMARY OF BACKGROUND DATA: Though MEPs monitoring have become widely
      used in spinal deformity surgery, different alarm criteria and response protocol
      used in different studies compromised their comparability; Furthermore, high
      false-positive rate of MEP reported by previous studies has become an
      increasingly prominent problem that will limit its clinical use and development.
      METHODS: The intraoperative monitoring data of 1162 consecutive patients who
      underwent spinal deformity surgical procedures at our spine center were
      retrospectively analyzed. Age, sex, diagnosis, preoperative neurological status,
      intraspinal anomalies, baseline MEP, and MEP change were collected. The protocol
      with the warning criteria we had established was used. The false-positive rate,
      false-negative rate, and positive predictive value were calculated. RESULTS:
      Significant intraoperative changes were seen in the MEP data in 52 (4.4%) of all
      the cases. In 25 cases among which, significant MEP changes were synchronously
      and logically associated with high-risk surgical maneuver (pedicle screw
      insertion, osteotomy, correction, etc.). The false-positive rate of MEP
      monitoring was 0.26% (3/1140), whereas the sensitivity and specificity of MEP for
      detection of clinically significant intraoperative cord injury were 100% and
      99.7%, respectively. The positive predictive value of a MEP alert in terms of a
      new postoperative neurological deficit was 83.3%. CONCLUSION: Our study indicates
      that the appropriate use of MEP monitoring based on our protocol is able to
      obtain satisfying sensitivity and specificity and thus provide important
      information for intraoperative decision making.

PMID- 25387145
TI  - Re : He B, Yan L, Guo H, et al. The difference in superior adjacent segment
      pathology after lumbar posterolateral fusion by using 2 different pedicle screw
      insertion techniques in 9-year minimum follow-up. Spine (Phila Pa 1976)
      2014;39:1093-8.

PMID- 25387146
TI  - Re: Aleksiev AR. Ten-year follow-up of strengthening versus flexibility exercises
      with or without abdominal bracing in recurrent low back pain.

PMID- 25387148
TI  - Urates in exhaled breath condensate as a biomarker of control in childhood
      asthma.
AB  - OBJECTIVE: The aim of this study was to (1) investigate the possibility to use
      urates in exhaled breath condensate (EBC) as a biomarker of airway inflammation
      and control in childhood asthma and (2) explore their association with other
      biomarkers of airway inflammation and clinical indices of asthma control (Asthma
      Control Test [ACT], quality of life [PAQLQ], lung function, prn beta-agonist use,
      time from last exacerbation [TLE]. METHODS: This cross-sectional study comprised
      103 consecutive patients (age 6-18 years) divided in groups of uncontrolled
      ([NC], n = 53) and controlled asthma ([C], n = 50). Measured lung function and
      biomarkers included: spirometry, eosinophilic cationic protein (ECP), high
      sensitivity C-reactive protein (hs-CRP), exhaled NO (FENO), pH and urates in EBC
      and exhaled breath temperature (EBT). RESULTS: Statistically significant
      differences were found between groups for EBC urates, EBC pH and EBT (NC versus
      C: EBC urates, median [IQR], umol/L; 10 [6] versus 45 [29], p < 0.001; EBC pH,
      mean [SD], 7.2 [0.17] versus 7.33 [0.16], p = 0.002; EBT mean [SD],  degrees C;
      34.26 [0.83], versus 33.90 [0.60], p = 0.014). EBC urates showed significant
      association with TLE and FENO (r = 0.518, p < 0.001; r = 0.369, p = 0.007,
      respectively) in NC, and EBC pH (r = 0.351, p < 0.001), FEV1 (r = 0.222, p =
      0.024), ACT (r = 0.654, p < 0.001), PAQLQ (r = 0.686, p < 0.001) and prn
      salbutamol use (r = -0.527, p < 0.001) in all asthmatics. CONCLUSION: In our
      study, EBC urates were found to be the best single predictor of asthma control
      and underlying airway inflammation. Our results provide evidence supporting the
      potential utility to use EBC urates as an additional non-invasive biomarker of
      control in childhood asthma.

PMID- 25387149
TI  - Patterns of aeroallergen sensitization predicting risk for asthma in preschool
      children with atopic dermatitis.
AB  - OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder mostly
      affecting young children. Although several studies aimed to identify the risk
      factors for asthma in AD children, many aspects still need to be clarified. The
      aim of this study was to investigate the possible risk factors for asthma at
      school age in 99 children with early-onset and IgE-mediated AD. METHODS: All
      children performed clinical evaluation and total and specific IgE assay for a
      panel of inhalant and food allergens at two different times (t1 and t2) during
      preschool, and asthma diagnosis was assessed at one follow-up visit (t3) at
      school age. RESULTS: At t3, 39% of children had developed asthma. Of the
      variables compared, the sensitization to more than one class of inhalant
      allergens at t2 (mean age = 30 months) was associated with asthma, with grass (OR
      = 3.24, p = 0.020) and cat sensitization (OR = 2.74, p = 0.043) as independent
      risk factors. CONCLUSIONS: The sensitization pattern of a child with early-onset
      AD, also within the first 2-3 years of life, can reflect his risk to develop
      asthma. Therefore, testing these children for the more common allergens during
      this time frame should be recommended to predict the evolution of atopic
      diseases.

PMID- 25387150
TI  - Effectiveness of a modified open airways curriculum.
AB  - OBJECTIVE: Open Airways for Schools is an asthma education program that has
      proven to be effective in decreasing the number of asthma attacks in children and
      increasing their confidence in self-management. It is taught to 8-11 year olds in
      six 40-min sessions. Due to financial and scheduling constraints, many schools
      have difficulty implementing the program. The Tulsa Health Department created a
      modified version of the program, which is taught in ten 20-min sessions over
      lunch. The same topics are covered in a different order and fewer activities are
      utilized. This study aimed to pilot the effectiveness of the modified program.
      METHODS: In both versions, a pre-questionnaire is given to participating students
      on the first day of the program. At the end of the program, the same
      questionnaire is administered to assess knowledge gained. This is a retrospective
      review comparing pre- and post-questionnaire data from the two versions of the
      program. Descriptive statistics and t-tests were used to compare the results of
      the questionnaires from the modified program to results from the original
      program. RESULTS: Twenty students completed the original curriculum and 45
      completed the modified program. Both versions were found to improve children's
      knowledge of how to manage asthma triggers and symptoms, as well as to improve
      inhaler technique. CONCLUSIONS: The modified curriculum is effective at
      increasing asthma knowledge. Schools may use the modified program as an alternate
      delivery approach to reduce the scheduling burden and to allow more children to
      benefit from the educational program.

PMID- 25387151
TI  - The changing epidemiology of asthma in Shanghai, China.
AB  - OBJECTIVE: To investigate the prevalence of bronchial asthma in Putuo district in
      Shanghai, China. METHODS: Cross-sectional, community-based study was performed
      with random sampling of a district with a population of one million. The subjects
      were residents of the district and six or more years of age. Questionnaire and
      spirometry were completed in all subjects. Asthma was defined as physician
      diagnosed asthma. The results were compared with the asthma study of 40,000
      population completed by the same team in Pudong area of Shanghai in 1997.
      RESULTS: We surveyed 27,042 participants. The prevalence of asthma was 1.8%
      (488/27,042), much higher than the 0.41% (163/40,000) found in the 1997 survey in
      Pudong area of Shanghai. In subjects with asthma, current smoking, obesity,
      gender distribution and the combination of allergic diseases between the two
      studies had no differences. The most prominent causes of asthma exacerbation were
      cold air, respiratory infection and dust inhalation. Pulmonary function for 428
      asthma patients in Putuo survey was analyzed: 228 (53.3%) patients had FEV1%pred
      lower than 80%. Asthmatics older than 65 years had lower FEV1%pred than other age
      groups (p < 0.01). CONCLUSIONS: The prevalence of physician-diagnosed asthma in
      urban of Shanghai has increased in recent years. The most important causes of
      asthma exacerbations were cold air, respiratory infection and dust exposure. The
      proportion of individuals with decreased percent predicted forced expiratory
      volume of first second increased with age. Strengthening the prevention and
      treatment of asthma, especially in children with asthma, may decrease the health
      burden of asthma in the urban Chinese population.

PMID- 25387152
TI  - Non-monotonic relationships between emotional arousal and memory for color and
      location.
AB  - Recent research points to the decreased diagnostic value of subjective retrieval
      experience for memory accuracy for emotional stimuli. While for neutral stimuli
      rich recollective experiences are associated with better context memory than
      merely familiar memories this association appears questionable for emotional
      stimuli. The present research tested the implicit assumption that the effect of
      emotional arousal on memory is monotonic, that is, steadily increasing (or
      decreasing) with increasing arousal. In two experiments emotional arousal was
      manipulated in three steps using emotional pictures and subjective retrieval
      experience as well as context memory were assessed. The results show an inverted
      U-shape relationship between arousal and recognition memory but for context
      memory and retrieval experience the relationship was more complex. For frame
      colour, context memory decreased linearly while for spatial location it followed
      the inverted U-shape function. The complex, non-monotonic relationships between
      arousal and memory are discussed as possible explanations for earlier divergent
      findings. 

PMID- 25387153
TI  - Phosphatidylinositol 3-Kinase (PI3K) and phosphatidylinositol 3-kinase-related
      kinase (PIKK) inhibitors: importance of the morpholine ring.
AB  - Phosphatidylinositol 3-kinases (PI3Ks) and phosphatidylinositol 3-kinase-related
      protein kinases (PIKKs) are two related families of kinases that play key roles
      in regulation of cell proliferation, metabolism, migration, survival, and
      responses to diverse stresses including DNA damage. To design novel efficient
      strategies for treatment of cancer and other diseases, these kinases have been
      extensively studied. Despite their different nature, these two kinase families
      have related origin and share very similar kinase domains. Therefore, chemical
      inhibitors of these kinases usually carry analogous structural motifs. The most
      common feature of these inhibitors is a critical hydrogen bond to morpholine
      oxygen, initially present in the early nonspecific PI3K and PIKK inhibitor 3
      (LY294002), which served as a valuable chemical tool for development of many
      additional PI3K and PIKK inhibitors. While several PI3K pathway inhibitors have
      recently shown promising clinical responses, inhibitors of the DNA damage-related
      PIKKs remain thus far largely in preclinical development. 

PMID- 25387154
TI  - Catalytic oxygenation of sp3 "C-H" bonds with Ir(III) complexes of chelating
      triazoles and mesoionic carbenes.
AB  - Cp*-Ir(III) complexes with additional chelating ligands are known active pre
      catalysts for the oxygenation of C-H bonds. We present here eight examples of
      such complexes where the denticity of the chelating ligands has been varied from
      the well-known 2,2'-bpy through pyridyl-triazole, bi-triazole to ligands
      containing pyridyl-triazolylidene, triazolyl-triazolylidene and bi
      triazolylidenes. Additionally, we also compare the catalytic results to complexes
      containing chelating cyclometallated ligands with additional triazole or
      triazolylidene donors. Single crystal X-ray structural data are presented for all
      the new complexes that contain one or more triazolylidene donors of the mesoionic
      carbene type. We present the first example of a metal complex containing a
      chelating triazole-triazolylidene ligand. The results of the catalytic screening
      show that complexes containing unsymmetrical donors of the pyridyl-triazole or
      pyridyl-triazolylidene types are the most potent pre-catalysts for the C-H
      oxygenation of cyclooctane in the presence of either m-CPBA or NaIO4 as a
      sacrificial oxidant. These pre-catalysts can also be used to oxygenate C-H bonds
      in other substrates such as fluorene and ethyl benzene. The most potent pre
      catalysts presented here work with a lower catalyst loading and under milder
      conditions while delivering better product yields in comparison with related
      literature known Ir(III) pre-catalysts. These results thus point to the potential
      of ligands with unsymmetrical donors obtained through the click reaction in
      oxidation catalysis.

PMID- 25387155
TI  - Reconstruction of elbow flexion in arthrogryposis multiplex congenita type I:
      results of transfer of pectoralis major muscle with follow-up at skeletal
      maturity.
AB  - BACKGROUND: The purpose of this study was to analyze the results of a pectoralis
      major transfer to restore active elbow flexion in patients with extension elbow
      contracture in arthrogryposis. The hypotheses were: (1) this transfer ensures
      permanent useful elbow flexion; and (2) flexion elbow deformity will not progress
      during growth and after its cessation. METHODS: Unipolar transfer of the 3 distal
      parts of the pectoralis major muscle was used in 9 extremities of 5 patients (age
      range, 5 to 9 y; average age, 6.3 y) and the results were prospectively followed
      in the period of 13 to 16 years. Posterior elbow release was necessary in 5
      extremities to achieve passive flexion of 90 degrees before the transfer. The
      subjective evaluation of daily living activities and data on the physical
      examination of the range of movement of the elbow, muscle strength, and
      electrical activity of the transferred muscle were assessed. Two specimens from
      transferred muscles were histologically examined. RESULTS: All extremities
      achieved the active elbow flexion. Significant improvement of function for daily
      living activities was achieved in 5 extremities (55.5%). It includes the
      following results: 1 very good with flexion of 90 degrees and a deficit of
      extension of 35 degrees; 2 good with flexion of 92 and 100 degrees and a lack of
      extension of 42 and 45 degrees; and 2 satisfactory with a limited arc of motion
      between 20 and 45 degrees. Four extremities remained unsatisfactory with the arc
      of motion of 5 to 15 degrees. Significant elbow flexion contracture of 70 to 80
      degrees developed in 4 extremities. Extremities with a necessity of posterior
      elbow release achieved a limited range of movement or significant elbow flexion
      contracture. Electromyography corresponded to a partial denervation of the
      transferred muscle followed by reinervation. Histologic examinations showed
      partial atrophy with signs of ongoing regeneration. CONCLUSIONS: The hypotheses
      of the study were not confirmed, because this muscle transfer restores useful
      elbow flexion without flexion deformity if the passive flexion at children's age
      exceeds 90 degrees without a necessity of posterior release. In these cases,
      bilateral pectoralis to biceps transfer is recommended. LEVEL OF EVIDENCE: Level
      II.

PMID- 25387156
TI  - The relationship of the femoral physis and the medial patellofemoral ligament in
      children: a cadaveric study.
AB  - BACKGROUND: Patellar dislocations are common in skeletally immature athletes, and
      the medial patellofemoral ligament (MPFL) is an important primary restraint to
      lateral patellar translation. The relationship between the MPFL femoral origin
      footprint and femoral physis is unclear. The purpose of this study was to
      evaluate the MPFL femoral origin footprint and its relationship to the femoral
      physis in skeletally immature anatomic specimens. METHODS: Six skeletally
      immature cadaver knee specimens were examined through gross dissection (group A:
      1, 11, and 11 mo; and group B: 8, 10, and 11 y). Metallic markers were placed at
      the center of the MPFL femoral origin footprint. Computed tomography scans for
      each specimen were analyzed. The MPFL footprint width, and the vertical distances
      from the center and proximal extent of the MPFL footprint to the medial aspect of
      the physis were measured. RESULTS: The mean width of the MPFL femoral origin
      footprint was 0.70 cm (0.48 to 1.09 cm) and 1.12 cm (1.03 to 1.29 cm) for groups
      A and B, respectively. The mean distance from the center of the MPFL origin
      footprint to medial aspect of the distal femoral physis was 0.90 cm (0.52 to 1.30
      cm) and 0.40 cm (0.00 to 0.86 cm) distal to the physis for groups A and B,
      respectively. The mean distance from the proximal extent of the MPFL origin
      footprint to the medial aspect of the femoral physis was -0.55 cm (-0.28 to -1.03
      cm) and 0.16 cm (-0.34 to 0.64 cm) for groups A and B, respectively. CONCLUSIONS:
      All subjects were found to have a center of the MPFL origin footprint at or below
      the physis. The proximal extent of the MPFL origin footprint was found to extend
      above the physis in the 2 older specimens. CLINICAL RELEVANCE: The relationship
      of the MPFL origin footprint to the femoral physis in the skeletally immature is
      not well understood. These dissections may be useful to surgeons performing MPFL
      reconstructions in skeletally immature patients.

PMID- 25387157
TI  - Outcomes of children younger than 24 months with langerhans cell histiocytosis
      and bone involvement: a report from a single institution.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder that ranges
      from single-system to disseminated multisystem disease. Patients younger than 24
      months of age more commonly present with risk organ (liver, spleen, hematopoietic
      system, or lung) involvement at diagnosis and have a poor prognosis. Treatment
      approaches have changed over the last 25 years. Our goal was to describe the
      course and outcomes of patients younger than 24 months of age at diagnosis and
      identify the role of bone involvement in outcomes. METHODS: We conducted a
      retrospective chart review of patients diagnosed with LCH at Children's Hospital
      Los Angeles from 1984 to 2010, focusing on 71 patients younger than 24 months of
      age at diagnosis. RESULTS: Ten patients had single bone lesions at diagnosis and
      did well irrespective of therapy. The majority of patients (40/71 or 56%) had
      multiple bone lesions. Of the 37 patients with multisystem disease, 27 children
      (73%) had risk organ involvement. Fourteen patients with risk organ involvement
      received <= 6 months of initial chemotherapy with prednisone and vinblastine. Six
      of these patients had reactivation of the disease, and bone was the most frequent
      site of reactivation. Seven patients with risk organ involvement were treated
      with at least 12 months of chemotherapy. Only one of these patients had
      reactivation of the disease, and none died. The majority (7/10) of patients with
      risk organ involvement who progressed on therapy died despite multiple treatment
      regimens. CONCLUSIONS: Patients younger than 24 months of age at diagnosis are
      more likely to have multiple bone lesions than older patients, supporting that a
      radiographic skeletal survey at the time of LCH diagnosis is important to
      evaluate the extent of bone involvement. Bones were the most common site for
      reactivation for all patients. As expected, subjects with risk organ involvement
      had better outcomes when treated with systemic chemotherapy for at least 1 year.
      LEVEL OF EVIDENCE: As a retrospective review of all cases at our institution over
      a 26-year period, this article represents level IV evidence.

PMID- 25387158
TI  - A combined toxicity study of zinc oxide nanoparticles and vitamin C in food
      additives.
AB  - At present, safety evaluation standards for nanofood additives are made based on
      the toxic effects of a single additive. Since the size, surface properties and
      chemical nature influence the toxicity of nanomaterials, the toxicity may have
      dramatically changed when nanomaterials are used as food additives in a complex
      system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles
      (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased
      the cytotoxicity significantly compared with that of the ZnO only NPs. When the
      cells were exposed to ZnO NPs at a concentration less than 15 mg L(-1), or to Vc
      at a concentration less than 300 mg L(-1), there was no significant cytotoxicity,
      both in the case of gastric epithelial cell line (GES-1) and neural stem cells
      (NSCs). However, when 15 mg L(-1) of ZnO NPs and 300 mg L(-1) of Vc were
      introduced to cells together, the cell viability decreased sharply indicating
      significant cytotoxicity. Moreover, the significant increase in toxicity was also
      shown in the in vivo experiments. The dose of the ZnO NPs and Vc used in the in
      vivo study was calculated according to the state of food and nutrition enhancer
      standard. After repeated oral exposure to ZnO NPs plus Vc, the injury of the
      liver and kidneys in mice has been indicated by the change of these indices.
      These findings demonstrate that the synergistic toxicity presented in a complex
      system is essential for the toxicological evaluation and safety assessment of
      nanofood. 

PMID- 25387159
TI  - Novel multivariate methods for integration of genomics and proteomics data:
      applications in a kidney transplant rejection study.
AB  - Multi-omics research is a key ingredient of data-intensive life sciences
      research, permitting measurement of biological molecules at different functional
      levels in the same individual. For a complete picture at the biological systems
      level, appropriate statistical techniques must however be developed to integrate
      different 'omics' data sets (e.g., genomics and proteomics). We report here
      multivariate projection-based analyses approaches to genomics and proteomics data
      sets, using the case study of and applications to observations in kidney
      transplant patients who experienced an acute rejection event (n=20) versus non
      rejecting controls (n=20). In this data sets, we show how these novel
      methodologies might serve as promising tools for dimension reduction and
      selection of relevant features for different analytical frameworks. Unsupervised
      analyses highlighted the importance of post transplant time-of-rejection, while
      supervised analyses identified gene and protein signatures that together
      predicted rejection status with little time effect. The selected genes are part
      of biological pathways that are representative of immune responses. Gene
      enrichment profiles revealed increases in innate immune responses and neutrophil
      activities and a depletion of T lymphocyte related processes in rejection samples
      as compared to controls. In all, this article offers candidate biomarkers for
      future detection and monitoring of acute kidney transplant rejection, as well as
      ways forward for methodological advances to better harness multi-omics data sets.

PMID- 25387160
TI  - How Sedentary are Older People? A Systematic Review of the Amount of Sedentary
      Behavior.
AB  - BACKGROUND/OBJECTIVES: Sedentary behavior (SB), defined as sitting
      (nonexercising), reclining, and lying down (posture), or by low energy
      expenditure, is a public health risk independent to physical activity. The
      objective of this systematic literature review was to synthesize the available
      evidence on amount of SB reported by and measured in older adults. DATA SOURCE:
      Studies published between 1981 and 2014 were identified from electronic databases
      and manual searching. Large-scale population studies/surveys reporting the amount
      of SB (objective/ subjective) in older adults aged >= 60 years of age were
      included. Appraisal and synthesis was completed using MOOSE guidelines. RESULTS:
      349,698 adults aged >= 60 within 22 studies (10 countries and 1 EU-wide) were
      included. Objective measurement of SB shows that older adults spend an average of
      9.4 hr a day sedentary, equating to 65-80% of their waking day. Self-report of SB
      is lower, with average weighted self-reports being 5.3 hr daily. Within specific
      domains of SB, older adults report 3.3 hr in leisure sitting time and 3.3 hr
      watching TV. There is an association with more time spent in SB as age advances
      and a trend for older men to spend more time in SB than women. Conclusion/
      implications: Time spent sedentary ranges from 5.3-9.4 hr per waking day in older
      adults. With recent studies suggesting a link between SB, health, and well-being,
      independent of physical activity, this is an area important for successful aging.
      LIMITATIONS: Different methodologies of measurement and different reporting
      methods of SB made synthesis difficult. Estimated SB time from self-report is
      half of that measured objectively; suggesting that most self-report surveys of SB
      will vastly underestimate the actual time spent in SB.

PMID- 25387161
TI  - Existence and stability of pseudo almost periodic solutions for shunting
      inhibitory cellular neural networks with neutral type delays and time-varying
      leakage delays.
AB  - In this paper, shunting inhibitory cellular neural networks(SICNNs) with neutral
      type delays and time-varying leakage delays are investigated. By applying
      Lyapunov functional method and differential inequality techniques, a set of
      sufficient conditions are obtained for the existence and exponential stability of
      pseudo almost periodic solutions of the model. An example is given to support the
      theoretical findings. Our results improve and generalize those of the previous
      studies. 

PMID- 25387163
TI  - Function and Regulation of Ferredoxins in the Cyanobacterium, Synechocystis
      PCC6803: Recent Advances.
AB  - Ferredoxins (Fed), occurring in most organisms, are small proteins that use their
      iron-sulfur cluster to distribute electrons to various metabolic pathways, likely
      including hydrogen production. Here, we summarize the current knowledge on
      ferredoxins in cyanobacteria, the prokaryotes regarded as important producers of
      the oxygenic atmosphere and biomass for the food chain, as well as promising cell
      factories for biofuel production. Most studies of ferredoxins were performed in
      the model strain, Synechocystis PCC6803, which possesses nine highly-conserved
      ferredoxins encoded by monocistronic or operonic genes, some of which are
      localized in conserved genome regions. Fed1, encoded by a light-inducible gene,
      is a highly abundant protein essential to photosynthesis. Fed2-Fed9, encoded by
      genes differently regulated by trophic conditions, are low-abundant proteins that
      play prominent roles in the tolerance to environmental stresses. Concerning the
      selectivity/redundancy of ferredoxin, we report that Fed1, Fed7 and Fed9 belong
      to ferredoxin-glutaredoxin-thioredoxin crosstalk pathways operating in the
      protection against oxidative and metal stresses. Furthermore, Fed7 specifically
      interacts with a DnaJ-like protein, an interaction that has been conserved in
      photosynthetic eukaryotes in the form of a composite protein comprising DnaJ- and
      Fed7-like domains. Fed9 specifically interacts with the Flv3 flavodiiron protein
      acting in the photoreduction of O2 to H2O. 

PMID- 25387164
TI  - Linear and non-linear wall friction of wet foams.
AB  - We study the wall slip of aqueous foams with a high liquid content. We use a set
      up where, driven by buoyancy, a foam creeps along an inclined smooth solid wall
      which is immersed in the foaming solution. This configuration allows the force
      driving the bubble motion and the bubble confinement in the vicinity of the wall
      to be tuned independently. First, we consider bubble monolayers with small Bond
      number Bo < 1 and measure the relation between the friction force F and the
      bubble velocity V. For bubbles which are so small that they are almost spherical,
      the friction law F ? V is Stokes-like. The analysis shows that the minimal
      thickness of the lubricating contact between the bubble and the wall is governed
      by DLVO long-range forces. Our results are the first evidence of this predicted
      linear friction regime for creeping bubbles. Due to buoyancy, large bubbles
      flatten against the wall. In this case, dissipation arises because of viscous
      flow in the dynamic meniscus between the contact film and the spherical part of
      the bubble. It leads to a non-linear Bretherton-like friction law F ? V(2/3), as
      expected for slipping bubbles with mobile liquid-gas interfaces. The Stokes-like
      friction dominates for capillary numbers Ca larger than the crossover value Ca* ~
      Bo(3/2). The overall friction force can be expressed as the sum of these two
      contributions. On this basis, we then study 3D foams close to the jamming
      transition with osmotic pressures Pi small compared to the capillary pressure Pc.
      We measure the wall shear stress tau as a function of the capillary number, and
      we evidence two friction regimes that are consistent with those found for the
      monolayer. Similarly to this latter case, the total shear stress can be expressed
      as the sum of the Stokes-like friction term tau ? Ca and the Bretherton-like one
      tau ? Ca(2/3). However, for a 3D foam, the crossover at a capillary number Ca**
      between both regimes is governed by the ratio of the osmotic pressure to the
      capillary pressure, such that Ca** ~ (Pi/Pc)(3/2). 

PMID- 25387165
TI  - Characteristics of NRS-2002 Nutritional Risk Screening in patients hospitalized
      for secondary cardiovascular prevention and rehabilitation.
AB  - OBJECTIVE: The aim of our study was to assess the prevalence and characteristics
      of nutritional risk in patients scheduled for cardiovascular rehabilitation.
      BACKGROUND: Knowledge concerning nutritional aspects of cardiovascular diseases
      is contemporary limited. METHODS: Nutritional risk screening using a standardized
      Nutritional Risk Screening-2002 (NRS-2002) questionnaire was performed on a
      cohort of consecutive patients scheduled for rehabilitation 1-6 months after
      treatment for ischemic, valvular, or combined causes of heart diseases. Baseline
      weight was available for more than 80% of patients. RESULTS: The study population
      consisted of 317 patients, aged 23-85 years, with a mean age of 62.5 +/- 11.3
      years. Male to female share was 253 (79.8%) and 64 (20.2%), respectively. Twenty
      eight (8.8%) were treated for myocardial infarction conservatively, 151 (47.6%)
      by percutaneous coronary interventions, and 145 (45.7%) by surgery. NRS-2002 was
      3.56 +/- 1.54 in range 0-6. A high correlation was found between the NRS-2002 and
      percentage weight loss history (rho = 0.813; p <0.001). Significant differences
      according to increased nutritional risk (NRS-2002 >= 3) were found within age
      groups (p < 0.001), disease etiology (p = 0.002), cardiovascular treatments (p <
      0.001), and grades of renal function (p < 0.001). Odds for developing increased
      nutritional risk (NRS-2002 >= 3) were significant for cardiovascular treatments
      (odds ratio [OR] = 4.35, 95% confidence interval [CI], 2.28-8.30, p < 0.001), age
      (OR = 3.19, 95% CI, 2.00-5.09, p < 0.001), grade of renal function (OR = 1.91,
      95% CI, 1.17-3.09, p = 0.009), diabetes mellitus (OR = 2.37, 95% CI, 1.09-5.16, p
      = 0.029), and any psychological disturbance (OR = 2.04, 95% CI, 1.06-3.90, p =
      0.032). CONCLUSIONS: Pronounced nutritional risk frequently existed among
      patients at stationary cardiovascular rehabilitation. Nutritional risk was
      connected with preceding cardiovascular treatments, patient age, and renal
      function. Further studies concerning nutritional risk and its connections with
      clinical outcomes might serve as a resourceful perspective to improve outcomes or
      quality of care for the entities from the cardiovascular diseases continuum.

PMID- 25387166
TI  - Electrochemical synthesis of copper nanoparticles using cuprous oxide as a
      precursor in choline chloride-urea deep eutectic solvent: nucleation and growth
      mechanism.
AB  - The electrochemical nucleation and growth kinetics of copper nanoparticles on a
      Ni electrode have been studied with cyclic voltammetry and chronoamperometry in
      the choline chloride (ChCl)-urea based deep eutectic solvent (DES). The copper
      source was introduced into the solvent by the dissolution of Cu(I) oxide (Cu2O).
      Cyclic voltammetry indicates that the electroreduction of Cu(I) species in the
      DES is a diffusion-controlled quasi-reversible process. The analysis of the
      chronoamperometric transient behavior during electrodeposition suggests that the
      deposition of copper on the Ni electrode at low temperatures follows a
      progressive nucleation and three-dimensional growth controlled by diffusion. The
      effect of temperature on the diffusion coefficient of Cu(I) species that is
      present in the solvent and electron transfer rate constant obeys the Arrhenius
      law, according to which the activation energies are estimated to be 49.20 and
      21.72 kJ mol(-1), respectively. The initial stage of morphological study
      demonstrates that both electrode potential and temperature play important roles
      in controlling the nucleation and growth kinetics of the nanocrystals during the
      electrodeposition process. Electrode potential is observed to affect mainly the
      nucleation process, whereas temperature makes a major contribution to the growth
      process.

PMID- 25387162
TI  - Microgravity-induced fluid shift and ophthalmic changes.
AB  - Although changes to visual acuity in spaceflight have been observed in some
      astronauts since the early days of the space program, the impact to the crew was
      considered minor. Since that time, missions to the International Space Station
      have extended the typical duration of time spent in microgravity from a few days
      or weeks to many months. This has been accompanied by the emergence of a variety
      of ophthalmic pathologies in a significant proportion of long-duration
      crewmembers, including globe flattening, choroidal folding, optic disc edema, and
      optic nerve kinking, among others. The clinical findings of affected astronauts
      are reminiscent of terrestrial pathologies such as idiopathic intracranial
      hypertension that are characterized by high intracranial pressure. As a result,
      NASA has placed an emphasis on determining the relevant factors and their
      interactions that are responsible for detrimental ophthalmic response to space.
      This article will describe the Visual Impairment and Intracranial Pressure
      syndrome, link it to key factors in physiological adaptation to the microgravity
      environment, particularly a cephalad shifting of bodily fluids, and discuss the
      implications for ocular biomechanics and physiological function in long-duration
      spaceflight. 

PMID- 25387167
TI  - Safety and Efficacy of Autologous Intra-articular Platelet Lysates in Early and
      Intermediate Knee Osteoarthrosis in Humans: A Prospective Open-Label Study.
AB  - OBJECTIVE: To explore the safety and benefit from intra-articular autologous
      platelet lysate (PL) injection in early and intermediate knee osteoarthritis.
      DESIGN: Open-label prospective study. SETTING: Laboratory. PATIENTS: Adult
      patients, aged 35 to 70 years, with a history of chronic pain or swelling on one
      or both knees and imaging findings (radiograph or magnetic resonance imaging) of
      degenerative changes in the joint of grade I or II on the Kellgren scale were
      included. INTERVENTIONS: Autologous PL was given in the knee joint by
      percutaneous intra-articular route every 3 weeks for a total of 3 injections.
      MAIN OUTCOME MEASURES: Response was evaluated by nonnormalized Knee
      Osteoarthritis and Disability Outcome Score (KOOS). RESULTS: There was a
      significant improvement in the 5 aspects evaluated at weeks 32 and 52 compared
      with baseline. Symptoms score significantly improved at weeks 32 and 52 from a
      mean of 11.1 at baseline to 9.0 (P < 0.0001) and 8.7 (P < 0.0001). Stiffness
      score significantly improved at weeks 32 and 52 from 2.2 at baseline to 1.7 (P <
      0.022) and 1.6 (P < 0.016). Pain score improved at 32 weeks and at 52 weeks from
      a baseline of 14.2 to 9.8 (P < 0.0001) and 9.2 (P < 0.0001). Daily Living score
      improved from 25.0 to 18.7 at 32 weeks (P < 0.0001) and to 15.6 at 52 weeks (P <
      0.0001). Sport score improved from 10.7 to 8.4 at 32 weeks (P < 0.0001) and to
      8.1 at 52 weeks (P < 0.0001). CONCLUSIONS: Intra-articular PL significantly
      improved score of all aspects evaluated by KOOS. Platelet lysate seems to be a
      safe product. CLINICAL RELEVANCE: To the best of our knowledge, this is the first
      clinical study addressing the use of autologous PL as a treatment measure for
      knee osteoarthrosis (KOA). There are no studies published regarding the treatment
      of KOA by intra-articular injections of PL. The previous studies were on the use
      of platelet-rich plasma (PRP) treatment for KOA. Platelet-rich plasma use has
      been in place for several years, however, a standardized protocol has not yet
      been established. Platelet lysate represents a safe, economical, easy to prepare,
      and easy to apply source of growth factors in the treatment of KOA. A head-to
      head study is needed to compare PRP with PL in KOA.

PMID- 25387168
TI  - Characteristics of Pediatric and Adolescent Concussion Clinic Patients With
      Postconcussion Amnesia.
AB  - OBJECTIVE: The current study examines the demographics, injury characteristics,
      and outcomes associated with the presence of postconcussion amnesia in young
      concussion clinic patients. DESIGN: Cross-sectional, retrospective clinical
      cohort. SETTING: Concussion services clinic. PATIENTS: Pediatric and adolescent
      concussion services program patients, presenting within 10 days postinjury, aged
      10-18 years, with the goal of returning to sport (n = 245). ASSESSMENT OF RISK
      FACTORS: Age, gender, race, head trauma history, injury mechanism, loss of
      consciousness (LOC), injury-related visit to an emergency department, cognitive
      and balance scores, symptoms, and management recommendations. MAIN OUTCOME
      MEASURES: Univariate and multivariate analyses determined adjusted odds ratios
      for reported presence of any postconcussion amnesia (anterograde or retrograde).
      RESULTS: Factors associated with amnesia (univariate, P < 0.10) and included in
      the multivariate model were race, head trauma history, mechanism of injury, LOC,
      injury-related visit to an emergency department, management recommendations and
      time of injury and initial visit symptom severity. Age and gender were also
      included in the model due to biological significance. Of the 245 patients, 181
      had data for all model variables. Of the 181 patients, 58 reported amnesia.
      History of head trauma [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.3
      5.7]; time of injury (TOI) symptom severity >75th percentile (OR, 2.6; 95% CI,
      1.2-5.3) and LOC (OR, 2.2; 95% CI, 1.1-4.6) were found to have significant and
      independent relationships with amnesia in the multivariate model. CONCLUSIONS:
      This study illustrates that patients presenting with postconcussion amnesia are
      more likely to have a history of head trauma, LOC, and greater symptom severity.
      Future research is needed to better understand amnesia following concussion.
      CLINICAL RELEVANCE: Amnesia presence, previous head trauma, LOC, and increased
      symptom severity may aid in identifying patients with a greater initial injury
      burden who warrant closer observation and more conservative management.

PMID- 25387171
TI  - Liberty Loan Parade: Arthur Clifton Goodwin.

PMID- 25387172
TI  - IOM report calls for transformation of end-of-life care.

PMID- 25387181
TI  - Should life insurers have access to genetic test results?

PMID- 25387182
TI  - Overcoming the reimbursement barriers for clinical sequencing.

PMID- 25387183
TI  - Selecting a specialist: adding evidence to the clinical practice of making
      referrals.

PMID- 25387184
TI  - A piece of my mind. The quality of mercy: will you be my doctor?

PMID- 25387185
TI  - Quality and costs of end-of-life care: the need for transparency and
      accountability.

PMID- 25387186
TI  - Association between the Medicare hospice benefit and health care utilization and
      costs for patients with poor-prognosis cancer.
AB  - IMPORTANCE: More patients with cancer use hospice currently than ever before, but
      there are indications that care intensity outside of hospice is increasing, and
      length of hospice stay decreasing. Uncertainties regarding how hospice affects
      health care utilization and costs have hampered efforts to promote it. OBJECTIVE:
      To compare utilization and costs of health care for patients with poor-prognosis
      cancers enrolled in hospice vs similar patients without hospice care. DESIGN,
      SETTING, AND PARTICIPANTS: Matched cohort study of patients in hospice and
      nonhospice care using a nationally representative 20% sample of Medicare fee-for
      service beneficiaries who died in 2011. Patients with poor-prognosis cancers (eg,
      brain, pancreatic, metastatic malignancies) enrolled in hospice before death were
      matched to similar patients who died without hospice care. EXPOSURES: Period
      between hospice enrollment and death for hospice beneficiaries, and the
      equivalent period of nonhospice care before death for matched nonhospice
      patients. MAIN OUTCOMES AND MEASURES: Health care utilization including
      hospitalizations and procedures, place of death, cost trajectories before and
      after hospice start, and cumulative costs, all during the last year of life.
      RESULTS: Among 86,851 patients with poor-prognosis cancers, median time from
      first poor-prognosis diagnosis to death was 13 months (interquartile range [IQR],
      3-34), and 51,924 patients (60%) entered hospice before death. Matching yielded a
      cohort balanced on age, sex, region, time from poor-prognosis diagnosis to death,
      and baseline care utilization, with 18,165 patients in the hospice group and
      18,165 in the nonhospice group. After matching, 11% of nonhospice and 1% of
      hospice beneficiaries who had cancer-directed therapy after exposure were
      excluded. Median hospice duration was 11 days. After exposure, nonhospice
      beneficiaries had significantly more hospitalizations (65% [95% CI, 64%-66%], vs
      hospice with 42% [95% CI, 42%-43%]; risk ratio, 1.5 [95% CI, 1.5-1.6]), intensive
      care (36% [95% CI, 35%-37%], vs hospice with 15% [95% CI, 14%-15%]; risk ratio,
      2.4 [95% CI, 2.3-2.5]), and invasive procedures (51% [95% CI, 50%-52%], vs
      hospice with 27% [95% CI, 26%-27%]; risk ratio, 1.9 [95% CI, 1.9-2.0]), largely
      for acute conditions not directly related to cancer; and 74% (95% CI, 74%-75%) of
      nonhospice beneficiaries died in hospitals and nursing facilities compared with
      14% (95% CI, 14%-15%) of hospice beneficiaries. Costs for hospice and nonhospice
      beneficiaries were not significantly different at baseline, but diverged after
      hospice start. Total costs over the last year of life were $71,517 (95% CI,
      $70,543-72,490) for nonhospice and $62,819 (95% CI, $62,082-63,557) for hospice,
      a statistically significant difference of $8697 (95% CI, $7560-$9835).
      CONCLUSIONS AND RELEVANCE: In this sample of Medicare fee-for-service
      beneficiaries with poor-prognosis cancer, those receiving hospice care vs not
      (control), had significantly lower rates of hospitalization, intensive care unit
      admission, and invasive procedures at the end of life, along with significantly
      lower total costs during the last year of life.

PMID- 25387187
TI  - Evaluation of the association of maternal pertussis vaccination with obstetric
      events and birth outcomes.
AB  - IMPORTANCE: In 2010, due to a pertussis outbreak and neonatal deaths, the
      California Department of Health recommended that the tetanus toxoid, reduced
      diphtheria toxoid, and acellular pertussis vaccine (Tdap) be administered during
      pregnancy. Tdap is now recommended by the Advisory Committee on Immunization
      Practices for all pregnant women, preferably between 27 and 36 weeks' gestation.
      Limited data exist on Tdap safety during pregnancy. OBJECTIVE: To evaluate
      whether maternal Tdap vaccination during pregnancy is associated with increased
      risks of adverse obstetric events or adverse birth outcomes. DESIGN AND SETTING:
      Retrospective, observational cohort study using administrative health care
      databases from 2 California Vaccine Safety Datalink sites. PARTICIPANTS AND
      EXPOSURES: Of 123,494 women with singleton pregnancies ending in a live birth
      between January 1, 2010, and November 15, 2012, 26,229 (21%) received Tdap during
      pregnancy and 97,265 did not. MAIN OUTCOMES AND MEASURES: Risks of small-for
      gestational-age (SGA) births (<10th percentile), chorioamnionitis, preterm birth
      (<37 weeks' gestation), and hypertensive disorders of pregnancy were evaluated.
      Relative risk (RR) estimates were adjusted for site, receipt of another vaccine
      during pregnancy, and propensity to receive Tdap during pregnancy. Cox regression
      was used for preterm delivery, and Poisson regression for other outcomes.
      RESULTS: Vaccination was not associated with increased risks of adverse birth
      outcomes: crude estimates for preterm delivery were 6.3% of vaccinated and 7.8%
      of unvaccinated women (adjusted RR, 1.03; 95% CI, 0.97-1.09); 8.4% of vaccinated
      and 8.3% of unvaccinated had an SGA birth (adjusted RR, 1.00; 95% CI, 0.96-1.06).
      Receipt of Tdap before 20 weeks was not associated with hypertensive disorder of
      pregnancy (adjusted RR, 1.09; 95% CI, 0.99-1.20); chorioamnionitis was diagnosed
      in 6.1% of vaccinated and 5.5% of unvaccinated women (adjusted RR, 1.19; 95% CI,
      1.13-1.26). CONCLUSIONS AND RELEVANCE: In this cohort of women with singleton
      pregnancies that ended in live birth, receipt of Tdap during pregnancy was not
      associated with increased risk of hypertensive disorders of pregnancy or preterm
      or SGA birth, although a small but statistically significant increased risk of
      chorioamnionitis diagnosis was observed.

PMID- 25387188
TI  - Treatment of syphilis: a systematic review.
AB  - IMPORTANCE: The incidence of syphilis in the United States is increasing; it is
      estimated that more than 55,000 new infections will occur in 2014. Treatment
      regimens are controversial, especially in specific populations, and assessing
      treatment response based on serology remains a challenge. OBJECTIVE: To review
      evidence regarding penicillin and nonpenicillin regimens, implications of the
      "serofast state," and treatment of specific populations including those with
      neurosyphilis or human immunodeficiency virus (HIV) infection and pregnant women.
      EVIDENCE REVIEW: We searched MEDLINE for English-language human treatment studies
      dating from January 1965 until July 2014. The American Heart Association
      classification system was used to rate quality of evidence. FINDINGS: We included
      102 articles in our review, consisting of randomized trials, meta-analyses, and
      cohort studies. Case reports and small series were excluded unless they were the
      only studies providing evidence for a specific treatment strategy. We included 11
      randomized trials. Evidence regarding penicillin and nonpenicillin regimens was
      reviewed from studies involving 11,102 patients. Data on the treatment of early
      syphilis support the use of a single intramuscular injection of 2.4 million U of
      benzathine penicillin G, with studies reporting 90% to 100% treatment success
      rates. The value of multiple-dose treatment of early syphilis is uncertain,
      especially in HIV-infected individuals. Less evidence is available regarding
      therapy for late and late latent syphilis. Following treatment, nontreponemal
      serologic titers should decline in a stable pattern, but a significant proportion
      of patients may remain seropositive (the "serofast state"). Serologic response to
      treatment should be evident by 6 months in early syphilis but is generally slower
      (12-24 months) for latent syphilis. Evidence defining treatment for HIV-infected
      persons and for pregnant women is limited, but available data support penicillin
      as first-line therapy. CONCLUSIONS AND RELEVANCE: The mainstay of syphilis
      treatment is parenteral penicillin G despite the relatively modest clinical trial
      data that support its use.

PMID- 25387189
TI  - Food marketing to youth: serious business.

PMID- 25387190
TI  - Use of HPV vaccine in males and females.

PMID- 25387191
TI  - RPR and the serologic diagnosis of syphilis.

PMID- 25387192
TI  - Life expectancy in patients with chronic HCV infection and cirrhosis compared
      with a general population.

PMID- 25387193
TI  - Erythropoietin for traumatic brain injury.

PMID- 25387194
TI  - Erythropoietin for traumatic brain injury--reply.

PMID- 25387195
TI  - Time since stroke and risk of adverse outcomes after surgery.

PMID- 25387196
TI  - Time since stroke and risk of adverse outcomes after surgery--reply.

PMID- 25387197
TI  - Medicalization of marijuana.

PMID- 25387198
TI  - Medicalization of marijuana--reply.

PMID- 25387204
TI  - The etiology of syphilis.

PMID- 25387205
TI  - Editorial comment for Choi et al.

PMID- 25387206
TI  - Evolution of species interactions determines microbial community productivity in
      new environments.
AB  - Diversity generally increases ecosystem productivity over short timescales. Over
      longer timescales, both ecological and evolutionary responses to new environments
      could alter productivity and diversity-productivity relationships. In turn,
      diversity might affect how component species adapt to new conditions. We tested
      these ideas by culturing artificial microbial communities containing between 1
      and 12 species in three different environments for ~60 generations. The
      relationship between community yields and diversity became steeper over time in
      one environment. This occurred despite a general tendency for the separate yields
      of isolates of constituent species to be lower at the end if they had evolved in
      a more diverse community. Statistical comparisons of community and species yields
      showed that species interactions had evolved to be less negative over time,
      especially in more diverse communities. Diversity and evolution therefore
      interacted to enhance community productivity in a new environment. 

PMID- 25387207
TI  - Hair as a biomarker of systemic exposure to polybrominated diphenyl ethers.
AB  - The efficacy of using hair as a biomarker for exposure to polybrominated diphenyl
      ether (PBDE) flame retardants was assessed in humans and an animal model. Paired
      human hair and serum samples were obtained from adult men and women (n = 50). In
      parallel, hair, serum, liver, and fat were collected from adult male Sprague
      Dawley rats exposed to increasing doses of the PBDE mixture found in house dust
      for 70 days via the diet. All samples were analyzed by GC-MS for eight common
      PBDEs: BDE-28, -47, -99, -100, -153, -154, -183, and -209. Paired human hair and
      serum samples had five congeners (BDE-28, -47, -99, -100, and -154) with
      significant individual correlations (0.345-0.566). In rat samples, BDE-28 and BDE
      183 were frequently below the level of detection. Significant correlations were
      observed for BDE-47, -99, -100, -153, -154, and -209 in rat hair, serum, liver,
      and fat across doses, with r values ranging from 0.803 to 0.988; weaker
      correlations were observed between hair and other tissues when data from the
      lowest dose group or for BDE-209 were analyzed. Thus, human and rat hair PBDE
      measurements correlate strongly with those in alternative matrices, validating
      the use of hair as a noninvasive biomarker of long-term PBDE exposure. 

PMID- 25387208
TI  - Feasibility of the interferon-gamma enzyme-linked immunospot assay in chronic
      renal failure patients and immunocompetent subjects: a head-to-head comparison.
AB  - Diagnosis of latent Mycobacterium tuberculosis infection (LTBI) by the tuberculin
      skin test (TST) is hampered due to anergy and impaired sensitivity in chronic
      renal failure (CRF) patients. We aimed to compare the diagnostic performance of
      the TST with that of interferon-gamma immunospot (T-SPOT.TB(r)) assay in
      diagnosing LTBI in CRF and immunocompetent (IC) patients. A total of 74 CRF and
      75 IC patients prospectively underwent the TST and T-SPOT.TB. Latent M.
      tuberculosis infection estimated by TST and T-SPOT.TB was detected in 69% and 43
      of CRF; 52 and 35% of IC patients, respectively. The sensitivity and specificity
      of the T-SPOT.TB were 73 and 74% in IC, whereas 50 and 55% in CRF patients. In
      conclusion, the prevalence of LTBI was noteworthy in both IC and CRF patients. T
      SPOT.TB was less sensitive and specific than the IC group in CRF patients. Both T
      SPOT.TB and TST were not associated with the TB exposure.

PMID- 25387209
TI  - Overview of prescription omega-3 fatty acid products for hypertriglyceridemia.
AB  - Patients with elevated triglycerides (TG) may be at a higher risk for
      cardiovascular (CV) disease. Omega-3 fatty acids (OM3FAs), particularly the long
      chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      effectively reduce TG and thus may impact CV outcomes; however, clinical data
      have been inconsistent. This review discusses the efficacy, safety, and key
      considerations of currently approved prescription OM3FA products in patients with
      elevated TG with or without concomitant elevations in other atherogenic
      parameters. Currently, 6 prescription OM3FA formulations are approved in the
      United States: omega-3-acid ethyl esters (Lovaza, Omtryg, and 2 generic
      formulations), omega-3-carboxylic acids (Epanova), which contain both EPA and
      DHA, and icosapent ethyl (Vascepa), which is an EPA-only formulation. All
      prescription OM3FA products effectively lower TG, with the magnitude of TG
      reduction affected by baseline TG level. Products that contain DHA can raise
      levels of low-density lipoprotein cholesterol, which is of particular concern in
      patients with atherosclerosis; Vascepa, however, does not raise these levels and
      therefore provides these patients with another option. Long-term outcomes trials
      for Vascepa (ongoing) and Epanova (planned) will help clarify the potential CV
      benefits in patients with persistent hypertriglyceridemia despite statin therapy.

PMID- 25387210
TI  - Reversal agents in development for the new oral anticoagulants.
AB  - The new oral anticoagulants have many advantages over vitamin K antagonists, but
      they are still associated with a troublesome incidence of major bleeding.
      Additionally, the absence of a reversal agent for the new oral anticoagulants is
      a barrier to their more widespread use. Currently, there are 3 potential reversal
      agents in development: idarucizumab is a humanized murine monoclonal antibody
      fragment directed specifically at dabigatran; andexanet alfa is a recombinant
      modified decoy factor Xa that binds to factor Xa inhibitors; and PER977 is a
      small molecule that binds to factor Xa and IIa inhibitors and to heparin-based
      anticoagulants through charge interaction. These agents have undergone phase I
      clinical testing, appear to be well tolerated in healthy volunteers, and are
      effective in neutralizing their respective targets. All 3 are currently
      undergoing or entering into a phase II or III clinical study. This article
      reviews the available data for idarucizumab, andexanet alfa, and PER977. 

PMID- 25387211
TI  - Diagnosis, treatment, and prevention of venous thromboembolism in pregnancy.
AB  - Pregnancy and the puerperium put women at increased risk of venous
      thromboembolism (VTE) due to both baseline maternal risk factors and the
      development of pregnancy-related prothrombotic anatomic and physiologic changes.
      Pregnant women are at an approximately 5-fold increased risk of VTE compared with
      nonpregnant women, and the risk of VTE increases further (to >= 20-fold) in
      puerperium; risk remains increased until approximately 12 weeks postpartum.
      Pregnancy-related VTE accounts for about 10% of maternal deaths in the developed
      world. Clinicians should promptly evaluate any signs or symptoms suspicious for
      VTE, generally starting with ultrasound of the lower extremities. For treatment
      of women with established VTE, low molecular weight heparins (LMWHs) are
      preferred due to a favorable safety and efficacy profile. Unfractionated heparin
      (UFH) and potentially fondaparinux are alternatives. Warfarin should be avoided
      in the antepartum period due to teratogenicity, and the non-vitamin K oral
      anticoagulants are currently not recommended due to the lack of data. Low
      molecular weight heparin, UFH, and warfarin are all acceptable in the postpartum
      period and for breast-feeding women, but the non-vitamin K oral anticoagulants
      should be avoided. Prophylaxis (generally with LMWH or in some cases UFH) is
      recommended for women at highest risk of pregnancy-related VTE, such as those
      with inherited thrombophilias and a strong family or personal history of VTE.
      Prophylaxis with LMWH and aspirin is recommended for women with antiphospholipid
      syndrome. Clinicians should engage in multidisciplinary discussion, particularly
      around the time of delivery, to manage the details of anticoagulation in their
      pregnant patients. 

PMID- 25387212
TI  - The new cholesterol treatment guidelines from the American College of
      Cardiology/American Heart Association, 2013: what clinicians need to know.
AB  - The new American College of Cardiology/American Heart Association blood
      cholesterol guidelines of 2013 are the first major revision of cholesterol
      therapy guidance in over a decade. Commonly used low-density lipoprotein
      cholesterol (LDL-C) target goals have been abrogated in favor of intensity of
      statin therapy, more in line with data from randomized clinical trials. Four
      groups of adult patients have been identified from these studies who will most
      benefit from statins: patients with atherosclerotic cardiovascular disease
      (ASCVD); patients with primary elevations of LDL-C >= 190 mg/dL; diabetic
      patients between age 40 and 75 years without ASCVD whose LDL-C is between 70 and
      189 mg/dL; and patients between age 40 and 75 years without ASCVD or diabetes
      with LDL-C between 70 and 189 mg/dL and an estimated 10-year ASCVD risk of 7.5%
      or higher. This last primary prevention group has engendered the most controversy
      because the newly recommended risk calculator may overestimate risk or the 7.5%
      threshold may be too low, thereby subjecting too many patients to statins
      unnecessarily. This review summarizes the latest guidelines and pertinent
      evidence, and provides case examples to help clinicians familiarize themselves
      with the new recommendations. 

PMID- 25387213
TI  - Impact of statins in outcomes of septic patients: a systematic review.
AB  - BACKGROUND: The pleiotropic effects of statins have prompted considerable
      research in fields other than cardiovascular disease. We reviewed the literature
      aiming to summarize and critically evaluate the current evidence about the
      potential use of statins in sepsis. MATERIALS AND METHODS: We searched the
      Pubmed, SciELO, and Cochrane electronic databases from inception through November
      1, 2013, for randomized controlled trials (RCTs) and cohort studies that examined
      the association between statin use (upon hospital admission or previous users)
      and the risk or outcome of sepsis. Data on study characteristics, measurement of
      statin use, and outcomes (adjusted for potential confounders) were extracted. We
      structured our review according to the Principles of Reporting in Systematic
      Reviews and Meta-Analysis criteria. Quality assessment of cohort studies was
      performed using the Ottawa-Newcastle Scale. RESULTS: Twenty-three cohort studies
      and 5 RCTs were eligible, comprising 42 549 statin users and 54 201 non-statin
      users, from 1995 to 2013. The populations included varied from patients admitted
      to general wards or intensive care units with bacterial infections, community
      acquired pneumonia, ventilator-associated pneumonia, bacteremia, or sepsis, to
      outpatients with chronic kidney disease or established cardiovascular disease.
      Overall, 16 studies reported a benefit from statin use in morbidity or mortality
      outcomes (range of adjusted odds ratio, 0.06-0.62; alpha = 0.05). The remaining
      12 studies found no protective effect associated with statin use upon hospital
      admission or previous users. Among the 5 RCTs, none demonstrated a reduction in
      mortality. CONCLUSION: There is insufficient evidence to support the use of
      statins in patients with sepsis, as the existing studies failed to prove a
      consistent mortality benefit. More clinical trials are warranted to provide more
      conclusive knowledge and ultimately change clinical practice.

PMID- 25387214
TI  - Treatment of hypertension in patients with atherosclerotic renal artery stenosis,
      updated.
AB  - Atherosclerotic renal artery stenosis (ARAS) is a fairly common disease of
      elderly patients and is discovered incidentally in 6.3% to 38% in those
      undergoing diagnostic cardiac or abdominal angiography. Of those patients
      diagnosed with renal artery stenosis, in 90% it is due to ARAS and in 10% to
      fibromuscular dysplasia (FMD), which is a disease of younger persons, mostly
      females. Renal artery stenosis is frequently associated with hypertension and
      impaired renal function, and it is perceived by many physicians as the primary
      cause of hypertension and renal failure. For this reason, they believe that
      hypertension and renal failure can be significantly improved by performing
      percutaneous transluminal renal angioplasty (PTRA) with a stent placement as the
      preferred treatment instead of medical therapy. This practice has led to an
      increase in angioplasties, especially by interventional cardiologists who are
      familiar with the procedure. However, the results of several randomized studies
      comparing interventional therapy with medical therapy have shown no significant
      difference between the 2 treatment modalities in blood pressure reduction and
      prevention and in worsening of renal function. Similar results have been found by
      nonrandomized trials in patients treated selectively with PTRA. For this review,
      a Medline search was conducted of the English-language literature from January 1,
      2006 to December 31, 2013, using the terms atherosclerotic renal artery stenosis
      and renal artery stenosis; 6 pertinent randomized studies were selected. These
      studies, with collateral literature, are discussed in this review. The data show
      that PTRA with stent plus medical therapy in patients with ARAS is not superior
      to medical therapy alone in lowering the blood pressure, in preventing renal
      function deterioration, and in reducing all-cause mortality, cardiovascular
      morbidity or mortality, and strokes. 

PMID- 25387215
TI  - Descending thoracic aortic aneurysm: case presentation and review.
AB  - Descending thoracic aortic aneurysms, similar to other aneurysms, are often
      incidentally diagnosed in patients with unrelated complaints. Management of these
      aneurysms is largely dependent on their size and anatomy. Most individuals with
      asymptomatic descending thoracic aortic aneurysms may be safely managed with
      cardiovascular risk factor modification until the aneurysm size reaches 6 cm. A
      subset of individuals, such as those whose descending thoracic aortic aneurysm
      measures > 6 cm or in cases of rapid growth, should be offered repair,
      increasingly performed via an endovascular approach. The higher risk of aneurysm
      rupture in women poses a unique consideration, although to date no gender
      specific consensus screening guideline exists for aneurysmal disease of the
      thoracic aorta. 

PMID- 25387216
TI  - Virgin coconut oil and its potential cardioprotective effects.
AB  - Emphasis on diet to improve the cardiovascular (CV) risk profile has been the
      focus of many studies. Recently, virgin coconut oil (VCO) has been growing in
      popularity due to its potential CV benefits. The chemical properties and the
      manufacturing process of VCO make this oil healthier than its copra-derived
      counterpart. This review highlights the mechanism through which saturated fatty
      acids contribute to CV disease (CVD), how oils and fats contribute to the risk of
      CVD, and the existing views on VCO and how its cardioprotective effects may make
      this a possible dietary intervention in isolation or in combination with exercise
      to help reduce the burden of CVDs. 

PMID- 25387217
TI  - Clinical pharmacology of albiglutide, a GLP-1 receptor agonist.
AB  - Albiglutide is a glucagon-like peptide-1 analogue composed of tandem copies of
      modified human glucagon-like peptide-1 (7-36) coupled to recombinant human
      albumin that is approved in adults for the treatment of type 2 diabetes mellitus.
      After subcutaneous administration, albiglutide is likely primarily absorbed via
      the lymphatic circulation, with maximum concentrations being reached in 3 to 5
      days; steady-state exposures are achieved following approximately 4 to 5 weeks of
      once-weekly administration. The elimination half-life of albiglutide is
      approximately 5 days. Clearance of albiglutide is 67 mL/h with between-subject
      variability of 34.9%; no covariates have been identified that would require dose
      adjustment of albiglutide. Albiglutide lowers the fasting plasma glucose and
      reduces postprandial glucose excursions. In addition, beta-cell secretion is
      enhanced by albiglutide during hyperglycemia, whereas secretion is suppressed
      during hypoglycemia; alpha-cell response to hypoglycemia is not impaired by
      albiglutide. Albiglutide does not prolong the corrected QT interval but has a
      modest effect on heart rate in patients with type 2 diabetes mellitus. Dose
      adjustment is not suggested in patients with renal impairment, but experience in
      patients with severe renal impairment is very limited, and it is recommended that
      albiglutide be used with care in such patients due to an increased frequency of
      diarrhea, nausea, and vomiting. No clinically relevant drug interactions have
      been observed in clinical trials. TRIAL REGISTRATION: NCT00938158, NCT01406262,
      NCT00537719, NCT01077505, NCT01147731, NCT01147718, NCT01147692, NCT00354536,
      NCT00394030, NCT00530309, NCT01357889, NCT00518115, NCT01098461, NCT01475734,
      NCT00849017, NCT00838916, NCT00839527, NCT01098539.

PMID- 25387218
TI  - The traditions and risks of fasting for lipid profiles in patients with diabetes.
AB  - Fasting overnight has been traditionally recommended by clinicians when ordering
      laboratory tests for lipid profiles for the purposes of health screening or
      monitoring of the effects of lipid-lowering medications. Patients with diabetes
      are tested for lipid profiles at least annually. This deeply rooted tradition of
      fasting for lipid testing has recently been challenged. Several studies have
      shown little benefit obtained by testing lipids in fasting compared with
      postprandial states. Furthermore, recent studies have shown the importance of
      postprandial lipid spikes in the pathogenesis of cardiovascular disease. At the
      same time, recent reports have alerted the medical community to the risk of
      hypoglycemia in patients with diabetes on antidiabetic medications (particularly
      insulin and sulfonylureas) who are asked to fast for lab tests. This article
      reviews the literature on these emerging issues in lipid testing in patients with
      diabetes, and offers recommendations for lipid testing in these patients in view
      of these emerging discussions. 

PMID- 25387219
TI  - Drugs and acute porphyrias: reasons for a hazardous relationship.
AB  - The porphyrias are a group of metabolic diseases caused by inherited or acquired
      enzymatic deficiency in the metabolic pathway of heme biosynthesis.
      Simplistically, they can be considered as storage diseases, because the partial
      enzymatic defect gives rise to a metabolic "bottleneck" in the biosynthetic
      pathway and hence to an accumulation of different metabolic intermediates,
      potentially toxic and responsible for the various (cutaneous or neurovisceral)
      clinical manifestations observed in these diseases. In the acute porphyrias
      (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria,
      and the very rare delta-aminolevulinic acid dehydratase ALAD-d porphyria), the
      characteristic severe neurovisceral involvement is mainly ascribed to a tissue
      accumulation of delta-aminolevulinic acid, a neurotoxic nonporphyrin precursor.
      Many different factors, both endogenous and exogenous, may favor the accumulation
      of this precursor in patients who are carriers of an enzymatic defect consistent
      with an acute porphyria, thus contributing to trigger the serious (and
      potentially fatal) clinical manifestations of the disease (acute porphyric
      attacks). To date, many different drugs are known to be able to precipitate an
      acute porphyric attack, so that the acute porphyrias are also considered as
      pharmacogenetic or toxygenetic diseases. This article reviews the different
      biochemical mechanisms underlying the capacity of many drugs to precipitate a
      porphyric acute attack (drug porphyrogenicity) in carriers of genetic mutations
      responsible for acute porphyrias, and addresses the issue of prescribing drugs
      for patients affected by these rare, but extremely complex, diseases. 

PMID- 25387220
TI  - Treating a transgender patient: overview of the guidelines.
AB  - Transgenderism and gender dysphoria are becoming more prevalent diagnoses and the
      patient population is increasing. Primary care practitioners, endocrinologists,
      and mental health professionals are all part of the medical care team that treats
      these patients, but family and internal medicine physicians continue to deliver
      the care in the long term. Transgender medicine is not a strong part of the
      medical curriculum, and recent studies have shown there is anxiety in new
      physicians in taking care of these patients. There are many aspects to
      transgender care that involve different specialities, including, but not limited
      to, mental health, primary care, endocrinology, surgery, and obstetrics and
      gynecology. This article gives an overview of the current guidelines for
      standards of care of transgender patients as delineated by the World Professional
      Association for Transgender Health and the Endocrine Society. 

PMID- 25387221
TI  - Risks and responsibilities in prescribing opioids for chronic noncancer pain,
      part 2: best practices.
AB  - Opioids are increasingly prescribed to provide effective therapy for chronic
      noncancer pain, but increased use also means an increased risk of abuse. Primary
      care physicians treating patients with chronic noncancer pain are concerned about
      adverse events and risk of abuse and dependence associated with opioids, yet many
      prescribers do not follow established guidelines for the use of these agents,
      either through unawareness or in the mistaken belief that urine toxicology
      testing is all that is needed to monitor compliance and thwart abuse. Although
      there is no foolproof way to identify an abuser and prevent abuse, the best way
      to minimize the risk of abuse is to follow established guidelines for the use of
      opioids. These guidelines entail a careful assessment of the patient, the painful
      condition to be treated, and the estimated level of risk of abuse based on
      several factors: history of abuse and current or past psychiatric disorders;
      design of a therapeutic regimen that includes both pharmacotherapeutic and
      nonpharmacologic modalities; a formal written agreement with the patient that
      defines treatment expectations and responsibilities; selection of an appropriate
      agent, including consideration of formulations designed to deter tampering and
      abuse; initiation of treatment at a low dosage with titration in gradual
      increments as needed to achieve effective analgesia; regular reassessment to
      watch for signs of abuse, to perform drug monitoring, and to adjust medication as
      needed; and established protocols for actions to be taken in case of suspected
      abuse. By following these guidelines, physicians can prescribe opioids to provide
      effective analgesia while reducing the likelihood of abuse. 

PMID- 25387222
TI  - Molecular targets in the treatment of non-small-cell lung cancer: is there hope
      on the horizon?
AB  - Non-small-cell lung cancer (NSCLC) is a growing concern worldwide, and its
      incidence continues to increase in developing countries. It has a strong
      association with smoking. Lung cancer remains the leading cause of cancer-related
      deaths in most industrialized countries and in the United States. In the last 10
      years, there have been significant advancements in the understanding of molecular
      oncogenes and how they play a role in driving lung cancer to both grow and
      metastasize. Understanding this rapidly expanding field has the potential to
      extend life, and it is an important field for all providers to conceptualize if
      they are treating patients with lung cancer. Currently, > 50% of all NSCLC is
      linked to 1 of several known genetic driver mutations. Using online databases,
      expert opinion, and practice-changing trials, we review the current standards of
      molecular testing of NSCLC and the expanding evidence of oncogenic drivers in
      nonsquamous NSCLC. 

PMID- 25387224
TI  - It takes the right medications to prevent a million heart attacks and strokes.

PMID- 25387225
TI  - Benzimidazole derivatives: selective fluorescent chemosensors for the picogram
      detection of picric acid.
AB  - 1,3,5-Tri(1H-benzo[d]imidazol-2-yl)benzene derivatives, as a new kind of
      fluorescent chemosensor for the detection of nitroaromatic explosives, are
      designed and synthesized by simple N-hydrocarbylation. Among 16 obtained
      compounds, compound 4g has the best capability for detection of picric acid (PA),
      having good selectivity and high sensitivity. The detection of PA with 4g
      solution-coated paper strips at the picogram level is developed. A simple,
      portable, and low-cost method is provided for detecting PA in solution and
      contact mode. 

PMID- 25387223
TI  - Testosterone supplementation therapy in the treatment of patients with metabolic
      syndrome.
AB  - Metabolic syndrome (MetS) comprises a clinical complex of patient risk factors,
      including increased waist circumference, high triglyceride levels, low high
      density lipoprotein cholesterol level, high blood pressure, and insulin
      resistance, the presence of which increases the likelihood of developing diabetes
      and cardiovascular disease. With a quarter of the American adult population
      affected, MetS and type 2 diabetes mellitus have been referred to as the most
      significant public health threats of the 21st century. Lifestyle modification and
      weight loss are recommended, however, no specific pharmacologic treatment is
      known. Given that low levels of testosterone have been implicated in the
      pathogenesis of MetS and an inverse relationship exists between circulating
      testosterone levels and the development of MetS, it is tempting to speculate that
      men with MetS may benefit from testosterone supplementation therapy. As such, our
      review examines the role of testosterone and the use of testosterone
      supplementation therapy as a treatment in men with MetS. 

PMID- 25387226
TI  - The pathway to total isomer selectivity: n-hexane conversion (reforming) on
      platinum nanoparticles supported on aluminum modified mesoporous silica (MCF-17).
AB  - When pure mesoporous silica (MCF-17) was modified with aluminum (Al modified MCF
      17), Lewis acid sites were created, but this material was inactive for the
      catalytic conversion (reforming) of n-hexane to isomers. When colloidally
      synthesized platinum nanoparticles were loaded onto traditional MCF-17, the
      catalyst showed very low activity toward isomer production. However, when Pt
      nanoparticles were loaded onto Al modified MCF-17, isomerization became the
      dominant catalytic pathway, with extremely high activity and selectivity (>90%),
      even at high temperatures (240-360  degrees C). This highly efficient catalytic
      chemistry was credited to the tandem effect between the acidic Al modified MCF-17
      and the Pt metal. 

PMID- 25387227
TI  - The influence of a market-oriented primary care reform on family physicians'
      working conditions: A qualitative study in Turkey.
AB  - BACKGROUND: Turkey has undergone a 'Health transformation programme' putting
      emphasis on the reorganization of primary care (PC) services towards a more
      market-oriented system. OBJECTIVES: To obtain a deep understanding of how family
      physicians (FPs) experienced the process of the reforms by focusing on working
      conditions. METHODS: This phenomenological and qualitative research used maximum
      variation sampling and 51 FPs were interviewed in 36 in-depth and four focus
      group interviews. RESULTS: Thematic analysis of interviews provided seven themes:
      (1) change in the professional identity of PC physicians (physician as
      businessperson); (2) transformation of the physician-patient relationship in PC
      (into a provider-customer relationship); (3) job description and workload; (4)
      interpersonal relationships; (5) remuneration of FPs, (6) uncertainty about the
      future and (7) exhaustion. Most FPs felt that the Family medicine model (FMM)
      placed more emphasis on the business function of family practice and this
      conflicted with their professional characteristics as physicians. FPs complained
      that some of their patients behaved as extremely demanding consumers.
      Continuously increasing responsibilities and extremely high workload were
      commonly reported problems. Most participants described the negative incentives
      in the performance scheme as a degrading method of punishment. The main factor
      was job insecurity caused by contract-based employment. FPs described the point
      at which they are with terms such as exhaustion. CONCLUSION: By increasing
      workload and creating uncertainty about the future and about income, the PC
      reforms have led to working conditions, which has led to changes in the
      professional attitudes of physicians and their practice of medicine.

PMID- 25387228
TI  - General practitioner contribution to out-of-hospital cardiac arrest outcome: A
      national registry study.
AB  - BACKGROUND: There is a wide variation in reported survival from out-of-hospital
      cardiac arrest (OHCA). One factor in this variation may be the contribution of
      general practitioners to pre-hospital resuscitation. Studies using self-reported
      data describe increased survival proportions when general practitioners are
      involved. OBJECTIVES: This study aims to investigate the contribution of general
      practitioner involvement in out-of-hospital cardiac arrest events. DESIGN AND
      SETTING: A retrospective observational study using data collected from ambulance
      records in the Republic of Ireland to describe general practitioner (GP)
      contribution to pre-hospital resuscitation attempts (n = 2369). Analysis is
      limited to patients with presumed cardiac cause and first arrest rhythm recorded
      as shockable (n = 510). RESULTS: When a GP is present at scene (n = 199) patients
      are less likely to achieve return of spontaneous circulation (ROSC) (P < 0.001)
      or be transported to hospital (P < 0.001). When GPs participate in resuscitation
      (n = 92), patients are more likely to have collapsed in a public place (P <
      0.01), receive bystander CPR (P < 0.001) and survive to hospital discharge (P <
      0.001). Multiple logistic analysis of survival suggests that GP participation in
      resuscitation increases the odds of survival (4.6; 95% CI 1.6-13.3) and having
      collapsed in a public place increases chances of survival (5.8; 95% CI 2.1-15.7).
      CONCLUSION: Our analysis suggests that in this subgroup, GP participation in OHCA
      resuscitation attempts is associated with improved patient survival. Furthermore,
      resuscitation is more likely to be ceased at scene when a GP is present,
      highlighting the role that GPs play in the compassionate management of death in
      unviable circumstances.

PMID- 25387229
TI  - Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus
      pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary
      and pancreatic carcinoma.
AB  - Background Pancreatic cancer is the fourth leading cause of cancer death for men
      and the fifth for women. The standard treatment for resectable tumours consists
      of a classic Whipple (CW) operation or a pylorus-preserving
      pancreaticoduodenectomy (PPW). It is unclear which of these procedures is more
      favourable in terms of survival, mortality, complications and quality of
      life.Objectives The objective of this systematic review is to compare the
      effectiveness of CW and PPW techniques for surgical treatment of cancer of the
      pancreatic head and the periampullary region.Search methods We conducted searches
      on 28 March 2006, 11 January 2011 and 9 January 2014 to identify all randomised
      controlled trials (RCTs),while applying no language restrictions. We searched the
      following electronic databases: 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) from The Cochrane Library
      (2013, Issue 4); MEDLINE (1946 to January 2014); and EMBASE (1980 to January
      2014). We also searched abstracts from Digestive Disease Week and United European
      Gastroenterology Week (1995 to 2010). We identified no additional studies upon
      updating the systematic review in 2014.Selection criteria We considered RCTs
      comparing CW versus PPW to be eligible if they included study participants with
      periampullary or pancreatic carcinoma. Data collection and analysis Two review
      authors independently extracted data from the included studies. We used a random
      effects model for pooling data. We compared binary outcomes using odds ratios
      (ORs), pooled continuous outcomes using mean differences (MDs) and used hazard
      ratios (HRs) for meta-analysis of survival. Two review authors independently
      evaluated the methodological quality and risk of bias of included studies
      according to the standards of The Cochrane Collaboration.Main results We included
      six RCTs with a total of 465 participants. Our critical appraisal revealed vast
      heterogeneity with respect to methodological quality and outcome parameters. In
      hospital mortality (OR 0.49, 95% confidence interval (CI) 0.17 to 1.40; P value
      0.18), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P value 0.29) and
      morbidity showed no significant differences. However, we noted that operating
      time (MD -68.26 minutes, 95% CI -105.70 to -30.83; P value 0.0004) and
      intraoperative blood loss (MD -0.76 mL, 95%CI -0.96 to -0.56; P value < 0.00001)
      were significantly reduced in the PPW group. All significant results are
      associated with low quality of evidence as determined on the basis of GRADE
      (Grades of Recommendation, Assessment, Development and Evaluation)
      criteria.Authors' conclusions No evidence suggests relevant differences in
      mortality, morbidity and survival between the two operations. Given obvious
      clinical and methodological heterogeneity, future research must be undertaken to
      perform high-quality randomised controlled trials of complex surgical
      interventions on the basis of well-defined outcome parameters.

PMID- 25387231
TI  - One hundred years of statistical developments in animal breeding.
AB  - Statistical methodology has played a key role in scientific animal breeding.
      Approximately one hundred years of statistical developments in animal breeding
      are reviewed. Some of the scientific foundations of the field are discussed, and
      many milestones are examined from historical and critical perspectives. The
      review concludes with a discussion of some future challenges and opportunities
      arising from the massive amount of data generated by livestock, plant, and human
      genome projects. 

PMID- 25387230
TI  - The impact of the milk glycobiome on the neonate gut microbiota.
AB  - Human milk is a complete source of nourishment for the infant. Exclusive
      breastfeeding not only sustains the infant's development but also guides the
      proliferation of a protective intestinal microbiota. Among the many components of
      milk that modulate the infant gut microbiota, the milk glycans, which comprise
      free oligosaccharides, glycoproteins, and glycolipids, are increasingly
      recognized as drivers of microbiota development and overall gut health. These
      glycans may display pleiotropic functions, conferring protection against
      infectious diseases and also acting as prebiotics, selecting for the growth of
      beneficial intestinal bacteria. The prebiotic effect of milk glycans has direct
      application to prevention of diseases such as necrotizing enterocolitis, a common
      and devastating disease of preterm infants. In this article, we review the impact
      of the human (and bovine) milk glycome on gut health through establishment of a
      milk-oriented microbiota in the neonate. 

PMID- 25387233
TI  - Performance of forest bryophytes with different geographical distributions
      transplanted across a topographically heterogeneous landscape.
AB  - Most species distribution models assume a close link between climatic conditions
      and species distributions. Yet, we know little about the link between species'
      geographical distributions and the sensitivity of performance to local
      environmental factors. We studied the performance of three bryophyte species
      transplanted at south- and north-facing slopes in a boreal forest landscape in
      Sweden. At the same sites, we measured both air and ground temperature. We
      hypothesized that the two southerly distributed species Eurhynchium angustirete
      and Herzogiella seligeri perform better on south-facing slopes and in warm
      conditions, and that the northerly distributed species Barbilophozia
      lycopodioides perform better on north-facing slopes and in relatively cool
      conditions. The northern, but not the two southern species, showed the predicted
      relationship with slope aspect. However, the performance of one of the two
      southern species was still enhanced by warm temperatures. An important reason for
      the inconsistent results can be that microclimatic gradients across landscapes
      are complex and influenced by many climate-forcing factors. Therefore, comparing
      only north- and south-facing slopes might not capture the complexity of
      microclimatic gradients. Population growth rates and potential distributions are
      the integrated results of all vital rates. Still, the study of selected vital
      rates constitutes an important first step to understand the relationship between
      population growth rates and geographical distributions and is essential to better
      predict how climate change influences species distributions. 

PMID- 25387234
TI  - Management of Barrett's esophagus and early esophageal cancer: update on
      endoscopic treatment strategies.
AB  - Barrett's esophagus represents the strongest known risk factor for developing
      esophageal adenocarcinoma. The traditional management strategy for identifying
      and managing Barrett's esophagus involves screening and endoscopic surveillance
      to identify early stage, curable carcinoma. Recently, endoscopic eradication
      therapy has emerged to achieve the complete eradication of Barrett's esophagus
      and intramucosal cancer to prevent the development of invasive cancer with
      lymphatic spread. Randomized trials have demonstrated the efficacy of these
      approaches to reduce the progression to cancer, and endoscopic eradication
      therapy has become the preferred treatment approach for patients with high-grade
      dysplasia, and may be utilized for management of low-grade dysplasia as well.
      Owing to excellent eradication rates and favorable side effect profile,
      radiofrequency ablation has emerged as the ablative strategy of choice for
      patients undergoing endoscopic eradication therapy.

PMID- 25387235
TI  - Dietary sodium selenite affects host intestinal and systemic immune response and
      disease susceptibility to necrotic enteritis in commercial broilers.
AB  - 1. This study was to evaluate the effects of supplementary dietary selenium (Se)
      given as sodium selenite on host immune response against necrotic enteritis (NE)
      in commercial broiler chickens. 2. Chicks were fed from hatching on a non
      supplemented diet or diets supplemented with different levels of Se (0.25, 0.50,
      and 1.00 Se mg/kg). To induce NE, broiler chickens were orally infected with
      Eimeria maxima at 14 d of age and then with Clostridium perfringens 4 d later
      using our previously established NE disease model. 3. NE-associated clinical
      signs and host protective immunity were determined by body weight changes,
      intestinal lesion scores, and serum antibodies against alpha-toxin and necrotic
      enteritis B (NetB) toxin. The effects of dietary Se on the gene expression of pro
      inflammatory cytokines e.g., interleukin (IL)-1beta, IL-6, IL-8LITAF
      (lipopolysaccharide-induced TNFalpha-factor), tumour necrosis factor (TNF) SF15,
      and inducible nitric oxide synthase (iNOS), glutathione peroxidase 7 (GPx7), and
      avian beta-defensins (AvBD) 6, 8, and 13 (following NE infection) were analysed
      in the intestine and spleen. 4. The results showed that dietary supplementation
      of newly hatched broiler chicks with 0.25 Se mg/kg from hatch significantly
      reduced NE-induced gut lesions compared with infected birds given a non
      supplemented diet. The levels of serum antibody against the NetB toxin in the
      chicks fed with 0.25 and 0.50 mg/kg Se were significantly higher than the non
      supplemented control group. The transcripts for IL-1beta, IL-6, IL-8, iNOS,
      LITAF, and GPx7, as well as AvBD6, 8, and 13 were increased in the intestine and
      spleen of Se-supplemented groups, whereas transcript for TNFSF15 was decreased in
      the intestine. 5. It was concluded that dietary supplementation with optimum
      levels of Se exerted beneficial effects on host immune response to NE and reduced
      negative consequence of NE-induced immunopathology.

PMID- 25387232
TI  - Development, regeneration, and evolution of feathers.
AB  - The feather is a complex ectodermal organ with hierarchical branching patterns.
      It provides functions in endothermy, communication, and flight. Studies of
      feather growth, cycling, and health are of fundamental importance to avian
      biology and poultry science. In addition, feathers are an excellent model for
      morphogenesis studies because of their accessibility, and their distinct patterns
      can be used to assay the roles of specific molecular pathways. Here we review the
      progress in aspects of development, regeneration, and evolution during the past
      three decades. We cover the development of feather buds in chicken embryos,
      regenerative cycling of feather follicle stem cells, formation of barb branching
      patterns, emergence of intrafeather pigmentation patterns, interplay of hormones
      and feather growth, and the genetic identification of several feather variants.
      The discovery of feathered dinosaurs redefines the relationship between feathers
      and birds. Inspiration from biomaterials and flight research further fuels
      biomimetic potential of feathers as a multidisciplinary research focal point. 

PMID- 25387236
TI  - Cytomegalovirus infection in inflammatory bowel disease is not associated with
      worsening of intestinal inflammatory activity.
AB  - BACKGROUND: Cytomegalovirus is highly prevalent virus and usually occurs in
      immunocompromised patients. The pathophysiology and treatment of inflammatory
      bowel disease often induce a state of immunosuppression. Because this, there are
      still doubts and controversies about the relationship between inflammatory bowel
      disease and cytomegalovirus. AIM: Evaluate the frequency of cytomegalovirus in
      patients with inflammatory bowel disease and identify correlations. METHODS:
      Patients with inflammatory bowel disease underwent an interview, review of
      records and collection of blood and fecal samples. The search for cytomegalovirus
      was performed by IgG and IgM blood serology, by real-time PCR in the blood and by
      qualitative PCR in feces. Results were correlated with red blood cell levels, C
      reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin
      levels for each patient. RESULTS: Among the 400 eligible patients, 249 had
      Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease,
      67 of the patients had moderate or severe disease, but 126 patients presented
      with active disease, based on the evaluation of the fecal calprotectin. In
      patients with ulcerative colitis, only 21 patients had moderate disease, but 76
      patients presented with active disease, based on the evaluation of the fecal
      calprotectin. A large majority of patients had positive CMV IgG. Overall, 10
      patients had positive CMV IgM, and 9 patients had a positive qualitative
      detection of CMV DNA by PCR in the feces. All 400 patients returned negative
      results after the quantitative detection of CMV DNA in blood by real-time PCR.
      Analyzing the 19 patients with active infections, we only found that such an
      association occurred with the use of combined therapy (anti-TNF-alpha +
      azathioprine). CONCLUSION: The findings show that latent cytomegalovirus
      infections are frequent and active cytomegalovirus infection is rare. We did not
      find any association between an active infection of CMV and inflammatory bowel
      disease activity.

PMID- 25387237
TI  - Factors associated with alcohol consumption in hepatitis B carriers: a nationwide
      study in the Republic of Korea.
AB  - This study was conducted to investigate the prevalence of alcohol consumption and
      identify the sociodemographic factors associated with alcohol consumption among
      individuals with hepatitis B virus(HBV) infection. We used data from the Korean
      National Health and Nutrition Examination Surveys, a nationwide survey conducted
      between 2007 and 2011. "Monthly alcohol consumption" was defined as having
      consumed alcohol at least once per month during the past year, and "high-risk
      alcohol consumption" was defined as having consumed alcohol twice or more per
      week and, for males, having consumed at least 60 g of alcohol on one occasion or,
      for females, having consumed at least 40 g of alcohol on more than one occasion.
      The prevalence of monthly alcohol consumption was 53.2%, and that of high-risk
      alcohol consumption was 11.8% among HBV carriers. Less education was associated
      with both monthly and high-risk alcohol consumption (OR = 1.75 [95% CI = 1.02
      3.02] for monthly alcohol consumption among those with less than a high school
      education; OR = 2.48 [95% CI = 1.19-5.17] for high-risk alcohol consumption among
      those with less than a high school education and OR = 2.02 [95% CI = 1.12-3.64]
      among those with a high school education). Additionally, smoking and being male
      increased the risk of alcohol consumption, and older age and having a normal body
      mass index decreased the risk. HBV carriers who were less educated, overweight,
      and smokers were more likely to consume alcohol or meet criteria for high-risk
      drinking. Health policies and intervention programs aimed at promoting a
      generally healthy lifestyle in HBV carriers should consider educational
      inequalities and alcohol consumption.

PMID- 25387239
TI  - Youth and young adult physical activity and body composition of young adult
      women: findings from the dietary intervention study in children.
AB  - This study prospectively investigates associations between youth moderate-to
      vigorous-intensity physical activity (MVPA) and body composition in young adult
      women using data from the Dietary Intervention Study in Children (DISC) and the
      DISC06 Follow-Up Study. MVPA was assessed by questionnaire on 5 occasions between
      the ages 8 and 18 years and at age 25-29 years in 215 DISC female participants.
      Using whole body dual-energy x-ray absorptiometry (DXA), overall adiposity and
      body fat distribution were assessed at age 25-29 years by percent body fat (%fat)
      and android-to-gynoid (A:G) fat ratio, respectively. Linear mixed effects models
      and generalized linear latent and mixed models were used to assess associations
      of youth MVPA with both outcomes. Young adult MVPA, adjusted for other young
      adult characteristics, was significantly inversely associated with young adult
      %fat (%fat decreased from 37.4% in the lowest MVPA quartile to 32.8% in the
      highest (p-trend = 0.02)). Adjusted for youth and young adult characteristics
      including young adult MVPA, youth MVPA also was significantly inversely
      associated with young adult %fat (beta=-0.40 per 10 MET-hrs/wk, p = .02) . No
      significant associations between MVPA and A:G fat ratio were observed. Results
      suggest that youth and young adult MVPA are important independent predictors of
      adiposity in young women. 

PMID- 25387238
TI  - Enhancement of resting-state fcMRI networks by prior sensory stimulation.
AB  - It is important to consider the effect of a previous experimental condition when
      analyzing resting-state functional connectivity magnetic resonance imaging
      (fcMRI) data. In this work, a simple sensory stimulation functional MRI (fMRI)
      experiment was conducted between two resting-state fcMRI acquisitions in
      anesthetized rats using a high-field small-animal MR scanner. Previous human
      studies have reported fcMRI network alteration by prior task/stimulus utilizing
      similar experimental paradigms. An anesthetized rat preparation was used to test
      whether brain regions with higher level functions are involved in post
      task/stimulus fcMRI network alteration. We demonstrate significant fcMRI
      enhancement poststimulation in the sensory cortical, limbic, and insular brain
      regions in rats. These brain regions have been previously implicated in vigilance
      and anesthetic arousal networks. We tested their experimental paradigm in several
      inbred strains of rats with known phenotypic differences in anesthetic
      susceptibility and cerebral vascular function. Brown Norway (BN), Dahl Salt
      Sensitive (SS), and consomic SSBN13 strains were tested. We have previously shown
      significant differences in blood oxygen level-dependent fMRI activity and fcMRI
      networks across these strains. Here we report statistically significant
      interstrain differences in regional fcMRI poststimulation enhancement. In the SS
      strain, poststimulation enhancement occurred in posterior sensory and limbic
      cortical brain regions. In the BN strain, poststimulation enhancement appeared in
      anterior cingulate and subcortical limbic brain regions. These results imply that
      a prior condition has a significant impact on fcMRI networks that depend on
      intersubject difference in genetics and physiology.

PMID- 25387240
TI  - A new exploration for gallbladder polyps: gallbladder polypectomy by endolap
      technique.
AB  - Abstract Gallbladder polyps are most commonly treated with cholecystectomy, which
      is associated with various complications. For benign disease, preserving the
      gallbladder is preferable. Since 1994, we have been exploring percutaneous
      polypectomy and have recently developed an improved new technique. This study
      reports a new endoscopic-laparoscopic (Endolap) technique for the removal of
      polyps and the preservation of the gallbladder. Nine Chinese mini-pigs were used
      to observe mucosal regeneration. Microwaves of 50-70 mA for 9 seconds were safe,
      and the gallbladder mucosa of pigs recovered to nearly normal 2 weeks later. In
      the clinical cases, 60 patients with gallbladder polyps were studied. With the
      patient under general anesthesia, each polyp stem was coagulated, and then the
      polyp was removed. All procedures were successful at between 60 and 135 minutes.
      The success rate was 93.33% (56/60). A retrospective analysis was conducted to
      assess the recovery of gallbladder function. All patients were followed up and
      symptom-free, without recurrence of the polyps; 3 months after the operation, the
      volume and contraction of the gallbladder recovered to preoperative levels. Thus
      the Endolap technique is reliable for removing benign gallbladder polyps and is
      applicable to a wider range of clinical situations than percutaneous polypectomy.

PMID- 25387241
TI  - Ionic liquids at nonane-water interfaces: molecular dynamics studies.
AB  - The structures of ternary systems with water, nonane, and an ionic liquid, with
      the ionic liquid placed between water and nonane, have been studied using
      atomistic molecular dynamics simulations. Three different ionic liquids with 1-n
      butyl-3-methylimidazolium cation and bromide, tetrafluoroborate, and
      trifluoromethanesulfonate anions have been studied. The ionic liquids disperse
      into the aqueous phase quickly and are solubilized in water within 15 ns to form
      two equivalent nonane-aqueous ionic liquid interfaces. The interfacial region is
      enriched with ionic liquids due to the amphiphilicity of the cations. The
      presence of ionic liquids at the interface reduces the interfacial tension
      between the nonane and water, thus facilitating the mixing of aqueous and nonane
      phases. The reduction in the interfacial tension is found to be inversely related
      to the solubility of the corresponding ionic liquid in water. The butyl chains of
      the cations and the trifluoromethanesulfonate anions present in the interfacial
      region are found to be preferentially oriented parallel to the interface normal. 

PMID- 25387242
TI  - Solution deposition of thin carbon coatings on LiFePO4.
AB  - We report the synthesis of ultrathin carbon coatings on polycrystalline LiFePO4
      via solution deposition and subsequent annealing. The annealing temperature was
      systematically investigated with polymer systems on LiFePO4 nanostructures. The
      crystal structures, sizes, and morphologies were monitored and analyzed by X-ray
      diffraction (XRD) and scanning electron microscopy (SEM). Micro-Raman and TEM
      were used to interrogate the carbon coatings after heat-treatments.
      Electrochemical performance of coated materials was investigated by cyclic
      voltammograms (CVs) and galvanostatic charge-discharge analysis. The olivine
      structured LiFePO4 remained stable up to 600  degrees C but underwent a rapid
      reduction reaction from LiFePO4 to Fe2P above 700  degrees C. The good
      compatibility between polyethylene glycol (PEG) and the surface of LiFePO4
      enabled the formation of core-shell structure, which was transformed into a thin
      carbon coating on LiFePO4 after annealing. Both PEG and sucrose carbon-based
      sources yielded high-quality carbon coatings after annealing, as determined by
      the graphitic/disordered (G/D) ratios of 1.30 and 1.20, respectively. By
      producing more uniform and coherent coatings on LiFePO4 particles, batteries with
      significantly less carbon (i.e., 0.41 wt %) were fabricated and demonstrated
      comparable performance to traditionally synthesized carbon-coated LiFePO4 with
      higher carbon loadings (ca. 2.64 wt %). This will enable development of batteries
      with higher active material loading and therefore significantly larger energy
      densities.

PMID- 25387243
TI  - CentrinFish permit the visualization of centrosome dynamics in a cellular context
      in vivo.

PMID- 25387244
TI  - Herpes simplex virus type 2 among mobile pastoralists in northwestern Namibia.
AB  - BACKGROUND: Although herpes simplex virus type 2 (HSV-2) epidemiology has been
      described for many western and/or urban populations, disease burden has not been
      characterized for remote, non-western, under treated populations, where patterns
      of risk and vulnerability may be very different. AIMS: To understand demographic,
      behavioural and geographic influences on risk for HSV-2 in a population of
      mobile, rural pastoralists in northwestern Namibia. SUBJECTS AND METHODS: The
      authors conducted a cross-sectional survey of reproductively aged adults (n =
      445) across 28 villages in Kaokoveld, Namibia. All participants completed a
      questionnaire of demographic data, ecological interactions and sexual behaviour,
      and a rapid test specific for HSV-2. RESULTS: HSV-2 status was significantly
      associated with being female (OR = 3.1, 95% CI = 2.00, 4.71), increasing age
      (men: OR = 7.5, 95% CI = 2.67, 20.85; women: OR = 6.2, 95% CI = 2.48, 15.50) and
      with higher wealth among men (OR = 5.1, 95% CI = 1.98, 13.09). CONCLUSIONS:
      Higher risk among women can be explained, in part, by local hygiene practices and
      a preference for "dry" sex. There was considerable variation in prevalence by
      region, which appears to be linked to geographic remoteness. Culturally
      contextualized epidemiologic studies of remote, vulnerable populations can
      provide essential information for limiting the introduction and spread of new
      infections.

PMID- 25387245
TI  - Allele frequencies for 13 STRs loci in a Western Anatolia population and their
      forensic evaluation.
AB  - BACKGROUND: Numerous studies demonstrated that STRs have become powerful tools in
      forensic case work. AIM: To profile DNA samples from 104 Turkish males for 13
      autosomal, STR markers intended for human identification purposes and to estimate
      the allele frequency distribution in forensic cases in a Turkish population.
      SUBJECTS AND METHODS: Thirteen autosomal STR loci, namely D3S1358, D2S1338,
      D16S539, D8S1179, D21S11, D18S51, TH01, D13S317, D7S820, CSF1PO, TPOX, D5S818 and
      FGA, were analysed in a sample of 104 healthy and unrelated Turkish individuals
      who have been living in the city of Izmir. All loci were amplified by using
      AmpFlSTR Identifier Kit. Genetic analysis was carried out on an ABI PRISM 310
      Genetic Analyser. RESULTS: For each locus, 6-15 alleles were found with
      frequencies ranging from 0.005-0.514 and heterozygosities ranging from 0.686
      0.868. The PIC value was highly significant (0.999). CONCLUSION: The 13 STR loci
      in the AmpFlSTR Identifier Kit are suitable for forensic identification and
      paternity tests due to high heterozygosity. The observed PD value is sufficiently
      high for human identification purposes. In conclusion, the 13 STR loci seem to be
      useful markers for personal identification and forensic case work in the Turkish
      population. The results also demonstrate the importance of region-specific
      studies.

PMID- 25387246
TI  - Nitration of Y10 in Abeta1-40: is it a compensatory reaction against
      oxidative/nitrative stress and Abeta aggregation?
AB  - Amyloid beta peptide (Abeta) aggregation is considered to be a crucial
      pathological biomarker of Alzheimer's disease (AD). It was found that Abeta and
      heme can form an Abeta-heme complex, which results in increased heme
      pseudoperoxidase activity. Recently, we found that increasing pseudoperoxidase
      activity induces elevated tyrosine nitration on Abeta in the presence of nitrite
      and hydrogen peroxide. However, the nature of tyrosine nitration of Abeta and its
      physiologic significance are still unknown. In this study, we revealed that
      Abeta1-40 can be nitrated in vitro by binding to heme in the presence of nitrite
      and hydrogen peroxide. Moreover, we found that tyrosine nitration had little
      effect on Abeta1-40's binding activity with heme. A TMB assay also revealed that
      the peroxidase activity of the heme-Abeta1-40Y10(3N)T (tyrosine 10 was replaced
      with 3-nitrtotyrosine in Abeta1-40) complex was moderately increased compared
      with that of the heme-Abeta1-40 complex. Furthermore, Thioflavin T fluorescence
      and transmission electron microscopic characterization indicated that tyrosine
      nitration significantly decreased the aggregation of Abeta1-40. In addition, a
      cytotoxicity test verified that wild-type Abeta1-40 was more cytotoxic than that
      of Abeta1-40Y10(3N)T. These results suggest that nitration of Abeta1-40 might be
      an Abeta detoxicant process and a compensatory reaction to nitrative stress. Our
      findings may lead to a detailed understanding of the function of Abeta1-40 and
      may be helpful in preventing and curing AD. 

PMID- 25387247
TI  - TRPV1 channels are involved in niacin-induced cutaneous vasodilation in mice.
AB  - Niacin is effective in treating dyslipidemias but causes cutaneous vasodilation
      or flushing, a side effect that limits its clinical use. Blocking prostaglandins
      in humans reduces but does not consistently eliminate flushing, indicating
      additional mechanisms may contribute to flushing. The transient receptor
      potential vanilloid 1 (TRPV1) channel, when activated, causes cutaneous
      vasodilation and undergoes tachyphylaxis similar to that seen with niacin. Using
      a murine model, early phase niacin-induced flushing was examined and TRPV1
      channel involvement demonstrated using pharmacologic blockade, desensitization,
      and genetic knockouts (TRPV1 KO). The TRPV1 antagonist AMG9810 reduced the
      magnitude of the initial and secondary peaks and the rapidity of the vasodilatory
      response (slope). TRPV1 desensitization by chronic capsaicin reduced the initial
      peak and slope. TRPV1 KO mice had a lower initial peak, secondary peak, and slope
      compared with wild-type mice. Chronic niacin reduced the initial peak, secondary
      peak, and slope in wild-type mice but had no effect in knockout mice.
      Furthermore, chronic niacin diminished the response to capsaicin in wild-type
      mice. Overall, these data demonstrate an important role for TRPV1 channels in
      niacin-induced flushing, both in the acute response and with chronic
      administration. That niacin-induced flushing is a complex cascade of events,
      which should inform pharmacological intervention against this side effect.

PMID- 25387249
TI  - FoCa: a modular treatment planning system for proton radiotherapy with research
      and educational purposes.
AB  - FoCa is an in-house modular treatment planning system, developed entirely in
      MATLAB, which includes forward dose calculation of proton radiotherapy plans in
      both active and passive modalities as well as a generic optimization suite for
      inverse treatment planning. The software has a dual education and research
      purpose. From the educational point of view, it can be an invaluable teaching
      tool for educating medical physicists, showing the insights of a treatment
      planning system from a well-known and widely accessible software platform. From
      the research point of view, its current and potential uses range from the fast
      calculation of any physical, radiobiological or clinical quantity in a patient CT
      geometry, to the development of new treatment modalities not yet available in
      commercial treatment planning systems. The physical models in FoCa were compared
      with the commissioning data from our institution and show an excellent agreement
      in depth dose distributions and longitudinal and transversal fluence profiles for
      both passive scattering and active scanning modalities. 3D dose distributions in
      phantom and patient geometries were compared with a commercial treatment planning
      system, yielding a gamma-index pass rate of above 94% (using FoCa's most accurate
      algorithm) for all cases considered. Finally, the inverse treatment planning
      suite was used to produce the first prototype of intensity-modulated, passive
      scattered proton therapy, using 13 passive scattering proton fields and multi
      leaf modulation to produce a concave dose distribution on a cylindrical solid
      water phantom without any field-specific compensator.

PMID- 25387248
TI  - Flavonols in the Prevention of Diabetes-induced Vascular Dysfunction.
AB  - As flavonols are present in fruits and vegetables, they are consumed in
      considerable amounts in the diet. There is growing evidence that the well
      recognized antioxidant, anti-inflammatory, and vasorelaxant actions of flavonols
      may, at least in part, result from modulation of biochemical signaling pathways
      and kinases. It is well established that diabetes is associated with increased
      cardiovascular morbidity and mortality. Despite clinical management of blood
      glucose levels, diabetes often results in cardiovascular disease. There is good
      evidence that endothelial dysfunction contributes significantly to the
      progression of diabetic cardiovascular diseases. This review describes the
      biological actions of flavonols that may ameliorate adverse cardiovascular events
      in diabetes. We discuss evidence that flavonols may be developed as novel
      pharmacological agents to prevent diabetes-induced vascular dysfunction. 

PMID- 25387250
TI  - Small airway epithelial cells exposure to printer-emitted engineered
      nanoparticles induces cellular effects on human microvascular endothelial cells
      in an alveolar-capillary co-culture model.
AB  - The printer is one of the most common office equipment. Recently, it was reported
      that toner formulations for printing equipment constitute nano-enabled products
      (NEPs) and contain engineered nanomaterials (ENMs) that become airborne during
      printing. To date, insufficient research has been performed to understand the
      potential toxicological properties of printer-emitted particles (PEPs) with
      several studies using bulk toner particles as test particles. These studies
      demonstrated the ability of toner particles to cause chronic inflammation and
      fibrosis in animal models. However, the toxicological implications of inhalation
      exposures to ENMs emitted from laser printing equipment remain largely unknown.
      The present study investigates the toxicological effects of PEPs using an in
      vitro alveolar-capillary co-culture model with Human Small Airway Epithelial
      Cells (SAEC) and Human Microvascular Endothelial Cells (HMVEC). Our data
      demonstrate that direct exposure of SAEC to low concentrations of PEPs (0.5 and
      1.0 ug/mL) caused morphological changes of actin remodeling and gap formations
      within the endothelial monolayer. Furthermore, increased production of reactive
      oxygen species (ROS) and angiogenesis were observed in the HMVEC. Analysis of
      cytokine and chemokine levels demonstrates that interleukin (IL)-6 and MCP-1 may
      play a major role in the cellular communication observed between SAEC and HMVEC
      and the resultant responses in HMVEC. These data indicate that PEPs at low, non
      cytotoxic exposure levels are bioactive and affect cellular responses in an
      alveolar-capillary co-culture model, which raises concerns for potential adverse
      health effects. 

PMID- 25387251
TI  - Consumer exposures to laser printer-emitted engineered nanoparticles: A case
      study of life-cycle implications from nano-enabled products.
AB  - It is well established that printers emit nanoparticles during their operation.
      To-date, however, the physicochemical and toxicological characterization of "real
      world" printer-emitted nanoparticles (PEPs) remains incomplete, hampering proper
      risk assessment efforts. Here, we investigate our earlier hypothesis that
      engineered nanomaterials (ENMs) are used in toners and ENMs are released during
      printing (consumer use). Furthermore, we conduct a detailed physicochemical and
      morphological characterization of PEPs in support of ongoing toxicological
      assessment. A comprehensive suite of state of the art analytical methods and
      tools was employed for the physicochemical and morphological characterization of
      11 toners widely utilized in printers from major printer manufacturers and their
      PEPs. We confirmed that a number of ENMs incorporated into toner formulations
      (e.g. silica, alumina, titania, iron oxide, zinc oxide, copper oxide, cerium
      oxide, carbon black among others) and released into the air during printing. All
      evaluated toners contained large amounts of organic carbon (OC, 42-89%),
      metals/metal oxides (1-33%), and some elemental carbon (EC, 0.33-12%). The PEPs
      possess a composition similar to that of toner and contained 50-90% OC, 0.001
      0.5% EC and 1-3% metals. While the chemistry of the PEPs generally reflected that
      of their toners, considerable differences are documented indicative of potential
      transformations taking place during consumer use (printing). We conclude that:
      (i) Routine incorporation of ENMs in toners classifies them as nano-enabled
      products (NEPs); (ii) These ENMs become airborne during printing; (iii) The
      chemistry of PEPs is complex and it reflects that of the toner and paper. This
      work highlights the importance of understanding life-cycle (LC) nano-EHS
      implications of NEPs and assessing real world exposures and associated
      toxicological properties rather than focusing on "raw" materials used in the
      synthesis of an NEP. 

PMID- 25387252
TI  - Both released silver ions and particulate Ag contribute to the toxicity of AgNPs
      to earthworm Eisenia fetida.
AB  - To disentangle the contribution of ionic and nanoparticulate Ag to the overall
      toxicity to the earthworm Eisenia fetida, a semi-permeable membrane strategy was
      used to separate Ag(+) released from silver nanoparticles (AgNPs) in an aqueous
      exposure. Internal Ag fractionation, activities of antioxidant enzymes and
      metabolites in E. fetida were determined after 96 h of exposure to two sizes of
      polyvinylpyrrolidone-coated AgNPs. The response of the antioxidant system
      combined with the content of malondialdehyde indicated that the Ag(+) released
      from AgNPs induced significant oxidative stress to the earthworms. Ag accumulated
      from AgNPs was predominantly associated with the granules and cell membrane
      compartments, whereas dissolved Ag was localized in the cytosol-containing
      fraction. In both Ag(+) exposures, two intermediates in the Krebs cycle,
      succinate and fumarate, were significantly elevated and depleted, respectively. A
      similar alteration pattern was seen in groups exposed to both smaller AgNPs (S
      AgNP, 10 nm) and larger AgNP (L AgNP, 40 nm), indicating that these effects in E.
      fetida were induced by exposure to released Ag(+). In addition, unique metabolic
      responses including decreased malate and glucose levels in S AgNP-exposed
      earthworms could be associated with exposure to nanoparticulate silver. Increased
      leucine and arginine and decreased ATP and inosine levels were observed in L AgNP
      exposures only, which clearly demonstrated a size-specific effect of AgNPs.
      Collectively, this study provided strong evidence that nanosilver acts by a
      different mechanism than ionic silver to cause acute toxicity to E. fetida, but
      further verification under different environmental conditions is needed. 

PMID- 25387253
TI  - Assessment of the developmental toxicity of nanoparticles in an ex vivo 3D model,
      the murine limb bud culture system.
AB  - The rapid growth of nanotechnological products for biomedical applications has
      exacerbated the need for suitable biological tests to evaluate the potential
      toxic effects of nanomaterials. The possible consequences of exposure during
      embryo and fetal development are of particular concern. The limb bud culture is
      an ex vivo 3D model in which growth, cell differentiation, and tissue
      organization occur and both molecular and functional endpoints can be
      quantitatively assessed. We employed this model to assess biochemical and
      morphological changes induced during organogenesis by two classes of
      nanostructured materials: quantum dot nanocrystals and organic polyglycerol
      sulfate dendrimers (dPGS). We show that quantum dots carrying mercaptopropionic
      acid (QD-MPA) on the surface, commonly used in biological studies, inhibit the
      development of limb buds from CD1 wildtype and Col2a1; Col10a1; Col1a1 triple
      transgenic fluorescent reporter mice, as revealed by changes in several
      morphological and biochemical markers. QD-MPA interfere with chondrogenesis and
      osteogenesis and disrupt the expression of COL10A1 and COL1A1, key markers of
      differentiation. In contrast, equivalent (3-100 nM) concentrations of dPGS do not
      adversely affect limb development. Neither QD-MPA nor dPGS-Cy5 alters the
      expression of several markers of cell proliferation or apoptosis. Collectively,
      these results suggest that murine limb buds in culture constitute a convenient,
      inexpensive and reliable developmental model for the assessment of the
      nanotoxicological effects of nanocrystals and polymers. In these 3D cultures, any
      effect that is observed can be directly ascribed to the nanostructures per se or
      a degradation component released from the complex nanostructure. 

PMID- 25387254
TI  - Toward standardization of hair cortisol measurement: results of the first
      international interlaboratory round robin.
AB  - BACKGROUND: The importance of hair cortisol as a long-term retrospective measure
      of systemic cortisol exposure is being increasingly recognized, and over recent
      years, the field of hair cortisol analysis has seen rapid expansion with
      laboratories around the globe, integrating hair cortisol analysis into their
      study designs. These laboratories use different methods of analysis, and
      presently, no attempt has been made to compare them. To move toward clinical
      utilization of this novel method, international benchmark reference values must
      be established. For that end, 4 leading laboratories in hair cortisol testing set
      up a protocol for comparison of the methods used by them. METHODS: Four
      immunoassay methods and 2 liquid chromatograph-mass spectrometry (LC-MS/MS)
      methods were compared by analyzing the same hair samples representing the low,
      intermediate, and high ranges of hair cortisol concentrations (HCC). RESULTS: HCC
      determined by the 4 immunoassay methods were highly and positively
      intercorrelated (r(2) between 0.92 and 0.97; all P < 0.0001) in all comparisons
      of individual laboratories. Additionally, each laboratory's immunoassay HCC had
      significant positive correlations (r(2) between 0.88 and 0.97; all P < 0.0001)
      with each of the 2 LC-MS/MS methods, which produced practically identical
      results. CONCLUSIONS: This study indicates that laboratories using immunoassays
      can use a correction factor that will convert results into standard LC-MS/MS
      equivalents.

PMID- 25387255
TI  - The College of American Pathologists guidelines for whole slide imaging
      validation are feasible for pediatric pathology: a pediatric pathology practice
      experience.
AB  - Whole slide imaging (WSI) is rapidly transforming educational and diagnostic
      pathology services. Recently, the College of American Pathologists Pathology and
      Laboratory Quality Center (CAP-PLQC) published recommended guidelines for
      validating diagnostic WSI. We prospectively evaluated the guidelines to determine
      their utility in validating pediatric surgical pathology and cytopathology
      specimens. Our validation included varied pediatric specimen types, including
      complex or less common diagnoses, in accordance with the guidelines. We completed
      WSI review of 60 surgical pathology cases and attempted WSI review of 21
      cytopathology cases. For surgical pathology cases, WSI diagnoses were highly
      concordant with glass slide diagnoses; a discordant diagnosis was observed in 1
      of 60 cases (98.3% concordance). We found that nucleated red blood cells and
      eosinophilic granular bodies represented specific challenges to WSI review of
      pediatric specimens. Cytology specimens were more frequently discordant or failed
      for technical reasons, with overall concordance of 66.7%. Review of pediatric
      cytopathology specimens will likely require image capture in multiple focal
      planes. This study is the first to specifically evaluate WSI review for pediatric
      specimens and demonstrates that specimens representing the spectrum of pediatric
      surgical pathology practice can be reviewed using WSI. Our application of the
      proposed CAP-PLQC guidelines to pediatric surgical pathology specimens is, to our
      knowledge, the first prospective implementation of the CAP-PLQC guidelines. 

PMID- 25387256
TI  - Prospective study of effectiveness of ultrasound-guided radiofrequency ablation
      versus control group in patients affected by benign thyroid nodules.
AB  - CONTEXT: Ultrasound-guided radiofrequency ablation (RFA) of solid thyroid nodules
      (TNs) is a minimally invasive procedure that may induce a volume reduction of
      symptomatic solid benign TNs. OBJECTIVE: The aim of the study was to evaluate the
      effectiveness and safety of RFA in debulking benign TNs. DESIGN AND PATIENTS:
      Eighty-four consecutive patients with symptomatic and cytologically benign solid
      nodules were randomly assigned to either a single RFA session (group A; n = 42)
      or follow-up (group B; n = 42) at our center. Entry criteria were a solid thyroid
      nodule or predominantly solid (with a fluid component <= 30% of the volume),
      normal thyroid function, no autoimmunity, and no previous thyroid gland
      treatment. Three subgroups were formed according to the baseline volume of
      nodules: small (<= 12 mL), medium (from 12 to 30 mL), or large (>30 mL). METHODS:
      In group A RFA was performed in a single session with the moving-shot technique.
      Volume and local symptom changes were evaluated 1 and 6 months after RFA.
      RESULTS: In group A, the volume decreased from 24.5.5 +/- 19.6 to 8.6 +/- 9.5 6
      months after RFA (P = .001). The greatest volume reduction was in small nodules.
      The pressure symptom score improved only in medium and large nodules (P < .001),
      whereas the cosmetic score improved in all treated patients (P < .001). The rate
      of thyroid volumetric reduction was not statistically different between solid and
      predominantly solid nodules. Only one patient experienced permanent right
      paramedian vocal cord palsy with inspiratory stridor without dysphonia. In group
      B, nodule volume remained unchanged, whereas the symptom score was worse at the 6
      month evaluation (P = .01). CONCLUSIONS: RFA is effective in reducing thyroid
      nodule volume. The best reduction rate was observed in small TNs. The thyroid
      volumetric reduction does not change according to the sonographic features. The
      mean treatment duration was longer in larger TNs.

PMID- 25387257
TI  - Smoking as an effect modifier of the association of calcium intake with bone
      mineral density.
AB  - CONTEXT: Data from physiological studies suggest smoking to have detrimental
      effects on calcium absorption, but large-scale investigations of this interaction
      and its importance with respect to bone health in humans are lacking. OBJECTIVE:
      The objective of the study was to examine the potential smoking-associated effect
      heterogeneity in the relationship of dietary calcium intake with bone mineral
      density in the general population. DESIGN: This was an observational, cross
      sectional study. PARTICIPANTS: A total of 14 116 participants of the Third
      National Health and Nutrition Examination Survey, including 6882 never, 3532
      former, and 3702 current smokers. The median age of the participants was 44
      years, and 52% were female. MAIN OUTCOME MEASURE: Bone mineral density at the
      femoral neck as determined by dual-energy x-ray absorptiometry was measured.
      RESULTS: In multiple linear regression adjusting for age, sex, race/ethnicity,
      and education, the association of calcium intake with bone mineral density was
      characterized by suggestive overall positive trends in all three smoking behavior
      categories. Detailed dose-response analyses by restricted cubic spline modeling
      revealed more pronounced nonlinearity among former smokers, but the interaction
      of smoking with calcium intake on bone mineral density did not reach statistical
      significance in any of these models. The dose-response curves became even more
      homogenous across smoking behavior strata after additional adjustment for body
      mass index and physical activity. CONCLUSION: Even though the present results
      cannot rule out that smoking-associated differences in calcium absorption exist,
      they do suggest that smoking behavior does not have any relevant impact on the
      beneficial effects of calcium intake on bone mineral density at the population
      level.

PMID- 25387258
TI  - Fasting and OGTT-derived measures of insulin resistance as compared with the
      euglycemic-hyperinsulinemic clamp in nondiabetic Finnish offspring of type 2
      diabetic individuals.
AB  - CONTEXT: It remains to be established which surrogate marker is the most
      predictive of insulin resistance. OBJECTIVE: We evaluated the incremental value
      of the Matsuda insulin sensitivity index (ISI) to homeostasis model assessment of
      insulin resistance (HOMA-IR) for detecting insulin resistance. DESIGN AND
      SETTING: This was a cross-sectional analysis of the EUGENE2 Kuopio cohort.
      PARTICIPANTS: Participants included 266 nondiabetic Finnish offspring of type 2
      diabetic individuals (aged 24-50 years). MAIN OUTCOME MEASURES: Insulin
      resistance (the lowest whole-body glucose uptake quartile) was measured by the
      euglycemic-hyperinsulinemic clamp. We used the area under the receiver operating
      characteristic curve, an insensitive method to model improvement.
      Reclassification was assessed by the net reclassification improvement and
      integrated discrimination improvement. We generated four strata using, as cut
      points, the 0.05, 0.25, and 0.70 probabilities of having insulin resistance.
      These were observed probabilities at body mass index of 20, 27, and 35 kg/m(2),
      respectively. RESULTS: The area under the receiver operating characteristic curve
      of the Matsuda ISI based on 5 time points (0, 30, 60, 90, and 120 minutes) did
      not differ statistically from that of HOMA-IR (0.897 and 0.875, P = .080).
      However, the Matsuda ISI added incremental value to HOMA-IR for the detection of
      insulin-resistant individuals (net reclassification improvement, 26.2%, P < .001;
      integrated discrimination improvement, 6.3%, P < .001). A modified Matsuda ISI
      based on 4 time points (0, 30, 60, and 120 minutes) yielded similar results.
      CONCLUSION: The Matsuda ISI has additional value for the detection of insulin
      resistance beyond the ability of HOMA-IR. The Matsuda ISI reclassifies a net of
      26% of individuals more appropriately.

PMID- 25387259
TI  - Testosterone to dihydrotestosterone ratio as a new biomarker for an adverse
      metabolic phenotype in the polycystic ovary syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is a heterogeneous disease with many
      different aspects, including hyperandrogenism and metabolic disturbances.
      Clinical phenotypes show different patterns of steroid hormones that have been
      investigated to some extent. OBJECTIVE: This study intended to determine the role
      of the testosterone (TT) to dihydrotestosterone (DHT) ratio (TT/DHT ratio) in
      PCOS patients and to further assess the correlation of this ratio with hormonal,
      anthropometric, and metabolic parameters. DESIGN AND SETTING: Serum samples of
      275 premenopausal PCOS patients fulfilling Rotterdam criteria and 35 BMI-matched,
      premenopausal, healthy controls were analyzed for testosterone, DHT,
      dehydroepiandrosterone (DHEA), and androstenedione using liquid
      chromatography/mass spectrometry. MAIN OUTCOME MEASURES: We measured total levels
      of testosterone and DHT and calculated unbound hormone levels as well as the
      ratio of testosterone to DHT. Further, impaired glucose tolerance, basal and
      stimulated serum insulin levels, metabolic syndrome and insulin resistance
      according to the homeostatic model assessment (HOMA-IR) were assessed. RESULTS:
      PCOS patients showed significantly higher levels of TT (P < .001), free
      testosterone (P < .001), and free DHT (P < .001) compared to healthy controls.
      The TT/DHT ratio was significantly higher in PCOS patients (P < .001). No
      difference was found for total DHT levels (P = .072). In PCOS patients alone, the
      TT/DHT ratio was significantly higher in obese patients (P < .001) and patients
      with metabolic syndrome (P < .001), impaired glucose tolerance (IGT) (P < .001)
      or insulin resistance (P < .001). Significant correlations of the TT/DHT ratio
      with various adverse anthropometric, hormonal, lipid and liver parameters and
      parameters of glucose metabolism were found. CONCLUSION: Our data provide
      evidence for a strong link between a high TT/DHT ratio and an adverse metabolic
      phenotype in PCOS patients. This correlation was only found in PCOS patients,
      suggesting the TT/DHT ratio to be a new biomarker for an adverse metabolic
      phenotype in PCOS patients.

PMID- 25387260
TI  - Weekly versus monthly testosterone administration on fast and slow skeletal
      muscle fibers in older adult males.
AB  - CONTEXT: In older adults, loss of mobility due to sarcopenia is exacerbated in
      men with low serum T. T replacement therapy is known to increase muscle mass and
      strength, but the effect of weekly (WK) vs monthly (MO) administration on
      specific fiber types is unknown. OBJECTIVE: To determine the efficacy of WK vs MO
      T replacement on the size and functional capacity of individual fast and slow
      skeletal muscle fiber types. DESIGN, SETTING, AND PATIENTS: Subjects were
      randomized into a 5-month, double-blind, placebo-controlled trial. All subjects
      (ages, 61-71 y) were community-dwelling men who had T levels < 500 ng/dL.
      INTERVENTION: Subjects were dosed weekly for 5 months, receiving continuous T
      (WK, n = 5; 100 mg T enanthate, im injection), monthly cycled T (MO, n = 7;
      alternating months of T and placebo), or placebo (n = 7). Muscle biopsies of the
      vastus lateralis were obtained before and after treatment. MAIN OUTCOME MEASURES:
      Main outcomes for individual slow and fast fibers included fiber diameter, peak
      force (P0), rate of tension development, maximal shortening velocity, peak power,
      and Ca(2+) sensitivity. RESULTS: Both treatments increased fiber diameter and
      peak power, with WK treatment 5-fold more effective than MO in increasing type I
      fiber P0. WK effects on fiber diameter and force were 1.5-fold higher in slow
      fibers compared to fast fibers. In fast type II fibers, diameter and P0 increased
      similarly between treatments. The increased power was entirely due to increased
      fiber size and force. CONCLUSIONS: In conclusion, T replacement effects were
      fiber-type dependent, restricted to increases in cell size, P0, and peak power,
      and dependent on the paradigm selected (WK vs MO).

PMID- 25387261
TI  - C-type natriuretic peptide plasma levels are elevated in subjects with
      achondroplasia, hypochondroplasia, and thanatophoric dysplasia.
AB  - CONTEXT: C-type natriuretic peptide (CNP) is a crucial regulator of endochondral
      bone growth. In a previous report of a child with acromesomelic dysplasia,
      Maroteaux type (AMDM), caused by loss-of-function of the CNP receptor
      (natriuretic peptide receptor-B [NPR-B]), plasma levels of CNP were elevated. In
      vitro studies have shown that activation of the MAPK kinase (MEK)/ERK MAPK
      pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia,
      and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by
      activating mutations of fibroblast growth factor receptor-3, which result in
      overactivation of the MEK/ERK MAPK pathway. OBJECTIVE: The purpose of this study
      was to determine whether these syndromes exhibit evidence of CNP resistance as
      reflected by increases in plasma CNP and its amino-terminal propeptide
      (NTproCNP). DESIGN: This was a prospective, observational study. SUBJECTS:
      Participants were 63 children and 20 adults with achondroplasia, 6 children with
      hypochondroplasia, 2 children with thanatophoric dysplasia, and 4 children and 1
      adult with AMDM. RESULTS: Plasma levels of CNP and NTproCNP were higher in
      children with achondroplasia with CNP SD scores (SDSs) of 1.0 (0.3-1.4) (median
      [interquartile range]) and NTproCNP SDSs of 1.4 (0.4-1.8; P < .0005). NTproCNP
      levels correlated with height velocity. Levels were also elevated in adults with
      achondroplasia (CNP SDSs of 1.5 [0.7-2.1] and NTproCNP SDSs of 0.5 [0.1-1.0], P <
      .005). In children with hypochondroplasia, CNP SDSs were 1.3 (0.7-1.5) (P = .08)
      and NTproCNP SDSs were 1.9 (1.8-2.3) (P < .05). In children with AMDM, CNP SDSs
      were 1.6 (1.4-3.3) and NTproCNP SDSs were 4.2 (2.7-6.2) (P < .01). CONCLUSIONS:
      In these skeletal dysplasias, elevated plasma levels of proCNP products suggest
      the presence of tissue resistance to CNP.

PMID- 25387262
TI  - Changes in cortical volumetric bone mineral density and thickness, and trabecular
      thickness in lactating women postpartum.
AB  - CONTEXT: Lactation is associated with decreased areal bone mineral density
      (aBMD). Replenishment occurs especially after ceased lactation. Changes in
      volumetric bone mineral density (vBMD), microstructure, and dimensional
      parameters are unknown and may clarify the role of lactation for skeletal health.
      OBJECTIVE AND MAIN OUTCOMES: The objective of the study was to test the
      hypothesis that lactation is associated with changes in aBMD, vBMD,
      microstructure, and dimensional parameters. DESIGN: At baseline (0.5 mo after
      delivery) and 4, 12, and 18 months thereafter, bone was assessed using dual
      energy x-ray absorptiometry and high-resolution peripheral quantitative computed
      tomography. PARTICIPANTS AND SETTING: Eighty-one fair-skinned postpartum women
      and 21 controls aged 25-40 years were recruited. The completion ratio was 73%.
      Postpartum women were categorized depending on duration of lactation: 0-3.9, 4
      8.9, and 9 months or longer. RESULTS: During the first 4 months, aBMD decreased
      at several sites (geometric mean +/- SE; -0.73% +/- 0.21% to -3.98% +/- 0.76%) in
      women lactating at least 4 months. During the same time, cortical vBMD at the
      ultradistal tibia decreased in women lactating 4-8.9 months (-0.26% +/- 0.08%)
      and 9 months or longer (-0.49% +/- 0.10%). At 12 months postpartum, cortical
      thickness (>= 9 mo, -2.48% +/- 0.41%) and trabecular thickness (4-8.9 mo, -2.14%
      +/- 0.92%; >= 9 mo, -2.56% +/- 1.21%) also were lower than baseline. No decreases
      were found in women lactating less than 4 months or in controls in these
      parameters. At 18 months postpartum, both cortical vBMD (>= 9 mo, -0.77% +/-
      0.17%) and trabecular thickness (4-8.9 mo, -2.25% +/- 1.25%; >= 9 mo, -3.21% +/-
      1.41%) were lower in women with long lactation. CONCLUSIONS: Decreases in
      cortical vBMD, thickness, and trabecular thickness at the ultradistal tibia were
      found in women lactating 4 months or longer. Longer follow-up is needed to
      confirm whether women with extended lactation recover fully or whether the
      changes could potentially lead to an increased risk of fracture in later life.

PMID- 25387263
TI  - Relationship between insulin resistance and beta-cell dysfunction in
      subphenotypes of prediabetes and type 2 diabetes.
AB  - CONTEXT: There is little overlap between diabetes diagnosed by glycated
      hemoglobin (HbA1c) and blood glucose, and it is unclear which pathophysiological
      defects are captured when using HbA1c for diagnosis. OBJECTIVE: We examined and
      compared the relationship between insulin sensitivity and beta-cell function in
      different subphenotypes of prediabetes and type 2 diabetes (T2D). DESIGN,
      SETTING, AND PARTICIPANTS: A cross-sectional analysis of the Danish ADDITION-PRO
      study was performed (n = 1713). Participants without known diabetes were
      classified into subgroups of prediabetes and T2D based on fasting or 2-hour
      glucose criteria or HbA1c. Insulin sensitivity and insulin release were
      determined from glucose and insulin concentrations during the oral glucose
      tolerance test, and disposition indices were calculated. RESULTS: Individuals
      with prediabetes or T2D diagnosed by fasting glucose had lower absolute insulin
      release (P <= .01) and higher insulin sensitivity in response to glucose intake
      (P <= .01) but a similar disposition index (P >= .36), compared with individuals
      with elevated 2-hour glucose concentrations. Individuals with HbA1c-defined T2D
      or prediabetes had a mixture of the pathophysiological defects observed in the
      glucose-defined subgroups, and individuals with normoglycemia by HbA1c had worse
      pathophysiological abnormalities than individuals with normoglycemia by the
      glucose criteria. CONCLUSIONS: On average, the diagnostic HbA1c criteria for
      diabetes and prediabetes identified individuals with a mixture of the
      pathophysiological characteristics found when using the glucose criteria, but the
      diversity and pathophysiology captured by the oral glucose tolerance test cannot
      be captured when applying the more simple HbA1c criteria. Whether the disease
      progression and prognosis will differ in individuals diagnosed by fasting
      glucose, 2-hour glucose, or HbA1c should be examined in longitudinal studies.

PMID- 25387264
TI  - Type V OI primary osteoblasts display increased mineralization despite decreased
      COL1A1 expression.
AB  - CONTEXT: Patients with type V osteogenesis imperfecta (OI) are heterozygous for a
      dominant IFITM5 c.-14C>T mutation, which adds five residues to the N terminus of
      bone-restricted interferon-induced transmembrane-like protein (BRIL), a
      transmembrane protein expressed in osteoblasts. Type V OI skeletal findings
      include hyperplastic callus formation, ossification of the forearm interosseous
      membrane, and dense metaphyseal bands. OBJECTIVE: The objective of this study was
      to examine the role of osteoblasts in the active mineralization traits of type V
      OI and the effect of the IFITM5 mutation on type I collagen. METHODS: We
      identified eight patients with the IFITM5 c.-14C>T mutation. Cultured osteoblasts
      from type V OI patients were used to study osteoblast differentiation and
      mineralization. RESULTS: We verified the expression and stability of mutant
      IFITM5 transcripts. In differentiated type V OI primary osteoblasts in culture,
      the IFITM5 expression and BRIL level is comparable with control. Both early and
      late markers of osteoblast differentiation are increased in type V OI
      osteoblasts. Mineralization, assayed by alizarin red staining, was increased in
      type V OI osteoblasts compared with control. However, type V OI osteoblasts have
      significantly decreased COL1A1 transcripts in mid- to late differentiation. Type
      I collagen protein is concomitantly decreased, with decreased cross-linked
      collagen in matrix and altered appearance of fibrils deposited in culture.
      CONCLUSIONS: This study demonstrates that type V OI mineralization has a gain-of
      function mechanism at the osteoblast level, which likely underlies the overactive
      tissue mineralization seen in patients. Decreased type I collagen expression,
      secretion, and matrix incorporation establish type V OI as a collagen-related
      defect.

PMID- 25387266
TI  - Tuning the luminescence behaviors of a chloroplatinum(II) complex by component
      exchanges of dynamic acylhydrazone bonds.
AB  - A cationic chloroplatinum(II) complex was found to show remarkable luminescence
      enhancement upon self-assembly with tripodal dynamic acylhydrazone-bridged
      sulfonates in water. The successive exchange reactions with acylhydrazine or
      aldehyde resulted in a controllable decrease in the luminescence intensities.

PMID- 25387265
TI  - Whole-exome sequencing studies of parathyroid carcinomas reveal novel PRUNE2
      mutations, distinctive mutational spectra related to APOBEC-catalyzed DNA
      mutagenesis and mutational enrichment in kinases associated with cell migration
      and invasion.
AB  - CONTEXT: Cell division cycle 73 (CDC73), encoding the protein parafibromin, is
      the most prevalent mutated gene in familial and sporadic parathyroid carcinoma
      (PC). OBJECTIVE: To identify additional genetic abnormalities in PCs. DESIGN:
      Whole-exome sequencing was performed using DNA from seven pairs of matched PCs
      and one triplet containing double primary tumor and normal leukocyte. Somatic
      variants were confirmed using Sanger sequencing and recurrently mutated genes
      were assessed in 13 additional PCs as well as 40 parathyroid adenomas (PA).
      RESULTS: PC had an average of 51 somatic variants/tumor (range 3-176) with
      approximately 58% of variants occurring as nonsynonymous single nucleotide
      variants. The importance of CDC73 in PC is reinforced with a remarkable
      preferential amplification of the mutant CDC73 allele. Furthermore, recurrent
      germ line and somatic mutations in prune homolog 2 [Drosophila] (PRUNE2) were
      found in PC and computationally predicted to be deleterious; in addition,
      recurrent mutations in kinase genes related to cell migration and invasion were
      found. PRUNE2 showed recurrent mutations in 18% (4/22) of PCs with additional
      screening in 40 PAs revealing only one rare missense polymorphism (Asp1677Asn).
      For the first time, the mutational signature associated with apolipoprotein B
      mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-catalyzed cytosine-to
      uracil deamination is found in a subset of PC. CONCLUSION: This study outlines
      the genetic landscape of PC and attempts to characterize the mutational processes
      shaping the PC genome.

PMID- 25387267
TI  - Changes in body size and physical characteristics of South African under-20 rugby
      union players over a 13-year period.
AB  - This study compared changes in the body size and physical characteristics of
      South African under-20 rugby union players over a 13-year period. A total of 453
      South African under-20 players (forwards: n = 256 and backs: n = 197) underwent
      measurements of body mass, stature, muscular strength, endurance, and 10- and 40
      m sprint times. A 2-way analysis of variance was used to determine significant
      differences for the main effects of position (forwards vs. backs) and time (1998
      2010). The pooled data showed that forwards were significantly heavier (22%),
      taller (5%), and stronger (18%) than the backs. However, when 1 repetition
      maximum strength scores were adjusted for body mass, backs were stronger per kg
      body mass. Stature did not change over the 13-year period for both groups. There
      were, however, significant increases in muscular strength (50%), body mass (20%),
      and muscular endurance (50%). Furthermore, an improvement in sprint times over 40
      (4%) and 10 m (7%) was evident over the period of the study. In conclusion, the
      players became heavier, stronger, taller, and improved their upper-body muscular
      endurance over the 13 years of the study. Furthermore, sprint times over 10 and
      40 m improved over the same time period despite the increase in body mass. It can
      be speculated that the changes in physical characteristics of the players over
      time are possibly a consequence of (a) adaptations to the changing demands of the
      game and (b) advancements in training methods.

PMID- 25387268
TI  - Analysis of subpocket selectivity and identification of potent selective
      inhibitors for matriptase and matriptase-2.
AB  - We studied the factors affecting the selectivity of peptidomimetic inhibitors of
      the highly homologous proteases matriptase and matriptase-2 across subpockets
      using docking simulations. We observed that the farther away a subpocket is
      located from the catalytic site, the more pronounced its role in selectivity. As
      a result of our exhaustive virtual screening, we biochemically validated novel
      potent and selective inhibitors of both enzymes. 

PMID- 25387270
TI  - Hearth and campfire influences on arterial blood pressure: defraying the costs of
      the social brain through fireside relaxation.
AB  - The importance of fire in human evolutionary history is widely acknowledged but
      the extent not fully explored. Fires involve flickering light, crackling sounds,
      warmth, and a distinctive smell. For early humans, fire likely extended the day,
      provided heat, helped with hunting, warded off predators and insects, illuminated
      dark places, and facilitated cooking. Campfires also may have provided social
      nexus and relaxation effects that could have enhanced prosocial behavior.
      According to this hypothesis, calmer, more tolerant people would have benefited
      in the social milieu via fireside interactions relative to individuals less
      susceptible to relaxation response. Using a randomized crossover design that
      disaggregated fire's sensory properties, pre-posttest blood pressure measures
      were compared among 226 adults across three studies with respect to viewing
      simulated muted-fire, fire-with-sound, and control conditions, in addition to
      tests for interactions with hypnotizability, absorption, and prosociality.
      Results indicated consistent blood pressure decreases in the fire-with-sound
      condition, particularly with a longer duration of stimulus, and enhancing effects
      of absorption and prosociality. Findings confirm that hearth and campfires induce
      relaxation as part of a multisensory, absorptive, and social experience.
      Enhancements to relaxation capacities in the human social brain likely took place
      via feedback involving these and other variables. 

PMID- 25387271
TI  - Impact of changing rectal dose volume parameters over time on late rectal and
      urinary toxicity after high-dose intensity-modulated radiotherapy for prostate
      cancer: A 10-years single centre experience.
AB  - BACKGROUND: External beam radiotherapy is an excellent treatment for patients
      with prostate cancer (PC). Assessing long-term radiotherapy-induced toxicity is
      important. We evaluated the impact of implementing different rectal dose volume
      constraints (DVC) on late rectal and urinary toxicity. MATERIAL AND METHODS: Six
      hundred and thirty-seven PC patients were treated with high-dose intensity
      modulated radiotherapy (IMRT) in the primary (median dose of 78 Gy to the
      prostate) or postoperative setting [median dose of 74 (adjuvant) and 76 Gy
      (salvage) to the prostatic bed]. Three groups were defined according to different
      DVC applied over time. The incidence of late rectal and urinary toxicity was
      evaluated. Three-year actuarial risk estimations of grade 2-3 rectal and urinary
      toxicity were calculated (Kaplan-Meier statistics). RESULTS: Median follow-up was
      five years. Overall, the incidence of late grade 3 and 2 rectal toxicity was 1%
      and 11%. The calculated three-year actuarial risk of developing late grade>=2
      rectal toxicity decreased from 16% to 7% and 5% for patients in Group 1, Group 2
      and Group 3, respectively (p<0.001). Respectively, 17 (4%) and 98 (24%) patients
      developed grade 3 and 2 late urinary toxicity in the primary setting. In the
      postoperative setting, 15 (6%) and 62 (26%) patients developed grade 3 and 2
      urinary toxicity, respectively. The three-year actuarial risk of developing
      late>=grade 2 urinary toxicity in primary- and postoperative-treated patients was
      22% and 23%, respectively. This was not significantly different between the three
      groups. CONCLUSION: The majority of patients developed no or only moderate rectal
      toxicity after high-dose IMRT for PC. Implementing different rectal DVC resulted
      in a significant decrease of late rectal toxicity without affecting urinary
      toxicity.

PMID- 25387269
TI  - Oligodendrocyte precursor cells modulate the neuronal network by activity
      dependent ectodomain cleavage of glial NG2.
AB  - The role of glia in modulating neuronal network activity is an important
      question. Oligodendrocyte precursor cells (OPC) characteristically express the
      transmembrane proteoglycan nerve-glia antigen 2 (NG2) and are unique glial cells
      receiving synaptic input from neurons. The development of NG2+ OPC into
      myelinating oligodendrocytes has been well studied, yet the retention of a large
      population of synapse-bearing OPC in the adult brain poses the question as to
      additional functional roles of OPC in the neuronal network. Here we report that
      activity-dependent processing of NG2 by OPC-expressed secretases functionally
      regulates the neuronal network. NG2 cleavage by the alpha-secretase ADAM10 yields
      an ectodomain present in the extracellular matrix and a C-terminal fragment that
      is subsequently further processed by the gamma-secretase to release an
      intracellular domain. ADAM10-dependent NG2 ectodomain cleavage and release
      (shedding) in acute brain slices or isolated OPC is increased by distinct
      activity-increasing stimuli. Lack of NG2 expression in OPC (NG2-knockout mice),
      or pharmacological inhibition of NG2 ectodomain shedding in wild-type OPC,
      results in a striking reduction of N-methyl-D-aspartate (NMDA) receptor-dependent
      long-term potentiation (LTP) in pyramidal neurons of the somatosensory cortex and
      alterations in the subunit composition of their alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepr opionicacid (AMPA) receptors. In NG2-knockout mice these neurons
      exhibit diminished AMPA and NMDA receptor-dependent current amplitudes;
      strikingly AMPA receptor currents can be rescued by application of conserved LNS
      protein domains of the NG2 ectodomain. Furthermore, NG2-knockout mice exhibit
      altered behavior in tests measuring sensorimotor function. These results
      demonstrate for the first time a bidirectional cross-talk between OPC and the
      surrounding neuronal network and demonstrate a novel physiological role for OPC
      in regulating information processing at neuronal synapses. 

PMID- 25387272
TI  - Progressive, Site-Specific Loss of Muscle Mass in Older, Frail Nursing Home
      Residents.
AB  - To clarify the progression of muscle loss in nursing home residents, frail women
      (n = 16; age: 85 +/- 9 years; residence time: 764 days) were assessed for
      physical activity, caloric intake, and site-specific muscle thickness (MTH) and
      subcutaneous fat thickness (SFT) using B-mode ultrasound at nine anatomical sites
      at four intervals over one year. Height, body weight, and BMI did not change.
      Physical activity (246 steps/ day) and nutritional intake (1,441 kcal, 60.3 g
      protein/day) were unaltered throughout the study. Subjects experienced a
      significant, progressive loss of muscle indicated by decrements in anterior upper
      arm (20%), posterior upper arm (25%), abdomen (20%), subscapular (33%), anterior
      thigh (15%), posterior thigh (22%), anterior lower leg (11%), posterior lower leg
      (13%), and forearm (15%) MTH. At study inception, prevalence of sarcopenia was
      related to muscle loss in the upper leg, while upper body muscle wasting
      contributed to sarcopenia later and was unrelated to physical activity,
      nutritional input, or duration of residence. 

PMID- 25387273
TI  - Latching chains in K-nearest-neighbor and modular small-world networks.
AB  - Latching dynamics retrieve pattern sequences successively by neural adaption and
      pattern correlation. We have previously proposed a modular latching chain model
      in Song et al. (2014) to better accommodate the structured transitions in the
      brain. Different cortical areas have different network structures. To explore how
      structural parameters like rewiring probability, threshold, noise and feedback
      connections affect the latching dynamics, two different connection schemes, K
      nearest-neighbor network and modular network both having modular structure are
      considered. Latching chains are measured using two proposed measures
      characterizing length of intra-modular latching chains and sequential inter
      modular association transitions. Our main findings include: (1) With decreasing
      threshold coefficient and rewiring probability, both the K-nearest-neighbor
      network and the modular network experience quantitatively similar phase change
      processes. (2) The modular network exhibits selectively enhanced latching in the
      small-world range of connectivity. (3) The K-nearest-neighbor network is more
      robust to changes in rewiring probability, while the modular network is more
      robust to the presence of noise pattern pairs and to changes in the strength of
      feedback connections. According to our findings, the relationships between
      latching chains in K-nearest-neighbor and modular networks and different forms of
      cognition and information processing emerging in the brain are discussed.

PMID- 25387274
TI  - Fluorescent carbonaceous nanodots for noninvasive glioma imaging after angiopep-2
      decoration.
AB  - Fluorescent carbonaceous nanodots (CDs) have attracted much attention due to
      their unique properties. However, their application in noninvasive imaging of
      diseased tissues was restricted by the short excitation/emission wavelengths and
      the low diseased tissue accumulation efficiency. In this study, CDs were prepared
      from glucose and glutamic acid with a particle size of 4 nm. Obvious emission
      could be observed at 600 to 700 nm when CDs were excited at around 500 nm. This
      property enabled CDs with capacity for deep tissue imaging with low background
      adsorption. Angiopep-2, a ligand which could target glioma cells, was anchored
      onto CDs after PEGylation. The product, An-PEG-CDs, could target C6 glioma cells
      with higher intensity than PEGylated CDs (PEG-CDs), and endosomes were involved
      in the uptake process. In vivo, An-PEG-CDs could accumulate in the glioma site at
      higher intensity, as the glioma/normal brain ratio for An-PEG-CDs was 1.73. The
      targeting effect of An-PEG-CDs was further demonstrated by receptor staining,
      which showed An-PEG-CDs colocalized well with the receptors expressed in glioma.
      In conclusion, An-PEG-CDs could be successfully used for noninvasive glioma
      imaging. 

PMID- 25387277
TI  - Polymer conformations in polymer nanocomposites containing spherical
      nanoparticles.
AB  - We investigate the effect of various spherical nanoparticles on chain dimensions
      in polymer melts for high nanoparticle loading which is larger than the
      percolation threshold, using molecular dynamics simulations. We show that polymer
      chains are unperturbed by the presence of repulsive nanoparticles. In contrast
      polymer chains can be perturbed by the presence of attractive nanoparticles when
      the polymer radius of gyration is larger than the nanoparticle radius. At high
      nanoparticle loading, chains can be stretched and flattened by the nanoparticles,
      even oligomers can expand under the presence of attractive nanoparticles of very
      small size. 

PMID- 25387275
TI  - The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond.
AB  - The selective transport of proteins or lipids by vesicular transport is a
      fundamental process supporting cellular physiology. The budding process involves
      cargo sorting and vesicle formation at the donor membrane and constitutes an
      important process in vesicular transport. This process is particularly important
      for the polarized sorting in epithelial cells, in which the cargo molecules need
      to be selectively sorted and transported to two distinct destinations, the apical
      or basolateral plasma membrane. Adaptor protein (AP)-1, a member of the AP
      complex family, which includes the ubiquitously expressed AP-1A and the
      epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network
      and/or at the recycling endosomes. A growing body of evidence, especially from
      studies using model organisms and animals, demonstrates that the AP-1-mediated
      polarized sorting supports the development and physiology of multi-cellular units
      as functional organs and tissues (e.g., cell fate determination, inflammation and
      gut immune homeostasis). Furthermore, a possible involvement of AP-1B in the
      pathogenesis of human diseases, such as Crohn's disease and cancer, is now
      becoming evident. These data highlight the significant contribution of AP-1
      complexes to the physiology of multicellular organisms, as master regulators of
      polarized sorting in epithelial cells. 

PMID- 25387276
TI  - Active and passive smoking and the incidence of asthma in the Black Women's
      Health Study.
AB  - RATIONALE: Evidence linking active or passive smoking to the incidence of adult
      onset asthma is inconsistent with both positive and inverse associations being
      reported. Most previous studies of active smoking have not accounted for passive
      smoke exposure, which may have introduced bias. OBJECTIVES: To assess the
      separate associations of active and passive smoking to the incidence of adult
      onset asthma in the U.S. Black Women's Health Study, a prospective cohort of
      African American women followed since 1995 with mailed biennial questionnaires.
      METHODS: Active smoking status was reported at baseline and updated on all follow
      up questionnaires. Passive smoke exposure during childhood, adolescence, and
      adulthood was ascertained in 1997. Asthma cases comprised women who reported
      doctor-diagnosed asthma with concurrent asthma medication use. Cox regression
      models were used to derive multivariable hazard ratios (HRs) and 95% confidence
      intervals (CIs) for former and current smoking and for passive smoking among
      nonsmokers compared with a reference category of never active or passive smokers.
      MEASUREMENTS AND MAIN RESULTS: Among 46,182 participants followed from 1995 to
      2011, 1,523 reported incident asthma. The multivariable HRs for former active
      smoking, current active smoking, and passive smoking only were, respectively,
      1.36 (95% CI, 1.11-1.67), 1.43 (95% CI, 1.15-1.77), and 1.21 (95% CI, 1.00-1.45),
      compared with never active/passive smoking. CONCLUSIONS: In this large population
      with 16 years of follow-up, active smoking increased the incidence of adult-onset
      asthma, and passive smoke exposure increased the risk among nonsmokers. Continued
      efforts to reduce exposure to tobacco smoke may have a beneficial effect on the
      incidence of adult-onset asthma.

PMID- 25387278
TI  - Encapsulation and stabilization of polyoxometalates in self-assembled
      supramolecular hydrogels.
AB  - We have encapsulated the polyoxoanions [P2W18O62](6-) and [P2W15V3O62](9-) in a
      self-assembled carboxy-methyl-chitosan (CMC) hydrogel, exhibiting a regular
      superstructure in water at physiological pH. We performed stability studies as a
      function of temperature and polyoxometalate (POM) loading, and observed
      exceptional Tgel properties. This work is a step forward towards developing
      biologically active polyoxometalate-based materials. 

PMID- 25387279
TI  - A field study of discrete emotions: athletes' cognitive appraisals during
      competition.
AB  - PURPOSE: Cognitive-motivational-relational theory (CMRT) emphasizes that
      cognitive appraisal components and core relational themes (in which the 6
      separate appraisal judgments are brought together as 1) are the proximal
      determinants of athletes' emotions. This study aimed to explore appraisals
      associated with discrete emotions experienced by athletes during competition by
      adopting a naturalistic, qualitative video-assisted approach. METHOD: Thirty self
      confrontation interviews were conducted with 11 national table-tennis players.
      Qualitative inductive and deductive content analyses were conducted on the
      participants' transcripts. RESULTS: Content analyses suggested that primary and
      secondary appraisal components (goal relevance, goal congruence, ego involvement,
      blame or credit, coping potential, and future expectations) were associated with
      a range of positive and negative discrete emotions: self-, other-, and
      environmental-oriented anger, anxiety, discouragement, disappointment, disgust,
      joy, serenity, relief, hope, and pride. Hierarchical content analyses also
      provided some support for the concept of core relational themes. CONCLUSION:
      Findings of the present study are consistent with a CMRT approach and highlight
      that primary and secondary appraisals as well as core relational themes are
      associated with discrete emotions experienced by athletes while competing.
      Limitations and practical applications of this study are discussed.

PMID- 25387280
TI  - Electron microscopy in rapid viral diagnosis: an update.
AB  - Diagnostic electron microscopy (DEM) has conceptual predecessors a?" the
      application of the sense of vision and of light microscopy in medicine. The
      evolvement of DEM and the role of its two branches - histopathology and rapid
      negative-contrast DEM - are described in this review, with a focus on the latter.
      By its resolving power of 2 nm in praxi, DEM is able to visualize all kinds of
      pathogens, bacteria, parasites, even the smallest viruses. In contrast to other
      laboratory diagnostic methods, DEM excels by speed and "open view". All
      structures on the support grid can be assigned directly by "pattern recognition"
      of their fine structure to a specific family of agents. The morphology-based
      "catch-all" diagnosis can be decisive as a differential diagnosis and will help
      as a preliminary diagnosis to select and apply proper diagnostic tools for typing
      of the observed agent. Based on two case reports, the advantages and possible
      pitfalls of DEM are exemplified and hints are given to make DEM reliable and
      effective. Finally the role of DEM in medicine and the wider fields of life
      sciences are described together with the organizational conditions to guarantee
      its future in laboratory diagnostics.

PMID- 25387281
TI  - Recommendations for the use of hepatitis C virus protease inhibitors for the
      treatment of chronic hepatitis C in HIV-infected persons. A position paper of the
      Italian Association for the Study of Infectious and Tropical Disease.
AB  - The efficacy data obtained with boceprevir and telaprevir for persons with
      hepatitis C virus (HCV) genotype 1 infection raise the question of whether HCV
      protease inhibitors should be used in human immunodeficiency virus (HIV)/HCV co
      infected persons. The Italian Association for the Study of Infectious and
      Tropical Diseases has made these recommendations to provide the rationale and
      practical indications for the use of triple anti-HCV therapy in persons living
      with HIV (PLWHIV). A Writing Committee of experts indicated by the President of
      the Association and a Consulting Committee con- tributed to the document. The
      final draft was submitted to the evaluation of external experts and the text
      modified according to their suggestions and comments. Treatment of HCV co
      infection should be considered for all HCV RNA positive PLWHIV. Response-guided
      therapy with pegylated interferon and ribavirin is the standard treatment of
      PLWHIV with infection by HCV genotype 2, 3, 4, 5 and 6. Boceprevir and telaprevir
      should be used to treat HCV genotype 1 infection in HIV/HCV co-infected patients
      for 48 weeks on an individual basis, with close monitoring of their efficacy and
      tolerability with concur- rent antiretroviral therapy, taking into account
      potential drug-drug interactions. The decision to treat a patient or to wait for
      better treatment options, or to discontinue treatment should be made on an
      individual basis taking into account pre-treatment variables and the on-treatment
      HCV RNA kinetics. 

PMID- 25387282
TI  - Monotherapy with lopinavir/ritonavir versus standard of care in HIV-infected
      patients virologically suppressed while on treatment with protease inhibitor
      based regimens: results from the MoLo study.
AB  - This study compared the cost-efficacy ratios of lopinavir/ritonavir monotherapy
      (LPV/r-MT) and of standard of care in virologically suppressed HIV-infected
      patients. The results of the efficacy and safety analyses are presented. We
      conducted a multicentre, randomised, open-label trial of HIV-infected adults on
      stable treatment, with HIV- RNA <50 copies/mL, randomised to continue the ongoing
      regimen (cART-arm) or to switch to LPV/r (400/100 mg BID) MT (MT-arm). Time to
      virological rebound (VR = confirmed HIV-RNA ?50 copies/mL) was estimated by Ka-
      plan-Meier method and changes in laboratory values during follow-up were
      evaluated by univariate mixed-linear models. Ninety-four patients were randomised
      and analysed (43 in the MT-arm and 51 in the cART-arm). Five (four in the MT and
      1 in the cART-arm; p=0.175) had VR, but time to VR did not statistically differ
      between the two arms (p=0.143). Major PI mutations were not detected at VR.
      Patients on MT had significant increases in total choles- terol [difference in
      mean change between MT and cART arm: 0.77 (+/-0.30) mg/dL per month; p=0.012] and
      eGFR [difference in mean change between MT and cART arm: 0.24 (+/-0.11)
      mL/min/1.73 m2 per month; p=0.029]. LPV/r-MT seems safe in most patients and
      should be considered in patients who have developed kidney toxicity from
      tenofovir. 

PMID- 25387283
TI  - Point-of-care testing for HCV infection: recent advances and implications for
      alternative screening.
AB  - Over the last few years, hepatitis C virus (HCV) infection has emerged as one of
      the most significant causes of chronic liver disease worldwide, with an estimated
      prevalence ranging from 2.2 to 3.0%. In Italy, approximately 2% of subjects are
      infected with HCV. Considering that acute HCV infection is usually asymptomatic,
      early diagnosis is rare. Those people who develop chronic infection, even though
      undiagnosed, may suffer serious liver damage, making chronic HCV infection a
      major health problem. New initiatives are needed to identify a submerged portion
      of patients with chronic viral hepatitis and to propose controls and antiviral
      treatments to avoid the progression to liver cirrhosis or hepatocellular
      carcinoma (HCC). Since January 2011, the Infectious Diseases Department of San
      Raffaele Scientific Institute in Milan has been carrying out a prevention program
      called "EASY test project", using a new oral test, the OraQuickA(r) HCV rapid
      antibody test (OraSure technologies, Inc.). The main objective of the project is
      to evaluate the acceptability of an alternative, free and anonymous HCV test
      offer, available in different settings (Points of Care, STDs Prevention clinics
      and General Practitioner clinics). From January 2011 to April 2014, 29,600
      subjects were approached to inform them about HCV infection and other sexually
      transmitted diseases; 4,507 (15.2% of the contacted subjects) of them, total
      eligible volunteers, performed HCV tests on saliva and completed the interview in
      the alternative POCTs. Twenty-seven subjects (0.6% of the total) turned HCV oral
      test reactive (27/4.507) during the evaluation period; all of them were confirmed
      by conventional test. All 27 patients were asymptomatic and without a history of
      HCV-re- lated symptoms. The results from this analysis suggest that the promotion
      of alternative HCV test screening has not yet been fully developed as a strategy
      to increase levels of HCV testing among people at risk for HCV infection.
      Increasing awareness of these alternative tests among individuals at risk and
      providers may be an appropriate strategy to increase the number of people who
      know their serological status. The recent introduction of rapid oral HCV antibody
      test could completely change the HCV diagnosis approach by facilitating the
      possibility of testing millions of people worldwide (in particular in the
      developing countries). 

PMID- 25387284
TI  - Occurrence of Prototheca spp. in cow milk samples.
AB  - Protothecosis is a potential zoonotic disease associated with bovine mastitis
      which can be transmitted to humans through contaminated milk. Considering the
      increasing prevalence of bovine mastitis due to Prototheca species, individual
      cow milk samples were analyzed using microbiological examination and biomolecular
      assay. Aspects related to health requirements for milk production, clinical and
      histological bovine mastitis were also described. The results showed 24/257
      (9.3%) culture-positive samples and 42/257 (16.3%) PCR-positive samples. Moreover
      in 5 cows with somatic cell count over 106/mL presented histological features of
      mastitis. This study reveals that the presence of Prototheca species in dairy
      herds was related to the hygienic conditions of the milking equipment, showing an
      emerging public health issue. 

PMID- 25387285
TI  - Detection of azole susceptibility patterns in clinical yeast strains isolated
      from 1998 to 2008.
AB  - 4,860 clinical yeast isolates (25 genera, 47 species) were tested in parallel to
      fluconazole, itraconazole, ketoconazole, and voriconazole. After re-evaluation of
      all species according to their current valid taxonomic denominations, the range
      of the top four of the dermatology, gynaecology and paediatrics associated
      species from superficial infections was similar to those isolated from other
      wards with mainly systemic/invasive infections. Candida albicans (44.7%) was the
      most frequent pathogen followed by C. glabrata, C. tropicalis, and C.
      parapsilosis. The MIC-assessment revealed for the ten-year test period an overall
      azole-susceptibility of about 75%, and ~80% for their associated ICUs. The
      overall susceptibility of the isolates from systemic and superficial infections
      to the four azoles was 79% and 80% respectively, and demonstrates a high in vitro
      activity. When two test periods (1998-2001 and 2002-2008) were compared by
      characteristic MIC values and multi-azole resistance, no significant increase
      could be detected in azole susceptibility/resistance over the two periods,
      respectively, over the total investigation period of ten years. This holds true
      when the characteristic MIC values were compared with those from different azole
      susceptibility studies from similar time periods and from different investigators
      around the world (1991 to 2010). With a new method, susceptibility pattern
      analysis for fungi, detailed information of multi-resistant microorganism
      populations could be obtained, and different characteristic resistance patterns
      in clinical yeast species detected. Although at a relatively low level, multi
      resistance was seen in individual species populations demonstrating resistance to
      two (6.7%), three (4.4%), or all four (4%) azoles tested. A level of 4% and 2%
      fourfold parallel resistance was also determined in Candia spp. and non-Candida
      spp. derived of blood culture isolates.

PMID- 25387286
TI  - Evaluation of BiesseBioscreen as a new methodology for bacteriuria screening.
AB  - Urinary tract infection is a common disease diagnosed from symptoms and clinical
      signs, and bacterial count per volume of urine. This study have evaluated the
      BiesseBioscreen analyzer as a new way to analyze urine samples en- abling fast
      screening of urine, prior to reference standard methods currently utilized in
      microbiology analysis labo- ratory. We analyzed 962 urine samples from
      outpatients and inpatients of the Tor Vergata (TV) University Hospital of the
      University of Rome "Tor Vergata". All samples were processed both with the
      BiesseBioscreen and with the standard methodology adopted by the clinical
      microbiology laboratory of TV Hospital and the results were com- pared. Of the
      samples analyzed 54.9% were concordant negative with the reference method and
      21.6% concordant positive, 23.3% resulted false positive and 0.2% false negative.
      The results obtained from BiesseBioscreen showed a sensitivity of 99.0%,
      indicating it as a system suitable to rule out urinary tract infection.
      BiesseBioscreen could represent a valid method for screening negative samples to
      exclude from culture test with a potential reduction in time, workload and costs
      of the diagnosis. 

PMID- 25387287
TI  - Are E-test and Vitek2 good choices for tigecycline susceptibility testing when
      comparing broth microdilution for MDR and XDR Acinetobacter baumannii?
AB  - This study reports the results of antimicrobial susceptibility testing of 10 MDR
      and 74 XDR Acinetobacter bauman- nii clinical isolates from our hospital routine.
      We used three different methods: two automated systems (Sensititre and VITEK 2)
      and one standardized manual method (E-test). Since many published papers refer to
      in vitro tests performed by E-test, the aim of this study was to test if this
      method is reliable for testing tigecycline. The results obtained show that E-test
      significantly overestimates the MIC of the broth microdilution (reference test),
      thus ob- taining a significant number of major errors (resistant instead of
      sensitive). VITEK 2 also shows the same problem, but it is less critical. We
      therefore conclude that these methods do not seem to be very reliable in the
      performance of susceptibility testing of MDR and XDR Acinetobacter baumannii
      against tigecycline. 

PMID- 25387288
TI  - Opposite effect of supernatants from selected periopathogens and oral
      lactobacilli cultures on ATP levels in human gingival fibroblasts.
AB  - Studies were performed on the effects of supernatants obtained from bacterial
      cultures, including cultures of Porphyromonas gingivalis, Aggregatibacter
      actinomycetemcomitans, Prevotella intermedia and Lactobacillus acidophilus
      strains on ATP levels in human gingival fibroblasts (HGF-1) and on their
      viability. ATP levels were evaluated using luminescence test and cell viability
      was estimated using a fluorescence test. In control cultures mean levels of ATP
      in HGF-1 amounted to 4.90+/-0.32 mln RLU. Supernatants of P. gingivalis and A.
      actinomycetemcomitans cultures were found to significantly reduce ATP production
      in HGF-1 (mean levels of ATP amounted to 3.41+/-0.33 and 3.55+/-0.3 mln RLU
      respectively), which was not accompanied by an increased proportion of dead
      fibroblasts. Supernatants of P. intermedia induced no significant alterations in
      ATP level in HGF-1. In turn, supernatants of L. acidophilus H2O2 (+) and H2O2 (-)
      cultures significantly increased ATP levels in HGF-1 (the mean levels amounted to
      5.94+/-0.31 mln RLU and 5.88+/-0.28 mln RLU respectively). The results indicate
      that extracellular products of P. gingivalis and A. actinomycetemcomitans most
      probably represent mitochondria-targeted peptides, which reduce synthesis of ATP
      in HGF-1. In turn, extracellular products of L. acidophilus seem to represent
      exopolysaccharides (EPS) with pro-oxidant activity, which stimulate synthesis of
      ATP in HGF-1. 

PMID- 25387289
TI  - Prevalence of six periodontal pathogens in subgingival samples of Italian
      patients with chronic periodontitis.
AB  - The aim of this study was to investigate the subgingival prevalence of six
      periodontal pathogens in 352 Italian patients with chronic periodontitis.
      Possible correlations with clinical parameters, age, gender and smoking status
      were also investigated. At first visit a pooled subgingival plaque sample was
      obtained for each subject by using the paper-point method. The samples were
      processed and analysed according to a commercially available quantitative real
      time polymerase chain reaction assay (Meridol(r) Perio Diagnostics, GABA
      International, Switzerland). Porphyromonas gingivalis (Pg), Treponema denticola
      (Td), Tannerella forsythia (Tf), Prevotella intermedia (Pi), Fusobacterium
      nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa) were investigated.
      Fn resulted the most frequently detected (95%) while Tf showed the highest load
      (12x105 cells/plaque sample). Aa was the less represented bacteria for load and
      presence. Bacterial load of Pg, Td, Tf and Fn showed a direct correlation to
      Bleeding On Probing (BOP) and presence of suppuration (p=0.0001). The bacterial
      load was always directly correlated to Probing Pocket Depth (PPD) (p=0.0001).
      Among the investigated variables, PPD resulted the most important risk indicator
      for periodontal pathogens. BOP appeared as a risk indicator for Td, Tf, Pg
      detection. Few studies have described the microbiological pattern of chronic
      periodontal disease in the Italian population. Considering the different forms of
      periodontitis, similar investigations in other countries are needed to disclose
      any microbiological differences among populations, which may lead to more
      specific approaches to prevention and therapy. 

PMID- 25387290
TI  - Phosphorylation-dependent interaction between a serine/threonine kinase PknA and
      a putative cell division protein Wag31 in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis genome contains eleven serine/threonine protein
      kinases (STPKs). Among these ST- PKs, PknA is a key component of signal
      transduction pathway that regulates cell shape and possibly cell division in M.
      tuberculosis via reversible phosphorylation of intracellular proteins. The in
      vitro peptide library screen showed that Wag31, a putative cell division protein,
      was a new substrate phosphorylated by PknA. The signal transduction pathway
      involving Wag31 and PknA plays a unique role in M. tuberculosis growth regulation
      that may participate in the pathogenesis of tuberculosis. In this study, genes of
      PknA, wild-type Wag31 (Wag31WT), phosphoablative Wag31T73A, and phosphomimetic
      Wag31T73E were cloned and expressed. Far-western analyses were performed using
      partial purified PknA and completely purified Wag31 proteins (Wag31WT, Wag31T73A,
      and Wag31T73E). Far-western analysis data revealed that the direct interaction
      between PknA and Wag31 is dependent on the phos- phorylation state of Wag31,
      which can represent a novel target for the development of new anti-tuberculosis
      drugs. 

PMID- 25387291
TI  - Antibacterial activity and cytotoxic effect of SIAB-GV3.
AB  - The aim of this study was to evaluate the antibacterial activity and cytotoxic
      effect of the compound SIAB-GV3, a new formulation presenting as an aqueous
      suspension of silicon dioxide (SiO2) functionalized with silver (Ag+)
      nanoparticles and benzalkonium. The product is formulated as an adjuvant for the
      treatment of inflammatory diseases of the oral cavity. This study demonstrates
      that SIAB-GV3 possesses strong antimicrobial activity against most of the common
      oral pathogens, in particular against Streptococcus pyogenes, Porphyromonas
      gingivalis and Aggregatibacter actinimycetemcomitans. The cytotoxic effect
      against human embryo lung fibroblasts (HELF cells) was evaluated at different
      times, from 1 h to 168 h, using concentrations of SIAB-GV3 ranging from 50 mg/ml
      to 0.0008 mg/ml. At the concentration of 10 mg/ml, commonly used in clinical
      practice, the compound results cyto- toxic after about 2 hours, this time being
      much longer than the typical time of local application, which is no more than 10
      minutes. In conclusion, our findings suggest that SIAB-GV3 has a good
      antibacterial activity against the most common oral pathogens even at very low
      concentrations and a low cytotoxic activity, thanks to the synergistic effects of
      Ag nanoparticles, silicon dioxide and benzalkonium. 

PMID- 25387292
TI  - No evidence of xenotropic murine leukemia virus-related virus infection in
      Brazilian multiply transfused patients with sickle cell disease and beta
      thalassemia major.
AB  - Although xenotropic murine leukemia virus-related virus (XMRV) has been regarded
      as a laboratory contaminant, it remains one of the most controversial viruses.
      The objective of the study was to determine if XMRV is present in 44 patients
      with beta-thalassemia major, 48 with sickle cell disease, and 89 volunteer blood
      donors. After RNA/ DNA extraction from plasma/buffy coat the samples were
      screened for XMRV sequences by conserved nested GAG primers. None of the RNA
      samples showed a positive result. Surprisingly, four DNA samples obtained from
      blood donors were positive for XMRV provirus. The subsequent phylogenetic
      analysis revealed that these sequences are identical to the positive control
      (murine leukemia retrovirus) and are probably consistent with laboratory
      contamination. XMRV infection (provirus and viral RNA) was absent in multiply
      transfused patients and volunteer blood donors. The positive result obtained from
      some blood donors probably reflects laboratory contamination. We believe that
      XMRV does not pose risk to blood transfusion.

PMID- 25387293
TI  - Prevalence and characterization of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae in food-producing animals in Northern Italy.
AB  - The aim of this study was to assess the production of extended spectrum beta
      lactamases (ESBL) in 56 strains of Enterobacteriaceae, obtained from 100 rectal
      swabs of farm animals, and to evaluate the horizontal transfer ca- pacity of the
      genetic determinants of resistance. The ESBL-positive strains were confirmed by
      phenotypic testing, confirmed by PCR and DNA sequence analysis. The localization
      of beta-lactamase genes was established by conju- gation experiments. Of the 56
      analyzed strains, 20 (36%) resulted positive for ESBL production by the double
      disk synergy test, and belonged to Escherichia coli 15 (75%) and Klebsiella
      ozaenae 5 (25%) species. Molecular analysis showed that all ESBL-producing
      isolates possessed genes encoding for TEM-type enzymes and/or CTX-M. The
      conjugation assays yielded positive results, thus denoting a plasmidic
      localization of the genes. This study high- lights the high percentage of ESBL
      positive Enterobacteriaceae and the mobility of the responsible genes. Gene mo-
      bility implies highly negative consequences in terms of drug therapy because of
      the spread of antibiotic resistance. 

PMID- 25387294
TI  - Multilocus sequence typing of Campylobacter jejuni and Campylobacter coli from
      humans and chickens in North-Eastern Italy.
AB  - This paper reports the multilocus sequence typing (MLST) of 57 C. jejuni and C.
      coli isolates from humans and chickens in Italy and the identification of 17 new
      sequence types (STs). A high genetic diversity was detected among C. jejuni/C.
      coli and human/chicken isolates, with a predominance of clonal complexes CC21 and
      CC828. Although human STs were not the same as those found in chickens, 3 CCs
      overlapped between human and chicken isolates. Genotyping of Campylobacter
      strains by MLST should be encouraged in order to implement surveillance and con-
      trol of infection in humans and in animal reservoirs in Italy. 

PMID- 25387295
TI  - In vitro activity of clinically implemented beta-lactams against Aerococcus
      urinae: presence of non-susceptible isolates in Switzerland.
AB  - We analyzed the in vitro susceptibility to several ?-lactams and vancomycin of 80
      Aerococcus urinae isolates collected during 2011-2012 in Switzerland. MICs were
      determined by Etest (bioMerieux) on Muller-Hinton agar with 5% sheep blood and
      interpreted according to the CLSI and EUCAST criteria set for viridans
      streptococci. MIC50/90 for penicillin, amoxicillin, ceftriaxone and vancomycin
      were 0.016/0.064 mg/l, 0.032/0.064 mg/l, 0.125/0.5 mg/l and 0.38/0.5 mg/l,
      respectively. Three (3.8%) isolates were resistant to ceftriaxone regardless of
      the criteria used (MICs ?2 mg/l); one of them was also non-susceptible to
      penicillin (MIC of 0.25 mg/l) according to CLSI. beta-lactam resistance in A.
      urinae is a concern and suggests that more studies are needed to determine the
      molecular mechanisms of such resistance.

PMID- 25387296
TI  - Identification of Inquilinus limosus in cystic fibrosis: a first report in Italy.
AB  - Cystic fibrosis is a genetic disorder associated with a polymicrobial lung
      infection where classical pathogens and newly identified bacteria may interact.
      Inquilinus limosus is an a-proteobacterium recently isolated in the airways of
      cystic fibrosis patient. We report the first case in Italy of I.limosus isolation
      from the sputum sample of a cystic fibrosis patient. The patient is a 20-years
      old man with cystic fibrosis, regularly attending the Regional Care Center for
      Cystic Fibrosis at the Federico II University Hospital of Naples. Microbiological
      culture methods detected a mu- coid gram negative bacillus in the patient's
      sputum sample. The isolate exhibited a distinct antimicrobial suscep- tibility
      profile with a high MIC for several drugs. The MALDI-TOF mass spectrometry
      analysis indicated the bac- terium isolated as I. limosus, confirmed by 16s rDNA
      sequence analysis. The described clinical case demonstrates how the bacterial
      biodiversity in the airways of cystic fibrosis patients is still underestimated.
      Cystic fibrosis lung represents an ecological niche suitable for growth of a wide
      variety of unusual bacteria not commonly associated with human diseases, such as
      I. limosus. Therefore further studies are needed to evaluate the epidemiology and
      clinical implications of I. limosus in the physiopathology of cystic fibrosis
      lung infection. 

PMID- 25387297
TI  - CONSORT item adherence in top ranked anaesthesiology journals in 2011: a
      retrospective analysis.
AB  - BACKGROUND: Randomised controlled trials (RCTs) are the gold standard for
      measuring the efficacy of any medical intervention. The present study assesses
      the implementation of the CONSORT statement in the top 11 anaesthesiology
      journals in 2011. OBJECTIVES: We designed this study in order to determine how
      well authors in the top 11 ranked anaesthesiology journals follow the CONSORT
      statement's criteria. DESIGN: A retrospective cross-sectional data analysis.
      SETTING: The study was performed at the RWTH Aachen University Hospital.
      PARTICIPANTS: Journals included Pain, Anesthesiology, British Journal of
      Anaesthesia, Regional Anesthesia and Pain Medicine, European Journal of Pain,
      Anesthesia and Analgesia, Anaesthesia, Minerva Anestesiologica, Canadian Journal
      of Anesthesia, Journal of Neurosurgical Anesthesiology and the European Journal
      of Anaesthesiology. MAIN OUTCOME MEASURES: All articles in the online table of
      contents from the top 11 anaesthesiology journals according to the ISI Web of
      Knowledge were screened for RCTs published in 2011. The RCTs were assessed using
      the CONSORT checklist. We also analysed the correlation between the number of
      citations and the adherence to CONSORT items. RESULTS: We evaluated 319 RCTs and
      found that, more than ten years after the publication of the CONSORT statement,
      the RCTs satisfied a median of 60.0% of the CONSORT criteria. Only 72.1% of the
      articles presented clearly defined primary and secondary outcome parameters. The
      number of citations is only weakly associated with the fulfilment of the CONSORT
      statement (r = 0.023). CONCLUSION: Adherence to the CONSORT criteria remains low
      in top-ranked anaesthesiology journals. We found only a very weak correlation
      between the number of citations and fulfilment of the requirements of the CONSORT
      statement.

PMID- 25387298
TI  - Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring
      cardiac output with transpulmonary thermodilution in patients with severe sepsis
      and septic shock: an observational study.
AB  - BACKGROUND: Cardiac output (CO) measurement is often required in critically ill
      patients. The performances of newer, less invasive techniques require evaluation
      in patients with severe sepsis and septic shock. OBJECTIVES: To compare
      calibrated arterial pressure waveform analysis-derived CO (COap,
      VolumeView/EV1000) and the uncalibrated form (COfv, FloTrac/Vigileo) with
      transpulmonary thermodilution derived CO (COtptd). DESIGN: A prospective,
      observational, single-centre study. SETTING: ICU of a general teaching hospital.
      PATIENTS: Twenty consecutive patients with severe sepsis or septic shock
      requiring haemodynamic monitoring by VolumeView/EV1000 and receiving mechanical
      ventilation. INTERVENTION: Connection of FloTrac/Vigileo to radial artery
      catheter already in situ. MAIN OUTCOME MEASURES: Radial (COfv) and femoral (COap)
      arterial waveform-derived CO measurements were compared with COtptd with respect
      to bias, precision, limits of agreement and percentage error, and the percentage
      error in the course of time since the last calibration of COap by COtptd.
      RESULTS: In comparing COap with COtptd (n = 267 paired measurements), the bias
      was 0.02 and limits of agreement were -2.49 to 2.52 l min, with a percentage
      error of 31%. The percentage error between COap and COtptd remained less than 30%
      until 8 h after calibration. In comparing COfv with COtptd (n = 301), the bias
      was -0.86 l min and limits of agreement were -4.48 to 2.77 l min, with a
      percentage error of 48%. The biases of COap and COfv correlated with systemic
      vascular resistance [r = 0.13 (P = 0.029) and r = 0.42 (P < 0.001),
      respectively]. Clinically significant changes in COap and COfv correlated
      positively with COtptd at r = 0.51 (P < 0.001) and r = 0.64 (P < 0.001),
      respectively. CONCLUSION: There was moderate agreement when measuring CO with
      either arterial waveform analysis technique. Compared with the uncalibrated COfv,
      the recently introduced calibrated arterial pressure waveform analysis-derived
      COap was more accurate and less dependent on vascular tone for up to 8 hours
      after callibation when monitoring CO in patients with severe sepsis and septic
      shock. The COap and COfv methods have poor to moderate CO-tracking abilities.

PMID- 25387299
TI  - Comparing charcoal and zeolite reflection filters for volatile anaesthetics: A
      laboratory evaluation.
AB  - BACKGROUND: A modified heat-moisture exchanger that incorporates a reflecting
      filter for use with partial rebreathing of exhaled volatile anaesthetics has been
      commercially available since the 1990 s. The main advantages of the device are
      efficient delivery of inhaled sedation to intensive care patients and reduced
      anaesthetic consumption during anaesthesia. However, elevated arterial CO2 values
      have been observed with an anaesthetic conserving device compared with a
      conventional heat and moisture exchanger, despite compensation for larger
      apparatus dead space. OBJECTIVE: The objective of this study is to thoroughly
      explore the properties of two reflecting materials (charcoal and zeolites).
      DESIGN: A controlled, prospective, observational laboratory study. SETTING: Lund
      University Hospital, Sweden, from December 2011 to December 2012. PARTICIPANTS:
      None. INTERVENTIONS: Three filters, with identical volumes, were compared using
      different volatile anaesthetics at different conditions of temperature and
      moisture. The filtering materials were charcoal or zeolite. Glass spheres were
      used as an inert control. MAIN OUTCOME MEASURES: Consumption of volatile
      anaesthetics using different reflecting materials in filters at different
      conditions regarding temperature and moisture. CO2 reflection by the filtering
      materials: glass spheres, charcoal or zeolite. RESULTS: Isoflurane consumption in
      an open system was 60.8 g h(-1). The isoflurane consumption in dry, warm air was
      39.8 g h(-1) with glass spheres. Changing to charcoal and zeolite had a profound
      effect on isoflurane consumption, 11.8 and 10.7 g h(-1), respectively. Heating
      and humidifying the air as well as the addition of N2O created only minor changes
      in consumption. The percentage of isoflurane conserved by the charcoal filter was
      independent of the isoflurane concentration (0.5 to 4.5%). Reflection of
      sevoflurane, desflurane and halothane by the charcoal filter was similar to
      reflection of isoflurane. Both charcoal and zeolite filters had CO2 reflecting
      properties and end-tidal CO2 increased by 3 to 3.7% compared with glass spheres.
      This increase was attenuated to 1 to 1.4% when the air was heated and humidified,
      and isoflurane was added. CONCLUSION: Charcoal and zeolite possess gas-reflecting
      properties, which can be used to conserve volatile anaesthetics. They also
      reflect CO2. The degree of CO2 reflection was reduced by heating and humidifying
      the air.

PMID- 25387300
TI  - Development of a specific algorithm to guide haemostatic therapy in children
      undergoing cardiac surgery: a single-centre retrospective study.
AB  - BACKGROUND: Although rotational thromboelastometry (ROTEM) is increasingly used
      to guide haemostatic therapy in a bleeding patient, there is a paucity of data
      guiding its use in the paediatric population. OBJECTIVE: The objective of this
      study is to develop an algorithm on the basis of ROTEM values obtained in our
      paediatric cardiac population to guide the management of the bleeding child.
      DESIGN: A retrospective analysis. SETTING: Department of Anaesthesiology, Queen
      Fabiola Children's University Hospital. Data were collected between September
      2010 and January 2012. PATIENTS: All children who underwent elective cardiac
      surgery requiring cardiopulmonary bypass (CPB) were reviewed. INTERVENTION: None.
      MAIN OUTCOME MEASURES: Significant postoperative bleeding was defined as blood
      loss more than 10% of the child's estimated blood volume within the first six
      postoperative hours, dividing our population according to high blood loss (HBL)
      or low blood loss (LBL). Factors independently associated with postoperative
      bleeding determined the bleeding probability. Receiving operating characteristics
      (ROC) curves were constructed with the aim of determining relevant ROTEM
      parameters (including clot amplitude 10 min after administration of protamine
      [A10]) to be used in our algorithm. The sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) were determined for
      the developed algorithm. RESULTS: One-hundred and fifty children were included in
      our study. Univariate and multivariate logistic regression analysis revealed that
      preoperative weight (kg), presence of a cyanotic disease (yes/no) and wound
      closure duration (min) were independent predictors of postoperative bleeding.
      Analysis of our ROTEM parameters revealed that clotting time (CT) >= 111 s, A10
      <= 38 mm measured on the EXTEM and A10 <= 3 mm obtained on the FIBTEM tests were
      the three relevant parameters to guide haemostatic therapy. If the ROTEM-based
      algorithm was applied according to the bleeding risk (n = 65), 27 out of 29 of
      the HBL and 24 out of 36 of the LBL group would have been treated. CONCLUSION:
      This study describes an algorithm starting with the detection of abnormal
      bleeding in which ROTEM could be used to guide haemostatic therapy in bleeding
      children after CPB. Further studies are needed to test the efficacy of this
      specific algorithm-based approach.

PMID- 25387301
TI  - Comparison of McGrath and Pentax-AWS Airwayscope for tracheal intubation by
      anaesthesiologists during chest compression in a manikin: A randomised crossover
      trial.

PMID- 25387302
TI  - Pudendal block in transurethral prostatectomy: A randomised trial.

PMID- 25387303
TI  - Presepsin in the prognosis of infectious diseases and diagnosis of infectious
      disseminated intravascular coagulation: a prospective, multicentre, observational
      study.
AB  - BACKGROUND: Few prospective studies have described the prognostic accuracy of
      presepsin for 28-day mortality during days 0 to 7, or its role in the diagnosis
      of disseminated intravascular coagulation (DIC) in patients with infection.
      OBJECTIVE: We aimed to evaluate the clinical usefulness of presepsin levels by
      comparing infection markers such as procalcitonin, interleukin-6 and C-reactive
      protein, as well as markers of DIC such as fibrin degradation products (FDPs) and
      D-dimer, from days 0 to 7. DESIGN: A prospective, multicentre, observational
      study. SETTING: Four medical institutions between June 2010 and June 2011.
      PATIENTS: A total of 191 patients who fulfilled at least one of the systemic
      inflammatory response syndrome (SIRS) criteria were enrolled in the study. MAIN
      OUTCOME MEASURES: The presepsin levels were evaluated for their diagnostic
      accuracy in discriminating between SIRS and sepsis, the prognostic accuracy for
      28-day mortality from days 0 to 7 and the diagnostic accuracy for DIC in patients
      with infection by comparison with other infection markers. RESULTS: The
      diagnostic accuracy for discriminating between SIRS and sepsis from combining the
      presepsin and procalcitonin measurements [area under the curve (AUC), 0.91;
      likelihood ratio, 4.96] was higher than that of presepsin (AUC, 0.89; likelihood
      ratio, 4.75) or procalcitonin (AUC, 0.85; likelihood ratio, 3.18) alone. Not only
      the correlation coefficient between the presepsin level and the sequential organ
      failure assessment (SOFA) score but also the prognostic accuracy of presepsin for
      28-day mortality increased with the elapsed time, and both were highest at day 7.
      The diagnostic accuracy for DIC generated by combining presepsin and FDP (AUC,
      0.84; likelihood ratio, 3.57) was higher than that of FDP (AUC, 0.82; likelihood
      ratio, 2.64) or presepsin (AUC, 0.80; likelihood ratio, 2.94) alone. CONCLUSION:
      The prognosis and severity of infection may be assessed more accurately by
      measuring the presepsin levels until day 7. Presepsin is a useful diagnostic tool
      for DIC with infection.

PMID- 25387304
TI  - A survey of acute pain services in Portuguese hospitals: are we on the right
      track?

PMID- 25387305
TI  - Reply to: Intravenous bolus injection of dexamethasone and transient excruciating
      perineal pain.

PMID- 25387306
TI  - Editorial comment for del junco et Al.

PMID- 25387307
TI  - Lower denticity leading to higher stability: structural and solution studies of
      Ln(III)-OBETA complexes.
AB  - The heptadentate ligand OBETA (2,2'-oxybis(ethylamine)-N,N,N',N'-tetraacetic
      acid) was reported to form complexes with Ln(3+) ions more stable than those
      formed by the octadentate and more popular congener EGTA (ethylene glycol O,O'
      bis(ethylamine)-N,N,N',N'-tetraacetic acid). The structural features leading to
      this puzzling coordination paradox were investigated by X-ray diffraction,
      solution state NMR, molecular modeling, and relaxometric studies. The stability
      constant of Gd(OBETA) (log KGdL = 19.37, 0.1 M KCl) is 2 orders of magnitude
      higher than that of the higher denticity analogue Gd(EGTA) (log KGdL = 17.66, 0.1
      M KCl). The half-lives (t1/2) for the dissociation reactions of Gd(OBETA) and
      Gd(EGTA) ([Cu(2+)]tot = 0.2 mM, [Cit(3-)]tot = 0.5 mM, [PO4(3-)]tot = 1.0 mM, and
      [CO3(2-)]tot = 25 mM at pH = 7.4 and 25  degrees C in 0.1 M KCl solution) are 6.8
      and 0.63 h, respectively, reflecting the much higher inertness of Gd(OBETA) near
      physiological conditions. NMR studies and DFT calculations using the B3LYP
      functional and a large-core ECP indicate that the [Gd(OBETA)(H2O)2](-) complex
      most likely exists in solution as the
      Delta(lambdalambda)(deltadeltadeltadelta)A/Lambda(deltadelta)(lambdalambdalambdal
      mbda)A enantiomeric pair, with an activation free energy for the
      enantiomerization process of ~40 kJ.mol(-1). The metal ion is nine-coordinate by
      seven donor atoms of the ligand and two inner-sphere water molecules. The X-ray
      crystal structure of [C(NH2)3]3[Lu(OBETA)(CO3)].2H2O is in agreement with the
      predictions of DFT calculations, the two coordinated water molecules being
      replaced by a bidentate carbonate anion. The (1)H NMRD and (17)O NMR study
      revealed that the two inner-sphere water molecules in Gd(OBETA) are endowed with
      a relatively fast water exchange rate (kex(298) = 13 * 10(6) s(-1)). The higher
      thermodynamic stability and inertness of Ln(OBETA) complexes, peaking in the
      center of the 4f series, combined with the presence of two coordinated water
      molecules suggests that Gd(OBETA) is a promising paramagnetic probe for MRI
      applications. 

PMID- 25387308
TI  - Implication of pattern-recognition receptors in cardiovascular diseases.
AB  - SIGNIFICANCE: Pattern-recognition receptors (PRRs) are a family of receptors that
      are used to detect pathogen-associated molecular patterns or damage-associated
      molecular patterns, which initiate immune responses to resolve infections and
      repair damaged tissues. Abnormalities in PRR activation will unavoidably lead to
      excessive inflammation. RECENT ADVANCES: Although multiple pathophysiological
      processes are involved in cardiovascular disease, recent studies have highlighted
      the importance of innate PRRs, in particular, Toll-like receptors and nucleotide
      binding oligomerization domain-like receptors, in mediating inflammatory
      responses and cardiovascular function. CRITICAL ISSUES: The functional roles and
      regulatory mechanisms of PRRs in cardiovascular diseases are still largely
      unknown. In particular, controversies exist on the certainty of these detrimental
      or beneficial effects of some PRRs in different diseased states or different
      experimental animal models. FUTURE DIRECTIONS: Considering that the molecular
      mechanisms for individual PRR to regulate cellular function are complex and
      multiple PRRs are activated simultaneously or synergistically, a better
      understanding of the function of individual PRRs and the interplay of PRRs will
      provide unexpected opportunities to develop new therapies for cardiovascular
      disease by modulation of an innate immune system.

PMID- 25387309
TI  - Extending medium-range predictability of extreme hydrological events in Europe.
AB  - Widespread flooding occurred across northwest Europe during the winter of
      2013/14, resulting in large socioeconomic damages. In the historical record,
      extreme hydrological events have been connected with intense water vapour
      transport. Here we show that water vapour transport has higher medium-range
      predictability compared with precipitation in the winter 2013/14 forecasts from
      the European Centre for Medium-Range Weather Forecasts. Applying the concept of
      potential predictability, the transport is found to extend the forecast horizon
      by 3 days in some European regions. Our results suggest that the breakdown in
      precipitation predictability is due to uncertainty in the horizontal mass
      convergence location, an essential mechanism for precipitation generation.
      Furthermore, the predictability increases with larger spatial averages. Given the
      strong association between precipitation and water vapour transport, especially
      for extreme events, we conclude that the higher transport predictability could be
      used as a model diagnostic to increase preparedness for extreme hydrological
      events. 

PMID- 25387311
TI  - A novel multiplex rt-PCR assay for the detection of four chromosomal
      translocations of leukemia.
AB  - AIMS: The object of the present study was to develop a novel multiplex reverse
      transcription-polymerase chain reaction (RT-PCR)-based assay to detect four
      common recurrent chromosomal translocations t(9;22)(q34;q11), t(15;17)(q22;q12),
      t(8;21)(q22;q22), and t(1;19)(q23;q13). RESULTS: This novel multiplex RT-PCR
      method can specifically detect these six positive plasmids with known
      transcripts, and the sensitivities were up to 10 copies. In the diagnosis of
      clinical specimens, four chromosomal translocations, including seven transcripts,
      were actually specifically detected. CONCLUSIONS: This newly developed multiplex
      RT-PCR system can be used to detect these four recurrent chromosomal
      translocations specifically and sensitively. It is novel, accurate, and time and
      cost effective in the detection of leukemia-specific chromosomal translocations.
      Assays with this new strategy will have a potential in detecting other
      chromosomal translocations in leukemias.

PMID- 25387312
TI  - Dolutegravir efficacy at 48 weeks in key subgroups of treatment-naive HIV
      infected individuals in three randomized trials.
AB  - OBJECTIVES: Dolutegravir (DTG) has been studied in three trials in HIV treatment
      naive participants, showing noninferiority compared with raltegravir (RAL), and
      superiority compared with efavirenz and ritonavir-boosted darunavir. We explored
      factors that predicted treatment success, the consistency of observed treatment
      differences across subgroups and the impact of NRTI backbone on treatment
      outcome. DESIGN: Retrospective exploratory analyses of data from three large,
      randomized, international comparative trials: SPRING-2, SINGLE, and FLAMINGO.
      METHODS: We examined the efficacy of DTG in HIV-infected participants with
      respect to relevant demographic and HIV-1-related baseline characteristics using
      the primary efficacy endpoint from the studies (FDA snapshot) and secondary
      endpoints that examine specific elements of treatment response. Regression models
      were used to analyze pooled data from all three studies. RESULTS: Snapshot
      response was affected by age, hepatitis co-infection, HIV risk factor, baseline
      CD4+ cell count, and HIV-1 RNA and by third agent. Differences between DTG and
      other third agents were generally consistent across these subgroups. There was no
      evidence of a difference in snapshot response between abacavir/lamivudine
      (ABC/3TC) and tenofovir/emtricitabine (TDF/FTC) overall [ABC/3TC 86%, TDF/FTC
      85%, difference 1.1%, confidence interval (CI) -1.8, 4.0 percentage points, P =
      0.61] or at high viral loads (difference -2.5, 95% CI -8.9, 3.8 percentage
      points, P = 0.42). CONCLUSIONS: DTG is a once-daily, unboosted integrase
      inhibitor that is effective in combination with either ABC/3TC or TDF/FTC for
      first-line antiretroviral therapy in HIV-positive individuals with a variety of
      baseline characteristics.

PMID- 25387313
TI  - Combination antiretroviral therapy reduces the detection risk of cervical human
      papilloma virus infection in women living with HIV.
AB  - OBJECTIVE: Data on the effect of combination antiretroviral therapy (cART) on
      cervical human papilloma virus (HPV) infection are both limited and conflicting.
      We aimed to determine the effect of the initiation of cART for HPV genotype
      detection on cervical samples in HIV-infected South African women. DESIGN:
      Prospective cohort study. METHODS: Generalized estimating equation was performed
      to estimate parameters of mixed-effects logistic regression models of cART on HPV
      cervical detection risk, adjusting for time-dependent covariates CD4 T-cell
      count, sexual activity and excision treatment. Ratio of odds ratios (ORs) was
      computed to compare the pooled cART effect on lower vs. high-risk HPV genotype
      groups, to the effect of cART on the risk of HPV-16 detection. RESULTS: Of the
      300 patients, 204 (68%) were commenced on ART during follow-up, as they met the
      criteria for cART initiation. cART significantly reduced the risk for detection
      of HPV by 77% [OR 0.23, 95% confidence interval (CI) 0.15-0.37]. cART
      significantly reduced the risk of HPV-16 detection (OR 0.50, 95% CI 0.37-0.67).
      Every month on cART significantly reduced the detection risk of any HPV type by
      9% (OR 0.91, 95% CI 0.89-0.94). The protective effect of cART on the detection
      risk for the low-risk HPV genotype group was significantly less than the
      protective effect of cART on the detection risk of HPV-16 (ratio of ORs 1.35, 95%
      CI 1.22-1.50). CONCLUSION: cART significantly reduced cervical HPV infection.
      This effect was dependent on the duration of exposure to cART and is the
      mechanism by which cART may improve the outcome of dysplasia in HIV-infected
      women.

PMID- 25387314
TI  - Therapy with boceprevir or telaprevir in HIV/hepatitis C virus co-infected
      patients to treat recurrence of hepatitis C virus infection after liver
      transplantation.
AB  - OBJECTIVE: Severe hepatitis C virus (HCV) recurrence affects post-transplant
      survival in HIV/HCV co-infected patients. This article describes the results of
      triple anti-HCV therapy with boceprevir or telaprevir in seven HIV/HCV co
      infected patients following liver transplantation. METHODS: All patients had
      severe HCV recurrence [fibrosis stage >=F2 or acute hepatitis >=A2 (n = 5) or
      fibrosing cholestatic hepatitis (n = 2)] associated with genotype 1a (n = 4) or
      1b (n = 3). Patients were treated with Peg-interferon/ribavirin and boceprevir (n
      = 2) or telaprevir (n = 5) immediately (n = 3) or after a 4-week lead-in phase (n
      = 4). Immunosuppression included either cyclosporine (n = 5) or tacrolimus (n =
      2). Prior to introducing telaprevir, combined antiretroviral therapy was switched
      in one patient to prevent drug-drug interactions. RESULTS: At 24 weeks after the
      end of treatment, sustained virological response was observed in 60% (3/5) of the
      patients treated with telaprevir; no responders were observed in the boceprevir
      group. Triple anti-HCV therapy was prematurely discontinued in six patients
      [treatment failure (n = 2), infection (n = 2), acute rejection (n = 1) and
      myocardial infarction (n = 1)]. Anaemia occurred in all patients, requiring
      erythropoietin, ribavirin dose reduction and red blood cell transfusions in five
      patients.Average cyclosporine doses were reduced by 50-84% after telaprevir
      initiation and by 33% after boceprevir initiation. Tacrolimus doses were reduced
      by 95% with telaprevir. CONCLUSION: Our data suggest that in HIV/HCV co-infected
      patients, triple anti-HCV therapy with telaprevir greatly improved efficacy
      despite poor tolerability. Significant decreases in cyclosporine or tacrolimus
      doses are necessary prior to introduction of boceprevir or telaprevir. Close
      monitoring is essential to prevent drug-drug interactions among antiretroviral
      therapy, immunosuppressive agents and anti-HCV therapy.

PMID- 25387315
TI  - The contrasting cultures of HIV and tuberculosis care.

PMID- 25387316
TI  - Broad and persistent Gag-specific CD8+ T-cell responses are associated with viral
      control but rarely drive viral escape during primary HIV-1 infection.
AB  - OBJECTIVE: We characterized protein-specific CD8 T-cell immunodominance patterns
      during the first year of HIV-1 infection, and their impact on viral evolution and
      immune control. METHODS: We analyzed CD8 T-cell responses to the full HIV-1
      proteome during the first year of infection in 18 antiretroviral-naive
      individuals with acute HIV-1 subtype C infection, all identified prior to
      seroconversion. Ex-vivo and cultured interferon-gamma ELISPOT assays were
      performed and viruses from plasma were sequenced within defined CTL Gag epitopes.
      RESULTS: Nef-specific CD8 T-cell responses were dominant during the first 4 weeks
      after infection and made up 40% of the total responses at this time; yet, by 1
      year, responses against this region had declined and Gag responses made up to 47%
      of all T-cell responses measured. An inverse correlation between the breadth of
      Gag-specific responses and viral load set point was evident at 26 weeks after
      infection (P = 0.0081, r = -0.60) and beyond. An inverse correlation between the
      number of persistent responses targeting Gag and viral set point was also
      identified (P = 0.01, r = -0.58). Gag-specific responses detectable by the
      cultured ELISPOT assay correlated negatively with viral load set point (P =
      0.0013, r = -0.91). Sequence evolution in targeted and nontargeted Gag epitopes
      in this cohort was infrequent. CONCLUSIONS: These data underscore the importance
      of HIV-specific CD8 T-cell responses, particularly to the Gag protein, in the
      maintenance of low viral load levels during primary infection, and show that
      these responses are initially poorly elicited by natural infection. These data
      have implications for vaccine design strategies.

PMID- 25387317
TI  - Gut epithelial barrier and systemic inflammation during chronic HIV infection.
AB  - OBJECTIVE: Microbial translocation and innate immune action characterize HIV
      infection. Continued gut mucosal dysfunction during treatment and its
      relationship to CD4 T-cell recovery has not been well described. DESIGN: A cross
      sectional study was performed of antiretroviral therapy (ART)-suppressed
      (immunologic responders with CD4 > 500 cells/MUl and immunologic nonresponders
      with CD4 < 350 cells/MUl), untreated HIV-infected, and seronegative participants
      consenting to gut biopsies and a blood draw. METHODS: Neutrophil infiltration as
      a surrogate response to epithelial breach, colorectal epithelial proliferation as
      a measure of repair, and mucosal apoptosis by immunohistochemistry were
      determined in gut biopsies. Plasma markers of monocyte activation (sCD14), immune
      activation (interleukin-6), and indoleamine 2,3-dioxygenase-1 activity (plasma
      kynurenine/tryptophanratio) were concurrently measured. RESULTS: Each HIV
      infected group had greater neutrophil infiltration than controls. Similarly,
      untreated HIV-infected participants and ART-suppressed immunologic responders had
      increased epithelial proliferation compared with controls, but immunologic
      nonresponders had no appreciable increase in epithelial proliferation despite
      elevated neutrophil infiltration. The CD4 T-cell count was positively correlated
      with epithelial proliferation and was modestly negatively correlated with
      neutrophil infiltration in ART-suppressed patients. Epithelial proliferation was
      inversely correlated with mucosal apoptosis, and apoptosis was linked to plasma
      sCD14 and modestly to kynurenine/tryptophan ratio. CONCLUSIONS: Neutrophil
      infiltration and mucosal apoptosis remain abnormally high despite ART. Epithelial
      proliferation increases in HIV, but may be impaired in immunologic nonresponders.
      Whether mucosal apoptosis is a cause or consequence of epithelial proliferative
      defects is unclear, but appears to be associated with systemic inflammation. The
      impact of ART and interventions targeting the gut epithelial barrier in treated
      HIV infection warrant further investigation.

PMID- 25387318
TI  - Testosterone replacement therapy among HIV-infected men in the CFAR Network of
      Integrated Clinical Systems.
AB  - OBJECTIVE: The objectives of this study were to determine the rate of
      testosterone replacement therapy (TRT) initiation, TRT predictors and associated
      monitoring in HIV-infected men. DESIGN: A multisite cohort study. METHODS: We
      examined TRT initiation rates and monitoring among adult HIV-infected men in
      routine care at seven sites in the Centers for AIDS Research (CFAR) Network of
      Integrated Clinical Systems (CNICS) from 1996 to 2011. We determined TRT
      predictors using Cox regression modelling. RESULTS: Of 14 454 men meeting
      inclusion criteria, TRT was initiated in 1482 (10%) with an initiation rate of
      19.7/1000 person-years [95% confidence interval (95% CI) 18.7-20.7]. In the
      multivariable model, TRT was significantly associated with age at least 35 years,
      white race, diagnosis of AIDS wasting, hepatitis C coinfection, protease
      inhibitor based antiretroviral therapy and nadir CD4 cell count of 200 cells/MUl
      or less. Overall, 1886 out of 14 454 (13%) had testosterone deficiency. Among
      those initiating TRT, 992 out of 1482 (67%) had a pre-TRT serum total
      testosterone measured, and deficiency [<300 ng/dl (10.4 nmol/l)] was found in 360
      out of 1482 (24%). Post-TRT serum total testosterone was measured within 6 months
      of TRT initiation in 377 out of 1482 (25%) men. CONCLUSION: TRT was common in HIV
      infected men, though evidence for pre-TRT testosterone deficiency was lacking in
      76%. Endocrine guidelines for post-TRT monitoring were uncommonly followed. Given
      cardiovascular and other risks associated with TRT, efforts should focus on
      understanding factors driving these TRT practices in HIV-infected men.

PMID- 25387321
TI  - Obesity and cardiovascular disease.
AB  - Cardiovascular disease is the most common cause of mortality in rich countries
      and today it has the same meaning for health care as the epidemics of past
      centuries had for medicine in earlier times: 50% of the population in these
      countries die of cardiovascular disease. The amount of cardiovascular disease is
      also increasing in the developing countries together with economic growth. By
      2015 one in three deaths will globally be due to cardiovascular diseases.
      Coronary heart disease is a chronic disease that starts in childhood, even if the
      symptoms first occur in the middle age. The risks for coronary heart disease are
      well-known: lipid disorders, especially high serum LDL-cholesterol concentration,
      high blood pressure, tobacco smoking, obesity, diabetes, male gender and physical
      inactivity. Obesity is both an independent risk factor for cardiovascular disease
      but is also closely connected with several other risk factors. This review
      focuses on the connection between overweight or obesity and cardiovascular
      disease. 

PMID- 25387319
TI  - Factors associated with swallowing assessment after oral endotracheal intubation
      and mechanical ventilation for acute lung injury.
AB  - RATIONALE: Endotracheal intubation is associated with postextubation swallowing
      dysfunction, but no guidelines exist for postextubation swallowing assessments.
      OBJECTIVES: We evaluated the prevalence, patient demographic and clinical
      factors, and intensive care unit (ICU) and hospital organizational factors
      associated with swallowing assessment after oral endotracheal intubation and
      mechanical ventilation in patients with acute lung injury (ALI). METHODS: We
      performed a secondary analysis of a prospective cohort study in which
      investigators evaluated 178 eligible patients with ALI who were mechanically
      ventilated via oral endotracheal tube. The patients were recruited from 13 ICUs
      at four teaching hospitals in Baltimore, Maryland. Patient demographic and
      clinical factors, types of ICU, and hospital study sites were evaluated for their
      association with completion of a swallowing assessment both in the ICU and after
      the ICU stay before hospital discharge. Factors significantly associated with a
      swallow assessment were evaluated in a multivariable logistic regression model.
      MEASUREMENTS AND MAIN RESULTS: Before hospital discharge, 79 (44%) patients
      completed a swallowing assessment, among whom 59 (75%) had their assessments
      initiated in ICU and 20 (25%) had their assessments initiated on the hospital
      ward. Female sex (odds ratio [OR] = 2.01; 95% confidence interval [95% CI] = 1.03
      3.97), orotracheal intubation duration (OR = 1.13 per day; 95% CI = 1.05-1.22),
      and hospital study site (Site 3: OR = 2.41; 95% CI = 1.00-5.78) were
      independently associated with swallowing assessment. Although Site 3 had a
      twofold increase in swallowing assessments in the ICU, there was no significant
      difference between hospitals in the frequency of swallowing assessments completed
      after ICU discharge (P = 0.287) or in the proportion of patients who failed a
      swallowing assessment conducted in the ICU (P = 0.468) or on the ward (P =
      0.746). CONCLUSIONS: In this multisite prospective study, female sex, intubation
      duration, and hospital site were associated with postextubation swallowing
      assessment. These results demonstrate variability in practice patterns between
      institutions and highlight the need to determine the appropriate timing and
      indications for swallowing assessment and to more fully understand swallowing
      dysfunction after intubation.

PMID- 25387322
TI  - Influence of trainee participation on operative times for adult and pediatric
      cochlear implantation.
AB  - Objective Few studies have examined operative times for cochlear implantation
      (CI) using multivariable linear regression analyses to identify predictors of
      case length. Herein, we assess whether trainee participation, among other
      factors, influences operating room (OR) times. Methods We retrospectively
      reviewed total OR and procedural times for isolated unilateral implants over a 5
      year period (2009-2013) in children and adults. Total operating and procedural
      times were compared. Multivariable linear regression analyses were used to
      identify predictors of procedural time. Results We identified a total of 455
      unilateral CI procedures (n = 35 pediatric, n = 420 adult). Mean total OR time
      was 193.6 minutes (SD = 58.9 minutes) and mean procedural time was 147.1 minutes
      (SD = 56.2). The presence of trainees was associated with a significant
      difference in procedure time: 149.9 minutes (SD = 54.9) with trainees versus
      136.6 minutes (SD = 59.9) without trainees, P = 0.0375. Trainee involvement did
      not significantly increase total OR time: 196.3 minutes (SD = 56.9) with trainees
      versus 183.8 minutes (SD = 65.0) without trainees, P = 0.0653. Surgeon identity
      was also associated with differences in procedural time (P < 0.001). Patient age,
      gender, American Society of Anesthesiologists classification, and pediatric
      designation had no significant impact on length of case. Conclusions Major
      predictors of longer procedural OR times for CI are surgeon identity and trainee
      participation. Few published data exist on length of CI in an academic setting
      using multivariable linear regression analyses. Our data may be instructive for
      comparative analyses and have implications for operative planning and surgical
      education.

PMID- 25387323
TI  - Massive asymptomatic creatine kinase elevation in youth during antipsychotic drug
      treatment: case reports and critical review of the literature.
AB  - A massive asymptomatic creatine kinase elevation (MACKE) has been described
      during antipsychotic exposure in adult psychotic patients without signs of
      neuroleptic malignant syndrome (NMS), or other most frequent reasons for high
      creatine kinase (CK) serum level (intramuscular injections, restraints, intense
      physical activity, dystonic reactions). In this article, we review this clinical
      condition, and report three cases of MACKE in nonpsychotic, drug-naive youth
      during treatment with second generation antipsychotics. The diagnosis of MACKE
      should be considered after ruling out other possible common reasons of CK
      increase. The finding of MACKE should indicate a need for weekly monitoring of
      the CK level only when there are reasons to believe elevated CK is toxic or
      harmful. Further investigations are recommended when signs and symptoms raise a
      suspicion of NMS or rhabdomyolysis, including flu-like syndrome, fever, weakness,
      alteration of consciousness, muscle rigidity, tachycardia, hyper-/hypotension,
      and dark urine. A drug discontinuation should be considered when possible signs
      of NMS or rhabdomyolysis are suspected, or in cases of very high and persisting
      CK levels. Empirical evidence indicates that there is not a "safe" antipsychotic
      medication; therefore, a switch to another antipsychotic with a different profile
      is not necessarily a safe option. The spontaneously remitting or intermittent
      course suggests that the "true" MACKE should be kept distinct from both
      rhabdomyolysis and NMS. Raising awareness with MACKE may reduce the need for
      unnecessary diagnosis of NMS or rhabdomyolysis, which may otherwise lead to an
      unnecessary discontinuation of an effective therapeutic agent.

PMID- 25387324
TI  - Effects of active and passive recovery on blood lactate and blood pH after a
      repeated sprint protocol in children and adults.
AB  - The aim of this study was to compare the effect of active (AR) and passive
      recovery (PR) after a high-intensive repeated sprint running protocol on
      physiological parameters in children and adults. Blood lactate (La) and blood pH
      were obtained during two sets of 5 * 5 s all-out sprints and several times during
      subsequent 30-min recovery in 16 children and 16 adults. End-exercise La was
      significantly lower and pH significantly higher in children (La: 5.21 +/- 2.73
      mmol.L-1; pH: 7.37 +/- 0.06) compared with adults (La: 10.35 +/- 5.76 mmol.L-1;
      pH: 7.27 +/- 0.10) (p < .01). La half-life during postexercise recovery was
      significantly shorter in children (AR: 436 +/- 371 s, PR: 830 +/- 349 s) than in
      adults (AR: 733 +/- 371 s, PR: 1361 +/- 372 s), as well as in active compared
      with passive recovery for both age groups (p < .01). The age x recovery
      interaction for La half-life only approached statistical significance (p = .06).
      The results suggest a faster lactate disappearance and an earlier return to
      resting pH after a repeated sprint running protocol in children compared with
      adults and a less pronounced advantage of active recovery in children. 

PMID- 25387325
TI  - Completely laparoscopic ALPPS using round-the-liver ligation to replace
      parenchymal transection for a patient with multiple right liver cancers
      complicated with liver cirrhosis.
AB  - The "ALPPS" (associating liver partition with portal vein ligation for staged
      hepatectomy) procedure enables the rapid growth of the future liver remnant and
      extended surgical indication to patients with an "insufficient" future liver
      remnant. In May 2014, a 64-year-old male patient was admitted. The computed
      tomography (CT) scan showed multiple right liver lesions, which were diagnosed to
      be hepatocellular carcinoma by liver biopsy. The future liver remnant volume
      after right hemihepatectomy was calculated to be 35.6% based on the CT
      reconstruction. Completely laparoscopic ALPPS using round-the-liver ligation,
      which replaced liver splitting, was performed on him. The two-stage operation was
      performed successfully. The future liver remnant volume increased 37.9% according
      to the CT scan on Day 10 after the first-stage operation. The second-stage
      operation was performed on Day 14 after the first-stage operation. The patient
      recovered uneventfully. No bile leakage occurred. Thus the round-the-liver
      ligation can be safely executed in laparoscopy. Completely laparoscopic ALPPS
      using round-the-liver ligation is feasible and could result in a rapid
      hypertrophy of the liver remnant in patients with liver cancer complicated with
      cirrhosis.

PMID- 25387326
TI  - Bioavailability and kinetics of the antihypertensive casein-derived peptide HLPLP
      in rats.
AB  - The aim of this study was to investigate the oral bioavailability and kinetics of
      the milk casein-derived peptide HLPLP, which had previously demonstrated
      antihypertensive effect in spontaneously hypertensive rats. HLPLP disposition
      after single intravenous (4 mg/kg body weight) and oral (40 mg/kg body weight)
      doses was studied in rats. Plasma concentrations of HLPLP [beta-casein fragment
      f(134-138)], and two derived fragments found after HLPLP administration, LPLP
      [beta-casein fragment f(135-138)] and HLPL [beta-casein fragment f(134-137)],
      were determined by ultrahigh performance liquid chromatography (UPLC) coupled on
      line to a Q-TOF instrument. For HLPLP, the elimination half-lives (T1/2beta) were
      7.95 min after intravenous and 11.7 min after oral administration. The volume of
      distribution at steady state (Vss = 30.8 L/kg) suggests a considerable uptake of
      HLPLP into tissues. HLPLP was converted to the peptides LPLP and HLPL. After
      HLPLP intravenous administration, the elimination half-lives (T1/2beta) for these
      biotransformed peptides, LPLP and HLPL, were 8.38 and 10.9 min, respectively.
      After oral administration, HLPLP was rapidly absorbed with an absorption half
      life (T1/2a) of 2.79 min. The oral bioavailability of HLPLP was found to be
      5.18%. Our study suggested that HLPLP was rapidly absorbed and eliminated after
      oral administration, biotransformed into smaller fragments LPLP and HLPL, and
      distributed throughout the body by the circulation blood. The present
      pharmacokinetic information from a preclinical kinetic study in rats can also
      play an important role in designing future kinetic studies in humans for
      assessing HLPLP dose-response relationship. 

PMID- 25387327
TI  - Polarization versus temperature in pyridinium ionic liquids.
AB  - Electronic polarization and charge transfer effects play a crucial role in
      thermodynamic, structural, and transport properties of room-temperature ionic
      liquids (RTILs). These nonadditive interactions constitute a useful tool for
      tuning physical chemical behavior of RTILs. Polarization and charge transfer
      generally decay as temperature increases, although their presence should be
      expected over an entire condensed state temperature range. For the first time, we
      use three popular pyridinium-based RTILs to investigate temperature dependence of
      electronic polarization in RTILs, based on a nonperiodic electronic density
      description for a cation-anion pair. Atom-centered density matrix propagation
      molecular dynamics, supplemented by a weak coupling to an external bath, is used
      to simulate the temperature impact on system properties. We show that, quite
      surprisingly, nonadditivity in the cation-anion interactions changes negligibly
      between 300 and 900 K, while the average dipole moment increases due to thermal
      fluctuations of geometries. Our results contribute to the fundamental
      understanding of electronic effects in the condensed phase of ionic systems and
      foster progress in physical chemistry and engineering. 

PMID- 25387328
TI  - Highly efficient and recyclable nanocomplexed photocatalysts of AgBr/N-doped and
      amine-functionalized reduced graphene oxide.
AB  - Although silver bromide has recently drawn considerable attention because of its
      high photocatalytic activity, it tends to form agglomerated metallic silver under
      the irradiation of visible light. Therefore, photocatalytic activity decreases
      with time and cannot be applied for repeated uses. To overcome this limitation,
      in the present work, we complexed AgBr with nitrogen doped (N-doped) and amine
      functionalized reduced graphene oxide (GN). N-doped and/or amine functionalized
      graphene shows intrinsically good catalytic activity. Besides, amine groups can
      undergo complexation with silver ions to suppress its reduction to metallic Ag.
      As a result, these complexed catalysts show excellent photocatalytic activity for
      the degradation of methylene blue (MB) dye under the irradiation of visible
      light. Photocatalytic degradation of MB shows that the catalytic activity is
      optimized at a condition of 0.5 wt % GN, under which ~99% of MB was degraded only
      after 50 min of visible light irradiation. Notably, the complexed catalyst is
      quite stable and retained almost all of its catalytic activity even after greater
      than 10 repeated cycles. Moreover, the catalyst can also efficiently decompose 2
      chlorophenol, a colorless organic contaminant, under visible light exposure.
      Detailed experimental investigation reveals that hydroxyl (.OH) radicals play an
      important role for dye degradation reactions. A relevant mechanism for dye
      degradation has also been proposed.

PMID- 25387329
TI  - Insight into the photodissociation dynamical feature of conventional transition
      state and roaming pathways by an impulsive model.
AB  - Without the need to construct complicated potential energy surfaces, a
      multicenter impulsive model is developed to characterize the dynamical feature of
      conventional transition state (TS) and roaming pathways in the photodissociation
      of formaldehyde, H2CO -> CO + H2. The photofragment energy distributions (PED)
      resulting from the roaming mechanism are found to closely correlate to a
      particular configuration that lies close to the edge of the plateau-like
      intrinsic reaction coordinate, whereas such a PED is associated with the
      configuration at the saddle point when the conventional TS pathway is followed.
      The evaluated PED results are consistent with those by experimental findings and
      quasi-classical trajectory calculations. Following impulsive analysis, the
      roaming pathway can be viewed as a consequence of energy transfer events between
      several vibrational modes. For H2CO, the available energy initially accumulated
      at the C-H bond is transferred to other transitional mode(s) via stretching
      bending coupling, and finally to the HH stretching. 

PMID- 25387330
TI  - Short communication: Plasmacytoid dendritic cells from HIV-1 Elite Controllers
      maintain a gut-homing phenotype associated with immune activation.
AB  - Lentivirus infections are characterized by a dramatic loss of mucosal CD4(+) T
      cells, breakdown of the gut mucosa, and subsequent chronic immune activation.
      Residual immune activation persists even in patients controlling virus
      replication and remains a significant source of ongoing disease morbidities, but
      the causes are unclear. Plasmacytoid dendritic cells (pDCs), primary producers of
      interferon (IFN)-alpha, have been previously shown to be depleted from peripheral
      blood of HIV patients and simian immunodeficiency virus (SIV)-infected macaques,
      and most recently have been shown to accumulate in the gut mucosa. Although
      previous work has shown that pDC frequencies can be reduced in the circulation of
      HIV-1 Elite Controllers, it is unknown if gut-homing also occurs. In this new
      study we found that during progressive HIV-1 infection pDCs were depleted in
      peripheral blood compared to seronegative controls, and, correlating with plasma
      viremia, the remaining pDCs upregulated the gut-homing marker, alpha4beta7. Even
      in HIV-1 Elite Controllers pDCs were significantly reduced in blood and
      alpha4beta7 expression was still significantly upregulated compared to
      seronegative controls. Interestingly, pDC trafficking to the gut was associated
      with increased Ki67 and HLA-DR on circulating CD4(+) and CD8(+) T cells. Overall,
      these data suggest that gut trafficking of pDCs is independent of virus
      replication and could be mediated by alternative mechanisms, which in turn could
      contribute to residual immune activation in HIV-1 Elite Controllers.

PMID- 25387331
TI  - Binding of the PET radiotracer [18F]BF227 does not reflect the presence of alpha
      synuclein aggregates in transgenic mice.
AB  - Alpha-synuclein (alpha-syn) aggregation is a neuropathological hallmark of many
      neurodegenerative diseases, collectively termed synucleinopathies. There is
      currently no pre-mortem diagnosis tool for these diseases. Although some
      compounds have been described as potential ligands for alpha-syn aggregates, no
      specific PET radiotracer of aggregated alpha-syn is currently available.
      Recently, [(18)F]BF227 has been proposed as an alpha-syn PET radiotracer in the
      absence of other specific candidates. We proposed here, for the first time, to
      use this radiotracer in an accelerated mouse model of synucleinopathy presenting
      alpha-syn depositions in brainstem and thalamus. Our in vivo and in vitro studies
      showed that [(18)F]BF227 does not bind to alpha-syn aggregates. These results
      highlight the fact that [(18)F]BF227 PET has no suitable characteristics for
      monitoring this experimental synucleinopathy, justifying the need to develop
      alternative alpha-syn PET radiotracers. 

PMID- 25387332
TI  - Racial Differences in Gray Matter Integrity by Diffusion Tensor in Black and
      White Octogenarians.
AB  - OBJECTIVE: To quantify racial differences in brain structural characteristics in
      white and black octogenarians, and to examine whether these characteristics
      contribute to cognition. METHODS: Cross-sectional study of 283 adults 79-89 years
      old (59.4% white;42.0% women) with data on gray matter integrity via diffusion
      tensor imaging (mean diffusivity), gray matter atrophy (GMA), white matter
      hyperintensities (WMH), literacy, smoking, drinking, income, hypertension and
      diabetes. Participants were recruited from an ongoing epidemiological study of
      older adults living in the community with a range of chronic conditions, physical
      and cognitive function. Standardized betas (sbeta) of neuroimaging markers
      predicting Digit Symbol Substitution Test (DSST) and Modified Mini-Mental State
      Examination (3MS) scores were computed in multivariable regression models
      stratified by race. RESULTS: Compared to whites, blacks had lower DSST (p=0.001)
      and lower 3MS (p=0.006), but also lower mean diffusivity (i.e. higher gray matter
      microstructural integrity, p=0.032), independent of gender, income, literacy,
      body mass index, diabetes and drinking habits. Racial differences were not
      significant for WMH (p=0.062) or GMA (p=0.4). Among blacks, mean diffusivity and
      WMH were associated with DSST (sbeta=-.209, p=0.037 and -.211, p=.038,
      respectively) independent of each other and other covariates; among whites, mean
      diffusivity, but not WMH, was significantly associated with DSST and 3MS (sbeta =
      .277, p=.002 and -.250, p=0.029, respectively). CONCLUSIONS: In this cohort of
      octogenarians living in the community, blacks appeared to have higher
      microstructural integrity of gray matter as compared to whites. This neuroimaging
      marker was related to higher cognition even in the presence of WMH and other
      cardiovascular conditions. If confirmed, these findings suggest microstructural
      gray matter integrity may be a target to improve cognition, especially among
      blacks who survive to very old age with a range of chronic cardiovascular
      conditions.

PMID- 25387333
TI  - Amyloid precursor protein knockout diminishes synaptic vesicle proteins at the
      presynaptic active zone in mouse brain.
AB  - The amyloid precursor protein (APP) has previously been allocated to an
      organellar pool residing in the Golgi apparatus and in endosomal compartments,
      and in its mature form to a presynaptic active zone-localized pool. By analyzing
      homozygous APP knockout mice we evaluated the impact of APP on synaptic vesicle
      protein abundance at synaptic release sites. Following immunopurification of
      synaptic vesicles and the attached presynaptic plasma membrane, individual
      proteins were subjected to quantitative Western blot analysis. We demonstrate
      that APP deletion in knockout animals reduces the abundance of the synaptic
      vesicle proteins synaptophysin, synaptotagmin-1, and SV2A at the presynaptic
      active zone. Conversely, deletion of the additional APP family members, APLP1 and
      APLP2 resulted in an increase in synaptophysin, synaptogamin-1, and SV2A
      abundance. When transmembrane APP is lacking in APPsalpha-KI/APLP2-KO mice
      synaptic vesicle protein abundance corresponds to that in APP -KO mice. Deletion
      of the synaptic vesicle protein 2 (SV2) A and B had no effect on APP and
      synaptophysin abundance but decreased synaptotagmin-1. Our data suggest that APP
      controls the abundance of synaptic vesicle proteins at the presynaptic release
      sites and thus impacts synaptic transmission. 

PMID- 25387334
TI  - Clinical, genetic, and neuroimaging features of Early Onset Alzheimer Disease:
      the challenges of diagnosis and treatment.
AB  - Early Onset Alzheimer Disease (EOAD) is a rare condition, frequently associated
      with genetic causes. The dissemination of genetic testing along with biomarker
      determinations have prompted a wider recognition of EOAD in experienced clinical
      settings. However, despite the great efforts in establishing the contribution of
      causative genes to EOAD, atypical disease presentation and clinical features
      still makes its diagnosis and treatment a challenge for the clinicians. This
      review aims to provide an extensive evaluation of literature data on EOAD, in
      order to improve understanding and knowledge of EOAD, underscore its significant
      impact on patients and their caregivers and influence public policies. This would
      be crucial to define the urgency of evidence-based treatment approaches. 

PMID- 25387335
TI  - Caspase-3 short hairpin RNAs: a potential therapeutic agent in neurodegeneration
      of aluminum-exposed animal model.
AB  - There is abundant evidence supporting the role of caspases in the development of
      neurodegenerative disease, including Alzheimer's disease (AD). Therefore,
      regulating the activity of caspases has been considered as a therapeutic target.
      However, all the efforts on AD therapy using pan-caspase inhibitors have failed
      because of uncontrolled adverse effects. Alternatively, the specific knockdown of
      caspase-3 gene through RNA interference (RNAi) could serve as a future potential
      therapeutic strategy. The aim of the present study is to down-regulate the
      expression of caspase-3 gene using lentiviral vector-mediated caspase-3 short
      hairpin RNA (LV-Caspase-3 shRNA). The effect of LV-Caspase-3 shRNA on apoptosis
      induced by aluminum (Al) was investigated in primary cultured cortical neurons
      and validated in C57BL/6J mice. The results indicated an increase in apoptosis
      and caspase-3 expression in primary cultured neurons and the cortex ofmice
      exposed to Al, which could be down-regulated by LV-Caspase-3 shRNA. Furthermore,
      LV-Caspase-3 shRNA reduced neural cell death and improved learning and memory in
      C57BL/6J mice treated with Al. Our results suggest that LV-caspase-3 shRNA is a
      potential therapeutic agent to prevent neurodegeneration and cognitive
      dysfunction in aluminum- exposed animal models. The findings provide a rational
      gene therapy strategy for AD. 

PMID- 25387337
TI  - Locus (coeruleus) minoris resistentiae in pathogenesis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) represents the most prevalent form of dementia in the
      elderly. However, the pathological mechanisms underlying the development and
      progression of AD are only partially understood. To date, the accumulated
      clinical and experimental evidence indicate that the locus coeruleus (LC), the
      main source of brain's norepinephrine, represents "the epicenter" of pathology
      leading to the development of AD. Evidence for this includes observations that
      neurons of the LC modulate several processes that are altered in brains of AD
      patients, including synaptic plasticity, neuroinflammation, neuronal metabolism,
      and blood-brain-barrier permeability. Moreover, the LC undergoes significant
      degeneration in the brains of AD patients and is considered a source of the prion
      like spreading of tau pathology to forebrain structures innervated by the
      noradrenergic neurons of the LC. Furthermore, lesions of the LC exaggerate AD
      related pathology, while augmentation of the brain's noradrenergic
      neurotransmission reduces both neuroinflammation and cognitive decline. We
      hypothesize that better understanding the role of the LC neurons in AD
      pathogenesis may lead to development of new strategies for the treatment of AD. 

PMID- 25387338
TI  - Functional connectivity in a rat model of Alzheimer's disease during a working
      memory task.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by
      progressive loss of memory. Impairment of working memory was typically observed
      in AD. The concept of brain functional connectivity plays an important role in
      neuroscience as a useful tool to understand the organized behavior of brain.
      Hence, the purpose of this study is to investigate the possible mechanism of
      working memory deficits in AD from a new perspective of functional connectivity.
      Rats were randomly divided into 2 groups: Abeta injection group (Abeta1-42
      induced toxicity rat model) and control group. Multi-channel local field
      potentials (LFPs) were obtained from rat prefrontal cortex with implanted
      microelectrode arrays while the rats performed a Y-maze working memory task. The
      short-time Fourier transform was utilized to analyze the power changes in LFPs
      and sub-bands (in particular theta and low gamma bands) were extracted via band
      filtering. Then the Directed transfer function (DTF) method was applied to
      calculate the functional connections among LFPs. From the DTF calculation, the
      causal networks in the sub-bands were identified. DTFmean (mean of connectivity
      matrix elements) was used to quantify connection strength as well as global
      efficiency (Eglob) was calculated to quantitatively describe the efficient of
      information transfer in the network. Our results showed that both connection
      strength and efficient of information transfer increased during the working
      memory task in the control group; by contrast, there was no significantly change
      in the Abeta injection group. These findings could lead to improve the
      understanding of the mechanism of working memory deficits in AD.

PMID- 25387336
TI  - Structure and mechanism of action of tau aggregation inhibitors.
AB  - Since the discovery of phenothiazines as tau protein aggregation inhibitors, many
      additional small molecule inhibitors of diverse chemotype have been discovered
      and characterized in biological model systems. Although direct inhibition of tau
      aggregation has shown promise as a potential treatment strategy for depressing
      neurofibrillary lesion formation in Alzheimer's disease, the mechanism of action
      of these compounds has been unclear. However, recent studies have found that tau
      aggregation antagonists exert their effects through both covalent and non
      covalent means, and have identified associated potency and selectivity driving
      features. Here we review small-molecule tau aggregation inhibitors with a focus
      on compound structure and inhibitory mechanism. The elucidation of inhibitory
      mechanism has implications for maximizing on-target efficacy while minimizing off
      target side effects. 

PMID- 25387339
TI  - Effect of trichostatin A on gelsolin levels, proteolysis of amyloid precursor
      protein, and amyloid beta-protein load in the brain of transgenic mouse model of
      Alzheimer's disease.
AB  - In vivo and in vitro studies have shown that gelsolin is an anti-amyloidogenic
      protein. Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes
      the expression of gelsolin. Fibrillized amyoid beta-protein (Abeta) is a key
      constituent of amyloid plaques in the brains of patients with Alzheimer's disease
      (AD). We studied the effects of TSA on the levels of gelsolin; amyloid precursor
      protein (APP); proteolytic enzymes (gamma-secretase and beta-secretase)
      responsible for the production of Abeta; Abeta-cleaving enzymes, i.e., neprilysin
      (NEP) and insulin-degrading enzyme (IDE); and amyloid load in the double
      transgenic (Tg) APPswe/PS1(deltaE9) mouse model of AD. Intraperitoneal injection
      of TSA for two months (9-11 months of age) resulted in decreased activity of
      HDAC, and increased levels of gelsolin in the hippocampus and cortex of the brain
      in AD Tg mice as compared to vehicle-treated mice. TSA also increased the levels
      of gamma-secretase and beta-secretase activity in the brain. However, TSA did not
      show any effect on the activities or the expression levels of NEP and IDE in the
      brain. Furthermore, TSA treatment of AD Tg mice showed no change in the amyloid
      load (percent of examined area occupied by amyloid plaques) in the hippocampus
      and cortex, suggesting that TSA treatment did not result in the reduction of
      amyloid load. Interestingly, TSA prevented the formation of new amyloid deposits
      but increased the size of existing plaques. TSA treatment did not cause any
      apoptosis in the brain. These results suggest that TSA increases gelsolin
      expression in the brain, but the pleiotropic effects of TSA negate the anti
      amyloidogenic effect of gelsolin in AD Tg mice.

PMID- 25387340
TI  - Brain perfusion SPECT with Brodmann areas analysis in differentiating
      frontotemporal dementia subtypes.
AB  - Despite the known validity of clinical diagnostic criteria, significant overlap
      of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in
      several cases, resulting in great uncertainty of the diagnostic boundaries. We
      evaluated the perfusion between FTD subtypes using brain perfusion (99m)Tc-HMPAO
      SPECT with Brodmann areas (BA) mapping. NeuroGam software was applied on single
      photon emission computed tomographic (SPECT) studies for the semi-quantitative
      evaluation of perfusion in BA and the comparison with the software's normal
      database. We studied 91 consecutive FTD patients: 21 with behavioural variants
      (bvFTD), 39 with language variants (lvFTD) [12 with progressive non-fluent
      aphasia (PNFA), 27 with semantic dementia (SD)], and 31 patients with progressive
      supranuclear palsy (PSP)/corticobasal degeneration (CBD). Stepwise logistic
      regression analyses showed that the BA 28L and 32R could independently
      differentiate bvFTD from lvFTD, while the BA 8R and 25R could discriminate bvFTD
      from SD and PNFA, respectively. Additionally, BA 7R and 32R were found to
      discriminate bvFTD from CBD/PSP. The only BA that could differentiate SD from
      PNFA was 6L. BA 6R and 20L were found to independently differentiate CBD/PSP from
      lvFTD. Moreover, BA 20L and 22R could discriminate CBD/PSP from PNFA, while BA
      6R, 20L and 45R were found to independently discriminate CBD/PSP from SD. Brain
      perfusion SPECT with BA mapping can be a useful additional tool in
      differentiating FTD variants by improving the definition of brain areas that are
      specifically implicated, resulting in a more accurate differential diagnosis in
      atypical or uncertain forms of FTD.

PMID- 25387341
TI  - Islet amyloid polypeptide (IAPP): a second amyloid in Alzheimer's disease.
AB  - Amyloid formation is the pathological hallmark of type 2 diabetes (T2D) and
      Alzheimer's disease (AD). These diseases are marked by extracellular amyloid
      deposits of islet amyloid polypeptide (IAPP) in the pancreas and amyloid beta
      (Abeta) in the brain. Since IAPP may enter the brain and disparate amyloids can
      cross-seed each other to augment amyloid formation, we hypothesized that
      pancreatic derived IAPP may enter the brain to augment misfolding of Abeta in AD.
      The corollaries for validity of this hypothesis are that IAPP [1] enters the
      brain, [2] augments Abeta misfolding, [3] associates with Abeta plaques, and most
      importantly [4] plasma levels correlate with AD diagnosis. We demonstrate the
      first 3 corollaries that: (1) IAPP is present in the brain in human cerebrospinal
      fluid (CSF), (2) synthetic IAPP promoted oligomerization of Abeta in vitro, and
      (3) endogenous IAPP localized to Abeta oligomers and plaques. For the 4th
      corollary, we did not observe correlation of peripheral IAPP levels with AD
      pathology in either an African American cohort or AD transgenic mice. In the
      African American cohort, with increased risk for both T2D and AD, peripheral IAPP
      levels were not significantly different in samples with no disease, T2D, AD, or
      both T2D and AD. In the Tg2576 AD mouse model, IAPP plasma levels were not
      significantly elevated at an age where the mice exhibit the glucose intolerance
      of pre-diabetes. Based on this negative data, it appears unlikely that peripheral
      IAPP cross-seeds or "infects" Abeta pathology in AD brain. However, we provide
      novel and additional data which demonstrate that IAPP protein is present in
      astrocytes in murine brain and secreted from primary cultured astrocytes. This
      preliminary report suggests a potential and novel association between brain
      derived IAPP and AD, however whether astrocytic derived IAPP cross-seeds Abeta in
      the brain requires further research. 

PMID- 25387342
TI  - Effect of Goniosynechialysis During Phacoemulsification on IOP in Patients With
      Medically Well-controlled Chronic Angle-Closure Glaucoma.
AB  - PURPOSE: To evaluate and compare the efficacy and safety of combined
      phacoemulsification and goniosynechialysis (PEGS) to phacoemulsification alone
      (PE) in patients with medically well-controlled chronic angle-closure glaucoma
      (CACG) with cataracts. MATERIALS: Thirty eyes diagnosed with CACG and requiring
      cataract surgery from January 2008 to October 2010 were prospectively randomized,
      15 each to PE and PEGS. Changes in peripheral anterior synechiae (PAS),
      intraocular pressure (IOP), anterior chamber depth, and number of antiglaucoma
      drugs from baseline to 2 months after the operation were analyzed, as were the
      type and number of complications. RESULTS: The PE group showed decreases in PAS
      (118.67+/-95.38 degrees) and IOP (2.33+/-2.38 mm Hg) and a significant reduction
      in the number of antiglaucoma drugs (0.53+/-0.83, P<0.05) from before to 2 months
      after surgery. The PEGS group showed similar decreases in PAS (114.00+/-90.95
      degrees), and IOP (4.53+/-4.16 mm Hg) and number of antiglaucoma drugs (1.20+/
      1.32) (P<0.05). However, the amount of decline in both the groups did not show
      any significantly difference in PAS, reduction of IOP, or number of antiglaucoma
      drugs (P>0.05), The increase in anterior chamber depth from baseline to 2 months
      after surgery was significantly greater in the PEGS group (P=0.003). CONCLUSIONS:
      The IOP-lowering effects of PEGS do not differ significantly from those of PE in
      medically well-controlled CACG patients with cataract. These results suggest that
      additional goniosynechialysis during phacoemulsification is not necessary in such
      patients.

PMID- 25387344
TI  - Pregnancy-induced hypertension is associated with an increase in the prevalence
      of cardiovascular disease risk factors in Japanese women.
AB  - OBJECTIVE: This study assessed whether pregnancy-induced hypertension (PIH)
      affects the prevalence of cardiovascular disease (CVD) risk factors in later life
      among Japanese women. METHODS: Study participants were 1,185 women (mean [SD]
      age, 46.5 [5.6] y; range, 38-73 y) aged 40 years or older who underwent a health
      checkup at a periodic health examination facility between January 2012 and
      December 2013 and had experienced giving birth. Questionnaires were sent to
      potential participants, and they were encouraged to provide their Maternal and
      Child Health Handbook (handbook). We recruited 101 women with a history of PIH
      (PIH group) and 1,084 women with uncomplicated pregnancy at delivery (control
      group). Groupings were based on information from the handbook. We assessed the
      association between PIH and CVD in later life among Japanese women by focusing on
      hypertension, diabetes mellitus, and dyslipidemia as risk factors for CVD. Odds
      ratios (ORs) for the use of antihypertensive, diabetes mellitus, and dyslipidemic
      medications in the PIH group were determined. RESULTS: Women with PIH had
      increased risk of antihypertensive medication use compared with women without PIH
      (2.9% vs 13.9%; OR, 4.28; 95% CI, 2.14-8.57). Triglycerides were significantly
      higher and high-density lipoprotein cholesterol was significantly lower in the
      PIH group than in the control group. The OR for dyslipidemic medication use in
      the PIH group relative to the control group was 3.20 (95% CI, 1.42-7.22).
      CONCLUSIONS: Our findings suggest that a history of PIH may be associated with an
      increased risk of hypertension (a risk factor for CVD) in later life among
      Japanese women.

PMID- 25387343
TI  - Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl
      isothiocyanate and curcumin.
AB  - The role of phytochemicals in preventive and therapeutic medicine is a major area
      of scientific research. Several studies have illustrated the mechanistic roles of
      phytochemicals in Nrf2 transcriptional activation. The present study aims to
      examine the importance of the transcription factor Nrf2 by treating peritoneal
      macrophages from Nrf2(+/+) and Nrf2(-/-) mice ex vivo with phenethyl
      isothiocyanate (PEITC) and curcumin (CUR). The peritoneal macrophages were
      pretreated with the drugs and challenged with lipopolysaccharides (LPSs) alone
      and in combination with PEITC or CUR to assess their anti-inflammatory and
      antioxidative effects based on gene and protein expression in the treated cells.
      LPS treatment resulted in an increase in the expression of inflammatory markers
      such as cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS),
      interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in both
      Nrf2(+/+) and Nrf2(-/-) macrophages, detected by quantitative polymerase chain
      reaction (qPCR). Nrf2(+/+) macrophages treated with PEITC and CUR exhibited a
      significant decrease in the expression of these anti-inflammatory genes along
      with an increase in the expression of hemeoxygenase-1 (HO-1), which is an
      antioxidative stress gene downstream of the Nrf2 transcription factor battery.
      Although there was no significant decrease in the expression of the anti
      inflammatory genes or an increase in HO-1 expression in Nrf2(-/-) macrophages
      treated with either PEITC or CUR, there was a significant decrease in the protein
      expression of COX-2 and an increase in the expression of HO-1 in Nrf2(+/+)
      macrophages treated with PEITC compared to that with CUR treatment. No
      significant changes were observed in the macrophages from knockout animals.
      Additionally, there was a significant decrease in LPS-induced IL-6 and TNF-alpha
      production following PEITC treatment compared with that following CUR in
      Nrf2(+/+) macrophages, whereas no change was observed in the macrophages from
      knockout animals. The results from qPCR, western blot, and ELISA analyses in
      macrophages from Nrf2(+/+) and Nrf2 (-/-) mice indicate that Nrf2 plays an
      important role in the anti-inflammatory and antioxidative effects of PEITC and
      CUR, as observed by their decreased activities in Nrf2(-/-) macrophages.

PMID- 25387345
TI  - Whole plant foods intake is associated with fewer menopausal symptoms in Chinese
      postmenopausal women with prehypertension or untreated hypertension.
AB  - OBJECTIVE: Nutritional factors have been suggested to be associated with
      menopausal symptoms (MS). However, the role of overall diet in MS has seldom been
      examined in Asian populations. This study aims to examine the association of
      dietary patterns with MS in Chinese postmenopausal women. METHODS: This was a
      cross-sectional study of 726 women with prehypertension or untreated hypertension
      who attended the screening visit for a soy trial. Dietary data were collected
      using a validated food frequency questionnaire containing 85 food items.
      Principal components factor analysis was used to derive dietary patterns based on
      11 food groups. Factors were rotated by orthogonal transformation. Menopause
      related symptoms were assessed by a 20-item validated and structured checklist.
      RESULTS: Three dietary patterns were identified: processed foods, whole plant
      foods, and animal foods. Higher tertile of whole plant foods (P for trend <0.05)
      or lower tertile of processed foods (P for trend <0.05) was associated with fewer
      MS in a dose-dependent manner. Multivariate linear regression analyses showed
      that whole plant foods scores were negatively associated with MS scores, even
      after adjustments for a range of potential confounders (P < 0.01). Logistic
      regression analyses showed that whole plant foods intake was associated with a
      significant reduction in risk for nonvasomotor symptoms only. CONCLUSIONS: Our
      study demonstrates that high intake of whole plant foods is independently
      associated with fewer nonspecific MS. Further evidence from well-designed
      prospective studies is required to confirm this finding.

PMID- 25387346
TI  - Trends in bilateral salpingo-oophorectomy among Taiwanese women undergoing benign
      hysterectomy: a population-based, pooled, cross-sectional study.
AB  - OBJECTIVE: This study aims to examine recent trends in the performance of
      elective bilateral salpingo-oophorectomy at benign hysterectomy and to identify
      associated patient and provider-related characteristics from 2000 to 2010.
      METHODS: We conducted a population-based, pooled, cross-sectional study using
      claims data from Taiwan's National Health Insurance program. Women aged 20 years
      or older who underwent concurrent oophorectomy at benign hysterectomy (n =
      26,419) were compared with women who did not undergo concurrent oophorectomy at
      benign hysterectomy (n = 153,793). A generalized estimating equation model was
      applied to logistic regressions, and separate models were estimated to account
      for age interactions. RESULTS: The overall oophorectomy rate declined steadily
      from 22.1% in 2000 to 9.9% in 2010, particularly in women aged 45 to 49 years
      (decreased by 80%). Women aged 55 years or older who had a comorbid illness or a
      catastrophic illness, underwent abdominal or laparoscopic surgical operation, and
      were admitted to regional hospitals or medical centers were more likely to
      undergo oophorectomy at hysterectomy, whereas women with a preoperative diagnosis
      of uterine prolapse, with a well-defined monthly wage, and undergoing vaginal
      hysterectomy were less likely to undergo oophorectomy. CONCLUSIONS: Age,
      socioeconomic status, presence of comorbid illness, hysterectomy approach,
      hospital accreditation level, and disease diagnosis influence oophorectomy rate
      in Taiwan, a country with national health insurance. Studies on the possible long
      term health risks of elective oophorectomy and the emergence of increasing
      evidence on ovarian cancers of serous histology (such as tubal carcinoma) since
      the early 2000s may have influenced patients' and physicians' decision-making in
      favor of ovarian conservation, leading to the observed downward trend among
      Taiwanese women from 2000 to 2010.

PMID- 25387347
TI  - What are the concerns about custom-compounded "bioidentical" hormone therapy?
AB  - Unsubstantiated claims, lack of scientific safety and efficacy data, and lack of
      quality control surround custom-compounded bioidentical hormone products. FDA
      approved hormone therapy provides tested and regulated therapy without the risks
      of unregulated and untested custom preparations. 

PMID- 25387349
TI  - Cognitive estimations as a measure of executive dysfunction in childhood
      epilepsy.
AB  - Children and adolescents with epilepsy are known to demonstrate executive
      function deficits. Despite prior work that has shown that cognitive estimation
      tasks are sensitive to executive dysfunction in children, such tasks have not
      been studied in children with epilepsy. This is particularly important given the
      fact that executive tasks have heretofore shown poor ecological validity, and it
      has been speculated that estimation tasks may show stronger ecological validity
      than other executive tests. One hundred and thirteen clinically referred children
      and adolescents with epilepsy were included. The Biber Cognitive Estimations Test
      was sensitive to cognitive dysfunction, with about half showing impairments on
      this task in comparison to age-matched normative data; the most frequently
      impaired subscales were quantity estimation and time estimation. Moreover, the
      Biber Cognitive Estimation Test showed moderate correlations with not only
      overall intellectual functions and academic achievement but also other commonly
      administered tests of executive functions, including digit span, Trailmaking, and
      the Tower of London but not with the contingency naming test. Cognitive
      estimations were also modestly correlated with age of epilepsy onset but not
      other epilepsy-severity variables such as number of antiepilepsy drugs (AEDs) or
      seizure frequency. Unfortunately, the hypothesis that the Biber Cognitive
      Estimation Test would show strong ecological validity was not supported, as it
      showed weak relations with parent-reported executive function deficits. The
      significance and limitations of this investigation are discussed. 

PMID- 25387348
TI  - Alterations in gene expression and DNA methylation during murine and human lung
      alveolar septation.
AB  - DNA methylation, a major epigenetic mechanism, may regulate coordinated
      expression of multiple genes at specific time points during alveolar septation in
      lung development. The objective of this study was to identify genes regulated by
      methylation during normal septation in mice and during disordered septation in
      bronchopulmonary dysplasia. In mice, newborn lungs (preseptation) and adult lungs
      (postseptation) were evaluated by microarray analysis of gene expression and
      immunoprecipitation of methylated DNA followed by sequencing (MeDIP-Seq). In
      humans, microarray gene expression data were integrated with genome-wide DNA
      methylation data from bronchopulmonary dysplasia versus preterm and term lung.
      Genes with reciprocal changes in expression and methylation, suggesting
      regulation by DNA methylation, were identified. In mice, 95 genes with inverse
      correlation between expression and methylation during normal septation were
      identified. In addition to genes known to be important in lung development (Wnt
      signaling, Angpt2, Sox9, etc.) and its extracellular matrix (Tnc, Eln, etc.),
      genes involved with immune and antioxidant defense (Stat4, Sod3, Prdx6, etc.)
      were also observed. In humans, 23 genes were differentially methylated with
      reciprocal changes in expression in bronchopulmonary dysplasia compared with
      preterm or term lung. Genes of interest included those involved with detoxifying
      enzymes (Gstm3) and transforming growth factor-beta signaling (bone morphogenetic
      protein 7 [Bmp7]). In terms of overlap, 20 genes and three pathways methylated
      during mouse lung development also demonstrated changes in methylation between
      preterm and term human lung. Changes in methylation correspond to altered
      expression of a number of genes associated with lung development, suggesting that
      DNA methylation of these genes may regulate normal and abnormal alveolar
      septation. 

PMID- 25387350
TI  - Amino acid derivatives of ligustrazine-oleanolic acid as new cytotoxic agents.
AB  - A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed,
      and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester
      bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29,
      Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by
      means of computer simulation, and logP values of both 3beta-glycine ester olean
      12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were
      determined using a shake flask-ultraviolet spectrophotometry method. It was found
      that 6a and the 3beta-L-lysine ester-6g not only displayed good cytotoxicity
      (IC50<3.5 MUM) but also possessed better hydrophilicity than TOA. Moreover, 6a
      (IC50=4.884 MUM) had lower nephrotoxicity than both 6g (IC50=2.310 MUM) and
      cisplatin (CDDP, IC50=3.691 MUM) on MDCK cells. Combining Giemsa and DAPI
      staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei
      fragmentation and had lower nephrotoxicity. In addition, the structure-activity
      relationships of these derivatives are briefly discussed.

PMID- 25387351
TI  - Sulfated chitosan oligosaccharides suppress LPS-induced NO production via JNK and
      NF-kappaB inactivation.
AB  - Various biological effects have been reported for sulfated chitosan
      oligosaccharides, but the molecular mechanisms of action of their anti
      inflammatory effects are still unknown. This study aimed to evaluate the anti
      inflammatory effects of sulfated chitosan oligosaccharides and to elucidate the
      possible mechanisms of action. The results showed that pretreated low molecular
      weight sulfated chitosan oligosaccharides inhibited the production of nitric
      oxide (NO) and inflammatory cytokines such as IL-6 and TNF-alpha in
      lipopolysaccharide (LPS)-activated RAW264.7 cells. The sulfated chitosan
      oligosaccharides also suppressed inducible nitric oxide synthase (iNOS),
      phosphorylation of JNK and translocation of p65, a subunit of NF-kappaB, into the
      nucleus by inhibiting degradation of IkappaB-alpha. Our investigation suggests
      sulfated chitosan oligosaccharides inhibit IL-6/TNF-alpha in LPS-induced
      macrophages, regulated by mitogen-activated protein kinases (MAPKs) pathways
      dependent on NF-kappaB activation. 

PMID- 25387352
TI  - Spectroscopic investigation of the mechanism of photocatalysis.
AB  - Reaction mechanisms of various kinds of photocatalysts have been reviewed based
      on the recent reports, in which various spectroscopic techniques including
      luminol chemiluminescence photometry, fluorescence probe method, electron spin
      resonance (ESR), and nuclear magnetic resonance (NMR) spectroscopy were applied.
      The reaction mechanisms elucidated for bare and modified TiO2 were described
      individually. The modified visible light responsive TiO2 photocatalysts, i.e.,
      Fe(III)-deposited metal-doped TiO2 and platinum complex-deposited TiO2, were
      studied by detecting paramagnetic species with ESR, *O2- (or H2O2) with
      chemiluminescence photometry, and OH radicals with a fluorescence probe method.
      For bare TiO2, the difference in the oxidation mechanism for the different
      crystalline form was investigated by the fluorescence probe method, while the
      adsorption and decomposition behaviors of several amino acids and peptides were
      investigated by 1H-NMR spectroscopy. 

PMID- 25387353
TI  - Does genetic variation influence response to treatment with vascular endothelial
      growth factor inhibitors in neovascular age-related macular degeneration?

PMID- 25387355
TI  - Interfacial catalysis of aldol reactions by prolinamide surfactants in reverse
      micelles.
AB  - L-Proline and their derivatives are among the most important class of organic
      catalysts. Three prolinamide surfactants were designed and synthesized. Although
      the surfactants carried identical catalytic groups, their headgroups contained
      different functionalities that affected their ability to self-assemble under
      reverse micelle conditions and hydrogen-bond with the reactants. The surfactant
      with a zwitterionic headgroup capable of strong aggregation was found to have the
      highest activity. The self-association of the surfactants played critical roles
      in the enhanced activity. The location of the catalytic groups at the
      surfactant/polar solvent interface also endowed unusual selectivity in the
      catalyzed aldol reactions.

PMID- 25387354
TI  - Functional near-infrared spectroscopy reveals reduced interhemispheric cortical
      communication after pediatric concussion.
AB  - Concussion, or mild traumatic brain injury (mTBI), is a growing concern,
      especially among the pediatric population. By age 25, as many as 30% of the
      population are likely to have had a concussion. Many result in long-term
      disability, with some evolving to postconcussion syndrome. Treatments are being
      developed, but are difficult to assess given the lack of measures to
      quantitatively monitor concussion. There is no accepted quantitative imaging
      metric for monitoring concussion. We hypothesized that because cognitive function
      and fiber tracks are often impacted in concussion, interhemispheric brain
      communication may be impaired. We used functional near-infrared spectroscopy
      (fNIRS) to quantify functional coherence between the left and right motor cortex
      as a marker of interhemispheric communication. Studies were undertaken during the
      resting state and with a finger-tapping task to activate the motor cortex.
      Pediatric patients (ages 12-18) had symptoms for 31-473 days, compared to
      controls, who have not had reported a previous concussion. We detected
      differences between patients and controls in coherence between the contralateral
      motor cortices using measurements of total hemoglobin and oxy-hemoglobin with a
      p<0.01 (n=8, control; n=12 mTBI). Given the critical need for a quantitative
      biomarker for recovery after a concussion, we present these data to highlight the
      potential of fNIRS coupled with interhemispheric coherence analysis as a
      biomarker of concussion injury. 

PMID- 25387356
TI  - Human serum albumin-TRAIL conjugate for the treatment of rheumatoid arthritis.
AB  - Albumin conjugation is viewed as an effective means of protracting short in vivo
      lifespans of proteins and targeting rheumatoid arthritis (RA). In this study, we
      present a human serum albumin (HSA) conjugate linked with tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) via a bifunctional PEG derivative (HSA
      TRAIL). Prepared HSA-TRAIL was found to have a larger molecular size (~240 kDa,
      15.4 nm) than TRAIL (~66 kDa, 6.2 nm), and its bioactivity (apoptosis,
      cytotoxicity, and antiproliferation) was well preserved in Mia Paca-2 cells and
      mouse splenocytes. The enhanced therapeutic efficacy of HSA-TRAIL was
      demonstrated in collagen-induced arthritis (CIA) mice. The incidence and clinical
      scores, expressed as degree of erythema and swelling in HSA-TRAIL-treated mice,
      were remarkably lower than those of TRAIL-treated mice. The serum levels of pro
      inflammatory cytokines IFN-gamma, TNF-alpha, IL-1beta, and IL-2 in HSA-TRAIL
      treated mice were significantly lower than those of TRAIL-treated mice.
      Furthermore, HSA-TRAIL accumulated in the hind paws of CIA mice, not in naive
      TRAIL mice. Pharmacokinetic profiles of HSA-TRAIL were greatly improved in
      comparison to those of TRAIL (AUCinf: 844.1 +/- 130.0 vs 36.0 +/- 1.2 ng.h/mL;
      t1/2: 6.20 +/- 0.72 vs 0.23 +/- 0.01 h, respectively). The HSA-TRAIL conjugate,
      which presents clear advantages of targeting RA and long systemic circulation by
      HSA and unique anti-inflammatory efficacy by TRAIL, has potential as a novel
      treatment for rheumatoid arthritis. 

PMID- 25387357
TI  - Premovement Changes in Corticospinal Excitability of the Biceps Brachii are Not
      Different Between Arm Cycling and an Intensity-Matched Tonic Contraction.
AB  - The purpose of this study was to determine if supraspinal and/or spinal
      motoneuron excitability of the biceps brachii were differentially modulated
      before: 1) arm cycling and 2) an intensity-matched tonic contraction. Surface EMG
      recordings of motor evoked potentials (MEPs) and cervicomedullary motor evoked
      potentials (CMEPs) were used to assess supraspinal and spinal motoneuron
      excitability, respectively. MEP amplitudes were larger and onset latencies
      shorter, before arm cycling and tonic contraction when compared with rest with no
      intent to move, but with no difference between motor outputs. CMEP amplitudes and
      onset latencies remained unchanged before cycling and tonic contraction compared
      with rest. Premovement enhancement of corticospinal excitability was due to an
      increase in supraspinal excitability that was not task-dependent. This suggests
      that a common neural drive is used to initiate both motor outputs with task
      dependent changes in neural excitability only being evident once the motor
      outputs have begun. 

PMID- 25387358
TI  - Syntheses, structures and properties of two new organic-inorganic hybrid
      materials based on epsilon-Zn Keggin units {epsilon-PMo(V)8Mo(VI)4O(40
      x)(OH)(x)Zn4}.
AB  - Two novel organic-inorganic hybrids, Na[PMo(V)8Mo(VI)4O38(OH)2Zn4][pyim]2.1.5H2O
      [epsilon(pyim)2] (pyim = 2-(2-pyridyl)-imidazole) and
      [PMo(V)8Mo(VI)4O37(OH)3Zn4]2[pyim]6.4H2O [epsilon2(pyim)6], based on epsilon-Zn
      Keggin units {epsilon-PMo(V)8Mo(VI)4O(40-x)(OH)(x)Zn4}, have been successfully
      synthesized under hydrothermal conditions by controlling the pH values.
      Structural analysis indicates that the framework of epsilon(pyim)2 is a 1D chain
      constructed by monomeric epsilon-Zn units modified by pyim ligands, while
      epsilon2(pyim)6 is an isolated structural compound with dimeric epsilon-Zn units
      modified by pyim ligands. This is the first isolated structure of the epsilon
      Keggin POMs system. The luminescent and electrochemical properties of
      epsilon(pyim)2 and epsilon2(pyim)6 were investigated. epsilon2(pyim)6 also shows
      high catalytic activity for the esterification of phosphoric acid with equimolar
      lauryl alcohol to monoalkyl phosphate ester (MAP).

PMID- 25387359
TI  - Evidence that glutathione and the glutathione system efficiently recycle 1-cys
      sulfiredoxin in vivo.
AB  - AIMS: Typical 2-Cys peroxiredoxins (2-Cys Prxs) are Cys peroxidases that undergo
      inactivation by hyperoxidation of the catalytic Cys, a modification reversed by
      ATP-dependent reduction by sulfiredoxin (Srx). Such an attribute is thought to
      provide regulation of 2-Cys Prxs functions. The initial steps of the Srx
      catalytic mechanism lead to a Prx/Srx thiolsulfinate intermediate that must be
      reduced to regenerate Srx. In Saccharomyces cerevisiae Srx, the thiolsulfinate is
      resolved by an extra Cys (Cys48) that is absent in mammalian, plant, and
      cyanobacteria Srxs (1-Cys Srxs). We have addressed the mechanism of reduction of
      1-Cys Srxs using S. cerevisiae Srx mutants lacking Cys48 as a model. RESULTS: We
      have tested the recycling of Srx by glutathione (GSH) by a combination of in
      vitro steady-state and single-turnover kinetic analyses, using enzymatic coupled
      assays, Prx fluorescence, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and reverse-phase chromatography coupled to mass spectrometry.
      We demonstrate that GSH reacts directly with the thiolsulfinate intermediate, by
      following saturation kinetics with an apparent dissociation constant of 34 MUM,
      while producing S-glutathionylated Srx as a catalytic intermediate which is
      efficiently reduced by the glutaredoxin/glutathione reductase system. Total
      cellular depletion of GSH impacted the recycling of Srx, confirming in vivo that
      GSH is the physiologic reducer of 1-Cys Srx. INNOVATION: Our study suggests that
      GSH binds to the thiolsulfinate complex, thus allowing non-rate limiting
      reduction. Such a structural recognition of GSH enables an efficient catalytic
      reduction, even at very low GSH cellular levels. CONCLUSION: This study provides
      both in vitro and in vivo evidence of the role of GSH as the primary reducer of 1
      Cys Srxs.

PMID- 25387362
TI  - Photosensitized E/Z isomerization of (all-E)-lycopene aiming at practical
      applications.
AB  - Photoisomerization of (all-E)-lycopene to the corresponding Z-isomers was
      investigated under visible to middle-infrared light irradiation in the presence
      of several sensitizers, including edible ones. Highly purified (all-E)-lycopene
      from tomato paste was isomerized to Z-isomers to the extent of 46.4-57.4% after
      irradiation with the sensitizers for 60 min in acetone, in which a
      thermodynamically stable isomer of (5Z)-lycopene was predominantly generated,
      whereas kinetically preferable (9Z)- and (13Z)-lycopenes were dominant without
      sensitizer. Examination of the time course of photoisomerization demonstrated
      that the highest isomerization efficiency (80.4%) was attained using erythrosine
      as the sensitizer under 480-600 nm light irradiation in hexane for 60 min, a
      protocol that successfully suppressed the degradation of lycopene. (5Z)-Lycopene,
      reported as a more bioavailable isomer, was again predominantly produced with
      erythrosine and rose bengal in each solvent. 

PMID- 25387361
TI  - Pre-hematopoietic stem cell transplant lung function and pulmonary complications
      in children.
AB  - RATIONALE: Pulmonary complications are a significant cause of morbidity and
      mortality after allogeneic hematopoietic stem cell transplantation. OBJECTIVES:
      The relationship between pretransplant pulmonary function tests (PFTs) and
      development of post-transplant pulmonary complications in children was studied.
      METHODS: This is a retrospective single institution cohort study of 410 patients
      who underwent pretransplant PFT and were monitored to 10 years posttransplant.
      MEASUREMENTS AND MAIN RESULTS: Pulmonary complications were observed in 174 (42%)
      patients. Children with pulmonary complications had significantly lower forced
      expiratory flow at 25-75% of vital capacity (P = 0.02) derived using conventional
      predicted equations for age, and the Global Lung Initiative-2012 predicted
      equations (P = 0.01). T-cell depletion (P = 0.001), acute grade 3-4 graft-versus
      host disease (P = 0.008), and chronic graft-versus-host disease (P = 0.01)
      increased risk for pulmonary complications. Patients who had pulmonary
      complications had a 2.8-fold increased risk of mortality (P < 0.0001). The
      cumulative incidence of death due to pulmonary complications was significantly
      higher in children who had low lung volumes, FRC less than 50% (P = 0.005), TLC
      less than 50% (P = 0.0002), residual volume less than 50% (P = 0.007), and T-cell
      depletion (P = 0.01). Lower FEV1 (P = 0.0005), FVC (P = 0.0005), TLC (P  < 
      0.0001), residual volume less than 50% (P = 0.01), and restrictive lung disease
      (P = 0.01) predicted worse overall survival. CONCLUSIONS: Abnormal pretransplant
      PFT significantly increased risk after transplant. These patients may benefit
      from modified transplant strategies to reduce morbidity and mortality.

PMID- 25387364
TI  - Optimization of medium composition for erythritol production from glycerol by
      Yarrowia lipolytica using response surface methodology.
AB  - Several factors affecting erythritol production from glycerol by Yarrowia
      lipolytica Wratislavia K1 strain were examined in batch fermentations. Ammonium
      sulfate, monopotassium phosphate, and sodium chloride were identified as critical
      medium components that determine the ratio of polyols produced. The central
      composite rotatable experimental design was used to optimize medium composition
      for erythritol production. The concentrations of ammonium sulfate, monopotassium
      phosphate, and sodium chloride in the optimized medium were 2.25, 0.22, and 26.4
      g L(-1), respectively. The C:N ratio was found as 81:1. In the optimized medium
      with 100 g L(-1) of glycerol the Wratislavia K1 strain produced 46.9 g L(-1) of
      erythritol, which corresponded to a 0.47 g g(-1) yield and a productivity of 0.85
      g L(-1) hr(-1). In the fed-batch mode and medium with the total concentration of
      glycerol at 300 g L(-1) and C:N ratio at 81:1, 132 g L(-1) of erythritol was
      produced with 0.44 g g(-1) yield and a productivity of 1.01 g L(-1) hr(-1.) 

PMID- 25387363
TI  - ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves
      metabolic control and neuropathic symptoms in patients with type 2 diabetes.
AB  - Although erythropoietin ameliorates experimental type 2 diabetes with neuropathy,
      serious side effects limit its potential clinical use. ARA 290, a
      nonhematopoietic peptide designed from the structure of erythropoietin, interacts
      selectively with the innate repair receptor that mediates tissue protection. ARA
      290 has shown efficacy in preclinical and clinical studies of metabolic control
      and neuropathy. To evaluate the potential activity of ARA 290 in type 2 diabetes
      and painful neuropathy, subjects were enrolled in this phase 2 study. ARA 290 (4
      mg) or placebo were self-administered subcutaneously daily for 28 d and the
      subjects followed for an additional month without further treatment. No potential
      safety issues were identified. Subjects receiving ARA 290 exhibited an
      improvement in hemoglobin A(1c) (Hb A(1c)) and lipid profiles throughout the 56 d
      observation period. Neuropathic symptoms as assessed by the PainDetect
      questionnaire improved significantly in the ARA 290 group. Mean corneal nerve
      fiber density (CNFD) was reduced significantly compared with normal controls and
      subjects with a mean CNFD >1 standard deviation from normal showed a significant
      increase in CNFD compared with no change in the placebo group. These observations
      suggest that ARA 290 may benefit both metabolic control and neuropathy in
      subjects with type 2 diabetes and deserves continued clinical evaluation.

PMID- 25387387
TI  - Medicare and Medicaid programs: Hospital Outpatient Prospective Payment and
      Ambulatory Surgical Center Payment Systems and Quality Reporting Programs;
      physician-owned hospitals: data sources for expansion exception; physician
      certification of inpatient hospital services; Medicare Advantage organizations
      and Part D sponsors: CMS-identified overpayments associated with submitted
      payment data. Final rule with comment period.
AB  - This final rule with comment period revises the Medicare hospital outpatient
      prospective payment system (OPPS) and the Medicare ambulatory surgical center
      (ASC) payment system for CY 2015 to implement applicable statutory requirements
      and changes arising from our continuing experience with these systems. In this
      final rule with comment period, we describe the changes to the amounts and
      factors used to determine the payment rates for Medicare services paid under the
      OPPS and those paid under the ASC payment system. In addition, this final rule
      with comment period updates and refines the requirements for the Hospital
      Outpatient Quality Reporting (OQR) Program and the ASC Quality Reporting (ASCQR)
      Program. In this document, we also are making changes to the data sources
      permitted for expansion requests for physician-owned hospitals under the
      physician self-referral regulations; changes to the underlying authority for the
      requirement of an admission order for all hospital inpatient admissions and
      changes to require physician certification for hospital inpatient admissions only
      for long-stay cases and outlier cases; and changes to establish a formal process,
      including a three-level appeals process, to recoup overpayments that result from
      the submission of erroneous payment data by Medicare Advantage (MA) organizations
      and Part D sponsors in the limited circumstances in which the organization or
      sponsor fails to correct these data.

PMID- 25387392
TI  - Differences in coreceptor specificity contribute to alternative tropism of HIV-1
      subtype C for CD4(+) T-cell subsets, including stem cell memory T-cells.
AB  - BACKGROUND: CD4(+) memory T-cells are a major target for infection by HIV-1,
      whereby latent provirus can establish and endure suppressive antiretroviral
      therapies. Although HIV-1 subtype C strains (C-HIV) account for the majority of
      HIV-1 infections worldwide, the susceptibility of CD4(+) memory T-cells to
      infection by CCR5- (R5) and CXCR4-using (X4) C-HIV is unknown. Here, we
      quantified the susceptibility of naive and memory CD4(+) T-cell subsets,
      including stem cell memory T-cells (TSCM), to infection by HIV-1 subtype C (C
      HIV) strains from treatment-naive subjects who progressed from chronic to
      advanced stages of disease whilst either maintaining CCR5-using (R5) viruses
      (subjects 1503 and 1854), or who experienced emergence of dominant CXCR4-using
      (X4) strains (subject 1109). FINDINGS: We show that R5 and X4 C-HIV viruses
      preferentially target memory and naive CD4(+) T-cell subsets, respectively. While
      TSCM were susceptible to infection by both R5 and X4 C-HIV viruses, the
      proportion of infected CD4(+) T-cells that were TSCM was higher for R5 strains.
      Mutagenesis studies of subject 1109 viruses established the V3 region of env as
      the determinant underlying the preferential targeting of naive CD4(+) T-cells by
      emergent X4 C-HIV variants in this subject. In contrast, the tropism of R5 C-HIV
      viruses for CD4(+) T-cell subsets was maintained from chronic to advanced stages
      of disease in subjects 1503 and 1854. CONCLUSIONS: This study provides new
      insights into the natural history of tropism alterations for CD4(+) T-cell
      subsets by C-HIV strains during progression from chronic to advanced stages of
      infection. Although not preferentially targeted, our data suggest that TSCM and
      other memory CD4(+) T-cells are likely to be viral reservoirs in subjects with X4
      C-HIV infection.

PMID- 25387393
TI  - Suppression of the FOXM1 transcriptional programme via novel small molecule
      inhibition.
AB  - The transcription factor FOXM1 binds to sequence-specific motifs on DNA
      (C/TAAACA) through its DNA-binding domain (DBD) and activates proliferation- and
      differentiation-associated genes. Aberrant overexpression of FOXM1 is a key
      feature in oncogenesis and progression of many human cancers. Here--from a high
      throughput screen applied to a library of 54,211 small molecules--we identify
      novel small molecule inhibitors of FOXM1 that block DNA binding. One of the
      identified compounds, FDI-6 (NCGC00099374), is characterized in depth and is
      shown to bind directly to FOXM1 protein, to displace FOXM1 from genomic targets
      in MCF-7 breast cancer cells, and induce concomitant transcriptional
      downregulation. Global transcript profiling of MCF-7 cells by RNA-seq shows that
      FDI-6 specifically downregulates FOXM1-activated genes with FOXM1 occupancy
      confirmed by ChIP-PCR. This small molecule-mediated effect is selective for FOXM1
      controlled genes with no effect on genes regulated by homologous forkhead family
      factors.

PMID- 25387394
TI  - Diagnostic value of PSA and AP tests for the detection of spermatozoa in
      postmortem swabs from the genital and anal region in males.
AB  - The aim of this study was to clarify whether positive results for prostate
      specific antigen (PSA) and acid phosphatase (AP) occur in postmortem swabs from
      the genito-anal region in males (n = 80; 4 regions) and females (n = 20; 3
      regions) and to calculate the positive predictive value (PPV) concerning the
      presence of spermatozoa. In male subjects, the highest incidence of positive test
      results was found in urethral swabs (PSA 76%, AP 71%) and the lowest frequencies
      appeared in perianal and rectal swabs (15-20%). Microscopic evaluation for
      spermatozoa was positive between 39% in urethral swabs and 1% in rectal swabs.
      PPV regarding positive identification of spermatozoa was 33.3% for PSA and 31.5%
      for AP. The combination of both tests yielded a PPV of 38.2%. In female cases, no
      spermatozoa were identified, and one case was PSA- and AP-positive in perianal
      swabs. Our findings indicate that PSA and AP tests are of limited value for the
      postmortem detection of spermatozoa in male subjects.

PMID- 25387396
TI  - A highly efficient nonchemical method for isolating live nematodes
      (Caenorhabditis elegans) from soil during toxicity assays.
AB  - The success of soil toxicity tests using Caenorhabditis elegans may depend in
      large part on recovering the organisms from the soil. However, it can be
      difficult to learn the International Organization for Standardization/ASTM
      International recovery process that uses the colloidal silica flotation method.
      The present study determined that a soil-agar isolation method provides a highly
      efficient and less technically demanding alternative to the colloidal silica
      flotation method. Test soil containing C. elegans was arranged on an agar plate
      in a donut shape, a linear shape, or a C curve; and microbial food was placed
      outside the soil to encourage the nematodes to leave the soil. The effects of
      ventilation and the presence of food on nematode recovery were tested to
      determine the optimal conditions for recovery. A linear arrangement of soil on an
      agar plate that was sprinkled with microbial food produced nearly 83% and 90%
      recovery of live nematodes over a 3-h and a 24-h period, respectively, without
      subjecting the nematodes to chemical stress. The method was tested using copper
      (II) chloride dihydrate, and the resulting recovery rate was comparable to that
      obtained using colloidal silica flotation. The soil-agar isolation method
      portrayed in the present study enables live nematodes to be isolated with minimal
      additional physicochemical stress, making it a valuable option for use in
      subsequent sublethal tests where live nematodes are required.

PMID- 25387397
TI  - Extracellular matrix: Preconditioning the ECM for fibrosis.

PMID- 25387395
TI  - A developmentally inspired combined mechanical and biochemical signaling approach
      on zonal lineage commitment of mesenchymal stem cells in articular cartilage
      regeneration.
AB  - Articular cartilage is organized into multiple zones including superficial,
      middle and calcified zones with distinct cellular and extracellular components to
      impart lubrication, compressive strength, and rigidity for load transmission to
      bone, respectively. During native cartilage tissue development, changes in
      biochemical, mechanical, and cellular factors direct the formation of stratified
      structure of articular cartilage. The objective of this work was to investigate
      the effect of combined gradients in cell density, matrix stiffness, and zone
      specific growth factors on the zonal organization of articular cartilage. Human
      mesenchymal stem cells (hMSCs) were encapsulated in acrylate-functionalized
      lactide-chain-extended polyethylene glycol (SPELA) gels simulating cell density
      and stiffness of the superficial, middle and calcified zones. The cell
      encapsulated gels were cultivated in a medium supplemented with growth factors
      specific to each zone and the expression of zone-specific markers was measured
      with incubation time. Encapsulation of 60 * 10(6) cells per mL hMSCs in a soft
      gel (80 kPa modulus) and cultivation with a combination of TGF-beta1 (3 ng mL(
      1)) and BMP-7 (100 ng mL(-1)) led to the expression of markers for the
      superficial zone. Conversely, encapsulation of 15 * 10(6) cells per mL hMSCs in a
      stiff gel (320 MPa modulus) and cultivation with a combination of TGF-beta1 (30
      ng mL(-1)) and hydroxyapatite (3%) led to the expression of markers for the
      calcified zone. Further, encapsulation of 20 * 10(6) cells per mL hMSCs in a gel
      with 2.1 MPa modulus and cultivation with a combination of TGF-beta1 (30 ng mL(
      1)) and IGF-1 (100 ng mL(-1)) led to up-regulation of the middle zone markers.
      Results demonstrate that a developmental approach with gradients in cell density,
      matrix stiffness, and zone-specific growth factors can potentially regenerate
      zonal structure of the articular cartilage. 

PMID- 25387398
TI  - Stem cells: Insulin-producing beta cells in a dish.

PMID- 25387399
TI  - Science and technology consortia in U.S. biomedical research: a paradigm shift in
      response to unsustainable academic growth.

PMID- 25387401
TI  - Next generation sequencing and FISH reveal uneven and nonrandom microsatellite
      distribution in two grasshopper genomes.
AB  - Simple sequence repeats (SSRs), also known as microsatellites, are one of the
      prominent DNA sequences shaping the repeated fraction of eukaryotic genomes. In
      spite of their profuse use as molecular markers for a variety of genetic and
      evolutionary studies, their genomic location, distribution, and function are not
      yet well understood. Here we report the first thorough joint analysis of
      microsatellite motifs at both genomic and chromosomal levels in animal species,
      by a combination of 454 sequencing and fluorescent in situ hybridization (FISH)
      techniques performed on two grasshopper species. The in silico analysis of the
      454 reads suggested that microsatellite expansion is not driving size increase of
      these genomes, as SSR abundance was higher in the species showing the smallest
      genome. However, the two species showed the same uneven and nonrandom location of
      SSRs, with clear predominance of dinucleotide motifs and association with several
      types of repetitive elements, mostly histone gene spacers, ribosomal DNA
      intergenic spacers (IGS), and transposable elements (TEs). The FISH analysis
      showed a dispersed chromosome distribution of microsatellite motifs in
      euchromatic regions, in coincidence with chromosome location patterns previously
      observed for many mobile elements in these species. However, some SSR motifs were
      clustered, especially those located in the histone gene cluster. 

PMID- 25387403
TI  - Investigation of copy number variation in children with conotruncal heart
      defects.
AB  - BACKGROUND: Congenital heart defects (CHD) are the most prevalent group of
      structural abnormalities at birth and one of the main causes of infant morbidity
      and mortality. Studies have shown a contribution of the copy number variation in
      the genesis of cardiac malformations. OBJECTIVES: Investigate gene copy number
      variation (CNV) in children with conotruncal heart defect. METHODS: Multiplex
      ligation-dependent probe amplification (MLPA) was performed in 39 patients with
      conotruncal heart defect. Clinical and laboratory assessments were conducted in
      all patients. The parents of the probands who presented abnormal findings were
      also investigated. RESULTS: Gene copy number variation was detected in 7/39
      patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2
      duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication.
      The clinical characteristics were consistent with those reported in the
      literature associated with the encountered microdeletion/microduplication. None
      of these changes was inherited from the parents. CONCLUSIONS: Our results
      demonstrate that the technique of MLPA is useful in the investigation of
      microdeletions and microduplications in conotruncal congenital heart defects.
      Early diagnosis of the copy number variation in patients with congenital heart
      defect assists in the prevention of morbidity and decreased mortality in these
      patients.

PMID- 25387404
TI  - Atrial fibrillation ablation in systolic dysfunction: clinical and
      echocardiographic outcomes.
AB  - BACKGROUND: Heart failure and atrial fibrillation (AF) often coexist in a
      deleterious cycle. OBJECTIVE: To evaluate the clinical and echocardiographic
      outcomes of patients with ventricular systolic dysfunction and AF treated with
      radiofrequency (RF) ablation. METHODS: Patients with ventricular systolic
      dysfunction [ejection fraction (EF) <50%] and AF refractory to drug therapy
      underwent stepwise RF ablation in the same session with pulmonary vein isolation,
      ablation of AF nests and of residual atrial tachycardia, named "background
      tachycardia". Clinical (NYHA functional class) and echocardiographic (EF, left
      atrial diameter) data were compared (McNemar test and t test) before and after
      ablation. RESULTS: 31 patients (6 women, 25 men), aged 37 to 77 years (mean, 59.8
      +/- 10.6), underwent RF ablation. The etiology was mainly idiopathic (19 p, 61%).
      During a mean follow-up of 20.3 +/- 17 months, 24 patients (77%) were in sinus
      rhythm, 11 (35%) being on amiodarone. Eight patients (26%) underwent more than
      one procedure (6 underwent 2 procedures, and 2 underwent 3 procedures).
      Significant NYHA functional class improvement was observed (pre-ablation: 2.23 +/
      0.56; postablation: 1.13 +/- 0.35; p < 0.0001). The echocardiographic outcome
      also showed significant ventricular function improvement (EF pre: 44.68% +/-
      6.02%, post: 59% +/- 13.2%, p = 0.0005) and a significant left atrial diameter
      reduction (pre: 46.61 +/- 7.3 mm; post: 43.59 +/- 6.6 mm; p = 0.026). No major
      complications occurred. CONCLUSION: Our findings suggest that AF ablation in
      patients with ventricular systolic dysfunction is a safe and highly effective
      procedure. Arrhythmia control has a great impact on ventricular function recovery
      and functional class improvement.

PMID- 25387406
TI  - Effect of Pain Induction or Pain Reduction on Conditioned Pain Modulation in
      Adults: A Systematic Review.
AB  - OBJECTIVE: Pain facilitation as well as pain inhibition might be present in
      chronic pain patients. A decreased efficacy of pain inhibition can be measured by
      conditioned pain modulation (CPM). The use of the CPM paradigm in scientific
      research has boosted over the last few years and is recognized for its high
      clinical relevance in chronic pain patients. It is, however, unclear whether the
      presence of pain and possible modulations of pain influences the efficacy of
      endogenous pain inhibition, measured by CPM. This systematic literature study
      aimed to provide an overview of the effects of clinical pain and experimental
      pain induction or pain reduction on CPM in adults. METHODS: A systematic
      literature search was conducted in the databases "Pubmed" and "Web of Science".
      Only full texts of original studies regarding the effect of clinical pain and
      experimentally induced pain and pain reduction on CPM in adults were included.
      The included articles were scored on methodological quality and through a CPM
      paradigm. RESULTS: Twelve articles of good to moderate quality were included in
      this review. Some pain inhibitory medication and oral contraceptives inhibit the
      CPM mechanism. Removing chronic pain by surgery results in an improved CPM
      response. This effect is not observed when removing acute pain. CONCLUSION:
      Analgesic medication and oral contraceptives might inhibit the CPM response,
      whereas there is limited evidence that pain-relieving surgery improves CPM in
      chronic pain patients. However, the results merely suggest that decreased CPM
      values (as in chronic pain patients) can improve after elimination of pain.

PMID- 25387405
TI  - Functional capacity of patients with pacemaker due to isolated congenital
      atrioventricular block.
AB  - BACKGROUND: Isolated congenital atrioventricular block (CAVB) is a rare condition
      with multiple clinical outcomes. Ventricular remodeling can occur in
      approximately 10% of the patients after pacemaker (PM) implantation. OBJECTIVES:
      To assess the functional capacity of children and young adults with isolated CAVB
      and chronic pacing of the right ventricle (RV) and evaluate its correlation with
      predictors of ventricular remodeling. METHODS: This cross-sectional study used a
      cohort of patients with isolated CAVB and RV pacing for over a year. The subjects
      underwent clinical and echocardiographic evaluation. Functional capacity was
      assessed using the six-minute walk test. Chi-square test, Fisher's exact test,
      and Pearson correlation coefficient were used, considering a significance level
      of 5%. RESULTS: A total of 61 individuals were evaluated between March 2010 and
      December 2013, of which 67.2% were women, aged between 7 and 41 years, who were
      using PMs for 13.5 +/- 6.3 years. The percentage of ventricular pacing was 97.9
      +/- 4.1%, and the duration of the paced QRS complex was 153.7 +/- 19.1 ms.
      Majority of the subjects (95.1%) were asymptomatic and did not use any
      medication. The mean distance walked was 546.9 +/- 76.2 meters and was strongly
      correlated with the predicted distance (r = 0.907, p = 0.001) but not with risk
      factors for ventricular remodeling. (Arq Bras Cardiol. 2014; [online].ahead
      print, PP.0-0) CONCLUSIONS: The functional capacity of isolated CAVB patients
      with chronic RV pacing was satisfactory but did not correlate with risk factors
      for ventricular remodeling.

PMID- 25387408
TI  - Electrochemical "read-write" microscale patterning of boron doped diamond
      electrodes.
AB  - Scanning electrochemical cell microscopy is utilised as a read-write pipette
      based probe to both electrochemically modify the local surface chemistry of boron
      doped diamond and "read" the resulting modification, at the micron scale. In this
      specific application, localised electrochemical oxidation results in conversion
      of the H-terminated surface to -O, electrochemically visualised by monitoring the
      current change for reduction of Ru(NH3)6(3+). This methodology, in general,
      provides a platform for read-write analysis of electrodes, opening up new
      analytical avenues, particularly as the pipette can be viewed as a microfluidic
      device. 

PMID- 25387407
TI  - Signaling via PI3K/FOXO1A pathway modulates formation and survival of human
      embryonic stem cell-derived endothelial cells.
AB  - Vascular derivatives of human embryonic stem cells (hESC) are being developed as
      sources of tissue-specific cells for organ regeneration. However, identity of
      developmental pathways that modulate the specification of endothelial cells is
      not known yet. We studied phosphatidylinositol 3-kinase (PI3K)-Forkhead box O
      transcription factor 1A (FOXO1A) pathways during differentiation of hESC toward
      endothelial lineage and on proliferation, maturation, and cell death of hESC
      derived endothelial cells (hESC-EC). During differentiation of hESC, expression
      of FOXO1A transcription factor was linked to the expression of a cluster of
      angiogenesis- and vascular remodeling-related genes. PI3K inhibitor LY294002
      activated FOXO1A and induced formation of CD31(+) hESC-EC. In contrast,
      differentiating hESC with silenced FOXO1A by small interfering RNA (siRNA) showed
      lower mRNA levels of CD31 and angiopoietin2. LY294002 decreased proliferative
      activity of purified hESC-EC, while FOXO1A siRNA increased their proliferation.
      LY294002 inhibits migration and tube formation of hESC-EC; in contrast, FOXO1A
      siRNA increased in vitro tube formation activity of hESC-EC. After in vivo
      conditioning of cells in athymic nude rats, cells retain their low FOXO1A
      expression levels. PI3K/FOXO1A pathway is important for function and survival of
      hESC-EC and in the regulation of endothelial cell fate. Understanding these
      properties of hESC-EC may help in future applications for treatment of injured
      organs. 

PMID- 25387410
TI  - Inflammatory response to heparinoid and heparin in a patient with tumor necrosis
      factor receptor-associated periodic syndrome: the second case with a T61I
      mutation in the TNFRSF1A gene.

PMID- 25387409
TI  - Monitoring of WT1 and its target gene IRF8 expression in acute myeloid leukemia
      and their significance.

PMID- 25387412
TI  - I. An introduction to the relation of physical activity to cognitive and brain
      health, and scholastic achievement.
AB  - The current pandemic of physical inactivity threatens both physical and cognitive
      health throughout the lifespan. This monograph describes the multidisciplinary
      study of aspects of childhood health and its relationship to cognitive and brain
      function, and scholastic performance. Specifically, we focus on physical activity
      and physical fitness along with nutrition and obesity; interconnected aspects of
      health that have declined over the past 30 years in children of industrialized
      nations. Although much emphasis has been placed on correcting physical aspects of
      these public health concerns, it is only more recently that attention has been
      paid to the relation between physical health and cognitive health among school
      age children. The monograph begins with an overview of current behavioral trends
      that compete with physical activity engagement and contribute to the failure to
      achieve the public health recommendations for physical activity among children in
      the United States. Following the epidemiological overview, the relation of
      childhood fitness to brain structure and function is examined among children with
      varying fitness levels. The observed dissimilarities between higher- and lower
      fit children are discussed within the context of typical brain development. To
      broaden the scope of research presented herein, the relation of nutrient intake-
      among both undernourished and well-nourished children--and obesity on cognition
      and brain are discussed. Next, novel empirical data are presented from a
      correlational study that indicates a differential relation between childhood
      fitness and adiposity on various aspects of cognition. In an effort to provide a
      more comprehensive review, a later chapter is dedicated to describing a small
      body of literature investigating the relation of physical activity to special
      populations of children, including those with learning disorders. In doing so,
      practical applications as well as challenges and limitations of implementing
      physical activity into the lives of children with learning disabilities are
      described. Finally, a detailed review and historical analysis of the relation of
      physical activity to scholastic performance is provided. This translational
      chapter provides an important application of the laboratory findings to a real
      world setting in which children rely upon attention, memory, and learning for
      scholastic success. Accordingly, this monograph is directed toward timely and
      important public health issues related to chronic disease prevention as a
      function of childhood inactivity and obesity with the goal of linking health
      behaviors to cognitive and brain health, and scholastic performance.

PMID- 25387411
TI  - Antioxidant effect of lycopene-enriched tomato paste on N-nitrosodiethylamine
      induced oxidative stress in rats.
AB  - Lycopene is a carotenoid pigment produced by vegetables and fruits, with tomatoes
      and their processed products being the most abundant sources. A high number of
      conjugated dienes make lycopene a powerful radical scavenger. Its antioxidant
      properties are considered to be primarily involved in many beneficial health
      effects. The present study was designed to assess the protective effect of
      lycopene-enriched tomato paste against N-nitrosodiethylamine (NDEA)-induced
      oxidative stress in rats. Forty-eight male Wistar rats were divided randomly into
      six groups. Four groups were treated with tomato paste, per os, for 28 days in
      doses which were equivalent to 0.5 (groups II and V) and 2.5 mg/kg b.w./day of
      lycopene (groups III and VI). Rats from groups IV-VI were given intraperitoneally
      a single dose of NDEA, 150 mg/kg b.w. Group I (control) was given distilled
      water. Pretreatment with tomato paste protected the antioxidant enzymes:
      superoxide dismutase, catalase and glutathione reductase. Their activity was
      recovered by 32-97 %, as compared to NDEA-treated rats. Microsomal lipid
      peroxidation in the liver was decreased in rats pretreated with a lower dose of
      tomato paste by 28 %, as compared to animals given NDEA alone. Pretreatment with
      tomato paste caused a decrease in plasma concentration of protein carbonyls, even
      below the control level, in rats given NDEA. Moreover, a 10 % reduction of DNA
      damage in leucocytes caused by NDEA was observed. The tomato paste tested was
      able to suppress NDEA-induced oxidative stress in rats.

PMID- 25387413
TI  - II. Physical activity: measurement and behavioral patterns in children and youth.
AB  - With physical activity levels among children and adolescents at an all-time low,
      there is a critical need for scientists and public health officials alike to
      further examine the physical activity behaviors of this population. Accordingly,
      this chapter will act as an entree to the rest of the monograph by providing a
      general overview of the epidemiology of physical activity among youth in the
      United States. In so doing, we discuss the following: public health guidelines
      for youth-based physical activity, current rates and trends of physical activity
      participation in youth, issues related to physical education rates in school
      systems, lifestyle practices that encourage sedentary behaviors and attendant
      disease states, a synopsis of the health-related benefits of a physically active
      lifestyle, promotion of and opportunities for increased engagement, and
      comparisons of objective and subjective methods of measuring physical activity. 

PMID- 25387414
TI  - III. The importance of physical activity and aerobic fitness for cognitive
      control and memory in children.
AB  - In this chapter, we review literature that examines the association among
      physical activity, aerobic fitness, cognition, and the brain in elementary school
      children (ages 7-10 years). Specifically, physical activity and higher levels of
      aerobic fitness in children have been found to benefit brain structure, brain
      function, cognition, and school achievement. For example, higher fit children
      have larger brain volumes in the basal ganglia and hippocampus, which relate to
      superior performance on tasks of cognitive control and memory, respectively, when
      compared to their lower fit peers. Higher fit children also show superior brain
      function during tasks of cognitive control, better scores on tests of academic
      achievement, and higher performance on a real-world street crossing task,
      compared to lower fit and less active children. The cross-sectional findings are
      strengthened by a few randomized, controlled trials, which demonstrate that
      children randomly assigned to a physical activity intervention group show greater
      brain and cognitive benefits compared to a control group. Because these findings
      suggest that the developing brain is plastic and sensitive to lifestyle factors,
      we also discuss typical structural and functional brain maturation in children to
      provide context in which to interpret the effects of physical activity and
      aerobic fitness on the developing brain. This research is important because
      children are becoming increasingly sedentary, physically inactive, and unfit. An
      important goal of this review is to emphasize the importance of physical activity
      and aerobic fitness for the cognitive and brain health of today's youth. 

PMID- 25387415
TI  - IV. The cognitive implications of obesity and nutrition in childhood.
AB  - The prevalence of childhood obesity in the United States has tripled since the
      1980s and is strongly linked to the early onset of several metabolic diseases.
      Recent studies indicate that lower cognitive function may be another complication
      of childhood obesity. This review considers the research to date on the role of
      obesity and nutrition on childhood cognition and brain health. Although a handful
      of studies point to a maladaptive relationship between obesity and aspects of
      cognitive control, remarkably little is known regarding the impact of fat mass on
      brain development and cognitive function. Further, missing from the literature is
      the role of nutrition in the obesity-cognition interaction. Nutrition may
      directly or indirectly influence cognitive performance via several pathways
      including provision of key substrates for optimal brain health, modulation of gut
      microbiota, and alterations in systemic energy balance. However, in the absence
      of malnutrition, the functional benefits of specific nutrient intake on
      particular cognitive domains are not well characterized. Here, we examine the
      literature linking childhood obesity and cognition while considering the effects
      of nutritional intake. Possible mechanisms for these relationships are discussed
      and suggestions are made for future study topics. Although childhood obesity
      prevalence rates in some developed countries have recently stabilized,
      significant disparities remain among groups based on sex and socioeconomic
      status. Given that the elevated prevalence of pediatric overweight and obesity
      may persist for the foreseeable future, it is crucial to develop a comprehensive
      understanding of the influence of obesity and nutrition on cognition and brain
      health in the pediatric population. 

PMID- 25387416
TI  - V. The differential association of adiposity and fitness with cognitive control
      in preadolescent children.
AB  - With the increasing prevalence of sedentary behaviors during childhood, a greater
      understanding of the extent to which excess adiposity and aerobic fitness relate
      to cognitive health is of increasing importance. To date, however, the vast
      majority of research in this area has focused on adiposity or fitness, rather
      than the possible inter-relationship, as it relates to cognition. Accordingly,
      this study examined the differential associations between body composition,
      aerobic fitness, and cognitive control in a sample of 204 (96 female)
      preadolescent children. Participants completed a modified flanker task (i.e.,
      inhibition) and a switch task (i.e., cognitive flexibility) to assess two aspects
      of cognitive control. Findings from this study indicate that fitness and
      adiposity appear to be separable factors as they relate to cognitive control,
      given that the interaction of fitness and adiposity was observed to be
      nonsignificant for both the flanker and switch tasks. Fitness exhibited an
      independent association with both inhibition and cognitive flexibility whereas
      adiposity exhibited an independent association only with cognitive flexibility.
      These results suggest that while childhood obesity and fitness appear to both be
      related to cognitive control, they may be differentially associated with its
      component processes. 

PMID- 25387417
TI  - VI. The role of physical activity in reducing barriers to learning in children
      with developmental disorders.
AB  - Emerging research suggests that physical activity may be an effective non
      pharmaceutical intervention approach for childhood developmental disorders.
      Findings indicate that both single bouts of activity and chronic physical
      activity associate with improved mental health and classroom performance in
      children with attention-deficit/hyperactivity disorder and children with autism
      spectrum disorders. This review describes the research in this area and
      identifies limitations and challenges to the translation of these findings to
      promote physical activity in clinical practice and educational policy. 

PMID- 25387418
TI  - VII. The history of physical activity and academic performance research:
      informing the future.
AB  - The study of physical activity, physical fitness, and academic performance
      research are reviewed from a historical perspective, by providing an overview of
      existing publications focused on children and adolescents. Using rigorous
      inclusion criteria, the studies were quantified and qualified using both meta
      analytic and descriptive evaluations analyses, first by time-period and then as
      an overall summary, particularly focusing on secular trends and future
      directions. This review is timely because the body of literature is growing
      exponentially, resulting in the emergence of new terminology, methodologies, and
      identification of mediating and moderating factors. Implications and
      recommendations for future research are summarized. 

PMID- 25387419
TI  - VIII. Conclusions and future directions of the research on physical activity and
      childhood cognitive and brain health.
AB  - This chapter serves as a summary to the monograph. The main purpose is to
      concisely merge the individual chapters into a cohesive summary around markers of
      health behaviors and their relation to childhood cognition and brain health. In
      addition, future directions for research in this area are briefly discussed with
      the goal of shaping future research in several directions. Issues surrounding the
      need for causality and ethical considerations are also described. Finally, this
      chapter places the link between health behaviors and cognition within the greater
      context of the educational environment, lifelong health, and effective function. 

PMID- 25387420
TI  - Mechanisms and correlates of a healthy brain: a commentary.
AB  - In this monograph, the message is that early inactivity and obesity lead to later
      chronic disease, and, as such, physical inactivity should be recognized as a
      public health crisis. Sedentary behavior, to some extent, serves a purpose in our
      current culture (e.g., keeping children indoors keeps them safe), and, as such,
      may not be amenable to change. Thus, it is important that we understand the
      underpinnings of later-developing chronic disease as this complex public health
      issue may have roots that go deeper than sedentary behavior. In this commentary,
      I speculate on the mechanisms for physical activity exacting positive changes on
      cognitive abilities. Three potential mechanisms are discussed: glucose transport,
      postnatal neurogenesis, and vitamin synthesis, all of which are inextricably
      linked to nutrition. This discussion of mechanisms is followed by a discussion of
      tractable correlates of the progression to non-communicable disease in the adult.

PMID- 25387424
TI  - Transcriptomics of developing embryos and organs: A raising tool for evo-devo.
AB  - Comparative transcriptomics has become an important tool for revisiting many evo
      devo questions and exploring new ones, and its importance is likely to increase
      in the near future, partly because RNA-seq data open many new possibilities. The
      aim of this opinion piece is twofold. In the first section, we discuss the
      particularities of transcriptomic studies in evo-devo, focusing mainly on RNA-seq
      data. The preliminary processing steps (getting coding sequences as well as
      expression levels) are challenging, because many studied species do not have a
      sequenced genome. The next step (interpreting expression differences) is also
      challenging, due to several issues with interpreting expression levels in complex
      tissues, managing developmental stages and species heterochronies, and the
      problem of conceptualizing expression differences. In the second section, we
      discuss some past and possible future applications of transcriptomic approaches
      (using microarray or RNA-seq) to three major themes in evo-devo: the evolution of
      the developmental toolkit, the genetic and developmental basis for phenotypic
      changes, and the general rules of the evolution of development. We believe that
      conceptual and technical tools are necessary in order to fully exploit the
      richness of multispecies transcriptomic time-series data.

PMID- 25387425
TI  - Sagittal deformities of the spine: factors influencing the outcomes and
      complications.
AB  - Degenerative changes have the potential to greatly disrupt the normal curvature
      of the spine, leading to sagittal malalignment. This phenomenon is often treated
      with operative modalities, such as osteotomies, though even with surgery, only
      one-third of patients may reach neutral alignment. Improvement in surgical
      outcomes may be achieved through better understanding of radiographic spino
      pelvic parameters and their association with deformity. Methodical surgical
      planning, including selection of levels of instrumentation and site of the
      osteotomy, is crucial in determining the optimal plan for a patient's specific
      pathology and may minimize risk of developing postoperative proximal junctional
      kyphosis/failure. While sagittal alignment is essential in operative strategy,
      the coronal plane should not be overlooked, as it may affect the osteotomy
      technique. The concepts of sagittal balance and alignment are further complicated
      in patients with neuromuscular diseases such as Parkinson's disease, and
      appreciation of the interplay between anatomic and postural deformities is
      necessary to properly treat these patients. Finally, given the importance of
      sagittal alignment and the role of osteotomies in treatment for deformity, the
      need for future research becomes apparent. Novel intraoperative measurement
      techniques and three-dimensional analysis of the spine may allow for vastly
      improved operative correction. Furthermore, awareness of the relationship between
      alignment and balance, the soft tissue envelope, and compensatory mechanisms will
      provide a more comprehensive conception of the nature of spinal deformity and the
      modalities with which it is treated. 

PMID- 25387426
TI  - Cervical osteotomies for neurological deformities.
AB  - PURPOSE: To report our experience and technique for performing cervical
      osteotomies under the setting of cervical deformity and myelopathy. METHODS:
      Patients who underwent cervical osteotomies for CD with myelopathy were
      identified in a 10 year period from 2000 to 2010. Demographics, surgery type,
      osteotomy type, operative details, and radiographs were collected for pre
      operative and ultimate post-operative time points. Cervical lordosis (CL) and
      basion plumb line were collected to assess angular and translational corrections.
      RESULTS: In the study period, a total of 35 patients underwent a cervical
      osteotomy for fixed cervical deformity with a diagnosis of cervical myelopathy or
      myeloradiculopathy with an average follow-up of 3.4 years (range 1.0-6.3). The
      cohort was separated into two groups based on the type of surgical approach taken
      to correct their deformity. Anterior osteotomy with or without posterior
      instrumentation were performed in 31 patients (Group 1). Pedicle subtraction
      osteotomies were performed in 4 patients (Group 2). For Group 1, the mean angular
      correction achieved in this was 27.7 degrees  (range 9.0-66.0 degrees ) and the
      mean translational correction was 1.8 cm (range 0.1-2.4 cm). In group 2, the mean
      angular correction was 48.8 degrees  (range 38.4-68.3 degrees ) and the mean
      translational correction was 2.8 cm per PSO (range 0.1-5.6 cm). Similar
      improvements in pre- and post-operative Neck Disability Index scores were
      achieved with either osteotomy technique. CONCLUSIONS: We present our series of
      patients with cervical myelopathy and/or radiculopathy and concurrent cervical
      deformity who were treated with cervical osteotomies. The re-alignment of the
      spine was a key step in preventing the progression of myelopathy and protecting
      the spinal cord from the continued injury.

PMID- 25387427
TI  - Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic
      and syngeneic transplants.
AB  - Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells
      (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts
      within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+)
      ("LSK") cells, a classic signature for HSCs, were also detected among these graft
      infiltrating cells. Lineage negative graft infiltrating cells are functionally
      multi-potential as determined by a standard competitive bone marrow transplant
      (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative
      HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating
      cells, differentiate and repopulate multiple mature blood cell phenotypes in
      peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts.
      Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as
      well as allogeneic cardiac transplants and sham surgery sites. It seems likely
      that an inflammatory response, not an adaptive immune response to allo-antigen,
      is responsible for the rapid infiltration of islet and cardiac transplants by
      biologically active HSCs/HPCs. The pattern of hematopoietic differentiation
      obtained from graft infiltrating HSCs/HPCs, cells that are recovered from
      inflammatory sites, as noted in the competitive BMT assay, is not precisely the
      same as that of intramedullary HSCs. This does not refute the obvious multi
      lineage potential of graft infiltrating HSCs/HPCs. 

PMID- 25387428
TI  - The effect of intra-operative transcutaneous electrical nerve stimulation on
      posterior neck pain following thyroidectomy.
AB  - Posterior neck pain following thyroidectomy is common because full neck extension
      is required during the procedure. We evaluated the effect of intra-operative
      transcutaneous electrical nerve stimulation on postoperative neck pain in
      patients undergoing total thyroidectomy under general anaesthesia. One hundred
      patients were randomly assigned to one of two groups; 50 patients received
      transcutaneous electrical nerve stimulation applied to the trapezius muscle and
      50 patients acted as controls. Postoperative posterior neck pain and anterior
      wound pain were evaluated using an 11-point numerical rating scale at 30 min, 6
      h, 24 h and 48 h following surgery. The numerical rating scale for posterior neck
      pain was significantly lower in the transcutaneous electrical nerve stimulation
      group compared with the control group at all time points (p < 0.05). There were
      no significant differences in the numerical rating scale for anterior wound pain
      at any time point. No adverse effects related to transcutaneous electrical nerve
      stimulation were observed. We conclude that intra-operative transcutaneous
      electrical nerve stimulation applied to the trapezius muscle reduced posterior
      neck pain following thyroidectomy. 

PMID- 25387429
TI  - Extreme tolerance and developmental buffering of UV-C induced DNA damage in
      embryos of the annual killifish Austrofundulus limnaeus.
AB  - Free-living aquatic embryos are often at risk of exposure to ultraviolet
      radiation (UV-R). Successful completion of embryonic development depends on
      efficient removal of DNA lesions, and thus many aquatic embryos have mechanisms
      to reverse DNA lesions induced by UV-R. However, little is known of how embryos
      that are able to enter embryonic dormancy may respond to UV-R exposure and
      subsequent DNA damage. Embryos of the annual killifish Austrofundulus limnaeus
      are unique among vertebrates because their normal embryonic development includes
      (1) a complete dispersion of embryonic blastomeres prior to formation of the
      definitive embryonic axis, and (2) entry into a state of metabolic depression and
      developmental arrest termed diapause. Here, we show that developing and
      diapausing embryos of A. limnaeus have exceptional tolerance of UV-C radiation
      and can successfully complete embryonic development after receiving substantial
      doses of UV-C, especially if allowed to recover in full-spectrum light. Recovery
      in full-spectrum light permits efficient removal of the most common type of DNA
      lesion induced by UV-R: cyclobutane pyrimidine dimers. Interestingly, whole-mount
      embryo TUNEL assays suggest that apoptosis may not be a major contributor to cell
      death in embryos UV-C irradiated during dispersion/reaggregation or diapause. We
      also observed embryo mortality to be significantly delayed by several weeks in
      diapausing embryos irradiated and allowed to recover in the dark. These atypical
      responses to UV-R induced DNA damage may be due to the unique annual killifish
      life history and provide insight into DNA damage repair and recognition
      mechanisms during embryonic dormancy.

PMID- 25387430
TI  - Meta-analysis of Ubiquilin1 gene polymorphism and Alzheimer's disease risk.
AB  - BACKGROUND: Some studies have evaluated the association between the Ubiquilin 1
      (UBQLN1) gene UBQ-8i polymorphism and Alzheimer's disease (AD). However, the
      results remain uncertain. We carried out a meta-analysis to derive a more
      comprehensive estimation of this association. MATERIAL/METHODS: Case-control
      studies were identified by searching databases of PubMed, EMBASE, Web of Science,
      CNKI, CBM, Wanfang, and VIP. Odds ratios (ORs) with 95% confidence intervals
      (CIs) were used to assess the strength of the association. RESULTS: The UBQ-8i
      polymorphism was significantly associated with an increased AD risk (OR=1.15;
      95%CI 1.05-1.25; P=0.002). The combination of adjusted ORs also found UBQ-8i
      polymorphism was significantly associated with AD risk (OR=1.15; 95%CI 1.02-1.30;
      P=0.02). When stratified by APOE epsilon4 status, both APOE epsilon4 carriers and
      APOE non-epsilon4 carriers with UBQ-8i polymorphism had significantly increased
      AD risk (OR=1.28; 95%CI 1.05-1.56; P=0.01 and OR=1.25; 95%CI 1.04-1.50; P=0.02).
      In the subgroup analysis according to age, UBQ-8i polymorphism was significantly
      associated with LOAD risk (OR=1.17; 95%CI 1.05-1.31; P=0.005), but not with EOAD
      risk (OR=1.12; 95%CI 0.95-1.31; P=0.17). CONCLUSIONS: These results suggest that
      the UBQ-8i polymorphism is associated with AD risk.

PMID- 25387431
TI  - Retrospective and comparative study of inflammatory myofibroblastic tumor of the
      liver.
AB  - BACKGROUND AND AIM: Inflammatory myofibroblastic tumor of the liver (IMTL) is a
      very rare benign disease with a good prognosis. The study aims to determine the
      clinical, radiological, and pathological characteristics of IMTL. The diagnosis
      and treatment strategies were discussed. METHODS: A total of 11 patients with
      pathologically confirmed IMTL receiving treatment over a 15-year period were
      reviewed retrospectively. The analysis included demographics information and
      pertinent clinical data. Results obtained from patients with hepatocellular
      carcinoma (HCC), intrahepatic cholangiocarcinoma (IHCC), and metastatic liver
      cancer (MLC) receiving surgical resection were compared. RESULTS: In comparison
      to HCC, IHCC, and MLC, IMTL has an earlier onset (P < 0.001). IMTL patients had
      significantly lower aspartate aminotransferase (P = 0.003) and higher alkaline
      phosphatase (P = 0.034) than HCC patients, and higher gamma-glutamyl
      transpeptidase (P = 0.010) than MLC patients. Increased serum alpha-fetoprotein
      level was detected in only one patient. Serum alpha-fetoprotein was significantly
      lower in patients with IMTL (P = 0.000) than in those with HCC but not IHCC (P =
      0.558) or MLC (P = 0.514). In contrast to elevated serum CA19-9 in patients with
      HCC/IHCC/MLC, the serum CA19-9 in IMTL cases was generally normal (vs HCC P =
      0.008; vs IHCC P = 0.000; vs MLC P = 0.022). In nine IMTL patients, the tumor
      appeared as a hypoechogenic solid mass on the ultrasonography. In contrast, most
      patients with HCC, IHCC, or MLC showed hybrid echo. In contrast computed
      tomography and magnetic resonance imaging, the lesion of IMTL and MLC appeared as
      peripheral enhancement. CONCLUSION: Lab tests, imaging features, and patient
      history are helpful in the differential diagnosis of IMTL from HCC/IHCC/MLC.
      Surgical resection is curative for IMTL.

PMID- 25387432
TI  - Retinal-binding proteins mirror prokaryotic dynamics in multipond solar salterns.
AB  - Microbial opsin (i.e. retinal-binding protein) dynamics has been studied along a
      salinity gradient in Santa Pola solar salterns (Alicante, Spain) by using culture
      independent approaches and statistical analyses. Five ponds of salinities ranging
      from 18% to above 40% were sampled nine times along a year. Forty-three opsin
      like sequences were retrieved by denaturing gradient gel electrophoresis and
      clustered into 18 different phylogroups, indicating that their diversity was
      higher than expected according to previous data. Moreover, the statistical
      correlation between environmental factors controlling microbial community
      structure and dynamics of environmental rhodopsin proteins indicated almost
      identical temporal fluctuations between the opsin-related sequences and their
      corresponding putative 'producers' in nature. Although most sequences were
      related to others previously detected in hypersaline environments, some pond
      specific opsins putatively belonged to previously uncharacterized hosts.
      Furthermore, we propose that subtle changes in the bacteriorhodopsin 'retinal
      proton binding pocket', which is key in the photocycle function, could be the
      molecular basis behind a fine 'photocycle-tuning' mechanism to avoid
      inter/intraspecies light-competition in hypersaline environments. 

PMID- 25387433
TI  - Insulin pump use and glycemic control in adolescents with type 1 diabetes:
      Predictors of change in method of insulin delivery across two years.
AB  - Few studies have explored durability of insulin pump use, and none have explored
      the link between depression and pump discontinuation. To examine the relationship
      between depressive symptoms [measured by the Children's Depression Inventory
      (CDI)], method of insulin delivery, and hemoglobin A1c (A1c), mixed models were
      used with data from 150 adolescents with type 1 diabetes (T1D) and visits every 6
      months for 2 years. Of the 63% who used a pump, compared with multiple daily
      injections (MDI) at baseline, there were higher proportions who were non
      minorities, had caregivers with a college degree, private insurance, and two
      caregivers in the home (p <= 0.01). After adjusting for time, sex, age, T1D
      duration, frequency of blood glucose monitoring, ethnicity, insurance, and
      caregiver number and education, baseline pump use was associated with -0.79%
      lower mean A1c [95% confidence interval (CI): -1.48, -0.096; p = 0.03]. For those
      using a pump at baseline, but switching to MDI during the study (n = 9), mean A1c
      was 1.38% higher (95% CI: 0.68, 2.08; p < 0.001) than that for those who did not
      switch method of delivery. A 10-point increase in CDI was associated with a 0.39%
      increase in A1c (95% CI: 0.16, 0.61; p = 0.001), independent of pump use.
      Regarding the temporal relationship between CDI score and changing method of
      insulin delivery, prior higher CDI score was associated with switching from pump
      to MDI (odds ratio = 1.21; 95% CI: 1.05, 1.39; p = 0.007). Clinicians should be
      aware of the associations between depressive symptoms, change in insulin delivery
      method, and the effect on glycemic control. 

PMID- 25387434
TI  - Master apical file size - smaller or larger: a systematic review of microbial
      reduction.
AB  - The purpose of this systematic review was to determine, in patients undergoing
      root canal treatment, whether apical enlargement of canals affected microbial
      reduction. A PICO (population, intervention, comparison and outcome) strategy was
      developed to identify previously published studies dealing with apical size of
      canal and microbial reduction. The MEDLINE, Embase, Cochrane and PubMed databases
      were searched. Additionally, the bibliographies of all relevant articles and
      textbooks were manually searched. Based on inclusion and exclusion criteria, two
      reviewers independently selected the relevant articles. Due to the variety of
      methodologies and different techniques used to measure outcome for master apical
      file enlargement, it was not possible to standardize the research data and to
      apply a meta-analysis. Seven articles were identified that met the inclusion
      criteria. Five of the seven articles generally concluded that canal enlargement
      reduced bioburden in the root canal system. Two articles reported no difference
      in canals enlarged to size 25 or 40. The results of the systematic review
      confirmed that more evidence-based research in this area is needed. With the
      limited information currently available, the best current available clinical
      evidence suggests that contemporary chemomechanical debridement techniques with
      canal enlargement techniques do not eliminate bacteria during root canal
      treatment at any size. 

PMID- 25387435
TI  - Towards a systemic paradigm in carcinogenesis: linking epigenetics and genetics.
AB  - For at least 30 years cancer has been defined as a genetic disease and explained
      by the so-called somatic mutation theory (SMT), which has dominated the
      carcinogenesis field. Criticism of the SMT has recently greatly increased,
      although still not enough to force all SMT supporters to recognize its limits.
      Various researchers point out that cancer appears to be a complex process
      concerning a whole tissue; and that genomic mutations, although variably
      deleterious and unpredictably important in determining the establishment of the
      neoplastic phenotype, are not the primary origin for a malignant neoplasia. We
      attempt to describe the inadequacies of the SMT and demonstrate that epigenetics
      is a more logical cause of carcinogenesis. Many previous models of carcinogenesis
      fall into two classes: (i) in which some biological changes inside cells alone
      lead to malignancy; and (ii) requiring changes in stroma/extracellular matrix. We
      try to make clear that in the (ii) model genomic instability is induced by
      persistent signals coming from the microenvironment, provoking epigenetic and
      genetic modifications in tissue stem cells that can lead to cancer. In this
      perspective, stochastic mutations of DNA are a critical by-product rather then
      the primary cause of cancer. Indirect support for such model of carcinogenesis
      comes from the in vitro and vivo experiments showing apparent 'reversion' of
      cancer phenotypes obtained via physiological factors of cellular differentiation
      (cytokines and other signaling molecules) or drugs, even if the key mutations are
      not 'reversed'. 

PMID- 25387436
TI  - Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview.
AB  - The FTO (fat mass and obesity-associated) gene has a strong linkage
      disequilibrium block, within which SNPs have been identified that are involved in
      the development of obesity. Recently some of these variants have also been
      associated with cancer. However, identification of the possible mechanisms that
      could explain these associations has proven to be elusive. It has been found that
      FTO polymorphisms can regulate the expression of genes at large kilobases of
      distance as well as the expression of the FTO gene itself, and regions for
      transcription factor binding. To date it has been observed that variants
      rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995
      and rs1121980 are associated with the risk of developing cancer. Some studies
      have produced negative results when comparing the same polymorphisms, but make a
      simple association between polymorphic variants and cancer, have proved difficult
      because this relation is by nature multifactorial. A certain degree of variation
      resulting from the improper design of studies or processing of data can lead to
      erroneous conclusions. However, it is now unquestionable that certain FTO
      polymorphisms regulate genetic expression related to cancer susceptibility,
      although this field is just beginning to be understood. 

PMID- 25387437
TI  - Health literacy and the digital divide among older Americans.
AB  - BACKGROUND: Among the requirements for meaningful use of electronic medical
      records (EMRs) is that patients must be able to interact online with information
      from their records. However, many older Americans may be unprepared to do this,
      particularly those with low levels of health literacy. OBJECTIVE: The purpose of
      the study was to quantify the relationship between health literacy and use of the
      Internet for obtaining health information among Americans aged 65 and older.
      DESIGN: We performed retrospective analysis of 2009 and 2010 data from the Health
      and Retirement Study, a longitudinal survey of a nationally representative sample
      of older Americans. PARTICIPANTS: Subjects were community-dwelling adults aged 65
      years and older (824 individuals in the general population and 1,584 Internet
      users). MAIN MEASURES: Our analysis included measures of regular use of the
      Internet for any purpose and use of the Internet to obtain health or medical
      information; health literacy was measured using the Rapid Estimate of Adult
      Literacy in Medicine-Revised (REALM-R) and self-reported confidence filling out
      medical forms. KEY RESULTS: Only 9.7% of elderly individuals with low health
      literacy used the Internet to obtain health information, compared with 31.9% of
      those with adequate health literacy. This gradient persisted after controlling
      for sociodemographic characteristics, health status, and general cognitive
      ability. The gradient arose both because individuals with low health literacy
      were less likely to use the Internet at all (OR = 0.36 [95% CI 0.24 to 0.54]) and
      because, among those who did use the Internet, individuals with low health
      literacy were less likely to use it to get health or medical information (OR =
      0.60 [95% CI 0.47 to 0.77]). CONCLUSION: Low health literacy is associated with
      significantly less use of the Internet for health information among Americans
      aged 65 and older. Web-based health interventions targeting older adults must
      address barriers to substantive use by individuals with low health literacy, or
      risk exacerbating the digital divide.

PMID- 25387438
TI  - Pocket-sized ultrasound as an aid to physical diagnosis for internal medicine
      residents: a randomized trial.
AB  - BACKGROUND: Proficiency and self-confidence in the physical examination is poor
      among internal medicine residents and interest in ultrasound technology has
      expanded. OBJECTIVE: We aimed to determine whether a pocket-sized ultrasound
      improves the diagnostic accuracy and confidence of residents after a 3-h training
      session and 1 month of independent practice. DESIGN: This was a randomized
      parallel group controlled trial. PARTICIPANTS: Forty internal medicine residents
      in a single program at an academic medical center participated in the study.
      INTERVENTION: Three hours of training on use of pocket-sized ultrasound was
      followed by 1 month of independent practice. MAIN MEASURES: The primary outcome
      was a comparison of the diagnostic accuracy of a physical exam alone versus a
      physical examination augmented with a pocket-sized ultrasound. Other outcomes
      included confidence in exam findings and a survey of attitudes towards the
      physical exam and the role of ultrasound. KEY RESULTS: Residents in the
      intervention group using a pocket-sized ultrasound correctly identified an
      average of 7.6 of the 17 abnormal findings (accuracy rate of 44.9 %). Those in
      the control group correctly identified an average of 6.4 abnormal findings
      (accuracy rate of 37.6 %, p = 0.11). Residents in the intervention group
      identified on average 15.9 findings as abnormal when no abnormality existed
      (false positive rate of 16.8 %). Those in the control group incorrectly
      identified an average of 15.5 positive findings (false positive rate of 16.3 %).
      There was no difference between groups regarding self-assessed confidence in
      physical examination. Residents in the intervention group identified 6.1 of 13
      abnormal cardiac findings versus the control group's 4.5 of 13, an accuracy rate
      of 47.0 % versus 34.6 % (p = 0.023). CONCLUSIONS: The diagnostic ability of
      internal medicine residents did not significantly improve with use of a pocket
      sized ultrasound device after a 3-h training session and 1 month of independent
      practice. TRIAL REGISTRATION: clinicaltrials.gov: number NCT01948076; URL
      http://clinicaltrials.gov/ct2/show/study/NCT01948076?term=ultrasound+physical+exa
      &rank=2.

PMID- 25387439
TI  - Why do people avoid medical care? A qualitative study using national data.
AB  - BACKGROUND: Many studies have examined barriers to health care utilization, with
      the majority conducted in the context of specific populations and diseases. Less
      research has focused on why people avoid seeking medical care, even when they
      suspect they should go. OBJECTIVE: The purpose of the study was to present a
      comprehensive description and conceptual categorization of reasons people avoid
      medical care. DESIGN: Data were collected as part of the 2008 Health Information
      National Trends Survey, a cross-sectional national survey. PARTICIPANTS:
      Participant-generated reasons for avoiding medical care were provided by 1,369
      participants (40% male; M age =48.9; 75.1% non-Hispanic white, 7.4% non-Hispanic
      black, 8.5% Hispanic or Latino/a). MAIN MEASURES: Participants first indicated
      their level of agreement with three specific reasons for avoiding medical care;
      these data are reported elsewhere. We report responses to a follow-up question in
      which participants identified other reasons they avoid seeking medical care.
      Reasons were coded using a general inductive approach. KEY RESULTS: Three main
      categories of reasons for avoiding medical care were identified. First, over one
      third of participants (33.3% of 1,369) reported unfavorable evaluations of
      seeking medical care, such as factors related to physicians, health care
      organizations, and affective concerns. Second, a subset of participants reported
      low perceived need to seek medical care (12.2%), often because they expected
      their illness or symptoms to improve over time (4.0%). Third, many participants
      reported traditional barriers to medical care (58.4%), such as high cost (24.1%),
      no health insurance (8.3%), and time constraints (15.6%). We developed a
      conceptual model of medical care avoidance based on these results. CONCLUSIONS:
      Reasons for avoiding medical care were nuanced and highly varied. Understanding
      why people do not make it through the clinic door is critical to extending the
      reach and effectiveness of patient care, and these data point to new directions
      for research and strategies to reduce avoidance.

PMID- 25387440
TI  - Capsule commentary on Turner et al., chronic opioid therapy urine drug testing in
      primary care: prevalence and predictors of aberrant results.

PMID- 25387441
TI  - Capsule commentary on Gerber et al., hormone therapy use in women veterans
      accessing veterans health administration care: a national cross-sectional study.

PMID- 25387442
TI  - Capsule commentary on Stevens et al., primary care medical home experience and
      health-related quality of life among adult Medicaid patients with type 2
      diabetes.

PMID- 25387443
TI  - Pharmacotherapeutic management of metastatic, castration-resistant prostate
      cancer in the elderly: focus on non-chemotherapy agents.
AB  - In the past 4 years, five new agents have been approved for metastatic,
      castration-resistant prostate cancer. Four of them are non-chemotherapeutic and
      generally well tolerated. However, each has toxicities that can negatively impact
      patients, particularly the elderly. This review covers the epidemiology of
      prostate cancer in elderly men. It discusses the efficacy data for sipuleucel-T,
      abiraterone in chemotherapy-naive patients, enzalutamide in chemotherapy-naive
      patients and radium-223 and presents any additional studies done for those over
      75 years of age. Disease burden, such as the presence or absence of visceral
      disease, and comorbid conditions weigh into the selection of therapy and are
      discussed here. Drug-drug interactions between these agents and other drugs
      commonly used in the elderly population are also considered. The emerging
      therapies tasquinimod and ipilimumab are reviewed. With the arrival of so many
      agents for prostate cancer, selection of the most appropriate agent can be
      perplexing, particularly because these agents were tested against placebo, not
      one another. Furthermore, the study population differs significantly from those
      seen in clinical practice. This review addresses these issues. 

PMID- 25387444
TI  - Migraine and risk of hemorrhagic stroke: a study based on data from general
      practice.
AB  - BACKGROUND: We investigated the association between hemorrhagic stroke and
      migraine using data from The Health Improvement Network database. FINDINGS: We
      ascertained 1,797 incident cases of intracerebral hemorrhage (ICH) and 1,340 of
      subarachnoid hemorrhage (SAH). Density-based sampling was used to select 10,000
      controls free from hemorrhagic stroke. Using unconditional logistic regression
      models, we calculated the risk of hemorrhagic stroke associated with migraine,
      adjusting for age, sex, calendar year, alcohol, body mass index, hypertension,
      previous cerebrovascular disease, oral contraceptive use, and health services
      utilization.The risk (odds ratio [OR]) of ICH among migraineurs was 1.2 (95%
      confidence interval [CI] 0.9-1.5), and of SAH was (1.2, 95% CI 0.9-1.5). The
      association with ICH was stronger for migraine diagnosed >=20 years prior to ICH
      (OR 1.6, 95% CI 1.0-2.4), but not with SAH (OR 1.1, 95% CI 0.6-2.1). In analyses
      stratified by migraine type and gender, the OR of ICH in women with migraine with
      aura was 1.7 (95% CI 0.9-3.4) and the corresponding OR of SAH in women was 1.2
      (95% CI 0.6-2.3). CONCLUSION: No clear increased risk of ICH or SAH was observed
      in migraineurs.

PMID- 25387445
TI  - Novel multiferroicity in GdMnO3 thin films with self-assembled nano-twinned
      domains.
AB  - There have been many interests in exploring multiferroic materials with superior
      ferroelectric and magnetic properties for the purpose of developing
      multifunctional devices. Fabrication of thin films plays an important role in
      achieving this purpose, since the multiferroicity can be tuned via strain,
      dimensionality, and size effect, without varying the chemical composition. Here,
      we report exotic multiferroic behaviors, including high-TC (~75 K) ferroelectric
      state, a large spontaneous polarization (~4900 MUC/m(2)) and relatively strong
      ferromagnetism emerging at ~105 K, in orthorhombic GdMnO3/SrTiO3 (001) thin films
      with self-assembled nano-scale twin-like domains. We propose a possible ab-plane
      spiral-spin-order phase to be responsible for the large spontaneous polarization
      in the films, which can only be stabilized by relatively high magnetic field H >
      6 T in the bulk crystals. It is suggested that the nano-scale twin-like domain
      structure is essential for the high temperature ferroelectricity and
      ferromagnetism of the thin films.

PMID- 25387446
TI  - Pre-treatment by omalizumab allows allergen immunotherapy in children and young
      adults with severe allergic asthma.

PMID- 25387447
TI  - Are e-cigarettes effective in smoking cessation?

PMID- 25387448
TI  - Cerebral Networks Linked to Itch-related Sensations Induced by Histamine and
      Capsaicin.
AB  - This functional magnetic resonance imaging (fMRI) study explored the central
      nervous processing of itch induced by histamine and capsaicin, delivered via
      inactivated cowhage spicules, and the influence of low-dose naltrexone. Scratch
      bouts were delivered at regular intervals after spicule insertion in order
      temporarily to suppress the itch. At the end of each trial the subjects rated
      their itch and scratch-related sensations. Stepwise multiple regression analyses
      were employed for identifying cerebral networks contributing to the intensities
      of "itching", "burning", "stinging", "pricking" and "itch relief by scratching".
      In the capsaicin experiments a network for "burning" was identified, which
      included the posterior insula, caudate and putamen. In the histamine experiments
      networks for "itching" and "itch relief" were found, which included operculum,
      hippocampus and amygdala. Naltrexone generally reduced fMRI activation and the
      correlations between fMRI signal and ratings. Furthermore, scratching was
      significantly less pleasant under naltrexone.

PMID- 25387449
TI  - Translating evidence into practice.

PMID- 25387450
TI  - Characteristics and TB treatment outcomes in TB patients with viral hepatitis,
      New York City, 2000-2010.
AB  - Literature surrounding the burden of and factors associated with hepatitis B
      virus (HBV) and hepatitis C virus (HCV) infection in persons with tuberculosis
      (TB) disease remains limited and focused on populations outside the USA. Cross
      matched New York City (NYC) TB and viral hepatitis surveillance data were used to
      estimate the proportion of NYC adults diagnosed with TB from 2000 to 2010 with a
      report of viral hepatitis infection and to describe the impact of viral hepatitis
      infection on TB treatment completion and death. For 9512 TB patients, HCV
      infection was reported in 4.2% and HBV infection in 3.7%; <1% of TB patients had
      both HCV and HBV infection. The proportion of TB patients with HCV infection to
      die before TB treatment completion was larger than in TB patients without a viral
      hepatitis report (21% vs. 9%); this association remained when stratified by HIV
      status. There was no significant difference in death before treatment completion
      for TB patients with HBV infection compared to TB patients without a viral
      hepatitis report when stratified by HIV status. These findings reinforce the
      importance of hepatitis testing and providing additional support to TB patients
      with viral hepatitis infection.

PMID- 25387451
TI  - Hyperglycemia and chronic liver diseases on risk of hepatocellular carcinoma in
      Chinese patients with type 2 diabetes--National cohort of Taiwan Diabetes Study.
AB  - This study examined whether glycated hemoglobin A1C (HbA1C) and chronic liver
      diseases are associated with hepatocellular carcinoma (HCC) risk in Type 2
      diabetic patients. A retrospective cohort study consisting of 51,705 patients
      with Type 2 diabetes aged 30 and over enrolled in the National Diabetes Care
      Management Program before 2004 was used in Cox proportional hazards models. HbA1C
      was independently associated with HCC incidence, and multivariate-adjusted hazard
      ratio (HR) of HCC was 1.20 (95% confidence interval, CI: 1.02-1.41) for patients
      with a level of HbA1c >= 9% compared with patients with a level of HbA1c <7%
      after multivariate adjustment. We observed a significant linear trend in HCC
      incidence with increasing HbA1c (p for trend = 0.02, HR = 1.07, 95% CI = 1.01
      1.12 for every 1% increment in HbA1c). We observed significant HRs of HCC for
      patients with a level of HbA1c >= 9% with alcoholic liver damage, liver
      cirrhosis, HBV, HCV and any one of chronic liver diseases compared with patients
      with a level of HbA1c <9% and no counterpart comorbidity in the entire sample (HR
      = 8.63, 95% CI = 1.41-52.68; HR = 5.02, 95% CI = 3.10-8.12; HR = 2.53, 95% CI =
      1.10-5.85; HR = 1.79, 95% CI = 1.01-3.17; and HR = 3.59, 95% CI = 2.56-5.02,
      respectively). Our results suggest significant joint associations of HbA1c >= 9%
      and chronic liver diseases. Lifestyle or treatment interventions such as
      maintaining a satisfactory glycemic control and chronic liver diseases may reduce
      the burden of HCC.

PMID- 25387452
TI  - Kinetic buffers.
AB  - This paper proposes a new type of molecular device that is able to act as an
      inverse proton sponge to slowly decrease the pH inside a reaction vessel. This
      makes the automatic monitoring of the concentration of pH-sensitive systems
      possible. The device is a composite formed of an alkyl chloride, which
      kinetically produces acidity, and a buffer that thermodynamically modulates the
      variation in pH value. Profiles of pH versus time (pH-t plots) have been
      generated under various experimental conditions by computer simulation, and the
      device has been tested by carrying out automatic spectrophotometric titrations,
      without using an autoburette. To underline the wide variety of possible
      applications, this new system has been used to realize and monitor HCl uptake by
      a di-copper(II) bistren complex in a single run, in a completely automatic
      experiment. 

PMID- 25387453
TI  - Dose response biology of resveratrol in obesity.
AB  - Obesity is a major health problem throughout the world, and it is increasing both
      in prevalence and severity. Pharmaceutical approaches developed for the treatment
      of obesity, despite short-term benefits, often are associated with rebound weight
      gain after the cessation of drug use and serious side effects deriving from the
      medication can occur. Resveratrol has been well recognized as an anti-obesity
      substance for its lipid-lowering function as well as calorie-restriction effect.
      This polyphenol induces hormetic dose responses in a wide range of biological
      models, affecting numerous endpoints of biomedical and therapeutic significance.
      From an hormetic standpoint, we will discuss the potential relevance of
      resveratrol in the management of obesity and related comorbid conditions,
      emphasizing its ability to control simultaneously various pathological mechanisms
      associated with obesity. 

PMID- 25387455
TI  - Vegetative regeneration capacities of five ornamental plant invaders after
      shredding.
AB  - Vegetation management often involves shredding to dispose of cut plant material
      or to destroy the vegetation itself. In the case of invasive plants, this can
      represent an environmental risk if the shredded material exhibits vegetative
      regeneration capacities. We tested the effect of shredding on aboveground and
      below-ground vegetative material of five ornamental widespread invaders in
      Western Europe that are likely to be managed by cutting and shredding techniques:
      Buddleja davidii (butterfly bush, Scrophulariaceae), Fallopia japonica (Japanese
      knotweed, Polygonaceae), Spiraea * billardii Herincq (Billard's bridewort,
      Rosaceae), Solidago gigantea (giant goldenrod, Asteraceae), and Rhus typhina L.
      (staghorn sumac, Anacardiaceae). We looked at signs of vegetative regeneration
      and biomass production, and analyzed the data with respect to the season of plant
      cutting (spring vs summer), the type of plant material (aboveground vs below
      ground), and the shredding treatment (shredded vs control). All species were
      capable of vegetative regeneration, especially the below-ground material. We
      found differences among species, but the regeneration potential was generally
      still present after shredding despite a reduction of growth rates. Although it
      should not be excluded in all cases (e.g., destruction of giant goldenrod and
      staghorn sumac aboveground material), the use of a shredder to destroy woody
      alien plant material cannot be considered as a general management option without
      significant environmental risk.

PMID- 25387454
TI  - Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue
      engineering.
AB  - There is an unmet need for a consistent set of tools for the evaluation of 3D
      printed constructs. A toolbox developed to design, characterize, and evaluate 3D
      printed poly(propylene fumarate) scaffolds is proposed for vascularized
      engineered tissues. This toolbox combines modular design and non-destructive
      fabricated design evaluation, evaluates biocompatibility and mechanical
      properties, and models angiogenesis. 

PMID- 25387456
TI  - A biological condition gradient model for historical assessment of estuarine
      habitat structure.
AB  - Coastal ecosystems are affected by ever-increasing natural and human pressures.
      Because the physical, chemical, and biological characteristics unique to
      estuarine ecosystems control the ways that biological resources respond to
      ecosystem stressors, we present a flexible and adaptable biological assessment
      method for estuaries. The biological condition gradient (BCG) is a scientific
      framework of biological response to increasing anthropogenic stress that is
      comprehensive and ecosystem based and evaluates environmental conditions and the
      status of ecosystem services in order to identify, communicate, and prioritize
      management action. Using existing data, we constructed the first estuarine BCG
      framework that examines changes in habitat structure through time. Working in a
      New England (U.S.) estuary with a long history of human influence, we developed
      an approach to define a reference level, which we described as a "minimally
      disturbed" range of conditions for the ecosystem, anchored by observations before
      1850 AD. Like many estuaries in the U.S., the relative importance of
      environmental stressors changed over time, but even qualitative descriptions of
      the biological indicators' status provided useful information for defining
      condition levels. This BCG demonstrated that stressors rarely acted alone and
      that declines in one biological indicator influenced the declines of others. By
      documenting the biological responses to cumulative stressors, the BCG inherently
      suggests an ecosystem-based approach to management. Additionally, the BCG process
      initiates thinking over long time scales and can be used to inspire scientists,
      managers, and the public toward environmental action. 

PMID- 25387458
TI  - First epidemiological report of feline heartworm infection in the Barcelona
      metropolitan area (Spain).
AB  - BACKGROUND: The metropolitan area of Barcelona is the most densely populated
      metropolitan area on the Mediterranean coast. Several studies have reported the
      presence of canine heartworm disease in this region; however, there are no
      published epidemiological data regarding feline heartworm in this region and the
      prevalence in this species remains unknown. METHODS: Serum samples from 758 cats
      living in the metropolitan area of Barcelona (Spain) were collected between 2012
      and 2013. To establish the seroprevalence of heartworm infection in cats,
      serological techniques for anti-D.immitis and anti-Wolbachia antibody detection
      were used while a commercial ELISA test kit was used to detect circulating
      D.immitis antigens. RESULTS: Of these samples, 11.47% were positive to D.immitis
      and Wolbachia surface protein antibodies and 0.26% were positive to D.immitis
      antigens. The higher antibody seroprevalences were found in the areas that follow
      the courses of the rivers Llobregat and Anoia (Baix Llobregat 11.5%, Valles
      Occidental 13.2%; Barcelones 11.7%) where humidity and vegetation favour the
      development of the mosquito vectors. High antibody seroprevalences were also
      found in the urban areas (Barcelona city 13.1%; Sabadell 15.5%), which
      demonstrates that city cats are also at risk from D.immitis infection.
      CONCLUSIONS: Generally, in Spain cats do not receive prophylactic treatment and
      therefore the risk of infection is higher in this species than in dogs. Adequate
      prophylactic plans should be implemented in the feline population. This is the
      first epidemiologic study on feline heartworm infection to be carried out in
      continental Spain.

PMID- 25387459
TI  - The blood pressure response to exercise in youth with impaired glucose tolerance
      and type 2 diabetes.
AB  - Type 2 diabetes is associated with hypertension and an increased risk of
      cardiovascular disease. In adults, blood pressure (BP) responses to exercise are
      predictive of these complications. To determine if the hemodynamic response to
      exercise is exaggerated in youth with dysglycemia (DG) compared with
      normoglycemic overweight/ obese (OB) and healthy weight (HW) controls a cross
      sectional comparison of BP and heart rate (HR) responses to graded exercise to
      exhaustion in participants was performed. DG and OB youth were matched for age,
      BMI z-score, height and sex. Systolic (SBP) and diastolic BP (DBP) were measured
      every 2 min, and HR was measured every 1 min. SBP was higher in OB and DG
      compared with HW youth at rest (p < .001). Despite working at lower relative
      workloads compared with HW, the BP response was elevated during exercise in OB
      and DG. For similar HR and oxygen consumption rates, BP responses to exercise
      were slightly higher in OB and DG compared with HW. OB and DG youth both display
      elevated resting and exercise BP relative to HW peers. Obesity may play a greater
      role than dysglycemia in the exaggerated BP response to exercise in youth. 

PMID- 25387461
TI  - Monte Carlo simulations of nanoscale focused neon ion beam sputtering of copper:
      elucidating resolution limits and sub-surface damage.
AB  - A three dimensional Monte Carlo simulation program was developed to model
      physical sputtering and to emulate vias nanomachined by the gas field ion
      microscope. Experimental and simulation results of focused neon ion beam induced
      sputtering of copper are presented and compared to previously published
      experiments. The simulation elucidates the nanostructure evolution during the
      physical sputtering of high aspect ratio nanoscale features. Quantitative
      information such as the energy-dependent sputtering yields, dose dependent aspect
      ratios, and resolution-limiting effects are discussed. Furthermore, the nuclear
      energy loss and implant concentration beneath the etch front is correlated with
      the sub-surface damage revealed by transmission electron microscopy at different
      beam energies. 

PMID- 25387460
TI  - Reagent and laboratory contamination can critically impact sequence-based
      microbiome analyses.
AB  - BACKGROUND: The study of microbial communities has been revolutionised in recent
      years by the widespread adoption of culture independent analytical techniques
      such as 16S rRNA gene sequencing and metagenomics. One potential confounder of
      these sequence-based approaches is the presence of contamination in DNA
      extraction kits and other laboratory reagents. RESULTS: In this study we
      demonstrate that contaminating DNA is ubiquitous in commonly used DNA extraction
      kits and other laboratory reagents, varies greatly in composition between
      different kits and kit batches, and that this contamination critically impacts
      results obtained from samples containing a low microbial biomass. Contamination
      impacts both PCR-based 16S rRNA gene surveys and shotgun metagenomics. We provide
      an extensive list of potential contaminating genera, and guidelines on how to
      mitigate the effects of contamination. CONCLUSIONS: These results suggest that
      caution should be advised when applying sequence-based techniques to the study of
      microbiota present in low biomass environments. Concurrent sequencing of negative
      control samples is strongly advised.

PMID- 25387462
TI  - Six cases of (severe) hypoglycaemia associated with gabapentin use in both
      diabetic and non-diabetic patients.

PMID- 25387463
TI  - Asymmetric Pectus Excavatum Is Associated with Overgrowth of Ribs Rather Than
      Cartilage.
AB  - BACKGROUND: To evaluate whether the overgrowth of costal cartilage exists in
      patients with pectus excavatum, we compared the length of the costal cartilage
      and ribs between patients with asymmetric pectus excavatum and controls without
      chest wall deformity using three-dimensional computed tomography. MATERIALS AND
      METHODS: Nineteen adult patients with asymmetric pectus excavatum and 19 age and
      sex matched controls without chest wall deformity were enrolled. We measured the
      full lengths of the fourth to sixth ribs and costal cartilage using three
      dimensional volume-rendered computed tomography images and curved multiplanar
      reformatting techniques. The lengths of ribs and costal cartilage, their
      summations, and the costal index ([length of cartilage/length of rib] * 100 [%])
      were compared on the asymmetrically depressed side of patients (Group A), the
      opposite side of the same patients (Group B), and controls (Group C) at the
      fourth to sixth levels. RESULTS: The lengths of the ribs of groups A and B were
      significantly longer (p < 0.001) than those of group C (299.4 +/- 14.9 mm vs.
      302.9 +/- 15.3 mm vs. 288.9 +/- 12.2 at the fourth level, 312.3 +/- 14.1 mm vs.
      318.4 +/- 14.6 mm vs. 303.2 +/- 12.7 mm at the fifth level, and 322.2 +/- 17.2 mm
      vs. 325.2 +/- 17.5 mm vs. 309.4 +/- 12.3 mm at the sixth level). The costal
      cartilage lengths did not differ (p > 0.05) among the three groups (53.1 +/- 7.3
      mm vs. 54.6 +/- 8.6 mm vs. 52.9 +/- 5.2 at the fourth level, 71.9 +/- 9.6 mm vs.
      72.3 +/- 9.9 mm vs. 69.2 +/- 7.1 mm at the fifth level, and 100.1 +/- 15.2 mm vs.
      104.2 +/- 15.8 mm vs. 99.1 +/- 9.1 mm at sixth level). The summations of the rib
      and costal cartilage lengths were longer in groups A and B than in group C. The
      costal indices were not different among the three groups at the fourth, fifth,
      and sixth rib levels. CONCLUSION: In patients who had asymmetric pectus excavatum
      with a >= 21-degree angle of sternal rotations, the ribs but not the costal
      cartilage were longer than those of controls. These findings suggest that
      cartilage overgrowth is not the main factor responsible for asymmetric pectus
      excavatum, and it could instead be related to abnormal rib growth.

PMID- 25387464
TI  - Planning for Better Care Fund was a "shambles," says parliamentary committee.

PMID- 25387466
TI  - South American guidelines for cardiovascular disease prevention and
      rehabilitation.

PMID- 25387465
TI  - Contrasting modes and tempos of venom expression evolution in two snake species.
AB  - Selection is predicted to drive diversification within species and lead to local
      adaptation, but understanding the mechanistic details underlying this process and
      thus the genetic basis of adaptive evolution requires the mapping of genotype to
      phenotype. Venom is complex and involves many genes, but the specialization of
      the venom gland toward toxin production allows specific transcripts to be
      correlated with specific toxic proteins, establishing a direct link from genotype
      to phenotype. To determine the extent of expression variation and identify the
      processes driving patterns of phenotypic diversity, we constructed genotype
      phenotype maps and compared range-wide toxin-protein expression variation for two
      species of snake with nearly identical ranges: the eastern diamondback
      rattlesnake (Crotalus adamanteus) and the eastern coral snake (Micrurus fulvius).
      We detected significant expression variation in C. adamanteus, identified the
      specific loci associated with population differentiation, and found that loci
      expressed at all levels contributed to this divergence. Contrary to expectations,
      we found no expression variation in M. fulvius, suggesting that M. fulvius
      populations are not locally adapted. Our results not only linked expression
      variation at specific loci to divergence in a polygenic, complex trait but also
      have extensive conservation and biomedical implications. C. adamanteus is
      currently a candidate for federal listing under the Endangered Species Act, and
      the loss of any major population would result in the irrevocable loss of a unique
      venom phenotype. The lack of variation in M. fulvius has significant biomedical
      application because our data will assist in the development of effective
      antivenom for this species. 

PMID- 25387467
TI  - Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance
      via interference with the DNA damage response.
AB  - Host responses to systemic anti-cancer treatment play important roles in the
      development of anti-cancer drug resistance. Here we show that F4/80(+)/CD11b(low)
      splenocytes mediate the resistance to DNA-damaging chemotherapeutics induced by
      two platinum-induced fatty acids (PIFAs), 12-S-keto-5,8,10-heptadecatrienoic acid
      and 4,7,10,13-hexadecatetraenoic acid (16:4(n-3)) in xenograft mouse models.
      Splenectomy or depletion of splenic macrophages by liposomal clodronate protects
      against PIFA-induced chemoresistance. In addition, we find that 12-S-HHT, but not
      16:4(n-3), functions via leukotriene B4 receptor 2 (BLT2). Genetic loss or
      chemical inhibition of BLT2 prevents 12-S-HHT-mediated resistance. Mass
      spectrometry analysis of conditioned medium derived from PIFA-stimulated splenic
      macrophages identifies several lysophosphatidylcholines as the resistance
      inducing molecules. When comparing cisplatin and PIFA-treated tumours with
      cisplatin alone treated tumours we found overall less gammaH2AX, a measure for
      DNA damage. Taken together, we have identified an intricate network of
      lysophospholipid signalling by splenic macrophages that induces systemic
      chemoresistance in vivo via an altered DNA damage response. 

PMID- 25387472
TI  - The warrior in the machine: neuroscience goes to war.
AB  - Ever since Stone Age men discovered that knapping flint produced sharp stone
      edges that could be used in combat as well as for cooking and hunting,
      technological advances of all kinds have been adapted and adopted by the
      military.The opportunities provided by modern neuroscience are proving no
      exception, but their application in a military context is accompanied by complex
      practical and ethical considerations.

PMID- 25387473
TI  - Polyunsaturated fatty acids and their metabolites in brain function and disease.
AB  - The brain is highly enriched with fatty acids. These include the polyunsaturated
      fatty acids (PUFAs) arachidonic acid and docosahexaenoic acid, which are largely
      esterified to the phospholipid cell membrane. Once PUFAs are released from the
      membrane, they can participate in signal transduction, either directly or after
      enzymatic conversion to a variety of bioactive derivatives ('mediators'). PUFAs
      and their mediators regulate several processes within the brain, such as
      neurotransmission, cell survival and neuroinflammation, and thereby mood and
      cognition. PUFA levels and the signalling pathways that they regulate are altered
      in various neurological disorders, including Alzheimer's disease and major
      depression. Diet and drugs targeting PUFAs may lead to novel therapeutic
      approaches for the prevention and treatment of brain disorders. 

PMID- 25387474
TI  - Increased peritoneal damage in glyoxalase 1 knock-down mice treated with
      peritoneal dialysis.
AB  - BACKGROUND: Peritoneal dialysis (PD) is limited by peritoneal fibrosis and
      ultrafiltration failure. This is in part caused by the high concentration of
      glucose degradation products (GDPs) present in PD fluids (PDF) as a consequence
      of heat sterilization. Existing research in long-term PD has mainly dealt with
      the toxicity induced by GDPs and the development of therapeutic strategies to
      reduce the cellular burden of GDPs. Currently, there are few data regarding the
      potential role of detoxification systems of GDP in PD. In this study, the role of
      glyoxalase 1 (Glo1), the major detoxification pathway for dicarbonyl-derived GD
      such as methylglyoxal (MG) and glyoxal (Gx), was investigated in vivo using
      heterozygous knock-down mice for Glo1 (Glo1(-/+)). METHODS: Wild-type (WT) and
      Glo1(-/+) mice were repeatedly treated with PDF containing low and high amounts
      of GDP, particularly with respect to the content of dicarbonyls. After 12 weeks
      of treatment with PDF, peritoneal damage and function were evaluated. RESULTS:
      Glo1(-/+) mice treated with PDF showed increased formation of advanced glycation
      endproduct (AGE) when compared with WT mice, particularly the Gx-derived AGE,
      carboxymethyl-lysine. This was associated with increased inflammation,
      neovascularization, increased peritoneal fibrosis and impaired peritoneal
      function. CONCLUSIONS: This study suggests a pivotal and underestimated role for
      Glo1 as a detoxifying enzyme in GDP-associated peritoneal toxicity in PD. The
      indirect and direct modulation of Glo1 may therefore offer a new therapeutic
      option in prevention of GDP-induced peritoneal damage in PD.

PMID- 25387475
TI  - The intestine-renal connection in IgA nephropathy.
AB  - It is commonly stated that mucosal immunity plays a role in the pathogenesis of
      IgA nephropathy (IgAN); however, the search for specific eliciting factors has
      been largely inconclusive. A dysregulated mucosal immune system with defective
      immune tolerance to commonly encountered pathogens or alimentary components is
      likely to be the key factor in triggering IgAN. Most of the interest,
      particularly in Asia, was being focussed on the possibility of modulating the
      mucosal immune system by tonsillectomy, a simple way of eradicating a source of
      pathogens, meanwhile reducing mucosal-associated immune system (mucosal
      associated lymphoid tissue, MALT), but results are still inconclusive. Over the
      last years, a resurgence of interest has addressed the role of intestinal
      immunity facing dietary components, like gluten or the complex intestinal flora,
      the microbiota. The latter is focussing particular interest in recent reports,
      because it can vary according to diet and environmental factors, is modulated by
      the host genes and influences, in return, the MALT activity. Some data suggest a
      tempting new hypothesis for a strong intestine-kidney connection in IgAN. A
      defective immune tolerance might favour an abnormal response to microbiota with
      alterations of the intestinal barrier, including increased alimentary antigens
      and bacterial toxins absorption, triggering MALT activation and subclinical
      intestinal inflammation. This can produce abnormal response to alimentary
      antigens or commensal microbes with synthesis of aberrantly glycosylated
      polymeric IgA1 which eventually enter the circulation with renal deposits
      formation. The hypothesis is tempting also because it offers new treatment
      options, targeted to subclinical intestinal inflammation or microbiota
      modifications. 

PMID- 25387476
TI  - Response to: 'Is primary Sjogren's syndrome an orphan disease? A critical
      appraisal of prevalence studies in Europe' by Cornec and Chiche.

PMID- 25387477
TI  - Golimumab administered subcutaneously every 4 weeks in ankylosing spondylitis: 5
      year results of the GO-RAISE study.
AB  - OBJECTIVE: Assess golimumab efficacy/safety through 5 years in patients with
      active ankylosing spondylitis (AS). METHODS: 356 patients with AS were randomly
      assigned to placebo, golimumab 50 mg or 100 mg every 4 weeks. At week 16,
      patients with inadequate response early escaped with blinded dose adjustments
      (placebo to 50 mg, 50 mg to 100 mg). At week 24, all patients receiving placebo
      crossed over to 50 mg. Blinded active therapy continued through week 104; from
      week 104 to week 252, the golimumab dose could be adjusted. Intent-to-treat and
      observed efficacy data were assessed by randomised treatment groups. RESULTS: At
      week 256, and with >4.5 years of golimumab, overall intent-to-treat Assessment in
      SpondyloArthritis international Society criteria for 20% improvement (ASAS20) and
      ASAS40 response rates were 66.0% (235/356) and 57.0% (203/356), respectively;
      Bath AS Disease Activity Index 50% improvement response was 55.9% (199/356).
      Observed response rates among the 255 (72%) patients who continued golimumab
      through week 252 were consistent, albeit somewhat higher. Among patients who
      increased golimumab from 50 to 100 mg, 60.6% (20/33) and 44.7% (17/38) achieved
      ASAS20/ASAS40 responses, respectively, following >=2 consecutive doses of
      golimumab 100 mg. Golimumab safety through week 268 was similar to that through
      week 24 regardless of dose. CONCLUSIONS: Clinical improvements observed in
      patients treated with golimumab through week 24 were sustained through week 256
      (5 years). Long-term golimumab safety is consistent with that of other
      established tumour-necrosis-factor-antagonists. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov: NCT00265083.

PMID- 25387478
TI  - Comparative evaluation of group-based mindfulness-based stress reduction and
      cognitive behavioral therapy for the treatment and management of chronic pain
      disorders: protocol for a systematic review and meta-analysis with indirect
      comparisons.
AB  - BACKGROUND: Chronic pain disorders impact the physical, psychological, social,
      and financial well-being of between 10%-30% of Canadians. The primary aims of
      psychological interventions targeting chronic pain disorders are to reduce
      patients' pain-related disability and to improve their quality of life. Cognitive
      behavioral therapy (CBT) is the prevailing treatment for chronic pain, however
      mindfulness-based stress reduction (MBSR) has displayed promise as an alternative
      treatment option. The objective of this systematic review and meta-analysis is to
      compare MBSR to CBT in their relative ability to reduce pain-related disability
      and intensity, to alleviate emotional distress, and to improve global functioning
      in chronic pain patients. METHODS/DESIGN: We will conduct a systematic review
      with meta-analyses to compare MBSR to CBT in the treatment of chronic pain
      disorders in adults. We will report our review according to the recommendations
      provided by the PRISMA statement. Randomized studies will be included and the
      literature search will comprise Ovid MEDLINE(r), Ovid MEDLINE(r) In-Process &
      Other Non-Indexed Citations, Embase Classic+Embase, PsycINFO, the Cochrane
      Library on Wiley, including CENTRAL, Cochrane Database of Systematic Reviews,
      DARE, and HTA. Study selection and data extraction will be conducted by
      independent investigators and in duplicate. Outcomes of interest will include
      pain interference, pain intensity, emotional functioning, and patient global
      impression of change. The Cochrane risk of bias tool will be used to assess risk
      of bias of included studies. As we anticipate that scales used to measure
      participant responses will be related but varied from study to study,
      standardized mean differences will be used to compare effect sizes between
      treatment modalities. Given the possibility of little or no head-to-head evidence
      comparing MBSR with CBT, we will use indirect treatment comparison methodology to
      assess the relative effectiveness of these interventions. DISCUSSION: The
      findings from this study will assist patients and treatment providers to make
      informed decisions regarding evidence-based treatment selection for chronic pain
      disorders. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009356.

PMID- 25387479
TI  - Attention dysfunction subtypes of developmental dyslexia.
AB  - BACKGROUND: Previous studies indicate that many different aspects of attention
      are impaired in children diagnosed with developmental dyslexia (DD). The
      objective of the present study was to identify cognitive profiles of DD on the
      basis of attentional test performance. MATERIAL/METHODS: 78 children with DD (30
      girls, 48 boys, mean age of 12 years +/-8 months) and 32 age- and sex-matched non
      dyslexic children (14 girls, 18 boys) were examined using a battery of
      standardized tests of reading, phonological and attentional processes (alertness,
      covert shift of attention, divided attention, inhibition, flexibility, vigilance,
      and visual search). Cluster analysis was used to identify subtypes of DD.
      RESULTS: Dyslexic children showed deficits in alertness, covert shift of
      attention, divided attention, flexibility, and visual search. Three different
      subtypes of DD were identified, each characterized by poorer performance on the
      reading, phonological awareness, and visual search tasks. Additionally, children
      in cluster no. 1 displayed deficits in flexibility and divided attention. In
      contrast to non-dyslexic children, cluster no. 2 performed poorer in tasks
      involving alertness, covert shift of attention, divided attention, and vigilance.
      Cluster no. 3 showed impaired covert shift of attention. CONCLUSIONS: These
      results indicate different patterns of attentional impairments in dyslexic
      children. Remediation programs should address the individual child's deficit
      profile.

PMID- 25387480
TI  - Hybridization approach to in-line and off-axis (electron) holography for superior
      resolution and phase sensitivity.
AB  - Holography--originally developed for correcting spherical aberration in
      transmission electron microscopes--is now used in a wide range of disciplines
      that involve the propagation of waves, including light optics, electron
      microscopy, acoustics and seismology. In electron microscopy, the two primary
      modes of holography are Gabor's original in-line setup and an off-axis approach
      that was developed subsequently. These two techniques are highly complementary,
      offering superior phase sensitivity at high and low spatial resolution,
      respectively. All previous investigations have focused on improving each method
      individually. Here, we show how the two approaches can be combined in a
      synergetic fashion to provide phase information with excellent sensitivity across
      all spatial frequencies, low noise and an efficient use of electron dose. The
      principle is also expected to be widely to applications of holography in light
      optics, X-ray optics, acoustics, ultra-sound, terahertz imaging, etc.

PMID- 25387481
TI  - Assessment of vitamin D and its association with cardiovascular disease risk
      factors in an adult migrant population: an audit of patient records at a
      Community Health Centre in Kensington, Melbourne, Australia.
AB  - BACKGROUND: Vitamin D deficiency is a global public health problem associated
      with increased risk of cardio-metabolic diseases and osteoarthritis. Migrants
      with dark skin settled in temperate climates are at greater risk of both vitamin
      D deficiency and cardiovascular diseases. This study aims to identify the risk of
      vitamin D deficiency and associations with cardiovascular disease in a migrant
      population in Australia. METHODS: An audit was carried out at a Community Health
      Service in Kensington, Melbourne which, services a large migrant population. Data
      from the clinical records of all adults who visited the medical centre at least
      once during the period from 1st January 2010 to 31st December 2012 was extracted.
      The future (10 year) coronary heart disease risk was estimated using Framingham
      Risk Score. RESULTS: The centre has given higher priority to vitamin D testing in
      migrants, those middle-aged, females and those with diabetes and osteoarthritis.
      Migrants from countries located in lower latitude regions (Latitude N230 to S230)
      were 1.48 (95% C.I. 1.32-1.65) times more likely to develop vitamin D deficiency
      post migration and 0.44 (95% C.I. 0.31-0.62) times less likely to have a >15% 10
      year risk of coronary heart disease when compared to their Australian-born
      counterparts. CONCLUSIONS: Adherence to a high risk strategy for vitamin D
      testing was observed in the centre. Pre-migration latitude is an important factor
      for vitamin D deficiency (lower the latitude higher the risk) and in predicting
      future risk of cardiovascular disease in migrants. These findings suggest that a
      targeted approach for vitamin D testing, including zone of origin might better
      identify individuals at higher risk of both vitamin D deficiency and
      cardiovascular disease.

PMID- 25387482
TI  - A painful nodule on the leg: a quiz. Diagnosis: Low-grade cutaneous pilar
      leiomyosarcoma.

PMID- 25387484
TI  - Medical education and the healthcare system--why does the curriculum need to be
      reformed?
AB  - Medical education has been the subject of ongoing debate since the early 1900s.
      The core of the discussion is about the importance of scientific knowledge on
      biological understanding at the expense of its social and humanistic
      characteristics. Unfortunately, reforms to the medical curriculum are still based
      on a biological vision of the health-illness process. In order to respond to the
      current needs of society, which is education's main objective, the learning
      processes of physicians and their instruction must change once again. The
      priority is the concept of the health-illness process that is primarily social
      and cultural, into which the biological and psychological aspects are inserted. A
      new curriculum has been developed that addresses a comprehensive instruction of
      the biological, psychological, social, and cultural (historical) aspects of
      medicine, with opportunities for students to acquire leadership, teamwork, and
      communication skills in order to introduce improvements into the healthcare
      systems where they work. 

PMID- 25387483
TI  - Lymphatic filariasis control in Tanga Region, Tanzania: status after eight rounds
      of mass drug administration.
AB  - BACKGROUND: Lymphatic filariasis (LF) control started in Tanga Region of Tanzania
      in 2004, with annual ivermectin/albendazole mass drug administration (MDA). Since
      then, the current project has monitored the effect in communities and schools in
      rural areas of Tanga District. In 2013, after 8 rounds of MDA, spot check surveys
      were added in the other 7 districts of Tanga Region, to assess the regional LF
      status. METHODS: LF vector and transmission surveillance, and human cross
      sectional surveys in communities and schools, continued in Tanga District as
      previously reported. In each of the other 7 districts, 2-3 spot check sites were
      selected and about 200 schoolchildren were examined for circulating filarial
      antigens (CFA). At 1-2 of the sites in each district, additional about 200
      community volunteers were examined for CFA and chronic LF disease, and the CFA
      positives were re-examined for microfilariae (mf). RESULTS: The downward trend in
      LF transmission and human infection previously reported for Tanga District
      continued, with prevalences after MDA 8 reaching 15.5% and 3.5% for CFA and mf in
      communities (decrease by 75.5% and 89.6% from baseline) and 2.3% for CFA in
      schoolchildren (decrease by 90.9% from baseline). Surprisingly, the prevalence of
      chronic LF morbidity after MDA 8 was less than half of baseline records. No
      infective vector mosquitoes were detected after MDA 7. Spot checks in the other
      districts after MDA 8 showed relatively high LF burdens in the coastal districts.
      LF burdens gradually decreased when moving to districts further inland and with
      higher altitudes. CONCLUSION: LF was still widespread in many parts of Tanga
      Region after MDA 8, in particular in the coastal areas. This calls for
      intensified control, which should include increased MDA treatment coverage,
      strengthening of bed net usage, and more male focus in LF health information
      dissemination. The low LF burdens observed in some inland districts suggest that
      MDA in these could be stepped down to provide more resources for upscale of
      control in the coastal areas. Monitoring should continue to guide the programme
      to ensure that the current major achievements will ultimately lead to successful
      LF elimination.

PMID- 25387485
TI  - Tackling the problem of blood culture contamination in the intensive care unit
      using an educational intervention.
AB  - Blood culture contamination (BCC) has been associated with unnecessary antibiotic
      use, additional laboratory tests and increased length of hospital stay thus
      incurring significant extra hospital costs. We set out to assess the impact of a
      staff educational intervention programme on decreasing intensive care unit (ICU)
      BCC rates to <3% (American Society for Microbiology standard). BCC rates during
      the pre-intervention period (January 2006-May 2011) were compared with the
      intervention period (June 2011-December 2012) using run chart and regression
      analysis. Monthly ICU BCC rates during the intervention period were reduced to a
      mean of 3.7%, compared to 9.5% during the baseline period (P < 0.001) with an
      estimated potential annual cost savings of about L250,100. The approach used was
      simple in design, flexible in delivery and efficient in outcomes, and may
      encourage its translation into clinical practice in different healthcare
      settings.

PMID- 25387486
TI  - Small animal image-guided radiotherapy: status, considerations and potential for
      translational impact.
AB  - Radiation biology is being transformed by the implementation of small animal
      image-guided precision radiotherapy into pre-clinical research programmes
      worldwide. We report on the current status and developments of the small animal
      radiotherapy field, suggest criteria for the design and execution of effective
      studies and contend that this powerful emerging technology, used in combination
      with relevant small animal models, holds much promise for translational impact in
      radiation oncology. 

PMID- 25387487
TI  - Validation and clinicopathologic associations of a urine-based bladder cancer
      biomarker signature.
AB  - BACKGROUND: To validate the expression of a urine-based bladder cancer associated
      diagnostic signature comprised of 10 targets; ANG, CA9, MMP9, MMP10, SERPINA1,
      APOE, SDC1, VEGFA, SERPINE1 and IL8 in bladder tumor tissues. METHODS:
      Immunohistochemical analyses were performed on tumor specimens from 213 bladder
      cancer patients (transitional cell carcinoma only) and 74 controls. Staining
      patterns were digitally captured and quantitated (Aperio, Vista, CA), and
      expression was correlated with tumor stage, tumor grade and outcome measures.
      RESULTS: We revealed a positive association of 9 of the 10 proteins (excluding
      VEGF) in bladder cancer. Relative to control cases, a reduction in SDC1 and
      overexpression of MMP9, MMP10, SERPINE1, IL8, APOE, SERPINA1, ANG were associated
      with high stage bladder cancer. Reduced VEGF and increased SERPINA1 were
      associated with high-grade bladder cancer. Disease-specific survival was
      significantly reduced in tumors with high expression of SERPINE1 and/or IL8.
      CONCLUSIONS: These findings confirm that the proteins in a urine-based diagnostic
      signature are aberrantly expressed in bladder tumor tissues, and support the
      potential additional utility of selected biomarkers for the clinicopathological
      evaluation of excised tissue or biopsy material. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_200.

PMID- 25387488
TI  - Hydrogen production via supercritical water gasification of bagasse using Ni
      Cu/gamma-Al2O3 nano-catalysts.
AB  - Biomass gasification in supercritical water media is a promising method for the
      production of hydrogen. In this research, Cu-promoted Ni/gamma-Al2O3 nano
      catalysts were prepared with 2.5-30 wt% Ni and 0.6-7.5 wt% Cu loadings via the
      microemulsion method. Nano-catalysts were characterized by inductively coupled
      plasma (ICP), Brunauer Emmett Teller (BET) technique, X-Ray Diffraction (XRD), H2
      chemisorption and Transmission Electron Microscopy (TEM) technique, as well as
      Carbon-Hydrogen-Nitrogen-Sulfur (CHNS) analysis was carried out for elemental
      analysis of bagasse. Nano-catalysts were assessed in a batch micro-reactor under
      400 degrees C and 240 bar. The microemulsion method decreased the catalyst
      average particle size and increased the percentage dispersion and reduction of
      the catalysts. The total gas yield increased with an increase in Ni and Cu
      loadings up to 20 wt% Ni and 5 wt% Cu and then started to decrease. Using the
      microemulsion technique for the preparation of Ni-Cu/gamma-Al2O3 nano-catalyst,
      increased the hydrogen yield to 11.76 (mmol of H2/g of bagasse), CO yield to 2.67
      (mmol of CO/g of bagasse) and light gaseous hydrocarbons to 0.6 (mmol of light
      gaseous hydrocarbons/g of bagasse). Promotion of Ni/gamma-Al2O3 with copper
      increased the mole fraction of hydrogen in the final gasification products to
      58.1 mol%.

PMID- 25387489
TI  - Aerobic training suppresses exercise-induced lipid peroxidation and inflammation
      in overweight/obese adolescent girls.
AB  - This study aimed to determine whether aerobic training could reduce lipid
      peroxidation and inflammation at rest and after maximal exhaustive exercise in
      overweight/obese adolescent girls. Thirty-nine adolescent girls (14-19 years old)
      were classified as nonobese or overweight/obese and then randomly assigned to
      either the nontrained or trained group (12-week multivariate aerobic training
      program). Measurements at the beginning of the experiment and at 3 months
      consisted of body composition, aerobic fitness (VO2peak) and the following blood
      assays: pre- and postexercise lipid peroxidation (15F2a-isoprostanes [F2-Isop],
      lipid hydroperoxide [ROOH], oxidized LDL [ox-LDL]) and inflammation
      (myeloperoxidase [MPO]) markers. In the overweight/ obese group, the training
      program significantly increased their fat-free mass (FFM) and decreased their
      percentage of fat mass (%FM) and hip circumference but did not modify their
      VO2peak. Conversely, in the nontrained overweight/obese group, weight and %FM
      increased, and VO2peak decreased, during the same period. Training also prevented
      exercise-induced lipid peroxidation and/or inflammation in overweight/obese girls
      (F2-Isop, ROOH, ox-LDL, MPO). In addition, in the trained overweight/obese group,
      exercise-induced changes in ROOH, ox-LDL and F2-Isop were correlated with
      improvements in anthropometric parameters (waist-to-hip ratio, %FM and FFM). In
      conclusion aerobic training increased tolerance to exercise-induced oxidative
      stress in overweight/obese adolescent girls partly as a result of improved body
      composition. 

PMID- 25387491
TI  - Lower facial remodeling with botulinum toxin type A for the treatment of masseter
      hypertrophy.
AB  - BACKGROUND: Masseter hypertrophy has been treated with botulinum toxin injections
      because of esthetic complaints especially in Asians. OBJECTIVES: The goal of the
      present study was to evaluate the efficacy of abobotulin toxin use in masseter
      hipertrophy treatment in Brazilians. METHODS: Ten Brazilian female patients with
      masseter hypertrophy were subjected to injections of 90U of abobotulinum toxin A
      applied on each side respecting the safety zone stabilished in literature and
      were followed up for 24 weeks. RESULTS: When analyzing the coefficients between
      measures of middle and lower third of the face obtained from standardized
      photographs, an increase was observed, with statistical significance at 2 weeks
      (p=0.005) and 12 weeks (p=0.001). The progression of lower third reduction was
      3.94%, 5.26%, 11.99%, and 5.47% (2, 4, 12, and 24 weeks respectively). All
      patients showed improvement in bruxism after treatment. Observed adverse effects
      were masticatory fatigue, smile limitation, and smile asymmetry. CONCLUSION: The
      use of abobotulinum toxin A for masseter hypertrophy is effective in Brazilians
      and reached its maximum effect of facial thinning at 12 weeks. Smile limitation
      had a higher incidence compared to that reported in the literature and may result
      from risorius muscle blockage caused by toxin dissemination. Despite its side
      effects, 80% of the patients would like to repeat the treatment.

PMID- 25387490
TI  - Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and
      treatment.
AB  - Researches on DH have shown that it is not just a bullous skin disease, but a
      cutaneous-intestinal disorder caused by hypersensitivity to gluten. Exposure to
      gluten is the starting point of an inflammatory cascade capable of forming
      autoantibodies that are brought to the skin, where they are deposited,
      culminating in the formation of skin lesions. These lesions are vesico-bullous,
      pruritic, and localized especially on elbows, knees and buttocks, although
      atypical presentations can occur. Immunofluorescence of perilesional area is
      considered the gold standard for diagnosis, but serological tests help in cases
      where it is negative. Patients who follow gluten-free diets have better control
      of symptoms on the skin and intestine, as well as lower risks of progression to
      lymphoma. Dapsone remains the main drug for treatment, but it requires monitoring
      of possible side effects, some potentially lethal.

PMID- 25387492
TI  - Immunofluorescence testing in the diagnosis of autoimmune blistering diseases:
      overview of 10-year experience.
AB  - BACKGROUND: Immunofluorescence testing is an important tool for diagnosing
      blistering diseases. OBJECTIVE: To characterize the immunofluorescence findings
      in patients diagnosed with autoimmune blistering skin diseases. METHODS: We
      retrospectively analyzed immunofluorescence results encompassing a 10-year
      period. RESULTS: 421 patients were included and divided into 2 groups: group 1-
      intraepidermal blistering diseases (n=277) and 2- subepidermal blistering
      diseases (n=144). For group 1, positive DIF findings demonstrated: predominance
      of IgG intercellular staining (ICS) and C3 for pemphigus foliaceus-PF (94% and
      73% respectively), pemphigus vulgaris-PV (91.5%-79.5%) and paraneoplastic
      pemphigus-PNP (66%-33%); ICS IgA in 100% of IgA pemphigus cases, and IgG deposits
      in the basement membrane zone (BMZ) along with ICS in one Hailey-Hailey patient.
      The IIF findings revealed mean titers of 1:2.560 for PV and 1:1.280 for PF. For
      paraneoplastic pemphigus, IIF was positive in 2 out of 3 cases with rat bladder
      substrate. In group 2, positive DIF findings included multiple deposits at
      basement membrane zone for epidermolysis bullosa acquisita-EBA (C3-89%,IgG
      79%,IgA-47%,IgM-21%) mucous membrane pemphigoid-MMP (C3,IgG,IgA,IgM-80%) and
      bullous pemphigoid-BP (C3-91%,IgG-39%,IgA-11%,IgM-6%), and IgA at basement
      membrane zone for IgA linear disease (99%) and dermatitis herpetiformis-DH
      (dermal papillae in 84.6%). For lichen planus pemphigoides, there was C3 (100%)
      and IgG (50%) deposition at basement membrane zone. indirect immunofluorescence
      positive findings revealed basement membrane zone IgG deposits in 46% of BP
      patients, 50% for EBA, 15% for IgA linear dermatosis and 50% for LPP. Indirect
      immunofluorescence positive results were higher for BP and EBA with Salt-Split
      skin substrate. CONCLUSION: Our results confirmed the importance of
      immunofluorescence assays in diagnosing autoimmune blistering diseases, and
      higher sensitivity for indirect immunofluorescence when Salt-split skin technique
      is performed.

PMID- 25387493
TI  - Expression of lymphatic markers and lymphatic growth factors in psoriasis before
      and after anti-TNF treatment.
AB  - BACKGROUND: Angiogenesis is an early stage of psoriatic lesion development, but
      less is known about lymphagiogenesis and its role in the development of
      psoriasis. OBJECTIVE: To examine the expression of specific lymphatic markers and
      lymphatic growth factors in untreated psoriatic skin, in the unaffected skin of
      patients and skin of healthy volunteers, as well as their alteration after
      treatment with an anti-TNF agent. METHODS: Immunohistochemistry for the lymphatic
      markers D2-40 and LYVE-1, in addition to the VEGF-C and VEGF-D growth factors,
      was performed in the skin biopsies of psoriatic lesions and adjacent non
      psoriatic skin of 19 patients before and after treatment with etanercept, as well
      as in the skin biopsies of 10 healthy volunteers. RESULTS: The expressions of D2
      40, VEGF-C and VEGF-D on lymphatic vessels underwent statistically significant
      increases in untreated psoriatic skin compared with non-lesional skin, in
      contrast to LYVE-1, which did not involve significant increase in expression in
      psoriatic skin. VEGF-C expression on lymphatic vessels diminished after treatment
      with etanercept. Moreover VEGF-C and VEGF-D staining on fibroblasts presented
      with higher expression in lesional skin than in non-lesional adjacent skin.
      CONCLUSION: Remodeling of lymphatic vessels possibly occurs during psoriatic
      lesion development, parallel to blood vessel formation. The exact role of this
      alteration is not yet clear and more studies are necessary to confirm these
      results.

PMID- 25387494
TI  - Phototherapy promotes healing of cutaneous wounds in undernourished rats.
AB  - BACKGROUND: Various studies have shown that phototherapy promotes the healing of
      cutaneous wounds. OBJECTIVE: To investigate the effect of phototherapy on healing
      of cutaneous wounds in nourished and undernourished rats. METHODS: Forty rats, 20
      nourished plus 20 others rendered marasmus with undernourishment, were assigned
      to four equal groups: nourished sham, nourished Light Emitting Diode treated,
      undernourished sham and undernourished Light Emitting Diode treated. In the two
      treated groups, two 8-mm punch wounds made on the dorsum of each rat were
      irradiated three times per week with 3 J/cm2 sq cm of combined 660 and 890 nm
      light; wounds in the other groups were not irradiated. Wounds were evaluated with
      digital photography and image analysis, either on day 7 or day 14, with biopsies
      obtained on day 14 for histological studies. RESULTS: Undernourishment retarded
      the mean healing rate of the undernourished sham wounds (p < 0.01), but not the
      undernourished Light emission diode treated wounds, which healed significantly
      faster (p < 0.001) and as fast as the two nourished groups. Histological analysis
      showed a smaller percentage of collagen in the undernourished sham group compared
      with the three other groups, thus confirming our photographic image analysis
      data. CONCLUSION: Phototherapy reverses the adverse healing effects of
      undernourishment. Similar beneficial effects may be achieved in patients with
      poor nutritional status.

PMID- 25387495
TI  - Piercings in medical students and their effects on the skin.
AB  - BACKGROUND: Piercings are body embellishments commonly seen in young people,
      however their inherent risk of infection and scarring disorders are less
      divulged. OBJECTIVE: To evaluate the prevalence of body piercings among medical
      students and their possible dermatologic consequences. METHODS: Cross-sectional
      study with 58 medical students, by means of a structured questionnaire covering
      socio-demographic characteristics, technical issues related to the piercing and
      characteristics of the dermatologic complications. RESULTS: The sample was
      predominantly female (86.2%), with mean age 24 +/- 3 years. The placement of the
      first piercing occurred during adolescence (median age 15), without medical
      supervision (91.4%) or knowledge of parents/guardians (74%). Most piercings were
      made of metal alloy/stainless steel, in a dumbbell model (51.7%), inserted in the
      umbilical area (53.5%) or ear (41.4%), with frequent cutaneous reactions in the
      first six months post-piercing. Hypertrophic scarring, pain, swelling and
      infection (p<0.05) had significantly higher frequencies among those with navel
      piercings. CONCLUSION: Piercing insertion occurred during adolescence. Local
      inflammatory and infectious reactions were common. Scarring disorders and
      dermatitis appeared in the long term. There is need for preventive and
      educational activities, starting with those in the academic environment.

PMID- 25387496
TI  - Long-term results of oxybutynin use in treating facial hyperhidrosis.
AB  - BACKGROUND: Facial hyperhidrosis can lead to serious emotional distress. Video
      assisted thoracic sympathectomy resolves symptoms effectively, though it may be
      associated with compensatory hyperhidrosis, which may be more common in patients
      undergoing resection of the second thoracic ganglion. Oxybutynin has been used as
      a pharmacological approach to facial hyperhidrosis but the long-term results of
      this treatment are unclear. OBJECTIVE: To evaluate the use of low oxybutynin
      doses in facial hyperhidrosis patients for at least six months. METHODS: 61
      patients were monitored for over six months and assessed according to the
      following variables: impact of hyperhidrosis on quality of life (QOL) before
      treatment and after six weeks, evolution of facial hyperhidrosis after six weeks
      and at the last consultation, complaints of dry mouth after six weeks and on last
      return visit, and improvement at other hyperhidrosis sites. RESULTS: Patients
      were monitored for 6 to 61 months (median=17 months). Thirty-six (59%) were
      female. Age ranged from 17-74 (median:45). Pre-treatment QOL was poor/very poor
      in 96.72%. After six weeks, 100% of patients improved QOL. Comparing results
      after six weeks and on the last visit, 91.8% of patients maintained the same
      category of improvement in facial hyperhidrosis, 3.3% worsened and 4.9% improved.
      Dry mouth complaints were common but not consistent throughout treatment. More
      than 90% of patients presented moderate/great improvement at other hyperhidrosis
      sites. CONCLUSION: Patients who had a good initial response to treatment
      maintained a good response long-term, did not display tachiphylaxis and
      experienced improvement on other hyperhidrosis sites.

PMID- 25387497
TI  - Field work I: selecting the instrument for data collection.
AB  - The selection of instruments that will be used to collect data is a crucial step
      in the research process. Validity and reliability of the collected data and,
      above all, their potential comparability with data from previous investigations
      must be prioritized during this phase. We present a decision tree, which is
      intended to guide the selection of the instruments employed in research projects.
      Studies conducted along these lines have greater potential to broaden the
      knowledge on the studied subject and contribute to addressing truly socially
      relevant needs.

PMID- 25387500
TI  - Targetoid hemosiderotic hemangioma - Case report.
AB  - Targetoid Hemosiderotic Hemangioma, also known as Hobnail Hemangioma, is a lesion
      of vascular origin, probably lymphatic. The most common clinical feature is a
      solitary violaceous papule surrounded by a pale, thin area and a peripheral
      ecchymotic ring, simulating a target. Histopathologically, there is a biphasic
      pattern, with dilated vessels in the superficial dermis and
      pseudoangiosarcomatous pattern in the deep dermis, and endothelial cells with
      hobnail morphology. A simple excision is curative. We report a rare case of
      Targetoid Hemosiderotic Hemangioma.

PMID- 25387498
TI  - Update on cutaneous tuberculosis.
AB  - Tuberculosis continues to draw special attention from health care professionals
      and society in general. Cutaneous tuberculosis is an infection caused by M.
      tuberculosis complex, M. bovis and bacillus Calmette-Guerin. Depending on
      individual immunity, environmental factors and the type of inoculum, it may
      present varied clinical and evolutionary aspects. Patients with HIV and those
      using immunobiological drugs are more prone to infection, which is a great
      concern in centers where the disease is considered endemic. This paper aims to
      review the current situation of cutaneous tuberculosis in light of this new
      scenario, highlighting the emergence of new and more specific methods of
      diagnosis, and the molecular and cellular mechanisms that regulate the parasite
      host interaction.

PMID- 25387499
TI  - Surgical treatment of axillary hyperhidrosis by suction-curettage of sweat
      glands.
AB  - Suction curettage is a dermatologic surgery technique for the treatment of
      axillary hyperhidrosis, which is becoming more popular. OBJECTIVE: The purpose of
      this study is to describe the current technique of removal of axillary sweat
      glands, and evaluate its efficacy and safety. CONCLUSION: Suction-curettage of
      sweat glands is a minimally invasive surgical technique that is easy to perform,
      safe, has high rates of success and relatively few side-effects. It is generally
      well tolerated by patients and requires shorter time away from daily activities,
      when compared with other surgical modalities.

PMID- 25387501
TI  - Cutaneous involvement as the initial presentation of metastatic breast
      adenocarcinoma - Case report.
AB  - Cutaneous metastasis is an uncommon manifestation of visceral malignancy. It
      occurs late in the course of the disease but can be a sign of an unknown
      neoplasm. A case of local cutaneous metastasis by contiguity with breast
      adenocarcinoma is reported. It presented as initial manifestation and main
      complaint of a 68-year-old woman, with no family history and negative screening
      tests for the disease. Biopsies of ulcers which do not heal, persistent hardened
      erythema and cutaneous nodules of unknown cause must be performed, since the
      evidence of cutaneous metastasis can be of extreme importance for the diagnosis,
      staging and prognosis of an internal cancer. In this scenario, the dermatologist
      plays a fundamental role and should be always attentive to this diagnostic
      possibility.

PMID- 25387502
TI  - Tumor of follicular infundibulum with unique features.
AB  - Tumor of the follicular infundibulum is a rare benign cutaneous adnexal neoplasm
      with variable clinical presentation. In most cases the diagnosis is made with the
      help of histopathology, due to lack of a characteristic clinical presentation.
      The most common form is a solitary lesion, but it can be multiple or eruptive,
      then called infundibulomatose. This case report illustrates a patient with
      multiple lesions of tumor of the follicular infundibulum with bizarre aspect and
      atypical location.

PMID- 25387503
TI  - Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease.
AB  - Inflammatory bowel diseases can commonly present many cutaneous lesions which can
      contribute to the diagnosis of the disease or its activity. The most frequent
      cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis
      activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous
      stomatitis (4%). Other reactive skin manifestations related to immunological
      mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome,
      arthritis-dermatitis syndrome associated with inflammatory bowel disease and
      leukocytoclastic vasculitis. We describe the case of a young man with diagnosis
      of ulcerative rectocolitis, which presented an extensive cutaneous gangrene
      secondary to microvascular thrombosis. The case represents a dermatologic rarity
      and should be recognized as a cutaneous manifestation related to the
      hypercoagulability state observed in the disease's activity.

PMID- 25387504
TI  - Malignant syphilis in an immunocompetent female patient.
AB  - Malignant syphilis is an uncommon manifestation of secondary syphilis, in which
      necrotic lesions may be associated with systemic signs and symptoms. Generally it
      occurs in an immunosuppressed patient, mainly HIV-infected, but might be observed
      on those who have normal immune response. Since there is an exponential increase
      in the number of syphilis cases, more diagnoses of malignant syphilis must be
      expected. We report a case in an immunocompetent female patient.

PMID- 25387505
TI  - American tegumentary leishmaniasis - a case of therapeutic challenge.
AB  - American Tegumentary Leishmaniasis (ATL) is a chronic, non-contagious, infectious
      disease affecting millions of people worldwide. The timely and proper treatment
      is of great importance to prevent the disease from progressing to destructive and
      severe forms. Treatment for ATL recommended by the Brazilian Ministry of Health
      is similar for the whole country, regardless of the species of Leishmania. It is
      known that the response to treatment may vary with the strain of the parasite,
      the immune status of the patient and clinical form. We report the case of a
      healthy patient, coming from Manaus, Amazonas state, Brazil, who presented
      resistance to treatment with N-methyl-glutamine and liposomal amphotericin B,
      only being healed after using pentamidine.

PMID- 25387506
TI  - Rigid swelling of sublingual caruncle area due to the salivary gland duct
      obstruction by a sialolith.
AB  - Sialolithiasis is the presence of calculus within the ductal system of a salivary
      gland. Among the diagnostic methods are inspection, palpation, checking the
      amount of saliva secreted and the identification of a sialolith. The authors
      present the case of a 37-year-old female patient with edema of the submandibular
      area and a bulging sublingual caruncle due to a calculus that obstructed the
      salivary gland ostium. 

PMID- 25387507
TI  - Refractory pemphigus vulgaris treated with rituximab and mycophenolate mofetil.
AB  - The main treatment for pemphigus vulgaris are systemic corticosteroids and
      immunosuppressive agents, but due to adverse reactions and therapeutic failure,
      new drugs such as rituximab and mycophenolate mofetil have been used. In this
      case report are described two cases of severe pemphigus vulgaris refractory to
      various treatments, with resolution after use of rituximab and mycophenolate
      mofetil, associated with corticosteroids. A higher-than-usual dose of rituximab
      was employed, without the occurrence of serious adverse reactions. Mycophenolate
      mofetil was added as adjunctive therapy due to lack of response to azathioprine.

PMID- 25387508
TI  - Herpes zoster-associated acute urinary retention in immunocompetent patient.
AB  - Herpes zoster-associated urinary retention is an uncommon event related to virus
      infection of the S2-S4 dermatome. The possible major reasons are ipsilateral
      hemicystitis, neuritis-induced or myelitis-associated virus infection. We report
      a case of a 65-year-old immunocompetent female patient who presented an acute
      urinary retention after four days under treatment with valacyclovir for gluteal
      herpes zoster. The patient had to use a vesical catheter, was treated with
      antibiotics and corticosteroids and fully recovered after eight weeks.

PMID- 25387509
TI  - Three-dimensional aspects of superficial disseminated porokeratosis with scanning
      electron microscopy.
AB  - The three-dimensional findings of the surface and from a cross section from a
      case of disseminated superficial porokeratois using scanning electron microscopy
      are reported. On the surface of the skin, irregular keratin with a serpiginous
      distribution was seen. A gross aspect of keratin in the hyperkeratotic wall was
      also observed and compared to the normal area, in which the release of
      corneocytes seemed normal. The cross-sectional imaging easily identified the
      cornoid lamella, with compact keratin surrounded by normal stratum corneum.

PMID- 25387510
TI  - Goya and tinea favosa.
AB  - A case of a tinea favosa involving the scalp of a child represented in the
      painting "Boys climbing a tree" (Muchachos trepando a un arbol), by Francisco
      Goya y Lucientes, with pictorial representation of favic scutula and consequent
      alopecia. 

PMID- 25387511
TI  - "Sign of the kiss" in dermatitis caused by vesicant beetles ("potos" or Paederus
      sp.).
AB  - The cosmopolitan beetles of the Paederus genus (potos) cause a severe dermatitis
      when the insect is crushed against the skin of exposed areas (the cervical region
      is the most affected). Toxins (pederin and others) from the hemolymph of the
      insect cause plaques and/or bizarre, linear lesions with erythema, edema,
      blisters, pustules, crusts and exulcerations. There may be a burning sensation
      and severe conjunctivitis. Lesions disappear after 10 days and may leave
      hyperchromic macules. Treatment is made with topical corticosteroids and
      intensive washing. 

PMID- 25387512
TI  - Case for diagnosis. Hereditary Hemorrhagic Telangiectasia.
AB  - The Osler-Weber-Rendu syndrome or Hereditary Hemorrhagic Telangiectasia (HHT) is
      a systemic fibrovascular dysplasia characterized by defects in the elastic and
      vascular walls of blood vessels, making them varicose and prone to disruptions.
      Lesions occur in different organs and can lead to hemorrhage in the lungs,
      digestive tract and brain. We describe the case of a patient with cutaneous
      manifestations and severe impairment of the digestive tract. It is important for
      the dermatologist to recognize this syndrome, since the cutaneous lesions may
      play a key role in diagnosis. 

PMID- 25387513
TI  - Case for diagnosis. Lichen Planus.
AB  - Graham-Little-Piccardi-Lassueur Syndrome is a rare form of Lichen Planus,
      characterized by the presence of the triad: non-scarring hair loss in the
      inguinal and axillary regions and follicular spinous or disseminated acuminate
      papules; typical, cutaneous or mucous LP; and scarring alopecia of the scalp with
      or without atrophy. These features do not have to be present simultaneously. 

PMID- 25387514
TI  - Syndrome in question. Costello syndrome.
AB  - Costello syndrome (CS) is a rare genetic disorder, first described by Costello in
      1971, caused by mutations in the HRAS proto-oncogene. Clinical findings include
      facial dysmorphism, skin disorders, cognitive impairment, cardiac and
      musculoskeletal defects. There is an increased risk of malignancies in these
      patients, due to the proto-oncogene mutation, and also sudden death secondary to
      heart disease. We report a case with characteristic phenotype, highlighting the
      peculiar skin changes.

PMID- 25387516
TI  - Distribution of Brazilian dermatologists according to geographic location,
      population and HDI of municipalities: an ecological study.
AB  - This study investigated the geographic distribution of dermatologists in
      Brazilian municipalities in relation to the population, regions of the country
      and human development index. We conducted an ecological study based on data from
      the 2010 census, the 2010 human development index, and the records of the
      Brazilian Society of Dermatology. 5565 municipalities and 6718 dermatologists
      were surveyed. Only 504 (9.1%) municipalities had dermatologists, and accounted
      for 56.2% of the Brazilian population. The smallest population size and lowest
      HDI rate that best discriminated municipalities that did not have dermatologists
      were found to be 28,000 and 0.71, respectively. The average population density of
      dermatologists in cities was 1/23.000 inhabitants, and variations were
      independently associated with the HDI, the population of the municipalities and
      the region of the country.

PMID- 25387515
TI  - The value of trichoscopy in the differential diagnosis of scalp lesions in
      pemphigus vulgaris and pemphigus foliaceus.
AB  - BACKGROUND: Trichoscopy is becoming increasingly popular in diagnosing hair and
      scalp diseases. Scalp involvement in pemphigus is common. The scalp may be the
      first or only site of clinical manifestation of the disease. OBJECTIVE: The aim
      of this study was to analyze whether trichoscopy may be useful in aiding
      differential diagnosis of scalp lesions in patients with pemphigus vulgaris and
      pemphigus foliaceus. METHODS: Trichoscopy was performed in 19 patients with scalp
      lesions in the course of pemphigus (9 patients with pemphigus vulgaris and 10
      with pemphigus foliaceus). In all patients, the diagnosis of scalp pemphigus was
      confirmed by histopathology. The working magnification was 20-fold and 70-fold.
      RESULTS: The most frequently observed trichoscopy features of pemphigus lesions
      were: extravasations (18/19; 94.7%) and yellow hemorrhagic crusts (11/19; 57.9%).
      Yellow dots with whitish halo were observed in 6/19 (31.6%) patients with
      pemphigus. White polygonal structures were observed in pemphigus foliaceus (6/10;
      60%), but not in pemphigus vulgaris. Vascular abnormalities were more frequent in
      pemphigus vulgaris, when compared to pemphigus foliaceus, and were associated
      with a severe course of disease. Linear serpentine vessels were the most frequent
      vascular abnormality in patients with pemphigus vulgaris and pemphigus foliaceus
      (77.8% and 30%, respectively). CONCLUSION: Trichoscopy may serve as a useful
      supplementary method in the differential diagnosis of pemphigus, especially in
      cases of desquamative or exudative lesions limited to the scalp. Extravasations,
      yellow hemorrhagic crusts, yellow dots with whitish halo, white polygonal
      structures and linear serpentine vessels are trichoscopy features which may
      suggest the diagnosis of pemphigus.

PMID- 25387517
TI  - Two cases of renal cell cancer during immunobiologic therapy for psoriasis.
AB  - Immunobiologic therapy is indicated for severe forms of psoriasis, resistant to
      conventional therapy. There is growing concern about their safety profile and
      possible association with cancer development. This article documents two cases of
      renal cell cancer during treatment with biologic therapy, reviewing what is
      described in the literature . The risk of solid tumors as a complication of using
      TNF-alpha inhibitors is controversial. No conclusion can be drawn from the data
      in the literature, however, we believe that special attention should be given to
      those with known risk factors for a specific neoplasm.

PMID- 25387518
TI  - T-cell-predominant lymphoid hyperplasia in a tattoo.
AB  - Cutaneous lymphoid hyperplasia (CLH) can be idiopathic or secondary to external
      stimuli, and is considered rare in tattoos. The infiltrate can be predominantly
      of B or T-cells, the latter being seldom reported in tattoos. We present a case
      of a predominantly T CLH, secondary to the black pigment of tattooing in a 35
      year-old patient, with a dense infiltrate of small, medium and scarce large T
      cells. Analysis of the rearrangement of T-cells receptor revealed a polyclonal
      proliferation. Since the infiltrate of CLH can simulate a T lymphoma, it is
      important to show that lesions from tattoos can have a predominance of T-cells. 

PMID- 25387519
TI  - Chronic ulcers: considerations about contaminant flora, infection and
      antimicrobial treatment.

PMID- 25387520
TI  - Chronic ulcers: considerations about contaminant flora, infection and
      antimicrobial treatment. Reply.

PMID- 25387521
TI  - On the necessity and biological significance of threshold-free regulon prediction
      outputs.
AB  - The in silico prediction of cis-acting elements in a genome is an efficient way
      to quickly obtain an overview of the biological processes controlled by a trans
      acting factor, and connections between regulatory networks. Several regulon
      prediction web tools are available, designed to identify DNA motifs predicted to
      be bound by transcription factors using position weight matrix-based algorithms.
      In this paper we expose and discuss the conflicting objectives of software
      creators (bioinformaticians) and software users (biologists), who aim for
      reliable and exhaustive prediction outputs, respectively. Software makers,
      concerned with providing tools that minimise the number of false positive hits,
      often impose a stringent threshold score for a sequence to be included in the
      list of the putative cis-acting sites. This rigidity eventually results in the
      identification of strongly reliable but largely straightforward sites, i.e. those
      associated with genes already anticipated to be targeted by the studied
      transcription factor. Importantly, this biased identification of strongly bound
      sequences contrasts with the biological reality where, in many circumstances, a
      weak DNA-protein interaction is required for the appropriate gene's expression.
      We show here a series of transcriptionally controlled systems involving weakly
      bound cis-acting elements that could never have been discovered because of the
      policy of preventing software users from modifying the screening parameters.
      Proposing only trustworthy prediction outputs thus prevents biologists from fully
      utilising their knowledge background and deciding to analyse statistically
      irrelevant hits that could nonetheless be potentially involved in subtle,
      unexpected, though essential cis-trans relationships. 

PMID- 25387522
TI  - An unexpected reaction of 2-alkynylaryldiazonium tetrafluoroborate with sulfur
      dioxide.
AB  - An unexpected result from the reaction of 2-alkynylaryldiazonium
      tetrafluoroborate with sulfur dioxide is described. In the presence of morpholin
      4-amine, this transformation catalyzed by copper(i) bromide proceeds through
      insertion of sulfur dioxide and intramolecular 5-endo cyclization, leading to
      benzo[b]thiophene 1,1-dioxides in moderate to good yields. 

PMID- 25387523
TI  - An assessment of the efficacy of searching in biomedical databases beyond MEDLINE
      in identifying studies for a systematic review on ward closures as an infection
      control intervention to control outbreaks.
AB  - BACKGROUND: The purpose of our study is to determine the value and efficacy of
      searching biomedical databases beyond MEDLINE for systematic reviews. METHODS: We
      analyzed the results from a systematic review conducted by the authors and others
      on ward closure as an infection control practice. Ovid MEDLINE including In
      Process & Other Non-Indexed Citations, Ovid Embase, CINAHL Plus, LILACS, and
      IndMED were systematically searched for articles of any study type discussing
      ward closure, as were bibliographies of selected articles and recent infection
      control conference abstracts. Search results were tracked, recorded, and analyzed
      using a relative recall method. The sensitivity of searching in each database was
      calculated. RESULTS: Two thousand ninety-five unique citations were identified
      and screened for inclusion in the systematic review: 2,060 from database
      searching and 35 from hand searching and other sources. Ninety-seven citations
      were included in the final review. MEDLINE and Embase searches each retrieved 80
      of the 97 articles included, only 4 articles from each database were unique. The
      CINAHL search retrieved 35 included articles, and 4 were unique. The IndMED and
      LILACS searches did not retrieve any included articles, although 75 of the
      included articles were indexed in LILACS. The true value of using regional
      databases, particularly LILACS, may lie with the ability to search in the
      language spoken in the region. Eight articles were found only through hand
      searching. CONCLUSIONS: Identifying studies for a systematic review where the
      research is observational is complex. The value each individual study contributes
      to the review cannot be accurately measured. Consequently, we could not determine
      the value of results found from searching beyond MEDLINE, Embase, and CINAHL with
      accuracy. However, hand searching for serendipitous retrieval remains an
      important aspect due to indexing and keyword challenges inherent in this
      literature.

PMID- 25387524
TI  - PP2A and Aurora differentially modify Cdc13 to promote telomerase release from
      telomeres at G2/M phase.
AB  - In yeast, the initiation of telomere replication at the late S phase involves in
      combined actions of kinases on Cdc13, the telomere binding protein. Cdc13
      recruits telomerase to telomeres through its interaction with Est1, a component
      of telomerase. However, how cells terminate the function of telomerase at G2/M is
      still elusive. Here we show that the protein phosphatase 2A (PP2A) subunit Pph22
      and the yeast Aurora kinase homologue Ipl1 coordinately inhibit telomerase at
      G2/M by dephosphorylating and phosphorylating the telomerase recruitment domain
      of Cdc13, respectively. While Pph22 removes Tel1/Mec1-mediated Cdc13
      phosphorylation to reduce Cdc13-Est1 interaction, Ipl1-dependent Cdc13
      phosphorylation elicits dissociation of Est1-TLC1, the template RNA component of
      telomerase. Failure of these regulations prevents telomerase from departing
      telomeres, causing perturbed telomere lengthening and prolonged M phase. Together
      our results demonstrate that differential and additive actions of PP2A and Aurora
      on Cdc13 limit telomerase action by removing active telomerase from telomeres at
      G2/M phase. 

PMID- 25387525
TI  - Further improvements to linear mixed models for genome-wide association studies.
AB  - We examine improvements to the linear mixed model (LMM) that better correct for
      population structure and family relatedness in genome-wide association studies
      (GWAS). LMMs rely on the estimation of a genetic similarity matrix (GSM), which
      encodes the pairwise similarity between every two individuals in a cohort. These
      similarities are estimated from single nucleotide polymorphisms (SNPs) or other
      genetic variants. Traditionally, all available SNPs are used to estimate the GSM.
      In empirical studies across a wide range of synthetic and real data, we find that
      modifications to this approach improve GWAS performance as measured by type I
      error control and power. Specifically, when only population structure is present,
      a GSM constructed from SNPs that well predict the phenotype in combination with
      principal components as covariates controls type I error and yields more power
      than the traditional LMM. In any setting, with or without population structure or
      family relatedness, a GSM consisting of a mixture of two component GSMs, one
      constructed from all SNPs and another constructed from SNPs that well predict the
      phenotype again controls type I error and yields more power than the traditional
      LMM. Software implementing these improvements and the experimental comparisons
      are available at http://microsoft.com/science. 

PMID- 25387526
TI  - Effective strategies for the management of pyoderma gangrenosum: a comprehensive
      review.
AB  - Pyoderma gangrenosum (PG) is an inflammatory disease characterized by painful
      skin ulcerations with undermined and erythematous borders. The etiology of PG is
      not well understood, but it is generally considered to be an aberrant immune
      response characterized by a dermal neutrophilc infiltrate. Given the existence of
      only a few PG clinical trials, treatment options are largely based upon anecdotal
      data and small case studies. In addition to classic immunosuppressive
      medications, PG has been reported to respond well to the anti-TNF agents,
      infliximab, etanercept, adalimumab. Newer biologics such as ustekinumab (anti-IL
      23), ixekizumab (anti-IL-17) and brodalumab (anti-IL-17R) are promising given the
      effect of IL-17 on neutrophil migration. However, the effectiveness of these
      newer agents remains to be rigorously evaluated. Multi-drug regimens have not
      been well described in the literature but are an excellent alternative for
      patients with refractory disease. Herein, we provide a comprehensive review of
      the pathophysiology of PG and of the different treatments available for managing
      PG patients, including the theoretical benefit of initiating multidrug regimens.
      We also provide one possible treatment algorithm for patients with refractory
      disease and give examples of refractory PG cases successfully treated with
      multidrug regimens.

PMID- 25387527
TI  - Mapping of a blood pressure QTL on chromosome 17 in American Indians of the
      strong heart family study.
AB  - BACKGROUND: Blood pressure (BP) is a complex trait, with a heritability of 30 to
      40%. Several genome wide associated BP loci explain only a small fraction of the
      phenotypic variation. Family studies can provide an important tool for gene
      discovery by utilizing trait and genetic transmission information among relative
      pairs. We have previously described a quantitative trait locus at chromosome
      17q25.3 influencing systolic BP in American Indians of the Strong Heart Family
      Study (SHFS). This locus has been reported to associate with variation in BP
      traits in family studies of Europeans, African Americans and Hispanics. METHODS:
      To follow-up persuasive linkage findings at this locus, we performed
      comprehensive genotyping in the 1-LOD unit support interval region surrounding
      this QTL using a multi-step strategy. We first genotyped 1,334 single nucleotide
      polymorphisms (SNPs) in 928 individuals from families that showed evidence of
      linkage for BP. We then genotyped a second panel of 306 SNPs in all SHFS
      participants (N = 3,807) for genes that displayed the strongest evidence of
      association in the region, and, in a third step, included additional genotyping
      to better cover the genes of interest and to interrogate plausible candidate
      genes in the region. RESULTS: Three genes had multiple SNPs marginally associated
      with systolic BP (TBC1D16, HRNBP3 and AZI1). In BQTN analysis, used to estimate
      the posterior probability that any variant in each gene had an effect on the
      phenotype, AZI1 showed the most prominent findings (posterior probability of
      0.66). Importantly, upon correction for multiple testing, none of our study
      findings could be distinguished from chance. CONCLUSION: Our findings demonstrate
      the difficulty of follow-up studies of linkage studies for complex traits,
      particularly in the context of low powered studies and rare variants underlying
      linkage peaks.

PMID- 25387528
TI  - C/EBP homologous protein (CHOP) contributes to hepatocyte death via the promotion
      of ERO1alpha signalling in acute liver failure.
AB  - CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) has been shown
      to be a key molecule in endoplasmic reticulum (ER) stress-mediated apoptosis. ER
      oxidoreductin 1-alpha (ERO1alpha), a target of CHOP, is an important oxidizing
      enzyme that regulates reactive oxygen species (ROS), which play a prominent role
      in hepatocellular death during acute liver failure (ALF). However, little is
      known about how CHOP facilitates ROS-induced hepatocellular injury. The present
      study was designed to investigate the roles and molecular mechanisms of CHOP in
      ALF. In the liver tissues from ALF patients, the expression of CHOP was
      significantly increased, which was accompanied by increased expression of dsRNA
      dependent protein kinase (PKR)-like ER kinase (PERK) signalling, activating
      transcription factor 4 (ATF6) signalling, inositol-requiring enzyme-1 (IRE1)
      signalling and ERO1alpha, as compared with healthy controls. In the mouse model
      of galactosamine (GaIN)/lipopolysaccharide (LPS)-induced ALF, the hepatocellular
      injury was accompanied by up-regulated PERK signalling, ATF6 signalling, IRE1
      signalling, CHOP and ERO1alpha. In contrast, CHOP deficiency decreased
      hepatocellular apoptosis/necrosis and increased animal survival. Furthermore,
      disruption of CHOP decreased ERO1alpha expression leading to reducing ROS-induced
      cell death in vivo and in vitro. Interestingly, ERO1alpha overexpression restored
      GaIN/LPS-induced hepatocellular injury in CHOP-deficient mice. Our studies
      demonstrate for the first time that CHOP promotes liver damage during ALF through
      activation of ERO1alpha, a key mediator to link ER stress and ROS. Therefore,
      targeting CHOP/ERO1alpha signalling could be a novel therapeutic approach during
      ALF. 

PMID- 25387529
TI  - Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid
      and their metabolism in the rat brain.
AB  - Chronic stress induces neurochemical changes that include neurotransmitter
      imbalance in the brain. Noise is an environmental factor inducing stress. Chronic
      noise stress affects monoamine neurotransmitter systems in the central nervous
      system. The effect on other excitatory and inhibitory neurotransmitter systems is
      not known. The aim was to study the role of chronic noise stress on the
      glutamatergic and gamma-aminobutyric acid (GABA)ergic systems of the brain.
      Female Wistar rats (155 +/- 5 g) were unintentionally exposed to noise due to
      construction (75-95 db, 3-4 hours/day, 5 days a week for 7-8 weeks) in the
      vicinity of the animal care facility. Glutamate/GABA levels and their metabolic
      enzymes were evaluated in different rat brain regions (cortex, hippocampus,
      striatum, and cerebellum) and compared with age and gender matched nonexposed
      rats. Chronic noise stress decreased glutamate levels and glutaminase activity
      27% and 33% in the cortex, 15% and 24% in the cerebellum. Glutamate levels
      increased 10% in the hippocampus, 28% in striatum and glutaminase activity 15% in
      striatum. Glutamine synthetase activity increased significantly in all brain
      regions studied, that is, cortex, hippocampus, striatum, and cerebellum (P <
      0.05). Noise stress-increased GABA levels and glutamate alpha decarboxylase
      activity 20% and 45% in the cortex, 13% and 28% in the hippocampus respectively.
      GABA levels and glutamate alpha decarboxylase activity decreased 15% and 14%,
      respectively in the striatum. GABA transaminase activity was significantly
      reduced in the cortex (55%), hippocampus (17%), and cerebellum (33%). Chronic
      noise stress differentially affected glutamatergic and GABAergic neurotransmitter
      systems in the rat brain, which may alter glutamate and GABA neurotransmission. 

PMID- 25387530
TI  - Influences of age, gender, and parents' educational level in knowledge, behavior
      and preferences regarding noise, from childhood to adolescence.
AB  - Exposure to loud sound during leisure activities for long periods of time is an
      important area to implement preventive health education, especially among young
      people. The aim was to identify the relations among awareness about the damaging
      effects of loud levels of sounds, previous exposures do loud sounds, preferences
      related to sound levels and knowledge about hearing protection with age, gender,
      and their parent's educational level among children. Prospective cross-sectional.
      Seven hundred and forty students (5-16 years old) and 610 parents participated in
      the study. Chi-square test, Fisher exact test and linear regression. About 86.5%
      of the children consider that loud sounds damage the ears and 53.7% dislike noisy
      places. Children were previously exposed to parties and concerts with loud music,
      Mardi Gras, firecrackers and loud music at home or in the car and loud music with
      earphones. About 18.4% of the younger children could select the volume of the
      music, versus 65.3% of the older ones. Children have poor information about
      hearing protection and do not have hearing protection device. Knowledge about the
      risks related to exposures to loud sounds and about strategies to protect their
      hearing increases with age, but preference for loud sounds and exposures to it
      increases too. Gender and parents' instructional level have little influence on
      the studied variables. Many of the children's recreational activities are noisy.
      It is possible that the tendency of increasing preference for loud sounds with
      age might be a result of a learned behavior. 

PMID- 25387531
TI  - Psychometric properties of the Bulgarian translation of noise sensitivity scale
      short form (NSS-SF): implementation in the field of noise control.
AB  - The Noise Sensitivity Scale Short Form (NSS-SF), developed in English as a more
      practical form of the classical Weinstein NSS, has not to date been validated in
      other cultures, and its validity and reliability have not yet been confirmed.
      This study aimed to validate NSS-SF in Bulgarian and to demonstrate its
      applicability. The study comprised test-retest (n = 115) and a field-testing (n =
      71) of the newly validated scale. Its construct validity was examined with
      confirmatory factor analysis, and very good model-fit was observed. Temporal
      stability was assessed in a test-retest (r = 0.990), convergent validity was
      examined with single-item susceptibility to the noise scale (r = 0.906) and
      discriminant validity was confirmed with single-item noise annoyance scale (r =
      0.718). The lowest observed McDonald's omega across the studies was 0.923. The
      cross-cultural validation of NSS-SF was successful but it proved to be somewhat
      problematic with respect to its annoyance-based items. 

PMID- 25387532
TI  - Noise in restaurants: levels and mathematical model.
AB  - Noise affects the dining atmosphere and is an occupational hazard to restaurant
      service employees worldwide. This paper examines the levels of noise in dining
      areas during peak hours in different types of restaurants in Hong Kong SAR,
      China. A mathematical model that describes the noise level in a restaurant is
      presented. The 1-h equivalent continuous noise level (L(eq,1-h)) was measured
      using a Type-1 precision integral sound level meter while the occupancy density,
      the floor area of the dining area, and the ceiling height of each of the surveyed
      restaurants were recorded. It was found that the measured noise levels using
      Leq,1-h ranged from 67.6 to 79.3 dBA in Chinese restaurants, from 69.1 to 79.1
      dBA in fast food restaurants, and from 66.7 to 82.6 dBA in Western restaurants.
      Results of the analysis of variance show that there were no significant
      differences between means of the measured noise levels among different types of
      restaurants. A stepwise multiple regression analysis was employed to determine
      the relationships between geometrical and operational parameters and the measured
      noise levels. Results of the regression analysis show that the measured noise
      levels depended on the levels of occupancy density only. By reconciling the
      measured noise levels and the mathematical model, it was found that people in
      restaurants increased their voice levels when the occupancy density increased.
      Nevertheless, the maximum measured hourly noise level indicated that the noise
      exposure experienced by restaurant service employees was below the regulated
      daily noise exposure value level of 85 dBA.

PMID- 25387533
TI  - Burden of myocardial infarction attributable to road-traffic noise: a pilot study
      in Belgrade.
AB  - The aim of this pilot study was to calculate the disability-adjusted life years
      (DALY) as a quantification of the burden of myocardial infarction (MI)
      attributable to road-traffic noise in Belgrade, Serbia. Exposure to road-traffic
      noise was estimated on a sample of almost 6000 adult inhabitants living in the
      central municipality Stari Grad in Belgrade, Serbia. Each participant was
      assigned to daytime noise levels for 16 h exposure measured on the street of
      current residence. Population-attributable fraction of MI due to road-traffic
      noise was calculated based on the distribution of the population in different
      noise exposure categories and the respective relative risk of MI compared to the
      reference level. DALYs due to noise-related MI were calculated as the sum of
      years of life lost and years with disability. The contribution of road traffic
      noise to the occurrence of MI for the population of the municipality Stari Grad
      in Belgrade equals 2.518%. Total DALY for MI due to road-traffic noise results in
      176 years, that is, 115 years for men and 61 years for women. When adjusted for
      the present size of the population in Belgrade, total DALY due to road-traffic
      noise equals 107 years/million inhabitants that is, 70/million inhabitants for
      men and 37/million inhabitants for women. The burden of disease due to road
      traffic noise in Belgrade is relatively small but noteworthy from the public
      health point of view. 

PMID- 25387534
TI  - Characterizing urban areas with good sound quality: development of a research
      protocol.
AB  - Due to rapid urbanization, the spatial variation between wanted and unwanted
      sounds will decrease or even disappear. Consequently, the characteristics of
      (urban) areas where people can temporarily withdraw themselves from urban
      stressors such as noise may change or become increasingly scarce. Hardly any
      research has been carried out into the positive health effects of spending time
      in areas with a good sound quality. One of the problems is that an overview of
      what aspects determines good sound quality in urban areas and how these are
      interrelated is lacking. This paper reviews the literature pertaining to the
      sound quality of urban areas. Aim is to summarize what is known about the
      influence of social, spatial, and physical aspects other than sounds, on peoples'
      perception of urban sound qualities. Literature from both conventional sound
      research and from the so-called soundscape field, published between 2000 and the
      beginning of 2013 in English or Dutch, was evaluated. Although a general set of
      validated indicators that can be directly applied, is not available yet, a set of
      indicators was derived from the literature. These form the basis of a study
      protocol that will be applied in "Towards a Sustainable acoustic Environment", a
      project that aims to describe sound qualities at a low-scale level. Key-elements
      of this study protocol, including a questionnaire and the systematic audit of
      neighborhoods, were presented in this paper. 

PMID- 25387535
TI  - Railway noise annoyance: exposure-response relationships and testing a
      theoretical model by structural equation analysis.
AB  - In some regions the exposure to railway noise is extremely concentrated, which
      may lead to high residential annoyance. Nonacoustical factors contribute to these
      reactions, but there is limited evidence on the interrelations between the
      nonacoustical factors that influence railway noise annoyance. The aims of the
      present study were (1) to examine exposure-response relationships between long
      term railway noise exposure and annoyance in a region severely affected by
      railway noise and (2) to determine a priori proposed interrelations between
      nonacoustical factors by structural equation analysis. Residents (n = 320) living
      close to railway tracks in the Middle Rhine Valley completed a socio-acoustic
      survey. Individual noise exposure levels were calculated by an acoustical
      simulation model for this area. The derived exposure-response relationships
      indicated considerably higher annoyance at the same noise exposure level than
      would have been predicted by the European Union standard curve, particularly for
      the night-time period. In the structural equation analysis, 72% of the variance
      in noise annoyance was explained by the noise exposure (L(den)) and nonacoustical
      variables. The model provides insights into several causal mechanisms underlying
      the formation of railway noise annoyance considering indirect and reciprocal
      effects. The concern about harmful effects of railway noise and railway traffic,
      the perceived control and coping capacity, and the individual noise sensitivity
      were the most important factors that influence noise annoyance. All effects of
      the nonacoustical factors on annoyance were mediated by the perceived control and
      coping capacity and additionally proposed indirect effects of the theoretical
      model were supported by the data.

PMID- 25387536
TI  - Noise exposure immediately activates cochlear mitogen-activated protein kinase
      signaling.
AB  - Noise-induced hearing loss (NIHL) is a major public health issue worldwide.
      Uncovering the early molecular events associated with NIHL would reveal
      mechanisms leading to the hearing loss. Our aim is to investigate the immediate
      molecular responses after different levels of noise exposure and identify the
      common and distinct pathways that mediate NIHL. Previous work showed mice exposed
      to 116 decibels sound pressure level (dB SPL) broadband noise for 1 h had greater
      threshold shifts than the mice exposed to 110 dB SPL broadband noise, hence we
      used these two noise levels in this study. Groups of 4-8-week-old CBA/CaJ mice
      were exposed to no noise (control) or to broadband noise for 1 h, followed by
      transcriptome analysis of total cochlear RNA isolated immediately after noise
      exposure. Previously identified and novel genes were found in all data sets.
      Following exposure to noise at 116 dB SPL, the earliest responses included up
      regulation of 243 genes and down-regulation of 61 genes, while a similar exposure
      at 110 dB SPL up-regulated 155 genes and down-regulated 221 genes. Bioinformatics
      analysis indicated that mitogen-activated protein kinase (MAPK) signaling was the
      major pathway in both levels of noise exposure. Nevertheless, both qualitative
      and quantitative differences were noticed in some MAPK signaling genes, after
      exposure to different noise levels. Cacna1b , Cacna1g , and Pla2g6 , related to
      calcium signaling were down-regulated after 110 dB SPL exposure, while the fold
      increase in the expression of Fos was relatively lower than what was observed
      after 116 dB SPL exposure. These subtle variations provide insight on the factors
      that may contribute to the differences in NIHL despite the activation of a common
      pathway. 

PMID- 25387537
TI  - A comparison of the effects of solvent and noise exposure on hearing, together
      and separately.
AB  - The objective of the present study was to assess the effects of occupational
      exposure to noise and organic solvents on hearing loss in bus and truck plant
      workers. Our case control study contained 469 workers from a bus and truck plant
      divided into three groups. The first group contained workers exposed to only
      noise; the second group contained workers exposed to both noise and mixture
      solvents at a permissible level; and the third group included workers exposed to
      permissible levels of solvents. The control group (Group 4) included 119
      individuals selected randomly, persons who were not exposed to noise and
      solvents. These groups were compared in terms of each individual's frequency
      hearing loss in both ears. Our study demonstrates that combined exposure to mixed
      solvents and noise can exacerbate hearing loss in workers. Hence, a suitable
      hearing protection program is advised that would contain short-interval
      audiometric examinations and efficient hearing protectors. 

PMID- 25387538
TI  - Morphological changes of adrenal gland and heart tissue after varying duration of
      noise exposure in adult rat.
AB  - Noise was considered an environmental stressor causing a wide range of health
      effects such as acoustic, cardiovascular, nervous, and endocrine systems. The
      present study was performed to examine the effects of a repeated noise exposure
      on adrenal gland and heart tissue. The results showed that exposure to moderate
      intensity sound (70 dB[A]) causes time-dependent changes in the morphological
      structure of the adrenal cortex that involve disarrangement of cells and
      modification in thickness of the different layers of the adrenal gland. The
      experiment revealed important changes depending on exposure duration in the
      morphological structure of heart tissue that causes irreversible cell damage
      leading to cell death or necrosis. 

PMID- 25387539
TI  - Stapedial reflex and recruitment: what is the relationship with tinnitus?
AB  - Tinnitus is characterized by an auditory perception of sound, with no stimuli
      from the external environment. Tinnitus is an increasingly significant complaint,
      affecting 10-17% of the world population. As a symptom, it should always be
      considered with pathology in the auditory system. Our study aims to assess the
      relationship of this symptom with the presence of a stapedial reflex and the
      phenomenon of recruitment. Medical records of patients complaining of subjective
      tinnitus during their first consultation in the Outpatient Clinic of the Unicamp
      Teaching Hospital, in Brazil, between 2011 and 2012 were analyzed. We carried out
      a study with 65 non-randomized tinnitus individuals using questionnaires,
      clinical and audiological evaluations. The visual analogue scale was used to
      characterize the degree of disturbance caused by tinnitus. Statistical tests were
      performed using the IBM SPSS Statistics 19. No association was found between
      tinnitus and the presence of acoustic reflex or phenomenon of recruitment. We
      concluded that there is no relationship between tinnitus, the phenomenon of
      recruitment or the presence of an acoustic reflex. 

PMID- 25387540
TI  - A vision of the environmental and occupational noise pollution in Malaysia.
AB  - Environmental noise remains a complex and fragmented interplay between
      industrialization, population growth, technological developments, and the living
      environment. Next to the circulatory diseases and cancer, noise pollution has
      been cited as the third epidemic cause of psychological and physiological
      disorders internationally. A reliable and firm relationship between the
      cumulative health implications with the traffic annoyance and occupational noise
      has been established. This agenda has called for an integrated, coordinated, and
      participatory approach to the reliable protection of noise interference. Despite
      several fragmented policies, legislation and global efforts have been addressed;
      the noise pollution complaints have been traditionally neglected in developing
      countries, especially in Malaysia. This paper was undertaken to postulate an
      initial platform to address the dynamic pressures, gigantic challenges, and
      tremendous impacts of noise pollution scenario in Malaysia. The emphasis is
      speculated on the traffic interference and assessment of industrial and
      occupational noise. The fundamental importance of noise monitoring and modeling
      is proposed. Additionally, the confronting conservation program and control
      measure for noise pollution control are laconically elucidated. 

PMID- 25387541
TI  - Open questions in the treatment of cancer pain: time for a strong evidence-based
      approach?
AB  - Pain affects patients with cancer at any stage of their disease. Yet, it is not
      adequately treated in a significant percentage of cases. In 1986, the WHO
      proposed a three-step approach for the treatment of pain in cancer patients (from
      nonopioids to weak opioids to strong opioids, according to pain intensity)
      following the recommendations of an international group of experts. The
      application of the WHO strategy demonstrated that a clear and simple approach is
      of educational value and ensured worldwide dissemination. However, there is
      little evidence that the WHO approach is the best, and there are still several
      points to debate on the treatment of cancer pain. 

PMID- 25387543
TI  - Integration of energy analytics and smart energy microgrid into mobile medicine
      operations for the 2012 Democratic National Convention.
AB  - INTRODUCTION: Disasters create major strain on energy infrastructure in affected
      communities. Advances in microgrid technology offer the potential to improve "off
      grid" mobile disaster medical response capabilities beyond traditional diesel
      generation. The Carolinas Medical Center's mobile emergency medical unit (MED-1)
      Green Project (M1G) is a multi-phase project designed to demonstrate the benefits
      of integrating distributive generation (DG), high-efficiency batteries, and
      "smart" energy utilization in support of major out-of-hospital medical response
      operations. METHODS: Carolinas MED-1 is a mobile medical facility composed of a
      fleet of vehicles and trailers that provides comprehensive medical care
      capacities to support disaster response and special-event operations. The M1G
      project partnered with local energy companies to deploy energy analytics and an
      energy microgrid in support of mobile clinical operations for the 2012 Democratic
      National Convention (DNC) in Charlotte, North Carolina (USA). Energy use data
      recorded throughout the DNC were analyzed to create energy utilization models
      that integrate advanced battery technology, solar photovoltaic (PV), and energy
      conservation measures (ECM) to improve future disaster response operations.
      RESULTS: The generators that supply power for MED-1 have a minimum loading ratio
      (MLR) of 30 kVA. This means that loads below 30 kW lead to diesel fuel
      consumption at the same rate as a 30 kW load. Data gathered from the two DNC
      training and support deployments showed the maximum load of MED-1 to be around 20
      kW. This discrepancy in MLR versus actual load leads to significant energy waste.
      The lack of an energy storage system reduces generator efficiency and limits
      integration of alternative energy generation strategies. A storage system would
      also allow for alternative generation sources, such as PV, to be incorporated.
      Modeling with a 450 kWh battery bank and 13.5 kW PV array showed a 2-fold
      increase in potential deployment times using the same amount of fuel versus the
      current conventional system. CONCLUSIONS: The M1G Project demonstrated that the
      incorporation of a microgrid energy management system and a modern battery system
      maximize the MED-1 generators' output. Using a 450 kWh battery bank and 13.5 kW
      PV array, deployment operations time could be more than doubled before refueling.
      This marks a dramatic increase in patient care capabilities and has significant
      public health implications. The results highlight the value of smart-microgrid
      technology in developing energy independent mobile medical capabilities and
      expanding cost-effective, high-quality medical response.

PMID- 25387542
TI  - Strongyle infections and parasitic control strategies in German horses - a risk
      assessment.
AB  - BACKGROUND: As a consequence of the increasing levels of anthelmintic resistance
      in cyathostomes, new strategies for equine parasite control are being
      implemented. To assess the potential risks of these, the occurrence of strongyles
      was evaluated in a group of 1887 horses. The distribution of fecal egg counts
      (FECs), the frequency of anthelmintic drug use, and the deworming intervals were
      also analyzed. Between June 2012 and May 2013, 1887 fecal samples from either
      selectively or strategically dewormed horses were collected at 195 horse farms
      all over Germany and analyzed quantitatively with a modified McMaster technique.
      All samples with FEC >=20 eggs per gram (EPG) were subjected to coproculture to
      generate third-stage larvae (LIII) for species differentiation. RESULTS: Egg
      counts were below the limit of detection (20 EPG) in 1046 (55.4%) samples and
      above it in 841 (44.6%) samples. Strongylus vulgaris larvae were identified in
      two of the 841 positive samples. Infections with cyathostomes were found on every
      farm. The most frequently applied anthelmintic was ivermectin (788/50.8%),
      followed by pyrantel (336/21.6%). The mean time since last treatment was 6.3
      months. High-egg-shedding (>500 EPG) strategically dewormed horses (183/1357)
      were treated, on average, three times/year. The planned treatment date was
      already exceeded by 72.5% of the high egg-shedders and by 58.1% of the moderate
      (200-500 EPG) and low egg-shedders (20-199 EPG). CONCLUSIONS: S. vulgaris seems
      to be rare in Germany and no difference in its frequency has yet been found
      between selectively treated horses and horses receiving treatment in strategic
      intervals. However, inconsistent parasite control has been observed. Therefore,
      to minimize the risks for disease, consistent and efficient parasite control
      should be implemented.

PMID- 25387544
TI  - Predictive supracolloidal helices from patchy particles.
AB  - A priori prediction of supracolloidal architectures from nanoparticle and
      colloidal assembly is a challenging goal in materials chemistry and physics.
      Despite intense research in this area, much less has been known about the
      predictive science of supracolloidal helices from designed building blocks.
      Therefore, developing conceptually new rules to construct supracolloidal
      architectures with predictive helicity is becoming an important and urgent task
      of great scientific interest. Here, inspired by biological helices, we show that
      the rational design of patchy arrangement and interaction can drive patchy
      particles to self-assemble into biomolecular mimetic supracolloidal helices. We
      further derive a facile design rule for encoding the target supracolloidal
      helices, thus opening the doors to the predictive science of these supracolloidal
      architectures. It is also found that kinetics and reaction pathway during the
      formation of supracolloidal helices offer a unique way to study supramolecular
      polymerization, and that well-controlled supracolloidal helices can exhibit
      tailorable circular dichroism effects at visible wavelengths. 

PMID- 25387545
TI  - Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab
      Treatment.
AB  - Neuromyelitis optica is an autoimmune disease characterized by acute episodes of
      transverse myelitis and optic neuritis. Several small, open-label studies suggest
      rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis
      optica; however, there is little consensus on timing or duration of treatment.
      Here we report four patients with severe relapsing neuromyelitis optica who were
      stabilized on rituximab and, after discontinuing treatment, continued to
      experience prolonged remission of their disease. Remission ranged from 4.5 to
      10.5 years total, including 3 to 9 years off all therapies. The patients had
      sustained clinical responses despite normal B-lymphocyte levels and, in at least
      2 patients, continued seropositivity for aquaporin-4 antibodies. These cases
      suggest that rituximab may induce prolonged remission in certain neuromyelitis
      optica patients, and they highlight the need for further elucidation of
      rituximab's mechanism in neuromyelitis optica. 

PMID- 25387546
TI  - Hemichorea-Hemiballismus as the First Sign of Type 1b Diabetes During Adolescence
      and Its Recurrence in the Setting of Infection.
AB  - Chorea may be secondary to hyperosmolar nonketotic hyperglycemia, but such
      situation has rarely been described in adolescents, particularly as the initial
      and single manifestation of type 1 diabetes. We describe a case of a previously
      healthy 14-year-old girl with sudden onset of choreic movements on her left upper
      and lower limbs. Brain computed tomography (CT) and magnetic resonance imaging
      (MRI) revealed an area of hyperdensity/hyperintensity affecting the right
      striatum. Blood glucose was 349 mg/dL. Despite adequate glucose control, the
      involuntary movements persisted and haloperidol, later substituted with
      valproate, was prescribed, with satisfactory but not complete resolution of the
      chorea. In 2 other occasions, when the patient had an infection and subsequent
      hyperglycemia, the chorea relapsed. Although not common, hyperglycemia must be
      considered in the differential diagnosis of acute hemichorea-hemiballismus in
      children and adolescents, particularly because it is a potentially reversible
      cause. 

PMID- 25387547
TI  - Does an Increased Prevalence Rate of Attention-Deficit Hyperactivity Disorder
      (ADHD) Exist Among Persons With Albinism?

PMID- 25387548
TI  - Risk Factors for Acute Symptomatic Seizure in Bacterial Meningitis in Children.
AB  - The aim of this study was to investigate the association between clinical and
      laboratory parameters at admission and the occurrence of in-hospital symptomatic
      seizures in children with acute bacterial meningitis in Brazil. A retrospective
      case-control study in 270 children with confirmed bacterial meningitis, aged from
      1 month to 14 years, was conducted between January 2004 and December 2008.
      Associations with the occurrence of in-hospital epileptic seizures were adjusted
      using stepwise multiple logistic regression analysis. Sixty-seven children
      suffered at least one in-hospital epileptic seizure. After multivariate analysis,
      the independent predictors considered for in-hospital epileptic seizures were as
      follows: age less than 2 years (odds ratio = 0.97; 95% confidence interval 0.97
      0.98), pneumococcal etiology (odds ratio = 4.55; 95% confidence interval 1.88
      11.0); altered mental status (odds ratio = 3.47; 95% confidence interval 1.66
      7.26) and cerebrospinal fluid leukocyte count below 1000 cells (odds ratio =
      2.14; 95% confidence interval 0.99-4.60). Mortality was higher in patients with
      intrahospital epileptic seizures compared to those without (25/67 [37.3%] vs
      9/203 [4.43%], P < .001]. 

PMID- 25387550
TI  - The new hepatitis C era: the guidelines are now available, reimbursement not
      yet...

PMID- 25387549
TI  - Association between single nucleotide polymorphism of IL15RA gene with
      susceptibility to ossification of the posterior longitudinal ligament of the
      spine.
AB  - BACKGROUND: Previous studies reported the association between single nucleotide
      polymorphism (SNP) of IL15 receptor alpha (IL15RA) gene with susceptibility to
      ossification of the posterior longitudinal ligament of the spine (OPLL). However,
      the results were still in controversy. Therefore, the purpose of the present
      study was to investigate the association between SNPs of IL15RA gene with
      susceptibility to OPLL in a Chinese Han population. METHODS: A total of 235 OPLL
      patients and 250 age-matched healthy controls were recruited. All the subjects
      were genotyped using the PCR (polymerase chain reaction)-based invader assay. A
      case-control study was performed to define the contribution of rs2228059 and
      rs2296139 to predisposition of OPLL. We also performed subgroup analysis
      according to the different gender. RESULTS: A significant association of
      rs2228059 with OPLL was observed in the Chinese Han population (p <0.001, OR =
      1.63, 95% CI = 1.26-2.11). The subgroup analysis showed that there was a
      significant association between the allele frequency of rs2228059 and the
      susceptibility of OPLL in males (p = 0.002, OR = 1.72, 95% CI = 1.23-2.42).
      However, there was no significant association between SNP of rs2296139 and
      susceptibility to OPLL. CONCLUSIONS: The present study demonstrates that the SNP
      of rs2228059 in IL15RA gene is associated with susceptibility to OPLL in a
      Chinese Han population, especially in males.

PMID- 25387551
TI  - Dutch guidance for the treatment of chronic hepatitis C virus infection in a new
      therapeutic era.
AB  - BACKGROUND: A new era for the treatment of chronic hepatitis C is about to
      transpire. With the introduction of the first-generation protease inhibitors the
      efficacy of hepatitis C treatment improved significantly. Since then, the
      therapeutic agenda has moved further forward with the recent approval of
      sofosbuvir and the expected approval of agents such as simeprevir and
      daclatasvir. This paper, developed parallel to the approval of sofosbuvir, is to
      serve as a guidance for the therapeutic management of chronic hepatitis C.
      METHODS: We performed a formal search through PubMed, Web of Science and
      ClinicalTrials.gov to identify all clinical trials that have been conducted with
      EMA-approved new agents in hepatitis C; for this version (April 2014) we focused
      on sofosbuvir. For each disease category, the evidence was reviewed and
      recommendations are based on GRADE. RESULTS: We identified 11 clinical trials
      with sofosbuvir and for each disease category recommendations for treatment are
      made. Not all disease categories were studied extensively and therefore in some
      cases we were unable to provide recommendations. CONCLUSION: The recent approval
      of sofosbuvir will most likely change the therapeutic landscape of chronic
      hepatitis C. The use of sofosbuvir-containing regimens can shorten the duration
      of therapy, increase efficacy and result in less side effects, compared with
      standard of care. The efficacy relative to standard of care needs to be weighed
      against the increased costs of sofosbuvir. With future approval of the other
      direct-acting antivirals, the outcome of hepatitis C treatment will likely
      improve further and this guidance will be updated.

PMID- 25387552
TI  - To treat or not to treat: developments in the field of advanced differentiated
      thyroid cancer.
AB  - BACKGROUND: Thyroid cancer is the most prevalent endocrine malignancy. Based on
      the increased understanding of thyroid tumourigenesis, novel therapeutic agents
      have been identified. However, given the low incidence, the good prognosis of the
      majority of these tumours and the limited evidence of different treatment
      modalities, a wide variety of treatment strategies are available. These are
      mostly based on small studies, data from retrospective analyses and the
      particular experiences of treating physicians. We discuss the recent developments
      in the treatment of advanced differentiated thyroid cancer. CASE DESCRIPTION:
      Three cases demonstrate the considerations involved in treatment decisions for
      patients with advanced thyroid cancer. The first patient achieved stable disease
      for over five years with different targeted therapies. The second patient shows
      the potential (severe) toxicity of these drugs and the third patient illustrates
      the indolent nature of this disease. CONCLUSION: The treatment of patients with
      extensively metastasised thyroid cancer is very complicated. The timing of
      initiation of therapy and the potential toxicity of targeted therapies are
      important in the clinical decision to treat or not to treat because of the slowly
      progressive course of differentiated thyroid cancer. When targeted therapy is
      considered, it remains of great importance to enrol patients in clinical studies
      in order to further determine the position of these therapies, to develop more
      effective (combination) treatment schemes, and above all, to identify those
      patients that truly benefit.

PMID- 25387553
TI  - IP-10 in chronic hepatitis C patients treated with high-dose interferon.
AB  - INTRODUCTION: Interferon-g-inducible protein-10 (IP-10) serum levels are
      associated with IL28B genotype and may predict response to interferon/ribavirin
      based therapy in chronic hepatitis C patients. Our aim was to relate IP-10 levels
      before and during treatment to treatment outcome, viral HCV-RNA kinetics and
      IL28B genotype. PATIENTS AND METHODS: A cohort of chronic hepatitis C patients
      was treated with high-dose interferon for six weeks, followed by standard
      peginterferon/ ribavirin for 24 or 48 weeks. IP-10 and HCV-RNA levels were
      frequently determined before, during and after treatment. RESULTS: IP-10 levels
      increased from log2.56 pg/ml at baseline to log3.48 pg/ml at Day 1 and gradually
      diminished thereafter. IP-10 levels at any time point were not statistically
      different between patients with or without sustained viral response (SVR).
      Patients with IL28B CC genotype had significantly lower baseline IP-10 levels (p
      = 0.019) and a higher increase of IP-10 levels from baseline to Day 1 than
      patients with IL28B non-CC genotypes (p = 0.015). Patients with HCV-RNA decline
      &#8805; 2.28log10 at Day 1 had significantly lower baseline IP-10 levels (p =
      0.016) and a higher increase of IP-10 levels from baseline to Day1 (p = 0.047)
      than patients with HCV-RNA decline of < 2.28log10 at Day 1. CONCLUSIONS: In
      patients treated with high induction dose interferon, IP-10 levels at any time
      point were not predictive for SVR. Low baseline IP-10 levels and a higher
      increase of IP-10 levels from baseline to Day 1 were associated with IL28B CC
      genotype and HCV-RNA decline &#8805; 2.28log10 at Day 1. This suggests that, in
      our cohort, for prediction of SVR the added value of IP-10 to IL28B genotype and
      early viral kinetics is limited.

PMID- 25387554
TI  - Determinants of health-related quality of life in older patients after acute
      hospitalisation.
AB  - BACKGROUND: To assess the association between demographics, comorbidity,
      geriatric conditions, and three health-related quality of life (HRQOL) outcomes
      one year after acute hospitalisation in older patients. METHODS: A prospective
      cohort study conducted between 2006 and 2009 with one-year follow-up in 11
      medical wards at two university hospitals and one teaching hospital in the
      Netherlands. Participants were 473 patients of 65 years and older, acutely
      hospitalised for more than 48 hours. Demographics, Charlson Comorbidity Index
      (CCI), and data on 18 geriatric conditions were collected at baseline. At
      baseline and 12 months post-admission, the EuroQol-5D was administered. Based on
      a population-derived valuation (Dutch EuroQol-5D tariff), utilities (range -0.38
      1.00) were determined, which were used to calculate quality-adjusted life years
      (QALY) over one year (max QALY score 1). The EuroQol-5D visual analogue scale
      (VAS) (range 0-100) was also used. Linear regression analyses were performed to
      explore the association between the independent variables and the three HRQOL
      outcomes. RESULTS: CCI was most consistently significantly associated with HRQOL
      outcomes: Beta -0.05 (95% CI -0.06--0.03) for utility, -0.04 (95% CI -0.05-0.03)
      for QALY, -1.03 (95% CI -2.06-0.00) for VAS, p < 0.001, < 0.001, 0.05,
      respectively). Baseline utility was significantly associated with one-year
      utility (beta 0.25, 95% CI 0.11-0.39, p < 0.01) and QALY (beta 0.31, 95% CI 0.17
      0.45, p < 0.001). The number of geriatric conditions at baseline was more
      strongly associated with one-year utility than any individual geriatric
      condition. CONCLUSION: Less comorbidity, better utility and less geriatric
      conditions at baseline were associated with better HRQOL one year after acute
      hospitalisation in older patients.

PMID- 25387555
TI  - An African woman with pulmonary cavities: TB or not TB?
AB  - Cavitary lung lesions in patients from developing countries are mostly caused by
      tuberculosis (TB). However, when TB cannot be confirmed, a primary lung abscess
      caused by anaerobic bacteria from the mouth should be considered, especially in
      patients with poor dentition. We present a case of a Sudanese woman with a
      cavitary lung lesion and severe gingivitis. Bulleidia extructa was isolated as a
      single pathogen from the pulmonary cavity. 

PMID- 25387556
TI  - A rare cause of haematuria.

PMID- 25387557
TI  - A young man with intermittent abdominal pain and anaemia: a peculiar finding.

PMID- 25387558
TI  - A lung cancer patient with painful fingers.

PMID- 25387559
TI  - A 41-year-old man with an increased abdominal girth.

PMID- 25387560
TI  - When to treat paracetamol overdose.

PMID- 25387561
TI  - Estimating productivity costs using the friction cost approach in practice: a
      systematic review.
AB  - INTRODUCTION: The choice of the most appropriate approach to valuing productivity
      loss has received much debate in the literature. The friction cost approach has
      been proposed as a more appropriate alternative to the human capital approach
      when valuing productivity loss, although its application remains limited. This
      study reviews application of the friction cost approach in health economic
      studies and examines how its use varies in practice across different country
      settings. METHODS: A systematic review was performed to identify economic
      evaluation studies that have estimated productivity costs using the friction cost
      approach and published in English from 1996 to 2013. A standard template was
      developed and used to extract information from studies meeting the inclusion
      criteria. RESULTS: The search yielded 46 studies from 12 countries. Of these, 28
      were from the Netherlands. Thirty-five studies reported the length of friction
      period used, with only 16 stating explicitly the source of the friction period.
      Nine studies reported the elasticity correction factor used. The reported
      friction cost approach methods used to derive productivity costs varied in
      quality across studies from different countries. CONCLUSIONS: Few health economic
      studies have estimated productivity costs using the friction cost approach. The
      estimation and reporting of productivity costs using this method appears to
      differ in quality by country. The review reveals gaps and lack of clarity in
      reporting of methods for friction cost evaluation. Generating reporting
      guidelines and country-specific parameters for the friction cost approach is
      recommended if increased application and accuracy of the method is to be
      realized.

PMID- 25387562
TI  - Evolution of the NBOMes: 25C- and 25B- Sold as 25I-NBOMe.
AB  - INTRODUCTION: The NBOMes (N-benzyl-oxy-methyl derivatives of known 2C
      phenylethylamines) are a new and growing class of potent synthetic stimulants.
      Case reports provide the bulk of available safety and clinical data for
      clinicians. We report two cases of NBOMe intoxication with 25C-NBOMe (the first
      lab-confirmed US case) and 25B-NBOMe, respectively, both confirmed via triple
      quadrapole mass spectrometry. CASE REPORTS: Case 1: A 16-year-old girl had a
      generalized seizure after reported use of 25I-NBOMe. She presented with altered
      mental status, lower extremity rigidity, and elevated CPK (6042 U/L). Despite
      treatment with benzodiazepines, her lower extremity rigidity persisted and CPK
      peaked at 47,906 U/L. She was discharged on hospital day 8. Serum and urine
      specimens confirmed presence of 25C-NBOMe. Case 2: A 15-year-old boy developed
      bizarre behavior after reported use of 25I-NBOMe. In the ED, he had two
      generalized seizures and persistent muscle rigidity. CPK peaked at 429 U/L.
      Seizures were managed with benzodiazepines, and he was discharged within 24 h.
      Serum specimens revealed 25B-NBOMe. DISCUSSION: NBOMes are amphetamine
      derivatives and highly potent 5-HT(2A) receptor agonists. Clinical manifestations
      are a product of enhanced central sympathetic and serotonergic tone. We report
      two cases of NBOMe intoxication in patients who believed they used 25I-NBOME,
      while lab confirmation proved otherwise. Whether unique clinical manifestations
      are specific to the NBOMe variant, dose, route of administration, or other
      factors is unknown. Laboratory confirmation may play a role in identifying
      unexpected NBOMe variants, while contributing to the epidemiologic data on these
      novel substances.

PMID- 25387565
TI  - Biomarkers to assess the efficiency of treatment with platinum-based drugs: what
      can metallomics add?
AB  - Since the approval of cisplatin as an antineoplastic drug, the medical and the
      scientific communities have been concerned about the side effects of platinum
      based drugs, and this has been the dose-limiting factor that leads to reduced
      treatment efficiency. Another important issue is the intrinsic or acquired
      resistance of some patients to treatment. Identifying proper biomarkers is
      crucial in evaluating the efficiency of a treatment, assisting physicians in
      determining, at early stages, whether or not the patient presents resistance to
      the drug, minimizing severe side effects, and allowing them to redirect the
      established course of chemotherapy. A great effort is being made to identify
      biomarkers that can be used to predict the outcome of the treatment of cancer
      patients with platinum-based drugs. In this context, the metallomic approach has
      not yet been used to its full potential. Since the basis of these drugs is
      platinum, the monitoring of biomarkers containing this metal should be the
      natural approach to evaluate treatment progress. This review intends to show
      where the research in this field stands and points out some gaps that can be
      filled by metallomics. 

PMID- 25387566
TI  - Analysis of regulatory T cells frequency in peripheral blood and tumor tissues in
      papillary thyroid carcinoma with and without Hashimoto's thyroiditis.
AB  - PURPOSE: Regulatory T cells (Treg) suppress the immune reaction. The aim of the
      present study was to investigate the clinicopathologic significance and roles of
      Treg in papillary thyroid carcinoma (PTC) patients with and without Hashimoto's
      thyroiditis. METHODS: Flow cytometry was used to detect the percentage of
      CD4+CD25+CD127low/- Treg among CD4+ T cells in peripheral blood. FoxP3+ Treg were
      detected by immunohistochemistry in the tumor tissues. RESULTS: The percentage of
      CD4+CD25+CD127low/- Treg among CD4+ T cells was significantly higher in PTC
      patients than that in multinodular goiter (MNG) patients. There were large
      numbers of tumor-infiltrating FoxP3+ Treg in primary PTC and metastatic lymph
      nodes tissues; however, there was no FoxP3 expression in the MNG tissues. Higher
      percentage of Treg both in peripheral blood and tumor tissues was associated with
      extrathyroidal extension and lymph nodes metastasis. The percentage of
      CD4+CD25+CD127low/- Treg among CD4+ T cells in peripheral blood of PTC patients
      with Hashimoto's thyroiditis (HT) was significantly lower, whereas the
      infiltration of FoxP3+ Treg in tissues of PTC with HT tended to be increased.
      CONCLUSIONS: We concluded that the percentage of Treg increased in peripheral
      blood as well as in the tumor tissues of PTC patients compared with that of MNG
      patients. The high percentage of Treg was associated with aggressiveness. There
      may be a compensatory expansion of Treg at the sites of inflammation in tissues
      of PTC with HT contributing to the immune response suppression.

PMID- 25387567
TI  - Differential expression profiling of microRNAs in para-carcinoma, carcinoma and
      relapse human pancreatic cancer.
AB  - PURPOSE: To explore the altered different expression of miRNAs and the mechanisms
      underlying the relapse and metastasis of pancreatic cancer. MATERIALS AND
      METHODS: The most differentially expressed miRNAs were analyzed by gene ontology
      (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway
      analysis and protein interaction analysis. The potentially regulated target genes
      of the most differentially expressed miRNAs were also analyzed further by GO term
      analysis and KEGG pathway analysis, and quantitated by qRT-PCR. RESULTS: In
      total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in
      expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer
      (C/R vs. P). In addition, our study found that pancreatic cancer was related to
      pathways in cancer, including Jak-STAT signaling pathway, MAPK signaling pathway
      and PPAR signaling pathway. CONCLUSIONS: The differential expressed miRNAs and
      their predicted target genes that involved in Jak-STAT signaling pathway, MAPK
      signaling pathway and PPAR signaling pathway indicating their potential roles in
      pancreatic carcinogenesis and progress.

PMID- 25387568
TI  - CMTM5 is reduced in prostate cancer and inhibits cancer cell growth in vitro and
      in vivo.
AB  - PURPOSE: A novel tumor suppressor CKLF-like MARVEL transmembrane domain
      containing member 5 (CMTM5) is reduced or undetectable in many kinds of cancers
      and inhibits tumor cells' malignant features. To explore its role in prostate
      cancer (PCa), we detected its expression patterns in prostate tissues and PCa
      cells, and determined its anti-proliferation functions in PCa cells in vitro and
      in vivo. METHODS: The expression of CMTM5 in prostate tissue microarray,
      specimens and cell lines was evaluated by immunohistochemistry and Western blot,
      respectively. After being transfected with CMTM5 adenovirus or vector, the
      proliferation and migration of DU145 cells were detected by MTT assay and
      transwell assay, respectively. Furthermore, the effects of CMTM5 on tumor growth
      were performed in nude mice xenograft in vivo. RESULTS: We found CMTM5 was
      reduced in PCa tissues and cells compared with BPH tissues, and its expression in
      PCa tissues was related to the Gleason score. Moreover, after being transfected
      with adenovirus, ectopic expression of CMTM5-v1 in DU145 cells led to significant
      inhibition of cell proliferation and migration compared with the control, which
      may be attributed to decreased Akt activity. Finally, restoration of CMTM5
      significantly suppressed tumor growth in vivo. CONCLUSIONS: These results
      indicate that CMTM5 is down-regulated in PCa and exhibit tumor suppressor
      activities in androgen-independent PCa cells. Loss of CMTM5 protein may be
      contributed to the development of PCa and it is a potential therapeutic target
      for castration-resistant prostate cancer.

PMID- 25387569
TI  - The clinical pathological significance of FRAT1 and ROR2 expression in cartilage
      tumors.
AB  - PURPOSE: Chondrosarcoma is a malignant bone tumor with poor prognosis. Surgical
      treatment is the first choice for chondrosarcomas. Chondrosarcoma is not
      sensitive to chemotherapy and radiotherapy. Identification of biological markers
      is important for the early diagnosis and targeted treatment of chondrosarcoma.
      This study investigated the protein expression and clinicopathological
      significance of ROR2 and FRAT1 in 59 chondrosarcomas and 33 osteochondromas.
      METHODS: ROR2 and FRAT1 protein expression in tissues was measured by
      immunohistochemistry. RESULTS: The percentage of positive ROR2 and FRAT1
      expression was significantly higher in patients with chondrosarcoma than in
      patients with osteochondroma (P < 0.01). The percentage of positive ROR2 and
      FRAT1 expression was significantly lower in patients with histological grade I,
      AJCC stage I/II stage, Enneking stage I, non-metastatic and invasive
      chondrosarcoma than patients with histological grade III, AJCC stage III/IV,
      Enneking stage II + III, metastatic and invasive chondrosarcoma (P < 0.05 or P <
      0.01). ROR2 expression was positively correlated with FRAT1 expression in
      chondrosarcoma. Kaplan-Meier survival analysis demonstrated that histological
      grade, AJCC stage, Enneking stage, metastasis, invasion, and ROR2 and FRAT1
      expression significantly correlated with a short mean survival time of patients
      with chondrosarcoma (P < 0.05 or P < 0.01). Cox multivariate analysis showed that
      positive ROR2 and FRAT1 expression was an independent prognostic factor that
      negatively correlated with postoperative survival and positively correlated with
      mortality. CONCLUSION: Positive ROR2 and FRAT1 expression is associated with the
      progression and poor prognosis of chondrosarcoma.

PMID- 25387570
TI  - NETosis is induced by high glucose and associated with type 2 diabetes.
AB  - AIMS: The role of neutrophils in diabetes and its complications is unclear. Upon
      challenge with microbes and inflammatory triggers, neutrophils release enzymes
      and nuclear material, forming neutrophils extracellular traps (NETs) and thereby
      dying by NETosis. We herein tested NET formation and NETosis products in high
      glucose and in the setting of type 2 diabetes (T2D). METHODS: NETosis was
      assessed in vitro in cells exposed to 0, 5, 25 mM glucose and 25 mM mannitol,
      DMSO and PMA using immunofluorescence staining for elastase, DNA and chromatin.
      Single-cell morphometric analysis was used to detect enter of elastase in the
      nucleus and extrusion of nuclear material. Release of NETs was quantified by
      staining with Hoechst 33342. In 38 T2D and 38 age- and sex-matched non-diabetic
      individuals, we determined plasma elastase, mono- and oligonucleosomes and double
      strand (ds) DNA, as circulating NETosis products. RESULTS: NETosis was accurately
      reproduced in vitro: high (25 mM) glucose increased NETosis rate and release of
      NETs compared with 5 mM glucose and 25 mM mannitol. T2D patients showed increased
      plasma elastase, mono- and oligonucleosomes and dsDNA compared with non-diabetic
      control individuals. A positive correlation was found between HbA1c and mono- and
      oligonucleosomes, whereas dsDNA was correlated with the presence of nephropathy
      and cardiovascular disease. Serum IL-6 concentrations were higher in T2D compared
      with CTRL and correlated with serum dsDNA levels. CONCLUSIONS: High glucose and
      hyperglycemia increase release of NETs and circulating markers of NETosis,
      respectively. This finding provides a link among neutrophils, inflammation and
      tissue damage in diabetes.

PMID- 25387573
TI  - Label-free, isothermal and ultrasensitive electrochemical detection of DNA and
      DNA 3'-phosphatase using a cascade enzymatic cleavage strategy.
AB  - Label-free and ultrasensitive electrochemical assays of target DNA and T4
      polynucleotide kinase phosphatase (PNKP) were developed, which took full
      advantage of three enzymes to realize the signal readout and amplification. It
      can ultimately achieve the low detection limits of 10 fM and 1 mU mL(-1) for
      target DNA and PNKP, respectively. 

PMID- 25387576
TI  - Ethical challenges posed by the Ebola virus epidemic in West Africa.
AB  - This paper examines how people in West Africa are reacting to the Ebola virus
      disease, an epidemic presently prevalent in the region. Certain lifestyle changes
      are suggested. Additionally, the heart of the paper focuses on the request by
      governments to be allowed access to experimental drugs, such as Zmapp and TKM
      Ebola, for their infected populations. The author argues that granting such a
      request would circumvent research ethics procedures, which could potentially
      constitute significant risk to users of the drugs. The Pfizer Kano meningitis
      trial of 1996 is cited as an example to buttress how unapproved drugs could prove
      fatal. 

PMID- 25387575
TI  - Comparative metabolomic and ionomic approach for abundant fishes in estuarine
      environments of Japan.
AB  - Environmental metabolomics or ionomics is widely used to characterize the effects
      of environmental stressors on the health of aquatic organisms. However, most
      studies have focused on liver and muscle tissues of fish, and little is known
      about how the other organs are affected by environmental perturbations and
      effects such as metal pollutants or eutrophication. We examined the metabolic and
      mineral profiles of three kinds of abundant fishes in estuarine ecosystem,
      yellowfin goby, urohaze-goby, and juvenile Japanese seabass sampled from Tsurumi
      River estuary, Japan. Multivariate analyses, including nuclear magnetic resonance
      based metabolomics and inductively coupled plasma optical emission spectrometry
      based ionomics approaches, revealed that the profiles were clustered according to
      differences among body tissues rather than differences in body size, sex, and
      species. The metabolic and mineral profiles of the muscle and fin tissues,
      respectively, suggest that these tissues are most appropriate for evaluating
      environmental perturbations. Such analyses will be highly useful in evaluating
      the environmental variation and diversity in aquatic ecosystems. 

PMID- 25387577
TI  - Structure-guided mutational analysis reveals the functional requirements for
      product specificity of DOT1 enzymes.
AB  - DOT1 enzymes are conserved methyltransferases that catalyse the methylation of
      lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas
      African trypanosomes have two homologues, DOT1A and DOT1B, with different
      enzymatic activities. DOT1A mediates mono- and dimethylation of H3K76, the
      homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76
      trimethylation. However, it is unclear how these different enzymatic activities
      are achieved. Here we employ a trypanosomal nucleosome reconstitution system and
      structure-guided homology modelling to identify critical residues within and
      outside the catalytic centre that modulate product specificity. Exchange of these
      residues transfers the product specificity from one enzyme to the other, and
      reveals the existence of distinct regulatory domains adjacent to the catalytic
      centre. Our study provides the first evidence that a few crucial residues in DOT1
      enzymes are sufficient to catalyse methyl-state-specific reactions. These results
      might also have far-reaching consequences for the functional understanding of
      homologous enzymes in higher eukaryotes. 

PMID- 25387578
TI  - IL-17A, IL-17F and IL-23R Gene Polymorphisms in Polish Patients with Rheumatoid
      Arthritis.
AB  - Among the complex network of inflammatory cells involved in the pathogenesis of
      rheumatoid arthritis (RA), Th17 cells have recently been identified as key cells
      in the promotion of autoimmune processes, and joint destruction. The IL-23/Th17
      signalling pathway, consisting of IL-23/IL-23R, IL-17A and IL-17F encoding genes,
      represents a candidate way for RA development with possible involvement in
      disease susceptibility and effect on disease progression. The present study aimed
      to determine the association between the polymorphic variants of the IL-17A
      (rs2275913), IL-17F (rs763780) and IL-23R (rs11209026) genes and RA
      susceptibility, progression and response to therapy with TNF-alpha inhibitors.
      Eighty-nine patients and 125 healthy individuals were investigated. The IL-17A
      polymorphism was found to affect RA progression and response to anti-TNF
      treatment. Female patients carrying the IL-17A wild-type genotype more frequently
      presented with stage 4 (8/24 vs. 6/47; p = 0.058) and were characterized by more
      active disease (the highest DAS28 score >5.1) after 3 months of therapy with the
      TNF inhibitors (12/23 vs. 15/45; p = 0.040). The IL-17F polymorphism appeared to
      be associated with susceptibility to the disease. The presence of the IL-17F
      minor variant (OR 3.97; p < 0.001) and its homozygosity (OR 29.62; p < 0.001) was
      more frequent among patients than healthy individuals. These results suggest that
      the polymorphisms within the IL-17A and IL-17F genes play a significant role in
      RA.

PMID- 25387579
TI  - Mental health status and work environment among workers in small- and medium
      sized enterprises in Guangdong, China-a cross-sectional survey.
AB  - BACKGROUND: Small- and medium-sized enterprises (SMEs) generate nearly 80% of the
      jobs in China, but the dangerous work environment often found in these
      enterprises poses a major concern for public health. Psychosocial pressure and
      mental health problems among the workers are also common in SMEs. However, mental
      health of workers in SMEs is largely neglected in occupational health research
      and practice in China. The purpose of this study is to assess mental health of
      the workers and to explore the associations between physical and psychosocial
      work environment and workers' mental health in SMEs in South China. METHODS: Data
      were collected in 2012 through a cross-sectional survey among 1200 workers
      working in small- and medium-sized enterprises (SMEs) in Guangdong, China. Mental
      health was measured by psychological well-being in the current study. Job Demand
      Control-Support (JDCS) model was used as a theoretical framework to examine the
      psychosocial factors associated with workers' psychological well-being. Data were
      analyzed using SPSS 20.0 and analysis was performed using bivariate analyses and
      multivariate logistic regression. RESULTS: About three in ten workers (35.3%) in
      the sample had poor psychological well-being. Those who were men, younger in age,
      or migrant workers had worse psychological outcome in bivariate analyses. After
      controlling for individual variables (gender, age, marital status, and household
      registration), we found that longer weekly work hours (OR = 1.30, 95% CI: 1.13 ~
      1.50), more exposure to hazardous work environment (OR = 1.26, 95% CI: 1.10 ~
      1.44), higher job demands (OR = 1.29, 95% CI: 1.12 ~ 1.49), and lower job
      autonomy (OR = 0.70, 95% CI: 0.60 ~ 0.81) were significant associated with worse
      psychological well-being. The results were consistent with predictions of the
      JDCS model. CONCLUSIONS: The results indicate that the JDCS model is a useful
      framework in predicting psychological well-being among Chinese workers in SMEs.
      Future mental health promotion should focus on young migrant male workers as they
      appear to be most vulnerable in their psychological well-being. Both physical and
      psychosocial aspects of the work environment should be taken into account in
      policy making to prevent mental disorder and promote psychological well-being
      among workers in SMEs.

PMID- 25387580
TI  - Reply to Yates et al.

PMID- 25387581
TI  - Cough and the transmission of tuberculosis.
AB  - Cough is a predominant feature of respiratory infection and, in tuberculosis, is
      of prime importance for transmitting infection. Tuberculosis is transmitted by
      the air, yet the process by which bacilli are aerosolized has received little
      attention. Features of cough may account for differences in transmission rates
      from source cases of pulmonary disease. We review the literature on the
      mechanisms and characteristics of cough in tuberculosis in the context of the
      dissemination of infection. Coughing is probably more important than other
      respiratory maneuvers, and characteristics of mucus may have an important role
      but data are scarce. Direct mechanisms of cough in tuberculosis are unknown, as
      are temporal and other patterns that correlate with the release of viable
      airborne bacilli. Other than antituberculous chemotherapy and masks, there are
      few methods of modulating cough in tuberculosis. This is an increasingly
      important area for research. 

PMID- 25387582
TI  - Natural history of polyomaviruses in men: the HPV infection in men (HIM) study.
AB  - BACKGROUND: Several new polyomaviruses have been discovered in the last decade,
      including Merkel cell polyomavirus (MCPyV). Little is known about the natural
      history of the more recently discovered polyomaviruses. We estimated the
      incidence, prevalence, and persistence of 9 polyomaviruses (MCPyV, BK
      polyomavirus, KI polyomavirus, JC polyomavirus, WU polyomavirus, Human
      polyomavirus 6 [HPyV6], HPyV7, HPyV9, and Trichodysplasia spinulosa-associated
      polyomavirus) and examined factors associated with MCPyV infection in a
      prospective cohort of 209 men initially enrolled in the HPV Infection in Men
      (HIM) study. METHODS: Participants enrolled at the US site of the HIM study were
      recruited into a substudy of cutaneous viral infections and followed for a median
      of 12.6 months. Eyebrow hair and normal skin swab specimens were obtained at each
      study visit, and the viral DNA load was measured using multiplex polymerase chain
      reaction. RESULTS: MCPyV infection showed the highest prevalence (65.1% of normal
      skin swab specimens and 30.6% of eyebrow hair specimens), incidence (81.7 cases
      per 1000 person-months among normal skin swab specimens, and 24.1 cases per 1000
      person-months among eyebrow hair specimens), and persistence (85.8% of normal
      skin swab specimens and 58.9% of eyebrow hair specimens) among all polyomaviruses
      examined. Age of >44 years (odds ratio [OR], 2.11; 95% confidence interval [CI],
      1.03-4.33) and Hispanic race (OR, 2.64; 95% CI, 1.01-6.88) were associated with
      an increased prevalence of MCPyV infection in eyebrow hair and normal skin swab
      specimens, respectively. CONCLUSION: MCPyV infection is highly prevalent in
      adults, with age and race being predisposing factors.

PMID- 25387583
TI  - High Cytomegalovirus (CMV) DNAemia Predicts CMV Sequelae in Asymptomatic
      Congenitally Infected Newborns Born to Women With Primary Infection During
      Pregnancy.
AB  - OBJECTIVE: We investigated the kinetics of cytomegalovirus (CMV) clearance in
      blood and urine and the relationship between the viral load in blood at birth and
      the development of late-onset sequelae in asymptomatic congenital CMV infection.
      METHODS: Thirty-three newborns with congenital asymptomatic CMV infection born to
      women with primary CMV infection during pregnancy were enrolled. CMV infection
      was monitored by polymerase chain reaction analysis of blood and urine. The
      follow-up examination was concluded at 6 years of age. RESULTS: Ten infants
      developed postnatal sequelae, whereas twenty-three infants remained asymptomatic.
      Fifty percent of babies cleared CMV in blood and urine within 3 and 36 months,
      respectively. Logistic multivariate regression revealed that the risk of neonatal
      clinical disease crossed the level of 50% with a DNAemia at birth of >= 12,000
      copies/mL (P = .0002). The risk of hearing deficit crossed the level of 50% with
      a DNAemia at birth of >= 17,000 copies/mL (P = .0001). No significant difference
      was found between the kinetics of CMV clearance in asymptomatic children as
      compared to babies with late-onset disease. CONCLUSIONS: Asymptomatic newborns
      with a CMV DNAemia at birth of >= 12,000 copies/mL were more likely to experience
      CMV-related sequelae. The risk of hearing deficit increased with a viral load in
      blood of >= 17,000 copies/mL.

PMID- 25387584
TI  - HIV infection and the transmission of tuberculosis.

PMID- 25387585
TI  - Advanced hepatic fibrosis and steatosis are associated with persistent alanine
      aminotransferase elevation in chronic hepatitis C patients negative for hepatitis
      C virus RNA during pegylated interferon plus ribavirin therapy.
AB  - BACKGROUND: Clinical implications of persistent alanine aminotransferase (ALT)
      elevation and associated factors in chronic hepatitis C (CHC) patients who
      achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon
      plus ribavirin (peg-IFN/RBV) therapy remain unknown. METHODS: A total of 1113 CHC
      patients with undetectable HCV RNA during peg-IFN/RBV therapy were enrolled.
      Baseline characteristics associated with persistent on-treatment ALT elevation
      (POAE), and its impact on treatment outcomes, were investigated. RESULTS: Of 1113
      CHC patients, 254 (22.8%) had POAE. Among patients with HCV genotype 1 (HCV-1)
      who had complete early virologic response (EVR) and received 48 weeks of therapy,
      patients with POAE had a lower rate of sustained virologic response (SVR) than
      those without POAE (44.1% vs 74.0%; P = .0002). Multivariate analyses showed that
      body mass index >= 27 kg/m(2), ALT level >=3 times the upper limit of normal,
      aspartate aminotransferase to platelet ratio index score >=1.5, hepatic fibrosis
      >=F3, and hepatic steatosis >=S2 were independent factors associated with POAE
      after viral clearance. CONCLUSIONS: POAE is common in CHC patients during
      therapy. HCV-1 patients with POAE have a lower SVR rate to 48-week therapy if
      they achieve complete EVR. Advanced hepatic fibrosis, obesity, and steatosis are
      factors associated with POAE in these patients.

PMID- 25387586
TI  - Regulation of cerebral CYP2D alters tramadol metabolism in the brain:
      interactions of tramadol with propranolol and nicotine.
AB  - 1. Cytochrome P450 2D (CYP2D) protein is widely expressed across brain regions in
      human and rodents. We investigated the interactions between tramadol, a
      clinically used analgesic, and brain CYP2D regulators, by establishing
      concentration-time curves of tramadol and O-desmethyltramadol (M1) in rat
      cerebrospinal fluid (CSF) and plasma, as well as by analyzing the analgesia-time
      course of tramadol. 2. Propranolol (20 MUg, intracerebroventricular injection),
      CYP2D inhibitor, prolonged the elimination t1/2 of tramadol (40 mg/kg,
      intraperitoneal injection) in the CSF; meanwhile, lower Cmax and AUC0-infinity
      values of M1 were observed. Nicotine (1 mg base/kg, subcutaneous injection, seven
      days), brain CYP2D inducer, induced a shorter Tmax and elevated Cmax of M1 in
      CSF. No differences in the peripheral metabolism of tramadol were observed
      following propranolol and nicotine pretreatment. Nicotine increased areas under
      the analgesia-time curve (AUC) for 0-45 min and 0-90 min of tramadol, which was
      attenuated by propranolol administration. The analgesic actions of tramadol
      positively correlated with cerebral M1 concentration. 3. The results suggest that
      the regulation of brain CYP2D by xenobiotics may cause drug-drug interactions
      (DDIs) of tramadol. Brain CYPs may play an important role in DDIs of centrally
      active substances. 

PMID- 25387587
TI  - Cancer-associated fibroblasts are not formed from cancer cells by epithelial-to
      mesenchymal transition in nu/nu mice.
AB  - Cancer-associated fibroblasts are bioactive elements influencing the biological
      properties of malignant tumors. Their origin from different cell types has been
      established, and the possibility of their formation by epithelial-to-mesenchymal
      transition from cancer cells is under debate. This study shows that human cancer
      cells grafted to nu/nu mice induced formation of tumor stroma with the presence
      of typical smooth muscle actin-containing cancer-associated fibroblasts. These
      cells seem to be of the host origin because they are not recognized by an
      antibody specific for human vimentin, as was also verified in vitro. These
      results suggest that cancer-associated stromal fibroblasts are not formed by
      epithelial-to-mesenchymal transition from cancer cells.

PMID- 25387588
TI  - Volatile emission of decomposing pig carcasses (Sus scrofa domesticus L.) as an
      indicator for the postmortem interval.
AB  - This study aimed at correlating selected carcass borne volatile organic compounds
      (VOCs) with the postmortem interval (PMI). Selected volatiles should 1st be
      reliably emitted during vertebrate decay, 2nd be emitted at high concentrations,
      and 3rd show a reproducible quantitative dynamic during the decaying process.
      Four pigs (Sus scrofa domesticus L.) were placed in a deciduous forest in
      different seasons and volatiles emitted during the decaying process were sampled.
      Seventeen compounds were identified and quantified by GC-MS. Electrophysiological
      experiments on the antenna of female Calliphora vicina and additional data of
      Dermestes maculans were used as an evolutionary tuned information filter to
      evaluate the 1st criterion. The relative quantitative emission of hexanal,
      nonanal, dimethyl disulfide, dimethyl trisulfide, 1-butanol, and phenol were
      correlated with the PMI, and the observed stages of decay and the limitations of
      this model were discussed. 

PMID- 25387589
TI  - Platelet transfusion: a systematic review of the clinical evidence.
AB  - BACKGROUND: Platelet (PLT) transfusion is indicated either prophylactically or
      therapeutically to reduce the risk of bleeding or to control active bleeding.
      Significant uncertainty exists regarding the appropriate use of PLT transfusion
      and the optimal threshold for transfusion in various settings. We formulated 12
      key questions to assess the role of PLT transfusion. STUDY DESIGN AND METHODS: We
      performed a systematic review (SR) of randomized controlled trials (RCTs) and
      observational studies. A comprehensive search of PubMed, Web of Science, and
      Cochrane registry of controlled trials was performed. Methodologic quality of
      included studies was assessed and a meta-analysis was performed if more than two
      studies with similar designs were identified for a specific question. RESULTS:
      Seventeen RCTs and 55 observational studies were included in the final SR.
      Results from RCTs showed a beneficial effect of prophylactic compared with
      therapeutic transfusion for the prevention of significant bleeding in patients
      with hematologic disorders undergoing chemotherapy or stem cell transplantation.
      We found no difference in significant bleeding events related to the PLT count
      threshold for transfusion or the dose of PLTs transfused. Overall methodologic
      quality of RCTs was moderate. Results from observational studies showed no
      evidence that PLT transfusion prevented significant bleeding in patients
      undergoing central venous catheter insertions, lumbar puncture, or other surgical
      procedures. The methodologic quality of observational studies was very low.
      CONCLUSION: We provide a comprehensive assessment of evidence on the use of PLT
      transfusions in a variety of clinical settings. Our report summarizes current
      knowledge and identifies gaps to be addressed in future research.

PMID- 25387590
TI  - Chronic hemolytic anemia and accumulation of pyrimidine nucleotide metabolites.

PMID- 25387591
TI  - Internal hemipelvectomy with reconstruction for primary pelvic neoplasm: a
      systematic review.
AB  - BACKGROUND: Hemipelvectomy is a major operation with significant risks including
      infection, prosthesis failure and fracture. This systematic review was designed
      to review the functional outcomes, oncologic outcomes and complications in
      patients who received internal hemipelvectomy and pelvic reconstruction for
      primary pelvic tumour. METHODS: Searches on MEDLINE, the Cochrane Library, Embase
      and Google Scholar were performed to locate studies involving patients receiving
      internal hemipelvectomy and pelvic reconstruction using a prosthesis, implant or
      bone graft. All studies were either prospective or retrospective observational
      studies published in English. RESULTS: This systematic review included 12 studies
      from 1990 to 2011 involving 217 patients from 5 to 77 years of age who had
      received follow-up for a period from 3 weeks to 15 years. Among the 12 studies,
      the mortality rate, disease-free rate and incidence of local recurrence were 10
      69.2, 23.1-90.0 and 9.1-41.7%, respectively. The post-operative Musculoskeletal
      Tumor Society (MSTS) functional score ranged from 50 to 70 in the more recent
      studies. Compared with prostheses and other implants, patients who received
      allografts had the highest post-operative function, as shown by their MSTS
      scores, but also had a greater incidence of post-operative infection. On the
      other hand, the prosthesis group was associated with the highest percentage of
      fracture and dislocations, as well as other significant complications.
      CONCLUSION: This comprehensive review provided informative details regarding the
      goals, outcomes and complications associated with this procedure and underscored
      the need for further investigation into the various surgical approaches currently
      available.

PMID- 25387593
TI  - The controversy of right ventricular systolic pressure: is it time to abandon the
      pulmonary artery catheter?

PMID- 25387592
TI  - Braking bad: novel mechanisms of CTLA-4 inhibition of T cell responses.
AB  - The coinhibitory receptor cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a master
      regulator of T cell responses and its function is critical in models of
      transplant tolerance. The CD28/CTLA-4 pathway is also an important therapeutic
      target, as the costimulation blocker belatacept was recently approved for use
      following renal transplantation. While the traditional model of CTLA-4
      coinhibition focuses on its ability to directly counteract CD28 costimulation,
      recently this paradigm has significantly broadened. Recent work has uncovered the
      ability of CTLA-4 to act as a cell-extrinsic coinhibitory molecule on CD4(+) T
      cell effectors. While it has been appreciated that CTLA-4 is required for
      FoxP3(+) regulatory T cell (Treg) suppression, current studies have elucidated
      important differences in the function of CTLA-4 on Tregs compared to effectors.
      CTLA-4 expression patterns also differ by T cell subset, with Th17 cells
      expressing significantly higher levels of CTLA-4. Thus, in contrast to the
      traditional model of CTLA-4 as a negative receptor to counter CD28 costimulation,
      recent work has begun to define CTLA-4 as a global regulator of T cell responses
      with subset-specific functions. Future studies must continue to uncover the
      molecular mechanisms that govern CTLA-4 function. These novel findings have
      implications for novel strategies to maximize the regulatory potential of CTLA-4
      during allogeneic T cell responses. 

PMID- 25387594
TI  - A novel type 3 secretion system effector, YspI of Yersinia enterocolitica,
      induces cell paralysis by reducing total focal adhesion kinase.
AB  - Some of the world's most important diseases are caused by bacterial pathogens
      that deliver toxic effector proteins directly into eukaryotic cells using type
      III secretion systems. The myriad of pathological outcomes caused by these
      pathogens is determined, in part, by the manipulation of host cell physiology due
      to the specific activities of individual effectors among the unique suite each
      pathogen employs. YspI was found to be an effector, delivered by Yersinia
      enterocolitica Biovar 1B, that inhibits host cell motility. The action of YspI
      comes about through its specific interaction with focal adhesion kinase, FAK,
      which is a fulcrum of focal adhesion complexes for controlling cellular motility.
      The interaction was defined by a specific domain of YspI that bound to the FAK
      kinase domain. Further examination revealed that YspI-FAK interaction leads to a
      reduction of FAK steady-state levels without altering its phosphorylation state.
      This collection of observations and results showed YspI displays unique
      functionality by targeting the key regulator of focal adhesion complexes to
      inhibit cellular movement.

PMID- 25387595
TI  - Four Japanese cases of dendritic cell neurofibroma with pseudorosettes.
AB  - Dendritic cell neurofibroma with pseudorosettes (DCNWPR) is a rare peripheral
      nerve sheath tumor (PNST). To our knowledge, the only reported case of DCNWPR in
      Japan was documented by our team. We experienced three additional cases of DCNWPR
      in our institute since 2007, and report the clinical and histological features of
      DCNWPR of these Japanese cases. All four patients were adult women, with ages
      ranging 48-77 years (mean, 63.8). All patients presented with small solitary
      lesions that were clinically diagnosed as fibroma, melanocytic nevus or mixed
      tumor of the skin. Three cases were located on the back, and one on the cheek.
      Histopathologically, well-circumscribed nodules were present in the dermis, and
      composed of small lymphocyte-like cells with dark nuclei (type I cells) and
      larger cells with pale vesicular nuclei and abundant eosinophilic cytoplasm (type
      II cells). Small type I cells were grouped concentrically around the larger type
      II cells, thereby forming pseudorosettes. Immunohistochemical studies using
      antibodies against CD57 and S100 protein revealed that type II cells contained a
      copious cytoplasm endowed with a network of slender dendritic extensions. CD57
      should be a useful marker for identifying type II cells because it allows these
      cells to be stained exclusively. We should recognize DCNWPR with its
      characteristic histological features such as pseudorosettes and presence of
      dendritic type II cells as a variant of PNST. 

PMID- 25387596
TI  - Newborn screening for SCID: where are we now?
AB  - Newborn screening (NBS) for severe T-cell lymphopenia/severe combined
      immunodeficiency using the T-cell receptor excision circle assay continues to
      expand in the USA and worldwide. Here, we will review why severe combined
      immunodeficiency is an excellent case for NBS, the outcomes of the first 6 years
      of screening, and dilemmas surrounding screening and management of infants
      detected by NBS. We will also discuss the future of NBS for primary
      immunodeficiencies. 

PMID- 25387597
TI  - Confounding by alcohol use: benzodiazepines and risk of liver cancer.

PMID- 25387598
TI  - Prior authorization in the treatment of patients with pDPN and FM.
AB  - PURPOSE: To determine prior authorization (PA) impact on healthcare utilization,
      costs, and pharmacologic treatment patterns for painful diabetic peripheral
      neuropathy (pDPN) and fibromyalgia (FM). METHODS: This retrospective,
      observational, longitudinal cohort study used medical and pharmacy claims data.
      Newly diagnosed patients treated for FM or pDPN between 7/1/2007 and 12/31/2011
      were included. PA and no PA groups were matched by propensity score 4:1. Medical
      resource utilization, direct medical and pharmacy costs, and treatment pattern
      differences were compared. Pre and postindex differences between PA and no PA
      cohorts were determined by difference in difference analysis. RESULTS: Analysis
      of 2,315 FM patients (1,852 PA; 463 no PA) demonstrated greater increases in
      postindex all-cause costs ($197; P = 0.6673) and disease-related costs ($72; P =
      0.4186) in the PA cohort. Analysis of 1,300 pDPN patients (1,040 PA; 260 no PA)
      demonstrated postindex all-cause cost increases of $1,155 more in the no PA
      cohort (P = 0.6248); disease-related costs decreased $2,809 more in the no PA
      cohort (P = 0.4312). Treatment patterns were similar between cohorts; opioid
      usage was higher in the FM PA cohort (P = 0.0082). CONCLUSIONS: There was no
      evidence of statistically significant differences between PA and no PA cohorts in
      either FM or pDPN populations for total all-cause or disease-related costs.

PMID- 25387599
TI  - Conjugative multiple-antibiotic resistance plasmids in Escherichia coli isolated
      from environmental waters contaminated by human faecal wastes.
AB  - AIMS: To better understand the involvement of faecal contamination in the
      dissemination of antibiotic resistance genes, we investigated the genetic
      supports of resistances in nine multi-resistant Escherichia coli strains
      originating from human faecal contamination, and isolated from three different
      aquatic environments used for producing drinking water. METHODS AND RESULTS:
      Seven strains harboured at least one large plasmid that we have characterized
      (size, antibiotic resistance patterns, incompatibility group, capacity of
      autotransfer, presence of integron). Most of these plasmids were conjugative and
      carried numerous resistances. One of the plasmids studied, belonging to the IncP
      incompatibility group, was able to transfer by conjugation to Pseudomonas
      fluorescens and Aeromonas sp. Only two of the plasmids we studied carried class 1
      and/or 2 integron(s). CONCLUSIONS: Conjugative plasmids isolated from multi
      resistant E. coli strains explained most of the resistances of their host strains
      and probably contribute to the spread of antibiotic resistance genes coming from
      human faecal contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: These results
      highlight the key role played by plasmids in the multi-resistance phenotype of
      faecal bacteria and the diversity of these genetic structures. Contaminated
      water, especially accidentally contaminated drinking water, could be a path back
      to humans for these plasmids.

PMID- 25387600
TI  - The cardiac implantable electronic device power source: evolution and revolution.
AB  - Although the first power source for an implantable pacemaker was a rechargeable
      nickel-cadmium battery, it was rapidly replaced by an unreliable short-life zinc
      mercury cell. This sustained the small pacemaker industry until the early 1970s,
      when the lithium-iodine cell became the dominant power source for low voltage,
      microampere current, single- and dual-chamber pacemakers. By the early 2000s, a
      number of significant advances were occurring with pacemaker technology which
      necessitated that the power source should now provide milliampere current for
      data logging, telemetric communication, and programming, as well as powering more
      complicated pacing devices such as biventricular pacemakers, treatment or
      prevention of atrial tachyarrhythmias, and the integration of innovative
      physiologic sensors. Because the current delivery of the lithium-iodine battery
      was inadequate for these functions, other lithium anode chemistries that can
      provide medium power were introduced. These include lithium-carbon monofluoride,
      lithium-manganese dioxide, and lithium-silver vanadium oxide/carbon mono-fluoride
      hybrids. In the early 1980s, the first implantable defibrillators for high
      voltage therapy used a lithium-vanadium pentoxide battery. With the introduction
      of the implantable cardioverter defibrillator, the reliable lithium-silver
      vanadium oxide became the power source. More recently, because of the demands of
      biventricular pacing, data logging, and telemetry, lithium-manganese dioxide and
      the hybrid lithium-silver vanadium oxide/carbon mono-fluoride laminate have also
      been used. Today all cardiac implantable electronic devices are powered by
      lithium anode batteries. 

PMID- 25387601
TI  - Impact of early tumor shrinkage on clinical outcome in wild-type-KRAS colorectal
      liver metastases treated with cetuximab.
AB  - BACKGROUND AND AIM: To evaluate the impact of early tumor shrinkage (ETS) on long
      term outcome in patients with wild-type Kirsten rat sarcoma viral oncogene
      homolog (KRAS) unresectable colorectal liver metastases (CLM) receiving cetuximab
      plus chemotherapy. METHODS: A total of 138 patients in a randomized controlled
      trial (70 in armA received cetuximab plus chemotherapy, 68 in armB received
      chemotherapy alone), as previously reported (Ye et al., 2013) were included into
      this analysis. The cut-off date updated for overall survival (OS) was June 2014.
      ETS was defined as a >= 20% reduction of the longest diameters of the target
      lesions compared with baseline at the first evaluation (8 weeks). Outcome
      measures were progression-free survival (PFS) and OS. RESULTS: There were 132
      patients available for evaluation, and ETS occurred more frequently in armA than
      that in armB (P = 0.003). ETS was associated with longer OS (armA: 35.7 vs. 19.5
      months, P < 0.001; armB 28.7 vs. 18.7 months, P = 0.01) and PFS (armA: 13.4 vs.
      4.2 months, P < 0.001; armB 7.0 vs. 4.2 months, P = 0.001) compared with patients
      with no-ETS. Among patients with ETS, there was a significant difference between
      armA and armB in PFS (P = 0.03), but not in OS (P = 0.19). All 23 patients who
      underwent liver surgery achieved ETS. In armA, for patients without liver
      surgery, patients observed ETS also gained an increased survival benefit over
      those no-ETS in OS (P = 0.02) and PFS (P < 0.001). ETS was an independent
      predictor of improved OS (hazard ratio 0.56, P = 0.007). CONCLUSION: ETS may
      serve as a predictor of favorable outcome in patients with wild-type KRAS CLM
      receiving cetuximab plus chemotherapy.

PMID- 25387602
TI  - Characterization of excitation-contraction coupling components in human
      extraocular muscles.
AB  - Excitation-contraction coupling (ECC) is the physiological mechanism whereby an
      electrical signal detected by the dihydropyridine receptor, is converted into an
      increase in [Ca2+], via activation of ryanodine receptors (RyRs). Mutations in
      RYR1, the gene encoding RyR1, are the underlying cause of various congenital
      myopathies including central core disease, multiminicore disease (MmD), some
      forms of centronuclear myopathy (CNM) and congenital fibre-type disproportion.
      Interestingly, patients with recessive, but not dominant, RYR1 mutations show a
      significant reduction in RyR protein in muscle biopsies as well as
      ophthalmoplegia. This specific involvement of the extraocular muscles (EOMs)
      indicates that this group of muscles may express different amounts of proteins
      involved in ECC compared with limb muscles. In the present paper, we report that
      this is indeed the case; in particular the transcripts encoding RyR3, cardiac
      calsequestrin (CSQ2) and the alpha1 subunit of the cardiac dihydropyridine
      receptor are up-regulated by at least 100-fold, whereas excitation-coupled Ca2+
      entry is 3-fold higher. These findings support the hypothesis that EOMs have a
      unique mode of calcium handling. 

PMID- 25387603
TI  - Quantum chemical approach to estimating the thermodynamics of metabolic
      reactions.
AB  - Thermodynamics plays an increasingly important role in modeling and engineering
      metabolism. We present the first nonempirical computational method for estimating
      standard Gibbs reaction energies of metabolic reactions based on quantum
      chemistry, which can help fill in the gaps in the existing thermodynamic data.
      When applied to a test set of reactions from core metabolism, the quantum
      chemical approach is comparable in accuracy to group contribution methods for
      isomerization and group transfer reactions and for reactions not including
      multiply charged anions. The errors in standard Gibbs reaction energy estimates
      are correlated with the charges of the participating molecules. The quantum
      chemical approach is amenable to systematic improvements and holds potential for
      providing thermodynamic data for all of metabolism. 

PMID- 25387604
TI  - Transgenic characterization of two testis-specific promoters in the silkworm,
      Bombyx mori.
AB  - Sex-specific regulatory elements are key components for developing insect genetic
      sexing systems. The current insect genetic sexing system mainly uses a female
      specific modification system whereas little success was reported on male-specific
      genetic modification. In the silkworm Bombyx mori, a lepidopteran model insect
      with economic importance, a transgene-based, female-specific lethality system has
      been established based on sex-specific alternative splicing factors and a female
      specific promoter BmVgp (vitellogenin promoter) has been identified. However, no
      male-specific regulatory elements have yet been identified. Here we report the
      transgenic identification of two promoters that drive reporter gene expression in
      a testis-specific manner in B. mori. Putative promoter sequences from the B. mori
      Radial spoke head 1 gene (BmR1) and beta-tubulin 4 gene (Bmbeta4) were introduced
      using piggybac-based germline transformation. In transgenic silkworms, expression
      of the reporter gene enhanced green fluorescent protein (EGFP) directed by either
      BmR1 promoter (BmR1p) or Bmbeta4p showed precisely testis-specific manners from
      the larval to adult stage. Furthermore, EGFP expression of these two transgenic
      lines showed different localization in the testis, indicating that BmR1p or
      Bmbeta4p might be used as distinct regulatory elements in directing testis
      specific gene expression. Identification of these testis-specific promoters not
      only contributes to a better understanding of testis-specific gene function in
      insects, but also has potential applications in sterile insect techniques for
      pest management.

PMID- 25387605
TI  - Space-induced bifurcation in repression-based transcriptional circuits.
AB  - BACKGROUND: Albeit the molecular mechanisms of gene expression are well
      documented, our understanding of their dynamics is much less advanced. Recent
      experimental evidence has revealed that gene expression might be accurately
      organized in space, with several molecular actors localized to specific positions
      in the cell. However, the influence of this spatial localization on the dynamics
      of gene expression is unclear. This issue is also central in synthetic biology,
      where one usually considers the spatial localization in the cell of the genes of
      the inserted synthetic construct as irrelevant for its temporal dynamics.
      RESULTS: Here, we assessed the influence of the spatial distribution of the genes
      on the dynamics of 3-gene transcriptional ring networks regulated by repression,
      i.e. repressilator circuits, using individual-based modelling to simulate their
      dynamics in two and three space dimensions. Our simulations suggest that
      variations of spatial parameters - namely the degree of demixing of the positions
      of the gene or the spatial range of the mRNA and proteins (i.e. the typical
      distance they travel before degradation) - have dramatic effects by switching the
      dynamical regime from spontaneous oscillations to a stationary state where each
      species fluctuates around a constant value. By analogy with the bifurcations
      arising from the variation of kinetic parameters, we referred to those
      transitions as space-induced bifurcations. CONCLUSIONS: Taken together, our
      results strongly support the idea that the spatial organization of the molecular
      actors of transcriptional networks is crucial for the dynamics of gene expression
      and suggest that the spatial localization of the synthetic genes in the cell
      could be used as an additional toggle to control the dynamics of the inserted
      construct in synthetic biology experiments.

PMID- 25387606
TI  - The impact of lubricants on the precision lapping process.
AB  - The impact of lubricants on pole-tip recession and surface morphology of hard
      disk drive heads in the precision lapping process was investigated with atomic
      force microscopy, scanning electron microscopy, and auger electron spectroscopy.
      In particular, the effects of deionized water, hydrocarbon oil, ethanediol,
      isopropanol, and ethanol lubricants were evaluated. The results reveal that
      proper selection of lubricant is critical for achieving optimal performance in
      the lapping process. A mixture of 68% hydrocarbon oil, 30% isopropanol, and 2%
      octadecenoic acid was found to yield the most favorable results, displaying a
      writer shield recession, first shield of reader recession, and surface roughness
      of 0.423, 0.581, and 0.242 nm, respectively. 

PMID- 25387608
TI  - Clinical application of the paraspinal erector approach for spinal canal
      decompression in upper lumber burst fractures.
AB  - OBJECTIVE: Percutaneous pedicle screw fixation is commonly used for upper lumber
      burst fractures. The direct decompression remains challenging with this minimally
      invasive surgery. The objective was to evaluate a novel paraspinal erector
      approach for effective and direct decompression in patients with canal compromise
      and neurologic deficit. METHOD: Patients (n = 21) with neurological deficiency
      and Denis B type upper lumbar burst fracture were enrolled in the study,
      including 14 cases in the L1 and 7 cases in the L2. The patients underwent
      removal of bone fragments from the spinal canal through intervertebral foramen
      followed by short-segment fixation. Evaluations included surgery-related, such as
      duration of surgery and blood loss, and 12-month follow-up, such as the kyphotic
      angle, the height ratio of the anterior edge of the vertebra, the ratio of
      sagittal canal compromise, visual analog scale (VAS), Oswestry Disability Index
      (ODI), and Frankel scores. RESULTS: All patients achieved direct spinal canal
      decompression using the paraspinal erector approach followed by percutaneous
      pedicle screw fixation. The mean operation time (SD) was 173 (23) min, and the
      mean (SD) blood loss was 301 (104) ml. Significant improvement was noted in the
      kyphotic angle, 26.2 +/- 8.7 prior to operation versus 9.1 +/- 4.7 at 12 months
      after operation (p < 0.05); the height ratio of the anterior edge of the injured
      vertebra, 60 +/- 16% versus 84 +/- 9% (p < 0.05); and the ratio of sagittal canal
      compromise, 46.5 +/- 11.4% versus 4.3 +/- 3.6% (p < 0.05). Significant
      improvements in VAS (7.3 +/- 1.2 vs. 1.9 +/- 0.7, p < 0.05), ODI (86.7 +/- 5.8
      vs. 16.7 +/- 5.1, p < 0.05), and Frankel scores were also noted. CONCLUSIONS: The
      paraspinal erector approach was effective for direct spinal canal decompression
      with minimal injury in the paraspinal muscles or spine. Significant improvements
      in spinal function and prognostics were achieved after the percutaneous pedicle
      screw fixation.

PMID- 25387609
TI  - Younger pubertal age is associated with allergy and other atopic conditions in
      girls.
AB  - BACKGROUND: Early menarche is linked to higher incidence of adult asthma,
      suggesting that earlier puberty may influence type 2 immune response
      characteristics of allergic diseases. We examined the hypothesis that timing of
      breast and pubic hair development, which precede menarche, is associated with
      increased childhood atopic conditions. METHODS: Girls were enrolled at 6-8 yr of
      age (2004-2007) in the Breast Cancer and the Environment Research Program Puberty
      Study and were followed through 2011. Pubertal stages were assessed and atopic
      conditions were queried annually. Associations of age at pubertal stage 2 for
      breast or pubic hair development with atopic conditions were assessed using
      prevalence ratios (PR) or odds ratios (OR) and 95% confidence intervals (CI) from
      log-binomial regression and generalized estimating equation models, controlling
      for body mass index and other covariates. A total of 1055 girls with medical and
      pubertal stage data were included. RESULTS: Asthma (ever vs. never) was
      associated with younger pubarche (<=10 vs. >10 yr, PR = 1.15, CI: 1.04-1.28
      adjusted for race/ethnicity and site; PR = 1.13, CI: 1.01-1.25 further adjusted
      for BMI), but not thelarche. In longitudinal models, risk of developing allergies
      increased with younger age at pubarche (adjusted OR = 1.60, CI: 1.10-2.34; <=10
      vs. >10 yr). Risks were highest among black girls with earlier pubarche (n =
      248/326); for allergies, their fully adjusted OR was 2.35, CI: 1.06-5.19 for
      pubarche <=10 vs. >10 yr. CONCLUSIONS: Atopic conditions during childhood are
      associated with younger age at pubarche, independent of obesity, and these
      relationships may vary by racial/ethnic groups.

PMID- 25387610
TI  - Integrating external evidence of intervention effectiveness with both practice
      and the parent perspective: development of 'What Works' for speech, language, and
      communication needs.
AB  - AIM: The aim of the study was to develop an ecologically valid synthesis of the
      evidence underpinning interventions for children with speech, language, and
      communication needs (SLCN), integrating a range of different data sources.
      METHOD: Three sources of information were integrated: the Cochrane Review of
      interventions for children with primary speech and language delays/disorder;
      current practice from an online survey of 534 speech and language therapists and
      other professionals working with children with SLCN; and parent reports of
      preferred outcomes. Evidence was ranked as strong, moderate, or indicative.
      RESULTS: Of the 58 interventions identified, three (5%) were found to have a
      strong level of evidence, 32 (56%) had moderate evidence, and 23 (39%) had
      indicative evidence. Five were universal interventions, the remainder targeted
      and universal. The integrated findings were then turned into an online
      interactive database, which is moderated and updated at regular intervals.
      INTERPRETATION: There are a number of interventions that have a moderate or
      strong level of evidence underpinning them but they tend not to be those used by
      practitioners who often favour well-established familiar programmes even if they
      have only indicative evidence. There is a degree of complementarity between
      professional and parent views about outcomes, albeit with different emphases.

PMID- 25387611
TI  - Novel starters for old processes: use of Saccharomyces cerevisiae strains
      isolated from artisanal sourdough for craft beer production at a brewery scale.
AB  - The deliberate inoculation of yeast strains isolated from food matrices such as
      wine or bread, could allow the transfer of novel properties to beer. In this
      work, the feasibility of the use of baker's yeast strains as starters for craft
      beer production has been evaluated at laboratory and brewery scale. Nine out of
      12 Saccharomyces cerevisiae strains isolated from artisanal sourdoughs
      metabolized 2 % maltose, glucose and trehalose and showed growth rates and cell
      populations higher than those of the brewer's strain Safbrew-S33. Analysis of
      allelic variation at 12 microsatellite loci clustered seven baker's strains and
      Safbrew-S33 in the main group of bread isolates. Chemical analyses of beers
      produced at a brewery scale showed significant differences among the beers
      produced with the baker's strain S38 or Safbrew-S33, while no significant
      differences were observed when S38 or the brewer's strain Safbrew-F2 was used for
      re-fermentation. The sensory profile of beers obtained with S38 or the brewer's
      yeasts did not show significant differences, thus suggesting that baker's strains
      of S. cerevisiae could represent a reservoir of biodiversity for the selection of
      starter strains for craft beer production.

PMID- 25387612
TI  - Heterologous expression of hyperthermophilic cellulases of archaea Pyrococcus sp.
      by fungus Talaromyces cellulolyticus.
AB  - Talaromyces cellulolyticus (formerly known as Acremonium cellulolyticus) is one
      of the high cellulolytic enzyme-producing fungi. T. cellulolyticus exhibits the
      potential ability for high amount production of enzyme proteins. Using the
      homologous expression system under the control of a glucoamylase promoter, some
      kinds of cellulases of T. cellulolyticus can be expressed by T. cellulolyticus.
      On the other hand, hyperthermophilic cellulase has been expected to be useful in
      the industrial applications to biomass. The hyperthermophilic archaea Pyrococcus
      horikoshii and P. furiosus have GH family 5 and 12 hyperthermophilic
      endocellulase, respectively. The two kinds of hyperthermophilic endocellulases
      were successfully produced by T. cellulolyticus using the above expression system
      under the control of a glucoamylase promoter of T. cellulolyticus. These
      recombinant cellulases exhibited the same characteristics as those of the
      recombinant cellulases prepared in E. coli. The productions of the recombinant
      enzymes were estimated to be over 100 mg/L. In this study, we first report the
      overexpression of the hyperthermophilic enzymes of archaea using the fungal
      expression system.

PMID- 25387613
TI  - Ebola virus disease: a review on epidemiology, symptoms, treatment and
      pathogenesis.
AB  - Currently, West Africa is facing the largest outbreak of Ebola virus disease
      (EVD) in history. The virus causing this outbreak, the Zaire Ebolavirus (EBOV),
      belongs to the genus Ebolavirus which together with the genus Marburgvirus forms
      the family of the Filoviridae. EBOV is one of the most virulent pathogens among
      the viral haemorrhagic fevers, and case fatality rates up to 90% have been
      reported. Mortality is the result of multi-organ failure and severe bleeding
      complications. By 18 September 2014, the WHO reported of 5335 cases (confirmed,
      suspected and probable) with 2622 deaths, resulting in a case fatality rate of
      around 50%. This review aims to provide an overview of EVD for clinicians, with
      the emphasis on pathogenesis, clinical manifestations, and treatment options. 

PMID- 25387614
TI  - Modulation of the Abeta peptide aggregation pathway by KP1019 limits Abeta
      associated neurotoxicity.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that is increasing
      worldwide due to increased life expectancy. AD is characterized by two
      pathological hallmarks in the brain: amyloid-beta (Abeta) plaque deposits and
      neurofibrillary tangles. A focus of AD research has concentrated on either
      inhibiting Abeta peptide aggregation that leads to plaque formation or breaking
      down pre-formed Abeta peptide aggregates. An alternative approach is to modulate
      the Abeta aggregation profile by facilitating the formation of Abeta species that
      are off-pathway and non-toxic. Herein, we report the re-purposing of the widely
      studied Ru(iii) anti-cancer complex KP1019, towards regulating the aggregation
      profile of the Abeta peptide. Using electron paramagnetic resonance (EPR)
      spectroscopy, we conclude that KP1019 binds to histidine residues, located at the
      N-terminus of the peptide, in a rapid and robust fashion. Native gels and
      transmission electron microscopy (TEM) analyses have provided insight into the
      species and structures that are generated by KP1019-Abeta interactions. Finally,
      incubation in an in vitro human neuronal cell model has demonstrated that the
      formation of KP1019-Abeta species rescues cell viability from Abeta-associated
      neurotoxicity. Modulation of the Abeta aggregation pathway via covalent
      interactions with small molecules is thus a promising AD therapeutic strategy.

PMID- 25387615
TI  - Cerebral venous thrombosis: Endovascular therapy.

PMID- 25387616
TI  - Emerging MRI and metabolic neuroimaging techniques in mild traumatic brain
      injury.
AB  - Traumatic brain injury (TBI) is one of the leading causes of death worldwide, and
      mild traumatic brain injury (mTBI) is the most common traumatic injury. It is
      difficult to detect mTBI using a routine neuroimaging. Advanced techniques with
      greater sensitivity and specificity for the diagnosis and treatment of mTBI are
      required. The aim of this review is to offer an overview of various emerging
      neuroimaging methodologies that can solve the clinical health problems associated
      with mTBI. Important findings and improvements in neuroimaging that hold value
      for better detection, characterization and monitoring of objective brain injuries
      in patients with mTBI are presented. Conventional computed tomography (CT) and
      magnetic resonance imaging (MRI) are not very efficient for visualizing mTBI.
      Moreover, techniques such as diffusion tensor imaging, magnetization transfer
      imaging, susceptibility-weighted imaging, functional MRI, single photon emission
      computed tomography, positron emission tomography and magnetic resonance
      spectroscopy imaging were found to be useful for mTBI imaging. 

PMID- 25387617
TI  - Once myasthenic, always myasthenic? observations on the behavior and prognosis of
      myasthenia gravis in a cohort of 100 patients.
AB  - BACKGROUND: The natural history of myasthenia gravis [MG] is unpredictable: In
      the first few years the disease course is worst with subsequent gradual disease
      stabilization. However, some patients tend to have continued disease activity or
      resurgence of the disease many years into the illness. The factors correlating
      with disease course need further evaluation. AIMS: To study the patterns of
      remissions, worsening and exacerbations in patients with MG and correlate various
      factors affecting them. SETTINGS AND DESIGN: Retrospective, Institute Review
      Board (IRB) approved study in tertiary referral neurology center. MATERIALS AND
      METHODS: Hundred patients with acquired MG confirming the inclusion criteria were
      studied. Pharmacological remissions, complete stable remissions, exacerbations,
      worsening episodes were analyzed with respect to age of onset, disease extent,
      disease severity at onset and worst of illness, acetyl choline receptor antibody
      positivity, thymectomy status, period of disease, pharmacotherapy and crisis
      episodes. RESULTS AND CONCLUSIONS: In this cohort the percentage of new remission
      rates per year steadily declined after the first year. Ocular myasthenia had
      lesser clinical worsening episodes and high chance of complete stable remission.
      Generalized disease had less chance drug free remission. The risk of episodes of
      worsening persisted at a steady rate over a period of time, being maximum in the
      first year. The risk of exacerbations was unpredictable and could occur after
      prolonged clinical quiescence, often was related to reduction of
      immunosuppression. The disease course did not differ significantly in the
      juvenile and adult age-groups. There was a strong case for permanent
      immunomodulation in MG.

PMID- 25387618
TI  - Diagnostic and prognostic significance of suPAR in traumatic brain injury.
AB  - BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a highly
      sensitive marker that reflects increased inflammation and is positively
      correlated with pro-inflammatory biomarkers. The aim of this prospective
      observational study was to explore the relationship between the plasma
      concentration of suPAR and traumatic brain injury (TBI). MATERIALS AND METHODS:
      In all 112 patients with TBI were included. Patients coming within 12 h whose
      highest abbreviated injury score (AIS) was 3 or less (other than head injury)
      were considered to be isolated TBI. Blood samples were obtained on admission. In
      all ninety healthy volunteers were enrolled as control group. Levels of plasma
      suPAR were determined using an enzyme-linked immunosorbent assay (ELISA) kit
      according to the manufacturer's instructions. Plasma D-dimer was measured and
      Glasgow Coma Scale (GCS) score was assessed at the same time. RESULTS: Plasma
      suPAR values were statistically significantly higher in TBI patients than in
      controls (patients; 14.89 +/- 6.94, controls; 2.79 +/- 0.69, P < 0.01). The suPAR
      levels were strongly associated with the severity of TBI patients. The suPAR
      levels increased in association with the severity of brain injury, significance
      being found among all three groups: severe, moderate and mild TBI. The suPAR
      levels in non-survivals were significantly increased compared to the survivals (P
      < 0.05). Plasma levels of suPAR were strongly correlated to the GCS score (r = 
      0.854) and the levels of D-dimer (r = 0.753, both P < 0.01). Receiver operating
      characteristic curve (ROC) analysis of suPAR levels indicated that suPAR values
      had a high diagnostic specificity and sensitivity to differentiate survivals from
      non-survivals, the area underneath the ROC curve (AUROC) was 0.801 (95% CI: 0.698
      0.903). The optimal suPAR cut-off value in predicting mortality was 15.70 ng/ml
      (sensitivity: 70.4%; specificity: 65.9%). CONCLUSIONS: Plasma levels of suPAR are
      elevated in TBI patients. Prognosis was worse in the patient group with elevated
      suPAR. High suPAR levels indicate a poorer prognosis in TBI patients.

PMID- 25387619
TI  - Accuracy and precision of targeting using frameless stereotactic system in deep
      brain stimulator implantation surgery.
AB  - OBJECTIVES: To assess the accuracy of targeting using NexFrame frameless
      targeting system during deep brain stimulation (DBS) surgery. MATERIALS AND
      METHODS: Fifty DBS leads were implanted in 33 patients using the NexFrame
      (Medtronic, Minneapolis, MN) targeting system. Postoperative thin cut CT scans
      were used for lead localization. X, Y, Z coordinates of the tip of the lead were
      calculated and compared with the intended target coordinates to assess the
      targeting error. Comparative frame-based data set was obtained from randomly
      selected 33 patients during the same period that underwent 65 lead placements
      using Leksell stereotactic frame. Euclidean vector was calculated for directional
      error. Multivariate analysis of variance was used to compare the accuracy between
      two systems. RESULTS: The mean error of targeting using frameless system in medio
      lateral plane was 1.4 mm (SD +/- 1.3), in antero-posterior plane was 0.9 mm (SD
      +/- 1.0) and in supero-inferior plane Z was 1.0 mm (SD +/- 0.9). The mean error
      of targeting using frame-based system in medio-lateral plane was 1.0 mm (SD +/-
      0.7), in antero-posterior plane was 0.9 mm (SD +/- 0.5) and in supero-inferior
      plane Z was 0.7 mm (SD +/- 0.6). The error in targeting was significantly more (P
      = 0.03) in the medio-lateral plane using the frameless system as compared to the
      frame-based system. Mean targeting error in the Euclidean directional vector
      using frameless system was 2.2 (SD +/- 1.6) and using frame-based system was 1.7
      (SD +/- 0.6) (P = 0.07). There was significantly more error in the first 25 leads
      placed using the frameless system than the second 25 leads (P = 0.0015).
      CONCLUSION: The targeting accuracy of the frameless system was lower as compared
      to frame-based system in the medio-lateral direction. Standard deviations (SDs)
      were higher using frameless system as compared to the frame-based system
      indicating lower accuracy of this system. Error in targeting should be considered
      while using frameless stereotactic system for DBS implantation surgery.

PMID- 25387620
TI  - Prevalence of middle cerebral artery stenosis in asymptomatic subjects of more
      than 40 years age group: a transcranial Doppler study.
AB  - INTRODUCTION: Middle cerebral artery (MCA) disease is the most common vascular
      lesion in stroke. Transcranial Doppler (TCD) is a non-invasive bedside screening
      method for assessing cerebral blood flow. AIM: To investigate the prevalence of
      MCA stenosis in asymptomatic but high-risk individuals for stroke. MATERIALS AND
      METHODS: Prospective study between December 2011 and December 2013. Vascular risk
      factors considered included: hypertension (HTN), diabetes mellitus, smoking,
      alcohol consumption, coronary artery disease (CAD), peripheral vascular disease
      (PVD), hypercholesterolemia and obesity. TCD was performed with portable machine
      through the temporal windows by use of a standardized protocol. RESULTS: Of the
      427 subjects, 374 were analyzed; males 264 (70.6%) and females 110 (29.4%). Mean
      age was 54.2 +/- 7.6 years. The frequency of the risk factors was: HTN 287
      (76.7%), diabetes 220 (58.8%), CAD 120 (32.1%), hypercholesterolemia 181 (48.4%),
      smoking 147 (39.3%), alcohol 99 (26.5%), obesity 198 (52.9%) and PVD 8 (2.1%). Of
      the 374 subjects, 27 (7.2%) had intracranial arterial stenosis and the rest had
      normal intracranial arteries. On univariate analysis, subjects with higher age,
      HTN, CAD, smoking and hypercholesterolemia had higher risk of having intracranial
      arterial stenosis (P < 0.05). Multivariate analysis showed HTN and CAD are
      independent risk factors for intracranial arterial stenosis. CONCLUSIONS: Overall
      prevalence of intracranial arterial stenosis is 7.2% in high-risk population
      sample from Hyderabad in South India. HTN and CAD are independent risk factors
      for the development of intracranial arterial stenosis.

PMID- 25387621
TI  - A comparative study of psychiatric comorbidity, quality of life and disability in
      patients with migraine and tension type headache.
AB  - OBJECTIVES: To compare psychiatric co-morbidity, quality of life and disability
      between patients of migraine and tension type headache and healthy controls.
      MATERIALS AND METHODS: Study subjects included 40 consecutive adult patients each
      with migraine and tension type of headache (TTH) of either gender fulfilling
      International Headache Society-II criteria and suffering for 2 years They were
      recruited from a headache clinic in a tertiary care teaching hospital and were
      assessed on Mini International Neuropsychiatric Interview (MINI), World Health
      Organization Quality of Life-BREF (WHOQOL-BREF) Hindi version and the Headache
      Impact Test-6 (HIT-6). Age and sex matched 40 healthy controls were assessed on
      MINI and WHOQOL-BREF. The three groups were compared for statistical significance
      on various scales. RESULTS: Depression emerged as the most prevalent psychiatric
      disorder in both the headache groups. There was significant impairment in quality
      of life on all domains along with functional disability in subjects with both
      types of headache. CONCLUSION: Psychiatric comorbidity, especially depression is
      common in patients with migraines and tension type headache. Quality of life and
      functional ability are significantly impaired in these patients. The clinician
      should remain aware of consequences of prolonged headache, and should provide
      timely intervention.

PMID- 25387622
TI  - Role of local thrombolysis in cerebral hemorrhagic venous infarct.
AB  - BACKGROUND: Chemical thrombolysis in cerebral venous thrombosis (CVT) is one of
      the treatment options and the data is limited. SETTINGS AND DESIGN: Prospective
      observational nonrandomized study. SUBJECTS AND METHODS: This is a prospective
      study of 10 patients (six females and four males) admitted between May 2007 and
      June 2013. Grading system proposed by Department of Interventional Neuroradiology
      (INR), King Edward Memorial Hospital (KEM), Mumbai was used to grade the clinical
      status at admission. There were six patients with clinical Grade 3, two with
      Grade 4, and two with Grade 5. Patients with either Grade less than 3 or more
      than Grade 5 were excluded. Those patients, who were diagnosed with Cerebral
      venoussinous thrombosis (CSVT) but without hemorrhagic venous infarct and treated
      according to INR KEM criteria, were excluded from the study. Average duration of
      thrombolysis was 13 hours (range 10-18 hours). Average dose of urokinase was 12.2
      lakh units (range 9.2-16.8 lakh units). RESULTS: Six patients presented with
      clinical Grade 3 had modified Rankin Scale (mRS) sore of 1 at 30-day follow-up.
      Of the two patients with Grade 4, one had mRS 1 and the other had mRS 2 at 30-day
      follow-up. Of the two patients with Grade 5, one had mRS 2 at 30-day follow-up
      and the other did not respond to local thrombolysis and succumb to intracranial
      hemorrhagic infarct within 48 hours. CONCLUSION: This small prospective single
      center study showed local dural venous thrombolysis significantly improves
      clinical and radiological outcome in patients with CVT. A randomized control
      trial with large sample size is needed to substantiate our findings.

PMID- 25387623
TI  - Anatomic study and clinical significance of extended endonasal anterior skull
      base surgery.
AB  - OBJECTIVE: This study is to investigate the anatomical relationship of endonasal
      approach for anterior skull base surgery, and to determine the boundaries between
      anterior basicranial craniotomy and the security of operative techniques.
      MATERIALS AND METHODS: A total of 10 adult dry skulls and 13 adult cadaveric
      heads processed by formalin were examined under operating microscope. The micro
      anatomic structures of the turbinate, sphenoid sinus, ethmoid sinus, anterior
      ethmoidal artery, posterior ethmoidal artery and anterior skull base were
      observed. Artificial anatomy was performed and the deep-seated regions of the
      surgical approach were observed under operating microscope and endoscope.
      RESULTS: Examined from the intracranial and intranasal aspects, it was found that
      the middle turbinate, uncinate process, ethmoid bulla, lamina papyracea, anterior
      ethmoid canal, posterior ethmoid canal, prominence of the optic canal and
      opticocarotid recess were all important anatomic landmarks for surgery. The
      horizontal distances between medial orbital wall on both sides at the level of
      crista galli, anterior ethmoid canal, and posterior ethmoid canal were (22.31 +/-
      3.08) mm, (23 +/- 2.93) mm, and (26.25 +/- 2.88) mm, respectively. The distance
      between the double optic canal cranial opening was (14.67 +/- 3.82) mm.
      CONCLUSIONS: During the endonasal approach for anterior skull base surgery, full
      advantage of the surgical corridor made by the middle turbinate resection should
      be taken. To control intraoperative bleeding, it is critical to identify anterior
      and posterior ethmoidal artery. Identification and protection of medial orbital
      wall and the optic nerve, and controlling the ranges of anterior basicranial
      craniotomy are of great importance for surgical safety.

PMID- 25387624
TI  - Endoscopic management of CSF rhinorrhea.
AB  - BACKGROUND: Transnasal endoscopic repair has become the treatment of choice for
      most anterior cranial and all sphenoid sinus breaches. The aim of this paper is
      to evaluate the results of endoscopic management of cerebrospinal fluid (CSF)
      rhinorrhea in a tertiary care center in South India. MATERIALS AND METHODS: A
      retrospective analysis of 40 consecutive patients who underwent endoscopic repair
      of CSF rhinorrhea between 2010 and 2013 was performed. Endoscopic procedure
      consisted of defining the defect and removal of mucosa for 3-4 mm surrounding it.
      Repair was done using septal cartilage (for defects involving sphenoid sinus
      where sinus was packed with fat), fascia lata, oxidized cellulose, and fibrin
      sealant. Lumbar drain was placed for 2-4 days in selected cases. A lumbar
      peritoneal shunt was inserted in patients with spontaneous CSF rhinorrhea and
      high opening lumbar CSF pressure. RESULTS: Spontaneous CSF leaks were more common
      in middle-aged females, whereas posttraumatic CSF leaks were common in young
      adult males. The success rates following first surgery for patients with
      posttraumatic, spontaneous, and postprocedural CSF leaks were 85.7, 81.8, and
      75%, respectively, which improved to 95.7, 100, and 100% following second
      procedure, respectively. Technical failures, poor graft uptake because of
      radiation therapy, location of leak in the lateral sphenoid recess, lumbar
      peritoneal shunt malfunction, and poor healing of skull base fractures were
      responsible for recurrence of leak. CONCLUSION: Team work between neurosurgeons
      and otorhinolaryngologists with attention to identification of site of leak,
      preparation of graft bed, securing the graft in place, and postoperative care is
      critical to achieve a high level of success for endoscopic repair of CSF
      rhinorrhea.

PMID- 25387625
TI  - Delayed presentation of post-traumatic bilateral cervical facet dislocation: a
      series of 4 cases.

PMID- 25387626
TI  - Gangliocytic paraganglioma of filum terminale: report of a rare case.

PMID- 25387627
TI  - Primary plasmacytoma of the anterior skull base: a rare case.

PMID- 25387628
TI  - An unusually aggressive clinical behavior in a case of atypical subependymal
      giant cell astrocytoma.

PMID- 25387629
TI  - Giant oculomotor nerve schwannoma presenting as a sellar and suprasellar mass
      with parasellar extension.

PMID- 25387630
TI  - Pilomyxoid astrocytoma in an elderly patient: a case report and review of
      literature.

PMID- 25387631
TI  - A case of cerebral pheohyphomycosis in an immunocompetent patient: emphasis on
      intraoperative findings.

PMID- 25387632
TI  - Co-occurrence of basilar artery and cerebral venous sinus thrombosis in
      antiphospholipid antibody syndrome.

PMID- 25387633
TI  - Silicone neuropatty: an innovative protective tool.

PMID- 25387634
TI  - Cerebral venous thrombosis masquerading as hemicrania continua.

PMID- 25387635
TI  - Charles Bonnet syndrome in a case of cerebral venous thrombosis with fMRI-EEG
      correlation.

PMID- 25387636
TI  - Levetiracetam for tardive dystonia: a case report.

PMID- 25387637
TI  - A rare association of intracranial vertebral artery fenestration with
      nonaneurysmal perimesencephalic subarachnoid hemorrhage.

PMID- 25387638
TI  - Renal small cell carcinoma presenting with solitary lumbar intradural metastasis.

PMID- 25387639
TI  - Corpus callosal hemorrhage due to deep cerebral venous sinus thrombosis.

PMID- 25387640
TI  - Spontaneous thrombosis of a cerebral arteriovenous malformation.

PMID- 25387641
TI  - Hypoglossal nerve palsy: a rare consequence of dengue fever.

PMID- 25387642
TI  - Post-traumatic blepharocele: a rare manifestation of head injury.

PMID- 25387643
TI  - A case of vertebral artery dissection coincides with ipsilateral posterior
      inferior cerebellar artery dissection.

PMID- 25387644
TI  - Radiation-induced cavernous angioma in an adult.

PMID- 25387645
TI  - Acute severe backache: do not forget to look beneath the disc.

PMID- 25387646
TI  - Ocular reverberations of an intracranial blast: a neurosurgical image.

PMID- 25387647
TI  - White epidermoid at the foramen magnum.

PMID- 25387648
TI  - Angiographic "Tau (tau)" sign in persistent trigeminal artery.

PMID- 25387649
TI  - Multiple hemorrhagic infarcts in thrombotic thrombocytopenic purpura.

PMID- 25387650
TI  - Why standard deviation as a measure of dispersion needs a mention in a dataset?

PMID- 25387651
TI  - Erratum to: Correlation between otitis media and dental malocclusion in children.

PMID- 25387652
TI  - Inflammatory Stress Exacerbated Mesangial Foam Cell Formation and Renal Injury
      via Disrupting Cellular Cholesterol Homeostasis.
AB  - Inflammation and lipids play significant roles in the progression of chronic
      kidney disease. This study was designed to investigate whether inflammation
      disrupts cellular cholesterol homeostasis and causes the lipid nephrotoxicity in
      vitro and in vivo, and explored its underlying mechanisms. Inflammatory stress
      was induced by cytokines (interleukin-1beta (IL-1beta); tumor necrosis factor
      alpha (TNF-alpha)) to human mesangial cells (HMCs) in vitro and by subcutaneous
      casein injection in C57BL/6J mice in vivo. The data showed that inflammatory
      stress exacerbated renal cholesterol ester accumulation in vitro and in vivo.
      Inflammation increased cellular cholesterol uptake and synthesis via upregulating
      the expression of low-density lipoprotein receptor (LDLr) and 3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMGCoA-R), while it decreased cholesterol
      efflux via downregulating the expression of liver X receptor alpha and ATP
      binding cassette transporter A1. The increased lipid accumulation by inflammatory
      stress induced reactive oxygen species (ROS) and increased levels of endoplasmic
      reticulum (ER) stress markers (inositol-requiring protein 1 and activating
      transcription factor 6) in HMCs and kidneys of C57BL/6J mice. This study implied
      that inflammation promoted renal lipid accumulation and foam cell formation by
      disrupting cellular cholesterol homeostasis. Increased intracellular lipids under
      inflammatory stress caused oxidative stress and ER stress in vitro and in vivo
      which may contribute to renal injury and progression of chronic kidney disease. 

PMID- 25387653
TI  - Challenges in Measuring Benefit of Clinical Research Training Programs--the ASH
      Clinical Research Training Institute Example.
AB  - The American Society of Hematology developed the Clinical Research Training
      Institute (CRTI) to address the lack of training in patient-oriented research
      among hematologists. As the program continues, we need to consider metrics for
      measuring the benefits of such a training program. This article addresses the
      benefits of clinical research training programs. The fundamental and key
      components are education and mentorship. However, there are several other
      benefits including promotion of collaboration, job and advancement opportunities,
      and promotion of work-life balance. The benefits of clinical research training
      programs need to be measured so that funders and society can judge if they are
      worth the investment in time and resources. Identification of elements that are
      important to program benefit is essential to measuring the benefit of the program
      as well as program planning. Future work should focus on the constructs which
      contribute to benefits of clinical research training programs such as CRTI. 

PMID- 25387654
TI  - [Pre- and postoperative fast-track treatment concepts in spinal surgery : patient
      information and patient cooperation].
AB  - BACKGROUND: Evidence-based procedures and pathways to reduce peri- and
      postoperative complications, while simultaneously achieving a high satisfaction
      rate of patients and lower costs are important goals in the treatment of
      orthopedic patients. PURPOSE: This article describes the key factors to improve
      treatment of patients with indications for stabilization of one or two segments
      in the field of degenerative lumbar spine pathologies. A fast-track concept was
      developed to optimize the pathway of treatment, while increasing patient
      satisfaction and shortening the hospital stay. In the present patient cohort,
      significantly greater patient satisfaction and significantly shorter hospital
      stays were achieved. RESULTS: The hospital stay was reduced from 10.9 to 6.2 days
      after introduction of a multimodal patient school that was held 10 days prior to
      admission, with mobilization on the day of surgery with a strictly followed
      treatment plan supervised by therapists and taking into account the patient's own
      assessment, as well an early plan for discharge based on fixed established
      criteria. This concept is a very successful tool to achieve high quality standard
      of treatment paired with a reduction of hospital stay.

PMID- 25387655
TI  - Efficacy and safety of strong acid electrolyzed water for peritoneal lavage to
      prevent surgical site infection in patients with perforated appendicitis.
AB  - PURPOSE: Our previous experimental study of perforated peritonitis in rats proved
      that peritoneal lavage with strong acid electrolyzed water (SAEW) has no adverse
      effects, reduces the bacteria count in the ascitic fluid more effectively than
      saline, and increases the survival rate significantly. Thus, we conducted a
      randomized controlled study, applying SAEW in the treatment of perforated
      appendicitis in children. METHODS: Forty-four patients, aged 3-14 years, were
      randomly divided into two groups: Group S (n = 20), in which the peritoneal
      cavity was lavaged with 100 ml/kg saline and the wound was washed out with 200 ml
      saline; and Group E (n = 24), in which the peritoneal cavity was lavaged with 100
      ml/kg SAEW and the wound was washed out with 200 ml SAEW. RESULTS: No adverse
      effect of SAEW was observed in Group E. There was no difference in the bacterial
      evanescence ratio of ascitic fluid after lavage between Groups S and E (11.1 and
      15.8%, respectively). A residual abscess developed in one patient from each group
      (5.0 and 4.2%, respectively). The incidence of surgical site infection (SSI) was
      significantly lower in Group E than in Group S (0 and 20%, respectively; P <
      0.05). There was no difference in the duration of pyrexia, positive C-reactive
      protein, leukocytosis, or hospital stay between the groups. CONCLUSION:
      Peritoneal lavage and wound washing with SAEW have no adverse effects and are
      effective for preventing SSI.

PMID- 25387656
TI  - Advantages of the prone position for minimally invasive esophagectomy in
      comparison to the left decubitus position: better oxygenation after minimally
      invasive esophagectomy.
AB  - PURPOSE: The aim of this retrospective study was to evaluate whether minimally
      invasive esophagectomy (MIE) in the prone position has advantages over the left
      decubitus position. METHOD: A total of 110 consecutive patients with esophageal
      cancer who had undergone MIE were included in the analysis. The clinical outcomes
      were compared between 51 patients treated in the prone position (prone group) and
      59 patients treated in the left decubitus position (LD group). The main outcome
      was postoperative respiratory complications and postoperative oxygenation
      [arterial oxygen pressure/fraction of inspired oxygen (P/F ratio)]. The secondary
      outcomes included the length of the operation, blood loss, number of dissected
      lymph nodes, postoperative morbidities and mortality. RESULTS: The P/F ratio
      after the operation was significantly higher in the prone group (0 h: P = 0.01,
      12 h: P < 0.001). No significant differences were observed in the frequency of
      respiratory complications (P = 0.89). The blood loss in the prone group was
      significantly lower (P < 0.001), and the number of dissected intrathoracic lymph
      nodes was significantly higher (P = 0.03) than in the LD group. No significant
      differences were observed in the frequencies of overall postoperative
      complications. CONCLUSION: MIE in the prone position preserves better oxygenation
      of patients during the early recovery period, and is associated with less blood
      loss and a larger number of dissected lymph nodes.

PMID- 25387657
TI  - Risk factors for a persistent type 2 endoleak after endovascular aneurysm repair.
AB  - PURPOSE: To investigate the natural course of type 2 endoleaks (T2Es) and to
      identify the risk factors associated with a persistent T2E after endovascular
      aneurysm repair (EVAR). METHODS: The medical records of patients who underwent
      EVAR for the treatment of an atherosclerotic abdominal aortic aneurysm between
      October 2006 and December 2011 at our institute were reviewed. T2Es were
      diagnosed by contrast-enhanced computed tomography within 4 weeks of EVAR, and
      patients were followed up at 6 and 12 months. In cases where a T2E was detected,
      the blood vessels responsible for the T2E were identified and statistically
      analyzed for their association with a persistent T2E. RESULTS: We identified T2Es
      in 111 of 469 patients within 4 weeks of undergoing EVAR. During the follow-up,
      41 patients (36.9 %) showed spontaneous resolution of their T2E. The percentage
      of patients with a T2E was 75.4, 69.2 and 58.0 % at 6, 12 and 24 months,
      respectively. T2E caused by defects in multiple vessels and T2E associated with
      the fourth lumbar artery were identified as risk factors associated with a
      persistent T2E in the univariate analysis. In the multivariate analysis, T2E
      caused by multiple vessels was identified as the only independent risk factor for
      a persistent T2E. CONCLUSIONS: We identified T2E caused by multiple vessel
      failure as an independent risk factor for persistent T2E.

PMID- 25387659
TI  - Spina bifida occulta and aperta: a review of current treatment paradigms.
AB  - Spina bifida remains a challenging neurosurgical entity to manage despite both an
      increased awareness of the disease as well as a decreased incidence due to folic
      acid supplementation. We review the spectrum of neural tube defects, which are
      the second most common serious congenital defect and the most common of the
      central nervous system, and discuss the latest management paradigms. The
      challenges of timely diagnosis and treatment of spina bifida occulta and the
      latest advances in fetal repair of spina bifida aperta (myelomeningocele) will be
      discussed. The authors review the literature and share their experience with
      managing neural tube defects. 

PMID- 25387658
TI  - Clinical outcomes of laparoscopic versus open surgery for primary tumor resection
      in patients with stage IV colorectal cancer with unresectable metastasis.
AB  - PURPOSE: The aim of this study was to compare the clinical outcomes of
      laparoscopic surgery with those of open surgery in patients with colorectal
      cancer and unresectable metastasis. METHODS: We retrospectively reviewed the
      medical records of patients who underwent primary tumor resection of colorectal
      cancer with unresectable metastasis between January 2001 and December 2010.
      RESULTS: Of 280 patients, 61 underwent laparoscopic surgery and 219 underwent
      open surgery. Regarding the short-term outcomes, the amount of blood loss was
      lower in the laparoscopic group (P = 0.014), although the operation was longer in
      the laparoscopic group (P = 0.003). The times to flatus (P < 0.001), liquid food
      intake (P < 0.001), and the duration of hospital stay (P < 0.001) were shorter in
      the laparoscopic group. The complication rate was lower in the laparoscopic group
      than in the open group (P = 0.043). Although the overall survival was
      significantly better in the laparoscopic group in a univariate analysis, there
      was no significant difference in the overall survival between the two groups in a
      multivariate analysis (P = 0.482). CONCLUSIONS: Laparoscopic surgery seems to be
      a safe and feasible option, with short-term benefit for primary tumor resection
      in patients with stage IV colorectal cancer with unresectable metastasis.

PMID- 25387660
TI  - Synthesis of unsymmetrical N-carboranyl NHCs: directing effect of the carborane
      anion.
AB  - The syntheses of unsymmetrical N-heterocyclic carbenes (NHCs) that contain a
      single N-bound icosahedral carborane anion substituent are reported. Both anionic
      C-2 and doubly deprotonated dianionic C-2/C-5 NHC lithium complexes are isolated.
      The latter species is formed selectively, which reveals a surprising directing
      effect conveyed by icosahedral carborane anion substituents. 

PMID- 25387661
TI  - Comparison of burden among primary care-givers of children with autism and
      intellectual disability against children with intellectual disability only in a
      hospital population in India.
AB  - OBJECTIVE: To compare the burden among the primary caregivers (PCG) of children
      with autism and intellectual disability (ASD + ID) against intellectual
      disability (ID) only, and identify the factors that predict high caregiver
      burden. METHODS: Children with either ASD + ID (N = 41) or ID (N = 56) and their
      PCG were recruited and assessed using the Family Burden Interview Schedule, Binet
      Kamat Scale of Intelligence or Gesell's Developmental Schedule and Vineland
      Social Maturity Scale, Childhood Autism Rating Scale, Sensory Profile and Brief
      Autism Mealtime Behavior Inventory after collecting the socio-demographic
      details. Appropriate bivariate and multivariate statistical test were used.
      RESULTS: The total burden and level of burden was similar among PCG of children
      with ASD + ID and ID (P = 0.8). However, financial burden (P = 0.03) and burden
      due to the effects on the physical health of other family members (P = 0.03) was
      more among the ID group. The burden due to the effects on family interaction was
      more (P = 0.009) in the ASD + ID group. The socio-economic status (OR = 3.60; P =
      0.03) and the kinship of the primary care-giver (OR = 0.37; P = 0.008) were
      significantly associated with high level of burden. In addition, the diagnosis,
      and gender of the child contributed to the prediction model for high level of
      burden. CONCLUSIONS: The interventions for children with ASD + ID and ID should
      have modules to address burden among PCG. Disability specific burden alleviating
      strategies should be used among PCG who are at risk of having high burden.

PMID- 25387662
TI  - Masking and demasking strategies for the BF2-BODIPYs as a tool for BODIPY
      fluorophores.
AB  - An efficient and chemoselective route for transforming BF2-BODIPYs to Et2B
      BODIPYs (masking) was developed using Et2AlCl. The Et groups can be easily
      replaced with F atoms using BF3.Et2O in moist CH2Cl2 to regenerate the BF2
      BODIPYs (demasking). The masking-demasking strategy is very useful for
      synthesizing functionalized BODIPYs via nucleophilic and reductive reactions. The
      masking strategy was used to synthesize a BODIPY dimer by McMurry coupling of a
      formyl Et2B-BODIPY, while a new BODIPY with an asymmetrically substituted B
      center was synthesized using the demasking strategy. 

PMID- 25387663
TI  - Non-pegylated liposomal doxorubicin in lymphoma: patterns of toxicity and outcome
      in a large observational trial.
AB  - The anthracycline doxorubicin plays a major role in the treatment of
      lymphoproliferative disorders. However, its use is often limited due to cardiac
      toxicity, which seems to be much less in the liposomal non-pegylated formulation
      (Myocet(r)). The aim of this study was the evaluation of efficacy and toxicity of
      Myocet(r)-containing treatment regimens, with a focus on cardiotoxicity during
      treatment in lymphoma patients. A total of 326 consecutive patients, treated
      between March 2008 and December 2013 in 11 Austrian and 1 Italian cancer centers,
      were retrospectively assessed. Patients' baseline and treatment-related
      parameters were obtained by reviewing hospital records. Median age was 74 years
      (range 26-93). The most common histology was DLBCL (60 %), followed by FL (13 %)
      and MCL (8 %). At least one cardiovascular comorbidity was present in 72 % of
      patients. Most common grade 3/4 toxicities were hematologic, namely, leukopenia,
      neutropenia, thrombocytopenia, and febrile neutropenia in 44, 40, 17, and 16 %.
      Overall, 43 patients suffered a cardiac event (any grade) with most patients
      developing congestive heart failure. Parameters significantly associated with
      severe cardiac events (grades 3-5) were the presence of cardiovascular
      comorbidities, chronic obstructive pulmonary disease, and elevated baseline NT
      proBNP. Treatment response after first line Myocet(r)-containing therapy was >=58
      % among all entities (range 58-86 %) and therefore comparable to those of
      conventional therapeutic regimens. Herein, we provide a detailed toxicity profile
      of Myocet(r)-containing chemotherapy regimens. Despite the high rate of patients
      with preexisting comorbidities, the number of adverse events was encouraging.
      However, these results need to be confirmed in a prospective randomized trial.

PMID- 25387664
TI  - Interobserver variance in myelodysplastic syndromes with less than 5 % bone
      marrow blasts: unilineage vs. multilineage dysplasia and reproducibility of the
      threshold of 2 % blasts.
AB  - Previous studies have shown the reproducibility of the 2008 World Health
      Organization (WHO) classification in myelodysplastic syndromes (MDS), especially
      when multilineage dysplasia or excess of blasts are present. However, there are
      few data regarding the reproducibility of MDS with unilineage dysplasia. The
      revised International Prognostic Scoring System R-IPSS described two new
      morphological categories, distinguishing bone marrow (BM) blast cell count
      between 0-2 % and >2- < 5 %. This distinction is critical for establishing
      prognosis, but the reproducibility of this threshold is still not demonstrated.
      The objectives of our study were to explore the reliability of the 2008 WHO
      classification, regarding unilineage vs. multilineage dysplasia, by reviewing 110
      cases previously diagnosed with MDS, and to study whether the threshold of <=2 %
      BM blasts is reproducible among different observers. We used the same methodology
      as in our previous paper [Font et al. (2013) Ann Hematol 92:19-24], by
      encouraging investigators to include patients with <5 % BM blasts. Samples were
      collected from 11 hospitals and were evaluated by 11 morphologists. Each observer
      evaluated 20 samples, and each sample was analyzed independently by two
      morphologists. Discordance was observed in 36/108 suitable cases (33 %, kappa
      test 0.503). Diagnosis of MDS with unilineage dysplasia (refractory cytopenia
      with unilineage dysplasia (RCUD), refractory anemia with ring sideroblasts (RARS)
      or unclassifiable MDS) was assessed in 33 patients, by either of the two
      observers. We combined this series with the cases with RCUD or RARS included in
      our 2013 paper, thus obtaining 50 cases with unilineage dysplasia by at least one
      of the observers. The whole series showed very low agreement regarding RCUD
      (5/23, 21 %) and RARS (5/28, 18 %). Regarding BM blast count, the threshold of
      <=2 % was not reproducible (discordance rate 32/108 cases, kappa test 0.277). Our
      study shows that among MDS WHO 2008 categories, interobserver discordance seems
      to be high in cases with unilineage dysplasia. We also illustrate that the
      threshold of <=2 % BM blasts as settled by the R-IPSS may be not easy to
      reproduce by morphologists in real practice.

PMID- 25387665
TI  - Pharmacological properties of JTE-052: a novel potent JAK inhibitor that
      suppresses various inflammatory responses in vitro and in vivo.
AB  - OBJECTIVE: To evaluate the pharmacological properties of JTE-052, a novel Janus
      kinase (JAK) inhibitor. METHODS: The JAK inhibitory activity of JTE-052 was
      evaluated using recombinant human enzymes. The inhibitory effects on cytokine
      signaling pathways were evaluated using primary human inflammatory cells. The in
      vivo efficacy and potency of JTE-052 were examined in a mouse interleukin (IL)-2
      induced interferon (IFN)-gamma production model and a rat collagen-induced
      arthritis model. RESULTS: JTE-052 inhibited the JAK1, JAK2, JAK3, and tyrosine
      kinase (Tyk)2 enzymes in an adenosine triphosphate (ATP)-competitive manner and
      inhibited cytokine signaling evoked by IL-2, IL-6, IL-23, granulocyte/macrophage
      colony-stimulating factor, and IFN-alpha. JTE-052 inhibited the activation of
      inflammatory cells, such as T cells, B cells, monocytes, and mast cells, in
      vitro. Oral dosing of JTE-052 resulted in potent suppression of the IL-2-induced
      IFN-gamma production in mice with an ED50 value of 0.24 mg/kg, which was more
      potent than that of tofacitinib (ED50 = 1.1 mg/kg). In the collagen-induced
      arthritis model, JTE-052 ameliorated articular inflammation and joint destruction
      even in therapeutic treatments where methotrexate was ineffective. CONCLUSIONS:
      The present results indicate that JTE-052 is a highly potent JAK inhibitor, and
      represents a candidate anti-inflammatory agent for suppressing various types of
      inflammation.

PMID- 25387666
TI  - Use of conventional PCR and smear microscopy to diagnose pulmonary tuberculosis
      in the Amazonian rainforest area.
AB  - The diagnostic usefulness of Ziehl-Neelsen (ZN)-stained sputum smears combined
      with conventional polymerase chain reaction (ZN/PCR) to amplify IS6110 region DNA
      extracted from ZN slides was evaluated. The objective was to verify if this
      association could improve tuberculosis (TB) diagnosis in patients at remote
      sites. The study was carried out in 89 patients with culture-confirmed pulmonary
      TB as defined by the Brazilian Manual for TB Treatment. The participants were
      recruited in a reference unit for TB treatment in Rondonia, a state in the
      Amazonian area in northern Brazil. ZN, PCR, and culture performed in the sputum
      samples from these patients were analyzed in different combinations (i.e., ZN
      plus PCR and ZN plus culture). The prevalence rates of pulmonary TB in these
      patients were 32.6 and 28.1% considering culture and ZN/PCR, respectively. The
      sensitivity and specificity of ZN/PCR were 86 and 93%, respectively. ZN/PCR was
      able to detect more TB cases than ZN alone. This method could offer a new
      approach for accurate tuberculosis diagnosis, especially in remote regions of the
      world where culture is not available.

PMID- 25387667
TI  - DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is
      effective for VEGF-C methylation and for inhibiting cancer growth.
AB  - DNA hypomethylation may activate oncogene transcription, thus promoting
      carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl
      donor in numerous methylation reactions and acts as an inhibitor of intracellular
      demethylase activity, which results in hypermethylation of DNA. The main
      objectives of this study were to determine whether DNA hypomethylation correlated
      with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of
      SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression
      was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by
      immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by
      bisulfite DNA sequencing. The effect of SAM on cell apoptosis was assayed by flow
      cytometry analyses and its effect on cancer growth was assessed in nude mice. The
      VEGF-C promoters of MGC-803, BGC-823, and SGC-7901 gastric cancer cells, which
      normally express VEGF-C, were nearly unmethylated. After SAM treatment, the VEGF
      C promoters in these cells were highly methylated and VEGF-C expression was
      downregulated. SAM also significantly inhibited tumor growth in vitro and in
      vivo. DNA methylation regulates expression of VEGF-C. SAM can effectively induce
      VEGF-C methylation, reduce the expression of VEGF-C, and inhibit tumor growth.
      SAM has potential as a drug therapy to silence oncogenes and block the
      progression of gastric cancer.

PMID- 25387668
TI  - Stability of XIST repression in relation to genomic imprinting following global
      genome demethylation in a human cell line.
AB  - DNA methylation is essential in X chromosome inactivation and genomic imprinting,
      maintaining repression of XIST in the active X chromosome and monoallelic
      repression of imprinted genes. Disruption of the DNA methyltransferase genes
      DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA
      hypomethylation and biallelic expression of the imprinted gene IGF2 but does not
      lead to reactivation of XIST expression, suggesting that XIST repression is due
      to a more stable epigenetic mark than imprinting. To test this hypothesis, we
      induced acute hypomethylation in HCT116 cells by 5-aza-2'-deoxycytidine (5-aza
      CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA
      methylation by microarray and monitoring the expression of XIST and imprinted
      genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression
      in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly
      expressed only under acute hypomethylation conditions, indicating the importance
      of XIST repression in the active X to cell survival. Given that DNMT3A is the
      only active DNMT in DKO cells, it may be responsible for ensuring the repression
      of XIST in those cells. Taken together, our data suggest that XIST repression is
      more tightly controlled than genomic imprinting and, at least in part, is due to
      DNMT3A.

PMID- 25387669
TI  - Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis
      of periodontal ligament fibroblasts.
AB  - Diabetics have an increased prevalence of periodontitis, and diabetes is one of
      the causative factors of severe periodontitis. Apoptosis is thought to be
      involved in this pathogenic relationship. The aim of this study was to
      investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by
      advanced glycation end products (AGEs) and their receptor (RAGE). We examined the
      roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus
      using cultured PDL fibroblasts that were treated by AGE-modified bovine serum
      albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment
      (control). Microscopy and real-time quantitative PCR indicated that PDL
      fibroblasts treated with AGE-BSA were deformed and expressed higher levels of
      RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE
      BSA reduced cell viability (69.80 +/- 5.50%, P<0.01) and increased apoptosis
      (11.31 +/- 1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl
      transferase-mediated nick-end labeling revealed that AGE-BSA significantly
      increased apoptosis of PDL fibroblasts. The results showed that the changes in
      PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and
      exacerbates periodontium destruction.

PMID- 25387670
TI  - Targeting PPM1D by lentivirus-mediated RNA interference inhibits the
      tumorigenicity of bladder cancer cells.
AB  - Protein phosphatase magnesium/manganese-dependent 1D (PPM1D) is a p53-induced
      phosphatase that functions as a negative regulator of stress response pathways
      and has oncogenic properties. However, the functional role of PPM1D in bladder
      cancer (BC) remains largely unknown. In the present study, lentivirus vectors
      carrying small hairpin RNA (shRNA) targeting PPM1D were used to explore the
      effects of PPM1D knockdown on BC cell proliferation and tumorigenesis. shRNA
      mediated knockdown of PPM1D significantly inhibited cell growth and colony
      forming ability in the BC cell lines 5637 and T24. Flow cytometric analysis
      showed that PPM1D silencing increased the proportion of cells in the G0/G1 phase.
      Downregulation of PPM1D also inhibited 5637 cell tumorigenicity in nude mice. The
      results of the present study suggest that PPM1D plays a potentially important
      role in BC tumorigenicity, and lentivirus-mediated delivery of shRNA against
      PPM1D might be a promising therapeutic strategy for the treatment of BC.

PMID- 25387671
TI  - Possible roles of COX-1 in learning and memory impairment induced by traumatic
      brain injury in mice.
AB  - People who suffer from traumatic brain injury (TBI) often experience cognitive
      deficits in spatial reference and working memory. The possible roles of
      cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are
      far from well known. Adult mice subjected to TBI were treated with the COX-1
      selective inhibitor SC560. Performance in the open field and on the beam walk was
      then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days
      following injury. Acquisition of spatial learning and memory retention was
      assessed using the Morris water maze on day 15 post-TBI. The expressions of COX
      1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor
      (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and
      synaptophysin were detected in TBI mice. Administration of SC560 improved
      performance of beam walk tasks as well as spatial learning and memory after TBI.
      SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and
      reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin
      in TBI mice. The present findings demonstrated that COX-1 might play an important
      role in cognitive deficits after TBI and that selective COX-1 inhibition should
      be further investigated as a potential therapeutic approach for TBI.

PMID- 25387672
TI  - Acute stress-induced antinociception is cGMP-dependent but heme oxygenase
      independent.
AB  - Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase
      (HO), participates as a neuromodulator in physiological processes such as
      thermoregulation and nociception by stimulating the formation of 3',5'-cyclic
      guanosine monophosphate (cGMP). In particular, the acute physical restraint
      induced fever of rats can be blocked by inhibiting the enzyme HO. A previous
      study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive
      role in modulating noninflammatory acute pain. Thus, this study evaluated the
      involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress
      in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the
      tail flick test. The results showed that antinociception induced by acute stress
      was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO
      inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was
      dependent on cGMP activity because pretreatment with the guanylate cyclase
      inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the
      increase in the AI induced by acute stress.

PMID- 25387673
TI  - Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in
      rats by activating the phosphoinositide-3-kinase/Akt pathway.
AB  - The aim of this study was to investigate the effect of propofol pretreatment on
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the
      phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure.
      Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the
      lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor
      necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in bronchoalveolar
      lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA.
      Lung injury was assayed via lung histological examination. PI3K and p-Akt
      expression levels in the lung tissue were determined by Western blotting.
      Propofol pretreatment prolonged survival, decreased the concentrations of
      protein, TNF-alpha, and IL-6 in BALF, attenuated ALI, and increased PI3K and p
      Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with
      wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study
      indicates that propofol pretreatment attenuated LPS-induced ALI, partly by
      activation of the PI3K/Akt pathway.

PMID- 25387674
TI  - Modulatory effects of taurine on jejunal contractility.
AB  - Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and
      has diverse pharmacological effects. However, the role of taurine in modulating
      smooth muscle contractility is still controversial. We propose that taurine (5-80
      mM) can exert bidirectional modulation on the contractility of isolated rat
      jejunal segments. Different low and high contractile states were induced in
      isolated jejunal segments of rats to observe the effects of taurine and the
      associated mechanisms. Taurine induced stimulatory effects on the contractility
      of isolated rat jejunal segments at 3 different low contractile states, and
      inhibitory effects at 3 different high contractile states. Bidirectional
      modulation was not observed in the presence of verapamil or tetrodotoxin,
      suggesting that taurine-induced bidirectional modulation is Ca(2+) dependent and
      requires the presence of the enteric nervous system. The stimulatory effects of
      taurine on the contractility of isolated jejunal segments was blocked by atropine
      but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked
      activation was involved in the stimulatory effects when isolated jejunal segments
      were in a low contractile state. The inhibitory effects of taurine on the
      contractility of isolated jejunal segments were blocked by propranolol and L-NG
      nitroarginine but not by phentolamine, suggesting that adrenergic beta receptors
      and a nitric oxide relaxing mechanism were involved when isolated jejunal
      segments were in high contractile states. No bidirectional effects of taurine on
      myosin phosphorylation were observed. The contractile states of jejunal segments
      determine taurine-induced stimulatory or inhibitory effects, which are associated
      with muscarinic receptors and adrenergic beta receptors, and a nitric oxide
      associated relaxing mechanism.

PMID- 25387675
TI  - Role of high mobility group box-1 and protection of growth hormone and
      somatostatin in severe acute pancreatitis.
AB  - In this study, we investigated the potential role of high-mobility group box 1
      (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G)
      and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of
      20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and
      pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA
      expression was measured by reverse transcription-PCR. Levels of circulating TNF
      alpha, IL-1, IL-6, and endotoxin were also measured. In the SAP group,
      interstitial congestion and edema, inflammatory cell infiltration, and
      interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of
      HMGB1, TNF-alpha, IL-1, IL-6 and endotoxin were significantly up-regulated in the
      SAP group compared with those in the sham-operated group, and the 7-day survival
      rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the
      morphological structures was alleviated, the levels of HMGB1, TNF-alpha, IL-1, IL
      6, and endotoxin were significantly decreased compared with those in the SAP
      group, and the survival rate was increased. Moreover, in the SAP+G+S group, all
      histological scores were significantly improved and the survival rate was
      significantly higher compared with the SAP group. In conclusion, HMGB1 might
      participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin
      might play a therapeutic role in the inflammatory response of SAP.

PMID- 25387676
TI  - Factors associated with Clostridium difficile diarrhea in a hospital in Beijing,
      China.
AB  - Clostridium difficile is the most common cause of hospital-acquired diarrhea in
      patients treated with antibiotics, chemotherapeutic agents, and other drugs that
      alter the normal equilibrium of the intestinal flora. A better understanding of
      the risk factors for C. difficile-associated disease (CDAD) could be used to
      reduce the incidence of CDAD and the costs associated with its treatment. The aim
      of this study was to identify the risk factors for CDAD in a cohort of Chinese
      patients in a Beijing hospital. Medical charts of a total of 130 inpatients (62
      males and 68 females) with hospital-acquired diarrhea (45 with CDAD; 85 without
      CDAD) were retrospectively reviewed. C. difficile toxins A and B were detected in
      fecal samples using enzyme-linked fluorescence assays. The drugs used by patients
      with and without CDAD before the onset of diarrhea were compared. Factors that
      differed significantly between the two groups by univariate analysis were
      analyzed by multivariate analysis using a logistic regression model. Multivariate
      analysis showed that cephalosporin treatment was associated with a significantly
      higher risk of CDAD in hospitalized patients, while treatment with glycopeptides
      was significantly associated with a reduction in CDAD (P<0.001 for cephalosporin;
      P=0.013 for glycopeptides). Our data confirmed previous findings that empirical
      treatment with cephalosporins is positively associated with CDAD compared to
      individuals using other CDAD-related drugs. Additionally, we showed that
      treatment with glycopeptides was negatively associated with CDAD, compared to
      individuals using other CDAD-related drugs.

PMID- 25387677
TI  - Changes in epidemiology of rotavirus in the Triangulo Mineiro region of Brazil:
      lack of two consecutive rotavirus seasons.
AB  - Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent
      (G1P[8]) vaccine against the virus was introduced into the Brazilian National
      Immunization Program for all infants in March 2006. The objectives of this study
      were to determine the rate and genotype distribution of rotavirus causing
      infantile diarrhea in the Triangulo Mineiro region of Brazil during 2011-2012 and
      to assess the impact of local vaccination. Fecal specimens were analyzed for
      detection and characterization of rotavirus using polyacrylamide gel
      electrophoresis, reverse transcription followed by polymerase chain reaction
      (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7%
      (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence
      intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007)
      in 2012 when compared with available data for baseline years (2005/2006) in
      Uberaba. In Uberlandia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011,
      and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with
      data for 2008. The circulation of rotavirus G2P[4] strains decreased during the
      period under study, and strains related to the P[8] genotype reemerged in the
      region. This study showed a marked and sustained reduction of rotavirus-related
      cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a
      positive impact of the vaccination program.

PMID- 25387678
TI  - A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced
      enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia.
AB  - p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor
      suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid
      leukemia (CML) cells enhances myeloid progenitor formation from common myeloid
      progenitors. Therefore, we examined the effects of overexpressed p15INK4B on
      proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited
      the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4)
      and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of
      K562 cells by upregulating Bax expression and downregulating Bcl-2 expression.
      Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small
      interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction
      of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1
      and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide
      new insights into the role of p15INK4B in CML and a potential therapeutic target
      for overcoming tyrosine kinase inhibitor resistance in CML.

PMID- 25387679
TI  - Psoriasis severity and hypothalamic-pituitary-adrenal axis function: results from
      the CALIPSO study.
AB  - Psoriasis is a chronic inflammatory disease that significantly impacts life
      quality, being associated with stress and mental disorders. We investigated
      whether the activity of the hypothalamic-pituitary-adrenal (HPA) axis was
      associated with psoriasis severity, daily life stress and anxiety, and depressive
      symptoms. In this ancillary study, which was part of the CALIPSO (coronary artery
      calcium in psoriasis) study, saliva was collected from 102 patients with
      psoriasis immediately upon awakening, 30, and 60 min after awakening, at 2:00 pm
      and at bedtime (five time points) to determine salivary cortisol levels. We used
      Pearson's correlation coefficient to evaluate the association of clinical and
      psychopathological variables with HPA activity. We found a direct correlation
      between bedtime cortisol and psoriasis severity evaluated by the psoriasis area
      severity index (PASI; r=0.39, P<0.001). No correlations between other clinical
      and psychopathological variables or with other cortisol assessments were
      observed. The findings indicated that HPA dysfunction may be present in
      psoriasis, as bedtime cortisol was correlated with psoriasis severity. Our study
      is limited by the lack of a control group; therefore, we were not able to explore
      whether these cortisol values were different compared with a concurrent, healthy
      sample. 

PMID- 25387680
TI  - Bromoalkaloids protect primary cortical neurons from induced oxidative stress.
AB  - Bromoalkaloids are secondary metabolites with a demonstrated high activity in
      several therapeutic areas. In this research, we probe the neuroprotective and
      antioxidant activities of hymenialdisine and hymenin. Both structures were tested
      in an oxidative stress cellular model, consisting of cortical neurons that are
      incubated with the oxidative stress inducer hydrogen peroxide and the tested
      compound. Several oxidation biomarkers were analyzed, and the results of the
      oxidative stress induced neurons in the presence and absence of bromoalkaloids
      were compared. Both compounds demonstrated significant neuroprotective ability
      under stress conditions at low nanomolar concentrations, with hymenialdisine
      highlighted for demonstrating a more complete protection. Also, the activity of
      hymenialdisine and hymenin was studied in the nuclear factor erythroid 2-related
      factor 2 (Nrf2)-antioxidant response element (ARE) pathway, and, for the first
      time, these halogenated metabolites are described as Nrf2 inducers, reinforcing
      the antioxidant capacity observed and therefore opening a new path of
      investigation. These results, added to the previously described effect of this
      compound family in negatively modulating several kinases and proinflammatory
      cytokines, position hymenialdisine and hymenin as good candidates for the
      development of new drugs for neurodegenerative diseases. 

PMID- 25387681
TI  - CTLA-4 antibodies: new directions, new combinations.
AB  - Checkpoint blockade is a transformative therapeutic approach to a broad spectrum
      of malignancies because it increases the power of antitumor immunity to obtain
      durable responses. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is the
      prototypical inhibitory checkpoint receptor. Since US Food and Drug
      Administration approval of the anti-CTLA-4 antibody ipilimumab for use in
      patients with melanoma, there has been ever-increasing excitement among
      oncologists about new ways to use this method of releasing the "brakes" on
      patients' endogenous immune systems. This review will summarize the preclinical
      and clinical development of CTLA-4-blocking antibodies, discuss recent insights
      into the biology of CTLA-4 blockade, review the use of these antibodies in
      combination with established and novel therapeutic modalities, and comment on
      ongoing questions regarding their administration. 

PMID- 25387682
TI  - Prospects for targeting PD-1 and PD-L1 in various tumor types.
AB  - Immune checkpoints, such as programmed death ligand 1 (PD-L1) or its receptor,
      programmed death 1 (PD-1), appear to be Achilles' heels for multiple tumor types.
      PD-L1 not only provides immune escape for tumor cells but also turns on the
      apoptosis switch on activated T cells. Therapies that block this interaction have
      demonstrated promising clinical activity in several tumor types. In this review,
      we will discuss the current status of several anti-PD-1 and anti-PD-L1 antibodies
      in clinical development and their direction for the future. 

PMID- 25387683
TI  - Type 2 Diabetes Remission After Gastric Bypass: What Is the Best Prediction Tool
      for Clinicians?
AB  - BACKGROUND: Statistical models and scores have been recently suggested to predict
      remission of type 2 diabetes after bypass surgery, but their relevance in routine
      clinical practice still needs evaluation. Our objective was to assess these
      methods on a French cohort and to compare them with other easy-to-use models.
      METHODS: We investigated a cohort of 84 diabetic obese subjects who underwent
      Roux-en-Y gastric bypass surgery. Diabetes remission 1 year after surgery was
      defined based on the American Diabetes Association criteria. We tested six
      methods from the literature and four other models to predict remission of
      diabetes after bypass surgery using pre-operative bioclinical parameters.
      Predictive methods for diabetes remission were assessed using cross-validation
      error rates when appropriate. RESULTS: Sixty percent of the subjects had diabetes
      remission. Models from the literature had high error rates in our cohort (from
      22.6 to 40.5 %), while published simple scoring systems behaved much better (15.9
      and 16.7 %). Using other apprehensible models learned on our cohort did not
      improve the prediction error (from 17.2 to 19.9 %). CONCLUSIONS: We showed that
      the scoring system DiaRem is easy to use and provides the best prediction error
      (15.9 %) compared to other methods. We additionally propose a DiaRem score
      threshold of <=6 for likely remission of a subject 1 year after surgery, which
      may be considered in clinical decision-making.

PMID- 25387684
TI  - Microwave purification of large-area horizontally aligned arrays of single-walled
      carbon nanotubes.
AB  - Recent progress in the field of single-walled carbon nanotubes (SWNTs)
      significantly enhances the potential for practical use of this remarkable class
      of material in advanced electronic and sensor devices. One of the most daunting
      challenges is in creating large-area, perfectly aligned arrays of purely
      semiconducting SWNTs (s-SWNTs). Here we introduce a simple, scalable, large-area
      scheme that achieves this goal through microwave irradiation of aligned SWNTs
      grown on quartz substrates. Microstrip dipole antennas of low work-function
      metals concentrate the microwaves and selectively couple them into only the
      metallic SWNTs (m-SWNTs). The result allows for complete removal of all m-SWNTs,
      as revealed through systematic experimental and computational studies of the
      process. As one demonstration of the effectiveness, implementing this method on
      large arrays consisting of ~20,000 SWNTs completely removes all of the m-SWNTs
      (~7,000) to yield a purity of s-SWNTs that corresponds, quantitatively, to at
      least to 99.9925% and likely significantly higher. 

PMID- 25387686
TI  - Breastfeeding experience differentially impacts recognition of happiness and
      anger in mothers.
AB  - Breastfeeding is a dynamic biological and social process based on hormonal
      regulation involving oxytocin. While there is much work on the role of
      breastfeeding in infant development and on the role of oxytocin in socio
      emotional functioning in adults, little is known about how breastfeeding impacts
      emotion perception during motherhood. We therefore examined whether breastfeeding
      influences emotion recognition in mothers. Using a dynamic emotion recognition
      task, we found that longer durations of exclusive breastfeeding were associated
      with faster recognition of happiness, providing evidence for a facilitation of
      processing positive facial expressions. In addition, we found that greater
      amounts of breastfed meals per day were associated with slower recognition of
      anger. Our findings are in line with current views of oxytocin function and
      support accounts that view maternal behaviour as tuned to prosocial
      responsiveness, by showing that vital elements of maternal care can facilitate
      the rapid responding to affiliative stimuli by reducing importance of threatening
      stimuli. 

PMID- 25387687
TI  - Dietary squalene supplementation improves DSS-induced acute colitis by
      downregulating p38 MAPK and NFkB signaling pathways.
AB  - SCOPE: Squalene is a polyunsaturated triterpene, which has exhibited anticancer
      and antioxidant activities among others. We investigated dietary squalene
      supplementation effect on an acute colitis model induced by dextran sulfate
      sodium (DSS) in C57BL/6 mice. METHODS AND RESULTS: Mice were fed from weaning
      with squalene at 0.02% and 0.1%. After 4 weeks, mice were exposed to 3% DSS for 5
      days developing acute colitis. After DSS removal (5 days), colons were
      histological and biochemically processed. Our results showed that dietary
      squalene treatment exerts anti-inflammatory action in DSS-induced acute colitis.
      Western blot revealed that squalene downregulated COX-2 (where COX is
      cyclooxygenase) and inducible nitric oxide synthase system by inhibition of
      mitogen-activated protein kinase p38 and the nuclear factor-kappa B signaling
      pathways, preventing an increase in the cytokines levels. Under our experimental
      conditions, STAT3 and FOXP3 (where FOXP3 is forkhead box P3) were not modified
      and the transcriptional regulation of antioxidant and/or detoxifying enzymes,
      Nrf2 (where Nrf2 is nuclear factor (erythroid-derived 2)-like 2), was reduced in
      DSS-induced colitis. However, any change could be observed after squalene
      supplementation. CONCLUSION: Squalene was able to improve the oxidative events
      and returned proinflammatory proteins expression to basal levels probably through
      p38 mitogen-activated protein kinase and nuclear factor-kappa B signaling
      pathways. However, supplementary studies are needed in order to provide a basis
      for developing a new dietary supplementation strategy.

PMID- 25387688
TI  - Dissolved trace metal speciation in estuarine and coastal waters: comparison of
      WHAM/Model VII predictions with analytical results.
AB  - The authors apply the chemical speciation model WHAM/Model VII to investigate the
      distribution of metal species of Fe(III) and the divalent cations of Ni, Cu, Zn,
      Cd, Hg, and Pb, in the water column of estuaries and coastal areas. The authors
      compare, for the same locations, measured and modeled free ion and organically
      bound metal concentrations. The modeled free ion calculations show varying levels
      of agreement with experimental measurements. Where only natural organic matter is
      considered as the organic ligand, for Ni, Cd, and Pb, agreement within 1 order of
      magnitude is found in 122 of 128 comparisons. For Fe and Zn comparisons 12 of 34
      (Fe) and 10 of 18 (Zn) agree to within 1 order of magnitude, the remaining
      modeled values being over 1 order of magnitude higher than measurements. Copper
      measurements agree within 1 order of magnitude of modeled values in 314 of 533
      (59%) cases and are more than 1 order of magnitude lower than modeled values in
      202 cases. There is a general tendency for agreement between modeled and measured
      values to improve with increasing total metal concentrations. There are
      substantial variations among different analysis techniques but no systematic bias
      from the model is observed across techniques. It would be beneficial to cross
      validate the different analytical methods, in combination with further modeling.
      The authors also assessed the effect of including an anthropogenic organic ligand
      (ethylenediamine tetraacetic acid (EDTA)) in the modeling, given its known
      presence in some coastal environments. Except for Cd, all metals were sensitive
      to the presence of EDTA, even at a low concentration of 50 nM.

PMID- 25387689
TI  - Earthworm (Pheretima aspergillum) extract stimulates osteoblast activity and
      inhibits osteoclast differentiation.
AB  - BACKGROUND: The potential benefits of earthworm (Pheretima aspergillum) for
      healing have received considerable attention recently. Osteoblast and osteoclast
      activities are very important in bone remodeling, which is crucial to repair bone
      injuries. This study investigated the effects of earthworm extract on bone cell
      activities. METHODS: Osteoblast-like MG-63 cells and RAW 264.7 macrophage cells
      were used for identifying the cellular effects of different concentrations of
      earthworm extract on osteoblasts and osteoclasts, respectively. The optimal
      concentration of earthworm extract was determined by mitochondrial colorimetric
      assay, alkaline phosphatase activity, matrix calcium deposition, Western blotting
      and tartrate-resistant acid phosphatase activity. RESULTS: Earthworm extract had
      a dose-dependent effect on bone cell activities. The most effective concentration
      of earthworm extract was 3 mg/ml, significantly increasing osteoblast
      proliferation and differentiation, matrix calcium deposition and the expression
      levels of alkaline phosphatase, osteopontin and osteocalcin. Conversely, 3 mg/ml
      earthworm extract significantly reduced the tartrate-resistant acid phosphatase
      activity of osteoclasts without altering cell viability. CONCLUSIONS: Earthworm
      extract has beneficial effects on bone cell cultures, indicating that earthworm
      extract is a potential agent for use in bone regeneration.

PMID- 25387691
TI  - Modeling and simulation analysis of the relationship between lesion recurrence on
      brain images and clinical recurrence in patients with ischemic stroke.
AB  - The objective of current study is to assess the relationship between
      characteristics of patients with acute ischemic stroke and clinical recurrences
      to identify predictors for the prognosis by modeling and simulation. Primary
      endpoint was clinical recurrence of ischemic stroke, and secondary endpoint was
      occurrence of any of the following clinical recurrence of ischemic stroke,
      transient ischemic attack, acute coronary syndrome, or vascular deaths. Time to
      event models were developed by NONMEM((r)) using prospectively collected clinical
      data from 270 patients over 5 years, where 7.0% and 9.3% of them experienced
      lesion recurrence on MRI at 1 month (LR1M) and clinical recurrence, respectively.
      Exponential models best described the data. LR1M and diabetes mellitus history
      were significant predictors for primary endpoint. Times to recurrence for
      patients with LRIM (+) and diabetes mellitus (+) were predicted to be 0.095 and
      0.317 of those for patients with LRIM (-) and diabetes mellitus (-),
      respectively. LR1M was only predictor for secondary endpoint with predicted time
      to recurrence in patients with LR1M (+) compared to 0.141 of LR1M (-).
      Quantitative prediction of clinical recurrence using MRI could improve
      personalized therapy by identifying patients at risk of recurrence, and could
      enable efficient clinical trials by stratifying the patients. 

PMID- 25387690
TI  - The role of Galectin-3 in alpha-synuclein-induced microglial activation.
AB  - BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative
      motor disorder. The neuropathology is characterized by intraneuronal protein
      aggregates of alpha-synuclein and progressive degeneration of dopaminergic
      neurons within the substantia nigra. Previous studies have shown that
      extracellular alpha-synuclein aggregates can activate microglial cells, induce
      inflammation and contribute to the neurodegenerative process in PD. However, the
      signaling pathways involved in alpha-synuclein-mediated microglia activation are
      poorly understood. Galectin-3 is a member of a carbohydrate-binding protein
      family involved in cell activation and inflammation. Therefore, we investigated
      whether galectin-3 is involved in the microglia activation triggered by alpha
      synuclein. RESULTS: We cultured microglial (BV2) cells and induced cell
      activation by addition of exogenous alpha-synuclein monomers or aggregates to the
      cell culture medium. This treatment induced a significant increase in the levels
      of proinflammatory mediators including the inducible Nitric Oxide Synthase
      (iNOS), interleukin 1 Beta (IL-1beta) and Interleukin-12 (IL-12). We then reduced
      the levels of galectin-3 expression using siRNA or pharmacologically targeting
      galectin-3 activity using bis-(3-deoxy-3-(3-fluorophenyl-1H-1,2,3-triazol-1-yl)
      beta-D-galactopyranosyl)-sulfane. Both approaches led to a significant reduction
      in the observed inflammatory response induced by alpha-synuclein. We confirmed
      these findings using primary microglial cells obtained from wild-type and
      galectin-3 null mutant mice. Finally, we performed injections of alpha-synuclein
      in the olfactory bulb of wild type mice and observed that some of the alpha
      synuclein was taken up by activated microglia that were immunopositive for
      galectin-3. CONCLUSIONS: We show that alpha-synuclein aggregates induce
      microglial activation and demonstrate for the first time that galectin-3 plays a
      significant role in microglia activation induced by alpha-synuclein. These
      results suggest that genetic down-regulation or pharmacological inhibition of
      galectin-3 might constitute a novel therapeutic target in PD and other
      synucleinopathies.

PMID- 25387692
TI  - Identification of NY-BR-1-specific CD4(+) T cell epitopes using HLA-transgenic
      mice.
AB  - Breast cancer represents the second most common cancer type worldwide and has
      remained the leading cause of cancer-related deaths among women. The
      differentiation antigen NY-BR-1 appears overexpressed in invasive mammary
      carcinomas compared to healthy breast tissue, thus representing a promising
      target antigen for T cell based tumor immunotherapy approaches. Since efficient
      immune attack of tumors depends on the activity of tumor antigen-specific CD4(+)
      effector T cells, NY-BR-1 was screened for the presence of HLA-restricted CD4(+)
      T cell epitopes that could be included in immunological treatment approaches.
      Upon NY-BR-1-specific DNA immunization of HLA-transgenic mice and functional ex
      vivo analysis, a panel of NY-BR-1-derived library peptides was determined that
      specifically stimulated IFNgamma secretion among splenocytes of immunized mice.
      Following in silico analyses, four candidate epitopes were determined which were
      successfully used for peptide immunization to establish NY-BR-1-specific, HLA
      DRB1*0301- or HLA-DRB1*0401-restricted CD4(+) T cell lines from splenocytes of
      peptide immunized HLA-transgenic mice. Notably, all four CD4(+) T cell lines
      recognized human HLA-DR-matched dendritic cells (DC) pulsed with lysates of NY-BR
      1 expressing human tumor cells, demonstrating natural processing of these
      epitopes also within the human system. Finally, CD4(+) T cells specific for all
      four CD4(+) T cell epitopes were detectable among PBMC of breast cancer patients,
      showing that CD4(+) T cell responses against the new epitopes are not deleted nor
      inactivated by self-tolerance mechanisms. Our results present the first NY-BR-1
      specific HLA-DRB1*0301- and HLA-DRB1*0401-restricted T cell epitopes that could
      be exploited for therapeutic intervention against breast cancer. 

PMID- 25387693
TI  - House finch responses to Mycoplasma gallisepticum infection do not vary with
      experimentally increased aggression.
AB  - Aggression can alter infectious disease dynamics through two, non-exclusive
      mechanisms: 1) increasing direct contact among hosts and 2) altering hosts'
      physiological response to pathogens. Here we examined the latter mechanism in a
      social songbird by manipulating intraspecific aggression in the absence of direct
      physical contact. We asked whether the extent of aggression an individual
      experiences alters glucocorticoid levels, androgen levels, and individual
      responses to infection in an ecologically relevant disease model: house finches
      (Haemorhous mexicanus) infected with Mycoplasma gallisepticum (MG). Wild-caught
      male finches were housed in one of three settings, designed to produce increasing
      levels of aggression: 1) alone, with no neighbor ("no neighbor"), 2) next to a
      sham-implanted stimulus male ("sham neighbor"), or 3) next to a testosterone
      implanted stimulus male ("testosterone neighbor"). Following one week of social
      treatment, focal males were experimentally infected with MG, which causes severe
      conjunctivitis and induces sickness behaviors such as lethargy and anorexia.
      While social treatment increased aggression as predicted, there were no
      differences among groups in baseline corticosterone levels, total circulating
      androgens, or responses to infection. Across all focal individuals regardless of
      social treatment, pre-infection baseline corticosterone levels were negatively
      associated with the severity of conjunctivitis and sickness behaviors, suggesting
      that corticosterone may dampen inflammatory responses in this host-pathogen
      system. However, because corticosterone levels differed based upon population of
      origin, caution must be taken in interpreting this result. Taken together, these
      results suggest that in captivity, although aggression does not alter individual
      responses to MG, corticosterone may play a role in this disease.

PMID- 25387696
TI  - CdS nanoflake arrays for highly efficient light trapping.
AB  - CdS nanoflake arrays (NFAs) exhibit unprecedented light absorption capability,
      and they can serve as a scaffold to load thin organic absorbers for
      extraordinarily high light absorption. As a result, the hybrid solar cell
      consisting of NFAs and organic absorber yields a ten-times high short-circuit
      photocurrent compared to the counterpart device with a common planar structure. 

PMID- 25387694
TI  - A new monoclonal antibody DAG-6F4 against human alpha-dystroglycan reveals
      reduced core protein in some, but not all, dystroglycanopathy patients.
AB  - We generated a novel monoclonal antibody, DAG-6F4, against alpha-dystroglycan
      which immunolabels the sarcolemma in human muscle biopsies. Its seven amino-acid
      epitope, PNQRPEL, was identified using phage-displayed peptides and is located
      immediately after the highly-glycosylated mucin domain of alpha-dystroglycan. On
      Western blots of recombinant alpha-dystroglycan, epitope accessibility was
      reduced, but not entirely prevented, by glycosylation. DAG-6F4 immunolabelling
      was markedly reduced in muscle biopsies from Duchenne muscular dystrophy patients
      consistent with disruption of the dystroglycan complex. In a range of
      dystroglycanopathy patients with reduced/altered glycosylation, staining by DAG
      6F4 was often less reduced than staining by IIH6 (antibody against the glycan
      epitope added by LARGE and commonly used to identify glycosylated alpha
      dystroglycan). Whereas IIH6 was reduced in all patients, DAG-6F4 was hardly
      changed in a LARGE patient, less reduced than IIH6 in limb-girdle muscular
      dystrophy type 2I, but as reduced as IIH6 in some congenital muscular dystrophy
      patients. Although absence of the LARGE-dependent laminin-binding site appears
      not to affect alpha-dystroglycan stability at the sarcolemma, the results suggest
      that further reduction in aDG glycosylation may reduce its stability. These
      studies suggest that DAG-6F4 may be a useful addition to the antibody repertoire
      for evaluating the dystroglycan complex in neuromuscular disorders. 

PMID- 25387697
TI  - Implant bone integration importance in forensic identification.
AB  - Odontological identification consists of the comparison of antemortem dental
      information regarding a missing person with postmortem data from an unidentified
      corpse or human remains. Usually, the comparison concerns morphologic features
      that the operator chooses among all the visible characteristics because of inter
      individual uniqueness; for this reason, implants can be of enormous assistance. A
      case concerning the recovery of a burnt oral implant, connected to a bone
      fragment, among 2780 charred bone fragments, suspected to have belonged to a
      victim of homicide, is presented to demonstrate that dental implants and their
      site of bone integration represent a very precious element for personal forensic
      identification. Because of their morphological invariability in time and because
      of their morphologic uniqueness, they were used as evidence to associate
      unidentified human charred remains to a missing person where DNA analysis failed
      to do so. The case illustrates the fundamental contribution, not yet described in
      literature, given by the clinical aspects of tooth replacement with dental
      implants to a forensic discipline. Clinical practitioners should therefore be
      aware of the great importance of their work and of dental records in a forensic
      identification scenario. 

PMID- 25387698
TI  - Septic thrombosis of the internal jugular vein: Lemierre's syndrome revisited.
AB  - OBJECTIVES/HYPOTHESIS: Study of the clinical evolution of a primary ear, nose,
      and throat infection complicated by septic thrombophlebitis of the internal
      jugular vein. STUDY DESIGN: Retrospective case-control study. PATIENTS AND
      METHODS: From 1998 to 2010, 23 patients at our institution were diagnosed with a
      septic thrombosis of the internal jugular vein. Diagnostics included
      microbiologic analysis and imaging such as computed tomography, magnetic
      resonance imaging, and ultrasound. Therapy included broad-spectrum antibiotics,
      surgery of the primary infectious lesion, and postoperative anticoagulation. The
      patients were retrospectively analyzed. RESULTS: The primary infection sites were
      found in the middle ear (11), oropharynx (8), sinus (3), and oral cavity (1).
      Fourteen patients needed intensive care unit treatment for a mean duration of 6
      days. Seven patients were intubated, and two developed severe acute respiratory
      distress syndrome. An oropharynx primary infection site was most prone to a
      prolonged clinical evolution. Anticoagulation therapy was given in 90% of
      patients. All 23 patients survived the disseminated infection without consecutive
      systemic morbidity. CONCLUSION: In the pre-antibiotic time, septic internal
      jugular vein thrombophlebitis was a highly fatal condition with a mortality rate
      of 90%. Modern imaging techniques allow early and often incidental diagnosis of
      this clinically hidden complication. Anticoagulation, intensive antibiotic
      therapy assisted by surgery of the primary infection site, and intensive
      supportive care can reach remission rates of 100%.

PMID- 25387700
TI  - Genome-wide scans of genetic variants for psychophysiological endophenotypes:
      introduction to this special issue of Psychophysiology.
AB  - This special issue addresses the heritability and molecular genetic basis of 17
      putative endophenotypes involving resting EEG power, P300 event-related potential
      amplitude, electrodermal orienting and habituation, antisaccade eye tracking, and
      affective modulation of the startle eye blink. These measures were collected from
      approximately 4,900 twins and parents who provided DNA samples through their
      participation in the Minnesota Twin Family Study. Included are papers that detail
      the methodology followed, genome-wide association analyses of single nucleotide
      polymorphisms and genes, analysis of rare variants in the human exome, and a
      whole genome sequencing study. Also included are 11 articles by leading experts
      in psychophysiology and genetics that provide perspective and commentary. A final
      integrative report summarizes findings and addresses issues raised. This
      introduction provides an overview of the aims and rationale behind these studies.

PMID- 25387699
TI  - Systemic levels of neuropeptide Y and dipeptidyl peptidase activity in patients
      with Ewing sarcoma--associations with tumor phenotype and survival.
AB  - BACKGROUND: Ewing sarcoma (ES) is driven by fusion of the Ewing sarcoma
      breakpoint region 1 gene (EWSR1) with an E26 transformation-specific (ETS)
      transcription factor (EWS-ETS), most often the Friend leukemia integration 1
      transcription factor (FLI1). Neuropeptide Y (NPY) is an EWS-FLI1 transcriptional
      target; it is highly expressed in ES and exerts opposing effects, ranging from ES
      cell death to angiogenesis and cancer stem cell propagation. The functions of NPY
      are regulated by dipeptidyl peptidase IV (DPPIV), a hypoxia-inducible enzyme that
      cleaves the peptide and activates its growth-promoting actions. The objective of
      this study was to determine the clinically relevant functions of NPY by
      identifying the associations between patients' ES phenotype and their NPY
      concentrations and DPP activity. METHODS: NPY concentrations and DPP activity
      were measured in serum samples from 223 patients with localized ES and 9 patients
      with metastatic ES provided by the Children's Oncology Group. RESULTS: Serum NPY
      levels were elevated in ES patients compared with the levels in a healthy control
      group and an osteosarcoma patient population, and the elevated levels were
      independent of EWS-ETS translocation type. Significantly higher NPY
      concentrations were detected in patients with ES who had tumors of pelvic and
      bone origin. A similar trend was observed in patients with metastatic ES. There
      was no effect of NPY on survival in patients with localized ES. DPP activity in
      sera from patients with ES did not differ significantly from that in healthy
      controls and patients with osteosarcoma. However, high DPP levels were associated
      with improved survival. CONCLUSIONS: Systemic NPY levels are elevated in patients
      with ES, and these high levels are associated with unfavorable disease features.
      DPPIV in serum samples from patients with ES is derived from nontumor sources,
      and its high activity is correlated with improved survival.

PMID- 25387701
TI  - Molecular genetic psychophysiology: a perspective on the Minnesota contribution.
AB  - Progress in molecular genetic psychophysiology, on display in this special issue,
      shows that the affective and cognitive processes tagged by psychophysiological
      endophenotypes are highly polygenic. Identifying overlap in the genetic variants
      that influence these endophenotypes as well as behavioral traits can help us
      understand where in the brain, in which stage, and during what type of
      information processing these variants play a role in normal and abnormal
      behavior. The Minnesota Twin Family Study has demonstrated that the assessment of
      genetic markers and extensive psychophysiological experimentation can be done at
      a genetic epidemiological scale, that is, in thousands of subjects. A genome-wide
      association meta-analysis consortium consisting of psychophysiological research
      teams following the Minnesotan example is the obvious next step. 

PMID- 25387702
TI  - Translating intermediate phenotypes to psychopathology: the NIMH Research Domain
      Criteria.
AB  - The Research Domain Criteria project (RDoC) was initiated by the National
      Institute of Mental Health in early 2009 to "develop, for research purposes, new
      ways of classifying mental disorders based on dimensions of observable behavior
      and neurobiological measures." RDoC provides a framework for psychopathology
      research intended to explicate specific aspects of functional impairment by
      studying relevant brain-behavior relationships, in contrast to the current
      heterogeneous categories of mental disorders defined by various groupings of
      symptoms. Endophenotypes fit naturally into the RDoC context since they are
      typically conceived to be closer to fundamental neural and psychological
      mechanisms than more abstracted disorder categories. Consequently, the genomic
      aspects of endophenotypes take on particular significance for understanding
      genetic risk architectures in such an approach to psychopathology. 

PMID- 25387703
TI  - Genome-wide scans of genetic variants for psychophysiological endophenotypes: a
      methodological overview.
AB  - This article provides an introductory overview of the investigative strategy
      employed to evaluate the genetic basis of 17 endophenotypes examined as part of a
      20-year data collection effort from the Minnesota Center for Twin and Family
      Research. Included are characterization of the study samples, descriptive
      statistics for key properties of the psychophysiological measures, and rationale
      behind the steps taken in the molecular genetic study design. The statistical
      approach included (a) biometric analysis of twin and family data, (b)
      heritability analysis using 527,829 single nucleotide polymorphisms (SNPs), (c)
      genome-wide association analysis of these SNPs and 17,601 autosomal genes, (d)
      follow-up analyses of candidate SNPs and genes hypothesized to have an
      association with each endophenotype, (e) rare variant analysis of nonsynonymous
      SNPs in the exome, and (f) whole genome sequencing association analysis using 27
      million genetic variants. These methods were used in the accompanying empirical
      articles comprising this special issue, Genome-Wide Scans of Genetic Variants for
      Psychophysiological Endophenotypes. 

PMID- 25387704
TI  - Heritability and molecular-genetic basis of resting EEG activity: a genome-wide
      association study.
AB  - Several EEG parameters are potential endophenotypes for different psychiatric
      disorders. The present study consists of a comprehensive behavioral- and
      molecular-genetic analysis of such parameters in a large community sample (N =
      4,026) of adolescent twins and their parents, genotyped for 527,829 single
      nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49
      to .85, with a median of .78. The additive effect of all SNPs (SNP heritability)
      varied across electrodes. Although individual SNPs were not significantly
      associated with EEG parameters, several genes were associated with delta power.
      We also obtained an association between the GABRA2 gene and beta power (p <
      .014), consistent with findings reported by others, although this did not survive
      Bonferroni correction. If EEG parameters conform to a largely polygenic model of
      inheritance, larger sample sizes will be required to detect individual variants
      reliably.

PMID- 25387706
TI  - Heritability and molecular genetic basis of electrodermal activity: a genome-wide
      association study.
AB  - The molecular genetic basis of electrodermal activity (EDA) was analyzed using
      527,829 single nucleotide polymorphisms (SNPs) in a large population
      representative sample of twins and parents (N = 4,424) in relation to various EDA
      indices. Biometric analyses suggested that approximately 50% or more of variance
      in all EDA indices was heritable. The combined effect of all SNPs together
      accounted for a significant amount of variance in each index, affirming their
      polygenic basis and heritability. However, none of the SNPs were genome-wide
      significant for any EDA index. Previously reported SNP associations with
      disorders such as substance dependence or schizophrenia, which have been linked
      to EDA abnormalities, were not significant; nor were associations between EDA and
      genes in specific neurotransmitter systems. These results suggest that EDA is
      influenced by multiple genes rather than by polymorphisms with large effects.

PMID- 25387705
TI  - Heritability and molecular-genetic basis of the P3 event-related brain potential:
      a genome-wide association study.
AB  - P3 amplitude is a candidate endophenotype for disinhibitory psychopathology,
      psychosis, and other disorders. The present study is a comprehensive analysis of
      the behavioral- and molecular-genetic basis of P3 amplitude and a P3 genetic
      factor score in a large community sample (N = 4,211) of adolescent twins and
      their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs).
      Biometric models indicated that as much as 65% of the variance in each measure
      was due to additive genes. All SNPs in aggregate accounted for approximately 40%
      to 50% of the heritable variance. However, analyses of individual SNPs did not
      yield any significant associations. Analyses of individual genes did not confirm
      previous associations between P3 amplitude and candidate genes but did yield a
      novel association with myelin expression factor 2 (MYEF2). Main effects of
      individual variants may be too small to be detected by GWAS without larger
      samples.

PMID- 25387707
TI  - Heritability and molecular genetic basis of antisaccade eye tracking error rate:
      a genome-wide association study.
AB  - Antisaccade deficits reflect abnormalities in executive function linked to
      various disorders including schizophrenia, externalizing psychopathology, and
      neurological conditions. We examined the genetic bases of antisaccade error in a
      sample of community-based twins and parents (N = 4,469). Biometric models showed
      that about half of the variance in the antisaccade response was due to genetic
      factors and half due to nonshared environmental factors. Molecular genetic
      analyses supported these results, showing that the heritability accounted for by
      common molecular genetic variants approximated biometric estimates. Genome-wide
      analyses revealed several SNPs as well as two genes-B3GNT7 and NCL-on Chromosome
      2 associated with antisaccade error. SNPs and genes hypothesized to be associated
      with antisaccade error based on prior work, although generating some suggestive
      findings for MIR137, GRM8, and CACNG2, could not be confirmed. 

PMID- 25387708
TI  - Heritability and molecular genetic basis of acoustic startle eye blink and
      affectively modulated startle response: a genome-wide association study.
AB  - Acoustic startle responses have been studied extensively in relation to
      individual differences and psychopathology. We examined three indices of the
      blink response in a picture-viewing paradigm-overall startle magnitude across all
      picture types, and aversive and pleasant modulation scores-in 3,323 twins and
      parents. Biometric models and molecular genetic analyses showed that half the
      variance in overall startle was due to additive genetic effects. No single
      nucleotide polymorphism was genome-wide significant, but GRIK3 produced a
      significant effect when examined as part of a candidate gene set. In contrast,
      emotion modulation scores showed little evidence of heritability in either
      biometric or molecular genetic analyses. However, in a genome-wide scan, PARP14
      produced a significant effect for aversive modulation. We conclude that, although
      overall startle retains potential as an endophenotype, emotion-modulated startle
      does not. 

PMID- 25387711
TI  - Do our "big data" in genetic analysis need to get bigger?
AB  - Individual papers in this special issue might seem disappointing in their lack of
      discovery of specific genes of potential relevance to mental disorders. Yet,
      collectively, they yield information that could not be gleaned otherwise.
      Combining genome-wide complex trait analysis and classic approaches to estimate
      heritability in the same sample, and supplementing genome-wide association
      studies of common variants with exome and sequencing analyses, provides an
      unprecedented opportunity to examine major issues encountered in genetic research
      of complex traits, in ways not easily done with a series of unrelated studies
      using different samples, measures, and analytical approaches. Extending molecular
      genetic approaches to fully multivariate analyses will be an important future
      direction. These will require bigger analyses of even bigger big data, but will
      be essential in efforts to redefine psychopathology in the Research Domain
      Criteria (RDoC) approach promoted in the NIMH strategic plan. 

PMID- 25387709
TI  - Genetic associations of nonsynonymous exonic variants with psychophysiological
      endophenotypes.
AB  - We mapped ~85,000 rare nonsynonymous exonic single nucleotide polymorphisms
      (SNPs) to 17 psychophysiological endophenotypes in 4,905 individuals, including
      antisaccade eye movements, resting EEG, P300 amplitude, electrodermal activity,
      affect-modulated startle eye blink. Nonsynonymous SNPs are predicted to directly
      change or disrupt proteins encoded by genes and are expected to have significant
      biological consequences. Most such variants are rare, and new technologies can
      efficiently assay them on a large scale. We assayed 247,870 mostly rare SNPs on
      an Illumina exome array. Approximately 85,000 of the SNPs were polymorphic, rare
      (MAF < .05), and nonsynonymous. Single variant association tests identified a SNP
      in the PARD3 gene associated with theta resting EEG power. The sequence kernel
      association test, a gene-based test, identified a gene PNPLA7 associated with
      pleasant difference startle, the difference in startle magnitude between pleasant
      and neutral images. No other single nonsynonymous variant, or gene-based group of
      variants, was strongly associated with any endophenotype. 

PMID- 25387710
TI  - In search of rare variants: preliminary results from whole genome sequencing of
      1,325 individuals with psychophysiological endophenotypes.
AB  - Whole genome sequencing was completed on 1,325 individuals from 602 families,
      identifying 27 million autosomal variants. Genetic association tests were
      conducted for those individuals who had been assessed for one or more of 17
      endophenotypes (N range = 802-1,185). No significant associations were found.
      These 27 million variants were then imputed into the full sample of individuals
      with psychophysiological data (N range = 3,088-4,469) and again tested for
      associations with the 17 endophenotypes. No association was significant. Using a
      gene-based variable threshold burden test of nonsynonymous variants, we obtained
      five significant associations. These findings are preliminary and call for
      additional analysis of this rich sample. We argue that larger samples,
      alternative study designs, and additional bioinformatics approaches will be
      necessary to discover associations between these endophenotypes and genomic
      variation.

PMID- 25387712
TI  - Genomic substrates of neurophysiological endophenotypes: where we've been and
      where we're going.
AB  - This special issue of Psychophysiology is focused on an imaginative and labor
      intensive examination of the genomic substrates of heritable neurophysiological
      endophenotypes in the Minnesota Center for Twin and Family Research (MCTFR)
      cohorts. The authors artfully combine the power of family-based behavioral data
      with the atheoretical genome-wide association study (GWAS) platform to enrich the
      examination of the genomic substrates of endophenotypes. Neurophysiological
      endophenotype deficits are found in psychiatric patients and are heritable in
      families of these psychiatric patients, allowing the investigators to combine the
      explanatory power of endophenotypes, with their known neural and functional
      substrates, with the otherwise agnostic identification of genes in the GWAS
      platform. This amplifies the power of the MCTFR endophenotype database. These
      well-considered studies add significantly to our understanding of normal human
      neurobiology and stimulate the use of these endophenotypes to expand our
      knowledge of the role of these measures and their genomic substrates in normal
      and psychopathology research. 

PMID- 25387713
TI  - Decomposing P300 to identify its genetic basis.
AB  - In this commentary, I explore reasons why it has been difficult to associate P300
      amplitude with a gene or a single nucleotide polymorphism (SNP). I suggest we
      decompose P300 into the factors that contribute to it to get better traction on
      its genetic basis. Specifically, I note that we can improve the measurement of
      P300 to remove state-dependent contributions by including more than one
      measurement occasion; we can identify and extract the neural components
      contributing to P300 amplitude by estimating EEG power in specific bands of the
      P300; we can adjust P300 for single-trial variability; we can extract single
      trial variability; and we can refine the tasks to isolate the separate
      psychological processes that P300 reflects. In the end, each of these factors
      that contribute to the conglomerate P300 may be a separate endophenotype mapping
      onto a separate SNP or gene. 

PMID- 25387714
TI  - The missing heritability of behavior: the search continues.
AB  - Genetic variation altering behavior is elusive. This commentary discusses
      implications for the search for "missing heritability" posed by a unified series
      of studies from the Minnesota Center for Twin and Family Research. Endophenotypes
      are measured in a longitudinal cohort including twins, analyzed for heritability
      and genetically mapped via genome-wide association and genome sequencing. The
      genes identified account for a fraction of the heritability, but the manner in
      which the studies were conducted points to explanations other than methodology.
      The MCTFR data are an unprecedented addition to the research information commons.
      Other gene discoveries will follow when they are analyzed in new ways and in
      combination with other studies. Even larger samples may be needed. Alternatively
      or in addition, locus identification, especially rare alleles, may require the
      study of families and population isolates with founder characteristics. 

PMID- 25387715
TI  - Hunting genes, hunting endophenotypes.
AB  - Identifying specific genetic contributions to psychopathology has proved to be
      much more difficult than anticipated. In pursuit of this goal, Iacono and
      colleagues provide a remarkable set of studies that are important for the methods
      showcased as well as the findings reported. The immediate yield of positive
      findings is somewhat limited, but such an outcome is in fact quite informative.
      These papers will inspire further innovation and ambition in efforts to identify
      causal pathways to psychopathology and, more specifically, will increase emphasis
      on endophenotypes, a perspective highly compatible with the NIMH Research Domain
      Criteria (RDoC) initiative. 

PMID- 25387716
TI  - The genetic architecture of psychophysiological phenotypes.
AB  - It is now clear that almost all complex traits have a highly polygenic component;
      that is, their genetic basis consists of relatively frequent risk alleles at a
      very large number of loci, each making a small contribution to variation, or
      disease susceptibility. This general conclusion appears to hold for intermediate
      phenotypes. Therefore, we should not expect these phenotypes to be associated
      with substantially larger effect sizes than conventional phenotypes. Instead,
      their usefulness is likely to lie in understanding the mechanism underpinning
      associations identified via genome-wide association studies of conventional
      phenotypes. 

PMID- 25387717
TI  - Genetics, neuroscience, and psychopathology: clothing the emperor.
AB  - This ground-breaking series of articles reports findings from genome-wide
      analyses of endophenotypic indicators of psychopathology including
      electrocortical activity/reactivity, electrodermal and startle blink responses,
      and neurocognitive task performance. Findings challenge the long-held notion that
      endophenotypes more clearly reflect the impact of specific genes than referent
      clinical phenotypes. Implications for the concept of endophenotypes and
      biological psychopathology research more broadly are discussed. 

PMID- 25387718
TI  - Are we doing enough to extract genomic information from our data?
AB  - Genome-wide studies have been successful in identifying stable associations of
      single genes, albeit at the price of a high false negative rate. The promise of
      endophenotypes to increase power of genome-wide association studies has only been
      partially fulfilled. To optimize the investigation of genetic influences on
      behavioral (endo-)phenotypes, the development of novel phenotypical
      characterizations and methods to describe the relation between genotype and
      phenotype are needed. This will require the development of innovative analytical
      strategies, as well as corroborative approaches linking association studies with
      functional characterizations. The sole reliance on canonical genome-wide
      significance thresholds is not sufficient to describe the complex relation of
      genotype and phenotype. 

PMID- 25387719
TI  - The feasibility of genetic dissection of endophenotypes.
AB  - Endophenotypes are traits that proceed and predict traits of interest. In this
      special issue, there are a series of papers on genomic analysis of 17 physiologic
      traits measured by the Minnesota Center for Twin and Family Research that are
      thought to be endophenotypes for behavioral clinical traits such as addiction and
      schizophrenia. Because these 17 traits, which can be precisely defined and
      measured throughout the life of subjects, display variation in normal subjects
      and are heritable, it is thought that they may be more tractable to genetic
      dissection. These articles show that these 17 endophenotypes appear to have a
      similar architecture to the vast majority of traits with complex modes of
      inheritance. The study identified several genetic loci that play a role in these
      endophenotypes. It appears that further progress in understanding the genetics of
      these 17 endophenotypes can be made with an expanded data set. 

PMID- 25387720
TI  - Knowns and unknowns for psychophysiological endophenotypes: integration and
      response to commentaries.
AB  - We review and summarize seven molecular genetic studies of 17 psychophysiological
      endophenotypes that comprise this special issue of Psychophysiology, address
      criticisms raised in accompanying Perspective and Commentary pieces, and offer
      suggestions for future research. Endophenotypes are polygenic, and possibly
      influenced by rare genetic variants. Because they are not simpler genetically
      than clinical phenotypes, they are unlikely to assist gene discovery for
      psychiatric disorder. Once genetic variants for clinical phenotypes are
      identified, associated endophenotypes are likely to provide valuable insights
      into the psychological and neural mechanisms important to disorder pathology.
      This special issue provides a foundation for informed future steps in
      endophenotype genetics, including the formation of large sample consortia capable
      of fleshing out the many genetic variants contributing to individual differences
      in psychophysiological measures. 

PMID- 25387721
TI  - Operative efficiency and accuracy of patient-specific cutting guides in total
      knee replacement.
AB  - BACKGROUND: Total knee replacement (TKR) outcomes depend on accurate positioning
      of implants and restoration of the mechanical axis of the knee. Compared with
      standard techniques, patient-specific cutting guides are postulated to improve
      accuracy of bone resections, and therefore implant placement. Furthermore,
      patient-specific cutting guides are postulated to reduce operative time and
      increase efficiency by reducing the number of trays used. METHODS: This study
      evaluates these claims using the Visionaire (Smith & Nephew, Inc., Memphis, TN,
      USA) patient-specific system. The thickness of actual bone resections was
      compared with the predicted thickness (giving a resection 'error'). Data were
      also obtained on the number of trays used, skin-to-skin operating time and
      tourniquet time. RESULTS: Forty-one TKRs were performed on 33 females (one
      bilateral) and seven males. Average resection errors were 0.22 mm medially and
      0.05 mm laterally for the distal femur, 0.99 mm medially and 0.74 mm laterally
      for posterior femoral condyles, and 0.55 mm medially and 0.71 mm laterally for
      the proximal tibia. There were no significant differences in tourniquet time,
      skin-to-skin time or the number of trays used between the patient-specific and
      historical comparison groups. CONCLUSION: Patient-specific cutting guides make
      accurate resections. Operative and tourniquet times and the number of trays used
      were no different to standard TKRs. Further investigation is needed to determine
      whether patient-specific cutting guides improve post-operative alignment and
      patient satisfaction.

PMID- 25387722
TI  - 9TH International Conference on Early Psychosis - To the New Horizon, 17 November
      2014, Tokyo Japan.

PMID- 25387723
TI  - Direct comparison of visual and quantitative bone marrow FDG-PET/CT findings with
      bone marrow biopsy results in diffuse large B-cell lymphoma: does bone marrow FDG
      PET/CT live up to its promise?
AB  - BACKGROUND: Detection of bone marrow involvement using 18F-fluoro-2-deoxy-D
      glucose positron emission tomography/computed tomography (FDG-PET/CT) has been
      proposed as a non-invasive alternative to standard blind bone marrow biopsy (BMB)
      of the posterior iliac crest in patients with newly diagnosed diffuse large B
      cell lymphoma (DLBCL). However, studies that directly compare FDG-PET/CT results
      with histopathology are currently lacking. PURPOSE: To directly compare both
      visual and quantitative bone marrow FDG-PET/CT to BMB at the right posterior
      iliac crest in patients with newly diagnosed DLBCL. MATERIAL AND METHODS: A total
      of 40 patients with newly diagnosed DLBCL, who had undergone FDG-PET/CT before
      BMB of the right posterior iliac crest, were retrospectively included. FDG-PET/CT
      images were visually assessed for bone marrow involvement in the right posterior
      iliac crest. 3D partial volume corrected mean standardized uptake value
      (cSUVmean), maximum standardized uptake value (SUVmax), and peak standardized
      uptake value (SUVpeak) were measured in the right posterior iliac crest, using
      volume of interest analysis. BMB of the right posterior iliac crest was used as
      reference standard for bone marrow involvement. RESULTS: Sensitivity and
      specificity of visual FDG-PET/CT analysis for the detection of bone marrow
      involvement in the right posterior iliac crest were 14.3% (95% confidence
      interval [CI], 0.5-53.4%) and 100% (95% CI, 87.6-100%), respectively. cSUVmean,
      SUVmax, and SUVpeak of BMB-negative patients (1.4 +/- 0.49, 2.2 +/- 0.69, and 1.7
      +/- 0.59, respectively) considerably overlapped with those of BMB-positive
      patients (1.8 +/- 0.53, 2.7 +/- 0.71, and 2.2 +/- 0.61, respectively).
      CONCLUSION: In a local, head-to-head comparison with BMB, the diagnostic value of
      both visual and quantitative FDG-PET/CT for the detection of bone marrow
      involvement is low in patients with newly diagnosed DLBCL.

PMID- 25387725
TI  - Bowen's disease with features resembling myrmecia wart.
AB  - We report the clinical and pathological findings of two cases of Bowen's disease
      (BD) with features resembling myrmecia wart, and tried to find evidence of human
      papillomavirus (HPV) infection in such lesions by immunohistological staining,
      genotyping systems, polymerase chain reaction (PCR) and electron microscopy. Both
      cases manifested unique barnacle-like hyperkeratotic nodules or plaques
      clinically, and microscopically proliferation of atypical keratinocytes involving
      the entire thickness of the epidermis, hypergranulosis with eosinophilic and/or
      basophilic inclusion bodies, features that mimicked myrmecia wart. Electron
      microscopy revealed myrmecia inclusion-like large intranuclear and cytoplasmic
      electron-dense bodies. Immunohistological staining with anti-HPV antibody,
      genotyping systems for HPV infection and specific PCR designed to detect HPV-1 L1
      sequences failed to detect evidence of HPV infection. P16(INK4a) was
      overexpressed in the atypical keratinocytes of both cases. This finding suggests
      that the pathogenesis of these two BD may involve certain unknown or undetectable
      HPV, or reflect disturbances of the Rb signaling pathway unrelated to HPV
      infection. The unique "myrmecioid" clinicopathological features in our cases
      suggest that this type of lesion may be a new variant of BD. 

PMID- 25387724
TI  - Immunological effects and therapeutic role of C5a in cancer.
AB  - The specific role of C5a in cancer, especially in melanoma, has yet to be
      determined. Differential effects of C5a could be cancer specific. In the host
      defense system, C5a functions to protect the body from harmful entities via a
      plethora of mechanisms. Yet, C5a may also serve to potentiate cancerous process.
      C5a facilitates cellular proliferation and regeneration by attracting myeloid
      derived suppressor cells and supporting tumor promotion. In this article, we
      critically reviewed the properties, mechanisms of action and functions of C5a,
      with particular emphasis on cancer inhibition and promotion, and clinical
      application of such knowledge in better management of patients with cancer.
      Outstanding questions and future directions in regard to the function of C5a in
      melanoma and other cancers are discussed. 

PMID- 25387726
TI  - The application of connected QSRR and QSAR strategies to predict the
      physicochemical interaction of acridinone derivatives with DNA.
AB  - Acridinone derivatives as imidazoacridinones and triazoloacridinones are the new
      potent antitumor agents characterized by different mechanisms of action related
      to their ability to interact with DNA. The analysis undertaken in this study
      involves searching of QSAR (Quantitative Structure-Activity Relationship) and
      QSRR (Quantitative Structure- Retention Relationship) models, which would allow
      to predict the biological activity of acridinones expressed as the ability to
      stabilize the secondary structure of DNA (DeltaT), based on their structural
      parameters and chromatographic retention data. For this purpose, 20 acridinone
      derivatives were subjected to chromatographic analyses and molecular modeling,
      followed by statistical analyses using multiple linear regression method (MLR).
      As a novelty aspect, except for RP-HPLC approach, hydrophilic interaction
      chromatography (HILIC) columns were tested. As a result of performed analysis,
      appropriate QSAR and QSRR models were obtained, and each model was analyzed in
      terms of prediction of acridinones' ability to interact with DNA. Derived QSAR
      and QSRR models were characterized as one, with good prediction performance.
      Conclusively, the proposed connected QSAR and QSRR strategies allow to predict in
      silico the ability of acridinones to interact with DNA without the necessity of
      performing any biological experiments under in vitro and in vivo conditions. 

PMID- 25387727
TI  - Renal function after low central venous pressure-assisted liver resection:
      assessment of 2116 cases.
AB  - OBJECTIVES: Low central venous pressure (LCVP)-assisted hepatectomy is associated
      with decreased blood loss and lower transfusion rates. Concerns about its impact
      on renal function have prevented widespread application. This study was conducted
      to review the dynamics of renal function after LCVP-assisted hepatectomy.
      METHODS: A retrospective analysis of a prospective surgical database was carried
      out. Estimated glomerular filtration rate (eGFR) was calculated using the
      Modification of Diet in Renal Disease (MDRD) equation. The RIFLE (risk-injury
      failure-loss-end-stage) criteria were used to define postoperative biochemical
      acute kidney injury (bAKI). Occurrences of clinically relevant AKI (cAKI) were
      identified in the study center postoperative database. RESULTS: During the period
      2003-2012, 2116 LCVP-assisted hepatectomies were performed. The median patient
      age was 61 years [interquartile range (IQR): 51-70 years] and 51% of patients
      were male. The median number of resected segments was two; resections involved
      from one to four segments. Median estimated blood loss was 300 ml (IQR: 200-600
      ml). Rates of morbidity and 90-day mortality were 21% and 2%, respectively. Low
      baseline eGFR (<90 ml/min) was seen in 84% of patients; 29% of patients had eGFR
      of <30 ml/min. Postoperative bAKI was seen in 17% (n = 350) of patients.
      Biochemical AKI with low eGFR was seen in 336 patients, representing 16% of the
      whole cohort; 13% of patients had been at risk, 2% experienced injury and 1%
      experienced failure. Kidney function had normalized at discharge in 159 of these
      patients. Nine patients (<1%) developed postoperative cAKI. CONCLUSIONS: The
      majority of patients in the study cohort had low baseline eGFR. Biochemical
      alterations in eGFR are transient in the vast majority of patients after LCVP
      assisted hepatectomy and their clinical impact is limited. The present data
      suggest that clinically relevant renal dysfunction is a very uncommon event in
      patients undergoing LCVP-assisted liver resection.

PMID- 25387729
TI  - Ability versus hazard: risk-taking and falls in older people.
AB  - BACKGROUND: Among older people, undue risk taking could lead to falls,
      irrespective of physical ability. We investigated the interaction between risk
      taking behavior and physical ability and its contribution to falls. METHODS:
      Participants (N = 294, age >= 70) were asked to walk as quickly as possible to a
      visible destination by choosing one of six paths. Each contained a raised plank
      that had to be walked along without falling. The shortest path had the narrowest
      and tallest plank and the longest had the widest and lowest. Behavioral risk was
      defined as the probability of falling off the chosen plank. This was estimated
      from a ground path walking task because, for safety, participants were stopped
      before crossing the plank. Self-reported everyday risk-taking behavior, fear of
      falling, physical functioning, and 1-year prospective fall rates were measured.
      RESULTS: Older participants and those with poor physical ability chose easier
      planks to cross. Participants with good physical ability consistently took a
      slight behavioral risk, whereas those with poor physical ability took either very
      high behavioral risks or chose the overly safe path with no risk. Unexpectedly,
      participants reporting cautious behavior on the everyday risk-taking behavior
      scale took greater behavioral risks. Independent of physical performance,
      behavioral risk was significantly associated with falls during the subsequent
      year. CONCLUSIONS: Assessing behavioral choice in relation to physical ability
      can identify risk-taking but neither the difficulty of a chosen action nor self
      reports of risk-taking behavior are sufficient. Risk-taking behavior is an
      independent risk factor for falls and management of undue risk-taking might
      complement existing fall prevention strategies.

PMID- 25387728
TI  - A physical activity intervention to treat the frailty syndrome in older persons
      results from the LIFE-P study.
AB  - BACKGROUND: The frailty syndrome is as a well-established condition of risk for
      disability. Aim of the study is to explore whether a physical activity (PA)
      intervention can reduce prevalence and severity of frailty in a community
      dwelling elders at risk of disability. METHODS: Exploratory analyses from the
      Lifestyle Interventions and Independence for Elders pilot, a randomized
      controlled trial enrolling 424 community-dwelling persons (mean age=76.8 years)
      with sedentary lifestyle and at risk of mobility disability. Participants were
      randomized to a 12-month PA intervention versus a successful aging education
      group. The frailty phenotype (ie, >=3 of the following defining criteria:
      involuntary weight loss, exhaustion, sedentary behavior, slow gait speed, poor
      handgrip strength) was measured at baseline, 6 months, and 12 months. Repeated
      measures generalized linear models were conducted. RESULTS: A significant (p =
      .01) difference in frailty prevalence was observed at 12 months in the PA
      intervention group (10.0%; 95% confidence interval = 6.5%, 15.1%), relative to
      the successful aging group (19.1%; 95% confidence interval = 13.9%,15.6%). Over
      follow-up, in comparison to successful aging participants, the mean number of
      frailty criteria in the PA group was notably reduced for younger subjects,
      blacks, participants with frailty, and those with multimorbidity. Among the
      frailty criteria, the sedentary behavior was the one most affected by the
      intervention. CONCLUSIONS: Regular PA may reduce frailty, especially in
      individuals at higher risk of disability. Future studies should be aimed at
      testing the possible benefits produced by multidomain interventions on frailty.

PMID- 25387730
TI  - Carotid stenting and intracranial thrombectomy for treatment of acute stroke due
      to tandem occlusions with aggressive antiplatelet therapy may be associated with
      a high incidence of intracranial hemorrhage.
AB  - BACKGROUND: Acute stroke from tandem extracranial carotid artery and intracranial
      large vessel occlusion poses challenges for emergency endovascular treatment.
      Establishing and maintaining patency of the carotid artery and avoiding
      intracranial hemorrhage are competing concerns. METHODS: Twenty-three consecutive
      cases of emergency carotid stenting followed by mechanical thrombectomy
      identified by retrospective review of the endovascular ischemic stroke database
      maintained prospectively at our institution since January 2011 form the basis for
      this report. No cases were lost to follow-up. RESULTS: Patients were selected
      with CT angiography or MR angiography and diffusion weighted imaging. Carotid
      stenting was successful in all cases, and establishment of Thrombolysis in
      Cerebral Ischemia 2A, 2B or 3 flow was successful in 21/23 (91%). 12/23 (52%)
      patients achieved a modified Rankin Scale score of 0-2 at 90 days. Symptomatic
      intracranial hemorrhage (SICH) occurred in 5/23 patients (22%). Of 13 patients
      receiving an intravenous loading dose of abciximab during the procedure, 4/13 had
      SICH (31%) compared with 1/10 (10%) of those who did not. Of seven patients who
      received intravenous tissue plasminogen activator prior to the procedure, none
      had SICH. 90-day mortality was 9/23 (39%). All patients who had SICH were above
      the median age. CONCLUSIONS: Primary stenting of the extracranial carotid artery
      combined with intracranial mechanical thrombectomy can be an effective treatment
      for tandem occlusions, can be performed with a high rate of technical success,
      and can achieve good clinical outcomes in selected patients. However, the
      incidence of SICH may be higher than in other patient populations and may be
      associated with the use of abciximab and advanced patient age.

PMID- 25387731
TI  - Relationship between aneurysm occlusion and flow diverting device oversizing in a
      rabbit model.
AB  - BACKGROUND AND PURPOSE: Implanted, actual flow diverter pore density is thought
      to be strongly influenced by proper matching between the device size and parent
      artery diameter. The objective of this study was to characterize the correlation
      between device sizing, metal coverage, and the resultant occlusion of aneurysms
      following flow diverter treatment in a rabbit model. METHODS: Rabbit saccular
      aneurysms were treated with flow diverters (iso-sized to proximal parent artery,
      0.5 mm oversized, or 1.0 mm oversized, respectively, n=6 for each group). Eight
      weeks after implantation, the angiographic degree of aneurysm occlusion was
      graded (complete, near-complete, or incomplete). The ostium of the explanted
      aneurysm covered with the flow diverter struts was photographed. Based on gross
      anatomic findings, the metal coverage and pore density at the ostium of the
      aneurysm were calculated and correlated with the degree of aneurysm occlusion.
      RESULTS: Angiographic results showed there were no statistically significant
      differences in aneurysm geometry and occlusion among groups. The mean parent
      artery diameter to flow diverter diameter ratio was higher in the 1.0 mm
      oversized group than in the other groups. Neither the percentage metal coverage
      nor the pore density showed statistically significant differences among groups.
      Aneurysm occlusion was inversely correlated with the ostium diameter,
      irrespective of the size of the device implanted. CONCLUSIONS: Device sizing
      alone does not predict resultant pore density or metal coverage following flow
      diverter implantation in the rabbit aneurysm model. Aneurysm occlusion was not
      impacted by either metal coverage or pore density, but was inversely correlated
      with the diameter of the ostium.

PMID- 25387732
TI  - Systematic lymphadenectomy in the treatment of epithelial ovarian cancer: a meta
      analysis of multiple epidemiology studies.
AB  - OBJECTIVE: To evaluate the role of systematic lymphadenectomy in epithelial
      ovarian cancer by comparing 5-year overall survival rates between systematic and
      unsystematic lymphadenectomies. METHODS: A literature search of the Pubmed,
      Embase and Cochrane Library databases was performed up to 2014. Two authors
      independently determined the eligibility of the articles and extracted the
      available data. The role of systematic lymphadenectomy in epithelial ovarian
      cancer was analyzed by combining all qualified individual studies using a fixed
      effect model. Then, subgroup analysis was performed by dividing articles
      according to type, cancer stage and residual tumor. Finally, heterogeneity and
      publication bias in all enrolled studies were assessed using Higgins I(2)
      statistics and funnel plots, respectively. RESULTS: Fourteen relevant studies
      including 3488 subjects were included in the analysis. The value of pooled
      relative ratios of all qualified studies revealed that the 5-year overall
      survival rate in the lymphadenectomy group was higher than that in the
      unsystematic lymphadenectomy group (relative ratio = 1.08; P = 0.001), which was
      duplicated in the subgroup analysis of observational studies (relative ratio =
      1.07; P = 0.002) and advanced stage (relative ratio = 1.21; P = 0.012) epithelial
      ovarian cancer. No significant differences were observed in randomized controlled
      trials (relative ratio = 1.01; P = 0.858), early stage epithelial ovarian cancer
      (relative ratio = 1.06; P = 0.064) or patients with residual tumor <=2 cm
      (relative ratio = 1.05; P = 0.125). The heterogeneity and publication bias in the
      enrolled studies were within acceptable thresholds. CONCLUSIONS: Lymphadenectomy
      can improve the 5-year overall survival rate in advanced stage epithelial ovarian
      cancer but not in early stage epithelial ovarian cancer or in patients with
      residual tumor <=2 cm.

PMID- 25387733
TI  - Comparison of the clinical and prognostic features of primary breast sarcomas and
      malignant phyllodes tumor.
AB  - OBJECTIVE: Primary breast sarcoma is a kind of extremely rare disease. Malignant
      phyllodes tumor represents a specific subset of breast soft tissue tumors. So
      till now, the classification and clinical management of primary breast sarcoma
      and malignant phyllodes tumor are controversial. The aim of this study is to
      explore the differences in clinical features, treatment, disease-free survival
      and overall survival between primary breast sarcoma and malignant phyllodes tumor
      group. METHODS: A retrospective review of 35 cases with primary breast sarcoma
      and 70 cases with malignant phyllodes tumor registered from 1995 to 2010 was
      carried out in Tianjin Medical University Cancer Institute and Hospital.
      Prognosis in terms of disease-free survival and overall survival was evaluated.
      RESULTS: In primary breast sarcoma group, the result of univariate analysis
      demonstrated that surgical type, histopathological nodal status and local
      recurrence were significantly correlated with disease-free survival and overall
      survival. While, the result of monofactorial analysis showed the tumor size was
      significant prognostic indicator of disease-free survival and overall survival in
      malignant phyllodes tumor group. The Kaplan-Meier curves for 5-year disease-free
      survival rates and overall survival rates demonstrated that no significant
      difference was found between the primary breast sarcoma and malignant phyllodes
      tumor group (P = 0.702 and 0.772, respectively). CONCLUSIONS: The primary breast
      sarcoma patients had identical disease-free survival and overall survival
      compared with the malignant phyllodes tumor patients, which indicated that
      primary breast sarcoma and malignant phyllodes tumor patients should be treated
      with the same strategies. Surgical management is important for both the primary
      breast sarcoma and malignant phyllodes tumor patients. The role of the adjuvant
      radiotherapy and chemotherapy remains uncertain.

PMID- 25387734
TI  - [Animal tumour registry: limitations and potentials].

PMID- 25387735
TI  - [Reply: similarities between human and animal cancer registries].

PMID- 25387737
TI  - [Reply].

PMID- 25387736
TI  - [Tobacco taxation is a public health measure].

PMID- 25387738
TI  - [Arsenic in drinking water: some considerations of the authors of the SEpiAs
      Project].

PMID- 25387739
TI  - [Towards a correct waste management policy in Italy].

PMID- 25387740
TI  - [The future of epidemiology for environment, health, and equity. 38th Congress of
      the Italian Association of Epidemiology].

PMID- 25387741
TI  - [Health systems: public may be not only effective, but also efficient].

PMID- 25387742
TI  - [Citizens' veillance on environmental health through ICT and Genomics].
AB  - In the last decade three different phenomena have merged: the widespread use of
      ICT devices to collect and potentially share personal and scientific data, and to
      build networked communities; biobanking for genomics, namely the organized
      storage of human biological samples and information; and the collaboration
      between scientists and citizens in creating knowledge, namely peer-production of
      knowledge, for shared social goals. These different forms of knowledge, technical
      tools, and skills have merged in community based scientific and social, as well
      as legal, initiatives, where scientists and citizens use genetic information and
      ICT as powerful ways to gain more control over their health and the environment.
      These activities can no longer be simply qualified as epidemiological research
      and surveillance. Instead, they can be framed as new forms of citizens'
      participatory "veillance:" an attitude of cognitive proactive alertness towards
      the protection of common goods. This paper illustrates two Italian case-studies
      where citizens and scientists, by making use of both ICT and biobanking, have
      joined with the goal of protecting environmental health in highly polluted
      contexts. The statute of these initiatives still needs to be defined as to both
      the validity of the underlying citizen science and the lack of adequate legal
      tools for structuring them. However, as to their scientific quality and use of
      sophisticated technologies, these activities cannot be compared to previous
      experiences, such as those inspired by so-called popular epidemiology. Moreover,
      the deep awareness towards the data to be transparent, reliable, and accessible,
      as well as towards funding mechanisms to be crowdsourced, allows these
      experiences to go beyond the mere confrontation with institutional knowledge, and
      to represent a potential model for knowledge production for institutional
      implementation. 

PMID- 25387743
TI  - [EpiChange: not only environment. Patients' participation changes the world of
      trials].

PMID- 25387744
TI  - [Healthcare and wastes: research, public health and communication].

PMID- 25387745
TI  - [Methods for health impact assessment of policies for municipal solid waste
      management: the SESPIR Project].
AB  - The Project Epidemiological Surveillance of Health Status of Resident Population
      Around the Waste Treatment Plants (SESPIR) included five Italian regions (Emilia
      Romagna, Piedmont, Lazio, Campania, and Sicily) and the National Institute of
      Health in the period 2010-2013. SESPIR was funded by the Ministry of Health as
      part of the National centre for diseases prevention and control (CCM) programme
      of 2010 with the general objective to provide methods and operational tools for
      the implementation of surveillance systems for waste and health, aimed at
      assessing the impact of the municipal solid waste (MSW) treatment cycle on the
      health of the population. The specific objective was to assess health impacts
      resulting from the presence of disposal facilities related to different regional
      scenarios of waste management. Suitable tools for analysis of integrated
      assessment of environmental and health impact were developed and applied, using
      current demographic, environmental and health data. In this article, the
      methodology used for the quantitative estimation of the impact on the health of
      populations living nearby incinerators, landfills and mechanical biological
      treatment plants is showed, as well as the analysis of three different temporal
      scenarios: the first related to the existing plants in the period 2008-2009
      (baseline), the second based on regional plans, the latter referring to MSW
      virtuous policy management based on reduction of produced waste and an intense
      recovery policy. 

PMID- 25387746
TI  - [Health impact assessment of policies for municipal solid waste management:
      findings of the SESPIR Project].
AB  - The SESPIR Project (Epidemiological Surveillance of Health Status of Resident
      Population Around the Waste Treatment Plants) assessed the impact on health of
      residents nearby incinerators, landfills and mechanical biological treatment
      plants in five Italian regions (Emilia-Romagna, Piedmont, Lazio, Campania, and
      Sicily). The assessment procedure took into account the available knowledge on
      health effects of waste disposal facilities. Analyses were related to three
      different scenarios: a Baseline scenario, referred to plants active in 2008-2009;
      the regional future scenario, with plants expected in the waste regional plans; a
      virtuous scenario (Green 2020), based on a policy management of municipal solid
      waste (MSW) through the reduction of production and an intense recovery policy.
      Facing with a total population of around 24 million for the 5 regions, the
      residents nearby the plants were more than 380,000 people at Baseline. Such a
      population is reduced to approximately 330.000 inhabitants and 170.000
      inhabitants in the regional and Green 2020 scenarios, respectively. The health
      impact was assessed for the period 2008-2040. At Baseline, 1-2 cases per year of
      cancer attributable to MSW plants were estimated, as well as 26 cases per year of
      adverse pregnancy outcomes (including low birth weight and birth defects), 102
      persons with respiratory symptoms, and about a thousand affected from annoyance
      caused by odours. These annual estimates are translated into 2,725 years of life
      with disability (DALYs) estimated for the entire period. The DALYs are reduced by
      approximately 20% and 80% in the two future scenarios. Even in these cases,
      health impact is given by the greater effects on pregnancy and the annoyance
      associated with the odours of plants. In spite of the limitations due to the
      inevitable assumptions required by the present exercise, the proposed methodology
      is suitable for a first approach to assess different policies that can be adopted
      in regional planning in the field of waste management. The greatest reduction in
      health impact is achieved with a virtuous policy of reducing waste production and
      a significant increase in the collection and recycling of waste. 

PMID- 25387747
TI  - [Morbidity in a population living close to urban waste incinerator plants in
      Lazio Region (Central Italy): a retrospective cohort study using a before-after
      design].
AB  - BACKGROUND: the body of evidence on health effects of residential exposure to
      urban waste incinerators suggests association with reproductive outcomes and some
      cancers, but the overall evidence is still limited. OBJECTIVES: we evaluated the
      impact of two incinerators on hospital admissions for respiratory and
      cardiovascular diseases in a cohort of people living nearby two incineration
      plants in Lazio Region (Central Italy) using a before-and-after design. METHODS:
      the study area was defined as the 7-km radius around the incinerators. People who
      were resident in the area from 1996 to 2008 were enrolled in a retrospective
      longitudinal study. All addresses were geocoded. A Lagrangian dispersion model
      (SPRAY) for PM10 (ng/m3) was used for incinerators exposure assessment. Average
      annual concentration of background PM10 (MUg/m3) was estimated on a regional
      basis by means of RAMS and FARM models. Both PM10 exposures were estimated at the
      residential address. All subjects were followed for hospital admissions in the
      period before (1996-2002) and after (2003-2008) the activation of the plants. The
      association between exposure to emissions from incinerators and hospitalizations
      in the two periods was estimated using the multivariate Cox model (for repeated
      events), adjusting for age, area-level socioeconomic status, distance from
      industries, traffic roads and highways. An interaction term between the period of
      follow-up (before or after the activation of the plants) and the exposure levels
      was used to test the effect of the incinerators. RESULTS: 47,192 subjects
      resident in the study area were enrolled. No clear association between pollution
      exposure from incinerators and cause-specific morbidity of residents in highest
      concentration areas was found when compared to the reference group. However, an
      effect of PM10 on respiratory diseases and chronic obstructive pulmonary disease
      was suggested. The effect was due to excesses of hospitalizations for the same
      causes among men living in highest exposure areas in respect to the reference
      group (hazard ratio - HR: 1.26; 95%CI 0.99-1.60, and HR: 1.86; 95%CI 1.04-3.33,
      respectively). There were associations between exposure to background pollution
      from other sources and hospitalizations for diseases of the circulatory system
      (HR: 1.08; 95%CI 1.03-1.13) and respiratory diseases (HR: 1.07; 95%CI 1.02-1.11)
      (for a unitary increment of PM10, MUg/m3). CONCLUSIONS: living in areas with high
      PM10 levels due to incinerators was associated with increased morbidity levels
      for respiratory disorders among men. The study area is critical from an
      environmental point of view, hence an epidemiological surveillance is
      recommended.

PMID- 25387748
TI  - [Inverse probability weighting (IPW) for evaluating and "correcting" selection
      bias].
AB  - INTRODUCTION: the Inverse probability weighting (IPW) is a methodology developed
      to account for missingness and selection bias caused by non-randomselection of
      observations, or non-random lack of some information in a subgroup of the
      population. OBJECTIVES: to provide an overview of IPW methodology and an
      application in a cohort study of the association between exposure to traffic air
      pollution (nitrogen dioxide, NO2) and 7-year children IQ. METHOD: this
      methodology allows to correct the analysis by weighting the observations with the
      probability of being selected. The IPW is based on the assumption that individual
      information that can predict the probability of inclusion (non-missingness) are
      available for the entire study population, so that, after taking account of them,
      we can make inferences about the entire target population starting from the
      nonmissing observations alone.The procedure for the calculation is the following:
      firstly, we consider the entire population at study and calculate the probability
      of non-missing information using a logistic regression model, where the response
      is the nonmissingness and the covariates are its possible predictors.The weight
      of each subject is given by the inverse of the predicted probability. Then the
      analysis is performed only on the non-missing observations using a weighted
      model. CONCLUSIONS: IPW is a technique that allows to embed the selection process
      in the analysis of the estimates, but its effectiveness in "correcting" the
      selection bias depends on the availability of enough information, for the entire
      population, to predict the non-missingness probability. In the example proposed,
      the IPW application showed that the effect of exposure to NO2 on the area of
      verbal intelligence quotient of children is stronger than the effect showed from
      the analysis performed without regard to the selection processes.

PMID- 25387749
TI  - Fine-scale genetic differentiation of a temperate herb: relevance of local
      environments and demographic change.
AB  - The genetic structure of a plant species is shaped by environmental adaptation
      and demographic factors, but their relative contributions are still unknown. To
      examine the environment- or geography-related differentiation, we quantified
      genetic variation among 41 populations of a temperate herb, Arabidopsis halleri
      subsp. gemmifera (Brassicaceae). We analysed 19 microsatellite loci, which showed
      a significant population differentiation and a moderate within-population genetic
      diversity (global Gst = 0.42 and Hs = 0.19). Our structure analysis and
      phylogenetic network did not detect more than two genetic groups across the
      Japanese mainland but found fine-scale genetic differentiations and admixed
      patterns around the central area. Across the Japanese mainland, we found
      significant evidence for isolation-by-distance but not for isolation-by
      environments. However, at least within the central area, the magnitude of genetic
      differentiation tended to increase with microhabitat dissimilarity under light
      conditions and water availability. Furthermore, most populations have been
      estimated to experience a recent decline in the effective population size,
      indicating a possibility of bottleneck effects on the pattern of genetic
      variation. These findings highlight a potential influence of the microhabitat
      conditions and demographic changes on the local-scale genetic differentiation
      among natural plant populations. 

PMID- 25387750
TI  - Differential drought tolerance in tree populations from contrasting elevations.
AB  - To predict the ecological consequences of climate change for a widely distributed
      tree species, it is essential to develop a deep understanding of the
      ecophysiological responses of populations from contrasting climates to varied
      soil water availabilities. In the present study, we focused on Pinus
      tabuliformis, one of the most economically and ecologically important tree
      species in China. In a greenhouse experiment, we exposed trees from high
      elevation (HP) and low-elevation (LP) populations to low (80 % of field capacity,
      FC), mild (60 % FC), moderate (40 % FC) and severe (20 % FC) water stresses. Leaf
      gas exchange, biomass production and allocation, as well as water-use efficiency,
      were measured during the experiment. Increasing soil water stress clearly
      decreased the relative growth rate (RGR), total dry mass (TDM), light-saturated
      photosynthetic rate (Asat), stomatal conductance (gs), total water use (TWU) and
      whole-plant water-use efficiency (WUEWP). In contrast, intrinsic water-use
      efficiency (WUEi) and carbon isotope composition (delta(13)C) both increased
      significantly with increasing soil water stress for both populations. Only in the
      LP did the root/shoot ratio (R/S ratio) significantly increase when the water
      stress increased. A strong positive correlation between Asat and gs coupled with
      a reduced intercellular CO2 concentration (Ci) probably suggested that stomatal
      limitations were the main cause of the decreased Asat. However, all the measured
      variables from the HP were affected less by drought compared with those of the
      LP, and most aspects of the HP were canalized against drought stress, which was
      reflected by the relatively higher RGR, TDM and WUEWP. Overall, the results
      suggest that the two populations responded differentially to drought stress with
      the HP showing higher drought tolerance than the LP, which was reflected by its
      faster seedling growth rate and more efficient water use under drought
      conditions. 

PMID- 25387751
TI  - Activated carbon decreases invasive plant growth by mediating plant-microbe
      interactions.
AB  - There is growing appreciation for the idea that plant-soil interactions (e.g.
      allelopathy and plant-microbe feedbacks) may explain the success of some non
      native plants. Where this is the case, native plant restoration may require
      management tools that change plant-soil interactions. Activated carbon (AC) is
      one such potential tool. Previous research has shown the potential for high
      concentrations of AC to restore native plant growth to areas dominated by non
      natives on a small scale (1 m * 1 m plots). Here we (i) test the efficacy of
      different AC concentrations at a larger scale (15 m * 15 m plots), (ii) measure
      microbial responses to AC treatment and (iii) use a greenhouse experiment to
      identify the primary mechanism, allelopathy versus microbial changes, through
      which AC impacts native and non-native plant growth. Three years after large
      scale applications, AC treatments decreased non-native plant cover and increased
      the ratio of native to non-native species cover, particularly at concentrations
      >400 g m(-2). Activated carbon similarly decreased non-native plant growth in the
      greenhouse. This effect, however, was only observed in live soils, suggesting
      that AC effects were microbially mediated and not caused by direct allelopathy.
      Bacterial community analysis of field soils indicated that AC increased the
      relative abundance of an unidentified bacterium and an Actinomycetales and
      decreased the relative abundance of a Flavobacterium, suggesting that these
      organisms may play a role in AC effects on plant growth. Results support the idea
      that manipulations of plant-microbe interactions may provide novel and effective
      ways of directing plant growth and community development (e.g. native plant
      restoration). 

PMID- 25387752
TI  - Salicornia as a crop plant in temperate regions: selection of genetically
      characterized ecotypes and optimization of their cultivation conditions.
AB  - Rising sea levels and salinization of groundwater due to global climate change
      result in fast-dwindling sources of freshwater. Therefore, it is important to
      find alternatives to grow food crops and vegetables. Halophytes are naturally
      evolved salt-tolerant plants that are adapted to grow in environments that
      inhibit the growth of most glycophytic crop plants substantially. Members of the
      Salicornioideae are promising candidates for saline agriculture due to their high
      tolerance to salinity. Our aim was to develop genetically characterized lines of
      Salicornia and Sarcocornia for further breeding and to determine optimal
      cultivation conditions. To obtain a large and diverse genetic pool, seeds were
      collected from different countries and ecological conditions. The external
      transcribed spacer (ETS) sequence of 62 Salicornia and Sarcocornia accessions was
      analysed: ETS sequence data showed a clear distinction between the two genera and
      between different Salicornia taxa. However, in some cases the ETS was not
      sufficiently variable to resolve morphologically distinct species. For the
      determination of optimal cultivation conditions, experiments on germination,
      seedling establishment and growth to a harvestable size were performed using
      different accessions of Salicornia spp. Experiments revealed that the percentage
      germination was greatest at lower salinities and with temperatures of 20/10 
      degrees C (day/night). Salicornia spp. produced more harvestable biomass in
      hydroponic culture than in sand culture, but the nutrient concentration requires
      optimization as hydroponically grown plants showed symptoms of stress. Salicornia
      ramosissima produced more harvestable biomass than Salicornia dolichostachya in
      artificial sea water containing 257 mM NaCl. Based on preliminary tests on ease
      of cultivation, gain in biomass, morphology and taste, S. dolichostachya was
      investigated in more detail, and the optimal salinity for seedling establishment
      was found to be 100 mM. Harvesting of S. dolichostachya twice in a growing season
      was successful, but the interval between the harvests needs to be optimized to
      maximize biomass production. 

PMID- 25387754
TI  - The mitochondrial fusion-related proteins Mfn2 and OPA1 are transcriptionally
      induced during differentiation of bone marrow progenitors to immature dendritic
      cells.
AB  - The shape and activity of mitochondria are tightly regulated by fusion and
      fission processes that are essential for maintaining normal cellular function.
      However, little is known about the involvement of mitochondrial dynamics in the
      development of the immune system. In this study, we demonstrate that
      mitochondrial dynamics play a role in the differentiation and migration of
      immature dendritic cells (imDCs). We show that mitochondrial elongation is
      induced during GM-CSF-stimulated differentiation of bone marrow progenitors to
      imDCs accompanied by upregulation of mitochondrial fusion proteins. These
      processes precede the changes in mitochondrial morphology and connectivity that
      occur during differentiation. Mfn2 and OPA1, but not Mfn1, are transcriptionally
      upregulated during differentiation; however, knockdown of Mfn2 and OPA1 does not
      induce any change in expression of CD11c, CDC80, or CD86. Notably, knockdown of
      Mfn2 or OPA1 by siRNA in imDCs significantly reduces CCR7 expression and CCL19
      mediated migration. These results suggest that the mitochondrial fusion-related
      proteins Mfn2 and OPA1 are upregulated during bone marrow progenitor
      differentiation and promote the migration of imDCs by regulating the expression
      of CCR7. 

PMID- 25387755
TI  - Pathogen associated molecular pattern (PAMP)-triggered immunity is compromised
      under C-limited growth.
AB  - In the interaction between plants and pathogens, carbon (C) resources provide
      energy and C skeletons to maintain, among many functions, the plant immune
      system. However, variations in C availability on pathogen associated molecular
      pattern (PAMP) triggered immunity (PTI) have not been systematically examined.
      Here, three types of starch mutants with enhanced susceptibility to Pseudomonas
      syringae pv. tomato DC3000 hrcC were examined for PTI. In a dark period-dependent
      manner, the mutants showed compromised induction of a PTI marker, and callose
      accumulation in response to the bacterial PAMP flagellin, flg22. In combination
      with weakened PTI responses in wild type by inhibition of the TCA cycle, the
      experiments determined the necessity of C-derived energy in establishing PTI.
      Global gene expression analyses identified flg22 responsive genes displaying C
      supply-dependent patterns. Nutrient recycling-related genes were regulated
      similarly by C-limitation and flg22, indicating re-arrangements of expression
      programs to redirect resources that establish or strengthen PTI. Ethylene and NAC
      transcription factors appear to play roles in these processes. Under C
      limitation, PTI appears compromised based on suppression of genes required for
      continued biosynthetic capacity and defenses through flg22. Our results provide a
      foundation for the intuitive perception of the interplay between plant nutrition
      status and pathogen defense. 

PMID- 25387756
TI  - Impact of maternal age on obstetric and neonatal outcome with emphasis on
      primiparous adolescents and older women: a Swedish Medical Birth Register Study.
AB  - OBJECTIVES: To evaluate the associations between maternal age and obstetric and
      neonatal outcomes in primiparous women with emphasis on teenagers and older
      women. DESIGN: A population-based cohort study. SETTING: The Swedish Medical
      Birth Register. PARTICIPANTS: Primiparous women with singleton births from 1992
      through 2010 (N=798,674) were divided into seven age groups: <17 years, 17-19
      years and an additional five 5-year classes. The reference group consisted of the
      women aged 25-29 years. PRIMARY OUTCOME: Obstetric and neonatal outcome. RESULTS:
      The teenager groups had significantly more vaginal births (adjusted OR (aOR) 2.04
      (1.79 to 2.32) and 1.95 (1.88 to 2.02) for age <17 years and 17-19 years,
      respectively); fewer caesarean sections (aOR 0.57 (0.48 to 0.67) and 0.55 (0.53
      to 0.58)), and instrumental vaginal births (aOR 0.43 (0.36 to 0.52) and 0.50
      (0.48 to 0.53)) compared with the reference group. The opposite was found among
      older women reaching a fourfold increased OR for caesarean section. The teenagers
      showed no increased risk of adverse neonatal outcome but presented an increased
      risk of prematurity <32 weeks (aOR 1.66 (1.10 to 2.51) and 1.20 (1.04 to 1.38)).
      Women with advancing age (>=30 years) revealed significantly increased risk of
      prematurity, perineal lacerations, preeclampsia, abruption, placenta previa,
      postpartum haemorrhage and unfavourable neonatal outcomes compared with the
      reference group. CONCLUSIONS: For clinicians counselling young women it is of
      importance to highlight the obstetrically positive consequences that fewer
      maternal complications and favourable neonatal outcomes are expected. The results
      imply that there is a need for individualising antenatal surveillance programmes
      and obstetric care based on age grouping in order to attempt to improve the
      outcomes in the age groups with less favourable obstetric and neonatal outcomes.
      Such changes in surveillance programmes and obstetric interventions need to be
      evaluated in further studies.

PMID- 25387757
TI  - High prevalence of hepatitis B virus infection among pregnant women attending
      antenatal care: a cross-sectional study in two hospitals in northern Uganda.
AB  - OBJECTIVE: To determine the prevalence of the hepatitis B viral (HBV) infection
      and hepatitis B e antigen (HBeAg) positivity among pregnant women attending
      antenatal clinics in two referral hospitals in northern Uganda. DESIGN: Cross
      sectional observational study. SETTING: Two tertiary hospitals in a postconflict
      region in a low-income country. PARTICIPANTS: Randomly selected 402 pregnant
      women attending routine antenatal care in two referral hospitals. Five women
      withdrew consent for personal reasons. Data were analysed for 397 participants.
      PRIMARY OUTCOME: Hepatitis B surface antigen (HBsAg) positivity. RESULTS: Of 397
      pregnant women aged 13-43 years, 96.2% were married or cohabiting. 47 (11.8%)
      tested positive for HBsAg; of these, 7 (14.9%) were HBeAg positive. The highest
      HBsAg positivity rate was seen in women aged 20 years or less (20%) compared with
      those aged above 20 years (8.7%), aOR=2.54 (95% CI 1.31 to 4.90). However, there
      was no statistically significant difference between women with positive HBsAg and
      those with negative tests results with respect to median values of liver enzymes,
      haemoglobin level, absolute neutrophil counts and white cell counts. HIV
      positivity, scarification and number of sexual partners were not predictive of
      HBV positivity. CONCLUSIONS: One in eight pregnant women attending antenatal care
      in the two study hospitals has evidence of hepatitis B infection. A significant
      number of these mothers are HBeAg positive and may be at increased risk of
      transmitting hepatitis B infection to their unborn babies. We suggest that all
      pregnant women attending antenatal care be tested for HBV infection; exposed
      babies need to receive HBV vaccines at birth.

PMID- 25387758
TI  - How context affects electronic health record-based test result follow-up: a mixed
      methods evaluation.
AB  - OBJECTIVES: Electronic health record (EHR)-based alerts can facilitate
      transmission of test results to healthcare providers, helping ensure timely and
      appropriate follow-up. However, failure to follow-up on abnormal test results
      (missed test results) persists in EHR-enabled healthcare settings. We aimed to
      identify contextual factors associated with facility-level variation in missed
      test results within the Veterans Affairs (VA) health system. DESIGN, SETTING AND
      PARTICIPANTS: Based on a previous survey, we categorised VA facilities according
      to primary care providers' (PCPs') perceptions of low (n=20) versus high (n=20)
      risk of missed test results. We interviewed facility representatives to collect
      data on several contextual factors derived from a sociotechnical conceptual model
      of safe and effective EHR use. We compared these factors between facilities
      categorised as low and high perceived risk, adjusting for structural
      characteristics. RESULTS: Facilities with low perceived risk were significantly
      more likely to use specific strategies to prevent alerts from being lost to
      follow-up (p=0.0114). Qualitative analysis identified three high-risk scenarios
      for missed test results: alerts on tests ordered by trainees, alerts 'handed off'
      to another covering clinician (surrogate clinician), and alerts on patients not
      assigned in the EHR to a PCP. Test result management policies and procedures to
      address these high-risk situations varied considerably across facilities.
      CONCLUSIONS: Our study identified several scenarios that pose a higher risk for
      missed test results in EHR-based healthcare systems. In addition to implementing
      provider-level strategies to prevent missed test results, healthcare
      organisations should consider implementing monitoring systems to track missed
      test results.

PMID- 25387759
TI  - Daytime napping, sleep duration and serum C reactive protein: a population-based
      cohort study.
AB  - OBJECTIVES: To explore whether daytime napping and sleep duration are linked to
      serum C reactive protein (CRP), a pro-inflammatory marker, in an older aged
      British population. DESIGN: Cross-sectional study. SETTING: European Prospective
      Investigation into Cancer and Nutrition (EPIC)-Norfolk study. PARTICIPANTS: A
      total of 5018 men and women aged 48-92 years reported their sleep habits and had
      serum CRP levels measured. OUTCOME AND MEASURES: CRP was measured (mg/L) during
      2006-2011 in fresh blood samples using high-sensitivity methods. Participants
      reported napping habits during 2002-2004, and reported sleep quantity during 2006
      2007. Multivariable linear regression models were used to examine the association
      between napping and log-transformed CRP, and geometric mean CRP levels were
      calculated. RESULTS: After adjustment for age and sex, those who reported napping
      had 10% higher CRP levels compared with those not napping. The association was
      attenuated but remained borderline significant (beta=0.05 (95% CI 0.00 to 0.10))
      after further adjustment for social class, education, marital status, body mass
      index, physical activity, smoking, alcohol intake, self-reported health, pre
      existing diseases, systolic blood pressure, hypnotic drug use, depression and in
      women-only hormone replacement therapy use. The geometric means (95% CI) of CRP
      levels were 2.38 (2.29 to 2.47) mg/L and 2.26 (2.21 to 2.32) mg/L for those who
      reported napping and no napping, respectively. A U-shaped association was
      observed between time spent in bed at night and CRP levels, and nighttime sleep
      duration was not associated with serum CRP levels. The association between
      napping and CRP was stronger for older participants, and among extremes of time
      spent in bed at night. CONCLUSIONS: Daytime napping was associated with increased
      CRP levels in an older aged British population. Further studies are needed to
      determine whether daytime napping is a cause for systemic inflammation, or if it
      is a symptom or consequence of underlying health problems.

PMID- 25387760
TI  - Retrospective case review of missed opportunities for primary prevention of
      stroke and TIA in primary care: protocol paper.
AB  - INTRODUCTION: Stroke is a major health problem and transient ischaemic attack
      (TIA) is an important risk factor for stroke. Primary prevention of stroke and
      TIA will have the greatest impact on reducing the burden of these conditions.
      Evidence-based guidelines for stroke/TIA prevention identify individuals eligible
      for preventative interventions in primary care. This study will investigate: (1)
      the proportion of strokes/TIAs with prior missed opportunities for prevention in
      primary care; (2) the influence of patient characteristics on missed prevention
      opportunities and (3) how the proportion of missed prevention opportunities has
      changed over time. METHODS AND ANALYSIS: A retrospective case review will
      identify first-ever stroke and patients with TIA between 2000 and 2013 using
      anonymised electronic medical records extracted from the health improvement
      network (THIN) database. Four categories of missed opportunities for stroke/TIA
      prevention will be sought: untreated high blood pressure in patients eligible for
      treatment (either blood pressure >=160/100 or >=140/90 mm Hg in patients at high
      cardiovascular disease (CVD) risk); patients with atrial fibrillation with high
      stroke risk and no anticoagulant therapy; no lipid modifying drug therapy
      prescribed in patients at high CVD risk or with familial hypercholesterolaemia.
      The proportion of patients with each missed opportunity and multiple missed
      opportunities will be calculated. Mixed effect logistic regression will model the
      relationship between demographic and patient characteristics and missed
      opportunities for care; practice will be included as a random effect. ETHICS AND
      DISSEMINATION: THIN data collection was approved by the NHS South East Multi
      centre Research Ethics Committee (MREC) in 2003. This study was approved by the
      independent scientific review committee in May 2013. Dissemination of findings
      has the potential to change practice, improve the quality of care provided to
      patients and ultimately reduce the incidence of strokes and TIAs. Findings will
      be published in a peer-reviewed journal and disseminated at national and
      international conferences.

PMID- 25387761
TI  - Effect of hemodialysis on pharmacokinetics of ezogabine/retigabine and its N
      acetyl metabolite in patients with end stage renal disease.
AB  - Ezogabine (EZG)/retigabine (RTG) and its metabolites are mainly eliminated
      renally. This Phase I study assessed the effect of hemodialysis on the
      pharmacokinetics of EZG/RTG and its N-acetyl metabolite (NAMR) in patients with
      end-stage renal disease; tolerability of EZG/RTG was a secondary endpoint.
      Patients (N=8) received EZG/RTG 100 mg orally 4 hours before (Period 1) or
      following (Period 2) dialysis. Blood (both periods) and dialysate (Period 1)
      samples were taken up to 68 hours post dose. Tolerability was assessed throughout
      both periods. The area under the concentration- time curve (0-68 hours) for
      EZG/RTG was 33% lower (geometric mean ratio [90% confidence interval]: 0.67
      [0.61, 0.73]) on dialysis versus off dialysis and 43% lower for NAMR (0.57 [0.53,
      0.62]). Median (range) reductions in plasma concentrations from dialysis start to
      end were 52% (17-59%) for EZG/RTG and 51% (27-72%) for NAMR. EZG/RTG 100 mg was
      generally tolerated.

PMID- 25387762
TI  - Trust in decision-making authorities dictates the form of the interactive
      relationship between outcome fairness and procedural fairness.
AB  - Reactions to decisions are shaped by both outcome and procedural fairness.
      Moreover, outcome and procedural fairness interact to influence beliefs and
      behaviors. However, different types of "process/outcome" interaction effects have
      emerged. Many studies have shown that people react particularly negatively when
      they receive unfair or unfavorable outcomes accompanied by unfair procedures (the
      "low-low" interactive pattern). However, others find that people react especially
      positively when they receive fair or favorable outcomes accompanied by fair
      procedures (the "high-high" interactive pattern). We propose that trust in
      decision-making authorities dictates the form of the process/outcome interaction.
      Across three studies, when trust was high, the "low-low" interactive pattern
      emerged. When trust was low, the "high-high" interactive pattern emerged. The
      findings suggest that when people's experience of outcome and procedural fairness
      diverged from how they expected to be treated, they reacted in the direction of
      their experiences; otherwise, their reactions were consistent with their
      expectations. 

PMID- 25387763
TI  - An update on ABO-incompatible kidney transplantation.
AB  - ABO-incompatible kidney transplantation is nowadays a well-established procedure
      to expand living donor transplantation to blood group incompatible
      donor/recipient constellations. In the last two decades, transplantation
      protocols evolved to more specific isohaemagglutinin elimination techniques and
      established competent antirejection protection protocols without the need of
      splenectomy. ABOi kidney transplantation associated accommodation despite
      isohaemagglutinin reappearance, C4d positivity of peritubular capillaries as well
      as the increased incidence of bleeding complications is currently under intense
      investigation. However, most recent data show excellent graft survival rates
      equivalent to ABO-compatible kidney transplantation outcome. 

PMID- 25387764
TI  - Predicting functional communication ability in children with cerebral palsy at
      school entry.
AB  - AIM: To explore the value of demographic, environmental, and early clinical
      characteristics in predicting functional communication in children with cerebral
      palsy (CP) at school entry. METHOD: Data are from an Australian prospective
      longitudinal study of children with CP. Children assessed at 18 to 24 and 48 to
      60 months corrected age were included in the study. Functional communication was
      classified at 48 to 60 months using the Communication Function Classification
      System (CFCS). Predictive variables included communication skills at 18 to 24
      months, evaluated using the Communication and Symbolic Behavioural Scales
      Developmental Profile (CSBS-DP) Infant-Toddler Checklist. Early Gross Motor
      Function Classification System (GMFCS), Manual Ability Classification System, and
      motor type and distribution were evaluated by two physiotherapists. Demographic
      and comorbid variables were obtained through parent interview with a
      paediatrician or rehabilitation specialist. RESULTS: A total of 114 children (76
      males, 38 females) were included in the study. At 18 to 24 months the mean CSBS
      DP was 84.9 (SD 19.0). The CFCS distribution at 48 to 60 months was I=36(32%),
      II=25(22%), III=20(18%), IV=19(17%), and V=14(12%). In multivariable regression
      analysis, only CSBS-DP (p<0.01) and GMFCS (p<0.01) at 18 to 24 months were
      predictors of functional communication at school entry. INTERPRETATION: Body
      structure and function and not environmental factors impact functional
      communication at school entry in children with CP. This provides valuable
      guidance for early screening, parent education, and future planning of
      intervention programs to improve functional communication.

PMID- 25387765
TI  - Reclassification of mammary carcinomas with neuroendocrine features in accordance
      with neuroendocrine morphologies in the revised World Health Organization
      classification.

PMID- 25387767
TI  - Are computers effective lie detectors? A meta-analysis of linguistic cues to
      deception.
AB  - This meta-analysis investigates linguistic cues to deception and whether these
      cues can be detected with computer programs. We integrated operational
      definitions for 79 cues from 44 studies where software had been used to identify
      linguistic deception cues. These cues were allocated to six research questions.
      As expected, the meta-analyses demonstrated that, relative to truth-tellers,
      liars experienced greater cognitive load, expressed more negative emotions,
      distanced themselves more from events, expressed fewer sensory-perceptual words,
      and referred less often to cognitive processes. However, liars were not more
      uncertain than truth-tellers. These effects were moderated by event type,
      involvement, emotional valence, intensity of interaction, motivation, and other
      moderators. Although the overall effect size was small, theory-driven predictions
      for certain cues received support. These findings not only further our knowledge
      about the usefulness of linguistic cues to detect deception with computers in
      applied settings but also elucidate the relationship between language and
      deception. 

PMID- 25387766
TI  - NOTCH decoys that selectively block DLL/NOTCH or JAG/NOTCH disrupt angiogenesis
      by unique mechanisms to inhibit tumor growth.
AB  - A proangiogenic role for Jagged (JAG)-dependent activation of NOTCH signaling in
      the endothelium has yet to be described. Using proteins that encoded different
      NOTCH1 EGF-like repeats, we identified unique regions of Delta-like ligand (DLL)
      class and JAG-class ligand-receptor interactions, and developed NOTCH decoys that
      function as ligand-specific NOTCH inhibitors. N110-24 decoy blocked JAG1/JAG2
      mediated NOTCH1 signaling, angiogenic sprouting in vitro, and retinal
      angiogenesis, demonstrating that JAG-dependent NOTCH signal activation promotes
      angiogenesis. In tumors, N110-24 decoy reduced angiogenic sprouting, vessel
      perfusion, pericyte coverage, and tumor growth. JAG-NOTCH signaling uniquely
      inhibited expression of antiangiogenic soluble (s) VEGFR1/sFLT1. N11-13 decoy
      interfered with DLL1-DLL4-mediated NOTCH1 signaling and caused endothelial
      hypersprouting in vitro, in retinal angiogenesis, and in tumors. Thus, blockade
      of JAG- or DLL-mediated NOTCH signaling inhibits angiogenesis by distinct
      mechanisms. JAG-NOTCH signaling positively regulates angiogenesis by suppressing
      sVEGFR1-sFLT1 and promoting mural-endothelial cell interactions. Blockade of JAG
      class ligands represents a novel, viable therapeutic approach to block tumor
      angiogenesis and growth. SIGNIFICANCE: This is the first report identifying
      unique regions of the NOTCH1 extracellular domain that interact with JAG-class
      and DLL-class ligands. Using this knowledge, we developed therapeutic agents that
      block JAG-dependent NOTCH signaling and demonstrate for the first time that JAG
      blockade inhibits experimental tumor growth by targeting tumor angiogenesis.

PMID- 25387768
TI  - Vitamin D, virus etiology, and atopy in first-time wheezing children in Finland.

PMID- 25387769
TI  - Structure-dynamic determinants governing a mode of regulatory response and
      propagation of allosteric signal in splice variants of Na+/Ca2+ exchange (NCX)
      proteins.
AB  - The Ca(2+)-dependent allosteric regulation of Na(+)/Ca(2+) exchanger (NCX)
      proteins represents Ca(2+) interaction with the cytosolic domains, CBD1 (calcium
      binding domain 1) and CBD2, which is associated either with activation,
      inhibition or no response to regulatory Ca(2+) in a given splice variant. CBD1
      contains a high affinity Ca(2+)-sensor (which is highly conserved among splice
      variants), whereas primary information upon Ca(2+) binding to CBD1 is modified by
      alternative splicing of CBD2, yielding the diverse regulatory responses to
      Ca(2+). To resolve the structure-dynamic determinants of splicing-dependent
      regulation, we tested two-domain tandem (CBD12) constructs possessing either
      positive, negative or no response to Ca(2+) using hydrogen-deuterium exchange MS
      (HDX-MS), SAXS, equilibrium 45Ca(2+) binding and stopped-flow kinetics. Taken
      together with previously resolved crystallographic structures of CBD12, the data
      revealed that Ca(2+) binding to CBD1 rigidifies the main-chain flexibility of
      CBD2 (but not of CBD1), whereas CBD2 stabilizes the apo-CBD1. Strikingly, the
      extent and strength of Ca(2+)-dependent rigidification of CBD2 is splice-variant
      dependent, where the main-chain rigidification spans from the Ca(2+)-binding
      sites of CBD1, through a helix of CBD2 (positioned at the domains' interface) up
      to the tip of CBD2 [>50 A (1 A = 0.1 nm)] or alternatively, it stops at the CBD2
      helix in the splice variant exhibiting an inhibitory response to regulatory
      Ca(2+). These results provide a structure-dynamic basis by which alternative
      splicing diversifies the regulatory responses to Ca(2+) as well as controls the
      extent and strength of allosteric signal propagation over long distance.

PMID- 25387770
TI  - Magnetic resonance enterocolonography in detecting erosion and redness in
      intestinal mucosa of patients with Crohn's disease.
AB  - BACKGROUND AND AIM: In Crohn's disease (CD), assessment of disease activity and
      extension is important for clinical management. Endoscopy is the most reliable
      tool for evaluating disease activity in these patients and it distinguishes
      between lesions based on ulcer, erosion, and redness. Magnetic resonance imaging
      (MRI) is less invasive than endoscopy; however, the sensitivity of MRI in
      detecting lesions is believed to be lower, and whether MRI can detect milder
      lesions has not been studied. The aim of this study was to compare the detection
      ability of magnetic resonance enterocolonography (MREC) with ileocolonic
      endoscopy in patients with CD. METHODS: A total of 27 patients with CD underwent
      both MREC and ileocolonoscopy. There were 55 lesions (18 ileum and 37 colon)
      endoscopically detected, and the findings of MREC were compared with each
      ileocolonoscopic finding to determine sensitivity and specificity. RESULTS: For a
      positive lesion defined as having at least one of the following: wall thickness,
      edema, diffusion-weighted imaging (DWI) high intensity and relative contrast
      enhancement (RCE) on MREC, the sensitivities were 100% for ulcer, 84.6% for
      erosion, and 52.9% for redness, suggesting an ability to detect milder lesions
      such as erosion or redness. Moreover, RCE values were well correlated with the
      severity of endoscopically identified active lesions. CONCLUSION: MREC findings
      may be useful not only for evaluation of ulcers, but also for detection of
      endoscopically identified milder lesions in CD, suggesting a clinical usefulness
      of MREC for disease detection and monitoring.

PMID- 25387771
TI  - The planar cell polarity protein Vangl2 bidirectionally regulates dendritic
      branching in cultured hippocampal neurons.
AB  - BACKGROUND: Van Gogh-like (Vangl) 2 is a planar cell polarity (PCP) protein that
      regulates the induction of polarized cellular and tissue morphology during animal
      development. In the nervous system, the core PCP signaling proteins have been
      identified to regulate neuronal maturation. In axonal growth cones, the
      antagonistic interaction of PCP components makes the tips of filopodia sensitive
      to guidance cues. However, the molecular mechanism by which the PCP signaling
      regulates spine and dendritic development remains obscure. FINDINGS: Here we
      explored the finding that a loss of function of Vangl2 results in a significant
      reduction in spine density and complexity of dendritic branching. In spite of a
      previous report, in which the Vangl2 C-terminal TSV motif was shown to be
      required for the interaction with PSD-95 and the C-terminal intracellular domain
      was shown to associate with N-cadherin, overexpression of deletion mutants
      (Vangl2-?TSV and Vangl2-?C) had little effect on spine density. However, when an
      N-terminal region deletion mutant was overexpressed, spine density was slightly
      down-regulated. Intriguingly, the deletion mutants had a more potent effect on
      dendritic branching, such that the deletion of the N-terminal region reduced
      dendritic branching, whereas deletion of the C-terminal region increased it.
      CONCLUSIONS: Based on these results, Vangl2, a core PCP signaling pathway
      component, appears to have a functional role in neural complex formation.
      Especially in the case of dendritic branching, Vangl2 serves as a molecular hub
      to regulate neural morphology in opposite directions.

PMID- 25387773
TI  - Diets, diatribes, and a dearth of data.

PMID- 25387772
TI  - Functional disability and cognitive impairment after hospitalization for
      myocardial infarction and stroke.
AB  - BACKGROUND: We assessed the acute and long-term effect of myocardial infarction
      (MI) and stroke on postevent functional disability and cognition while
      controlling for survivors' changes in functioning over the years before the
      event. METHODS AND RESULTS: Among participants in the nationally representative
      Health and Retirement Study with linked Medicare data (1998-2010), we determined
      within-person changes in functional limitations (basic and instrumental
      activities of daily living) and cognitive impairment after hospitalization for
      stroke (n=432) and MI (n=450), controlling for premorbid functioning using fixed
      effects regression. In persons without baseline impairments, an acute MI yielded
      a mean acute increase of 0.41 functional limitations (95% confidence interval
      [CI], 0.18-0.63) with a linear increase of 0.14 limitations/year in the following
      decade. These increases were 0.65 limitations (95% CI, 0.07-1.23) and 0.27
      limitations/year afterward for those with mild-to-moderate impairment at
      baseline. Stroke resulted in an acute increase of 2.07 (95% CI, 1.51-2.63)
      limitations because of the acute event and an increase of 0.15 limitations/year
      afterward for those unimpaired at baseline. There were 2.65 new limitations (95%
      CI, 1.86-3.44) and 0.19/year afterward for those with baseline mild-to-moderate
      impairment. Stroke hospitalization was associated with greater odds of moderate
      to-severe cognitive impairment (odds ratio, 3.86; 95% CI, 2.10-7.11) at the time
      of the event, after adjustment for premorbid cognition but MI hospitalization was
      not. CONCLUSIONS: In this population-based cohort, most MI and stroke
      hospitalizations were associated with significant increases in functional
      disability at the time of the event and in the decade afterward. Survivors of MI
      and stroke warrant screening for functional disability over the long-term.

PMID- 25387774
TI  - Dawning of a new era: understanding the functional outcomes of cardiovascular
      disease.

PMID- 25387775
TI  - Managing the information boundary of an organization: key aspect of translating
      research into practice.

PMID- 25387776
TI  - Adverse clinical event peer review must evolve to be relevant to quality
      improvement.

PMID- 25387777
TI  - Payments for acute myocardial infarction episodes-of-care initiated at hospitals
      with and without interventional capabilities.
AB  - BACKGROUND: It is unknown whether hospitals with percutaneous coronary
      intervention (PCI) capability provide costlier care than hospitals without PCI
      capability for patients with acute myocardial infarction. The growing number of
      PCI hospitals and higher rate of PCI use may result in higher costs for episodes
      of-care initiated at PCI hospitals. However, higher rates of transfers and
      postacute care procedures may result in higher costs for episodes-of-care
      initiated at non-PCI hospitals. METHODS AND RESULTS: We identified all 2008 acute
      myocardial infarction admissions among Medicare fee-for-service beneficiaries by
      principal discharge diagnosis and classified hospitals as PCI- or non-PCI-capable
      on the basis of hospitals' 2007 PCI performance. We added all payments from
      admission through 30 days postadmission, including payments to hospitals other
      than the admitting hospital. We calculated and compared risk-standardized payment
      for PCI and non-PCI hospitals using 2-level hierarchical generalized linear
      models, adjusting for patient demographics and clinical characteristics. PCI
      hospitals had a higher mean 30-day risk-standardized payment than non-PCI
      hospitals (PCI, $20 340; non-PCI, $19 713; P<0.001). Patients presenting to PCI
      hospitals had higher PCI rates (39.2% versus 13.2%; P<0.001) and higher coronary
      artery bypass graft rates (9.5% versus 4.4%; P<0.001) during index admissions,
      lower transfer rates (2.2% versus 25.4%; P<0.001), and lower revascularization
      rates within 30 days (0.15% versus 0.27%; P<0.0001) than those presenting to non
      PCI hospitals. CONCLUSIONS: Despite higher PCI and coronary artery bypass graft
      rates for Medicare patients initially presenting to PCI hospitals, PCI hospitals
      were only $627 costlier than non-PCI hospitals for the treatment of patients with
      acute myocardial infarction in 2008.

PMID- 25387778
TI  - Long-term effects of 4 popular diets on weight loss and cardiovascular risk
      factors: a systematic review of randomized controlled trials.
AB  - BACKGROUND: We conducted a systematic review to examine the efficacy of the
      Atkins, South Beach, Weight Watchers (WW), and Zone diets, with a particular
      focus on sustained weight loss at >=12 months. METHODS AND RESULTS: We
      systematically searched MEDLINE, EMBASE, and the Cochrane Library of Clinical
      Trials to identify randomized controlled trials (RCTs) published in English with
      follow-up >=4 weeks that examined the effects of these 4 popular diets on weight
      loss and cardiovascular risk factors. We identified 12 RCTs (n=2559) with follow
      up >=12 months: 10 versus usual care (5 Atkins, 4 WW, and 1 South Beach) and 2
      head-to-head (1 of Atkins, WW, and Zone, and 1 of Atkins, Zone, and control). At
      12 months, the 10 RCTs comparing popular diets to usual care revealed that only
      WW was consistently more efficacious at reducing weight (range of mean changes: 
      3.5 to -6.0 kg versus -0.8 to -5.4 kg; P<0.05 for 3/4 RCTs). However, the 2 head
      to-head RCTs suggest that Atkins (range: -2.1 to -4.7 kg), WW (-3.0 kg), Zone (
      1.6 to -3.2 kg), and control (-2.2 kg) all achieved modest long-term weight loss.
      Twenty-four-month data suggest that weight lost with Atkins or WW is partially
      regained over time. CONCLUSIONS: Head-to-head RCTs, providing the most robust
      evidence available, demonstrated that Atkins, WW, and Zone achieved modest and
      similar long-term weight loss. Despite millions of dollars spent on popular
      commercial diets, data are conflicting and insufficient to identify one popular
      diet as being more beneficial than the others.

PMID- 25387779
TI  - Certain uncertainty: life after stroke from the patient's perspective.

PMID- 25387780
TI  - Health-related quality of life in patients with atrial fibrillation treated with
      rhythm control versus rate control: insights from a prospective international
      registry (Registry on Cardiac Rhythm Disorders Assessing the Control of Atrial
      Fibrillation: RECORD-AF).
AB  - BACKGROUND: Improving health-related quality of life (HRQoL) is an important
      treatment goal in the management of patients with atrial fibrillation (AF).
      Uncertainty exists as to whether patients' HRQoL differ when treated with medical
      rhythm control or rate control. We compared HRQoL between patients treated with
      rhythm control or rate control in a large observational registry of patients with
      recent-onset AF. METHODS AND RESULTS: In the Registry on Cardiac Rhythm Disorders
      Assessing the Control of Atrial Fibrillation (RECORD-AF), 2439 patients with
      recent onset (<1 year) AF completed an AF-specific HRQoL questionnaire, the
      University of Toronto Atrial Fibrillation Severity Scale. HRQoL was assessed by
      the AF symptom severity score (0-35, with higher scores reflecting more severe AF
      related symptoms) at baseline and 1 year. The minimal clinically important
      difference was defined as a change of >=3 points. The primary analysis was based
      on a propensity score-adjusted longitudinal regression analysis which compared
      the change in AF symptom severity scores between the 2 groups. Over an average
      follow-up of 1 year, the AF symptom severity scores improved in both groups
      (rhythm control: -2.82 point [95% confidence interval, -3.22 to -2.41]; rate
      control: -2.11 point [95% confidence interval, -2.54 to -1.67]; P<0.01 for both
      groups). The magnitude of improvement was higher in the rhythm control group than
      the rate control group (unadjusted difference: -0.75 point; 95% confidence
      interval, -1.31 to -0.19; P=0.01; propensity score-adjusted difference: -0.71
      point; 95% confidence interval, -1.31 to -0.11; P=0.02). CONCLUSIONS: In this
      observational cohort of recent-onset AF patients, treatment with medical rhythm-
      or rate control over 1 year was associated with an improvement in HRQoL. The
      magnitude of HRQoL improvement was minimally higher in patients treated with
      rhythm control than rate control. However, the overall degree of improvement was
      not large, and its clinical significance was uncertain.

PMID- 25387781
TI  - Clinical commentary on "Certain uncertainty: life after stroke from the patient's
      perspective".

PMID- 25387782
TI  - Patients' preferences in anticoagulant therapy: discrete choice experiment.
AB  - BACKGROUND: With proliferating treatment options for anticoagulant therapy,
      physicians and patients must choose among them based on their benefits and risks.
      Using a Discrete Choice Experiment, we elicited patients' relative preferences
      for specific benefits and risks of anticoagulant therapy. METHODS AND RESULTS: We
      selected a sample of US patients with cardiovascular disease from an online panel
      and elicited their preferences for benefits and risks of anticoagulant therapy:
      nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, minor
      bleeding, major bleeding, bleeding death, and need for monitoring. These
      attributes were used to design scenarios describing hypothetical treatments that
      were labeled as new drug, old drug, or no drug. Latent class analysis was used to
      identify groups of patients with similar preferences. A total of 341 patients
      completed all Discrete Choice Experiment questions. On average, patients valued a
      1% increased risk of a fatal bleeding event the same as a 2% increase in nonfatal
      myocardial infarction, a 3% increase in nonfatal stroke, a 3% increase in
      cardiovascular death, a 6% increase in major bleeding, and a 16% increase in
      minor bleeding. The odds of choosing no drug or old drug versus new drug were
      0.72 (95% confidence interval, 0.61-0.84) and 0.86 (95% confidence interval, 0.81
      0.93), respectively. Previous stroke or myocardial infarction was associated with
      membership in the class with larger negative preferences for these outcomes.
      CONCLUSIONS: Patients' preferences for various outcomes of anticoagulant therapy
      vary and depend on their previous experiences with myocardial infarction or
      stroke. Incorporating these preferences into benefit risk calculation and
      treatment decisions can enhance patient-centered care.

PMID- 25387783
TI  - Hospital-level variation in angina and mortality at 1 year after myocardial
      infarction: insights from the Translational Research Investigating Underlying
      Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH)
      Registry.
AB  - BACKGROUND: Despite calls to expand measurement of acute myocardial infarction
      (AMI) outcomes to include symptom burden, little has been done to describe
      hospital-level variation in this patient-centered outcome, or its association
      with mortality. Understanding the relationship between symptoms and longer-term
      mortality could inform the importance of these outcomes for monitoring quality of
      care. METHODS AND RESULTS: Among 4316 patients with AMI treated at 24 hospitals
      participating in the Translational Research Investigating Underlying Disparities
      in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) study, we
      assessed risk-standardized 1-year symptom burden as measured by the Seattle
      Angina Questionnaire Angina Frequency Score and mortality attributed to the
      hospital that provided AMI care. Median odds ratios were used to assess outcome
      variation and reflect the relative odds of an outcome for 2 patients with
      identical covariates at different, randomly selected, hospitals. We then
      evaluated the correlation between hospital-level mortality and angina. Finally,
      we determined the extent to which variation in mortality and angina was explained
      by achievement of AMI performance measures. We observed hospital variation in
      risk-adjusted 1-year mortality (range, 4.9%-8.6%; median odds ratio, 1.30;
      P=0.01) and angina (range, 17.7%-29.4%; median odds ratio, 1.34; P<0.001). At the
      hospital level, mortality and angina at 1 year were weakly correlated (r=0.40;
      95% confidence interval, 0.00-0.68; P=0.05). Accounting for the quality of AMI
      care did not attenuate variation in risk-adjusted 1-year mortality or angina.
      CONCLUSIONS: Symptom burden and mortality vary at the hospital level after AMI
      and are only weakly correlated. These findings suggest that symptom burden should
      be considered a separate quality domain that is not well captured by current
      quality metrics.

PMID- 25387785
TI  - BDNF serum levels and promoter methylation of BDNF exon I, IV and VI in depressed
      patients receiving electroconvulsive therapy.
AB  - We examined potential changes in brain-derived neurotrophic factor (BDNF) serum
      levels and promoter methylation of the BDNF gene in 11 patients with treatment
      resistant major depressive disorder during a series of electroconvulsive therapy
      (ECT). Blood samples were taken before, 1 and 24 h after ECT treatment sessions
      1, 4, 7 and 10. Patients remitting under ECT had significantly lower mean
      promoter methylation rates, especially concerning the exon I promoter, compared
      to non-remitters (both p < 0.002). These findings may point to a depression
      subtype in which ECT is particularly beneficial.

PMID- 25387786
TI  - Gender and age differences in parent-child emotion talk.
AB  - This study examined gender differences in emotion word use during mother-child
      and father-child conversations. Sixty-five Spanish mothers and fathers and their
      4- (M = 53.50, SD = 3.54) and 6-year-old (M = 77.07, SD = 3.94) children
      participated in this study. Emotion talk was examined during a play-related
      storytelling task and a reminiscence task (conversation about past experiences).
      Mothers mentioned a higher proportion of emotion words than did fathers. During
      the play-related storytelling task, mothers of 4-year-old daughters mentioned a
      higher proportion of emotion words than did mothers of 4-year-old sons, whereas
      fathers of 4-year-old daughters directed a higher proportion of emotion words
      than did fathers of 4-year-old sons during the reminiscence task. No gender
      differences were found with parents of 6-year-old children. During the
      reminiscence task daughters mentioned more emotion words with their fathers than
      with their mothers. Finally, mothers' use of emotion talk was related to whether
      children used emotion talk in both tasks. Fathers' use of emotion talk was only
      related to children's emotion talk during the reminiscence task. 

PMID- 25387784
TI  - Invited review: overview of new traits and phenotyping strategies in dairy cattle
      with a focus on functional traits.
AB  - For several decades, breeding goals in dairy cattle focussed on increased milk
      production. However, many functional traits have negative genetic correlations
      with milk yield, and reductions in genetic merit for health and fitness have been
      observed. Herd management has been challenged to compensate for these effects and
      to balance fertility, udder health and metabolic diseases against increased
      production to maximize profit without compromising welfare. Functional traits,
      such as direct information on cow health, have also become more important because
      of growing concern about animal well-being and consumer demands for healthy and
      natural products. There are major concerns about the impact of drugs used in
      veterinary medicine on the spread of antibiotic-resistant strains of bacteria
      that can negatively impact human health. Sustainability and efficiency are also
      increasingly important because of the growing competition for high-quality, plant
      based sources of energy and protein. Disruptions to global environments because
      of climate change may encourage yet more emphasis on these traits. To be
      successful, it is vital that there be a balance between the effort required for
      data recording and subsequent benefits. The motivation of farmers and other
      stakeholders involved in documentation and recording is essential to ensure good
      data quality. To keep labour costs reasonable, existing data sources should be
      used as much as possible. Examples include the use of milk composition data to
      provide additional information about the metabolic status or energy balance of
      the animals. Recent advances in the use of mid-infrared spectroscopy to measure
      milk have shown considerable promise, and may provide cost-effective alternative
      phenotypes for difficult or expensive-to-measure traits, such as feed efficiency.
      There are other valuable data sources in countries that have compulsory
      documentation of veterinary treatments and drug use. Additional sources of data
      outside of the farm include, for example, slaughter houses (meat composition and
      quality) and veterinary labs (specific pathogens, viral loads). At the farm
      level, many data are available from automated and semi-automated milking and
      management systems. Electronic devices measuring physiological status or activity
      parameters can be used to predict events such as oestrus, and also behavioural
      traits. Challenges concerning the predictive biology of indicator traits or
      standardization need to be solved. To develop effective selection programmes for
      new traits, the development of large databases is necessary so that high
      reliability breeding values can be estimated. For expensive-to-record traits,
      extensive phenotyping in combination with genotyping of females is a possibility.

PMID- 25387787
TI  - Author's response: re 'mobile phone use and brain tumours in the CERENAT case
      control study'.

PMID- 25387788
TI  - Re: mobile phone use and brain tumours in the CERENAT case--control study.

PMID- 25387789
TI  - Editorial: Chemoinformatics in metabolomics, modeling chemical reactivity and
      ADMET processes part 1.

PMID- 25387790
TI  - An exploration of parents' perceptions and beliefs about changes following
      participation in a family skill training program: a qualitative study in a
      developing country.
AB  - Family skill training programs have been recognized as effective strategies for
      preventing substance use. However, they have been evaluated mainly in high-income
      countries. Families in developing countries also face difficulties; therefore, it
      is important to explore the fit of existing programs in this context. The present
      study explores parents' perceptions and beliefs about changes following
      participation in the Strengthening Families Program 10-14, which was implemented
      in Panama by the United Nations Office on Drugs and Crime. Thirty parents who had
      taken part in the program between 2010 and 2011 were interviewed. Thematic
      analysis was conducted taking a participant-driven inductive stand. An
      exploration of parents' narratives suggested that, after the program, they
      observed changes in themselves as parents, in their children, in the interaction
      between the two of them, and in their functioning as a couple. Perceived changes
      centered on communication, limits, obedience, relationship roles, emotional
      regulation, and social development. For example, parents reported being able to
      control their emotions in a healthier manner, reducing the use of shouting and
      setting limits in a more effective way. All these factors have been recognized in
      previous research as strategies for preventing substance use. It is important to
      assess participants' perceptions of programs brought from elsewhere before
      dissemination efforts can take place. Parents interviewed for this study appeared
      to hold positive views about this program. This methodology is discussed as a
      means of evaluating evidence-based interventions in different cultural settings. 

PMID- 25387795
TI  - A rare tetranuclear thorium(IV) MU4 -oxo cluster and dinuclear thorium(IV)
      complex assembled by carbon-oxygen bond activation of 1,2-dimethoxyethane (DME).
AB  - The synthesis and X-ray crystal structure of two new multinuclear thorium
      complexes are reported. The tetranuclear MU4 -oxo cluster complex Th4 (MU4 -O)(MU
      Cl)2 I6 [kappa(2) (O,O')-MU-O(CH2 )2 OCH3 ]6 and the dinuclear complex Th2 I5
      [kappa(2) (O,O')-MU-O(CH2 )2 OCH3 ]3 (DME) (DME=dimethoxyethane) are formed by
      C?O bond activation of 1,2-dimethoxyethane (DME) mediated by thorium iodide
      complexes. 

PMID- 25387791
TI  - PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent
      manner.
AB  - This study was aimed to determine the role and regulation of progranulin (PGRN)
      in the pathogenesis of inflammatory bowel diseases (IBD). Dextran sulfate sodium
      (DSS)-, picrylsulfonic acid (TNBS)-induced, bone marrow chimera and
      CD4+CD45Rb(hi) T cell transfer colitis model were established and analyzed in
      wild-type and several genetically-modified mice, including PGRN, IL-10 and TNFR2
      deficient mice. Elevated levels of PGRN were found in colitis samples from human
      IBD patients and mouse colitis models in comparison to the corresponding
      controls. PGRN-deficient mice became highly susceptible to DSS- and TNBS-induced
      colitis, whereas recombinant PGRN ameliorated the pathology and reduced the
      histological score in both DSS and TNBS colitis models. In addition,
      hematopoietic-derived PGRN was critical for protection against DSS-induced
      colitis, and lack of PGRN signaling in CD4+ T cells also exacerbated experimental
      colitis. PGRN-mediated protective effect in colitis was compromised in the
      absence of IL-10 signaling. In addition, PGRN's effect was also largely lost in
      the TNFR2-deficient colitis model. Collectively, these findings not only provide
      the new insight into PGRN's anti-inflammatory action in vivo, but may also
      present PGRN and its derivatives as novel biological agent for treating IBD.

PMID- 25387792
TI  - Asthma incidence, remission, relapse and persistence: a population-based study in
      southern Taiwan.
AB  - BACKGROUND: In western countries, late-onset asthmatics are more severe than
      early-onset asthmatics in clinic-based studies. However, whether asthma
      occurrence rates were higher in late ages than in younger ages was inconclusive.
      This information is essentially lacking in Asian population. METHODS: The
      participants were schoolchildren's parents recruited from 94 elementary and
      middle schools in 2004. A cross-sectional self-administered questionnaire was
      sent through the children to their parents to survey their respiratory health. We
      investigated typical asthma symptoms occurring at different ages and subsequent
      remission or relapse after the first asthma event. Person-years of the
      participants from birth to the time of survey were used as the denominator.
      RESULTS: Among the 25,377 participants consisting of 949,807 total person-years,
      860 reported ever having asthma. Highest incidences occurred at ages 0-12 and 36
      40 years. The incidence of asthma was higher in males before puberty, and higher
      in females after puberty, with overall incidences 1.00 and 0.77 per 1000 person
      years for females and males, respectively. Participants with late-onset asthma
      (onset age >12 years) comprised a large portion of adult current asthmatics. More
      than 52% of persistence or relapse was observed in early-onset asthma (onset age
      <=12 years). The younger birth cohort had a more prominent later peak of asthma
      incidence than the older one. CONCLUSIONS: In Asian population, asthma occurrence
      showed a U-shape age distribution with a prominent second peak in the thirties. A
      high proportion of early-onset asthma relapsed and most of late-onset asthma
      persisted or relapsed in adulthood.

PMID- 25387796
TI  - Activation of BV2 microglia by lipopolysaccharide triggers an inflammatory
      reaction in PC12 cell apoptosis through a toll-like receptor 4-dependent pathway.
AB  - Microglia play an important role in neuronal protection and damage. However, the
      molecular and cellular relationship between microglia and neurons is unclear. We
      carried out a prospective study to detect that activation of BV2 microglia
      induced PC12 cell apoptosis in vitro through the TLR4/adapter protein myeloid
      differentiation factor 88 (MyD88)/nuclear factor-kappaB (NF-kappaB) signaling
      pathway. BV2 microglia were treated with different concentrations of LPS for 24
      h. Western blot was utilized to detect the expression of TLR4 and the downstream
      signaling pathway. The level of inflammatory mediator was quantified using a
      specific ELISA kit. The supernatant of 10 MUg/ml LPS-treated BV2 cells was used
      as conditioned medium (CM). PC12 cells were co-culture with CM for 24 h. Cell
      viability was determined by MTT assay and cell apoptosis was tested by flow
      cytometry. BV2 microglia were treated with 10, 20, or 30 MUg/ml LPS for 24 h. The
      expression of TLR4, MyD88, and NF-kappaB significantly increased. When PC12 cells
      were co-cultured with CM for 24 h, cell viability decreased. CM up-regulated the
      Bax level and down-regulated the Bcl-2 protein level in PC12 cells. PC12 cells
      pretreated with interleukin-1 receptor antagonist (IL-1RA) for 30 min,
      significantly alleviated CM-induced PC12 cell apoptosis. These results suggest
      that BV2 microglia activated by LPS triggered TLR4/MyD88/NF-kappaB signaling
      pathway that induced the release of IL-1beta and could participate in the PC12
      cells injury. 

PMID- 25387797
TI  - The discovery of Hsp70 domain with cell-penetrating activity.
AB  - Chaperone Hsp70 can cross the plasma membrane of living cells using mechanisms
      that so far have not received much research attention. Searching the part of the
      molecule that is responsible for transport ability of Hsp70, we found a cationic
      sequence composed of 20 amino acid residues on its surface, KST peptide, which
      was used in further experiments. We showed that KST peptide enters living cells
      of various origins with the same efficiency as the full-length chaperone. KST
      peptide is capable of carrying cargo with a molecular weight 30 times greater
      than its own into cells. When we compared the membrane-crossing activity of KST
      peptide in complex with Avidin (KST-Av complex) with that of similarly linked
      canonical TAT peptide, we found that TAT peptide penetrated SK-N-SH human
      neuroblastoma cells at a similar rate and efficiency as the KST peptide.
      Furthermore, KST peptide can carry protein complexes consisting of a specific
      antibody coupled to the peptide through the Avidin bridge. An antibody to Hsp70
      delivered to SK-N-SH cells with high expression level of Hsp70 reduced the
      protective power of the chaperone and sensitized the cells to the pro-apoptotic
      effect of staurosporine. We studied the mechanisms of penetration of KST-Av and
      full-length Hsp70 inside human neuroblastoma SK-N-SH and human erythroleukemia K
      562 cells and found that both used an active intracellular transport mechanism
      that included vesicular structures and negatively charged lipid membrane domains.
      Competition analysis of intracellular transport showed that the chaperone reduced
      intracellular penetration of KST peptide and conversely KST peptide prevented
      Hsp70 transport in a dose-dependent manner. 

PMID- 25387799
TI  - Cancer survivors' disclosure of complementary health approaches to physicians:
      the role of patient-centered communication.
AB  - BACKGROUND: Cancer survivors' disclosure of complementary health approaches
      (CHAs) to their follow-up care physicians is necessary to ensure the safe and
      optimal use of such approaches. Rates of disclosure of CHAs are variable and may
      be facilitated by patient-centered communication. METHODS: This cross-sectional
      study conducted in 2003-2004 examined a population-based sample of leukemia,
      colorectal, and bladder cancer survivors (n=623) who were 2 to 5 years after
      their diagnosis. A subset of participants who reported using CHAs (n=196) was
      analyzed with multivariate logistic regression to examine the association between
      patients' perceptions of their physician's patient-centered communication (ie,
      information exchange, affective behavior, knowledge of patients as persons) and
      patients' disclosure of CHA use to their physician with adjustments for
      physician, patient, and patient-physician relationship factors. RESULTS: Thirty
      one percent of the full sample used CHAs, and 47.6% of CHA users disclosed their
      use to their physicians. Disclosure was significantly associated with patient
      centered communication even with adjustments for hypothesized covariates (odds
      ratio [OR], 1.37; 95% confidence interval [CI], 1.09-1.71). Perceived physician
      knowledge of the patient as a person (OR, 1.28; 95% CI, 1.10-1.48) and
      information exchange (OR, 1.27; 95% CI, 1.02-1.60) were the aspects of patient
      centered communication that contributed to this association. The main reason for
      nondisclosure assessed in the survey was that survivors did not think that it was
      important to discuss CHAs (67.0%). A majority of physicians encouraged continued
      use of CHAs when they were disclosed (64.8%). CONCLUSIONS: Results support the
      idea that improving the overall patient centeredness of cancer follow-up care and
      improving the disclosure of CHA use are potentially synergistic clinical goals.

PMID- 25387801
TI  - Wide-range thermochromic luminescence of organoboronium complexes.
AB  - Alkyl-substituted tetra-coordinate organoboronium bisdiketone complexes exhibit
      dramatic luminescence thermochromism in organic solvents. In glass-forming
      alcohols, these complexes exhibit a reversible aqua blue to orange-red to
      greenish yellow luminescence emission colour change upon cooling. 

PMID- 25387800
TI  - Sex classification using the three-dimensional tibia form or shape including
      population specificity approach.
AB  - The aims of this study were to enable geometric morphometric sex classification
      using tibial proximal and distal sexual dimorphism and to evaluate the secular
      trend of tibial shape/form from the early 20th century to the present day. The
      study samples consisted of 61 adult tibias from an early 20th-century Czech
      population and 57 three-dimensional tibias from a 21st-century population.
      Discriminant function analysis with cross-validation was carried out to assess
      the accuracy of sex classification. Shape analysis revealed significant sex
      differences in both tibial extremities of the 21st-century sample and in the
      proximal tibia of the 20th-century population. Sex-based divergence varied
      between the analyzed samples, raising the issues of population specificity and
      diachronic change. Classification using tibial form was more successful than
      using tibial shape. The highest values of correct assignment (91.80% and 88.52%)
      were found using the form from the early 20th Czech population. 

PMID- 25387798
TI  - Ribonucleotides in bacterial DNA.
AB  - In all living cells, DNA is the storage medium for genetic information. Being
      quite stable, DNA is well-suited for its role in storage and propagation of
      information, but RNA is also covalently included in DNA through various
      mechanisms. Recent studies also demonstrate useful aspects of including
      ribonucleotides in the genome during repair. Therefore, our understanding of the
      consequences of RNA inclusion into bacterial genomic DNA is just beginning, but
      with its high frequency of occurrence the consequences and potential benefits are
      likely to be numerous and diverse. In this review, we discuss the processes that
      cause ribonucleotide inclusion in genomic DNA, the pathways important for
      ribonucleotide removal and the consequences that arise should ribonucleotides
      remain nested in genomic DNA. 

PMID- 25387802
TI  - ClinicalTrials.gov reporting: strategies for success at an academic health
      center.
AB  - The Food and Drug Administration Amendments Act of 2007 (FDAAA 2007, US Public
      Law 110-98) mandated registration and reporting of results for applicable
      clinical trials. Meeting these registration and results reporting requirements
      has proven to be a challenge for the academic research community. Duke Medicine
      has made compliance with registration and results reporting a high priority. In
      order to create uniformity across a large institution, a written policy was
      created describing requirements for clinical trials disclosure. Furthermore, a
      centralized resource group was formed with three full time staff members. The
      group not only ensures compliance with FDAAA 2007, it also acts as a resource for
      study teams providing hands-on support, reporting, training, and ongoing
      education. Intensive resourcing for results reporting has been crucial for
      success. Due to implementation of the institutional policy and creation of
      centralized resources, compliance with FDAAA 2007 has increased dramatically at
      Duke Medicine for both registration and results reporting. A consistent
      centralized approach has enabled success in the face of changing agency rules and
      new legislation.

PMID- 25387804
TI  - The A3 adenosine receptor: history and perspectives.
AB  - By general consensus, the omnipresent purine nucleoside adenosine is considered a
      major regulator of local tissue function, especially when energy supply fails to
      meet cellular energy demand. Adenosine mediation involves activation of a family
      of four G protein-coupled adenosine receptors (ARs): A(1), A(2)A, A(2)B, and
      A(3). The A(3) adenosine receptor (A(3)AR) is the only adenosine subtype to be
      overexpressed in inflammatory and cancer cells, thus making it a potential target
      for therapy. Originally isolated as an orphan receptor, A(3)AR presented a
      twofold nature under different pathophysiologic conditions: it appeared to be
      protective/harmful under ischemic conditions, pro/anti-inflammatory, and
      pro/antitumoral depending on the systems investigated. Until recently, the
      greatest and most intriguing challenge has been to understand whether, and in
      which cases, selective A(3) agonists or antagonists would be the best choice.
      Today, the choice has been made and A(3)AR agonists are now under clinical
      development for some disorders including rheumatoid arthritis, psoriasis,
      glaucoma, and hepatocellular carcinoma. More specifically, the interest and
      relevance of these new agents derives from clinical data demonstrating that
      A(3)AR agonists are both effective and safe. Thus, it will become apparent in the
      present review that purine scientists do seem to be getting closer to their goal:
      the incorporation of adenosine ligands into drugs with the ability to save lives
      and improve human health.

PMID- 25387803
TI  - GPIHBP1 missense mutations often cause multimerization of GPIHBP1 and thereby
      prevent lipoprotein lipase binding.
AB  - RATIONALE: GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds
      lipoprotein lipase (LPL) in the subendothelial spaces and shuttles it to the
      capillary lumen. GPIHBP1 missense mutations that interfere with LPL binding cause
      familial chylomicronemia. OBJECTIVE: We sought to understand mechanisms by which
      GPIHBP1 mutations prevent LPL binding and lead to chylomicronemia. METHODS AND
      RESULTS: We expressed mutant forms of GPIHBP1 in Chinese hamster ovary cells, rat
      and human endothelial cells, and Drosophila S2 cells. In each expression system,
      mutation of cysteines in GPIHBP1's Ly6 domain (including mutants identified in
      patients with chylomicronemia) led to the formation of disulfide-linked dimers
      and multimers. GPIHBP1 dimerization/multimerization was not unique to cysteine
      mutations; mutations in other amino acid residues, including several associated
      with chylomicronemia, also led to protein dimerization/multimerization. The loss
      of GPIHBP1 monomers is relevant to the pathogenesis of chylomicronemia because
      only GPIHBP1 monomers-and not dimers or multimers-are capable of binding LPL. One
      GPIHBP1 mutant, GPIHBP1-W109S, had distinctive properties. GPIHBP1-W109S lacked
      the ability to bind LPL but had a reduced propensity for forming dimers or
      multimers, suggesting that W109 might play a more direct role in binding LPL. In
      support of that idea, replacing W109 with any of 8 other amino acids abolished
      LPL binding-and often did so without promoting the formation of dimers and
      multimers. CONCLUSIONS: Many amino acid substitutions in GPIHBP1's Ly6 domain
      that abolish LPL binding lead to protein dimerization/multimerization.
      Dimerization/multimerization is relevant to disease pathogenesis, given that only
      GPIHBP1 monomers are capable of binding LPL.

PMID- 25387805
TI  - Effects of sleep hygiene and artificial bright light interventions on recovery
      from simulated international air travel.
AB  - PURPOSE: Despite the reported detrimental effects of international air travel on
      physical performance, a paucity of interventions have been scientifically tested
      and confirmed to benefit travelling athletes. Consequently, the aim of the
      present study was to examine the effects of sleep hygiene and artificial bright
      light interventions on physical performance following simulated international
      travel. METHODS: In a randomized crossover design, 13 physically active males
      completed 24 h of simulated international travel with (INT) and without (CON) the
      interventions. The mild hypoxia and cramped conditions typically encountered
      during commercial air travel were simulated in a normobaric, hypoxic room.
      Physical performance, subjective jet-lag symptoms and mood states were assessed
      in the morning and evening on the day prior to and for two days post-travel.
      Sleep quantity and quality were monitored throughout each trial. RESULTS: Sleep
      duration was significantly reduced during travel in both trials (P < 0.01),
      though total sleep duration during and following travel was almost significantly
      greater (P = 0.06) in INT (17.0 (16.2-17.8) h) compared to CON (15.7 (14.9-16.5)
      h). Maximal-sprint and countermovement jump (P < 0.05), but not Yo-Yo
      Intermittent Recovery level 1 test (P > 0.05) performance, were significantly
      reduced the evening of day 1 and 2 post-travel, with no differences between
      trials (P > 0.05). Furthermore, vigour was significantly greater (P = 0.04) the
      morning of day 2 in INT [5.3 (3.9-6.7)] compared to CON [2.8 (1.4-4.2)], and
      subjective jet-lag symptoms and mood states were significantly worse on day 2 in
      CON only (P < 0.05). CONCLUSIONS: Whilst reducing travel-induced sleep disruption
      may attenuate travel fatigue, no improvements in the recovery of physical
      performance were apparent.

PMID- 25387806
TI  - Age differences in efficiency of locomotion and maximal power output in well
      trained triathletes.

PMID- 25387807
TI  - Genetic variants in N-myc (and STAT) interactor and susceptibility to glioma in a
      Chinese Han population.
AB  - Glioma is one of the most common and lethal brain tumors. N-myc (and STAT)
      interactor (NMI) gene has been reported in tumorigenesis, and our previous study
      further showed its implication in glioma progression. To elucidate its
      involvement in the etiology of glioma, we conducted a case-control study of 875
      patients and 1040 controls in a Chinese Han population by genotyping 7
      representative single nucleotide polymorphisms (SNPs) in NMI. Allele and genotype
      frequency distribution of five loci (rs2278089, rs2194492, rs6734376, rs3854012,
      and rs11730) were significantly different between the cases and controls.
      Unconditional logistic regression showed that the variant genotypes of rs2278089
      [adjusted odds ratio (OR) = 1.57, P = 4.23 * 10(-6)], rs2194492 (adjusted OR =
      1.49, P = 1.20 * 10(-4)), and rs6734376 (adjusted OR = 0.06, P = 8.65 * 10(-13))
      significantly affected glioma risk compared with the major homozygotes, while the
      minor homozygotes of rs3854012 (adjusted OR = 0.54, P = 4.64 * 10(-6)) and
      rs11730 (adjusted OR = 0.60, P = 1.50 * 10(-4)) showed significant protective
      effects. Further stratified analyses indicated that these associations remained
      significant in subgroups of low-grade glioma (LGG) and high-grade glioma (HGG).
      Additionally, haplotype and diplotype analyses showed consistent results. The
      Bonferroni correction was applied for all these analyses. Moreover, luciferase
      reporter gene assays revealed enhanced promoter activity of the C risk allele of
      rs2194492 in several cell lines compared with the G major allele, suggesting its
      potential function in transcriptional activation of NMI. Taken together, these
      results revealed that NMI polymorphisms may contribute to genetic susceptibility
      to glioma.

PMID- 25387808
TI  - The efficacy and safety of bevacizumab combined with chemotherapy in treatment of
      HER2-negative metastatic breast cancer: a meta-analysis based on published phase
      III trials.
AB  - Bevacizumab (Bev) combined with chemotherapy significantly improves progression
      free survival (PFS) but not overall survival (OS) in patients with human
      epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer
      (MBC). The efficacy and safety depend on the type of chemotherapy combined with
      Bev. We performed a meta-analysis of phase III trials to evaluate the efficacy
      and safety of Bev + standard chemotherapy for HER2-negative MBC. The Cochrane
      Central Register of Controlled Trials, the Cochrane databases, EMBASE, MEDLINE,
      and ClinicalTrials.gov were analyzed. The primary outcomes included PFS, OS, and
      toxicity. Event-based hazard ratios (HRs) and relative risks (RRs) were expressed
      with the 95% confidence intervals (CIs). Four randomized controlled trials
      consisting of 3082 patients were included. Bev + standard chemotherapy improved
      PFS (HR 0.70, CI 0.64-0.77, P = 0.000) but had no effect on OS (HR 0.92, CI 0.82
      1.02, P = 0.119). Bev + chemotherapy increased the incidence of febrile
      neutropenia (RR 1.45, CI 1.00 to 2.09, P = 0.048), proteinuria (RR 11.68, CI 3.72
      36.70, P = 0.000), sensory neuropathy (RR 1.33, CI 1.05-1.70, P = 0.020), and
      grade >=3 hypertension (RR 13.94, CI 7.06-27.55, P = 0.000). No differences in
      efficacy were observed between Bev + paclitaxel and Bev + capecitabine (Cape),
      but Bev + Cape increased the incidence of neutropenia. Bev + standard
      chemotherapy improved PFS in HER2-negative MBC patients. No benefit in OS was
      observed. Bev + Cape and Bev + paclitaxel had similar treatment efficacy, but Bev
      + Cape had a higher incidence of neutropenia.

PMID- 25387809
TI  - beta1 integrin mediates colorectal cancer cell proliferation and migration
      through regulation of the Hedgehog pathway.
AB  - beta1 integrin (ITGB1) is the major expressed integrin protein of normal cells
      and tumor-associated cells. It is often up-regulated in human malignancies and is
      involved in many developmental processes, such as tumor progression and
      metastasis. However, little is known about the function of ITGB1 in colorectal
      cancer. We constructed lentiviral vectors expressing ITGB1 or ITGB1-specific RNA
      interference (RNAi) and an unrelated control vector. After infecting HT29 cells
      in vitro, proliferation and migration were evaluated by Cell Counting Kit 8 (CCK
      8) assays, transwell invasion assays, and Western blots. The influence of
      lentivirus infection on the tumor development capacity of HT29 cells in vivo was
      examined by xenografting the tumor cells. The expression of ITGB1 in the
      xenografted tumor cells was analyzed by immunohistochemistry. The up-regulation
      of ITGB1 significantly increased the proliferation in HT29 cells in vitro.
      Moreover, we found that the overexpression of ITGB1 up-regulated sonic hedgehog
      (Shh) while down-regulating Gli1 and SuFu in HT29-ITGB1 cells compared to
      controls. Moreover, the levels of c-myc and cyclin D1 proteins were up-regulated.
      Transwell assays showed that the number of migrating HT29-RNAi cells was lower
      than that in the other cell groups, indicating that ITGB1 significantly enhances
      the invasive ability of HT29 cells. In addition to these in vitro results, ITGB1
      was found to be a significantly effective growth factor in a xenografted tumor
      mouse model. These results suggest that ITGB1 induces growth and invasion in a
      human colorectal cancer cell line through the hedgehog (Hh) signaling pathway in
      vitro and in vivo. 

PMID- 25387810
TI  - Association of interleukin 22 polymorphisms with gastric cancer risk.
AB  - Interleukin (IL)-22 has been implicated in inflammation and tumorigenesis. To
      date, no studies have investigated the role of IL-22 polymorphism in the
      carcinogenesis of gastric cancer (GC). In this study, we aimed to investigate the
      association of IL-22 polymorphisms with the risk of GC in a Chinese population.
      One hundred eight GC patients and 110 healthy controls were included in the
      study. IL-22 rs1179251, rs2227485, and rs2227473 polymorphisms were determined by
      PCR amplification and DNA sequencing. Haplotypes were constructed, and a possible
      association of these haplotypes with GC was assessed. The distribution of IL-22
      rs1179251 polymorphism with clinical parameters was also analyzed. The IL-22
      rs1179251 polymorphism was significantly associated with an increased risk of GC
      (p < 0.05). Stratified analysis revealed that rs1179251 was associated with
      advanced stages, lymph node metastases, and distant metastases of GC (p < 0.05).
      No associations were found between rs2227485 and rs2227473 and the risk of GC (p
      > 0.05). Three possible haplotypes (C(rs1179251)-C(rs2227485)-G(rs2227485),
      C(rs1179251)-T(rs2227485)-G(rs2227485), and G(rs1179251)-T(rs2227485)
      A(rs2227485)) were identified, but no associations were found between these and
      the risk of GC (p > 0.05). In summary, our study demonstrates that the rs1179251
      polymorphism of IL-22 was associated with an increased risk of GC and may
      influence the progression of GC. Future larger studies with other ethnic
      populations are required to confirm these findings.

PMID- 25387811
TI  - Distal acquired demyelinating symmetric (DADS) neuropathy associated with
      colorectal adenocarcinoma.
AB  - INTRODUCTION: Paraneoplastic neuropathies are well recognized as a remote effect
      of cancer, and subacute sensory neuronopathy is a recognized syndrome.
      Demyelinating neuropathies are relatively rare. Distal acquired demyelinating
      symmetric (DADS) neuropathy associated with lymphoproliferative disease has been
      reported previously. We present the association of DADS neuropathy with solid
      tumor. METHODS: We report the clinical presentation, electrophysiology, and
      progress of DADS neuropathy in a patient later found to have colorectal
      adenocarcinoma. RESULTS: A patient presented with subacute onset of symmetric
      distal sensory and motor symptoms. Electrophysiology was typical of DADS
      neuropathy. Anti-MAG antibodies were initially positive at low titer, and
      indirect immunofluorescence analysis for anti-nuclear antibodies revealed
      autoantibodies to centromere nuclear protein-F (CENP-F). There was clinical and
      electrophysiologic resolution after tumor resection. CONCLUSIONS: This case
      describes the presentation of DADS neuropathy as a paraneoplastic syndrome in a
      patient later found to have colorectal adenocarcinoma.

PMID- 25387812
TI  - The Essence of Eddie: a reflection of the interplay between art, relationships,
      and emotion.

PMID- 25387813
TI  - MLL gene amplification in acute myeloid leukemia and myelodysplastic syndromes is
      associated with characteristic clinicopathological findings and TP53 gene
      mutation.
AB  - MLL gene rearrangements are well-recognized aberrations in acute myeloid leukemia
      (AML) and myelodysplastic syndromes (MDS). In contrast, MLL gene amplification in
      AML/MDS remains poorly characterized. Here, we report a series of 21 patients
      with myeloid neoplasms associated with MLL gene amplification from 1 institution.
      This series included 13 men and 8 women, with a median age of 64 years. Eleven
      patients presented as AML with myelodysplasia-related changes, 6 as therapy
      related AML, and 4 as therapy-related MDS. All patients had a highly complex
      karyotype, including frequent -5/del(5q), -18, and -17/del(17p) abnormalities; 16
      patients were hypodiploid. TP53 mutations were detected in all 12 patients
      tested, and 3 patients showed TP53 mutation before MLL amplification.
      Morphologically, the leukemic cells frequently showed cytoplasmic vacuoles,
      bilobed nuclei, and were associated with background dyspoiesis.
      Immunophenotypically, 15 patients had a myeloid and 4 had myelomonocytic
      immunophenotype. Laboratory coagulopathies were common; 7 patients developed
      disseminated intravascular coagulopathy, and 3 died of intracranial bleeding. All
      patients were refractory to therapy; the median overall survival was 1 month,
      after MLL gene amplification was detected. We concluded that AML/MDS with MLL
      gene amplification is likely a subset of therapy-related AML/MDS or AML with
      myelodysplasia-related changes, associated with distinct clinicopathological
      features, frequent disseminated intravascular coagulopathy, a highly complex
      karyotype, TP53 deletion/mutation, and an aggressive clinical course. 

PMID- 25387814
TI  - Elaboration of tubules with active hedgehog drives parenchymal fibrogenesis in
      gestational alloimmune liver disease.
AB  - Gestational alloimmune liver disease (GALD) produces severe neonatal liver
      disease that is notable for paucity of hepatocytes, large numbers of parenchymal
      tubules, and extensive fibrosis. Liver specimens from 19 GALD cases were studied
      in comparison with 14 infants without liver disease (normal newborn liver; NNL)
      to better understand the pathophysiology that would produce this characteristic
      histopathology. GALD liver parenchyma contained large numbers of tubules
      comprising epithelium expressing KRT7/19, EPCAM, and SOX9, suggesting biliary
      progenitor status. Quantitative morphometry demonstrated that in GALD, the area
      density of KRT19+ tubules was 16.4 +/- 6.2 versus 2.0 +/- 2.6 area% in NNL (P <
      .0001). Functional hepatocyte mass was markedly reduced in GALD, 16.3 +/- 6.2
      versus 61.9 +/- 11.0 area% of CPS1+ cells in NNL (P < .0001). A strong inverse
      correlation was established between CPS1+ area density and KRT19+ area density
      (r(2) = 0.66, P < .0001). Tubules showed active hedgehog signaling as determined
      by SHH and nuclear GLI2 expression and expressed the profibrogenic cytokine SPP1.
      SPP1 protein content and SPP1 expression were greater in GALD than NNL (15- and
      13-fold respectively; P = .002). GALD liver contained large numbers of activated
      myofibroblasts and showed greater than 10-fold more fibrosis than NNL. The extent
      of fibrosis correlated with the area density of KRT19+ tubules (r(2) = 0.387, P =
      .001). The data support a pathogenic model in which immune injury to fetal
      hepatocytes provides a stimulus for expansion of parenchymal tubules, which, by
      way of Hh activation, produce fibrogenic signals leading to vibrant fibrosis.

PMID- 25387815
TI  - Temporal trends in cardiac arrest incidence and outcome in Finnish intensive care
      units from 2003 to 2013.
AB  - PURPOSE: To estimate temporal trends in incidence and hospital mortality after
      cardiac arrest in Finnish intensive care units. METHODS: Using a large nationwide
      intensive care unit (ICU) database we identified patients suffering from cardiac
      arrest following ICU admission (ICU-CA) during the study period (2003-2013). ICU
      CA was defined as need for cardiopulmonary resuscitation and/or defibrillation
      (non-arrest cardioversions were excluded) according to the Therapeutic
      Intervention Scoring System-76. Patients admitted with an admission diagnosis of
      cardiac arrest were excluded. We determined crude incidence and risk-adjusted
      hospital mortality (based on a customized severity of illness model) for all ICU
      CA patients, and for predefined admission diagnosis subgroups. Temporal trends
      for the observed period were calculated for crude incidence and risk-adjusted
      hospital mortality. RESULTS: Crude incidence for all ICU-CA patients was 29/1,000
      ICU admissions, with the highest incidence 118/1,000 in the non-operative
      cardiovascular subgroup. Overall hospital mortality for ICU-CA patients was 55.5%
      [95% confidence interval (CI) 54-57%]. Hospital mortality was 53.1% (95% CI 50.4
      55.8%) for non-operative cardiovascular ICU-CA patients, 32.9% (95% CI 26.9
      38.9%) for post cardiac surgery ICU-CA patients, and 56.3% (95% CI 51.2-61.3%)
      for neurological/neurosurgical ICU-CA patients. There was a significant reduction
      in the overall ICU-CA incidence and in the risk-adjusted hospital mortality of
      ICU-CA and non-cardiac arrest cases (non-CA) over the observed study period (p <
      0.001). CONCLUSION: Our data suggest that the incidence of ICU-CA has decreased
      in Finnish ICUs between 2003 and 2013. Similar reduction in hospital mortality
      over time was observed for both ICU-CA and non-CA populations.

PMID- 25387816
TI  - Sudden death in ICU: the Finnish experience.

PMID- 25387817
TI  - Biomarkers for AKI improve clinical practice: yes.

PMID- 25387818
TI  - Biomarkers for AKI improve clinical practice: no.

PMID- 25387819
TI  - Teaching medical students to talk about death and dying in the ICU: feasibility
      of a peer-tutored workshop.

PMID- 25387820
TI  - Polyelectrolyte-coated gold nanorods and their biomedical applications.
AB  - Gold nanorods (GNRs) have been extensively used in biomedical applications,
      because of their favourable optical properties. Their longitudinal surface
      plasmon resonance can be tuned, providing a strong near-infrared (NIR) extinction
      coefficient peak within the tissue transparency window. However, the modification
      of the surface of GNRs is essential before they can be used for biomedical
      applications. The number of GNRs taken up by cells and their biodistribution
      depend on their surface modification. Here, we review the recent advances in
      modifying GNR surfaces with polyelectrolytes for biomedical applications. Major
      polyelectrolytes used to coat GNR surfaces over the past few years and the
      biocompatibility of polyelectrolyte-coated GNRs are discussed. 

PMID- 25387821
TI  - Impact of roux-en Y gastric bypass surgery on prognostic factors of type 2
      diabetes mellitus: meta-analysis and systematic review.
AB  - Our aim is to clarify the features of complete type 2 diabetes mellitus (T2DM)
      remission in patients who undergo Roux-en Y gastric bypass surgery, to better
      determine factors affecting the outcome of T2DM surgery. A search was conducted
      for original studies on Medline, PubMed and Elsevier from inception until October
      28, 2014. All of the articles included in this study were assessed with the
      application of predetermined selection criteria and were divided into two groups:
      Roux-en Y gastric bypass surgery for T2DM patients in remission or non-remission.
      The meta-analysis results demonstrated that fasting C-peptide values were
      significantly associated with increased remission (C-peptide: 95%CI = 0.2-1.0)
      whereas T2DM duration, patient age, preoperative insulin use, preoperative
      fasting blood glucose values and preoperative glycosylated haemoglobin values
      were significantly associated with reduced remission (T2DM duration: 95%CI = -1.2
      - -0.7; age: 95%CI = -0.5 - -0.1; percentage of preoperative insulin users: odd
      ratio = 0.10, 95%CI = 0.07-0.15; preoperative fasting blood glucose: 95%CI = -0.9
      - -0.5; preoperative glycosylated haemoglobin: 95%CI = -1.1 - -0.4). However, the
      results demonstrated that body mass index was not statistically different (body
      mass index: 95%CI = -0.2-0.6). The results of the systematic review demonstrated
      that smaller waist circumference; lower total cholesterol, triglycerides and low
      density lipoprotein levels, increased higher high-density lipoprotein levels,
      shorter cardiovascular disease history and less preoperative prevalence of
      hypertension contribute to the increased postoperative remission rate. Better
      results are obtained in younger patients with less severe diabetes, a smaller
      waist circumference, higher preoperative high-density lipoprotein, lower
      preoperative total cholesterol, triglycerides and low-density lipoprotein levels
      and fewer other complications of shorter durations.

PMID- 25387822
TI  - Safety of dabigatran in an elderly population: single center experience in Italy.
AB  - In clinical practice, adherence to drugs and their safety may differ from
      randomised controlled trial settings. This study was undertaken to investigate
      the adherence to dabigatran, a direct thrombin inhibitor, and its safety in a
      real-world setting. We studied a prospective cohort of 114 elderly consecutive
      patients with non valvular atrial fibrillation (AF) who were treated with
      dabigatran 150 mg twice-daily (N=39) or 110 mg twice-daily (N=76). These patients
      were studied at baseline and after an average of 6 months. Mean age was 80 years
      and 53% were women. At entry, the average CHA2DS2VASc score was 4 and the HAS
      BLED score was 2. AF was permanent in 49% of patients, persistent in 30%,
      paroxysmal in 12% and new-onset in 24%. In the follow-up clinical visit we
      ascertained vital status, adherence to treatment according to refill prescription
      orders, and side effects. Adherence was >=80% in 76.5% of patients. Heartburn,
      the most frequent adverse effect, was reported by 25 patients (22%). Major and
      minor bleedings were experienced by 2 (1.8%) and 9 (7.9%) patients, respectively.
      Permanent discontinuation occurred in 18 patients (16%). The most frequent cause
      of permanent discontinuation was heartburn (10 patients). This real-life study
      suggests that safety of dabigatran and adherence to this drug in an elderly
      cohort of AF patients at high or very high risk of thromboembolism are generally
      good. Heartburn is the main cause of treatment discontinuation.

PMID- 25387823
TI  - Pain intensity as prognostic factor in cancer pain management.
AB  - AIM: The aim of this study was to prospectively assess the prognostic value of
      initial pain intensity and its duration in advanced cancer patients. METHODS: A
      prospective study was conducted in a sample of patients with cancer requiring
      pain control. Patients underwent standard analgesic strategies used in our
      palliative care units. Pain intensity was measured at admission (T0) and after
      successful dose titration or opioid/route switching within a week (Ts). Patients
      were also asked about their pain intensity reported 15 days before admission (T
      15). Doses of opioids and duration of opioid use were recorded. Patients were
      also assessed for the presence of incident pain, neuropathic pain, alcoholism,
      delirium, and symptom intensity, including items representing psychological
      distress. One week after or at time of stabilization (Ts), the opioid response
      was clinically graded as follows: (1) good pain control; (2) adequate pain
      control requiring more aggressive opioid escalation; (3) adequate pain control
      associated with the occurrence of adverse effects; (4) incapacity to achieve pain
      control within a week. Opioid escalation indexes and days for dose finding were
      also recorded. RESULTS: Pain intensity at T0 and at T-15, opioid doses, duration
      of opioid therapy, and age were associated with more complex analgesic therapies,
      which were effective in almost all patients within a week. CONCLUSION: High
      levels of pain intensity, often due to previous undertreatment, are predictive of
      more complex analgesic treatment. Opioid tolerance, as well as younger age, may
      also play a role.

PMID- 25387824
TI  - Left ventricular mass and progenitor cells in chronic heart failure patients.
AB  - The aim of the study was to evaluate the association between circulating (CPCs)
      and endothelial (EPCs) progenitor cells and left ventricular (LV) remodeling in
      chronic heart failure (HF). 85 HF patients, ranging 29-89 years, 83.5% males,
      45.9% ischemic, NYHA functional class II-IV, with a LV ejection fraction <=40%
      were studied. LV ejection fraction, LV end-diastolic and end-systolic (LVESV)
      volumes, LV mass and tricuspid annular plane systolic excursion (TAPSE) were
      evaluated, and, when indicated, indexed for body surface area (BSA). CPCs and
      EPCs number was assessed using flow cytometry. CPCs were defined as CD34+, CD133+
      and CD34+/CD133+. EPCs, identified through their expression of KDR, were defined
      as CD34+/KDR+, CD133+/KDR+ and CD34+/CD133+/KDR+. All EPCs were negatively
      related to LVESV/BSA (r = -0.24, p = 0.02 for all EPC's populations), and to
      LVmass/BSA (CD34+KDR+; r = -0.30, p = 0.005; CD133+KDR+; r = -0.31, p = 0.004;
      CD34+CD133+KDR+; r = -0.29, p = 0.007). No differences in EPCs levels in relation
      to cardiovascular risk factors, medications, etiology, age or gender were
      observed. CPCs number was higher in women, and lower in ischemic patients. In
      logistic regression analyses, the low EPCs' number was associated with an
      increased likelihood of abnormal LVmass/BSA. CPCs proved to be higher and EPCs
      lower in patients with severely abnormal LVmass/BSA (gr/m(2), >=122 in women and
      >=149 in men). Our results suggest a correlation between LV remodeling and
      progenitor cells. This is noteworthy considering that it has been suggested that
      bone marrow-derived EPCs participate in cardiac regeneration and function
      recovery in the setting of progressive HF.

PMID- 25387825
TI  - A case of PRES in an active lupus nephritis patient after treatment of
      corticosteroid and cyclophosphamide.
AB  - Posterior reversible encephalopathy syndrome (PRES) is primarily a radiological
      diagnosis. The syndrome is characterized by headache, altered mental status,
      seizures, and bilateral posterior white matter edema in a nonvascular
      distribution on neuroimaging with resolution of findings usually in 7-14 days
      (Casey et al. in AJNR Am J Neuroradiol 21:1199-1206, 2000). In most cases,
      computed tomography of the brain will show hypodense lesions in the parieto
      occipital lobe. Although this syndrome is uncommon, prompt and accurate
      recognition allows early treatment, which has been shown to produce favorable
      outcomes. It is hypothesized that the dysfunction can be caused by a failure of
      autoregulation systemic hypertension or by the cytotoxic effects of vasculitides
      and immunosuppressive drugs. The present report is a possible second case of
      cyclophosphamide-induced PRES in a 16-year-old girl with systemic lupus
      erythematous and lupus nephritis. The initial suspected diagnosis was an ischemic
      stroke, but it was later changed, with resolution of symptoms after management of
      the underlying cause.

PMID- 25387826
TI  - Electroacupuncture improves cerebral blood flow and attenuates moderate ischemic
      injury via Angiotensin II its receptors-mediated mechanism in rats.
AB  - BACKGROUND: To investigate the effects and potential mechanism of
      electroacupuncture intervention on expressions of Angiotensin II and its
      receptors-mediated signaling pathway in experimentally induced cerebral ischemia.
      METHODS: Totally 126 male Wistar rats were randomly divided into control group,
      model group and EA group. The latter two were further divided into ten subgroups
      (n = 6) following Middle Cerebral Artery Occlusion (MCAO). Changes in regional
      cerebral blood flow (rCBF) and expressions of Angiotensin II and its receptors
      (AT1R, AT2R), as well as effector proteins in phosphatidyl inositol signal
      pathway were monitored before and at different times after MCAO. RESULTS: MCAO
      induced decline of ipsilateral rCBF was partially suppressed by
      electroacupuncture, and contralateral blood flow was also superior to that of
      model group. Angiotensin II level was remarkably elevated immediately after MCAO,
      while electroacupuncture group exhibited significantly lower levels at 1 to 3 h
      and the value was significantly increased thereafter. The enhanced expression of
      AT1R was partially inhibited by electroacupuncture, while increased AT2R level
      was further induced. Electroacupuncture stimulation attenuated and postponed the
      upregulated-expressions of Gq and CaM these upregulations. ELISA results showed
      sharply increased expressions of DAG and IP3, which were remarkably neutralized
      by electroacupuncture. CONCLUSIONS: MCAO induced significant increases in
      expression of Angiotensin II and its receptor-mediated signal pathway. These
      enhanced expressions were significantly attenuated by electroacupuncture
      intervention, followed by reduced vasoconstriction and improved blood supply in
      ischemic region, and ultimately conferred beneficial effects on cerebral
      ischemia.

PMID- 25387827
TI  - Expression of MTAP inhibits tumor-related phenotypes in HT1080 cells via a
      mechanism unrelated to its enzymatic function.
AB  - Methylthioadenosine Phosphorylase (MTAP) is a tumor suppressor gene that is
      frequently deleted in human cancers and encodes an enzyme responsible for the
      catabolism of the polyamine byproduct 5'deoxy-5'-methylthioadenosine (MTA). To
      elucidate the mechanism by which MTAP inhibits tumor formation, we have
      reintroduced MTAP into MTAP-deleted HT1080 fibrosarcoma cells. Expression of MTAP
      resulted in a variety of phenotypes, including decreased colony formation in soft
      agar, decreased migration, decreased in vitro invasion, increased matrix
      metalloproteinase production, and reduced ability to form tumors in severe
      combined immunodeficiency mice. Microarray analysis showed that MTAP affected the
      expression of genes involved in a variety of processes, including cell adhesion,
      extracellular matrix interaction, and cell signaling. Treatment of MTAP
      expressing cells with a potent inhibitor of MTAP's enzymatic activity (MT-DADMe
      ImmA) did not result in a MTAP- phenotype. This finding suggests that MTAP's
      tumor suppressor function is not the same as its known enzymatic function. To
      confirm this, we introduced a catalytically inactive version of MTAP, D220A, into
      HT1080 cells and found that this mutant was fully capable of reversing the soft
      agar colony formation, migration, and matrix metalloproteinase phenotypes. Our
      results show that MTAP affects cellular phenotypes in HT1080 cells in a manner
      that is independent of its known enzymatic activity. 

PMID- 25387828
TI  - Developmental ethanol exposure leads to dysregulation of lipid metabolism and
      oxidative stress in Drosophila.
AB  - Ethanol exposure during development causes an array of developmental
      abnormalities, both physiological and behavioral. In mammals, these abnormalities
      are collectively known as fetal alcohol effects (FAE) or fetal alcohol spectrum
      disorder (FASD). We have established a Drosophila melanogaster model of FASD and
      have previously shown that developmental ethanol exposure in flies leads to
      reduced expression of insulin-like peptides (dILPs) and their receptor. In this
      work, we link that observation to dysregulation of fatty acid metabolism and
      lipid accumulation. Further, we show that developmental ethanol exposure in
      Drosophila causes oxidative stress, that this stress is a primary cause of the
      developmental lethality and delay associated with ethanol exposure, and, finally,
      that one of the mechanisms by which ethanol increases oxidative stress is through
      abnormal fatty acid metabolism. These data suggest a previously uncharacterized
      mechanism by which ethanol causes the symptoms associated with FASD. 

PMID- 25387831
TI  - Peritoneal encapsulation as a cause for recurrent abdominal pain in a 16-year-old
      male.

PMID- 25387830
TI  - Biochemical and structural characterization of the apicoplast dihydrolipoamide
      dehydrogenase of Plasmodium falciparum.
AB  - PDC (pyruvate dehydrogenase complex) is a multi-enzyme complex comprising an E1
      (pyruvate decarboxylase), an E2 (dihydrolipomide acetyltransferase) and an E3
      (dihydrolipoamide dehydrogenase). PDC catalyses the decarboxylation of pyruvate
      and forms acetyl-CoA and NADH. In the human malaria parasite Plasmodium
      falciparum, the single PDC is located exclusively in the apicoplast. Plasmodium
      PDC is essential for parasite survival in the mosquito vector and for late liver
      stage development in the human host, suggesting its suitability as a target for
      intervention strategies against malaria. Here, PfaE3 (P. falciparum apicoplast
      E3) was recombinantly expressed and characterized. Biochemical parameters were
      comparable with those determined for E3 from other organisms. A homology model
      for PfaE3 reveals an extra anti-parallel beta-strand at the position where human
      E3BP (E3-binding protein) interacts with E3; a parasite-specific feature that may
      be exploitable for drug discovery against PDC. To assess the biological role of
      Pfae3, it was deleted from P. falciparum and although the mutants are viable,
      they displayed a highly synchronous growth phenotype during intra-erythrocytic
      development. The mutants also showed changes in the expression of some
      mitochondrial and antioxidant proteins suggesting that deletion of Pfae3 impacts
      on the parasite's metabolic function with downstream effects on the parasite's
      redox homoeostasis and cell cycle. 

PMID- 25387832
TI  - The stability and electronic properties of novel three-dimensional graphene-MoS2
      hybrid structure.
AB  - Three-dimensional (3D) hybrid layered materials receive a lot of attention
      because of their outstanding intrinsic properties and wide applications. In this
      work, the stability and electronic structure of three-dimensional graphene-MoS2
      (3 DGM) hybrid structures are examined based on first-principle calculations. The
      results reveal that the 3 DGMs can easily self-assembled by graphene nanosheet
      and zigzag MoS2 nanoribbons, and they are thermodynamically stable at room
      temperature. Interestingly, the electronic structures of 3 DGM are greatly
      related to the configuration of joint zone. The 3 DGM with odd-layer thickness
      MoS2 nanoribbon is semiconductor with a small band gap of 0.01-0.25 eV, while the
      one with even-layer thickness MoS2 nanoribbon exhibits metallic feature. More
      importantly, the 3 DGM with zigzag MoS2 nanoribbon not only own the large surface
      area and effectively avoid the aggregation between the different nanoribbons, but
      also can remarkably enhance Li adsorption interaction, thus the 3 DGM have the
      great potential as high performance lithium ion battery cathodes.

PMID- 25387833
TI  - Olfactomedin-4 autoantibodies give unusual c-ANCA staining patterns with
      reactivity to a subpopulation of neutrophils.
AB  - Testing for the presence of ANCAs in circulation is part of the clinical
      examinations routinely performed upon suspected autoimmune disorders, mainly
      vasculitis. The autoantibodies are typically directed toward neutrophil MPO or
      PR3. These are major granule-localized proteins, and similar to all hitherto
      described ANCA antigens, they are expressed by all neutrophils, and ANCA
      containing sera thus give rise to uniform reactivity toward all neutrophils in a
      sample. In this paper, we describe sera from 2 unrelated patients with diffuse
      inflammatory symptoms that gave rise to peculiar c-ANCA patterns, only reacting
      with a subpopulation (roughly 30%) of human neutrophils. By immunoblotting, both
      sera reacted to the same antigen, which was expressed in intracellular granules.
      The antigen could be released to the extracellular milieu through secretion but
      also through the formation of NETs. Neutrophils have long been considered a
      homogenous cell population, but it is becoming increasingly clear that distinct
      subpopulations, defined by the presence or absence of certain proteins, exist.
      One such marker that defines a neutrophil subset is the granule protein OLFM4.
      The unusual, subset-restricted c-ANCA sera reacted only with OLFM4-positive
      neutrophils, and MS analysis revealed that the autoantigen was, in fact, OLFM4.
      These data describe for the first time a c-ANCA pattern reactive to only a
      subpopulation of neutrophils and identify the granule protein OLFM4 as a novel
      autoantigen. 

PMID- 25387835
TI  - CD8+ CD122+ PD-1- effector cells promote the development of diabetes in NOD mice.
AB  - It is well established that CD4 and CD8 T cells are required for the initiation
      of autoimmune diabetes in NOD mice. However, different subsets of CD4 or CD8
      cells may play different roles in the initiation of insulitis. In this study, we
      evaluated the role of the previously described CD8(+) CD122(+) in this process.
      We found that prediabetic NOD mice have an almost 50% reduction of CD8(+)
      CD122(+) T cells in their secondary lymphoid organs compared with BL/6 or Balb/c
      mouse strains. This reduction is explained by the lack of the regulatory CD8(+)
      CD122(+) PD-1(+) cell population in the NOD mice, as we found that all CD8(+)
      CD122(+) T cells from prediabetic NOD mice lack PD-1 expression and regulatory
      function. Depletion of CD8(+) CD122(+) PD-1(-) cells through injection of anti
      CD122 mAb in prediabetic female NOD mice reduced the infiltration of mononuclear
      cells into the Langerhans islets and delayed the onset and decreased the
      incidence of overt diabetes. In addition, we found that transfer of highly
      purified and activated CD8(+) CD122(+) PD-1(-) cells, together with diabetogenic
      splenocytes from NOD donors to NOD SCID recipients, accelerates the diabetes
      development in these mice. Together, these results demonstrate that CD8(+)
      CD122(+) PD-1(-) T cells from NOD mice are effector cells that are involved in
      the pathogenesis of autoimmune diabetes. 

PMID- 25387834
TI  - Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T
      cell antigen receptor in human T cells.
AB  - TCR-induced signaling controls T cell activation that drives adaptive immunity
      against infections, but it can also induce dysfunctional T cell responses that
      promote pathologic disease. The PI3K pathway regulates many downstream effector
      responses after TCR stimulation. However, the molecular mechanisms that induce
      PI3K function downstream of the TCR are not fully understood. We have previously
      shown that Pyk2 is activated downstream of the TCR in a PI3K-independent manner.
      Although Pyk2 controls adhesion, proliferation, and cytokine production in T
      cells, the mechanisms by which it controls these processes are not known. In this
      study, we generated Pyk2-deficient human T cells to elucidate further the role
      that this kinase plays in TCR-induced effector functions and signaling. We
      observed that Pyk2 localized with the p85 regulatory subunit of PI3K at the LAT
      complex and that PI3K-dependent signaling was impaired in Pyk2-deficient T cells.
      Likewise, functions downstream of PI3K, including IFN-gamma production and
      proliferation, were also suppressed in human T cells deficient in Pyk2.
      Collectively, these data demonstrate that Pyk2 is a critical regulator of PI3K
      function downstream of the TCR. 

PMID- 25387836
TI  - Adenosine stimulates angiogenesis by up-regulating production of thrombospondin-1
      by macrophages.
AB  - Increase of blood capillary density at the interface between normal and ischemic
      tissue after acute MI reduces infarct size and improves cardiac function. Cardiac
      injury triggers the production of the matricellular component TSP-1, but its role
      in angiogenesis is not clear, as both anti- and proangiogenic properties have
      been reported. It is unknown whether TSP-1 is modulated by other factors released
      during cardiac injury. Among these, Ado is a well-known promoter of angiogenesis.
      This study determined whether Ado modulates TSP-1 expression and the implication
      on angiogenesis. Ado dose dependently increased the production of TSP-1 by human
      macrophages. With the use of agonists and antagonists of AdoRs, coupled to RNA
      interference, we observed that this effect is mediated via A2AR and A2BR. The Ado
      effect was reproduced by cholera toxin (Gs protein activator) and forskolin
      (adenylate cyclase activator) and blocked by the PKA inhibitor H89. Conditioned
      medium from Ado-treated macrophages stimulated microvessel outgrowth from aortic
      ring explants by 400%, and induced vessel formation in matrigel plugs.
      Microvessel outgrowth and vessel formation were blocked completely by addition of
      anti-TSP-1 antibodies to conditioned medium. Chronic administration of Ado to
      rats after MI maintained long-term expression of TSP-1 in the infarct border
      zone, and this was associated with enhanced border-zone vascularization. Ado up
      regulates TSP-1 production by macrophages, resulting in stimulation of
      angiogenesis. The mechanism involves A2AR and A2BR and is mediated through the
      cAMP/PKA pathway. This information may be important when designing Ado-based
      therapies of angiogenesis. 

PMID- 25387838
TI  - NovoSeven (recombinant factor VIIa) for the treatment of bleeding episodes and
      perioperative management in patients with Glanzmann's thrombasthenia.
AB  - Glanzmann's thrombasthenia is a rare inherited autosomal recessive bleeding
      disorder caused by qualitative or quantitative defects of the platelet membrane
      glycoprotein IIb/IIIa. The ensuing lack of platelet aggregation is frequently
      associated with mucocutaneous bleeding that may be variable in both frequency and
      intensity, ranging from minimal bruising to severe and life-threatening
      hemorrhages. A number of treatment modalities have been proposed to manage the
      bleeding episodes, which include local measures, antifibrinolytic agents,
      platelet transfusions and recombinant activated factor VII. The role of this
      bypassing hemostatic agent for treatment or prevention of bleeding episodes in
      Glanzmann's thrombasthenia patients is critically analyzed in this review. 

PMID- 25387837
TI  - Ibrutinib: a paradigm shift in management of CLL.
AB  - B-cell receptor (BCR) signaling plays a vital role in B-cell malignancies; Bruton
      tyrosine kinase is a critical mediator of this signaling. BCR signaling, either
      constitutively or following antigen binding, leads to activation of several
      downstream pathways involved in cell survival, proliferation and migration. The
      efficacy observed in studies of the Bruton tyrosine kinase inhibitor, ibrutinib,
      confirms that BCR signaling is critical for the growth of B-cell malignancies.
      Ibrutinib characteristically induces redistribution of malignant B cells from
      tissues into the peripheral blood and rapid resolution of adenopathy.
      Furthermore, ibrutinib therapy results in normalization of lymphocyte counts and
      improvement in cytopenias. Ibrutinib has been shown to have an excellent safety
      profile and does not cause myelosuppression. Early data from combination studies
      of ibrutinib with anti-CD20 monoclonal antibodies have shown more rapid responses
      compared to those seen with ibrutinib monotherapy. Current data strongly support
      continued clinical evaluation of ibrutinib in B-cell malignancies. 

PMID- 25387839
TI  - Adjunctive steroid therapy for managing pulmonary tuberculosis.
AB  - BACKGROUND: Tuberculosis causes approximately 8.6 million disease episodes and
      1.3 million deaths worldwide per year. Although curable with standardized
      treatment, outcomes for some forms of tuberculosis are improved with adjunctive
      corticosteroid therapy. Whether corticosteroid therapy would be beneficial in
      treating people with pulmonary tuberculosis is unclear. OBJECTIVES: To evaluate
      whether adjunctive corticosteroid therapy reduces mortality, accelerates clinical
      recovery or accelerates microbiological recovery in people with pulmonary
      tuberculosis. SEARCH METHODS: We identified studies indexed from 1966 up to May
      2014 by searching: Cochrane Infectious Diseases Group's trials register, Cochrane
      Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS using
      comparative search terms. We handsearched reference lists of all identified
      studies and previous reviews and contacted relevant researchers, organizations
      and companies to identify grey literature. SELECTION CRITERIA: Randomized
      controlled trials and quasi-randomized control trials of recognized antimicrobial
      combination regimens and corticosteroid therapy of any dose or duration compared
      with either no corticosteroid therapy or placebo in people with pulmonary
      tuberculosis were included. DATA COLLECTION AND ANALYSIS: At least two
      investigators independently assessed trial quality and collected data using pre
      specified data extraction forms. Findings were reported as narrative or within
      tables. If appropriate, Mantel-Haenszel meta-analyses models were used to
      calculate risk ratios. MAIN RESULTS: We identified 18 trials, including 3816
      participants, that met inclusion criteria. When compared to taking placebo or no
      steroid, corticosteroid use was not shown to to reduce all-cause mortality, or
      result in higher sputum conversion at 2 months or at 6 months (mortality: RR
      0.77, 95%CI 0.51 to 1.15, 3815 participants, 18 studies, low quality evidence;
      sputum conversion at 2 months RR 1.03, 95%CI 0.97 to 1.09, 2750 participants, 12
      studies; at 6 months; RR1.01, 95%CI 1.01, 95%CI 0.98 to 1.04, 2150 participants,
      9 studies, both low quality evidence). However, corticosteroid use was found to
      increase weight gain (data not pooled, eight trials, 1203 participants, low
      quality evidence), decrease length of hospital stay (data not pooled, three
      trials, participants 379, very low quality of evidence) and increase clinical
      improvement within one month (RR 1.16, 95% CI 1.09 to 1.24; five trials, 497
      participants, low quality evidence). AUTHORS' CONCLUSIONS: It is unlikely that
      adjunctive corticosteroid treatment provides major benefits for people with
      pulmonary tuberculosis. Short term clinical benefits found did not appear to be
      maintained in the long term. However, evidence available to date is of low
      quality. In order to evaluate whether adjunctive corticosteroids reduce
      mortality, or accelerate clinical or microbiological recovery in people with
      pulmonary tuberculosis further large randomized control trials sufficiently
      powered to detect changes in such outcomes are needed.

PMID- 25387840
TI  - Should pediatric tympanomastoidectomy and cochlear implantation routinely Be
      performed as outpatient surgery?

PMID- 25387841
TI  - Engineering the cell-semiconductor interface: a materials modification approach
      using II-VI and III-V semiconductor materials.
AB  - Developing functional biomedical devices based on semiconductor materials
      requires an understanding of interactions taking place at the material-biosystem
      interface. Cell behavior is dependent on the local physicochemical environment.
      While standard routes of material preparation involve chemical functionalization
      of the active surface, this review emphasizes both biocompatibility of unmodified
      surfaces as well as use of topographic features in manipulating cell-material
      interactions. Initially, the review discusses experiments involving unmodified II
      VI and III-V semiconductors - a starting point for assessing cytotoxicity and
      biocompatibility - followed by specific surface modification, including the
      generation of submicron roughness or the potential effect of quantum dot
      structures. Finally, the discussion turns to more recent work in coupling
      topography and specific chemistry, enhancing the tunability of the cell
      semiconductor interface. With this broadened materials approach, researchers'
      ability to tune the interactions between semiconductors and biological
      environments continues to improve, reaching new heights in device function. 

PMID- 25387842
TI  - Rare case of Langerhans cell sarcoma with cutaneous manifestation arising on the
      inguinal region.

PMID- 25387843
TI  - Evaluation of macular thickness changes after intracameral vancomycin in cataract
      surgery.
AB  - The purpose of this study was to determine the effect of intracameral injection
      of vancomycin at the end of routine cataract surgery on macular thickness using
      spectral domain optical coherence tomography. This prospective comparative case
      series included sixty eyes of 42 patients undergoing cataract surgery. Eyes were
      divided into two groups: 30 eyes (Group 1) received an intracameral injection of
      vancomycin (1 mg/0.1 ml) at the end of surgery, and 30 eyes (Group 2) received an
      intracameral injection of cefuroxime (1 mg/0.1 ml). Visual acuity, average
      macular thickness, and retinal thickness in 9 Early Treatment Diabetic
      Retinopathy Study (ETDRS) sectors were measured at baseline, and 1 week, 1 month,
      and 3 months after surgery. There were no differences in age, gender, visual
      acuity, and preoperative macular thickness between groups. In Group 1, average
      macular thickness significantly increased 1 month after surgery compared with
      baseline (P = 0.000) and then stabilized. Retinal thickness significantly
      increased in most of the ETDRS map sectors at 1-month follow-up. In Group 2,
      there was a significant increase in average macular thickness 1 month after
      surgery compared with baseline (P = 0.037). Likewise, retinal thickness increased
      in most of the ETDRS subfields at 1 month. Postoperative retinal thickness values
      and best-corrected visual acuity were similar in both groups 1 week, 1 month, and
      3 months after surgery. Intracameral injection of vancomycin at the end of
      cataract surgery showed comparable effects to cefuroxime in terms of macular
      thickness changes and visual acuity.

PMID- 25387844
TI  - Isolation and genetic characterization of an Actinobacillus pleuropneumoniae
      serovar K12:O3 strain.
AB  - An atypical Actinobacillus pleuropneumoniae serovar 12 strain, termed QAS106, was
      isolated from a clinical case of porcine pleuropneumonia in Japan. An
      immunodiffusion (ID) test identified the strain as serovar 12. However, the ID
      test also demonstrated that strain QAS106 shared antigenic determinants with both
      the serovar 3 and 15 reference strains. Strain QAS106 was positive in the
      capsular serovar 12-specific polymerase chain reaction (PCR) assay, while the PCR
      toxin gene profiling and omlA PCR typing assays indicated that strain QAS106 was
      similar to serovar 3. The nucleotide sequence of the 16S ribosomal DNA (rDNA) of
      strain QAS106 was identical with that of serovars 3 and 12, but it showed 99.7%
      identity with that of serovar 15. Nucleotide sequence analysis revealed that
      genes involved in biosynthesis of the capsular polysaccharide (CPS) of strain
      QAS106 were identical to those of serovar 12 at the amino acid level. On the
      other hand, strain QAS106 would express putative proteins involved in the
      biosynthesis of lipopolysaccharide (LPS) O-polysaccharide (O-PS), the amino acid
      sequences of which were identical or nearly identical to those of serovars 3 and
      15. In conclusion, strain QAS106 should be recognized as K12:O3, even though
      typical serovar 12 strains are K12:O12. The emergence of an atypical A.
      pleuropneumoniae serovar 12 strain expressing a rare combination of CPS and O-PS
      antigens would hamper precise serodiagnosis by the use of either CPS- or LPS
      based serodiagnostic methodology alone. 

PMID- 25387845
TI  - Sequence-characterized amplified regions that differentiate New World screwworms
      from other potential wound-inhabiting flies.
AB  - New World screwworms, Cochliomyia hominivorax (Coquerel, 1858), were once
      devastating pests of warm-blooded animals in the United States before they were
      successfully eradicated using the sterile insect technique. Guarding against the
      introduction of screwworms to North America or any other screwworm-free area
      relies on rapid, reliable identification of suspected cases. In the current
      study, the DNA from excised markers generated by randomly amplified polymorphic
      DNA polymerase chain reaction was used as the basis to generate 2 species
      specific sequence-characterized amplified region molecular markers. Resulting
      primer pairs, named CR92A1 and J1A2 (each with forward and reverse components),
      produced amplicons of 852 and 848 base pairs, respectively. The 2 primer pairs
      successfully discriminated between C. hominivorax, Cochliomyia macellaria
      (Fabricius, 1775), 8 other species of blowflies, 3 noncalliphorid dipterans, and
      1 nondipteran outlier. These primers may become important tools for veterinary
      laboratories and the screwworm eradication and exclusion program for rapid
      identification or verification of suspicious larval samples in presumed
      outbreaks. 

PMID- 25387846
TI  - Accounting for nanometer-thick adventitious carbon contamination in X-ray
      absorption spectra of carbon-based materials.
AB  - Near-edge X-ray absorption fine structure (NEXAFS) spectroscopy is a powerful
      technique for characterizing the composition and bonding state of nanoscale
      materials and the top few nanometers of bulk and thin film specimens. When
      coupled with imaging methods like photoemission electron microscopy, it enables
      chemical imaging of materials with nanometer-scale lateral spatial resolution.
      However, analysis of NEXAFS spectra is often performed under the assumption of
      structural and compositional homogeneity within the nanometer-scale depth probed
      by this technique. This assumption can introduce large errors when analyzing the
      vast majority of solid surfaces due to the presence of complex surface and near
      surface structures such as oxides and contamination layers. An analytical
      methodology is presented for removing the contribution of these nanoscale
      overlayers from NEXAFS spectra of two-layered systems to provide a corrected
      photoabsorption spectrum of the substrate. This method relies on the subtraction
      of the NEXAFS spectrum of the overlayer adsorbed on a reference surface from the
      spectrum of the two-layer system under investigation, where the thickness of the
      overlayer is independently determined by X-ray photoelectron spectroscopy (XPS).
      This approach is applied to NEXAFS data acquired for one of the most challenging
      cases: air-exposed hard carbon-based materials with adventitious carbon
      contamination from ambient exposure. The contribution of the adventitious carbon
      was removed from the as-acquired spectra of ultrananocrystalline diamond (UNCD)
      and hydrogenated amorphous carbon (a-C:H) to determine the intrinsic
      photoabsorption NEXAFS spectra of these materials. The method alters the
      calculated fraction of sp(2)-hybridized carbon from 5 to 20% and reveals that the
      adventitious contamination can be described as a layer containing carbon and
      oxygen ([O]/[C] = 0.11 +/- 0.02) with a thickness of 0.6 +/- 0.2 nm and a
      fraction of sp(2)-bonded carbon of 0.19 +/- 0.03. This method can be generally
      applied to the characterization of surfaces and interfaces in several research
      fields and technological applications. 

PMID- 25387847
TI  - Lack of evidence of the interaction of the Abeta peptide with the Wnt signaling
      cascade in Drosophila models of Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the leading form of dementia worldwide.
      The Abeta-peptide is believed to be the major pathogenic compound of the disease.
      Since several years it is hypothesized that Abeta impacts the Wnt signaling
      cascade and therefore activation of this signaling pathway is proposed to rescue
      the neurotoxic effect of Abeta. FINDINGS: Expression of the human Abeta42 in the
      Drosophila nervous system leads to a drastically shortened life span. We found
      that the action of Abeta42 specifically in the glutamatergic motoneurons is
      responsible for the reduced survival. However, we find that the morphology of the
      glutamatergic larval neuromuscular junctions, which are widely used as the model
      for mammalian central nervous system synapses, is not affected by Abeta42
      expression. We furthermore demonstrate that genetic activation of the Wnt signal
      transduction pathway in the nervous system is not able to rescue the shortened
      life span or a rough eye phenotype in Drosophila. CONCLUSIONS: Our data confirm
      that the life span is a useful readout of Abeta42 induced neurotoxicity in
      Drosophila; the neuromuscular junction seems however not to be an appropriate
      model to study AD in flies. Additionally, our results challenge the hypothesis
      that Wnt signaling might be implicated in Abeta42 toxicity and might serve as a
      drug target against AD.

PMID- 25387848
TI  - Doctors and baldness: a five thousand year old challenge.
AB  - The history of trichology follows a thread that continually intersects with that
      of the history of medicine in general. Even Hippocrates believed that the
      approach to baldness should be of a medical nature. This confrontation between
      doctors and hair loss, which has lasted for five thousand years, begins with the
      invocations of the head physicians in the Egyptian era and ends with the recent
      institution of postgraduate Master's degrees at Faculties of Medicine and
      Surgery. The biggest names in medicine concerned themselves with trichology
      beginning with Hippocrates, who dealt with the topic in his most famous work: the
      Aphorisms. Even the most celebrated doctors of the Roman era, such as Galen and
      Pliny the Elder, did not disdain considering hair loss, leaving important
      scientific contributions before passing on the baton to their distinguished
      colleagues of the Byzantine Empire. The narrative then flows through the most
      prestigious institutions of the Middle Ages, such as the Salerno School of
      Medicine and the Siena Accademia del Fisiocritici where, at the end of the 1600s,
      the distinguished anatomical describer Marcello Malpighi also taught trichology,
      and left his contribution to "Hair Science" with a fine description of the hair
      follicle in the pages of his Opera Posthuma. At the turn of the late Middle Ages
      and the early modern era, barbers formed the primordial nucleus of surgery and at
      the same time became the ones to concern themselves with hair loss. In the 1800s,
      several doctors published the first texts dealing with the anatomy and physiology
      of the hair and taking into account the principal forms of alopecia, but at the
      therapeutic level did not yet propose anything scientifically valid. Until a few
      decades ago trichology still lent itself to various commercial speculations. It
      was not until the twentieth century that the pathogenetic mechanisms of baldness
      were clarified in a scientific manner. With this knowledge, the pharmaceutical
      industry has been able, then, to develop the necessary drugs, and doctors have
      become willing and able to reappropriate treatments to counteract conditions that
      lead to hair loss.

PMID- 25387849
TI  - Hidradenoma papilliferum: diagnostic challenge.

PMID- 25387850
TI  - Ferromagnetism of Fe3Sn and alloys.
AB  - Hexagonal Fe(3)Sn has many of the desirable properties for a new permanent magnet
      phase with a Curie temperature of 725 K, a saturation moment of 1.18 MA/m. and
      anisotropy energy, K1 of 1.8 MJ/m(3). However, contrary to earlier experimental
      reports, we found both experimentally and theoretically that the easy magnetic
      axis lies in the hexagonal plane, which is undesirable for a permanent magnet
      material. One possibility for changing the easy axis direction is through
      alloying. We used first principles calculations to investigate the effect of
      elemental substitutions. The calculations showed that substitution on the Sn site
      has the potential to switch the easy axis direction. However, transition metal
      substitutions with Co or Mn do not have this effect. We attempted synthesis of a
      number of these alloys and found results in accord with the theoretical
      predictions for those that were formed. However, the alloys that could be readily
      made all showed an in-plane easy axis. The electronic structure of Fe(3)Sn is
      reported, as are some are magnetic and structural properties for the Fe(3)Sn(2),
      and Fe(5)Sn(3) compounds, which could be prepared as mm-sized single crystals.

PMID- 25387851
TI  - High numbers of macrophages, especially M2-like (CD163-positive), correlate with
      hyaluronan accumulation and poor outcome in breast cancer.
AB  - AIMS: High amounts of tumour-associated macrophages (TAMs) and hyaluronan (HA)
      correlate with tumour aggressiveness in breast cancer, but the relationship
      between these parameters is unclear. The aim of this study was to assay the
      numbers of TAMs in 278 human breast cancer cases, and their correlations with HA
      related factors, clinical variables, and outcome. METHODS AND RESULTS: The
      immunoreactivities for CD163 and CD68 were considered as indicators for M2-like
      and all TAMs, respectively. The numbers of TAMs were counted in at least four hot
      spots, and averaged to represent the numbers of TAMs in each section. In the
      statistical analyses, the numbers were graded as either low or high according to
      the median. High numbers of TAMs correlated with a high tumour HA content, HA
      synthases, CD44 positivity, and poor outcome. The number of CD163-positive cells
      represented a strong independent prognostic factor. There was also a significant
      correlation between obesity and a high number of CD163-positive cells.
      CONCLUSIONS: Concurrent increases in TAMs and HA in breast cancer indicate that
      the accumulation of HA facilitates macrophage infiltration and inflammatory
      responses during human breast cancer progression.

PMID- 25387852
TI  - Are general surgery residents adequately prepared for hepatopancreatobiliary
      fellowships? A questionnaire-based study.
AB  - BACKGROUND: The present study was conducted to assess the preparedness of
      hepatopancreatobiliary (HPB) fellows upon entering fellowship, identify
      challenges encountered by HPB fellows during the initial part of their HPB
      training, and identify potential solutions to these challenges that can be
      applied during residency training. METHODS: A questionnaire was distributed to
      all HPB fellows in accredited HPB fellowship programmes in two consecutive
      academic years (n = 42). Reponses were then analysed. RESULTS: A total of 19
      (45%) fellows responded. Prior to their fellowship, 10 (53%) were in surgical
      residency and the rest were in other surgical fellowships or surgical practice.
      Thirteen (68%) were graduates of university-based residency programmes. All
      fellows felt comfortable in performing basic laparoscopic procedures
      independently at the completion of residency and less comfortable in performing
      advanced laparoscopy. Eight (42%) fellows cited a combination of inadequate case
      volume and lack of autonomy during residency as the reasons for this lack of
      comfort. Thirteen (68%) identified inadequate preoperative workup and management
      as their biggest fear upon entering practice after general surgery training. A
      total of 17 (89%) fellows felt they were adequately prepared to enter HPB
      fellowship. Extra rotations in transplant, vascular or minimally invasive surgery
      were believed to be most helpful in preparing general surgery residents pursing
      HPB fellowships. CONCLUSIONS: Overall, HPB fellows felt themselves to be
      adequately prepared for fellowship. Advanced laparoscopic procedures and the
      perioperative management of complex patients are two of the challenges facing HPB
      fellows. General surgery residents who plan to pursue an HPB fellowship may
      benefit from spending extra rotations on certain subspecialties. Focus on
      perioperative workup and management should be an integral part of residency and
      fellowship training.

PMID- 25387853
TI  - Dietary deficiencies of unsaturated fatty acids and starch cause atopic
      dermatitis-like pruritus in hairless mice.
AB  - Hairless mice fed with a special diet (named HR-AD) show atopic dermatitis (AD)
      like pruritic skin inflammation that is almost completely resolved with the
      supplementation of an unsaturated fatty acid (UFA), the linoleic acid (LA). This
      suggests that the dietary deficiency of LA is the key cause of this dermatitis.
      However, because there is no appropriate control diet for HR-AD, the involvement
      of other dietary ingredients cannot be ruled out. Furthermore, it has not yet
      been tested whether only UFA deficiency can cause such AD-like pruritus. In this
      study, using semi-purified custom diets, we attempted to reproduce this syndrome.
      Four-week-old hairless mice were maintained on a widely used standard diet
      American Institute of Nutrition-76A (AIN-76A), its modifications, or HR-AD.
      Several modifications of fat and carbohydrate components revealed that dietary
      deficiency of both UFAs and cornstarch was required to induce severe skin barrier
      dysfunction as typically occurred in HR-AD-fed mice. An UFA- and cornstarch
      deficient diet caused severe AD-like pruritus comparable to HR-AD, despite weak
      Th2 immune responses and absence of immunoglobulin E production. On the other
      hand, a diet lacking UFAs but containing cornstarch significantly alleviated the
      development of pruritic dermatitis. Furthermore, the supplementation of wheat
      starch similarly improved skin barrier function. In conclusion, this study showed
      that a lack of certain starches might also be the cause of diet-induced AD. Our
      findings could help to reproduce the diet-induced AD itch model and also provide
      evidence that certain starches can have protective and ameliorative effects on AD
      like pruritus. 

PMID- 25387854
TI  - Postcopulatory inbreeding avoidance in guppies.
AB  - In many species, the negative fitness effects of inbreeding have facilitated the
      evolution of a wide range of inbreeding avoidance mechanisms. Although avoidance
      mechanisms operating prior to mating are well documented, evidence for
      postcopulatory mechanisms of inbreeding avoidance remain scarce. Here, we examine
      the potential for paternity biases to favour unrelated males when their sperm
      compete for fertilizations though postcopulatory inbreeding avoidance mechanisms
      in the guppy, Poecilia reticulata. To test this possibility, we used a series of
      artificial inseminations to deliver an equal number of sperm from a related
      (either full sibling or half sibling) and unrelated male to a female while
      statistically controlling for differences in sperm quality between rival
      ejaculates. In this way, we were able to focus exclusively on postcopulatory
      mechanisms of inbreeding avoidance and account for differences in sperm
      competitiveness between rival males. Under these carefully controlled conditions,
      we report a significant bias in paternity towards unrelated males, although this
      effect was only apparent when the related male was a full sibling. We also show
      that sperm competition generally favours males with highly viable sperm and thus
      that some variance in sperm competitiveness can be attributed to difference in
      sperm quality. Our findings for postcopulatory inbreeding avoidance are
      consistent with prior work on guppies, revealing that sperm competition success
      declines linearly with the level of relatedness, but also that such effects are
      only apparent at relatedness levels of full siblings or higher. These findings
      reveal that postcopulatory processes alone can facilitate inbreeding avoidance. 

PMID- 25387855
TI  - Insulin degludec improves long-term glycaemic control similarly to insulin
      glargine but with fewer hypoglycaemic episodes in patients with advanced type 2
      diabetes on basal-bolus insulin therapy.
AB  - The aim of the present study was to compare the long-term safety and efficacy of
      insulin degludec with those of insulin glargine in patients with advanced type 2
      diabetes (T2D) over 78 weeks (the 52-week main trial and a 26-week extension).
      Patients were randomized to once-daily insulin degludec or insulin glargine, with
      mealtime insulin aspart +/- metformin +/- pioglitazone, and titrated to pre
      breakfast plasma glucose values of 3.9-4.9 mmol/l (70-88 mg/dl). After 78 weeks,
      the overall rate of hypoglycaemia was 24% lower (p = 0.011) and the rate of
      nocturnal hypoglycaemia was 31% lower (p = 0.016) with insulin degludec in the
      extension trial set, while both groups of patients achieved similar glycaemic
      control. Rates of adverse events and total insulin doses were similar for both
      groups in the safety analysis set. During 18 months of treatment, insulin
      degludec + mealtime insulin aspart +/- oral antidiabetic drugs in patients with
      T2D improves glycaemic control similarly, but confers lower risks of overall and
      nocturnal hypoglycaemia than with insulin glargine treatment. 

PMID- 25387857
TI  - Standardized assessment of seizures in patients with juvenile neuronal ceroid
      lipofuscinosis.
AB  - AIM: To evaluate seizure phenomenology, treatment, and course in individuals with
      juvenile neuronal ceroid lipofuscinosis (JNCL). METHOD: Data from an ongoing
      natural history study of JNCL were analyzed using cross-sectional and
      longitudinal methods. Seizures were evaluated with the Unified Batten Disease
      Rating Scale, a disease-specific quantitative assessment tool. RESULTS: Eighty
      six children (44 males, 42 females) with JNCL were assessed at an average of
      three annual visits (range 1-11). Eighty-six percent (n=74) experienced at least
      one seizure, most commonly generalized tonic-clonic, with mean age at onset of 9
      years 7 months (SD 2y 10mo). Seizures were infrequent, typically occurring less
      often than once every 3 months, and were managed with one to two medications for
      most participants. Valproate (49%, n=36) and levetiracetam (41%, n=30) were the
      most commonly used seizure medications. Myoclonic seizures occurred infrequently
      (16%, n=14). Seizure severity did not vary by sex or genotype. Seizures showed
      mild worsening with increasing age. INTERPRETATION: The neuronal ceroid
      lipofuscinoses (NCLs) represent a group of disorders unified by neurodegeneration
      and symptoms of blindness, seizures, motor impairment, and dementia. While NCLs
      are considered in the differential diagnosis of progressive myoclonus epilepsy,
      we show that myoclonic seizures are infrequent in JNCL. This highlights the NCLs
      as consisting of genetically distinct disorders with differing natural history.

PMID- 25387858
TI  - Behavior of in situ human native adipose tissue CD34+ stromal/progenitor cells
      during different stages of repair. Tissue-resident CD34+ stromal cells as a
      source of myofibroblasts.
AB  - CD34+ adipose stromal cells are scattered in the adipose tissue and found in the
      CD34+ population of the stromal vascular fraction (SVF). This fraction includes
      adipose-derived stromal/stem/progenitor cells (ASCs), which have attracted
      considerable attention and show great promise for the future of regenerative
      medicine. Studies in this field have been undertaken mainly in vitro. In this
      work, however, we assessed the characteristics of human adipose tissue-resident
      CD34+ stromal cells in normal conditions and when activated in vivo during
      inflammatory/repair processes at different stages of evolution. In normal adipose
      tissue, these cells showed a characteristic location (peri/paravascular and
      between adipocytes), a fusiform or stellate morphology, long and moniliform
      processes, and scarce organelles. During inflammatory/repair stages, native CD34+
      stromal cells increased in size, proliferated, developed numerous organelles of
      synthesis, lost CD34 expression, and differentiated into myofibroblasts (alphaSMA
      expression and typical ultrastructure). In double-stained sections, cells
      expressing both CD34 and alphaSMA were observed. CD34 expression correlated
      positively with a high proliferative capacity (Ki-67 expression). Conversely,
      CD34 expression was lost with successive mitoses and with increased numbers of
      macrophages in the granulation tissue. CD34+ stromal cell behavior varied
      depending on proximity to (with myofibroblast differentiation) or remoteness from
      (with activated plump cells conserving CD34 expression) injury. In conclusion,
      our observations point to human adipose tissue-resident CD34+ stromal cells as an
      important source of myofibroblasts during inflammatory/repair processes.
      Moreover, stromal cell activation may occur with or without alphaSMA expression
      (with or without myofibroblast transformation) and with loss or persistence of
      CD34 expression, respectively.

PMID- 25387859
TI  - Preference for using posts to restore endodontically treated teeth: findings from
      a survey with dentists.
AB  - The aim of this study was to evaluate if clinical experience, whether in relation
      to length of practice time and/or level of specialization influences the
      dentist's preference for using posts to restore endodontically treated teeth. A
      cross sectional study was carried out using a questionnaire with dentists (n =
      276) in Pelotas, southern Brazil. Data were collected regarding clinical
      experience, post-graduate training, and variables related to restorations
      (posts/cements and use of rubber dam) for endodontically treated teeth. The data
      were submitted to a descriptive analysis and associations were tested. The
      response rate was 68%. Cast metal posts (24.53%), glass fiber posts (20.75%) and
      resin cement (66.67%) were the most commonly selected materials. In relation to
      rubber dams, 93.05% of the dentists were found not use them to lute posts. There
      was a significant association between the level of training of post-graduate
      dentists and the type of post used (p = 0.027), in that dentists without post
      graduate training used cast metal posts more frequently, whereas dentists with
      post-graduate training reported glass fiber posts as their first choice. The
      results of the study showed that dentists preferred cast metal posts, glass fiber
      posts and resin cement. Continuing education influenced the decision of the
      dentists on their choice of dental posts. 

PMID- 25387860
TI  - Assessment of apically extruded debris and irrigant produced by different nickel
      titanium instrument systems.
AB  - The aim of this study was to evaluate the preparation time and the amounts of
      apically extruded debris and irrigant using different nickel-titanium
      instrumentation systems. Forty-five extracted single-rooted mandibular premolar
      teeth were selected and divided into three groups. The root canals were
      instrumented according to the manufacturers' instructions, using a reciprocating
      single-file system, a single-file rotary system and a multiple-file rotary
      system. Bidistilled water was used as the irrigant solution. The apically
      extruded debris and irrigant were collected into preweighed Eppendorf tubes. The
      amounts of extruded debris and irrigant were assessed with a precision micro
      balance. The Eppendorf tubes were incubated at 37 degrees C for 15 days. After
      the incubation period, they were weighed again to assess the debris extrusion.
      The time required to prepare the canals was also recorded. The results were
      statistically analyzed using MANOVA and Bonferroni's adjustment. Considering the
      apically extruded debris and irrigant, there were no statistically significant
      differences among the groups (p > 0.05). The Reciproc group produced the highest
      debris (0.000632 +/- 0.000162 gr) and irrigant (0.844587 +/- 0.437814 ml)
      extrusion values. While the least extruded debris was observed with OneShape
      (0,000431 +/- 0,000171 gr), the least extruded irrigant was observed with
      ProTaper system (0.564147 +/- 0.370596 ml). Instrumentation was faster using the
      Reciproc than the other two instruments (70.27 +/- 13.38 s) (p < 0.05). All of
      the instrumentation systems used in this study produced apical debris and
      irrigant extrusion. The reciprocating single-file system tended to produce more
      debris and irrigant extrusion, compared with the rotary systems. Considering the
      preparation time, the single-file systems appeared to be advantageous due to
      their working time. 

PMID- 25387861
TI  - Extracorporeal CO2 removal as bridge to lung transplantation in life-threatening
      hypercapnia.
AB  - In patients awaiting lung transplantation (LTX), adequate gas exchange may not be
      sufficiently achieved by mechanical ventilation alone if acute respiratory
      decompensation arises. We report on 20 patients with life-threatening hypercapnia
      who received extracorporeal CO2 removal (ECCO2-R) by means of the interventional
      lung assist (ILA(r), Novalung) as bridge to LTX. The most common underlying
      diagnoses were bronchiolitis obliterans syndrome, cystic fibrosis, and idiopathic
      pulmonary fibrosis, respectively. The type of ILA was pumpless arteriovenous or
      pump-driven venovenous (ILA activve(r), Novalung) in 10 patients each. ILA
      bridging was initiated in 15 invasively ventilated and five noninvasively
      ventilated patients, of whom one had to be intubated prior to LTX. Hypercapnia
      and acidosis were effectively corrected in all patients within the first 12 h of
      ILA therapy: PaCO2 declined from 109 (70-146) to 57 (45-64) mmHg, P < 0.0001; pH
      increased from 7.20 (7.06-7.28) to 7.39 (7.35-7.49), P < 0.0001. Four patients
      were switched to extracorporeal membrane oxygenation due to progressive hypoxia
      or circulatory failure. Nineteen patients (95%) were successfully transplanted.
      Hospital and 1-year survival was 75 and 72%, respectively. Bridging to LTX with
      ECCO2-R delivered by arteriovenous pumpless or venovenous pump-driven ILA is
      feasible and associated with high transplantation and survival rates. 

PMID- 25387862
TI  - Genetic diversity and evolution of two capsid protein genes of citrus tristeza
      virus isolates from China.
AB  - The genetic diversity and population structure of citrus tristeza virus (CTV)
      isolates from China were investigated based on partial sequences spanning the C
      terminal end of p61 and the complete sequences of the CPm and CP genes.
      Phylogenetic analysis revealed five known groups (RB, T30, T36, HA and VT) and
      one new group (VI) consisting of only Chinese CTV isolates. Incongruent
      phylogenetic trees coupled with recombination analysis suggested several
      recombination events in the CPm gene. Positive selection was detected at codon 9
      of CPm and codons 31, 41 and 68 of CP. The widespread CTV subpopulation AT-1
      found in China has a unique amino acid insertion at the C-terminus of p61, which
      could increase CTV population complexity with implications for the evolutionary
      history of the virus. Our results suggest relevant roles for gene flow, purifying
      selection and recombination in shaping the CTV population in China.

PMID- 25387856
TI  - Prediction of individual response to anticancer therapy: historical and future
      perspectives.
AB  - Since the introduction of chemotherapy for cancer treatment in the early 20th
      century considerable efforts have been made to maximize drug efficiency and at
      the same time minimize side effects. As there is a great interpatient variability
      in response to chemotherapy, the development of predictive biomarkers is an
      ambitious aim for the rapidly growing research area of personalized molecular
      medicine. The individual prediction of response will improve treatment and thus
      increase survival and life quality of patients. In the past, cell cultures were
      used as in vitro models to predict in vivo response to chemotherapy. Several in
      vitro chemosensitivity assays served as tools to measure miscellaneous endpoints
      such as DNA damage, apoptosis and cytotoxicity or growth inhibition. Twenty years
      ago, the development of high-throughput technologies, e.g. cDNA microarrays
      enabled a more detailed analysis of drug responses. Thousands of genes were
      screened and expression levels were correlated to drug responses. In addition,
      mutation analysis became more and more important for the prediction of
      therapeutic success. Today, as research enters the area of -omics technologies,
      identification of signaling pathways is a tool to understand molecular mechanism
      underlying drug resistance. Combining new tissue models, e.g. 3D organoid
      cultures with modern technologies for biomarker discovery will offer new
      opportunities to identify new drug targets and in parallel predict individual
      responses to anticancer therapy. In this review, we present different currently
      used chemosensitivity assays including 2D and 3D cell culture models and several 
      omics approaches for the discovery of predictive biomarkers. Furthermore, we
      discuss the potential of these assays and biomarkers to predict the clinical
      outcome of individual patients and future perspectives. 

PMID- 25387863
TI  - Reply: To PMID 24817269.

PMID- 25387864
TI  - Detection and isolation of the alpha-proteobacterium Asaia in Culex mosquitoes.
AB  - Investigations of microbiota within mosquitoes continue to widen the spectrum of
      possible symbiont-based applications against vector-borne diseases. In this
      context, alpha-proteobacteria of the genus Asaia (Rhodospirillales:
      Acetobacteraceae) are emerging as possible endosymbiotic candidates, particularly
      in paratransgenic approaches aimed at interrupting pathogen transmission.
      Previous studies have shown that Asaia spp. distribution among Anopheles gambiae
      and Anopheles stephensi (Diptera: Culicidae) mosquitoes displayed positive rates
      of infection in isolated midguts, salivary glands and reproductive tissues.
      Similarly, Asaia has been detected in Aedes albopictus (Stegomyia albopicta) and
      Aedes aegypti (Stegomyia aegypti) (Diptera: Culicidae) populations. Within the
      Culex pipiens complex (Diptera: Culicidae), Asaia infection is still largely
      unexplored. Here, we summarize a preliminary survey of laboratory-reared Cx.
      pipiens complex and field-collected Culex quinquefasciatus for the presence of
      Asaia spp., and present the first identification of Asaia in some of the members
      of the Cx. pipiens complex and the first description in West African populations
      of Cx. quinquefasciatus.

PMID- 25387866
TI  - Phase 1/2 study of nilotinib prophylaxis after allogeneic stem cell
      transplantation in patients with advanced chronic myeloid leukemia or
      Philadelphia chromosome-positive acute lymphoblastic leukemia.
AB  - BACKGROUND: Allogeneic stem cell transplantation (SCT) remains the standard
      treatment for advanced chronic myeloid leukemia (CML) and Philadelphia chromosome
      positive acute lymphoblastic leukemia (Ph(+) ALL). Relapsed disease is the major
      cause of treatment failure, especially when SCT is given in the setting of
      advanced disease. Tyrosine kinase inhibitors can be given after transplantation
      prophylactically or after the detection of minimal residual disease (MRD) to
      reduce the relapse risk. METHODS: Posttransplant nilotinib was started after the
      achievement of sustained engraftment and the resolution of transplant-related
      toxicities. Nilotinib was continued until progression or unacceptable toxicity.
      RESULTS: Twenty-two patients with advanced CML (n = 15) or Ph(+) ALL (n = 7)
      underwent SCT with human leukocyte antigen-matched siblings (n = 11), unrelated
      donors (n = 7), or alternative donors (n = 4). Sixteen patients were given
      prophylactic nilotinib maintenance, which was started at a median of 38 days
      after transplantation. Six patients stopped the treatment because of toxicities
      (mostly gastrointestinal and hepatic). After nilotinib maintenance, 11 patients
      achieved (n = 9) or maintained (n = 2) a complete molecular response (CMR), and
      only 1 of them later relapsed. Four of the 5 patients not achieving CMR relapsed.
      At a median follow-up of 46 months, 9 patients were alive, and 13 had died. The 2
      year overall and progression-free survival rates were 55% (95% confidence
      interval [CI], 34%-75%) and 45% (95% CI, 25%-66%), respectively. Among the 16
      nilotinib recipients, the rates were 69% (95% CI, 46%-92%) and 56% (95% CI, 32%
      81%), respectively. The 2-year nonrelapse mortality and relapse rates for all
      patients were 32% (95% CI, 17%-58%) and 23% (95% CI, 11%-49%), respectively.
      CONCLUSIONS: Nilotinib is relatively safe and effective prophylactic therapy for
      the prevention of relapse after SCT. It may control MRD and convert patients to
      CMR, which is associated with prolonged survival. These observations merit
      further study in larger scale studies.

PMID- 25387868
TI  - Volatiles in raw and cooked meat from lambs fed olive cake and linseed.
AB  - This study was conducted to determine the effects of feeding olive cake and
      linseed to lambs on the volatile organic compounds (VOCs) in raw and cooked meat.
      Four groups of eight male Appenninica lambs each were fed: conventional cereal
      based concentrates (diet C), concentrates containing 20% on a dry matter (DM)
      basis of rolled linseed (diet L), concentrates containing 35% DM of stoned olive
      cake (diet OC), or concentrates containing both rolled linseed (10% DM) and
      stoned olive cake (17% DM; diet OCL). The longissimus dorsi muscle of each lamb
      was sampled at slaughter and was subjected to VOC profiling through the use of
      SPME-GC-MS. In the raw meat, the concentration of 3-methylpentanoic acid was
      higher in treatment C as compared with treatments L, OC and OCL (P<0.01).
      Moreover the level of nonanoic acid was greater in treatments C and OC than in
      treatment L (P<0.05). With respect to alcohols, in raw meat the amount of 2
      phenoxyethanol in treatment OCL was lower than in treatments C (P<0.01) and OC
      (P<0.05), while in cooked meat the amount of 1-pentanol was higher in treatment C
      than in treatment OC (P<0.05). Apart from these compounds, none of the lipid
      oxidation-derived volatiles was significantly affected by the dietary treatment.
      Therefore, the results suggest that the replacement of cereal concentrates with
      linseed and/or olive cake did not cause appreciable changes in the production of
      volatile organic compounds in lamb meat. 

PMID- 25387869
TI  - The challenges of science journalism: The perspectives of scientists, science
      communication advisors and journalists from New Zealand.
AB  - The news media play an important role in informing the public about scientific
      and technological developments. Some argue that restructuring and downsizing
      result in journalists coming under increased pressure to produce copy, leading
      them to use more public relations material to meet their deadlines. This article
      explores science journalism in the highly commercialised media market of New
      Zealand. Using semi-structured interviews with scientists, science communication
      advisors and journalists, the study finds communication advisors and scientists
      believe most media outlets, excluding public service media, report science
      poorly. Furthermore, restructuring and staff cuts have placed the journalists
      interviewed under increasing pressure. While smaller newspapers appear to be
      printing press releases verbatim, metropolitan newspaper journalists still
      exercise control over their use of such material. The results suggest these
      journalists will continue to resist increasing their use of public relations
      material for some time to come. 

PMID- 25387867
TI  - Genetic variations underlying self-reported physical functioning: a review.
AB  - PURPOSE: Genetic associations with self-reported physical functioning (SPF) are
      less well-studied than genetic associations with performance-measured physical
      functioning (PPF). We review the literature on the associations of genetic
      variations on SPF. We provide an overview of SPF assessment, genetic
      contributions to SPF including heritability, effects of genetic variations and
      mutations, and effects of interventions on the gene-SPF relationship. We also aim
      to provide directions for future research. METHODS: A computerized literature
      search using PubMed, Web of Science, and PsychInfo was conducted to select
      relevant literature published up to November 2013. Inclusion criteria were the
      use of an SPF questionnaire, original articles in English on human subjects,
      published in peer-reviewed journals and reporting significant associations
      between SPF and the genome. RESULTS: Nineteen articles were included. SPF was
      commonly assessed with the Short Form-36 questionnaire involving mainly
      convenience samples of either older persons or chronically ill. Heritability
      estimates were 10-30 %. Candidate genes associated with SPF could be ascribed to
      biological pathways associated with neurodegeneration, physiological systems
      regulation, or cell regulation. The APOE gene associated with neurodegeneration
      was most studied (n = 3). Three papers included both SPF and PPF assessments. No
      genome-wide association study on SPF has been conducted. CONCLUSIONS:
      Associations between SPF and the genome have been investigated in selected
      populations in a limited number of publications. Future research should consider
      increasing sample variation and incorporate both SPF and PPF assessments. Also,
      longitudinal studies should be conducted in order to elicit stronger conclusions
      regarding the genetic associations with SPF.

PMID- 25387870
TI  - The palaeontological exhibition: a venue for dialogue.
AB  - Understanding the dialogue between museums and their visitors enables museums to
      subsist, undergo transformations and become consolidated as socially valued
      cultural venues. The Museo de La Plata (Argentina) was created in the late
      nineteenth century as a natural history museum, and this study shows that
      currently the museum is valued socially as a venue for family leisure and
      education, at which people make sense to the objects exhibited through
      characteristics conferred upon them by both the institution and the visitor.
      Nevertheless, such dialogue is somehow affected by the museographic proposal and
      the public interpretation of the institutional narrative, which could be analysed
      within the frame of contextual learning. As a consequence, the evolutionary idea
      that the museum aims to communicate is distorted by the public. This article
      highlights the importance of considering the visitors' interpretations when
      planning museum exhibitions, a perspective that has been rather absent in the
      Argentinian museums. 

PMID- 25387865
TI  - Insights from human congenital disorders of intestinal lipid metabolism.
AB  - The intestine must challenge the profuse daily flux of dietary fat that serves as
      a vital source of energy and as an essential component of cell membranes. The fat
      absorption process takes place in a series of orderly and interrelated steps,
      including the uptake and translocation of lipolytic products from the brush
      border membrane to the endoplasmic reticulum, lipid esterification, Apo
      synthesis, and ultimately the packaging of lipid and Apo components into
      chylomicrons (CMs). Deciphering inherited disorders of intracellular CM
      elaboration afforded new insight into the key functions of crucial intracellular
      proteins, such as Apo B, microsomal TG transfer protein, and Sar1b GTPase, the
      defects of which lead to hypobetalipoproteinemia, abetalipoproteinemia, and CM
      retention disease, respectively. These "experiments of nature" are characterized
      by fat malabsorption, steatorrhea, failure to thrive, low plasma levels of TGs
      and cholesterol, and deficiency of liposoluble vitamins and essential FAs. After
      summarizing and discussing the functions and regulation of these proteins for
      reader's comprehension, the current review focuses on their specific roles in
      malabsorptions and dyslipidemia-related intestinal fat hyperabsorption while
      dissecting the spectrum of clinical manifestations and managements. The influence
      of newly discovered proteins (proprotein convertase subtilisin/kexin type 9 and
      angiopoietin-like 3 protein) on fat absorption has also been provided. Finally,
      it is stressed how the overexpression or polymorphism status of the critical
      intracellular proteins promotes dyslipidemia and cardiometabolic disorders. 

PMID- 25387871
TI  - Myiasis on squamous cell carcinoma of skin.
AB  - Advanced squamous cell carcinoma (SCC) is a challenge for treatment. It is also a
      risk factor for unintended infestation with diptera larvae (maggots) known as
      myiasis. We performed a retrospective investigation in our files from 2001 to
      2014 and identified three patients with SCC-associated myiasis (three men). In
      all three cases, Lucilia spp. were found. A literature review using PUBMED
      revealed another 12 cases of SCC-associated myiasis due to different species. It
      is not only a disease of older age, as two of the patients were in their 20s. The
      male to female ratio was 2 to 1. Wound myiasis and cavity myiasis were seen in
      half of the cases each. Pain, bleeding, and infection were possible symptoms due
      to infestation but not all patients reported complaints. Treatment aims to
      completely remove all maggots and to prevent secondary tissue damage with
      blindness due to eye ball destruction as one of the worst. 

PMID- 25387873
TI  - Selective detection of Al(3+) and citric acid with a fluorescent amphiphile.
AB  - An amphiphilic fluorescent dye with a disulfonated BODIPY head group and a
      heptadecyl side chain is described. In buffered aqueous solution, the amphiphile
      can form aggregates with a critical micelle concentration of ~20 MUM. The
      aggregation of the dye is associated with a strong quenching of its fluorescence.
      Al(3+) promotes aggregation, whereas other metal ions have a much smaller effect,
      in particular when histidine is added as masking agent. The Al(3+)-induced
      aggregation can be used to sense Al(3+) in the low micromolar concentration range
      with high selectivity. Furthermore, we demonstrate that a dye-Al(3+) mixture can
      be used as a sensing ensemble for the detection of citric acid. The assay allows
      quantifying the citric acid content of commercial beverages such as energy
      drinks. 

PMID- 25387872
TI  - Conserved ion and amino acid transporters identified as phosphorylcholine
      modified N-glycoproteins by metabolic labeling with propargylcholine in
      Caenorhabditis elegans cells.
AB  - Phosphorylcholine (PC) modification of proteins by pathogens has been implicated
      in mediating host-pathogen interactions. Parasitic nematodes synthesize PC
      modified biomolecules that can modulate the host's antibody and cytokine
      production to favor nematode survival, contributing to long-term infections. Only
      two nematode PC-modified proteins (PC-proteins) have been unequivocally
      identified, yet discovering the protein targets of PC modification will be
      paramount to understanding the role(s) that this epitope plays in nematode
      biology. A major hurdle in the field has been the lack of techniques for
      selective purification of PC-proteins. The nonparasitic nematode Caenorhabditis
      elegans expresses PC-modified N-linked glycans, offering an attractive model to
      study the biology of PC-modification. We developed a robust method to identify PC
      proteins by metabolic labeling of primary embryonic C. elegans cells with
      propargylcholine, an alkyne-modified choline analog. Cu(I)-catalyzed
      cycloaddition with biotin-azide enables streptavidin purification and subsequent
      high-throughput LC-MS identification of propargyl-labeled proteins. All proteins
      identified using stringent criteria are known or predicted to be membrane or
      secreted proteins, consistent with the model of a Golgi-resident, putative PC
      transferase. Of the 55 PC-N-glycosylation sites reported, 33 have been previously
      observed as N-glycosylation sites in high-throughput screens of C. elegans.
      Several identified PC-proteins are nematode-specific proteins, but 10 of the PC
      proteins are widely conserved ion transporters and amino acid transporters, while
      eight are conserved proteins involved in synaptic function. This finding suggests
      a functional role for PC-modification beyond immunomodulation. The approach
      presented in this study provides a method to identify PC-proteins in C. elegans
      and related nematodes. 

PMID- 25387874
TI  - Nuclear stability and transcriptional directionality separate functionally
      distinct RNA species.
AB  - Mammalian genomes are pervasively transcribed, yielding a complex transcriptome
      with high variability in composition and cellular abundance. Although recent
      efforts have identified thousands of new long non-coding (lnc) RNAs and
      demonstrated a complex transcriptional repertoire produced by protein-coding (pc)
      genes, limited progress has been made in distinguishing functional RNA from
      spurious transcription events. This is partly due to present RNA classification,
      which is typically based on technical rather than biochemical criteria. Here we
      devise a strategy to systematically categorize human RNAs by their sensitivity to
      the ribonucleolytic RNA exosome complex and by the nature of their transcription
      initiation. These measures are surprisingly effective at correctly classifying
      annotated transcripts, including lncRNAs of known function. The approach also
      identifies uncharacterized stable lncRNAs, hidden among a vast majority of
      unstable transcripts. The predictive power of the approach promises to streamline
      the functional analysis of known and novel RNAs. 

PMID- 25387875
TI  - Outcome of repeated prostatic biopsy during active surveillance: implications for
      focal therapy.
AB  - INTRODUCTION: Active surveillance (AS) is commonly recommended for men with
      localized low-intermediate-risk prostate cancer (PCa). The aim of our study was
      to assess the probability that patients with PCa would develop unfavorable
      disease features (UDF) while under AS for the purpose of evaluating whether
      immediate hemiablation therapy (HAT) could bring clinical benefit to selected
      patients. METHODS: In our cohort of AS patients, 157 were diagnosed with
      unilateral PCa. Using five different definitions of UDF, patients' data were used
      to simulate the theoretical outcome whether these patients were managed by
      immediate unilateral HAT or remained on AS. RESULTS: The mean age at the time of
      diagnosis was 67 years (range 47-81). The median follow-up was 5.4 years
      [interquartile range (IQR) 3.4-8]. Baseline characteristics included a median PSA
      value of 5.5 ng/ml (IQR 4.5-7), median number of biopsy taken of 10 (IQR 6-10),
      and maximum cancer percentage on any core of 10 (IQR 5-20). Of the 157 patients,
      144 (92 %) had a Gleason score (GS) of <=6. Using the whole range of definition
      for UDF, 10-47 % of patients developed UDF while under AS. Using baseline GS,
      maximum percentage of cancer on any core, and PSA density, we found significant
      trends for higher development of UDF for patients under AS. CONCLUSION: The
      majority of our patients did not develop UDF while under AS. Our study, thus,
      suggests that careful patient selection for focal therapy should be performed to
      avoid subjecting patients to unnecessary treatment.

PMID- 25387876
TI  - Comparison of treatment outcomes according to output voltage during shockwave
      lithotripsy for ureteral calculi: a prospective randomized multicenter study.
AB  - PURPOSE: To investigate the effect of fixed versus escalating voltage during SWL
      on treatment outcomes in patients with ureteral calculi (UC). METHODS: A
      prospective, randomized, multicenter trial was conducted on 120 patients who were
      diagnosed with a single radiopaque UC. The patients were randomized into group C
      (n = 60, constant 13 kV, 3,000 shock wave, 2 Hz) or group E (n = 60, 11.4-12.0-13
      kV per 1,000 shock waves, 2 Hz). They were evaluated by plain abdominal
      radiography and urinalysis at 1 week after a single session of SWL, and repeat
      SWL was performed if needed. The primary endpoint was stone-free rate at 1 week
      (SFR1) after SWL. Secondary endpoints were post-SWL visual pain score (VPS), oral
      analgesic requirements during 1 week, and cumulative SFRs after the second and
      third sessions of SWL. RESULTS: Groups C and E were well balanced in terms of
      baseline patients and stone characteristics, including pre-SWL VPS, stone
      location, and stone size (6.24 +/- 1.92 vs. 6.30 +/- 2.13 mm). SFR1s were not
      significantly different between groups C and E (60.0 vs. 68.3%, p = 0.447).
      Analyses stratified by stone size (<6 vs. >=6 mm) showed no difference in SFR1 (p
      = 0.148 vs. 0.808). In the analyses stratified by stone location, group E tended
      to be more effective in distal UC (81.0 vs. 50.0%, p = 0.052), whereas no
      difference was seen in proximal UC (p = 0.487). Secondary endpoints were also
      similar between the two groups. CONCLUSIONS: Our results suggest that voltage
      escalation during SWL in UC may not provide superior stone fragmentation compared
      to fixed voltage.

PMID- 25387877
TI  - Cardiovascular events associated with androgen deprivation therapy in patients
      with prostate cancer: a systematic review and meta-analysis.
AB  - CONTEXT: A recently published meta-analysis of randomized clinical trials (RCT)
      showed that androgen deprivation therapy (ADT) did not significantly increase
      cardiovascular mortality in prostate cancer patients. However, cardiovascular
      morbidity, which can impact quality of life, was not evaluated. OBJECTIVE: To
      evaluate the risk of cardiovascular morbidity associated with ADT in patients
      with prostate cancer. METHODS: We conducted a literature search from January 1960
      to June 2012. RCT and large cohort studies that evaluated first-line endocrine
      therapy and ADT longer than 6 months were screened for inclusion. RESULTS: In
      total, 126,898 patients were included in four cohort studies, and 10,760 patients
      were included in nine RCTs. Analysis of the RCTs showed no differences in the
      development of acute myocardial infarction (AMI) (OR 1.23; 95 % CI 0.92-1.64; I
      (2): 0 %) among the patients receiving ADT or not. The analysis of randomized
      studies that reported other nonfatal cardiovascular events demonstrated a
      significant increase in such events in the group receiving ADT (OR 1.55; 95 % CI
      1.09-2.20; I (2): 0 %). When the large cohort studies were included in the
      analysis, an increased risk of AMI among men with ADT was found (OR 2.01, 95 % CI
      1.90-2.13; I (2): 91,3 %). CONCLUSION: The use of ADT in prostate cancer patients
      corresponded with a significant increase in cardiovascular morbidity associated
      with AMI and with nonfatal events. Therefore, ADT is linked to a significant
      negative impact on quality of life. Periodic cardiovascular evaluation is
      required for these patients.

PMID- 25387878
TI  - Anthropometric measurements of the knee: time to make it fit.

PMID- 25387879
TI  - Thank you for 2014.

PMID- 25387880
TI  - RISAP is a TGN-associated RAC5 effector regulating membrane traffic during polar
      cell growth in tobacco.
AB  - RAC/ROP GTPases coordinate actin dynamics and membrane traffic during polar plant
      cell expansion. In tobacco (Nicotiana tabacum), pollen tube tip growth is
      controlled by the RAC/ROP GTPase RAC5, which specifically accumulates at the
      apical plasma membrane. Here, we describe the functional characterization of
      RISAP, a RAC5 effector identified by yeast (Saccharomyces cerevisiae) two-hybrid
      screening. RISAP belongs to a family of putative myosin receptors containing a
      domain of unknown function 593 (DUF593) and binds via its DUF593 to the globular
      tail domain of a tobacco pollen tube myosin XI. It also interacts with F-actin
      and is associated with a subapical trans-Golgi network (TGN) compartment, whose
      cytoplasmic position at the pollen tube tip is maintained by the actin
      cytoskeleton. In this TGN compartment, apical secretion and endocytic membrane
      recycling pathways required for tip growth appear to converge. RISAP
      overexpression interferes with apical membrane traffic and blocks tip growth.
      RAC5 constitutively binds to the N terminus of RISAP and interacts in an
      activation-dependent manner with the C-terminal half of this protein. In pollen
      tubes, interaction between RAC5 and RISAP is detectable at the subapical TGN
      compartment. We present a model of RISAP regulation and function that integrates
      all these findings. 

PMID- 25387882
TI  - Is there a single porcine protegrin gene?

PMID- 25387881
TI  - A DEK domain-containing protein modulates chromatin structure and function in
      Arabidopsis.
AB  - Chromatin is a major determinant in the regulation of virtually all DNA-dependent
      processes. Chromatin architectural proteins interact with nucleosomes to modulate
      chromatin accessibility and higher-order chromatin structure. The evolutionarily
      conserved DEK domain-containing protein is implicated in important chromatin
      related processes in animals, but little is known about its DNA targets and
      protein interaction partners. In plants, the role of DEK has remained elusive. In
      this work, we identified DEK3 as a chromatin-associated protein in Arabidopsis
      thaliana. DEK3 specifically binds histones H3 and H4. Purification of other
      proteins associated with nuclear DEK3 also established DNA topoisomerase 1alpha
      and proteins of the cohesion complex as in vivo interaction partners. Genome-wide
      mapping of DEK3 binding sites by chromatin immunoprecipitation followed by deep
      sequencing revealed enrichment of DEK3 at protein-coding genes throughout the
      genome. Using DEK3 knockout and overexpressor lines, we show that DEK3 affects
      nucleosome occupancy and chromatin accessibility and modulates the expression of
      DEK3 target genes. Furthermore, functional levels of DEK3 are crucial for stress
      tolerance. Overall, data indicate that DEK3 contributes to modulation of
      Arabidopsis chromatin structure and function. 

PMID- 25387883
TI  - Authors' response to commentary by Cheryl Kruschke and Denise Hyde.

PMID- 25387884
TI  - Worldwide Distribution of Four SNPs in X-Ray and Repair and Cross-Complementing
      Group 1 (XRCC1).
AB  - PURPOSE: X-ray repair cross-complementing group 1 (XRCC1) repairs single-strand
      breaks in DNA. Several reports have shown the association of single nucleotide
      polymorphisms (SNPs) (Arg194Trp, Pro206Pro, Arg280His, Arg399Gln) in XRCC1 to
      diseases. Limited population data are available regarding SNPs in XRCC1,
      especially in African populations. In this study, genotype distributions of four
      SNPs in worldwide populations were examined and compared with those reported
      previously. MATERIALS AND METHODS: Four SNPs (Arg194Trp, Pro206Pro, Arg280His,
      Arg399Gln) in XRCC1 from genomic DNA samples of 10 populations were evaluated by
      using polymerase chain reaction followed by restriction fragment length
      polymorphism analysis. RESULTS: The frequency of the minor allele corresponding
      to the Trp allele of XRCC1Arg194Trp was higher in Asian populations than in
      African and Caucasian populations. As for XRCC1Pro206Pro, Africans showed higher
      minor allele frequencies than did Asian populations, except for Tamils and
      Sinhalese. XRCC1 Arg280His frequencies were similar among Africans and Caucasians
      but differed among Asian populations. Similarly, lower mutant XRCC1 Arg399Gln
      frequencies were observed in Africans. CONCLUSIONS: This study is the first to
      show the existence of a certain genetic heterogeneity in the worldwide
      distribution of four SNPs in XRCC1.

PMID- 25387885
TI  - Accuracy of ultrasound for predicting pathologic response during neoadjuvant
      therapy for breast cancer.
AB  - Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer
      allows therapy to be tailored; however, optimal response assessment methods have
      not been established. We estimated the accuracy of ultrasound (US) to predict
      pathologic complete response (pCR) using common response criteria and pCR
      definitions, and estimated incremental accuracy over known prognostic variables.
      Participants undergoing US after two cycles in the GeparTrio trial randomised to
      no change in NAC were eligible. US response by World Health Organisation (WHO)
      criteria (1D or 2D) and Response Evaluation Criteria In Solid Tumours (RECIST)
      was assessed. Four pCR definitions were applied. Sensitivity (correct prediction
      of pCR), specificity (correct prediction of no-pCR) and diagnostic odds ratios
      (DORs) were calculated. Areas under the curve (AUCs) were derived from logistic
      regression including patient variables with and without US. In 832 patients, DORs
      decreased as pCR definitions became less stringent (p = 0.01). For WHO-2D, DORs
      were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/is,ypN+/-) and
      2.65 (ypT0/is/1a,ypN+/-). DORs did not differ between US criteria (p = 0.60).
      High sensitivity and lower specificity were found for WHO-2D and RECIST; WHO-1D
      was highly specific with low sensitivity. Sensitivity was highest for WHO-2D
      predicting ypT0,ypN0 (sensitivity = 81.7%, specificity = 47.6% vs. 42.3% and
      80.4% for WHO-1D). Adding US to models including patient variables (age, T-stage,
      histology and subtype) improved AUCs for predicting pCR by 2-3%. In conclusion,
      US accuracy is highest for predicting ypT0,ypN0, shown to be most prognostic of
      long-term survival. WHO-2D and RECIST maximise sensitivity; WHO-1D maximises
      specificity. US modestly improves the prediction of pCR by patient
      characteristics. 

PMID- 25387886
TI  - Alu elements and the phylogeny of capuchin (Cebus and Sapajus) monkeys.
AB  - Three families of New World monkeys, the Pitheciidae, Atelidae, and Cebidae, are
      currently recognized. The monophyly of the Cebidae is supported unequivocally by
      the presence of ten unique Alu elements, which are absent from the other two
      families. In this paper, the five genomic regions containing these Alu elements
      were sequenced in specimens representing nine capuchin (Cebus, Sapajus) species
      in order to identify mutations that may help elucidate the taxonomy and
      phylogenetic relationships of the cebids. The results confirmed the presence of
      previously described Alu elements in the capuchins. An Alu insertion present in
      the Cebidae2 genomic region belonging to the AluSc subfamily was amplified and
      sequenced only in Sapajus. No amplified or unspecific product was obtained for
      all other species studied here. An AluSc insertion present in the CeSa1 region
      was found only in Cebus, Sapajus, and Saimiri. Cebidae4 was characterized by two
      insertions, an AluSz6 shared by all cebids, and a complete SINE (AluSx3) found
      only in the capuchins (Cebus and Sapajus). The genomic region Cebidae5 revealed
      two insertion events, one of the AluSx subfamily, which was shared by all cebids,
      and another (AluSc8), that was unique to Cebus, offering a straightforward
      criterion for the differentiation of the two genera, Cebus and Sapajus. The
      Cebidae6 region showed four distinct insertion events: a 52-bp simple repeat
      ((TATG) n), two very ancient repeats (MIRc) and a TcMar-Tigger shared by all New
      World monkeys studied so far, and an Alu insertion of the AluSx subfamily present
      exclusively in the cebids. The phylogenetic tree confirmed the division of the
      capuchins into two genera, Cebus and Sapajus, and suggested the southern species
      Sapajus nigritus robustus and S. cay as the earliest and second earliest
      offshoots in this genus, respectively. This supports a southern origin for the
      Sapajus radiation.

PMID- 25387887
TI  - Translational regulation during stage transitions in malaria parasites.
AB  - The complicated life cycle of the malaria parasite involves a vertebrate host and
      a mosquito vector, and translational regulation plays a prominent role in
      orchestrating the developmental events in the two transition stages: gametocytes
      and sporozoites. Translational regulation is executed in both global and
      transcript-specific manners. Plasmodium uses a conserved mechanism involving
      phosphorylation of eIF2alpha to repress global protein synthesis during the
      latent period of sporozoite development in the mosquito salivary glands.
      Transcript-specific translational regulation is achieved by a network of RNA
      binding proteins (RBPs), among which the Dhh1 RNA helicase DOZI and Puf family
      RBPs are by far the best studied in Plasmodium. While the DOZI complex defines a
      new P granule with a role in protecting certain gametocyte mRNAs from
      degradation, the Puf proteins appear to repress expression of mRNAs in both
      gametocytes and sporozoites. These examples underscore the significance of
      translational regulation in Plasmodium development. 

PMID- 25387890
TI  - Scalable room-temperature synthesis of mesoporous nanocrystalline ZnMn2O4 with
      enhanced lithium storage properties for lithium-ion batteries.
AB  - In this work, we put forward a facile yet efficient room-temperature synthetic
      methodology for the smart fabrication of mesoporous nanocrystalline ZnMn2O4 in
      macro-quality from the birnessite-type MnO2 phase. A plausible reduction/ion
      exchange/re-crystallization mechanism is tentatively proposed herein for the
      scalable synthesis of the spinel phase ZnMn2O4. When utilized as a high
      performance anode for advanced Li-ion battery (LIB) application, the as
      synthesized nanocrystalline ZnMn2O4 delivered an excellent discharge capacity of
      approximately 1288 mAh g(-1) on the first cycle at a current density of 400 mA g(
      1), and exhibited an outstanding cycling durability, rate capability, and
      coulombic efficiency, benefiting from its mesoporous and nanoscale structure,
      which strongly highlighted its great potential in next-generation LIBs.
      Furthermore, the strategy developed here is very simple and of great importance
      for large-scale industrial production.

PMID- 25387888
TI  - Effect of prasugrel in patients with asthma: results of PRINA, a randomized,
      double-blind, placebo-controlled, cross-over study.
AB  - BACKGROUND: Although experimental studies have demonstrated that platelets are
      proinflammatory cells, no randomized studies have tested the anti-inflammatory
      effect of antiplatelet agents in humans. The platelet P2Y12 receptors mediated
      bronchial inflammation in a mouse model of asthma, suggesting that P2Y12
      represents a pharmacologic target for asthma. OBJECTIVES: In this proof-of
      concept, placebo-controlled, randomized, cross-over study, we tested the effects
      of the P2Y12 antagonist prasugrel on bronchial hyperreactivity of asthmatic
      patients. PATIENTS/METHODS: Twenty-six asthmatic patients were randomly and
      blindly allocated to prasugrel (10 mg once daily) or placebo for 15 days. After a
      >= 15-day wash-out, patients were crossed over to the alternative treatment.
      Before and after each treatment, patients underwent a bronchial provocation test
      with mannitol and measurement of fractional exhaled nitric oxide (FeNO).
      Inhibition of P2Y12 -dependent platelet reactivity (platelet reactivity index
      [PRI]) was measured with the vasodilator-stimulated phosphoprotein
      phosphorylation assay. RESULTS: The provocative dose of mannitol causing a 15%
      drop in forced expiratory volume in 1 s increased from 142 mg (95% confidence
      interval [CI] 82-202) to 187 mg (95% CI 113-262) after prasugrel treatment (P =
      0.09), and did not change after placebo treatment (136 mg [95% CI 76-196] and 144
      mg [95% CI 84-204], P = 0.65). FeNO did not change after either treatment. The
      PRI decreased from 80% (95% CI 77-83) to 23% (95% CI 7-29) after prasugrel
      treatment (P < 0.001) and remained unchanged after placebo. CONCLUSIONS: Our
      proof-of-concept, randomized, controlled study is the first one to test in vivo
      the anti-inflammatory effects of platelet inhibition in human patients. The
      results suggest that pharmacologic inhibition of P2Y12 receptors may slightly
      reduce the bronchial inflammatory burden, and lay the groundwork for further
      studies, with clinical endpoints.

PMID- 25387891
TI  - Real-time optical diagnosis for diminutive colorectal polyps using narrow-band
      imaging: the VALID randomised clinical trial.
AB  - BACKGROUND: Diminutive (<= 5 mm) colorectal polyps are common, and overwhelmingly
      benign. Routinely, after polypectomy, they are examined pathologically to
      determine the surveillance intervals. Advances in equipment and techniques, such
      as narrow-band imaging (NBI) colonoscopy, now permit reliable real-time optical
      diagnosis. METHODS: We conducted a randomised single-masked study involving three
      institutions to determine whether optical diagnosis of diminutive colorectal
      polyps meets clinical practice standards and reduces the need for histopathology.
      We randomly assigned eligible patients undergoing routine high-definition
      colonoscopy to optical diagnosis using near focus versus standard view, using
      computer-generated block sequence. By validated criteria, we rendered an optical
      diagnosis and a confidence level (high vs low) for all polyps, using NBI. Our
      primary endpoint was the number of accurate high-confidence optical diagnoses
      compared with central blinded pathology in the two groups. We analysed data using
      intention to treat. FINDINGS: We enrolled 558 subjects, and randomly assigned 281
      to near focus and 277 to standard view optical diagnosis. We detected 1309
      predominantly diminutive (74.5%) and neoplastic (60.0%) polyps. Endoscopists were
      significantly more likely, OR 2.2 (95% CI 1.6 to 3.0, p<0.0001), to make a high
      confidence optical diagnosis with near focus (85.1%) than standard (72.6%) view.
      High-confidence diagnoses had 96.4% and 92.0% negative predictive value,
      respectively. Of all polyps, 75.3% (95% CI71.3% to 78.9%) had a high-confidence
      accurate prediction using near focus, compared with 63.1% (95% CI 58.5% to 67.6%)
      using standard view. Optical versus histopathological diagnosis showed excellent
      agreement between the surveillance intervals, 93.5% in near focus and 92.2% in
      standard view. The median diagnosis time was 14 s. CONCLUSIONS: Real-time optical
      diagnosis using NBI colonoscopy may replace the pathology diagnosis for the
      majority of diminutive colorectal polyps. Using colonoscopy with near focus view
      increases the confidence level of the optical diagnosis. Optical diagnosis would
      be a paradigm shift in clinical practice of colonoscopy for colorectal cancer
      screening. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01288833.

PMID- 25387892
TI  - Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor
      effector/memory CD8 T cells in a poorly immunogenic tumor model.
AB  - Immunotherapies targeting the programmed death 1 (PD-1) coinhibitory receptor
      have shown great promise for a subset of patients with cancer. However, robust
      and safe combination therapies are still needed to bring the benefit of cancer
      immunotherapy to broader patient populations. To search for an optimal strategy
      of combinatorial immunotherapy, we have compared the antitumor activity of the
      anti-4-1BB/anti-PD-1 combination with that of the anti-PD-1/anti-LAG-3
      combination in the poorly immunogenic B16F10 melanoma model. Pronounced tumor
      inhibition occurred only in animals receiving anti-PD-1 and anti-4-1BB
      concomitantly, while combining anti-PD-1 with anti-LAG-3 led to a modest degree
      of tumor suppression. The activity of the anti-4-1BB/anti-PD-1 combination was
      dependent on IFNgamma and CD8(+) T cells. Both 4-1BB and PD-1 proteins were
      elevated on the surface of CD8(+) T cells by anti-4-1BB/anti-PD-1 cotreatment. In
      the tumor microenvironment, an effective antitumor immune response was induced as
      indicated by the increased CD8(+)/Treg ratio and the enrichment of genes such as
      Cd3e, Cd8a, Ifng, and Eomes. In the spleen, the combination treatment shaped the
      immune system to an effector/memory phenotype and increased the overall activity
      of tumor-specific CD8(+) CTLs, reflecting a long-lasting systemic antitumor
      response. Furthermore, combination treatment in C57BL/6 mice showed no additional
      safety signals, and only minimally increased severity of the known toxicity
      relative to 4-1BB agonist alone. Therefore, in the absence of any cancer vaccine,
      anti-4-1BB/anti-PD-1 combination therapy is sufficient to elicit a robust
      antitumor effector/memory T-cell response in an aggressive tumor model and is
      therefore a candidate for combination trials in patients.

PMID- 25387893
TI  - Afucosylated antibodies increase activation of FcgammaRIIIa-dependent signaling
      components to intensify processes promoting ADCC.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) is a key mechanism by which
      therapeutic antibodies mediate their antitumor effects. The absence of fucose on
      the heavy chain of the antibody increases the affinity between the antibody and
      FcgammaRIIIa, which results in increased in vitro and in vivo ADCC compared with
      the fucosylated form. However, the cellular and molecular mechanisms responsible
      for increased ADCC are unknown. Through a series of biochemical and cellular
      studies, we find that human natural killer (NK) cells stimulated with
      afucosylated antibody exhibit enhanced activation of proximal FcgammaRIIIa
      signaling and downstream pathways, as well as enhanced cytoskeletal rearrangement
      and degranulation, relative to stimulation with fucosylated antibody.
      Furthermore, analysis of the interaction between human NK cells and targets using
      a high-throughput microscope-based antibody-dependent cytotoxicity assay shows
      that afucosylated antibodies increase the number of NK cells capable of killing
      multiple targets and the rate with which targets are killed. We conclude that the
      increase in affinity between afucosylated antibodies and FcgammaRIIIa enhances
      activation of signaling molecules, promoting cytoskeletal rearrangement and
      degranulation, which, in turn, potentiates the cytotoxic characteristics of NK
      cells to increase efficiency of ADCC.

PMID- 25387894
TI  - Immunity to the vacuolar ATPase complex accessory unit ATP6S1 in patients with
      malignant melanoma.
AB  - The augmentation of high-titer antibodies to ATP6S1 is associated with favorable
      clinical outcomes in patients who received vaccination with autologous,
      irradiated tumor cells engineered to secrete GM-CSF and allogeneic bone marrow
      transplantation. Cellular immune responses to ATP6S1 are unknown. To define its
      role as an immune target, examination of cellular responses to ATP6S1 and
      immunity related to current therapies such as checkpoint blockade is needed. We
      used an overlapping peptide library representing the full-length ATP6S1 protein
      to screen for cellular responses from the peripheral blood of patients with stage
      III and IV melanoma. Reactive peptide pools were used to determine the individual
      peptide activity and epitopes. Recombinant ATP6S1 protein was used in an ELISA to
      assess potential correlation with humoral immune responses and changes in
      immunity related to CTLA-4 blockade with ipilimumab in these patients. We
      observed a broad array of CD4(+) and CD8(+) cellular responses against ATP6S1,
      including the identification of several MHC class I and II ATP6S1 epitopes. The
      generation of specific CD4(+) and cytotoxic T cells revealed potent functional
      capability elicited by ipilimumab treatment in patients with metastatic melanoma,
      which revealed potent functional capability, including cytokine production,
      proliferation responsiveness to melanoma cell lines, and tumor-cell killing.
      Furthermore, the augmented humoral immune responses to ATP6S1 as a function of
      ipilimumab treatment were associated with beneficial clinical outcomes. These
      results support the continued development of ATP6S1 as a biomarker and
      therapeutic target.

PMID- 25387895
TI  - Severe adverse immunologic reaction in a patient with glioblastoma receiving
      autologous dendritic cell vaccines combined with GM-CSF and dose-intensified
      temozolomide.
AB  - Therapeutic vaccination of patients with cancer-targeting tumor-associated
      antigens is a promising strategy for the specific eradication of invasive
      malignancies with minimal toxicity to normal tissues. However, as increasingly
      potent modalities for stimulating immunologic responses are developed for
      clinical evaluation, the risk of inflammatory and autoimmune toxicities also may
      be exacerbated. In this report, we describe the induction of a severe (grade 3)
      immunologic reaction in a patient with newly diagnosed glioblastoma (GBM)
      receiving autologous RNA-pulsed dendritic cell (DC) vaccines admixed with GM-CSF
      and administered coordinately with cycles of dose-intensified temozolomide.
      Shortly after the eighth administration of the admixed intradermal vaccine, the
      patient experienced dizziness, flushing, conjunctivitis, headache, and the
      outbreak of a disseminated macular/papular rash and bilateral indurated injection
      sites. Immunologic workup of patient reactivity revealed sensitization to the GM
      CSF component of the vaccine and the production of high levels of anti-GM-CSF
      autoantibodies during vaccination. Removal of GM-CSF from the DC vaccine allowed
      continued vaccination without incident. Despite the known lymphodepletive and
      immunosuppressive effects of temozolomide, these observations demonstrate the
      capacity for the generation of severe immunologic reactivity in patients with GBM
      receiving DC-based therapy during adjuvant dose-intensified temozolomide.

PMID- 25387897
TI  - Effects of homeopathic mother tinctures on breath alcohol testing.
AB  - In some countries, it is illegal to drive with any detectable amount of alcohol
      in blood; in others, the legal limit is 0.5 g/L or lower. Recently, some
      defendants charged with driving under the influence of alcohol and have claimed
      that positive breath alcohol test results were due to the ingestion of
      homeopathic mother tinctures. These preparations are obtained by maceration,
      digestion, infusion, or decoction of herbal material in hydroalcoholic solvent. A
      series of tests were conducted to evaluate the alcoholic content of three
      homeopathic mother tinctures and their ability to produce inaccurate breath
      alcohol results. Nine of 30 subjects gave positive results (0.11-0.82 g/L) when
      tests were taken within 1 min after drinking mother tincture. All tests taken at
      least 15 min after the mother tincture consumption and resulted in alcohol-free
      readings. An observation period of 15-20 min prior to breath alcohol testing
      eliminates the possibility of false-positive results.

PMID- 25387896
TI  - Vitamin C treatment attenuates hemorrhagic shock related multi-organ injuries
      through the induction of heme oxygenase-1.
AB  - BACKGROUND: Vitamin C (VitC) has recently been shown to exert beneficial effects,
      including protecting organ function and inhibiting inflammation, in various
      critical care conditions, but the specific mechanism remains unclear. Induction
      of heme oxygenase (HO)-1, a heat shock protein, has been shown to prevent organ
      injuries in hemorrhagic shock (HS) but the relationship between VitC and HO-1 are
      still ill-defined so far. Here we conducted a systemic in vivo study to
      investigate if VitC promoted HO-1 expression in multiple organs, and then tested
      if the HO-1 induction property of VitC was related to its organ protection and
      anti-inflammatory effect. METHODS: Firstly, to determine the HO-1 induction
      property of VitC, the HO-1 level were measured in tissues including kidney, liver
      and lung of the normal and HS model of Sprague-Dawley (SD) rats after VitC
      treatment (100 mg/kg body weight). Secondly, to testify if VitC prevented HS
      related organ injuries via inducing HO-1, the HS model of rats were separately
      pre- and post-treated with VitC, and some of them also received Zinc
      protoporphyrin (Znpp), a specific HO-1 inhibitor. The HO-1 activity in tissues
      was tested; the organ injuries (as judged by histological changes in tissues and
      the biochemical indicators level in serum) and inflammatory response in tissues
      (as judged by the level of pro-inflammatory cytokines Tumor necrosis factor-alpha
      and Interleukin-6 ) were analyzed. RESULTS: The HO-1 mRNA and protein level in
      kidney, liver, and lung were highly induced by VitC treatement under normal and
      HS conditions. The HO-1 activity in tissues was enhanced by both VitC pre- and
      post-treatment, which was shown to improve the organ injuries and inhibit the
      inflammatory response in the HS model of rats. Of note, the beneficial effects of
      VitC were abolished after HO-1 activity was blocked by Znpp. CONCLUSIONS: VitC
      led to a profound induction of HO-1 in multiple organs including the kidney,
      liver and lung, and this property might be responsible for the organ protection
      and inflammation inhibitory effects of both pre- and post-treatment with VitC in
      HS.

PMID- 25387898
TI  - Demographic and clinical features of autoimmune thyroid disorder in Japanese
      patients with systemic sclerosis.
AB  - Autoimmune thyroid disorders (AITD) are characterized by the impairment of the
      thyroid gland as a result of systemic or organ-specific autoimmune disorders, and
      the presence of antithyroid autoantibodies, such as antithyroglobulin antibody
      (AbTg) and antithyroid peroxidase antibody (AbTPO). Several studies have reported
      the association of AITD with systemic sclerosis (SSc). However, none of those
      studies analyzed the association between AITD and skin sclerosis in SSc patients.
      The aim of this study was to examine the demographic and clinical features of SSc
      patients with AITD treated in our department. Of a total of 210 SSc patients, we
      identified 30 with AITD (14.3%), including 29 with Hashimoto's disease (13.8%)
      and one patient with Graves' disease (0.5%), indicating that hypothyroidism was
      more common among SSc patients with AITD. All patients with AITD were female, and
      anticentromere antibody positivity, the complication of Sjogren's syndrome,
      severe facial skin sclerosis and atrophy of the thyroid gland were significantly
      prevalent in SSc patients with AITD. SSc patients with such clinical features may
      be at high risk of AITD and require regular follow up of thyroid function
      including ultrasonography and the examination of serum hormone levels to start an
      early treatment. 

PMID- 25387899
TI  - The association between a biomarker score for fruit and vegetable intake and
      incident type 2 diabetes: the EPIC-Norfolk study.
AB  - BACKGROUND/OBJECTIVES: Biomarkers for a mixed fruit and vegetable (FV) diet are
      needed to provide a better understanding of the association between FV intake and
      type 2 diabetes. We aimed to examine the prospective association between a
      composite score comprised of three biomarkers of FV intake in free-living
      populations and incident diabetes. SUBJECTS/METHODS: A total of 318 incident
      diabetes cases and 926 controls from the EPIC (European Prospective Investigation
      of Cancer)-Norfolk study aged 40-79 years at baseline (1993-1997), completed 7
      day prospective food diary and had plasma vitamin C and carotenoid measures. A
      composite biomarker score (CB-score) comprising the sum of plasma vitamin C, beta
      carotene and lutein was derived. Odds ratios (ORs) and 95% confidence intervals
      (CIs) for incident diabetes were estimated using multivariable logistic
      regression. RESULTS: A strong inverse association was found between the CB-score
      and incident diabetes. The ORs (95% CI) of diabetes comparing quartiles Q2, Q3
      and Q4 of the CB-score with Q1 (reference category) were 0.70 (0.49, 1.00), 0.34
      (0.23, 0.52) and 0.19 (0.12, 0.32), respectively, and 0.49 (0.40, 0.58) per s.d.
      change in CB-score in a model adjusted for demographic and lifestyle factors. The
      association was marginally attenuated after additionally adjusting for body mass
      index and waist circumference (0.60 (0.49 and 0.74) per s.d. change in CB-score).
      CONCLUSIONS: A combination of biomarkers representing the intake of a mixed FV
      diet was strongly inversely associated with incident diabetes. These findings
      provide further support for measuring dietary biomarkers in studies of diet
      disease associations and highlight the importance of consuming FV for the
      prevention of diabetes.

PMID- 25387900
TI  - Refeeding encephalopathy in a patient with severe hypophosphataemia and
      hyperammonaemia.
AB  - The refeeding syndrome is a potentially fatal condition that affects multiple
      organ systems. It is the consequence of fluid and electrolyte shifts that may
      occur in a malnourished patient following the introduction of nutrition therapy.
      The most prominent characteristic is hypophosphataemia. Although hyperammonaemia
      is usually seen in decompensated liver cirrhosis or acute liver failure, it may
      occur in other settings. We report a clinical case of prolonged and severe
      encephalopathy accompanied by hypophosphataemia and hyperammonaemia in a 59-year
      old woman with no preexisting liver disease, urea cycle defects or portosystemic
      shunting. We suggest that these biochemical abnormalities were caused by
      uncontrolled refeeding and that the clinical picture was consistent with
      refeeding encephalopathy. 

PMID- 25387901
TI  - Dietary fiber effects in chronic kidney disease: a systematic review and meta
      analysis of controlled feeding trials.
AB  - BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) is a major health concern
      associated with increased risk of cardiovascular disease, morbidity and
      mortality. Current CKD practice guidelines overlook dietary fiber, which is
      chronically low in the renal diet. However, increasing dietary fiber has been
      proposed to ameliorate the progress of CKD. We therefore conducted a systematic
      review and meta-analysis on the effect of dietary fiber intake on serum urea and
      creatinine as classical markers of renal health in individuals with CKD.
      SUBJECTS/METHODS: We searched MEDLINE, EMBASE, CINHAL and the Cochrane Library
      for relevant clinical trials with a follow-up ?7 days. Data were pooled by the
      generic inverse variance method using random-effects models and expressed as mean
      difference (MD) with 95% confidence intervals (95% CIs). Heterogeneity was
      assessed by the Cochran Q statistic and quantified by I(2). RESULTS: A total of
      14 trials involving 143 participants met the eligibility criteria. Dietary fiber
      supplementation significantly reduced serum urea and creatinine levels in the
      primary pooled analyses (MD, -1.76 mmol/l (95% CI, -3.00, -0.51), P<0.01 and MD, 
      22.83 mmol/l (95% CI, -42.63, -3.02), P=0.02, respectively) with significant
      evidence of interstudy heterogeneity only in the analysis of serum urea.
      CONCLUSIONS: This is the first study to summarize the potential beneficial
      effects of dietary fiber in the CKD population demonstrating a reduction in serum
      urea and creatinine, as well as highlighting the lack of clinical trials on
      harder end points. Larger, longer, higher-quality clinical trials measuring a
      greater variety of uremic toxins in CKD are required (NCT01844882).

PMID- 25387902
TI  - Dietary phytochemical index is inversely associated with the occurrence of
      hypertension in adults: a 3-year follow-up (the Tehran Lipid and Glucose Study).
AB  - BACKGROUND/OBJECTIVE: The epidemiological association of phytochemical-rich foods
      with the risk of hypertension is unclear. This study aimed to determine the
      association of dietary phytochemical index (PI) with the occurrence of
      hypertension (HTN) after 3 years of follow-up in Tehranian adults.
      SUBJECTS/METHODS: This prospective study was conducted on 1546 nonhypertensive
      subjects, aged 20-70 years. Dietary intake was collected by validated
      semiquantitative food frequency questionnaire (FFQ). Dietary PI was calculated as
      (dietary energy derived from phytochemical-rich foods (kcal)/total daily energy
      intake (kcal)) * 100. Blood pressure was measured at baseline and after 3 years
      of follow-up and HTN was defined by Joint National Committee on prevention,
      detection, evaluation and treatment of high blood pressure criteria. The odds of
      HTN after 3 years in each quartile category of dietary PI were estimated by
      logistic regression model and adjusted for potential variables. RESULTS: The mean
      age of participants was 38.0+/-12.0 years and 43% were male. The mean dietary PI
      was 29.1+/-11.8. After 3 years of follow-up, 265 (17.1%) new cases of HTN were
      identified. No significant changes were observed in the systolic and diastolic
      blood pressure across quartile categories of dietary PI. After adjustment for
      confounders, the odds (95% confidence interval) of HTN across quartiles of
      dietary PI were 1.00, 0.97 (0.62-1.38), 0.69 (0.45-1.07) and 0.52 (0.32-0.84) (P
      for trend=0.004). CONCLUSIONS: Consumption of phytochemical-rich foods may
      prevent the development of HTN. Further investigations are, however, recommended.

PMID- 25387904
TI  - Self-organisation of size-selected Co(x)Pt(1-x) clusters on graphite.
AB  - Sub-monolayer thin film morphologies obtained by deposition of size-selected
      CoxPt1-x clusters on graphite have been analyzed for different values of x. In
      all cases, the preformed clusters can easily diffuse on the surface and gather to
      form islands of clusters. By changing the cluster stoichiometry, very different
      morphologies can be obtained, going from large ramified islands to "bunches" of
      non-contacting incident clusters. We put into evidence that the introduction of
      platinum atoms in the incident particles drastically changes the interaction
      between clusters and offers the opportunity to control the coalescence process
      between them. In this way, by modifying the cluster reactivity, a local self
      organization of size-selected magnetic nanoparticles can be achieved. 

PMID- 25387903
TI  - Test of "Facilitation" vs. "Proximal Process" Moderator Models for the Effects of
      Multisystemic Therapy on Adolescents with Severe Conduct Problem.
AB  - The present study identified moderators of Multisystemic Therapy's (MST) effects
      on adolescent conduct problems, considering facilitation and proximal process
      moderation models. The sample included 164 adolescents (mean age = 14.6 years;
      83% male) randomly assigned to receive MST or services as usual; parent, youth,
      and teacher reports of adolescent functioning were obtained. A number of
      significant moderators were identified. Proximal process moderation patterns were
      identified (e.g., families with parents with lower levels of adaptive child
      discipline skills gained more from MST), but the majority of significant
      interactions showed a facilitation moderation pattern with, for instance, higher
      levels of adaptive functioning in families and parents appearing to facilitate
      MST (i.e., greater benefits from MST were found for these families). This
      facilitation pattern may reflect such families being more capable of and/or more
      motivated to use the resources provided by MST. It is suggested that factors
      consistently identified as facilitation moderators may serve as useful foci for
      MST's strength-based levers of change approach. Other implications of these
      findings for individualized treatment also are discussed.

PMID- 25387905
TI  - Theoretical and computational investigations of nanoparticle-biomembrane
      interactions in cellular delivery.
AB  - With the rapid development of nanotechnology, nanoparticles have been widely used
      in many applications such as phototherapy, cell imaging, and drug/gene delivery.
      A better understanding of how nanoparticles interact with bio-system (especially
      cells) is of great importance for their potential biomedical applications. In
      this review, the current status and perspective of theoretical and computational
      investigations is presented on the nanoparticle-biomembrane interactions in
      cellular delivery. In particular, the determining parameters (including the
      properties of nanoparticles, cell membranes and environments) that govern the
      cellular uptake of nanoparticles (direct penetration and endocytosis) are
      discussed. Further, some special attention is paid to their interactions beyond
      the translocation of nanoparticles across membranes (e.g., nanoparticles escaping
      from endosome and entering into nucleus). Finally, a summary is given, and the
      challenging problems of this field in the future are identified. 

PMID- 25387907
TI  - Phase reconstruction in annular bright-field scanning transmission electron
      microscopy.
AB  - A novel technique for reconstructing the phase shifts of electron waves was
      applied to Cs-corrected scanning transmission electron microscopy (STEM). To
      realize this method, a new STEM system equipped with an annular aperture,
      annularly arrayed detectors and an arrayed image processor has been developed and
      evaluated in experiments. We show a reconstructed phase image of graphite
      particles and demonstrate that this new method works effectively for high
      resolution phase imaging.

PMID- 25387908
TI  - Bergmann's Rule rules body size in an ectotherm: heat conservation in a lizard
      along a 2200-metre elevational gradient.
AB  - Bergmann's Rule predicts larger body sizes in colder habitats, increasing
      organisms' ability to conserve heat. Originally formulated for endotherms, it is
      controversial whether Bergmann's Rule may be applicable to ectotherms, given that
      larger ectotherms show diminished capacity for heating up. We predict that
      Bergmann's Rule will be applicable to ectotherms when the benefits of a higher
      conservation of heat due to a larger body size overcompensate for decreased
      capacity to heating up. We test this hypothesis in the lizard Psammodromus
      algirus, which shows increased body size with elevation in Sierra Nevada (SE
      Spain). We measured heating and cooling rates of lizards from different
      elevations (from 300 to 2500 m above sea level) under controlled conditions. We
      found no significant differences in the heating rate along an elevational
      gradient. However, the cooling rate diminished with elevation and body size:
      highland lizards, with larger masses, have a higher thermal inertia for cooling,
      which allows them to maintain heat for more time and keep a high body temperature
      despite the lower thermal availability. Consequently, the net gaining of heat
      increased with elevation and body size. This study highlights that the heat
      conservation mechanism for explaining Bergmann's Rule works and is applicable to
      ectotherms, depending on the thermal benefits and costs associated with larger
      body sizes.

PMID- 25387906
TI  - RhoA and membrane fluidity mediates the spatially polarized Src/FAK activation in
      response to shear stress.
AB  - While Src plays crucial roles in shear stress-induced cellular processes, little
      is known on the spatiotemporal pattern of high shear stress (HSS)-induced Src
      activation. HSS (65 dyn/cm(2)) was applied on bovine aortic endothelial cells to
      visualize the dynamic Src activation at subcellular levels utilizing a membrane
      targeted Src biosensor (Kras-Src) based on fluorescence resonance energy transfer
      (FRET). A polarized Src activation was observed with higher activity at the side
      facing the flow, which was enhanced by a cytochalasin D-mediated disruption of
      actin filaments but inhibited by a benzyl alcohol-mediated enhancement of
      membrane fluidity. Further experiments revealed that HSS decreased RhoA activity,
      with a constitutively active RhoA mutant inhibiting while a negative RhoA mutant
      enhancing the HSS-induced Src polarity. Cytochalasin D can restore the polarity
      in cells expressing the active RhoA mutant. Further results indicate that HSS
      stimulates FAK activation with a spatial polarity similar to Src. The inhibition
      of Src by PP1, as well as the perturbation of RhoA activity and membrane
      fluidity, can block this HSS-induced FAK polarity. These results indicate that
      the HSS-induced Src and subsequently FAK polarity depends on the coordination
      between intracellular tension distribution regulated by RhoA, its related actin
      structures and the plasma membrane fluidity.

PMID- 25387909
TI  - NMR in the design of antibacterials.
AB  - One of the most challenging areas in drug design is the area of new antibacterial
      drugs. Despite significant progress in target validation and screening programs,
      discovery of new antibacterial classes is not keeping pace with the growing
      threat of bacterial resistance. In this review we describe examples of the use of
      NMR spectroscopy methods in different phases of antibacterial drug design. First,
      several frequently used liquid and solid-state NMR techniques are presented,
      followed by a review and discussion of the application of NMR spectroscopy to the
      discovery of new antibacterial agents. 

PMID- 25387910
TI  - Staying healthy from fibromyalgia is ongoing hard work.
AB  - Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain condition. Although
      studies have reported that some patients can become healthy again, little is
      known about what they tell about their lives after having FMS. In this study, we
      interviewed eight Norwegian women who had all recovered from FMS about their
      experiences when ill and subsequently being healthy. Inspired by narrative
      methods, we then conducted a thematic narrative analysis. The findings indicate
      that although women reported that life was better than before, they also reported
      investing considerable effort in remaining healthy. When ill, they struggled to
      maintain the routines of everyday life. Being healthy again, they put great
      effort into avoiding illness through diet, exercise, and relaxation. In
      conclusion, remaining healthy requires ongoing hard work to maintain the body, as
      well as profound changes in everyday life. At the same time, the narratives show
      continuity in the informants' self-presentation as hard-working women. 

PMID- 25387911
TI  - Bundles of Norms About Teen Sex and Pregnancy.
AB  - Teen pregnancy is a cultural battleground in struggles over morality, education,
      and family. At its heart are norms about teen sex, contraception, pregnancy, and
      abortion. Analyzing 57 interviews with college students, we found that "bundles"
      of related norms shaped the messages teens hear. Teens did not think their
      communities encouraged teen sex or pregnancy, but normative messages differed
      greatly, with either moral or practical rationalizations. Teens readily
      identified multiple norms intended to regulate teen sex, contraception, abortion,
      childbearing, and the sanctioning of teen parents. Beyond influencing teens'
      behavior, norms shaped teenagers' public portrayals and post hoc justifications
      of their behavior. Although norm bundles are complex to measure, participants
      could summarize them succinctly. These bundles and their conflicting behavioral
      prescriptions create space for human agency in negotiating normative pressures.
      The norm bundles concept has implications for teen pregnancy prevention policies
      and can help revitalize social norms for understanding health behaviors. 

PMID- 25387912
TI  - "To teach them this art".

PMID- 25387913
TI  - Eating disorders in general practice.

PMID- 25387918
TI  - [Re: When physicians find drugs].

PMID- 25387919
TI  - [Re: When the patient refuses blood transfusion].

PMID- 25387920
TI  - [Re: Disease mongering].

PMID- 25387921
TI  - [Re: Irksome students].

PMID- 25387922
TI  - [Norwegian translation of assessment tool for alcohol withdrawal].

PMID- 25387923
TI  - [The user knows best where the shoe pinches].

PMID- 25387924
TI  - [All sick newborns should receive single rooms].

PMID- 25387925
TI  - Is there a future for state health monopolies?

PMID- 25387926
TI  - [Implementation of guidelines for PSA testing in general practice].

PMID- 25387928
TI  - Patients' experience of their general practitioner's follow-up of serious eating
      disorders.
AB  - BACKGROUND: An eating disorder is an illness that may take a life-threatening
      course. The health authorities recommend that general practitioners (GPs) should
      be included in the treatment apparatus. The patients' feelings of shame, denial
      of the illness and ambivalence with regard to treatment are disease-specific
      characteristics that need to be considered. MATERIAL AND METHOD: At two
      specialised units for eating disorders, patients aged over 18 were handed a
      questionnaire at the start of their treatment. The questionnaire dealt with GP
      consultations in which the eating disorder had been discussed. An active GP
      patient relationship was defined based on whether the patient had seen the GP at
      least three times, whether the GP's office was in proximity to the patient's
      place of residence and whether the eating disorder had been discussed during the
      past year. RESULTS: Altogether 114 patients (90%) took part in the study. 66% had
      an active GP-patient relationship, and 65% of these had discussed with their GP
      the impact of the disease on their daily lives. Altogether 75% were satisfied
      with the GP's manner, 47% found the GP to be an important supporter of their
      treatment and 44% visited their GP if their condition worsened. Those patients
      who were severely underweight and patients with GPs who demonstrated commitment
      scored highest on satisfaction and support. A total of 39% of those who had
      experience of treatment in which their current GP could have been involved in
      collaboration with the second-line service had found such involvement to be the
      case. INTERPRETATION: The patients had varying experience of follow-up provided
      by their GPs. Commitment on the part of the GP appears to result in closer follow
      up and greater patient satisfaction.

PMID- 25387929
TI  - Communication about symptoms of eating disorders in the general practitioner
      surgery.
AB  - BACKGROUND: An eating disorder is a complex disease in which the patient subjects
      his or her body to the various eating disorder symptoms in the absence of other
      ways of dealing with everyday life. There are seven symptoms of an eating
      disorder that generally appear in different combinations from one period to
      another in one and the same patient. Feelings of shame may cause information on
      symptoms to be withheld. MATERIAL AND METHOD: Patients aged 18 and above with
      serious eating disorders responded anonymously to a questionnaire before entering
      treatment in two specialist departments. The main focus was on whether the
      patient had talked with a general practitioner (GP) about relevant eating
      disorder symptoms and ailments that could be related to the eating disorder.
      RESULTS: Altogether 114 patients participated (of which three were men). A total
      of 91 (80%) had discussed the eating disorder with their GP during the past year.
      Of these, 67% of those who had reduced their food intake over the past year had
      discussed this with their GP. Altogether 68% of those who had vomited and 33% of
      those who had over-exercised had communicated this. None of the respondents had
      revealed their use of diuretic or weight-loss drugs to their GP. 85% of
      respondents stated that the GP must ask specifically about each symptom of an
      eating disorder in order to reveal these. At least half had discussed the
      association between current ailments and the eating disorder. A total of 49% had
      been weighed. INTERPRETATION: In order to be able to establish the best possible
      basis for a medical assessment, the GP should ask specifically about each symptom
      of an eating disorder.

PMID- 25387930
TI  - Detection of cerebrospinal fluid leakage with tinted chlorhexidine.

PMID- 25387931
TI  - [A woman in her 60s with persistent headache].

PMID- 25387932
TI  - [Markov modeling].

PMID- 25387933
TI  - [Art psychotherapy and eating disorders].

PMID- 25387934
TI  - Prevention of chemical violence in Syria.

PMID- 25387935
TI  - [International health and global Health--what's the difference?].

PMID- 25387948
TI  - Deep neck infections in cervical injection drug users.
AB  - OBJECTIVES/HYPOTHESIS: To characterize deep neck infections (DNI) in adult
      intravenous drug users (IDUs) who injected illicit substances to their neck, in
      comparison to DNI in non-IDUs. STUDY DESIGN: Retrospective, cohort study.
      METHODS: Data were retrieved from medical charts of adult DNI patients in a
      secondary hospital during 2000-2013. Clinical, radiologic, and microbial data
      were extracted and tabulated following categorization into 2 patient groups: IDUs
      and non-IDUs. RESULTS: Of the 136 patients identified with DNI, 20 (15%) were
      IDUs; of them 80% were males. IDUs were significantly younger than non-IDUs (mean
      age, 35 +/- 10 vs. 44 +/- 16 years, P = .01). All IDUs had multiple
      comorbidities. IDUs presented for medical examination and hospitalization later
      in the course of their disease, and the most common involved neck spaces were
      consistent with areas where cervical injections are commonly performed. Abscess
      formation was more common in IDUs than non-IDUs (16 [80%] vs. 79 [68%],
      respectively, P = .04). Despite later presentation of IDUs and their higher rate
      of comorbidities, laboratory data, microbiology cultures, and disease course were
      similar to non-IDUs. CONCLUSIONS: Although IDU and non-IDU differ in DNI
      presentation, both groups had good outcomes. DNI in IDUs frequently evolved into
      abscesses, and most were found in the anterior triangle deep to
      sternocleidomastoid (SCM), posterior triangle, and anterior triangle superficial
      to SCM, in concordance with the injection sites. LEVEL OF EVIDENCE: 4.

PMID- 25387947
TI  - Protein evolution of Toll-like receptors 4, 5 and 7 within Galloanserae birds.
AB  - BACKGROUND: Toll-like receptors (TLR) are essential activators of the innate part
      of the vertebrate immune system. In this study, we analysed the interspecific
      variability of three TLR (bacterial-sensing TLR4 and TLR5 and viral-sensing TLR7)
      within the Galloanserae bird clade, investigated their phylogeny, assessed their
      structural conservation and estimated site-specific selection pressures. RESULTS:
      Physiochemical properties varied according to the TLR analysed, mainly with
      regards to the surface electrostatic potential distribution. The predicted ligand
      binding features (mainly in TLR4 and TLR5) differed between the avian proteins
      and their fish and mammalian counterparts, but also varied within the
      Galloanserae birds. We identified 20 positively selected sites in the three TLR,
      among which several are topologically close to ligand-binding sites reported for
      mammalian and fish TLR. We described 26, 28 and 25 evolutionarily non
      conservative sites in TLR4, TLR5 and TLR7, respectively. Thirteen of these sites
      in TLR4, and ten in TLR5 were located in functionally relevant regions. The
      variability appears to be functionally more conserved for viral-sensing TLR7 than
      for the bacterial-sensing TLR. Amino-acid positions 268, 270, 343, 383, 444 and
      471 in TLR4 and 180, 183, 209, 216, 264, 342 and 379 in TLR5 are key candidates
      for further functional research. CONCLUSIONS: Host-pathogen co-evolution has a
      major effect on the features of host immune receptors. Our results suggest that
      avian and mammalian TLR may be differentially adapted to pathogen-derived ligand
      recognition. We have detected signatures of positive selection even within the
      Galloanserae lineage. To our knowledge, this is the first study to depict
      evolutionary pressures on Galloanserae TLR and to estimate the validity of
      current knowledge on TLR function (based on mammalian and chicken models) for non
      model species of this clade.

PMID- 25387949
TI  - The MESA heart failure risk score: can't we do more?

PMID- 25387950
TI  - White matter abnormalities associated with military PTSD in the context of blast
      TBI.
AB  - Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are
      common among recent military veterans and involve substantial symptom overlap,
      making clinical distinction and effective intervention difficult. Emerging
      evidence of cerebral white matter abnormalities associated with mTBI may provide
      a biological measure to inform diagnosis and treatment, but the potentially
      confounding effects between PTSD and mTBI have largely gone unexamined. We
      collected diffusion imaging data from 133 recently-deployed American service
      members who developed PTSD and/or sustained mTBI, or had neither condition.
      Effects of PTSD and mTBI on traditional tensor-based measures of cerebral white
      matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) were
      compared in anatomical regions of interest and individual voxels throughout the
      brain. Generalized FA (GFA), which allows for multiple fiber orientations per
      voxel, was also included to improve sensitivity in white matter areas containing
      crossing or diverging axon bundles. PTSD was consistently associated with high
      GFA in select brain regions, greater likelihood of regions and voxels with
      abnormally low MD, and a greater number of voxels with abnormally high FA, while
      mTBI was associated with fewer high MD regions. Overall, PTSD was associated with
      more restricted diffusion (low MD) and greater anisotropy (high GFA) in regions
      of crossing/diverging fibers poorly characterized by a single tensor (FA),
      suggesting that interstitial fibers may be involved. Contrary to earlier results
      in a sample without PTSD, mTBI was not associated with anisotropy abnormalities,
      perhaps indicating the cooccurrence of PTSD and mTBI requires special
      consideration with regard to structural brain connectivity.

PMID- 25387951
TI  - Radial head replacement with pyrocarbon prosthesis: early clinical results.
AB  - BACKGROUND: Comminuted radial head fractures are challenging to treat with open
      reduction and internal fixation. Radial head arthroplasty is a favourable
      technique for the treatment of complex radial head fractures. The purpose of this
      study was to evaluate the functional and radiological outcomes of radial head
      arthroplasty using modular pyrocarbon radial head prosthesis. METHODS: We
      retrospectively reviewed 21 consecutive patients requiring radial head
      arthroplasty for unreconstructible radial head fractures between July 2003 and
      July 2009. Patients completed a Short Form-36 (SF-36), the Disabilities of the
      Arm, Shoulder and Hand questionnaire, and the Mayo Elbow Performance Index.
      Patients were independently physically examined and their post-operative
      radiographs were reviewed. RESULTS: Twenty-one patients (nine males and 12
      females) were reviewed at a minimum of 12 months follow-up. The mean Disabilities
      of the Arm, Shoulder and Hand score was 10.8 (0-34.1), mean SF-36 physical score
      was 76.9 (35-96), mean SF-36 mental score was 83.8 (60-94), and their Mayo Elbow
      Performance Index score was 86.4 (70-100). Patients maintained 90% of their grip
      strength when compared with their uninjured arm and had 17.5 degrees  of fixed
      flexion in the affected arm. Radiologically, 14 cases had some degree of post
      traumatic osteoarthritis, 12 cases had evidence of heterotrophic ossification,
      five had some evidence of periprosthetic lucency and three patients were
      radiologically, but not functionally 'overstuffed'. CONCLUSION: Radial head
      arthroplasty with pyrocarbon radial head prosthesis is an acceptable option when
      treating unreconstructable radial head fractures yielding good functional and
      radiological outcomes.

PMID- 25387953
TI  - How would patent reform legislation in the United States impact the
      pharmaceutical industry?
AB  - The United States Congress is attempting to tackle a perceived problem with so
      called 'patent trolls' by introducing legislation directed at the particular
      traits attributable to these patent holders. Two of these proposed provisions
      involve fee-shifting and heightened pleading standards. The problem is that these
      legislative proposals are not narrowly tailored, but rather are blunt instruments
      that will likely impact all patent holders. This threat is particularly
      problematic for the pharmaceutical industry, where the proposed patent reform is
      likely to disrupt the delicate balance established for Hatch-Waxman-type
      litigation. 

PMID- 25387954
TI  - Sustainable endospore-based microreactor system for antioxidant capacity assay.
AB  - A novel endospore-based microbial method for "post-additional" antioxidant
      capacity assay was developed. The technique was based on oxidation and catalysis
      of the 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) by Bacillus
      subtilis 168 endospores in the presence of dissolved oxygen. Coat protein A
      (CotA), which belongs to the endospore coat, was expressed, purified, and
      assessed for its ability to oxidize ABTS into the ABTS(*+) radical cation. The
      wild-type endospore necessary for oxidizing ABTS into ABTS(*+) radical cation was
      confirmed by knocking out the cotA gene from B. subtilis 168 by homologous double
      exchange. Findings revealed that the catalytic activity of the endospores may be
      attributed to the presence of the CotA protein. The use of endospores instead of
      purified enzymes to prepare ABTS(*+) greatly reduced the assay cost and
      eliminated the need to purify and store of enzymes. The self-life of the radical
      cation was kept stable for at least 12 days without addition of a stabilizer and
      laccase inhibitor. This behavior enables the large-scale preparation of ABTS(*+).
      The antioxidant capacities of the individual antioxidants and fruit samples were
      easily quantified and compared using the proposed method. The developed technique
      can be further developed as a high-throughput screening technique for
      antioxidants. 

PMID- 25387952
TI  - p63-dependent and independent mechanisms of nectin-1 and nectin-4 regulation in
      the epidermis.
AB  - Nectins are immunoglobulin-like cell adhesion molecules mainly localized in
      adherens junctions. The transcription factor p63 is a master regulator of gene
      expression in stratified epithelia and controls several molecular processes. As
      mutations in the Pvrl1 and Pvrl4 genes encoding for nectins cause genetic
      disorders with phenotypes similar to p63-related syndromes, we investigated
      whether these proteins might be under p63 transcriptional control. Here, we show
      that in p63-null skin, Pvrl1 gene expression is strongly reduced, whereas Pvrl4
      expression is unaffected. In human and mouse primary keratinocytes p63 depletion
      leads to a specific downregulation of the Pvrl1 gene. Consistent with a direct
      regulation, chromatin immunoprecipitation experiments (ChIP) indicate that p63
      binds to two conserved intronic Pvrl1 enhancer regions. Ankyloblepharon
      ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant
      disorder, caused by mutations in p63 gene, mainly characterized by skin
      fragility. To test whether nectins may be affected in AEC syndrome, their
      expression was measured in keratinocytes obtained from patients with AEC or from
      a conditional mouse model for AEC syndrome. Pvrl1 expression was reduced in AEC
      keratinocytes, consistent with impaired p63 function. Surprisingly, Pvrl4
      expression was similarly affected, in parallel with decreased expression of the
      transcription factor Irf6. Consistent with the well-characterized role of Irf6 in
      keratinocyte differentiation and its strong downregulation in AEC syndrome, Irf6
      depletion caused reduced expression of Pvrl4 in wild-type keratinocytes. Taken
      together, our results indicate that Pvrl1 is a bona fide target gene of the
      transcription factor p63, whereas Pvrl4 regulation is linked to epidermal
      differentiation and is under Irf6 control. 

PMID- 25387955
TI  - Introduction to structural bioinformatics.
AB  - Structural Bioinformatics is one of the hot spots of interdisciplinary sciences
      and obtained amazing advances in recent years. The first chapter overviews the
      concept of structural bioinformatics, and briefly describe the contents of this
      book. The interdisciplinary corporations make it difficult to further divide
      structural bioinformatics, so the chapters in this book are roughly separated
      according to the different fields of their applications. That is, fundamental
      developments in methods of structural bioinformatics, tertiary structure
      prediction and folding mechanism analysis, the binding mechanism and the
      interactions between biological macromolecules and ligands, structure-based
      functional analysis of biological macromolecules, as well as the applications in
      drug design. 

PMID- 25387956
TI  - JVM: Java Visual Mapping tool for next generation sequencing read.
AB  - We developed a program JVM (Java Visual Mapping) for mapping next generation
      sequencing read to reference sequence. The program is implemented in Java and is
      designed to deal with millions of short read generated by sequence alignment
      using the Illumina sequencing technology. It employs seed index strategy and
      octal encoding operations for sequence alignments. JVM is useful for DNA-Seq, RNA
      Seq when dealing with single-end resequencing. JVM is a desktop application,
      which supports reads capacity from 1 MB to 10 GB.

PMID- 25387957
TI  - Advancement of polarizable force field and its use for molecular modeling and
      design.
AB  - The most important requirement of biomolecular modeling is to deal with
      electrostatic energies. The electrostatic polarizability is an important part of
      electrostatic interaction for simulation systems. However, AMBER, CHARMM, OPLS,
      GROMOS, MMFF force fields etc. used in the past mostly apply fixed atomic center
      point charge to describe electrostatic energies, and are not sufficient for
      considering the influence of the electrostatic polarization. The emergence of
      polarizable force fields has solved this problem. In recent years, quickly
      developed polarizable force fields have involved a lot of fields. The chapter
      relating to polarizable force fields spread over several aspects. Firstly, we
      reviewed the history of the classical force fields and compared with polarizable
      force fields to elucidate the advancements of polarizable force fields. Secondly,
      it is introduced that the application of polarizable force fields to small
      molecules and biological macromolecules simulation, including molecular design.
      Finally, a brief development trend and perspective is given on rapidly growing
      polarizable force fields. 

PMID- 25387958
TI  - Systematic methods for defining coarse-grained maps in large biomolecules.
AB  - Large biomolecules are involved in many important biological processes. It would
      be difficult to use large-scale atomistic molecular dynamics (MD) simulations to
      study the functional motions of these systems because of the computational
      expense. Therefore various coarse-grained (CG) approaches have attracted rapidly
      growing interest, which enable simulations of large biomolecules over longer
      effective timescales than all-atom MD simulations. The first issue in CG modeling
      is to construct CG maps from atomic structures. In this chapter, we review the
      recent development of a novel and systematic method for constructing CG
      representations of arbitrarily complex biomolecules, in order to preserve large
      scale and functionally relevant essential dynamics (ED) at the CG level. In this
      ED-CG scheme, the essential dynamics can be characterized by principal component
      analysis (PCA) on a structural ensemble, or elastic network model (ENM) of a
      single atomic structure. Validation and applications of the method cover various
      biological systems, such as multi-domain proteins, protein complexes, and even
      biomolecular machines. The results demonstrate that the ED-CG method may serve as
      a very useful tool for identifying functional dynamics of large biomolecules at
      the CG level. 

PMID- 25387959
TI  - Quantum calculation of protein NMR chemical shifts based on the automated
      fragmentation method.
AB  - The performance of quantum mechanical methods on the calculation of protein NMR
      chemical shifts is reviewed based on the recently developed automatic
      fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach. By using
      the Poisson-Boltzmann (PB) model and first solvation water molecules, the
      influence of solvent effect is also discussed. Benefiting from the fragmentation
      algorithm, the AF-QM/MM approach is computationally efficient, linear-scaling
      with a low pre-factor, and thus can be applied to routinely calculate the ab
      initio NMR chemical shifts for proteins of any size. The results calculated using
      Density Functional Theory (DFT) show that when the solvent effect is included,
      this method can accurately reproduce the experimental 1H NMR chemical shifts,
      while the 13C NMR chemical shifts are less affected by the solvent. However,
      although the inclusion of solvent effect shows significant improvement for 15N
      chemical shifts, the calculated values still have large deviations from the
      experimental observations. Our study further demonstrates that AF-QM/MM
      calculated results accurately reflect the dependence of 13C(alpha) NMR chemical
      shifts on the secondary structure of proteins, and the calculated 1H chemical
      shift can be utilized to discriminate the native structure of proteins from
      decoys.

PMID- 25387960
TI  - Applications of rare event dynamics on the free energy calculations for membrane
      protein systems.
AB  - Techniques of rare event dynamics were reviewed including the string methods,
      which will be implemented with the biochemical simulation packages. The existing
      methods were applied to study biological systems with relevance to drug design
      and drug metabolism. The rare event dynamics simulations were performed to
      understand the kinetic and thermodynamic free energy information on the drug
      binding sites in the M2 proton channel, and also the free energy of insertion and
      association of membrane proteins and membrane active peptides. Results give a
      theoretical framework to interpret and reconcile existing and often conflicting
      opinions. 

PMID- 25387961
TI  - Extended structure of rat islet amyloid polypeptide in solution.
AB  - The process of islet amyloid polypeptide (IAPP) formation and the prefibrillar
      oligomers are supposed to be one of the pathogenic agents causing pancreatic beta
      cell dysfunction. The human IAPP (hIAPP) aggregates easily and therefore, it is
      difficult to characterize its structural features by standard biophysical tools.
      The rat version of IAPP (rIAPP) that differs by six amino acids when compared
      with hIAPP, is not prone to aggregation and does not form amyloid fibrils.
      Similar to hIAPP it also demonstrates random-coiled nature in solution. The
      structural propensity of rIAPP has been studied as a hIAPP mimic in recent works.
      However, the overall shape of it in solution still remains elusive. Using small
      angle X-ray scattering (SAXS) measurements combined with nuclear magnetic
      resonance (NMR) and molecular dynamics simulations (MD) the solution structure of
      rIAPP was studied. An unambiguously extended structural model with a radius of
      gyration of 1.83 nm was determined from SAXS data. Consistent with previous
      studies, an overall random-coiled feature with residual helical propensity in the
      N-terminus was confirmed. Combined efforts are necessary to unambiguously resolve
      the structural features of intrinsic disordered proteins.

PMID- 25387962
TI  - Folding mechanisms of Trefoil Knot proteins studied by molecular dynamics
      simulations and Go-model.
AB  - Most proteins need to avoid the complex topologies when folding into the native
      structures, but some proteins with nontrivial topologies have been found in
      nature. Here we used protein unfolding simulations under high temperature and all
      atom Go-model to investigate the folding mechanisms for two trefoil knot
      proteins. Results show that, the contacts in beta-sheet are important to the
      formation of knot protein, and if these contacts disappeared, the knot protein
      would be easy to untie. In the Go-model simulations, the folding processes of the
      two knot proteins are similar. The compact structures of the two knot proteins
      with the native contacts in beta-sheet are formed in transition state, and the
      intermediate state has loose C-terminal. This model also reveals the detailed
      folding mechanisms for the two proteins. 

PMID- 25387963
TI  - Binding induced intrinsically disordered protein folding with molecular dynamics
      simulation.
AB  - Intrinsically disordered proteins lack stable tertiary and/or secondary
      structures under physiological conditions in vitro. Intrinsically disordered
      proteins undergo significant conformational transitions to well folded forms only
      on binding to partner. Molecular dynamics simulations are used to research the
      mechanism of folding for intrinsically disordered protein upon partner binding.
      Room-temperature MD simulations suggest that the intrinsically disordered
      proteins have nonspecific and specific interactions with the partner. Kinetic
      analysis of high-temperature MD simulations shows that bound and apo-states
      unfold via a two-state process, respectively. Phi-value analysis can identify the
      key residues of intrinsically disordered proteins. Kolmogorov-Smirnov (KS) P test
      analysis illustrates that the specific recognition between intrinsically
      disordered protein and partner might follow induced-fit mechanism. Furthermore,
      these methods can be widely used for the research of the binding induced folding
      for intrinsically disordered proteins. 

PMID- 25387964
TI  - Theoretical studies on the folding mechanisms for different DNA G-quadruplexes.
AB  - The G-quadruplex DNA formed by the stack of guanines in human telomere sequence
      is a promising anticancer target. In this study we used the energy landscape
      theory to elucidate the folding mechanisms for the thrombin aptamer, Form 1 and
      Form 3 G-quadruplexes. The three G-quadruplexes were simulated with all-atom Go
      model. Results show that, the three G-quadruplexes fold through a two-state
      mechanism. In the initial stage of the folding process, the compact structures
      are formed. The G-quadruplexes need to form G-triplex structures on the basis of
      the compact structures before folding to the native states. The folding free
      energy barrier of Form 3 G-quadruplex is higher than thrombin aptamer and Form 1,
      which shows that the structure of Form 3 G-quadruplex has more stability than the
      other two G-quadruplexes. 

PMID- 25387965
TI  - RNA folding: structure prediction, folding kinetics and ion electrostatics.
AB  - Beyond the "traditional" functions such as gene storage, transport and protein
      synthesis, recent discoveries reveal that RNAs have important "new" biological
      functions including the RNA silence and gene regulation of riboswitch. Such
      functions of noncoding RNAs are strongly coupled to the RNA structures and proper
      structure change, which naturally leads to the RNA folding problem including
      structure prediction and folding kinetics. Due to the polyanionic nature of RNAs,
      RNA folding structure, stability and kinetics are strongly coupled to the ion
      condition of solution. The main focus of this chapter is to review the recent
      progress in the three major aspects in RNA folding problem: structure prediction,
      folding kinetics and ion electrostatics. This chapter will introduce both the
      recent experimental and theoretical progress, while emphasize the theoretical
      modelling on the three aspects in RNA folding. 

PMID- 25387966
TI  - Binding modes and interaction mechanism between different base pairs and
      methylene blue trihydrate: a quantum mechanics study.
AB  - Different quantum mechanic methods have been evaluated for the calculation of
      binding modes and interactions between intercalators with different DNA base
      pairs by comparing with the results of MP2, which is very expensive, indicating
      that WB97XD method under 6-311+G* basis set is able to efficiently reproduce MP2
      results. We discovered that the methylene blue trihydrate intercalated into the
      DNA base pairs, and DNA intercalation increased the distance between DNA base
      pairs, depending on the types of DNA bases. According to the binding energy
      results, it was found that the intercalation of methylene blue trihydrate into AA
      TT base pair was more favorable in the orientation of nitrogen than other
      directions and intercalation, and the electric charge was transferred from
      methylene blue trihydrate to the AA-TT base pair. The analysis of change in the
      charge density shows that changes often take place in the heavy atom in the
      middle of the system which the charge density changes most remarkable. 

PMID- 25387967
TI  - Drug inhibition and proton conduction mechanisms of the influenza a M2 proton
      channel.
AB  - The influenza A virus matrix protein 2 (M2 protein) is a pH-regulated proton
      channel embedded in the viral membrane. Inhibition of the M2 proton channel has
      been used to treat influenza infections for decades due to the crucial role of
      this protein in viral infection and replication. However, the widely-used M2
      inhibitors, amantadine and rimantadine, have gradually lost their efficiencies
      because of naturally-occurring drug resistant mutations. Therefore, investigation
      of the structure and function of the M2 proton channel will not only increase our
      understanding of this important biological system, but also lead to the design of
      novel and effective anti-influenza drugs. Despite the simplicity of the M2
      molecular structure, the M2 channel is highly flexible and there have been
      controversies and arguments regarding the channel inhibition mechanism and the
      proton conduction mechanism. In this book chapter, we will first carefully review
      the experimental and computational studies of the two possible drug binding sites
      on the M2 protein and explain the mechanisms regarding how inhibitors prevent
      proton conduction. Then, we will summarize our recent molecular dynamics
      simulations of the drug-resistant mutant channels and propose mechanisms for drug
      resistance. Finally, we will discuss two existing proton conduction mechanisms
      and talk about the remaining questions regarding the proton-relay process through
      the channel. The studies reviewed here demonstrate how molecular modeling and
      simulations have complemented experimental work and helped us understand the M2
      channel structure and function. 

PMID- 25387968
TI  - Exploring the ligand-protein networks in traditional chinese medicine: current
      databases, methods and applications.
AB  - While the concept of "single component-single target" in drug discovery seems to
      have come to an end, "Multi-component-multi-target" is considered to be another
      promising way out in this field. The Traditional Chinese Medicine (TCM), which
      has thousands of years' clinical application among China and other Asian
      countries, is the pioneer of the "Multi-component-multi-target" and network
      pharmacology. Hundreds of different components in a TCM prescription can cure the
      diseases or relieve the patients by modulating the network of potential
      therapeutic targets. Although there is no doubt of the efficacy, it is difficult
      to elucidate convincing underlying mechanism of TCM due to its complex
      composition and unclear pharmacology. Without thorough investigation of its
      potential targets and side effects, TCM is not able to generate large-scale
      medicinal benefits, especially in the days when scientific reductionism and
      quantification are dominant. The use of ligand-protein networks has been gaining
      significant value in the history of drug discovery while its application in TCM
      is still in its early stage. This article firstly surveys TCM databases for
      virtual screening that have been greatly expanded in size and data diversity in
      recent years. On that basis, different screening methods and strategies for
      identifying active ingredients and targets of TCM are outlined based on the
      amount of network information available, both on sides of ligand bioactivity and
      the protein structures. Furthermore, applications of successful in silico target
      identification attempts are discussed in details along with experiments in
      exploring the ligand-protein networks of TCM. Finally, it will be concluded that
      the prospective application of ligand-protein networks can be used not only to
      predict protein targets of a small molecule, but also to explore the mode of
      action of TCM. 

PMID- 25387969
TI  - Evolutionary optimization of transcription factor binding motif detection.
AB  - All the cell types are under strict control of how their genes are transcribed
      into expressed transcripts by the temporally dynamic orchestration of the
      transcription factor binding activities. Given a set of known binding sites (BSs)
      of a given transcription factor (TF), computational TFBS screening technique
      represents a cost efficient and large scale strategy to complement the
      experimental ones. There are two major classes of computational TFBS prediction
      algorithms based on the tertiary and primary structures, respectively. A tertiary
      structure based algorithm tries to calculate the binding affinity between a query
      DNA fragment and the tertiary structure of the given TF. Due to the limited
      number of available TF tertiary structures, primary structure based TFBS
      prediction algorithm is a necessary complementary technique for large scale TFBS
      screening. This study proposes a novel evolutionary algorithm to randomly mutate
      the weights of different positions in the binding motif of a TF, so that the
      overall TFBS prediction accuracy is optimized. The comparison with the most
      widely used algorithm, Position Weight Matrix (PWM), suggests that our algorithm
      performs better or the same level in all the performance measurements, including
      sensitivity, specificity, accuracy and Matthews correlation coefficient. Our data
      also suggests that it is necessary to remove the widely used assumption of
      independence between motif positions. The supplementary material may be found at:
      http://www.healthinformaticslab.org/supp/ . 

PMID- 25387970
TI  - Prediction of serine/threonine phosphorylation sites in bacteria proteins.
AB  - As a critical post-translational modification, phosphorylation plays important
      roles in regulating various biological processes, while recent studies suggest
      that phosphorylation in bacteria is also critical for functional signaling
      transduction. Since identification of phosphorylation substrates and sites is
      fundamental for understanding the phosphorylation mediated regulatory mechanism,
      a number of studies have been contributed to this area. Since experimental
      identification of phosphorylation sites is time-consuming and labor-intensive,
      computational predictions attract much attention for its convenience to provide
      helpful information. However, although there are a large number of computational
      studies in eukaryotes, predictions in bacteria are still rare. In this study, we
      present a new predictor of cPhosBac to predict phosphorylation serine/threonine
      in bacteria proteins. The predictor is developed with CKSAAP algorithm, which was
      combined with motif length selection to optimize the prediction, which achieves
      promising performance. The online service of cPhosBac is available at:
      http://netalign.ustc.edu.cn/cphosbac/ . 

PMID- 25387971
TI  - Bioinformatics tools for discovery and functional analysis of single nucleotide
      polymorphisms.
AB  - With the high speed DNA sequencing of genome, databases of genome data continue
      to grow, and the understanding of genetic variation between individuals grows as
      well. Single nucleotide polymorphisms (SNPs), a main type of genetic variation,
      are increasingly important resource for understanding the structure and function
      of the human genome and become a valuable resource for investigating the genetic
      basis of disease. During the past years, in addition to experimental approaches
      to characterize specific variants, intense bioinformatics techniques were applied
      to understand effects of these genetic changes. In the genetics studies, one
      intends to understand the molecular basis of disease, and computational methods
      are becoming increasingly important for SNPs selection, prediction and
      understanding the downstream effects of genetic variation. The review provides
      systematic information on the available resources and methods for SNPs discovery
      and analysis. We also report some new results on DNA sequence-based prediction of
      SNPs in human cytochrome P450, which serves as an example of computational
      methods to predict and discovery SNPs. Additionally, annotation and prediction of
      functional SNPs, as well as a comprehensive list of existing tools and online
      recourses, are reviewed and described. 

PMID- 25387972
TI  - An application of QM/MM simulation: the second protonation of cytochrome P450.
AB  - The multiscale model strategy, hybrid quantum mechanics and molecular mechanics
      (QM/MM), has become more and more prevalent in the theoretical study of enzymatic
      reactions. It combines both the efficiency of the Newtonian molecular
      calculations and the accuracy of the quantum mechanical methods. Simulation using
      QM/MM multiscale model may be one of the most promising approaches that could
      further narrow the gap between the theoretical models and the real problems. It
      is capable of dealing with not only the conformational changes of
      biomacromolecules, but also the catalytic reactions. Herein, we reviewed some of
      our recent work to demonstrate the application of the QM/MM simulations in
      exploring the enzymatic reactions. 

PMID- 25387973
TI  - Recent progress on structural bioinformatics research of cytochrome P450 and its
      impact on drug discovery.
AB  - Cytochrome P450 is predominantly responsible for human drug metabolism, which is
      of critical importance for drug discovery and development. Structural
      bioinformatics focuses on analysis and prediction of three-dimentional structure
      of biological macromolecules and elucidation of structure-function relationship
      as well as identification of important binding interactions. Rapid advancement of
      structural bioinformatics has been made over the last decade. With more
      information available for CYP structures, the methods of structural
      bioinformatics may be used in the CYP field. In this review, we demonstrate three
      previous studies on CYP using the methods of structural bioinformatics, including
      the investigation of reasons for decrease of enzymatic activity of CYP1A2 caused
      by a peripheral mutation, the construction of a pharmacophore model specific to
      active site of CYP1A2 and the prediction of the functional consequences of single
      residue mutation in CYP. By illustrating these studies we attempt to show the
      potential role of structural bioinformatics in CYP research and help better
      understanding the importance of structural bioinformatics in drug designing. 

PMID- 25387974
TI  - Human cytochrome P450 and personalized medicine.
AB  - Personalized medicine has become a hot topic ascribed to the development of Human
      Genome Project. And currently, bioinformatics methodology plays an essential role
      in personal drug design. Here in this review we mainly focused on the basic
      introduction of the SNPs of human drug metabolic enzymes and their relationships
      with personalized medicine. Some common bioinformatics analysis methods and
      latest progresses and applications in personal drug design have also been
      discussed. Thus bioinformatics studies on SNPs of human CYP450 genes will
      contribute to indicate the most possible genes that are associated with human
      diseases and relevant therapeutic targets, identify and predict the drug efficacy
      and adverse drug response, investigate individual gene specific properties and
      then provide personalized and optimal clinic therapies. 

PMID- 25387975
TI  - The alpha7 nAChR selective agonists as drug candidates for Alzheimer's disease.
AB  - The nicotinic acetylcholine receptors (nAChRs) are ion channels distribute in the
      central or peripheral nervous system. They are receptors of the neurotransmitter
      acetylcholine and activation of them by agonists mediates synaptic transmission
      in the neuron and muscle contraction in the neuromuscular junction. Current
      studies reveal relationship between the nAChRs and the learning and memory as
      well as cognation deficit in various neurological disorders such as Alzheimer's
      disease, Parkinson's disease, schizophrenia and drug addiction. There are various
      subtypes in the nAChR family and the alpha7 nAChR is one of the most abundant
      subtypes in the brain. The alpha7 nAChR is significantly reduced in the patients
      of Alzheimer's disease and is believed to interact with the Abeta amyloid. Abeta
      amyloid is co-localized with alpha7 nAChR in the senile plaque and interaction
      between them induces neuron apoptosis and reduction of the alpha7 nAChR
      expression. Treatment with alpha7 agonist in vivo shows its neuron protective and
      procognation properties and significantly improves the learning and memory
      ability of the animal models. Therefore, the alpha7 nAChR agonists are excellent
      drug candidates for Alzheimer's disease and we summarized here the current
      agonists that have selectivity of the alpha7 nAChR over the other nAChR,
      introduced recent molecular modeling works trying to explain the molecular
      mechanism of their selectivity and described the design of novel allosteric
      modulators in our lab. 

PMID- 25387976
TI  - Bayesian analysis of complex interacting mutations in HIV drug resistance and
      cross-resistance.
AB  - A successful treatment of AIDS world-wide is severely hindered by the HIV virus'
      drug resistance capability resulting from complicated mutation patterns of viral
      proteins. Such a system of mutations enables the virus to survive and reproduce
      despite the presence of various antiretroviral drugs by disrupting their binding
      capability. Although these interacting mutation patterns are extremely difficult
      to efficiently uncover and interpret, they contribute valuable information to
      personalized therapeutic regimen design. The use of Bayesian statistical modeling
      provides an unprecedented opportunity in the field of anti-HIV therapy to
      understand detailed interaction structures of drug resistant mutations. Multiple
      Bayesian models equipped with Markov Chain Monte Carlo (MCMC) methods have been
      recently proposed in this field (Zhang et al. in PNAS 107:1321, 2010 [1]; Zhang
      et al. in J Proteome Sci Comput Biol 1:2, 2012 [2]; Svicher et al. in Antiviral
      Res 93(1):86-93, 2012 [3]; Svicher et al. in Antiviral Therapy 16(7):1035-1045,
      2011 [4]; Svicher et al. in Antiviral Ther 16(4):A14-A14, 2011 [5]; Svicher et
      al. in Antiviral Ther 16(4):A85-A85, 2011 [6]; Alteri et al. in Signature
      mutations in V3 and bridging sheet domain of HIV-1 gp120 HIV-1 are specifically
      associated with dual tropism and modulate the interaction with CCR5 N-Terminus,
      2011 [7]). Probabilistically modeling mutations in the HIV-1 protease or reverse
      transcriptase (RT) isolated from drug-treated patients provides a powerful
      statistical procedure that first detects mutation combinations associated with
      single or multiple-drug resistance, and then infers detailed dependence
      structures among the interacting mutations in viral proteins (Zhang et al. in
      PNAS 107:1321, 2010 [1]; Zhang et al. in J Proteome Sci Comput Biol 1:2, 2012
      [2]). Combined with molecular dynamics simulations and free energy calculations,
      Bayesian analysis predictions help to uncover genetic and structural mechanisms
      in the HIV treatment resistance. Results obtained with such stochastic methods
      pave the way not only for optimization of the use for existing HIV drugs, but
      also for the development of the new more efficient antiretroviral medicines. In
      this chapter we survey current challenges in the bioinformatics of anti-HIV
      therapy, and outline how recently emerged Bayesian methods can help with the
      clinical management of HIV-1 infection. We will provide a rigorous review of the
      Bayesian variable partition model and the recursive model selection procedure
      based on probability theory and mathematical data analysis techniques while
      highlighting real applications in HIV and HBV studies including HIV drug
      resistance (Zhang et al. in PNAS 107:1321, 2010 [1]), cross-resistance (Zhang et
      al. in J Proteome Sci Comput Biol 1:2, 2012 [2]), HIV coreceptor usage (Svicher
      et al. in Antiviral Therapy 16(7):1035-1045, 2011 [4]; Svicher et al. in
      Antiviral Ther 16(4):A14-A14, 2011 [5]; Alteri et al. in Signature mutations in
      V3 and bridging sheet domain of HIV-1 gp120 HIV-1 are specifically associated
      with dual tropism and modulate the interaction with CCR5 N-Terminus, 2011 [7]),
      and occult HBV infection (Svicher et al. in Antiviral Res 93(1):86-93, 2012 [3];
      Svicher et al. in Antiviral Ther 16(4):A85-A85, 2011 [6]). 

PMID- 25387977
TI  - Respiratory sinus arrhythmia in young men and women at different chest wall
      configurations.
AB  - Respiratory sinus arrhythmia (RSA) is an acceleration of heart rate during
      inspiration and deceleration with expiration. We asked whether or not in humans
      some of the volume-related information necessary for RSA originated from the
      chest wall. Men and women, 19-20 years old, were breathing supine. Rib cage and
      abdomen displacement provided an index of tidal volume (VT) and RSA was computed
      breath-by-breath from the peak and trough of instantaneous heart rate. First,
      measurements were taken during breathing at rest (protocol a, 129 male and 164
      female). Then, in subgroups of the original subject population, measurements were
      collected for the first five breaths immediately following a brief breath-hold
      period (protocol b), predominantly with the rib cage or predominantly with the
      abdomen (protocol c), above functional residual capacity or below it (protocol
      d). As long as VT was constant, severe chest wall distortion (protocol c) did not
      modify RSA. A drop in absolute lung volume (protocol d) or an increase in VT
      (protocol b) respectively decreased and increased RSA. The results, globally
      taken, are compatible with the notion that in humans changes in lung volume are
      detected by lung mechanoreceptors, whereas chest wall reflexes play no role in
      RSA. No difference in RSA emerged between genders during resting breathing or
      modest breath-hold hyperventilation. 

PMID- 25387978
TI  - [Children with hyperthyroidism due to elevated hCG levels].
AB  - We describe two children with hyperthyroidism secondary to elevated hCG levels:
      one patient with gestational trophoblastic disease and one patient with
      choriocarcinoma. hCG resembles other glycoproteins that can lead to
      hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking
      effect, hCG can induce high oestradiol levels, resulting in stormy pubertal
      development. False negative hCG tests due to the high-dose hook effect may
      complicate the diagnostic process. In patients with antibody-negative
      thyrotoxicosis, the diagnosis of hCG-induced hyperthyroidism must be considered. 

PMID- 25387979
TI  - [Thalassaemia diagnostics].
AB  - The thalassaemias are characterised by quantitative aberrations in the production
      of the globin chains that make up haemoglobin, and are a subgroup of the
      haemoglobinopathies. In this LabQuiz we show how thalassaemia carrier status can
      be indicated in the results of regular laboratory tests, and discuss the
      laboratory diagnostics that can confirm or rule out thalassaemia. In these two
      cases we will present a man of Moroccan descent, and two brothers of Filipino
      descent, all with anaemia and microcytosis. We show it is possible to
      differentiate between iron-deficiency anaemia and thalassaemia carrier status on
      the basis of a complete blood count and measurement of ferritin levels, and which
      laboratory diagnostics can be subsequently performed in order to confirm a
      suspicion of thalassaemia. The background section discusses the properties and
      pitfalls of routine laboratory diagnostics for the thalassaemias, and
      thalassaemia diagnostics in the Dutch newborn screening programme.

PMID- 25387980
TI  - [Sexuality and contraception in young people with mild intellectual disability; a
      qualitative study on the basis of 28 interviews].
AB  - OBJECTIVE: To investigate how doctors can improve the advice and education about
      sexuality and contraception given to young people with mild intellectual
      disability (IQ :50-70). DESIGN: Semi-structured interviews. METHOD: Young people
      attending special needs secondary schools (IQ: 50-70) were interviewed. Pupils
      with a known history of sexual abuse were excluded. RESULTS: A total of 17 of the
      57 potential candidates were excluded. Of the remaining 40 pupils, 28 agreed to
      take part (13 male; age range: 15-18 years, average IQ: 58). Of the 28
      participants, 19 had been in a relationship, 5 had experience with sexual
      intercourse and 11 used contraception. Just as in other studies, the participants
      seemed to have less knowledge, and less experience than young people of their age
      without a disability, but did show interest. They were at increased risk because
      of inappropriate use of contraception and had limited social resilience. Only
      knowledge about the pill and condoms was fair to good. Interest and knowledge
      seemed greater in those young people in a relationship. Poor verbal skills
      hampered their understanding of the questions asked and of the information
      offered, and limited their ability to express feelings and opinions. Those young
      people in a relationship wanted to choose their own form of contraception.
      CONCLUSION: In this group of vulnerable young people, provision of sexual
      education by the doctor at the right moment using simple language and repetition,
      can contribute to the timely and safe use of contraceptives.Conflict of interest
      and financial support: none declared.

PMID- 25387981
TI  - [Involuntary admission to psychiatric care of people with mild intellectual
      disability: missed chances in the Dutch Care and Coercion Act].
AB  - The aim of the Dutch Care and Coercion Act (Wet Zorg en Dwang) is to improve the
      legal position of people with an intellectual disability in cases of involuntary
      admission to psychiatric care. The present law, the Dutch Psychiatric Act (Wet
      BOPZ), only offers legal protection to clients who are admitted involuntarily to
      specific institutions. The Care and Coercion Act will lead to significant changes
      in the care of people with an intellectual disability and a much larger group of
      clients with an intellectual disability will fall under the range of this Act.
      Limitations to freedom - referred to as 'involuntary admission' within the new
      law - must meet the same criteria for each client. The legislator, however, seems
      to have paid little attention to those clients with a mild intellectual
      disability.

PMID- 25387982
TI  - [Concentration problem or epilepsy? Sudden changes in behaviour in adolescents].
AB  - Sudden changes in behaviour and concentration problems can be caused by non
      convulsive status epilepticus. This generalised form of epilepsy can be easily
      missed as a diagnosis. In this case report series we describe three adolescent
      boys (13, 14 and 17 years old respectively) presenting with behavioural
      disturbances caused by idiopathic non-convulsive status epilepticus. The
      diagnosis was confirmed by electroencephalography (EEG). The medical history
      mentioned previous episodes of changes in behaviour in all patients. The 14-year
      old boy was diagnosed with attention deficit hyperactivity disorder (ADHD). It is
      questionable whether this diagnosis was justified, or whether his behavioural
      problems were caused by non-convulsive epileptic seizures. Non-convulsive status
      epilepticus is characterised by diminished cognitive functioning in an otherwise
      reactive patient. Testing of memory and other cognitive functions is essential
      for diagnosis. All children with behavioural problems should undergo a thorough
      neurological assessment by a paediatrician or neurologist in order to recognise
      non-convulsive epilepsy. 

PMID- 25387983
TI  - [Eosinophilic otitis media].
AB  - BACKGROUND: Eosinophilic otitis media (EOM) is a rare middle ear disease that may
      closely resemble therapy-resistant otitis media with effusion (OME). The
      diagnosis is made if eosinophil-rich fluid is present with two or more of the
      following minor criteria: (a) history of nasal polyps or, (b) bronchial asthma,
      with (c) viscous fluid in the middle-ear, or (d) conventional otitis media
      treatment has no effect. CASE DESCRIPTION: A 70-year-old male with a history of
      the ASA triad (bronchial asthma, nasal/ethmoidal polyposis and aspirin
      intolerance) presented with progressive mixed hearing loss. Otoscopy showed
      bilateral otitis media with effusion (OME). Conventional treatment of this had no
      effect. Myringotomy resulted in the evacuation of highly viscous middle-ear
      effusion containing abundant eosinophils. After treatment with oral
      corticosteroids his symptoms improved considerably. Following later optimisation
      of his asthma treatment, corticosteroid treatment was stopped and his hearing
      remained stable. CONCLUSION: The adequate recognition and treatment of EOM will
      result in the prevention of permanent hearing loss.

PMID- 25387984
TI  - Use of surface plasmons for manipulation of organic molecule  quasiparticles and
      optical properties.
AB  - Our recently proposed theoretical formulation based on Bethe-Salpeter G(0)W(0)
      methodology is applied here to explore the quasiparticle and optical spectra of
      anthracene (C(14)H10) placed close to a metallic surface. Special attention is
      paid to explore how the energy shift and decay width of the low-lying anthracene
      bright excitons p, alpha and beta depend on the type of the adjacent surface
      (described by the Wigner Seits radius r(s)) and the separation from the surface.
      It is shown that p and alpha excitons weakly interact with surface excitations,
      but for r(s) ~ 3 the intensive beta exciton hybridizes with surface plasmon
      considerably, resulting in its splitting into two optically active modes. The
      beta exciton decays extraordinarily fast (Gamma ~ 200 meV) to the electron-hole
      excitations in the metallic surface even for non-contact separations (z(0) ~ 12
      a.u.). For r(s) > 5 the beta exciton becomes infinitely sharp (Gamma ~ 0) and no
      longer interacts with the surface plasmon. Moreover, it is shown that HOMO and
      LUMO states near a metallic surface behave as statically screened rigid orbitals,
      with the result that the simple image theory arguments are sufficient to explain
      the HOMO-LUMO gap shift. Finally, it is demonstrated that the HOMO-LUMO gap shift
      dominantly depends on the position of the effective image plane z(im) of the
      adjacent surface.

PMID- 25387985
TI  - Theoretical chemical kinetic study of the H-atom abstraction reactions from
      aldehydes and acids by H atoms and OH, HO2, and CH3 radicals.
AB  - We have performed a systematic, theoretical chemical kinetic investigation of H
      atom abstraction by H atoms and OH, HO2, and CH3 radicals from aldehydes
      (methanal, ethanal, propanal, and isobutanal) and acids (methanoic acid, ethanoic
      acid, propanoic acid, and isobutanoic acid). The geometry optimizations and
      frequencies of all of the species in the reaction mechanisms of the title
      reactions were calculated using the MP2 method and the 6-311G(d,p) basis set. The
      one-dimensional hindered rotor treatment for reactants and transition states and
      the intrinsic reaction coordinate calculations were also determined at the MP2/6
      311G(d,p) level of theory. For the reactions of methanal and methanoic acid with
      H atoms and OH, HO2, and CH3 radicals, the calculated relative electronic
      energies were obtained with the CCSD(T)/cc-pVXZ (where X = D, T, and Q) method
      and were extrapolated to the complete basis set limit. The electronic energies
      obtained with the CCSD(T)/cc-pVTZ method were benchmarked against the CCSD(T)/CBS
      energies and were found to be within 1 kcal mol(-1) of one another. Thus, the
      energies calculated using the less expensive CCSD(T)/cc-pVTZ method were used in
      all of the reaction mechanisms and in calculating our high-pressure limit rate
      constants for the title reactions. Rate constants were calculated using
      conventional transition state theory with an asymmetric Eckart tunneling
      correction, as implemented in Variflex. Herein, we report the individual and
      average rate constants, on a per H atom basis, and total rate constants in the
      temperature range 500-2000 K. We have compared some of our rate constant results
      to available experimental and theoretical data, and our results are generally in
      good agreement. 

PMID- 25387986
TI  - Reviewing the topic of migration and health as a new national health target for
      Germany.
AB  - OBJECTIVES: To review migration and health as a potential new national health
      target for Germany. METHODS: The theme was evaluated along 13 standardized
      criteria preset by the Health Targets Network. For each of the criteria an expert
      opinion based on an extensive (but nonsystematic) review of literature is
      presented. RESULTS: Migrants differ in many health-related aspects from the
      majority population in Germany. Despite having some health advantages, their
      health status, on average, is lower than that of non-migrants. They also
      experience barriers in health care and cannot participate in the society on equal
      terms with the majority population. Different measures to improve the health
      situation of migrants are available, but their current implementation in the
      health system is limited in several ways. Present data on the health of migrants
      is inadequate and limits migrant-sensitive health reporting. CONCLUSION: The
      evaluation of potential health targets based on standardized criteria is a
      valuable tool for health policy formulation. The present documentation can assist
      other countries in evaluating migration and health as a national health target.
      It may also contribute to similar activities at the European level.

PMID- 25387987
TI  - Predicting early blast transformation in chronic-phase chronic myeloid leukemia:
      is immunophenotyping the missing link?
AB  - BACKGROUND: Flow cytometry (FC) is a commonly requested test in the workup of
      leukocytosis in community practices. The role of FC in chronic-phase chronic
      myeloid leukemia (CP-CML) is unknown. We hypothesized that finding aberrant cells
      with FC in CP-CML may predict early blast-phase (BP) transformation. METHODS:
      Results for FC performed at the time of diagnosis for adult and pediatric
      patients with CP-CML who were referred to our institution were reviewed, and they
      were correlated with outcomes. RESULTS: FC was performed at the time of diagnosis
      for 110 of 233 patients (47%) with CP-CML. Aberrant populations, representing a
      median of 2% (range, 0.3%-15%), were detected with FC in 30% of patients (33 of
      110): 2 of these 33 patients expressed lymphoid markers, and 31 expressed
      aberrant myeloid markers. Patients received imatinib (85%), dasatinib (12%), or
      nilotinib (3%) as their first-line treatment. With a median follow-up of 43
      months (range, 2-113 months), chronic myeloid leukemia transformed to BP in 5 of
      the 33 patients. The 2 patients with lymphoid markers and the 3 of 31 patients
      with aberrant myeloid markers experienced a transformation to lymphoid BP at a
      median of 11 months (range, 4-72 months) after the initiation of tyrosine kinase
      inhibitor therapy. Although both cases with detectable lymphoid markers rapidly
      progressed to lymphoid BP, the positive predictive value of BP transformation by
      the detection of myeloid aberrant cells with FC was only 10% (3 of 31).
      CONCLUSIONS: In contrast to aberrant myeloid markers, the detection of lymphoid
      markers by FC at the time of the diagnosis of CP-CML appears to be associated
      with early progression to lymphoid BP.

PMID- 25387988
TI  - A triple-function zwitterion for preparing water compatible diclofenac imprinted
      polymers.
AB  - A novel zwitterion acting as both a functional monomer and a crosslinker with the
      protein-resistant ability concomitantly was synthesized for preparing water
      compatible diclofenac imprinted polymers. This new imprinted polymer showed high
      imprinting efficiency for template and strong anti-protein adsorption in aqueous
      medium. 

PMID- 25387989
TI  - The nail dermis: from microanatomy to constitutive modelling.
AB  - AIMS: The nail mesenchyme, as ligamentous connective tissue, is classically
      described as a single compartment. Some authors have even suggested the concept
      of the nail as a musculoskeletal appendage. Recent studies conducted on
      supernumerary digits surgically removed for polydactyly or on the developing nail
      organ have introduced into the literature a new concept: the onychodermis and its
      onychofibroblasts that are CD10-positive/CD34-negative. The aim of this study was
      to explore the nail mesenchyme more comprehensively. METHODS AND RESULTS: A
      series of 10 normal adult nail units were examined with a combination of
      morphological and immunohistochemical analysis. This study demonstrates that the
      nail mesenchyme has two distinct compartments, with a complex microanatomy of
      matrical dermis and its hypoderm. The matrical dermis is a relatively independent
      substructure, and comprises two parts: a thin papillary dermis, and a relatively
      thick reticular dermis. The matrical hypoderm corresponds to a cushion-like layer
      of adipose tissue, which distally intermingles with an area of loose connective
      tissue. The nail bed dermis comprises a single, relatively homogeneous
      compartment. CONCLUSION: The matrical nail mesenchyme is a modified dermis. The
      concept of onychodermis is not applicable in the normal adult nail.
      Underrecognized non-pathological structures may pose diagnostic problems. The
      chameleon matrical hypoderm is one such structure.

PMID- 25387990
TI  - Electrically tunable optical polarization rotation on a silicon chip using
      Berry's phase.
AB  - The continued convergence of electronics and photonics on the chip scale can
      benefit from the voltage control of optical polarization for applications in
      communications, signal processing and sensing. It is challenging, however, to
      electrically manipulate the polarization state of light in planar optical
      waveguides. Here we introduce out-of-plane optical waveguides, allowing access to
      Berry's phase, a quantum-mechanical phenomenon of purely topological origin. As a
      result, electrically tunable optical polarization rotation on the chip scale is
      achieved. Devices fabricated in the silicon-on-insulator material platform are
      not limited to a single static polarization state. Rather, they can exhibit
      dynamic tuning of polarization from the fundamental transverse electric mode to
      the fundamental transverse magnetic mode. Electrical tuning of optical
      polarization over a 19 dB range of polarization extinction ratio is demonstrated
      with less than 1 dB of conversion loss at infrared wavelengths. Compact system
      architectures involving dynamic control of optical polarization in integrated
      circuits are envisioned.

PMID- 25387991
TI  - Phenotype analysis of Polish patients with mandibulofacial dysostosis type Guion
      Almeida associated with esophageal atresia and choanal atresia caused by EFTUD2
      gene mutations.
AB  - We present the phenotype of three unrelated Polish patients with MFD type Guion
      Almeida confirmed by EFTUD2 mutations. In all of our patients, dysmorphic
      craniofacial features, microcephaly, thumb abnormalities, psychomotor and speech
      delay were described. In addition, among other major defects, esophageal atresia
      (EA) in one patient and choanal atresia in two of them were present. Three
      different mutations in EFTUD2 gene were found in presented patients. Our
      observations confirm the clinical heterogeneity of mandibulofacial dysostosis
      type Guion-Almeida and its connection with major congenital defects such as
      esophageal atresia and choanal atresia. 

PMID- 25387992
TI  - Hyperbaric oxygen therapy for acute ischaemic stroke.
AB  - Background Most cases of stroke are caused by impairment of blood flow to the
      brain (ischaemia), which results in a reduction in available oxygen and
      subsequent cell death. It has been postulated that hyperbaric oxygen therapy
      (HBOT) may reduce the volume of brain that will die by greatly increasing
      available oxygen, and it may further improve outcomes by reducing brain swelling.
      Some centres are using HBOT routinely to treat people with stroke. This is an
      update of a Cochrane Review first published in 2005.Objectives To assess the
      effectiveness and safety of adjunctive HBOT in the treatment of people with acute
      ischaemic stroke.Search methods We searched the Cochrane Stroke Group Trials
      Register (last searched April 2014), the Cochrane Central Register of Controlled
      Trials(CENTRAL) (April 2014), MEDLINE (1966 to April 2014), EMBASE (1980 to April
      2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL)
      (1982 to April 2014), the Database of Randomised Controlled Trials in Hyperbaric
      Medicine(DORCTIHM) (searched April 2014) and the reference lists of articles.We
      handsearched relevant publications and contacted researchers to identify
      additional published and unpublished studies.Selection criteria Randomised
      controlled trials (RCTs) that compared the effects of adjunctive HBOT versus
      those of no HBOT (no treatment or sham).Data collection and analysis Three review
      authors independently extracted data, assessed each trial for internal validity
      and resolved differences by discussion.Main results We included 11 RCTs involving
      705 participants. The methodological quality of the trials varied. We could pool
      data only for case fatalities. No significant differences were noted in the case
      fatality rate at six months in those receiving HBOT compared with the control
      group (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.34 to 2.75, P value
      0.96). Four of 14 scale measures of disability and functional performance
      indicated improvement following HBOT, for example, the mean Trouillas Disability
      Scale score was lower with HBOT (mean difference (MD) 2.2 point reduction with
      HBOT, 95% CI 0.15 to 4.3, P value 0.04), and the mean Orgogozo Scale score was
      higher (MD 27.9 points, 95% CI 4.0 to 51.8, P value 0.02).Authors' conclusions We
      found no good evidence to show that HBOT improves clinical outcomes when applied
      during acute presentation of ischaemic stroke. Although evidence from the 11 RCTs
      is insufficient to provide clear guidelines for practice, the possibility of
      clinical benefit has not been excluded. Further research is required to better
      define the role of HBOT in this condition.

PMID- 25387993
TI  - Remission of recurrent gastrointestinal bleeding after septal reduction therapy
      in patients with hypertrophic obstructive cardiomyopathy-associated acquired von
      Willebrand syndrome.
AB  - BACKGROUND: Gastrointestinal hemorrhage is considered to be a severe complication
      of von Willebrand disease. The optimal therapy for acquired von Willebrand
      syndrome and severe gastrointestinal bleeding with hypertrophic cardiomyopathy is
      undefined. PATIENTS/METHODS: Seventy-seven patients (median age, 67 years;
      interquartile range [IQR], 56-75 years; 49% women) with hypertrophic
      cardiomyopathy underwent von Willebrand factor multimer testing and acquisition
      of bleeding history. Bleeding was detected in 27 (36%) (median age, 74 years; IQR
      66-76 years; 74% women), 20 with gastrointestinal bleeding, including 11 women
      with transfusion dependence. In these 11 women, the median duration of
      transfusion dependency was 36 months (IQR 18-44 months), and the median number of
      transfusions required was 25 (IQR 20-38). Two patients had undergone bowel
      resection for bleeding, one of them twice. Seven patients showed angiodysplasia,
      and the remainder had no endoscopic lesion. Bleeding recurred after bowel surgery
      or endoscopic intervention and medical therapy for hypertrophic cardiomyopathy in
      10 of 11 patients. Two patients had septal myectomy, and six patients underwent
      alcohol septal ablation. With the exception of one patient in whom a significant
      gradient persisted after septal ablation, after the periprocedural period,
      patients after septal reduction therapy remained free of recurrent bleeding and
      need for transfusions. CONCLUSION: Acquired von Willebrand syndrome is common in
      hypertrophic cardiomyopathy. Gastrointestinal bleeding often recurs after
      endoscopic therapy, but may be relieved by structural cardiac repair.

PMID- 25387994
TI  - Spore immobilization and its analytical performance for monitoring of aflatoxin
      M1 in milk.
AB  - Immobilization of Bacillus megaterium spores on Eppendorf tubes through physical
      adsorption has been used in the detection of aflatoxin M1 (AFM1) in milk within
      real time of 45 +/- 5 min using visual observation of changes in a chromogenic
      substrate. The appearance of a sky-blue colour indicates the absence of AFM1 in
      milk, whereas no colour change indicates the presence of AFM1 in milk at a 0.5
      ppb Codex maximum residue limit. The working performance of the immobilized
      spores was shown to persist for up to 6 months. Further, spores immobilized on 96
      well black microtitre plates by physical adsorption and by entrapment on sensor
      disk showed a reduction in detection sensitivity to 0.25 ppb within a time period
      of 20 +/- 5 min by measuring fluorescence using a microbiological plate reader
      through the addition of milk and fluorogenic substrate. A high fluorescence ratio
      indicated more substrate hydrolysis due to spore-germination-mediated release of
      marker enzymes of spores in the absence of AFM1 in milk; however, low
      fluorescence ratios indicated the presence of AFM1 at 0.25 ppb. Immobilized
      spores on 96-well microtitre plates and sensor disks have shown better
      reproducibility after storage at 4  degrees C for 6 months. Chromogenic assay
      showed 1.38% false-negative and 2.77% false-positive results while fluorogenic
      assay showed 4.16% false-positive and 2.77% false-negative results when analysed
      for AFM1 using 72 milk samples containing raw, pasteurized, and dried milk.
      Immobilization of spores makes these chromogenic and fluorogenic assays portable,
      selective, cost-effective for real-time detection of AFM1 in milk at the dairy
      farm, reception dock, and manufacturing units of the dairy industry.

PMID- 25387995
TI  - Impact of data base structure in a successful in vitro-in vivo correlation for
      pharmaceutical products.
AB  - The in vitro-in vivo correlation (IVIVC) (Food and Drug Administration 1997) aims
      to predict performances in vivo of a pharmaceutical formulation based on its in
      vitro characteristics. It is a complex process that (i) incorporates in a gradual
      and incremental way a large amount of information and (ii) requires information
      from different properties (formulation, analytical, clinical) and associated
      dedicated treatments (statistics, modeling, simulation). These results in many
      studies that are initiated and integrated into the specifications (quality target
      product profile, QTPP). This latter defines the appropriate experimental designs
      (quality by design, QbD) (Food and Drug Administration 2011, 2012) whose main
      objectives are determination (i) of key factors of development and manufacturing
      (critical process parameters, CPPs) and (ii) of critical points of
      physicochemical nature relating to active ingredients (API) and critical quality
      attribute (CQA) which may have implications in terms of efficiency, safety, and
      inoffensiveness for the patient, due to their non-inclusion. These processes
      generate a very large amount of data that is necessary to structure. In this
      context, the storage of information in a database (DB) and the management of this
      database (database management system, DBMS) become an important issue for the
      management of projects and IVIVC and more generally for development of new
      pharmaceutical forms. This article describes the implementation of a prototype
      object-oriented database (OODB) considered as a tool, which is helpful for
      decision taking, responding in a structured and consistent way to the issues of
      project management of IVIVC (including bioequivalence and bioavailability) (Food
      and Drug Administration 2003) necessary for the implementation of QTPP. 

PMID- 25387996
TI  - Cationic liposomes loaded with a synthetic long peptide and poly(I:C): a defined
      adjuvanted vaccine for induction of antigen-specific T cell cytotoxicity.
AB  - For effective cancer immunotherapy by vaccination, co-delivery of tumour antigens
      and adjuvants to dendritic cells and subsequent activation of antigen-specific
      cytotoxic T cells (CTLs) is crucial. In this study, a synthetic long peptide
      (SLP) harbouring the model CTL epitope SIINFEKL was encapsulated with the TLR3
      ligand poly(inosinic-polycytidylic acid) (poly(I:C)) in cationic liposomes
      consisting of DOTAP and DOPC. The obtained particles were down-sized to about 140
      nm (measured by dynamic light scattering) and had a positive zeta-potential of
      about 26 mV (according to laser Doppler electrophoresis). SLP loading efficiency
      was about 40% as determined by HPLC. Poly(I:C) loading efficiency was about 50%,
      as assessed from the fluorescence intensity of fluorescently labelled poly(I:C).
      Immunogenicity of the liposomal SLP vaccine was evaluated in vitro by its
      capacity to activate dendritic cells (DCs) and present the processed SLP to
      SIINFEKL-specific T cells. The effectiveness of the vaccine to activate CD8(+) T
      cells was analysed in vivo after intradermal and subcutaneous immunisation in
      mice, by measuring antigen-specific T cells in blood and spleens and assessing
      their functionality by cytokine production and in vivo cytotoxicity. The
      liposomal formulation efficiently delivered the SLP to DCs in vitro and induced a
      functional CD8(+) T cell immune response in vivo to the CTL epitope present in
      the SLP. The SLP-specific CD8(+) T cell frequency induced by the poly(I:C)
      adjuvanted liposomal SLP formulation showed an at least 25 fold increase over the
      T cell frequency induced by the poly(I:C)-adjuvanted soluble SLP. In conclusion,
      cationic liposomes loaded with SLP and poly(I:C) have potential as a powerful
      therapeutic cancer vaccine formulation. 

PMID- 25387997
TI  - Band gap grading and photovoltaic performance of solution-processed Cu(In,Ga)S2
      thin-film solar cells.
AB  - The photophysical properties of CuInxGa1-xS2 (CIGS) thin films, prepared by
      solution-based coating methods, are investigated to understand the correlation
      between the optical properties of these films and the electrical characteristics
      of solar cells fabricated using these films. Photophysical properties, such as
      the depth-dependent band gap and carrier lifetime, turn out to be at play in
      determining the energy conversion efficiency of solar cells. A double grading of
      the band gap in CIGS films enhances solar cell efficiency, even when defect
      states disturb carrier collection by non-radiative decay. The combinational
      stacking of different density films leads to improved solar cell performance as
      well as efficient fabrication because a graded band gap and reduced shunt current
      increase carrier collection efficiency. The photodynamics of minority-carriers
      suggests that the suppression of defect states is a primary area of improvement
      in CIGS thin films prepared by solution-based methods. 

PMID- 25387999
TI  - GIP1 protein is a novel cofactor that regulates DNA-binding affinity of redox
      regulated members of bZIP transcription factors involved in the early stages of
      Arabidopsis development.
AB  - In response to environmental light signals, gene expression adjustments play an
      important role in regulation of photomorphogenesis. LHCB2.4 is among the genes
      responsive to light signals, and its expression is regulated by redox-regulated
      members of G-group bZIP transcription factors. The biochemical interrelations of
      GBF1-interacting protein 1 (GIP1) and the G-group bZIP transcription factors have
      been investigated. GIP1, previously shown to enhance DNA-binding activities of
      maize GBF1 and Arabidopsis GBF3, is a plant specific protein that reduces DNA
      binding activity of AtbZIP16, AtbZIP68, and AtGBF1 under non-reducing conditions
      through direct physical interaction shown by the yeast two-hybrid and pull-down
      assays. Fluorescence microscopy studies using cyan fluorescent protein (CFP)
      fusion protein indicate that GIP1 is exclusively localized in the nucleus. Under
      non- reducing conditions, GIP1 exhibits predominantly high molecular weight
      forms, whereas it predominates in low molecular weight monomers under reducing
      conditions. While reduced GIP1 induced formation of DNA-protein complexes of G
      group bZIPs, oxidized GIP1 decreased the amount of those complexes and instead
      induced its chaperone function suggesting functional switching from redox to
      chaperone activity. Finally analysis of transgenic plants overexpressing GIP1
      revealed that GIP1 is a negative co-regulator in red and blue light mediated
      hypocotyl elongation. By regulating the repression effect by bZIP16 and the
      activation effect by bZIP68 and GBF1 on LHCB2.4 expression, GIP1 functions to
      promote hypocotyl elongation during the early stages of Arabidopsis seedling
      development.

PMID- 25388001
TI  - Navigated transcranial magnetic stimulation in amyotrophic lateral sclerosis.

PMID- 25388000
TI  - Some aspects of salinity responses in peppermint (Mentha * piperita L.) to NaCl
      treatment.
AB  - Salinity is a major stress that adversely affects plant growth and crop
      production. Understanding the cellular responses and molecular mechanisms by
      which plants perceive and adopt salinity stress is of fundamental importance. In
      this work, some of the cellular signaling events including cell death, reactive
      oxygen species (ROS) generation, and the behaviors of organelles were analyzed in
      a salt-tolerant species (Keyuan-1) of peppermint (Mentha * piperita L.) under
      NaCl treatment. Our results showed that 200 mM NaCl treatment elicited a distinct
      progress of cell death with chromatin condensation and caspase-3-like activation
      and a dramatic burst of ROS which was required for the execution of cell death.
      The major ROS accumulation occurred in the mitochondria and chloroplasts, which
      were the sources of ROS production under NaCl stress. Moreover, mitochondrial
      activity and photosynthetic capacity also exhibited the obvious decrease in the
      ROS-dependent manner under 200 mM NaCl stress. Furthermore, the activities of
      superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase
      (GR), and dehydroascorbate reductase (DHAR) as well as the contents of ascorbate
      and glutathione changed in the concentration-dependent manner under NaCl stress.
      Altogether, our data showed the execution of programmed cell death (PCD), the ROS
      dynamics, and the behaviors of organelles especially mitochondria and
      chloroplasts in the cellular responses of peppermint to NaCl stress which can be
      used for the tolerance screening, and contributed to the understanding of the
      cellular responses and molecular mechanisms of peppermint to salinity stress,
      providing the theoretic basis for the further development and utilization of
      peppermint in saline areas.

PMID- 25387998
TI  - Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit
      endothelial dysfunction--a novel mechanism for maintaining vascular function.
AB  - Endothelial dysfunction is a pathological status of the vascular system, which
      can be broadly defined as an imbalance between endothelium-dependent
      vasoconstriction and vasodilation. Endothelial dysfunction is a key event in the
      progression of many pathological processes including atherosclerosis, type II
      diabetes and hypertension. Previous reports have demonstrated that pro
      inflammatory/immunoeffector cytokines significantly promote endothelial
      dysfunction while numerous novel anti-inflammatory/immunosuppressive cytokines
      have recently been identified such as interleukin (IL)-35. However, the effects
      of anti-inflammatory cytokines on endothelial dysfunction have received much less
      attention. In this analytical review, we focus on the recent progress attained in
      characterizing the direct and indirect effects of anti
      inflammatory/immunosuppressive cytokines in the inhibition of endothelial
      dysfunction. Our analyses are not only limited to the importance of endothelial
      dysfunction in cardiovascular disease progression, but also expand into the
      molecular mechanisms and pathways underlying the inhibition of endothelial
      dysfunction by anti-inflammatory/immunosuppressive cytokines. Our review suggests
      that anti-inflammatory/immunosuppressive cytokines serve as novel therapeutic
      targets for inhibiting endothelial dysfunction, vascular inflammation and cardio-
      and cerebro-vascular diseases. 

PMID- 25388002
TI  - Macro TSH in patients with subclinical hypothyroidism.
AB  - OBJECTIVE: TSH is a sensitive indicator of thyroid function. In subclinical
      hypothyroidism, however, serum TSH concentrations are elevated despite normal
      thyroid hormone levels, and macro TSH is one of the causes. This study aimed to
      clarify the prevalence and nature of macro TSH in patients with subclinical
      hypothyroidism. DESIGN: We conducted a 2-year cross-sectional observational
      study. PATIENTS: We included 681 patients with subclinical hypothyroidism and 38
      patients with overt hypothyroidism (controls). MEASUREMENTS: Macro TSH was
      screened by polyethylene glycol (PEG) method and analysed by gel filtration
      chromatography and bioassays. RESULTS: Among 681 serum samples, 117 exhibited PEG
      precipitable TSH ratios greater than 75% (mean + 1.5 SD in controls) and were
      subjected to gel filtration chromatography. TSH was eluted at a position greater
      than 100 kDa in 11 patients with subclinical hypothyroidism (1.62%); these
      patients were diagnosed with macro TSH. The nature of macro TSH included eight
      anti-TSH autoantibodies of IgG class, two non-IgG-associated and one human anti
      mouse antibody (HAMA). Macro TSH showed low bioactivity. CONCLUSIONS: Macro TSH
      was heterogeneous, but it is mostly comprised of TSH and anti-TSH autoantibodies.
      When PEG-precipitable TSH exceeds 90% in serum samples with TSH above 10 mU/l,
      clinicians should strongly suspect the presence of macro TSH and confirm it by
      gel chromatography. Because macro TSH exhibited low bioactivity, thyroid hormone
      replacement therapy may not be required in patients with subclinical
      hypothyroidism due to macro TSH except for those with high serum free TSH levels.

PMID- 25388003
TI  - Reviewing HIV-Related Research in Emerging Economies: The Role of Government
      Reviewing Agencies.
AB  - Little research has explored the possible effects of government institutions in
      emerging economies on ethical reviews of multinational research. We conducted
      semi-structured, in-depth telephone interviews with 15 researchers, Research
      Ethics Committees (RECs) personnel, and a government agency member involved in
      multinational HIV Prevention Trials Network (HPTN) research in emerging
      economies. Ministries of Health (MOH) or other government agencies often play
      pivotal roles as facilitators or barriers in the research ethics approval
      process. Government agency RECs reviewing protocols may face particular
      challenges, as they can lack resources, be poorly organized, have inconsistent
      review processes and limited expertise, and use differing definitions of national
      interests, including upholding national reputation and avoiding potential
      exploitation and stigma of the country's population. The MOH/governmental review
      body may be affected by power dynamics and politics in study reviews; may
      consider issues both related and unrelated to research ethics as understood
      elsewhere; and may prioritize particular diseases, treatments, or interventions
      over other topics/types of research. Poor communication and deeply-rooted
      tensions may exist between sponsor and host countries, impeding optimal
      interactions and reviews. Investigators must understand and plan for the
      potential effects of governmental agencies on multinational collaborative
      research, including preserving adequate time for agency review, and contacting
      these agencies beforehand to address issues that may arise. Better understanding
      of these issues can aid and advance appropriate global scientific collaboration. 

PMID- 25388004
TI  - Expression analysis in intestinal mucosa reveals complex relations among genes
      under the association peaks in celiac disease.
AB  - Celiac disease is a chronic immune-mediated disorder with an important genetic
      component. To date, there are 57 independent association signals from 39 non-HLA
      loci, and a total of 66 candidate genes have been proposed. We aimed to
      scrutinize the functional implication of 45 of those genes by analyzing their
      expression in the disease tissue of celiac patients (at diagnosis/treatment)
      compared with non-celiac controls. Moreover, we investigated the SNP genotype
      effect in gene expression and performed coexpression analyses. Several genes
      showed differential expression among disease groups, most of them related to
      immune response. Multiple trans-eQTLs but only four cis-eQTLs were found, and
      surprisingly the genotype effect seems to be stimulus dependent as it differs
      among groups. Coexpression levels vary from higher to lower levels in active
      patients at diagnosis, treated patients and non-celiac controls respectively. A
      subset of 18 genes tightly correlated in both groups of patients but not in
      controls was identified. Interestingly, this subset of genes was influenced by
      the genotype of three SNPs. One of the SNPs, rs1018326 on chromosome two is on
      top of a known lincRNA whose function is not yet described, and whose expression
      seems to be upregulated in active disease when comparing biopsy pairs from the
      same individuals. Our results strongly suggest that the effects of disease
      associated SNPs go far beyond the oversimplistic idea of transcriptional control
      at a nearby locus. Further investigations are needed to determine how each
      variant disrupts fine-tuning mechanisms in the genome that eventually lead to
      disease. 

PMID- 25388005
TI  - A syndrome of congenital microcephaly, intellectual disability and dysmorphism
      with a homozygous mutation in FRMD4A.
AB  - A consanguineous Bedouin Israeli kindred presented with a novel autosomal
      recessive intellectual disability syndrome of congenital microcephaly, low
      anterior hairline, bitemporal narrowing, low-set protruding ears, strabismus and
      tented thick eyebrows with sparse hair in their medial segment. Brain imaging
      demonstrated various degrees of agenesis of corpus callosum and hypoplasia of the
      vermis and cerebellum. Genome-wide linkage analysis followed by fine mapping
      defined a 7.67 Mb disease-associated locus (LOD score 4.99 at theta=0 for marker
      D10S1653). Sequencing of the 48 genes within the locus identified a single non
      synonymous homozygous duplication frameshift mutation of 13 nucleotides
      (c.2134_2146dup13) within the coding region of FRMD4A, that was common to all
      affected individuals and not found in 180 non-related Bedouin controls. Three of
      50 remotely related healthy controls of the same tribe were heterozygous for the
      mutation. FRMD4A, member of the FERM superfamily, is involved in cell structure,
      transport and signaling. It regulates cell polarity by playing an important role
      in the activation of ARF6, mediating the interaction between Par3 and the ARF6
      guanine nucleotide exchange factor. ARF6 is known to modulate cell polarity in
      neurons, and regulates dendritic branching in hippocampal neurons and neurite
      outgrowth. The FRMD4 domain that is essential for determining cell polarity
      through interaction with Par3 is truncated by the c.2134_2146dup13 mutation.
      FRMD4A polymorphisms were recently suggested to be a risk factor for Alzheimer's
      disease. We now show a homozygous frameshift mutation of the same gene in a
      severe neurologic syndrome with unique dysmorphism. 

PMID- 25388007
TI  - Clinical utility gene card for: Alport syndrome - update 2014.

PMID- 25388006
TI  - Quantification of mutant E-cadherin using bioimaging analysis of in situ
      fluorescence microscopy. A new approach to CDH1 missense variants.
AB  - Missense mutations result in full-length proteins containing an amino acid
      substitution that can be neutral or deleterious, interfering with the normal
      conformation, localization, and function of a protein. A striking example is the
      presence of CDH1 (E-cadherin gene) germline missense variants in hereditary
      diffuse gastric cancer (HDGC), which represent a clinical burden for genetic
      counseling and surveillance of mutation carriers and their families. CDH1
      missense variants can compromise not only the function of E-cadherin but also its
      expression pattern. Here, we propose a novel method to characterize E-cadherin
      signature in order to identify cases with E-cadherin deregulation and functional
      impairment. The strategy includes a bioimaging pipeline to quantify the
      expression level and characterize the distribution of the protein from in situ
      immunofluorescence images. The algorithm computes 1D (dimension intensity) radial
      and internuclear fluorescence profiles to generate expression outlines and 2D
      virtual cells representing a typical cell within the populations analyzed. Using
      this new approach, we verify that cells expressing mutant forms of E-cadherin
      display fluorescence profiles distinct from those of the wild-type cells. Mutant
      proteins showed a significantly decrease of fluorescence intensity at the
      membrane and often abnormal expression peaks in the cytoplasm, reflecting the
      underlying molecular mechanism of trafficking deregulation. Our results suggest
      employing this methodology as a complementary approach to evaluate the
      pathogenicity of E-cadherin missense variants. Moreover, it can be applied to a
      wide range of proteins and, more importantly, to diseases characterized by
      aberrant protein expression or trafficking deregulation.

PMID- 25388008
TI  - Formation of the steroidal C-25 chiral center via the asymmetric alkylation
      methodology.
AB  - A novel approach for the preparation of steroids containing a chiral center at C
      25 is reported. The key stereochemistry inducing step was asymmetric alkylation
      of pseudoephenamine amides of steroidal C-26 acids. The reaction proceeded with
      high diastereoselectivity (dr > 99 : 1). The developed methodology was
      successfully applied to the synthesis of (25R)- and (25S)-cholestenoic acids as
      well as (25R)- and (25S)-26-hydroxy brassinolides. 

PMID- 25388009
TI  - Oxidative stress and post-stroke depression: possible therapeutic role of
      polyphenols?
AB  - Post-stroke depression is a common neuropsychiatric affective disorder that may
      develop after a stroke event. In addition to abnormalities in the biogenic amine
      neurotransmitters and cytokine expression induced by stroke we will focus on the
      role of oxidative stress and hypothesize that polyphenols may be useful as
      therapeutics targets for the treatment of post-stroke depression. In this paper,
      we discuss the hypothesis that increased oxidative stress in cerebral tissues
      during ischemia is implicated in the pathogenesis of depressive-like symptoms
      following stroke. There is substantive evidence regarding the role of oxidative
      stress in the pathogenesis of both stroke and depression, which provides support
      to this hypothesis. Reactive oxygen species, generated during stroke, cause
      oxidative stress, lipid peroxidation, protein oxidation, and DNA damage in neural
      tissues. The resultant pathophysiological processes in the neural tissues could
      be considered a leading mechanism in the induction of post-stroke depression.
      Antioxidants including polyphenols therefore, may play an important role in the
      outcomes of ischemia and stroke, due to their ability to protect neurons against
      oxidative stress, to mitigate ischemic damage via inhibition of lipid
      peroxidation and ability to interact with the generation of nitric oxide from the
      vascular endothelium, and also to decrease inflammation. These data suggest that
      polyphenols may therefore be a useful new therapeutic target for the treatment of
      post-stroke depression.

PMID- 25388011
TI  - Neuronanomedicine - (Part II).

PMID- 25388010
TI  - Inhibitors of the sulfur assimilation pathway in bacterial pathogens as enhancers
      of antibiotic therapy.
AB  - The rising emergence of antibiotic resistance urges the search for new strategies
      to defeat microorganisms that lead to persistent infections of the host. Tolerant
      to antibiotics, slowly replicating bacteria often cause latent and persistent
      infections that are the most challenging for pharmacological treatment.
      Persistence inside the host requires an extensive re-programming of the pathogen
      metabolic functions, due to the extremely hostile environment they face.
      Therefore, targeting key metabolic functions could result in better antibiotic
      treatments, shortened latency periods, and increased susceptibility to
      traditional antibiotics. Bacteria, differently from mammals, assimilate inorganic
      sulfur into cysteine, the precursor of a number of key metabolites including
      reducing agents, cofactors and membrane components. Inhibition of cysteine
      biosynthesis was proven to interfere heavily with the ability of pathogens to
      fight oxidative stress, to infect the host and to establish long-term infections.
      This review has the purpose of i) briefly summarizing the key structural and
      functional properties of transporters and enzymes involved in sulfur
      assimilation, ii) presenting biological evidence that supports the exploitation
      of this pathway for the identification of potential targets and, iii)
      highlighting intense efforts and advancements in the search of promising
      candidates for the development of novel compounds that enhance antibiotics
      therapy. 

PMID- 25388012
TI  - Should the incorporation of structural alerts be restricted in drug design? An
      analysis of structure-toxicity trends with aniline-based drugs.
AB  - Certain idiosyncratic adverse drug reactions (IADRs) can be triggered by
      electrophilic protein-reactive metabolites that are formed in the process of drug
      metabolism. While methodologies (e.g., structural alert concept in drug design,
      glutathione (GSH) trapping, and protein covalent binding) for examining reactive
      metabolite (RM) formation are available, predicting the IADR potential applying
      these parameters remains a significant challenge. The present work examines
      toxicity trends associated with the aniline structural alert in the top 200
      prescribed drugs of 2011 and recently approved (2009-2013) small molecule drugs,
      in relation with 30 aniline-based drugs withdrawn from commercial use or
      associated with a black box warning for IADRs. The aniline sub-structure was
      found in several drugs from the toxic, most prescribed, and recently approved
      category. RMs resulting from the bioactivation of the aniline alert was also
      noted in the three categories chosen for comparison. A major discriminator
      between the toxic drugs and the majority of drugs in the most-prescribed list,
      however, was the daily dose--drugs most frequented associated with IADRs were the
      ones with higher daily doses (exceeding hundreds of milligrams). A greater
      tolerance for IADRs was also noted with certain drugs intended to treat rare,
      unmet medical needs (e.g., cancer). Overall, the analysis suggests that
      optimization of pharmacologic potency and pharmacokinetics that would lead to a
      lower daily dose, and therefore, a lower body burden of parent drug/metabolites,
      should be taken into consideration in drug discovery.

PMID- 25388013
TI  - Plasma metabolomic profiles of breast cancer patients after short-term limonene
      intervention.
AB  - Limonene is a lipophilic monoterpene found in high levels in citrus peel.
      Limonene demonstrates anticancer properties in preclinical models with effects on
      multiple cellular targets at varying potency. While of interest as a cancer
      chemopreventive, the biologic activity of limonene in humans is poorly
      understood. We conducted metabolite profiling in 39 paired (pre/postintervention)
      plasma samples from early-stage breast cancer patients receiving limonene
      treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling
      was conducted using ultra-performance liquid chromatography coupled to a linear
      trap quadrupole system and gas chromatography-mass spectrometry. Metabolites were
      identified by comparison of ion features in samples to a standard reference
      library. Pathway-based interpretation was conducted using the human metabolome
      database and the MetaCyc database. Of the 397 named metabolites identified, 72
      changed significantly with limonene intervention. Class-based changes included
      significant decreases in adrenal steroids (P < 0.01), and significant increases
      in bile acids (P <= 0.05) and multiple collagen breakdown products (P < 0.001).
      The pattern of changes also suggested alterations in glucose metabolism. There
      were 47 metabolites whose change with intervention was significantly correlated
      to a decrease in cyclin D1, a cell-cycle regulatory protein, in patient tumor
      tissues (P <= 0.05). Here, oral administration of limonene resulted in
      significant changes in several metabolic pathways. Furthermore, pathway-based
      changes were related to the change in tissue level cyclin D1 expression. Future
      controlled clinical trials with limonene are necessary to determine the potential
      role and mechanisms of limonene in the breast cancer prevention setting.

PMID- 25388015
TI  - Comparing alternative design options for chronic disease prevention
      interventions.
AB  - BACKGROUND: While the randomized clinical trial is considered to provide the
      highest level of evidence in clinical medicine, its superiority to other study
      designs in the context of prevention studies is debated. The purpose of this
      review was (i) to gather evidence about challenges facing both randomized
      controlled trials and observational designs for the conduct of population-based
      chronic disease prevention interventions and (ii) to consider the suitability of
      recently proposed hybrid designs for population-based prevention intervention
      studies. METHODS: Rapid review methods were employed for this study. Articles
      published within 2007-2012, were included if they: (i) discussed challenges or
      benefits related to any intervention study design, (ii) compared randomized
      controlled trials (RCT) and observational designs or (iii) introduced a new study
      design potentially applicable to population-based interventions. After initial
      screening, papers retained for inclusion were subjected to content analysis and
      synthesis. RESULTS: A total of 35 included articles were reviewed and used for
      synthesis. Both RCTs and observational studies are subject to multiple
      challenges, the main being external and internal validity for RCTs and
      observational designs, respectively. Four new hybrid designs identified.
      CONCLUSION: Although any high quality design can produce high level of evidence,
      multiple challenges with prevention intervention RCTs or observational studies
      identified. New hybrid designs that carry benefits of randomized and
      observational methods may be the road ahead for to assess the effects of
      population-based interventions.

PMID- 25388014
TI  - A multiplexable, microfluidic platform for the rapid quantitation of a biomarker
      panel for early ovarian cancer detection at the point-of-care.
AB  - Point-of-care (POC) diagnostic platforms have the potential to enable low-cost,
      large-scale screening. As no single biomarker is shed by all ovarian cancers,
      multiplexed biomarker panels promise improved sensitivity and specificity to
      address the unmet need for early detection of ovarian cancer. We have configured
      the programmable bio-nano-chip (p-BNC)-a multiplexable, microfluidic, modular
      platform-to quantify a novel multi-marker panel comprising CA125, HE4, MMP-7, and
      CA72-4. The p-BNC is a bead-based immunoanalyzer system with a credit-card-sized
      footprint that integrates automated sample metering, bubble and debris removal,
      reagent storage and waste disposal, permitting POC analysis. Multiplexed p-BNC
      immunoassays demonstrated high specificity, low cross-reactivity, low limits of
      detection suitable for early detection, and a short analysis time of 43 minutes.
      Day-to-day variability, a critical factor for longitudinally monitoring
      biomarkers, ranged between 5.4% and 10.5%, well below the biologic variation for
      all four markers. Biomarker concentrations for 31 late-stage sera correlated well
      (R(2) = 0.71 to 0.93 for various biomarkers) with values obtained on the Luminex
      platform. In a 31 patient cohort encompassing early- and late-stage ovarian
      cancers along with benign and healthy controls, the multiplexed p-BNC panel was
      able to distinguish cases from controls with 68.7% sensitivity at 80%
      specificity. Utility for longitudinal biomarker monitoring was demonstrated with
      prediagnostic plasma from 2 cases and 4 controls. Taken together, the p-BNC shows
      strong promise as a diagnostic tool for large-scale screening that takes
      advantage of faster results and lower costs while leveraging possible improvement
      in sensitivity and specificity from biomarker panels.

PMID- 25388016
TI  - Green areas around homes reduce atopic sensitization in children.
AB  - BACKGROUND: Western lifestyle is associated with high prevalence of allergy,
      asthma and other chronic inflammatory disorders. To explain this association, we
      tested the 'biodiversity hypothesis', which posits that reduced contact of
      children with environmental biodiversity, including environmental microbiota in
      natural habitats, has adverse consequences on the assembly of human commensal
      microbiota and its contribution to immune tolerance. METHODS: We analysed four
      study cohorts from Finland and Estonia (n = 1044) comprising children and
      adolescents aged 0.5-20 years. The prevalence of atopic sensitization was
      assessed by measuring serum IgE specific to inhalant allergens. We calculated the
      proportion of five land-use types--forest, agricultural land, built areas,
      wetlands and water bodies--in the landscape around the homes using the CORINE2006
      classification. RESULTS: The cover of forest and agricultural land within 2-5 km
      from the home was inversely and significantly associated with atopic
      sensitization. This relationship was observed for children 6 years of age and
      older. Land-use pattern explained 20% of the variation in the relative abundance
      of Proteobacteria on the skin of healthy individuals, supporting the hypothesis
      of a strong environmental effect on the commensal microbiota. CONCLUSIONS: The
      amount of green environment (forest and agricultural land) around homes was
      inversely associated with the risk of atopic sensitization in children. The
      results indicate that early-life exposure to green environments is especially
      important. The environmental effect may be mediated via the effect of
      environmental microbiota on the commensal microbiota influencing immunotolerance.

PMID- 25388017
TI  - The supreme intercostal artery in its most rudimentary form does not branch off
      any intercostal arteries.

PMID- 25388019
TI  - Corrigendum: Number-induced shifts in spatial attention: a replication study.
AB  - [This corrects the article on p. 987 in vol. 5, PMID: 25309472.]. 

PMID- 25388018
TI  - Use of intravenous immunoglobulin in critically ill patients.
AB  - Intravenous immunoglobulin (IVIG) has been suggested for the treatment of many
      ailments due to its ability to modulate the immune system and to provide passive
      immunity to commonly circulating pathogens. Its use as primary and adjunctive
      therapy for the treatment of conditions affecting critically ill patients is an
      attractive option, especially when alternative therapy does not exist. The body
      of literature on the use of IVIG for the treatment of several serious conditions,
      including sepsis, toxic shock syndrome, acute myocarditis, Stevens-Johnson
      syndrome, toxic epidermal necrolysis, and H1N1 influenza, were reviewed. Despite
      advances in treatment of these conditions since they were first described, there
      remains a paucity of well-designed studies on the use of IVIG for their
      treatment. Therefore, the use of IVIG for treatment of these conditions remains
      controversial. 

PMID- 25388023
TI  - Studying localized corrosion using liquid cell transmission electron microscopy.
AB  - Localized corrosion of Cu and Al thin films exposed to aqueous NaCl solutions was
      studied using liquid cell transmission electron microscopy (LCTEM). We
      demonstrate that potentiostatic control can be used to initiate pitting and that
      local compositional changes, due to focused ion beam implantation of Au(+) ions,
      can modify the corrosion susceptibility of Al films. 

PMID- 25388022
TI  - Calcium metabolism, vitamin D and bone mineral density after bariatric surgery.
AB  - SUMMARY: Lower bone mineral density, vitamin D deficiency, lower lean body mass,
      greater loss of excess weight, and increased bone turnover are complications
      found after bariatric surgery correlated in the literature with increased risk of
      fractures. The prevention and treatment of such complications should begin
      immediately after surgery. INTRODUCTION: The aims of the study were to evaluate
      bone mass in patients undergoing bariatric surgery by the Wittgrove technique
      after 1 year of the procedure and correlate it with body composition, weight
      loss, 25OH vitamin D levels, and markers of bone metabolism. METHODS: The
      operated group (OG) participated in a clinical consultation; a blood sample taken
      and a body composition; and bone mineral density assessment by dual energy X-ray
      absorptiometry (DXA). The results were compared with a control group (CG).
      RESULTS: Fifty-six subjects in the OG and 27 in the CG were included. The bone
      mineral density (BMD), after the surgery, at the lumbar spine (LS) was lower in
      the OG than in the CG. There was a positive correlation between total body (TB)
      BMD with 25OHD, body mass index (BMI), and lean mass and an inverse correlation
      with percentage of excess weight loss (%EWL). Vitamin D deficiency was seen in
      60.41% (OG) and in 16.6% (CG). PTH was higher in the OG, with secondary
      hyperparathyroidism in 41.7%. In 26.5% and 14.2% of the OG, ALP and OC levels
      were above the reference values. In <50 years, elevated values of carboxy
      terminal telopeptide (CTX) were found in 66.7% of patients. A difference was
      observed in the variation of CTX between 12 and 18 months when compared to over
      24 months. CONCLUSIONS: Lower BMD was observed, correlated with lower lean body
      mass and greater loss of excess weight. Vitamin D deficiency with high prevalence
      of secondary hyperparathyroidism and high bone turnover was detected. The
      prevention of bone loss should be initiated in the first months after surgery,
      which is a period associated with severe muscle loss and increased bone turnover.

PMID- 25388024
TI  - A case-matched comparison and meta-analysis comparing pylorus-resecting
      pancreaticoduodenectomy with pylorus-preserving pancreaticoduodenectomy for the
      incidence of postoperative delayed gastric emptying.
AB  - OBJECTIVES: This study was conducted to compare the incidences of delayed gastric
      emptying (DGE) following pylorus-resecting pancreaticoduodenectomy (PrPD) and
      pylorus-preserving pancreaticoduodenectomy (PpPD), respectively. METHODS: Data
      for 37 patients submitted to PrPD were compared with data for a matched number of
      patients submitted to PpPD during the same period. A meta-analysis of comparative
      studies of the two techniques was also carried out. The primary endpoint was the
      rate of DGE (grades A-C) defined according to the International Study Group of
      Pancreatic Surgery criteria. RESULTS: In the case-matched comparison, both
      overall DGE (six PrPD patients and 17 PpPD patients; P = 0.006) and clinically
      relevant DGE (one PrPD and eight PpPD patients; P = 0.013) occurred significantly
      less often in the PrPD group than in the PpPD group. Based on eight non
      randomized clinical trials and two randomized clinical trials involving 804
      subjects, the meta-analysis further confirmed a significant reduction in DGE with
      pooled odds ratios of 0.33 [95% confidence interval (CI) 0.17-0.63; P < 0.001]
      and 0.13 (95% CI 0.05-0.40; P < 0.001) for overall DGE and clinically relevant
      DGE, respectively. Other complications and mortality were similar in both groups.
      CONCLUSIONS: Pylorus-resecting pancreaticoduodenectomy is a safe procedure
      associated with less severe and less frequent postoperative DGE than PpPD.

PMID- 25388025
TI  - A two-component, multimeric endolysin encoded by a single gene.
AB  - Bacteriophage endolysins are bacterial cell wall degrading enzymes whose
      potential to fight bacterial infections has been intensively studied. Endolysins
      from Gram-positive systems are typically described as monomeric and as having a
      modular structure consisting of one or two N-terminal catalytic domains (CDs)
      linked to a C-terminal region responsible for cell wall binding (CWB). We show
      here that expression of the endolysin gene lys170 of the enterococcal phage
      F170/08 results in two products, the expected full length endolysin (Lys170FL)
      and a C-terminal fragment corresponding to the CWB domain (CWB170). The latter is
      produced from an in-frame, alternative translation start site. Both polypeptides
      interact to form the fully active endolysin. Biochemical data strongly support a
      model where Lys170 is made of one monomer of Lys170FL associated with up to three
      CWB170 subunits, which are responsible for efficient endolysin binding to its
      substrate. Bioinformatics analysis indicates that similar secondary translation
      start signals may be used to produce and add independent CWB170-like subunits to
      different enzymatic specificities. The particular configuration of endolysin
      Lys170 uncovers a new mode of increasing the number of CWB motifs associated to
      CD modules, as an alternative to the tandem repetition typically found in
      monomeric cell wall hydrolases. 

PMID- 25388026
TI  - Is the inherence heuristic simply WEIRD?
AB  - Although many studies suggest that children and adults focus more on internal
      causes rather than situational causes to explain observed patterns, such findings
      may be more limited to WEIRD populations (western, educated, industrialized,
      rich, democratic) samples. Evidence from cross-cultural studies may point to
      several distinct attribution mechanisms with their culturally specific deployment
      reflecting both a developmental achievement as well as a possible signal of group
      boundaries. 

PMID- 25388027
TI  - Can the inherence heuristic explain vitalistic reasoning?
AB  - Inherence is an important component of psychological essentialism. By drawing on
      vitalism as a way in which to explain this link, however, the authors appear to
      conflate causal explanations based on fixed features with those based on general
      causal forces. The disjuncture between these two types of explanatory principles
      highlights potential new avenues for the inherence heuristic. 

PMID- 25388028
TI  - Why we assume it's all good: the role of theory of mind in early inherent feature
      inferences.
AB  - Cimpian & Salomon's (C&S's) characterization of a domain-general inherence
      heuristic, available to young children, underplays the importance of our early
      interest in and recognition of agency, intentionality, and mental life. A
      consideration of the centrality of desires, goals, and agency in our earliest
      reasoning suggests an alternative, perhaps complementary, account of our tendency
      to be satisfied with the status quo. 

PMID- 25388029
TI  - The inherence heuristic: a key theoretical addition to understanding social
      stereotyping and prejudice.
AB  - Prior work has detailed the constructivist processes that lead individuals to
      categorize others along particular dimensions (e.g., gender) and generate the
      content (e.g., stereotypes) and affect (e.g., prejudices) associated with social
      groups. The inherence heuristic is a novel mechanism that appears to shape the
      content and rigidity of children's social stereotypes and prejudices. 

PMID- 25388030
TI  - The psychology of inherence is self-referential (and that is a good thing).
AB  - Cimpian & Salomon (C&S) appear to characterize the inherence heuristic and
      essentialism as unwise or childish aspects of human reasoning. But actually,
      these cognitive modes lie at the core of statistical analysis across all of the
      quantitative sciences, including the developmental cognitive psychology in which
      the argument here is couched. Their whole argument is as much an example of its
      topic as an analysis of it. 

PMID- 25388031
TI  - Not so fast, and not so easy: essentialism doesn't emerge from a simple
      heuristic.
AB  - Cimpian & Salomon's (C&S's) proposal comes unstuck on precisely the claim that
      inherence is an heuristic, able to deliver simple, shallow outputs that are right
      most of the time. Instead, the inherence heuristic delivers outputs that imply it
      is not an heuristic after all, and is simply too fast and too easy a mechanism to
      do the job of explaining categorisations. 

PMID- 25388032
TI  - Inherence is an aspect of psychological essentialism.
AB  - Inherence is not a distinct construct from psychological essentialism; it is one
      of several underlying beliefs. I propose that inherence is only one entry point
      to the perception of an essence and posit that context may influence which
      aspects of essentialist reasoning precede inferring an essence. I also discuss
      how psychological essentialism can uniquely account for violations of category
      based expectancies. 

PMID- 25388033
TI  - A single cognitive heuristic process meets the complexity of domain-specific
      moral heuristics.
AB  - The inherence heuristic (a) offers modest insights into the complex nature of
      both the is-ought tension in moral reasoning and moral reasoning per se, and (b)
      does not reflect the complexity of domain-specific moral heuristics. Formal and
      general in nature, we contextualize the process described as "inherence
      heuristic" in a web of domain-specific heuristics (e.g., agent specific; action
      specific; consequences specific). 

PMID- 25388034
TI  - Do we need the inherence heuristic to explain the bias towards inherent
      explanations?
AB  - It is clear that people often make unwarranted inherence-based explanations, but
      it is less clear that explaining this fact requires the inherence heuristic.
      Instead, it can be explained by a more general explanatory apparatus operating on
      the most readily available information, which, depending on the nature of that
      information, outputs both inherent and noninherent explanations. 

PMID- 25388035
TI  - Why does the "mental shotgun" fire system-justifying bullets?
AB  - We suggest that people privilege explanations relying on inherent rather than
      contingent factors not only because of an innate cognitive tendency to monitor
      reality, but because doing so satisfies the desire to perceive the societal
      status quo as legitimate. In support, we describe experimental studies linking
      the activation of system justification motivation to the endorsement of inherence
      based (essentialist) explanations. 

PMID- 25388036
TI  - The inherence heuristic: a basis for psychological essentialism?
AB  - Cimpian & Salomon (C&S) provide evidence that psychological essentialism rests on
      a domain-general attention to inherent causes. We suggest that the inherence
      heuristic may itself be undergirded by a more foundational cognitive bias,
      namely, a realist assumption about environmental regularities. In contrast, when
      considering specific representations, people may be more likely to activate
      attention to non-inherent, contingent, and historical links. 

PMID- 25388037
TI  - The inherence heuristic is inherent in humans.
AB  - The inherence heuristic is too broad as a theoretical notion. The authors are at
      risk of applying their own heuristic in supporting itself. Nonetheless the
      article provides useful insight into the ways in which people overestimate the
      coherence and completeness of their understanding of the world. 

PMID- 25388038
TI  - The essence of essentialism?
AB  - As an account of the cognitive processes that support psychological essentialism,
      the inherence heuristic clarifies the basis of individual differences in
      essentialist thinking, and how they are associated with prejudice. It also
      illuminates the contextual variability of social essentialism, and where its
      conceptual boundaries should be drawn. 

PMID- 25388039
TI  - Quiddity and haecceity as distinct forms of essentialism.
AB  - Psychological essentialism operates in two realms that have consequences for our
      attitudes towards groups and individuals. Although essentialism is more familiar
      in the context of biological group membership, it can also be evoked when
      considering unique artefacts, especially when they are emotionally significant
      items. 

PMID- 25388040
TI  - The inherent bias in positing an inherence heuristic.
AB  - There are two problems with Cimpian & Salomon's (C&S's) claim that an innate
      inherence heuristic is part of our cognitive makeup. First, some of their
      examples of inherent features do not seem to accord with the authors' own
      definition of inherence. Second, rather than posit an inherence heuristic to
      explain why humans rely more heavily on inherent features, it may be more
      parsimonious to do so on the basis of aspects of the world itself and our
      relationship to it. 

PMID- 25388041
TI  - Does the inherence heuristic take us to psychological essentialism?
AB  - We argue that the claim that essence-based causal explanations emerge, hydra
      like, from an inherence heuristic is incomplete. No plausible mechanism for the
      transition from concrete properties, or cues, to essences is provided. Moreover,
      the fundamental shotgun and storytelling mechanisms of the inherence heuristic
      are not clearly enough specified to distinguish them, developmentally, from
      associative or causal networks. 

PMID- 25388042
TI  - Is it about "pink" or about "girls"? The inherence heuristic across social and
      nonsocial domains.
AB  - The inherence heuristic provides an intriguing and novel explanation for early
      thought in a variety of domains. Exploring similarities and differences in
      inherent reasoning across social and nonsocial domains can help us understand the
      role that inherent thinking plays in the development of human reasoning and the
      process by which more elaborate essentialist reasoning develops. 

PMID- 25388043
TI  - Systematic revisions to inherent notions may shape improvements in cognitive
      infrastructure.
AB  - The proposed inherence heuristic centers on perceivers' failure to systematically
      consider external, historical factors when explaining observed patterns. We
      stress that this does not preclude the potential of subsequently encountered
      information to challenge intuitions. Drawing on models of diversity-defined
      social cognition, we discuss how an updating mechanism may reciprocally shape the
      cognitive infrastructure that underlies reliance on heuristic systems. 

PMID- 25388044
TI  - Is the inherence heuristic needed to understand system-justifying tendencies
      among children?
AB  - Evidence that children's system-justifying preferences track the extent of group
      based status differences is consistent with the inherence heuristic account.
      However, evidence that children are inferring inherence per se, or that such
      inferences are the cause of system-justifying preferences, is missing. We note
      that, until direct evidence of the inherence heuristic is available, alternative
      models should not be ignored. 

PMID- 25388045
TI  - Owning up to the role of historical information.
AB  - Although the inherence heuristic is a versatile cognitive process that addresses
      a wide range of psychological phenomena, we propose that ownership information
      represents an important test case for evaluating both the boundaries of Cimpian &
      Salomon's (C&S's) model (e.g., is the inherence heuristic meaningfully limited to
      only inherent factors?) and its effectiveness as a mechanism for explaining
      psychological essentialism. 

PMID- 25388046
TI  - The social aetiology of essentialist beliefs.
AB  - This commentary highlights the importance of attending to the sociocultural
      contexts that foster essentialist ideas. It contends that Cimpian & Salomon's
      (C&S's) model undervalues the extent to which the development of essentialist
      beliefs is contingent on social experience. The result is a restriction of the
      model's applicability to real-world instances of essentialism-fuelled prejudice
      and discrimination. 

PMID- 25388047
TI  - Is psychological essentialism an inherent feature of human cognition?
AB  - Recent evidence shows that psychological essentialism is neither a universal nor
      stable feature of human cognition. The extent to which people report essentialist
      intuitions varies enormously across cultures and education levels, and is also
      influenced by subtle, normatively irrelevant contextual manipulations. These
      results challenge the notion that the human mind is "fitted" with a built-in
      inherence heuristic that produces essentialist intuitions. 

PMID- 25388048
TI  - The representation of inherent properties.
AB  - Research on the representation of generic knowledge suggests that inherent
      properties can have either a principled or a causal connection to a kind. The
      type of connection determines whether the outcome of the storytelling process
      will include intuitions of inevitability and a normative dimension and whether it
      will ground causal explanations. 

PMID- 25388049
TI  - The developmental and evolutionary origins of psychological essentialism lie in
      sortal object individuation.
AB  - Cimpian & Salomon (C&S) present promising steps towards understanding the
      cognitive underpinnings of adult essentialism. However, their approach is less
      convincing regarding ontogenetic and evolutionary aspects. In contrast to C&S's
      claim, the so-called inherence heuristic, though perhaps vital in adult
      reasoning, seems an implausible candidate for the developmental and evolutionary
      foundations of psychological essentialism. A more plausible candidate is kind
      based object individuation that already embodies essentialist modes of thinking
      and that is present in infants and nonhuman primates. 

PMID- 25388050
TI  - Inherence-based views of social categories.
AB  - Children adopt an inherence-based view of some social categories, viewing certain
      social categories as reflecting the inherent features of their members. Thinking
      of social categories in these terms contributes to prejudice and intergroup
      conflict. Thus, understanding what leads children to apply inherence-based views
      to particular categories could provide new direction for efforts to reduce these
      negative social phenomena. 

PMID- 25388051
TI  - The causes of characteristic properties: insides versus categories.
AB  - Cimpian & Salomon (C&S) propose that the inherence heuristic, a tendency to
      explain the behavior and other properties of things in terms of their intrinsic
      characteristics, precedes and explains "essentialist thinking" about natural
      kinds. This commentary reviews evidence that it is rather essentialism (or
      something like it) that precedes the assumption of inherence, and suggests that
      essentialism can do without the inherence heuristic altogether. 

PMID- 25388052
TI  - System-justifying motives can lead to both the acceptance and the rejection of
      innate explanations for group differences.
AB  - Recent experimental evidence indicates that intuitions about inherence and system
      justification are distinct psychological processes, and that the inherence
      heuristic supplies important explanatory frameworks that are accepted or rejected
      based on their consistency with one's motivation to justify the system. 

PMID- 25388053
TI  - Generalizing a model beyond the inherence heuristic and applying it to beliefs
      about objective value.
AB  - The inherence heuristic is characterized as part of an instantiation of a more
      general model that describes the interaction between undeveloped intuitions,
      produced by System 1 heuristics, and developed beliefs, constructed by System 2
      reasoning. The general model is described and illustrated by examining another
      instantiation of the process that constructs belief in objective moral value. 

PMID- 25388054
TI  - Inherence heuristic versus essentialism: Issues of antecedence and cognitive
      mechanism.
AB  - We argue (1) that the empirical evidence offered by the authors is insufficient
      to sustain their claim; (2) that, beyond methodological problems, the proposed
      underlying cognitive mechanism is largely speculative and that a reverse, more
      motivational, path is equally plausible; and (3) that the distinction and
      antecedence of inherence intuitions with respect to essentialist beliefs remain
      to be demonstrated. 

PMID- 25388056
TI  - An unusual case showing fatal rupture of a gastric ulcer or gastromalacia? The
      importance/role of histology for differential diagnosis.
AB  - Gastromalacia is the acute autolytic erosion of the gastric wall. It generally
      occurs postmortem, and it appears as a slimy brownish black region of the wall
      which occurs principally in the gastric fundus. A 59-year-old woman died in the
      Emergency Department following a 2-day period of mild abdominal pain, vomiting,
      and diarrhea. A forensic autopsy was performed which revealed a rupture of the
      gastric fundus that had caused leakage of gastric content into the abdominal
      cavity. There was no macroscopic evidence of peritonitis, and the stomach wall
      adjacent to the rupture site showed marked thinning. The gross appearance was
      typical of gastromalacia. In contrast, histological observations revealed the
      presence of an ulcer at the site of perforation and a severe acute inflammatory
      reaction indicating a robust reaction with an antemortem rupture. 

PMID- 25388055
TI  - Increase of circulating stromal cell-derived factor-1 in heart failure patients.
AB  - BACKGROUND: The role of circulating stromal cell-derived factor-1 (SDF-1) in
      heart failure (HF) has not been defined. The aim of this study was to examine the
      circulating SDF-1 levels in hospitalized heart failure (HHF) patients. METHODS:
      Circulating SDF-1 and other clinical variables, including N-terminal pro-brain
      natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and echocardiographic
      parameters, were measured in HHF patients (n = 69) and healthy control subjects
      (n = 35). RESULTS: The circulating SDF-1 level was significantly greater in
      patients with HF (5,101 +/- 1,977 pg/ml) compared with the control subjects
      (1,879 +/- 1,417 pg/ml; p < 0.001). Circulating SDF-1 levels were positively
      correlated with NT-proBNP (r = 0.46 p < 0.001) and CRP (r = 0.53 p < 0.001)
      levels, and negatively correlated with left ventricular ejection fraction values
      (r = - 0.41, p < 0.001). CONCLUSION: The level of circulating SDF-1 increases in
      HHF patients.

PMID- 25388057
TI  - Assessing localized skin-to-fat water in arms of women with breast cancer via
      tissue dielectric constant measurements in pre- and post-surgery patients.
AB  - BACKGROUND: Skin-to-fat tissue dielectric constant (TDC) values at 300 MHz
      largely depend on tissue water and provide a rapid way to assess skin water by
      touching skin with a probe for approximately 10 s. This method has been used to
      investigate lymphedema features accompanying breast cancer (BC), but
      relationships between TDC and nodes removed or symptoms is unclear. Our goals
      were: (1) to compare TDC values in BC patients prior to surgery (group A) and in
      patients who had BC-related surgery (group B) to determine if TDC of group B were
      related to nodes removed and reported symptoms and (2) to develop tentative
      lymphedema-detection thresholds. METHODS: Arm volumes and TDC values of at-risk
      and contralateral forearms and biceps were determined in 103 women awaiting
      surgery for BC and 104 women who had BC-related surgery 26.3 +/- 17.5 months
      prior to evaluation. Inter-arm ratios (at-risk/contralateral) were determined and
      patients answered questions about lymphedema-related symptoms. RESULTS: Inter-arm
      TDC ratios for group A forearm and biceps were respectively 1.003 +/- 0.096 and
      1.012 +/- 0.143. Group B forearm ratios were significantly greater, and among
      group B patients who reported at least one symptom there was a significant
      correlation between TDC ratios and symptom burden and nodes removed. CONCLUSIONS:
      Inter-arm TDC ratios are significantly related to symptoms and nodes removed.
      Ratios increase with increasing symptom score and might be used to detect pre
      clinical unilateral lymphedema using TDC ratio thresholds of 1.30 for forearm and
      1.45 for biceps. Threshold confirmation awaits targeted prospective studies but
      can serve as guideposts to provide quantitative and easily done tracking
      assessments during follow-up visits.

PMID- 25388058
TI  - A risk model to determine surgical treatment in patients with thyroid nodules
      with indeterminate cytology.
AB  - BACKGROUND: Thyroid nodules are present in 19-67 % of the population and have a 5
      10 % risk of malignancy. Fine needle aspiration biopsies are indeterminate in 20
      30 % of patients, often necessitating thyroid surgery for diagnosis. We
      hypothesized that developing a risk model incorporating factors associated with
      malignancy could help predict the risk of malignancy in patients with
      indeterminate thyroid nodules. METHODS: We identified 151 patients with a
      cytologic diagnosis of follicular neoplasm (Bethesda IV) who progressed to
      surgery. We retrospectively analyzed demographic, clinical, sonographic, and
      cytological variables in relation to thyroid carcinoma. RESULTS: Of 151 patients,
      51 (33.8 %) had a final diagnosis of thyroid carcinoma. Papillary carcinoma was
      diagnosed in 34 patients (66.7 %), follicular carcinoma in 15 (29.4 %), and
      Hurthle cell carcinoma in 2 (3.9 %). On univariate analysis, younger age, male
      gender, tobacco use, larger nodule size, and calcifications on ultrasound,
      nuclear atypia on cytology, and suspicious frozen section were associated with
      the presence of malignancy. When determining odds ratios, four factors were most
      predictive of malignancy: nodule calcification [odds ratio (OR) 6.37, 95 %
      confidence interval (CI) 1.62-25.1, p < 0.01] and nodule size (OR 1.75, 95 % CI
      1.19-2.57, p < 0.01) on ultrasound, nuclear atypia on cytology (OR 4.91, 95 % CI
      1.90-12.66, p < 0.01), and tobacco use (OR 4.59, 95 % CI 1.30-16.27, p < 0.02). A
      multivariable model based on these four factors resulted in a c-statistic of
      0.82. CONCLUSIONS: A multivariable model based on calcification, nodule size,
      nuclear atypia, and tobacco use may predict the risk of thyroid cancer requiring
      a total thyroidectomy in patients with thyroid nodules of indeterminate cytology.

PMID- 25388059
TI  - Sentinel Lymph Node Biopsy in Thick-Melanoma Patients (N=350): What is Its
      Prognostic Role?
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is currently recommended for
      patients with intermediate-thickness melanomas (T2-T3). Historically, T4 melanoma
      patients have not been considered good candidates for SLNB because of the high
      risk of distant progression. However, some authors suggest that T4 melanoma
      patients could be considered as a heterogeneous group that could benefit from
      SLNB. METHODS: We retrospectively analyzed 350 patients with thick (>4 mm)
      melanomas between 1999 and 2011. Patients were stratified into three groups
      depending on the results of SLNB: (1) 94 SLNB-negative; (2) 84 SLNB-positive; and
      (3) 172 SLNB not performed (observation group). The associations of clinical
      pathologic features with the result of SLNB, disease-free interval (DFI), and
      disease-specific survival (DSS) were analyzed. RESULTS: Multivariate analyses
      confirmed a better prognosis for SLN-negative patients compared with patients in
      the observation group (DSS hazard ratio [HR] 0.62, p = 0.03; DFI HR 0.47, p <
      0.001). The observation group was shown to have the same prognosis as the
      positive-sentinel lymph node group, when adjusted for principal confounders in
      the model. CONCLUSIONS: We confirmed that thick-melanoma patients are a
      heterogeneous group with different prognosis. In our experience, SLNB allowed for
      an appropriate stratification of patients in different survival groups. On the
      basis of our results, we strongly recommend the routine execution of SLNB in
      cases of primary melanoma thicker than 4 mm.

PMID- 25388060
TI  - Escalation of socioeconomic disparities among patients with colorectal cancer
      receiving advanced surgical treatment.
AB  - BACKGROUND: As tumor burden increases in colorectal cancer, treatment complexity
      progresses from colectomy to hepatectomy and lastly to cytoreductive surgery with
      heated intraperitoneal chemotherapy (CRS-HIPEC). The aim of this study was to
      evaluate whether disparities exist in the access to progressively more complex
      surgical treatment options. METHODS: Patients undergoing surgery for colorectal
      cancer were grouped by treatment type: group 1 (n = 224) underwent colectomy for
      nonmetastatic disease, group 2 (n = 112) underwent hepatectomy for liver
      metastasis, and group 3 (n = 112) underwent CRS-HIPEC for carcinomatosis.
      RESULTS: Whites were predominant in the HIPEC group (71.4 %) compared to the
      hepatectomy (67.9 %) and colectomy (57.6 %) groups (p = 0.025). The majority of
      the privately insured patients were in the HIPEC group (70.5 %) compared to the
      hepatectomy (56.2 %) and colectomy (30.4 %) groups (p < 0.0001). Distance
      traveled to the hospital was farthest on average in the HIPEC group (104.6 +/-
      258.3 km) compared to the hepatectomy (29.0 +/- 28.0 km) or colectomy (26.4  +/-
      66.2 km) group (p < 0.0001). Mean household income also varied between the three
      groups, with HIPEC patients earning $56,957 (+/-24,124), hepatectomy patients
      earning $56,999 (+/-28,588), and colectomy patients earning ($51,518 +/- 24,201)
      (p = 0.0503) on average per year. The HIPEC cohort contained a higher proportion
      of English speakers (90.2 %) than the other groups (hepatectomy 87.9 %, colectomy
      85.3 %); however, this difference was not statistically significant (p = 0.43).
      CONCLUSIONS: CRS-HIPEC is not accessed equally across all socioeconomic groups.
      Patients undergoing HIPEC were most often white, English speaking, and privately
      insured; had a higher mean income; and had traveled the greatest distances on
      average to access surgical care.

PMID- 25388061
TI  - A nomogram to predict overall survival and disease-free survival after curative
      resection of gastric adenocarcinoma.
AB  - BACKGROUND: The American Cancer Society projects there will be over 22,000 new
      cases, resulting in nearly 11,000 deaths, related to gastric adenocarcinoma in
      the US in 2014. The aim of the current study was to find clinicopathologic
      variables associated with disease-free survival (DFS) and overall survival (OS)
      following curative resection of gastric adenocarcinoma, and create a nomogram for
      individual risk prediction. METHODS: A nomogram to predict DFS and OS following
      surgical resection of gastric adenocarcinoma was constructed using a multi
      institutional cohort of patients who underwent surgery for primary gastric
      adenocarcinoma at seven major institutions in the US between January 2000 and
      August 2013. Discrimination and calibration of the nomogram were tested by C
      statistic, Kaplan-Meier curves, and calibration plots. RESULTS: A total of 719
      patients who underwent surgery for primary gastric adenocarcinoma were included
      in the study. Using the backward selection of clinically relevant variables with
      Akaike information criteria, age, sex, tumor site, depth of invasion, and lymph
      node ratio (LNR) were selected as factors predictive of OS, while age, tumor
      site, depth of invasion, and LNR were incorporated in the prediction of DFS. A
      nomogram was constructed to predict OS and DFS using these variables.
      Discrimination and calibration of the nomogram revealed good predictive abilities
      (C-index, DFS 0.711; OS 0.702). CONCLUSION: Independent predictors of recurrence
      and death following surgery for primary gastric adenocarcinoma were used to
      create a nomogram to predict DFS and OS. The nomogram was able to stratify
      patients into prognostic groups, and performed well on internal validation.

PMID- 25388062
TI  - Hand leading and hand taking gestures in autism and typically developing
      children.
AB  - Children with autism use hand taking and hand leading gestures to interact with
      others. This is traditionally considered to be an example of atypical behaviour
      illustrating the lack of intersubjective understanding in autism. However the
      assumption that these gestures are atypical is based upon scarce empirical
      evidence. In this paper I present detailed observations in children with autism
      and typically developing children, suggesting that hand-leading gestures may be
      an adaptive form of interaction in typically developing children neglected by
      mainstream developmental psychology. I conclude that, although there may be
      features differentiating how these gestures are used in autism and typical
      children, systematic research on them is needed to clarify their nature and
      significance for both typical and atypical development. 

PMID- 25388063
TI  - Editorial.

PMID- 25388064
TI  - Auditory and vestibular dysfunctions in systemic sclerosis: literature review.
AB  - PURPOSE: To describe the prevalence of auditory and vestibular dysfunction in
      individuals with systemic sclerosis (SS) and the hypotheses to explain these
      changes. RESEARCH STRATEGY: We performed a systematic review without meta
      analysis from PubMed, LILACS, Web of Science, SciELO and SCOPUS databases, using
      a combination of keywords "systemic sclerosis AND balance OR vestibular" and
      "systemic sclerosis AND hearing OR auditory." SELECTION CRITERIA: We included
      articles published in Portuguese, Spanish, or English until December 2011 and
      reviews, letters, and editorials were excluded. We found 254 articles, out of
      which 10 were selected. DATA ANALYSIS: The study design was described, and the
      characteristics and frequency of the auditory and vestibular dysfunctions in
      these individuals were listed. Afterwards, we investigated the hypothesis built
      by the authors to explain the auditory and vestibular dysfunctions in SS.
      RESULTS: Hearing loss was the most common finding, with prevalence ranging from
      20 to 77%, being bilateral sensorineural the most frequent type. It is
      hypothesized that the hearing impairment in SS is due to vascular changes in the
      cochlea. The prevalence of vestibular disorders ranged from 11 to 63%, and the
      most frequent findings were changes in caloric testing, positional nystagmus,
      impaired oculocephalic response, changes in clinical tests of sensory
      interaction, and benign paroxysmal positional vertigo. CONCLUSION: High
      prevalence of auditory and vestibular dysfunctions in patients with SS was
      observed. Conducting further research can assist in early identification of these
      abnormalities, provide resources for professionals who work with these patients,
      and contribute to improving the quality of life of these individuals.

PMID- 25388065
TI  - Screening tools for dysphagia: a systematic review.
AB  - PURPOSE: To perform a systematic review of screening instruments for dysphagia
      available in the literature. METHODS: For the selection of studies, the following
      descriptors were used: "questionarios", "questionnaires", "transtornos de
      degluticao", "deglutition disorders", "programas de rastreamento", and "mass
      screening". The online databases used for the research were Virtual Health
      Library (LILACS, IBECS, MEDLINE, Cochrane Library, SciELO) and PubMed. The
      research was performed from April to June 2013. Selection criteria articles in
      English, Portuguese, and Spanish, regardless of the year of publication, whose
      title, abstract, or text had any relation to the purpose of the research. After
      reading the articles in their entirety, identification data and method of the
      articles were extracted for later analysis. RESULTS: The research carried out
      from the proposed descriptors produced 1,012 articles. After reviewing the
      titles, summaries, and fully reading the articles, 20 studies were chosen. The
      publications on instruments for the identification of dysphagic patients started
      in 1999, and 50% of the analyzed studies were carried out in the USA. The methods
      used on the instruments were questionnaires, observation of patient's clinical
      signals and symptoms, the request for execution of some orofacial movements, and
      swallowing test with water or food. CONCLUSION: Screening instruments in
      dysphagia are fairly heterogeneous and have been developed for different
      audiences with the main objective of identifying patients with swallowing
      disorders.

PMID- 25388066
TI  - Risk factors for proper oral language development in children: a systematic
      literature review.
AB  - PURPOSE: To conduct a systematic review of literature production related to risk
      factors for proper oral language development in children. METHODS: We used the
      terms "child language," "risk factors," and "randomized controlled trial" in
      MEDLINE (accessed via PubMed), Lilacs, SciELO, and The Cochrane Library from
      January 1980 to February 2014. Randomized controlled trials involving the study
      of some risk factors related to child language were included. Works with
      individuals who were not from the age group 0-12 years and presented no reliable
      definition of risk factors were excluded. The research findings were classified
      according to their theme and categorized methodological aspects. RESULTS: We
      observed the lack of a standardized list of risk factors for language available
      for health professionals. The main risk factor mentioned was family dynamics,
      followed by interaction with parents, immediate social environment, and
      encouragement given to the child in the first years of life. It was also observed
      that organic hazards such as brain injury, persistent otitis media, and cardiac
      surgery, besides the type of food and parental counseling, may be related to
      language disorders. CONCLUSION: More randomized controlled trials involving the
      evaluation of risk factors for child language and the creation of further studies
      involving children above 6 years of age and males are needed.

PMID- 25388067
TI  - Impact of inter-judge agreement on perceptual judgment of nasality.
AB  - PURPOSE: To investigate the effect of perceptual inter-judge agreement of
      hypernasality on velopharyngeal (VP) closure prediction. METHODS: Two logistic
      regression models were developed aiming to verify the possibility of predicting
      the VP closure using the following characteristics: rating of VP closure
      (adequate, borderline, inadequate), determined by the pressure-flow technique,
      degree of hypernasality (absent, mild, moderate, severe), and the
      presence/absence of nasal air emission and nasal rustle determined perceptually
      by three experienced speech language pathologists. In the first model, 100 speech
      samples with a moderate agreement rate of hypernasality (kappa coefficient: 0.41)
      were used. In the second model, 43 speech samples with a perfect agreement among
      judges were included. The chi2-test was used to compare the models (p<=0.05).
      RESULTS: In the first model, 65 of the 100 samples were rated in the correct VP
      closure category, with 42 adequate and 23 inadequate. The borderline VP closure
      was not predicted. The second model rated 31 of the 43 samples in the correct
      category, with 21 adequate VP closure, 5 in the borderline VP closure, and 5
      inadequate. There was no difference (p=0.526) between the two models. However,
      the second model showed a higher proportion of accuracy (7%) than the first one,
      and it has also predicted the borderline VP closure. CONCLUSION: These results
      showed the importance of high index of inter-judge agreement when using
      subjective parameters of speech evaluation, especially when compared to an
      instrumental evaluation. This suggests the need for strategies for training and
      calibration of judges in the perceptual judgment to improve the reliability of
      auditory-perceptual assessment.

PMID- 25388068
TI  - Effect of classroom acoustics on the speech intelligibility of students.
AB  - PURPOSE: To analyze the acoustic parameters of classrooms and the relationship
      among equivalent sound pressure level (Leq), reverberation time (T30), the Speech
      Transmission Index (STI), and the performance of students in speech
      intelligibility testing. METHODS: A cross-sectional descriptive study, which
      analyzed the acoustic performance of 18 classrooms in 9 public schools in Belo
      Horizonte, Minas Gerais, Brazil, was conducted. The following acoustic parameters
      were measured: Leq, T30, and the STI. In the schools evaluated, a speech
      intelligibility test was performed on 273 students, 45.4% of whom were boys, with
      an average age of 9.4 years. The results of the speech intelligibility test were
      compared to the values of the acoustic parameters with the help of Student's t
      test. RESULTS: The Leq, T30, and STI tests were conducted in empty and furnished
      classrooms. Children showed better results in speech intelligibility tests
      conducted in classrooms with less noise, a lower T30, and greater STI values. The
      majority of classrooms did not meet the recommended regulatory standards for good
      acoustic performance. CONCLUSION: Acoustic parameters have a direct effect on the
      speech intelligibility of students. Noise contributes to a decrease in their
      understanding of information presented orally, which can lead to negative
      consequences in their education and their social integration as future
      professionals.

PMID- 25388069
TI  - Cortical Auditory Evoked Potential: evaluation of speech detection in adult
      hearing aid users.
AB  - PURPOSE: To analyze the presence of auditory cortical potential and its
      correlation with psychoacoustic detection of speech sounds as well as the latency
      of the P1, N1 e P2 components presented in free field in hearing impaired adults
      with and without amplification. METHODS: We evaluated 22 adults with moderate to
      severe symmetrical bilateral sensorineural hearing loss, regular users of
      bilateral hearing aids. Speech sounds of low (/m/), medium (/g/) and high (/t/)
      frequencies were presented in sound field in decreasing intensities of 75, 65 and
      of 55 dBSPL in free field with and without hearing aids. The used equipment
      performs automatic statistical detection of the presence of response;
      forthermore, the latencies of waves P1, N1 e P2 were labeled and the
      psychoacoustic perception was registered. RESULTS: The results demonstrated the
      increased presence of cortical response with hearing aids. We observed the
      correlation between psychoacoustic perception and automatic detection of 91% for
      the sounds /g/ and /t/ and ranged from 73 to 86% for the sound /m/. The averages
      of latencies P1-P2-N1 decreased with both increasing intensity and the use of
      hearing aids for the three sounds. The differences were significant for the
      sounds /g/ and /t/ in comparison with and without hearing aids. CONCLUSION: There
      was increase in the presence of cortical auditory evoked potential with hearing
      aids. Automatic detection of cortical response provided with hearing aids showed
      91% agreement with the psychoacoustic perception of the speech signal. In the
      analysis of latency measures of the P1, N1 and P2 components, it was observed a
      decrease with the increase of the signal intensity and the use of amplification
      for the three speech stimuli /m/, /g/ and /t/.

PMID- 25388070
TI  - Muscleskeletal pain in dysphonic women.
AB  - OBJECTIVE: To investigate the location, frequency and intensity of muscle pain in
      dysphonic functional/organofunctional women in comparison to women with healthy
      voices. METHODS: Sixty women, ranging in age from 18 to 45 years, divided into
      two groups: Dysphonic Group (DG) - 30 women with functional or organofunctional
      dysphonia; Non-Dysphonic Group (NDG) - 30 women without vocal complaints, and
      with adapted voices. All answered a protocol, marking the localization, frequency
      and intensity symptoms of pain on the temporal area, masseters, submandibular
      areas, larynx/pharynx, front and back of the neck, shoulders, upper back, lower
      back, elbows, fists/hands/fingers, hip/this, knees and ankles/feet. The volunteer
      should report the frequency in which pain was present in the last 12 months: no,
      rarely, frequently or always. The intensity of pain was measured by visual
      analogue scales. The DG and NDG groups were compared using the Mann-Whitney test
      (p<0.05). RESULTS: The women of the DG reported significantly greater frequency
      of submandibular area (p=0.008), laryngeal pain (p<0.001), front of the neck
      (p=0.015), back of the neck (p=0.001), shoulder pain (p=0.027), upper back
      (p=0.027) and also reported significant greater intensity of pain in the
      larynx/pharynx (p=0.022) and back of the neck (p=0.003). CONCLUSION: The
      frequency and intensity of musculoskeletal pain was more frequent and more
      intense in dysphonic women than in women without vocal complaints, showing that
      pain may be related to functional and organofunctional dysphonia in women.

PMID- 25388071
TI  - Severity of voice disorders: integration of perceptual and acoustic data in
      dysphonic patients.
AB  - PURPOSE: To analyze the correlation between acoustic measures and intensity of
      vocal deviation, and its discriminatory power in detecting the presence of vocal
      change, classifying the severity of the deviation and differencing the type of
      predominant voice. METHODS: The sample comprised 186 patients with dysphonia. The
      vocal deviation from the vowel/epsilon/was evaluated by consensus between three
      speech language pathologists, using a Visual Analog Scale. We extracted the mean
      and standard deviation (SD) of the fundamental frequency (F0), jitter, shimmer,
      and Glottal-to-Noise Excitation Ratio (GNE). RESULTS: Mean F0 was negatively
      correlated with the degree of roughness and positively with the degree of
      tension. The F0 SD was positively correlated with the overall, roughness,
      tension, and instability grades. The jitter and shimmer were positively
      correlated with all perceptual parameters. Only the GNE distinguished between
      healthy and dysphonic voices and rated the degree of breathiness. The shimmer
      separated rough voices from not rough voices. The mean F0 was helpful to
      determine the degree of phonatory tension and to separate rough voices from
      breathy and strained voices. CONCLUSION: There is a correlation between the
      acoustic and auditory perceptual measures. The shimmer, the GNE, and F0 SD can be
      used to detect roughness, breathing, and strain, respectively. The GNE and mean
      F0 are useful to classify the degree of breathiness and strain, respectively. The
      mean F0 distinguished between rough, breathy, and strained voices, with rough
      voices more severe compared to the other two.

PMID- 25388072
TI  - Influence of craniomandibular and cervical pain on the activity of masticatory
      muscles in individuals with Temporomandibular Disorder.
AB  - PURPOSE: This study aimed to establish the prevalence of pain in the
      craniomandibular and cervical spine region in individuals with Temporomandibular
      Disorders (TMD) and to analyze the effects of these disorders on the bilateral
      activation of anterior temporalis (AT) and masseter (MA) muscles during the
      masticatory cycle. METHODS: The participants were 55 female volunteers aged 18-30
      years. The presence of TMD and craniomandibular and cervical spine pain was
      evaluated by applying the Research Diagnostic Criteria for Temporomandibular
      Disorders (RDC/TMD) questionnaire and using a combination of tests for the
      cervical region. The muscle activity of AT and MA during the masticatory cycle
      was assessed using the symmetry and antero-posterior coefficient indices.
      RESULTS: The AT activity during the masticatory cycle is more asymmetric in
      individuals with TMD. The craniomandibular pain, more prevalent in these
      individuals, influenced these results. CONCLUSION: Individuals with TMD showed
      changes in the pattern activity of AT. The craniomandibular nociceptive inputs
      can influence the increase in asymmetry of the activation of this muscle.

PMID- 25388073
TI  - Nasalance during use of pharyngeal and glottal place of production.
AB  - PURPOSE: This study obtained nasalance scores during use of compensatory
      articulation (CA) and compared nasalance between groups with and without
      hypernasality and with and without CA. METHODS: Speech samples were obtained from
      43 individuals with and without velopharyngeal dysfunction during repetition of
      20 phrases originating 860 audio recordings and their respective nasometric
      values. After excluding 143 recordings due to low quality, the remaining 717
      samples were rated by three speech language pathologists (SLPs), independently,
      for presence or absence of hypernasality and CA. Nasalance scores for the 553
      samples rated with 100% agreement among the SLPs were grouped according to the
      auditory-perceptual ratings: Group 1 (G1) - included samples without
      hypernasality and without CA (n=191); Group2 (G2) - included samples with
      hypernasality and without CA (n=288); Group 3 (G3) - included samples with
      hypernasality and with pharyngeal fricative (n=33); Group 4 (G4) - included
      samples with hypernasality and with glottal stop (n=41). RESULTS: Analysis of
      variance (ANOVA) revealed significant difference nasalance scores which were
      significantly higher for G2, G3, and G4 (p<0.0001) when compared to G1. The use
      of pharyngeal fricative (G3), particularly during /f/ (p=0.0018) and /s/
      (p=0.0017) productions resulted in nasalance scores significantly higher than
      scores found for G2. CONCLUSION: Significantly higher nasalance values where
      identified during use of pharyngeal fricative.

PMID- 25388074
TI  - Sociocognitive performance in autism spectrum disorders and interference of the
      therapeutic environment.
AB  - PURPOSE: To analyze the sociocognitive performance of children and adolescents
      with autism spectrum disorders in two environments of language therapy, which
      differ as to the physical structure. METHODS: Ten children and adolescents with
      ages between 4 and 13 years, of both genders, diagnosed with autism spectrum
      disorders took part in the study. For data collection, eight filming sessions
      were performed during individual language therapy lasting 30 minutes, being four
      in a room with conventional environmental organization (common room) and four in
      a room with specific ambiance [children's interaction core (CIC) room],
      interspersed during a month. For the analysis of filmed situations, the
      Sociocognitive Performance Protocol was used and obtained data were subjected to
      statistical analysis. RESULTS: No statistical significance was found in
      sociocognitive performance of 10 subjects in the common and CIC rooms, although
      specific differences were observed in some cases. CONCLUSION: The creation of
      preestablished physical environments or specific materials is not and should not
      be considered essential for language therapy. It is noteworthy, however, that the
      absence of a large volume of statistically significant data does not indicate
      that the results are not expressive, reiterating the need for further research in
      the area.

PMID- 25388075
TI  - Inference comprehension during reading: influence of age and education in normal
      adults.
AB  - PURPOSE: To determine the effect of age and education on inferential
      comprehension from written texts in normal individuals. METHODS: A total of 224
      normal adults were stratified into nine groups according to age (young: 18-39
      years, adults: 40-59 years, and elderly: 60-79 years) and educational level (low
      <=4 years, medium: 5-8 years and high >8 years) and were evaluated through the
      battery La gestion de l'implicite (Implicit Information Management Test) to
      determine the ability to make inferences through different types of questions:
      explicit, logical, distractor, pragmatic and others. RESULTS: The elderly showed
      worse performance for total score and distractor questions. Regarding educational
      level, all groups differed on explicit, logical, distractor questions, and on
      total test score. Subjects with high schooling performed better on pragmatic
      inferences and others. CONCLUSION: Age influence on the comprehension of
      inferences may be due to difficulties in attention and executive functions. The
      strong effect of education can be explained by the interaction of inferential
      abilities with other cognitive functions such as working memory, vocabulary span,
      as well as world knowledge.

PMID- 25388076
TI  - Self-perception of people who stutter regarding their experiences and results of
      stuttering treatments.
AB  - PURPOSE: To investigate the opinion about stuttering treatments in people who
      stutter, based on their answers to two open questions. METHODS: The participants
      were 40 adults of both genders, with self-reported stuttering. During the first
      phase of the research, we contacted two Brazilian nongovernmental organizations:
      the Brazilian Stuttering Association (ABRAGAGUEIRA) and the Brazilian Fluency
      Institute (IBF). These associations agreed to participate and were responsible
      for sending the research questions to their members via electronic mail. The
      first contact with the participants elucidated the purpose and method of our
      research and, after obtaining informed consent from participants, the two
      questions were sent. The research questions involved their opinion about cure,
      treatments to which the participants had been submitted, and their outcome.
      RESULTS: After analysis, the answers obtained indicated that people who stutter
      believe in a cure for stuttering; that the ideal therapy would be the one that
      led to the disappearance of the symptoms; and the most frequently reported
      professional to treat the disorder is the speech-language pathologist. The
      results also indicated that although most of the participants had undergone
      speech-language treatment for stuttering, neither significant improvements were
      observed nor satisfaction was positive. CONCLUSION: The results indicate that the
      answers presented by the participants were not based on scientific knowledge
      about the disorder but on their wish that "something could happen" to make
      stuttering "disappear." Although in this study we did not investigate the type of
      treatment to which the patients were submitted, the results suggest that the
      factors that contribute to an effective treatment are contentious.

PMID- 25388077
TI  - Laryngeal cleft type I in neonate: case report.
AB  - Laryngeal cleft (LC) is a congenital malformation that leads to the unusual
      communication between the esophagus and the laryngotracheal complex. It is a rare
      disease, mostly prevalent among male individuals. The goal of this study was to
      describe the evaluation and intervention by the speech language pathologist of a
      female newborn diagnosed with LC type I, admitted on the University Hospital of
      Universidade de Sao Paulo, in her second hospitalization due to small weight gain
      and pneumonia. She was submitted to a bedside clinical evaluation of the
      swallowing and the most important occurrence was frequent gagging. The
      videofluoroscopy swallowing study showed laryngotracheal aspiration level 8 for
      thin liquid and level 1 for thickened liquid, according to the Penetration
      Aspiration Scale. The newborn was submitted to a microlaryngoscopy, in which the
      presence of LC type I was found. After the diagnosis, the speech language
      pathologist offered thickened liquid at 6% and, in 8 days, the newborn was
      discharged with exclusive oral diet without gagging. Eight outpatient
      consultations were carried out for 11 months, with emphasis on reintroduction of
      thin liquids. The treatment was discontinued and the patient was put on general
      diet for the age without modifications. Throughout follow-up, the patient
      remained asymptomatic and showed no respiratory complications. 

PMID- 25388079
TI  - Ratiometric time-gated luminescence probe for hydrogen sulfide based on
      lanthanide complexes.
AB  - Developments of ratiometric bioprobes are highly appealing due to the superiority
      of their self-calibration capability for the quantitative biotracking. In this
      work, we designed and synthesized a novel lanthanide complex-based ratiometric
      luminescence probe, [4'-(2,4-dinitrophenyloxy)-2,2':6',2"-terpyridine-6,6"
      diyl]bis(methylenenitrilo) tetrakis(acetate)-Eu(3+)/Tb(3+) (NPTTA-Eu(3+)/Tb(3+)),
      for the specific recognition and quantitative time-gated luminescence detection
      of hydrogen sulfide (H2S) in aqueous and living cell samples. Due to the presence
      of the photoinduced electron transfer (PET) process from the terpyridine
      Eu(3+)/Tb(3+) moiety to 2,4-dinitrophenyl (DNP), the probe itself is weakly
      luminescent. In physiological pH aqueous media, the reaction of NPTTA
      Eu(3+)/Tb(3+) with H2S leads to the cleavage of DNP moiety from the probe
      molecule, which affords the deprotonated (4'-hydroxy-2,2':6',2"-terpyridine-6,6"
      diyl)bis(methylenenitrilo) tetrakis(acetate)-Eu(3+)/Tb(3+) and terminates the PET
      process. Meanwhile, the intensity of Tb(3+) emission at 540 nm is remarkably
      increased, while that of the Eu(3+) emission at 610 nm is slightly decreased.
      After the reaction, the intensity ratio of Tb(3+) emission to Eu(3+) emission,
      I540/I610, was ~220-fold increased, and the dose-dependent enhancement of
      I540/I610 showed a good linearity upon the increase of H2S concentration with a
      detection limit of 3.5 nM. This unique luminescence response allowed NPTTA
      Eu(3+)/Tb(3+) to be conveniently used as a ratiometric probe for the time-gated
      luminescence detection of H2S with I540/I610 as a signal. In addition, the
      applicability of the probe for the quantitative time-gated luminescence imaging
      of intracellular H2S in living cells was investigated. The results demonstrated
      the efficacy and advantage of the new probe for the time-gated luminescence cell
      imaging application. 

PMID- 25388080
TI  - Development of unique xanthene-cyanine fused near-infrared fluorescent
      fluorophores with superior chemical stability for biological fluorescence
      imaging.
AB  - The development of near-infrared (NIR) functional fluorescent dyes has gained
      increasing attention over the last few decades. Herein, we describe the
      development of a unique type of xanthene-cyanine fused NIR fluorophores, XC dyes,
      formed by reacting chloro-substituted cyanine with resorcin or its analogues
      under anhydrous conditions. XC dyes are a hybrid of cyanine and xanthene. The
      preliminary mechanistic studies indicate that the formation of XC compounds
      likely includes a sequence of cyclization and oxidation. XC dyes have absorption
      and emission in the NIR region, and their fluorescence properties can be
      controlled by modifications of the key hydroxyl and amine groups. The novel XC
      NIR dyes are advantageous over previously developed merocyanine dyes NIR dyes in
      their chemical stability against strong nucleophiles. Quantum chemical
      calculations reveal that the distinct properties of XC and HD dyes can be
      attributed to their structural differences. By taking advantage of the superior
      properties of XC dyes, we have further constructed a new NIR fluorescent probe,
      XC-H2 S, which is capable of monitoring both the concentration- and time
      dependent variations of H2 S in living animals, highlighting the value of XC NIR
      dyes. We expect that the unique XC NIR dyes developed herein will find broader
      applications than HD NIR dyes as fluorescent platforms for the development of a
      wide variety of NIR fluorescent probes, in particular, those suitable for targets
      of interest that have strong nucleophilic character. 

PMID- 25388081
TI  - Fatty acid compositions of triglycerides and free fatty acids in sebum depend on
      amount of triglycerides, and do not differ in presence or absence of acne
      vulgaris.
AB  - To clarify the influence of the fatty acid composition of sebum in acne vulgaris,
      we investigated the amounts and fatty acid compositions of triglycerides (TG) and
      free fatty acids (FFA), and the amounts of cutaneous superficial
      Propionibacterium acnes in acne patients and healthy subjects. The foreheads of
      18 female patients, 10 male patients, 10 healthy females and 10 healthy males
      were studied in a Japanese population. There were significant differences in the
      amounts of sebum, TG and cutaneous superficial P. acnes, as well as the fatty
      acid compositions of TG and FFA between acne patients and healthy subjects in
      females. Their fatty acid compositions were correlated with the amount of TG with
      or without acne. It was clarified that the fatty acid compositions of TG and FFA
      depended on the amount of TG, and there were no differences in the fatty acid
      composition in the presence and absence of acne. 

PMID- 25388082
TI  - Scale-free brain dynamics under physical and psychological distress: pre
      treatment effects in women diagnosed with breast cancer.
AB  - Stressful life events are related to negative outcomes, including physical and
      psychological manifestations of distress, and behavioral deficits. Patients
      diagnosed with breast cancer report impaired attention and working memory prior
      to adjuvant therapy, which may be induced by distress. In this article, we
      examine whether brain dynamics show systematic changes due to the distress
      associated with cancer diagnosis. We hypothesized that impaired working memory is
      associated with suppression of "long-memory" neuronal dynamics; we tested this by
      measuring scale-free ("fractal") brain dynamics, quantified by the Hurst exponent
      (H). Fractal scaling refers to signals that do not occur at a specific time
      scale, possessing a spectral power curve P(f)? f(-beta); they are "long-memory"
      processes, with significant autocorrelations. In a BOLD functional magnetic
      resonance imaging study, we scanned three groups during a working memory task:
      women scheduled to receive chemotherapy or radiotherapy and aged-matched
      controls. Surprisingly, patients' BOLD signal exhibited greater H with increasing
      intensity of anticipated treatment. However, an analysis of H and functional
      connectivity against self-reported measures of psychological distress (Worry,
      Anxiety, Depression) and physical distress (Fatigue, Sleep problems) revealed
      significant interactions. The modulation of (Worry, Anxiety) versus (Fatigue,
      Sleep Problems, Depression) showed the strongest effect, where higher worry and
      lower fatigue was related to reduced H in regions involved in visuospatial
      search, attention, and memory processing. This is also linked to decreased
      functional connectivity in these brain regions. Our results indicate that the
      distress associated with cancer diagnosis alters BOLD scaling, and H is a
      sensitive measure of the interaction between psychological versus physical
      distress.

PMID- 25388084
TI  - Hypereosinophilic syndrome as a cause of fatal thrombosis: two case reports with
      histological study.
AB  - Herein we present two cases of hypereosinophilic syndrome with a unique clinical
      presentation. One patient showed severe systemic thrombosis with splenic rupture
      and the other patient showed finger gangrene with various systemic symptoms. Both
      patients were examined histologically, and several characteristics were noted.
      First, fresh or organized thrombosis with marked eosinophilic infiltration was
      observed in the cavity and walls of the thrombosed vessels. Second, many
      eosinophils showed degranulation and were positive for eosinophilic cationic
      protein on immunohistological examination. Third, the structures of thrombosed
      vessels were well preserved, which is not observed in systemic vasculitis. These
      patients exhibited no neoplastic features and were treated with prednisolone with
      excellent therapeutic results. 

PMID- 25388083
TI  - Haemostatic risk factors in dyslipidemic rabbits: role of 10-dehydrogingerdione
      as a new hypolipemic agent.
AB  - Micro and macrovascular complications occurring during hyperlipidemia are mostly
      attributed to haemostatic impairment and vascular endothelial dysfunction.
      Cholesteryl ester transfer protein (CETP) inhibitors have been emerged recently
      as promising hypocholesterolemic agents to confer protection against lipid
      mediated atherosclerosis. Therefore, 10-dehydrogingerdione (DHGD), a novel CETP
      inhibitor isolated from ginger rhizomes, was selected as a natural product in the
      present study to illustrate its effect on haemostatic impairment associated with
      hyperlipidemia as compared to a currently used hypocholesterolemic agent,
      atorvastatin (ATOR). Rabbits were fed a high cholesterol diet (HCD) and divided
      into three groups. One group served as control group while the other groups
      received DHGD or ATOR. Dyslipidemic rabbits showed a significant increase in
      serum endothelin-1, ischemia modified albumin, plasminogen activator inhibitor-1,
      prothrombin fragments (1+2) and plasma fibrinogen along with a decrease of nitric
      oxide level in serum. Daily administration of ATOR or DHGD significantly
      decreased the aforementioned coagulation and ischemia biomarkers and increased
      serum nitric oxide. DHGD (natural) results seem to be more remarkable as compared
      to ATOR (synthetic). 

PMID- 25388085
TI  - [Current treatment options with artificial corneas: Boston Kpro, Osteo
      odontokeratoprosthesis, Miro Cornea(r) and KeraKlear(r)].
AB  - BACKGROUND: Although corneal transplant surgery in avascular normal risk eyes is
      becoming even more minimally invasive and successful, treatment options for
      difficult to treat patients with high risk eyes are still limited. In these cases
      HLA typed allogeneic transplants and artificial corneas (keratoprostheses) can be
      used. METHODS: This article combines a review of the literature in PubMed and own
      clinical experiences on the use of artificial corneas in high risk eyes. Osteo
      odontokeratoprosthesis (OOKP), Boston Kpro, Miro Cornea(r) and KeraKlear(r)
      corneas were used as clinical keratoprostheses. RESULTS: Worldwide, the most
      experience exists for the use of Boston Kpro and OOKP in high risk eyes. Miro
      Cornea(r) and KeraKlear(r) are new procedures where only preliminary results are
      available and further evaluation is necessary. The longest experience and best
      anatomical long-term results have been achieved with OOKPs. Comparable cohorts
      are available for the Boston Kpro. The function of all keratoprostheses is
      threatened by secondary glaucoma. Implantation of the KeraKlear(r) prosthesis
      remains difficult. The Miro Cornea(r) shows an initially stable integration
      behavior. CONCLUSION: Keratoprostheses, such as the Boston Kpro and OOKP are
      valid treatment options for eyes which are not open to therapy with allogeneic
      corneal transplantation. Modern implants such as KeraKlear(r) prosthesis and Miro
      Cornea(r) need further prospective clinical evaluation.

PMID- 25388086
TI  - [New possibilities for ocular surface reconstruction: collagen membranes and
      biocompatible elastomer nanofibers].
AB  - BACKGROUND: Amniotic membranes have been used for many years for reconstruction
      of the ocular surface. Despite having anti-inflammatory and antiangiogenic
      properties as well as being suitable as a carrier for corneal epithelial cells,
      amniotic membranes also have some limitations for use at the human cornea:
      availability is limited, there are major interindividual variations in structure
      and growth factor content and are not free from the risk of disease transmission.
      Progress in tissue engineering has been made aiming at the development and
      improvement of alternative biomaterials. OBJECTIVES: This article presents new
      approaches for reconstruction of the corneal surface with collagen-based
      biomaterials and polymers. MATERIAL AND METHODS: Electronic databases were
      searched for articles which evaluated collagenous biomaterials for use at the
      corneal surface. In addition the authors' own experiences with novel biomaterials
      are described. RESULTS: In vitro evaluation of the described biomaterials
      suggested a high biocompatibility with corneal epithelial cells in cell cultures.
      In vivo experiments with these materials in animal corneas demonstrated a certain
      variability in degradation and remodeling. Although some materials showed
      promising experimental results none of these are established in the clinical
      routine and only few clinical studies have so far been conducted with collagen
      based biomaterials. CONCLUSION: Although the majority of the described
      biomaterials are currently still in the experimental stage, a transfer into the
      clinical routine is conceivable and of great therapeutic interest.

PMID- 25388087
TI  - Study of sequential dexter energy transfer in high efficient phosphorescent white
      organic light-emitting diodes with single emissive layer.
AB  - In this study, we report our effort to realize high performance single emissive
      layer three color white phosphorescent organic light emitting diodes (PHOLEDs)
      through sequential Dexter energy transfer of blue, green and red dopants. The
      PHOLEDs had a structure of; ITO(1500 A)/NPB(700 A)/mCP:Firpic-x%:Ir(ppy)3
      0.5%:Ir(piq)3-y%(300 A)/TPBi(300 A)/Liq(20 A)/Al(1200 A). The dopant
      concentrations of FIrpic, Ir(ppy)3 and Ir(piq)3 were adjusted and optimized to
      facilitate the preferred energy transfer processes attaining both the best
      luminous efficiency and CIE color coordinates. The presence of a deep trapping
      center for charge carriers in the emissive layer was confirmed by the observed
      red shift in electroluminescent spectra. White PHOLEDs, with phosphorescent
      dopant concentrations of FIrpic-8.0%:Ir(ppy)3-0.5%:Ir(piq)3-0.5% in the mCP host
      of the single emissive layer, had a maximum luminescence of 37,810 cd/m(2) at 11
      V and a luminous efficiency of 48.10 cd/A at 5 V with CIE color coordinates of
      (0.35, 0.41).

PMID- 25388088
TI  - Potential mechanisms for cell-based gene therapy to treat HIV/AIDS.
AB  - INTRODUCTION: An estimated 35 million people are infected with HIV worldwide.
      Anti-retroviral therapy (ART) has reduced the morbidity and mortality of HIV
      infected patients but efficacy requires strict adherence and the treatment is not
      curative. Most importantly, the emergence of drug-resistant virus strains and
      drug toxicity can restrict the long-term therapeutic efficacy in some patients.
      Therefore, novel treatment strategies that permanently control or eliminate the
      virus and restore the damaged immune system are required. Gene therapy against
      HIV infection has been the topic of intense investigations for the last two
      decades because it can theoretically provide such a durable anti-HIV control.
      AREAS COVERED: In this review we discuss two major gene therapy strategies to
      combat HIV. One approach aims to kill HIV-infected cells and the other is based
      on the protection of cells from HIV infection. We discuss the underlying
      molecular mechanisms for candidate approaches to permanently block HIV infection,
      including the latest strategies and future therapeutic applications. EXPERT
      OPINION: Hematopoietic stem cell-based gene therapy for HIV/AIDS may eventually
      become an alternative for standard ART and should ideally provide a functional
      cure in which the virus is durably controlled without medication. Recent results
      from preclinical research and early-stage clinical trials support the feasibility
      and safety of this novel strategy.

PMID- 25388090
TI  - Phonon-drag thermopower in a monolayer MoS2.
AB  - The theory of phonon-drag thermopower S(g) is developed in a monolayer MoS(2),
      considering the electron-acoustic phonon interaction via deformation potential
      (DP) and piezoelectric (PE) coupling, as a function of temperature T and electron
      concentration n(s). DP coupling of TA (LA) phonons is taken to be unscreened
      (screened) and PE coupling of LA and TA phonons is taken to be screened. S(g) due
      to DP coupling of TA phonons is found to be dominant over all other mechanisms
      and in the Bloch-Gruneisen regime it gives power law S(g) ~ T3. All other
      mechanisms give S(g) ~ T(5). These power laws are characteristic of two
      dimensional (2D) phonons with linear dispersion. Screening enhances the exponent
      of T by 2 and strongly suppresses S(g) due to the large effective mass of the
      electrons. We find that S(g), due to screened DP and PE couplings is nearly the
      same in contrast to the results in GaAs heterojunctions. Also, we predict that
      S(g) ~ n(s)(-3/2), a characteristic of 2D electrons with parabolic relation. With
      the increasing (decreasing) T(n(s)) its exponent decreases. For comparison, we
      give diffusion thermopower S(d). At very low T and high n(s), S(d) ~ T and n(2)(
      1). S(d) is found to be greater than S(g) for about T < 2-3 K. The results are
      compared with those in conventional 2D electron gas and graphene.

PMID- 25388091
TI  - Solid state effects on the electronic structure of H2OEP.
AB  - We present the results of a joint experimental and theoretical investigation
      concerning the effect of crystal packing on the electronic properties of the
      H2OEP molecule. Thin films, deposited in ultra high vacuum on metal surfaces, are
      investigated by combining valence band photoemission, inverse photoemission, and
      X-ray absorption spectroscopy. The spectra of the films are compared, when
      possible, with those measured in the gas phase. Once many-body effects are
      included in the calculations through the GW method, the electronic structure of
      H2OEP in the film and gas phase are accurately reproduced for both valence and
      conduction states. Upon going from an isolated molecule to the film phase, the
      electronic gap shrinks significantly and the lowest unoccupied molecular orbital
      (LUMO) and LUMO + 1 degeneracy is removed. The calculations show that the
      reduction of the transport gap in the film is entirely addressable to the
      enhancement of the electronic screening. 

PMID- 25388089
TI  - Global gene expression profiling in R155H knock-in murine model of VCP disease.
AB  - Dominant mutations in the valosin-containing protein (VCP) gene cause inclusion
      body myopathy associated with Paget disease of bone and frontotemporal dementia,
      which is characterized by progressive muscle weakness, dysfunction in bone
      remodeling, and frontotemporal dementia. More recently, VCP has been linked to 2%
      of familial amyotrophic lateral sclerosis cases. VCP plays a significant role in
      a plethora of cellular functions including membrane fusion, transcription
      activation, nuclear envelope reconstruction, postmitotic organelle reassembly,
      and cell cycle control. To elucidate the pathological mechanisms underlying the
      VCP disease progression, we have previously generated a VCP(R155H/+) mouse model
      with the R155H mutation. Histological analyses of mutant muscle showed
      vacuolization of myofibrils, centrally located nuclei, and disorganized muscle
      fibers. Global expression profiling of VCP(R155H/+) mice using gene annotations
      by DAVID identified key dysregulated signaling pathways including genes involved
      in the physiological system development and function, diseases and disorders, and
      molecular and cellular functions. There were a total of 212 significantly
      dysregulated genes, several of which are involved in the regulation of
      proteasomal function and NF-kappaB signaling cascade. Findings of the gene
      expression study were validated by using quantitative reverse transcriptase
      polymerase chain reaction analyses to test genes involved in various signaling
      cascades. This investigation reveals the importance of the VCP(R155H/+) mouse
      model in the understanding of cellular and molecular mechanisms causing VCP
      associated neurodegenerative diseases and in the discovery of novel therapeutic
      advancements and strategies for patients suffering with these debilitating
      disorders. 

PMID- 25388092
TI  - Isomeric product detection in the heterogeneous reaction of hydroxyl radicals
      with aerosol composed of branched and linear unsaturated organic molecules.
AB  - The influence of molecular structure (branched vs linear) on product formation in
      the heterogeneous oxidation of unsaturated organic aerosol is investigated.
      Particle phase product isomers formed from the reaction of squalene (C30H50, a
      branched alkene with six C?C double bonds) and linolenic acid (C18H30O2, a linear
      carboxylic acid with three C?C double bonds) with OH radicals are identified and
      quantified using two-dimensional gas chromatography-mass spectrometry. The
      reactions are measured at low and high [O2] (~1% vs 10% [O2]) to understand the
      roles of hydroxyalkyl and hydroxyperoxy radical intermediates in product
      formation. A key reaction step is OH addition to a C?C double bond to form a
      hydroxyalkyl radical. In addition, allylic alkyl radicals, formed from H atom
      abstraction reactions by hydroxyalkyl or OH radicals play important roles in the
      chemistry of product formation. Functionalization products dominate the squalene
      reaction at ~1% [O2], with the total abundance of observed functionalization
      products being approximately equal to the fragmentation products at 10% [O2]. The
      large abundance of squalene fragmentation products at 10% [O2] is attributed to
      the formation and dissociation of tertiary hydroxyalkoxy radical intermediates.
      For linolenic acid aerosol, the formation of functionalization products dominates
      the reaction at both ~1% and 10% [O2], suggesting that the formation and
      dissociation of secondary hydroxyalkoxy radicals are minor reaction channels for
      linear molecules. The distribution of linolenic acid functionalization products
      depends upon [O2], indicating that O2 controls the reaction pathways of the
      secondary hydroxyalkyl radical. For both reactions, alcohols are formed in favor
      of carbonyl functional groups, suggesting that there are some key differences
      between heterogeneous reactions involving allylic radical intermediates and those
      reactions of OH radicals with simple saturated hydrocarbons. 

PMID- 25388093
TI  - Tools for T-RFLP data analysis using Excel.
AB  - BACKGROUND: Terminal restriction fragment length polymorphism (T-RFLP) analysis
      is a DNA-fingerprinting method that can be used for comparisons of the microbial
      community composition in a large number of samples. There is no consensus on how
      T-RFLP data should be treated and analyzed before comparisons between samples are
      made, and several different approaches have been proposed in the literature. The
      analysis of T-RFLP data can be cumbersome and time-consuming, and for large
      datasets manual data analysis is not feasible. The currently available tools for
      automated T-RFLP analysis, although valuable, offer little flexibility, and few,
      if any, options regarding what methods to use. To enable comparisons and
      combinations of different data treatment methods an analysis template and an
      extensive collection of macros for T-RFLP data analysis using Microsoft Excel
      were developed. RESULTS: The Tools for T-RFLP data analysis template provides
      procedures for the analysis of large T-RFLP datasets including application of a
      noise baseline threshold and setting of the analysis range, normalization and
      alignment of replicate profiles, generation of consensus profiles, normalization
      and alignment of consensus profiles and final analysis of the samples including
      calculation of association coefficients and diversity index. The procedures are
      designed so that in all analysis steps, from the initial preparation of the data
      to the final comparison of the samples, there are various different options
      available. The parameters regarding analysis range, noise baseline, T-RF
      alignment and generation of consensus profiles are all given by the user and
      several different methods are available for normalization of the T-RF profiles.
      In each step, the user can also choose to base the calculations on either peak
      height data or peak area data. CONCLUSIONS: The Tools for T-RFLP data analysis
      template enables an objective and flexible analysis of large T-RFLP datasets in a
      widely used spreadsheet application.

PMID- 25388094
TI  - In response to Vascularized tissue to reduce fistula following salvage total
      laryngectomy: a systematic review.

PMID- 25388095
TI  - Congenital adrenal hyperplasia presenting as a large adrenal incidentaloma in an
      elderly man.

PMID- 25388096
TI  - Linewidth pressure measurement: a new technique for high vacuum characterization.
AB  - Pressure measurement is often the limiting factor in the accuracy of quantitative
      ion-molecule experiments. We present a new method for pressure measurement based
      on analysis of pressure-limited Fourier transform ion cyclotron resonance (FTICR)
      linewidths for well-characterized collisions of Ar(+) with Ar. The kinetic energy
      dependence of Ar(+)/Ar collision cross sections is well-described using a single
      parameter fitting procedure, which results in pressure measurements in good
      agreement with those from a cold cathode tube and from measurement of total ion
      signal following electron impact ionization. The new method avoids problems
      inherent in ionization-based methods, such as those arising from differences in
      ionization potential or perturbations to the pressure that occur during electron
      ionization of the gas to be measured, and should be applicable in the trapping
      cells of FTICR and Orbitrap mass spectrometers. 

PMID- 25388097
TI  - Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for
      pancreatic cancer diagnosis increases sensitivity and specificity.
AB  - Late diagnosis contributes to pancreatic cancer (PaCa) dismal prognosis, urging
      for reliable, early detection. Serum-exosome protein and/or miRNA markers might
      be suitable candidates, which we controlled for patients with PaCa. Protein
      markers were selected according to expression in exosomes of PaCa cell line
      culture supernatants, but not healthy donors' serum-exosomes. miRNA was selected
      according to abundant recovery in microarrays of patients with PaCa, but not
      healthy donors' serum-exosomes and exosome-depleted serum. According to these
      preselections, serum-exosomes were tested by flow cytometry for the PaCa
      initiating cell (PaCIC) markers CD44v6, Tspan8, EpCAM, MET and CD104. Serum
      exosomes and exosome-depleted serum was tested for miR-1246, miR-4644, miR-3976
      and miR-4306 recovery by qRT-PCR. The majority (95%) of patients with PaCa (131)
      and patients with nonPa-malignancies reacted with a panel of anti-CD44v6, 
      Tspan8, -EpCAM and -CD104. Serum-exosomes of healthy donors' and patients with
      nonmalignant diseases were not reactive. Recovery was tumor grading and staging
      independent including early stages. The selected miR-1246, miR-4644, miR-3976 and
      miR-4306 were significantly upregulated in 83% of PaCa serum-exosomes, but rarely
      in control groups. These miRNA were also elevated in exosome-depleted serum of
      patients with PaCa, but at a low level. Concomitant evaluation of PaCIC and miRNA
      serum-exosome marker panels significantly improved sensitivity (1.00, CI: 0.95-1)
      with a specificity of 0.80 (CI: 0.67-0.90) for PaCa versus all others groups and
      of 0.93 (CI: 0.81-0.98) excluding nonPa-malignancies. Thus, the concomitant
      evaluation of PaCIC and PaCa-related miRNA marker panels awaits retrospective
      analyses of larger cohorts, as it should allow for a highly sensitive, minimally
      invasive PaCa diagnostics. 

PMID- 25388098
TI  - Stress responses as determinants of antimicrobial resistance in Pseudomonas
      aeruginosa: multidrug efflux and more.
AB  - Pseudomonas aeruginosa is a notoriously antimicrobial-resistant organism that is
      increasingly refractory to antimicrobial chemotherapy. While the usual array of
      acquired resistance mechanisms contribute to resistance development in this
      organism a multitude of endogenous genes also play a role. These include a
      variety of multidrug efflux loci that contribute to both intrinsic and acquired
      antimicrobial resistance. Despite their roles in resistance, however, it is clear
      that these efflux systems function in more than just antimicrobial efflux.
      Indeed, recent data indicate that they are recruited in response to environmental
      stress and, therefore, function as components of the organism's stress responses.
      In fact, a number of endogenous resistance-promoting genes are linked to
      environmental stress, functioning as part of known stress responses or recruited
      in response to a variety of environmental stress stimuli. Stress responses are,
      thus, important determinants of antimicrobial resistance in P. aeruginosa. As
      such, they represent possible therapeutic targets in countering antimicrobial
      resistance in this organism.

PMID- 25388099
TI  - Clinical safety and effectiveness of collagenase clostridium histolyticum
      injection in patients with Peyronie's disease: a phase 3 open-label study.
AB  - INTRODUCTION: Collagenase clostridium histolyticum (CCH; Xiaflex, Auxilium
      Pharmaceuticals, Inc., Chesterbrook, PA, USA) is a Food and Drug Administration
      approved, intralesional treatment for Peyronie's disease (PD). AIM: The aim of
      this study was to assess the safety and effectiveness of CCH in the treatment of
      PD. METHODS: This phase 3, open-label study enrolled subjects who were CCH-naive,
      were enrolled in a previous pharmacokinetic study, or had received placebo in an
      earlier phase 2 CCH study. Each treatment cycle included two intralesional
      injections of CCH 0.58 mg, approximately 24-72 hours apart, and plaque modeling
      24-72 hours after the second injection of each cycle. The treatment cycle was
      repeated after 6 weeks for <=4 treatment cycles. MAIN OUTCOME MEASURES: The co
      primary end points were the mean percent change in penile curvature deformity and
      the mean improvement in PD bother score (range 0-16) from baseline to week 36.
      RESULTS: Of the 347 subjects treated with >=1 injection, 238 had both a penile
      curvature measurement and a Peyronie's Disease Questionnaire response at baseline
      and >=1 subsequent time point. Mean baseline penile curvature deformity was 53.0
      degrees  and mean PD symptom bother was 7.3. Statistically significant mean
      improvements from baseline to week 36 were observed in both penile curvature
      deformity (34.4% [95% confidence interval {CI}, 31.2%, 37.6%]) and PD symptom
      bother score (3.3 [95% CI, 2.8, 3.7]). Most adverse events (AEs) were mild or
      moderate in severity and local to the penis. There were three serious treatment
      related AEs, two penile hematomas and one corporal rupture; all resolved with
      treatment. CONCLUSIONS: Potentially clinically meaningful and statistically
      significant improvements in penile curvature deformity and PD symptom bother
      scores were observed with intralesional injection of CCH compared with baseline
      in men with PD. CCH was generally well tolerated, with AEs primarily transient
      and local to injection site. In conjunction with previous studies, the results of
      this open-label study support the use of CCH in the treatment of PD.

PMID- 25388100
TI  - Tracheal reconstruction using composite nasal septal graft in patients with
      invasive thyroid carcinoma.
AB  - OBJECTIVE: This paper presents a series of three patients who were identified as
      having partial thickness involvement of the laryngotracheal complex secondary to
      invasive, well-differentiated thyroid cancer. These patients were managed with
      full thickness window resection and reconstruction using a composite nasal septal
      graft. METHODS: A review of the Princess Alexandra Hospital database (comprising
      prospectively collated data) was undertaken to identify patients who had
      undergone full thickness tracheal resection and reconstruction using a composite
      nasal septal graft; demographic, operative technique and survival outcome data
      were collated. RESULTS: Three patients had a composite nasal septal graft
      performed for reconstruction of full thickness laryngotracheal defects following
      the excision of well-differentiated thyroid cancer. There were no cases of local
      recurrence after a minimum of 18 months' follow up. CONCLUSION: This paper
      describes our surgical technique for reconstruction of these defects using a
      composite nasal septal graft. It also presents data on our three cases to date,
      in which the technique has been used safely. A discussion of the surgical
      management of locally invasive, well-differentiated thyroid cancer is provided.

PMID- 25388101
TI  - CD109 is specifically expressed in endothelial cells of cutaneous cavernous
      haemangioma.

PMID- 25388102
TI  - Silicon nanofin grating as a miniature chirality-distinguishing beam-splitter.
AB  - The polarization of light plays a central role in its interaction with matter, in
      situations ranging from familiar (for example, reflection and transmission at an
      interface) to sophisticated (for example, nonlinear optics). Polarization control
      is therefore pivotal for many optical systems, and achieved using bulk devices
      such as wave-plates and beam-splitters. The move towards optical system
      miniaturization therefore motivates the development of micro- and nanostructures
      for polarization control. For such control to be complete, one must distinguish
      not only between linear polarizations, but also between left- and right-circular
      polarizations. Some previous works used surface plasmons to this end, but these
      are inherently lossy. Other works used complex-layered structures. Here we
      demonstrate a planar dielectric chirality-distinguishing beam-splitter. The beam
      splitter consists of amorphous silicon nanofins on a glass substrate and deflects
      left- and right-circularly polarized beams into different directions. Contrary to
      intuitive expectations, we utilize an achiral architecture to realize a chiral
      beam-splitting functionality. 

PMID- 25388104
TI  - Cutaneous paraneoplastic granulomatous eruptions secondary to metastatic
      carcinoid tumour.

PMID- 25388103
TI  - Expression of certain leukemia/lymphoma related microRNAs and its correlation
      with prognosis in childhood acute lymphoblastic leukemia.
AB  - In spite of the improved efficacy of therapy, it still fails in 15-20 % of
      childhood acute lymphoblastic leukemia (ALL) patients. Recently, altered
      expression of certain miRNAs (miRs) have been described in ALL with potential
      effect on prognosis. Presence of certain miRs (miRNA-16, -21, -24, -29b, -128b, 
      142-3p, -155, -223) was characterized in human lymphoma and leukemia cells by
      real-time PCR. Expression of miRs in pediatric ALL patients (n = 24) was measured
      before chemotherapy, at conventional response checkpoints and at relapse.
      Correlation between altered miR expression and response to prednisolone at day 8
      of therapy and long term prognosis was statistically analysed. Overexpression of
      "oncomiR/inflammamiR"-21 - which is characteristic in different tumors-was
      missing in human ALL cells. However, higher expression of miR-128b and lower
      expression of miR-223 is generally characteristic for human ALL cell lines and
      ALL cells isolated from pediatric patients. Correlation was shown between miR
      128b expression and prognosis, prednisolone response and survival data in
      childhood ALL. Expression of miR-128b and miR-223-both are leukemia specific
      changed in parallel with percentage of bone marrow blasts in remission and during
      relapse. Therefore, we suggest that overexpression of miR-128b and downregulation
      of miR-223 shows a significant correlation with treatment response and prognosis
      in childhood ALL.

PMID- 25388105
TI  - The Eukaryotic Pathogen Databases: a functional genomic resource integrating data
      from human and veterinary parasites.
AB  - Over the past 20 years, advances in high-throughput biological techniques and the
      availability of computational resources including fast Internet access have
      resulted in an explosion of large genome-scale data sets "big data." While such
      data are readily available for download and personal use and analysis from a
      variety of repositories, often such analysis requires access to seldom-available
      computational skills. As a result a number of databases have emerged to provide
      scientists with online tools enabling the interrogation of data without the need
      for sophisticated computational skills beyond basic knowledge of Internet browser
      utility. This chapter focuses on the Eukaryotic Pathogen Databases (EuPathDB:
      http://eupathdb.org) Bioinformatic Resource Center (BRC) and illustrates some of
      the available tools and methods.

PMID- 25388106
TI  - From sequence mapping to genome assemblies.
AB  - The development of "next-generation" high-throughput sequencing technologies has
      made it possible for many labs to undertake sequencing-based research projects
      that were unthinkable just a few years ago. Although the scientific applications
      are diverse, e.g., new genome projects, gene expression analysis, genome-wide
      functional screens, or epigenetics-the sequence data are usually processed in one
      of two ways: sequence reads are either mapped to an existing reference sequence,
      or they are built into a new sequence ("de novo assembly"). In this chapter, we
      first discuss some limitations of the mapping process and how these may be
      overcome through local sequence assembly. We then introduce the concept of de
      novo assembly and describe essential assembly improvement procedures such as
      scaffolding, contig ordering, gap closure, error evaluation, gene annotation
      transfer and ab initio gene annotation. The results are high-quality draft
      assemblies that will facilitate informative downstream analyses. 

PMID- 25388107
TI  - Sequencing and annotation of mitochondrial genomes from individual parasitic
      helminths.
AB  - Mitochondrial (mt) genomics has significant implications in a range of
      fundamental areas of parasitology, including evolution, systematics, and
      population genetics as well as explorations of mt biochemistry, physiology, and
      function. Mt genomes also provide a rich source of markers to aid molecular
      epidemiological and ecological studies of key parasites. However, there is still
      a paucity of information on mt genomes for many metazoan organisms, particularly
      parasitic helminths, which has often related to challenges linked to sequencing
      from tiny amounts of material. The advent of next-generation sequencing (NGS)
      technologies has paved the way for low cost, high-throughput mt genomic research,
      but there have been obstacles, particularly in relation to post-sequencing
      assembly and analyses of large datasets. In this chapter, we describe protocols
      for the efficient amplification and sequencing of mt genomes from small portions
      of individual helminths, and highlight the utility of NGS platforms to expedite
      mt genomics. In addition, we recommend approaches for manual or semi-automated
      bioinformatic annotation and analyses to overcome the bioinformatic "bottleneck"
      to research in this area. Taken together, these approaches have demonstrated
      applicability to a range of parasites and provide prospects for using complete mt
      genomic sequence datasets for large-scale molecular systematic and
      epidemiological studies. In addition, these methods have broader utility and
      might be readily adapted to a range of other medium-sized molecular regions
      (i.e., 10-100 kb), including large genomic operons, and other organellar (e.g.,
      plastid) and viral genomes. 

PMID- 25388108
TI  - A beginners guide to estimating the non-synonymous to synonymous rate ratio of
      all protein-coding genes in a genome.
AB  - The ratio of non-synonymous to synonymous substitutions (dN/dS) is a useful
      measure of the strength and mode of natural selection acting on protein-coding
      genes. It is widely used to study patterns of selection on protein genes on a
      genomic scale-from the small genomes of viruses, bacteria, and parasitic
      eukaryotes to the largest eukaryotic genomes. In this chapter we describe all the
      steps necessary to calculate the dN/dS of all the genes using at least two
      genomes. We include a brief discussion on assigning orthologs, and of codon-aware
      alignment of orthologs. We then describe how to use the CODEML program of the
      PAML package for phylogenetic analysis to calculate the dN/dS and how to perform
      some statistical tests for positive selection. We then outline some methods for
      interpreting output and describe how one may use this data to make discoveries
      about the biology of your species. Finally, as a worked example we show all the
      steps we used to calculate dN/dS for 3,261 orthologs from six Plasmodium species,
      including tests for adaptive evolution (see worked_example.pdf).

PMID- 25388109
TI  - Exploiting genetic variation to discover genes involved in important disease
      phenotypes.
AB  - Elucidating the underlying genetic determinants of disease pathology is still in
      the early stages for many pathogenic parasites. There have, however, been a
      number of advances in which natural genetic diversity has been successfully
      utilized to untangle the often complex interactions between parasite and host. In
      this chapter we discuss various methods capable of exploiting this natural
      genetic variation to determine genes involved in phenotypes of interest, using
      virulence in the pathogenic parasite Trypanosoma brucei as a case study. This
      species is an ideal system to benefit from such an approach as there are several
      well-characterized laboratory strains; the parasite undergoes genetic exchange in
      both the field and the laboratory, and is amenable to efficient reverse genetics
      and RNAi. 

PMID- 25388110
TI  - Identification and analysis of ingi-related retroposons in the trypanosomatid
      genomes.
AB  - Transposable elements (TE), defined as discrete pieces of DNA that can move from
      one site to another site in genomes, represent significant components of
      eukaryotic genomes, including trypanosomatids. Up to 5% of the trypanosomatid
      genome content is composed of retroposons of the ingi clade, further divided into
      subclades and subfamilies ranging from short extinct truncated elements (SIDER)
      to long active elements (ingi). Important differences in ingi-related retroposon
      content have been reported between trypanosomatid species. For instance,
      Leishmania spp. have expanded and recycled a whole SIDER family to fulfill an
      important biological pathway, i.e., regulation of gene expression, while
      trypanosome genomes are primarily composed of active elements. Here, we present
      an overview of the computational methods used to identify, annotate, and analyze
      ingi-related retroposons for providing a comprehensive picture of all these TE
      families in newly available trypanosomatid genome sequences.

PMID- 25388111
TI  - Approaches for studying mRNA decay mediated by SIDER2 retroposons in Leishmania.
AB  - Regulated mRNA turnover is a highly important process in the control of gene
      expression in Leishmania and related trypanosomatid protozoa, as these organisms
      lack control at the level of transcription initiation. A large number of
      Leishmania transcripts harbor in their 3'UTRs two phylogenetically distinct
      subfamilies of extinct Short Interspersed DEgenerate Retroposons (SIDER1 and
      SIDER2) that are involved in posttranscriptional regulation of gene expression.
      We have shown recently that members of the SIDER2 subfamily promote mRNA
      destabilization and that degradation of SIDER2-containing mRNAs is initiated by
      site-specific endonucleolytic cleavage within the second 79-nt SIDER2 signature
      sequence without prior shortening of the poly(A) tail. Here, we describe
      experimental procedures for studying the mechanism of SIDER2-mediated mRNA decay.
      These include RNase protection assays to identify in vivo-generated mRNA decay
      intermediates following endonucleolytic cleavage, primer extension analysis to
      precisely map the site(s) of cleavage within SIDER2, and deadenylation assays to
      assess the polyadenylation state of unstable SIDER2-containing mRNAs in
      Leishmania. 

PMID- 25388112
TI  - Gene suppression in schistosomes using RNAi.
AB  - Schistosomiasis is a neglected tropical disease responsible for the death of more
      than 300,000 people every year. The disease is caused by intravascular parasitic
      platyhelminths called schistosomes. Treatment and control of schistosomiasis rely
      on a single drug, praziquantel, and concern exists over the possible emergence of
      resistance to this drug. The recent completion of the genome sequences of the
      three main worm species that cause schistosomiasis in humans has raised hope for
      the development of new interventions to treat the disease. RNA interference
      (RNAi), a mechanism by which gene-specific double-stranded RNA (dsRNA) triggers
      degradation of homologous mRNA transcripts, has emerged as an important tool to
      evaluate and validate new potential drug targets. In addition, RNAi has been used
      to explore the basic biology of these debilitating parasites. RNAi can be
      achieved in all stages of the parasite's life cycle in which it has been tested.
      In this review, we describe methods for applying RNAi to suppress gene expression
      in the intra-mammalian life stages (adults and schistosomula) of Schistosoma
      mansoni. We describe procedures for isolating and culturing the parasites,
      preparing and delivering dsRNA targeting a specific gene, as well as a procedure
      to evaluate gene suppression by quantitative real-time PCR. 

PMID- 25388113
TI  - Construction of Trypanosoma brucei Illumina RNA-Seq libraries enriched for
      transcript ends.
AB  - High-throughput RNA sequencing (RNA-Seq) has quickly occupied center stage in the
      repertoire of available tools for transcriptomics. Among many advantages, the
      single-nucleotide resolution of this powerful approach allows mapping on a genome
      wide scale of splice junctions and polyadenylation sites, and thus, the precise
      definition of mature transcript boundaries. This greatly facilitated the
      transcriptome annotation of the human pathogen Trypanosoma brucei, a protozoan
      organism in which all mRNA molecules are matured by spliced leader (SL) trans
      splicing from longer polycistronic precursors. The protocols described here for
      the generation of three types of libraries for Illumina RNA-Seq, 5'-SL enriched,
      5'-triphosphate-end enriched, and 3'-poly(A) enriched, enabled the discovery of
      an unprecedented heterogeneity of pre-mRNA-processing sites, a large number of
      novel coding and noncoding transcripts from previously unannotated genes, and
      quantify the cellular abundance of RNA molecules. The method for producing 5'
      triphosphate-end-enriched libraries was instrumental for obtaining evidence that
      transcription initiation by RNA polymerase II in trypanosomes is bidirectional
      and biosynthesis of mRNA precursors is primed not only at the beginning of
      unidirectional gene clusters, but also at specific internal sites. 

PMID- 25388114
TI  - Techniques to study epigenetic control and the epigenome in parasites.
AB  - Epigenetics is the study of heritable changes in gene expression that occur
      independent of the DNA sequence. Due to their intimacy with DNA, histones have a
      central role in chromatin structure and epigenetic regulation. Their tails are
      subject to posttranslational modifications (PTMs) that together with chromatin
      remodeling proteins control the access of different proteins to DNA and allow a
      precise response to different environmental conditions. The first part of this
      chapter is dedicated to histone enrichment methods that allow the study of
      histones using techniques such as immunoblot or mass spectrometry for the mapping
      of the histone PTM network. Next we describe chromatin immunoprecipitation-based
      techniques (ChIP) for study of the epigenome. ChIP followed by microarray or next
      generation sequencing enables the precise genomic localization of protein-DNA
      interactions. These techniques for genome-wide profiling of chromatin provide
      powerful and efficient tools to study the epigenome. 

PMID- 25388115
TI  - The genome-wide identification of promoter regions in Toxoplasma gondii.
AB  - Parasites change their transcriptional systems in different developmental stages
      and in response to environmental changes. To investigate the molecular mechanisms
      that underlie transcriptional regulation, it is essential to identify the exact
      positions of the transcriptional start sites (TSSs) and characterize the upstream
      promoter regions. However, it has been essentially impossible to obtain
      comprehensive information using conventional methods. Here, we introduce our TSS
      seq method, which combines full-length technology, oligo-capping, and rapidly
      developing next-generation sequencing technology. TSS-seq has enabled
      identification of TSS positions and upstream promoter activities as digital TSS
      tag counts within a reasonable cost and time frame. In this chapter, we describe
      in detail the TSS-seq method for the identification and characterization of the
      promoters in Toxoplasma gondii. 

PMID- 25388116
TI  - RNA-seq approaches for determining mRNA abundance in Leishmania.
AB  - High-throughput sequencing of cDNA copies of mRNA (RNA-seq) provides a digital
      read-out of mRNA levels over several orders of magnitude, as well as mapping the
      transcripts to the nucleotide level. Here we describe an RNA-seq approach that
      exploits the 39-nucleotide mini-exon or spliced leader (SL) sequence found at the
      5' end of all Leishmania (and other trypanosomatid) mRNAs. 

PMID- 25388117
TI  - Protein microarrays for parasite antigen discovery.
AB  - The host serological profile to a parasitic infection, such as schistosomiasis,
      can be used to define potential vaccine and diagnostic targets. Determining the
      host antibody response using traditional approaches is hindered by the large
      number of putative antigens in any parasite proteome. Parasite protein
      microarrays offer the potential for a high-throughput host antibody screen to
      simplify this task. In order to construct the array, parasite proteins are
      selected from available genomic sequence and protein databases using
      bioinformatic tools. Selected open reading frames are PCR amplified, incorporated
      into a vector for cell-free protein expression, and printed robotically onto
      glass slides. The protein microarrays can be probed with antisera from
      infected/immune animals or humans and the antibody reactivity measured with
      fluorophore labeled antibodies on a confocal laser microarray scanner to identify
      potential targets for diagnosis or therapeutic or prophylactic intervention. 

PMID- 25388118
TI  - A transposon-based tool for transformation and mutagenesis in trypanosomatid
      protozoa.
AB  - The ability of transposable elements to mobilize across genomes and affect the
      expression of genes makes them exceptional tools for genetic manipulation
      methodologies. Several transposon-based systems have been modified and
      incorporated into shuttle mutagenesis approaches in a variety of organisms. We
      have found that the Mos1 element, a DNA transposon from Drosophila mauritiana, is
      suitable and readily adaptable to a variety of strategies to the study of
      trypanosomatid parasitic protozoa. Trypanosomatids are the causative agents of a
      wide range of neglected diseases in underdeveloped regions of the globe. In this
      chapter we describe the basic elements and the available protocols for the in
      vitro use of Mos1 derivatives in the protozoan parasite Leishmania. 

PMID- 25388119
TI  - Separation of basic proteins from Leishmania using a combination of Free flow
      electrophoresis (FFE) and 2D electrophoresis (2-DE) under basic conditions.
AB  - Basic proteins, an important class of proteins in intracellular organisms such as
      Leishmania, are usually underrepresented on 2D gels. This chapter describes a
      method combining basic proteins fractionation using Free flow electrophoresis in
      isoelectric focusing mode (IEF-FFE) followed by protein separation using two
      dimensional gel electrophoresis (2-DE) in basic conditions. The combination of
      these two techniques represents a great improvement for the visualization of
      Leishmania proteins with basic pI using 2D gels. 

PMID- 25388120
TI  - Proteomic analysis of posttranslational modifications using iTRAQ in Leishmania.
AB  - iTRAQ is a high coverage quantitative proteomics technique identifies and
      quantitates abundance changes of multiple (up to eight) distinct protein samples.
      To date, one iTRAQ-MS/MS assay can identify up to quarter of cells proteome. Each
      of the eight tags covalently binds to the N-terminus as well as arginine and
      lysine side chains of peptides, enabling labeling of the entire peptide
      population in each sample. Following tagging, the various protein samples are
      mixed and subjected to LC-MS/MS analysis. In the first round identical peptides
      from the different protein populations focus in a single pick. Subsequently,
      sequence of each peptide is determined. The tags whose m/z is similar to that of
      natural amino acids are used to determine relative abundance. To date, iTRAQ
      enabled identification of almost 2,000 Leishmania proteins. Here, we provide
      protocols for protein abundance changes and for phosphoproteomics analysis in
      Leishmania parasites. 

PMID- 25388121
TI  - Large-scale differential proteome analysis in Plasmodium falciparum under drug
      treatment.
AB  - Here, we establish a methodology for large-scale quantitative proteomics using
      SIL (stable isotope labeling) to examine protein expression changes in
      trophozoite stages of the malaria parasite Plasmodium falciparum following drug
      treatment. For this purpose, exposure to (13)C6 (15)N1-isoleucine was optimized
      in order to obtain 99% atomic enrichment. Proteome fractionation with anion
      exchange chromatography was used to reduce sample complexity and increase
      quantitative coverage of protein expression. Tryptic peptides of subfractions
      were subjected to SCX/RP separation, measured by LC-MS/MS, and quantified using
      the software tool Census. In drug-treated parasites, we identified a total number
      of 1,253 proteins, thus increasing the overall number of proteins so far
      identified in the trophozoite stage by 30% in the previous literature. A relative
      quantification was obtained for more than 800 proteins. About 5% of proteins
      showed a clear up- or downregulation upon drug treatment.

PMID- 25388122
TI  - Use of (13)C stable isotope labelling for pathway and metabolic flux analysis in
      Leishmania parasites.
AB  - This protocol describes the combined use of metabolite profiling and stable
      isotope labelling to define pathways of central carbon metabolism in the protozoa
      parasite, Leishmania mexicana. Parasite stages are cultivated in standard or
      completely defined media and then rapidly transferred to chemically equivalent
      media containing a single (13)C-labelled nutrient. The incorporation of label can
      be followed over time or after establishment of isotopic equilibrium by
      harvesting parasites with rapid metabolic quenching. (13)C enrichment of multiple
      intracellular polar and apolar (lipidic) metabolites can be quantified using gas
      chromatography-mass spectrometry (GC-MS), while the uptake and secretion of (13)C
      labelled metabolites can be measured by (13)C-NMR. Analysis of the mass
      isotopomer distribution of key metabolites provides information on pathway
      structure, while analysis of labelling kinetics can be used to infer metabolic
      fluxes. This protocol is exemplified using L. mexicana labelled with (13)C-U
      glucose. The method can be used to measure perturbations in parasite metabolism
      induced by drug inhibition or genetic manipulation of enzyme levels and is
      broadly applicable to any cultured parasite stages. 

PMID- 25388123
TI  - Molecular genotyping of Trypanosoma cruzi for lineage assignment and population
      genetics.
AB  - Trypanosoma cruzi, the etiological agent of Chagas disease, remains a major
      public health problem in Latin America. Infection with T. cruzi is lifelong and
      can lead to a spectrum of pathological sequelae ranging from subclinical to
      lethal cardiac and/or gastrointestinal complications. Isolates of T. cruzi can be
      assigned to six genetic lineages or discrete typing units (DTUs), which are
      broadly associated with disparate ecologies, transmission cycles, and
      geographical distributions. This extensive genetic diversity is also believed to
      contribute to the clinical variation observed among chagasic patients.
      Unravelling the population structure of T. cruzi is fundamental to understanding
      Chagas disease epidemiology, developing control strategies, and resolving the
      relationship between parasite genotype and clinical prognosis. To date, no
      single, widely validated, genetic target allows unequivocal resolution to DTU
      level. In this chapter we present standardized methods for strain DTU assignment
      using PCR-restriction fragment length polymorphism analysis (PCR-RFLP) and
      nuclear multilocus sequence typing (MLST). PCR-RFLPs have the advantages of
      simplicity and reproducibility, requiring limited expertise and few laboratory
      consumables. MLST data are more laborious to generate but more informative; DNA
      sequences are readily transferable between research groups and amenable to
      recombination detection and intra-lineage analyses. We also recommend a
      mitochondrial (maxicircle) MLST scheme and a panel of 28 microsatellite loci for
      higher resolution population genetics studies. Due to the scarcity of T. cruzi in
      blood and tissue, all of these genotyping techniques have limited sensitivity
      when applied directly to clinical or biological specimens, particularly when
      targets are single (MLST) or low copy number (PCR-RFLPs). We therefore describe
      essential protocols to isolate parasites, derive biological clones, and extract
      T. cruzi genomic DNA from field and clinical samples.

PMID- 25388124
TI  - Screening Leishmania donovani complex-specific genes required for visceral
      disease.
AB  - Leishmania protozoan parasites are the causing agent of leishmaniasis. Depending
      on the infecting species, Leishmania infection can causes a wide variety of
      diseases such as self-healing cutaneous lesions by L. major and fatal visceral
      leishmaniasis by L. donovani and L. infantum. Comparison of the visceral disease
      causing L. infantum genome with cutaneous disease causing L. major and L.
      braziliensis genomes has identified 25 L. infantum (L. donovani complex) species
      specific genes that are absent or pseudogenes in L. major and L. braziliensis. To
      investigate whether these L. donovani complex species-specific genes are involved
      in visceral infection, we cloned these genes from L. donovani and introduced them
      into L. major and then determined whether the transgenic L. major had an
      increased ability to survive in liver and spleen of BALB/c mice. Several of these
      L. donovani complex specific genes were found to significantly increase L. major
      survival in visceral organs in BALB/c mice including the A2 and Ld2834 genes,
      while down regulation of these genes in L. donovani by either antisense RNA or
      gene knockout dramatically reduced L. donovani virulence in BALB/c mice. This
      demonstrated that L. donovani complex species-specific genes play important roles
      in visceral infection. In this chapter, we describe procedures to screen L.
      donovani complex specific genes required for visceral infection by cross species
      transgenic expression, gene deletion targeting and measuring infection levels in
      mice. 

PMID- 25388125
TI  - Using the jackknife for estimation in log link Bernoulli regression models.
AB  - Bernoulli (or binomial) regression using a generalized linear model with a log
      link function, where the exponentiated regression parameters have interpretation
      as relative risks, is often more appropriate than logistic regression for
      prospective studies with common outcomes. In particular, many researchers regard
      relative risks to be more intuitively interpretable than odds ratios. However,
      for the log link, when the outcome is very prevalent, the likelihood may not have
      a unique maximum. To circumvent this problem, a 'COPY method' has been proposed,
      which is equivalent to creating for each subject an additional observation with
      the same covariates except the response variable has the outcome values
      interchanged (1's changed to 0's and 0's changed to 1's). The original response
      is given weight close to 1, while the new observation is given a positive weight
      close to 0; this approach always leads to convergence of the maximum likelihood
      algorithm, except for problems with convergence due to multicollinearity among
      covariates. Even though this method produces a unique maximum, when the outcome
      is very prevalent, and/or the sample size is relatively small, the COPY method
      can yield biased estimates. Here, we propose using the jackknife as a bias
      reduction approach for the COPY method. The proposed method is motivated by a
      study of patients undergoing colorectal cancer surgery.

PMID- 25388126
TI  - Microsporidial polymyositis in human immunodeficiency virus-infected patients, a
      rare life-threatening opportunistic infection: clinical suspicion, diagnosis, and
      management in resource-limited settings.
AB  - INTRODUCTION: Microsporidial myositis is a rare opportunistic infection that has
      been reported in HIV-infected and HIV-uninfected immunocompromised patients.
      METHODS: In this study we present a retrospective analysis of 5 cases of
      microsporidial myositis in HIV-infected patients, including the clinical,
      laboratory, and histologic features, and a review of the literature. RESULTS:
      Five young men with HIV infection [median CD4 count of 20 cells (range 14
      144)/mm(3) ] who presented with signs and symptoms suggestive of myositis
      underwent EMG-NCV and muscle biopsy, which revealed signs compatible with
      microsporidial myositis. Early and aggressive treatment led to improvement in 3
      patients. Two of the 5 patients died due to a delay in diagnosis, because the
      spores were mistaken for Candida without confirmatory stains or a high index of
      suspicion. CONCLUSIONS: Myositis in HIV-infected patients with low CD4 counts
      should be evaluated using muscle biopsy. A high index of suspicion is required
      for early diagnosis of microsporidial myositis in HIV-infected patients. Early
      diagnosis and immediate, aggressive treatment are the keys to favorable outcomes
      in these patients.

PMID- 25388127
TI  - Facilitation and interference during the preparation of bimanual movements:
      contributions from starting locations, movement amplitudes, and target locations.
AB  - Symmetric, target-directed, bimanual movements take less time to prepare than
      asymmetric movements (Diedrichsen et al. in Cerebral Cortex 16(12):1729-1738,
      2006; Heuer and Klein in Psychol Res 70(4):229-244, 2006b). The preparation
      savings for symmetric movements may be related to the specification of symmetric
      amplitudes, target locations, or both. The goals of this study were to determine
      which symmetric movement parameters facilitate the preparation of bimanual
      movements and to compare the size of the facilitation for different parameters.
      Thirty participants performed bimanual reaching movements that varied in terms of
      the symmetry/asymmetry of starting locations, movement amplitudes, and target
      locations. Reaction time savings were examined by comparing movements that had
      one symmetric parameter (and two asymmetric parameters) to movements with all
      asymmetric parameters. We observed significant savings (~10 ms) for movements
      with symmetric amplitudes and movements with symmetric target locations. Reaction
      time costs were examined by comparing movements that had two asymmetric
      parameters (and one symmetric parameter) to movements with all symmetric
      parameters. We observed significant reaction time costs (~13 ms) for all
      movements with asymmetric amplitudes. These results suggest that movement
      preparation is facilitated when amplitudes or target locations are symmetric and
      that movement preparation suffers interference when amplitudes are asymmetric.
      The relative importance of the three parameters to movement preparation, from
      most to least important, is movement amplitudes, target locations, and then
      starting locations. Interference with asymmetric amplitudes or target locations
      may be caused by cross-talk between concurrent processes of parameter
      specification during response programming.

PMID- 25388128
TI  - A gender-dependent analysis of Cushing's disease in childhood: pre- and
      postoperative follow-up.
AB  - OBJECTIVE: To analyse gender differences in the clinical presentation and
      recovery of paediatric patients with Cushing's disease (CD) after transsphenoidal
      surgery (TSS). Indeed, gender differences between paediatric patients with CD
      during presentation, after TSS and postoperative recovery have not been
      adequately studied. DESIGN: Data were obtained and retrospectively analysed from
      clinical reports and biochemical tests at the time of presentation, 5-9 days
      after TSS and at the 6 and 12 months postoperative follow-up visits to determine
      hypothalamic-pituitary-adrenal axis (HPAA) recovery. PATIENTS: Data from 102
      paediatric patients (48 females, 54 males, mean age 12.9 +/- 3.0) with CD who
      underwent TSS at the National Institute of Health (NIH) Clinical Center between
      1997 and 2011. RESULTS: There was equal distribution of paediatric CD between
      males and females (53% vs 47%; n = 102, P = 0.484). Males were more likely than
      females to present with higher mean BMI Z-scores (2.2 +/- 0.7 vs 1.9 +/- 0.6, P =
      0.0079), lower mean height Z-scores (-1.2 +/- 1.3 vs -0.7 +/- 1.1, P = 0.0467)
      and higher median plasma ACTH (12.2 vs 8.5 pmol/l; P = 0.0495). Females did not
      present more frequently with any single sign or symptom. No significant
      differences were found between males and females for CD cure rates 5-9 days after
      TSS (87.0% males vs 87.5% females, P = 1.0), long-term cure rates (86.5% vs
      93.7%; n = 69; P = 0.4374) and HPAA recovery time (11.2 +/- 2.5 vs 11.7 +/- 2.5
      months; n = 47; P = 0.1992). CONCLUSIONS: Paediatric CD is found to have equal
      distribution between males and females, but male patients present with elevated
      BMI and potentially shorter height and higher plasma ACTH. There is no
      significant difference in the cure rate or HPAA recovery time after TSS between
      males and females.

PMID- 25388129
TI  - History of leptospirosis and leptospira.
AB  - Leptospira was isolated and identified as the causative agent of the severe human
      syndrome Weil's disease about 100 years ago almost simultaneously, but
      independently, by workers in Japan and Europe. Since that time leptospires have
      been isolated from almost all mammalian species on every continent except
      Antarctica, with leptospirosis now recognized as the most widespread zoonosis
      worldwide and also a major cause of disease in many domestic animal species.
      Recent advances in molecular taxonomy have facilitated the development of a
      rational classification system, while the availability of genome sequences and
      the development of mutagenesis systems have begun to shed light on mechanisms of
      pathogenesis that appear to be unique to Leptospira.

PMID- 25388130
TI  - Systematics of leptospiraceae.
AB  - Leptospires are spirochetes that may be free-living saprophytes found in
      freshwater or may cause acute or chronic infection of animals. The family
      Leptospiraceae comprises three genera: Leptospira Leptospira Leptonema Leptonema,
      and Turneriella Turneriella. Within the genus Leptospira, three clades can be
      distinguished, of pathogens, nonpathogens, and an intermediate group. Leptospires
      are further divided into serovars; antigenically related serovars are clustered
      into serogroups for convenience.

PMID- 25388131
TI  - Leptospiral structure, physiology, and metabolism.
AB  - Members of the family Leptospiraceae are thin, spiral, highly motile bacteria
      that are best visualized by darkfield microscopy. These characteristics are
      shared with other members of the Order Spirochaetales, but few additional
      parallels exist among spirochetes. This chapter describes basal features of
      Leptospira Leptospira that are central to survival and, in the case of pathogenic
      leptospiral species, intimately linked with pathogenesis, including its
      morphology, characteristic motility, and unusual metabolism. This chapter also
      describes the general methodology and critical requirements for in vitro
      cultivation and storage of Leptospira within a laboratory setting.

PMID- 25388132
TI  - Genomics, proteomics, and genetics of leptospira.
AB  - Recent advances in molecular genetics, such as the ability to construct defined
      mutants, have allowed the study of virulence factors and more generally the
      biology in Leptospira. However, pathogenic leptospires remain much less easily
      transformable than the saprophyte L. biflexa and further development and
      improvement of genetic tools are required. Here, we review tools that have been
      used to genetically manipulate Leptospira. We also describe the major advances
      achieved in both genomics and postgenomics technologies, including
      transcriptomics and proteomics. 

PMID- 25388134
TI  - Animal leptospirosis.
AB  - Leptospirosis is a global disease of animals, which can have a major economic
      impact on livestock industries and is an important zoonosis. The current
      knowledge base is heavily biased towards the developed agricultural economies.
      The disease situation in the developing economies presents a major challenge as
      humans and animals frequently live in close association. The severity of disease
      varies with the infecting serovar and the affected species, but there are many
      common aspects across the species; for example, the acute phase of infection is
      mostly sub-clinical and the greatest economic losses arise from chronic infection
      causing reproductive wastage. The principles of, and tests for, diagnosis,
      treatment, control and surveillance are applicable across the species.

PMID- 25388135
TI  - The molecular basis of leptospiral pathogenesis.
AB  - The mechanisms of disease pathogenesis in leptospirosis are poorly defined.
      Recent developments in the application of genetic tools in the study of
      Leptospira have advanced our understanding by allowing the assessment of mutants
      in animal models. As a result, a small number of essential virulence factors have
      been identified, though most do not have a clearly defined function. Significant
      advances have also been made in the in vitro characterization of leptospiral
      interaction with host structures, including extracellular matrix proteins (such
      as laminin, elastin, fibronectin, collagens), proteins related to hemostasis
      (fibrinogen, plasmin), and soluble mediators of complement resistance (factor H,
      C4b-binding protein), although none of these in vitro findings has been
      translated to the host animal. Binding to host structures may permit colonization
      of the host, prevention of blood clotting may contribute to hemorrhage, while
      interaction with complement resistance mediators may contribute to survival in
      serum. While not a classical intracellular pathogen, the interaction of
      leptospires and phagocytic cells appears complex, with bacteria surviving uptake
      and promoting apoptosis; mutants relating to these processes (such as cell
      invasion and oxidative stress resistance) are attenuated in vivo. Another feature
      of leptospiral biology is the high degree of functional redundancy and the
      surprising lack of attenuation of mutants in what appear to be certain virulence
      factors, such as LipL32 and LigB. While many advances have been made, there
      remains a lack of understanding of how Leptospira causes tissue pathology. It is
      likely that leptospires have many novel pathogenesis mechanisms that are yet to
      be identified. 

PMID- 25388133
TI  - Leptospirosis in humans.
AB  - Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in
      many tropical regions and causes large epidemics after heavy rainfall and
      flooding. Infection results from direct or indirect exposure to infected
      reservoir host animals that carry the pathogen in their renal tubules and shed
      pathogenic leptospires in their urine. Although many wild and domestic animals
      can serve as reservoir hosts, the brown rat (Rattus norvegicus) is the most
      important source of human infections. Individuals living in urban slum
      environments characterized by inadequate sanitation and poor housing are at high
      risk of rat exposure and leptospirosis. The global burden of leptospirosis is
      expected to rise with demographic shifts that favor increases in the number of
      urban poor in tropical regions subject to worsening storms and urban flooding due
      to climate change. Data emerging from prospective surveillance studies suggest
      that most human leptospiral infections in endemic areas are mild or asymptomatic.
      Development of more severe outcomes likely depends on three factors:
      epidemiological conditions, host susceptibility, and pathogen virulence (Fig. 1).
      Mortality increases with age, particularly in patients older than 60 years of
      age. High levels of bacteremia are associated with poor clinical outcomes and,
      based on animal model and in vitro studies, are related in part to poor
      recognition of leptospiral LPS by human TLR4. Patients with severe leptospirosis
      experience a cytokine storm characterized by high levels of IL-6, TNF-alpha, and
      IL-10. Patients with the HLA DQ6 allele are at higher risk of disease, suggesting
      a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis
      typically presents as a nonspecific, acute febrile illness characterized by
      fever, myalgia, and headache and may be confused with other entities such as
      influenza and dengue fever. Newer diagnostic methods facilitate early diagnosis
      and antibiotic treatment. Patients progressing to multisystem organ failure have
      widespread hematogenous dissemination of pathogens. Nonoliguric (high output)
      renal dysfunction should be supported with fluids and electrolytes. When oliguric
      renal failure occurs, prompt initiation of dialysis can be life saving. Elevated
      bilirubin levels are due to hepatocellular damage and disruption of intercellular
      junctions between hepatocytes, resulting in leaking of bilirubin out of bile
      caniliculi. Hemorrhagic complications are common and are associated with
      coagulation abnormalities. Severe pulmonary hemorrhage syndrome due to extensive
      alveolar hemorrhage has a fatality rate of >50 %. Readers are referred to
      earlier, excellent summaries related to this subject (Adler and de la Pena
      Moctezuma 2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009;
      Levett 2001; McBride et al. 2005).

PMID- 25388137
TI  - Host response to leptospira infection.
AB  - Pathogenic Leptospira has the capacity to infect a broad range of mammalian
      hosts. Leptospirosis may appear as an acute, potentially fatal infection in
      accidental hosts, or progress into a chronic, largely asymptomatic infection in
      natural maintenance hosts. The course that Leptospira infection follows is
      dependent upon poorly understood factors, but is heavily influenced by both the
      host species and bacterial serovar involved in infection. Recognition of pathogen
      associated molecular patterns (PAMPs) by a variety of host pattern recognition
      receptors (PRRs) activates the host immune system. The outcome of this response
      may result in bacterial clearance, limited bacterial colonization of a few target
      organs, principally the kidney, or induction of sepsis as the host succumbs to
      infection and dies. This chapter describes current knowledge of how the host
      recognizes Leptospira and responds to infection using innate and acquired immune
      responses. Aspects of immune-mediated pathology and pathogen strategies to evade
      the host immune response are also addressed. 

PMID- 25388138
TI  - Vaccines against leptospirosis.
AB  - Vaccines against leptospirosis followed within a year of the first isolation of
      Leptospira, with the first use of a killed whole cell bacterin vaccine in guinea
      pigs published in 1916. Since then, bacterin vaccines have been used in humans,
      cattle, swine, and dogs and remain the only vaccines licensed at the present
      time. The immunity elicited is restricted to serovars with related
      lipopolysaccharide (LPS) antigen. Likewise, vaccines based on LPS antigens have
      clearly demonstrated protection in animal models, which is also at best serogroup
      specific. The advent of leptospiral genome sequences has allowed a reverse
      vaccinology approach for vaccine development. However, the use of inadequate
      challenge doses and inappropriate statistical analysis invalidates many of the
      claims of protection with recombinant proteins. 

PMID- 25388136
TI  - The leptospiral outer membrane.
AB  - The outer membrane (OM) is the front line of leptospiral interactions with their
      environment and the mammalian host. Unlike most invasive spirochetes, pathogenic
      leptospires must be able to survive in both free-living and host-adapted states.
      As organisms move from one set of environmental conditions to another, the OM
      must cope with a series of conflicting challenges. For example, the OM must be
      porous enough to allow nutrient uptake, yet robust enough to defend the cell
      against noxious substances. In the host, the OM presents a surface decorated with
      adhesins and receptors for attaching to, and acquiring, desirable host molecules
      such as the complement regulator, Factor H.Factor H. On the other hand, the OM
      must enable leptospires to evade detection by the host's immune system on their
      way from sites of invasion through the bloodstream to the protected niche of the
      proximal tubule. The picture that is emerging of the leptospiral OM is that,
      while it shares many of the characteristics of the OMs of spirochetes and Gram
      negative bacteria, it is also unique and different in ways that make it of
      general interest to microbiologists. For example, unlike most other pathogenic
      spirochetes, the leptospiral OM is rich in lipopolysaccharide (LPS). Leptospiral
      LPS is similar to that of Gram-negative bacteria but has a number of unique
      structural features that may explain why it is not recognized by the LPS-specific
      Toll-like receptor 4 of humans. As in other spirochetes, lipoproteins are major
      components of the leptospiral OM, though their roles are poorly understood. The
      functions of transmembrane outer membrane proteins (OMPs) in many cases are
      better understood, thanks to homologies with their Gram-negative counterparts and
      the emergence of improved genetic techniques. This chapter will review recent
      discoveries involving the leptospiral OM and its role in leptospiral physiology
      and pathogenesis.

PMID- 25388139
TI  - The role of leptospirosis reference laboratories.
AB  - The general goal of reference centres is to support the community, from
      diagnostic laboratories to research institutions, in the execution of their work
      by providing reference strains and reagents and giving instructions and
      recommendations to individual colleagues and national and international
      organisations on a wide variety of issues. There are different levels of
      reference centres, from local to international, with an increasing package of
      tasks and responsibilities. Local reference centres might limit activities to
      diagnostic confirmation by applying standard testing, while international
      reference centres cover a wider range of activities from design, validation and
      harmonisation of diagnostic and reference technologies to international
      monitoring associated with recommendations on the global burden and distribution
      of leptospirosis and its prevention and control to national and international
      health decision makers. This chapter focusses on four major pillars constituting
      reference tasks in addition to the obvious provision of reference substances,
      i.e. Research and training, Diagnosis, Identification of Leptospira and
      Surveillance. Due to financial and organisational constraints, reference centres
      are restricted in their capacity for basic research and consequently focus on
      applied research into various aspects of leptospirosis. They offer training,
      either individually or groupwise, that might vary from standard technologies to
      novel sophisticated methodologies, depending on the need and requests of the
      trainee. Most reference centres are involved in the confirmation of preliminary
      diagnosis obtained at peripheral levels, such as local hospitals and health
      centres, while other major activities involve the design and validation of
      diagnostics, their international harmonisation and quality assurance.
      Identification of causative Leptospira strains (or serovars) is key to the
      identification of infection sources and is critical for surveillance. Hence,
      reference centres also focus on the development, application and provision of
      methods that are required for unambiguous characterisation of new and recognised
      Leptospira strains and the maintenance of the integrity of strain collections. In
      line with their central role, reference centres are frequently associated with
      local, national and/or international surveillance activities linked to an
      advisory role and the production of guidelines. Such surveillance activities
      usually comprise collation of morbidity and mortality data, signalling of
      outbreaks and the investigation of infection sources and risks.

PMID- 25388140
TI  - Modification of atmospheric sand-associated bacterial communities during Asian
      sandstorms in China and South Korea.
AB  - The transport of desert soil into the atmosphere during desert sandstorms can
      affect the Earth's climate and environmental health. Asian desert sandstorms
      occur almost every year during the Spring, as the atmosphere in the Northern
      hemisphere warms. It is conceivable that these Asian desert sandstorms may
      transport microbes from deserts, such as the Gobi and Taklamaken deserts, over
      long distances in China, east Asia and the Pacific. In this study, we examined
      local atmospheric sand particle-associated bacterial populations collected in the
      absence (sterile sand exposed for 24 h to the air in the absence of a sandstorm)
      and presence of sandstorms in five Asian cities. We used pyrosequencing of PCR
      amplified 16S rDNA genes from sand-extracted total DNA to overcome cultivation
      limitations of bacterial enumeration. We found that >90% of the control and
      sandstorm sequences could be classified as representing bacteria belonging to
      four phyla: Proteobacteria, Bacteriodetes, Actinobacteria and Firmicutes. The
      sand-associated bacterial populations in sandstorm samples were distinct from
      sand-associated bacteria in the absence of a sandstorm. Members of the phylum
      Proteobacteria were found to significantly increase in sandstorm samples
      (P=0.01). Principal component analyses showed that the sand-associated bacterial
      populations were best clustered by sampling year, rather than location. DNA
      sequences representing bacteria belonging to several genera (including putative
      human pathogens) were observed to increase in sand-associated samples from
      sandstorms, whereas others were found to decrease, when comparing sand-associated
      bacterial populations versus those in control samples, suggesting
      human/environmental implications of sandstorm events. 

PMID- 25388141
TI  - A parameter to quantify the degree of genetic mixing among individuals in hybrid
      populations.
AB  - Hybridization between genetically distinct taxa is a complex evolutionary
      process. One challenge to studying hybrid populations is quantifying the degree
      to which non-native genes have become evenly mixed among individuals in the
      population. In this paper, we present a variance-based parameter, md, that
      measures the degree to which non-native genes are evenly distributed among
      individuals in a population. The parameter has a minimum value of 0 for
      populations in which individuals from multiple taxa are present but have not
      interbred, and a maximum value of 1 for populations in which all individuals have
      the same amount of non-native ancestry. A recurrence equation showed that
      relatively few generations of random mating are required for md to approach 1
      (indicating a well-mixed population), and that md is independent of initial
      amounts of non-native ancestry. The parameter is mathematically equivalent to FST
      and we show how existing formulae for FST can be used to estimate md when
      diagnostic loci are available. Computer simulations showed this estimator to have
      very little bias for realistic amounts of data. 

PMID- 25388142
TI  - Potential and limits to unravel the genetic architecture and predict the
      variation of Fusarium head blight resistance in European winter wheat (Triticum
      aestivum L.).
AB  - Genome-wide mapping approaches in diverse populations are powerful tools to
      unravel the genetic architecture of complex traits. The main goals of our study
      were to investigate the potential and limits to unravel the genetic architecture
      and to identify the factors determining the accuracy of prediction of the
      genotypic variation of Fusarium head blight (FHB) resistance in wheat (Triticum
      aestivum L.) based on data collected with a diverse panel of 372 European
      varieties. The wheat lines were phenotyped in multi-location field trials for FHB
      resistance and genotyped with 782 simple sequence repeat (SSR) markers, and 9k
      and 90k single-nucleotide polymorphism (SNP) arrays. We applied genome-wide
      association mapping in combination with fivefold cross-validations and observed
      surprisingly high accuracies of prediction for marker-assisted selection based on
      the detected quantitative trait loci (QTLs). Using a random sample of markers not
      selected for marker-trait associations revealed only a slight decrease in
      prediction accuracy compared with marker-based selection exploiting the QTL
      information. The same picture was confirmed in a simulation study, suggesting
      that relatedness is a main driver of the accuracy of prediction in marker
      assisted selection of FHB resistance. When the accuracy of prediction of three
      genomic selection models was contrasted for the three marker data sets, no
      significant differences in accuracies among marker platforms and genomic
      selection models were observed. Marker density impacted the accuracy of
      prediction only marginally. Consequently, genomic selection of FHB resistance can
      be implemented most cost-efficiently based on low- to medium-density SNP arrays. 

PMID- 25388143
TI  - Self-help memory training for healthy older adults in a residential care center:
      specific and transfer effects on performance and beliefs.
AB  - BACKGROUND: Cognitive flexibility has repeatedly been shown to improve after
      training programs in community-dwelling older adults, but few studies have
      focused on healthy older adults living in other settings. OBJECTIVES: This study
      investigated the efficacy of self-help training for healthy older adults in a
      residential care center on memory tasks they practiced (associative and object
      list learning tasks) and any transfer to other tasks (grocery lists, face-name
      learning, figure-word pairing, word lists, and text learning). Transfer effects
      on everyday life (using a problem-solving task) and on participants' beliefs
      regarding their memory (efficacy and control) were also examined. With the aid of
      a manual, the training adopted a learner-oriented approach that directly
      encouraged learners to generalize strategic behavior to new tasks. The
      maintenance of any training benefits was assessed after 6 months. METHOD: The
      study involved 34 residential care center residents (aged 70-99 years old) with
      no cognitive impairments who were randomly assigned to two programs: the
      experimental group followed the self-help training program, whereas the active
      control group was involved in general cognitive stimulation activities. RESULTS:
      Training benefits emerged in the trained group for the tasks that were practiced.
      Transfer effects were found in memory and everyday problem-solving tasks and on
      memory beliefs. The effects of training were generally maintained in both
      practiced and unpracticed memory tasks. CONCLUSION: These results demonstrate
      that learner-oriented self-help training enhances memory performance and memory
      beliefs, in the short term at least, even in residential care center residents.

PMID- 25388144
TI  - Fe-promoted radical cyanomethylation/arylation of arylacrylamides to access
      oxindoles via cleavage of the sp(3) C-H of acetonitrile and the sp(2) C-H of the
      phenyl group.
AB  - Radical cyanomethylation/arylation of arylacrylamides to access oxindoles with
      acetonitrile as the radical precursor is described. This reaction involves dual C
      H bond functionalization, including the sp(3) C-H of acetonitrile and the sp(2) C
      H of the phenyl group. A variety of functional groups, such as methoxy, ethyloxy
      carbonyl, chloro, bromo, iodo, nitro, trifluoromethoxy and trifluoromethyl
      groups, are well tolerated. 

PMID- 25388146
TI  - MUSCLE: automated multi-objective evolutionary optimization of targeted LC-MS/MS
      analysis.
AB  - Developing liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses of
      (bio)chemicals is both time consuming and challenging, largely because of the
      large number of LC and MS instrument parameters that need to be optimized. This
      bottleneck significantly impedes our ability to establish new (bio)analytical
      methods in fields such as pharmacology, metabolomics and pesticide research. We
      report the development of a multi-platform, user-friendly software tool MUSCLE
      (multi-platform unbiased optimization of spectrometry via closed-loop
      experimentation) for the robust and fully automated multi-objective optimization
      of targeted LC-MS/MS analysis. MUSCLE shortened the analysis times and increased
      the analytical sensitivities of targeted metabolite analysis, which was
      demonstrated on two different manufacturer's LC-MS/MS instruments.

PMID- 25388145
TI  - GlycoRDF: an ontology to standardize glycomics data in RDF.
AB  - MOTIVATION: Over the last decades several glycomics-based bioinformatics
      resources and databases have been created and released to the public.
      Unfortunately, there is no common standard in the representation of the stored
      information or a common machine-readable interface allowing bioinformatics groups
      to easily extract and cross-reference the stored information. RESULTS: An
      international group of bioinformatics experts in the field of glycomics have
      worked together to create a standard Resource Description Framework (RDF)
      representation for glycomics data, focused on glycan sequences and related
      biological source, publications and experimental data. This RDF standard is
      defined by the GlycoRDF ontology and will be used by database providers to
      generate common machine-readable exports of the data stored in their databases.
      AVAILABILITY AND IMPLEMENTATION: The ontology, supporting documentation and
      source code used by database providers to generate standardized RDF are available
      online (http://www.glycoinfo.org/GlycoRDF/).

PMID- 25388147
TI  - What handedness and angles between helices has the studied three-helical protein
      domain?
AB  - We have created a new server FoldHandedness. Using this server it is possible:
      (i) to define the regions of helices from two issues (from the PDB file and using
      the last version of the DSSP program), (ii) to determine the handedness for any
      chosen three helices and (iii) to calculate the angle and sign between the chosen
      pairs of the helices for large proteins and complexes of proteins with DNA or
      RNA.

PMID- 25388149
TI  - MeRP: a high-throughput pipeline for Mendelian randomization analysis.
AB  - We present a Mendelian randomization (MR) pipeline (MeRP) to facilitate rapid,
      causal inference analysis through automating key steps in developing and
      analyzing genetic instruments obtained from publicly available data. Our tool
      uses the National Human Genome Research Institute catalog of associations to
      generate instrumental variable trait files and provides methods for filtering of
      potential confounding associations as well as linkage disequilibrium. MeRP
      generates estimated causal effect scores via a MR-score analysis using summary
      data for disease endpoints typically found in the public domain. We utilize our
      pipeline to develop genetic instruments for seven traits and evaluate potential
      causal relationships with two disease endpoints, observing two putatively causal
      associations between blood pressure and bone-mineral density with type 2
      diabetes. Our tool emphasizes the importance of careful but systematic screening
      of large datasets for discovery and systematic follow-up.

PMID- 25388148
TI  - Distinct profiling of antimicrobial peptide families.
AB  - MOTIVATION: The increased prevalence of multi-drug resistant (MDR) pathogens
      heightens the need to design new antimicrobial agents. Antimicrobial peptides
      (AMPs) exhibit broad-spectrum potent activity against MDR pathogens and kills
      rapidly, thus giving rise to AMPs being recognized as a potential substitute for
      conventional antibiotics. Designing new AMPs using current in-silico approaches
      is, however, challenging due to the absence of suitable models, large number of
      design parameters, testing cycles, production time and cost. To date, AMPs have
      merely been categorized into families according to their primary sequences,
      structures and functions. The ability to computationally determine the properties
      that discriminate AMP families from each other could help in exploring the key
      characteristics of these families and facilitate the in-silico design of
      synthetic AMPs. RESULTS: Here we studied 14 AMP families and sub-families. We
      selected a specific description of AMP amino acid sequence and identified
      compositional and physicochemical properties of amino acids that accurately
      distinguish each AMP family from all other AMPs with an average sensitivity,
      specificity and precision of 92.88%, 99.86% and 95.96%, respectively. Many of our
      identified discriminative properties have been shown to be compositional or
      functional characteristics of the corresponding AMP family in literature. We
      suggest that these properties could serve as guides for in-silico methods in
      design of novel synthetic AMPs. The methodology we developed is generic and has a
      potential to be applied for characterization of any protein family.

PMID- 25388150
TI  - Taxator-tk: precise taxonomic assignment of metagenomes by fast approximation of
      evolutionary neighborhoods.
AB  - MOTIVATION: Metagenomics characterizes microbial communities by random shotgun
      sequencing of DNA isolated directly from an environment of interest. An essential
      step in computational metagenome analysis is taxonomic sequence assignment, which
      allows identifying the sequenced community members and reconstructing taxonomic
      bins with sequence data for the individual taxa. For the massive datasets
      generated by next-generation sequencing technologies, this cannot be performed
      with de-novo phylogenetic inference methods. We describe an algorithm and the
      accompanying software, taxator-tk, which performs taxonomic sequence assignment
      by fast approximate determination of evolutionary neighbors from sequence
      similarities. RESULTS: Taxator-tk was precise in its taxonomic assignment across
      all ranks and taxa for a range of evolutionary distances and for short as well as
      for long sequences. In addition to the taxonomic binning of metagenomes, it is
      well suited for profiling microbial communities from metagenome samples because
      it identifies bacterial, archaeal and eukaryotic community members without being
      affected by varying primer binding strengths, as in marker gene amplification, or
      copy number variations of marker genes across different taxa. Taxator-tk has an
      efficient, parallelized implementation that allows the assignment of 6 Gb of
      sequence data per day on a standard multiprocessor system with 10 CPU cores and
      microbial RefSeq as the genomic reference data.

PMID- 25388152
TI  - GASS: identifying enzyme active sites with genetic algorithms.
AB  - MOTIVATION: Currently, 25% of proteins annotated in Pfam have their function
      unknown. One way of predicting proteins function is by looking at their active
      site, which has two main parts: the catalytic site and the substrate binding
      site. The active site is more conserved than the other residues of the protein
      and can be a rich source of information for protein function prediction. This
      article presents a new heuristic method, named genetic active site search (GASS),
      which searches for given active site 3D templates in unknown proteins. The method
      can perform non-exact amino acid matches (conservative mutations), is able to
      find amino acids in different chains and does not impose any restrictions on the
      active site size. RESULTS: GASS results were compared with those catalogued in
      the catalytic site atlas (CSA) in four different datasets and compared with two
      other methods: amino acid pattern search for substructures and motif and
      catalytic site identification. The results show GASS can correctly identify >90%
      of the templates searched. Experiments were also run using data from the
      substrate binding sites prediction competition CASP 10, and GASS is ranked fourth
      among the 18 methods considered.

PMID- 25388153
TI  - Lymphatic vessels: an emerging actor in atherosclerotic plaque development.
AB  - BACKGROUND: Atherosclerosis is a chronic inflammatory disease of large- to medium
      sized arteries and is the main underlying cause of death worldwide. The lymphatic
      vasculature is critical for processes that are intimately linked to atherogenesis
      such as the immune response and cholesterol metabolism. However, whether
      lymphatic vessels truly contribute to the pathogenesis of atherosclerosis is less
      clear despite increasing research efforts in this field. DESIGN: PubMed and Ovid
      MEDLINE databases were searched. In addition, key review articles were screened
      for relevant original publications. RESULTS: Current knowledge about lymphatic
      vessels in the arterial wall came from studies that examined the presence and
      location of such vessels in human atherosclerotic plaque specimens, as well as in
      a variety of arteries in animal models for atherosclerosis (e.g. rabbits, dogs,
      rats and mice). Generally, three experimental approaches have been used to
      investigate the functional role of plaque-associated lymphatic vessels;
      experimental lymphostasis was used to investigate lymphatic drainage of the
      arterial wall, and more recently, studies with genetic interventions and/or
      surgical transplantation have been performed. CONCLUSIONS: Lymphatic vessels seem
      to be mostly present in the adventitial layer of the arterial walls of animals
      and humans. They are involved in reverse cholesterol transport from
      atherosclerotic lesions, and arteries with a dense lymphatic network seem
      naturally protected against atherosclerosis. Lymphangiogenesis is a process that
      is an important part of the inflammatory loop in atherosclerosis. However, how
      augmenting or impeding the distribution of lymphatic vessels impacts disease
      progression remains to be investigated in future studies.

PMID- 25388154
TI  - Osteoporotic fracture models.
AB  - Animal models are widely used to investigate the pathogenesis of osteoporosis and
      for the clinical testing of anti-resorptive drugs. However, osteoporotic fracture
      models designed to investigate novel ways to treat fractures of osteoporotic bone
      must fulfil requirements distinct from those of pharmacological testing. Bone
      strength and toughness, implant fixation and osteointegration and fracture repair
      are of particular interest. Osteoporotic models should reflect the underlying
      clinical scenario be that primary type 1 (post-menopausal) osteoporosis, primary
      type 2 (senile) osteoporosis or secondary osteoporosis. In each scenario, small
      and large animal models have been developed. While rodent models facilitate the
      study of fractures in strains specifically established to facilitate
      understanding of the pathologic basis of disease, concerns remain about the
      relevance of small animal fracture models to the human situation. There is
      currently no all-encompassing model, and the choice of species and model must be
      individualized to the scientific question being addressed. 

PMID- 25388155
TI  - The expression and role of MEKK3 in renal clear cell carcinoma.
AB  - To explore the relationship between Mitogen-activated protein
      kinase/extracellular signal-regulated kinase kinase kinase 3(MEKK3) and cell
      apoptosis, clinicopathology, and prognosis, we characterize the expression of
      MEKK3, survivin and stat3 in renal clear cell carcinoma (RCCC). The expressions
      were measured by RT-PCR and Western blot from 15 cases of RCCC and 15 cases of
      control group (CG). Protein expression was detected by tissue microarray and
      immunochemistry in 98 cases of RCCC, 28 cases of CG. Expression patterns were
      analyzed for their association with pathological factors, correlation and
      prognosis in RCCC. Expression of MEKK3, survivin and stat3 mRNA was significantly
      higher in RCCC than in CG (P < 0.01). MEKK3, survivin and stat3 expression
      differed significantly between pathological grade (P < 0.05) and clinical stage
      (P < 0.05). MEKK3 expression was positively correlated with survivin and stat3 (P
      < 0.01). Furthermore, we investigated the role of MEKK3 in RCCC using the
      technique of RNA silencing via small interfering (siRNA) in ACHN cells. The
      results indicated that the targeted depletion of MEKK3 caused a dramatic massive
      apoptotic cell death. Kaplan-Meier survival analysis showed that MEKK3 and
      survivin expression, pathological grade, and clinical stage reduced cumulative
      survival. Cox multivariate regression analysis showed that MEKK3, survivin, and
      clinical staging were independent prognostic factors in renal cancer (P < 0.05).
      MEKK3 can be used as an important marker of prognostic evaluation in RCCC. The
      mechanism may be closely related to cell apoptosis. Targeted therapy of MEKK3 may
      provide a new strategy for treatment of chemotherapeutic-resistant tumors.

PMID- 25388151
TI  - EVpedia: a community web portal for extracellular vesicles research.
AB  - MOTIVATION: Extracellular vesicles (EVs) are spherical bilayered proteolipids,
      harboring various bioactive molecules. Due to the complexity of the vesicular
      nomenclatures and components, online searches for EV-related publications and
      vesicular components are currently challenging. RESULTS: We present an improved
      version of EVpedia, a public database for EVs research. This community web portal
      contains a database of publications and vesicular components, identification of
      orthologous vesicular components, bioinformatic tools and a personalized
      function. EVpedia includes 6879 publications, 172 080 vesicular components from
      263 high-throughput datasets, and has been accessed more than 65 000 times from
      more than 750 cities. In addition, about 350 members from 73 international
      research groups have participated in developing EVpedia. This free web-based
      database might serve as a useful resource to stimulate the emerging field of EV
      research. AVAILABILITY AND IMPLEMENTATION: The web site was implemented in PHP,
      Java, MySQL and Apache, and is freely available at http://evpedia.info.

PMID- 25388156
TI  - Glutathione and mitochondria determine acute defense responses and adaptive
      processes in cadmium-induced oxidative stress and toxicity of the kidney.
AB  - Cadmium (Cd(2+)) induces oxidative stress that ultimately defines cell fate and
      pathology. Mitochondria are the main energy-producing organelles in mammalian
      cells, but they also have a central role in formation of reactive oxygen species,
      cell injury, and death signaling. As the kidney is the major target in Cd(2+)
      toxicity, the roles of oxidative signature and mitochondrial function and
      biogenesis in Cd(2+)-related stress outcomes were investigated in vitro in
      cultured rat kidney proximal tubule cells (PTCs) (WKPT-0293 Cl.2) for acute
      Cd(2+) toxicity (1-30 uM, 24 h) and in vivo in Fischer 344 rats for sub-chronic
      Cd(2+) toxicity (1 mg/kg CdCl2 subcutaneously, 13 days). Whereas 30 uM Cd(2+)
      caused ~50 % decrease in cell viability, apoptosis peaked at 10 uM Cd(2+) in
      PTCs. A steep, dose-dependent decline in reduced glutathione (GSH) content
      occurred after acute exposure and an increase of the oxidized glutathione
      (GSSG)/GSH ratio. Quantitative PCR analyses evidenced increased antioxidative
      enzymes (Sod1, Gclc, Gclm), proapoptotic Bax, metallothioneins 1A/2A, and
      decreased antiapoptotic proteins (Bcl-xL, Bcl-w). The positive regulator of
      mitochondrial biogenesis Ppargamma and mitochondrial DNA was increased, and
      cellular ATP was unaffected with Cd(2+) (1-10 uM). In vivo, active caspase-3, and
      hence apoptosis, was detected by FLIVO injection in the kidney cortex of Cd(2+)
      treated rats together with an increase in Bax mRNA. However, antiapoptotic genes
      (Bcl-2, Bcl-xL, Bcl-w) were also upregulated. Both GSSG and GSH increased with
      chronic Cd(2+) exposure with no change in GSSG/GSH ratio and augmented expression
      of antioxidative enzymes (Gpx4, Prdx2). Mitochondrial DNA, mitofusin 2, and
      Pparalpha were increased indicating enhanced mitochondrial biogenesis and fusion.
      Hence, these results demonstrate a clear involvement of higher mitochondria copy
      numbers or mass and mitochondrial function in acute defense against oxidative
      stress induced by Cd(2+) in renal PTCs as well as in adaptive processes
      associated with chronic renal Cd(2+) toxicity.

PMID- 25388158
TI  - Palladium catalyzed Csp2-H activation for direct aryl hydroxylation: the
      unprecedented role of 1,4-dioxane as a source of hydroxyl radicals.
AB  - A novel strategy for direct aryl hydroxylation via Pd-catalysed Csp(2)-H
      activation through an unprecedented hydroxyl radical transfer from 1,4-dioxane,
      used as a solvent, is reported with bio relevant and sterically hindered
      heterocycles and various acyclic functionalities as versatile directing groups. 

PMID- 25388157
TI  - Effects of silica exposure on the cardiac and renal inflammatory and fibrotic
      response and the antagonistic role of interleukin-1 beta in C57BL/6 mice.
AB  - Current epidemiological studies suggest that crystalline silica exposure is
      associated with an increased risk of cardiovascular and renal disease; however,
      the potential pathological damage of the heart and kidney and its underlying
      mechanisms have not been completely elucidated. This study tried to investigate
      the silica-induced inflammatory and fibrotic changes in the heart and kidney and
      evaluate the role of interleukin (IL)-1 beta (beta) in silica-induced cardiac and
      renal damage. In this study, a silica-exposed model was generated by
      intratracheally instilling silica dust in mice. The anti-IL-1beta monoclonal
      antibody (mAb) was used to neutralise IL-1beta in the pulmonary alveolus and
      serum. The real-time PCR studies showed that (1) inhalational silica induced
      inflammatory responses in the heart and kidney by elevated mRNA levels of TNF
      alpha, IL-6 and MCP-1; (2) early fibrotic responses in the heart were observed as
      elevated mRNA levels of collagen I and fibronectin. What is more, fibrosis of the
      kidney was demonstrated by pathological results and significantly increased mRNA
      levels of TGF-beta, collagen I, collagen III and fibronectin. Further studies
      showed that usage of anti-IL-1beta mAb decreased the inflammatory response of the
      heart and kidney induced by inhalational silica and also attenuated fibrosis in
      the mouse kidney. In conclusion, this study found that inhaled silica induced
      inflammatory and early fibrotic responses in the mouse heart and inflammatory
      response and fibrosis in the mouse kidney. Neutralisation of IL-1beta attenuated
      the silica-induced inflammatory response of the heart and kidney and decreased
      fibrosis in the mouse kidney. 

PMID- 25388159
TI  - Erratum to "Influence of Vitamin D Binding Protein on Accuracy of 25
      Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay".
AB  - [This corrects the article DOI: 10.1155/2014/691679.]. 

PMID- 25388160
TI  - CheY's acetylation sites responsible for generating clockwise flagellar rotation
      in Escherichia coli.
AB  - Stimulation of Escherichia coli with acetate elevates the acetylation level of
      the chemotaxis response regulator CheY. This elevation, in an unknown mechanism,
      activates CheY to generate clockwise rotation. Here, using quantitative selective
      reaction monitoring mass spectrometry and high-resolution targeted mass
      spectrometry, we identified K91 and K109 as the major sites whose acetylation
      level in vivo increases in response to acetate. Employing single and multiple
      lysine replacements in CheY, we found that K91 and K109 are also the sites mainly
      responsible for acetate-dependent clockwise generation. Furthermore, we showed
      that clockwise rotation is repressed when residue K91 is nonmodified, as
      evidenced by an increased ability of CheY to generate clockwise rotation when K91
      was acetylated or replaced by specific amino acids. Using molecular dynamics
      simulations, we show that K91 repression is manifested in the conformational
      dynamics of the beta4alpha4 loop, shifted toward an active state upon mutation.
      Removal of beta4alpha4 loop repression may represent a general activation
      mechanism in CheY, pertaining also to the canonical phosphorylation activation
      pathway as suggested by crystal structures of active and inactive CheY from
      Thermotoga maritima. By way of elimination, we further suggest that K109
      acetylation is actively involved in generating clockwise rotation. 

PMID- 25388161
TI  - The NEDD8-activating enzyme inhibitor MLN4924 disrupts nucleotide metabolism and
      augments the efficacy of cytarabine.
AB  - PURPOSE: New therapies are urgently needed for patients with acute myelogenous
      leukemia (AML). The novel NEDDylation inhibitor MLN4924 (pevonedistat) has
      demonstrated significant preclinical antileukemic activity and preliminary
      efficacy in patients with AML in a phase I trial. On the basis of its antimyeloid
      and DNA-damaging properties, we investigated the ability of MLN4924 to augment
      conventional cytarabine (ara-C) therapy. EXPERIMENTAL DESIGN: The effects of
      MLN4924/ara-C on viability, clonogenic survival, apoptosis, DNA damage, and
      relevant pharmacodynamic targets were determined. The efficacy and
      pharmacodynamics of MLN4924/ara-C were assessed in an AML xenograft model.
      RESULTS: Cotreatment of AML cell lines and primary patient specimens with MLN4924
      and ara-C led to diminished clonogenic survival, increased apoptosis, and
      synergistic levels of DNA damage. RNAi demonstrated that stabilization of CDT-1,
      an event previously shown to mediate the DNA-damaging effects of MLN4924, was not
      a key regulator of sensitivity to the MLN4924/ara-C combination. Global metabolic
      profiling revealed that MLN4924 disrupts nucleotide metabolism and depletes
      intracellular nucleotide pools in AML cells. Subsequent experiments showed that
      MLN4924 promoted increased incorporation of ara-C into the DNA of AML cells. This
      effect as well as the therapeutic benefit of the MLN4924/ara-C combination was
      antagonized by supplementation with the nucleotide building block ribose.
      Coadministration of MLN4924 and ara-C to mice bearing FLT3-ITD(+) AML xenografts
      stably inhibited disease progression and increased DNA damage in vivo.
      CONCLUSIONS: Our findings provide strong rationale for clinical investigation of
      the MLN4924/ara-C combination and establish a new link between therapeutic
      inhibition of NEDDylation and alterations in nucleotide metabolism. Clin Cancer
      Res; 21(2); 439-47. (c)2014 AACR.

PMID- 25388162
TI  - Significant association of oncogene YAP1 with poor prognosis and cetuximab
      resistance in colorectal cancer patients.
AB  - PURPOSE: Activation of YAP1, a novel oncogene in the Hippo pathway, has been
      observed in many cancers, including colorectal cancer. We investigated whether
      activation of YAP1 is significantly associated with prognosis or treatment
      outcomes in colorectal cancer. EXPERIMENTAL DESIGN: A gene expression signature
      reflecting YAP1 activation was identified in colorectal cancer cells, and
      patients with colorectal cancer were stratified into two groups according to this
      signature: activated YAP1 colorectal cancer (AYCC) or inactivated YAP1 colorectal
      cancer (IYCC). Stratified patients in five test cohorts were evaluated to
      determine the effect of the signature on colorectal cancer prognosis and response
      to cetuximab treatment. RESULTS: The activated YAP1 signature was associated with
      poor prognosis for colorectal cancer in four independent patient cohorts with
      stage I-III disease (total n = 1,028). In a multivariate analysis, the impact of
      the YAP1 signature on disease-free survival was independent of other clinical
      variables [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.25-2.13; P <
      0.001]. In patients with stage IV colorectal cancer and wild-type KRAS, IYCC
      patients had a better disease control rate and progression-free survival (PFS)
      after cetuximab monotherapy than did AYCC patients; however, in patients with
      KRAS mutations, PFS duration after cetuximab monotherapy was not different
      between IYCC and AYCC patients. In multivariate analysis, the effect of YAP1
      activation on PFS was independent of KRAS mutation status and other clinical
      variables (HR, 1.82; 95% CI, 1.05-3.16; P = 0.03). CONCLUSIONS: Activation of
      YAP1 is highly associated with poor prognosis for colorectal cancer and may be
      useful in identifying patients with metastatic colorectal cancer resistant to
      cetuximab.

PMID- 25388164
TI  - A phase I monotherapy study of RG7212, a first-in-class monoclonal antibody
      targeting TWEAK signaling in patients with advanced cancers.
AB  - PURPOSE: Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and
      fibroblast growth factor-inducible molecule 14 (Fn14) are a ligand-receptor pair
      frequently overexpressed in solid tumors. TWEAK: Fn14 signaling regulates
      multiple oncogenic processes through MAPK, AKT, and NFkappaB pathway activation.
      A phase I study of RG7212, a humanized anti-TWEAK IgG1kappa monoclonal antibody,
      was conducted in patients with advanced solid tumors expressing Fn14.
      EXPERIMENTAL DESIGN: Dose escalations, over a 200- to 7,200-mg range, were
      performed with patients enrolled in weekly (QW), bi-weekly (Q2W), or every-three
      week (Q3W) schedules. Primary objectives included determination of dose and
      safety profile. Secondary endpoints included assessments related to inhibition of
      TWEAK: Fn14 signaling, tumor proliferation, tumor immune cell infiltration, and
      pharmacokinetics. RESULTS: In 192 treatment cycles administered to 54 patients,
      RG7212 was well-tolerated with no dose-limiting toxicities observed. More than
      95% of related adverse events were limited to grade 1/2. Pharmacokinetics were
      dose proportional for all cohorts, with a t1/2 of 11 to 12 days. Pharmacodynamic
      changes included clearance of free and total TWEAK ligand and reductions in tumor
      Ki-67 and TRAF1. A patient with BRAF wild-type melanoma who received 36 weeks of
      RG7212 therapy had tumor regression and pharmacodynamic changes consistent with
      antitumor effects. Fifteen patients (28%) received 16 or more weeks of RG7212
      treatment. CONCLUSION: RG7212 demonstrated excellent tolerability and favorable
      pharmacokinetics. Pharmacodynamic endpoints were consistent with reduced TWEAK:
      Fn14 signaling. Tumor regression was observed and prolonged stable disease was
      demonstrated in multiple heavily pretreated patients with solid tumors. These
      encouraging results support further study of RG7212. Clin Cancer Res; 21(2); 258
      66. (c)2014 AACR.

PMID- 25388163
TI  - Molecular pathways: translational and therapeutic implications of the Notch
      signaling pathway in cancer.
AB  - Over 100 years have passed since the first observation of the notched wing
      phenotype in Drosophila melanogaster, and significant progress has been made to
      characterize the role of the Notch receptor, its ligands, downstream targets, and
      cross-talk with other signaling pathways. The canonical Notch pathway with four
      Notch receptors (Notch1-4) and five ligands (DLL1, 3-4, Jagged 1-2) is an
      evolutionarily conserved cell signaling pathway that plays critical roles in cell
      fate determination, differentiation, development, tissue patterning, cell
      proliferation, and death. In cancer, these roles have a critical impact on tumor
      behavior and response to therapy. Because the role of Notch remains tissue and
      context dependent, alterations within this pathway may lead to tumor suppressive
      or oncogenic phenotypes. Although no FDA-approved therapies currently exist for
      the Notch pathway, multiple therapeutics (e.g., demcizumab, tarextumab, GSI MK
      0752, R04929097, and PF63084014) have been developed to target different aspects
      of this pathway for both hematologic and solid malignancies. Understanding the
      context-specific effects of the Notch pathway will be important for
      individualized therapies targeting this pathway.

PMID- 25388165
TI  - Podoplanin-positive cancer-associated fibroblasts in the tumor microenvironment
      induce primary resistance to EGFR-TKIs in lung adenocarcinoma with EGFR mutation.
AB  - PURPOSE: The biologic characteristics of microenvironmental constituents,
      especially cancer-associated fibroblasts (CAF), can be key regulators of the
      cellular sensitivity to molecular-targeted therapy. Epidermal growth factor
      receptor tyrosine kinase inhibitors (EGFR-TKI) have marked therapeutic effects
      against non-small cell lung cancer (NSCLC) with EGFR mutations, but some patients
      have exhibited primary resistance to EGFR-TKIs. We recently reported that
      podoplanin-positive fibroblasts are associated with a tumor-promoting phenotype
      of CAFs in lung adenocarcinoma. The aim of this study was to evaluate whether the
      susceptibility of NSCLC to EGFR-TKIs could be affected by podoplanin-expressing
      CAFs. EXPERIMENTAL DESIGN: We evaluated the EGFR-TKI sensitivity of EGFR-mutant
      lung adenocarcinoma cell lines cocultured with podoplanin-expressing CAFs. We
      also examined the association between the expression of podoplanin in CAFs in
      surgical specimens and EGFR-TKI response of postoperative recurrent patients with
      EGFR mutations (N = 106). RESULTS: Lung adenocarcinoma cell lines became more
      resistant to EGFR-TKI when cocultured with podoplanin-expressing CAFs, compared
      with control CAFs in vitro. The knockdown of podoplanin expression on CAFs
      cancelled the resistance to EGFR-TKIs in cancer cells. Compared with control
      CAFs, the cancer cells that were cocultured with podoplanin-positive CAFs
      continued to exhibit significantly higher p-ERK levels after treatment with
      gefitinib. Furthermore, postoperative recurrent patients with podoplanin-positive
      CAFs had a significantly lower overall response rate to EGFR-TKIs compared with
      those with podoplanin-negative CAFs (53% vs. 83%; P < 0.01). CONCLUSIONS:
      Podoplanin-positive CAFs play an important role in primary resistance to EGFR
      TKIs and may be an ideal therapeutic target for use in combination therapy with
      EGFR-TKIs.

PMID- 25388166
TI  - Deregulation of the PP2A inhibitor SET shows promising therapeutic implications
      and determines poor clinical outcome in patients with metastatic colorectal
      cancer.
AB  - PURPOSE: SET is an endogenous PP2A inhibitor that might represent a novel
      molecular target for antitumor therapy. The aim of this study was to evaluate the
      molecular effects of SET deregulation and its potential clinical significance in
      metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: We studied the biologic
      effects of SET on cell growth, colonosphere formation, caspase activity, PP2A
      activation status, and sensitivity to oxaliplatin and FTY720 treatments.
      Moreover, we analyzed SET expression by immunostaining in 242 patients with mCRC.
      RESULTS: SET deregulation promotes cell growth and colonosphere formation and
      inhibits PP2A, thereby impairing its antitumor effects. Moreover, SET reduces
      sensitivity to oxaliplatin in colorectal cancer cell lines, which is restored
      after FTY720 treatment. SET overexpression was detected in 24.8% (60 of 242) of
      patients with mCRC and determined significantly shorter overall (8.6 vs. 27
      months; P < 0.001) and progression-free survival (7.1 vs. 13.7 months; P <
      0.001), and poor response to oxaliplatin-based chemotherapy (P = 0.004).
      Interestingly, its prognostic value was particularly evident in patients younger
      than 70 years and in those harboring KRAS mutations. CONCLUSIONS: SET
      overexpression is a frequent event in mCRC that plays a potential oncogenic role
      associated with worse outcome and resistance to oxaliplatin. Moreover, this
      alteration defines a subgroup of patients who could benefit from therapies
      containing PP2A activators such as FTY720.

PMID- 25388167
TI  - A phase I study of PF-04449913, an oral hedgehog inhibitor, in patients with
      advanced solid tumors.
AB  - PURPOSE: To estimate the maximum tolerated dose (MTD) of single-agent PF
      04449913, and to evaluate safety, tolerability, pharmacokinetics,
      pharmacodynamics, and preliminary antitumor activity in patients with advanced
      tumors. EXPERIMENTAL DESIGN: A 3+3 design was used in this open-label,
      multicenter, phase I study and dose escalation/de-escalation applied until
      identification of the MTD. PF-04449913 was orally administered once daily in
      continuous 28-day treatment cycles. The starting dose was 80 mg. RESULTS: A total
      of 23 patients were enrolled; 19 were evaluable for first-cycle dose-limiting
      toxicity (DLT). The first-cycle DLT rate at the 640 mg dose level was 33.3%, and
      the MTD was estimated to be 320 mg once daily. The recommended phase II dose was
      not determined. PF-04449913 was generally well tolerated at doses of 80 to 320 mg
      once daily. The most common treatment-related adverse events (AE) were grade 1-2
      dysgeusia, fatigue, decreased appetite, nausea, dizziness, dehydration, and
      diarrhea. Treatment-related grade 3 AEs only occurred in patients receiving PF
      04449913 640 mg once daily. No treatment-related grade 4-5 AEs were reported.
      Pharmacokinetic analysis indicated a generally dose-proportional kinetics with
      biphasic elimination, supporting once-daily dosing. PF-04449913 modulated
      hedgehog signaling at the dose levels tested, as demonstrated by >80%
      downregulation of GLI1 expression in the skin of treated patients. Eight patients
      (34.8%) achieved stable disease; none had complete or partial response. Three
      patients with disease progression at enrollment had prolonged disease
      stabilization (>=6 months). CONCLUSIONS: The results obtained in this study
      support further evaluation of PF-04449913 in patients with advanced solid tumors.

PMID- 25388169
TI  - Implementation and challenges facing occupational health surveillance.

PMID- 25388168
TI  - Gene dosage effects in 46, XY DSD: usefulness of CGH technologies for diagnosis.

PMID- 25388170
TI  - The gap between what has been defined and what is still pending in occupational
      health surveillance.
AB  - The scope of this paper is to address some questions about Occupational Health
      Surveillance (VISAT) in Brazil based on various elements of analysis, in order to
      contribute to the debate on this theme at the Fourth National Conference on
      Occupational Health. The topics discussed in the article are: the role of
      Reference Centers for Occupational Health (CEREST) as a place for discussing
      VISAT; training and qualification of the VISAT agents; commitment of workers as
      subjects of VISAT action; strategies for intersectorial liaison with other areas
      of the State; and the dialogue between peers working in the field of research and
      action of VISAT. It should be emphasized that in Brazil there is specific
      legislation on VISAT that is a priority of the National Labor Policy. The
      conclusion drawn is that heavy investment in the training of agents and the
      development of specific guidelines is needed to implement systematic and
      intersectorial actions in this respect. At the time of the Conference, the
      greatest expression of the exercise of social control, it is recommended that the
      participation in surveillance procedures of health workers be evaluated as a
      precondition to ensure the effectiveness of these actions. 

PMID- 25388171
TI  - [Work process and working conditions in poultry processing plants: report of a
      survey on occupational health surveillance].
AB  - This article presents the report of a survey on health surveillance activities
      performed in poultry processing plants in the south of Brazil. It aims to
      contribute to an understanding of the work process developed, the growth of the
      sector, the organization of labor and the confrontation with the economic model
      of this sector, which has been exposing employees to working conditions that
      undermine their health. The working conditions identified are considered largely
      incompatible with health and human dignity. The study supports interinstitutional
      intervention, especially with the Public Ministry of Labor, criticizes the weak
      implementation of specific government interventions in health conditions in the
      industry and introduces the new Regulatory Standard 36 as a positive perspective
      for the near future.

PMID- 25388172
TI  - [Exposure to benzene in gas stations in Brazil: occupational health surveillance
      (VISAT) network].
AB  - The scope of this article is to present the surveillance network's experience of
      exposure to benzene in gas stations, describing its components developed in the
      Unified Health System. It is a report and analysis of the experience of
      monitoring and its impact on the health of gas station workers in six Brazilian
      states. It presents the prospect of action, operated by the circulation of
      information, national meetings, discussions of specific strategies and shared
      experiences, methodologies and common tools. Inspection procedures, individual
      assessments and training are described. Risk situations and occupational and
      environmental exposure were identified in 1,311 gas stations and 564 workers were
      assessed. Forecourt attendants, superintendents and measuring, offloading and
      testing employees were all exposed. The integrated and complementary features of
      this surveillance, implemented in the occupational and environmental areas,
      suggest intervention in a broader and network-linked territory. The intervention
      would transcend fragmentation between individual and collective practices,
      services and education, becoming an example of action for assessment and
      mitigation of the impact on health workers, the articulation of action in health,
      the environment and intersectorial connection.

PMID- 25388173
TI  - The issue of mental health in occupational health surveillance.
AB  - This paper addresses the issue of mental health in the Occupational Health
      Surveillance (VISAT) context. It seeks to present theoretical aspects and
      institutional policies contributing to the incorporation of mental health
      dimensions into the VISAT process, in view of the pressing need to attend to this
      demand that is becoming increasingly important in the occupational health area,
      especially within the scope of the National Comprehensive Occupational Healthcare
      Network (RENAST). Some theoretical approaches and practical experiences in mental
      health and work are systematically presented and discussed in this essay. A
      survey is also conducted of potential strategies to integrate mental health into
      VISAT actions. It is our view that the origins of illnesses and ensuing harm are
      closely linked to the elements involved in work organization and management.
      Consequently, surveillance practices should include and identify generating
      components of these negative aspects. The diversity of illnesses caused by work
      processes and conditions calls for major investment to ascertain and change the
      situations that give rise to such illnesses. 

PMID- 25388174
TI  - [Surveillance experience in the sugarcane sector: challenges in disrupting the
      perilous "marathon" of the sugarcane plantations].
AB  - The sugar-alcohol sector is growing year by year, especially in the state of Sao
      Paulo where approximately 42.9% of the sugar-ethanol plants are concentrated. The
      production chain is a subject for concern to public agencies and to civil society
      by exposing migrant workers to risks arising from the work process. In Sao Paulo,
      from 2006-2009, Occupational Health Surveillance (VISAT) set up two initiatives
      to address problems related to the housing and working conditions of sugarcane
      workers. The objective of this article presented in the form of an essay is to
      analyze the experiences in their context. The methodology used combines document
      analysis with the perception of the authors who participated in the actions. The
      experience led to improvements in these conditions and fostered public debate on
      the conditions of such physically demanding work. The interventions resulted in a
      definition of sanitary norms and initiatives at the legislative and judicial
      level, but even the most successful measures failed to attain the organizational
      targets, especially a production remuneration structure that challenges the
      traditional action of surveillance and the impacts were weakened due to the
      fragility of worker representation for the sector.

PMID- 25388175
TI  - [Surveillance on pesticides: quantification of use and prediction of impact on
      health, work and the environment for Brazilian municipalities].
AB  - This paper analyzes the quantity, type and toxicity of pesticides used per
      hectare in the State of Mato Grosso as a surveillance strategy for the health of
      workers, the population in general and the environment, and to serve as a
      surveillance indicator for Brazilian cities. Brazil cultivated 95 million
      hectares in 2012, and Mato Grosso was the major consumer of pesticides. In this
      research, the database of the Agriculture and Livestock Defense Institute was
      consulted, as it records the prescribed agronomic data and place of use in sales
      invoices. The results reveal the average consumption of pesticides per hectare
      per crop: 12 liters for soy; 6 liters for corn; 4.8 liters for sugarcane; and 24
      liters for cotton. The toxicological types and classes of pesticides used per
      hectare per crop were also monitored. Using a matrix of agricultural production
      and pesticide consumption, it was also found that certain health problems are
      correlated with the major producing regions. Based on pesticide consumption,
      agricultural production and pesticide toxicity it is possible to ascertain health
      problems in Brazilian cities and establish prevention and surveillance strategies
      for the workers, the environment and the populations exposed to pesticides.

PMID- 25388176
TI  - [Model of Analysis and Prevention of Accidents - MAPA: tool for operational
      health surveillance].
AB  - The analysis of work-related accidents is important for accident surveillance and
      prevention. Current methods of analysis seek to overcome reductionist views that
      see these occurrences as simple events explained by operator error. The objective
      of this paper is to analyze the Model of Analysis and Prevention of Accidents
      (MAPA) and its use in monitoring interventions, duly highlighting aspects
      experienced in the use of the tool. The descriptive analytical method was used,
      introducing the steps of the model. To illustrate contributions and or
      difficulties, cases where the tool was used in the context of service were
      selected. MAPA integrates theoretical approaches that have already been tried in
      studies of accidents by providing useful conceptual support from the data
      collection stage until conclusion and intervention stages. Besides revealing
      weaknesses of the traditional approach, it helps identify organizational
      determinants, such as management failings, system design and safety management
      involved in the accident. The main challenges lie in the grasp of concepts by
      users, in exploring organizational aspects upstream in the chain of decisions or
      at higher levels of the hierarchy, as well as the intervention to change the
      determinants of these events.

PMID- 25388177
TI  - Health of subsistence fishermen and challenges for Occupational Health
      Surveillance.
AB  - There are approximately a million subsistence fishermen in Brazil whose
      activities expose them to severe occupational hazards without adequate health
      protection. This article conducts an analysis of working conditions and health
      risks faced by subsistence fishermen and outlines challenges to the
      implementation of Occupational Health Surveillance (VISAT) actions. The
      methodology is based on qualitative analysis of risks and working conditions
      through observation and interviews, and diagnosis of occupational illnesses with
      clinical evaluation. Mobile teams conducted eight years of activities together
      with fishing communities throughout the state of Bahia. The results revealed the
      challenge of surveying a traditional self-employed category with relative
      management autonomy. Fishermen face precarious living conditions without access
      to occupational health services. They are exposed to thirty work-related
      illnesses without protection, diagnosis, treatment and social security coverage.
      The conclusion reached is that there is a need for intersectorial VISAT action to
      reduce excessive working hours, organization of the Unified Health System (SUS)
      for acknowledgement of occupational illnesses and guaranteeing social security
      rights through actions focused on health education.

PMID- 25388178
TI  - "Dual causation accident": a third type of work-related accident and its
      importance for occupational health surveillance.
AB  - The scope of this study is to contribute to the improvement of Occupational
      Health Surveillance in the Unified Health System (UHS), through the recognition
      and inclusion of a third type of work-related accident in the current Brazilian
      legislation classification: the dual causation accident. This classification aims
      at facilitating the establishment of a causal connection, thus broadening the
      understanding of the relationship between work process and the production of
      diseases. It also aims at improving legal rules to protect the health of workers.
      This approach, besides enabling the identification of sentinel events (starting
      point of surveillance activities), might contribute not only to a decrease in
      underreporting of work-related accidents, but also to the uniformity of concepts
      and the implementation of integrated actions of the National Social Security
      Institute (NISS), the UHS, the Ministry of Labor (MLE) and the Judiciary for the
      protection of workers. To propose a third type of occupational accident, a study
      of occupational accidents and causes of underreporting was conducted, with
      reference to the Brazilian labor legislation in the context of the National
      Policy on Occupational Health and the UHS.

PMID- 25388179
TI  - Health surveillance and agribusiness: the impact of pesticides on health and the
      environment. Danger ahead!
AB  - Pesticides are abundantly used in agribusiness and can be damaging to health and
      the environment. Society in general and agricultural, environmental and health
      institutions in particular have a legal and statutory duty to supervise their
      use. To identify and analyze these actions, interviews were conducted with
      managers of the municipal offices and union leaders representing the workers and
      farmers. Managers and rural producers were of the opinion that pesticides are
      essential to productivity and do not generate any impact on health and the
      environment. No policies or institutional relations monitoring pesticide use were
      identified or being considered. Rural workers' unions do not take any political
      initiatives to benefit the health of the workers themselves, their families and
      that of society in general. The conclusion draws is the pressing need to develop
      a model for sustainable agriculture, healthy and free of pesticides and that
      organized society and responsible institutions must undertake actions that meet
      the needs of the people who working on the farms or consume the agricultural
      products harvested there, especially controlling risks and consequences that can
      and must be avoided.

PMID- 25388180
TI  - [Assessment of the prevalence of burnout syndrome in community health agents of
      the city of Aracaju in the state of Sergipe, Brazil].
AB  - The Community Health Worker Program was established in 1991 with the aim of
      contributing to improving the quality of life of the population, with the
      community health workers being the program's protagonists. In line with this,
      this study aimed to evaluate the prevalence of burnout syndrome in the community
      health workers in Aracaju. Data collection was conducted among 222 community
      health workers in 43 family health units in Aracaju. The research instruments
      were: identification sheets produced by the authors of the research to verify the
      occupational and socioeconomic situation of the professionals; Job Stress Scale
      Questionnaires and the Maslach Burnout Inventory. The results showed that in
      relation to exposure to stress, 57.2% experienced psychological pressure and
      marked job control; 10.8% of community health workers showed a moderate tendency
      to Burnout Syndrome and 29.3% manifested characteristics equivalent to the
      syndrome. These characteristics of burnout syndrome may be related to frustration
      with respect to inefficacy in resolving the problems and the close involvement of
      community health workers with their community. Given these facts, it is necessary
      to create intervention strategies that seek to prevent the psychosocial problems
      encountered in these health professionals.

PMID- 25388181
TI  - [Musculoskeletal pain and occupational vulnerability in municipal public sector
      workers in Belo Horizonte, Brazil].
AB  - This article seeks to describe the profile of workers in the municipal public
      sector in relation to the occurrence of self-reported musculoskeletal pain (MSP).
      In 2009, a cross-sectional study was conducted in Belo Horizonte that assessed
      sociodemographic characteristics, functional health status, habits and quality of
      life, through a self-applied questionnaire. We used the Grade of Membership
      method (GoM) to define the profiles and the degree of belonging to each
      particular profile. Three reference profiles were identified: worker with pain;
      worker without pain, non-respondents. Given the reference profiles, the typology
      of association between work and self-reported occurrence of MSP classified 89.9%
      of the sample. The typology was organized into five profiles: mixed (4.1%); sick
      worker (12.0%); worker more vulnerable to MSP (16.9%); worker less vulnerable to
      MSP (22.6%); healthy worker (34.3%). The analysis made it possible to clarify the
      connections between MSP and the physical and psychosocial factors at work in the
      municipal public service, indicating avenues for further reflection on the
      inequities in musculoskeletal health and occupational vulnerability. 

PMID- 25388182
TI  - [Burnout syndrome in primary health care professionals].
AB  - Burnout is characterized by emotional exhaustion, depersonalization and low
      occupational performance, which may occur among health professionals. This
      article evaluates burnout among workers in Primary Health Care (PHC) in three
      small towns in the Zona da Mata Mineira. The study analyzes associations by
      logistic regression between burnout, socioeconomic, and demographic aspects of
      work. A total of 149 professionals were selected, 107 of these responded to all
      questionnaires. To measure burnout, the Maslach Burnout Inventory (MBI) was used
      and to characterize the professional, a questionnaire assessing three different
      issues - namely individual and sociodemographic aspects and team area coverage -
      was used. 101 professionals were classified with positive indication for burnout.
      The variables present in the backward stepwise logistic regression model
      positively associated with indicative of burnout were: being younger than the
      population average (> 29.5 years) and use of drugs, including sedatives,
      tranquilizers and sleeping pills. The results contribute to the identification of
      factors associated with burnout and therefore highlight the need for more
      detailed investigation.

PMID- 25388183
TI  - [Work as a promoter of health].
AB  - Studies on the relation between health and work tend to highlight the negative
      and pathological aspects, as if work produces only sickness and alienation. On
      the contrary, our proposal is to stress how work can also produce health. Based
      on Canguillem's concept of health, and from the contributions of the so-called
      "work clinics", we intend to analyze the purpose of work as a promoter of health.
      Canguilhem affirms that health is not adaptive, as such it does not involve
      adapting well to the world, but to the creation of tenets of life. For their
      part, the work clinics provide tools to approximate us to the know-how-to-do
      produced by workers in their daily work, namely not only how workers adapt to
      work, but how they create and recreate it permanently Thus, we can think work as
      a promoter of health where there is room for collective and personal creation, as
      well as recognition of workers in their activity.

PMID- 25388184
TI  - Urinary lithiasis in civil construction workers as a management indicator for
      health and improvement in personnel.
AB  - INTRODUCTION: Empirical information provided by health care professionals acting
      in the first line of care report a constant increase in the number of civil
      construction workers that present painful acute conditions, in most cases
      associated with the existence of urinary tract calculi. AIMS: Evaluating the
      prevalence of urinary lithiasis in civil construction workers, as a means to
      identify indicators for the management of health and personnel. METHODS:
      Observational study based on directed questionnaire. RESULTS: From the 94
      participants, 18 (19%) were lithiasic, mostly due to overweight and reduced fluid
      intake. CONCLUSION: The observed prevalence appeared to be two times greater than
      that of the general population. Thus, prevention for such condition gains
      relevance, in order to avoid discomfort for the worker, and also reduce costs due
      to absenteeism, improving productivity, benefiting the workers by performance and
      creating the perspective of an improved quality of life.

PMID- 25388185
TI  - [Towards a two-dimensional study of burnout syndrome in college students].
AB  - A literature review was conducted with a view to propose a new definition for
      burnout syndrome (BS) among university students, as a two-dimensional syndrome,
      where the two essential or core dimensions of BS are student exhaustion and
      student apathy and disinterest. It eliminates the third dimension of efficacy or
      academic self-efficacy in the specific case of students for not meeting the
      situational and conceptual requirements of the syndrome per se.

PMID- 25388186
TI  - Impact of oral health conditions on the quality of life of workers.
AB  - Occupational health has been the scope of numerous studies, primarily due to the
      concern that the worker should enjoy good working conditions and a satisfactory
      quality of life. This study seeks to analyze the impact of oral health on the
      quality of life of workers at a public university using the simplified version of
      the Oral Health Impact Profile (OHIP-14) and associated factors. A cross
      sectional study was conducted with 326 workers who responded the questions of
      OHIP-14 about self-rated health, oral morbidity, and socioeconomic and
      demographic questions. Multiple linear regression analysis was performed to
      verify the association between the independent variables and OHIP-14. About 40%
      of the impact of oral health on quality of life can be explained by the
      variables: education level (p = 0,03), age (p = 0,03), reason for visiting a
      dentist (p = 0,01), oral health perception (p < 0,01) and satisfaction with teeth
      and mouth (p < 0,01). The use of OHIP-14 can be useful for planning programs and
      actions focused on health education for occupational health, prioritizing workers
      with greater psychosocial impacts caused by oral problems. 

PMID- 25388187
TI  - [Work context and the human cost of work in a Brazilian judiciary organ].
AB  - In recent years, in order to ensure the effectiveness of justice, the process of
      reform of the Brazilian Judiciary began. If, on the one hand, the changes have
      been significant and positive, on the other, little is known about the impact of
      the changes on the worker. In order to give visibility to the effects of these
      changes, based on the theory of the ergonomics of the activity, the scope of this
      research was to evaluate the Work Context and the Human Cost of Work in a
      Brazilian Judiciary Organ. The Assessment Scale of Work Context (ASWC) and the
      Scale of Human Cost of Work (SHCW) were used, as they are both components of the
      Inventory on Work and Risk - IWR. The study included 383 staff in different
      locations: 58% female, 62.7% with postgraduate qualifications, 59.3% married and
      53% between 21 and 40 years of age. The results in ASWC reveal critical factors
      in work organization and socio-professional relations. In the case of SHCW,
      Affective Cost and Cognitive Cost factor assessments were moderate to critical.
      The ANOVA revealed differences in perceptions related to some socio-demographic
      variables.

PMID- 25388188
TI  - [Tobacco cultivation in the south of Brazil: green tobacco sickness and other
      health problems].
AB  - The scope of this study was to identify the presence of health problems and their
      significance for tobacco harvesters, State representatives, civil society and the
      tobacco industry, and also understand their coping strategies. An ethnographic
      study with 35 semi-structured interviews answered by harvesters' families and key
      informants was carried out in a rural community in the state of Rio Grande do
      Sul. In addition to that, participant observation of the families was conducted.
      The harvesters and representatives of civil society acknowledge the presence of
      green tobacco sickness and other problems. Representatives of healthcare
      organizations do not identify or recognize the sickness as being a consequence of
      the productive activity linked to tobacco. Tobacco industry representatives
      acknowledge that there are health problems, but blame the harvesters. The
      conclusion reached is that there is a need for a closer approach, monitoring and
      intervention by Public Authorities in tobacco-producing rural communities,
      seeking to develop surveillance actions and promote occupational health. 

PMID- 25388189
TI  - A study of the status of exposure to polycyclic aromatic hydrocarbons (PAHs) in
      relation to its metabolites among workers in a Korean chemical factory.
AB  - The study was conducted to evaluate the status of worker exposure to polycyclic
      aromatic hydrocarbons (PAHs) through the measurement of urinary metabolites such
      as 1-hydroxypyrene (OHP) and 2-naphthol. A survey using a questionnaire involving
      326 workers with measurement of urinary metabolites of 1-OHP and 2-naphthol was
      conducted. The differences in urinary 1-OHP and 2-naphthol concentrations, and
      changes in work, smoking habits and lifestyle were analyzed. The number of male
      subjects was 314 (96.3%), the largest age group was the fifth decade (170 cases,
      52.1%). The urinary 1-OHP and 2-naphthol concentrations were significantly higher
      in the production workers. The urinary 1-OHP and 2-naphthol concentrations were
      significantly higher in smokers. In a multiple regression model, log (1-OHP)
      increased in smokers and production workers, while log (2-naphthol) only
      increased in smokers. Our results suggest that workers in this factory were
      exposed to PAHs from non-occupational as well as occupational sources. The
      occupational exposure to PAHs can be reduced through the improvement of the
      process, but the exposure due to smoking can be prevented only by giving up
      smoking.

PMID- 25388190
TI  - [Work overload faced by caregivers assisting frequenters of a psychosocial care
      center for children and adolescents in the south of Brazil].
AB  - The scope of this article is to compare the work overload averages among
      caregivers assisting frequenters of a Psychosocial Care Center for children and
      adolescents (CAPSi) in Pelotas-Brazil in relation to the mental health of the
      children and adolescents and the caregivers themselves. It involved a cross
      sectional study conducted with the primary caregiver of CAPSi frequenters. The
      work overload was evaluated using the Zarit Burden Interview scale and the mental
      health problems of frequenters were assessed using the Strengths and Difficulties
      Questionnaire (SDQ). To verify the presence of common potential mental disorders
      of caregivers, a Self-Report Questionnaire (SRQ-20) was used. T-test and ANOVA
      was used for data analysis. The average work overload was significantly higher in
      caregivers of frequenters with behavioral problems (p = 0.000), hyperactivity (p
      = 0.001) and relationship problems with peers (p = 0.001). IT was also
      significantly higher among those classified as potential cases of common mental
      disorders (p = 0.000); women caregivers (p = 0.032) and those with past problems
      with the Judiciary and/or Guardianship Council involving a frequenter (p =
      0.039). The importance of work geared to caregivers to enhance the quality of
      care and quality of life of the caregivers themselves should be highlighted. 

PMID- 25388191
TI  - [The challenges of citizenship and participation in the health systems].
AB  - The themes of citizen participation and citizenship have assumed great relevance
      in public policy in most countries of the world. In this article, after briefly
      summarizing the main stages of development of the concept of citizenship, the
      prominence of social participation as a practice of citizenship will be depicted.
      Next, the potential and limits of deliberative approaches established to promote
      new strategies of citizens' participation in health will be analyzed. The paper
      will then focus on critical aspects that contribute to reducing or hindering the
      exercise of citizenship rights, including: the issue of representation
      underpinning the citizen participation methods; the issue of the influence of
      participatory devices in decision-making processes; and the limited experience
      and interest in assessing the effectiveness of citizen participation in the
      health sector.

PMID- 25388192
TI  - The evolution of the federal funding policies for the public health surveillance
      component of Brazil's Unified Health System (SUS).
AB  - Health surveillance (HS) is one of the key components of the Brazilian Unified
      Health System (SUS). This article describes recent changes in health surveillance
      funding models and the role these changes have had in the reorganization and
      decentralization of health actions. Federal law no. 8.080 of 1990 defined health
      surveillance as a fundamental pillar of the SUS, and an exclusive fund with
      equitable distribution criteria was created in the Basic Operational Norm of 1996
      to pay for health surveillance actions. This step facilitated the
      decentralization of health care at the municipal level, giving local authorities
      autonomy to plan and provide services. The Health Pact of 2006 and its regulation
      under federal decree No. 3252 in 2009 bolstered the processes of
      decentralization, regionalization and integration of health care. Further changes
      in the basic concepts of health surveillance around the world and in the funding
      policies negotiated by different spheres of government in Brazil have been
      catalysts for the process of HS institutionalization in recent years.

PMID- 25388193
TI  - Primary health care assessment tools: a literature review and metasynthesis.
AB  - This study comprises a systematic review and metasynthesis of qualitative
      literature on national and international databases to identify the main tools
      used to assess Primary Health Care (PHC). A total of 3,048 results were returned
      for literature written in Portuguese, Spanish and English published between 1979
      and 2013. Thirty-three articles/studies were selected after thorough reading and
      analysis. Eight of these studies addressed the use of one or more of the
      following validated PHC assessment tools: the WHO Primary Care Assessment Tool
      (PCET); the ADHD Questionnaire for Primary Care Providers (AQ-PCP); the General
      Practice Assessment Questionnaire (GPAQ), PACOTAPS (primary health care
      software); and the PCAT (Primary Care Assessment Tool). The study showed that the
      majority of these tools were used internationally. The PCAT and EUROPEP were used
      in Brazil and the most commonly used tool in this country was the PCAT. The
      results show that the use of research tools to assess PHC may assist in the
      creation of new proposals to improve family healthcare and that PCAT is the most
      adequate tool for this purpose.

PMID- 25388194
TI  - A pattern of adult involvement in highway acidentes.
AB  - This study aimed to identify the set of circumstances that contributed to the
      involvement of adults in traffic accidents. The study was of the cross-sectional
      type using secondary data. The patterns were identified through cluster analysis
      using a method called Hierarchical Ascendant Classification. Five classes were
      identified. Three classes involved males with minor injuries resulting from
      accidents between vehicles or vehicle-object, during the daytime and with dry
      road surface conditions. Two classes involved females, resulting in severe
      injuries, and were notable for occurring during the night and with a lower rate
      of use of seat belts. The findings of this study, especially in relation to the
      more serious accidents involving the female drivers, draw attention to this
      situation and point to a need for further studies involving these classes, which
      are increasingly common in traffic patterns.

PMID- 25388195
TI  - Resilience and death: the nursing professional in the care of children and
      adolescents with life-limiting illnesses.
AB  - The purpose of this article is to analyze the resilience of the nursing staff in
      providing care for children and adolescents with chronic diseases, including
      coping with their deaths. The participants of this qualitative research were
      nursing professionals working in the pediatric ward of a hospital in the city of
      Rio de Janeiro, Brazil. The data collection was obtained by applying the
      resilience scale, by returning the scales in groups, and by semi-structured
      interviews. The relationship between professional resilience and coping with the
      process of children and adolescent's deaths stood out in the analysis based on
      data obtained from group and individual interviews. The care given to children
      and adolescents with life-limiting illnesses triggers resilience-related answers
      concerning alternatives that oscillate between individual reactions (religious
      and psychological support), and the search for an incipient collective support
      based on personal relationships. This study points out that this subject must be
      strategically handled to train this professional, who must be able to rely on
      support from the collective environment, presumed within the professional health
      care training and in the management of humanization at the hospital.

PMID- 25388196
TI  - The interaction of several fields of knowledge for the articulation of collective
      oral health actions: the mapping of a family health team.
AB  - This paper maps the experience of a family health team (FHT) in the creation of a
      knowledge and responsibility field to practice Oral Health (OH). Institutional
      analysis was used to establish the theoretical and methodological framework,
      supported by the concept analyzers, implication analysis, territorialization and
      deterritorialization. Cartography was used to monitor the procedures and the
      order of events and to facilitate understanding. The subjects were members of an
      FHT in a training context. Data production took place during the FHT meetings on
      administrative and family discussion matters. The case study presented here was
      one of the research analyzers. As results, the process of building the case study
      was identified, which revealed how the FHT took the family into care; the
      movements broadening the perspective of care, finding ways for disciplinary
      interactions in order to construct a collective OH approach, which emerged from
      the day-to-day tensions of the FHT work process. The conclusion reached is that
      this case study revealed the stresses involved in the process of deconstruction
      of dental assistance and the movement towards the interaction of several fields
      of knowledge and practices for the production of care from the perspective of OH
      attention.

PMID- 25388197
TI  - [Descriptive study about social and demographical characteristic of the
      disability in Latin America].
AB  - The objective of this study was to ascertain the social and demographical
      characteristics of disability in Latin America and verify the methodology used in
      the survey by questionnaires for the analysis of disabilities. It is a
      descriptive study that analyzed the data and methodology of disability surveys
      conducted in Latin America after 2001. It was noted that there is a big
      difference in the prevalence of disability found in the surveys that used the
      International Classification of Functioning, Disability and Health (ICF) for
      statistical analysis of people with disabilities. It was also shown that in Latin
      America motor disabilities are more prevalent in men over 65 years old and with a
      low educational level. The main cause is chronic disease. The conclusion is that
      ICF is a good methodological tool to use in disability survey questionnaires. 

PMID- 25388198
TI  - Technological incorporation in the Unified Health System (SUS): the problem and
      ensuing challenges.
AB  - Technological incorporation is a central topic among the concerns regarding
      health care systems. This paper discusses the role of technology dynamics in
      health systems' cost increases, suggesting two different approaches - a
      'pragmatic-economic' approach and a 'rational-defensive' approach - as guidelines
      to explain the reasons for this centrality. The paper shows how judicialization
      results from this situation and discusses two doctrinal views - 'reserve for
      contingencies' and 'rational use' - as the views that usually guide the debates
      in the courts and among health policy makers. The paper suggests that the
      attitude currently prevalent in the Brazilian judiciary system can prejudice the
      principle of equity by improperly evaluating the principle of integrality. We
      present a brief genealogy of HTA and a timeline of HTA in Brazil. We also discuss
      the relevance and the impact of Law 12401/2011, which regulates the principle of
      integrality in the Unified Health System (SUS) and propose three challenges to
      the development of HTA actions aiming at technology incorporation in Brazil.
      Finally, we discuss the entry and the role of private health insurance companies,
      emphasizing changes in the scenario and in their position. 

PMID- 25388199
TI  - The use of medication and associated factors among adults living in Campinas, Sao
      Paulo, Brazil: differences between men and women.
AB  - The objective of this study was to verify factors associated with the use of
      medication by adults, with emphasis on the differences between men and women. It
      was a population-based, cross-sectional study with cluster sampling conducted in
      two stages in Campinas in the state of Sao Paulo in 2008. Among the 2,413
      individuals aged 20 or older, the prevalence of use of at least one drug in the
      three days before the research was 45.4% (95% CI: 41.3 - 49.4) in men and 64.6%
      (95% CI: 59.8 - 69.2) in women. For adult men over 40 years old who were not
      working, former smokers, with one or more chronic diseases, with two or more
      health problems and who sought health care or a health professional in the two
      weeks preceding the research showed higher prevalence of medication use. Among
      women, a higher prevalence of use was observed in females over 40, obese, former
      smokers, who reported a short sleep pattern, with one or more chronic diseases
      and two or more health problems, and who reported seeking a health care service
      or professional in the past 15 days. The findings showed some differences in the
      determinants of drug use in relation to gender, revealing the greater importance
      of health-related behavior among women. 

PMID- 25388202
TI  - Rational therapy publication rate correlates with wealth of a society.

PMID- 25388204
TI  - An integrated imaging probe design: the synthesis of (99m)Tc/Re-containing
      macrocyclic peptide scaffolds.
AB  - beta-Sheets account for over 30 % of all secondary structural conformations found
      in proteins. The intramolecular hydrogen bonding that exists between the two
      peptide strands is imperative in maintaining this secondary structure. With the
      proper design, cyclic peptides may act as scaffolds emulating active beta-sheet
      regions, enabling investigation of their importance in molecular recognition and
      protein aggregation. Starting from Fmoc-Lys(Fmoc)-OH, macrocyclic peptides were
      synthesized on a solid support, with peptide-chain elongation extending from both
      the alpha and epsilon amines of the lysine. The branching peptides were cyclized
      with a pyridyl tridentate chelation core followed by coordination using [(99m)
      Tc/Re(CO)3 (H2 O)3 ](+) . Variable temperature (1) H NMR spectroscopy studies
      were performed, demonstrating that intramolecular hydrogen bonding exists between
      the two sides of the uncoordinated macrocyclic peptide scaffolds. Additionally,
      computational modelling and circular dichroism spectroscopic analysis revealed
      that the peptide backbone exists in a similar conformation both before and after
      metal coordination. The ability to seamlessly incorporate a tridentate chelation
      core into the backbone of a macrocyclic peptide, without disrupting the secondary
      structure, can greatly assist in the design of metal-centric peptidomimetic
      imaging agents. This novel integrated imaging probe approach may facilitate the
      investigation into protein-protein interactions using macrocyclic beta-sheet
      scaffolds. 

PMID- 25388205
TI  - Case of palmoplantar pustulosis that developed with acute glomerulonephritis.

PMID- 25388206
TI  - Novel histone deacetylase inhibitors for the treatment of pediatric brain tumors.
AB  - Pediatric brain tumors (BT) represent a broad group of malignancies that affect
      children, displaying different degrees of aggressiveness and prognosis. Current
      studies demonstrate a crosslink between genetic and epigenetic changes within
      these tumors. Histone modifications are key elements in the pathogenesis of
      cancer in general and in brain tumors in particular. It is well documented that
      at least two classes of enzymes control acetylation of histones: histone
      acetyltransferases (HATs) and histone deacetylase (HDACs). Transformed HAT or
      HDAC action was identified in a number of human tumors. It has been hypothesized
      that HDACs regulate gene expression by deacetylating important genes for cell
      maintenance. Several HDACs inhibitors have been characterized in the last years
      and have been shown to promote growth blockage, differentiation and apoptosis in
      various types of tumors, including glioblastomas, medulloblastomas,
      neuroblastomas, melanomas, and leukemias. Some of these inhibitors are currently
      under clinical investigation for different cancer treatments. This review
      summarizes important mechanisms of histone modifications and discusses recent
      discoveries with impact on the pre-clinical and clinical field of pediatric brain
      tumor treatment.

PMID- 25388207
TI  - PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with
      implications to neuropathology.
AB  - Retinoids are morphogens and have been implicated in cell fate commitment of
      embryonic stem cells (ESCs) to neurons. Their effects are mediated by RAR and RXR
      nuclear receptors. However, transcriptional cofactors required for cell and gene
      specific retinoid signaling are not known. Here we show that protein arginine
      methyl transferase (PRMT) 1 and 8 have key roles in determining retinoid
      regulated gene expression and cellular specification in a multistage neuronal
      differentiation model of murine ESCs. PRMT1 acts as a selective modulator,
      providing the cells with a mechanism to reduce the potency of retinoid signals on
      regulatory "hotspots." PRMT8 is a retinoid receptor target gene itself and acts
      as a cell type specific transcriptional coactivator of retinoid signaling at
      later stages of differentiation. Lack of either of them leads to reduced nuclear
      arginine methylation, dysregulated neuronal gene expression, and altered neuronal
      activity. Importantly, depletion of PRMT8 results in altered expression of a
      distinct set of genes, including markers of gliomagenesis. PRMT8 is almost
      entirely absent in human glioblastoma tissues. We propose that PRMT1 and PRMT8
      serve as a rheostat of retinoid signaling to determine neuronal cell
      specification in a context-dependent manner and might also be relevant in the
      development of human brain malignancy.

PMID- 25388208
TI  - Integrin activation.
AB  - Integrin-mediated cell adhesion is important for development, immune responses,
      hemostasis and wound healing. Integrins also function as signal transducing
      receptors that can control intracellular pathways that regulate cell survival,
      proliferation, and cell fate. Conversely, cells can modulate the affinity of
      integrins for their ligands a process operationally defined as integrin
      activation. Analysis of activation of integrins has now provided a detailed
      molecular understanding of this unique form of "inside-out" signal transduction
      and revealed new paradigms of how transmembrane domains (TMD) can transmit long
      range allosteric changes in transmembrane proteins. Here, we will review how
      talin and mediates integrin activation and how the integrin TMD can transmit
      these inside out signals.

PMID- 25388209
TI  - Cellular and regional specific changes in multidrug efflux transporter expression
      during recovery of vasogenic edema in the rat hippocampus and piriform cortex.
AB  - In the present study, we investigated the characteristics of drug efflux
      transporter expressions following status epilepticus (SE). In the hippocampus and
      piriform cortex (PC), vasogenic edema peaked 3-4 days after SE. The expression of
      breast cancer resistance protein (BCRP), multidrug resistance protein-4 (MRP4),
      and p-glycoprotein (p-GP) were decreased 4 days after SE when vasogenic edema was
      peaked, but subsequently increased 4 weeks after SE. Multidrug resistance protein
      1 (MRP1) expression gradually decreased in endothelial cells until 4 weeks after
      SE. These findings indicate that SE-induced vasogenic edema formation transiently
      reduced drug efflux pump expressions in endothelial cells. Subsequently, during
      recovery of vasogenic edema drug efflux pump expressions were differentially
      upregulated in astrocytes, neuropils, and endothelial cells. Therefore, we
      suggest that vasogenic edema formation may be a risk factor in pharmacoresistent
      epilepsy.

PMID- 25388210
TI  - Role of histone deacetylase 2 and its posttranslational modifications in cardiac
      hypertrophy.
AB  - Cardiac hypertrophy is a form of global remodeling, although the initial step
      seems to be an adaptation to increased hemodynamic demands. The characteristics
      of cardiac hypertrophy include the functional reactivation of the arrested fetal
      gene program, where histone deacetylases (HDACs) are closely linked in the
      development of the process. To date, mammalian HDACs are divided into four
      classes: I, II, III, and IV. By structural similarities, class II HDACs are then
      subdivided into IIa and IIb. Among class I and II HDACs, HDAC2, 4, 5, and 9 have
      been reported to be involved in hypertrophic responses; HDAC4, 5, and 9 are
      negative regulators, whereas HDAC2 is a pro-hypertrophic mediator. The molecular
      function and regulation of class IIa HDACs depend largely on the phosphorylation
      mediated cytosolic redistribution, whereas those of HDAC2 take place primarily in
      the nucleus. In response to stresses, posttranslational modification (PTM)
      processes, dynamic modifications after the translation of proteins, are involved
      in the regulation of the activities of those hypertrophy-related HDACs. In this
      article, we briefly review 1) the activation of HDAC2 in the development of
      cardiac hypertrophy and 2) the PTM of HDAC2 and its implications in the
      regulation of HDAC2 activity.

PMID- 25388211
TI  - The thermal plasticity of locomotor performance has diverged between northern and
      southern populations of the eastern newt (Notophthalmus viridescens).
AB  - Many temperate ectotherms undergo thermal acclimation to remain functional over a
      wide range of body temperatures, but few studies have investigated whether
      populations of a single species have evolved differences in the thermal
      plasticity of locomotor performance. Therefore, we asked whether the thermal
      plasticity of locomotor performance has diverged between northern and southern
      populations of eastern newts (Notophthalmus viridescens). We acclimated eastern
      newts from Florida and Maine to cold (6  degrees C) or warm (28  degrees C)
      conditions for 12 weeks. Following acclimation, we measured the burst speed of
      newts at 6, 11.5, 17, 22.5, 28, and 33.5  degrees C. We also measured the
      activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in skeletal
      muscle of newts. The newts from Maine were better able to acclimate to low
      temperature compared to newts from Florida. Regardless of acclimation, the
      thermal sensitivity of burst speed was higher in the Florida compared to the
      Maine population. In general, newts from Maine performed better at low
      temperatures, whereas newts from Florida performed better at high temperatures.
      The activities of CK and LDH were lower in cold compared to warm-acclimated newts
      in the Florida population, but acclimation did not affect the activities of these
      enzymes in the Maine population. The activities of CK and LDH do not explain
      differences in the thermal plasticity of locomotor performance between
      populations. Our results demonstrate that the thermal sensitivity and plasticity
      of locomotor performance differ between northern and southern populations of
      eastern newts, suggesting that these traits readily adapt to the thermal
      environment.

PMID- 25388212
TI  - Breeding objectives for pigs in Kenya. I: bio-economic model development and
      application to smallholder production systems.
AB  - A deterministic bio-economic model was developed and applied to evaluate
      biological and economic variables that characterize smallholder pig production
      systems in Kenya. Two pig production systems were considered namely, semi
      intensive (SI) and extensive (EX). The input variables were categorized into
      biological variables including production and functional traits, nutritional
      variables, management variables and economic variables. The model factored the
      various sow physiological systems including gestation, farrowing, lactation,
      growth and development. The model was developed to evaluate a farrow to finish
      operation, but the results were customized to account for a farrow to weaner
      operation for a comparative analysis. The operations were defined as semi
      intensive farrow to finish (SIFF), semi-intensive farrow to weaner (SIFW),
      extensive farrow to finish (EXFF) and extensive farrow to weaner (EXFW). In SI,
      the profits were the highest at KES. 74,268.20 per sow per year for SIFF against
      KES. 4026.12 for SIFW. The corresponding profits for EX were KES. 925.25 and KES.
      626.73. Feed costs contributed the major part of the total costs accounting for
      67.0, 50.7, 60.5 and 44.5 % in the SIFF, SIFW, EXFF and EXFW operations,
      respectively. The bio-economic model developed could be extended with
      modifications for use in deriving economic values for breeding goal traits for
      pigs under smallholder production systems in other parts of the tropics. 

PMID- 25388213
TI  - Shape-engineering of self-assembled organic single microcrystal as optical
      microresonator for laser applications.
AB  - Single micro/nanocrystals based on pi-conjugated organic molecules have caused
      tremendous interests in the optoelectronic applications in laser, optical
      waveguide, nonlinear optics, and field effect transistors. However, the
      controlled synthesis of these organic micro/nanocrystals with regular shapes is
      very difficult to achieve, because the weak interaction (van der Waals' force,
      ca. 5 kJ/mol) between organic molecules could not dominate the kinetic process of
      crystal growth. Herein, we develop an elaborate strategy, selective adhesion to
      organic crystal plane by the hydrogen-bonding interaction (ca. 40 kJ/mol), for
      modulating the kinetic process of the formation of microcrystal, which leads to
      the self-assembly of one organic molecule 3-[4-(dimethylamino)phenyl]-1-(2-hy
      droxyphenyl)prop-2-en-1-on (HDMAC) into one-dimensional (1D) microwires and 2D
      microdisks respectively. Furthermore, these as-prepared microcrystals demonstrate
      shape-dependent microresonator properties that 1D microwires act as Fabry-Perot
      (FP) mode lasing resonator and 2D microdisks provide the whispering-gallery-mode
      (WGM) resonator for lasing oscillator. More significantly, through the
      investigation of the size-effect on the laser performance, single-mode lasing at
      red wavelength was successfully achieved in the self-assembled 2D organic
      microdisk at room temperature. These easily fabricated organic single-crystalline
      microcrystals with controlled shapes are the natural laser sources, which offer
      considerable promise for the multi-functionalities of coherent light devices
      integrated on the optics microchip.

PMID- 25388214
TI  - Re-profiling today's health care curricula for tomorrow's workforce: Establishing
      an interprofessional degree in Germany.
AB  - Laws regulating education of most health professional groups in Germany today
      mean that curricula re-profiling in response to changing priorities in the
      practice environment is a significant challenge. Legally dictated theoretical and
      clinical requirements for the vocational training of health professionals leaves
      little room for re-profiling in response to movements such as interprofessional
      education. An educational innovation was needed that worked within existing
      structures in Germany. The result was a formal collaboration between the Academy
      for Health Professionals and the University of Heidelberg allowing students
      undertaking vocational training to also complete a university degree in parallel.
      The aim of this article is to describe the curriculum development for the
      Bachelor of Science - Interprofessional Health Care. This article outlines an
      evidence-based approach to the process to curriculum development that resulted in
      a competency-based degree offering comprehensive interprofessional education at
      undergraduate level for healthcare students based in Germany. 

PMID- 25388216
TI  - Vacancy mobility and interaction with transition metal solutes in Ni.
AB  - Interaction of Re, Ta, W and Mo solutes with vacancies and their diffusion in fcc
      Ni is investigated by density-functional theory in combination with kinetic Monte
      Carlo simulations. Interaction energies are calculated for the first six neighbor
      shells around the solutes and a complete set of diffusion barriers for these
      shells is provided. Further, diffusion coefficients for the four elements in Ni
      as well as for vacancies in the presence of these elements are calculated. The
      calculated solute diffusion coefficients based on our ab initio data are found to
      compare favorably to experimental values. The mobility of the vacancies as a key
      factor in dislocation climb is only minimally influenced by the solute atoms
      within the dilute limit.

PMID- 25388217
TI  - Electron small polarons and their transport in bismuth vanadate: a first
      principles study.
AB  - Relatively low electron mobility has been thought to be a key factor that limits
      the overall photocatalytic performance of BiVO4, but the behavior of electrons
      has not been fully elucidated. We examine electron localization and transport in
      BiVO4 using hybrid density functional theory calculations. An excess electron is
      found to remain largely localized on one V atom. The predicted hopping barrier
      for the small polaron is 0.35 eV (with inclusion of 15% Hartree-Fock exchange),
      and tends to increase almost linearly with lattice constant associated with
      pressure and/or temperature changes. We also examine the interaction between
      polarons, and discuss the possible concentration-dependence of electron mobility
      in BiVO4. 

PMID- 25388215
TI  - Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma.
AB  - Epigenetic influences, such as DNA methylation, histone acetylation, and up
      regulation/down-regulation of genes by microRNAs, change the genetic makeup of an
      individual without affecting DNA base-pair sequences. Indeed, epigenetic changes
      play an integral role in the progression from normal esophageal mucosa to
      Barrett's esophagus to esophageal adenocarcinoma via dysplasia-metaplasia
      neoplasia sequence. Many genes involved in esophageal adenocarcinoma display
      hypermethylation, leading to their down-regulation. The classes of these genes
      include cell cycle control, DNA and growth factor repair, tumor suppressors,
      antimetastasis, Wnt-related genes, and proapoptotic genes. Histone acetylation in
      the pathophysiology of esophageal diseases has not been thoroughly investigated,
      and its critical role in the development of esophageal adenocarcinoma is less
      defined. Many microRNAs have been associated with the development of Barrett's
      esophagus and esophageal adenocarcinoma. Here, we critically addressed the
      specific steps most closely influenced by microRNAs in the progression from
      Barrett's esophagus to esophageal adenocarcinoma. However, microRNAs can target
      up to hundreds of genes, making it difficult to correlate directly with a given
      phenotype of the disease. Esophageal adenocarcinoma progressing from premalignant
      condition of Barrett's esophagus carries an extremely poor prognosis. Risk
      stratification for patients based on their epigenetic profiles may be useful in
      providing more targeted and directed treatment to patients. 

PMID- 25388218
TI  - Experimental and computational study of CO2 storage and sequestration with
      aqueous 2-amino-2-hydroxymethyl-1,3-propanediol (TRIS) solutions.
AB  - Experimental solubility data of CO2 in (5 and 10) mass% TRIS aqueous solutions
      were measured at (318.15 and 333.15) K and up to 10 MPa. The solubility data were
      well correlated with the modified Kent-Eisenberg model. The reaction mechanism,
      reaction energies, and equilibrium constants for the formation of bicarbonate and
      carbamate from CO2, H2O, and TRIS were studied using the quantum-chemical
      approach COSMO-RS (conductor-like screening model for real solvents) at the
      BP/TZVP level. The bicarbonate and carbamate formations were confirmed by using
      Fourier transform infrared (FTIR) spectroscopy. The results demonstrate that the
      formation of the bicarbonate anion is the main product formed by the direct
      reaction of CO2 with water and TRIS, and reveal that the carbamate anion was
      formed by a proton transfer from TRIS-CO2 zwitterion to TRIS. Density functional
      theory (DFT) calculations with transition-state optimization and intrinsic
      reaction coordinate (IRC) in water using IEF-PCM solvation model at the B3LYP/6
      311++G(d,p) levels of theory were employed to support the reaction pathway for
      the bicarbonate and carbamate formations. The conversion of the absorption
      product to stable carbonate (CaCO3) was also investigated experimentally by
      adding various Ca(2+) sources, CaCl2.2H2O aqueous solution, and artificial
      seawater. 

PMID- 25388219
TI  - Does use of pooled cohort risk score overestimate the use of statin?: a
      retrospective cohort study in a primary care setting.
AB  - BACKGROUND: Initiation of statin therapy as primary prevention particularly in
      those with mildly elevated cardiovascular disease risk factors is still being
      debated. The 2013 ACC/AHA blood cholesterol guideline recommends initiation of
      statin by estimating the 10-year atherosclerotic cardiovascular disease (ASCVD)
      risk using the new pooled cohort risk score. This paper examines the use of the
      pooled cohort risk score and compares it to actual use of statins in daily
      clinical practice in a primary care setting. METHODS: We examined the use of
      statins in a randomly selected sample of patients in a primary care clinic. The
      demographic data and cardiovascular risk parameters were captured from patient
      records in 1998. The pooled cohort risk score was calculated based on the
      parameters in 1998. The use of statins in 1998 and 2007, a 10-year interval, was
      recorded. RESULTS: A total of 847 patients were entered into the analysis. Mean
      age of the patients was 57.2 +/- 8.4 years and 33.1% were male. The use of
      statins in 1998 was only 10.2% (n = 86) as compared to 67.5% (n = 572) in 2007.
      For patients with LDL 70-189 mg/dl and estimated 10-year ASCVD risk >=7.5% (n =
      190), 60% (n = 114) of patients were on statin therapy by 2007. There were 124
      patients in whom statin therapy was not recommended according to ACC/AHA
      guideline but were actually receiving statin therapy. CONCLUSIONS: An extra 40%
      of patients need to be treated with statin if the 2013 ACC/AHA blood cholesterol
      guideline is used. However the absolute number of patients who needed to be
      treated based on the ACC/AHA guideline is lower than the number of patients
      actually receiving it in a daily clinical practice. The pooled cohort risk score
      does not increase the absolute number of patients who are actually treated with
      statins. However these findings and the use of the pooled cohort risk score need
      to be validated further.

PMID- 25388220
TI  - Delayed infection in duodenal duplication cyst after endoscopic ultrasound.

PMID- 25388221
TI  - Transplant glomerulopathy: the view from the other side of the basement membrane.

PMID- 25388222
TI  - GM-CSF Promotes Macrophage Alternative Activation after Renal
      Ischemia/Reperfusion Injury.
AB  - After kidney ischemia/reperfusion (I/R) injury, monocytes home to the kidney and
      differentiate into activated macrophages. Whereas proinflammatory macrophages
      contribute to the initial kidney damage, an alternatively activated phenotype can
      promote normal renal repair. The microenvironment of the kidney during the repair
      phase mediates the transition of macrophage activation from a proinflammatory to
      a reparative phenotype. In this study, we show that macrophages isolated from
      murine kidneys during the tubular repair phase after I/R exhibit an alternative
      activation gene profile that differs from the canonical alternative activation
      induced by IL-4-stimulated STAT6 signaling. This unique activation profile can be
      reproduced in vitro by stimulation of bone marrow-derived macrophages with
      conditioned media from serum-starved mouse proximal tubule cells. Secreted
      tubular factors were found to activate macrophage STAT3 and STAT5 but not STAT6,
      leading to induction of the unique alternative activation pattern. Using STAT3
      deficient bone marrow-derived macrophages and pharmacologic inhibition of STAT5,
      we found that tubular cell-mediated macrophage alternative activation is
      regulated by STAT5 activation. Both in vitro and after renal I/R, tubular cells
      expressed GM-CSF, a known STAT5 activator, and this pathway was required for in
      vitro alternative activation of macrophages by tubular cells. Furthermore,
      administration of a neutralizing antibody against GM-CSF after renal I/R
      attenuated kidney macrophage alternative activation and suppressed tubular
      proliferation. Taken together, these data show that tubular cells can instruct
      macrophage activation by secreting GM-CSF, leading to a unique macrophage
      reparative phenotype that supports tubular proliferation after sterile ischemic
      injury. 

PMID- 25388223
TI  - The two kidney to one kidney transition and transplant glomerulopathy: a podocyte
      perspective.
AB  - The attrition rate of functioning allografts beyond the first year has not
      improved despite improved immunosuppression, suggesting that nonimmune mechanisms
      could be involved. Notably, glomerulopathies may account for about 40% of failed
      kidney allografts beyond the first year of engraftment, and glomerulosclerosis
      and progression to ESRD are caused by podocyte depletion. Model systems
      demonstrate that nephrectomy can precipitate hypertrophic podocyte stress that
      triggers progressive podocyte depletion leading to ESRD, and that this process is
      accompanied by accelerated podocyte detachment that can be measured in urine.
      Here, we show that kidney transplantation "reverse nephrectomy" is also
      associated with podocyte hypertrophy and increased podocyte detachment. Patients
      with stable normal allograft function and no proteinuria had levels of podocyte
      detachment similar to levels in two-kidney controls as measured by urine podocyte
      assay. By contrast, patients who developed transplant glomerulopathy had 10- to
      20-fold increased levels of podocyte detachment. Morphometric studies showed that
      a subset of these patients developed reduced glomerular podocyte density within 2
      years of transplantation due to reduced podocyte number per glomerulus. A second
      subset developed glomerulopathy by an average of 10 years after transplantation
      due to reduced glomerular podocyte number and glomerular tuft enlargement.
      Reduced podocyte density was associated with reduced eGFR, glomerulosclerosis,
      and proteinuria. These data are compatible with the hypothesis that podocyte
      depletion contributes to allograft failure and reduced allograft half-life.
      Mechanisms may include immune-driven processes affecting the podocyte or other
      cells and/or hypertrophy-induced podocyte stress causing accelerated podocyte
      detachment, which would be amenable to nonimmune therapeutic targeting. 

PMID- 25388224
TI  - Vestibular functions were found to be impaired in patients with moderate-to
      severe obstructive sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: Obstructive sleep apnea (OSA) and balance disorders are
      common chronic diseases seen in the general population. The aim of this study was
      to evaluate vestibular functions in individuals with OSA. STUDY DESIGN: Cross
      sectional clinical study. METHODS: Patients who were referred to the sleep clinic
      in our hospital were classified into two groups according to a polysomnographic
      test: a moderate-to-severe OSA group and a mild OSA group. A vestibular system
      assessment of all patients was performed subjectively with the Dizziness Handicap
      Inventory (DHI) survey and objectively with videonystagmography. RESULTS: The
      current investigation produced four major findings: 1) Apnea-hypopnea index was
      significantly correlated with age and body mass index, whereas it was not
      correlated with Epworth Sleepiness Scale scores. 2) There was a significant
      difference in study groups in terms DHI scores, particularly in the physical
      subgroup. Moderate-to-severe OSA patients had higher scores in the physical
      subgroup of DHI. 3) Nystagmus and canal paresis rates were significantly higher
      in the moderate-to-severe OSA group when compared to the mild OSA group. 4)
      Results of the Romberg test, tandem Romberg test, cerebellar examinations, and
      positional tests were normal in both. CONCLUSIONS: Abnormal vestibular responses
      are common in individuals suffering from severe OSA, and dizziness has negative
      effects on the quality of life in these individuals. LEVEL OF EVIDENCE: 4

PMID- 25388226
TI  - Animal models of herpes simplex virus immunity and pathogenesis.
AB  - Herpes simplex viruses are ubiquitous human pathogens represented by two distinct
      serotypes: herpes simplex virus (HSV) type 1 (HSV-1); and HSV type 2 (HSV-2). In
      the general population, adult seropositivity rates approach 90% for HSV-1 and 20
      25% for HSV-2. These viruses cause significant morbidity, primarily as mucosal
      membrane lesions in the form of facial cold sores and genital ulcers, with much
      less common but more severe manifestations causing death from encephalitis. HSV
      infections in humans are difficult to study in many cases because many primary
      infections are asymptomatic. Moreover, the neurotropic properties of HSV make it
      much more difficult to study the immune mechanisms controlling reactivation of
      latent infection within the corresponding sensory ganglia and crossover into the
      central nervous system of infected humans. This is because samples from the
      nervous system can only be routinely obtained at the time of autopsy. Thus,
      animal models have been developed whose use has led to a better understanding of
      multiple aspects of HSV biology, molecular biology, pathogenesis, disease, and
      immunity. The course of HSV infection in a spectrum of animal models depends on
      important experimental parameters including animal species, age, and genotype;
      route of infection; and viral serotype, strain, and dose. This review summarizes
      the animal models most commonly used to study HSV pathogenesis and its
      establishment, maintenance, and reactivation from latency. It focuses
      particularly on the immune response to HSV during acute primary infection and the
      initial invasion of the ganglion with comparisons to the events governing
      maintenance of viral latency.

PMID- 25388225
TI  - No association between Apoepsilon4 alleles, HIV infection, age,
      neuropsychological outcome, or death.
AB  - The epsilon4 allele of the apolipoprotein E (ApoE) gene may have important
      interactions with physical health and cognitive function among individuals with
      HIV disease. The purpose of this study is to examine the relationships between
      epsilon4, HIV disease, age, neuropsychological impairment, and death in a large,
      well-characterized study sample. A total of 2846 men participating in the
      Multicenter AIDS Cohort Study had ApoE genotyping and neuropsychological test
      data available for analysis. We found a significant association between HIV
      infection and time to death (from any cause), as well as older age, race, and
      education. But, ApoE status was not significantly associated with time to death.
      Similarly, we found a significant association between HIV infection and time to
      incident cognitive impairment, as well as age, education, and HIV serostatus;
      Apoepsilon4 status was not related to incident cognitive impairment. There were
      no significant interactions between ApoE, HIV infection, and age on cognitive
      impairment. These data replicate and strengthen prior findings of the lack of
      association between ApoE epsilon4 and cognitive outcomes in HIV disease. We
      conclude that within the specific constraints of an exclusively male study in
      which the majority of participants were less than 65 years of age (range 22-87
      years), it appears reasonable to conclude that the epsilon4 allele is not
      significantly interacting with HIV serostatus. 

PMID- 25388227
TI  - Human papillomavirus type 197 is commonly present in skin tumors.
AB  - Non-melanoma skin cancers commonly contain Human Papillomavirus (HPV), but the
      types found have varied depending on the polymerase chain reaction (PCR) primer
      systems used. Whole genome amplified DNA (not amplified by any specific PCR
      primers) from 91 skin lesions [41 squamous cell skin carcinomas (SCCs), 8
      keratoacanthomas, 22 actinic keratoses, 3 basal cell carcinomas and 17 SCCs in
      situ] were sequenced. All samples were sequenced both at 160 Mb and 1.8 Gb
      sequencing depth per sample. The sequences from 10 different HPVs in 47/91
      specimens were found. Sequences represented four established HPV types (HPV types
      16, 22, 120, 124), two previously known putative types (present in GenBank) and
      four previously unknown HPV sequences (new putative types). The most commonly
      detected virus was cloned, sequenced and designated as HPV197. Type-specific real
      time PCR detected HPV197 in 34/91 specimens. For comparison, a pool of the same
      samples after general primer PCR amplification was also sequenced. This revealed
      40 different HPVs, but only two HPV types were detected both with sequencing
      without prior PCR and with sequencing PCR amplicons, suggesting that sequencing
      without prior PCR gives a more unbiased representation of the HPVs present. In
      summary, it was found that HPV can be sequenced from most skin disease specimens
      and HPV197 appeared to be the most commonly present virus. 

PMID- 25388228
TI  - Microbial community in anoxic-oxic-settling-anaerobic sludge reduction process
      revealed by 454 pyrosequencing analysis.
AB  - Modification of the anoxic-oxic (AO) process by inserting a sludge holding tank
      (SHT) into the sludge return line forms an anoxic-oxic-settling-anaerobic (A+OSA)
      process that can achieve a 48.98% sludge reduction rate. The 454 pyrosequencing
      method was used to obtain the microbial communities of the AO and A+OSA
      processes. Results showed that the microbial community structures of the 2
      processes were different as a result of the SHT insertion. Bacteria assigned to
      the phyla Proteobacteria and Bacteroidetes commonly existed and dominated the
      microbial populations of the 2 processes. However, the relative abundance of
      these populations shifted in the presence of SHT. The relative abundance of
      Proteobacteria decreased during the A+OSA process. A specific comparison at the
      class level showed that Sphingobacteria was enriched in the A+OSA process. The
      result suggested that the fermentative bacteria Sphingobacteria may have key
      functions in reducing the sludge from the A+OSA process. Uncultured
      Nitrosomonadaceae gradually became the dominant ammonia-oxidizing bacteria, and
      the nitrite-oxidizing bacterium Nitrospira was enriched in the A+OSA process.
      Both occurrences were favorable for stabilized nitrogen removal. The known
      denitrifying species in the A+OSA process were similar to those in the AO
      process; however, their relative abundance also decreased.

PMID- 25388229
TI  - Comparative perspectives on human gender development and evolution.
AB  - Human behavioral sex differences are ubiquitous, but the degree to which these
      sex differences are evolved or culturally invented is hotly contested across
      disciplines. A review of the human research yields strong evidence that somatic
      and social causes are both important in human behavioral sex differentiation, but
      researchers in this area struggle to agree on the relative importance of each.
      Understanding the social and somatic determinants of nonhuman primate sex-typed
      development may shed light on the relative responsibility of social and somatic
      causes of human behavioral sex differentiation. A review of this research (and
      related research on the proximate drivers of nonhuman primate behavioral
      development more generally) indicates that primate behavioral sex differentiation
      is rooted in somatic causes, but that these are situated in and cannot be
      extricated from social influences. Overt gender socialization and phenomena such
      as gender performance seem to be uniquely human. Primate research using a dynamic
      systems theoretical approach to behavioral development has the greatest potential
      to further clarify the workings of human behavioral sex differentiation, and
      further primate research is indispensable for understanding the evolution of
      human sex-typed behavior.

PMID- 25388230
TI  - Role of virtual bronchoscopy in children with a vegetable foreign body in the
      tracheobronchial tree.
AB  - OBJECTIVES: Multidetector computed tomography virtual bronchoscopy is a non
      invasive diagnostic tool which provides a three-dimensional view of the
      tracheobronchial airway. This study aimed to evaluate the usefulness of virtual
      bronchoscopy in cases of vegetable foreign body aspiration in children. METHODS:
      The medical records of patients with a history of foreign body aspiration from
      August 2006 to August 2010 were reviewed. Data were collected regarding their
      clinical presentation and chest X-ray, virtual bronchoscopy and rigid
      bronchoscopy findings. Cases of metallic and other non-vegetable foreign bodies
      were excluded from the analysis. Patients with multidetector computed tomography
      virtual bronchoscopy showing features of vegetable foreign body were included in
      the analysis. For each patient, virtual bronchoscopy findings were reviewed and
      compared with those of rigid bronchoscopy. RESULTS: A total of 60 patients; all
      children ranging from 1 month to 8 years of age, were included. The mean age at
      presentation was 2.01 years. Rigid bronchoscopy confirmed the results of
      multidetector computed tomography virtual bronchoscopy (i.e. presence of foreign
      body, site of lodgement, and size and shape) in 59 patients. In the remaining
      case, a vegetable foreign body identified by virtual bronchoscopy was revealed by
      rigid bronchoscopy to be a thick mucus plug. Thus, the positive predictive value
      of virtual bronchoscopy was 98.3 per cent. CONCLUSION: Multidetector computed
      tomography virtual bronchoscopy is a sensitive and specific diagnostic tool for
      identifying radiolucent vegetable foreign bodies in the tracheobronchial tree. It
      can also provide a useful pre-operative road map for rigid bronchoscopy. Patients
      suspected of having an airway foreign body or chronic unexplained respiratory
      symptoms should undergo multidetector computed tomography virtual bronchoscopy to
      rule out a vegetable foreign body in the tracheobronchial tree and avoid general
      anaesthesia and invasive rigid bronchoscopy.

PMID- 25388231
TI  - Graphical qualities of educational technology: Using drag-and-drop and text-based
      programs for introductory computer science.
AB  - To determine appropriate computer science curricula, educators sought to better
      understand the different affordances of teaching with a visual programming
      language (Alice) or a text-based language (Jython). Although students often
      preferred one language, that language wasn't necessarily the one from which they
      learned the most.

PMID- 25388232
TI  - Using global illumination in volume visualization of rheumatoid arthritis CT
      data.
AB  - Proper lighting in rendering is essential for visualizing 3D objects, but most
      visualization software tools still employ simple lighting models. The advent of
      hardware-accelerated advanced lighting suggests that volume visualization can be
      truly usable for clinical work. Researchers studied how volume rendering
      incorporating global illumination impacted perception of bone surface features
      captured by x-ray computed-tomography scanners for clinical monitoring of
      rheumatoid arthritis patients. The results, evaluated by clinical researchers
      familiar with the disease and medical-image interpretation, indicate that
      interactive visualization with global illumination helped the researchers derive
      more accurate interpretations of the image data. With clinical needs and the
      recent advancement of volume visualization technology, this study is timely and
      points the way for further research.

PMID- 25388233
TI  - Why integrate InfoVis and SciVis?: An example from systems biology.
AB  - The more-or-less artificial barrier between information visualization and
      scientific visualization hinders knowledge discovery. Having an integrated view
      of many aspects of the target data, including a seamlessly interwoven visual
      display of structural abstract data and 3D spatial information, could lead to new
      discoveries, insights, and scientific questions. Such a view also could reduce
      the user's cognitive load--that is, reduce the effort the user expends when
      comparing views. 

PMID- 25388234
TI  - Spatial user interfaces for large-scale projector-based augmented reality.
AB  - Spatial augmented reality applies the concepts of spatial user interfaces to
      large-scale, projector-based augmented reality. Such virtual environments have
      interesting characteristics. They deal with large physical objects, the
      projection surfaces are nonplanar, the physical objects provide natural passive
      haptic feedback, and the systems naturally support collaboration between users.
      The article describes how these features affect the design of spatial user
      interfaces for these environments and explores promising research directions and
      application domains.

PMID- 25388235
TI  - Random per-element luminance modulation for improved visual tracking.
AB  - Using random per-element luminance modulation can increase the visual salience of
      details in a range of visualizations (2D, 3D, and ND scalar, vector, and tensor
      fields). Although random luminance has been used in specific designs, its wide
      applicability isn't reflected in visualizations, perhaps because it hasn't yet
      been presented as a cross-cutting technique. Adding random-luminance contrast can
      benefit both static and animated visualizations. The article presents perceptual
      reasons for this technique's effectiveness. This article has two accompanying
      videos, at http://youtu.be/TTaSFMvBgvg and http://youtu.be/Rx1oPMTpPA4, showing
      animations of cones moving through a weather simulation, with and without random
      luminance modulation. 

PMID- 25388236
TI  - Expression of cadherin 17 in well-differentiated neuroendocrine tumours.
AB  - AIMS: Cadherin 17 (CDH17) is expressed primarily in normal intestinal epithelium
      and digestive tract tumours, and has limited expression in other neoplasms. The
      aims of this study were to examine CDH17 expression in well-differentiated
      neuroendocrine tumours (WDNETs) from various primary sites, representing the
      foregut, midgut, and hindgut, and tumours metastasizing to the liver, and to
      correlate the differences between the expression of CDH17, CDX2, and thyroid
      transcription factor 1 (TTF1). METHODS AND RESULTS: We investigated CDH17
      immunohistochemical expression in 150 primary WDNETs from eight anatomical sites,
      including 68 from the foregut, 70 from the midgut, and 12 from the hindgut, and
      15 metastases. CDH17 immunoreactivity increased significantly from foregut to
      hindgut WDNETs (P < 0.0001). Pancreatic WDNETs expressed CDH17 at a significantly
      higher frequency than other foregut tumours. Within the midgut, appendiceal and
      small-intestinal WDNETs were more frequently positive for CDH17 than for CDX2.
      All hindgut WDNETs expressed CDH17, in contrast to CDX2 (positive in one rectal
      case). CDH17 expression in liver metastases was similar to that of the primary
      tumours. CONCLUSIONS: This study is the first to comprehensively examine CDH17
      expression in WDNETs from different sites. CDH17 is a sensitive marker for midgut
      WDNETs, and the CDH17+/CDX2-/TTF1- phenotype was found to be sensitive (92%) and
      specific (91%) for hindgut WDNETs.

PMID- 25388237
TI  - A glutamatergic reward input from the dorsal raphe to ventral tegmental area
      dopamine neurons.
AB  - Electrical stimulation of the dorsal raphe (DR) and ventral tegmental area (VTA)
      activates the fibres of the same reward pathway but the phenotype of this pathway
      and the direction of the reward-relevant fibres have not been determined. Here we
      report rewarding effects following activation of a DR-originating pathway
      consisting of vesicular glutamate transporter 3 (VGluT3) containing neurons that
      form asymmetric synapses onto VTA dopamine neurons that project to nucleus
      accumbens. Optogenetic VTA activation of this projection elicits AMPA-mediated
      synaptic excitatory currents in VTA mesoaccumbens dopaminergic neurons and causes
      dopamine release in nucleus accumbens. Activation also reinforces instrumental
      behaviour and establishes conditioned place preferences. These findings indicate
      that the DR-VGluT3 pathway to VTA utilizes glutamate as a neurotransmitter and is
      a substrate linking the DR-one of the most sensitive reward sites in the brain-
      to VTA dopaminergic neurons.

PMID- 25388238
TI  - Hypothesis: cell signalling influences age-related risk of colorectal cancer.
AB  - We propose that ageing is linked to colonic carcinogenesis through crosstalk
      between Wnt activity and signalling pathways related to ageing and senescence:
      progerin, klotho and mTOR. Mutations in the Wnt signalling pathway are
      responsible for the majority of colorectal cancers (CRCs); however,
      hyperactivation of Wnt signalling by butyrate, a breakdown product of dietary
      fibre, induces CRC cell apoptosis. This effect of butyrate may in part explain
      the protective action of fibre against CRC. Hutchinson-Gilford progeria syndrome
      is a premature ageing disorder caused by accumulation of the progerin protein;
      however, healthy individuals also produce progerin in the course of their normal
      ageing. Progerin activates expression of the Wnt inhibitors HES1 and TLE1. Thus,
      we hypothesize that with age, the increasing expression of progerin suppresses
      butyrate-mediated Wnt hyperactivation and apoptosis, leading to increased CRC
      risk. Wild-type klotho contributes to a significantly increased lifespan;
      however, Klotho gene variants differ significantly between newborns and elderly.
      Klotho inhibits basal Wnt signalling activity; thus, the protein may function as
      a tumour suppressor for CRC. However, similar to progerin, klotho variants
      associated with lifespan differences may repress butyrate-mediated Wnt
      hyperactivation, and thus increase the risk of CRC. Finally, mTOR signalling has
      also been linked to human ageing, and crosstalk between Wnt and mTOR signalling
      may influence colonic tumourigenesis. Understanding how progerin, klotho and mTOR
      link ageing with colonic neoplastic development may lead to novel preventive and
      therapeutic strategies against CRC associated with age. 

PMID- 25388239
TI  - Morphological features of naevoid melanoma: results of a multicentre study of the
      International Dermoscopy Society.
AB  - BACKGROUND: Naevoid melanoma (NeM), a rare variant of melanoma, can be difficult
      to detect as its clinical and histopathological morphology can simulate a naevus.
      OBJECTIVES: To describe the clinical and dermoscopic features associated with
      NeM. METHODS: Lesions with a histopathological diagnosis of NeM were collected
      via an e-mail request sent to all members of the International Dermoscopy
      Society. All lesions were histopathologically reviewed and only lesions
      fulfilling a set of predefined histopathological criteria were included in the
      study and analysed for their clinical and dermoscopic features. RESULTS: Twenty
      seven of 58 cases (47%) fulfilled the predefined histopathological criteria for
      NeM and were included in the study. Clinically, 16 of the 27 NeMs presented as a
      nodular lesion (59%), eight (30%) as plaque type and three (11%) as papular.
      Analysis of the global dermoscopic pattern identified three types of NeM. The
      first were naevus-like tumours (n = 13, 48%), typified by a papillomatous surface
      resembling a dermal naevus. In these lesions local dermoscopic features included
      irregular dots/globules (46%), multiple milia-like cysts (38%) and atypical
      vascular structures (46%). The second type were amelanotic tumours (n = 8, 30%),
      typified by an atypical vascular pattern (75%). The third type consisted of
      tumours displaying a multicomponent pattern (n = 4, 15%), characterized by
      classical local melanoma-specific criteria. Two lesions (7%) were classified as
      mixed-pattern tumours as they did not manifest any of the aforementioned
      patterns. CONCLUSIONS: While NeMs may be clinically difficult to differentiate
      from naevi, any papillomatous lesion displaying dermoscopically atypical vessels
      and/or irregular dots/globules should prompt consideration for the possible
      diagnosis of NeM.

PMID- 25388240
TI  - Liraglutide for the treatment of type 2 diabetes mellitus: a meta-analysis of
      randomized placebo-controlled trials.
AB  - INTRODUCTION: Liraglutide has been widely used in the treatment of type 2
      diabetes mellitus (T2DM), however, the results of a number of randomized placebo
      controlled trials on the effects of liraglutide for the treatment of T2DM have
      varied. The purpose of this study was to assess the effects of liraglutide versus
      placebo for the treatment of T2DM. METHODS: We searched randomized controlled
      trials comparing liraglutide and placebo for the treatment of T2DM in the
      following databases: MEDLINE; EMBASE; Cochrane Library Central Register of
      Controlled Trials; and Clinical Trials Gov (through August 2014). The standard
      mean difference (SMD) was calculated for the continuous data and a chi (2) test
      was used to evaluate heterogeneity. RESULTS: Initially, 103 articles were
      retrieved through the literature search and 11 studies met the requirements for
      the meta-analysis. The effects of liraglutide on lowering glycosylated
      hemoglobin, fasting plasma glucose, reducing weight, lowering blood pressure, and
      the prevalence of adverse events were significantly different from placebo (P <
      0.0001, SMD = -0.96, 95% CI = [-1.20, -0.73]; P < 0.0001, SMD = -0.72, 95% CI = [
      0.99, -0.45]; P = 0.004, SMD = -0.24, 95% CI = [-0.40, -0.07]; P = 0.021, SMD = 
      0.15, 95% CI = [-0.27, -0.02], and P = 0.007, respectively). CONCLUSION:
      Liraglutide had greater hypoglycemic, weight-reducing and systolic blood pressure
      lowering effects than placebo. However, there were more adverse events in the
      treatment with liraglutide. It is suggested that additional well-designed, large,
      studies be conducted to further support the use of liraglutide and provide
      objective guidance for clinical application of liraglutide.

PMID- 25388241
TI  - Paul Ehrlich's mastzellen: a historical perspective of relevant developments in
      mast cell biology.
AB  - Following the discovery of mast cells (or mastzellen) by the prolific physician
      researcher, Paul Ehrlich, many advances have improved our understanding of these
      cells and their fascinating biology. The discovery of immunoglobulin E and
      receptors for IgE and IgG on mast cells heralded further in vivo and in vitro
      studies, using molecular technologies and gene knockout models. Mast cells
      express an array of inflammatory mediators including tryptase, histamine,
      cytokines, chemokines, and growth factors. They play a role in many varying
      disease states, from atopic diseases, parasitic infections, hematological
      malignancies, and arthritis to osteoporosis. This review will attempt to
      summarize salient evolving areas in mast cell research over the last few
      centuries that have led to our current understanding of this pivotal
      multifunctional cell. 

PMID- 25388242
TI  - The phylogenetic profile of mast cells.
AB  - Mast cells (MCs) are tissue-based immune cells that participate to both innate
      and adaptive immunities as well as to tissue-remodelling processes. Their
      evolutionary history appears as a fascinating process, whose outline we can only
      partly reconstruct according to current remnant evidence. MCs have been
      identified in all vertebrate classes, and a cell population with the overall
      characteristics of higher vertebrate MCs is identifiable even in the most
      evolutionarily advanced fish species. In invertebrates, cells related to
      vertebrate MCs have been recognized in ascidians, a class of urochordates which
      appeared approximately 500 million years ago. These comprise the granular
      hemocyte with intermediate characteristics of basophils and MCs and the "test
      cell" (see below). Both types of cells contain histamine and heparin, and provide
      defensive functions. The test cell releases tryptase after stimulation with
      compound 48/80. A leukocyte ancestor operating in the context of a primitive
      local innate immunity probably represents the MC phylogenetic progenitor. This
      cell was likely involved in phagocytic and killing activity against pathogens and
      operated as a general inducer of inflammation. This early type of defensive cell
      possibly expressed concomitant tissue-reparative functions. With the advent of
      recombinase activating gene (RAG)-mediated adaptive immunity in the Cambrian era,
      some 550 million years ago, and the emergence of early vertebrates, MC
      progenitors differentiated towards a more complex cellular entity. Early MCs
      probably appeared in the last common ancestor we shared with hagfish, lamprey,
      and sharks about 450-500 million years ago. 

PMID- 25388243
TI  - Mast cell development and function in the zebrafish.
AB  - The many advantages of the zebrafish model provide a unique opportunity to
      integrate the tools of developmental embryology, transgenesis, and functional
      assays to elucidate the molecular pathways underlying hematopoiesis and for
      modeling human blood diseases. These methodologies have recently been applied to
      the zebrafish mast cell lineage and have resulted in a better understanding of
      vertebrate mast cell biology. By employing whole-mount in situ hybridization
      alone and in combination with co-localization approaches, fluorescence-activated
      cell sorting (FACS), and morpholino gene knockdown studies, new insights into
      early mast cell transcriptional regulation and ontogeny have been exposed in
      vivo. Transgenic strategies have permitted the modeling of human mast cell
      diseases, like systemic mastocytosis in zebrafish, which can subsequently be
      exploited for high-throughput chemical screens to identify potential therapies in
      these conditions. Mast cell functional assays have been adapted to zebrafish
      providing the opportunity to utilize this model for interrogating the cellular
      players in innate and adaptive immunity and as a live animal readout for drug
      responses in allergic and inflammatory reactions. These techniques are detailed
      in the following chapter. 

PMID- 25388244
TI  - Human mast cell and basophil/eosinophil progenitors.
AB  - Mast cell, basophil, and eosinophil lineages all derive from CD34(+) hemopoietic
      stem cells; however, mast cells are derived from a distinct, nonmyeloid
      progenitor, while eosinophils and basophils share a common myeloid progenitor.
      These progenitors likely evolved from an ancestral leukocyte population involved
      in innate immunity and currently play a central role in the pathology of allergic
      disease. Advances in isolation and analysis of mast cell and basophil/eosinophil
      progenitor populations have been critical to understanding lineage commitment,
      differentiation, function, and transcriptional regulation of these cells and have
      provided a way of monitoring the effect of novel investigational therapies on
      these cell populations in samples of blood, bone marrow, and airway secretions. 

PMID- 25388245
TI  - Methods for the study of mast cell recruitment and accumulation in different
      tissues.
AB  - Mast cells (MC) are important effector cells involved in a wide range of
      inflammatory diseases. The lineage-committed, tissue-localized progenitor (MCp)
      is not easily identified histochemically like the mature MC because they lack the
      distinctive cytoplasmic granules. However, they can be identified by their unique
      cell surface phenotype and by their ability to be expanded in culture using
      selective growth factors. Here we describe the methods that allow evaluation of
      MCp and mature MC in peripheral tissues under basal and inflammatory conditions.
      Thus, one can enumerate mature MC as well as immature committed progenitors in
      order to study basal homing, inflammatory recruitment, maturation, and life span.
      We also provide an analysis of difficulties that could emerge during these
      procedures. 

PMID- 25388246
TI  - Notch2 signaling in mast cell development and distribution in the intestine.
AB  - Notch signaling controls cell-fate specification events in various types of blood
      cells, and it further regulates the function of particular blood cells. Recent
      studies have identified the role of Notch signaling as a determinant of mast cell
      fate from bone marrow progenitors and mast cell maturation towards mucosal type
      rather than connective tissue type. Furthermore, Notch2 has functional properties
      for immune defense against Strongyloides venezuelensis through properly
      distributing intestinal mast cells. The goal of this chapter is to provide the
      researchers with the comprehensive protocols to examine the functions of Notch
      signaling in mast cells both in vitro and in vivo. 

PMID- 25388247
TI  - Mast cells in human health and disease.
AB  - Mast cells are primarily known for their role in defense against pathogens,
      particularly bacteria; neutralization of venom toxins; and for triggering
      allergic responses and anaphylaxis. In addition to these direct effector
      functions, activated mast cells rapidly recruit other innate and adaptive immune
      cells and can participate in "tuning" the immune response. In this review we
      touch briefly on these important functions and then focus on some of the less
      appreciated roles of mast cells in human disease including cancer, autoimmune
      inflammation, organ transplant, and fibrosis. Although it is difficult to
      formally assign causal roles to mast cells in human disease, we offer a general
      review of data that correlate the presence and activation of mast cells with
      exacerbated inflammation and disease progression. Conversely, in some restricted
      contexts, mast cells may offer protective roles. For example, the presence of
      mast cells in some malignant or cardiovascular diseases is associated with
      favorable prognosis. In these cases, specific localization of mast cells within
      the tissue and whether they express chymase or tryptase (or both) are
      diagnostically important considerations. Finally, we review experimental animal
      models that imply a causal role for mast cells in disease and discuss important
      caveats and controversies of these findings. 

PMID- 25388249
TI  - The parasympathetic nervous system as a regulator of mast cell function.
AB  - Often considered as the archetype of neuroimmune communication, much of our
      understanding of the bidirectional relationship between the nervous and immune
      systems has come from the study of mast cell-nerve interaction. Mast cells play a
      role in resistance to infection and are extensively involved in inflammation and
      subsequent tissue repair. Thus, the relationship between mast cells and neurons
      enables the involvement of peripheral and central nervous systems in the
      regulation of host defense mechanisms and inflammation. Recently, with the
      identification of the cholinergic anti-inflammatory pathway, there has been
      increased interest in the role of the parasympathetic nervous system in
      regulating immune responses. Classical neurotransmitters and neuropeptides
      released from cholinergic and inhibitory NANC neurons can modulate mast cell
      activity, and there is good evidence for the existence of parasympathetic nerve
      mast cell functional units in the skin, lung, and intestine that have the
      potential to regulate a range of physiological processes.

PMID- 25388248
TI  - The emerging prominence of the cardiac mast cell as a potent mediator of adverse
      myocardial remodeling.
AB  - Cardiac mast cells store and release a variety of biologically active mediators,
      several of which have been implicated in the activation of matrix
      metalloproteinases in the volume-overloaded heart, while others are involved in
      the fibrotic process in pressure-overloaded hearts. Increased numbers of mast
      cells have been reported in explanted human hearts with dilated cardiomyopathy
      and in animal models of experimentally induced hypertension, myocardial
      infarction, and chronic cardiac volume overload. Also, there is evolving evidence
      implicating the cardiac mast cell as having a major role in the adverse
      remodeling underlying these cardiovascular disorders. Thus, the cardiac mast cell
      is the focus of this chapter that begins with a historical background, followed
      by sections on methods for their isolation and characterization, endogenous
      secretagogues, phenotype, and ability of estrogen to alter their phenotype so as
      to provide cardioprotection. Finally the role of mast cells in myocardial
      remodeling secondary to a sustained cardiac volume overload, hypertension, and
      ischemic injury and future research directions are discussed. 

PMID- 25388250
TI  - Growth of human mast cells from bone marrow and peripheral blood-derived CD34(+)
      pluripotent hematopoietic cells.
AB  - Human mast cells (HuMCs) are derived from CD34(+) pluripotent hematopoietic cells
      which are KIT (CD117)(+) and FcepsilonRI(-), and lack lineage-specific surface
      markers. Bone marrow and peripheral blood are the two readily available sources
      for obtaining CD34(+) cells from which HuMCs can be cultured. CD34(+) cells are
      isolated and enriched by magnetic separation columns and stored under specific
      conditions until ready for use. Alternatively, enriched CD34(+) cells may be
      immediately cultured in serum-free culture media containing recombinant human
      (rh) stem cell factor (SCF), rhIL-6, and rhIL-3 (added only during the first
      week). Weekly hemidepletions and removal of adherent cells and/or debris enables
      the investigator to obtain HuMC cultures, identified by Wright-Giemsa and acidic
      toluidine blue stains, by 8-10 weeks. 

PMID- 25388251
TI  - Isolation and characterization of human intestinal mast cells.
AB  - Mast cells are granulated immune cells typically located at barrier sites of the
      body, such as the skin and the mucosa of the respiratory, urogenital, and
      gastrointestinal tract. They are well known for their capacity to participate in
      the orchestration of inflammatory and immune responses by releasing a broad array
      of mediators as a consequence of IgE-dependent and IgE-independent activation.
      Mast cells derive from myeloid progenitors, but in contrast to other myeloid
      cells, they leave the bone marrow in an immature state; therefore, mast cells are
      not visible in the blood under normal conditions. For full maturation, the tissue
      environment is necessary. Thus, mature mast cells can be only isolated from
      tissue such as skin or mucosal sites, which makes mast cell isolation
      complicated. This chapter describes methods to isolate, purify, and culture mast
      cells from the human intestinal mucosa. Human mucosal mast cells can be used to
      characterize their mediators and to study the mechanisms of human mast cell
      activation, signal transduction, and exocytosis in response to specific stimuli. 

PMID- 25388252
TI  - Human mast cell activation with viruses and pathogen products.
AB  - Mast cells have been demonstrated to have critical roles in host defense against
      a number of types of pathogens. In order to better understand how mast cells
      participate in effective immune responses, it is important to evaluate their
      ability to respond directly to pathogens and their products. In the current
      chapter we provide a methodology to evaluate human mast cell responses to a
      number of bacterial and fungal pathogen products and to mammalian reovirus as a
      model of acute viral infection. These methods should provide key information
      necessary to aid in the effective design of experiments to evaluate human mast
      cell responses to a number of other organisms. However, it is important to
      carefully consider the biology of the mast cell subsets and pathogens involved
      and the optimal experimental conditions necessary to evaluate mediators of
      interest. 

PMID- 25388253
TI  - Basic techniques to study FcepsilonRI signaling in mast cells.
AB  - Mast cells are the crucial effector cells for allergic reactions. They are
      activated through the aggregation of the high-affinity IgE receptor (FcepsilonRI)
      with allergen and allergen-specific IgE. Tyrosine phosphorylation of FcepsilonRI
      subunits and various signaling proteins is an initial triggering event, leading
      to the activation of several signaling pathways in mast cells. Much has been
      learned from analysis of mast cells derived from gene-targeted mice. Therefore,
      in this chapter we will first describe how to generate mast cells from mouse bone
      marrow cells and how to correct the genetic defect by retroviral transduction.
      Then we will describe how to assess early activation events by measuring several
      protein-tyrosine kinases (PTKs) and serine/threonine kinases (PS/TKs) such as Akt
      (protein kinase B), protein kinase C (PKC), and JNK. As signal transduction is
      highly dependent on protein-protein interactions, we will describe experimental
      details of co-immunoprecipitation methods that are used to confirm such
      interactions. 

PMID- 25388254
TI  - Membrane-cytoskeleton dynamics in the course of mast cell activation.
AB  - Aggregation of the high-affinity IgE receptor (FcepsilonRI) on the plasma
      membrane of mast cells and basophils initiates signaling events leading to a
      rapid release of preformed inflammatory mediators from secretory granules, and
      overall changes in cell morphology. Mast cell activation also causes
      reorganization of cytoskeletal components associated with membrane ruffling,
      spreading, and migration. Here we describe methods used for visualization of mast
      cell cytoskeleton, focusing on its two major components, microfilaments and
      microtubules, and their changes after cell triggering. 

PMID- 25388255
TI  - FcepsilonRI expression and dynamics on mast cells.
AB  - Mast cells are key effector and immunoregulatory cells in IgE-associated immune
      responses, including allergic disorders. IgE antibodies bind to the high-affinity
      IgE receptor, FcepsilonRI, expressed on the surface of mast cells; antigen
      induced cross-linking of FcepsilonRI-bound IgE molecules activates the mast cell
      to release an array of proinflammatory and immunomodulatory mediators. Because
      mast cells often respond to very low levels of antigen in vivo, the level of
      FcepsilonRI expressed on the surface of these cells is an important factor in
      determining the responsiveness of these cells to antigen. FcepsilonRI surface
      expression is regulated by a number of processes, including FcepsilonRI
      stabilization, FcepsilonRI recycling, and antigen-induced internalization.
      Although members of the Rab family of small GTPases and the ubiquitin ligase,
      Cbl, have recently emerged as major regulators of many of the membrane
      trafficking events that govern FcepsilonRI expression levels, the mechanisms and
      intracellular pathways that regulate FcepsilonRI trafficking remain poorly
      defined. This chapter outlines a number of flow cytometry-based assays that can
      be used to investigate cell surface FcepsilonRI expression and dynamics
      (stabilization, recycling, and internalization) on bone marrow-derived mast cells
      (BMCMCs), the most commonly used model system for studying mast cells in vitro.
      Given the importance of FcepsilonRI levels to mast cell responsiveness and
      function, the characterization of FcepsilonRI expression and dynamics on
      different mast cell populations is critical when trying to compare IgE-dependent
      processes between different mast cell populations. 

PMID- 25388256
TI  - Regulation of mast cell survival and apoptosis.
AB  - One key characteristic of certain mast cell populations is their longevity. Mast
      cell survival can also be promoted by Fc-receptor activation. Regulation of cell
      survival and apoptosis is regulated by the Bcl-2 family that consists of pro- and
      anti-apoptotic proteins. Depending on their relative cellular expression levels,
      the cells are either rescued or destined for apoptosis. To determine the
      regulation of mast cell survival and apoptosis, the expression of different Bcl-2
      protein family members can be measured by western blot. The amount of viable
      versus apoptotic cells is decided by AnnexinV/propidium iodide staining, and cell
      lysates are prepared for western blot analysis from the appropriated time points.

PMID- 25388257
TI  - Protein tyrosine phosphatases in mast cell signaling.
AB  - For a time, mast cells were viewed as simple granulocytic effector cells that
      mediate allergic symptoms. More recent discoveries show that mast cells can also
      function as potent pro- and anti-inflammatory immune regulators in a plethora of
      human diseases. Much of the current knowledge about mast cell functions comes
      from studies on rodent models. The membrane receptors for antigen/IgE and growth
      factors are the core initiators of signaling cascades that trigger various mast
      cell responses. Yet, the regulation and multifunctionality of key receptor
      proximal protein tyrosine phosphorylation events are still not well understood.
      The roles of the members of the protein tyrosine phosphatase superfamily of
      enzymes in regulating mast cell development, survival, and immune activation will
      be reviewed in this chapter. 

PMID- 25388258
TI  - MicroRNA function in mast cell biology: protocols to characterize and modulate
      microRNA expression.
AB  - MicroRNAs (miRNAs) are small noncoding RNA molecules that can modulate mRNA
      levels through RNA-induced silencing complex (RISC)-mediated degradation.
      Recognition of target mRNAs occurs through imperfect base pairing between an
      miRNA and its target, meaning that each miRNA can target a number of different
      mRNAs to modulate gene expression. miRNAs have been proposed as novel therapeutic
      targets and many studies are aimed at characterizing miRNA expression patterns
      and functions within a range of cell types. To date, limited research has focused
      on the function of miRNAs specifically in mast cells; however, this is an
      emerging field. In this chapter, we will briefly overview miRNA synthesis and
      function and the current understanding of miRNAs in hematopoietic development and
      immune function, emphasizing studies related to mast cell biology. The chapter
      will conclude with fundamental techniques used in miRNA studies, including RNA
      isolation, real-time PCR and microarray approaches for quantification of miRNA
      expression levels, and antagomir design to interfere with miRNA function. 

PMID- 25388259
TI  - Assay of mast cell mediators.
AB  - Mediator release from activated mast cells is a major initiator of the
      symptomology associated with allergic disorders such as anaphylaxis and asthma.
      Thus, methods to monitor the generation and release of such mediators have
      widespread applicability in studies designed to understand the processes
      regulating mast cell activation and for the identification of therapeutic
      approaches to block mast cell-driven disease. In this chapter, we discuss
      approaches used for the determination of mast cell degranulation, lipid-derived
      inflammatory mediator production, and cytokine/chemokine gene expression as well
      as cytokine release. 

PMID- 25388260
TI  - Induction of mast cell apoptosis by a novel secretory granule-mediated pathway.
AB  - Mast cells (MCs) have detrimental functions in the context of numerous
      pathologies, and regimens aimed at neutralizing MCs or individual MC products can
      thus be of therapeutic value. One way to target MCs in disease is to selectively
      induce MC apoptosis, but there is so far no agent available that selectively
      induces apoptosis in MCs. Mast cells are heavily loaded with secretory granules
      containing large amounts of fully active proteases bound to serglycin
      proteoglycan. Damage to the secretory granules will thus lead to the release of
      serglycin-protease complexes into the cytosol. A potential consequence of this
      would be that the unleashed granular proteases cause apoptosis by proteolytic
      activation of proapoptotic compounds located in the cytosol. Indeed, we have
      recently found that MCs are highly sensitive to apoptosis induced by
      permeabilization of the secretory granules. In this chapter, we describe the
      methods used to study MC apoptosis induced by this novel, secretory granule
      mediated pathway. 

PMID- 25388261
TI  - Measurement of nitric oxide in mast cells with the fluorescent indicator DAF-FM
      diacetate.
AB  - The production of nitric oxide in mast cells has been difficult to measure due to
      the low amounts made by mast cells, as well as limitations in the specificity and
      sensitivity of the assays available. We present here a sensitive and specific 96
      well plate-based method to directly measure NO using the cell-permeable
      fluorescent compound DAF-FM diacetate. 

PMID- 25388262
TI  - Real-time imaging of Ca(2+) mobilization and degranulation in mast cells.
AB  - Mast cells play a key role in allergy and inflammation processes as part of the
      immune response. The activation of mast cells via antigen binding and cross
      linking of IgE receptors initiates the onset of dramatic calcium (Ca(2+))
      mobilization dynamics that promote the release of mediators of inflammation and
      allergy. Ca(2+) signaling in mast cells has been studied extensively using a
      variety of research tools and techniques. In these studies, a large number of
      proteins have been identified to participate in various stages of these
      processes. Here we describe single-cell imaging as an important approach for
      examining Ca(2+) signaling and exocytosis in mast cells. Single-cell imaging
      tools have advanced significantly over the last 10 years, in part due to
      improvements in microscope technology and in part due to the development of a new
      generation of Ca(2+) indicators and genetically encoded Ca(2+) sensors. The
      single-cell imaging techniques described here provide the spatial and temporal
      resolution required to decipher the signaling events that are critical for mast
      cell functions.

PMID- 25388263
TI  - Flow cytometry-based monitoring of mast cell activation.
AB  - Mast cell activation is a central process in the initiation of allergic
      disorders. As described elsewhere in this volume, this process can be readily
      monitored by biochemical, antibody-based, and enzyme-based formats when the cell
      population examined is homogenous. When dealing with mixed and transfected cell
      populations however, such approaches may not be appropriate. Hence alternative
      methods are required. Here we describe flow-cytometry-based assays that can be
      utilized to examine signaling processes and degranulation in both pure mast cell
      populations and, following appropriate selection, in populations where the mast
      cells of interest may only represent a fraction of the total cell population. 

PMID- 25388264
TI  - Measurement of mast cell surface molecules by high-throughput immunophenotyping
      using transcription (HIT).
AB  - Here we describe the application of a highly multiplexed proteomic assay, called
      HIT (high-throughput immunophenotyping using transcription), to analyze human
      mast cell surface antigens at rest and during stimulation. HIT allows analysis of
      up to 100 analytes, including surface antigens and intracellular phosphoproteins,
      transcription factors, and cytokines, in a single experiment. Briefly, anti-mouse
      monovalent Fab fragments are covalently conjugated with barcoded oligonucleotides
      to generate a panel of conjugates. The oligonucleotide-Fab fragment conjugates
      are bound to monoclonal primary antibodies, creating a cocktail of up to 48
      unique barcoded primary antibodies. As few as 100,000 mast cells are stained with
      the cocktail and the barcodes of the bound primary antibodies are amplified by in
      vitro transcription with fluorescently labeled NTPs. The resulting barcoded
      transcripts are quantified using a microarray spotted with oligonucleotides that
      are complementary to the barcoded transcripts. Differences in levels of the
      barcoded transcripts correlate well with actual protein levels and are capable of
      detecting stimulation-dependent changes in protein levels. HIT is an invaluable,
      broad-spectrum approach for characterizing mast cell surface antigens, signaling
      molecules, transcription factors, and cytokines. 

PMID- 25388265
TI  - Cre/loxP-based mouse models of mast cell deficiency and mast cell-specific gene
      inactivation.
AB  - Over the past decades, research on in vivo functions of mast cells has largely
      relied on kit-mutant mouse strains. Recently, new mouse models for investigation
      of mast cell functions based on the Cre/loxP recombination system have been
      published and results in these new models challenged findings of previous studies
      in kit-mutant mice. Herein we describe procedures central to mast cell-specific
      gene inactivation and the generation of mast cell-deficient mice based on the
      mouse strain Mcpt5-Cre, which expresses Cre recombinase selectively in connective
      tissue mast cells. 

PMID- 25388266
TI  - Evaluation of synovial mast cell functions in autoimmune arthritis.
AB  - Mast cells are innate immune effector cells that reside in the healthy synovial
      sublining and expand in number with inflammation. These cells can play an
      important role in initiation of arthritis, but much about their biology and
      importance remains obscure. This chapter reviews the use of animal models for the
      study of mast cells in arthritis, with a particular focus on the K/BxN serum
      transfer model. We discuss tissue preparation and histological analysis for the
      assessment of joint inflammation, injury, and the presence and phenotype of
      synovial mast cells, as well as the use of bone marrow-derived mast cell (BMMC)
      engraftment into W/Wv mice as a tool to isolate the role of mast cells in joint
      inflammation and injury. 

PMID- 25388267
TI  - Methods for the study of mast cells in cancer.
AB  - Tumor growth requires interactions of tumor cells with a receptive and inductive
      microenvironment. Two major populations of tumor-infiltrating cells are
      considered to be essential for producing such a microenvironment: (1)
      proinflammatory cells that nurture the tumor with growth factors and facilitate
      invasion and metastasis by secreting proteases and (2) immune suppressive
      leukocytes including T-regulatory cells (Treg) that hinder tumor-specific CD8 T
      cell responses, which otherwise could potentially reject the tumor. Among the
      proinflammatory cells, accumulation of mast cells (MCs) in human tumors is
      frequently recorded and was recently linked with poor prognosis. Causative links
      between mast cell infiltration and tumor progression can be deduced from animal
      studies. There is an interesting link between mast cells and Treg. The adoptive
      transfer of Treg from healthy syngeneic mice to mice susceptible to colon cancer
      suppresses focal mastocytosis and hinders tumor progression. Furthermore, T-cell
      deficient mice susceptible to colon cancer show enhanced focal mastocytosis and
      tumor invasion. Here, we describe methods to assess MCs in mouse models of cancer
      and to investigate how MCs affect tumor epithelium. Additionally, we will detail
      methods used to investigate how T cells influence MCs and how MCs influence T
      cells. 

PMID- 25388268
TI  - Studying mast cells in peripheral tolerance by using a skin transplantation
      model.
AB  - Mast cells (MCs) play an important role in both inflammatory and
      immunosuppressive responses [1]. The importance of MCs in maintaining peripheral
      tolerance was discovered in a FoxP3(+) regulatory T-cell (Treg)-mediated skin
      transplant model [2]. MCs can directly mediate tolerance by releasing anti
      inflammatory mediators (reviewed in ref. 3) or by interacting with other immune
      cells in the graft. Here we will present protocols used to study the role of MCs
      in peripheral tolerance with the emphasis on how MCs can regulate T-cell
      functionality. First we will introduce the skin transplant model followed by
      reconstitution of mast cell-deficient mice (B6.Cg-Kit (W-sh) ). This includes the
      preparation of MCs from the bone marrow. Finally the methods used to study the
      influence of MCs on T-cell responses and Treg functionality will be presented by
      modulating the balance between tolerance and inflammation. 

PMID- 25388269
TI  - The function of mast cells in autoimmune glomerulonephritis.
AB  - Immune-mediated glomerulonephritis is caused by deposition of immune complexes on
      the glomerular basement membrane or of autoantibodies directed against the
      glomerular basement membrane. Depositions lead to an inflammatory response that
      can ultimately destroy renal function and lead to chronic kidney disease.
      However, the pathological processes leading to the development of renal injury
      and disease progression remain poorly understood. To investigate the mechanisms
      of disease development in glomerulonephritis various animal models have been
      developed, which include as the most popular one the induction of
      glomerulonephritis by the injection of heterologous antibodies directed to the
      glomerular basement membrane. The role of mast cells and mast cell-derived
      mediators has been evaluated in these models. In this chapter we describe the
      methods that allow to set up and study the disease parameters of immune-mediated
      glomerulonephritis development. 

PMID- 25388270
TI  - A mouse model of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic or chronically relapsing, pruritic
      inflammatory skin disease. The incidence of AD has dramatically increased for the
      past three decades in industrialized countries. We established a highly efficient
      method to induce AD-like skin lesions using repeated epicutaneous treatments with
      house dust mite allergen and staphylococcal enterotoxin B (SEB). The dermatitis
      induced mice showed increased serum IgE levels that were similar to human AD
      patients and also treatable with dexamethasone. This mouse AD model has been used
      in a vaccinia virus infection study. It will also be useful to study pathogenic
      processes of AD and to evaluate the efficacy of a drug candidate. In this
      chapter, we describe the detailed method that can induce AD-like skin
      inflammation in multiple mouse strains. 

PMID- 25388271
TI  - Mouse models of allergic asthma.
AB  - In the last 20 years, the development of murine models of allergic asthma has
      provided researchers with a means to explore the mechanisms of this T-helper type
      2 (Th2)-driven inflammatory disease. While systemic sensitization and airway
      challenge with ovalbumin has been the most widely used model, recent emphasis has
      been placed on the development of models using more naturally occurring antigens.
      However, the diversity of models currently available makes it hard for
      investigators new to this field to choose to use the most effective and
      appropriate model to test their hypothesis. Here we describe three different
      mouse models of allergic asthma, including the classical ovalbumin model, a
      modified ovalbumin model that has been shown to be mast-cell dependent, as well
      as a house dust mite antigen-induced model. We also discuss briefly their
      characterization and differences, in the aim to facilitate the choice of the
      appropriate model when working on this intricate Th2 inflammatory disease. 

PMID- 25388272
TI  - Methods in assessment of airway reactivity in mice.
AB  - Due to the wealth of reagents and transgenic strains available, mice have become
      one of the most commonly used model organisms for the study of allergic airway
      inflammation. One of the major hallmarks of the asthma phenotype in humans is
      reversible airflow obstruction, or airway hyper-responsiveness. However, the
      ability to confidently obtain useful physiological responses from such a small
      animal has presented a large technological challenge in murine studies. Recent
      advances have provided the technology to obtain lung mechanics through either the
      forced oscillation technique or plethysmography. Here we describe the utility of
      these measurements in mouse models of allergic airway inflammation and
      anaphylaxis. 

PMID- 25388274
TI  - An omnibus test for several hazard alternatives in prevention randomized
      controlled clinical trials.
AB  - The logrank test is optimal for testing the equality of survival distributions
      against a proportional hazards alternative. Under a late effects alternative, it
      is no longer appropriate, and one may turn to Fleming-Harrington's class of
      weighted logrank tests instead. In some settings, such as in preventive clinical
      trials where the statistical analysis has to be designed before the trial begins,
      it can be difficult to choose a priori between the logrank and Fleming-Harrington
      tests. A solution to this issue is provided. A decision rule is constructed for
      the problem of testing the equality of two survival distributions when the
      expected alternative may be one of the proportional hazards and late effects. A
      formula for computing the necessary sample size is obtained for this decision
      rule. A comprehensive simulation study is conducted to assess finite sample
      properties of the proposed test statistic. The proposed test improves both the
      logrank test and Fleming-Harrington's test for late effects. Finally, the
      methodology is illustrated on a data set in the field of prevention of
      Alzheimer's disease.

PMID- 25388273
TI  - Geriatric hospitalizations in fall-related injuries.
AB  - BACKGROUND: To investigate the injury pattern, severity, and mortality of elderly
      patients hospitalized for treatment of trauma following fall accidents. METHODS:
      Data obtained from the Trauma Registry System were retrospectively reviewed for
      trauma admissions between January 1, 2009 and December 31, 2013 in a Level I
      trauma center. Of 16,548 registered patients, detailed information was retrieved
      from the 2,403 elderly patients (aged 65 years and above) with fall accidents and
      was compared with information from 1,909 adult patients (aged 20-64) with fall
      accidents. RESULTS: Falls presented the major mechanism for admission (59.9%) in
      the elderly patients. The number of elderly patients who fell from a height <1 m
      was greater than that of the adult patients (91.9% vs. 62.5%, respectively, p
      <0.001). The Injury Severity Score (ISS) (9.3 +/- 4.4 vs. 8.3 +/- 6.1,
      respectively, p =0.007) and New Injury Severity Score (NISS) (10.3 +/- 6.8 vs.
      9.5 +/- 8.2, respectively, p <0.001) were significantly higher in the elderly
      than the adult patients. A significantly larger proportion of the elderly
      patients were admitted to the ICU (16.2% vs. 13.4%, respectively, p =0.009), and
      the elderly were found to have longer stays in the intensive care unit (ICU) (8.6
      days vs. 7.6 days, respectively, p =0.034) but not in the hospital in general
      (9.6 days vs. 8.5 days, respectively, p =0.183). Additionally, a significantly
      higher percentage of the elderly patients sustained subdural hematoma (10.1% vs.
      8.2%, respectively, p =0.032) and femoral fracture (50.6% vs. 14.1%,
      respectively, p <0.001). There were significant differences in in-hospital
      mortality (18.2% vs. 10.3%, respectively, p =0.031) and length of stay in the
      hospital (11.6 days vs. 14.9 days, respectively, p =0.037) between the elderly
      and adult patients with subdural hematoma, but not between those with femoral
      fracture. CONCLUSIONS: Analysis of the data indicates that elderly patients
      hospitalized for treatment of trauma following fall accidents present with a
      bodily injury pattern that differs from that of adult patients and have a higher
      severe injury score, worse outcome, and higher mortality than those of adult
      patients.

PMID- 25388275
TI  - Ultrasonographic imaging of the sciatic nerve in a patient with knife injury.

PMID- 25388276
TI  - Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during
      withdrawal from prolonged alcohol exposure.
AB  - Both human and animal studies indicate that alcohol withdrawal following chronic
      alcohol consumption (CAC) impairs many of the cognitive functions which rely on
      the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory
      deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive
      element binding (CREB) cascade, although the role of PKA/CREB cascade in
      behavioral and molecular changes during sustained withdrawal period remains
      largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal
      after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation
      task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1
      region (dCA1) of the hippocampus compared with CAC and water conditions. In
      contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased
      pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared
      with water controls. Next, we showed that enhancing CREB activity through
      rolipram administration prior to testing improved WM performance in withdrawn
      mice but impaired WM function in water mice. In addition, WM improvement
      correlates positively with increased pCREB level selectively in the PFC of
      withdrawn mice. Results further indicate that direct infusion of the PKA
      activator (Sp-cAMPS) into the PFC significantly improves or impairs,
      respectively, WM performance in withdrawn and water animals. In contrast, Sp
      cAMPS had no effect on WM when infused into the dCA1. Collectively, these results
      provide strong support that dysregulation of PKA/CREB-dependent processes in
      prefrontal neurons is a critical molecular signature underlying cognitive decline
      during alcohol withdrawal. 

PMID- 25388277
TI  - Increasing maternal prepregnancy body mass index is associated with reduced
      insulin sensitivity and increased blood pressure in their children.
AB  - OBJECTIVE: We aimed to assess the effects of maternal prepregnancy body mass
      index (BMI) on insulin sensitivity, metabolism and blood pressure in the
      offspring. METHODS: We studied 70 prepubertal children aged 8.9 +/- 1.9 years
      (range 4-11 years), born 38-40 weeks of gestation and appropriate-for-gestational
      age birthweight. Maternal prepregnancy body mass index (MPP BMI) was calculated
      from self-reported weight. Children's insulin sensitivity was measured using
      intravenous glucose tolerance tests and Bergman's minimal model. Other clinical
      assessments included auxology, fasting lipid and hormonal profiles, DXA-derived
      body composition and 24-h ambulatory blood pressure monitoring. Data were
      analysed using random effect mixed models, adjusting for important confounders
      and a random factor to account for sibling clusters. RESULTS: Increasing MPP BMI
      was correlated with increasing BMI standard deviation scores (SDS) (r = 0.30; P =
      0.012) and lower insulin sensitivity in their children (r = -0.34; P = 0.004). In
      multivariate regression models, increasing MPP BMI was associated with lower
      insulin sensitivity (beta = -0.040; P = 0.005), with every 1 kg/m(2) increase in
      MPP BMI associated with a 4.0% decrease in offspring insulin sensitivity. Greater
      MPP BMI was associated with higher systolic blood pressure in the daytime (beta =
      0.794; P = 0.010) and night-time (beta = 0.800; P = 0.017), as well as higher 24
      h mean arterial pressure (beta = 0.508; P = 0.025) in the offspring. CONCLUSION:
      Greater maternal prepregnancy BMI is associated with lower insulin sensitivity
      and higher blood pressure in their children, effects that were independent of
      offspring adiposity. Thus, higher maternal BMI prior to pregnancy (even among
      women of normal BMI) may contribute to increased risk of type 2 diabetes and
      other metabolic diseases in the subsequent generation.

PMID- 25388278
TI  - Deformation density components analysis of fullerene-based anti-HIV drugs.
AB  - Deformation density analysis is performed on fullerene-based anti-HIV agents to
      investigate the influence of charge redistribution on the capability of binding
      to HIV enzymes. Two types of HIV inhibitors including malonic acid- and amino
      acid-type C60 derivatives are considered to study. Total deformation density and
      its components including orbital relaxation and kinetic energy pressure are
      obtained for C60 derivatives. The deformation natural orbitals for each component
      of deformation density are assessed and their amounts of charge displacement are
      quantified to evaluate the binding affinity of HIV inhibitors. The results show
      that the orbital relaxation plays a more prominent role in deformation of
      electron density of studied compounds. Among the considered drugs, the amino acid
      type derivatives, N-(carboxymethyl)-2,5-dicarboxylic fulleropyrrolidines, show
      the most charge displacement. Moreover, the investigation into the deformation
      density of amino acid-type functional groups on C60 reveals that the connection
      of functional groups to the 5,6-ring junction results more displaced charge than
      the connection to the 6,6-ring junction. 

PMID- 25388279
TI  - DFT study of the effect of solvent on the H-atom transfer involved in the
      scavenging of the free radicals (.)HO2 and (.)O2(-) by caffeic acid phenethyl
      ester and some of its derivatives.
AB  - H-atom transfer from caffeic acid phenethyl ester (CAPE), MBC (3-methyl-2-butenyl
      caffeate), BC (benzoic caffeate), P3HC (phenethyl-3-hydroxycinnamate), and P4HC
      (phenethyl-4-hydroxycinnamate) to the selected free radicals (.)HO2 and (.)O2(-)
      was studied. Such a transfer can proceed in three different ways: concerted
      proton-coupled electron transfer (CPCET), electron transfer followed by proton
      transfer (ET-PT), and proton transfer followed by electron transfer (PT-ET). The
      latter pathway is sometimes competitive with SPLET (sequential proton loss
      electron transfer) in polar media. Analyzing the thermodynamic descriptors of the
      reactions of CAPE and its derivatives with co-reactive species-in particular, the
      free energies of reactions, the activation barrier to the CPCET mechanism, and
      their rate constants-appears to be the most realistic method of investigating the
      H-atom transfers of interest. These analyses were performed via DFT calculations,
      which agree well with the data acquired from experimental studies (IC50) and from
      CBS calculations. The CPCM solvation model was used throughout the work, while
      the SMD model-employed as a reference-was used only for CAPE. The main conclusion
      drawn from the analysis was that SPLET is the mechanism that governs the reaction
      of phenolic acids with (.)HO2, while PT-ET governs the reaction of phenols with
      (.)O2(-). In kinetic investigations of the CPCET process, the rate constant
      decreases as the solvent polarity increases, so the reaction velocity slows down.

PMID- 25388280
TI  - Prospective evaluation of PBC-specific health-related quality of life
      questionnaires in patients with primary sclerosing cholangitis.
AB  - BACKGROUND & AIMS: Primary biliary cirrhosis and Primary sclerosing cholangitis
      are autoimmune cholestatic liver diseases sharing a lot in common, including a
      significant impairment of patients' health-related quality of life HRQoL HRQoL in
      PBC is assessed with disease-specific PBC-40 and PBC-27 questionnaires. A PSC
      specific questionnaire has not been developed. Neither PBC-40 nor PBC-27s
      applicability for PSC has been evaluated. We applied these three questionnaires
      for HRQoL assessment in a large homogenous cohort of PSC patients. PATIENTS AND
      METHODS: This cross-sectional study enrolled 102 Caucasian PSCs and 53 matched
      healthy controls and measured HRQoL using generic SF-36, and disease-specific
      (PBC-40/PBC-27) questionnaires. RESULTS: (i) SF-36. Most SF-36 domains were
      significantly lower in PSCs than controls. Physical Functioning and Mental
      Component Summary scores were significantly lower in female patients and
      correlated negatively with age but not with concurrent inflammatory bowel
      disease. Cirrhosis was associated with lower Physical Functioning, Role Physical,
      General Health, Vitality and Physical Component Summary. (ii) PBC-40 and PBC-27.
      Both tools showed similar HRQoL impairment scoring. Fatigue and Cognitive were
      impaired in female patients. Several correlations existed between HRQoL and
      laboratory parameters, including cholestatic tests and Itch. Cirrhosis correlated
      with Other symptoms and Fatigue PBC-40. (iii) PBC-40 vs PBC-27. Strong
      correlations among most domains of both questionnaires were seen, as well as
      between (iv) SF-36 vs PBC-40 or SF-36 vs PBC-27. CONCLUSION: This is the first
      study directly comparing PBC-40, PBC-27 and SF-36 in PSC. PSC patients,
      especially females, show HRQoL impairment. PBC-40 and PBC-27 questionnaires could
      be of potential use for HRQoL assessment in PSC.

PMID- 25388281
TI  - Self-organizing behaviour of glycosteroidal bolaphiles: insights into lipidic
      microsegregation.
AB  - In this article we describe work on the synthesis of bolaphile biomimics composed
      of glucose head groups and steroidal units linked together by a methylene chain
      of varying length. The condensed phases formed by self-organization of the
      products as a function of temperature were characterized by differential scanning
      calorimetry and thermal polarized light microscopy. The results of these studies
      show that the thermal stabilities of the lamellar mesophases formed vary linearly
      as a function of increasing aliphatic composition, which reflects a linear
      hydrophobic-hydrophilic balance with respect to transition temperatures. 

PMID- 25388282
TI  - Bion and the sublime: the origins of an aesthetic paradigm.
AB  - In constructing his theory Bion drew on a number of symbolic matrices:
      psychoanalysis, philosophy, mathematics, literature, aesthetics. The least
      investigated of these is the last. True, we know that Bion cites many authors of
      the Romantic period, such as Coleridge, Keats, Blake and Wordsworth, as well as
      others who were held in high esteem in the Romantic period, such as Milton.
      However, less is known about the influence exerted on him by the aesthetics of
      the sublime, which while chronologically preceding Romanticism is in fact one of
      its components. My working hypothesis is that tracing a number of Bion's concepts
      back to this secret model can serve several purposes: firstly, it contributes to
      the study of the sources, and, secondly, it makes these concepts appear much less
      occasional and idiosyncratic than we might believe, being as they are mostly
      those less immediately understandable but not less important (O, negative
      capability, nameless dread, the infinite, the language of achievement, unison
      etc.). Finally, connecting these notions to a matrix, that is, disclosing the
      meaning of elements that are not simply juxtaposed but dynamically interrelated,
      in my view significantly increases not only their theoretical intelligibility but
      also their usefulness in clinical practice. In conclusion, one could legitimately
      argue that Bion gradually subsumed all the other paradigms he drew on within the
      aesthetic paradigm. 

PMID- 25388283
TI  - Loss of estrogen-regulated microRNA expression increases HER2 signaling and is
      prognostic of poor outcome in luminal breast cancer.
AB  - Among the genes regulated by estrogen receptor (ER) are miRNAs that play a role
      in breast cancer signaling pathways. To determine whether miRNAs are involved in
      ER-positive breast cancer progression to hormone independence, we profiled the
      expression of 800 miRNAs in the estrogen-dependent human breast cancer cell line
      MCF7 and its estrogen-independent derivative MCF7:2A (MCF7:2A) using NanoString.
      We found 78 miRNAs differentially expressed between the two cell lines, including
      a cluster comprising let-7c, miR99a, and miR125b, which is encoded in an intron
      of the long noncoding RNA LINC00478. These miRNAs are ER targets in MCF7 cells,
      and nearby ER binding and their expression are significantly decreased in MCF7:2A
      cells. The expression of these miRNAs was interrogated in patient samples
      profiled in The Cancer Genome Atlas (TCGA). Among luminal tumors, these miRNAs
      are expressed at higher levels in luminal A versus B tumors. Although their
      expression is uniformly low in luminal B tumors, they are lost only in a subset
      of luminal A patients. Interestingly, this subset with low expression of these
      miRNAs had worse overall survival compared with luminal A patients with high
      expression. We confirmed that miR125b directly targets HER2 and that let-7c also
      regulates HER2 protein expression. In addition, HER2 protein expression and
      activity are negatively correlated with let-7c expression in TCGA. In summary, we
      identified an ER-regulated miRNA cluster that regulates HER2, is lost with
      progression to estrogen independence, and may serve as a biomarker of poor
      outcome in ER(+) luminal A breast cancer patients.

PMID- 25388284
TI  - Akt1 and akt3 exert opposing roles in the regulation of vascular tumor growth.
AB  - Vascular tumors are endothelial cell neoplasms whose mechanisms of tumorigenesis
      are poorly understood. Moreover, current therapies, particularly those for
      malignant lesions, have little beneficial effect on clinical outcomes. In this
      study, we show that endothelial activation of the Akt1 kinase is sufficient to
      drive de novo tumor formation. Mechanistic investigations uncovered opposing
      functions for different Akt isoforms in this regulation, where Akt1 promotes and
      Akt3 inhibits vascular tumor growth. Akt3 exerted negative effects on tumor
      endothelial cell growth and migration by inhibiting activation of the translation
      regulatory kinase S6-Kinase (S6K) through modulation of Rictor expression. S6K in
      turn acted through a negative feedback loop to restrain Akt3 expression.
      Conversely, S6K signaling was increased in vascular tumor cells where Akt3 was
      silenced, and the growth of these tumor cells was inhibited by a novel S6K
      inhibitor. Overall, our findings offer a preclinical proof of concept for the
      therapeutic utility of treating vascular tumors, such as angiosarcomas, with S6K
      inhibitors.

PMID- 25388285
TI  - Paradoxical decrease in the capture and lymph node delivery of cancer vaccine
      antigen induced by a TLR4 agonist as visualized by dual-mode imaging.
AB  - Traditionally, cell-mediated immune responses to vaccination in animal models are
      evaluated by invasive techniques such as biopsy and organ extraction. We show
      here that by combining two noninvasive imaging technologies, MRI and
      bioluminescence imaging (BLI), we can visualize both the afferent and efferent
      arms of cellular events following vaccination longitudinally. To this end, we
      evaluated the immune response elicited by a novel Toll-like receptor 4 agonist
      vaccine adjuvant, glucopyranosyl lipid A (GLA), using a whole-cell tumor vaccine.
      After magnetovaccination, MRI was used to visualize antigen-presenting cell
      mediated antigen capture and subsequent migration to draining lymph nodes (DLN).
      Paradoxically, we observed that the incorporation of GLA in the vaccine reduced
      these critical parameters of the afferent immune response. For the efferent arm,
      the magnitude of the ensuing antigen-specific T-cell response in DLN visualized
      using BLI correlated with antigen delivery to the DLN as measured by MRI. These
      findings were confirmed using flow cytometry. In spite of the GLA-associated
      reduction in antigen delivery to the DLN, however, the use of GLA as a vaccine
      adjuvant led to a massive proliferation of vaccine primed antigen-specific T
      cells in the spleen. This was accompanied by an enhanced tumor therapeutic effect
      of the vaccine. These findings suggest that GLA adjuvant changes the temporal and
      anatomical features of both the afferent and efferent arms of the vaccine
      response and illustrates the utility of quantitative noninvasive imaging as a
      tool for evaluating these parameters during vaccine optimization.

PMID- 25388286
TI  - SYK is a candidate kinase target for the treatment of advanced prostate cancer.
AB  - Improved targeted therapies are needed to combat metastatic prostate cancer.
      Here, we report the identification of the spleen kinase SYK as a mediator of
      metastatic dissemination in zebrafish and mouse xenograft models of human
      prostate cancer. Although SYK has not been implicated previously in this disease,
      we found that its expression is upregulated in human prostate cancers and
      associated with malignant progression. RNAi-mediated silencing prevented invasive
      outgrowth in vitro and bone colonization in vivo, effects that were reversed by
      wild-type but not kinase-dead SYK expression. In the absence of SYK expression,
      cell surface levels of the progression-associated adhesion receptors integrin
      alpha2beta1 and CD44 were diminished. RNAi-mediated silencing of alpha2beta1
      phenocopied SYK depletion in vitro and in vivo, suggesting an effector role for
      alpha2beta1 in this setting. Notably, pharmacologic inhibitors of SYK kinase
      currently in phase I-II trials for other indications interfered similarly with
      the invasive growth and dissemination of prostate cancer cells. Our findings
      offer a mechanistic rationale to reposition SYK kinase inhibitors for evaluation
      in patients with metastatic prostate cancer.

PMID- 25388287
TI  - Measuring calcium, potassium, and nitrate in plant nutrient solutions using ion
      selective electrodes in hydroponic greenhouse of some vegetables.
AB  - Generally, the life cycle of plants depends on the uptake of essential nutrients
      in a balanced manner and on toxic elements being under a certain concentration.
      Lack of control of nutrient levels in nutrient solution can result in reduced
      plant growth and undesired conditions such as blossom-end rot. In this study,
      sensitivity and selectivity tests for various polyvinylchloride (PVC)-based ion
      selective membranes were conducted to identify those suitable for measuring
      typical concentration ranges of macronutrients, that is, NO(3-), K(+), and
      Ca(2+), in hydroponic solutions. The sensitivity and selectivity of PVC-membrane
      based ion-selective sensors prepared with tetradodecylammoniumnitrate for NO(3-),
      valinomycin for K(+), and Ca ionophore IV for Ca(2+) were found to be
      satisfactory for measuring NO(3-), K(+), and Ca(2+) ions in nutrient solutions
      over typical ranges of hydroponic concentrations. Potassium, calcium, and nitrate
      levels that were utilized by cucumber and tomato seedlings in the greenhouse were
      different. The findings show that tomato plants consumed less amounts of nitrate
      than cucumber plants over the first 2 months of their growth. We also found that
      the potassium intake was higher than other nutritional elements tested for all
      plants.

PMID- 25388289
TI  - Accuracy and risk of malignancy for diagnostic categories in urine cytology at a
      large tertiary institution.
AB  - BACKGROUND: At a high-volume center, it became necessary to provide benchmarks
      for the accuracy and risk of malignancy per urine cytology diagnostic category.
      The additive sensitivity for the determination of the residual risk of disease
      was calculated with the goal of determining the performance of cytology and
      optimal triage, including the number of urine samples, before the detection of
      malignancy in surveillance patients. METHODS: A 2-year laboratory information
      system-based search was conducted, and it yielded 587 subjects (695 biopsy and
      cytology pairs) with histological follow-up. The sensitivity and specificity of
      cytology for urothelial malignancy, the risk of malignancy per diagnostic
      category, the additive sensitivity, and the time for conversion from a negative
      initial cytology result to a positive cytology result were examined. RESULTS: The
      overall average sensitivity and specificity of cytology were 48.9% and 83.0%,
      respectively. The additive sensitivity increased with each subsequent cytology
      and peaked with the third cytology. A median conversion time of 22.2 months from
      a negative initial cytology result to a positive cytology result and a decline in
      predictive positive cytology after the fourth cytology were noted.
      Subcategorization of the atypical category failed to show statistical
      significance in predicting outcomes of biopsy. Surveillance subjects, as compared
      to primary subjects, showed a higher sensitivity for the detection of high and
      low grade cancers. CONCLUSIONS: The findings suggest that atypia favoring
      malignancy is being appropriately flagged. However, further definition of the
      atypical category is needed to increase specificity with a better qualitative or
      quantitative morphological algorithm. This study provides a risk of malignancy
      for each category for benchmarking and clinical triage. The data suggest that
      follow-up should include at least 4 consecutive urine specimens over a period of
      22.2 months.

PMID- 25388288
TI  - Inequities in accessibility to and utilisation of maternal health services in
      Ghana after user-fee exemption: a descriptive study.
AB  - INTRODUCTION: Inequities in accessibility to, and utilisation of maternal
      healthcare services impede progress towards attainment of the maternal health
      related Millennium Development Goals. The objective of this study is to examine
      the extent to which maternal health services are utilised in Ghana, and whether
      inequities in accessibility to and utilization of services have been eliminated
      following the implementation of a user-fee exemption policy, that aims to reduce
      financial barriers to access, reduce inequities in access, and improve access to
      and use of birthing services. METHODS: We analyzed data from the 2007 Ghana
      Maternal Health Survey for inequities in access to and utilization of maternal
      health services. In measuring the inequities, frequency tables and cross
      tabulations were used to compare rates of service utilization by region,
      residence and selected socio-demographic variables. RESULTS: Findings show
      marginal increases in accessibility to and utilisation of skilled antenatal,
      delivery and postnatal care services following the policy implementation (2003
      2007). However, large gradients of inequities exist between geographic regions,
      urban and rural areas, and different socio-demographic, religious and ethnic
      groupings. More urban women (40%) than rural, 53% more women in the highest
      wealth quintile than women in the lowest, 38% more women in the best performing
      region (Central Region) than the worst (Upper East Region), and 48% more women
      with at least secondary education than those with no formal education, accessed
      and used all components of skilled maternal health services in the five years
      preceding the survey. Our findings raise questions about the potential equity and
      distributional benefits of Ghana's user-fee exemption policy, and the role of non
      financial barriers or considerations. CONCLUSION: Exempting user-fees for
      maternal health services is a promising policy option for improving access to
      maternal health care, but might be insufficient on its own to secure equitable
      access to maternal health services in Ghana. Ensuring equity in access will
      require moving beyond user-fee exemption to addressing wider issues of supply and
      demand factors and the social determinants of health, including redistributing
      healthcare resources and services, and redressing the positional vulnerability of
      women in their communities.

PMID- 25388290
TI  - Anti-aversive role of the endocannabinoid system in the periaqueductal gray
      stimulation model of panic attacks in rats.
AB  - RATIONALE: Direct activation of the cannabinoid CB1 receptor in the dorsolateral
      periaqueductal gray (dlPAG) inhibits anxiety- and panic-related behaviours in
      experimental animals. It has remained unclear, however, whether the local
      endocannabinoid signalling is recruited as a protective mechanism against
      aversive stimuli. OBJECTIVES: The present study tested the hypothesis that the
      endocannabinoid system counteracts aversive responses in the dlPAG-stimulation
      model of panic attacks. METHODS: All drugs were infused into the dlPAG of rats.
      Local chemical stimulation with N-methyl-D-aspartate (NMDA, 1 nmol) was employed
      to induce panic-like behavioural and cardiovascular responses in freely moving
      and anaesthetized animals, respectively. The neuronal activity in the dlPAG was
      investigated by c-Fos immunohistochemistry. RESULTS: The selective CB1 receptor
      agonist, ACEA (0.005-0.5 pmol), prevented the NMDA-induced panic-like escape
      responses. More interestingly, increasing the local levels of endogenous
      anandamide with a fatty acid amide hydrolase (FAAH) inhibitor, URB597 (0.3-3
      nmol), prevented both the behavioural response and the increase in blood pressure
      induced by NMDA. The effect of URB597 (3 nmol) was reversed by the CB1 receptor
      antagonist, AM251 (0.1 nmol). Moreover, an otherwise ineffective and sub
      threshold dose of NMDA (0.5 nmol) was able to induce a panic-like response if
      local CB1 receptors were previously blocked by AM251 (0.1 nmol). Finally, URB597
      prevented the NMDA-induced neuronal activation of the dlPAG. CONCLUSIONS: The
      endocannabinoid system in the dlPAG attenuates the behavioural, cellular and
      cardiovascular consequences of aversive stimuli. This process may be considered
      for the development of additional treatments against panic and other anxiety
      related disorders.

PMID- 25388291
TI  - Role of nitric oxide in the behavioral and neurochemical effects of IB-MECA in
      zebrafish.
AB  - RATIONALE: The adenosine A3 receptor and the nitric oxide (NO) pathway regulate
      the function and localization of serotonin transporters (SERTs). These
      transporters regulate extracellular serotonin levels, which are correlated with
      defensive behavior. OBJECTIVE: The purpose of this study was to understand the
      role of the A3AR on anxiety and arousal models in zebrafish, and whether this
      role is mediated by the nitrergic modulation of serotonin uptake. METHODS: The
      effects of IB-MECA (0.01 and 0.1 mg/kg) were assessed in a series of behavioral
      tasks in adult zebrafish, as well as on extracellular serotonin levels in vivo
      and serotonin uptake in brain homogenates. Finally, the interaction between IB
      MECA and drugs blocking voltage-dependent calcium channels (VDCCs), NO synthase,
      and SERT was analyzed. RESULTS: At the lowest dose, IB-MECA decreased bottom
      dwelling and scototaxis, while at the highest dose, it also decreased shoaling,
      startle probability, and melanophore responses. These effects were accompanied by
      an increase in brain extracellular serotonin levels. IB-MECA also concentration
      dependently increased serotonin uptake in vitro. The effects of IB-MECA on
      extracellular 5-HT, scototaxis, and geotaxis were blocked by L-NAME, while only
      the effects on 5-HT and scototaxis were blocked by verapamil. In vitro, the
      increase in 5-HT uptake was dependent on VDCCs and NO. Finally, fluoxetine
      blocked the effect of IB-MECA on scototaxis, but not geotaxis. CONCLUSION: These
      results suggest that the effect of IB-MECA on scototaxis are mediated by a VDCC
      NO-SERT pathway. While NO seems to mediate the effects of IB-MECA on geotaxis,
      neither VDCCs nor SERT seems to be involved in this process.

PMID- 25388292
TI  - Nicotine effects in adolescence and adulthood on cognition and alpha4beta2
      nicotinic receptors in the neonatal ventral hippocampal lesion rat model of
      schizophrenia.
AB  - RATIONAL: Nicotine use in schizophrenia has traditionally been explained as "self
      medication" of cognitive and/or nicotinic acetylcholinergic receptor (nAChR)
      abnormalities. OBJECTIVES: We test this hypothesis in a neurodevelopmental rat
      model of schizophrenia that shows increased addiction behaviors including
      enhanced nicotine reinforcement and drug-seeking. METHODS: Nicotine transdermal
      patch (5 mg/kg/day vs. placebo * 10 days in adolescence or adulthood) effects on
      subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal
      nAChR densities (alpha4beta2; [3H]-epibatidine binding) were examined in neonatal
      ventral hippocampal lesion (NVHL) and SHAM-operated rats. RESULTS: NVHL cognitive
      deficits were not differentially affected by nicotine history compared to SHAMs.
      Nicotine history produced minimal cognitive effects while increasing food-reward
      consumption on the maze, compounding with NVHL-induced overconsumption. Acute
      nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest
      improvements in maze performance in rats with nicotine patch histories only, but
      not differentially so in NVHLs. Consistent with in vivo neuroimaging of beta2
      nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls,
      adult NVHLs showed 12% reductions in nAChR binding in MPFC (p < 0.05) but not
      ventral striatum (<5% changes, p > .40), whereas nicotine history elevated nAChRs
      across both regions (>30%, p < 0.001) without interacting with NVHLs. Adolescent
      vs. adult nicotine exposure did not alter nAChRs differentially. CONCLUSIONS:
      Although replicating nicotine-induced upregulation of nAChRs in human smokers and
      demonstrating NVHL validity in terms of schizophrenia-associated nAChR density
      patterns, these findings do not support hypotheses explaining increased nicotine
      use in schizophrenia as reflecting illness-specific effects of nicotine to
      therapeutically alter cognition or nAChR densities.

PMID- 25388294
TI  - An electronically enhanced chiral sum frequency generation vibrational
      spectroscopy study of lipid-bound cytochrome c.
AB  - Electronically enhanced chiral SFG spectroscopy was employed to study the lipid
      bound cyt c in situ. It was directly observed that upon interacting with anionic
      phospholipids, the amino acid residues around the heme adopted the beta-sheet
      conformation. In addition, the orientation of this newly formed beta-sheet
      structure was found to be sensitive to the bulk pH. 

PMID- 25388293
TI  - WY14643 produces anti-depressant-like effects in mice via the BDNF signaling
      pathway.
AB  - RATIONALE: Current anti-depressants are clinically effective only after several
      weeks of administration and always produce side effects. OBJECTIVES: WY14643 is a
      selective agonist of peroxisome proliferator-activated receptor-alpha with
      neuroprotective and neurotrophic effects. Here, we investigated the anti
      depressant effects of WY14643 in mice models of depression. METHODS: We assessed
      the anti-depressant effects of WY14643 in the forced swim test (FST), tail
      suspension test (TST) and chronic social defeat stress (CSDS) model. Western
      blotting and immunohistochemistry studies were further performed to detect the
      effects of WY14643 on the brain-derived neurotrophic factor (BDNF) signaling
      pathway and hippocampal neurogenesis. The anti-BDNF antibody, BDNF signaling
      inhibitor, and tryptophan hydroxylase inhibitor were also used to explore the
      anti-depressant mechanisms of WY14643. RESULTS: WY14643 exhibited robust anti
      depressant effects in the FST and TST and also protected against the CSDS stress
      in mice models. Moreover, WY14643 reversed the stress-induced elevation of
      corticosterone, deficiency of BDNF signaling pathway, and hippocampal
      neurogenesis. Blockade of BDNF signaling cascade, not the monoaminergic system,
      abolished all the anti-depressant effects of WY14643. CONCLUSIONS: These data
      provide the first evidence that WY14643 exerts anti-depressant-like activity
      through promoting the BDNF signaling pathway.

PMID- 25388297
TI  - Correction.
AB  - [This corrects the article on p. 2541 in vol. 7, PMID: 24392395.]. 

PMID- 25388295
TI  - Molecular details of a starch utilization pathway in the human gut symbiont
      Eubacterium rectale.
AB  - Eubacterium rectale is a prominent human gut symbiont yet little is known about
      the molecular strategies this bacterium has developed to acquire nutrients within
      the competitive gut ecosystem. Starch is one of the most abundant glycans in the
      human diet, and E. rectale increases in vivo when the host consumes a diet rich
      in resistant starch, although it is not a primary degrader of this glycan. Here
      we present the results of a quantitative proteomics study in which we identify
      two glycoside hydrolase 13 family enzymes, and three ABC transporter solute
      binding proteins that are abundant during growth on starch and, we hypothesize,
      work together at the cell surface to degrade starch and capture the released
      maltooligosaccharides. EUR_21100 is a multidomain cell wall anchored amylase that
      preferentially targets starch polysaccharides, liberating maltotetraose, whereas
      the membrane-associated maltogenic amylase EUR_01860 breaks down
      maltooligosaccharides longer than maltotriose. The three solute-binding proteins
      display a range of glycan-binding specificities that ensure the capture of
      glucose through maltoheptaose and some alpha1,6-branched glycans. Taken together,
      we describe a pathway for starch utilization by E. rectale DSM 17629 that may be
      conserved among other starch-degrading Clostridium cluster XIVa organisms in the
      human gut. 

PMID- 25388296
TI  - Estimation of step-by-step spatio-temporal parameters of normal and impaired gait
      using shank-mounted magneto-inertial sensors: application to elderly,
      hemiparetic, parkinsonian and choreic gait.
AB  - BACKGROUND: The step-by-step determination of the spatio-temporal parameters of
      gait is clinically relevant since it provides an estimation of the variability of
      specific gait patterns associated with frequent geriatric syndromes. In recent
      years, several methods, based on the use of magneto-inertial units (MIMUs), have
      been developed for the step-by-step estimation of the gait temporal parameters.
      However, most of them were applied to the gait of healthy subjects and/or of a
      single pathologic population. Moreover, spatial parameters in pathologic
      populations have been rarely estimated step-by-step using MIMUs. The validity of
      clinically suitable MIMU-based methods for the estimation of spatio-temporal
      parameters is therefore still an open issue. The aim of this study was to propose
      and validate a method for the determination of both temporal and spatial
      parameters that could be applied to normal and heavily compromised gait patterns.
      METHODS: Two MIMUs were attached above each subject's ankles. An instrumented
      gait mat was used as gold standard. Gait data were acquired from ten hemiparetic
      subjects, ten choreic subjects, ten subjects with Parkinson's disease and ten
      healthy older adults walking at two different gait speeds. The method detects
      gait events (GEs) taking advantage of the cyclic nature of gait and exploiting
      some lower limb invariant kinematic characteristics. A combination of a MIMU axes
      realignment along the direction of progression and of an optimally filtered
      direct and reverse integration is used to determine the stride length. RESULTS:
      Over the 4,514 gait cycles analyzed, neither missed nor extra GEs were generated.
      The errors in identifying both initial and final contact at comfortable speed
      ranged between 0 and 11 ms for the different groups analyzed. The stride length
      was estimated for all subjects with less than 3% error. CONCLUSIONS: The proposed
      method is apparently extremely robust since gait speed did not substantially
      affect its performance and both missed and extra GEs were avoided. The spatio
      temporal parameters estimates showed smaller errors than those reported in
      previous studies and a similar level of precision and accuracy for both healthy
      and pathologic gait patterns. The combination of robustness, precision and
      accuracy suggests that the proposed method is suitable for routine clinical use.

PMID- 25388298
TI  - Bidirectional-Compounding Effects of Rumination and Negative Emotion in
      Predicting Impulsive Behavior: Implications for Emotional Cascades.
AB  - Influenced by chaos theory, the emotional cascade model proposes that rumination
      and negative emotion may promote each other in a self-amplifying cycle that
      increases over time. Accordingly, exponential-compounding effects may better
      describe the relationship between rumination and negative emotion when they occur
      in impulsive persons, and predict impulsive behavior. Forty-seven community and
      undergraduate participants who reported frequent engagement in impulsive
      behaviors monitored their ruminative thoughts and negative emotion multiple times
      daily for two weeks using digital recording devices. Hypotheses were tested using
      cross-lagged mixed model analyses. Findings indicated that rumination predicted
      subsequent elevations in rumination that lasted over extended periods of time.
      Rumination and negative emotion predicted increased levels of each other at
      subsequent assessments, and exponential functions for these associations were
      supported. Results also supported a synergistic effect between rumination and
      negative emotion, predicting larger elevations in subsequent rumination and
      negative emotion than when one variable alone was elevated. Finally, there were
      synergistic effects of rumination and negative emotion in predicting number of
      impulsive behaviors subsequently reported. These findings are consistent with the
      emotional cascade model in suggesting that momentary rumination and negative
      emotion progressively propagate and magnify each other over time in impulsive
      people, promoting impulsive behavior. 

PMID- 25388299
TI  - A penalized algorithm for event-specific rate models for recurrent events.
AB  - We introduce a covariate-specific total variation penalty in two semiparametric
      models for the rate function of recurrent event process. The two models are a
      stratified Cox model, introduced in Prentice and others (1981. On the regression
      analysis of multivariate failure time data. Biometrika 68: , 373-379.), and a
      stratified Aalen's additive model. We show the consistency and asymptotic
      normality of our penalized estimators. We demonstrate, through a simulation
      study, that our estimators outperform classical estimators for small-to-moderate
      sample sizes. Finally, an application to the bladder tumor data of Byar (1980.
      The veterans administration study of chemoprophylaxis for recurrent stage 1
      bladder tumors: comparison of placebo, pyridoxine, and topical thiotepa. In
      Pavone-Macaluso, M. Smith, P. H. and F. Edsmyn (editors), Bladder Tumors and
      Others Topics in Urological Oncology, pp. 363-370.) is presented. 

PMID- 25388302
TI  - Gender Differences in Liking and Wanting Sex: Examining the Role of Motivational
      Context and Implicit Versus Explicit Processing.
AB  - The present study investigated the specificity of sexual appraisal processes by
      making a distinction between implicit and explicit appraisals and between the
      affective (liking) and motivational (wanting) valence of sexual stimuli. These
      appraisals are assumed to diverge between men and women, depending on the context
      in which the sexual stimulus is encountered. Using an Implicit Association Test,
      explicit ratings, and film clips to prime a sexual, romantic or neutral
      motivational context, we investigated whether liking and wanting of sexual
      stimuli differed at the implicit and explicit level, differed between men and
      women, and were differentially sensitive to context manipulations. Results showed
      that, at the implicit level, women wanted more sex after being primed with
      romantic mood whereas men showed the least wanting of sex in the romantic
      condition. At the explicit level, men reported greater liking and wanting of sex
      than women, independently of context. We also found that women's (self-reported)
      sexual behavior was best predicted by the incentive salience of sexual stimuli
      whereas men's sexual behavior was more closely related to the hedonic qualities
      of sexual stimuli. Results were discussed in relation to an emotion-motivational
      account of sexual functioning. 

PMID- 25388301
TI  - [Hygiene measures in the intensive care station].
AB  - Medical personnel in intensive care units (ICU) deal with critically ill patients
      and a high work load. Patients face a higher risk of acquiring a nosocomial
      infection during their ICU stay. Especially, invasively ventilated patients are
      threatened. A catheter-related bloodstream infection might even lead to more
      severe complications. The number of multiresistant pathogens continues to rise;
      thus, comprehensive infection control measures are crucial to avoid pathogen
      transmission and infection. The most important measure is hand disinfection. With
      a proper personnel-patient ratio, educational programs, and infection control
      bundles, it is possible to reduce infection rates and enhance compliance among
      health care workers. 

PMID- 25388303
TI  - An Experimental Study of Men's and Women's Personal Ads.
AB  - Personal ads have long served as a potentially rich source of information for
      social scientists regarding what women and men appear to be looking for in a
      partner and what they believe potential partners are looking for in them. Almost
      every study of this type has content analyzed existing personal ads in print
      media or, more recently, on the Internet. Many of the limits of this research
      approach were addressed in a study by Strassberg and Holty (2003) utilizing an
      experimental research design. Contrary to theory, prior research, and prediction,
      the most popular female seeking male (FSM) ad in that study was one in which the
      woman described herself as "financially independent, successful [and] ambitious,"
      producing over 50 % more responses than the next most popular ad, describing the
      writer as "very attractive and slim." The present study replicated the Strassberg
      and Holty methodology, placing the same fictitious MSF and FSM personal ads using
      far more accessible Internet personal ad sites. Contrary to the previous finding,
      but consistent with evolutionary theories and social psychological experiments
      (e.g., Townsend & Wasserman, 1998), ads that presented the woman as attractive
      and the man as financially successful elicited the most interest.

PMID- 25388304
TI  - EpiVix: Brazilian epidemiology in transition.

PMID- 25388305
TI  - Health legislation and democratic rule of law in Brazil.

PMID- 25388306
TI  - Health in the post-2015 agenda: perspectives midway through.

PMID- 25388307
TI  - Name segmentation using hidden Markov models and its application in record
      linkage.
AB  - This study aimed to evaluate the use of hidden Markov models (HMM) for the
      segmentation of person names and its influence on record linkage. A HMM was
      applied to the segmentation of patient's and mother's names in the databases of
      the Mortality Information System (SIM), Information Subsystem for High Complexity
      Procedures (APAC), and Hospital Information System (AIH). A sample of 200
      patients from each database was segmented via HMM, and the results were compared
      to those from segmentation by the authors. The APAC-SIM and APAC-AIH databases
      were linked using three different segmentation strategies, one of which used HMM.
      Conformity of segmentation via HMM varied from 90.5% to 92.5%. The different
      segmentation strategies yielded similar results in the record linkage process.
      This study suggests that segmentation of Brazilian names via HMM is no more
      effective than traditional segmentation approaches in the linkage process. 

PMID- 25388308
TI  - [Translation, cross-cultural adaptation, and content validation of the Portuguese
      version of the Coping Behaviours Inventory (CBI) for the Brazilian population].
AB  - Coping skills correlate directly with the success of alcohol abstinence. Brazil
      previously lacked an instrument to identify alcohol users' specific coping
      skills. The current study therefore aimed to perform the translation, cross
      cultural adaptation, and content validation of the Coping Behaviours Inventory
      (CBI). Procedures included translation and back-translation, cross-cultural
      adaptation, content evaluation, and a pilot study. The final Portuguese version
      was administered by telephone to 40 alcohol users seeking help through a
      telephone hotline called VIVAVOZ. The retranslated version was close to the
      original. As for content validation, most of the items proved satisfactory and
      acceptable. The theoretical dimension showed a mean kappa index of 0.666 between
      evaluators, which was considered a substantial level of agreement. The results
      were satisfactory and acceptable, demonstrating that the inventory is appropriate
      for investigating coping skills in Brazilian alcohol users.

PMID- 25388309
TI  - ["Raw and charred flesh": the experience of burned women in Northeast Brazil].
AB  - In Northeast Brazil, death from burns is a widespread, pervasive threat to poor
      women. This anthropological study describes the experience of personal suffering
      among female burn patients. In 2009, six "information-rich" cases were
      investigated at the Burn Center in Fortaleza, Ceara State, Brazil. Open
      ethnographic interviews with key informants, narratives of lived experiences, and
      participant observation at the clinic and patients' home were conducted. The
      methods included content analysis, systems of signs, meanings, and actions, and
      contextualized semantic interpretation. The emerging metaphors are embued with
      the cultural meaning of "monstrosity" and gender violence by fire - inscribed
      mercilessly in the woman's body. "Accidents" caused by flammable liquids
      (alcohol) hide the cruel reality of "raw and charred flesh". The scars can
      disfigure the victims as "non-persons", destroying their moral reputation and
      leading to social rejection. In the Brazilian Northeast, the social vulnerability
      caused by sequelae from burns demands a policy for humanized care.

PMID- 25388310
TI  - [Evaluation of information systems on live births and mortality in Brazil in the
      2000s].
AB  - The Brazilian Ministry of Health's mortality and live birth information systems
      (SIM and SINASC) are valuable tools for measuring population health status. The
      purpose of this study was to assess the adequacy of vital information systems
      from 1999-2001 to 2008-2010 in the States and major geographic regions of Brazil.
      Indicators were constructed to assess data coverage, regularity, and quality for
      SIM and SINASC. The municipalities (counties) were divided into three categories
      according to adequacy of data on deaths and live births by calculating an
      adequacy index based on the proportion of the population living in each category.
      The adequacy index for Brazil increased from 73.9 to 89.1 in the SIM and from
      80.5 to 90.9 in the SINASC from the first to the second triennium, respectively.
      Improvements occurred in all the indicators, in all regions of the country, and
      in most States. Analysis of the adequacy of vital information in Brazil showed
      clear improvement throughout the country, particularly in States of the North and
      Northeast regions.

PMID- 25388311
TI  - Mapping of capacities for research on health and its social determinants in
      Brazil.
AB  - This article describes tendencies in research on social determinants of health
      (SDH) and health inequities in Brazil (2005-2012) and maps research system
      structures to analyze capacities for research on health and its social
      determinants. Brazil has a strong national research system and counts on a wealth
      of research in the field of SDH drawing on a long tradition of research and
      political commitment in this area. While innovative strategies seeking to
      strengthen the links between research, policy and practice have been developed,
      the impact of SDH research continues to be largely restricted to the academic
      community with notable but still insufficient repercussions on public policy and
      the social determinants of health inequities. SDH research in Brazil will
      therefore need to become even more responsive to social urgencies and better
      attuned to political processes, enhancing its capacity to influence strategic
      policy decisions affecting health inequities and mobilize strategic agendas for
      health equity.

PMID- 25388312
TI  - [Kidney transplant patients without social protection in health: what do patients
      say about the economic hardships and impact?].
AB  - Kidney transplant is the optimal treatment for renal disease according to
      biomedical criteria, but the technology is highly expensive. The aim of this
      article was to examine the economic hardships experienced by kidney transplant
      patients and the impact on their lives, specifically when they lack social
      protection in health. The article reports on a qualitative study conducted in
      Mexico. Twenty-one kidney transplant patients participated. Semi-structured
      interviews were performed and submitted to content analysis. Patients experience
      extreme economic hardship due to the high cost of renal therapies, particularly
      medicines. Such economic problems adversely affect their condition, since many
      patients report difficulties in maintaining their immunosuppressant medication,
      attending medical appointments, and curtailing household expenditures, further
      aggravated by loss of earnings. In conclusion, kidney transplantation is
      associated with patients' impoverishment when they lack social protection in
      health. A protection system is urgently needed for this group.

PMID- 25388313
TI  - Intervention analysis of introduction of rotavirus vaccine on hospital admissions
      rates due to acute diarrhea.
AB  - The aim of this study is to investigate the impact of rotavirus vaccine on
      hospitalization rates for acute diarrhea in children younger than 5 years old
      after the introduction of the vaccine in 2006. A descriptive analytical
      observational study was carried out of the hospitalization rates occurred between
      2000 and 2011 in 22 Regional Health Centers of Parana State, Brazil. The effect
      of the vaccine was assessed by applying the SARIMA/Box-Jenkins time series
      methodology of intervention analysis, which allows verifying the slopes of the
      series are different after the introduction of the vaccine and estimating the
      magnitude of these effects for children younger than five years of age, by age
      group, for each region center. It was verified a statistically significant
      reduction by center/month on hospitalization rates for children 1 year old and
      younger, with averages of 47% and 58%, respectively, in December 2011.

PMID- 25388314
TI  - [Workplace violence in the healthcare sector: the experience of State health
      employees in Bahia State, Brazil].
AB  - This study aimed to estimate the prevalence of self-reported violence suffered by
      healthcare workers, using a cross-sectional design with a sample of 679 State
      health employees through face-to-face interviews and a questionnaire. Of the
      respondents, 25.9% (95%CI: 22.6%-29.2%) reported having suffered at least one
      form of violence, with verbal aggression as the most frequent (19.4%). Women aged
      25-39 suffered 80% more violence than older women (OR = 1.8; 95%CI: 1.1-3.0).
      Female physicians were the most frequently affected group (OR = 2.5; 95%CI: 1.2
      12.5). Among men, a nearly fourfold increase in healthcare workplace violence was
      associated with age 25 to 39 years (OR = 3.9; 95%CI: 1.9-16.4) and nurse
      assistants or nurse technicians (PR = 3.9; 95%CI: 1.1-13.2). This study can help
      raise awareness concerning healthcare workplace violence and support policies for
      health workers' care, with repercussions on quality of care for health services
      users.

PMID- 25388315
TI  - Body composition assessment using DXA in six-year-old children: the 2004 Pelotas
      Birth Cohort, Rio Grande do Sul State, Brazil.
AB  - The aim of this study was to describe fat (FM) and lean body mass (LBM) in six
      year-old children from the 2004 Pelotas Birth Cohort, stratified by gender. Dual
      Energy X-ray Absorptiometry was used to measure FM and LBM, FM and LBM indexes,
      and percentage (%) of FM and LBM. Mean measures of adiposity were higher among
      girls (6.3 kg, 4.2 kg/m(2) and 23.4% vs. 5 kg, 3.3 kg/m(2) and 18%) while LBM
      measures were higher among boys (19.3 kg, 13 kg/m(2) and 78.5% vs. 17.7 kg, 12.2
      kg/m(2) and 73.2%). In both boys and girls mean measures of adiposity increased
      with socioeconomic status and maternal education. Mean measures of adiposity were
      higher among white-skinned children while %LBM was higher among black-skinned
      children. Preterm compared to full-term children showed lower mean measures of
      adiposity and LBM. Female sex, white skin color and higher socioeconomic
      conditions are associated with higher adiposity in childhood.

PMID- 25388316
TI  - [Study of knowledge, attitudes, and practices related to leishmaniasis: evidence
      of government neglect in the Colombian Darien].
AB  - American cutaneous leishmaniasis (ACL) is considered a public health problem
      worldwide, and incidence in Colombia is 12,000 cases per year. Colombia has
      implemented control programs for years which have often overlooked the social,
      economic, and demographic characteristics of the regions where the disease
      occurs. As part of an epidemiological study, this article presents the results of
      a survey on knowledge, attitudes, and practices (KAP) related to leishmaniasis in
      rural populations in Acandi in the Colombian Darien. Qualitative and quantitative
      tools were used (ethnography and surveys, respectively). The results show scarce
      knowledge among the population on basic aspects such as recognition of the sand
      fly vector. There were also differences in KAP according to gender and type of
      population, rather than by geographic area. The study points to government
      neglect as a critical factor in the persistence of the disease.

PMID- 25388317
TI  - [An analysis of psychosocial care for adolescents in crisis based on their
      therapeutic itineraries].
AB  - This study analyzes the care provided to adolescents in crisis in a municipality
      in Greater Metropolitan Rio de Janeiro, Brazil. The article reports on a
      qualitative health study that used Therapeutic Itinerary and Life Narratives as
      the methodological resources. The principal theoretical reference was
      psychoanalyst Rene Kaes. Based on the adolescents' own verbal accounts, the study
      aimed to grasp the collective realities that could potentially shed light on the
      different types of logic and professional practices applied to care for
      adolescents in psychosocial crisis situations. The underlying assumption was that
      an approach to the dialectical nature of the crisis required maintaining a
      framework that would allow establishing a space for transition within which to
      develop the necessary conditions for disruptive and paradoxical elements to be
      elaborated. However, crisis care in the context studied here proved to be
      hampered by infrastructure issues, institutional rigidity, and fragmentation of
      activities, with little orientation towards inter-sector work.

PMID- 25388318
TI  - Characteristics of physical activity programs in the Brazilian primary health
      care system.
AB  - The aim of this study was to describe the characteristics of programs that
      promote physical activity in the public primary care system by region of Brazil,
      subject to the presence or absence of multidisciplinary primary care teams
      (NASF). We conducted a cross sectional and population-based telephone survey of
      the health unit coordinators from 1,251 health care units. Coordinators were
      asked about the presence and characteristics of physical activity programs. Four
      out of ten health units reported having a physical activity intervention program,
      the most common involving walking groups. Most of the activities were performed
      in the morning, once or twice a week, and in sessions of 30 minutes or more.
      Physical education professionals were primarily responsible for directing the
      activities. Interventions occurred in the health unit itself or in adjacent
      community spaces. In general, these characteristics were similar between units
      with or without NASF, but varied substantially across regions. These findings
      will guide future physical activity policies and programs within primary care in
      Brazil.

PMID- 25388319
TI  - [Absenteeism due to occupational diseases among sugarcane workers].
AB  - The aim of this study was to analyze the frequency of work-related sick leave in
      sugarcane workers. A total of 1,230 medical excuses for 400 sugarcane workers
      were analyzed according to the International Classification of Diseases, 10th
      Revision (ICD-10). The following items were analyzed: diagnosis, sex, and length
      and season of sick leave. In all the seasons, musculoskeletal diseases showed the
      highest sick leave rate, following by respiratory diseases (p < 0.05). Sick leave
      due to musculoskeletal diseases was more frequent at the end of the sugarcane
      harvest than during the intercrop season (p < 0.05). Seventy-five percent of
      medical excuses were for one day. The longest sick leaves were for diseases of
      the genitourinary tract (p < 0.001). It is thus essential to have a
      multidisciplinary health team focused on the development of ergonomic activities,
      personal protective equipment, and health orientation specifically targeting this
      group's needs.

PMID- 25388320
TI  - [Sex assignment in intersex children: a brief analysis of "ambiguous genitalia"
      cases].
AB  - This article takes an ethical approach to briefly analyze current therapeutic
      guidelines in Brazil for cases diagnosed as "ambiguous genitalia" (one of the
      "disorders of sexual development", DSD) in intersex children. Except when there
      is clear risk to the infant's life, there is no medical or institutional
      consensus on the definition of intersex, DSD, or recommended treatment. Parents
      or guardians of these minors have the legal right to provide consent for genital
      surgical interventions. The irreversibility of some procedures calls attention to
      reports by some intersex adults who underwent such interventions during their
      childhood or adolescence and now fail to acknowledge the physical or psychosocial
      benefits that were originally claimed to justify them.

PMID- 25388321
TI  - [How do physical fitness and heavy physical work interact in the occurrence of
      musculoskeletal disorders?].
AB  - A cross-sectional study investigated the association between self-reported
      physical fitness and musculoskeletal disorders in the neck, shoulder, or upper
      back among workers in 14 plastics factories in Salvador, Bahia State, Brazil.
      Physical fitness was assessed on a scale from 0 to 5. Cases were defined as self
      reported pain in the previous 12 months, lasting more than a week or having
      monthly minimum frequency, with restrictions at work or seeking medical care, or
      where respondents' severity was greater than 2 (on a scale from 0 to 5). Logistic
      regression was performed to investigate statistical interaction between physical
      fitness and physical demands from work in the occurrence of musculoskeletal
      disorders. Precarious physical fitness resulted in 3.19 times greater odds of
      musculoskeletal disorders among workers exposed to light physical demands on the
      job. Among workers exposed to heavy physical demands, physical fitness failed to
      protect against musculoskeletal disorders. Heavy physical work was always
      associated with high prevalence of musculoskeletal disorders. Despite the
      importance of physical fitness, physical exercise programs should not be used to
      replace improvements in working conditions.

PMID- 25388322
TI  - ["Before and after CML": illness experiences and dimensions of chronic myeloid
      leukemia as a biographical disruption].
AB  - This article examines the illness experiences of patients with chronic myeloid
      leukemia (CML), focusing on dimensions that link the onset of the disease as a
      biographical disruption. This qualitative study was based on analysis of
      narratives by six patients 23 to 62 years of age who were users of the Brazilian
      Unified National Health System (SUS) and patients at a referral hospital for
      hematological care in Salvador, Bahia State, Brazil. The results reveal the
      experience of disruption in three categories: (1) the meanings of illness and CML
      as life-threatening, (2) physical and social disruption and stigmatizing
      experiences, and (3) the "before-and-after" perception of CML, focusing on
      changes in self, social relations, and daily life. The article concludes that the
      biographical, social, and health-system impacts (considering the cost of
      medication) update and extend issues such as access to treatment and confronting
      certainty and uncertainty, where patients struggle to draw on their everyday
      knowledge to deal with what is "known" about CML. 

PMID- 25388323
TI  - [Socioeconomic determinants of dental care during pregnancy in Cali, Colombia].
AB  - The objectives of this study were to determine the prevalence of dental care for
      pregnant women in Cali, Colombia, and to identify socioeconomic and health
      services factors associated with access to dental care during pregnancy. A cross
      sectional study was conducted in a sample of 993 postpartum women who had given
      birth in public and private clinics in 2012. Multivariate analysis showed that
      dental care was associated with: economic resources (86.6% sufficient resources
      versus 72.5% insufficient resources; OR = 1.8; 95%CI: 1.1-2.8), schooling (88%
      complete versus 74% incomplete secondary school, OR = 1.7; 95%CI: 1.1-2.7), and
      receiving information on oral health and dental care during prenatal care (86.4%:
      yes versus 42.9%: no, OR = 5.7; 95%CI: 3.1-10.0). Access to dental care was less
      frequent among pregnant women with low socioeconomic status as compared to those
      with better living conditions.

PMID- 25388324
TI  - [Social class, psychosocial occupational risk factors, and the association with
      self-rated health and mental health in Chile].
AB  - The objective of this study was to analyze the association between social class
      and psychosocial occupational risk factors and self-rated health and mental
      health in a Chilean population. A cross-sectional study analyzed data from the
      First National Survey on Employment, Work, Quality of Life, and Male and Female
      Workers in Chile (N = 9,503). The dependent variables were self-rated health
      status and mental health. The independent variables were social class (neo
      Marxist), psychosocial occupational risk factors, and material deprivation.
      Descriptive and logistic regression analyses were performed. There were
      inequalities in the distribution of psychosocial occupational risk factors by
      social class and sex. Furthermore, social class and psychosocial occupational
      risk factors were associated with unequal distribution of self-rated health and
      mental health among the working population in Chile. Occupational health
      interventions should consider workers' exposure to socioeconomic and psychosocial
      risk factors.

PMID- 25388325
TI  - Association between eating patterns and body mass index in a sample of children
      and adolescents in Northeastern Brazil.
AB  - The aim of this study was to assess the relationship between eating patterns and
      body mass index (BMI) in children and adolescents. This is a cross-sectional
      study of 1,247 male and female students, aged between 6 and 12, from public
      elementary schools in Sao Francisco do Conde, Bahia State, Brasil. BMI was used
      to analyze the children's nutritional status. Food consumption frequencies, in
      addition to demographic and socioeconomic information, were collected for each
      participant. Dietary patterns were identified through a factor analysis. The
      prevalence of overweight and obesity was 17.3% (10.2% overweight and 7.1% obese).
      Two eating patterns, "obesogenic" and "prudent", were identified. The former is
      characterized by sweets and sugars, typical Brazilian dishes, pastries, fast
      food, oils, milk, cereals, cakes, and sauces, and was positively associated with
      increased BMI (betai = 0.244; p = 0.018). An "obesogenic" dietary pattern was
      associated with increased BMI.

PMID- 25388328
TI  - Comparison between polypyridyl and cyclometalated ruthenium(II) complexes:
      anticancer activities against 2D and 3D cancer models.
AB  - The aim of this study was to illustrate the dramatically different anticancer
      activities between coordinatively saturated polypyridyl (1 a-4 a) and
      cyclometalated (1 b-4 b) ruthenium(II) complexes. The cyclometalated complexes 1
      b-4 b function as DNA transcription inhibitors, exhibiting switch-on cytotoxicity
      against a 2D cancer cell monolayer, whereas the polypyridyl complexes 1 a-4 a are
      relatively inactive. Moreover, complexes 1 b-4 b exhibit excellent cytotoxicity
      against 3D multicellular tumor spheroids (MCTSs), which serve as an intermediate
      model between in vitro 2D cell monolayers and in vivo 3D solid tumors. The
      hydrophobicity, efficient cell uptake, and nucleus targeting ability, as well as
      the high DNA binding affinity of complexes 1 b-4 b, likely contribute to their
      enhanced anticancer activity. We surmise that cyclometalation could be a
      universal approach to significantly enhance the anticancer activity of
      substituted polypyridyl Ru(II) complexes. We also suggest that 3D MCTSs may be a
      more practical platform for anticancer drug screening than 2D cancer monolayer
      approaches. 

PMID- 25388330
TI  - Are residents of mountain-top mining counties more likely to have infants with
      birth defects? The West Virginia experience.
AB  - BACKGROUND: Pooled 1996 to 2003 birth certificate data for four central states in
      Appalachia indicated higher rates of infants with birth defects born to residents
      of counties with mountain-top mining (MTM) than born to residents of non-mining
      counties (Ahern 2011). However, those analyses did not consider sources of
      uncertainty such as unbalanced distributions or quality of data. Quality issues
      have been a continuing problem with birth certificate analyses. We used 1990 to
      2009 live birth certificate data for West Virginia to reassess this hypothesis.
      METHODS: Forty-four hospitals contributed 98% of the MTM-county births and 95% of
      the non-mining-county births, of which six had more than 1000 births from both
      MTM and nonmining counties. Adjusted and stratified prevalence rate ratios (PRRs)
      were computed both by using Poisson regression and Mantel-Haenszel analysis.
      RESULTS: Unbalanced distribution of hospital births was observed by mining
      groups. The prevalence rate of infants with reported birth defects, higher in MTM
      counties (0.021) than in non-mining-counties (0.015), yielded a significant crude
      PRR (cPRR = 1.43; 95% confidence interval [CI] = 1.36-1.52) but a nonsignificant
      hospital-adjusted PRR (adjPRR = 1.08; 95% CI = 0.97-1.20; p = 0.16) for the 44
      hospitals. So did the six hospital data analysis ([cPRR = 2.39; 95% CI = 2.15
      2.65] and [adjPRR = 1.01; 95% CI, 0.89-1.14; p = 0.87]). CONCLUSION: No increased
      risk of birth defects was observed for births from MTM-counties after adjustment
      for, or stratification by, hospital of birth. These results have consistently
      demonstrated that the reported association between birth defect rates and MTM
      coal mining was a consequence of data heterogeneity. The data do not demonstrate
      evidence of a "Mountain-top Mining" effect on the prevalence of infants with
      reported birth defects in WV.

PMID- 25388331
TI  - [Chinese expert consensus on standardized assessment and diagnosis of chest
      pain].

PMID- 25388329
TI  - Activation of TLR-4 to produce tumour necrosis factor-alpha in neuropathic pain
      caused by paclitaxel.
AB  - BACKGROUND: Neuropathic pain is a common complication of treatment with the anti
      neoplastic drug paclitaxel. Animal studies suggest neuroinflammation and
      transient receptor potential channels TRPA1 and TRPV4 are involved in the
      pathogenesis of pain in this condition. However, how neuroinflammation and TRPA1
      and TRPV4 are linked to cause pain in paclitaxel-treated animals is not known.
      METHODS: Paclitaxel-induced pain was modelled by IP injection of paclitaxel (16
      mg/kg) once a week for 5 weeks. The role of toll-like receptor 4 (TLR-4) in
      tumour necrosis factor-alpha (TNF-alpha) production and the effect of TNF-alpha
      on the expression of TRPA1 and TRPV4 were evaluated in vitro and in vivo. TNF
      alpha signalling in dorsal root ganglion (DRG) was blocked by expressing soluble
      TNF receptor I (TNFsR) from a herpes simplex virus (HSV)-based vector (vTNFsR).
      RESULTS: Paclitaxel treatment increased the expression and release of TNF-alpha
      in satellite glial cells and increased the expression of TRPA1 and TRPV4 in DRG
      neurons in animals. In vitro, paclitaxel enhanced the expression and release of
      TNF-alpha in enriched primary satellite glial cells, an effect that was blocked
      by an inhibitor of TLR-4. Direct application of TNF-alpha to primary DRG neurons
      in culture up-regulated the expression of TRPA1 and TRPV4. In vivo, vector
      mediated TNFsR release from DRG neurons reduced paclitaxel-induced up-regulation
      of TRPA1 and TRPV4 expression and prevented paclitaxel-induced pain. CONCLUSION:
      These results suggest that paclitaxel activation of TLR-4 to cause release of TNF
      alpha from satellite glial cells increases the expression of TRPA1 and TRPV4 in
      DRG neurons to cause neuropathic pain.

PMID- 25388333
TI  - [Promoting chest pain center accreditation is an essential way to improve the
      management of acute myocardial infarction in China].

PMID- 25388332
TI  - [2014 China cholesterol education program experts recommendations on management
      of dyslipidemia].

PMID- 25388334
TI  - [Concept and goal of a designed chest pain center].

PMID- 25388335
TI  - [Impact of establishing regional collaborative network on reperfusion time and
      prognosis of patients with ST-segment elevated myocardial infarction admitting to
      community hospitals without percutaneous coronary intervention capacity].
AB  - OBJECTIVE: To investigate the impact of establishing regional collaborative
      network on reperfusion time and prognosis of patients with ST-segment elevated
      myocardial infarction (STEMI) admitting to community hospitals without
      percutaneous coronary intervention (PCI) capacity (Non-PCI hospital). METHODS: A
      regional collaborative network was developed, consisting of a PCI center and over
      30 Non-PCI hospitals and connected by a tele-transmitted real-time 12-lead
      electrocardiogram system. This system enables the cardiologists on duty in PCI
      center to help the physicians in the Non-PCI hospitals (network hospital) to
      confirm the diagnosis and choose a reperfusion strategy for STEMI patients. All
      cardiologists in PCI center and physicians in Non-PCI hospitals were trained to
      follow the flowchart of reperfusion strategies for STEMI patients to shorten the
      reperfusion time. The mean time from door of Non-PCI hospital to needle of
      thrombolysis (D-to-N), the mean time from door of PCI center to balloon (D-to-B)
      and the mean time from the first medical contact to balloon (FMC-to-B) and the 1
      year mortality were compared between the 20 months before and the 20 months after
      establishment of the regional collaborative network for patients with the first
      medical contact in three network hospitals. RESULTS: After establishment of the
      regional collaborative network, the mean D-to-N time was significantly shortened
      from (71 +/- 62) min to (28 +/- 9) min (P < 0.05), the rate of D-to-N below 30
      min was increased from 11% (2/18) to 74% (26/35); the mean FMC-to-B and the mean
      D-to-B time were remarkably reduced in both complementary percutaneous coronary
      intervention and transfer percutaneous coronary intervention patients (all P <
      0.05), the 1-year mortality post reperfusion was reduced from 15.1% (8/53) to
      7.0% (10/142) (P < 0.05). CONCLUSION: The establishment of regional collaborative
      network could shorten the perfusion time and reduce the 1-year mortality for
      STEMI patients presenting to Non-PCI hospitals.

PMID- 25388336
TI  - [Impact of new regional cooperative rescue model on first medical contact to
      balloon time and outcome in patients with ST-segment elevation myocardial
      infarction].
AB  - OBJECTIVE: To evaluate the effect of new regional cooperative rescue model on the
      first medical contact-to-balloon time and outcome in patients with ST-elevation
      myocardial infarction. METHOD: Patients with acute myocardial infraction (AMI)
      and onset time within 24 hours transferred from other hospitals to our clinic and
      underwent emergent percutaneous coronary intervention (PCI) between January 2010
      and January 2013 were included in this study. Patients were divided into two
      groups: regional cooperative treatment group (n = 230) and control group (n =
      168) according to whether the first contact clinic belongs to the regional
      cooperative rescue model or not. The first medical contact to balloon (FMC-to-B)
      time, door to balloon (D-to-B) time, referral time, cardiac function, mean cost,
      days of hospitalization, and major adverse cardiac event (MACE) during the 6
      months follow up were compared. RESULTS: Mean FMC-to-B time, D-to-B time and
      referral time were significantly decreased from (212 +/- 37), (107 +/- 18), (103
      +/- 23) min (control group) to (98 +/- 23), (25 +/- 7), (62 +/- 12) min
      respectively in regional cooperative treatment group. Mean medical cost (42 221
      (23 184, 77 768) RMB vs. 49 654 (25 126, 122 433) RMB) and days of
      hospitalization (7 (5, 13) days vs. 10 (6, 20) days) were also significantly
      lower in regional cooperative treatment group than in control group. At 6 months
      follow up, LVEF was significantly higher(54.9% +/- 8.6% vs. 48.9% +/- 9.1%, P =
      0.01), LVEDD ((48.9 +/- 5.7)mm vs.(51.4 +/- 6.0) mm, P < 0.01) as well as MACE
      rate (7.4% (17/230) vs. 17.9% (30/168) , P < 0.05) were significantly lower in
      regional cooperative treatment group than in control group. CONCLUSION: The
      regional cooperative rescue model can decrease the FMC-to-B time, improve cardiac
      function, and reduce both patients' financial burden and MACE in patients with
      acute myocardial infarction.

PMID- 25388337
TI  - [Integrated regional network construction for ST-segment elevation myocardial
      infarction care].
AB  - OBJECTIVE: To investigate the feasibility of establishing an integrated regional
      network for ST-segment elevation myocardial infarction (STEMI) care in China and
      evaluate the implementation effect of this network. METHODS: Based on real-time
      electrocardiogram transmission technology, we established an integrated regional
      network for STEMI care (IRN-STEMI) with Xiamen Heart Center as the core center,
      120 Emergency Systems, PCI-capable hospitals and other community health units as
      core elements of this network. Reperfusion treatment data of Xiamen Heart Center
      including the number of patients receiving primary percutaneous coronary
      intervention (PCI), the mean first medical contact to balloon (FMC-to-B) time,
      the mean door to balloon (D-to-B) time, the mean length of hospital stay, the
      mean medical cost and in-hospital mortality were compared before (n = 165) and at
      1 year after the built-up of IRN-STEMI (n = 343). RESULTS: Compared to pre-IRN
      STEMI era, primary PCI ratio (84.5% (290/343) vs. 75.5% (185/245)) were
      significantly increased post establishment of IRN-STEMI within the network (P =
      0.06). STEMI patients admitted in Xiamen Heart Center was significantly increased
      from 165 to 256, the annual mean FMC-to-B time ((110.3 +/- 34.0)min vs. (137.9 +/
      58.5) min, P < 0.01) and D-to-B ( (76.5 +/- 33.0) min vs. (107.3 +/- 38.0) min,
      P < 0.01) , as well as the mean medical cost were significantly decreased ( (51
      398 +/- 22 100) RMB vs. (56 970 +/- 24 593) RMB, P < 0.05), while the mean length
      of hospital stay ((9.0 +/- 4.3)d vs. (9.7 +/- 4.8)d, P > 0.05) and in-hospital
      mortality (3.1% (8/256) vs. 3.0% (5/165) , P > 0.05) remained unchanged before
      and after the setting of IRN-STEMI in Xiamen Heart Center. CONCLUSION:
      Establishment of an integrated regional network system for STEMI patients in
      China is feasible. With collaboration of qualified heart center, EMS and PCI
      capable and non-PCI capable local hospitals, establishment of IRN-STEMI
      effectively increased the ratio of primary PCI for STEMI patients, it also
      significantly shortened the FMC-to-B and D-to-B time, decreased mean medical
      cost, thus, the regional IRN-STEMI network might be an effective working system
      for improving the medical care for STEMI patients.

PMID- 25388338
TI  - [Clinical characteristics and prognosis comparison of Chinese non ST-segment
      elevation acute coronary syndrome patients in two different time periods].
AB  - OBJECTIVE: To compare the clinical characteristics, treatment methods and
      outcomes in Chinese non ST-segment elevation acute coronary syndrome (NSTE-ACS)
      patients from two large clinical trials in different time periods. METHODS: All
      Chinese NSTE-ACS patients from two large International clinical trials (OASIS
      Registry and TIMACS) underwent coronary artery angiography after first admission
      were recruited in our analysis. The follow-up time was 180 days. A total of 1 473
      NSTE-ACS patients were recruited in this analysis, in which 749 from Organization
      to Assess Strategies for Ischemic Syndromes (OASIS REISTRY) that completed in 38
      centers in China from April 1999 to December 2000, and the rest 724 patients from
      The Timing of Intervention in Acute Coronary Syndromes (TIMACS) trial in 24
      centers in China performed from April 2007 to June 2008. RESULTS: Compared to
      OASIS patients, TIMACS group were older ((64.2 +/- 10.1) years old vs. (58.7 +/-
      10.2) years old) , and fewer male patients (66.3% (480/724) vs. 74.4% (557/749))
      , lower blood pressure at admission, and more histories of previous PCI (9.4%
      (68/724 vs. 6.4% (48/749)), stroke (8.8% (64/724) vs. 5.1% (38/749)) ,
      hypertension (62.8% (455/724) vs. 56.6% (424/749)) and diabetes (23.3% (169/724)
      vs. 16.2% (121/749)), lower histories of coronary artery disease (37.4% (271/724)
      vs. 59.1% (443/749)) and myocardial infarction (12.0% (87/724) vs. 27.6%
      (207/749)) (all P < 0.05). After admission, comparing to OASIS group, TIMACS
      patients had significant higher PCI proportion (74.9% (524/724) vs. 49.3%
      (369/749), P < 0.001). In addition, for secondary prevention, TIMACS patients had
      significant higher standard medication treatment proportion during
      hospitalization, at discharge and at 180 days follow up than OASIS group (P <
      0.05 for beta-blocker, ACEI/ARB and lipid lowering drugs) and higher compliance
      rate. The combined primary outcome event rate at 180 days was much lower in
      TIMACS than in OASIS patients (13.3% (96/724) vs. 25.2% (189/749), P < 0.001)
      mostly due to the reduction on the refractory angina (5.2% (38/724) vs. 22.6%
      (169/749), P < 0.001) . RESULTS: of COX regression model adjusted for baseline
      levels and treatment during hospitalization showed that the incidence rate of
      combination endpoint (HR = 0.39, 95% CI: 0.29-0.53, P < 0.001) and refractory
      ischemia/angina rehospitalization (HR = 0.17, 95% CI: 0.11-0.25, P < 0.001) were
      both lower in TIMACS patients than in OASIS patients. CONCLUSION: PCI procedure
      and secondary prevention medication administration are more often applied in
      TIMACS patients than in OASIS group, which is related to less integrated
      incidence of primary outcomes reflecting progress in Chinese medical care for non
      ST elevated acute coronary syndrome patients according to the updated guidelines.

PMID- 25388339
TI  - [Left ventricular radial and longitudinal systolic function derived from magnetic
      resonance imaging in hypertrophic cardiomyopathy patients].
AB  - OBJECTIVE: To evaluate the left ventricular (LV) radial and longitudinal systolic
      function in hypertrophic cardiomyopathy (HCM) patients by 3.0 T MR. METHODS:
      Sixteen HCM (HCM group) and twenty normal adults (normal group) were examined
      with fast imaging employing steady-state (FIESTA) acquisition sequence of cardiac
      MRI. LV ejection fraction (LVEF), longitudinal shortening (LS) and fractional
      shortening (FS) in three standard levels were measured to analyze LV radial and
      longitudinal systolic function. RESULTS: Asymmetric hypertrophy was detected in
      all HCM patients. The LVEF and FS were significantly higher while LS was
      significantly lower in HCM group than those in normal group (P < 0.05 or 0.01).
      FS at basal and middle levels were significantly higher in HCM group than in
      normal group (both P < 0.01). FS in apex level was similar in the two groups (P =
      0.057). Pearson correlation analysis showed that LS was negatively related with
      the number of hypertrophy segments in HCM patients (r = -0.537, P = 0.032). But
      there was no correlation between FS and the number of hypertrophy segments as
      well as FS and LS in HCM patients (r = -0.090, P = 0.739; r = 0.049, P = 0.856).
      CONCLUSION: The LV longitudinal systolic function was reduced but the LV radial
      systolic function remained unchanged in HCM patients, thus, LS changes could
      better reflect myocardial systolic function in HCM patients.

PMID- 25388340
TI  - [Role of cardiac magnetic resonance on predicting outcome in patients with
      hypertrophic obstructive cardiomyopathy undergoing percutaneous transluminal
      septal myocardial ablation].
AB  - OBJECTIVE: To investigate the predictive value of cardiac magnetic resonance
      (CMR) on outcome of patients with hypertrophic obstructive cardiomyopathy (HOCM)
      undergoing percutaneous transluminal septal myocardial ablation (PTSMA). METHODS:
      A total of 38 consecutive HOCM patients underwent CMR imaging before PTSMA in
      Fuwai hospital From March 2010 to September 2012 were included in this
      retrospective study. The efficacy was defined as >30 mmHg (1 mmHg = 0.133 kPa)
      reduction of echocardiography derived left ventricular outflow tract gradient
      (LVOTG) at 6 months post operation. The relationship between CMR imaging derived
      parameters and effect of PTSMA was analyzed. Receiver operating curve (ROC) was
      applied to assess the predicting effectiveness of related CMR parameters.
      RESULTS: The effective rate of PTSMA was 65.8% (25/38). The thickness of basal
      anterior wall (r = 0.505, P = 0.001), basal anteroseptal wall (0.500, P = 0.001)
      and the sum of the two segments (r = 0.656, P < 0.001) was positively correlated
      to the post-procedure reduction of LVOTG. The area under the ROC curve of the
      thickness of basal anterior wall, basal anteroseptal wall and the sum of the two
      segments was 0.806, 0.675 and 0.834, respectively. The sensitivity was 84.6% and
      specificity was 84.0% to predict the efficacy of PTSMA using the sum of left
      ventricular basal anterior wall and basal anteroseptal wall thickness 49.6 mm as
      cut-off value. CONCLUSIONS: LVOTG reduction post PTSMA positively correlates to
      pre-procedure left ventricular basal anterior wall, basal anteroseptal wall and
      the total thickness of these two segments in patients with HOCM. The total
      thickness of these two segments is a superior parameter for predicting efficacy
      of PTSMA in HOCM patients.

PMID- 25388341
TI  - [Resveratrol attenuates hypoxia-reperfusion injury induced rat myocardium
      microvascular endothelial cell dysfunction through upregulating PI3K/Akt/SVV
      pathways].
AB  - OBJECTIVE: To detect the role of surviving (SVV) in the protective effect of
      resveratrol against hypoxia/reperfusion injury (H/RI) of cardiac microvascular
      endothelial cells (CMECs). METHODS: CMECs isolated from the hearts of adult rats
      were exposed to hypoxia (94% N2, 5% CO2, 1% O2) for 2 h followed by 4 h
      reoxygenation (95% O2, 5% CO2). The cell proliferation of CMECs was measured by
      MTT assay and Transwell method was used to detect migration ability of CMEC, PI
      AnnexinV double staining and flow cytometry technique were employed to observe
      the apoptotic rate of CMECs. The SVV protein expression was detected with Western
      blot method. RESULTS: Compared to control group, the proliferation (0.19 +/- 0.03
      vs. 0.42 +/- 0.07, P < 0.01) and migration ((28 +/- 2)/5HPF vs. (50 +/- 3)/5 HPF,
      P < 0.01) abilities were impaired and the apoptosis index ((19.7 +/- 0.8)% vs.
      (5.4 +/- 0.3)%, (P < 0.05) of CMEC was increased after H/RI. The proliferation
      (0.36 +/- 0.07 vs. 0.19 +/- 0.03, P < 0.05) and migration ((55 +/- 3)/5HPF vs.
      (28 +/- 2)/5HPF, P < 0.05) abilities of CMEC were significantly improved while
      the apoptosis index ((9.6 +/- 0.7)% vs. (19.7 +/- 0.8)%, P < 0.05) was
      significantly decreased in H/RI+resveratrol group compared to H/RI group.SVV
      protein expression was also upregulated in H/RI+resveratrol group compared to
      H/RI group (P < 0.05). To further ascertain the role of SVV in the protective
      effects of resveratrol, PI3K specific inhibitor LY294002 was added to
      H/RI+resveratrol group, the proliferation (0.25 +/- 0.05 vs. 0.36 +/- 0.07, P <
      0.05) and migration ((34 +/- 3)/5HPF vs. (55 +/- 3)/5HPF, P < 0.05) abilities
      were significantly decreased, the apoptosis index ((16.2 +/- 0.6)% vs. (9.6 +/-
      0.7)%, P < 0.05) was increased and the protein expression of SVV was
      downregulated (P < 0.05) in LY294002+H/RI+resveratrol group compared to
      H/RI+resveratrol group. CONCLUSION: Resveratrol could significantly reduce H/RI
      induced apoptosis and attenuate H/RI induced cardiac microvascular endothelial
      cells dysfunction through up-regulating PI3K/Akt/SVV pathways.

PMID- 25388342
TI  - [Electrophysiological study on the antiarrhythmic mechanism of ampelopsin in
      rats].
AB  - OBJECTIVE: To explore the antiarrhythmic mechanism of ampelopsin through
      electrophysiological study in rats. METHODS: The in vivo experimental groups were
      as follows:control group, low-dose, middle-dose and high-dose group. Arrhythmia
      in rats was induced by aconitine injection, and then the antiarrhythmic effects
      of ampelopsin were studied. Cardiomyocytes were isolated from rats therafter. The
      whole-cell patch-clamp technique was used to record action potential duration
      (APD), sodium currents (INa), calcium current (ICa), transient outward potassium
      currents (Ito) and inward rectifier potassium currents (IK1) in cardiomyocytes.
      RESULTS: In vivo experiments showed that the incidence of aconitine-induced
      experimental arrhythmias in low, middle and high-dose ampelopsin group was
      significantly lower than that in control group (n = 5 each group, all P < 0.05).
      In vitro whole-cell patch clamp experiments showed that action potential duration
      in low, middle and high-dose groups was significantly shorter than that in
      control group, and amplitude of action potential was also significantly lower in
      low, middle and high-dose ampelopsin groups than in control group (134.1 +/-
      6.9), (120.1 +/- 7.4), (113.2 +/- 9.0), and (101.8 +/- 5.1) mV for control, low,
      middle and high-dose group (n = 9 each group, all P < 0.05).Further research
      revealed that sodium currents in cardiomyocytes were decreased by low, middle and
      high-dose ampelopsin from (-36.75 +/- 3.60) to (-31.03 +/- 2.61), (-26.63 +/-
      3.72), and (-17.55 +/- 4.43) pA/pF (n = 9 each group, all P < 0.05), but the
      activation voltage for peak potential was not affected by ampelopsin. Moreover,
      the inward rectifier potassium current was also higher in high-dose ampelopsin
      group than in control group (P < 0.05). Calcium current and transient outward
      potassium current were similar among four groups. CONCLUSION: Ampelopsin exerts
      anti-arrhythmic effects in this rat model, and the underlying
      electrophysiological mechanism is partly associated with the inhibition of INa
      and enhancement of IK1, and prolongation of APD.

PMID- 25388343
TI  - [Selectively stimulating beta1-adrenergic receptor attenuates rat myocardial
      ischemia/reperfusion injury in vivo by inhibiting high mobility group box 1
      protein release].
AB  - OBJECTIVE: To investigate whether selectively stimulating beta1-adrenergic
      receptor could inhibit high mobility group box 1 protein and attenuate myocardial
      ischemia/reperfusion(I/R) injury in rats. METHODS: Eighty healthy male Sprague
      Dawley (SD) rats were randomly divided into seven groups: (1) Sham operated group
      (SO); (2) Ischemia/reperfusion (I/R) group; (3) Dobutamine1 (5 ug*kg-1 . min-1) +
      I/R group; (4) Dobutamine2 (10 ug.kg-1 * min-1) + I/R group; (5) LY294002 (0.3
      mg/kg) + Dobutamine2 + I/R group; (6) SB203580 (1 mg/kg) + Dobutamine2 + I/R
      group; (7) ZnPPIX (10 mg/kg) + Dobutamine2+I/R group. Rats were pretreated by
      saline, dobutamine, LY294002, SB203580 and ZnPPIX, respectively, then underwent
      myocardial I/R. Myocardial I/R injury and oxidative stress were assessed, and
      myocardial HO-1, NF-kappaB and HMGB1 expressions were measured by Western blot
      analysis. RESULTS: Dobutamine significantly reduced the myocardial infarct size
      (P < 0.05), myocardial enzymes (LDH and CK) (P < 0.05) and proinfiammation
      cytokines (TNF-alpha and IL-6), reduced oxidative stress (MDA and SOD) in a dose
      dependent manner (all P < 0.05). Meanwhile, dobutamine significantly and dose
      dependently mediated the induction of HO-1 (P < 0.05), the expression of NF
      kappaB (P < 0.05) and HMGB1 (P < 0.05). However, all the effects could be
      significantly reversed by co-treatment with LY294002, SB203580 and ZnPPIX (all P
      < 0.05). CONCLUSIONS: Current study demonstrates that selectively stimulating
      beta1-adrenergic receptor by dobutasmine could reduce rat myocardial I/R injury
      in vivo through promoting the induction of HO-1 and inhibiting HMGB1 release.

PMID- 25388344
TI  - [Relationship between resting heart rate and brachial-ankle pulse wave velocity
      in healthy Chinese population].
AB  - OBJECTIVE: To investigate the relationship between resting heart rate (RHR) and
      brachial-ankle pulse wave velocity (baPWV) in healthy Chinese population.
      METHODS: This was a retrospective cohort study, and a total of 5 852 participants
      were selected with stratified random sampling from the 101 510 workers of
      Tangshan Kailuan company who received the health examination during 2010-2011
      including epidemiological investigation, biochemical indicators measurement and
      baPWV measurement. A total of 5 440 participants met the inclusion criteria (aged
      40 years or older, without stroke, transient ischemic attack and myocardial
      infarction) and 5 153 participants (3 110 males, mean age (55.1 +/- 11.8) years
      old) with integral data were finally recruited into the final analysis. The
      observation population was divided into four groups according to RHR collected
      during health examinations:quartile 1 (RHR <= 63 beats/min, n = 1 405); quartile
      2 (63 beats/min < RHR <= 69 beats/min, n = 1 176); quartile 3 (69 beats/min < RHR
      <= 76 beats/min, n = 1 322); quartile 4 (RHR > 76 beats/min, n = 1 250).
      Multivariate logistic regression analysis was used to analyze the relationship
      between RHR and baPWV. RESULTS: (1) The mean baPWV was (1 586 +/- 400) cm/s, and
      the detection rates of baPWV >= 1 400 cm/s was 61.8% (3 185/5 153). (2) The baPWV
      of quartile 1, 2, 3 and 4 were (1 511 +/- 338) cm/s, (1 533 +/- 329) cm/s, (1 574
      +/- 368) cm/s and (1 734 +/- 462) cm/s, respectively, and the detection rates of
      baPWV >= 1 400 cm/s were 54.7% (769/1 405) , 56.0% (658/1 176), 63.1% (834/1 322)
      and 74.3% (929/1 150) , respectively. (3) Multiple logistic regression analysis
      showed that the detection rates of baPWV were significantly higher in quartile 2,
      3 and 4 compared to quartile 1, and the OR values were 1.37 (95% CI: 1.11-1.69),
      1.96 (95% CI: 1.59-2.41) and 2.60 (95% CI: 2.07-3.25), respectively, after
      adjusting for age, gender and systolic blood pressure, body mass index, fasting
      blood glucose, triglyceride, total cholesterol, high density lipoprotein
      cholesterol, hs-CRP, antihypertensive agents, smoking and exercise status.
      CONCLUSION: RHR is positively associated with baPWV in healthy Chinese
      population.

PMID- 25388345
TI  - [Meta-analysis of long-term outcomes of percutaneous coronary intervention or
      coronary artery bypass graft surgery in coronary artery disease patients with
      multi-vessel and/or left main stem disease].
AB  - OBJECTIVE: To evaluate the long-term outcomes of coronary artery disease patients
      with left main stem and/or multi-vessel disease receiving percutaneous coronary
      intervention (PCI) or coronary artery bypass graft(CABG). METHODS: PubMed,
      EMBase, Cochrane central register of controlled trials were searched to identify
      randomized controlled trials concerning the long-term outcomes of PCI and CABG in
      coronary artery disease patients with left main stem and/or multi-vessel disease
      before May 2013.Keywords included "angioplasty", "coronary", "coronary artery
      bypass surgery" and "stent". The data were analyzed by STATA 12.0. RESULTS: Six
      randomized controlled trials (5 071 patients) were enrolled for analyses.Five
      years all-cause mortality (RR = 1.13, 95% CI: 0.88-1.44, P = 0.35), incidence of
      myocardial infarction (RR = 1.20, 95% CI: 0.69-2.07, P = 0.53), and angina (RR =
      1.17, 95% CI: 0.88-1.57, P = 0.28) were similar between PCI and CABG groups.
      Major adverse cardiac and cerebrovascular event (RR = 1.85, 95% CI: 1.38-2.48, P
      < 0.01) and repeat revascularization (RR = 3.48, 95% CI: 2.20-5.53, P < 0.01)
      were significantly higher in PCI compared to CABG. CONCLUSIONS: The present
      analysis suggests that 5 years all-cause mortality is similar between PCI and
      CABG strategies.However, PCI is associated with higher major adverse cardiac and
      cerebrovascular event and repeat revascularization rate compared to CABG in
      patients with unprotected left main stem and/or multi-vessel disease.

PMID- 25388346
TI  - [A case report of cardiac angiosarcoma presented with recurrent pericardial
      effusion and cardiac tamponade].

PMID- 25388347
TI  - [A case of polymyositis with myocardial involvement].

PMID- 25388348
TI  - [A case of sinus arrest right after exercise].

PMID- 25388349
TI  - [Wearable cardioverter-defibrillator use in patients after myocardial
      infarction].

PMID- 25388350
TI  - [Research progress on relationship between early menopause and coronary artery
      disease in women].

PMID- 25388351
TI  - [Update on the protective effects of thioredoxin in cardiovascular diseases].

PMID- 25388352
TI  - Characteristics of IgA nephropathy in advanced-age patients.
AB  - PURPOSE: The susceptible age for IgA nephropathy (IgAN) is <30 years. However,
      IgAN sometimes develops in people aged >60 years, and its characteristics remain
      unknown. METHODS: We divided 600 IgAN patients into three groups: advanced-age
      group (AAG, n=31, >=60 years); middle-aged group (MAG, n=162, 40-59 years); and
      young-aged group (YAG, n=407, 20-39 years). We analyzed clinical and histological
      background, renal outcome, and risk of progression. RESULTS: In the AAG, mean
      arterial pressure (MAP) and the number of hypertensive patients were
      significantly higher than in the YAG. Total protein, serum albumin, and estimated
      glomerular filtration rate were significantly lower, and blood urea nitrogen,
      proteinuria, and N-acetyl-beta-D-glucosaminidase were significantly higher in the
      AAG than in MAG and YAG. In histological findings, interstitial fibrosis/tubular
      atrophy by Oxford classification and arteriosclerosis were more severe in the AAG
      than the in YAG. Renal survival rate analyzed by Kaplan-Meier method was
      significantly lower in the AAG (22.9%/19 years in the AAG vs. 69.2 and 84.9%/20
      years in the MAG and YAG, p<0.0001). The patients who progressed to end-stage
      renal disease (ESRD) in the AAG had higher MAP and more severe proteinuria
      compared with the patients who did not progress to ESRD in the AAG. CONCLUSIONS:
      The characteristics of IgAN in advanced-age were lower renal function, high
      levels of proteinuria, severe interstitial change, and arteriolosclerosis caused
      by glomerulopathy and concomitant diseases, such as hypertension, dyslipidemia,
      and hyperuricemia. Prognosis was poor, and >70% developed ESRD within 20 years.

PMID- 25388353
TI  - Snail is an independent prognostic indicator for predicting recurrence and
      progression in non-muscle-invasive bladder cancer.
AB  - OBJECTIVE: Snail, an inducer of the epithelial-to-mesenchymal transition,
      increases motility and invasiveness of cancer cells by repressing E-cadherin
      expression. We investigate the relationship between Snail expression and
      clinicopathological parameters and evaluate its prognostic significance in
      patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS:
      A total of 332 patients treated with transurethral resection of the bladder tumor
      between October 2002 and July 2010 were histopathologically confirmed to be
      NMIBC. Tumor recurrence and progression were followed up in all patients.
      Immunohistochemical staining of 332 slices was performed. The expression of Snail
      was evaluated by ICH and graded for intensity and area of staining. We correlated
      Snail scores with clinical and pathological variables, and association of Snail
      staining with tumor recurrence and progression was evaluated by univariate,
      multivariate analysis and Kaplan-Meier survival curves. RESULTS: Of 332 patients
      with NMIBC, there was Snail positivity in 104 tumors (31.3 %), and Snail
      expression correlated with age, multifocality, carcinoma in situ, tumor stage and
      tumor grade (each p < 0.05, respectively). A multivariate Cox regression model
      revealed that Snail expression was an independent predictor of tumor recurrence
      [hazard ratio (HR) 1.95, p = 0.001] and progression (HR 2.34, p = 0.014) in
      patients with NMIBC. Kaplan-Meier estimates showed that Snail expression was
      significantly associated with recurrence and progression (log-rank test, p <
      0.0001, respectively). CONCLUSIONS: Analysis of Snail expression in 332 NMIBC
      tissue specimens revealed its potential usefulness as a biomarker to predict the
      NMIBC prognosis.

PMID- 25388355
TI  - Magnetic and transport properties of epitaxial thin film MgFe2O4 grown on MgO
      (100) by molecular beam epitaxy.
AB  - Magnesium ferrite is a very important magnetic material due to its interesting
      magnetic and electrical properties and its chemical and thermal stability. Here
      we report on the magnetic and transport properties of epitaxial MgFe2O4 thin
      films grown on MgO (001) by molecular beam epitaxy. The structural properties and
      chemical composition of the MgFe2O4 films were characterized by X-Ray diffraction
      and X-Ray photoelectron spectroscopy, respectively. The nonsaturation of the
      magnetization in high magnetic fields observed for M (H) measurements and the
      linear negative magnetoresistance (MR) curves indicate the presence of anti-phase
      boundaries (APBs) in MgFe2O4. The presence of APBs was confirmed by transmission
      electron microscopy. Moreover, post annealing decreases the resistance and
      enhances the MR of the film, suggesting migration of the APBs. Our results may be
      valuable for the application of MgFe2O4 in spintronics. 

PMID- 25388354
TI  - Sources of variation in assessing left atrial functions by 2D speckle-tracking
      echocardiography.
AB  - Left atrial (LA) strain and strain rate, determined by speckle-tracking
      echocardiography (STE), are reproducible indices to assess LA function. Different
      normal ranges for LA phasic functions have been reported. We investigated the
      role of the reference point (P- and R-wave), gain, and region of interest (ROI),
      as the major sources of variation when assessing LA function. 52 subjects were
      evaluated for LA conventional and STE analysis. 45 of them (46 +/- 14 years, 26
      men) were feasible for concomitant LA deformation, and LA phasic volumes and
      ejection fractions (LAEF) evaluation. First, we compared the P- and R-wave
      methods, for the evaluation of the LA functions. We used diastolic mitral profile
      to clearly delineate the time intervals for each LA function. For the P-wave
      method, active function was assessed from negative global strain as a difference
      between the strain at pre-atrial contraction and strain just before mitral valve
      closure (GSA-), and late diastolic strain rate (GSRL); passive function from
      positive strain at MVO (GSA+), and from early negative diastolic strain rate
      (GSRE); reservoir function from the sum of GSA- and GSA+ (TGSA), and positive
      strain rate at the beginning of LV systole (GSR+). For the R-wave method we used
      the same SR parameters. The active function was evaluated by late positive global
      strain (GSAC), the reservoir by positive peak before the opening of the mitral
      valve (TGSA), and conduit function by the difference between TGSA and GSAC
      (GSA+). Then, by using P-wave method, we measured all previously described
      parameters for different gains-minimum (G0), medium (G12), and maximum (G24), and
      for different ROIs-minimum (ROI0), step 1 (ROI1), and 2 (ROI2). Feasibility of
      the LA strain measurements was 87 %. Active LA function was similar in the
      absolute value (GSAC and GSA-), whereas passive and reservoir functions were
      significantly higher (GSA+, TGSA) with the R-wave method. Active LAEF correlated
      with GSA- measured by the P-wave (r = -0.44, p = 0.002), but not with the GSAC
      measured by the R-wave method. Similar correlations were found for passive and
      reservoir LAEF with correspondent strain parameters, only with P-wave method.
      There were no differences between methods regarding SR indices and their
      correlations with correspondent LAEFs. Increase of gain from minimum to maximum
      overestimated all measured LA functions (all p < 0.05). Intermediary changes did
      not have a significant impact on the measurement of active and conduit function,
      but they do have on the measurement of the reservoir function. Increase of ROI
      from minimum to ROI2 was associated with an overestimation of all measurements of
      atrial functions (all p < 0.05). For all parameters, except GSR+, a decrease of
      atrial S and SR values from minimum ROI to step 1 was recorded. For GSA+, TGSA,
      GSRE a decrease of S and SR values with each ROI step was recorded. The two
      methods used to assess LA functions by STE do not provide similar results. The R
      wave method essentially ignores negative peak, creating a positive strain for
      atrial contraction, and also provides higher values for the reservoir and conduit
      functions, by comparison with the P-wave method. Increase of gain overestimates,
      whereas increase of ROI underestimates all parameters of LA functions. Therefore,
      we suggest that P-wave as a reference point, a medium gain, and a minimum ROI
      should be used as the best choice for a correct assessment.

PMID- 25388356
TI  - Reference ranges of Doppler parameters of foetal pulmonary artery segments
      between 19 and 39 weeks of gestation.
AB  - OBJECTIVE: To determine reference ranges of Doppler parameters of foetal
      pulmonary artery segments. METHODS: A prospective cross-sectional study was
      conducted to evaluate 150 healthy singleton pregnancies between 19 and 39 weeks
      of gestation. The proximal, middle and distal segments of the foetal pulmonary
      artery were assessed. The following Doppler parameters were evaluated:
      pulsatility index (PI) and peak systolic velocity (PSV). The mean, standard
      deviation (SD) and maximum and minimum values were determined for each Doppler
      parameter. Pearson's correlation coefficient (r) was used to assess the
      correlation between the foetal pulmonary artery segments. Polynomial regression
      was performed, and adjustments were made using the coefficient of determination
      (R(2)). RESULTS: The mean PI values (mean +/- SD) in the proximal, middle and
      distal arterial segments were 2.99 +/- 0.61, 2.25 +/- 0.96 and 1.31 +/- 0.58,
      respectively. The mean PSVs in the proximal, middle and distal segments were
      50.68 +/- 16.63, 24.396 +/- 11.86 and 12.08 +/- 3.66 cm/s, respectively.
      Significant differences were observed between the PI and PSV values from the
      different segments (p < 0.0001). A correlation between each Doppler parameter and
      gestational age was observed, and it was better represented using linear
      equations. CONCLUSION: We successfully determined the reference ranges for
      Doppler parameters of foetal pulmonary artery segments between 19 and 39 weeks of
      gestation.

PMID- 25388357
TI  - Evaluation of inflammatory mediators in the deciduas of pregnant women with pre
      eclampsia/eclampsia.
AB  - OBJECTIVE: The objective was to evaluate some inflammatory mediators, i.e.
      cytokines that induce and inhibit nitric oxide (NO) synthase, in pregnant women
      with pre-eclampsia/eclampsia (PE/E) compared to clinically normal patients.
      METHODS: Placental fragments were collected from 46 pregnant patients, including
      30 clinically normal subjects and 16 women with PE/E, and stored in NP40
      containing phosphate buffer in a freezer at -70  degrees C until the time of
      solubilization. Cytokines IL-4, IL-10, IL-13, TNF-alpha and IFN-gamma were
      assayed by ELISA and NO was estimated by the Griess reaction after reduction.
      RESULTS: Patients with PE/E presented significantly lower placental levels of IL
      10 and IL-3 than the control group (p < 0.05). On the other hand, IL-4, TNF-alpha
      and IFN-gamma levels were similar on the two groups, whereas nitrite/nitrate
      levels were significantly lower in the PE/E group. A higher inflammatory balance
      was observed in patients with PE/E compared to normal subjects (p < 0.05).
      CONCLUSION: Patients with PE/E present lower levels of Th2 cytokines associated
      with a pro-inflammatory balance as evaluated by the IL-10/TNF-alpha ratio, as
      well as lower nitrite/nitrate levels, than controls.

PMID- 25388359
TI  - Commentary: research highlights: IKKbeta mediates Abeta-triggered microglial
      inflammation and neuronal death during Alzheimer's disease.

PMID- 25388360
TI  - Linkage of neurodegenerative disorders with other health issues--volume II.

PMID- 25388361
TI  - Hidden aspects of the Structural theory of chemistry: MC-QTAIM analysis reveals
      "alchemical" transformation from a triatomic to a diatomic structure.
AB  - The Structural theory of chemistry introduces chemical/molecular structure as a
      combination of relative arrangement and bonding patterns of atoms in a molecule.
      Nowadays, the structure of atoms in molecules is derived from the topological
      analysis of the quantum theory of atoms in molecules (QTAIM). In this context, a
      molecular structure is varied by large geometrical variations and concomitant
      reorganization of electronic structure that usually take place in chemical
      reactions or under extreme hydrostatic pressure. In this report, a new mode of
      structural variation is introduced within the context of the newly proposed multi
      component QTAIM (MC-QTAIM) that originates from the mass variation of nuclei.
      Accordingly, XCN and CNX series of species are introduced where X stands for a
      quantum particle with a unit of positive charge and a variable mass that is
      varied in discrete steps between the mass of a proton and a positron. Ab initio
      non-Born-Oppenheimer (non-BO) calculations are done on both series of species and
      the resulting non-BO wavefunctions are used for the MC-QTAIM analysis, revealing
      a triatomic structure for the proton mass and a diatomic structure for the
      positron mass. In both series of species, a critical mass between that of proton
      and positron mass is discovered where the transition from triatomic to diatomic
      structure takes place. This abrupt structural transformation has a topological
      nature resembling the usual phase transitions in thermodynamics. The discovered
      mass-induced structural transformation is a hidden aspect of the Structural
      theory which is revealed only beyond the BO paradigm, when nuclei are treated as
      quantum waves instead of clamped point charges. 

PMID- 25388362
TI  - Theoretical study of xenon adsorption in UO2 nanoporous matrices.
AB  - We present a theoretical study of xenon incorporation in UO2 nanocavities, by
      means of Grand Canonical Monte Carlo calculations based on semi-empirical
      potentials. We first characterize the reconstruction of the matrix around an
      empty cavity which leads to a stoechiometry change from UO2 to UO in this region.
      Then, we determine xenon adsorption isotherms which exhibit an abrupt transition
      from a dilute phase to a dense one and an increase in the density of the latter
      phase as a function of temperature. This last result is attributed to a
      vibrational entropy effect by means of a mean field analysis. Finally, the
      pressure calculation inside the bubble proves the limitations of the usual
      mesoscopic models based on gas state behaviour.

PMID- 25388363
TI  - Integrated metabolomic and proteomic analysis reveals systemic responses of
      Rubrivivax benzoatilyticus JA2 to aniline stress.
AB  - Aromatic amines are widely distributed in the environment and are major
      environmental pollutants. Although degradation of aromatic amines is well studied
      in bacteria, physiological adaptations and stress response to these toxic
      compounds is not yet fully understood. In the present study, systemic responses
      of Rubrivivax benzoatilyticus JA2 to aniline stress were deciphered using
      metabolite and iTRAQ-labeled protein profiling. Strain JA2 tolerated high
      concentrations of aniline (30 mM) with trace amounts of aniline being transformed
      to acetanilide. GC-MS metabolite profiling revealed aniline stress phenotype
      wherein amino acid, carbohydrate, fatty acid, nitrogen metabolisms, and TCA
      (tricarboxylic acid cycle) were modulated. Strain JA2 responded to aniline by
      remodeling the proteome, and cellular functions, such as signaling,
      transcription, translation, stress tolerance, transport and carbohydrate
      metabolism, were highly modulated. Key adaptive responses, such as
      transcription/translational changes, molecular chaperones to control protein
      folding, and efflux pumps implicated in solvent extrusion, were induced in
      response to aniline stress. Proteo-metabolomics indicated extensive rewiring of
      metabolism to aniline. TCA cycle and amino acid catabolism were down-regulated
      while gluconeogenesis and pentose phosphate pathways were up-regulated, leading
      to the synthesis of extracellular polymeric substances. Furthermore, increased
      saturated fatty acid ratios in membranes due to aniline stress suggest membrane
      adaptation. The present study thus indicates that strain JA2 employs multilayered
      responses: stress response, toxic compound tolerance, energy conservation, and
      metabolic rearrangements to aniline. 

PMID- 25388364
TI  - IMAGING DIAGNOSIS-SPONTANEOUS PNEUMOMEDIASTINUM SECONDARY TO PRIMARY PULMONARY
      PATHOLOGY IN A DALMATIAN DOG.
AB  - A 1.5-year-old, 23 kg intact male Dalmatian dog was evaluated for acute
      respiratory insufficiency without a previous history of trauma or toxic
      exposition. Imaging revealed pneumomediastinum, pneumothorax, diffuse
      unstructured interstitial pulmonary pattern, pulmonary interstitial emphysema,
      and pneumoretroperitoneum. Histopathological evaluation of the lungs revealed
      perivascular and peribronchial emphysema, mild lymphocytic interstitial pneumonia
      with atypical proliferation of type II pneumocytes in bronchioles and alveoli. A
      lung disease resembling fibrosing interstitial pneumonia in man and cats has been
      previously reported in Dalmatians and should be included as a differential
      diagnosis for Dalmatians with this combination of clinical and imaging
      characteristics. 

PMID- 25388366
TI  - Benign multicystic peritoneal mesothelioma: a rare cause of intra-abdominal
      cystic disease.

PMID- 25388365
TI  - Cross-sectional study of cytomegalovirus shedding and immunological markers among
      seropositive children and their mothers.
AB  - BACKGROUND: Congenital cytomegalovirus (CMV) is the leading infectious cause of
      birth defects in the United States. To better understand factors that may
      influence CMV transmission risk, we compared viral and immunological factors in
      healthy children and their mothers. METHODS: We screened for CMV IgG antibodies
      in a convenience sample of 161 children aged 0-47 months from the Atlanta,
      Georgia metropolitan area, along with 32 mothers of children who screened CMV
      seropositive. We assessed CMV shedding via PCR using saliva collected with oral
      swabs (children and mothers) and urine collected from diapers using filter paper
      inserts (children only). RESULTS: CMV IgG was present in 31% (50/161) of the
      children. Half (25/50) of seropositive children were shedding in at least one
      fluid. The proportion of seropositive children who shed in saliva was 100% (8/8)
      among the 4-12 month-olds, 64% (9/14) among 13-24 month-olds, and 40% (6/15)
      among 25-47 month-olds (P for trend=0.003). Seropositive mothers had a lower
      proportion of saliva shedding (21% [6/29]) than children (P<0.001). Among
      children who were shedding CMV, viral loads in saliva were significantly higher
      in younger children (P <0.001); on average, the saliva viral load of infants
      (i.e., <12 months) was approximately 300 times that of two year-olds (i.e., 24-35
      months). Median CMV viral loads were similar in children's saliva and urine but
      were 10-50 times higher (P<0.001) than the median viral load of the mothers'
      saliva. However, very high viral loads (> one million copies/mL) were only found
      in children's saliva (31% of those shedding); children's urine and mothers'
      saliva specimens all had fewer than 100,000 copies/mL. Low IgG avidity, a marker
      of primary infection, was associated with younger age (p=0.03), higher viral
      loads in saliva (p=0.02), and lower antibody titers (p=0.005). CONCLUSIONS: Young
      CMV seropositive children, especially those less than one year-old may present
      high-risk CMV exposures to pregnant women, especially via saliva, though further
      research is needed to see if this finding can be generalized across racial or
      other demographic strata.

PMID- 25388367
TI  - Cholesteatoma risk in 8,593 orofacial cleft cases and 6,989 siblings: A
      nationwide study.
AB  - OBJECTIVES/HYPOTHESIS: To estimate the risk of surgically treated middle ear
      cholesteatoma in individuals with a nonsyndromic orofacial cleft and in their
      siblings compared with the general population. STUDY DESIGN: Historical cohort
      study. METHODS: Using the unique civil registration number for linkage, data from
      three national registers were used for the Danish 1936-2009 birth cohorts. Hazard
      ratios (HRs) were estimated with Cox regression analyses using age as the
      underlying time variable. Individuals were followed from January 1, 1977 until
      time of surgically treated cholesteatoma, and censored at emigration, death, or
      end of follow-up (December 31, 2010). RESULTS: A total of 8,593 individuals with
      nonsyndromic orofacial cleft and 6,989 siblings were identified, undergoing 201
      and 21 first-time cholesteatoma surgeries, respectively. A 5% random sample of
      the Danish population comprising 249,708 persons without an orofacial cleft was
      created, and 175,724 siblings to these persons were identified. These controls
      underwent 485 and 332 first-time cholesteatoma surgeries, respectively. For
      individuals with cleft lip and palate the HR for cholesteatoma surgery was 14
      (95% confidence interval [CI], 12-18) and for individuals with cleft palate the
      HR was 20 (95% CI, 16-24) when compared with the random sample. In siblings of
      individuals with cleft palate, the HR for cholesteatoma surgery was 2.1 (95% CI,
      1.1-4.1) when compared with siblings of the random sample. CONCLUSIONS: A 20-fold
      increase in the risk of cholesteatoma was found in individuals with cleft palate,
      whereas cleft lip did not pose a risk of cholesteatoma. Furthermore, the study
      indicates an increased risk of cholesteatoma in unaffected siblings of
      individuals with cleft palate. LEVEL OF EVIDENCE: 2b Laryngoscope, 125:1225-1229,
      2015.

PMID- 25388368
TI  - Probing the involvement of the earliest levels of cortical processing in motion
      extrapolation with rapid forms of visual motion priming and adaptation.
AB  - In this study, we investigated the effect of brief motion priming and adaptation,
      occurring at the earliest levels of the cortical visual stream, on time-to
      contact (TTC) estimation of a target passing behind an occluder. By using
      different exposure times of directional motion presented in the occluder area
      prior to the target's disappearance behind it, our aim was to modulate (prime or
      adapt) the extrapolated motion of the invisible target, thus producing different
      TTC estimates. Our results showed that longer (yet subsecond) exposures to motion
      in the same direction as the target produced late TTC estimates, whereas shorter
      exposures produced shorter TTC estimates, indicating that rapid forms of motion
      adaptation and motion priming affect extrapolated motion. Our findings suggest
      that motion extrapolation might occur at the earliest levels of cortical
      processing of motion, at which these rapid mechanisms of priming and adaptation
      take place. 

PMID- 25388369
TI  - Specific and unspecific gynecological alarm symptoms--prevalence estimates in
      different age groups: a population-based study.
AB  - OBJECTIVE: To determine prevalence estimates of gynecological alarm symptoms in
      different age groups and to describe common patterns of gynecological symptoms.
      DESIGN: Web-based cross-sectional survey study. SETTING: Nationwide in Denmark.
      POPULATION: A random sample of 51,090 women aged 20 years or above from the
      general population. METHODS: An internet-based questionnaire study regarding the
      prevalence estimates of symptom experiences. A total of 18 symptoms of cervical,
      endometrial and ovarian cancer were selected through an extensive literature
      search, which included national and international guidelines. MAIN OUTCOME
      MEASURES: Prevalence estimates of self-reported experience of gynecological alarm
      symptoms within the preceding 4 weeks. RESULTS: A total of 26,466 women (54.5%)
      participated in the study. Some 80.3% had experienced at least one of the alarm
      symptoms within the preceding 4 weeks, and the median number of experienced
      symptoms was 2 (interquartile range 1-4). The most common symptoms were tiredness
      (53.0%) and abdominal bloating (36.7%); postmenopausal bleeding (2.3%) and
      involuntary weight loss (2.8%) were least frequent. Most of the symptoms were
      more prevalent among younger women, whereas only dyspnea and increased urgency of
      urination were more frequent among older women. Among younger women, multiple
      abdominal symptoms often occurred simultaneously and frequently in combination
      with pelvic pain, whereas older women were more likely to report single symptoms.
      CONCLUSIONS: Gynecological alarm symptoms are frequent in the general population,
      mostly among younger women. Older women reported fewer symptoms, and these often
      appeared as single symptoms.

PMID- 25388370
TI  - The "Skinny" on brown fat, obesity, and bone.
AB  - The discovery that metabolically active brown fat is present in humans throughout
      ontogeny raises new questions about the interactions between thermoregulatory,
      metabolic, and skeletal homeostasis. Brown adipose tissue (BAT) is distinct from
      white adipose tissue (WAT) for its ability to burn, rather than store, energy.
      BAT uniquely expresses uncoupling protein-1 (abbreviated as UCP1), which diverts
      the energy produced by cellular respiration to generate heat. While BAT is found
      in small mammals, hibernators, and newborns, this depot was thought to regress in
      humans during early postnatal life. Recent studies revealed that human BAT
      remains metabolically active throughout childhood and even in adulthood,
      particularly in response to cold exposure. In addition to the constitutive BAT
      depots present at birth, BAT cells can be induced within WAT depots under
      specific metabolic and climatic conditions. These cells, called inducible brown
      fat, "brite," or beige fat, are currently the focus of intense investigation as a
      possible treatment for obesity. Inducible brown fat is associated with higher
      bone mineral density, suggesting that brown fat interacts with bone growth in
      previously unrecognized ways. Finally, BAT may have contributed to climatic
      adaptation in hominins. Here, I review current findings on the role of BAT in
      thermoregulation, bone growth, and metabolism, describe the potential role of BAT
      in moderating the obesity epidemic, and outline possible functions of BAT across
      hominin evolutionary history.

PMID- 25388371
TI  - Comparison of S-nitrosoglutathione- and staurosporine-induced apoptosis in human
      neural cells.
AB  - S-nitrosoglutathione (GSNO) is an endogenously produced S-nitrosylating compound
      that controls the function of various proteins. While a number of rodent cell
      lines have been used to study GSNO-induced apoptosis, the mechanisms of action
      remain to be evaluated in human cells and in parallel with other common apoptosis
      inducing agents. In this study, we compared the pro-apoptotic effects of GSNO and
      staurosporine (STS) on human neural progenitors (NT2, hNP1) and neuroblasts (SH
      SY5Y). We show that these cells exhibit comparable levels of susceptibility to
      GSNO- and STS-induced apoptotic cell death, as demonstrated by condensed nuclei
      and CASP3 activation. Mechanistic differences in apoptotic responses were
      observed as differential patterns of DNA fragmentation and levels of BAX, BCL-XL,
      CASP8, and p-ERK in response to GSNO and STS treatment. Mitochondrial membrane
      potential analysis revealed that NT2 and hNP1 cells, but not SH-SY5Y cells,
      undergo mitochondrial hyperpolarization in response to short-term exposure to STS
      prior to undergoing subsequent depolarization. This is the first study to report
      differences in apoptotic responses to GSNO and STS in 3 complementary human
      neural cell lines. Furthermore, these cells represent useful tools in cell
      pharmacological paradigms in which susceptibility to apoptosis-inducing agents
      needs to be assessed at different stages of neural cell fate commitment and
      differentiation. 

PMID- 25388372
TI  - Transcutaneous electrical nerve stimulation as an additional treatment for women
      suffering from therapy-resistant provoked vestibulodynia: a feasibility study.
AB  - INTRODUCTION: The current approach to women with provoked vestibulodynia (PVD)
      comprises a multidimensional, multidisciplinary therapeutic protocol. As PVD is
      considered to be a chronic pain disorder, transcutaneous electrical nerve
      stimulation (TENS) can be used as an additional therapy for women with otherwise
      therapy-resistant PVD. AIMS: The aims of this study were to evaluate whether TENS
      has a beneficial effect on vulvar pain, sexual functioning, and sexually-related
      personal distress in women with therapy-resistant PVD and to assess the effect of
      TENS on the need for vestibulectomy. METHODS: A longitudinal prospective follow
      up study was performed on women with therapy-resistant PVD who received
      additional domiciliary TENS. Self-report questionnaires and visual analog scales
      (VASs) were completed at baseline (T1), post-TENS (T2), and follow-up (T3). MAIN
      OUTCOME MEASURES: Vulvar pain, sexual functioning, and sexually-related personal
      distress were the main outcome measures. RESULTS: Thirty-nine women with therapy
      resistant PVD were included. Mean age was 27 +/- 5.6 years (range: 19 to 41);
      mean duration between TENS and T3 follow-up was 10.1 +/- 10.7 months (range: 2 to
      32). Vulvar pain VAS scores directly post-TENS (median 3.4) and at follow-up
      (median 3.2) were significantly (P < 0.01) lower than at baseline (median 8.0).
      Post-TENS, sexual functioning scores on the Female Sexual Functioning Index
      questionnaire had improved significantly (P = 0.2); these scores remained stable
      at follow-up. Sexually-related personal distress scores had improved
      significantly post-TENS (P = 0.01). Only 4% of the women who received TENS needed
      to undergo vestibulectomy vs. 23% in our previous patient population. CONCLUSION:
      The addition of self-administered TENS to multidimensional treatment
      significantly reduced the level of vulvar pain and the need for vestibulectomy.
      The long-term effect was stable. These results not only support our hypothesis
      that TENS constitutes a feasible and beneficial addition to multidimensional
      treatment for therapy-resistant PVD, but also the notion that PVD can be
      considered as a chronic pain syndrome.

PMID- 25388373
TI  - Inhibitors of BCR signalling interrupt the survival signal mediated by the micro
      environment in mantle cell lymphoma.
AB  - Several studies provide evidences for mantle cell lymphoma (MCL) cell survival
      relying on B-cell receptor (BCR)-mediated signalling pathways, whereas the nature
      of this activation is unknown. Significant progress in MCL treatment is achieved
      through therapies targeting BCR-associated kinases, i.e., Ibrutinib and
      Fostamatinib, inhibitors of BTK and SYK, respectively. Our study addresses
      survival signals emanating from the BCR or the tumour environment and how
      inhibiting BCR signalling effectors might impact these survival signals. We found
      that BTK was constitutively activated and that SYK phosphorylation was highly
      increased and sustained upon BCR activation of primary MCL cells. Moreover, MCL
      cells from leukaemic patients secreted high amount of IL-1beta, IL-6, IL-8 and
      CCL5. Activation of the BCR induced (i) cell survival, (ii) STAT3 activation and
      (iii) increased autocrine secretion of IL-1beta, IL-6, IL-8, CCL5, IL-10,
      TNFalpha and VEGF. Specific inhibition of BTK by Ibrutinib or SYK by Fostamatinib
      (R406) reversed these protective effects and decreased both basal and BCR-induced
      autocrine cytokine secretions associated with STAT3 phosphorylation.
      Interestingly, targeting BTK and SYK prevented and inhibited BCR-induced MCL cell
      adhesion to human bone marrow stromal cells (HMSCs) in short- and long-term co
      culture. We demonstrated that BCR-induced survival relies on autocrine secretion
      of IL-1beta, TNFalpha and CCL5 that might facilitate adhesion of MCL cells to
      HMSC. Treatment with Ibrutinib or Fostamatinib blocked the chemotactic signal
      thus increasing apoptosis. 

PMID- 25388374
TI  - Evaluation of the effect of nasal dorsal skin cooling on nasal mucosa by acoustic
      rhinometry.
AB  - BACKGROUND: The use of cold nasal packs on the nose and nape of the neck is
      currently recommended for patients with epistaxis as this is thought to induce
      reflex nasal vasoconstriction, which decreases the bleeding. There have been a
      few investigations on the effect of cold compress application to the nose, but
      none of these focused specifically on nasal cooling of the skin of the nose.
      METHODS: Acoustic rhinometry was performed to obtain baseline measurements. Nasal
      dorsal skin was then cooled with two ice packs that were held on the left and
      right side of the nose for a total of 10 minutes by the subjects. The rhinometry
      measurements were taken at the time of initial application (baseline), and after
      5 and 10 minutes of ice pack application. RESULTS: Comparisons of the first and
      second minimal cross-sectional area values, and total nasal cavity volume
      measurements revealed no statistical differences. CONCLUSION: The results of this
      study indicate that one should be sceptical about the efficiency of cold compress
      application, which is frequently used in clinical practice in cases with
      epistaxis.

PMID- 25388375
TI  - The Role of Social Connectedness and Sexual Orientation in the Prevention of
      Youth Suicide Ideation and Attempts Among Sexually Active Adolescents.
AB  - The impact of types of social connectedness-family, other adult, and school-on
      suicide ideation and attempts among all youth, the relative impact of each type,
      and effect modification by sexual orientation was assessed. Data were from the
      2007-2009 Milwaukee Youth Risk Behavior Surveys. Multivariable logistic
      regression analyses calculated the risk of suicide ideation and attempts by
      sexual orientation, types of social connectedness, and their interaction. Among
      all youth, each type of connectedness modeled singly conferred protective effects
      for suicide ideation. Family and other adult connectedness protected against
      suicide attempts. When modeled simultaneously, family connectedness protected
      against ideation and attempts. Sexual orientation modified the association
      between other adult connectedness and suicide ideation. Findings suggest that
      family connectedness confers the most consistent protection among all youth and
      sexual orientation does not generally modify the association between
      connectedness and suicidal behavior. 

PMID- 25388377
TI  - Prevalence of myasthenia gravis and associated autoantibodies in paraneoplastic
      pemphigus and their correlations with symptoms and prognosis.
AB  - BACKGROUND: Paraneoplastic pemphigus (PNP) involves multiple organs, but little
      is known about its neurological involvement. OBJECTIVES: To investigate the
      symptoms, prognosis and profiles of associated autoantibodies in myasthenia
      gravis (MG), and their correlations in patients with PNP. METHODS: Fifty-eight
      patients with PNP were assessed for myasthenic symptoms and laboratory evidence.
      Serum autoantibodies against acetylcholine receptor (AChR), acetylcholinesterase
      (AChE), titin, ryanodine receptor (RyR) and muscle-specific kinase (MuSK) were
      measured by enzyme-linked immunosorbent assay. Patients with pemphigus vulgaris
      (PV), pemphigus foliaceus (PF), connective tissue disease (CTD) and non-PNP MG
      (NP-MG), and healthy donors, served as controls. These autoantibodies in PNP were
      also compared in the presence or absence of dyspnoea or muscle weakness. Cox
      regression and log-rank tests were used for survival analysis. RESULTS: Overall
      39% of patients with PNP experienced muscle weakness, and 35% were diagnosed with
      MG. Moreover, 35% had positive anti-AChR and 28% had anti-AChE antibodies,
      similarly to NP-MG (33% and 17%, respectively, P > 0.05). However, both were
      negative in all patients with PV, PF and CTD and healthy donors (P < 0.005). No
      other antibodies showed significant differences among groups. Anti-AChR and anti
      AChE antibody levels were significantly increased in patients with PNP with
      dyspnoea, while anti-AChR, anti-titin and anti-RyR were significantly increased
      in patients with PNP with muscle weakness (P < 0.05). Nevertheless, levels and
      positive rates of these autoantibodies showed no significant differences between
      PNP with Castleman disease and thymoma. Although anti-AChE levels impacted
      survival duration (P  =  0.027, odds ratio 3.14), MG complications did not affect
      the overall survival percentage in PNP. CONCLUSIONS: MG is a complication of PNP.
      Anti-AChR and anti-AChE antibodies are prominent in patients with PNP, especially
      those with dyspnoea.

PMID- 25388376
TI  - Unencapsulated Streptococcus pneumoniae from conjunctivitis encode variant traits
      and belong to a distinct phylogenetic cluster.
AB  - Streptococcus pneumoniae, an inhabitant of the upper respiratory mucosa, causes
      respiratory and invasive infections as well as conjunctivitis. Strains that lack
      the capsule, a main virulence factor and the target of current vaccines, are
      often isolated from conjunctivitis cases. Here we perform a comparative genomic
      analysis of 271 strains of conjunctivitis-causing S. pneumoniae from 72 postal
      codes in the United States. We find that the vast majority of conjunctivitis
      strains are members of a distinct cluster of closely related unencapsulated
      strains. These strains possess divergent forms of pneumococcal virulence factors
      (such as CbpA and neuraminidases) that are not shared with other unencapsulated
      nasopharyngeal S. pneumoniae. They also possess putative adhesins that have not
      been described in encapsulated pneumococci. These findings suggest that the
      unencapsulated strains capable of causing conjunctivitis utilize a pathogenesis
      strategy substantially different from that described for S. pneumoniae at other
      infection sites. 

PMID- 25388378
TI  - Association between FABP2 Ala54Thr polymorphisms and type 2 diabetes mellitus
      risk: a HuGE Review and Meta-Analysis.
AB  - Many studies have examined the association between the FABP2 (rs1799883) Ala54Thr
      gene polymorphism and type 2 diabetes mellitus risk (T2DM) in various
      populations, but their results have been inconsistent. To assess this
      relationship more precisely, A HuGE review and meta-analysis were performed. The
      PubMed and CNKI database was searched for case-control studies published up to
      April 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence
      intervals (CI) were calculated. Ultimately, 13 studies, comprising 2020 T2DM
      cases and 2910 controls were included. Overall, for the Thr carriers (Ala/Thr and
      Thr/Thr) versus the wild-type homozygotes (Ala/Ala), the pooled OR was 1.18 (95%
      CI = 1.04-1.34, P = 0.062 for heterogeneity), for Thr/Thr versus Ala/Ala the
      pooled OR was 1.17 (95% CI = 1.05-1.41 P = 0.087 for heterogeneity). In the
      stratified analysis by ethnicity, the significantly risks were found among Asians
      but not Caucasians. This meta-analysis suggests that the FABP2 (rs1799883)
      Ala54Thr polymorphisms are associated with increased susceptibility to T2DM risk
      among Asians but not Caucasians.

PMID- 25388379
TI  - Low-dose CT-derived attenuation scan: One acquisition, more applications?

PMID- 25388381
TI  - Short primer in stem cell biology.

PMID- 25388380
TI  - Quantitative high-efficiency cadmium-zinc-telluride SPECT with dedicated parallel
      hole collimation system in obese patients: results of a multi-center study.
AB  - BACKGROUND: Obesity is a common source of artifact on conventional SPECT
      myocardial perfusion imaging (MPI). We evaluated image quality and diagnostic
      performance of high-efficiency (HE) cadmium-zinc-telluride parallel-hole SPECT
      MPI for coronary artery disease (CAD) in obese patients. METHODS AND RESULTS: 118
      consecutive obese patients at three centers (BMI 43.6 +/- 8.9 kg.m(-2), range 35
      79.7 kg.m(-2)) had upright/supine HE-SPECT and invasive coronary angiography > 6
      months (n = 67) or low likelihood of CAD (n = 51). Stress quantitative total
      perfusion deficit (TPD) for upright (U-TPD), supine (S-TPD), and combined
      acquisitions (C-TPD) was assessed. Image quality (IQ; 5 = excellent; < 3
      nondiagnostic) was compared among BMI 35-39.9 (n = 58), 40-44.9 (n = 24) and >=45
      (n = 36) groups. ROC curve area for CAD detection (>=50% stenosis) for U-TPD, S
      TPD, and C-TPD were 0.80, 0.80, and 0.87, respectively. Sensitivity/specificity
      was 82%/57% for U-TPD, 74%/71% for S-TPD, and 80%/82% for C-TPD. C-TPD had
      highest specificity (P = .02). C-TPD normalcy rate was higher than U-TPD (88% vs
      75%, P = .02). Mean IQ was similar among BMI 35-39.9, 40-44.9 and >=45 groups
      [4.6 vs 4.4 vs 4.5, respectively (P = .6)]. No patient had a nondiagnostic stress
      scan. CONCLUSIONS: In obese patients, HE-SPECT MPI with dedicated parallel-hole
      collimation demonstrated high image quality, normalcy rate, and diagnostic
      accuracy for CAD by quantitative analysis of combined upright/supine
      acquisitions.

PMID- 25388382
TI  - Measurement of hematopoietic stem cell proliferation, self-renewal, and expansion
      potential.
AB  - All stem cells exhibit the capacity and ability to proliferate. This is a
      fundamental property of stem cells, since it is required not only for self
      renewal, but also for expansion and the ability for stem cells to engraft in a
      patient. The capacity or potential for proliferation by stem cells defines their
      degree of primitives or stemness. This, in turn, is directly related to stem cell
      self-renewal. Using a highly sensitive, accurate, and reliable ATP
      bioluminescence signal detection system that can be multiplexed with other assay
      readouts, it has been possible to determine three stem cell parameters using a
      single assay. Using primitive hematopoietic bone marrow stem cells as an example,
      an in vitro protocol is described that incorporates initially culturing primitive
      stem cells to induce them into cell cycle, followed by a secondary re-plating
      step that demonstrates both self-renewal capability and expansion potential. 

PMID- 25388384
TI  - Measuring the potency of a stem cell therapeutic.
AB  - The potency of a drug is one of the most important parameters of a therapeutic.
      Besides providing the basis for manufacturing consistency and product stability,
      the potency can predict product failure or toxicity due to incorrect potency,
      provide release criteria, and the dose that will ensure that it can be used as
      intended. Recently, cellular therapeutics, in particular, stem cell therapy
      products, have being designated as "drugs" by regulatory agencies if they produce
      a systemic effect in the patient. Regulatory agencies are becoming increasingly
      stringent with respect to the manufacture, production, and testing of these
      products prior to being used in a patient. A clear understanding of what potency
      is and how it can be measured should help erase the misunderstandings and
      misconceptions that have accrued within the cellular therapy field. This protocol
      describes how the potency of hematopoietic stem cell therapy products is
      determined. The same principles apply to any proliferating stem cell therapeutic
      product. 

PMID- 25388383
TI  - Measuring the aging process in stem cells.
AB  - Stem cells persist in replenishing functional mature cells throughout life by
      self-renewal and multilineage differentiation. Hematopoietic stem cells (HSCs)
      are among the best-characterized and understood stem cells, and they are
      responsible for the life-long production of all lineages of blood cells. HSCs are
      a heterogeneous population containing lymphoid-biased, myeloid-biased, and
      balanced subsets. HSCs undergo age-associated phenotypic and functional changes,
      and the composition of the HSC pool alters with aging. HSCs and their lineage
      biased subfractions can be identified and analyzed by flow cytometry based on
      cell surface makers. Fluorescence-activated cell sorting (FACS) enables the
      isolation and purification of HSCs that greatly facilitates the mechanistic study
      of HSCs and their aging process at both cellular and molecular levels. The mouse
      model has been extensively used in HSC aging study. Bone marrow cells are
      isolated from young and old mice and stained with fluorescence-conjugated
      antibodies specific for differentiated and stem cells. HSCs are selected based on
      the negative expression of lineage markers and positive selection for several
      sets of stem cell markers. Lineage-biased HSCs can be further distinguished by
      the level of SLAM/CD150 expression and the extent of Hoechst efflux. 

PMID- 25388385
TI  - Culturing protocols for human multipotent adult stem cells.
AB  - Culture procedures are presented that support the initiation and controlled
      expansion of the multipotent adult progenitor cell (MAPC) population within the
      human bone marrow derived multipotent mesenchymal stromal cell compartment.
      Culture procedures or conditions and characterization assays that maintain and
      survey the distinctive primitive MAPC properties are discussed in the context of
      cell culturing platforms that facilitate controlled expansion of clinical grade
      human MAPC product to levels required for mid to late stage clinical testing. 

PMID- 25388386
TI  - Isolation of murine bone marrow scavenging sinusoidal endothelial cells.
AB  - The bone marrow (BM) is permeated with sinusoidal vessels lined with sinusoidal
      endothelial cells (SEC), which are crucial for BM physiology and hemopoietic stem
      cell (HSC) renewal. However, little is known about the characteristics or
      functional capacity of bone marrow sinusoidal endothelial cells (BMSEC). One
      significant barrier to the study of BMSEC is the lack of specific cell surface
      markers that can be used to isolate these cells. Nevertheless, BMSEC possess one
      exceptional property, namely, the ability to scavenge large amounts of soluble
      waste molecules such as advanced glycation end-products (AGE) and we have
      utilized this to label BMSEC for cell sorting and isolation. We describe the
      means to produce and fluorescently label AGE, its use as a functional in vivo
      marker of BMSEC and the isolation of these cells from murine BM using fluorescent
      activated cell separation (FACS). 

PMID- 25388387
TI  - Analysis of circadian rhythms in embryonic stem cells.
AB  - Recent attention on the early development of circadian rhythms has yielded
      several avenues of potential study regarding molecular and physiological rhythms
      in embryonic stem cells (ESCs) and their derivatives. While general guidelines of
      experimental design are-as always-applicable, there are certain idiosyncrasies
      with respect to experiments involving circadian rhythms that will be addressed.
      ESCs provide a number of challenges to the circadian biologist: growth rates are
      normally much higher than in established cell culture systems, the cells' innate
      drive towards differentiation and the lack of known synchronizing input pathways
      are a few examples. Some of these challenges can be addressed post hoc, such as
      normalization to total RNA or protein for transcript abundance studies. Most
      others, as outlined here, require special handling of the samples before and
      during experimentation in order to preserve any potential circadian oscillation
      that is present. Failure to do so may result in a disruption of endogenous
      oscillation(s) or, potentially worse, generation of an artificial oscillation
      that has no biological basis. This chapter begins with cultured ESCs, derived
      from primary blastocysts or in the form of cell lines, and outlines two methods
      of measuring circadian rhythms: the 2DG method of measuring glucose uptake
      (Sokoloff et al. J Neurochem 28:897-916, 1977) and real-time measurement of
      molecular rhythms using transgenic bioluminescence (Yoo et al. Proc Natl Acad Sci
      U S A 101:5339-5346, 2004). 

PMID- 25388388
TI  - Measuring stem cell circadian rhythm.
AB  - Circadian rhythms are biological rhythms that occur within a 24-h time cycle.
      Sleep is a prime example of a circadian rhythm and with it melatonin production.
      Stem cell systems also demonstrate circadian rhythms. This is particularly the
      case for the proliferating cells within the system. In fact, all proliferating
      cell populations exhibit their own circadian rhythm, which has important
      implications for disease and the treatment of disease. Stem cell chronobiology is
      particularly important because the treatment of cancer can be significantly
      affected by the time of day a drug is administered. This protocol provides a
      basis for measuring hematopoietic stem cell circadian rhythm for future stem cell
      chronotherapeutic applications. 

PMID- 25388389
TI  - Cryopreservation of human pluripotent stem cells: a general protocol.
AB  - Cryopreservation is an essential technique to preserve stem cells,
      semipermanently sustaining their potentials. There are two main approaches of
      cryopreservation for human pluripotent stem cells (hPSCs). The first is the
      vitrification, which involves instantaneous freeze and thaw of hPSCs. The second
      is the conventional slow-cooling method and a rapid thaw. Both cryopreservation
      protocols have been standardized and optimized to yield high survivability of
      hPSCs. 

PMID- 25388390
TI  - Biological differences between native and cultured mesenchymal stem cells:
      implications for therapies.
AB  - We describe the current knowledge of the surface marker phenotype of native bone
      marrow mesenchymal stem/stromal cells (MSCs) in humans and in mouse models,
      highlighting similarities in the MSC marker "signature" between the two species.
      The chapter proceeds to discuss the published literature pertaining to native MSC
      topography and their interactions with hematopoietic stem cells and their
      progeny, as well as with blood vessels and nerve endings. Additionally, the
      chapter describes phenotypic and functional "drifts" that occur in MSC
      preparations as they are taken out of their native bone marrow microenvironment
      and induced to proliferate in vitro (in the presence of animal or human serum).
      We propose that the understanding of the biology of MSCs in their native niches
      in the bone marrow could lead to future developments in the treatment of
      hematological diseases such as multiple myeloma. Additionally, this knowledge
      would assist in the development of more "natural" MSC culture conditions, best
      preserving MSC functionality including their homing potential in order to
      optimize MSC transplantation in the context of graft-versus-host and other
      diseases. 

PMID- 25388391
TI  - The use of multiparameter flow cytometry and cell sorting to characterize native
      human bone marrow mesenchymal stem cells (MSC).
AB  - This chapter describes a method for identification, phenotypic analysis, and cell
      sorting of rare mesenchymal stem cells (MSCs) from human bone marrow (BM)
      aspirates. The native BM MSC population is identified based on the CD45(
      /low)CD271(+) phenotype. The method consists of three related procedures:
      Procedure 1 involves a microbead-based pre-enrichment step. Two other procedures
      describe direct flow cytometric analysis of MSCs following the isolation of the
      mononuclear cell (MNC) fraction (Procedure 2) or more rapidly, following a simple
      ammonium chloride-based red cell lysis (Procedure 3). Recently described multi
      lineage transcript expression in the CD45(-/low)CD271(+) cells suggests that the
      native BM MSC fraction could be further subdivided into functionally distinct
      subpopulations. The present protocols are hoped to help MSC biologists to enter
      this exciting field of research and to take it forward towards a better
      understanding of MSC biology in vivo. 

PMID- 25388392
TI  - High yield recovery of equine mesenchymal stem cells from umbilical cord
      matrix/Wharton's jelly using a semi-automated process.
AB  - Umbilical cord is an abundant source of perinatal, plastic adherent mesenchymal
      stem cells (UC-MSCs). UC-MSCs exhibit robust stemness and strong
      immunosuppressive and regenerative effects in vivo. This protocol describes
      enzymatic and mechanical dissociation of umbilical cord matrix (Wharton's jelly)
      that results in efficient isolation of large numbers of fresh nucleated umbilical
      cord regenerative cells (UC-RCs) that, when cultured on plastic, exhibit similar
      characteristics of UC-MSCs. This protocol potentially alleviates the need for
      culture expansion to obtain large numbers of cells required for clinical
      application. Dissociation is achieved with a blend of collagenase and neutral
      proteases with agitation at 37  degrees C in a semi-automatic system. Average
      expected yield is 1.65 * 10(6) cells/g tissue with 93 % viability. This protocol
      has been successfully used to isolate an uncultured nucleated regenerative cell
      population (also referred to as stromal vascular fraction or SVF) from surgically
      debrided skin and from human, equine, and canine adipose tissue. The procedure
      requires less than 30 min for tissue dissection and less than 100 min for cell
      extraction. Quickly obtaining a large number of UC-RCs that have pluripotent
      differentiation capacity without the complexity and risks of culture expansion
      could simplify and expand the use of UC-RCs in clinical as well as research
      applications. 

PMID- 25388393
TI  - Isolation and functional assessment of cutaneous stem cells.
AB  - The epidermis and associated appendages of the skin represent a multi-lineage
      tissue that is maintained by perpetual rounds of renewal. During homeostasis,
      turnover of epidermal lineages is achieved by input from regionalized
      keratinocytes stem or progenitor populations with little overlap from neighboring
      niches. Over the last decade, molecular markers selectively expressed by a number
      of these stem or progenitor pools have been identified, allowing for the
      isolation and functional assessment of stem cells and genetic lineage tracing
      analysis within intact skin. These advancements have led to many fundamental
      observations about epidermal stem cell function such as the identification of
      their progeny, their role in maintenance of skin homeostasis, or their
      contribution to wound healing. In this chapter, we provide a methodology to
      identify and isolate epidermal stem cells and to assess their functional role in
      their respective niche. Furthermore, recent evidence has shown that the
      microenvironment also plays a crucial role in stem cell function. Indeed,
      epidermal cells are under the influence of surrounding fibroblasts, adipocytes,
      and sensory neurons that provide extrinsic signals and mechanical cues to the
      niche and contribute to skin morphogenesis and homeostasis. A better
      understanding of these microenvironmental cues will help engineer in vitro
      experimental models with more relevance to in vivo skin biology. New approaches
      to address and study these environmental cues in vitro will also be addressed. 

PMID- 25388394
TI  - Isolation of adult stem cell populations from the human cornea.
AB  - Corneal blindness is a leading cause of vision loss globally. From a tissue
      engineering perspective, the cornea represents specific challenges in respect to
      isolating, stably expanding, banking, and effectively manipulating the various
      cell types required for effective corneal regeneration. The current research
      trend in this area focuses on a combined stem cell component with a biological or
      synthetic carrier or engineering scaffold. Corneal derived stem cells play an
      important role in such strategies as they represent an available supply of cells
      with specific abilities to further generate corneal cells in the long term. This
      chapter describes the isolation protocols of the epithelial stromal and
      endothelial stem cell populations. 

PMID- 25388395
TI  - Advanced imaging and tissue engineering of the human limbal epithelial stem cell
      niche.
AB  - The limbal epithelial stem cell niche provides a unique, physically protective
      environment in which limbal epithelial stem cells reside in close proximity with
      accessory cell types and their secreted factors. The use of advanced imaging
      techniques is described to visualize the niche in three dimensions in native
      human corneal tissue. In addition, a protocol is provided for the isolation and
      culture of three different cell types, including human limbal epithelial stem
      cells from the limbal niche of human donor tissue. Finally, the process of
      incorporating these cells within plastic compressed collagen constructs to form a
      tissue-engineered corneal limbus is described and how immunohistochemical
      techniques may be applied to characterize cell phenotype therein. 

PMID- 25388396
TI  - Isolation and characterization of stem cells in the adult mammalian ovary.
AB  - Female mammals are born with a fixed pool of germ cells, which does not replenish
      during adult life. However, this has been recently challenged and adult ovaries
      produce oocytes throughout adult life just like sperm in the testes. Evidence is
      accumulating on the presence of ovarian stem cells, but the need for robust
      protocols to isolate, identify, further characterize, and subject them to various
      functionality tests is essential. Knowledge about the function and potential of
      ovarian stem cells is well demonstrated by various groups, but their true
      identity remains elusive because of the variability in the approaches used to
      identify them by different groups. In order to address this we have made attempts
      to compile our protocols to isolate, identify, characterize, and culture the stem
      cells using different animal models including human. Two distinct populations of
      stem cells exist in adult mammalian ovary, including very small embryonic-like
      stem cells (VSELs) and the progenitors termed ovarian germ stem cells (OGSCs).
      VSELs are relatively quiescent and undergo asymmetric cell division to give rise
      to OGSCs, which divide rapidly, occasionally form germ cell nests and undergo
      meiosis and differentiation into oocytes, which are surrounded by granulosa cells
      to assemble as primordial follicles. 

PMID- 25388397
TI  - Clonal culture of adult mouse lung epithelial stem/progenitor cells.
AB  - Clonal culture of stem cells is crucial for their identification, and the
      characterization of the cellular and molecular mechanisms that regulate their
      proliferation and differentiation. In the adult mouse lung, epithelial
      stem/progenitor cells are defined by the phenotype CD45(neg) CD31(neg) EpCAM(pos)
      CD104(pos) CD24(low). Here we describe a tissue dissociation and flow cytometry
      strategy for the detection and isolation of adult mouse lung epithelial
      stem/progenitor cells, and a three-dimensional colony-forming assay for their
      clonal culture in vitro. 

PMID- 25388398
TI  - Culture and characterization of mammary cancer stem cells in mammospheres.
AB  - Mammospheres (MMs) are a model for culturing and maintaining mammary gland stem
      cells (SCs) or cancer stem cells (CSCs) ex situ. As MMs recapitulate the micro
      niche of the mammary gland or a tumor, MMs are a model for studying the
      properties of SCs or CSCs, and for mapping, isolating, and characterizing the
      SC/CSC generated lineages. Cancer stem cells share with normal SCs the properties
      of self-renewal and the capacity to generate all cell types and organ structures
      of the mammary gland. Analysis of human tumor samples suggests that CSCs are
      heterogeneous in terms of proliferation and differentiation potential.
      Mammospheres from CSCs likewise display heterogeneity. This heterogeneity makes
      analysis of CSC generated MMs challenging. To identify the unique and diverse
      properties of MM derived CSCs, comparative analysis with MMs obtained from normal
      SCs is required. Here we present protocols for identifying and enriching cells
      with SC features from a cancer cell line using the LA7CSCs as a model. A
      comprehensive and comparative approach for identifying, isolating, and
      characterizing MMs from SCs and CSCs from human breast is also introduced. In
      addition, we describe detailed procedures for identifying, isolating, and
      characterizing mammary gland specific cell types, generated during MM formation. 

PMID- 25388399
TI  - Isolation and culture of primary glioblastoma cells from human tumor specimens.
AB  - Cultured tumor cells are a central tool in cancer research and have provided
      fundamental insights in tumor biology. Recent evidence, however, indicates that
      classically established cell lines from different tumors, including glioblastoma,
      do not fully reflect the genotypes and phenotypes of the respective primary
      tumors. By contrast, primary cells, isolated from human tumor samples and
      maintained in serum-free spheroid cultures at low passage under defined growth
      factor conditions, reproduce key aspects of tumor cell physiology much more
      faithfully. Among the tumor cell characteristics that are better represented in
      primary glioblastoma cell cultures is the self-renewal and differentiation
      potential of the tumor cells. Indeed, a large body of evidence from the past
      decade indicates that glioblastomas and other tumors are composed of a hierarchy
      of heterogeneous types of cells, which are generated and maintained by cells that
      share characteristics of stem cells. This cancer stem cell/tumor initiating cell
      population is optimally preserved and maintained in primary glioblastoma
      cultures. Here, we describe a method for the isolation and culture of primary
      tumor cells from human glioblastomas in serum-free conditions, which allows the
      routine generation and proper maintenance of tumor cells as spheroid cultures.
      Such primary tumor cultures can serve as a model of choice for the study of the
      mechanisms behind key aspects of glioblastoma biology, including tumorigenicity,
      stem cell hierarchy, invasion, and therapeutic resistance. 

PMID- 25388400
TI  - Norwegian trauma care: a national cross-sectional survey of all hospitals
      involved in the management of major trauma patients.
AB  - BACKGROUND: Approximately 10% of the Norwegian population is injured every year,
      with injuries ranging from minor injuries treated by general practitioners to
      major and complex injuries requiring specialist in-hospital care. There is a lack
      of knowledge concerning the caseload of potentially severely injured patients in
      Norwegian hospitals. Aim of the study was to describe the current status of the
      Norwegian trauma system by identifying the number and the distribution of
      contributing hospitals and the caseload of potentially severely injured trauma
      patients within these hospitals. METHODS: A cross-sectional survey with a
      structured questionnaire was sent in the summer of 2012 to all Norwegian
      hospitals that receive trauma patients. These were defined by number of trauma
      team activations in the included hospitals. A literature review was performed to
      assess over time the development of hospitals receiving trauma patients. RESULTS:
      Forty-one hospitals responded and were included in the study. In 2011, four
      trauma centres and 37 acute care hospitals received a total of 6,570 trauma
      patients. Trauma centres received 2,175 (33%) patients and other hospitals
      received 4,395 (67%) patients. There were significant regional differences
      between health care regions in the distribution of trauma patients between trauma
      centres and acute care hospitals. More than half (52.5%) of the hospitals
      received fewer than 100 patients annually. The national rate of hospital
      admission via trauma teams was 13 per 10,000 inhabitants. There was a 37% (from
      65 to 41) reduction in the number of hospitals receiving trauma patients between
      1988 and 2011. CONCLUSIONS: In 2011, hospital acute trauma care in Norway was
      delivered by four trauma centres and 37 acute care hospitals. Many hospitals
      still receive a small number of potentially severely injured patients and only a
      few hospitals have an electronic trauma registry. Future development of the
      Norwegian trauma system needs to address the challenge posed by a scattered
      population and long geographical distances. The implementation of a trauma
      system, carefully balanced between centres with adequate caseloads against time
      from injury to hospital care, is needed and has been shown to have a beneficial
      effect in countries with comparable challenges.

PMID- 25388401
TI  - Hydrogen sulfide functions as a neuromodulator to regulate striatal
      neurotransmission in a mouse model of Parkinson's disease.
AB  - Hydrogen sulfide (H2S), a novel endogenous gasotransmitter, has been considered a
      neuromodulator to enhance hippocampal long-term potentiation and exerts
      neuroprotective effects against neurotoxin-induced neurodegeneration in rodent
      models of Parkinson's disease (PD). However, whether H2S can function as a
      neuromodulator to regulate the levels of nigrostriatal neurotransmitters and then
      impact the vulnerability of dopaminergic (DA) neurons in response to neurotoxins
      remains unknown. For this study, we prepared a 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine plus probenecid (MPTP/p)-induced mouse subacute model of PD to
      explore the modulatory effect of H2S on monoamine and amino acid
      neurotransmitters in the striatum of MPTP-treated mice. This study shows that
      NaHS (an H2S donor, 5.6 mg/kg/day, i.p.) administration improves the survival
      rate and significantly ameliorates the weight loss of MPTP-treated mice. NaHS
      treatment attenuated MPTP-induced neuronal damage, restored the diminution of DA
      neurons, and suppressed the overactivation of astrocytes in the mouse striatum.
      Additionally, NaHS upregulated striatal serotonin levels and modulated the
      balance of excitatory glutamate and the inhibitory gamma-aminobutyric acid system
      in response to MPTP challenge. The current study indicates that H2S may function
      as an effective neuromodulator to regulate striatal neurotransmission and
      provides insight into the potential of H2S for PD therapy.

PMID- 25388402
TI  - Axonal neuropathy in female carriers of the fragile X premutation with fragile x
      associated tremor ataxia syndrome.
AB  - INTRODUCTION: In this study we examined whether females with the fragile X
      associated tremor ataxia syndrome (FXTAS) and non-FXTAS premutation carriers have
      electrophysiological signs of underlying peripheral neuropathy. METHODS: Nerve
      conduction studies (NCS) were performed on 19 women with FXTAS, 20 non-FXTAS
      carriers, and 26 age-matched controls. The results were compared with existing
      data on corresponding male carriers. RESULTS: Women with FXTAS and non-FXTAS
      carriers had reduced sensory nerve action potential amplitudes. Also, there was a
      strong trend for reduced compound muscle action potential amplitudes in women
      with FXTAS, but not in non-FXTAS carriers. No significant slowing of nerve
      conduction velocities, prolongation of F-wave latencies, or associations with
      molecular measures was observed. CONCLUSIONS: This study suggests an underlying
      axonal neuropathy in women with FXTAS. However, in comparison to men with FXTAS,
      the NCS abnormalities in women were less severe, possibly due to the effect of a
      normal X chromosome.

PMID- 25388403
TI  - The impact of adiposity on adipose tissue-resident lymphocyte activation in
      humans.
AB  - BACKGROUND/OBJECTIVES: The presence of T lymphocytes in human adipose tissue has
      only recently been demonstrated and relatively little is known of their potential
      relevance in the development of obesity-related diseases. We aimed to further
      characterise these cells and in particular to investigate how they interact with
      modestly increased levels of adiposity typical of common overweight and obesity.
      SUBJECTS/METHODS: Subcutaneous adipose tissue and fasting blood samples were
      obtained from healthy males aged 35-55 years with waist circumferences in lean
      (<94 cm), overweight (94-102 cm) and obese (>102 cm) categories. Adipose tissue
      resident CD4+ and CD8+ T lymphocytes together with macrophages were identified by
      gene expression and flow cytometry. T lymphocytes were further characterised by
      their expression of activation markers CD25 and CD69. Adipose tissue inflammation
      was investigated using gene expression analysis and tissue culture. RESULTS:
      Participants reflected a range of adiposity from lean to class I obesity.
      Expression of CD4 (T-helper cells) and CD68 (macrophage), as well as FOXP3 RNA
      transcripts, was elevated in subcutaneous adipose tissue with increased levels of
      adiposity (P<0.001, P<0.001 and P=0.018, respectively). Flow cytometry revealed
      significant correlations between waist circumference and levels of CD25 and CD69
      expression per cell on activated adipose tissue-resident CD4+ and CD8+ T
      lymphocytes (P-values ranging from 0.053 to <0.001). No such relationships were
      found with blood T lymphocytes. This increased T lymphocyte activation was
      related to increased expression and secretion of various pro- and anti
      inflammatory cytokines from subcutaneous whole adipose tissue explants.
      CONCLUSIONS: This is the first study to demonstrate that even modest levels of
      overweight/obesity elicit modifications in adipose tissue immune function. Our
      results underscore the importance of T lymphocytes during adipose tissue
      expansion, and the presence of potential compensatory mechanisms that may work to
      counteract adipose tissue inflammation, possibly through an increased number of T
      regulatory cells.

PMID- 25388404
TI  - Obesity is associated with more activated neutrophils in African American male
      youth.
AB  - BACKGROUND: There is emerging evidence suggesting the role of peripheral blood
      leukocytes in the pathogenesis of obesity and related diseases. However, few
      studies have taken a genome-wide approach to investigating gene expression
      profiles in peripheral leukocytes between obese and lean individuals with the
      consideration of obesity-related shifts in leukocyte types. METHOD: We conducted
      this study in 95 African Americans (AAs) of both genders (age 14-20 years, 46
      lean and 49 obese). Complete blood count with differential test (CBC) was
      performed in whole blood. Genome-wide gene expression analysis was obtained using
      the Illumina HumanHT-12 V4 Beadchip with RNA extracted from peripheral
      leukocytes. Out of the 95 participants, 64 had neutrophils stored. The validation
      study was based on real-time PCR with RNA extracted from purified neutrophils.
      RESULTS: CBC test suggested that, in males, obesity was associated with increased
      neutrophil percentage (P=0.03). Genome-wide gene expression analysis showed that,
      in males, the majority of the most differentially expressed genes were related to
      neutrophil activation. Validation of the gene expression levels of ELANE
      (neutrophil elastase) and MPO (myeloperoxidase) in purified neutrophils
      demonstrated that the expression of these two genes--important biomarkers of
      neutrophils activation--were significantly elevated in obese males (P=0.01 and
      P=0.02, respectively). CONCLUSION: The identification of increased neutrophil
      percentage and activation in obese AA males suggests that neutrophils have an
      essential role in the pathogenesis of obesity-related disease. Further functional
      and mechanistic studies on neutrophils may contribute to the development of novel
      intervention strategies reducing the burden associated with obesity-related
      health problems.

PMID- 25388406
TI  - The not so clean plate club: food self-served won't always result in food eaten.

PMID- 25388405
TI  - Maternal caffeine intake during pregnancy and risk of obesity in offspring: a
      prospective cohort study.
AB  - BACKGROUND/OBJECTIVES: In-utero exposures through adverse fetal programming are
      emerging as an important contributing factor to the epidemic of childhood
      obesity. This study examines the impact of in-utero exposure to caffeine on the
      risk of childhood obesity in offspring. SUBJECTS/METHODS: A prospective study of
      pregnant women with 15 years follow-up of their offspring was conducted to
      examine the impact of in-utero exposure to caffeine on the risk of childhood
      obesity. Maternal caffeine intake was prospectively ascertained during pregnancy
      and outcome measures (body mass index (BMI)) were ascertained from medical
      charts, with 17 BMI measurements per child, on average, during the follow-up
      period. Potential confounders including known perinatal risk factors for
      childhood obesity were adjusted for using the generalized estimating equations
      model with repeated measurements. RESULTS: After controlling for potential
      confounders, compared with those without caffeine exposure, in-utero exposure to
      caffeine overall is associated with 87% increased risk of childhood obesity: odds
      ratio (OR) =1.87, 95% confidence interval (CI): 1.12-3.12. This association
      demonstrated a dose-response relationship: OR=1.77 (1.05-3.00) for maternal daily
      caffeine intake <150 mg per day, OR=2.37 (1.24-4.52) for caffeine intake ?150 mg
      per day during pregnancy, respectively. We also observed a linear relationship:
      every one unit increase (log10 scale) in the amount of maternal caffeine intake
      was associated with 23% increased risk of obesity in offspring. The dose-response
      relationship appears stronger for persistent obesity than for transitory obesity
      (occasional high BMI), and for girls than for boys. CONCLUSIONS: We observed an
      association of in-utero exposure to caffeine with increased risk of childhood
      obesity. If this observation is further replicated in other studies, the finding
      will contribute to the understanding of fetal programming of childhood diseases
      and development of intervention strategy to prevent childhood obesity.

PMID- 25388407
TI  - Transaldolase deficiency caused by the homozygous p.R192C mutation of the TALDO1
      gene in four Emirati patients with considerable phenotypic variability.
AB  - Transaldolase deficiency is a heterogeneous disorder of carbohydrate metabolism
      characterized clinically by dysmorphic features, cutis laxa, hepatosplenomegaly,
      hepatic fibrosis, pancytopenia, renal and cardiac abnormalities, and urinary
      excretion of polyols. This report describes four Emirati patients with
      transaldolase deficiency caused by the homozygous p.R192C missense mutation in
      TALDO1 displaying wide phenotypic variability. The patients had variable clinical
      presentations including hepatosplenomegaly, pancytopenia, liver failure,
      proteinuria, hydrops fetalis, cardiomyopathy, and skin manifestations (e.g.,
      dryness, cutis laxa, ichthyosis, telangiectasias, and hemangiomas). Biochemical
      analyses including urinary concentration of polyols were consistent with
      transaldolase deficiency. The mutation p.R192C was previously identified in an
      Arab patient, suggesting a founder effect in Arab populations. CONCLUSION: The
      above findings support the premise that biallelic mutations in TALDO1 are
      responsible for transaldolase deficiency and confirm the broad phenotypic
      variability of this condition, even with the same genotype.

PMID- 25388408
TI  - Gentamicin trough levels using a simplified extended-interval dosing regimen in
      preterm and term newborns.
AB  - To evaluate a simplified gentamicin extended-interval dosing regimen in a large
      cohort of preterm and term newborns, we conducted a retrospective cohort study
      over a 4-year period. All inborn newborns who received gentamicin for the first
      episode of suspected or proven sepsis were eligible. Newborns received 4 mg/kg
      gentamicin intravenously 24-hourly, except for those at <28 weeks of gestation
      who received gentamicin 36-hourly. Trough levels were taken before the third dose
      and considered non-toxic if <=2 MUg/mL. Infants were analysed in gestational age
      subgroups: <28 weeks, 28-31 weeks, 32-35 weeks, 36-39 weeks and >=40 weeks.
      Newborns who received indomethacin co-medication were analysed separately. Nine
      hundred ninety-three newborns, gestational age range 23(+2)-42(+1) weeks, birth
      weight range 397-5936 g, were included. The median (interquartile range (IQR))
      gentamicin trough level for all newborns was 1.3 MUg/mL (0.8-1.7). Ninety per
      cent of newborns had non-toxic trough levels. The incidence of trough levels >2
      MUg/mL was between 2.2 and 9.7 % in all subgroups except for infants born at 28
      31 weeks of gestation, where 21.7 % of trough levels were >2 MUg/mL. Indomethacin
      co-medication significantly increased the median gentamicin trough level in
      preterm infants at <32 weeks of gestation. CONCLUSION: This study demonstrates
      that simplified gentamicin dosage regimens are feasible. Prospective evaluations
      are required to establish safety profiles.

PMID- 25388409
TI  - Syngnathia and obstructive apnea in a case of popliteal pterygium syndrome.
AB  - We describe an infant with popliteal pterygia, syngnathia, cleft lip and palate,
      and retrognathia diagnosed with popliteal pterygium syndrome (PPS). The neonatal
      course was complicated by severe obstructive apnea necessitating tracheostomy.
      CONCLUSION: This report illustrates the potential for airway compromise in PPS
      patients and the need for thorough neonatal airway assessment.

PMID- 25388410
TI  - Development of a short-form Health Literacy Dental Scale (HeLD-14).
AB  - OBJECTIVE: To develop a short-form version of the 29-item Health Literacy in
      Dentistry (HeLD-29) instrument. METHODS: Deriving the short-form version used
      data from a cross-sectional study of 400 indigenous Australians aged 18+ years in
      Port Augusta, South Australia, which was split to enable short-form testing (N =
      191). Internal reliability analysis, factor analysis and regression analysis were
      undertaken to derive a subset (HeLD-14) questionnaire. Its validity was evaluated
      by assessing associations with socio-demographic and self-reported oral health
      variables. Internal consistency of the HeLD-14 was evaluated using Cronbach's
      coefficient alpha. A HeLD-14 scale was derived from regression analysis. RESULTS:
      The HeLD-14 accounted for 94% of variance in the HeLD-29 mean scores; had high
      reliability (alpha = 0.88); contained questions from each of the seven conceptual
      dimensions of the HeLD-29; and had a good distribution of prevalence for
      individual questions. HeLD-14 scores and HeLD-29 scores displayed the same
      pattern of variation among socio-demographic groups of indigenous Australians.
      Cronbach's alpha for the HeLD-14 was 0.87. In a multivariable analysis, the same
      socio-demographic and self-reported oral health variables were associated (P <
      0.05) with both the HeLD-29 and the HeLD-14. CONCLUSIONS: The reliability,
      validity and precision of the short-form version (HeLD-14) were acceptable when
      tested in a sample of rural dwelling indigenous Australians. However, it will be
      important to replicate these findings in other populations before it can be used
      in health services research to determine the effects of interventions or programs
      aimed at improving oral health outcomes. This short form will be easy and
      efficient for use in research and clinical settings.

PMID- 25388411
TI  - Transparent thin films of Cu-TiO2 with visible light photocatalytic activity.
AB  - Thin films of Cu-TiO2 with a high level of transparency were prepared by a dip
      coating procedure on the glass surface. CuCl2 was used as a copper precursor
      added during sol-gel synthesis of TiO2. The extension of optical absorption into
      the visible region of as-prepared thin films was indicated by UV/Vis
      spectroscopy. Only the anatase phase was detected by X-ray diffraction analysis
      (XRD). The presence of copper in the structure of thin films was confirmed by
      energy dispersive X-ray spectrometry (EDS). The significant rate of phenol and 4
      chlorophenol mineralization was observed during visible light irradiation. The
      photocatalytic activity of the prepared thin films is correlated with the optimum
      copper content in the structure. Copper in metallic form and cupric oxides were
      not detected by XRD and scanning electron microscopy analysis. It is suggested
      that copper may exist as dispersed ions in the TiO2 lattice. 

PMID- 25388412
TI  - UV-excitation from an experimental perspective: frequency resolved.
AB  - Electronic spectroscopy of DNA bases in the gas phase provides detailed
      information about the electronic excitation, which places the molecule in the
      Franck-Condon region in the excited state and thus prepares the starting
      conditions for excited-state dynamics. Double resonance or hole-burning
      spectroscopy in the gas phase can provide such information with isomer
      specificity, probing the starting potential energy landscape as a function of
      tautomeric form, isomeric structure, or hydrogen bonded or stacked cluster
      structure. Action spectroscopy, such REMPI, can be affected by excited-state
      lifetimes. 

PMID- 25388413
TI  - Increased reaction time variability in attention-deficit hyperactivity disorder
      as a response-related phenomenon: evidence from single-trial event-related
      potentials.
AB  - BACKGROUND: Increased intra-subject variability (ISV) in reaction times (RTs) is
      a promising endophenotype for attention-deficit hyperactivity disorder (ADHD) and
      among the most robust hallmarks of the disorder. ISV has been assumed to
      represent an attentional deficit, either reflecting lapses in attention or
      increased neural noise. Here, we use an innovative single-trial event-related
      potential approach to assess whether the increased ISV associated with ADHD is
      indeed attributable to attention, or whether it is related to response-related
      processing. METHODS: We measured electroencephalographic responses to working
      memory oddball tasks in patients with ADHD (N = 20, aged 11.3 +/- 1.1) and
      healthy controls (N = 25, aged 11.7 +/- 1.1), and analysed these data with a
      recently developed method of single-trial event-related potential analysis.
      Estimates of component latency variability were computed for the stimulus-locked
      and response-locked forms of the P3b and the lateralised readiness potential
      (LRP). RESULTS: ADHD patients showed significantly increased ISV in behavioural
      ISV. This increased ISV was paralleled by an increase in variability in response
      locked event-related potential latencies, while variability in stimulus-locked
      latencies was equivalent between groups. This result held across the P3b and LRP.
      Latency of all components predicted RTs on a single-trial basis, confirming that
      all were relevant for speed of processing. CONCLUSIONS: These data suggest that
      the increased ISV found in ADHD could be associated with response-end, rather
      than stimulus-end processes, in contrast to prevailing conceptions about the
      endophenotype. This mental chronometric approach may also be useful for exploring
      whether the existing lack of specificity of ISV to particular psychiatric
      conditions can be improved upon.

PMID- 25388414
TI  - Increased risk for intracranial arterial stenosis in subjects with coronary
      artery calcification.
AB  - BACKGROUND AND PURPOSE: Intracranial arterial stenosis (ICAS) is considered an
      important cause of stroke in Asians. Coronary artery calcification (CAC) is a
      surrogate marker for subclinical atherosclerosis. We aimed to analyze the
      association of ICAS assessed by transcranial Doppler ultrasonography and CAC in
      middle-aged Korean population. METHODS: This study included 10 550 participants
      (81.3% men, mean age 43 years) from a health screening program, in whom
      transcranial Doppler ultrasonography was used to detect >50% intracranial
      stenosis based on criteria modified from the stroke outcomes and neuroimaging of
      intracranial atherosclerosis trial. Multidetector computed tomography was used to
      assess coronary artery calcium score (CACS). CAC grade (0, 1-100, and >100) was
      defined by CACS. RESULTS: The subjects with CAC showed significantly higher
      proportion of subjects with ICAS compared with those without CAC (4.4% versus
      2.8%; P<0.01). Conversely, the subjects with ICAS showed significantly higher
      proportion of subjects with CAC (24.8% versus 17.1%; P<0.01). When logistic
      regression analysis was performed with ICAS as the dependent variable, the
      presence of CAC showed significantly increased risk for ICAS after adjustment for
      confounding variables (odds ratio, 1.439; 95% confidence interval, 1.095-1.891).
      When CACS grade was included in the model, the odds ratio for ICAS was the
      highest in subjects with CACS >400 compared with those with CACS=0 (odds ratio,
      2.754; 95% confidence interval, 1.205-2.936). CONCLUSIONS: The risk for ICAS was
      significantly increased in middle-aged Korean subjects with CAC compared with
      that in those without CAC. These findings suggest the possibility of a separate
      undetected atherosclerotic focus in subjects with 1 atherosclerotic event.

PMID- 25388415
TI  - Sensitivity of diffusion- and perfusion-weighted imaging for diagnosing acute
      ischemic stroke is 97.5%.
AB  - BACKGROUND AND PURPOSE: MRI using diffusion-weighted imaging (DWI) is the most
      sensitive diagnostic imaging modality for early detection of ischemia, but how
      accurate is it and how much does perfusion-weighted imaging (PWI) add to the
      sensitivity have to be known. METHODS: In this single-center study, we collected
      epidemiological, imaging, and outcome data on all patients with stroke undergoing
      MRI-based treatment with intravenous tissue-type plasminogen activator at our
      center from 2004 to 2010. The DWI negative patients were identified, and we
      calculated the sensitivity and specificity of DWI and additional PWI for
      diagnosing acute ischemic stroke. We compared DWI positive and negative patients
      to identify characteristics associated with DWI negativity. RESULTS: Five hundred
      sixty-nine consecutive patients were treated with intravenous tissue-type
      plasminogen activator on the basis of an acute MRI. A DWI lesion was evident in
      518 patients. Forty-seven patients were DWI negative; however, a relevant PWI
      lesion was found in 33 of these patients. Four stroke mimics were treated with
      intravenous tissue-type plasminogen activator and 1 of these patients had a DWI
      lesion. Thus, 8% of all patients with stroke were DWI negative. The combination
      of DWI and PWI resulted in a sensitivity of 97.5% for the ischemic stroke
      diagnosis. DWI negativity was associated with less severe strokes, location in
      the posterior circulation, a longer time from onset to scan, and an improved 90
      day outcome. The cause of small-vessel disease was more likely to be DWI
      negative. CONCLUSIONS: The combination of DWI and PWI before intravenous tissue
      type plasminogen activator confirms the diagnosis in 97.5% of all ischemic
      strokes.

PMID- 25388416
TI  - Early transfer of patients with stroke to comprehensive stroke centers is not
      necessary.

PMID- 25388417
TI  - Deficiency of the stroke relevant HDAC9 gene attenuates atherosclerosis in accord
      with allele-specific effects at 7p21.1.
AB  - BACKGROUND AND PURPOSE: Recent genome-wide association studies identified the
      histone deacetylase 9 (HDAC9) gene region as a major risk locus for large-vessel
      stroke and coronary artery disease. However, the mechanisms linking variants at
      this locus to vascular risk are poorly understood. In this study, we investigated
      the candidacy and directionality of HDAC9 in atherosclerosis and analyzed
      associations between risk alleles at 7p21.1 and plaque characteristics. METHODS:
      Allele-dependent expression of HDAC9 was analyzed in human peripheral blood
      mononuclear cells of healthy donors. Effects of HDAC9 deficiency on
      atherosclerotic plaques were investigated in 18- and 28-week-old ApoE(-/-) mice
      by histology and immunohistochemistry. We further performed detailed plaque
      phenotyping and genotyping of rs2107595, the lead single-nucleotide polymorphism
      for large-vessel stroke, in carotid endarterectomy samples of 1858 subjects from
      the Athero-Express study. RESULTS: Gene expression studies in peripheral blood
      mononuclear cells revealed increased mRNA levels of HDAC9 but not of neighboring
      genes (TWIST1/FERD3L) in risk allele carriers of rs2107595. Compared with
      HDAC9(+/+)ApoE(-/-) mice, HDAC9(-/-)ApoE(-/-) mice exhibited markedly reduced
      lesion sizes throughout atherosclerotic aortas and significantly less advanced
      lesions. The proportion of Mac3-positive macrophages was higher in plaques from
      HDAC9(-/-)ApoE(-/-) mice, but this was largely because of a lower proportion of
      advanced lesions. Analysis of human atherosclerotic plaques revealed no
      association between rs2107595 and specific plaque characteristics. CONCLUSIONS:
      Our results suggest that HDAC9 represents the disease-relevant gene at the stroke
      and coronary artery disease risk locus on 7p21.1, and that risk alleles in this
      region mediate their effects through increased HDAC9 expression. Targeted
      inhibition of HDAC9 might be a viable strategy to prevent atherosclerosis.

PMID- 25388418
TI  - Hospital and demographic characteristics associated with advanced primary stroke
      center designation.
AB  - BACKGROUND AND PURPOSE: Despite evidence that primary stroke center (PSC)
      certification is associated with improvements in care and outcome, only a
      minority of hospitals have achieved this certification. We sought to determine
      hospital-based factors associated with achievement of PSC certification. METHODS:
      We used the 2011 American Hospital Association survey and the 2010 national
      census for population and household data to identify potential hospital and
      demographic factors influencing certification as a PSC by the Joint Commission,
      Healthcare Facilities Accreditation Program, and DNV Healthcare. RESULTS: Of the
      3696 hospitals to complete the survey, 3069 fulfilling study criteria included
      908 PSC (31%) and 2161 non-PSC. Independent hospital characteristics associated
      with PSC certification were Joint Commission accreditation (odds ratio [OR], 3.5;
      95% confidence interval [CI], 2.4-5.0), increasing size (per quartile in number
      of beds; OR, 2.5; 95% CI, 2.1-3.1) and inpatient neurological services (OR, 3.2;
      95% CI, 2.4-4.6), number of households per zip code (per 1000 households; OR,
      1.1; 95% CI, 1.0-1.2), increasing Hispanic population (by 10% increase; OR, 1.1;
      95% CI, 1.0-1.2), and income per household (per $10 000; OR, 1.2; 95% CI, 1.1
      1.3). Designation as a sole community provider (OR, 0.22; 0.10-0.47) or
      governmental hospital control (0.61; 0.44-0.84) was associated with
      noncertification. CONCLUSIONS: Less than 1 in 3 hospitals has achieved
      certification as an PSC. Potential areas of improvement include increasing
      certification of governmental-controlled hospitals.

PMID- 25388420
TI  - Early transfer of stroke patients to comprehensive stroke centers: David and
      Goliath.

PMID- 25388421
TI  - Early transfer of patients with stroke to comprehensive centers is necessary.

PMID- 25388419
TI  - Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the
      vascular effects of infection in pediatric stroke study.
AB  - BACKGROUND AND PURPOSE: Although arteriopathies are the most common cause of
      childhood arterial ischemic stroke, and the strongest predictor of recurrent
      stroke, they are difficult to diagnose. We studied the role of clinical data and
      follow-up imaging in diagnosing cerebral and cervical arteriopathy in children
      with arterial ischemic stroke. METHODS: Vascular effects of infection in
      pediatric stroke, an international prospective study, enrolled 355 cases of
      arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A
      neuroradiologist and stroke neurologist independently reviewed vascular imaging
      of the brain (mandatory for inclusion) and neck to establish a diagnosis of
      arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging
      alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee,
      including a second neuroradiologist and stroke neurologist, adjudicated
      disagreements. Using the final diagnosis as the gold standard, we calculated the
      sensitivity and specificity of each step. RESULTS: Cases were aged median 7.6
      years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was
      previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required
      adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%),
      possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1,
      90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and
      100%), as was agreement between reviewers (kappa=0.77, 0.81, and 0.78).
      CONCLUSIONS: Clinical data and follow-up imaging help, yet uncertainty in the
      diagnosis of childhood arteriopathy remains. This presents a challenge to better
      understanding the mechanisms underlying these arteriopathies and designing
      strategies for prevention of childhood arterial ischemic stroke.

PMID- 25388422
TI  - Do primary stroke centers occur randomly?

PMID- 25388423
TI  - Myoblast-mediated gene therapy improves functional collateralization in chronic
      cerebral hypoperfusion.
AB  - BACKGROUND AND PURPOSE: Direct extracranial-intracranial bypass surgery for
      treatment of cerebral hemodynamic compromise remains hindered by complications
      but alternative simple and safe indirect revascularization procedures, such as an
      encephalomyosynangiosis (EMS), lack hemodynamic efficiency. Here, the myoblast
      mediated transfer of angiogenic genes presents an approach for induction of
      therapeutic collateralization. In this study, we tested the effect of myoblast
      mediated delivery of vascular endothelial growth factor-A (VEGF) to the
      muscle/brain interface of an EMS in a model of chronic cerebral hypoperfusion.
      METHODS: Permanent unilateral internal carotid artery-occlusion was performed in
      adult C57/BL6 mice with or without (no EMS) surgical grafting of an EMS followed
      by implantation of monoclonal mouse myoblasts expressing either VEGF164 or an
      empty vector (EV). Cerebral hemodynamic impairment, transpial collateralization,
      angiogenesis, mural cell investment, microvascular permeability, and cortical
      infarction after ipsilateral stroke were assessed by real-time laser speckle
      blood flow imaging, 2- and 3-dimensional immunofluorescence and MRI. RESULTS:
      VEGF-expressing myoblasts improved hemodynamic rescue by day 14 (no EMS 37+/-21%,
      EV 42+/-9%, VEGF 48+/-12%; P<0.05 for VEGF versus no EMS and versus EV), together
      with the EMS take rate (VEGF 60%, EV 18.2%; P<0.05) and angiogenesis of mature
      cortical microvessels below the EMS (P<0.05 for VEGF versus EV). Importantly,
      functional and morphological results were paralleled by a 25% reduction of
      cortical infarction after experimental stroke on the side of the EMS.
      CONCLUSIONS: Myoblast-mediated VEGF supplementation at the target site of an EMS
      could help overcome the clinical dilemma of poor surgical revascularization
      results and provide protection from ischemic stroke.

PMID- 25388425
TI  - Stroke literature synopses: basic science.

PMID- 25388424
TI  - Grading and interpretation of white matter hyperintensities using statistical
      maps.
AB  - BACKGROUND AND PURPOSE: We aimed to generate rigorous graphical and statistical
      reference data based on volumetric measurements for assessing the relative
      severity of white matter hyperintensities (WMHs) in patients with stroke.
      METHODS: We prospectively mapped WMHs from 2699 patients with first-ever ischemic
      stroke (mean age=66.8+/-13.0 years) enrolled consecutively from 11 nationwide
      stroke centers, from patient (fluid-attenuated-inversion-recovery) MRIs onto a
      standard brain template set. Using multivariable analyses, we assessed the impact
      of major (age/hypertension) and minor risk factors on WMH variability. RESULTS:
      We have produced a large reference data library showing the location and quantity
      of WMHs as topographical frequency-volume maps. This easy-to-use graphical
      reference data set allows the quantitative estimation of the severity of WMH as a
      percentile rank score. For all patients (median age=69 years), multivariable
      analysis showed that age, hypertension, atrial fibrillation, and left ventricular
      hypertrophy were independently associated with increasing WMH (0-9.4%,
      median=0.6%, of the measured brain volume). For younger (<=69) hypertensives
      (n=819), age and left ventricular hypertrophy were positively associated with
      WMH. For older (>=70) hypertensives (n=944), age and cholesterol had positive
      relationships with WMH, whereas diabetes mellitus, hyperlipidemia, and atrial
      fibrillation had negative relationships with WMH. For younger nonhypertensives
      (n=578), age and diabetes mellitus were positively related to WMH. For older
      nonhypertensives (n=328), only age was positively associated with WMH.
      CONCLUSIONS: We have generated a novel graphical WMH grading (Kim statistical WMH
      scoring) system, correlated to risk factors and adjusted for age/hypertension.
      Further studies are required to confirm whether the combined data set allows
      grading of WMH burden in individual patients and a tailored patient-specific
      interpretation in ischemic stroke-related clinical practice.

PMID- 25388426
TI  - Mechanisms of fibrosis in acute liver failure.
AB  - BACKGROUND & AIMS: Acute liver failure (ALF) is a condition with high mortality
      and morbidity. Fibrosis in chronic liver disease was extensively researched,
      whereas fibrosis and underlying mechanism in acute liver failure remains unclear.
      METHODS: Hepatitis B virus related ALF patients were recruited to investigate if
      there was ongoing fibrosis by liver histology and liver stiffness
      measurement(LSM) analysis as well as fibrosis markers assay. Sera HMGB1 were
      kinetically detected in progression and remission stage of ALF. Hepatic stellate
      cell(HSC) activation by HMGB1 was explored by testing mRNA and protein level of
      alpha-SMA and collagen 1a1 by using qPCR and western blot. Autophagy induction by
      HMGB1 was explored by LC3-II conversion, autophagy flux and fluorescence.
      RESULTS: Firstly, ongoing fibrosis in progression stage of ALF was confirmed by
      histological analysis, LS measurement as well as fibrosis markers detection. HSC
      activation and autophagy induction in explanted liver tissue also revealed. Next,
      kinetic monitoring sera HMGB1 revealed elevated HMGB1 in progression stage of ALF
      vs HBsAg carrier, and drop back to base level in remission stage. Thirdly, rHMGB1
      dose dependently activated HSCs, as indicated by increased mRNA and proteins
      level in alpha-SMA and collagen 1a1. Moreover, autophagy was induced in HSC
      treated with rHMGB1, as illustrated by increased LC3 lipidation, elevated
      autophagy flux and GFP-LC3 puncta. CONCLUSIONS: Acute liver failure is
      accompanied by ongoing fibrosis, HSC activation and autophagy induction.
      Increased HMGB1 activates HSC via autophagy induction. Those findings integrate
      HMGB1, HSCs activation, autophagy into a common framework that underlies the
      fibrosis in ALF.

PMID- 25388427
TI  - Cell growth behaviors of Clostridium acetobutylicum in a pervaporation membrane
      bioreactor for butanol fermentation.
AB  - Acetone-butanol-ethanol fermentation using Clostridium acetobutylicum was studied
      in the continuous and closed-circulating fermentation (CCCF) system. The
      experiment lasting for 192 H was carried out by integrating fermentation with in
      situ pervaporation. In the entire process, the cell growth profile took place in
      the following two phases: the logarithmic phase during early 28 H and the linear
      phase from 130 to 150 H. This was a unique characteristic compared with the curve
      of traditional fermentation, and the fitting equations of two growth phases were
      obtained by Origin software according to the kinetic model of cell growth.
      Besides, the kinetic parameters that include the butanol yield, maximum specific
      growth rate, average specific formation rate, and volumetric productivity of
      butanol were measured as 0.19 g g(-1) , 0.345 H(-1) , 0.134 H(-1) and 0.23 g L(
      1)  H(-1) , respectively. The C. acetobutylicum in the CCCF system showed good
      adaptability and fermentation performance, and the prolonged fermentation period
      and high production were also the main advantages of CCCF technology. 

PMID- 25388428
TI  - Clinical validation of a haplotyping method with next-generation sequencing.

PMID- 25388429
TI  - Circulating tumor DNA as a liquid biopsy for cancer.
AB  - BACKGROUND: Targeted therapies have markedly changed the treatment of cancer over
      the past 10 years. However, almost all tumors acquire resistance to systemic
      treatment as a result of tumor heterogeneity, clonal evolution, and selection.
      Although genotyping is the most currently used method for categorizing tumors for
      clinical decisions, tumor tissues provide only a snapshot, or are often difficult
      to obtain. To overcome these issues, methods are needed for a rapid, cost
      effective, and noninvasive identification of biomarkers at various time points
      during the course of disease. Because cell-free circulating tumor DNA (ctDNA) is
      a potential surrogate for the entire tumor genome, the use of ctDNA as a liquid
      biopsy may help to obtain the genetic follow-up data that are urgently needed.
      CONTENT: This review includes recent studies exploring the diagnostic,
      prognostic, and predictive potential of ctDNA as a liquid biopsy in cancer. In
      addition, it covers biological and technical aspects, including recent advances
      in the analytical sensitivity and accuracy of DNA analysis as well as hurdles
      that have to be overcome before implementation into clinical routine. SUMMARY:
      Although the analysis of ctDNA is a promising area, and despite all efforts to
      develop suitable tools for a comprehensive analysis of tumor genomes from plasma
      DNA, the liquid biopsy is not yet routinely used as a clinical application.
      Harmonization of preanalytical and analytical procedures is needed to provide
      clinical standards to validate the liquid biopsy as a clinical biomarker in well
      designed and sufficiently powered multicenter studies.

PMID- 25388430
TI  - Screening newborn blood spots for 22q11.2 deletion syndrome using multiplex
      droplet digital PCR.
AB  - BACKGROUND: The diagnosis of 22q11 deletion syndrome (22q11DS) is often delayed
      or missed due to the wide spectrum of clinical involvement ranging from mild to
      severe, often life-threatening conditions. A delayed diagnosis can lead to life
      long health issues that could be ameliorated with early intervention and
      treatment. Owing to the high impact of 22q11DS on public health, propositions
      have been made to include 22q11DS in newborn screening panels; however, the
      method of choice for detecting 22q11DS, fluorescent in situ hybridization,
      requires specialized equipment and is cumbersome for most laboratories to
      implement as part of their routine screening. We sought to develop a new genetic
      screen for 22q11DS that is rapid, cost-effective, and easily used by laboratories
      currently performing newborn screening. METHODS: We evaluated the accuracy of
      multiplex droplet digital PCR (ddPCR) in the detection of copy number of 22q11DS
      by screening samples from 26 patients with 22q11DS blindly intermixed with 1096
      blood spot cards from the general population (total n = 1122). RESULTS: Multiplex
      ddPCR correctly identified all 22q11DS samples and distinguished between 1.5- and
      3-Mb deletions, suggesting the approach is sensitive and specific for the
      detection of 22q11DS. CONCLUSIONS: These data demonstrate the utility of
      multiplex ddPCR for large-scale population-based studies that screen for 22q11DS.
      The use of samples from blood spot cards suggests that this approach has promise
      for newborn screening of 22q11DS, and potentially for other microdeletion
      syndromes, for which early detection can positively impact clinical outcome for
      those affected.

PMID- 25388431
TI  - Cardiac troponin testing is overused after the rule-in or rule-out of myocardial
      infarction.

PMID- 25388432
TI  - Synthesis, structures, and properties of crystalline salts with radical anions of
      metal-containing and metal-free phthalocyanines.
AB  - Radical anion salts of metal-containing and metal-free phthalocyanines [MPc(3
      )](.-), where M = Cu(II), Ni(II), H2, Sn(II), Pb(II), Ti(IV)O, and V(IV)O (1-10)
      with tetraalkylammonium cations have been obtained as single crystals by
      phthalocyanine reduction with sodium fluorenone ketyl. Their formation is
      accompanied by the Pc ligand reduction and affects the molecular structure of
      metal phthalocyanine radical anions as well as their optical and magnetic
      properties. Radical anions are characterized by the alternation of short and long
      C-Nimine bonds in the Pc ligand owing to the disruption of its aromaticity. Salts
      1-10 show new bands at 833-1041 nm in the NIR range, whereas the Q- and Soret
      bands are blue-shifted by 0.13-0.25 eV (38-92 nm) and 0.04-0.07 eV (4-13 nm),
      respectively. Radical anions with Ni(II), Sn(II), Pb(II), and Ti(IV)O have S =
      1/2 spin state, whereas [Cu(II)Pc(3-)](.-) and [V(IV)OPc(3-)](.-) containing
      paramagnetic Cu(II) and V(IV)O have two S = 1/2 spins per radical anion. Central
      metal atoms strongly affect EPR spectra of phthalocyanine radical anions. Instead
      of narrow EPR signals characteristic of metal-free phthalocyanine radical anions
      [H2Pc(3-)](.-) (linewidth of 0.08-0.24 mT), broad EPR signals are manifested
      (linewidth of 2-70 mT) with g-factors and linewidths that are strongly
      temperature-dependent. Salt 11 containing the [Na(I)Pc(2-)](-) anions as well as
      previously studied [Fe(I)Pc(2-)](-) and [Co(I)Pc(2-)](-) anions that are formed
      without reduction of the Pc ligand do not show changes in molecular structure or
      optical and magnetic properties characteristic of [MPc(3-)](.-) in 1-10.

PMID- 25388434
TI  - Effects of sitagliptin on blood pressure and heart rate in response to
      intraduodenal glucose infusion in patients with Type 2 diabetes: a potential role
      for glucose-dependent insulinotropic polypeptide?
AB  - AIMS: To evaluate the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin
      on blood pressure and heart rate, measured during a previously reported study, in
      which the effects of sitagliptin during intraduodenal glucose infusion at the
      rate of 2 kcal/min on glucose homeostasis were examined in patients with Type 2
      diabetes. METHODS: A total of 10 people with Type 2 diabetes were studied on two
      different days, 30 min after oral ingestion of sitagliptin (100 mg) or placebo.
      Intraduodenal glucose was infused at 2 kcal/min (60 g over 120 min), and blood
      pressure, heart rate, plasma glucagon-like peptide-1 and glucose-dependent
      insulinotropic polypeptide (total and intact), glucose, insulin and glucagon
      responses were evaluated. RESULTS: In response to intraduodenal glucose infusion,
      heart rate (treatment effect: P = 0.001) and serum insulin concentration
      (treatment * time interaction: P = 0.041) were higher after sitagliptin treatment
      than placebo, without a significant difference in blood pressure, plasma glucagon
      or glucose. During intraduodenal glucose infusion, there was a substantial
      increase in plasma total glucose-dependent insulinotropic polypeptide on both
      days (time effect: P < 0.001), but not in total glucagon-like peptide-1. After
      sitagliptin, plasma intact glucagon-like peptide-1 concentration increased
      slightly (treatment * time interaction: P = 0.044) and glucose-dependent
      insulinotropic polypeptide concentration increased substantially (treatment *
      time interaction: P = 0.003).The heart rate response to intraduodenal glucose was
      related directly to plasma intact glucose-dependent insulinotropic polypeptide
      concentrations (r = 0.75, P = 0.008). CONCLUSIONS: Sitagliptin increased the
      heart rate response to intraduodenal glucose infusion at 2 kcal/min in people
      with Type 2 diabetes, which was associated with augmentation of plasma intact
      glucose-dependent insulinotropic polypeptide concentrations. These observations
      warrant further clarification of a potential role for glucose-dependent
      insulinotropic polypeptide in the control of the 'gut-heart' axis.

PMID- 25388435
TI  - Identification of a selective G-quadruplex DNA binder using a multistep virtual
      screening approach.
AB  - To efficiently identify small molecules binding to a G-quadruplex structure while
      avoiding binding to duplex DNA, we performed a multistep structure-based virtual
      screening by simultaneously taking into account G-quadruplex DNA and duplex DNA.
      Among the 13 compounds selected, one outstanding ligand shows significant
      selectivity for G-quadruplex binding as determined using SPR, FRET-based
      competition and luciferase activity assay. 

PMID- 25388433
TI  - Nfu facilitates the maturation of iron-sulfur proteins and participates in
      virulence in Staphylococcus aureus.
AB  - The acquisition and metabolism of iron (Fe) by the human pathogen Staphylococcus
      aureus is critical for disease progression. S. aureus requires Fe to synthesize
      inorganic cofactors called iron-sulfur (Fe-S) clusters, which are required for
      functional Fe-S proteins. In this study we investigated the mechanisms utilized
      by S. aureus to metabolize Fe-S clusters. We identified that S. aureus utilizes
      the Suf biosynthetic system to synthesize Fe-S clusters and we provide genetic
      evidence suggesting that the sufU and sufB gene products are essential.
      Additional biochemical and genetic analyses identified Nfu as an Fe-S cluster
      carrier, which aids in the maturation of Fe-S proteins. We find that deletion of
      the nfu gene negatively impacts staphylococcal physiology and pathogenicity. A
      nfu mutant accumulates both increased intracellular non-incorporated Fe and
      endogenous reactive oxygen species (ROS) resulting in DNA damage. In addition, a
      strain lacking Nfu is sensitive to exogenously supplied ROS and reactive nitrogen
      species. Congruous with ex vivo findings, a nfu mutant strain is more susceptible
      to oxidative killing by human polymorphonuclear leukocytes and displays decreased
      tissue colonization in a murine model of infection. We conclude that Nfu is
      necessary for staphylococcal pathogenesis and establish Fe-S cluster metabolism
      as an attractive antimicrobial target. 

PMID- 25388436
TI  - Carbon isotope ratios of nandrolone, boldenone, and testosterone preparations
      seized in Norway compared to those of endogenously produced steroids in a Nordic
      reference population.
AB  - Determining the origin of anabolic androgenic steroids (AAS) that also are
      produced endogenously in the human body is a major issue in doping control. In
      some cases, the presence of nandrolone and boldenone metabolites might result
      from endogenous production. The GC-C-IRMS technique (gas chromatography
      combustion-isotope ratio mass spectrometry) enables the carbon isotopic ratio
      (CIR) to be measured to determine the origin of these metabolites. The aim of
      this study was to use GC-C-IRMS to determine the delta(13) CVPDB values of seized
      boldenone and nandrolone preparations to decide if the steroids themselves were
      depleted in (13) C, compared to what is normally seen in endogenously produced
      steroids. In addition, several testosterone preparations were analyzed. A total
      of 69 seized preparations were analyzed. The nandrolone preparations showed
      delta(13) CVPDB values in the range of -31.5 0/00 to -26.7 0/00. The boldenone
      preparations showed delta(13) CVPDB values in the range of -32.0 0/00 to -27.8
      0/00, and for comparison the testosterone preparations showed delta(13) CVPDB
      values of -31.0 0/00 to -24.2 0/00. The results showed that the values measured
      in the nandrolone and boldenone preparations were in the same range as those
      measured in the testosterone preparations. The study also included measurements
      of CIR of endogenously produced steroids in a Norwegian/Danish reference
      population. The delta(13) CVPDB values measured for the endogenous steroids in
      this population were in the range of -21.7 to -26.8. In general, most of the
      preparations investigated in this study show (13) C-depleted delta values
      compared to endogenously produced steroids reflecting a northern European diet.

PMID- 25388437
TI  - The Wax and Wane of Narcissism: Grandiose Narcissism as a Process or State.
AB  - Though grandiose narcissism has predominantly been studied in structural terms
      focused on individuals' general tendencies to be more or less narcissistic-we
      tested whether it also has a meaningful process or state component. Using a daily
      diary study methodology and multilevel modeling (N = 178 undergraduates, 146
      female; Mage  = 18.86, SD = 2.21), we examine whether there is significant
      variability in daily state narcissism and whether this variability relates
      systematically to other psychological states (i.e., self-esteem, stress) and
      daily events. We assessed state narcissism and daily experiences over a 10-day
      period. We observed significant within-person variability in daily narcissism.
      Notably, this variability was not simply random error, as it related
      systematically to other psychological states and daily events. Specifically,
      state narcissism was higher when people experienced more positive agentic
      outcomes (e.g., having power over someone) or more positive communal outcomes
      (e.g., helping someone with a problem). State narcissism was lower on days people
      experienced greater felt stress. These relations held when state self-esteem,
      gender, and trait narcissism were controlled. These findings suggest that
      grandiose narcissism has a meaningful process or state component.

PMID- 25388438
TI  - [Future trend medical apps. From the apps store directly into medical practice?].
AB  - In day to day medical care, patients, nursing staff and doctors currently face a
      bewildering and rapidly growing number of health-related apps running on various
      "smart" devices and there are also uncountable possibilities for the use of such
      technology. Concerning regulation, a risk-based approach is applied for
      development and use (including safety and security considerations) of medical and
      health-related apps. Considering safety-related issues as well as organizational
      matters, this is a sensible approach but requires honest self-assessment as well
      as a high degree of responsibility, networking and good quality management by all
      those involved. This cannot be taken for granted. Apart from regulatory aspects
      it is important to not only consider what is reasonable, helpful or profitable.
      Quality aspects, safety matters, data protection and privacy as well as liability
      issues must also be considered but are often not adequately respected. If
      software quality is compromised, this endangers patient safety as well as data
      protection, privacy and data integrity. This can for example result in unwanted
      advertising or unauthorized access to the stored data by third parties;
      therefore, local, regional and international regulatory measures need to be
      applied in order to ensure safe use of medical apps in all possible areas,
      including the operating room (OR) with its highly specialized demands. Lawmakers
      need to include impulses from all stakeholders in their considerations and this
      should include input from existing private initiatives that already deal with the
      use and evaluation of apps in a medical context. Of course, this process needs to
      respect pre-existing national, European as well as international (harmonized)
      standards. 

PMID- 25388439
TI  - A non-linear beta-binomial regression model for mapping EORTC QLQ- C30 to the EQ
      5D-3L in lung cancer patients: a comparison with existing approaches.
AB  - BACKGROUND: The performance of the Beta Binomial (BB) model is compared with
      several existing models for mapping the EORTC QLQ-C30 (QLQ-C30) on to the EQ-5D
      3L using data from lung cancer trials. METHODS: Data from 2 separate non small
      cell lung cancer clinical trials (TOPICAL and SOCCAR) are used to develop and
      validate the BB model. Comparisons with Linear, TOBIT, Quantile, Quadratic and
      CLAD models are carried out. The mean prediction error, R(2), proportion
      predicted outside the valid range, clinical interpretation of coefficients, model
      fit and estimation of Quality Adjusted Life Years (QALY) are reported and
      compared. Monte-Carlo simulation is also used. RESULTS: The Beta-Binomial
      regression model performed 'best' among all models. For TOPICAL and SOCCAR
      trials, respectively, residual mean square error (RMSE) was 0.09 and 0.11; R(2)
      was 0.75 and 0.71; observed vs. predicted means were 0.612 vs. 0.608 and 0.750
      vs. 0.749. Mean difference in QALY's (observed vs. predicted) were 0.051 vs.
      0.053 and 0.164 vs. 0.162 for TOPICAL and SOCCAR respectively. Models tested on
      independent data show simulated 95% confidence from the BB model containing the
      observed mean more often (77% and 59% for TOPICAL and SOCCAR respectively)
      compared to the other models. All algorithms over-predict at poorer health states
      but the BB model was relatively better, particularly for the SOCCAR data.
      CONCLUSION: The BB model may offer superior predictive properties amongst mapping
      algorithms considered and may be more useful when predicting EQ-5D-3L at poorer
      health states. We recommend the algorithm derived from the TOPICAL data due to
      better predictive properties and less uncertainty.

PMID- 25388440
TI  - Time course change of COX2-PGI2/TXA2 following global cerebral ischemia
      reperfusion injury in rat hippocampus.
AB  - BACKGROUND: Neuroinflammation plays pivotal roles in the progression of cerebral
      ischemia injury. Prostaglandins (PGs) as the major inflammatory mediators in the
      brain participate in the pathophysiological processes of cerebral ischemia
      injury. Cyclooxygenase-2 (COX2) is the rate-limiting enzyme of PGs, and thus it
      is necessary to characterize of the expression patterns of COX2 and its
      downstream products at the same time in a cerebral ischemia/reperfusion (I/R)
      model. METHODS: The levels of prostacyclin (PGI2) and thromboxane (TXA2) and the
      expression of COX2 were detected in the rat hippocampus at different time points
      after reperfusion (30 min, 2 h, 6 h, 24 h, 48 h, 7 d, and 15 d). RESULTS: The
      COX2 mRNA and protein expressions in hippocampus both remarkably increased at 30
      min, and peaked at 7 d after global cerebral I/R compared with the sham-operated
      group. The level of PGI2 significantly increased at 2 h after reperfusion, with a
      peak at 48 h, but was still significantly higher than the sham-operated animals
      at 15 d. TXA2 level decreased at 30 min and 2 h after reperfusion, but
      significantly increased at 6 h and peaked at 48 h. PGI2/TXA2 ratio increased at
      30 min after reperfusion, and peaked at 48 h compared with the sham-operated
      animals. CONCLUSIONS: I/R injury significantly increased the COX2 expression,
      PGI2 and TXA2 levels, and the PGI2/TXA2 ratio in rat hippocampus in a time
      dependent manner. As a consequence, the increased PGI2 level and PGI2/TXA2 ratio
      may represent a physiological mechanism to protect the brain against the neuronal
      damage produced by I/R injury.

PMID- 25388447
TI  - Hematopoietic Stem Cell Transplantation for X-Linked Thrombocytopenia With
      Mutations in the WAS gene.
AB  - X-linked thrombocytopenia (XLT) is a mild form of the Wiskott-Aldrich syndrome
      (WAS) caused by mutations in the WAS gene. A recent retrospective study of the
      clinical outcome and molecular basis of a large cohort of XLT patients
      demonstrated that although overall survival is excellent, event free survival is
      severely affected with conservative treatment. To answer the question whether
      hematopoietic stem cell transplantation (HSCT) offers a viable alternative
      therapeutic option in XLT, we retrospectively investigated the outcome of HSCT in
      a cohort of 24 XLT patients who received HSCT between 1990 and 2011 at 14
      transplant centers in the United States, Italy, Germany, Canada, and Japan. The
      engraftment rate was 100% and the overall survival rate was 83.3%. Of the four
      non-survivors, 2 underwent splenectomy prior to HSCT and died of sepsis, and two
      of aspergillus infections associated with severe GVHD. In all but one patient,
      pretransplant complications were resolved by HSCT. Our data indicate that HSCT
      following myeloablative conditioning is curative and associated with acceptable
      risks as a treatment option for XLT.

PMID- 25388448
TI  - Whole Genome Sequencing Reveals a Chromosome 9p Deletion Causing DOCK8 Deficiency
      in an Adult Diagnosed with Hyper IgE Syndrome Who Developed Progressive
      Multifocal Leukoencephalopathy.
AB  - PURPOSE: A 30 year-old man with a history of recurrent skin infections as well as
      elevated serum IgE and eosinophils developed neurological symptoms and had T2
      hyperintense lesions observed in cerebral MRI. The immune symptoms were
      attributed to Hyper IgE syndrome (HIES) and the neurological symptoms with
      presence of JC virus in cerebrospinal fluid were diagnosed as Progressive
      Multifocal Leukoencephalopathy (PML). The patient was negative for STAT3
      mutations. To determine if other mutations explain HIES and/or PML in this
      subject, his DNA was analyzed by whole genome sequencing. METHODS: Whole genome
      sequencing was completed to 30X coverage, and whole genome SNP typing was used to
      complement these data. The methods revealed single nucleotide variants,
      structural variants, and copy number variants across the genome. Genome-wide data
      were analyzed for homozygous or compound heterozygous null mutations for all
      protein coding genes. Mutations were confirmed by PCR and/or Sanger sequencing.
      RESULTS: Whole genome analysis revealed deletions near the telomere of both
      copies of chromosome 9p. Several genes, including DOCK8, were impacted by the
      deletions but it was unclear whether each chromosome had identical or distinct
      deletions. PCR across the impacted region combined with Sanger sequencing of
      selected fragments confirmed a homozygous deletion from position 10,211 to
      586,751. CONCLUSION: While several genes are impacted by the deletion, DOCK8
      deficiency is the most probable cause of HIES in this patient. DOCK8 deficiency
      may have also predisposed the patient to develop PML.

PMID- 25388449
TI  - Six-year incidence of ocular hypertension in a South Indian population: the
      Chennai eye disease incidence study.
AB  - AIMS: To report the 6-year incidence and risk factors for ocular hypertension
      (OHT) in a population-based study in southern India. METHODS: 6 years after
      baseline evaluation, 56.9% subjects (participants:non-participants, 4421:3353)
      were re-examined at the base hospital. Incident OHT was defined as an intraocular
      pressure above the 97.5th centile for the population with no evidence of glaucoma
      in the 2852 phakic subjects, 40 years or older. Subjects with trauma, laser or
      incisional surgery at baseline or follow-up were excluded (total exclusions:
      1569). RESULTS: Incidence of OHT at 6 years was 62/2852 subjects (2.17% (95% CI
      1.64% to 2.71%, men:women, 36:26)). Incidence was higher in the rural cohort as
      compared with the urban cohort (80.6% vs 19.4%, p<0.001). A higher baseline
      intraocular pressure (with increasing OR: 16-18 mm Hg (OR 4.0, 95% CI 2.1 to
      7.9), 19-21 mm Hg (OR 11.4, 95% CI 5.7 to 22.9), 22-24 mm Hg (OR 42.6, 95% CI
      11.0 to 164.8, in the urban cohort)) and increasing age (50-59 years (OR 1.9, 95%
      CI 1.1 to 3.3), 70 years and above (OR 3.6, 95% CI 1.2 to 10.6)) were
      significantly associated risk factors for incident OHT. CONCLUSIONS: A
      significant proportion of this normal population converted to OHT. A higher
      incidence of conversion was seen in the rural population.

PMID- 25388450
TI  - Development of a microtiter plate-based assay for the detection of lipase
      catalyzed transesterifications in organic solvents.
AB  - A microtiter plate-based assay was developed to evaluate the ability of lipases
      to perform transesterifications when employed in different organic solvents. A 4
      nitrophenol assay was carried out employing seven different lipase formulations
      and two fatty acid methyl esters with different chain lengths in a total of six
      organic solvents with logP values approximately between 1 and -1. This assay
      delivered results within comparatively short times measured by a color reaction
      and thus facilitates the choice of an enzyme-solvent combination for the
      synthesis of glycolipids. To validate the findings, glycolipid syntheses were
      performed using the same lipase formulation in the same solvents. When comparing
      the results obtained using the microtiter plate-based assay to the results of the
      glycolipid syntheses using the same lipases and solvents, matching results were
      obtained. 

PMID- 25388451
TI  - Tissue normalizing capacity as a key determinant of carcinogenesis: an in silico
      simulation.
AB  - A perturbed microenvironment is at the core of carcinogenesis. Here, we used a 2D
      cellular automata model to simulate how cancers are generated in epithelial
      tissue. We applied several mathematical rules to simulate tissue renewal and
      surrounding cell control. Under the simulation, we showed that the average value
      of surrounding normal cells could be an indicator for the tissue normalizing
      capacity (TNC). Further, we found the incidence of carcinogenesis correlated
      inversely with the TNC. Interestingly, we also found that multi-round mutagenesis
      could gradually disturb the TNC when compared to one-round mutagenesis: cancer
      incidence increased significantly compared to one-round mutagenesis. Our model
      suggests that the genetic alterations (mutations) by themselves were not
      sufficient to initiate cancer. The perturbation of TNC could be a key process
      leading to carcinogenesis. 

PMID- 25388452
TI  - Improved stability and efficacy of chitosan/pDNA complexes for gene delivery.
AB  - Among polymeric polycations, chitosan has emerged as a powerful carrier for gene
      delivery. Only a few studies have focused on the stability of the chitosan/DNA
      complex under storage, although this is imperative for nanomedicinal
      applications. Here, we synthesized polyelectrolyte complexes at a charge ratio of
      10 using 50 kDa chitosan and plasmid (p)DNA that encodes a GFP reporter. These
      preparations were stable up to 3 months at 4  degrees C and showed reproducible
      transfection efficiencies in vitro in HEK293 cells. In addition, we developed a
      methodology that increases the in vitro transfection efficiency of chitosan/pDNA
      complexes by 150% with respect to standard procedures. Notably, intracellular
      pDNA release and transfected cells peaked 5 days following transection of
      mitotically active cells. These new developments in formulation technology
      enhance the potential for polymeric nanoparticle-mediated gene therapy.

PMID- 25388453
TI  - Magnetotactic bacteria for cancer therapy.
AB  - Cancer is characterized by anomalous cell growth. Conventional therapies face
      many challenges and hence alternative treatment methods are in great demand. In
      addition, nature offers the best inspiration and recently many therapies of
      natural origin have proved multi-targeted, multi-staged, and a multi-component
      mode of action against cancer. Magnetotactic bacteria and magnetosomes-based
      treatment methods are among them. Present paper reviews various routes by which
      magnetotactic bacteria and magnetosomes contribute to cancer therapy. 

PMID- 25388454
TI  - Rapid detection of 6*-histidine-labeled recombinant proteins by
      immunochromatography using dye-labeled cellulose nanobeads.
AB  - A rapid and easy immunochromatography assay using dye-labeled cellulose nanobeads
      (CNBs) was developed to detect proteins with hexa-histidine tag (His-tag) to
      characterize recombinant proteins during purification. Recombinant ATG8 protein
      was used as a His-tagged protein, and ATG8-conjugated CNBs (A-CNBs) were
      prepared. The original ATG8 in the sample solution competed with A-CNBs for anti
      His-tag antibodies spotted on to the strip resulting in an inverse relationship
      between ATG8 concentration and the colorimetric signal. The usefulness of this
      method was shown by adding ATG8 to a 1% Escherichia coli extract. In addition,
      this assay can be used to detect other His-tagged proteins without protein
      specific antibodies. Because the identification of fractions containing His
      tagged proteins by western blotting or ELISA is labor-intensive and expensive,
      our method provides an efficient and cheaper alternative.

PMID- 25388455
TI  - Spectroscopic approach for dynamic bioanalyte tracking with minimal concentration
      information.
AB  - Vibrational spectroscopy has emerged as a promising tool for non-invasive,
      multiplexed measurement of blood constituents - an outstanding problem in
      biophotonics. Here, we propose a novel analytical framework that enables
      spectroscopy-based longitudinal tracking of chemical concentration without
      necessitating extensive a priori concentration information. The principal idea is
      to employ a concentration space transformation acquired from the spectral
      information, where these estimates are used together with the concentration
      profiles generated from the system kinetic model. Using blood glucose monitoring
      by Raman spectroscopy as an illustrative example, we demonstrate the efficacy of
      the proposed approach as compared to conventional calibration methods.
      Specifically, our approach exhibits a 35% reduction in error over partial least
      squares regression when applied to a dataset acquired from human subjects
      undergoing glucose tolerance tests. This method offers a new route at screening
      gestational diabetes and opens doors for continuous process monitoring without
      sample perturbation at intermediate time points. 

PMID- 25388456
TI  - Primary central nervous system angiosarcoma: a case report and literature review.
AB  - Angiosarcoma is a rare vascular malignant neoplasm that mainly occurs in skin and
      soft tissues. Intracranial localization is very rare and only a few cases have
      been reported. This report intends to present the clinical, radiological and
      pathological pictures of a primary central nervous system angiosarcoma along with
      a review of the literature. A 35-year-old woman presented at our institution with
      weakness and sensory disturbances of her right hand. Neuroimaging revealed a
      roughly round, hemorrhagic and moderately enhancing lesion in the left frontal
      posterior region. The tumor was totally removed under awake anesthesia and
      continuous monitoring of motor and language functions. Histopathology revealed an
      epithelioid angiosarcoma. Radical removal, followed by adjuvant radiotherapy and
      chemotherapy, is able to completely control the disease for a relatively long
      period.

PMID- 25388457
TI  - Chemistry and pharmacology of Angiotensin-converting enzyme inhibitors.
AB  - The renin-angiotensin system has been established as an attractive target for
      pharmacological intervention since the discovery of first angiotensin-converting
      enzyme inhibitors (ACE-Is). In fact, these drugs are primarily used in the
      management of cardiovascular system-related diseases and renal insufficiency.
      Their mechanism of action involves the adjustment of balance between
      vasoconstrictive, hypertrophic and salt/water-retentive angiotensin II and
      vasodilatory and natriuretic bradykinin by the inhibition of angiotensin II
      biosynthesis and bradykinin degradation. Currently there are thirteen family
      members approved for use in humans. They differ in structure, chemistry and
      pharmacokinetic and pharmacodynamic properties yet they display a similar
      pharmacologic and toxicologic profile. All of them are effective in the treatment
      of hypertension as well as in cardiac insufficiency or diabetic nephropathy.
      Although they are generally well-tolerated several serious side-effects including
      life-threatening angioedema, renal failure and persistent dry cough could occur
      during the administration of ACE-Is, which may require the cessation of therapy.
      Furthermore, to provide maximum safety and efficiency of ACE-Is-based therapy,
      the knowledge of the related drug interactions and chronokinetics seems to be an
      absolute requirement. Here we discuss the above-mentioned issues regarding the
      pharmaceutical and chemical properties of the commercially- used ACE-Is. 

PMID- 25388458
TI  - [Opportunities and challenges in the era of personal genome].

PMID- 25388459
TI  - [Analysis of incidence and mortality of thyroid cancer in China, 2010].
AB  - OBJECTIVE: To analysis the incidence and mortality status of thyroid cancer in
      China, 2010. METHODS: Incidence and mortality data of thyroid cancer were derived
      from 145 cancer registries in China of 2010.Incidences, mortality, age-specific
      rates of thyroid cancer in different areas (urban and rural) were calculated. The
      incident cases and deaths were estimated using age-specific rates and national
      population data. Chinese census in 2000 and Segi's population were used for age
      standardized incidence and mortality rates. RESULTS: The registration areas
      covered a total of 158 403 248 population (92 433 739) in urban areas and 65 969
      509 in rural areas, which accounted for 12.05% (158 403 248/1 314 873 293) of the
      total population of the whole country in 2010. The estimates of new cancer
      incident cases was 54 175 (male 12 962, female 41 213), with the crude incidence
      rate of 4.12/100 000 (54 175/1 314 873 293). Age-standardized incidence rates by
      Chinese standard population (ASIRC, 2000) and by world standard population
      (ASIRW) were 3.62/100 000 and 3.23/100 000, respectively, which accounted for
      1.75% (54 175/3 093 039) of all malignant tumors in 2010. Male to female ratio
      was 1: 3.2, the incidence rate in urban areas was 1.46 times higher than that of
      rural areas. The estimates number of cancer deaths was 4 504 (male 1 529 cases
      and female 2 975 cases) in 2010 in China with the crude mortality rate of thyroid
      cancer 0.34/100 000 (4 504/1 314 873 293). Age-standardized mortality rates by
      Chinese standard population (ASIRC, 2000) and by world standard population
      (ASIRW) were 0.27/100 000 and 0.26/100 000, respectively, which accounted for
      0.23% (4 504/1 956 662) of all malignant related deaths. The cumulative incidence
      and mortality rates (0-74 years old) were 0.32% and 0.03%, respectively.
      According to the data from 145 cancer registries, papillary carcinoma was the
      main pathology type, which accounted for 86.0% (6 237/7 253) of all malignant
      tumors. CONCLUSION: The incidence and mortality rates of thyroid cancer in urban
      areas of China were higher than that in rural areas, and females had higher
      incidence rate of thyroid than males. The reasons related the higher incidence
      rate of thyroid cancer in urban China should be paid more attention to in the
      future.

PMID- 25388460
TI  - [Analysis of lymphoma incidence in Beijing, 1998-2010].
AB  - OBJECTIVE: To analyze the incidence trends and characteristics of lymphoma in
      Beijing, 1998-2010. METHODS: Total of 9 763 new cases diagnosed as lymphoma in
      1998-2010 were extracted from the population-based database of Beijing Cancer
      Registry, covering population of 151 601 066 person-years. Incidence, age
      adjusted incidence, cumulative incidence, truncated incidence and annual
      percentage change (APC) were calculated. The gender-specific, age-specific and
      pathology-specific incidence trends were analyzed. RESULT: The incidence rate of
      lymphoma was 6.48/100 000 (9 763/150 720 187) during the period of 1998-2010,
      increased from 3.78/100 000 (410/10 850 626) in 1998 to 8.88/100 000 (1 111/12
      518 114) in 2010 with an increasing rate of 136.17% (APC = 5.21%, P < 0.05). The
      incidence rate of Hodgkin lymphoma increased from 0.25/100 000 (27/10 850 626) in
      1998 to 0.47/100 000 (59/12 518 114) in 2010 with an increasing rate of 88.00%
      (APC = 4.33%, P < 0.05). The incidence rate of non-Hodgkin lymphoma was increased
      from 2.89/100 000 (314/10 850 626) in 1998 to 5.93/100 000 (742/12 518 114) in
      2010 with an increasing rate of 105.19% (APC = 4.19%, P < 0.05) . During the
      period of 1998-2010, the incidence of lymphoma was 7.78/100 000 (7 125/91 621
      898) in urban areas and 4.47/100 000 (2 638/59 098 289) in rural areas, 7.40/100
      000 (5 632/76 121 672) in males and 5.54/100 000 (4 131/74 598 518) in females.
      CONCLUSION: The incidence of lymphoma keeps increasing in 1998-2010, and the
      incidence was higher in males than females, urban areas than rural areas. The
      incidence patterns of Hodgkin lymphoma and non-Hodgkin lymphoma were different.

PMID- 25388461
TI  - [Analysis of cervical cancer incidence and mortality in cancer registries of
      Zhejiang province, 2000 to 2009].
AB  - OBJECTIVE: To investigate the cervical cancer incidence and mortality in cancer
      registries of Zhejiang province during 2000 to 2009. METHODS: The data of
      cervical cancer incidence and mortality were collected from six cancer registries
      in Zhejiang province. Staff of Zhejiang Provincial Cancer Prevention and Control
      Office checked, sorted and analyzed the data to calculate crude, standardized
      rate and trend. Chinese census in 1982 and Segi's population were used for age
      standardized incidence and mortality rates. RESULTS: The incidence rate of
      cervical cancer in Zhejiang cancer registration areas was 11.78/100 000 during
      2000 to 2009, and age-standardized incidence rates by Chinese standard population
      and by world standard population were 7.05/100 000 and 8.62/100 000,
      respectively. The mortality rate was 1.89/100 000, and age-standardized mortality
      rates by Chinese standard population and by world standard population were
      0.95/100 000 and 1.23/100 000, respectively. The age-specific incidence rates
      showed different trends, increased significantly after the age of 25, peaked at
      45-year-old group, which was 23.03/100 000 (578/2 510 099) , and decreased at the
      age of 50, while the age-specific mortality rates gentlely increased, peaked at
      85 years of age group, which was 11.94/100 000 (33/276 414) . The cervical Cancer
      Incidence from 5.96/100 000 (86/1 443 589) in 2000, increased to 18.90/100 000
      (898/4 751 426) in 2009, the annual percent change (APC) was 16.64% (95%CI:11.87%
      21.61%). The mortality showed a gentle upward trend from 1.45/100 000 (21/1 443
      589) , increased to 2.53/100 000 (120/4 751 426) in 2009, the APC was 6.63%
      (95%CI:1.73%-11.77%). CONCLUSION: Cervical cancer showed younger trend, the
      incidence and mortality trends showed an increasing trend, should strengthen the
      prevention and control of cervical cancer.

PMID- 25388462
TI  - [Survival analysis of AIDS patients in Liangshan prefecture, Sichuan province
      from 1995 to 2012].
AB  - OBJECTIVE: To analyze the survival time and its related factors among AIDS
      patients in Liangshan prefecture of Sichuan province from 1995 to 2012. METHODS:
      A retrospective cohort study was conducted to analyze the information of 5 263
      AIDS patients. The data were collected from Chinese HIV/AIDS Comprehensive
      Information Management System. Life table method was applied to calculate the
      survival proportion, and Kaplan-Meier and Cox proportion hazard regression model
      were used to identify the factors related to survival time. RESULTS: Among 5 273
      AIDS patients, 819 (15.6%)died of AIDS related diseases; 2 782(52.9%) received
      antiretroviral therapy. The average survival time was 126.7 (117.1-136.2) months,
      and the survival rate in 1, 5, 10, 15 years were 95.4%, 78.8%, 54.2%, and 31.8%
      respectively. Univariate analysis showed a significant difference in survival
      time of age diagnosed as AIDS patients, nationality, transmission route, AIDS
      phase, CD4(+)T cell counts in the last testing, receiving antiretroviral therapy
      or not. Multivariate Cox regression showed age diagnosed AIDS below 50 years old
      ( < 15 years old:HR = 0.141, 95%CI:0.036-0.551;15-49 years old:HR = 0.343,
      95%CI:0.241-0.489), HIV infection diagnosed phase (HR = 0.554, 95%CI:0.432
      0.709), CD4(+)T cell counts last testing >= 350/ul (HR = 0.347, 95%CI:0.274
      0.439) reduced the risk of dying of AIDS related diseases among AIDS patients.
      The patients having not received antiretroviral therapy had a higher risk of
      death(HR = 3.478, 95%CI:2.943-4.112) compared to those who received
      antiretroviral therapy. CONCLUSION: Survival time of AIDS patients was possibly
      mainly influenced by the age of diagnosed as AIDS patients, AIDS phase, CD4(+)T
      cell counts and whether or not received antiretroviral therapy. The early
      initiation of antiretroviral therapy could extend the survival time.

PMID- 25388463
TI  - [A follow-up study of HIV long-term non-progress populations in Henan province].
AB  - OBJECTIVE: To explore the related testing indicators variation of HIV long-term
      non-progress populations. METHODS: The long-term non-progress populations in some
      areas of Henan were recruited, and the study was carried out according to
      different CD4(+)T lymphocytes counts for two groups. The dynamic characteristics
      of immune status and viral load between LTNP-1group (CD4(+)T lymphocytes >=
      500/ul, 42 cases) and LTNP-2 group(350/ul <= CD4(+)T lymphocytes < 500/ul, 49
      cases) from July 2010 to August 2013 were observed. The characteristics of HIV
      elite controllers during the follow-up were also described. RESULTS: LTNP were
      recruited, 56% (51 cases) were men, and 44% (40 cases) were women. The study
      population were aged from 38 to 65 years old. A total of 320 individuals were
      followed-up, 14 cases were lost, 2 deaths, and 16 cases had received
      antiretroviral therapy during four years. To analyze the annual changes of
      CD4(+)T lymphocytes and VL of the group from 2010 to 2013, LTNP-1 group CD4(+)T
      lymphocytes from 654.0(545.2-809.5) decreased to 494.0(341.0-574.7), and LTNP-2
      group decreased from 493.0 (429.5-770.0) to 343.5(253.0-500.8), CD4(+)T
      lymphocytes decline of over times of two groups in longitudinal analysis (chi(2)
      = 50.32, P < 0.01; chi(2) = 31.03, P < 0.01). lg (VL) of LTNP-1 group were 3.52
      (3.15-4.27), 3.71 (2.70-4.55), 3.86 (3.59-4.55), 3.96 (3.25-4.36), and lg (VL) of
      TNP-2 group were 4.35 (3.72-4.83), 4.35 (3.97-4.94), 4.71 (3.96-4.95), 5.04(4.78
      5.26), respectively (P > 0.05). The same year inter-group comparison found
      CD4(+)T lymphocytes of LTNP-1 group were higher than LTNP-2 group (Z = 5.23, P <
      0.01; Z = 3.06, P < 0.01; Z = 2.51, P < 0.05; Z = 2.47, P < 0.05). VL of LTNP-2
      group increased from 4.35(3.97-4.94) to 5.04 (4.78-5.26) during 2011 to 2013,
      were higher than LTNP-1 group in the same year (Z = 2.28, P < 0.05; Z = 2.58, P <
      0.05; Z = 2.76, P < 0.05). 65 cases HCV antibody were positive in 91 individuals,
      and the HCV antibody positive rate was 76% (32/42), 67% (33/49) between LTNP-1
      group and LTNP-2 group. Six elite controllers maintained CD4(+)T lymphocytes >=
      500/ul, VL<1 000 copies/ml during four years follow-up. CONCLUSION: The long-term
      non-progress populations in Henan were overall healthy, and VL were relatively
      stable, there was a decreased trend of CD4 year by year, and HCV co-infection
      rate was high.

PMID- 25388464
TI  - [Study on the prevalence of loss to follow-up and risk factors among human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients
      in Baoshan city, Yunnan province].
AB  - OBJECTIVE: To determine the prevalence of loss to follow-up (PLF) and risk
      factors among human immunodeficiency virus (HIV)/acquired immunodeficiency
      syndrome (AIDS) patients from 1989 to 2012 in Baoshan city, Yunnan province.
      METHODS: The epidemic and follow-up databases of HIV/AIDS patients by the end of
      2012 were downloaded from "the history card downloading site" of HIV/AIDS
      database in China Information System for Disease Control and Prevention and
      obtained the related data of patients from 1989 to 2012 who had local residence
      in Baoshan city. These data included demographic characteristics (genders, age at
      the time of HIV testing positive, and occupation, marital status, and education
      levels, et al), transmission routes, and disease staging, antiretroviral therapy
      (ART), and sources of samples, the first CD4(+)T cell counts, and status of
      follow-up, et al. Descriptive epidemiological study was used to describe the
      general characteristics of loss to follow-up. Multivariable Cox regression was
      used for determining risk factors associated with loss to follow-up. RESULTS: A
      total of 3 295 eligible HIV/AIDS patients from 1989 to 2012 were included. The
      accumulative study person-year was 11 416.59 years, 222 HIV/AIDS patients were
      lost to follow-up, and the PLF was 0.019 4/ person years (py). The highest PLF
      was 0.052 8/py in 2008, the lowest was 0.006 2/py in 2012. The lost patients
      included 56.76% (126/222) males and 43.24% (96/222) females, the PLFs were 0.020
      4/py, 0.018 3/py, respectively. Baoshan city, other cities in Yunnan province,
      and other provinces, foreign nationality as the family register reached 53.60%
      (119/222) , 28.83% (64/222) , and 5.86% (13/222) , 11.71% (26/222) ,
      respectively, and their PLFs were 0.012 5/py, 0.046 3/py, and 0.053 6/py, 0.095
      6/py, respectively. Receiving ART and not receiving ART occupied 6.76% (15/222) ,
      93.24% (207/222) , respectively, and the PLFs were 0.001 9/py, 0.0588/py. AIDS
      and HIV staging standed at 8.11% (18/222) , 91.89% (204/222) , respectively, and
      the PLFs were 0.003 3, 0.034 5/py. The first CD4(+)T cell counts < 200, 200-350,
      and > 350 cells /ml accounted for 4.95% (11/222) , 73.87% (164/222) , 21.17%
      (47/222) , respectively, and the PLFs were 0.004 8/py, 0.024 0/py, 0.020 3/py.
      The results of multivariable Cox regression showed the risks of loss to follow-up
      (RLFs) of family register as other cities in Yunnan province (HR = 3.11,
      95%CI:2.28-4.25) , other provinces (HR = 2.55, 95%CI:1.42-4.56) , and foreign
      nationality (HR = 2.12, 95%CI:1.35-3.33) higher than that of Baoshan city,
      respectively. The RLFs of not receiving ART (HR = 20.83, 95%CI:11.74-36.96) and
      HIV staging (HR = 3.61, 95%CI:1.82-7.16) were higher than those of receiving ART
      and AIDS staging, respectively, moreover, the RFLs of the first CD4(+)T cell
      counts between 200-350 cells/ml (HR = 0.35, 95%CI:0.15-0.82) and the first
      CD4(+)T cell counts > 350 cells/ml (HR = 0.29, 95%CI:0.12-0.72) were less than
      that of first CD4(+)T cell counts < 200 cells /ml, respectively. The RLF of
      transmission route as injecting drug (HR = 0.60, 95%CI:0.41-0.88) was less than
      that of heterosexual contact. CONCLUSION: Overall, the prevalence of loss to
      follow-up among HIV/AIDS patients shows a downward trend, moreover, patients of
      outsiders, heterosexual contact, HIV staging, baseline CD4(+)T cell counts < 200
      cells/ml are at higher risk of loss to follow-up.

PMID- 25388465
TI  - [Estimation of syphilis epidemic through application of workbook method among
      populations aged from 15 to 49 years old in China in 2011].
AB  - OBJECTIVE: To apply workbook method for the estimation on syphilis epidemic in
      China. METHODS: The data on population size and syphilis infection were collected
      by national STD and HIV/AIDS surveillance system among six populations aged from
      15 to 49 years old in 31 provinces in 2011. Six groups included female sex
      workers (FSW), men who have sex with men (MSM), STD clinic attendee, drug users,
      pregnant women and general population. Meta analysis was applied to pool the
      different prevalence of the same population in the different sentinels of each
      province, and then workbook method was applied to estimate the syphilis epidemic
      in China. RESULTS: The estimation of syphilis epidemic(95%CI) was 2 979 422(1 504
      000-6 063 309) among the populations aged 15 to 49 years old in 2011. The
      estimation among FSW was 54 624 (38 422-78 875) , that of MSM was 265 453 (162
      586-506 520) , that of STD clinic attendee was 53 555 (31 256-98 057) , that of
      drug users was 94 244 (66 475-139 349) , that of pregnant women was 70 062 (39
      942-136 584) and that of general population was 2 441 484 (1 165 319-5 103 924) .
      The proportion of general population in the whole estimation of syphilis
      infection was 81.94%, and that of MSM was 8.91%. The estimation of syphilis
      incidence was 1 489 711 among 15 to 49 years old, and the estimation of syphilis
      prevalence was 0.40% in the whole country. The estimation of incidence in this
      research was 5.2 times as the number of reported cases from China information
      system for diseases control and prevention. CONCLUSION: Workbook method was a
      scientific and feasible toolkit for the estimation of syphilis epidemic in China,
      and the estimation outcomes were greatly significant for syphilis control.

PMID- 25388466
TI  - [Epidemiological characteristics of Salmonella in animal source foods in Hunan].
AB  - OBJECTIVE: To study the molecular epidemiological characteristics of Salmonella
      in animal source foods in Hunan. METHODS: The fair trade markets and supermarkets
      of ten cities were chosen to sample animal source foods for isolating Salmonella
      in Hunan province in 2010. A total of 692 samples were collected by aseptic
      sampling, included 159 livestock meats, 152 poultry meats, and 381 aquatic
      products.Salmonella strains isolated were subjected to stereotyping,
      antimicrobial susceptibility testing and pulsed field gel electrophoresis (PFGE).
      RESULTS: Salmonella was detected in 93 of 692 animal food samples with the
      detection rate of 13.4%. The detection rates of Salmonella in poultry meats,
      livestock meats and aquatic products were 23.0% (35/152), 22.6% (36/159) and 5.8%
      (22/381) respectively. Therefore, the detection rate in aquatic products was
      lower than that of poultry meats and livestock meats (chi(2) = 33.86, P < 0.05;
      chi(2) = 33.29, P < 0.05, respectively). The serotypes of isolates showed
      diversity, and Salmonella Derby (33/94, 35.1%) was the predominant
      serotypes.79.8% (75/94) strains showed resistant to more than one antibiotic used
      in the test, 31.9% (30/94) strains showed resistant to more than 5 antibiotics. A
      significant difference was observed for multidrug resistance between Salmonella
      isolated from poultry (47.2%, 17/36) and livestock meats (22.2%, 8/36) (chi(2) =
      4.96, P < 0.05). And the highest resistant rate was found in tetracycline, as
      high as 62.8% (59/94). All the strains were divided into 69 PFGE
      subtypes.Furthermore the dominating subtypes were type 7 (6 strains), type 15 (4
      strains), type 22 (6 strains). CONCLUSION: Inspection results showed that
      Salmonella contamination in animal source foods were serious in Hunan province,
      and the isolates expressed high level resistance to the antibiotics.Furthermore
      the PFGE results indicated that there were epidemic strains of Salmonella in
      Hunan.

PMID- 25388467
TI  - [Evaluation of the feeding status of infants and young children under 2 years old
      in rural areas of Hubei province].
AB  - OBJECTIVE: To evaluate the current feeding status of infants and young children
      under 2 years old in rural areas of Hubei province. METHODS: The study was
      conducted by cluster random sampling from September 2009 to march 2010. The data
      on breastfeeding and complementary food supplement of the 1 197 infants and young
      children aged 0-23 months in 8 counties of Hubei province were collected through
      questionnaires. The feeding status was analyzed according to the WHO 2008 edition
      of Indicators for assessing infant and young child feeding practices. RESULTS: A
      total of 1 197 children aged 0-23 months were investigated. The rate of ever
      breastfeeding of children aged 0-23 months reached up to 93.9% (1 124/1 197),
      while the percentage of early initiation of breastfeeding was only 22.0% (263/1
      197). The rates of exclusive breastfeeding under 6 months, continued
      breastfeeding for 1 year, and continued breastfeeding for 2 years were 72.1%
      (277/384), 17.0% (26/153) and 4.9% (7/144), respectively. The median time of
      giving complementary food was the 6th month and the weaning time was the 9th
      month. The rate of complementary food supplemented from 6th-8th month in time was
      61.8% (444/718) . The rates of minimum dietary diversity, minimum meal frequency,
      minimum acceptable diet, and consumption of iron-rich or iron-fortified foods
      among children aged 6-23 months were 61.7% (502/813), 81.5% (663/813), 54.4%
      (442/813) and 50.1% (407/813), respectively. CONCLUSION: Late initiation of
      breastfeeding, non-continued breastfeeding, giving complementary food too early
      or too late, inadequate category and frequency of complementary food, and the low
      rate of consumption of iron-rich or iron-fortified foods were the main issues to
      be concerned on infant feeding in rural areas of Hubei province.

PMID- 25388468
TI  - [Evaluation on the status quo of self monitoring of blood glucose and self
      efficacy of diabetes patients in community].
AB  - OBJECTIVE: To investigate the status quo and influence factors of self monitoring
      of blood glucose (SMBG) and self-efficacy of diabetes patients' that participated
      in community diabetes self management group. METHODS: Beijing, Shanghai,
      Chongqing, Jiangsu, Guangdong, and Zhejiang were selected as the study sites
      considering patients management experiences they had. 1 401 adult diabetes
      patients were recruited from communities via health records system screening,
      telephone notification, poster advertisement, letters invitation ways. Face to
      face questionnaire survey was applied to obtain patients' general information,
      diabetes history, diabetes knowledge awareness, SMBG, and self-efficacy
      information. Multiple linear regression was used to analyze the relationship
      between factors and self efficacy. RESULTS: There were 519 male patients (37.0%)
      and 882 female patients (63.0%) with an average age of (64.9 +/- 8.9) years old.
      Patients lived in city accounted for 48.0% (672/1 401) and rural patients
      accounted for 52.0% (729/1 401). Patients who conducted SMBG accounted for 79.9%
      (1 120/1 401) and 33.3% (446/1 401) patients conducted blood glucose monitoring 1
      3 times per month. Rural patients, primary school educated, and new rural
      cooperative medical system (NCMS) covered patients had a higher proportion of
      never conducting SMBG which were 21.9% (160/729), 24.2% (160/662), and 26.3%
      (125/475) , respectively. Scores of self-efficacy was (69.24 +/- 16.30) (hundred
      mark system) with a relative lower score in monitoring of blood glucose (64.09 +/
      20.08) and foot care (63.63 +/- 21.40), as well as a highest score in taking
      medicine and insulin injections (76.10 +/- 22.00). Multiple regression analysis
      on self-efficacy and its related factors show a negative correlation between
      patients' place of residence and self-efficacy (beta' = -0.076) and a positive
      correlation between education and self-efficacy (beta' = 0.114) as well as
      between diabetes knowledge awareness and self-efficacy (beta' = 0.193)(t = -2.46,
      3.71, 7.18, P < 0.05). CONCLUSION: Community diabetes patients had a low self
      efficacy and it was even lower among low economic and education degree patients.
      The worst parts were SMBG and foot care. Place of residence, education, and
      diabetes knowledge awareness are factors that influence patients' self efficacy.

PMID- 25388469
TI  - [Association of health literacy with health management among diabetics].
AB  - OBJECTIVE: To understand status of health literacy among diabetics and their
      health management behaviors, and analyze the relationship of health literacy and
      health management. METHODS: A two-staged cluster randomized sampling method was
      used to investigate 1 130 diabetics in Beijing, Ningbo and Xiamen from October to
      November in 2012. All participants should be diagnosed by primary hospital and
      above and have lived in the community over six months. Diabetic patients who
      indicated that they had severely impaired vision or cognitive disorder, or had
      severe physical deterioration, or did not live in the address provided were
      excluded. A total of 1 130 questionnaires were sent out and 1 083 eligible
      questionnaires were taken back, accounting for 96.87%. Multivariate logistic
      regression was adopted to analyze the association between health literacy and
      health management behaviors and blood glucose level. RESULTS: Among those
      participants, 47.7% (517) were men, 52.3% (566) were women, the age was (67.0 +/-
      9.5). According to diabetes health literacy scores, 73.7% (798/1 083) of them
      were classified as poor health literacy and 26.1% (283/1 083) as essential health
      literacy. Health literacy was associated with health management behaviors
      independently, demonstrating that the probability of utilizing health education,
      free physical examination, lifestyle guidance, monitoring blood glucose on their
      own, measuring blood glucose more than once a week and taking hypoglycemic agent
      regularly among diabetics with essential health literacy were 1.40 (95%CI:1.03
      1.91), 1.65 (95%CI: 1.19-2.28), 2.70 (95%CI:1.98-3.69), 2.05 (95%CI:1.34-3.15),
      2.56 (95%CI:1.85-3.56) , 1.48 (95%CI:1.07-2.06) times of those in diabetics with
      poor health literacy (P < 0.05). CONCLUSION: Health literacy may affect health
      management behaviors among diabetics. More activities targeted on diabetics with
      low health literacy were suggested to improve their' health literacy and their
      skills about diabetes mellitus management.

PMID- 25388470
TI  - [Investigation of the action mechanisms of poly-ADP-ribosylation in hexavalent
      chromium induced cell damage].
AB  - OBJECTIVE: To investigate the effect of poly-ADP-ribosylation in hexavalent
      chromium Cr(VI) induced cell damage. METHODS: The study object, poly (ADP-ribose)
      glycohydrolase (PARG) deficient human bronchial epithelial cells (16HBE cells),
      was constructed previously by our research group. Normal 16HBE cells and PARG
      deficient cells were treated with different doses of Cr (VI) for 24 h to compare
      the differences to Cr (VI) toxicity, meanwhile set up the solvent control group.
      On this basis, 5.0 umol/L of Cr (VI) was selected as the exposure dose, after the
      exposure treatment, total proteins of both cells were extracted for two dimension
      fluorescence difference gel electrophoresis (2D-DIGE) separation, statistically
      significant differential protein spots were screened and identified by matrix
      assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF
      MS/MS), and further validated by Western blot. RESULTS: After Cr (VI) treatment,
      the survival rate of PARG-deficient cells was higher than normal 16HBE cells.
      When the doses reached up to 5.0 umol/L, the survival rate of 16HBE cells and
      PARG-deficient cells were respectively (59.67 +/- 6.43)% and (82.00 +/- 6.25)%,
      the difference between which was significant (t = -4.32, P < 0.05). 18 protein
      spots were selected and successfully identified after 2D-DIGE comparison of
      differential proteins between normal 16HBE cells and PARG-deficient cells before
      and after exposure. The function of those proteins was involved in the
      maintenance of cell shape, energy metabolism, DNA damage repair and regulation of
      gene expression. The differential expression of cofilin-1 was successfully
      validated by Western blot. The expression level of cofilin-1 in the 16HBE cells
      increased after Cr (VI) exposure with the relative expression quantity of 1.41 +/
      0.04 in treated group and 1.00 +/- 0.01 in control group, the difference of
      which was statistically significant (t = -18.00, P < 0.05), while the expression
      level in PARG-deficient cells had no statistically significant difference (t = 
      8.61, P > 0.05). CONCLUSION: Most of the identified differential proteins are
      closely related to tumorigenesis, suggesting that poly-ADP-ribosylation reaction
      may resist the cytotoxicity of Cr(VI) by inhibiting Cr (VI) induced
      tumorigenesis, which provides important reference data to clarify the mechanisms
      of poly-ADP-ribosylation in Cr (VI) induced cell damage.

PMID- 25388471
TI  - [Heat effect stability of inactivated enterovirus 71 vaccine].
AB  - OBJECTIVE: To investigate the effect of temperature on the stability of
      intermediate and final products of inactivated enterovirus 71 vaccine, which was
      prepared in human diploid cells. METHODS: The different batches of harvest viral
      cultures, the vaccine stock solutions and the final productions of inactivated
      enterovirus 71 vaccine were stored at different temperatures. The samples of
      viral culture stored at -20 degrees C or 4 degrees C were harvested at 0, 6, 12
      and 24 months later. The samples of vaccine stock solutions stored at -20 degrees
      C were harvested at 0, 6, 12 and 24 months later, and that stored at 4 degrees C
      were harvested at 0, 1, 3, 6 and 12 months later. The samples of finial products
      were harvested at different time points (0, 6, 12 and 24 months for storing at 4
      degrees C; 0, 7, 14, 28, 42 and 60 d for storing at 25 degrees C; 0, 3, 7, 14 and
      21 d for storing at 37 degrees C). The viral titer, antigen content, antigen
      purity, endotoxin content, effectiveness, pH and appearance of samples were
      determined, respectively. A total of 1 800 BLAB/c mice were immunized by vaccine
      and 150 control mice were injected by diluents without antigen via
      intraperitoneal. The tail vein blood (500 ul per mouse) from 1 950 mice were
      harvested after 4 weeks post injected. The neutralization antibody titers of the
      serum were tested to calculate the half effective dose (ED50) of final products.
      All results were analyzed using analysis of variance to compare the differences
      of the above indexes. RESULTS: The viral titers of harvest viral culture of
      inactivated EV71 vaccine were (6.67 +/- 0.13), (6.56 +/- 0.09), (6.52 +/- 0.04),
      (6.39 +/- 0.16) lgCCID50/ml (CCID50, the half cell culture infective dose) after
      0, 6, 12 and 24 months storage at -20 degrees C; and (6.67 +/- 0.13), (6.41 +/-
      0.13), (6.19 +/- 0.18), (5.97 +/- 0.09) lgCCID50/ml at 4 degrees C. The viral
      titers reduced with time (F = 9.81 or 44.16, P < 0.05). The antigen contents of
      the vaccine stock solution were maintained at (3 626.67 +/- 1 382.56) EU/ml
      within 3 months at 4 degrees C, but were (2 080.00 +/- 876.36), (951.17 +/-
      346.35) EU/ml at 6 and 12 months, respectively. The ED50 of the final production
      were (31.00 +/- 2.71), (32.93 +/- 3.22), (39.37 +/- 3.44) and (46.04 +/- 3.25)
      EU/ml after 0, 6, 12 and 24 months storage at 4  degrees C, but were (31.00 +/-
      2.71), (32.23 +/- 2.66), (34.70 +/- 1.77), (40.04 +/- 2.10), (47.78 +/- 1.93) and
      (56.97 +/- 0.50) EU/ml at 0, 7, 14, 28, 42 and 60 days at 25 degrees C, and were
      (31.00 +/- 0.00), (36.20 +/- 0.00), (41.87 +/- 0.50), (53.25 +/- 0.50) and (64.84
      +/- 0.58) EU/ml at 0, 3, 7, 14 and 21 days at 37 degrees C, respectively. The
      ED50 had increased with the time by and had significantly differences compared
      with the beginning level (F = 28.49, 215.15 or 156.12, P < 0.05). CONCLUSION:
      There is a good stability of the intermediate and final productions of
      inactivated enterovirus 71 (EV71) vaccines, within 24 months at -20 degrees C or
      6 months at 4 degrees C storage for viral culture, 24 months at -20 degrees C or
      3 months at 4 degrees C storage for stock solution and 24 months at 4 degrees C
      or 28 d at 25 degrees C or 7 d at 37 degrees C storage for finial vaccine.

PMID- 25388472
TI  - [Study on detection of Salmonella in poultry samples by real-time PCR with Taqman
      probes].
AB  - OBJECTIVE: To develop a RT-PCR method for a rapid and sensitive detection of
      Salmonella in poultry samples. METHODS: The RT-PCR method was established and its
      specificity was testified on the basis of invA gene. Serial 10-fold diluted pure
      suspension culture of CMCC 50041 was detected by RT-PCR, the standard curve was
      constructed and the amplification efficiency was calculated. Artificially
      contaminated experiment was done, six artificially-inoculated samples containing
      final concentration of Salmonella CMCC 50041 (1, 10, 10(2), 10(3), 10(4), 10(5)
      and 10(6) CFU per 25 g poultry samples) were prepared respectively. All the
      samples were incubated for 0, 4, 8, 12 and 18 h and the DNA was extracted for RT
      PCR detection, meanwhile by PCR detection and the traditional method. The
      sensitiveness and specificity were compared among the three methods. At the same
      time, 16 samples of retail whole poultry were collected from markets and detected
      by the above three methods as well, and thereby to further compare the positive
      detection among the three methods. RESULTS: The established RT-PCR method was
      specific for the detection of Salmonella. The sensitivity was 5.2*10(3) CFU/ml
      for pure Salmonella culture without enrichment. Correlation coefficients of
      standard curves constructed using the Ct versus log value of concentration of
      Salmonella showed good linearity over a 8-log dynamic range (5.2*10(3)-5.2*10(10)
      CFU/ml), with the R(2) at 0.999. RT-PCR detection limit for artificially
      contaminated samples after enriching for 12 h was 1 CFU/25 g sample, which was
      the same with the limit of PCR and 10 times more sensitive than the limit of
      traditional method. Standard curve of sample after enrichment for 12 h was
      established. Seven of 16 samples were detected positive by RT-PCR, which were
      also tested positive by PCR, while only five samples were positive by traditional
      method. The positive ones were quantitatively analyzed using standard curve of
      sample and determined the initial Salmonella numbers of CFU/25 g. CONCLUSION: The
      established RT-PCR technology was simple, rapid, sensitive and specific, which
      was suitable to quickly detect Salmonella in poultry samples.

PMID- 25388473
TI  - Heterotrophic growth of microalgae: metabolic aspects.
AB  - Microalgae are considered photoautotrophic organisms, however several species
      have been found living in environments where autotrophic metabolism is not
      viable. Heterotrophic cultivation, i.e. cell growth and propagation with the use
      of an external carbon source under dark conditions, can be used to study the
      metabolic aspects of microalgae that are not strictly related to photoautotrophic
      growth and to obtain high value products. This manuscript reviews studies related
      to the metabolic aspects of heterotrophic grow of microalga. From the
      physiological and metabolic perspective, the screening of microalgal strains in
      different environments and the development of molecular and metabolic engineering
      tools, will lead to an increase in the number of known microalgae species that
      growth under strict heterotrophic conditions and the variety of carbon sources
      used by these microorganisms. 

PMID- 25388474
TI  - Contribution to the aroma of white wines by controlled Torulaspora delbrueckii
      cultures in association with Saccharomyces cerevisiae.
AB  - Although the positive role of non-Saccharomyces yeasts on the overall quality of
      wine is encouraging research into their oenological potential, current knowledge
      on the topic is still far from satisfactory. This work analyzes the contribution
      of starter cultures of Torulaspora delbrueckii, inoculated sequentially with
      Saccharomyces cerevisiae (multi-starter fermentation), on the fermentation and
      aromas of two different white style wines, i.e., dry and sweet wines. Chemical
      analysis of Soave and Chardonnay wines (dry wines) showed that multi-starter
      fermentation greatly affected the content of several important volatile
      compounds, including 2-phenylethanol, isoamyl acetate, fatty acid esters, C4-C10
      fatty acids and vinylphenols. Moreover, strain-specific contributions have been
      shown by testing two different T. delbrueckii strains. Evidence of the positive
      impact of T. delbrueckii activity on wine quality was also demonstrated in Vino
      Santo, a sweet wine. Due to its low production of acetic acid, this non
      Saccharomyces yeast is recommended for the fermentation of high sugar grapes. T.
      delbrueckii also influenced the content of different variety of chemical groups,
      including lactones. From a sensory perspective, all wines produced by multi
      starter fermentation have greater aromatic intensity and complexity than wines
      resulting from a monoculture fermentation. These results emphasize the potential
      of employing T. delbrueckii, in association with S. cerevisiae, for the
      production of white wines of different styles with improved and enhanced flavour.

PMID- 25388476
TI  - Human antigen R: A novel therapeutic target for diabetic nephropathy?

PMID- 25388475
TI  - Molecular cloning and characterization of a thermostable lipase from deep-sea
      thermophile Geobacillus sp. EPT9.
AB  - A gene (1,254 bp) encoding a lipase was identified from a deep-sea hydrothermal
      field thermophile Geobacillus sp. EPT9. The open reading frame of this gene
      encoded 417 amino acid residues. The gene was cloned, overexpressed in
      Escherichia coli, and the target protein was purified to homogeneity. The
      purified recombinant enzyme presented a molecular mass of 44.8 kDa. When p
      nitrophenyl palmitate was used as a substrate, the recombinant lipase was
      optimally active at 55  degrees C and pH 8.5. The recombinant enzyme retained 44
      % residual activity after incubation at 80  degrees C for 1 h, which indicated
      that Geobacillus sp. EPT9 lipase was thermostable. Homology modeling of strain
      EPT9 lipase was developed with the lipase from Bacillus sp. L2 as a template. The
      core structure exhibits an alpha/beta-hydrolase fold and the typical catalytic
      triad might consist of Ser142, Asp346, and His387. The enzymatic activity of EPT9
      lipase was inhibited by addition of phenylmethylsulfonyl fluoride, indicating
      that it contains serine residue, which plays an important role in the catalytic
      mechanism.

PMID- 25388477
TI  - Palliation for refractory anal fistula--an honorable respite.

PMID- 25388478
TI  - In vitro effects of some flavones on human pyruvate kinase isoenzyme M2.
AB  - PKM2 is an important target for designing anticancer drug. Inhibitors and
      activators of this enzyme are suitable molecules for use in treating cancer. The
      aim of the present study was to investigate the effect of certain flavones on
      PKM2. Apigenin, wogonin, flavone, 3-hydroxyflavone, 5-hydroxyflavone, 6
      hydroxyflavone, and 7-hydroxyflavone effectively inhibited PKM2, with IC50 in the
      range of 0.99-2.120 MUM. The kinetic study indicated that these compounds acted
      as noncompetitive with Ki values of 3.53-5.67 MUM toward phosphoenolpyruvate.
      Scutellarin and tangeritin demonstrated strong activation effect with AC50 values
      < 2 MUM. Diosmetin, baicalin, baicalein, and luteolin showed an intermediate
      level activator effect. These results demonstrate that flavone and their analogs
      could serve as leading compounds to develop new potent and selective inhibitor
      and activator for PKM2. 

PMID- 25388479
TI  - Pulmonary function of a paediatric cohort of patients with postinfectious
      bronchiolitis obliterans. A long term follow-up.
AB  - BACKGROUND: Postinfectious bronchiolitis obliterans (BO) is a chronic respiratory
      disease that usually follows a severe adenovirus infection. OBJECTIVE: To
      determine the evolution of pulmonary function and clinical outcome of children
      with postinfectious BO during childhood. METHODS: The study included patients
      diagnosed with postinfectious BO in whom at least two spirometries were performed
      within a minimum interval of 3 months. RESULTS: 46 met the inclusion criteria.
      The mean (+/-SD) follow-up period was 12.5 (+/-3.5) years. 197 spirometries and
      41 plethysmographies were performed. Initial (9+/-3 years old) lung function was
      as follows (z score, mean+/-SD): forced vital capacity (FVC) -3.8+/-1; forced
      expiratory volume in 1 s (FEV1) -4.4+/-1; FEV1/FVC -2.2+/-1; forced expiratory
      flow (FEF)(25-75) -3.7+/-1; total lung capacity (TLC) 120+/-26%; residual volume
      (RV) 309+/-108%; and RV/TLC 55+/-13. During childhood, FVC and FEV1 increased by
      a mean of 11%/year (95% CI 9.3% to 12.6%; p<0.0001) and 9%/year (95% CI 7.7% to
      10.2%; p<0.0001), and the FEV1/FVC ratio decreased by 1.9%/year (95% CI 1% to
      2.8; p<0.001). The z score for FVC, FEV1 and FEV1/FVC decreased by 0.07 z
      score/year (95% CI 0.1 to 0.01; p<0.05), 0.09 z score/year (95% CI 0.1 to 0.05;
      p<0.01) and 0.04 z score/year (95% CI 0.09 to 0.001; p<0.02), respectively.
      During the follow-up period, 69% of patients required at least one hospital
      readmission and five required mechanical ventilation. Nine patients developed a
      thoracic deformity, and seven whose bronchiectasis did not respond to clinical
      treatment underwent a lobectomy. CONCLUSIONS: After a 12 year follow-up period,
      pulmonary function remained severely impaired, showing an obstructive pattern
      with air trapping that slowly improved during childhood. An unequal growth of
      lung parenchyma over the airways suggests dysinaptic growth. Patients required
      frequent readmission due to recurrent respiratory infections, and hypoxaemia
      improved slowly over time.

PMID- 25388480
TI  - An evaluation of combat application tourniquets on training military personnel:
      changes in application times and success rates in three successive phases.
AB  - INTRODUCTION: Haemorrhage from the injured extremity is a significant cause of
      preventable death in military settings. This study evaluated the effect of
      training on the efficacy of the combat application tourniquet (CAT) and to define
      standards for military personnel. METHOD: Participants from a training tank
      battalion were randomised. Data collected included age, body mass index, mean
      arterial pressure, hand dominance, femoral artery diameter and skin thickness.
      The study involved tourniquet application times (AT) and application success
      rates in basic, after-training and eyes-closed phases. Doppler ultrasound was
      used to identify the presence or absence of popliteal, radial and ulnar artery
      pulses. RESULTS: A total of 102 trainees participated. In the after-training
      phase, the left and right upper extremity ATs were 35 +/- 13.1 s, and 34.8 +/-
      13.5 s and the right and left lower extremity ATs were 20.6 +/- 6.0 s and 20.5 +/
      5.5 s, respectively. The overall tourniquet success rates in three successive
      study phases were 69.6%, 82.4% and 91.2%, respectively. A negative significant
      relationship was found between extremity circumference and tourniquet success.
      DISCUSSION: The results show that the efficacy of CAT application increases with
      training. Further studies are required to investigate the reasons underlying
      application failures. This single group prospective randomised study involves
      level of evidence 4.

PMID- 25388481
TI  - Improving attendance at post-emergency department follow-up via automated text
      message appointment reminders: a randomized controlled trial.
AB  - OBJECTIVES: Patients discharged from the emergency department (ED) are often
      referred for primary care, specialty, or other disease-specific follow-up
      appointments. Attendance at these scheduled follow-up appointments has been found
      to improve patient outcomes, decrease ED bounce-backs, and reduce malpractice
      risk. Reasons for missing follow-up visits are complex, but the most commonly
      reason cited by patients is simply forgetting. In this study the authors
      evaluated the ability of an automated text message reminder system to increase
      attendance at post-ED discharge follow-up appointments in a predominantly
      Hispanic safety-net population. METHODS: This was a randomized controlled trial
      of ED patients with outpatient follow-up visits scheduled at the time of ED
      discharge. A total of 374 English- and Spanish-speaking patients with text
      capable mobile phones were enrolled. Patients in the intervention arm received
      automated, personalized text message appointment reminders including date, time,
      and clinic location at 7, 3, and 1 day before scheduled visits. A t-test of
      proportions was used to compare outcomes between intervention and control groups.
      Both an intention-to-treat (ITT) and a per-protocol analysis of the data were
      performed. The ITT more accurately reflects real-world conditions where errors
      such as number entry errors are bound to occur. The per-protocol analysis adds
      value by isolating the effect of the intervention by comparing patients who
      actually received it compared with those who did not. RESULTS: In the per
      protocol analysis of the primary outcome, the overall appointment adherence rate
      was 72.6% in the intervention group compared with 62.1% in the control group
      (difference between groups = 10.5%, 95% confidence interval [CI] = 0.3% to 20.8%;
      p = 0.045; number needed to treat = 9.5). In the ITT analysis, the overall
      appointment attendance rate 70.2% in the intervention group compared with 62.1%
      in the control group (difference between groups = 8.2%; 95% CI = -1.6% to 17.7%;
      p = 0.100). In a secondary largely exploratory analysis, the intervention was
      found to have the most benefit in patients with the lowest baseline follow-up
      rate (English speakers with specialty care appointments). CONCLUSIONS: Automated
      text message appointment reminders resulted in improvement in attendance at
      scheduled post-ED discharge outpatient follow-up visits and represent a low-cost
      and highly scalable solution to increase attendance at post-ED follow-up
      appointments, which should be further explored in larger sample sizes and diverse
      patient populations.

PMID- 25388482
TI  - Prevalence and factors associated with metabolic syndrome in elderly users of the
      Unified Health System.
AB  - OBJECTIVE: To evaluate the prevalence and factors associated with metabolic
      syndrome in the elderly. METHODS: Cross-sectional study, with 133 individuals
      randomly selected in the Unified Health System in Goiania, Goias. The following
      variables were researched: anthropometric (BMI, waist circumference, fat
      percentage by Dual X-ray absorptiometry), sociodemographic (gender, age, color,
      income, marital status and years of schooling), lifestyle (physical activity,
      smoking and risk alcohol consumption) and food intake (risk and protective
      foods). The metabolic syndrome was assessed according to harmonized criteria
      proposed by the World Health Organization (WHO). The combinations were tested by
      Poisson regression for confounding factors. RESULTS: The prevalence of metabolic
      syndrome was 58.65% (95%CI 49.8 - 67.1), with 60.5% (95%CI 49.01 - 71.18) for
      females and 55.7% (95%CI 41.33 - 69.53) for males. Hypertension was the most
      prevalent component of the syndrome in both men, with 80.8% (95%CI 64.5 - 90.4),
      and women, with 85.2% (95%CI 75.5 - 92.1). After the multivariate analysis, only
      the excess of weight measured by body mass index (prevalence ratio = 1.66; p <
      0.01) remained associated with the metabolic syndrome. CONCLUSIONS: The
      prevalence of metabolic syndrome in this sample was high, indicating the need for
      systematic actions by health workers in the control of risk factors through
      prevention strategies and comprehensive care to the elderly.

PMID- 25388483
TI  - Polypharmacy, chronic diseases and nutritional markers in community-dwelling
      older.
AB  - Polypharmacy is a common practice among the elderly, but few studies have
      evaluated its association with nutritional markers. The aim of this study was to
      estimate the prevalence of polypharmacy and its association with nutritional
      markers, chronic diseases, sociodemographic and health variables. This research
      is part of the Study Elderly/Goiania, which evaluated 418 elderly community in a
      cross-sectional design. Polypharmacy was defined as the use of five or more
      concomitant medications. The following nutritional markers were investigated:
      BMI, waist circumference, percentage body fat, weight gain and loss, use of diet,
      daily consumption of fruits, vegetables, skimmed and whole milk. Multivariate
      analysis was performed using hierarchical Poisson regression, with significance
      level set at 5%. The prevalence of polypharmacy was 28% (95%CI 23.1 - 32.5), with
      a significant association with feminine gender, age range 75 - 79 years,
      eutrophic nutritional status and obesity, use of diet, poor self-rated health and
      presence of two, three or more chronic diseases. The high prevalence of
      polypharmacy and its association with nutritional markers and chronic diseases
      call the attention for the need of nutritional surveillance and monitoring in the
      elderly. 

PMID- 25388484
TI  - Factors associated with work ability in the elderly: systematic review.
AB  - OBJECTIVE: To synthesize the evidence on factors associated with the maintenance
      of work ability during the aging process. METHODS: SciELO, LILACS and PubMed
      databases were consulted, in order to find out studies in Portuguese, English and
      Spanish published from 2000 to 2013. Descriptors which encompassed terms related
      to work ability, aging and elderly were used. Quantitative observational studies
      were included to investigate the work ability and the effect of aging. Studies
      aiming at analyzing the clinical course of illnesses related to aging and/or
      papers and publications in the form of editorials, interviews, projects, clinical
      notes and preliminary or conceptual data were excluded. RESULTS: A total of 924
      articles were obtained, but 27 were included in the analyses. Later on, 2
      intervention and 8 repeated studies were excluded. Variables that showed negative
      correlations with work ability were the following: age, smoking, service time and
      physical demands in occupational activities. Satisfaction with life, sufficient
      income, physical activity, volunteerism and mental workload were considered
      positive associations that protect the elderly from functional loss. CONCLUSION:
      This study was reported as a protective mechanism against depression, disability
      and fragility, maintaining the well-being, good cognitive function and autonomy
      in daily activities. Increased investments in the health care of this population
      are needed regarding musculoskeletal and cardiorespiratory capacity. Physical
      activity must be encouraged by policies to foster health promotion.

PMID- 25388485
TI  - Reasons behind the participation in biomedical research: a brief review.
AB  - INTRODUCTION: Clinical research is essential for the advancement of Medicine,
      especially regarding the development of new drugs. Understanding the reasons
      behind patients' decision of participating in these studies is critical for the
      recruitment and retention in the research. OBJECTIVES: To examine the decision
      making of participants in biomedical research, taking into account different
      settings and environments where clinical research is performed. METHODS: A
      critical review of the literature was performed through several databases using
      the keywords: "motivation", "decision", "reason", "biomedical research",
      "clinical research", "recruitment", "enrollment", "participation", "benefits",
      "altruism", "decline", "vulnerability" and "ethics", between August and November
      2013, in English and in Portuguese. RESULTS: The review pointed out that the
      reasons can be different according to some characteristics such as the disease
      being treated, study phase, prognoses and socioeconomic and cultural environment.
      Access to better health care, personal benefits, financial rewards and altruism
      are mentioned depending on the circumstances. CONCLUSION: Finding out more about
      individuals' reasons for taking part in the research will allow clinical
      investigators to design studies of greater benefit for the community and will
      probably help to remove undesirable barriers imposed to participation. Improving
      the information to health care professionals and patients on the benefits and
      risks of clinical trials is certainly a good start.

PMID- 25388486
TI  - Validity and reproducibility of a food frequency questionnaire for adults of Sao
      Paulo, Brazil.
AB  - OBJECTIVES: To assess the validity and reproducibility of a food frequency
      questionnaire developed for estimating the food consumption of adults in Sao
      Paulo, Brazil, based population study. METHODS: A sample of individuals aged
      above 20 years, of both genders, living in Sao Paulo, was used for the validation
      study (n = 77) and reproducibility study (n = 74) of the food frequency
      questionnaire. To verify the validity and reproducibility of energy and 19
      nutrients were applied two food frequency questionnaires (60 items) and three 24
      hour dietary recalls (24HR - reference method). The validity was verified by
      Spearman correlation coefficient (crude and de-attenuated) and weighted Kappa,
      and reproducibility by intraclass correlation coefficients and weighted kappa.
      RESULTS: In analyzes of validity de-attenuated correlation coefficients ranged
      from 0.21 (carbohydrate) to 0.74 (energy), and weighted kappa exceeded 0.40 for
      30% of the nutrients. Polyunsaturated fat and folate did not show significant
      correlation and weighted kappa. In reproducibility correlation coefficients
      ranged from 0.36 (polyunsaturated fat) to 0.69 (calcium), and weighted kappa
      exceeded 0.40 for 80% of the nutrients. CONCLUSION: The food frequency
      questionnaire analyzed has good validity and reproducibility for estimating the
      food consumption of adults in Sao Paulo compared to the reference method, so it
      is an appropriate instrument to be used in epidemiological studies on similar
      populations. Estimates of polyunsaturated fat and folate should be interpreted
      with caution.

PMID- 25388487
TI  - Overweight among children under five years of age in municipalities of the
      semiarid region.
AB  - OBJECTIVE: To measure the prevalence and to identify factors associated with
      overweight among children under five years old living in two municipalities in
      the semiarid region of Piaui, Brazil. METHODS: Previously trained interviewers
      visited all of the households in these municipalities and applied standard
      questionnaires to the mothers of the children. The questionnaires sought
      information on: the demographic characteristics of the mother and children, the
      family's socioeconomic status, care received during pregnancy and at childbirth,
      breastfeeding and dietary patterns. Overweight (>+ 1 standard deviation from the
      median to the reference population) was calculated transforming body mass index
      into Z scores, according to the standard by the World Health Organization (WHO).
      The statistical analysis was performed using Poisson regression with robust
      adjustment of variance. RESULTS: The prevalence of overweight among the 1,640
      children evaluated was of 30.2% (95%CI 27.9 - 32.4). This prevalence varied from
      13.2% among children born weighing less than 2,500 g to 43.4% among those aged 12
      to 23 months. Adjusted analysis showed that the prevalence ratios (PR) for
      overweight in children aged 48 to 59 months was 1.42 (1.07 - 1.86) for overweight
      compared to those aged between 0 and 11 months, whereas children pertaining to
      the highest quartile income showed PR = 1.44 (1.17 - 1.76) when compared to the
      lowest quartile. Finally, children born with weight >= 3500 g, the PR for
      overweight was 2.32 (1.33 - 4.05) in relation to those born with low weight (<
      2500 g). CONCLUSION: Even in the semiarid region, the prevalence of overweight is
      high, and the need for early intervention to change this situation seems to be
      evident.

PMID- 25388488
TI  - Positive impact of child feeding training program for primary care health
      professionals: a cluster randomized field trial.
AB  - OBJECTIVE: To assess the impact of a child feeding training program for primary
      care health professionals about breastfeeding and complementary feeding
      practices. METHODS: Cluster-randomized field trial conducted in the city of Porto
      Alegre, (RS), Brazil. Twenty primary health care centers (HCC) were randomized
      into intervention (n = 9) and control (n = 11) groups. The health professionals
      (n = 200) at the intervention group centers received training about healthy
      feeding practices. Pregnant women were enrolled at the study. Up to six months of
      child's age, home visits were made to obtain variables related to breastfeeding
      and introduction of foods. RESULTS: 619 children were evaluated: 318 from the
      intervention group and 301 from the control group. Exclusive breastfeeding
      prevalence in the first (72.3 versus 59.4%; RR = 1.21; 95%CI 1.08 - 1.38), second
      (62.6 versus 48.2%; RR = 1.29; 95%CI 1.10 - 1.53), and third months of life
      (44.0% versus 34.6%; RR = 1.27; 95%CI 1.04 - 1.56) was higher in the intervention
      group compared to the control group. The prevalence of children who consumed meat
      four or five times per week was higher in the intervention group than in the
      control group (36.8 versus 22.6%; RR = 1.62; 95%CI 1.32 - 2.03). The prevalence
      of children who had consumed soft drinks (34.9 versus 52.5%; RR = 0.66; 95%CI
      0.54 - 0.80), chocolate (24.5 versus 36.7% RR = 0.66 95%CI 0.53 - 0.83), petit
      suisse (68.9 versus 79.7; 95%CI 0.75 - 0.98) and coffee (10.4 versus 20.1%; RR =
      0.51; 95%CI 0.31 - 0.85) in their six first months of life was lower in the
      intervention group. CONCLUSION: The training of health professionals had a
      positive impact on infant feeding practices, contributing to the promotion of
      child health.

PMID- 25388489
TI  - Barriers to control syphilis and HIV vertical transmission in the health care
      system in the city of Sao Paulo.
AB  - OBJECTIVE: The objective of this study was to identify possible barriers to
      control vertical transmission of syphilis and HIV through the analysis of the
      orientation process of pregnant women from prenatal care to the obstetric center
      at an university hospital in Sao Paulo (Reference) and their return (with their
      exposed babies) for follow-up after hospital discharge (counter-reference).
      METHODS: It is a retrospective cross-sectional study including interviews with
      healthcare personnel. Pregnant women with syphilis and/or HIV-infection admitted
      for labor or miscarriage were identified from August 2006 to August 2007. Routine
      care for mothers and babies were analyzed. RESULTS: 56 pregnant women were
      identified: 43 were HIV-infected, 11 had syphilis and two were coinfected
      (syphilis/HIV); 22 health care professionals were interviewed. Prenatal care was
      identified in 91.1% of these women: 7/11 (63.6%) with syphilis; 44/45 (97.8%) HIV
      infected or coinfected. The reference for delivery was satisfactory for 57.7% of
      the syphilis-infected women and 97.7% of the HIV-infected ones. The counter
      reference was satisfactory for all babies and mothers at hospital discharge,
      besides the non-adherence to this recommendation. Interviews with health care
      professionals showed there are better routines for assisting and following-up
      pregnant women, puerperal women and HIV-infected or exposed babies than for those
      infected with syphilis. The epidemiological report and surveillance system are
      also better for HIV-infected patients. CONCLUSION: The difficulties in the
      reference and counter-reference system of these women and their babies are
      evident barriers to control the vertical transmission of these infectious
      diseases.

PMID- 25388490
TI  - Neural complications and physical disabilities in leprosy in a capital of
      northeastern Brazil with high endemicity.
AB  - INTRODUCTION: Leprosy is an infectious disease whose etiologic agent is
      Mycobacterium leprae, manifested by dermatological and neurological signs and
      symptoms. OBJECTIVE: To investigate neural changes and the degree of physical
      disability in the eyes, hands and feet before and after treatment, as well as
      sociodemographic and clinical profile of patients affected by leprosy. METHOD: A
      longitudinal epidemiological study comprising 155 patients with leprosy, from a
      spontaneous demand, diagnosed between March 2010 and February 2011, and treated
      with multidrug therapy (MDT) between March 2010 and July 2012 in a program for
      leprosy eradication in Sao Luis (MA), Brazil. RESULTS: Before treatment, 46.5% of
      patients were considered as borderline, 51.6% had some alteration in the eyes and
      52.3% in the feet, and the radial nerve (18.7%) was the most affected. There was
      a statistically significant difference between the changes in the radial nerve at
      the beginning of and after treatment. CONCLUSIONS: The analysis points to late
      diagnosis, as some patients have had abnormal neural and physical disabilities
      before treatment.

PMID- 25388491
TI  - Epidemiological aspects of visceral leishmaniasis (kala-azar) in Ceara in the
      period 2007 to 2011.
AB  - INTRODUCTION: Visceral leishmaniasis (VL; kala-azar) is a serious zoonosis that
      can be lethal, especially in untreated patients. Due to the fact that the State
      of Ceara is still an important area of transmission of VL, and based on the
      constant reports of the urbanization process of the disease in the country, it
      was necessary to monitor the occurrence of cases of leishmaniasis through
      epidemiological surveillance. OBJECTIVES: To describe the epidemiology of
      leishmaniasis cases in Ceara, Brazil. METHODS: We conducted an epidemiological
      survey of secondary data provided by SINAN/MS from January 2007 to December 2011.
      RESULTS: VL is an endemic disease in the State of Ceara, with cases notified in
      approximately 88% of the municipalities, with an average of 596.8 +/- 29.6 cases,
      an incidence of 6.1 cases/100,000 inhabitants and prevalence of 7.1 cases/100,000
      inhabitants. The Metropolitan Region of Fortaleza is the microregion with the
      largest number of cases reported in state (51.9% of cases), with the capital,
      Fortaleza, being the municipality with the highest number of cases in the
      country. Traditionally, the main age group affected by the disease are children;
      however, a reversal has been observed in the profile from 2008, when the
      population of adult patients exceeded the pediatric population. CONCLUSION: Ceara
      is still an endemic area for VL, and the city of Fortaleza reported the highest
      number of cases in the country. In the State, a change in the profile of patients
      with the disease has been observed, now affecting primarily adults.

PMID- 25388492
TI  - Physical activity, adiposity and hypertension among patients of public healthcare
      system.
AB  - INTRODUCTION: Hypertension is a chronic disease that requires special attention
      in identifying comorbidities or risk factors including inactivity and obesity.
      Considering that a large proportion of the Brazilian population is hypertensive,
      obese, and sedentary, the relationship among these variables in the context of
      the public health system is unclear. OBJECTIVE: To assess the association among
      physical activity, markers of adiposity, and hypertension in adult users of the
      public healthcare system in the city of Bauru, Sao Paulo, Brazil. METHODS: The
      study was conducted in five Basic Health Units in Bauru, Sao Paulo, and consisted
      of 963 patients. Data were collected from habitual physical activity and previous
      (childhood and adolescence), education, purchasing power and anthropometric
      markers of overall and abdominal obesity. RESULTS: The incidence of hypertension
      was 76.8%. Significant associations were found among sedentarism, presence of
      total and abdominal obesity, with the higher incidence of hypertension. It was
      also observed that the magnitude of association between hypertension and
      adiposity increased with decreased involvement in physical activity. CONCLUSION:
      Further investigations are needed to analyze the occurrence of overweight and
      obesity in people suffering from chronic diseases in order to prevent future
      complications.

PMID- 25388493
TI  - Perceived neighborhood environment and physical activity among high school
      students from Curitiba, Brazil.
AB  - OBJECTIVE: To analyze the association between perceived neighborhood environment
      and physical activity (PA) in high school students from Curitiba (PR), Brazil.
      METHODS: A sample of 1,611 high school students from public schools was surveyed.
      The PA was assessed through questions, engaged for at least 20 minutes or 60
      minutes. Perceptions on neighborhood environment were assessed through ten
      questions about neighborhood characteristics. Gender, age and number of cars in
      the household were self-reported and used as confounding variables. Absolute and
      relative frequencies were used in the sample, and associations were tested
      through adjusted logistic regressions for the confounding variables and
      stratified by gender (p < 0.05). RESULTS: The adjusted analyses showed that the
      variables "interesting things" among girls (OR = 1.77; 95%CI 1.05 - 2.96) and
      "there are places I like" (OR = 2.18; 95%CI 1.33 - 3.58) and "I see people my
      age", among boys, were associated with PA of at least 20 minutes/day once a week.
      Additionally, among boys, "I see people my age" was associated with 60-minute (OR
      = 1.68; 95%CI 1.15 - 2.45). Perceiving the neighborhood environment as "very
      good" was associated with higher chances of taking up PA among girls (OR = 1.92;
      95%CI 1.15 - 3.22) and boys (OR = 3.13; 95%CI 1.97 - 4.97). CONCLUSION: A
      positive perception of the environment was associated to PA practice among boys
      and girls in this sample. The results suggest that some environmental
      characteristics which make neighborhoods more attractive could be related to PA
      among adolescents.

PMID- 25388494
TI  - Morbidity in users of family health teams in the northeast of Minas Gerais based
      on the International Classification of Primary Care.
AB  - This study aimed to characterize the profile of morbidity among users of family
      health teams in the northeastern macroregion of Minas Gerais, Brazil. This is a
      cross-sectional population-based study, developed with the teams of the Family
      Health Strategy (FHS). It was conducted by data collection, using semi-structured
      questionnaires with specific instruments adjusted for three categories of
      professional teams of the FHS: physicians, nurses and community health agents
      (CHA). We used the International Classification of Primary Care, second edition
      (ICPC-2) to encode morbidity. Information was collected from 17,988 people, and
      10,855 (60.3%) were females; 1,662 (9.2%) questionnaires were related to care by
      the physician; 2,530 (14.1%) were related to care by nurses and 13,796 (76.7%)
      corresponded to visits by and meetings with the CHA. The main health problems
      were: circulatory diseases (especially hypertension), musculoskeletal problems
      (especially back pain) and diseases of the digestive tract (especially intestinal
      parasites), which accounted for more than 40% of the medical consultations.
      Nonspecific complaints and visits related to women's health were the most
      prevalent in the care by nurses. In meetings with CHA, complaints about
      respiratory, musculoskeletal and cardiovascular diseases were the most pointed.
      The morbidity profile observed does not differ substantially from the results of
      other studies. Small differences can be attributed to regional particularities. 

PMID- 25388495
TI  - Hospitalization due to conditions sensitive to primary care and expansion of the
      Family Health Program in Brazil: an ecological study.
AB  - OBJECTIVE: To evaluate the relationship between hospitalization due to conditions
      that are sensitive to primary care and the population coverage by the Family
      Health Strategy (ESF) Units of the Brazilian Federation Units in the last decade.
      METHODS: This is an ecological study that investigated preventable
      hospitalizations and coverage of primary health care in Brazil in the historic
      series from 1998 to 2006. Statistical analysis was performed using the Pearson
      correlation test and simple linear regression. RESULTS: In the studied period, we
      found an association between population coverage and reduced ESF admissions for
      primary care sensitive conditions in Brazil (beta = -28.78, p <= 0.01), which
      occurred in 38.4% of the Federation Units. CONCLUSION: There was a positive
      relationship between the expansion of ESF coverage and a decline in
      hospitalizations for ACSC in the country. The findings of this study help to
      evaluate the ESF and primary care in Brazil.

PMID- 25388496
TI  - Variables associated with the performance of Centers for Dental Specialties in
      Brazil.
AB  - The aim of this study was to evaluate the performance of the Centers for Dental
      Specialties (CDS) in the country and associations with sociodemographic
      indicators of the municipalities, structural variables of services and primary
      health care organization in the years 2004-2009. The study used secondary data
      from procedures performed in the CDS to the specialties of periodontics,
      endodontics, surgery and primary care. Bivariate analysis by chi2 test was used
      to test the association between the dependent variable (performance of the CDS)
      with the independents. Then, Poisson regression analysis was performed. With
      regard to the overall achievement of targets, it was observed that the majority
      of CDS (69.25%) performance was considered poor/regular. The independent factors
      associated with poor/regular performance of CDS were: municipalities belonging to
      the Northeast, South and Southeast regions, with lower Human Development Index
      (HDI), lower population density, and reduced time to deployment. HDI and
      population density are important for the performance of the CDS in Brazil.
      Similarly, the peculiarities related to less populated areas as well as regional
      location and time of service implementation CDS should be taken into account in
      the planning of these services. 

PMID- 25388497
TI  - Smoking in adults in the municipality of Rio Branco, Acre, Brazil: a population
      based study.
AB  - OBJECTIVE: To analyze the associations between smoking and socioeconomic status,
      and to analyze the profile of smokers in the city of Rio Branco, Acre. METHODS: A
      population-based cross-sectional study conducted with 1,512 adults living in
      urban and rural areas. Information about demographic aspects, socioeconomic
      status and smoking habits were collected through home interviews. Crude and
      adjusted prevalence ratios with their respective 95% confidence intervals were
      calculated by Poisson regression. RESULTS: The overall prevalence of smoking was
      of 19.9%. Males had a higher prevalence (22.7%) in contrast to females (17.6%).
      By age, a higher prevalence was observed at 50 - 59 years in males (30.9%) and at
      40 - 49 years in females (23.8%). A linear trend was observed between the higher
      prevalence of smoking and the lower amount of years of education and income (p <
      0.05). The profile of smokers indicated that the majority, in both genders, began
      smoking at age 15, smoked between 1 and 10 cigarettes per day, lit the first
      cigarette of the day 60 minutes after waking up and had tried to quit smoking at
      least twice. CONCLUSION: The high prevalence of smoking is a relevant public
      health problem in Rio Branco. Community actions must be implemented for the
      prevention and control of tobacco use.

PMID- 25388498
TI  - Survival and prognostic factors in patients with non-small cell lung cancer
      treated in private health care.
AB  - INTRODUCTION: Outcomes data on Non-Small Cell Lung Cancer (NSCLC) are scarce with
      regard to the private health care in Brazil. The aim of this study was to
      describe the characteristics, treatments performed, and the survival of patients
      with NSCLC in a Brazilian private oncologic institution. METHODS: Medical charts
      from patients treated between 1998 and 2010 were reviewed, and data were
      transferred to a clinical research form. Long-term follow-up and survival
      estimates were enabled through active surveillance. RESULTS: Five hundred sixty
      six patients were included, and median age was 65 years. Most patients were
      diagnosed in advanced stages (79.6% III/IV). The overall survival was 19.0 months
      (95%CI 16.2 - 21.8). The median survival was 99.7, 32.5, 20.2, and 13.3 months
      for stages I, II, III, and IV, respectively (p < 0.0001). Among patients
      receiving palliative chemotherapy, the median survival was 12.2 months (95%CI
      10.0 - 14.4). CONCLUSIONS: The outcomes described are favorably similar to the
      current literature from developed countries. Besides the better access to health
      care in the private insurance scenario, most patients are still diagnosed in late
      stages.

PMID- 25388499
TI  - The Porto Alegre Early Life Nutrition and Health Study.
AB  - Early childhood caries is a persistent worldwide problem. The etiologic
      contribution of feeding practices has been less frequently investigated in
      prospective studies of young children. The Porto Alegre Early Life Nutrition and
      Health Study has followed a birth cohort of 715 mother-child pairs, recruited
      from municipal health centers, originally involved in a cluster-randomized
      controlled trial of healthcare worker training. The birth cohort links
      prospectively collected socio-demographic, infant feeding, and general and oral
      health information. To date, oral health data, including caries status and oral
      health-related quality of life, have been collected for 458 children at the age
      of 2-3 years. Studies are underway to investigate possible determinants and
      consequences of oral health among these children. 

PMID- 25388500
TI  - Sea snake harvest in the gulf of Thailand.
AB  - Conservation of sea snakes is virtually nonexistent in Asia, and its role in
      human-snake interactions in terms of catch, trade, and snakebites as an
      occupational hazard is mostly unexplored. We collected data on sea snake landings
      from the Gulf of Thailand, a hotspot for sea snake harvest by squid fishers
      operating out of the ports of Song Doc and Khanh Hoi, Ca Mau Province, Vietnam.
      The data were collected during documentation of the steps of the trading process
      and through interviewers with participants in the trade. Squid vessels return to
      ports once per lunar synodic cycle and fishers sell snakes to merchants who sort,
      package, and ship the snakes to various destinations in Vietnam and China for
      human consumption and as a source of traditional remedies. Annually, 82 t,
      roughly equal to 225,500 individuals, of live sea snakes are brought to ports. To
      our knowledge, this rate of harvest constitutes one of the largest venomous snake
      and marine reptile harvest activities in the world today. Lapemis curtus and
      Hydrophis cyanocinctus constituted about 85% of the snake biomass, and
      Acalyptophis peronii, Aipysurus eydouxii, Hydrophis atriceps, H. belcheri, H.
      lamberti, and H. ornatus made up the remainder. Our results establish a
      quantitative baseline for characteristics of catch, trade, and uses of sea
      snakes. Other key observations include the timing of the trade to the lunar
      cycle, a decline of sea snakes harvested over the study period (approximately 30%
      decline in mass over 4 years), and the treatment of sea snake bites with
      rhinoceros horn. Emerging markets in Southeast Asia drive the harvest of venomous
      sea snakes in the Gulf of Thailand and sea snake bites present a potentially
      lethal occupational hazard. We call for implementation of monitoring programs to
      further address the conservation implications of this large-scale marine reptile
      exploitation.

PMID- 25388502
TI  - Effect of the electropositive elements A = Sc, La, and Ce on the microscopic
      dynamics of AV2Al20.
AB  - We report on the inelastic response of AV2Al20 (with A = Sc, La and Ce) probed by
      high-resolution inelastic neutron scattering experiments. Intense signals
      associated with the dynamics of Sc, La and Ce are identified in the low-energy
      range at 6-14 meV in ScV2Al20 and at 8-16 meV in LaV2Al20 and CeV2Al20. Their
      response to temperature changes between 2 and 300 K reveals a very weak softening
      of the modes upon heating in LaV2Al20 and CeV2Al20 and a distinguished blue shift
      by about 2 meV in ScV2Al20. By means of density functional theory (DFT) and
      lattice dynamics calculations (LDC) we show that the unusual anharmonicity of the
      Sc-dominated modes is due to the local potential of Sc featured by a strong
      quartic term. The vibrational dynamics of ScV2Al20 as well as of LaV2Al20 and
      CeV2Al20 is reproduced by a set of eigenmodes. To screen the validity of the DFT
      and LDC results they are confronted with data from X-ray diffraction
      measurements. The effect of the strong phonon renormalization in ScV2Al20 on
      thermodynamic observables is computed on grounds of the LDC derived inelastic
      response. To set the data in a general context of AV2Al20 compounds and their
      physical properties we report in addition computer and experimental results of
      the binary V2Al20 compound. 

PMID- 25388503
TI  - Target control of complex networks.
AB  - Controlling large natural and technological networks is an outstanding challenge.
      It is typically neither feasible nor necessary to control the entire network,
      prompting us to explore target control: the efficient control of a preselected
      subset of nodes. We show that the structural controllability approach used for
      full control overestimates the minimum number of driver nodes needed for target
      control. Here we develop an alternate 'k-walk' theory for directed tree networks,
      and we rigorously prove that one node can control a set of target nodes if the
      path length to each target node is unique. For more general cases, we develop a
      greedy algorithm to approximate the minimum set of driver nodes sufficient for
      target control. We find that degree heterogeneous networks are target
      controllable with higher efficiency than homogeneous networks and that the
      structure of many real-world networks are suitable for efficient target control. 

PMID- 25388504
TI  - Rayleigh scattering in coupled microcavities: theory.
AB  - In this paper we theoretically study how structural disorder in coupled
      semiconductor heterostructures influences single-particle scattering events that
      would otherwise be forbidden by symmetry. We extend the model of Savona (2007 J.
      Phys.: Condens. Matter 19 295208) to describe Rayleigh scattering in coupled
      planar microcavity structures, and find that effective filter theories can be
      ruled out.

PMID- 25388505
TI  - The Specificity of the Interpersonal-Psychological Theory of Suicidal Behavior
      for Identifying Suicidal Ideation in an Online Sample.
AB  - The interpersonal-psychological theory of suicidal behavior suggests that the
      combination of perceived burdensomeness and thwarted belongingness predicts
      suicidal ideation. However, the specificity of this prediction to suicidal
      ideation has not been tested. This study examined whether these constructs were
      consistently associated with different characteristics of suicidal ideation, and
      whether they were associated with mental health problems more broadly, in an
      online sample of 1,352 Australian adults. Findings indicated that the interaction
      between perceived burdensomeness and thwarted belongingness was associated only
      with suicidal ideation and consistent across multiple characteristics of
      ideation. The study broadly supported the specificity of the IPTS. 

PMID- 25388506
TI  - Protective effect of ebselen on experimental testicular torsion and detorsion
      injury.
AB  - Ebselen is used as a drug in clinical trials against stroke, reperfusion injury
      with anti-atherosclerotic and renoprotective effects. The aim of this study is to
      investigate the protective effect of ebselen, on torsion/detorsion (T/D)-induced
      biochemical and histopathological changes in experimental testicular
      ischaemia/reperfusion injury. A total of 28 male Wistar Albino rats were divided
      into four groups: group 1(sham-operated group, n = 7), group 2(ebselen group, n =
      7), group 3(torsion/detorsion + saline, n = 7) and group 4(T/D + 10 mg kg(-1)
      ebselen group, n = 7). The tissue homogenate samples were used for immediate
      nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase, catalase and
      glutathione measurement. Testes in all groups were evaluated for the biochemical
      assay and histopathological examinations. To evaluate spermatogenesis, Johnsen
      scoring system was used. Testicular tissue MDA and NO levels in group 3 were
      significantly higher than in group 1 and 4. In histological evaluation of the
      testicular tissues, ebselen administration improved tubular histology
      significantly compared with T/D group. Significant increase in histological score
      was observed in the testis of group 3 compared with group 1 and 2. Histological
      score in group 4 significantly decreased compared with group 3. Johnson score was
      significantly lower in T/D group compared with all other three groups, ebselen
      administration increased the score significantly compared with T/D group. Ebselen
      reduced oxidative biochemical and histopathological damage in our testicular T/D
      rat model. 

PMID- 25388507
TI  - How to do an endofascial axillary lymphadenectomy.

PMID- 25388508
TI  - Exposure to 2,5-hexanedione is accompanied by ovarian and uterine oxidative
      stress and disruption of endocrine balance in rats.
AB  - 2,5-Hexanedione (2,5-HD) is an aliphatic diketone identified as the main
      neurotoxic metabolite of the industrial chemicals n-hexane and methyl-n-butyl
      ketone. Considering the dearth of information on the female reproductive toxicity
      effects of 2,5-HD in the literature, we assessed the potential oxidative stress
      mechanisms of 2,5-HD in the ovary and uterus of Wistar rats. A total of 32 female
      rats were randomly allotted to four groups, in which rats were exposed to 2,5-HD
      at doses of 0% (control), 0.25%, 0.5% and 1.0% respectively in their drinking
      water for 21 days. The results showed that 2,5-HD significantly increased ovarian
      and uterine malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels (p < 0.05).
      Additionally, while significant decreases in ovarian catalase, superoxide
      dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase
      (GST) activities occurred in all the 2,5-HD-treated groups, uterine catalase,
      GST, and GPx activities increased. Further, 2,5-HD increased follicle stimulating
      hormone, but decreased estrogen levels in all the 2,5-HD-treated groups, while
      prolactin increased in the 0.5, and 1.0% 2,5-HD-treated rats compared with the
      control (p < 0.05). Thus, these data imply that 2,5-HD exposure disrupts hormonal
      homeostasis and induces oxidative stress in the ovary and uterus of rats. These
      findings may therefore have toxicological implications in women occupationally
      exposed to n-hexane and methyl-n-butyl ketone. 

PMID- 25388509
TI  - Transient effect of single dose exposure of Nigerian Bonny-light crude oil on
      testicular steroidogenesis in Wistar rats is accompanied by oxidative stress.
AB  - The folkloric use of Nigerian Bonny-light crude oil (BLCO) in Niger Delta area of
      Nigeria is a common practice. There is increasing experimental evidence
      portending the adverse effects of BLCO an environmental toxicant on testicular
      function. We investigated the effects of single dose of BLCO (800 mg/kg body
      weight) on the activities of steroidogenic and antioxidant enzymes such as serum
      follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, 3
      beta-hydroxy-steroid dehydrogenase (3 beta-HSD), 17 beta-hydroxy-steroid
      dehydrogenase (17 beta-HSD), superoxide dismutase (SOD), glutathione-S
      transferase (GST) and glutathione peroxidase (GSH-Px), levels of lipid
      peroxidation (LPO), glutathione reduced (GSH) and steroidogenic acute regulatory
      (StAR) protein, in testes of rats. There was a sequential reduction in the
      concentration of steroid hormones and activities of steroidogenic enzymes with a
      concomitant decrease in levels of StAR protein, followed by a parallel increase
      in antioxidant enzyme activities and levels of LPO. These findings revealed
      inhibitory effects of BLCO on testicular steroidogenesis and the possible role of
      oxidative stress in testicular dysfunction observed in this study. 

PMID- 25388510
TI  - Cutaneous mitochondrial respirometry: non-invasive monitoring of mitochondrial
      function.
AB  - The recently developed technique for measuring cutaneous mitochondrial oxygen
      tension (mitoPO2) by means of the Protoporphyrin IX-Triplet State Lifetime
      Technique (PpIX-TSLT) provides new opportunities for assessing mitochondrial
      function in vivo. The aims of this work were to study whether cutaneous
      mitochondrial measurements reflect mitochondrial status in other parts of the
      body and to demonstrate the feasibility of the technique for potential clinical
      use. The first part of this paper demonstrates a correlation between alterations
      in mitochondrial parameters in skin and other tissues during endotoxemia.
      Experiments were performed in rats in which mitochondrial dysfunction was induced
      by a lipopolysaccharide-induced sepsis (n = 5) and a time control group (n = 5).
      MitoPO2 and mitochondrial oxygen consumption (mitoVO2) were measured using PpIX
      TSLT in skin, liver and buccal mucosa of the mouth. Both skin and buccal mucosa
      show a significant mitoPO2-independent decrease (P < 0.05) in mitoVO2 after LPS
      infusion (a decrease of 37 and 39% respectively). In liver both mitoPO2 and
      mitoVO2 decreased significantly (33 and 27% respectively). The second part of
      this paper describes the clinical concept of monitoring cutaneous mitochondrial
      respiration in man. A first prototype of a clinical PpIX-TSLT monitor is
      described and its usability is demonstrated on human skin. We expect that
      clinical implementation of this device will greatly contribute to our
      understanding of mitochondrial oxygenation and oxygen metabolism in perioperative
      medicine and in critical illness. Our ultimate goal is to develop a clinical
      monitor for mitochondrial function and the current results are an important step
      forward.

PMID- 25388511
TI  - Reliability of the volatile agent consumption display in the Draeger PrimusTM
      anesthesia machine.
AB  - Knowledge of the consumed amount of volatile anesthetic (VA) expressed in liquid
      agent is necessary to enable agent sparing dosing measures and for billing
      purposes. The widespread Draeger PrimusTM anesthesia machine displays in its
      logbook the amount of consumed VA at the end of each anesthesia, but the
      reliability of this parameter is yet unknown. The objective was to evaluate the
      precision and reliability of the inbuilt VA consumption display in Draeger
      PrimusTM anesthesia machines as compared with the gold standard of weighing the
      vaporizer before and after anesthesia. In this prospective laboratory
      investigation we compared the VA consumption displayed by the Draeger PrimusTM
      anesthesia machine with measured vaporizer weight differences before and after 10
      sevoflurane and 10 desflurane anesthesias. We assessed the average difference and
      spread of values between the predicted (displayed) and measured (control) values
      for VA consumption. The displayed sevoflurane consumption overestimated the
      measured values by 4.3 +/- 5.4 ml (7.6%). The displayed desflurane consumption
      underestimated the measured values by -3.5 +/- 6.3 ml (6.2%). Nine from 10
      sevoflurane pairs of values and all desflurane pairs of values were within +/
      1.96 SD. The displayed VA consumption calculations for sevoflurane and desflurane
      in the Draeger PrimusTM are sufficiently reliable to estimate the
      pharmacoeconomic impact of VA delivery during inhalational anesthesia.

PMID- 25388512
TI  - Insecure attachment is associated with paranoia but not hallucinations in
      psychotic patients: the mediating role of negative self-esteem.
AB  - BACKGROUND: A growing body of research has investigated associations between
      insecure attachment styles and psychosis. However, despite good theoretical and
      epidemiological reasons for hypothesising that insecure attachment may be
      specifically implicated in paranoid delusions, few studies have considered the
      role it plays in specific symptoms. METHOD: We examined the relationship between
      attachment style, paranoid beliefs and hallucinatory experiences in a sample of
      176 people with a diagnosis of schizophrenia spectrum disorders and 113 healthy
      controls. We also investigated the possible role of negative self-esteem in
      mediating this association. RESULTS: Insecure attachment predicted paranoia but
      not hallucinations after co-morbidity between the symptoms was controlled for.
      Negative self-esteem partially mediated the association between attachment
      anxiety and clinical paranoia, and fully mediated the relationship between
      attachment avoidance and clinical paranoia. CONCLUSIONS: It may be fruitful to
      explore attachment representations in psychological treatments for paranoid
      patients. If future research confirms the importance of disrupted attachment as a
      risk factor for persecutory delusions, consideration might be given to how to
      protect vulnerable young people, for example those raised in children's homes.

PMID- 25388513
TI  - Suppression of homologous recombination sensitizes human tumor cells to IGF-1R
      inhibition.
AB  - Inhibition of type 1 IGF receptor (IGF-1R) sensitizes to DNA-damaging cancer
      treatments, and delays repair of DNA double strand breaks (DSBs) by non
      homologous end-joining and homologous recombination (HR). In a recent screen for
      mediators of resistance to IGF-1R inhibitor AZ12253801, we identified RAD51,
      required for the strand invasion step of HR. These findings prompted us to test
      the hypothesis that IGF-1R-inhibited cells accumulate DSBs formed at endogenous
      DNA lesions, and depend on residual HR for their repair. Indeed, initial
      experiments showed time-dependent accumulation of gammaH2AX foci in IGF-1R 
      inhibited or -depleted prostate cancer cells. We then tested effects of
      suppressing HR, and found that RAD51 depletion enhanced AZ12253801 sensitivity in
      PTEN wild-type prostate cancer cells but not in cells lacking functional PTEN.
      Similar sensitization was induced in prostate cancer cells by depletion of BRCA2,
      required for RAD51 loading onto DNA, and in BRCA2(-/-) colorectal cancer cells,
      compared with isogenic BRCA2(+/-) cells. We also assessed chemical HR inhibitors,
      finding that RAD51 inhibitor BO2 blocked RAD51 focus formation and sensitized to
      AZ12253801. Finally, we tested CDK1 inhibitor RO-3306, which impairs HR by
      inhibiting CDK1-mediated BRCA1 phosphorylation. R0-3306 suppressed RAD51 focus
      formation consistent with HR attenuation, and sensitized prostate cancer cells to
      IGF-1R inhibition, with 2.4-fold reduction in AZ12253801 GI50 and 13-fold
      reduction in GI80. These data suggest that responses to IGF-1R inhibition are
      enhanced by genetic and chemical approaches to suppress HR, defining a population
      of cancers (PTEN wild-type, BRCA mutant) that may be intrinsically sensitive to
      IGF-1R inhibitory drugs.

PMID- 25388516
TI  - Exciting new opportunities for communicating scientific information.

PMID- 25388514
TI  - Role of the aminotransferase domain in Bacillus subtilis GabR, a pyridoxal 5'
      phosphate-dependent transcriptional regulator.
AB  - MocR/GabR family proteins are widely distributed prokaryotic transcriptional
      regulators containing pyridoxal 5'-phosphate (PLP), a coenzyme form of vitamin
      B6. The Bacillus subtilis GabR, probably the most extensively studied MocR/GabR
      family protein, consists of an N-terminal DNA-binding domain and a PLP-binding C
      terminal domain that has a structure homologous to aminotransferases. GabR
      suppresses transcription of gabR and activates transcription of gabT and gabD,
      which encode gamma-aminobutyrate (GAlphaBetaAlpha) aminotransferase and succinate
      semialdehyde dehydrogenase, respectively, in the presence of PLP and GABA. In
      this study, we examined the mechanism underlying GabR-mediated gabTD
      transcription with spectroscopic, crystallographic and thermodynamic studies,
      focusing on the function of the aminotransferase domain. Spectroscopic studies
      revealed that GABA forms an external aldimine with the PLP in the
      aminotransferase domain. Isothermal calorimetry demonstrated that two GabR
      molecules bind to the 51-bp DNA fragment that contains the GabR-binding region.
      GABA minimally affected DeltaG(binding) upon binding of GabR to the DNA fragment
      but greatly affected the contributions of DeltaH and DeltaS to DeltaG(binding).
      GABA forms an external aldimine with PLP and causes a conformational change in
      the aminotransferase domain, and this change likely rearranges GabR binding to
      the promoter and thus activates gabTD transcription.

PMID- 25388518
TI  - Conservative care for ESRD in the United Kingdom: a national survey.
AB  - BACKGROUND AND OBJECTIVES: Conservative kidney management (CKM) has been
      developed in the United Kingdom (UK) as an alternative to dialysis for older
      patients with stage 5 CKD (CKD5) and multiple comorbidities. This national survey
      sought to describe the current scale and pattern of delivery of conservative care
      in UK renal units and identify their priorities for its future development.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A survey on practice patterns of
      CKM for patients age 75 and older with CKD5 was sent to clinical directors of all
      71 adult renal units in the UK in March 2013. RESULTS: Sixty-seven units (94%)
      responded. All but one unit reported providing CKM for some patients. Terminology
      varied, although "conservative management" was the most frequently used term
      (46%). Lack of an agreed-upon definition of when a patient is receiving CKM made
      it difficult to obtain meaningful data on the numbers of such patients. Fifty-two
      percent provided the number of CKM patients age >= 75 years in 2012; the median
      was 45 per unit (interquartile range [IQR], 20-83). The median number of
      symptomatic CKM patients who would otherwise have started dialysis was eight
      (IQR, 4.5-22). CKM practice patterns varied: 35% had a written guideline, 23% had
      dedicated CKM clinics, 45% had dedicated staff, and 50% provided staff training
      on CKM. Most units (88%) provided primary care clinicians with information/advice
      regarding CKM. Eighty percent identified a need for better evidence comparing
      outcomes on CKM versus dialysis, and 65% considered it appropriate to enter
      patients into a randomized trial. CONCLUSIONS: CKM is provided in almost all UK
      renal units, but scale and organization vary widely. Lack of common terminology
      and definitions hinders the development and assessment of CKM. Many survey
      respondents expressed support for further research comparing outcomes with
      conservative care versus dialysis.

PMID- 25388519
TI  - Urinary elafin and kidney injury in hematopoietic cell transplant recipients.
AB  - BACKGROUND AND OBJECTIVES: Graft-versus-host disease (GVHD) is associated with
      kidney injury after hematopoietic cell transplantation (HCT). Because plasma
      elafin levels correlate with skin GVHD, this study examined urinary elafin as a
      potential marker of renal inflammation and injury. DESIGN, SETTING, PARTICIPANTS,
      & MEASUREMENTS: Urine was collected prospectively on 205 patients undergoing
      their first HCT from 2003 to 2010. Collections were done at baseline, weekly
      through day 100, and monthly through year 1 to measure elafin and urine albumin
      to-creatinine ratio (ACR). Associations between urinary elafin levels and
      microalbuminuria, macroalbuminuria, AKI and CKD, and mortality were examined
      using Cox proportional hazards or linear regression models. Available kidney
      biopsy specimens were processed for immunohistochemistry. RESULTS: Mean urinary
      elafin levels to day 100 were higher in patients with micro- or macroalbuminuria
      (adjusted mean difference, 529 pg/ml; P=0.03) at day 100 than in those with a
      normal ACR (adjusted mean difference, 1295 pg/ml; P<0.001). Mean urinary elafin
      levels were higher in patients with AKI compared with patients without AKI
      (adjusted mean difference, 558 pg/ml; P<0.01). The average urinary elafin levels
      within the first 100 days after HCT were higher in patients who developed CKD at
      1 year than in patients without CKD (adjusted mean difference, 894 pg/ml;
      P=0.002). Among allogeneic recipients, a higher proportion of patients with micro
      or macroalbuminuria at day 100 also had grade II-IV acute GVHD (80% and 86%,
      respectively) compared with patients with a normal ACR (58%; global P<0.01). Each
      increase in elafin of 500 pg/ml resulted in a 10% increase in risk of persistent
      macroalbuminuria (hazard ratio, 1.10; 95% confidence interval [95% CI], 1.06 to
      1.13; P<0.001) and a 7% increase in the risk of overall mortality (95% CI, 1.02
      to 1.13, P<0.01). Renal biopsy specimens from a separate cohort of HCT survivors
      demonstrated elafin staining in distal and collecting duct tubules. CONCLUSION:
      Higher urinary elafin levels are associated with an increased risk of micro- and
      macroalbuminuria, AKI and CKD, and death after HCT.

PMID- 25388520
TI  - The relatedness effect on judgments of learning: A closer look at the
      contribution of processing fluency.
AB  - The cue-utilization view to judgments of learning (JOLs) assumes that both ease
      of processing during study and people's beliefs about memory may contribute to
      people's predictions on the likelihood of remembering recently studied
      information. However, a recent study (Mueller, Tauber, & Dunlosky, Psychonomic
      Bulletin & Review, 20(2), 378-384, 2013; Experiment 3) found that processing
      fluency does not contribute to the effect of pair relatedness on JOLs, that is,
      to higher JOLs for related paired associates as compared to unrelated paired
      associates. We investigated whether this finding primarily depends on specific
      aspects of the paired associates employed or on the measure of processing fluency
      used in the previous study. In our first two experiments, participants therefore
      studied lists with (a) uniformly high associative strengths versus (b) a wide
      range of associative strengths. Results showed that processing disfluency-
      operationalized as number of trials to acquisition in Experiment 1 and as self
      paced study time in Experiment 2--partially mediated the effect of relatedness on
      JOLs for both types of lists. Finally, in Experiment 3, the contribution of
      processing fluency to the relatedness effect increased with study-test
      experience. Unlike Mueller et al., we thus found that processing fluency
      contributes to the relatedness effect on JOLs. These findings are consistent with
      the assumption that ease of processing is an important basis for JOLs.

PMID- 25388521
TI  - The roles of long-term phonotactic and lexical prosodic knowledge in phonological
      short-term memory.
AB  - Many previous studies have explored and confirmed the influence of long-term
      phonological representations on phonological short-term memory. In most
      investigations, phonological effects have been explored with respect to
      phonotactic constraints or frequency. If interaction between long-term memory and
      phonological short-term memory is a generalized principle, then other
      phonological characteristics-that is, suprasegmental aspects of phonology-should
      also exert similar effects on phonological short-term memory. We explored this
      hypothesis through three immediate serial-recall experiments that manipulated
      Japanese nonwords with respect to lexical prosody (pitch-accent type, reflecting
      suprasegmental characteristics) as well as phonotactic frequency (reflecting
      segmental characteristics). The results showed that phonotactic frequency
      affected the retention not only of the phonemic sequences, but also of pitch
      accent patterns, when participants were instructed to recall both the phoneme
      sequence and accent pattern of nonwords. In addition, accent pattern typicality
      influenced the retention of the accent pattern: Typical accent patterns were
      recalled more accurately than atypical ones. These results indicate that both
      long-term phonotactic and lexical prosodic knowledge contribute to phonological
      short-term memory performance. 

PMID- 25388522
TI  - Dithiafulvenyl-grafted phenylene ethynylene polymers as selective and reversible
      dispersants for single-walled carbon nanotubes.
AB  - Phenylene ethynylene-based pi-conjugated polymers grafted with dithiafulvenyl
      groups on their side chains were found to be efficient in dispersing single
      walled carbon nanotubes in a selective and controllable way. 

PMID- 25388524
TI  - Enantioselective copper-catalyzed azide-alkyne click cycloaddition to
      desymmetrization of maleimide-based bis(alkynes).
AB  - A copper catalyst system derived from TaoPhos and CuF2 was used successfully for
      catalytic asymmetric Huisgen [3+2] cycloaddition of azides and alkynes to give
      optically pure products containing succinimide- and triazole-substituted
      quaternary carbon stereogenic centers. The desired products were obtained in good
      yields (60-80 %) and 85:15 to >99:1 enantiomeric ratio (e.r.) in this click
      cycloaddition reaction. 

PMID- 25388523
TI  - C11orf95-RELA fusion present in a primary supratentorial ependymoma and recurrent
      sarcoma.
AB  - Ependymomas are rare glial tumors of the central nervous system that arise from
      the cells lining the ventricles and central canal within the spinal cord. The
      distribution of these tumors along the neuroaxis varies by age, most commonly
      involving the spinal cord in adults and the posterior fossa in children. It is
      becoming evident that ependymomas of infratentorial, supratentorial, and spinal
      cord location are genetically distinct which may explain the differences in
      clinical outcomes. A novel oncogenic fusion involving the C11orf95 and RELA genes
      was recently described in supratentorial ependymomas that results in constitutive
      aberrant activation of the nuclear factor-kB signaling pathway. Ependymosarcomas
      are rare neoplasms in which a malignant mesenchymal component arises within an
      ependymoma. We here describe a case of a sarcoma developing in a patient
      previously treated with chemotherapy and radiation whose original ependymoma and
      recurrent sarcoma were both shown to carry the type 1 C11orf95-RELA fusion
      transcript indicating a monoclonal origin for both tumors. 

PMID- 25388525
TI  - Reply: To PMID 25049055.

PMID- 25388526
TI  - Effect of whole-body vibration on calcaneal quantitative ultrasound measurements
      in postmenopausal women: a randomized controlled trial.
AB  - The purpose of this study was to examine the effect of whole-body vibration (WBV)
      on calcaneal quantitative ultrasound (QUS) measurements; which has rarely been
      examined. We conducted a single-centre, 12-month, randomized controlled trial.
      202 postmenopausal women with BMD T score between -1.0 and -2.5, not receiving
      bone medications, were asked to stand on a 0.3 g WBV platform oscillating at
      either 90- or 30-Hz for 20 consecutive minutes daily, or to serve as controls.
      Calcium and vitamin D was provided to all participants. Calcaneal broadband
      attenuation (BUA), speed of sound, and QUS index were obtained as pre-specified
      secondary endpoints at baseline and 12 months by using a Hologic Sahara Clinical
      Bone Sonometer. 12-months of WBV did not improve QUS parameters in any of our
      analyses. While most of our analyses showed no statistical differences between
      the WBV groups and the control group, mean calcaneal BUA decreased in the 90-Hz (
      0.4 [95% CI -1.9 to 1.2] dB MHz(-1)) and 30-Hz (-0.7 [95% CI -2.3 to 0.8] dB MHz(
      1)) WBV groups and increased in the control group (1.3 [95% CI 0.0-2.6] dB MHz(
      1)). Decreases in BUA in the 90-, 30-Hz or combined WBV groups were statistically
      different from the control group in a few of the analyses including all
      randomized participants, as well as in analyses excluding participants who had
      missing QUS measurement and those who initiated hormone therapy or were <80%
      adherent. Although there are consistent trends, not all analyses reached
      statistical significance. 0.3 g WBV at 90 or 30 Hz prescribed for 20 min daily
      for 12 months did not improve any QUS parameters, but instead resulted in a
      statistically significant, yet small, decrease in calcaneal BUA in postmenopausal
      women in several analyses. These unexpected findings require further
      investigation.

PMID- 25388527
TI  - Metabonomic profiling of bladder cancer.
AB  - Early diagnosis and life-long surveillance are clinically important to improve
      the long-term survival of bladder cancer patients. Currently, a noninvasive
      biomarker that is as sensitive and specific as cystoscopy in detecting bladder
      tumors is lacking. Metabonomics is a complementary approach for identifying
      perturbed metabolic pathways in bladder cancer. Significant progress has been
      made using modern metabonomic techniques to characterize and distinguish bladder
      cancer patients from control subjects, identify marker metabolites, and shed
      insights on the disease biology and potential therapeutic targets. With its rapid
      development, metabonomics has the potential to impact the clinical management of
      bladder cancer patients in the future by revolutionizing the diagnosis and life
      long surveillance strategies and stratifying patients for diagnostic, surgical,
      and therapeutic clinical trials. An introduction to metabonomics, typical
      metabonomic workflow, and critical evaluation of metabonomic investigations in
      identifying biomarkers for the diagnosis of bladder cancer are presented. 

PMID- 25388528
TI  - The utility of transoesophageal echocardiography for estimating right ventricular
      systolic pressure.
AB  - With the reduction in use of the pulmonary artery catheter, alternative methods
      of pulmonary pressure estimation are required. The use of echocardiographically
      derived right ventricular systolic pressure has recently been questioned, but
      this technique has not been validated in anaesthetised surgical patients with
      transoesophageal echocardiography. One hundred measurements of right ventricular
      systolic pressure with transoesophageal echocardiography were compared with the
      pulmonary artery systolic pressure obtained simultaneously from a pulmonary
      artery catheter in patients undergoing cardiac surgery. Simultaneous right
      ventricular systolic pressure and pulmonary artery systolic pressure measurements
      were possible in all patients, and these measurements were strongly correlated (r
      = 0.98, p < 0.001), with minimal bias and narrow limits of agreement
      (approximately -5 to +5 mmHg), across a broad range of pulmonary pressures.
      Measurement of right ventricular systolic pressure using tranoesophageal
      echocardiography is readily achievable and closely correlates with pulmonary
      artery systolic pressure, with minimal bias, in cardiac surgical patients
      undergoing general anaesthesia and positive pressure mechanical ventilation of
      the lungs. 

PMID- 25388529
TI  - Development of a chemoradiation therapy toxicity staging system for oropharyngeal
      carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: Develop an innovative tool to standardize representation
      of treatment toxicity and enable shared decision making by mapping provider-based
      outcome descriptions to four overall stages of toxicity from chemoradiation
      therapy for oropharyngeal carcinoma. STUDY DESIGN: Cross-sectional, provider
      based questionnaire. METHODS: Five short-term and five long-term treatment
      outcomes of cisplatin and intensity-modulated radiation therapy for oropharyngeal
      carcinoma were chosen by a focus group of head and neck oncologists. A pilot
      survey was developed in an online platform, and feedback from extramural head and
      neck oncologists was used to refine it for institutional review board submission
      and formal deployment. Respondents were surgical, radiation, and medical
      oncologists with experience in treating oropharyngeal carcinoma. One hundred five
      responses were analyzed, of which 67% were from providers with >10 years in
      practice and 79% were from providers who treat >15 new oropharyngeal carcinoma
      patients per year. RESULTS: A particular overall chemoradiation toxicity class is
      accounted for by two adjoining distress levels (>90% occurrence) for both short
      term and long-term outcomes. Providers deemed mucositis and nausea, and pain and
      xerostomia the most distressing short-term and long-term toxicities,
      respectively. Providers were split as to their impression of the relative
      importance that patients place on short-term versus long-term outcomes when
      considering treatment options. CONCLUSIONS: A clinical tool to represent overall
      chemoradiation toxicity considering short-term and long-term outcomes has been
      developed by analyzing provider-centric responses to a realistic clinical
      scenario. Results from this pilot study enhance patient counseling and shared
      decision making, and serve as foundational information for a prospective,
      longitudinal patient-centric observational study.

PMID- 25388530
TI  - Telocytes damage in endometriosis-affected rat oviduct and potential impact on
      fertility.
AB  - Women with endometriosis (EMs) have unexplained infertility. The recently
      identified telocytes (TCs) might participate in the maintenance of structural and
      functional integrity of oviduct tissue, but so far the involvement of TCs in EMs
      affected oviduct tissue and potential impact on fertility capacity remain
      unknown. By an integrated technique of haematoxylin and eosin staining, in situ
      immunohistochemistry and double-labelled immunofluorescence staining and electron
      microscopy approach, TCs were studied in the autotransplantation Sprague-Dawley
      rat model of EMs-affected oviduct tissue and in sham control, respectively,
      together with determination of iNOS, COX-2, LPO and estradiol. TCs were found in
      perivascular connective tissue and smooth muscle bundles in sham oviduct, with
      typical ultrastructural features (a slender piriform/spindle/triangular cell
      body, and one or more extremely long prolongations, emerged from cell bodies and
      extend to various directions), and specific immunophenotype of CD34
      positive/vimentin-positive/c-kit-negative. However, in EMs-affected oviduct
      tissue (grade III), extensive ultrastructural damage (degeneration, discontinue,
      dissolution and destruction), significant decrease or loss of TCs and
      interstitial fibrosis were observed, together with elevated level of iNOS, COX-2,
      LPO and estradiol, thus suggestive of inflammation and ischaemia-induced TCs
      damage. Based on TCs distribution and intercellular connections, we proposed that
      such damage might be involved in structural and functional abnormalities of
      oviduct, such as attenuated intercellular signalling and oviduct contractility,
      impaired immunoregulation and stem cell-mediated tissue repair, 3-D interstitial
      architectural derangement and tissue fibrosis. Therefore, TCs damage might
      provide a new explanation and potential target for EMs-induced tubal damage and
      fertility disorders. 

PMID- 25388531
TI  - Psychological impact and sexual dysfunction in men with and without spinal cord
      injury.
AB  - INTRODUCTION: The World Health Organization recognizes sexual health as a
      fundamental right that should be guaranteed to all individuals. Sexual
      dysfunction affects various aspects in the lives (physical, psychic, and social)
      of affected persons. AIMS: To assess the different types of sexual dysfunction,
      the quality of life (QOL), depression, anxiety, and levels of self-esteem
      observed in 165 men with sexual dysfunction, both with and without spinal cord
      injury (SCI). METHODS: Case control study of 85 men with SCI and sexual
      dysfunction, and 80 men without SCI that have sexual dysfunction. MAIN OUTCOMES
      MEASURES: The Sexual Health Evaluation Scale, the Fugl-Meyer Life Satisfaction
      Questionnaire scale, the Hospital Anxiety and Depression Scale, the Evaluation of
      the Sexual Health Scale, and Rosenberg's Self-esteem Scale were all used for data
      collection. RESULTS: Of the members in group A (with SCI), 89.4% (76) showed
      erectile dysfunction, and 75.2% (64) reported anejaculation. In group B (without
      SCI), 75 (96.8%) showed erectile dysfunction, and 58.7% (47) had disorders of
      sexual desire. In group A, 16.47 % (14) showed signs of depression, and 35.3%
      (30) had signs of anxiety. In group B, 30% (24) had elevated scores regarding
      depression, and 48.75% (39) had high scores for anxiety. All of the participants
      reported a high general QOL and a high satisfaction with their QOL but reported
      that their satisfaction with their sexual lives was only at the acceptable level.
      Social QOL is significantly higher in the SCI group (t Student P=0.031). The QOL,
      self-esteem, and anxiety and depression levels are significantly correlated.
      CONCLUSIONS: Men with sexual dysfunction strive to adapt to their situations,
      with the relationship between the type of sexual dysfunction and the QOL, mood
      (depression), and self-esteem all being important considerations. Sexuality and
      employment status are the areas where men with spinal cord injuries report less
      satisfaction.

PMID- 25388532
TI  - Editorial: (Thematic Issue: medicinal chemistry of Farnesoid X Receptor (FXR)
      modulators: the-state-of-the-art).

PMID- 25388533
TI  - Medicinal chemistry and pharmacological effects of Farnesoid X Receptor (FXR)
      antagonists.
AB  - The nuclear bile acid sensor farnesoid X receptor (FXR) constitutes a rising
      target for the treatment of a variety of diseases including metabolic disorders,
      inflammation and certain forms of cancer. While the research on FXR agonists has
      yielded many compounds and first clinical candidates, only few FXR antagonists
      have been discovered so far and the knowledge about their in vivo effects is
      quite narrow. We have evaluated available in vitro and in vivo studies with FXR
      antagonists as well as FXR knockout models to elucidate a potential
      pharmacological use of FXR antagonism. To date, the in vitro and in vivo data
      suggests that FXR inhibition by knockout or the use of antagonists causes
      beneficial effects on cholesterol metabolism, ameliorates liver toxicity in
      cholestasis and can reduce the proliferation and migration of some cancer cell
      lines. Unfortunately, also many disadvantageous effects are connected with FXR
      antagonists. 

PMID- 25388534
TI  - Recent advances in non-steroidal FXR antagonists development for therapeutic
      applications.
AB  - Farnesoid X receptor (FXR, NR1H4), a nuclear receptor (NR) highly expressed in
      the liver, intestine, kidney, adrenal glands and other cholesterol-rich tissues,
      functions as the master regulator for bile acid homeostasis. FXR, which regulates
      the expression of genes encoding proteins involved in cholesterol homeostasis,
      plays an essential role in regulating cholesterol, lipid, and glucose metabolism.
      Recently, some FXR agonists are reported to have low selectivity on NRs, which
      forces the researchers to move their eyes onto the development of FXR antagonists
      with high selectivity. The development of non-steroidal FXR antagonists with
      different scaffolds including AGN34, tuberatolides, atractylenolides,
      andrographolides, GW4064 derivatives and 1,3,4-trisubstitutedpyrazolones,
      provides us a prospect for the therapy of in ammation, metabolic syndrome,
      diabetes, cholesterol gallstones, and cancer. 

PMID- 25388535
TI  - Bile acid derivatives as ligands of the farnesoid x receptor: molecular
      determinants for bile acid binding and receptor modulation.
AB  - Bile acids are a peculiar class of steroidal compounds that never cease to amaze.
      From being simple detergents with a primary role in aiding the absorption of fats
      and fat-soluble vitamins, bile acids are now widely considered as crucial
      hormones endowed with genomic and non-genomic functions that are mediated by
      their interaction with several proteins including the nuclear receptor Farnesoid
      X Receptor (FXR). Taking advantages of the peculiar properties of bile acids in
      interacting with the FXR receptor, several biliary derivatives have been
      synthesized and tested as FXR ligands. The availability of these compounds has
      contributed to characterize the receptor from a structural, patho-physiological
      and therapeutic standpoint. Among these, obeticholic acid is a first-in-class FXR
      agonist that is demonstrating hepatoprotective effects upon FXR activation in
      patients with liver diseases such as primary biliary cirrhosis and nonalcoholic
      steatohepatitis. This review provides an historical overview of the rationale
      behind the discovery of obeticholic acid and chemical tools generated to depict
      the molecular features and bio-pharmacological relevance of the FXR receptor, as
      well as to summarize structure-activity relationships of bile acid-based FXR
      ligands so far reported. 

PMID- 25388536
TI  - Knocking on FXR's door: the "hammerhead"-structure series of FXR agonists -
      amphiphilic isoxazoles with potent in vitro and in vivo activities.
AB  - The Farnesoid X Receptor (FXR) was recently validated in clinical studies using
      the bile acid analogue Obeticholic Acid (OCA) as an attractive drug target for
      liver diseases such as Primary Biliary Cirrhosis (PBC) or Non-alcoholic
      Steatohepatitis (NASH). OCA, however, turned out to induce cholesterol- related
      side effects upon prolonged treatment and it shows bile acid like
      pharmacokinetics. The quest for synthetic non-steroidal FXR agonists with general
      drug likeliness and improved pharmacokinetic and - dynamic properties has started
      more than a decade ago: The first non-steroidal and selective FXR agonist with
      decent submicromolar potency, GW4064, was patented in 1998 and published in 2000.
      Since then, many pharmaceutical companies have taken GW4064 as a structural
      template for their efforts in identifying novel patentable FXR agonists with the
      GW-derived trisubstituted isoxazole general structure. However, so far only one
      compound out of these different series has made it into the early stages of
      clinical development: The Px-102/Px-104 from Phenex is currently tested in a
      phase IIa study in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). In
      this review we try to summarize from the patent and scientific literature the
      attempts to improve the GW4064 structure into different directions. Furthermore,
      we suggest directions for further improvements of this special class of synthetic
      FXR agonists which all display the typical "hammerhead"-conformation in the FXR
      ligand binding pocket that provides the basis for their impressive in vitro and
      in vivo potencies. 

PMID- 25388537
TI  - Beyond bile acids: targeting Farnesoid X Receptor (FXR) with natural and
      synthetic ligands.
AB  - The modulation of FXR receptor remains an attractive area in drug discovery to
      develop novel therapeutic opportunities for liver and metabolic disorders.
      Despite the large variety of FXR ligands reported so far, only a very restricted
      number of agonists have entered in clinical settings. In this review article we
      provide the reader with an overview on the different classes of natural and
      synthetic ligands that have been developed by academic groups and pharmaceutical
      companies to target FXR. We discuss their structure-activity relationships,
      analyzing the binding modes that some of these compounds adopt to interact with
      the receptor. 

PMID- 25388538
TI  - Methyltransferases do not work by compression, cratic, or desolvation effects,
      but by electrostatic preorganization.
AB  - The enzyme catechol O-methyltransferase (COMT) catalyzes the transfer of a methyl
      group from S-adenosylmethionine to dopamine and related catechols. The search for
      the origin of COMT catalysis has led to different proposals and hypothesis,
      including the entropic, the NAC, and the compression proposals as well as the
      more reasonable electrostatic idea. Thus, it is important to understand the
      catalytic power of this enzyme and to examine the validity of different proposals
      and in particular the repeated recent implication of the compression idea. The
      corresponding analysis should be done by well-defined physically-based
      considerations that involve computations rather than circular interpretations of
      experimental results. Thus, we explore here the origin of the catalytic
      efficiency of COMT by using the empirical valence bond and the linear response
      approximation approaches. The results demonstrate that the catalytic effect of
      COMT is mainly due to electrostatic preorganization effects. It is also shown
      that the compression, NAC and entropic proposals do not account for the catalytic
      effect.

PMID- 25388539
TI  - Analysis of human plasma lipids by using comprehensive two-dimensional gas
      chromatography with dual detection and with the support of high-resolution time
      of-flight mass spectrometry for structural elucidation.
AB  - The main focus of the present research is the analysis of the unsaponifiable
      lipid fraction of human plasma by using data derived from comprehensive two
      dimensional gas chromatography with dual quadrupole mass spectrometry and flame
      ionization detection. This approach enabled us to attain both mass spectral
      information and analyte percentage data. Furthermore, gas chromatography coupled
      with high-resolution time-of-flight mass spectrometry was used to increase the
      reliability of identification of several unsaponifiable lipid constituents. The
      synergism between both the high-resolution gas chromatography and mass
      spectrometry processes enabled us to attain a more in-depth knowledge of the
      unsaponifiable fraction of human plasma. Additionally, information was attained
      on the fatty acid and triacylglycerol composition of the plasma samples,
      subjected to investigation by using comprehensive two-dimensional gas
      chromatography with dual quadrupole mass spectrometry and flame ionization
      detection and high-performance liquid chromatography with atmospheric pressure
      chemical ionization quadrupole mass spectrometry, respectively. 

PMID- 25388540
TI  - 2-(2-nitrovinyl)furan promotes oxidation of cellular proteins, lipids, and DNA of
      male rat liver and kidney.
AB  - The effect of 2-(2-nitrovinyl)furan on the redox status of male rat liver and
      kidney was evaluated. Twenty male rats were randomized into four groups; group A
      received olive oil and groups B, C, and D rats received 12.5, 25, and 50 mg/kg
      bodyweight of 2-(2-nitrovinyl)furan intraperitoneally, daily at 24 h interval,
      respectively, for 14 days. 2-(2-Nitrovinyl)furan significantly reduced (P < 0.05)
      alkaline phosphatase, alanine, and aspartate aminotransferase activities in male
      rat liver and kidney with a corresponding increase in serum. The activities of
      superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase,
      and levels of reduced glutathione/glutathione disulfide (GSSG) ratio in the liver
      and kidney of 2-(2-nitrovinyl)furan-treated rats decreased significantly (P <
      0.05). In contrast, GSSG, protein carbonyl, conjugated dienes, lipid
      hydroperoxides, malondialdehyde, and fragmented DNA (%) in 2-(2-nitrovinyl)furan
      treated rats increased significantly (P < 0.05). Overall, data from this study
      revealed that 2-(2-nitrovinyl)furan exhibited its toxic effect by suppressing or
      depleting the antioxidant systems. 

PMID- 25388541
TI  - Risk of myocardial infarction in patients receiving testosterone therapy: still a
      matter of debate.

PMID- 25388542
TI  - Apixaban use among patients with severe renal impairment.

PMID- 25388543
TI  - [German version of the de Morton mobility index. First clinical results from the
      process of the cross-cultural adaptation].
AB  - BACKGROUND: The English version of the de Morton Mobility Index (DEMMI) enables
      allied health professions in an inpatient setting to assess the mobility of
      geriatric patients in a reliable, valid, easy and fast way, without showing any
      floor or ceiling effects. The aim of this study was the DEMMI's cross-cultural
      adaption into German language with further analysis of some of its psychometric
      properties based on this process. MATERIAL AND METHODS: Translation was done in a
      multistage procedure following international recommendations. Within clinical
      pilot testing the DEMMI was routinely applied over a period of 3 weeks in a
      geriatric hospital. User experiences were evaluated in a qualitative way and
      DEMMI test results were analyzed with the focus on practicability and
      responsiveness. RESULTS: A German DEMMI version has been translated and performed
      with 133 patients. The test takes approximately 10 min to administer, is save and
      easy to use and does not show any floor or ceiling effects. The DEMMI is valid
      for the whole mobility spectrum, that is why mobility changes can be realized
      sufficiently in contrast to the Timed Up And Go Test. CONCLUSION: The DEMMI is
      already applicable in the German-speaking world. However, further research on its
      validity and reproducibility are desirable.

PMID- 25388544
TI  - [Nursing homes versus assisted living facilities: Outcome quality regarding
      pressure ulcers, falls and malnutrition].
AB  - BACKGROUND: Assisted living has become more popular among individuals who are
      care-dependent or are threatened with care dependency as an attractive
      alternative to a standard nursing home. As differences regarding nursing care
      quality in both settings are so far unknown, the aim of the study was to compare
      the quality indicators occurrence of pressure ulcers, falls and malnutrition in
      both settings. MATERIAL AND METHODS: In spring 2010 a multicentre cross-sectional
      study on the prevalence of care problems was conducted including 3610 individuals
      in 31 nursing homes (NH) and 21 assisted living facilities (ALF) following a
      standardized study protocol. Comparative analyses of raw and adjusted prevalence
      of the care problems occurrence of pressure ulcers, falls and malnutrition were
      conducted. RESULTS: Individuals in the ALFs were on average older than those in
      the NHs (89.5 years vs. 83.2 years) but were more mobile and less care-dependent.
      The prevalence of care problems in the NHs compared to those in the ALFs showed
      the following results: pressure ulcers (NH = 3.9%, ALF = 2.3%), nosocomial
      pressure ulcer prevalence (NH = 2.3%, ALF = 0.2%), incidence of falls within 3
      months (NH = 12.5%, ALF = 20.4%) and malnutrition according to a body mass index
      (BMI) <= 18.5 kg/m(2) (NH = 5.6%, ALF = 11.4%). CONCLUSION: Due to the population
      differences, no final conclusions about the quality of care according to the
      analysed indicators can be made. While the prevalence of pressure ulcers was
      remarkably lower, falls and malnutrition had a higher prevalence in ALFs. Ongoing
      and systematic outcome quality surveys in different long-term care facilities are
      recommended.

PMID- 25388545
TI  - Statistical significance of hair analysis of clenbuterol to discriminate
      therapeutic use from contamination.
AB  - Clenbuterol is a well-established beta2-agonist, which is prohibited in sports
      and strictly regulated for use in the livestock industry. During the last few
      years clenbuterol-positive results in doping controls and in samples from
      residents or travellers from a high-risk country were suspected to be related the
      illegal use of clenbuterol for fattening. A sensitive liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method was developed to detect low
      clenbuterol residues in hair with a detection limit of 0.02 pg/mg. A sub
      therapeutic application study and a field study with volunteers, who have a high
      risk of contamination, were performed. For the application study, a total dosage
      of 30 ug clenbuterol was applied to 20 healthy volunteers on 5 subsequent days.
      One month after the beginning of the application, clenbuterol was detected in the
      proximal hair segment (0-1 cm) in concentrations between 0.43 and 4.76 pg/mg. For
      the second part, samples of 66 Mexican soccer players were analyzed. In 89% of
      these volunteers, clenbuterol was detectable in their hair at concentrations
      between 0.02 and 1.90 pg/mg. A comparison of both parts showed no statistical
      difference between sub-therapeutic application and contamination. In contrast,
      discrimination to a typical abuse of clenbuterol is apparently possible. Due to
      these findings results of real doping control samples can be evaluated.

PMID- 25388546
TI  - The E3 ubiquitin ligase RNF121 is a positive regulator of NF-kappaB activation.
AB  - BACKGROUND: The nuclear factor kappaB (NF-kappaB) family members regulate several
      biological processes as cell proliferation and differentiation, inflammation,
      immunity and tumor progression. Ubiquitination plays a key role in NF-kappaB
      activation and the ubiquitylated transmitters of the NF-kappaB signaling cascade
      accumulate in close proximity to endomembranes. FINDINGS: We performed an
      unbiased siRNA library screen targeting the 46 E3 ubiquitin ligases bearing
      transmembrane domains to uncover new modulators of NF-kappaB activation, using
      tumor necrosis factor-alpha (TNF-alpha) receptor (TNFR) stimulation as a model.
      We report here the identification of a new Golgi Apparatus-resident protein,
      RNF121, as an enhancer of NF-kappaB promoter activity through the catalytic
      function of its RING domain. From a molecular standpoint, while knocking down
      RNF121 did not alter RIP1 ubiquitination and IKK activation, the proteasomal
      degradation of IkappaBalpha was impaired suggesting that this E3 ubiquitin ligase
      regulates this process. However, RNF121 did not directly ubiquitinate
      IkappaBalpha While they were found in the same complex. Finally, we discovered
      that RNF121 acts as a broad regulator of NF-kappaB signaling since its silencing
      also dampens NF-kappaB activation following stimulation of Toll-Like Receptors
      (TLRs), Nod-Like Receptors (NLRs), RIG-I-Like Receptors (RLRs) or after DNA
      damages. CONCLUSIONS: These results unveil an unexpected role of Golgi Apparatus
      and reveal RNF121 as a new player involved in the signaling leading to NF-kappaB
      activation.

PMID- 25388547
TI  - Hospital Ethics Committees in Poland.
AB  - According to UNESCO guidelines, one of the four forms of bioethics committees in
      medicine are the Hospital Ethics Committees (HECs). The purpose of this study was
      to evaluate how the above guidelines are implemented in real practice. There were
      111 hospitals selected out of 176 Polish clinical hospitals and hospitals
      accredited by Center of Monitoring Quality in Health System. The study was
      conducted by the survey method. There were 56 (50%) hospitals that responded to
      the survey. The number of HECs members fluctuated between 3 and 16 members, where
      usually 5 (22% of HECs) members were part of the board committee. The composition
      of the HECs for professions other than physicians was diverse and non
      standardized (nurses-in 86% of HECs, clergy-42%, lawyers-38%, psychologists-28%,
      hospital management-23%, rehab staff-7 %, patient representatives-3%, ethicists
      2%). Only 55% of HECs had a professional set of standards. 98% of HECs had
      specific tasks. 62% of HECs were asked for their expertise, and 55% prepared
      <6.88% of the opinions were related to interpersonal relations between hospital
      personnel, patients and their families with emphasis on the interactions between
      superiors and their inferiors or hospital staff and patients and their families.
      Only 12% of the opinions were reported by the respondents as related to ethical
      dilemmas. In conclusion, few Polish hospitals have HECs, and the structure,
      services and workload are not always adequate. To ensure a reliable operation of
      HECs requires the development of relevant legislation, standard operating
      procedures and well trained members.

PMID- 25388548
TI  - Complex lipids.

PMID- 25388549
TI  - Cognitive profile of patients with glycogen storage disease type III: a clinical
      description of seven cases.
AB  - BACKGROUND: Glycogen storage disease type III (GSDIII) is a rare autosomal
      recessive disorder due to glycogen debranching enzyme (GDE) deficiency. It
      results in a multisystemic disease with predominant hepatic and myopathic
      symptoms. While frequent social maladjustment has been observed in our clinical
      practice, cognitive and psychological disturbances have never been assessed. The
      aim of this pilot study was to examine and characterize the cognitive profile of
      patients with GSDIII. METHODS: Seven patients (six women and one man, mean age:
      38.7 +/- 11.6 years) with GSDIII underwent a neuropsychological set of tests
      assessing global cognitive efficiency, executive functions, social cognition,
      apathy, and episodic memory. RESULTS: All patients presented previous
      psychopathological history. We observed attention fluctuations for each patient,
      and impaired global cognitive efficiency with deficiencies in executive functions
      in 5/7 patients. Emotional skills (social cognition) were impaired in five
      patients. Memory was mostly preserved. CONCLUSION: The impairment in social
      cognition (recognition of emotions and ability to attribute mental states to
      others) and executive functions observed could be a consequence of orbito-frontal
      dysfunction due to the abnormal glycogen metabolism characteristic of the
      underlying disease. These results are consistent with the hypothesis of a central
      nervous system involvement in patients with GSDIII, but need to be confirmed in
      future research. This could explain the social and economic difficulties, and the
      lack of compliance to the medical follow-up presented by these patients. It
      suggests that these disturbances need to be taken into account when planning the
      medical management of patients with GSDIII.

PMID- 25388550
TI  - Co-occurrence of the Poland sequence in a patient with the cobalamin C defect:
      more than just a coincidence?

PMID- 25388551
TI  - Oral health of elite athletes and association with performance: a systematic
      review.
AB  - BACKGROUND: We aimed to systematically review the epidemiology of oral disease
      and trauma in the elite athlete population and to investigate the impact of oral
      health on sporting performance. METHODS: Authors searched Ovid MEDLINE (1950 to
      October 2013), Ovid EMBASE (1980 to October 2013), EBSCO SPORTDiscus (up to
      October 2013) and OpenGrey (http://www.opengrey.eu). No date or language
      restrictions were applied. Papers were included if they evaluated the oral health
      of professional athletes. The methodological quality of papers was evaluated
      using a modification of the Newcastle-Ottawa scale. RESULTS: The literature
      search led to 9858 potentially relevant citations. Following a set of predefined
      exclusion criteria, 34 studies remained. Twenty-six studies reported on dental
      trauma, which ranged in prevalence from 14% to 47% varying by sport and country.
      Sixteen studies considered the oral health of athletes and reported high
      prevalence of oral diseases: dental caries 15-75%, dental erosion 36-85%,
      periodontal disease 15%. In four studies, a range between 5% and 18% of athletes
      reported negative impact of oral health or trauma on performance. The
      methodological quality of included studies was generally low. CONCLUSIONS: Within
      the limits of the review, oral health of athletes is poor. We hypothesise that
      poor oral health associates with self-reported performance; however, this needs
      to be tested. Further studies on representative samples of athletes are needed to
      assess the size of the problem of poor oral health as well as to investigate the
      possible impact on performance using objective measures of performance.

PMID- 25388552
TI  - Exercise during school hours when added to patient education improves outcome for
      2 years in adolescent patellofemoral pain: a cluster randomised trial.
AB  - BACKGROUND: Patellofemoral pain (PFP) is common among adolescents and associated
      with long-lasting pain and disability. Patient education and exercise therapy are
      commonly used treatments in primary and secondary care but the effect of these
      treatments in adolescents is unknown. We aimed to determine the effect of
      exercise therapy as an add-on therapy to patient education compared with
      education alone. METHODS: 121 adolescents from 15-19 years of age were cluster
      randomised to patient education or patient education combined with exercise
      therapy. Patient education covered self-management of pain and information on
      PFP. Exercise therapy consisted of supervised exercises on school premises
      (3/week for 3 months) and instructions on home-based exercises. Adherence to
      exercises was assessed as attendance and weekly text messages. Primary outcome
      measure was self-reported recovery (seven-point Likert scale) at 12 months with
      additional follow-ups at 3, 6 and 24 months. RESULTS: Adolescents randomised to
      patient education and exercise therapy were more likely to have recovered at 12
      months (OR, 1.73, 95% CI 1.02 to 2.93, number needed to treat (NNT) of 11).
      Similar results were observed at 3 and 6 months (OR 1.88 and 1.43) while the
      effect was further increased at 24 months (OR of 2.52, NNT of 5). A higher total
      number of weekly exercise sessions increased the odds of recovery. CONCLUSIONS:
      In adolescent PFP, the addition of exercise therapy for 3 months was more
      effective than patient education alone. The effect was apparent at 3 months and
      increased up to 2 years. Adherence to exercises was important and improved the
      odds of recovery. TRIAL REGISTRATION NUMBER: clinicaltrials.gov reference:
      NCT01438762.

PMID- 25388553
TI  - Effect of growth factors and steroid hormones on heme oxygenase and cyclin D1
      expression in primary astroglial cell cultures.
AB  - Astrocyte activity may be modulated by steroid hormones and GFs. This study
      investigates the interaction between glucocorticoids or estrogens and GFs on the
      expression of heme oxygenase-1 (HO-1) and cyclin D1 in astrocyte cultures at 14
      days treated for 48 or 60 hr with dexamethasone (DEX) or 48 hr with 17beta
      estradiol (E2) alone or with GFs added only in the last 12 or 24 hr. Twelve- or
      twenty-four-hour epidermal growth factor (EGF) treatment significantly enhanced
      HO-1 expression in astrocyte cultures pretreated for 48 hr with DEX. A highly
      significant increase in HO-1 expression was obtained after the last-12-hr EGF
      treatment in 48-hr E2-pretreated astrocyte cultures; this enhancement was
      particularly significant in 48-hr E2-pretreated cultures as well as in the last
      12-hr insulin-treated ones pretreated for 48 hr with E2. Sixty-hour DEX-alone
      pretreatment as well as the last-12-hr EGF treatment in 60-hr DEX-pretreated
      astrocyte cultures showed a significant increase of cyclin D1 expression. A
      significant decrease of cyclin D1 expression in the last-12-hr insulin-like
      growth factor-I (IGF-1)-treated cultures pretreated for 60 hr with DEX was
      observed. A highly significant enhancement in cyclin D1 expression in 14 days in
      vitro astrocyte cultures pretreated with E2 alone for 48 hr and treated in the
      last 12 hr with IGF-1 in 48-hr E2-pretreated cultures was found. Finally, the
      data highlight an interactive dialogue between the growth factors and
      glucocorticoids or estrogens during the maturation of astroglial cells in culture
      that may control the HO-1 and cyclin D1 expression as well as proliferating
      astroglial cells during the cell cycle.

PMID- 25388554
TI  - Effects of UV radiation on aquatic ecosystems and interactions with other
      environmental factors.
AB  - Interactions between climate change and UV radiation are having strong effects on
      aquatic ecosystems due to feedback between temperature, UV radiation, and
      greenhouse gas concentration. Higher air temperatures and incoming solar
      radiation are increasing the surface water temperatures of lakes and oceans, with
      many large lakes warming at twice the rate of regional air temperatures. Warmer
      oceans are changing habitats and the species composition of many marine
      ecosystems. For some, such as corals, the temperatures may become too high.
      Temperature differences between surface and deep waters are becoming greater.
      This increase in thermal stratification makes the surface layers shallower and
      leads to stronger barriers to upward mixing of nutrients necessary for
      photosynthesis. This also results in exposure to higher levels of UV radiation of
      surface-dwelling organisms. In polar and alpine regions decreases in the duration
      and amount of snow and ice cover on lakes and oceans are also increasing exposure
      to UV radiation. In contrast, in lakes and coastal oceans the concentration and
      colour of UV-absorbing dissolved organic matter (DOM) from terrestrial ecosystems
      is increasing with greater runoff from higher precipitation and more frequent
      extreme storms. DOM thus creates a refuge from UV radiation that can enable UV
      sensitive species to become established. At the same time, decreased UV radiation
      in such surface waters reduces the capacity of solar UV radiation to inactivate
      viruses and other pathogens and parasites, and increases the difficulty and price
      of purifying drinking water for municipal supplies. Solar UV radiation breaks
      down the DOM, making it more available for microbial processing, resulting in the
      release of greenhouse gases into the atmosphere. In addition to screening solar
      irradiance, DOM, when sunlit in surface water, can lead to the formation of
      reactive oxygen species (ROS). Increases in carbon dioxide are in turn acidifying
      the oceans and inhibiting the ability of many marine organisms to form UV
      absorbing exoskeletons. Many aquatic organisms use adaptive strategies to
      mitigate the effects of solar UV-B radiation (280-315 nm), including vertical
      migration, crust formation, synthesis of UV-absorbing substances, and enzymatic
      and non-enzymatic quenching of ROS. Whether or not genetic adaptation to changes
      in the abiotic factors plays a role in mitigating stress and damage has not been
      determined. This assessment addresses how our knowledge of the interactive
      effects of UV radiation and climate change factors on aquatic ecosystems has
      advanced in the past four years. 

PMID- 25388555
TI  - Direct injection method for HPLC/MS/MS analysis of acrylamide in aqueous
      solutions: application to adsorption experiments.
AB  - Polyacrylamides are polymers used in many fields and represent the main source of
      release of the highly toxic acrylamide in the environment. In this work, a
      simple, rapid, and sensitive analytical method was developed with HPLC/MS/MS and
      direct injection for acrylamide analysis in water and adsorption samples. AFNOR
      standards NF T90-210 and NF T90-220 were used for the analytical method
      validation and uncertainty estimation. Limit of quantification (LOQ) for
      acrylamide was 1 MUg/L, and accuracy was checked at three acrylamide levels (1,
      6, and 10 MUg/L). Uncertainties were estimated at 34.2, 22, and 12.4 % for
      acrylamide concentrations at LOQ, 6 MUg/L, and 10 MUg/L, respectively. Acrylamide
      adsorption on clays (kaolinite, illite) and sludge was then studied as a function
      of pH, time, and acrylamide concentrations. Acrylamide adsorption on kaolinite,
      illite, and sludge was found to be very weak since adsorption percentages were
      inferior to 10 %, whatever the pH value and the initial acrylamide concentration.
      The low affinity of acrylamide for clays and sludge is likely due to its
      hydrophilic property, small size, and charge neutrality.

PMID- 25388556
TI  - Improvement on species sensitivity distribution methods for deriving site
      specific water quality criteria.
AB  - Species sensitivity distribution (SSD) is the most common method used to derive
      water quality criteria, but there are still issues to be resolved. Here, issues
      associated with application of SSD methods, including species selection, plotting
      position, and cutoff point setting, are addressed. A preliminary improvement to
      the SSD approach based on post-stratified sampling theory is proposed. In the
      improved method, selection of species is based on biota of a specific basin, and
      the whole species in the specific ecosystem are considered. After selecting
      species to be included and calculating the cumulative probability, a new method
      to set the critical threshold for protection of ecosystem-level structure and
      function is proposed. The alternative method was applied in a case study in which
      a water quality criterion (WQC) was derived for ammonia in the Songhua River
      (SHR), China. 

PMID- 25388557
TI  - Immobilization of Cd in paddy soil using moisture management and amendment.
AB  - To offer scientific data support for remediation of Cd-contaminated paddy soils
      under reasonable water condition, pot experiment was conducted to study the
      effects of moisture management and amendments on Cd immobilization in a paddy
      soil. Application of biochar combined with organic fertilizer reduced the
      exchangeable Cd by 20.4, 15.7, and 13.0% and brown rice Cd by 43.8, 35.5, and
      42.1% under continuous flooding, conventional irrigation, and wetting irrigation,
      respectively, compared to the controls. Under no amendments, the content of
      Fe(II) in root coating in the continuous flooding treatment was 2.3 and 3.6 times
      of that in the conventional and wetting irrigation treatments, but Cd in root
      coating in the continuous flooding treatment was only 82.6 and 73.8% of that in
      the conventional and wetting irrigation treatments. Applying amendments increased
      the Fe(II) in root coating by 27.3, 59.1, and 65.0% but reduced the Cd in root
      coating by 33.6, 26.5, and 25.1% under continuous flooding, conventional
      irrigation, and wetting irrigation, respectively. The lower bioavailability of Cd
      in paddy soil and the competition for adsorption sites in root coating of rice
      plant between Cd(2+) and Fe(2+) reduced from bivalent ions jointly caused the
      lower brown rice Cd in amended soils.

PMID- 25388558
TI  - 2,3,7,8-TCDD-mediated toxicity in peripheral blood mononuclear cells is
      alleviated by the antioxidants present in Gelidiella acerosa: an in vitro study.
AB  - Seaweeds have been used as a source of traditional medicine worldwide for the
      treatment of various ailments, mainly due to their ability to quench the free
      radicals. The present study aims at evaluating the protective effect of
      methanolic extract of Gelidiella acerosa, an edible red seaweed against 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced toxicity in peripheral blood
      mononuclear cells (PBMC). For evaluating the protective effect of G. acerosa,
      PBMC were divided into four groups: vehicle control, TCDD (10 nM), TCDD + G.
      acerosa (300 MUg/ml), and G. acerosa alone treated. Scavenging of intracellular
      reactive oxygen species (ROS) induced by TCDD was assessed by the dichloro
      dihydro-fluorescein diacetate (DCFH-DA) method. Alterations at macromolecular
      level were quantified through lipid peroxidation (LPO) level, protein carbonyl
      content (PCC) level, and comet assay. The cellular morphology upon TCDD toxicity
      and G. acerosa treatment was obtained by light microscopy and histopathological
      studies. The chemical composition present in the methanolic extract of G. acerosa
      was determined by gas chromatography-mass spectrometry (GC-MS) analysis. The
      results reveal that 10 nM TCDD caused significant (P < 0.05) reduction in cell
      viability (94.10 +/- 0.99), and treatment with 300 MUg/ml extract increased the
      cell viability (99.24 +/- 0.69). TCDD treatment resulted in a significant
      increase in the production of ROS, LPO (114 +/- 0.09), and PCC (15.13 +/- 1.53)
      compared to the control, whereas co-treatment with G. acerosa significantly (P <
      0.05) mitigated the effects. Further, G. acerosa significantly (P < 0.05)
      prevented TCDD-induced genotoxicity and cell damage. GC-MS analysis showed the
      presence of n-hexadecanoic acid (retention time (RT) 13.15), cholesterol (RT
      28.80), alpha-D-glucopyranose, 4-O-alpha-D-galactopyranosyl (RT 20.01), and
      azulene (RT 4.20). The findings suggest that G. acerosa has a strong protective
      ability against TCDD-induced cytotoxicity, oxidative stress, and DNA damage.

PMID- 25388559
TI  - Long-term effects of drinking-water treatment residuals on dissolved phosphorus
      export from vegetated buffer strips.
AB  - The export of dissolved phosphorus (P) in surface runoff from agricultural land
      can lead to water quality degradation. Surface application of aluminium (Al)
      based water treatment residuals (Al-WTRs) to vegetated buffer strip (VBS) soils
      can enhance P removal from surface runoff during single runoff events. However,
      the longer-term effects on P removal in VBSs following application of products
      such as Al-WTR remain uncertain. We used field experimental plots to examine the
      long-term effects of applying a freshly generated Al-WTR to VBSs on dissolved P
      export during multiple runoff events, occurring between 1 day and 42 weeks after
      the application of Al-WTR. Vegetated buffer strip plots amended with Al-WTR
      significantly reduced soluble reactive P and total dissolved P concentrations in
      surface runoff compared to both unamended VBS plots and control plots. However,
      the effectiveness of Al-WTR decreased over time, by approximately 70% after 42
      weeks compared to a day following Al-WTR application. Reduced performance did not
      appear to be due to drying of Al-WTR in the field. Instead, the development of
      preferential flow paths as well as burying of Al-WTR with freshly deposited
      sediments may explain these observations. Better understanding of the processes
      controlling long-term P removal by Al-WTR is required for effective management of
      VBSs.

PMID- 25388560
TI  - Extractive and oxidative removal of copper bound to humic acid in soil.
AB  - Copper (Cu) is often found strongly bound to natural organic matter (NOM) in soil
      through the formation of strong Cu-NOM complexes. Therefore, in order to
      successfully remediate Cu-contaminated soils, effective removal of Cu bound to
      soil organic matter should be considered. In this study, we investigated soil
      washing methods for Cu removal from a synthetic Cu-contaminated model silica soil
      coated with humic acid (HA) and from field contaminated soil. Various reagents
      were studied to extract Cu bound to NOM, which included oxidant (H2O2), base
      (NaOH), and chelating agents (citric acid and ethylenediaminetetraacetic acid
      (EDTA)). Among the wash reagents, EDTA extracted Cu most effectively since EDTA
      formed very strong complexes with Cu, and Cu-HA complexes were transformed into
      Cu-EDTA complexes. NaOH extracted slightly less Cu compared to EDTA. HA was
      effectively extracted from the model soil under strongly alkaline conditions with
      NaOH, which seemed to concurrently release Cu bound to HA. However, chemical
      oxidation with H2O2 was not effective at destroying Cu-HA complexes. Fourier
      transform infrared spectroscopy and elemental analysis revealed that chelating
      agents such as citrate and EDTA were adsorbed onto the model soil via possible
      complexation between HA and extraction agents. The extraction of Cu from a field
      contaminated soil sample was effective with chelating agents, while oxidative
      removal with H2O2 and extractive removal with NaOH separated negligible amounts
      of Cu from the soil. Based on these results, Cu bound to organic matter in soil
      could be effectively removed by chelating agents, although remnant agents may
      remain in the soil. 

PMID- 25388561
TI  - Influence of nitrogen loading and plant nitrogen assimilation on nitrogen
      leaching and N2O emission in forage rice paddy fields fertilized with liquid
      cattle waste.
AB  - Livestock wastewater disposal onto rice paddy fields is a cost- and labor
      effective way to treat wastewater and cultivate rice crops. We evaluated the
      influence of nitrogen loading rates on nitrogen assimilation by rice plants and
      on nitrogen losses (leaching and N2O emission) in forage rice fields receiving
      liquid cattle waste (LCW). Four forage rice fields were subjected to nitrogen
      loads of 107, 258, 522, and 786 kg N ha(-1) (N100, N250, N500, and N750,
      respectively) using basal fertilizer (chemical fertilizer) (50 kg N ha(-1)) and
      three LCW topdressings (each 57-284 kg N ha(-1)). Nitrogen assimilated by rice
      plants increased over time. However, after the third topdressing, the nitrogen
      content of the biomass did not increase in any treatment. Harvested aboveground
      biomass contained 93, 60, 33, and 31 % of applied nitrogen in N100, N250, N500,
      and N750, respectively. The NH4 (+) concentration in the pore water at a depth of
      20 cm was less than 1 mg N L(-1) in N100, N250, and N500 throughout the
      cultivation period, while the NH4 (+) concentration in N750 increased to 3 mg N
      L(-1) after the third topdressing. Cumulative N2O emissions ranged from -0.042 to
      2.39 kg N ha(-1); the highest value was observed in N750, followed by N500. In
      N750, N2O emitted during the final drainage accounted for 80 % of cumulative N2O
      emissions. This study suggested that 100-258 kg N ha(-1) is a recommended
      nitrogen loading rate for nitrogen recovery by rice plants without negative
      environmental impacts such as groundwater pollution and N2O emission.

PMID- 25388562
TI  - Uncoupling of microbial community structure and function in decomposing litter
      across beech forest ecosystems in Central Europe.
AB  - The widespread paradigm in ecology that community structure determines function
      has recently been challenged by the high complexity of microbial communities.
      Here, we investigate the patterns of and connections between microbial community
      structure and microbially-mediated ecological function across different forest
      management practices and temporal changes in leaf litter across beech forest
      ecosystems in Central Europe. Our results clearly indicate distinct pattern of
      microbial community structure in response to forest management and time. However,
      those patterns were not reflected when potential enzymatic activities of microbes
      were measured. We postulate that in our forest ecosystems, a disconnect between
      microbial community structure and function may be present due to differences
      between the drivers of microbial growth and those of microbial function. 

PMID- 25388564
TI  - Improving science through improved acknowledgment of reviewers.

PMID- 25388567
TI  - Experimental and computed phase diagrams of the Fe-Re system.
AB  - In order to clarify controversial reports on the Fe-Re phase diagram, a new
      experimental investigation has been carried out. Three intermetallic phases have
      been evidenced, including the new report of the P phase found for the first time
      in a binary system. The phase relations involving the sigma phase were
      established. In parallel, a first-principles study has been performed which
      provided the heat of formation of every ordered configuration for four
      intermetallic phases (D8(b), A12, A13 and P). The mixing energy of solid
      solutions (fcc, bcc, hcp) was calculated using the special quasi-random structure
      method. Calculations were performed with the help of the density functional
      theory, with and without spin polarization. From these results, in the frame of
      the Compound Energy Formalism using the Bragg-Williams approximation, the Fe-Re
      phase diagram has been computed without the use of adjustable parameters.
      Different thermodynamic parameters obtained experimentally and theoretically, as
      the site occupancies, are compared. The computed phase diagram presents several
      differences with the experimental one. To understand these differences, the
      influence of several parameters on the phase stability, such as the magnetic
      contribution has been evaluated.

PMID- 25388563
TI  - A pragmatic, multicentre, randomised controlled trial comparing stapled
      haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease
      (eTHoS): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Current interventions for haemorrhoidal disease include traditional
      haemorrhoidectomy (TH) and stapled haemorrhoidopexy (SH) surgery. However,
      uncertainty remains as to how they compare from a clinical, quality of life (QoL)
      and economic perspective. The study is therefore designed to determine whether SH
      is more effective and more cost-effective, compared with TH. METHODS/DESIGN:
      eTHoS (either Traditional Haemorrhoidectomy or Stapled Haemorrhoidopexy for
      Haemorrhoidal Disease) is a pragmatic, multicentre, randomised controlled trial.
      Currently, 29 secondary care centres are open to recruitment. Patients, aged 18
      year or older, with circumferential haemorrhoids grade II to IV, are eligible to
      take part. The primary clinical and economic outcomes are QoL profile (area under
      the curve derived from the EuroQol Group's 5 Dimension Health Status
      Questionnaire (EQ-5D) at all assessment points) and incremental cost per quality
      adjusted life year (QALY) based on the responses to the EQ-5D at 24 months. The
      secondary outcomes include a comparison of the SF-36 scores, pain and symptoms
      sub-domains, disease recurrence, complication rates and direct and indirect costs
      to the National Health Service (NHS). A sample size of n =338 per group has been
      calculated to provide 90% power to detect a difference in the mean area under the
      curve (AUC) of 0.25 standard deviations derived from EQ-5D score measurements,
      with a two-sided significance level of 5%. Allowing for non-response, 400
      participants will be randomised per group. Randomisation will utilise a
      minimisation algorithm that incorporates centre, grade of haemorrhoidal disease,
      baseline EQ-5D score and gender. Blinding of participants and outcome assessors
      is not attempted. DISCUSSION: This is one of the largest trials of its kind. In
      the United Kingdom alone, 29,000 operations for haemorrhoidal disease are done
      annually. The trial is therefore designed to give robust evidence on which
      clinicians and health service managers can base management decisions and, more
      importantly, patients can make informed choices. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN80061723 (assigned 8 March 2010).

PMID- 25388568
TI  - The accurate calculation of the band gap of liquid water by means of GW
      corrections applied to plane-wave density functional theory molecular dynamics
      simulations.
AB  - Knowledge about the intrinsic electronic properties of water is imperative for
      understanding the behaviour of aqueous solutions that are used throughout
      biology, chemistry, physics, and industry. The calculation of the electronic band
      gap of liquids is challenging, because the most accurate ab initio approaches can
      be applied only to small numbers of atoms, while large numbers of atoms are
      required for having configurations that are representative of a liquid. Here we
      show that a high-accuracy value for the electronic band gap of water can be
      obtained by combining beyond-DFT methods and statistical time-averaging. Liquid
      water is simulated at 300 K using a plane-wave density functional theory
      molecular dynamics (PW-DFT-MD) simulation and a van der Waals density functional
      (optB88-vdW). After applying a self-consistent GW correction the band gap of
      liquid water at 300 K is calculated as 7.3 eV, in good agreement with recent
      experimental observations in the literature (6.9 eV). For simulations of phase
      transformations and chemical reactions in water or aqueous solutions whereby an
      accurate description of the electronic structure is required, we suggest to use
      these advanced GW corrections in combination with the statistical analysis of
      quantum mechanical MD simulations. 

PMID- 25388569
TI  - [The central sensory organ and its disturbances].

PMID- 25388570
TI  - [Nascent chromatin composition revealed].

PMID- 25388571
TI  - [Kinetic regulation of pre-messenger RNA alternative splicing].

PMID- 25388572
TI  - [Prefrontal parvalbumin-expressing interneurons control fear behavior].

PMID- 25388573
TI  - [Sickle cell disease: pneumococcus escapes prevention and adapts to the disease.
      Consequences on vaccine design].

PMID- 25388574
TI  - [Ever more humanized mice for new therapeutic applications].

PMID- 25388575
TI  - [3D revolution of stem cells: in vitro generation of ear sensory epithelia].

PMID- 25388576
TI  - [Elongation of the axoneme and dynamics of intraflagellar transport].
AB  - Cilia and flagella are essential organelles in most eukaryotes including human
      beings. In this review, we will discuss the mode of assembly of these complex
      organelles that depends on a dynamic process called intraflagellar transport or
      IFT. IFT delivers structural elements at the distal end of the cilium where
      assembly takes place, thereby allowing the growth of the organelle. We next
      discuss the different models for control of cilium length and their alterations
      in ciliopathies, genetic diseases associated to ciliary defects. 

PMID- 25388577
TI  - [The ciliary pocket: a rendezvous between the centrosome and vesicular
      trafficking].
AB  - The assembly of cilia, ciliogenesis, involves complex and conserved mechanisms
      during which the basal body has to dock onto cell membranes. Studies in the 1960s
      suggested that in many cell types such docking occurs in the cytoplasm and that
      cilia are formed within a vesicle before being delivered to the plasma membrane.
      This intracellular pathway, recently characterized at the molecular level, leads
      to the formation of a membrane domain at the basis of cilia, the ciliary pocket,
      which was involved in vesicular trafficking and signaling. 

PMID- 25388578
TI  - [Transcriptional control of ciliary genes].
AB  - Cilia are found in many eukaryotic species and share a common microtubule
      architecture that can nonetheless show very diverse features within one animal.
      The genesis of cilia and their diversity require the expression of different
      specific genes. At least two classes of transcription factors are involved in
      ciliogenesis: the RFX family, essential for the assembly of most cilia and the
      FOXJ1 transcription factors that are key regulators of motile cilia assembly.
      These two different families of transcription factors have both specific and
      common target genes and they can also cooperate for the formation of cilia. In
      collaboration with cell type specific factors, they also contribute to the
      specialisation of cilia. As a consequence, the identification of RFX and FOXJ1
      target genes has emerged as an efficient strategy to identify novel ciliary
      genes, and in particular genes potentially implicated in ciliopathies. 

PMID- 25388579
TI  - [Interplay between primary cilia and cell cycle].
AB  - The primary cilium is often associated with the phases G0 and G1 of the cellular
      cycle in most of the cells. So, recent studies show that its formation and its
      resorption are closely linked to molecular actors of the cellular cycle, as for
      example Aurora A or PLK1 (polo-like kinase 1). Furthermore, its resorption seems
      to be critical for the progress of the phase S and the cellular determination, in
      particular in the case of neural stem cells. Finally, the primary cilium acts as
      a cellular antenna allowing to transmit numerous signal pathways which, in their
      turn, contribute to the cellular fate. 

PMID- 25388580
TI  - [Primary cilia control different steps of brain development].
AB  - The role of primary cilia in adult neurons remains elusive, however their
      developmental functions during brain morphogenesis have been recently highlighted
      thanks to mouse models. Unmistakably, they are needed for Hedgehog (Hh)-dependent
      patterning in the forebrain. Not only for Hh reception itself, but most
      importantly for a downstream event in the Hh transduction pathway, independent of
      Hh ligand: the Gli3 processing. Indeed, phenotypes due to cilia disruption in the
      developing brain, such as early patterning, olfactory bulb or corpus callosum
      formation, can be rescued by reintroducing Gli3-R (the short truncated form of
      Gli3 working as a transcriptional repressor of Hh target gene). In addition,
      primary cilia control the proliferation rate in different neural progenitors in
      the cortex, the hippocampus and the cerebellum; they are required for proper
      migration of interneurons. And cilia dysfunction is correlated with hydrocephaly,
      synaptogenesis defects and aberrant axonal tract projections. Most of these
      neurodevelopmental defects can be related to the various neurological features
      frequently observed across the ciliopathy spectrum. And thus, understanding the
      underlying mechanisms of these diverse functions of primary cilia in the brain is
      a new fundamental challenge. 

PMID- 25388581
TI  - [Cilia and neuronal migrations].
AB  - In a landmark paper published in 1977, G. Albrecht-Buehler described a primary
      cilium on the surface of migrating fibroblasts, and noticed that cilia are
      oriented parallel to the direction of migration of fibroblasts. While the
      presence of a primary cilium on neural progenitors and on post-mitotic neurons
      was noted long ago, it has been observed on migrating cortical interneurons only
      recently. As in fibroblasts, the cilium of interneurons controls the
      directionality of migration. It plays an important role in the reorientation of
      cortical interneurons towards the cortical plate. The morphogen Shh, which is
      expressed in the migratory pathway of interneurons, is one of the signals that
      control this reorientation. 

PMID- 25388582
TI  - [Cilia and heart morphogenesis].
AB  - After the seminal discovery in 2000 that primary cilia are functional organelles
      which are essential for embryonic development, several mouse models of
      ciliopathies have been generated. The heart is frequently affected, with a large
      spectrum of malformations. The cilia of the node are required early in
      development in the determination of the left/right laterality of the embryo,
      which has secondary consequences on the formation of the heart. Thus, abnormal
      looping of the heart is a recurrent phenotype in models of ciliopathies. However,
      the function of primary cilia in cardiac cells remains poorly understood.
      Receptors such as polycystins or hedgehog receptors are usually localized in the
      primary cilium, raising the possibility that these signalling pathways, which are
      important for the septation and the growth of the heart, are transduced in
      primary cilia of cardiac cells. Knowledge of the roles of primary cilia at
      different steps of heart development and in different cardiac cell types will be
      essential to better understand the origin of human cardiopathies associated with
      ciliopathies. 

PMID- 25388583
TI  - [The multiple links between cilia and planar cell polarity].
AB  - Since our seminal study in 2003, much has been written about core planar cell
      polarity (core PCP) signaling and the inner ear. In just a few years, and using
      the inner ear as a model system, our understanding of the molecular basis of this
      signaling pathway and how it can influence the development of tissues in mammals
      has increased considerably. Recently, a number of studies using various animal
      models of development have uncovered original relationships between the cilia and
      PCP, and the study of the hair cells of the inner ear has helped elucidating one
      of these links. In this review, we highlight the differences of PCP signaling
      between mammals and invertebrates. In the light of recent results, we sum up our
      current knowledge about PCP signaling in the mammalian cochlear epithelium and we
      discuss the impact of recent data in the field. We focus our attention on the
      interrelationship between asymmetric polarity complexes and the position of the
      cilium, which is essential for the establishment of the overall tissue polarity. 

PMID- 25388584
TI  - [Genetic complexity of ciliopathies and novel genes identification].
AB  - Ciliopathies are a large group of human disorders caused by dysfunction of
      primary or motile cilia and unified by their overlapping clinical features (brain
      malformations, retinal dystrophy, cystic kidney disease, liver fibrosis and
      skeletal abnormalities). Ciliopathies are mendelian disorders with prominent
      genetic heterogeneity and marked allelism between different clinical entities,
      which are in part explained by the recently identified functional modules and
      multi-protein complexes formed by ciliopathy-associated gene products. The
      current review provides an updated snapshot of this complex evolving field,
      highlighting the key phenotypic features and causative genes for commonly-studied
      ciliopathies and summarizing our emerging understanding of the correlations
      between the functions of subgroups of genes and clinical sub-types of
      ciliopathies. Using the example of Joubert syndrome, a ciliopathy characterized
      by a distinctive hindbrain malformation and caused by mutations in more than 20
      different genes, this work also reviews the principal methods used for new gene
      identification, including candidate gene approaches, homozygosity mapping as well
      as high throughput next-generation and exome sequencing. 

PMID- 25388585
TI  - [Cilia and renal cysts].
AB  - Advances in genomics, bioinformatics and the creation of model organisms have
      identified many genes associated with polycystic kidney diseases. Historically,
      these genes were not necessarily associated with ciliopathies, but it appeared
      that many connections can be made between the cystic kidney disease and function
      of the primary cilium. Indeed, the proteins encoded by these genes are localized
      to the cilium itself, to the basal body or are known to regulate the expression
      and localization of ciliary proteins. The goal of this article is to describe the
      multiple cellular processes that may lead to the development of renal cysts if
      they are deregulated. These include changes in proliferation rate, cell polarity
      or signaling pathways involved in embryonic kidney development. To highlight the
      role of the primary cilium in cystogenesis, I will discuss several studies
      investigating the function of ciliary genes and cilia in the kidneys of different
      model organisms. 

PMID- 25388586
TI  - [Bardet-Biedl syndrome: cilia and obesity - from genes to integrative
      approaches].
AB  - The primary cilium is a specialized organelle, present at the surface of most
      eukaryotic cells, whose main function is to detect, integrate and transmit intra-
      and extra-cellular signals. Its dysfunction usually results in a group of severe
      clinical manifestations nowadays termed ciliopathies. The latter can be of
      syndromic nature with multi-organ dysfunctions and can also be associated with a
      morbid obese phenotype, like it is the case in the iconic ciliopathy, the Bardet
      Biedl syndrome (BBS). This review will discuss the contribution of the unique
      context offered by the emblematic BBS for understanding the mechanisms leading to
      obesity via the involvement of the primary cilium together with identification of
      novel molecular players and signaling pathways it has helped to highlight. In the
      current context of translational medicine and system biology, this article will
      also discuss the potential benefits and challenges posed by these techniques via
      multi-level approaches to better dissect the underlying mechanisms leading to the
      complex condition of obesity. 

PMID- 25388587
TI  - [Non-ciliary functions of cilia proteins].
AB  - Cilia proteins have long been characterized for their role in cilia formation and
      function, and their implications in ciliopathies. However, several cellular
      defects induced by cilia proteins deregulation suggest that they could have non
      ciliary roles. Indeed, several non-ciliary functions have been recently
      characterized for cilia proteins including roles in intra-cellular and in
      vesicular transport, in spindle orientation or in the maintenance of genomic
      stability. These observations thus raise the crucial question of the contribution
      of non-ciliary functions of cilia proteins to the pathological manifestations
      associated with ciliopathies such as polycystic kidney disease. 

PMID- 25388589
TI  - iPathCons and iPathDB: an improved insect pathway construction tool and the
      database.
AB  - Insects are one of the most successful animal groups on earth. Some insects, such
      as the silkworm and honeybee, are beneficial to humans, whereas others are
      notorious pests of crops. At present, the genomes of 38 insects have been
      sequenced and made publically available. In addition, the transcriptomes of
      dozens of insects have been sequenced. As gene data rapidly accumulate,
      constructing the pathway of molecular interactions becomes increasingly important
      for entomological research. Here, we developed an improved tool, iPathCons, for
      knowledge-based construction of pathways from the transcriptomes or the official
      gene sets of genomes. Considering the high evolution diversity in insects,
      iPathCons uses a voting system for Kyoto Encyclopedia of Genes and Genomes
      Orthology assignment. Both stand-alone software and a web server of iPathCons are
      provided. Using iPathCons, we constructed the pathways of molecular interactions
      of 52 insects, including 37 genome-sequenced and 15 transcriptome-sequenced ones.
      These pathways are available in the iPathDB, which provides searches, web server,
      data downloads, etc. This database will be highly useful for the insect research
      community. Database URL: http://ento.njau.edu.cn/ipath/ 

PMID- 25388590
TI  - Genetic polymorphisms of phase I and phase II metabolic enzymes as modulators of
      lung cancer susceptibility.
AB  - OBJECTIVES: Tobacco exposure remains the main etiologic factor for lung cancer
      (LC). Interactions between environment and individual genetic profile are
      particularly important for this disease. The aim of this study was to evaluate
      the contribution of CYP1A1*2A, CYP1A1*2C, CYP2D6*4, GSTP1, GSTM1, GSTT1 and NAT2
      polymorphisms for the susceptibility to LC in a Portuguese population considering
      their demographic and clinical characteristics. MATERIALS AND METHODS: A total of
      200 LC and 247 controls subjects from the Centre of Portugal were studied.
      Clinical and demographic characteristics were collected from clinical files and
      by individual questionnaires. Polymorphisms of CYP1A1*2A, CYP1A1*2C, CYP2D6*4,
      GSTP1, GSTM1, GSTT1 and NAT2 were genotyped using PCR-RFLP, PCR multiplex, ARMS
      and real time. RESULTS: Gender, family history of cancer, smoke cessation and
      alcohol consumption were independent risk factors (p < 0.05). Associations found
      between phases I and II genes and LC population reveal a sex dependent
      distribution. Logistic regression analysis demonstrates that enhanced activation
      by CYPs, associated by reduced or loss of function of phase II enzymes, can lead
      to a greater risk. GSTP1 and NAT2 polymorphisms studied have a significant
      contribution for the histological tumour types and the presence of metastases, at
      time of diagnosis, respectively, when males with smoking habits were considered.
      CONCLUSION: Multiple interactions between environment and individual
      characteristics are clearly associated to this disease. Variants of the
      detoxification genes may act synergistically contributing to this disease and
      modifying the risk posed by smoking and sex. The GSTT1*0 and GSTP1 (Ile462Val)
      might contribute to the malignant phenotype through different mechanisms.

PMID- 25388591
TI  - Height and kidney cancer risk: a meta-analysis of prospective studies.
AB  - PURPOSE: The aim of this study was to perform a meta-analysis to summarize the
      available evidence from prospective studies on the association between height and
      kidney cancer risk. METHODS: Relevant studies were identified through the MEDLINE
      and EMBASE databases up to July 2014, as well as through the references from the
      retrieved articles. Relative risks (RRs) from individual studies were pooled by
      using a random-effects model. RESULTS: A total of fourteen prospective studies of
      adult height and kidney cancer risk with 18,766 cases were included in the meta
      analysis. Overall, per 10-cm increase in height was associated with an increased
      risk of kidney cancer (RR 1.23; 95 % confidence interval 1.18-1.28, I(2) = 11.8
      %). Subgroup analysis showed a basically consistent result with the overall
      analysis. There was no evidence of publication bias. CONCLUSIONS: High adult
      height was positively associated with the risk of kidney cancer in both men and
      women in this meta-analysis. Future prospective studies are needed to determine
      the generalizability of these findings to non-Caucasians.

PMID- 25388592
TI  - School social capital and body mass index in the National Longitudinal Study of
      Adolescent Health.
AB  - BACKGROUND: Social capital in neighborhoods and workplaces positively affects
      health. Less is known about the influence of school social capital on student
      health outcomes, in particular weight status. We sought to examine the
      association between individual- and school-level social capital and student body
      mass index (BMI). METHODS: Analyzing data from the National Longitudinal Study of
      Adolescent Health, a nationally representative sample of adolescents in grades 7
      12 (N = 13,428), we used principal components analysis to define 3 school social
      capital factors: "connectedness" (feel part of/close to people/safe in school),
      "treatment" (get along with teachers/students, teachers treat students fairly),
      and "parental involvement" (school administrator reported percent family/parent
      self-reported participation in Parent Teacher Organization, average daily school
      attendance). We examined the associations between individual- and school-level
      social capital and individual BMI using multilevel modeling techniques. RESULTS:
      In girls, both feeling connected to one's school (beta = -0.06, p < .05) and
      attending schools with overall high connectedness (b = -0.43, p < .01) were
      associated with lower BMIs. In boys only attending a school with high "treatment"
      was inversely associated with BMI (b = -0.61, p < .01), adjusting for individual
      and school demographics. CONCLUSIONS: Although further studies are needed, our
      findings suggest enhancing school social capital as a novel approach to
      addressing student obesity.

PMID- 25388593
TI  - Higher weight, lower education: a longitudinal association between adolescents'
      body mass index and their subsequent educational achievement level?
AB  - BACKGROUND: The purpose of this study was to examine the association between
      adolescents' body mass index (BMI) z-scores and their subsequent level of
      schooling, extending previous longitudinal research by using objectively measured
      weight and height data. METHODS: A longitudinal study with 3 study waves (1-year
      intervals) involving 1248 Dutch adolescents (49% girls; mean age = 13.7 years) at
      schools providing different educational levels was used to determine adolescents
      who moved and did not move to a lower educational level in the first year, or in
      the second year, and to examine whether this movement could be predicted by BMI z
      scores (zBMI), after controlling for a large range of potential confounding
      factors. RESULTS: A total of 1164 Dutch adolescents continued in the same level
      of education, whereas 84 adolescents moved to a lower educational level (43 moved
      in the first and 41 in the second year). A higher zBMI significantly increased
      the risk of a general transition to a lower educational level, and of a
      transition in the first year, but not in the second year, after controlling for
      potential demographic, behavioral, and psychological confounds. CONCLUSIONS:
      Findings suggest that a higher zBMI during adolescence immediately lowers
      educational achievement level during general secondary education.

PMID- 25388594
TI  - Food and beverage promotions in Minnesota secondary schools: secular changes,
      correlates, and associations with adolescents' dietary behaviors.
AB  - BACKGROUND: The purpose of this study was to describe promotions for unhealthy
      and healthy foods and beverages within Minnesota secondary schools from 2008 to
      2012, and to examine associations with school-level coordination of environmental
      improvements and students' dietary behaviors. METHODS: The Minnesota School
      Health Profiles and Minnesota Student Survey data were used along with National
      Center for Education Statistics data to conduct analyses accounting for school
      level demographics. RESULTS: There was no significant improvement over time in
      the proportion of schools that banned advertising for unhealthy products in
      school buildings, on school grounds, on buses, or in publications. Whereas more
      than two thirds of schools had implemented strategies focused on the promotion of
      fruits/vegetables by 2012, only 37% labeled healthful foods with appealing names
      and just 17% used price incentives to encourage healthy choices. The number of
      stakeholders representing different roles on school health councils was
      positively correlated with implementation of healthy food and beverage promotion
      strategies. Little evidence was found to support an influence of in-school
      advertising bans or promotions on students' diets. CONCLUSIONS: Policy changes
      are needed to protect students from food and beverage advertising and additional
      opportunities exist to reduce disparities in the selection of healthy options at
      school.

PMID- 25388595
TI  - Using a participatory approach to the development of a school-based physical
      activity policy in an Indigenous community.
AB  - BACKGROUND: This study is part of a larger community-based participatory research
      (CBPR) project to develop, implement, and evaluate the physical activity
      component of a school-based wellness policy. The policy intervention is being
      carried out by community stakeholders and academic researchers within the
      Kahnawake Schools Diabetes Prevention Project, a well-established health
      promotion organization in the Indigenous community of Kahnawake, Quebec. METHODS:
      We explored how a group of stakeholders develop a school physical activity policy
      in a participatory manner, and examined factors serving as facilitators and
      barriers to the development process. This case study was guided by an
      interpretive description approach and draws upon data from documentary analysis
      and participant observation. RESULTS: A CBPR approach allowed academic
      researchers and community stakeholders to codevelop a physical activity policy
      that is both evidence-based and contextually appropriate. The development process
      was influenced by a variety of barriers and facilitators including working within
      existing structures, securing appropriate stakeholders, and school contextual
      factors. CONCLUSIONS: This research offers a process framework that others
      developing school-based wellness policies may use with appropriate modifications
      based on local environments.

PMID- 25388596
TI  - Effectiveness of the IMPACT:Ability program to improve safety and self-advocacy
      skills in high school students with disabilities.
AB  - BACKGROUND: Individuals with disabilities experience higher rates of abuse than
      the nondisabled. Few evidence-based prevention interventions have been published
      despite a need for such work. This study evaluated IMPACT: Ability, a safety and
      self-advocacy training for individuals with cognitive and/or physical
      disabilities. METHODS: A quasi-experimental design was used to assess change in
      safety and self-advocacy knowledge, confidence, and behaviors among special
      education high school students in Boston, MA. Instruments were interviewer
      administered at 3 time points. Analysis of covariance (ANCOVA) was used to
      compare change between the intervention (N = 21) and wait-list (N = 36) groups.
      Repeated measures analysis was used to test change in the complete sample (N =
      57). RESULTS: Students were diverse (58% males, 82% nonwhite) with a range of
      disabilities. Significantly greater improvement in key outcomes, including safety
      and self-advocacy knowledge, confidence, and behavior, were observed in
      intervention students compared to the wait-list group. Results in the complete
      sample showed evidence of further improvements in students' sense of safety and
      general self-efficacy. CONCLUSIONS: These findings are encouraging given the
      effects were demonstrated in a heterogeneous urban population. IMPACT: Ability
      may be an effective safety and self-advocacy training for students with
      disabilities. Further research will be required to determine effectiveness within
      particular subpopulations of students.

PMID- 25388598
TI  - No safe haven: locations of harassment and bullying victimization in middle
      schools.
AB  - BACKGROUND: Given that adolescent bullying victimization is a significant concern
      for secondary education and adolescent development, identifying school contexts
      in which victimization is most likely to occur is salient. METHODS: An anonymous
      online survey assessed the prevalence of being harassed or bullied in various
      locations within 20 middle schools (grades 5-9) in New Jersey and New York (N =
      10,668). Seven types of bullying-related victimization (teased in an unfriendly
      way, called hurtful names, physically abused, excluded from a group to hurt
      feelings, belongings taken/damaged, threatened to be hurt, and negative rumors
      spread) were examined in 7 locations where each type of victimization could occur
      (classroom, lunchroom, hallways, gym, playground, bus, or bathroom). RESULTS:
      Prevalence of victimization types ranged from 4% to 38% depending on location.
      Prevalence of overall victimization was equal or greater in classrooms compared
      with other school locations (highest prevalence rates in hallways, classrooms,
      and lunchrooms), regardless of school demographic characteristics. Victimization
      in classrooms compared with other school settings was most highly associated with
      feelings of being unsafe. CONCLUSIONS: Vigilant attention to bullying is needed
      across all school environments and especially in the classroom context, which may
      mistakenly be perceived as a more protected area. Indeed, middle school
      classrooms are not safe havens.

PMID- 25388597
TI  - Perceptions of oral health, preventive care, and care-seeking behaviors among
      rural adolescents.
AB  - BACKGROUND: An asymmetrical oral disease burden is endured by certain population
      subgroups, particularly children and adolescents. Reducing oral health
      disparities requires understanding multiple oral health perspectives, including
      those of adolescents. This qualitative study explores oral health perceptions and
      dental care behaviors among rural adolescents. METHODS: Semistructured individual
      interviews with 100 rural, minority, low socioeconomic status adolescents
      revealed their current perceptions of oral health and dental care access.
      Respondents age ranged from 12 to 18 years. The sample was 80% black and 52%
      male. RESULTS: Perceived threat from dental disease was low. Adolescents
      perceived regular brushing and flossing as superseding the need for preventive
      care. Esthetic reasons were most often cited as reasons to seek dental care.
      Difficulties accessing dental care include finances, transportation, fear, issues
      with Medicaid coverage and parental responsibility. In general, adolescents and
      their parents are in need of information regarding the importance of preventive
      dental care. CONCLUSIONS: Findings illuminate barriers to dental care faced by
      low-income rural adolescents and counter public perceptions of government
      sponsored dental care programs as being "free" or without cost. The importance of
      improved oral health knowledge, better access to care, and school-based dental
      care is discussed.

PMID- 25388599
TI  - Measuring the youth bullying experience: a systematic review of the psychometric
      properties of available instruments.
AB  - BACKGROUND: Bullying is a significant problem in schools and measuring this
      concept remains problematic. The purposes of this study were to (1) identify the
      published self-report measures developed to assess youth bullying; (2) evaluate
      their psychometric properties and instrument characteristics; and (3) evaluate
      the quality of identified psychometric papers evaluating youth bullying measures.
      METHODS: A systematic review of the literature was conducted using 4 electronic
      databases. Data extraction and appraisal of identified instruments were completed
      using a standardized method and Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) guidelines. RESULTS: Thirty-one articles describing 27
      self-report instruments were evaluated in our analysis. Quality assessments
      ranged from 18% to 91%, with 6 papers reaching or exceeding a quality score of
      75%. Limited evidence supporting the reliability, validity, and responsiveness of
      existing youth bullying measures was identified. CONCLUSIONS: Evidence supporting
      the psychometric soundness of the instruments identified was limited. Many
      measures were in early development and additional evaluation is necessary to
      validate their psychometric properties. A pool of instruments possesses
      acceptable initial psychometric dependability for selected assessment purposes.
      These findings have significant implications for assessing youth bullying and
      designing and evaluating school-based interventions.

PMID- 25388600
TI  - Additional postcranial elements of Teilhardina belgica: the oldest European
      primate.
AB  - Teilhardina belgica is one of the earliest fossil primates ever recovered and the
      oldest fossil primate from Europe. As such, this taxon has often been
      hypothesized as a basal tarsiiform on the basis of its primitive dental formula
      with four premolars and a simplified molar cusp pattern. Until recently [see Rose
      et al.: Am J Phys Anthropol 146 (2011) 281-305; Gebo et al.: J Hum Evol 63 (2012)
      205-218], little was known concerning its postcranial anatomy with the exception
      of its well-known tarsals. In this article, we describe additional postcranial
      elements for T. belgica and compare these with other tarsiiforms and with
      primitive adapiforms. The forelimb of T. belgica indicates an arboreal primate
      with prominent forearm musculature, good elbow rotational mobility, and a
      horizontal, rather than a vertical body posture. The lateral hand positions imply
      grasps adaptive for relatively large diameter supports given its small body size.
      The hand is long with very long fingers, especially the middle phalanges. The
      hindlimb indicates foot inversion capabilities, frequent leaping, arboreal
      quadrupedalism, climbing, and grasping. The long and well-muscled hallux can be
      coupled with long lateral phalanges to reconstruct a foot with long grasping
      digits. Our phyletic analysis indicates that we can identify several postcranial
      characteristics shared in common for stem primates as well as note several
      derived postcranial characters for Tarsiiformes.

PMID- 25388601
TI  - Keratitis by Fusarium temperatum, a novel opportunist.
AB  - BACKGROUND: Fusarium species are among the most common fungi present in the
      environment and some species have emerged as major opportunistic fungal infection
      in human. However, in immunocompromised hosts they can be virulent pathogens and
      can cause death. The pathogenesis of this infection relies on three factors:
      colonization, tissue damage, and immunosuppression. A novel Fusarium species is
      reported for the first time from keratitis in an agriculture worker who acquired
      the infection from plant material of maize. Maize plants are the natural host of
      this fungus where it causes stalk rot and seeding malformation under temperate
      and humid climatic conditions. The clinical manifestation, microbiological
      morphology, physiological features and molecular data are described. METHODS:
      Diagnosis was established by using polymerase chain reaction of fungal DNA
      followed by sequencing portions of translation elongation factor 1 alpha (TEF1
      alpha) and beta-tubulin (BT2) genes. Susceptibility profiles of this fungus were
      evaluated using CLSI broth microdilution method. RESULTS: The analyses of these
      two genes sequences support a novel opportunist with the designation Fusarium
      temperatum. Phylogenetic analyses showed that the reported clinical isolate was
      nested within the Fusarium fujikuroi species complex. Antifungal susceptibility
      testing demonstrated that the fungus had low MICs of micafungin (0.031 MUg/ml),
      posaconazole (0.25 MUg/ml) and amphotericin B (0.5 MUg/ml). CONCLUSION: The
      present case extends the significance of the genus Fusarium as agents of
      keratitis and underscores the utility of molecular verification of these emerging
      fungi in the human host.

PMID- 25388602
TI  - Two butenolides with PPARalpha agonistic activity from a marine-derived
      Streptomyces.

PMID- 25388603
TI  - Systematic review comparing the safety and efficacy of conventional and drug
      eluting bead transarterial chemoembolization for inoperable hepatocellular
      carcinoma.
AB  - AIM: Conventional transarterial chemoembolization (cTACE) is widely used for
      treating patients with inoperable hepatocellular carcinoma (HCC). A variation on
      the technique based on drug-eluting beads (DEB-TACE) has recently entered the
      clinic, but trials of its safety and efficacy have given conflicting results.
      This systematic review aimed to gain a current, comprehensive picture of how DEB
      TACE compares with cTACE. METHODS: MEDLINE, EMBASE, the Cochrane Library, the
      Chinese National Knowledge Infrastructure database and clinical trial registries
      were searched through June 2014. Risk ratios (RR), hazard ratios (HR) and 95%
      confidence intervals (CI) were calculated. RESULTS: The analysis included four
      randomized controlled trials, one uncontrolled prospective study and one
      prospective case-control study, altogether involving 652 patients. Overall
      survival benefit was similar between cTACE and DEB-TACE patients (HR = 1.07, 95%
      CI = 0.82-1.40, P = 0.875). However, DEB-TACE was associated with a significantly
      higher objective tumor response rate (RR = 1.14, 95% CI = 1.01-1.29, P = 0.03)
      and a slightly lower incidence of adverse events. CONCLUSION: Though the
      available evidence suggests that although DEB-TACE is associated with better
      tumor response and potentially fewer adverse events, it does not provide greater
      survival benefit than cTACE. These results need to be validated in high-quality
      trials with large sample size.

PMID- 25388605
TI  - The medicinal chemistry of bioterrorism.

PMID- 25388606
TI  - Obsessive-compulsive and related disorders in ICD-11.

PMID- 25388608
TI  - Body dysmorphic disorder and olfactory reference disorder: proposals for ICD-11.
AB  - The article reviews the historical background and symptoms of body dysmorphic
      disorder (BDD) and olfactory reference disorder, and describes the proposals of
      the WHO ICD-11 Working Group on the Classification of Obsessive-Compulsive and
      Related Disorders related to these categories. This paper examines the possible
      classification of BDD symptoms in ICD-10. Four different possible diagnoses are
      found (hypochondriacal disorder, schizotypal disorder, delusional disorder, or
      other persistent delusional disorder). This has led to significant confusion and
      lack of clear identification in ICD-10. Olfactory reference disorder can also be
      classified as a delusional disorder in ICD-10, but there is no diagnosis for non
      delusional cases. The Working Group reviewed the classification and diagnostic
      criteria of BDD in DSM-5, as well as cultural variations of BDD and olfactory
      reference disorder that include Taijin Kyofusho. The Working Group has proposed
      the inclusion of both BDD and olfactory reference disorder in ICD-11, and has
      provided diagnostic guidelines and guidance on differential diagnosis. The
      Working Group's proposals for ICD-11 related to BDD and olfactory reference
      disorder are consistent with available global evidence and current understanding
      of common mechanisms in obsessive-compulsive and related disorders, and resolve
      considerable confusion inherent in ICD-10. The proposals explicitly recognize
      cultural factors. They are intended to improve clinical utility related to
      appropriate identification, treatment, and resource allocation related to these
      disorders. 

PMID- 25388607
TI  - Obsessive-compulsive disorder for ICD-11: proposed changes to the diagnostic
      guidelines and specifiers.
AB  - Since the approval of the ICD-10 by the World Health Organization (WHO) in 1990,
      global research on obsessive-compulsive disorder (OCD) has expanded dramatically.
      This article evaluates what changes may be needed to enhance the scientific
      validity, clinical utility, and global applicability of OCD diagnostic guidelines
      in preparation for ICD-11. Existing diagnostic guidelines for OCD were compared.
      Key issues pertaining to clinical description, differential diagnosis, and
      specifiers were identified and critically reviewed on the basis of the current
      literature. Specific modifications to ICD guidelines are recommended, including:
      clarifying the definition of obsessions (i.e., that obsessions can be thoughts,
      images, or impulses/urges) and compulsions (i.e., clarifying that these can be
      behaviors or mental acts and not calling these "stereotyped"); stating that
      compulsions are often associated with obsessions; and removing the ICD-10
      duration requirement of at least 2 weeks. In addition, a diagnosis of OCD should
      no longer be excluded if comorbid with Tourette syndrome, schizophrenia, or
      depressive disorders. Moreover, the ICD-10 specifiers (i.e., predominantly
      obsessional thoughts, compulsive acts, or mixed) should be replaced with a
      specifier for insight. Based on new research, modifications to the ICD-10
      diagnostic guidelines for OCD are recommended for ICD-11. 

PMID- 25388609
TI  - Hypochondriasis: considerations for ICD-11.
AB  - The World Health Organization (WHO) is currently revisiting the ICD. In the 10th
      version of the ICD, approved in 1990, hypochondriacal symptoms are described in
      the context of both the primary condition hypochondriacal disorder and as
      secondary symptoms within a range of other mental disorders. Expansion of the
      research base since 1990 makes a critical evaluation and revision of both the
      definition and classification of hypochondriacal disorder timely. This article
      addresses the considerations reviewed by members of the WHO ICD-11 Working Group
      on the Classification of Obsessive-Compulsive and Related Disorders in their
      proposal for the description and classification of hypochondriasis. The proposed
      revision emphasizes the phenomenological overlap with both anxiety disorders
      (e.g., fear, hypervigilance to bodily symptoms, and avoidance) and obsessive
      compulsive and related disorders (e.g., preoccupation and repetitive behaviors)
      and the distinction from the somatoform disorders (presence of somatic symptom is
      not a critical characteristic). This revision aims to improve clinical utility by
      enabling better recognition and treatment of patients with hypochondriasis within
      the broad range of global health care settings. 

PMID- 25388610
TI  - Hoarding disorder: a new diagnostic category in ICD-11?
AB  - Despite the long-held view that hoarding is a symptom of both obsessive
      compulsive disorder and obsessive-compulsive personality disorder, increased
      evidence has emerged during the last 20 years suggesting that hoarding represents
      a distinct form of psychopathology. This study reflects the discussions on the
      nosological status of hoarding carried out by the WHO ICD-11 Working Group on the
      Classification of Obsessive-Compulsive and Related Disorders. The distinctiveness
      of hoarding is based on its having core symptoms that differ from those of other
      disorders, as well as distinctive neurobiological correlates and treatment
      responses. Furthermore, data showing the clinical utility, global applicability,
      and appropriateness of the concept of hoarding disorder outside specialty mental
      health settings suggest that this condition should be included in ICD-11.
      Finally, given the focus of ICD-11 on primary care and public health, the Working
      Group suggests that poor insight and severe domestic squalor may be considered as
      specifiers for hoarding disorder in ICD-11. 

PMID- 25388611
TI  - Obsessive-compulsive (anankastic) personality disorder: toward the ICD-11
      classification.
AB  - Obsessive-compulsive personality disorder (OCPD) is an early-onset disorder
      characterized by perfectionism, need for control, and cognitive rigidity. Its
      nosological status is currently under review. Historically, OCPD has been
      conceptualized as bearing a close relationship with obsessive-compulsive disorder
      (OCD). In this article, we discuss the diagnosis of OCPD in anticipation of its
      review for the ICD-11, from the perspective of clinical utility, global
      applicability, and research planning. Considering the recent establishment of an
      obsessive-compulsive and related disorders (OCRD) category in DSM-5, we focus on
      the relationship between OCPD and the disorders that are currently thought to
      bear a close relationship with OCD, including DSM-5 OCRD, and other compulsive
      disorders such as eating disorder and autistic spectrum disorder (that were not
      included in the DSM-5 OCRD category), as well as with the personality disorders,
      focusing on nosological determinants such as phenomenology, course of illness,
      heritability, environmental risk factors, comorbidity, neurocognitive
      endophenotypes, and treatment response. Based on this analysis, we attempt to
      draw conclusions as to its optimal placement in diagnostic systems and draw
      attention to key research questions that could be explored in field trials. 

PMID- 25388612
TI  - Tourette and tic disorders in ICD-11: standing at the diagnostic crossroads.
AB  - This article reflects discussion by the WHO ICD-11 Working Group on the
      Classification of Obsessive-Compulsive and Related Disorders. After reviewing the
      historical classification of tic disorders, this article discusses their
      placement in ICD-11. Existing problems with diagnostic labels and criteria,
      appropriate placement of the tic disorders category within the ICD-11 system, and
      pragmatic factors affecting classification are reviewed. The article ends with
      recommendations to (a) maintain consistency with the DSM-5 diagnostic labels for
      tic disorders, (b) add a minimum duration guideline for a provisional tic
      disorder diagnosis, (c) remove the multiple motor tic guideline for the diagnosis
      of Tourette disorder, and (d) co-parent the tic disorder diagnoses in the
      disorders of the nervous system and the mental and behavioral disorders
      categories, with secondary co-parenting in the obsessive-compulsive and related
      disorders and neurodevelopmental disorders sections. 

PMID- 25388613
TI  - Body-focused repetitive behavior disorders in ICD-11.
AB  - This article addresses the question of how body-focused repetitive behavior
      disorders (e.g., trichotillomania and skin-picking disorder) should be
      characterized in ICD-11. The article reviews the historical nosology of the two
      disorders and the current approaches in DSM-5 and ICD-10. Although data are
      limited and mixed regarding the optimal relationship between body-focused
      repetitive behavior disorders and nosological categories, these conditions should
      be included within the obsessive-compulsive and related disorders category, as
      this is how most clinicians see these behaviors, and as this may optimize
      clinical utility. The descriptions of these disorders should largely mirror those
      in DSM-5, given the evidence from recent field surveys. The recommendations
      regarding ICD-11 and body-focused repetitive behavior disorders should promote
      the global identification and treatment of these conditions in primary care
      settings. 

PMID- 25388614
TI  - Stereotyped movement disorder in ICD-11.
AB  - According to current proposals for ICD-11, stereotyped movement disorder will be
      classified in the grouping of neurodevelopmental disorders, with a qualifier to
      indicate whether self-injury is present, similar to the classification of
      stereotypic movement disorder in DSM-5. At the same time, the WHO ICD-11 Working
      Group on the Classification of Obsessive-Compulsive and Related Disorders has
      proposed a grouping of body-focused repetitive behavior disorders within the
      obsessive-compulsive and related disorders (OCRD) cluster to include
      trichotillomania and skin-picking disorder. DSM-5 has taken a slightly different
      approach: trichotillomania and excoriation (skin picking) disorder are included
      in the OCRD grouping, while body-focused repetitive behavior disorder is listed
      under other specified forms of OCRD. DSM-5 also includes a separate category of
      nonsuicidal self-injury in the section on "conditions for further study." There
      are a number of unresolved nosological questions regarding the relationships
      among stereotyped movement disorder, body-focused repetitive behavior disorders,
      and nonsuicidal self-injury. In this article, we attempt to provide preliminary
      answers to some of these questions as they relate to the ICD-11 classification of
      mental and behavioral disorders. 

PMID- 25388615
TI  - Sural nerve biopsy and functional studies support the pathogenic role of a novel
      MPZ mutation.
AB  - Our patient is a 65-year-old woman presenting with bilateral pes cavus,
      pronounced distal muscle wasting, weakness and areflexia. Electrophysiological
      findings included diffuse unrecordable motor and sensory responses. While the CMT
      phenotype was evident, the lack of family history and the severe, but unspecific
      electrophysiological impairment, was a challenge for genetic diagnosis. A sural
      nerve biopsy was performed, showing a severe loss of myelinated fibers with
      residual axons surrounded by myelin outfoldings. Whereas myelin outfoldings are a
      pathological hallmark of autosomal recessive CMT4B1 and CMT4B2, due to mutations
      in myotubularin-related 2 (MTMR2) and 13 (MTMR13) genes respectively, they may
      also occur in nerve biopsies from CMT1B patients. By direct sequencing, a novel
      heterozygous transversion c.410G>T in MPZ gene was demonstrated, producing an
      amino acid change from glycine to valine in position 108 (p.G108V). In HeLa cells
      the fusion P0G108V-EGFP was normally trafficked to the cell membrane, but with
      decreased P0 adhesion function, compared with wild-type P0, thus supporting a
      pathogenic role of the new variant. In conclusion this case highlights the
      relevance, in selected cases, of sural nerve biopsy to orient the
      genetic/molecular tests, while in vitro analyses may strengthen the pathogenic
      role of novel mutations. 

PMID- 25388616
TI  - Zinc transporter 8 autoantibodies: what is their clinical relevance in
      gestational diabetes?
AB  - AIMS: To investigate the prevalence, clinical significance and antepartum to
      postpartum trajectory of zinc transporter 8 autoantibodies, a novel marker of
      islet autoimmunity, in women with gestational diabetes mellitus. METHODS: A total
      of 302 consecutive women attending a multi-ethnic Australian gestational diabetes
      clinic were prospectively studied. Zinc transporter 8 autoantibodies were
      measured at gestational diabetes diagnosis and 3 months postpartum using an
      enzyme-linked immunosorbent assay, and were correlated with maternal phenotype,
      antepartum and postpartum glucose tolerance, treatment and perinatal outcomes.
      RESULTS: Of the 302 women, 30 (9.9%) were positive for one islet autoantibody
      antepartum. No participant had multiple islet autoantibodies. Zinc transporter 8
      autoantibodies were the most prevalent autoantibody [zinc transporter 8
      autoantibodies: 13/271 women (4.8%); glutamic acid decarboxylase 7/302 women
      (2.3%); insulinoma-associated antigen-2: 6/302 women (2.0%); insulin: 4/302 women
      (1.3%)]. Zinc transporter 8 autoantibody positivity was associated with a higher
      fasting glucose level on the antepartum oral glucose tolerance test, but not with
      BMI, insulin use, perinatal outcomes or postpartum glucose intolerance. Five of
      the six women who tested positive for zinc transporter 8 autoantibodies
      antepartum were negative for zinc transporter 8 autoantibodies postpartum, which
      corresponded to a significant decline in titre antepartum to postpartum (26.5 to
      3.8 U/ml; P=0.03). This was in contrast to the antepartum to postpartum
      trajectory of the other islet autoantibodies, which remained unchanged.
      CONCLUSIONS: Zinc transporter 8 autoantibodies were the most common islet
      autoantibody in gestational diabetes. Zinc transporter 8 autoantibody positivity
      was associated with slightly higher fasting glucose levels and, unlike other
      islet autoantibodies, titres declined postpartum. Zinc transporter 8
      autoantibodies may be a marker for islet autoimmunity in a proportion of women
      with gestational diabetes, but the clinical relevance of zinc transporter 8
      autoantibodies in pregnancy and gestational diabetes requires further
      investigation.

PMID- 25388617
TI  - BCL2 protein signalling determines acute responses to neoadjuvant
      chemoradiotherapy in rectal cancer.
AB  - In locally advanced rectal cancer, neoadjuvant chemoradiotherapy is performed
      prior to surgery to downstage the tumour. Thirty to 40 % of patients do not
      respond. Defects in apoptotic machinery lead to therapy resistance; however, to
      date, no study quantitatively assessed whether B cell lymphoma 2 (BCL2)-dependent
      regulation of mitochondrial apoptosis, effector caspase activation downstream of
      mitochondria or a combination of both predicts patient responses. In a cohort of
      20 rectal cancer patients, we performed protein profiling of tumour tissue and
      employed validated ordinary differential equation-based systems models of
      apoptosis signalling to calculate the ability of cancer cells to undergo
      apoptosis. Model outputs were compared to clinical responses. Systems modelling
      of BCL2-signalling predicted patients in the poor response group (p = 0.0049).
      Systems modelling also demonstrated that rectal cancers depended on BCL2 rather
      than B cell lymphoma-extra large (BCL(X)L) or myeloid cell leukemia 1 (MCL1) for
      survival, suggesting that poor responders may benefit from therapy with selective
      BCL2 antagonists. Dynamic modelling of effector caspase activation could not
      stratify patients with poor response and did not further improve predictive
      power. We deliver a powerful patient stratification tool identifying patients who
      will likely not benefit from neoadjuvant chemoradiotherapy and should be
      prioritised for surgical resection or treatment with BCL2 antagonists. KEY
      MESSAGES: Modelling BCL2-family proteins identifies patients unresponsive to
      therapy. Caspase activation downstream of mitochondria cannot identify these
      patients. Rectal tumours of poor responders are BCL2- but not BCL-XL-dependent.
      DR_MOMP allows clinicians to identify patients who would not benefit from
      therapy. DR_MOMP is also a useful patient stratification tool for BCL2
      antagonists.

PMID- 25388618
TI  - Comparison of a novel chemiluminescence enzyme immunoassay (CLEIA) with enzyme
      linked immunosorbent assay (ELISA) for the determination of MPO-ANCA in patients
      with ANCA-associated vasculitis.
AB  - BACKGROUND: Myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA)
      represents the serological hallmark of ANCA-associated vasculitis (AAV). We
      evaluated the analytical and diagnostic accuracy of chemiluminescence enzyme
      immunoassay (CLEIA) versus enzyme-linked immunosorbent assay (ELISA) for the
      detection of MPO-ANCA. METHODS: A total of 242 sera obtained from 51 patients
      with AAV and 103 patients without AAV were tested for MPO-ANCA by ELISA
      (NephroScholor MPOANC II) and CLEIA (the STACIA MEBLux test). Disease activity in
      the patients with AAV was determined based on the Birmingham Vasculitis Activity
      Score. We analyzed the correlations between the MPO-ANCA titers determined by the
      CLEIA and those determined by the ELISA, and also between the MPO-ANCA titers and
      the disease activity. RESULTS: The MPO-ANCA titers determined by the CLEIA (x)
      were strongly correlated with those determined by the ELISA (y). The correlation
      could be expressed by the following equation in this study: y = 1.8x + 7.7 (r =
      0.96; p < 0.0001). At the cutoff value of 3.5 U/ml, the CLEIA yielded positive
      test results for MPO-ANCA in 73 of the 242 sera (30.2%), while at the cutoff
      value of 20 U/ml, ELISA yielded positive test results in 57 of the 242 sera
      (23.6%). The CLEIA yielded false-positive test results in 4 of the 120 sera
      obtained from the non-AAV patients (3.3%), whereas the ELISA yielded a false
      positive result in only 1 of the 120 sera obtained from the non-AAV patients
      (0.8%). The sensitivity and specificity of the CLEIA for the diagnosis of AAV
      were 100% and 96.7%, respectively, while those of the ELISA were 94.3% and 99.2%,
      respectively. The sensitivity and specificity of the CLEIA for the prediction of
      active disease were 100% and 64.4%, respectively, while those of the ELISA were
      94.3% and 73.6%, respectively. CONCLUSION: The false positivity rate of the CLEIA
      for MPO-ANCA tended to be high as compared with that of the ELISA. Also,
      according to the correlation coefficient between the results of the CLEIA and the
      ELISA calculated in this study, it is necessary to pay attention to the
      differences in the sensitivity and specificity between CLEIA and ELISA.

PMID- 25388619
TI  - Clustered nanocarriers: the effect of size on the clustering of CCMV virus-like
      particles with soft macromolecules.
AB  - Virus-like particles (VLP) could enable a wide variety of biomedical applications
      in therapy, drug delivery, and imaging. They are biocompatible and can be self
      assembled into larger structured materials for additional functionality and
      potentially better biodistribution, which is still a challenging aspect. Here we
      investigate the role of the VLPs size and resulting Caspar Klug symmetry in
      forming clusters out of these building blocks, showing that the onset point for
      clustering is determined by steric considerations of the binding site and binding
      agent. The clustering is independent of cargo and the data suggests that
      rotational symmetry in the T = 3 capsid allows for hexagonal close packed
      structures, whereas the T = 1 capsid that lacks a six-fold and twofold rotational
      axis does not show such organization.

PMID- 25388621
TI  - Co-solvent exfoliation and suspension of hexagonal boron nitride.
AB  - A simple method is presented for exfoliating and suspending hexagonal boron
      nitride using a co-solvent approach. A 60 w/w% concentration of tert-butanol in
      water is very effective at exfoliating boron nitride especially when compared to
      the individual components alone as indicated by UV-vis and transmission electron
      microscopy. Molecular weight and surface tension are found to play inverse roles
      in the exfoliation. 

PMID- 25388620
TI  - Urinary biomonitoring of phosphate flame retardants: levels in California adults
      and recommendations for future studies.
AB  - Phosphate flame retardants (PFRs) are abundant and found at the highest
      concentrations relative to other flame retardant chemicals in house dust;
      however, little is known about the biological levels of PFRs and their
      relationship with house dust concentrations. These relationships provide insight
      into major exposure pathways and potential health risks. We analyzed urine
      samples from 16 California residents in 2011 for 6 chlorinated and nonchlorinated
      dialkyl or diaryl phosphates (DAPs), the expected major metabolites of the most
      prominent PFRs, and qualitatively screened for 18 other metabolites predicted
      from in vitro studies. We detected all 6 DAPs within the range of previously
      reported levels, although very few comparisons are available. We found weakly
      positive nonsignificant correlations between urine and dust concentrations and
      maxima urine corresponding to maxima dust for the pairs bis(1,3-dichloro-2
      propyl) phosphate (BDCIPP)-tris(1,3-dichloro-isopropyl) phosphate (TDCIPP) and
      bis(2-chloroethyl) phosphate (BCEP)-tris(2-chloroethyl) phosphate (TCEP).
      Metabolite levels of PFRs were correlated for many PFR combinations, suggesting
      they commonly co-occur. As far as we know, this is the first study to measure
      these 6 DAP metabolites simultaneously and to detect other PFR metabolites in US
      urine samples. We recommend biomonitoring studies include these 6 DAPs as well as
      several additional compounds detected through qualitative screening and previous
      ADME studies. PFRs represent a class of poorly studied commercial chemicals with
      widespread exposure and raise concerns for health effects including
      carcinogenicity and neurotoxicity.

PMID- 25388622
TI  - The effects of whole grain high-amylose maize flour as a source of resistant
      starch on blood glucose, satiety, and food intake in young men.
AB  - The objective of this study was to determine the dose response effect of whole
      grain high-amylose maize (HAM) flour as a source of resistant starch (RS) on
      blood glucose, appetite and short-term food intake. In a repeated-measures
      crossover trial, healthy men (n = 30, 22.9 +/- 0.6 y, BMI of 22.6 +/- 0.3
      kg/m(2)) were randomly assigned to consume 1 of 3 cookies once a week for 3 wk.
      Cookies were control (100% wheat flour), low-dose (63% wheat flour,37% HAM
      flour), and high-dose (33% wheat flour, 67% HAM flour) providing 53.5, 43.5, and
      36.3 g of available carbohydrate, respectively. Ad libitum food intake was
      measured 120 min at a pizza meal, blood glucose and subjective appetite were
      measured after consumption of the cookie (0 to 120 min) and after the pizza meal
      (140 to 200 min). Blood glucose concentrations were lower at 30 and 45 min after
      high-dose treatment, and at 120 min after both high- and low-dose treatments
      compared to control (P < 0.05). Blood glucose AUC before the pizza meal (0 to 120
      min) was 44% and 14% lower, and higher by 43% and 41% after the pizza meal (140
      to 200 min) compared with control. Yet despite the higher response following the
      meal, cumulative AUC (0 to 200 min) was still 22% lower after the high-dose
      treatment (P < 0.05). All treatments equally suppressed subjective appetite and
      there was no effect on food intake. In conclusion, HAM flour as a source of RS
      and incorporated into a cookie was associated with better glycemic control in
      young men.

PMID- 25388623
TI  - Association between phthalates and externalizing behaviors and cortical thickness
      in children with attention deficit hyperactivity disorder.
AB  - BACKGROUND: Previous studies have implicated the relationship between
      environmental phthalate exposure and attention deficit hyperactivity disorder
      (ADHD) symptoms of childhood, but no studies have been conducted in children who
      have a confirmed diagnosis of ADHD obtained through meticulous diagnostic
      testing. We aimed to determine whether phthalate metabolites in urine would be
      higher in children with ADHD than in those without ADHD and would correlate with
      symptom severity and cortical thickness in ADHD children. METHOD: A cross
      sectional examination of urine phthalate metabolite concentrations was performed;
      scores for ADHD symptoms, externalizing problems, and continuous performance
      tests were obtained from 180 children with ADHD, and brain-imaging data were
      obtained from 115 participants. For the control group, children without ADHD (N =
      438) were recruited. Correlations between phthalate metabolite concentrations and
      clinical measures and brain cortical thickness were investigated. RESULTS:
      Concentrations of phthalate metabolites, particularly the di(2-ethylhexyl)
      phthalate (DEHP) metabolite, were significantly higher in boys with ADHD than in
      boys without ADHD. Concentrations of the di-n-butyl phthalate (DBP) metabolite
      were significantly higher in the combined or hyperactive-impulsive subtypes
      compared to the inattentive subtype, and the metabolite was positively correlated
      with the severity of externalizing symptoms. Concentrations of the DEHP
      metabolite were negatively correlated with cortical thickness in the right middle
      and superior temporal gyri. CONCLUSIONS: The results of this study suggest an
      association between phthalate concentrations and both the diagnosis and symptom
      severity of ADHD. Imaging findings suggest a negative impact of phthalates on
      regional cortical maturation in children with ADHD.

PMID- 25388624
TI  - The laboratory performance of the enFLOW((r)) , buddy lite(TM) and
      ThermoSens((r)) fluid warmers.
AB  - We measured heating of isotonic saline by three fluid warmers in six experiments:
      saline at 5  degrees C or 20  degrees C delivered at 30, 50 or 100 ml.min(-1) .
      At the three flow rates, the enFLOW((r)) , buddy lite(TM) and ThermoSens((r))
      systems heated 5  degrees C saline to mean (SD) temperatures of: 41.1 (0.5) 
      degrees C, 37.7 (0.6)  degrees C and 39.1 (0.6)  degrees C; to 40.3 (0.8) 
      degrees C, 33.9 (1.6)  degrees C and 39.3 (0.7)  degrees C; and to 37.1 (0.8) 
      degrees C, 24.0 (1.3)  degrees C and 37.6 (1.0)  degrees C, respectively, p <
      0.0001 for each experiment. The mean (SD) times taken to heat 5  degrees C saline
      were: 16.6 (1.7) s, 258.4 (58.9) s and 134.2 (79.6) s; 16.9 (1.8) s, 256.2 (62.2)
      s and 182.5 (74.5) s; and 21.5 (1.5) s, 275.9 (49.3) s and 313.5 (18.0) s,
      respectively, p < 0.0003 for each experiment. The results for saline at 20 
      degrees C were similar. The enFLOW system heated saline above 36  degrees C
      faster than the ThermoSens system, whereas the buddy lite often failed to achieve
      36  degrees C.

PMID- 25388626
TI  - Solid fuel in kitchen and acute respiratory tract infection among under five
      children: evidence from Nepal demographic and health survey 2011.
AB  - This study assessed the association between use of solid fuel in kitchen and ARI
      among under five children in Nepal. The latest data from the Nepal Demographic
      and Health Survey 2011 were used. A total of 4,802 under 5 de-jure children were
      included in this analysis. Cough accompanied by short/rapid breath and chest
      problem within 2 weeks before survey was considered as the symptoms of ARI.
      Logistic regression analysis was performed to calculate the odds of being
      suffered from ARI among the children from households using solid fuel in
      comparison to the children from households using cleaner fuel. About 84.6% of the
      families used solid fuel as a primary fuel. Approximately 4.5% children had
      symptoms of ARI within 2 weeks before the survey. About 3.4 and 4.9% of children
      from the families using cleaner fuel and solid fuel respectively had symptoms of
      ARI within 2 weeks preceding survey. After adjusting for age, sex, birth order,
      urban/rural residence, ecological zone, development region, economic status,
      number of family members, mother's smoking status and mother's education, odds of
      suffering from ARI was 1.79 times higher among the children from the households
      using solid fuel in comparison to the children from households using cleaner fuel
      (95% CI 1.02, 3.14). This study found the use of solid fuel in the kitchen has as
      a risk factor for ARI among under five children in Nepal. Longitudinal studies
      with direct measurement of indoor air pollution and clinical ARI cases can be
      future research priority.

PMID- 25388625
TI  - Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus
      contortus.
AB  - BACKGROUND: Phosphoinositide 3-kinases (PI3Ks) are relatively conserved and
      important intracellular lipid kinases involved in signalling and other biological
      pathways. In the free-living nematode Caenorhabditis elegans, the heterodimeric
      form of PI3K consists of catalytic (AGE-1) and regulatory (AAP-1) subunits. These
      subunits are key components of the insulin-like signalling pathway and play roles
      in the regulation of the entry into and exit from dauer. Although, in parasitic
      nematodes, similar components are proposed to regulate the transition from free
      living or arrested stages to parasitic larvae, nothing is known about PI3Ks in
      relation to the transition of third-stage larvae (L3s) to parasitism in
      Haemonchus contortus. METHODS: An integrated molecular approach was used to
      investigate age-1 and aap-1 of H. contortus (Hc-age-1 and Hc-aap-1) in C.
      elegans. RESULTS: The two genes Hc-age-1 and Hc-aap-1 were transcribed in all
      life stages, with the highest levels in the egg, infective L3 and adult female of
      H. contortus. The expression of these genes was localized to the intestine,
      contrasting the pattern of their orthologues in C. elegans (where they are
      expressed in both head neurons and the intestine). The yeast two-hybrid analysis
      demonstrated that the adaptor-binding domain of Hc-AGE-1 interacted strongly with
      the Hc-AAP-1; however, this complex did not rescue the function of its orthologue
      in age-1-deficient C. elegans. CONCLUSIONS: This is the first time that the PI3K
      encoding genes have been characterized from a strongylid parasitic nematode. The
      findings provide insights into the role of the PI3K heterodimer represented by Hc
      age-1 and Hc-aap-1 in the developmental biology of H. contortus.

PMID- 25388627
TI  - Public bike sharing in New York City: helmet use behavior patterns at 25 Citi
      BikeTM stations.
AB  - Urban public bicycle sharing programs are on the rise in the United States.
      Launched in 2013, NYC's public bicycle share program, Citi BikeTM is the fastest
      growing program of its kind in the nation, with nearly 100,000 members and more
      than 330 docking stations across Manhattan and Brooklyn. The purpose of this
      study was to assess helmet use behavior among Citi BikeTM riders at 25 of the
      busiest docking stations. The 25 Citi BikeTM Stations varied greatly in terms of
      usage: total number of cyclists (N = 96-342), commute versus recreation (22.9
      79.5% commute time riders), weekday versus weekend (6.0-49.0% weekend riders).
      Helmet use ranged between 2.9 and 29.2% across sites (median = 7.5 %). A total of
      4,919 cyclists were observed, of whom 545 (11.1%) were wearing helmets. Incoming
      cyclists were more likely to wear helmets than outgoing cyclists (11.0 vs 5.9%, p
      = .000). NYC's bike share program endorses helmet use, but relies on education to
      encourage it. Our data confirm that, to date, this strategy has not been
      successful.

PMID- 25388628
TI  - Barley beta-glucan promotes MnSOD expression and enhances angiogenesis under
      oxidative microenvironment.
AB  - Manganese superoxide dismutase (MnSOD), a foremost antioxidant enzyme, plays a
      key role in angiogenesis. Barley-derived (1.3) beta-d-glucan (beta-d-glucan) is a
      natural water-soluble polysaccharide with antioxidant properties. To explore the
      effects of beta-d-glucan on MnSOD-related angiogenesis under oxidative stress, we
      tested epigenetic mechanisms underlying modulation of MnSOD level in human
      umbilical vein endothelial cells (HUVECs) and angiogenesis in vitro and in vivo.
      Long-term treatment of HUVECs with 3% w/v beta-d-glucan significantly increased
      the level of MnSOD by 200% +/- 2% compared to control and by 50% +/- 4% compared
      to untreated H2 O2 -stressed cells. beta-d-glucan-treated HUVECs displayed
      greater angiogenic ability. In vivo, 24 hrs-treatment with 3% w/v beta-d-glucan
      rescued vasculogenesis in Tg (kdrl: EGFP) s843Tg zebrafish embryos exposed to
      oxidative microenvironment. HUVECs overexpressing MnSOD demonstrated an increased
      activity of endothelial nitric oxide synthase (eNOS), reduced load of superoxide
      anion (O2 (-) ) and an increased survival under oxidative stress. In addition,
      beta-d-glucan prevented the rise of hypoxia inducible factor (HIF)1-alpha under
      oxidative stress. The level of histone H4 acetylation was significantly increased
      by beta-d-glucan. Increasing histone acetylation by sodium butyrate, an inhibitor
      of class I histone deacetylases (HDACs I), did not activate MnSOD-related
      angiogenesis and did not impair beta-d-glucan effects. In conclusion, 3% w/v beta
      d-glucan activates endothelial expression of MnSOD independent of histone
      acetylation level, thereby leading to adequate removal of O2 (-) , cell survival
      and angiogenic response to oxidative stress. The identification of dietary beta-d
      glucan as activator of MnSOD-related angiogenesis might lead to the development
      of nutritional approaches for the prevention of ischemic remodelling and heart
      failure.

PMID- 25388629
TI  - Ratio between fms-like tyrosine kinase 1 and placental growth factor in children
      with congenital heart disease.
AB  - Serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), an antiangiogenic
      factor, and its binding protein, placental growth factor (PlGF), are altered in
      women with preeclampsia. Recently, the sFlt-1/PlGF ratio has been shown to
      predict acute coronary syndrome in adults. However, few reports have described
      the use of the sFlt-1/PlGF ratio for evaluating an abnormal hemodynamic load in
      children with congenital heart disease (CHD). The sFlt-1/PlGF ratio was
      determined in 20 children with atrial septal defects (ASD), 26 children with
      ventricular septal defects (VSD), 57 children with tetralogy of Fallot (ToF), 35
      children who were Fontan candidates (Fontan), and 14 controls. The preoperative
      sFlt-1/PlGF ratios in the ASD, VSD, and Fontan were significantly higher than
      those in the controls and were significantly decreased after surgical repair in
      the ASD and VSD. In the ToF, the sFlt-1/PlGF ratio was highest after first-stage
      repair and second-highest after final-stage palliation compared with the
      preoperative levels. The sFlt-1/PlGF ratio was highest after first-stage repair
      and much lower after final-stage palliation in the Fontan. Furthermore, these
      ratios correlated with the degree of the ventricular volume overload and hypoxia.
      Our study clearly demonstrated that the sFlt-1/PlGF ratio increases with volume
      overload and persistent hypoxia after surgery with CHD. These findings may prove
      useful in the management of CHD in children. 

PMID- 25388630
TI  - Balloon dilation and surgical valvotomy comparison in non-critical congenital
      aortic valve stenosis.
AB  - Percutaneous balloon aortic valvoplasty (BAV) and surgical aortic valvotomy (SAV)
      are palliative procedures in patients with non-critical congenital valve
      stenosis. The aim of the study was to evaluate long-term BAV and SAV results
      after up to 24 years of follow-up. From 1987 to 2013, 74 consecutive
      interventions were performed in patients with aortic stenosis, and 62 were
      included in the study (39 BAVs and 23 SAVs). Age of BAV patients was 1.3 months
      to 17 years, and of SAV patients 1.2 months to 15 years. Although BAV patients
      were older, there was no difference between groups according to sex, valve
      function/morphology, and early/late follow-up results, with exception to
      hospitalization period. Significant pressure gradient reduction and aortic
      regurgitation increment were registered after procedures. Three patients did not
      survive early period after surgery. Follow-up period was 7.0 +/- 5.4 and 9.0 +/-
      8.0 years after BAV and SAV, respectively (p = 0.242). Follow-up pressure
      gradient rose only in the BAV group, and was emphasized after 10-year-follow-up
      (p = 0.020). Significant aortic insufficiency progression was registered after 15
      years of follow-up in both groups (p = 0.007 and p = 0.009, respectively). Mean
      reintervention-free survival was 12.0 years in the BAV and 14.5 years in the SAV
      group (p = 0.733), and mean survival without aortic valve replacement was 15.2
      and 17.4 years, respectively (p = 0.877). BAV and SAV in patients with congenital
      aortic stenosis are very comparable in both early and late follow-up results. 

PMID- 25388631
TI  - Bias related to body mass index in pediatric echocardiographic Z scores.
AB  - In pediatric echocardiography, cardiac dimensions are often normalized for
      weight, height, or body surface area (BSA). The combined influence of height and
      weight on cardiac size is complex and likely varies with age. We hypothesized
      that increasing weight for height, as represented by body mass index (BMI)
      adjusted for age, is poorly accounted for in Z scores normalized for weight,
      height, or BSA. We aimed to evaluate whether a bias related to BMI was introduced
      when proximal aorta diameter Z scores are derived from bivariate models (only one
      normalizing variable), and whether such a bias was reduced when multivariable
      models are used. We analyzed 1,422 echocardiograms read as normal in children
      <=18 years. We computed Z scores of the proximal aorta using allometric,
      polynomial, and multivariable models with four body size variables. We then
      assessed the level of residual association of Z scores and BMI adjusted for age
      and sex. In children >=6 years, we found a significant residual linear
      association with BMI-for-age and Z scores for most regression models. Only a
      multivariable model including weight and height as independent predictors
      produced a Z score free of linear association with BMI. We concluded that a bias
      related to BMI was present in Z scores of proximal aorta diameter when
      normalization was done using bivariate models, regardless of the regression model
      or the normalizing variable. The use of multivariable models with weight and
      height as independent predictors should be explored to reduce this potential
      pitfall when pediatric echocardiography reference values are evaluated. 

PMID- 25388632
TI  - Successful treatment of tufted angioma with propranolol.

PMID- 25388633
TI  - Preoperative deltoid size and fatty infiltration of the deltoid and rotator cuff
      correlate to outcomes after reverse total shoulder arthroplasty.
AB  - BACKGROUND: Reverse total shoulder arthroplasty (RTSA) allows the deltoid to
      substitute for the nonfunctioning rotator cuff. To date, it is unknown whether
      preoperative deltoid and rotator cuff parameters correlate with clinical
      outcomes. QUESTIONS/PURPOSES: We asked whether associations exist between 2-year
      postoperative results (ROM, strength, and outcomes scores) and preoperative (1)
      deltoid size; (2) fatty infiltration of the deltoid; and/or (3) fatty
      infiltration of the rotator cuff. METHODS: A prospective RTSA registry was
      reviewed for patients with cuff tear arthropathy or massive rotator cuff tears,
      minimum 2-year followup, and preoperative shoulder MRI. Final analysis included
      30 patients (average age, 71+/-10 years; eight males, 22 females). Only a small
      proportion of patients who received an RTSA at our center met inclusion and
      minimum followup requirements (30 of 222; 14%); however, these patients were
      found to be similar at baseline to the overall group of patients who underwent
      surgery in terms of age, gender, and preoperative outcomes scores. The cross
      sectional area of the anterior, middle, and posterior deltoid was measured on
      axial proton density-weighted MRI. Fatty infiltration of the deltoid,
      supraspinatus, infraspinatus, teres minor, and subscapularis were quantitatively
      assessed on sagittal T1-weighted MR images. Patients were followed for Constant
      Murley score, American Shoulder and Elbow Surgeons (ASES) scores, subjective
      shoulder value, pain, ROM, and strength. Correlations of muscle parameters with
      all outcomes measures were calculated. RESULTS: Preoperative deltoid size
      correlated positively with postoperative Constant-Murley score (67.27+/-13.07)
      (rho=0.432, p=0.017), ASES (82.64+/-14.25) (rho=0.377; p=0.40), subjective
      shoulder value (82.67+/-17.89) (rho=0.427; p=0.019), and strength (3.72 pounds+/
      2.99 pounds) (rho=0.454; p=0.015). Quantitative deltoid fatty infiltration
      (7.91%+/-4.32%) correlated with decreased postoperative ASES scores (rho=-0.401;
      p=0.047). Quantitative fatty infiltration of the infraspinatus (30.47%+/-15.01%)
      correlated with decreased postoperative external rotation (34.13 degrees +/-16.80
      degrees ) (rho=-0.494; p=0.037). CONCLUSIONS: Larger preoperative deltoid size
      correlates with improved validated outcomes scores, whereas fatty infiltration of
      the deltoid and infraspinatus may have deleterious effects on validated outcomes
      scores and ROM after RTSA. The current study is a preliminary exploration of this
      topic; future studies should include prospective enrollment and standardized MRI
      with a multivariate statistical approach. Quantitative information attained from
      preoperative imaging not only holds diagnostic value, but, should future studies
      confirm our findings, also might provide prognostic value. This information may
      prove beneficial in preoperative patient counseling and might aid preoperative
      and postoperative decision-making by identifying subpopulations of patients who
      may benefit by therapy aimed at improving muscle properties. LEVEL OF EVIDENCE:
      Level III, prognostic study.

PMID- 25388634
TI  - CORR Insights (r): Can femoral rotation be localized and quantified using
      standard CT measures?

PMID- 25388635
TI  - New therapeutic approach by G2013 in experimental model of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system
      (CNS) that leads to an inflammatory demyelination and axonal damage. MS disease
      often displays a relapsing-remitting course of neurological manifestations that
      is mimicked by experimental autoimmune encephalomyelitis (EAE) in animal models.
      The aim of the present research was to test the therapeutic effect of small
      molecule G2013, a novel designed non-steroidal anti-inflammatory agent in EAE.
      All experiments were conducted on C57BL/6 male mice aged 10 weeks. To induce the
      EAE, we performed subcutaneously injection of myelin oligodendrocyte glycoprotein
      35-55 (MOG35-55) in Complete Freund's Adjuvant (CFA) emulsion, and for treatment
      of EAE we used intraperitoneal (IP) injection of G2013. On day 21 post
      immunization, for total antioxidant, nitric oxide (NO) and TNF-alpha assessment,
      blood samples were taken from the heart and mice were killed, and the brains and
      cerebellums were then removed for histological analysis. Our findings
      demonstrated that G2013 had beneficial effects on EAE by lower incidence,
      attenuation in the severity, and a delay in the onset of disease. Histological
      analysis showed that inflammation criteria including the number of inflammatory
      cells and plaques as well as demyelination in G2013 dosed mice were lower than
      control group. Moreover, the serum level of NO in G2013-treated mice was
      significantly less than control animals. These data indicate that G2013 therapy
      can attenuate the disease progression in experimental model of MS.

PMID- 25388636
TI  - Bacterial effector modulation of host E3 ligase activity suppresses PAMP
      triggered immunity in rice.
AB  - Pathogen effector proteins are delivered to host cells to suppress plant
      immunity. However, the mechanisms by which effector proteins function are largely
      unknown. Here we show that expression of XopP(Xoo), an effector of rice pathogen
      Xanthomonas oryzae pv. oryzae, in rice strongly suppresses peptidoglycan (PGN)-
      and chitin-triggered immunity and resistance to X. oryzae. XopP(Xoo) targets
      OsPUB44, a rice ubiquitin E3 ligase with a unique U-box domain. We find that
      XopP(Xoo) directly interacts with the OsPUB44 U-box domain and inhibits ligase
      activity. Two amino-acid residues specific for the OsPUB44 U-box domain are
      identified, which are responsible for the interaction with XopP(Xoo). Silencing
      of OsPUB44 suppresses PGN- and chitin-triggered immunity and X. oryzae
      resistance, indicating that OsPUB44 positively regulates immune responses. Thus,
      it is likely that XopP(Xoo) suppresses immune responses by directly interacting
      with and inhibiting a positive regulator of plant immunity.

PMID- 25388637
TI  - Impact of brief and sequential exposure to nystatin, amphotericin B,
      ketoconazole, and fluconazole in modulating adhesion traits of oral Candida
      dubliniensis isolates.
AB  - AIM: Candida adherence is implicated in the pathogenesis of oral candidosis.
      Adhesion to buccal epithelial cells (BEC), germ tube (GT) formation, and relative
      cell surface hydrophobicity (CSH) are colonization attributes of candidal
      pathogenicity. Candida dubliniensis (C. dubliniensis) is allied with recurrent
      oral candidosis, which can be treated with nystatin, amphotericin B,
      ketoconazole, and fluconazole. Due to the diluent effect of saliva and the
      cleansing effect of the oral musculature in the oral cavity C. dubliniensis
      isolates undergo brief and sequential exposure to antifungal agents during
      therapy. Thus, in the present study, we evaluated the adhesion to BEC, GT
      formation, and the CSH of oral isolates of C. dubliniensis following brief and
      sequential exposure to nystatin, amphotericin B, ketoconazole, and fluconazole.
      METHODS: After determining the minimum inhibitory concentration (MIC) of the
      aforementioned drugs, 20 oral isolates of C. dubliniensis were briefly (1 h), and
      sequentially (10 days) exposed to subcidal concentrations of these drugs.
      Following drug removal, adhesion to BEC, GT formation, and CSH of these isolates
      were determined. RESULTS: The percentage reduction of adhesion to BEC, GT
      formation, and CSH of the isolates following exposure to antifungal agents were
      as follows: nystatin: 53.55%, 33.98%, and 29.83% (P < 0.001); amphotericin B:
      53.84%, 36.23%, and 28.97% (P < 0.001); ketoconazole: 37.43%, 20.51%, and 16.49%
      (P < 0.001); and fluconazole: 8.93% (P < 0.001), 1.6%, and 0.63% (P > 0.05).
      CONCLUSIONS: Brief and sequential exposure of C. dubliniensis to antifungal
      agents would continue to wield an antifungal effect by altering its adhesion
      attributes, and elucidate possible pharmacodynamics by which antifungal agents
      might operate in modulating candidal adherence.

PMID- 25388638
TI  - Consequences of stratospheric ozone depletion and climate change on the use of
      materials.
AB  - Materials used in the exterior of buildings and in construction are routinely
      exposed to solar UV radiation. Especially in the case of wood and plastic
      building materials, the service life is determined by their weather-induced
      deterioration. Any further increase in ground-level solar UV radiation, UV-B
      radiation in particular, will therefore reduce the outdoor service life of these
      products. Any increase in ambient temperature due to climate change will also
      have the same effect. However, the existing light-stabilizer technologies are
      likely to be able to mitigate the additional damaging effects due to increased
      solar UV radiation and maintain the outdoor lifetimes of these materials at the
      present levels. These mitigation choices invariably increase the lifetime cost of
      these products. A reliable estimate of what this additional cost might be for
      different products is not available at the present time. Personal exposure to UV
      radiation is reduced both by clothing fabrics and glass windows used in buildings
      and automobiles. This assessment describes how the recent technical advances in
      degradation and stabilization techniques impact the lifetimes of plastics and
      wood products routinely exposed to solar UV radiation and the protection to
      humans offered by materials against solar UV radiation. 

PMID- 25388639
TI  - Electrostatic analysis of bacterial expansins.
AB  - Expansins are a family of proteins with plant cell wall remodeling-activity,
      which bind cell wall components through hydrophobic and electrostatic
      interactions. A shallow area on the surface of the protein serves as the
      polysaccharide binding site (PBS) and it is composed of conserved residues.
      However, electric charge differences on the opposite face of the PBS produce
      basic, neutral, or acidic proteins. An analysis of forty-four bacterial
      expansins, homologues of BsEXLX1, revealed two main groups defined by: (a) the
      presence or absence of disulfide bonds; and (b) by the proteins isoelectric point
      (pI). We determined the location of the residues responsible for the pI on the
      structure of representative expansins. Our results suggest that the electric
      charge at the opposite site of the PBS may help in substrate differentiation
      among expansins from different species; in addition, electrostatic polarization
      between the front and the back of the molecule could affect expansin activity on
      cellulose.

PMID- 25388640
TI  - SNP discovery in nonmodel organisms: strand bias and base-substitution errors
      reduce conversion rates.
AB  - Single nucleotide polymorphisms (SNPs) have become the marker of choice for
      genetic studies in organisms of conservation, commercial or biological interest.
      Most SNP discovery projects in nonmodel organisms apply a strategy for
      identifying putative SNPs based on filtering rules that account for random
      sequencing errors. Here, we analyse data used to develop 4723 novel SNPs for the
      commercially important deep-sea fish, orange roughy (Hoplostethus atlanticus), to
      assess the impact of not accounting for systematic sequencing errors when
      filtering identified polymorphisms when discovering SNPs. We used SAMtools to
      identify polymorphisms in a velvet assembly of genomic DNA sequence data from
      seven individuals. The resulting set of polymorphisms were filtered to minimize
      'bycatch'-polymorphisms caused by sequencing or assembly error. An Illumina
      Infinium SNP chip was used to genotype a final set of 7714 polymorphisms across
      1734 individuals. Five predictors were examined for their effect on the
      probability of obtaining an assayable SNP: depth of coverage, number of reads
      that support a variant, polymorphism type (e.g. A/C), strand-bias and Illumina
      SNP probe design score. Our results indicate that filtering out systematic
      sequencing errors could substantially improve the efficiency of SNP discovery. We
      show that BLASTX can be used as an efficient tool to identify single-copy genomic
      regions in the absence of a reference genome. The results have implications for
      research aiming to identify assayable SNPs and build SNP genotyping assays for
      nonmodel organisms. 

PMID- 25388641
TI  - Specific N-terminal cleavage of ribosomal protein L27 in Staphylococcus aureus
      and related bacteria.
AB  - Ribosomal protein L27 is a component of the eubacterial large ribosomal subunit
      that has been shown to play a critical role in substrate stabilization during
      protein synthesis. This function is mediated by the L27 N-terminus, which
      protrudes into the peptidyl transferase center. In this report, we demonstrate
      that L27 in Staphylococcus aureus and other Firmicutes is encoded with an N
      terminal extension that is not present in most Gram-negative organisms and is
      absent from mature ribosomes. We have identified a cysteine protease, conserved
      among bacteria containing the L27 N-terminal extension, which performs post
      translational cleavage of L27. Ribosomal biology in eubacteria has largely been
      studied in the Gram-negative bacterium Escherichia coli; our findings indicate
      that there are aspects of the basic biology of the ribosome in S. aureus and
      other related bacteria that differ substantially from that of the E. coli
      ribosome. This research lays the foundation for the development of new
      therapeutic approaches that target this novel pathway.

PMID- 25388642
TI  - Phosphorylation of AKT(Ser473) serves as an independent prognostic marker for
      radiosensitivity in advanced head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by high
      resistance to radiotherapy, which critically depends on both altered signaling
      pathways within tumor cells and their dynamic interaction with the tumor
      microenvironment. This study evaluated the prognostic value of the
      phosphorylation status of AKT on Ser473 and Thr308 for the clinical outcome of
      patients with advanced HNSCC on radiotherapy. Furthermore, we investigated the
      impact of AKT(Ser473) phosphorylation [p-AKT(Ser473)] in the context of
      radioresistance using ex vivo tissue cultures that resemble the complex tissue
      architecture and paracrine interaction with the tumor microenvironment. In a
      cohort of 120 patients with advanced HNSCC, who were treated with primary or
      adjuvant radiotherapy, a significant association was found between relative p
      AKT(Ser473) levels and overall survival (p = 0.006) as well as progression-free
      survival (p = 0.021), while no significant correlation was revealed for relative
      p-AKT(Thr308) levels. In ex vivo tissue cultures p-AKT(Ser473) levels were
      increased upon irradiation and treatment with the PI3K inhibitor LY294002
      inhibited both basal and irradiation induced AKT(Ser473) phosphorylation.
      Strikingly, pretreatment with LY294002 sensitized tissue cultures derived from
      primary and recurrent tumors to radiotherapy as determined by impaired tumor cell
      proliferation and enhanced DNA damage. In conclusion, phosphorylation status of
      AKT(Ser473) in tumor specimens serves as a novel biomarker to identify patients
      with advanced HNSCC at high risk for treatment failure following radiotherapy,
      and our data from ex vivo tissue cultures support the assumption that
      pharmacological inhibition of AKT(Ser473) phosphorylation might circumvent
      radioresistance to improve efficiency and reduce toxicity of current treatment
      modalities.

PMID- 25388643
TI  - Hyaluronic acid and glucosamine sulfate for adult Kashin-Beck disease: a cluster
      randomized, placebo-controlled study.
AB  - To evaluate the efficacy and safety of hyaluronic acid (HA) and glucosamine
      sulfate (GS) in alleviating symptoms and improving function of Kashin-Beck
      disease (KBD). A cluster-randomized, placebo-controlled trial was conducted in
      150 patients with KBD. Participants were randomly allocated to receive intra
      articular injection hyaluronic acid (IAHA) for 4 weeks, oral GS for 12 weeks, or
      oral placebo for 12 weeks. The primary outcome measures were 20 % and 50 %
      reductions in pain from baseline measured by the Western Ontario and McMaster
      Universities Osteoarthritis (WOMAC) index. Secondary outcome measures included
      WOMAC index parameters of pain, stiffness, and physical function. The third
      outcome measure was mean change in Lequence score. HA and GS were effective in
      reducing WOMAC pain by 20 % (differences of 43.5 % and 25.4 %) and 50 %
      (differences of 43.4 % and 26.9 %). Both HA and GS significantly reduced WOMAC
      pain, WOMAC stiffness, and WOMAC normalized score compared with placebo group
      (all P < 0.05). IAHA was significantly more effective than oral GS in improving
      WOMAC normalized score (P = 0.034), pain (P = 0.002), stiffness (P = 0.018), and
      function (P = 0.044). The results indicate that HA and GS were more effective
      than placebo in treating KBD and HA was more effective than GS. 

PMID- 25388644
TI  - Rituximab use in patients with ANCA-associated vasculitis: clinical efficacy and
      impact on immunological parameters.
AB  - Rituximab (RTX) was reported effective in ANCA-associated vasculitis (AAV). We
      aimed to evaluate clinical efficacy of RTX in AAV along with its impact on
      immunological parameters. Eighteen RTX-treated AAV patients (M/F 11/7; median age
      37.5; 15* PR3-ANCA, 3* MPO-ANCA; 16* relapsing/refractory, 2* first-line therapy)
      were enrolled. Clinical response, ANCA, total serum IgG levels and cellular
      immunity parameters were examined. The patients were followed up (FU) for a
      median of 26 months (range 3-82, 15 for >=6 months). All patients achieved B cell
      depletion (lasting 3-24 months). No significant increase was noted in T cell or
      NK cell subpopulations. At 6 months, partial remission was achieved in 5/15
      patients (33 %) and complete in 8 (53 %). The median prednisone dose (30..10
      mg/d) and ANCA levels (17.2..2.7 IU/mL) decreased (p < 0.01). RTX retreatment was
      used in nine (8* pre-emptive, 1* relapse). Six patients relapsed (none of the pre
      emptively treated). Three patients died of infection. IgG levels at 3 months
      decreased compared to baseline (9.0 vs 5.7 g/L, p < 0.01). Higher percentage of
      HLA-DR+CD3+ cells and lower percentage of CD4+CD45RA+ naive T cells persisted
      during FU. IFN-gamma production increased at 6 months compared to baseline (27.3
      vs 41.5 %). No significant change was noted in the intracellular IL-10 and IL-12
      production. RTX helped to lower the glucocorticosteroids dose and withdraw
      cytotoxic drugs in most AAV patients. Hypogammaglobulinaemia was common but well
      tolerated. Peripheral circulating T cells remained activated despite B cell
      depletion. 

PMID- 25388645
TI  - Association of abnormal lipid spectrum with the disease activity of Takayasu
      arteritis.
AB  - Our study aimed to determine whether proatherogenic lipid profiles exist in
      patients with active Takayasu arteritis (TA) and assess the relationship between
      different lipid profiles and disease activity in TA. A total of 132 premenopausal
      female patients with TA and 100 sex-, age-, and body mass index-matched healthy
      controls were included in our study. The clinical data were collected in detail
      from all participants. Patients with active TA had significantly lower levels of
      apolipoprotein A1 (apoA1) (1.47 +/- 0.30 vs. 1.99 +/- 0.33 mmol/L, p < 0.001) and
      lower levels of high-density lipoprotein cholesterol (HDL-C) (1.23 +/- 0.33 vs.
      1.68 +/- 0.38 mmol/L, p < 0.001) than patients with inactive TA. However, they
      had higher ratios of apolipoprotein B (apoB)/apoA1 (0.74 +/- 0.27 vs. 0.48 +/-
      0.14, p < 0.001) compared with patients with inactive TA. Multiple linear
      regression analysis demonstrated that the apoB/apoA1 ratio was independently
      associated with TA activity (beta = 0.38, p = 0.04). In addition, multivariate
      stepwise forward regression analysis showed that the apoB/apoA1 ratio was the
      major determinant for high-sensitivity C-reactive protein (beta = 0.58, p =
      0.002). Our findings indicate that patients with active TA had proatherogenic
      lipid profiles. In addition, the ratio of apoB to apoA1 could be used as a marker
      for monitoring and targeting patients with TA.

PMID- 25388646
TI  - Physical impairment in patients with idiopathic inflammatory myopathies is
      associated with the American College of Rheumatology functional status measure.
AB  - The goals of this study were to assess the predictive value of chart-abstracted
      American College of Rheumatology functional status (ACR-FS) with patient-reported
      ACR-FS and to relate it with measures of muscle function in a single-institution
      cohort of patients with idiopathic inflammatory myopathies (IIMs). Demographic
      and clinical data of 102 patients with IIMs regularly followed in the
      Rheumatology and Neurology Clinics at the University of Kentucky Medical Center
      between 2006 and 2012 were obtained through retrospective chart review. Clinical
      and functional status evaluation, muscle performance testing, and body
      composition measures were performed on a subset of 21 patients. ACR-FS was
      obtained by both chart abstraction and direct patient report. Spearman's
      correlations were used to examine the relationship of ACR-FS derived from chart
      abstraction with direct patient report, as well as the relationship of measures
      of physical function and body composition with ACR-FS. ACR-FS derived from chart
      abstraction was significantly correlated with ACR-FS derived from direct patient
      report (rho = 0.78, p < 0.001). ACR-FS derived from chart abstraction was also
      significantly correlated with patient-reported physical function (rho = -0.71, p
      < 0.001) and physical activity (rho = -0.58, p < 0.05), manual muscle testing
      (rho = -0.66, p < 0.01), and skeletal muscle endurance as measured by the
      functional index-2 test (shoulder flexion rho = -0.62, p < 0.01; hip flexion rho
      = -0.65, p < 0.0; heel lift rho = -0.67, p < 0.01; and toe lift rho = -0.68, p <
      0.01). The ACR-FS is a simple measure of disability that can be used in chart
      abstraction studies involving IIM patients. We have demonstrated that ACR-FS
      correlates well with muscle performance tests of strength and endurance.

PMID- 25388647
TI  - Meeting the Transition Needs of Urban American Indian/Alaska Native Youth through
      Culturally Based Services.
AB  - This article reports findings from three qualitative studies exploring supports
      for positive transitions of American Indian/Alaska Native (AI/AN) youth to
      adulthood. Community-based participatory methods were employed through a research
      partnership involving a culturally based community agency, the Native American
      Youth and Family Center (NAYA), the National Indian Child Welfare Association,
      and Portland State University. Studies utilized a Relational Worldview (RWV)
      framework, where well-being is understood as a balance among the domains of mind,
      body, spirit, and context. Collectively, findings demonstrate that NAYA employs
      culturally grounded interventions to overcome the traumatic histories and current
      oppressive conditions affecting low-income urban AI/AN youth with mental health
      challenges and to support their well-being and transition to adulthood. In
      addition, addressing the mental health and well-being of AI/AN youth in
      culturally appropriate ways involves consideration of all RWV domains.
      Recommendations for behavioral health practice are to connect AI/AN youth to
      culturally specific services whenever possible, utilize cultural consultants, and
      implement holistic and positive approaches to mental health. 

PMID- 25388648
TI  - Treatment of multiple myeloma bone disease: experimental and clinical data.
AB  - INTRODUCTION: Bone disease is present in the majority of patients with multiple
      myeloma and can seriously affect quality of life and survival rate. In addition
      to suppression of osteoclastogenesis, there have been developments made in terms
      of the therapeutic agents available, such as novel immunomodulating agents,
      proteasome and receptor activator of nuclear factor kappaB ligand inhibitors.
      AREAS COVERED: AREAS COVERED include in vitro, in vivo and clinical evidence was
      collected using MEDLINE (1950 - May 2014), EMBASE (1980 - May 2014) and Google
      Scholar (1980 - May 2014) databases. EXPERT OPINION: Bisphosphonates are the
      mainstay of myeloma bone disease treatment. Oral clodronate and intravenous
      pamidronate and zoledronic acid are currently used drugs and seem to have
      comparable results in preventing skeletal-related events of the disease.
      Zoledronate can also have survival benefits and based on the available evidence
      is the superior bisphosphonate; however, its side effects have to be monitored.
      Denosumab had comparable results with zoledronate on myeloma bone disease
      treatment; its use has not been completely proven yet. There is an expanding set
      of drugs, proteasome inhibitors, under investigation with great potential to
      reduce the negative effects of myeloma cells on bone. Future clinical studies
      should compare both the catabolic and anabolic effects of these agents on bone.

PMID- 25388649
TI  - Superoxide anion production and expression of gp91(phox) and p47(phox) are
      increased in glomeruli and proximal tubules of cisplatin-treated rats.
AB  - The chemotherapeutic drug cisplatin has some side effects including
      nephrotoxicity that has been associated with reactive oxygen species production,
      particularly superoxide anion. The major source of superoxide anion is
      nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase. However,
      the specific segment of the nephron in which superoxide anion is produced has not
      been identified. Rats were sacrificed 72 h after cisplatin injection (7.5 mg/kg),
      and kidneys were obtained to isolate glomeruli and proximal and distal tubules.
      Cisplatin induced superoxide anion production in glomeruli and proximal tubules
      but not in distal tubules. This enhanced superoxide anion production was
      prevented by diphenylene iodonium, an inhibitor of NADPH oxidase. Consistently,
      this effect was associated with the increased expression of gp91(phox) and
      p47(phox), subunits of NADPH oxidase. The enhanced superoxide anion production in
      glomeruli and proximal tubules, associated with the increased expression of
      gp91(phox) and p47(phox), is involved in the oxidative stress in cisplatin
      induced nephrotoxicity.

PMID- 25388650
TI  - Clinical impact of a new left bundle branch block following TAVI implantation: 1
      year results of the TAVIK cohort.
AB  - BACKGROUND: Compared with surgical aortic valve replacement, transcatheter aortic
      valve implantation (TAVI) is associated with a higher risk of developing a new
      conduction disorder that necessitates permanent pacemaker implantation (PM). The
      most frequently observed conduction disorder is left bundle branch block (LBBB),
      which impairs left ventricular function. OBJECTIVES: The primary objective of
      this study was to assess the incidence and prognostic significance of persistent
      new-onset LBBB following TAVI. Factors predictive of persistent new-onset LBBB
      were also explored. METHODS: This study included a total of 793 patients who
      underwent TAVI between May 2008 and April 2012. Patients were divided into two
      groups: those with persistent new-onset LBBB and those without persistent new
      onset LBBB. Follow-up was conducted within 1-year of TAVI. RESULTS: Persistent
      new-onset LBBB was observed in 31.1 % (n = 197) out of 634 eligible patients. At
      30 days and 1-year post-TAVI, the all-cause mortality rate was higher in patients
      with persistent new-onset LBBB (6.1 %, n = 12 and 20.8 %, n = 41, respectively)
      than in patients without new-onset LBBB (3.3 %, n = 10 and 13.0 %, n = 57,
      respectively; p = 0.014 and p = 0.010 for the two time points). Multivariate
      regression analyses revealed, that persistent new-onset LBBB was an independent
      predictor of all-cause mortality at 1 year (HR 1.84, 95 %CI 1.35-2.02). PM
      implantation was observed slightly more frequently in patients with persistent
      new-onset LBBB (14.2 %) than in those without (9.4 %; HR 1.60, 95 %CI 0.96-2.67).
      Risk factors for pacemaker (PM) were baseline RBBB (HR 6.23, 95 %CI 3.76-10.33),
      chronic atrial fibrillation (HR 1.75, 95 %CI 1.10-2.56) and the Medtronic
      CoreValve implantation (HR 2.40, 95 %CI 1.55-3.75). At 1-year follow-up, the mean
      survival of patients with PM (81.2 %) was slightly lower, but not significantly
      different from that of patients without PM (85.0 %; p = 0.377). Upon
      multivariable logistic binary regression analysis Medtronic CoreValve was
      associated with an increase rate of persistent new-onset LBBB (HR 2.52, 95 %CI
      1.67-3.80) and PM implantation. Mortality during 1 year of follow-up, however,
      was neither increased in the total population (p = 0.232), nor in a subgroup of
      those with LBBB in a comparison of Medtronic CoreValve and Edwards SAPIEN.
      CONCLUSION: This study demonstrated that persistent new-onset LBBB was associated
      with increased mortality in patients undergoing TAVI. Compared with the Edwards
      SAPIEN valve, implantation of the Medtronic CoreValve resulted in a higher rate
      of both persistent new-onset LBBB and PM but not death.

PMID- 25388651
TI  - Kinetics of organ response and survival following normalization of the serum free
      light chain ratio in AL amyloidosis.
AB  - Despite successful treatment of the clonal plasma cell implicated in its
      pathogenesis, patients with AL amyloidosis (AL) experience significant morbidity
      related to underlying amyloid mediated organ dysfunction. While normalization of
      the serum free light chain measurements [normal ratio of involved and uninvolved
      free light chains (nFLCr)] is the goal of therapy and centerpiece of hematologic
      response criteria, achieving (or not achieving) meaningful organ response (OR) is
      clinically significant for its implications on long-term symptomatology as well
      as overall survival (OS), and remains the ultimate goal of treatment.
      Expectations for organ recovery following successful therapy leading to nFLCr in
      AL remain poorly described. We evaluated the timeframe and predictive factors for
      OR, and long-term outcome, in 313 AL patients who achieved nFLCr following
      therapy initiation. OR was seen in 80% of surviving AL patients within 1-year of
      nFLCr. Patients achieving early OR within 1 year of nFLCr had superior OS
      compared with those who despite obtaining nFLCr did not achieve early OR. We
      further evaluated factors predicting OR and OS among patients achieving nFLCr.
      Higher values of dFLC (involved-uninvolved) at diagnosis predict OR, and early OR
      predicts improved OS following successful hematologic therapy in AL.

PMID- 25388652
TI  - A computer model of insect traps in a landscape.
AB  - Attractant-based trap networks are important elements of invasive insect
      detection, pest control, and basic research programs. We present a landscape
      level, spatially explicit model of trap networks, focused on detection, that
      incorporates variable attractiveness of traps and a movement model for insect
      dispersion. We describe the model and validate its behavior using field trap data
      on networks targeting two species, Ceratitis capitata and Anoplophora
      glabripennis. Our model will assist efforts to optimize trap networks by 1)
      introducing an accessible and realistic mathematical characterization of the
      operation of a single trap that lends itself easily to parametrization via field
      experiments and 2) allowing direct quantification and comparison of sensitivity
      between trap networks. Results from the two case studies indicate that the
      relationship between number of traps and their spatial distribution and capture
      probability under the model is qualitatively dependent on the attractiveness of
      the traps, a result with important practical consequences. 

PMID- 25388653
TI  - Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune
      mediated killing of tumor cells and immune tumor microenvironment permissiveness
      when combined with a cancer vaccine.
AB  - BACKGROUND: Growing awareness of the complexity of carcinogenesis has made
      multimodal therapies for cancer increasingly compelling and relevant. In recent
      years, immunotherapy has gained acceptance as an active therapeutic approach to
      cancer treatment, even though cancer is widely considered an immunosuppressive
      disease. Combining immunotherapy with targeted agents that have immunomodulatory
      capabilities could significantly improve its efficacy. METHODS: We evaluated the
      ability of cabozantinib, a receptor tyrosine kinase inhibitor, to modulate the
      immune system in vivo as well as alter the phenotype of tumor cells in vitro in
      order to determine if this inhibitor could act synergistically with a cancer
      vaccine. RESULTS: Our studies indicated that cabozantinib altered the phenotype
      of MC38-CEA murine tumor cells, rendering them more sensitive to immune-mediated
      killing. Cabozantinib also altered the frequency of immune sub-populations in the
      periphery as well as in the tumor microenvironment, which generated a more
      permissive immune environment. When cabozantinib was combined with a poxviral
      based cancer vaccine targeting a self-antigen, the combination significantly
      reduced the function of regulatory T cells and increased cytokine production from
      effector T cells in response to the antigen. These alterations to the immune
      landscape, along with direct modification of tumor cells, led to markedly
      improved antitumor efficacy. CONCLUSIONS: These studies support the clinical
      combination of cabozantinib with immunotherapy for the treatment of cancer.

PMID- 25388654
TI  - Testosterone and body composition in men after treatment for rectal cancer.
AB  - INTRODUCTION: Preoperative radiotherapy for rectal cancer may affect Leydig cell
      function. However, the diagnosis of posttreatment hypogonadism is complicated as
      sexual symptoms associated to hypogonadism can rely on adverse events of pelvic
      radiation and surgery. AIM: The objective of this study was to investigate the
      association of testosterone levels and body composition. The clinical value of
      such an association is tested subsequently in the study population. METHODS: This
      was a longitudinal study with prospective registration during 2010-2012 and 1
      year follow up. Men with rectal cancer stage I-III, treated with radiotherapy and
      surgery, were eligible, and 40 of 53 men were available for analysis. MAIN
      OUTCOME MEASURES: The areas of skeletal muscle and adipose tissue were assessed
      on a defined section of a computed tomography at baseline and after 1 year.
      Androgen levels were recorded from morning blood samples. RESULTS: The area of
      skeletal muscle was related to the level of bioavailable testosterone (P = 0.01)
      but not to the level of serum testosterone (P = 0.36). The subcutaneous adipose
      tissue was not related to testosterone levels. Men with posttreatment serum
      testosterone levels of 8-12 nmol/L and longitudinal loss of psoas muscle area had
      a significantly increased luteinizing hormone-testosterone ratio compared with
      those with longitudinal gain of psoas muscle. CONCLUSIONS: The area of psoas
      muscle is related to the unbound fraction of circulating testosterone in men
      treated for rectal cancer. The longitudinal loss of psoas muscle in men with
      borderline levels of serum testosterone seems to be an androgen-related symptom
      associated with compensatory activation of the pituitary-gonadal axis indicating
      a testicular failure in this group of patients.

PMID- 25388655
TI  - Hepatitis C virus NS5A drives a PTEN-PI3K/Akt feedback loop to support cell
      survival.
AB  - BACKGROUND & AIMS: Decreased levels of phosphatase and tensin homologue (PTEN)
      are associated with hepatocellular carcinoma (HCC) pathogenesis and poor
      prognosis in hepatitis C virus (HCV)-infected HCC patients. The molecular
      processes governing the reduction in PTEN and outcome of PTEN dysfunction in
      hepatocytes are poorly understood. METHODS: The levels of proteins and mRNA were
      assessed by real time PCR and immunoblot. PTEN promoter activity was measured by
      reporter assay. Signalling pathways were perturbed using siRNAs or
      pharmacological inhibitors. RESULTS: Here, we report that HCV down-regulates PTEN
      expression at the transcriptional level by decreasing its promoter activity, mRNA
      transcription, and protein levels. We further identify NS5A protein as a key
      determinant of PTEN reduction among HCV proteins. NS5A-mediated down-regulation
      of PTEN occurs through a cooperation of reactive oxygen species (ROS)-dependent
      Nuclear Factor- kappa B (NF-kappaB) and ROS-independent phosphoinositol-3-kinase
      (PI3K) pathways. Moreover, NS5A protects cells against apoptosis. In addition, we
      found that down-regulation of PTEN relieves its inhibitory effect on PI3K-Akt
      pathway and triggers cumulative activation of Akt. This PTEN-PI3K/Akt feedback
      network mediates the suppression of cell apoptosis caused by NS5A. CONCLUSIONS:
      These data demonstrate that HCV NS5A down-regulates PTEN expression through a
      cooperation of ROS-dependent and -independent pathways that subsequently drives a
      PTEN-PI3K/Akt feedback loop to support cell survival. Our findings provide new
      insights suggesting that NS5A contributes to HCV-related hepatocarcinogenesis.

PMID- 25388656
TI  - The predictive value of single-photon emission computed tomography/computed
      tomography for sentinel lymph node localization in head and neck cutaneous
      malignancy.
AB  - OBJECTIVES/HYPOTHESIS: Preoperative localization of sentinel lymph nodes in head
      and neck cutaneous malignancies can be aided by single-photon emission computed
      tomography/computed tomography (SPECT/CT); however, its true predictive value for
      identifying lymph nodes intraoperatively remains unquantified. This study aims to
      understand the sensitivity, specificity, and positive and negative predictive
      values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of
      the head and neck. STUDY DESIGN: Blinded retrospective imaging review with
      comparison to intraoperative gamma probe confirmed sentinel lymph nodes. METHODS:
      A consecutive series of patients with a head and neck cutaneous malignancy
      underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a
      gamma probe. Two nuclear medicine physicians, blinded to clinical data,
      independently reviewed each SPECT/CT. Activity within radiographically defined
      nodal basins was recorded and compared to intraoperative gamma probe findings.
      Sensitivity, specificity, and negative and positive predictive values were
      calculated with subgroup stratification by primary tumor site. RESULTS: Ninety
      two imaging reads were performed on 47 patients with cutaneous malignancy who
      underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity
      was 73%, specificity 92%, positive predictive value 54%, and negative predictive
      value 96%. The predictive ability of SPECT/CT to identify the basin or an
      adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated
      uptake by an average of one nodal basin. In the head and neck, SPECT/CT has
      higher reliability for primary lesions of the eyelid, scalp, and cheek.
      CONCLUSIONS: SPECT/CT has high sensitivity, specificity, and negative predictive
      value, but may overestimate relevant nodal basins in sentinel lymph node biopsy.

PMID- 25388657
TI  - Synthesis and photophysical properties of a Sc3N@C80 -corrole electron donor
      acceptor conjugate.
AB  - Embedding endohdedral metallofullerenes (EMFs) into electron donor-acceptor
      systems is still a challenging task owing to their limited quantities and their
      still largely unexplored chemical properties. In this study, we have performed a
      1,3-dipolar cycloaddition reaction of a corrole-based precursor with Sc3 N@C80 to
      regioselectively form a [5,6]-adduct (1). The successful attachment of the
      corrole moiety was confirmed by mass spectrometry. In the electronic ground
      state, absorption spectra suggest sizeable electronic communications between the
      electron acceptor and the electron donor. Moreover, the addition pattern
      occurring at a [5,6]-bond junction is firmly proven by NMR spectroscopy and
      electrochemical investigations performed with 1. In the electronically excited
      state, which is probed in photophysical assays with 1, a fast electron-transfer
      yields the radical ion pair state consisting of the one-electron-reduced Sc3
      N@C80 and of the one-electron-oxidized corrole upon its exclusive
      photoexcitation. As such, our results shed new light on the practical work
      utilizing EMFs as building blocks in photovoltaics. 

PMID- 25388658
TI  - Ensuring continued progress in biomarkers for amyotrophic lateral sclerosis:
      another view.

PMID- 25388659
TI  - Predictors of outcome after surgery for gastric cancer in a Western cohort.
AB  - BACKGROUND: Gastric cancer (GC) is a common cause of cancer mortality. There are
      well-documented prognostic factors for GC but these have not been rigorously
      examined in an Australian context. This study examines the clinical, surgical and
      histopathological variables associated with survival in a GC cohort from a
      predominantly Caucasian-based population. METHODS: A multi-centre cohort of
      patients undergoing curative resection for GC enrolled in an ongoing tissue bank
      study from 1999 to 2009 was retrospectively analysed. Prospectively collected
      demographic, surgical and pathological variables were available for this cohort.
      The primary endpoints investigated were cancer-specific survival and recurrence
      free survival using multivariate Cox proportional hazard modelling. RESULTS: Five
      year cancer-specific survival was 45.9%, 5-year relapse-free survival was 44.7%
      and 30-day mortality was 2.2%. Variables showing significance on multivariate
      analysis for cancer-specific and relapse-free survival were AJCC stage, Lauren
      classification and age at surgery. CONCLUSION: This study demonstrates that the
      prognostic variables for a predominantly Caucasian GC population are congruent
      with published prognostic features. These findings emphasize the importance of
      the pathological review in allocating prognosis in GC.

PMID- 25388660
TI  - MObile Technology for Improved Family Planning: update to randomised controlled
      trial protocol.
AB  - BACKGROUND: This update outlines changes to the MObile Technology for Improved
      Family Planning study statistical analysis plan and plans for long-term follow
      up. These changes result from obtaining additional funding and the decision to
      restrict the primary analysis to participants with available follow-up data. The
      changes were agreed prior to finalising the statistical analysis plan and sealing
      the dataset. METHODS/DESIGN: The primary analysis will now be restricted to
      subjects with data on the primary outcome at 4-month follow-up. The extreme-case
      scenario, where all those lost to follow-up are counted as non-adherent, will be
      used in a sensitivity analysis. In addition to the secondary outcomes outlined in
      the protocol, we will assess the effect of the intervention on long-acting
      contraception (implant, intra-uterine device and permanent methods).To assess the
      long-term effect of the intervention, we plan to conduct additional 12-month
      follow-up by telephone self-report for all the primary and secondary outcomes
      used at 4 months. All participants provided informed consent for this additional
      follow-up when recruited to the trial. Outcome measures and analysis at 12 months
      will be similar to those at the 4-month follow-up. The primary outcomes of the
      trial will be the use of an effective modern contraceptive method at 4 months and
      at 12 months post-abortion. Secondary outcomes will include long-acting
      contraception use, self-reported pregnancy, repeat abortion and contraception use
      over the 12-month post-abortion period. DISCUSSION: Restricting the primary
      analysis to those with follow-up data is the standard approach for trial analysis
      and will facilitate comparison with other trials of interventions designed to
      increase contraception uptake or use. Undertaking 12-month trial follow-up will
      allow us to evaluate the long-term effect of the intervention. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01823861.

PMID- 25388661
TI  - Modulation of Posterior Alpha Activity by Spatial Attention Allows for
      Controlling A Continuous Brain-Computer Interface.
AB  - Here we report that the modulation of alpha activity by covert attention can be
      used as a control signal in an online brain-computer interface, that it is
      reliable, and that it is robust. Subjects were instructed to orient covert visual
      attention to the left or right hemifield. We decoded the direction of attention
      from the magnetoencephalogram by a template matching classifier and provided the
      classification outcome to the subject in real-time using a novel graphical user
      interface. Training data for the templates were obtained from a Posner-cueing
      task conducted just before the BCI task. Eleven subjects participated in four
      sessions each. Eight of the subjects achieved classification rates significantly
      above chance level. Subjects were able to significantly increase their
      performance from the first to the second session. Individual patterns of
      posterior alpha power remained stable throughout the four sessions and did not
      change with increased performance. We conclude that posterior alpha power can
      successfully be used as a control signal in brain-computer interfaces. We also
      discuss several ideas for further improving the setup and propose future research
      based on solid hypotheses about behavioral consequences of modulating neuronal
      oscillations by brain computer interfacing.

PMID- 25388662
TI  - Review of Climate Change and Water-Related Diseases in Cambodia and Findings From
      Stakeholder Knowledge Assessments.
AB  - This project aims to increase the resilience of Cambodian communities to the
      health risks posed by climate change-related impacts on water-related diseases.
      There are a number of water-related diseases that are present in Cambodia and are
      likely to be susceptible to climate change. These include diarrheal diseases,
      typhoid fever, leptospirosis, melioidosis, viral hepatitis, and schistosomiasis.
      Certain subsectors of Cambodia's population may be more vulnerable than others
      with respect to climate change impacts on water and health, including
      agricultural workers and residents of flood-and drought-prone areas. The current
      level of understanding on the part of health professionals and other key
      stakeholders in Cambodia regarding the risks posed by climate change on water
      sensitive diseases is relatively low. Strategies by which this understanding
      might be strengthened are suggested. 

PMID- 25388663
TI  - Cardiovascular research as a forum for publications from China: present, past,
      and future.

PMID- 25388664
TI  - Identification of PI3K regulatory subunit p55gamma as a novel inhibitor of
      vascular smooth muscle cell proliferation and neointimal formation.
AB  - AIMS: Phosphatidylinositol 3 kinases (PI3Ks) play a pivotal role in vascular
      physiology and pathophysiology. We aimed to investigate the role of p55gamma, a
      regulatory subunit of PI3Ks, in vascular smooth muscle cell (VSMC) proliferation
      and neointimal formation. METHODS AND RESULTS: We identified p55gamma as an
      important factor that suppresses VSMC proliferation and injury-evoked neointimal
      formation. Western blot and mRNA analyses showed that p55gamma expression
      declined in balloon-injured rat carotid arteries and in response to PDGF-BB and
      serum treatment in cultured VSMCs. Overexpression of p55gamma inhibited, whereas
      short hairpin RNA knockdown of p55gamma promoted PDGF-BB- and serum-induced VSMC
      proliferation. Importantly, in vivo adenoviral gene transfer of p55gamma into
      carotid arteries attenuated, while knockdown of p55gamma enhanced balloon injury
      induced neointimal formation. Furthermore, p55gamma sequentially up-regulated p53
      and p21, resulting in cell-cycle arrest in S phase; small-interfering RNA
      knockdown of either p53 or p21 blocked p55gamma-induced VSMC growth arrest.
      Mechanistically, p55gamma interacted with and stabilized p53 protein by blocking
      mouse double minute 2 homologue-mediated p53 ubiquitination and degradation,
      subsequently activating its target gene p21. Concurrently, p55gamma up-regulated
      Bcl-xl expression, resulting in non-apoptotic growth arrest effect. CONCLUSION:
      These findings mark p55gamma as a novel upstream regulator of the p53-p21
      signalling pathway that negatively regulates VSMC proliferation, suggesting that
      malfunction of p55gamma may trigger vascular proliferative disorders.

PMID- 25388665
TI  - FGFR1 mediates recombinant thrombomodulin domain-induced angiogenesis.
AB  - AIMS: The recombinant epidermal growth factor-like domain plus the
      serine/threonine-rich domain of thrombomodulin (rTMD23) promotes angiogenesis and
      accelerates the generation of activated protein C (APC), which facilitates
      angiogenesis. The aim of this study was to elucidate the molecular mechanisms
      underlying the angiogenic activity of rTMD23. METHODS AND RESULTS: We prepared
      rTMD23 and its mutants that did not possess the ability to promote APC generation
      and investigated their angiogenic activities in vitro and in vivo. rTMD23 mutants
      promoted proliferation, migration, and tube formation of human umbilical vein
      endothelial cells in vitro and induced neovascularization in vivo; these effects
      were similar to those exerted by wild-type rTMD23. To investigate its interaction
      with rTMD23, Type I fibroblast growth factor receptor (FGFR1) was precipitated
      along with syndecan-4 by rTMD23-conjugated Sepharose in human umbilical vein
      endothelial cells and FGFR1-expressing human embryonic kidney 293 cells.
      Additionally, the kinetics of the interaction between rTMD23 and FGFR1 were
      analysed using surface plasmon resonance. rTMD23-induced FGFR1 activation and
      tube formation were inhibited by an FGFR1-specific tyrosine kinase inhibitor,
      PD173074, or by knockdown of FGFR1 using siRNA technology. We observed an
      improvement in rat hindlimb recovery in an ischaemic model following rTMD23
      treatment, and this was associated with increased neovascularization and FGFR1
      phosphorylation. CONCLUSION: rTMD23 induced angiogenesis via FGFR1, a process
      that is independent of the APC pathway.

PMID- 25388666
TI  - Erk5 inhibits endothelial migration via KLF2-dependent down-regulation of PAK1.
AB  - AIMS: The MEK5/Erk5 pathway mediates beneficial effects of laminar flow, a major
      physiological factor preventing vascular dysfunction. Forced Erk5 activation
      induces a protective phenotype in endothelial cell (EC) that is associated with a
      dramatically decreased migration capacity of those cells. Transcriptional
      profiling identified the Kruppel-like transcription factors KLF2 and KLF4 as
      central mediators of Erk5-dependent gene expression. However, their downstream
      role regarding migration is unclear and relevant secondary effectors remain
      elusive. Here, we further investigated the mechanism underlying Erk5-dependent
      migration arrest in ECs. METHODS AND RESULTS: Our experiments reveal KLF2
      dependent loss of the pro-migratory Rac/Cdc42 mediator, p21-activated kinase 1
      (PAK1), as an important mechanism of Erk5-induced migration inhibition. We show
      that endothelial Erk5 activation by expression of a constitutively active MEK5
      mutant, by statin treatment, or by application of laminar shear stress strongly
      decreased PAK1 mRNA and protein expression. Knockdown of KLF2 but not of KLF4
      prevented Erk5-mediated PAK1 mRNA inhibition, revealing KLF2 as a novel PAK1
      repressor in ECs. Importantly, both PAK1 re-expression and KLF2 knockdown
      restored the migration capacity of Erk5-activated ECs underscoring their
      functional relevance downstream of Erk5. CONCLUSION: Our data provide first
      evidence for existence of a previously unknown Erk5/KLF2/PAK1 axis, which may
      limit undesired cell migration in unperturbed endothelium and lower its
      sensitivity for migratory cues that promote vascular diseases including
      atherosclerosis.

PMID- 25388668
TI  - Automated effective band structures for defective and mismatched supercells.
AB  - In plane-wave density functional theory codes, defects and incommensurate
      structures are usually represented in supercells. However, interpretation of E
      versus k band structures is most effective within the primitive cell, where
      comparison to ideal structures and spectroscopy experiments are most natural.
      Popescu and Zunger recently described a method to derive effective band
      structures (EBS) from supercell calculations in the context of random alloys. In
      this paper, we present bs_sc2pc, an implementation of this method in the CASTEP
      code, which generates an EBS using the structural data of the supercell and the
      underlying primitive cell with symmetry considerations handled automatically. We
      demonstrate the functionality of our implementation in three test cases
      illustrating the efficacy of this scheme for capturing the effect of vacancies,
      substitutions and lattice mismatch on effective primitive cell band structures.

PMID- 25388669
TI  - Anomalous modulation of photoinduced electron transfer of coumarin 102 in aniline
      dimethylaniline mixture: dominant role of hydrogen bonding.
AB  - In a previous study, we reported a striking observation that photoinduced
      electron transfer (PET) from aniline (AN) to photoexcited coumarin 102 (C102) can
      be accelerated by adding an inert component (cyclohexane or toluene) to the neat
      electron donor solvent AN (Phys. Chem. Chem. Phys., 2014, 16, 6159-6166). The H
      bond linking the electron donor (D, AN) and the acceptor (A, C102) was proposed
      to dictate the PET process. To account for the unusual variation of quenching
      pattern with AN mole fraction, two possible reasons were cited - (1) the D-A (AN
      C102) H-bonding may be modulated due to change in polarity of the medium or (2)
      the additional D-D (AN-AN) H-bonding may restrain the D-A H-bonding to adjust
      optimally for the PET. Here, we investigate the PET of C102 in an AN
      dimethylaniline (DMA) mixture to negate the polarity variation. Since, both AN
      and DMA have similar polarities, the polarity of the mixture should remain
      invariant at all compositions. Nevertheless, we found that the fluorescence
      quantum yield and lifetime of C102 in the mixtures follows a similar unusual
      trend as observed earlier in the AN-toluene or AN-cyclohexane mixtures; it first
      decreases up to a particular mole fraction (XD) of the H-bond donor AN and,
      thereafter, increases on further enrichment of the donor. The observed PET
      modulation may be rationalized by considering efficient PET in the 1 : 1 H-bonded
      C102-AN complex but less efficient PET in higher order C102-(AN)n>=2 complexes,
      where additional D-D (AN-AN) H-bonding may influence the key C102-AN H-bonding
      and thus inhibit the PET process. 

PMID- 25388671
TI  - Erratum to: The WHO ultrasonography protocol for assessing hepatic morbidity due
      to Schistosoma mansoni. Acceptance and evolution over 12 years.

PMID- 25388670
TI  - Whole-genome enrichment and sequencing of Chlamydia trachomatis directly from
      clinical samples.
AB  - BACKGROUND: Chlamydia trachomatis is a pathogen of worldwide importance, causing
      more than 100 million cases of sexually transmitted infections annually. Whole
      genome sequencing is a powerful high resolution tool that can be used to generate
      accurate data on bacterial population structure, phylogeography and mutations
      associated with antimicrobial resistance. The objective of this study was to
      perform whole-genome enrichment and sequencing of C. trachomatis directly from
      clinical samples. METHODS: C. trachomatis positive samples comprising seven
      vaginal swabs and three urine samples were sequenced without prior in vitro
      culture in addition to nine cultured C. trachomatis samples, representing
      different serovars. A custom capture RNA bait set, that captures all known
      diversity amongst C. trachomatis genomes, was used in a whole-genome enrichment
      step during library preparation to enrich for C. trachomatis DNA. All samples
      were sequenced on the MiSeq platform. RESULTS: Full length C. trachomatis genomes
      (>95-100% coverage of a reference genome) were successfully generated for eight
      of ten clinical samples and for all cultured samples. The proportion of reads
      mapping to C. trachomatis and the mean read depth across each genome were
      strongly linked to the number of bacterial copies within the original sample.
      Phylogenetic analysis confirmed the known population structure and the data
      showed potential for identification of minority variants and mutations associated
      with antimicrobial resistance. The sensitivity of the method was >10-fold higher
      than other reported methodologies. CONCLUSIONS: The combination of whole-genome
      enrichment and deep sequencing has proven to be a non-mutagenic approach,
      capturing all known variation found within C. trachomatis genomes. The method is
      a consistent and sensitive tool that enables rapid whole-genome sequencing of C.
      trachomatis directly from clinical samples and has the potential to be adapted to
      other pathogens with a similar clonal nature.

PMID- 25388672
TI  - Size and placement of developing anterior teeth in immature Neanderthal mandibles
      from Dederiyeh Cave, Syria: implications for emergence of the modern human chin.
AB  - Evolutionary and functional significance of the human chin has long been explored
      from various perspectives including masticatory biomechanics, speech, and
      anterior tooth size. Recent ontogenetic studies have indicated that the spatial
      position of internally forming anterior teeth partially constrains adult
      mandibular symphyseal morphology. The present study therefore preliminarily
      examined the size and placement of developing anterior teeth in immature
      Neanderthal mandibles of Dederiyeh 1 and 2, compared with similarly-aged modern
      humans (N = 16) and chimpanzees (N = 7) whose incisors are comparatively small
      and large among extant hominids, respectively. The Dederiyeh 1 mandible is
      described as slightly presenting a mental trigone and attendant mental fossa,
      whereas Dederiyeh 2 completely lacks such chin-associated configurations. Results
      showed that, despite symphyseal size being within the modern human range, both
      Dederiyeh mandibles accommodated overall larger anterior dentition and displayed
      a remarkably wide bicanine space compared to those of modern humans. Dederiyeh 2
      had comparatively thicker deciduous incisor roots and more enlarged permanent
      incisor crypts than Dederiyeh 1, but both Dederiyeh individuals exhibited a total
      dental size mostly intermediate between modern humans and chimpanzees. These
      findings potentially imply that the large deciduous/permanent incisors
      collectively distended the labial alveolar bone, obscuring an incipient mental
      trigone. It is therefore hypothesized that the appearance of chin-associated
      features, particularly of the mental trigone and fossa, can be accounted for
      partly by developmental relationships between the sizes of the available
      mandibular space and anterior teeth. This hypothesis must be, however, further
      addressed with more referential samples in future studies.

PMID- 25388673
TI  - Climate change and long-term fire management impacts on Australian savannas.
AB  - Tropical savannas cover a large proportion of the Earth's land surface and many
      people are dependent on the ecosystem services that savannas supply. Their
      sustainable management is crucial. Owing to the complexity of savanna vegetation
      dynamics, climate change and land use impacts on savannas are highly uncertain.
      We used a dynamic vegetation model, the adaptive dynamic global vegetation model
      (aDGVM), to project how climate change and fire management might influence future
      vegetation in northern Australian savannas. Under future climate conditions,
      vegetation can store more carbon than under ambient conditions. Changes in
      rainfall seasonality influence future carbon storage but do not turn vegetation
      into a carbon source, suggesting that CO2 fertilization is the main driver of
      vegetation change. The application of prescribed fires with varying return
      intervals and burning season influences vegetation and fire impacts. Carbon
      sequestration is maximized with early dry season fires and long fire return
      intervals, while grass productivity is maximized with late dry season fires and
      intermediate fire return intervals. The study has implications for management
      policy across Australian savannas because it identifies how fire management
      strategies may influence grazing yield, carbon sequestration and greenhouse gas
      emissions. This knowledge is crucial to maintaining important ecosystem services
      of Australian savannas.

PMID- 25388674
TI  - Developmental guidelines for good chairside teaching - a consensus report from
      two conferences.
AB  - Developmental Guidelines for Chairside Teaching are a direct outcome of 10 years
      of research, originally prompted by feedback from undergraduate dental students
      who not only thought that the teaching they received was uneven and variable in
      quality, but also felt strongly that they learned more with educationally trained
      teachers than those with little or no teacher training. Workshops embracing the
      views of teaching colleagues from many other Dental Schools produced a consensus
      view that developmental guidelines for teachers would provide a valuable
      resource. A conference to consider all aspects on chairside teaching and learning
      was convened with delegates invited from all UK Dental Schools. This was
      subsequently followed by a second conference to develop specific guidelines for
      chairside teaching and learning. The Nominal Group Technique was used in the
      first chairside teaching conference, and Structured Small Expert Groups were used
      in the second. The overall consensus from these workshops and conferences were as
      follows: (i) developmental guidelines for chairside teaching can act as a useful
      resource for teachers to improve and maintain their standard of chairside
      teaching, (ii) developmental guidelines can be divided into themes of
      organisational issues and learner and teacher qualities, and (iii) Guidelines
      should be 'developmental' because they encourage chairside teachers to focus on
      the next immediate goal to maintain and improve quality and standards. These
      developmental guidelines could provide a universal toolkit for improved chairside
      teaching which would result in a better student learning experience. Set out in
      this way these guidelines have currency across academic and practical skills
      levels, different educational systems, philosophies and country boundaries.

PMID- 25388675
TI  - CpG preconditioning regulates miRNA expression that modulates genomic
      reprogramming associated with neuroprotection against ischemic injury.
AB  - Cytosine-phosphate-guanine (CpG) preconditioning reprograms the genomic response
      to stroke to protect the brain against ischemic injury. The mechanisms underlying
      genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate
      gene expression; however, their role in modulating gene responses produced by CpG
      preconditioning is unknown. We evaluated brain miRNA expression in response to
      CpG preconditioning before and after stroke using microarray. Importantly, we
      have data from previous gene microarrays under the same conditions, which allowed
      integration of miRNA and gene expression data to specifically identify regulated
      miRNA gene targets. CpG preconditioning did not significantly alter miRNA
      expression before stroke, indicating that miRNA regulation is not critical for
      the initiation of preconditioning-induced neuroprotection. However, after stroke,
      differentially regulated miRNAs between CpG- and saline-treated animals
      associated with the upregulation of several neuroprotective genes, implicating
      these miRNAs in genomic reprogramming that increases neuroprotection. Statistical
      analysis revealed that the miRNA targets were enriched in the gene population
      regulated in the setting of stroke, implying that miRNAs likely orchestrate this
      gene expression. These data suggest that miRNAs regulate endogenous responses to
      stroke and that manipulation of these miRNAs may have the potential to acutely
      activate novel neuroprotective processes that reduce damage. 

PMID- 25388676
TI  - Cerebral autoregulation and brain networks in occlusive processes of the internal
      carotid artery.
AB  - Patients with unilateral occlusive processes of the internal carotid artery (ICA)
      show subtle cognitive deficits. Decline in cerebral autoregulation and in
      functional and structural integrity of brain networks have previously been
      reported in the affected hemisphere (AH). However, the association between
      cerebral autoregulation, brain networks, and cognition remains to be elucidated.
      Fourteen neurologically asymptomatic patients (65+/-11 years) with either ICA
      occlusion or high-grade ICA stenosis and 11 age-matched healthy controls (HC)
      (67+/-6 years) received neuropsychologic testing, transcranial Doppler sonography
      to assess cerebral autoregulation using vasomotor reactivity (VMR), and magnetic
      resonance imaging to probe white matter microstructure and resting-state
      functional connectivity (RSFC). Patients performed worse on memory and executive
      tasks when compared with controls. Vasomotor reactivity, white matter
      microstructure, and RSFC were lower in the AH of the patients when compared with
      the unaffected hemisphere and with controls. Lower VMR of the AH was associated
      with several ipsilateral clusters of lower white matter microstructure and lower
      bilateral RSFC in patients. No correlations were found between VMR and cognitive
      scores. In sum, impaired cerebral autoregulation was associated with reduced
      structural and functional connectivity in cerebral networks, indicating possible
      mechanisms by which severe unilateral occlusive processes of the ICA lead to
      cognitive decline. 

PMID- 25388677
TI  - Effect of age and vascular anatomy on blood flow in major cerebral vessels.
AB  - Measurement of volume flow rates in major cerebral vessels can be used to
      evaluate the hemodynamic effects of cerebrovascular disease. However, both age
      and vascular anatomy can affect flow rates independent of disease. We
      prospectively evaluated 325 healthy adult volunteers using phase contrast
      quantitative magnetic resonance angiography to characterize these effects on
      cerebral vessel flow rates and establish clinically useful normative reference
      values. Flows were measured in the major intracranial and extracranial vessels.
      The cohort ranged from 18 to 84 years old, with 157 (48%) females. All individual
      vessel flows and total cerebral blood flow (TCBF) declined with age, at 2.6
      mL/minute per year for TCBF. Basilar artery (BA) flow was significantly decreased
      in individuals with one or both fetal posterior cerebral arteries (PCAs).
      Internal carotid artery flows were significantly higher with a fetal PCA and
      decreased with a hypoplastic anterior cerebral artery. Indexing vessel flows to
      TCBF neutralized the age effect, but anatomic variations continued to impact
      indexed flow in the BA and internal carotid artery. Variability in normative flow
      ranges were reduced in distal vessels and by examining regional flows. Cerebral
      vessel flows are affected by age and cerebrovascular anatomy, which has important
      implications for interpretation of flows in the disease state.

PMID- 25388678
TI  - Patterned optogenetic modulation of neurovascular and metabolic signals.
AB  - The hemodynamic and metabolic response of the cortex depends spatially and
      temporally on the activity of multiple cell types. Optogenetics enables specific
      cell types to be modulated with high temporal precision and is therefore an
      emerging method for studying neurovascular and neurometabolic coupling. Going
      beyond temporal investigations, we developed a microprojection system to apply
      spatial photostimulus patterns in vivo. We monitored vascular and metabolic
      fluorescence signals after photostimulation in Thy1-channelrhodopsin-2 mice.
      Cerebral arteries increased in diameter rapidly after photostimulation, while
      nearby veins showed a slower smaller response. The amplitude of the arterial
      response was depended on the area of cortex stimulated. The fluorescence signal
      emitted at 450/100 nm and excited with ultraviolet is indicative of reduced
      nicotinamide adenine dinucleotide, an endogenous fluorescent enzyme involved in
      glycolysis and the citric acid cycle. This fluorescence signal decreased quickly
      and transiently after optogenetic stimulation, suggesting that glucose metabolism
      is tightly locked to optogenetic stimulation. To verify optogenetic stimulation
      of the cortex, we used a transparent substrate microelectrode array to map
      cortical potentials resulting from optogenetic stimulation. Spatial optogenetic
      stimulation is a new tool for studying neurovascular and neurometabolic coupling.

PMID- 25388679
TI  - Assessing cerebrovascular reactivity abnormality by comparison to a reference
      atlas.
AB  - Attribution of vascular pathophysiology to reductions in cerebrovascular
      reactivity (CVR) is confounded by subjective assessment and the normal variation
      between anatomic regions. This study aimed to develop an objective scoring
      assessment of abnormality. CVR was measured as the ratio of the blood-oxygen
      level-dependent magnetic resonance signal response divided by an increase in CO2,
      standardized to eliminate variability. A reference normal atlas was generated by
      coregistering the CVR maps from 46 healthy subjects into a standard space and
      calculating the mean and standard deviation (s.d.) of CVR for each voxel. Example
      CVR studies from 10 patients with cerebral vasculopathy were assessed for
      abnormality, by normalizing each patient's CVR to the same standard space as the
      atlas, and assigning a z-score to each voxel relative to the mean and s.d. of the
      corresponding atlas voxel. Z-scores were color coded and superimposed on their
      anatomic scans to form CVR z-maps. We found the CVR z-maps provided an objective
      evaluation of abnormality, enhancing our appreciation of the extent and
      distribution of pathophysiology compared with CVR maps alone. We concluded that
      CVR z-maps provide an objective, improved form of evaluation for comparisons of
      voxel-specific CVR between subjects, and across tests sites. 

PMID- 25388680
TI  - Genetic markers in the EET metabolic pathway are associated with outcomes in
      patients with aneurysmal subarachnoid hemorrhage.
AB  - Preclinical studies show that epoxyeicosatrienoic acids (EETs) regulate
      cerebrovascular tone and protect against cerebral ischemia. We investigated the
      relationship between polymorphic genes involved in EET biosynthesis/metabolism,
      cytochrome P450 (CYP) eicosanoid levels, and outcomes in 363 patients with
      aneurysmal subarachnoid hemorrhage (aSAH). Epoxyeicosatrienoic acids and
      dihydroxyeicosatetraenoic acid (DHET) cerebrospinal fluid (CSF) levels, as well
      as acute outcomes defined by delayed cerebral ischemia (DCI) or clinical
      neurologic deterioration (CND), were assessed over 14 days. Long-term outcomes
      were defined by Modified Rankin Scale (MRS) at 3 and 12 months. CYP2C8*4 allele
      carriers had 44% and 36% lower mean EET and DHET CSF levels (P=0.003 and P=0.007)
      and were 2.2- and 2.5-fold more likely to develop DCI and CND (P=0.039 and
      P=0.041), respectively. EPHX2 55Arg, CYP2J2*7, CYP2C8*1B, and CYP2C8 g.36785A
      allele carriers had lower EET and DHET CSF levels. CYP2C8 g.25369T and CYP2C8
      g.36755A allele carriers had higher EET levels. Patients with CYP2C8*2C and EPHX2
      404del variants had worse long-term outcomes while those with EPHX2 287Gln,
      CYP2J2*7, and CYP2C9 g.816G variants had favorable outcomes. Epoxyeicosatrienoic
      acid levels were associated with Fisher grade and unfavorable 3-month outcomes.
      Dihydroxyeicosatetraenoic acids were not associated with outcomes. No
      associations passed Bonferroni multiple testing correction. These are the first
      clinical data demonstrating the association between the EET
      biosynthesis/metabolic pathway and the pathophysiology of aSAH.

PMID- 25388682
TI  - Magnetic resonance imaging characteristics of intramuscular lipomas.

PMID- 25388681
TI  - Sex differences in ischemic stroke sensitivity are influenced by gonadal
      hormones, not by sex chromosome complement.
AB  - Epidemiologic studies have shown sex differences in ischemic stroke. The four
      core genotype (FCG) mouse model, in which the testes determining gene, Sry, has
      been moved from Y chromosome to an autosome, was used to dissociate the effects
      of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral
      artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM
      and XYM) had significantly higher infarct volumes as compared with gonadal
      females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and
      XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal
      hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy
      significantly increased infarct volumes in females, while no change was seen in
      gonadectomized males, indicating that estrogen loss increases ischemic
      sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this
      phenotype. Interestingly, FCG male mice were less sensitive to effects of
      hormones. This may be due to enhanced expression of the transgene Sry in brains
      of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be
      shaped by organizational and activational effects of sex hormones, rather than
      sex chromosomal complement. 

PMID- 25388684
TI  - Retrospective cohort of trisomy 18 (Edwards syndrome) in southern Brazil.
AB  - CONTEXT AND OBJECTIVE: Trisomy 18 (T18), or Edwards syndrome, is a chromosomal
      disease characterized by a broad clinical picture and a poor prognosis. Our aim
      was to describe clinical, radiological and survival data of a cohort of patients
      prenatally diagnosed with T18. DESIGN AND SETTING: Retrospective single cohort in
      the Fetal Medicine Service of Hospital Materno Infantil Presidente Vargas
      (HMIPV). METHODS: All sequential patients with T18 registered at the Fetal
      Medicine Service of HMIPV between January 2005 and September 2013 were
      considered. We gathered their clinical, radiological and survival data and used
      the Kaplan-Meier test for survival analysis. RESULTS: Ten patients were diagnosed
      with T18, of whom seven (70%) were female. The majority (90%) were referred due
      to malformations seen on ultrasound. The mean gestational age at the first
      evaluation was 25.5 weeks. At karyotyping, the defects were considered multiple
      in only four patients (40%). All the fetuses presented full trisomy of chromosome
      18. The main abnormality observed was congenital heart disease (n = 7).
      Intrauterine death occurred in half of the patients (50%). All live patients (n =
      5) were born through cesarean section presenting low weight and low Apgar scores.
      The median length of survival after birth was 18 days. CONCLUSIONS: T18 is
      associated with a high risk of fetal and neonatal death. The majority of the
      patients present major malformations identified through ultrasound, such as
      congenital heart defects, which could help in identifying such cases prenatally.

PMID- 25388685
TI  - Overview of systematic reviews - a new type of study. Part II.
AB  - CONTEXT AND OBJECTIVE: Overviews of Systematic Reviews (OoRs) are a new type of
      study in which multiple evidence from systematic reviews (SRs) is compiled into
      an accessible and useful document. The aim here was to describe the state of the
      art and critically assess Cochrane OoRs that have been published. DESIGN AND
      SETTING: Descriptive study conducted at a research center. METHODS: The OoRs
      identified through the filter developed in Part I of this study were evaluated in
      five domains: methodological quality; quality of evidence; implications for
      practice; general profile of OoRs; and length of work. RESULTS: All 13 OoRs
      included had high methodological quality. Some OoRs did not present sufficient
      data to judge the quality of evidence; using sensitivity analysis, the quality of
      evidence of the OoRs increased. Regarding implications for practice, 64% of the
      interventions were judged as beneficial or harmful, while 36% of them showed
      insufficient evidence for judgment. It is expected (with 95% confidence interval)
      that one OoR will include 9,462 to 64,469 patients, 9 to 29 systematic reviews
      and 80 to 344 primary studies, and assess 6 to 21 interventions; and that 50 to
      92% of OoRs will produce meta-analysis. The OoRs generated 2 to 26 meta-analyses
      over a period of 18 to 31 months. CONCLUSION: The OoRs presented high
      methodological quality; the quality of evidence tended to be moderate/high; most
      interventions were judged to be beneficial/harmful; the mean length of work was
      24 months. The OoR profile adds power to decision-making.

PMID- 25388686
TI  - Patients' perceptions about diagnosis and treatment of chronic myeloid leukemia:
      a cross-sectional study among Brazilian patients.
AB  - CONTEXT AND OBJECTIVES: Chronic myeloid leukemia (CML) requires strict daily
      compliance with oral medication and regular blood and bone marrow control tests.
      The objective was to evaluate CML patients' perceptions about the disease, their
      access to information regarding the diagnosis, monitoring and treatment, adverse
      effects and associations of these variables with patients' demographics, region
      and healthcare access. DESIGN AND SETTING: Prospective cross-sectional study
      among CML patients registered with the Brazilian Lymphoma and Leukemia
      Association (ABRALE). METHODS: CML patients receiving treatment through the
      public healthcare system were interviewed by telephone. RESULTS: Among 1,102
      patients interviewed, the symptoms most frequently leading them to seek medical
      care were weakness or fatigue. One third were diagnosed by means of routine
      tests. The time that elapsed between first symptoms and seeking medical care was
      42.28 +/- 154.21 days. Most patients had been tested at least once for
      Philadelphia chromosome, but 43.2% did not know the results. 64.8% had had
      polymerase chain reaction testing for the BCR/ABL gene every three months. 47%
      believed that CML could be controlled, but 33.1% believed that there was no
      treatment. About 24% reported occasionally stopping their medication. Imatinib
      was associated with nausea, cramps and muscle pain. Self-reported treatment
      adherence was significantly associated with normalized blood count, and
      positively associated with imatinib. CONCLUSIONS: There is a lack of information
      or understanding about disease monitoring tools among Brazilian CML patients;
      they are diagnosed quickly and have good access to treatment. Correct
      comprehension of CML control tools is impaired in Brazilian patients.

PMID- 25388688
TI  - Do your bit in the week of action for children.
AB  - It should be obvious that improving the health of the nation's children makes
      sense, but in these days of annualised budgets and rolling news, it is all too
      easy for those running our health service to take short-term decisions. So it is
      good to know that the nurses at Public Health England are striving to ensure that
      our young people's wellbeing is pushed up the agenda. 

PMID- 25388687
TI  - Zinc finger nuclease-mediated gene knockout results in loss of transport activity
      for P-glycoprotein, BCRP, and MRP2 in Caco-2 cells.
AB  - Membrane transporters P-glycoprotein [P-gp; multidrug resistance 1 (MDR1)],
      multidrug resistance-associated protein (MRP) 2, and breast cancer resistance
      protein (BCRP) affect drug absorption and disposition and can also mediate drug
      drug interactions leading to safety/toxicity concerns in the clinic. Challenges
      arise with interpreting cell-based transporter assays when substrates or
      inhibitors affect more than one actively expressed transporter and when
      endogenous or residual transporter activity remains following overexpression or
      knockdown of a given transporter. The objective of this study was to selectively
      knock out three drug efflux transporter genes (MDR1, MRP2, and BCRP), both
      individually as well as in combination, in a subclone of Caco-2 cells (C2BBe1)
      using zinc finger nuclease technology. The wild-type parent and knockout cell
      lines were tested for transporter function in Transwell bidirectional assays
      using probe substrates at 5 or 10 MUM for 2 hours at 37 degrees C. P-gp
      substrates digoxin and erythromycin, BCRP substrates estrone 3-sulfate and
      nitrofurantoin, and MRP2 substrate 5-(and-6)-carboxy-2',7'-dichlorofluorescein
      each showed a loss of asymmetric transport in the MDR1, BCRP, and MRP2 knockout
      cell lines, respectively. Furthermore, transporter interactions were deduced for
      cimetidine, ranitidine, fexofenadine, and colchicine. Compared with the knockout
      cell lines, standard transporter inhibitors showed substrate-specific variation
      in reducing the efflux ratios of the test compounds. These data confirm the
      generation of a panel of stable Caco-2 cell lines with single or double knockout
      of human efflux transporter genes and a complete loss of specific transport
      activity. These cell lines may prove useful in clarifying complex drug
      transporter interactions without some of the limitations of current chemical or
      genetic knockdown approaches. 

PMID- 25388689
TI  - Unison calls off strike after Welsh Government improves its pay offer.
AB  - A strike over pay by nurses and other healthcare workers in Wales has been called
      off after the Welsh Government offered to give NHS staff a 1 per cent
      consolidated pay rise next year. 

PMID- 25388690
TI  - Sculptures honour wartime surgery.
AB  - The Florence Nightingale Museum has marked the centenary of the first world war
      with a display of life-size sculptures of soldiers from different wars who had
      reconstructive surgery after experiencing appalling facial injuries. 

PMID- 25388691
TI  - Senior staff told how their actions contribute to employee stress.
AB  - Employers have been urged to better support nurses and other staff to cut the
      L400 million annual bill for stress-related sickness in the NHS. 

PMID- 25388692
TI  - Anim becomes RCN's first black president.
AB  - The RCN has appointed its first black president. Cecilia Anim, who is deputy to
      Andrea Spyropoulos, will replace her on January 1. 

PMID- 25388693
TI  - CAMHS has 'serious and deeply ingrained problems'.
AB  - Funding to boost the number of school nurses trained to recognise and identify
      early signs of mental illness in children is needed urgently, MPs have said. 

PMID- 25388694
TI  - Nurses rally for assisted dying bill.
AB  - Around 200 nurses, healthcare professionals, terminally ill patients and their
      families demonstrated outside the House of Lords last week in support of Lord
      Falconer's Assisted Dying Bill. 

PMID- 25388695
TI  - MPs slam Macmillan for spending L1m on an integrated care project.
AB  - A leading cancer charity has denied its decision to spend nearly L1 million on an
      NHS project instead of nurses is a misuse of donations, after coming under fire
      from MPs. 

PMID- 25388697
TI  - Cognitive function could be affected by shift work.
AB  - Working shifts can cause long-term memory problems, according to research
      published in the Journal of Occupational and Environmental Medicine. 

PMID- 25388698
TI  - Tackling antibiotic resistance a priority.
AB  - Targets for cutting the use of antibiotics must be introduced as a matter of
      urgency to stop them becoming ineffective, clinicians have said. 

PMID- 25388699
TI  - College and trusts run cadet course.
AB  - A cadet programme that gives school leavers practical experience of nursing and a
      BTEC extended diploma in health and social care has been launched in Cumbria. 

PMID- 25388700
TI  - NICE guidance outlines protocols to stop repeat falls in older people.
AB  - Nursing staff should check for signs or symptoms of fracture or potential for
      spinal injury before moving a patient following a fall. 

PMID- 25388703
TI  - Young carers get help and support through innovative pilot scheme.
AB  - A pioneering nurse is leading a pilot programme to tackle physical and mental
      health problems among young carers. 

PMID- 25388704
TI  - Healthcare workers advised to be honest and say sorry for mistakes.
AB  - Nurses and doctors might be afraid to admit their mistakes because they fear they
      will be disciplined, the Mid Staffs inquiry chair has warned. 

PMID- 25388705
TI  - RCN adds crosses in remembrance.
AB  - Outgoing RCN president Andrea Spyropoulos (left) and RCN student council member
      Claire Jeeves planted crosses at the Field of Remembrance at Westminster last
      week to honour all nurses who have died in times of conflict. 

PMID- 25388706
TI  - Withdrawal of goodwill--how to make the NHS sit up and listen.
AB  - It is often said that the NHS exists on the goodwill of its staff. 

PMID- 25388712
TI  - Heart attack.

PMID- 25388713
TI  - Exorcising the ghost of phantom limb.

PMID- 25388714
TI  - The best start.

PMID- 25388715
TI  - How empathy skills can change nursing.

PMID- 25388723
TI  - UN: Global Ebola Response.
AB  - The United Nations has been criticised for being slow to react to the latest
      Ebola outbreak in West Africa. But it is now making up for lost time with a
      concerted response to help the countries most affected. 

PMID- 25388726
TI  - The best of the week's health-related TV and radio.

PMID- 25388727
TI  - Neonatal Medicines Management UK app.

PMID- 25388728
TI  - Piecemeal approach could lead to confusion over industrial action.
AB  - Nurses and midwives will stage a four-hour strike as part of the ongoing pay
      dispute (News November 5). This will take place from 7am to 11am on Monday
      November 24. 

PMID- 25388729
TI  - International trade deal is 'the biggest threat to the NHS'.

PMID- 25388730
TI  - Union help for overseas nurses dealing with complex situations.

PMID- 25388732
TI  - Lack of leadership led to failures in care of patient with dementia.

PMID- 25388733
TI  - Use NMC checklist and guidance when applying to register.

PMID- 25388734
TI  - My father's end of life hospital care will haunt us for ever.

PMID- 25388735
TI  - Ray Rowden leaves the world a quieter, less colourful place.

PMID- 25388736
TI  - Developing nursing practice in platelet transfusions.
AB  - The number of platelet transfusions has risen steadily over the past five years.
      This article addresses some of the reasons for this increase and examines current
      transfusion practice in relation to findings of national audits of platelet use
      and current research. It explores the extended role of the nurse in platelet
      transfusions, including nurse authorisation, and presents an overview of
      education material available to inform practice and to ensure judicious use of
      platelet transfusions with maximum benefit for the patient. 

PMID- 25388737
TI  - Enhancing the clinical leadership of band 6 staff.
AB  - This is the third article in a series of seven articles on an initiative in NHS
      Lanarkshire. Visible clinical leaders can have a significant effect on patient
      care and standards of practice. Over the past decade the development of clinical
      leadership has focused on senior charge nurses or midwives and team leaders, that
      is, band 7 practitioners or above. Band 6 staff 'act up' in these roles and
      therefore need to develop the associated knowledge, skills and attributes for
      their current practice and future progression into such roles. This article
      reports on the establishment, implementation and evaluation of a clinical
      leadership programme developed specifically for band 6 nurses, midwives and
      allied health professionals at one Scottish NHS board. 

PMID- 25388738
TI  - Multiple sclerosis: managing a complex neurological disease.
AB  - This article describes the complex neurological condition multiple sclerosis (MS)
      and its management. It outlines the pathophysiology and symptoms, the importance
      of timely access to specialist services for treatment of symptoms, and relapse
      and disease management. New and emerging therapies for the management of MS, the
      role of the multidisciplinary team, the importance of holistic assessment and the
      role of the MS specialist nurse are discussed. Self-management of MS is integral
      to managing this life-limiting long-term condition. While there is no cure for
      MS, new and oral disease-modifying therapies providing better efficacy in
      stabilising the disease have recently been introduced, reducing relapse frequency
      and disease activity, and delaying the progression of disability. 

PMID- 25388739
TI  - Depression.
AB  - Depression is a common mental health disorder that impairs normal functioning,
      causes distress and has an adverse effect on an individual's quality of life. 

PMID- 25388740
TI  - Your career in a nutshell.
AB  - Most employers check out candidates online before offering a position to them so
      a personal website is an ideal opportunity to improve your odds of landing a
      dream job. 

PMID- 25388741
TI  - A well-deserved higher profile.
AB  - The Institute of Health Visiting (iHV) fellows programme is sponsored by the
      Department of Health. It acknowledges 150 health visitors invited to participate
      in a leadership programme. 

PMID- 25388743
TI  - The benefits of prioritisation.
AB  - Every day, dozens of tasks and challenges demand our attention. Along with
      patient care, nurses juggle administrative duties, keeping up to date with the
      latest evidence and regular continuing education. 

PMID- 25388744
TI  - Student life--Treasure the early days.
AB  - I can hardly believe that a year has passed since the nerves and the excitement
      of the first few weeks as a new nursing student. 

PMID- 25388745
TI  - [Me2C{SnCH(SiMe3)2}2]2. A MU-Me2C-bridged tetrastanna tetrahedrane.
AB  - A spacer-bridged bis(organostannylene) was obtained. In the solid-state it adopts
      the structure of a doubly-capped tetrahedron. It reacts with elemental oxygen,
      O2, giving tin suboxides. Additionally, the first solid state structure of a
      spacer-bridged diorgano tin dihydride is reported. 

PMID- 25388746
TI  - Erosive pustular dermatosis of the scalp associated with myelodysplastic
      syndrome.

PMID- 25388748
TI  - Genitalia-associated microbes in insects.
AB  - In sexual reproduction different types of symbiotic relationships between insects
      and microbes have become established. For example, some bacteria have evolved
      almost exclusive vertical transmission and even define the compatibility of
      insect mating partners. Many strictly sexually transmitted diseases have also
      been described in insects. Apart from such rather specific relationships the role
      of opportunistic infections in the reproductive process has been widely
      neglected. Opportunistic microbes transmitted passively during mating might
      impose an energetic cost, as the immune system will need to be alert and will use
      resources to fight potential intruders. Through mating wounds and contaminated
      reproductive organs opportunistic microbes might be transferred to mating
      partners and even enter the body cavity. Females as the "receiving" sex are
      particularly likely to have evolved adaptations to avoid or reduce opportunistic
      infections. Males of several species show highly complex seminal fluids, which as
      well as containing components that influence a males' fertilization success, also
      possess antimicrobial substances. The role of antimicrobials in the reproductive
      process is not well understood. Some evidence hints at the protection of sperm
      against microbes, indicating a role for natural selection in shaping the
      evolution of reproductive traits. By highlighting the potential importance of
      microbes in sexual selection and their role in reproduction in general I will
      make a case for studies in sexual selection, especially the ones investigating
      postcopulatory processes, that should incorporate environmental, as well as
      genotypic variation, in reproductive traits. 

PMID- 25388747
TI  - Vitamins and type 2 diabetes mellitus.
AB  - The present review evaluates the relationship between type 2 diabetes mellitus
      and individual or combined vitamins. Antioxidant vitamins A, C and E are found
      decreased in diabetic subjects, possibly due to an increased need to control the
      excessive oxidative stress produced by abnormalities in glucose metabolism. On
      the other hand, retinol binding protein exerts a modulating effect, as it has
      adipokine functions. With respect to the B group vitamins, thiamin, pyridoxine
      and biotin have been found decreased but the mechanisms are not clear, however
      supplementation has shown some improvement of the metabolic control in diabetic
      patients. The absorption of folic acid and vitamin B12 is importantly decreased
      by the prolongued use of metformin, which is the first choice drug in
      uncomplicated diabetes, thus these two nutrients have been found deficient in the
      disease and most probably need to be supplemented regularly. On the other hand,
      vitamin D is considered a risk factor for the development of diabetes as well as
      its complications, particularly cardiovascular ones. Although some studies have
      found an association of vitamin K intake with glucose metabolism further research
      is needed. Studies on the use of multivitamin supplements have shown unconclusive
      results. After reviewing the evidence, no real recommendation on the use of
      vitamin supplements in type 2 diabetes mellitus can be issued, however patients
      using metformin during prolongued periods may need folic acid and vitamin B12. 

PMID- 25388749
TI  - Non-linear relationship between birthweight and cardiometabolic risk factors in
      Chinese adolescents and adults.
AB  - AIM: To investigate the relationship between birthweight and cardiometabolic
      traits in two cohorts: one of Chinese adolescents and one of Chinese adults.
      METHODS: Birthweight and clinical data, including anthropometric traits, fasting
      plasma glucose and fasting plasma insulin levels, blood pressure and lipid
      profiles were collected from 2035 adolescents and 456 adults. A subset of 735
      subjects underwent an oral glucose tolerance test to measure the glucose and
      insulin concentrations at 0, 15, 30, 60 and 120 min. RESULTS: Among adolescents,
      birthweight showed U-shaped relationships with larger body size, obesity,
      abdominal obesity in girls, insulin resistance and worse lipid profiles (0.0013 <
      P(quadratic) < 0.0499), as well as an inverse association with fasting plasma
      glucose (P(linear) = 0.0368). After further adjustment for adiposity, decreasing
      birthweight was associated with elevated fasting plasma glucose levels, greater
      insulin resistance and worse lipid profiles (3.1 * 10-5 < P(linear) < 0.0058).
      Among adults, high birthweight was associated with larger body size and abdominal
      obesity in men, while low birthweight was associated with elevated glucose levels
      at 15, 30, 60 and 120 min and a greater area under the curve at 0-120 min, as
      well as with beta-cell dysfunction (6.5 * 10-5 < P(linear) < 0.0437). Adjustment
      for adult adiposity did not substantially change the relationships. There was
      significant interaction between birthweight and abdominal obesity in elevating
      fasting plasma insulin and homeostasis model assessment of insulin resistance (P
      > 0.05), with abdominally obese adolescents in the lowest birthweight category
      (<= 2.5 kg) having the highest risk of insulin resistance. CONCLUSIONS: Both high
      and low birthweights are associated with an increased risk of cardiometabolic
      abnormalities including obesity, abdominal obesity, hyperglycaemia, dyslipidaemia
      and insulin resistance, as well as with beta-cell dysfunction.

PMID- 25388751
TI  - Elevation of serum KL-6 levels during treatment with tumor necrosis factor-alpha
      inhibitor in patients with psoriasis.

PMID- 25388750
TI  - Antibiotic prescriptions and cycles of Mycoplasma pneumoniae infections in
      Norway: can a nationwide prescription register be used for surveillance?
AB  - Mycoplasma pneumoniae outbreaks cause increased use of macrolides and
      tetracyclines. We aimed to investigate whether drug use data, in addition to
      laboratory data, could improve understanding of the spread of M. pneumoniae
      epidemics. Number of users of Mycoplasma antibiotics (erythromycin, doxycycline,
      clarithromycin) per week and county of residence in an indicator age group (6-12
      years) was retrieved from the Norwegian prescription database for the epidemic
      season 2011-2012 and compared to non-epidemic seasons. In 2011, increased use of
      Mycoplasma antibiotics was first observed in September on the west coast of
      Norway. The Norwegian laboratory-based surveillance system showed the first
      increase in positive tests in August 2011 and an epidemic was announced on 25
      October 2011. At that time the use of Mycoplasma antibiotics had already exceeded
      three times the use in non-epidemic periods. Data for three counties from the
      regional microbiological laboratories showed that the increase in number of
      positive samples coincided in time with the increase in prescription data.
      Laboratory data cannot accurately determine the extent of an epidemic, and drug
      use data cannot identify the cause. Establishing a systematic interaction between
      the two monitoring systems will enhance surveillance and probably contribute to
      improved infection control and prudent antibiotic prescribing. 

PMID- 25388752
TI  - Mealtime behaviors and food consumption of perceived picky and nonpicky eaters
      through home use test.
AB  - Picky eating has been investigated through numerous surveys and food recalls, but
      few studies have applied in-home meal evaluations as a method to investigate
      behaviors and food preferences of children perceived by their parent to be a
      picky eater (PE) or nonpicky eater (NPE). A 2-wk in-home meal study was completed
      to investigate differences in PE and NPE mealtime behaviors and food selections
      using real-time parental observations. Parents (n = 170) and their 2- to 4-y-old
      children (83 PE and 87 NPE) evaluated 5 standardized meals in-home. Parents
      recorded their child's and their own hedonic liking of the products and completed
      an assessment of their child's behavior and consumption at each meal. Significant
      differences were found between perceived PE and NPE children for all 16 behaviors
      assessed. On average, perceived NPE were assessed to consume a higher percentage
      of the meal served and to have higher acceptance scores for most of the foods
      evaluated. Some foods, though, like breaded chicken and plain pasta, were liked
      equally by PE and NPE. Several significant differences in hedonic liking were
      revealed when PE children were compared to their parents. Yet, few differences in
      liking occurred between NPE children and their parents or between the 2 parental
      groups. Because study participants evaluated meals real-time rather than memory
      recall, the differences and similarities found between perceived PE and NPE may
      be considered direct experiential evidence with reduced subjective bias as
      created when subjects recall past experiences. Thus, findings from this study can
      provide the foundation to establish an objective definition and classification of
      PE and NPE. 

PMID- 25388753
TI  - Molecular and morphological evidence for three species of Diplostomum (Digenea:
      Diplostomidae), parasites of fishes and fish-eating birds in Spain.
AB  - BACKGROUND: Recent molecular studies have revealed high species diversity of
      Diplostomum in central and northern Europe. However, our knowledge of the
      distribution of Diplostomum spp. in the southern distributional range in Europe
      of the snail intermediate hosts (Lymnaea stagnalis and Radix spp.) is rather
      limited. This study aims to fill this gap in our knowledge using molecular and
      morphological evidence. METHODS: Nineteen fish species and six fish-eating bird
      species were sampled opportunistically in three regions (Catalonia, Extremadura
      and Aragon) in Spain. All isolates of Diplostomum spp. were characterised
      morphologically and molecularly. Partial sequences of the barcode region of the
      cox1 mitochondrial gene and complete sequences of the ribosomal ITS1-5.8S-ITS2
      gene cluster were used for molecular identification of the isolates. RESULTS:
      Integrated morphological and molecular analyses demonstrated the presence of
      three species among the larval and adult isolates of Diplostomum spp. sampled in
      Spain: Diplostomum spathaceum (in fish and birds), D. pseudospathaceum (in birds)
      and Diplostomum sp. (in fish) referred to as Clade Q sensu Georgieva et al. (Int
      J Parasitol, 43:57-72, 2013). We detected ten cox1 haplotypes among the isolates
      of D. spathaceum with only one haplotype shared with adult isolates from central
      and northern Europe. No specific geographic pattern of the distribution of the
      novel haplotypes was found. CONCLUSION: This first molecular exploration of the
      diversity of Diplostomum spp. in southern Europe indicates much lower species
      richness compared with the northern regions of Europe.

PMID- 25388754
TI  - The role of nitric oxide and oxidative stress in intestinal damage induced by
      selenium deficiency in chickens.
AB  - Nitric oxide (NO) is an essential messenger molecule and is associated with
      inflammation and oxidative stress. Although NO has important biological functions
      in mammals, its role in the mechanism that occurs after intestinal injuries in
      chickens remains unknown. The objective of the present study was to investigate
      the real role of NO and oxidative stress in the intestinal injuries of chickens
      induced by selenium (Se) deficiency. A total 150 chickens were randomly divided
      into the following two groups: a low-Se group (L group, fed a Se-deficient diet
      containing 0.020 mg/kg Se) and a control group (C group, fed a commercial diet
      containing 0.2 mg/kg Se). The activities and mRNA levels of glutathione
      peroxidase (GSH-Px), the production of glutathione (GSH) and NO, and the protein
      and mRNA levels of inducible nitric oxide synthase (iNOS) were examined in the
      intestinal tissues (duodenum, jejunum, and rectum) at 15, 25, 35, 45, and 55
      days. Methane dicarboxylic aldehyde (MDA) levels were also detected by assay
      kits. Then, the morphologies of the tissues were observed under the microscope
      after hematoxylin and eosin staining (H&E staining). The results showed that Se
      deficiency induced higher inflammatory damage and MDA levels (P < 0.05), which
      were accompanied by higher levels of iNOS and NO but lower levels of GSH and GSH
      Px (P < 0.05). Our results indicated that Se deficiency induced oxidative damage
      in the intestinal tracts of chickens and that low levels of GSH-Px and high
      contents of NO may exert a major role in the injury of the intestinal tract
      induced by Se deficiency. 

PMID- 25388755
TI  - The influence of physical activity on hair toxic and essential trace element
      content in male and female students.
AB  - The primary aim of the current study is to estimate the effect of different
      physical activity levels on hair trace element content in male and female
      students. A total of 113 students (59 women and 54 men) of P. G. Demidov
      Yaroslavl State University (Yaroslavl, Russia) took part in the current
      investigation. According to the level of the physical activity, all students were
      divided into three groups: high, medium, and low physical activity. Essential and
      toxic metal content (MUg/g) in hair samples was assessed by inductively coupled
      plasma mass spectrometry using NexION 300D + NWR213 (Perkin-Elmer, USA). The
      obtained data show that hair iodine, zinc, arsenic, nickel, and tin levels are
      not related to physical activity in male and female students. At the same time,
      increased physical activity is associated with decreased hair copper, vanadium,
      bismuth, and mercury content in comparison to the low physical activity groups.
      Students with higher physical activity are also characterized by significantly
      higher hair cobalt, iron, manganese, selenium, cadmium, lithium, and lead
      concentrations. Finally, statistical analysis has revealed maximal gender
      differences in hair trace element content in the high physical activity groups,
      whereas in the low activity groups, the hair metal concentrations were nearly
      similar in females and males. 

PMID- 25388756
TI  - Effect of additional chromium supplementation on health status, metabolic
      responses, and performance traits in periparturient Murrah Buffaloes (Bubalus
      bubalis).
AB  - This study was conducted to determine the effects of inorganic chromium (Cr) on
      body condition, metabolic responses, lactation performance, and reproductive
      parameters in periparturient Murrah buffaloes. Twenty-four multiparous advanced
      pregnant Murrah buffaloes were randomly assigned to four treatment diets. Feeding
      regimen was the same in all the groups, except that the animals in the four
      respective groups were additionally supplemented with 0.0, 0.5, 1.0, and 1.5 mg
      of Cr/kg dry matter (DM) from day 60 prepartum to 150 days postpartum. Dry matter
      intake (DMI) and milk production were recorded every day, while body condition
      score (BCS) and whole blood samples were collected at days -60, -45, -30, -15, 
      7, -3, 0, 3, 7, 15, 30, 45, 60, 90, 120, and 150 relative to actual calving. As
      the days to calving advanced, DMI, plasma glucose, insulin, leptin, and Cr levels
      decreased (P < 0.05), and the levels were minimum on the day of calving. In
      contrast, the concentration of nonesterified fatty acid (NEFA) increased (P <
      0.05) and was found to be highest at parturition. No change in DMI as well as BCS
      was observed due to dietary treatments. Supplementation of Cr improved plasma
      concentration of glucose, leptin, and Cr levels. However, the concentration of
      insulin decreased (P < 0.05) with the increased level of supplemental Cr. Milk
      yield (kg/day) was improved significantly (P < 0.05) in groups supplemented with
      1.0 or 1.5 mg Cr/DM; however, only a small change was recorded in the group fed
      0.5 mg Cr/kg DM. Fat-corrected milk and energy-corrected milk were 28.78 and
      42.32 % and 28.76 and 41.68 % higher in the 1.0 and 1.5 mg Cr/DM groups,
      respectively. Dietary Cr supplementation during the peripartum period had
      beneficial effects on the reproductive performance of buffaloes. These results
      could be interpreted as an improvement in the body condition, metabolic response,
      milk yield, efficiency of milk production and nutrient utilization, and
      reproductive performance of peripartum Murrah buffaloes. 

PMID- 25388757
TI  - Estimation of cultivable bacterial diversity in the cloacae and pharynx in
      Eurasian griffon vultures (Gyps fulvus).
AB  - In this work, we describe the biodiversity of cloacal and pharynx culture-based
      bacteria (commensal and pathogenic), in 75 Eurasian griffon vultures (Gyps
      fulvus) from two geographic areas. We address the question of whether the
      cultivable microbiota of vultures is organised into assemblages occurring by
      chance. In addition, we assess bacterial diversity in both anatomic regions and
      geographic areas. Bacterial diversity was represented by 26 Gram-negative and 20
      Gram-positive genera. The most common genera were Escherichia, Enterococcus,
      Staphylococcus, Clostridium and Lactococcus. Escherichia coli and Enterococcus
      faecalis were the most common species in cloacal and pharyngeal samples.
      Staphylococcus and Erysipelothrix were isolated from the pharynx and Salmonella
      and Corynebacterium from the cloacae, and no Campylobacter was isolated from the
      cloacal swabs. Ten cloacal swabs were positive for Salmonella, of which five
      isolates were Salmonella enterica serotype 4,(5),12:i:-, one isolate was S.
      enterica serotype Derby, three isolates were S. enterica serotype 61:k:1,5,7 and
      one isolate was S. enterica serotype Infantis. The null modelling approach
      revealed that the commensal bacteria of vultures are not structured in
      assemblages. On the other hand, differences in bacterial genus and species
      richness between cloacal and pharyngeal samples or between geographic areas were
      clear, with the pharynx in vultures from both geographic areas being richer. The
      results of this study indicate also that vultures can serve as a reservoir of
      certain pathogenic zoonotic bacteria. The dissemination of these zoonotic
      pathogens in wildlife could be prevented by periodic sanitary surveys. 

PMID- 25388758
TI  - Low-potential respirators support electricity production in microbial fuel cells.
AB  - In this paper, we analyse how electric power production in microbial fuel cells
      (MFCs) depends on the composition of the anodic biofilm in terms of metabolic
      capabilities of identified sets of species. MFCs are a promising technology for
      organic waste treatment and sustainable bioelectricity production. Inoculated
      with natural communities, they present a complex microbial ecosystem with
      syntrophic interactions between microbes with different metabolic capabilities.
      Our results demonstrate that low-potential anaerobic respirators--that is those
      that are able to use terminal electron acceptors with a low redox potential--are
      important for good power production. Our results also confirm that community
      metabolism in MFCs with natural inoculum and fermentable feedstock is a two-stage
      system with fermentation followed by anode respiration.

PMID- 25388759
TI  - Hormesis effects of amoxicillin on growth and cellular biosynthesis of
      Microcystis aeruginosa at different nitrogen levels.
AB  - Coexisting antibiotic contaminants have potential to regulate cyanobacterial
      bloom, and the regulation is likely affected by nitrogen supply. A typical
      cyanobaterium Microcystis aeruginosa was cultured with 0.05-50 mg L(-1) of
      nitrogen and exposed to 100-600 ng L(-1) of amoxicillin for 7 days. Algal growth
      was not significantly (p > 0.05) affected by amoxicillin at the lowest nitrogen
      level of 0.05 mg L(-1), stimulated by 600 ng L(-1) of amoxicillin at a moderate
      nitrogen level of 0.5 mg L(-1) and enhanced by 100-600 ng L(-1) of amoxicillin at
      higher nitrogen levels of 5-50 mg L(-1). Amoxicillin affected chlorophyll-a, psbA
      gene, and rbcL gene in a similar manner as algal growth, suggesting a regulation
      of algal growth via the photosynthesis system. At each nitrogen level, synthesis
      of protein and polysaccharides as well as production and release of microcystins
      (MCs) increased in response to environmental stress caused by amoxicillin.
      Expression of ntcA and mcyB showed a positive correlation with the total content
      of MCs under exposure to amoxicillin at nitrogen levels of 0.05-50 mg L(-1).
      Nitrogen and amoxicillin significantly (p < 0.05) interact with each other on the
      regulation of algal growth, synthesis of chlorophyll-a, production and release of
      MCs, and expression of ntcA and mcyB. The nitrogen-dependent stimulation effect
      of coexisting amoxicillin contaminant on M. aeruginosa bloom should be fully
      considered during the combined pollution control of M. aeruginosa and
      amoxicillin. 

PMID- 25388760
TI  - Noninfectious Diarrhea in HIV Seropositive Individuals: a Review of Prevalence
      Rates, Etiology, and Management in the Era of Combination Antiretroviral Therapy.
AB  - INTRODUCTION: Diarrhea poses a substantial burden for patients with human
      immunodeficiency virus (HIV), negatively impacting quality-of-life (QoL) and
      adherence to antiretroviral therapy. During the combination antiretroviral
      therapy (cART) era, as incidence of opportunistic infection as a cause of
      diarrhea decreased, incidence of noninfectious diarrhea (including diarrhea as an
      adverse event [AE] of cART and HIV enteropathy) increased proportionately. A
      literature search was conducted for information on prevalence, etiology, and
      treatment options for noninfectious diarrhea in patients with HIV. RESULTS: For
      marketed antiretroviral therapies, up to 28% of patients live with >4 loose or
      watery stools per day. The US Food and Drug Administration (FDA) does not require
      pharmaceutical manufacturers to include, within approved prescribing information,
      prevalence rates for all grades of diarrhea. Traditionally, noninfectious
      diarrhea management focused on avoiding use of diarrhea-associated cART; symptom
      management (nonpharmacologic and/or pharmacologic); and, as a last resort,
      changing cART. Examining the evidence upon which this approach is based reveals
      that most strategies rely upon anecdotal information and case reports. This
      review summarizes the literature and updates clinicians on the most recent
      options for management of noninfectious diarrhea in patients with HIV.
      CONCLUSION: Diarrhea in patients with HIV is a significant unmet clinical need
      that contributes to worsening QoL and complicates medical management. Approaching
      management using a stepwise method of nonpharmacologic (diet), nonprescription
      (over-the-counter) and, finally, prescription agent changes (modification of cART
      or addition of an evidence-based antidiarrheal) appears reasonable, despite a
      lack of clear scientific evidence to support the initial two steps of this
      approach. If diet modifications, including psyllium and fiber introduction, fail
      to resolve noninfectious diarrhea in patients with HIV, loperamide followed by
      crofelemer should be considered. Clinicians are encouraged to review the most
      recent literature, not rely upon prescribing information. Continued vigilance by
      HIV providers to the presence of gastrointestinal AEs, even in patients taking
      the most recently approved antiretroviral agents, is warranted. Additional
      research is justified in identifying the etiology and management of HIV
      associated diarrhea in patients on successful cART regimens.

PMID- 25388761
TI  - [Moebius syndrome and narcolepsy].
AB  - BACKGROUND: Moebius syndrome is a rare neurological disease that has a frequent
      association with parasomnia. CASE REPORT: We report on a patient with Moebius
      syndrome and the clinical presentation of a narcolepsy cataplexy syndrome. With
      the hypoplasia of the brainstem in the cranial magnetic resonance imaging, we
      were able to show the morphological correlate of Moebius syndrome. Comorbidity
      was detected by cognitive tests, polysomnography and detection of hypocretin in
      the cerebrospinal fluid. Despite normal sleep onset latency and only one episode
      of sleep onset rapid eye movement (REM) in the multiple sleep latency test, where
      expressiveness is significantly reduced in cases of paralysis of horizontal eye
      movement, the diagnosis of parasomnia with narcolepsy cataplexy symptoms could be
      made. DISCUSSION: The hypocretin level of 132 pg/ml measured in the cerebro
      spinal fluid is compatible with this diagnosis and shows the relevance of a
      detailed diagnostic of parasomnia in patients with Moebius syndrome.

PMID- 25388762
TI  - Role of p38 MAPK in enhanced human cancer cells killing by the combination of
      aspirin and ABT-737.
AB  - Regular use of aspirin after diagnosis is associated with longer survival among
      patients with mutated-PIK3CA colorectal cancer, but not among patients with wild
      type PIK3CA cancer. In this study, we showed that clinically achievable
      concentrations of aspirin and ABT-737 in combination could induce a synergistic
      growth arrest in several human PIK3CA wild-type cancer cells. In addition, our
      results also demonstrated that long-term combination treatment with aspirin and
      ABT-737 could synergistically induce apoptosis both in A549 and H1299 cells. In
      the meanwhile, short-term aspirin plus ABT-737 combination treatment induced a
      greater autophagic response than did either drug alone and the combination
      induced autophagy switched from a cytoprotective signal to a death-promoting
      signal. Furthermore, we showed that p38 acted as a switch between two different
      types of cell death (autophagy and apoptosis) induced by aspirin plus ABT-737.
      Moreover, the increased anti-cancer efficacy of aspirin combined with ABT-737 was
      further validated in a human lung cancer A549 xenograft model. We hope that this
      synergy may contribute to failure of aspirin cancer therapy and ultimately lead
      to efficacious regimens for cancer therapy. 

PMID- 25388763
TI  - Intra-operative assessment of pulmonary artery pressure by transoesophageal
      echocardiography.
AB  - The clinical value of the estimation of systolic pulmonary artery pressure, based
      on Doppler assessment of peak tricuspid regurgitant velocity using
      transoesophageal echocardiography, is unclear. We studied 109 patients to
      evaluate the feasibility of obtaining adequate Doppler recordings, and compared
      Doppler estimates with values measured using a pulmonary artery catheter in a
      subset of 33 patients. Tricuspid regurgitation was evaluated at the mid
      oesophageal level at 0-120 degrees  using Doppler echocardiography. A Doppler
      signal was defined as adequate if there was a <= 20 degrees  alignment and a full
      envelope. Doppler estimates of systolic pulmonary artery pressure within 10 mmHg
      and 15% of the value recorded with the pulmonary artery catheter were considered
      to be in sufficient agreement. Adequate Doppler signals were obtained in 64/109
      (59%) patients before and 54/103 (52%) after surgery. Doppler estimates by
      transoesophageal echocardiography were within 10 mmHg and 15% of values recorded
      with the pulmonary artery catheter in 28/33 (75%) patients and 22/31 (55%)
      patients, respectively. In 7 (21%) patients, the echocardiographic Doppler
      measurement exceeded the measured systolic pulmonary artery pressure by more than
      30%. Our study indicates that estimation of the systolic pulmonary artery
      pressure using transoesophageal Doppler echocardiography is not a reliable and
      clinically useful method in anaesthetised patients undergoing mechanical
      ventilation. 

PMID- 25388764
TI  - Modeling energy intake by adding homeostatic feedback and drug intervention.
AB  - Energy intake (EI) is a pivotal biomarker used in quantification approaches to
      metabolic disease processes such as obesity, diabetes, and growth disorders.
      Eating behavior is however under both short-term and long-term control. This
      control system manifests itself as tolerance and rebound phenomena in EI, when
      challenged by drug treatment or diet restriction. The paper describes a model
      with the capability to capture physiological counter-regulatory feedback actions
      triggered by energy imbalances. This feedback is general as it handles tolerance
      to both increases and decreases in EI, and works in both acute and chronic
      settings. A drug mechanism function inhibits (or stimulates) EI. The deviation of
      EI relative to a reference level (set-point) serves as input to a non-linear
      appetite control signal which in turn impacts EI in parallel to the drug
      intervention. Three examples demonstrate the potential usefulness of the model in
      both acute and chronic dosing situations. The model shifts the predicted
      concentration-response relationship rightwardly at lower concentrations, in
      contrast to models that do not handle functional adaptation. A fourth example
      further shows that the model may qualitatively explain differences in rate and
      extent of adaptation in observed EI and its concomitants in both rodents and
      humans. 

PMID- 25388765
TI  - Comparative efficacy of a herbal and a non-herbal dentifrice on dentinal
      hypersensitivity: a randomized, controlled clinical trial.
AB  - AIM: Dentinal hypersensitivity (DH) is a common painful condition of the teeth of
      adults. The present study was conducted to assess and compare the efficacy of a
      commercially-available novel herbal dentifrice with a non-herbal potassium
      nitrate in the reduction of DH. METHODS: A total of 145 individuals (73 males and
      72 females; aged 25-60 years) were divided into three groups randomly: (a) group
      1: a placebo dentifrice; (b) group 2: a commercially-available herbal dentifrice;
      and (c) group 3: 5% non-herbal potassium nitrate. The sensitivity scores for
      controlled air stimulus and cold water were recorded at baseline, 6 weeks, and 12
      weeks. RESULTS: Both groups 2 and 3 were found to be significantly better, as
      compared to the placebo group at the end of 6 and 12 weeks in the reduction of
      DH. Group 2 also showed comparable results in the reduction of DH when compared
      to group 3. CONCLUSION: The herbal dentifrice showed comparable results to the
      non-herbal dentifrice and can be recommended for the treatment of DH.

PMID- 25388766
TI  - Enhanced second-harmonic generation from metal-integrated semiconductor nanowires
      via highly confined whispering gallery modes.
AB  - Coherent and tunable nanoscale light sources utilizing optical nonlinearities are
      required for applications ranging from imaging and bio-sensing to on-chip all
      optical signal processing. However, owing to their small sizes, the efficiency of
      nanostructures even with high nonlinear coefficients is poor, therefore requiring
      very high excitation energies. Although surface-plasmon resonances of metal
      nanostructures can enhance surface nonlinear processes such as second-harmonic
      generation, they still suffer from low conversion efficiencies owing to their
      intrinsically low nonlinear coefficients. Here we show highly enhanced and
      directional second-harmonic generation from individual CdS nanowires integrated
      with silver nanocavities (>1,000 times higher external efficiency compared with
      bare CdS), in which the lowest-order whispering gallery mode is engineered to
      concentrate light in the nonlinear material while minimizing Ohmic losses. The
      directional nonlinear signal is redirected into another waveguide, which is then
      utilized to configure an optical router that can potentially serve as a tunable
      coherent light source to enable on-chip signal processing for integrated
      nanophotonic systems. 

PMID- 25388767
TI  - Structural heterogeneity of milk casein micelles: a SANS contrast variation
      study.
AB  - We examine the internal structure of milk casein micelles using the contrast
      variation method in Small-Angle Neutron Scattering (SANS). Experiments were
      performed with casein dispersions of different origins (i.e., milk powder or
      fresh milk) and extended to very low q-values (~9 * 10(-4) A(-1)), thus making it
      possible to precisely determine the apparent gyration radius Rg at each contrast.
      From the variation of I(q -> 0) with contrast, we determine the distribution of
      composition of all the particles in the dispersions. As expected, most of these
      particles are micelles, made of casein and calcium phosphate, with a narrow
      distribution in compositions. These micelles always coexist with a very small
      fraction of fat droplets, with sizes in the range of 20-400 nm. For the
      dispersions prepared from fresh milk, which were purified under particularly
      stringent conditions, the number ratio of fat droplets to casein micelles is as
      low as 1 to 10(6). In that case, we are able to subtract from the total intensity
      the contribution of the fat droplets and in this way obtain the contribution of
      the micelles only. We then analyze the variation of this contribution with
      contrast using the approach pioneered by H. B. Stuhrmann. We model the casein
      micelle as a core-shell spherical object, in which the local scattering length
      density is determined by the ratio of calcium phosphate nanoclusters to proteins.
      We find that models in which the shell has a lower concentration of calcium
      phosphate than the core give a better agreement than models in which the shell
      has a higher density than the core. 

PMID- 25388769
TI  - Family structure and eating behavior disorders.
AB  - INTRODUCTION: The modern way of life, characterized by the cult of individualism,
      discredited authority, and a proliferation of points of view about reality, has
      modified family structure. This social structure imbues families and the way that
      its members become ill, in such a way that eating behavior disorders (EDs) have
      become a typically postmodern way of becoming ill. METHODOLOGY: The aim is to
      understand the systemic structure and vulnerability of families by comparing 108
      families with members who have ED to 108 families without pathology. A
      questionnaire administered by an interview with trained personnel was used.
      RESULTS: Families with ED have a different structure from the families in the
      control group. They have more psychiatric history and poor coping skills. The
      family hierarchy is not clearly defined and the leadership is diffuse, with
      strict and unpredictable rules, more intergenerational coalitions, and fewer
      alliances. The relationship between the parents is distant or confrontational,
      and their attitudes towards their children are complacent and selfish, with
      ambivalent and unaffectionate bonds. In the case of mothers, this is manifested
      by separation anxiety and dyadic dependence. Their expectations concerning their
      offspring are either very demanding and unrealistic, or indifferent, and there is
      less control of their behavior, in addition to poor organization of the family
      meals. CONCLUSIONS: The structural differences between the two groups of families
      seem to be important for the occurrence and maintenance of EDs, although they may
      not be the only cause. The results suggest strategies for clinical intervention
      in EDs.

PMID- 25388768
TI  - A hybrid NMR/SAXS-based approach for discriminating oligomeric protein interfaces
      using Rosetta.
AB  - Oligomeric proteins are important targets for structure determination in
      solution. While in most cases the fold of individual subunits can be determined
      experimentally, or predicted by homology-based methods, protein-protein
      interfaces are challenging to determine de novo using conventional NMR structure
      determination protocols. Here we focus on a member of the bet-V1 superfamily,
      Aha1 from Colwellia psychrerythraea. This family displays a broad range of
      crystallographic interfaces none of which can be reconciled with the NMR and SAXS
      data collected for Aha1. Unlike conventional methods relying on a dense network
      of experimental restraints, the sparse data are used to limit conformational
      search during optimization of a physically realistic energy function. This work
      highlights a new approach for studying minor conformational changes due to
      structural plasticity within a single dimeric interface in solution.

PMID- 25388770
TI  - Use of health care resources and loss of productivity in patients with depressive
      disorders seen in Primary Care: INTERDEP Study.
AB  - INTRODUCTION: The InterDep Study analyzes the characteristics of patients with a
      depressive disorder who, in the last years, have received health services at
      Primary Care in an specific health care area. The InterDep Study evaluates the
      use of heath care resources attributable to depression (direct costs) and loss of
      productivity (indirect costs). It also analyzes these patients' referral to the
      specialist. METHODS: A retrospective, multicenter observational study was
      conducted using computerized medical records collected in an anonymized database
      of 22,795 patients who received health care services between 2005 and 2009 for a
      new episode of depressive disorder in a specific Primary Care Area of the Madrid
      Health Service (Community of Madrid) (former Area 6). RESULTS: A 74.5% of the
      patients with depressive disorders were women, mean age 54 years (SD 17.7).
      According to the ICPC classification, depression was the most frequently
      diagnosed disorder (48.4%), followed by anxiety (35.4%) and adjustment disorder
      (16.2%). A 88.5% were treated with selective serotonin reuptake inhibitors
      (SSRIs) (N06AB). The average total annual cost (both direct and indirect costs)
      was 725.2 Euros. Loss of productivity was the major cost in depressed patients
      treated in primary care (501.0 Euros), especially among those patients on
      disability. A 29.7% of the patients were referred to specialized care.
      CONCLUSIONS: The prevalence and the socio-sanitary impact of depressive disorders
      in primary care require adequate clinical competence from the physician to
      guarantee proper disease management thus, minimizing the significant direct
      (health care resources) and indirect (loss of productivity) cost.

PMID- 25388771
TI  - Psychometric properties of Spanish version of QIDS-SR16 in depressive patients.
AB  - INTRODUCTION: Depression is a worldwide health problem. Thus, making the
      diagnosis with reliable and short tests is crucial. In this regard, the Quick
      Inventory of Depressive Symptomatology-Self Report (QIDS-SR16) has been validated
      in several countries. It was found that this instrument has a correct balance
      between time and reliability. This study has aimed to assess psychometric
      properties of QIDS-SR16 Spanish version, and to calculate several cutoffs to
      evaluate the depressive disorder severity. METHOD: The study was based on the
      data from the RESIST study that recruited 1595 depressive patients from 17
      regional communities. Instruments used were Hamilton Depression Rating Scale
      (HDRS17) and Spanish version of QIDS-SR16. Statistical analyses included test
      retest reliability and internal consistency calculation, and exploratory factor
      analysis. In addition, ROC curve was calculated in order to determine different
      cutoff values. RESULTS: QIDS-SR16 shows adequate test-retest reliability and high
      internal consistency (alpha=0.871), as well as ROC value of 0.946. Exploratory
      factor analysis showed a one factor model, which accounted for 46.80% of
      variance. Convergent validity and sensitivity to change were adequate.
      DISCUSSION: The results suggest that the QIDS-SR16 is a reliable test to assess
      depressive symptom severity in the Spanish population. The cutoff that shows the
      best sensitivity/specificity rate was a total score of 7.

PMID- 25388772
TI  - Interventions for caregivers of patients with dementia.
AB  - INTRODUCTION: With the aging of the population, an increasing number of people
      have dementia, most of whom are receiving home care. Caregivers are exposed to a
      variety of stressors, which may lead to feeling burdened, or to depression and
      anxiety. Various programs or structured interventions have been developed to
      prevent or lessen these negative consequences. The efficacy of these
      interventions is debated, mainly due to methodological differences between
      studies. Review studies so far have presented important discrepancies, thus
      perpetuating a lack of clarity regarding this important geriatric care problem.
      The effectiveness of interventions designed to prevent or reduce the burden
      and/or symptoms of anxiety and depression in informal caregivers are reviewed
      precisely and rigorously. METHODS: A systematic review of randomized controlled
      studies assessing the efficacy of structured interventions on the variables of
      burden, depression and anxiety in informal caregivers of patients with dementia.
      RESULTS: The literature search yielded 997 references, of which 35 met the
      screening criteria. Of these studies, 51.4% had results that were statistically
      favorable to intervention. The methodology used varied widely between studies.
      CONCLUSIONS: Overall, the available evidence favors the implementation of
      structured intervention programs, although the results are heterogeneous.
      Psychoeducational interventions yield better results and can be better adapted to
      the needs of caregivers.

PMID- 25388773
TI  - Treatment guidelines for Attention Deficit and Hyperactivity Disorder: A critical
      review.
AB  - A series of clinical guidelines for Attention Deficit and Hyperactivity Disorder
      throughout life have been published in recent years. The aim is to provide a
      synthesis of the best available scientific knowledge and facilitate clinical work
      as well as to make a critical review of the latest clinical guidelines based on
      treatment and recommendations. Searches of the following databases were
      performed: MEDLINE/ PubMed/ Index Medicus, PsycINFO/ PsyLIT and the Science
      Citation Index at Web of Science (ISI). The indexed MeSH terms
      &#8220;ADHD,&#8221; &#8220;guideline,&#8221; &#8220;therapeutics&#8221; were used
      for the search, and a total of 10 articles and 9 guides were selected. The
      guidelines indicate that the diagnosis of ADHD is made by clinical assessment and
      must be performed by a health professional with training and experience in the
      disorder. Multimodal treatment is ideal for the integral management of ADHD.
      Pharmacotherapy remains the first choice treatment for ADHD throughout life,
      particularly stimulant medication and among them, highlighting treatment with
      methylphenidate and all guidelines agree that psychological therapy increases the
      effectiveness of treatment as co-adjuncts to pharmacotherapy. 

PMID- 25388774
TI  - Apropos of a case: relationship of ischemic colitis with clozapine.

PMID- 25388776
TI  - Effect of enzyme replacement therapy in late onset Pompe disease: open pilot
      study of 48 weeks follow-up.
AB  - Late-onset Pompe disease (LOPD) is an autosomal recessive disorder caused by
      deficiency of the enzyme acid glucosidase alfa (GAA). Recently, enzyme
      replacement therapy (ERT) using recombinant human GAA (rhGAA) became clinically
      available, and is expected to modify the clinical course in LOPD of various
      stages. In this study, we evaluated the efficacy and adverse events of ERT for 48
      weeks in Korean LOPD patients. Five Korean LOPD patients were included in the
      study. At baseline, clinical and laboratory features, including muscular and
      pulmonary function, were assessed, and rhGAA was infused every 2 weeks. Then,
      patients were examined at every 12-week interval for evaluation of changes in
      motor and pulmonary function for 48 weeks along with adverse reactions to ERT.
      The muscular and pulmonary function of the patients varied depending on the
      baseline condition of the patient after 48 weeks of ERT. However, the overall
      function of the patients showed stabilization of the disease rather than the
      improvement seen in infantile-onset Pompe disease. This is the first clinical
      study on ERT of Korean LOPD patients. Results of our study showed stabilization
      of muscular and pulmonary function in LOPD patients for 48 weeks with a favorable
      prognosis for patients who received early diagnosis and ambulatory patients. One
      of our patients developed a serious anaphylactic reaction, which necessitated the
      cessation of further ERT. Therefore, our study shows that early diagnosis and ERT
      are important in preventing further deterioration of the disease.

PMID- 25388775
TI  - Where have all the tadpoles gone? Individual genetic tracking of amphibian larvae
      until adulthood.
AB  - Reliably marking larvae and reidentifying them after metamorphosis is a challenge
      that has hampered studies on recruitment, dispersal, migration and survivorship
      of amphibians for a long time, as conventional tags are not reliably retained
      through metamorphosis. Molecular methods allow unique genetic fingerprints to be
      established for individuals. Although microsatellite markers have successfully
      been applied in mark-recapture studies on several animal species, they have never
      been previously used in amphibians to follow individuals across different life
      cycle stages. Here, we evaluate microsatellites for genetic across-stages mark
      recapture studies in amphibians and test the suitability of available software
      packages for genotype matching. We sampled tadpoles of the dendrobatid frog
      Allobates femoralis, which we introduced on a river island in the Nature Reserve
      'Les Nouragues' in French Guiana. In two subsequent recapture sessions, we
      searched for surviving juveniles and adults, respectively. All individuals were
      genotyped at 14 highly variable microsatellite loci, which yielded unique genetic
      fingerprints for all individuals. We found large differences in the
      identification success of the programs tested. The pairwise-relatedness-based
      approach, conducted with the programs kingroup or ML-Relate, performed best with
      our data set. Matching ventral patterns of juveniles and adult individuals acted
      as a control for the reliability of the genetic identification. Our results
      demonstrate that microsatellite markers are a highly powerful tool for studying
      amphibian populations on an individual basis. The ability to individually track
      amphibian tadpoles throughout metamorphosis until adulthood will be of
      substantial value for future studies on amphibian population ecology and
      evolution. 

PMID- 25388777
TI  - The epidemiology of alcohol consumption and multiple sclerosis: a review.
AB  - Alcohol consumption is accounted for a large proportion in patients with multiple
      sclerosis (MS) and may be a modifiable lifestyle factor that affects the risk of
      developing the disease. The epidemiological studies about the association between
      MS and alcohol consumption have got corresponding studies during the last decade.
      It has been suggested that alcohol consumption was associated with mood
      disorders, disability and even onset of MS, but a common theme is lacking. To
      make an understanding of the effect of alcohol consumption on MS, the related
      epidemiological evidence and potential mechanisms are reviewed.

PMID- 25388778
TI  - Adaptive common average filtering for myocontrol applications.
AB  - The use of electromyography (EMG) for the control of upper-limb prostheses has
      received great interest in neurorehabilitation engineering since decades.
      Important advances have been performed in the development of machine learning
      algorithms for myocontrol. This paper describes a novel adaptive filter for EMG
      preprocessing to be applied as conditioning stage for optimal subsequent
      information extraction. The aim of this filter is to improve both the quality
      (signal-to-noise ratio) and the selectivity of the EMG recordings. The filter is
      based on the classic common average reference (CAR), often used in EEG
      processing. However, while CAR is stationary, the proposed filter, which is
      referred to as adaptive common average reference (ACAR), is signal-dependent and
      its spatial transfer function is adapted over time. The ACAR filter is evaluated
      in this study for noise reduction and selectivity. Furthermore, it is proven that
      its application improves the performance of both pattern recognition and
      regression methods for myoelectric control. It is concluded that the proposed
      novel filter for EMG conditioning is a useful preprocessing tool in myocontrol
      applications. 

PMID- 25388779
TI  - Directional dual-tree complex wavelet packet transforms for processing quadrature
      signals.
AB  - Quadrature signals containing in-phase and quadrature-phase components are used
      in many signal processing applications in every field of science and engineering.
      Specifically, Doppler ultrasound systems used to evaluate cardiovascular
      disorders noninvasively also result in quadrature format signals. In order to
      obtain directional blood flow information, the quadrature outputs have to be
      preprocessed using methods such as asymmetrical and symmetrical phasing filter
      techniques. These resultant directional signals can be employed in order to
      detect asymptomatic embolic signals caused by small emboli, which are indicators
      of a possible future stroke, in the cerebral circulation. Various transform-based
      methods such as Fourier and wavelet were frequently used in processing embolic
      signals. However, most of the times, the Fourier and discrete wavelet transforms
      are not appropriate for the analysis of embolic signals due to their non
      stationary time-frequency behavior. Alternatively, discrete wavelet packet
      transform can perform an adaptive decomposition of the time-frequency axis. In
      this study, directional discrete wavelet packet transforms, which have the
      ability to map directional information while processing quadrature signals and
      have less computational complexity than the existing wavelet packet-based
      methods, are introduced. The performances of proposed methods are examined in
      detail by using single-frequency, synthetic narrow-band, and embolic quadrature
      signals. 

PMID- 25388780
TI  - Diabetes and work: 12-year national follow-up study of the association of
      diabetes incidence with socioeconomic group, age, gender and country of origin.
AB  - AIMS: To investigate the extent and socioeconomic distribution of incident
      diabetes among the Danish working-age population. METHODS: The Danish National
      Diabetes Register was linked with socioeconomic and population-based registers
      covering the entire population. We analysed the 12-year diabetes incidence using
      multivariate Poisson regression for 2,086,682 people, adjusting for gender, 10
      year age groups, main population groups defined by country of origin, and seven
      socioeconomic groups: professionals, managers, technicians, workers skilled at
      basic level, unskilled workers, unemployed and pensioners. RESULTS: The crude 12
      year incidence of diabetes was 5.8%. The saturated multivariate model, adjusted
      for gender, age, country of origin and socioeconomic status; showed a relative
      risk (RR) for diabetes incidence of 1.44 for male (reference: female), 3.95 for
      the age range of 50-59 years (reference: 30-39 years), 2.07 for unskilled workers
      (reference: professionals) and 2.15 for people from countries of 'non-Western
      origin' (reference: Danish origin). CONCLUSIONS: Diabetes incidence increases
      with age, male gender and low socioeconomic status; and also among people from
      countries of 'non-Western origin'. The results indicate that getting a more
      senior workforce will substantially increase the proportion of workers with
      diabetes, especially among already vulnerable groups.

PMID- 25388781
TI  - Inequalities in health care use among older adults in Sweden 1992-2011: a
      repeated cross-sectional study of Swedes aged 77 years and older.
AB  - AIMS: In the last decades, the Swedish health care system was reformed to promote
      free choice; however, it has been questioned whether older adults benefit from
      these reforms. It has also been proposed that reforms promoting free choice might
      increase inequalities in health care use. Thus, the aim of this study is to
      investigate socioeconomic differences in health care use among older adults in
      Sweden, from 1992 to 2011. METHODS: The Swedish Panel Study of the Living
      Conditions of the Oldest Old (SWEOLD) is a nationally representative study of
      Swedes over 76 years old, including both institutionalized and community-dwelling
      persons. We analyzed cross-sectional data from SWEOLD waves in 1992, 2002 and
      2011 (n ~ 600/wave); and performed multivariate analyses to investigate whether
      socioeconomic position was associated with health care use (inpatient, outpatient
      and dental services) after need was accounted for. RESULTS: For the period of
      1992-2011, we found that higher education was associated with more use of
      outpatient and dental care, both before and after adjustment for need. The
      association between education and inpatient or outpatient care use did not change
      over time. There was an increase in the proportion of older adults whom used
      dental care over the 19-year period, and there was a tendency for the
      socioeconomic differences regarding dentist visits to decrease over time.
      CONCLUSIONS: Our study covering 19 years showed relatively stable findings for
      socioeconomic differences in health care use among older adults in Sweden. We
      found there was a slight decrease in inequality in dental care; but unchanged
      socioeconomic differences in outpatient care, regardless of the changes that
      occurred in the Swedish health care system.

PMID- 25388782
TI  - Blood-brain barrier models: in vitro to in vivo translation in preclinical
      development of CNS-targeting biotherapeutics.
AB  - INTRODUCTION: The majority of therapeutics, small molecule or biologics,
      developed for the CNS do not penetrate the blood-brain barrier (BBB) sufficiently
      to induce pharmacologically meaningful effects on CNS targets. To improve the
      efficiency of CNS drug discovery, several in vitro models of the BBB have been
      used to aid early selection of molecules with CNS exposure potential. However,
      correlative studies suggest relatively poor predictability of in vitro BBB models
      underscoring the need to combine in vitro and in vivo BBB penetration assessment
      into an integrated preclinical workflow. AREAS COVERED: This review gives a brief
      general overview of in vitro and in vivo BBB models used in the pre-clinical
      evaluation of CNS-targeting drugs, with particular focus on the recent progress
      in developing humanized models. The authors discuss the advantages, limitations,
      in vitro-in vivo correlation, and integration of these models into CNS drug
      discovery and development with the aim of improving translation. EXPERT OPINION:
      Often, a simplistic rationalization of the CNS drug discovery and development
      process overlooks or even ignores the need for an early and predictive assessment
      of the BBB permeability. Indeed, past failures of CNS candidates in clinical
      trials argue strongly that the early deployment of in vitro and in vivo models
      for assessing BBB permeability, mechanisms of transport and brain exposure of
      leads, and the co-development of BBB delivery strategies will improve translation
      and increase the clinical success of CNS pipelines.

PMID- 25388783
TI  - Pulmonary arterial capacitance in patients with heart failure and reactive
      pulmonary hypertension.
AB  - AIMS: Reactive pulmonary hypertension (PH) is a severe form of PH secondary to
      left-sided heart failure (HF). Given the structural and functional abnormalities
      in the pulmonary vasculature that occur in reactive PH, we hypothesized that
      pulmonary artery capacitance (PAC) may be profoundly affected, with implications
      for clinical outcome. METHODS AND RESULTS: We studied 393 HF patients of whom 124
      (32%) were classified as having passive PH and 140 (36%) as having reactive PH,
      and 91 patients with pulmonary arterial hypertension (PAH). Mean PAC was highest
      in patients without PH (4.5 +/- 2.1 mL/mmHg), followed by the passive PH group
      (2.8 +/- 1.4 mL/mmHg) and was lowest in those with reactive PH (1.8 +/- 0.7
      mL/mmHg) (P = 0.0001). PAC and pulmonary vascular resistance (PVR) fitted well to
      a hyperbolic inverse relationship (PAC = 0.25/PVR, R(2)  = 0.70), with reactive
      PH patients dispersed almost predominantly on the flat part of the curve where a
      reduction in PVR is associated with a small improvement in PAC. Elevated PCWP was
      associated with a significant lowering of PAC for any PVR (P = 0.036). During a
      median follow-up of 31 months, both reactive PH [hazard ratio (HR) 2.59, 95%
      confidence interval (CI) 1.14-4.46, P = 0.02] and reduced PAC (HR 0.72 per 1
      mL/mmHg increase, 95% CI 0.59-0.88, P = 0.001) were independent predictors of
      mortality. CONCLUSIONS: The development of reactive PH is associated with a
      marked reduction in PAC. PAC is a strong independent haemodynamic marker of
      mortality in HF and may contribute to the increased mortality associated with
      reactive PH.

PMID- 25388784
TI  - Hypermethylation of repeat expanded C9orf72 is a clinical and molecular disease
      modifier.
AB  - C9orf72 promoter hypermethylation inhibits the accumulation of pathologies which
      have been postulated to be neurotoxic. We tested here whether C9orf72
      hypermethylation is associated with prolonged disease in C9orf72 mutation
      carriers. C9orf72 methylation was quantified from brain or blood using
      methylation-sensitive restriction enzyme digest-qPCR in a cross-sectional cohort
      of 118 C9orf72 repeat expansion carriers and 19 non-carrier family members.
      Multivariate regression models were used to determine whether C9orf72
      hypermethylation was associated with age at onset, disease duration, age at
      death, or hexanucleotide repeat expansion size. Permutation analysis was
      performed to determine whether C9orf72 methylation is heritable. We observed a
      high correlation between C9orf72 methylation across tissues including cerebellum,
      frontal cortex, spinal cord and peripheral blood. While C9orf72 methylation was
      not significantly different between ALS and FTD and did not predict age at onset,
      brain and blood C9orf72 hypermethylation was associated with later age at death
      in FTD (brain: beta = 0.18, p = 0.006; blood: beta = 0.15, p < 0.001), and blood
      C9orf72 hypermethylation was associated with longer disease duration in FTD (beta
      = 0.03, p = 0.007). Furthermore, C9orf72 hypermethylation was associated with
      smaller hexanucleotide repeat length (beta = -16.69, p = 0.033). Finally,
      analysis of pedigrees with multiple mutation carriers demonstrated a significant
      association between C9orf72 methylation and family relatedness (p < 0.0001).
      C9orf72 hypermethylation is associated with prolonged disease in C9orf72 repeat
      expansion carriers with FTD. The attenuated clinical phenotype associated with
      C9orf72 hypermethylation suggests that slower clinical progression in FTD is
      associated with reduced expression of mutant C9orf72. These results support the
      hypothesis that expression of the hexanucleotide repeat expansion is associated
      with a toxic gain of function.

PMID- 25388785
TI  - Pathogenic Ubqln2 gains toxic properties to induce neuron death.
AB  - Mutations in ubiquilin 2 (Ubqln2) is linked to amyotrophic lateral sclerosis and
      frontotemporal lobar degeneration. A foremost question regarding Ubqln2
      pathogenesis is whether pathogenically mutated Ubqln2 causes neuron death via a
      gain or loss of functions. To better understand Ubqln2 pathobiology, we created
      Ubqln2 transgenic and knockout rats and compared phenotypic expression in these
      novel rat models. Overexpression of Ubqln2 with a pathogenic mutation (P497H
      substitution) caused cognitive deficits and neuronal loss in transgenic rats at
      the age of 130 days. In the transgenic rats, neuronal loss was preceded by the
      progressive formation of Ubqln2 aggregates and was accompanied by the progressive
      accumulation of the autophagy substrates p62 and LC3-II and the impairment of
      endosome pathways. In contrast, none of these pathologies observed in mutant
      Ubqln2 transgenic rats was detected in Ubqln2 knockout rats at the age of 300
      days. Together, our findings in Ubqln2 transgenic and knockout rats collectively
      suggest that pathogenic Ubqln2 causes neuron death mainly through a gain of
      unrevealed functions rather than a loss of physiological functions. 

PMID- 25388786
TI  - Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3
      deficiency in a family with hereditary spherocytosis.
AB  - In a family with mild dominant spherocytosis, affected members showed partial
      band 3 deficiency. The index patient showed more severe clinical symptoms than
      his relatives, and his red blood cells displayed concomitant low pyruvate kinase
      activity. We investigated the contribution of partial PK deficiency to the
      phenotypic expression of mutant band 3 in this family. Pyruvate kinase deficiency
      and band 3 deficiency were characterized by DNA analysis. Results of red cell
      osmotic fragility testing, the results of cell deformability obtained by the
      Automated Rheoscope and Cell Analyzer and the results obtained by Osmotic
      Gradient Ektacytometry, which is a combination of these tests, were related to
      the red cell ATP content. Spherocytosis in this family was due to a novel
      heterozygous mutation in SLC4A1, the gene for band 3. Reduced PK activity of the
      index patient was attributed to a novel mutation in PKLR inherited from his
      mother, who was without clinical symptoms. Partial PK deficiency was associated
      with decreased red cell ATP content and markedly increased osmotic fragility.
      This suggests an aggravating effect of low ATP levels on the phenotypic
      expression of band 3 deficiency.

PMID- 25388787
TI  - Searching for Dual Inhibitors of the MDM2-p53 and MDMX-p53 Protein-Protein
      Interaction by a Scaffold-Hopping Approach.
AB  - Two libraries of substituted benzimidazoles were designed using a 'scaffold
      hopping' approach based on reported MDM2-p53 inhibitors. Substituents were chosen
      following library enumeration and docking into an MDM2 X-ray structure.
      Benzimidazole libraries were prepared using an efficient solution-phase approach
      and screened for inhibition of the MDM2-p53 and MDMX-p53 protein-protein
      interactions. Key examples showed inhibitory activity against both targets. 

PMID- 25388788
TI  - Ion-activated attractive patches as a mechanism for controlled protein
      interactions.
AB  - The understanding of protein interactions to control phase and nucleation
      behavior of protein solutions is an important challenge for soft matter,
      biological and medical research. Here, we present ion bridges of multivalent
      cations between proteins as an ion-activated mechanism for patchy interaction
      that is directly supported by experimental findings in protein crystals. A deep
      understanding of experimentally observed phenomena in protein solutions-
      including charge reversal, reentrant condensation, metastable liquid-liquid phase
      separation, cluster formation and different pathways of crystallization--is
      gained by an analytic model that directly displays parameter dependencies and
      physical connections. The direct connection between experiment and theory
      provides a conceptual framework for future experimental, computational and
      theoretical research on topics such as rational design of phase behavior and
      crystallization pathways on the basis of the statistical physics of patchy
      particles.

PMID- 25388789
TI  - Targeted genomic capture and massively parallel sequencing to identify novel
      variants causing Chinese hereditary hearing loss.
AB  - BACKGROUND: Hereditary hearing loss is genetically heterogeneous, and hundreds of
      mutations in than 60 genes are involved in this disease. Therefore, it is
      difficult to identify the causative gene mutations involved. In this study, we
      combined targeted genomic capture and massively parallel sequencing (MPS) to
      address this issue. METHODS: Using targeted genomic capture and MPS, 104 genes
      and three microRNA regions were selected and simultaneously sequenced in 23
      unrelated probands of Chinese families with nonsyndromic hearing loss. The
      results were validated by Sanger sequencing for all available members of the
      probands' families. To analyze the possible pathogenic functional effects of the
      variants, three types of prediction programs (Mutation Taster, PROVEAN and SIFT)
      were used. A total of 195 healthy Chinese Han individuals were compared as
      controls to verify the novel causative mutations. RESULTS: Of the 23 probands,
      six had mutations in DFNA genes [WFS1 (n = 2), COCH, ACTG1, TMC1, and POU4F3]
      known to cause autosomal dominant nonsyndromic hearing loss. These included one
      novel in-frame indel mutation, three novel missense mutations and two reported
      missense mutations. Furthermore, one proband from a family with recessive DFNB
      carried two monoallelic mutations in the GJB2 and USH2A genes. All of these
      mutations co-segregated with the hearing loss phenotype in 36 affected
      individuals from 7 families and were predicted to be pathogenic. CONCLUSIONS:
      Mutations in uncommon deafness genes contribute to a portion of nonsyndromic
      deafness cases. In the future, critical gene mutations may be accurately and
      quickly identified in families with hereditary hearing loss by targeted genomic
      capture and MPS.

PMID- 25388790
TI  - Heterotopic gastric mucosa associated with abdominal abscess formation,
      hypotension, and acute abdominal pain in a puppy.
AB  - OBJECTIVE: To describe the presence of heterotopic gastric mucosa forming an
      abscess associated with acute abdominal pain and shock in a puppy. CASE SUMMARY:
      A 7-month-old male intact Shih-Tzu was presented to the emergency service for
      evaluation of a 12-hour history of vomiting and lethargy progressing to weakness.
      On presentation, the puppy was obtunded and hypotensive. Radiographs revealed an
      ill-defined mid-ventral abdominal mass. Ultrasound revealed an echogenic, fluid
      filled mass associated with the jejunum. The puppy had an exploratory celiotomy
      and a 2 * 4 cm oval fluid-filled soft tissue mass was found to be intimately
      associated, but not communicating with, a section of the mid-jejunum. The mass
      and associated jejunum were removed via enterectomy. Histopathology of the
      resected mass revealed heterotopic gastric mucosa; bacterial culture of the fluid
      contained in the mass revealed heavy growth of Escherichia coli. The puppy
      recovered from surgery, was discharged from the hospital, and has had no further
      complications from this episode. UNIQUE INFORMATION PROVIDED: Heterotopic gastric
      mucosa is commonly found incidentally on necropsy. When it has been associated
      with acute gastrointestinal signs, mechanical intestinal obstruction with or
      without perforation was noted. To the authors' knowledge, this is the first
      reported case of heterotopic gastric mucosa leading to abscess formation and
      acute abdominal pain in the dog.

PMID- 25388791
TI  - Transoral robotic surgery in benign diseases including obstructive sleep apnea:
      Safety and feasibility.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the safety and feasibility of the da Vinci
      Surgical System in transoral robotic-assisted surgery for benign indications.
      STUDY DESIGN: A multicenter, single-arm, retrospective case series. METHODS:
      Perioperative outcomes were recorded for patients presenting with obstructive
      sleep apnea, airway obstruction, lingual tonsillar/tonsillar/tongue base
      hypertrophy, or dysphagia who underwent one or more transoral procedures,
      including lingual tonsillectomy and tongue base resection (partial glossectomy)
      at one of three US institutions. RESULTS: Between January 2010 and October 2013,
      285 patients (age 51.5 years, body mass index 30.5 kg/m(2) ) underwent 293
      procedures. No conversions or blood transfusions were needed. The average
      operative time was 86.7 minutes, and the average volume of tissue resected
      (lingual tonsil and tongue base) was 8.3 mL. Hospital stays averaged 1.8 days,
      and the postoperative complication rate was 20.7%. There were no complications
      specifically related to the use the da Vinci Surgical System, and none of the
      complications were life threatening. CONCLUSIONS: These results demonstrate that
      it is safe and feasible to use the da Vinci Surgical System to perform lingual
      tonsillectomy and base of tongue resection (partial glossectomy) procedures for
      benign indications. LEVEL OF EVIDENCE: 4

PMID- 25388792
TI  - Non-vertebral Veillonella species septicemia and osteomyelitis in a patient with
      diabetes: a case report and review of the literature.
AB  - INTRODUCTION: Veillonella is a nonfermentative, strictly anaerobic, Gram-negative
      coccus that forms part of the human gastrointestinal tract, mouth and vaginal
      flora. Like other anaerobic infection, Veillonella species usually are involved
      in polymicrobial processes, which make it difficult to determine their pathogenic
      role. Isolation of a clinically significant Veillonella species is rare and V.
      parvula is the most common one reported to cause infection in humans. The most
      frequently reported infection caused by V. parvula is osteomyelitis, almost
      always in association with bacteremia. CASE PRESENTATION: Here, we describe a
      rare case of nonvertebral osteomyelitis and septicemia caused by Veillonella
      species in a 49-year-old Saudi man with diabetes. Initial treatment with
      ciprofloxacin was associated with treatment failure and poor response.
      Identification of the organism was essential for the selection of appropriate
      treatment. There have been only seven previous reports of Veillonella vertebral
      osteomyelitis and one report of V. parvula foot osteomyelitis with sepsis in the
      literature. This is the second case of Veillonella nonvertebral osteomyelitis
      associated with septicemia reported to date. CONCLUSIONS: Veillonella species
      should be considered a true pathogen in diabetic patients with osteomyelitis and
      those with underlying immune suppression, particularly if the organism is
      isolated from blood. The isolation of those obligate anaerobes from blood may
      signal the presence of severe underlying disease and the probable need for timely
      surgical intervention.

PMID- 25388793
TI  - Experimental verification of SNR and parallel imaging improvements using
      composite arrays.
AB  - Composite MRI arrays consist of triplets where two orthogonal upright loops are
      placed over the same imaging area as a standard surface coil. The optimal height
      of the upright coils is approximately half the width for the 7 cm coils used in
      this work. Resistive and magnetic coupling is shown to be negligible within each
      coil triplet. Experimental evaluation of imaging performance was carried out on a
      Philips 3 T Achieva scanner using an eight-coil composite array consisting of
      three surface coils and five upright loops, as well as an array of eight surface
      coils for comparison. The composite array offers lower overall coupling than the
      traditional array. The sensitivities of upright coils are complementary to those
      of the surface coils and therefore provide SNR gains in regions where surface
      coil sensitivity is low, and additional spatial information for improved parallel
      imaging performance. Near the surface of the phantom the eight-channel surface
      coil array provides higher overall SNR than the composite array, but this
      advantage disappears beyond a depth of approximately one coil diameter, where it
      is typically more challenging to improve SNR. Furthermore, parallel imaging
      performance is better with the composite array compared with the surface coil
      array, especially at high accelerations and in locations deep in the phantom.
      Composite arrays offer an attractive means of improving imaging performance and
      channel density without reducing the size, and therefore the loading regime, of
      surface coil elements. Additional advantages of composite arrays include minimal
      SNR loss using root-sum-of-squares combination compared with optimal, and the
      ability to switch from high to low channel density by merely selecting only the
      surface elements, unlike surface coil arrays, which require additional hardware.

PMID- 25388794
TI  - Unusual presentation of advanced prostate cancer masquerading as metastatic and
      obstructing rectosigmoid cancer.

PMID- 25388795
TI  - Ultrasound of cervical roots and brachial plexus in neonates.

PMID- 25388796
TI  - Abnormal incorporation of amino acids into the gas hydrate crystal lattice.
AB  - Gas hydrates are crystalline ice-like solid materials enclosing gas molecules
      inside. The possibility of the presence of gas hydrates with amino acids in the
      universe is of interest when revealing the potential existence of life as they
      are evidence of a source of water and organic precursors, respectively. However,
      little is known about how they can naturally coexist, and their crystallization
      behavior would become far more complex as both crystallize with formation of
      hydrogen bonds. Here, we report abnormal incorporation of amino acids into the
      gas hydrate crystal lattice that is contrary to the generally accepted
      crystallization mode, and this resulted in lattice distortion and expansion. The
      present findings imply the potential for their natural coexistence by sharing the
      crystal lattice, and will be helpful for understanding the role of additives in
      the gas hydrate crystallization. 

PMID- 25388797
TI  - A rare case of narrow QRS complex tachycardia.

PMID- 25388798
TI  - First Dutch experience with the endoscopic laser balloon ablation system for the
      treatment of atrial fibrillation.
AB  - INTRODUCTION: The endoscopic laser balloon ablation system (EAS) is a relatively
      novel technique to perform pulmonary vein isolation (PVI) in the treatment of
      atrial fibrillation (AF). The present study aimed to report the results of the
      first 50 patients treated in the Netherlands with the EAS in terms of procedural
      characteristics and AF-free survival. METHODS: Fifty patients successfully
      underwent EAS PVI. Median follow-up was 17 months. Mean age was 56 years, 82 %
      had paroxysmal AF. RESULTS: 99 % of the pulmonary veins were successfully
      isolated with the EAS. Mean procedure time was 171 min and mean fluoroscopy time
      was 36 min. One procedure was complicated by a temporary phrenic nerve palsy (2
      %). During follow-up, 58 % of patients remained free of AF without the use of
      antiarrhythmic drugs. CONCLUSION: PVI with EAS is associated with a low risk of
      complications and a medium-term AF-free survival comparable with other PVI
      techniques.

PMID- 25388800
TI  - International testicular cancer incidence trends: generational transitions in 38
      countries 1900-1990.
AB  - PURPOSE: Rapid increases in testicular cancer incidence have marked the second
      half of the last century. While these secular rises, observed mainly in countries
      attaining the highest levels of human development, appear to have attenuated in
      the last decade, rates continue to increase in countries transiting toward high
      developmental levels. The purpose of our study was to provide a comprehensive
      analysis and presentation of the cohort-specific trends in testicular cancer
      incidence rates in 38 countries worldwide. METHODS: We used an augmented version
      of the Cancer Incidence in Five Continents series to analyze testicular cancer
      incidence in men aged 15-54 in 38 countries, via age-period-cohort analysis.
      RESULTS: In many European countries, the USA, Canada, Australia, and New Zealand,
      there is a continuation of the increasing risk among successive generations, yet
      rates are attenuating in male cohorts born since the 1970s in several Northern
      European countries, in contrast to the steeply increasing trends in recent
      cohorts in Southern Europe. Incidence rates have also been increasing in the
      populations traditionally at rather low risk, such as in the Philippines,
      Singapore, China, and Costa Rica. CONCLUSIONS: The attenuation of testicular
      cancer risk in younger generations (in the most developed countries) alongside
      concomitant increases (in countries undergoing developmental change) is
      indicative of a global transition in the risk of testicular cancer. While
      identifying the underlying causes remains a major challenge, increasing awareness
      and adapting national healthcare systems to accommodate a growing burden of
      testicular cancer may prevent future avoidable deaths in young men.

PMID- 25388799
TI  - Circadian clock genes and risk of fatal prostate cancer.
AB  - PURPOSE: Circadian genes may be involved in regulating cancer-related pathways,
      including cell proliferation, DNA damage response, and apoptosis. We aimed to
      assess the role of genetic variation in core circadian rhythm genes with the risk
      of fatal prostate cancer and first morning void urinary 6-sulfatoxymelatonin
      levels. METHODS: We used unconditional logistic regression to evaluate the
      association of 96 single-nucleotide polymorphisms (SNPs) across 12 circadian
      related genes with fatal prostate cancer in the AGES-Reykjavik cohort (n = 24
      cases), the Health Professionals Follow-Up Study (HPFS) (n = 40 cases), and the
      Physicians' Health Study (PHS) (n = 105 cases). We used linear regression to
      evaluate the association between SNPs and first morning void urinary 6
      sulfatoxymelatonin levels in AGES-Reykjavik. We used a kernel machine test to
      evaluate whether multimarker SNP sets in the pathway (gene based) were associated
      with our outcomes. RESULTS: None of the individual SNPs were consistently
      associated with fatal prostate cancer across the three cohorts. In each cohort,
      gene-based analyses showed that variation in the CRY1 gene was nominally
      associated with fatal prostate cancer (p values = 0.01, 0.01, and 0.05 for AGES
      Reykjavik, HPFS, and PHS, respectively). In AGES-Reykjavik, SNPs in TIMELESS
      (four SNPs), NPAS2 (six SNPs), PER3 (two SNPs) and CSNK1E (one SNP) were
      nominally associated with 6-sulfatoxymelatonin levels. CONCLUSION: We did not
      find a strong and consistent association between variation in core circadian
      clock genes and fatal prostate cancer risk, but observed nominally significant
      gene-based associations with fatal prostate cancer and 6-sulfatoxymelatonin
      levels.

PMID- 25388802
TI  - Formation of gapless triplets in the bond-doped spin-gap antiferromagnet
      (C4H12N2)(Cu2Cl6).
AB  - We report results of an electron spin resonance (ESR) study of a spin-gap
      antiferromagnet (C(4)H(12)N(2))(Cu(2(Cl(6)) (nicknamed PHCC) with chlorine ions
      partially substituted by bromine. We found that up to 10% of nominal doping the
      contribution of the random defects to the absorption spectra remains at about
      0.1% per copper ion, which is almost the same as in the pure system. Instead, a
      particular kind of ESR absorption corresponding to gapless S = 1 triplets is
      observed at low temperatures in samples with high nominal bromine content x >=
      5%. Increase of bromine concentration also leads to the systematic broadening of
      ESR absorption line, indicating reduction of the quasi-particles lifetime.

PMID- 25388801
TI  - Objective allergy markers and risk of cancer mortality and hospitalization in a
      large population-based cohort.
AB  - PURPOSE: There are indications that a history of allergy may offer some
      protection against cancer. We studied the relation of three objectively
      determined allergy markers with cancer mortality and hospitalization risk.
      METHODS: Associations between three allergy markers (number of peripheral blood
      eosinophil counts, skin test positivity, and serum total IgE) with mortality and
      hospitalization from any type and four common types of cancer (lung, colorectal,
      prostate, and breast cancer) were assessed in the Vlagtwedde-Vlaardingen cohort
      (1965-1990), with follow-up of mortality until 31 December 2008. Hospitalization
      data were available since 1 January 1995. RESULTS: There were no significant
      associations between objective allergy markers and cancer mortality or
      hospitalization. We found several associations in specific subgroups. A higher
      number of eosinophils was associated with a decreased risk of colorectal cancer
      mortality in ever smokers HR (95 % CI) = 0.61 (0.45-0.83) and in males 0.59 (0.42
      0.83); however, no overall association was observed 0.84 (0.64-1.09). Skin test
      positivity was associated with a decreased risk of any cancer mortality only
      among females 0.59 (0.38-0.91) and showed no overall association 0.83 (0.67
      1.04). Serum total IgE levels were associated with an increased risk of lung
      cancer mortality among females 4.64 (1.04-20.70), but with a decreased risk of
      cancer hospitalization in ever smokers 0.77 (0.61-0.97) and males 0.72 (0.55
      0.93); however, no overall associations were observed [mortality 0.99 (0.79
      1.25), and hospitalization 0.86 (0.71-1.04)]. CONCLUSIONS: We found no
      associations between objective allergy markers and cancer in the total
      population. However, skin test positivity and a high number of eosinophils were
      associated with a reduced risk to die of cancer in specific subgroups. Hence, it
      seems important to study specific subgroups defined by gender and smoking habits
      in order to identify allergy markers of predictive value for cancer mortality.

PMID- 25388803
TI  - New clustering methods for population comparison on paternal lineages.
AB  - The goal of this study is to show two new clustering and visualising techniques
      developed to find the most typical clusters of 18-dimensional Y chromosomal
      haplogroup frequency distributions of 90 Western Eurasian populations. The first
      technique called "self-organizing cloud (SOC)" is a vector-based self-learning
      method derived from the Self Organising Map and non-metric Multidimensional
      Scaling algorithms. The second technique is a new probabilistic method called the
      "maximal relation probability" (MRP) algorithm, based on a probability function
      having its local maximal values just in the condensation centres of the input
      data. This function is calculated immediately from the distance matrix of the
      data and can be interpreted as the probability that a given element of the
      database has a real genetic relation with at least one of the remaining elements.
      We tested these two new methods by comparing their results to both each other and
      the k-medoids algorithm. By means of these new algorithms, we determined 10
      clusters of populations based on the similarity of haplogroup composition. The
      results obtained represented a genetically, geographically and historically well
      interpretable picture of 10 genetic clusters of populations mirroring the early
      spread of populations from the Fertile Crescent to the Caucasus, Central Asia,
      Arabia and Southeast Europe. The results show that a parallel clustering of
      populations using SOC and MRP methods can be an efficient tool for studying the
      demographic history of populations sharing common genetic footprints. 

PMID- 25388804
TI  - A clozapine conundrum: clozapine toxicity in an acute medical illness.
AB  - OBJECTIVE: The following report presents a case in which significant clozapine
      toxicity was demonstrated in a patient on established therapy, in the absence of
      identifiable risk factors. Through this case report, the authors aim to highlight
      the potential for clozapine toxicity to occur unexpectedly in times of acute
      medical illness, and the need to remain vigilant in such situations. METHODS:
      Case report and review of the relevant literature. RESULTS: We describe a case of
      a 62 year old man whom developed life-threatening clozapine toxicity in the
      context of a severe lower respiratory infection. Following investigation to
      exclude the usual causes of toxicity, it was surmised that impaired CYP1A2
      function, secondary to the acute inflammatory process, had led to a toxic level
      of the drug. CONCLUSIONS: Given the possibility that serum clozapine levels may
      significantly rise in acute illness, the team recommends measurement of clozapine
      levels in these situations, in combination with the usual full blood count
      investigation. Such a practice should be considered in the local monitoring
      protocol, to avoid incidence of potentially toxic outcomes.

PMID- 25388805
TI  - Transcutaneous measurement of glomerular filtration rate in small rodents:
      through the skin for the win?
AB  - Rodent models of renal physiology and pathology are crucial to our understanding
      of the molecular, histological and functional sequelae that contribute to kidney
      diseases. One of the most important measures of renal function is glomerular
      filtration rate (GFR). While the accurate determination of GFR is pivotal to
      understanding the progression of disease and/or the benefits of treatment
      strategies, in rodents the conventional methods for assessment of GFR are
      inconvenient and cumbersome, not the least because they involve stress and often
      anaesthesia. The legitimacy of assay-based assessment of plasma and urine markers
      of GFR in mice has also been heavily scrutinized for their insensitivity to minor
      declines in GFR and inaccurate detection of renal biomarkers. While infusion
      based clearance methods of GFR assessment are thus the gold standard in terms of
      accuracy, they are limited by the fact that they are primarily non-recovery
      procedures. This presents a dilemma when trying to document the progression of
      renal disease, as these measures cannot be taken in the same experimental
      subject. Here we review a technique of transcutaneous measurement of fluorescein
      isothiocyanate-labelled sinistrin to calculate GFR in small rodents, using a non
      invasive clearance device (NIC-Kidney Device). This is a recently validated non
      invasive technique for measuring GFR in small rodents that allows for the real
      time measurement of GFR in conscious animals, without the need for plasma and
      urine assays. 

PMID- 25388806
TI  - Late-onset volvulus without malrotation in extremely preterm infants--a case
      control-study.
AB  - BACKGROUND: Volvulus without malrotation in preterm infants is a rare but
      potentially life-threatening event of unknown aetiology. Confusion with
      necrotising enterocolitis may delay surgical intervention thereby aggravating
      morbidity and mortality. We aimed at elucidating potential risk factors for, and
      characteristic clinical signs of, volvulus without malrotation in preterm
      infants. METHODS: Retrospective, single-centre case-control study (2007-2011).
      For every index patient, five infants of similar gestational age, birth weight
      and birth year were evaluated. Additionally, all 9 cases of necrotising
      enterocolitis occurring during the above period were evaluated. Data are
      presented as median (interquartile range). RESULTS: Five extremely premature
      infants suffering from volvulus without malrotation were identified (gestational
      age at birth 24.4 (23.6-25.5) weeks, birth weight 480 (370-530) g). All were
      small for gestational age and female; three out of five died. Volvulus occurred
      several weeks after birth, whereas necrotising enterocolitis occurred
      significantly earlier. Beyond that, no striking differences in clinical or
      laboratory presentation of volvulus without malrotation and necrotising
      enterocolitis were found. Infants with volvulus had significantly more frequent
      manipulations with rectal tubes for flatulence, but there were no differences in
      the frequency of enemas, abdominal massage or defecation. In infants with
      volvulus, nasal high-frequency oscillation was used more frequently for
      respiratory support, and PEEP-level tended to be higher. CONCLUSIONS: In
      extremely premature infants volvulus without malrotation represents a life
      threatening event that occurs typically several weeks after birth with an acute
      abdomen and seems to affect predominantly girls. Infants requiring intensive non
      invasive respiratory support might be at highest risk.

PMID- 25388807
TI  - Investigating the molecular underpinnings underlying morphology and changes in
      carbon partitioning during tension wood formation in Eucalyptus.
AB  - Tension wood has distinct physical and chemical properties, including altered
      fibre properties, cell wall composition and ultrastructure. It serves as a good
      system for investigating the genetic regulation of secondary cell wall
      biosynthesis and wood formation. The reference genome sequence for Eucalyptus
      grandis allows investigation of the global transcriptional reprogramming that
      accompanies tension wood formation in this global wood fibre crop. We report the
      first comprehensive analysis of physicochemical wood property changes in tension
      wood of Eucalyptus measured in a hybrid (E. grandis * Eucalyptus urophylla)
      clone, as well as genome-wide gene expression changes in xylem tissues 3 wk post
      induction using RNA sequencing. We found that Eucalyptus tension wood in field
      grown trees is characterized by an increase in cellulose, a reduction in lignin,
      xylose and mannose, and a marked increase in galactose. Gene expression profiling
      in tension wood-forming tissue showed corresponding down-regulation of monolignol
      biosynthetic genes, and differential expression of several carbohydrate active
      enzymes. We conclude that alterations of cell wall traits induced by tension wood
      formation in Eucalyptus are a consequence of a combination of down-regulation of
      lignin biosynthesis and hemicellulose remodelling, rather than the often proposed
      up-regulation of the cellulose biosynthetic pathway.

PMID- 25388809
TI  - Dental fast track: prenatal enamel growth, incisor eruption, and weaning in human
      infants.
AB  - Correlation between the timing of permanent first molar eruption and weaning age
      in extant primates has provided a way to infer a life history event in fossil
      species, but recent debate has questioned whether the same link is present in
      human infants. Deciduous incisors erupt at an age when breast milk can be
      supplemented with additional foods (mixed feeding), and weaning is typically
      complete before permanent first molars erupt. Here, I use histological methods to
      calculate the prenatal rate by which enamel increases in thickness and height on
      human deciduous incisors, canines, and molars (n = 125). Growth trajectories for
      each tooth type are related to the trimesters and assessed against the eruption
      sequence and final crown height. Analyses show that central incisors initiate
      early in the second trimester with significantly faster secretion rates relative
      to canines and second molars, which initiate closer to birth. Even though initial
      extension rates were correlated with crown height and scaled with positive
      allometry within each tooth class, the relatively short incisors still increased
      in height at a significantly faster rate than the taller canines and molars. The
      incisor prenatal "fast track" produces a greater proportion of the crown before
      birth than all other tooth types. This growth mechanism likely facilitates early
      incisor eruption at a time when the mixed feeding of infants can be initiated as
      part of the weaning process. Findings provide a basis from which to explore new
      links between developmental trends along the tooth row and mixed feeding age in
      other primates.

PMID- 25388808
TI  - Quality of life and metrics of achievement in long-term adult survivors of
      pediatric heart transplant.
AB  - Many children who undergo heart transplantation will survive into adulthood. We
      sought to examine the QOL and capacity for achievement in long-term adult
      survivors of pediatric heart transplantation. Adults >18 yr of age who received
      transplants as children (<=18 yr old) and had survived for at least 10 yr post
      transplant completed two self-report questionnaires: (i) Ferrans & Powers QLI, in
      which life satisfaction is reported as an overall score and in four subscale
      domains and is then indexed from 0 (very dissatisfied) to 1 (very satisfied); and
      (ii) a "Metrics of Life Achievement" questionnaire regarding income, education,
      relationships, housing status, and access to health care. A total of 20 subjects
      completed the survey. The overall mean QLI score was 0.77 +/- 0.16. Subjects were
      most satisfied in the family domain (0.84 +/- 0.21) and least satisfied in the
      psychological/spiritual domain (0.7 +/- 0.28). Satisfaction in the domains of
      health/functioning and socioeconomic were intermediate at 0.78 and 0.76,
      respectively. Most respondents had graduated from high school, reported a median
      annual income >$50 000/yr, and lived independently. Adult survivors of pediatric
      heart transplant report a good QOL and demonstrate the ability to obtain an
      education, work, and live independently. 

PMID- 25388810
TI  - In vivo label-free quantification of liver microcirculation using dual-modality
      microscopy.
AB  - Microcirculation lesion is a common symptom of chronic liver diseases in the form
      of vasculature deformation and circulation alteration. In acute to chronic liver
      diseases such as biliary atresia, microcirculation lesion can have an early
      onset. Detection of microcirculation lesion is meaningful for studying the
      progression of liver disease. We have combined wide-field fluorescence microscopy
      and a laser speckle contrast technique to characterize hepatic microcirculation
      in vivo without labeling in a bile-duct ligation rat fibrosis model of biliary
      atresia. Through quantitative image analysis of four microcirculation parameters,
      we observed significant microcirculation lesion in the early to middle stages of
      fibrosis. This bimodal imaging method is useful to assess hepatic
      microcirculation lesion for the study of liver diseases.

PMID- 25388811
TI  - Optical fiber sensors-based temperature distribution measurement in ex vivo
      radiofrequency ablation with submillimeter resolution.
AB  - Radiofrequency thermal ablation (RFTA) induces a high-temperature field in a
      biological tissue having steep spatial (up to 6 degrees C/mm) and temporal (up to
      1 degrees C/s) gradients. Applied in cancer care, RFTA produces a localized
      heating, cytotoxic for tumor cells, and is able to treat tumors with sizes up to
      3 to 5 cm in diameter. The online measurement of temperature distribution at the
      RFTA point of care has been previously carried out with miniature thermocouples
      and optical fiber sensors, which exhibit problems of size, alteration of RFTA
      pattern, hysteresis, and sensor density worse than 1 sensor/cm. In this work, we
      apply a distributed temperature sensor (DTS) with a submillimeter spatial
      resolution for the monitoring of RFTA in porcine liver tissue. The DTS
      demodulates the chaotic Rayleigh backscattering pattern with an interferometric
      setup to obtain the real-time temperature distribution. A measurement chamber has
      been set up with the fiber crossing the tissue along different diameters. Several
      experiments have been carried out measuring the space-time evolution of
      temperature during RFTA. The present work showcases the temperature monitoring in
      RFTA with an unprecedented spatial resolution and is exportable to in vivo
      measurement; the acquired data can be particularly useful for the validation of
      RFTA computational models.

PMID- 25388813
TI  - Tunable photoluminescence and direct white-light emission in Mg-based
      coordination networks.
AB  - The bpy, dpe and dppe were introduced as auxiliary ligands, respectively, to
      construct three magnesium-1,4-NDC coordination polymers (Mg-CPs) that exhibited
      tunable photoluminescence (PL) and direct white-light emission upon varying the
      excitation light. 

PMID- 25388812
TI  - Cadmium exposure and age-related macular degeneration.
AB  - Cadmium (Cd) has been proposed as a risk factor for age-related macular
      degeneration (AMD), but the association between Cd exposure and AMD risk in large
      population studies is unknown. This study evaluated the association of Cd
      exposure with AMD in a large representative sample of Korean men and women. This
      was a cross-sectional study of 3865 Korean adults >= 40 years of age who
      participated in the Korean National Health and Nutrition Examination Survey
      (KNHANES) during 2008-2011. Cd concentrations in whole blood were measured by
      graphite-furnace atomic absorption spectrometry. The presence of AMD was
      determined in digital non-mydriatic fundus photographs. Cd levels were higher in
      participants with AMD compared with those without AMD (1.3 vs 1.1 MUg/l,
      respectively, P<0.001). In fully adjusted models, the odds ratio for AMD
      comparing the highest with the lowest Cd quartiles was 1.92 (95% CI=1.08-3.39; P
      for trend 0.029). In restricted cubic spline models, the association between Cd
      and AMD was approximately linear, with no evidence of threshold effects. Blood Cd
      concentrations were independently associated with the prevalence of AMD. If the
      association is proven causal, population-based preventive strategies to decrease
      Cd exposure could reduce the population burden of AMD.

PMID- 25388815
TI  - Which biotech foods are most acceptable to the public?
AB  - New discoveries are prompting questions about which types of genetically
      engineered foods and applications are likely to be most accepted by the public.
      Results of a survey of over 1000 US consumers reveals that people prefer eating
      beef to eating corn or apples if the foods are not genetically engineered, but
      exactly the opposite is true if the foods are genetically engineered. Eating
      fresh food is preferred to processed, but much less so if both food types are
      genetically engineered. Desirability of genetic engineering depends on the reason
      for the biotechnology application. 

PMID- 25388817
TI  - Notalgia paresthetica: treatment with topical tacrolimus.

PMID- 25388818
TI  - Palmoplantar keratosis in oculodentodigital dysplasia with a GJA1 point mutation
      out of the C-terminal region of connexin 43.
AB  - Gap junction proteins are composed of 21 genes of the connexin (Cx) family. They
      play important roles in cell-cell contact by exchange of small molecules through
      hemichannels. Hence, mutations of Cx family genes affect various tissues of a
      body. The mutation of the GJA1 gene, which codes Cx43, causes oculodentodigital
      dysplasia (ODDD), commonly in an autosomal dominant manner with phenotypic
      variability. It has been believed that gene mutations causing truncation of the
      Cx43 C-terminus is necessary and sufficient for palmoplantar keratosis (PPK)
      development in ODDD patients. Here, we report a case of an ODDD patient
      developing PPK with a GJA1 gene mutation (c.412G>A/p.Gly138Ser), which was
      previously reported in a case of ODDD without PPK and expected not to result in C
      terminal truncation of Cx43. This case suggests not only C-terminal truncation,
      but also that a point mutation in the cytoplasmic region of Cx43 can cause PPK in
      ODDD patients. 

PMID- 25388819
TI  - Effect of water temperature and population density on the population dynamics of
      Schistosoma mansoni intermediate host snails.
AB  - BACKGROUND: Mathematical models can be used to identify areas at risk of
      increased or new schistosomiasis transmission as a result of climate change. The
      results of these models can be very different when parameterised to different
      species of host snail, which have varying temperature preferences. Currently, the
      experimental data needed by these models are available for only a few species of
      snail. The choice of density-dependent functions can also affect model results,
      but the effects of increasing densities on Biomphalaria populations have only
      previously been investigated in artificial aquariums. METHODS: Laboratory
      experiments were conducted to estimate Biomphalaria sudanica mortality, fecundity
      and growth rates at ten different constant water temperatures, ranging from 13-32
      degrees C. Snail cages were used to determine the effects of snail densities on
      B. sudanica and B. stanleyi mortality and fecundity rates in semi-natural
      conditions in Lake Albert. RESULTS: B. sudanica survival and fecundity were
      highest at 20 degrees C and 22 degrees C respectively. Growth in shell diameter
      was estimated to be highest at 23 degrees C in small and medium sized snails, but
      the relationship between temperature and growth was not clear. The fecundity of
      both B. sudanica and B. stanleyi decreased by 72-75% with a four-fold increase in
      population density. Increasing densities four-fold also doubled B. stanleyi
      mortality rates, but had no effect on the survival of B. sudanica. CONCLUSIONS:
      The optimum temperature for fecundity was lower for B. sudanica than for
      previously studied species of Biomphalaria. In contrast to other Biomphalaria
      species, B. sudanica have a distinct peak temperature for survival, as opposed to
      a plateau of highly suitable temperatures. For both B. stanleyi and B. sudanica,
      fecundity decreased with increasing population densities. This means that snail
      populations may experience large fluctuations in numbers, even in the absence of
      any external factors such as seasonal temperature changes. Survival also
      decreased with increasing density for B. stanleyi, in contrast to B. sudanica and
      other studied Biomphalaria species where only fecundity has been shown to
      decrease.

PMID- 25388820
TI  - Pancreatic cancer genomics: where can the science take us?
AB  - The incidence of pancreatic ductal adenocarcinoma (PDAC) is steadily increasing
      and the annual death-to-incidence ratio approaches one. This is a figure that has
      not changed for several decades. Surgery remains the only chance of cure;
      however, only less than 20% of patients are amenable to operative resection.
      Despite successful surgical resection, the majority of the patients still succumb
      to recurrent metastatic disease. Therefore, there is an urgent need to develop
      novel therapeutic strategies and to better select patients for current therapies.
      In this review, we will discuss current management by highlighting the landmark
      clinical trials that have shaped current care. We will then discuss the
      challenges of therapeutic development using the current randomized-controlled
      trial paradigm when confronted with the molecular heterogeneity of PDAC. Finally,
      we will discuss strategies that may help to shape the management of PDAC in the
      near future. 

PMID- 25388821
TI  - Giant superior vena cava aneurysm after Fontan operation.

PMID- 25388822
TI  - Extracavitary cardiac carcinoid presenting with right ventricular outflow tract
      obstruction.

PMID- 25388823
TI  - Recent advances in acne pathogenesis: implications for therapy.
AB  - Acne pathogenesis is a multifactorial process that occurs at the level of the
      pilosebaceous unit. While acne was previously perceived as an infectious disease,
      recent data have clarified it as an inflammatory process in which
      Propionibacterium acnes and innate immunity play critical roles in propagating
      abnormal hyperkeratinization and inflammation. Alterations in sebum composition,
      and increased sensitivity to androgens, also play roles in the inflammatory
      process. A stepwise approach to acne management utilizes topical agents for mild
      to moderate acne (topical retinoid as mainstay +/- topical antibiotics) and
      escalation to oral agents for more resistant cases (oral antibiotics or hormonal
      agents in conjunction with a topical retinoid or oral isotretinoin alone for
      severe acne). Concerns over antibiotic resistance and the safety issues
      associated with isotretinoin have prompted further research into alternative
      medications and devices for the treatment of acne. Radiofrequency, laser, and
      light treatments have demonstrated modest improvement for inflammatory acne (with
      blue-light photodynamic therapy being the only US FDA-approved treatment).
      However, limitations in study design and patient follow-up render these
      modalities as adjuncts rather than standalone options. This review will update
      readers on the latest advancements in our understanding of acne pathogenesis and
      treatment, with emphasis on emerging treatment options that can help improve
      patient outcomes.

PMID- 25388824
TI  - Effect of D-psicose used as sucrose replacer on the characteristics of meringue.
AB  - Excessive intake of sugar-rich foods leads to metabolic syndrome. D-Psicose (Psi)
      not commonly found in nature, is noncalorie sweetener with a suppressive effect
      on the blood glucose level. Thus, Psi has the potential to be utilized as a
      sucrose (Suc) replacer in sugar-rich foods, including meringue-based
      confectionery (MBC). In this study, we investigated the effect of Psi on the
      physical and chemical properties of meringue. Meringue was made by whipping egg
      white and Suc (at a weight ratio of 1:1) and baking at 93  degrees C for 2 h.
      Thirty percent of the total weight of Suc was replaced with D-ketohexoses such as
      Psi, D-fructose, D-tagatose, and D-sorbose. The meringues containing D
      ketohexoses had higher specific volume than the meringue not containing D
      ketohexoses (Ct-meringue). Baking of meringue caused differences between Psi and
      the other D-ketohexose meringues. Meringue containing Psi (P30-meringue) had the
      highest breaking stress (7.00 * 10(5) N/m(2)) and breaking strain (4.40%),
      resulting in the crunchiest texture. In addition, P30-meringue also had the
      highest antioxidant activity (491.84 MUM TE/mg-meringue determined by ABTS
      method) and was the brownest due to a Maillard reaction occurring during baking.
      The replacement of Suc with Psi improved the characteristics of baked meringue.
      Thus, Psi was found to be useful in modifying the physical and chemical
      properties of MBC.

PMID- 25388825
TI  - Managing the phase separation in double emulsion by tuning amphiphilicity via a
      supramolecular route.
AB  - Double emulsion has attracted intense scientific investigation on account of its
      use in a wide range of applications. However, the process of its solidification
      is usually accompanied by the problem of uncontrollable phase separation. In this
      work, a supramolecular route is proposed to manage the phase separation in double
      emulsion. Different degrees of phase separations, from complete wetting to
      partial wetting and complete dewetting, have been achieved in an emulsion system
      consisting of P4VP-oleic acid. Partial wetting offers a strategy for generating
      polymer particles with controllable anisotropic structures. It is demonstrated
      that the amphiphilicity of polymer matrix, relying on the change of polymer-acid
      ratio or the chain length of aliphatic acid, is of vital importance for
      determining the degree of phase separation. A spreading and wetting theory is
      established to predict and explain the formation of partial wetting. 

PMID- 25388826
TI  - Molecular modeling of membrane responses to the adsorption of rotating
      nanoparticles: promoted cell uptake and mechanical membrane rupture.
AB  - Recently, a unique dynamic magnetic field was developed to induce the rotational
      movement of superparamagnetic iron oxide nanoparticles. This technique has been
      applied to remotely control both cellular internalization and apoptosis.
      Therefore, a thorough understanding of how a lipid membrane responds to the
      introduction of rotating NPs is quite important to promote the applications of
      this technique in a variety of biomedical area. Here, we performed Dissipative
      Particle Dynamics (DPD) simulations to systematically investigate the interaction
      mechanism between lipid membranes and rotating NPs. Two kinds of membrane
      responses are observed. One is the promoted cell uptake and the other is the
      mechanical membrane rupture. The promoting effect of NP rotation on the cell
      uptake is ascribed to the enhanced membrane monolayer protrusion, which can wrap
      the NP from the top side. Meanwhile, the rotating NP exerts a shearing force on
      the membrane. Accordingly, the membrane undergoes a local distortion around the
      NP. If the shearing force exceeds a critical value, the local membrane distortion
      develops into a mechanical rupture. A number of factors, like NP size, NP shape,
      ligand density and rotation speed, are critical in both of the above membrane
      responses. 

PMID- 25388827
TI  - Heart rate-corrected QT interval prolongation as a prognostic marker for 3-year
      survival in people with Type 2 diabetes undergoing above-ankle amputation.
AB  - AIM: To evaluate whether heart rate-corrected QT interval is a plausible
      prognostic factor for survival after major amputation in people with Type 2
      diabetes. METHODS: All people with Type 2 diabetes aged < 80 years who underwent
      a major amputation at two hospitals with multidisciplinary diabetic foot teams
      were evaluated and grouped according to whether their heart rate-corrected QT
      interval was  <=  or  > 440 ms. RESULTS: A total of 70 patients with a median age
      of 72 years were included in the study. During the 3 years of follow-up, 38
      patients (54%) died. Heart rate-corrected QT interval prolongation was present in
      51.4% of the patients and was strongly associated with 3-year mortality (73 vs
      36%; P < 0.001). In a Cox proportional hazard model, heart rate-corrected QT
      interval prolongation was the strongest independent risk factor for 3-year
      mortality [hazard ratio 2.20 (95% CI 1.11-4.38)]. Treatment with metformin seemed
      to have a protective effect [hazard ratio 0.22 (95% CI 0.05-0.94)]. CONCLUSIONS:
      The findings of the present study indicate that heart rate-corrected QT interval
      prolongation is associated with increased mortality in people with Type 2
      diabetes undergoing above-ankle amputation.

PMID- 25388828
TI  - Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a
      physiological method of increasing apnoea time in patients with difficult
      airways.
AB  - Emergency and difficult tracheal intubations are hazardous undertakings where
      successive laryngoscopy-hypoxaemia-re-oxygenation cycles can escalate to airway
      loss and the 'can't intubate, can't ventilate' scenario. Between 2013 and 2014,
      we extended the apnoea times of 25 patients with difficult airways who were
      undergoing general anaesthesia for hypopharyngeal or laryngotracheal surgery.
      This was achieved through continuous delivery of transnasal high-flow humidified
      oxygen, initially to provide pre-oxygenation, and continuing as post-oxygenation
      during intravenous induction of anaesthesia and neuromuscular blockade until a
      definitive airway was secured. Apnoea time commenced at administration of
      neuromuscular blockade and ended with commencement of jet ventilation, positive
      pressure ventilation or recommencement of spontaneous ventilation. During this
      time, upper airway patency was maintained with jaw-thrust. Transnasal Humidified
      Rapid-Insufflation Ventilatory Exchange (THRIVE) was used in 15 males and 10
      females. Mean (SD [range]) age at treatment was 49 (15 [25-81]) years. The median
      (IQR [range]) Mallampati grade was 3 (2-3 [2-4]) and direct laryngoscopy grade
      was 3 (3-3 [2-4]). There were 12 obese patients and nine patients were
      stridulous. The median (IQR [range]) apnoea time was 14 (9-19 [5-65]) min. No
      patient experienced arterial desaturation < 90%. Mean (SD [range]) post-apnoea
      end-tidal (and in four patients, arterial) carbon dioxide level was 7.8 (2.4 [4.9
      15.3]) kPa. The rate of increase in end-tidal carbon dioxide was 0.15 kPa.min(-1)
      . We conclude that THRIVE combines the benefits of 'classical' apnoeic
      oxygenation with continuous positive airway pressure and gaseous exchange through
      flow-dependent deadspace flushing. It has the potential to transform the practice
      of anaesthesia by changing the nature of securing a definitive airway in
      emergency and difficult intubations from a pressured stop-start process to a
      smooth and unhurried undertaking. 

PMID- 25388829
TI  - Cytoplasmic parafibromin/hCdc73 targets and destabilizes p53 mRNA to control p53
      mediated apoptosis.
AB  - The parafibromin/hCdc73 is a component of the PAFc, which controls RNA polymerase
      II-mediated general transcription. In parathyroid carcinoma and familial
      autosomal dominant hyperparathyroidism-jaw tumour (HPT-JT), hCdc73 mutations are
      heavily implicated, yet the underlying mechanism of its carcinogenic action is
      poorly understood. Here we demonstrate that hCdc73 specifically controls
      messenger RNA stability of p53 and p53-mediated apoptosis. hCdc73 is associated
      with mature p53 mRNA in the cytoplasm and facilitates its degradation.
      Cytoplasmic hCdc73 physically interacts with eEF1Bgamma and hSki8, and this
      interaction is required to bind and destabilize p53 mRNA. Furthermore, enhanced
      association of p53 mRNA with a cancer-driven hCdc73(K34Q) mutant was also
      observed. As a result, reduced p53 expression as well as enhanced cell
      proliferation was acquired in the hCdc73 (K34Q)-overexpressed cells. Altogether,
      our findings indicate that hCdc73 directly targets p53 mRNA to repress p53
      expression, and aberrant regulation of this interaction may lead to tumour
      progression. 

PMID- 25388830
TI  - [Challenges due to the demographic change: mental diseases today and tomorrow].

PMID- 25388831
TI  - [Respect for self-determination and use of coercion in the treatment of mentally
      ill persons: an ethical position statement of the DGPPN].
AB  - Respect for patient self-determination is a central ethical principle of medical
      care. Every person has the right to make decisions regarding his or her health
      autonomously, even if these decisions appear irrational to third parties. Free
      and informed consent is the necessary prerequisite for every diagnostic and
      therapeutic procedure. A patient's ability for self-determination is one
      requirement for valid consent. In illness, the ability for self-determination may
      be limited or absent in individual cases. An ethical dilemma arises if severely
      ill patients who are unable to make autonomous decisions put their health at
      significant risk and refuse medical procedures in this situation. While non
      treatment can be severely detrimental to health, forced procedures can result in
      traumatization and can damage the relationship of trust between the doctor and
      patient. The dilemma is intensified in cases of danger to others. In these
      difficult situations doctors, therapists and nursing staff require ethical
      guidance for the professional conduct. The primary objective thereby is to avoid
      coercion. For this purpose recommendations for medical practice are formulated
      that can reduce the use of forced procedures (e.g. de-escalation procedures,
      communication competency, clinical ethics counseling, treatment agreements and
      patient living wills) or if they are unavoidable, that allow them to be conducted
      in an ethically and legally appropriate way. Further and continued education must
      pay greater attention to this ethical objective; therefore, for ethical reasons
      adequate personnel, spatial and structural are vital in hospitals. 

PMID- 25388832
TI  - The role of the residential neighborhood in linking youths' family poverty
      trajectory to decreased feelings of safety at school.
AB  - Although disadvantaged youth are more likely to be victimized at school,
      victimization only partly explains their decreased feelings of safety at school.
      We applied a socioecological approach to test the hypotheses that the experience
      of poverty is associated with decreased feelings of safety at school, and that
      residential neighborhood features partly mediate the relationship between poverty
      and feeling less safe at school. This study draws on the Quebec Longitudinal
      Study of Child Development (QLSCD) which began in 1998 with a representative
      population-based cohort of 2,120 5-month old infants (49.1% female) and their
      primary caregiver. The study also includes measures of ego-centred residential
      neighborhood exposures (based on a 500 m circular buffer zone surrounding the
      family's residential postal code) derived from a spatial data infrastructure. We
      used latent growth modeling to estimate youth's family poverty trajectory from
      age 5 months to 13 years, and structural equation modeling to test our
      hypotheses. The results suggest that youth experiencing chronic and later
      childhood poverty felt less safe at school in part because they lived in
      neighborhoods that their parents described as being disorderly (e.g., demarked by
      the presence of garbage, drug use and groups of trouble-makers). These
      neighborhoods also tended to have less greenery (e.g., trees, parks) and more
      lone-parent households. Neighborhood features did not help explain the
      relationship between early-childhood poverty and feeling less safe at school. The
      findings suggest that targeting residential neighborhood features such as
      greenery and disorder could improve youth's felt safety at school, particularly
      for those experiencing chronic and later-childhood poverty.

PMID- 25388833
TI  - Chromosomally integrated human herpesvirus 6 in heart failure: prevalence and
      treatment.
AB  - AIMS: Human herpesvirus 6 (HHV-6) A and B are two betaherpesviruses that are
      associated with many conditions including roseola, drug-induced hypersensitivity
      syndrome, limbic encephalitis, and myocarditis. HHV-6 is integrated in the
      germline [chromosomically integrated HHV-6 (ciHHV-6)] in ~0.8% of the human
      population. To date, the prevalence, species distribution, and treatment
      responses of ciHHV-6 are unknown for cardiac patients. METHODS AND RESULTS: We
      determined the prevalence of HHV-6 and ciHHV-6 genotypes in 1656 endomyocardial
      biopsies of patients with persisting unexplained symptoms of heart failure.
      Infection of cardiac tissue was identified by nested PCR, electron microscopy,
      and immunohistochemistry. Virus load and mRNA levels were followed in ciHHV-6
      patients treated with ganciclovir. HHV-6 was detected in 273 of 1656 cardiac
      tissues (16.5%; HHV-6B, 98.2%, HHV-6A, 1.8%) by PCR. Nineteen of the 1656
      patients (1.1%) presented with persistently high HHV-6 copy numbers indicative of
      ciHHV-6. Sequencing confirmed ciHHV-6A in seven patients (36.8%) which was
      considerably higher than detected in non-ciHHV-6 patients. Inheritance was
      demonstrated in three selected families, confirming ciHHV-6 chromosomal
      integration by PCR and fluorescence in situ hybridization. HHV-6 reactivation and
      chromosomal integration were confirmed in peripheral blood mononuclear cells and
      heart tissue. Virus particles were identified in degenerating myocytes and
      interstitial cells. Antiviral treatment abolished viral mRNA and ameliorated
      cardiac symptoms. CONCLUSION: Virus replication in cardiac tissue of ciHHV-6
      heart failure patients suggests that ciHHV-6 reactivation causes persistence of
      unexplained heart failure symptoms. We demonstrated that antiviral treatment,
      effective in decreasing viral transcripts and clinical complaints of
      cardiomyopathies, is a new therapeutic option for ciHHV-6-associated diseases.

PMID- 25388835
TI  - In vitro cardioprotective effect of Wusen Erlian Granules through the inhibition
      of Coxsackievirus B3 replication.
AB  - Wusen Erlian Granules are a traditional Chinese medicine and we sought to
      determine the antiviral activity of Wusen Erlian Granules against Coxsackievirus
      B3 infection. First, cytotoxicity of Wusen Erlian Granules was determined in
      cultured cardiomyocytes isolated from day-old Wister rat pups. Later,
      cardiomyocytes were infected with Coxsackievirus B3 and the protective effect of
      Wusen Erlian Granules against cell injury was compared with that of ribavirin.
      Cell injury indicators including myoglobin, MB isozyme of Creatine Kinase, and
      cardiac Troponin were assessed by enzyme-linked immunosorbent assay (ELISA) and
      antiviral effect was assessed by MTT assay. We found that the 50 %-Toxic (TC50)
      and 50 %-Effective (EC50) concentrations of Wusen Erlian Granules were 394.05 and
      30.26 MUg/ml, respectively. Following infection of cardiomyocytes with
      Coxsackievirus B3, cell injury index of Wusen Erlian Granules, as determined by
      ELISA, was 125 MUg/ml which yielded significant protection from virus-induced
      cell damage. The antiviral activity of Wusen Erlian Granules i.e., therapeutic
      index in MTT assay was higher (13.02) than that of ribavirin (6.93). It was,
      therefore, concluded that the Wusen Erlian Granules exerted better antiviral
      effect than ribavirin using Coxsackievirus B3 in vitro infection model in terms
      of rat cardiomyocytes protection from virus-induced cell injury. 

PMID- 25388834
TI  - A protective role of ciglitazone in ox-LDL-induced rat microvascular endothelial
      cells via modulating PPARgamma-dependent AMPK/eNOS pathway.
AB  - Thiazolidinediones, the antidiabetic agents such as ciglitazone, has been proved
      to be effective in limiting atherosclerotic events. However, the underlying
      mechanism remains elucidative. Ox-LDL receptor-1 (LOX-1) plays a central role in
      ox-LDL-mediated atherosclerosis via endothelial nitric oxide synthase (eNOS)
      uncoupling and nitric oxide reduction. Therefore, we tested the hypothesis that
      ciglitazone, the PPARgamma agonist, protected endothelial cells against ox-LDL
      through regulating eNOS activity and LOX-1 signalling. In the present study, rat
      microvascular endothelial cells (RMVECs) were stimulated by ox-LDL. The impact of
      ciglitazone on cell apoptosis and angiogenesis, eNOS expression and
      phosphorylation, nitric oxide synthesis and related AMPK, Akt and VEGF signalling
      pathway were observed. Our data showed that both eNOS and Akt phosphorylation,
      VEGF expression and nitric oxide production were significantly decreased, RMVECs
      ageing and apoptosis increased after ox-LDL induction for 24 hrs, all of which
      were effectively reversed by ciglitazone pre-treatment. Meanwhile,
      phosphorylation of AMP-activated protein kinase (AMPK) was suppressed by ox-LDL,
      which was also prevented by ciglitazone. Of interest, AMPK inhibition abolished
      ciglitazone-mediated eNOS function, nitric oxide synthesis and angiogenesis, and
      increased RMVECs ageing and apoptosis. Further experiments showed that inhibition
      of PPARgamma significantly suppressed AMPK phosphorylation, eNOS expression and
      nitric oxide production. Ciglitazone-mediated angiogenesis and reduced cell
      ageing and apoptosis were reversed. Furthermore, LOX-1 protein expression in
      RMVECs was suppressed by ciglitazone, but re-enhanced by blocking PPARgamma or
      AMPK. Ox-LDL-induced suppression of eNOS and nitric oxide synthesis were largely
      prevented by silencing LOX-1. Collectively, these data demonstrate that
      ciglitazone-mediated PPARgamma activation suppresses LOX-1 and moderates
      AMPK/eNOS pathway, which contributes to endothelial cell survival and function
      preservation.

PMID- 25388836
TI  - Anatomical measurement and finite element study on screw channel parameter in
      percutaneous fixation of canulated screw for symphyseolysis.
AB  - To provide anatomical basement for symphyseolysis treatment with percutaneous
      fixation of canulated screw, through anatomical measurement on pubic symphysis
      and the surrounding tissues, and conduct the finite element studies on screw
      channel parameters. 20 cases of normal pelvic specimens from embalmed adult
      cadavers were taken to measure the anatomical parameter of bony remark of pubic
      symphysis and the space between spermatic cord (round ligament of the uterus) and
      pubic tubercle. Anatomical measurement results showed that the narrowest diameter
      of the superior ramus of pubis was 9.127 +/- 1.189 mm, distance between two pubic
      tubercles was 55.656 +/- 3.780 mm, thickness of the upper pubic symphysis was
      10.510 +/- 0.814 mm, and distance between upper and lower pubic symphysis was
      40.872 +/- 1.211 mm; the distance between round ligament of the uterus and pubic
      tubercle was 4.408 +/- 0.304 mm, and the distance between spermatic cord and
      pubic tubercle was 5.196 +/- 0.251 mm. The angle between canulated screw guide
      pin and horizontal plane was 8.342 +/- 2.152 degrees , the one between guide pin
      and coronal plane was 5.236 +/- 1.612 degrees , and the distance from entry point
      to the outer edge of pubic tubercle was 10.023 +/- 1.245 mm, which was measured
      by Mimics software. Percutaneous surgery at horizontal position was simulated on
      cadaver. And the screw was correctly placed in postoperative imaging examination.
      According to the anatomical data and finite element studies of screw channel
      parameter in percutaneous fixation of canulated screw for symphyseolysis, the
      method can improve the accuracy of screw placement and reduce complications.

PMID- 25388837
TI  - Anti-inflammatory Mechanism of Bone Marrow Mesenchymal Stem Cell Transplantation
      in Rat Model of Spinal Cord Injury.
AB  - To explore the effect of bone marrow mesenchymal stem cell (BMSC) transplantation
      on the levels of toll-like receptor 4 (TLR4), interleukin-1beta (IL-1beta), and
      tumor necrosis factor (TNF-alpha) in spinal cord tissue of rat model of spinal
      cord injury (SCI). BMSCs from 4-week-old male SD rats were isolated, cultured,
      and characterized after three generations using specific surface markers CD34 and
      CD44. Fifty four SD male rats were divided into sham group, model group, and cell
      transplantation group (18 rats each group). SCI model was generated using an
      improved Allen's method. Rats in cell transplantation group were treated with
      BMSCs in caudal vein. Rats were sacrificed at 24 h, 72 h, and 7 d post-injury,
      and spinal cord tissues were taken out for detection of IL-1beta and TNF-alpha
      tissue content by enzyme-linked immunosorbent assay. IL-1beta and TNF-alpha mRNA
      expression was evaluated by qPCR and TLR4 protein expression was analyzed by
      Western blotting. IL-1beta and TNF-alpha protein levels, as well as IL-1beta, TNF
      alpha mRNA, and TLR4 expression were significantly increased in rats with
      established SCI, and reached its peak in spinal cord tissues at 72 h after the
      initial injury (p < 0.01 comparing to sham group). BMSC transplantation resulted
      in significant decrease in IL-1beta and TNF-alpha tissue content, as well as IL
      1beta, TNF-alpha mRNA, and TLR4 expression as compared with model group (p <
      0.01). BMSCs may alleviate the damaging effect of spinal cord inflammation by
      weakening TLR4-mediated signaling pathways and reducing tissue content of IL
      1beta and TNF-alpha.

PMID- 25388838
TI  - Catalpol Inhibited the Proliferation of T24 Human Bladder Cancer Cells by
      Inducing Apoptosis Through the Blockade of Akt-Mediated Anti-apoptotic Signaling.
AB  - Catalpol is an iridoid glucoside extracted from the traditional Chinese medicinal
      plant called Rehmannia glutinosa, and it is reported to possess a variety of
      pharmacological activities. The goal of this research was to explore the effect
      of catalpol on the human bladder cancer cells T24. The cells were treated for
      different durations with various concentrations of catalpol. Then the viability,
      mobility, and invasiveness of the cells were determined by MTT assay and flow
      cytometry, respectively. Catalpol was found to significantly suppress the
      proliferation, migration, and invasiveness of T24 bladder cancer cells in a dose-
      and time-dependent manner. The results also revealed that catalpol promoted
      apoptosis and caused the cell-cycle arrest at G2/M phase. Furthermore, the
      catalpol-mediated apoptosis was found to involve the modulation of PI3K/Akt
      pathway and inhibit the expression of anti-apoptotic B cell lymphoma-2 (Bcl-2)
      family proteins. Also, the expressions of Bcl-2 proapoptotic effectors, Bcl-2
      associated X protein, and Bcl-2 associated death promoter were up-regulated in
      the cells treated with catalpol. The enzymes involved in the ultimate process of
      apoptosis, active caspase-3 and poly ADP ribose polymerase were elevated, and the
      latter was observed to be cleaved, indicating that catalpol-accelerated cell
      apoptosis involved a caspase-dependent pathway. These results suggest that
      catalpol might serve to be a promising therapeutic agent for the treatment of
      human bladder cancer. 

PMID- 25388839
TI  - Pirenzepine Inhibits Myopia in Guinea Pig Model by Regulating the Balance of MMP
      2 and TIMP-2 Expression and Increased Tyrosine Hydroxylase Levels.
AB  - In this study, we investigated the effects and mechanism of action of pirenzepine
      in a guinea pig model of myopia induced by exposure to monochromatic light. It
      was observed that pirenzepine inhibited the increase of diopter and extension of
      ocular axial length. Immunohistochemistry staining showed that the number of
      tyrosine hydroxylase (TH)-positive cells in pirenzepine group was significantly
      higher compared to the other treatment groups pointing to a highly positive
      correlation between TH expression levels and the diopter and axial length change.
      RT-PCR analysis further showed that pirenzepine treatment reduced the expression
      of matrix metalloproteinase (MMP-2) and enhanced the expression of tissue
      inhibitors of metalloproteinase (TIMP-2) compared to the other treatment and
      control groups. To conclude, we demonstrate that pirenzepine may improve the
      prognosis of monochromatic light-induced myopia in guinea pigs, possibly by both
      regulating the balance of MMP-2 and TIMP-2 in sclera and increasing the TH
      expression in retina. 

PMID- 25388840
TI  - Influence of Val108/158Met COMT Gene Polymorphism on the Efficacy of Modified
      Electroconvulsive Therapy in Patients with Treatment Resistant Depression.
AB  - Depression is a common emotional disorder associated with increased risk of
      suicide and rate of disability. In this double-blinded control study, we tested
      the efficacy of modified electroconvulsive therapy (MECT) in patients with
      treatment resistant depression (TRD) using the Hamilton Depression Rating Scale
      for Depression (HAMD). The total scores of HAMD were found to be significantly
      decreased after the treatment. The genotyping of catechol-O-methyltransferase
      (COMT) was carried out with polymerase chain reaction-based testing. Our results
      demonstrated that frequency of mutant COMT alleles in TRD patients was
      significantly higher than that of the controls indicating a correlation of the
      enzyme genotype to the occurrence of TRD. Moreover, the patients homozygous for
      wild-type COMT gene (G/G) were evidenced to be more sensitive to MECT treatment
      than those with an heterozygous mutant genotype (A/G). 

PMID- 25388841
TI  - Revealing the Strong Functional Association of adipor2 and cdh13 with adipoq: A
      Gene Network Study.
AB  - In the present study, we have analyzed functional gene interactions of
      adiponectin gene (adipoq). The key role of adipoq is in regulating energy
      homeostasis and it functions as a novel signaling molecule for adipose tissue.
      Modules of highly inter-connected genes in disease-specific adipoq network are
      derived by integrating gene function and protein interaction data. Among twenty
      genes in adipoq web, adipoq is effectively conjoined with two genes: Adiponectin
      receptor 2 (adipor2) and cadherin 13 (cdh13). The functional analysis is done via
      ontological briefing and candidate disease identification. We observed that the
      highly efficient-interlinked genes connected with adipoq are adipor2 and cdh13.
      Interestingly, the ontological aspect of adipor2 and cdh13 in the adipoq network
      reveal the fact that adipoq and adipor2 are involved mostly in glucose and lipid
      metabolic processes. The gene cdh13 indulge in cell adhesion process with adipoq
      and adipor2. Our computational gene web analysis also predicts potential
      candidate disease recognition, thus indicating the involvement of adipoq,
      adipor2, and cdh13 with not only with obesity but also with breast cancer,
      leukemia, renal cancer, lung cancer, and cervical cancer. The current study
      provides researchers a comprehensible layout of adipoq network, its functional
      strategies and candidate disease approach associated with adipoq network. 

PMID- 25388842
TI  - Transplantation of iPSc Restores Cardiac Function by Promoting Angiogenesis and
      Ameliorating Cardiac Remodeling in a Post-infarcted Swine Model.
AB  - Induced pluripotent stem cells (iPSc) hold significant promise for the
      development of cardiac regenerative therapy for myocardial infarction (MI).
      However, preclinical optimization and validation of large-animal models will be
      required before iPSc used clinically. Therefore, we aim to investigate the
      therapeutic potential of iPSc transplantation for MI and relative mechanisms in a
      post-infarcted swine model. Left anterior descending coronary artery was balloon
      occluded after percutaneous transluminal angiography to generate MI (60-min no
      flow ischemia). Animals were then divided into Sham, PBS control, and iPS
      experimental groups. The cardiac function and LV structural were assessed by dual
      source computed tomography. Terminal deoxynucleotidyl nick end labeling,
      histology, and immunofluorescence were used to examine the effect of transplanted
      iPS cells on apoptosis, fibrosis, and hypertrophy. At 6 weeks, LV structural
      abnormality and cardiac dysfunction were less pronounced in iPSc group than in
      PBS group, and these improvements were accompanied by reduction of scar size.
      iPSc transplantation was associated with significant increase of vascular density
      and reduced myocardial apoptosis in the border zone of infarction, which was
      accompanied by the reduction in fibrosis degree. Moreover, proangiogenic and
      antiapoptotic factors were increased significantly in iPS group compared with PBS
      group. Cardiomyocyte hypertrophy was significantly attenuated by iPSc
      transplantation. In conclusion, these results suggested that transplantation of
      iPSc may result in functional recovery by promoting angiogenesis, inhibiting
      apoptosis, and ameliorating cardiac remodeling. This proof of concept study may
      provide a basis for an autologous iPSc-based therapy of MI.

PMID- 25388844
TI  - Gene and Protein Network Analysis of AmpC beta Lactamase.
AB  - AmpC beta-lactamase is a cephalosporinase, which exhibits resistance against all
      existing beta-lactam antibiotics except carbapenems. Their occurrence in many
      bacterial pathogens poses a threat to public health and is a growing concern in
      the medical world. The ampC gene is highly inducible in the presence of beta
      lactam antibiotics and can be expressed in high levels due to mutation. This
      inducible expression is regulated by several functional genes. Several studies on
      functional relationship of these genes and its resistance mechanisms are carried
      out but it still lacks comprehensible evidences. Thus, in our current study, we
      used computational gene networks to analyze ampC gene. Based on its interaction
      type, co-expression, Gene Ontology, and text mining, a functional interaction
      network is constructed. Around 247 functional genes in 15 different bacterial
      genus have a functional association with ampC gene. It is predicted that 19.8%
      ampD, 13.3% frdD, 8.5% gcvA, 2.4% ampR, and 55.7% of other functional partners
      are associated with ampC gene. Our present study provides a glimpse about the
      functional gene network of ampC gene and also provides the integrated evidence
      for ampC gene in regulating the beta-lactamase production and its role in
      antibiotic resistance.

PMID- 25388843
TI  - Osteoconductivity of Complex Biomaterials Assayed by Fluorescent-Engineered
      Osteoblast-like Cells.
AB  - Biomaterials employed for the bone regeneration can be assayed for specific
      features such as osteoconductivity and gene expression. In this study, the
      composite HA/collagen/chondroitin-sulfate biomaterial was investigated using an
      engineered human cell line, named Saos-eGFP. This cell line, a green fluorescent
      engineered human osteoblast-like cell, was employed as a cellular model for the
      in vitro study of biomaterial characteristics. The cytotoxicity was indirectly
      evaluated by fluorescence detection, osteoconductivity was assayed both by
      fluorescence and electron microscope analysis as well as cell morphology, whereas
      the RT-PCR technique was employed to assay gene expression. Saos-eGFP cells
      viability detection after 24 and 96 h of incubation showed that biomaterial
      enables the adhesion and proliferation of seeded cells as well as that of the
      plastic surface, the control. Fluorescence and scanning electron microscopy (SEM)
      analyses indicated that Saos-eGFP cells were homogeneously distributed on the HA
      granule surfaces, exhibiting cytoplasmic bridges, and were localized on the
      collagen-chondroitin sulfate extra-cellular matrix. An expression analysis of
      specific genes encoding for differentiation markers, showed that biomaterial
      assayed did not alter the osteogenic pathway of the Saos-eGFP cell line. Our
      assays confirm the cytocompatibility of this biomaterial, suggesting an
      osteoconductive capacity mediated by its chemical contents. We showed that the
      Saos-eGFP cellular model is suitable for in vitro biomaterial assays, and more
      specifically for assessing osteoconductivity. This result suggests that the
      cytocompatibility and osteoconductive features of the biomaterial assayed as bone
      substitute, could have a positive downstream effect on implant osteo-integration.

PMID- 25388845
TI  - Conformational Preferences of Modified Nucleoside 5-Taurinomethyluridine,
      taum(5)U Occur at 'wobble' 34th Position in the Anticodon Loop of tRNA.
AB  - Conformational preferences of hypermodified nucleoside 5-taurinomethyluridine 5'
      monophoshate 'p-taum(5)U' (-CH2-NH2(+)-CH2-CH2-SO3(-)) have been investigated
      using semi-empirical RM1 method. Automated geometry optimization using ab initio
      molecular orbital HF-SCF (6-31G**) and DFT (B3LYP/6-31G**) calculations have also
      been made to compare the salient features. The RM1 preferred most stable
      conformation of 'p-taum(5)U' has been stabilized by hydrogen bonding interactions
      between O(11a)...HN(8), O1P(34)...HN(8), and O1P(34)...HC(10). Another
      conformational study of 5-taurinomethyluridine side chain has also been performed
      in context of anticodon loop bases of E. coli tRNA(Leu). The atom O(11a) of
      taum(5)U(34) side chain interacts with adenosine (A35) as well as ribose
      phosphate backbone which might provide structural stability to the anticodon
      loop. The glycosyl torsion angle of taum(5)U retains 'anti'-conformation. The
      solvent accessible surface area calculations revealed the role of taum(5)U in
      tRNA(Leu) anticodon loop. MD simulation results are found in agreement with RM1
      preferred stable structure. The MEPs calculations of taum(5)U(34):G3 model show
      unique potential tunnels between the hydrogen bond donor and acceptor atoms as
      compared to taum(5)U(34):A3 model. Thus, these results could pave the way to
      understand the role of taum(5)U(34) to recognize UUG/UUA codons at atomic level
      in the mitochondrial disease, MELAS.

PMID- 25388846
TI  - Bioinformatic Analysis of GJB2 Gene Missense Mutations.
AB  - Gap junction beta 2 (GJB2) gene is the most commonly mutated connexin gene in
      patients with autosomal recessive and dominant hearing loss. According to Ensembl
      (release 74) database, 1347 sequence variations are reported in the GJB2 gene and
      about 13.5% of them are categorized as missense SNPs or nonsynonymous variant.
      Because of the high incidence of GJB2 mutations in hearing loss patients,
      revealing the molecular effect of GJB2 mutations on protein structure may also
      provide clear point of view regarding the molecular etiology of deafness. Hence,
      the aim of this study is to analyze structural and functional consequences of all
      known GJB2 missense variations to the Cx26 protein by applying multiple
      bioinformatics methods. Two-hundred and eleven nonsynonymous variants were
      collected from Ensembl release 74, Leiden Open Variation Database (LOVD) and The
      Human Gene Mutation Database (HGMD). A number of bioinformatic tools were
      utilized for predicting the effect of GJB2 missense mutations at the sequence,
      structural, and functional levels. Some of the mutations were found to locate
      highly conserved regions and have structural and functional properties. Moreover,
      GJB2 mutations were also found to affect Cx26 protein at the molecular level via
      loss or gain of disorder, catalytic site, and post-translational modifications,
      including methylation, glycosylation, and ubiquitination. Findings, presented
      here, demonstrated the application of bioinformatic algorithms to predict the
      effects of mutations causing hearing impairment. I expect, this type of analysis
      will serve as a start point for future experimental evaluation of the GJB2 gene
      mutations and it will also be helpful in evaluating other deafness-related gene
      mutations.

PMID- 25388847
TI  - Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based
      Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer.
AB  - The aim was to determine changes in dihydropyrimidine dehydrogenase (DPD) and
      thymidylate synthase (TS) mRNAs in the blood of advanced gastric cancer (AGC)
      patients to see whether these enzymes affected the patients' response to S-1
      based chemotherapy and prognosis. For this purpose, pretreatment DPD/TS mRNA
      expressions were determined in 40 AGC patients using RT-PCR. The patients were
      then administered with S-1-based regimen (S-1 + cisplatin) and toxicities were
      recorded. The relationship between the DPD/TS mRNA expressions and the
      chemotherapy response, drug resistance, and prognosis was analyzed. The data show
      that DPD mRNA expression correlated significantly with Lauren type while TS mRNA
      expression correlated with distant metastasis. Patients with higher DPD and/or TS
      mRNA expression(s) showed poor response, while those with low DPD mRNA expression
      showed better response to the chemotherapy. Pooled analysis showed that the
      patients with low DPD/TS mRNA expressions had better therapeutic response. The
      incidence of bone marrow suppression, diarrhea, and oral mucositis was high in
      patients with low DPD mRNA expression. Median overall survival (OS) in 40
      patients was 13.5 months. It was 17 months for low and 10 months for high DPD (P
      = 0.044) and TS mRNA expression (P = 0.047). Pooled analysis showed that the
      patients with both low DPD/TS mRNA expressions had longer OS (P = 0.001). In
      conclusion, the detection of DPD and/or TS mRNA expression can be used to predict
      the response to S-1-based chemotherapy, drug resistance, and prognosis in AGC
      patients as well as to help guide the individualized treatment of gastric cancer.

PMID- 25388848
TI  - RNAi Knockdown of Hypoxia-Inducible Factor-1alpha Decreased the Proliferation,
      Migration, and Invasion of Hypoxic Hepatocellular Carcinoma Cells.
AB  - The obstruction of hepatic arterial blood flow results in tumor tissue hypoxia
      and elevated expression of hypoxia-inducible factor-1alpha (HIF-1alpha). Our
      study evaluated whether lentivirus-mediated short interference RNA against HIF
      1alpha inhibits proliferation, invasion, and migration of hepatocellular
      carcinoma (HCC) cells under hypoxia. RNA interference knockdown of HIF-1alpha was
      achieved by HIF-1alpha-directed lentiviral shRNA, in a rat HCC cell line cultured
      under hypoxia condition for varying length of times. The expression levels of HIF
      1alpha and vascular endothelial growth factor were examined using reverse
      transcription polymerase chain reaction and western blot analyses. Cell
      proliferation, migration, and invasion were measured by cell viability, transwell
      migration, and invasion assays, respectively. Inhibition of HIF-1alpha expression
      by shRNA suppressed vascular endothelial growth factor mRNA and protein levels
      under both normoxia and hypoxia. It also suppressed cell migration and invasion,
      which were enhanced under hypoxic conditions. RNAi knockdown of HIF-1alpha
      further suppressed hypoxia-mediated inhibition of the cell proliferation. These
      data suggest that shRNA of HIF-1alpha could antagonize the hypoxia-mediated
      increase in hepatic cancer cell migration and invasion, and synergize with
      hypoxia to inhibit the cell proliferation in HCC cells. 

PMID- 25388849
TI  - Increased Expression of p-Akt correlates with Chronic Allograft Nephropathy in a
      Rat Kidney Model.
AB  - Chronic allograft nephropathy (CAN) is the most common cause of chronic graft
      dysfunction leading to graft failure, our study investigates the expression and
      significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher
      (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals
      were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal
      function and histopathology. Phosphorate Akt (p-Akt) protein expression was
      determined by Western blot and immunohistological assays. Our data show that 24-h
      urinary protein excretion in CAN rats increased significantly at week 16 as
      compared with F344/LEW controls. Allografts got severe interstitial infiltration
      of mononuclear cells at week 4 and week 8, but it was degraded as the time went
      on after week 16. Allografts markedly presented with severe interstitial fibrosis
      (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in
      rat kidneys with CAN, and the increase became more significant over time after
      transplantation. p-Akt expression correlated significantly with 24-h urinary
      protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells
      infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It
      was concluded that p-Akt overexpression might be the key event that involved
      mononuclear cells infiltration and vascular SMCs migration at early stage, and IF
      and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.

PMID- 25388850
TI  - Construction and Application of a Refined Hospital Management Chain.
AB  - Gaining large scale success was quite common in the later period of
      industrialization for hospitals in China. Today, Chinese hospital management face
      such problems as service inefficiency, high human resources cost, and low rate of
      capital use. This study analyzes the refined management chain of the Wuxi No. 2
      People's Hospital. This consists of six gears namely "organizational structure,
      clinical practice, outpatient service, medical technology, and nursing care and
      logistics" used to achieve maximum scale and benefits. The gears are based on
      "flat management system targets, chief of medical staff, centralized outpatient
      service, intensified medical examinations, vertical nursing management and
      socialized logistics". The hospital took innovative measures. The "one doctor-one
      patient-one clinic" was well accepted; "one dispensary" shorten the waiting time
      by 20 min. The 168 rear service hot line "made patients' lives easier; and a red
      wrist ribbon" for seriously ill patient was implemented to prioritize medical
      treatment. The core concepts of refined hospital management are optimizing flow
      process, reducing waste, improving efficiency, saving costs, and taking good care
      of patients as most important.

PMID- 25388851
TI  - Immunoglobulin heavy variable (IGHV) genes and alleles: new entities, new names
      and implications for research and prognostication in chronic lymphocytic
      leukaemia.
AB  - Nuext generation sequencing studies in Homo sapiens have identified novel
      immunoglobulin heavy variable (IGHV) genes and alleles necessitating changes in
      the international ImMunoGeneTics information system (IMGT) GENE-DB and reference
      directories of IMGT/V-QUEST. In chronic lymphocytic leukaemia (CLL), the somatic
      hypermutation (SHM) status of the clonotypic rearranged IGHV gene is strongly
      associated with patient outcome. Correct determination of this parameter strictly
      depends on the comparison of the nucleotide sequence of the clonotypic rearranged
      IGHV gene with that of the closest germline counterpart. Consequently, changes in
      the reference directories could, in principle, affect the correct interpretation
      of the IGHV mutational status in CLL. To this end, we analyzed 8066 productive IG
      heavy chain (IGH) rearrangement sequences from our consortium both before and
      after the latest update of the IMGT/V-QUEST reference directory. Differences were
      identified in 405 cases (5 % of the cohort). In 291/405 sequences (71.9 %),
      changes concerned only the IGHV gene or allele name, whereas a change in the
      percent germline identity (%GI) was noted in 114/405 (28.1 %) sequences; in
      50/114 (43.8 %) sequences, changes in the %GI led to a change in the mutational
      set. In conclusion, recent changes in the IMGT reference directories affected the
      interpretation of SHM in a sizeable number of IGH rearrangement sequences from
      CLL patients. This indicates that both physicians and researchers should consider
      a re-evaluation of IG sequence data, especially for those IGH rearrangement
      sequences that, up to date, have a GI close to 98 %, where caution is warranted. 

PMID- 25388852
TI  - Evaluation of neonatal Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene
      polymorphisms in HBV intrauterine transmission susceptibility.
AB  - To investigate whether single nucleotide polymorphisms (SNPs) in Toll-like
      receptors (TLRs) 3 and 9 affect the susceptibility of hepatitis B virus (HBV)
      intrauterine transmission, we genotyped 399 neonates for TLR3 (c.1377C/T)
      [rs3775290] and TLR9 (G2848A) [rs352140] using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). A femoral venous blood
      sample was obtained from these subjects. Hepatitis B surface antigen (HBsAg) and
      hepatitis B e antigen (HBeAg) were measured using chemiluminescence immunoassay
      kits and hepatitis B virus DNA (HBV DNA) levels were determined by fluorescence
      quantitative PCR assay. Our results showed that when adjusting for maternal
      HBeAg, maternal HBV DNA and mode of delivery, allele 'T' for SNP c.1377C/T was
      significantly associated with HBV intrauterine transmission susceptibility
      [adjusted OR (aOR) 0.55, 95% confidence interval (CI) 0.34-0.91, P = 0.020] and
      the TT genotype decreased the risk of HBV intrauterine transmission (aOR 0.28,
      95% CI 0.09-0.91, P = 0.033). Allele 'A' for SNP G2848A was significantly
      associated with HBV intrauterine transmission susceptibility (aOR 0.62, 95% CI
      0.39-1.00, P = 0.048) and the GA genotype protected neonates from HBV
      intrauterine transmission (aOR 0.45, 95% CI 0.22-0.93, P = 0.031). The TLR3
      (c.1377C/T) and TLR9 (G2848A) polymorphisms may be relevant for HBV intrauterine
      transmission susceptibility, although the reduction in risk to HBV intrauterine
      transmission is modest and the biological mechanism of the observed association
      merits further investigation.

PMID- 25388853
TI  - Expression of key executioner of apoptosis caspase-3 in periodontal health and
      disease.
AB  - AIM: A highly-regulated form of programmed cell death is apoptosis, and its
      perturbation has been associated with periodontal disease. Caspase-3 is one of
      the key executioners of apoptosis. The present study was designed to evaluate and
      correlate the levels of caspase-3 in gingival crevicular fluid (GCF) and serum in
      participants with clinically-healthy periodontium, gingivitis, and chronic
      periodontitis (CP). METHODS: Forty-four sex- and age-matched participants were
      enrolled into three groups based on clinical parameters. Group 1 participants had
      clinically-healthy periodontium, group 2 participants had gingivitis, and group 3
      participants had CP. GCF and serum samples were collected to evaluate the levels
      of caspase-3. RESULTS: The mean caspase-3 concentration in GCF and serum was
      highest in group 3, followed by group 2, and was significantly correlated with
      gingival index, probing depth (PD), and clinical attachment level (CAL).
      CONCLUSION: GCF and the serum concentration of caspase-3 proportionally increases
      with the progression of periodontal disease, that is, gingival inflammation, PD,
      and CAL.

PMID- 25388854
TI  - More a finger than a nose: the trigeminal motor and sensory innervation of the
      Schnauzenorgan in the elephant-nose fish Gnathonemus petersii.
AB  - The weakly electric fish Gnathonemus petersii uses its electric sense to actively
      probe the environment. Its highly mobile chin appendage, the Schnauzenorgan, is
      rich in electroreceptors. Physical measurements have demonstrated the importance
      of the position of the Schnauzenorgan in funneling the fish's self-generated
      electric field. The present study focuses on the trigeminal motor pathway that
      controls Schnauzenorgan movement and on its trigeminal sensory innervation and
      central representation. The nerves entering the Schnauzenorgan are very large and
      contain both motor and sensory trigeminal components as well as an electrosensory
      pathway. With the use of neurotracer techniques, labeled Schnauzenorgan
      motoneurons were found throughout the ventral main body of the trigeminal motor
      nucleus but not among the population of larger motoneurons in its rostrodorsal
      region. The Schnauzenorgan receives no motor or sensory innervation from the
      facial nerve. There are many anastomoses between the peripheral electrosensory
      and trigeminal nerves, but these senses remain separate in the sensory ganglia
      and in their first central relays. Schnauzenorgan trigeminal primary afferent
      projections extend throughout the descending trigeminal sensory nuclei, and a few
      fibers enter the facial lobe. Although no labeled neurons could be identified in
      the brain as the trigeminal mesencephalic root, some Schnauzenorgan trigeminal
      afferents terminated in the trigeminal motor nucleus, suggesting a monosynaptic,
      possibly proprioceptive, pathway. In this first step toward understanding
      multimodal central representation of the Schnauzenorgan, no direct
      interconnections were found between the trigeminal sensory and electromotor
      command system, or the electrosensory and trigeminal motor command. The pathways
      linking perception to action remain to be studied.

PMID- 25388856
TI  - [Influence of body mass index on histopathological and intraoperative criteria in
      a consecutive series of patients after robotic-assisted radical prostatectomy].
AB  - BACKGROUND: In various studies it has been shown that obesity enhances the risk
      for a unfavorable pathological tumour stages, higher Gleason scores (GS),
      positive surgical margins (PSM), and certain perioperative parameters (higher
      blood loss, higher length of surgery, higher complication rates) after radical
      prostatectomy. However, for robot-assisted radical prostatectomy (RARP) there are
      only a few studies addressing this topic with partially conflicting results.
      Furthermore, none of these studies actually represents the clinical practice
      pattern as performed in a European centre. MATERIAL AND METHODS: Beside further
      clinical and histopathological parameters, also body mass index (BMI) of patients
      undergoing RARP was recorded. The following categories were registered: BMI of <
      25 kg/m2, >= 25-29.9 kg/m2, and >= 30 kg/m2 defined as normal weight, overweight,
      and obesity, respectively. The potential correlation between BMI on the one hand
      and various criteria of aggressive tumour biology and specific perioperative
      parameters on the other hand has been examined on univariate and multivariable
      analyses. RESULTS: 22.8% (n=79), 59% (n=204), and 18.2% (n=63) of patients of the
      study group presented with normal weight, overweight, and obesity, respectively.
      Based on the results of various multivariable regression models there was no
      significant influence of obesity on pathological tumour stage, pN category,
      undifferentiated tumour growth (>= GS7b), upgrading, or PSM rates. Furthermore,
      obese patients showed a significantly higher intraoperative blood loss and a
      higher length of surgery, which, however, did not result in a higher rate of
      grade 3a/b complications according to Clavien-Dindo classification after 90 days.
      CONCLUSIONS: In the present series of consecutive patients undergoing RARP there
      was no evidence for a more aggressive tumour biology or a higher complication
      rate in obese patients.

PMID- 25388855
TI  - Multidrug-resistant Gram-negative bacteria in solid organ transplant recipients
      with bacteremias.
AB  - Bloodstream infections (BSIs) remain as life-threatening complications and are
      associated with significant morbidity and mortality among solid organ transplant
      (SOT) recipients. Multidrug-resistant (MDR) Gram-negative bacteria can cause
      serious bacteremias in these recipients. Reviews have aimed to investigate MDR
      Gram-negative bacteremias; however, they were lacking in SOT recipients in the
      past. To better understand the characteristics of bacteremias due to MDR Gram
      negative bacteria, optimize preventive and therapeutic strategies, and improve
      the outcomes of SOT recipients, this review summarize the epidemiology, clinical
      and laboratory characteristics, and explores the mechanisms, prevention, and
      treatment of MDR Gram-negative bacteria. 

PMID- 25388857
TI  - The shortened spinal cord in tetraodontiform fishes.
AB  - In teleosts, the spinal cord generally extends along the entire vertebral canal.
      The Tetraodontiformes, in which the spinal cord is greatly reduced in length with
      a distinct long filum terminale and cauda equina, have been regarded as an
      aberration. The aims of this study are: 1) to elucidate whether the spinal cord
      in all tetraodontiform fishes shorten with the filum terminale, and 2) to
      describe the gross anatomical and histological differences in the spinal cord
      among all families of the Tetraodontiformes. Representative species from all
      families of the Tetraodontiformes, and for comparison the carp as a common
      teleost, were investigated. In the Triacanthodidae, Triacanthidae, and
      Triodontidae, which are the more ancestral taxa of the Tetraodontiformes, the
      spinal cord extends through the entire vertebral canal. In the Triacanthidae and
      Triodontidae, the caudal half or more spinal segments of the spinal cord,
      however, lack gray matter and consist largely of nerve fibers. In the other
      tetraodontiform families, the spinal cord is shortened forming a filum terminale
      with the cauda equina, which is prolonged as far as the last vertebra. The
      shortened spinal cord is divided into three groups. In the Ostraciidae and
      Molidae, the spinal cord tapers abruptly at the cranium or first vertebra forming
      a cord-like filum terminale. In the Monacanthidae, Tetraodontidae, and
      Diodontidae, it abruptly flattens at the rostral vertebrae forming a flat filum
      terminale. The spinal cord is relatively longer in the Monacanthidae than that in
      the other two families. It is suggested by histological features of the flat
      filum terminale that shortening of the spinal cord in this group progresses in
      order of the Monacanthidae, Tetraodontidae, and Diodontidae. In the Balistidae
      and Aracanidae, the cord is relatively long and then gradually decreased in dorso
      ventral thickness.

PMID- 25388858
TI  - Social competence following neonatal and childhood stroke.
AB  - BACKGROUND: Social functioning encompasses a range of important skills that an
      individual uses to interact with the social world. Previous studies suggest that
      social functioning (outcomes) may be impaired after childhood stroke, but
      research is limited. AIMS: We examined the following: (1) the effect of ischemic
      stroke upon social outcomes in children; (2) the correlation of cognitive
      abilities and problem behaviors with social outcomes; and (3) the role of infarct
      characteristics as predictors of social outcomes. METHODS: We conducted an
      observational case-controlled study to compare children with neonatal or
      childhood onset stroke and controls with chronic asthma. Neurological deficits
      were measured with the Pediatric Stroke Outcome Measure. Cognitive abilities,
      problem behavior, adaptive behavior, and social outcomes were assessed with
      standardized measures. RESULTS: Overall stroke cases were impaired in several
      areas of adaptive behaviors but not in cognitive ability, problem behaviors, or
      social outcomes. Children with more severe neurological deficits had impairments
      in a range of adaptive behaviors, social adjustment, and social participation.
      Impaired cognitive ability and more problem behaviors correlated with impaired
      social adjustment, particularly in stroke cases. Larger infarcts correlated with
      greater neurological impairment, lower IQ, and poorer social participation.
      CONCLUSIONS: Stroke can result in impaired adaptive and social functioning
      without apparent deficits in IQ or behavior. Infarct size, residual neurological
      deficits, impaired cognitive ability, and problem behaviors increase the risk for
      poor social adjustment and participation. These findings can help the clinician
      anticipate impaired social functioning after pediatric stroke, which is important
      because age-specific treatments are available.

PMID- 25388859
TI  - The role of sublingual sufentanil nanotabs for pain relief.
AB  - INTRODUCTION: The authors discuss a novel patient controlled analgesia system
      utilizing a preprogrammed device that delivers a small submucosal tablet of
      sufentanil. AREAS COVERED: This submucosal sufentanil system is not yet
      commercially available. A literature review of the current patient controlled
      analgesia systems and current information of this device are discussed. EXPERT
      OPINION: This novel device has the potential to enhance patient safety as it is
      preprogrammed and delivers a standard dose of sufentanil, a rapidly acting opioid
      devoid of active metabolites.

PMID- 25388860
TI  - Self-doping processes between planes and chains in the metal-to-superconductor
      transition of YBa2Cu3O6.9.
AB  - The interplay between the quasi 1-dimensional CuO-chains and the 2-dimensional
      CuO2 planes of YBa(2)Cu(3)O(6+x) (YBCO) has been in focus for a long time.
      Although the CuO-chains are known to be important as charge reservoirs that
      enable superconductivity for a range of oxygen doping levels in YBCO, the
      understanding of the dynamics of its temperature-driven metal-superconductor
      transition (MST) remains a challenge. We present a combined study using x-ray
      absorption spectroscopy and resonant inelastic x-ray scattering (RIXS) revealing
      how a reconstruction of the apical O(4)-derived interplanar orbitals during the
      MST of optimally doped YBCO leads to substantial hole-transfer from the chains
      into the planes, i.e. self-doping. Our ionic model calculations show that
      localized divalent charge-transfer configurations are expected to be abundant in
      the chains of YBCO. While these indeed appear in the RIXS spectra from YBCO in
      the normal, metallic, state, they are largely suppressed in the superconducting
      state and, instead, signatures of Cu trivalent charge-transfer configurations in
      the planes become enhanced. In the quest for understanding the fundamental
      mechanism for high-Tc-superconductivity (HTSC) in perovskite cuprate materials,
      the observation of such an interplanar self-doping process in YBCO opens a unique
      novel channel for studying the dynamics of HTSC.

PMID- 25388861
TI  - omega-Turn: a novel beta-turn mimic in globular proteins stabilized by main-chain
      to side-chain C-H...O interaction.
AB  - Mimicry of structural motifs is a common feature in proteins. The 10-membered
      hydrogen-bonded ring involving the main-chain C - O in a beta-turn can be formed
      using a side-chain carbonyl group leading to Asx-turn. We show that the N - H
      component of hydrogen bond can be replaced by a C(gamma) -H group in the side
      chain, culminating in a nonconventional C - H...O interaction. Because of its
      shape this beta-turn mimic is designated as omega-turn, which is found to occur ~
      three times per 100 residues. Three residues (i to i + 2) constitute the turn
      with the C - H...O interaction occurring between the terminal residues,
      constraining the torsion angles phii + 1, psii + 1, phii + 2 and chi'1(i + 2)
      (using the interacting C(gamma) atom). Based on these angles there are two types
      of omega-turns, each of which can be further divided into two groups. C(beta) 
      branched side-chains, and Met and Gln have high propensities to occur at i + 2;
      for the last two residues the carbonyl oxygen may participate in an additional
      interaction involving the S and amino group, respectively. With Cys occupying the
      i + 1 position, such turns are found in the metal-binding sites. N-linked
      glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2,
      the sequence can adopt the secondary structure of a omega-turn, which may be the
      recognition site for protein modification. Location between two beta-strands is
      the most common occurrence in protein tertiary structure, and being generally
      exposed omega-turn may constitute the antigenic determinant site. It is a stable
      scaffold and may be used in protein engineering and peptide design.

PMID- 25388862
TI  - High-flexion posterior-substituting versus cruciate-retaining prosthesis in total
      knee arthroplasty: functional outcome, range of motion and complication
      comparison.
AB  - PURPOSE: Currently, a high-flexion cruciate-retaining knee prosthesis has been
      designed to allow greater advantage after total knee arthroplasty (TKA). The
      present study was conducted to compare functional outcome, range of motion (ROM)
      as well as complications in subjects who underwent either a high-flexion cruciate
      retaining (HFCR, Group I) or a high-flexion posterior-substituting (HFPS, Group
      II) prosthesis TKA. METHODS: Thirty-four subjects which had TKA with HFCR
      prosthesis and thirty-three subjects which had TKA with HFPS prosthesis were
      enrolled in our study and were assessed preoperatively and at 24 months
      postoperatively. For functional outcome comparison, Hospital for Special Surgery
      Score (HSSS), Knee Society Score (KSS, including the Mean Knee Score and the Mean
      Function Score) as well as SF12 Score (including Mental Health Score and Physical
      Health Score) were measured. For ROM comparison, the arcs of maximal non-weight
      bearing passive flexion and weight-bearing flexion were detected, and the number
      of knees which allowed patients to kneel and sit cross-legged in comfort was
      determined. For complication comparison, wound necrosis/discharge, anterior knee
      pain, dislocation, radiolucent lines as well as osteolysis were investigated.
      RESULTS: At 24-month follow-up, no significant difference in functional outcome
      between the two groups was detected. The average maximal non-weight-bearing
      flexion was 136.2 degrees  for the knees in Group I and 135.1 degrees  for the
      knees in Group II (P > 0.05). The average weight-bearing flexion was 123.2
      degrees  for the knees in Group I and 129.8 degrees  for the knees in Group II (P
      > 0.05). No significant difference, with regard to the number of knees that
      allowed kneeling and sitting cross-legged, was detected. Comparisons of
      postoperative complications between the two groups did not yield a significant
      difference. CONCLUSIONS: Our study demonstrated no advantage of the high-flexion
      cruciate- retaining TKA over high-flexion posterior-substituting TKA with regard
      to functional outcome, range of motion as well as complications at short-term
      follow-up. However, longer follow-up is necessary to confirm whether these
      results are sustained.

PMID- 25388863
TI  - Distal femoral fractures in the elderly: biomechanical analysis of a polyaxial
      angle-stable locking plate versus a retrograde intramedullary nail in a human
      cadaveric bone model.
AB  - INTRODUCTION: Compromised bone quality and the need for early mobilization still
      lead to high rates of implant failure in geriatric patients with distal femoral
      fractures. With the newest generation of polyaxial locking plates and the proven
      retrograde femoral nails today two minimally invasive surgical procedures have
      been established. Indications for both procedures overlap. This study attempts to
      define the strength and failure mode of both surgical procedures. MATERIALS AND
      METHODS: A standardized fracture model was established to simulate an unstable
      AO/OTA 33-A3 fracture. Eight pairs of human cadaver femora (mean age 79 years,
      range 63-100 years) with compromised bone quality were used. Osteosyntheses with
      eight retrograde femoral nails and eight locking plates were randomly performed.
      A materials testing machine (Instron 5566) was used to perform cyclic stress
      tests according to a standardized loading protocol, up to a maximum load of 5,000
      N. RESULTS: All specimens survived loading of at least 2,500 N. Three nail and
      one plate construct survived a maximum load of 5,000 N. The mean compressive
      force leading to failure was 4,400 N (CI 4,122-4,678 N) for nail osteosynthesis
      and 4,429 N (CI 3,653-5,204 N) for plate osteosynthesis (p = 0.943). Proximal
      cutting out of the osteosynthesis was the most common reason for interruption in
      the nail and plate osteosyntheses. Significant differences between the retrograde
      femoral nail and plate osteosyntheses were seen under testing conditions for
      plastic deformation and stiffness of the constructs (p = 0.002 and p = 0.001,
      respectively). CONCLUSION: Based on our results, no statements regarding the
      superiority of either of the devices can be made. Even though the load to failure
      values for both osteosyntheses were much higher than the loads experienced during
      normal walking; however, because only axial loading was applied, it remains
      unclear whether both osteosyntheses meet the estimated requirements for
      postoperative full weight-bearing for an average heavy patient with a distal
      femoral fracture.

PMID- 25388864
TI  - Distal radius: anatomical morphometric gender characteristics. Do anatomical pre
      shaped plates pay attention on it?
AB  - INTRODUCTION: The purpose of the study was to investigate differences in the
      osseous structure anatomy of male and female distal radii. METHODS: Morphometric
      data were obtained of 49 distal human cadaveric radii. An imprint of the distal
      edge was attained using silicone mass and the palmar cortical angle (PCA) of the
      lateral and intermediate column, here declared as medial, according to the
      concept of Rikli and Rigazzoni. The lateral and medial length and five widths
      were digitally measured by three observers. In order to compare the measurements
      an unpaired t test was used. To prove the reliability of the measurements an
      intraclass correlation analyses was done. RESULTS: Overall mean medial PCA was
      148.25 degrees  (SD +/- 6.83) and mean lateral PCA 156.07 degrees  (SD +/- 7.00).
      In male specimens, the mean medial PCA was 147.38 degrees  (SD +/- 6.01) and mean
      lateral PCA was 153.6 degrees  (SD +/- 6.20) whereas in female specimens, the
      mean medial PCA was 149.41 degrees  (SD +/- 7.79) and the mean lateral PCA 159.37
      degrees  (SD +/- 6.78), with statistical significance for the female lateral PCA.
      No gender significant difference for the medial PCA and no significant side
      difference for the PCA's could be found. The ICC of the observers was r = 0.936
      and 0.976 for the medial and for lateral PCA 0.957-0.984. The palmar cortical
      length of the distal radius was significantly longer in male specimens. For all
      widths, larger values for male radii were measured, being statistically
      significant in all cases. CONCLUSION: Male dimensions concerning the wide were
      significantly larger when compared with females. Regarding the PCA at the medial
      and lateral column, we found significant difference for lateral PCA concerning
      the gender. Overall, study results demonstrated an angle of 148.25 degrees  +/-
      6.83 for the medial PCA and 156.07 degrees  +/- 7.00 for the lateral PCA.

PMID- 25388865
TI  - Age-related changes in neural gap detection thresholds in the rat auditory
      cortex.
AB  - The ability of the auditory system to resolve sound temporal information is
      crucial for the understanding of human speech and other species-specific
      communications. Gap detection threshold, i.e. the ability to detect the shortest
      duration of a silent interval in a sound, is commonly used to study the auditory
      temporal resolution. Behavioral studies in humans and rats have shown that normal
      developing infants have higher gap detection thresholds than adults; however, the
      underlying neural mechanism is not fully understood. In the present study, we
      determined and compared the neural gap detection thresholds in the primary
      auditory cortex of three age groups of rats: the juvenile group (postnatal day 20
      30), adult group I (8-10 weeks), and adult group II (28-30 weeks). We found age
      related changes in auditory temporal acuity in the auditory cortex, i.e. the
      proportion of cortical units with short neural gap detection thresholds (< 5 ms)
      was much lower in juvenile groups compared with that in both adult groups at a
      constant sound level, and no significant differences in neural gap detection
      thresholds were found between the two adult groups. In addition, units in the
      auditory cortex of each group generally showed better gap detection thresholds at
      higher sound levels than at lower sound levels, exhibiting a level-dependent
      temporal acuity. These results provided evidence for neural correlates of age
      related changes in behavioral gap detection ability during postnatal hearing
      development. 

PMID- 25388866
TI  - Sudden death of a horse with supraventricular tachycardia following oral
      administration of flecainide acetate.
AB  - OBJECTIVE: To describe a case of supraventricular tachycardia and sudden death in
      a horse following administration of flecainide acetate. CASE SUMMARY: An 8-year
      old Hanoverian warmblood gelding was treated for chronic, naturally occurring,
      supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine
      sulfate, and flecainide acetate. After oral administration of flecainide,
      polymorphic ventricular tachycardia (torsades de pointes) and ventricular
      fibrillation developed, leading to cardiovascular collapse and death. NEW OR
      UNIQUE INFORMATION PROVIDED: Atrial fibrillation is the most commonly diagnosed
      dysrhythmia associated with poor performance in horses, while atrial tachycardia
      is rarely documented. Here, we describe a case of sudden death in a horse with
      atrial tachycardia following the oral administration of flecainide acetate, after
      the lack of response to other antiarrhythmic drugs. Information provided in this
      case report is new and will make clinicians aware of the potential complications
      of flecainide alone or in combination with other drugs, in horses with cardiac
      dysrhythmias.

PMID- 25388867
TI  - In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence
      of abnormal myocardial laminar orientations and mobility in hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Cardiac diffusion tensor imaging (cDTI) measures the magnitudes and
      directions of intramyocardial water diffusion. Assuming the cross-myocyte
      components to be constrained by the laminar microstructures of myocardium, we
      hypothesized that cDTI at two cardiac phases might identify any abnormalities of
      laminar orientation and mobility in hypertrophic cardiomyopathy (HCM). METHODS:
      We performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11
      healthy controls and 11 patients with HCM, as well as late gadolinium enhancement
      (LGE) for detection of regional fibrosis. RESULTS: Voxel-wise analysis of
      diffusion tensors relative to left ventricular coordinates showed expected
      transmural changes of myocardial helix-angle, with no significant differences
      between phases or between HCM and control groups. In controls, the angle of the
      second eigenvector of diffusion (E2A) relative to the local wall tangent plane
      was larger in systole than diastole, in accord with previously reported changes
      of laminar orientation. HCM hearts showed higher than normal global E2A in
      systole (63.9 degrees  vs 56.4 degrees  controls, p=0.026) and markedly raised
      E2A in diastole (46.8 degrees  vs 24.0 degrees  controls, p<0.001). In
      hypertrophic regions, E2A retained a high, systole-like angulation even in
      diastole, independent of LGE, while regions of normal wall thickness did not (LGE
      present 57.8 degrees , p=0.0028, LGE absent 54.8 degrees , p=0.0022 vs normal
      thickness 38.1 degrees ). CONCLUSIONS: In healthy controls, the angles of cross
      myocyte components of diffusion were consistent with previously reported
      transmural orientations of laminar microstructures and their changes with
      contraction. In HCM, especially in hypertrophic regions, they were consistent
      with hypercontraction in systole and failure of relaxation in diastole. Further
      investigation of this finding is required as previously postulated effects of
      strain might be a confounding factor.

PMID- 25388868
TI  - Cerebral oximetry monitoring during sinus endoscopy.
AB  - OBJECTIVES/HYPOTHESIS: Deliberate hypotension, reverse Trendelenburg position,
      and hyperventilation are techniques utilized during functional endoscopic sinus
      surgery to attempt to reduce surgical bleeding. These methods may predispose
      patients to cerebral ischemia. Cerebral oximetry has not been investigated
      extensively within otolaryngologic surgery. Our study sought to address the
      question of whether cerebral oximetry is feasible in the FESS population and
      evaluate whether the data provided may be useful in the assessment of cerebral
      perfusion. STUDY DESIGN: Prospective, blinded, observational trial. METHODS: We
      designed a prospective, blinded, observational trial of patients undergoing
      functional endoscopic sinus surgery using cerebral oximetry monitoring. Collected
      data included mean arterial blood pressure (MAP), end-tidal carbon dioxide
      (EtCO2), cerebral saturation (SctO2), postanesthesia care unit (PACU) length of
      stay, and incidence of postoperative nausea and vomiting (PONV). RESULTS: Thirty
      one subjects were enrolled into the study. Univariate analyses showed cross
      correlation between concurrent EtCO2 values and SctO2 of 0.43 (95% CI: 0.27 to
      0.59) and between present EtCO2 and the SctO2 5 minutes later of 0.46 (95% CI:
      0.33 to 0.59). MAP was not significantly cross-correlated with SctO2. Patients
      who had an SctO2 below 60% at any time had a median (interquartile range [IQR])
      PACU length of stay of 167 (IQR, 95-386) minutes. Patients whose cerebral
      saturation did not fall below 60% at any time had a median PACU length of stay of
      103 (IQR, 76-155) minutes. This difference did not reach statistical significance
      (P = .257). The median (IQR) maximum decline in SctO2 for patients with PONV was
      11.2% (IQR, 8.2%-13.1%) and for patients without PONV was 7.1% (IQR, 5.1%-9.8%)
      (P = .126). CONCLUSIONS: Cerebral oximetry monitoring was feasible during
      functional endoscopic sinus surgery. This study demonstrated a cross-correlation
      between EtCO2 and SctO2, but not MAP and SctO2. A longer PACU length of stay and
      higher rate of PONV were seen but did not reach statistical significance.

PMID- 25388869
TI  - Hearing the voices of young people who self-harm: implications for service
      providers.
AB  - The incidence of adolescent self-harm and suicidal behaviour has increased
      globally, with many adolescents repeating the behaviour. While studies indicate
      that large numbers of adolescents who self-harm do not seek professional help,
      research focusing on barriers to help seeking from an adolescent perspective is
      limited. Locally, a rise in reported and unreported rates of self-harm and a
      number of suspected child suicides prompted the commissioning of a research
      project to ascertain young people's experiences of help and support for self-harm
      and how their future needs could be best met. Qualitative research, adopting an
      interpretive phenomenological analysis, was used to elicit narratives of
      adolescents engaging in self-harm. Data were collected via 1:1 interviews with
      seven participants and analysed in two stages: an analysis of each individual
      narrative, and thematic analysis across the group. Three themes were identified:
      (i) cutting out the stress; (ii) stepping onto the path of help; and (iii)
      cutting to the chase. In conclusion, mental health nurses have a vital role in
      providing knowledge and support to those likely to have initial contact with this
      vulnerable group and to the wider population, ensuring we more effectively
      address the increasing use of this risky behaviour among young people. 

PMID- 25388870
TI  - FID navigator-based MR thermometry method to monitor small temperature changes in
      the brain of ventilated animals.
AB  - An MR thermometry method is proposed for measuring in vivo small temperature
      changes engendered by external RF heat sources. The method relies on reproducible
      and stable respiration and therefore currently applies to ventilated animals
      whose breathing is carefully controlled. It first consists in characterizing the
      stability of the main magnetic field as well as the variations induced by
      breathing during a first monitoring stage. Second, RF heating is applied while
      the phase and thus temperature evolutions are continuously measured, the
      corrections due to breathing and field drift being made thanks to the data
      accumulated during the first period. The RF heat source is finally stopped and
      the temperature rise likewise is continuously monitored during a third and last
      stage to observe the animal cooling down and to validate the assumptions made for
      correcting for the main field variation and the physiological noise. Experiments
      were performed with a clinical 7 T scanner on an anesthetized baboon and with a
      dedicated RF heating setup. Analysis of the data reveals a precision around 0.1
      degrees C, which allows us to reliably measure sub-degree temperature rises in
      the muscle and in the brain of the animal.

PMID- 25388871
TI  - Quantitative ultrasound of denervated hand muscles.
AB  - INTRODUCTION: Presentations to the neuromuscular clinic commonly involve hand
      muscle denervation, but few studies have evaluated hand muscle ultrasound.
      METHODS: Ultrasound studies of abductor pollicis brevis, first dorsal
      interosseous, and abductor digit minimi were prospectively performed in a cohort
      of 34 patients (77 muscles) with electromyography (EMG)-confirmed denervation,
      compared with 58 healthy control subjects. RESULTS: In control subjects, muscle
      thickness was highly reproducible [intraclass correlation coefficient (ICC) =
      0.88-0.98], and echogenicity was moderately reproducible (ICC = 0.542-0.686).
      Age, gender, and body mass index influenced muscle thickness and echogenicity.
      Ultrasound changes in denervated muscles correlated with the severity of EMG
      abnormalities. A z-score cutoff of 0 identified denervated muscles with a
      sensitivity of 100% and 89% for echogenicity and muscle thickness, respectively.
      CONCLUSIONS: Hand muscle ultrasound provides a noninvasive method to quantify
      muscle denervation and may be useful as a screening tool before EMG studies.

PMID- 25388872
TI  - Synthesis and investigation of cobalt chalcogenide clusters with thienyl
      phosphine ligands as new acceptor materials for P3HT.
AB  - Cobalt selenide clusters with 2-bromo-5-diethylphosphinothiophene (1) and 2-bromo
      5-diphenylphosphinothiophene (2) ligands are described. The phosphine ligands are
      obtained via lithium halogen exchange of 2,5-dibromothiophene followed by
      addition of chlorodiethylphosphine and chlorodiphenylphosphine, respectively. The
      prepared phosphine ligands are then sequentially reacted with elemental selenium
      followed by dicobalt octacarbonyl to yield Co6Se8(P(Et)2(C4H2SBr))6 (3) or
      Co6Se8(P(Ph)2(C4H2SBr))6 (4), respectively. The two new cobalt selenide clusters
      were characterized by UV-visible spectroscopy, Fourier-transform infrared
      spectroscopy, cyclic voltammetry, powder X-ray diffraction, and elemental
      analysis. Emission spectra were recorded for the addition of, Co6Se8(PEt3)6 (5),
      3, and 4 to a 0.004 wt% solution of poly-3-hexyl thiophene (P3HT) in toluene to
      investigate the charge transport of the system. The quenching of the polymers'
      emission follows first-order like decay for each cluster. Clusters 3 and 4 are
      approximately twice as efficient at quenching the emission than cluster 5 with 4
      being slightly more efficient than 3. Simple mixtures of 3, 4 or 5 and P3HT were
      spun cast from toluene into thin films and atomic force microscopy displayed
      relatively uniform dispersion of 3 and network-like formation of 4 in contrast to
      the phase separation of 5 in the polymer films.

PMID- 25388873
TI  - Comparative cytogenetic analysis of marine needlefishes (Beloniformes) from
      southern Brazil.
AB  - Cytogenetic studies have assisted in the taxonomic classification of organisms,
      especially those involving species with highly similar morphologic
      characteristics, or so-called cryptic species. Strongylura marina and Strongylura
      timucu collected from Paranagua Bay, Parana Coast in Southern Brazil are
      considered cryptic species, and the identification of interspecific variations
      based on the number and/or morphology of its chromosomes may serve as
      differentiating cytotaxonomic markers. Chromosomes of the two species were
      subjected to different banding and staining methods (C-, Ag-, and DAPI-CMA3), as
      well as chromosomal mapping of major rDNA (45S), revealed with an 18S probe by
      fluorescence in situ hybridization (FISH). The pattern of distribution of
      constitutive heterochromatin showed distinct features involving the
      pericentromeric and telomeric bands in both species. In S. marina, chromosome 1
      represents the main species-specific marker, appearing almost entirely
      heterochromatic. In both species, the 45S rDNA is located at terminal region of
      the short arm of the chromosome 6, as detected by silver nitrate staining and
      FISH. Despite the apparent conserved diploid number of 48 chromosomes, data on
      the karyotype microstructure characterize the cytogenetic profile of the genus
      and may allow the establishment of cytotaxonomic and evolutionary inferences for
      these fishes. 

PMID- 25388874
TI  - Modeling the effect of nano-sized polymer particles on the properties of lipid
      membranes.
AB  - The interaction between polymers and biological membranes has recently gained
      significant interest in several research areas. On the biomedical side,
      dendrimers, linear polyelectrolytes, and neutral copolymers find application as
      drug and gene delivery agents, as biocidal agents, and as platforms for
      biological sensors. On the environmental side, plastic debris is often disposed
      of in the oceans and gets degraded into small particles; therefore concern is
      raising about the interaction of small plastic particles with living organisms.
      From both perspectives, it is crucial to understand the processes driving the
      interaction between polymers and cell membranes. In recent times progress in
      computer technology and simulation methods has allowed computational predictions
      on the molecular mechanism of interaction between polymeric materials and lipid
      membranes. Here we review the computational studies on the interaction between
      lipid membranes and different classes of polymers: dendrimers, linear charged
      polymers, polyethylene glycol (PEG) and its derivatives, polystyrene, and some
      generic models of polymer chains. We conclude by discussing some of the technical
      challenges in this area and future developments. 

PMID- 25388875
TI  - Reduced microsatellite heterozygosity does not affect natal dispersal in three
      contrasting roe deer populations.
AB  - Although theoretical studies have predicted a link between individual multilocus
      heterozygosity and dispersal, few empirical studies have investigated the effect
      of individual heterozygosity on dispersal propensity or distance. We investigated
      this link using measures of heterozygosity at 12 putatively neutral
      microsatellite markers and natal dispersal behaviour in three contrasting
      populations of European roe deer (Capreolus capreolus), a species displaying pre
      saturation condition-dependent natal dispersal. We found no effect of individual
      heterozygosity on either dispersal propensity or dispersal distance. Average
      heterozygosity was similar across the three studied populations, but dispersal
      propensity and distance differed markedly among them. In Aurignac, dispersal
      propensity and distance were positively related to individual body mass, whereas
      there was no detectable effect of body mass on dispersal behaviour in Chize and
      Trois Fontaines. We suggest that we should expect both dispersal propensity and
      distance to be greater when heterozygosity is lower only in those species where
      dispersal behaviour is driven by density-dependent competition for resources. 

PMID- 25388876
TI  - Competitive interactions between established grasses and woody plant seedlings
      under elevated CO2 levels are mediated by soil water availability.
AB  - The expansion of woody plants into grasslands has been observed worldwide and is
      likely to have widespread ecological consequences. One proposal is that woody
      plant expansion into grasslands is driven in part by the rise in atmospheric CO2
      concentrations. We have examined the effect of CO2 concentration on the
      competitive interactions between established C4 grasses and woody plant seedlings
      in a model grassland system. Woody plant seedlings were grown in mesocosms
      together with established C4 grasses in three competition treatments (root
      competition, shoot competition and root + shoot competition) under ambient and
      elevated CO2 levels. We found that the growth of the woody plant seedlings was
      suppressed by competition from grasses, with root and shoot competition having
      similar competitive effects on growth. In contrast to expectations, woody plant
      seedling growth was reduced at elevated CO2 levels compared to that at the
      ambient CO2 level across all competition treatments, with the most plausible
      explanation being reduced light and soil water availability in the elevated CO2
      mesocosms. Reduced light and soil water availability in the elevated CO2
      mesocosms was associated with an increased leaf area index of the grasses which
      offset the reductions in stomatal conductance and increased rainfall
      interception. The woody plant seedlings also had reduced 'escapability' (stem
      biomass and stem height) under elevated compared to ambient CO2 levels. Our
      results suggest that the expansion of woody plants into grasslands in the future
      will likely be context-dependent, with the establishment success of woody plant
      seedlings being strongly coupled to the CO2 response of competing grasses and to
      soil water availability. 

PMID- 25388878
TI  - The transmembrane protein FgSho1 regulates fungal development and pathogenicity
      via the MAPK module Ste50-Ste11-Ste7 in Fusarium graminearum.
AB  - The mitogen-activated protein kinase (MAPK) signaling pathways have been
      characterized in Fusarium graminearum. Currently, the upstream sensors of these
      pathways are unknown. Biological functions of a transmembrane protein FgSho1 were
      investigated using a target gene deletion strategy. The relationship between
      FgSho1 and the MAPK cassette FgSte50-Ste11-Ste7 was analyzed in depth. The
      transmembrane protein FgSho1 is required for conidiation, full virulence, and
      deoxynivalenol (DON) biosynthesis in F. graminearum. Furthermore, FgSho1 and
      FgSln1 have an additive effect on virulence of F. graminearum. The yeast two
      hybrid, coimmunoprecipitation, colocalization and affinity capture-mass
      spectrometry analyses strongly indicated that FgSho1 physically interacts with
      the MAPK module FgSte50-Ste11-Ste7. Similar to the FgSho1 mutant, the mutants of
      FgSte50, FgSte11, and FgSte7 were defective in conidiation, pathogenicity, and
      DON biosynthesis. In addition, FgSho1 plays a minor role in the response to
      osmotic stress but it is involved in the cell wall integrity pathway, which is
      independent of the module FgSte50-Ste11-Ste7 in F. graminearum. Collectively,
      results of this study strongly indicate that FgSho1 regulates fungal development
      and pathogenicity via the MAPK module FgSte50-Ste11-Ste7 in F. graminearum, which
      is different from what is known in the budding yeast Saccharomyces cerevisiae. 

PMID- 25388879
TI  - A method for automatic segmentation of nuclei in phase-contrast images based on
      intensity, convexity and texture.
AB  - This paper presents a method for automatic segmentation of nuclei in phase
      contrast images using the intensity, convexity and texture of the nuclei. The
      proposed method consists of three main stages: preprocessing, h-maxima
      transformation-based marker controlled watershed segmentation ( h-TMC), and
      texture analysis. In the preprocessing stage, a top-hat filter is used to
      increase the contrast and suppress the non-uniform illumination, shading, and
      other imaging artifacts in the input image. The nuclei segmentation stage
      consists of a distance transformation, h-maxima transformation and watershed
      segmentation. These transformations utilize the intensity information and the
      convexity property of the nucleus for the purpose of detecting a single marker in
      every nucleus; these markers are then used in the h-TMC watershed algorithm to
      obtain segments of the nuclei. However, dust particles, imaging artifacts, or
      prolonged cell cytoplasm may falsely be segmented as nuclei at this stage, and
      thus may lead to an inaccurate analysis of the cell image. In order to identify
      and remove these non-nuclei segments, in the third stage a texture analysis is
      performed, that uses six of the Haralick measures along with the AdaBoost
      algorithm. The novelty of the proposed method is that it introduces a systematic
      framework that utilizes intensity, convexity, and texture information to achieve
      a high accuracy for automatic segmentation of nuclei in the phase-contrast
      images. Extensive experiments are performed demonstrating the superior
      performance ( precision = 0.948; recall = 0.924; F1-measure = 0.936; validation
      based on  ~ 4850 manually-labeled nuclei) of the proposed method. 

PMID- 25388877
TI  - Gastrointestinal helminths may affect host susceptibility to anthrax through
      seasonal immune trade-offs.
AB  - BACKGROUND: Most vertebrates experience coinfections, and many pathogen-pathogen
      interactions occur indirectly through the host immune system. These interactions
      are particularly strong in mixed micro-macroparasite infections because of
      immunomodulatory effects of helminth parasites. While these trade-offs have been
      examined extensively in laboratory animals, few studies have examined them in
      natural systems. Additionally, many wildlife pathogens fluctuate seasonally, at
      least partly due to seasonal host immune changes. We therefore examined
      seasonality of immune resource allocation, pathogen abundance and exposure, and
      interactions between infections and immunity in plains zebra (Equus quagga) in
      Etosha National Park (ENP), Namibia, a system with strongly seasonal patterns of
      gastrointestinal (GI) helminth infection intensity and concurrent anthrax
      outbreaks. Both pathogens are environmentally transmitted, and helminth
      seasonality is driven by environmental pressures on free living life stages. The
      reasons behind anthrax seasonality are currently not understood, though anthrax
      is less likely directly driven by environmental factors. RESULTS: We measured a
      complex, interacting set of variables and found evidence that GI helminth
      infection intensities, eosinophil counts, IgE and IgGb antibody titers, and
      possibly IL-4 cytokine signaling were increased in wetter seasons, and that
      ectoparasite infestations and possibly IFN-gamma cytokine signaling were
      increased in drier seasons. Monocyte counts and anti-anthrax antibody titers were
      negatively associated with wet season eosinophilia, and monocytes were negatively
      correlated with IgGb and IgE titers. Taken together, this supports the hypothesis
      that ENP wet seasons are characterized by immune resource allocation toward Th-2
      type responses, while Th1-type immunity may prevail in drier seasons, and that
      hosts may experience Th1-Th2 trade-offs. We found evidence that this Th2-type
      resource allocation is likely driven by GI parasite infections, and that these
      trade-offs may render hosts less capable of concurrently mounting effective Th1
      type immune responses against anthrax. CONCLUSIONS: This study is one of the
      first to examine laboratory-demonstrated Th1-Th2 trade-offs in a natural system.
      It provides evidence that seasonally bound pathogens may affect, through
      immunology, transmission dynamics of pathogens that might otherwise not be
      seasonally distributed. It suggests that, by manipulating the internal host
      ecosystem, GI parasites may influence the external ecosystem by affecting the
      dynamics of another environmentally transmitted pathogen.

PMID- 25388880
TI  - A robust method for pulse peak determination in a digital volume pulse waveform
      with a wandering baseline.
AB  - This paper presents a robust method for pulse peak determination in a digital
      volume pulse (DVP) waveform with a wandering baseline. A proposed new method uses
      a modified morphological filter (MMF) to eliminate a wandering baseline signal of
      the DVP signal with minimum distortion and a slope sum function (SSF) with an
      adaptive thresholding scheme to detect pulse peaks from the baseline-removed DVP
      signal. Further in order to cope with over-detected and missed pulse peaks,
      knowledge based rules are applied as a postprocessor. The algorithm automatically
      adjusts detection parameters periodically to adapt to varying beat morphologies
      and fluctuations. Compared with conventional methods (highpass filtering, linear
      interpolation, cubic spline interpolation, and wavelet adaptive filtering), our
      method performs better in terms of the signal-to-error ratio, the computational
      burden (0.125 seconds for one minute of DVP signal analysis with the Intel Core 2
      Quad processor @ 2.40 GHz PC), the true detection rate (97.32% with an acceptance
      level of 4 ms ) as well as the normalized error rate (0.18%). In addition, the
      proposed method can detect true positions of pulse peaks more accurately and
      becomes very useful for pulse transit time (PTT) and pulse rate variability (PRV)
      analyses. 

PMID- 25388881
TI  - A 10.5 cm ultrasound link for deep implanted medical devices.
AB  - A study on ultrasound link for wireless energy transmission dedicated to deeply
      implanted medical devices is presented. The selection of the frequency to avoid
      biological side effects (e.g., cavitations), the choice of the power amplifier to
      drive the external transducers and the design of the rectifier to maximize the
      energy extraction from the implanted transducer are described in details. The
      link efficiency is characterized in water using a phantom material for a
      transmitter-receiver distance of 105 mm, transducers active area of 30 mm * 96 mm
      and 5 mm * 10 mm, respectively, and a system efficiency of 1.6% is measured. 

PMID- 25388882
TI  - Using an interactive water bottle to target fluid adherence in pediatric kidney
      transplant recipients: a pilot study.
AB  - Hydration is important post-renal transplant to maintain adequate renal perfusion
      and graft function. Adherence to fluid recommendations is challenging given
      barriers to staying hydrated. There are no studies of adherence to fluid intake
      recommendations following pediatric renal transplant. Through this pilot study,
      we sought to determine whether the use of a commercially available interactive
      water bottle would lead to better adherence to recommended fluid intake and
      improved kidney functioning post-transplant relative to standard of care.
      Participants included 32 youth ages 7-19 >=1 month post-kidney transplant
      randomized to the intervention (HydraCoach((r)) water bottle) or standard
      education control group. Laboratory records were reviewed for serum chemistries
      (Na, BUN, creatinine) at baseline and one-month follow-up, and participants
      recorded daily fluid intake for 28 days. Those in the intervention group were
      significantly more likely to meet or exceed their fluid target, but this did not
      translate into better kidney functioning. Participants in the intervention group
      largely reported satisfaction with the water bottle and were likely to continue
      its use. While an interactive water bottle providing real-time feedback may be a
      promising intervention to help pediatric kidney transplant patients meet fluid
      goals, it did not appear to impact kidney function. 

PMID- 25388883
TI  - Development and validation of the Surgical Outcome Risk Tool (SORT).
AB  - BACKGROUND: Existing risk stratification tools have limitations and clinical
      experience suggests they are not used routinely. The aim of this study was to
      develop and validate a preoperative risk stratification tool to predict 30-day
      mortality after non-cardiac surgery in adults by analysis of data from the
      observational National Confidential Enquiry into Patient Outcome and Death
      (NCEPOD) Knowing the Risk study. METHODS: The data set was split into derivation
      and validation cohorts. Logistic regression was used to construct a model in the
      derivation cohort to create the Surgical Outcome Risk Tool (SORT), which was
      tested in the validation cohort. RESULTS: Prospective data for 19 097 cases in
      326 hospitals were obtained from the NCEPOD study. Following exclusion of 2309,
      details of 16 788 patients were analysed (derivation cohort 11 219, validation
      cohort 5569). A model of 45 risk factors was refined on repeated regression
      analyses to develop a model comprising six variables: American Society of
      Anesthesiologists Physical Status (ASA-PS) grade, urgency of surgery (expedited,
      urgent, immediate), high-risk surgical specialty (gastrointestinal, thoracic,
      vascular), surgical severity (from minor to complex major), cancer and age 65
      years or over. In the validation cohort, the SORT was well calibrated and
      demonstrated better discrimination than the ASA-PS and Surgical Risk Scale; areas
      under the receiver operating characteristic (ROC) curve were 0.91 (95 per cent
      c.i. 0.88 to 0.94), 0.87 (0.84 to 0.91) and 0.88 (0.84 to 0.92) respectively (P <
      0.001). CONCLUSION: The SORT allows rapid and simple data entry of six
      preoperative variables, and provides a percentage mortality risk for individuals
      undergoing surgery.

PMID- 25388885
TI  - Weight loss prior to bariatric surgery: an updated review of the literature.
AB  - BACKGROUND AND AIMS: Prior to bariatric surgery, a preoperative weight-reducing
      regimen is usually adhered to in most centers. The clinical effects of such a
      regimen are yet to be determined. MATERIAL AND METHODS: We reviewed the current
      literature by searching in PubMed for publications reporting clinical effects
      resulting from a preoperative weight loss regimen prior to bariatric surgery
      published from January 1, 1995 to April 30, 2014. RESULTS: In total, we
      identified 23 original publications and 2 review articles which met all inclusion
      criteria. These were included and fully analyzed with regard to effects of
      preoperative weight loss. In general, for parameters such as operating time and
      intraoperative complications including blood loss and recovery, inconsistent data
      were reported. Most studies included low number of patients and with heterogenic
      designs, and the results could not form the base for recommendations. However,
      for outcomes such as postoperative complications and weight development over
      time, data from large-scale studies and randomized controlled trials suggest
      beneficial effects following adherence to weight loss prior to bariatric surgery.
      CONCLUSION: Although a large amount of data in the current literature on the
      effects of weight loss prior to bariatric surgery are inconsistent for many
      outcome parameters, recently published results regarding effects on postoperative
      complications and weight development over time strongly suggest that such a
      regimen should be recommended. Whether a certain degree of weight loss should be
      mandatory before being accepted for bariatric surgery is, however, still
      controversial.

PMID- 25388886
TI  - Bariatric surgery in adolescents: what do we know so far?
AB  - INTRODUCTION: Obesity represents a vast and rapidly increasing global burden.
      Bariatric surgery is the only intervention achieving sustained weight loss, among
      its wide-ranging benefits. METHODS: In this article, we describe the growing
      challenges presented by adolescents with severe obesity and review the literature
      on surgical and other treatment options. RESULTS: Outcomes in terms of weight
      loss, metabolic and quality of life improvement, reversal of obstructive sleep
      apnea, insulin resistance, type II diabetes mellitus, hypertension, and
      dyslipidemia appear comparable to those seen in adults. However, long-term data
      on safety and sustainability are lacking. There is a growing acceptance of the
      need for surgery as a treatment for the morbidly obese adolescent population, and
      the number of studies reporting outcomes after adolescent bariatric surgery is
      increasing. CONCLUSION: Accumulating evidence suggests that the benefits seen in
      adult bariatric surgery can be reproduced in adolescents. Thus, adolescent
      bariatric surgery appears to be safe and effective in achieving benefits desired
      in terms of weight control and improvements in metabolic health and quality of
      life. However, particular care must be taken when treating a young population,
      and long-term outcomes are awaited to properly define indications and
      limitations.

PMID- 25388887
TI  - Polyoxometalates as inorganic chiral ligands for the synthesis of chiral
      nanoparticles.
AB  - Inherent chiral polyoxometalates, while acting as stabilizers, are developed into
      inorganic chiral ligands for the synthesis of chiral metal nanoparticles. The
      generated optical activity and stabilization of the nanoparticles are found to
      source from the strong interaction with polyoxometalate clusters. 

PMID- 25388888
TI  - Gold nanoaggregates for probing single-living cell based on surface-enhanced
      Raman spectroscopy.
AB  - Gold nanoparticles are delivered into living cells by transient electroporation
      method to obtain intracellular surface-enhanced Raman spectroscopy (SERS). The
      subcellular localization of gold nanoparticles is characterized by transmission
      electron microscopy, and the forming large gold nanoaggregates are mostly found
      in the cytoplasm. The SERS detection of cells indicates that this kind of gold
      nanostructures induces a high signal enhancement of cellular chemical
      compositions, in addition to less cellular toxicity than that of silver
      nanoparticles. These results demonstrate that rapid incorporation of gold
      nanoparticles by electroporation into cells has great potential applications in
      the studies of cell biology and biomedicine.

PMID- 25388890
TI  - The LQSP tetrapeptide is a new highly efficient substrate of microbial
      transglutaminase for the site-specific derivatization of peptides and proteins.
AB  - Transglutaminases catalyze transglutamination reactions on glutamines.
      Transglutaminases are largely exploited for modifying proteins in pharmaceutical,
      food, and other biotechnological applications. A library of synthetic peptides
      has been designed, prepared, and screened to identify new peptide substrates. The
      new substrates are then used in TGAse-mediated conjugation reactions to engraft
      synthons onto biomolecules. These peptide substrates confer the bioactive
      peptides and proteins with new properties. We have identified an optimized
      substrate named LQSP, which is recognized and processed by microbial TGAse with a
      strikingly higher efficiency compared to the well-known TQGA sequence. The new
      substrate has been used to selectively modify prototypical bioactive peptides and
      proteins with fluoresceine or recognition motifs. We show that, where a reactive
      lysine is available, proteins and peptides of relevant therapeutic interest, can
      be selectively and smoothly modified in order to incorporate new functions such
      as fluorescent labels, recognition units, or reactive groups. 

PMID- 25388889
TI  - Pre- and posttreatment with edaravone protects CA1 hippocampus and enhances
      neurogenesis in the subgranular zone of dentate gyrus after transient global
      cerebral ischemia in rats.
AB  - Edaravone is clinically used for treatment of patients with acute cerebral
      infarction. However, the effect of double application of edaravone on
      neurogenesis in the hippocampus following ischemia remains unknown. In the
      present study, we explored whether pre- and posttreatment of edaravone had any
      effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of
      hippocampus in a rat model of transient global cerebral ischemia and elucidated
      the potential mechanism of its effects. Male Sprague-Dawley rats were divided
      into three groups: sham-operated (n = 15), control (n = 15), and edaravone
      treated (n = 15) groups. Newly generated cells were labeled by 5-bromo-2
      deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to
      detect cell apoptosis. Reactive oxygen species (ROS) were detected by 2,7
      dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor
      1alpha (HIF-1alpha) and cleaved caspase-3 proteins were quantified by western
      blot analysis. Treatment with edaravone significantly increased the number of
      NSPCs and newly generated neurons in the subgranular zone (p < .05). Treatment
      with edaravone also decreased apoptosis of NSPCs (p < .01). Furthermore,
      treatment with edaravone significantly decreased ROS generation and inhibited HIF
      1alpha and cleaved caspase-3 protein expressions. These findings indicate that
      pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs
      from apoptosis in the hippocampus, which is probably mediated by decreasing ROS
      generation and inhibiting protein expressions of HIF-1alpha and cleaved caspase-3
      after cerebral ischemia.

PMID- 25388891
TI  - Blue rubber bleb naevus syndrome: a rare cause of iron deficiency anaemia.
AB  - We report a case in an adolescent male patient with a history of chronic fatigue,
      headache and unexplained iron deficiency anaemia since 2007. Numerous bluish
      black lesions were found over his body surface. A surgical scar from a previous
      lumpectomy with a small lump were noted at the left submandibular region and
      another smaller lesion on the left lobe of the thyroid was also palpated. His
      most recent blood indices displayed the presence of moderately severe iron
      deficiency anaemia. Endoscopic evaluation exhibited multiple vascular lesions
      throughout the gastrointestinal tract. MRI of the brain revealed an irregular
      intracranial vascular lesion at the cerebellopontine angle. Further work-up with
      abdominal CT demonstrated the absence of similar lesions in the extraintestinal
      abdominal organs. Putting these together with histological findings, the
      diagnosis of blue rubber bleb naevus syndrome was confirmed. The patient was
      treated conservatively at this point and future management planning was discussed
      with him. 

PMID- 25388892
TI  - Aortoduodenal syndrome in a patient receiving maintenance haemodialysis.
AB  - An 83-year-old man receiving maintenance haemodialysis presented with abdominal
      pain, fever and emesis. He was initially diagnosed with acute cholecystitis. His
      pain and fever improved with fasting and antibiotics, but he continued to suffer
      from anorexia and emesis. Enhanced abdominal CT scan showed evidence of superior
      mesenteric artery (SMA) syndrome versus obstruction of the third part of the
      duodenum caused by abdominal aortic aneurysm (AAA), the so-called aortoduodenal
      syndrome. An upper gastrointestinal contrast study revealed duodenal dilation and
      blockage of the third part of the duodenum. The AAA continued to enlarge over the
      subsequent 3 months and the intra-abdominal visceral fat volume decreased over 1
      month. The aortomesentric angle and distance remained within normal ranges.
      Ultimately, the patient was diagnosed with aortoduodenal syndrome. In the present
      case, a duodenal obstruction was caused by the combination of an enlarged AAA and
      reduced intra-abdominal visceral fat in a patient receiving maintenance
      haemodialysis.

PMID- 25388893
TI  - Synchronous anal squamous carcinoma and sigmoid adenocarcinoma.

PMID- 25388894
TI  - Beating heart myocardial revascularisation of a sudden cardiac death survivor
      with spontaneous coronary artery dissection: pitfalls from diagnosis to surgery.
AB  - Spontaneous coronary artery dissection is a rare clinical condition with a wide
      range of clinical presentations ranging from asymptomatic cases to life
      threatening ventricular arrhythmias and sudden cardiac death. The exact
      pathophysiological mechanism has not been fully established yet. We would like to
      present a survivor of sudden cardiac death presenting with ventricular
      fibrillation due to spontaneous coronary artery dissection. The prompt
      evaluation, medical management, surgical myocardial revascularisation and value
      of off-pump coronary artery bypass surgery are discussed. 

PMID- 25388895
TI  - Intra-abdominal abscess formation from the ingestion of a fish bone.

PMID- 25388896
TI  - It is all in the sputum: a case of non-resolving pneumonia.

PMID- 25388898
TI  - Importance of excitonic effect in charge separation at quantum-dot/organic
      interface: first-principles many-body calculations.
AB  - The staggered alignment of quasiparticle energy levels is widely regarded to be
      the key criterion necessary for electron-hole charge separation to occur at
      heterogeneous material interfaces. However, staggered energy levels at nanoscale
      interfaces, such as those between organic molecules and inorganic quantum dots,
      do not necessarily imply charge separation across the interface because the
      excitonic effect is often significant. Using quantum Monte Carlo calculations, we
      perform a detailed study of the role of the excitonic effects on charge
      separation across a representative set of interfaces between organic molecules
      and quantum dots. We find that the exciton binding energy of charge transfer
      excitons is significantly larger than would be estimated from a simple Coulombic
      analysis and, at these nanoscale interfaces, can be as significant as that of
      Frenkel excitons. This implies that charge transfer excitons can act as trap
      states and facilitate electron-hole recombination instead of charge separation.
      We conclude that in general, for nanoscale interfaces, high-fidelity quantum many
      body calculations are essential for an accurate evaluation of the detailed
      energetic balance between localized and delocalized excitons and, thus, are
      crucial for the predictive treatment of interfacial charge separation processes. 

PMID- 25388899
TI  - Acral lympho-histiocytic dermatitis in X-linked agammaglobulinemia: a case report
      showing clonal CD8(+) T cells with indolent clinical behaviour.

PMID- 25388900
TI  - Well-differentiated syringomatous carcinoma with solid carcinoma-like features.

PMID- 25388902
TI  - Laboratory investigation of anaphylaxis: not as easy as it seems.

PMID- 25388901
TI  - A proposed scheme for classifying pediatric rib head fractures using case
      examples.
AB  - Pediatric rib head fractures are typically described as "posterior" or
      "costovertebral," terms lacking specificity. To resolve this issue, a scheme was
      developed to describe the location of rib head fractures observed in a pediatric
      forensic population. The scheme uses three anatomical landmarks, terminus (tip),
      tubercle, and costovertebral articular surface to divide the rib head into two
      subregions, costovertebral and costotransverse. Examples of five cases of infants
      with rib head fractures are presented using this scheme. Forty-eight rib head
      fractures were observed in these infants with the following frequencies: 56%
      (three infants) at the terminus; 21% (three infants) in the costovertebral
      subregion; 21% (one infant) at the costovertebral articular facet; and 2% (one
      infant) in the costotransverse subregion. Due to the small number of cases
      assessed, statistical analyses could not be performed; however, the data
      demonstrate the variation in distribution of pediatric rib head fractures. 

PMID- 25388903
TI  - A rare type of drowning with a latent period following surviving an episode of
      immersion.
AB  - Drowning is a leading cause of accidental death worldwide and its diagnosis is an
      important part of forensic investigation. It is generally acknowledged that
      hypoxia due to airway obstruction by fluid is the primary mechanism of death in
      drowning. Drowned individuals are usually found dead in the water or show severe
      clinical signs once out of the water. However, sudden death due to drowning after
      a short period of recovery following immersion/submersion has rarely been
      reported. A case of a 40-year-old man who died suddenly due to severe pulmonary
      edema about 40 min after he was recovered from an episode of immersion is
      reported. We suspected delayed lung injury due to water aspiration as the prime
      cause of death. This rare type of drowning should be well recognized by a
      clinician or forensic pathologist.

PMID- 25388904
TI  - [Paratesticular mesothelioma].
AB  - Paratesticular mesothelioma is a very rare entity of this aggressive malignancy.
      In 30-40 % of all cases an exposition to asbestos exists in the anamnesis. We
      report on a typical case of paratesticular mesothelioma in a roof slater and
      tiler who had had occupational contact with asbestos-containing materials over
      decades. The recommended diagnostics and therapy are discussed and the importance
      of the identification as an occupational disease is emphasized. 

PMID- 25388905
TI  - [Oncological healthcare research in urology - perspectives].
AB  - Healthcare research has become established as an interdisciplinary self-contained
      field of research. It has now arrived in oncology and also provides important
      knowledge on healthcare events and for analysis of healthcare quality in urology.
      Because healthcare research covers a broad range both methodologically and in
      content, it is not always easy to maintain an overview of the many concurrently
      occurring developments. This article describes three current developments, which
      will probably be come of great importance for oncological healthcare research in
      the coming years and will also play a role in urology. 

PMID- 25388906
TI  - Host candidate gene polymorphisms and associated clearance of P. falciparum
      amodiaquine and fansidar resistance mutants in children less than 5 years in
      Cameroon.
AB  - BACKGROUND: In this post-hoc analysis, we determined the influence of single
      nucleotide polymorphisms in host candidate immune genes on the outcome of drug
      resistant malaria in Cameroon. METHODS: Human DNA from 760 patients from a
      previous clinical trial was subjected to mass spectrometry-based single
      nucleotide polymorphism (SNP) genotyping. Allele frequencies of candidate immune
      genes were calculated for 62 SNPs on 17 human chromosomes for their possible
      involvement in clearance of drug-resistant parasites with the triple mutations of
      pfcrt76T, pfmdr86Y, and pfmdr1246Y (TY) and pfdhfr51I, pfdhfr59R, pfdhfr108N, and
      pfdhps437G (IRNG) which were determined by dotblot or PCR-restriction analysis.
      Differences in SNP frequencies and association analysis were carried out by
      comparing Chi-square odds ratios (ORs) and stratified by Mantel-Haenzel
      statistics. An adjusted P value (OR) <0.0008 was considered significant. RESULTS:
      Post-treatment drug failure rates were amodiaquine (36.4%);
      sulpadoxine/pyrimethamine-amodiaquine combination (15.4%); and
      sulphadoxine/pyrimethamine (18.1%). SNPs in IL22, IL-4R1, and CD36 appeared to
      have been associated with clearance of resistant parasites [p  =  0.017, OR (C
      allele):1.44, 95% CI (OR): 1.06-1.95]; [P  =  0.014, OR  =  1.31, 95% CI (OR):
      1.07-1.83]; [P  =  5.78*10(-5), OR  =  0.27, 95%CI (OR): 0.13-0.54],
      respectively, with high fever (>39 degrees C for 48 hours) [IL-22, P  =  0.01, OR
      =  1.5, 95% CI (OR): 1.8-2.1] and also in high frequency among the Fulani
      participants [P  =  0.006, OR  =  1.83, 95% CI (OR): 1.11-3.08)]. The CD36-1264
      null allele was completely absent in the northern population. CONCLUSION:
      Independent association of SNPs in IL22 and IL-4 with clearance of amodiaquine-
      and sulphadoxine/pyrimethamine-resistant parasites did not reach statistical
      significance, but may suggest that not all drug-resistant mutants are adversely
      affected by the same immune-mediated mechanisms of clearance.

PMID- 25388907
TI  - Insights into genotype-phenotype correlations from CREBBP point mutation
      screening in a cohort of 46 Rubinstein-Taybi syndrome patients.
AB  - The genetic basis of Rubinstein-Taybi syndrome (RSTS), a rare, sporadic,
      clinically heterogeneous disorder characterized by cognitive impairment and a
      wide spectrum of multiple congenital anomalies, is primarily due to private
      mutations in CREBBP (approximately 55% of cases) or EP300 (approximately 8% of
      cases). Herein, we report the clinical and the genetic data taken from a cohort
      of 46 RSTS patients, all carriers of CREBBP point mutations. Molecular analysis
      revealed 45 different gene alterations including 31 inactivating (21 frameshift
      and 10 nonsense), 10 missense and 4 splicing mutations. Bioinformatic tools and
      transcript analyses were used to predict the functional effects of missense and
      splicing alterations. Of the 45 mutations, 42 are unreported and 3 were described
      previously. Recurrent mutations maybe a key tool in addressing genotype-phenotype
      correlations in patients sharing the same defects (at the genomic or transcript
      level) and specific clinical signs, demonstrated here in two cases. The clinical
      data of our cohort evidenced frequent signs such as arched eyebrows, epicanthus,
      synophrys and/or frontal hypertrichosis and broad phalanges that, previously
      overlooked in RSTS diagnosis, now could be considered. Some suggested
      correlations between organ-specific anomalies and affected CREB-binding protein
      domains broaden the RSTS clinical spectrum and perhaps will enhance patient
      follow-up and clinical care. 

PMID- 25388908
TI  - Sitagliptin attenuates sympathetic innervation via modulating reactive oxygen
      species and interstitial adenosine in infarcted rat hearts.
AB  - We investigated whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor,
      attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression in
      post-infarcted normoglycemic rats, focusing on adenosine and reactive oxygen
      species production. DPP-4 bound adenosine deaminase has been shown to catalyse
      extracellular adenosine to inosine. DPP-4 inhibitors increased adenosine levels
      by inhibiting the complex formation. Normoglycemic male Wistar rats were
      subjected to coronary ligation and then randomized to either saline or
      sitagliptin in in vivo and ex vivo studies. Post-infarction was associated with
      increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine
      and dihydroethidium fluorescent staining. Measurement of myocardial
      norepinephrine levels revealed a significant elevation in vehicle-treated
      infarcted rats compared with sham. Compared with vehicle, infarcted rats treated
      with sitagliptin significantly increased interstitial adenosine levels and
      attenuated oxidative stress. Sympathetic hyperinnervation was blunted after
      administering sitagliptin, as assessed by immunofluorescent analysis and western
      blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the
      sitagliptin-treated infarcted rats were significantly lower than those in
      vehicle. Ex vivo studies showed a similar effect of erythro-9-(2-hydroxy-3-nonyl)
      adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated levels of
      superoxide and NGF. Furthermore, the beneficial effects of sitagliptin on
      superoxide anion production and NGF levels can be reversed by 8-cyclopentyl-1,3
      dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine.
      Sitagliptin protects ventricular arrhythmias by attenuating sympathetic
      innervation via adenosine A1 receptor and xanthine oxidase-dependent pathways,
      which converge through the attenuated formation of superoxide in the non-diabetic
      infarcted rats. 

PMID- 25388909
TI  - Indirect comparison between subcutaneous biologic agents in ankylosing
      spondylitis.
AB  - BACKGROUND AND OBJECTIVE: There are four efficacious subcutaneous anti-tumor
      necrosis factor alpha (TNF-alpha) agents used for the therapy of ankylosing
      spondilitis (AS), but apparently little or no differences in their effectiveness
      was proven. By this study, we aimed to compare Assessment in Ankylosing
      Spondylitis Response Criteria 20 response patterns (ASAS20) between subcutaneous
      approved biological agents in patients affected by ankylosing spondylitis by
      means of a mixed treatment comparison of different randomized controlled trials
      (RCTs) on the efficacy of biological therapies. METHODS: A search in scientific
      literature was performed to identify the most complete collection of RCTs
      available on the selected topic. Similarly designed double-blind, randomized,
      placebo-controlled trials investigating the efficacy of the subcutaneous and
      approved TNF-alpha inhibitors such as etanercept, certolizumab pegol, golimumab
      and adalimumab in the treatment of ankylosing spondylitis patients were
      identified. The endpoint of interest was ASAS20 response criterium at 12 weeks.
      Results were analysed simultaneously using Bayesian mixed treatment comparison
      techniques. Results were expressed as odds ratio (OR) of positive ASAS20 response
      and associated 95 % credible intervals (CrIs). The probability of being the best
      treatment was also reported. RESULTS: Only five RCTs matched the inclusion
      criteria for consequent data extraction and analysis. Mixed treatment comparison
      of data from such RCTs demonstrated that all subcutaneous anti-TNF-alpha agents
      are more effective in inducing an ASAS20 response than placebo. Data from 24
      weeks' follow-up were not taken into account as early escape granted in some of
      the studies made results at 24 weeks unmatchable. In our analysis, golimumab
      proved to be the drug that more probably represents the best choice for achieving
      ASAS20 response at 12 weeks, although no differences were observed when comparing
      directly every single subcutaneous anti-TNF-alpha agent against another.
      CONCLUSIONS: Even if the mixed treatment comparisons between adalimumab,
      golimumab, certolizumab pegol and etanercept did not show a statistically
      significant difference, this analysis, based on data from only five RCTs,
      suggests that golimumab, compared to placebo, may be the drug that provides the
      highest probability of achieving ASAS20 response in AS patients naive to biologic
      treatments at 12 weeks.

PMID- 25388910
TI  - Comparative analysis of autistic traits and behavioral disorders in Prader-Willi
      syndrome and Asperger disorder.
AB  - Prader-Willi syndrome (PWS) is a neuro-genetic disorder caused by the
      absence/loss of expression of one or more paternally expressed genes on
      chromosome 15 (q11-13). In this study, a comparative analysis of intelligence
      level and autistic traits was conducted between children with PWS (n = 30; 18
      males, 12 females; age = 10.6 +/- 2.8 years) and those with Asperger disorder
      (AD; n = 31; 24 males, 7 females; age = 10.5 +/- 3.1 years). The children were
      compared by age group: lower elementary school age (6-8 years), upper elementary
      school age (9-12 years), and middle school age (13-15 years). As results, the
      intelligence levels of children with PWS were significantly lower than those with
      AD across all age groups. Autistic traits, assessed using the Pervasive
      Developmental Disorders Autism Society Japan Rating Scale (PARS), revealed that
      among elementary school age children, those with PWS had less prominent autistic
      traits than those with AD, however, among middle school age children, those with
      PWS and AD showed similar prominence. An analysis of the PARS subscale scores by
      age group showed that while the profiles of autistic traits for children with PWS
      differed from those of children with AD at elementary school age, the profiles
      showed no significant differences between the groups at middle school age. The
      findings suggest that autistic traits in PWS become gradually more prominent with
      increasing of age and that these autistic traits differ in their fundamental
      nature from those observed in AD.

PMID- 25388912
TI  - Colocalization of vitiligo and alopecia areata presenting as poliosis.
AB  - Vitiligo and alopecia areata are two cutaneous diseases believed to be primarily
      autoimmune in pathogenesis. While the coexistence of the two conditions in the
      same patient has been well-described, reports of the two disease processes
      occurring in the same location are rare. We report the case of a 10-year-old male
      with an unremarkable past medical history who presented with a single localized
      area of poliosis with depigmented underlying skin on the frontal scalp. The hair
      in the affected area was relatively decreased in density. A punch biopsy of the
      depigmented patch demonstrated features consistent with both vitiligo and
      alopecia areata. The decreased number of large hair follicles and a focal
      peribulbar lymphocytic infiltrate around an anagen follicle were suggestive of
      alopecia areata. A panel of melanocyte-specific stains revealed absent
      melanocytes in the epidermis, consistent with vitiligo. Loss of microphthalmia
      associated transcription factor-positive root sheath cells was seen, suggestive
      of loss of melanocyte stem cells. The combination of clinical and histopathologic
      findings supports the theory of a common pathogenesis of alopecia areata and
      vitiligo. 

PMID- 25388911
TI  - Gender specific association of a complement component 3 polymorphism with
      polypoidal choroidal vasculopathy.
AB  - Neovascular age-related macular degeneration (AMD) and polypoidal choroidal
      vasculopathy (PCV) are leading causes of irreversible blindness in developed
      countries. In this study, we investigated the associations of haplotype-tagging
      single nucleotide polymorphisms (SNPs) in the complement component 3 (C3) gene
      with both neovascular AMD and PCV, and potential epistatic effects on C3. Eight
      tagging SNPs in C3 were genotyped in 708 unrelated study subjects: 200
      neovascular AMD patients, 233 PCV patients and 275 controls. Among the eight C3
      SNPs, rs17030 was associated with PCV after adjusted for gender and SNP-gender
      interaction (P = 0.008, OR = 2.94; 95% CI: 1.32-6.52). Moreover, an interaction
      between rs17030 and gender was identified in PCV (P = 0.02). After stratification
      by gender, the rs17030 G allele was found to confer an increased risk for PCV in
      male (P = 0.010, OR = 1.56) but not in female. The haplotype AG defined by the
      major alleles of rs17030 and rs344555 was also associated with PCV in male (P =
      0.010, OR = 0.64). In contrast to PCV, none of the eight SNPs was significantly
      associated with neovascular AMD. This study shows an association of C3 rs17030
      with PCV in male, indicating that C3 may have an epistatic effect with gender in
      the pathogenesis of PCV. 

PMID- 25388913
TI  - High seroprevalence of echinococossis, schistosomiasis and toxoplasmosis among
      the populations in Babati and Monduli districts, Tanzania.
AB  - BACKGROUND: The neglected tropical diseases, echinococcosis, schistosomiasis and
      toxoplasmosis are all globally widespread zoonotic diseases with potentially
      harmful consequences. There is very limited data available on the prevalence of
      these infections, except for schistosmiasis, in underdeveloped countries. This
      study aimed to determine the seroprevalence of Echinococcus multilocularis,
      Schistosoma mansoni, and Toxoplasma gondii antibodies in populations from the
      Monduli and Babati districts in Tanzania. METHODS: A total of 345 blood samples
      were collected from 160 and 185 randomly selected households from Babati and
      Monduli districts, Tanzania between February and May of 2012 and analyzed them
      using the enzyme linked immunosorbent assay. The antibodies were determined using
      the NovaLisa(r) Toxoplasma gondii IgG, NovaLisa(r) Schistosoma Mansoni IgG,
      NovaLisa(r) Echinococcus IgG and NovaLisa(r) Toxoplasma gondii IgM kits (Novatec,
      Germany). RESULTS: The seropositivity estimated for E. multilocularis, S.
      mansoni, and T. gondii IgG was 11.3% (95% confidence interval (CI): 7.96-14.6),
      51.3% (95% CI: 46.0-56.5), and 57.68% (95% CI: 52.5-62.9), respectively. The
      seropositivity for T. gondii IgM was 11.3% (95% CI: 7.96-14.6). Living in the
      Monduli district was found to be the main risk factor for IgG seropositivity for
      both schistosomiasis (OR =1.94; 95% CI: 1.23-3.08; p =0.005) and toxoplasmosis
      (OR =2.09; 95% CI: 1.31-3.33; p =0.002). CONCLUSIONS: These results suggest that
      restricting disease transmission, implementing control measures, and introducing
      training projects to increase public awareness are imperative, particularly for
      the Monduli district.

PMID- 25388914
TI  - Melatonin blunts the mitochondrial/NLRP3 connection and protects against
      radiation-induced oral mucositis.
AB  - Mucositis is a common and distressing side effect of chemotherapy or radiotherapy
      that has potentially severe consequences, and no treatment is available. The
      purpose of this study was to analyze the molecular pathways involved in the
      development of oral mucositis and to evaluate whether melatonin can prevent this
      pathology. The tongue of male Wistar rats was subjected to irradiation (X-ray
      YXLON Y.Tu 320-D03 irradiator; the animals received a dose of 7.5 Gy/day for 5
      days). Rats were treated with 45 mg/day melatonin or vehicle for 21 days
      postirradiation, either by local application into their mouths (melatonin gel) or
      by subcutaneous injection. A connection between reactive oxygen species,
      generating mitochondria and the NLRP3 (NLR-related protein 3 nucleotide-binding
      domain leucine-rich repeat containing receptor-related protein 3) inflammasome,
      has been reported in mucositis. Here, we show that mitochondrial oxidative
      stress, bioenergetic impairment and subsequent NLRP3 inflammasome activation are
      involved in the development of oral mucositis after irradiation and that
      melatonin synthesized in the rat tongue is depleted after irradiation. The
      application of melatonin gel restores physiological melatonin levels in the
      tongue and prevents mucosal disruption and ulcer formation. Melatonin gel
      protects the mitochondria from radiation damage and blunts the NF-kappaB/NLRP3
      inflammasome signaling activation in the tongue. Our results suggest new
      molecular pathways involved in radiotherapy-induced mucositis that are inhibited
      by topical melatonin application, suggesting a potential preventive therapy for
      mucositis in patients with cancer.

PMID- 25388915
TI  - The dose-dependence biological effect of laser fluence on rabbit fibroblasts
      derived from urethral scar.
AB  - Two-micrometer laser vaporization resection has been used in clinic for years,
      but some patients received the treatment are still faced with excessive and
      abnormal wound repair which leads to the recurrent of urethral stricture
      eventually. Fibroblasts play a key role in the processes of "narrow
      expansion/operation-restenosis" recurring problems. Here, we investigated the
      effect of laser fluence biomodulation on urethral scar fibroblasts as well as the
      underlying mechanism. Urethral scar fibroblasts were isolated and cultured, and
      laser irradiation (2 MUm) was applied at different laser fluence or doses (0,
      0.125, 0.5, 2, 8, 32 J/cm(2)) with a single exposure in 1 day. The effect of 2
      MUm laser irradiation on cell proliferation, viability, and expression of scar
      formation related genes were investigated. Two-micrometer laser irradiation with
      intermediate dose (8 J/cm(2)) promoted scar fibroblasts proliferation and
      reactive oxygen species (ROS) production, while higher doses of 32 J/cm(2) are
      suppressive as it decreased the survival rate, viability, and proliferation of
      fibroblasts. In addition, qRT-PCR and Western blotting results both proven that
      collagen type I, collagen IV, MMP9, and CTGF display significant increase, yet
      the TGF-beta1 expression was severely reduced at intermediate dose (8 J/cm(2))
      group when compared with the others groups. Our findings suggest the scar
      formation-related genes are sensitive to intermediate laser irradiation dose, the
      most in scar fibroblasts. We revealed the bioeffect and molecular mechanism of 2
      MUm laser irradiation on rabbit urethral scar fibroblasts. Our study provides new
      insights into the mechanisms which involved in the excessive and abnormal wound
      repair of 2-MUm laser vaporization resection. These results could potentially
      contribute to further study on biological effects and application of 2-MUm laser
      irradiation in urethral stricture therapy. 

PMID- 25388916
TI  - Constitutional and somatic deletions of the Williams-Beuren syndrome critical
      region in non-Hodgkin lymphoma.
AB  - Here, we report and investigate the genomic alterations of two novel cases of Non
      Hodgkin Lymphoma (NHL) in children with Williams-Beuren syndrome (WBS), a
      multisystem disorder caused by 7q11.23 hemizygous deletion. Additionally, we
      report the case of a child with NHL and a somatic 7q11.23 deletion. Although the
      WBS critical region has not yet been identified as a susceptibility locus in NHL,
      it harbors a number of genes involved in DNA repair. The high proportion of
      pediatric NHL reported in WBS is intriguing. Therefore, the role of
      haploinsufficiency of genes located at 7q11.23 in lymphomagenesis deserves to be
      investigated. 

PMID- 25388917
TI  - Phenotypic and Genotypic Characterization of Salmonella enterica in Captive
      Wildlife and Exotic Animal Species in Ohio, USA.
AB  - The purpose of this study was to investigate the occurrence, antimicrobial
      resistance patterns, phenotypic and genotypic relatedness of Salmonella enterica
      recovered from captive wildlife host species and in the environment in Ohio, USA.
      A total of 319 samples including faecal (n = 225), feed (n = 38) and
      environmental (n = 56) were collected from 32 different wild and exotic animal
      species in captivity and their environment in Ohio. Salmonellae were isolated
      using conventional culture methods and tested for antimicrobial susceptibility
      with the Kirby-Bauer disc diffusion method. Salmonella isolates were serotyped,
      and genotyping was performed using the pulsed-field gel electrophoresis (PFGE).
      Salmonella was detected in 56 of 225 (24.9%) faecal samples; six of 56 (10.7%)
      environmental samples and six of 38 (15.8%) feed samples. Salmonella was more
      commonly isolated in faecal samples from giraffes (78.2%; 36/46), cranes (75%;
      3/4) and raccoons (75%; 3/4). Salmonella enterica serotypes of known public
      health significance including S. Typhimurium (64.3%), S. Newport (32.1%) and S.
      Heidelberg (5.3%) were identified. While the majority of the Salmonella isolates
      were pan-susceptible (88.2%; 60 of 68), multidrug-resistant strains including
      penta-resistant type, AmStTeKmGm (8.8%; six of 68) were detected. Genotypic
      diversity was found among S. Typhimurium isolates. The identification of clonally
      related Salmonella isolates from environment and faeces suggests that indirect
      transmission of Salmonella among hosts via environmental contamination is an
      important concern to workers, visitors and other wildlife. Results of this study
      show the diversity of Salmonella serovars and public health implications of human
      exposure from wildlife reservoirs.

PMID- 25388918
TI  - Effect of thyroid dysfunction and autoimmunity on pregnancy outcomes in low risk
      population.
AB  - PURPOSE: The objective of this study was to assess the effect of thyroid
      dysfunction and autoimmunity in early pregnancy on adverse pregnancy and neonatal
      outcome. METHODS: 497 pregnant women between 10 and 12 gestational age were
      invited who were attending for their first antenatal visit and asked to perform
      blood tests for thyroid function and antithyroid peroxidase antibodies. A total
      of 395 women were recruited in the present study. Cases were classified into four
      groups according to thyroid function and anti-TPO results. The pregnancy outcomes
      included gestational diabetes mellitus, preeclampsia, preterm delivery, cesarean
      rate, small for gestational age, low birth weight. RESULTS: 2.5-(OR 2.5, 95% CI
      1.06-5.89) and 4.8-(OR 4.85, 95% CI 1.89-12.42) fold increase in preterm delivery
      was detected in groups with isolated anti-TPO positivity and subclinic
      hypothyroidism with anti-TPO positivity compared to reference group,
      respectively. No association was found between thyroid dysfunction and anti-TPO
      positivity with gestational diabetes, preeclampsia, cesarean rates, low birth
      weight and small for gestational age neonates. CONCLUSION: Pregnant women with
      anti-TPO antibody positivity alone or with subclinic hypothyroidism were more
      likely to experience a spontaneous preterm delivery.

PMID- 25388919
TI  - A stepwise cesarean section for placenta percreta: effective only for "separable"
      placenta percreta?

PMID- 25388920
TI  - Intraoperative rupture of benign mucinous cystadenoma does not increase its
      recurrence rate.
AB  - PURPOSE: Laparoscopy has become the standard of care in the management of ovarian
      benign mucinous cystadenomas. One concern of the operative approach is the risk
      of recurrence. A previous study has found intraoperative cyst rupture and
      cystectomy to be the risk factors for recurrence. Our objective was to assess the
      incidence and risk factors for recurrence of benign mucinous cystadenomas after
      surgical removal. METHODS: We conducted a retrospective analysis of all cases of
      patients who underwent removal of benign mucinous cystadenomas by either
      cystectomy or adnexectomy in our institution between December 2006 and June 2013.
      RESULTS: 722 women underwent surgical treatment for benign ovarian cysts in that
      time period, out of which 38 women (5.2%) had benign mucinous cystadenomas
      confirmed by pathologic examination. Most of the patients underwent laparoscopy
      (94.7%). Half of the patients underwent cystectomy, and the other half underwent
      adnexectomy. One patient underwent re-operation due to cyst recurrence. This
      patient initially underwent laparoscopic cystectomy, during which intraoperative
      cyst rupture did not occur. CONCLUSION: Recurrence of benign mucinous
      cystadenomas was uncommon and was not associated with intraoperative cyst
      rupture.

PMID- 25388921
TI  - Response to: a stepwise cesarean section for placenta percreta: effective only
      for "separable" placenta percreta?

PMID- 25388922
TI  - Is gestational diabetes mellitus an independent risk factor for macrosomia: a
      meta-analysis?
AB  - PURPOSE: The aim of our meta-analysis was to explore whether gestational diabetes
      mellitus (GDM) is an independent risk factor for macrosomia or not. METHODS:
      Three databases were systematically reviewed and reference lists of relevant
      articles were checked. Meta-analysis of published epidemiological studies (cohort
      and case-control studies) comparing whether GDM was associated with macrosomia.
      Calculations of pooled estimates were conducted in random-effect models.
      Heterogeneity was tested by using Chi square test and I (2) statistics.
      Publication bias was estimated from Egger's test (linear regression method) and
      Begg's test (rank correlation method). RESULTS: Twelve studies met the inclusion
      criteria, including five cohort studies and seven case-control studies. The meta
      analysis showed that GDM was associated with macrosomia independent of other risk
      factors. The adjusted odds ratio was 1.71, 95% CI (1.52, 1.94) in random-effect
      model, stratified analyses showed no differences regarding different study
      design, quality grade, definition of macrosomia, location of study and number of
      confounding factors adjusted for. There was no indication of a publication bias
      either from the result of Egger's test or Begg's test. CONCLUSION: Our findings
      indicate that GDM should be considered as an independent risk factor for newborn
      macrosomia. To adequately evaluate the clinical evolution of GDM need to be
      carefully assessed and monitored.

PMID- 25388923
TI  - Plasticity to simulated shade is associated with altitude in structured
      populations of Arabidopsis thaliana.
AB  - Plants compete for photosynthesis light and induce a shade avoidance syndrome
      (SAS) that confers an important advantage in asymmetric competition for light at
      high canopy densities. Shade plasticity was studied in a greenhouse experiment
      cultivating Arabidopsis thaliana plants from 15 populations spread across an
      altitudinal gradient in the northeast area of Spain that contain a high genetic
      variation into a reduced geographical range. Plants were exposed to sunlight or
      simulated shade to identify the range of shade plasticity. Fourteen vegetative,
      flowering and reproductive traits were measured throughout the life cycle. Shade
      plasticity in flowering time and dry mass was significantly associated with the
      altitude of population origin. Plants from coastal populations showed higher
      shade plasticity indexes than those from mountains. The altitudinal variation in
      flowering leaf plasticity adjusted negatively with average and minimum
      temperatures, whereas dry mass plasticity was better explained by negative
      regressions with the average, maximum and minimum temperatures, and by a positive
      regression with average precipitation of the population origin. The lack of an
      altitudinal gradient for the widest number of traits suggests that shade light
      could be a driver explaining the distribution pattern of individuals in smaller
      geographical scales than those explored here. 

PMID- 25388924
TI  - pi-pi Stacking induced enhanced molecular solubilization, singlet oxygen
      production, and retention of a photosensitizer loaded in thermosensitive
      polymeric micelles.
AB  - Cancer photodynamic therapy (PDT) by photosensitizers (PS)-loaded polymeric
      micelles (PM) is hampered by the tendency of PS to aggregate in PM and/or by
      premature release of PS in the blood circulation. In the present study, aromatic
      thermosensitive PM, characterized by pi-pi stacking interaction, are used to
      encapsulate an axially solketal-substituted silicon phthalocyanine (Si(sol)2 Pc)
      with enhanced loading capacity, smaller size, and significantly improved
      retention of Si(sol)2 Pc compared with systems based on thermosensitive PM
      lacking aromatic groups. Interestingly, Si(sol)2 Pc is much less prone to
      aggregation in the aromatic PM, i.e., the amount of Si(sol)2 Pc that could be
      encapsulated without aggregation is 330 times higher in the aromatic PM than in
      the nonaromatic PM. Furthermore, Si(sol)2 Pc in the aromatic PM in a molecularly
      dissolved (non-aggregated) form displays three times more efficient singlet
      oxygen production than Si(sol)2 Pc aggregated in the non-aromatic PM. As a
      result, the photocytotoxicity of Si(sol)2 Pc-loaded aromatic PM to B16F10 cells
      is increased, compared with that of the non-aromatic PM, while no significant
      cytotoxicity is observed in the dark. Fluorescence-activated cell sorting (FACS)
      and confocal laser scanning microscopy (CLSM) analysis shows cell uptake of
      Si(sol)2 Pc loaded in the aromatic PM, and the Si(sol)2 Pc is taken up by the
      cells together with the micelles. The efficient singlet oxygen production of
      Si(sol)2 Pc dissolved in the aromatic PM makes it an interesting formulation for
      cancer PDT. 

PMID- 25388925
TI  - Incretins or anti-incretins? A new model for the "entero-pancreatic axis".
AB  - The role of incretins in glucose homeostasis is well known. Yet, in recent years,
      the sustained weight loss and rapid glycemic control following bariatric surgery
      has challenged our understanding of the intestinal-pancreatic interaction. This
      in turn led to the introduction of metabolic surgery, an innovative medical
      discipline in which a surgical manipulation of the gastrointestinal tract (e. g.,
      through a Roux-en-Y gastric bypass, RYGB, or Bilio-Pancreatic-Diversion, BPD)
      yields a sustained remission of diabetes mellitus. The pathophysiological
      background of this metabolic effect is, amongst other things, based on the anti
      incretin theory. This theory postulates that in addition to the well-known
      incretin effect, nutrient passage through the GI-tract could also activate
      negative feedback mechanisms (anti-incretins) to balance the effects of incretins
      and other postprandial glucose-lowering mechanisms (i. e., suppression of
      ghrelin, glucagon, and hepatic glucose production via activation of nutrient
      sensing). This in turn prevents postprandial hyperinsulinemic hypoglycemia. The
      bypass of the duodenum, the entire jejunum and the first portion of the ileum by
      BPD induce normalization of peripheral insulin sensitivity, while the bypass of a
      shorter intestinal tract by RYGB mainly improves the hepatic insulin sensitivity.
      In addition, RYGB greatly increases insulin secretion. Therefore, metabolic
      surgery highlights the important role of the small intestine in glucose
      homeostasis, while until few years ago, it was only the pancreas and the liver
      that were thought to represent the regulatory organs for glucose disposal.

PMID- 25388926
TI  - Dry powder inhalers in COPD, lung inflammation and pulmonary infections.
AB  - INTRODUCTION: The number of pulmonary diseases that are effectively treated by
      aerosolized medicine continues to grow. AREAS COVERED: These diseases include
      chronic obstructive pulmonary disease (COPD), lung inflammatory diseases (e.g.,
      asthma) and pulmonary infections. Dry powder inhalers (DPIs) exhibit many unique
      advantages that have contributed to the incredible growth in the number of DPI
      pharmaceutical products. To improve the performance, there are a relatively large
      number of DPI devices available for different inhalable powder formulations. The
      relationship between formulation and inhaler device features on performance of
      the drug-device combination product is critical. Aerosol medicine products are
      drug-device combination products. Device design and compatibility with the
      formulation are key drug-device combination product aspects in delivering drugs
      to the lungs as inhaled powders. In addition to discussing pulmonary diseases,
      this review discusses DPI devices, respirable powder formulation and their
      interactions in the context of currently marketed DPI products used in the
      treatment of COPD, asthma and pulmonary infections. EXPERT OPINION: There is a
      growing line of product options available for patients in choosing inhalers for
      treatment of respiratory diseases. Looking ahead, combining nanotechnology with
      optimized DPI formulation and enhancing device design presents a promising future
      for DPI development.

PMID- 25388927
TI  - Congenital heart disease in the Niger Delta region of Nigeria: a four-year
      prospective echocardiographic analysis.
AB  - INTRODUCTION: Echocardiographic evaluation remains the gold standard for the
      diagnosis of structural cardiac disease. No previous prospective studies have
      been done on the prevalence of congenital heart disease (CHD) in the Niger Delta
      area. This study was done to determine the frequency and pattern of congenital
      heart disease, using echocardiography as a diagnostic tool. METHODS: All patients
      presenting to the Paediatric Cardiology clinics of two centres, the University of
      Port Harcourt Teaching Hospital and the Paediatric Care Hospital between April
      2009 and March 2013, were recruited and all had echocardiography performed.
      RESULTS: Prevalence of CHD in this study was 14.4 per 1 000 children; 277 (83.4%)
      of the patients had acyanotic CHD and 55 (16.6%) had cyanotic CHD. Ventricular
      septal defect and tetralogy of Fallot were the commonest acyanotic and cyanotic
      heart defects, respectively. CONCLUSION: The high prevalence of CHD in this study
      is the highest in the country and Africa, and may be attributable to the
      increased oil spillage and gas flaring from petroleum exploitation in this
      region.

PMID- 25388929
TI  - Is open access sufficient? A review of the quality of open-access nursing
      journals.
AB  - The present study aims to review the quality of open-access nursing journals
      listed in the Directory of Open Access Journals that published papers in 2013
      with a nursing focus, written in English, and were freely accessible. Each
      journal was reviewed in relation to their publisher, year of commencement, number
      of papers published in 2013, fee for publication, indexing, impact factor, and
      evidence of requirements for ethics and disclosure statements. The quality of the
      journals was assessed by impact factors and the requirements for indexing in
      PubMed. A total of 552 were published in 2013 in the 19 open-access nursing
      journals that met the inclusion criteria. No journals had impact factors listed
      in Web of Knowledge, but three had low Scopus impact factors. Only five journals
      were indexed with PubMed. The quality of the 19 journals included in the review
      was evaluated as inferior to most subscription-fee journals. Mental health
      nursing has some responsibility to the general public, and in particular,
      consumers of mental health services and their families, for the quality of papers
      published in open-access journals. The way forward might involve dual-platform
      publication or a process that enables assessment of how research has improved
      clinical outcomes. 

PMID- 25388928
TI  - Molecular epidemiology of rhinoviruses in Cyprus over three consecutive seasons.
AB  - Human rhinoviruses (HRVs) are widespread respiratory pathogens and a major cause
      of acute respiratory tract infections. The aim of this study was to investigate
      the molecular epidemiology of rhinovirus infections in children in Cyprus over
      three consecutive winter seasons. From a total of 116 rhinovirus-positive
      samples, 68 were sequenced in the 5'-UTR and VP4/VP2 regions. Thirty-six (52.9%)
      samples were identified as HRV-A and 27 (39.7%) as HRV-C, with only five (7.4%)
      samples belonging to the HRV-B species. Of these, a total of 46 different
      genotypes were identified. In the VP2/VP4 phylogenetic tree all strains clustered
      in three different well-defined clades, whereas the 5'-UTR tree exhibited clades
      with a mixed clustering of HRV-A and HRV-C strains reflecting the evolutionary
      history of recombination between HRV-A and HRV-C that has been observed
      previously. In summary, a high intra- and inter-season diversity of HRV types was
      observed. Despite its geographical isolation the frequency of HRV species in
      Cyprus is comparable to that reported in other regions of the world supporting
      the concept of an unrestricted global circulation. This study assesses, for the
      first time, the epidemiology of rhinovirus infections in Cypriot children and
      will be helpful to clinicians and researchers interested in the treatment and
      control of viral respiratory tract infections.

PMID- 25388930
TI  - Rabies vaccine-associated thrombotic thrombocytopenic purpura.

PMID- 25388935
TI  - FIrpic: archetypal blue phosphorescent emitter for electroluminescence.
AB  - FIrpic is the most investigated bis-cyclometallated iridium complex in particular
      in the context of organic light emitting diodes (OLEDs) because of its attractive
      sky-blue emission, high emission efficiency, and suitable energy levels. In this
      Perspective we review the synthesis, structural characterisations, and key
      properties of this emitter. We also survey the theoretical studies and summarise
      a series of selected monochromatic electroluminescent devices using FIrpic as the
      emitting dopant. Finally we highlight important shortcomings of FIrpic as an
      emitter for OLEDs. Despite the large body of work dedicated to this material, it
      is manifest that the understanding of photophysical and electrochemical processes
      are only broadly understood mainly because of the different environment in which
      these properties are measured, i.e., isolated molecules in solvent vs. device. 

PMID- 25388934
TI  - Supervised exercise improves cutaneous reinnervation capacity in metabolic
      syndrome patients.
AB  - OBJECTIVE: Unmyelinated cutaneous axons are vulnerable to physical and metabolic
      injury, but also capable of rapid regeneration. This balance may help determine
      risk for peripheral neuropathy associated with diabetes or metabolic syndrome.
      Capsaicin application for 48 hours induces cutaneous fibers to die back into the
      dermis. Regrowth can be monitored by serial skin biopsies to determine
      intraepidermal nerve fiber density (IENFD). We used this capsaicin axotomy
      technique to examine the effects of exercise on cutaneous regenerative capacity
      in the setting of metabolic syndrome. METHODS: Baseline ankle IENFD and 30-day
      cutaneous regeneration after thigh capsaicin axotomy were compared for
      participants with type 2 diabetes (n = 35) or metabolic syndrome (n = 32) without
      symptoms or examination evidence of neuropathy. Thirty-six participants (17 with
      metabolic syndrome) then joined twice weekly observed exercise and lifestyle
      counseling. Axotomy regeneration was repeated in month 4 during this
      intervention. RESULTS: Baseline distal leg IENFD was significantly reduced for
      both metabolic syndrome and diabetic groups. With exercise, participants
      significantly improved exercise capacity and lower extremity power. Following
      exercise, 30-day reinnervation rate improved (0.051 +/- 0.027 fibers/mm/day
      before vs 0.072 +/- 0.030 after exercise, p = 0.002). Those who achieved
      improvement in more metabolic syndrome features experienced a greater degree of
      30-day reinnervation (p < 0.012). INTERPRETATION: Metabolic syndrome was
      associated with reduced baseline IENFD and cutaneous regeneration capacity
      comparable to that seen in diabetes. Exercise-induced improvement in metabolic
      syndrome features increased cutaneous regenerative capacity. The results
      underscore the potential benefit to peripheral nerve function of a behavioral
      modification approach to metabolic improvement.

PMID- 25388936
TI  - Titanyl phthalocyanine ambipolar thin film transistors making use of carbon
      nanotube electrodes.
AB  - The capability of efficiently injecting charge carriers into organic films and
      finely tuning their morphology and structure is crucial to improve the
      performance of organic thin film transistors (OTFTs). In this work, we
      investigate OTFTs employing carbon nanotubes (CNTs) as the source-drain
      electrodes and, as the organic semiconductor, thin films of titanyl
      phthalocyanine (TiOPc) grown by supersonic molecular beam deposition (SuMBD).
      While CNT electrodes have shown an unprecedented ability to improve charge
      injection in OTFTs, SuMBD is an effective technique to tune film morphology and
      structure. Varying the substrate temperature during deposition, we were able to
      grow both amorphous (low substrate temperature) and polycrystalline (high
      substrate temperature) films of TiOPc. Regardless of the film morphology and
      structure, CNT electrodes led to superior charge injection and transport
      performance with respect to benchmark Au electrodes. Vacuum annealing of
      polycrystalline TiOPc films with CNT electrodes yielded ambipolar OTFTs. 

PMID- 25388937
TI  - Probing dynamic myocardial microstructure with cardiac magnetic resonance
      diffusion tensor imaging.
AB  - This article is an invited editorial comment on the paper entitled "In vivo
      cardiovascular magnetic resonance diffusion tensor imaging shows evidence of
      abnormal myocardial laminar orientations and mobility in hypertrophic
      cardiomyopathy" by Ferreira et al., and published as Journal of Cardiovascular
      Magnetic Resonance 2014; 16:87. 

PMID- 25388938
TI  - [urinary tract infections].

PMID- 25388939
TI  - Pharmacokinetic study of aldoxorubicin in patients with solid tumors.
AB  - Introduction Aldoxorubicin, a prodrug of doxorubicin, binds covalently to serum
      albumin in the bloodstream and accumulates in tumors. Aldoxorubicin can be
      administered at doses several-fold higher than doxorubicin can, without
      associated acute cardiotoxicity. Purpose This study fully evaluated the
      pharmacokinetic profile of aldoxorubicin (serum and urine). Methods Eighteen
      patients with advanced solid tumors received aldoxorubicin 230 or 350 mg/m(2)
      (equivalent in drug load to doxorubicin at doses of 170 or 260 mg/m(2),
      respectively) once every 21 days. Blood samples were taken in cycle 1 before
      aldoxorubicin infusion, and at 5, 15, 30, and 60 min, and at 2, 4, 8, 12, 16, 24,
      48, and 72 h after infusion. Urine samples were taken in cycle 1 at 24, 48, and
      72 h after infusion. Limited blood sampling was done in cycle 3, before
      aldoxorubicin infusion, and at 60 min and at 2, 4, and 8 h after infusion.
      Results The long mean half-life (20.1-21.1 h), narrow mean volume of distribution
      (3.96-4.08 L/m(2)), and slow mean clearance rate (0.136-0.152 L/h/m(2)) suggest
      that aldoxorubicin is stable in circulation and does not accumulate readily in
      body compartments outside of the bloodstream. Very little doxorubicin and its
      major metabolite doxorubicinol, which has been implicated in doxorubicin
      associated cardiotoxicity, are excreted in urine. This might explain the lack of
      cardiotoxicity observed thus far with aldoxorubicin. Conclusions Our findings
      support dosing and administration schemas used in an ongoing phase 3 clinical
      study of aldoxorubicin in soft tissue sarcoma, and phase 2 clinical studies in
      small cell lung cancer, glioblastoma, and Kaposi's sarcoma.

PMID- 25388940
TI  - Phase 2 study of CT-322, a targeted biologic inhibitor of VEGFR-2 based on a
      domain of human fibronectin, in recurrent glioblastoma.
AB  - VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis.
      CT-322, a pegylated protein engineered from the 10th type III human fibronectin
      domain, binds the VEGFR-2 extracellular domain with high specificity and affinity
      to block VEGF-induced VEGFR-2 signaling. This study evaluated CT-322 in an open
      label run-in/phase 2 setting to assess its efficacy and safety in recurrent
      glioblastoma. Eligible patients had 1st, 2nd or 3rd recurrence of glioblastoma
      with measurable tumor on MRI and no prior anti-angiogenic therapy. The initial CT
      322 dose was 1 mg/kg IV weekly, with plans to escalate subsequent patients to 2
      mg/kg weekly if tolerated; within each CT-322 dose cohort, patients were
      randomized to +/-irinotecan IV semiweekly. The primary endpoint was 6-month
      progression-free survival (PFS-6). Sixty-three patients with a median age of 56
      were treated, the majority at first recurrence. One-third experienced serious
      adverse events, of which four were at least possibly related to study treatment
      (two intracranial hemorrhages and two infusion reactions). Twenty-nine percent of
      subjects developed treatment-emergent hypertension. The PFS-6 rate in the CT-322
      monotherapy groups was 18.6 and 0.0 % in the 1 and 2 mg/kg treatment groups,
      respectively; results from the 2 mg/kg group indicated that the null hypothesis
      that PFS-6 <=12 % could not be rejected. The study was terminated prior to
      reaching the planned enrollment for all treatment groups because data from the
      completed CT-322 2 mg/kg monotherapy treatment arm revealed insufficient
      efficacy. Despite biological activity and a tolerable side effect profile, CT-322
      failed to meet the prespecified threshold for efficacy in recurrent glioblastoma.

PMID- 25388941
TI  - Dynamics of pulmonary venous flow in fetuses with intrauterine growth
      restriction.
AB  - OBJECTIVE: To test the hypothesis that the pulmonary vein pulsatility index
      (PVPI) is higher in fetuses with growth restriction (IUGR) than in normal
      fetuses. METHODS: Twenty-two fetuses with IUGR and twenty-one (21) fetuses with
      appropriate growth for gestational age from healthy mothers were studied. PVPI
      was calculated by Doppler echocardiography [maximal velocity (systolic or
      diastolic peak) - pre-systolic peak / mean velocity]. Obstetric ultrasound was
      used to assess fetal biometry and Doppler to assess the uterine, umbilical and
      middle cerebral arteries PI. Statistical analysis used t test and Pearson's
      correlation. RESULTS: Mean gestational age was 31.5 +/- 2.1 weeks in the control
      group and 31.4 +/- 3.1 weeks in IUGR (P = 0.91). The PI of uterine and umbilical
      arteries were higher in IUGR than in controls (P < 0.001). Mean PVPI in IUGR
      fetuses was 1.31 +/- 0.41, and in controls it was 0.83 +/- 0.11 (P < 0.001).
      CONCLUSION: The pulsatility index of pulmonary venous flow in fetuses with growth
      restriction is higher than in normal fetuses, probably as a result of left atrial
      dynamics alteration secondary or not to fetal left ventricular diastolic
      dysfunction. (c) 2014 John Wiley & Sons, Ltd.

PMID- 25388942
TI  - Ultrasound-based diagnosis for the cervical lymph nodes in a tuberculosis-endemic
      area.
AB  - OBJECTIVES/HYPOTHESIS: No previous ultrasound (US) studies have investigated the
      diagnostic accuracy of specific US-based diagnostic protocol for cervical lymph
      node (LN) lesions in a tuberculosis-endemic area. This study aimed to assess the
      accuracy of US-based diagnosis of cervical LNs in a tuberculosis-endemic area.
      STUDY DESIGN: This was a retrospective cohort study. METHODS: We enrolled 495
      consecutive patients who underwent US examination of the LNs in the neck. A
      single radiologist carried out the US examination, and established a US-based
      diagnosis at the time of the examination in each of the patients. We calculated
      the diagnostic accuracy of US for LNs in the neck by using the final results as a
      reference standard. RESULTS: Of 476 study cases, the number of tuberculous,
      nontuberculous benign, malignant, and indeterminate US category cases was 74,
      224, 152, and 26, respectively. Confirmed diagnoses in these cases were as
      follow: tuberculous LN (n = 69), nontuberculous benign LN (n = 249), and
      malignant LN (n = 158). The sensitivity, specificity, positive and negative
      predictive values, and accuracy of tuberculous, malignant, and nontuberculous
      benign US categories were 90.9%, 96.4%, 81.1%, 98.4%, and 95.6%; 92.8%, 96.6%,
      93.4%, 96.3%, and 95.3%; and 92.2%, 95.0%, 95.1%, 92.0%, and 93.6%, respectively.
      All US categories showed a high sensitivity and specificity. CONCLUSIONS: The
      present US-based diagnostic protocol for cervical LNs in a tuberculosis-endemic
      area may be useful. LEVEL OF EVIDENCE: 4.

PMID- 25388943
TI  - Yeast population dynamics reveal a potential 'collaboration' between
      Metschnikowia pulcherrima and Saccharomyces uvarum for the production of reduced
      alcohol wines during Shiraz fermentation.
AB  - The wine sector is actively seeking strategies and technologies that facilitate
      the production of wines with lower alcohol content. One of the simplest
      approaches to achieve this aim would be the use of wine yeast strains which are
      less efficient at transforming grape sugars into ethanol; however, commercial
      wine yeasts have very similar ethanol yields. We recently demonstrated that
      Metschnikowia pulcherrima AWRI1149 was able to produce wine with reduced alcohol
      concentration when used in sequential inoculation with a wine strain of
      Saccharomyces cerevisiae. Here, different inoculation regimes were explored to
      study the effect of yeast population dynamics and potential yeast interactions on
      the metabolism of M. pulcherrima AWRI1149 during fermentation of non-sterile
      Shiraz must. Of all inoculation regimes tested, only ferments inoculated with M.
      pulcherrima AWRI1149 showed reduced ethanol concentration. Population dynamics
      revealed the presence of several indigenous yeast species and one of these,
      Saccharomyces uvarum (AWRI 2846), was able to produce wine with reduced ethanol
      concentration in sterile conditions. Both strains however, were inhibited when a
      combination of three non-Saccharomyces strains, Hanseniaspora uvarum AWRI863,
      Pichia kluyveri AWRI1896 and Torulaspora delbrueckii AWRI2845 were inoculated
      into must, indicating that the microbial community composition might impact on
      the growth of M. pulcherrima AWRI1149 and S. uvarum AWRI 2846. Our results
      indicate that mixed cultures of M. pulcherrima AWRI1149 and S. uvarum AWRI2846
      enable an additional reduction of wine ethanol concentration compared to the same
      must fermented with either strain alone. This work thus provides a foundation to
      develop inoculation regimes for the successful application of non-cerevisiae
      yeast to the production of wines with reduced alcohol. 

PMID- 25388944
TI  - Poly(ADP-ribose) polymerase 1 activation links ischemic acute kidney injury to
      interstitial fibrosis.
AB  - Inactivation of poly(ADP-ribose) polymerase 1 (PARP1) has been found to be
      protective in several disease models; however, the role of PARP1 in acute kidney
      injury-induced interstitial fibrosis has not been studied. Herein, we tested
      whether PARP1 inactivation by treatment with PJ34 (a PARP1 inactivator; 10 mg/kg
      body weight/day, intraperitoneal implantation of a miniosmotic pump at 2 days
      after the onset) contributed to the decrease in interstitial fibrosis induced by
      ischemia-reperfusion injury (IRI) in mouse kidneys. IRI increased PARP1
      activation represented by poly(ADP-ribose) expression from 4 to 16 days
      postinjury, whereas treatment with PJ34 at 2 days after the onset efficaciously
      abolished the increase in PARP1 activation at 4, 8 and 16 days after IRI.
      Pharmacological inactivation of PARP1 significantly reduced interstitial fibrosis
      as represented by the collagen deposition and transforming growth factor-beta1
      level at 8 and 16 days after IRI. Consistent with collagen deposition,
      myofibroblast activation represented by alpha-smooth muscle actin expression was
      also reduced by PARP1 inactivation at 8 and 16 days after IRI. Furthermore, IRI
      enhanced macrophage influx, but PARP1 inactivaton remarkably reduced macrophage
      influx for 4 through 16 days after the injury. Among the chemoattractants for
      monocytes/macrophages and neutrophils, monocyte chemotactic protein-1 (MCP-1)
      production in IRI kidneys was significantly reduced by PARP1 inactivation from 4
      to 16 days postinjury. These data demonstrate that PARP1 activation contributes
      to IRI-induced MCP-1 production and in turn to macrophage influx, resulting in
      the promotion of interstitial fibrosis.

PMID- 25388946
TI  - HIV risks vary according to type of sex work in a cross-sectional survey from
      Nagaland, India.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is a significant problem
      among female sex workers (FSWs) in Nagaland, India. Place of solicitation and sex
      vary considerably in this context. The aim of this study was to investigate the
      relationship between categories of sex work and HIV risks. METHODS: In 2009 a
      survey was undertaken among 417 FSWs in Dimapur, Nagaland using an interviewer
      administered questionnaire and blood and urine samples. Using this data, we
      constructed a typology of sex work by combining usual place of solicitation and
      place of sex, and examined variations in demographics, sex work patterns,
      sexually transmitted infections (STIs) and HIV prevalence across typology
      categories. Binary logistic regression analyses were done to examine the
      association between category of sex work and HIV, STIs, and condom use. RESULTS:
      By combining place of solicitation with place of sex, seven distinct categories
      of sex work emerged. The largest category were women who usually solicited in a
      public place and had sex in a rented room or lodge (31.7%, n = 132). One-tenth of
      participants were HIV positive (10.3%) and 35.4% had at least one STI (reactive
      syphilis serology, gonorrhoea or chlamydia). FSWs who both solicited and
      entertained in a rented room or lodge (OR = 13.3; 95% CI 2.2, 81.5) and those who
      solicited by phone and had sex in a rented room or lodge (OR = 6.3; 95% CI 1.0,
      38.0) were more likely to be HIV positive compared to home-based FSWs. Women who
      both solicited and entertained in public (OR = 6.7; 95% CI 1.6, 28.0) and who
      solicited in public and entertained in a rented room or lodge (OR = 2.5; 95% CI
      1.1, 6.0) were more likely to test positive for an STI compared to home-based
      FSWs. CONCLUSION: The results indicate that different categories of sex work are
      associated with different HIV and STI risk profiles. Local contextual
      understanding of the different types of sex work and the associated levels of
      risk assist NGOs to target their interventions more effectively and efficiently
      in order to reduce STI and HIV prevalence among FSWs and their clients.

PMID- 25388947
TI  - Verification of impact of morning showering and mist sauna bathing on human
      physiological functions and work efficiency during the day.
AB  - Recently, a growing number in Japan are switching to taking baths in the morning
      (morning bathing). However, the effects of the morning bathing on human
      physiological functions and work efficiency have not yet been revealed. Then, we
      hypothesized that the effect of morning bathing on physiological functions would
      be different from those of night bathing. In this study, we measured the
      physiological functions and work efficiency during the day following the morning
      bathing (7:10-7:20) including showering, mist sauna bathing, and no bathing as a
      control. Ten male healthy young adults participated in this study as the
      subjects. We evaluated the rectal temperature (Tre), skin temperature (Tsk),
      heart rate (HR), heart rate variability (HRV), blood pressure (BP), the relative
      power density of the alpha wave (alpha-wave ratio) of electroencephalogram, alpha
      attenuation coefficient (AAC), and the error rate of the task performance. As a
      result, we found that the HR after the mist sauna bathing was significantly lower
      than those after no bathing rest 3 (11:00). Furthermore, we verified that the
      alpha-wave ratio of the Pz after the mist sauna bathing was significantly lower
      than those after no bathing during the task 6 (15:00). On the other hand, the
      alpha-wave ratio of the Pz after the mist sauna bathing was significantly higher
      than those after showering during the rest 3 (11:00). Tsk after the mist sauna
      bathing was higher than those after the showering at 9:00 and 15:00. In addition,
      the error rate of the task performance after the mist sauna bathing was lower
      than those after no bathing and showering at 14:00. This study concludes that a
      morning mist sauna is safe and maintains both skin temperature compared to other
      bathing methods. Moreover, it is presumed that the morning mist sauna bathing
      improves work efficiency comparing other bathing methods during the task period
      of the day following the morning bathing. 

PMID- 25388945
TI  - A comparison of chronic AICAR treatment-induced metabolic adaptations in red and
      white muscles of rats.
AB  - The signaling molecule 5'-AMP-activated protein kinase plays a pivotal role in
      metabolic adaptations. Treatment with 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofranoside (AICAR) promotes the expression of metabolic regulators and
      components involved in glucose uptake, mitochondrial biogenesis, and fatty acid
      oxidation in skeletal muscle cells. Our aim was to determine whether AICAR
      induced changes in metabolic regulators and components were more prominent in
      white or red muscle. Rats were treated with AICAR (1 mg/g body weight/day) for 14
      days, resulting in increased expression levels of nicotinamide
      phosphoribosyltransferase (NAMPT), peroxisome proliferator-activated receptor
      gamma coactivator-1alpha (PGC-1alpha), glucose transporter 4 proteins, and
      enhanced mitochondrial biogenesis. These changes were more prominent in white
      rather than red gastrocnemius muscle or were only observed in the white
      gastrocnemius. Our results suggest that AICAR induces the expression of metabolic
      regulators and components, especially in type II (B) fibers.

PMID- 25388948
TI  - A note on the evolution of the daily pattern of thermal comfort-related
      micrometeorological parameters in small urban sites in Athens.
AB  - Studies on human thermal comfort in urban areas typically quantify and assess the
      influence of the atmospheric parameters studying the values and their patterns of
      the selected index or parameter. In this paper, the interpretation tools are the
      first derivative of the selected parameters (?Parameter/?t) and the violin plots.
      Using these tools, the effect of sites' configuration on thermal conditions was
      investigated. Both derivatives and violin plots indicated the ability of
      vegetation to act as a buffer to the rapid changes of air temperature, mean
      radiant temperature, and the physiologically equivalent temperature (PET). The
      study is focused on the "thermal extreme" seasons of winter (December, January,
      and February) and summer (June, July, and August) during a 3-year period of
      measurements in five selected sites under calm wind and sunny conditions.
      According to the results, the absence of vegetation leads to high derivative
      values whereas the existence of dense vegetation tends to keep the parameters'
      values relatively low, especially under hot weather conditions. 

PMID- 25388949
TI  - Functional equivalence, competitive hierarchy and facilitation determine species
      coexistence in highly invaded grasslands.
AB  - Alien and native plant species often differ in functional traits. Trait
      differences could lead to niche differences that minimize competitive
      interactions and stabilize coexistence. However, trait differences could also
      translate into average fitness differences, leading to a competitive hierarchy
      that prevents coexistence. We tested whether trait differences between alien and
      native species translated into average fitness or stabilizing niche differences,
      and whether competition could explain observed coexistence within invaded
      grassland communities (New Zealand). Trait differences reflected marked
      competitive hierarchy, suggesting average fitness differences. Species
      coexistence was determined by a trade-off between species susceptibility to
      herbivory vs competitive hierarchy and facilitation. Importantly, although aliens
      and natives differed in their trait values, they did not differ in their
      competitive response, highlighting the importance of equalizing mechanisms in
      structuring invaded communities. Only a few alien species with a particular set
      of traits were able to jeopardize species coexistence when grazing was ceased.
      Our study explains why some alien species coexist with natives, whereas others
      have strong impacts on native communities. It highlights that trait differences
      can underlie several coexistence processes and that the demonstration of trait
      differences between aliens and natives is only a first step to understanding the
      role of biotic interactions in structuring invaded communities. 

PMID- 25388950
TI  - Proven Epstein-Barr encephalitis with negative EBV-DNA load in cerebrospinal
      fluid after allogeneic hematopoietic stem cell transplantation in a child with
      acute lymphoblastic leukemia.
AB  - We report a case of EBV encephalitis in a seven-yr-old child with Ph+ ALL. Two
      months after an allogeneic HSCT from his HLA mismatched mother, the patient
      showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain
      MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood
      and CSF PCR analyses were negative for the most common viruses involved in
      immunocompromised patients including EBV. A cerebral biopsy was performed, which
      showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis
      performed on brain tissue was positive only for the EBV genome, while extensive
      investigations for other viral infections were negative. The patient's
      neurological symptoms rapidly worsened and he died two months later. This case
      report suggests that in patients presenting neurological and radiological signs
      of encephalitis after an HSCT, an EBV involvement should be considered, even in
      the absence of CSF and blood PCR virus detection. 

PMID- 25388952
TI  - Systematic review and meta-analysis comparing three techniques for pancreatic
      remnant closure following distal pancreatectomy.
AB  - BACKGROUND: Established closure techniques for the pancreatic remnant after
      distal pancreatectomy include stapler, suture and anastomotic closure. However,
      controversy remains regarding the ideal technique; therefore, the aim of this
      study was to compare closure techniques and risk of postoperative pancreatic
      fistula (POPF). METHODS: A systematic review was carried out according to PRISMA
      guidelines for studies published before January 2014 that compared at least two
      closure techniques for the pancreatic remnant in distal pancreatectomy. A random
      effects model was constructed using weighted odds ratios (ORs). RESULTS: Thirty
      seven eligible studies matched the inclusion criteria and 5252 patients who
      underwent distal pancreatectomy were included. The primary outcome measure, the
      POPF rate, ranged 0 from to 70 per cent. Meta-analysis of the 31 studies
      comparing stapler versus suture closure showed that the stapler technique had a
      significantly lower rate of POPF, with a combined OR of 0.77 (95 per cent c.i.
      0.61 to 0.98; P = 0.031). Anastomotic closure was associated with a significantly
      lower POPF rate than suture closure (OR 0.55, 0.31 to 0.98; P = 0.042). Combined
      stapler and suture closure had significantly lower POPF rates than suture closure
      alone, but no significant difference compared with stapler closure alone.
      CONCLUSION: The use of stapler closure or anastomotic closure for the pancreatic
      remnant after distal pancreatectomy significantly reduces POPF rates compared
      with suture closure. The combination of stapler and suture closure shows
      superiority over suture closure alone.

PMID- 25388951
TI  - ARGONAUTE 6 bridges transposable element mRNA-derived siRNAs to the establishment
      of DNA methylation.
AB  - Transposable elements (TEs) generate mutations and chromosomal instability when
      active. To repress TE activity, eukaryotic cells evolved mechanisms to both
      degrade TE mRNAs into small interfering RNAs (siRNAs) and modify TE chromatin to
      epigenetically inhibit transcription. Since the populations of small RNAs that
      participate in TE post-transcriptional regulation differ from those that
      establish RNA-directed DNA methylation (RdDM), the mechanism through which
      transcriptionally active TEs transition from post-transcriptional RNAi regulation
      to chromatin level control has remained unclear. We have identified the molecular
      mechanism of a plant pathway that functions to direct DNA methylation to
      transcriptionally active TEs. We demonstrated that 21-22 nucleotide (nt) siRNA
      degradation products from the RNAi of TE mRNAs are directly incorporated into the
      ARGONAUTE 6 (AGO6) protein and direct AGO6 to TE chromatin to guide its function
      in RdDM. We find that this pathway functions in reproductive precursor cells to
      primarily target long centromeric high-copy transcriptionally active TEs for RdDM
      prior to gametogenesis. This study provides a direct mechanism that bridges the
      gap between the post-transcriptional regulation of TEs and the establishment of
      TE epigenetic silencing. 

PMID- 25388953
TI  - Carbon quantum dot-NO photoreleaser nanohybrids for two-photon phototherapy of
      hypoxic tumors.
AB  - We report a conjugate between carbon quantum dots and a NO photoreleaser able to
      photogenerate the anticancer NO radical via an energy transfer mechanism. This
      nanohybrid proved toxic to cancer cells in vitro and significantly reduced tumor
      volume in mice bearing human xenograft BxPC-3 pancreatic tumors upon two-photon
      excitation with the highly biocompatible 800 nm light. 

PMID- 25388954
TI  - Effects of 1-week sacral nerve stimulation on the rectal intestinal epithelial
      barrier and neuromuscular transmission in a porcine model.
AB  - BACKGROUND: Sacral nerve stimulation (SNS) is a validated treatment for fecal
      incontinence, although the mechanism of action remains unknown. Short-term
      effects of SNS on the intestinal epithelial barrier (IEB) have been reported
      previously. The aim of our study was to assess the impact of a 1-week SNS on the
      IEB in a preclinical model. METHODS: Fourteen pigs were implanted for bilateral
      SNS. Seven pigs received 7-day stimulation, whereas the remaining animals
      received no stimulation. Rectal biopsies were performed before and after SNS. We
      assessed IEB permeability, mucosal tight junction and cytokine mRNA expression,
      IL-6 production in an organotypic culture model, and neuromuscular transmission
      in muscle strips. KEY RESULTS: IEB permeability was not modified after
      stimulation, as compared with baseline. The PAR-induced increase in IEB
      permeability and the mucosal ZO-1 mRNA decrease observed in the controls were not
      observed into the stimulated group. Cytokine overexpression was not observed in
      the mucosa in either group. SNS decreased IL-6 production in the organotypic
      culture model. In the stimulated group, the area-under-the-curve of the EFS
      induced contractile response was significantly increased. CONCLUSIONS &
      INFERENCES: The main conclusions of our work are (i) the successful development
      of a preclinical model of bilateral SNS and (ii) in physiological conditions, 1
      week SNS did not lead to functional changes in the mucosa. While under stress
      induced conditions, SNS modified the properties of the IEB, leading to a decrease
      in its permeability. Neuromuscular transmission was modified by SNS, leading to
      neuronal hyperexcitability. These results add evidence to the reinforcement of
      the IEB by SNS.

PMID- 25388955
TI  - Phenotypic identification of subclones in multiple myeloma with different
      chemoresistant, cytogenetic and clonogenic potential.
AB  - Knowledge about clonal diversity and selection is critical to understand multiple
      myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy
      becomes reality, identification and monitoring of intraclonal plasma cell (PC)
      heterogeneity would become increasingly demanded. Here we investigated the
      kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker
      multidimensional flow cytometry (MFC) and principal component analysis, at
      diagnosis and during minimal residual disease (MRD) monitoring. Distinct
      phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients.
      In 10/35 patients, persistent MRD was detected after 9 induction cycles, and
      longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled
      phenotypic clonal tiding after therapy in half (5/10) of the patients. After
      demonstrating selection of distinct phenotypic subsets by therapeutic pressure,
      we investigated whether distinct fluorescence-activated cell-sorted PC subclones
      had different clonogenic and cytogenetic profiles. In half (5/10) of the patients
      analyzed, distinct phenotypic subclones showed different clonogenic potential
      when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic
      subclones displayed unique cytogenetic profiles by interphase fluorescence in
      situ hybridization, including selective del(17p13). Collectively, we unravel
      potential therapeutic selection of preexisting diagnostic phenotypic subclones
      during MRD monitoring; because phenotypically distinct PCs may show different
      clonogenic and cytogenetic profiles, identification and follow-up of unique
      phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.

PMID- 25388956
TI  - Epigenetic aging upon allogeneic transplantation: the hematopoietic niche does
      not affect age-associated DNA methylation.

PMID- 25388958
TI  - Enzymatic synthesis of a DNA triblock copolymer that is composed of natural and
      unnatural nucleotides.
AB  - DNA molecules have come under the spotlight as potential templates for the
      fabrication of nanoscale products, such as molecular-scale electronic or photonic
      devices. Herein, we report an enhanced approach for the synthesis of oligoblock
      copolymer-type DNA by using the Klenow fragment exonuclease minus of E. coli DNA
      polymerase I (KF(-) ) in a multi-step reaction with natural and unnatural
      nucleotides. First, we confirmed the applicability of unnatural nucleotides with
      7-deaza-nucleosides-which was expected because they were non-metalized
      nucleotides-on the unique polymerization process known as the "strand-slippage
      model". Because the length of the DNA sequence could be controlled by tuning the
      reaction time, analogous to a living polymerization reaction on this process,
      stepwise polymerization provided DNA block copolymers with natural and unnatural
      bases. AFM images showed that this DNA block copolymer could be metalized
      sequence-selectively. This approach could expand the utility of DNA as a
      template. 

PMID- 25388957
TI  - Clonal origins of ETV6-RUNX1+ acute lymphoblastic leukemia: studies in
      monozygotic twins.
AB  - Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed
      that ETV6-RUNX1 gene fusion is a common, prenatal genetic event with other driver
      aberrations occurring subclonally and probably postnatally. The fetal cell type
      that is transformed by ETV6-RUNX1 is not identified by such studies or by the
      analysis of early B-cell lineage phenotype of derived progeny. Ongoing, clonal
      immunoglobulin (IG) and cross-lineage T-cell receptor (TCR) gene rearrangements
      are features of B-cell precursor leukemia and commence at the pro-B-cell stage of
      normal B-cell lineage development. We reasoned that shared clonal rearrangements
      of IG or TCR genes by concordant ALL in twins would be informative about the
      fetal cell type in which clonal advantage is elicited by ETV6-RUNX1. Five pairs
      of twins were analyzed for all varieties of IG and TCR gene rearrangements. All
      pairs showed identical incomplete or complete variable-diversity-joining
      junctions coupled with substantial, subclonal and divergent rearrangements. This
      pattern was endorsed by single-cell genetic scrutiny in one twin pair. Our data
      suggest that the pre-leukemic initiating function of ETV6-RUNX1 fusion is
      associated with clonal expansion early in the fetal B-cell lineage. 

PMID- 25388960
TI  - Accuracy of 3D scanners in tooth mark analysis.
AB  - The objective of this study was to compare the accuracy of contact and laser 3D
      scanners in tooth mark analysis. Ten dental casts were scanned with both 3D
      scanners. Seven linear measurements were made from the 3D images of dental casts
      and biting edges generated with DentalPrint(c) software (University of Granada,
      Granada, Spain). The uncertainty value for contact 3D scanning was 0.833 for the
      upper dental cast and 0.660 mm for the lower cast; similar uncertainty values
      were found for 3D-laser scanning. Slightly higher uncertainty values were
      obtained for the 3D biting edges generated. The uncertainty values for single
      measurements ranged from 0.1 to 0.3 mm with the exception of the intercanine
      distance, in which higher values were obtained. Knowledge of the error rate in
      the 3D scanning of dental casts and biting edges is especially relevant to be
      applied in practical forensic cases.

PMID- 25388959
TI  - Biceps femoris and semitendinosus--teammates or competitors? New insights into
      hamstring injury mechanisms in male football players: a muscle functional MRI
      study.
AB  - BACKGROUND: The hamstring injury mechanism was assessed by investigating the
      exercise-related metabolic activity characteristics of the hamstring muscles
      using a muscle functional MRI (mfMRI) protocol. METHODS: 27 healthy male football
      players and 27 football players with a history of hamstring injuries (recovered
      and playing fully) underwent standardised mfMR Imaging. The mfMRI protocol
      consisted of a resting scan, a strenuous bilateral eccentric hamstring exercise
      and a postexercise scan. The exercise-related T2 increase or the signal intensity
      shift between both scans was used to detect differences in metabolic activation
      characteristics (1) between the different hamstring muscle bellies and (2)
      between the injury group and the control group. RESULTS: A more symmetrical
      muscle recruitment pattern corresponding to a less economic hamstring muscle
      activation was demonstrated in the formerly injured group (p<0.05). The injured
      group also demonstrated a significantly lower strength endurance capacity during
      the eccentric hamstring exercise. CONCLUSIONS: These findings suggest that the
      vulnerability of the hamstring muscles to football-related injury is related to
      the complexity and close coherence in the synergistic muscle recruitment of the
      biceps femoris and the semitendinosus. Discrete differences in neuromuscular
      coordination and activity distribution, with the biceps femoris partly having to
      compensate for the lack of endurance capacity of the semitendinosus, probably
      increase the hamstring injury risk.

PMID- 25388961
TI  - Twin reversed arterial perfusion (TRAP) sequence: an acardiac fetus.

PMID- 25388962
TI  - Replication study of previous migraine genome-wide association study findings in
      a Spanish sample of migraine with aura.
AB  - BACKGROUND: Migraine is a common disabling condition that affects approximately
      15% of the population. Several genome-wide association studies have attempted to
      identify susceptibility variants involved in migraine, reporting several
      candidate loci for the disorder. METHODS: In order to replicate findings from
      previous genome-wide association studies, a case-control association study was
      performed. Twelve single nucleotide polymorphisms were genotyped in a Spanish
      sample of 512 migraine with aura patients and 535 migraine-free controls.
      RESULTS: Nominal associations were found for single nucleotide polymorphisms
      rs2651899 (within the PRDM16 gene), rs10166942 (near TRPM8), rs12134493 (close to
      TSPAN2) and rs10504861 (near MMP16) in our migraine with aura sample.
      CONCLUSIONS: Our study provides suggestive replication, in a Spanish migraine
      with aura sample, of four genome-wide association study findings previously
      reported in common migraine. However, larger sample sets should be explored to
      confirm our results.

PMID- 25388963
TI  - Pathogenesis of adult-onset Still's disease: new insights from the juvenile
      counterpart.
AB  - Adult-onset Still's disease (AOSD) is a rare inflammatory disease characterized
      by the classical triad of daily fever, arthritis, and typical salmon-colored
      rash. Recent accumulation of knowledge, mostly arising from hereditary
      autoinflammatory diseases and from the systemic-onset juvenile idiopathic
      arthritis (sJIA), has given raise to new hypotheses on the pathophysiology of
      AOSD. In this review, we first discuss on the continuum between AOSD and sJIA.
      Then, we summarize current hypotheses on the underlying pathogenesis: (1) an
      infectious hypothesis; (2) an autoinflammatory hypothesis; (3) a
      lymphohistiocytic hypothesis; and (4) a hyperferritinemic hypothesis. Finally, we
      present the recent data suggesting that patients with AOSD fall into two distinct
      subgroups with different courses, one with prominent systemic features and one
      with chronic arthritis. 

PMID- 25388964
TI  - sCD163 in AOSD: a biomarker for macrophage activation related to
      hyperferritinemia.
AB  - Ferritin has a key role in Adult-onset Still's disease (AOSD). Its production
      seems related to macrophage activation of which sCD163 is a major serum marker.
      Thus, we aimed at evaluating the role of sCD163 in AOSD and its relationship with
      ferritin. Furthermore, we determined the expression of CD163 and ferritin in a
      lymph-node from an AOSD patient. sCD163 and serum ferritin were measured in 34
      patients with AOSD (21 active, 13 non-active), 18 sepsis and 22 healthy controls
      (HC). Immunohistology was performed on a lymph-node from an AOSD patient in order
      to detect CD163 and ferritin. A tonsil from an HC was used as control. Mean
      sCD163 (8.6 +/- 5.4 mg/L) was higher in active AOSD than "non-active" patients
      (4.6 +/- 2.7 mg/L, p = 0.02). The mean sCD163 in AOSD (6.9 +/- 4.9 mg/L) and
      sepsis (7.1 +/- 5.6 mg/L) were higher than in HC (2.56 +/- 1.17 mg/L, p < 0.001),
      but no difference between AOSD and sepsis was detected. sCD163 positively
      correlated with ferritin (p = 0.0045; r = 0.4755) only in AOSD. Serum ferritin
      (mean 3,640.1 +/- 6,896.9 ug/L) was higher in active AOSD than in sepsis (1,720.2
      +/- 3,882.1 ug/L, p < 0.007). CD163 was equally distributed in the B and T areas
      of both lymph-node and tonsil. Differently from the tonsil, ferritin was
      expressed only in the lymph-node B area. sCD163 is a marker of disease activity
      in AOSD. The correlation with ferritin may lead to hypothesize a macrophage
      activation related to hyperferritinemia. Ferritin was found expressed only in the
      B area of the AOSD lymph-node, suggesting a role for this molecule as an antigen
      in the disease pathogenesis.

PMID- 25388965
TI  - A sudden onset of a pseudo-neurological syndrome after HPV-16/18 AS04-adjuvated
      vaccine: might it be an autoimmune/inflammatory syndrome induced by adjuvants
      (ASIA) presenting as a somatoform disorder?
AB  - In last centuries, vaccines reduced the incidence of several infectious diseases.
      In last decades, some vaccines aimed at preventing also some cancers, where
      viruses play a causative role. However, several adverse events have been
      described after vaccines, but a causal relationship has been established only in
      a minority of cases. Here, we describe a pseudo-neurological syndrome occurred
      shortly after the administration of the bivalent HPV vaccine. Some autoimmune
      disorders, including neurological demyelinating diseases, have been reported
      after HPV vaccines, but the patient showed no organic lesions. The patient was
      diagnosed as having a functional somatoform syndrome, which was supposed to be
      autoimmune/inflammatory syndrome induced by adjuvants (ASIA), seen the temporal
      link with vaccination and the presence of anti-phospholipid autoantibodies.
      Immunological mechanisms of vaccines-and of adjuvants-have not been completely
      elucidated yet, and although there is no evidence of statistical association with
      many post-vaccination events, a causal link with vaccine cannot be excluded in
      some individuals. 

PMID- 25388966
TI  - Paraneoplastic pemphigus associated with primary pulmonar follicular dendritic
      cell sarcoma showing good response to treatment.

PMID- 25388967
TI  - Lichen striatus following influenza infection.

PMID- 25388968
TI  - Development of IRAP- and REMAP-derived SCAR markers for marker-assisted selection
      of the stripe rust resistance gene Yr15 derived from wild emmer wheat.
AB  - KEY MESSAGE: Yr15 provides broad resistance to stripe rust, an important wheat
      disease. REMAP- and IRAP-derived co-dominant SCAR markers were developed and
      localize Yr15 to a 1.2 cM interval. They are reliable across many cultivars.
      Stripe rust [Pucinia striiformis f.sp. tritici (Pst)] is one of the most
      important fungal diseases of wheat, found on all continents and in over 60
      countries. Wild emmer wheat (Triticum dicoccoides), which is the tetraploid
      progenitor of durum wheat, is a valuable source of novel stripe rust resistance
      genes for wheat breeding. T. dicoccoides accession G25 carries Yr15 on chromosome
      1BS. Yr15 confers resistance to virtually all tested Pst isolates; it is
      effective in durum and bread wheat introgressions and their derivatives.
      Retrotransposons generate polymorphic insertions, which can be scored as
      Mendelian markers using techniques such as REMAP and IRAP. Six REMAP- and IRAP
      derived SCAR markers were mapped using 1,256 F2 plants derived from crosses of
      the susceptible T. durum accession D447 (DW1) with its resistant BC3F9 and BC3F10
      (B9 and B10) near isogenic lines, which carried Yr15 introgressed from G25. The
      nearest markers segregated 0.1 cM proximally and 1.1 cM distally to Yr15. These
      markers were also mapped and validated at the same position in another 500
      independent F2 plants derived from crosses of B9 and B10 with the susceptible
      cultivar Langdon (LDN). SC2700 and SC790, defining Yr15 on an interval of 1.2 cM,
      were found to be reliable and robust co-dominant markers in a wide range of wheat
      lines and cultivars with and without Yr15. These markers are useful tags in
      marker-assisted wheat breeding programs that aim to incorporate Yr15 into elite
      wheat lines and cultivars for durable and broad-spectrum resistance to stripe
      rust.

PMID- 25388969
TI  - Assessing the height of block for caesarean section over the past three decades:
      trends from the literature.
AB  - There are multiple methods of assessing the height of block before caesarean
      section under regional anaesthesia, and surveys of practice suggest considerable
      variation in practice. So far, little emphasis has been placed on the guidance to
      be gained from published research literature or textbooks. We therefore set out
      to investigate the methods of block assessment documented in published articles
      and textbooks over the past 30 years. We performed two searches of PubMed for
      randomised clinical trials with caesarean section and either spinal anaesthesia
      or epidural anaesthesia as major Medical Subject Headings. A total of 284 papers,
      from 1984 to 2013, were analysed for methods of assessment of sensory and motor
      block, and the height of block deemed adequate for surgery. We also examined 45
      editions of seven anaesthetic textbooks spanning 1950-2014 for recommended
      methods of assessment and height of block required for caesarean section.
      Analysis of published papers demonstrated a wide variation in techniques, though
      there has been a trend towards the increased use of touch, and an increased use
      of a block height of T5 over the study period. Only 115/284 (40.5%) papers
      described the method of assessing motor block, with most of those that did
      (102/115; 88.7%) describing it as the 'Bromage scale', although only five of
      these (4.9%) matched the original description by Bromage. The required height of
      block recommended by textbooks has risen over the last 30 years to T4, although
      only four textbooks made any recommendation about the preferred sensory modality.
      The variation in methods suggested by surveys of practice is reflected in
      variation in published trials, and there is little consensus or guidance in
      anaesthetic textbooks.

PMID- 25388970
TI  - Connexin 31.1 degradation requires the Clathrin-mediated autophagy in NSCLC cell
      H1299.
AB  - Connexins have relative short half-lives. Connexin 31.1 (Cx31.1) was newly
      reported to be down-regulated in non-small cell lung cancer cell lines, and
      displayed tumour-suppressive properties. However, no reports describing how a
      cell regulates Cx31.1 level were found. In this study, Cx31.1 was suggested to be
      degraded through both ubiquitin-proteasome system (UPS) and autophagy. Blockage
      of UPS with MG-132 increased Cx31.1 level, but could not inhibit the degradation
      of Cx31.1 completely. In H1299 cells stably expressing Cx31.1, Cx31.1 reduced
      when autophagy was induced through starvation or Brefeldin A treatment. Knockdown
      of autophagy-related protein ATG5 could increase the cellular level of Cx31.1
      both under normal growth condition and starvation-induced autophagy.
      Colocalization of Cx31.1 and autophagy marker light chain 3 (LC3) was revealed by
      immunofluorescence analysis. Coimmunoprecipitation and immunofluorescence showed
      that Cx31.1 might interact with clathrin heavy chain which was newly reported to
      regulate autophagic lysosome reformation (ALR) and controls lysosome
      homoeostasis. When clathrin expression was knockdown by siRNA treatment, the
      level of Cx31.1 increased prominently both under normal growth condition and
      starvation-induced autophagy. Under starvation-induced autophagy, LC3-II levels
      were slightly accumulated with siCla. treatment compared to that of siNC, which
      could be ascribed to that clathrin knockdown impaired the late stage of
      autophagy, ALR. Taken together, we found autophagy contributed to Cx31.1
      degradation, and clathrin might be involved in the autophagy of Cx31.1. 

PMID- 25388971
TI  - Insulin-like growth factor 1 can promote proliferation and osteogenic
      differentiation of human dental pulp stem cells via mTOR pathway.
AB  - Insulin-like growth factor 1 (IGF-1) is a multifunctional peptide that can
      enhance osteogenic differentiation of bone marrow mesenchymal stem cells
      (BMMSCs). However, it remains unclear whether IGF-1 can promote osteogenic
      differentiation of human dental pulp stem cells (DPSCs). In our study, DPSCs were
      isolated from the impacted third molars, and treated with IGF-1. Osteogenic
      differentiation abilities were investigated. We found that IGF-1 activated the
      mTOR signaling pathway during osteogenic differentiation of DPSCs. IGF-1 also
      increased the expression of runt-related transcription factor 2 (RUNX2),
      osteocalcin (OCN), osterix (OSX) and collagen type I (COL I) during this process.
      Rapamycin, an mTOR inhibitor, blocked osteogenic differentiation induced by IGF
      1. Meanwhile, CCK-8 assay and flow cytometry results demonstrated that 10-200
      ng/mL IGF-1 could enhance proliferation ability of DPSCs and 100 ng/mL was the
      optimal concentration. In summary, IGF-1 could promote proliferation and
      osteogenic differentiation of DPSCs via mTOR pathways, which might have clinical
      implications for osteoporosis.

PMID- 25388972
TI  - Prevalence of Autism Spectrum Disorder symptoms in children with
      neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition. While
      considerable work has focused on cognitive functioning, several research groups
      also observed difficulties in social functioning as a prominent feature of NF1.
      These problems and the possible link between NF1 and Autism Spectrum Disorder
      (ASD) have become increasingly important in recent NF1 literature. The aim of the
      current study was to assess ASD characteristics in a hospital-based NF1 pediatric
      population (n = 82) using the standardized Children Social Behavior Questionnaire
      (CSBQ) and Social Responsiveness Scale (SRS) to account for the prevalence,
      severity, and nature of social problems. In a parallel study, comprehensive ASD
      assessment was performed in a subgroup of NF1 children with a strong suspicion of
      ASD (n = 31). Results indicate that NF1 children have more social problems than
      typical controls, more frequently reported above 8 years. The SRS shows that 63%
      is at risk of ASD symptoms. According to item analyses, most problems were
      observed on items measuring orientation in, understanding of and being tuned onto
      a social situation (CSBQ) and social cognition and communication (SRS). In the
      parallel study, 27 NF1 children were diagnosed with ASD. These children have a
      distinct phenotype compared to a heterogeneous ASD group, with pronounced social
      communicative impairments and fewer restrictive/repetitive behaviors. This study
      provides a better understanding of social problems in NF1 and the phenotypical
      overlap with ASD symptomatology. Despite their willingness to engage with others,
      NF1 children with or without ASD encounter various difficulties in their social
      communicative life.

PMID- 25388974
TI  - Developing and implementing global gender policy to reduce HIV and AIDS in low-
      and middle-income countries: policy makers' perspectives.
AB  - Gender inequalities have been recognised as central to the HIV epidemic for many
      years. In response, a range of gender policies have been developed in attempts to
      mitigate the impact and transform gender relations. However, the effects of these
      policies have been less than successful. In March 2010 the Joint United Nations
      Programme on HIV/AIDS (UNAIDS) launched the Agenda for accelerated country level
      action on women, girls, gender equality and HIV (the Agenda), an operational plan
      on how to integrate women, girls and gender equality into the HIV response. This
      paper explores the perspectives of those involved in developing and implementing
      the Agenda to understand its strengths and limitations. In-depth one-on-one
      interviews were conducted with 16 individuals involved in the development and
      implementation of the Agenda. The data were analysed using thematic network
      analysis. Facilitators of the Agenda centred on the Agenda's ability to create
      political space for women and girls within the global HIV/AIDS response and the
      collaborative process of developing the Agenda. Barriers to the implementation
      and development of the Agenda include the limited financial and non-financial
      resources, the top-down nature of the Agenda's development and implementation and
      a lack of political will from within UNAIDS to implement it. We suggest that the
      Agenda achieved many goals, but its effect was constrained by a wide range of
      factors. 

PMID- 25388975
TI  - Most at-risk populations: contextualising HIV prevention programmes targeting
      marginalised groups in Zanzibar, Tanzania.
AB  - According to a 2009 UNAIDS report the HIV/AIDS prevalence rate in Zanzibar,
      Tanzania, is low in the general population (0.6%), but high among vulnerable
      groups, specifically sex workers (10.8%), injecting drug users (15.1%), and men
      who have sex with men (12.3%). In response to this concentrated epidemic, the
      Government of Zanzibar, international and local non-profit organisations have
      focused their prevention activities on these marginal populations. Although these
      efforts are beneficial in terms of disseminating information about HIV/AIDS and
      referring clients to health clinics, they fail to address how the socio-economic
      status of these groups places them at a greater risk for contracting and dying
      from the virus. Furthermore, there is an absence of qualitative research on these
      populations which is needed to understand the challenges these groups face and to
      improve the effectiveness of interventions. Through interviews with employees of
      government agencies and non-profit organisations, medical professionals,
      vulnerable populations and HIV/AIDS patients, this paper used a political economy
      of health and syndemic framework to examine how local realities inform and
      challenge HIV/AIDS programmes in Zanzibar. 

PMID- 25388973
TI  - Opportunity costs of reward delays and the discounting of hypothetical money and
      cigarettes.
AB  - Humans are reported to discount delayed rewards at lower rates than nonhumans.
      However, nonhumans are studied in tasks that restrict reinforcement during
      delays, whereas humans are typically studied in tasks that do not restrict
      reinforcement during delays. In nonhuman tasks, the opportunity cost of
      restricted reinforcement during delays may increase delay discounting rates. The
      present within-subjects study used online crowdsourcing (Amazon Mechanical Turk,
      or MTurk) to assess the discounting of hypothetical delayed money (and cigarettes
      in smokers) under four hypothetical framing conditions differing in the
      availability of reinforcement during delays. At one extreme, participants were
      free to leave their computer without returning, and engage in any behavior during
      reward delays (modeling typical human tasks). At the opposite extreme,
      participants were required to stay at their computer and engage in little other
      behavior during reward delays (modeling typical nonhuman tasks). Discounting
      rates increased as an orderly function of opportunity cost. Results also
      indicated predominantly hyperbolic discounting, the "magnitude effect," steeper
      discounting of cigarettes than money, and positive correlations between
      discounting rates of these commodities. This is the first study to test the
      effects of opportunity costs on discounting, and suggests that procedural
      differences may partially account for observed species differences in
      discounting. 

PMID- 25388976
TI  - HIV-serostatus disclosure in the context of free antiretroviral therapy and socio
      economic dependency: experiences among women living with HIV in Tanzania.
AB  - The worldwide implementation of free antiretroviral therapy (ART) raised great
      hopes among policy makers and health organisations about the positive changes it
      would bring about in attitudes and behaviours towards HIV and AIDS, as well as
      for infected people's lives. A change in illness perception was anticipated,
      leading to the hypothesis of a possible change in disclosure rates, patterns and
      the choice of significant others to inform. In the era of free treatment
      availability in the United Republic of Tanzania, we examined reasons for
      disclosure and non-disclosure among HIV-seropositive women enrolled on ART and
      their choice of significant others to inform. In so doing, we contribute to the
      necessary yet neglected debate about the social impact of ART on the lives of
      infected women. The study, for which an ethnographic cross-sectional pilot
      approach was chosen, was conducted at the Care and Treatment Center (CTC) at
      Bombo Regional Hospital (BRH) in Tanga city, Tanzania. Data presented here derive
      from participant observation, questionnaires and semi-structured interviews
      conducted with 59 HIV-seropositive women on ART. Interestingly, and despite
      treatment availability, the choice of significant others to inform, as well as
      reasons for disclosure and non-disclosure, mirror findings from previous studies
      conducted before the introduction of free ART. The main reason for non-disclosure
      was fear of discrimination. The hope for social, economic or health support was
      the main motivation for disclosure, followed by the need for a 'clinic companion'
      in order to receive ART, as requested by hospital staff. Nevertheless, healthcare
      staff were not unanimous in thinking that disclosure is always beneficial, thus
      the recommended extent of disclosure varied. ART and concomitant factors were
      raised as an entirely new and significant reason for disclosure by interviewees.
      Finally, findings confirm that despite ART, disclosure remains a highly stressful
      event for women. 

PMID- 25388977
TI  - Tangible skill building and HIV youth prevention intervention in rural South
      Africa.
AB  - There have been countless youth programmes throughout Africa resulting in
      increased knowledge of HIV, but all too often there is a discrepancy between
      knowledge and behaviour change. According to available literature, successful
      projects need to consider the context in which young people live, be consistent
      with community values, and be family inclusive and youth centred. This, however,
      requires active involvement of communities, families and youth, which in turn
      implies a more local response to the epidemic in small projects. This paper
      presents results from a survey in a rural community of South Africa which
      investigated the contextual factors associated with HIV knowledge, attitudes and
      practice in such a setting. The community was of particular interest as it had
      developed a local youth literacy and family support programme which included HIV
      prevention messages. All school aged children of the two settlements were
      approached (N = 100), some of whom regularly participated in the literacy
      classes. The survey investigated the association between contextual factors such
      as caregivers, peers and exposure to the literacy classes in regards to HIV
      knowledge, attitudes and practice. The results suggest that contextual factors
      have an impact on sexual behaviour and self-efficacy as well as on attitudes
      towards condom use. This indicates that peers and caregivers influence the
      perceived agency to practise safe sex and the likelihood that adolescents
      practise 'deviant' behaviour such as drinking, getting involved in drugs or
      becoming sexually active. However, the results suggest that exposure to community
      projects such as literacy classes have the potential to positively influence
      reading scores, attitudes towards condom use and delay of sexual debut while it
      has little effect on HIV knowledge. 

PMID- 25388978
TI  - Obstacles to HIV prevention, treatment and care in selected public universities
      in South Africa.
AB  - South Africa, like the rest of Southern Africa, is ravaged by AIDS. Higher
      education in South Africa has a significant role to play in the fight against the
      spread of HIV and AIDS. This article reports the factors contributing to the
      spread of HIV and AIDS in three selected public universities in South Africa. To
      achieve the stated aim, the study answered the following research question: What
      are the factors contributing to the spread of HIV and AIDS in South African
      public universities? The problem in this study stems from South Africa's HIV and
      AIDS infection rate, one of the highest in the world, especially in KwaZulu
      Natal. A qualitative approach was adopted by conducting focus group interviews
      with the students. The data were analysed using axial coding and open coding,
      where dominant themes from the discussions were identified and discussed in
      detail. The findings show that barriers to HIV and AIDS prevention, care and
      treatment exist in the tertiary institutions under study. Social and economic
      interventions are needed to stem the spread of HIV and AIDS at tertiary
      institutions. A range of recommendations for halting the spread of HIV and AIDS
      in these institutions is provided. 

PMID- 25388980
TI  - The HIV/AIDS caregiver identity as a double-edged sword: a discourse analysis on
      HIV/AIDS caregiving in South Africa.
AB  - This article discusses the identity of HIV/AIDS caregivers as constructed by a
      group of HIV/AIDS caregivers at a non-profit organisation in South Africa. During
      a 12-month period data were collected through interviews with the organisation's
      staff and volunteers. Using discourse analysis, the study identified a caregiver
      identity constructed by participants. This caregiving identity acts as a double
      edged sword: while the rewards of caregiving act as a buffer against stressful
      experiences, the prescriptive nature of the caregiver identity is taxing, and may
      explain burnout among HIV/AIDS caregivers. The study concludes that for support
      systems for HIV/AIDS caregivers to be effective, the social culture and identity
      of HIV/AIDS caregivers must be considered. 

PMID- 25388979
TI  - Institutionalisation of knowledge transfer on sexual behaviour in the times of
      AIDS: a case study from a village community in north-central Namibia.
AB  - This paper concentrates on the changes in knowledge transfer in northern Namibia
      with respect to sexual norms, behavioural advice and sexual health information.
      The research was conducted in a small village community in Ohangwena region,
      where over 100 semi-structured and structured interviews were held with a sample
      of 67 community members and 50 professionals dealing with HIV/AIDS issues. The
      results of the research indicate the change in social roles in family and
      community dynamics, especially between generations, and thus a change in trust,
      respect and responsibility attached to information sharing. This further exerts
      pressure on the classification, choice, adaptation and transmission of
      information at both the individual and family level. Secondly, and partly as a
      consequence of this, the levels of indigenous, community level information from
      elders to youth and the level of institutionalised information sharing leave
      space for variations in behavioural norms. The research contributes to the
      discussion on problems in information sharing, knowledge transfer and adaptation
      of behavioural advice in HIV/ AIDS work. 

PMID- 25388981
TI  - Socio-economic and demographic factors related to HIV status in urban informal
      settlements in the Eastern Cape, South Africa.
AB  - The prevalence of HIV&AIDS is embedded in social and economic inequity and the
      relationship between social determinants and HIV incidence is well established.
      The aim of this study was to determine which socio-economic and demographic
      factors are related to HIV status in the age group 18 to 49 years in informal
      settlements in the Eastern Cape, South Africa. This cross-sectional study was
      conducted in 3 informal settlements (n = 752) during March 2013 within the Nelson
      Mandela Bay and Buffalo City districts. A proportional cluster sample was
      selected and stratified by area and formal plot/squatter households in open
      areas. Respondents who volunteered to participate had to provide informed written
      consent before trained, bilingual peer educators interviewed them and completed
      the structured questionnaire. HIV status was determined and information on
      demographic and socio-economic variables was included in the bivariate analysis.
      The prevalence of HIV was higher, at 17.3%, than the 2011 estimated national
      prevalence among the general population in South Africa. The level of education
      (chi(2) = 5.50, df = 1, p < 0.05), geographical site (chi(2) = 7.41, df = 2, p <
      0.05), gender (chi(2) = 33.10, df = 1, p < 0.0005), household food insecurity
      (chi(2) = 4.77, df = 1, p < 0.05), cooking with cast iron pots (chi(2) = 15.0, df
      = 3, p < 0.05) and availability of perceived 'wealth' indicators like mobile
      telephones and refrigerators (chi(2) = 9.67, df = 2, p < 0.05) were significantly
      associated with HIV-status. No significant associations could be demonstrated
      between household income, the number of people living in the household and the
      availability of electricity/water and HIV status. As the observed levels of HIV
      prevalence underlined gender bias and failure to graduate from high school,
      future interventions should focus on HIV prevention in female schoolchildren.
      However, HIV infection is also prevalent among wealthier individuals in informal
      settlements, which indicates that renewed efforts should be made to improve
      sexual risk behaviour within this group. 

PMID- 25388982
TI  - Reasons for the low uptake of adult male circumcision for the prevention of HIV
      transmission in Swaziland.
AB  - Swaziland is currently experiencing the worst impact of HIV and AIDS of any
      country in the world. In an effort to curb further spread of the virus, the
      country adopted mass male circumcision (MC) as recommended by the World Health
      Organization in 2007. Despite intense campaigns to promote the procedure over the
      past three years, the uptake of circumcision remains very low for reasons that
      are not very clear. The purpose of this study was to explore the reasons for the
      low uptake of MC in Swaziland despite the massive national MC campaigns. A
      qualitative research design was used, in which all men who were targeted by the
      mass MC campaign were eligible. Participants were identified as they came for
      sexual and reproductive health services at the Family Life Association of
      Swaziland (FLAS) Clinic, Mbabane. In-depth, individual face-to-face unstructured
      interviews were conducted to elicit the reasons why men were not going for
      circumcision. A total of 17 men were interviewed. Results showed that these
      reasons include fear of the procedure and the possible outcome, perception of no
      significant benefit of the procedure, impatience about waiting for the procedure
      or the healing process, religious/cultural beliefs, and worries about the fate of
      the foreskin. These reasons were attributed to misconceptions and lack of
      accurate and specific information about some aspects of the circumcision strategy
      of HIV preventions. Physiological changes and economic activities associated with
      adulthood were also found to be hindrances to MC uptake. The study recommended
      that a comprehensive description of the procedure and more precise facts and
      scientific bases of the MC strategy be incorporated and emphasised in the MC
      campaigns. Involvement of religious leaders will also facilitate clarification of
      religious or cultural misunderstandings or misconceptions. A focus on neonatal MC
      would also help. 

PMID- 25388983
TI  - Drivers for the effective management of HIV and AIDS in the South African
      construction industry--a Delphi study.
AB  - Different industries manage the threats presented by HIV and AIDS in different
      ways. The construction industry is particularly vulnerable to the pandemic
      because of its large unskilled labour force, high labour turnover and the
      migratory nature of the workforce. The study reported on in this paper, the first
      of its kind in the South African construction industry, aimed to identify the
      important drivers needed for the effective management of HIV and AIDS and to
      understand their impact on the construction industry. The aim was achieved in two
      stages. The first stage involved an extensive literature review to determine the
      factors that drive corporate response in the management of HIV and AIDS in the
      South African construction sector. Six drivers, namely legal requirements, social
      pressures, business costs, voluntary regulation, visibility of the disease, and
      individuals within companies with a total of 87 items were identified. An
      iterative Delphi technique with a panel of experts was used to validate the
      factors identified in the literature review and formed the second stage of this
      research. The Delphi method was used as it provided a systematic approach to
      achieve consensus on the six drivers for effective management of HIV and AIDS
      management in the construction industry. An expert panel responded to three
      iterations of questionnaires to achieve consensus. The experts reached consensus
      on 56 items categorised under the 6 drivers. This study found that the legal
      driver was considered most important but only second in terms of impact. The
      second most important driver was the visibility of the disease and was regarded
      as the driver with the highest impact. Internal agents ranked third in terms of
      importance and impact. This study can be used for further research to assist the
      construction industry in helping fight HIV and AIDS. 

PMID- 25388984
TI  - Reproductive behaviour among women on antiretroviral therapy in Botswana:
      mismatched pregnancy plans and contraceptive use.
AB  - Understanding pregnancy planning and contraceptive use is important in preventing
      unplanned/unwanted pregnancies among women on antiretroviral therapy (ART).
      Through a cross-sectional survey of 155 women living with HIV on ART in Botswana
      (mean age = 36), bivariate/multivariate analyses were used to identify and
      understand pregnancy planning and contraceptive use. Women who did not plan to
      have a child (n = 85) were older, less educated, had more children and worried
      about stigmatisation from family and healthcare workers (HCWs). Multivariate
      analyses found age (OR:3.41; CI:1.57-7.45; p = 0.002); perceived stigmatisation
      from family and healthcare workers (OR:3.62; CI:1.47-8.96; p = 0.005); and
      believing it is irresponsible for women living with HIV to want a child (OR:2.40;
      CI:1.10-5.24; p = 0.028) to be significantly associated with not planning to have
      a child. Although reported condom use among 85 women who did not plan to have a
      child was nearly 90%, a total of 26 of these women (34%) believed they did not
      have control over condom use. Lack of contraception was reported by 6 women who
      did not plan a child; this, coupled with the lack of control over condom use,
      puts unmet need for contraception at 38%. Most women reported feeling comfortable
      talking with HCWs about contraceptives. However, almost a quarter of the women
      indicated they were infrequently advised about contraceptives at ART clinics.
      This study found discordance between pregnancy planning and contraceptive use
      among women on ART. Lack of control over condom use coupled with low hormonal
      contraceptive use creates unmet need for contraception and increases the risk of
      unwanted pregnancies. Regular clinic visits for women on ART present excellent
      opportunities to address contraceptive needs in a considerate and comprehensive
      manner. 

PMID- 25388985
TI  - Restricted disease propagation in multiple system atrophy with prolonged
      survival.

PMID- 25388987
TI  - Characterization of low molecular weight allergens from English walnut (Juglans
      regia).
AB  - Although English walnut is a commonly allergenic tree nut, walnut allergens have
      been poorly characterized to date. The objective of this work was to characterize
      the natural, low molecular weight (LMW) allergens from walnut. A protocol was
      developed to purify LMW allergens (specifically 2S albumins) from English
      walnuts. In addition to 2S albumins, a series of peptides from the N-terminal
      region of the 7S seed storage globulin proprotein were also identified and
      characterized. These peptides comprised a four-cysteine motif (C-X-X-X-C-X10-12-C
      X-X-X-C) repeated throughout the 7S N-terminal region. Upon IgE immunoblotting,
      3/11 and 5/11 sera from walnut-allergic subjects showed IgE reactivity to the 7S
      N-terminal fragments and 2S albumin, respectively. The mature 7S protein and the
      newly described 7S N-terminal peptides represent two distinct types of allergens.
      Because the proteolytic processing of 7S globulins has not been elucidated in
      many edible plant species, similar protein fragments may be present in other nuts
      and seeds. 

PMID- 25388986
TI  - A population pharmacokinetic model of valproic acid in pediatric patients with
      epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation.
AB  - BACKGROUND AND OBJECTIVE: Valproic acid (VPA) follows a non-linear
      pharmacokinetic profile in terms of protein-binding saturation. The total daily
      dose regarding VPA clearance is a simple power function, which may partially
      explain the non-linearity of the pharmacokinetic profile; however, it may be
      confounded by the therapeutic drug monitoring effect. The aim of this study was
      to develop a population pharmacokinetic model for VPA based on protein-binding
      saturation in pediatric patients with epilepsy. METHODS: A total of 1,107 VPA
      serum trough concentrations at steady state were collected from 902 epileptic
      pediatric patients aged from 3 weeks to 14 years at three hospitals. The
      population pharmacokinetic model was developed using NONMEM((r)) software. The
      ability of three candidate models (the simple power exponent model, the dose
      dependent maximum effect [DDE] model, and the protein-binding model) to describe
      the non-linear pharmacokinetic profile of VPA was investigated, and potential
      covariates were screened using a stepwise approach. Bootstrap, normalized
      prediction distribution errors and external evaluations from two independent
      studies were performed to determine the stability and predictive performance of
      the candidate models. RESULTS: The age-dependent exponent model described the
      effects of body weight and age on the clearance well. Co-medication with
      carbamazepine was identified as a significant covariate. The DDE model best
      fitted the aim of this study, although there were no obvious differences in the
      predictive performances. The condition number was less than 500, and the
      precision of the parameter estimates was less than 30 %, indicating stability and
      validity of the final model. CONCLUSION: The DDE model successfully described the
      non-linear pharmacokinetics of VPA. Furthermore, the proposed population
      pharmacokinetic model of VPA can be used to design rational dosage regimens to
      achieve desirable serum concentrations.

PMID- 25388988
TI  - Expression analysis of genes encoding mitogen-activated protein kinases in maize
      provides a key link between abiotic stress signaling and plant reproduction.
AB  - Mitogen-activated protein kinases (MAPKs) play important roles in stress
      responses and development in plants. Maize (Zea mays), an important cereal crop,
      is a model plant species for molecular studies. In the last decade, several MAPKs
      have been identified in maize; however, their functions have not been studied
      extensively. Genome-wide identification and expression analysis of maize MAPK
      genes could provide valuable information for understanding their functions. In
      this study, 20 non-redundant maize MAPK genes (ZmMPKs) were identified via a
      genome-wide survey. Phylogenetic analysis of MAPKs from maize, rice (Oryza
      sativa), Arabidopsis (Arabidopsis thaliana), poplar (Populus trichocarpa), and
      tomato (Solanum lycopersicum) classified them into four major classes. ZmMPKs in
      the same class had similar domains, motifs, and genomic structures. Gene
      duplication investigations suggested that segmental duplications made a large
      contribution to the expansion of ZmMPKs. A number of cis-acting elements related
      to plant development and response to stress and hormones were identified in the
      promoter regions of ZmMPKs. Furthermore, transcript profile analysis in eight
      tissues and organs at various developmental stages demonstrated that most ZmMPKs
      were preferentially expressed in reproductive tissues and organs. The transcript
      abundance of most ZmMPKs changed significantly under salt, drought, cold, or
      abscisic acid (ABA) treatments, implying that they might participate in abiotic
      stress and ABA signaling. These expression analyses indicated that ZmMPKs might
      serve as linkers between abiotic stress signaling and plant reproduction. Our
      data will deepen our understanding of the complexity of the maize MAPK gene
      family and provide new clues to investigate their functions. 

PMID- 25388990
TI  - Melatonin attenuates neutrophil inflammation and mucus secretion in cigarette
      smoke-induced chronic obstructive pulmonary diseases via the suppression of Erk
      Sp1 signaling.
AB  - The incidence of chronic obstructive pulmonary disease (COPD) has substantially
      increased in recent decade. Cigarette smoke (CS) is the most important risk
      factor in the development of COPD. In this study, we investigated the effects of
      melatonin on the development of COPD using a CS and lipopolysaccharide (LPS)
      induced COPD model and cigarette smoke condensate (CSC)-stimulated NCI-H292
      cells, a human mucoepidermoid carcinoma cell. On day 4, the mice were treated
      intranasally with LPS. The mice were exposed to CS for 1 hr per day (8 cigarettes
      per day) from day 1 to day 7. Melatonin (10 or 20 mg/kg) was injected
      intraperitoneally 1 hr before CS exposure. Melatonin markedly decreased the
      neutrophil count in the BALF, with reduction in the proinflammatory mediators and
      MUC5AC. Melatonin inhibited Erk phosphorylation and Sp1 expression induced by CS
      and LPS treatment. Additionally, melatonin decreased airway inflammation with a
      reduction in myeloperoxidase expression in lung tissue. In in vitro experiments,
      melatonin suppressed the elevated expression of proinflammatory mediators induced
      by CSC treatment. Melatonin reduced Erk phosphorylation and Sp1 expression in CSC
      stimulated H292 cells. In addition, cotreatment of melatonin and Erk inhibitors
      significantly limited the proinflammatory mediators with greater reductions in
      Erk phosphorylation and Sp1 expression than that observed in H292 cells treated
      with Erk inhibitor alone. Taken together, melatonin effectively inhibited the
      neutrophil airway inflammation induced by CS and LPS treatment, which was closely
      related to downregulation of Erk phosphorylation. These findings suggest that
      melatonin has a therapeutic potential for the treatment of COPD.

PMID- 25388989
TI  - Periodontal innate immune mechanisms relevant to atherosclerosis.
AB  - Atherosclerosis is a common cardiovascular disease in the USA where it is a
      leading cause of illness and death. Atherosclerosis is the most common cause for
      heart attack and stroke. Most commonly, people develop atherosclerosis as a
      result of diabetes, genetic risk factors, high blood pressure, a high-fat diet,
      obesity, high blood cholesterol levels, and smoking. However, a sizable number of
      patients suffering from atherosclerosis do not harbor the classical risk factors.
      Ongoing infections have been suggested to play a role in this process.
      Periodontal disease is perhaps the most common chronic infection in adults with a
      wide range of clinical variability and severity. Research in the past decade has
      shed substantial light on both the initiating infectious agents and host
      immunological responses in periodontal disease. Up to 46% of the general
      population harbors the microorganism(s) associated with periodontal disease,
      although many are able to limit the progression of periodontal disease or even
      clear the organism(s) if infected. In the last decade, several epidemiological
      studies have found an association between periodontal infection and
      atherosclerosis. This review focuses on exploring the molecular consequences of
      infection by pathogens that exacerbate atherosclerosis, with the focus on
      infections by the periodontal bacterium Porphyromonas gingivalis as a running
      example. 

PMID- 25388991
TI  - Role of percutaneous transcatheter embolization (PTE) in the treatment of
      spontaneous bleeding associated with anticoagulant therapy.
AB  - PURPOSE: To evaluate safety and clinical efficacy of percutaneous transcatheter
      embolization (PTE) in the treatment of spontaneous bleedings (SBs) in patients
      submitted to chronic anticoagulation therapy. MATERIALS AND METHODS: From January
      2007 to December 2012, 20 patients (mean age 75.8 years, range 68-91 years) with
      23 SBs were retrospectively evaluated. Active bleeding was documented by contrast
      enhanced-multidetector row computed tomography (CE-MDCT). PTE was performed using
      different embolic agents. Technical success (TS), clinical success (CS), late
      success (LS) and mortality rate (M) related to the angiographic procedure and
      complications were evaluated. RESULTS: CE-MDCT and digital subtraction
      angiography (DSA) identified active bleeding sites in 18 cases (18/20). In two
      cases (2/20) DSA did not confirm the arterial bleeding diagnosed on CE-MDCT.
      Twenty-three sessions of PTE were performed. TS, CS, LS and M were, respectively,
      100, 85, 15 and 0%. No major complications were observed. CONCLUSIONS: PTE could
      be considered a safe and effective "first line" approach to treat SB associated
      with anticoagulation therapy.

PMID- 25388992
TI  - Relaxin-2 expression in temporal bone carcinoma.
AB  - Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive
      malignancy with a significant local recurrence rate even in patients with
      postoperative pathology reports of free surgical margins. This raises the
      question of how "free" negative margins should be to be oncologically safe,
      especially in bone tissue. A potential role for relaxin-2 hormone in tumor-driven
      osteolysis has recently been reported. The aim of this study was to assess the
      prognostic role of relaxin-2 expression in TBSCC tissue specimens and
      pathologically negative bone margins. Relaxin-2 immunohistochemical expression
      was assessed in 25 consecutively operated TBSCC patients. Several pathological
      variables correlated with recurrence rate (pT stage, dura mater involvement),
      disease-free survival (DFS) (pT stage, pN status, grade, and dura mater
      involvement), and disease-specific survival (DSS) (pT stage, pN status, grade,
      and dura mater involvement). The recurrence rate, DFS, and DSS did not correlate
      with relaxin-2 expression in TBSCC specimens or pathologically negative bone
      margins. Although local recurrence in TBSCC could relate to neoplastic bone
      invasion not apparent on conventional pathological investigations, the present
      preliminary findings seem to rule out any role of relaxin-2 in mediating this
      local aggressiveness. Molecular mechanisms of TBSCC recurrence after curative
      treatment should be further investigated. 

PMID- 25388993
TI  - Long-term results of combined approach in parotid sialolithiasis.
AB  - Combined sialendoscopic and transcutaneous approach in parotid sialolithiasis is
      a surgical option for large and impacted stones. The aim of this study is to
      assess the long-term results regarding postoperative stenosis, recurrent
      swellings and gland function. Prospective study in a tertiary referral center of
      patients with parotid sialolithiasis requiring combined approach. A total of 12
      patients have been treated within a period of 3 years. Intraductal stents were
      placed in 9 of 12 cases. Scintigraphic evaluation of salivary glands and follow
      up sialendoscopy performed 1 year postoperatively. In total, fourteen stones (two
      stones in two cases) were successfully removed along with two coexisted
      inflammatory polyps. Postoperative endoscopic evaluation revealed mild stenosis
      in 7 out of 12 cases without clinical significance as no recurrent swellings were
      reported. Scintigraphy showed normal gland function in 11 cases and mild
      hypofunction in 1 case with long-standing history of sialolithiasis. All patients
      were free of symptoms within the follow-up period of time (median follow-up 15.5
      months). Combined approach is a safe, gland preserving and efficacious procedure
      in long term. The stenosis in the area of ductal surgical opening when present
      does not seem to be of clinical value.

PMID- 25388994
TI  - Boronate cross-linked ATP- and pH-responsive nanogels for intracellular delivery
      of anticancer drugs.
AB  - A novel adenosine-5'-triphosphate (ATP) and pH dual-responsive degradable nanogel
      (NG) system are developed based on the complexation of 1,2-diols in dendritic
      polyglycerol (dPG), and boronic acids, which are conjugated with dPG as the
      macromolecular cross-linker. The NG is formed by a mild and surfactant-free
      inverse nanoprecipitation method. An anticancer drug, methotrexate (MTX), is
      coprecipitated with the macromolecular precursors and cross-linkers to form MTX
      loaded NG (NG-MTX) with a loading capacity of 13 wt%. The size of NG is
      controllable from 100 to 300 nm, which is suitable for the enhanced permeation
      and retention (EPR) effect and can be degraded into small fragments that are
      within the clearance limitation in the presence of 5 * 10(-3) m ATP or at pH 4
      after 24 h. Increasing ATP concentrations and decreasing pH values of the release
      medium accelerate the release of MTX. Both the real-time cell analysis (RTCA) and
      MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) results show
      no cytotoxic effect of NG and a dose-dependent effect of NG-MTX on HeLa cells as
      well as MCF-7 cells. The fluorescein isothiocyanate (FITC)-labeled NG (FITC-NG)
      exhibits a time-dependent intracellular uptake tendency and cell organelle
      permeability as determined by confocal laser scanning microscopy (CLSM) or flow
      cytometry. 

PMID- 25388995
TI  - Utilization of postanastomotic side branches for the assessment of anastomotic
      patency.

PMID- 25388996
TI  - Muscle versus fasciocutaneous free flaps in heel reconstruction: systematic
      review and meta-analysis discussion.

PMID- 25388997
TI  - Case report of a supraclavicular artery island flap for reconstruction of a
      nonhealing cervical spine wound.

PMID- 25388998
TI  - Pectoralis major myocutaneous flap versus free fasciocutaneous flap for
      reconstruction of partial hypopharyngeal defects: what should we be doing?
AB  - BACKGROUND: Partial hypopharyngeal defects are most commonly reconstructed with
      the pectoralis major myocutaneous flap (PMMF) or free fasciocutaneous (FFC) flap.
      The purpose of this study is to determine the ideal method for reconstruction of
      partial hypopharyngeal defects by reviewing our institutional experience and the
      literature. METHODS: A retrospective review of partial hypopharyngeal
      reconstructions since 2009 was performed. A National Library of Medicine search
      of studies on partial hypopharyngeal reconstruction since 1988 was performed.
      Data on complications, diet, and speech were extracted and pooled. RESULTS: A
      total of 18 patients were studied-9 had PMMF reconstruction and 9 had FFC
      reconstruction. Operative time (8.75 vs. 13.0 hours, p = 0.0003) was shorter in
      the PMMF group. Pharyngocutaneous fistula developed in one PMMF patient (11.1%)
      and two FFC patients (22.2%). Late strictures occurred in three PMMF patients.
      Six patients in each group (66.7%) progressed to a regular diet. Three patients
      in each group produced tracheoesophageal speech after TEP. Literature review
      identified 36 relevant studies, with 301 patients reconstructed with PMMF and 605
      patients with FFC. Pooled-data analysis revealed that PMMF had higher reported
      rates of fistula (24.7 vs. 8.9%, p < 0.0001) and requirement for second surgery
      (11.3 vs. 5.5%, p = 0.04). There was no difference in stricture rates or
      progression to regular diet. Fewer PMMF patients produced tracheoesophageal
      speech (17.5 vs. 52.1%, p < 0.0001). CONCLUSIONS: PMMF and FFC flaps are valid
      approaches to reconstructing partial hypopharyngeal defects, though rates in the
      literature of fistula, need for revisional surgery, and tracheoesophageal speech
      after laryngectomy are more favorable after free flap reconstruction.

PMID- 25388999
TI  - Quantitative evaluation of blood perfusion to nerves included in the
      anterolateral thigh flap using indocyanine green fluorescence angiography: a
      different contrast pattern between the vastus lateralis motor nerve and femoral
      cutaneous nerve.
AB  - BACKGROUND: Better postoperative results can be expected in nerve reconstruction
      when vascularized nerve grafts are used. Previous studies reported reconstruction
      with flaps including "vascularized" nerves; however, few have evaluated blood
      supply to these nerves. The aim of this study was to quantitatively assess blood
      perfusion to nerves included in anterolateral thigh (ALT) flaps by indocyanine
      green (ICG) fluorescence angiography. PATIENTS AND METHODS: Participants
      comprised eight patients who underwent reconstructive surgery with nerve defects
      using free ALT flaps, including the vastus lateralis motor nerve and/or femoral
      cutaneous nerve. Intraoperative ICG fluorescent angiography was performed. Time
      after the drug injection and the intensity of fluorescence in these nerves were
      analyzed as time-intensity curves. Maximum intensity (Imax), time to Imax (Tmax),
      and time at the beginning of intensity elevation (Te) were measured at three
      points: Point C, the central portion of the flap-attached region of the nerve;
      Point P, 2 cm from the proximal flap-attached edge; and Point D, 2 cm from the
      distal edge. RESULTS: Imax and Te at point C and Imax/Tmax-Te at point P were
      significantly different between these two nerves (p = 0.03125, p = 0.02895, p =
      0.03125, respectively). Fluorescence in the vastus lateralis motor nerve was
      slightly quicker and stronger than that in the femoral cutaneous nerve, and also
      exhibited an axial pattern of fluorescence. CONCLUSION: Intraoperative ICG
      fluorescent angiography can be used to determine which nerve is better for nerve
      reconstruction. The indexes of Imax, Te, and Imax/Tmax-Te may be the suitable
      criteria for decision making regarding donor nerve selection.

PMID- 25389000
TI  - Response to letter to the editor, "BET inhibitor JQ1 blocks inflammation and bone
      destruction".

PMID- 25389001
TI  - Letter to the Editor, "BET inhibitor JQ1 blocks inflammation and bone
      destruction".

PMID- 25389002
TI  - TLR2 promoter hypermethylation creates innate immune dysbiosis.
AB  - Periodontitis is a common chronic inflammatory disease that is initiated by a
      complex microbial biofilm that poses significant health and financial burdens
      globally. Porphyromonas gingivalis is a predominant pathogen that maintains
      chronic inflammatory periodontitis. Toll-like receptors (TLRs) play an important
      role in periodontitis by recognizing pathogens and maintaining tissue
      homeostasis. Deficiencies in TLR expression and downstream signaling may reduce
      the host's innate defenses against pathogens, leading to bacterial persistence
      and exacerbated inflammation, which are now being better appreciated in disease
      pathologies. In the case of periodontitis, gingival epithelial cells form the
      first line of defense against pathogens. Innate immune dysregulation in these
      cells relates to severe disease pathology. We recently identified a blunted TLR2
      expression in certain gingival epithelial cells expressing diminished cytokine
      signaling upon P. gingivalis stimulation. Upon detailed analysis of the TLR2
      promoter CpG Island, we noted higher CpG methylation in this dysregulated cell
      type. When these cells were treated with DNA methyltransferase inhibitor, TLR2
      mRNA and cytokine expression were significantly increased. If TLR2 expression
      plasmid was ectopically expressed in dysfunctional cells prior to P. gingivalis
      stimulation, the cytokine expression was increased, confirming the requirement of
      TLR2 in the P. gingivalis-mediated inflammatory response. We designed a chronic
      in vitro infection model to test if P. gingivalis can induce DNA methylation in
      normal gingival epithelial cells that express higher TLR2 upon agonist
      stimulation. Chronic treatment of normal epithelial cells with P. gingivalis
      introduced de novo DNA methylation within the cells. In addition, increased DNA
      methylation was observed in the gingiva of mice infected with P. gingivalis in a
      periodontitis oral gavage model. Moreover, tissues obtained from periodontitis
      patients also exhibited differential TLR2 promoter methylation, as revealed by
      bisulfite DNA sequencing. Taken together, DNA methylation of TLR2 can modulate
      host innate defense mechanisms that may confer increased disease susceptibility. 

PMID- 25389003
TI  - Proresolving nanomedicines activate bone regeneration in periodontitis.
AB  - Therapies to reverse tissue damage from osteolytic inflammatory diseases are
      limited by the inability of current tissue-engineering procedures to restore lost
      hard and soft tissues. There is a critical need for new therapeutics in
      regeneration. In addition to scaffolds, cells, and soluble mediators necessary
      for tissue engineering, control of endogenous inflammation is an absolute
      requirement for success. Although significant progress has been made in
      understanding natural resolution of inflammation pathways to limit uncontrolled
      inflammation in disease, harnessing the biomimetic properties of proresolving
      lipid mediators has not been demonstrated. Here, we report the use of nano
      proresolving medicines (NPRM) containing a novel lipoxin analog (benzo-lipoxin
      A4, bLXA4) to promote regeneration of hard and soft tissues irreversibly lost to
      periodontitis in the Hanford miniature pig. In this proof-of-principle
      experiment, NPRM-bLXA4 dramatically reduced inflammatory cell infiltrate into
      chronic periodontal disease sites treated surgically and dramatically increased
      new bone formation and regeneration of the periodontal organ. These findings
      indicate that NPRM-bLXA4 is a mimetic of endogenous resolving mechanisms with
      potent bioactions that offers a new therapeutic tissue-engineering approach for
      the treatment of chronic osteolytic inflammatory diseases. 

PMID- 25389004
TI  - The molecular basis of hereditary enamel defects in humans.
AB  - The formation of human enamel is highly regulated at the molecular level and
      involves thousands of genes. Requisites for development of this highly
      mineralized tissue include cell differentiation; production of a unique
      extracellular matrix; processing of the extracellular matrix; altering of cell
      function during different stages of enamel formation; cell movement and
      attachment; regulation of ion and protein movement; and regulation of hydration,
      pH, and other conditions of the microenvironment, to name just a few. Not
      surprising, there is a plethora of hereditary conditions with an enamel
      phenotype. The objective of this review was to identify the hereditary conditions
      listed on Online Mendelian Inheritance in Man (OMIM) that have an associated
      enamel phenotype and whether a causative gene has been identified. The OMIM
      database was searched with the terms amelogenesis, enamel, dental, and tooth, and
      all results were screened by 2 individuals to determine if an enamel phenotype
      was identified. Gene and gene product function was reviewed on OMIM and from
      publications identified in PubMed. The search strategy revealed 91 conditions
      listed in OMIM as having an enamel phenotype, and of those, 71 have a known
      molecular etiology or linked genetic loci. The purported protein function of
      those conditions with a known genetic basis included enzymes, regulatory
      proteins, extracellular matrix proteins, transcription factors, and transmembrane
      proteins. The most common enamel phenotype was a deficient amount of enamel, or
      enamel hypoplasia, with hypomineralization defects being reported less
      frequently. Knowing these molecular defects allows an initial cataloging of
      molecular pathways that lead to hereditary enamel defects in humans. This
      knowledge provides insight into the diverse molecular pathways involved in enamel
      formation and can be useful when searching for the genetic etiology of hereditary
      conditions that involve enamel. 

PMID- 25389005
TI  - Green-solvent-processed molecular solar cells.
AB  - High-efficiency bulk heterojunction (BHJ) organic solar cells with power
      conversion efficiencies of more than 5 % can be fabricated using the green
      solvent 2-MeTHF. The active layers comprise a blend of a molecular semiconductor
      donor with intermediate dimensions (X2) and the soluble fullerene derivative
      [6,6]-phenyl-C61 -butyricacidoctylester (PC61 BC8 ). A switch of the processing
      solvent from chloroform to 2-MeTHF leads to no negative impacts on the morphology
      and charge-transport properties of optimally performing BHJ films. Examinations
      by absorption spectroscopy, atomic force microscopy, and grazing incidence wide
      angle X-ray scattering reveal no significant modification of morphology. These
      results show that green solvents can be excellent alternatives for large-area
      printing of high-performance organic photovoltaics (OPVs) and thus open new
      opportunities for sustainable mass production of organic solar cells and other
      optoelectronic devices. 

PMID- 25389006
TI  - Mesenchymal stem cells alleviate atherosclerosis by elevating number and function
      of CD4(+)CD25 (+)FOXP3 (+) regulatory T-cells and inhibiting macrophage foam cell
      formation.
AB  - Atherosclerosis is a chronic inflammatory disease characterized by the formation
      of plaques inside arteries, leading to narrowing and blockage. Potential
      therapeutic strategies include expanding the population of regulatory T-cells
      (Tregs) to enhance atheroprotective immunity, and inhibiting the formation of
      macrophage foam cells. Here, we studied the effect of bone marrow-derived
      mesenchymal stem cells (BM-MSCs) on atherosclerotic plaque formation in
      Apolipoprotein E(-/-) (ApoE-KO) mice, and elucidated the underlying mechanism. BM
      MSCs isolated from 4 week-old ApoE-KO mice were evaluated by flow cytometry for
      expression of MSC-specific markers. Thirty eight week-old ApoE-KO mice were
      randomly divided into three experimental groups (n = 10 per group): 1. MSC group
      received BM-MSCs intravenously; 2. Vehicle group-received DMEM; 3. Control group
      did not receive any treatment. Administration of MSCs resulted in a marked
      decrease in the size of atherosclerotic plaques 3 months after treatment. In
      addition, the number and function of CD4(+)CD25(+)FOXP3(+) regulatory T-cells
      (Tregs) in cultured splenocytes, and the expression of FOXP3 at both mRNA and
      protein levels, was significantly increased in the MSC group. In vitro
      experiments further indicated that the formation of macrophage foam cells was
      inhibited by treatment with MSCs, accompanied by a significant downregulation in
      CD36 and scavenger receptor A (SRA). Our findings suggest that MSCs play an
      atheroprotective role by enhancing the number and function of Tregs and
      inhibiting the formation of macrophage foam cells. Hence, administration of MSCs
      to atherosclerotic patients might have significant clinical benefits.

PMID- 25389007
TI  - Is chronic obstructive pulmonary disease a risk factor for epistaxis after
      coronary artery bypass graft surgery?
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has customarily been
      associated with increased surgical morbidity and mortality rates after coronary
      artery bypass graft surgery (CABG). The aim of this study was to determine
      whether there is a relationship between epistaxis and COPD after CABG surgery.
      METHODS: There were 3 443 patients who consecutively underwent isolated CABG from
      January 2002 to March 2012. We retrospectively analysed the data of 27 patients
      (0.8%) with newly developed and serious spontaneous epistaxis, which required
      consultation with the Ear Nose and Throat (ENT) Department. The patients were
      divided into three groups according to severity of nasal bleeding. Twenty-one
      (77.7%) patients in the three groups had COPD. RESULTS: There were 19 males (70%)
      and eight females (30%). Their ages ranged between 52 and 72 years (mean 61 +/-
      5). Fifty-five per cent of the patients had hypertension and 78% had COPD. The
      overall duration of hospital stay was six to 11 days (mean 7.9 +/- 1.1).
      Epistaxis was seen particularly on the fourth and seventh days postoperatively
      and 17 patients (63%) were treated with anterior, posterior, or anterior and
      posterior nasal packing (group 1). Nasal bleeding was controlled with
      electrocautery in six patients (22%) (group 2), and four (15%) were treated with
      surgical excision and blood transfusions (group 3). All patients (100%) had a
      good recovery with no mortality. CONCLUSION: The high coincidence between
      epistaxis and COPD made us wonder whether COPD may be a risk factor for epistaxis
      after CABG surgery. However, we could not find any direct causative link between
      COPD and epistaxis in patients who had undergone CABG. Epistaxis was more common
      in patients with COPD and it was more serious clinically in patients who had both
      COPD and hypertension.

PMID- 25389012
TI  - Impact of the Mental Health Nurse Incentive Programme on patient functioning.
AB  - The Mental Health Nurse Incentive Programme (MHNIP) was established across
      Australia during 2007. The programme enables mental health nurses to work
      alongside general practitioners (GPs) and other health professionals to assist in
      the assessment and treatment of people with mental illnesses. This paper reports
      on the outcomes for 309 patients referred by GPs to the programme in one region
      of Queensland. Standardized measures were completed pre- and post-treatment to
      evaluate changes in symptoms and general functioning between baseline and follow
      up. Patient contact with the programme ranged from 3 weeks to 38 weeks, and the
      study group (n = 84) demonstrated significant improvement on all of the self
      report and clinician-rated measures employed. Effect sizes ranged from 0.59 to
      0.74. The findings suggest that the MHNIP is making a positive contribution, with
      a medium-to-large impact on the mental health and general functioning of
      individuals supported through the programme. Further evaluation work is required
      to determine if the findings from this study can be generalized more broadly. 

PMID- 25389013
TI  - Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F
      FDG imaging of myocardial inflammation in mice.
AB  - PURPOSE: Myocardial inflammation is an emerging target for novel therapies and
      thus for molecular imaging. Positron emission tomography (PET) with (18)F
      fluorodeoxyglucose (FDG) has been employed, but requires an approach for
      suppression of cardiomyocyte uptake. We tested clinically viable strategies for
      their suitability in mouse models in order to optimize preclinical imaging
      protocols. METHODS: C57BL/6 mice (n = 56) underwent FDG PET under various
      conditions. In healthy animals, the effect of low-dose (5 units/kg) or high-dose
      (500 units/kg, 15 min prior) intravenous heparin, extended fasting (18 h) and the
      impact of conscious injection with limited, late application of isoflurane
      anaesthesia after 40 min of conscious uptake were examined in comparison to
      ketamine/xylazine anaesthesia. Conscious injection/uptake strategies were further
      evaluated at 3 days after permanent coronary artery occlusion. RESULTS: Under
      continuous isoflurane anaesthesia, neither heparin administration nor extended
      fasting significantly impacted myocardial (18)F-FDG accumulation. Injection with
      40 min uptake in awake mice resulted in a marked reduction of global myocardial
      (18)F-FDG uptake compared to standard isoflurane anaesthesia (5.7 +/- 1.1 %ID/g
      vs 30.2 +/- 7.9 %ID/g, p < 0.01). Addition of heparin and fasting further reduced
      uptake compared to conscious injection alone (3.8 +/- 1.5 %ID/g, p < 0.01)
      similar to ketamine/xylazine (2.4 +/- 2.2 %ID/g, p < 0.001). In the inflammatory
      phase, 3 days after myocardial infarction, conscious injection/uptake with and
      without heparin/fasting identified a marked increase in myocardial (18)F-FDG
      accumulation that was similar to that observed under ketamine/xylazine.
      CONCLUSION: Continuous isoflurane anaesthesia obscures any suppressive effect of
      heparin or fasting on cardiomyocyte glucose utilization. Conscious injection of
      FDG in rodents significantly reduces cardiomyocyte uptake and enables further
      suppression by heparin and fasting, similar to clinical observations. In contrast
      to ketamine/xylazine, this represents a more physiological, translatable strategy
      for suppression of cardiomyocyte (18)F-FDG uptake when targeting myocardial
      inflammation.

PMID- 25389014
TI  - Characterization of an N-glycosylated Bacillus subtilis leucine aminopeptidase
      expressed in Pichia pastoris.
AB  - Aminopeptidase is an important flavorsome especially in protein hydrolysate
      debittering by removing hydrophobic amino acid residue at the N-terminal end.
      Besides, it is also applied to preparation of active peptides and analysis of
      protein sequence. In this study, leucine aminopeptidase from Bacillus subtilis
      was cloned and expressed in Pichia pastoris, a widely used heterologous protein
      expression host. Then it was purified and characterized. After methanol induction
      for 96 h, the aminopeptidase activity in culture supernatant reached 28.4 U
      ml(A1) , which was 7.1 times that of wild strain B. subtilis Zj016. The optimal
      temperature and pH of the purified recombinant enzyme were 60  degrees C and 8.5,
      respectively. The purified aminopeptidase was stable within 30-60  degrees C and
      pH 8.0-9.0. It was intensively inhibited by Ni(2beta) , Ca(2beta) , DL
      dithiothreitol (DTT) and ethylene diamine tetraacetic acid (EDTA), but activated
      by Co(2beta) . The Km toward leucine-p-nitroanilines (Leu-pNA) of the enzyme was
      0.97 mM. The sequence analysis of aminopeptidase indicated three potential N
      glycosylation sites and it was further verified via MALDI-TOF-MS analysis.
      Consequently, the N-glycosylated aminopeptidase exhibited higher thermostability
      and catalytic efficiency. The purified enzyme exhibited two bands through sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) while a single band
      can be identified when the enzyme was deglycosylated. Circular dichroism
      spectroscopy indicated that the secondary structure of recombinant aminopeptidase
      was similar to the wild-type.

PMID- 25389015
TI  - Perceptions of postnatal depression and health care needs in a South African
      sample: the "mental" in maternal health care.
AB  - BACKGROUND: Maternal mental health care is a neglected area in low and middle
      income countries (LAMIC) such as South Africa, where maternal and child health
      care priorities are focused on reducing maternal and infant mortality and
      promoting infant physical health. In the context of a paucity of mental health
      specialists, the aim of this study was to understand the explanatory models of
      illness held by women with maternal depression with the view to informing the
      development of an appropriate counselling intervention using a task sharing
      approach. METHODS: Twenty semi-structured qualitative interviews were conducted
      with mothers from a poor socio-economic area who were diagnosed with depression
      at the time of attending a primary health care facility. Follow-up interviews
      were conducted with 10 participants in their homes. RESULTS: Dimensions of
      poverty, particularly food and financial insecurity and insecure accommodation;
      unwanted pregnancy; and interpersonal conflict, particularly partner rejection,
      infidelity and general lack of support were reported as the causes of depression.
      Exacerbating factors included negative thoughts and social isolation. Respondents
      embraced the notion of task sharing, indicating that counselling provided by
      general health care providers either individually or in groups could be helpful.
      CONCLUSION: Counselling interventions drawing on techniques from cognitive
      behavioural therapy and problem solving therapy within a task sharing approach
      are recommended to build self-efficacy to address their material conditions and
      relationship problems in poorly resourced primary health care facilities in South
      Africa.

PMID- 25389017
TI  - Plant lignin content altered by soil microbial community.
AB  - Questions have been raised in various fields of research about the consequences
      of plants with modified lignin production. As a result of their roles in nutrient
      cycling and plant diversity, plant-soil interactions should be a major focus of
      ecological studies on lignin-modified plants. However, most studies have been
      decomposition studies conducted in a single soil or in sterile soil. Thus, we
      understand little about plant-soil interactions in living lignin-modified plants.
      In lignin mutants of three different barley (Hordeum vulgare) cultivars and their
      corresponding wild-types associated with three different soil microbial
      communities, we asked: do plant-soil microbiome interactions influence the lignin
      content of plants?; does a mutation in lignin production alter the outcome of
      plant-soil microbiome interactions?; does the outcome of plant-soil microbiome
      interactions depend on host genotype or the presence of a mutation altering
      lignin production? In roots, the soil community explained 6% of the variation in
      lignin content, but, in shoots, the soil community explained 21% of the variation
      in lignin content and was the only factor influencing lignin content. Neither
      genotype nor mutations in lignin production explained associations with fungi.
      Lignin content changes in response to a plant's soil microbial community, and may
      be a defensive response to particular components of the soil community. 

PMID- 25389018
TI  - Low cord blood vitamin D levels are associated with increased milk sensitization
      in early childhood.
AB  - BACKGROUND: The association between vitamin D status at birth and allergen
      sensitizations is uncertain. The aim of this study was to investigate the
      relationship between cord blood vitamin D status with allergen sensitizations and
      the development of atopic diseases in early childhood. METHODS: Children aged 0
      through 4 yr from a birth cohort in the Prediction of Allergies in Taiwanese
      Children (PATCH) study were enrolled. Serum levels of 25-hydroxyvitamin D
      (25(OH)D) in cord blood were measured by a new automated electrochemiluminescence
      based assay. Specific IgE antibodies against food and inhalant allergens were
      measured at 6 months, and 1, 1.5, 2, 3, and 4 yr of age. RESULTS: A total of 186
      children were regular followed up at clinics for a 4-yr follow-up period. The
      mean level of cord blood 25(OH)D was 23.8 +/- 9.5 ng/ml with a high prevalence of
      low vitamin D status (<20 ng/ml) at birth (42%). There was a tendency of low cord
      blood 25(OH)D levels being associated with higher risk of food sensitization
      throughout childhood. Cord blood 25(OH)D levels were inversely associated with
      the risk of milk sensitization at age 2, at which age a higher prevalence of milk
      sensitization was significantly associated with the risk of allergic rhinitis,
      and asthma development at age 4. CONCLUSIONS: Low cord blood vitamin D levels
      appear to be associated with increased milk sensitization but not with asthma,
      eczema, or allergic rhinitis in early childhood.

PMID- 25389019
TI  - The recognition and management of intrapartum fetal heart rate emergencies:
      beyond definitions and classification.
AB  - The ongoing and well-documented debate about the value of electronic fetal
      monitoring has focused primarily on the fact that most variant fetal heart rate
      (FHR) patterns are poor predictors of fetal acid-base status. Most recently, much
      of this attention has been focused on the implications for clinical management of
      FHR patterns that the National Institute of Child Health and Human Development
      has classified as indeterminate: neither normal nor abnormal. Given that a
      majority of fetuses will have an FHR pattern considered indeterminate at some
      point in labor, this is an important and worthwhile discussion. It is also
      important, however, for providers to be able to recognize those patterns that
      signal the presence of developing acidemia and those that signal the potential
      presence of an acute obstetric complication that can quickly lead to acidemia and
      fetal asphyxia, such as a placental abruption or uterine rupture. Early
      identification of these FHR patterns, and immediate intervention to improve
      oxygenation or expedite birth, may help improve neonatal outcomes. The first part
      of this article presents descriptions of theses FHR patterns. The route and
      timing of birth during these emergencies is then discussed. The last part of the
      article presents an overview of strategies for optimizing the efficiency of
      providers, particularly teams of providers, in responding to FHR emergencies. The
      use of simulation-based training is reviewed, with specific focus on its
      potential application in the context of preparing for these emergencies. 

PMID- 25389020
TI  - The activity concentration of post-Chernobyl 137Cs in the area of the Opole
      Anomaly (southern Poland).
AB  - During the years 2007 and 2010, the activity concentration of (137)Cs accumulated
      in soil, mosses Pleurozium schreberi and lichens Hypogymnia physodes was
      measured. The studies covered the areas of the so-called Opole Anomaly. In
      consequence of the Chernobyl nuclear power plant breakdown in 1986, relatively
      large amounts of this radionuclide were deposited in this area. In some areas of
      the Anomaly, over 100 times higher surface activity of (137)Cs was detected,
      compared to the lowest values registered in Poland. Currently, (137)Cs is still
      present in woodlands and wastelands. As at 2 April 2013, the surface activity
      concentration of (137)Cs in soil on the tested area was from 0.34 to 67.5 kBq m(
      2). In comparison, the surface activity concentration of (137)Cs as at 1 June
      1986, soon after deposition, was from 2.08 to over 125 kBq m(-2). The maximum
      specific activity concentrations of (137)Cs in mosses and lichens sampled for
      testing in 2010 were respectively 1234 and 959 Bq kg(-1). It was also proven that
      the changes in activity concentration of (137)Cs in the area of the Anomaly are
      mainly the consequence of the radioactive decay of this radionuclide. 

PMID- 25389016
TI  - ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity.
AB  - BACKGROUND: The role of innate immunity in general and of type I interferon (IFN
      I) in particular in HTLV-1 pathogenesis is still a matter of debate. ADAR1-p150
      is an Interferon Stimulated Gene (ISG) induced by IFN-I that can edit viral RNAs.
      We therefore investigated whether it could play the role of an anti-HTLV factor.
      RESULTS: We demonstrate here that ADAR1 is also expressed in the absence of IFN
      stimulation in activated primary T-lymphocytes that are the natural target of
      this virus and in HTLV-1 or HTLV-2 chronically infected T-cells. ADAR1 expression
      is also increased in primary lymphocytes obtained from HTLV-1 infected
      individuals. We show that ADAR1 enhances HTLV-1 and HTLV-2 infection in T
      lymphocytes and that this proviral effect is independent from its editing
      activity. ADAR1 expression suppresses IFN-alpha inhibitory effect on HTLV-1 and
      HTLV-2 and acts through the repression of PKR phosphorylation. DISCUSSION: This
      study demonstrates that two interferon stimulated genes, i.e. PKR and ADAR1 have
      opposite effects on HTLV replication in vivo. The balanced expression of those
      proteins could determine the fate of the viral cycle in the course of infection.

PMID- 25389021
TI  - Numerical assessment of nutrient assimilative capacity of Khur-e-Musa in the
      Persian Gulf.
AB  - Khur-e-Musa is a predominantly tide-driven marine creek located in the
      northwestern part of the Persian Gulf. The port city of Mahshahr and several
      important industrial enterprises are located in the vicinity of this marine
      creek. Therefore, marine pollution due to discharge from regional industries into
      this water body has been a matter of interest for environmental studies. In this
      paper, nutrient assimilative capacity of the Khur-e-Musa during the summer time
      was studied. In order to perform any engineering project or marine environment
      study related to Khur-e-Musa, the prediction of currents is an essential task.
      Therefore, MIKE 3-FM hydrodynamic and quality model was used to simulate
      nutrients and chlorophyll a concentrations. OECD open boundary index was used to
      determine the trophic status probabilities. Different scenarios were defined and
      simulated to find the minimum nutrient load that causes eutrophication in all
      parts of Khur-e-Musa simultaneously. The results showed assimilative capacity of
      7,180 kg/day TN and 1,305 kg/day TP for Khur-e-Musa. 

PMID- 25389022
TI  - Comparison of arsenic uptake ability of barnyard grass and rice species for
      arsenic phytoremediation.
AB  - In this research, the relative performance in arsenic (As) remediation was
      evaluated among some barnyard grass and rice species under hydroponic conditions.
      To this end, four barnyard grass varieties and two rice species were selected and
      tested for their remediation potential of arsenic. The plants were grown for 2
      weeks in As-rich solutions up to 10 mg As L(-1) to measure their tolerance to As
      and their uptake capabilities. Among the varieties of plants tested in all
      treatment types, BR-29 rice absorbed the highest amount of As in the root, while
      Nipponbare translocated the maximum amount of As in the shoot. Himetainubie
      barnyard grass produced the highest biomass, irrespective of the quantity of As
      in the solution. In all As-treated solutions, the maximum uptake of As was found
      in BR-29 followed by Choto shama and Himetainubie. In contrast, while the
      bioaccumulation factor was found to be the highest in Nipponbare followed by BR
      29 and Himetainubie. The results suggest that both Choto shama and Himetainubie
      barnyard grass varieties should exhibit a great potential for As removal, while
      BR-29 and Nipponbare rice species are the best option for arsenic
      phytoremediation. 

PMID- 25389023
TI  - Prevalence of multidrug-resistant, coagulase-positive Staphylococcus aureus in
      nasal carriage, food, wastewater and paper currency in Jalandhar city (north
      western), an Indian state of Punjab.
AB  - Development of multidrug-resistant pattern in the bacterial community is a major
      threat to the society. Staphylococcus aureus is perhaps the pathogen of the
      greatest concern because of its inherent virulence, its ability to cause a
      diverse array of life-threatening situations and capacity to adapt to different
      environmental conditions. The aims of this study is to investigate the multidrug
      resistant pattern of the coagulase-positive S. aureus isolated from nasal
      carriage, food, paper currency and wastewater samples. We had also studied the
      multiple antibiotic resistance index and in vitro production of beta-lactamase.
      The study had found out 130 coagulase-positive S. aureus strains isolated from
      total of 595 samples such as anterior nares of preschool children (195), hospital
      nurses (100), drivers (76), food (86), wastewater (3) and paper currency (135)
      (Indian rupee). The biotypes pattern were as follows; A > D > B > C> UT. Multiple
      antibiotic resistance (MAR) value clearly defines the multidrug-resistant pattern
      of the S. aureus among different sources. Statistical analysis (one-way ANOVA) of
      results obtained indicated that the difference in the antibiotic resistance
      observed in the 130 bacterial isolates against the 23 different antibiotics used
      in this study was statically significant (p < 0.01). 

PMID- 25389024
TI  - Antipodal cells persist through fertilization in the female gametophyte of
      Arabidopsis.
AB  - The female gametophyte of most flowering plants forms four cell types after
      cellularization, namely synergid cell, egg cell, central cell and antipodal cell.
      Of these, only the antipodal cells have no established functions, and it has been
      proposed that in many plants including Arabidopsis, the antipodal cells undergo
      programmed cell death during embryo sac maturation and prior to fertilization.
      Here, we examined the expression of female gametophyte-specific fluorescent
      reporters in mature embryo sacs of Arabidopsis, and in developing seeds shortly
      after fertilization. We observed expression of the fluorescence from the reporter
      genes in the three antipodal cells in the mature stage embryo sac, and continuing
      through the early syncytial endosperm stages. These observations suggest that
      rather than undergoing programmed cell death and degenerating at the mature stage
      of female gametophyte as previously supposed, the antipodal cells in Arabidopsis
      persist beyond fertilization, even when the other cell types are no longer
      present. The results support the concept that the Arabidopsis female gametophyte
      at maturity should be considered to be composed of seven cells and four cell
      types, rather than the previously prevailing view of four cells and three cell
      types.

PMID- 25389025
TI  - Step-by-step clinical management of one-lung ventilation: continuing professional
      development.
AB  - PURPOSE: The purpose of this Continuing Professional Development Module is to
      review the issues pertinent to one-lung ventilation (OLV) and to propose a
      management strategy for ventilation before, during, and after lung isolation.
      PRINCIPAL FINDINGS: The need for optimal lung isolation has increased with the
      advent of video-assisted thoracoscopic surgery, as surgical exposure is critical
      for successful surgery. Continuous positive airway pressure applied to the
      operative lung or intermittent two-lung ventilation should therefore be avoided
      if possible. Optimal management of OLV should provide adequate oxygenation and
      also prevent acute lung injury (ALI), the leading cause of death following lung
      resection. Research conducted in the last decade suggests implementing a
      protective ventilation strategy during OLV that consists of small tidal volumes
      based on ideal body weight, routine use of positive end-expiratory pressure, low
      inspired oxygen fraction, with low peak and plateau airway pressures. High
      respiratory rates to compensate for low tidal volumes may predispose to
      significant air trapping during OLV, so permissive hypercapnea is routinely
      employed. The management of OLV extends into the period of two-lung ventilation,
      as the period prior to OLV impacts lung collapse, and both the time before and
      after OLV influence the extent of ALI. Lung re-expansion at the conclusion of OLV
      is an important component of ensuring adequate ventilation and oxygenation
      postoperatively but may be harmful to the lung. CONCLUSIONS: Optimal
      perioperative care of the thoracic patient includes a protective ventilation
      strategy from intubation to extubation and into the immediate postoperative
      period. Anesthetic goals include the prevention of perioperative hypoxemia and
      postoperative ALI.

PMID- 25389026
TI  - Anatomical variations of the internal iliac veins in the presacral area: Clinical
      implications during sacral colpopepxy or extended pelvic lymphadenectomy.
AB  - The purpose of this study was to classify anatomical variations of the internal
      iliac vein (IIV) in relation to robotic or laparoscopic extended lymphadenectomy.
      Between March 2011 and July 2012, 60 consecutive patients underwent robotic or
      laparoscopic extended lymphadenectomy. We retrospectively reviewed surgical video
      clips and analyzed the pattern of the IIVs in the presacral area. IIV variations
      were classified into seven types: Type A, normal (n = 39, 65.0%); Type A with a
      dilated middle sacral vein (n = 5, 8.3%); Type B, left IIV connecting centrally
      to the left external iliac vein (n = 5, 8.3%); Type C, a separated trunk of the
      left IIV draining into the left central common iliac vein (CIV; n = 1, 1.7%);
      Type D, a separated trunk of the right IIV draining into the left central CIV (n
      = 8, 13.3%); Type E, a separated trunk of the right IIV draining into the right
      central CIV (n = 0, 0%); and Type F, separated trunks of the bilateral IIV
      connecting with each other before draining into the left central CIV (n = 2,
      3.3%). The prevalence of IIV anomalies was 26.7%; the incidence of separated IIV
      trunks was 18.3%. To prevent life-threatening IIV injury during extended
      lymphadenectomy or sacral colpopexy, the anatomical variations of the IIVs should
      be known exactly.

PMID- 25389028
TI  - Cardiovascular risk factors and cardiac disorders in long-term survivors of
      pediatric liver transplantation.
AB  - The MetS and cardiovascular disease are leading causes of late morbidity in adult
      liver transplantation recipients; however, limited data are available in
      pediatric liver transplantation. A single-center retrospective review was
      undertaken for patients who had a liver transplantation before 18 yr of age and
      were >5 yr post-transplantation, to study the prevalence of MetS, its components,
      and cardiac disorders. Fifty-eight patients were included in the study with a
      mean age at transplantation of 6.3 +/- 6.1 yr and mean follow-up of 14.1 +/- 6.0
      yr. Of the study group, 41.4% were overweight or obese, with ongoing prednisone
      use and increased duration of follow-up being significant risk factors. Fifty
      three patients had sufficient data for determining MetS, which was present in 17%
      of the patients. Although the prevalence of MetS is low in pediatric liver
      transplant recipients, it is associated with CKD and prednisone therapy (p <
      0.05). Echocardiography data were available for 23 patients, of whom 43.4% had
      LVH and 13% had evidence of PH. The spectrum of cardiac disorders in this
      population is much wider than in adults. 

PMID- 25389027
TI  - High-intensity cannabis use associated with lower plasma human immunodeficiency
      virus-1 RNA viral load among recently infected people who use injection drugs.
AB  - INTRODUCTION AND AIMS: Cannabis use is common among people who are living with
      human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS).
      While there is growing pre-clinical evidence of the immunomodulatory and anti
      viral effects of cannabinoids, their possible effects on HIV disease parameters
      in humans are largely unknown. Thus, we sought to investigate the possible
      effects of cannabis use on plasma HIV-1 RNA viral loads (pVLs) among recently
      seroconverted illicit drug users. DESIGN AND METHODS: We used data from two
      linked longitudinal observational cohorts of people who use injection drugs.
      Using multivariable linear mixed-effects modelling, we analysed the relationship
      between pVL and high-intensity cannabis use among participants who seroconverted
      following recruitment. RESULTS: Between May 1996 and March 2012, 88 individuals
      seroconverted after recruitment and were included in these analyses. Median pVL
      in the first 365 days among all seroconverters was 4.66 log10 c mL(-1) . In a
      multivariable model, at least daily cannabis use was associated with 0.51 log10 c
      mL(-1) lower pVL (beta = -0.51, standard error = 0.170, P value = 0.003).
      DISCUSSION AND CONCLUSIONS: Consistent with the findings from recent in vitro and
      in vivo studies, including one conducted among lentiviral-infected primates, we
      observed a strong association between cannabis use and lower pVL following
      seroconversion among illicit drug-using participants. Our findings support the
      further investigation of the immunomodulatory or antiviral effects of
      cannabinoids among individuals living with HIV/AIDS.

PMID- 25389029
TI  - Hypoglossal nerve stimulation in the treatment of obstructive sleep apnea: A
      systematic review and meta-analysis.
AB  - OBJECTIVES/HYPOTHESIS: Poor adherence to continuous positive airway pressure
      treatment in obstructive sleep apnea (OSA) adversely affects the effectiveness of
      this therapy. This study aimed to systematically review the evidence regarding
      the efficacy and safety of hypoglossal nerve stimulation as an alternative
      therapy in the treatment of OSA. DATA SOURCES: Scopus, PubMed, and Cochrane
      Library databases were searched (updated through September 5, 2014). METHODS:
      Studies were included that evaluated the efficacy of hypoglossal nerve
      stimulation to treat OSA in adults with outcomes for apnea-hypopnea index (AHI),
      oxygen desaturation index (ODI), and effect on daytime sleepiness (Epworth
      Sleepiness Scale [ESS]). Tests for heterogeneity and subgroup analysis were
      performed. RESULTS: Six prospective studies with 200 patients were included in
      this review. At 12 months, the pooled fixed effects analysis demonstrated
      statistically significant reductions in AHI, ODI, and ESS mean difference of 
      17.51 (95% CI: -20.69 to -14.34); -13.73 (95% CI: -16.87 to -10.58), and -4.42
      (95% CI: -5.39 to -3.44), respectively. Similar significant reductions were
      observed at 3 and 6 months. Overall, the AHI was reduced between 50% and 57%, and
      the ODI was reduced between 48% and 52%. Despite using different hypoglossal
      nerve stimulators in each subgroup analysis, no significant heterogeneity was
      found in any of the comparisons, suggesting equivalent efficacy regardless of the
      system in use. CONCLUSIONS: This review reveals that hypoglossal nerve
      stimulation therapy may be considered in selected patients with OSA who fail
      medical treatment. Further studies comparing hypoglossal nerve stimulation with
      conventional therapies are needed to definitively evaluate outcomes. LEVEL OF
      EVIDENCE: NA

PMID- 25389030
TI  - Multicentre analysis of long-term outcome after surgical resection for gastric
      cancer liver metastases.
AB  - BACKGROUND: The efficacy of surgical resection for gastric cancer liver
      metastases (GCLMs) is currently debated. Hitherto, no large-scale clinical
      studies have been conducted. METHODS: This retrospective multicentre study
      analysed a database of consecutive patients with either synchronous or
      metachronous metastases who underwent surgical R0 resection for GCLM between 1990
      and 2010. Clinical data were collected from five cancer centres in Japan.
      Survival curves were assessed, and clinical parameters were evaluated to identify
      predictors of prognosis. RESULTS: A total of 256 patients were enrolled. The
      mean(s.d.) number of hepatic tumours resected was 2.0(2.4). The surgical
      mortality rate was 1.6 per cent. Median follow-up was 65 (range 1-261) months.
      Recurrences were detected in 192 patients (75.0 per cent). The median interval
      from hepatic resection to recurrence was 7 (range 1-72) months, and the dominant
      site of recurrence was the liver (72.4 per cent). Actuarial 1-, 3- and 5-year
      overall and recurrence-free survival rates were 77.3, 41.9 and 31.1 per cent, and
      43.6, 32.4 and 30.1 per cent, respectively. Median overall and recurrence-free
      survival times were 31.1 and 9.4 months respectively. Multivariable analysis
      identified serosal invasion of the primary gastric cancer (hazard ratio (HR)
      1.50; P = 0.012), three or more liver metastases (HR 2.33; P < 0.001) and liver
      tumour diameter at least 5 cm (HR 1.62; P = 0.005) as independent predictors of
      poor survival. CONCLUSION: Clinically resectable GCLM is rare, but strict and
      careful patient selection can lead to long-term survival following R0 surgical
      resection.

PMID- 25389031
TI  - Parkinson's disease incidence and prevalence assessment in France using the
      national healthcare insurance database.
AB  - BACKGROUND AND PURPOSE: The incidence and prevalence of Parkinson's disease are
      important for public health planning yet there is a lack of representative, up-to
      date estimations for France. METHODS: For this cross-sectional study, subjects
      with suspected Parkinson's were identified in the EGB database, a 1/97 random
      sample of the national healthcare insurance database, linked to the national
      hospital-discharge summary database. Incidence and prevalence were estimated
      using a specific definition that included those with a diagnosis (hospitalization
      or listed as a long-term chronic disease for full reimbursement) and a sensitive
      definition that also included those with an indicative drug reimbursement
      profile. Estimations were extrapolated to the national population, standardizing
      on age and gender. RESULTS: According to either the specific or the sensitive
      definitions, the annual incidence of Parkinson's disease during the study period
      was respectively 36 and 49 per 100,000 person-years and prevalence in 2010 was
      308-410 per 100,000 persons in the population as a whole. According to the age
      groups 55-64, 65-74, 75-84 and >=85 years incidence was respectively 33-46, 139
      172, 301-363 and 442-560 per 100,000 person-years amongst men and 32-55, 81-117,
      203-270 and 251-313 per 100,000 person-years amongst women. The 2010 prevalence
      stratified by the same age groups was 293-376, 898-1161, 2524-3011 and 3760-4578
      per 100,000 persons amongst men and 199-351, 618-889, 1910-2433 and 2504-3263 per
      100,000 persons amongst women. CONCLUSIONS: The specific and sensitive
      definitions of disease bracket the true values; the relatively small range
      indicates that the current study provides good estimations of incidence and
      prevalence of Parkinson's disease for recent years in France.

PMID- 25389032
TI  - Simultaneous pancreas and kidney composite graft transplantation with
      retroperitoneal systemic-enteric drainage.
AB  - BACKGROUND: Simultaneous pancreas and kidney transplantation is the treatment of
      choice for diabetes mellitus patients with associated end-stage renal disease.
      Limited vascular access could be encountered in patients with severe
      atherosclerosis, and/or severe obesity and in re-transplant patients. We describe
      a modified technique that facilitates simultaneous pancreas and kidney (SPK)
      composite graft transplantation with retroperitoneal systemic-enteric drainage
      for patients with limited vascular access. MATERIAL/METHODS: Since April 2012, we
      performed a modified technique for 2 patients with limited vascular access. SPK
      composite graft was constructed during the back-table preparation and
      transplanted in the right retroperitoneal space, finally covered by the ascending
      colon and its mesocolon. RESULTS: The 2 patients achieved good pancreas grafts
      function with normal blood glucose immediately after the completion of
      reperfusion. Their kidney grafts have also shown good function. They have not had
      any rejection episodes or postoperative complications after the SPK composite
      graft transplantation. CONCLUSIONS: We propose that simultaneous pancreas and
      kidney composite graft transplantation with retroperitoneal systemic-enteric
      drainage can be a viable option for patients with limited vascular access.

PMID- 25389033
TI  - Neurotrophic tyrosine kinase receptor 1 is a direct transcriptional and
      epigenetic target of IL-13 involved in allergic inflammation.
AB  - Although interleukin (IL)-13 and neurotrophins are functionally important for the
      pathogenesis of immune responses, the interaction of these pathways has not been
      explored. Herein, by interrogating IL-13-induced responses in human epithelial
      cells we show that neurotrophic tyrosine kinase receptor, type 1 (NTRK1), a
      cognate, high-affinity receptor for nerve growth factor (NGF), is an early
      transcriptional IL-13 target. Induction of NTRK1 was accompanied by accumulation
      of activating epigenetic marks in the promoter; transcriptional and epigenetic
      changes were signal transducer and activator of transcription 6 dependent. Using
      eosinophilic esophagitis as a model for human allergic inflammation, we found
      that NTRK1 was increased in inflamed tissue and dynamically expressed as a
      function of disease activity and that the downstream mediator of NTRK1 signaling
      early growth response 1 protein was elevated in allergic inflammatory tissue
      compared with control tissue. Unlike NTRK1, its ligand NGF was constitutively
      expressed in control and disease states, indicating that IL-13-stimulated NTRK1
      induction is a limiting factor in pathway activation. In epithelial cells, NGF
      and IL-13 synergistically induced several target genes, including chemokine (C-C
      motif) ligand 26 (eotaxin-3). In summary, we have demonstrated that IL-13 confers
      epithelial cell responsiveness to NGF by regulating NTRK1 levels by a
      transcriptional and epigenetic mechanism and that this process likely contributes
      to allergic inflammation. 

PMID- 25389034
TI  - Intestinal immunopathology is associated with decreased CD73-generated adenosine
      during lethal infection.
AB  - The ectonucleotidases CD39 and CD73 sequentially degrade the extracellular ATP
      pool and release immunosuppressive adenosine, thereby regulating inflammatory
      responses. This control is likely to be critical in the gastrointestinal tract
      where high levels of ATP are released in particular by commensal bacteria. The
      aim of this study was therefore to evaluate the involvement of the adenosinergic
      regulation in the intestine of mice in steady-state conditions and on acute
      infection with Toxoplasma gondii. We show that both conventional (Tconv) and
      regulatory (Treg) CD4(+) T lymphocytes express CD39 and CD73 in the intestine of
      naive mice. CD73 expression was downregulated during acute infection with T.
      gondii, leading to impaired capacity to produce adenosine. Interestingly, the
      expression of adenosine receptors was maintained and treatment with receptor
      agonists limited immunopathology and dysbiosis, suggesting that the activation of
      adenosine receptors may constitute an efficient approach to control intestinal
      inflammation associated with decreased ectonucleotidase expression. 

PMID- 25389036
TI  - Cyanogel-derived formation of 3 D nanoporous SnO2-MxOy (M=Ni, Fe, Co) hybrid
      networks for high-performance lithium storage.
AB  - Three-dimensional (3 D) nanoporous SnO2 -Mx Oy (M=Fe, Co, Ni, Cu, etc.) hybrid
      networks possess unique compositional and structural features that are beneficial
      to lithium storage and are thus anticipated to meet the performance requirements
      of advanced lithium-ion batteries for transportation and stationary energy
      storage. Herein, a facile, scalable, and versatile cyanogel-derived method for
      the construction of 3 D nanoporous SnO2 -Mx Oy hybrid networks was developed for
      the first time. The formation of 3 D nanoporous SnO2 -NiO, SnO2 -alpha-Fe2 O3 ,
      and SnO2 -NiO-Co3 O4 hybrid networks was illustrated by using Sn-M cyanogels as
      precursors. Moreover, the anodic performance of the 3 D nanoporous SnO2 -NiO
      hybrid network was examined to demonstrate proof of concept. After coating with
      polypyrrole-derived carbon, the SnO2 -NiO@C hybrid network exhibited superior
      lithium-storage capabilities in terms of specific capacity, cycling stability,
      and rate capability. 

PMID- 25389035
TI  - Old questions, new tools: does next-generation sequencing hold the key to
      unraveling intestinal B-cell responses?
AB  - Analysis of the intestinal B-cell system and properties of immunoglobulin A, the
      main antibody isotype produced in the gut, has dominated the rise of mucosal
      immunology as a discipline. Seminal work established concepts describing the
      induction, transport, and function of mucosal antibodies. Still, open questions
      remain and we lack a comprehensive view of how the various sites and pathways of
      immunoglobulin A induction are integrated to respond to gut antigens. Next
      generation sequencing (NGS) offers a novel approach to study B-cell responses,
      which might substantially enhance our tool box to answer key questions in the
      field and to take the next steps toward therapeutic exploitation of the mucosal B
      cell system. In this review we discuss the potential, challenges, and emerging
      solutions for gut B-cell repertoire analysis by NGS. 

PMID- 25389037
TI  - Scientometrics in a changing research landscape: bibliometrics has become an
      integral part of research quality evaluation and has been changing the practice
      of research.

PMID- 25389038
TI  - Ink dating using thermal desorption and gas chromatography/mass spectrometry:
      comparison of results obtained in two laboratories.
AB  - An ink dating method based on solvent analysis was recently developed using
      thermal desorption followed by gas chromatography/mass spectrometry (GC/MS) and
      is currently implemented in several forensic laboratories. The main aims of this
      work were to implement this method in a new laboratory to evaluate whether
      results were comparable at three levels: (i) validation criteria, (ii) aging
      curves, and (iii) results interpretation. While the results were indeed
      comparable in terms of validation, the method proved to be very sensitive to
      maintenances. Moreover, the aging curves were influenced by ink composition, as
      well as storage conditions (particularly when the samples were not stored in
      "normal" room conditions). Finally, as current interpretation models showed
      limitations, an alternative model based on slope calculation was proposed.
      However, in the future, a probabilistic approach may represent a better solution
      to deal with ink sample inhomogeneity. 

PMID- 25389039
TI  - Audit shows that bariatric surgery is cost effective.

PMID- 25389040
TI  - In vitro encapsulation of heterologous dsDNA into human parvovirus B19 virus-like
      particles.
AB  - Virus-like particles (VLPs) have vast potential for applications in nanoscience
      and nanomedicine. These biological nanoparticles may be used for medical imaging,
      vaccination, or tissue-specific delivery of drugs or other bioactive molecules.
      VLPs of Human parvovirus B19 (B19 V) can be assembled in vitro from the
      recombinant VP2 protein. In this research, we describe a simple method for the
      encapsulation of heterologous linear dsDNA fragments of different sizes into B19
      V-VP2 VLPs, in which the DNA and denatured VP2 protein are co-incubated and the
      assembly process is conducted by one dialysis step. Characterization of the
      particles by qPCR demonstrated the encapsulation of dsDNA, and indicates that the
      length of the dsDNA is critical for the encapsulation process. The strategy
      presented here opens the possibility to use this VLPs as a delivery system with
      future therapeutically applications. 

PMID- 25389041
TI  - Propranolol, doxycycline and combination therapy for the treatment of rosacea.
AB  - Doxycycline is the standard systemic treatment for rosacea. Recently, there have
      been a few reports on beta-adrenergic blockers such as nadolol, carvedilol and
      propranolol for suppressing flushing reactions in rosacea. To our knowledge,
      there are no comparative studies of propranolol and doxycycline, and combination
      therapy using both. The aim of this study was to investigate and compare the
      efficacy and safety of monotherapy of propranolol, doxycycline and combination
      therapy. A total of 78 patients who visited Pusan National University Hospital
      and were diagnosed with rosacea were included in this study. Among them, 28
      patients were in the propranolol group, 22 the doxycycline group and 28 the
      combination group. We investigated the patient global assessment (PGA),
      investigator global assessment (IGA), assessment of rosacea clinical score (ARCS)
      and adverse effects. Improvement in PGA and IGA scores from baseline was noted in
      all groups, and the combination therapy was found to be the most effective during
      the entire period, but this was statistically insignificant. The reduction rate
      of ARCS during the treatment period was also highest in the combination group
      (57.4%), followed by the doxycycline group (52.2%) and the propranolol group
      (51.0%). Three patients in the combination group had mild and transient
      gastrointestinal disturbances but there was no significant difference from the
      other groups. We conclude that the combination therapy of doxycycline and
      propranolol is effective and safe treatment for rosacea and successful for
      reducing both flushing and papulation in particular. 

PMID- 25389042
TI  - Biosimilars in psoriasis 2015: what is next?

PMID- 25389043
TI  - Fabrication of polyHEMA grids by micromolding in capillaries for cell patterning
      and single-cell arrays.
AB  - Control of cell adhesion and growth by microfabrication technology and surface
      chemistry is important in an increasing number of applications in biotechnology
      and medicine. In this study, we developed a method to fabricate (2-hydroxyethyl
      methacrylate) (polyHEMA) grids on glass by micromolding in capillaries (MIMIC).
      As a non-fouling biomaterial, polyHEMA was used to inhibit the nonspecific
      bonding of cells, whereas the glass surface provided a cell adhesive background.
      The polyHEMA chemical barrier was directly obtained using MIMIC without surface
      modification, and the microchannel networks used for capillarity were easily
      achieved by reversibly bonding the polydimethylsiloxane (PDMS)mold and the glass.
      After fabrication of the polyHEMA micropattern, individual cytophilic microwells
      surrounded by cytophobic sidewalls were presented on the glass surface. The
      polyHEMA micropattern proved effective in controlling the shape and spreading of
      cells, and square-shaped mouse osteoblast MC3T3-E1 cells were obtained in
      microwell arrays after incubation for 3 days. Moreover, the widths of the
      microwells in this micropattern were optimized for use as single-cell arrays. The
      proposed method could be a convenient tool in the field of drug screening, stem
      cell research, and tissue engineering.

PMID- 25389044
TI  - The effects of Patent Blue dye on peripheral and cerebral oxyhaemoglobin
      saturations.
AB  - We measured the effect of Patent Blue dye on oxyhaemoglobin saturations after
      injection into breast tissue: 40 women had anaesthesia for breast surgery
      maintained with sevoflurane or propofol (20 randomly allocated to each).
      Saturations were recorded with a digital pulse oximeter, in arterial blood
      samples and with a cerebral tissue oximeter before dye injection and 10, 20, 30,
      40, 50, 60, 75, 90, 105 and 120 min afterwards. Patent Blue did not decrease
      arterial blood oxyhaemoglobin saturation, but it did reduce mean (SD) digital and
      cerebral oxyhaemoglobin saturations by 1.1 (1.1) % and 6.8 (7.0) %, p < 0.0001
      for both. The falsely reduced oximeter readings persisted for at least 2 h. The
      mean (SD) intra-operative digital pulse oxyhaemoglobin readings were lower with
      sevoflurane than propofol, 97.8 (1.2) % and 98.8 (1.0) %, respectively, p <
      0.0001. 

PMID- 25389045
TI  - Epidermal growth factor attenuates tubular necrosis following mercuric chloride
      damage by regeneration of indigenous, not bone marrow-derived cells.
AB  - To assess effects of epidermal growth factor (EGF) and pegylated granulocyte
      colony-stimulating factor (P-GCSF; pegfilgrastim) administration on the cellular
      origin of renal tubular epithelium regenerating after acute kidney injury
      initiated by mercuric chloride (HgCl2 ). Female mice were irradiated and male
      whole bone marrow (BM) was transplanted into them. Six weeks later recipient mice
      were assigned to one of eight groups: control, P-GCSF+, EGF+, P-GCSF+EGF+, HgCl2
      , HgCl2 +P-GCSF+, HgCl2 +EGF+ and HgCl2 +P-GCSF+EGF+. Following HgCl2 , injection
      tubular injury scores increased and serum urea nitrogen levels reached uraemia
      after 3 days, but EGF-treated groups were resistant to this acute kidney injury.
      A four-in-one analytical technique for identification of cellular origin, tubular
      phenotype, basement membrane and S-phase status revealed that BM contributed 1%
      of proximal tubular epithelium in undamaged kidneys and 3% after HgCl2 damage,
      with no effects of exogenous EGF or P-GCSF. Only 0.5% proximal tubular cells were
      seen in S-phase in the undamaged group kidneys; this increased to 7-8% after
      HgCl2 damage and to 15% after addition of EGF. Most of the regenerating tubular
      epithelium originated from the indigenous pool. BM contributed up to 6.6% of the
      proximal tubular cells in S-phase after HgCl2 damage, but only to 3.3% after
      additional EGF. EGF administration attenuated tubular necrosis following HgCl2
      damage, and the major cause of this protective effect was division of indigenous
      cells, whereas BM-derived cells were less responsive. P-GCSF did not influence
      damage or regeneration. 

PMID- 25389046
TI  - The attraction of gambling.
AB  - If a repeated gamble is subjectively structured into units each consisting of a
      string of consecutive losses followed by a single win, longer strings will
      necessarily be less valuable. Longer, less valuable strings will be discounted by
      delay more than will shorter, more valuable strings. This implies that the whole
      gamble's expected, delay-discounted value will increase as delay discounting
      increases. With this restructuring, even games of (objectively) negative expected
      value, such as those at casinos, may be subjectively positive. The steeper the
      delay discounting, the greater the subjective value of the gamble (over normal
      ranges of discounting steepness). Frequent gamblers, who value gambles highly,
      would thus be expected to discount delayed rewards more steeply than would
      nongamblers. 

PMID- 25389047
TI  - A novel imprinted transgene located near a repetitive element that exhibits
      allelic imbalance in DNA methylation during early development.
AB  - A mouse line carrying a lacZ transgene driven by the human EEF1A1/EF1 alpha
      promoter was established. Although the promoter is known to show ubiquitous
      activity, only paternal transgene alleles were expressed, resulting in a
      transgene imprinting. At mid-gestation, the promoter sequence was differentially
      methylated, hypomethylated for paternal and hypermethylated for maternal alleles.
      In germline, the promoter was a typical differentially methylated region. After
      fertilization, however, both alleles were hypermethylated. Thus, the differential
      methylation of the promoter required for transgene imprinting was re-established
      during later embryonic development independently of the germline differential
      methylation. Furthermore, also a retroelement promoter closely-flanking imprinted
      transgene and its wild type counterpart displayed similar differential
      methylation during early development. The retroelement promoter was methylated
      differentially also in germline, but in an opposite pattern to the embryonic
      differential methylation. These results suggest that there might be an unknown
      epigenetic regulation inducing transgene imprinting independently of DNA
      methylation in the transgene insertion site. Then, besides CpG dinucleotides, non
      CpG cytosines of the retroelement promoter were highly methylated especially in
      the transgene-active mid-gestational embryos, suggesting that an unusual
      epigenetic regulation might protect the active transgene against de novo
      methylation occurring generally in mid-gestational embryo.

PMID- 25389048
TI  - Intensive intervention can lead to a treatment holiday from biological DMARDs in
      patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by
      inflammation and joint destruction that causes significant morbidity and
      mortality. However, the combined use of methotrexate (MTX), a synthetic disease
      modifying anti-rheumatic drug (sDMARD) and biological DMARDs (bDMARDs) has
      revolutionized treatment of RA and clinical remission or low disease activity
      (LDA) are now realistic targets, achieved by a large proportion of RA patients.
      We are now in a position to evaluate if it is possible to maintain remission or
      LDA while at the same time reducing the burden of treatment on the patient and
      healthcare system. Data are emerging from large, well-conducted studies designed
      to answer this question, shedding light on which patient populations and
      treatment algorithms can survive treatment discontinuation or tapering with low
      risk of disease flare. For early RA, approximately half of early RA patients
      could discontinue TNF-targeted bDMARDs without clinical flare and functional
      impairment after obtaining clinical remission by bDMARDs with MTX. In contrast,
      for established RA, fewer patients sustained remission or LDA after the
      discontinuation of bDMARDs and "deep remission" at the discontinuation was a key
      factor to maintain the treatment holiday of bDMARDs. Thus, this article provides
      a brief outline on withdrawing or tapering bDMARDs once patients have achieved
      remission or LDA in RA.

PMID- 25389049
TI  - Dapagliflozin: a review of its use in patients with type 2 diabetes.
AB  - Dapagliflozin (Forxiga((r)), Farxiga((r))) is an orally administered sodium
      glucose co-transporter-2 (SGLT2) inhibitor used in the management of patients
      with type 2 diabetes. Dapagliflozin reduces renal glucose reabsorption by
      inhibiting the transporter protein SGLT2 in the renal proximal tubule, thereby
      increasing urinary glucose excretion and reducing blood glucose levels. Its
      mechanism of action is independent of insulin secretion or action; therefore,
      dapagliflozin provides complementary therapy when used in combination with other
      antihyperglycaemic drugs. This article updates an earlier review of dapagliflozin
      and focuses on longer-term efficacy and tolerability data (e.g. from extensions
      of earlier clinical trials), as well as data from studies in special patient
      populations (e.g. history of cardiovascular disease). Numerous well-designed
      clinical trials with dapagliflozin, primarily as add-on therapy for 24 weeks (but
      also as monotherapy or initial combination therapy), have consistently
      demonstrated reductions in glycosylated haemoglobin, fasting plasma glucose
      levels and bodyweight. Extensions of these trials show the effects are maintained
      over longer-term follow-up periods of ~1-4 years and dapagliflozin is generally
      well tolerated. Dapagliflozin has a low risk of hypoglycaemia, although the
      incidence varies depending on background therapy, and genital mycotic infections
      (particularly in women) are the most common adverse events. Dapagliflozin is not
      recommended in patients with moderate or severe renal impairment. In view of its
      unique mechanism of action and now well-established efficacy and tolerability
      profile, dapagliflozin is a useful treatment option in the management of type 2
      diabetes, although its effects on diabetic complications remain to be evaluated.

PMID- 25389050
TI  - Heterogeneous nuclear ribonucleoprotein E1 regulates protein disulphide isomerase
      translation in oxidized low-density lipoprotein-activated endothelial cells.
AB  - AIMS: Endothelium-derived protein disulphide isomerase (PDI) is required for
      thrombus formation in vivo. But, how to control PDI overproduction in oxidized
      low-density lipoprotein (oxLDL)-activated vascular endothelial cells (VECs) is
      not well understood. In this study, we try to answer this question using our
      newly identified activator of mTOC1 3-benzyl-5-((2-nitrophenoxy) methyl)
      dihydrofuran-2 (3H)-one (3BDO) that has been shown to protect VECs. METHODS:
      First, we performed a proteomics analysis on the oxLDL-activated vascular VECs in
      the presence or absence of 3BDO. Next, we constructed the heterogeneous nuclear
      ribonucleoprotein E1 (hnRNP E1) mutants at Ser43 and used the RNA-ChIP technique
      to investigate the relationship between hnRNP E1 and PDI production. Furthermore,
      we examined the effect of 3BDO on oxLDL-altered phosphorylation of Akt1 and Akt2.
      Finally, we studied the effect of 3BDO on oxLDL-altered PDI protein level in
      apolipoprotein E(-/-) mice with advanced atherosclerosis. RESULTS: In VECs, oxLDL
      increased PDI protein level, induced hnRNP E1 phosphorylation at Ser43,
      suppressed the binding of hnRNP E1 to PDI 5'UTR and induced the phosphorylation
      of Akt2 but not Akt1. All of these processes were blocked by 3BDO. Importantly,
      Ser43 mutant of hnRNP E1 inhibited the increase of PDI protein level and the
      decrease of the binding of hnRNP E1 and PDI 5'UTR induced by oxLDL. Furthermore,
      3BDO suppressed oxLDL-induced PDI protein increase in the serum and plaque
      endothelium of apolipoprotein E(-/-) mice. CONCLUSION: hnRNP E1 is a new
      regulator of PDI translation in oxLDL-activated VECs, and 3BDO is a powerful
      agent for controlling PDI overproduction.

PMID- 25389051
TI  - Evidence for BRAF V600E and H3F3A K27M double mutations in paediatric glial and
      glioneuronal tumours.

PMID- 25389053
TI  - Phenolic composition and related antioxidant properties in differently colored
      lettuces: a study by electron paramagnetic resonance (EPR) kinetics.
AB  - Differently colored lettuce (Lactuca sativa L.) cultivars (green, green/red, and
      red) were studied to correlate their phenolic composition with their antioxidant
      kinetic behavior. Electron paramagnetic resonance (EPR) was employed to monitor
      decay kinetics of 1,1-diphenyl-2-picrylhydrazyl (DPPH(*)), which allowed the
      identification of three differently paced antioxidants. The results showed that
      as long as lettuce had higher red pigmentation, the hydrophilic antioxidant
      capacity increased together with the contents in free and conjugated phenolic
      acids, free and conjugated flavonoids, and anthocyanins. EPR allowed the
      identification of slow-rate antioxidants in green and green/red cultivars,
      intermediate-rate antioxidants in green, green/red, and red cultivars, and fast
      rate antioxidants in green/red and red cultivars. At present, the different
      kinetic behaviors cannot be attributed to a specific antioxidant, but it is
      suggested that the flavonoid quercetin accounted for the majority of the
      intermediate-rate antioxidants, whereas the anthocyanins accounted for the
      majority of the fast-rate antioxidants. 

PMID- 25389054
TI  - Measuring health-promoting behaviors: cross-cultural validation of the Health
      Promoting Lifestyle Profile-II.
AB  - PURPOSE: Individual lifestyles have emerged as valuable health constructs. This
      study aims to psychometrically test the Portuguese (European) version of the
      Health-Promoting Lifestyle Profile-II. METHODS: After an adequate linguistic and
      cultural adaptation of the Health-Promoting Lifestyle Profile-II scale, their
      psychometric properties were assessed (N = 889) by Cronbach's alpha and
      confirmatory factor analysis. FINDINGS: Results showed an adequate fit to a 52
      item, six-factor structure. A global alpha of .925 was obtained. CONCLUSIONS: The
      Portuguese version demonstrated good validity and reliability in a wide adult
      sample, and can thus be applied to the Portuguese population. IMPLICATIONS FOR
      NURSING PRACTICE: This instrument is useful as an evaluation tool for health
      promoting lifestyles and as an instrument for testing the effectiveness of health
      promoting programs.

PMID- 25389052
TI  - Amelioration of cisplatin-induced nephrotoxicity in rats by triterpenoid saponin
      of Terminalia arjuna.
AB  - BACKGROUND: Cisplatin is a potent anti-tumor compound. Nephrotoxicity-inducing
      oxidative stress is a common side effect. This study was conducted to find out
      whether, the triterpenoid saponin of Terminalia arjuna (TA), Arjunolic acid which
      is a natural antioxidant, could prevent cisplatin-induced renal toxicity and if
      so, explore its possible renoprotective mechanism. METHODS: Thirty male Sprague
      Dawley rats were divided into three groups: CONTROL GROUP: rats received saline
      injection, cisplatin group: rats injected intraperitoneally with 7 mg/kg
      cisplatin and Arjunolic acid group: rats received 20 mg/kg Arjunolic acid daily
      for 10 days with cisplatin injection on day 5. Serum creatinine and blood urea
      nitrogen (BUN) were determined and kidney sections were obtained for
      histopathology. Oxidative stress was evaluated in kidney homogenates by measuring
      malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels.
      Renal gene expressions of transforming growth factor-beta (TGF-beta), nuclear
      factor-kappa B (NF-kappaB), kidney injury molecule-1 (Kim-1) and B cell lymphoma
      2 (Bcl-2) were estimated. RESULTS: Cisplatin-treated rats showed a significant
      reduction in renal GSH and a significant elevation of serum creatinine, BUN, MDA
      and NO renal levels when compared with control. Moreover, upregulation of TGF
      beta, NF-kappaB and Kim-1 along with downregulation of Bcl-2 renal expressions
      were also observed in cisplatin-treated rats in comparison to control. All these
      markers were significantly reversed by TA triterpenoid saponin administration.
      CONCLUSION: Arjunolic acid ameliorated the nephrotoxic biochemical changes
      induced by cisplatin supporting its renoprotective effects which may be mediated
      by attenuation of oxidative stress markers, downregulation of renal expressions
      of fibrotic (TGF-beta), inflammatory (NF-kappaB) and kidney injury (Kim-1)
      markers along with upregulation of renal antiapoptotic marker (Bcl-2) gene
      expressions.

PMID- 25389055
TI  - Neonatal procedural pain can be assessed by computer software that has good
      sensitivity and specificity to detect facial movements.
AB  - AIM: The difficulty in assessing pain during the neonatal period is one of the
      main obstacles for appropriate analgesia in intensive care units. The aim of this
      study was to develop and validate computer software to monitor neonatal facial
      movements of pain in real time. METHODS: The software was developed in the Delphi
      integrated development environment and provides real-time image analysis during
      monitoring, based on image recognition of pain-related facial actions. To
      validate the software performance, facial images were obtained during the
      monitoring of 30 neonates who were subjected to painful procedures related to
      daily care management. Of the 5644 images identified and analysed by the
      software, 360 images - 12 per infant - were randomly selected and assessed by six
      healthcare professionals with experience of recognising neonatal pain. RESULTS:
      The agreement between the examiners and the software assessment was excellent
      (kappa = 0.975). The software exhibited 85% sensitivity and 100% specificity in
      detecting neutral facial expressions in the resting state and 100% sensitivity
      and specificity in detecting pain during painful procedures. CONCLUSION: It is
      possible to assess neonatal procedural pain using computer software that has good
      sensitivity and specificity to detect facial movements.

PMID- 25389056
TI  - Sarcopenia adversely impacts postoperative complications following resection or
      transplantation in patients with primary liver tumors.
AB  - BACKGROUND: Sarcopenia is a surrogate marker of patient frailty that estimates
      the physiologic reserve of an individual patient. We sought to investigate the
      impact of sarcopenia on short- and long-term outcomes in patients having
      undergone surgical intervention for primary hepatic malignancies. METHODS: Ninety
      six patients who underwent hepatic resection or liver transplantation for HCC or
      ICC at the John Hopkins Hospital between 2000 and 2013 met inclusion criteria.
      Sarcopenia was assessed by the measurement of total psoas major volume (TPV) and
      total psoas area (TPA). The impact of sarcopenia on perioperative complications
      and survival was assessed. RESULTS: Mean age was 61.9 years and most patients
      were men (61.4 %). Mean adjusted TPV was lower in women (23.3 cm(3)/m) versus men
      (34.9 cm(3)/m) (P < 0.01); 47 patients (48.9 %) had sarcopenia. The incidence of
      a postoperative complication was 40.4 % among patients with sarcopenia versus
      18.4 % among patients who did not have sarcopenia (P = 0.01). Of note, all
      Clavien grade >=3 complications (n = 11, 23.4 %) occurred in the sarcopenic
      group. On multivariable analysis, the presence of sarcopenia was an independent
      predictive factor of postoperative complications (OR = 3.06). Sarcopenia was not
      associated with long-term survival (HR = 1.23; P = 0.51). CONCLUSIONS:
      Sarcopenia, as assessed by TPV, was an independent factor predictive of
      postoperative complications following surgical intervention for primary hepatic
      malignancies.

PMID- 25389057
TI  - Minimally invasive pancreatectomy for cancer: a critical review of the current
      literature.
AB  - Minimally invasive surgery (MIS) has transformed operative practices by offering
      patients procedures with reduced hospital stay and recovery compared to that of
      open operations. In spite of the advantages of a MIS approach, the application to
      pancreatectomy has only recently emerged. This review aims to analyze and discuss
      available comparative studies as they relate to resection techniques for
      treatment of malignant disease. A PubMed search was used to obtain original
      studies and meta-analyses relating to MIS pancreatectomy from 2008 to 2013.
      Several studies were identified that reported on the application of MIS
      specifically to the treatment of cancer, many of which were retrospective, single
      institution studies. Notwithstanding an inherent selection bias, several studies
      suggest that MIS can provide equivalent R0 resection rates, number of lymph nodes
      harvested, and survival to that of open resection. Furthermore, parameters such
      as blood loss and length of stay are significantly reduced in patients treated
      with MIS. The current literature supports the conclusion that MIS is safe and
      effective as a treatment for cancer in well-selected patients in the hands of
      experienced surgeons. However, the published studies to date are observational in
      nature and therefore higher quality studies will be needed to support the
      application and generalizability of MIS in the treatment of pancreatic
      malignancies.

PMID- 25389058
TI  - In vitro antihyperlipidemic potential of triterpenes from stem bark of Protorhus
      longifolia.
AB  - Two lanostane triterpenes, 3beta-hydroxylanosta-9,24-dien-21-oic acid (1) and
      methyl-3beta-hydroxylanosta-9,24-dien-21-oate (2), were isolated from the stem
      bark of Protorhus longifolia. Their structures were deduced on the basis of
      spectroscopic analysis (NMR, HRMS, IR). This study investigated the in vitro anti
      adipogenic activity of the two triterpenes. Their inhibitory activity was
      evaluated on selected lipid digestive enzymes (pancreatic lipase and cholesterol
      esterase). The inhibitory activity of the compounds on hormone-sensitive lipase
      and their ability to bind bile acids were also evaluated. The effect of the
      compounds on glucose uptake in C2C12 muscle cells and 3T3-L1 adipocytes, and on
      triglyceride accumulation in 3T3-L1 adipocytes was investigated. The triterpenes
      effectively inhibited the activities of the enzymes with IC50 values ranging from
      0.04 to 0.31 mg/mL. The compounds showed a high affinity for secondary bile
      acids. Both compounds stimulated glucose uptake in C2C12 muscle cells and 3T3-L1
      adipocytes. Compound 1 significantly reduced triglyceride accumulation in mature
      differentiated 3T3-L1 adipocytes. It is apparent that these lanostane triterpenes
      enhance glucose uptake and suppress adipogenesis, which together with their
      inhibitory effects on lipid digestive enzymes suggests that they have
      antihyperlipidemic potential. 

PMID- 25389059
TI  - Influence of extra virgin olive oil on blood pressure and kidney angiotensinase
      activities in spontaneously hypertensive rats.
AB  - High-fat diets are associated with the development of cardiovascular diseases.
      The efficacy of the current strategies of treatment is still not entirely
      satisfactory, and new approaches are being considered. To analyze the beneficial
      effects of extra virgin olive oil as a major component of the Mediterranean diet,
      we studied systolic blood pressure and angiotensinase activities, since this
      enzyme is involved in the metabolism of angiotensins, in the kidney of
      hypertensive rats fed during 12 weeks with a diet enriched with extra virgin
      olive oil compared with a standard diet. As a reflex of oxidative stress, 8
      isoprostanes and nitric oxide were quantified in urine. Results demonstrated a
      progressive increase in systolic blood pressure until the end of the feeding
      period in both groups. However, this increase was delayed in the extra virgin
      olive oil group until week six, with the systolic blood pressure being always
      lower in this group. Nitric oxide and 8-isoprostanes were lower in the extra
      virgin olive oil group. While we can deduce a higher formation of angiotensin 2
      10 in the renal cortex, a higher availability of angiotensin II may be presumed
      in the renal medulla of animals fed an extra virgin olive oil diet than in
      animals fed a standard diet. Our results support the beneficial influence of
      extra virgin olive oil on cardiovascular function and suggest that the
      Mediterranean diet may be beneficial in itself but it may also be an effective
      tool in the treatment of hypertension. 

PMID- 25389060
TI  - Accelerated NMR spectroscopy with low-rank reconstruction.
AB  - Accelerated multi-dimensional NMR spectroscopy is a prerequisite for high
      throughput applications, studying short-lived molecular systems and monitoring
      chemical reactions in real time. Non-uniform sampling is a common approach to
      reduce the measurement time. Here, a new method for high-quality spectra
      reconstruction from non-uniformly sampled data is introduced, which is based on
      recent developments in the field of signal processing theory and uses the so far
      unexploited general property of the NMR signal, its low rank. Using experimental
      and simulated data, we demonstrate that the low-rank reconstruction is a viable
      alternative to the current state-of-the-art technique compressed sensing. In
      particular, the low-rank approach is good in preserving of low-intensity broad
      peaks, and thus increases the effective sensitivity in the reconstructed spectra.

PMID- 25389061
TI  - Improving nutritional status in a pediatric cystic fibrosis center.
AB  - BACKGROUND: The nutritional status of patients with cystic fibrosis (CF) is
      strongly associated with pulmonary function, respiratory status and survival.
      Malnutrition could result from a discrepancy between energy needs and food intake
      while malabsorption results from pancreatic insufficiency which occurs in 85% of
      people with CF. METHODS: A quality improvement (QI) project was designed to
      improve the nutritional status of patients with CF with low Body Mass Index (BMI)
      between 3 and 19 years of age. An algorithm was developed which included clinic
      based assessments of patients' nutritional status and periodic assessment by a
      dietitian, social worker and/or psychologist during the project. Gastrostomy tube
      placement and feeding was offered as a last resort to improve caloric intake.
      RESULTS: 173 patients seen during January-June, 2010, were included in this
      project. They were classified into four BMI groups and data were collected
      quarterly through June, 2012. The project target population (BMI percentile <=
      24) had a median BMI percentile at the start of the project of 11.8. At the end
      of the project median BMI percentile was 22 (46% improvement). CONCLUSION:
      Improving nutrition and BMI for patients with CF is achievable. There must be a
      motivated, multi-disciplinary team that includes patients and families. A patient
      specific combination of interventions must be used. These interventions could be
      quite basic for patients with BMI percentile >= 25, yet more elaborate for
      patients with BMI percentile <25. Clinic-based algorithms such as ours can
      successfully improve the BMI percentile in patients with CF.

PMID- 25389062
TI  - Icariin inhibits foam cell formation by down-regulating the expression of CD36
      and up-regulating the expression of SR-BI.
AB  - Icariin is an important pharmacologically active flavonol diglycoside that can
      inhibit inflammation in lipopolysaccharide (LPS)-stimulated macrophages. However,
      little is known about the molecular mechanisms underlying the inhibitory effect
      of Icariin in the formation of foam cells. In this study, macrophages were
      cultured with LPS and oxidized low-density lipoprotein (oxLDL) in the presence or
      absence of Icariin. RT-PCR and western blot were used to detect the levels of
      mRNA and protein expression of CD36, scavenger receptor class B type I (SR-BI)
      and the phosphorylation of p38MAPK. It was demonstrated that 4 uM or 20 uM
      Icariin treatment significantly inhibited the cholesterol ester (CE)/total
      cholesterol (TC) and oxLDL-mediated foam cell formation (P < 0.05). The binding
      of oxLDL to LPS-activated macrophages was also significantly hindered by Icariin
      (P < 0.05). Furthermore, Icariin down-regulated the expression of CD36 in LPS
      activated macrophages in a dose-dependent manner and CD36 over-expression
      restored the inhibitory effect of Icariin on foam cell formation. The
      phosphorylation of p38MAPK was reduced by Icariin, indicating that Icariin
      reduced the expression of CD36 through the p38MAPK pathway. In addition, Icariin
      up-regulated SR-BI protein expression in a dose-dependent manner, and SR-BI gene
      silencing restored the inhibitory effect of Icariin on foam cell formation. These
      data demonstrate that Icariin inhibited foam cell formation by down-regulating
      the expression of CD36 and up-regulating the expression of SR-BI. Therefore, our
      findings provide a new explanation as to why Icariin could inhibit
      atherosclerosis.

PMID- 25389063
TI  - Hysterosalpingography: an imaging Atlas with cross-sectional correlation.
AB  - Hysterosalpingography (HSG) provides a unique combination of both fallopian tube
      and uterine cavity evaluation. A comprehensive understanding of both HSG and
      correlative cross-sectional imaging findings are essential radiologic skills.
      This article will review the spectrum of technical artifacts, anatomic variants,
      congenital uterine anomalies, uterine and tubal pathology, and postsurgical
      findings as they appear on HSG. Additionally, correlation with MR and ultrasound
      images is provided. This review article serves as a reference for residents new
      to HSG as well as staff who perform and interpret HSG infrequently. 

PMID- 25389065
TI  - Defensive weapons and defense signals in plants: some metabolites serve both
      roles.
AB  - The defense of plants against herbivores and pathogens involves the participation
      of an enormous range of different metabolites, some of which act directly as
      defensive weapons against enemies (toxins or deterrents) and some of which act as
      components of the complex internal signaling network that insures that defense is
      timed to enemy attack. Recent work reveals a surprising trend: The same compounds
      may act as both weapons and signals of defense. For example, two groups of well
      studied defensive weapons, glucosinolates and benzoxazinoids, trigger the
      accumulation of the protective polysaccharide callose as a barrier against aphids
      and pathogens. In the other direction, several hormones acting in defense
      signaling (and their precursors and products) exhibit activity as weapons against
      pathogens. Knowing which compounds are defensive weapons, which are defensive
      signals and which are both is vital for understanding the functioning of plant
      defense systems. 

PMID- 25389064
TI  - Identification of proteins capable of metal reduction from the proteome of the
      Gram-positive bacterium Desulfotomaculum reducens MI-1 using an NADH-based
      activity assay.
AB  - Understanding of microbial metal reduction is based almost solely on studies of
      Gram-negative organisms. In this study, we focus on Desulfotomaculum reducens MI
      1, a Gram-positive metal reducer whose genome lacks genes with similarity to any
      characterized metal reductase. Using non-denaturing separations and mass
      spectrometry identification, in combination with a colorimetric screen for
      chelated Fe(III)-NTA reduction with NADH as electron donor, we have identified
      proteins from the D. reducens proteome not previously characterized as iron
      reductases. Their function was confirmed by heterologous expression in
      Escherichia coli. Furthermore, we show that these proteins have the capability to
      reduce soluble Cr(VI) and U(VI) with NADH as electron donor. The proteins
      identified are NADH : flavin oxidoreductase (Dred_2421) and a protein complex
      composed of oxidoreductase flavin adenine dinucleotide/NAD(P)-binding subunit
      (Dred_1685) and dihydroorotate dehydrogenase 1B (Dred_1686). Dred_2421 was
      identified in the soluble proteome and is predicted to be a cytoplasmic protein.
      Dred_1685 and Dred_1686 were identified in both the soluble as well as the
      insoluble protein fraction, suggesting a type of membrane association, although
      PSORTb predicts both proteins are cytoplasmic. This study is the first functional
      proteomic analysis of D. reducens and one of the first analyses of metal and
      radionuclide reduction in an environmentally relevant Gram-positive bacterium.

PMID- 25389066
TI  - Component-resolved diagnosis: performance of specific IgE to Alternaria compared
      to Alt a 1.

PMID- 25389067
TI  - Light-regulated microRNAs.
AB  - In addition to exposure to passive diurnal cycles of sunlight, humans are also
      subjected to intentional acute exposure to other types of electromagnetic
      radiation (EM). Understanding the molecular mechanisms involved in the
      physiological, pathological and therapeutic responses to exposure to radiation is
      an active area of research. With the advent of methods to readily catalog and
      identify patterns of changes in gene expression, many studies have reported
      changes in gene expression upon exposure of various human and mouse cells in
      vitro, whole experimental organisms such as mice and parts of human body.
      However, the molecular mechanisms underlying these broad ranging changes in gene
      expression are not yet fully understood. MicroRNAs, which are short, noncoding
      RNAs that regulate gene expression by targeting many messenger RNAs, are also
      emerging as important mediators of radiation-induced changes in gene expression
      and hence critical for the manifestation of light-induced cellular phenotypes and
      physiological responses. In this article, we review available knowledge on
      microRNAs implicated in responses to various forms of solar and other EM
      radiation. Based on this knowledge, we elaborate some unifying themes in the
      regulation and functions of some of these miRNAs. 

PMID- 25389068
TI  - Characterization of incomplete vitellogenin (VgC) in the Indian freshwater
      murrel, Channa punctatus (Bloch).
AB  - A novel incomplete vitellogenin (VgC) was purified from the plasma of estradiol
      treated male murrel, Channa punctatus, by gel filtration chromatography. The
      native mass of VgC protein was 180 kDa, and it resolved as a single peptide of
      100 kDa on SDS-PAGE. The peptide on subjecting to matrix-assisted laser
      desorption/ionization-time of flight produced a peptide mass fingerprint. On
      tandem mass spectrometry, some of these peptides showed mass to charge (m/z)
      ratio and amino acid sequence similarity with VgC peptides of other teleosts.
      Phylogenetic analysis revealed a similarity of murrel VgC with fish species of
      the order Perciformes. Semi-quantitative RT-PCR assay was developed to study
      expression of vgc gene at variable levels of estradiol exposure. Presence of VgC
      in males indicates that fish has been exposed to estrogens; hence, it can be used
      as a biomarker for estrogenic exposure.

PMID- 25389070
TI  - Soluble porous coordination polymers by mechanochemistry: from metal-containing
      films/membranes to active catalysts for aerobic oxidation.
AB  - Soluble porous coordination polymers from mechanochemical synthesis are presented
      through a coordination polymerization between highly contorted, rigid tetraphenol
      and a broad variety of transition metal ions. These polymers can be easily cast
      as metal-containing films or freestanding membranes. Importantly, as-made
      coordination polymers are highly active and stable in the aerobic oxidation of
      allylic C-H bonds.

PMID- 25389071
TI  - Hyponatraemia on admission to hospital is associated with increased long-term
      risk of mortality in survivors of myocardial infarction.
AB  - BACKGROUND: Hyponatremia is associated with an increased risk of mortality in
      patients with heart failure and in acute ST-segment elevation myocardial
      infarction (STEMI). The aim was to assess the impact of hyponatremia on admission
      on long-term mortality of patients with first ever STEMI or non-STEMI (NSTEMI).
      DESIGN: This was a longitudinal observation study METHODS: The study population
      consisted of 3558 patients, aged 25-74 years, with an incident acute myocardial
      infarction (AMI) in the years 2000-2008 who survived for at least 28 days. All
      consecutive patients were registered through the Cooperative Health Research in
      the Region of Augsburg (KORA) Myocardial Infarction Registry. Serum sodium levels
      were obtained on admission. The association with long-term-mortality was examined
      using Cox regression models. RESULTS: Hyponatraemia, defined as a sodium level
      less than 136 mmol/l, was present in 658 (18.5%) patients on admission. During a
      median follow-up period of six years (interquartile range (IQR) 4.0-8.2 years),
      526 patients (14.8%) died. Hyponatraemia was significantly associated with long
      term mortality by an 83% higher risk in the age- and sex-adjusted analysis. After
      further adjustment for reduced left ventricular ejection fraction (LVEF),
      glomerular filtration rate, haemoglobin, hypertension, hyperlipidaemia, any
      recanalization therapy, diabetes, medication with diuretics and angiotensin
      converting enzyme (ACE) inhibitor/angiotensin-receptor blocker before admission
      and other parameters hyponatraemia remained a strong predictor for higher long
      term mortality (hazard ratio 1.61; 95% confidence interval 1.32-1.97).
      CONCLUSIONS: Patients with incident AMI and hyponatraemia on admission showed a
      significantly higher risk of long-term mortality than patients without. This
      strong predictive value was independent of a number of prognostic factors,
      including diabetes, glomerular filtration rate or reduced LVEF.

PMID- 25389072
TI  - Heart failure is associated with exaggerated endothelial ischaemia-reperfusion
      injury and attenuated effect of ischaemic preconditioning.
AB  - BACKGROUND: Reperfusion is mandatory after ischaemia, but it also triggers
      ischaemia-reperfusion (IR)-injury. It is currently unknown whether heart failure
      alters the magnitude of IR-injury. Ischaemic preconditioning can limit IR-injury.
      Since ischaemic preconditioning is typically applied in subjects at risk for
      cardiovascular complications, it is of clinical importance to understand its
      efficacy in heart failure patients. OBJECTIVE: To examine the magnitude of
      endothelial IR-injury, and the ability of ischaemic preconditioning to protect
      against endothelial IR-injury in heart failure. METHODS: We included 15 subjects
      with heart failure (67 +/- 10 years, New York Heart Association class II/III) and
      15 healthy, age- and sex-matched controls (65 +/- 9 years). We examined brachial
      artery endothelial function using flow-mediated dilation before and after arm IR
      (induced by 5-min ischaemic handgrip exercise +15 min reperfusion). IR was
      preceded by ischaemic preconditioning (consisting in three cycles of 5-min upper
      arm cuff inflation to 220 mmHg) or no inflation. RESULTS: A significant
      interaction-effect was found for the change in flow-mediated dilation after IR
      between groups (two-way ANOVA interaction-effect: p = 0.01). Whilst post-hoc
      analysis revealed a significantly decline in flow-mediated dilation in both
      groups (p < 0.05), the decline in flow-mediated dilation in heart failure
      patients (6.2 +/- 3.6% to 3.3 +/- 1.8%) was significantly larger than that
      observed in controls (4.9 +/- 2.1 to 4.1 +/- 2.0). Neither in heart failure
      patients nor controls was the decrease in flow-mediated dilation after IR altered
      by ischaemic preconditioning (three-way ANOVA interaction: p = 0.87). CONCLUSION:
      We found that patients with heart failure are associated with exaggerated
      endothelial IR-injury compared with age- and sex-matched, healthy controls, which
      may contribute to the poor clinical prognosis in heart failure. Furthermore, we
      found no protective effect of ischaemic preconditioning (3 * 5-min forearm
      ischaemia) against endothelial IR-injury in heart failure patients.

PMID- 25389073
TI  - Intellectual and academic performance in children undergoing solid organ
      pretransplant evaluation.
AB  - Although prior research has shown lower intellectual functioning across pediatric
      solid organ transplant recipients relative to matched siblings or norm
      comparisons, few studies have assessed intellectual and academic performance
      prior to transplant across organ groups. The current data examine intellectual
      and academic functioning in children being evaluated for kidney, liver, or heart
      transplant. This investigation included intellectual and academic testing data
      from 195 children and adolescents between the ages of six and 19 yr evaluated for
      solid organ transplantation. Across organ groups, patients' intellectual
      functioning as estimated by the WASI/WASI-II at the time of pretransplant
      evaluation was within the average range, but lower compared to test norms.
      Patients demonstrated lower estimates of word reading, math computation, and
      spelling skills compared to the normal population, with the exception of heart
      patients' word reading and spelling skills and liver patients' spelling scores.
      Cognitive and academic impairments exist in children prior to transplantation.
      Findings emphasize the support that patients may require to manage the
      complicated medical regimen and succeed academically. Routine cognitive and
      academic assessment can inform healthcare providers regarding transplant
      patients' capacity to take on increasing medical responsibility and successfully
      reintegrate into the school environment.

PMID- 25389074
TI  - Share with women. Fetal heart rate monitoring in labor.

PMID- 25389075
TI  - Patient satisfaction in Caucasian and Mediterranean open rhinoplasty using the
      tongue-in-groove technique: prospective statistical analysis of change in
      subjective body image in relation to nasal appearance following aesthetic
      rhinoplasty.
AB  - OBJECTIVES/HYPOTHESIS: Tongue-in-groove (TIG) is a conservative but powerful
      surgical suture technique to control shape, rotation, and projection of the nasal
      tip. In this study, statistical analyses were performed to determine the
      aesthetical and functional effectiveness of TIG rhinoplasty. STUDY DESIGN:
      Prospective cohort study including 110 Caucasian or Mediterranean aesthetic
      rhinoplasty patients treated by one surgeon between 2007 and 2012, with a 1-year
      follow-up. METHODS: Data were collected using the Utrecht Questionnaire, a
      validated instrument routinely offered to our patients before and 1 year after
      surgery. Aesthetic results were reflected by change in subjective body image in
      relation to nasal appearance, scored on five aesthetic questions and a 10-cm
      visual analog scale (VAS). Functional results were determined by change in
      subjective nasal airway patency, scored on a 10-cm VAS for both sides. RESULTS:
      The mean aesthetic sum score (5, low burden-25, high burden) significantly
      improved from 14.01 to 6.54 (P <.01). The mean aesthetic VAS score (0, very ugly
      10, very nice) significantly improved from 3.35 to 7.78 (P < .01). The mean
      functional VAS score (0, very bad-10, very good) showed a small but significant
      improvement on both sides (left, 6.83-7.96; right, 6.88-7.80; P <.01).
      CONCLUSION: Statistical analysis of quantified subjective data on nasal
      aesthetics and function show that TIG is a reliable technique that can help to
      deliver consistently good results in Caucasian and Mediterranean patients seeking
      aesthetic rhinoplasty. A small additional functional improvement can be expected.

PMID- 25389076
TI  - Cohort study of corticosteroid use and risk of hospital admission for
      diverticular disease.
AB  - BACKGROUND: Medication has been suggested as a potential risk factor for
      diverticular disease. The objective of this study was to investigate the
      association between the intake of corticosteroids, indometacin or aspirin and
      diverticular disease. METHOD: This was a prospective population-based cohort
      study of middle-aged women in the Swedish Mammography Cohort. Use of
      corticosteroids (oral or inhaled), indometacin or aspirin in 1997 was determined
      from questionnaires. Cases of diverticular disease were identified from the
      Swedish national registers until the end of 2010. The relative risk (RR) of
      diverticular disease requiring hospital admission according to the use of
      medication was estimated using Cox proportional hazards models, adjusted for age,
      body mass index, physical activity, fibre intake, diabetes, hypertension,
      alcohol, smoking and education. RESULTS: A total of 36 586 middle-aged women in
      the Swedish Mammography Cohort were included, of whom 674 (1.8 per cent) were
      hospitalized with diverticular disease at least once. Some 7.2 per cent of women
      reported intake of oral corticosteroids and 8.5 per cent use of inhaled
      corticosteroids. In multivariable analysis, women who reported oral
      corticosteroid intake had a 37 per cent (RR 1.37, 95 per cent c.i. 1.06 to 1.78;
      P = 0.012) increased risk of diverticular disease compared with those who
      reported no intake at all. Use of inhaled corticosteroids was associated with an
      even more pronounced increase in risk of 71 per cent (RR 1.71, 1.36 to 2.14; P <
      0.001). There was a significant dose-response relationship, with the risk
      increasing with longer duration of inhaled corticosteroids (P for trend < 0.001).
      Use of indometacin (2.5 per cent of women) or aspirin (44.2 per cent) did not
      influence the risk. CONCLUSION: There was a significant relationship between
      corticosteroids (especially inhaled) and diverticular disease requiring hospital
      admission.

PMID- 25389077
TI  - Nosology, ontology and promiscuous realism.
AB  - Medics may consider worrying about their metaphysics and ontology to be a waste
      of time. I will argue here that this is not the case. Promiscuous realism is a
      metaphysical position which holds that multiple, equally valid, classification
      schemes should be applied to objects (such as patients) to capture different
      aspects of their complex and heterogeneous nature. As medics at the bedside may
      need to capture different aspects of their patients' problems, they may need to
      use multiple classification schemes (multiple nosologies), and thus consider
      adopting a different metaphysics to the one commonly in use.

PMID- 25389078
TI  - Age estimation in forensic anthropology: quantification of observer error in
      phase versus component-based methods.
AB  - The purpose of this study was to assess observer error in phase versus component
      based scoring systems used to develop age estimation methods in forensic
      anthropology. A method preferred by forensic anthropologists in the AAFS was
      selected for this evaluation (the Suchey-Brooks method for the pubic symphysis).
      The Suchey-Brooks descriptions were used to develop a corresponding component
      based scoring system for comparison. Several commonly used reliability statistics
      (kappa, weighted kappa, and the intraclass correlation coefficient) were
      calculated to assess observer agreement between two observers and to evaluate the
      efficacy of each of these statistics for this study. The linear weighted kappa
      was determined to be the most suitable measure of observer agreement. The results
      show that a component-based system offers the possibility for more objective
      scoring than a phase system as long as the coding possibilities for each trait do
      not exceed three states of expression, each with as little overlap as possible. 

PMID- 25389079
TI  - Differences in the metabolic response to temperature acclimation in nine-spined
      stickleback (Pungitius pungitius) populations from contrasting thermal
      environments.
AB  - Metabolic responses to temperature changes are crucial for maintaining the energy
      balance of an individual under seasonal temperature fluctuations. To understand
      how such responses differ in recently isolated populations (<11,000 years), we
      studied four Baltic populations of the nine-spined stickleback (Pungitius
      pungitius L.) from coastal locations (seasonal temperature range, 0-29 degrees C)
      and from colder, more thermally stable spring-fed ponds (1-19 degrees C).
      Salinity and predation pressure also differed between these locations. We
      acclimatized wild-caught fish to 6, 11, and 19 degrees C in common garden
      conditions for 4-6 months and determined their aerobic scope and hepatosomatic
      index (HSI). The freshwater fish from the colder (2-14 degrees C), predator-free
      pond population exhibited complete temperature compensation for their aerobic
      scope, whereas the coastal populations underwent metabolic rate reduction during
      the cold treatment. Coastal populations had higher HSI than the colder pond
      population at all temperatures, with cold acclimation accentuating this effect.
      The metabolic rates and HSI for freshwater fish from the pond with higher
      predation pressure were more similar to those of the coastal ones. Our results
      suggest that ontogenic effects and/or genetic differentiation are responsible for
      differential energy storage and metabolic responses between these populations.
      This work demonstrates the metabolic versatility of the nine-spined stickleback
      and the pertinence of an energetic framework to better understand potential local
      adaptations. It also demonstrates that instead of using a single acclimation
      temperature thermal reaction norms should be compared when studying individuals
      originating from different thermal environments in a common garden setting.

PMID- 25389080
TI  - Psoriasis in the elderly: epidemiological and clinical aspects, and evaluation of
      patients with very late onset psoriasis.
AB  - BACKGROUND: Age of the patients and age of onset of psoriasis may have an impact
      on the disease. There is little information about psoriasis in elderly patients.
      OBJECTIVE: We evaluated epidemiological, clinical aspects, comorbidities and
      treatments of psoriasis in the elderly (>70 years) patients, and in patients with
      very late onset psoriasis (onset >= 70 years). METHODS: This observational
      multicentre non-interventional study of adults with psoriasis was conducted in 29
      departments of dermatology in France. A total of 2210 adults with psoriasis were
      included. RESULTS: A total of 212 (9.5%) patients were elderly. This group had a
      higher frequency of females (P = 0.005), a later onset of the disease (P <
      0.0001), a lower frequency of familial (P < 0.0001) and plaque psoriasis (P <
      0.0001), but higher frequency of guttate and inverse psoriasis (P <= 0.005).
      Hypertension, diabetes, dyslipidaemia, and major cardiovascular events (MACE)
      were more frequent in this group (P < 0.0001), but not tobacco (P < 0.0001).
      Systemic and biological therapies were used less frequently in the elderly group
      (P < 0.0001). Fifty-eight (2.7%) patients had late onset psoriasis. Patients with
      very late onset psoriasis were more frequently women (P = 0.02) and older (P <
      0.0001), among elderly group. They had significantly less frequently familial (P
      < 0.0001) and plaque psoriasis (P < 0.0001), and were less often on systemic
      treatment including biological. Frequencies of comorbidities were not statically
      different but patients with 'early' onset psoriasis have a tendency (P < 0.5) to
      have higher frequencies of obesity, diabetes, dyslipidaemia, hypertension and
      MACE. CONCLUSION: This study highlights phenotypic features of psoriasis in
      elderly and in very late onset psoriasis. The management of these fragile
      patients remains poorly codified and needs further investigation.

PMID- 25389081
TI  - Development of systemic sclerosis in patients with Behcet's disease: remission of
      Behcet's disease in parallel with the progression of skin sclerosis.

PMID- 25389082
TI  - Tetracycline tethered to titanium inhibits colonization by Gram-negative
      bacteria.
AB  - As peri-prosthetic infection is one of the most devastating complications
      associated with implant placement, we have reasoned that such infection can be
      largely subverted by development of antibacterial implants. Our previous work
      demonstrated that covalent coupling of vancomycin to titanium alloy prevented
      colonization by the Gram-positive pathogens, Staphylococcus aureus and
      Staphylococcus epidermidis. Some orthopedic devices, including permanent
      prosthesis anchors, and most dental implants are transcutaneous or transmucosal
      and can be prone to colonization by Gram-negative pathogens. We report here the
      successful covalent coupling of the broad-spectrum antibiotic, tetracycline
      (TET), to titanium surfaces (Ti-TET) to retard Gram-negative colonization.
      Synthetic progress was followed by changes in water contact angle, while the
      presence of TET was confirmed by immunofluorescence. Ti-TET actively prevented
      colonization in the presence of bathing Escherichia coli, both by fluorescence
      microscopy and direct counting. Finally, the Ti-TET surface supported
      osteoblastic cell adhesion and proliferation over a 72-h period. Thus, this new
      surface offers a powerful means to protect transcutaneous implants from adhesion
      of Gram-negative pathogens, decreasing the need for replacement of this hardware.

PMID- 25389083
TI  - ABO incompatible renal transplantation without antibody removal using
      conventional immunosuppression alone.
AB  - ABO incompatible living donor renal transplantation (ABOi) can achieve outcomes
      comparable to ABO compatible transplantation (ABOc). However, with the exception
      of blood group A2 kidneys transplanted into recipients with low titer anti-A
      antibody, regimens generally include antibody removal, intensified
      immunosuppression and splenectomy or rituximab. We now report a series of 20
      successful renal transplants across a range of blood group incompatibilities
      using conventional immunosuppression alone in recipients with low baseline anti
      blood group antibody (ABGAb) titers. Incompatibilities were A1 to O (3), A1 to B
      (2), A2 to O (2), AB to A (2), AB to B (1), B to A1 (9), B to O (1); titers 1:1
      to 1:16 by Ortho. At 36 months, patient and graft survival are 100%. Antibody
      mediated rejection (AbMR) occurred in one patient with thrombophilia and low
      level donor-specific anti-HLA antibody. Four patients experienced cellular
      rejection (two subclinical), which responded to oral prednisolone. This series
      demonstrates that selected patients with low titer ABGAb can undergo ABOi with
      standard immunosuppression alone, suggesting baseline titer as a reliable
      predictor of AbMR. This reduces morbidity and cost of ABOi for patients with low
      titer ABGAb and increases the possibility of ABOi from deceased donors. 

PMID- 25389084
TI  - Inducible cell labeling and lineage tracking during fracture repair.
AB  - Mouse models incorporating inducible Cre-ERT2/LoxP recombination coupled with
      sensitive fluorescent reporter lines are being increasingly used to track cell
      lineages in vivo. In this study we use two inducible reporter strains, Ai9iCol2a1
      (Ai9*Col2a1-creERT2) to track contribution of chondrogenic progenitors during
      bone regeneration in a closed fracture model and Ai9i UBC (Ai9*UBC-creERT2) to
      examine methods for inducing localized recombination. By comparing with Ai9
      littermate controls as well as inducible reporter mice not dosed with tamoxifen,
      we revealed significant leakiness of the CreERT2 system, particularly in the bone
      marrow of both lines. These studies highlight the challenges associated with
      highly sensitive reporters that may be activated without induction in tissues
      where the CreERT2 fusion is expressed. Examination of the growth plate in the
      Ai9iCol2a1 strain showed cells of the osteochondral lineage (cell co-staining
      with chondrocyte and osteoblast markers) labeled with the tdTom reporter.
      However, no such labeling was noted in healing fractures of Ai9iCol2a1 mice.
      Attempts to label a single limb using intramuscular injection of 4
      hydroxytamoxifen in the Ai9i UBC strain resulted in complete labeling of the
      entire animal, comparable to intraperitoneal injection. While a challenge to
      interpret, these data are nonetheless informative regarding the limitations of
      these inducible reporter models, and justify caution and expansive controls in
      future studies using such models.

PMID- 25389085
TI  - Role of the intestinal microbiota and fecal transplantation in inflammatory bowel
      diseases.
AB  - Ulcerative colitis and Crohn's disease are the two major types of inflammatory
      bowel disease (IBD). Despite intensive study, it is still challenging because the
      precise etiology and pathogenesis remains unclear. Studies have shown that IBD is
      associated with changes in the composition of intestinal microbiota, as either a
      cause or a consequence of abnormal host immune response in genetic susceptible
      population. Two specific microorganisms (Mycobacterium avium subsp.
      paratuberculosis and Escherichia coli) get more widely studied, but till now no
      single microorganism has been identified as the only pathogen. Genetic
      susceptibility data also suggest impaired handling of bacteria as well as an
      improper immune response to potential pathogens. The microbiota provides new
      therapeutic methods, and fecal microbiota transplantation may restore the balance
      of intestinal flora to supplement or optimize the current therapies. 

PMID- 25389086
TI  - Small RNA profiles from virus-infected fresh market vegetables.
AB  - Functional small RNAs, such as short interfering RNAs (siRNAs) and microRNAs
      (miRNAs), exist in freshly consumed fruits and vegetables. These siRNAs can be
      derived either from endogenous sequences or from viruses that infect them.
      Symptomatic tomatoes, watermelons, zucchini, and onions were purchased from
      grocery stores and investigated by small RNA sequencing. By aligning the obtained
      small RNA sequences to sequences of known viruses, four different viruses were
      identified as infecting these fruits and vegetables. Many of these virally
      derived small RNAs along with endogenous small RNAs were found to be highly
      complementary to human genes. However, the established history of safe
      consumption of these vegetables suggests that this sequence homology has little
      biological relevance. By extension, these results provide evidence for the safe
      use by humans and animals of genetically engineered crops using RNA-based
      suppression technologies, especially vegetable crops with virus resistance
      conferred by expression of siRNAs or miRNAs derived from viral sequences. 

PMID- 25389087
TI  - Smokers come to accept plain cigarette packaging, Australian study shows.

PMID- 25389088
TI  - SNP rs7770370 in HLA-DPB1 loci as a major genetic determinant of response to
      booster hepatitis B vaccination: results of a genome-wide association study.
AB  - BACKGROUND AND AIM: Hepatitis B (HB) vaccination is highly effective in reducing
      the risk of hepatitis B virus infection. However, breakthrough and chronic
      hepatitis B virus infections in vaccinated subjects raised concern about its long
      term efficacy. The specific aim of the study was to explore the host genetic
      determinants of long-term immunological memory against HB vaccination. METHODS:
      We conducted a case-control study nested in a cohort of HB booster recipients who
      had received primary HB vaccination during infancy but failed to reside an anti
      HBs titers >= 10 mIU/mL at the age of 15-18 years. We used a genome-wide single
      nucleotide polymorphism (SNP) array plate to scan autosomal chromosomes and
      assayed the human leukocyte antigen (HLA)-DPB1 genotype by sequence-based
      techniques. RESULTS: We found that 10 of the 112 candidate SNPs (P-value < 5.0 *
      10(-5) ) clustered within a 47-Kb region of the HLA-DP loci. All the minor
      alleles of these HLA-DP candidate SNPs were correlated with lower likelihoods of
      nonresponse to HB vaccine. There was a significant linkage disequilibrium between
      these HLA-DP candidate SNPs and HLA-DPB1 protective alleles. Multivariate
      analyses showed that rs7770370 was the most significant genetic factor. As
      compared with rs7770370 GG homozygotes, adjusted odds ratios were 0.524 (95%
      confidence interval, 0.276-0.993) and 0.095 (95% confidence interval, 0.030
      0.307) for AG heterozygotes and AA homozygotes, respectively. CONCLUSION: Our
      results showed that rs7770370 was the most significant genetic factor of response
      to HB booster. The rs7770370 and nearby SNPs may also contribute to the long-term
      immunological memory against HB vaccination.

PMID- 25389089
TI  - [Testicular malignit tumors - are we in the end of the road?].
AB  - Testicular germ cell tumors are currently the most curable cancer in adults. The
      5-year survival is 95 %. In spite of this many patients come to physician in
      advanced stage of disease. The early diagnosis is an only way to improve outcomes
      in accordance to standardization, successfulness of complex diagnostic and
      therapy algorithm. Misdiag-nosis and errors of physicians are very rare nowadays
      however knowledge and oncology awareness of our young male population is
      inadequate. Health education targeted at young male population at risk has up to
      day large reserves.Key words: cisplatin - germ cell tumors - incidence -
      mortality - NSGCT - prevalence - seminoma. 

PMID- 25389090
TI  - [Patient follow-up after treatment of breast, colorectal and prostate cancer].
AB  - The prevalence of malignant tumors (not including non-melanoma skin cancer) in
      the Czech Republic exceeds 350,000 persons, including patients with active
      disease and those with a history of malignancy. A substantial portion of this
      population are in long-term complete remission after cancer treatment. These
      patients are at high risk of cancer recurrence and long-term complications
      associated with previous cancer therapy. The aim of this review is to summarize
      current follow-up recommendations for the three most common solid tumor types,
      including breast, colorectal, and prostate cancer.Key words: breast cancer -
      colorectal cancer - follow-up - prevalence - prostate cancer. 

PMID- 25389091
TI  - [Differential diagnostics of hypereosinophilia].
AB  - Hypereosinophilia is characterized by chronic increase of peripheral blood
      eosinophiles with common damage to vari-ous organs due to eosinophilic
      infiltration and release of mediators. Hypereosinophilia should be both reactive
      and clonal, and accompanies group of heterogeneous disorders (infectious,
      pulmonary, immunologic, malignant). Based on recent advances in molecular and
      genetic diagnostic techniques and increasing experience with differences in
      clinical features and prognosis, some subtypes of clonal hypereosinophilic
      syndromes have been defined, such as myeloproliferative variants, including
      chronic eosinophilic leukemia, and lymphocytic variants, but other subtypes
      remain undefined. Differential diagnostics oh hypereosinophilie therefore remains
      one of very important medical issues.Key words: differential diagnostics -
      hypereosinophilia. 

PMID- 25389092
TI  - [Development and current utility of infobases in Czech cancer care].
AB  - Evaluation of the quality and effectiveness of health care is an integral part of
      modern health care. It can only be performed with sufficiently detailed data
      sources describing each segment of care. In case of significant heterogeneity and
      lack of standardization of hospital information systems it is necessary to fully
      exploit existing parametric data sources. The valid systems for Czech cancer
      care: the National Cancer Registry, clinical registries of Czech Society for
      Oncology of the Czech Medical Association of J.E. Purkyne, registries of
      screening programs and administrative data form healthcare payers. From these
      registries we can obtain a very complex and detailed view on prevention,
      diagnosis and cancer treatment in the Czech Republic. To achieve this goal, which
      means more integrated and comprehensive utilization of national registries,
      surveys and administrative data, it is necessary to fully utilize and apply the
      current legislative framework, in particular provision of the Act no. 372/2011
      Sb.Key words: clinical registry - evaluation of health care - information system 
      legislation - malignant tumor - population. 

PMID- 25389093
TI  - [About pain - otherwise].
AB  - We can speak about palliative medicine from different points of view. Twelve
      years in hospice care and my clinical, health policy and foreign experiences have
      ensured me that our medical service is one of the best in the world.
      Unfortunately, it is not completely balanced to acute care and does not have
      ability to reflect the needs of chronically ill patients. These patients are now
      the vast majority of aging population and the topics as (not only) geriatric
      fragility and palliative care will rise interest in daily clinical practice, in
      decision making process, in health policy and in economy in the coming 20 years.
      In this environment, we, the doctors, are the key indicators of quality, because
      our personality and decisions fundamentally affect the plan of care. The question
      is whether we know the real needs of patients, whether we look not only for
      medical but also for general human resources to achieve them, and whether the
      current system and society allow this. This reflection is about these rather
      philosophical and moral aspects of our work and about role of doctor in "modern
      times". KEYWORDS: aging population - geriatric fragility syndrome - health policy
      - palliative care - socio-economic aspects of care.

PMID- 25389094
TI  - [New antibiotics: do we need new molecules or new strategies?].
AB  - Even though the situation in the field of research and development of new
      antimicrobial agents is not ideal, the years of stagnation, especially among anti
      gramnegative agents, seem to be over. During the years 2011-2012 we have
      witnessed a movement towards a development of some new antibiotic agents not only
      with anti-gramposi-tive activity but with anti-gramnegative too, as well as new
      antituberculotics and antifungals. Here we present some of these new
      antiinfectives, presented in conferences during the last year, of which many are
      being shifted to the level of clinical trials of phase II-III, while others are
      in stage of preclinical studies. KEYWORDS: antibiotics - antimycotics -
      antituberculotics.

PMID- 25389095
TI  - [Geriatric patient in oncology].
AB  - At the beginning of the article there are mentioned the stages of human life
      breakdown and breakdown of senior age by stages approximately corresponding to
      functional efficiency. Attention is paid to a specific geriatric regime
      respecting the differences of senior age. Article emphasizes the role of
      comprehensive geriatric assessment including evaluation of psychological changes
      and social aspects in accordance to optimal geriatric approach. Diagnostic
      strategy and oncology treatment in terms of prognosis and expected goals are also
      described. There are discussed the specifics of diseases in elderly patients in
      the cancer context. Present work reviews the differences between ca-lendar and
      biological age with possibility to segregate seniors and to avoid inadequate
      palliative care. Finally, the author discusses the aspects of supportive care for
      seniors and polypharmacotherapy with its potential risk. KEYWORDS: functional
      geriatric examination - palliative care - polypharmacotherapy - specific
      geriatric regime - supportive care - specifics of diseases in elderly patients.

PMID- 25389096
TI  - [New aspects of impact of papillomavirus status in the therapy of head/neck
      cancer].
AB  - The human papillomavirus (HPV) has been identified as the causative agent of a
      growing subset of head and neck squamous cell carcinomas. The HPV status of the
      tumors provides prognostic information and may direct treatment strategies. The
      new and somewhat surprising results presented this years will have an important
      impact on the treatment of HPV positive head and neck cancers.Key words:
      cetuximab - head and neck cancer - human papillomavirus - oropharyngeal cancer. 

PMID- 25389097
TI  - [Ph-negative myeloproliferative diseases with thrombocythemia in the context of
      Thromboreductin(r) treatment, data from registry 2013].
AB  - Czech Working Group for Ph-negative Myeloproliferative diseases (CZEMP)
      recommends anagrelid (Thromboreductin(r)) for the treatment of Ph-negative
      chronic myeloproliferative disease (MPO) with thrombocythemia accompanying. To
      evaluate the efficacy of this treatment, the patient registry with essential
      thrombocythemia and/or thrombocytosis accompanying other Ph-negative
      myeloproliferative diseases was established. The beginnings of data collection go
      back to 2001, registry itself is maintained from 2005 and the aim is to archive
      the medical records with detailed physical and laboratory examination, safety
      patient profile included. The longest follow-up monitors 150 months period.
      Registry database contained 1,325 patients in the end of 2013, with an annual
      increase of anagrelid therapy as a drug of first choice in accordance with CZEMP
      guidelines approved by the Czech Society of Hematology of Czech Medical
      Association of J. E. Purkyne. Indication criteria contribute to this trend as
      anagrelid is the first choice agent in 65 years old patients, instead previous 60
      years of age. Often, we can observe the combined treatment, especially, in older
      patients and in patients with primary myelofibrosis and polycythemia vera. There
      have been founded 543 thrombotic events in 413 patients and 63 bleeding events in
      58 patients of study group by the end of 2013. During treatment, thrombosis was
      diagnosed 225 times in 171 patients and bleeding was observed 139 times in 104
      patients. The therapeutic response is achieved after 3 months in 77% and after 6
      months in 83% of subjects, but after 12 months, the treatment still fails in
      12,5% of patients. It might be caused by slow titration of Thromboreductin(r).
      One of the most important indicators of treatment success is the effect on
      clinical symptoms presentation, especially the occurrence of thrombotic events.
      The proof of a good treatment efficacy is demonstrated by 1.8 fold decrease in
      arterial thrombosis, more than 1.5 fold decrease in microvascular thrombosis and
      even 6.2 fold decrease in venous thromboembolism events. Bleeding is observed in
      about double more patients in comparison to the period before inclusion in the
      systematic monitoring, but the bleedings are clinically insignificant.Key words:
      anagrelid (Thromboreductin(r)) - Ph-myeloproliferative diseases - registry -
      thrombosis. 

PMID- 25389098
TI  - [Diabetes mellitus and malignancies].
AB  - The epidemiological studies have proven an increased incidence of cancer in
      patients with diabetes and the ne-gative effect of diabetes on their prognosis.
      The relation to type 2 diabetes was found in hepatic, pancreatic and endometrial
      malignancies, in colorectal, breast and bladder cancers. Diabetes as well as
      malignancies are multifactorial diseases with a number of common risk factors:
      age, gender, race, overweight and obesity, diet, physical activity. A higher
      incidence of malignancies in diabetic patients is not only a result of sharing
      these risk factors, as diabetes itself predisposes to carcinoma development.
      Possible mechanisms producing this effect include hyperinsulinemia,
      hyperglycemia, oxidative stress, chronic inflammation, obesity related factors
      and effect of diabetic complications. The development of malignancies in
      diabetics is also affected by the diabetes treatment. Exogenous insulin and its
      analogues and stimulators of insulin secretion are linked to an increased risk of
      cancer while insulin sensitizers to its decrease. Special attention is given to
      metformin which, apart from the indirect effect by influencing the levels of
      insulin and glycemia, has a direct anticancerogenic effect. In the clinical
      practice, it is ne-cessary to give attention to the screening of diabetes related
      tumours, consistent glycemic control and choice of appropriate diabetes treatment
      in patients with a high cancer risk.Key words: clinical practice - diabetes
      mellitus - effects of diabetes treatment - malignancies. 

PMID- 25389099
TI  - [Palliative medicine and the "good death"].
AB  - Palliative care can improve the quality of life in terminally ill patients and
      allow them to achieve a "good death". Active assessment and proactive
      interventions on all levels of patient's suffering is of major importance. The
      articel proposes a theoretical model of the "good death" and brings practical
      recommendations for the implementation of palliative care into routine clinical
      practice.Key words: good death - palliative medicine - quality of life - terminal
      phase. 

PMID- 25389100
TI  - [Clinical evaluation of new drugs against orphan diseases in oncology - the
      current situation in Europe and in our country].
AB  - Cancer represents one of the main causes of death among diseases across the age
      spectrum. Tumors in children, however, represent less than 1% of the total number
      of cancers in the population and in terms of the definition of orphan diseases in
      Europe are all children's cancers considered as orphan diseases. This is the
      reason why the research and development of new agents against cancer in childhood
      stands outside of the main interest. Every year around 30,000 new cases of cancer
      in children and adolescents are diagnosed in the European Unioun (EU) and
      approximately 80% of them achieve long-term remission using mainly conventional
      methods of treatment. However, almost 6,000 children and adolescents die every
      year of malignant tumors therefore cancer remains a major cause of morbidity and
      mortality. Consequently, there is a demand for new and safe drugs for children
      suffering from cancer which would lead to improved survival and to risk reduction
      of late adverse effects of cancer treatment. In the past 10 years in the EU, more
      in the EU-15 than in our country, 20 performed oncology trials in phase I
      involving adults account for only one trial in pediatric patients. The issue of
      new drugs clinical testing in rare cancers is very complex, complicated and for
      current unsatisfactory situation might be responsible various aspects. These
      aspects contain the legislative field, the problem of determining the correct
      dose of testing drug as a single agent or in combination therapy, the use of
      testing drug in advanced disease or already in de novo diagnosed patients, as
      well as equity (equal) access to new drugs being tested, the goal set for each
      molecule/drug in clinical trials, the conflict of interest balanced with
      sufficient professionalism and last but not least, the need for new methodologies
      and statistical approaches. The aim of this article is to describe the issue
      complexity of incorporation of new, modern drug for cancer patients with orphan
      diseases, including children.Key words: clinical evaluation - new drugs - orphan
      diseases in oncology. 

PMID- 25389101
TI  - [Palliative care and chronic heart failure].
AB  - Heart failure is a very common clinical syndrome in cardiology which reduces life
      expectancy and has a significant impact on the quality of life. The treatment of
      heart failure improves survival thus the number of patients who reach the
      terminal state increases with this diagnosis. Major symptoms and psychosocial
      difficulties begin to appear during therapy which aims to prolong life or cure
      the life limiting illnesses. The World Health Organization (WHO) changed its
      definition in 2002 and concluded that palliative care should be provided "in the
      early stages of disease, together with another treatment that prolongs life."
      Palliative care involves multiple disciplines in order to solve problems caused
      by the symptoms of the disease and other related aspects of the patient and
      family who are considered as a one subject, because a feeling of well-being has
      an impact on others.Key words: heart failure - non-pharmacological treatment -
      palliative care. 

PMID- 25389102
TI  - Contact system activation on endothelial cells.
AB  - When the contact system assembles and activates on negatively charged surface
      materials, plasma coagulation rapidly follows. This mechanism is redundant for
      hemostasis but mediates pathological thrombus formation, as was reported in a
      multitude of in vivo studies. The epidemiological data are presently scarce to
      firmly support a role for the contact system in human thrombotic disease, while
      its physiological function and mode of activation remains mysterious. Besides its
      role in blood coagulation in vitro, the contact system is responsible for the
      production of bradykinin. This inflammatory peptide is involved in episodes of
      pathological tissue swelling in (hereditary) angioedema, but potentially also in
      the physiological regulation of vascular permeability. A body of evidence
      indicates that contact system factors are recruited to the surface of activated
      endothelial cells, where proteins that are locally released can activate them.
      Furthermore, clinical and biochemical studies indicate that plasmin, the effector
      enzyme of the fibrinolytic system, can evoke contact system activation. This
      auxiliary role for plasmin may so far not have been fully appreciated in
      pathophysiology. To conclude this review, we propose a complementary model for
      contact system activation on the endothelial cell surface that is initiated by
      plasmin activity. 

PMID- 25389103
TI  - The paradox of the lupus anticoagulant: history and perspectives.
AB  - A unique coagulation inhibitor prolonging whole-blood clotting time was described
      more than 50 years ago in two patients with systemic lupus erythematosus (SLE).
      The immunoglobulin nature of the inhibitor and its interaction with
      antiphospholipid antibodies was later demonstrated and the term "lupus
      anticoagulant (LA)" was coined to describe this laboratory finding. It soon
      became apparent that LA was a misnomer as it is often found in plasma from
      patients with clinical conditions other than SLE and is associated with
      thromboembolic events that may occur in otherwise healthy individuals.
      Individuals with LA have circulating autoantibodies that inhibits blood
      coagulation. These are mostly of IgG or IgM class and mainly directed against a
      phospholipid (PL)-binding plasma protein, beta2-glycoprotein I (beta2GPI). The
      presence of beta2GPI-dependent LA represents a well-recognized risk factor for
      venous and arterial thromboembolism, as well as pregnancy loss and morbidity.
      beta2GPI-dependent LA in the presence of documented previous thromboembolism, or
      history of pregnancy loss/morbidity, identifies definite anti-PL syndrome.
      Laboratory diagnosis of LA is thus of particular importance, as it may assign
      patients with a common event (thrombosis) to a group with a high risk for
      recurrence, which is a prerequisite for long-term oral antithrombotic treatment. 

PMID- 25389104
TI  - Evolutionary obstetrics.

PMID- 25389106
TI  - Electrophysiological and antiarrhythmic properties of potassium canrenoate during
      myocardial ischemia-reperfusion.
AB  - INTRODUCTION: Recent clinical studies have reported the potential benefit of an
      early mineralocorticoid receptor (MR) blockade with potassium canrenoate (PC) on
      ventricular arrhythmias (VAs) occurrence in patients experiencing an ST-segment
      elevation myocardial infarction (STEMI). However, most of the
      electrophysiological properties of PC demonstrated to date have been investigated
      in normoxic conditions, and therefore, in vitro experiments during an acute
      myocardial ischemia-reperfusion were lacking. MATERIALS AND METHODS: We used
      rabbit in vitro models and standard microelectrode technique to assess the
      electrophysiological impact of PC during myocardial ischemia-reperfusion,
      including right ventricle mimicking the "border zone" existing between normal and
      ischemic/reperfused areas (1 umol/L, 10 and 100 nmol/L), isolated right
      ventricle, and sinoatrial node (SAN) experiments (1 umol/L, respectively).
      RESULTS: During ischemia-reperfusion, acute superfusion of PC 100 nmol/L
      prevented the increase in action potential (AP) duration at 90% of repolarization
      (APD90) dispersion between ischemic and nonischemic areas and in VAs occurrence
      induced by aldosterone 10 nmol/L (86 +/- 3 vs 114 +/- 4 milliseconds for
      aldosterone alone, P < .05). Potassium canrenoate also induced conduction blocks
      and significantly decreased Vmax during simulated ischemia (from 25 +/- 5 to 12
      +/- 4, 14 +/- 3, and 14 +/- 5 V/s, respectively, for PC 1 umol/L, 100, and 10
      nmol/L, P < .05). Potassium canrenoate 1 umol/L demonstrated cycle length (CL)
      dependent effects on APD90 and on Vmax, and it also reduced SAN beating CL (from
      446 +/- 28 to 529 +/- 24 millisecond, P < .05). CONCLUSION: Our experimental
      study highlights new evidence for an antiarrhythmic impact of PC during
      myocardial ischemia-reperfusion via multiple channels modulation. These results
      are in line with recent clinical trials suggesting that an early MR blockade in
      STEMI may be preventive of VAs.

PMID- 25389105
TI  - Modern reproductive patterns associated with estrogen receptor positive but not
      negative breast cancer susceptibility.
AB  - It has long been accepted that modern reproductive patterns are likely
      contributors to breast cancer susceptibility because of their influence on
      hormones such as estrogen and the importance of these hormones in breast cancer.
      We conducted a meta-analysis to assess whether this 'evolutionary mismatch
      hypothesis' can explain susceptibility to both estrogen receptor positive (ER
      positive) and estrogen receptor negative (ER-negative) cancer. Our meta-analysis
      includes a total of 33 studies and examines parity, age of first birth and age of
      menarche broken down by estrogen receptor status. We found that modern
      reproductive patterns are more closely linked to ER-positive than ER-negative
      breast cancer. Thus, the evolutionary mismatch hypothesis for breast cancer can
      account for ER-positive breast cancer susceptibility but not ER-negative breast
      cancer. 

PMID- 25389108
TI  - Boron as a powerful reductant: synthesis of a stable boron-centered radical-anion
      radical-cation pair.
AB  - Despite the fundamental importance of radical-anion radical-cation pairs in
      single-electron transfer (SET) reactions, such species are still very rare and
      transient in nature. Since diborenes have highly electron-rich B?B double bonds,
      which makes them strong neutral reductants, we envisaged a possible realization
      of a boron-centered radical-anion radical-cation pair by SET from a diborene to a
      borole species, which are known to form stable radical anions upon one-electron
      reduction. However, since the reduction potentials of all know diborenes (E1/2 =
      1.05/-1.55 V) were not sufficiently negative to reduce MesBC4 Ph4 (E1/2 =-1.69
      V), a suitable diborene, IiPr?(iPr)B?B(iPr)?IiPr, was tailor-made to comply with
      these requirements. With a halfwave potential of E1/2 =-1.95 V, this diborene
      ranks amongst the most powerful neutral organic reductants known and readily
      reacted with MesBC4 Ph4 by SET to afford a stable boron-centered radical-anion
      radical-cation pair. 

PMID- 25389107
TI  - Advanced cancer as a risk for major depressive episodes.
AB  - OBJECTIVE: Major depression adversely affects health communication, quality of
      life, and survival in patients with advanced cancer. Prior research provides
      limited insight into how patients with advanced cancer differ from the general
      population in risk for developing a major depressive episode (MDE). This study
      aims to determine whether advanced cancer poses distinct risks for initial and
      recurrent MDEs. METHODS: Advanced cancer patients (N = 628) from Coping with
      Cancer were compared with propensity-weighted general population controls (N =
      9282) from the National Comorbidity Survey Replication. RESULTS: Patients with
      advanced cancer were more likely than comparisons to have an initial MDE [OR =
      27.3, 95% CI = (14.8-50.4); p < 0.001] but no more likely than comparisons to
      have a recurrent MDE [OR = 1.5, 95% CI = (0.9-2.6); p = 0.160]. Nearly two thirds
      (64.4%) of current MDEs in patients were initial onset; the vast majority (91.8%)
      of current MDEs in comparisons were recurrent. CONCLUSIONS: Advanced cancer
      increases risk of an initial MDE but appears not to enhance risk of a recurrent
      MDE. This suggests the importance of screening widely for depression in patients
      with advanced cancer as opposed to targeting screening to presumably high-risk
      subgroups of those with psychiatric histories.

PMID- 25389109
TI  - Inclusive fitness and sexual conflict: how population structure can modulate the
      battle of the sexes.
AB  - Competition over reproductive opportunities among members of one sex often harms
      the opposite sex, creating a conflict of interest between individual males and
      females. Recently, this battle of the sexes has become a paradigm in the study of
      intersexual coevolution. Here, we review recent theoretical and empirical
      advances suggesting that - as in any scenario of intraspecific competition -
      selfishness (competitiveness) can be influenced by the genetic relatedness of
      competitors. When competitors are positively related (e.g. siblings), an
      individual may refrain from harming its competitor(s) and their mate(s) because
      this can improve the focal individual's inclusive fitness. These findings reveal
      that population genetic structure might be of paramount importance when studying
      the battle of the sexes. We conclude by identifying some new lines of research at
      the interface of sexual selection and social evolution. 

PMID- 25389110
TI  - Multiferroicity of carbon-based charge-transfer magnets.
AB  - A new type of carbon charge-transfer magnet, consisting of a fullerene acceptor
      and single-walled carbon nanotube donor, is demonstrated, which exhibits room
      temperature ferromagnetism and magnetoelectric (ME) coupling. In addition,
      external stimuli (electric/magnetic/elastic field) and the concentration of a
      nanocarbon complex enable the tunabilities of the magnetization and ME coupling
      due to the control of the charge transfer. 

PMID- 25389111
TI  - Functional adaptations of the bacterial chaperone trigger factor to extreme
      environmental temperatures.
AB  - Trigger factor (TF) is the first molecular chaperone interacting
      cotranslationally with virtually all nascent polypeptides synthesized by the
      ribosome in bacteria. Thermal adaptation of chaperone function was investigated
      in TFs from the Antarctic psychrophile Pseudoalteromonas haloplanktis, the
      mesophile Escherichia coli and the hyperthermophile Thermotoga maritima. This
      series covers nearly all temperatures encountered by bacteria. Although
      structurally homologous, these TFs display strikingly distinct properties that
      are related to the bacterial environmental temperature. The hyperthermophilic TF
      strongly binds model proteins during their folding and protects them from heat
      induced misfolding and aggregation. It decreases the folding rate and counteracts
      the fast folding rate imposed by high temperature. It also functions as a carrier
      of partially folded proteins for delivery to downstream chaperones ensuring final
      maturation. By contrast, the psychrophilic TF displays weak chaperone activities,
      showing that these functions are less important in cold conditions because
      protein folding, misfolding and aggregation are slowed down at low temperature.
      It efficiently catalyses prolyl isomerization at low temperature as a result of
      its increased cellular concentration rather than from an improved activity. Some
      chaperone properties of the mesophilic TF possibly reflect its function as a cold
      shock protein in E. coli. 

PMID- 25389112
TI  - DNA methyltransferase 1 drives transcriptional down-modulation of beta catenin
      antagonist Chibby1 associated with the BCR-ABL1 gene of chronic myeloid leukemia.
AB  - The decrease of Chibby1 (CBY1) contributes to beta catenin constitutive
      activation associated with the presence of the BCR-ABL1 fusion gene of chronic
      myeloid leukemia (CML). This is mediated by transcriptional events and driven by
      DNA hyper-methylation at promoter-associated CpG islands of the CBY1-encoding
      gene C22orf2. Moreover, CBY1 transcriptional induction proceeding from promoter
      de-methylation is a component of BCR-ABL1+ cell response to Imatinib (IM). Our
      study showed that DNA methyltransferase 1 (DNMT1) has a central role in the hyper
      methylation at the C22orf2 promoter. Further investigation in leukemic
      hematopoietic progenitors from IM-responsive and IM-resistant CML patients at
      diagnosis failed to demonstrate any correlation between DNMT1-driven hyper
      methylation of the C22orf2 promoter and response to IM. Notably, the response to
      IM was neither predicted by DNMT1-driven hyper-methylation of BCL2-like11 at
      diagnosis. In conclusion, the hypermethylation of C22orf2 and BCL2-like11
      promoters proceeding from DNMT1 is a crucial component of their reduced
      expression, but it is not directly involved in CML resistance to IM. It might
      rather contribute to the disease evolution towards a drug-resistant phenotype in
      more advanced phases or blast crisis.

PMID- 25389114
TI  - Validation of a coding algorithm to identify bladder cancer and distinguish stage
      in an electronic medical records database.
AB  - Studies on outcomes in bladder cancer rely on accurate methods to identify
      patients with bladder cancer and differentiate bladder cancer stage. Medical
      record and administrative databases are increasingly used to study cancer
      incidence, but few have distinguished cancer stage, and none have focused on
      bladder cancer. In this study, we used data from The UK Health Improvement
      Network (THIN) to identify patients with bladder cancer using at least one
      diagnostic code for bladder cancer, and distinguish muscle-invasive from non
      invasive disease using a subsequent code for cystectomy. Algorithms were
      validated against a gold standard of physician-completed questionnaires,
      pathology reports, and consultant letters. Algorithm performance was evaluated by
      measuring positive predictive value (PPV) and corresponding 95% confidence
      interval (CI). Among all patients coded with bladder cancer (n = 194), PPV for
      any bladder cancer was 99.5% (95% CI, 97.2-99.9). PPV for incident bladder cancer
      was 93.8% (95% CI, 89.4-96.7). PPV for muscle-invasive bladder cancer was 70.1%
      (95% CI, 59.4-79.5) in patients with cystectomy (n = 95) and 83.9% (95% CI, 66.3
      94.5) in those with cystectomy plus additional codes for metastases and death (n
      = 31). Using our codes for bladder cancer, the age- and sex-standardized
      incidence rate (SIR) of bladder cancer in THIN approximated that measured by
      cancer registries (SIR within 20%), suggesting that sensitivity was high as well.
      THIN is a valid and novel database for the study of bladder cancer. Our algorithm
      can be used to examine the epidemiology of muscle-invasive bladder cancer or
      outcomes following cystectomy for patients with muscle invasion.

PMID- 25389115
TI  - Genotype-defined cancer risk in juvenile polyposis syndrome.
AB  - BACKGROUND: Germline mutations in SMAD4 and BMPR1A disrupt the transforming
      growth factor beta signal transduction pathway, and are associated with juvenile
      polyposis syndrome. The effect of genotype on the pattern of disease in this
      syndrome is unknown. This study evaluated the differential impact of SMAD4 and
      BMPR1A gene mutations on cancer risk and oncological phenotype in patients with
      juvenile polyposis syndrome. METHODS: Patients with juvenile polyposis syndrome
      and germline SMAD4 or BMPR1A mutations were identified from a prospectively
      maintained institutional registry. Medical records were reviewed and the clinical
      patterns of disease were analysed. RESULTS: Thirty-five patients had germline
      mutations in either BMPR1A (8 patients) or SMAD4 (27). Median follow-up was 11
      years. Colonic phenotype was similar between patients with SMAD4 and BMPR1A
      mutations, whereas SMAD4 mutations were associated with larger polyp numbers
      (number of patients with 50 or more gastric polyps: 14 versus 0 respectively).
      The numbers of patients with rectal polyps was comparable between BMPR1A and
      SMAD4 mutation carriers (5 versus 17). No patient was diagnosed with cancer in
      the BMPR1A group, whereas four men with a SMAD4 mutation developed
      gastrointestinal (3) or extraintestinal (1) cancer. The gastrointestinal cancer
      risk in patients with juvenile polyposis syndrome and a SMAD4 mutation was 11 per
      cent (3 of 27). CONCLUSION: The SMAD4 genotype is associated with a more
      aggressive upper gastrointestinal malignancy risk in juvenile polyposis syndrome.

PMID- 25389116
TI  - Predatory publishing.

PMID- 25389117
TI  - Cymbopogon citratus industrial waste as a potential source of bioactive
      compounds.
AB  - BACKGROUND: Cymbopogon citratus (Cc), commonly known as lemongrass, is a very
      important crop worldwide, being grown in tropical countries. It is widely used in
      the food, pharmaceutical, cosmetic and perfumery industries for its essential
      oil. Cc aqueous extracts are also used in traditional medicine. They contain high
      levels of polyphenols, which are known for their antioxidant and anti
      inflammatory properties. Hydrodistillation of lemongrass essential oil produces
      an aqueous waste (CcHD) which is discarded. Therefore a comparative study between
      CcHD and Cc infusion (CcI) was performed to characterize its phytochemical
      profile and to research its antioxidant and anti-inflammatory potential. RESULTS:
      HPLC-PDA/ESI-MS(n) analysis showed that CcI and CcHD have similar phenolic
      profiles, with CcHD presenting a higher amount of polyphenols. Additionally, both
      CcI and CcHD showed antioxidant activity against DPPH (EC50 of 41.72 +/- 0.05 and
      42.29 +/- 0.05 ug mL(-1) respectively) and strong anti-inflammatory properties,
      by reducing NO production and iNOS expression in macrophages and through their NO
      scavenging activity, in a dose-dependent manner. Furthermore, no cytotoxicity was
      observed. CONCLUSION: The data of this study encourage considering the aqueous
      solution from Cc leaf hydrodistillation as a source of bioactive compounds, which
      may add great industrial value to this crop.

PMID- 25389118
TI  - Elucidation of substituted ester group position in octenylsuccinic anhydride
      modified sugary maize soluble starch.
AB  - The octenylsuccinic groups in esterification-modified sugary maize soluble
      starches with a low (0.0191) or high (0.0504) degree of substitution (DS) were
      investigated by amyloglucosidase hydrolysis followed by a combination of chemical
      and physical analysis. The results showed the zeta-potential remained at
      approximately the same value regardless of excessive hydrolysis. The weight
      average molecular weight decreased rapidly and reached 1.22 * 10(7) and 1.60 *
      10(7) g/mol after 120 min for low-DS and high-DS octenylsuccinic anhydride (OSA)
      modified starch, respectively. The pattern of z-average radius of gyration as
      well as particle size change was similar to that of Mw, and z-average radius of
      gyration decreased much more slowly, especially for high-DS OSA starch. Compared
      to native starch, two characteristic absorption peaks at 1726.76 and 1571.83 cm(
      1) were observed in FT-IR spectra, and the intensity of absorption peaks
      increased with increasing DS. The NMR results showed that OSA starch had several
      additional peaks at 0.8-3.0 ppm and a shoulder at 5.56 ppm for OSA substituents,
      which were grafted at O-2 and O-3 positions in soluble starch. The even
      distribution of OSA groups in the center area of soluble starch particle has been
      directly shown under CLSM. Most substitutions were located near branching points
      of soluble starch particles for a low-DS modified starch, whereas the substituted
      ester groups were located near branching points as well as at the nonreducing
      ends in OSA starch with a high DS. 

PMID- 25389119
TI  - 2014 JRR Terashima Award.

PMID- 25389121
TI  - Development of the curve of Spee in Class II subdivision malocclusion: a
      longitudinal study.
AB  - OBJECTIVE: To compare the depth of curve of Spee (COS) in Class I and II sides of
      Class II subdivision malocclusion longitudinally and to describe the changes in
      the COS in relation to dental arch over time. MATERIALS AND METHOD: The study
      group comprised 17 subjects exhibiting Class II subdivision malocclusion. The
      depth of COS, intermolar width, distances from mesial anatomic contact points of
      the first permanent molars to the contact point of the central incisors in Class
      I and II sides and arch length in mandible were analysed on digital models in
      three different time points based on cervical vertebral maturation (T1; mean age:
      12.4 years, T2; mean age: 15.1 years, and T3: mean age: 19.1 years). Pearson's
      correlation coefficients were calculated and linear multiple regression analysis
      with enter method was carried out. RESULTS: No significant differences were found
      in the depth of COS between Class I and II sides in all time periods. The
      mesiobuccal cusp of the first molar was the deepest part of COS in both sides and
      in all time periods, with a maximum depth of 2.37+/-0.83mm in T1 and a minimum
      depth of 1.91+/-0.66mm in T3. Between baseline and final follow-up; the depth of
      COS, ach length, and distance in Class I side decreased significantly. Arch
      length had a significant correlation with the depth of COS (r = 0.471) in T3.
      CONCLUSIONS: As the depth of COS did not differ between either the Class II or I
      sides, the same mechanics can be used to level the COS in either sides of the
      mandibular arch.

PMID- 25389120
TI  - Effect of a national primary care pay for performance scheme on emergency
      hospital admissions for ambulatory care sensitive conditions: controlled
      longitudinal study.
AB  - OBJECTIVE: To estimate the impact of a national primary care pay for performance
      scheme, the Quality and Outcomes Framework in England, on emergency hospital
      admissions for ambulatory care sensitive conditions (ACSCs). DESIGN: Controlled
      longitudinal study. SETTING: English National Health Service between 1998/99 and
      2010/11. PARTICIPANTS: Populations registered with each of 6975 family practices
      in England. MAIN OUTCOME MEASURES: Year specific differences between trend
      adjusted emergency hospital admission rates for incentivised ACSCs before and
      after the introduction of the Quality and Outcomes Framework scheme and two
      comparators: non-incentivised ACSCs and non-ACSCs. RESULTS: Incentivised ACSC
      admissions showed a relative reduction of 2.7% (95% confidence interval 1.6% to
      3.8%) in the first year of the Quality and Outcomes Framework compared with ACSCs
      that were not incentivised. This increased to a relative reduction of 8.0% (6.9%
      to 9.1%) in 2010/11. Compared with conditions that are not regarded as being
      influenced by the quality of ambulatory care (non-ACSCs), incentivised ACSCs also
      showed a relative reduction in rates of emergency admissions of 2.8% (2.0% to
      3.6%) in the first year increasing to 10.9% (10.1% to 11.7%) by 2010/11.
      CONCLUSIONS: The introduction of a major national pay for performance scheme for
      primary care in England was associated with a decrease in emergency admissions
      for incentivised conditions compared with conditions that were not incentivised.
      Contemporaneous health service changes seem unlikely to have caused the sharp
      change in the trajectory of incentivised ACSC admissions immediately after the
      introduction of the Quality and Outcomes Framework. The decrease seems larger
      than would be expected from the changes in the process measures that were
      incentivised, suggesting that the pay for performance scheme may have had impacts
      on quality of care beyond the directly incentivised activities.

PMID- 25389122
TI  - MicroRNA-29b inhibits migration and proliferation of vascular smooth muscle cells
      in neointimal formation.
AB  - The proliferation and migration of smooth muscle cells (SMCs) are considered to
      be key steps in the progression of atherosclerosis and restenosis. Certain
      stimuli, such as, interleukin-3 (IL-3) are known to stimulate proliferation and
      migration in vascular diseases. Meanwhile, microRNAs (miRs) have been revealed as
      critical modulators of various diseases in which miR-29b is known to regulate
      cell growth by targeting Mcl-1 and MMP2. However, roles of miR-29b in vascular
      smooth muscle cells remain almost unknown. We hypothesized that miR-29b may
      control the proliferation and migration processes induced by IL-3 stimulation by
      inhibiting its own specific targets in SMCs. MiR-29b significantly suppressed the
      proliferation and migration of SMCs through the inhibition of the signaling
      pathway related to Mcl-1 and MMP2. We also found that miR-29b expression levels
      significantly declined in balloon-injured rat carotid arteries and that the
      overexpression of miR-29b by local oligonucleotide delivery can inhibit
      neointimal formation. Consistent with the critical role of miR-29b in vitro, we
      observed down-regulated expression levels of Mcl-1 and MMP2 from the neointimal
      region. These results indicate that miR-29b suppressed the proliferation and
      migration of SMCs, possibly through the inhibition of Mcl-1 and MMP2, and suggest
      that miR-29b may serve as a useful therapeutic tool to treat cardiovascular
      diseases such as, atherosclerosis and restenosis.

PMID- 25389124
TI  - Effect of coloured shade-nets on plant leaf parameters and tomato fruit quality.
AB  - BACKGROUND: The concept of photo-selective netting using commercial cultivation
      practices was studied in a tomato (Solanum lycopersicum 'Vedetta') summer
      cultivation in south Serbia (under high solar radiation 910 W m(-2) , with a
      photosynthetic photon flux density of 1661 umol m(-2) s(-1) ), under four
      different coloured shade-nets (pearl, red, blue and black) with 40% relative
      shading. The aim of the study was to determine how different environmental
      control technologies (coloured shade-nets as screen house or plastic-house
      integrated with coloured shade-nets) could influence plant parameters, production
      and quality traits in tomato fruits cultivated in south Serbia (Balkan region).
      RESULTS: The leaf area index (LAI) ranged from 4.6 to 5.8 in open field and
      plastic tunnels plants (control) with maximum LAI values of 7.9-8.2 in net houses
      with red colour nets. Shade-grown leaves generally have higher total chlorophyll
      and carotenoids content than do control leaves. Pericarp thickness was
      significantly higher tomatoes grown under pearl (7.215.82 um), red (7099.00 um)
      and blue nets (6802.29 um) compared to other treatments and to control (6202.48
      um). The highest concentration of lycopene was detected in tomatoes grown in
      plastic houses integrated with red colour nets (64.9 ug g(-1) fresh weight). The
      plastic house and open field (control) tomato production had a taste index mean
      value of 1.09-1.10. This is significantly higher than the values determined for
      the treatments with different coloured shade-nets. CONCLUSION: These results show
      that red and pearl photo-selective nets create optimal growing conditions for the
      growth of the plant and produce fruits with thicker pericarp, the highest
      lycopene content, a satisfactory level of taste index and can be further
      implemented within protected cultivation practices.

PMID- 25389123
TI  - Dissecting Neural Responses to Temporal Prediction, Attention, and Memory:
      Effects of Reward Learning and Interoception on Time Perception.
AB  - Temporal prediction (TP) is needed to anticipate future events and is essential
      for survival. Our sense of time is modulated by emotional and interoceptive
      (corporal) states that are hypothesized to rely on a dopamine (DA)-modulated
      "internal clock" in the basal ganglia. However, the neurobiological substrates
      for TP in the human brain have not been identified. We tested the hypothesis that
      TP involves DA striato-cortical pathways, and that accurate responses are
      reinforcing in themselves and activate the nucleus accumbens (NAc). Functional
      magnetic resonance imaging revealed the involvement of the NAc and anterior
      insula in the temporal precision of the responses, and of the ventral tegmental
      area in error processing. Moreover, NAc showed higher activation for successful
      than for unsuccessful trials, indicating that accurate TP per se is rewarding.
      Inasmuch as activation of the NAc is associated with drug-induced addictive
      behaviors, its activation by accurate TP could help explain why video games that
      rely on TP can trigger compulsive behaviors. 

PMID- 25389125
TI  - Breastfeeding and delivery room neonatal collapse.
AB  - Sudden unexpected neonatal collapse in the delivery room is a rare occurrence in
      healthy term infants. Upper airway obstruction may occur from improper
      positioning of the newborn even while breastfeeding. Such occlusion may have dire
      consequences if not recognized immediately. We report 2 healthy term neonates who
      suffered respiratory arrest while in the mother's arms and attempting
      breastfeeding. In each case, rapid response by the delivery room nurse averted
      tragedy. Metabolic and infectious evaluations were unremarkable. Both babies have
      been well on subsequent examinations. We conclude that proper education of
      mothers and safe positioning of neonates is critical during the initiation of
      breastfeeding. 

PMID- 25389126
TI  - Military milk: breastfeeding rates among Australian Defence Force women who
      return to military service following maternity leave.
AB  - BACKGROUND: The breastfeeding behaviors among Australian Defence Force women have
      not previously been examined. Studies have shown that breastfeeding prevalence
      and duration are affected by maternity leave entitlements and returning to work.
      OBJECTIVES: This study aimed to benchmark breastfeeding initiation, prevalence,
      and duration among a cohort of Australian Defence Force women and to compare
      these findings against Australian population norms. METHODS: A cross-sectional
      survey was conducted via email in 2008 for Australian Defence Force women who had
      taken maternity leave in the Australian financial year of 2006/2007. Analysis of
      breastfeeding indicators was undertaken. RESULTS: Ninety-eight percent of
      Australian Defence Force women in this cohort initiated breastfeeding and
      breastfed for a median duration of 8 months, returning to work when the mean age
      of the child was 8.4 months. Breastfeeding prevalence did not meet 2003
      Australian National Health and Medical Research Council targets by 6 months
      postpartum but compared favorably to the Australian population norms. Sixty-six
      percent of the respondents returned to work full-time, with a median
      breastfeeding duration of 7 months. Women who returned to work part-time had a
      longer median duration of 10 months. CONCLUSION: Breastfeeding rates among this
      cohort of Australian Defence Force women compare favorably with the general
      Australian population until 9 months, coinciding with returning to work after a
      period of maternity leave. The results support recent Australian population
      studies on breastfeeding and employment.

PMID- 25389127
TI  - Breast milk pumping beliefs, supports, and barriers on a university campus.
AB  - BACKGROUND: Compared to nonemployed mothers, employed mothers are more likely to
      terminate breastfeeding sooner than recommended, due in part to a lack of
      workplace support. OBJECTIVE: The purpose of this study is to compare the beliefs
      of employees and students affiliated with a university regarding pumping breast
      milk on campus. METHODS: This qualitative study used semistructured interviews
      grounded in the theory of planned behavior, focused on behavioral, normative, and
      control beliefs regarding pumping on campus. Responses were independently coded
      and categorized based on common themes. Response frequencies were calculated and
      compared between students, staff, and faculty. RESULTS: Thirty-two women (11
      students, 8 staff, 13 faculty) participated in the interview. Overall,
      participants most frequently reported that maintaining milk supply/extending
      breastfeeding duration was an advantage to pumping on campus, and time/scheduling
      issues a disadvantage. The most commonly perceived supporters were peers, whereas
      those unaware, uninformed, and/or disapproving of breastfeeding were most
      commonly perceived as opponents to pumping on campus. Reporting within each
      category differed between students, staff, and faculty. It is notable that
      students most frequently identified the lack of available pumping space as a
      barrier, whereas faculty often reported that space availability made pumping on
      campus easier for them. In addition, both staff and faculty frequently stated
      that scheduling and time constraints were a pumping barrier. CONCLUSION: An
      inequality of current lactation support practice may exist at colleges and
      universities. It is necessary to extend this protection to all members of a
      workplace, regardless of their role.

PMID- 25389128
TI  - Birth and breastfeeding dynamics in a modernizing indigenous community.
AB  - BACKGROUND: Changes in health care access and birthing practices may pose
      barriers to optimal breastfeeding in modernizing rural populations. OBJECTIVES:
      We evaluated temporal and maternal age-related trends in birth and breastfeeding
      in a modernizing Maya agriculturalist community. We tested 2 hypotheses: (1) home
      births would be associated with better breastfeeding outcomes than hospital
      births, and (2) vaginal births would be associated with better breastfeeding
      outcomes than cesarean births. METHODS: We interviewed 58 Maya mothers (ages 21
      85) regarding their births and breastfeeding practices. General linear models
      were used to evaluate trends in birthing practices and breastfeeding outcomes
      (timing of breastfeeding initiation, use of infant formula, age of introduction
      of complementary feeding, and breastfeeding duration). We then compared
      breastfeeding outcomes by location (home or hospital) and mode of birth (vaginal
      or cesarean). RESULTS: Timing of breastfeeding initiation and the rate of formula
      feeding both increased significantly over time. Younger mothers introduced
      complementary foods earlier, breastfed for shorter durations, and formula fed
      more than older mothers. Vaginal hospital births were associated with earlier
      breastfeeding initiation and longer breastfeeding durations than home births.
      Cesarean births were associated with later breastfeeding initiation, shorter
      breastfeeding durations, and more formula feeding than vaginal hospital births.
      CONCLUSION: We have observed temporal and maternal age-related trends toward
      suboptimal breastfeeding patterns in the Maya community. Contrary to our first
      hypothesis, hospital births per se were not associated with negative
      breastfeeding outcomes. In support of our second hypothesis, cesarean versus
      vaginal births were associated with negative breastfeeding outcomes.

PMID- 25389129
TI  - Sucrose induces vesicle accumulation and autophagy.
AB  - It has been shown that the treatment of mammalian cells with sucrose leads to
      vacuole accumulation associated with lysosomes and upregulation of lysosomal
      enzyme expression and activity. Autophagy is an evolutionarily conserved
      homeostatic process by which cells deliver cytoplasmic material for degradation
      into lysosomes, thus it is probable that sucrose affects the autophagic activity.
      The role of sucrose in autophagy is unknown; however, another disaccharide,
      trehalose has been shown to induce autophagy. In the current study, we used mouse
      embryonic fibroblasts to investigate whether sucrose induces autophagy and
      whether vesicle formation is associated with autophagy. The results showed that
      sucrose induces autophagy while being accumulated within the endosomes/lysosomes.
      These vesicles were swollen and packed within the cytoplasm. Furthermore,
      trehalose and the trisaccharide raffinose, which are not hydrolyzed in mammalian
      cells, increased the rate of vesicles accumulation and LC3-II level (a protein
      marker of autophagy). However, fructose and maltose did not show the same
      effects. The correlation between the two processes, vesicle accumulation and
      autophagy induction, was confirmed by treatment of cells with sucrose plus
      invertase, or maltose plus acarbose-the alpha-glucosidase inhibitor-and by
      sucrose deprivation. Results also showed that vesicle accumulation was not
      affected by autophagy inhibition. Therefore, the data suggest that sucrose
      induced autophagy through accumulation of sucrose-containing vesicles is caused
      by the absence of hydrolysis enzymes.

PMID- 25389130
TI  - An unusual cecal mass on routine colonoscopy.
AB  - Cecal masses secondary to extra-luminal compression are rare. We report a case of
      a 72-year-old man with a cecal mass found during routine colonoscopy with
      multiple biopsies showing normal colonic mucosa. The patient had a relevant past
      surgical history of a bilateral open inguinal hernia repair using the 'Plug-and
      Patch' mesh system. A computed tomography scan of the abdomen and pelvis showed a
      4 * 3.3 cm mass that compressed the wall of the cecum. A neoplastic process could
      not be ruled out. Diagnostic laparoscopy with intraoperative colonoscopy showed
      that the right hernia plug was not deployed and was causing extrinsic compression
      of the anterior cecal wall and an intraluminal impression upon insufflation of
      the colon. This case report reiterates the importance of combining intraoperative
      colonoscopy with laparoscopy for diagnosis of undetermined colonic masses. 

PMID- 25389131
TI  - A case of pyogenic liver abscesses in a previously healthy adolescent man.
AB  - An 18-year-old, previously healthy man admitted with abdominal pain, high-grade
      fevers, nausea and emesis was found to have multiple hepatic abscesses.
      Aspiration cultures grew Fusobacterium necrophorum, a rare bacterium causing
      potentially fatal liver abscesses in humans. Following sequential percutaneous
      drainages and narrowing of antibiotics, the patient was discharged on a 6-week
      antibiotic course and showed no signs of infection. A week after presentation it
      was discovered that he had experienced upper respiratory symptoms and sore throat
      prior to presentation. Because oropharyngeal infections are a potential source of
      bacteremia, they must be considered in the differential diagnosis of patients
      presenting with hepatic abscesses and no evidence of immunocompromise. 

PMID- 25389132
TI  - Visualization of the heterogeneous membrane distribution of sphingomyelin
      associated with cytokinesis, cell polarity, and sphingolipidosis.
AB  - Sphingomyelin (SM) is a major sphingolipid in mammalian cells and is reported to
      form specific lipid domains together with cholesterol. However, methods to
      examine the membrane distribution of SM are limited. We demonstrated in model
      membranes that fluorescent protein conjugates of 2 specific SM-binding toxins,
      lysenin (Lys) and equinatoxin II (EqtII), recognize different membrane
      distributions of SM; Lys exclusively binds clustered SM, whereas EqtII
      preferentially binds dispersed SM. Freeze-fracture immunoelectron microscopy
      showed that clustered but not dispersed SM formed lipid domains on the cell
      surface. Glycolipids and the membrane concentration of SM affect the SM
      distribution pattern on the plasma membrane. Using derivatives of Lys and EqtII
      as SM distribution-sensitive probes, we revealed the exclusive accumulation of SM
      clusters in the midbody at the time of cytokinesis. Interestingly, apical
      membranes of differentiated epithelial cells exhibited dispersed SM distribution,
      whereas SM was clustered in basolateral membranes. Clustered but not dispersed SM
      was absent from the cell surface of acid sphingomyelinase-deficient Niemann-Pick
      type A cells. These data suggest that both the SM content and membrane
      distribution are crucial for pathophysiological events bringing therapeutic
      perspective in the role of SM membrane distribution.

PMID- 25389133
TI  - Retinoic acid receptor signaling is required to maintain glucose-stimulated
      insulin secretion and beta-cell mass.
AB  - Retinoic acid signaling is required for maintaining a range of cellular
      processes, including cell differentiation, proliferation, and apoptosis. We
      investigated the actions of all-trans-retinoic acid (atRA) signaling in
      pancreatic beta-cells of adult mice. atRA signaling was ablated in beta-cells by
      overexpressing a dominant-negative retinoic acid receptor (RAR)-alpha mutant
      (RARdn) using an inducible Cre-Lox system under the control of the pancreas
      duodenal homeobox gene promoter. Our studies establish that hypomorphism for RAR
      in beta-cells leads to an age-dependent decrease in plasma insulin in the fed
      state and in response to a glucose challenge. Glucose-stimulated insulin
      secretion was also impaired in islets isolated from mice expressing RARdn. Among
      genes that are atRA responsive, Glut2 and Gck mRNA levels were decreased in
      isolated islets from RARdn-expressing mice. Histologic analyses of RARdn
      expressing pancreata revealed a decrease in beta-cell mass and insulin per beta
      cell 1 mo after induction of the RARdn. Our results indicate that atRA signaling
      mediated by RARs is required in the adult pancreas for maintaining both beta-cell
      function and mass, and provide insights into molecular mechanisms underlying
      these actions.

PMID- 25389134
TI  - Genetic ablation of N-linked glycosylation reveals two key folding pathways for
      R345W fibulin-3, a secreted protein associated with retinal degeneration.
AB  - An R345W mutation in the N-glycoprotein, fibulin-3 (F3), results in inefficient
      F3 folding/secretion and higher intracellular F3 levels. Inheritance of this
      mutation causes the retinal dystrophy malattia leventinese. N-Linked
      glycosylation is a common cotranslational protein modification that can regulate
      protein folding efficiency and energetics. Therefore, we explored how N
      glycosylation alters the protein homeostasis or proteostasis of wild-type (WT)
      and R345W F3 in ARPE-19 cells. Enzymatic and lectin binding assays confirmed that
      WT and R345W F3 are both primarily N-glycosylated at Asn249. Tunicamycin
      treatment selectively reduced R345W F3 secretion by 87% (vs. WT F3). Genetic
      elimination of F3 N-glycosylation (via an N249Q mutation) caused R345W F3 to
      aggregate intracellularly and adopt an altered secreted conformation. The
      endoplasmic reticulum (ER) chaperones GRP78 (glucose-regulated protein 78) and
      GRP94 (glucose-regulated protein 94), and the ER lectins calnexin and
      calreticulin were identified as F3 binding partners by immunoprecipitation.
      Significantly more N249Q and N249Q/R345W F3 interacted with GRP94, while
      substantially less N249Q and N249Q/R345W interacted with the ER lectins than
      their N-glycosylated counterparts. Inhibition of GRP94 ATPase activity reduced
      only N249Q/R345W F3 secretion (by 62%), demonstrating this variant's unique
      reliance on GRP94 for secretion. These observations suggest that R345W F3, but
      not WT F3, requires N-glycosylation to acquire a stable, native-like structure.

PMID- 25389135
TI  - Inadequate mental healthcare in immigration removal centres.

PMID- 25389137
TI  - Nebulised hypertonic saline in bronchiolitis: take it with a pinch of salt.

PMID- 25389136
TI  - Understanding high and low patient experience scores in primary care: analysis of
      patients' survey data for general practices and individual doctors.
AB  - OBJECTIVES: To determine the extent to which practice level scores mask variation
      in individual performance between doctors within a practice. DESIGN: Analysis of
      postal survey of patients' experience of face-to-face consultations with
      individual general practitioners in a stratified quota sample of primary care
      practices. SETTING: Twenty five English general practices, selected to include a
      range of practice scores on doctor-patient communication items in the English
      national GP Patient Survey. PARTICIPANTS: 7721 of 15,172 patients (response rate
      50.9%) who consulted with 105 general practitioners in 25 practices between
      October 2011 and June 2013. MAIN OUTCOME MEASURE: Score on doctor-patient
      communication items from post-consultation surveys of patients for each
      participating general practitioner. The amount of variance in each of six
      outcomes that was attributable to the practices, to the doctors, and to the
      patients and other residual sources of variation was calculated using
      hierarchical linear models. RESULTS: After control for differences in patients'
      age, sex, ethnicity, and health status, the proportion of variance in
      communication scores that was due to differences between doctors (6.4%) was
      considerably more than that due to practices (1.8%). The findings also suggest
      that higher performing practices usually contain only higher performing doctors.
      However, lower performing practices may contain doctors with a wide range of
      communication scores. CONCLUSIONS: Aggregating patients' ratings of doctors'
      communication skills at practice level can mask considerable variation in the
      performance of individual doctors, particularly in lower performing practices.
      Practice level surveys may be better used to "screen" for concerns about
      performance that require an individual level survey. Higher scoring practices are
      unlikely to include lower scoring doctors. However, lower scoring practices
      require further investigation at the level of the individual doctor to
      distinguish higher and lower scoring general practitioners.

PMID- 25389138
TI  - The International Depression Epidemiological Study (TIDES): unfinished business?

PMID- 25389141
TI  - Umbilical blood flow patterns directly after birth before delayed cord clamping.
AB  - BACKGROUND: Delayed umbilical cord clamping (DCC) affects the cardiopulmonary
      transition and blood volume in neonates immediately after birth. However, little
      is known of blood flow in the umbilical vessels immediately after birth during
      DCC. The objective is to describe the duration and patterns of blood flow through
      the umbilical vessels during DCC. METHODS: Arterial and venous umbilical blood
      flow was measured during DCC using Doppler ultrasound in uncomplicated term
      vaginal deliveries. Immediately after birth, the probe was placed in the middle
      of the umbilical cord, pattern and duration of flow in vein and arteries were
      evaluated until cord clamping. RESULTS: Thirty infants were studied. Venous flow:
      In 10% no flow was present, in 57% flow stopped at 4:34 (3:03-7:31) (median (IQR)
      min:sec) after birth, before the cord was clamped. In 33%, flow continued until
      cord clamping at 5:13 (2:56-9:15) min:sec. Initially, venous flow was
      intermittent, increasing markedly during large breaths or stopping and reversing
      during crying, but then became continuous. Arterial flow: In 17% no flow was
      present, in 40% flow stopped at 4:22 (2:29-7:17) min:sec, while cord pulsations
      were still palpable. In 43% flow continued until the cord was clamped at 5:16
      (3:32-10:10) min:sec. Arterial flow was pulsatile, unidirectional towards
      placenta or bidirectional to/from placenta. In 40% flow became continuous towards
      placenta later on. CONCLUSIONS: During delayed umbilical cord clamping, venous
      and arterial umbilical flow occurs for longer than previously described. Net
      placental transfusion is probably the result of several factors of which
      breathing could play a major role. Umbilical flow is unrelated to cessation of
      pulsations.

PMID- 25389139
TI  - SABRE: a multicentre randomised control trial of nebulised hypertonic saline in
      infants hospitalised with acute bronchiolitis.
AB  - AIM: Acute bronchiolitis is the commonest cause for hospitalisation in infancy.
      Supportive care remains the cornerstone of current management and no other
      therapy has been shown to influence the course of the disease. It has been
      suggested that adding nebulised hypertonic saline to usual care may shorten the
      duration of hospitalisation. To determine whether hypertonic saline does have
      beneficial effects we undertook an open, multi-centre parallel-group, pragmatic
      RCT in ten UK hospitals. METHODS: Infants admitted to hospital with a clinical
      diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to
      receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6
      hourly. Randomisation was within 4 h of admission. The primary outcome was time
      to being assessed as 'fit' for discharge with secondary outcomes including time
      to discharge, incidence of adverse events together with follow up to 28 days
      assessing patient centred health related outcomes. RESULTS: A total of 317
      infants were recruited to the study. 158 infants were randomised to HS (141
      analysed) and 159 to standard care (149 analysed). There was no difference
      between the two arms in time to being declared fit for discharge (hazard ratio: 0
      95, 95% CI: 0.75-1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76
      1.23). There was no difference in adverse events. One infant in the HS group
      developed bradycardia with desaturation. CONCLUSION: This study does not support
      the use of nebulised HS in the treatment of acute bronchiolitis over usual care
      with minimal handlings. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT01469845.

PMID- 25389142
TI  - Accounting for multiple births in randomised trials: a systematic review.
AB  - OBJECTIVES: Multiple births are an important subgroup to consider in trials aimed
      at reducing preterm birth or its consequences. Including multiples results in a
      unique mixture of independent and clustered data, which has implications for the
      design, analysis and reporting of the trial. We aimed to determine how multiple
      births were taken into account in the design and analysis of recent trials
      involving preterm infants, and whether key information relevant to multiple
      births was reported. DESIGN: We conducted a systematic review of multicentre
      randomised trials involving preterm infants published between 2008 and 2013.
      Information relevant to multiple births was extracted. RESULTS: Of the 56 trials
      included in the review, 6 (11%) excluded multiples and 24 (43%) failed to
      indicate whether multiples were included. Among the 26 trials that reported
      multiples were included, only one (4%) accounted for clustering in the sample
      size calculations and eight (31%) took the clustering into account in the
      analysis of the primary outcome. Of the 20 trials that randomised infants, 12
      (60%) failed to report how infants from the same birth were randomised.
      CONCLUSIONS: Information on multiple births is often poorly reported in trials
      involving preterm infants, and clustering due to multiple births is rarely taken
      into account. Since ignoring clustering could result in inappropriate
      recommendations for clinical practice, clustering should be taken into account in
      the design and analysis of future neonatal and perinatal trials including infants
      from a multiple birth.

PMID- 25389144
TI  - Google glass in surgery.

PMID- 25389143
TI  - Anticoagulant therapy during primary percutaneous coronary intervention for acute
      myocardial infarction: a meta-analysis of randomized trials in the era of stents
      and P2Y12 inhibitors.
AB  - OBJECTIVES: To investigate the relative benefits of unfractionated heparin, low
      molecular weight heparin(LMWH), fondaparinux, and bivalirudin as treatment
      options for patients with ST segment elevation myocardial infarction undergoing
      percutaneous coronary intervention (PCI). DESIGN: Mixed treatment comparison and
      direct comparison meta-analysis of randomized trials in the era of stents and
      P2Y12 inhibitors. DATA SOURCES AND STUDY SELECTION: A search of Medline, Embase,
      Cochrane Central Register of Controlled Trials (CENTRAL) for randomized trials
      comparing unfractionated heparin plus glycoprotein IIb/IIIa inhibitor(GpIIb/IIIa
      inhibitor), unfractionated heparin, bivalirudin, fondaparinux, or LMWH plus
      GpIIb/IIIa inhibitor for patients undergoing primary PCI. OUTCOMES: The primary
      efficacy outcome was short term (in hospital or within 30 days) major adverse
      cardiovascular event; the primary safety outcome was short term major bleeding.
      RESULTS: We identified 22 randomized trials that enrolled 22,434 patients. In the
      mixed treatment comparison models, when compared with unfractionated heparin plus
      GpIIb/IIIa inhibitor, unfractionated heparin was associated with a higher risk of
      major adverse cardiovascular events (relative risk 1.49 (95% confidence interval
      1.21 to 1.84), as were bivalirudin (relative risk 1.34 (1.01 to 1.78)) and
      fondaparinux (1.78 (1.01 to 3.14)). LMWH plus GpIIb/IIIa inhibitor showed highest
      treatment efficacy, followed (in order) by unfractionated heparin plus GpIIb/IIIa
      inhibitor, bivalirudin, unfractionated heparin, and fondaparinux. Bivalirudin was
      associated with lower major bleeding risk compared with unfractionated heparin
      plus GpIIb/IIIa inhibitor (relative risk 0.47 (0.30 to 0.74)) or unfractionated
      heparin (0.58 (0.37 to 0.90)). Bivalirudin, followed by unfractionated heparin,
      LMWH plus GpIIb/IIIa inhibitor, unfractionated heparin plus GpIIb/IIIa inhibitor,
      and fondaparinux were the hierarchy for treatment safety. Results were similar in
      direct comparison meta-analyses: bivalirudin was associated with a 39%, 44%, and
      65% higher risk of myocardial infarction, urgent revascularization, and stent
      thrombosis respectively when compared with unfractionated heparin with or without
      GpIIb/IIIa inhibitor. However, bivalirudin was associated with a 48% lower risk
      of major bleeding compared with unfractionated heparin plus GpIIb/IIIa inhibitor
      and 32% lower compared with unfractionated heparin alone. CONCLUSIONS: In
      patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor
      and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of
      major adverse cardiovascular events, whereas bivalirudin was safest, with the
      lowest bleeding. These relationships should be considered in selecting
      anticoagulant therapies in patients undergoing primary PCI.

PMID- 25389145
TI  - Experiences in adoption of teledermatology in Mohs micrographic surgery: using
      smartglasses for intraoperative consultation and defect triage.

PMID- 25389147
TI  - Characterization of Sporohalobacter salinus sp. nov., an anaerobic, halophilic,
      fermentative bacterium isolated from a hypersaline lake.
AB  - Halophilic, obligately anaerobic, Gram-stain-negative bacterial strains were
      isolated from a sediment sample taken from under the salt crust of El-Jerid
      hypersaline lake in southern Tunisia by using tryptone or glucose as the
      substrate. One strain, CEJFT1B(T), was characterized phenotypically and
      phylogenetically. Cells were non-motile, non-spore-forming, short rods. Strain
      CEJFT1B(T) was able to grow in the presence of 5-30 % (w/v) NaCl (optimum 20 %)
      and at 30-60  degrees C (optimum 45  degrees C). It grew at pH 5.5-7.8 and the
      optimum pH for growth was 6.8. The isolate required yeast extract for growth.
      Substrates utilized by strain CEJFT1B(T) as the sole carbon source included
      glucose, fructose, sucrose, pyruvate, Casamino acids and starch. Individual amino
      acids such as glutamate, lysine, methionine, serine, tyrosine, and amino acid
      mixtures formed by the Stickland reaction such as alanine-glycine, valine
      proline, leucine-proline, isoleucine-proline were also utilized. Products of
      glucose fermentation were acetate (major product), butyrate, H2 and CO2. The
      genomic DNA G+C content of strain CEJFT1B(T) was 32.3 mol%. Phylogenetic analysis
      based on 16S rRNA gene sequences indicated that strain CEJFT1B(T) should be
      assigned to the genus Sporohalobacter. The sequence similarity between strain
      CEJFT1B(T) and Sporohalobacter lortetii was 98.5 %, but DNA-DNA hybridization
      between the two strains revealed a relatedness value of 56.4 %, indicating that
      they are not related at the species level. The combination of phylogenetic
      analysis, DNA-DNA hybridization data, and differences in substrate utilization
      support the view that strain CEJFT1B(T) represents a novel species of the genus
      Sporohalobacter, for which the name Sporohalobacter salinus sp. nov. is proposed.
      The type strain is CEJFT1B(T) ( = DSM 26781(T) = JCM 19279(T)).

PMID- 25389146
TI  - Biological dose response to PM2.5: effect of particle extraction method on
      platelet and lung responses.
AB  - Particulate matter (PM) exposure contributes to respiratory diseases and
      cardiopulmonary mortality. PM toxicity is related to sources and composition,
      such as abundance of polycyclic aromatic hydrocarbons (PAHs). We exposed adult
      male BALB/c mice, via oropharyngeal aspiration, to a range of doses of PM2.5
      collected during the winter in downtown Sacramento near a major freeway
      interchange (SacPM). Two preparation methods (spin-down and multi-solvent
      extraction) were tested to remove particles from collection filters. Three doses
      were analyzed 24 h after treatment for (1) leukocytes and total protein in
      bronchoalveolar lavage fluid (BALF), (2) airway-specific and whole lobe
      expression of PAH-sensitive genes (CYP1B1 and CYP1A1) and IL-1 b, (3) lung
      histology, and (4) platelet function. Both extraction methods stimulated
      biological responses, but the spin-down method was more robust at producing IL-1
      b and CYP1B1 gene responses and the multi-solvent extraction induced whole lung
      CYP1A1. Neutrophils in the BALF were increased 5- to 10-fold at the mid and high
      dose for both preparations. Histopathology scores indicated dose-dependent
      responses and increased pathology associated with spin-down-derived PM exposure.
      In microdissected airways, spin-down PM increased CYP1B1 gene expression
      significantly, but multi-solvent extracted PM did not. Platelet responses to the
      physiological agonist thrombin were approximately twice as potent in the spin
      down preparation as in the multi-solvent extract. We conclude (1) the method of
      filter extraction can influence the degree of biological response, (2) for SacPM
      the minimal effective dose is 27.5-50 ug based on neutrophil recruitment, and (3)
      P450s are upregulated differently in airways and lung parenchyma in response to
      PAH-containing PM.

PMID- 25389148
TI  - Description of Pseudobacteriovorax antillogorgiicola gen. nov., sp. nov., a
      bacterium isolated from the gorgonian octocoral Antillogorgia elisabethae,
      belonging to the family Pseudobacteriovoracaceae fam. nov., within the order
      Bdellovibrionales.
AB  - A bacterial strain designated RKEM611(T) was isolated from the octocoral
      Antillogorgia elisabethae, collected off the coast of San Salvador, The Bahamas.
      The strain is Gram-stain-negative, an obligate aerobe, and pleomorphic. It
      requires NaCl for growth and exhibits optimal growth at 1-2 % (w/v) NaCl, 30-37 
      degrees C and pH 6.0-8.0. The predominant cellular fatty acids are C16 : 1omega5c
      and C16 : 0; the major respiratory quinone is menaquinone MK-6, and the DNA G+C
      content is 46.3 mol%. Based on phylogenetic analysis of the 16S rRNA gene, in
      addition to phenotypic characteristics, RKEM611(T) represents a novel species and
      genus of a novel family within the order Bdellovibrionales. The names
      Pseudobacteriovoracaceae fam. nov. and Pseudobacteriovorax antillogorgiicola
      gen., nov., sp., nov. are proposed. Isolate RKEM611(T) ( = NCCB 100521(T) = LMG
      28452(T)) is the type strain.

PMID- 25389149
TI  - Rhizobacter bergeniae sp. nov., isolated from the root of Bergenia scopulosa.
AB  - A yellowish-pigmented bacterium, designated strain PLGR-1(T), was isolated from
      the root of Bergenia scopulosa collected from Taibai Mountain in Shaanxi
      Province, north-west China, and was subjected to a taxonomic study by using a
      polyphasic approach. Cells of strain PLGR-1(T) were Gram-stain-negative, strictly
      aerobic, rod-shaped, non-spore-forming and motile with a single polar flagellum.
      Growth occurred at 7-33  degrees C (optimum, 25-28  degrees C), at pH 5.0-10.0
      (optimum, pH 6.0-7.0) and with 0-0.5 % (w/v) NaCl (optimum, 0 %). The predominant
      respiratory quinone was ubiquinone-8 (Q-8) and the major cellular fatty acids
      were summed feature 3 (comprising C16 : 1omega7c and/or C16 : 1omega6c), C16 : 0
      and summed feature 8 (comprising C18 : 1omega7c and/or C18 : 1omega6c). The major
      polyamines were putrescine and 2-hydroxyputrescine and the major polar lipids
      were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol.
      The DNA G+C content was 69.8 mol%. Phylogenetic analyses based on 16S rRNA gene
      sequences showed that strain PLGR-1(T) belonged to the class Betaproteobacteria
      and formed a tight phyletic lineage with members of the genus Rhizobacter. Strain
      PLGR-1(T) was most closely related to Rhizobacter dauci DSM 11587(T) and
      Rhizobacter fulvus DSM 19916(T), with 16S rRNA gene sequence similarities of 98.5
      and 98.0 %, respectively. The DNA-DNA relatedness values between strain PLGR-1(T)
      and the type strains of Rhizobacter dauci and Rhizobacter fulvus were 46.3 and
      14.7 %, respectively. Based on the phenotypic, phylogenetic and genotypic data,
      strain PLGR-1(T) is considered to represent a novel species of the genus
      Rhizobacter, for which the name Rhizobacter bergeniae sp. nov. is proposed. The
      type strain is PLGR-1(T) ( = CCTCC AB 2013018(T) = KCTC 32299(T) = LMG 27607(T)).

PMID- 25389150
TI  - Lutibacter oricola sp. nov., a marine bacterium isolated from seawater.
AB  - A bacterial strain, UDC377(T), was isolated from seawater samples collected at
      Seo-do on the coast of Dokdo island in the East Sea, and was subjected to
      taxonomic study using a polyphasic approach. Strain UDC377(T) was pale-yellow,
      Gram-staining-negative, non-motile, rod-shaped and aerobic. The strain grew
      optimally at 25-28  degrees C, in the presence of 2 % (w/v) NaCl and at pH 7.0
      7.5. Strain UDC377(T) produced carotenoid pigments; however, it did not produce
      flexirubin-type pigments. Phylogenetic analysis based on 16S rRNA gene sequences
      showed that strain UDC377(T) clustered with members of the genus Lutibacter and
      appeared most closely related to Lutibacter agarilyticus KYW566(T) (96.0 % 16S
      rRNA gene sequence similarity) followed by L. aestuarii MA-My1(T) (95.0 %), L.
      litoralis CL-TF09(T) (94.9 %), L. maritimus S7-2(T) (94.1 %) and L. flavus
      IMCC1507(T) (94.0 %). The DNA G+C content of strain UDC377(T) was 30.8 mol%.
      Strain UDC377(T) contained MK-6 as the predominant menaquinone, iso-C15 : 0 3-OH,
      iso-C15 : 0 and iso-C16 : 0 3-OH as the major fatty acids, and
      phosphatidylethanolamine, two unknown aminolipids and six unknown lipids as the
      major polar lipids. Based on phenotypic properties and phylogenetic data
      presented, strain UDC377(T) is considered to represent a novel species of the
      genus Lutibacter, for which the name Lutibacter oricola sp. nov. is proposed. The
      type strain is UDC377(T) ( = DSM 24956(T) = KCTC 23668(T)).

PMID- 25389151
TI  - Mycobacterium celeriflavum sp. nov., a rapidly growing scotochromogenic bacterium
      isolated from clinical specimens.
AB  - Six strains of a rapidly growing scotochromogenic mycobacterium were isolated
      from pulmonary specimens of independent patients. Biochemical and cultural tests
      were not suitable for their identification. The mycolic acid pattern analysed by
      HPLC was different from that of any other mycobacterium. Genotypic
      characterization, targeting seven housekeeping genes, revealed the presence of
      microheterogeneity in all of them. Different species were more closely related to
      the test strains in various regions: the type strain of Mycobacterium moriokaense
      showed 99.0 % 16S rRNA gene sequence similarity, and 91.5-96.5 % similarity for
      the remaining six regions. The whole genome sequences of the proposed type strain
      and that of M. moriokaense presented an average nucleotide identity (ANI) of 82.9
      %. Phylogenetic analysis produced poorly robust trees in most genes with the
      exception of rpoB and sodA where Mycobacterium flavescens and Mycobacterium
      novocastrense were the closest species. This phylogenetic relatedness was
      confirmed by the tree inferred from five concatenated genes, which was very
      robust. The polyphasic characterization of the test strains, supported by the ANI
      value, demonstrates that they belong to a previously unreported species, for
      which the name Mycobacterium celeriflavum sp. nov. is proposed. The type strain
      is AFPC-000207(T) ( = DSM 46765(T) = JCM 18439(T)).

PMID- 25389152
TI  - Nesterenkonia alkaliphila sp. nov., an alkaliphilic, halotolerant actinobacteria
      isolated from the western Pacific Ocean.
AB  - A Gram-staining-positive, aerobic, motile and non-spore-forming actinobacteria,
      designated strain F10(T), was isolated from a deep-sea sediment of the western
      Pacific Ocean. Phylogenetic and phenotypic properties of the organism supported
      that it belonged to the genus Nesterenkonia. Strain F10(T) shared highest 16S
      rRNA gene sequence similarity of 96.8 % with Nesterenkonia aethiopica DSM
      17733(T), followed by Nesterenkonia xinjiangensis YIM 70097(T) (96.7 %) and
      Nesterenkonia alba CAAS 252(T) (96.6 %). The organism grew at 4-50  degrees C, at
      pH 7.0-12.0 and in the presence of 0-12 % (w/v) NaCl, with optimal growth
      occurring at 40  degrees C, at pH 9.0 and in the presence of 1 % (w/v) NaCl. The
      peptidoglycan type was A4(alpha), l-Lys-Gly-l-Glu. The polar lipid profile of
      strain F10(T) consisted of diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylinositol, two unknown glycolipids and two unknown lipids. The isolate
      contained MK-9 (92 %) and MK-8 (5.8 %) as the major components of the menaquinone
      system, and anteiso-C17 : 0 (50.9 %) and anteiso-C15 : 0 (29.8 %) as the
      predominant fatty acids. The G+C content of the genomic DNA of strain F10(T) was
      66.2 mol%. Based on phenotypic, genotypic and phylogenetic analyses, strain
      F10(T) represents a novel species of the genus Nesterenkonia for which the name
      Nesterenkonia alkaliphila sp. nov. is proposed. The type strain is F10(T) ( = LMG
      28112(T) = CGMCC 1.12781(T) = JCM 19766(T) = MCCC 1A09946(T)).

PMID- 25389153
TI  - Neisseria weaveri Andersen et al. 1993 is a later heterotypic synonym of
      Neisseria weaveri Holmes et al. 1993.
AB  - Two species of the genus Neisseria, namely Neisseria weaveri Andersen et al. 1993
      and Neisseria weaveri Holmes et al. 1993, were simultaneously proposed and
      described in the same volume of International Journal of Systematic Bacteriology,
      and have been maintained as heterotypic homonyms. However, the identical 16S rRNA
      gene sequence and high (99.1 %) average nucleotide identity (ANI) between the
      genome sequences of the two type strains implied that these two taxa should be
      united as a single genomic species. To clarify their taxonomic status, phenotypic
      properties including enzymic activities and substrate-utilization profiles were
      investigated. The results demonstrated that the two taxa have no pronounced
      differences and should constitute a single species. Therefore, the
      reclassification of N. weaveri Andersen et al. 1993 as a later heterotypic
      synonym of N. weaveri Holmes et al. 1993 is proposed.

PMID- 25389154
TI  - Quality in primary care.

PMID- 25389155
TI  - A case of cerebral venous sinus thrombosis associated with Crohn's disease:
      dilemma in management.
AB  - Inflammatory bowel disease (IBD) is known to increase the risk of venous
      thromboembolism. Cerebral venous sinus thrombosis (CVST) is a rare but important
      complication of IBD. Timely diagnosis, particularly in younger patients, requires
      a high level of suspicion in order to prevent potentially devastating
      complications such as hemorrhage or venous infarction. The paper presents a 44
      year-old Caucasian woman with a previous history of Crohn's disease and deep
      venous thrombosis. Magnetic resonance imaging confirmed the diagnosis of CVST.
      Achieving therapeutic anticoagulation with warfarin was difficult, due to
      presumed pharmacological interaction between warfarin and 6-mercaptopurine.
      Clinicians should have a high index of suspicion for CVST when a patient with
      Crohn's disease presents with acute headache, and be aware of challenges related
      to medical management. 

PMID- 25389156
TI  - Compact high-performance continuous-wave double-resonance rubidium standard with
      1.4 * 10(-13) tau(-1/2) stability.
AB  - We present our studies on a compact high-performance continuous wave (CW) double
      resonance (DR) rubidium frequency standard in view of future portable
      applications. Our clock exhibits a short-term stability of 1.4 * 10(-13) tau(
      1/2), consistent with the short-term noise budget for an optimized DR signal. The
      metrological studies on the medium- to longterm stability of our Rb standard with
      measured stabilities are presented. The dependence of microwave power shift on
      light intensity, and the possibility to suppress the microwave power shift is
      demonstrated. The instabilities arising from the vapor cell geometric effect are
      evaluated, and are found to act on two different time scales (fast and slow stem
      effects). The resulting medium- to long-term stability limit is around 5.5 * 10(
      14). Further required improvements, particularly focusing on medium- to long-term
      clock performance, are discussed. 

PMID- 25389157
TI  - Effect of subaperture beamforming on phase coherence imaging.
AB  - High-frame-rate echocardiography using unfocused transmit beams and parallel
      receive beamforming is a promising method for evaluation of cardiac function,
      such as imaging of rapid propagation of vibration of the heart wall resulting
      from electrical stimulation of the myocardium. In this technique, high temporal
      resolution is realized at the expense of spatial resolution and contrast. The
      phase coherence factor has been developed to improve spatial resolution and
      contrast in ultrasonography. It evaluates the variance in phases of echo signals
      received by individual transducer elements after delay compensation, as in the
      conventional delay-andsum beamforming process. However, the phase coherence
      factor suppresses speckle echoes because phases of speckle echoes fluctuate as a
      result of interference of echoes. In the present study, the receiving aperture
      was divided into several subapertures, and conventional delay-and-sum beamforming
      was performed with respect to each subaperture to suppress echoes from scatterers
      except for that at a focal point. After subaperture beamforming, the phase
      coherence factor was obtained from beamformed RF signals from respective
      subapertures. By means of this procedure, undesirable echoes, which can interfere
      with the echo from a focal point, can be suppressed by subaperture beamforming,
      and the suppression of the phase coherence factor resulting from phase
      fluctuation caused by such interference can be avoided. In the present study, the
      effect of subaperture beamforming in high-frame-rate echocardiography with the
      phase coherence factor was evaluated using a phantom. By applying subaperture
      beamforming, the average intensity of speckle echoes from a diffuse scattering
      medium was significantly higher (-39.9 dB) than that obtained without subaperture
      beamforming (-48.7 dB). As for spatial resolution, the width at half-maximum of
      the lateral echo amplitude profile obtained without the phase coherence factor
      was 1.06 mm. By using the phase coherence factor, spatial resolution was improved
      significantly, and subaperture beamforming achieved a better spatial resolution
      of 0.75 mm than that of 0.78 mm obtained without subaperture beamforming. 

PMID- 25389158
TI  - Asynchronous compressed beamformer for portable diagnostic ultrasound systems.
AB  - State-of-the-art portable ultrasound imaging systems employ a small transducer
      array and a low carrier frequency to fit stringent constraints on power and form
      factor, and this tends to compromise the ultrasound imaging quality. In this
      paper, we present a low-complexity low-power asynchronous compressed beamformer
      (ACB) for portable diagnostic ultrasound. The proposed ACB integrates
      asynchronous sampling and compressive sensing (CS), and is capable of reducing
      data conversion power and handling a large data volume at the mixed-signal
      interface. A high-rate continuoustime ternary encoding (CT-TE) scheme eliminates
      the need for interpolation filters and coordinate rotation digital computer
      (CORDIC) units typically used in a conventional architecture. A split-projection
      least squares (SPLS) signal reconstruction algorithm is applied that replaces
      high-cost nonlinear signal recovery with a series of low-complexity and
      independent linear problems. Experiments with measured ultrasound data
      demonstrate the proposed ACB architecture, and the SPLS reconstruction algorithm
      achieves 9-fold data compression compared with Nyquist sampling. 

PMID- 25389159
TI  - Superharmonic imaging with chirp coded excitation: filtering spectrally
      overlapped harmonics.
AB  - Superharmonic imaging improves the spatial resolution by using the higher order
      harmonics generated in tissue. The superharmonic component is formed by combining
      the third, fourth, and fifth harmonics, which have low energy content and
      therefore poor SNR. This study uses coded excitation to increase the excitation
      energy. The SNR improvement is achieved on the receiver side by performing pulse
      compression with harmonic matched filters. The use of coded signals also
      introduces new filtering capabilities that are not possible with pulsed
      excitation. This is especially important when using wideband signals. For
      narrowband signals, the spectral boundaries of the harmonics are clearly
      separated and thus easy to filter; however, the available imaging bandwidth is
      underused. Wideband excitation is preferable for harmonic imaging applications to
      preserve axial resolution, but it generates spectrally overlapping harmonics that
      are not possible to filter in time and frequency domains. After pulse
      compression, this overlap increases the range side lobes, which appear as imaging
      artifacts and reduce the Bmode image quality. In this study, the isolation of
      higher order harmonics was achieved in another domain by using the fan chirp
      transform (FChT). To show the effect of excitation bandwidth in superharmonic
      imaging, measurements were performed by using linear frequency modulated chirp
      excitation with varying bandwidths of 10% to 50%. Superharmonic imaging was
      performed on a wire phantom using a wideband chirp excitation. Results were
      presented with and without applying the FChT filtering technique by comparing the
      spatial resolution and side lobe levels. Wideband excitation signals achieved a
      better resolution as expected, however range side lobes as high as -23 dB were
      observed for the superharmonic component of chirp excitation with 50% fractional
      bandwidth. The proposed filtering technique achieved >50 dB range side lobe
      suppression and improved the image quality without affecting the axial
      resolution. 

PMID- 25389160
TI  - Transverse spectral velocity estimation.
AB  - A transverse oscillation (TO)-based method for calculating the velocity spectrum
      for fully transverse flow is described. Current methods yield the mean velocity
      at one position, whereas the new method reveals the transverse velocity spectrum
      as a function of time at one spatial location. A convex array probe is used along
      with two different estimators based on the correlation of the received signal.
      They can estimate the velocity spectrum as a function of time as for ordinary
      spectrograms, but they also work at a beam-to-flow angle of 90 degrees . The
      approach is validated using simulations of pulsatile flow using the Womersly
      Evans flow model. The relative bias of the mean estimated frequency is 13.6% and
      the mean relative standard deviation is 14.3% at 90 degrees , where a traditional
      estimator yields zero velocity. Measurements have been conducted with an
      experimental scanner and a convex array transducer. A pump generated artificial
      femoral and carotid artery flow in the phantom. The estimated spectra degrade
      when the angle is different from 90 degrees , but are usable down to 60 degrees 
      to 70 degrees . Below this angle the traditional spectrum is best and should be
      used. The conventional approach can automatically be corrected for angles from 0
      degrees  to 70 degrees  to give fully quantitative velocity spectra without
      operator intervention. 

PMID- 25389161
TI  - Experimental evaluation of spectral-based quantitative ultrasound imaging using
      plane wave compounding.
AB  - Quantitative ultrasound (QUS) based on backscatter coefficient (BSC) estimation
      has shown potential for tissue characterization. Beamforming using plane wave
      compounding has advantages for echographic, Doppler, and elastographic imaging;
      however, to date, plane wave compounding has not been experimentally evaluated
      for the purpose of BSC estimation. In this study, two BSC-derived parameters
      (i.e., the BSC midband fit and intercept) were estimated from experimental data
      obtained using compound plane wave beamforming. For comparison, QUS parameters
      were also estimated from data obtained using both fixed focus and dynamic receive
      beamforming. An ultrasound imaging system equipped with a 9-MHz center frequency,
      64-element array was used to collect data up to a depth of 45 mm. Two gelatin
      phantoms with randomly distributed 20-MUm inclusions with a homogeneous scatterer
      concentration and a two-region scatterer concentration were used for assessing
      the precision and lateral resolution of QUS imaging, respectively. The use of
      plane wave compounding resulted in accurate QUS estimation (i.e., bias in the BSC
      parameters of less than 2 dB) and relatively constant lateral resolution (i.e.,
      BSC midband fit 10% to 90% rise distance ranging between 1.0 and 1.5 mm)
      throughout a 45 mm field of view. Although both fixed focus and dynamic receive
      beamforming provided the same performance around the focal depth, the reduction
      in SNR away from the focus resulted in a reduced field of view in the homogeneous
      phantom (i.e., only 28 mm). The lateral resolution also degraded away from the
      focus, with up to a 2-fold and 10-fold increase in the rise distance at 20 mm
      beyond the focal depth for dynamic receive and fixed focus beamforming,
      respectively. These results suggest that plane wave compounding has the potential
      to improve the performance of spectral-based quantitative ultrasound over other
      conventional beamforming strategies. 

PMID- 25389162
TI  - Uncertainties in ultrasonic particle sizing in solid-in-liquid suspensions.
AB  - Measurements of the frequency dependence of ultrasonic attenuation can be used as
      the basis for the estimation of particle size distributions (PSDs) in solid-in
      liquid suspensions. The method requires matching the attenuation simulated by a
      candidate PSD in combination with a wave propagation model to the measured
      function in a fitting procedure. Uncertainty in the type of candidate PSD,
      whether based on fractional volume or fractional number of the dispersed
      particles, can cause errors in the overall estimation process, particularly for
      the median particle size. These uncertainties are investigated in the first part
      of this paper. The second part deals with uncertainties associated with the
      values for the physical properties of the suspended particles, seven of which are
      required in the simulation stage. It is shown that the particle sizing exercise
      is relatively insensitive to all of the physical properties except density, for
      which values are necessary to an accuracy commensurable with that required for
      the two principal parameters associated with the PSD-median size and standard
      deviation. The discussion is limited to small (less than 1-MUm) silica particles
      dispersed in water. The results will have more general application. 

PMID- 25389163
TI  - Zernike ultrasonic tomography for fluid velocity imaging based on pipeline
      intrusive time-of-flight measurements.
AB  - In this paper, we propose a novel ultrasonic tomography method for pipeline flow
      field imaging, based on the Zernike polynomial series. Having intrusive multipath
      time-offlight ultrasonic measurements (difference in flight time and speed of
      ultrasound) at the input, we provide at the output tomograms of the fluid
      velocity components (axial, radial, and orthoradial velocity). Principally, by
      representing these velocities as Zernike polynomial series, we reduce the
      tomography problem to an ill-posed problem of finding the coefficients of the
      series, relying on the acquired ultrasonic measurements. Thereupon, this problem
      is treated by applying and comparing Tikhonov regularization and quadratically
      constrained l1 minimization. To enhance the comparative analysis, we additionally
      introduce sparsity, by employing SVD-based filtering in selecting Zernike
      polynomials which are to be included in the series. The first approach-Tikhonov
      regularization without filtering, is used because it is the most suitable method.
      The performances are quantitatively tested by considering a residual norm and by
      estimating the flow using the axial velocity tomogram. Finally, the obtained
      results show the relative residual norm and the error in flow estimation,
      respectively, ~0.3% and ~1.6% for the less turbulent flow and ~0.5% and ~1.8% for
      the turbulent flow. Additionally, a qualitative validation is performed by
      proximate matching of the derived tomograms with a flow physical model. 

PMID- 25389164
TI  - Introducing S-parameters for ultrasound-based structural health monitoring.
AB  - Scattering parameters (S-parameters) are the most common tools for characterizing
      microwave devices and high-frequency systems but have not been used for
      ultrasoundbased structural health monitoring (SHM) so far. In this paper, we
      present the theory, signal processing algorithms, and experimental results to
      demonstrate the applications of S-parameters for three common ultrasound-based
      SHM techniques, i.e., ultrasound pitch-catch, pulse-echo, and
      impedance/admittance measurements. The concept of the S-parameters is first
      introduced, followed by the discussions of extracting the time-domain ultrasound
      signals from the frequency-domain Sparameter measurements. The time-domain
      signals calculated from the measured S-parameters were compared with the
      oscilloscope measurements. Excellent agreements between these two sets of
      measurements were achieved. In addition, time-frequency analysis of the
      ultrasound inspection system based on the S-parameter measurements has also been
      performed. This work demonstrated that the S-parameters can serve as a versatile
      tool for ultrasound-based SHM. 

PMID- 25389165
TI  - 3-D reconstruction of sub-wavelength scatterers from the measurement of scattered
      fields in elastic waveguides.
AB  - In nondestructive testing, being able to remotely locate and size defects with
      good accuracy is an important requirement in many industrial sectors, such as the
      petrochemical, nuclear, and aerospace industries. The potential of ultrasonic
      guided waves is well known for this type of problem, but interpreting the
      measured data and extracting useful information about the defects remains
      challenging. This paper introduces a Bayesian approach to measuring the geometry
      of a defect while providing at the same time an estimate of the uncertainty in
      the solution. To this end, a Markov-chain Monte Carlo algorithm is used to fit
      simulated scattered fields to the measured ones. Simulations are made with
      efficient models where the geometries of the defects are provided as input
      parameters, so that statistical information on the defect properties such as
      depth, shape, and dimensions can be obtained. The method is first investigated on
      simulations to evaluate its sensitivity to noise and to the amount of measured
      data, and it is then demonstrated on experimental data. The defect geometries
      vary from simple elliptical flat-bottomed holes to complex corrosion profiles. 

PMID- 25389166
TI  - Generalized theory of resonance scattering (GTRS) using the translational
      addition theorem for spherical wave functions.
AB  - The generalized theory of resonance scattering (GTRS) by an elastic spherical
      target in acoustics is extended to describe the arbitrary scattering of a finite
      beam using the addition theorem for the spherical wave functions of the first
      kind under a translation of the coordinate origin. The advantage of the proposed
      method over the standard discrete spherical harmonics transform previously used
      in the GTRS formalism is the computation of the off-axial beam-shape coefficients
      (BSCs) stemming from a closed-form partial-wave series expansion representing the
      axial BSCs in spherical coordinates. With this general method, the arbitrary
      acoustical scattering can be evaluated for any particle shape and size, whether
      the particle is partially or completely illuminated by the incident beam.
      Numerical examples for the axial and off-axial resonance scattering from an
      elastic sphere placed arbitrarily in the field of a finite circular piston
      transducer with uniform vibration are provided. Moreover, the 3-D resonance
      directivity patterns illustrate the theory and reveal some properties of the
      scattering. Numerous applications involving the scattering phenomenon in imaging,
      particle manipulation, and the characterization of multiphase flows can benefit
      from the present analysis because all physically realizable beams radiate
      acoustical waves from finite transducers as opposed to waves of infinite extent. 

PMID- 25389167
TI  - Circuit optomechanics: concepts and materials.
AB  - Nanophotonic integrated circuits offer unique advantages for studying the
      interaction of light fields with mechanical structures. Because nanoscale
      waveguides are closely size-matched to nanomechanical devices, strong
      optomechanical interactions arise which can be harnessed in optical systems. The
      additional mechanical degrees of freedom provided by optomechanical devices are
      of particular interest for material systems in which tunability of the optical
      properties is not readily available. Here, suitable materials for the realization
      of chip-based optomechanical circuits are discussed and analyzed in terms of
      performance and the achievable quality factors. In particular, materials that
      offer large electronic band gaps are of interest, because in this case broadband
      optical transparency is achieved, combined with reduced free carrier effects.
      Several device geometries that can be used for enhancing optical forces are
      presented which address both an increase in the field gradient and the net
      optical force through resonant enhancement. Combining a variety of optomechanical
      components into full circuits thus provides a new route toward functional
      nanophotonic circuits with applications in sensing and optical signal processing
      in a chip-scale framework. 

PMID- 25389168
TI  - Designing transmitting CMUT cells for airborne applications.
AB  - We report a new mode of airborne operation for capacitive micromachined
      ultrasonic transducers (CMUT), in which the plate motion spans the entire gap
      without collapsing and the transducer is driven by a sinusoidal voltage without a
      dc bias. We present equivalent-circuit-based design fundamentals for an airborne
      CMUT cell and verify the design targets using fabricated CMUTs. The performance
      limits for silicon plates are derived. We experimentally obtain 78.9 dB//20
      MUPa@1 m source level at 73.7 kHz, with a CMUT cell of radius 2.05 mm driven by
      71 V sinusoidal drive voltage at half the frequency. The measured quality factor
      is 120. We also study and discuss the interaction of the nonlinear transduction
      force and the nonlinearity of the plate compliance. 

PMID- 25389169
TI  - Mass-spring matching layers for high-frequency ultrasound transducers: a new
      technique using vacuum deposition.
AB  - We have developed a technique of applying multiple matching layers to high
      frequency (>30 MHz) imaging transducers, by using carefully controlled vacuum
      deposition alone. This technique uses a thin mass-spring matching layer approach
      that was previously described in a low-frequency (1 to 10 MHz) transducer design
      with epoxied layers. This mass- spring approach is more suitable to vacuum
      deposition in highfrequency transducers over the conventional quarter-wavelength
      resonant cavity approach, because thinner layers and more versatile material
      selection can be used, the difficulty in precisely lapping quarter-wavelength
      matching layers is avoided, the layers are less attenuating, and the layers can
      be applied to a curved surface. Two different 3-mm-diameter 45-MHz planar lithium
      niobate transducers and one geometrically curved 3-mm lithium niobate transducer
      were designed and fabricated using this matching layer approach with copper as
      the mass layer and parylene as the spring layer. The first planar lithium niobate
      transducer used a single mass-spring matching network, and the second planar
      lithium niobate transducer used a single mass-spring network to approximate the
      first layer in a dual quarter-wavelength matching layer system in addition to a
      conventional quarter-wavelength layer as the second matching layer. The curved
      lithium niobate transducer was press focused and used a similar mass-spring plus
      quarter-wavelength matching layer network. These transducers were then compared
      with identical transducers with no matching layers and the performance
      improvement was quantified. The bandwidth of the lithium niobate transducer with
      the single mass-spring layer was measured to be 46% and the insertion loss was
      measured to be -21.9 dB. The bandwidth and insertion loss of the lithium niobate
      transducer with the mass-spring network plus quarter-wavelength matching were
      measured to be 59% and -18.2 dB, respectively. These values were compared with
      the unmatched transducer, which had a bandwidth of 28% and insertion loss of 
      34.1 dB. The bandwidth and insertion loss of the curved lithium niobate
      transducer with the mass-spring plus quarter-wavelength matching layer
      combination were measured to be 68% and -26 dB, respectively; this compared with
      the measured unmatched bandwidth and insertion loss of 35% and -37 dB. All
      experimentally measured values were in excellent agreement with theoretical
      Krimholtz-Leedom-Matthaei (KLM) model predictions. 

PMID- 25389172
TI  - Multi-disciplinary team meetings in stroke rehabilitation: an observation study
      and conceptual framework.
AB  - OBJECTIVE: To explore how multi-disciplinary team meetings operate in stroke
      rehabilitation. DESIGN: Non-participant observation of multi-disciplinary team
      meetings and semi-structured interviews with attending staff. SETTING AND
      PARTICIPANTS: Twelve meetings were observed (at least one at each site) and 18
      staff (one psychologist, one social worker; four nurses; four physiotherapists
      four occupational therapists, two speech and language therapists, one stroke co
      ordinator and one stroke ward manager) were interviewed in eight in-patient
      stroke rehabilitation units. RESULTS: Multi-disciplinary team meetings in stroke
      rehabilitation were complex, demanding and highly varied. A model emerged which
      identified the main inputs to influence conduct of the meetings were personal
      contributions of the members and structure and format of the meetings. These were
      mediated by the team climate and leadership skills of the chair. The desired
      outputs; clinical decisions and the attributes of apparently effective meetings
      were identified by the staff. A notable difference between the meetings that
      staff considered effective and those that were not, was their structure and
      format. Successful meetings tended to feature a set agenda, structured
      documentation; formal use of measurement tools; pre-meeting preparation and
      skilled chairing. These features were often absent in meetings perceived to be
      ineffective. CONCLUSIONS: The main features of operation of multi-disciplinary
      team meetings have been identified which will enable assessment tools and
      interventions to improve effectiveness to be developed.

PMID- 25389173
TI  - Genomic characterization of variable surface antigens reveals a telomere position
      effect as a prerequisite for RNA interference-mediated silencing in Paramecium
      tetraurelia.
AB  - Antigenic or phenotypic variation is a widespread phenomenon of expression of
      variable surface protein coats on eukaryotic microbes. To clarify the mechanism
      behind mutually exclusive gene expression, we characterized the genetic
      properties of the surface antigen multigene family in the ciliate Paramecium
      tetraurelia and the epigenetic factors controlling expression and silencing.
      Genome analysis indicated that the multigene family consists of intrachromosomal
      and subtelomeric genes; both classes apparently derive from different gene
      duplication events: whole-genome and intrachromosomal duplication. Expression
      analysis provides evidence for telomere position effects, because only
      subtelomeric genes follow mutually exclusive transcription. Microarray analysis
      of cultures deficient in Rdr3, an RNA-dependent RNA polymerase, in comparison to
      serotype-pure wild-type cultures, shows cotranscription of a subset of
      subtelomeric genes, indicating that the telomere position effect is due to a
      selective occurrence of Rdr3-mediated silencing in subtelomeric regions. We
      present a model of surface antigen evolution by intrachromosomal gene duplication
      involving the maintenance of positive selection of structurally relevant regions.
      Further analysis of chromosome heterogeneity shows that alternative telomere
      addition regions clearly affect transcription of closely related genes.
      Consequently, chromosome fragmentation appears to be of crucial importance for
      surface antigen expression and evolution. Our data suggest that RNAi-mediated
      control of this genetic network by trans-acting RNAs allows rapid epigenetic
      adaptation by phenotypic variation in combination with long-term genetic
      adaptation by Darwinian evolution of antigen genes. IMPORTANCE: Alternating
      surface protein structures have been described for almost all eukaryotic
      microbes, and a broad variety of functions have been described, such as virulence
      factors, adhesion molecules, and molecular camouflage. Mechanisms controlling
      gene expression of variable surface proteins therefore represent a powerful tool
      for rapid phenotypic variation across kingdoms in pathogenic as well as free
      living eukaryotic microbes. However, the epigenetic mechanisms controlling
      synchronous expression and silencing of individual genes are hardly understood.
      Using the ciliate Paramecium tetraurelia as a (epi)genetic model, we showed that
      a subtelomeric gene position effect is associated with the selective occurrence
      of RNAi-mediated silencing of silent surface protein genes, suggesting small
      interfering RNA (siRNA)-mediated epigenetic cross talks between silent and active
      surface antigen genes. Our integrated genomic and molecular approach discloses
      the correlation between gene position effects and siRNA-mediated trans-silencing,
      thus providing two new parameters for regulation of mutually exclusive gene
      expression and the genomic organization of variant gene families.

PMID- 25389174
TI  - Characterization of a replication-incompetent pseudorabies virus mutant lacking
      the sole immediate early gene IE180.
AB  - The alphaherpesvirus pseudorabies virus (PRV) encodes a single immediate early
      gene called IE180. The IE180 protein is a potent transcriptional activator of
      viral genes involved in DNA replication and RNA transcription. A PRV mutant with
      both copies of IE180 deleted was constructed 20 years ago (S. Yamada and M.
      Shimizu, Virology 199:366-375, 1994, doi:10.1006/viro.1994.1134), but propagation
      of the mutant depended on complementing cell lines that expressed the toxic IE180
      protein constitutively. Recently, Oyibo et al. constructed a novel set of PRV
      IE180 mutants and a stable cell line with inducible IE180 expression (H. Oyibo,
      P. Znamenskiy, H. V. Oviedo, L. W. Enquist, A. Zador, Front. Neuroanat. 8:86,
      2014, doi:10.3389/fnana.2014.00086), which we characterized further here. These
      mutants failed to replicate new viral genomes, synthesize immediate early, early,
      or late viral proteins, and assemble infectious virions. The PRV IE180-null
      mutant did not form plaques in epithelial cell monolayers and could not spread
      from primary infected neurons to second-order neurons in culture. PRV IE180-null
      mutants lacked the property of superinfection exclusion. When PRV IE180-null
      mutants infected cells first, subsequent superinfecting viruses were not blocked
      in cell entry and formed replication compartments in epithelial cells,
      fibroblasts, and neurons. Cells infected with PRV IE180-null mutants survived as
      long as uninfected cells in culture while expressing a fluorescent reporter gene.
      Transcomplementation with IE180 in epithelial cells restored all mutant
      phenotypes to wild type. The conditional expression of PRV IE180 protein enables
      the propagation of replication-incompetent PRV IE180-null mutants and will
      facilitate construction of long-term single-cell-infecting PRV mutants for
      precise neural circuit tracing and high-capacity gene delivery vectors.
      IMPORTANCE: Pseudorabies virus (PRV) is widely used for neural tracing in animal
      models. The virus replicates and spreads between synaptically connected neurons.
      Current tracing strains of PRV are cytotoxic and kill infected cells. Infected
      cells exclude superinfection with a second virus, limiting multiple virus
      infections in circuit tracing. By removing the only immediate early gene of PRV
      (called IE180), the mutant virus will not replicate or spread in epithelial
      cells, fibroblasts, or neurons. The wild-type phenotype can be restored by
      transcomplementation of infected cells with IE180. The PRV IE180-null mutant can
      express fluorescent reporters for weeks in cells with no toxicity; infected cells
      survive as long as uninfected cells. Infection with the mutant virus allows
      superinfection of the same cell with a second virus that can enter and replicate.
      The PRV IE180-null mutant will permit conditional long-term tracing in animals
      and is a high-capacity vector for gene delivery.

PMID- 25389175
TI  - Mucins suppress virulence traits of Candida albicans.
AB  - Candida albicans is the most prevalent fungal pathogen of humans, causing a
      variety of diseases ranging from superficial mucosal infections to deep-seated
      systemic invasions. Mucus, the gel that coats all wet epithelial surfaces,
      accommodates C. albicans as part of the normal microbiota, where C. albicans
      resides asymptomatically in healthy humans. Through a series of in vitro
      experiments combined with gene expression analysis, we show that mucin
      biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped
      morphology in C. albicans in which a range of genes related to adhesion,
      filamentation, and biofilm formation are downregulated. We also show that
      corresponding traits are suppressed, rendering C. albicans impaired in forming
      biofilms on a range of different synthetic surfaces and human epithelial cells.
      Our data suggest that mucins can manipulate C. albicans physiology, and we
      hypothesize that they are key environmental signals for retaining C. albicans in
      the host-compatible, commensal state. IMPORTANCE: The yeast Candida albicans
      causes both superficial infections of the mucosa and life-threatening infections
      upon entering the bloodstream. However, C. albicans is not always harmful and can
      exist as part of the normal microbiota without causing disease. Internal body
      surfaces that are susceptible to infection by C. albicans are coated with mucus,
      which we hypothesize plays an important role in preventing infections. Here, we
      show that the main components of mucus, mucin glycoproteins, suppress virulence
      attributes of C. albicans at the levels of gene expression and the corresponding
      morphological traits. Specifically, mucins suppress attachment to plastic
      surfaces and human cells, the transition to cell-penetrating hyphae, and the
      formation of biofilms (drug-resistant microbial communities). Additionally,
      exposure to mucins induces an elongated morphology that physically resembles the
      mating-competent opaque state but is phenotypically distinct. We suggest that
      mucins are potent antivirulence molecules that have therapeutic potential for
      suppressing C. albicans infections.

PMID- 25389176
TI  - Release of nonstop ribosomes is essential.
AB  - Bacterial ribosomes frequently translate to the 3' end of an mRNA without
      terminating at a stop codon. Almost all bacteria use the transfer-messenger RNA
      (tmRNA)-based trans-translation pathway to release these "nonstop" ribosomes and
      maintain protein synthesis capacity. trans-translation is essential in some
      species, but in others, such as Caulobacter crescentus, trans-translation can be
      inactivated. To determine why trans-translation is dispensable in C. crescentus,
      a Tn-seq screen was used to identify genes that specifically alter growth in
      cells lacking ssrA, the gene encoding tmRNA. One of these genes, CC1214, was
      essential in DeltassrA cells. Purified CC1214 protein could release nonstop
      ribosomes in vitro. CC1214 is a homolog of the Escherichia coli ArfB protein, and
      using the CC1214 sequence, ArfB homologs were identified in the majority of
      bacterial phyla. Most species in which ssrA has been deleted contain an ArfB
      homolog, suggesting that release of nonstop ribosomes may be essential in most or
      all bacteria. IMPORTANCE: Genes that are conserved across large phylogenetic
      distances are expected to confer a selective advantage. The genes required for
      trans-translation, ssrA and smpB, have been found in >99% of sequenced bacterial
      genomes, suggesting that they are broadly important. However, these genes can be
      deleted in some species without loss of viability. The identification and
      characterization of C. crescentus ArfB reveals why trans-translation is not
      essential in C. crescentus and suggests that many other bacteria are likely to
      use ArfB to survive when trans-translation is compromised.

PMID- 25389177
TI  - Metastable intermediates as stepping stones on the maturation pathways of viral
      capsids.
AB  - As they mature, many capsids undergo massive conformational changes that
      transform their stability, reactivity, and capacity for DNA. In some cases,
      maturation proceeds via one or more intermediate states. These structures
      represent local minima in a rich energy landscape that combines contributions
      from subunit folding, association of subunits into capsomers, and intercapsomer
      interactions. We have used scanning calorimetry and cryo-electron microscopy to
      explore the range of capsid conformations accessible to bacteriophage HK97. To
      separate conformational effects from those associated with covalent cross-linking
      (a stabilization mechanism of HK97), a cross-link-incompetent mutant was used.
      The mature capsid Head I undergoes an endothermic phase transition at 60 degrees
      C in which it shrinks by 7%, primarily through changes in its hexamer
      conformation. The transition is reversible, with a half-life of ~3 min; however,
      >50% of reverted capsids are severely distorted or ruptured. This observation
      implies that such damage is a potential hazard of large-scale structural changes
      such as those involved in maturation. Assuming that the risk is lower for smaller
      changes, this suggests a rationalization for the existence of metastable
      intermediates: that they serve as stepping stones that preserve capsid integrity
      as it switches between the radically different conformations of its precursor and
      mature states. IMPORTANCE: Large-scale conformational changes are widespread in
      virus maturation and infection processes. These changes are accompanied by the
      release of conformational free energy as the virion (or fusogenic glycoprotein)
      switches from a precursor state to its mature state. Each state corresponds to a
      local minimum in an energy landscape. The conformational changes in capsid
      maturation are so radical that the question arises of how maturing capsids avoid
      being torn apart. Offering proof of principle, severe damage is inflicted when a
      bacteriophage HK97 capsid reverts from the (nonphysiological) state that it
      enters when heated past 60  degrees C. We suggest that capsid proteins have been
      selected in part by the criterion of being able to avoid sustaining collateral
      damage as they mature. One way of achieving this---as with the HK97 capsid
      involves breaking the overall transition down into several smaller steps in which
      the risk of damage is reduced.

PMID- 25389178
TI  - QseC inhibitors as an antivirulence approach for Gram-negative pathogens.
AB  - Invasive pathogens interface with the host and its resident microbiota through
      interkingdom signaling. The bacterial receptor QseC, which is a membrane-bound
      histidine sensor kinase, responds to the host stress hormones epinephrine and
      norepinephrine and the bacterial signal AI-3, integrating interkingdom signaling
      at the biochemical level. Importantly, the QseC signaling cascade is exploited by
      many bacterial pathogens to promote virulence. Here, we translated this basic
      science information into development of a potent small molecule inhibitor of
      QseC, LED209. Extensive structure activity relationship (SAR) studies revealed
      that LED209 is a potent prodrug that is highly selective for QseC. Its warhead
      allosterically modifies lysines in QseC, impairing its function and preventing
      the activation of the virulence program of several Gram-negative pathogens both
      in vitro and during murine infection. LED209 does not interfere with pathogen
      growth, possibly leading to a milder evolutionary pressure toward drug
      resistance. LED209 has desirable pharmacokinetics and does not present toxicity
      in vitro and in rodents. This is a unique antivirulence approach, with a proven
      broad-spectrum activity against multiple Gram-negative pathogens that cause
      mammalian infections. IMPORTANCE: There is an imminent need for development of
      novel treatments for infectious diseases, given that one of the biggest
      challenges to medicine in the foreseeable future is the emergence of microbial
      antibiotic resistance. Here, we devised a broad-spectrum antivirulence approach
      targeting a conserved histidine kinase, QseC, in several Gram-negative pathogens
      that promotes their virulence expression. The LED209 QseC inhibitor has a unique
      mode of action by acting as a prodrug scaffold to deliver a warhead that
      allosterically modifies QseC, impeding virulence in several Gram-negative
      pathogens.

PMID- 25389179
TI  - Superresolution imaging captures carbohydrate utilization dynamics in human gut
      symbionts.
AB  - Gut microbes play a key role in human health and nutrition by catabolizing a wide
      variety of glycans via enzymatic activities that are not encoded in the human
      genome. The ability to recognize and process carbohydrates strongly influences
      the structure of the gut microbial community. While the effects of diet on the
      microbiota are well documented, little is known about the molecular processes
      driving metabolism. To provide mechanistic insight into carbohydrate catabolism
      in gut symbionts, we studied starch processing in real time in the model
      Bacteroides thetaiotaomicron starch utilization system (Sus) by single-molecule
      fluorescence. Although previous studies have explored Sus protein structure and
      function, the transient interactions, assembly, and collaboration of these outer
      membrane proteins have not yet been elucidated in live cells. Our live-cell
      superresolution imaging reveals that the polymeric starch substrate dynamically
      recruits Sus proteins, serving as an external scaffold for bacterial membrane
      assembly of the Sus complex, which may promote efficient capturing and
      degradation of starch. Furthermore, by simultaneously localizing multiple Sus
      outer membrane proteins on the B. thetaiotaomicron cell surface, we have
      characterized the dynamics and stoichiometry of starch-induced Sus complex
      assembly on the molecular scale. Finally, based on Sus protein knockout strains,
      we have discerned the mechanism of starch-induced Sus complex assembly in live
      anaerobic cells with nanometer-scale resolution. Our insights into the starch
      induced outer membrane protein assembly central to this conserved nutrient uptake
      mechanism pave the way for the development of dietary or pharmaceutical therapies
      to control Bacteroidetes in the intestinal tract to enhance human health and
      treat disease. IMPORTANCE: In this study, we used nanometer-scale superresolution
      imaging to reveal dynamic interactions between the proteins involved in starch
      processing by the prominent human gut symbiont Bacteroides thetaiotaomicron in
      real time in live cells. These results represent the first working model of
      starch utilization system (Sus) complex assembly and function during glycan
      catabolism and are likely to describe aspects of how other Sus-like systems
      function in human gut Bacteroidetes. Our results provide unique mechanistic
      insights into a glycan catabolism strategy that is prevalent within the human gut
      microbial community. Proper understanding of this conserved nutrient uptake
      mechanism is essential for the development of dietary or pharmaceutical therapies
      to control intestinal tract microbial populations, to enhance human health, and
      to treat disease.

PMID- 25389180
TI  - Noncanonical G-protein-dependent modulation of osteoclast differentiation and
      bone resorption mediated by Pasteurella multocida toxin.
AB  - Pasteurella multocida toxin (PMT) induces atrophic rhinitis in animals, which is
      characterized by a degradation of nasal turbinate bones, indicating an effect of
      the toxin on bone cells such as osteoblasts and osteoclasts. The underlying
      molecular mechanism of PMT was defined as a persistent activation of
      heterotrimeric G proteins by deamidation of a specific glutamine residue. Here,
      we show that PMT acts directly on osteoclast precursor cells such as bone marrow
      derived CD14(+) monocytes and RAW246.7 cells to induce osteoclastogenesis as
      measured by expression of osteoclast-specific markers such as tartrate-resistant
      acid phosphatase and bone resorption activity. Treatment performed solely with
      PMT stimulates osteoclast differentiation, showing a receptor activator of
      nuclear factor-kappaB ligand (RANKL)-independent action of the toxin. The
      underlying signal transduction pathway was defined as activation of the
      heterotrimeric G proteins Galphaq/11 leading to the transactivation of Ras and
      the mitogen-activated protein kinase pathway. Galphaq/11 transactivates Ras via
      its effector phospholipase Cbeta-protein kinase C (PKC) involving proline-rich
      tyrosine kinase 2 (Pyk2). PMT-induced activation of the mitogen-activated protein
      kinase pathway results in stimulation of the osteoclastogenic transcription
      factors AP-1, NF-kappaB, and NFATc1. In addition, Ca(2+)-dependent calcineurin
      activation of NFAT is crucial for PMT-induced osteoclastogenesis. The data not
      only elucidate a rationale for PMT-dependent bone loss during atrophic rhinitis
      but also highlight a noncanonical, G-protein-dependent pathway toward bone
      resorption that is distinct from the RANKL-RANK pathway but mimics it. We define
      heterotrimeric G proteins as as-yet-underestimated entities/players in the
      maturation of osteoclasts which might be of pharmacological relevance.
      IMPORTANCE: Pasteurella multocida toxin (PMT) induces degradation of nasal
      turbinate bones, leading to the syndrome of atrophic rhinitis. Recently, the
      molecular mechanism and substrate specificity of PMT were identified. The toxin
      activates heterotrimeric G proteins by a covalent modification. However, the
      mechanism by which PMT induces bone degradation is poorly understood. Our report
      demonstrates a direct effect of PMT on osteoclast precursor cells, leading to
      maturation of bone-degrading osteoclasts. Interestingly, PMT stimulates
      osteoclastogenesis independently of the cytokine RANKL, which is a key factor in
      induction of osteoclast differentiation. This implicates a noncanonical
      osteoclastogenic signaling pathway induced by PMT. The elucidated Galphaq/11
      dependent osteoclastogenic signal transduction pathway ends in osteoclastogenic
      NFAT signaling. The noncanonical, heterotrimeric G protein-dependent osteoclast
      differentiation process may be of pharmacological relevance, as members of this
      pathway are highly druggable. In particular, modulation of G protein-coupled
      receptor activity in osteoclast progenitors by small molecules might be of
      specific interest.

PMID- 25389182
TI  - Late presentation to hospital services necessitates greater community-based care
      for malnourished children.
AB  - The records for all paediatric deaths (ages 0-14) in a large hospital in urban
      Southern Africa were examined for a 3 year period (January 2007 to February
      2010), to explore the role of malnutrition in paediatric mortality in this
      region. A total of 516 records were obtained, demonstrating that malnutrition was
      the primary or secondary cause of death in 35% of cases. It was also found that
      children presented very late to hospital services, with an average length of
      final admission of only 0-3 days. The rate of human immunodeficiency virus (HIV)
      infection was found to be very high, although low testing rates limits the
      analysis of these figures. Malnutrition remains an important factor in paediatric
      mortality in southern Africa, contributing to approximately 35% of deaths.
      Furthermore, fatal cases presented very late to hospital services. In light of
      this, increased community-based therapy would be beneficial. Implementation of
      universal HIV testing would also be valuable. 

PMID- 25389181
TI  - Depression in caregivers of status-naive pediatric HIV patients participating in
      a status disclosure study in Haiti and the Dominican Republic: preliminary
      report.
AB  - A pilot study is underway to assess safety and acceptability of an intervention
      to disclose their HIV infection status to status-naive pediatric antiretroviral
      therapy patients in Hispaniola [the island shared by Haiti and the Dominican
      Republic (DR)]. Of 22 Haiti and 47 DR caregivers recruited to date, 68.2% Haiti
      and 34.0% DR caregivers had clinically significant depressive symptomatology at
      the time of enrollment (p = 0.008). Depressive symptom prevalence was higher in
      Haiti caregivers who were female (81.3% vs. 0 in males; p = 0.02) and in DR
      caregivers who were patients' mothers (50.0%) or grandmothers (66.7%; 56.0%
      combined) than others (9.1%), (p < 0.001). Internalized stigma was more commonly
      reported by Haiti (85.7%) than DR (53.2%; p = 0.01) caregivers; 56.4% of Haiti
      and DR caregivers reporting internalized stigma vs. 26.1% of caregivers denying
      it had depressive symptoms (p = 0.02). Depression is common in Hispaniola
      caregivers possibly affecting disclosure timing. Study participation presents
      opportunities for addressing caregiver depression. 

PMID- 25389183
TI  - Barriers to use of oral rehydration salts for child diarrhea in the private
      sector: evidence from India.
AB  - Diarrhea is the second leading cause of child mortality in India. Most deaths are
      cheaply preventable with the use of oral rehydration salts (ORS), yet many health
      providers still fail to provide ORS to children seeking diarrheal care. In this
      study, we use survey data to assess whether children visiting private providers
      for diarrheal care were less likely to use ORS than those visiting public
      providers. Results suggest that children who visited private providers were 9.5
      percentage points less likely to have used ORS than those who visited public
      providers (95% CI 5-14). We complimented these results with in-depth interviews
      of 21 public and 17 private doctors in Gujarat, India, assessing potential
      drivers of public-private disparities in ORS use. Interview results suggested
      that lack of direct medication dispensing in the private sector might be a key
      barrier to ORS use in the private sector. 

PMID- 25389184
TI  - "Alarming" report shows NHS finances are diving into the red.

PMID- 25389186
TI  - Mapping of the interaction domains of the Crimean-Congo hemorrhagic fever virus
      nucleocapsid protein.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the genus Nairovirus
      of the family Bunyaviridae, that can cause severe haemorrhagic fever in humans,
      with mortality rates above 30  %. CCHFV is the most widespread of the tick-borne
      human viruses and it is endemic in areas of central Asia, the Middle East, Africa
      and southern Europe. Its viral genome consists of three negative-sense RNA
      segments. The large segment (L) encodes a viral RNA-dependent RNA polymerase (L
      protein), the small segment (S) encodes the nucleocapsid protein (N protein) and
      the medium segment (M) encodes the envelope proteins. The N protein of
      bunyaviruses binds genomic RNA, forming the viral ribonucleoprotein (RNP)
      complex. The L protein interacts with these RNP structures, allowing the
      initiation of viral replication. The N protein also interacts with actin,
      although the regions and specific residues involved in these interactions have
      not yet been described. Here, by means of immunoprecipitation and
      immunofluorescence assays, we identified the regions within the CCHFV N protein
      implicated in homo-oligomerization and actin binding. We describe the interaction
      of the N protein with the CCHFV L protein, and identify the N- and C-terminal
      regions within the L protein that might be necessary for the formation of these N
      L protein complexes. These results may guide the development of potent inhibitors
      of these complexes that could potentially block CCHFV replication.

PMID- 25389187
TI  - Factors intrinsic and extrinsic to blood hamper the development of a routine
      blood test for human prion diseases.
AB  - Development of numerous advanced techniques in recent years have allowed
      detection of the pathological prion protein (PrP(TSE)), the unique marker of
      transmissible spongiform encephalopathies (TSEs, or prion diseases), in the blood
      of animals and humans; however, an ante mortem screening test that can be used
      for the routine diagnosis of human prion diseases remains unavailable. A
      critical, analytical review of all the diagnostic assays developed to date will
      allow an evaluation of progress in this field and may facilitate the
      identification of the possible reasons for this delay. Thus, in this review, I
      provide a detailed overview of the techniques currently available for detecting
      PrP(TSE) and other markers of the disease in blood, as well as an analysis of the
      significance, feasibility, reliability and application spectrum for these
      methods. I highlight that factors intrinsic and extrinsic to blood may interfere
      with the detection of PrP(TSE)/prions, and that this is not yet taken into
      account in current tests. This may inspire researchers in this field to not only
      aspire to increase test sensitivity, but also to adopt other strategies in order
      to identify and overcome the limitations that hamper the development of a
      successful routine blood test for prion diseases. 

PMID- 25389185
TI  - Glycoproteomic analysis of seven major allergenic proteins reveals novel post
      translational modifications.
AB  - Allergenic proteins such as grass pollen and house dust mite (HDM) proteins are
      known to trigger hypersensitivity reactions of the immune system, leading to what
      is commonly known as allergy. Key allergenic proteins including sequence variants
      have been identified but characterization of their post-translational
      modifications (PTMs) is still limited. Here, we present a detailed PTM(1)
      characterization of a series of the main and clinically relevant allergens used
      in allergy tests and vaccines. We employ Orbitrap-based mass spectrometry with
      complementary fragmentation techniques (HCD/ETD) for site-specific PTM
      characterization by bottom-up analysis. In addition, top-down mass spectrometry
      is utilized for targeted analysis of individual proteins, revealing hitherto
      unknown PTMs of HDM allergens. We demonstrate the presence of lysine-linked
      polyhexose glycans and asparagine-linked N-acetylhexosamine glycans on HDM
      allergens. Moreover, we identified more complex glycan structures than previously
      reported on the major grass pollen group 1 and 5 allergens, implicating important
      roles for carbohydrates in allergen recognition and response by the immune
      system. The new findings are important for understanding basic disease-causing
      mechanisms at the cellular level, which ultimately may pave the way for
      instigating novel approaches for targeted desensitization strategies and improved
      allergy vaccines. 

PMID- 25389188
TI  - Prevalence and Correlates of Self-Rated Posttraumatic Stress Disorder and
      Complicated Grief in a Community-Based Sample of Homicidally Bereaved
      Individuals.
AB  - People confronted with homicidal loss have to cope with separation distress,
      related to their loss, and traumatic distress, associated with the circumstances
      surrounding the death. These reactions are related to complicated grief (CG) and
      posttraumatic stress disorder (PTSD). The psychological effects for people who
      have lost someone through homicide, in terms of PTSD and CG, are largely unclear.
      This cross-sectional study (a) examined the prevalence of self-rated PTSD and
      self-rated CG in a community-based sample of 312 spouses, family members, and
      friends of homicide victims and (b) aimed to identify socio-demographic, loss
      related, and perpetrator-related correlates of PTSD and CG. Participants were
      recruited via support organizations for homicidally bereaved individuals in the
      Netherlands (i.e., support group), and by casemanagers of a governmental
      organization, which offers practical, non-psychological, support to bereaved
      families (i.e., casemanager group). Prevalence of self-rated PTSD was 30.9%
      (support group) and 37.5% (casemanager group), prevalence of CG was 82.7%
      (support group) and 80.6% (casemanager group). PTSD and CG severity scores varied
      as a function of the relationship with the victim; parents were at greater risk
      to develop emotional problems, compared with other relatives of the victim. Time
      since loss was negatively associated with PTSD and CG scores. 

PMID- 25389189
TI  - Attitudes About Human Trafficking: Individual Differences Related to Belief and
      Victim Blame.
AB  - Human trafficking is believed to oppress millions of people worldwide. Despite
      increased media attention and public awareness campaigns in recent years, no
      empirical research has examined public attitudes about human trafficking. The
      present study examined gender, sexual trauma history, and attitudes about human
      trafficking as they related to belief of a sex-trafficking scenario and
      willingness to blame the victim for the situation. Undergraduate students (N =
      409) at a large private university in the Northeastern United States completed
      measures in which they responded to a vignette portraying sex trafficking in the
      United States. Participants also reported their personal trauma history and
      completed a Human Trafficking Myths Scale. Results indicated that gender and
      human trafficking myth acceptance, but not sexual trauma history, were
      significantly related to participants' belief of the sex-trafficking scenario and
      their perception of the victim's responsibility. Potential implications and
      directions for future research are discussed. 

PMID- 25389190
TI  - High Immunoglobulin A Levels Mediate the Association Between High Anger
      Expression and Low Somatic Symptoms in Intimate Partner Violence Perpetrators.
AB  - It has been hypothesized that anger expression may be associated with increased
      salivary immunoglobulin A (sIgA) levels, which is associated with decreased
      somatic symptoms, and therefore anger expression may be associated with reduced
      somatic symptoms in intimate partner violence (IPV) perpetrators. This study
      tested the potential mediating effect of sIgA levels on the relationship between
      anger expression and respiratory and gastrointestinal symptoms in IPV
      perpetrators and non-violent controls. The sample consisted of IPV perpetrators
      (n = 19) and controls (n = 21). Saliva samples were collected for assessing sIgA
      levels. The State-Trait Anger Expression Inventory-2 was used to assess anger
      expression and the Revised version of the Somatic Symptoms Scale developed by
      Sandin and Chorot to measure somatic symptoms. High anger expression was
      associated with low levels of respiratory and gastrointestinal symptoms in IPV
      perpetrators mediated through high sIgA levels but the same was not true for non
      violent controls. This finding supports the hypothesis that for IPV perpetrators,
      anger expression may be physiologically and psychologically rewarding. Future
      research examining other immunological parameters is needed to further test this
      hypothesis. Such effort may illuminate why some IPV perpetrators continue to use
      violence against their partners.

PMID- 25389191
TI  - Moderating Effect of Negative Peer Group Climate on the Relation Between Men's
      Locus of Control and Aggression Toward Intimate Partners.
AB  - The present study sought to examine the interactive effects of an external locus
      of control and interaction in a negative peer group climate on men's perpetration
      of physical aggression and infliction of injury toward their female intimate
      partners. Participants were 206 heterosexual males recruited from the metro
      Atlanta community who completed self-report measures of external locus of
      control, involvement in a negative peer group climate, and physical aggression
      and infliction of injury against intimate partners during the past 12 months.
      Negative peer group climate was conceptualized as a peer group that displays
      behavior which may instigate aggressive norms, attitudes, and behaviors. Results
      indicated that men with an external locus of control were more likely to
      perpetrate physical aggression toward and inflict injury on their intimate
      partners if they reported high, but not low, involvement in a negative peer group
      climate. These results extend current research suggesting external locus of
      control as a risk factor for intimate partner aggression by highlighting the
      impact of negative peer groups. Implications and future intervention research are
      discussed. 

PMID- 25389192
TI  - Affective Dispositions and PTSD Symptom Clusters in Female Interpersonal Trauma
      Survivors.
AB  - Interpersonal trauma (IPT) against women can have dire psychological consequences
      including persistent maladaptive changes in the subjective experience of affect.
      Contemporary literature has firmly established heightened negative affect (NA) as
      a risk and maintenance factor for posttraumatic stress disorder (PTSD). However,
      the relationship between NA and PTSD symptoms is not well understood within IPT
      survivors, the majority of whom are female, as much of this research has focused
      on combat veterans. In addition, the connection between positive affect (PA) and
      PTSD symptoms has yet to be examined. With increased emphasis on "negative
      alterations in cognitions and mood . . ." as an independent symptom cluster of
      PTSD in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM
      5), understanding the relationship between self-reported affectivity and the
      classic PTSD symptom clusters may be increasingly useful in differentiating
      symptom presentations of trauma-related psychopathology. The current study
      directly compared self-reported trait NA and PA with total severity and frequency
      cluster scores from the Clinician-Administered PTSD Scale (CAPS) in 54 female
      survivors of IPT who met criteria for PTSD. Results identify NA (but not PA) as a
      consistent predictor of total PTSD symptoms and, specifically, re-experiencing
      symptoms. 

PMID- 25389193
TI  - The Process of Reporting and Receiving Support Following Exposure to Intimate
      Partner Violence During Childhood.
AB  - While a significant body of research suggests that exposure to intimate partner
      violence (IPV) during childhood has severe and long-lasting consequences, little
      is known about how children cope with witnessing IPV, including who they tell
      about the violence, whether they receive support after disclosing, and the
      association between childhood disclosure and adulthood mental health. The current
      study examines these issues in 703 Swedish young adults who endorsed witnessing
      IPV during childhood. In this sample, 57% reported that they had ever confided in
      someone about the witnessed violence. The primary reason given for not disclosing
      was the belief that no one could do anything about it, which was endorsed by 41%
      of the young adults who kept the violence concealed. Individuals who disclosed
      the violence were most likely to tell a friend and least likely to use an
      anonymous hotline. Young adults with higher levels of depression were less likely
      to have disclosed IPV during their childhood. Individuals' use of formal
      reporting outlets was endorsed infrequently, with only 5.2% recalling that they
      had personally reported the violence or someone else had reported it on their
      behalf. If such reports were filed, it was most likely to the police. These
      formal reports typically resulted in participants feeling that the problem
      continued anyway or that they were believed, but no changes were made. Given the
      infrequent use of formal reporting services, results suggest that for this
      sample, reporting outlets for IPV exposure may be underutilized and may not be
      perceived as beneficial. 

PMID- 25389194
TI  - Transphobic Murders in Italy: An Overview of Homicides in Milan (Italy) in the
      Past Two Decades (1993-2012).
AB  - In Europe, 71 murders resulting in the death of transgendered persons were
      reported between 2008 and 2013, 20 of which perpetrated in Italy, the second
      highest rate in Europe after Turkey. We retrospectively analyzed the homicides of
      transgender people recorded at the Medicolegal Bureau in Milan from January 1993
      to December 2012. First we considered the sociodemographic data of 20 victims and
      the circumstantial details of their deaths, then we examined the data related to
      the cause of death from the autopsy reports. Our data show that victims are
      mostly immigrants, biological males presenting with a feminine attire and with
      varying degrees of feminization. The large majority of the victims were sex
      workers from South America. As for murderers, they were unknown in 7 cases (35%);
      all the 13 murderers identified were males, aged between 17 and 63 (M age = 31
      years). In 38% of the cases, the murderer was the victim's current or former
      partner. For half of the homicides, it was possible to identify at least one
      primary indicator of lesbian, gay, bisexual, and transgender (LGBT) hate crime.
      Our findings call for the need to make explicit in Italian legislation that a
      crime perpetrated on the ground of sexual orientation and gender identity
      constitutes a hate crime. 

PMID- 25389195
TI  - Predicting Risk Factors for Intimate Partner Violence Among Post-9/11 College
      Student Veterans.
AB  - The current conflicts in Afghanistan and Iraq present unique risk factors for
      military personnel that increase the likelihood of psychological distress and
      concomitant consequences related to trauma. Several studies have found that the
      stress brought about by financial difficulties, unemployment, and the need to
      renegotiate roles and responsibilities with spouses following discharge increases
      the likelihood of relationship strain and even intimate partner violence in the
      veteran population. This study was undertaken to determine the challenges related
      to maintaining healthy relationships for college student veterans who have served
      in the armed forces since September 11, 2001. Psychological distress, substance
      use, and hypermasculine attitudes were explored as risk factors for intimate
      violence. Social support was found to be a protective buffer against
      psychological aggression. However, approximately a third of college student
      veterans reported low social support along with symptoms of distress, placing
      them at elevated risk of partner abuse. The current article explores models for
      predicting risk of perpetrating aggression in college student veterans and
      concludes that culturally tailored programs and services are needed.

PMID- 25389196
TI  - Aggression Replacement Training for Violent Young Men in a Forensic Psychiatric
      Outpatient Clinic.
AB  - The effects of Aggression Replacement Training (ART) were explored in a group of
      Dutch violent young men aged 16 to 21 years, who were obliged by the court to
      follow a treatment program in a forensic psychiatric outpatient clinic. To
      evaluate the training, patients completed a set of self-report questionnaires at
      three moments in time: at intake/before a waiting period, after the waiting
      period/before the training, and after the training. During the waiting period,
      the patients did not change on most measures, although they displayed a
      significant increase in anger. The patients who completed the therapy scored
      significantly lower on psychopathy than the patients who dropped out. The
      training produced significant decreases in physical aggression and social anxiety
      and showed trends toward a decline in self-reported hostility, general
      aggression, and anger. After the training, the patients scored comparably with a
      reference group on measures of hostility and aggressive behavior. Altogether,
      these results provide tentative support for the efficacy of the ART for violent
      young men referred to forensic psychiatric outpatient settings. 

PMID- 25389197
TI  - Age related differences in the validity of the OMNI perceived exertion scale
      during lifestyle activities.
AB  - PURPOSE: The OMNI perceived exertion scale was developed for children to report
      perceived effort while performing physical activity; however no studies have
      formally examined age-related differences in validity. This study evaluated the
      validity of the OMNI-RPE in 4 age groups performing a range of lifestyle
      activities. METHODS: 206 participants were stratified into four age groups: 6-8
      years (n = 42), 9-10 years (n = 46), 11-12 years (n = 47), and 13-15 years (n =
      71). Heart rate and VO2 were measured during 11 activity trials ranging in
      intensity from sedentary to vigorous. After each trial, participants reported
      effort from the OMNI walk/run scale. Concurrent validity was assessed by
      calculating within-subject correlations between OMNI ratings and the two
      physiological indices. RESULTS: The average correlation between OMNI ratings and
      VO2 was 0.67, 0.77, 0.85, and 0.87 for the 6-8, 9-10, 11-12 and 13-15 y age
      groups, respectively. CONCLUSION: The OMNI RPE scale demonstrated fair to good
      evidence of validity across a range of lifestyle activities among 6- to 15-year
      old children. The validity of the scale appears to be developmentally related
      with RPE reports closely reflecting physiological responses among children older
      than 8 years.

PMID- 25389198
TI  - An objective evaluation of gaze tracking in Humphrey perimetry and the relation
      with the reproducibility of visual fields: a pilot study in glaucoma.
AB  - PURPOSE: To develop a novel method to evaluate gaze tracking (GT) results and to
      examine their relationship with test-retest reproducibility of visual field (VF)
      measurements. METHODS: Subjects comprised of 42 eyes of 42 glaucoma patients.
      Vision fixation during VF tests with the Humphrey Field Analyzer was evaluated
      using the gaze fixation line chart at the bottom of the VF printout. We defined
      some GT parameters as follows: average tracking failure frequency per stimulus
      (TFF), average frequency of eye movements between 1 degrees  and 2 degrees , 3
      degrees  and 5 degrees , and more than 6 degrees . Humphrey VFs (24-2 and 10-2
      Swedish Interactive Threshold Algorithm [SITA] standard) were prospectively
      examined twice within a period of 3 months in 42 glaucoma patients. Mean absolute
      variability of total deviation (TD) values in the test-retest VFs was measured
      and its relationship to fixation losses (FLs), false positives (FPs), false
      negatives (FNs), mean deviation (MD), and pattern standard deviation (PSD) was
      investigated using the corrected Akaike Information Criterion (AICc) from linear
      modeling. RESULTS: The best model to predict test-retest variability in the 24-2
      VF included PSD, TFF, and FNs as dependent variables, while the best model for
      the 10-2 VF included PSD and average frequency of eye movements between 3 degrees
      and 5 degrees  (P < 0.05 for all coefficients). CONCLUSIONS: Gaze tracking
      parameters are closely related to the reproducibility of VF results, and it would
      be beneficial to objectively use these parameters when estimating the reliability
      of VF tests.

PMID- 25389199
TI  - Cell surface markers of functional phenotypic corneal endothelial cells.
AB  - PURPOSE: Cultured human corneal endothelial cells (HCECs) are anticipated to
      serve as an alternative to donor corneas for the treatment of corneal endothelial
      dysfunction. However, corneal endothelial cells (CECs) tend to exhibit
      fibroblastic transformation, thereby losing their functional phenotype when
      cultured. The purpose of this study was to investigate the usefulness of surface
      markers of CECs displaying fibroblastic phenotypes as a means of cell
      characterization. METHODS: The expression levels of 242 cell surface antigens
      were screened in cultured human and monkey CECs using flow cytometry. An
      expression intensity ratio of nonfibroblastic/fibroblastic CECs > 2 and of
      fibroblastic/nonfibroblastic CECs > 2 were selected as indicating nonfibroblastic
      and fibroblastic markers, respectively. Nonfibroblastic and fibroblastic CECs
      were mixed, and CD73-positive and -negative cells were sorted using flow
      cytometry and further cultured. The functional phenotype of the sorted cells was
      evaluated according to morphology and the expression of function-related
      (Na(+)/K(+)-ATPase and ZO-1) and fibroblastic (type I collagen and fibronectin)
      markers. RESULTS: Flow cytometry analysis demonstrated that CD98, CD166, and
      CD340 are elevated in HCECs of nonfibroblastic phenotype, while CD9, CD49e, CD44,
      and CD73 are markers of fibroblastic phenotype HCECs. The CECs that sorted as
      CD73-negative exhibited normal hexagonal morphology and expressed functional
      markers, whereas CECs that sorted as CD73-positive exhibited the fibroblastic
      phenotype. CONCLUSIONS: These markers will be useful for quality control to
      characterize the phenotype of cells destined for tissue engineering-based
      therapy. In addition, this selection protocol will provide a novel method for
      purification of functional cells.

PMID- 25389200
TI  - Physical activity and the 15-year incidence of age-related macular degeneration.
AB  - PURPOSE: There is uncertainty in the published literature as to whether physical
      activity should be advocated for age-related macular degeneration (AMD)
      prevention. We aimed to assess prospectively the association between physical
      activity and the 15-year incidence of AMD in older adults. METHODS: We assessed
      AMD from retinal photographs. Participants provided details of walking exercise
      and the performance of moderate or vigorous activities, which were used to
      calculate metabolic equivalents (METs). RESULTS: After adjusting for age, adults
      aged >= 75 years in the highest tertile (the most physically active) compared to
      those in the lowest tertile (least physically active) were 79% less likely to
      have incident late AMD over the 15 years (odds ratio [OR], 0.21; 95% confidence
      intervals [CI], 0.05-0.95). However, after further adjusting for sex, body mass
      index, smoking, fish consumption, and white cell count, this association was no
      longer statistically significant (OR, 0.26; 95% CI, 0.06-1.28). Significant
      associations were not found in those aged <75 or with the 15-year cumulative
      incidence of early AMD. CONCLUSIONS: Physical activity did not influence the risk
      of AMD over 15 years in older adults, independent of diet, smoking, white cell
      count, and body mass index.

PMID- 25389201
TI  - Effects of strabismic amblyopia and strabismus without amblyopia on visuomotor
      behavior: III. Temporal eye-hand coordination during reaching.
AB  - PURPOSE: To examine the effects of strabismic amblyopia and strabismus only,
      without amblyopia, on the temporal patterns of eye-hand coordination during both
      the planning and execution stages of visually-guided reaching. METHODS: Forty-six
      adults (16 with strabismic amblyopia, 14 with strabismus only, and 16 visually
      normal) executed reach-to-touch movements toward targets presented randomly 5
      degrees  or 10 degrees  to the left or right of central fixation. Viewing
      conditions were binocular, monocular viewing with the amblyopic eye, and
      monocular viewing with the fellow eye (dominant and nondominant viewing for
      participants without amblyopia). Temporal coordination between eye and hand
      movements was examined during reach planning (interval between the initiation of
      saccade and reaching, i.e., saccade-to-reach planning interval) and reach
      execution (interval between the initiation of saccade and reach peak velocity
      [PV], i.e., saccade-to-reach PV interval). The frequency and dynamics of
      secondary reach-related saccades were also examined. RESULTS: The temporal
      patterns of eye-hand coordination prior to reach initiation were comparable among
      participants with strabismic amblyopia, strabismus only, and visually normal
      adults. However, the reach acceleration phase of participants with strabismic
      amblyopia and those with strabismus only were longer following target fixation
      (saccade-to-reach PV interval) than that of visually normal participants (P <
      0.05). This effect was evident under all viewing conditions. The saccade-to-reach
      planning interval and the saccade-to-reach PV interval were not significantly
      different among participants with amblyopia with different levels of acuity and
      stereo acuity loss. Participants with strabismic amblyopia and strabismus only
      initiated secondary reach-related saccades significantly more frequently than
      visually normal participants. The amplitude and peak velocity of these saccades
      were significantly greater during amblyopic eye viewing in participants with
      amblyopia who also had negative stereopsis. CONCLUSIONS: Adults with strabismic
      amblyopia and strabismus only showed an altered pattern of temporal eye-hand
      coordination during the reach acceleration phase, which might affect their
      ability to modify reach trajectory using early online control. Secondary reach
      related saccades may provide a compensatory mechanism with which to facilitate
      the late online control process in order to ensure relatively good reaching
      performance during binocular and fellow eye viewing.

PMID- 25389202
TI  - Objective evaluation of the degree of pigmentation in human induced pluripotent
      stem cell-derived RPE.
AB  - PURPOSE: For the transplantation of human induced pluripotent stem cell-derived
      retinal pigment epithelium (hiPSC-RPE), determination of the maturation status of
      these cells is essential, and the degree of pigmentation (dPG) can serve as a
      good indicator of this status. The aim of this study was to establish a method of
      objectively and quantitatively evaluating the dPG of hiPSC-RPE. METHODS: Two
      observers determined the dPG subjectively by observing recorded images of hiPSC
      RPE as follows: the dPG of a single cell was classified into three different
      pigmentation stages, and the overall dPG was compared between two cell groups to
      identify the group with the higher dPG. The kappa statistic was applied to assess
      interobserver reproducibility. Next, the dPG of single cells and cell groups was
      objectively determined by the lightness of the hue, saturation, and value (HSL)
      color space, and the correlation between the subjective evaluation and time
      dependent change in the objective dPG of hiPSC-RPE was investigated. RESULTS: The
      kappa statistic was 0.88 and 0.81 in the single-cell and cell-group observations,
      respectively. The objective dPG of single cells and cell groups was highly
      correlated with the subjective dPG. However, the observers were occasionally
      unable to subjectively determine the group with the higher dPG. The objective dPG
      increased in a time-dependent manner. CONCLUSIONS: The lightness of the HSL color
      space can be used to objectively and quantitatively evaluate the dPG of hiPSC-RPE
      in culture. The objective evaluation was consistent and was able to better
      identify small differences than subjective evaluation.

PMID- 25389204
TI  - Kinematics and Kinetics of Maximum Running Speed in Youth Across Maturity.
AB  - Sprinting is an important physical capacity and the development of sprint ability
      can take place throughout the athlete's growth. The purpose of this study
      therefore was to determine if the kinematics and kinetics associated with maximum
      sprint velocity differs in male youth participants of different maturity status
      (pre, mid- and postpeak height velocity (PHV)) and if maximum sprint velocity is
      determined by age, maturity or individual body size measurement. Participants (n
      = 74) sprinted over 30 meters on a nonmotorized treadmill and the fastest four
      consecutive steps were analyzed. Pre-PHV participants were found to differ
      significantly (p < .05) to mid- and post-PHV participants in speed, step length,
      step frequency, vertical and horizontal force, and horizontal power (~8-78%).
      However, only relative vertical force and speed differed significantly between
      mid and post-PHV groups. The greatest average percent change in kinetics and
      kinematics was observed from pre- to mid-PHV (37.8%) compared with mid- to post-
      PHV groups (11.6%). When maturity offset was entered as a covariate, there was no
      significant difference in velocity between the three groups. However, all groups
      were significantly different from each other when age was chosen as the
      covariate. The two best predictors of maximal velocity within each maturity group
      were power and horizontal force (R2 = 97-99%) indicating the importance of
      horizontal force application while sprinting. Finally, maturity explained 83% of
      maximal velocity across all groups. 

PMID- 25389203
TI  - Age- and race-related differences in human scleral material properties.
AB  - PURPOSE: We tested the hypothesis that there are age- and race-related
      differences in posterior scleral material properties, using eyes from human
      donors of European (20-90 years old, n = 40 eyes) and African (23-74 years old, n
      = 22 eyes) descent. METHODS: Inflation tests on posterior scleral shells were
      performed while full-field, three-dimensional displacements were recorded using
      laser speckle interferometry. Scleral material properties were fit to each eye
      using a microstructure-based constitutive formulation that incorporates the
      collagen fibril crimp and the local anisotropic collagen architecture. The
      effects of age and race were estimated using Generalized Estimating Equations,
      while accounting for intradonor correlations. RESULTS: The shear modulus
      significantly increased (P = 0.038) and collagen fibril crimp angle significantly
      decreased with age (P = 0.002). Donors of African descent exhibited a
      significantly higher shear modulus (P = 0.019) and showed evidence of a smaller
      collagen fibril crimp angle (P = 0.057) compared to donors of European descent.
      The in-plane strains in the peripapillary sclera were significantly lower with
      age (P < 0.015) and African ancestry (P < 0.015). CONCLUSIONS: The age- and race
      related differences in scleral material properties result in a loss of scleral
      compliance due to a higher shear stiffness and a lower level of stretch at which
      the collagen fibrils uncrimp. The loss of compliance should lead to larger high
      frequency IOP fluctuations and changes in the optic nerve head (ONH)
      biomechanical response in the elderly and in persons of African ancestry, and may
      contribute to the higher susceptibility to glaucoma in these at-risk populations.

PMID- 25389205
TI  - The evolutionary history of termites as inferred from 66 mitochondrial genomes.
AB  - Termites have colonized many habitats and are among the most abundant animals in
      tropical ecosystems, which they modify considerably through their actions. The
      timing of their rise in abundance and of the dispersal events that gave rise to
      modern termite lineages is not well understood. To shed light on termite origins
      and diversification, we sequenced the mitochondrial genome of 48 termite species
      and combined them with 18 previously sequenced termite mitochondrial genomes for
      phylogenetic and molecular clock analyses using multiple fossil calibrations. The
      66 genomes represent most major clades of termites. Unlike previous phylogenetic
      studies based on fewer molecular data, our phylogenetic tree is fully resolved
      for the lower termites. The phylogenetic positions of Macrotermitinae and
      Apicotermitinae are also resolved as the basal groups in the higher termites, but
      in the crown termitid groups, including Termitinae + Syntermitinae +
      Nasutitermitinae + Cubitermitinae, the position of some nodes remains uncertain.
      Our molecular clock tree indicates that the lineages leading to termites and
      Cryptocercus roaches diverged 170 Ma (153-196 Ma 95% confidence interval [CI]),
      that modern Termitidae arose 54 Ma (46-66 Ma 95% CI), and that the crown termitid
      group arose 40 Ma (35-49 Ma 95% CI). This indicates that the distribution of
      basal termite clades was influenced by the final stages of the breakup of
      Pangaea. Our inference of ancestral geographic ranges shows that the Termitidae,
      which includes more than 75% of extant termite species, most likely originated in
      Africa or Asia, and acquired their pantropical distribution after a series of
      dispersal and subsequent diversification events. 

PMID- 25389207
TI  - Mutational signatures indicative of environmental stress in bacteria.
AB  - Evolutionary innovations are dependent on mutations. Mutation rates are increased
      by adverse conditions in the laboratory, but there is no evidence that stressful
      environments that do not directly impact on DNA leave a mutational imprint on
      extant genomes. Mutational spectra in the laboratory are normally determined with
      unstressed cells but are unavailable with stressed bacteria. To by-pass problems
      with viability, selection effects, and growth rate differences due to stressful
      environments, in this study we used a set of genetically engineered strains to
      identify the mutational spectrum associated with nutritional stress. The strain
      set members each had a fixed level of the master regulator protein, RpoS, which
      controls the general stress response of Escherichia coli. By assessing mutations
      in cycA gene from 485 cycloserine resistant mutants collected from as many
      independent cultures with three distinct perceived stress (RpoS) levels, we were
      able establish a dose-dependent relationship between stress and mutational
      spectra. The altered mutational patterns included base pair substitutions, single
      base pair indels, longer indels, and transpositions of different insertion
      sequences. The mutational spectrum of low-RpoS cells closely matches the genome
      wide spectrum previously generated in laboratory environments, while the spectra
      of high RpoS, high perceived stress cells more closely matches spectra found in
      comparisons of extant genomes. Our results offer an explanation of the uneven
      mutational profiles such as the transition-transversion biases observed in extant
      genomes and provide a framework for assessing the contribution of stress-induced
      mutagenesis to evolutionary transitions and the mutational emergence of
      antibiotic resistance and disease states. 

PMID- 25389206
TI  - Accelerated diversification of nonhuman primate malarias in Southeast Asia:
      adaptive radiation or geographic speciation?
AB  - Although parasitic organisms are found worldwide, the relative importance of host
      specificity and geographic isolation for parasite speciation has been explored in
      only a few systems. Here, we study Plasmodium parasites known to infect Asian
      nonhuman primates, a monophyletic group that includes the lineage leading to the
      human parasite Plasmodium vivax and several species used as laboratory models in
      malaria research. We analyze the available data together with new samples from
      three sympatric primate species from Borneo: The Bornean orangutan and the long
      tailed and the pig-tailed macaques. We find several species of malaria parasites,
      including three putatively new species in this biodiversity hotspot. Among those
      newly discovered lineages, we report two sympatric parasites in orangutans. We
      find no differences in the sets of malaria species infecting each macaque species
      indicating that these species show no host specificity. Finally, phylogenetic
      analysis of these data suggests that the malaria parasites infecting Southeast
      Asian macaques and their relatives are speciating three to four times more
      rapidly than those with other mammalian hosts such as lemurs and African apes. We
      estimate that these events took place in approximately a 3-4-Ma period. Based on
      the genetic and phenotypic diversity of the macaque malarias, we hypothesize that
      the diversification of this group of parasites has been facilitated by the
      diversity, geographic distributions, and demographic histories of their primate
      hosts. 

PMID- 25389208
TI  - Energy expenditure in low active overweight and obese children at varying
      treadmill grades.
AB  - This study aimed to evaluate differences between low active overweight and obese
      children in terms of energy expenditure (EE), ventilation (VE), and cardiac
      response during graded submaximal treadmill testing at constant speed. METHODS:
      We categorized 20 children into two weight groups according to the International
      Obesity Task Force criteria: overweight (n = 10; age = 9.7 +/-1.34 years) and
      obese (n = 10; age = 10.4 +/- 1.4 years). Children performed treadmill testing at
      a constant speed (1.53 m.s-1) and increasing grade (0%, 4%, and 8%). every 3 min.
      RESULTS: The EE across all grades was significantly higher (p < .001) in obese
      than in overweight children. Differences at each grade disappeared when EE was
      adjusted by body mass; however, several differences remained when the EE was
      adjusted by fat-free mass or body surface area. The increase in EE with
      increasing grade was greater in obese children (effect size between 0% and 8% for
      EE was 1.17). BMI z-score and fat mass (kg) were the main predictors of EE
      (Kcal.min-1) and contributed to explaining 66%, 70%, and 83.4% of the variance in
      EE at 0%, 4% and 8% gradients respectively. CONCLUSION: We suggest that when
      assessing EE response to exercise, the degree of obesity should be taken into
      consideration.

PMID- 25389209
TI  - Acute Effects of Energy Deficit Induced by Moderate-Intensity Exercise or Energy
      Intake Restriction on Postprandial Lipemia in Healthy Girls.
AB  - Eleven healthy girls (mean +/- SD: age 12.1 +/- 0.6 years) completed three 2-day
      conditions in a counterbalanced, crossover design. On day 1, participants either
      walked at 60 (2)% peak oxygen uptake (energy deficit 1.55[0.20] MJ), restricted
      food energy intake (energy deficit 1.51[0.25] MJ) or rested. On day 2, capillary
      blood samples were taken at predetermined intervals throughout the 6.5 hr
      postprandial period before, and following, the ingestion of standardized
      breakfast and lunch meals. Fasting plasma triacylglycerol concentrations (TAG)
      was 29% and 13% lower than rest control in moderate-intensity exercise (effect
      size [ES] = 1.39, p = .01) and energy-intake restriction (ES = 0.57, p = .02)
      respectively; moderate-intensity exercise was 19% lower than energy-intake
      restriction (ES = 0.82, p = .06). The moderate-intensity exercise total area
      under the TAG versus time curve was 21% and 13% lower than rest control (ES =
      0.71, p = .004) and energy-intake restriction (ES = 0.39, p = .06) respectively;
      energy-intake restriction was marginally lower than rest control (-10%; ES =
      0.32, p = .12). An exercise-induced energy deficit elicited a greater reduction
      in fasting plasma TAG with a trend for a larger attenuation in postprandial
      plasma TAG than an isoenergetic diet-induced energy deficit in healthy girls. 

PMID- 25389210
TI  - Use of physical activity self-management strategies by high school students.
AB  - Teaching adolescents to use self-management strategies may be an effective
      approach to promoting lifelong physical activity (PA). However, the extent to
      which adolescents use self-management strategies and their impact on current PA
      have not been studied previously. The aims of this study were 1) to describe the
      prevalence of self-management strategy use in adolescents; and 2) to determine
      relationships between self-management strategy use, PA self-efficacy, and PA
      participation. 197 students completed questionnaires measuring use of self
      management strategies, self-efficacy, and PA behavior. The most prevalent self
      management strategies (>30%) were thinking about the benefits of PA, making PA
      more enjoyable, choosing activities that are convenient, setting aside time to do
      PA, and setting goals to do PA. Fewer than 10% reported rewarding oneself for PA,
      writing planned activities in a book or calendar, and keeping charts of PA. Use
      of self-management strategies was associated with increased self-efficacy (r =
      .47, p < .001) and higher levels of PA (r = .34 p < .001). A 1-unit difference in
      self-management strategy scores was associated with a ~fourfold increase in the
      probability of being active (OR = 3.7, 95% CI = 1.8-7.4). Although strongly
      associated with PA, a relatively small percentage of adolescents routinely use
      self-management strategies. 

PMID- 25389211
TI  - The UP4FUN Intervention Effect on Breaking Up Sedentary Time in 10- to 12-Year
      Old Belgian Children: The ENERGY-Project.
AB  - There are currently no studies available reporting intervention effects on
      breaking up children's sedentary time. This study examined the UP4FUN
      intervention effect on objectively measured number of breaks in sedentary time,
      number of sedentary bouts (>= 10 mins) and total and average amount of time spent
      in those sedentary bouts among 10- to 12-year-old Belgian children. The total
      sample included 354 children (mean age: 10.9 +/- 0.7 years; 59% girls) with valid
      ActiGraph accelerometer data at pre- and posttest. Only few and small
      intervention effects were found, namely on total time spent in sedentary bouts
      immediately after school hours (4-6PM; beta = -3.51mins) and on average time
      spent in sedentary bouts before school hours (6-8.30AM; beta = -4.83mins) and
      immediately after school hours in favor of children from intervention schools
      (beta = -2.71mins). Unexpectedly, girls from intervention schools decreased the
      number of breaks during school hours (8.30AM-4PM; beta = -23.45breaks) and
      increased the number of sedentary bouts on a weekend day (beta = +0.90bouts),
      whereas girls in control schools showed an increase in number of breaks and a
      decrease in number of bouts. In conclusion, UP4FUN did not have a consistent or
      substantial effect on breaking up children's sedentary time and these data
      suggest that more intensive and longer lasting interventions are needed. 

PMID- 25389212
TI  - Psychosocial Oncology Supports for Men: A Scoping Review and Recommendations.
AB  - Although men's cancer experiences have received limited attention within the
      field of psychosocial oncology, increasing attention is being devoted to the
      development and evaluation of men-centered programs. This scoping review
      describes this emergent body of literature, detailing the focus, participation,
      and impact of interventions designed to help men with cancer build illness
      specific knowledge, adapt to illness, manage side effects, distress, and
      uncertainty, sustain relationships, and more. Striving to build on existing
      knowledge, research gaps and opportunities are discussed, including a need for
      stronger methodologies, more tailored and targeted supports, attention to the
      experiences of men with nonprostate cancers, and the explicit integration of
      gender analyses in the research process. 

PMID- 25389213
TI  - Using FacebookTM to Recruit College-Age Men for a Human Papillomavirus Vaccine
      Trial.
AB  - College-age men were recruited using FacebookTM advertisements (ads), as well as
      traditional recruitment methods, for a randomized controlled trial to compare
      immunological responses to human papillomavirus vaccine administered in two
      dosing schedules. This study compares enrollees who were recruited through
      traditional recruitment methods versus social networking sites (SNSs), including
      Facebook. Potential participants were recruited using flyers posted on and off
      campus(es), and distributed at health fairs, classes, sporting, and other campus
      events; e-mails to students and student organizations; and print advertisements
      in student newspapers and on city buses. Facebook ads were displayed to users
      with specific age, geographic, and interest characteristics; ads were monitored
      daily to make adjustments to improve response. A total of 220 males, aged 18 to
      25 years enrolled between October 2010 and May 2011. The majority of participants
      (51%) reported print advertisements as the method by which they first heard about
      the study, followed by personal contact (29%) and Facebook or other SNSs (20%).
      The likelihood of a SNS being the source by which the participant first heard
      about the study compared with traditional methods was increased if the
      participant reported (a) being homosexual or bisexual or (b) posting daily
      updates on SNSs. Facebook and other SNSs are a viable recruitment strategy for
      reaching potential clinical trial participants among groups who typically use
      social media to stay connected with their friends and hard-to-reach groups such
      as young men who self-identify as homosexual or bisexual. 

PMID- 25389214
TI  - Body Image Avoidance, Body Dissatisfaction, and Eating Pathology: Is There a
      Difference Between Male Gym Users and Non-Gym Users?
AB  - With research highlighting the increasing prevalence and severity of body image
      and eating disturbances in males, particularly athletes and regular gymnasium
      users, the current study examined body image and eating disturbances in a sample
      of male gym users and non-gym users (N = 180). Based on previous research, it was
      predicted that male gym users would report greater body image disturbance (e.g.,
      body image avoidance and body dissatisfaction) and eating pathology, compared
      with non-gym users. Results of the study partially supported hypotheses,
      revealing body dissatisfaction and eating pathology were significantly increased
      in male gym users. However, no significant differences were observed in body
      image avoidance behaviors, though this is likely because of methodological
      limitations associated with psychometric measures selected. The study provides
      preliminary evidence that male gym users do experience subclinical eating and
      body image concerns, with some also experiencing clinically significant symptoms
      that could be precursors to the later development of an eating disorder. Results
      of the current study highlight the importance of educating key stakeholders
      within health and fitness centers, through community-based interventions, to
      increase awareness regarding male body image and eating disturbances. 

PMID- 25389215
TI  - Family Planning and Preconception Health Among Men in Their Mid-30s: Developing
      Indicators and Describing Need.
AB  - The Centers for Disease Control and Prevention and Healthy People 2020 call for
      improvements in meeting men's reproductive health needs but little is known about
      the proportion of men in need. This study describes men aged 35 to 39 in need of
      family planning and preconception care, demographic correlates of these needs,
      and contraception use among men in need of family planning. Using data from Wave
      4 (2008-2010) of the National Survey of Adolescent Males, men were classified in
      need of family planning and preconception care if they reported sex with a female
      in the last year and believed that they and their partner were fecund; the former
      included men who were neither intentionally pregnant nor intending future
      children and the latter included men intending future children. Men were
      classified as being in need of both if they reported multiple sex partners in the
      past year. About 40% of men aged 35 to 39 were in need of family planning and
      about 33% in need of preconception care with 12% in need of both. Current
      partner's age, current union type, and sexually transmitted infection health risk
      differentiated men in need of family planning and preconception care (all ps <
      .01) and participants' race/ethnicity further differentiated men in need of
      preconception care (p < .01). More than half of men in need of family planning
      reported none of the time current partner hormonal use (55%) or condom use (52%)
      during the past year. This study identified that many men in their mid-30s are in
      need of family planning or preconception care. 

PMID- 25389216
TI  - Correlates of Perceived HIV Prevalence and Associations With HIV Testing Behavior
      Among Men Who Have Sex With Men in the United States.
AB  - As the rate of HIV infection continues to rise among men who have sex with men
      (MSM) in the United States, a focus of current prevention efforts is to encourage
      frequent HIV testing. Although levels of lifetime testing are high, low levels of
      routine testing among MSM are concerning. Using data from an online sample of 768
      MSM, this article explores how perceptions of HIV prevalence are associated with
      HIV testing behavior. Ordinal logistic regression models were fitted to examine
      correlates of perceived prevalence, and binary logistic regression models were
      fitted to assess associations between perceived prevalence and HIV testing. The
      results indicate that perceptions of higher prevalence among more proximal
      reference groups such as friends and sex partners are associated with greater
      odds of HIV testing. Perceptions of HIV prevalence were nonuniform across the
      sample; these variations point to groups to target with strategic messaging and
      interventions to increase HIV testing among MSM. 

PMID- 25389217
TI  - Sedentary Time and Screen-Based Sedentary Behaviors of Children With a Chronic
      Disease.
AB  - The objectives of this study were to (i) assess sedentary time and prevalence of
      screen-based sedentary behaviors of children with a chronic disease and (ii)
      compare sedentary time and prevalence of screen-based sedentary behaviors to age-
      and sex-matched healthy controls. Sixty-five children (aged 6-18 years) with a
      chronic disease participated: survivors of a brain tumor, hemophilia, type 1
      diabetes mellitus, juvenile idiopathic arthritis, cystic fibrosis, and Crohn's
      disease. Twenty-nine of these participants were compared with age- and sex
      matched healthy controls. Sedentary time was measured objectively by an ActiGraph
      GT1M or GT3* accelerometer worn for 7 consecutive days and defined as less than
      100 counts per min. A questionnaire was used to assess screen-based sedentary
      behaviors. Children with a chronic disease engaged in an average of 10.2 +/- 1.4
      hr of sedentary time per day, which comprised 76.5 +/- 7.1% of average daily
      monitoring time. There were no differences between children with a chronic
      disease and controls in sedentary time (adjusted for wear time, p = .06) or in
      the prevalence of TV watching, and computer or video game usage for varying
      durations (p = .78, p = .39 and, p = .32 respectively). Children with a chronic
      disease, though relatively healthy, accumulate high levels of sedentary time,
      similar to those of their healthy peers. 

PMID- 25389218
TI  - LSD-assisted psychotherapy for anxiety associated with a life-threatening
      disease: a qualitative study of acute and sustained subjective effects.
AB  - OBJECTIVE: A recently published study showed the safety and efficacy of LSD
      assisted psychotherapy in patients with anxiety associated with life-threatening
      diseases. Participants of this study were included in a prospective follow-up.
      METHOD: 12 months after finishing LSD psychotherapy, 10 participants were tested
      for anxiety (STAI) and participated in a semi-structured interview. A Qualitative
      Content Analysis (QCA) was carried out on the interviews to elaborate about LSD
      effects and lasting psychological changes. RESULTS: None of the participants
      reported lasting adverse reactions. The significant benefits as measured with the
      STAI were sustained over a 12-month period. In the QCA participants consistently
      reported insightful, cathartic and interpersonal experiences, accompanied by a
      reduction in anxiety (77.8%) and a rise in quality of life (66.7%). Evaluations
      of subjective experiences suggest facilitated access to emotions, confrontation
      of previously unknown anxieties, worries, resources and intense emotional peak
      experiences a la Maslow as major psychological working mechanisms. The
      experiences created led to a restructuring of the person's emotional trust,
      situational understanding, habits and world view. CONCLUSIONS: LSD administered
      in a medically supervised psychotherapeutic setting can be safe and generate
      lasting benefits in patients with a life-threatening disease. Explanatory models
      for the therapeutic effects of LSD warrant further study.

PMID- 25389219
TI  - Considerations on the role of buprenorphine in recovery from heroin addiction
      from a UK perspective.
AB  - The United Kingdom Drug Strategy emphasises recovery as a key focus in the
      treatment of drug dependence. A framework for recovery is defined in the Recovery
      Orientated Drug Treatment report, written by an expert working group, and
      comprises four key phases: engagement and stabilisation, including the
      establishment of treatment goals; preparation for change, involving engagement in
      psychosocial and pharmacological interventions; active change, including
      detoxification and medical withdrawal; and completion, including interventions
      that strengthen community integration. A body of evidence supports the benefits
      of buprenorphine, a partial agonist at mu opioid receptors, in supporting
      individualised recovery based on this framework, specifically in relation to the
      potential for rapid stabilisation, flexibility to transition to other treatment
      options or achieve abstinence, effective blocking of on-top use of illicit drugs,
      the treatment of comorbidities through the minimisation of drug-drug
      interactions, and a good safety profile. In addition, the newer abuse-deterrent
      formulation of buprenorphine combined with the opioid antagonist naloxone is
      likely to strengthen recovery-orientated systems of care due to its potential to
      reduce misuse and diversion. Progress through the recovery journey and the
      ability to sustain recovery will depend on individual needs and goals and on the
      amount of recovery capital that individuals have developed. 

PMID- 25389220
TI  - Fluorescence lifetime for studying ophthalmic diseases in animal models.

PMID- 25389221
TI  - Health awareness and consequences of consanguineous marriages: a community-based
      study.
AB  - OBJECTIVES: This community-based study was done to assess the awareness of people
      regarding the ill effects of consanguinity and to observe its association with
      various sociodemographic variables and complications among children. METHODS:
      Houses were chosen by systematic random sampling method and any married person in
      each household was interviewed. RESULTS: Only 35 (18.7%) out of 187 participants
      were aware of health hazards associated with consanguineous marriages. The
      prevalence of consanguineous marriages was found to be 23 (12.3%). History of
      consanguineous marriage was seen significantly more among illiterates (P = .05)
      and respondents with parental history of consanguinity (P < .001). The mean age
      at marriage was found to be significantly lower among women married
      consanguineously (P = .05). Congenital anomalies (P = .02) and low birth weight
      (P = .05) was seen significantly more among children with parental history of
      consanguinity. CONCLUSION: Large-scale awareness campaigns are needed to address
      the ill effects of this seemingly innocuous cultural practice.

PMID- 25389222
TI  - Access to primary care services among the homeless: a synthesis of the literature
      using the equity of access to medical care framework.
AB  - OBJECTIVE: To identify barriers and facilitators to primary care access among the
      homeless using the Equity of Access to Medical Care Framework and to provide
      recommendations for medical and public health practitioners to improve health
      among this underserved population. METHODS: A quasi-systematic review of the
      literature was conducted using the PubMed, CINAHL, and PsycINFO databases. Study
      elements from articles in the final analysis were extracted and categorized into
      dimensions of access from the Framework. RESULTS: The review identified multiple
      barriers to primary care access for the homeless. This included lack of insurance
      coverage and competing priorities. Facilitators to access included tailored
      health care delivery systems and having a regular source of care. CONCLUSION:
      This review provides evidence that health policy initiatives, patient-centered
      care, and targeted interventions can assist with improving primary care access
      among the homeless.

PMID- 25389223
TI  - Nitroimidazo-oxazole compound DNDI-VL-2098: an orally effective preclinical drug
      candidate for the treatment of visceral leishmaniasis.
AB  - OBJECTIVES: The objective of this study was to identify a nitroimidazo-oxazole
      lead molecule for the treatment of visceral leishmaniasis (VL). METHODS: A
      library of 72 nitroimidazo-oxazoles was evaluated in vitro for their
      antileishmanial activity against luciferase-transfected DD8 amastigotes of
      Leishmania donovani. On the basis of their in vitro potency and pharmacokinetic
      properties, the promising compounds were tested in acute BALB/c mouse and chronic
      hamster models of VL via oral administration and efficacy was evaluated by
      microscopic counting of amastigotes after Giemsa staining. The best
      antileishmanial candidates (racemate DNDI-VL-2001) and its R enantiomer (DNDI-VL
      2098) were evaluated in vitro against a range of Leishmania strains. These
      candidates were further studied in a hamster model using various dose regimens.
      Cytokine and inducible nitric oxide synthase estimations by real-time PCR and
      nitric oxide generation by Griess assay were also carried out for DNDI-VL-2098.
      RESULTS: In vitro screening of nitroimidazo-oxazole compounds identified the
      racemate DNDI-VL-2001 (6-nitroimidazo-oxazole derivative) and its enantiomers as
      candidates for further evaluation in in vivo models of VL. DNDI-VL-2098 (IC50 of
      0.03 MUM for the DD8 strain) showed excellent in vivo activity in both mouse and
      hamster models, with an ED90 value of 3.7 and <25 mg/kg, respectively, and was
      also found to be very effective against high-grade infection in the hamster
      model. Our studies revealed that, along with leishmanicidal activity, DNDI-VL
      2098 was also capable of inducing host-protective immune cells to suppress
      Leishmania parasites in hamsters. CONCLUSIONS: These studies led to the
      identification of compound DNDI-VL-2098 as a preclinical candidate for further
      drug development as an oral treatment for VL.

PMID- 25389224
TI  - Four novel plasmids from Staphylococcus hyicus and CoNS that carry a variant of
      the spectinomycin resistance gene spd.

PMID- 25389225
TI  - Commentary on Vickers.

PMID- 25389226
TI  - Commentary on Vickers.

PMID- 25389227
TI  - Commentary on Vickers.

PMID- 25389228
TI  - Response from the author.

PMID- 25389229
TI  - Lower limb amputation in England: prevalence, regional variation and relationship
      with revascularisation, deprivation and risk factors. A retrospective review of
      hospital data.
AB  - OBJECTIVE: We describe the prevalence of major lower limb amputation across
      England and its relationship with revascularisation, patient demography and
      disease risk factors. DESIGN: Retrospective cohort study. SETTING: England 1
      April 2003 to 31 March 2009. PARTICIPANTS: Patients aged 50-84 years. MAIN
      OUTCOME MEASURES: Age standardised prevalence rates were calculated using
      Hospital Episode Statistics as the numerator with census data as the denominator.
      The outcome measure 'amputation with revascularisation' was created if an
      amputation could be linked with a revascularisation. Logistic regression
      determined the odds of having an amputation with a revascularisation across
      England. Regression was performed unadjusted and repeated after controlling for
      demographic (age, sex, social deprivation) and disease risk factors (diabetes,
      hypertension, coronary heart disease, cerebrovascular disease, smoking). RESULTS:
      There were 25,312 amputations and 136,215 revascularisations, and 7543 cases were
      linked. The prevalence rate per 100,000 (95% confidence intervals) for amputation
      was 26.3 (26.0-26.6) with rates significantly higher in Northern England (North:
      31.7; 31.0-32.3, Midlands: 26.0; 25.3-26.7, South: 23.1; 22.6-23.5). The
      revascularisation rate was 141.6 (140.8-142.3) with significantly higher rates
      again in Northern England (North: 182.1; 180.5-183.7, Midlands: 121.3; 119.8
      122.9, South 124.9; 123.9-125.8). The odds of having an amputation with a
      revascularisation remained significantly higher in the North (OR 1.22; 1.13-1.33)
      even after controlling demographic and disease risk factors. CONCLUSIONS: There
      is a North-South divide in England for both major lower limb amputation and
      revascularisation. The higher odds of having an amputation with a
      revascularisation in the North were not fully explained by greater levels of
      deprivation or disease risk factors.

PMID- 25389230
TI  - Under-reporting of conflicts of interest among trialists: a cross-sectional
      study.
AB  - OBJECTIVES: To determine the prevalence of conflicts of interest (COIs) among
      Danish physicians who are authors of clinical drug trial reports and determine
      the extent of undisclosed COIs in trial publications. DESIGN: Cross-sectional
      study. SETTING: The 100 most recent drug trial reports with at least one Danish
      non-industry employed physician author published in a journal adhering to the
      International Committee of Medical Journal Editors' (ICMJE) manuscript
      guidelines. For each article, two observers independently extracted trial
      characteristics and the authors' COIs. Disclosed COIs were compared to what was
      registered on the Danish Health and Medicines Authority's public disclosure list.
      PARTICIPANTS: Trial authors who are Danish physicians. MAIN OUTCOME MEASURES:
      Number of disclosed and undisclosed COIs. RESULTS: One observer screened 928
      articles and two observers assessed 120 articles for eligibility. The 100
      included trials were published from February 2011 to May 2013 and included 318
      Danish non-industry employed authors. Eighty-six of the 318 authors (27%)
      reported one or more COIs in the journal article. We found undisclosed COIs for
      40 of 318 authors (13%) related to the trial sponsor or manufacturer of trial
      drugs. Seventy-nine of 318 authors (25%) had undisclosed COIs related to
      competing companies manufacturing drugs for the same indication and 136 (43%) had
      undisclosed COIs with any drug manufacturer. CONCLUSIONS: Almost half of all
      authors had undisclosed COIs in clinical trials reported in journals adhering to
      the International Committee of Medical Journal Editors' manuscript guidelines.
      Self-declared COIs cannot be trusted, but public registries may assist editors in
      ensuring that more COIs are being reported.

PMID- 25389231
TI  - Explaining symptoms after negative tests: towards a rational explanation.

PMID- 25389232
TI  - Isolated Gastrocnemius Recession for Treatment of Insertional Achilles
      Tendinopathy: A Pilot Study.
AB  - INTRODUCTION: Many surgeries exist for treatment of insertional Achilles
      tendinopathy. Another surgical option to consider is an isolated gastrocnemius
      recession. Recent studies have demonstrated the success of a gastrocnemius
      recession for noninsertional Achilles tendinitis. We hypothesize that an isolated
      gastrocnemius recession can be a successful, effective, and less invasive surgery
      for patients with chronic insertional Achilles tendinopathy. MATERIALS AND
      METHODS: This article presents a retrospective review of one surgeon's results of
      11 patients (2010-2012), with an average age of 59 years who presented with
      chronic insertional Achilles tendinopathy. Gastrocnemius recessions, either
      endoscopic or open, were performed after an average of 6.2 months of conservative
      treatment. All patients' radiographs were reviewed preoperatively for any
      calcaneal spurs and divided into groups accordingly. Average follow-up time
      postoperatively was 13.8 months. Plantarflexion strength, equinus deformity, as
      well as the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot
      instrument was assessed. RESULTS: In all, 10/11 (91%) patients had high patient
      satisfaction, pain relief, no residual equinus deformity, loss in muscle strength
      and returned to regular activities successfully at 1-year follow up. All patients
      and groups had significant improvement in AOFAS scores. The median postoperative
      AOFAS score was 94.8. All patients and patient groups had significant improvement
      pre- to postoperatively. Patients without spurs appear to do better than patients
      with spurs. One patient developed recurrence of insertional heel pain and equinus
      deformity. Other complications included 2 sural nerve parasthesias, which
      resolved. CONCLUSION: An isolated gastrocnemius recession for chronic insertional
      Achilles tendinopathy can provide high satisfaction, pain relief, and a faster
      recovery period with few or no complications. LEVELS OF EVIDENCE: Therapeutic,
      Level IV: Case series.

PMID- 25389233
TI  - Altered glycosylation of complexed native IgG molecules is associated with
      disease activity of systemic lupus erythematosus.
AB  - In addition to the redundancy of the receptors for the Fc portion of
      immunoglobulins, glycans result in potential ligands for a plethora of lectin
      receptors found in immune effector cells. Here we analysed the exposure of
      glycans containing fucosyl residues and the fucosylated tri-mannose N-type core
      by complexed native IgG in longitudinal serum samples of well-characterized
      patients with systemic lupus erythematosus. Consecutive serum samples of a cohort
      of 15 patients with systemic lupus erythematosus during periods of increased
      disease activity and remission were analysed. All patients fulfilled the 1982
      American College of Rheumatology classification criteria. Sera of 15 sex- and age
      matched normal healthy blood donors served as controls. The levels and type of
      glycosylation of complexed random IgG was measured with lectin enzyme
      immunosorbent assays. After specifically gathering IgG complexes from sera,
      biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were
      employed to detect IgG-associated fucosyl residues and the fucosylated tri
      mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA,
      C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune
      complex constituents. We studied associations of the glycan of complexed IgG and
      disease activity according to the physician's global assessment of disease
      activity and the systemic lupus erythematosus disease activity index 2000
      documented at the moment of blood taking. Our results showed significantly higher
      levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites
      exposed on IgG complexes of patients with systemic lupus erythematosus than on
      those of normal healthy blood donors. Disease activity in systemic lupus
      erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive
      fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia
      lectin-reactivity were found in samples taken during the highest activity of
      systemic lupus erythematosus. Our results show that native circulating IgG
      complexes from active systemic lupus erythematosus patients expose fucosyl
      residues and their glycan core is accessible to soluble lectins. Two putative
      mechanisms may contribute to the increased exposure of these glycans: (1) the
      canonical N-glycosylation site of the IgG-CH2 domain; (2) an IgG binding non-IgG
      molecule, like complement or C-reactive protein. In both cases the complexed IgG
      may be alternatively targeted to lectin receptors of effector cells, e.g.
      dendritic cells. 

PMID- 25389234
TI  - Postpartum depression in refugee and asylum-seeking women in Canada: A critical
      health psychology perspective.
AB  - Canada has one of the world's largest refugee resettlement programs in the world.
      Just over 48 percent of Canadian refugees are women, with many of them of
      childbearing age and pregnant. Refugee and asylum-seeking women in Canada face a
      five times greater risk of developing postpartum depression than Canadian-born
      women. Mainstream psychological approaches to postpartum depression emphasize
      individual-level risk factors (e.g. hormones, thoughts, emotions) and
      individualized treatments (e.g. psychotherapy, medication). This
      conceptualization is problematic when applied to refugee and asylum-seeking women
      because it fails to acknowledge the migrant experience and the unique set of
      circumstances from which these women have come. The present theoretical article
      explores some of the consequences of applying this psychiatric label to the
      distress experienced by refugee and asylum-seeking women and presents an
      alternative way of conceptualizing and alleviating this distress.

PMID- 25389235
TI  - The language of sedation in end-of-life care: The ethical reasoning of care
      providers in three countries.
AB  - The application of ethically controversial medical procedures may differ from one
      place to another. Drawing on a keyword and text-mining analysis of 156 interviews
      with doctors and nurses involved in end-of-life care ('care providers'),
      differences between countries in care providers' ethical rationales for the use
      of sedation are reported. In the United Kingdom, an emphasis on titrating doses
      proportionately against symptoms is more likely, maintaining consciousness where
      possible. The potential harms of sedation are perceived to be the potential
      hastening of social as well as biological death. In Belgium and the Netherlands,
      although there is concern to distinguish the practice from euthanasia, rapid
      inducement of deep unconsciousness is more acceptable to care providers. This is
      often perceived to be a proportionate response to unbearable suffering in a
      context where there is also greater pressure to hasten dying from relatives and
      others. This means that sedation is more likely to be organised like euthanasia,
      as the end 'moment' is reached, and family farewells are organised before the
      patient is made unconscious for ever. Medical and nursing practices are partly
      responses to factors outside the place of care, such as legislation and public
      sentiment. Dutch guidelines for sedation largely tally with the practices
      prevalent in the Netherlands and Belgium, in contrast with those produced by the
      more international European Association for Palliative Care whose authors
      describe an ethical framework closer to that reportedly used by UK care
      providers. 

PMID- 25389236
TI  - A review of basic to clinical studies of irreversible electroporation therapy.
AB  - The use of irreversible electroporation (IRE) for cancer treatment has increased
      sharply over the past decade. As a nonthermal therapy, IRE offers several
      potential benefits over other focal therapies, which include 1) short treatment
      delivery time, 2) reduced collateral thermal injury, and 3) the ability to treat
      tumors adjacent to major blood vessels. These advantages have stimulated
      widespread interest in basic through clinical studies of IRE. For instance, many
      in vitro and in vivo studies now identify treatment planning protocols (IRE
      threshold, pulse parameters, etc.), electrode delivery (electrode design,
      placement, intraoperative imaging methods, etc.), injury evaluation (methods and
      timing), and treatment efficacy in different cancer models. Therefore, this study
      reviews the in vitro, translational, and clinical studies of IRE cancer therapy
      based on major experimental studies particularly within the past decade. Further,
      this study provides organized data and facts to assist further research,
      optimization, and clinical applications of IRE.

PMID- 25389237
TI  - Inertial sensor-based stride parameter calculation from gait sequences in
      geriatric patients.
AB  - A detailed and quantitative gait analysis can provide evidence of various gait
      impairments in elderly people. To provide an objective decision-making basis for
      gait analysis, simple applicable tests analyzing a high number of strides are
      required. A mobile gait analysis system, which is mounted on shoes, can fulfill
      these requirements. This paper presents a method for computing clinically
      relevant temporal and spatial gait parameters. Therefore, an accelerometer and a
      gyroscope were positioned laterally below each ankle joint. Temporal gait events
      were detected by searching for characteristic features in the signals. To
      calculate stride length, the gravity compensated accelerometer signal was double
      integrated, and sensor drift was modeled using a piece-wise defined linear
      function. The presented method was validated using GAITRite-based gait parameters
      from 101 patients (average age 82.1 years). Subjects performed a normal walking
      test with and without a wheeled walker. The parameters stride length and stride
      time showed a correlation of 0.93 and 0.95 between both systems. The absolute
      error of stride length was 6.26 cm on normal walking test. The developed system
      as well as the GAITRite showed an increased stride length, when using a four
      wheeled walker as walking aid. However, the walking aid interfered with the
      automated analysis of the GAITRite system, but not with the inertial sensor-based
      approach. In summary, an algorithm for the calculation of clinically relevant
      gait parameters derived from inertial sensors is applicable in the diagnostic
      workup and also during long-term monitoring approaches in the elderly population.

PMID- 25389238
TI  - An automated statistical shape model developmental pipeline: application to the
      human scapula and humerus.
AB  - This paper presents development of statistical shape models based on robust and
      rigid-groupwise registration followed by pointset nonrigid registration. The main
      advantages of the pipeline include automation in that the method does not rely on
      manual landmarks or a regionalization step; there is no bias in the choice of
      reference during the correspondence steps and the use of the probabilistic
      principal component analysis framework increases the domain of the shape
      variability. A comparison between the widely used expectation maximization
      iterative closest point algorithm and a recently reported groupwise method on
      publicly available data (hippocampus) using the well-known criteria of
      generality, specificity, and compactness is also presented. The proposed method
      gives similar values but the curves of generality and specificity are superior to
      those of the other two methods. Finally, the method is applied to the human
      scapula, which is a known difficult structure, and the human humerus. 

PMID- 25389239
TI  - Examination of Poststroke Alteration in Motor Unit Firing Behavior Using High
      Density Surface EMG Decomposition.
AB  - Recent advances in high-density surface electromyogram (EMG) decomposition have
      made it a feasible task to discriminate single motor unit activity from surface
      EMG interference patterns, thus providing a noninvasive approach for examination
      of motor unit control properties. In the current study, we applied high-density
      surface EMG recording and decomposition techniques to assess motor unit firing
      behavior alterations poststroke. Surface EMG signals were collected using a 64
      channel 2-D electrode array from the paretic and contralateral first dorsal
      interosseous (FDI) muscles of nine hemiparetic stroke subjects at different
      isometric discrete contraction levels between 2 to 10 N with a 2 N increment
      step. Motor unit firing rates were extracted through decomposition of the high
      density surface EMG signals and compared between paretic and contralateral
      muscles. Across the nine tested subjects, paretic FDI muscles showed decreased
      motor unit firing rates compared with contralateral muscles at different
      contraction levels. Regression analysis indicated a linear relation between the
      mean motor unit firing rate and the muscle contraction level for both paretic and
      contralateral muscles (p < 0.001), with the former demonstrating a lower
      increment rate (0.32 pulses per second (pps)/N) compared with the latter (0.67
      pps/N). The coefficient of variation (averaged over the contraction levels) of
      the motor unit firing rates for the paretic muscles (0.21 +/- 0.012) was
      significantly higher than for the contralateral muscles (0.17 +/- 0.014) (p <
      0.05). This study provides direct evidence of motor unit firing behavior
      alterations poststroke using surface EMG, which can be an important factor
      contributing to hemiparetic muscle weakness.

PMID- 25389241
TI  - Coded acquisition of high frame rate video.
AB  - High frame rate video (HFV) is an important investigational tool in sciences,
      engineering, and military. In ultrahigh speed imaging, the obtainable temporal,
      spatial, and spectral resolutions are limited by the sustainable throughput of in
      camera mass memory, lower bound of exposure time, and illumination conditions. To
      break these bottlenecks, we propose a new coded video acquisition framework that
      employs K >= 2 cameras, each of which makes random measurements of the video
      signal in both temporal and spatial domains. For each of the K cameras, this
      multicamera strategy greatly relaxes the stringent requirements in memory speed,
      shutter speed, and illumination strength. The recovery of HFV from these random
      measurements is posed and solved as a large-scale l1 minimization problem by
      exploiting joint temporal and spatial sparsities of the 3D signal. Three coded
      video acquisition techniques of varied tradeoffs between performance and hardware
      complexity are developed: 1) framewise coded acquisition; 2) pixelwise coded
      acquisition; and 3) columnwise-rowwise coded acquisition. The performances of
      these techniques are analyzed in relation to the sparsity of the underlying video
      signal. Simulations of these new HFV capture techniques are carried out and
      experimental results are reported.

PMID- 25389240
TI  - Significance of IMP3, nucleophosmin, and Ki-67 expression in papillary thyroid
      carcinoma.
AB  - The purpose of our study was to investigate the diagnostic value of expression of
      IMP3, nucleophosmin, and correlation of these markers with Ki-67 proliferation
      index in papillary thyroid carcinoma and benign neoplasms of thyroid gland. The
      aim was also to investigate whether there is a difference between papillary and
      micropapillary carcinomas with regard to clinicopathologic parameters beside
      IMP3, nucleophosmin, and Ki-67 proliferation index. It was concluded that IMP3
      and nucleophosmin cannot be a routine diagnostic marker for discrimination of
      papillary carcinomas and benign lesions. IMP3 positive staining was quite scarce
      in IMP3 positive papillary carcinomas although specifity of IMP3 is 100%. A
      statistically significant correlation was not detected between nucleophosmin, IMP
      3, and Ki-67 proliferation index. A statistically significant correlation was
      found between tumor size, lymphovascular embolism, and Ki-67 proliferation index.
      There was also significant correlation between tumor size and lymphovascular
      embolism. 

PMID- 25389242
TI  - Spatial correlation of high density EMG signals provides features robust to
      electrode number and shift in pattern recognition for myocontrol.
AB  - Research on pattern recognition for myoelectric control has usually focused on a
      small number of electromyography (EMG) channels because of better clinical
      acceptability and low computational load with respect to multi-channel EMG.
      However, recently, high density (HD) EMG technology has substantially improved,
      also in practical usability, and can thus be applied in myocontrol. HD EMG
      provides several closely spaced recordings in multiple locations over the skin
      surface. This study considered the use of HD EMG for controlling upper limb
      prostheses, based on pattern recognition. In general, robustness and reliability
      of classical pattern recognition systems are influenced by electrode shift in
      dons and doff, and by the presence of malfunctioning channels. The aim of this
      study is to propose a new approach to attenuate these issues. The HD EMG grid of
      electrodes is an ensemble of sensors that records data spatially correlated. The
      experimental variogram, which is a measure of the degree of spatial correlation,
      was used as feature for classification, contrary to previous approaches that are
      based on temporal or frequency features. The classification based on the
      variogram was tested on seven able-bodied subjects and one subject with
      amputation, for the classification of nine and seven classes, respectively. The
      performance of the proposed approach was comparable with the classic methods
      based on time-domain and autoregressive features (average classification accuracy
      over all methods ~ 95% for nine classes). However, the new spatial features
      demonstrated lower sensitivity to electrode shift ( +/- 1 cm) with respect to the
      classic features . When even just one channel was noisy, the classification
      accuracy dropped by ~ 10% for all methods. However, the new method could be
      applied without any retraining to a subset of high-quality channels whereas the
      classic methods require retraining when some channels are omitted. In conclusion,
      the new spatial feature space proposed in this study improved the robustness to
      electrode number and shift in myocontrol with respect to previous approaches.

PMID- 25389243
TI  - Spiking neural P systems with rules on synapses working in maximum spikes
      consumption strategy.
AB  - Spiking neural P systems (SN P systems, for short) are a class of parallel and
      distributed computation models inspired from the way the neurons process and
      communicate information by means of spikes. In this paper, we consider a new
      variant of SN P systems, where each synapse instead of neuron has a set of
      spiking rules, and the neurons contain only spikes; when the number of spikes in
      a given neuron is "recognized" by a rule on a synapse leaving from it, the rule
      is enabled; at a computation step, at most one enabled spiking rule is applied on
      a synapse, and k spikes are removed from a neuron if the maximum number of spikes
      that the applied spiking rules on the synapses starting from this neuron consume
      is k. The computation power of this variant of SN P systems is investigated.
      Specifically, we prove that such SN P systems can generate or accept any set of
      Turing computable natural numbers. This result gives an answer to an open problem
      formulated in Theor. Comput. Sci., vol. 529, pp. 82-95, 2014. 

PMID- 25389244
TI  - Adaptive Synchronization of Memristor-Based Neural Networks with Time-Varying
      Delays.
AB  - In this paper, adaptive synchronization of memristor-based neural networks (MNNs)
      with time-varying delays is investigated. The dynamical analysis here employs
      results from the theory of differential equations with discontinuous right-hand
      sides as introduced by Filippov. Sufficient conditions for the global
      synchronization of MNNs are established with a general adaptive controller. The
      update gain of the controller can be adjusted to control the synchronization
      speed. The obtained results complement and improve the previously known results.
      Finally, numerical simulations are carried out to demonstrate the effectiveness
      of the obtained results. 

PMID- 25389245
TI  - Learning With Mixed Hard/Soft Pointwise Constraints.
AB  - A learning paradigm is proposed and investigated, in which the classical
      framework of learning from examples is enhanced by the introduction of hard
      pointwise constraints, i.e., constraints imposed on a finite set of examples that
      cannot be violated. Such constraints arise, e.g., when requiring coherent
      decisions of classifiers acting on different views of the same pattern. The
      classical examples of supervised learning, which can be violated at the cost of
      some penalization (quantified by the choice of a suitable loss function) play the
      role of soft pointwise constraints. Constrained variational calculus is exploited
      to derive a representer theorem that provides a description of the functional
      structure of the optimal solution to the proposed learning paradigm. It is shown
      that such an optimal solution can be represented in terms of a set of support
      constraints, which generalize the concept of support vectors and open the doors
      to a novel learning paradigm, called support constraint machines. The general
      theory is applied to derive the representation of the optimal solution to the
      problem of learning from hard linear pointwise constraints combined with soft
      pointwise constraints induced by supervised examples. In some cases, closed-form
      optimal solutions are obtained. 

PMID- 25389246
TI  - Integration of Personalized Healthcare Pathways in an ICT Platform for Diabetes
      Managements: A Small-Scale Exploratory Study.
AB  - The availability of new tools able to support patient monitoring and personalized
      care may substantially improve the quality of chronic disease management. A
      personalized healthcare pathway (PHP) has been developed for diabetes disease
      management and integrated into an information and communication technology system
      to accomplish a shift from organization-centered care to patient-centered care. A
      small-scale exploratory study was conducted to test the platform. Preliminary
      results are presented that shed light on how the PHP influences system usage and
      performance outcomes. 

PMID- 25389247
TI  - Using Boolean Logic Modeling of Gene Regulatory Networks to Exploit the Links
      Between Cancer and Metabolism for Therapeutic Purposes.
AB  - The uncontrolled cell proliferation that is characteristically associated with
      cancer is usually accompanied by alterations in the genome and cell metabolism.
      Indeed, the phenomenon of cancer cells metabolizing glucose using a less
      efficient anaerobic process even in the presence of normal oxygen levels, termed
      the Warburg effect, is currently considered to be one of the hallmarks of cancer.
      Diabetes, much like cancer, is defined by significant metabolic changes. Recent
      epidemiological studies have shown that diabetes patients treated with the
      antidiabetic drug Metformin have significantly lowered risk of cancer as compared
      to patients treated with other antidiabetic drugs. We utilize a Boolean logic
      model of the pathways commonly mutated in cancer to not only investigate the
      efficacy of Metformin for cancer therapeutic purposes but also demonstrate how
      Metformin in concert with other cancer drugs could provide better and less toxic
      clinical outcomes as compared to using cancer drugs alone. 

PMID- 25389248
TI  - Skin Temperature Prediction in Lower Limb Prostheses.
AB  - Increased temperature and perspiration within a prosthetic socket is a common
      complaint of many amputees. The heat dissipation in prosthetic sockets is greatly
      influenced by the thermal conductive properties of the socket and interface liner
      materials. These materials influence the body's temperature regulation mechanism
      and might be the reason for thermal discomfort in prosthetic sockets. Monitoring
      interface temperature at skin level is notoriously complicated. The problem might
      be considered notorious because embedding wires and sensors in an elastomer
      eventually results in elastomer failures because of the high strain induced when
      donning a liner (amputees roll the liners onto their limbs). Another reason is
      because placing sensors and wires directly against the skin could cause
      irritation and chaffing over just a short period of time. We describe a route
      wherein if the thermal properties of the socket and liner materials are known,
      the in-socket residual limb temperature could be accurately predicted by
      monitoring the temperature between socket and liner rather than skin and liner
      using the Gaussian process technique. 

PMID- 25389249
TI  - A single dose of benzathine penicillin G is as effective as multiple doses of
      benzathine penicillin G for the treatment of HIV-infected persons with early
      syphilis.
AB  - BACKGROUND: Treatment guidelines recommend the use of a single dose of benzathine
      penicillin G (BPG) for treating early syphilis in human immunodeficiency virus
      (HIV)-infected persons. However, data supporting this recommendation are limited.
      We examined the efficacy of single-dose BPG in the US Military HIV Natural
      History Study. METHODS: Subjects were included if they met serologic criteria for
      syphilis (ie, a positive nontreponemal test [NTr] confirmed by treponemal
      testing). Response to treatment was assessed at 13 months and was defined by a
      >=4-fold decline in NTr titer. Multivariate Cox proportional hazard regression
      models were utilized to examine factors associated with treatment response.
      RESULTS: Three hundred fifty subjects (99% male) contributed 478 cases. Three
      hundred ninety-three cases were treated exclusively with BPG (141 with 1 dose of
      BPG). Treatment response was the same among those receiving 1 or >1 dose of BPG
      (92%). In a multivariate analysis, older age (hazard ratio [HR], 0.82 per 10-year
      increase; 95% confidence interval [CI], .73-.93) was associated with delayed
      response to treatment. Higher pretreatment titers (reference NTr titer <1:64; HR,
      1.94 [95% CI, 1.58-2.39]) and CD4 counts (HR, 1.07 for every 100-cell increase
      [95% CI, 1.01-1.12]) were associated with a faster response to treatment.
      Response was not affected by the number of BPG doses received (reference, 1 dose
      of BPG; HR, 1.11 [95% CI, .89-1.4]). CONCLUSIONS: In this cohort, additional BPG
      doses did not affect treatment response. Our data support the current
      recommendations for the use of a single dose of BPG to treat HIV-infected persons
      with early syphilis.

PMID- 25389250
TI  - Editorial commentary: surgical therapy for Staphylococcus aureus prosthetic valve
      endocarditis: proceed with caution (Caveat Emptor).

PMID- 25389251
TI  - Reply to Freyne et al.

PMID- 25389252
TI  - Psychological stress as a trigger for herpes zoster: might the conventional
      wisdom be wrong?
AB  - The causes for zoster remain largely unknown. Psychological stress is one
      commonly considered risk factor. We used self-controlled case series methods to
      look for increases in zoster following death or catastrophic health event
      occurring in a previously healthy spouse. We found no increase, although this
      stressor led to increased mental health visits. 

PMID- 25389253
TI  - Hospital-wide rollout of antimicrobial stewardship: a stepped-wedge randomized
      trial.

PMID- 25389254
TI  - Durability of antibody response against hepatitis B virus in healthcare workers
      vaccinated as adults.
AB  - BACKGROUND: Follow-up studies of recipients of hepatitis B vaccine from endemic
      areas have reported loss of antibody to hepatitis B surface antigen (anti-HBs) in
      a high proportion of persons vaccinated at birth. In contrast, the long-term
      durability of antibody in persons vaccinated as adults in nonendemic areas is not
      well defined. We aimed to assess the durability of anti-HBs among healthcare
      workers (HCWs) vaccinated as adults and response to a booster among those without
      protective levels of antibody. METHODS: Adult HCWs aged 18-60 at the time of
      initial vaccination were recruited. All were tested for hepatitis B surface
      antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and anti-HBs
      level. HCWs with anti-HBs <12 mIU/mL were offered a booster and levels were
      measured 1, 7, and 21 days afterward. RESULTS: Anti-HBs levels were <12 mIU/mL in
      9 of 50 (18%), 13 of 50 (26%), and 14 of 59 (24%) HCWs 10-15, 16-20, and >20
      years postvaccination, respectively, (P = ns). Four HCWs were anti-HBc positive;
      none had HBsAg. By logistic regression, older age at vaccination was the only
      predictor of inadequate anti-HBs level (P = .0005). Thirty-four of 36 subjects
      with inadequate anti-HBs levels received a booster and 32 (94%) developed levels
      >12 mIU/mL within 3 weeks. CONCLUSIONS: Anti-HBs levels decrease after 10-31
      years and fall below a level considered protective in approximately 25% of cases.
      The rapid and robust response to a booster vaccine suggests a long-lasting
      amnestic response. Hepatitis B vaccination provides long-term protection against
      hepatitis B and booster vaccination does not appear to be necessary in HCWs.
      Clinical Trials Registration. NCT01182311.

PMID- 25389258
TI  - Editorial commentary: The optimal dose of penicillin when treating syphilis in
      HIV-infected persons: enough, already?

PMID- 25389259
TI  - Increase in endemic Neisseria meningitidis capsular group W sequence type 11
      complex associated with severe invasive disease in England and Wales.
AB  - BACKGROUND: In England and Wales, the incidence of invasive meningococcal disease
      has been declining for more than a decade, but meningococcal group W (MenW) cases
      have been increasing since 2009. METHODS: Public Health England conducts enhanced
      national surveillance of invasive meningococcal disease in England and Wales.
      Detailed clinical information was obtained for all laboratory-confirmed MenW
      cases diagnosed during 3 epidemiologic years (2010-2011 to 2012-2013), alongside
      whole-genome sequencing analysis of the clinical isolates. RESULTS: The year-on
      year increase in invasive MenW disease across all age groups since 2009-2010 was
      due to rapid endemic expansion of a single clone belonging to the sequence type
      11 complex (cc11). In 2013-2014, MenW was responsible for 15% of all invasive
      meningococcal disease. All but 1 of the recent MenW:cc11 isolates were very
      closely related, consistent with recent clonal expansion. Clinical follow-up of
      all 129 MenW cases diagnosed during 2010-2011 to 2012-2013 revealed that most
      patients were previously healthy (n = 105 [81%]), had not travelled abroad prior
      to illness and the majority presented with septicemia (n = 63 [49%]), meningitis
      (n = 16 [12%]) or both (n = 21 [16%]); however, one-quarter had atypical
      presentations including pneumonia (n = 15 [12%]), septic arthritis (n = 9 [7%]),
      and epiglottitis/supraglottitis (n = 5 [4%]). Forty-eight (37%) required
      intensive care and 15 (12%) died. There was no association between infecting
      strain, clinical disease, or outcome. CONCLUSIONS: The recent increase in
      invasive MenW disease in England and Wales is due to rapid endemic expansion of a
      single clone belonging to cc11 and is associated with severe disease with unusual
      clinical presentations. This increase will require careful monitoring in the
      coming years.

PMID- 25389256
TI  - Differential body composition effects of protease inhibitors recommended for
      initial treatment of HIV infection: a randomized clinical trial.
AB  - BACKGROUND: It is unclear whether metabolic or body composition effects differ
      between protease inhibitor-based regimens recommended for initial treatment of
      human immunodeficiency virus (HIV) infection. METHODS: ATADAR is a phase 4, open
      label, multicenter, randomized clinical trial. Stable antiretroviral-naive HIV
      infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or
      darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily.
      Predefined endpoints were treatment or virological failure, drug discontinuation
      due to adverse effects, and laboratory and body composition changes at 96 weeks.
      RESULTS: At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%)
      darunavir/ritonavir patients remained free of treatment failure (estimated
      difference 8.2%; 95% confidence interval [CI], -.6 to 21.6) and 71 (79%)
      atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of
      virological failure (estimated difference 6.3%; 95% CI, -.5 to 17.6). Seven
      patients discontinued atazanavir/ritonavir and 5 discontinued darunavir/ritonavir
      due to adverse effects. Total and high-density lipoprotein cholesterol similarly
      increased in both arms, but there was a greater increase in triglycerides in the
      atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr;
      95% CI, 726.7 to 4997.7; P = .0090), limb fat (estimated difference 1403.3 gr;
      95% CI, 388.4 to 2418.2; P = .0071), and subcutaneous abdominal adipose tissue
      (estimated difference 28.4 cm(2); 95% CI, 1.9 to 55.0; P = .0362) increased more
      in the atazanavir/ritonavir arm than in darunavir/ritonavir arm. Body fat changes
      in the atazanavir/ritonavir arm were associated with higher insulin resistance.
      CONCLUSIONS: We found no major differences between atazanavir/ritonavir and
      darunavir/ritonavir in efficacy, clinically relevant side effects, or plasma
      cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides
      and more total and subcutaneous fat than darunavir/ritonavir. Also, fat gains
      with atazanavir/ritonavir were associated with insulin resistance. Clinical
      Trials Registration. NCT01274780.

PMID- 25389261
TI  - Time-resolved assembly of a nucleoprotein complex between Shigella flexneri virF
      promoter and its transcriptional repressor H-NS.
AB  - The virF gene of Shigella, responsible for triggering the virulence cascade in
      this pathogenic bacterium, is transcriptionally repressed by the nucleoid
      associated protein H-NS. The primary binding sites of H-NS within the promoter
      region of virF have been detected here by footprinting experiments in the
      presence of H-NS or its monomeric DNA-binding domain (H-NSctd), which displays
      the same specificity as intact H-NS. Of the 14 short DNA fragments identified, 10
      overlap sequences similar to the H-NS binding motif. The 'fast', 'intermediate'
      and 'slow' H-NS binding events leading to the formation of the nucleoprotein
      complex responsible for transcription repression have been determined by time
      resolved hydroxyl radical footprinting experiments in the presence of full-length
      H-NS. We demonstrate that this process is completed in <=1 s and H-NS protections
      occur simultaneously on site I and site II of the virF promoter. Furthermore, all
      'fast' protections have been identified in regions containing predicted H-NS
      binding motifs, in agreement with the hypothesis that H-NS nucleoprotein complex
      assembles from a few nucleation sites containing high-affinity binding sequences.
      Finally, data are presented showing that the 22-bp fragment corresponding to one
      of the HNS binding sites deviates from canonical B-DNA structure at three TpA
      steps.

PMID- 25389262
TI  - Ribosomes in the balance: structural equilibrium ensures translational fidelity
      and proper gene expression.
AB  - At equilibrium, empty ribosomes freely transit between the rotated and un-rotated
      states. In the cell, the binding of two translation elongation factors to the
      same general region of the ribosome stabilizes one state over the other. These
      stabilized states are resolved by expenditure of energy in the form of GTP
      hydrolysis. A prior study employing mutants of a late assembling peripheral
      ribosomal protein suggested that ribosome rotational status determines its
      affinity for elongation factors, and hence translational fidelity and gene
      expression. Here, mutants of the early assembling integral ribosomal protein uL2
      are used to test the generality of this hypothesis. rRNA structure probing
      analyses reveal that mutations in the uL2 B7b bridge region shift the equilibrium
      toward the rotated state, propagating rRNA structural changes to all of the
      functional centers of ribosome. Structural disequilibrium unbalances ribosome
      biochemically: rotated ribosomes favor binding of the eEF2 translocase and
      disfavor that of the elongation ternary complex. This manifests as specific
      translational fidelity defects, impacting the expression of genes involved in
      telomere maintenance. A model is presented describing how cyclic intersubunit
      rotation ensures the unidirectionality of translational elongation, and how
      perturbation of rotational equilibrium affects specific aspects of translational
      fidelity and cellular gene expression.

PMID- 25389263
TI  - Massively parallel determination and modeling of endonuclease substrate
      specificity.
AB  - We describe the identification and characterization of novel homing endonucleases
      using genome database mining to identify putative target sites, followed by high
      throughput activity screening in a bacterial selection system. We characterized
      the substrate specificity and kinetics of these endonucleases by monitoring DNA
      cleavage events with deep sequencing. The endonuclease specificities revealed by
      these experiments can be partially recapitulated using 3D structure-based
      computational models. Analysis of these models together with genome sequence data
      provide insights into how alternative endonuclease specificities were generated
      during natural evolution. 

PMID- 25389255
TI  - Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic
      valve infective endocarditis: analysis in the International Collaboration of
      Endocarditis-Prospective Cohort Study.
AB  - BACKGROUND: The impact of early valve surgery (EVS) on the outcome of
      Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is
      unresolved. The objective of this study was to evaluate the association between
      EVS, performed within the first 60 days of hospitalization, and outcome of SA
      PVIE within the International Collaboration on Endocarditis-Prospective Cohort
      Study. METHODS: Participants were enrolled between June 2000 and December 2006.
      Cox proportional hazards modeling that included surgery as a time-dependent
      covariate and propensity adjustment for likelihood to receive cardiac surgery was
      used to evaluate the impact of EVS and 1-year all-cause mortality on patients
      with definite left-sided S. aureus PVIE and no history of injection drug use.
      RESULTS: EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality
      was significantly higher among patients with S. aureus PVIE than in patients with
      non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE
      patients who underwent EVS had a significantly lower 1-year mortality rate (33.8%
      vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not
      associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39
      1.15]; P = .15). CONCLUSIONS: In this prospective, multinational cohort of
      patients with S. aureus PVIE, EVS was not associated with reduced 1-year
      mortality. The decision to pursue EVS should be individualized for each patient,
      based upon infection-specific characteristics rather than solely upon the
      microbiology of the infection causing PVIE.

PMID- 25389264
TI  - Oxidative DNA damage is instrumental in hyperreplication stress-induced
      inviability of Escherichia coli.
AB  - In Escherichia coli, an increase in the ATP bound form of the DnaA initiator
      protein results in hyperinitiation and inviability. Here, we show that such
      replication stress is tolerated during anaerobic growth. In hyperinitiating
      cells, a shift from anaerobic to aerobic growth resulted in appearance of
      fragmented chromosomes and a decrease in terminus concentration, leading to a
      dramatic increase in ori/ter ratio and cessation of cell growth. Aerobic
      viability was restored by reducing the level of reactive oxygen species (ROS) or
      by deleting mutM (Fpg glycosylase). The double-strand breaks observed in
      hyperinitiating cells therefore results from replication forks encountering
      single-stranded DNA lesions generated while removing oxidized bases, primarily 8
      oxoG, from the DNA. We conclude that there is a delicate balance between
      chromosome replication and ROS inflicted DNA damage so the number of replication
      forks can only increase when ROS formation is reduced or when the pertinent
      repair is compromised.

PMID- 25389265
TI  - Synergistic modulation of cyclobutane pyrimidine dimer photoproduct formation and
      deamination at a TmCG site over a full helical DNA turn in a nucleosome core
      particle.
AB  - Sunlight-induced C to T mutation hotspots in skin cancers occur primarily at
      methylated CpG sites that coincide with sites of UV-induced cyclobutane
      pyrimidine dimer (CPD) formation. The C or 5-methyl-C in CPDs are not stable and
      deaminate to U and T, respectively, which leads to the insertion of A by DNA
      polymerase eta and defines a probable mechanism for the origin of UV-induced C to
      T mutations. We have now determined the photoproduct formation and deamination
      rates for 10 consecutive T=(m)CG CPDs over a full helical turn at the dyad axis
      of a nucleosome and find that whereas photoproduct formation and deamination is
      greatly inhibited for the CPDs closest to the histone surface, it is greatly
      enhanced for the outermost CPDs. Replacing the G in a T=(m)CG CPD with A greatly
      decreased the deamination rate. These results show that rotational position and
      flanking sequence in a nucleosome can significantly and synergistically modulate
      CPD formation and deamination that contribute to C to T mutations associated with
      skin cancer induction and may have influenced the evolution of the human genome.

PMID- 25389266
TI  - Transcription bypass of DNA lesions enhances cell survival but attenuates
      transcription coupled DNA repair.
AB  - Transcription-coupled DNA repair (TCR) is a subpathway of nucleotide excision
      repair (NER) dedicated to rapid removal of DNA lesions in the transcribed strand
      of actively transcribed genes. The precise nature of the TCR signal and how the
      repair machinery gains access to lesions imbedded in stalled RNA polymerase II
      (RNAP II) complexes in eukaryotic cells are still enigmatic. RNAP II has an
      intrinsic capacity for transcription bypass of DNA lesions by incorporation or
      misincorporation of nucleotides across the lesions. It has been suggested that
      transcription bypass of lesions, which exposes the lesions, may be required for
      TCR. Here, we show that E1103G mutation of Rpb1, the largest subunit of RNAP II,
      which promotes transcription bypass of UV-induced cyclobutane pyrimidine dimers
      (CPDs), increases survival of UV irradiated yeast cells but attenuates TCR. The
      increased cell survival is independent of any NER subpathways. In contrast, G730D
      mutation of Rpb1, which impairs transcription bypass of CPDs, enhances TCR. Our
      results suggest that transcription bypass of lesions attenuates TCR but enhances
      cell tolerance to DNA lesions. Efficient stalling of RNAP II is essential for
      efficient TCR.

PMID- 25389267
TI  - Crystal structure of a DNA/Ba2+ G-quadruplex containing a water-mediated C
      tetrad.
AB  - We have determined the 1.50 A crystal structure of the DNA decamer,
      d(CCA(CNV)KGCGTGG) ((CNV)K, 3-cyanovinylcarbazole), which forms a G-quadruplex
      structure in the presence of Ba(2+). The structure contains several unique
      features including a bulged nucleotide and the first crystal structure
      observation of a C-tetrad. The structure reveals that water molecules mediate
      contacts between the divalent cations and the C-tetrad, allowing Ba(2+) ions to
      occupy adjacent steps in the central ion channel. One ordered Mg(2+) facilitates
      3'-3' stacking of two quadruplexes in the asymmetric unit, while the bulged
      nucleotide mediates crystal contacts. Despite the high diffraction limit, the
      first four nucleotides including the (CNV)K nucleoside are disordered though they
      are still involved in crystal packing. This work suggests that the bulky
      hydrophobic groups may locally influence the formation of non-Watson-Crick
      structures from otherwise complementary sequences. These observations lead to the
      intriguing possibility that certain types of DNA damage may act as modulators of
      G-quadruplex formation.

PMID- 25389268
TI  - A perfect palindrome in the Escherichia coli chromosome forms DNA hairpins on
      both leading- and lagging-strands.
AB  - DNA palindromes are hotspots for DNA double strand breaks, inverted duplications
      and intra-chromosomal translocations in a wide spectrum of organisms from
      bacteria to humans. These reactions are mediated by DNA secondary structures such
      as hairpins and cruciforms. In order to further investigate the pathways of
      formation and cleavage of these structures, we have compared the processing of a
      460 base pair (bp) perfect palindrome in the Escherichia coli chromosome with the
      same construct interrupted by a 20 bp spacer to form a 480 bp interrupted
      palindrome. We show here that the perfect palindrome can form hairpin DNA
      structures on the templates of the leading- and lagging-strands in a replication
      dependent reaction. In the presence of the hairpin endonuclease SbcCD, both
      copies of the replicated chromosome containing the perfect palindrome are
      cleaved, resulting in the formation of an unrepairable DNA double-strand break
      and cell death. This contrasts with the interrupted palindrome, which forms a
      hairpin on the lagging-strand template that is processed to form breaks, which
      can be repaired by homologous recombination.

PMID- 25389269
TI  - Binding site discovery from nucleic acid sequences by discriminative learning of
      hidden Markov models.
AB  - We present a discriminative learning method for pattern discovery of binding
      sites in nucleic acid sequences based on hidden Markov models. Sets of positive
      and negative example sequences are mined for sequence motifs whose occurrence
      frequency varies between the sets. The method offers several objective functions,
      but we concentrate on mutual information of condition and motif occurrence. We
      perform a systematic comparison of our method and numerous published motif
      finding tools. Our method achieves the highest motif discovery performance, while
      being faster than most published methods. We present case studies of data from
      various technologies, including ChIP-Seq, RIP-Chip and PAR-CLIP, of embryonic
      stem cell transcription factors and of RNA-binding proteins, demonstrating
      practicality and utility of the method. For the alternative splicing factor
      RBM10, our analysis finds motifs known to be splicing-relevant. The motif
      discovery method is implemented in the free software package Discrover. It is
      applicable to genome- and transcriptome-scale data, makes use of available repeat
      experiments and aside from binary contrasts also more complex data configurations
      can be utilized.

PMID- 25389270
TI  - Molecular recognition of RhlB and RNase D in the Caulobacter crescentus RNA
      degradosome.
AB  - The endoribonuclease RNase E is a key enzyme in RNA metabolism for many bacterial
      species. In Escherichia coli, RNase E contributes to the majority of RNA turnover
      and processing events, and the enzyme has been extensively characterized as the
      central component of the RNA degradosome assembly. A similar RNA degradosome
      assembly has been described in the alpha-proteobacterium Caulobacter crescentus,
      with the interacting partners of RNase E identified as the Kreb's cycle enzyme
      aconitase, a DEAD-box RNA helicase RhlB and the exoribonuclease polynucleotide
      phosphorylase. Here we report that an additional degradosome component is the
      essential exoribonuclease RNase D, and its recognition site within RNase E is
      identified. We show that, unlike its E. coli counterpart, C. crescentus RhlB
      interacts directly with a segment of the N-terminal catalytic domain of RNase E.
      The crystal structure of a portion of C. crescentus RNase E encompassing the
      helicase-binding region is reported. This structure reveals that an inserted
      segment in the S1 domain adopts an alpha-helical conformation, despite being
      predicted to be natively unstructured. We discuss the implications of these
      findings for the organization and mechanisms of the RNA degradosome.

PMID- 25389271
TI  - Structural insights into the function of a unique tandem GTPase EngA in bacterial
      ribosome assembly.
AB  - Many ribosome-interacting GTPases, with proposed functions in ribosome
      biogenesis, are also implicated in the cellular regulatory coupling between
      ribosome assembly process and various growth control pathways. EngA is an
      essential GTPase in bacteria, and intriguingly, it contains two consecutive
      GTPase domains (GD), being one-of-a-kind among all known GTPases. EngA is
      required for the 50S subunit maturation. However, its molecular role remains
      elusive. Here, we present the structure of EngA bound to the 50S subunit. Our
      data show that EngA binds to the peptidyl transferase center (PTC) and induces
      dramatic conformational changes on the 50S subunit, which virtually returns the
      50S subunit to a state similar to that of the late-stage 50S assembly
      intermediates. Very interestingly, our data show that the two GDs exhibit a
      pseudo-two-fold symmetry in the 50S-bound conformation. Our results indicate that
      EngA recognizes certain forms of the 50S assembly intermediates, and likely
      facilitates the conformational maturation of the PTC of the 23S rRNA in a direct
      manner. Furthermore, in a broad context, our data also suggest that EngA might be
      a sensor of the cellular GTP/GDP ratio, endowed with multiple conformational
      states, in response to fluctuations in cellular nucleotide pool, to facilitate
      and regulate ribosome assembly.

PMID- 25389272
TI  - Double-stranded DNA-dependent ATPase Irc3p is directly involved in mitochondrial
      genome maintenance.
AB  - Nucleic acid-dependent ATPases are involved in nearly all aspects of DNA and RNA
      metabolism. Previous studies have described a number of mitochondrial helicases.
      However, double-stranded DNA-dependent ATPases, including translocases or enzymes
      remodeling DNA-protein complexes, have not been identified in mitochondria of the
      yeast Saccharomyces cerevisae. Here, we demonstrate that Irc3p is a mitochondrial
      double-stranded DNA-dependent ATPase of the Superfamily II. In contrast to the
      other mitochondrial Superfamily II enzymes Mss116p, Suv3p and Mrh4p, which are
      RNA helicases, Irc3p has a direct role in mitochondrial DNA (mtDNA) maintenance.
      Specific Irc3p-dependent mtDNA metabolic intermediates can be detected, including
      high levels of double-stranded DNA breaks that accumulate in irc3Delta mutants.
      irc3Delta-related topology changes in rho- mtDNA can be reversed by the deletion
      of mitochondrial RNA polymerase RPO41, suggesting that Irc3p counterbalances
      adverse effects of transcription on mitochondrial genome stability.

PMID- 25389273
TI  - Modes of TAL effector-mediated repression.
AB  - Engineered transcription activator-like effectors, or TALEs, have emerged as a
      new class of designer DNA-binding proteins. Their DNA recognition sites can be
      specified with great flexibility. When fused to appropriate transcriptional
      regulatory domains, they can serve as designer transcription factors, modulating
      the activity of targeted promoters. We created tet operator (tetO)-specific TALEs
      (tetTALEs), with an identical DNA-binding site as the Tet repressor (TetR) and
      the TetR-based transcription factors that are extensively used in eukaryotic
      transcriptional control systems. Different constellations of tetTALEs and tetO
      modified chromosomal transcription units were analyzed for their efficacy in
      mammalian cells. We find that tetTALE-silencers can entirely abrogate expression
      from the strong human EF1alpha promoter when binding upstream of the
      transcriptional control sequence. Remarkably, the DNA-binding domain of tetTALE
      alone can effectively counteract trans-activation mediated by the potent tettrans
      activator and also directly interfere with RNA polymerase II transcription
      initiation from the strong CMV promoter. Our results demonstrate that TALEs can
      act as highly versatile tools in genetic engineering, serving as trans
      activators, trans-silencers and also competitive repressors.

PMID- 25389274
TI  - Solution structure of the YTH domain in complex with N6-methyladenosine RNA: a
      reader of methylated RNA.
AB  - N(6)A methylation is the most abundant RNA modification occurring within
      messenger RNA. Impairment of methylase or demethylase functions are associated
      with severe phenotypes and diseases in several organisms. Beside writer and
      eraser enzymes of this dynamic RNA epigenetic modification, reader proteins that
      recognize this modification are involved in numerous cellular processes. Although
      the precise characterization of these reader proteins remains unknown,
      preliminary data showed that most potential reader proteins contained a conserved
      YT521-B homology (YTH) domain. Here we define the YTH domain of rat YT521-B as a
      N(6)-methylated adenosine reader domain and report its solution structure in
      complex with a N(6)-methylated RNA. The structure reveals a binding preference
      for NGANNN RNA hexamer and a deep hydrophobic cleft for m(6)A recognition. These
      findings establish a molecular function for YTH domains as m(6)A reader domains
      and should guide further studies into the biological functions of YTH-containing
      proteins in m(6)A recognition. 

PMID- 25389276
TI  - Drug development and nonclinical to clinical translational databases: past and
      current efforts.
AB  - The International Consortium for Innovation and Quality (IQ) in Pharmaceutical
      Development is a science-focused organization of pharmaceutical and biotechnology
      companies. The mission of the Preclinical Safety Leadership Group (DruSafe) of
      the IQ is to advance science-based standards for nonclinical development of
      pharmaceutical products and to promote high-quality and effective nonclinical
      safety testing that can enable human risk assessment. DruSafe is creating an
      industry-wide database to determine the accuracy with which the interpretation of
      nonclinical safety assessments in animal models correctly predicts human risk in
      the early clinical development of biopharmaceuticals. This initiative aligns with
      the 2011 Food and Drug Administration strategic plan to advance regulatory
      science and modernize toxicology to enhance product safety. Although similar in
      concept to the initial industry-wide concordance data set conducted by
      International Life Sciences Institute's Health and Environmental Sciences
      Institute (HESI/ILSI), the DruSafe database will proactively track concordance,
      include exposure data and large and small molecules, and will continue to expand
      with longer duration nonclinical and clinical study comparisons. The output from
      this work will help identify actual human and animal adverse event data to define
      both the reliability and the potential limitations of nonclinical data and
      testing paradigms in predicting human safety in phase 1 clinical trials. 

PMID- 25389275
TI  - A longitudinal cohort study of body mass index and childhood exposure to
      secondhand tobacco smoke and air pollution: the Southern California Children's
      Health Study.
AB  - BACKGROUND: Childhood body mass index (BMI) and obesity prevalence have been
      associated with exposure to secondhand smoke (SHS), maternal smoking during
      pregnancy, and vehicular air pollution. There has been little previous study of
      joint BMI effects of air pollution and tobacco smoke exposure. METHODS:
      Information on exposure to SHS and maternal smoking during pregnancy was
      collected on 3,318 participants at enrollment into the Southern California
      Children's Health Study. At study entry at average age of 10 years, residential
      near-roadway pollution exposure (NRP) was estimated based on a line source
      dispersion model accounting for traffic volume, proximity, and meteorology.
      Lifetime exposure to tobacco smoke was assessed by parent questionnaire.
      Associations with subsequent BMI growth trajectory based on annual measurements
      and attained BMI at 18 years of age were assessed using a multilevel modeling
      strategy. RESULTS: Maternal smoking during pregnancy was associated with
      estimated BMI growth over 8-year follow-up (0.72 kg/m2 higher; 95% CI: 0.14,
      1.31) and attained BMI (1.14 kg/m2 higher; 95% CI: 0.66, 1.62). SHS exposure
      before enrollment was positively associated with BMI growth (0.81 kg/m2 higher;
      95% CI: 0.36, 1.27) and attained BMI (1.23 kg/m2 higher; 95% CI: 0.86, 1.61).
      Growth and attained BMI increased with more smokers in the home. Compared with
      children without a history of SHS and NRP below the median, attained BMI was 0.80
      kg/m2 higher (95% CI: 0.27, 1.32) with exposure to high NRP without SHS; 0.85
      kg/m2 higher (95% CI: 0.43, 1.28) with low NRP and a history of SHS; and 2.15
      kg/m2 higher (95% CI: 1.52, 2.77) with high NRP and a history of SHS (interaction
      p-value 0.007). These results suggest a synergistic effect. CONCLUSIONS: Our
      findings strengthen emerging evidence that exposure to tobacco smoke and NRP
      contribute to development of childhood obesity and suggest that combined
      exposures may have synergistic effects.

PMID- 25389277
TI  - Dermal toxicity studies: factors impacting study interpretation and outcome.
AB  - The field of dermal toxicity continues to evolve in order to accurately predict
      dermal (and systemic) responses in humans to topically applied chemicals.
      Although the testing methods have undergone extensive refinements, idiosyncrasies
      and unexpected issues during the conduct of these studies are not unusual due to
      the plethora of new vehicles available for formulating test substances, changing
      regulatory requirements, and introducting new strain and/or species of laboratory
      animals as no single species or method seems to suffice for evaluating skin
      toxicity. The objective of this article is to illustrate some pragmatic issues
      that should be considered during the conduct as well as interpretation of dermal
      toxicity studies. Routine procedure-related issues such as hair clipping, tape
      stripping, and wrapping the animal's torso to prevent oral ingestion can
      influence the interpretation. Excipients used in dermal toxicity studies may be
      nontoxic when used alone but complex dermal formulations can result in unexpected
      irritation and toxicity. In conclusion, interpretation and risk assessment of
      dermal toxicity studies should be done in a comprehensive manner, taking into
      account procedure-related impact on study results, unique species susceptibility,
      limitation of gross visual (naked eye) observation for evidence of toxicity, and
      normal anatomical variation. 

PMID- 25389278
TI  - Social Information Processing Mechanisms and Victimization: A Literature Review.
AB  - The aim of the current literature review, which is based on 64 empirical studies,
      was to assess to what extent mechanisms of the Social Information Processing
      (SIP) model of Crick and Dodge (1994) are related to victimization. The reviewed
      studies have provided support for the relation between victimization and several
      social information processing mechanisms, especially the interpretation of cues
      and self-efficacy (as part of the response decision). The relationship between
      victimization and other mechanisms, such as the response generation, was only
      studied in a few articles. Until now research has often focused on just one step
      of the model, instead of attempting to measure the associations between multiple
      mechanisms and victimization in multivariate analyses. Such analyses would be
      interesting to gain more insight into the SIP model and its relationship with
      victimization. The few available longitudinal studies show that mechanisms both
      predict victimization (internal locus of control, negative self-evaluations and
      less assertive response selection) and are predicted by victimization (hostile
      attribution of intent and negative evaluations of others). Associations between
      victimization and SIP mechanisms vary across different types and severity of
      victimization (stronger in personal and severe victimization), and different
      populations (stronger among young victims). Practice could focus on these
      stronger associations and the interpretation of cues. More research is needed
      however, to investigate whether intervention programs that address SIP mechanisms
      are suitable for victimization and all relevant populations. 

PMID- 25389279
TI  - Resilience in Survivors of Child Sexual Abuse: A Systematic Review of the
      Literature.
AB  - OBJECTIVE: This review article summarizes empirical research on resilience in
      survivors of child sexual abuse (CSA) and discusses protective factors that are
      associated with adaptive functioning in spite of sexual victimization. METHODS: A
      literature search to identify studies published up to November 2013 was performed
      within the databases PsycINFO, MEDLINE/PubMed, Web of Science, and PSYNDEXplus.
      Additional relevant studies were retrieved using a snowball technique. A total of
      37 articles met the inclusion criteria and were included in the final sample.
      RESULTS: In the studies included in this review, the percentage of CSA survivors
      who were found to have a normal level of functioning despite a history of sexual
      abuse ranged from 10% to 53%. The protective factors that had the best empirical
      support were found to be education, interpersonal and emotional competence,
      control beliefs, active coping, optimism, social attachment, external attribution
      of blame, and most importantly, support from the family and the wider social
      environment. CONCLUSIONS: Preventive and clinical interventions for survivors of
      CSA should utilize psychoeducation and cognitive strategies that are adapted to
      the developmental level of the victim and that seek to enhance social support
      from significant others. Future research should focus on longitudinal research
      designs considering resilience rather as a dynamic process with multiple
      dimensions in a social and developmental context.

PMID- 25389280
TI  - Carotid endarterectomy may be required in addition to best medical treatment for
      some patient subgroups with asymptomatic carotid stenosis.
AB  - Several guidelines recommend carotid endarterectomy for patients with severe
      asymptomatic carotid stenosis to reduce the risk of a future cerebrovascular
      event, as long as the perioperative stroke/death rate is <3%. Based on
      improvements in best medical treatment, it was argued that currently best medical
      treatment alone should comprise the treatment-of-choice for asymptomatic carotid
      stenosis patients and that no intervention is warranted in these individuals.
      While it is true that best medical treatment should be used for the management of
      all asymptomatic carotid stenosis patients, emerging evidence suggests that best
      medical treatment alone may not prevent disease progression and the development
      of symptoms in some asymptomatic carotid stenosis patient subgroups. This article
      analyzes the results of two recent independent studies demonstrating that medical
      therapy alone may not be adequate for stroke prevention in some asymptomatic
      carotid stenosis patient subgroups. These results suggest that besides best
      medical treatment, additional carotid endarterectomy should be considered for
      specific asymptomatic carotid stenosis patients. 

PMID- 25389281
TI  - Reducing door-to-puncture times for intra-arterial stroke therapy: a pilot
      quality improvement project.
AB  - BACKGROUND: Delays to intra-arterial therapy (IAT) lead to worse outcomes in
      stroke patients with proximal occlusions. Little is known regarding the magnitude
      of, and reasons for, these delays. In a pilot quality improvement (QI) project,
      we sought to examine and improve our door-puncture times. METHODS AND RESULTS:
      For anterior-circulation stroke patients who underwent IAT, we retrospectively
      calculated in-hospital time delays associated with various phases from patient
      arrival to groin puncture. We formulated and then implemented a process change
      targeted to the phase with the greatest delay. We examined the impact on time to
      treatment by comparing the pre- and post-QI cohorts. One hundred forty-six
      patients (93 pre- vs. 51 post-QI) were analyzed. In the pre-QI cohort (ie,
      sequential process), the greatest delay occurred from imaging to the
      neurointerventional (NI) suite ("picture-suite": median, 62 minutes;
      interquartile range [IQR], 40 to 82). A QI measure was instituted so that the NI
      team and anesthesiologist were assembled and the suite set up in parallel with
      completion of imaging and decision making. The post-QI (ie, parallel process)
      median picture-to-suite time was 29 minutes (IQR, 21 to 41; P<0.0001). There was
      a 36-minute reduction in median door-to-puncture time (143 vs. 107 minutes;
      P<0.0001). Parallel workflow and presentation during work hours were independent
      predictors of shorter door-puncture times. CONCLUSIONS: In-hospital delays are a
      major obstacle to timely IAT. A simple approach for achieving substantial time
      savings is to mobilize the NI and anesthesia teams during patient evaluation and
      treatment decision making. This parallel workflow resulted in a >30-minute (25%)
      reduction in median door-to-puncture times.

PMID- 25389282
TI  - Synergistic effect of gestational hypertension and postpartum incident
      hypertension on cardiovascular health: a nationwide population study.
AB  - BACKGROUND: Gestational hypertension (GH) is a common complication of pregnancy
      and is associated with increased risk of incident hypertension in later life (IH)
      and cardiovascular events. However, the interactive effect of GH and IH on
      postpartum cardiovascular health remains unclear. METHODS AND RESULTS: A
      nationwide population-based study was conducted using 1 million individuals from
      the Taiwan National Health Insurance database. Records from 1998 to 2009 were
      used to identify 1260 pregnant women with GH and without previous cardiovascular
      disease. The control group comprised 5040 pregnant women without GH, matched for
      age and date of delivery. During the follow-up period (median duration, 5.8
      years), 182 cardiovascular events developed. Women with GH had significantly
      higher risk of cardiovascular events (hazard ratio [95% CI], 2.44 [1.80 to 3.31])
      and IH (8.29 [6.30 to 10.91]) than controls. Compared with women without GH and
      IH, there was a significantly higher risk of cardiovascular events for women
      without GH but with IH (relative risk [95% CI], 2.89 [1.27-6.58]), women with GH
      but without IH (1.66 [1.16-2.39]), and women with GH and IH (8.11 [5.36-12.30]).
      The synergy index was 2.91 (95% CI 1.11 to 7.59), suggesting a positive
      interaction between GH and IH. CONCLUSIONS: GH increased the risk of subsequent
      IH. Women with both GH and IH were at a substantially higher cardiovascular risk
      than were women with either GH or IH. The synergistic adverse effect of GH and IH
      on postpartum cardiovascular health indicates that more attention should be paid
      to this special population.

PMID- 25389283
TI  - Early discharge after primary percutaneous coronary intervention: the added value
      of N-terminal pro-brain natriuretic peptide to the Zwolle Risk Score.
AB  - BACKGROUND: The Zwolle Risk Score (ZRS) identifies ST-elevation myocardial
      infarction (STEMI) patients treated with primary percutaneous coronary
      intervention (PPCI) eligible for early discharge. We aimed to investigate whether
      baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) is also able to
      identify these patients and could improve future risk strategies. METHODS AND
      RESULTS: PPCI patients included in the Ongoing Tirofiban in Myocardial Infarction
      Evaluation (On-TIME) II study were candidates (N=861). We analyzed whether ZRS
      and baseline NT-proBNP predicted 30-day mortality and assessed the occurrence of
      major adverse cardiac events (MACEs) and major bleeding. Receiver operating
      characteristic curve analysis was used to assess discriminative accuracy for ZRS,
      NT-pro-BNP, and their combination. After multiple imputation, 845 patients were
      included. Both ZRS >3 (hazard ratio [HR]=9.42; P<0.001) and log NT-pro-BNP
      (HR=2.61; P<0.001) values were associated with 30-day mortality. On multivariate
      analysis, both the ZRS (HR=1.41; 95% confidence interval [CI]=1.27 to 1.56;
      P<0.001) and log NT-proBNP (HR=2.09; 95% CI=1.59 to 2.74; P<0.001) independently
      predicted death at 30 days. The area under the curve for 30-day mortality for
      combined ZRS/NT-proBNP was 0.94 (95% CI=0.90 to 0.99), with optimal predictive
      values of a ZRS >=2 and a NT-proBNP value of >=200 pg/mL. Using these cut-off
      values, 64% of the study population could be identified as very low risk with
      zero mortality at 30 days follow-up and low occurrence of MACEs and major
      bleeding between 48 hours and 10 days (1.3% and 0.6%, respectively). CONCLUSION:
      Baseline NT-proBNP identifies a large group of low-risk patients who may be
      eligible for early (48- to 72-hour) discharge, whereas optimal predictive
      accuracy is reached by the combination of both baseline NT-proBNP and ZRS.

PMID- 25389284
TI  - Cost-effectiveness of supervised exercise, stenting, and optimal medical care for
      claudication: results from the Claudication: Exercise Versus Endoluminal
      Revascularization (CLEVER) trial.
AB  - BACKGROUND: Both supervised exercise (SE) and stenting (ST) improve functional
      status, symptoms, and quality of life compared with optimal medical care (OMC) in
      patients with claudication. The relative cost-effectiveness of these strategies
      is not well defined. METHODS AND RESULTS: The Claudication: Exercise Versus
      Endoluminal Revascularization (CLEVER) study randomized patients with
      claudication due to aortoiliac stenosis to a 6-month SE program, to ST, or to
      OMC. Participants who completed 6-month follow-up (n=98) were included in a
      health economic analysis through 18 months. Costs were assessed using resource
      based methods and hospital billing data. Quality-adjusted life-years were
      estimated using the EQ-5D. Markov modeling based on the in-trial results was used
      to explore the impact of assumptions about the longer term durability of observed
      differences in quality of life. Through 18 months, mean healthcare costs were
      $5178, $9804, and $14 590 per patient for OMC, SE, and ST, respectively. Measured
      quality-adjusted life-years through 18 months were 1.04, 1.16, and 1.20. In our
      base case analysis, which assumed that observed differences in quality of life
      would dissipate after 5 years, the incremental cost-effectiveness ratios were $24
      070 per quality-adjusted life-year gained for SE versus OMC, $41 376 for ST
      versus OMC, and $122 600 for ST versus SE. If the treatment effect of ST was
      assumed to be more durable than that of SE, the incremental cost-effectiveness
      ratio for ST versus SE became more favorable. CONCLUSIONS: Both SE and ST are
      economically attractive by US standards relative to OMC for the treatment of
      claudication in patients with aortoiliac disease. ST is more expensive than SE,
      with uncertain incremental benefit. CLINICAL TRIAL REGISTRATION URL:
      www.clinicaltrials.gov, Unique identifier: NCT00132743.

PMID- 25389285
TI  - Endothelin-1 induces myofibrillar disarray and contractile vector variability in
      hypertrophic cardiomyopathy-induced pluripotent stem cell-derived cardiomyocytes.
AB  - BACKGROUND: Despite the accumulating genetic and molecular investigations into
      hypertrophic cardiomyopathy (HCM), it remains unclear how this condition develops
      and worsens pathologically and clinically in terms of the genetic-environmental
      interactions. Establishing a human disease model for HCM would help to elucidate
      these disease mechanisms; however, cardiomyocytes from patients are not easily
      obtained for basic research. Patient-specific induced pluripotent stem cells
      (iPSCs) potentially hold much promise for deciphering the pathogenesis of HCM.
      The purpose of this study is to elucidate the interactions between genetic
      backgrounds and environmental factors involved in the disease progression of HCM.
      METHODS AND RESULTS: We generated iPSCs from 3 patients with HCM and 3 healthy
      control subjects, and cardiomyocytes were differentiated. The HCM pathological
      phenotypes were characterized based on morphological properties and high-speed
      video imaging. The differences between control and HCM iPSC-derived
      cardiomyocytes were mild under baseline conditions in pathological features. To
      identify candidate disease-promoting environmental factors, the cardiomyocytes
      were stimulated by several cardiomyocyte hypertrophy-promoting factors.
      Interestingly, endothelin-1 strongly induced pathological phenotypes such as
      cardiomyocyte hypertrophy and intracellular myofibrillar disarray in the HCM iPSC
      derived cardiomyocytes. We then reproduced these phenotypes in neonatal
      cardiomyocytes from the heterozygous Mybpc3-targeted knock in mice. High-speed
      video imaging with motion vector prediction depicted physiological contractile
      dynamics in the iPSC-derived cardiomyocytes, which revealed that self-beating HCM
      iPSC-derived single cardiomyocytes stimulated by endothelin-1 showed variable
      contractile directions. CONCLUSIONS: Interactions between the patient's genetic
      backgrounds and the environmental factor endothelin-1 promote the HCM
      pathological phenotype and contractile variability in the HCM iPSC-derived
      cardiomyocytes.

PMID- 25389287
TI  - Knockout of nuclear high molecular weight FGF2 isoforms in mice modulates bone
      and phosphate homeostasis.
AB  - We previously reported that targeted overexpression of the fibroblast growth
      factor 2 (FGF2) high molecular weight (HMW) isoforms in osteoblastic lineage
      cells in mice resulted in phenotypic changes, including dwarfism, rickets,
      osteomalacia, hypophosphatemia, increased serum parathyroid hormone, and
      increased levels of the phosphatonin FGF23 in serum and bone. This study examined
      the effects of genetically knocking out the FGF2HMW isoforms (HMWKO) on bone and
      phosphate homeostasis. HMWKO mice were not dwarfed and had significantly
      increased bone mineral density and bone mineral content in femurs and lumbar
      vertebrae when compared with the wild-type (WT) littermates. Micro-computed
      tomography analysis of femurs revealed increased trabecular bone volume,
      thickness, number, and connective tissue density with decreased trabecular
      spacing compared with WT. In addition, there was significantly decreased cortical
      porosity and increased cortical thickness and sub-periosteal area in femurs of
      HMWKO. Histomorphometric analysis demonstrated increased osteoblast activity and
      diminished osteoclast activity in the HMWKO. In vitro bone marrow stromal cell
      cultures showed there was a significant increase in alkaline phosphatase-positive
      colony number at 1 week in HMWKO. At 3 weeks of culture, the mineralized area was
      also significantly increased. There was increased expression of osteoblast
      differentiation marker genes and reduced expression of genes associated with
      impaired mineralization, including a significant reduction in Fgf23 and Sost
      mRNA. Normal serum phosphate and parathyroid hormone were observed in HMWKO mice.
      This study demonstrates a significant negative impact of HMWFGF2 on biological
      functions in bone and phosphate homeostasis in mice. 

PMID- 25389286
TI  - Association of noninvasively measured left ventricular mechanics with in vitro
      muscle contractile performance: a prospective study in hypertrophic
      cardiomyopathy patients.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary myopathic process in
      which regional left ventricular dysfunction may exist without overt global left
      ventricular dysfunction. In obstructive HCM patients who underwent surgical
      myectomy (SM), we sought to determine if there is a significant association
      between echocardiographic longitudinal strain, histopathology, and in vitro
      myocardial performance (resting tension and developed tension) of the surgical
      specimen. METHODS AND RESULTS: HCM patients (n=122, 54+/-14 years, 54% men)
      undergoing SM were prospectively recruited. Longitudinal systolic strain and
      diastolic strain rates were measured at that basal septum (partially removed at
      SM) by using velocity vector imaging on preoperative echocardiography.
      Semiquantitative histopathologic grading of myocyte disarray and fibrosis and in
      vitro measurements of resting tension and developed tension were made in septal
      tissue obtained at SM. Mean basal septal systolic strain and diastolic strain
      rate were -8.3+/-5% and 0.62+/-0.4/s, while mild or greater degree of myocyte
      disarray and interstitial fibrosis were present in 85% and 87%, respectively.
      Mean resting tension and developed tension were 2.8+/-1 and 1.4+/-0.8 g/mm(2). On
      regression analysis, basal septal systolic strain, diastolic strain rate,
      disarray, and fibrosis were associated with developed tension (beta=0.19, 0.20, 
      0.33, and -0.40, respectively, all P<0.01) and resting tension (beta=0.21, 0.22, 
      0.25, and -0.28, respectively, all P<0.01). CONCLUSION: In obstructive HCM
      patients who underwent SM, left ventricular mechanics (echocardiographic
      longitudinal systolic strain and diastolic strain rates), assessed at the basal
      septum (myocardium removed during myectomy) and histopathologic findings
      characteristic for HCM (disarray and fibrosis) were significantly associated with
      in vitro myocardial resting and developed contractile performance.

PMID- 25389288
TI  - Autolytic activation of calpain 3 proteinase is facilitated by calmodulin
      protein.
AB  - Calpains are broadly distributed, calcium-dependent enzymes that induce limited
      proteolysis in a wide range of substrates. Mutations in the gene encoding the
      muscle-specific family member calpain 3 (CAPN3) underlie limb-girdle muscular
      dystrophy 2A. We have shown previously that CAPN3 knockout muscles exhibit
      attenuated calcium release, reduced calmodulin kinase (CaMKII) signaling, and
      impaired muscle adaptation to exercise. However, neither the precise role of
      CAPN3 in these processes nor the mechanisms of CAPN3 activation in vivo have been
      fully elucidated. In this study, we identify calmodulin (CaM), a known transducer
      of the calcium signal, as the first positive regulator of CAPN3 autolytic
      activity. CaM was shown to bind CAPN3 at two sites located in the C2L domain.
      Biochemical studies using muscle extracts from transgenic mice overexpressing
      CAPN3 or its inactive mutant revealed that CaM binding enhanced CAPN3 autolytic
      activation. Furthermore, CaM facilitated CAPN3-mediated cleavage of its in vivo
      substrate titin in tissue extracts. Therefore, these studies reveal a novel
      interaction between CAPN3 and CaM and identify CaM as the first positive
      regulator of CAPN3 activity. 

PMID- 25389289
TI  - Histone deacetylase 7 (Hdac7) suppresses chondrocyte proliferation and beta
      catenin activity during endochondral ossification.
AB  - Histone deacetylases (Hdacs) regulate endochondral ossification by suppressing
      gene transcription and modulating cellular responses to growth factors and
      cytokines. We previously showed that Hdac7 suppresses Runx2 activity and
      osteoblast differentiation. In this study, we examined the role of Hdac7 in
      postnatal chondrocytes. Hdac7 was highly expressed in proliferating cells within
      the growth plate. Postnatal tissue-specific ablation of Hdac7 with a tamoxifen
      inducible collagen type 2a1-driven Cre recombinase increased proliferation and
      beta-catenin levels in growth plate chondrocytes and expanded the proliferative
      zone. Similar results were obtained in primary chondrocyte cultures where Hdac7
      was deleted with adenoviral-Cre. Hdac7 bound beta-catenin in proliferating
      chondrocytes, but stimulation of chondrocyte maturation promoted the
      translocation of Hdac7 to the cytoplasm where it was degraded by the proteasome.
      As a result, beta-catenin levels and transcription activity increased in the
      nucleus. These data demonstrate that Hdac7 suppresses proliferation and beta
      catenin activity in chondrocytes. Reducing Hdac7 levels in early chondrocytes may
      promote the expansion and regeneration of cartilage tissues. 

PMID- 25389290
TI  - Miropin, a novel bacterial serpin from the periodontopathogen Tannerella
      forsythia, inhibits a broad range of proteases by using different peptide bonds
      within the reactive center loop.
AB  - All prokaryotic genes encoding putative serpins identified to date are found in
      environmental and commensal microorganisms, and only very few prokaryotic serpins
      have been investigated from a mechanistic standpoint. Herein, we characterized a
      novel serpin (miropin) from the human pathogen Tannerella forsythia, a bacterium
      implicated in initiation and progression of human periodontitis. In contrast to
      other serpins, miropin efficiently inhibited a broad range of proteases
      (neutrophil and pancreatic elastases, cathepsin G, subtilisin, and trypsin) with
      a stoichiometry of inhibition of around 3 and second-order association rate
      constants that ranged from 2.7 * 10(4) (cathepsin G) to 7.1 * 10(5) m(-1)s(-1)
      (subtilisin). Inhibition was associated with the formation of complexes that were
      stable during SDS-PAGE. The unusually broad specificity of miropin for target
      proteases is achieved through different active sites within the reactive center
      loop upstream of the P1-P1' site, which was predicted from an alignment of the
      primary structure of miropin with those of well studied human and prokaryotic
      serpins. Thus, miropin is unique among inhibitory serpins, and it has apparently
      evolved the ability to inhibit a multitude of proteases at the expense of a high
      stoichiometry of inhibition and a low association rate constant. These
      characteristics suggest that miropin arose as an adaptation to the highly
      proteolytic environment of subgingival plaque, which is exposed continually to an
      array of host proteases in the inflammatory exudate. In such an environment,
      miropin may function as an important virulence factor by protecting bacterium
      from the destructive activity of neutrophil serine proteases. Alternatively, it
      may act as a housekeeping protein that regulates the activity of endogenous T.
      forsythia serine proteases. 

PMID- 25389291
TI  - Disassembly of Lys11 and mixed linkage polyubiquitin conjugates provides insights
      into function of proteasomal deubiquitinases Rpn11 and Ubp6.
AB  - Protein homeostasis is largely dependent on proteolysis by the ubiquitin
      proteasome system. Diverse polyubiquitin modifications are reported to target
      cellular proteins to the proteasome. At the proteasome, deubiquitination is an
      essential preprocessing event that contributes to degradation efficiency. We
      characterized the specificities of two proteasome-associated deubiquitinases
      (DUBs), Rpn11 and Ubp6, and explored their impact on overall proteasome DUB
      activity. This was accomplished by constructing a panel of well defined ubiquitin
      (Ub) conjugates, including homogeneous linkages of varying lengths as well as a
      heterogeneously modified target. Rpn11 and Ubp6 processed Lys(11) and Lys(63)
      linkages with comparable efficiencies that increased with chain length. In
      contrast, processing of Lys(48) linkages by proteasome was inversely correlated
      to chain length. Fluorescently labeled tetra-Ub chains revealed endo-chain
      preference for Ubp6 acting on Lys(48) and random action for Rpn11. Proteasomes
      were more efficient at deconjugating identical substrates than their constituent
      DUBs by roughly 2 orders of magnitude. Incorporation into proteasomes
      significantly enhanced enzymatic efficiency of Rpn11, due in part to alleviation
      of the autoinhibitory role of its C terminus. The broad specificity of Rpn11
      could explain how proteasomes were more effective at disassembling a
      heterogeneously modified conjugate compared with homogeneous Lys(48)-linked
      chains. The reduced ability to disassemble homogeneous Lys(48)-linked chains
      longer than 4 Ub units may prolong residency time on the proteasome. 

PMID- 25389292
TI  - Peroxisome proliferator-activated receptor-alpha-mediated transcription of miR
      199a2 attenuates endothelin-1 expression via hypoxia-inducible factor-1alpha.
AB  - Endothelin-1, a potent vasoconstrictor, plays an important role in pulmonary
      hypertension (PH) in sickle cell disease (SCD). Our previous studies show that
      higher levels of placenta growth factor (PlGF), secreted by erythroid precursor
      cells, correlate with increased plasma levels of endothelin-1 (ET-1) and other
      functional markers of PH in SCD. PlGF-mediated ET-1 expression occurs via
      activation of hypoxia-inducible factor-1alpha (HIF-1alpha). However, relatively
      less is understood regarding how PlGF-mediated expression of HIF-1alpha and its
      downstream effector ET-1 are post-transcriptionally regulated. Herein, we show
      that PlGF treatment of endothelial cells resulted in reduced levels of miR-199a2,
      which targeted the 3'-UTR of HIF-1alpha mRNA and concomitantly led to augmented
      ET-1 expression. Plasma levels of miR-199a2 in SCD subjects were significantly
      lower with reciprocally high levels of plasma ET-1, unlike unaffected controls.
      This observation provided a molecular link between miR-199a2 and high levels of
      ET-1 in SCD. Furthermore, we show that miR-199a2 located in the DNM3os
      transcription unit was co-transcriptionally regulated by peroxisome proliferator
      activated receptor alpha (PPARalpha). Binding of the latter to PPARalpha cis
      elements in the promoter of DNM3os was demonstrated by promoter mutational
      analysis and ChIP. Additionally, we show that fenofibrate, a PPARalpha agonist,
      increased the expression of miR-199a2 and DNM3os; the former was responsible for
      reduced expression of HIF-1alpha and ET-1. In vivo studies of fenofibrate-fed
      Berkeley sickle mice resulted in increased levels of miR-199a2 and reduced levels
      of ET-1 in lung tissues. Our studies provide a potential therapeutic approach
      whereby fenofibrate-induced miR-199a2 expression can ameliorate PH by reduction
      of ET-1 levels. 

PMID- 25389293
TI  - Relaxin activates peroxisome proliferator-activated receptor gamma (PPARgamma)
      through a pathway involving PPARgamma coactivator 1alpha (PGC1alpha).
AB  - Relaxin activation of its receptor RXFP1 triggers multiple signaling pathways.
      Previously, we have shown that relaxin activates PPARgamma transcriptional
      activity in a ligand-independent manner, but the mechanism for this effect was
      unknown. In this study, we examined the signaling pathways of downstream of RXFP1
      leading to PPARgamma activation. Using cells stably expressing RXFP1, we found
      that relaxin regulation of PPARgamma activity requires accumulation of cAMP and
      subsequent activation of cAMP-dependent protein kinase (PKA). The activated PKA
      subsequently phosphorylated cAMP response element-binding protein (CREB) at Ser
      133 to activate it directly, as well as indirectly through mitogen activated
      protein kinase p38 MAPK. Activated CREB was required for relaxin stimulation of
      PPARgamma activity, while there was no evidence for a role of the nitric oxide or
      ERK MAPK pathways. Relaxin increased the mRNA and protein levels of the
      coactivator protein PGC1alpha, and this effect was dependent on PKA, and was
      completely abrogated by a dominant-negative form of CREB. This mechanism was
      confirmed in a hepatic stellate cell line stably that endogenously expresses
      RXFP1. Reduction of PGC1alpha levels using siRNA diminished the regulation of
      PPARgamma by relaxin. These results suggest that relaxin activates the cAMP/PKA
      and p38 MAPK pathways to phosphorylate CREB, resulting in increased PGC1alpha
      levels. This provides a mechanism for the ligand-independent activation of
      PPARgamma in response to relaxin. 

PMID- 25389294
TI  - Structural and biochemical insights into the activation mechanisms of germinal
      center kinase OSR1.
AB  - The oxidative stress-responsive 1 (OSR1) kinase belongs to the mammalian STE20
      like kinase family. OSR1 is activated by with no lysine [K] (WNKs) kinases, and
      then it phosphorylates cation-coupled Cl-cotransporters, regulating ion
      homeostasis and cell volume in mammalian cells. However, the specific mechanisms
      of OSR1 activation remains poorly defined, largely due to its extremely low basal
      activity. Here, we dissect in detail the regulatory mechanisms of OSR1 activation
      from the aspects of autoinhibition, upstream kinase WNK, and the newly identified
      master regulator mouse protein-25 (MO25). Based on our structural and biochemical
      studies, we propose a "double lock" model, accounting for the tight
      autoinhibition of OSR1, an effect that has to be removed by WNK before MO25
      further activates OSR1. Particularly, the conserved C-terminal (CCT) domain and
      alphaAL helix act together to strongly suppress OSR1 basal activity. WNKs bind to
      the CCT and trigger its conformational rearrangement to release the kinase domain
      of OSR1, allowing for MO25 binding and full activation. Finally, the regulatory
      mechanisms of OSR1 activation were further corroborated by cellular studies of
      OSR1-regulated cell volume control through WNK-OSR1 signaling pathway.
      Collectively, these results provide insights into the OSR1 kinase activation to
      facilitate further functional study. 

PMID- 25389295
TI  - Na+ inhibits the epithelial Na+ channel by binding to a site in an extracellular
      acidic cleft.
AB  - The epithelial Na(+) channel (ENaC) has a key role in the regulation of
      extracellular fluid volume and blood pressure. ENaC belongs to a family of ion
      channels that sense the external environment. These channels have large
      extracellular regions that are thought to interact with environmental cues, such
      as Na(+), Cl(-), protons, proteases, and shear stress, which modulate gating
      behavior. We sought to determine the molecular mechanism by which ENaC senses
      high external Na(+) concentrations, resulting in an inhibition of channel
      activity. Both our structural model of an ENaC alpha subunit and the resolved
      structure of an acid-sensing ion channel (ASIC1) have conserved acidic pockets in
      the periphery of the extracellular region of the channel. We hypothesized that
      these acidic pockets host inhibitory allosteric Na(+) binding sites. Through site
      directed mutagenesis targeting the acidic pocket, we modified the inhibitory
      response to external Na(+). Mutations at selected sites altered the cation
      inhibitory preference to favor Li(+) or K(+) rather than Na(+). Channel activity
      was reduced in response to restraining movement within this region by cross
      linking structures across the acidic pocket. Our results suggest that residues
      within the acidic pocket form an allosteric effector binding site for Na(+). Our
      study supports the hypothesis that an acidic cleft is a key ligand binding locus
      for ENaC and perhaps other members of the ENaC/degenerin family. 

PMID- 25389296
TI  - Pseudomonas aeruginosa minor pilins prime type IVa pilus assembly and promote
      surface display of the PilY1 adhesin.
AB  - Type IV pili (T4P) contain hundreds of major subunits, but minor subunits are
      also required for assembly and function. Here we show that Pseudomonas aeruginosa
      minor pilins prime pilus assembly and traffic the pilus-associated adhesin and
      anti-retraction protein, PilY1, to the cell surface. PilV, PilW, and PilX require
      PilY1 for inclusion in surface pili and vice versa, suggestive of complex
      formation. PilE requires PilVWXY1 for inclusion, suggesting that it binds a novel
      interface created by two or more components. FimU is incorporated independently
      of the others and is proposed to couple the putative minor pilin-PilY1 complex to
      the major subunit. The production of small amounts of T4P by a mutant lacking the
      minor pilin operon was traced to expression of minor pseudopilins from the P.
      aeruginosa type II secretion (T2S) system, showing that under retraction
      deficient conditions, T2S minor subunits can prime T4P assembly. Deletion of all
      minor subunits abrogated pilus assembly. In a strain lacking the minor
      pseudopilins, PilVWXY1 and either FimU or PilE comprised the minimal set of
      components required for pilus assembly. Supporting functional conservation of T2S
      and T4P minor components, our 1.4 A crystal structure of FimU revealed striking
      architectural similarity to its T2S ortholog GspH, despite minimal sequence
      identity. We propose that PilVWXY1 form a priming complex for assembly and that
      PilE and FimU together stably couple the complex to the major subunit.
      Trafficking of the anti-retraction factor PilY1 to the cell surface allows for
      production of pili of sufficient length to support adherence and motility. 

PMID- 25389298
TI  - Molecular insights into the coding region determinant-binding protein-RNA
      interaction through site-directed mutagenesis in the heterogeneous nuclear
      ribonucleoprotein-K-homology domains.
AB  - The ability of its four heterogeneous nuclear RNP-K-homology (KH) domains to
      physically associate with oncogenic mRNAs is a major criterion for the function
      of the coding region determinant-binding protein (CRD-BP). However, the
      particular RNA-binding role of each of the KH domains remains largely unresolved.
      Here, we mutated the first glycine to an aspartate in the universally conserved
      GXXG motif of the KH domain as an approach to investigate their role. Our results
      show that mutation of a single GXXG motif generally had no effect on binding, but
      the mutation in any two KH domains, with the exception of the combination of KH3
      and KH4 domains, completely abrogated RNA binding in vitro and significantly
      retarded granule formation in zebrafish embryos, suggesting that any combination
      of at least two KH domains cooperate in tandem to bind RNA efficiently.
      Interestingly, we found that any single point mutation in one of the four KH
      domains significantly impacted CRD-BP binding to mRNAs in HeLa cells, suggesting
      that the dynamics of the CRD-BP-mRNA interaction vary over time in vivo.
      Furthermore, our results suggest that different mRNAs bind preferentially to
      distinct CRD-BP KH domains. The novel insights revealed in this study have
      important implications on the understanding of the oncogenic mechanism of CRD-BP
      as well as in the future design of inhibitors against CRD-BP function. 

PMID- 25389297
TI  - Sites of superoxide and hydrogen peroxide production by muscle mitochondria
      assessed ex vivo under conditions mimicking rest and exercise.
AB  - The sites and rates of mitochondrial production of superoxide and H2O2 in vivo
      are not yet defined. At least 10 different mitochondrial sites can generate these
      species. Each site has a different maximum capacity (e.g. the outer quinol site
      in complex III (site IIIQo) has a very high capacity in rat skeletal muscle
      mitochondria, whereas the flavin site in complex I (site IF) has a very low
      capacity). The maximum capacities can greatly exceed the actual rates observed in
      the absence of electron transport chain inhibitors, so maximum capacities are a
      poor guide to actual rates. Here, we use new approaches to measure the rates at
      which different mitochondrial sites produce superoxide/H2O2 using isolated muscle
      mitochondria incubated in media mimicking the cytoplasmic substrate and effector
      mix of skeletal muscle during rest and exercise. We find that four or five sites
      dominate during rest in this ex vivo system. Remarkably, the quinol site in
      complex I (site IQ) and the flavin site in complex II (site IIF) each account for
      about a quarter of the total measured rate of H2O2 production. Site IF, site
      IIIQo, and perhaps site EF in the beta-oxidation pathway account for most of the
      remainder. Under conditions mimicking mild and intense aerobic exercise, total
      production is much less, and the low capacity site IF dominates. These results
      give novel insights into which mitochondrial sites may produce superoxide/H2O2 in
      vivo. 

PMID- 25389299
TI  - Up-regulation of thrombospondin-2 in Akt1-null mice contributes to compromised
      tissue repair due to abnormalities in fibroblast function.
AB  - Vascular remodeling is essential for tissue repair and is regulated by multiple
      factors, including thrombospondin-2 (TSP2) and hypoxia/VEGF-induced activation of
      Akt. In contrast to TSP2 knock-out (KO) mice, Akt1 KO mice have elevated TSP2
      expression and delayed tissue repair. To investigate the contribution of
      increased TSP2 to Akt1 KO mice phenotypes, we generated Akt1/TSP2 double KO (DKO)
      mice. Full-thickness excisional wounds in DKO mice healed at an accelerated rate
      when compared with Akt1 KO mice. Isolated dermal Akt1 KO fibroblasts expressed
      increased TSP2 and displayed altered morphology and defects in migration and
      adhesion. These defects were rescued in DKO fibroblasts or after TSP2 knockdown.
      Conversely, the addition of exogenous TSP2 to WT cells induced cell morphology
      and migration rates that were similar to those of Akt1 KO cells. Akt1 KO
      fibroblasts displayed reduced adhesion to fibronectin with manganese stimulation
      when compared with WT and DKO cells, revealing an Akt1-dependent role for TSP2 in
      regulating integrin-mediated adhesions; however, this effect was not due to
      changes in beta1 integrin surface expression or activation. Consistent with these
      results, Akt1 KO fibroblasts displayed reduced Rac1 activation that was dependent
      upon expression of TSP2 and could be rescued by a constitutively active Rac
      mutant. Our observations show that repression of TSP2 expression is a critical
      aspect of Akt1 function in tissue repair. 

PMID- 25389301
TI  - Perceptions of health system orientation: quality, patient centeredness, and
      cultural competency.
AB  - As part of a pragmatic trial to reduce hypertension disparities, we conducted a
      baseline organizational assessment to identify aspects of organizational
      functioning that could affect the success of our interventions. Through
      qualitative interviewing and the administration of two surveys, we gathered data
      about health care personnel's perceptions of their organization's orientations
      toward quality, patient centeredness, and cultural competency. We found that
      personnel perceived strong orientations toward quality and patient centeredness.
      The prevalence of these attitudes was significantly higher for these areas than
      for cultural competency and varied by occupational role and race. Larger
      percentages of survey respondents perceived barriers to addressing disparities
      than barriers to improving safety and quality. Health care managers and policy
      makers should consider how we have built strong quality orientations and apply
      those lessons to cultural competency. 

PMID- 25389302
TI  - Correspondence--'A study of noninvasive positive-pressure mechanical ventilation
      in the treatment of acute lung injury with a complex critical care ventilator. Is
      it the best choice?'.

PMID- 25389303
TI  - Opinion: Building a 21st-century infrastructure for the social sciences.

PMID- 25389304
TI  - Inner workings: Breaking down bees' dances.

PMID- 25389306
TI  - Plasma cytokine levels and risk of HIV type 1 (HIV-1) transmission and
      acquisition: a nested case-control study among HIV-1-serodiscordant couples.
AB  - BACKGROUND: A heightened proinflammatory state has been hypothesized to enhance
      human immunodeficiency virus type 1 (HIV-1) transmission - both susceptibility of
      HIV-1-exposed persons and infectiousness of HIV-1-infected persons. METHODS:
      Using prospective data from heterosexual African couples with HIV-1
      serodiscordance, we conducted a nested case-control analysis to assess the
      relationship between cytokine concentrations and the risk of HIV-1 acquisition.
      Case couples (n = 120) were initially serodiscordant couples in which HIV-1 was
      transmitted to the seronegative partner during the study; control couples (n =
      321) were serodiscordant couples in which HIV-1 was not transmitted to the
      seronegative partner. Differences in a panel of 30 cytokines were measured using
      plasma specimens from both HIV-1-susceptible and HIV-1-infected partners. Plasma
      was collected before seroconversion for cases. RESULTS: For both HIV-1-infected
      and HIV-1-susceptible partners, cases and controls had significantly different
      mean responses in cytokine panels (P < .001, by the Hotelling T(2) test),
      suggesting a broadly different pattern of immune activation for couples in which
      HIV-1 was transmitted, compared with couples without transmission. Individually,
      log10 mean concentrations of interleukin 10 (IL-10) and CXCL10 were significantly
      higher for both HIV-1-susceptible and HIV-1-infected case partners, compared with
      HIV-1-susceptible and HIV-1-infected control partners (P < .01 for all
      comparisons). In multivariate analysis, HIV-1 transmission was significantly
      associated with elevated CXCL10 concentrations in HIV-1-susceptible partners (P =
      .001) and with elevated IL-10 concentrations in HIV-1-infected partners (P =
      .02). CONCLUSIONS: Immune activation, as measured by levels of cytokine markers,
      particularly elevated levels of IL-10 and CXCL1, are associated with increased
      HIV-1 susceptibility and infectiousness.

PMID- 25389308
TI  - Acute phase protein alpha1-antitrypsin reduces the bacterial burden in mice by
      selective modulation of innate cell responses.
AB  - BACKGROUND: Severe bacterial infection can cause sepsis, multiple organ
      dysfunction syndrome (MODS), and death. Human alpha1-antitrypsin (hAAT) is an
      antiinflammatory, immune-modulating, and tissue-protective circulating serine
      protease inhibitor, with levels that increase during acute-phase responses. It is
      currently being evaluated as a therapeutic agent for individuals with diabetes
      and graft-versus-host disease. However, the concern of opportunistic bacterial
      infections has yet to be addressed. Therefore, we investigated host immune cell
      responses during acute bacterial infections under conditions of elevated hAAT
      levels. METHODS: Peritonitis and sepsis models were created using wild-type mice
      and hAAT-transgenic mice. Bacterial loads, MODS, leukopenia, neutrophil
      infiltration, immune cell activation, circulating cytokine levels, and survival
      rates were then assessed. RESULTS: hAAT significantly reduced infection-induced
      leukopenia and liver, pancreas, and lung injury, and it significantly improved 24
      hour survival rates. Unexpectedly, bacterial load was reduced. Levels of early
      proinflammatory mediators and neutrophil influx were increased by hAAT soon after
      infection but not during sterile peritonitis. CONCLUSIONS: hAAT reduces the
      bacterial burden after infection. Since hAAT does not block bacterial growth in
      culture, its effects might rely on host immune cell modulation. These outcomes
      suggest that prolonged hAAT treatment in patients without hAAT deficiency is
      safe. Additionally, hAAT treatment may be considered a preemptive therapeutic
      measure for individuals who are at risk for bacterial infections.

PMID- 25389307
TI  - Global origin and transmission of hepatitis C virus nonstructural protein 3 Q80K
      polymorphism.
AB  - Hepatitis C virus (HCV) has a naturally occurring polymorphism, Q80K, in the
      nonstructural protein 3 (NS3) gene encoding the viral protease, which has been
      associated with reduced susceptibility to the direct-acting antiviral inhibitor
      simeprevir. Q80K is observed predominantly in HCV genotype 1a and seldom in other
      HCV genotypes; moreover, it has a markedly high prevalence in the United States.
      Here, we reconstruct the evolutionary history of this polymorphism to investigate
      why it is so highly localized in prevalence and whether it is stably transmitted
      between hosts. We found that the majority (96%) of HCV infections carrying Q80K
      were descended from a single lineage in which a Q80K substitution occurred around
      the 1940s in the United States, which implies that this polymorphism is likely
      highly transmissible. Furthermore, we identified 2 other substitutions in NS3
      that may interact with Q80K and contribute to its stability. Our results imply
      that the current distribution and prevalence of Q80K are unlikely to change
      significantly in the short term. 

PMID- 25389300
TI  - Effectiveness of a brief primary care intervention to reduce passive smoking in
      babies: a cluster randomised clinical trial.
AB  - BACKGROUND: Tobacco smoke pollution (TSP) has major negative effects on infant
      health. Our objectives were to determine the effectiveness of a brief primary
      care intervention directed at parents who smoke in reducing babies' TSP exposure,
      and to establish variables related to greater exposure. METHOD: A multicentre,
      open, cluster-randomised clinical trial in Catalonia. The 83 participating
      primary health paediatric teams of the Catalan Health Service recruited 1101
      babies whose parents were smokers. The intervention group (IG) received a brief
      TSP intervention; the control group (CG) received the usual care. Outcomes were
      measured by parents' reported strategies to avoid TSP exposure. Baseline clinical
      data and characteristics of each baby's TSP exposure were collected, along with
      infant hair samples and parents' tobacco use and related attitudes/behaviours. At
      3-month and 6-month follow-up, behavioural changes to avoid TSP exposure were
      recorded; the association between reported parental behaviours and nicotine
      concentration in infant hair samples was tested in a random sample of 253 babies
      at baseline and 6 months. RESULTS: During follow-up, TSP-avoidance strategies
      improved more in the IG than in the CG: 35.4% and 26.9% ( p=0.006) at home, and
      62.2% and 53.1% in cars (p=0.008). Logistic regression showed adjusted ORs for
      appropriate measures in the IG versus CG of 1.59 (95% CI 1.21 to 2.09) at home
      and 1.30 (95% CI 0.97 to 1.75) in cars. Hair samples showed that 78.7% of the
      babies tested were exposed. Reduced nicotine concentration was associated with
      improved implementation of effective strategies reported by parents at home
      (p=0.029) and in cars (p=0.014). CONCLUSIONS: The intervention produced
      behavioural changes to avoid TSP exposure in babies. The proportion of babies
      with nicotine (>=1ng/mg) in hair samples at baseline is a concern. TRIAL
      REGISTRATION NUMBER: Clinical Trials.gov Identifier: NCT00788996.

PMID- 25389309
TI  - Degradation of mouse locomotor pattern in the absence of proprioceptive sensory
      feedback.
AB  - Mammalian locomotor programs are thought to be directed by the actions of spinal
      interneuron circuits collectively referred to as "central pattern generators."
      The contribution of proprioceptive sensory feedback to the coordination of
      locomotor activity remains less clear. We have analyzed changes in mouse
      locomotor pattern under conditions in which proprioceptive feedback is attenuated
      genetically and biomechanically. We find that locomotor pattern degrades upon
      elimination of proprioceptive feedback from muscle spindles and Golgi tendon
      organs. The degradation of locomotor pattern is manifest as the loss of
      interjoint coordination and alternation of flexor and extensor muscles. Group
      Ia/II sensory feedback from muscle spindles has a predominant influence in
      patterning the activity of flexor muscles, whereas the redundant activities of
      group Ia/II and group Ib afferents appear to determine the pattern of extensor
      muscle firing. These findings establish a role for proprioceptive feedback in the
      control of fundamental aspects of mammalian locomotor behavior. 

PMID- 25389310
TI  - Flexible and conductive MXene films and nanocomposites with high capacitance.
AB  - MXenes, a new family of 2D materials, combine hydrophilic surfaces with metallic
      conductivity. Delamination of MXene produces single-layer nanosheets with
      thickness of about a nanometer and lateral size of the order of micrometers. The
      high aspect ratio of delaminated MXene renders it promising nanofiller in
      multifunctional polymer nanocomposites. Herein, Ti3C2T(x) MXene was mixed with
      either a charged polydiallyldimethylammonium chloride (PDDA) or an electrically
      neutral polyvinyl alcohol (PVA) to produce Ti3C2T(x)/polymer composites. The as
      fabricated composites are flexible and have electrical conductivities as high as
      2.2 * 10(4) S/m in the case of the Ti3C2T(x)/PVA composite film and 2.4 * 10(5)
      S/m for pure Ti3C2T(x) films. The tensile strength of the Ti3C2T(x)/PVA
      composites was significantly enhanced compared with pure Ti3C2T(x) or PVA films.
      The intercalation and confinement of the polymer between the MXene flakes not
      only increased flexibility but also enhanced cationic intercalation, offering an
      impressive volumetric capacitance of ~530 F/cm(3) for MXene/PVA-KOH composite
      film at 2 mV/s. To our knowledge, this study is a first, but crucial, step in
      exploring the potential of using MXenes in polymer-based multifunctional
      nanocomposites for a host of applications, such as structural components, energy
      storage devices, wearable electronics, electrochemical actuators, and
      radiofrequency shielding, to name a few.

PMID- 25389311
TI  - Transcriptional program of Kpna2/Importin-alpha2 regulates cellular
      differentiation-coupled circadian clock development in mammalian cells.
AB  - The circadian clock in mammalian cells is cell-autonomously generated during the
      cellular differentiation process, but the underlying mechanisms are not
      understood. Here we show that perturbation of the transcriptional program by
      constitutive expression of transcription factor c-Myc and DNA methyltransferase 1
      (Dnmt1) ablation disrupts the differentiation-coupled emergence of the clock from
      mouse ESCs. Using these model ESCs, 484 genes are identified by global gene
      expression analysis as factors correlated with differentiation-coupled circadian
      clock development. Among them, we find the misregulation of Kpna2 (Importin
      alpha2) during the differentiation of the c-Myc-overexpressed and Dnmt1(-/-)
      ESCs, in which sustained cytoplasmic accumulation of PER proteins is observed.
      Moreover, constitutive expression of Kpna2 during the differentiation culture of
      ESCs significantly impairs clock development, and KPNA2 facilitates cytoplasmic
      localization of PER1/2. These results suggest that the programmed gene expression
      network regulates the differentiation-coupled circadian clock development in
      mammalian cells, at least in part via posttranscriptional regulation of clock
      proteins. 

PMID- 25389312
TI  - Human TRPA1 is intrinsically cold- and chemosensitive with and without its N
      terminal ankyrin repeat domain.
AB  - We have purified and reconstituted human transient receptor potential (TRP)
      subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to
      understand its inherent thermo- and chemosensory properties as well as the role
      of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We
      report that hTRPA1 with and without its N-terminal ARD (Delta1-688 hTRPA1) is
      intrinsically cold-sensitive, and thus, cold-sensing properties of hTRPA1 reside
      outside the N-terminal ARD. We show activation of hTRPA1 by the thiol oxidant 2
      ((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin) and that
      electrophilic compounds activate hTRPA1 in the presence and absence of the N
      terminal ARD. The nonelectrophilic compounds menthol and the cannabinoid Delta(9)
      tetrahydrocannabiorcol (C16) directly activate hTRPA1 at different sites
      independent of the N-terminal ARD. The TRPA1 antagonist HC030031 inhibited cold
      and chemical activation of hTRPA1 and Delta1-688 hTRPA1, supporting a direct
      interaction with hTRPA1 outside the N-terminal ARD. These findings show that
      hTRPA1 is an intrinsically cold- and chemosensitive ion channel. Thus, second
      messengers, including Ca(2+), or accessory proteins are not needed for hTRPA1
      responses to cold or chemical activators. We suggest that conformational changes
      outside the N-terminal ARD by cold, electrophiles, and nonelectrophiles are
      important in hTRPA1 channel gating and that targeting chemical interaction sites
      outside the N-terminal ARD provides possibilities to fine tune TRPA1-based drug
      therapies (e.g., for treatment of pain associated with cold hypersensitivity and
      cardiovascular disease). 

PMID- 25389316
TI  - Role of polysomnography in the development of an algorithm for planning
      tracheostomy decannulation.
AB  - OBJECTIVE: To examine the role of polysomnography (PSG) in helping determine
      readiness of tracheostomized patients for decannulation. STUDY DESIGN: Case
      series with chart review of pediatric patients who underwent PSG with
      tracheostomy tube in place with the goal of decannulation. SETTING: Tertiary care
      pediatric center. SUBJECTS AND METHODS: Twenty-eight tracheostomized patients who
      underwent PSG from January 2006 to March 2012 were included. Outcome measures
      were successful decannulation, PSG results, surgical procedures, and medical
      comorbidities. RESULTS: Of the 28 patients, 20 (71.4%) were decannulated and 8
      (28.6%) were not. One (3.6%) patient failed long-term decannulation. The average
      apnea-hypopnea index (AHI) with a capped tracheostomy for those successfully
      decannulated was 2.75 (range, 0.6-7.6), while the AHI for those not decannulated
      was 15.99 (range, 3.2-62). Factors associated with success or failure to
      decannulate were assessed, and an algorithm was developed to plan for successful
      decannulation. Laryngotracheal reconstruction was a significant factor in those
      successfully decannulated. Those who were not decannulated had multiple medical
      comorbidities, multilevel airway obstruction, need for additional surgery, or
      chronic need for pulmonary toilet. CONCLUSIONS: Polysomnography may be a useful
      adjunctive study in the process of determining a patient's readiness for
      decannulation. Our current algorithm for decannulation includes upper airway
      endoscopy with identification of levels of obstruction, followed by surgical
      correction of those obstructions; capped PSG to determine patency of the airway
      and help assess lung function; and overnight intensive care unit admission for
      capping trial, with decannulation the following day if well tolerated.

PMID- 25389315
TI  - Loss of microRNA-106b-25 cluster promotes atrial fibrillation by enhancing
      ryanodine receptor type-2 expression and calcium release.
AB  - BACKGROUND: Enhanced sarcoplasmic reticulum Ca(2+)-leak via ryanodine receptor
      type-2 (RyR2) contributes to the pathogenesis of atrial fibrillation (AF). Recent
      studies have shown that the level of RyR2 protein is elevated in atria of
      patients with paroxysmal AF, suggesting that microRNA-mediated post
      transcriptional regulation of RyR2 might be an underlying mechanism.
      Bioinformatic analysis suggests that miR-106b and miR-93, members of the miR-106b
      25 cluster, could bind to RyR2-3'-untranslated region and suppress its
      translation. Thus, we tested the hypothesis that loss of the miR-106b-25 cluster
      promotes AF via enhanced RyR2-mediated sarcoplasmic reticulum Ca(2+)-leak.
      METHODS AND RESULTS: Quantitative real-time polymerase chain reaction showed that
      the levels of mature miR-106b, miR-93, and miR-25 were lower in atria of patients
      with paroxysmal AF when compared with patients in sinus rhythm. In vitro assay
      showed that miR-93 reduced RyR2-3'-untranslated region luciferase activity. Total
      RyR2 protein in atrial tissue of miR-106b-25(-/-) mice was increased by 42% when
      compared with wild-type littermates but still maintained a normal subcellular
      distribution. Ca(2+)-spark frequency and total sarcoplasmic reticulum Ca(2+)-leak
      were increased in atrial myocytes of miR-106b-25(-/-) mice. Telemetry ECG
      recordings revealed that miR-106b-25(-/-) mice exhibited more frequent atrial
      ectopy and were also more susceptible to pacing-induced AF than wild-type
      littermates. Increased sarcoplasmic reticulum Ca(2+)-release and AF
      susceptibility in miR-106b-25(-/-) mice were abolished by the RyR2 blocker K201.
      CONCLUSIONS: These results suggest that miR-106b-25 cluster-mediated post
      transcriptional regulation of RyR2 is a potential molecular mechanism involved in
      paroxysmal AF pathogenesis. As such, the miR-106b-25 cluster could be a novel
      gene-therapy target in AF associated with enhanced RyR2 expression.

PMID- 25389317
TI  - Epithelial-mesenchymal transition: clinical implications for nodal metastasis and
      prognosis of tongue cancer.
AB  - OBJECTIVE: The development of biomarkers for the prediction of lymph node
      metastasis and prognosis is critical for deciding the treatment modality of
      tongue cancer. The purpose of our study is to investigate the clinical
      implications of epithelial-mesenchymal transition (EMT) expression in tongue
      cancer. STUDY DESIGN: Historical cohort study SETTING: Tertiary-care hospital.
      SUBJECTS AND METHODS: The study included 95 subjects with tongue cancer who
      underwent wide excision and neck dissection. According to characteristics of
      immunohistochemical staining for E-cadherin and vimentin, we classified the
      tumors as complete EMT phenotype, incomplete EMT phenotype, or epithelial
      phenotype. The correlation between risk factors and nodal metastasis was
      assessed, and disease-free survival (DFS) was analyzed. RESULTS: Positive lymph
      nodes were detected in 46 (48.4%) patients and was found to correlate
      significantly with depth of invasion >= 4 mm and EMT expression on multivariate
      analysis (P = .030, P = .022, respectively). The mean follow-up period of all
      patients was 96.3 months (range, 6-149 months). Overall 5-year DFS was 61.7%. On
      multivariate analysis, the only factors affecting DFS were nodal stage and EMT
      expression (P = .033, P = .021, respectively). CONCLUSIONS: Our study reveals
      that EMT expression is a significant biomarker for predicting lymph node
      metastasis and tumor recurrence in tongue cancer. Evaluation of EMT expression in
      tongue cancer can allow therapy to be offered accordingly.

PMID- 25389318
TI  - Lymphedema outcomes in patients with head and neck cancer.
AB  - OBJECTIVE: We sought to describe the presentation of external head and neck
      lymphedema in patients treated for head and neck cancer and to examine their
      initial responses to complete decongestive therapy. STUDY DESIGN: Case series
      with chart review. SETTING: MD Anderson Cancer Center, Houston, Texas. SUBJECTS
      AND METHODS: The charts of patients who were evaluated for head and neck cancer
      at MD Anderson Cancer Center after treatment (January 2007-January 2013) were
      retrospectively reviewed. Response to complete decongestive therapy was evaluated
      per changes in lymphedema severity rating or surface tape measures. Predictors of
      therapy response were examined on the basis of regression models. RESULTS: The
      cases of 1202 patients were evaluated. Most patients (62%) had soft reversible
      pitting edema (MD Anderson Cancer Center stage 1b). Treatment response was
      evaluated for 733 patients; 439 (60%) improved after complete decongestive
      therapy. Treatment adherence independently predicted complete decongestive
      therapy response (P < .001). CONCLUSIONS: These data support the effectiveness of
      a head and neck cancer-specific regimen of lymphedema therapy for cancer patients
      with external head and neck lymphedema. Our findings suggest that head and neck
      lymphedema is distinct from lymphedema that affects other sites, thus requiring
      adaptations in traditional methods of management and measurement.

PMID- 25389319
TI  - Expert witness testimony guidelines: identifying areas for improvement.
AB  - Expert witnesses play an invaluable, if controversial, role by deciphering
      medical events for juries in cases of alleged negligence. We review expert
      witness guidelines among major surgical societies and identify gaps within these
      standards, as our hope is that this spurs discussion addressing areas for
      improvement. Of 8 surgical societies with accessible guidelines, none included
      specific compensation guidelines or limits, detailed reporting mechanisms
      regarding unethical behavior by legal professionals, or addressed the
      appropriateness of testifying frequently and exclusively for one side. Several
      processes possibly deterring grossly inaccurate testimony have been adopted by
      other surgical societies and should potentially be addressed by the American
      Academy of Otolaryngology-Head and Neck Surgery. These include offering an expert
      witness testimony certification path, strengthening the formalized grievance
      process, and encouraging members to sign an affirmation statement. 

PMID- 25389320
TI  - Voice assessment and voice-related quality of life in patients with benign
      thyroid disease.
AB  - OBJECTIVE: To identify the relationship between vocal self-assessment, the
      assessment of voice by a speech-language pathologist (SLP), and the effect of
      voice on the quality of life of patients with benign thyroid diseases. STUDY
      DESIGN: Cross-sectional study. SETTING: University hospital. SUBJECTS AND METHOD:
      A total of 67 women with a mean age of 44.7 +/- 14.8 years and a diagnosis of
      benign thyroid disease were included in the study. Vocal self-assessment and SLP
      assessment were performed using a visual analogue scale (VAS). The Voice-related
      Quality of Life Questionnaire (V-RQOL) was used to identify the effect of voice
      on quality of life. The Mann-Whitney and Kruskal-Wallis nonparametric tests were
      used. Correlations between assessments were verified by the Spearman correlation
      test. The significance level was 5%. RESULTS: Patients with vocal complaints had
      lower scores in all assessments. Patients with thyroid nodules performed worse on
      the SLP assessment and on the physical functioning domain of V-RQOL. A moderate
      correlation was found between the self-assessment and quality of life and between
      the physical functioning domain of V-RQOL and the SLP assessment. A weak
      correlation existed between the self-assessment and the SLP assessment.
      CONCLUSION: Patients with benign thyroid diseases had lower scores in vocal self
      assessment, the clinical evaluation of voice, and the V-RQOL. These dimensions of
      voice assessment showed correlations ranging from mild to moderate and should
      complement the clinical routine.

PMID- 25389321
TI  - Diagnostic yield of MRI for pediatric hearing loss: a systematic review.
AB  - OBJECTIVE: To perform a systematic review to analyze the diagnostic yield of
      magnetic resonance imaging (MRI) for pediatric hearing loss, including comparison
      to computed tomography (CT) and subgroup evaluation according to impairment
      severity and specific diagnostic findings (cochlear anomalies, enlarged
      vestibular aqueduct, cochlear nerve abnormalities, and brain findings). DATA
      SOURCES: Pubmed, EMBASE, and the Cochrane library were assessed from their
      inception through December 2013. Manual searches were also performed, and topic
      experts were contacted. REVIEW METHODS: Data from studies describing the use of
      MRI with or without comparison to CT in the diagnostic evaluation of pediatric
      patients with hearing loss were evaluated, according to a priori
      inclusion/exclusion criteria. Two independent evaluators corroborated the
      extracted data. Heterogeneity was evaluated according to the I(2) statistic.
      RESULTS: There were 29 studies that evaluated 2434 patients with MRIs and 1451
      patients with CTs that met inclusion/exclusion criteria. There was a wide range
      of diagnostic yield from MRI. Heterogeneity among studies was substantial but
      improved with subgroup analysis. Meta-analysis of yield differences demonstrated
      that CT had a greater yield than MRI for enlarged vestibular aqueduct (yield
      difference 16.7% [95% CI, 9.1%-24.4%]) and a borderline advantage for cochlear
      anomalies (4.7% [95% CI, 0.1%-9.5%]). Studies were more likely to report brain
      findings with MRI. CONCLUSIONS: These data may be utilized in concert with that
      from studies of risks of MRI and risk/yield of CT to inform the choice of
      diagnostic testing.

PMID- 25389322
TI  - Role of direct laryngoscopy and bronchoscopy in recurrent croup.
AB  - OBJECTIVE: To determine risk factors in children with recurrent croup that
      predict moderate/severe findings on direct laryngoscopy and bronchoscopy and need
      for further operative interventions. STUDY DESIGN: Retrospective chart review
      cohort. SETTING: Tertiary care children's hospital. SUBJECTS AND METHODS:
      Retrospective chart review of 103 patients diagnosed with recurrent croup who
      underwent diagnostic laryngoscopy and bronchoscopy from January 2004 to August
      2013. Statistical analysis determined risk factors significantly associated with
      moderate/severe operative findings. A probability tree was formulated. RESULTS:
      Of 103 patients, 30.1% had history of intubation, 6.8% had a history of
      subglottic stenosis, 6.8% had a history of previous airway procedure, 11.7%
      consultations were inpatient, 64.1% had asthma, 47.6% had seasonal allergies,
      60.2% had gastroesophageal reflux disease, 15.5% were aged <= 12 months, and
      51.5% were <= 36 months. Statistically significant risk factors in predicting
      moderately/severely abnormal operative findings included consultation location (P
      = .010), history of intubation (P = .003), age younger than 36 months (P = .013),
      and seasonal allergies (P = .035). When using location of consultation, history
      of intubation, and age in a statistical model, diagnostic accuracy equaled 93.5%.
      Of children without history of intubation but who underwent inpatient
      otolaryngology consultation, 28.6% had moderate/severe findings. Likewise, 41.2%
      of children with a history of intubation who were younger than 36 months of age
      had moderate/severe findings. CONCLUSION: Moderate to severe operative findings
      are encountered in only 8.7% of children with recurrent croup. Using statistical
      modeling, 2 high-risk groups are (1) patients without a history of intubation but
      inpatient consultation and (2) patients with a history of intubation and age
      younger than 36 months.

PMID- 25389323
TI  - The challenge of integrating informatics training during residency.

PMID- 25389325
TI  - Primary care physicians and the laboratory: now and the future.

PMID- 25389324
TI  - Napsin A: Another milestone in the subclassification of ovarian carcinoma.

PMID- 25389326
TI  - The next chapter in patient blood management: real-time clinical decision
      support.
AB  - OBJECTIVES: Blood transfusion was identified by the American Medical Association
      as one of the top five most frequently overused therapies. Utilization review has
      been required by accreditation agencies, but retrospective review has been
      ineffective due to labor-intense resources applied to only a sampling of
      transfusion events. Electronic medical records have allowed clinical decision
      support (CDS) to occur via a best practices alert at the critical decision point
      concurrently with physician order entry. METHODS: We review emerging strategies
      for improving blood utilization. RESULTS: Implementation of CDS at our
      institution decreased the percentage of transfusions in patients with a
      hemoglobin level of more than 8 g/dL from 60% to less than 30%. Annual RBC
      transfusions were reduced by 24%, despite concurrent increases in patient
      discharge volumes and case mix complexity. This resulted in acquisition costs
      savings (direct blood product purchase costs) of $6.4 million over 4 years.
      CONCLUSIONS: We have been able to significantly reduce inappropriate blood
      transfusions and related costs through an educational initiative coupled with
      real-time CDS. In deriving increased value out of health care, CDS can be applied
      to a number of overuse measures in laboratory testing, radiology, and therapy
      such as antibiotics, as outlined by the American Board of Internal Medicine's
      Choosing Wisely campaign.

PMID- 25389327
TI  - Longitudinal engagement of pathology residents: a proposed approach for
      informatics training.
AB  - OBJECTIVES: The intersecting of pathology training and practice and the
      utilization of information technology has become an increasingly common
      occurrence, and the most effective means of teaching residents informatics during
      these invaluable years has yet to be firmly established. METHODS: In offering the
      idea of longitudinal engagement that stresses early and extended trainee
      involvement, we attempt to provide a different manner of helping address some of
      the leading time-limited issues surrounding education in informatics. RESULTS:
      The proposed model is intended to allow building off a base of fundamentals
      reached through introductory didactics, exposure to and active participation in
      departmental and hospital-wide administrative bodies, refining of initial skills
      gained through frequent mentoring and coaching, and combining these cumulative
      knowledge and experiential underpinnings with graduated responsibility in a
      particular area of expertise. CONCLUSIONS: In transforming the ways in which
      pathology residencies teach their trainees informatics, the prospects of
      realizing its potential utility are heightened.

PMID- 25389328
TI  - HER2 heterogeneity affects trastuzumab responses and survival in patients with
      HER2-positive metastatic breast cancer.
AB  - OBJECTIVES: Heterogeneity of HER2 gene amplification is found in a subset of
      breast cancers. We investigated the impact of HER2 heterogeneity on trastuzumab
      responses and clinical outcomes in 112 patients with HER2-positive metastatic
      breast cancer. METHODS: Regional and genetic heterogeneity of HER2 gene
      amplification was determined in three different areas of each tumor by
      immunohistochemistry and silver in situ hybridization. We also assessed the
      overall levels of HER2 amplification and the proportion of tumor cells with a
      HER2/CEP17 ratio of more than 2.2 or strong and complete membranous (3+)
      expression of HER2 protein. RESULTS: HER2 regional and genetic heterogeneity
      based on the HER2/CEP17 ratio was confirmed in 8.7% and 2.7% of cases,
      respectively. Poor response to trastuzumab was associated with overall low-level
      or equivocal amplification, HER2 regional heterogeneity by the HER2/CEP17 ratio,
      the HER2/CEP17 ratio of more than 2.2 in less than 80% of tumor cells, and HER2
      immunohistochemical expression of 3+ in less than 75% of tumor cells. In survival
      analyses, low-level or equivocal HER2 amplification, HER2 regional heterogeneity
      based on the HER2/CEP17 ratio, and the HER2/CEP17 ratio of more than 2.2 in less
      than 80% of tumor cells were associated with shorter time to progression and
      lower overall survival in univariate and multivariate analyses. CONCLUSIONS:
      These results suggest that accurate assessment of HER2 status, including HER2
      heterogeneity, is important in predicting trastuzumab responses and outcomes in
      patients with HER2-positive metastatic breast cancer.

PMID- 25389329
TI  - p16INK4a immunohistochemistry in cervical biopsy specimens: A systematic review
      and meta-analysis of the interobserver agreement.
AB  - OBJECTIVES: The interpretation of cervical biopsy specimens guides management of
      women with suspected cervical cancer precursors. However, morphologic evaluation
      is subjective and has low interobserver agreement. Addition of p16(INK4a)
      immunohistochemistry may improve interpretation. METHODS: We performed a
      systematic review and meta-analysis of published data on interobserver agreement
      of p16(INK4a) positivity using p16(INK4a) immunohistochemistry and of cervical
      intraepithelial neoplasia grade 2 (CIN2+) and CIN grade 3 (CIN3+) classification
      using H&E morphology in conjunction with p16(INK4a) in comparison with H&E
      morphology alone. RESULTS: The literature search revealed five eligible articles.
      The results show strong agreement of pathologists' interpretation of cervical
      biopsy specimens as p16(INK4a) positive or negative (pooled kappa = 0.90; 95%
      confidence interval [CI], 0.88-0.92) and significantly higher agreement for a
      CIN2+ diagnosis with H&E morphology in conjunction with p16(INK4a) (kappa = 0.73;
      95% CI, 0.67-0.79) compared with H&E morphology alone (kappa = 0.41; 95% CI, 0.17
      0.65). Also, a slightly higher agreement for CIN3+ can be observed (kappa = 0.66;
      95% CI, 0.39-0.94 for H&E morphology in conjunction with p16(INK4a) and kappa =
      0.61; 95% CI, 0.44-0.78 for H&E morphology alone), but this difference was not
      statistically significant. CONCLUSIONS: The published literature indicates
      improved interobserver agreement of the diagnosis of CIN2+ with the conjunctive
      use of H&E morphology with p16(INK4a) immunohistochemistry compared with H&E
      morphology alone.

PMID- 25389330
TI  - Cancer tracking: Clinician compliance and program outcome.
AB  - OBJECTIVES: Certain laboratory tests are critical for patient care and must be
      communicated rapidly. Professional societies have developed guidelines for
      reporting of "critical values" and significant or unexpected surgical pathology
      findings. Urgent diagnoses requiring rapid reporting include new or unexpected
      diagnoses of malignancy. The University of Missouri established a "cancer
      tracking" protocol in which all diagnoses of malignancy require acknowledgment by
      the responsible clinician. METHODS: We reviewed 5 months of compliance with the
      cancer-tracking protocol. The protocol requires the Department of Pathology to
      send a letter to the responsible clinician requesting acknowledgment of the
      report. In total, 1,155 confirmation requests were sent to the physicians named
      on the request form. RESULTS: Following the first letter, 692 acknowledgments
      were received, and 356 acknowledgments followed the second letter. In 107 (9%)
      cases, no response was received. CONCLUSIONS: Confirmation that the physician
      caring for a patient receives a pathology diagnosis is important for patient
      management and quality assurance. While the surgical pathology report was placed
      in the chart, it was impossible to confirm that the responsible physician had
      reviewed the report in 9% of cases. Techniques for communication and confirmation
      of transmission of anatomic pathology diagnoses need to be developed.

PMID- 25389331
TI  - Development and validation of effective real-time and periodic interinstrument
      comparison method for automatic hematology analyzers.
AB  - OBJECTIVES: We developed and validated an interinstrument comparison method for
      automatic hematology analyzers based on the 99th percentile coefficient of
      variation (CV) cutoff of daily means and validated in both patient samples and
      quality control (QC) materials. METHODS: A total of 120 patient samples were
      obtained over 6 months. Data from the first 3 months were used to determine 99th
      percentile CV cutoff values, and data obtained in the last 3 months were used to
      calculate acceptable ranges and rejection rates. Identical analyses were also
      performed using QC materials. Two instrument comparisons were also performed, and
      the most appropriate allowable total error (ATE) values were determined. RESULTS:
      The rejection rates based on the 99th percentile cutoff values were within 10.00%
      and 9.30% for the patient samples and QC materials, respectively. The acceptable
      ranges of QC materials based on the currently used method were wider than those
      calculated from the 99th percentile CV cutoff values in most items. In two
      instrument comparisons, 34.8% of all comparisons failed, and 87.0% of failed
      comparisons were successful when 4 SD was applied as an ATE value instead of 3
      SD. CONCLUSIONS: The 99th percentile CV cutoff value-derived daily acceptable
      ranges can be used as a real-time interinstrument comparison method in both
      patient samples and QC materials. Applying 4 SD as an ATE value can significantly
      reduce unnecessarily followed recalibration in the leukocyte differential counts,
      reticulocytes, and mean corpuscular volume.

PMID- 25389332
TI  - Epstein-Barr virus-positive pleural effusion: Clinical features, cytomorphologic
      characteristics, and flow cytometric immunophenotyping.
AB  - OBJECTIVES: The etiology of pleural effusions (PEs) varies, and a percentage of
      PEs remains unexplained despite an intensive workup. One previous study
      documented a high prevalence of Epstein-Barr virus (EBV)-DNA in unselected and
      unexplained PEs. Our aim is to characterize the clinical and cytomorphologic
      features of EBV-associated PEs, which have not been described. METHODS: A
      database search was performed for PEs with EBV-DNA identified in the fluid by
      real-time quantitative polymerase chain reaction. The corresponding fluid
      cytology and chemistry were reviewed, and the patients' demographic data and
      clinical features were recorded. RESULTS: A total of 20 cases of EBV-DNA-positive
      PE were found. All patients had a history of lung transplantation. Most of the PE
      EBV loads were relatively low. Cytologically, polymorphous lymphocytosis was
      present in more than 70% of PEs. Scattered lymphocytic mitosis and apoptosis were
      seen in some cases. Mesothelial cells varied in number, and some cases showed
      reactive atypia. The lymphocytes were predominantly T cells with the CD4/CD8
      ratio varying from 10:1 to 3:20. CONCLUSIONS: EBV infection/reactivation can
      account for certain proportions of "idiopathic" PEs. Polymorphous lymphocytosis
      is the most common cytologic feature, but atypical features (in both lymphocytes
      and mesothelial cells) can be seen.

PMID- 25389333
TI  - Mesenchymal stromal cell density is increased in higher grade myelodysplastic
      syndromes and independently predicts survival.
AB  - OBJECTIVES: We retrospectively tested the prognostic and diagnostic significance
      of CD271+ mesenchymal stromal cell (MSC) density in cytopenic patients who
      underwent bone marrow biopsy to evaluate for myelodysplastic syndromes (MDS).
      METHODS: CD271+ MSC density was quantitated by automated image analysis of tissue
      microarray cores in 125 cytopenic patients: 40 lower grade MDS (<5% marrow
      blasts), 24 higher grade MDS, and 61 benign. RESULTS: CD271+ MSC density was
      increased in higher grade MDS compared with benign (P = .006) and lower grade MDS
      (P = .02). CD271+ MSC density was predictive of survival among patients with MDS
      independent of Revised International Prognostic Scoring System (IPSS-R), history
      of transfusion, therapy-related MDS, and fibrosis (hazard ratio, 3.4; P < .001).
      Among low or intermediate IPSS-R patients, median survival was significantly
      shorter in the high CD271+ MSC density group (47 vs 18 months, P < .02).
      CONCLUSIONS: High CD271+ MSC density is characteristic of higher grade MDS and is
      associated with poor risk independent of known prognostic factors.

PMID- 25389334
TI  - Mixed phenotype acute leukemia: A study of 61 cases using World Health
      Organization and European Group for the Immunological Classification of
      Leukaemias criteria.
AB  - OBJECTIVES: The 2008 World Health Organization (WHO) classification system
      grouped bilineal and biphenotypic acute leukemias together under a new heading of
      mixed phenotype acute leukemia (MPAL). The lineage-specific marker criteria have
      also changed for a diagnosis of MPAL. The goal of this study was to characterize
      clinical significance of this new group. METHODS: Sixty-one patients diagnosed
      with MPAL using either European Group for the Immunological Classification of
      Leukaemias (EGIL) criteria or 2008 WHO criteria were included in this study.
      RESULTS: Sixteen patients (26%) diagnosed with acute biphenotypic leukemia using
      EGIL criteria did not fulfill 2008 WHO criteria for MPAL. Cytogenetic data were
      available for 32 patients, and the most common abnormality was t(9;22) (five of
      32 cases). Clinical outcome data suggested that younger patients with MPAL (<=21
      years) had better overall survival (OS) in both the EGIL and WHO groups (EGIL, P
      = .0403; WHO, P = .0601). Compared with 177 patients with acute myeloid leukemia
      (AML), MPAL patients had better OS (P = .0003) and progression-free survival (P =
      .0001). However, no difference in OS between MPAL and 387 patients with acute
      lymphoblastic leukemia was present (P = .599). CONCLUSIONS: As defined by the
      2008 WHO classification, fewer patients are now classified as having MPAL than
      with the EGIL criteria. In this study, patients with MPAL have a better clinical
      outcome compared with patients with AML.

PMID- 25389335
TI  - Circulating donor-specific anti-human leukocyte antigen antibodies and complement
      C4d deposition are associated with the development of cardiac allograft
      vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) continues to be a limiting
      factor in long-term survival of heart transplant recipients (HTRs).
      Pathophysiologic and immunologic factors affecting CAV are complex, and criteria
      for early diagnosis remain elusive. METHODS: We performed a retrospective
      analysis of the relationship between donor-specific antibody (DSA), C4d
      immunofluorescence, and the development of CAV. RESULTS: We evaluated 330
      endomyocardial biopsy (EMB) specimens from 112 cardiac grafts. Twenty-four (21%)
      of 112 grafts developed CAV, and 18 (75%) of 24 were positive for C4d. Patients
      with DSA (n = 51) against human leukocyte antigen class I (n = 5), II (n = 26),
      or both (n = 20) developed CAV at a rate of 40%, 38%, and 20% and a mean time to
      CAV of 89, 47, and 25 months, respectively. Of 61 grafts without DSA, only 13%
      developed CAV, with a mean time to CAV of 116 months. CONCLUSIONS: Compared with
      the general HTR population, patients with graft dysfunction and DSA or positive
      C4d on EMB show a statistically significant increased incidence of CAV and
      allograft failure, suggesting an antibody-mediated injury. The presence of pre-
      and posttransplant DSA, even in the absence of positive C4d immunofluorescence,
      may identify a group of HTRs at increased risk of developing CAV.

PMID- 25389336
TI  - Diverse clinicopathologic features in human herpesvirus 8-associated lymphomas
      lead to diagnostic problems.
AB  - OBJECTIVES: Human herpesvirus 8 (HHV8)-associated lymphomas are uncommon, mainly
      affect men infected with the human immunodeficiency virus (HIV), and usually have
      a poor prognosis. We sought to characterize the HHV8+ lymphomas seen at our
      institution since the mid-1990s. METHODS: We identified 15 patients with HHV8
      associated lymphomas and evaluated their clinical and pathologic features.
      RESULTS: Diagnoses included primary effusion lymphoma (PEL) (n = 2),
      extracavitary PEL (n = 8), intravascular large B-cell lymphoma (n = 1), HHV8+
      plasmablastic microlymphoma (n = 3), and germinotropic lymphoproliferative
      disorder (GLD) (n = 1). The case of GLD progressed to a high-grade HHV8+ Epstein
      Barr virus-positive lymphoma, an evolution that has not been previously reported.
      Four patients were HIV-(three from an HHV8-endemic area). Potentially misleading
      pathologic features in our series of extracavitary PEL included classic Hodgkin
      lymphoma-like features, lymph node sinus involvement, and T-cell antigen
      expression. CONCLUSIONS: HHV8-associated lymphomas can be clinically and
      pathologically heterogeneous, with features that may lead to misdiagnosis as
      other types of lymphoma.

PMID- 25389337
TI  - The lung-restricted marker napsin A is highly expressed in clear cell carcinomas
      of the ovary.
AB  - OBJECTIVES: We recently observed expression of the "lung" marker napsin A in
      ovarian clear cell carcinomas and therefore sought to determine the extent of
      napsin A expression in a subset of ovarian neoplasms. METHODS: We identified an
      archival series of ovarian clear cell carcinomas (n = 36), serous borderline
      tumors (n = 21), high-grade serous carcinomas (n = 37), and endometrioid
      adenocarcinomas (n = 29). Using standard immunohistochemical techniques on whole
      sections of formalin-fixed, paraffin-embedded specimens, we employed a panel of
      antibodies: napsin A (IP64), estrogen receptor (SP1), WT-1 (6F-H2), PAX-8 (BC12),
      and TTF-1 (SPT24). RESULTS: Thirty-six of 36 clear cell carcinomas showed napsin
      A expression, typically in a uniform pattern. None of the serous borderline
      tumors or high-grade serous carcinomas manifested napsin A expression. Napsin A
      was expressed in three (10%) of 29 endometrioid adenocarcinomas, generally in a
      focal pattern. CONCLUSIONS: Our study showed that napsin A is an extremely
      sensitive (100%) marker of ovarian clear cell carcinomas and exhibits very high
      specificity (100%) in distinguishing clear cell carcinomas from high-grade serous
      carcinomas and serous borderline tumors and 90% specificity in discriminating
      clear cell carcinomas from endometrioid carcinomas.

PMID- 25389338
TI  - Differential expression of CD200 in B-cell neoplasms by flow cytometry can assist
      in diagnosis, subclassification, and bone marrow staging.
AB  - OBJECTIVES: To analyze CD200 expression by flow cytometry in a large series of B
      cell neoplasms in a variety of tissue types in comparison with benign B-lineage
      cells. METHODS: We measured CD200 expression levels in 505 peripheral blood (PB),
      bone marrow (BM), and lymphoid tissue biopsy specimens, including 364 cases
      positive for B-cell leukemias and lymphomas. RESULTS: CD200 expression in chronic
      lymphocytic leukemia cases was as bright as or brighter than normal PB B cells in
      nearly all cases, while mantle cell lymphoma (MCL) cases were usually dim or
      negative. However, rare MCL cases (about 5%) were moderately bright for CD200.
      Marginal zone lymphomas varied by subtype, with nodal cases brighter, splenic
      cases dimmer, and extranodal cases heterogeneous for CD200 expression. Follicular
      lymphoma (FL) cells were brighter for CD200 in BM specimens than in lymph nodes.
      In some BM specimens, dim CD200 could distinguish FL cells from background
      hematogones. Large B-cell lymphomas of the non-germinal center type tended to be
      brighter for CD200 than those of the germinal center type, while Burkitt
      lymphomas were negative. CONCLUSIONS: CD200 staining by flow cytometry can be
      useful in the differential diagnosis of B-cell neoplasms and in their detection
      in the BM.

PMID- 25389339
TI  - Prognostic stratification of ulcerated melanoma: not only the extent matters.
AB  - OBJECTIVES: For patients with melanoma, ulceration is an important prognostic
      marker and interestingly also a predictive marker for the response of adjuvant
      interferon. A consensual definition and accurate assessment of ulceration are
      therefore crucial for proper staging and clinical management. We evaluated the
      prognostic impact of the extent and type of ulceration and the epidermal
      involvement theoretically preceding it (consumption of epidermis and cleft
      formation) or seen subsequent to the inflammation (reepithelialization and
      reactive epidermal hyperplasia), aiming for better prognostic stratification of
      ulcerated lesions. METHODS: From H&E-stained sections, the status (presence vs
      absence), extent (percentage of the total tumor length), and type (infiltrative
      vs attenuative) of ulceration and epidermal involvement were evaluated from 385
      patients with cutaneous melanoma. RESULTS: The presence of ulceration (hazard
      ratio [HR], 1.83), an attenuative type of ulceration (HR, 3.02), and excessive
      ulceration (HR, 3.57) were independent predictors of poor melanoma-specific
      survival. Further subdivision of minimal/moderate ulceration showed independent
      prognostic value only for lesions with epidermal involvement of the surrounding
      epidermis (HR, 1.78). CONCLUSION: The extent and type of ulceration and
      involvement of the surrounding epidermis provided more accurate prognostic
      information than the mere absence or presence and may be useful markers allowing
      better stratification of ulcerated lesions.

PMID- 25389340
TI  - Method precision and frequent causes of errors observed in point-of-care glucose
      testing: a proficiency testing program perspective.
AB  - OBJECTIVES: Method imprecision, error rates, and explanatory causes that were
      identified in the Institute for Quality Management in Healthcare point-of-care
      (POC) glucose proficiency testing (PT) program were assessed in comparison with
      results obtained from laboratory glucose PT surveys. METHODS: POC and laboratory
      glucose PT data were assessed from September 2009 to June 2011. Peer group means
      and coefficients of variation (CVs) were estimated using the robust algorithm
      recommended in the International Organization for Standardization/International
      Electrotechnical Commission 13528(E). Discordant finding investigations were also
      reviewed to determine the causes of significant and recurring errors. RESULTS:
      POC glucose CVs were higher than laboratory method CVs (median CV, 4.5% and 1.6%,
      respectively). While all laboratory glucose results were within the performance
      limits, 305 (0.59%) of 51,379 POC glucose results exceeded limits. Investigations
      were required for 277 (0.53%) POC results. Pre- and postanalytical errors
      accounted for 76% of the discordant findings. Using wrong PT items, sample mix-up
      on the bench, and reporting results for the wrong sample were the most frequent
      reasons, while 21% of discordant findings identified manufacturer issues, and 3%
      were of unknown origin. CONCLUSIONS: Both method CVs and error rates were higher
      in POC than in laboratory glucose methods, even though larger performance limits
      were used for the assessment of POC glucose.

PMID- 25389341
TI  - Uroplakin II is a more sensitive immunohistochemical marker than uroplakin III in
      urothelial carcinoma and its variants.
AB  - OBJECTIVES: Uroplakin (UP) II and UPIII are highly specific immunohistochemical
      markers for urothelial differentiation. Here we studied the sensitivity of UPII
      and UPIII in conventional and variant urothelial carcinomas (UCs). METHODS:
      Immunohistochemical staining for UPII and UPIII was performed on tissue
      microarray slides, including 105 conventional bladder UCs (BUCs), 90 upper
      urinary tract UCs (UUTUCs), and 47 micropapillary, 16 plasmacytoid, 22 small cell
      carcinoma, and 41 sarcomatoid UC variants. RESULTS: UPII expression was
      significantly higher than UPIII expression in conventional BUC (44% vs 17%, P <
      .001) and UUTUC (67% vs 46%, P = .045). UPIII expression was significantly higher
      in UUTUC than in BUC (P < .001). In UC variants, UPII expression was
      significantly higher than UPIII expression in micropapillary (91% vs 25%, P <
      .001), plasmacytoid (63% vs 6%, P < .001), and sarcomatoid (29% vs 5%, P = .032)
      variants. Only rare cases of the small cell carcinoma variant had focal UPII and
      UPIII expression. Compared with conventional UC, the sarcomatoid variant had
      significantly lower UPII expression, whereas the micropapillary variant had
      significantly higher UPII expression (P < .001). CONCLUSIONS: UPII demonstrates a
      significantly higher sensitivity than UPIII in conventional and variant UCs.
      Thus, UPII is a more valuable marker than UPIII in immunohistochemical analyses
      for confirming the urothelial origin of carcinomas.

PMID- 25389342
TI  - Analysis of preanalytical nonconformance in a medium-sized private pathology
      laboratory.
AB  - OBJECTIVES: To determine the frequency of preanalytical nonconformance in a
      medium-sized private pathology laboratory. METHODS: A retrospective audit was
      performed at Southern IML Pathology in Wollongong and Nowra, Australia, to
      identify incidences of nonconformance over a 12-month period from October 2012 to
      September 2013. Data were obtained using an in-house nonconformance reporting
      system and from the quarterly Royal College of Pathologists of Australasia Key
      Incident Monitoring and Management System. RESULTS: There were 584,012 patient
      episodes tested and 2,726,597 tests performed at Southern IML Pathology during
      the study period. Of the 11,266 incidences of nonconformance during the study
      period, 3,613 (32%) were from collection, 2,164 (19%) were from the specimen
      reception area, and 2,242 (20%) were from data entry. In total, 3,045 (27%)
      incidences required a re-collection. A total of 10,972 patients had an incidence
      of preanalytical nonconformance, which is 1.9% of patients who had tests
      performed during the study period. CONCLUSIONS: This is one of few studies of
      preanalytical nonconformance in a medium-sized private laboratory setting.
      Monitoring nonconformance for a pathology laboratory is essential to determine
      areas where further improvements can be made.

PMID- 25389344
TI  - More accurate ways to measure tumor cellularity.

PMID- 25389345
TI  - Access site complications after peripheral vascular interventions: incidence,
      predictors, and outcomes.
AB  - BACKGROUND: Access site hematomas and pseudoaneurysms are the most frequent
      complications of peripheral vascular intervention (PVI); however, their incidence
      and risk factors remain unclear. METHODS AND RESULTS: We retrospectively analyzed
      data from the multicenter Vascular Quality Initiative on 22 226 patients who
      underwent 27 048 PVI from August 2007 to May 2013. Primary end points included
      incidence and predictors of access site complications (ASCs), length of
      postprocedural hospitalization, discharge status, and 30-day and 1-year
      mortality. ASC complicated 936 procedures (3.5%). Of these, 74.4% were minor
      complications, 9.7% were moderate requiring transfusion, 5.4% were moderate
      requiring thrombin injection, and 10.5% were severe requiring surgery. Predictors
      of ASC were age >75 years, female sex, white race, no prior PVI, nonfemoral
      arterial access site, >6-Fr sheath size, thrombolytics, arterial dissection,
      fluoroscopy time >30 minutes, nonuse of vascular closure device, bedridden
      preoperative ambulatory status, and urgent indication. Mean hospitalization was
      longer after procedures complicated by ASC (1.2+/-1.6 versus 1.9+/-1.9 days;
      range, 0-7 days; P=0.002). Severity of ASC correlated with higher rates of
      discharge to rehabilitation/nursing facilities compared with home discharge.
      Patients with severe ASC had higher 30-day mortality (6.1% versus 1.4%; P<0.001),
      and those with moderate ASC requiring transfusion had elevated 1-year mortality
      (12.1% versus 5.7%; P<0.001). CONCLUSIONS: Several factors independently predict
      ASC after PVI. Appropriate use of antithrombotic therapies and vascular closure
      device in patients at increased risk of ASC may improve post-PVI outcomes.

PMID- 25389346
TI  - Pericardial endoscopy-guided left atrial appendage ligation: a pilot study in a
      canine model.
AB  - BACKGROUND: Approaches for closing the left atrial appendage (LAA) have been
      developed for stroke prevention. However, the prevailing maneuvers require an
      open-chest surgery, intravascular access, or transseptal puncture. We evaluated
      the feasibility and safety of pericardial endoscopy-guided LAA ligation in a
      canine model. METHODS AND RESULTS: We used a total of 8 canines and computed
      tomography was performed before the procedures. After a double percutaneous
      pericardiocentesis, a transurethral rigid endoscope was inserted into the
      pericardial space. The ENDOLOOP ligature was advanced to the ostium of the LAA by
      counter pulling the tip of the LAA with forceps. After confirming the positioning
      guided by transesophageal echocardiography, the ligature was securely tightened.
      Acute success was evaluated by transesophageal echocardiography and chronic
      success was evaluated by blood testing, computed tomography, and transesophageal
      echocardiography. The LAA ligation was safely achieved in all canines without
      major complications. One month after the ligation, the ligated LAA was replaced
      by fibrotic tissue, and both the transesophageal echocardiography and computed
      tomographic images revealed no residual shunt. There was only a localized
      adhesion of the pericardium, where the original LAA was located, without the need
      for antibiotic or steroid administration. The postprocedural internal surface of
      the ligated LAA was smooth by virtue of intimal growth. Blood tests showed a
      slight elevation of the inflammatory markers, but this normalized spontaneously.
      CONCLUSIONS: Pericardial endoscopy-guided LAA ligation could provide an
      alternative, minimally invasive, and feasible solution for LAA closure that does
      not require vascular access or a transseptal puncture.

PMID- 25389347
TI  - Pediatric advance care planning from the perspective of health care
      professionals: a qualitative interview study.
AB  - BACKGROUND: Pediatric advance care planning differs from the adult setting in
      several aspects, including patients' diagnoses, minor age, and questionable
      capacity to consent. So far, research has largely neglected the professionals'
      perspective. AIM: We aimed to investigate the attitudes and needs of health care
      professionals with regard to pediatric advance care planning. DESIGN: This is a
      qualitative interview study with experts in pediatric end-of-life care. A
      qualitative content analysis was performed. SETTING/PARTICIPANTS: We conducted 17
      semi-structured interviews with health care professionals caring for severely ill
      children/adolescents, from different professions, care settings, and
      institutions. RESULTS: Perceived problems with pediatric advance care planning
      relate to professionals' discomfort and uncertainty regarding end-of-life
      decisions and advance directives. Conflicts may arise between physicians and non
      medical care providers because both avoid taking responsibility for treatment
      limitations according to a minor's advance directive. Nevertheless, pediatric
      advance care planning is perceived as helpful by providing an action plan for
      everyone and ensuring that patient/parent wishes are respected. Important
      requirements for pediatric advance care planning were identified as follows:
      repeated discussions and shared decision-making with the family, a qualified
      facilitator who ensures continuity throughout the whole process, multi
      professional conferences, as well as professional education on advance care
      planning. CONCLUSION: Despite a perceived need for pediatric advance care
      planning, several barriers to its implementation were identified. The results
      remain to be verified in a larger cohort of health care professionals. Future
      research should focus on developing and testing strategies for overcoming the
      existing barriers.

PMID- 25389348
TI  - Using a three-dimensional model of the Ankle-Foot Orthosis/leg to explore the
      effects of combinations of axis misalignments.
AB  - BACKGROUND AND AIM: Misaligning the mechanical axes of Ankle-Foot Orthoses with
      the ankle axis may lead to tissue damage, reduced gait efficiency, and mechanical
      wear on the orthosis. Previous models developed to describe the consequences of
      joint misalignments have only been applied to the sagittal plane. In this study,
      a previously developed three-dimensional model of the Ankle-Foot Orthosis/leg
      system was used to determine the effects of misalignments in the frontal and
      transverse planes and how they interact with misalignments in the sagittal plane.
      TECHNIQUE: The motion of two corresponding points on the leg and Ankle-Foot
      Orthosis was calculated for different binary combinations of translational and
      rotational misalignments of the mechanical axis, and the resulting displacements
      between those points recorded. DISCUSSION: Misaligning the mechanical joint axis
      of the Ankle-Foot Orthosis in the transverse plane led to much greater
      displacements than other misalignments. Results from the model suggest the
      importance of prioritizing transverse plane alignment by appropriately accounting
      for tibial rotation. CLINICAL RELEVANCE: Misalignments in the transverse plane
      had a dominating effect on relative motion between the Ankle-Foot Orthosis and
      leg emphasizing the importance of including the third dimension in the model and
      prioritizing accuracy of alignment in the transverse plane.

PMID- 25389349
TI  - Implementation of Bubble CPAP in a Rural Ugandan Neonatal ICU.
AB  - BACKGROUND: Respiratory distress is a leading cause of neonatal death in low
      income and middle-income countries. CPAP is a simple and effective respiratory
      support modality used to support neonates with respiratory failure and can be
      used in low-income and middle-income countries. The goal of this study was to
      describe implementation of the Silverman-Andersen respiratory severity score
      (RSS) and bubble CPAP in a rural Ugandan neonatal NICU. We sought to determine
      whether physicians and nurses in a low-income/middle-income setting would assign
      similar RSS in neonates after an initial training period and over time. METHODS:
      We describe the process of training NICU staff to use the RSS to assist in
      decision making regarding initiation, titration, and termination of bubble CPAP
      for neonates with respiratory distress. Characteristics of all neonates with
      respiratory failure treated with bubble CPAP in a rural Ugandan NICU from January
      to June 2012 are provided. RESULTS: Nineteen NICU staff members (4 doctors and 15
      nurses) received RSS training. After this, the Spearman correlation coefficient
      for respiratory severity scoring between doctor and nurse was 0.73. Twenty-one
      infants, all < 3 d of age, were treated with CPAP, with 17 infants starting on
      the day of birth. The majority of infants (16/21, 76%) were preterm, 10 (48%)
      were <1,500 g (birthweight), and 13 (62%) were outborn. The most common diagnoses
      were respiratory distress syndrome (16/21, 76%) and birth asphyxia (5/21, 24%).
      The average RSS was 7.4 +/- 1.3 before starting CPAP, 5.2 +/- 2.3 after 2-4 h of
      CPAP, 4.9 +/- 2.7 after 12-24 h of CPAP, and 3.5 +/- 1.9 before CPAP was
      discontinued. Duration of treatment with CPAP averaged 79 +/- 43 h. Approximately
      half (11/21, 52%) of infants treated with CPAP survived to discharge.
      CONCLUSIONS: Implementing bubble CPAP in a low-income/middle-income setting is
      feasible. The RSS may be a simple and useful tool for monitoring a neonate's
      respiratory status and for guiding CPAP management.

PMID- 25389350
TI  - Idiopathic pulmonary fibrosis with emphysema: evidence of synergy among emphysema
      and idiopathic pulmonary fibrosis in smokers.
AB  - BACKGROUND: Emphysema and fibrosis, typically the idiopathic pulmonary fibrosis
      (IPF) form of usual interstitial pneumonia (UIP), can co-exist as combined
      pulmonary fibrosis emphysema (CPFE). It is unknown whether there is a
      pathobiologic basis for CPFE beyond the coexistence of fibrosis and emphysema.
      The aim of this study was to ascertain radiologic differences in severity of
      fibrosis and emphysema in smokers with IPF versus other forms of UIP. METHODS:
      Computed tomography thorax images were prospectively rescored in retrospectively
      identified smokers (minimum 5-pack-year history) with radiologic UIP (any
      etiology). Radiologic severity (emphysema/fibrosis/reticulation) was scored in
      consensus by two radiologists, blinded to clinical details, across 5 lung
      regional levels, and then correlated with clinical data. RESULTS: For the whole
      cohort (IPF, n=102; non-IPF UIP [mainly rheumatoid
      arthritis/asbestosis/scleroderma], n=30), IPF and non-IPF UIP smokers were
      similar regarding pack-year, age, gender, and lung function (P>.1). IPF smokers
      had greater whole lung fibrosis and reticulation scores (P<.04 in all cases).
      CPFE was present in n=61 (IPF, n=49; non-IPF UIP, n=12). Compared with smokers
      with non-IPF CPFE, smokers with IPF and emphysema (IPFE) were similar regarding
      confounders (P>.1). There were significantly greater regional reticulation
      severity (P=.009), cumulative emphysema severity (P=.04), and cumulative
      reticulation severity (P<.001) scores in IPFE versus non-IPF CPFE. CONCLUSIONS:
      When controlled for confounders, smokers with IPFE have worse radiologic CPFE
      than other smokers with non-IPF UIP and emphysema, suggesting an interactive
      synergy among IPF, emphysema, and smoking, with more extensive emphysema due to
      either inherent susceptibility and/or traction effects. IPFE should be considered
      separately from other CPFE in future work. It is currently unknown whether CPFE
      is a distinct pathobiologic entity; therefore, we identified subjects with
      radiologic UIP (any etiology) who had been similarly exposed to smoke, and asked
      whether there are differences in the extent/severity of radiologic fibrosis
      and/or emphysema in those with IPF versus individuals with non-IPF UIP. Although
      relevant confounders were similar, IPF smokers had greater whole lung fibrosis
      and reticulation scores than smokers with secondary forms of UIP, and in the CPFE
      subgroup, smokers with IPF/emphysema had worse radiologic CPFE findings than
      smokers with non-IPF UIP/emphysema. It is shown for the first time that relevant
      confounding variables do not explain the observed excess radiologic severity of
      emphysema and fibrosis in smokers with IPF compared with smokers with non-IPF
      UIP, lending support to the hypothesis that there is a pathobiologic mechanism or
      synergy involved in IPF with emphysema that is distinct from the mere co
      existence of UIP and emphysematous processes.

PMID- 25389351
TI  - Nitric oxide delivery by neonatal noninvasive respiratory support devices.
AB  - BACKGROUND: Inhaled nitric oxide (INO) has been used with heated and humidified
      high-flow nasal cannula (HFNC), nasal CPAP and several forms of noninvasive
      ventilation (NIV). This study was designed to evaluate the delivered dose of INO,
      level of NO2 generation, and effect of net gas delivery (addition of INO to the
      ventilator circuit--gas removed for sampling) on lung pressure at different NO
      doses during noninvasive respiratory support. METHODS: An infant lung model was
      supported with the different noninvasive modes during INO therapy. NO and NO2
      were measured from within the patient circuit of the noninvasive devices and
      simulated neonatal trachea at several NO levels. Lung pressures were compared
      with and without INO and at several INO settings. RESULTS: Accuracy of NO
      delivery was determined to be within the stated accuracy by the manufacturer with
      nasal CPAP and NIV, but accuracy was compromised during HFNC. INO and NO2
      measured by the INOmax DSIR (Ikaria, Hampton, New Jersey) did not consistently
      reflect the delivered dose of NO or formation of NO2 across all types of neonatal
      noninvasive respiratory support. Tracheal NO2 levels were <1.5 ppm with all forms
      of noninvasive support, except nasal intermittent mandatory ventilation at 40 ppm
      INO. Lung model mean airway pressures were mildly affected by gas
      sampling/delivery during combined INO therapy/HFNC at certain flows but remained
      stable with all other forms of noninvasive support. CONCLUSIONS: Clinicians
      cannot always assume that the set INO level results in a similar lung dose when
      using all forms of neonatal noninvasive support. Clinical decisions regarding
      ways to improve INO delivery may need to include changing settings or placing
      patients on a different form of noninvasive support. The NO2 level delivered to
      the patient could be greater than the value recorded by the INO delivery system.

PMID- 25389352
TI  - Nasal Mucociliary Clearance in Subjects With COPD After Smoking Cessation.
AB  - BACKGROUND: Exposure to cigarette smoke causes significant impairment in
      mucociliary clearance (MCC), which predisposes patients to secretion retention
      and recurrent airway infections that play a role in exacerbations of COPD. To
      determine whether smoking cessation may influence MCC and frequency of
      exacerbations, the following groups were evaluated: ex-smokers with COPD, smokers
      with COPD, current smokers with normal lung function, and nonsmokers with normal
      lung function. METHODS: Ninety-three subjects were divided into 4 groups: ex
      smokers with COPD (n = 23, 62.4 +/- 8.0 y, 13 males), smokers with COPD (n = 17,
      58.2 +/- 8.0 y, 6 males), current smokers (n = 27, 61.5 +/- 6.4 y, 17 males), and
      nonsmokers (n = 26, 60.8 +/- 11.3 y, 7 males). MCC was evaluated using the
      saccharin transit time (STT) test, and the frequency of exacerbations in the last
      year was assessed by questionnaire. The Kruskal-Wallis test followed by Dunn's
      test were used to compare STT among groups, and the Goodman test was used to
      compare the frequency of exacerbations. RESULTS: STT of smokers with COPD (16.5
      [11-28] min; median [interquartile range 25-75%]) and current smokers (15.9 [10
      27] min) was longer compared with ex-smokers with COPD (9.7 [6-12] min) and
      nonsmokers (8 [6-16] min) (P < .001). There was no difference in STT values
      between smokers with COPD and current smokers, and these values in ex-smokers
      with COPD were similar to the control group (P > .05). The frequency of
      exacerbations was lower in ex-smokers with COPD compared with smokers with COPD.
      CONCLUSIONS: One year after smoking cessation, subjects with COPD had improved
      mucociliary clearance.

PMID- 25389353
TI  - Cardiorespiratory interactions: the relationship between mechanical ventilation
      and hemodynamics.
AB  - The overall goal of the cardiorespiratory system is to provide the organs and
      tissues of the body with an adequate supply of oxygen in relation to oxygen
      consumption. An understanding of the complex physiologic interactions between the
      respiratory and cardiac systems is essential to optimal patient management.
      Alterations in intrathoracic pressure are transmitted to the heart and lungs and
      can dramatically alter cardiovascular performance, with significant differences
      existing between the physiologic response of the right and left ventricles to
      changes in intrathoracic pressure. In terms of cardiorespiratory interactions,
      the clinician should titrate the mean airway pressure to optimize the balance
      between mean lung volume (ie, arterial oxygenation) and ventricular function (ie,
      global cardiac output), minimize pulmonary vascular resistance, and routinely
      monitor cardiorespiratory parameters closely. Oxygen delivery to all organs and
      tissues of the body should be optimized, but not necessarily maximized. The heart
      and lungs are, obviously, connected anatomically but also physiologically in a
      complex relationship. 

PMID- 25389354
TI  - Hyperoxemia in mechanically ventilated, critically ill subjects: incidence and
      related factors.
AB  - BACKGROUND: Excessive supplemental oxygen causes injurious hyperoxemia. Before
      establishing the best P(aO2) targets for mechanically ventilated patients, it is
      important to understand the incidence of hyperoxemia and related factors. We
      investigated oxygenation in mechanically ventilated subjects in our ICU and
      evaluated factors related to hyperoxemia (P(aO2) > 120 mm Hg) at 48 h after
      initiation of mechanical ventilation. METHODS: We retrospectively reviewed the
      medical records of patients admitted to our ICU from January 2010 to May 2013.
      Inclusion criteria were 15 y of age or older and administration of mechanical
      ventilation for > 48 h. Patients at risk of imminent death on admission or who
      had received noninvasive ventilation were excluded. We collected subject
      demographics, reasons for mechanical ventilation, and during mechanical
      ventilation, we collected arterial blood gas data and ventilator settings on the
      first day of intubation (T1), 48 h after initiation of mechanical ventilation
      (T2), and on the day of extubation (T3). Multivariable logistic regression
      analysis was performed to clarify independent variables related to hyperoxemia at
      T2. RESULTS: For the study period, data for 328 subjects were analyzed. P(aO2)
      statistically significantly increased over time to 90 (interquartile range of 74
      109) mm Hg at T1, 105 (89-120) mm Hg at T2, and 103 (91-119) mm Hg at T3 (P <
      .001), coincident with decreases in F(IO2) of 0.4 (0.3-0.5) at T1, 0.3 (0.3-0.4)
      at T2, and 0.3 (0.3-0.35) at T3 (P < .001). Hyperoxemia occurred in 15.6% (T1),
      25.3% (T2), and 22.4% (T3) of subjects. Multivariable logistic regression
      analysis revealed that hyperoxemia was independently associated with age of < 40
      y (odds ratio 2.6, 95% CI 1.1-6.0), Acute Physiology and Chronic Health
      Evaluation II scores of >= 30 (odds ratio 0.53, 95% CI 0.3-1.0), and
      decompensated heart failure (odds ratio 1.9, 95% CI 1.1 to 3.5). CONCLUSIONS:
      During mechanical ventilation of critically ill subjects, P(aO2) increased, and
      F(IO2) decreased. One in 4 subjects were hyperoxemic at T2, and hyperoxemia
      persisted until T3.

PMID- 25389355
TI  - The efficacy and safety of subcutaneous immunotherapy in mite-sensitized subjects
      with asthma: a meta-analysis.
AB  - BACKGROUND: Subcutaneous immunotherapy (SCIT) is widely used in the management of
      allergic diseases such as allergic asthma. We aimed to conduct a systematic
      review and meta-analysis to evaluate the efficacy and safety of SCIT in mite
      sensitized subjects with asthma. METHODS: Literature from January 1990 to
      February 2013 on the efficacy and safety of SCIT for mite-sensitized asthma
      patients was searched in electronic databases, including the Cochrane Library,
      MEDLINE, Embase, PubMed, China Knowledge Resource Integrated Database, Wanfang,
      and Vendor Information Pages. Data were extracted from randomized controlled
      trials (RCTs) according to the selection criteria by 2 investigators
      independently. The quality of included trials was evaluated according to the
      Jadad scale standard. RESULTS: A total of 796 subjects from 19 different RCTs
      were included in this analysis. SCIT significantly reduced the asthma symptom
      scores (standardized mean difference of -0.94, 95% CI -1.58 to -0.29, P=.004) and
      the asthma medication scores (standardized mean difference of -1.06, 95% CI -1.70
      to -0.42, P=.001) compared with the control group. However, there were no
      significant differences between subjects receiving SCIT and the control group in
      lung function (peak expiratory flow, percent-of-predicted FEV1, percent-of
      predicted FVC) and specific antibody (allergen-specific immunoglobulin E) levels
      of blood serum (P>.05). In the studies containing data on safety, the incidences
      of systemic and local adverse reactions were 9.1% (8/88) and 17.2% (23/134),
      respectively, in subjects treated with SCIT, and no severe adverse events were
      reported. CONCLUSIONS: Our results suggest that SCIT is helpful in alleviating
      symptoms and reducing medication used in mite-sensitive asthma subjects, but with
      no improvement in lung function. The safety of SCIT is acceptable.

PMID- 25389356
TI  - Single-breath diffusing capacity for carbon monoxide instrument accuracy across 3
      health systems.
AB  - BACKGROUND: Measuring diffusing capacity of the lung for carbon monoxide (DLCO)
      is complex and associated with wide intra- and inter-laboratory variability.
      Increased D(LCO) variability may have important clinical consequences. The
      objective of the study was to assess instrument performance across hospital
      pulmonary function testing laboratories using a D(LCO) simulator that produces
      precise and repeatable D(LCO) values. METHODS: D(LCO) instruments were tested
      with CO gas concentrations representing medium and high range D(LCO) values. The
      absolute difference between observed and target D(LCO) value was used to
      determine measurement accuracy; accuracy was defined as an average deviation from
      the target value of < 2.0 mL/min/mm Hg. Accuracy of inspired volume measurement
      and gas sensors were also determined. RESULTS: Twenty-three instruments were
      tested across 3 healthcare systems. The mean absolute deviation from the target
      value was 1.80 mL/min/mm Hg (range 0.24-4.23) with 10 of 23 instruments (43%)
      being inaccurate. High volume laboratories performed better than low volume
      laboratories, although the difference was not significant. There was no
      significant difference among the instruments by manufacturers. Inspired volume
      was not accurate in 48% of devices; mean absolute deviation from target value was
      3.7%. Instrument gas analyzers performed adequately in all instruments.
      CONCLUSIONS: D(LCO) instrument accuracy was unacceptable in 43% of devices.
      Instrument inaccuracy can be primarily attributed to errors in inspired volume
      measurement and not gas analyzer performance. D(LCO) instrument performance may
      be improved by regular testing with a simulator. Caution should be used when
      comparing D(LCO) results reported from different laboratories.

PMID- 25389357
TI  - Neonatal respiratory therapist-led rounds can improve staff satisfaction and
      timeliness of respiratory interventions.
AB  - BACKGROUND: Interdisciplinary rounding is used to establish and communicate
      patient care goals and monitor progress toward goal attainment. This study
      describes staff satisfaction and process outcomes associated with respiratory
      therapist (RT)-led interdisciplinary rounds in the neonatal ICU. We hypothesized
      improved staff satisfaction, execution of orders within 30 min of order entry
      into the electronic medical record, and communication of accurate and complete
      data during rounds to the interdisciplinary team. METHODS: Nurses, RTs, nurse
      practitioners, residents, and attending physicians completed the 13-question
      survey eliciting demographic information and evaluating staff engagement and
      professional satisfaction. The survey was anonymous and confidential, and
      informed consent was implied. Process data were collected for a 10-d period at 2
      intervals through direct observation of the rounding process and electronic
      medical record review. Descriptive statistics reported patient demographics,
      responses to job satisfaction and engagement survey questions, the number of
      patients who were visited in daily rounds, the number and type of orders given
      during rounds, and the number of respiratory orders that were addressed in
      multidisciplinary teaching rounds rather than during respiratory rounds. The chi
      square test was used to determine differences in the proportion of inaccurate and
      incomplete data communicated during rounds between the 2 data collection periods.
      The Mann-Whitney U test was used to determine differences in the timeliness of
      electronic medical record order entry and time to order completion. RESULTS: A
      94.8% survey response rate (n = 55) was obtained. Seventy-six percent of
      participants reported improved communication. Sixty-nine percent of participants
      reported improved teamwork. Eighty-six percent of orders were implemented
      immediately after electronic medical record entry. Correct information was
      provided on 95% and 99.3% of patients (P < .066) and complete information on 93%
      and 96% of patients (P = .41). CONCLUSIONS: Implementation of respiratory rounds
      improved staff satisfaction and the timeliness of completing respiratory orders.
      Spot monitoring at intermittent intervals verified process sustainability.

PMID- 25389360
TI  - Indoor radon measurements in Turkey dwellings.
AB  - In this work, indoor radon radioactivity concentration levels have been measured
      in dwellings of Turkey within the frame of the National Radon Monitoring
      Programme. The (222)Rn concentrations were measured with time-integrating passive
      nuclear etched track detectors in 7293 dwellings in 153 residential units of 81
      provinces, and the radon map of Turkey was prepared. Indoor radon concentrations
      were distributed in the range of 1-1400 Bq m(-3). The arithmetic mean of the
      radon gas concentration was found to be 81 Bq m(-3); the geometric mean was 57 Bq
      m(-3) with a geometric standard deviation of 2.3.

PMID- 25389361
TI  - Units related to radiation exposure and radioactivity in mass media: the
      Fukushima case study in Europe and Russia.
AB  - Using an analysis of the way European newspapers covered the Fukushima nuclear
      accident, this article explores how the mass media transmit information about
      radiation risks from experts to the general public. The study applied a media
      content analysis method on a total of 1340 articles from 12 leading newspapers in
      6 countries: Belgium (N = 260), Italy (N = 270), Norway (N = 133), Russia (N =
      172), Slovenia (N = 190) and Spain (N = 315). All articles analysed were selected
      as being directly or indirectly related to the Fukushima accident by containing
      the word 'nuclear' and/or 'Fukushima' and were published between the 11th March
      and the 11th May 2011. The data presented here focus specifically on a cross
      cultural comparison of the way the media use quantitative units. Results suggest
      that although experts are accustomed to communicating about radiological risks in
      technical language, often using quantitative units to describe the risks, mass
      media do not tend to use these units in their reporting. Although the study found
      a large variation in the measurement units used in different countries, it
      appeared that journalists in all the analysed countries preferred to describe
      radioactivity by comparing different radiation exposures, rather than reporting
      the actual measured units. The paper concludes with some practical guidelines for
      sound public communication about radiation risks. 

PMID- 25389358
TI  - Selective glucocorticoid receptor modulator compound A, in contrast to
      prednisolone, does not induce leptin or the leptin receptor in human
      osteoarthritis synovial fibroblasts.
AB  - OBJECTIVE: Glucocorticoids are powerful anti-inflammatory compounds that also
      induce the expression of leptin and leptin receptor (Ob-R) in synovial
      fibroblasts through TGF-betasignalling and Smad1/5 phosphorylation. Compound A
      (CpdA), a selective glucocorticoid receptor agonist, reduces inflammation in
      murine arthritis models and does not induce diabetes or osteoporosis, thus
      offering an improved risk:benefit ratio in comparison with glucocorticoids. Due
      to the detrimental role of leptin in OA pathogenesis, we sought to determine
      whether CpdA also induced leptin and Ob-R protein expression as observed with
      prednisolone. METHODS: Human synovial fibroblasts and chondrocytes were isolated
      from the synovium and cartilage of OA patients after joint surgery. The cells
      were treated with prednisolone, TGF-beta1, TNF-alpha and/or CpdA. Levels of
      leptin, IL-6, IL-8, MMP-1 and MMP-3 were measured by ELISA and expression levels
      of Ob-R phospho-Smad1/5, phospho-Smad2, alpha-tubulin and glyceraldehyde 3
      phosphate dehydrogenase were analysed by western blotting. RESULTS: CpdA, unlike
      prednisolone, did not induce leptin secretion or Ob-R protein expression in OA
      synovial fibroblasts. Moreover, CpdA decreased endogenous Ob-R expression and
      down-regulated prednisolone-induced leptin secretion and Ob-R expression.
      Mechanistically, CpdA, unlike prednisolone, did not induce Smad1/5
      phosphorylation. CpdA, similarly to prednisolone, down-regulated endogenous and
      TNF-alpha-induced IL-6, IL-8, MMP-1 and MMP-3 protein secretion. The dissociative
      effect of CpdA was confirmed using chondrocytes with no induction of leptin
      secretion, but with a significant decrease in IL-6, IL-8, MMP-1 and MMP-3 protein
      secretion. CONCLUSION: CpdA, unlike prednisolone, did not induce leptin or Ob-R
      in human OA synovial fibroblasts, thereby demonstrating an improved risk:benefit
      ratio.

PMID- 25389362
TI  - Evaluation of the CT dose index for scans with an ECG using a 320-row multiple
      detector CT scanner.
AB  - The relationship between heart rate (HR) and computed tomography dose index
      (CTDI) was evaluated using an electrocardiogram (ECG) gate scan for scan
      applications such as prospective triggering, Ca scoring, target computed
      tomography angiography (CTA), prospective CTA and retrospective gating,
      continuous CTA/CFA (cardiac functional analysis) and CTA/CFA modulation. Even in
      the case of a volume scan, doses for the multiple scan average dose were similar
      to those for CTDI. Moreover, it was found that the ECG gate scan yields
      significantly different doses. When selecting the optimum scan, the doses were
      dependent on many factors such as HR, scan rotation time, active time,
      prespecified cardiac phase and modulation rate. Therefore, it is necessary to
      take these results into consideration when selecting the scanning parameters.

PMID- 25389363
TI  - CYP2J2 attenuates metabolic dysfunction in diabetic mice by reducing hepatic
      inflammation via the PPARgamma.
AB  - Epoxyeicosatrienoic acids (EETs) and arachidonic acid-derived cytochrome P450
      (CYP) epoxygenase metabolites have diverse biological effects, including anti
      inflammatory properties in the vasculature. Increasing evidence suggests that
      inflammation in type 2 diabetes is a key component in the development of insulin
      resistance. In this study, we investigated whether CYP epoxygenase expression and
      exogenous EETs can attenuate insulin resistance in diabetic db/db mice and in
      cultured hepatic cells (HepG2). In vivo, CYP2J2 expression and the accompanying
      increase in EETs attenuated insulin resistance, as determined by plasma glucose
      levels, glucose tolerance test, insulin tolerance test, and hyperinsulinemic
      euglycemic clamp studies. CYP2J2 expression reduced the production of
      proinflammatory cytokines in liver, including CRP, IL-6, IL-1beta, and TNFalpha,
      and decreased the infiltration of macrophages in liver. CYP2J2 expression also
      decreased activation of proinflammatory signaling cascades by decreasing NF
      kappaB and MAPK activation in hepatocytes. Interestingly, CYP2J2 expression and
      exogenous EET treatment increased glucose uptake and activated the insulin
      signaling cascade both in vivo and in vitro, suggesting that CYP2J2 metabolites
      play a role in glucose homeostasis. Furthermore, CYP2J2 expression upregulated
      PPARgamma, which has been shown to induce adipogenesis, which attenuates
      dyslipidemias observed in diabetes. All of the findings suggest that CYP2J2
      expression attenuates the diabetic phenotype and insulin resistance via
      inhibition of NF-kappaB and MAPK signaling pathways and activation of PPARgamma. 

PMID- 25389364
TI  - 11beta-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid
      induced insulin resistance and lipolysis in mouse abdominal adipose tissue.
AB  - Long-term glucocorticoid exposure increases the risk for developing type 2
      diabetes. Prereceptor activation of glucocorticoid availability in target tissue
      by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) coupled with hexose-6
      phosphate dehydrogenase (H6PDH) is an important mediator of the metabolic
      syndrome. We explored whether the tissue-specific modulation of 11beta-HSD1 and
      H6PDH in adipose tissue mediates glucocorticoid-induced insulin resistance and
      lipolysis and analyzed the effects of 11beta-HSD1 inhibition on the key lipid
      metabolism genes and insulin-signaling cascade. We observed that corticosterone
      (CORT) treatment increased expression of 11beta-HSD1 and H6PDH and induced lipase
      HSL and ATGL with suppression of p-Thr(172) AMPK in adipose tissue of C57BL/6J
      mice. In contrast, CORT induced adipose insulin resistance, as reflected by a
      marked decrease in IR and IRS-1 gene expression with a reduction in p-Thr(308)
      Akt/PKB. Furthermore, 11beta-HSD1 shRNA attenuated CORT-induced 11beta-HSD1 and
      lipase expression and improved insulin sensitivity with a concomitant stimulation
      of pThr(308) Akt/PKB and p-Thr(172) AMPK within adipose tissue. Addition of CORT
      to 3T3-L1 adipocytes enhanced 11beta-HSD1 and H6PDH and impaired p-Thr(308)
      Akt/PKB, leading to lipolysis. Knockdown of 11beta-HSD1 by shRNA attenuated CORT
      induced lipolysis and reversed CORT-mediated inhibition of pThr(172) AMPK, which
      was accompanied by a parallel improvement of insulin signaling response in these
      cells. These findings suggest that elevated adipose 11beta-HSD1 expression may
      contribute to glucocorticoid-induced insulin resistance and adipolysis. 

PMID- 25389365
TI  - Liver growth factor induces testicular regeneration in EDS-treated rats and
      increases protein levels of class B scavenger receptors.
AB  - The aim of the present work was to determine the effects of liver growth factor
      (LGF) on the regeneration process of rat testes after chemical castration induced
      by ethane dimethanesulfonate (EDS) by analyzing some of the most relevant
      proteins involved in cholesterol metabolism, such as hormone sensitive lipase
      (HSL), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), scavenger receptor SR-BI,
      and other components of the SR family that could contribute to the recovery of
      steroidogenesis and spermatogenesis in the testis. Sixty male rats were
      randomized to nontreated (controls) and LGF-treated, EDS-treated, and EDS + LGF
      treated groups. Testes were obtained on days 10 (T1), 21 (T2), and 35 (T3) after
      EDS treatment, embedded in paraffin, and analyzed by immunohistochemistry and
      Western blot. LGF improved the recovery of the seminiferous epithelia, the
      appearance of the mature pattern of Leydig cell interstitial distribution, and
      the expression of mature SR-BI. Moreover, LGF treatment resulted in partial
      recovery of HSL expression in Leydig cells and spermatogonia. No changes in serum
      testosterone were observed in control or LGF-treated rats, but in EDS-castrated
      animals LGF treatment induced a progressive increase in serum testosterone levels
      and 3beta-HSD expression. Based on the pivotal role of SR-BI in the uptake of
      cholesteryl esters from HDL, it is suggested that the observed effects of LGF
      would facilitate the provision of cholesterol for sperm cell growth and Leydig
      cell recovery.

PMID- 25389367
TI  - Partnering in research: a national research trial exemplifying effective
      collaboration with American Indian Nations and the Indian Health Service.
AB  - Despite the fact that numerous major public health problems have plagued American
      Indian communities for generations, American Indian participation in health
      research traditionally has been sporadic in many parts of the United States. In
      2002, the University of Oklahoma Health Sciences Center (Oklahoma City, Oklahoma)
      and 5 Oklahoma American Indian research review boards (Oklahoma City Area Indian
      Health Service, Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, and
      Choctaw Nation) agreed to participate collectively in a national research trial,
      the Treatment Options for Type 2 Diabetes in Adolescence and Youth (TODAY) Study.
      During that process, numerous lessons were learned and processes developed that
      strengthened the partnerships and facilitated the research. Formal Memoranda of
      Agreement addressed issues related to community collaboration, venue, tribal
      authority, preferential hiring of American Indians, and indemnification. The
      agreements aided in uniting sovereign nations, the Indian Health Service,
      academics, and public health officials to conduct responsible and ethical
      research. For more than 10 years, this unique partnership has functioned
      effectively in recruiting and retaining American Indian participants, respecting
      cultural differences, and maintaining tribal autonomy through prereview of all
      study publications and local institutional review board review of all processes.
      The lessons learned may be of value to investigators conducting future research
      with American Indian communities. 

PMID- 25389366
TI  - CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high
      fat diet in mice.
AB  - Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert
      diverse biological activities, which include potent vasodilatory, anti
      inflammatory, antiapoptotic, and antioxidatant effects, and cardiovascular
      protection. Liver has abundant epoxygenase expression and high levels of EET
      production; however, the roles of epoxygenases in liver diseases remain to be
      elucidated. In this study, we investigated the protection against high-fat diet
      induced nonalcoholic fatty liver disease (NAFLD) in mice with endothelial
      specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 wk of high-fat diet,
      Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared with controls. Tie2
      CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and
      liver lipid accumulation, improved liver function, reduced inflammatory
      responses, and less increase in hepatic oxidative stress than wild-type control
      mice. These effects were associated with inhibition of NF-kappaB/JNK signaling
      pathway activation and enhancement of the antioxidant defense system in Tie2
      CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected
      HepG2 cells against palmitic acid-induced inflammation and oxidative stress.
      14,15-EET attenuated palmitic acid-induced changes in NF-kappaB/JNK signaling
      pathways, malondialdehyde generation, glutathione levels, reactive oxygen species
      production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in
      vitro. Together, these results highlight a new role for CYP epoxygenase-derived
      EETs in lipotoxicity-related inflammation and oxidative stress and reveal a new
      molecular mechanism underlying EETs-mediated anti-inflammatory and antioxidant
      effects that could aid in the design of new therapies for the prevention and
      treatment of NAFLD.

PMID- 25389368
TI  - Graft extrusion in both the coronal and sagittal planes is greater after medial
      compared with lateral meniscus allograft transplantation but is unrelated to
      early clinical outcomes.
AB  - BACKGROUND: Graft extrusion after meniscus allograft transplantation (MAT) may be
      affected by horn fixation, which differs between medial and lateral MAT. Few
      studies have compared graft extrusion, especially sagittal extrusion, after
      medial and lateral MAT. HYPOTHESIS: In patients undergoing medial and lateral
      MAT, graft extrusion is likely similar and not correlated with postoperative
      Lysholm scores. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS:
      Meniscus graft extrusion in the coronal and sagittal planes was compared in 51
      knees undergoing medial MAT and 84 undergoing lateral MAT. Distances from the
      anterior and posterior articular cartilage margins to the anterior (anterior
      cartilage meniscus distance [ACMD]) and posterior (posterior cartilage meniscus
      distance [PCMD]) horns, respectively, were assessed on immediate postoperative
      magnetic resonance imaging and compared in patients undergoing medial and lateral
      MAT. Correlations between coronal and sagittal graft extrusion and between
      extrusion and the Lysholm score were compared in the 2 groups. RESULTS: In the
      coronal plane, mean absolute (4.3 vs 2.7 mm, respectively; P<.001) and relative
      (39% vs 21%, respectively; P<.001) graft extrusions were significantly greater
      for medial than lateral MAT. In the sagittal plane, mean absolute and relative
      ACMD and PCMD values were significantly greater for medial than lateral MAT
      (P<.001 each). For both medial and lateral MAT, mean absolute and relative ACMDs
      were significantly larger than PCMDs (P<.001 each). Graft extrusion>3 mm in the
      coronal plane was significantly more frequent in the medial (78%) than in the
      lateral (35%) MAT group. In the sagittal plane, the frequencies of ACMDs (72% vs
      39%, respectively) and PCMDs (23% vs 4%, respectively) >3 mm were also
      significantly greater in the medial than in the lateral MAT group. Coronal and
      sagittal extrusions were not correlated with postoperative Lysholm scores for
      both medial and lateral MAT. CONCLUSION: The amount and incidence of graft
      extrusion were greater after medial than lateral MAT in both the coronal and
      sagittal planes. In the sagittal plane, graft extrusion was greater and more
      frequent on the anterior than the posterior horn in both medial and lateral MAT.
      However, graft extrusion was not correlated with early clinical outcomes after
      both medial and lateral MAT.

PMID- 25389369
TI  - Intratendinous rotator cuff tears: prevalence and clinical and radiological
      outcomes of arthroscopically confirmed intratendinous tears at midterm follow-up.
AB  - BACKGROUND: Intratendinous tears of the rotator cuff are rare, and little has
      been written about them. PURPOSE: To investigate the prevalence and clinical and
      radiological outcomes of arthroscopically confirmed intratendinous tears treated
      with transtendon suture bridge repair. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Included in the study were 33 patients (16 male, 17 female;
      mean age, 53.4 years) with arthroscopically confirmed intratendinous tears
      treated with transtendon suture bridge repair from March 2006 to July 2012. A
      history of trauma was found in 10 cases (30.3%). The dominant arm was involved in
      26 cases (78.8%). The mean follow-up duration was 56 months. Preoperatively, a
      thorough physical examination was performed; at final follow-up, shoulder range
      of motion (ROM) in forward flexion, abduction, external rotation (ER) at the
      side, and internal rotation (IR) at the back was noted, and clinical outcomes
      (American Shoulder and Elbow Surgeons [ASES] score; University of California, Los
      Angeles [UCLA] score; visual analog scale [VAS] for pain; and Simple Shoulder
      Test [SST]) were recorded and compared with the preoperative data. Postoperative
      magnetic resonance imaging (MRI) was performed at 6 months to investigate rotator
      cuff healing status and repair integrity. RESULTS: The prevalence of
      arthroscopically confirmed intratendinous tears was 4.7% among all
      arthroscopically treated partial-thickness rotator cuff tears. Impingement signs
      were positive in most of the patients (positive Hawkins-Kennedy test result in
      78.8%, positive Neer sign in 66.7%, and either positive Hawkins-Kennedy test
      result or Neer sign in 84.8%). At final follow-up, mean ASES, UCLA, VAS, and SST
      scores improved significantly from a preoperative mean of 51.4, 18.9, 6.0, and
      5.4, respectively, to a postoperative mean of 90.6, 32.9, 1.4, and 10.8,
      respectively (P < .001). According to the UCLA rating scale, outcomes were
      excellent in 17, good in 13, and fair in 3 cases. Shoulder ROM in forward
      flexion, abduction, ER at the side, and IR at the back improved from a
      preoperative mean of 135 degrees , 129 degrees , 25 degrees , and L2,
      respectively, to a postoperative mean of 161 degrees , 160 degrees , 29 degrees ,
      and T10, respectively (P < .001 for all except ER). As per the Sugaya
      classification, on postoperative MRI, type I healing status was found in 10
      (30.3%), type II in 18 (54.5%), and type III in 2 (6.1%) cases. None of the
      patients showed any evidence of retears. CONCLUSION: Transtendon suture bridge
      repair yielded satisfactory clinical and radiological outcomes in patients with
      intratendinous rotator cuff tears.

PMID- 25389370
TI  - Dust, endotoxin, fungi, and bacteria exposure as determined by work task, season,
      and type of plant in a flower greenhouse.
AB  - BACKGROUND: Greenhouse workers are exposed to dust, endotoxin, fungi, and
      bacteria potentially causing airway inflammation as well as systemic symptoms.
      Knowledge about determinants of exposure is a prerequisite for efficient
      prevention through knowledge-based reduction in exposure. The objective of this
      study was to assess the occupational exposure in a flower greenhouse and to
      investigate the impact of work tasks on the intensity and variability in
      exposure. METHODS: Seventy-six personal full-shift exposure measurements were
      performed on 38 employees in a Danish flower greenhouse producing Campanula,
      Lavandula, Rhipsalideae, and Helleborus. The samples were gravimetrically
      analysed for inhalable dust. Endotoxin was assessed by the Limulus Amoebocyte
      Lysate test and culture-based quantification of bacteria and fungi was performed.
      Information on the performed tasks during sampling was extracted from the
      greenhouse electronic task logging system. Associations between log-transformed
      exposure outcomes, season, and work tasks were examined in linear mixed-effects
      regression with worker identity as random effect. RESULTS: Measured
      concentrations ranged between 0.04 and 2.41mg m(-3) for inhalable dust and
      between 0.84 and 1097 EU m(-3) for endotoxin exposure, with the highest mean
      levels measured during Lavandula and Campanula handling, respectively. Personal
      exposure to fungi ranged between 1.8*10(2) and 3.4*10(6) colony-forming units
      (CFU) m(-3) and to bacteria between 1.6*10(1) and 4.2*10(5) CFU m(-3). Exposure
      to dust, endotoxin, fungi, and bacteria differed between seasons. Packing
      Lavandula, sticking, potting, and grading Rhipsalideae, and all examined tasks
      related to Campanula production except sticking increased dust exposure.
      Endotoxin exposure was increased during sticking Campanula and pinching or
      packing Rhipsalideae, and fungi exposure was elevated by subtasks performed in
      the research and development area for Campanula, and by potting, packing/dumping
      Campanula. Sticking and working with subtasks in the research and development
      area for Campanula increased bacteria exposure. CONCLUSION: This study revealed
      moderate dust exposure levels compared to the levels observed in other greenhouse
      productions and other occupations with organic dust exposure such as farming.
      However, high exposures to bacteria and fungi were detected during selected tasks
      and the proposed health-based endotoxin exposure limit of 90 EU m(-3) was
      exceeded in 30% of the samples, which may have health implications for the
      employees. Exposure levels were found to vary depending on the tasks performed,
      and thereby results can be used to direct task-based initiatives to reduce
      workplace exposures.

PMID- 25389372
TI  - Resistance to dual blockade of the kinases PI3K and mTOR in KRAS-mutant
      colorectal cancer models results in combined sensitivity to inhibition of the
      receptor tyrosine kinase EGFR.
AB  - Targeted blockade of aberrantly activated signaling pathways is an attractive
      therapeutic strategy for solid tumors, but drug resistance is common. KRAS is a
      frequently mutated gene in human cancer but remains a challenging clinical
      target. Inhibitors against KRAS signaling mediators, namely, PI3K
      (phosphatidylinositol 3-kinase) and mTOR (mechanistic target of rapamycin), have
      limited clinical efficacy as single agents in KRAS-mutant colorectal cancer
      (CRC). We investigated potential bypass mechanisms to PI3K/mTOR inhibition in
      KRAS-mutant CRC. Using genetically engineered mouse model cells that had acquired
      resistance to the dual PI3K/mTOR small-molecule inhibitor PF-04691502, we
      determined with chemical library screens that inhibitors of the ERBB [epidermal
      growth factor receptor (EGFR)] family restored the sensitivity to PF-04691502.
      Although EGFR inhibitors alone have limited efficacy in reducing KRAS-mutant
      tumors, we found that PF-04691502 induced the abundance, phosphorylation, and
      activity of EGFR, ERBB2, and ERBB3 through activation of FOXO3a (forkhead box O
      3a), a transcription factor inhibited by the PI3K to AKT pathway. PF-04691502
      also induced a stem cell-like gene expression signature. KRAS-mutant patient
      derived xenografts from mice treated with PF-04691502 had a similar gene
      expression signature and exhibited increased EGFR activation, suggesting that
      this drug-induced resistance mechanism may occur in patients. Combination therapy
      with dacomitinib (a pan-ERBB inhibitor) restored sensitivity to PF-04691502 in
      drug-resistant cells in culture and induced tumor regression in drug-resistant
      allografts in mice. Our findings suggest that combining PI3K/mTOR and EGFR
      inhibitors may improve therapeutic outcome in patients with KRAS-mutant CRC. 

PMID- 25389371
TI  - Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1
      to increase acetylation and activation of p53 and p65.
AB  - Inflammation increases the abundance of inducible nitric oxide synthase (iNOS),
      leading to enhanced production of nitric oxide (NO), which can modify proteins by
      S-nitrosylation. Enhanced NO production increases the activities of the
      transcription factors p53 and nuclear factor kappaB (NF-kappaB) in several models
      of disease-associated inflammation. S-nitrosylation inhibits the activity of the
      protein deacetylase SIRT1. SIRT1 limits apoptosis and inflammation by
      deacetylating p53 and p65 (also known as RelA), a subunit of NF-kappaB. We showed
      in multiple cultured mammalian cell lines that NO donors or inflammatory stimuli
      induced S-nitrosylation of SIRT1 within CXXC motifs, which inhibited SIRT1 by
      disrupting its ability to bind zinc. Inhibition of SIRT1 reduced deacetylation
      and promoted activation of p53 and p65, leading to apoptosis and increased
      expression of proinflammatory genes. In rodent models of systemic inflammation,
      Parkinson's disease, or aging-related muscular atrophy, S-nitrosylation of SIRT1
      correlated with increased acetylation of p53 and p65 and activation of p53 and NF
      kappaB target genes, suggesting that S-nitrosylation of SIRT1 may represent a
      proinflammatory switch common to many diseases and aging. 

PMID- 25389374
TI  - The sun compass revisited.
AB  - Many animals, and birds in particular, are thought to use directional information
      from the sun in the form of a time-compensated sun compass, with predictably
      deviated orientation under clock shift being regarded as the litmus test of this.
      We suggest that this paradigm obscures a number of other ways in which solar
      derived information could be important in animal orientation. We distinguish
      between the known use of the sun's azimuth to provide absolute geographical
      direction (compass mechanism) and its possible use to detect changes in heading
      (heading indicator mechanism). Just as in an aircraft, these two kinds of
      information may be provided by separate mechanisms and used for different
      functions, for example for navigation versus steering. We also argue that
      although a solar compass must be time-referenced to account for the sun's
      apparent diurnal movement, this need not entail full time compensation. This is
      because animals might also use time-dependent solar information in an
      associatively acquired, and hence time-limited, way. Furthermore, we show that a
      solar heading indicator, when used on a sufficiently short timescale, need not
      require time compensation at all. Finally, we suggest that solar-derived cues,
      such as shadows, could also be involved in navigation in ways that depend
      explicitly upon position, and are therefore not strictly compass-related. This
      could include giving directionality to landmarks, or acting as time-dependent
      landmarks involved in place recognition. We conclude that clock shift experiments
      alone are neither necessary nor sufficient to identify the occurrence of all
      conceivable uses of solar information in animal orientation, so that a
      predictable response to clock shift should not be regarded as an acid test of the
      use of solar information in navigation.

PMID- 25389373
TI  - Type I interferon signaling contributes to the bias that Toll-like receptor 4
      exhibits for signaling mediated by the adaptor protein TRIF.
AB  - Signaling by Toll-like receptor 4 (TLR4) is mediated by either of two adaptor
      proteins: myeloid differentiation marker 88 (MyD88) or Toll-interleukin-1 (IL-1)
      receptor (TIR) domain-containing adaptor inducing interferon-beta (TRIF). Whereas
      MyD88-mediated signaling leads to proinflammatory responses, TRIF-mediated
      signaling leads to less toxic immunostimulatory responses that are beneficial in
      boosting vaccine responses. The hypothesis that monophosphorylated lipid A
      structures act as TRIF-biased agonists of TLR4 offered a potential mechanism to
      explain their clinical value as vaccine adjuvants, but studies of TRIF-biased
      agonists have been contradictory. In experiments with mouse dendritic cells, we
      found that irrespective of the agonist used, TLR4 functioned as a TRIF-biased
      signaling system through a mechanism that depended on the autocrine and paracrine
      effects of type I interferons. The TLR4 agonist synthetic lipid A induced
      expression of TRIF-dependent genes at lower concentrations than were necessary to
      induce the expression of genes that depend on MyD88-mediated signaling. Blockade
      of type I interferon signaling selectively decreased the potency of lipid A
      (increased the concentration required) in inducing the expression of TRIF
      dependent genes, thereby eliminating adaptor bias. These data may explain how
      high-potency TLR4 agonists can act as clinically useful vaccine adjuvants by
      selectively activating TRIF-dependent signaling events required for
      immunostimulation, without or only weakly activating potentially harmful MyD88
      dependent inflammatory responses. 

PMID- 25389375
TI  - The anuran vocal sac: a tool for multimodal signalling.
AB  - Although in anurans the predominant mode of intra- and intersexual communication
      is vocalization, modalities used in addition to or instead of acoustic signals
      range from seismic and visual to chemical. In some cases, signals of more than
      one modality are produced through or by the anuran vocal sac. However, its role
      beyond acoustics has been neglected for some time and nonacoustic cues such as
      vocal sac movement have traditionally been seen as an epiphenomenon of sound
      production. The diversity in vocal sac coloration and shape found in different
      species is striking and recently its visual properties have been given a more
      important role in signalling. Chemosignals seem to be the dominant communication
      mode in newts, salamanders and caecilians and certainly play a role in the
      aquatic life phase of anurans, but airborne chemical signalling has received less
      attention. There is, however, increasing evidence that at least some terrestrial
      anuran species integrate acoustic, visual and chemical cues in species
      recognition and mate choice and a few secondarily mute anuran species seem to
      fully rely on volatile chemical cues produced in glands on the vocal sac. Within
      vertebrates, frogs in particular are suitable organisms for investigating
      multimodal communication by means of experiments, since they are tolerant of
      disturbance by observers and can be easily manipulated under natural conditions.
      Thus, the anuran vocal sac might be of great interest not only to herpetologists,
      but also to behavioural biologists studying communication systems.

PMID- 25389376
TI  - Hepatocyte growth factor levels in the saliva and gingival crevicular fluid in
      smokers with periodontitis.
AB  - Hepatocyte growth factor (HGF) production by oral fibroblasts is enhanced by
      various molecules that are induced during inflammatory conditions including
      periodontitis. HGF plays an important role in the progression of periodontitis,
      by stimulating intense growth of epithelial cells and preventing regeneration of
      connective tissue attachments. Smokers have a greater risk factor in the
      pathogenesis and progression of periodontal disease. The objective of the study
      was to estimate the level of HGF in saliva and gingival crevicular fluid (GCF) in
      smokers with periodontitis and to compare these levels with that of nonsmokers
      with periodontitis and healthy controls. The HGF levels were found to be
      significantly high in the saliva and GCF of smokers with periodontitis compared
      to both never-smokers with periodontitis and the healthy control group. The
      elevated levels of HGF in the saliva and GCF in the study population could
      explain the intrinsic mechanism triggering the severity of the periodontitis in
      smokers. Further studies are necessary to validate the current observations and
      to establish a sensitive marker to predict periodontal disease activity. 

PMID- 25389377
TI  - Cervical dysplasia and high-risk human papillomavirus infections among HIV
      infected and HIV-uninfected adolescent females in South Africa.
AB  - BACKGROUND: HIV-infected adolescents may be at higher risk for high-grade
      cervical lesions than HIV-uninfected adolescents. The purpose of this study was
      to compare the prevalence of high-risk HPV (HR-HPV) infections and Pap smear
      abnormalities between these two groups. METHODS: In this cross-sectional study,
      we compared the HPV DNA and Pap smear results between 35 HIV-infected and 50 HIV
      uninfected adolescents in order to determine the prevalence of HR-HPV genotypes
      and cervical cytological abnormalities. Comparisons were made using Pearson chi
      (2) and independent-samples t-tests analyses, and associations between
      demographic and behavioral characteristics and HPV infections were examined.
      RESULTS: HIV-infected participants were more likely to be infected with any HPV
      (88.6% versus 48.0%; P < 0.001) and with at least one HR-HPV (60.0% versus 24.0%;
      P = 0.001), and to have multiple concurrent HPV infections (68.6% versus 22.0%; P
      < 0.001). HPV 16 and 18 were relatively underrepresented among HR-HPV infections.
      Abnormal Pap test results were more common among HIV-infected participants (28.8%
      versus 12.0%; P = 0.054). A history of smoking was associated with HR-HPV
      infection. CONCLUSIONS: HIV-infected adolescents have an increased risk of
      infection with HR-HPV and of Pap test abnormalities. The majority of HR-HPV
      infections among our participants would not be prevented by the currently
      available vaccinations against HPV.

PMID- 25389378
TI  - Upregulation of ICAM-1 in diabetic rats after transient forebrain ischemia and
      reperfusion injury.
AB  - BACKGROUND: Hyperglycemia exacerbates brain damage caused by cerebral ischemia.
      Neuroinflammation may play a role in mediating such enhanced damage. The
      objectives of this study were to examine the mRNA and protein levels and cell
      type distribution of ICAM-1 after cerebral ischemia in normo-and diabetic
      hyperglycemic rats. RESULTS: Compared to normoglycemic ischemia animals, diabetes
      aggravated neuronal death, decreased Nissl body staining, and increased ICAM-1
      mRNA and protein levels in the frontal cortex. The increased ICAM-1 was located
      not only in vascular endothelial cells but also in cortical neurons. CONCLUSIONS:
      Our results suggest that exacerbated neuro-inflammation in the brain may mediate
      the detrimental effects of diabetes on the ischemic brain.

PMID- 25389379
TI  - Effects of energy drink major bioactive compounds on the performance of young
      adults in fitness and cognitive tests: a randomized controlled trial.
AB  - BACKGROUND: The consumption of beverages containing caffeine and taurine before
      exercising has been associated with increased physical and psychological
      performances and has been promoted to support the emotional state and provide
      vitality to consumers. However, there are contradictory results on these issues,
      it is not clear the effect of every major compound in relation to the whole
      effect of the beverages and there is a lack in knowledge about their degree of
      safety for consumption. METHODS: This study used a double-blind, placebo
      controlled, randomized, crossover design. Fourteen male volunteer soldiers from
      the Colombian army performed different tests to measure their cardiorespiratory
      fitness (VO2max and maximum heart rate), time to exhaustion, strength (isometric
      strength), power (vertical jump), concentration (Grid test) and memory (Digits
      test) after drinking 250 ml of one of the following beverages: one with 80 mg
      caffeine, one with 1000 mg taurine, one with 80 mg caffeine plus 1000 mg taurine,
      a commercial energy drink (Red Bull(r)) or a placebo drink. Subjects were
      caffeine-consumers that avoided caffeine during the day of evaluation. All
      beverages were matched in flavor and other organoleptic properties to the
      commercial one, were bottled in dark plastic bottles and were administered in
      identical conditions to the participants. Differences between treatments were
      assessed using repeated measures and analysis of variance. RESULTS: The mean +/-
      SD values of VO2max, maximum heart rate, time to exhaustion, right handgrip
      strength, left handgrip strength, vertical jump, Grid test and Digits test were
      61.3 +/- 6.2 ml/kg.min, 196 +/- 6.8 beats per min, 17 +/- 1.2 min, 56.8 +/- 6.6
      kgf, 53.1 +/- 5.9 kgf, 41.1 +/- 3.8 cm, 19.9 +/- 5.9 observed digits and 10.9 +/-
      3.1 remembered digits after drinking a placebo drink. Comparisons among the
      commercial drink, caffeine, taurine, caffeine plus taurine and placebo treatments
      did not show statistically differences in the results of the performed tests. No
      adverse effects were reported by the participants. CONCLUSION: The consumption of
      caffeine (80 mg) and taurine (1000 mg) or their combination does not increase the
      physical and cognitive ability in young adults during exercise.

PMID- 25389380
TI  - Nine-month nutritional intervention improves restoration of menses in young
      female athletes and ballet dancers.
AB  - BACKGROUND: We hypothesized that an intervention designed to increase the energy
      and nutrient intake could serve as an efficacious method to restore normal
      menstrual functions in athletes and ballet dancers. METHODS: In this study, a 9
      month nutritional intervention (NI) was conducted in 21 dancers and 31 athletes
      with menstrual disorders. Analyses of the body composition were performed, and
      the levels of LH, FSH, P, E2, TSH, T, PRL, SHBG, leptin, resting metabolic rate
      (RMR), energy and nutrient intake, total energy expenditure were estimated. The
      NI was based on an individual diet. The effects of the NI were controlled after
      3, 6 and 9 months of use. RESULTS: The NI resulted in a significant change of the
      energy and nutrient intake. After 9 months, a significant increase in the LH
      level among dancers was observed, while in female athletes this effect was seen
      after 3 months of the NI use. The 9-month NI resulted in the restoration of
      regular menses in 3 dancers and 7 athletes, respectively. Women with regular
      cycles had a higher percentage of the fat mass (FM). CONCLUSIONS: A non
      pharmacological intervention in female athletes and ballet dancers with menstrual
      disorders can restore regular menstrual cycles, although restoration of menses
      may take more than 1 year. An increase in the body fat mass may be one of the
      most important predictors of restoration of menses.

PMID- 25389381
TI  - A time-frequency analysis of the dynamics of cortical networks of sleep spindles
      from MEG-EEG recordings.
AB  - Sleep spindles are a hallmark of NREM sleep. They result from a widespread
      thalamo-cortical loop and involve synchronous cortical networks that are still
      poorly understood. We investigated whether brain activity during spindles can be
      characterized by specific patterns of functional connectivity among cortical
      generators. For that purpose, we developed a wavelet-based approach aimed at
      imaging the synchronous oscillatory cortical networks from simultaneous MEG-EEG
      recordings. First, we detected spindles on the EEG and extracted the
      corresponding frequency-locked MEG activity under the form of an analytic ridge
      signal in the time-frequency plane (Zerouali et al., 2013). Secondly, we
      performed source reconstruction of the ridge signal within the Maximum Entropy on
      the Mean framework (Amblard et al., 2004), yielding a robust estimate of the
      cortical sources producing observed oscillations. Lastly, we quantified
      functional connectivity among cortical sources using phase-locking values. The
      main innovations of this methodology are (1) to reveal the dynamic behavior of
      functional networks resolved in the time-frequency plane and (2) to characterize
      functional connectivity among MEG sources through phase interactions. We showed,
      for the first time, that the switch from fast to slow oscillatory mode during
      sleep spindles is required for the emergence of specific patterns of
      connectivity. Moreover, we show that earlier synchrony during spindles was
      associated with mainly intra-hemispheric connectivity whereas later synchrony was
      associated with global long-range connectivity. We propose that our methodology
      can be a valuable tool for studying the connectivity underlying neural processes
      involving sleep spindles, such as memory, plasticity or aging. 

PMID- 25389382
TI  - Faster and improved 3-D head digitization in MEG using Kinect.
AB  - Accuracy in localizing the brain areas that generate neuromagnetic activity in
      magnetoencephalography (MEG) is dependent on properly co-registering MEG data to
      the participant's structural magnetic resonance image (MRI). Effective MEG-MRI co
      registration is, in turn, dependent on how accurately we can digitize anatomical
      landmarks on the surface of the head. In this study, we compared the performance
      of three devices-Polhemus electromagnetic system, NextEngine laser scanner and
      Microsoft Kinect for Windows-for source localization accuracy and MEG-MRI co
      registration. A calibrated phantom was used for verifying the source localization
      accuracy. The Kinect improved source localization accuracy over the Polhemus and
      the laser scanner by 2.23 mm (137%) and 0.81 mm (50%), respectively. MEG-MRI co
      registration accuracy was verified on data from five healthy human participants,
      who received the digitization process using all three devices. The Kinect device
      captured approximately 2000 times more surface points than the Polhemus in one
      third of the time (1 min compared to 3 min) and thrice as many points as the
      NextEngine laser scanner. Following automated surface matching, the calculated
      mean MEG-MRI co-registration error for the Kinect was improved by 2.85 mm with
      respect to the Polhemus device, and equivalent to the laser scanner. Importantly,
      the Kinect device automatically aligns 20-30 images per second in real-time,
      reducing the limitations on participant head movement during digitization that
      are implicit in the NextEngine laser scan (~1 min). We conclude that the Kinect
      scanner is an effective device for head digitization in MEG, providing the
      necessary accuracy in source localization and MEG-MRI co-registration, while
      reducing digitization time. 

PMID- 25389383
TI  - Embryonic blood-cerebrospinal fluid barrier formation and function.
AB  - During embryonic development and adult life, brain cavities and ventricles are
      filled with cerebrospinal fluid (CSF). CSF has attracted interest as an active
      signaling medium that regulates brain development, homeostasis and disease. CSF
      is a complex protein-rich fluid containing growth factors and signaling molecules
      that regulate multiple cell functions in the central nervous system (CNS). The
      composition and substance concentrations of CSF are tightly controlled. In recent
      years, it has been demonstrated that embryonic CSF (eCSF) has a key function as a
      fluid pathway for delivering diffusible signals to the developing brain, thus
      contributing to the proliferation, differentiation and survival of neural
      progenitor cells, and to the expansion and patterning of the brain. From fetal
      stages through to adult life, CSF is primarily produced by the choroid plexus.
      The development and functional activities of the choroid plexus and other blood
      brain barrier (BBB) systems in adults and fetuses have been extensively analyzed.
      However, eCSF production and control of its homeostasis in embryos, from the
      closure of the anterior neuropore when the brain cavities become physiologically
      sealed, to the formation of the functional fetal choroid plexus, has not been
      studied in as much depth and remains open to debate. This review brings together
      the existing literature, some of which is based on experiments conducted by our
      research group, concerning the formation and function of a temporary embryonic
      blood-CSF barrier in the context of the crucial roles played by the molecules in
      eCSF. 

PMID- 25389384
TI  - Epigenetic changes in the estrogen receptor alpha gene promoter: implications in
      sociosexual behaviors.
AB  - Estrogen action through estrogen receptor alpha (ERalpha) is involved in the
      control of sexual and social behaviors in adult mammals. Alteration of ERalpha
      gene activity mediated by epigenetic mechanisms, such as histone modifications
      and DNA methylation, in particular brain areas appears to be crucial for
      determining the extents of these behaviors between the sexes and among
      individuals within the same sex. This review provides a summary of the epigenetic
      changes in the ERalpha gene promoter that correlate with sociosexual behaviors. 

PMID- 25389385
TI  - The myriad roles of Miro in the nervous system: axonal transport of mitochondria
      and beyond.
AB  - Mitochondrial rho GTPase (Miro) is a mitochondrial outer membrane protein
      containing two GTPase domains and two helix-loop-helix Ca(2+)-binding domains
      called EF hands. Pioneering genetic studies in Drosophila first revealed a key
      function of Miro in regulating the axonal transport of mitochondria, during which
      Miro forms a multi-protein transport complex with Milton and Kinesin heavy chain
      (KHC) to link trafficking mitochondria with the microtubule (MT) cytoskeleton.
      Recent studies showed that through binding to the EF hands of Miro and causing
      conformational changes of Miro and alteration of protein-protein interactions
      within the transport complex, Ca(2+) can alter the engagement of mitochondria
      with the MT/kinesin network, offering one mechanism to match mitochondrial
      distribution with neuronal activity. Despite the importance of the
      Miro/Milton/Kinesin complex in regulating mitochondrial transport in metazoans,
      not all components of the transport complex are conserved in lower organisms, and
      transport-independent functions of Miro are emerging. Here we review the diverse
      functions of the evolutionarily conserved Miro proteins that are relevant to the
      development, maintenance, and functioning of the nervous system and discuss the
      potential contribution of Miro dysfunction to the pathogenesis of diseases of the
      nervous system. 

PMID- 25389386
TI  - Nitric oxide from inflammatory origin impairs neural stem cell proliferation by
      inhibiting epidermal growth factor receptor signaling.
AB  - Neuroinflammation is characterized by activation of microglial cells, followed by
      production of nitric oxide (NO), which may have different outcomes on
      neurogenesis, favoring or inhibiting this process. In the present study, we
      investigated how the inflammatory mediator NO can affect proliferation of neural
      stem cells (NSCs), and explored possible mechanisms underlying this effect. We
      investigated which mechanisms are involved in the regulation of NSC proliferation
      following treatment with an inflammatory stimulus (lipopolysaccharide plus IFN
      gamma), using a culture system of subventricular zone (SVZ)-derived NSCs mixed
      with microglia cells obtained from wild-type mice (iNOS(+/+)) or from iNOS
      knockout mice (iNOS(-/-)). We found an impairment of NSC cell proliferation in
      iNOS(+/+) mixed cultures, which was not observed in iNOS(-/-) mixed cultures.
      Furthermore, the increased release of NO by activated iNOS(+/+) microglial cells
      decreased the activation of the ERK/MAPK signaling pathway, which was concomitant
      with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive
      species formation with MnTBAP, a scavenger of peroxynitrite (ONOO(-)), or using
      the ONOO(-) degradation catalyst FeTMPyP, cell proliferation and ERK signaling
      were restored to basal levels in iNOS(+/+) mixed cultures. Moreover, exposure to
      the NO donor NOC-18 (100 MUM), for 48 h, inhibited SVZ-derived NSC proliferation.
      Regarding the antiproliferative effect of NO, we found that NOC-18 caused the
      impairment of signaling through the ERK/MAPK pathway, which may be related to
      increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was
      prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO
      from inflammatory origin leads to a decreased function of the EGF receptor, which
      compromised proliferation of NSC. We also demonstrated that NO-mediated nitration
      of the EGF receptor caused a decrease in its phosphorylation, thus preventing
      regular proliferation signaling through the ERK/MAPK pathway. 

PMID- 25389388
TI  - cAMP signaling microdomains and their observation by optical methods.
AB  - The second messenger cyclic AMP (cAMP) is a major intracellular mediator of many
      hormones and neurotransmitters and regulates a myriad of cell functions,
      including synaptic plasticity in neurons. Whereas cAMP can freely diffuse in the
      cytosol, a growing body of evidence suggests the formation of cAMP gradients and
      microdomains near the sites of cAMP production, where cAMP signals remain
      apparently confined. The mechanisms responsible for the formation of such
      microdomains are subject of intensive investigation. The development of optical
      methods based on fluorescence resonance energy transfer (FRET), which allow a
      direct observation of cAMP signaling with high temporal and spatial resolution,
      is playing a fundamental role in elucidating the nature of such microdomains.
      Here, we will review the optical methods used for monitoring cAMP and protein
      kinase A (PKA) signaling in living cells, providing some examples of their
      application in neurons, and will discuss the major hypotheses on the formation of
      cAMP/PKA microdomains. 

PMID- 25389389
TI  - Commentary on "Synaptic function is modulated by LRRK2 and glutamate release is
      increased in cortical neurons of G2019S LRRK2 knock-in mice".

PMID- 25389387
TI  - The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug
      metabolism and detoxication.
AB  - UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound
      enzymes expressed in various tissues, including brain. They catalyze the
      formation of beta-D-glucuronides from structurally unrelated substances (drugs,
      other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic
      acid from the high energy donor, UDP-alpha-D-glucuronic acid. In brain, UGTs
      actively participate to the overall protection of the tissue against the
      intrusion of potentially harmful lipophilic substances that are metabolized as
      hydrophilic glucuronides. These metabolites are generally inactive, except for
      important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are
      mainly expressed in endothelial cells and astrocytes of the blood brain barrier
      (BBB). They are also associated to brain interfaces devoid of BBB, such as
      circumventricular organ, pineal gland, pituitary gland and neuro-olfactory
      tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the
      steady-state of endogenous compounds, like steroids or dopamine (DA) that
      participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and
      3A are expressed in brain tissues to various levels and are known to present
      distinct but overlapping substrate specificity. The importance of these enzyme
      species with regard to the formation of toxic, pharmacologically or
      physiologically relevant glucuronides in the brain will be discussed. 

PMID- 25389390
TI  - The pivotal role of astrocytes in an in vitro stroke model of the blood-brain
      barrier.
AB  - Stabilization of the blood-brain barrier during and after stroke can lead to less
      adverse outcome. For elucidation of underlying mechanisms and development of
      novel therapeutic strategies validated in vitro disease models of the blood-brain
      barrier could be very helpful. To mimic in vitro stroke conditions we have
      established a blood-brain barrier in vitro model based on mouse cell line
      cerebEND and applied oxygen/glucose deprivation (OGD). The role of astrocytes in
      this disease model was investigated by using cell line C6. Transwell studies
      pointed out that addition of astrocytes during OGD increased the barrier damage
      significantly in comparison to the endothelial monoculture shown by changes of
      transendothelial electrical resistance as well as fluorescein permeability data.
      Analysis on mRNA and protein levels by qPCR, western blotting and
      immunofluorescence microscopy of tight junction molecules claudin-3,-5,-12,
      occludin and ZO-1 revealed that their regulation and localisation is associated
      with the functional barrier breakdown. Furthermore, soluble factors of
      astrocytes, OGD and their combination were able to induce changes of
      functionality and expression of ABC-transporters Abcb1a (P-gp), Abcg2 (bcrp), and
      Abcc4 (mrp4). Moreover, the expression of proteases (matrixmetalloproteinases MMP
      2, MMP-3, MMP-9, and t-PA) as well as of their endogenous inhibitors (TIMP-1,
      TIMP-3, PAI-1) was altered by astrocyte factors and OGD which resulted in
      significant changes of total MMP and t-PA activity. Morphological rearrangements
      induced by OGD and treatment with astrocyte factors were confirmed at a nanometer
      scale using atomic force microscopy. In conclusion, astrocytes play a major role
      in blood-brain barrier breakdown during OGD in vitro. 

PMID- 25389391
TI  - Neuromodulatory adaptive combination of correlation-based learning in cerebellum
      and reward-based learning in basal ganglia for goal-directed behavior control.
AB  - Goal-directed decision making in biological systems is broadly based on
      associations between conditional and unconditional stimuli. This can be further
      classified as classical conditioning (correlation-based learning) and operant
      conditioning (reward-based learning). A number of computational and experimental
      studies have well established the role of the basal ganglia in reward-based
      learning, where as the cerebellum plays an important role in developing specific
      conditioned responses. Although viewed as distinct learning systems, recent
      animal experiments point toward their complementary role in behavioral learning,
      and also show the existence of substantial two-way communication between these
      two brain structures. Based on this notion of co-operative learning, in this
      paper we hypothesize that the basal ganglia and cerebellar learning systems work
      in parallel and interact with each other. We envision that such an interaction is
      influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the
      thalamus, guiding the overall goal directed behavior. Using a recurrent neural
      network actor-critic model of the basal ganglia and a feed-forward correlation
      based learning model of the cerebellum, we demonstrate that the RMHP rule can
      effectively balance the outcomes of the two learning systems. This is tested
      using simulated environments of increasing complexity with a four-wheeled robot
      in a foraging task in both static and dynamic configurations. Although modeled
      with a simplified level of biological abstraction, we clearly demonstrate that
      such a RMHP induced combinatorial learning mechanism, leads to stabler and faster
      learning of goal-directed behaviors, in comparison to the individual systems.
      Thus, in this paper we provide a computational model for adaptive combination of
      the basal ganglia and cerebellum learning systems by way of neuromodulated
      plasticity for goal-directed decision making in biological and bio-mimetic
      organisms.

PMID- 25389392
TI  - Motion as a source of environmental information: a fresh view on biological
      motion computation by insect brains.
AB  - Despite their miniature brains insects, such as flies, bees and wasps, are able
      to navigate by highly erobatic flight maneuvers in cluttered environments. They
      rely on spatial information that is contained in the retinal motion patterns
      induced on the eyes while moving around ("optic flow") to accomplish their
      extraordinary performance. Thereby, they employ an active flight and gaze
      strategy that separates rapid saccade-like turns from translatory flight phases
      where the gaze direction is kept largely constant. This behavioral strategy
      facilitates the processing of environmental information, because information
      about the distance of the animal to objects in the environment is only contained
      in the optic flow generated by translatory motion. However, motion detectors as
      are widespread in biological systems do not represent veridically the velocity of
      the optic flow vectors, but also reflect textural information about the
      environment. This characteristic has often been regarded as a limitation of a
      biological motion detection mechanism. In contrast, we conclude from analyses
      challenging insect movement detectors with image flow as generated during
      translatory locomotion through cluttered natural environments that this mechanism
      represents the contours of nearby objects. Contrast borders are a main carrier of
      functionally relevant object information in artificial and natural sceneries. The
      motion detection system thus segregates in a computationally parsimonious way the
      environment into behaviorally relevant nearby objects and-in many behavioral
      contexts-less relevant distant structures. Hence, by making use of an active
      flight and gaze strategy, insects are capable of performing extraordinarily well
      even with a computationally simple motion detection mechanism.

PMID- 25389393
TI  - On the temporal organization of neuronal avalanches.
AB  - Spontaneous activity of cortex in vitro and in vivo has been shown to organize as
      neuronal avalanches. Avalanches are cascades of neuronal activity that exhibit a
      power law in their size and duration distribution, typical features of balanced
      systems in a critical state. Recently it has been shown that the distribution of
      quiet times between consecutive avalanches in rat cortex slice cultures displays
      a non-monotonic behavior with a power law decay at short time scales. This
      behavior has been attributed to the slow alternation between up and down-states.
      Here we further characterize the avalanche process and investigate how the
      functional behavior of the quiet time distribution depends on the fine structure
      of avalanche sequences. By systematically removing smaller avalanches from the
      experimental time series we show that size and quiet times are correlated and
      highlight that avalanche occurrence exhibits the characteristic periodicity of
      theta and beta/gamma oscillations, which jointly emerge in most of the analyzed
      samples. Furthermore, our analysis indicates that smaller avalanches tend to be
      associated with faster beta/gamma oscillations, whereas larger ones are
      associated with slower theta and 1-2 Hz oscillations. In particular, large
      avalanches corresponding to theta cycles trigger cascades of smaller ones, which
      occur at beta/gamma frequency. This temporal structure follows closely the one of
      nested theta - beta/gamma oscillations. Finally we demonstrate that, because of
      the multiple time scales characterizing avalanche dynamics, the distributions of
      quiet times between avalanches larger than a certain size do not collapse onto a
      unique function when rescaled by the average occurrence rate. However, when
      considered separately in the up-state and in the down-state, these distributions
      are solely controlled by the respective average rate and two different unique
      function can be identified. 

PMID- 25389394
TI  - Enhancement of sleep slow waves: underlying mechanisms and practical
      consequences.
AB  - Even modest sleep restriction, especially the loss of sleep slow wave activity
      (SWA), is invariably associated with slower electroencephalogram (EEG) activity
      during wake, the occurrence of local sleep in an otherwise awake brain, and
      impaired performance due to cognitive and memory deficits. Recent studies not
      only confirm the beneficial role of sleep in memory consolidation, but also point
      to a specific role for sleep slow waves. Thus, the implementation of methods to
      enhance sleep slow waves without unwanted arousals or lightening of sleep could
      have significant practical implications. Here we first review the evidence that
      it is possible to enhance sleep slow waves in humans using transcranial direct
      current stimulation (tDCS) and transcranial magnetic stimulation. Since these
      methods are currently impractical and their safety is questionable, especially
      for chronic long-term exposure, we then discuss novel data suggesting that it is
      possible to enhance slow waves using sensory stimuli. We consider the physiology
      of the K-complex (KC), a peripheral evoked slow wave, and show that, among
      different sensory modalities, acoustic stimulation is the most effective in
      increasing the magnitude of slow waves, likely through the activation of non
      lemniscal ascending pathways to the thalamo-cortical system. In addition, we
      discuss how intensity and frequency of the acoustic stimuli, as well as exact
      timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss
      automated algorithms that read the EEG and, in real-time, adjust the stimulation
      parameters in a closed-loop manner to obtain an increase in sleep slow waves and
      avoid undesirable arousals. In conclusion, while discussing the mechanisms that
      underlie the generation of sleep slow waves, we review the converging evidence
      showing that acoustic stimulation is safe and represents an ideal tool for slow
      wave sleep (SWS) enhancement. 

PMID- 25389395
TI  - Role of dopamine D2 receptors in optimizing choice strategy in a dynamic and
      uncertain environment.
AB  - In order to investigate roles of dopamine receptor subtypes in reward-based
      learning, we examined choice behavior of dopamine D1 and D2 receptor-knockout
      (D1R-KO and D2R-KO, respectively) mice in an instrumental learning task with
      progressively increasing reversal frequency and a dynamic two-armed bandit task.
      Performance of D2R-KO mice was progressively impaired in the former as the
      frequency of reversal increased and profoundly impaired in the latter even with
      prolonged training, whereas D1R-KO mice showed relatively minor performance
      deficits. Choice behavior in the dynamic two-armed bandit task was well explained
      by a hybrid model including win-stay-lose-switch and reinforcement learning
      terms. A model-based analysis revealed increased win-stay, but impaired value
      updating and decreased value-dependent action selection in D2R-KO mice, which
      were detrimental to maximizing rewards in the dynamic two-armed bandit task.
      These results suggest an important role of dopamine D2 receptors in learning from
      past choice outcomes for rapid adjustment of choice behavior in a dynamic and
      uncertain environment. 

PMID- 25389396
TI  - Brain activation associated with active and passive lower limb stepping.
AB  - Reports about standardized and repeatable experimental procedures investigating
      supraspinal activation in patients with gait disorders are scarce in current
      neuro-imaging literature. Well-designed and executed tasks are important to gain
      insight into the effects of gait-rehabilitation on sensorimotor centers of the
      brain. The present study aims to demonstrate the feasibility of a novel imaging
      paradigm, combining the magnetic resonance (MR)-compatible stepping robot
      (MARCOS) with sparse sampling functional magnetic resonance imaging (fMRI) to
      measure task-related BOLD signal changes and to delineate the supraspinal
      contribution specific to active and passive stepping. Twenty-four healthy
      participants underwent fMRI during active and passive, periodic, bilateral, multi
      joint, lower limb flexion and extension akin to human gait. Active and passive
      stepping engaged several cortical and subcortical areas of the sensorimotor
      network, with higher relative activation of those areas during active movement.
      Our results indicate that the combination of MARCOS and sparse sampling fMRI is
      feasible for the detection of lower limb motor related supraspinal activation.
      Activation of the anterior cingulate and medial frontal areas suggests motor
      response inhibition during passive movement in healthy participants. Our results
      are of relevance for understanding the neural mechanisms underlying gait in the
      healthy. 

PMID- 25389397
TI  - Amygdala and Dorsal Anterior Cingulate Connectivity during an Emotional Working
      Memory Task in Borderline Personality Disorder Patients with Interpersonal Trauma
      History.
AB  - Working memory is critically involved in ignoring emotional distraction while
      maintaining goal-directed behavior. Antagonistic interactions between brain
      regions implicated in emotion processing, e.g., amygdala, and brain regions
      involved in cognitive control, e.g., dorsolateral and dorsomedial prefrontal
      cortex (dlPFC, dmPFC), may play an important role in coping with emotional
      distraction. We previously reported prolonged reaction times associated with
      amygdala hyperreactivity during emotional distraction in interpersonally
      traumatized borderline personality disorder (BPD) patients compared to healthy
      controls (HC): Participants performed a working memory task, while neutral versus
      negative distractors (interpersonal scenes from the International Affective
      Picture System) were presented. Here, we re-analyzed data from this study using
      psychophysiological interaction analysis. The bilateral amygdala and bilateral
      dorsal anterior cingulate cortex (dACC) were defined as seed regions of interest.
      Whole-brain regression analyses with reaction times and self-reported increase of
      dissociation were performed. During emotional distraction, reduced amygdala
      connectivity with clusters in the left dorsolateral and ventrolateral PFC was
      observed in the whole group. Compared to HC, BPD patients showed a stronger
      coupling of both seeds with a cluster in the right dmPFC and stronger positive
      amygdala connectivity with bilateral (para)hippocampus. Patients further
      demonstrated stronger positive dACC connectivity with left posterior cingulate,
      insula, and frontoparietal regions during emotional distraction. Reaction times
      positively predicted amygdala connectivity with right dmPFC and
      (para)hippocampus, while dissociation positively predicted amygdala connectivity
      with right ACC during emotional distraction in patients. Our findings suggest
      increased attention to task-irrelevant (emotional) social information during a
      working memory task in interpersonally traumatized patients with BPD. 

PMID- 25389398
TI  - Causal reasoning with mental models.
AB  - This paper outlines the model-based theory of causal reasoning. It postulates
      that the core meanings of causal assertions are deterministic and refer to
      temporally-ordered sets of possibilities: A causes B to occur means that given A,
      B occurs, whereas A enables B to occur means that given A, it is possible for B
      to occur. The paper shows how mental models represent such assertions, and how
      these models underlie deductive, inductive, and abductive reasoning yielding
      explanations. It reviews evidence both to corroborate the theory and to account
      for phenomena sometimes taken to be incompatible with it. Finally, it reviews
      neuroscience evidence indicating that mental models for causal inference are
      implemented within lateral prefrontal cortex. 

PMID- 25389399
TI  - How visual illusions illuminate complementary brain processes: illusory depth
      from brightness and apparent motion of illusory contours.
AB  - Neural models of perception clarify how visual illusions arise from adaptive
      neural processes. Illusions also provide important insights into how adaptive
      neural processes work. This article focuses on two illusions that illustrate a
      fundamental property of global brain organization; namely, that advanced brains
      are organized into parallel cortical processing streams with computationally
      complementary properties. That is, in order to process certain combinations of
      properties, each cortical stream cannot process complementary properties.
      Interactions between these streams, across multiple processing stages, overcome
      their complementary deficiencies to compute effective representations of the
      world, and to thereby achieve the property of complementary consistency. The two
      illusions concern how illusory depth can vary with brightness, and how apparent
      motion of illusory contours can occur. Illusory depth from brightness arises from
      the complementary properties of boundary and surface processes, notably boundary
      completion and surface-filling in, within the parvocellular form processing
      cortical stream. This illusion depends upon how surface contour signals from the
      V2 thin stripes to the V2 interstripes ensure complementary consistency of a
      unified boundary/surface percept. Apparent motion of illusory contours arises
      from the complementary properties of form and motion processes across the
      parvocellular and magnocellular cortical processing streams. This illusion
      depends upon how illusory contours help to complete boundary representations for
      object recognition, how apparent motion signals can help to form continuous
      trajectories for target tracking and prediction, and how formotion interactions
      from V2-to-MT enable completed object representations to be continuously tracked
      even when they move behind intermittently occluding objects through time. 

PMID- 25389400
TI  - Geometrical illusions are not always where you think they are: a review of some
      classical and less classical illusions, and ways to describe them.
AB  - Geometrical illusions are known through a small core of classical illusions that
      were discovered in the second half of the nineteenth century. Most experimental
      studies and most theoretical discussions revolve around this core of illusions,
      as though all other illusions were obvious variants of these. Yet, many
      illusions, mostly described by German authors at the same time or at the
      beginning of the twentieth century have been forgotten and are awaiting their
      rehabilitation. Recently, several new illusions were discovered, mainly by
      Italian authors, and they do not seem to take place into any current
      classification. Among the principles that are invoked to explain the illusions,
      there are principles relating to the metric aspects (contrast, assimilation,
      shrinkage, expansion, attraction of parallels) principles relating to
      orientations (regression to right angles, orthogonal expansion) or, more
      recently, to gestalt effects. Here, metric effects are discussed within a
      measurement framework, in which the geometric illusions are the outcome of a
      measurement process. There would be a main "convexity" bias in the measures: the
      measured value m(x) of an extant x would grow more than proportionally with x.
      This convexity principle, completed by a principle of compromise for conflicting
      measures can replace, for a large number of patterns, both the assimilation and
      the contrast effects. We know from evolutionary theory that the most pertinent
      classification criteria may not be the most salient ones (e.g., a dolphin is not
      a fish). In order to obtain an objective classification of illusions, I initiated
      with Kevin O'Regan systematic work on "orientation profiles" (describing how the
      strength of an illusion varies with its orientation in the plane). We showed
      first that the Zollner illusion already exists at the level of single stacks, and
      that it does not amount to a rotation of the stacks. Later work suggested that it
      is best described by an "orthogonal expansion"-an expansion of the stacks applied
      orthogonally to the oblique segments of the stacks, generating an apparent
      rotation effect. We showed that the Poggendorff illusion was mainly a
      misangulation effect. We explained the hierarchy of the illusion magnitudes found
      among variants of the Poggendorff illusion by the existence of control devices
      that counteract the loss of parallelism or the loss of collinearity produced by
      the biased measurements. I then studied the trapezium illusion. The oblique
      sides, but not the bases, were essential to the trapezium illusion, suggesting
      the existence of a common component between the trapezium and the Zollner
      illusion. Unexpectedly, the trapeziums sometimes appeared as twisted surfaces in
      3d. It also appeared impossible, using a nulling procedure, to make all
      corresponding sides of two trapeziums simultaneously equal. The square-diamond
      illusion is usually presented with one apex of the diamond pointing toward the
      square. I found that when the figures were displayed more symmetrically, the
      illusion was significantly reduced. Furthermore, it is surpassed, for all
      subjects, by an illusion that goes in the opposite direction, in which the
      diagonal of a small diamond is underestimated with respect to the side of a
      larger square. In general, the experimental work generated many unexpected
      results. Each illusory stimulus was compared to a number of control variants, and
      often, I measured larger distortions in a variant than in the standard stimulus.
      In the Discussion, I will stress what I think are the main ordering principle in
      the metric and the orientation domains for illusory patterns. The convexity bias
      principle and the orthogonal expansion principles help to establish unsuspected
      links between apparently unrelated stimuli, and reduce their apparently extreme
      heterogeneity. However, a number of illusions (e.g., those of the twisted cord
      family, or the Poggendorff illusions) remain unpredicted by the above principles.
      Finally, I will develop the idea that the brain is constructing several
      representations, and the one that is commonly used for the purpose of shape
      perception generates distortions inasmuch as it must satisfy a number of
      conflicting constraints, such as the constraint of producing a stable shape
      despite the changing perspectives produced by eye movements. 

PMID- 25389401
TI  - Directional interactions between current and prior saccades.
AB  - One way to explore how prior sensory and motor events impact eye movements is to
      ask someone to look to targets located about a central point, returning gaze to
      the central point after each eye movement. Concerned about the contribution of
      this return to center movement, Anderson et al. (2008) used a sequential saccade
      paradigm in which participants made a continuous series of saccades to peripheral
      targets that appeared to the left or right of the currently fixated location in a
      random sequence (the next eye movement began from the last target location).
      Examining the effects of previous saccades (n-x) on current saccade latency (n),
      they found that saccadic reaction times (RT) were reduced when the direction of
      the current saccade matched that of a preceding saccade (e.g., two left
      saccades), even when the two saccades in question were separated by multiple
      saccades in any direction. We examined if this pattern extends to conditions in
      which targets appear inside continuously marked locations that provide stable
      visual features (i.e., target "placeholders") and when saccades are prompted by
      central arrows. Participants completed 3 conditions: peripheral targets (PT;
      continuous, sequential saccades to peripherally presented targets) without
      placeholders; PT with placeholders; and centrally presented arrows (CA; left or
      right pointing arrows at the currently fixated location instructing participants
      to saccade to the left or right). We found reduced saccadic RT when the
      immediately preceding saccade (n-1) was in the same (vs. opposite) direction in
      the PT without placeholders and CA conditions. This effect varied when
      considering the effect of the previous 2-5 (n-x) saccades on current saccade
      latency (n). The effects of previous eye movements on current saccade latency may
      be determined by multiple, time-varying mechanisms related to sensory (i.e.,
      retinotopic location), motor (i.e., saccade direction), and environmental (i.e.,
      persistent visual objects) factors. 

PMID- 25389402
TI  - An emotion regulation role of ventromedial prefrontal cortex in moral judgment.

PMID- 25389403
TI  - The benefits of endurance exercise and Tai Chi Chuan for the task-switching
      aspect of executive function in older adults: an ERP study.
AB  - This study was designed to determine the relationship between physical activity
      and the task-switching aspect of executive function by investigating the
      modulating roles of age, modality of physical activity, and type of cognitive
      function using behavioral and event-related potential (ERP) assessments. Sixty
      four participants were assigned to one of four groups based on age and history of
      physical activity: older adults performing endurance exercise (OEE), older adults
      practicing Tai Chi Chuan (OTC), older adults with a sedentary lifestyle (OSL),
      and young adults (YA). Study participants completed a task-switching task under
      homogeneous and heterogeneous conditions while ERPs were recorded. The results
      revealed that YA had shortest reaction times compared with the three older adults
      groups, with OSL exhibiting the longest reaction time. YA also exhibited shorter
      P3 latency than OSL. No differences were observed in P3 amplitude between YA,
      OEE, and OTC; however, all three groups had significantly larger P3 amplitude
      compared with OSL in both task conditions. In conclusion, age and participation
      in physical activity influence the relationship between physical activity and
      task-switching, and a positive relationship was observed regardless of the
      modality of physical activity and type of cognitive function. Our ERP findings
      support the model of the scaffolding theory of aging and cognition (STAC) and
      suggest that regular participation in endurance exercise and Tai Chi Chuan may
      have equivalent beneficial effects on cognition at the behavioral and
      neuroelectric levels. 

PMID- 25389404
TI  - Preclinical and clinical issues in Alzheimer's disease drug research and
      development.

PMID- 25389405
TI  - The inducible caspase-9 suicide gene system as a "safety switch" to limit on
      target, off-tumor toxicities of chimeric antigen receptor T cells.
AB  - Immune modulation has become a central element in many cancer treatments, and T
      cells genetically engineered to express chimeric antigen receptors (CAR) may
      provide a new approach to cancer immunotherapy. Autologous CAR T cells that have
      been re-directed toward tumor-associated antigens (TAA) have shown promising
      results in phase 1 clinical trials, with some patients undergoing complete tumor
      regression. However, this T-cell therapy must carefully balance effective T-cell
      activation, to ensure antitumor activity, with the potential for uncontrolled
      activation that may produce immunopathology. An inducible Caspase 9 (iCasp9)
      "safety switch" offers a solution that allows for the removal of inappropriately
      activated CAR T cells. The induction of iCasp9 depends on the administration of
      the small molecule dimerizer drug AP1903 and dimerization results in rapid
      induction of apoptosis in transduced cells, preferentially killing activated
      cells expressing high levels of transgene. The iCasp9 gene has been incorporated
      into vectors for use in preclinical studies and demonstrates effective and
      reliable suicide gene activity in phase 1 clinical trials. A third-generation CAR
      incorporating iCasp9 re-directs T cells toward the GD2 TAA. GD2 is over-expressed
      in melanoma and other malignancies of neural crest origin and the safety and
      activity of these GD2-iCAR T cells will be investigated in CARPETS and other
      actively recruiting phase 1 trials. 

PMID- 25389407
TI  - Task-dependent inhibition of slow-twitch soleus and excitation of fast-twitch
      gastrocnemius do not require high movement speed and velocity-dependent sensory
      feedback.
AB  - Although individual heads of triceps surae, soleus (SO) and medial gastrocnemius
      (MG) muscles, are often considered close functional synergists, previous studies
      have shown distinct activity patterns between them in some motor behaviors. The
      goal of this study was to test two hypotheses explaining inhibition of slow SO
      with respect to fast MG: (1) inhibition occurs at high movement velocities and
      mediated by velocity-dependent sensory feedback and (2) inhibition depends on the
      ankle-knee joint moment combination and does not require high movement
      velocities. The hypotheses were tested by comparing the SO EMG/MG EMG ratio
      during fast and slow motor behaviors (cat paw shake responses vs. back, straight
      leg load lifting in humans), which had the same ankle extension-knee flexion
      moment combination; and during fast and slow behaviors with the ankle extension
      knee extension moment combination (human vertical jumping and stance phase of
      walking in cats and leg load lifting in humans). In addition, SO EMG/MG EMG ratio
      was determined during cat paw shake responses and walking before and after
      removal of stretch velocity-dependent sensory feedback by self-reinnervating SO
      and/or gastrocnemius. We found the ratio SO EMG/MG EMG below 1 (p < 0.05) during
      fast paw shake responses and slow back load lifting, requiring the ankle
      extension-knee flexion moment combination; whereas the ratio SO EMG/MG EMG was
      above 1 (p < 0.05) during fast vertical jumping and slow tasks of walking and leg
      load lifting, requiring ankle extension-knee extension moments. Removal of
      velocity-dependent sensory feedback did not affect the SO EMG/MG EMG ratio in
      cats. We concluded that the relative inhibition of SO does not require high
      muscle velocities, depends on ankle-knee moment combinations, and is mechanically
      advantageous for allowing a greater MG contribution to ankle extension and knee
      flexion moments. 

PMID- 25389406
TI  - Revisiting cAMP signaling in the carotid body.
AB  - Chronic carotid body (CB) activation is now recognized as being essential in the
      development of hypertension and promoting insulin resistance; thus, it is
      imperative to characterize the chemotransduction mechanisms of this organ in
      order to modulate its activity and improve patient outcomes. For several years,
      and although controversial, cyclic adenosine monophosphate (cAMP) was considered
      an important player in initiating the activation of the CB. However, its
      relevance was partially displaced in the 90s by the emerging role of the
      mitochondria and molecules such as AMP-activated protein kinase and O2-sensitive
      K(+) channels. Neurotransmitters/neuromodulators binding to metabotropic
      receptors are essential to chemotransmission in the CB, and cAMP is central to
      this process. cAMP also contributes to raise intracellular Ca(2+) levels, and is
      intimately related to the cellular energetic status (AMP/ATP ratio). Furthermore,
      cAMP signaling is a target of multiple current pharmacological agents used in
      clinical practice. This review (1) provides an outline on the classical view of
      the cAMP-signaling pathway in the CB that originally supported its role in the
      O2/CO2 sensing mechanism, (2) presents recent evidence on CB cAMP neuromodulation
      and (3) discusses how CB activity is affected by current clinical therapies that
      modify cAMP-signaling, namely dopaminergic drugs, caffeine (modulation of A2A/A2B
      receptors) and roflumilast (PDE4 inhibitors). cAMP is key to any process that
      involves metabotropic receptors and the intracellular pathways involved in CB
      disease states are likely to involve this classical second messenger. Research
      examining the potential modification of cAMP levels and/or interactions with
      molecules associated with CB hyperactivity is currently in its beginning and this
      review will open doors for future explorations. 

PMID- 25389408
TI  - Oscillatory behavior of ventricular action potential duration in heart failure
      patients at respiratory rate and low frequency.
AB  - Oscillations of arterial pressure occur spontaneously at a frequency of
      approximately 0.1 Hz coupled with synchronous oscillations of sympathetic nerve
      activity ("Mayer waves"). This study investigated the extent to which
      corresponding oscillations may occur in ventricular action potential duration
      (APD). Fourteen ambulatory (outpatient) heart failure patients with biventricular
      pacing devices were studied while seated upright watching movie clips to maintain
      arousal. Activation recovery intervals (ARI) as a measure of ventricular APD were
      obtained from unipolar electrograms recorded from the LV epicardial pacing lead
      during steady state RV pacing from the device. Arterial blood pressure was
      measured non-invasively (Finapress) and respiration monitored. Oscillations were
      quantified using time frequency and coherence analysis. Oscillatory behavior of
      ARI at the respiratory frequency was observed in all subjects. The magnitude of
      the ARI variation ranged from 2.2 to 6.9 ms (mean 5.0 ms). Coherence analysis
      showed a correlation with respiratory oscillation for an average of 43% of the
      recording time at a significance level of p < 0.05. Oscillations in systolic
      blood pressure in the Mayer wave frequency range were observed in all subjects
      for whom blood pressure was recorded (n = 13). ARI oscillation in the Mayer wave
      frequency range was observed in 6/13 subjects (46%) over a range of 2.9 to 9.2
      ms. Coherence with Mayer waves at the p < 0.05 significance level was present for
      an average of 29% of the recording time. In ambulatory patients with heart
      failure during enhanced mental arousal, left ventricular epicardial APD (ARI)
      oscillated at the respiratory frequency (approximately 0.25 Hz). In 6 patients
      (46%) APD oscillated at the slower Mayer wave frequency (approximately 0.1 Hz).
      These findings may be important in understanding sympathetic activity-related
      arrhythmogenesis. 

PMID- 25389410
TI  - Perception of visual advertising in different media: from attention to
      distraction, persuasion, preference and memory.

PMID- 25389409
TI  - Haptoglobin, hemopexin, and related defense pathways-basic science, clinical
      perspectives, and drug development.
AB  - Hemolysis, which occurs in many disease states, can trigger a diverse
      pathophysiologic cascade that is related to the specific biochemical activities
      of free Hb and its porphyrin component heme. Normal erythropoiesis and
      concomitant removal of senescent red blood cells (RBC) from the circulation
      occurs at rates of approximately 2 * 10(6) RBCs/second. Within this physiologic
      range of RBC turnover, a small fraction of hemoglobin (Hb) is released into
      plasma as free extracellular Hb. In humans, there is an efficient multicomponent
      system of Hb sequestration, oxidative neutralization and clearance. Haptoglobin
      (Hp) is the primary Hb-binding protein in human plasma, which attenuates the
      adverse biochemical and physiologic effects of extracellular Hb. The cellular
      receptor target of Hp is the monocyte/macrophage scavenger receptor, CD163.
      Following Hb-Hp binding to CD163, cellular internalization of the complex leads
      to globin and heme metabolism, which is followed by adaptive changes in
      antioxidant and iron metabolism pathways and macrophage phenotype polarization.
      When Hb is released from RBCs within the physiologic range of Hp, the potential
      deleterious effects of Hb are prevented. However, during hyper-hemolytic
      conditions or with chronic hemolysis, Hp is depleted and Hb readily distributes
      to tissues where it might be exposed to oxidative conditions. In such conditions,
      heme can be released from ferric Hb. The free heme can then accelerate tissue
      damage by promoting peroxidative reactions and activation of inflammatory
      cascades. Hemopexin (Hx) is another plasma glycoprotein able to bind heme with
      high affinity. Hx sequesters heme in an inert, non-toxic form and transports it
      to the liver for catabolism and excretion. In the present review we discuss the
      components of physiologic Hb/heme detoxification and their potential therapeutic
      application in a wide range of hemolytic conditions. 

PMID- 25389411
TI  - Chill-inducing music enhances altruism in humans.
AB  - Music is a universal feature of human cultures, and it has both fascinated and
      troubled many researchers. In this paper we show through the dictator game (DG)
      that an individual's listening to preferred "chill-inducing" music may promote
      altruistic behavior that extends beyond the bounds of kin selection or reciprocal
      altruism. Participants were 22 undergraduate and postgraduate students who were
      divided into two groups, the in-group and the out-group, and they acted as
      dictators. The dictators listened to their own preferred "chill-inducing" music,
      to music they disliked, or to silence, and then played the DG. In this
      hypothetical experiment, the dictators were given real money (which they did not
      keep) and were asked to distribute it to the recipients, who were presented as
      stylized images of men and women displayed on a computer screen. The dictators
      played the DG both before and after listening to the music. Both male and female
      dictators gave more money after listening to their preferred music and less after
      listening to the music they disliked, whereas silence had no effect on the
      allocated amounts. The group to which the recipient belonged did not influence
      these trends. The results suggest that listening to preferred "chill-inducing"
      music promotes altruistic behavior. 

PMID- 25389412
TI  - Anorexia and attachment: dysregulated defense and pathological mourning.
AB  - The role of defensive exclusion (Deactivation and Segregated Systems) in the
      development of early relationships and related to subsequent manifestations of
      symptoms of eating disorders was assessed using the Adult Attachment Projective
      Picture System (AAP). Fifty-one DSM-IV diagnosed women with anorexia participated
      in the study. Anorexic patients were primarily classified as dismissing or
      unresolved. Quantitative and qualitative analyses of defensive exclusion were
      carried out. Results showed potential benefits of using the AAP defense exclusion
      coding system, in addition to the main attachment classifications, in order to
      better understand the developmental issues involved in anorexia. Discussion
      concerned the processes, such as pathological mourning, that may underlie the
      associations between dismissing and unresolved attachment and anorexia.
      Implications for developmental research and clinical nosology are discussed. 

PMID- 25389413
TI  - Common microRNAs Target Established ASD Genes.

PMID- 25389414
TI  - Beyond crossing fibers: bootstrap probabilistic tractography using complex
      subvoxel fiber geometries.
AB  - Diffusion magnetic resonance imaging fiber tractography is a powerful tool for
      investigating human white matter connectivity in vivo. However, it is prone to
      false positive and false negative results, making interpretation of the
      tractography result difficult. Optimal tractography must begin with an accurate
      description of the subvoxel white matter fiber structure, includes quantification
      of the uncertainty in the fiber directions obtained, and quantifies the
      confidence in each reconstructed fiber tract. This paper presents a novel and
      comprehensive pipeline for fiber tractography that meets the above requirements.
      The subvoxel fiber geometry is described in detail using a technique that allows
      not only for straight crossing fibers but for fibers that curve and splay. This
      technique is repeatedly performed within a residual bootstrap statistical process
      in order to efficiently quantify the uncertainty in the subvoxel geometries
      obtained. A robust connectivity index is defined to quantify the confidence in
      the reconstructed connections. The tractography pipeline is demonstrated in the
      human brain. 

PMID- 25389415
TI  - Identification of pre-spike network in patients with mesial temporal lobe
      epilepsy.
AB  - BACKGROUND: Seizures and interictal spikes in mesial temporal lobe epilepsy
      (MTLE) affect a network of brain regions rather than a single epileptic focus.
      Simultaneous electroencephalography and functional magnetic resonance imaging
      (EEG-fMRI) studies have demonstrated a functional network in which hemodynamic
      changes are time-locked to spikes. However, whether this reflects the propagation
      of neuronal activity from a focus, or conversely the activation of a network
      linked to spike generation remains unknown. The functional connectivity (FC)
      changes prior to spikes may provide information about the connectivity changes
      that lead to the generation of spikes. We used EEG-fMRI to investigate FC changes
      immediately prior to the appearance of interictal spikes on EEG in patients with
      MTLE. METHODS/PRINCIPAL FINDINGS: Fifteen patients with MTLE underwent continuous
      EEG-fMRI during rest. Spikes were identified on EEG and three 10 s epochs were
      defined relative to spike onset: spike (0-10 s), pre-spike (-10 to 0 s), and rest
      (-20 to -10 s, with no previous spikes in the preceding 45s). Significant spike
      related activation in the hippocampus ipsilateral to the seizure focus was found
      compared to the pre-spike and rest epochs. The peak voxel within the hippocampus
      ipsilateral to the seizure focus was used as a seed region for FC analysis in the
      three conditions. A significant change in FC patterns was observed before the
      appearance of electrographic spikes. Specifically, there was significant loss of
      coherence between both hippocampi during the pre-spike period compared to spike
      and rest states. CONCLUSION/SIGNIFICANCE: In keeping with previous findings of
      abnormal inter-hemispheric hippocampal connectivity in MTLE, our findings
      specifically link reduced connectivity to the period immediately before spikes.
      This brief decoupling is consistent with a deficit in mutual (inter-hemispheric)
      hippocampal inhibition that may predispose to spike generation.

PMID- 25389416
TI  - Multiplexed Detection of O-GlcNAcome, Phosphoproteome, and Whole Proteome within
      the Same Gel.
AB  - The cellular diversity of proteins results in part from their post-translational
      modifications. Among all of them, the O-GlcNAcylation is an atypical
      glycosylation, more similar to phosphorylation than classical glycosylations.
      Highly dynamic, reversible, and exclusively localized on cytosolic, nuclear, and
      mitochondrial proteins, O-GlcNAcylation is known to regulate almost all if not
      all cellular processes. Fundamental for the cell life, O-GlcNAcylation
      abnormalities are involved in the etiology of several inherited diseases.
      Assessing to O-GlcNAcylation pattern will permit to get relevant data about the
      role of O-GlcNAcylation in cell physiology. To get understanding about the role
      of O-GlcNAcylation, as also considering its interplay with phosphorylation, the O
      GlcNAc profiling remains a real challenge for the community of
      proteomists/glycoproteomists. The development of multiplexed proteomics based on
      fluorescent detection of proteins permits to go further in the understanding of
      the proteome complexity. We propose herein a multiplexed proteomic strategy to
      detect O-GlcNAcylated proteins, phosphoproteins, and the whole proteome within
      the same bidimensional gel. In particular, we investigated the phosphoproteome
      through the ProQ Diamond staining, while the whole proteome was visualized
      through Sypro Ruby staining, or after the labeling of proteins with a T-Dye
      fluorophore. The O-GlcNAcome was revealed by the way of the Click chemistry and
      the azide-alkyne cycloaddition of a fluorophore on GlcNAc moieties. This method
      permits, after sequential image acquisition, the direct in-gel detection of O
      GlcNAcome, phosphoproteome, and whole proteome. 

PMID- 25389417
TI  - Microbial eukaryote diversity in the marine oxygen minimum zone off northern
      Chile.
AB  - Molecular surveys are revealing diverse eukaryotic assemblages in oxygen-limited
      ocean waters. These communities may play pivotal ecological roles through
      autotrophy, feeding, and a wide range of symbiotic associations with prokaryotes.
      We used 18S rRNA gene sequencing to provide the first snapshot of pelagic
      microeukaryotic community structure in two cellular size fractions (0.2-1.6 MUm,
      >1.6 MUm) from seven depths through the anoxic oxygen minimum zone (OMZ) off
      northern Chile. Sequencing of >154,000 amplicons revealed contrasting patterns of
      phylogenetic diversity across size fractions and depths. Protist and total
      eukaryote diversity in the >1.6 MUm fraction peaked at the chlorophyll maximum in
      the upper photic zone before declining by ~50% in the OMZ. In contrast, diversity
      in the 0.2-1.6 MUm fraction, though also elevated in the upper photic zone,
      increased four-fold from the lower oxycline to a maximum at the anoxic OMZ core.
      Dinoflagellates of the Dinophyceae and endosymbiotic Syndiniales clades dominated
      the protist assemblage at all depths (~40-70% of sequences). Other protist groups
      varied with depth, with the anoxic zone community of the larger size fraction
      enriched in euglenozoan flagellates and acantharean radiolarians (up to 18 and
      40% of all sequences, respectively). The OMZ 0.2-1.6 MUm fraction was dominated
      (11-99%) by Syndiniales, which exhibited depth-specific variation in composition
      and total richness despite uniform oxygen conditions. Metazoan sequences, though
      confined primarily to the 1.6 MUm fraction above the OMZ, were also detected
      within the anoxic zone where groups such as copepods increased in abundance
      relative to the oxycline and upper OMZ. These data, compared to those from other
      low-oxygen sites, reveal variation in OMZ microeukaryote composition, helping to
      identify clades with potential adaptations to oxygen-depletion. 

PMID- 25389419
TI  - Characterization and comparative analysis of antibiotic resistance plasmids
      isolated from a wastewater treatment plant.
AB  - A wastewater treatment plant (WWTP) is an environment high in nutrient
      concentration with diverse bacterial populations and can provide an ideal
      environment for the proliferation of mobile elements such as plasmids. WWTPs have
      also been identified as reservoirs for antibiotic resistance genes that are
      associated with human pathogens. The objectives of this study were to isolate and
      characterize self-transmissible or mobilizable resistance plasmids associated
      with effluent from WWTP. An enrichment culture approach designed to capture
      plasmids conferring resistance to high concentrations of erythromycin was used to
      capture plasmids from an urban WWTP servicing a population of ca. 210,000. DNA
      sequencing of the plasmids revealed diversity of plasmids represented by
      incompatibility groups IncU, col-E, IncFII and IncP-1beta. Genes coding
      resistance to clinically relevant antibiotics (macrolide, tetracycline, beta
      lactam, trimethoprim, chloramphenicol, sulphonamide), quaternary ammonium
      compounds and heavy metals were co-located on these plasmids, often within
      transposable and integrative mobile elements. Several of the plasmids were self
      transmissible or mobilizable and could be maintained in the absence of antibiotic
      selection. The IncFII plasmid pEFC36a showed the highest degree of sequence
      identity to plasmid R1 which has been isolated in England more than 50 years ago
      from a patient suffering from a Salmonella infection. Functional conservation of
      key regulatory features of this F-like conjugation module were demonstrated by
      the finding that the conjugation frequency of pEFC36a could be stimulated by the
      positive regulator of plasmid R1 DNA transfer genes, TraJ. 

PMID- 25389418
TI  - Bacterial programming of host responses: coordination between type I interferon
      and cell death.
AB  - During mammalian infection, bacteria induce cell death from an extracellular or
      intracellular niche that can protect or hurt the host. Data is accumulating that
      associate type I interferon (IFN) signaling activated by intracellular bacteria
      with programmed death of immune effector cells and enhanced virulence. Multiple
      pathways leading to IFN-dependent host cell death have been described, and in
      some cases it is becoming clear how these mechanisms contribute to virulence. Yet
      common mechanisms of IFN-enhanced bacterial pathogenesis are not obvious and no
      specific interferon stimulated genes have yet been identified that cause
      sensitivity to pathogen-induced cell death. In this review, we will summarize
      some bacterial infections caused by facultative intracellular pathogens and what
      is known about how type I IFN signaling may promote the replication of
      extracellular bacteria rather than stimulate protection. Each of these pathogens
      can survive phagocytosis but their intracellular life cycles are very different,
      they express distinct virulence factors and trigger different pathways of immune
      activation and crosstalk. These differences likely lead to widely varying amounts
      of type I IFN expression and a different inflammatory environment, but these may
      not be important to the pathologic effects on the host. Instead, each pathogen
      induces programmed cell death of key immune cells that have been sensitized by
      the activation of the type I IFN response. We will discuss how IFN-dependent host
      cell death may increase host susceptibility and try to understand common pathways
      of pathogenesis that lead to IFN-enhanced bacterial virulence. 

PMID- 25389420
TI  - Temporal changes in the diazotrophic bacterial communities associated with
      Caribbean sponges Ircinia stroblina and Mycale laxissima.
AB  - Sponges that harbor microalgal or, cyanobacterial symbionts may benefit from
      photosynthetically derived carbohydrates, which are rich in carbon but devoid of
      nitrogen, and may therefore encounter nitrogen limitation. Diazotrophic
      communities associated with two Caribbean sponges, Ircinia strobilina and Mycale
      laxissima were studied in a time series during which three individuals of each
      sponge were collected in four time points (5:00 AM, 12:00 noon, 5:00 PM, 10:00
      PM). nifH genes were successfully amplified from the corresponding gDNA and cDNA
      pools and sequenced by high throughput 454 amplicon sequencing. In both sponges,
      over half the nifH transcripts were classified as from cyanobacteria and the
      remainder from heterotrophic bacteria. We found various groups of bacteria
      actively expressing the nifH gene during the entire day-night cycle, an
      indication that the nitrogen fixation potential was fully exploited by different
      nitrogen fixing bacteria groups associated with their hosts. This study showed
      for the first time the dynamic changes in the activity of the diazotrophic
      bacterial communities in marine sponges. Our study expands understanding of the
      diazotrophic groups that contribute to the fixed nitrogen pool in the benthic
      community. Sponge bacterial community-associated diazotrophy may have an
      important impact on the nitrogen biogeochemical cycle in the coral reef
      ecosystem. 

PMID- 25389421
TI  - Impact of interspecific interactions on antimicrobial activity among soil
      bacteria.
AB  - Certain bacterial species produce antimicrobial compounds only in the presence of
      a competing species. However, little is known on the frequency of interaction
      mediated induction of antibiotic compound production in natural communities of
      soil bacteria. Here we developed a high-throughput method to screen for the
      production of antimicrobial activity by monocultures and pair-wise combinations
      of 146 phylogenetically different bacteria isolated from similar soil habitats.
      Growth responses of two human pathogenic model organisms, Escherichia coli WA321
      and Staphylococcus aureus 533R4, were used to monitor antimicrobial activity.
      From all isolates, 33% showed antimicrobial activity only in monoculture and 42%
      showed activity only when tested in interactions. More bacterial isolates were
      active against S. aureus than against E. coli. The frequency of interaction
      mediated induction of antimicrobial activity was 6% (154 interactions out of
      2798) indicating that only a limited set of species combinations showed such
      activity. The screening revealed also interaction-mediated suppression of
      antimicrobial activity for 22% of all combinations tested. Whereas all patterns
      of antimicrobial activity (non-induced production, induced production and
      suppression) were seen for various bacterial classes, interaction-mediated
      induction of antimicrobial activity was more frequent for combinations of
      Flavobacteria and alpha- Proteobacteria. The results of our study give a first
      indication on the frequency of interference competitive interactions in natural
      soil bacterial communities which may forms a basis for selection of bacterial
      groups that are promising for the discovery of novel, cryptic antibiotics. 

PMID- 25389422
TI  - Physico-chemical and microbiological characterization of spontaneous fermentation
      of Cellina di Nardo and Leccino table olives.
AB  - Table olives are one of the most important traditional fermented vegetables in
      Europe and their world consumption is constantly increasing. In the Greek style,
      table olives are obtained by spontaneous fermentations, without any chemical
      debittering treatment. Evolution of sugars, organic acids, alcohols, mono, and
      polyphenol compounds and volatile compounds associated with the fermentative
      metabolism of yeasts and bacteria throughout the natural fermentation process of
      the two Italian olive cultivars Cellina di Nardo and Leccino were determined. A
      protocol was developed and applied aimed at the technological characterization of
      lactic acid bacteria (LAB) and yeast strains as possible candidate autochthonous
      starters for table olive fermentation from Cellina di Nardo and Leccino
      cultivars. The study of the main physic-chemical parameters and volatile
      compounds during fermentation helped to determine chemical descriptors that may
      be suitable for monitoring olive fermentation. In both the analyzed table olive
      cultivars, aldehydes proved to be closely related to the first stage of
      fermentation (30 days), while higher alcohols (2-methyl-1-propanol; 3-methyl-1
      butanol), styrene, and o-cymene were associated with the middle stage of
      fermentation (90 days) and acetate esters with the final step of olive
      fermentation (180 days). 

PMID- 25389423
TI  - Modeling adaptation of carbon use efficiency in microbial communities.
AB  - In new microbial-biogeochemical models, microbial carbon use efficiency (CUE) is
      often assumed to decline with increasing temperature. Under this assumption, soil
      carbon losses under warming are small because microbial biomass declines. Yet
      there is also empirical evidence that CUE may adapt (i.e., become less sensitive)
      to warming, thereby mitigating negative effects on microbial biomass. To analyze
      potential mechanisms of CUE adaptation, I used two theoretical models to
      implement a tradeoff between microbial uptake rate and CUE. This rate-yield
      tradeoff is based on thermodynamic principles and suggests that microbes with
      greater investment in resource acquisition should have lower CUE. Microbial
      communities or individuals could adapt to warming by reducing investment in
      enzymes and uptake machinery. Consistent with this idea, a simple analytical
      model predicted that adaptation can offset 50% of the warming-induced decline in
      CUE. To assess the ecosystem implications of the rate-yield tradeoff, I
      quantified CUE adaptation in a spatially-structured simulation model with 100
      microbial taxa and 12 soil carbon substrates. This model predicted much lower CUE
      adaptation, likely due to additional physiological and ecological constraints on
      microbes. In particular, specific resource acquisition traits are needed to
      maintain stoichiometric balance, and taxa with high CUE and low enzyme investment
      rely on low-yield, high-enzyme neighbors to catalyze substrate degradation. In
      contrast to published microbial models, simulations with greater CUE adaptation
      also showed greater carbon storage under warming. This pattern occurred because
      microbial communities with stronger CUE adaptation produced fewer degradative
      enzymes, despite increases in biomass. Thus, the rate-yield tradeoff prevents CUE
      adaptation from driving ecosystem carbon loss under climate warming. 

PMID- 25389424
TI  - In vitro Studies of the Antibody Response: Antibodies of Different Specificity
      are Made in Different Populations of Cells.

PMID- 25389425
TI  - Classical and Alternative Activation and Metalloproteinase Expression Occurs in
      Foam Cell Macrophages in Male and Female ApoE Null Mice in the Absence of T and B
      Lymphocytes.
AB  - BACKGROUND: Rupture of advanced atherosclerotic plaques accounts for most life
      threatening myocardial infarctions. Classical (M1) and alternative (M2)
      macrophage activation could promote atherosclerotic plaque progression and
      rupture by increasing production of proteases, including matrix
      metalloproteinases (MMPs). Lymphocyte-derived cytokines may be essential for
      generating M1 and M2 phenotypes in plaques, although this has not been rigorously
      tested until now. METHODS AND RESULTS: We validated the expression of M1 markers
      (iNOS and COX-2) and M2 markers (arginase-1, Ym-1, and CD206) and then measured
      MMP mRNA levels in mouse macrophages during classical and alternative activation
      in vitro. We then compared mRNA expression of these genes ex vivo in foam cells
      from subcutaneous granulomas in fat-fed immune-competent ApoE knockout (KO) and
      immune-compromised ApoE/Rag-1 double-KO mice, which lack all T and B cells.
      Furthermore, we performed immunohistochemistry in subcutaneous granulomas and in
      aortic root and brachiocephalic artery atherosclerotic plaques to measure the
      extent of M1/M2 marker and MMP protein expression in vivo. Classical activation
      of mouse macrophages with bacterial lipopolysaccharide in vitro increased MMPs
      13, -14, and -25 but decreased MMP-19 and TIMP-2 mRNA expressions. Alternative
      activation with IL-4 increased MMP-19 expression. Foam cells in subcutaneous
      granulomas expressed all M1/M2 markers and MMPs at ex vivo mRNA and in vivo
      protein levels, irrespective of Rag-1 genotype. There were also similar
      percentages of foam cell macrophages (FCMs) carrying M1/M2 markers and MMPs in
      atherosclerotic plaques from ApoE KO and ApoE/Rag-1 double-KO mice. CONCLUSION:
      Classical and alternative activation leads to distinct MMP expression patterns in
      mouse macrophages in vitro. M1 and M2 polarization in vivo occurs in the absence
      of T and B lymphocytes in either granuloma or plaque FCMs.

PMID- 25389426
TI  - Frequency Patterns of T-Cell Exposed Amino Acid Motifs in Immunoglobulin Heavy
      Chain Peptides Presented by MHCs.
AB  - Immunoglobulins are highly diverse protein sequences that are processed and
      presented to T-cells by B-cells and other antigen presenting cells. We examined a
      large dataset of immunoglobulin heavy chain variable regions (IGHV) to assess the
      diversity of T-cell exposed motifs (TCEMs). TCEM comprise those amino acids in a
      MHC-bound peptide, which face outwards, surrounded by the MHC histotope, and
      which engage the T-cell receptor. Within IGHV there is a distinct pattern of
      predicted MHC class II binding and a very high frequency of re-use of the TCEMs.
      The re-use frequency indicates that only a limited number of different cognate T
      cells are required to engage many different clonal B-cells. The amino acids in
      each outward-facing TCEM are intercalated with the amino acids of inward-facing
      MHC groove-exposed motifs (GEM). Different GEM may have differing, allele
      specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide
      allows for a vast combinatorial repertoire of epitopes, each eliciting a
      different response. Outcome of T-cell receptor binding is determined by overall
      signal strength, which is a function of the number of responding T-cells and the
      duration of engagement. Hence, the frequency of TCEM re-use appears to be an
      important determinant of whether a T-cell response is stimulatory or suppressive.
      The frequency distribution of TCEMs implies that somatic hypermutation is
      followed by T-cell clonal expansion that develops along repeated pathways. The
      observations of TCEM and GEM derived from immunoglobulins suggest a relatively
      simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re
      use of TCEMs, with a very high degree of specificity achieved by combination with
      a diversity of GEMs. The frequency profile of TCEMs also points to an economical
      mechanism for maintaining T-cell memory, recall, and self-discrimination based on
      an endogenously generated profile of motifs. 

PMID- 25389429
TI  - Protein encoded by oncogene 6b from Agrobacterium tumefaciens has a reprogramming
      potential and histone chaperone-like activity.
AB  - Crown gall tumors are formed mainly by actions of a group of genes in the T-DNA
      that is transferred from Agrobacterium tumefaciens and integrated into the
      nuclear DNA of host plants. These genes encode enzymes for biosynthesis of auxin
      and cytokinin in plant cells. Gene 6b in the T-DNA affects tumor morphology and
      this gene alone is able to induce small tumors on certain plant species. In
      addition, unorganized calli are induced from leaf disks of tobacco that are
      incubated on phytohormone-free media; shooty teratomas, and morphologically
      abnormal plants, which might be due to enhanced competence of cell division and
      meristematic states, are regenerated from the calli. Thus, the 6b gene appears to
      stimulate a reprogramming process in plants. To uncover mechanisms behind this
      process, various approaches including the yeast-two-hybrid system have been
      exploited and histone H3 was identified as one of the proteins that interact with
      6b. It has been also demonstrated that 6b acts as a histone H3 chaperon in vitro
      and affects the expression of various genes related to cell division competence
      and the maintenance of meristematic states. We discuss current views on a role of
      6b protein in tumorigenesis and reprogramming in plants. 

PMID- 25389427
TI  - NKT cell networks in the regulation of tumor immunity.
AB  - CD1d-restricted natural killer T (NKT) cells lie at the interface between the
      innate and adaptive immune systems and are important mediators of immune
      responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid
      antigens, and their rapid yet specific reactions influence both innate and
      adaptive immunity. In tumor immunity, two NKT subsets (type I and type II) have
      contrasting roles in which they not only cross-regulate one another, but also
      impact innate immune cell populations, including natural killer, dendritic, and
      myeloid lineage cells, as well as adaptive populations, especially CD8(+) and
      CD4(+) T cells. The extent to which NKT cells promote or suppress surrounding
      cells affects the host's ability to prevent neoplasia and is consequently of
      great interest for therapeutic development. Data have shown the potential for
      therapeutic use of NKT cell agonists and synergy with immune response modifiers
      in both pre-clinical studies and preliminary clinical studies. However, there is
      room to improve treatment efficacy by further elucidating the biological
      mechanisms underlying NKT cell networks. Here, we discuss the progress made in
      understanding NKT cell networks, their consequent role in the regulation of tumor
      immunity, and the potential to exploit that knowledge in a clinical setting. 

PMID- 25389430
TI  - The bud break process and its variation among local populations of boreal black
      spruce.
AB  - Phenology of local populations can exhibit adaptations to the current
      environmental conditions resulting from a close interaction between climate and
      genotype. The bud break process and its variations among populations were
      analyzed in greenhouse by monitoring the growth resumption in black spruce [Picea
      mariana (Mill.) BSP] seedlings originating from seeds of five stands across the
      closed boreal forest in Quebec, Canada. Bud break lasted 15 days and occurred
      earlier and quicker in northern provenances. Provenance explained between 10.2
      and 32.3% of the variance in bud break, while the families accounted for a
      smaller but still significant part of the variance. The late occurrence of one
      phenological phase corresponded to a delayed occurrence of the others according
      to linear relationships. A causal model was proposed in the form of a chain of
      events with each phase of bud break being related to the previous and successive
      one, while no link was observed between non-adjacent phases. The adaptation of
      black spruce populations along the latitudinal gradient points toward a strategy
      based on rapid physiological processes triggered by temperature increase inducing
      high metabolic activity. The variation observed in bud break reflects an
      evolutionary trade-off between maximization of security and taking advantage of
      the short growing season. This work provides evidence of the phenological
      adaptations of black spruce to its local environmental conditions while retaining
      sizeable genetic diversity within populations. Because of the multigenic nature
      of phenology, this diversity should provide some raw material for adaptation to
      changing local environmental conditions. 

PMID- 25389428
TI  - Light and gravity signals synergize in modulating plant development.
AB  - Tropisms are growth-mediated plant movements that help plants to respond to
      changes in environmental stimuli. The availability of water and light, as well as
      the presence of a constant gravity vector, are all environmental stimuli that
      plants sense and respond to via directed growth movements (tropisms). The plant
      response to gravity (gravitropism) and the response to unidirectional light
      (phototropism) have long been shown to be interconnected growth phenomena. Here,
      we discuss the similarities in these two processes, as well as the known
      molecular mechanisms behind the tropistic responses. We also highlight research
      done in a microgravity environment in order to decouple two tropisms through
      experiments carried out in the absence of a significant unilateral gravity
      vector. In addition, alteration of gravity, especially the microgravity
      environment, and light irradiation produce important effects on meristematic
      cells, the undifferentiated, highly proliferating, totipotent cells which sustain
      plant development. Microgravity produces the disruption of meristematic
      competence, i.e., the decoupling of cell proliferation and cell growth, affecting
      the regulation of the cell cycle and ribosome biogenesis. Light irradiation,
      especially red light, mediated by phytochromes, has an activating effect on these
      processes. Phytohormones, particularly auxin, also are key mediators in these
      alterations. Upcoming experiments on the International Space Station will clarify
      some of the mechanisms and molecular players of the plant responses to these
      environmental signals involved in tropisms and the cell cycle. 

PMID- 25389431
TI  - Novel insights from non-conserved microRNAs in plants.
AB  - Plant microRNAs (miRNAs), a class of small non-coding regulatory RNAs, are
      canonically 20-24 nucleotides in length and bind to complementary target RNA
      sequences, guiding target attenuation via mRNA degradation or translation
      inhibition. Of the annotated miRNA families, evolutionarily conserved families
      have been well known to extensively regulate analogous targets and play critical
      roles in plant development and adaptation to adverse environments. By contrast,
      majority of these families that are merely present in a specific lineage or in a
      few closely related species have not been well functionally explored until
      recently. The fast-growing progresses being made in the actions of non-conserved
      miRNAs nowadays in diverse plant species may represent a highly promising
      research field in future. This review thereby summarizes the emerging advances in
      our understanding of the biogenesis, associated effectors, modes to targets, and
      biological functions of plant non-conserved miRNAs. In addition, it outlines the
      regulatory units recently discovered between conserved miRNAs and their
      alternative targets. 

PMID- 25389432
TI  - Epigenetic modulation in the treatment of atherosclerotic disease.
AB  - Cardiovascular disease is the single largest cause of death in the western world
      and its incidence is on the rise globally. Atherosclerosis, characterized by the
      development of atheromatus plaque, can trigger luminal narrowing and upon rupture
      result in myocardial infarction or ischemic stroke. Epigenetic phenomena are a
      focus of considerable research interest due to the role they play in gene
      regulation. Epigenetic mechanisms such as DNA methylation and histone acetylation
      have been identified as potential drug targets in the treatment of cardiovascular
      disease. miRNAs are known to play a role in gene silencing, which has been widely
      investigated in cancer. In comparison, the role they play in cardiovascular
      disease and plaque rupture is not well understood. Nutritional epigenetic
      modifiers from dietary components, for instance sulforaphane found in broccoli,
      have been shown to suppress the pro-inflammatory response through transcription
      factor activation. This review will discuss current and potential epigenetic
      therapeutics for the treatment of cardiovascular disease, focusing on the use of
      miRNAs and dietary supplements such as sulforaphane and protocatechuic aldehyde. 

PMID- 25389433
TI  - Identification of rare variants in Alzheimer's disease.
AB  - Much progress has been made in recent years in identifying genes involved in the
      risk of developing Alzheimer's disease (AD), the most common form of dementia.
      Yet despite the identification of over 20 disease associated loci, mainly through
      genome wide association studies (GWAS), a large proportion of the genetic
      component of the disorder remains unexplained. Recent evidence from the AD field,
      as with other complex diseases, suggests a large proportion of this "missing
      heritability" may be due to rare variants of moderate to large effect size, but
      the methodologies to detect such variants are still in their infancy. The latest
      studies in the field have been focused on the identification of coding variation
      associated with AD risk, through whole-exome or whole-genome sequencing. Such
      variants are expected to have larger effect sizes than GWAS loci, and are easier
      to functionally characterize, and develop cellular and animal models for. This
      review explores the issues involved in detecting rare variant associations in the
      context of AD, highlighting some successful approaches utilized to date. 

PMID- 25389434
TI  - High throughput sample processing and automated scoring.
AB  - The comet assay is a sensitive and versatile method for assessing DNA damage in
      cells. In the traditional version of the assay, there are many manual steps
      involved and few samples can be treated in one experiment. High throughput (HT)
      modifications have been developed during recent years, and they are reviewed and
      discussed. These modifications include accelerated scoring of comets; other
      important elements that have been studied and adapted to HT are cultivation and
      manipulation of cells or tissues before and after exposure, and freezing of
      treated samples until comet analysis and scoring. HT methods save time and money
      but they are useful also for other reasons: large-scale experiments may be
      performed which are otherwise not practicable (e.g., analysis of many organs from
      exposed animals, and human biomonitoring studies), and automation gives more
      uniform sample treatment and less dependence on operator performance. The HT
      modifications now available vary largely in their versatility, capacity,
      complexity, and costs. The bottleneck for further increase of throughput appears
      to be the scoring. 

PMID- 25389436
TI  - The effects of baclofen for the treatment of gastroesophageal reflux disease: a
      meta-analysis of randomized controlled trials.
AB  - Objectives. Baclofen can relieve gastroesophageal reflux-related symptoms in
      healthy subjects and gastroesophageal reflux disease (GERD) patients by reducing
      the incidence of transient lower esophageal sphincter relaxation. This meta
      analysis aimed to evaluate the efficacy and safety of baclofen for the treatment
      of GERD. Methods. We systematically searched randomized controlled trials
      published prior to November 2013 from PubMed, Medline, Embase, ScienceDirect,
      ClinicalTrials.gov, and the Cochrane Central Register of Randomized Controlled
      Trials. We performed a meta-analysis of all eligible trials. Results. Nine
      studies were identified with a total of 283 GERD patients and healthy subjects.
      Comparative analysis provided high quality data supporting the ability of
      baclofen to promote a short-term decrease in the number of reflux episodes per
      patient, the average length of reflux episodes, and the incidence of transient
      lower esophageal sphincter relaxation. No serious adverse events or death events
      were reported, and there were no significant differences in the overall adverse
      events between baclofen and placebo. All reported side effects of baclofen were
      of mild-to-moderate intensity, and the drug was well tolerated. Conclusion.
      Abundant evidence suggests that baclofen may be a useful approach for the
      treatment of GERD patients; however, a larger well-designed research study would
      further confirm this recommendation. 

PMID- 25389435
TI  - How does evolution tune biological noise?
AB  - Part of molecular and phenotypic differences between individual cells, between
      body parts, or between individuals can result from biological noise. This source
      of variation is becoming more and more apparent thanks to the recent advances in
      dynamic imaging and single-cell analysis. Some of these studies showed that the
      link between genotype and phenotype is not strictly deterministic. Mutations can
      change various statistical properties of a biochemical reaction, and thereby the
      probability of a trait outcome. The fact that they can modulate phenotypic noise
      brings up an intriguing question: how may selection act on these mutations? In
      this review, we approach this question by first covering the evidence that
      biological noise is under genetic control and therefore a substrate for
      evolution. We then sequentially inspect the possibilities of negative, neutral,
      and positive selection for mutations increasing biological noise. Finally, we
      hypothesize on the specific case of H2A.Z, which was shown to both buffer
      phenotypic noise and modulate transcriptional efficiency. 

PMID- 25389437
TI  - Report of a Novel Mutation in MLH1 Gene in a Hispanic Family from Puerto Rico
      Fulfilling Classic Amsterdam Criteria for Lynch Syndrome.
AB  - In Puerto Rico, colorectal cancer (CRC) represents the second leading cause of
      cancer in men and women. Familial CRC accounts for 10-15% of the total CRC cases,
      while Lynch syndrome accounts for approximately 2-4% of cases. Limited
      information is available about the prevalence, clinical manifestations, and
      genetic mutations of hereditary CRC in US Hispanic individuals. In this paper we
      report a novel mutation in the hMLH1 gene in a Puerto Rican Hispanic family with
      Lynch syndrome recruited through the Puerto Rico Familial Colorectal Cancer
      Registry (PURIFICAR). Our proband was identified by applying Amsterdam and
      Bethesda criteria for Lynch syndrome, analysis of protein expression by
      immunohistochemistry, and genetic sequencing of the mismatch repair genes. A
      novel mutation at c.2044_2045 in hMLH1 consisting of the deletion of two
      consecutive nucleotides (AT) at exon 18 was identified. This deletion causes a
      frameshift in the protein coding sequence at p.682 resulting in premature
      termination and a truncated MLH1 protein. To our knowledge, this mutation has not
      been previously reported in the literature. The detection of this novel mutation
      in MLH1 further emphasizes the need for genetic testing in at-risk patients for
      hereditary CRC from various ethnic and racial backgrounds. 

PMID- 25389438
TI  - The Effects of Lycopene on the Methylation of the GSTP1 Promoter and Global
      Methylation in Prostatic Cancer Cell Lines PC3 and LNCaP.
AB  - DNA (cytosine-5-) methylation silencing of GSTP1 function occurs in prostate
      adenocarcinoma (PCa). Previous studies have shown that there is an inverse
      relationship between dietary lycopene intake and the risk of PCa. However, it is
      unknown whether lycopene reactivates the tumor suppressor gene glutathioneS
      transferase-pi (GSTP1) by demethylation of the hypermethylated CpGs that act to
      silence the GSTP1 promoter. Here, we demonstrated that lycopene treatment
      significantly decreased the methylation levels of the GSTP1 promoter and
      increased the mRNA and protein levels of GSTP1 in an androgen-independent PC-3
      cell line. In contrast, lycopene treatment did not demethylate the GSTP1 promoter
      or increase GSTP1 expression in the androgen-dependent LNCaP cell line. DNA
      methyltransferase (DNMT) 3A protein levels were downregulated in PC-3 cells
      following lycopene treatment; however, DNMT1 and DNMT3B levels were unchanged.
      Furthermore, the long interspersed element (LINE-1) and short interspersed
      element ALU were not demethylated when treated by lycopene. In LNCaP cells,
      lycopene treatment did not affect any detected DNMT protein expression, and the
      methylation levels of LINE-1 and ALU were decreased. These results indicated that
      the protective effect of lycopene on the prostate is different between androgen
      dependent and androgen-independent derived PCa cells. Further, in vivo studies
      should be conducted to confirm these promising results and to evaluate the
      potential role of lycopene in the protection of the prostate. 

PMID- 25389439
TI  - Pattern of Blood Stream Infections within Neonatal Intensive Care Unit, Suez
      Canal University Hospital, Ismailia, Egypt.
AB  - Introduction. Blood stream infection (BSI) is a common problem of newborn in
      neonatal intensive care units (NICUs). Monitoring neonatal infections is
      increasingly regarded as an important contributor to safe and high-quality
      healthcare. It results in high mortality rate and serious complications. So, our
      aim was to determine the incidence and the pattern of BSIs in the NICU of Suez
      Canal University Hospital, Egypt, and to determine its impact on hospitalization,
      mortality, and morbidity. Methods. This study was a prospective one in which all
      neonates admitted to the NICUs in Suez Canal University hospital between January,
      2013 and June 2013 were enrolled. Blood stream infections were monitored
      prospectively. The health care associated infection rate, mortality rate,
      causative organism, and risk factors were studied. Results. A total of 317
      neonates were admitted to the NICU with a mortality rate of 36.0%. During this
      study period, 115/317 (36.3%) developed clinical signs of sepsis and were
      confirmed as BSIs by blood culture in only 90 neonates with 97 isolates. The
      total mean length of stay was significantly longer among infected than
      noninfected neonates (34.5 +/- 18.3 and 10.8 +/- 9.9 days, resp., P value <
      0.001). The overall mortality rates among infected and noninfected neonates were
      38.9% and 34.8%, respectively, with a significant difference. Klebsiella spp.
      were the most common pathogen (27.8%) followed by Pseudomonas (21.6%) and
      Staphylococcus aureus (15.4%). Conclusion. The rate of BSIs in NICU at Suez Canal
      University Hospital was relatively high with high mortality rate (36.0%). 

PMID- 25389440
TI  - Blastocystis and schistosomiasis coinfection in a patient with chronic kidney
      disease.
AB  - Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent a
      spectrum of impaired immunity with effects on cellular immunity, soluble immune
      factors, and inflammation. As a result, infections due to impaired immune system
      responses are responsible for significant morbidity in patients with kidney
      disease. Because of immune dysfunction in CKD, these patients have reduced
      probability to clear infections and are susceptible to pathogenic effects of
      common organisms. We present a case of a patient with CKD coinfected with
      Schistosoma mansoni and Blastocystis spp. This appears to be the first reported
      association of Schistosoma mansoni and Blastocystis spp. in a patient with CKD. 

PMID- 25389441
TI  - Akebia trifoliate (Thunb.) Koidz Seed Extract Inhibits the Proliferation of Human
      Hepatocellular Carcinoma Cell Lines via Inducing Endoplasmic Reticulum Stress.
AB  - Akebia Fructus has long been used for hepatocellular carcinoma (HCC) in China,
      while the molecular mechanism remains obscure. Our recent work found that Akebia
      trifoliate (Thunb.) Koidz seed extract (ATSE) suppressed proliferation and
      induced endoplasmic reticulum (ER) stress in SMMC-7721. The present study aimed
      to throw more light on the mechanism. ER stress occurred after ATSE treatment in
      HepG2, HuH7, and SMMC-7721 cells, manifested as ER expansion, and SMMC-7721 was
      the most sensitive kind in terms of morphology. Cell viability assay showed that
      ATSE significantly inhibited cells proliferation. Flow cytometry analysis
      indicated that ATSE leads to an upward tendency of G0/G1 phase and a reduced
      trend of the continuous peak after G2/M phase in HepG2; ATSE promoted apoptosis
      in HuH7 and a notable reduction in G0/G1 phase; ATSE does not quite influence
      cell cycles of SMMC-7721. Western blot analysis showed an increased trend of the
      chosen ER stress-related proteins after different treatments but
      nonsignificantly; only HYOU1 and GRP78 were decreased notably by ATSE in HuH7.
      Affymetrix array indicated that lots of ER stress-related genes' expressions were
      significantly altered, and downward is the main trend. These results suggest that
      ATSE have anticancer potency in HCC cells via partly inducing ER stress. 

PMID- 25389442
TI  - Yiqi formula enhances the antitumor effects of erlotinib for treatment of triple
      negative breast cancer xenografts.
AB  - Yiqi formula (YF), a traditional herbal prescription, has long been used to treat
      triple-negative breast cancer (TNBC) patients. The present study aims to
      investigate the effects and the related mechanism of YF for treatment of TNBC
      xenografts. MDA-MB-231 (human TNBC) cells were subcutaneously injected into the
      second mammary fat pad of 40 female nude mice, which were divided into four
      groups: control, erlotinib (an epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor), YF, and combination (YF plus erlotinib). All treatments were
      administered orally for 30 days. Inhibition rate of tumor weight by erlotinib,
      YF, and the combination was 26.47%, 17.24%, and 39.15%, respectively. Western
      blotting showed that YF, erlotinib, and the combination downregulated p-EGFR (P <
      0.01) and p-Akt1 (pT308) (P < 0.05) and upregulated PTEN compared with control,
      and the combination was more efficacious than erlotinib alone (P < 0.05). Similar
      results were detected by immunohistochemistry. Real-time quantitative PCR showed
      that YF, erlotinib, and the combination increased PTEN mRNA (P < 0.05, P < 0.01)
      compared with control, and the combination was more efficacious than erlotinib
      alone (P < 0.05). In conclusion, YF can regulate the main components of the
      PI3K/Akt pathway in TNBC xenografts. When YF was used in combination with
      erlotinib, it enhanced the antitumor effects of erlotinib on TNBC xenografts.
      These findings suggest that YF is suitable to use for the treatment of TNBC
      patients. 

PMID- 25389443
TI  - Proof-of-Concept Randomized Controlled Study of Cognition Effects of the
      Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4
      in Cognitively Healthy Subjects: Implications for Alzheimer's Dementia.
AB  - Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype
      4) plays a crucial role in regulating cognition via the PDE-4-cAMP cascade
      signaling involving phosphorylated cAMP response element binding protein (CREB).
      Objective. The primary endpoint was to examine the neurocognitive effects of
      extract Sceletium tortuosum (Zembrin) and to assess the safety and tolerability
      of Zembrin in cognitively healthy control subjects. Method. We chose the
      randomized double-blind placebo-controlled cross-over design in our study. We
      randomized normal healthy subjects (total n = 21) to receive either 25 mg capsule
      Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo
      controlled 3-week cross-over design. We administered battery of
      neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale
      (HAM-D) at baseline and regular intervals and monitored side effects with
      treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6
      years +/- 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25 mg
      daily dosage significantly improved cognitive set flexibility (P < 0.032) and
      executive function (P < 0.022), compared with the placebo group. Positive changes
      in mood and sleep were found. Zembrin was well tolerated. Conclusion. The
      promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP
      CREB cascade, a novel drug target in the potential treatment of early Alzheimer's
      dementia. This trial is registered with ClinicalTrials.gov NCT01805518. 

PMID- 25389444
TI  - Unveiling the factors shaping the distribution of widely distributed alpine
      vertebrates, using multi-scale ecological niche modelling of the bat Plecotus
      macrobullaris.
AB  - Several alpine vertebrates share a distribution pattern that extends across the
      South-western Palearctic but is limited to the main mountain massifs. Although
      they are usually regarded as cold-adapted species, the range of many alpine
      vertebrates also includes relatively warm areas, suggesting that factors beyond
      climatic conditions may be driving their distribution. In this work we first
      recognize the species belonging to the mentioned biogeographic group and, based
      on the environmental niche analysis of Plecotus macrobullaris, we identify and
      characterize the environmental factors constraining their ranges. Distribution
      overlap analysis of 504 European vertebrates was done using the Sorensen
      Similarity Index, and we identified four birds and one mammal that share the
      distribution with P. macrobullaris. We generated 135 environmental niche models
      including different variable combinations and regularization values for P.
      macrobullaris at two different scales and resolutions. After selecting the best
      models, we observed that topographic variables outperformed climatic predictors,
      and the abruptness of the landscape showed better predictive ability than
      elevation. The best explanatory climatic variable was mean summer temperature,
      which showed that P. macrobullaris is able to cope with mean temperature ranges
      spanning up to 16 degrees C. The models showed that the distribution of P.
      macrobullaris is mainly shaped by topographic factors that provide rock-abundant
      and open-space habitats rather than climatic determinants, and that the species
      is not a cold-adapted, but rather a cold-tolerant eurithermic organism. P.
      macrobullaris shares its distribution pattern as well as several ecological
      features with five other alpine vertebrates, suggesting that the conclusions
      obtained from this study might be extensible to them. We concluded that rock
      dwelling and open-space foraging vertebrates with broad temperature tolerance are
      the best candidates to show wide alpine distribution in the Western Palearctic. 

PMID- 25389445
TI  - Differentiated adaptive evolution, episodic relaxation of selective constraints,
      and pseudogenization of umami and sweet taste genes TAS1Rs in catarrhine
      primates.
AB  - BACKGROUND: Umami and sweet tastes are two important basic taste perceptions that
      allow animals to recognize diets with nutritious carbohydrates and proteins,
      respectively. Until recently, analyses of umami and sweet taste were performed on
      various domestic and wild animals. While most of these studies focused on the
      pseudogenization of taste genes, which occur mostly in carnivores and species
      with absolute feeding specialization, omnivores and herbivores were more or less
      neglected. Catarrhine primates are a group of herbivorous animals (feeding mostly
      on plants) with significant divergence in dietary preference, especially the
      specialized folivorous Colobinae. Here, we conducted the most comprehensive
      investigation to date of selection pressure on sweet and umami taste genes
      (TAS1Rs) in catarrhine primates to test whether specific adaptive evolution
      occurred during their diversification, in association with particular plant
      diets. RESULTS: We documented significant relaxation of selective constraints on
      sweet taste gene TAS1R2 in the ancestral branch of Colobinae, which might
      correlate with their unique ingestion and digestion of leaves. Additionally, we
      identified positive selection acting on Cercopithecidae lineages for the umami
      taste gene TAS1R1, on the Cercopithecinae and extant Colobinae and Hylobatidae
      lineages for TAS1R2, and on Macaca lineages for TAS1R3. Our research further
      identified several site mutations in Cercopithecidae, Colobinae and Pygathrix,
      which were detected by previous studies altering the sensitivity of receptors.
      The positively selected sites were located mostly on the extra-cellular region of
      TAS1Rs. Among these positively selected sites, two vital sites for TAS1R1 and
      four vital sites for TAS1R2 in extra-cellular region were identified as being
      responsible for the binding of certain sweet and umami taste molecules through
      molecular modelling and docking. CONCLUSIONS: Our results suggest that episodic
      and differentiated adaptive evolution of TAS1Rs pervasively occurred in
      catarrhine primates, most concentrated upon the extra-cellular region of TAS1Rs.

PMID- 25389446
TI  - Engagement in assertive community treatment as experienced by recovering clients
      with severe mental illness and concurrent substance use.
AB  - BACKGROUND: Clients with severe mental illness (SMI) who use substances are less
      engaged in treatment than those who do not use substances, and assertive
      community treatment (ACT) engages and retains clients with SMI and concurrent
      substance use at a higher rate compared with traditional treatment. This
      qualitative study aimed to explore the experiences of being recruited to, and
      remaining in, ACT among recovering clients diagnosed with SMI and concurrent
      substance use. METHODS: Twenty semi-structured interviews were undertaken among
      11 clients with SMI and concurrent substance use who were included in ACT teams.
      The inclusion criteria were SMI and concurrent substance use and improvement
      after a minimum of 12 months in treatment regarding one or several of the
      following parameters: quality of life, general functioning and substance use.
      Systematic text condensation was applied in the analyses. RESULTS: The
      experiences of building trust through enduring involvement and receiving benefits
      were most important for the acceptance of ACT by clients. A feeling of
      exclusiveness, perceiving ACT as a safety net and the clients' own personal
      responsibility for taking part in the treatment were stated as the most important
      factors for remaining in treatment. CONCLUSIONS: The implications of the results
      of the present study are that service providers have to prove that they can be
      trusted in the initial phase of the clients' contact with the team. The feeling
      by clients with SMI and concurrent substance use that service providers in ACT
      believe they can improve their client's quality of life, is of importance for
      feeling exclusive, having hope for the future and remaining in treatment.

PMID- 25389447
TI  - Current Therapeutic Research is Now Indexed on PubMed.

PMID- 25389448
TI  - Co-encapsulation of Doxorubicin with galactoxyloglucan nanoparticles for
      intracellular tumor-targeted delivery in murine ascites and solid tumors.
AB  - Doxorubicin (Dox) treatment is limited by severe toxicity and frequent episodes
      of treatment failure. To minimize adverse events and improve drug delivery
      efficiently and specifically in cancer cells, encapsulation of Dox with naturally
      obtained galactoxyloglucan polysaccharide (PST001), isolated from Tamarindus
      indica was attempted. Thus formed PST-Dox nanoparticles induced apoptosis and
      exhibited significant cytotoxicity in murine ascites cell lines, Dalton's
      lymphoma ascites and Ehrlich's ascites carcinoma. The mechanism contributing to
      the augmented cytotoxicity of nanoconjugates at lower doses was validated by
      measuring the Dox intracellular uptake in human colon, leukemic and breast cancer
      cell lines. PST-Dox nanoparticles showed rapid internalization of Dox into cancer
      cells within a short period of incubation. Further, in vivo efficacy was tested
      in comparison to the parent counterparts - PST001 and Dox, in ascites and solid
      tumor syngraft mice models. Treatment of ascites tumors with PST-Dox
      nanoparticles significantly reduced the tumor volume, viable tumor cell count,
      and increased survival and percentage life span in the early, established and
      prophylactic phases of the disease. Administration of nanoparticles through
      intratumoral route delivered more robust antitumor response than the
      intraperitoneal route in solid malignancies. Thus, the results indicate that PST
      Dox nanoparticles have greater potential compared to the Dox as targeted drug
      delivery nanocarriers for loco regional cancer chemotherapy applications. 

PMID- 25389449
TI  - c-Kit Expression is Rate-Limiting for Stem Cell Factor-Mediated Disease
      Progression in Adenoid Cystic Carcinoma of the Salivary Glands.
AB  - Adenoid cystic carcinoma (ACC) is an aggressive malignant neoplasm of the
      salivary glands in which c-Kit is overexpressed and activated, although the
      mechanism for this is as yet unclear. We analyzed 27 sporadic ACC tumor specimens
      to examine the biologic and clinical significance of c-Kit activation. Mutational
      analysis revealed expression of wild-type c-Kit in all, eliminating gene mutation
      as a cause of activation. Because stem cell factor (SCF) is c-Kit's sole ligand,
      we analyzed its expression in the tumor cells and their environment.
      Immunohistochemistry revealed its presence in c-Kit-positive tumor cells,
      suggesting an activation of autocrine signaling. We observed a significant
      induction of ERK1/2 in the cells. SCF staining was also found in other types of
      non-cancerous cells adjacent to tumors within salivary glands, including stromal
      fibroblasts, neutrophils, peripheral nerve, skeletal muscle, vascular endothelial
      cells, mucous acinar cells, and intercalated ducts. Quantitative PCR showed that
      the top quartile of c-Kit mRNA expression distinguished ACCs from normal salivary
      tissues and was cross-correlated with short-term poor prognosis. Expression
      levels of SCF and c-Kit were highly correlated in the cases with perineural
      invasion. These observations suggest that c-Kit is potentially activated by
      receptor dimerization upon stimulation by SCF in ACC, and that the highest
      quartile of c-Kit mRNA expression could be a predictor of poor prognosis. Our
      findings may support an avenue for c-Kit-targeted therapy to improve disease
      control in ACC patients harboring the top quartile of c-Kit mRNA expression. 

PMID- 25389450
TI  - The Rac Inhibitor EHop-016 Inhibits Mammary Tumor Growth and Metastasis in a Nude
      Mouse Model.
AB  - Metastatic disease still lacks effective treatments, and remains the primary
      cause of cancer mortality. Therefore, there is a critical need to develop better
      strategies to inhibit metastatic cancer. The Rho family GTPase Rac is an ideal
      target for anti-metastatic cancer therapy, because Rac is a key molecular switch
      that is activated by a myriad of cell surface receptors to promote cancer cell
      migration/invasion and survival. Previously, we reported the design and
      development of EHop-016, a small molecule compound, which inhibits Rac activity
      of metastatic cancer cells with an IC50 of 1 MUM. EHop-016 also inhibits the
      activity of the Rac downstream effector p21-activated kinase (PAK), lamellipodia
      extension, and cell migration in metastatic cancer cells. Herein, we tested the
      efficacy of EHop-016 in a nude mouse model of experimental metastasis, where EHop
      016 administration at 25 mg/kg body weight (BW) significantly reduced mammary fat
      pad tumor growth, metastasis, and angiogenesis. As quantified by UPLC MS/MS, EHop
      016 was detectable in the plasma of nude mice at 17 to 23 ng/ml levels at 12 h
      following intraperitoneal (i.p.) administration of 10 to 25 mg/kg BW EHop-016.
      The EHop-016 mediated inhibition of angiogenesis In Vivo was confirmed by
      immunohistochemistry of excised tumors and by In Vitro tube formation assays of
      endothelial cells. Moreover, EHop-016 affected cell viability by down-regulating
      Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as
      increasing caspase 3/7 activities in metastatic cancer cells. In conclusion, EHop
      016 has potential as an anticancer compound to block cancer progression via
      multiple Rac-directed mechanisms. 

PMID- 25389451
TI  - NCI Workshop Report: Clinical and Computational Requirements for Correlating
      Imaging Phenotypes with Genomics Signatures.
AB  - The National Cancer Institute (NCI) Cancer Imaging Program organized two related
      workshops on June 26-27, 2013, entitled "Correlating Imaging Phenotypes with
      Genomics Signatures Research" and "Scalable Computational Resources as Required
      for Imaging-Genomics Decision Support Systems." The first workshop focused on
      clinical and scientific requirements, exploring our knowledge of phenotypic
      characteristics of cancer biological properties to determine whether the field is
      sufficiently advanced to correlate with imaging phenotypes that underpin genomics
      and clinical outcomes, and exploring new scientific methods to extract phenotypic
      features from medical images and relate them to genomics analyses. The second
      workshop focused on computational methods that explore informatics and
      computational requirements to extract phenotypic features from medical images and
      relate them to genomics analyses and improve the accessibility and speed of
      dissemination of existing NIH resources. These workshops linked clinical and
      scientific requirements of currently known phenotypic and genotypic cancer
      biology characteristics with imaging phenotypes that underpin genomics and
      clinical outcomes. The group generated a set of recommendations to NCI leadership
      and the research community that encourage and support development of the emerging
      radiogenomics research field to address short-and longer-term goals in cancer
      research. 

PMID- 25389452
TI  - Biodistribution and Efficacy Studies of the Proteasome Inhibitor BSc2118 in a
      Mouse Melanoma Model.
AB  - Inhibition of the proteasome offers many therapeutic possibilities in
      inflammation as well as in neoplastic diseases. However, clinical use of
      proteasome inhibitors is limited by the development of resistance or severe side
      effects. In our study we characterized the anti-tumor properties of the novel
      proteasome inhibitor BSc2118. The sensitivity of tumor lines to BSc2118 was
      analyzed in comparison to bortezomib using crystal violet staining in order to
      assess cell viability. The In Vivo distribution of BSc2118 in mouse tissues was
      tracked by a fluorescent-modified form of BSc2118 (BSc2118-FL) and visualized by
      confocal microscopy. Inhibition of the 20S proteasome was monitored both in
      cultured cell lines and in mice, respectively. Finally, safety and efficacy of
      BSc2118 was evaluated in a mouse melanoma model. BSc2118 inhibits proliferation
      of different tumor cell lines with a similar potency as compared with bortezomib.
      Systemic administration of BSc2118 in mice is well tolerated, even when given in
      a dose of 60 mg/kg body weight. After systemic injection of BSc2118 or bortezomib
      similar proteasome inhibition patterns are observed within the murine organs.
      Detection of BSc2118-FL revealed correlation of distribution pattern of BSc2118
      with inhibition of proteasomal activity in cells or mouse tissues. Finally,
      administration of BSc2118 in a mouse melanoma model shows significant local anti
      tumor effects. Concluding, BSc2118 represents a novel low-toxic agent that might
      be alternatively used for known proteasome inhibitors in anti-cancer treatment. 

PMID- 25389453
TI  - The Wilms' Tumor Gene WT1 - 17AA/- KTS Splice Variant Increases Tumorigenic
      Activity Through Up-Regulation of Vascular Endothelial Growth Factor in an In
      Vivo Ovarian Cancer Model.
AB  - The Wilms' tumor 1 gene WT1 encodes a zinc transcription factor involved in a
      variety of cancer-related processes. In this study, we sought to investigate the
      effects of WT1 splice variants on tumorigenic activity and survival in an in vivo
      ovarian cancer model. To this end, we established stable ovarian cancer cell
      lines transduced with lentiviral constructs containing each of the four WT1
      splice variants (- 17AA/- KTS, + 17AA/- KTS, - 17AA/+ KTS, and + 17AA/+ KTS). In
      mice inoculated intraperitoneally with SKOV3ip1 cells expressing WT1 - 17AA/-
      KTS, disseminated tumor weights and production of ascites were significantly
      increased compared with those in mice inoculated with cells expressing the
      control vector. The overall survival in mice inoulated with WT1 - 17AA/- KTS
      expressing cells was significantly shorter than that in mice inoculated with
      control cells (P = .0115). Immunoblot analysis revealed that WT1 - 17AA/- KTS
      significantly increased the expression of vascular endothelial growth factor
      (VEGF) compared with the control. Greater numbers of CD31-immunopositive vessels
      were observed in tumors from mice injected with cells expressing WT1 - 17AA/- KTS
      than in tumors from control mice. Finally, WT1 - 17AA/- KTS significantly
      increased tumor microvessel density compared with that in the control (P < .05).
      Treatment with anti-VEGF antibody (bevacizumab) inhibited tumor growth,
      dissemination, and ascites production in mice injected with cells expressing WT1 
      17AA/- KTS. The overexpression of WT1 - 17AA/- KTS induced a more aggressive
      phenotype in ovarian cancer cells through VEGF up-regulation in an in vivo
      ovarian cancer model. Our findings indicated that WT1 - 17AA/- KTS enhanced
      tumorigenic activity and could decreased patient survival through up-regulation
      of VEGF expression in ovarian cancers. 

PMID- 25389454
TI  - Comparative Study of 17-AAG and NVP-AUY922 in Pancreatic and Colorectal Cancer
      Cells: Are There Common Determinants of Sensitivity?
AB  - The use of heat shock protein 90 (Hsp90) inhibitors is an attractive
      antineoplastic therapy. We wanted to compare the effects of the benzoquinone 17
      allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) and the novel
      isoxazole resorcinol-based Hsp90 inhibitor NVP-AUY922 in a panel of pancreatic
      and colorectal carcinoma cell lines and in colorectal primary cultures derived
      from tumors excised to patients. PANC-1, CFPAC-1, and Caco-2 cells were
      intrinsically resistant to 17-AAG but sensitive to NVP-AUY922. Other cellular
      models were sensitive to both inhibitors. Human epidermal growth factor receptor
      receptors and their downstream signaling pathways were downregulated in
      susceptible cellular models, and concurrently, Hsp70 was induced. Intrinsic
      resistance to 17-AAG did not correlate with expression of ATP-binding cassette
      transporters involved in multidrug resistance. Some 17-AAG-resistant, NVP-AUY922
      sensitive cell lines lacked NAD(P)H: quinone oxidoreductase 1 (NQO1) enzyme and
      activity. However, colorectal LoVo cells still responded to both drugs in spite
      of having undetectable levels and activity of NQO1. Pharmacological and biologic
      inhibition of NQO1 did not confer resistance to 17-AAG in sensitive cell lines.
      Therefore, even though 17-AAG sensitivity is related to NQO1 protein levels and
      enzymatic activity, the absence of NQO1 does not necessarily convey resistance to
      17-AAG in these cellular models. Moreover, NVP-AUY922 does not require NQO1 for
      its action and is a more potent inhibitor than 17-AAG in these cells. More
      importantly, we show in this report that NVP-AUY922 potentiates the inhibitory
      effects of chemotherapeutic agents, such as gemcitabine or oxaliplatin, and other
      drugs that are currently being evaluated in clinical trials as antitumor agents.

PMID- 25389455
TI  - Increased MET Gene Copy Number but Not mRNA Level Predicts Postoperative
      Recurrence in Patients with Non-Small Cell Lung Cancer.
AB  - The aim of the present study was to investigate the relationship of MET copy
      number (CN) and MET mRNA expression to other molecular alterations,
      clinicopathologic characteristics, and survival of patients with resected non
      small cell lung cancer. One hundred fifty-one paired surgical samples of tumor
      and tumor-distant normal lung tissues were analyzed by comparative quantitative
      polymerase chain reaction (PCR) methods with commercially available assays and
      the CopyCaller software v. 1.0 for post-PCR data processing (downloadable from
      www.appliedbiosystems.com). MET copy gain (set as more than 3.0 copies per cell)
      was found in 18.5% of the samples and occurred more frequently in the
      adenocarcinomas (ADCs) with an increased epidermal growth factor receptor (EGFR)
      or human epidermal growth factor receptor 2 (HER2) CN (P = .001 and .030 for EGFR
      and HER2, respectively) and in the ADCs with EGFR activating mutations (P = .051)
      but did not correlate with KRAS dosage or mutational status. MET mRNA level was
      1.76-fold higher [95% confidence interval (CI), 1.29-2.40] in the tumor compared
      to unaffected lung tissue and associated significantly with MET CN (beta
      coefficient, 1.51; 95% CI, 1.22-1.87; P < .001). In the multivariable analysis,
      patients diagnosed with ADC with increased MET CN had a significantly higher risk
      of disease recurrence (hazard ratio, 1.76; 95% CI, 1.20-2.57; P = .004). An
      increased MET CN in combination with histologic type appears to be a prognostic
      factor in patients with ADC after a curative surgery. 

PMID- 25389456
TI  - Fractioned dose regimen of sunitinib for patients with gastrointestinal stromal
      tumor: a pharmacokinetic and treatment efficacy study.
AB  - AIM: Sunitinib has shown benefit in patients with imatinib (IM)-resistant
      gastrointestinal stromal tumor (GIST). However, its advantages are somewhat
      diminished because of associated toxicities. Herein, we clarify the efficacy and
      safety of fractioned dose regimen of sunitinib by a pharmacokinetic and efficacy
      study. MATERIALS AND METHODS: Between 2001 and March 2013, a total of 214
      patients with metastatic GIST was treated at Chang Gung Memorial Hospital. Among
      them, 55 (11.6%) patients who received sunitinib were investigated. One group of
      patients was administered with standard dose of once-daily sunitinib (standard
      dose group) and the other group was administered with standard total daily dose
      of sunitinib in fractioned doses (fractioned dose group). RESULTS: Thirty-two
      male and 23 female patients with a median age of 55 years received sunitinib. The
      median duration of sunitinib administration was 9.2 months. The clinical benefit
      was 65.2%. The mean peak blood level of sunitinib in patients with fractioned
      doses was significantly lower than that in those with once-daily dose (83.4 vs
      50.1 ng/ml, P = .01). The rates of adverse effects of hand-foot syndrome,
      mucositis, and yellow skin were significantly decreased by fractioned doses of
      sunitinib. However, the progression-free and overall survival did not differ
      between patients with different treatment regimens. CONCLUSION: The fractioned
      dose regimen of sunitinib appears to be a safe and effective treatment for
      patients with IM-resistant/intolerant GISTs. Significantly decreased toxicity of
      this regimen could be explained by significantly lower peak sunitinib blood
      level. However, the treatment efficacy is not reduced by this regimen.

PMID- 25389457
TI  - Rewriting the epigenetic code for tumor resensitization: a review.
AB  - In cancer chemotherapy, one axiom, which has practically solidified into dogma,
      is that acquired resistance to antitumor agents or regimens, nearly inevitable in
      all patients with metastatic disease, remains unalterable and irreversible,
      rendering therapeutic rechallenge futile. However, the introduction of epigenetic
      therapies, including histone deacetylase inhibitors (HDACis) and DNA
      methyltransferase inhibitors (DNMTIs), provides oncologists, like computer
      programmers, with new techniques to "overwrite" the modifiable software pattern
      of gene expression in tumors and challenge the "one and done" treatment
      prescription. Taking the epigenetic code-as-software analogy a step further, if
      chemoresistance is the product of multiple nongenetic alterations, which develop
      and accumulate over time in response to treatment, then the possibility to hack
      or tweak the operating system and fall back on a "system restore" or "undo"
      feature, like the arrow icon in the Windows XP toolbar, reconfiguring the tumor
      to its baseline nonresistant state, holds tremendous promise for turning
      advanced, metastatic cancer from a fatal disease into a chronic, livable
      condition. This review aims 1) to explore the potential mechanisms by which a
      group of small molecule agents including HDACis (entinostat and vorinostat),
      DNMTIs (decitabine and 5-azacytidine), and redox modulators (RRx-001) may
      reprogram the tumor microenvironment from a refractory to a nonrefractory state,
      2) highlight some recent findings, and 3) discuss whether the current "once
      burned forever spurned" paradigm in the treatment of metastatic disease should be
      revised to promote active resensitization attempts with formerly failed
      chemotherapies. 

PMID- 25389458
TI  - The combination of platelet count and neutrophil lymphocyte ratio is a predictive
      factor in patients with esophageal squamous cell carcinoma.
AB  - OBJECTIVE: The prognostic value of inflammation indexes in esophageal cancer was
      not established. In this study, therefore, both prognostic values of Glasgow
      prognostic score (GPS) and combination of platelet count and neutrophil
      lymphocyte ratio (COP-NLR) in patients with esophageal squamous cell carcinoma
      (ESCC) were investigated and compared. METHODS: This retrospective study included
      375 patients who underwent esophagectomy for ESCC. The cancer-specific survival
      (CSS) was calculated by the Kaplan-Meier method, and the difference was assessed
      by the log-rank test. The GPS was calculated as follows: patients with elevated C
      reactive protein (> 10 mg/l) and hypoalbuminemia (< 35 g/l) were assigned to
      GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0,
      respectively. The COP-NLR was calculated as follows: patients with elevated
      platelet count (> 300 * 10(9)/l) and neutrophil lymphocyte ratio (> 3) were
      assigned to COP-NLR2. Patients with one or no abnormal value were assigned to COP
      NLR1 or COP-NLR0, respectively. RESULTS: The 5-year CSS in patients with GPS0, 1,
      and 2 was 50.0%, 27.0%, and 12.5%, respectively (P < .001). The 5-year CSS in
      patients with COP-NLR0, 1, and 2 was 51.8%, 27.0%, and 11.6%, respectively (P <
      .001). Multivariate analysis showed that both GPS (P = .003) and COP-NLR (P =
      .003) were significant predictors in such patients. In addition, our study
      demonstrated a similar hazard ratio (HR) between COP-NLR and GPS (HR = 1.394 vs
      HR = 1.367). CONCLUSIONS: COP-NLR is an independent predictive factor in patients
      with ESCC. We conclude that COP-NLR predicts survival in ESCC similar to GPS.

PMID- 25389459
TI  - Relationship Between LAPTM4B Gene Polymorphism and Susceptibility of Malignant
      Melanoma in Chinese Patients.
AB  - Lysosomal-associated protein transmembrane 4 beta (LAPTM4B) is known as an
      oncogene associated with many human malignant tumors. There are two alleles of
      the gene, LAPTM4B*1 and LAPTM4B*2. Previous studies have shown that LAPTM4B
      polymorphism contributes to the risk of many cancers. This case-control study was
      to investigate the relationship between LAPTM4B gene polymorphism and
      susceptibility of malignant melanoma. The genotypes of LAPTM4B were determined in
      617 control subjects and 220 patients with malignant melanoma by utilizing
      polymerase chain reaction based on specific primers. The genotypic distribution
      of LAPTM4B and Hardy-Weinberg equilibrium were analyzed by chi (2) test. Odds
      ratio and 95% confidence interval was calculated by unconditional logistic
      regression. The distributions of LAPTM4B genotypes were significantly different
      between melanoma patients (45.9% for *1/1, 46.4% for *1/2 and 7.7 for *2/2) and
      controls (54.5% for *1/1, 39.9% for *1/2 and 5.7 for *2/2). LAPTM4B *1/2 and
      LAPTM4B *2/2 had a 1.396-fold and 1.619-fold higher risk for melanoma occurrence
      than *1/1, and subjects with LAPTM4B*2 have a 1.308-fold higher risk than
      LAPTM4B*1 carriers. No association between LAPTM4B genotypes and gender, age,
      subtype, Clark level of invasion, Breslow thickness, ulceration, clinical stage,
      and C-KIT, BRAF gene mutation status was observed. LAPTM4B*2 is associated with
      the high risk of malignant melanoma and carrying LAPTM4B *2 may be a susceptible
      factor to Chinese melanoma patients. 

PMID- 25389462
TI  - Compensation claims for chiropractic in Denmark and Norway 2004-2012.
AB  - BACKGROUND: Adverse events are commonly observed in all parts of health care and
      have been reported extensively following manual therapy, including chiropractic.
      The majority of reported adverse events following chiropractic care are mild,
      transitory and self-limiting. However, little is known about patient filed
      compensation claims related to the chiropractic consultation process. The aim of
      this study was to describe claims reported to the Danish Patient Compensation
      Association and the Norwegian System of Compensation to Patients related to
      chiropractic from 2004 to 2012. METHODS: All finalized compensation claims
      involving chiropractors reported to one of the two associations between 2004 and
      2012 were assessed for age, gender, type of complaint, decisions and appeals.
      Descriptive statistics were used to describe the study population. RESULTS: 338
      claims were registered in Denmark and Norway between 2004 and 2012 of which 300
      were included in the analysis. 41 (13.7%) were approved for financial
      compensation. The most frequent complaints were worsening of symptoms following
      treatment (n = 91, 30.3%), alleged disk herniations (n = 57, 19%) and cases with
      delayed referral (n = 46, 15.3%). A total financial payment of ?2,305,757 (median
      payment ?7,730) were distributed among the forty-one cases with complaints
      relating to a few cases of cervical artery dissection (n = 11, 5.7%) accounting
      for 88.7% of the total amount. CONCLUSION: Chiropractors in Denmark and Norway
      received approximately one compensation claim per 100.000 consultations. The
      approval rate was low across the majority of complaint categories and lower than
      the approval rates for general practioners and physiotherapists. Many claims can
      probably be prevented if chiropractors would prioritize informing patients about
      the normal course of their complaint and normal benign reactions to treatment.

PMID- 25389460
TI  - A pilot study of diffusion-weighted MRI in patients undergoing neoadjuvant
      chemoradiation for pancreatic cancer.
AB  - PURPOSE: In the current study we examined the ability of diffusion MRI (dMRI) to
      predict pathologic response in pancreatic cancer patients receiving neoadjuvant
      chemoradiation. METHODS: We performed a prospective pilot study of dMRI in
      patients with resectable pancreatic cancer. Patients underwent dMRI prior to
      neoadjuvant chemoradiation. Surgical specimens were graded according to the
      percent tumor cell destruction. Apparent diffusion coefficient (ADC) maps were
      used to generate whole-tumor derived ADC histogram distributions and mean ADC
      values. The primary objective of the study was to correlate ADC parameters with
      pathologic and CT response. RESULTS: Ten of the 12 patients enrolled on the study
      completed chemoradiation and had surgery. Three were found to be unresectable at
      the time of surgery and no specimen was obtained. Out of the 7 patients who
      underwent pancreaticoduodenectomy, 3 had a grade III histopathologic response (>
      90% tumor cell destruction), 2 had a grade IIB response (51% to 90% tumor cell
      destruction), 1 had a grade IIA response (11% to 50% tumor cell destruction), and
      1 had a grade I response (> 90% viable tumor). Median survival for patients with
      a grade III response, grade I-II response, and unresectable disease were 25.6,
      18.7, and 6.1 months, respectively. There was a significant correlation between
      pre-treatment mean tumor ADC values and the amount of tumor cell destruction
      after chemoradiation with a Pearson correlation coefficient of 0.94 (P = .001).
      Mean pre-treatment ADC was 161 * 10(- 5) mm(2)/s (n = 3) in responding patients
      (> 90% tumor cell destruction) compared to 125 * 10(- 5) mm(2)/s (n = 4) in non
      responding patients (> 10% viable tumor). CT imaging showed no significant change
      in tumor size in responders or non-responders. CONCLUSIONS: dMRI may be useful to
      predict response to chemoradiation in pancreatic cancer. In our study, tumors
      with a low ADC mean value at baseline responded poorly to standard chemoradiation
      and would be candidates for intensified therapy.

PMID- 25383181
TI  - Developing sustainable software solutions for bioinformatics by the " Butterfly"
      paradigm.
AB  - Software design and sustainable software engineering are essential for the long
      term development of bioinformatics software. Typical challenges in an academic
      environment are short-term contracts, island solutions, pragmatic approaches and
      loose documentation. Upcoming new challenges are big data, complex data sets,
      software compatibility and rapid changes in data representation. Our approach to
      cope with these challenges consists of iterative intertwined cycles of
      development (" Butterfly" paradigm) for key steps in scientific software
      engineering. User feedback is valued as well as software planning in a
      sustainable and interoperable way. Tool usage should be easy and intuitive. A
      middleware supports a user-friendly Graphical User Interface (GUI) as well as a
      database/tool development independently. We validated the approach of our own
      software development and compared the different design paradigms in various
      software solutions. 

PMID- 25383183
TI  - The 'SAR Matrix' method and its extensions for applications in medicinal
      chemistry and chemogenomics.
AB  - We describe the 'Structure-Activity Relationship (SAR) Matrix' (SARM) methodology
      that is based upon a special two-step application of the matched molecular pair
      (MMP) formalism. The SARM method has originally been designed for the extraction,
      organization, and visualization of compound series and associated SAR information
      from compound data sets. It has been further developed and adapted for other
      applications including compound design, activity prediction, library extension,
      and the navigation of multi-target activity spaces. The SARM approach and its
      extensions are presented here in context to introduce different types of
      applications and provide an example for the evolution of a computational
      methodology in pharmaceutical research. 

PMID- 25383185
TI  - CyKEGGParser: tailoring KEGG pathways to fit into systems biology analysis
      workflows.
AB  - The KEGG pathway database is a widely accepted source for biomolecular pathway
      maps. In this paper we present the CyKEGGParser app (
      http://apps.cytoscape.org/apps/cykeggparser) for Cytoscape 3 that allows
      manipulation with KEGG pathway maps. Along with basic functionalities for pathway
      retrieval, visualization and export in KGML and BioPAX formats, the app provides
      unique features for computer-assisted adjustment of inconsistencies in KEGG
      pathway KGML files and generation of tissue- and protein-protein interaction
      specific pathways. We demonstrate that using biological context-specific KEGG
      pathways created with CyKEGGParser makes systems biology analysis more sensitive
      and appropriate compared to original pathways. 

PMID- 25383184
TI  - Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats
      with focal ischemia.
AB  - The pursuit of targeting multiple pathways in the ischemic cascade of cerebral
      stroke is a promising treatment option. We examined the regenerative potential of
      conditioned medium derived from rat and human apoptotic mononuclear cells (MNC),
      rMNC (apo sec) and hMNC (apo sec), in experimental stroke. We performed middle
      cerebral artery occlusion on Wistar rats and administered apoptotic MNC
      secretomes intraperitoneally in two experimental settings. Ischemic lesion
      volumes were determined 48 hours after cerebral ischemia. Neurological
      evaluations were performed after 6, 24 and 48 hours. Immunoblots were conducted
      to analyze neuroprotective signal-transduction in human primary glia cells and
      neurons. Neuronal sprouting assays were performed and neurotrophic factors in
      both hMNC (apo sec) and rat plasma were quantified using ELISA. Administration of
      rat as well as human apoptotic MNC-secretomes significantly reduced ischemic
      lesion volumes by 36% and 37%, respectively. Neurological examinations revealed
      improvement after stroke in both treatment groups. Co-incubation of human
      astrocytes, Schwann cells and neurons with hMNC (apo sec) resulted in activation
      of several signaling cascades associated with the regulation of cytoprotective
      gene products and enhanced neuronal sprouting in vitro. Analysis of neurotrophic
      factors in hMNC (apo sec) and rat plasma revealed high levels of brain derived
      neurotrophic factor (BDNF). Our data indicate that apoptotic MNC-secretomes
      elicit neuroprotective effects on rats that have undergone ischemic stroke. 

PMID- 25389467
TI  - Application of veno-arterial-venous extracorporeal membrane oxygenation in
      differential hypoxia.
AB  - Veno-arterial extracorporeal membrane oxygenation (ECMO) through the femoral vein
      and artery may cause differential hypoxia, i.e., lower PaO2 in the upper body
      than in the lower body, because of normal cardiac output with severe impairment
      of pulmonary function. Hereby, we report the diagnosis and the treatment of
      differential hypoxia caused by veno-arterial ECMO. A 39-year-old man received
      cardiopulmonary resuscitation from a cardiac arrest due to acute myocardial
      infarction. Even after more than 30 min of resuscitation, spontaneous circulation
      had not resumed. Next, we performed veno-arterial ECMO through the femoral artery
      and vein, and the patient recovered consciousness on the second day of ECMO. On
      day 5 of ECMO, he lost consciousness again and presented a generalized tonic
      clonic seizure, and an electroencephalogram showed delta waves suggesting diffuse
      cerebral cortical dysfunction. While an echocardiogram revealed improvements in
      myocardial function, a follow up chest radiograph showed increasing massive
      parenchymal infiltrations, and gas analysis of blood from the right radial artery
      revealed severe hypoxemia. These findings indicated a definite diagnosis of
      differential hypoxia, and therefore, we inserted a 17-Fr cannula into the left
      subclavian vein as a return cannula. The patient's consciousness and pulmonary
      infiltrations were improved 2 days after veno-arterial-venous ECMO, and the
      electroencephalogram showed normal findings. To our knowledge, this is the first
      report of successful clinical management of differential hypoxia. We suggest that
      veno-arterial-venous ECMO could be the treatment of choice for differential
      hypoxia resulting from veno-arterial ECMO. 

PMID- 25389468
TI  - Risk factors for fatal and nonfatal road crashes in iran.
AB  - BACKGROUND: Road traffic injuries are among the leading causes of death in the
      world and Iran. OBJECTIVES: The aim of this study was to assess the role of age,
      sex, education, and time of accident on human casualties and mortalities of road
      crashes in Iran. MATERIALS AND METHODS: This study was based on data gathered by
      Iranian Police Department from the records of road crashes from April 4, 2008
      through April 4, 2009. Road crashes are categorized into three types: with no
      human casualties, with injuries, and with human mortalities. RESULTS: The largest
      rate of human causalities was observed in people aged between 25 to 34 years (P <
      0.001). Illiterate people had 81% smaller odds of causality in road crashes (P <
      0.001) in comparison with those with a kind of academic education. Overall, 73.4%
      of crashes had happened during the last ten days of a month were with human
      casualties (P < 0.001) and human casualties rate was slightly higher in crashes
      happened between 1 AM to 5 AM Fatality rate was slightly higher in the females
      (OR = 2.6, P = 0.068). The smallest odds of fatality were found in the people
      aged between 18 to 24 years and the highest odds were seen in people >= 55 years
      of age (P < 0.001). In people with a university education, 61.9% of crashes were
      with fatality (P = 0.026). In addition, 82.8% of crashes during winter, 60.2% of
      crashes during autumn, and 35.8% of crashes during summer were with mortalities.
      Overall, 78.3% of crashes with human casualties that had happened during 1 AM to
      5 AM led to mortalities. There was also a significant association between injury
      and its intensity with fastening seatbelts. CONCLUSIONS: Older age, university
      degrees, female sex, wintertime, and the time of accident seem to be the most
      important risk factors in road crashes that lead to fatalities in Iran. Drivers
      in Iran should be informed and trained regarding these risk factors, which have
      direct effect on casualties and mortalities in road crashes.

PMID- 25389469
TI  - Occupational stress and cardiovascular risk factors in high-ranking government
      officials and office workers.
AB  - BACKGROUND: Cardiovascular diseases are among the most important sources of
      mortality and morbidity, and have a high disease burden. There are some major
      well-known risk factors, which contribute to the development of these diseases.
      Occupational stress is caused due to imbalance between job demands and
      individual's ability, and it has been implicated as an etiology for
      cardiovascular diseases. OBJECTIVES: This study was conducted to evaluate the
      cardiovascular risk factors and different dimensions of occupational stress in
      high-ranking government officials, comparing an age and sex-matched group of
      office workers with them. PATIENTS AND METHODS: We invited 90 high-ranking
      officials who managed the main governmental offices in a city, and 90 age and sex
      matched office workers. The subjects were required to fill the occupational role
      questionnaire (Osipow) which evaluated their personal and medical history as well
      as occupational stress. Then, we performed physical examination and laboratory
      tests to check for cardiovascular risk factors. Finally, the frequency of
      cardiovascular risk factors and occupational stress of two groups were compared.
      RESULTS: High-ranking officials in our study had less work experience in their
      current jobs and smoked fewer pack-years of cigarette, but they had higher waist
      and hip circumference, higher triglyceride level, more stress from role overload
      and responsibility, and higher total stress score. Our group of office workers
      had more occupational stress because of role ambiguity and insufficiency, but
      their overall job stress was less than officials. CONCLUSIONS: The officials have
      higher scores in some dimensions of occupational stress and higher overall stress
      score. Some cardiovascular risk factors were also more frequent in managers.

PMID- 25389470
TI  - Disclosure of HIV Status and Social Support Among People Living With HIV.
AB  - BACKGROUND: Disclosure of HIV is important for improving self-care behaviors,
      psychological well-being, commitment to the treatment, and reducing risk of
      transmission. One of the major benefits of disclosure is social support, which is
      an essential resource for effective coping with HIV infection. However, receiving
      any social support requires disclosing of HIV status. OBJECTIVES: This study
      aimed to determine the disclosure of HIV status and its related factors such as
      social support in addition to demographic and disease characteristics among
      people living with HIV in Iran. PATIENTS AND METHODS: This cross-sectional study,
      using simple random sampling, was carried out on 175 people with HIV/AIDS who
      referred to Behavioral Counseling Centers. The self-administrated, Norbeck Social
      Support Questionnaire was used to measure social support. Disclosure of HIV
      status was assessed with an investigator-designed questions. Multiple logistic
      regression analysis with backward Likelihood Ratio method was applied to identify
      the adjusted odds ratio between disclosure as dependent variable and demographic
      variables, social support as independent variables. RESULTS: Participants were
      often disclosed their HIV status to family members. But there were differences
      about disclosure of HIV status within the context of the family. Family members
      were perceived as more supportive. Multiple logistic regression analysis
      demonstrates that the gender (adjusted OR = 0.181; 95% CI .068-0.479), CD4 cell
      count (adjusted OR = 0.997; 95% CI 0.994-0.999), route of transmission (injection
      drug user [adjusted OR = 9.366; 95% CI 3.358-26.123] and other routes [tattooing,
      mother to child, dental services, etc.], [adjusted OR = 3.752; 95% CI 1.157
      12.167]), and functional support variable (adjusted OR = 1.007; 95% CI 1.001
      1.013) remained in the model as significant predictors for disclosure.
      CONCLUSIONS: The results of this study regarding disclosure of HIV status and its
      relations to social support and some demographic variables can provide an
      understanding based on the evidence for promotion of knowledge and coping
      interventions about people living with HIV/AIDS and their perceived social
      support status.

PMID- 25389471
TI  - Serum lectin-like oxidized-low density lipoprotein receptor-1 and adiponectin
      levels are associated with coronary artery disease accompanied with metabolic
      syndrome.
AB  - BACKGROUND: Coronary artery disease (CAD) is a major public health problem for
      developed and developing countries and is the single leading cause of death
      worldwide. OBJECTIVES: There is very few evidence regarding changes of both serum
      Lectin-like oxidized-low density lipoprotein receptor-1 (LOX-1) and adiponectin
      in patients with CAD accompanied with metabolic syndrome (MS). Here we aimed to
      evaluate serum levels of LOX-1 and adiponectin in patients with CAD accompanied
      with MS. PATIENTS AND METHODS: Thirty patients with coronary artery disease
      without metabolic syndrome, 30 patients with coronary artery disease and
      metabolic syndrome, 30 ones with metabolic syndrome and 30 healthy subjects were
      enrolled. For all subjects, a questionnaire was filled to collect data, and
      peripheral blood samples were collected aseptically from the antecubital vein to
      measure serum Lectin-like oxidized-low density lipoprotein receptor-1 and
      adiponectin levels by enzyme-linked immunosorbent assay. RESULTS: Serum LOX-1
      level was highest in CAD + MS group; the difference between control and disease
      groups was statistically significant (P < 0.001). Adiponectin level had the
      lowest value in CAD + MS group; the difference between control and disease groups
      was statistically significant (P < 0.05). No significant differences were
      observed in serum Lectin-like oxidized-low density lipoprotein receptor-1and
      adiponectin in patients with different ages and gender. Serum LOX-1 level was
      changed negatively and linearly (R2 = 0.721) correlated with adiponectin level in
      different groups. CONCLUSIONS: Patient with CAD and MS had higher risk than those
      with only CAD because of lipid and glucose metabolism abnormalities. Combination
      measurements of serum LOX-1 and adiponectin levels may be helpful to evaluate the
      severity of CAD together with MS.

PMID- 25389472
TI  - Prophylactic aminophylline for prevention of apnea at higher-risk preterm
      neonates.
AB  - BACKGROUND: A few studies have been carried on preventive drugs for apnea of
      preterm neonates. OBJECTIVES: This study aimed to assess the safety and
      prophylactic effects of aminophylline on the incidence of apnea in premature
      neonates. PATIENTS AND METHODS: This study was a randomized clinical trial (RCT)
      research. The prophylactic effect of aminophylline on apnea was investigated in
      premature babies in our NICU (IRAN-Isfahan). In the study group (A), 5 mg/kg
      aminophylline was initially administered as a loading dose. Then, every 8 hours,
      1.5 mg/kg was given as maintenance dose for the next 10 days. In the control
      group (C), no aminophylline was used during the first ten days of life. RESULTS:
      Fifty-two neonates were randomized for the study and all of them completed it.
      Primary outcomes were clearly different between the two groups. Only 2 infants
      (7.7%) who had been placed in aminophylline group developed apnea, as compared to
      16 infants (61.5%) in the control group (P < 0.001). Three and four neonates
      (11.5%, 15.4%) in the aminophylline group developed bradycardia and cyanosis
      respectively, as compared to 16 infants (61.5%) who did not receive aminophylline
      (P < 0.001). Median time of need to NCPAP (Nasal Continuous Positive Airway
      Pressure) was 1 (0 - 4) days and 2.5 (0.5 - 6.5) days in group A and C,
      respectively (P = 0.03). No side effects were reported in neonates (P > 0.999).
      Median time of hospitalization was shorter in aminophylline group (P = 0.04).
      CONCLUSIONS: This study supports the preventative effects of aminophylline on
      apnea in extreme premature infants. In other words, the more premature an infant,
      the greater the preventative effect of aminophylline on the incidence of apnea
      and bradycardia.

PMID- 25389473
TI  - Comparison of ondansetron and meperidine for treatment of postoperative
      shivering: a randomized controlled clinical trial.
AB  - BACKGROUND: The involved neurotransmitter pathways in the postoperative shivering
      (POS) are poorly understood. Recently, 5-hydroxytryptamine 3 (5-HT3) receptor
      antagonists have been reported to prevent POS. We investigated the effect of
      ondansetron, a 5-HT3 antagonist that is used to treat postoperative nausea and
      vomiting, on shivering. OBJECTIVES: This study aimed to compare the efficacy of
      ondansetron and meperidine in the treatment of shivering after general
      anesthesia. PATIENTS AND METHODS: In this double-blinded randomized clinical
      trial, 83 patients (age range, 18-60 years) who had shivering after general
      anesthesia were randomly allocated to any of these three groups: Group A, (number
      = 27) received 4 mg of intravenous ondansetron, Group B, (number = 27) received 8
      mg of intravenous ondansetron, and Group C, (number = 29) received 0.4 mg/kg of
      intravenous meperidine at recovery room. The surface temperatures and the
      incidence as well as intensity of shivering were recorded. RESULTS: Shivering was
      controlled in 16 patients (59%) in Group A, 22 (81%) in Group B, and 25 (86%) in
      Group C (P = 0.01). Within each group, there were no significant differences
      among the surface temperature in recovery room. Patients in groups A and B had
      significantly lower incidence of nausea and vomiting than group C (P = 0.01).
      CONCLUSIONS: Ondansetron and meperidine have similar effects on shivering. We
      concluded that 8 mg of intravenous ondansetron can control shivering and this is
      the dose of choice, especially in patients with POS with nausea and vomiting.

PMID- 25389474
TI  - The assessment of undergraduate medical students' satisfaction levels with the
      objective structured clinical examination.
AB  - BACKGROUND: The objective structured clinical examination (OSCE) has been
      introduced as an efficient method for the assessment of medical students.
      OBJECTIVES: The aim of the present study was to determine the satisfaction level
      of undergraduate medical students of internal medicine department with the OSCE.
      MATERIALS AND METHODS: This was a descriptive cross-sectional study, performed on
      all available undergraduate students at the end of their internal medicine
      training period in Mashhad University of Medical Sciences. The students responded
      to 15 multiple-choice questions with confirmed validity and reliability. RESULTS:
      The majority of the students (94.5%) had a positive attitude toward the OSCE and
      mentioned that the OSCE format was a more appropriate type of exam than other
      methods of testing; however, 79.1% thought that the OSCE format was stressful. In
      addition, the participants' sex had no effect on their level of satisfaction with
      the examination. Likewise, there was no significant correlation between their
      level of satisfaction and their age, marital status, or lack of previous
      experience with this type of exam. CONCLUSIONS: If the exam standards are met and
      a uniform dispersion of the scientific content is maintained, the OSCE method of
      assessment can be recommended as an efficient and applicable method for assessing
      medical students.

PMID- 25389475
TI  - Association of MEF2A gene polymorphisms with coronary artery disease.
AB  - BACKGROUND: Coronary Artery Disease (CAD) is the most common cause of death
      worldwide. MEF2A directly regulates target genes in the process of muscle
      development. This gene product is a transcription factor. MEF2A protein in
      homodimer or heterodimer forms binds to A/T-rich cis elements with conserved
      sequence in promoter, regulator, and enhancer of many genes, which are
      determining in evolution and development of skeletal, heart, and smooth muscle
      cells, especially endothelial cells. In fact, this protein maximizes the activity
      of these elements. OBJECTIVES: The two MEF2A gene polymorphisms that were
      proposed to have an association with CAD are rs34851361 (A/G) and rs325400 (T/G)
      SNPs. This study aimed to examine these associations. PATIENTS AND METHODS: This
      study was a molecular case-control study. Blood samples were collected from 300
      patients with CAD and 150 healthy people from Golestan and Imam Khomeini
      Hospitals, Ahvaz, Iran. In both groups, angiography had confirmed the presence or
      lack of stenosis. Association of rs34851361 and rs325400 with CAD was evaluated
      by PCR and then restriction fragment length polymorphism (RFLP) analysis was
      performed. RESULTS: Chi square test showed no association between rs34851361 SNP
      and CAD (chi(2) = 3.59, df = 2, and P = 0.16); however, there was an association
      between rs325400 SNP and CAD (chi(2) = 24.77, df = 2, and P < 0.001). A/T
      haplotype showed association with CAD and G/G and G/T showed protective effect
      against CAD. CONCLUSIONS: The results of this study show that rs325400
      polymorphism is in association with CAD; meanwhile, none of the rs34851361
      genotypes was associated with CAD.

PMID- 25389476
TI  - Low frequency repetitive transcranial magnetic stimulation to improve motor
      function and grip force of upper limbs of patients with hemiplegia.
AB  - BACKGROUND: Stroke is the most common and debilitating neurological disorder
      among adults, and is a sudden onset of neurological signs caused by brain blood
      vessels impairments. OBJECTIVES: Some new therapeutic methods focus on the use of
      magnetic stimulation to produce therapeutic effects by inducing the currents. The
      aim of this study is to determine the effects of rTMS plus routine rehabilitation
      on hand grip and wrist motor functions in patients with hemiplegia, and compare
      with pure routine rehabilitation programs. PATIENTS AND METHODS: In this study,
      12 patients with hemiplegia were randomly divided in two groups. Control group,
      received the rehabilitation program with placebo magnetic stimulation, and the
      experimental group, received magnetic stimulation with routine rehabilitation
      program for 10 sessions for three times per week. Pre and post evaluations of
      treatment performed using Barthel and Fugl-Meyer indices and dynamometers.
      RESULTS: In the control group, Barthel and Fugl-Meyer indices showed significant
      improvement (P = 0.01, P = 0.00), while in the experimental group, significant
      improvement in Barthel and Fugl-Meyer indices and dynamometers has been observed
      (P = 0.01, P = 0.00, P = 0.007). CONCLUSIONS: rTMS can improve hand muscle force
      and functions of patients with chronic hemiplegia, while conventional treatment
      is not effective.

PMID- 25389477
TI  - Comparison of topical nifedipine with oral nifedipine for treatment of anal
      fissure: a randomized controlled trial.
AB  - BACKGROUND: Medical sphincterotomy has gained popularity as a treatment for anal
      fissure. Calcium channel blockers in topical forms could also be appropriate with
      low adverse effects. OBJECTIVES: This was a prospective randomized controlled
      trial to compare topical and oral nifedipine in the treatment of chronic anal
      fissure. PATIENTS AND METHODS: A prospective randomized controlled trial was
      conducted at two centers of Shahed University. One hundred and thirty patients
      with chronic anal fissure aged 18 to 60 years managed in our clinics were
      included in this study. The patients were randomly divided into two groups. Sixty
      five patients received topical nifedipine (TN) and the same number received oral
      nifedipine (ON). RESULTS: Ulcer healing occurred in 43 (73.33%) of topical
      nifedipine group compared to 29 (49.5%) patients in oral nifedipine, which was
      significantly different (P < 0.05). Side effects such as headache and flushing in
      oral nifedipine group were more prevalent than topical nifedipine, which was
      statistically different. Recurrence rates were the same after six months of
      follow-up. CONCLUSIONS: Although oral nifedipine can reduce symptom and signs of
      anal fissure, topical nifedipine has a superior role for anal fissure treatment
      with higher healing rate and lower side effects.

PMID- 25389478
TI  - A comparison of second and third generations combined oral contraceptive pills'
      effect on mood.
AB  - BACKGROUND: Most women taking combined oral contraceptives (COCs) are satisfied
      with their contraceptive method. However, one of the most common reasons reported
      for discontinuation of combined oral contraceptives (COCs) is mood deterioration.
      OBJECTIVES: This study aimed to compare effects of the second and third
      generation oral contraceptive pills on the mood of reproductive women. MATERIALS
      AND METHODS: This randomized, double-blind, controlled clinical trial was
      conducted in reproductive women at health centers in Tehran, Iran. Participants
      were randomized into the second and third generation oral contraceptive groups.
      Positive and negative moods were recorded using positive affect, negative affect
      scale (PANAS) tools at the end the second and fourth months of the study. Data
      analysis was carried out using ANOVA and P Values < 0.05 was considered
      significant. RESULTS: Statistically significant difference was seen in positive
      and negative mood changes in women receiving contraceptive pills. The second
      generation oral contraceptive pills resulted in a decrease in positive mood (95%
      CI: 43.39 to 38.32 in second month and 43.39 to 26.05 in four month) and increase
      in negative mood (95% CI: 14.23 to 22.04 in second month and 14.23 to 32.26 in
      four month - P < 0.001), but the third generation led to an increase in positive
      mood (95% CI: 22.42 to 25.60 in second month and 22.42 to 33.87 in four month)
      and decrease in negative mood (95% CI: 36.78 to 31.97 in second month and 36.78
      to 22.65 in four month - P < 0.001). CONCLUSIONS: Third generation combined oral
      contraceptive pills have a better effect on mood in women in reproductive ages
      than the second generation pills. It can be recommended as a proper combined oral
      contraceptive in Iran.

PMID- 25389479
TI  - Thin Cord Syndrome in a Thirty-year-old Pregnant Woman.
AB  - INTRODUCTION: The umbilical cord anomalies directly effect on the life quality of
      the fetus. It can lead to fetal death or many problems during pregnancy and
      delivery. Early detection of these abnormalities is of particular importance.
      CASE PRESENTATION: We report a case of thin cord syndrome (TCS) in a 30-year-old
      pregnant woman with suprapubic pain. After termination of pregnancy,
      histopathologic assessment confirmed the TCS. CONCLUSIONS: In all cases with
      suspected abortion, the umbilical cord disorder should be considered.

PMID- 25389480
TI  - Importance of neutrophil gelatinase-associated lipocalin in differential
      diagnosis of acute and chronic renal failure.
AB  - BACKGROUND: Neutrophil Gelatinase-associated Lipocalin (NGAL) protein is easily
      detected in the blood and urine soon after acute renal injury. NGAL gains
      features of an early, sensitive and noninvasive biomarker for acute renal injury.
      Recent evidences suggest that its expression is also increased in CRF reflecting
      the severity of disease. OBJECTIVES: In the present study, we aimed to
      investigate whether blood NGAL level plays a role in the differential diagnosis
      of acute and chronic renal failure. PATIENTS AND METHODS: This was a prospective
      case-control study. Fifty patients presented to emergency department with acute
      renal failure (ARF), 30 with chronic renal failure (CRF) and 20 healthy
      individuals as control group were included in this study. Blood pH, HCO3(-), BUN,
      creatinine and potassium values were evaluated in all patients. Blood NGAL values
      were evaluated in all groups. BUN, serum creatinine and NGAL values were
      statistically compared between patients and controls. RESULTS: Median NGAL levels
      in patients was 304.50 (29), and 60 (0) in control, which was statistically
      significant between the two groups (Z = -6.477, P < 0.001). The median NGAL
      values were 261.50 +/- 291 in ARF group and 428.50 +/- 294 in CRF group. There
      was a significant difference in NGAL level between ARF and CRF groups (Z = -2.52,
      P = 0.012). Median BUN values were 153.46 +/- 82.47 in ARF group and 169.40 +/-
      93.94 in CRF group. There was no significant difference in BUN value between ARF
      and CRF groups (P > 0.05). Median creatinine values were 2.84 +/- 2.95 in ARF
      group and 4.78 +/- 4.32 in CRF group. In serum creatinine values, a significant
      difference was found between ARF and CRF groups (P < 0.05). CONCLUSIONS: Serum
      NGAL levels of ARF and CRF patients were significantly higher than healthy
      individuals. In addition, NGAL values of patients with CRF were significantly
      higher than those of ARF. Serum NGAL values can be used to detect renal injury
      and differentiate ARF and CRF.

PMID- 25389481
TI  - The effects of inhalation aromatherapy on anxiety in patients with myocardial
      infarction: a randomized clinical trial.
AB  - BACKGROUND: Anxiety is an important mental health problem in patients with
      cardiac disease. Anxiety reduces patients' quality of life and increases the risk
      of different cardiac complications. OBJECTIVES: The aim of this study was to
      investigate the effects of inhalation aromatherapy on anxiety in patients with
      myocardial infarction. PATIENTS AND METHODS: This was a randomized clinical trial
      conduced on 68 patients with myocardial infarction hospitalized in coronary care
      units of a large-scale teaching hospital affiliated to Kashan University of
      Medical Sciences, Kashan, Iran in 2013. By using the block randomization
      technique, patients were randomly assigned to experimental (33 patients receiving
      inhalation aromatherapy with lavender aroma twice a day for two subsequent days)
      and control (35 patients receiving routine care of study setting including no
      aromatherapy) groups. At the beginning of study and twenty minutes after each
      aromatherapy session, anxiety state of patients was assessed using the
      Spielberger's State Anxiety Inventory. Data was analyzed using SPSS v. 16.0. We
      used Chi-square, Fisher's exact, independent-samples T-test and repeated measures
      analysis of variance to analyze the study data. RESULTS: The study groups did not
      differ significantly regarding baseline anxiety mean and demographic
      characteristics. However, after the administration of aromatherapy, anxiety mean
      in the experimental group was significantly lower than the control group.
      CONCLUSIONS: Inhalation aromatherapy with lavender aroma can reduce anxiety in
      patients with myocardial infarction. Consequently, healthcare providers,
      particularly nurses, can use this strategy to improve postmyocardial infarction
      anxiety management.

PMID- 25389482
TI  - Association of psychologic and nonpsychologic factors with primary dysmenorrhea.
AB  - BACKGROUND: Primary dysmenorrhea seems to be one the most common gynecologic
      condition in women of childbearing age. OBJECTIVES: The aim of this research was
      to evaluate psychologic and nonpsychologic risk factors of primary dysmenorrhea.
      MATERIALS AND METHODS: A cross-sectional study was conducted on medical sciences
      students of Babol University of Medical Sciences. In this study, 180 females with
      dysmenorrhea and 180 females without dysmenorrhea were enrolled. Psychological
      risk factors were evaluated in four domains including affect, social support,
      personality, and alexithymia. Four questionnaires were used to assessed
      aforementioned domains, namely, Social Support Questionnaire (SSQ), depression,
      anxiety, stress (DAS-21), 20-item Toronto Alexithymia Scale (TAS-20), and NEO
      Five Factor Inventory of Personality (NEO-FFI). In addition, nonpsychologic
      factors were evaluated in three domains including demographic characteristics,
      habits, and gynecologic factors. Data were analyzed using the chi2 test and
      multiple logistic regression analysis. RESULTS: The strongest predictor of
      primary dysmenorrhea was low social support (OR = 4.25; 95% CI, 2.43-7.41). Risk
      of dysmenorrhea was approximately 3.3 times higher in women with alexithymia (OR
      = 3.26; 95% CI, 1.88-5.62), 3.1 times higher in women with menstrual bleeding
      duration >= 7 days (OR = 3.06; 95% CI, 1.73-5.41), 2.5 times higher in women with
      a neurotic character (OR = 2.53; 95% CI, 1.42-4.50), 2.4 times higher in women
      with a family history of dysmenorrhea (OR = 2.43; 95% CI, 1.42-4.50), and twice
      higher in women with high caffeine intake (OR = 1.97; 95% CI, 1.09-3.59).
      CONCLUSIONS: Low social support, alexithymia, neuroticism trait, long menstrual
      bleeding, family history of dysmenorrhea, and high-caffeine diet are important
      risk factors for women with primary dysmenorrhea. This study recommended
      considering psychologic factors as an adjuvant to medical risks in evaluation and
      treatment of primary dysmenorrhea.

PMID- 25389483
TI  - Aspirin and preeclampsia prevention in patients with abnormal uterine artery
      blood flow.
AB  - BACKGROUND: Preeclampsia is one of the leading causes of maternal mortality and
      morbidity. Its prevalence varies between 10-25% among high-risk pregnant
      patients. OBJECTIVES: The aim of this study was to determine whether treatment
      with acetylsalicylic acid (ASA) reduces the incidence of preeclampsia among
      pregnant women with abnormal uterine artery flow. PATIENTS AND METHODS: In this
      double-blind, placebo controlled trial, 80 high-risk pregnant women with
      preeclampsia, who had abnormal findings on Doppler ultrasonography at 12-16 weeks
      of pregnancy (unilateral notch with RI >= 0.65 or bilateral notch with RI >=
      0.55), were randomly divided into two groups; the intervention group was treated
      with ASA tablet 80 mg, one tablet per day, and the control group was given
      placebo. Then patients were followed until the end of their pregnancy period, and
      pregnancy outcomes, including development of preeclampsia, the intrauterine
      growth retardation (IUGR), prematurity, type of delivery, birth weight, and Apgar
      score at one and five minutes were assessed. Data were analyzed using the
      student's t-test, chi-square or Fisher's exact test, and multivariate logistic
      regression. P values less than 0.05 were considered statistically significant.
      RESULTS: There were no significant differences between the two groups in terms of
      baseline characteristics. There was a significant difference between the ASA and
      placebo groups in the incidence of preeclampsia (2.5% versus 22.5%), adjusting
      for the neonatal and maternal covariates. CONCLUSIONS: ASA prophylaxis can be
      used for prevention of preeclampsia in high-risk patients with abnormal uterine
      artery.

PMID- 25389484
TI  - Comparison of neurofeedback and transcutaneous electrical nerve stimulation
      efficacy on treatment of primary headaches: a randomized controlled clinical
      trial.
AB  - BACKGROUND: Headache is one of the most prevalent investigated complaints in the
      neurology clinics and is the most common pain-related complaint worldwide. Stress
      is a significant factor that causes and triggers headaches. Since healthcare
      practitioners experience a lot of stress in their careers, they are more prone to
      headaches. OBJECTIVES: This study was designed to evaluate and compares the
      efficacy of neurofeedback behavioural therapy (NFB) and transcutaneous electrical
      nerve stimulation (TENS) in the treatment of primary headaches in healthcare
      providers. PATIENTS AND METHODS: The current study was a clinical trial,
      performed in Teheran, IR Iran, with two experimental groups and a control group.
      Convenient sampling method was used to recruit patients. Independent variables
      were NFB and TENS and dependent variables were frequency, severity, and duration
      of headache. Blanchard headache diary was used for assessment. Hence, 45
      healthcare providers with primary headache were selected and randomly allocated
      to one of the NFB, TENS, and control groups by block random assignment method.
      All three groups completed the headache diary during one week before and after
      the treatment period as pretest and posttests, respectively. The NFB group was
      treated in the period between pretest and posttest with fifteen 30-minute
      treatment sessions three times a week and the TENS group was treated with fifteen
      20-minute daily sessions. The control group received none of these treatments.
      RESULTS: The results from the analysis of covariance showed that treatment with
      NFB and TENS had caused significant decrease in the frequency, severity, and
      duration of headache in experimental groups. The results of the LSD post-hoc test
      indicated that there were significant differences in the frequency, severity, and
      duration of pain among experimental groups and the control group. Moreover, there
      were significant differences between pain frequencies in experimental groups.
      CONCLUSIONS: According to the results and given the significant reductions in the
      frequency, severity, and duration of headaches, it seems that NFB and TENS might
      have an effective role in reducing primary headaches of healthcare providers. In
      addition, comparing the two methods, treatment with NFB was more effective in
      reducing headache frequency and severity.

PMID- 25389485
TI  - Behavioral prevention regarding sexually transmitted infections and its
      predictors in women.
AB  - BACKGROUND: Sexually transmitted infections (STIs) have a major negative impact
      on sexual and reproductive health globally. The most effective way to avoid STIs
      is to abstain from sexual contact or having sex only in a long-term, mutually
      monogamous relationship with an uninfected partner. OBJECTIVES: This study aimed
      to determine behavioral prevention regarding STIs. PATIENTS AND METHODS: This
      analytic cross-sectional study was performed on 584 women aged 15-49 referring to
      health care centers of Tabriz-Iran in 2013 through multistage cluster sampling.
      Data collecting tool was a questionnaire which its validity and reliability were
      determined previously. Descriptive and inferential statistics (independent T
      test, One-way ANOVA, and univariate and multivariate analyses) were used to
      analyze the data using SPSS 17. P < 0.05 was considered significant. RESULTS: The
      mean +/- SD score of behavioral prevention was 20.57 +/- 2.8 ranging from 0 to
      24. The weakest behavioral prevention was lack of consistent use of condom by
      husband during sex. The mean +/- SD score of individuals' awareness about STIs
      was as low as 17.08 +/- 7.42. Multivariate analysis adjusting potential
      confounders showed a significant association between behavioral prevention and
      awareness, education, sex only with husband, anal, oral, and anal-oral sex.
      CONCLUSIONS: Prevention and care of sexually transmitted diseases are
      interventions able to promote public health. It is necessary to solve different
      factors affecting rapid spread of STDs and their transmission through an
      effective behavioral preventive plan.

PMID- 25389486
TI  - The effect of health promoting intervention on healthy lifestyle and social
      support in elders: a clinical trial study.
AB  - BACKGROUND: Many of the problems pertaining to old age originate from unhealthy
      lifestyle and low social support. Overcoming these problems requires precise and
      proper policy-making and planning. OBJECTIVES: The aim of the current research is
      to investigate the effect of health promoting interventions on healthy lifestyle
      and social support in elders. PATIENTS AND METHODS: This study was conducted as a
      clinical trial lasting for 12 months on 464 elders aged above 60 years who were
      under the aegis of health homes in Tehran, Iran. Participants were selected
      through double stage cluster sampling and then divided into intervention and
      control groups (232 individuals in each). Tools for gathering data were a
      demographic checklist and two standard questionnaires called Health-Promoting
      Lifestyle Profile version 2 and personal resource questionnaire part 2. Data were
      analyzed using descriptive and analytical tests including paired t test, analysis
      of covariance (ANCOVA) and Pearson correlation coefficient. RESULTS: The average
      age of elders in this study was 65.9 +/- 3.6 years (ranging between 60 and 73
      years old). Results showed that the differences between the mean post-test scores
      of healthy lifestyle and its six dimensions as well as perceived social support
      and its five dimensions in the control and intervention groups were statistically
      significant (P value < 0.0001). CONCLUSIONS: Aging is an inevitable stage of
      life. However, effective health promoting interventions can procrastinate it,
      reduce its consequences and problems, and turn it into a pleasant and enjoyable
      part of life.

PMID- 25389487
TI  - The experiences of "difficult life" in heart valve replaced patients.
AB  - BACKGROUND: Several reports, however, not comprehensive, have been presented
      about the experiences of patients with replaced heart-valve. OBJECTIVES: This
      study explores the experiences of the patients with heart valve replacement.
      PATIENTS AND METHODS: A qualitative research with a content analysis approach was
      carried out on the patients with cardiac valve replacement during the year 2012
      and 2013. A purposeful sampling using a semi-structured interview and open-ended
      questions (with the main question of "What problems did you have after the valve
      replacement?" followed by the exploratory questions) were performed until the
      data saturation. All interviews were recorded, then transcribed and typed. The
      data analysis was done according to Grancheim and Lundmen content analysis using
      the MAXQDA software. RESULTS: Of 22 interviews taken from 13 participants, 430
      codes were taken. Out of them, after deleting the similar items, 162 initial, 18
      subcategory, and 5 subsidiary themes (problematic exposure with valve
      replacement, continuity of some difficulties, aggravation of life problems,
      insufficient support, and following a perceived care) were extracted. Based on
      the abstract and deep perception of the categories, the main theme of "difficult
      life" was explored. CONCLUSIONS: Aggravation and the continuity of some physical
      problems, and insufficient support after the valve replacement make the life
      difficult for the patients. Identification of these problems is necessary for
      planning and improvement of the patients' care, life quality, and survival
      through consultations, rehabilitation and education.

PMID- 25389488
TI  - Comorbidity and pattern of substance use in hospitalized psychiatric patients.
AB  - BACKGROUND: Substance use in patients with psychiatric disorder is an every-day
      seen. Detection of this comorbidity can significantly affect the treatment of
      these disorders, as well as substance use. OBJECTIVES: This study has been
      conducted to determine the prevalence and pattern of substance use in
      hospitalized psychiatric patients. PATIENTS AND METHODS: In this cross-sectional
      study, 210 hospitalized psychiatric patients were selected by simple
      randomization from all records of hospitalized patients. The instrument of
      gathering data was a demographic checklist including age, gender, marital status,
      education, type of disorder and substance abuse and duration of psychiatric
      disorder. Data were analyzed by SPSS version 16 using Fisher exact and Chi square
      tests. RESULTS: The mean age of patients was 37.9 years. Most of the patients
      were male, married and unemployed. The Prevalence of substance use was 36.7%. The
      most prevalent pattern of substance use was opium, opioid, methamphetamines and
      other substances (poly substance). The prevalence of substance use in patients
      with mood disorders was more than the other disorders and the most prevalent
      substance use in these patients was opium and opioid. Poly substance use was the
      most prevalent pattern of use (80 %) in psychotic and mood disorders due to
      substance. Significant difference was seen between genders, marital status,
      occupation, duration of illness and frequency of substance use (P < 0.05 ),
      however no significant difference was seen between educational levels, age and
      substance use. CONCLUSIONS: The patients with mood disorders had the highest
      comorbidity with substance use and concurrent use of poly substance was the most
      prevalent pattern of use in these patients. Therefore, successful treatment of
      psychiatric disorders and substance use needs multimodal and more serious
      interventions. Regarding to the pattern of poly substance use in these patients,
      careful screening should be performed at admission.

PMID- 25389489
TI  - Comparing the effect of two educational programs on the quality of life of
      hemodialysis patients in iran.
AB  - BACKGROUND: Various researchers have shown that the health level, performance
      status, and quality of life (QOL) are often less than expected especially in
      hemodialysis (HD) patients. OBJECTIVES: This study aimed to determine the effect
      of the two methods of educational programs on health- related QOL (HRQOL) in
      Iranian HD patients. PATIENTS AND METHODS: In this quasi-experimental, pretest
      posttest interventional study, we employed each subject as his/her own control.
      The study was conducted at the dialysis units in three major general hospitals
      affiliated with Ahvaz Jundishapur University of Medical Sciences. A total of 90
      HD patients were randomly allocated to two 45-patient groups of oral and video
      education programs, respectively. The educational programs included dietary and
      fluid regimens, the care of fistula and skin, and stress management. HRQOL was
      assessed in both groups using a Farsi version of the Short Form Health Survey (SF
      36) before and after the educational programs. Repeated measures analysis of
      variance and ANOVA were used for data analysis through SPSS. RESULTS: SF-36
      domains of physical functioning (P < 0.021), role physical (P < 0.031), social
      functioning (P < 0.001) and mental health (P < 0.001) were significantly
      increased in both oral and vide education groups after the interventions. There
      was no difference in the effectiveness of the two educational programs.
      CONCLUSIONS: Appropriate interventions may potentially lead to improvement in the
      HRQOL of these patients. Therefore, video education as an effective, inexpensive,
      simple, and attractive method is recommended for HD patients.

PMID- 25389490
TI  - Effects of wheat germ extract on the severity and systemic symptoms of primary
      dysmenorrhea: a randomized controlled clinical trial.
AB  - BACKGROUND: Primary dysmenorrhea is one of the most common disorders in women and
      the main cause of absenteeism from work and school. OBJECTIVES: Considering the
      anti-inflammatory properties of wheat germ, the present study examined the
      effects of wheat germ extract on the severity and systemic symptoms of primary
      dysmenorrhea. PATIENTS AND METHODS: This triple-blinded clinical trial was
      performed on 80 employed women in hospitals affiliated with Hamadan University of
      Medical Sciences (Hamadan, IR Iran). Subjects were allocated to two groups of 45
      patients. Three 400-mg capsules of wheat germ extract or placebo were used daily,
      between the 16th day of the menstrual cycle to the fifth day of the next
      menstrual cycle for two consecutive months. Pain intensity was measured by a
      visual analogue scale thrice a day and a four-point verbal rating scale was
      employed to assess systemic symptoms. RESULTS: Pain severity decreased only in
      the wheat germ extract group (P < 0.001) and there was no statistically
      significant change in the placebo group. In the wheat germ extract group, the
      pain severity decreased from 4.701 at baseline to 1.120 at the second cycle. The
      reduction in total scores of systemic symptoms of dysmenorrhea was statistically
      significant only in the wheat germ extract group (P < 0.001) and there was not a
      statistically significant change in the placebo group. It revealed statistically
      significant differences in systemic symptoms associated with dysmenorrhea
      including fatigue, headache, and mood swings in experimental group. CONCLUSIONS:
      Wheat germ extract seems to be an effective treatment for dysmenorrhea and its
      systemic symptoms, probably because of its anti-inflammatory effects.

PMID- 25389491
TI  - Impact of maternal hemoglobin concentration on fetal outcomes in adolescent
      pregnant women.
AB  - BACKGROUND: Studies on the association between maternal hemoglobin (Hb)
      concentration and adverse pregnancy outcome have been inconsistent. Many studies
      have shown the impact of Hb concentration on pregnancy outcomes in adult women;
      however, it is not revealed in adolescent pregnant women. OBJECTIVES: The aim of
      this study was to examine the effect of Hb concentration on birth outcomes in
      pregnant adolescents as a high-risk group. PATIENTS AND METHODS: In this cross
      sectional study, 312 healthy and nonsmoker adolescent pregnant women with
      gestational age (GA) of 37-40 weeks were chosen by random sampling, and were
      followed until delivery. A complete history was obtained from women. In addition,
      clinical examination and Hb test were performed. After birth, the associations
      between Hb concentration during pregnancy and birth outcomes were investigated.
      Statistical analyses were performed using SPSS software by t-test, chi-square and
      ANOVA. RESULTS: In total, about 23.2 % were anemic, 58% had normal level of Hb
      (11-13.2 g/dL) and 18.8% had Hb > 13.2 g/dL. The mean birth weight was 3197.8 +/-
      398.25 grams and it was more in mothers with Hb = 10.5-12.5 g/dL than others (Hb
      < 10.5 or Hb > 12.5 g/dL) (P < 0.001). The lowest mean birth weight was found in
      mothers with Hb < 10.5 (3033.33 +/- 422). Moreover, the mean birth weight of male
      newborns was more than females (P = 0.001). Eight percent of neonates had Apgar
      score less than eight. Low Apgar score in anemic group and mothers with high Hb
      concentration (Hb > 12.5 g/dL) was more than others. CONCLUSIONS: Abnormal Hb
      concentrations increase the risk of adverse birth outcomes such as low birth
      weight (LBW) and low Apgar scores in pregnant adolescents, so intensive care is
      recommended for this group of pregnant women.

PMID- 25389492
TI  - Immediate and delayed effects of forearm kinesio taping on grip strength.
AB  - BACKGROUND: Due to the fundamental role of gripping in most upper limb
      activities, grip strength promotion is a chief goal in the treatment of patients
      with upper limb musculoskeletal disorders. Kinesio taping is a novel and
      effective therapeutic technique believed to facilitate muscle contraction through
      stimulating mechanoreceptors and increasing the sensory feedback around the taped
      region. OBJECTIVES: The present study aimed to identify the best region (flexor,
      extensor and flexor/extensor regions) and time (immediate, 0.5, 1, 1.5, and 2
      hours) of forearm Kinesio taping to obtain the maximum improvement in grip
      strength. MATERIALS AND METHODS: In this longitudinal study, 40 healthy men and
      women (the mean age of 22.3 +/- 2.19 years) were selected among students of
      Shahid Beheshti University of Medical Sciences, Tehran, Iran by simple, nonrandom
      sampling method. A dynamometer was used to measure grip strength immediately and
      every 30 minutes during the two hours after I-shaped application of tape (with
      50% stretch) to the flexor, extensor, and flexor/extensor forearm muscles.
      RESULTS: Grip strength was significantly increased in various muscle groups for
      males (P = 0.002) and females (P = 0.000) of the forearm and at different
      intervals for males (P = 0.000) and females (P = 0.000). Moreover, in both men
      and women, tape application to the extensor region provided greater grip strength
      compared to taping of the flexor and flexor/extensor regions (P = 0.000 for
      both). Furthermore, the maximum increase in grip strength were 0.5 (10.8%
      increase, P = 0.001) and 1.5 h (23.9% increase, P = 0.000) after taping in males
      and females, respectively. CONCLUSIONS: Taping the extensor region of forearm is
      recommended to achieve higher grip strength. Although grip strength increased at
      a slower pace in females than males, the final values were higher in women.

PMID- 25389493
TI  - Factors affecting intensive care units nursing workload.
AB  - BACKGROUND: The nursing workload has a close and strong association with the
      quality of services provided for the patients. Therefore, paying careful
      attention to the factors affecting nursing workload, especially those working in
      the intensive care units (ICUs), is very important. OBJECTIVES: This study aimed
      to determine the factors affecting nursing workload in the ICUs of the hospitals
      affiliated to Tehran University of Medical Sciences. MATERIALS AND METHODS: This
      was a cross-sectional and analytical-descriptive study that has done in Iran. All
      nurses (n = 400) who was working in the ICUs of the hospitals affiliated to
      Tehran University of Medical Sciences in 2014 were selected and studied using
      census method. The required data were collected using a researcher-made
      questionnaire which its validity and reliability were confirmed through getting
      the opinions of experts and using composite reliability and internal consistency
      (alpha = 0.89). The collected data were analyzed through exploratory factor
      analysis (EFA), confirmatory factor analysis (CFA) and using SPSS 18.0 and AMOS
      18.0. RESULTS: Twenty-five factors were divided into three major categories
      through EFA, including structure, process, and activity. The following factors
      among the structure, process and activity components had the greatest importance:
      lack of clear responsibilities and authorities and performing unnecessary tasks
      (by a coefficient of 0.709), mismatch between the capacity of wards and the
      number of patients (by a coefficient of 0.639), and helping the students and
      newly employed staff (by a coefficient of 0.589). CONCLUSIONS: The nursing
      workload is influenced by many factors. The clear responsibilities and
      authorities of nurses, patients' admission according to the capacity of wards,
      use of the new technologies and equipment, and providing basic training for new
      nurses can decrease the workload of nurses.

PMID- 25389495
TI  - The prevalence of zinc deficiency in patients with thalassemia in South East of
      iran, sistan and baluchistan province.
AB  - BACKGROUND: There are different and controversial reports about zinc deficiency
      in patients with major thalassemia. OBJECTIVES: The aim of this study was to
      evaluate zinc status in patients with major thalassemia in Sistan and Baluchistan
      province, southeastern Iran. PATIENTS AND METHODS: The study was performed in Ali
      Asghar Hospital, a specialized governmental hospital located in Zahedan, Iran. In
      this cross-sectional study, 369 patients with a history of major thalassemia for
      more than 5 years entered the study using convenience sampling method. Thirty-six
      subjects were excluded from the study based on our exclusion criteria. Zinc level
      was measured in all patients after 12 hours fasting using atomic absorption
      spectrometry method in 2012. RESULTS: Of 369 cases, 333 patients were eligible
      and evaluated. The mean age was 15.63 +/- 7.4 years. One hundred ninety two cases
      were male and others were female (141 cases). About 27% (90) of the cases were 5
      10 years-old, 24% (80) were 10-15 years-old and 49% were older than 15 years old.
      Iron chelator in 65.46% was Desferrioxamine, in 28.2% was Deferasirox and in
      19.5% was combination of Desferrioxamine and Deferiprone. All cases had zinc
      deficiency, and 98.5% had severe zinc deficiency. Others (1.5%) had mild
      deficiency. CONCLUSIONS: Our study on 333 patients with major thalassemia
      documented severe zinc deficiency in all cases. We had no cases with normal or
      increased zinc levels. It was different with other reports in the world.

PMID- 25389494
TI  - The Effect of Group Discussion on the Quality of Life and HbA1c Levels of
      Adolescents With Diabetes.
AB  - BACKGROUND: Diabetes is a metabolic syndrome and the most common endocrine
      disorder in childhood and adolescence. Diabetes occurs at any age but the highest
      outbreak is during ten to 15 years of age and 75% of the cases are diagnosed at
      the age 18. OBJECTIVES: This study aimed to investigate the effect of a group
      discussion on the quality of life (QOL) and glycosylated hemoglobin A (HbA1c)
      levels of adolescents with diabetes. PATIENTS AND METHODS: This quasi
      experimental study was performed on 56 adolescents with diabetes who were
      referred to Golabchi Diabetes Center in Kashan, Iran. After obtaining written
      informed consent from the patients, blood sample was drawn for measuring sugar
      and HbA1c levels. The participants completed the questionnaire regarding the QOL.
      Patients were randomly allocated to four groups. All the groups attended similar
      group discussion sessions, which were conducted according to the guidance of
      diabetic specialists. The groups' members followed the discussed instructions for
      four months. Then, another questionnaire was completed and blood sugar and HbA1c
      levels were measured again. The results were compared by paired-samples t-test
      and Wilcoxon signed-rank test. RESULTS: After the group discussion sessions, in
      56% of the patients the HbA1c levels (8.45 +/- 1.35 and 6.98 +/- 0.89 before and
      after intervention, respectively) and QOL were improved significantly. The mean
      age of these patients was 14.75 +/- 1.80 years and the mean of daily insulin
      injection was 35.70 +/- 13.42 units. CONCLUSIONS: Sharing experiences trough
      group discussions and receiving instructive feedbacks can improve the QOL and
      metabolic status of adolescents with diabetes.

PMID- 25389496
TI  - Effects of simvastatin treatment on serum adiponectin concentrations in patients
      with dislipidemia.
AB  - BACKGROUND: Adiponectin is an adipose tissue-derived protein with anti
      inflammatory properties. Statins are a class of cholesterol-lowering drugs,
      widely used for treatment of cardiovascular diseases. OBJECTIVES: In the current
      study, we aimed to assess the effects of simvastatin on serum levels of
      adiponectin in patients with dyslipidemia, recruited from Ghaem Hospital,
      Mashhad, Iran. MATERIALS AND METHODS: A total of 102 patients with dyslipidemia
      were treated with simvastatin or placebo during a double-blind, cross-over,
      placebo-controlled trial. The adiponectin levels were measured before and after
      each treatment period. Seventy seven participants completed the study. RESULTS:
      There was a significant reduction in serum total cholesterol (approxmately 21%),
      low density lipoprotein-cholesterol (LDL-C) (approxmately 28%), and triglycerides
      (approxmately 11%), after four weeks of treatment with simvastatin (P < 0.001).
      CONCLUSIONS: No significant change in serum adiponectin concentrations was
      observed after treatment with simvastatin. This may be because of the relatively
      short duration of treatment and longer treatment duration may be necessary to
      investigation in future studies.

PMID- 25389497
TI  - Camurati-engelmann disease association with hypogonadism and primary
      hypothyroidism.
AB  - INTRODUCTION: Camurati-Engelmann disease (CED) is a rare autosomal dominant
      disease with various phenotypic expressions. The symptoms usually develop during
      childhood. The hallmark of the disease is bilateral symmetric diaphyseal
      hyperostosis of the long bones with progressive involvement of the metaphysis.
      The epiphysis is strictly spared. The common clinical symptoms are pain of the
      extremities, muscle wasting, waddling gait, and lethargy. CED is rarely seen in
      conjunction with hypogonadism. CED-associated hypothyroidism has not been
      reported yet. Clinical assessment and skeletal survey are important to make the
      diagnosis. CASE PRESENTATION: Hereby we reported a case of CED with concomitant
      hypogonadism and hypothyroidism. Serial plain radiographs of the patient showed
      classic and progressive diaphyseal cortical hyperostosis of the long bone.
      CONCLUSIONS: Hyperostosis of the skull was observed in the present case. The
      characteristic osseous changes of CED were highlighted and the differential
      diagnoses were discussed.

PMID- 25389498
TI  - Giant fibroadenoma growing rapidly during pregnancy.
AB  - INTRODUCTION: Giant fibroadenoma is a rare disease with unknown etiology. During
      pregnancy, fibroadenomas increase in size and may show lactational histologic
      changes. High concentrations of estrogen, progesterone, and prolactin promote the
      ductal growth and formation of tubuloalveolar structures. This may be a reason
      for the significant enlargement in this period. CASE PRESENTATION: We presented a
      case of giant fibroadenoma, first detected at the onset of pregnancy, which grew
      rapidly and was excised surgically two months after the birth. There was no
      marked deformity in the breast nor a need to reconstruct it, despite the giant
      mass was excised and the mother was lactating. DISCUSSION: We presented a rare
      case of giant fibroadenoma in a lactating woman. A progressively growing mass in
      breast can lead to structural damages. The current management approach for giant
      fibroadenomas is still surgical excision.

PMID- 25389499
TI  - Hypertension Subtypes among Hypertensive Patients in Ibadan.
AB  - Background. Certain hypertension subtypes have been shown to increase the risk
      for cardiovascular morbidity and mortality and may be related to specific
      underlying genetic determinants. Inappropriate characterization of subtypes of
      hypertension makes efforts at elucidating the genetic contributions to the
      etiology of hypertension largely vapid. We report the hypertension subtypes among
      patients with hypertension from South-Western Nigeria. Methods. A total of 1858
      subjects comprising 76% female, hypertensive, aged 18 and above were recruited
      into the study from two centers in Ibadan, Nigeria. Hypertension was identified
      using JNCVII definition and was further grouped into four subtypes: controlled
      hypertension (CH), isolated systolic hypertension (ISH), isolated diastolic
      hypertension (IDH), and systolic-diastolic hypertension (SDH). Results. Systolic
      diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5%)
      and IDH (4.9% versus 4.7%) were more prevalent among females, ISH (10.1% versus
      6.2%) was higher among males (P = 0.048). Female subjects were more obese (P <
      0.0001) and SDH was prevalent among the obese group. Conclusion. Gender and
      obesity significantly influenced the distribution of the hypertension subtypes.
      Characterization of hypertension by subtypes in genetic association studies could
      lead to identification of previously unknown genetic variants involved in the
      etiology of hypertension. Large-scale studies among various ethnic groups may be
      needed to confirm these observations. 

PMID- 25389501
TI  - Eltrombopag in Good's Syndrome.
AB  - Good's syndrome is a rare acquired immunodeficiency associated with thymoma.
      Eltrombopag is a thrombopoietin receptor agonist and has been shown to be a
      valuable supplement to the treatment of several types of refractory cytopenias.
      In this paper, we describe a male patient suffering from Good's syndrome with
      immune-mediated T-cell driven pancytopenia and absence of megakaryopoiesis. He
      was successfully treated with eltrombopag resulting in a multilineage clinical
      response. 

PMID- 25389500
TI  - Prevalence, correlates, and prognosis of peripheral artery disease in rural
      ecuador-rationale, protocol, and phase I results of a population-based survey: an
      atahualpa project-ancillary study.
AB  - Background. Little is known on the prevalence of peripheral artery disease (PAD)
      in developing countries. Study design. Population-based study in Atahualpa. In
      Phase I, the Edinburgh claudication questionnaire (ECQ) was used for detection of
      suspected symptomatic PAD; persons with a negative ECQ but a pulse pressure >=65
      mmHg were suspected of asymptomatic PAD. In Phase II, the ankle-brachial index
      will be used to test reliability of screening instruments and to determine PAD
      prevalence. In Phase III, participants will be followed up to estimate the
      relevance of PAD as a predictor of vascular outcomes. Results. During Phase I,
      665 Atahualpa residents aged >=40 years were enrolled (mean age: 59.5 +/- 12.6
      years, 58% women). A poor cardiovascular health status was noticed in 464 (70%)
      persons of which 27 (4%) had a stroke and 14 (2%) had ischemic heart disease.
      Forty-four subjects (7%) had suspected symptomatic PAD and 170 (26%) had
      suspected asymptomatic PAD. Individuals with suspected PAD were older, more often
      women, and had a worse cardiovascular profile than those with nonsuspected PAD.
      Conclusions. Prevalence of suspected PAD in this underserved population is high.
      Subsequent phases of this study will determine whether prompt detection of PAD is
      useful to reduce the incidence of catastrophic vascular diseases in the region. 

PMID- 25389502
TI  - 36-year-old female with catastrophic antiphospholipid syndrome treated with
      eculizumab: a case report and review of literature.
AB  - Catastrophic antiphospholipid syndrome (CAPS) is a rare but potentially life
      threatening condition characterized by diffuse vascular thrombosis, leading to
      multiple organ failure developing over a short period of time in the presence of
      positive antiphospholipid antibodies (aPL). CAPS is a severe form of
      antiphospholipid syndrome, developing in about 1% of cases of classic
      antiphospholipid syndrome, manifesting as microangiopathy, affecting small
      vessels of multiple organs. It is acute in onset, with majority of cases
      developing thrombocytopenia and less frequently hemolytic anemia and disseminated
      intravascular coagulation. Lupus anticoagulant and anticardiolipin antibodies
      have been reported as predominant antibodies associated with CAPS. Treatment
      options often utilized in CAPS include anticoagulation, steroids, plasma
      exchange, cyclophosphamide therapy, and intravenous immunoglobulin therapy. Even
      though the reported incidence of this condition is considered to be low, the
      mortality rate is approaching 50%. The high rate of mortality should warrant
      greater awareness among clinicians for timely diagnosis and treatment of this
      life-threatening condition. Studies have shown that complement activation plays a
      key role in the pathogenesis of aPL mediated thrombosis in CAPS. We report a case
      of a 36-year-old female admitted with clinical and laboratory findings consistent
      with CAPS successfully treated with eculizumab, a terminal complement inhibitor. 

PMID- 25389503
TI  - Prenatal diagnosis of a fetus with ring chromosomal 15 by two- and three
      dimensional ultrasonography.
AB  - We report on a prenatal diagnosis of ring chromosome 15 in a fetus with left
      congenital diaphragmatic hernia (CDH) and severe intrauterine growth restriction
      (IUGR). A 31-year-old woman, gravida 2 para 1, was referred because of increased
      nuchal translucency at gestational age of 13 weeks. Comprehensive fetal
      ultrasound examination was performed at 19 weeks revealing an early onset IUGR,
      left CDH with liver herniation, and hypoplastic nasal bone. Three-dimensional
      ultrasound (rendering mode) showed low set ears and depressed nasal bridge.
      Amniocentesis was performed with a result of a 46,XX,r(15) fetus after a
      cytogenetic study. A 1,430 g infant (less than third percentile) was born at 36
      weeks. The infant presented with respiratory failure and died at 2 h of life.
      Postnatal karyotype from the umbilical cord confirmed the diagnosis of 15-ring
      chromosome. We described the main prenatal 2D- and 3D-ultrasound findings
      associated with ring chromosome 15. The interest in reporting the present case is
      that CDH can be associated with the diagnosis of 15-ring chromosome because the
      critical location of the normal diaphragm development is at chromosome 15q26.1
      q26.2. 

PMID- 25389504
TI  - Neonatal pulmonary hemosiderosis.
AB  - Idiopathic pulmonary hemosiderosis (IPH) is a rare complex entity characterized
      clinically by acute or recurrent episodes of hemoptysis secondary to diffuse
      alveolar hemorrhage. The radiographic features are variable, including diffuse
      alveolar-type infiltrates, and interstitial reticular and micronodular patterns.
      We describe a 3-week-old infant presenting with hemoptysis and moderate
      respiratory distress. Idiopathic pulmonary hemosiderosis was the first working
      diagnosis at the Emergency Department and was confirmed, 2 weeks later, by
      histological studies (bronchoalveolar lavage). The immunosuppressive therapy by 1
      mg/kg/d prednisone was immediately started, the baby returned home on steroid
      therapy at a dose of 0,5 mg/kg/d. The diagnosis of idiopathic pulmonary
      hemosiderosis should be evocated at any age, even in the neonate, when the
      clinical presentation (hemoptysis and abnormal radiological chest images) is
      strongly suggestive. 

PMID- 25389505
TI  - Multicentric spinal tuberculosis with sternoclavicular joint involvement: a rare
      presentation.
AB  - Background. Tuberculosis is a chronic disease which may have varied
      presentations. Though pulmonary tuberculosis is the commonest, extrapulmonary
      tuberculosis involving skeletal system is often seen. Individuals with poor
      nourishment and immunological status are especially susceptible for disseminated
      and multicentric tuberculosis. Case Report. We here present a case of
      tuberculosis involving multiple anatomical locations in an immune-competent
      patient which was diagnosed with radiological studies and confirmed with
      histological examination. Patient was put on multidrug antitubercular therapy and
      responded well to the treatment with improvement in clinical and radiological
      picture. Clinical Relevance. This report of a rare case makes us aware of the
      varied presentations which tuberculosis can present with. It should be kept as a
      differential diagnosis in patients with cough and fever but not responding to
      conventional treatment. This is even more important in countries with poor
      socioeconomic conditions. 

PMID- 25389506
TI  - Pulmonary Mycobacterium kansasii Infection Mimicking Malignancy on the (18)F-FDG
      PET Scan in a Patient Receiving Etanercept: A Case Report and Literature Review.
AB  - A 66-year-old male presented with chest pain, malaise, generalized weakness, and
      weight loss. He had been receiving etanercept injection for rheumatoid arthritis.
      Chest X-ray revealed a right upper lobe mass. Chest computed tomography (CT)
      showed a right apical mass, highly suggestive of a Pancoast tumor. The thoracic
      fluorine-18 fluoro-deoxy-glucose ((18)F-FDG) positron emission tomography (PET)
      scan demonstrated significantly high metabolic pulmonary lesions with the
      standardized uptake value (SUV) of 12.5, consistent with lung cancer. The patient
      underwent bronchoscopy and bronchoalveolar lavage (BAL). BAL cytology was
      negative for malignant cells. BAL acid fast bacilli (AFB) smears were positive,
      and Mycobacterium kansasii was eventually isolated. He received a 12-month course
      of rifampin, isoniazid, and ethambutol. Interval resolution of pulmonary lesions
      was noted on follow-up serial CT chest studies. There has been increasing
      incidence of nontuberculous mycobacterial infections reported in patients treated
      with the antitumor necrosis factor-alpha (anti-TNF-alpha) agents. Infectious foci
      have an increased glucose metabolism which potentially causes a high FDG uptake
      on the (18)F-FDG PET scan, leading to undue anxiety and cost to the patients.
      This is the first reported case of pulmonary M. kansasii infection with a
      positive thoracic (18)F-FDG PET study mimicking malignancy in a patient on
      etanercept. 

PMID- 25389507
TI  - Methicillin-Resistant Staphylococcus aureus Prostatic Abscess in a Liver
      Transplant Recipient.
AB  - Prostatic abscesses are usually related to gram-negative bacilli. However,
      methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a substantial
      cause of prostatic abscesses in recent years. Herein, we report the case of a 31
      year-old man with a history of orthotopic liver transplantation 10 years ago who
      presented with acute onset dysuria and abdominal pain and was diagnosed with a
      MRSA prostatic abscess. To our knowledge, this is the first case describing a
      prostatic abscess in a liver transplant recipient and the first reporting MRSA as
      the causative organism of a prostatic abscess in a solid organ transplant
      recipient. 

PMID- 25389508
TI  - Roll the dice.

PMID- 25389509
TI  - Molecular Investigation of Quinolone Resistance of Quinolone Resistance
      Determining Region in Streptococcus pneumoniae Strains Isolated from Iran Using
      Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Method.
AB  - OBJECTIVES: The resistance of Streptococcus pneumoniae to the recently available
      antibiotic treatment has been a growing problem. The aim of the study was to
      determine the quinolone-resistant strains and detect the presence of mutations in
      the quinolone resistance-determining regions of the gyrA, parE, and parC genes.
      METHODS: In this study, for the first time in Iran, the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method was used to
      investigate the presence of mutations at quinolone resistance-determining regions
      of topoisomerase IV and DNA gyrase on 82 S. pneumoniae strains, among them 45
      clinical samples were from patients and 37 from healthy carriers (control group).
      RESULTS: In clinical samples, 34 (75.56%) strains contained mutations in the parC
      gene, 31 (68.89%) carried mutations in the gyrA gene, and 14 (31.11%) had parE
      gene mutations. Antibiotic susceptibility test was performed using the CLSI
      (Clinical and Laboratory Standards Institute) criteria on three different
      generations of quinolone family, with nalidixic acid (82.22%) showing the highest
      resistance and levofloxacin (42.22%) the least resistance. CONCLUSION: Results
      indicated that there is a significant correlation between quinolone resistance
      development and mutations in the parE gene as well as in the parC and gyrA genes.

PMID- 25389510
TI  - Associations between estimated desaturase activity and insulin resistance in
      korean boys.
AB  - OBJECTIVES: Obesity in childhood increases the risk of obesity in adulthood, and
      is predictive of the development of metabolic disorders. The fatty acid
      compositions of various tissues, including blood, are associated with obesity and
      obesity-associated disorders. Thus, tracking plasma phospholipid (PL) features
      and metabolic parameters in young individuals may strengthen the utility of fatty
      acid composition as an early biomarker of future metabolic disorders. METHODS:
      Anthropometric and blood biochemical data were obtained from 131 Korean males
      aged 10.5 +/- 0.4 years, and followed up at 2 years. We analyzed the plasma PL
      fatty acids according to obesity. Obese children were defined as those with a
      body mass index (BMI) greater than the 85(th) percentile for age and gender,
      based on Korean child growth standards. RESULTS: Activities of lipid desaturases,
      stearyl-CoAD (SCD-16,16:1n-7/16:0), delta-6D (D6D, 20:3n-6/18:2n-6), and delta-5D
      (D5D, 20:4n-6/20:3n-6), were estimated. Obese individuals had significantly
      higher proportions of palmitoleic acid (16:1n-7) and dihomo-gamma linolenic acid
      (DGLA, 20:3n-6) at both baseline and follow-up than did lean individuals. The
      activities of SCD-16 and D6D were higher in obese than lean boys. The baseline
      SCD-16 activity level was positively associated with the baseline waist
      circumference (WC) and the metabolic risk score. The baseline D6D level was
      positively associated with WC and also with the homeostasis model of assessment
      of insulin resistance (HOMA-IR), a surrogate marker of insulin resistance (IR),
      and metabolic risk score at both baseline and follow-up. CONCLUSION: In young
      Korean males, higher D6D activity predicts the future development of IR and
      associated metabolic disorders including dyslipidemia.

PMID- 25389511
TI  - Suicidal Ideation and its Correlates among Juvenile Delinquents in South Korea.
AB  - OBJECTIVES: This study investigated suicidal ideation and its correlates among
      juvenile delinquents in South Korea. METHODS: Suicidal ideation, psychological
      health status, and health-related behaviors were assessed using a self
      administered questionnaire in 1682 juvenile offenders aged between 15 and 18
      years in 2012. RESULTS: The prevalence of suicidal ideation in juvenile
      delinquents was 15.2%. Girls were more likely to report suicidal thoughts than
      boys (30.3% vs. 12.7%). Suicidal ideation was more common among adolescents who
      were not living with their family prior to entering detention centers (22.6% vs.
      13.2%) than their counterparts. The likelihood of suicidal ideation was
      significantly associated with problem drinking [odds ratio (OR) = 1.84],
      psychedelic drug use (OR = 2.04), feeling unhappy (OR = 3.05), feeling sad or
      depressed (OR = 13.37) after controlling for sociodemographic factors, other
      health behaviors and perceptions. CONCLUSION: The present study provides evidence
      for an association between suicidal ideation and psychological health and health
      risk behaviors among juvenile delinquents. It also highlights the importance of
      mental health and behavioral interventions for this population to prevent
      suicidality.

PMID- 25389512
TI  - Optimal implementation of intervention strategies for elderly people with
      ludomania.
AB  - OBJECTIVES: Now-a-days gambling is growing especially fast among older adults. To
      control the gratuitous growth of gambling, well-analyzed scientific strategies
      are necessary. We tried to analyze the adequacy of the health of society
      mathematically through immediate treatment of patients with early prevention.
      METHODS: The model from Lee and Do was modified and control parameters were
      introduced. Pontryagin's Maximum Principle was used to obtain an optimal control
      strategy. RESULTS: Optimal control can be achieved through simultaneous use of
      the control parameters, though it varies from society to society. The control
      corresponding to prevention needed to be implemented in full almost all the time
      for all types of societies. In the case of the other two controls, the scenario
      was greatly affected depending on the types of societies. CONCLUSION: Prevention
      and treatment for elderly people with ludomania are the main intervention
      strategies. We found that optimal timely implementation of the intervention
      strategies was more effective. The optimal control strategy varied with the
      initial number of gamblers. However, three intervention strategies were
      considered, among which, preventing people from engaging in all types of gambling
      proved to be the most crucial.

PMID- 25389513
TI  - Cloning and Expression of Recombinant Tick-Borne Encephalitis Virus-like
      Particles in Pichia pastoris.
AB  - OBJECTIVES: The purpose of this study was to verify the feasibility of using the
      glyceraldehyde-3-phosphate dehydrogenase (GAP) promotor based Pichia pastoris
      expression system to produce tick-borne encephalitis virus (TBEV) virus-like
      particles (VLPs). METHODS: The complementary DNA encoding the TBEV prM signal
      peptide, prM, and E proteins of TBEV Korean strain (KrM 93) was cloned into the
      plasmid vector pGAPZalphaA, then integrated into the genome of P. pastoris, under
      the control of the GAP promoter. Expression of TBEV VLPs was determined by
      Western blotting using monoclonal antibody against TBEV envelope (E) protein.
      RESULTS: Recombinant TBEV VLPs consisting of prM and E protein were successfully
      expressed using the GAP promoter-based P. pastoris expression system. The results
      of Western blotting showed that the recombinant proteins were secreted into the
      culture supernatant from the P. pastoris and glycosylated. CONCLUSION: This study
      suggests that recombinant TBEV VLPs from P. pastoris offer a promising approach
      to the production of VLPs for use as vaccines and diagnostic antigens.

PMID- 25389514
TI  - A New Direction of Cancer Classification: Positive Effect of Low-Ranking
      MicroRNAs.
AB  - OBJECTIVES: Many studies based on microRNA (miRNA) expression profiles showed a
      new aspect of cancer classification. Because one characteristic of miRNA
      expression data is the high dimensionality, feature selection methods have been
      used to facilitate dimensionality reduction. The feature selection methods have
      one shortcoming thus far: they just consider the problem of where feature to
      class is 1:1 or n:1. However, because one miRNA may influence more than one type
      of cancer, human miRNA is considered to be ranked low in traditional feature
      selection methods and are removed most of the time. In view of the limitation of
      the miRNA number, low-ranking miRNAs are also important to cancer classification.
      METHODS: We considered both high- and low-ranking features to cover all problems
      (1:1, n:1, 1:n, and m:n) in cancer classification. First, we used the correlation
      based feature selection method to select the high-ranking miRNAs, and chose the
      support vector machine, Bayes network, decision tree, k-nearest-neighbor, and
      logistic classifier to construct cancer classification. Then, we chose Chi-square
      test, information gain, gain ratio, and Pearson's correlation feature selection
      methods to build the m:n feature subset, and used the selected miRNAs to
      determine cancer classification. RESULTS: The low-ranking miRNA expression
      profiles achieved higher classification accuracy compared with just using high
      ranking miRNAs in traditional feature selection methods. CONCLUSION: Our results
      demonstrate that the m:n feature subset made a positive impression of low-ranking
      miRNAs in cancer classification.

PMID- 25389515
TI  - Comparison of four serological tests for detecting antibodies to Japanese
      encephalitis virus after vaccination in children.
AB  - OBJECTIVES: Several different methods are currently used to detect antibodies to
      Japanese encephalitis virus (JEV) in serum samples or cerebrospinal fluid. These
      methods include the plaque reduction neutralization test (PRNT), the
      hemagglutination inhibition (HI) test, indirect immunofluorescence assay (IFA),
      and enzyme-linked immunosorbent assay (ELISA). The purpose of this study was to
      compare the performance of each method in detecting vaccine-induced antibodies to
      JEV. METHODS: The study included 29 children who had completed a primary
      immunization schedule with an inactivated vaccine against JEV derived from mouse
      brain (n = 15) or a live attenuated SA14-14-2 vaccine (n = 14). Serum samples
      were collected between 3 months and 47 months after the last immunization. The
      serum samples were tested by performing the PRNT, HI test, in-house IFA, and
      commercial ELISA. The antibody detection rates were compared between tests.
      RESULTS: All 29 serum samples were positive with the PRNT, showing antibody
      titers from 1:20 to 1:2560. The HI test showed positive rates of 86.7% (13/15)
      and 71.4% (10/14) in the inactivated and live attenuated vaccine groups,
      respectively. The results of the IFA for immunoglobulin (Ig)G were positive in
      53.3% (8/15) of children in the inactivated vaccine group and 35.7% (5/14) in the
      live attenuated vaccine group. Neither the IFA nor ELISA detected JEV IgM
      antibodies in any of the 29 children. CONCLUSION: These results show that
      detection rates of vaccine-induced antibodies to JEV have a wide range (0-100%)
      depending on the testing method as well as the time since immunization and
      individual differences between children. These findings are helpful in
      interpreting serological test results for the diagnosis of Japanese encephalitis
      in situations where vaccines are widely administered.

PMID- 25389516
TI  - Evidence Gap on the Prevalence of Non-conventional Risk Factors for Type 2
      Diabetes in Iran.
AB  - OBJECTIVES: Robust scientific evidence exists about the role of non-conventional
      risk factors in type 2 diabetes worldwide. The current epidemiological pattern of
      the disease in Iran suggests a precipitating role for these non-conventional risk
      factors. This review was performed to examine the research evidence suggesting a
      higher prevalence of non-conventional type 2 diabetes risk factors in Iran.
      METHODS: MeSH keywords were applied to search several databases, including
      PUBMED, MEDLINE, AMED, EMBASE, Iran DOC, and the Scientific Information Database
      without a time limit from inception to September 2011. The quality of the non
      interventional and population-based studies on Iranians included in these
      databases was assessed by the authors and any disagreement was resolved with
      consensus. RESULTS: The literature search yielded 1847 publications, of which 62
      were included in this study after eliminating non-relevant and overlapping
      papers. No study was found that verified a higher prevalence of the non
      conventional type 2 diabetes risk factors in the Iranian population. CONCLUSION:
      The identified evidence gap about the role of prominent non-conventional risk
      factors of type 2 diabetes in the Iranian population could be a major caveat in
      the application of an evidence-based approach to endorse or reject existing
      hypothesis about these risk factors. Studies on the prevalence of non
      conventional biomarkers of type 2 diabetes among Iranians could be a promising
      area of research.

PMID- 25389517
TI  - In Vitro Antibacterial Activity, Gas Chromatography-Mass Spectrometry Analysis of
      Woodfordia fruticosa Kurz. Leaf Extract and Host Toxicity Testing With In Vitro
      Cultured Lymphocytes From Human Umbilical Cord Blood.
AB  - OBJECTIVES: To locate a plant with suitable phytochemicals for use as
      antimicrobial agents to control multidrug-resistant (MDR) bacteria as a
      complementary medicine, without host toxicity as monitored through cultured
      lymphocytes from human umbilical cord blood. METHODS: The methanol crude leaf
      extract of the plant Woodfordia fruticosa was subjected to antimicrobial assay in
      vitro with nine pathogenic MDR bacteria from clinical samples. This was followed
      by bioassay-guided fractionation with seven non-polar to polar solvents, gas
      chromatography-mass spectrometry analysis of the n-butanol fraction, and
      monitoring of the host toxicity of the leaf extract with in vitro grown
      lymphocytes from human umbilical cord blood. RESULTS: The leaf extract of W.
      fruticosa had a controlling capacity for MDR bacteria. The minimum inhibitory
      concentration and minimum bactericidal concentration of the n-butanol fraction
      were < 1.89 mg/mL extract and 9.63 mg/mL extract, respectively. The gas
      chromatography-mass spectrometry spectrum of the n-butanol fraction confirmed the
      presence of 13 peaks of different compounds with retention times of 9.11 minutes,
      9.72 minutes, 10.13 minutes, 10.78 minutes, 12.37 minutes, 12.93 minutes, 18.16
      minutes, 21.74 minutes, 21.84 minutes, 5.96 minutes, 12.93 minutes, 24.70
      minutes, and 25.76 minutes. The six leading compounds were: diethyl phthalate:
      IUPAC name: diethyl benzene-1,2-dicarboxylate; 5-methyl-2-(1-methylethyl) phenol:
      IUPAC name: 5-methyl-2-propan-2-ylphenol; (E )-3,7-dimethylocta-2,6-diene-1
      thiol: IUPAC name: (2Z)-3,7-dimethylocta-2,6-diene-1-thiol; 2,6,10-dodecatrien-1
      ol, 3,7,11-trimethyl-, (E,E ): IUPAC name: 2,6,10-dodecatrien-1-ol; 3,7,11
      trimethyl-, (E,E); 2-methoxy-4-(2-propenyl) phenol: IUPAC name: 2-methoxy-4-[(1E)
      prop-1-en-1-yl]phenol; hexadecanoic acid: IUPAC name: hexadecanoic acid.
      CONCLUSION: The presence of antimicrobial compounds that are therapeutically
      potent against MDR bacteria was confirmed in W. fruticosa. The crude leaf extract
      showed no host toxicity with human lymphocytes; the n-butanol fraction of the
      extract was the most suitable bioactive fraction. The terpenes isolated were: 5
      methyl-2-(1-methylethyl) phenol, 2-methoxy-4-(2-propenyl) phenol, 2,6-octadien-1
      ol, 3,7-dimethyl-(E)-2,6-octadienal, 3,7-dimethylcyclohexanol, and cyclohexanol,
      2-methylene-5-(1-methylethenyl) which were reported to have specifically
      antimicrobial activity.

PMID- 25389518
TI  - Crystal structure of peptidyl-tRNA hydrolase from a Gram-positive bacterium,
      Streptococcus pyogenes at 2.19 A resolution shows the closed structure of the
      substrate-binding cleft.
AB  - Peptidyl-tRNA hydrolase (Pth) catalyses the release of tRNA and peptide
      components from peptidyl-tRNA molecules. Pth from a Gram-positive bacterium
      Streptococcus pyogenes (SpPth) was cloned, expressed, purified and crystallised.
      Three-dimensional structure of SpPth was determined by X-ray crystallography at
      2.19 A resolution. Structure determination showed that the asymmetric unit of the
      unit cell contained two crystallographically independent molecules, designated A
      and B. The superimposition of C(alpha) traces of molecules A and B showed an
      r.m.s. shift of 0.4 A, indicating that the structures of two crystallographically
      independent molecules were identical. The polypeptide chain of SpPth adopted an
      overall alpha/beta conformation. The substrate-binding cleft in SpPth is formed
      with three loops: the gate loop, Ile91-Leu102; the base loop, Gly108-Gly115; and
      the lid loop, Gly136-Gly150. Unlike in the structures of Pth from Gram-negative
      bacteria, the entry to the cleft in the structure of SpPth appeared to be
      virtually closed. However, the conformations of the active site residues were
      found to be similar. 

PMID- 25389519
TI  - Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a
      clinical setting.
AB  - Diagnostic accuracy in FDG-PET imaging highly depends on the operating
      procedures. In this clinical study on dementia, we compared the diagnostic
      accuracy at a single-subject level of a) Clinical Scenarios, b) Standard FDG
      Images and c) Statistical Parametrical (SPM) Maps generated via a new optimized
      SPM procedure. We evaluated the added value of FDG-PET, either Standard FDG
      Images or SPM Maps, to Clinical Scenarios. In 88 patients with neurodegenerative
      diseases (Alzheimer's Disease-AD, Frontotemporal Lobar Degeneration-FTLD,
      Dementia with Lewy bodies-DLB and Mild Cognitive Impairment-MCI), 9 neuroimaging
      experts made a forced diagnostic decision on the basis of the evaluation of the
      three types of information. There was also the possibility of a decision of
      normality on the FDG-PET images. The clinical diagnosis confirmed at a long-term
      follow-up was used as the gold standard. SPM Maps showed higher sensitivity and
      specificity (96% and 84%), and better diagnostic positive (6.8) and negative
      (0.05) likelihood ratios compared to Clinical Scenarios and Standard FDG Images.
      SPM Maps increased diagnostic accuracy for differential diagnosis (AD vs. FTD;
      beta 1.414, p = 0.019). The AUC of the ROC curve was 0.67 for SPM Maps, 0.57 for
      Clinical Scenarios and 0.50 for Standard FDG Images. In the MCI group, SPM Maps
      showed the highest predictive prognostic value (mean LOC = 2.46), by identifying
      either normal brain metabolism (exclusionary role) or hypometabolic patterns
      typical of different neurodegenerative conditions.

PMID- 25389520
TI  - Altered functional connectivity links in neuroleptic-naive and neuroleptic
      treated patients with schizophrenia, and their relation to symptoms including
      volition.
AB  - In order to analyze functional connectivity in untreated and treated patients
      with schizophrenia, resting-state fMRI data were obtained for whole-brain
      functional connectivity analysis from 22 first-episode neuroleptic-naive
      schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS)
      patients, and 60 healthy controls (HC). Reductions were found in untreated and
      treated patients in the functional connectivity between the posterior cingulate
      gyrus and precuneus, and this was correlated with the reduction in volition from
      the Positive and Negative Symptoms Scale (PANSS), that is in the willful
      initiation, sustenance, and control of thoughts, behavior, movements, and speech,
      and with the general and negative symptoms. In addition in both patient groups
      interhemispheric functional connectivity was weaker between the orbitofrontal
      cortex, amygdala and temporal pole. These functional connectivity changes and the
      related symptoms were not treated by the neuroleptics. Differences between the
      patient groups were that there were more strong functional connectivity links in
      the NNS patients (including in hippocampal, frontal, and striatal circuits) than
      in the NTS patients. These findings with a whole brain analysis in untreated and
      treated patients with schizophrenia provide evidence on some of the brain regions
      implicated in the volitional, other general, and negative symptoms, of
      schizophrenia that are not treated by neuroleptics so have implications for the
      development of other treatments; and provide evidence on some brain systems in
      which neuroleptics do alter the functional connectivity.

PMID- 25389521
TI  - Quality of Life and Toxicity after SBRT for Organ-Confined Prostate Cancer, a 7
      Year Study.
AB  - OBJECTIVES: Stereotactic body radiation therapy (SBRT) yields excellent disease
      control for low- and intermediate-risk prostate cancer by delivering high doses
      of radiation in a small number of fractions. Our report presents a 7-year update
      on treatment toxicity and quality of life (QOL) from 515 patients treated with
      prostate SBRT. METHODS: From 2006 to 2009, 515 patients with clinically
      localized, low-, intermediate-, and high-risk prostate cancer were treated with
      SBRT using Cyberknife technology. Treatment consisted of 35-36.25 Gy in 5
      fractions. Seventy-two patients received hormone therapy. Toxicity was assessed
      at each follow-up visit using the expanded prostate cancer index composite (EPIC)
      questionnaire and the radiation therapy oncology group urinary and rectal
      toxicity scale. RESULTS: Median follow-up was 72 months. The actuarial 7-year
      freedom from biochemical failure was 95.8, 89.3, and 68.5% for low-, intermediate
      , and high-risk groups, respectively (p < 0.001). No patients experienced acute
      Grade 3 or 4 acute complications. Fewer than 5% of patients had any acute Grade 2
      urinary or rectal toxicity. Late toxicity was low, with Grade 2 rectal and
      urinary toxicity of 4 and 9.1%, respectively, and Grade 3 urinary toxicity of
      1.7%. Mean EPIC urinary and bowel QOL declined at 1 month post-treatment,
      returned to baseline by 2 years and remained stable thereafter. EPIC sexual QOL
      declined by 23% at 6-12 months and remained stable afterwards. Of patients potent
      at baseline evaluation, 67% remained potent at last follow-up. CONCLUSION: This
      study suggests that SBRT, when administered to doses of 35-36.25 Gy, is
      efficacious and safe. With long-term follow-up in our large patient cohort, we
      continue to find low rates of late toxicity and excellent rates of biochemical
      control.

PMID- 25389524
TI  - Teleradiology usage and user satisfaction with the telemedicine system operated
      by medecins sans frontieres.
AB  - Medecins Sans Frontieres (MSF) began a pilot trial of store-and-forward
      telemedicine in 2010, initially operating separate networks in English, French,
      and Spanish; these were merged into a single, multilingual platform in 2013. We
      reviewed the pattern of teleradiology usage on the MSF telemedicine platform in
      the 4-year period from April 2010. In total, 564 teleradiology cases were
      submitted from 22 different countries. A total of 1114 files were uploaded with
      the 564 cases, the majority being of type JPEG (n = 1081, 97%). The median file
      size was 938 kb (interquartile range, IQR 163-1659). A panel of 14 radiologists
      was available to report cases, but most (90%) were reported by only 4
      radiologists. The median radiologist response time was 6.1 h (IQR 3.0-20). A user
      satisfaction survey was sent to 29 users in the last 6 months of the study. There
      was a 28% response rate. Most respondents found the radiologist's advice helpful
      and all of them stated that the advice assisted in clarification of a diagnosis.
      Although some MSF sites made substantial use of the system for teleradiology,
      there is considerable potential for expansion. More promotion of telemedicine may
      be needed at different levels of the organization to increase engagement of
      staff. 

PMID- 25389523
TI  - An evolving perspective on the Pseudomonas aeruginosa orphan quorum sensing
      regulator QscR.
AB  - Many Proteobacteria govern responses to changes in cell density by using acyl
      homoserine lactone (AHL) quorum-sensing (QS) signaling. Similar to the LuxI-LuxR
      system described in Vibrio fischeri, a minimal AHL QS circuit comprises a pair of
      genes, a luxI-type synthase gene encoding an enzyme that synthesizes an AHL and a
      luxR-type AHL-responsive transcription regulator gene. In most bacteria that
      utilize AHL QS, cognate luxI and luxR homologs are found in proximity to each
      other on the chromosome. However, a number of recent reports have identified luxR
      homologs that are not linked to luxI homologs; in some cases luxR homologs have
      been identified in bacteria that have no luxI homologs. A luxR homolog without a
      linked luxI homologs is termed an orphan or solo. One of the first reports of an
      orphan was on QscR in Pseudomonas aeruginosa. The qscR gene was revealed by whole
      genome sequencing and has been studied in some detail. P. aeruginosa encodes two
      AHL synthases and three AHL responsive receptors, LasI-LasR form a cognate
      synthase-receptor pair as do RhlI-RhlR. QscR lacks a linked synthase and responds
      to the LasI-generated AHL. QS regulation of gene expression in P. aeruginosa
      employs multiple signals and occurs in the context of other interconnected
      regulatory circuits that control diverse physiological functions. QscR affects
      virulence of P. aeruginosa, and although it shows sensitivity to the LasI
      generated AHL, 3-oxo-dodecanoylhomoserine lactone, it's specificity is relaxed
      compared to LasR and can respond equally well to several AHLs. QscR controls a
      set of genes that overlaps the set regulated by LasR. QscR is comparatively easy
      to purify and study in vitro, and has become a model for understanding the
      biochemistry of LuxR homologs. In fact there is a crystal structure of QscR bound
      to the LasI-generated AHL. Here, we review the current state of research
      concerning QscR and highlight recent advances in our understanding of its
      structure and biochemistry. 

PMID- 25389522
TI  - Sibling rivalry: related bacterial small RNAs and their redundant and non
      redundant roles.
AB  - Small RNA molecules (sRNAs) are now recognized as key regulators controlling
      bacterial gene expression, as sRNAs provide a quick and efficient means of
      positively or negatively altering the expression of specific genes. To date,
      numerous sRNAs have been identified and characterized in a myriad of bacterial
      species, but more recently, a theme in bacterial sRNAs has emerged: the presence
      of more than one highly related sRNAs produced by a given bacterium, here termed
      sibling sRNAs. Sibling sRNAs are those that are highly similar at the nucleotide
      level, and while it might be expected that sibling sRNAs exert identical
      regulatory functions on the expression of target genes based on their high degree
      of relatedness, emerging evidence is demonstrating that this is not always the
      case. Indeed, there are several examples of bacterial sibling sRNAs with non
      redundant regulatory functions, but there are also instances of apparent
      regulatory redundancy between sibling sRNAs. This review provides a comprehensive
      overview of the current knowledge of bacterial sibling sRNAs, and also discusses
      important questions about the significance and evolutionary implications of this
      emerging class of regulators. 

PMID- 25389525
TI  - Assessing the Quality of Teleconsultations in a Store-And-Forward Telemedicine
      Network - Long-Term Monitoring Taking into Account Differences between Cases.
AB  - We have previously proposed a method for assessing the quality of individual
      teleconsultation cases; this paper proposes an additional step to allow the long
      term monitoring of quality. The basic scenario is a teleconsultation system (aka
      an e-referral system or a tele-expertise system) where the referrer posts a
      question about a clinical case, the question is relayed to an appropriate expert,
      and the chosen expert provides an answer. The people running this system want
      assurances that it is stable, i.e., they want routine quality assurance
      information about the "output" from the "process." This requires two things. It
      needs a method of assessing the quality of individual patient consultations. And
      it needs a method for taking into account differences between patients, so that
      these quality assessments can be compared longitudinally. Building on the
      previously proposed methodology, the present paper proposes two techniques for
      measuring the difficulty posed by a particular teleconsultation. The first is an
      indirect method, similar to a willingness to pay economic estimation. The second
      is a direct method. Using these two methods with real data from a telemedicine
      network showed that the first method was feasible, but did not produce useful
      results in a pilot trial. The second method, while more laborious, was also
      feasible and did produce useful results. Thus, when output quality is measured,
      an allowance can be made for the characteristics of the case submitted. This
      means that fluctuations in output quality can be attributed to variations in the
      process (network) or to variations in the raw materials (queries submitted to the
      network). Long-term quality assurance should assist those providing telemedicine
      services in low-resource settings to ensure that the services are operated
      effectively and efficiently, despite the constraints and complexities of the
      environment. 

PMID- 25389526
TI  - New transposon tools tailored for metabolic engineering of gram-negative
      microbial cell factories.
AB  - Re-programming microorganisms to modify their existing functions and/or to bestow
      bacteria with entirely new-to-Nature tasks have largely relied so far on
      specialized molecular biology tools. Such endeavors are not only relevant in the
      burgeoning metabolic engineering arena but also instrumental to explore the
      functioning of complex regulatory networks from a fundamental point of view. A la
      carte modification of bacterial genomes thus calls for novel tools to make
      genetic manipulations easier. We propose the use of a series of new broad-host
      range mini-Tn5-vectors, termed pBAMDs, for the delivery of gene(s) into the
      chromosome of Gram-negative bacteria and for generating saturated mutagenesis
      libraries in gene function studies. These delivery vectors endow the user with
      the possibility of easy cloning and subsequent insertion of functional cargoes
      with three different antibiotic-resistance markers (kanamycin, streptomycin, and
      gentamicin). After validating the pBAMD vectors in the environmental bacterium
      Pseudomonas putida KT2440, their use was also illustrated by inserting the entire
      poly(3-hydroxybutyrate) (PHB) synthesis pathway from Cupriavidus necator in the
      chromosome of a phosphotransacetylase mutant of Escherichia coli. PHB is a
      completely biodegradable polyester with a number of industrial applications that
      make it attractive as a potential replacement of oil-based plastics. The non
      selective nature of chromosomal insertions of the biosynthetic genes was
      evidenced by a large landscape of PHB synthesis levels in independent clones. One
      clone was selected and further characterized as a microbial cell factory for PHB
      accumulation, and it achieved polymer accumulation levels comparable to those of
      a plasmid-bearing recombinant. Taken together, our results demonstrate that the
      new mini-Tn5-vectors can be used to confer interesting phenotypes in Gram
      negative bacteria that would be very difficult to engineer through direct
      manipulation of the structural genes. 

PMID- 25389527
TI  - Identification and characterization of microsatellites in expressed sequence tags
      and their cross transferability in different plants.
AB  - Expressed sequence tags (EST) are potential source for the development of genic
      microsatellite markers, gene discovery, comparative genomics, and other genomic
      studies. In the present study, 7630 ESTs were examined from NCBI for SSR
      identification and characterization. A total of 263 SSRs were identified with an
      average density of one SSR/4.2 kb (3.4% frequency). Analysis revealed that
      trinucleotide repeats (47.52%) were most abundant followed by tetranucleotide
      (19.77%), dinucleotide (19.01%), pentanucleotide (9.12%), and hexanucleotide
      repeats (4.56%). Functional annotation was done through homology search and gene
      ontology, and 35 EST-SSRs were selected. Primer pairs were designed for
      evaluation of cross transferability and polymorphism among 11 plants belonging to
      five different families. Total 402 alleles were generated at 155 loci with an
      average of 2.6 alleles/locus and the polymorphic information content (PIC) ranged
      from 0.15 to 0.92 with an average of 0.75. The cross transferability ranged from
      34.84% to 98.06% in different plants, with an average of 67.86%. Thus, the
      validation study of annotated 35 EST-SSR markers which correspond to particular
      metabolic activity revealed polymorphism and evolutionary nature in different
      families of Angiospermic plants. 

PMID- 25389528
TI  - Speckle-tracking and tissue-Doppler stress echocardiography in arterial
      hypertension: a sensitive tool for detection of subclinical LV impairment.
AB  - Early diagnosis of cardiac alterations in hypertensive heart disease is still
      challenging. Since such patients might have depressed global LV systolic strain
      or strain rate when EF is still normal, speckle-tracking echocardiography (STE)
      and tissue-Doppler imaging (TDI) combined with stress echocardiography might
      improve early diagnosis of cardiac alterations. In this prospective study
      standard 2D Doppler echocardiography, STE, and TDI were performed at rest and
      during bicycle exercise in 92 consecutive patients--46 hypertensive subjects with
      normal ejection fraction and 46 healthy controls. STE and TDI were used to
      measure global peak systolic LV circumferential strain (CS), longitudinal strain
      (LS), and longitudinal strain rate (SR). Mean arterial blood pressure was
      significantly higher in hypertensive patients at rest (100.8 mmHg SD 13.5 mmHg;
      P=0.002) and during physical exercise testing (124.2 mmHg SD 13.4 mmHg; P=0.003).
      Hypertensive patients had significantly reduced values of systolic CS (P=0.001),
      LS (P=0.014), and SR (P<0.001) at rest as well as during physical exercise-CS
      (P<0.001), LS (P<0.001), and SR (P<0.001). Using STE and TDI, reduced LV systolic
      strain and strain rate consistent with early cardiac alterations can be detected
      in patients with arterial hypertension. These findings were evident at rest and
      markedly pronounced during exercise echocardiography.

PMID- 25389529
TI  - Advanced tracers in PET imaging of cardiovascular disease.
AB  - Cardiovascular disease is the leading cause of death worldwide. Molecular imaging
      with targeted tracers by positron emission tomography (PET) allows for the
      noninvasive detection and characterization of biological changes at the molecular
      level, leading to earlier disease detection, objective monitoring of therapies,
      and better prognostication of cardiovascular diseases progression. Here we
      review, the current role of PET in cardiovascular disease, with emphasize on
      tracers developed for PET imaging of cardiovascular diseases. 

PMID- 25389530
TI  - Blocking alphaVbeta3 integrin ligand occupancy inhibits the progression of
      albuminuria in diabetic rats.
AB  - This study determined if blocking ligand occupancy of the alphaVbeta3 integrin
      could inhibit the pathophysiologic changes that occur in the early stages of
      diabetic nephropathy (DN). Diabetic rats were treated with either vehicle or a
      monoclonal antibody that binds the beta3 subunit of the alphaVbeta3 integrin.
      After 4 weeks of diabetes the urinary albumin to creatinine ratio (UACR)
      increased in both diabetic animals that subsequently received vehicle and in the
      animals that subsequently received the anti-beta3 antibody compared with control
      nondiabetic rats. After 8 weeks of treatment the UACR continued to rise in the
      vehicle-treated rats; however it returned to levels comparable to control
      nondiabetic rats in rats treated with the anti-beta3 antibody. Treatment with the
      antibody prevented the increase of several profibrotic proteins that have been
      implicated in the development of DN. Diabetes was associated with an increase in
      phosphorylation of the beta3 subunit in kidney homogenates from diabetic animals,
      but this was prevented by the antibody treatment. This study demonstrates that,
      when administered after establishment of early pathophysiologic changes in renal
      function, the anti-beta3 antibody reversed the effects of diabetes normalizing
      albuminuria and profibrotic proteins in the kidney to the levels observed in
      nondiabetic control animals. 

PMID- 25389531
TI  - Nonhuman primate models of type 1 diabetes mellitus for islet transplantation.
AB  - Islet transplantation is an attractive treatment of type 1 diabetes mellitus
      (T1DM). Animal models of diabetes mellitus (DM) contribute a lot to the
      experimental studies of islet transplantation and to evaluations of isolated
      islet grafts for future clinical applications. Diabetic nonhuman primates (NHPs)
      represent the suitable models of DMs to better evaluate the effectiveness of
      islet transplantation, to assess new strategies for controlling blood glucose
      (BG), relieving immune rejection, or prolonging islet survival, and eventually to
      translate the preclinical data into tangible clinical practice. This review
      introduces some NHP models of DM, clarifies why and how the models should be
      used, and elucidates the usefulness and limitations of the models in islet
      transplantation. 

PMID- 25389532
TI  - Immune dysfunction in Rett syndrome patients revealed by high levels of serum
      anti-N(Glc) IgM antibody fraction.
AB  - Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%)
      female infants, is associated with loss-of-function mutations in the gene
      encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent
      kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we
      aimed to evaluate the function of the immune system by measuring serum
      immunoglobulins (IgG and IgM) in RTT patients (n = 53) and, by comparison, in age
      matched children affected by non-RTT pervasive developmental disorders (non-RTT
      PDD) (n = 82) and healthy age-matched controls (n = 29). To determine
      immunoglobulins we used both a conventional agglutination assay and a novel ELISA
      based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a
      synthetic N-glucosylated peptide. Both assays provided evidence for an increase
      in IgM titer, but not in IgG, in RTT patients relative to both healthy controls
      and non-RTT PDD patients. The significant difference in IgM titers between RTT
      patients and healthy subjects in the CSF114(Glc) assay (P = 0.001) suggests that
      this procedure specifically detects a fraction of IgM antibodies likely to be
      relevant for the RTT disease. These findings offer a new insight into the
      mechanism underlying the Rett disease as they unveil the possible involvement of
      the immune system in this pathology. 

PMID- 25389533
TI  - The influence of monoamine oxidase variants on the risk of betel quid-associated
      oral and pharyngeal cancer.
AB  - Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human
      carcinogens illustrated by International Agency for Research on Cancer and are
      closely associated with an elevated risk of oral potentially malignant disorders
      (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN,
      arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing
      reactive oxygen species (ROS). The aim of this study was to investigate whether
      the variants of the susceptible candidate MAO genes are associated with OPMDs and
      oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was
      found in in vitro studies. Using paired human tissues, we confirmed the
      significantly decreased expression of MAO-A and MAO-B in cancerous tissues when
      compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A
      single nucleotide polymorphism variants are significantly linked with oral and
      pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G
      allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion,
      we suggested that susceptible MAO family variants associated with oral and
      pharyngeal cancer may be implicated in the modulation of MAO gene activity
      associated with ROS. 

PMID- 25389534
TI  - Characterisation of Drosophila Ubx CPTI000601 and hth CPTI000378 protein trap
      lines.
AB  - In Drosophila, protein trap strategies provide powerful approaches for the
      generation of tagged proteins expressed under endogenous control. Here, we
      describe expression and functional analysis to evaluate new Ubx and hth protein
      trap lines generated by the Cambridge Protein Trap project. Both protein traps
      exhibit spatial and temporal expression patterns consistent with the reported
      endogenous pattern in the embryo. In imaginal discs, Ubx-YFP is expressed
      throughout the haltere and 3rd leg imaginal discs, while Hth-YFP is expressed in
      the proximal regions of haltere and wing discs but not in the pouch region. The
      Ubx (CPTI000601) line is semilethal as a homozygote. No T3/A1 to T2
      transformations were observed in the embryonic cuticle or the developing midgut.
      The homozygous survivors, however, exhibit a weak haltere phenotype with a few
      wing-like marginal bristles on the haltere capitellum. Although hth (CPTI000378)
      is completely lethal as a homozygote, the hth (CPTI000378) /hth (C1) genotype is
      viable. Using a hth deletion (Df(3R)BSC479) we show that hth (CPTI000378)
      /Df(3R)BSC479 adults are phenotypically normal. No transformations were observed
      in hth (CPTI000378), hth (CPTI000378) /hth (C1), or hth (CPTI000378)
      /Df(3R)BSC479 embryonic cuticles. We have successfully characterised the Ubx-YFP
      and Hth-YFP protein trap lines demonstrating that the tagged proteins show
      appropriate expression patterns and produce at least partially functional
      proteins.

PMID- 25389535
TI  - A premature termination of human epidermal growth factor receptor transcription
      in Escherichia coli.
AB  - Our success in producing an active epidermal growth factor receptor (EGFR)
      tyrosine kinase in Escherichia coli encouraged us to express the full-length
      receptor in the same host. Despite its large size, we were successful at
      producing the full-length EGFR protein fused to glutathione S-transferase (GST)
      that was detected by Western blot analysis. Moreover, we obtained a majoritarian
      truncated GST-EGFR form detectable by gel electrophoresis and Western blot. This
      truncated protein was purified and confirmed by MALDI-TOF/TOF analysis to belong
      to the N-terminal extracellular region of the EGFR fused to GST. Northern blot
      analysis showed two transcripts suggesting the occurrence of a transcriptional
      arrest. 

PMID- 25389536
TI  - Prevalence and imaging characteristics of palatine tonsilloliths detected by CT
      in 2,873 consecutive patients.
AB  - AIM: Tonsilloliths are calcified structures that develop in tonsillar crypts.
      They are commonly detected in daily clinical practice. The prevalence of
      tonsilloliths was 16 to 24% in previous reports, but it is inconsistent with
      clinical experience. The aim of this study is to clarify the prevalence, number,
      and size distribution of tonsilloliths using computed tomography (CT) in a
      relatively large number of patients. MATERIALS AND METHODS: We retrospectively
      reviewed the scans of 2,873 patients referred for CT examinations with regard to
      tonsilloliths. RESULTS: Palatine tonsilloliths were found in 1,145 out of 2,873
      patients (39.9%). The prevalence of tonsilloliths increased with age, and most
      commonly in patients of ages 50-69. The prevalence in the 30s and younger was
      statistically lower than in the 40s and older (P < 0.05). The number of
      tonsilloliths per palatine tonsil ranged from one to 18. The size of the
      tonsilloliths ranged from 1 to 10 mm. For the patients with multiple CT
      examinations,the number of tonsilloliths increased in 51 (3.9%) and decreased in
      84 (6.5%) of the tonsils. CONCLUSIONS: As palatine tonsilloliths are common
      conditions, screenings for tonsilloliths during the diagnosis of soft tissue
      calcifications should be included in routine diagnostic imaging.

PMID- 25389537
TI  - [Behavioral approach and inhibition systems and substance use in adolescence].
AB  - One of the-characteristic features of adolescence 'is a tendency to risky
      behaviors including experimentation with psychoactive substances. The current
      review covered empirical studies on the associations of Behavioral Approach
      System (BAS) and Behavioral Inhibition System (BIS) with adolescent substance
      use. The best predictors are the two components of BAS- reward responsiveness and
      fun seeking/impulsivity; the evidence on the role of BIS is contradictory. Recent
      neurological studies suggest that developmental differences in brain pathways
      underlying approach and avoidance motivation may be one mechanism through which
      adolescents are placed at greater risk for substance experimentation and misuse.
      Although adolescents as a group are considered risk-takers, some adolescents will
      be more prone than others to engage in risky.behaviors, putting them at
      potentially greater risk for negative outcomes. These individual and
      developmental differences may help explain vulnerability in some individuals to
      risk-taking associated with substance use. Efforts to prevent or minimize
      adolescent risk-taking should focus on changing the context in which risky
      activity takes place.

PMID- 25389538
TI  - [Clinical potential and possibilities of using buspirone in the treatment of
      anxiety disorders].
AB  - The article reviews current publications on the epidemiology, psychopathology,
      diagnostic criteria and comorbidity of most frequently encountered in the
      practice anxiety disorders: generalized anxiety disorder and panic disorder.
      Special attention is paid to the pharmacotherapy of anxiety disorders in the
      aspect of efficacy of main classes of drugs, including buspirone. The results of
      clinical trials of buspirone are presented.

PMID- 25389539
TI  - [Pathophysiological aspects of the use of botulinum toxin dysport in the upper
      motor neuron lesion].
AB  - The most frequent causes of disability of patients with neurological diseases are
      motor disorders in the upper motor neuron lesion caused by the damage of the
      brain and/or the spinal cord that resulted in the formation of spastic paresis
      and paralysis. The correct understanding of the pathophysiological basis of
      clinical presentations of the upper motor neuron lesion will allow to chose the
      most adequate and prognostically successful methods of treatment. Currently,
      treatment with botulotoxin can be considered as such a method. This method in the
      combination with non-pharmacological rehabilitation decreases the activity of
      phasic and tonic stretching reflexes, associated contractions, synkinesia,
      spastic dystonia and spasticity that leads to the increase in muscle elasticity,
      mobility of extremities, reduction of pain, joint stiffness and soft tissue
      deformation that, in its turn, can increase the independence of the patient from
      any help.

PMID- 25389540
TI  - [Dementia and small vessel diseases of the brain].
AB  - Clinical and pathogenetic characteristics of dementia caused by small vessel
      lesions are presented. It is emphasized that this variant of vascular dementia is
      the most frequent in clinical practice. Clinical examination, accurate assessment
      of the disease history and using of modern neuroimaging techniques are important
      for the diagnosis. The drugs that impact on risk factors, including
      disaggregants, and metabolic drugs (nicergoline) are widely used in the treatment
      of dementia. These drugs are highly effective and safe.

PMID- 25389541
TI  - WITHDRAWN: Retraction notice to: "Acute ethanol administration affects memory
      reactivation: a look at the neuronal density and apoptosis in the rat
      hippocampus" [Pharmacology, Biochemistry and Behavior 102/2 (2012) 321-328 of
      retracted article].

PMID- 25389542
TI  - Secondary jaw aneurysmal bone cyst (JABC)--a possible misnomer? A review of
      literature on secondary JABCs, their pathogenesis and oncogenesis.
AB  - CONTEXT: Aneurysmal bone cysts are rare pseudocysts, commonly seen in long bones
      and vertebral column. Although a well described and reported lesion, many
      misconceptions still prevail regarding their etiopathogenesis. Many of the
      reported cases of jaw aneurysmal bone cysts (JABC) present with another bone
      pathology. AIMS: The purpose of this review was to evaluate the incidence of
      neoplastic lesions occurring simultaneously with a JABC (in contrast to primary
      JABCs). Any pathogenetic and oncogenetic association between primary and
      secondary jaw ABCs has been reviewed and discussed. SETTINGS AND DESIGN: A
      methodical narrative review of literature was performed, given the incidence of
      mostly case reports on this topic. METHODS AND MATERIAL: A methodical electronic
      search of Pubmed, Pubmed Central, Medline and Cochrane databases was performed
      for reported cases of JABC. These articles were analysed and segregated into
      primary and secondary ABC and, if secondary, the lesion it concurrently occurred
      with. Another search was conducted to yield articles discussing the
      cytopathogenetic and oncogenetic origins of ABCs. RESULTS AND CONCLUSIONS: About
      15% of the ABCs reported were of secondary nature. Amongst the associated
      lesions, cement-ossifying fibroma and ossifying fibroma were the most common,
      followed by fibrous dysplasia and central giant cell granuloma. No ABCs were
      associated with metastatic changes. The search for histopathogenesis pointed to a
      specific cytogenetic abnormality as the origin of primary ABCs, with USP6 as its
      main oncogene and spindle cell as the neoplastic cell, unlike with secondary
      ABCs, suggesting that they are distinct pathological processes.

PMID- 25389543
TI  - Do nurses feel stressed? A perspective from primary  health care.
AB  - This study describes nurses' experiences of stress in primary healthcare
      settings, and examines correlations between stress and personal factors. There
      were 187 nurses from 18 public primary care centers participating, drawn from one
      county of Lithuania. The Expanded Nursing Stress Scale was used to evaluate the
      study data. The study indicates that in primary healthcare centers, nurses
      working with adult patients experienced less stress than those working with
      younger patients. The most frequently reported stressors were those related to
      death and dying, and conflicts with physicians and patients and their families.
      In particular, older nurses more frequently experienced stress related to death
      and dying. The intensity of nurses' stress in conflict situations with physicians
      was related to age, however, the depth of work experience in the healthcare
      setting was more influential. Findings indicate that more detailed research is
      needed regarding stress experiences in primary health care, and especially the
      related impact of the social contexts involved in the setting.

PMID- 25389544
TI  - Retraction: Chan, M.-f.,Wong, F. K.Y., Chang, K., Chow, S.,   Chung, L., Lee,W.
      m. and Lee, R. (2009), Identifying   patient readmission subtypes from unplanned
      readmissions   to hospitals in Hong Kong:A cluster analysis. Nursing &   Health
      Sciences. 11: 37-44.

PMID- 25389545
TI  - Traffic Safety Facts, 2010 Data: Young Drivers.

PMID- 25389546
TI  - In memory of an exceptional cardiologist and collegague: Magda Heras i Fortuny
      (1953-2014).

PMID- 25389547
TI  - Magda Heras i Fortuny, an indelible imprint on Revista Espanola de Cardiologia.

PMID- 25389548
TI  - The vaginal microbiota and susceptibility to HIV.
AB  - There is some evidence that the risk of HIV infection per heterosexual act is
      higher in low-income countries than in high-income countries. We hypothesize that
      variations in per sex-act transmission probability of HIV may in part be
      attributed to differences in the composition and function of the vaginal
      microbiota between different populations. This paper presents data that are in
      support of this hypothesis. Experimental and clinical studies have provided
      evidence that the normal vaginal microbiota plays a protective role against
      acquisition of HIV and other sexually transmitted infections. Epidemiological
      studies have convincingly shown that disturbances of the vaginal microbiome,
      namely intermediate flora and bacterial vaginosis, increase the risk of
      acquisition of HIV infection. A review of the literature found large differences
      in prevalence of bacterial vaginosis between different populations, with the
      highest prevalence rates found in black populations. Possible explanations for
      these differences are presented including data suggesting that there are ethnic
      differences in the composition of the normal vaginal microbiota. Lastly,
      interventions are discussed to restore and maintain a healthy vaginal
      environment.

PMID- 25389549
TI  - The management of urinary incontinence in the   male neurological patient.
AB  - PURPOSE OF REVIEW: Urinary incontinence in male neurological patients is a very
      frequent problem but treatment remains challenging. Thus, we summarize and
      highlight the latest developments in the management of urinary incontinence in
      this specific patient population. RECENT FINDINGS: Intermittent self
      catheterization, antimuscarinics, intradetrusor injections with
      onabotulinumtoxinA, augmentation cystoplasty, urinary diversion, and artificial
      urinary sphincter are the cornerstones of the armamentarium for treating
      neurogenic urinary incontinence. However, with the exception of
      onabotulinumtoxinA intradetrusor injections, level of evidence is often low and
      male-specific outcomes are virtually not available. Alternative conservative
      and/or minimally invasive procedures such as neuromodulation techniques and
      suburethral suspension devices provide promising data with apparently good safety
      and tolerability but still insufficient evidence lacking randomized control
      trials. SUMMARY: Standard options for treatment of urinary incontinence in
      neurological patients remain largely unchanged. Alternative treatment options,
      especially of conservative or minimally invasive character, have the potential to
      further broaden the therapeutic spectrum. While a higher level of evidence is
      needed to assess the potential of such therapeutic approaches, randomized
      controlled trials in the male neurological population present a challenge. To
      truly advance treatment of urinary continence in male neurological patients, well
      designed, multicenter studies are warranted.

PMID- 25389550
TI  - Urologists fix the plumbing, but can they reinforce   the walls?

PMID- 25389552
TI  - Bone health and chronic kidney disease: another   reason for partial nephrectomy?
AB  - PURPOSE OF REVIEW: To review the potential role of surgically induced nephron
      loss in calcium metabolism and its consequences on bone heath, and possible
      impact of surgical management of renal tumors on bone disorders. RECENT FINDINGS:
      With long-term oncological equivalence to radical nephrectomy and renal
      functional benefit, partial nephrectomy is the reference standard for management
      of clinical T1 renal tumors. Impact of nephron preservation on reduction of
      cardiovascular sequelae of chronic kidney disease is controversial. Reports from
      preclinical models provide a mechanism for surgically induced nephron loss
      leading to vitamin D and calcium metabolism dysregulation, resulting in
      osteoporosis. Emerging retrospective data also suggest that nephron preservation
      in setting of surgical treatment of renal malignancy may reduce risk of chronic
      kidney disease and sequelae, including osteoporosis and fractures. The magnitude
      and broader impact is unclear as other reports suggest that surgically induced
      chronic kidney disease is more stable than its medical counterpart. SUMMARY:
      Preclinical models and retrospective series suggest that surgically induced
      nephron loss is independently associated with development of osteopenia and
      fractures and biochemical events, which may lead to these subsequent events.
      Although prospective data is requisite, it is reasonable to prioritize nephron
      preservation when feasible in patients with preexisting disorders of bone
      metabolism, or to consider partial nephrectomy in patients with risk factors for
      osteoporosis.

PMID- 25389551
TI  - Long-term virological outcome in children on antiretroviral therapy in the UK and
      Ireland.
AB  - OBJECTIVE: To assess factors at the start of antiretroviral therapy (ART)
      associated with long-term virological response in children. DESIGN: Multicentre
      national cohort. METHODS: Factors associated with viral load below 400 copies/ml
      by 12 months and virologic failure among children starting 3/4-drug ART in the
      UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models.
      RESULTS: Nine hundred and ninety-seven children started ART at a median age of
      7.7 years (inter-quartile range 2.9-11.7), 251 (25%) below 3 years: 411 (41%)
      with efavirenz and two nucleoside reverse transcriptase inhibitors (EFVp2NRTIs),
      264 (26%) with nevirapine and two NRTIs (NVPp2NRTIs), 119 (12%; 106 NVP, 13 EFV)
      with non-nucleoside reverse transcriptase inhibitor and three NRTIs
      (NNRTIp3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens.
      Median follow-up after ART initiation was 5.7 (3.0-8.8) years. Viral load was
      less than 400 copies/ml by 12 months in 92% [95% confidence interval (CI) 91-94%]
      of the children. Time to suppression was similar across regimens (P1/40.10), but
      faster over calendar time, with older age and lower baseline viral load. Three
      hundred and thirtynine (34%) children experienced virological failure. Although
      progression to failure varied by regimen (P<0.001) and was fastest for NVPp2NRTIs
      regimens, risk after 2 years on therapy was similar for EFVp2NRTIs and
      NVPp2NRTIs, and lowest for NNRTIp3NRTIs regimens (P-interaction1/40.03). Older
      age, earlier calendar periods and maternal ART exposure were associated with
      increased failure risk. Early treatment discontinuation for toxicity occurred
      more frequently for NVP-based regimens, but 5-year cumulative incidence was
      similar: 6.1% (95% CI 3.9-8.9%) NVP, 8.3% (95% CI 5.6-11.6) EFV, and 9.8% (95% CI
      5.7-15.3%) protease inhibitor-based regimens (P1/40.48). CONCLUSION: Viral load
      suppression by 12 months was high with all regimens. NVPp3NRTIs regimens were
      particularly efficacious in the longer term and may be a good alternative to
      protease inhibitor-based ART in young children.

PMID- 25389553
TI  - Microstructural alterations of trabecular and cortical bone in long-term HIV
      infected elderly men on successful antiretroviral therapy.
AB  - OBJECTIVE: Progress in antiretroviral therapy (ART) has resulted in an almost
      normal life expectancy for HIV-infected individuals, but an increased risk of
      fragility fractures has been identified. We investigated the influence of long
      term HIV infection on successful ART on bone microstructure in elderly men.
      DESIGN: A cross-sectional, case-control study. METHODS: Dual-energy X-ray
      absorptiometry (DXA) and high-resolution peripheral quantitative computed
      tomography (HR-pQCT) were performed in 28 HIV-positive men between 60 and 70
      years old on successful ART. Controls were 112 HIV-negative men matched for age 4
      years and BMI (4 kg/ m2). RESULTS: HIV-positive men (median CD4p cell count, 589
      cells/ml; BMI, 24.8 kg/m2) had a median duration of HIV infection of 18.2 years.
      Compared with HIV-negative men, they had a lower DXA-measured areal bone mineral
      density at total hip (3.2%, P1/40.050) and ultra-distal radius (8.4%, P1/40.001).
      At distal radius and tibia, we observed microstructural alterations with a lower
      total density (16%, P1/4 0.005 and 14.3%, P1/4 0.039), trabecular density (11.6%,
      P1/4 0.012 and 12.2%, P1/4 0.007) and cortical area (17.5%, P1/4 0.002 and 12.2%,
      P1/4 0.01). In addition, they had a lower trabecular number (P1/4 0.036), higher
      trabecular spacing (P1/4 0.027) and lower cortical thickness (19.9%; P1/4 0.008)
      at distal radius. beta-crosslaps (CTX) and vitamin D levels were higher than in
      controls. By multivariate analyses, HIV status, higher CTX levels, lower physical
      activity and estradiol levels were determinants of bone density and
      microstructure alterations. CONCLUSION: HIV-infected elderly men on successful
      ART have trabecular and cortical bone microstructure alterations associated with
      higher bone resorption, despite adequate vitamin D supplementation.

PMID- 25389554
TI  - The confirmation of the DNA uptake  signal sequence needed for genetic 
      manipulation in Haemophilus parasuis.

PMID- 25389555
TI  - Author's response: Critique of paper on 'Effects of tetracycline and zinc on
      selection of methicillin-resistant Staphylococcus aureus (MRSA) sequence type 398
      in pigs'.

PMID- 25389556
TI  - Author's reply: To PMID 23955765.

PMID- 25389557
TI  - One-pot synthesis of multisubstituted 2-aminoquinolines from annulation of 1-aryl
      tetrazoles with internal alkynes via double C-H activation and denitrogenation.
AB  - An efficient, one-pot synthesis of multisubstituted 2-aminoquinolines from 1-aryl
      tetrazoles and internal alkynes has been developed. The reaction involves
      cyclization of 1-aryl tetrazoles with internal alkynes via rhodium(III)-catalyzed
      double C-H activation and copper(II)-mediated denitrogenation. 

PMID- 25389558
TI  - Characterization of a novel beta-glucosidase from Gongronella sp. W5 and its
      application in the hydrolysis of soybean isoflavone glycosides.
AB  - A novel beta-glucosidase named BglW5 from Gongronella sp. was isolated, purified,
      and characterized for the first time. Under solid state fermentation, the yield
      of BglW5 was 49.9 U/g fermented medium. BglW5 was stable over a wide pH range of
      3.0-8.5 and retained more than 50% of its maximal activity after incubation at 25
      degrees C for 96 h. The half-lives of BglW5 were 20 h at 60  degrees C, and 1 h
      at 70  degrees C. The activity of BglW5 was stimulated by xylose and fructose at
      concentrations up to 500 mM, with maximal stimulatory effect of 1.6-fold and 2.2
      fold, respectively. BglW5 converted isoflavone glycosides to aglycones, with a
      hydrolysis rate of 96.2% for daidzin and 96.7% for genistin. The productivities
      were 1.5 mmol L(-1) h(-1) for daidzein and 1.23 mmol L(-1) h(-1) for genistein,
      respectively. These features suggest that BglW5 has great application potential
      in the hydrolysis of soybean isoflavone glycosides. 

PMID- 25389559
TI  - Inhibitory effects of single-walled carbon nanotubes on biofilm formation from
      Bacillus anthracis spores.
AB  - This study reports the inhibitory effect of single walled carbon nanotubes
      (SWCNTs) on biofilm formation from Bacillus anthracis spores. Although the
      presence of 50 to 100 MUg ml(-1) of SWCNTs in the suspension increased spore
      attachment in the wells of 96-well plates, the presence of 200 MUg ml(-1) of
      SWCNTs in the germination solution decreased the germination percentage of the
      attached spores by 93.14%, completely inhibiting subsequent biofilm formation.
      The inhibition kinetics of 50 MUg ml(-1) SWCNTs on biofilm formation showed that
      this concentration inhibited biofilm formation by 81.2% after incubation for 48
      h. SWCNT treatment in the earlier stages of biofilm formation was more effective
      compared to treatment at later stages. Mature biofilms were highly resistant to
      SWCNT treatment. 

PMID- 25389560
TI  - Lead optimization and modulation of hERG activity in a series of aminooxazoline
      xanthene beta-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors.
AB  - The optimization of a series of aminooxazoline xanthene inhibitors of beta-site
      amyloid precursor protein cleaving enzyme 1 (BACE1) is described. An early lead
      compound showed robust Abeta lowering activity in a rat pharmacodynamic model,
      but advancement was precluded by a low therapeutic window to QTc prolongation in
      cardiovascular models consistent with in vitro activity on the hERG ion channel.
      While the introduction of polar groups was effective in reducing hERG binding
      affinity, this came at the expense of higher than desired Pgp-mediated efflux. A
      balance of low Pgp efflux and hERG activity was achieved by lowering the polar
      surface area of the P3 substituent while retaining polarity in the P2' side
      chain. The introduction of a fluorine in position 4 of the xanthene ring improved
      BACE1 potency (5-10-fold). The combination of these optimized fragments resulted
      in identification of compound 40, which showed robust Abeta reduction in a rat
      pharmacodynamic model (78% Abeta reduction in CSF at 10 mg/kg po) and also showed
      acceptable cardiovascular safety in vivo. 

PMID- 25389561
TI  - Impact of hemodialysis on the level of high-sensitivity cardiac troponins T in
      patients with end-stage renal disease.
AB  - AIM: The majority of patients with end-stage renal disease have chronically
      elevated concentrations of troponins, thus obscuring the diagnosis of myocardial
      infarction. We conducted a prospective study to examine the impact of
      hemodialysis on the level of high-sensitivity cardiac troponins T in asymptomatic
      patients with end-stage renal disease. METHODS: High-sensitivity cardiac
      troponins T were measured in 43 patients, before and after three dialysis
      sessions, over a one week period. RESULTS: Following dialysis, an average
      decrease of 7.6 pg/mL in high-sensitivity cardiac troponin T levels was observed
      which represents a 10.3% drop from baseline. Mutlivariable mixed linear
      regression models taking into account dialysis session (session 1, 2 or 3),
      sampling moment (before and after dialysis) and repeated measures on individuals
      revealed that the presence of coronary artery disease and elevated body mass
      index were associated with higher high-sensitivity cardiac troponin T levels when
      the other variables were held constant (CAD: beta [fixed effect estimate]=31.13
      pg/mL, P=0.022, 95%CI 4.46-57.80; body mass index: beta=2.57 kg/m2, P=0.008,
      95%CI 0.68-4.46). The significant fixed effect estimate for the interaction
      between gender and sampling moment indicated that the drop in high-sensitivity
      cardiac troponin T levels following dialysis was greater for women than for men
      (beta=5.75, P=0.049, 95% CI 0.02-11.47). When controlling for the variables
      mentioned above, this analysis confirmed that hemodialysis accounted for an 11.31
      pg/mL decrease in high-sensitivity cardiac troponin T levels (P<0.001, 95%CI 
      15.99 - -6.62) and that the values were higher in the first dialysis session than
      in the third (P=0.007; 95%CI 1.62-9.79). Ten patients (23%) were found to have no
      decrease or an increase in troponin levels after hemodialysis. CONCLUSION: In
      stable asymptomatic patients with end-stage renal disease, we have shown that
      hemodialysis reduces the blood concentration of high-sensitivity cardiac
      troponins T by at least 10%. Further studies are needed to confirm these results
      and determine their prognostic significance.

PMID- 25389563
TI  - The systematic assessment of traditional evidence from the premodern Chinese
      medical literature: a text-mining approach.
AB  - OBJECTIVES: This project aimed to develop an approach to evaluating information
      contained in the premodern Traditional Chinese Medicine (TCM) literature that was
      (1) comprehensive, systematic, and replicable and (2) able to produce
      quantifiable output that could be used to answer specific research questions in
      order to identify natural products for clinical and experimental research.
      METHODS: The project involved two stages. In stage 1, 14 TCM collections and
      compendia were evaluated for suitability as sources for searching; 8 of these
      were compared in detail. The results were published in the Journal of Alternative
      and Complementary Medicine. Stage 2 developed a text-mining approach for two of
      these sources. RESULTS: The text-mining approach was developed for Zhong Hua Yi
      Dian; Encyclopaedia of Traditional Chinese Medicine, 4th edition) and Zhong Yi
      Fang Ji Da Ci Dian; Great Compendium of Chinese Medical Formulae). This approach
      developed procedures for search term selection; methods for screening,
      classifying, and scoring data; procedures for systematic searching and data
      extraction; data checking procedures; and approaches for analyzing results.
      Examples are provided for studies of memory impairment and diabetic nephropathy,
      and issues relating to data interpretation are discussed. CONCLUSIONS: This
      approach to the analysis of large collections of the premodern TCM literature
      uses widely available sources and provides a text-mining approach that is
      systematic, replicable, and adaptable to the requirements of the particular
      project. Researchers can use these methods to explore changes in the names and
      conceptions of a disease over time, to identify which therapeutic methods have
      been more or less frequently used in different eras for particular disorders, and
      to assist in the selection of natural products for research efforts.

PMID- 25389562
TI  - Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary
      dysplasia.
AB  - RATIONALE: Pulmonary hypertension (PH) is associated with poor outcomes among
      preterm infants with bronchopulmonary dysplasia (BPD), but whether early signs of
      pulmonary vascular disease are associated with the subsequent development of BPD
      or PH at 36 weeks post-menstrual age (PMA) is unknown. OBJECTIVES: To
      prospectively evaluate the relationship of early echocardiogram signs of
      pulmonary vascular disease in preterm infants to the subsequent development of
      BPD and late PH (at 36 wk PMA). METHODS: Prospectively enrolled preterm infants
      with birthweights 500-1,250 g underwent echocardiogram evaluations at 7 days of
      age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were
      analyzed to identify early risk factors for BPD and late PH. MEASUREMENTS AND
      MAIN RESULTS: A total of 277 preterm infants completed echocardiogram and BPD
      assessments at 36 weeks PMA. The median gestational age at birth and birthweight
      of the infants were 27 weeks and 909 g, respectively. Early PH was identified in
      42% of infants, and 14% were diagnosed with late PH. Early PH was a risk factor
      for increased BPD severity (relative risk, 1.12; 95% confidence interval, 1.03
      1.23) and late PH (relative risk, 2.85; 95% confidence interval, 1.28-6.33).
      Infants with late PH had greater duration of oxygen therapy and increased
      mortality in the first year of life (P < 0.05). CONCLUSIONS: Early pulmonary
      vascular disease is associated with the development of BPD and with late PH in
      preterm infants. Echocardiograms at 7 days of age may be a useful tool to
      identify infants at high risk for BPD and PH.

PMID- 25389564
TI  - Transcallosal connectivity changes from infancy to late adulthood: an ex vivo
      diffusion spectrum imaging study of macaque brains.
AB  - Interhemispheric communication plays a critical role to ensure normal brain
      functions in cognition and behavior. Since non-human primate (NHP) brains
      resemble most aspects of the human brain, a thorough knowledge of
      interhemispheric cortical connectivity changes in NHP brains throughout the
      developmental and aging periods may provide valuable insights for translational
      and clinical research. In this study, formalin-fixed rhesus monkey brains aged
      from 1 to 24 years were utilized to examine transcallosal connectivity changes
      using diffusion spectrum imaging (DSI). It was found that the transcallosal
      connectivity for most frontal cortical areas, including dorso- and ventro-lateral
      prefrontal, premotor, and motor cortices, demonstrated pronounced age-related
      alterations. However, such a pattern was less obvious in temporal, posterior
      parietal, and visual cortices. The DSI results reveal the age-related evolution
      pattern of transcallosal connectivity in various cortical areas of macaque brains
      from infancy to late adulthood, and may have implications for assessing the
      functional defects or alterations in the associated cortical areas during brain
      development and aging in humans. 

PMID- 25389567
TI  - Vibrational spectroscopy and imaging.

PMID- 25389566
TI  - Noninvasive imaging of focal atherosclerotic lesions using fluorescence molecular
      tomography.
AB  - Insights into the etiology of stroke and myocardial infarction suggest that
      rupture of unstable atherosclerotic plaque is the precipitating event. Clinicians
      lack tools to detect lesion instability early enough to intervene, and are often
      left to manage patients empirically, or worse, after plaque rupture. Noninvasive
      imaging of the molecular events signaling prerupture plaque progression has the
      potential to reduce the morbidity and mortality associated with myocardial
      infarction and stroke by allowing early intervention. Here, we demonstrate proof
      of-principle in vivo molecular imaging of C-type natriuretic peptide receptor in
      focal atherosclerotic lesions in the femoral arteries of New Zealand white
      rabbits using a custom built fiber-based, fluorescence molecular tomography (FMT)
      system. Longitudinal imaging showed changes in the fluorescence signal intensity
      as the plaque progressed in the air-desiccated vessel compared to the uninjured
      vessel, which was validated by ex vivo tissue studies. In summary, we demonstrate
      the potential of FMT for noninvasive detection of molecular events leading to
      unstable lesions heralding plaque rupture.

PMID- 25389565
TI  - Tubulin bond energies and microtubule biomechanics determined from
      nanoindentation in silico.
AB  - Microtubules, the primary components of the chromosome segregation machinery, are
      stabilized by longitudinal and lateral noncovalent bonds between the tubulin
      subunits. However, the thermodynamics of these bonds and the microtubule
      physicochemical properties are poorly understood. Here, we explore the
      biomechanics of microtubule polymers using multiscale computational modeling and
      nanoindentations in silico of a contiguous microtubule fragment. A close match
      between the simulated and experimental force-deformation spectra enabled us to
      correlate the microtubule biomechanics with dynamic structural transitions at the
      nanoscale. Our mechanical testing revealed that the compressed MT behaves as a
      system of rigid elements interconnected through a network of lateral and
      longitudinal elastic bonds. The initial regime of continuous elastic deformation
      of the microtubule is followed by the transition regime, during which the
      microtubule lattice undergoes discrete structural changes, which include first
      the reversible dissociation of lateral bonds followed by irreversible
      dissociation of the longitudinal bonds. We have determined the free energies of
      dissociation of the lateral (6.9 +/- 0.4 kcal/mol) and longitudinal (14.9 +/- 1.5
      kcal/mol) tubulin-tubulin bonds. These values in conjunction with the large
      flexural rigidity of tubulin protofilaments obtained (18,000-26,000 pN.nm(2))
      support the idea that the disassembling microtubule is capable of generating a
      large mechanical force to move chromosomes during cell division. Our
      computational modeling offers a comprehensive quantitative platform to link
      molecular tubulin characteristics with the physiological behavior of
      microtubules. The developed in silico nanoindentation method provides a powerful
      tool for the exploration of biomechanical properties of other cytoskeletal and
      multiprotein assemblies. 

PMID- 25389568
TI  - Organ preservation in rectal adenocarcinoma (T1) T2-T3 Nx M0. Historical overview
      of the Lyon Sud - nice experience using contact x-ray brachytherapy and external
      beam radiotherapy for 120 patients.

PMID- 25389569
TI  - Editorial comment for Gozen et al.

PMID- 25389572
TI  - Reverse magnetic resonance signal from intraocular hemorrhage.
AB  - PURPOSE: To report the effect of massive intraocular hemorrhage on magnetic
      resonance imaging signal. METHODS: Case report. RESULTS: A 34-year-old power
      weightlifter developed sudden, nontraumatic loss of vision to no light perception
      in his right eye. Magnetic resonance imaging (MRI) revealed homogeneous bright
      signal on T1-weighted images and dark signal on T2-weighted images, opposite the
      signal of his normal left eye. These findings were suggestive of subacute massive
      intraocular hemorrhage. The patient elected enucleation for the blind, painful
      eye. The diagnosis made by MRI signal interpretation was confirmed by subsequent
      histopathology analysis. CONCLUSION: Based on hemoglobin degradation products,
      MRI can assist in judging the stage of blood breakdown and diagnosing intraocular
      pathology.

PMID- 25389571
TI  - Specific ion and buffer effects on protein-protein interactions of a monoclonal
      antibody.
AB  - Better predictive ability of salt and buffer effects on protein-protein
      interactions requires separating out contributions due to ionic screening,
      protein charge neutralization by ion binding, and salting-in(out) behavior. We
      have carried out a systematic study by measuring protein-protein interactions for
      a monoclonal antibody over an ionic strength range of 25 to 525 mM at 4 pH values
      (5, 6.5, 8, and 9) in solutions containing sodium chloride, calcium chloride,
      sodium sulfate, or sodium thiocyante. The salt ions are chosen so as to represent
      a range of affinities for protein charged and noncharged groups. The results are
      compared to effects of various buffers including acetate, citrate, phosphate,
      histidine, succinate, or tris. In low ionic strength solutions, anion binding
      affinity is reflected by the ability to reduce protein-protein repulsion, which
      follows the order thiocyanate > sulfate > chloride. The sulfate specific effect
      is screened at the same ionic strength required to screen the pH dependence of
      protein-protein interactions indicating sulfate binding only neutralizes protein
      charged groups. Thiocyanate specific effects occur over a larger ionic strength
      range reflecting adsorption to charged and noncharged regions of the protein. The
      latter leads to salting-in behavior and, at low pH, a nonmonotonic interaction
      profile with respect to sodium thiocyanate concentration. The effects of
      thiocyanate can not be rationalized in terms of only neutralizing double layer
      forces indicating the presence of an additional short-ranged protein-protein
      attraction at moderate ionic strength. Conversely, buffer specific effects can be
      explained through a charge neutralization mechanism, where buffers with greater
      valency are more effective at reducing double layer forces at low pH. Citrate
      binding at pH 6.5 leads to protein charge inversion and the formation of
      attractive electrostatic interactions. Throughout the report, we highlight
      similarities in the measured protein-protein interaction profiles with previous
      studies of globular proteins and of antibodies providing evidence that the
      behavior will be common to other protein systems. 

PMID- 25389573
TI  - Vitritis as the initial manifestation of recurrent mycosis fungoides.
AB  - PURPOSE: To report a case of mycosis fungoides in which vitritis was the earliest
      manifestation of recurrence. METHODS: A 52-year-old man was followed-up from his
      initial presentation with vitritis to his death due to recurrent mycosis
      fungoides over a 5-month period. RESULTS: The patient presented with progressive
      visual loss in the left eye. Slit-lamp examination revealed severe vitritis, and
      analysis of a vitreous fluid sample demonstrated a monomorphic population of
      abnormal T-cell lymphocytes, typical of mycosis fungoides. Three months after
      developing vitritis, the patient had extraocular recurrence of the disease, and
      he died 2 months later. CONCLUSION: Recurrent mycosis fungoides may present with
      isolated intraocular involvement.

PMID- 25389574
TI  - Neuroretinitis associated with serologies positive for bartonella henselae and
      borrelia burgdorferi.
AB  - PURPOSE: To describe a patient with neuroretinitis with features of both cat
      scratch disease and Lyme disease who had serologies positive for both Bartonella
      henselae and Borrelia burgdorferi. METHODS: Case report of a single individual
      undergoing diagnostic testing and treatment for neuroretinitis. RESULTS: A 47
      year-old woman developed acute painless loss of vision and was found to have
      neuroretinitis. Diagnostic workup yielded serologies positive for both B.
      henselae and B. burgdorferi. The patient was treated with oral antibiotics for
      coverage of both etiologies, and her condition improved. CONCLUSION: Serologies
      positive for both B. henselae and B. burgdorferi can be obtained in the workup of
      neuroretinitis. Clinicians should be aware and use clinical judgment in guiding
      their diagnosis and treatment of neuroretinitis.

PMID- 25389575
TI  - Choroidal malignant melanoma in a 6-year-old girl without melanocytosis.
AB  - PURPOSE: To describe a case of choroidal malignant melanoma in a child without
      ocular melanocytosis. METHODS: A 6-year-old girl presented with misalignment of
      the right eye of a few weeks' duration. Visual acuity was counting fingers in the
      right eye and 20/20 in the left eye. Ophthalmoscopy of the right eye revealed a
      well defined choroidal mass in the macular region measuring 10 mm in diameter
      with overlying subretinal fluid. Ultrasonography revealed that the mass was 10.1
      mm thick with choroidal excavation. On the basis of clinical and ultrasonographic
      findings, the diagnosis was choroidal melanoma without ocular melanocytosis. The
      eye was enucleated. RESULTS: Histopathologic examination revealed malignant
      melanoma of the choroid. There was not extrascleral extension. CONCLUSION:
      Choroidal malignant melanoma can occur in young patients, even in the absence of
      melanocytosis.

PMID- 25389576
TI  - Macular infarction after enterococcus faecalis endophthalmitis.
AB  - PURPOSE: To describe a case of macular infarction occurring after Enterococcus
      faecalis endophthalmitis in a patient who had undergone cataract surgery.
      METHODS: A 74-year-old woman who underwent uneventful phacoemulsification with
      intraocular lens implantation developed E. faecalis endophthalmitis on the second
      postoperative day. Management included repeated intravitreal antibiotic
      treatment, vitrectomy, and intraocular lens explantation. RESULTS: One week after
      intraocular inflammation subsided, macular infarction was noted clinically, which
      was confirmed by fundus fluorescein angiography. Visual acuity did not improve
      beyond 1/60 by Snellen chart testing. CONCLUSION: Posterior segment involvement,
      including optic atrophy, macular hole formation, and tractional retinal
      detachment, has been reported clinically as a complication of E. faecalis
      endophthalmitis. Macular infarction could be another sight-threatening
      complication of endophthalmitis due to E. faecalis.

PMID- 25389577
TI  - Orbital color Doppler imaging in embolic central retinal artery obliteration
      associated with neovascular glaucoma.
AB  - PURPOSE: To describe the detection of an embolism in the retrobulbar circulation
      using orbital color Doppler imaging (OCDI) in a patient with an inaccessible
      fundus because of neovascular glaucoma. METHODS: Review of the clinical,
      laboratory, photographic, and orbital color Doppler imaging records of a patient
      with central retinal artery occlusion (CRAO) associated with neovascular
      glaucoma. RESULTS: A 42-year-old man had no light perception in the left eye
      secondary to neovascular glaucoma. The fundus was not visible because of corneal
      edema. Orbital color Doppler imaging established the diagnosis of embolic CRAO as
      the cause of neovascular glaucoma. CONCLUSION: Orbital color Doppler imaging is
      an important diagnostic procedure for establishing CRAO as the cause of
      neovascular glaucoma when the fundus is not accessible. This noninvasive
      technology enables differentiation of embolic disease from other conditions as
      the cause of CRAO.

PMID- 25389578
TI  - Retinal arteriolar macroaneurysms overlying the optic nerve.
AB  - BACKGROUND: Retinal arteriolar macroaneurysms typically involve the second and
      third order arterioles. Macroaneurysms involving the first order arterioles,
      specifically overlying the optic nerve, have been infrequently reported. METHODS:
      This is a retrospective case series. RESULTS: Two patients were found to have an
      arteriolar macroaneurysm overlying the optic nerve. The first, a 77-year-old man,
      had focal laser photocoagulation to the macroaneurysm. The second, a 75-year-old
      woman, had spontaneous resolution of the lesion without treatment. Final visual
      acuity was 20/25 in the treated patient compared to 20/80 in the untreated
      patient. CONCLUSION: Retinal arteriolar macroaneurysms overlying the optic nerve
      will involute spontaneously or as a result of focal laser photocoagulation. The
      associated macular edema may result in permanent visual loss. Focal laser
      treatment over the optic nerve did not cause optic nerve damage.

PMID- 25389579
TI  - Proliferative retinopathy as a complication of dyskeratosis congenita.
AB  - OBJECTIVES: To describe a patient with dyskeratosis congenita (DC) who developed
      retinal neovascularization (RNV) and discuss this novel association. METHODS: A
      10-year-old boy with DC was referred for evaluation of possible retinal vascular
      disease. He underwent ophthalmologic examination, as well as fluorescein
      angiography. RESULTS: Fluorescein angiography demonstrated proliferative
      retinopathy with capillary nonperfusion in the temporal retina of both eyes. The
      patient underwent further evaluation with an examination with anesthesia and
      indirect ophthalmoscopic laser photocoagulation to areas of capillary
      nonperfusion. CONCLUSION: Although various ocular complications of both acquired
      aplastic anemia and inherited aplastic anemia due to DC have been previously
      described, to the authors' knowledge, this is the first reported case of either
      disease to exhibit RNV consistent with proliferative retinopathy.
      Ophthalmologists need to be aware of this potential complication in DC that could
      threaten vision, to provide prompt laser photocoagulation therapy.

PMID- 25389580
TI  - Chorioretinal nocardiosis.
AB  - PURPOSE: Description of ocular involvement in a case of disseminated nocardiosis.
      METHODS: Case report of an immunosuppressed patient displaying a unilateral
      extramacular choroidal lesion presumed to be due to nocardia species. The patient
      received sulfonamide treatment for a culture-proven generalized nocardia
      infection. RESULTS: During follow-up, demarcation, resolution, and secondary
      development of macular pucker with vitreoretinal traction and macular edema was
      observed. Visual acuity of the affected eye recovered from initially 20/100 to
      20/32 at the end of follow-up. CONCLUSION: Early and appropriate treatment of
      ocular endogenous nocardiosis can result in a favorable outcome.

PMID- 25389581
TI  - Vasoproliferative retinal tumor treated with indocyanine green-mediated
      photothrombosis.
AB  - PURPOSE: To assess the efficacy of indocyanine green-mediated photothrombosis
      (ICGMP) in the treatment of large vascular lesions, and in particular of a 6-mm
      large, actively exudating vasoproliferative retinal tumor (VPRT). METHODS: Thirty
      minutes after the administration of a loading dose of 1 mg/kg of intravenous ICG
      multiple, confluent, 2 mm wide, infrared 810 nm diode laser spots were applied on
      the surface of the tumor. Duration of each spot was 60 seconds, and the power
      chosen was 400 mW. A subTenon injection of 40 mg triamcinolone suspension was
      administered immediately after treatment. RESULTS: No change in tumor aspect was
      observed after treatment. ICG late images were taken, showing no perfusion of the
      lesion. Two weeks after treatment the lesion was remarkably reduced in volume,
      but residual perfusion on ICG was observed. A second treatment with three laser
      spots on the diffusion site under the same modalities was performed. After the
      second treatment a complete obliteration of the lesion could be observed. In the
      original tumor site patchy retinal pigment epithelium atrophy and hyperplasia
      appeared. A diffuse, gradual, complete resolution of the exudates is now apparent
      at the fundus. Vision has slightly improved to 20/100. Follow-up has reached 2
      years. CONCLUSION: In the presented case ICGMP achieved complete obliteration of
      a large VPRT. To our knowledge, this is the first VPRT successfully treated with
      ICGMP, and the largest retinal vascular lesion treated with laser technique
      reported in the literature. ICGMP is less invasive than cryotherapy and less
      expensive than recently proposed photodynamic therapy. It may deserve further
      study in the treatment of selected retinal vascular tumors.

PMID- 25389582
TI  - Bilateral isolated choroidal melanocytosis.
AB  - BACKGROUND: Isolated choroidal melanocytosis refers to patchy melanocytic
      choroidal hyperpigmentation without the associated scleral or cutaneous
      pigmentation seen in ocular melanocytosis or oculodermal melanocytosis. Neither
      bilateral nor diffuse cases, to our knowledge, have been previously described in
      the literature. METHODS: Case report. PATIENT: A 43-year-old woman without
      cutaneous or scleral hyperpigmentation or vitiligo was noted to have diffuse
      patchy melanocytic choroidal hyperpigmentation with feathered margins for nearly
      12 clock hours in both eyes. Large choroidal vascular sparing was noted in
      several areas. RESULTS: B-scan ultrasonography demonstrated a normal choroidal
      thickness. Cutaneous biopsy with Fontana Masson stain for melanin was within
      normal limits, without giant melanosomes. CONCLUSIONS: Isolated choroidal
      melanocytosis may present bilaterally and diffusely.

PMID- 25389583
TI  - Optical coherence tomography for precise localization of inapparent retained
      foreign body in ocular coats.
AB  - OBJECTIVE: To report the use of optical coherence tomography (OCT) for precise
      localization of inapparent, retained foreign body in ocular coats. METHODS: A 30
      year-old man presented with diminution of vision in left eye of 1 year duration.
      Visual acuity was 20/400. Ocular examination revealed a large macular hole. An
      impacted foreign body in the ocular coats was suspected and picked up with
      ultrasound B scan although orbital computed tomography scan failed to detect any
      foreign body. OCT helped in precise localization of intraocular foreign body,
      enabling its removal through the macular hole following vitrectomy. RESULTS: At 6
      weeks follow-up, macular hole was closed and visual acuity improved to 20/100,
      N36. Repeat OCT did not reveal any foreign body. CONCLUSION: OCT is a useful
      adjunct for precise localization of retained, inapparent intraocular foreign body
      in the ocular coats.

PMID- 25389584
TI  - Diffuse neonatal hemangiomatosis presenting as bilateral iris hemangiomas in an
      infant.
AB  - PURPOSE: To describe a case of diffuse neonatal hemangiomatosis presenting as
      bilateral iris hemangiomas. METHOD: Case report. PATIENT: A 2-month-old girl
      presented with bilateral enlarging red masses of her irises, congestive heart
      failure, and abdominal distension. The iris masses were diagnosed as hemangiomas,
      and she was found to have diffuse neonatal hemangiomatosis also involving her
      skin, liver, heart, and cerebellum. RESULTS: The patient's systemic hemangiomas
      were successfully treated with four cycles of weekly intravenous vincristine
      (0.05 mg/kg/dose) with concurrent resolution of her right iris hemangioma within
      6 weeks. The left iris lesion then regressed within 1 month following 1 subTenon
      injection of 20 mg of triamcinolone acetonide with residual iridocorneal
      adhesions at the site. CONCLUSION: Diffuse neonatal hemangiomatosis should be
      considered in the setting of bilateral iris hemangiomas. Also, this case
      demonstrates that iris hemangiomas associated with diffuse neonatal
      hemangiomatosis may respond to systemic vincristine, and that periocular steroids
      may be useful for treating iris hemangiomas that are unresponsive to systemic
      vincristine alone.

PMID- 25389585
TI  - Two cases of congenital simple hamartoma of the retinal pigment epithelium.
AB  - PURPOSE: Congenital simple hamartoma of the retinal pigment epithelium (CSHRPE)
      is a rare fundus condition. Two cases of CSHRPE are reported. METHODS: The
      clinical findings and biomicroscopy, fluorescein angiography, optical coherence
      tomography (OCT), and ultrasonography features differentiating this pigmented
      macular tumor from uveal melanoma or retinal pigment epithelium (RPE) anomalies
      and neoplasms are discussed. RESULTS: Two patients were observed with a pigmented
      macular lesion. Sharply demarcated transretinal lesions were seen in the macula
      of both patients, arising from the RPE. The periphery of the lesion in Case 1 was
      flat and black; the central portion was elevated and fibrotic with a central
      vitreous strand. A narrow crescent of RPE atrophy was noted temporally. Optical
      coherence tomography of both lesions showed the typical findings of CSHRPE: high
      reflectivity, irregular surface, abrupt borders, and full-thickness retinal
      shadowing. The decision was made to observe the lesions. During follow-up, the
      lesions remained unchanged. CONCLUSION: The unusual finding of CSHRPE associated
      with RPE atrophy makes the differentiation between CSHRPE and hyperplasia of the
      RPE even more difficult. Noninvasive OCT has a major role in the diagnosis of
      CSHRPE.

PMID- 25389586
TI  - 25-gauge sutureless vitrectomy in osteogenesis imperfecta type I.
AB  - PURPOSE: To report a case with type I osteogenesis imperfecta (OI) with
      intravitreal opacities who underwent 25-gauge sutureless vitrectomy. METHODS: A
      2.5-year-old girl with OI type I who presented with intravitreal opacities
      underwent 25-gauge sutureless vitrectomy. RESULTS: The 25-gauge sutureless
      vitrectomy system, which is less traumatic, was performed in a patient with OI
      type I. Nine months postoperatively, funduscopic examination under general
      anesthesia showed a healthy optic nerve and retina without detachment.
      Intraocular pressure by Tonopen was 10 mmHg. CONCLUSION: The use of 25-gauge
      sutureless vitrectomy to avoid scleral suturing and minimize surgical trauma is
      an option in pediatric patients with associated thin sclera.

PMID- 25389587
TI  - Photodynamic therapy for childhood choroidal neovascular membrane associated with
      best's vitelliform dystrophy.
AB  - PURPOSE: Subfoveal choroidal neovascular membrane is an uncommon cause of visual
      impairment in children and that caused secondary to Best's disease is a well
      known entity. However, limited experience exists in treatment of such lesions in
      the pediatric age group. This report describes the outcomes of treatment in three
      such eyes. METHODS: Three eyes of two children were treated with Verteporfin
      photodynamic therapy. One patient was observed up to 23 months and the other for
      up to 2 years. RESULTS: All three eyes were stabilized with a fair to good visual
      recovery. No ocular or systemic side effects were noted. CONCLUSION: Verteporfin
      photodynamic therapy may be a considered treatment option for childhood choroidal
      neovascular membranes secondary to Best's disease.

PMID- 25389588
TI  - Central retinal vein occlusion in primary antiphospholipid antibody syndrome.
AB  - PURPOSE: To report a case of a 20-year-old healthy patient with central retinal
      vein occlusion in his right eye attributable to primary antiphospholipid antibody
      syndrome. METHODS: A 20-year-old man with poor vision in the right eye and
      diffuse retinal hemorrhages was investigated for infections, autoimmune disease,
      diabetes, and hypertension. Testing for homocysteine, anticardiolipin antibodies,
      lupus anticoagulant, and functional assays for protein S and protein C was
      performed to detect a hypercoagulable state. RESULTS: Laboratory investigations
      revealed elevated levels of IgG and M anticardiolipin antibodies. Long-term oral
      anticoagulants were given to reduce the risk of future thromboses. CONCLUSION:
      Antiphospholipid antibodies play an important role in occlusive retinal vascular
      disorders, especially in young patients without any conventional risk factors.

PMID- 25389589
TI  - Retinal vein occlusion and papillitis in serpiginous choroidopathy.
AB  - BACKGROUND: Inflammation of the optic nerve associated with central retinal vein
      occlusion is a well-documented disorder known as papillophlebitis, which occurs
      in young adults. PURPOSE: To report two cases of serpiginous choroidopathy
      complicated by retinal vein occlusion in association with papillitis. METHODS:
      Two patients with serpiginous choroidopathy were examined during their acute and
      follow-up periods. RESULTS: One patient developed a central retinal vein
      occlusion and the other a branch retinal vein occlusion. In both cases, the
      occlusion was associated with segmental edema of the optic nerve (papillitis).
      CONCLUSION: Serpiginous choroidopathy may rarely be complicated by retinal vein
      occlusion from papillitis.

PMID- 25389590
TI  - Resolution of an abnormal preferential hyperacuity perimetry test result
      resulting from epiretinal membrane after successful surgical removal.
AB  - PURPOSE: To report resolution of an abnormal preferential hyperacuity perimetry
      test result resulting from idiopathic epiretinal membrane after successful pars
      plana vitrectomy and membrane peeling. METHODS: An observational case report.
      PATIENT: A 51-year-old otherwise healthy woman presented with a gradual decrease
      in vision and metamorphopsia in her left eye for a duration of 3 months without
      any antecedent history of ocular surgery, trauma, or disorder. RESULTS: The
      Snellen best-corrected visual acuity was 20/80 at presentation resulting from an
      epiretinal membrane on the posterior pole in the left eye. The preferential
      hyperacuity perimetry test was abnormal preoperatively but after successful pars
      plana vitrectomy and membrane peeling, the abnormality resolved completely. The
      final best-corrected visual acuity was 20/30 at 14 weeks postoperatively along
      with improvement in her metamorphopsia. CONCLUSION: Epiretinal membrane can
      produce abnormal preferential hyperacuity perimetry findings that may disappear
      after its successful surgical removal. The preferential hyperacuity perimetry may
      be useful to monitor metamorphopsia in epiretinal membrane before and after
      surgery. Further investigation is warranted.

PMID- 25389591
TI  - Retinal artery occlusion and multiple retinal deposits as a consequence of
      therapeutic arteriovenous fistula embolization.
AB  - PURPOSE: To describe a rare case of a patient who underwent a therapeutic
      arteriovenous fistula embolization and developed painful vision loss in one eye
      and to describe the clinical course, present sequential images, and propose an
      explanation. METHODS: The record of one patient with subretinal deposits,
      including fundus photographs and fluorescein angiography, was reviewed. RESULTS:
      Fundus photographs show creamy white circumscribed subretinal deposits.
      Fluorescein angiography shows evidence of retinal and choroidal ischemia.
      CONCLUSION: This patient had anomalous anatomy with an ophthalmic artery arising
      from the middle meningeal artery. This allowed the embolic material to reflux
      into the ophthalmic circulation and deposit in the retinal and choroidal
      circulation, causing infarcts.

PMID- 25389592
TI  - Simultaneous use of intravitreal viscoelastics and perfluorocarbon liquid during
      vitrectomy for severe globe rupture.
AB  - PURPOSE: To report a new method to stabilize and unfold a retinal fragment during
      vitrectomy for severe globe rupture. METHODS: Case report and intraoperative
      observations. PATIENT: A 43-year-old man with a severe globe rupture and
      extensive retinal herniation through the rupture. RESULTS: Pars plana vitrectomy
      was performed 10 days after the closure of the wound. When retinotomy was
      performed at the site of the retinal incarceration, a piece of rolled-up retina
      was seen floating around the optic disc. The retinal movement was stopped by an
      injection of viscoelastic material that filled the vitreous cavity, and then
      perfluorocarbon liquid was injected to tamponade the retina to the retinal
      pigmented epithelium. Then, the residual retinal fragment was unfolded and
      pressed against the retinal pigmented epithelium using a bimanual technique.
      After 3 years, the patient's vision recovered to hand motion under silicone oil
      tamponade. CONCLUSION: The simultaneous use of intravitreal viscoelastics and
      perfluorocarbon liquid can be used to stabilize and manipulate floating retinal
      fragments during vitrectomy after severe rupture of the globe.

PMID- 25389593
TI  - Bilateral central retinal artery occlusion in a patient with acute pancreatitis.
AB  - PURPOSE: To illustrate a case of bilateral simultaneous central retinal artery
      occlusion in a patient with acute pancreatitis. METHODS: This patient presented
      to the emergency room with a 4-day history of acute painless bilateral loss of
      vision and was then immediately referred to the on-call ophthalmologist. PATIENT:
      This patient is a 47-year-old white man with a chronic history of alcohol abuse.
      RESULTS: Laboratory workup and computed tomography abdominal imaging were
      diagnostic of acute pancreatitis. DISCUSSION: It is postulated that the resultant
      complement activation with subsequent leukoembolization along with the combined
      effect of other variables led to microvascular damage resulting in bilateral
      central retinal artery occlusion.

PMID- 25389594
TI  - Vitreomacular traction hinders the effectiveness of anti-VEGF therapy in a
      patient with exudative age-related macular degeneration.
AB  - PURPOSE: To report a case of exudative age-related macular degeneration (AMD)
      complicated by vitreomacular traction and treated with intravitreal bevacizumab.
      METHODS: Interventional case report. An 83-year-old man presented with exudative
      AMD with subretinal fluid. Optical coherence tomography (OCT) revealed
      vitreomacular traction in the left eye. The visual acuity was 20/200. Two monthly
      intravitreal injections of bevacizumab into the eye were performed; after the
      vitreomacular traction was resolved, another series of bevacizumab injections
      were given. RESULTS: After the first 2 injections of bevacizumab, OCT indicated
      that the macular appearance was unchanged, and visual acuity was reduced to
      20/250. The second series of injections resolved the submacular exudation and
      vision improved to 20/160. CONCLUSION: In this case, the presence of
      vitreomacular traction seemed to hinder resolution of submacular exudation after
      intravitreal injection of bevacizumab. The role of the vitreomacular interface in
      the effectiveness of antivascular endothelial growth factor therapy in exudative
      AMD should be considered.

PMID- 25389595
TI  - Bilateral central retinal vein occlusion in a young person with storm syndrome.
AB  - PURPOSE: To report the presence of previously undescribed retinal abnormalities
      in patients with Storm and other progeric syndromes. METHODS: Review of the
      clinical and photographic records of a patient with Storm syndrome who developed
      bilateral central retinal vein occlusion. RESULTS: A 43-year-old woman with a
      diagnosis of Storm (Werner-like) syndrome, a connective tissue disease
      characterized by premature aging, presented with bilateral nonsimultaneous
      central retinal vein occlusion. The patient was also observed to have bilateral
      peripheral retinal pigment epithelial alterations. CONCLUSION: Retinal
      abnormalities can be observed in patients with premature aging syndromes. These
      abnormalities include the development of venous occlusive disease and peripheral
      retinal pigment epithelial alterations at a relatively young age and may be
      related to the underlying genetic mutation.

PMID- 25389596
TI  - Noninfectious endophthalmitis occurring after intravitreal triesence injection.
AB  - PURPOSE: To report a case of noninfectious endophthalmitis occurring after
      intravitreal Triesence (preservative-free triamcinolone acetonide) injection.
      METHOD: Case report. RESULTS: A 62-year-old patient with macular edema occurring
      after cataract surgery received 0.1 mL (4 mg) of intravitreal Triesence to the
      left eye. His vision was 20/60. One day later, he presented with a decrease in
      vision to light perception upon awakening. He denied ocular pain, and the eye was
      not red. Clinical examination was remarkable for orbital proptosis, minimal
      fibrin on the anterior chamber intraocular lens, and a white hypopyon. There was
      no view of the retina due to vitreous opacities. A vitreous tap and injection of
      intravitreal Ceftazidime and Vancomycin were performed. Microbiology showed no
      organisms on gram stain, and the cultures were negative. The endophthalmitis
      resolved, and the patient recovered vision to 20/70. CONCLUSIONS: Noninfectious
      endophthalmitis can occur after preservative-free commercially available
      intravitreal Triesence. This case suggests that noninfectious endophthalmitis can
      occur in the absence of the benzyl alcohol found in preserved preparations of
      Kenalog.

PMID- 25389597
TI  - Intravitreal triamcinolone acetonide for cystoid macular edema secondary to
      central serous chorioretinopathy.
AB  - PURPOSE: To describe a patient with cystoid macular edema secondary to chronic
      central serous chorioretinopathy treated successfully with intravitreal
      triamcinolone acetonide. METHODS: Observational case report. RESULTS: A 66-year
      old patient presented with cystoid macular edema in his right eye 10 years after
      initial presentation with subretinal fluid from central serous chorioretinopathy.
      Cystoid macular edema was found to be unresponsive to photodynamic therapy,
      intravitreal bevacizumab, and topical nonsteroidal antiinflammatory drops. The
      patient was treated with intravitreal triamcinolone acetonide with successful
      resolution of cystoid macular edema by clinical examination and optical coherence
      tomography. Best-corrected visual acuity improved from 20/70 to 20/30 after
      treatment. CONCLUSION: Intravitreal triamcinolone acetonide was used to
      successfully treat cystoid macular edema secondary to chronic central serous
      chorioretinopathy. Treatment with local corticosteroids did not seem to worsen
      central serous chorioretinopathy in either the treated or fellow eye.

PMID- 25389598
TI  - First report in China of Enterobacteriaceae clinical isolates coharboring blaNDM
      1 and blaIMP-4 drug resistance genes.
AB  - AIMS: To describe the identification of two carbapenem-resistant, NDM-1 and IMP
      4, carbapenemases coproducing Enterobacteriaceae isolates recovered from
      hospitalized patients in China. Both Klebsiella pneumoniae clinical isolates
      (Kpn922 and Kpn9599) were resistant to meropenem and imipenem and were subjected
      to additional antibiotic susceptibility testing. Polymerase chain reaction (PCR)
      and sequence analyses were used to characterize bacterial carbapenemase
      resistance genes, extended-spectrum beta-lactamases, plasmid-mediated AmpC
      enzymes, quinolone resistance, and 16s RNA methylase. Genetic relatedness was
      determined using pulsed-field gel electrophoresis (PFGE) and multilocus sequence
      typing (MLST). Plasmids were analyzed by S1-PFGE and Southern blot. RESULTS: PCR
      analyses revealed that the Kpn922 isolate carried blaNDM-1, blaIMP-4, blaTEM-1,
      and blaSHV-1 genes, while Kpn9599 carried blaNDM-1, blaIMP-4, blaTEM-1, and
      blaSHV-12 genes. MLST determined that the two isolates were ST1043 and ST571
      sequence types. Southern blot analyses revealed that metallo-beta-lactamase genes
      were plasmid borne in both isolates. Plasmids ~300 kb simultaneously carried
      blaNDM-1 and blaIMP-4. CONCLUSIONS: Coexistence of blaNDM-1 and blaIMP-4 in these
      clinical isolates may herald the emergence of a new pattern of drug resistance.
      Surveillance of carbapenemases, particularly metallo-beta-lactamases, in
      Enterobacteriaceae is urgently needed to control and prevent the spread of these
      resistance determinants in China.

PMID- 25389599
TI  - Outpatient Ulcerative Colitis Primary Anti-TNF Responders Receiving Adalimumab or
      Infliximab Maintenance Therapy Have Similar Rates of Secondary Loss of Response.
AB  - GOALS: To compare the proportion of secondary loss of response to adalimumab and
      infliximab during maintenance treatment of ulcerative colitis (UC) after primary
      response to induction therapy. BACKGROUND: The efficacy of anti-tumor necrosis
      factor-alpha (TNF-alpha) therapy used to maintain response in patients with UC
      after primary response to induction therapy wanes with time, resulting in
      secondary loss of response. METHODS: A retrospective cohort study evaluating anti
      TNF-naive UC outpatients who were primary responders to adalimumab and infliximab
      induction therapy and who advanced onto a maintenance regimen with the respective
      anti-TNF agent from 2003 to 2013 was conducted. The primary outcome was the
      proportion of patients in each treatment group that had secondary loss of
      response. The secondary outcome was time to secondary loss of response, analyzed
      by the Kaplan-Meier method analysis. RESULTS: A total of 102 UC primary anti-TNF
      responders met inclusion criteria. Thirty-six patients (35.3%) were treated with
      adalimumab and 66 patients (64.7%) with infliximab. Mean follow-up was 139.0
      weeks for adalimumab and 158.8 weeks for infliximab. A total of 21/36 (58.3%)
      adalimumab-treated patients and 39/66 (59.1%) infliximab-treated patients
      experienced a secondary loss of response during maintenance therapy. Mean time to
      secondary loss of response was similar for adalimumab (55.8 wk) and infliximab
      (59.4 wk) (P=0.82). Sex, extent of colitis, previous or concomitant azathioprine,
      and concurrent corticosteroids with anti-TNF induction were not associated with
      increased risk of secondary loss of response. CONCLUSIONS: In this real-life
      cohort of anti-TNF-naive primary responders with UC, the proportion of secondary
      loss of response and the time to secondary loss of response are similar for
      adalimumab and infliximab.

PMID- 25389600
TI  - R173W mutation of hydroxymethylbilane synthetase is associated with acute
      intermittent porphyria complicated with rhabdomyolysis: the first report.

PMID- 25389602
TI  - Chronic central serous chorioretinopathy and fundus autofluorescence.
AB  - BACKGROUND: Chronic presentations of central serous chorioretinopathy (CSC) may
      be associated with large serous retinal detachments and subretinal exudates. The
      exudates are believed to be fibrin in acute disease and lipid in chronic
      detachments. Fundus autofluorescence (FAF) imaging has been used to study
      lipofuscin within the retinal pigment epithelium (RPE) and the integrity of the
      RPE tissue layer. METHODS: FAF imaging results for two patients with chronic CSC
      and large dependent retinal detachments were evaluated. RESULTS: As the
      detachments resolved, subretinal precipitates emerged. They were initially
      hyperautofluorescent, indicating that they were not lipid, and evolved with
      normalization of the autofluorescence but no RPE atrophy. CONCLUSION: The
      exudates beneath resolving chronic detachments are not lipid in nature, and they
      are not exclusively from lipofuscin. They are likely from fluorophores generated
      by detached photoreceptors and liberated into the subretinal space. These
      observations contribute to the knowledge of chronic CSC and the related visual
      prognosis.

PMID- 25389603
TI  - Photodynamic therapy for bilateral subfoveal choroidal neovascularization
      complicating stargardt macular dystrophy.
AB  - PURPOSE: To report the outcome of repeated photodynamic therapy (PDT) for a
      patient with choroidal neovascularization complicating Stargardt disease.
      METHODS: Interventional case report. RESULTS: A 41-year-old patient with
      Stargardt disease developed unilateral choroidal neovascularization treated
      multiple times with PDT over 2.5 years. At that time, she developed choroidal
      neovascularization in the fellow eye also treated with PDT. Despite poor interim
      vision, after >4 years of follow-up, final visual outcome was excellent.
      CONCLUSION: Our case provides further evidence that repeated PDT may be used for
      the treatment of choroidal neovascular membrane complicating Stargardt disease
      without deleterious effects up to 4 years after treatment.

PMID- 25389604
TI  - Photodynamic therapy for bilateral and simultaneous choroidal neovascularization
      in stargardt disease.
AB  - BACKGROUND: Stargardt disease may lead to chronic destructive changes to the
      retinal pigment epithelium and secondarily cause a lesion in the Bruch membrane,
      predisposing to subsequent subretinal choroidal neovascularization (CNV).
      METHODS: The authors report an angiographically documented, bilateral, and
      simultaneous case of CNV in Stargardt disease that was successfully treated with
      photodynamic therapy (PDT). RESULTS: A 53-year-old man with unequivocal Stargardt
      disease presented with CNV in both eyes simultaneously. Best-corrected visual
      acuity was 20/30 in the right eye and 20/40 in the left eye. PDT was performed in
      both eyes and vision improved to 20/25 in the right eye and 20/30 in the left
      eye. The lesions recurred 3 months later when vision had decreased to 20/40 in
      the right eye and 20/60 in the left eye. Retreatment with PDT was performed in
      both eyes and vision improved to 20/30 in the right eye and 20/50 in the left
      eye. No further recurrence was observed for 4 months. CONCLUSION: Considering the
      positive short-term outcome in this case as well as the limited data available,
      PDT may be considered in cases of CNV in Stargardt disease.

PMID- 25389605
TI  - Indocyanine green angiography in eyes with substantially increased subretinal
      fluid 1 week after photodynamic therapy.
AB  - PURPOSE: To investigate the characteristics of eyes in which a serous retinal
      detachment became substantially more extensive and persisted 1 week after
      photodynamic therapy (PDT) using indocyanine green (ICG) angiography. DESIGN:
      Retrospective, interventional case series. PATIENTS AND METHODS: The authors
      reviewed the ICG angiograms of five eyes of five patients with neovascular age
      related macular degeneration. RESULTS: In all eyes, the ICG angiograms obtained 1
      week after PDT showed a well-demarcated hypofluorescent area corresponding to the
      treatment spot. Vascular hyperpermeability emanating from the middle and large
      choroidal vessels was seen within the hypofluorescent area whether the targeted
      choroidal neovascularization was perfused or not. CONCLUSIONS: Choroidal vascular
      hyperpermeability on ICG angiography is a common finding in eyes with
      substantially increased subretinal fluid 1 week after PDT. PDT might even affect
      the middle and large choroidal vessels within the treatment spots under some
      conditions, leading to a supply of subretinal fluid and causing a persistent
      serous retinal detachment.

PMID- 25389606
TI  - Bilateral choroidal osteomas with polypoidal choroidal vasculopathy.
AB  - BACKGROUND: A choroidal osteoma is a benign osseous tumor typically arising in
      the juxtapapillary or peripapillary area. The major cause of visual loss is
      secondary to the development of a subretinal neovascular membrane. The pattern of
      neovascularization that develops with osteomas has been typically described as
      classic choroidal neovascularization (CNV). METHODS: Interventional case report.
      RESULTS: A case of bilateral polypoidal choroidal neovascularization (PCV)
      occurring with bilateral choroidal osteomas is described in a 55-year-old
      Japanese woman. To our knowledge, this variant form of vasogenesis has not
      previously been described in association with this tumor. Clinical, angiographic,
      and optical coherence tomographic features are discussed. Subretinal hemorrhage
      in the left eye from polypoidal neovascularization in the macula was successfully
      treated with photodynamic therapy. CONCLUSIONS: The association between choroidal
      osteoma and PCV may have a better prognosis than that with classic CNV.
      Indocyanine green angiography is a useful tool in characterizing the nature of
      the neovascularization.

PMID- 25389607
TI  - Intravitreal bevacizumab (avastin) and ranibizumab (lucentis) for choroidal
      neovascularization overlying choroidal osteoma.
AB  - PURPOSE: To report the effect of anti-vascular endothelial growth factor (VEGF)
      therapy for choroidal neovascularization overlying choroidal osteoma. METHOD: In
      an interventional case report, intravitreal anti-VEGF therapy was used for tumor
      related choroidal neovascularization. RESULTS: A 34-year-old woman with bilateral
      choroidal osteoma had a decrease in visual acuity in the right eye from 20/30 to
      20/100. Ophthalmoscopy revealed partially decalcified circumpapillary, macular
      choroidal osteoma with overlying subretinal hemorrhage and choroidal neovascular
      membrane. Intravitreal bevacizumab (Avastin; Genentech, Inc., South San
      Francisco, CA) resulted in membrane regression and visual acuity improvement to
      20/50 at 6 weeks. Further therapy with intravitreal ranibizumab (Lucentis;
      Genentech, Inc.) resolved persistent subretinal fluid, and visual acuity improved
      to 20/30 at the 6-month follow-up. CONCLUSIONS: Therapy with intravitreal anti
      VEGF medications might be an alternative for patients with choroidal
      neovascularization overlying choroidal osteoma.

PMID- 25389608
TI  - One-port 25-gauge pars plana vitrectomy with indirect ophthalmoscopy for
      treatment of endophthalmitis.
AB  - PURPOSE: To describe the technique and outcome of one-port transconjunctival 25
      gauge core vitrectomy with indirect ophthalmoscopy in endophthalmitis. METHODS:
      The charts of 7 patients (7 eyes) who underwent 25-gauge vitrectomy with indirect
      ophthalmoscopy for postoperative endophthalmitis were retrospectively reviewed.
      Visual outcomes, intraoperative and postoperative complications, and culture
      results were documented. RESULTS: Visual acuity improved from a mean of light
      perception before surgery to 20/100 (range, 20/25 to 20/200) at a mean follow-up
      of 24 weeks (range, 12-52 weeks). There were no operative or postoperative
      complications, except rhegmatogenous retinal detachment in one eye. CONCLUSIONS:
      One-port 25-gauge pars plana vitrectomy with indirect ophthalmoscopy is both safe
      and practical for core vitrectomy in endophthalmitis.

PMID- 25389609
TI  - Isolated ophthalmologic relapse in a case of suspected microscopic polyangiitis.
AB  - PURPOSE: To report a case of suspected microscopic polyangiitis (MPA) with
      isolated retinal vasculitis not described previously. METHODS: Case report.
      RESULTS: A 50-year-old man was admitted to the hospital because of retinal
      vasculitis. The patient had been diagnosed with systemic vasculitis type MPA 8
      years earlier. Cranial magnetic resonance imaging and transcranial Doppler
      ultrasonography did not reveal other vascular lesions. ANCA and MPO were
      detected, but results of systemic evaluation were normal. The patient was treated
      with intravenous methylprednisolone and cyclophosphamide followed by oral
      prednisone. Visual acuity improved rapidly, leading to discontinuation of
      corticosteroid therapy after 2 months. CONCLUSION: Retinal vasculitis can be a
      sign of systemic disease and, in this case, was the single manifestation of a
      relapse. In some cases of recurrent isolated retinal vasculitis, a short
      treatment course of immunosuppressive and systemic steroids can be enough for
      resolution.

PMID- 25389610
TI  - Dementia with lewy bodies and charles bonnet syndrome.
AB  - BACKGROUND: Ophthalmologists may be the first to hear about formed visual
      hallucinations in the setting of visual loss. Although such hallucinations are
      likely benign and occur in association with the Charles Bonnet syndrome, it is
      important to be aware of the strong association of hallucinations with dementia
      with Lewy bodies because the latter diagnosis is associated with significant
      prognostic and therapeutic implications for the patient. METHODS: Single case
      report. RESULTS: A patient with macular disease was presumed to have formed
      hallucinations due to the Charles Bonnet syndrome and was subsequently diagnosed
      with dementia with Lewy bodies after being admitted to a psychiatric facility.
      CONCLUSION: Both patients with the Charles Bonnet syndrome and patients with
      dementia with Lewy bodies can present with formed visual hallucinations.
      Ophthalmologists and retina specialists, in particular, should be familiar with
      the features of dementia with Lewy bodies because the diagnosis of this condition
      can allow appropriate intervention and help prevent drug-related side effects. If
      there is any suspicion of early dementia in such patients, they may benefit from
      neuropsychiatric evaluation.

PMID- 25389611
TI  - Polypoidal choroidal vasculopathy associated with tilted disk syndrome.
AB  - PURPOSE: To describe a complication of tilted disk syndrome-macular serous
      retinal detachment caused by development of polypoidal choroidal vasculopathy.
      METHODS: A 65-year-old patient with visual loss and metamorphopsia was evaluated
      with fluorescein and indocyanine green angiography (ICG) and optical coherence
      tomography. Subsequently, photodynamic therapy (PDT) with verteporfin was
      administered. RESULTS: Fundus examination showed classic features of tilted disk
      syndrome as well as a unilateral macular serous detachment secondary to a
      polypoidal lesion, which was clearly outlined by ICG angiography at the site of a
      macular lacquer crack. The lesion resolved after PDT. Two years after treatment,
      no recurrence was observed, and visual acuity was 20/25 without distortion.
      CONCLUSIONS: In this patient with tilted disk syndrome, unilateral polypoidal
      choroidal vasculopathy was diagnosed by ICG angiography and treated successfully
      with PDT.

PMID- 25389612
TI  - Acute positive titers of antibody to coxsackievirus in acute idiopathic
      maculopathy.
AB  - PURPOSE: To describe a case of acute idiopathic maculopathy (AIM) with positive
      antibody titers indicative of acute infection with coxsackievirus, the suspected
      etiology of this disorder. METHODS: A 15-year-old boy presented with acute severe
      central visual loss in the left eye after a sore throat with pustular lesions.
      Visual acuity was 20/200, and fundus examination revealed a pigmented plaque at
      the level of the retinal pigment epithelium with an overlying neurosensory
      detachment. RESULTS: Titers of antibody to coxsackievirus, measured by complement
      fixation testing, were positive for acute infection with coxsackievirus B1. Our
      treatment recommendation was observation. In a few weeks, visual acuity
      spontaneously returned to 20/20 as the exudative changes resolved leaving only a
      bull's eye-type lesion. CONCLUSION: Determination of titers of antibody to
      coxsackievirus, as shown by our case, is a useful laboratory test along with
      careful fundus biomicroscopy and history taking to confirm a clinical suspicion
      for AIM.

PMID- 25389613
TI  - Intravitreal injection of triamcinolone acetonide for serous macular detachment
      in a patient with systemic lupus erythematosus.
AB  - PURPOSE: To report our experience with intravitreal triamcinolone acetonide
      treatment of serous macular detachment in a patient with active systemic lupus
      erythematosus (SLE). METHODS: Interventional case report. RESULTS: A 38-year-old
      man who had SLE with bilateral serous macular detachment and retinopathy was
      treated with a single intravitreal injection of triamcinolone acetonide in one
      eye and two intravenous injections of a megadose steroid. Serous detachment in
      the eye injected with intravitreal steroid showed more significant improvement
      than that in the fellow eye. CONCLUSION: Our case suggests that intravitreal
      triamcinolone acetonide injection may be considered for treatment of SLE-related
      serous macular detachment that does not respond to systemic steroid therapy.

PMID- 25389614
TI  - Unilateral frosted branch angiitis in a patient with abdominal tuberculosis.
AB  - PURPOSE: To describe a case of unilateral frosted branch angiitis in a patient
      with abdominal tuberculosis. METHODS: Observational case report. RESULTS: A 17
      year-old girl with chronic abdominal pain, cough, and amenorrhea for 5 months
      presented with complaints of sudden diminution of vision in both eyes for 1 day.
      Fundus examination of the right eye showed disk edema, dilated tortuous vessels
      with perivascular sheathing (frosted branch angiitis), retinal hemorrhages, and
      macular edema. The left eye had areas of healed choroiditis. Duodenal biopsy
      showed features suggestive of tuberculosis. She was treated with antituberculosis
      therapy along with oral steroids after which the ocular condition responded
      dramatically. CONCLUSION: Frosted branch angiitis can be a rare manifestation of
      intraocular tuberculosis.

PMID- 25389615
TI  - Optic nerve macroaneurysms as the initial presentation of idiopathic retinal
      vasculitis, aneurysms, and neuroretinitis.
AB  - PURPOSE: To report a case of idiopathic retinal vasculitis, aneurysms, and
      retinitis (IRVAN) with macroaneurysms confined to the optic disk. METHODS: A
      patient with IRVAN was examined with biomicroscopy and fluorescein angiography.
      RESULTS: IRVAN typically presents with macroaneurysms along the first- and second
      order arterioles. Our patient presented with peripapillary lipid exudation and
      macroaneurysms limited to the optic nerve. The macroaneurysms were best
      appreciated with fluorescein angiography. CONCLUSIONS: This case represents an
      atypical presentation of a rare but well documented retinal vascular disorder. It
      is important to recognize the earliest possible manifestations of IRVAN to
      establish an accurate diagnosis because it may be mistaken for a wide array of
      retinal vascular and optic nerve disorders.

PMID- 25389616
TI  - Surgical management of symptomatic bullous senile retinoschisis without schisis
      detachment.
AB  - PURPOSE: To describe a rare case of bullous senile retinoschisis without schisis
      detachment in a patient who developed visual loss. METHODS: An 84-year-old woman
      presented with inferotemporal bullous senile retinoschisis from the 2:00- to 8:00
      o'clock meridians overlying the left macula. Pars plana vitrectomy, endolaser
      photocoagulation over the schisis area, and gas-fluid exchange with a 20% mixture
      of SF6 were performed. RESULTS: Complete reattachment of the inner retinal layer
      was achieved. CONCLUSION: Senile retinoschisis without schisis detachment does
      not usually require surgical management. This case shows an exceptional
      indication for surgical intervention.

PMID- 25389617
TI  - Optical coherence tomography findings in alport syndrome.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) findings of the
      macular area in patients with Alport syndrome (AS), a disease caused by mutations
      in genes coding for type IV collagen (Col4), which is the main component of the
      internal limiting membrane (ILM). METHODS: We reviewed the files for six eyes of
      three patients with AS. All patients were evaluated by OCT throughout the macula.
      RESULTS: One patient had a giant macular hole surrounded by areas of loss of
      inner retinal tissue that had grown over time. The other two patients had focal
      zones of inner retinal thinning. CONCLUSIONS: We postulate that the structural
      abnormalities of the ILM due to altered Col4 play a more important role in
      macular hole formation than hemodynamic alterations characteristic of AS. Several
      hypotheses could be expounded. Future OCT macular studies involving asymptomatic
      patients with AS would be useful in detecting and monitoring macular alterations.
      They would also contribute to a greater knowledge of this disease.

PMID- 25389618
TI  - Immediate retinal detachment after laser in situ keratomileusis.
AB  - PURPOSE: We report a case of rhegmatogenous retinal detachment immediately (first
      postoperative day) after the refractive surgery of laser in situ keratomileusis
      (LASIK). CASE REPORT: A 50-year-old man underwent bilateral LASIK; on the first
      postoperative day, he presented with decreased visual acuity due to retinal
      detachment with vitreous hemorrhage in the left eye. There were two horseshoe
      tears posterior to the equator and one peripheral operculated hole, all
      temporally located. Four months later, he presented with vitreous hemorrhage and
      a horseshoe tear temporal posterior to the equator in the right eye. RESULTS:
      Surgical treatment was done, and the retina reattached immediately after surgery
      and remained stable thereafter in both eyes. Six months after surgery, visual
      acuity was 20/30 in the left eye and 20/40 in the right eye. CONCLUSION: Although
      the cause/effect relationship between LASIK and retinal detachment has not yet
      been established, occurrence of immediate postoperative retinal detachment may
      represent a strong temporal suggestion of its association.

PMID- 25389619
TI  - Traumatic macular hole in shaken baby syndrome successfully treated with pars
      plicata vitrectomy and gas tamponade.
AB  - PURPOSE: To describe an infant with shaken baby syndrome and a traumatic macular
      hole treated with pars plana vitrectomy and gas tamponade. DESIGN: Case report.
      METHODS: A 4-month-old infant with suspected shaken baby syndrome presented with
      intraretinal and premacular hemorrhages. To prevent amblyopia, these hemorrhages
      were removed by pars plana vitrectomy, during which a full-thickness macular hole
      was discovered. Completion of a posterior vitreous detachment was not attempted
      at the time. Six months later, the macular hole remained open and was treated
      with pars plana vitrectomy, internal limiting membrane peeling, and
      perfluoropropane tamponade. RESULTS: The procedure was well tolerated, and the
      macular hole closed without postoperative positioning. The hole remained closed 6
      months after surgical repair. CONCLUSIONS: Traumatic macular hole may be a
      complication of shaken baby syndrome. This case demonstrates that pars plana
      vitrectomy with gas tamponade can be used to successfully treat traumatic macular
      hole in infants.

PMID- 25389620
TI  - Macular infarction as a presenting sign of systemic lupus erythematosus.
AB  - PURPOSE: We report two cases of macular infarction as a presenting sign of
      systemic lupus erythematosus (SLE). METHODS: Ophthalmic examination and
      intravenous fluorescein angiography were supplemented by rheumatology
      consultations and imaging. RESULTS: Two patients presented with complaints of
      decreased vision in one or both eyes. Systemic manifestations included fever,
      rash, and arthralgias, while serologic tests revealed an elevated erythrocyte
      sedimentation rate and positive antinuclear antibody titers in both cases,
      confirming the diagnosis of SLE in each case. Ophthalmoscopic changes included
      cotton-wool spots, intraretinal hemorrhages, and retinal edema. Fluorescein
      angiography revealed macular infarction with extensive retinal capillary
      nonperfusion in both patients. CONCLUSION: Macular infarction is an uncommon but
      recognized complication of vasculitis associated with SLE. We report two
      additional cases of newly diagnosed SLE where vision loss secondary to macular
      infarction was the presenting sign of the disease. SLE should be considered in
      all patients who present with macular infarction. Visual prognosis is usually
      poor.

PMID- 25389621
TI  - Intraocular cysticercosis by taenia crassiceps.
AB  - PURPOSE: The authors present a case of intraocular cysticercosis caused by Taenia
      crassiceps and provide further insight into this unusual infection. METHODS: The
      clinical, laboratory, photographic, and histopathologic records of this
      observational case report are reviewed, as are previously published cases.
      RESULTS: A healthy 14-year-old girl was referred to the retina service for
      evaluation of a total retinal detachment in her left eye. She described painless
      visual loss in this eye of 2 months' duration. The patient underwent a diagnostic
      vitrectomy to recover the organisms for identification. Thirty to forty larval T
      crassiceps cysticerci were recovered. CONCLUSION: The clustered proliferation of
      1 to 2 mm cysticerci is a distinguishing feature of intraocular cysticercosis due
      to T crassiceps. The organism can reside in the subretinal space, and may invade
      through the retina and proliferate in the vitreous cavity. When in the vitreous
      cavity, inflammation and proliferative vitreoretinopathy may ensue, leading
      within a few months to severe vision loss due to retinal detachment. Thus far,
      cases of intraocular T crassiceps have only been reported in female patients.

PMID- 25389622
TI  - Microcannula breakage in 25-gauge transconjunctival sutureless vitrectomy.
AB  - PURPOSE: To report the first case of intraoperative breakage of a microcannula
      during 25-gauge transconjunctival sutureless vitrectomy. METHOD: Case report.
      CONCLUSION: Surgeons should be aware of the potential complications of broken
      microcannulae during 25-gauge transconjunctival sutureless vitrectomy and react
      promptly to prevent further complications.

PMID- 25389623
TI  - Traumatic macular hole-related retinal detachment in an emmetropic eye
      successfully treated with vitrectomy.
AB  - PURPOSE: The authors report a case of retinal detachment in an emmetropic eye
      secondary to development of a traumatic macular hole treated by removal of the
      internal limiting membrane (ILM) with a good visual outcome. METHODS: A 13-year
      old boy was hit in his left eye by a football. The best-corrected visual acuity
      (BCVA) of the left eye was 20/40. A traumatic macular hole was present without
      posterior vitreous detachment. A retinal detachment secondary to a traumatic
      macular hole developed and BCVA decreased to 20/60 6 weeks after the injury
      Because the retinal detachment became more extensive 3 months after the injury,
      vitreous surgery was performed with creation of a posterior vitreous separation,
      followed by removal of the ILM surrounding the macular hole using 0.5%
      indocyanine green stain. Fluid-air exchange was performed followed by 20% SF6 gas
      tamponade. RESULTS: The retina was reattached and the traumatic macular hole
      closed. The VA of the left eye improved to 20/30 1 month postoperatively. No
      serious complications occurred during follow-up. CONCLUSION: Vitreous surgery
      with removal of the ILM appears to be a useful technique for treating traumatic
      macular holes with retinal detachments in emmetropic eyes and could achieve good
      visual outcomes in some cases.

PMID- 25389624
TI  - Intraocular cilium masquerading as a parasite.
AB  - BACKGROUND: Among the many different intraocular foreign bodies (IOFBs),
      eyelashes represent an uncommon finding almost invariably associated with a
      history of penetrating trauma. The authors describe a woman who had no signs and
      denied any history of trauma with an odd-looking, whitish, worm-like IOFB
      eventually identified by pathologic analysis as a cilium. CASE REPORT: A 58-year
      old lady complaining of floaters with mild loss of vision and redness presented
      to our institution. Slit-lamp examination revealed trace cells, while the fundus
      showed 1+ vitreous cells and the presence of a 3- to 4-mm-long, 0.3-mm-wide
      bright white "fluffy" wormlike object in the anterior vitreous. Medical history
      was unremarkable. The patient underwent pars plana vitrectomy with IOFB removal,
      and the specimen was sent for pathologic analysis that revealed the presence of a
      cilium encased in collagen fibers and mature adipose tissue. Vitreous cultures
      did not yield any pathogen. DISCUSSION: Eyelashes as IOFBs have been described in
      several reports and are invariably associated with penetrating trauma.
      Intraocular cilia with no apparent history of trauma have been rarely reported.
      Our patient had a very peculiar presentation because of the "fluffy" bright white
      "capsule" that although readily visible resembled a parasite more than a cilium.
      The presence of adipose tissue at the base of the cilium that may have been
      dragged with the eyelash at the time of penetration is also a matter of
      speculation.

PMID- 25389625
TI  - Aqueous misdirection syndrome after pars plana vitrectomy for retinal detachment.
AB  - BACKGROUND: Aqueous misdirection syndrome (AMS) typically occurs after surgery
      for angle closure glaucoma, or surgery in hyperopic eyes with narrow angles. Pars
      plana vitrectomy (PPV) is often considered the definitive treatment for AMS. The
      authors describe a rare case of AMS developing de novo after PPV in an eye
      without any prior history of AMS, angle closure glaucoma, or narrow angles.
      METHODS: Interventional case report. RESULTS: A 72-year-old woman with
      vitreomacular traction syndrome developed an acute rhegmatogenous retinal
      detachment and underwent an uneventful PPV, posterior hyaloid peel, cryopexy, and
      C3F8 gas insertion. Initial postoperative raised intraocular pressure (IOP) was
      successfully managed medically. She returned 6 days postoperatively with a highly
      elevated IOP refractory to medical treatments, and signs of AMS. She therefore
      underwent emergency C3F8 removal, phacoemulsification, posterior chamber IOL
      insertion, anterior vitrectomy, peripheral irido-capsulo-hyaloidectomy, and
      retamponade with 30% SF6. In 2 years of follow-up, there has been no recurrence
      of AMS and her IOP has remained normal. CONCLUSION: This case demonstrates that
      AMS can develop in vitrectomized eyes without a pre-existing history of AMS,
      angle closure glaucoma, or narrow angles. AMS should therefore be considered as a
      potential cause of raised IOP in association with a shallow anterior chamber
      following vitrectomy.

PMID- 25389626
TI  - A case of ocular toxoplasmosis: direct proof of the protozoan infection by
      retinal biopsy.
AB  - PURPOSE: To report a case of ocular toxoplasmosis with the direct evidence of
      intraocular infection of Toxoplasma gondii. METHODS: Diagnostic vitrectomy was
      performed to collect vitreous and retinal samples on a 67-year-old female patient
      who had been suffering from recalcitrant intraocular inflammation with retinal
      lesions for a year. RESULTS: Histopathological examinations of the retinal sample
      revealed numerous terminal colonies and extracellular tachyzoites that were
      confirmed to be Toxoplasma gondii by genetic analysis of vitreous and retinal
      sample using polymerase chain reaction (PCR). The intraocular disease was
      successfully treated with combination of anti-toxoplasma agents. CONCLUSION:
      Recent evolution of vitrectomy technique and genetic analysis can help
      ophthalmologists to reach more accurate diagnosis in a complicated case of ocular
      toxoplasmosis.

PMID- 25389627
TI  - Variable expressivity of abca4 gene mutations in an italian family with stargardt
      disease.
AB  - PURPOSE: Stargardt disease is a juvenile-onset macular dystrophy that can be
      inherited in an autosomal recessive manner. The gene responsible for the disease
      is ABCR, which encodes for a retinal protein. The authors report an Italian
      family with a variable expressivity of ABCR gene mutations. METHOD: Case series.
      RESULTS: ABCR mutations in both alleles were detected in two affected patients
      and in three of their healthy relatives. In this family two brothers presented a
      typical clinical picture of Stargardt disease while the third sister did not have
      any visual symptom and did not show any fundus abnormalities. Both parents seemed
      unaffected. CONCLUSIONS: This is an unusual condition that gives rise to a host
      of molecular genetics speculations.

PMID- 25389628
TI  - Reading newsprint but not headlines: pitfalls in measuring visual acuity and
      color vision in patients with bullseye maculopathy and other macular scotomas.
AB  - PURPOSE: To illustrate the confounding factors when assessing visual acuity and
      color vision in a patient with a bullseye macular scotoma in one eye and a
      horseshoe of atrophy sparing the fovea in the fellow eye. METHODS: Case report.
      Visual acuity, color vision, and scanning laser ophthalmoscope analysis. RESULTS:
      The patient with geographic atrophy from age-related macular degeneration in both
      eyes had visual acuity of 20/40- in the right eye and 20/40+ in the left eye. She
      reported that she could read newsprint but not news headlines. She could not
      identify any color plates, but had only minor errors using a color cap (large D
      15) test. She had a macular ring scotoma (bullseye scotoma) in the right eye, and
      a horseshoe-shaped area of atrophy surrounding the fovea in the fellow eye.
      CONCLUSION: Scotomas surrounding but sparing the fovea can lead to difficulty
      reading large letters, because these letters do not fit in the spared foveal
      region. Care must be taken in measuring visual acuity in these patients so that
      the testing does not stop when the patient cannot read the largest letters. The
      presence of scotomas in the central field may not allow the whole figure on color
      plate testing to be integrated and identified, leading to a possible misdiagnosis
      of cone dystrophy. Color cap testing avoids this problem.

PMID- 25389629
TI  - Effect of repetitive end-inspiration breath holding on very short-term heart rate
      variability in healthy humans.
AB  - Very short-term heart rate variability (HRV) is thought to reflect dynamic
      changes in autonomic nervous activity, which is helpful in understanding the role
      of autonomic nervous function (ANF) in the mechanisms underlying apnea-induced
      cardiac arrhythmias. The goal of this study was to investigate the effect of
      repetitive end-inspiration breath holding on very short-term HRV. A total of 32
      young healthy participants took part in the experiments. Three trials were
      performed, each involving seven repetitive end-inspiration breath holding and a
      30 s recovery period between breath holding. Durations of breath holding in the
      three trials were 1:2:3. The study first evaluated the effect of analyzed data
      lengths on the stability of HRV indices and determined three HRV indices suitable
      for very short-term analysis. The results showed that in most cases, during
      breath holding, the square root of the mean squared differences of successive
      normal RR intervals (rMSSD) was significantly lower, but normalized units of the
      power in the low frequency band ranging from 0.04 to 0.15 Hz (nLF) and LF/high
      frequency (HF) were significantly higher than those during corresponding
      durations under the normal breathing conditions. On the contrary, during recovery
      after breath holding, rMSSD was significantly higher but nLF and LF/HF were lower
      than normal. Moreover, the durations of breath holding had no significant
      influence on the variations of LF/HF. In addition, as participants repeated the
      breath holding, HRV indices varied non-linearly. HRV changes may indicate
      sympathetic activation during breath holding and parasympathetic activation
      during recovery after breath holding. In conjunction with the existing
      physiological interpretation based on changes in heart rate, the results may
      imply that breath holding leads to both cardiac sympathetic and parasympathetic
      activation simultaneously, which may be a possible pathogenic factor of apnea
      induced arrhythmias.

PMID- 25389630
TI  - Alteration in the expression of exon IIC transcripts of brain-derived
      neurotrophic factor gene by simvastatin [correction of simvastain] in chronic
      mild stress in mice: a possible link with dopaminergic pathway.
AB  - We have investigated the influence of dopaminergic agents on the expression of
      brain-derived neurotrophic factor (BDNF) gene in relation with lipid levels in
      chronic mild stress (CMS). Mice subjected to CMS were treated with simvastatin
      (10 mg/kg, per os (orally)) along with bromocriptine (2 mg/kg, intraperitoneally
      (ip)), levodopa (200 mg/kg, ip), or haloperidol (0.1 mg/kg, ip) for 14 days. CMS
      produced a decrease in sucrose intake and an increase in serum cholesterol and
      triglycerides levels with a decrease in high-density lipoprotein cholesterol,
      which were prevented by simvastatin. This was greater when it was combined with
      bromocriptine or levodopa. Haloperidol significantly prevented the simvastatin
      induced increase in sucrose intake but not the alterations in lipids. There was
      an upregulation in the expression of BDNF exon-IIA and -IIB transcripts by CMS
      but not the exon-IIC transcripts. Simvastatin could increase expression of exon
      IIC transcripts in stressed mice. This was partially increased by bromocriptine.
      Haloperidol significantly prevented simvastatin-induced increase in expression of
      BDNF exon-IIC transcripts. The results showed a positive correlation between
      expression of BDNF exon-IIC transcripts and sucrose intake. In conclusion, our
      data suggest the involvement of lipid levels and BDNF exon-IIC transcripts in CMS
      induced behaviour in mice, possibly through the dopaminergic system. 

PMID- 25389631
TI  - Tactile-direction-sensitive and stretchable electronic skins based on human-skin
      inspired interlocked microstructures.
AB  - Stretchable electronic skins with multidirectional force-sensing capabilities are
      of great importance in robotics, prosthetics, and rehabilitation devices.
      Inspired by the interlocked microstructures found in epidermal-dermal ridges in
      human skin, piezoresistive interlocked microdome arrays are employed for stress
      direction-sensitive, stretchable electronic skins. Here we show that these arrays
      possess highly sensitive detection capability of various mechanical stimuli
      including normal, shear, stretching, bending, and twisting forces. Furthermore,
      the unique geometry of interlocked microdome arrays enables the differentiation
      of various mechanical stimuli because the arrays exhibit different levels of
      deformation depending on the direction of applied forces, thus providing
      different sensory output patterns. In addition, we show that the electronic skins
      attached on human skin in the arm and wrist areas are able to distinguish various
      mechanical stimuli applied in different directions and can selectively monitor
      different intensities and directions of air flows and vibrations. 

PMID- 25389632
TI  - Penetrance and clinical features of pheochromocytoma in a six-generation family
      carrying a germline TMEM127 mutation.
AB  - CONTEXT: The phenotype of familial pheochromocytoma (PHEO) associated with
      germline TMEM127 mutations (TMEM127-related PHEO) has not been clearly defined.
      OBJECTIVE: This study aimed to investigate the penetrance, full phenotypic
      spectrum and effectiveness of clinical/genetic screening in TMEM127-related PHEO.
      DESIGN, SETTING, AND PARTICIPANTS: Clinical and genetic screening, and genetic
      counseling were offered to 151 individuals from a six-generation family carrying
      a TMEM127 germline mutation in a referral center. INTERVENTION AND MAIN OUTCOME
      MEASURES: TMEM127 genetic testing was offered to at-risk relatives and clinical
      surveillance for pheochromocytoma was performed in mutation-positive carriers.
      RESULTS: Forty seven individuals carried the c.410-2A>C TMEM127 mutation.
      Clinical data were obtained from 34 TMEM127-mutation carriers followed up for 8.7
      +/- 8.1 years (range, 1-20 y). Pheochromocytoma was diagnosed in 11 carriers
      (32%) at a median age of 43 years. In nine patients, symptoms started at 29 years
      (range, 10-55 y) and two cases were asymptomatic. Tumors were multicentric in
      five (45%) and bilateral in five (45%) patients. Six patients (54%) had at least
      one adrenomedullary nodule less than 10 mm. No paragangliomas, distant
      metastases, or other manifestations were detected. Cumulative penetrance of
      pheochromocytoma was 0% at 0-20 years, 3% at 21-30 years, 15% at 31-40 years, 24%
      at 41-50 years, and 32% at 51-65 years. The youngest case was diagnosed at 22
      years and the earliest symptoms were reported at age 10. CONCLUSIONS: Tumor
      multicentricity, nodular adrenomedullary hyperplasia, and the occurrence of
      symptoms more than a decade earlier than the age at diagnosis are novel findings
      in TMEM127-related PHEO. The high penetrance of pheochromocytoma in this
      condition validates the benefits of genetic testing of at-risk relatives. We thus
      recommend that TMEM127 genetic testing should be offered to at-risk individuals
      at age 22 years and mutation carriers should undergo clinical surveillance
      annually.

PMID- 25389633
TI  - Novel heat shock protein 90 inhibitor NVP-AUY922 synergizes with the histone
      deacetylase inhibitor PXD101 in induction of death of anaplastic thyroid
      carcinoma cells.
AB  - CONTEXT: The influence of the novel heat shock protein 90 (hsp90) inhibitor NVP
      AUY922 (AUY922) on anaplastic thyroid carcinoma (ATC) cells has not been
      investigated. OBJECTIVE: The effect of AUY922 alone or in combination with the
      histone deacetylase inhibitor PXD101 on survival of ATC cells was evaluated.
      RESULTS: In ATC cells, AUY922, compared with 17-allylamino-17
      demethoxygeldanamycin, herbimycin A and radicicol, potently lead to growth
      inhibition and cell death with cleavage of caspase-3 and poly (ADP-ribose)
      polymerase (PARP) and concomitant changes in expression of hsp90 client proteins.
      After treatment of both AUY922 and PXD101, compared with treatment of AUY922 or
      PXD101 alone, the percentage of nonviable cells, annexin V-stained cells, and
      cytotoxic activity increased. All of the combination index values were lower than
      1.0, suggesting the synergism between AUY922 and PXD101 in induction of cell
      death. In cells treated with both AUY922 and PXD101, compared with cells treated
      with AUY922 alone, the protein levels of phospho-Akt, cellular inhibitor of
      apoptosis protein, X-linked inhibitor of apoptosis protein, survivin, ataxia
      telangiectasia mutated (ATM), and ATM and Rad-3 related (ATR) decreased, whereas
      those of acetyl. histone H3, acetyl. histone H4, phospho-histone H2A.X, cleaved
      DFF45, and cleaved PARP increased. CONCLUSION: Our results demonstrate that
      AUY922 potently induces cytotoxicity with concomitant modulation of hsp90 client
      proteins in ATC cells. Moreover, AUY922 has a synergistic activity with PXD101 in
      induction of cytotoxicity in conjunction with the inactivation of PI3K/Akt
      signaling and survivin and the activation of DNA damage response in ATC cells.

PMID- 25389634
TI  - Age-related maximal heart rate: examination and refinement of prediction
      equations.
AB  - AIM: The aim of this study was to establish the maximal heart rate (HRmax)-age
      relation with minimal error rate. METHODS: The records of 28,137 participants
      (20,691 male and 7446 female, age range between 10 and 80 yrs) who performed a
      maximal stress test were used in this study. Linear regressions between HRmax and
      age were used for the entire sample, for the male and female samples, separately,
      and for each section of the gender-by-age category. The equations were then
      contrasted to a number of equations reported in the literature. The best fitted
      equations were then tested on a new sample of 2449 subjects (2091 males and 358
      females) for validation purposes. RESULTS: Mean HRmax values were found to
      decrease at a faster rate in women than in men with age increase. The linear
      regression functions within each age category were found to be less reliable than
      the equations derived for the entire sample and for the female and male samples,
      respectively. The new and updated HRmax prediction equations are as follows:
      HRmax=208.609-0.716age and 209.273-0.804age for males and females, respectively,
      and 208.852-0.741age for the entire sample. Those equations along with the other
      four best equations for predicting HRmax were found to be correlated with the
      observed HRmax values (validation sample): 0.64 and 0.664 for males and females,
      respectively. CONCLUSION: Our equations were derived from a large data set and
      were found to be highly sensitive for both genders. Therefore, we propose that
      these new formulas, with their improved accuracy, be used in healthy active and
      clinical populations.

PMID- 25389635
TI  - Reproducibility of cycling at 110% peak power output: methodological concern.

PMID- 25389636
TI  - Individual anaerobic threshold estimates maximal lactate steady state in
      temperate and hot climate.
AB  - BACKGROUND: The aim of the present study was to compare the power output at the
      maximal lactate steady state (MLSS) with the power output at the individual
      anaerobic threshold (IAT) and at the onset of blood lactate accumulation (OBLA)
      in both temperate (TEMP) (22  degrees C) and hot (HOT) (40  degrees C) climates.
      METHODS: Eight young active male (23.9+/-2.4 yr, 75.9+/-7.3 kg and 47.8+/-4.9
      mL/kg/min) were evaluated on a cycle ergometer and performed a progressive
      exercise test until fatigue to determine the IAT and OBLA and two to five 30-min
      exercise tests at constant intensities for determine MLSS at both temperatures.
      An ANOVA with repeated measures and Dunnett's post-hoc test was performed to
      compare results of IAT and OBLA to the variables at the MLSS in both climates
      with MLSS being considered as the standard. RESULTS: At TEMP there was no
      difference between the power output at MLSS and IAT (180+/-11 W and 182+/-13 W,
      respectively), however, the intensity of the OBLA (154+/-11 W) was lower than
      MLSS (P<0.05). At HOT there was no difference between the power output at MLSS,
      IAT, and OBLA (148+/-11 W, 155+/-12 W and 144+/-11 W, respectively). CONCLUSIONS:
      These results showed that IAT is sensitive enough to estimate MLSS in both TEMP
      and HOT climate.

PMID- 25389637
TI  - Changes to circulating inflammatory cytokines in response to moderate exercise.
AB  - BACKGROUND: Regular physical activity improves the metabolic profile of patients,
      although the biological mechanisms involved are not clear yet. The anti
      inflammatory effects of exercise are well known and are possibly related to its
      therapeutic properties. The aim of this study was to compare changes in the
      concentration of an anti-inflammatory cytokine - tumor necrosis factor soluble
      receptor-1 (sTNFR1) - and a pro-inflammatory cytokine - interleukin-1beta (IL
      1beta) - during moderate physical exercise in sedentary versus athletic men.
      METHODS: We analyzed serum inflammatory cytokine concentrations in 5 athletes and
      5 sedentary men (aged 18 to 22): 1) 15 minutes and immediately before a 28-minute
      specifically-programmed moderate exercise session; 2) every 3 minutes during the
      exercise session; 3) 15 and 30 minutes after session completion. RESULTS: We
      obtained serum sTNFR1 and IL-1beta concentrations in 10 individuals. Both
      cytokines exhibited changes in their concentration during physical exercise: a
      significant increase in the concentration of sTNFR1 was observed in both the
      sedentary (P=0.0249) and the athlete (P=0.02172) groups. The levels of sTNFR1
      were higher in the athlete group than in the sedentary group. No differences were
      observed in the IL-1beta concentrations between the two groups. CONCLUSIONS:
      Serum concentration of the anti-inflammatory cytokine sTNFR1 increased during
      moderate physical exercise, and its levels were higher in athletes before, during
      and after physical activity. These findings are consistent with previous findings
      concerning the anti-inflammatory properties of exercise, and suggest that sTNFR1
      has an important role in the anti-inflammatory environment following physical
      activity.

PMID- 25389638
TI  - Pathological changes in the lumbar intervertebral discs among professional field
      hockey players.
AB  - BACKGROUND: Acute injuries or chronic overloading can be the cause of lower back
      pain. Long-term, highly-specialized training can cause the musculoskeletal system
      to become overloaded. Field hockey is an example of a sport which, due to the
      players' non-ergonomic positions, can lead to degenerative changes in the lumbar
      spine. METHODS: The aim of this study was to evaluate the condition of the lumbar
      spine among 20 male players of the Polish national team in field hockey, aged
      between 24 and 35 years of age, and having trained in the discipline of field
      hockey for a period of between 14 and 26 years. CT scans were used to determine
      the height of vertebrae and intervertebral discs. RESULTS: The study showed a
      number of differences in lumbar discs and vertebrae that are typical results of
      overloading. A significant decrease in disc height was observed, as well as
      changes in the shape of the vertebrae, which acquired a wedge shape. Analysis of
      the Relative Height Coefficient showed that these changes are both severe and
      exacerbated by years of training. CONCLUSIONS: This research proves that field
      hockey as an active sport strongly affects the lumbar section of the spine. As a
      therapeutic procedure, a special regime including muscle stretching and lumbar
      spine stabilization exercises should be created for both advanced and beginner
      players.

PMID- 25389639
TI  - Physical and physiological characteristics of male handball players: influence of
      playing position and competitive level.
AB  - BACKGROUND: The purpose of this study was to quantify differences in
      anthropometrical and physical characteristics according to playing position and
      competitive level in male elite handball. METHODS: One hundred and seventy-six
      national team and 1st division players (age 23+/-4 years, body mass 89+/-11 kg,
      body height 188+/-5 cm) participated in the study. All participants were tested
      on throwing velocity, 20-meter sprint, countermovement jump, 3000-meter run, 1RM
      squat and bench press. RESULTS: Back players achieved higher throwing velocities
      compared to other positions. National team back players achieved higher
      velocities in set shots (9.4%, P<0.001, d=1.5) and jump shots (8.1%, P<0.001,
      d=1.5) than 1st division players. Wings sprinted faster than pivots (3.5%,
      P<0.001, d=1.2) and goalkeepers (5.4%, P<0.001, d=1.2). Wings jumped higher than
      pivots (13.0%, P<0.001, d=1.0) and goalkeepers (11.4%, P=0.003, d=0.9). National
      team back players ran faster than 1st division back players over 3000 meters
      (4.9%, P=0.011, d=0.7). Back players showed better relative strength in squat
      than pivots (12.1%, P=0.016, d=0.7). Wings had better relative strength in squat
      that pivots (17.4%, P=0.001, d=1.0) and goalkeepers (13.1%, P=0.016, d=0.8).
      Pivots were 8.9% stronger than wing players (P=0.044, d=0.7) in 1RM bench press.
      CONCLUSIONS: Varying on-court demands in handball are reflected by different
      physical and physiological characteristics across playing standard and positions.
      Physical conditioning of players should therefore be individualized and targeted
      to solve the position-dependent tasks during play.

PMID- 25389640
TI  - Generic and sport-specific reactive agility tests assess different qualities in
      court-based team sport athletes.
AB  - BACKGROUND: Comparisons between reactive agility tests incorporating generic and
      sport-specific stimuli have been performed only in field-based team sports. The
      aim of this study was to compare generic (light-based) and sport-specific (live
      opponent) reactive agility tests in court-based team sport athletes. METHODS:
      Twelve semi-professional male basketball players (age: 25.9+/-6.7 yr; stature:
      188.9+/-7.9 cm; body mass: 97.4+/-16.1 kg; predicted maximal oxygen uptake:
      49.5+/-5.3 mL/kg 7 min) completed multiple trials of a Reactive Agility Test
      containing light-based (RAT-Light) and opponent-based stimuli (RAT-Opponent).
      Multiple outcome measures were collected during the RAT-Light (agility time and
      total time) and RAT-Opponent (decision time and total time). RESULTS: Mean
      performance times during the RAT-Light (2.233+/-0.224 s) were significantly
      (P<0.001) slower than during the RAT-Opponent (1.726+/-0.178 s). Further, a small
      relationship was observed between RAT-Light agility time and RAT-Opponent
      decision time (r10=0.20), while a trivial relationship was apparent between total
      performance times across tests (r10=0.02). Low commonality was observed between
      comparable measures across tests (R2=0-4%). CONCLUSIONS: Reactive agility tests
      containing light-based and live opponent stimuli appear to measure different
      qualities in court-based team sport athletes. Court-based team sport coaches and
      conditioning professionals should not use generic and sport-specific reactive
      agility tests interchangeably during athlete assessments.

PMID- 25389641
TI  - Factors associated with small abdominal aortic aneurysm expansion rate.
AB  - IMPORTANCE: Because of the high mortality rate after rupture of small abdominal
      aortic aneurysms (AAAs), surveillance is recommended to detect aneurysm
      expansion; however, the effects of clinical risk factors on long-term patterns of
      AAA expansion are poorly characterized. OBJECTIVE: To identify significant
      clinical risk factors associated with the AAA expansion rate for both constant
      and accelerated expansion trajectories. DESIGN, SETTING, AND PARTICIPANTS: A
      multivariate mixed-effects model was established to identify clinical risk
      factors associated with the AAA expansion rate. Separate shape factor analysis
      was used to characterize steady vs accelerated expansion over time. Five hundred
      sixty-seven patients hospitalized at Veterans Affairs medical centers were
      randomized to the surveillance arm of the Aneurysm Detection and Management
      (ADAM) study conducted by the Veterans Affairs Cooperative Studies Program from
      1992 to 2000. The patients had an AAA with a maximum diameter from 3.0 to 5.4 cm,
      which was monitored until a 5.5-cm maximum diameter was reached or the aneurysm
      became symptomatic. Thirty-three participants were not included in this analysis
      owing to missing or extraneous values in key predictor variables. The mean (SD)
      follow-up time was 3.7 (2.0) years. MAIN OUTCOMES AND MEASURES: The primary
      outcome measure was the AAA expansion rate, determined by measurement of the
      maximum diameter by ultrasonography at regular intervals. The objective to assess
      the association of clinical variables with the expansion of the AAA was
      formulated after data collection. RESULTS: The mean (SD) linear expansion rate of
      AAAs was 0.26 (0.01) cm/y. Current smoking was associated with a 0.05 (0.01)-cm/y
      increase in the linear expansion rate (95% CI, 0.25-0.28; P < .001), diastolic
      blood pressure with a 0.02 (0.01)-cm/y increase per 10 mm Hg (95% CI, 0.01-0.04;
      P = .001), and diabetes mellitus with a 0.11 (0.02)-cm/y decrease (95% CI, 0.07
      0.16; P < .001). Diastolic blood pressure and baseline AAA diameter were
      associated with accelerated AAA expansion (P = .001 and P < .001, respectively).
      CONCLUSIONS AND RELEVANCE: Smoking cessation and control of diastolic blood
      pressure are direct actions that should be taken to reduce the rate of AAA
      expansion. Other clinical risk factors, except for diabetes, were not associated
      with the AAA expansion rate. This study also provides evidence of differing
      trajectories in AAA expansion over time, a finding that merits further
      investigation.

PMID- 25389642
TI  - Correcting Bias Caused by Missing Data in the Estimate of the Effect of
      Apolipoprotein epsilon4 on Cognitive Decline.
AB  - Longitudinal administration of neuropsychological instruments are often used to
      assess age-related changes in cognition. Informative loss to follow-up may bias
      the results of these studies. Herein, we use auxiliary data to adjust for
      informative loss to follow-up. In the Einstein Aging Study, memory was assessed
      annually in a community sample of adults age 70+, free of dementia at baseline,
      using the free recall from the Free and Cued Selective Reminding Test, and via
      telephone using the Memory Impairment Screen for Telephone (the auxiliary data).
      Joint linear mixed models were used to assess how the effect of the APOE epsilon4
      genotype may be affected by informative missingness in the in-person data. A
      total of 620 EAS participants contributed 2085 person years of follow-up to the
      analyses. Memory decline rates estimated in joint models were 19% greater in
      epsilon4 negative participants and 27% greater in epsilon4 positive participants
      compared to traditional approaches; the effect of APOE epsilon4 on memory decline
      was 37% greater. Joint modeling methods can help address bias caused by
      informative missing data in the estimation of the effect of risk factors on
      cognitive change, and may be applicable to a broader range of outcomes in
      longitudinal aging studies.

PMID- 25389643
TI  - Allosteric regulation of supramolecular oligomerization and catalytic activity
      via coordination-based control of competitive hydrogen-bonding events.
AB  - Herein, we demonstrate that the activity of a hydrogen-bond-donating (HBD)
      catalyst embedded within a coordination framework can be allosterically regulated
      in situ by controlling oligomerization via simple changes in coordination
      chemistry at distal Pt(II) nodes. Using the halide-induced ligand rearrangement
      reaction (HILR), a heteroligated Pt(II) triple-decker complex, which contains a
      catalytically active diphenylene squaramide moiety and two hydrogen-bond
      accepting (HBA) ester moieties, was synthesized. The HBD and HBA moieties were
      functionalized with hemilabile ligands of differing chelating strengths, allowing
      one to assemble them around Pt(II) nodes in a heteroligated fashion. Due to the
      hemilabile nature of the ligands, the resulting complex can be interconverted
      between a flexible, semiopen state and a rigid, fully closed state in situ and
      reversibly. FT-IR spectroscopy, (1)H DOSY, and (1)H NMR spectroscopy titration
      studies were used to demonstrate that, in the semiopen state, intermolecular
      hydrogen-bonding between the HBD and HBA moieties drives oligomerization of the
      complex and prevents substrate recognition by the catalyst. In the rigid, fully
      closed state, these interactions are prevented by steric and geometric
      constraints. Thus, the diphenylene squaramide moiety is able to catalyze a
      Friedel-Crafts reaction in the fully closed state, while the semiopen state shows
      no reactivity. This work demonstrates that controlling catalytic activity by
      regulating aggregation through supramolecular conformational changes, a common
      approach in Nature, can be applied to man-made catalytic frameworks that are
      relevant to materials synthesis, as well as the detection and amplification of
      small molecules. 

PMID- 25389644
TI  - Proteomic basis of stress responses in the gills of the pacific oyster
      Crassostrea gigas.
AB  - The Pacific oyster Crassostrea gigas is one of the dominant sessile inhabitants
      of the estuarine intertidal zone, which is a physically harsh environment due to
      the presence of a number of stressors. Oysters have adapted to highly dynamic and
      stressful environments, but the molecular mechanisms underlying such stress
      adaptation are largely unknown. In the present study, we examined the proteomic
      responses in the gills of C. gigas exposed to three stressors (high temperature,
      low salinity, and aerial exposure) they often encounter in the field. We
      quantitatively compared the gill proteome profiles using iTRAQ-coupled 2-D LC
      MS/MS. There were 3165 identified proteins among which 2379 proteins could be
      quantified. Heat shock, hyposalinity, and aerial exposure resulted in 50, 15, and
      33 differentially expressed gill proteins, respectively. Venn diagram analysis
      revealed substantial different responses to the three stressors. Only xanthine
      dehydrogenase/oxidase showed a similar expression pattern across the three stress
      treatments, suggesting that reduction of ROS accumulation may be a conserved
      response to these stressors. Heat shock caused significant overexpression of
      molecular chaperones and production of S-adenosyl-l-methionine, indicating their
      crucial protective roles against protein denature. In addition, heat shock also
      activated immune responses, Ca(2+) binding protein expression. By contrast,
      hyposalinity and aerial exposure resulted in the up-regulation of 3
      demethylubiquinone-9 3-methyltransferase, indicating that increase in ubiquinone
      synthesis may contribute to withstanding both the osmotic and desiccation stress.
      Strikingly, the majority of desiccation-responsive proteins, including those
      involved in metabolism, ion transportation, immune responses, DNA duplication,
      and protein synthesis, were down-regulated, indicating conservation of energy as
      an important strategy to cope with desiccation stress. There was a high
      consistency between the expression levels determined by iTRAQ and Western
      blotting, highlighting the high reproducibility of our proteomic approach and its
      great value in revealing molecular mechanisms of stress responses. 

PMID- 25389645
TI  - Investigation of natural lipid-phenolic interactions on biological properties of
      virgin olive oil.
AB  - There is limited knowledge regarding the impact of naturally occurring lipid
      phenolic interactions on the biological properties of phenolics in virgin olive
      oil. Free and bound phenolics were isolated via sequential methanolic extraction
      at 30 and 60  degrees C, and were identified and quantified using reversed phase
      high performance liquid chromatography, liquid chromatography coupled to tandem
      mass spectrometry (LC-MS/MS), and gas chromatography. Decreased oleic acid
      concentrations and increased concentrations of palmitoleic acid, stearic,
      linoleic, and linolenic acids were observed in virgin olive oil after removal of
      free and bound lipid phenolic compounds. The presence of p-hydroxybenzoic acid
      and tyrosol bound to glycerides was determined via LC-MS/MS, which indicates
      natural lipid-phenolic interactions in virgin olive oil. Both free and lipid
      bound phenolic extracts exerted antiproliferative activities against the CRC1 and
      CRC5 colorectal cancer cell lines. The present work indicates that naturally
      occurring lipid-phenolic interactions can affect the biological properties of
      phenolics in virgin olive oil. 

PMID- 25389646
TI  - Contact force-sensing catheters.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent research
      findings in contact force-sensing radiofrequency ablation catheters. RECENT
      FINDINGS: Contact force parameters evaluated during pulmonary vein isolation for
      treating atrial fibrillation correlated well with the presence of gaps in the
      wide area circumferential ablation lines at 3 months, decreased procedural times,
      and improved clinical outcome at 1 year. The contact force during pulmonary vein
      isolation should be a target of 10-20 g of force and a minimum force-time
      integral of 400 g/s for each new lesion. In the ventricle, contact force varied
      depending on whether a transseptal versus retrograde aortic approach was
      utilized: contact force use yielded more visible ablation lesions at necropsy.
      SUMMARY: Contact force-sensing catheters have demonstrated improved outcome after
      catheter ablation of atrial fibrillation. Future studies will focus on
      ventricular tachycardia ablation; preliminary data suggest more durable lesions
      with contact force-sensing catheters. Contact force catheters may enhance
      academic training by giving real-time feedback regarding catheter contact,
      increase safety, and may lead to a resurgence in remote navigation ablation
      systems.

PMID- 25389647
TI  - Long-term oral anticoagulation for patients after successful catheter ablation of
      atrial fibrillation: is it necessary?
AB  - PURPOSE OF REVIEW: Catheter ablation for atrial fibrillation is an effective
      rhythm-control therapy for selected patients. Currently, it is unknown whether
      maintenance of sinus rhythm after atrial fibrillation ablation can reduce one's
      stroke risk. If so, this may potentially obviate the need to treat patients with
      long-term oral anticoagulation (OAC). This article reviews the available evidence
      and areas of uncertainty pertaining to this question. RECENT FINDINGS: To date,
      no randomized trial data exist on this topic. Analyses from health administrative
      databases and observational registries suggested that atrial fibrillation
      patients who underwent catheter ablation had lower risk of stroke when compared
      with those who did not. Among patients who maintained sinus rhythm after
      ablation, low rates of stroke (<0.7% per year) were observed even after
      discontinuation of OAC therapy. These findings raise the possibility that
      successful catheter ablation may lower one's stroke risk to a point at which long
      term OAC therapy is not obligatory. SUMMARY: Whether successful atrial
      fibrillation ablation reduces one's stroke risk is unknown. Low stroke risks were
      reported by observational studies in patients who maintained sinus rhythm after
      ablation despite OAC cessation. High-quality, randomized trial data are needed to
      provide clarity on this key unanswered question.

PMID- 25389648
TI  - Management of outflow tract ventricular arrhythmias.
AB  - PURPOSE OF REVIEW: Outflow tract ventricular arrhythmias represent an important
      chapter in clinical electrophysiology. Recent investigations enhance the
      knowledge in that field and highlight new important concepts in ventricular
      arrhythmogenesis. RECENT FINDINGS: Recent publications have revealed new
      interesting results in the field of outflow tract ventricular arrhythmias. The
      embryonic phenotype is maintained in the adult outflow tract, which leads to
      conduction slowing in some circumstances. Outflow tract ventricular arrhythmias
      unrelated to any detectable abnormal area may happen in structural heart disease.
      Promising results are expected using noninvasive high-density ECG mapping for
      outflow tract ventricular arrhythmia localization. In an experimental model of
      Brugada syndrome, late fractionated activity at the outflow tract was shown to
      result from repolarization heterogeneity. Malignant ventricular arrhythmias from
      the right ventricular outflow tract should be suspected in case of syncopal
      episode and when ectopies display a positive QRS complex in lead I. Ablation was
      shown to be superior to drug therapy for outflow tract ventricular arrhythmia in
      a recent prospective randomized study. Recent reports described novel previously
      unsuspected locations for ventricular arrhythmia, while some still poorly
      recognized structures are implicated in outflow tract ventricular arrhythmia.
      SUMMARY: Recent findings have shed new light on the basic and clinical
      electrophysiology of the outflow tract, which may enhance the management of
      patients with benign outflow tract ventricular arrhythmia and solve the complex
      relationships between outflow tract ventricular arrhythmia and sudden death.

PMID- 25389649
TI  - Rotor mapping and ablation to treat atrial fibrillation.
AB  - PURPOSE OF REVIEW: Rotors have long been postulated to drive atrial fibrillation,
      but evidence has been limited to animal models. This changed recently with the
      demonstration using focal impulse and rotor modulation (FIRM) mapping that rotors
      act as human atrial fibrillation sources. This mechanistic approach to diagnosing
      the causes of atrial fibrillation in individual patients has been supported by
      substantially improved outcomes from FIRM-guided ablation, resulting in increased
      attention to rotors as therapeutic targets. RECENT FINDINGS: In this review, we
      outline the pathophysiology of rotors in animal and in-silico studies of
      fibrillation, and how this motivated FIRM mapping in humans. We highlight the
      characteristics of rotors in human atrial fibrillation, now validated by several
      techniques, with discussion on similar and discrepant findings between
      techniques. The interventional approaches to eliminate atrial fibrillation rotors
      are explained and the ablation results in latest studies using FIRM are
      discussed. SUMMARY: We propose that mapping localized sources for human atrial
      fibrillation, specifically rotors, is moving the field towards a unifying
      hypothesis that explains several otherwise contradictory observations in atrial
      fibrillation management. We conclude by suggesting areas of potential research
      that may reveal more about these critical sites and how these may lead to better
      and novel treatments for atrial fibrillation.

PMID- 25389650
TI  - Surgical ablation for atrial fibrillation: techniques, indications, and results.
AB  - PURPOSE OF REVIEW: The aim of this review is to focus specifically on the
      indications, evolution of technique, and results of surgical ablation for atrial
      fibrillation. RECENT FINDINGS: With the introduction of the Cox-Maze IV procedure
      utilizing bipolar radiofrequency ablation and cryoablation, long-term studies
      have demonstrated a significant decrease in aortic cross-clamp times and major
      complications with a comparable rate of restoration of sinus rhythm. New hybrid
      approaches utilizing both catheter-based ablation and minimally invasive surgical
      approaches have been developed, but have not been standardized. Early studies
      have demonstrated reasonable success rates of hybrid procedures, with advantages
      that include confirmation of conduction block, decreased surgical morbidity, and
      possibly reduced morbidity. However, hybrid approaches have the disadvantage of
      significantly increased operative times. SUMMARY: The Cox-Maze IV is currently
      the gold standard for surgical treatment of atrial fibrillation. New hybrid
      approaches have potential advantages with promising early results, but a standard
      lesion set, improvement in operative times, and long-term results still need to
      be evaluated.

PMID- 25389651
TI  - Fetal intervention for critical aortic stenosis: advances, research and postnatal
      follow-up.
AB  - PURPOSE OF REVIEW: Fetal aortic valvuloplasty is intended to alter the natural
      history of aortic stenosis evolving to hypoplastic left heart syndrome. The most
      recently reported data and advances on this procedure were reviewed. RECENT
      FINDINGS: The highlights of the latest experience are the advances in further
      understanding of the prenatal and postnatal natural history of this disease, and
      the way in which fetal aortic valvuloplasty impacts on it, the identification of
      new predictors of biventricular outcome, and the report of postnatal survival of
      intervened patients. Recently reported short-term and middle-term results are
      encouraging. Experimental research on procedural aspects is ongoing, with no
      definite results. Multicenter studies are also ongoing. SUMMARY: In recent years,
      there have been advances in the understanding of the prenatal and postnatal
      process of aortic stenosis evolving to hypoplastic left heart syndrome and the
      effects of fetal aortic valvuloplasty, as well as the need of adequate postnatal
      therapeutic strategies for these patients. Procedural aspects are being studied
      with animal models, but still need far more experience before human application.
      Long-term results are still to be discovered, and multicenter studies may provide
      a new perspective. Continuing research is mandatory so that ultimately fetal
      heart intervention finds its place among the therapeutic resources for congenital
      heart disease.

PMID- 25389652
TI  - A practical guide to early repolarization.
AB  - PURPOSE OF REVIEW: Early repolarization has been associated in the past decade
      with idiopathic ventricular fibrillation and arrhythmic death. The purpose of
      this review is to clarify recent changes in the definition of early
      repolarization and provide a practical approach to patients with this
      electrocardiographic sign. RECENT FINDINGS: Recent population studies have
      associated early repolarization with arrhythmic death. Challenges remain,
      however, in interpreting the risk of the early repolarization
      electrocardiographic pattern, as it is a common finding in the general population
      with a prevalence of 3-13%. Early repolarization characteristics associated with
      an especially high risk include high-amplitude J-point elevation,
      horizontal/descending ST segment, and inferior lead location.In view of the
      association of early repolarization with sudden death, a syndrome termed 'early
      repolarization syndrome' (ERS) has been accepted as the latest 'channelopathy' in
      patients with cardiac arrest, pronounced early repolarization pattern, and an
      otherwise structurally normal heart.The physiological basis of early
      repolarization is thought to involve an electrical transmural gradient produced
      by the transient outward current. Recent genetic studies have associated
      mutations in genes contributing to this current and other ion channels with ERS,
      although definitive genetic data do not yet exist to confirm pathogenicity.
      SUMMARY: ERS patients are rare and have a high risk of recurrent cardiac events.
      ICD implantation and possibly quinidine are the recommended treatments in this
      group. Opposingly, asymptomatic individuals with early repolarization are very
      common and, as a group, have a good prognosis. Sudden death preventive measures
      in these asymptomatic patients are limited to rare and unique cases.

PMID- 25389653
TI  - Cardiac intensive care for the neonate and child after cardiac surgery.
AB  - PURPOSE OF REVIEW: The focus of postoperative care in the pediatric patient with
      congenital heart disease has become a reduction in length of stay and morbidity.
      This review will discuss strategies to achieve this goal and recent studies to
      support current practices. RECENT FINDINGS: Most agree that prolongation of the
      length of stay following a cardiac surgery contributes to morbidity.
      Postoperative feeding difficulty, hyperglycemia, acute kidney injury, fluid
      overload, and prolonged intubation contribute significantly to length of stay.
      SUMMARY: Postoperative care of the neonate and child following a cardiac surgery
      remains challenging with limited data to drive our practices. Patients remain at
      risk for significant morbidity, and future studies should focus on recognizing
      predictors of morbidity, prevention, and treatment.

PMID- 25389654
TI  - When should we prescribe high-dose folic acid to prevent congenital heart
      defects?
AB  - PURPOSE OF REVIEW: Provide a rationale for attempting prevention of congenital
      heart defects (CHDs). RECENT FINDINGS: Prevention of neural-tube defects can be
      achieved with preconceptional use of folic acid. Extrapolating results from
      animal studies to human pregnancy shows that folate deficiency as well as one
      time exposure to environmental factors in the first 2 to 3 weeks of human
      gestation can result in severe CHD. Considering that approximately 50% of
      pregnancies are unplanned, this period of pregnancy can be considered high risk
      for cardiac, as well as neural, birth defects, as the woman usually is not aware
      of her pregnancy and may not yet be taking precautionary actions to protect the
      developing embryo. In mammals, folate supplementation prevents CHD induced by
      alcohol, by lithium, or by elevation of the metabolite homocysteine. Optimal
      protection of cardiogenesis was observed to occur with folate supplementation
      provided on the morning after conception and at higher doses than currently
      available in prenatal vitamin supplementation. Clinical studies show a similar
      pattern with high doses of folic acid required to prevent CHD. SUMMARY: Today,
      all patients with a family history of CHD should discuss the prenatal use of
      folate supplementation with their obstetricians prior to becoming pregnant.

PMID- 25389655
TI  - Atrial fibrillation and the athletic heart.
AB  - PURPOSE OF REVIEW: Endurance exercise, despite a plethora of proven health
      benefits, is increasingly recognized as a potential cause of lone atrial
      fibrillation. Moderate exercise reduces all-cause mortality and protects against
      developing atrial fibrillation. However, more intense exercise regimes confer
      modest incremental health benefits, induce cardiac remodelling and negate some of
      the cardiovascular benefits of exercise. The implications of endurance exercise
      and athletic heart are becoming increasingly relevant as the popularity of
      endurance exercise has increased 20-fold within a generation. RECENT FINDINGS: An
      apparent dose-response relationship exists between endurance exercise and left
      atrial dilatation. Repeated strenuous endurance exercise overloads atria,
      resulting in stretch-induced 'microtears', inflammation and endocardial scarring.
      Although these findings are observational in humans, similar mechanisms have
      recently been confirmed in animal models suggesting causation. SUMMARY:
      Currently, it is not known whether a ceiling for endurance exercise exists, and,
      if so, what factors determine the threshold of harm. Although preliminary
      research is promising, much work remains if we are to understand the mechanisms
      underpinning atrial fibrillation in athletes.

PMID- 25389656
TI  - Long-term progression and survival following Norwood Single Ventricle
      Reconstruction.
AB  - PURPOSE OF REVIEW: Much data exist concerning Norwood discharge mortality. Less
      is known about late survival. Examining the available data in light of the Single
      Ventricle Reconstruction trial is insightful as focus shifts toward long-term
      survival. RECENT FINDINGS: Data from 2000 to 2001 demonstrated approximately 40
      50% 10-year survival, 30-40% or less between 10 and 15 years. The shape of the
      curves was characteristic; the majority of deaths within the first year, followed
      by a late constant phase. Publications from 2001 to 2005 suggested that various
      combinations of technical and perioperative modifications allowed hospital
      discharge survivals as high as 90-94%. As results matured (2005-2010) a
      consistent message was that, although the shape of the newer curves was similar
      (highest hazard in the first 1 year), higher hospital survival shifted the later
      phase to yield better long-term survival (70-85% between 5 and 10 years). Some
      emphasized right ventricle-based shunts as a 'cause' of improving results. Since
      2010, the Single Ventricle Reconstruction trial has matured and has increasingly
      shifted opinion away from the right ventricle shunt as a 'cause' of improved
      results. The survival of the right ventricle shunt group is slightly higher at 3
      years, but the 1-year statistical significance has been lost and the two groups
      converge. As the Single Ventricle Reconstruction study was based on the
      interaction between randomized shunt and survival, the secondary and other
      endpoint analyses must be cautiously considered. SUMMARY: The current English
      language literature suggests a 60-80% 5-10 year survival expectation. The shape
      of the survival curve remains; the highest hazard remains the first year before a
      later, stable phase is reached. Rather than a 'magic bullet' theory surrounding
      one technique or practice, centers have differentially adopted various
      combinations to optimize Norwood survival. Optimizing interstage I survival is a
      challenge to further increase the percentage of patients reaching the late,
      stable phase.

PMID- 25389657
TI  - Reactivity of endohedral metallofullerene la2@c80 in nucleophilic and
      electrophilic attacks: vibronic coupling density approach.
AB  - The regioselectivities of La2@C80 in thermal nucleophilic and electrophilic
      attacks were theoretically investigated using vibronic coupling density (VCD)
      analysis. Nucleophilic and electrophilic cycloadditions to La2@C80 were
      experimentally reported to yield [6,6] and [6,5] adducts, respectively, as major
      products. VCD analysis provided a clear explanation for these experimental
      results. For nucleophilic reactions, it was found that the reactive [6,6] bonds
      did not have a large lowest unoccupied molecular orbital (LUMO) density and Fukui
      function but a large potential derivative with respect to a reaction mode. The
      VCD illustrates the origin of the interaction between the electronic and
      vibrational states. On the other hand, conventional reactivity indices such as
      frontier orbital density take only the electronic state into account. The result
      suggested that the stabilization due to vibronic couplings plays an important
      role in the regioselectivity of nucleophilic cycloadditions. The VCD with respect
      to the effective mode could provide a picture of the functional groups, which are
      the double bonds of ethylene moieties. VCD analysis with respect to hypothetical
      localized modes enabled the quantitative prediction of regioselectivities. 

PMID- 25389658
TI  - Stability and spectroscopy of single nitrogen dopants in graphene at elevated
      temperatures.
AB  - Single nitrogen (N) dopants in graphene are investigated using atomic-resolution
      scanning transmission electron microscopy (STEM) combined with electron energy
      loss spectroscopy (EELS). Using an in situ heating holder at 500  degrees C
      provided us with clean graphene surfaces, and we demonstrate that isolated N
      substitutional atoms remain localized and stable in the graphene lattice even
      during local sp(2) bond reconstruction. The high stability of isolated N dopants
      enabled us to acquire 2D EELS maps with simultaneous ADF-STEM images to map out
      the local bonding variations. We show that a substitutional N dopant causes
      changes in the EELS of the carbon (C) atoms it is directly bonded to. An upshift
      in the pi* peak of the C K-edge EELS of ~0.5 eV is resolved and supported by
      density functional theory simulations. 

PMID- 25389659
TI  - Efficacy evaluation of a multifunctional cosmetic formulation: the benefits of a
      combination of active antioxidant substances.
AB  - This study presents the association of active antioxidants substances in a
      multifunctional cosmetic formulation with established efficacy against signs of
      aging. A multifunctional cosmetic formulation containing an association of UV
      filters and antioxidant substances (liposoluble vitamins A, C and E, Ginkgo
      biloba and Phorphyra umbilicalis extracts) was evaluated. This formulation was
      submitted to a clinical efficacy study using biophysics techniques and skin
      images analysis (digital photography imaging systems, 20 MHz ultrasound, and
      reflectance confocal microscopy). The volunteers applied the formulation
      containing the UV filters and antioxidant substances during the day and the
      formulation with antioxidant substances and without the UV filters at night, for
      90 days. The formulation increased the hydration and protected the skin barrier
      function after a single application. At the long term assessment the formulation
      provided an improvement in skin barrier function and skin hydration to the deeper
      layers of the epidermis, leading to an improvement in skin appearance by reducing
      wrinkles and skin roughness. The multifunctional cosmetic formulation studied can
      be suggested to preventing signs of aging and improving skin conditions. In
      addition, this study presents the benefits of associating different active
      antioxidants substances in a single cosmetic formulation to prevent skin aging. 

PMID- 25389660
TI  - Curcumin reverse methicillin resistance in Staphylococcus aureus.
AB  - Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma
      longa L., was shown to possess superior potency to resensitize methicillin
      resistant Staphylococcus aureus (MRSA) to antibiotics. Previous studies have
      shown the synergistic activity of curcumin with beta-lactam and quinolone
      antibiotics. Further, to understand the anti-MRSA mechanism of curcumin, we
      investigated the potentiated effect of curcumin by its interaction in diverse
      conditions. The mechanism of anti-MRSA action of curcumin was analyzed by the
      viability assay in the presence of detergents, ATPase inhibitors and
      peptidoglycan (PGN) from S. aureus, and the PBP2a protein level was analyzed by
      western blotting. The morphological changes in the curcumin-treated MRSA strains
      were investigated by transmission electron microscopy (TEM). We analyzed
      increased susceptibility to MRSA isolates in the presence of curcumin. The
      optical densities at 600 nm (OD600) of the suspensions treated with the
      combinations of curcumin with triton X-100 and Tris were reduced to 63% and 59%,
      respectively, compared to curcumin without treatment. N,N'
      dicyclohexylcarbodiimide (DCCD) and sodium azide (NaN3) were reduced to 94% and
      55%, respectively. When peptidoglycan (PGN) from S. aureus was combined with
      curcumin, PGN (0-125 MUg/mL) gradually blocked the antibacterial activity of
      curcumin (125 MUg/mL); however, at a concentration of 125 ug/mL PGN, it did not
      completely block curcumin. Curcumin has a significant effect on the protein level
      of PBP2a. The TEM images of MRSA showed damage of the cell wall, disruption of
      the cytoplasmic contents, broken cell membrane and cell lysis after the treatment
      of curcumin. These data indicate a remarkable antibacterial effect of curcumin,
      with membrane permeability enhancers and ATPase inhibitors, and curcumin did not
      directly bind to PGN on the cell wall. Further, the antimicrobial action of
      curcumin involved in the PBP2a-mediated resistance mechanism was investigated. 

PMID- 25389661
TI  - A novel HPLC-assisted method for investigation of the Fe2+-chelating activity of
      flavonoids and plant extracts.
AB  - Flavonoids are a class of natural phenolic compounds that show antioxidant
      properties. Besides the known mechanisms of action of flavonoids
      (binding/inactivation of free radicals and other reactive oxygen species) that
      determine this effect, an important factor is their ability to bind transition
      metal ions. In this paper, we used a HPLC method with a prechromatographic
      reaction of a sample with Fe2+ ions (FeCA-HPLC) to characterize the Fe2+
      chelating properties of individual compounds, their mixtures, and plant extracts.
      Using two classes of flavonoids (flavones, flavonols) the ability of compounds to
      bind Fe2+ ions due to a number of structural features of the compounds was shown.
      If the compounds possessed Fe2+-chelating properties, the decrease in the area of
      the chromatographic peaks on the chromatogram was marked. By comparing the
      resulting chromatogram with that of the untreated sample, it was possible to
      estimate the value of the effect. Application of this method for the analysis of
      plant extracts representing a mixture of substances allows determination of the
      compounds that have the greatest influence on the Fe2+-chelating activity. 

PMID- 25389662
TI  - In vitro antioxidant and antiproliferative activities of methanolic plant part
      extracts of Theobroma cacao.
AB  - The aims of this study were to determine the antioxidant and antiproliferative
      activity of the following Theobroma cacao plant part methanolic extracts: leaf,
      bark, husk, fermented and unfermented shell, pith, root, and cherelle.
      Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH),
      thiobarbituric acid-reactive substances (TBARS), and Folin-Ciocalteu assays; the
      3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay was used to
      determine antiproliferative activity. The root extract had the highest
      antioxidant activity; its median effective dose (EC50) was 358.3+/-7.0 ug/mL and
      total phenolic content was 22.0+/-1.1 g GAE/100 g extract as compared to the
      other methanolic plant part extracts. Only the cherelle extract demonstrated
      10.4%+/-1.1% inhibition activity in the lipid peroxidation assay. The MTT assay
      revealed that the leaf extract had the highest antiproliferative activity against
      MCF-7 cells [median inhibitory concentration (IC50)=41.4+/-3.3 ug/mL]. Given the
      overall high IC50 for the normal liver cell line WRL-68, this study indicates
      that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but
      not in normal cells. Planned future investigations will involve the purification,
      identification, determination of the mechanisms of action, and molecular assay of
      T. cacao plant extracts.

PMID- 25389663
TI  - Chemical compositions, chromatographic fingerprints and antioxidant activities of
      Andrographis Herba.
AB  - This paper describes the development of an HPLC-UV-MS method for quantitative
      determination of andrographolide and dehydroandrographolide in Andrographis Herba
      and establishment of its chromatographic fingerprint. The method was validated
      for linearity, limit of detection and quantification, inter- and intra-day
      precisions, repeatability, stability and recovery. All the validation results of
      quantitative determination and fingerprinting methods were satisfactory. The
      developed method was then applied to assay the contents of andrographolide and
      dehydroandrographolide and to acquire the fingerprints of all the collected
      Andrographis Herba samples. Furthermore, similarity analysis and principal
      component analysis were used to reveal the similarities and differences between
      the samples on the basis of the characteristic peaks. More importantly, the DPPH
      free radical-scavenging and ferric reducing capacities of the Andrographis Herba
      samples were assayed. By bivariate correlation analysis, we found that six
      compounds are positively correlated to DPPH free radical scavenging and ferric
      reducing capacities, and four compounds are negatively correlated to DPPH free
      radical scavenging and ferric reducing capacities. 

PMID- 25389664
TI  - Cytotoxic mechanism of cytolethal distending toxin in nontyphoidal Salmonella
      serovar (Salmonella Javiana) during macrophage infection.
AB  - Cytolethal distending toxin B (cdtB) is a conserved virulence factor in
      Salmonella enterica serovar Typhi. Here we report the presence and functionality
      of cdtB in some nontyphoidal Salmonella (NTS) serovars, including Salmonella
      Javiana (cdtB+wt S. Javiana), isolated from imported food. To understand the role
      of cdtB in NTS serovars, a deletion mutant (cdtB(-)DeltaS. Javiana) was
      constructed. Macrophages were infected with cdtB+wt S. Javiana (wild type), cdtB(
      )Delta S. Javiana (mutant), and cdtB-negative NTS serovar (S. Typhimurium).
      Cytotoxic activity and transcription level of genes involved in cell death
      (apoptosis, autophagy, and necrosis) were assessed in infected macrophages. The
      cdtB+wt S. Javiana caused cellular distension as well as high degree of
      vacuolization and presence of the autophagosome marker LC3 in infected
      macrophages as compared with cdtB(-)DeltaS. Javiana. The mRNA expression of genes
      involved in the induction of autophagy in response to toxin (Esr1 and Pik3C3) and
      coregulators of autophagy and apoptosis (Bax and Cyld) were significantly
      upregulated in cdtB(+)wt S. Javiana-infected macrophages. As autophagy destroys
      internalized pathogens in addition to the infected cell, it may reduce the spread
      of infection. 

PMID- 25389665
TI  - Microplastics in four estuarine rivers in the Chesapeake Bay, U.S.A.
AB  - Once believed to degrade into simple compounds, increasing evidence suggests
      plastics entering the environment are mechanically, photochemically, and/or
      biologically degraded to the extent that they become imperceptible to the naked
      eye yet are not significantly reduced in total mass. Thus, more and smaller
      plastics particles, termed microplastics, reside in the environment and are now a
      contaminant category of concern. The current study tested the hypotheses that
      microplastics concentration would be higher in proximity to urban sources, and
      vary temporally in response to weather phenomena such as storm events. Triplicate
      surface water samples were collected approximately monthly between July and
      December 2011 from four estuarine tributaries within the Chesapeake Bay, U.S.A.
      using a manta net to capture appropriately sized microplastics (operationally
      defined as 0.3-5.0 mm). Selected sites have watersheds with broadly divergent
      land use characteristics (e.g., proportion urban/suburban, agricultural and/or
      forested) and wide ranging population densities. Microplastics were found in all
      but one of 60 samples, with concentrations ranging over 3 orders of magnitude
      (<1.0 to >560 g/km(2)). Concentrations demonstrated statistically significant
      positive correlations with population density and proportion of urban/suburban
      development within watersheds. The greatest microplastics concentrations also
      occurred at three of four sites shortly after major rain events. 

PMID- 25389666
TI  - Treatment of benign prostatic hyperplasia by occlusion of the impaired urogenital
      venous system - first experience.
AB  - PURPOSE: To effect regression of benign prostatic hyperplasia (BPH), Gat et al.
      (Andrologia 2008) proposed to occlude incompetent spermatic veins to reduce
      increased hydrostatic pressure on the prostatic venous plexus and prevent reflux
      with androgen rich blood from the testicles. Our aim was to implement this
      treatment strategy in clinical practice and to report about first results.
      METHODS: Embolization of the spermatic veins was performed in 30 patients with
      BPH. In 16 patients, we obtained follow-up data from at least 6 months. The
      sonographic transabdominal prostatic volume, prostate-specific antigen (PSA) and
      peripheral total testosterone levels were determined before and 6 months after
      the intervention. Subjective symptomatology was assessed using standardized
      questionnaires (International Prostate Symptom Score [IPSS] and Quality of Life
      score [QoL]) before and 6 months after the procedure. RESULTS: The age of all
      treated patients was 46 - 77 years. The age of the 16 patients who received
      follow-up was 51 - 77 years. IPSS (median 18 [IQR 20.75 - 14.50] vs. 9 [IQR 11.00
      - 7.25], p < 0.0001) and QoL score (4 [IQR 5 - 3] vs. 2 [IQR 3 - 1], p < 0.001)
      were significantly decreased 6 months after the intervention. The subjective
      improvement of symptoms did not correspond with prostatic volumes, which did not
      change significantly (54.31 +/- 30.90 vs. 50.50 +/- 29.26 ml, p = n. s.). 4/16
      patients had a measurable post-void urine volume, which decreased in two patients
      6 months after the procedure, remained unchanged in one patient, and was no
      longer detectable in one patient. 4 of the 11 had a sonographically detectable
      varicocele before the intervention, and one patient had a trabeculated bladder.
      Both the peripheral total testosterone levels (4.55 +/- 1.27 vs. 3.93 +/- 1.00
      ng/ml; p = n. s.) and PSA levels (3.74 +/- 2.83 vs. 4.06 +/- 3.34 ng/ml; p = n.
      s.) showed no significant differences. CONCLUSION: Interventional occlusion of
      the spermatic veins in patients with BPH is a feasible outpatient procedure with
      a low complication rate. Intermediate results are satisfactory. Mid- and long
      term results and pathophysiologic mechanisms need to be further elucidated.

PMID- 25389667
TI  - Magnetic resonance imaging of the sacroiliac joints in patients with suspected
      spondyloarthritis - comparison of turbo spin-echo and gradient-echo sequences for
      the detection of structural alterations.
AB  - PURPOSE: Magnetic resonance imaging (MRI) is the method of choice for the
      evaluation of spondyloarthritis (SpA). According to the guidelines of the
      Assessment of Spondyloarthritis International Society (ASAS) and Outcome Measures
      in Rheumatology (OMERACT), MRI findings in SpA of the spine and the sacroiliac
      joints (SIJ) are classified as inflammatory and structural alterations. Modern
      gradient-echo sequences (GRE) are recommended for optimized detection of
      structural alterations of the SIJ. We assess the benefit of GRE in the detection
      of structural alterations of the SIJ in comparison to conventional turbo spin
      echo sequences (TSE). MATERIAL AND METHODS: Retrospective study of 114 patients
      who received MRI of the SIJ for the evaluation of SpA. Structural alterations of
      the SIJ were assessed by two blinded readers separately for T1 TSE and T2* GRE.
      The findings were classified according to a previously published chronicity score
      separately for both sides and sequences. Interobserver reliability was calculated
      with Cohen's Kappa, and the significance of findings was assessed with the
      Wilcoxon test. P-values < 0.05 were required for statistical significance.
      RESULTS: 68 of 114 (60 %) patients showed SpA-typical findings of the SIJ. The
      average chronicity score for GRE (score 3.3) was significantly higher than for
      TSE (score 2.6), p = 0.001. The Kappa-values for the interobserver reliability
      were 0.86 - 0.90 without any statistically significant differences between both
      sides and sequences. CONCLUSION: Both T1 TSE and T2* GRE showed a high
      interobserver reliability in the detection of structural alterations in patients
      with SpA. However, T2* GRE detected significantly more structural alterations
      than T1 TSE and should be an integral part of a modern MRI protocol for the
      diagnostic workup of patients with suspected SpA.

PMID- 25389668
TI  - Features and limitations of mobile tablet devices for viewing radiological
      images.
AB  - PURPOSE: Mobile radiological image display systems are becoming increasingly
      common, necessitating a comparison of the features of these systems, specifically
      the operating system employed, connection to stationary PACS, data security and
      rang of image display and image analysis functions. MATERIAL AND METHODS: In the
      fall of 2013, a total of 17 PACS suppliers were surveyed regarding the technical
      features of 18 mobile radiological image display systems using a standardized
      questionnaire. The study also examined to what extent the technical
      specifications of the mobile image display systems satisfy the provisions of the
      Germany Medical Devices Act as well as the provisions of the German X-ray
      ordinance (RoV). RESULTS: There are clear differences in terms of how the mobile
      systems connected to the stationary PACS. Web-based solutions allow the mobile
      image display systems to function independently of their operating systems. The
      examined systems differed very little in terms of image display and image
      analysis functions. CONCLUSION: Mobile image display systems complement
      stationary PACS and can be used to view images. The impacts of the new quality
      assurance guidelines (QS-RL) as well as the upcoming new standard DIN 6868 - 157
      on the acceptance testing of mobile image display units for the purpose of image
      evaluation are discussed.

PMID- 25389669
TI  - Comparison of methods for acceptance and constancy testing in dental cone-beam
      computed tomography.
AB  - PURPOSE: The aim of this work was to implement, validate, and compare two
      procedures for routine image quality (IQ) assurance in dental cone-beam computed
      tomography (CBCT): 1. the German standard DIN 6868 - 161 introduced in 2013 and
      2. the established standard IEC 61,223 - 3-5 for clinical CT x-ray equipment
      referenced as "DIN" and "IEC" below. MATERIALS AND METHODS: The approximated in
      plane modulation transfer function (MTF), the contrast-to-noise indicator (CNI),
      and the uniformity indicator (UI*) were determined in accordance with DIN. Image
      noise, the uniformity index (UI), the contrast-to-noise ratio (CNR), and the 3 D
      MTF were measured according to IEC 61,223 - 3-5 using a previously proposed
      quality assurance (QA) framework. For this, a modular phantom was used. All
      experiments were performed on a clinical dental CBCT unit. The severity of image
      artefacts was measured at different z-positions. A dedicated computer program was
      implemented to allow for automated QA procedure. RESULTS: The position and
      orientation of the phantoms were detected automatically in all of the
      measurements providing a reproducible placement of the evaluation regions and
      volumes. 50 % and 10 % in-plane MTF values of the approximated and the exact MTF
      calculation procedure were in agreement to within 5 %. With increasing axial
      distance from the isocentre, UI* and CNI dropped by 30 % and 19 %, respectively.
      Conventional IQ parameters showed higher sensitivity to image artefacts; i. e.,
      UI and CNR were reduced by about 197 % and 37 %. CONCLUSION: The implemented
      automated QA routines are compatible with both the DIN and the IEC approach and
      offer reliable and quantitative tracking of imaging performance in dental CBCT
      for clinical practice. However, there is no equivalence between the DIN and the
      IEC metrics. In addition, direct measurements of physical IQ parameters such as
      image contrast and noise, uniformity, and axial resolution are not supported by
      the new concept according to DIN. KEY POINTS: The new DIN 6868 - 161 is not
      equivalent to the established IEC 61 223 - 3-5. Noise, uniformity, and contrast
      are well-suited to assess image artefacts. The implemented automated quality
      assurance program fits clinical routine.

PMID- 25389670
TI  - Epstein-barr infection of the retina: case report and review of the literature.
AB  - PURPOSE: The purpose of this study is to describe a presumed case of Epstein-Barr
      virus (EBV) infection of the retina in a 65-year-old female with sudden bilateral
      vision loss. METHODS: Diagnostic vitreous biopsy of the left eye was performed to
      test for EBV and other known infectious causes of retinitis and evaluate vitreous
      cells. RESULTS: Serologic EBV testing was positive. Vitreous polymerase chain
      reaction viral DNA testing was positive for EBV, but negative for herpes-simplex
      virus, varicella-zoster virus, cytomegalovirus, and toxoplasma gondii.
      Histopathologic analysis of vitreous cells revealed atypical lymphocytes.
      CONCLUSIONS: Epstein-Barr virus may be a cause of retinal disease. Awareness of
      this severe ocular complication may enable prompt diagnosis and treatment of
      future cases, and promote greater investigation into its disease prevalence.

PMID- 25389671
TI  - Subretinal abscess after strabismus surgery: case report and literature review.
AB  - PURPOSE: The purpose of this study is to describe the first reported case of a
      subretinal abscess after strabismus surgery and the successful treatment with
      vitrectomy, intravitreal antibiotics, and cryotherapy. METHODS: This is a
      retrospective case report and literature review. RESULTS: A 4-year-old boy
      underwent uncomplicated bilateral medial rectus muscle recession. Within 9 days
      after surgery, he developed unilateral endophthalmitis with a subretinal abscess
      at the approximate location of the medial rectus muscle insertion. The rectus
      muscle-scleral suture was removed, and transscleral cryotherapy was applied to
      the abscess site. Vitrectomy with injection of intravitreal antibiotics was
      performed. A bacterial culture of the removed suture was positive for
      Staphylococcus aureus and sensitive to his antibiotics. By 1 month, the abscess
      and vitritis had resolved completely. CONCLUSION: This is the first reported case
      of endophthalmitis with a subretinal abscess occurring after strabismus surgery.
      In general, endophthalmitis after strabismus surgery has a poor visual prognosis.
      Early diagnosis and intervention with intravitreal antibiotics and possible
      vitrectomy may be advantageous for patients with a subretinal abscess.

PMID- 25389672
TI  - Endogenous mycotic endophthalmitis in an immunocompetent postpartum patient.
AB  - PURPOSE: The purpose of this study was to report endogenous mycotic
      endophthalmitis in an immunocompetent postpartum patient who has undergone
      perineotomy in childbirth. METHODS: A 29-year-old immunocompetent postpartum
      woman had floaters in the left eye 2 weeks after childbirth. She denied ocular
      trauma, previous intraocular surgery, or intravenous drug use. The best-corrected
      visual acuity was 20/100 in the left eye. Anterior chamber cells, keratic
      precipitates, vitreous cells, and retinal infiltration were found. Endogenous
      endophthalmitis was highly suspected. The survey for infectious source was
      negative, but the culture of aqueous humor showed the presence of Cladosporium
      species. Pars plana vitrectomy and intravitreal 1 -MUg fluconazole injection were
      performed. The culture of the vitreous disclosed Candida albicans. Intravitreal
      injections with 5 MUg amphotericin-B and 0.1 mg voriconazole were given
      subsequently. Intravenous voriconazole 200 mg twice daily was administered for 2
      weeks and was shifted to the oral form for 4 more weeks. RESULTS: A residual
      retinal exudate resolved during follow-up. The best-corrected visual acuity was
      20/25 in the left eye 10 months later. CONCLUSION: This is the first case that
      illustrates the occurrence of endogenous mycotic endophthalmitis culture proved
      by Candida and Cladosporium in an immunocompetent patient. Early detection and
      appropriate treatment preserved vision.

PMID- 25389673
TI  - Culture-positive endophthalmitis 6 hours after intravitreal antibiotics.
AB  - PURPOSE: The purpose of this study was to report culture-positive endophthalmitis
      after intravitreal antibiotic injection and initial culture-negative tap.
      METHODS: This is an interventional case report of an 84-year-old woman who
      underwent vitrectomy and intravitreal antibiotic injection. The main outcome
      measures include resolution of infection, inflammation, and visual acuity
      improvement. RESULTS: Endophthalmitis after intravitreal pegaptanib injection was
      treated initially with a vitreous and aqueous tap and intravitreal antibiotic
      injection at a satellite clinic, because the patient was seen 5 hours from the
      nearest retina surgical facility. She subsequently underwent vitrectomy and
      intravitreal antibiotic injection. The initial culture results were negative and
      only the second culture was positive for Staphylococcus aureus. One year later,
      visual acuity was 20/30 after cataract extraction with intraocular lens
      implantation. CONCLUSION: When a suspected endophthalmitis case is seen many
      hours from a retina surgical facility, it may be best to perform tap and
      injection of intravitreal antibiotics although vitrectomy surgery may still be
      required but will be delayed.

PMID- 25389674
TI  - Long-term observation of exposed scleral exoplant without topical antibiotic
      prophylaxis.
AB  - PURPOSE: The purpose of this study was to describe a case of long-term
      observation without topical antibiotic prophylaxis for asymptomatic scleral
      exoplant exposure. METHODS: The medical records of a patient with long-term
      observation for asymptomatic scleral exoplant exposure were reviewed. RESULTS: No
      complications or clinical changes were noted throughout a 36-month course of
      observation for exoplant exposurei. CONCLUSION: Simple observation of
      asymptomatic scleral exoplant exposure is an alternative to observation with
      topical antibiotic prophylaxis if exoplant removal is deferred.

PMID- 25389675
TI  - Metastatic liposarcoma masquerading as an inflammatory granuloma.
AB  - PURPOSE: The purpose of this study was to report a case of retroperitoneal
      liposarcoma metastatic to the choroid. METHODS: A case report is presented of a
      67-year-old woman who presented with decreased vision from an extramacular lesion
      resembling an inflammatory granuloma in her left eye. The lesion showed rapid
      growth and was associated with extensive fibrovascular proliferation. RESULTS:
      Diagnostic vitrectomy showed malignant cells in the vitreous. Histopathologic
      evaluation of the enucleation specimen showed metastatic, dedifferentiated
      liposarcoma to the choroid with retinal penetration and vitreous invasion.
      CONCLUSION: Metastatic sarcoma to the choroid is very rare. In this case, the
      tumor was quite aggressive and penetrated through the retina, ultimately leading
      to enucleation.

PMID- 25389676
TI  - Retinoblastoma in a 48-year-old woman.
AB  - PURPOSE: The purpose of this study was to describe an unusual presentation of
      retinoblastoma in an adult. METHODS: Retrospective case report. RESULTS: A 48
      year-old woman with floaters was found to have an amelanotic intraocular mass
      with localized vitreous seeds in the superior fundus. Metastatic workup was
      negative. Cytologic examination of the vitrectomy specimen showed a malignant
      neoplasm with neuroendocrine differentiation, suspicious for carcinoid tumor. The
      patient later was found to have a lung lesion presumed to be a carcinoid tumor.
      She was treated with external beam radiation to the eye, but 1 year later, a new
      retinal tumor was discovered inferiorly requiring plaque radiotherapy. Soon
      thereafter, she developed massive intraocular recurrence. The eye was enucleated.
      Histopathology revealed small round blue cells with round hyperchromatic nuclei.
      Rosettes were also present within the tumor consistent with retinoblastoma.
      CONCLUSION: Late-onset retinoblastoma can occur in adults, and the diagnosis can
      be challenging.

PMID- 25389677
TI  - Neovascular glaucoma as the presenting sign of metastatic small cell lung
      carcinoma.
AB  - PURPOSE: The purpose of this study is to describe a case of metastatic lung
      cancer presenting with neovascular glaucoma. METHODS: This was a retrospective
      chart review describing one case. RESULTS: A previously healthy 36-year-old man
      presented with light perception vision and painful neovascular glaucoma.
      Examination and ultrasound showed a complete retinal detachment overlying a dome
      shaped choroidal mass. After enucleation, histopathology showed findings
      consistent with small cell lung carcinoma metastasis. Oncologic evaluation showed
      a necrotic lung carcinoma with extensive bony metastases. CONCLUSION: Metastatic
      carcinoma to the eye can manifest with features of neovascular glaucoma.

PMID- 25389678
TI  - Choroidal and optic disk metastases of a laryngeal carcinoma.
AB  - PURPOSE: To report a case of laryngeal squamous carcinoma metastatic to the eye
      affecting the choroid and optic nerve. METHODS: A 58-year-old man complained of
      sudden decrease of visual acuity in his left eye on admission to the emergency
      room. One year previously, he had undergone a surgical removal of laryngeal
      carcinoma. Funduscopic examination detected a choroidal mass in the macular area.
      RESULTS: After 10 days, the patient complained of pain and a diminished visual
      acuity and presented an exudative retinal detachment and optic nerve
      infiltration. CONCLUSION: Metastatic tumors are the most common intraocular
      malignancies, and the choroid is by far the most frequent location for the
      intraocular metastases. Metastases from a laryngeal carcinoma are quite unusual.
      Lesions affecting both choroid and optic nerve are extremely rare.

PMID- 25389679
TI  - Medulloepithelioma: invasive versus noninvasive diagnostic methods and their
      impacts on outcome.
AB  - PURPOSE: The purpose of this study was to report a case of a 34-month-old patient
      who presented with leukoria and underwent a vitrectomy and vitreous biopsy at an
      outside hospital followed by definitive enucleation for a nonteratoid
      medulloepithelioma and to review the literature regarding metastatic rates for
      this tumor after intraocular surgery. METHODS: The authors reviewed the clinical,
      histopathologic, and neuroimaging records in the unusual case of a child with
      medulloepithelioma who had previously undergone pars plana vitrectomy and
      vitreous biopsy. An in-depth literature search was performed for patients with
      medulloepithelioma with prior biopsy or surgery. RESULTS: Clinical examination
      showed a subluxed cataractous lens and neovascular glaucoma. Ultrasonography
      showed a large, cystic lesion with high reflectivity. Enucleation was performed,
      and histopathologic analysis showed a diffuse nonteratoid medulloepithelioma.
      CONCLUSION: Metastasis in medulloepithelioma is very rare. A systematic review of
      cases of patients with medulloepithelioma undergoing invasive intervention
      indicated that some patients subsequently developed metastases. Such procedures
      should be avoided to prevent orbital seeding or creating tracts for tumor
      migration and ultimate extraocular relapse.

PMID- 25389680
TI  - Aggressive amelanotic choroidal melanoma with extrascleral extension after
      brachytherapy.
AB  - PURPOSE: The purpose of this study was to report a case of amelanotic choroidal
      melanoma, previously treated with brachytherapy, subsequently exhibiting local
      extension through pars plana vitrectomy sites. METHOD: The authors present a
      retrospective interventional case report from a clinical practice. RESULTS: An
      amelanotic choroidal melanoma, previously responsive to brachytherapy, underwent
      two pars plana vitrectomies for nonclearing vitreous hemorrhage with double
      freeze cryotherapy to sclerotomy sites. Recurrent melanoma extended through the
      sclerotomies presenting as subconjunctival nodules requiring exenteration.
      CONCLUSION: Vitrectomy sclerotomy sites may serve as a route of extrascleral
      extension in previous brachytherapy treatment-responsive choroidal melanomas.
      Caution should be exercised in performing vitrectomy for choroidal melanomas with
      subsequent vitreous hemorrhage.

PMID- 25389681
TI  - Intraocular metastasis of testicular natural killer T-cell lymphoma with diffuse
      retinal pigment epithelium changes.
AB  - PURPOSE: The purpose of this study was to report the first confirmed case of
      testicular natural killer T-cell lymphoma with bilateral intraocular metastasis.
      METHODS: The author presents a chart review of a patient with testicular natural
      killer T-cell lymphoma metastasis to both eyes. This patient was treated with
      systemic chemotherapy, radiation, and intravitreal injections of methotrexate.
      RESULTS: The author identified one case of a patient with the diagnosis of
      bilateral metastatic natural killer T-cell lymphoma with ocular involvement
      treated with intravitreal methotrexate. After treatment, the patient developed
      diffuse widespread retinal pigment epithelium alterations in giraffe-like
      patterns. CONCLUSION: This represents a clinical case of a patient with primary
      testicular natural killer T-cell lymphoma and ocular metastasis with
      posttreatment retinal changes resembling bilateral diffuse uveal melanocytic
      proliferation.

PMID- 25389682
TI  - Characterization of kjellin syndrome using spectral-domain optical coherence
      tomography and fundus autofluorescence.
AB  - PURPOSE: The purpose of this study was to describe the characteristic funduscopic
      appearance of Kjellin syndrome, to report unique spectral-domain optical
      coherence tomography (Carl Zeiss Meditec, Dublin, CA) and fundus autofluorescence
      findings, and to provide long-term follow-up observations about this patient.
      METHODS: A 43-year-old man presented for an ophthalmologic examination with a
      known diagnosis of hereditary spastic paraplegia and no visual complaints.
      RESULTS: Retinal flecks were present throughout the macula in both eyes of the
      patient. Fluorescein angiography showed flecks with central hypofluorescence and
      peripheral hyperfluorescence. Fundus autofluorescence showed
      hyperautofluorescence in the center of the visible flecks and a surrounding halo
      of hypoautofluorescence. An abnormal latticelike network of hyperautofluorescence
      was present in the nasal retina of both eyes. Spectral domain-optical coherence
      tomography showed hyperreflective material, accounting for the flecks located at
      the level of the retinal pigment epithelium. At the 6-year follow-up, this
      patient had not developed any subjective visual changes, and the appearance of
      his fundus remained relatively unchanged. CONCLUSION: The presence of
      hyperautofluorescent material outside the posterior pole in patients with Kjellin
      syndrome has not been previously reported and suggests that retinal pigment
      epithelium involvement in this condition is not limited to the macula. Spectral
      domain-optical coherence tomography of this patient showed that the accumulation
      of hyperreflective material accounting for the flecks was located at the level of
      the retinal pigment epithelium. The 6-year follow-up findings suggest that this
      condition is either stationary or slowly progressive.

PMID- 25389683
TI  - Off-axis nonmydriatic photography to evaluate the posterior pole through small
      pupils.
AB  - PURPOSE: The purpose of this study was to improve the clarity of retinal images
      photographed through small pupils. METHODS: Retinal photographs were taken with a
      Topcon TRC-NW100 digital nonmydriatic camera centered and decentered about the
      pupillary axis. Four hundred and twelve consecutive individuals (age, 8-95 years)
      were screened for eye disease with nonmydriatic retinal photography in the
      District 33N Lions Eyemobile during a 1-year period. RESULTS: Twenty-nine percent
      of the eyes photographed had pupillary diameters <4 mm and yielded or would have
      yielded poor-quality images of the posterior pole with standard, on-axis
      alignment. In 78% of these eyes with small pupils, photography with off-axis
      alignment produced images of sufficient clarity for clinical assessment of
      retinal appearance. CONCLUSION: Off-axis alignment increases the percentage of
      gradable images of the posterior pole in individuals with small pupils.

PMID- 25389684
TI  - Brachial plexus neuropathy secondary to postoperative prone positioning for
      macular hole surgery.
AB  - PURPOSE: To report a case of unilateral brachial plexus neuropathy after prone
      positioning for macular hole repair. METHODS: Case report. RESULTS: After 7 days
      of strict prone positioning post-macular hole surgery, a 60-year-old patient
      developed severe pain and weakness in the left arm. Neurologic examination,
      imaging, and electromyography showed that the patient developed a unilateral
      brachial plexus neuropathy. Her strength and pain quickly improved after
      hospitalization and treatment with intravenous solumedrol, pain control, and
      physiotherapy. Her best-corrected vision improved from 20/400 to 20/40, however,
      she was left with frozen shoulder syndrome. CONCLUSION: After macular hole
      surgery, prone positioning with persistent abduction of the shoulder such that
      the patient's hands rest above the head may put patients at risk for a brachial
      plexus neuropathy. However, this risk may be minimized by the use of positioning
      assistive devices, reducing the duration in the prone position, instituting
      frequent breaks, and warning patients to look for signs of neuropathy.

PMID- 25389685
TI  - Sutureless 25-gauge vitrectomy for retinal detachment repair in a patient with
      osteogenesis imperfecta.
AB  - PURPOSE: The purpose of this study was to report the successful repair of retinal
      detachment in a patient with osteogenesis imperfecta with sutureless 25-gauge
      vitrectomy. METHODS: This was a single case report. RESULTS: A patient with
      osteogenesis imperfecta and a retinal detachment was successfully repaired
      without complication using 25-gauge vitrectomy with a final visual acuity of
      20/20. CONCLUSION: In light of abnormal and thin sclera in patients with
      osteogenesis imperfecta, small-gauge sutureless vitrectomy should be considered
      for the repair of retinal detachment in this subset of patients.

PMID- 25389686
TI  - Retinal detachments involving the posterior pole in hallermann-streiff syndrome.
AB  - PURPOSE: To report a case of Hallermann-Streiff syndrome and bilateral retinal
      detachments involving the posterior pole. METHODS: Retrospective case report and
      literature review. RESULTS: A 2-year-old girl with Hallermann-Streiff syndrome
      was evaluated. Fundus examination showed bilateral exudative retinal detachments
      involving a significant portion of the posterior pole. The left eye showed
      several large, cyst-like areas of retinal detachment. The child was observed
      without treatment, and the subretinal fluid remained stable during the follow-up
      of 10 months. CONCLUSION: Bilateral retinal detachments can be seen in patients
      with Hallermann-Streiff syndrome. The etiology is likely to be multifactorial,
      and uveal effusion may contribute to the exudative fluid. Further evaluation is
      necessary to determine the visual prognosis and optimal management of patients
      with exudative retinal detachments associated with Hallermann-Streiff syndrome.

PMID- 25389687
TI  - Ischemic central retinal vein occlusion and neovascular glaucoma as a result of
      optic nerve head drusen.
AB  - PURPOSE: The purpose of this study was to report a case of ischemic central
      retinal vein occlusion (CRVO) caused by optic nerve head drusen. METHODS: Case
      report and review of the literature. RESULTS: A healthy 13-year-old boy was
      diagnosed with bilateral optic nerve head drusen. Two years later, he developed
      an ischemic CRVO and secondary neovascular glaucoma. A full medical workup was
      negative. Despite treatment, his vision eventually declined to no light
      perception from a funnel detachment. CONCLUSION: Nonischemic CRVO or venous
      stasis retinopathy is a well-known entity associated with optic nerve head
      drusen. The authors report a case of ischemic CRVO in a patient with no
      underlying risks for this other than the observed drusen. This report clearly
      shows that optic nerve drusen may not be entirely benign and that they can
      precipitate ischemic CRVO.

PMID- 25389688
TI  - Hypercoagulable state in a patient with a retinal vein occlusion.
AB  - PURPOSE: The purpose of this study was to report unusual findings from a
      hypercoagu-lability workup of a patient with a retinal vein occlusion and to
      suggest the importance of investigating hypercoagulability in patients with
      similar presentations. METHODS: This is a retrospective case report of a patient
      seen in the clinic during a several-month period. RESULTS: The laboratory
      evaluation of the patient showed decreased antithrombin III activity and a
      prothrombin mutation, and platelet evaluation was consistent with sticky platelet
      syndrome. CONCLUSION: It is important to take a detailed history and pursue the
      possibility of hypercoagulability as an etiology for retinal vein occlusion in
      patients outside the classic, younger age group. This can lead to prompt
      intervention and possible prevention of future thrombotic events.

PMID- 25389689
TI  - Anomalous retinal vasculature in a patient with a history of aortic coarctation.
AB  - PURPOSE: The purpose of this study was to report a case of anomalous retinal
      vasculature in a patient with a history of aortic coarctation. METHODS: This is a
      case report. RESULTS: We present the case of a 4-month-old male infant with a
      history of juxtaductal aortic coarctation diagnosed on prenatal ultrasound,
      repaired at 2 weeks of life, who was referred for possible retinal detachment of
      the right eye. Examination under anesthesia and fluorescein angiography showed
      persistent fetal vasculature and tractional retinal detachment of the right eye
      and anomalous retinal vasculature of the left eye. CONCLUSION: Although aortic
      coarctation has been associated with arteriole corkscrew tortuosity and
      serpentine pulsation of arterioles, it can also be associated with an anomalous
      retinal vascular pattern.

PMID- 25389690
TI  - Sturge-weber syndrome and cerebral vascular av malformation in an african
      american adolescent.
AB  - PURPOSE: The purpose of this study was to report the case of a 16-year-old black
      man who without ocular history or physician-recognized dermatologic signs was
      found to have Sturge-Weber syndrome. METHODS: Color flow Doppler ultrasound and
      cerebral vascular imaging showed a child with Sturge-Weber syndrome with a
      cerebral vascular AV malformation. RESULTS: Color flow Doppler ultrasound and
      cerebral vascular imaging showed a total retinal detachment, diffuse choroidal
      hemangioma, and cerebral vascular AV malformation consistent with the diagnosis
      of Sturge-Weber syndrome. CONCLUSION: This case shows that this child with
      typical ocular vascular findings of Sturge-Weber syndrome and a cerebral AV
      malformation did not show recognizable evidence of a port wine stain during
      several physician examinations because of the child's darkly pigmented skin
      color.

PMID- 25389691
TI  - Spontaneous resolution of macular schisis in goldmann favre syndrome.
AB  - PURPOSE: The purpose of this study is to report a case of spontaneous flattening
      of macular schisis in a patient affected by Goldmann Favre syndrome (GFS).
      METHODS: A case report. RESULTS: A young boy affected by GFS came for a follow-up
      visit 10 years after the diagnosis. Spontaneous flattening of macular schisis,
      posterior hyaloid detachment, and visual acuity improvement from 20/200 to 20/80
      were observed in the left eye. CONCLUSION: The observed spontaneous resolution of
      schisis in GFS, a rare inherited vitreoretinal dystrophy, suggests that an
      abnormality of the vitreoretinal interface could be the origin of macular schisis
      in this patient. This observation, reported for the first time to our knowledge,
      also leads to the hypothesis that the inconsistent presence of schisis in
      patients with GFS may not be a simple difference in phenotype but rather
      corresponds to different evolutional stages of the macula alterations in patients
      affected by GFS.

PMID- 25389692
TI  - Hyphema after intravitreal injection of ranibizumab or bevacizumab.
AB  - BACKGROUND: Exudative age-related macular degeneration is commonly treated with
      intravitreal injection of medications containing antibodies against vascular
      endothelial growth factors, including ranibizumab (Lucentis, Genentech, South San
      Francisco, CA) and bevacizumab (Avastin, Genentech). To the best of our
      knowledge, hyphema has not previously been reported as a complication of
      intravitreal injection of ranibizumab or bevacizumab. METHODS: Retrospective case
      series. RESULTS: Three patients developed hyphema after intravitreal injection of
      anti-vascular endothelial growth factor medications: one after ranibizumab and
      two after bevacizumab. Two patients were pseudophakic and taking warfarin in
      combination with low-dose aspirin, and one was phakic and not taking any
      coagulation-altering medications. A total of 26,184 intravitreal injections of
      ranibizumab or bevacizumab were given during the study period, for an estimated
      incidence of hyphema after intravitreal injection of approximately 1 in 10,000.
      CONCLUSION: The authors describe hyphema, either gross or microscopic, as a
      complication of intravitreal injection of anti-vascular endothelial growth factor
      medications. In all three patients, best-corrected vision returned to baseline
      after resolution of the hyphema and subsequent injections occurred without
      complication.

PMID- 25389694
TI  - Reply.

PMID- 25389693
TI  - Cocaine and choroidal infarction, revisiting the triangular sign of amalric.
AB  - PURPOSE: To describe a case of choroidal infarction as illustrated by the
      "triangular sign of Amalric" after cocaine inhalation. METHODS: Observational
      case report. RESULTS: A 52-year-old male presented with an acute loss of vision
      in his left eye immediately after cocaine inhalation. Color photography and
      fluorescein angiography revealed triangular areas of choroidal ischemia following
      the distribution of the posterior ciliary arteries. CONCLUSION: Cocaine-induced
      vasospasm, specifically of the distal short posterior ciliary arteries, may
      explain the triangular wedge-shaped choroidal infarcts in our patient. A thorough
      drug history may circumvent unnecessary and costly investigations in such cases.

PMID- 25389695
TI  - Correspondence.

PMID- 25389697
TI  - Matching the decay half-life with the biological half-life: ImmunoPET imaging
      with (44)Sc-labeled cetuximab Fab fragment.
AB  - Scandium-44 (t1/2 = 3.9 h) is a relatively new radioisotope of potential interest
      for use in clinical positron emission tomography (PET). Herein, we report, for
      the first time, the room-temperature radiolabeling of proteins with (44)Sc for in
      vivo PET imaging. For this purpose, the Fab fragment of Cetuximab, a monoclonal
      antibody that binds with high affinity to epidermal growth factor receptor
      (EGFR), was generated and conjugated with N-[(R)-2-amino-3-(para-isothiocyanato
      phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N",N"-pentaacetic acid
      (CHX-A"-DTPA). The high purity of Cetuximab-Fab was confirmed by SDS-PAGE and
      mass spectrometry. The potential of the bioconjugate for PET imaging of EGFR
      expression in human glioblastoma (U87MG) tumor-bearing mice was investigated
      after (44)Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of
      ~12% ID/g at 4 h postinjection) of (44)Sc-CHX-A"-DTPA-Cetuximab-Fab with
      excellent tumor-to-background ratio, which might allow for same day PET imaging
      in future clinical studies. Immunofluorescence staining was conducted to
      correlate tracer uptake in the tumor and normal tissues with EGFR expression.
      This successful strategy for immunoPET imaging of EGFR expression using (44)Sc
      CHX-A"-DTPA-Cetuximab-Fab can make clinically translatable advances to select the
      right population of patients for EGFR-targeted therapy and also to monitor the
      therapeutic efficacy of anti-EGFR treatments. 

PMID- 25389702
TI  - Identification of Clathrate Hydrates, Hexagonal Ice, Cubic Ice, and Liquid Water
      in Simulations: the CHILL+ Algorithm.
AB  - Clathrate hydrates and ice I are the most abundant crystals of water. The study
      of their nucleation, growth, and decomposition using molecular simulations
      requires an accurate and efficient algorithm that distinguishes water molecules
      that belong to each of these crystals and the liquid phase. Existing algorithms
      identify ice or clathrates, but not both. This poses a challenge for cases in
      which ice and hydrate coexist, such as in the synthesis of clathrates from ice
      and the formation of ice from clathrates during self-preservation of methane
      hydrates. Here we present an efficient algorithm for the identification of
      clathrate hydrates, hexagonal ice, cubic ice, and liquid water in molecular
      simulations. CHILL+ uses the number of staggered and eclipsed water-water bonds
      to identify water molecules in cubic ice, hexagonal ice, and clathrate hydrate.
      CHILL+ is an extension of CHILL (Moore et al. Phys. Chem. Chem. Phys. 2010, 12,
      4124-4134), which identifies hexagonal and cubic ice but not clathrates. In
      addition to the identification of hydrates, CHILL+ significantly improves the
      detection of hexagonal ice up to its melting point. We validate the use of CHILL+
      for the identification of stacking faults in ice and the nucleation and growth of
      clathrate hydrates. To our knowledge, this is the first algorithm that allows for
      the simultaneous identification of ice and clathrate hydrates, and it does so in
      a way that is competitive with respect to existing methods used to identify any
      of these crystals. 

PMID- 25389698
TI  - Ad libitum fluid consumption via self- or external administration.
AB  - CONTEXT: During team athletic events, athletic trainers commonly provide fluids
      with water bottles. When a limited number of water bottles exist, various
      techniques are used to deliver fluids. OBJECTIVE: To determine whether fluid
      delivered via water-bottle administration influenced fluid consumption and
      hydration status. DESIGN: Crossover study. SETTING: Outdoor field (22.2 degrees C
      +/- 3.5 degrees C). PATIENTS OR OTHER PARTICIPANTS: Nineteen participants (14
      men, 5 women, age = 30 +/- 10 years, height = 176 +/- 8 cm, mass = 72.5 +/- 10
      kg) were recruited from the university and local running clubs. INTERVENTION(S):
      The independent variable was fluid delivery with 3 levels: self-administration
      with mouth-to-bottle direct contact (SA-DC), self-administration with no contact
      between mouth and bottle (SA-NC), and external administration with no contact
      between the mouth and the bottle (EA-NC). Participants warmed up for 10 minutes
      before completing 5 exercise stations, after which an ad libitum fluid break was
      given, for a total of 6 breaks. MAIN OUTCOME MEASURE(S): We measured the fluid
      variables of total volume consumed, total number of squirts, and average volume
      per squirt. Hydration status via urine osmolality and body-mass loss, and
      perceptual variables for thirst and fullness were recorded. We calculated
      repeated-measures analyses of variance to assess hydration status, fluid
      variables, and perceptual measures to analyze conditions across time. RESULTS:
      The total volume consumed for EA-NC was lower than for SA-DC (P = .001) and SA-NC
      (P = .001). The total number of squirts for SA-DC was lower than for SA-NC (P =
      .009). The average volume per squirt for EA-NC was lower than for SA-DC (P =
      .020) and SA-NC (P = .009). Participants arrived (601.0 +/- 21.3 mOsm/L) and
      remained (622.3 +/- 38.3 mOsm/L) hydrated, with no difference between conditions
      (P = .544); however, the EA-NC condition lost more body mass than did the SA-DC
      condition (P = .001). There was no main effect for condition on thirst (P = .147)
      or fullness (P = .475). CONCLUSIONS: External administration of fluid decreased
      total volume consumed via a decreased average volume per squirt. The SA-DC method
      requires fewer squirts within a specific time frame. Fluid breaks every 15
      minutes resulted in maintenance of euhydration; however, loss of body mass was
      influenced by fluid administration. Athletic trainers should avoid external
      administration to promote positive hydration behaviors. When fluid is self
      administered, individual bottles may be the best clinical practice because more
      volume can be consumed per squirt.

PMID- 25389703
TI  - Segmentation and classification of capnograms: application in respiratory
      variability analysis.
AB  - Variability analysis of respiratory waveforms has been shown to provide key
      insights into respiratory physiology and has been used successfully to predict
      clinical outcomes. The current standard for quality assessment of the capnogram
      signal relies on a visual analysis performed by an expert in order to identify
      waveform artifacts. Automated processing of capnograms is desirable in order to
      extract clinically useful features over extended periods of time in a patient
      monitoring environment. However, the proper interpretation of capnogram derived
      features depends upon the quality of the underlying waveform. In addition, the
      comparison of capnogram datasets across studies requires a more practical
      approach than a visual analysis and selection of high-quality breath data. This
      paper describes a system that automatically extracts breath-by-breath features
      from capnograms and estimates the quality of individual breaths derived from
      them. Segmented capnogram breaths were presented to expert annotators, who
      labeled the individual physiological breaths into normal and multiple abnormal
      breath types. All abnormal breath types were aggregated into the abnormal class
      for the purpose of this manuscript, with respiratory variability analysis as the
      end-application. A database of 11,526 breaths from over 300 patients was created,
      comprising around 35% abnormal breaths. Several simple classifiers were trained
      through a stratified repeated ten-fold cross-validation and tested on an unseen
      portion of the labeled breath database, using a subset of 15 features derived
      from each breath curve. Decision Tree, K-Nearest Neighbors (KNN) and Naive Bayes
      classifiers were close in terms of performance (AUC of 90%, 89% and 88%
      respectively), while using 7, 4 and 5 breath features, respectively. When
      compared to airflow derived timings, the 95% confidence interval on the mean
      difference in interbreath intervals was +/- 0.18 s. This breath classification
      system provides a fast and robust pre-processing of continuous respiratory
      waveforms, thereby ensuring reliable variability analysis of breath-by-breath
      parameter time series.

PMID- 25389704
TI  - Identification of the Infection Route of a Fusarium Seed Pathogen into Nondormant
      Bromus tectorum Seeds.
AB  - The genus Fusarium has a wide host range and causes many different forms of plant
      disease. These include seed rot and seedling blight diseases of cultivated
      plants. The diseases caused by Fusarium on wild plants are less well-known. In
      this study, we examined disease development caused by Fusarium sp. n on
      nondormant seeds of the important rangeland weed Bromus tectorum as part of
      broader studies of the phenomenon of stand failure or "die-off" in this annual
      grass. We previously isolated an undescribed species in the F. tricinctum species
      complex from die-off soils and showed that it is pathogenic on seeds. It can
      cause high mortality of nondormant B. tectorum seeds, especially under conditions
      of water stress, but rarely attacks dormant seeds. In this study, we used
      scanning electron microscopy (SEM) to investigate the mode of attack used by this
      pathogen. Nondormant B. tectorum seeds (i.e., florets containing caryopses) were
      inoculated with isolate Skull C1 macroconidia. Seeds were then exposed to water
      stress conditions (-1.5 MPa) for 7 days and then transferred to free water. Time
      lapse SEM photographs of healthy versus infected seeds revealed that hyphae under
      water stress conditions grew toward and culminated their attack at the abscission
      layer of the floret attachment scar. A prominent infection cushion, apparent
      macroscopically as a white tuft of mycelium at the radicle end of the seed,
      developed within 48 h after inoculation. Seeds that lacked an infection cushion
      completed germination upon transfer to free water, whereas seeds with an
      infection cushion were almost always killed. In addition, hyphae on seeds that
      did not initiate germination lacked directional growth and did not develop the
      infection cushion. This strongly suggests that the fungal attack is triggered by
      seed exudates released through the floret attachment scar at the initiation of
      germination. Images of cross sections of infected seeds showed that the fungal
      hyphae first penetrated the caryposis wall, then entered the embryo, and later
      ramified throughout the endosperm, completely destroying the seed.

PMID- 25389707
TI  - Achieving knowledge translation in nursing care: the need for greater rigor in
      applying evidence to practice.

PMID- 25389708
TI  - Decreased toll-like receptor-4/myeloid differentiation factor 88 response leads
      to defective interleukin-1beta production in term low birth weight newborns.
AB  - BACKGROUND: Morbidity and mortality rates are very high in low birth weight (LBW)
      newborns because of their increased susceptibility to infections compared with
      normal birth weight (NBW) newborns. A case and control study was designed to
      identify the status of toll-like receptor-4 (TLR-4) signaling and maternally
      derived immunoglobulin-G (IgG) subclasses in term LBW newborns compared with NBW
      newborns. METHODS: To understand the basis of increased susceptibility to
      infections in LBW newborns, the levels of pro- and antiinflammatory cytokines
      interleukin-1beta (IL-1beta) and interleukin-10 (IL-10), respectively, released
      in response to lipopolysaccharide (LPS) stimulation of cord blood cells of LBW (n
      = 20) and NBW (n = 18) newborns, were quantified by enzyme-linked immunosorbent
      assay. Further, LPS-induced expression of TLR-4 and basal and LPS-induced
      expression of myeloid differentiation factor 88 (MyD88) were examined at mRNA
      levels in both groups. The levels of IgG subclasses in LBW (n = 20) and NBW (n =
      18) newborns were quantified by enzyme-linked immunosorbent assay to explore the
      role of maternally derived immunity in LBW newborns. RESULTS: LPS-mediated
      release of IL-1beta was significantly diminished in LBW newborns when compared
      with NBW newborns, whereas there was no significant difference in IL-10.
      Decreased production of IL-1beta in LBW newborns was correlated with reduced
      expression of TLR-4 and MyD88 mRNA. No significant differences were observed in
      the levels of all 4 IgG subclasses between LBW and NBW newborns. CONCLUSIONS:
      Decreased production of IL-1beta in LBW newborns was correlated with reduced
      expression of TLR-4 and MyD88 mRNA. This raises the possibility of increased
      susceptibility to infections in LBW when compared with the NBW newborns at term.
      Comparable levels of IgG subclasses in the 2 groups of newborns indicate that IgG
      is not a limiting factor in defense against infection in LBW newborns.

PMID- 25389709
TI  - Susceptibility to pediatric Helicobacter pylori infection correlates with the
      host responses of regulatory and effector T cells.
AB  - BACKGROUND: Tolerance to the early acquisition of Helicobacter pylori is
      suggested because of a biased ratio of regulatory to effector T cells in a mice
      model. This study investigated whether the CD4CD25 regulatory T (Treg) and
      CD4+CD25- effector T (Teff) cell responses after H. pylori exposure determine H.
      pylori susceptibility in children. METHODS: Treg and Teff cells from peripheral
      blood mononuclear cells (PBMCs) of H. pylori-infected and non-infected children
      were incubated with H. pylori protein. The cytokine levels and fraction of FOXP3+
      to T cells were measured. FOXP3 expression was assessed by Western blotting and
      immunohistochemistry of gastric biopsies from dyspeptic children. RESULTS: The
      fraction of FOXP3+ to CD4+CD25 high cells in PBMCs, FOXP3-positive staining and
      translation level in gastric tissues were higher in H. pylori-infected children
      than in controls (P < 0.05). The translation levels of TGF-beta1 in gastric
      tissues were higher in H. pylori-infected children than in controls (P < 0.05).
      After H. pylori challenge, H. pylori-infected children had a positive net-change
      in TGF-beta1 from Treg cells, and a negative net-change of IFN-gamma from Teff
      cells. Paradoxically, the non-infected controls had a negative net-change in TGF
      beta1 from Treg cells, and a positive net-change of IFN-gamma from Teff cells.
      CONCLUSIONS: The host response of Treg cells with increases in FOXP3 and TGF
      beta1 combined with a reduction in IFN-gamma by Teff cells may contribute to H.
      pylori susceptibility in children.

PMID- 25389710
TI  - Lactate dehydrogenase concentration in nasal wash fluid indicates severity of
      rhinovirus-induced wheezy bronchitis in preschool children.
AB  - The clinical course of rhinovirus (RV)-associated wheezing illnesses is difficult
      to predict. We measured lactate dehydrogenase concentrations, RV load, antiviral
      and proinflammatory cytokines in nasal washes obtained from 126 preschool
      children with RV wheezy bronchitis. lactate dehydrogenase values were inversely
      associated with subsequent need for oxygen therapy. lactate dehydrogenase may be
      a useful biomarker predicting disease severity in RV wheezy bronchitis. 

PMID- 25389711
TI  - Sample preparation composite and replicate strategy for assay of solid oral drug
      products.
AB  - In pharmaceutical analysis, the results of drug product assay testing are used to
      make decisions regarding the quality, efficacy, and stability of the drug
      product. In order to make sound risk-based decisions concerning drug product
      potency, an understanding of the uncertainty of the reportable assay value is
      required. Utilizing the most restrictive criteria in current regulatory
      documentation, a maximum variability attributed to method repeatability is
      defined for a drug product potency assay. A sampling strategy that reduces the
      repeatability component of the assay variability below this predefined maximum is
      demonstrated. The sampling strategy consists of determining the number of dosage
      units (k) to be prepared in a composite sample of which there may be a number of
      equivalent replicate (r) sample preparations. The variability, as measured by the
      standard error (SE), of a potency assay consists of several sources such as
      sample preparation and dosage unit variability. A sampling scheme that increases
      the number of sample preparations (r) and/or number of dosage units (k) per
      sample preparation will reduce the assay variability and thus decrease the
      uncertainty around decisions made concerning the potency of the drug product. A
      maximum allowable repeatability component of the standard error (SE) for the
      potency assay is derived using material in current regulatory documents. A table
      of solutions for the number of dosage units per sample preparation (r) and number
      of replicate sample preparations (k) is presented for any ratio of sample
      preparation and dosage unit variability. 

PMID- 25389712
TI  - Specialized surveillance for individuals at high risk for melanoma: a cost
      analysis of a high-risk clinic.
AB  - IMPORTANCE: Regular surveillance of individuals at high risk for cutaneous
      melanoma improves early detection and reduces unnecessary excisions; however, a
      cost analysis of this specialized service has not been undertaken. OBJECTIVE: To
      determine the mean cost per patient of surveillance in a high-risk clinic from
      the health service and societal perspectives. DESIGN, SETTING, AND PARTICIPANTS:
      We used a bottom-up microcosting method to measure resource use in a consecutive
      sample of 102 patients treated in a high-risk hospital-based clinic in Australia
      during a 12-month period. EXPOSURE: Surveillance and treatment of melanoma. MAIN
      OUTCOMES AND MEASURES: All surveillance and treatment procedures were identified
      through direct observation, review of medical records, and interviews with staff
      and were valued using scheduled fees from the Australian government. Societal
      costs included transportation and loss of productivity. RESULTS: The mean number
      of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95%
      CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per
      patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI,
      US $532-$665]); the cost discounted across 20 years was A $11,546 (95% CI, A
      $10,263-$12,829) (US $7839 [95% CI, US $6969-$8710]). The mean annual societal
      cost per patient (excluding health system costs) was A $972 (95% CI, A $899
      $1045) (US $660 [95% CI, US $611-$710]); the cost discounted across 20 years was
      A $12,721 (95% CI, A $12,554-$14,463) (US $8637 [95% CI, US $8523-$9820]).
      Diagnosis of melanoma or nonmelanoma skin cancer and frequent excisions for
      benign lesions in a relatively small number of patients was responsible for
      positively skewed health system costs. CONCLUSIONS AND RELEVANCE: Microcosting
      techniques provide an accurate cost estimate for the provision of a specialized
      service. The high societal cost reflects the time that patients are willing to
      invest to attend the high-risk clinic. This alternative model of care for a high
      risk population has relevance for decision making about health policy.

PMID- 25389713
TI  - Primary On-top Plasty for Treatment of Short-type Postaxial Polydactyly of the
      Foot.
AB  - BACKGROUND: Postaxial polydactyly of the foot is typically treated with medial or
      lateral toe ray resection. However, simple ray resection does not always give a
      natural postoperative appearance, especially for short-type polydactyly. The
      purpose of this article was to describe our primary operation with on-top plasty
      for lengthening of short-type postaxial polydactyly. METHODS: Four patients (mean
      age, 11.3 months) underwent this procedure. Ray transfer was performed at the
      proximal phalangeal level. Lateral distal and middle phalanges were resected and
      the medial ray was transferred on top of the remaining lateral proximal phalanx.
      Preoperative and postoperative toe lengths and complications were evaluated by
      comparison with the contralateral side on x-ray. RESULTS: All toes were
      lengthened by a mean of 115.1% from the tip of the distal phalanx to the bottom
      of the proximal phalanx relative to contralateral side. Appearances were very
      natural without valgus deformity and hypertrophic scar. And there was no
      remaining dysfunction in walking after a mean of 21.5 months follow-up.
      CONCLUSIONS: This on-top procedure is useful for improving toe lengthening and
      bone alignment correction with minimal functional disturbance.

PMID- 25389714
TI  - Plastic Surgery Mortality: An 11-Year, Single-Institution Experience.
AB  - BACKGROUND: Systematic reporting of mortality data is lacking in many surgical
      fields including plastic surgery. Current plastic surgery literature is largely
      limited to adverse events associated with specific procedures. Without mortality
      data, it is unclear how the recent growth of patient safety initiatives can
      rationally impact outcomes. METHODS: We evaluated 11 years of patient outcome
      data collected prospectively and updated monthly by our department. Paper records
      were entered into a Health Insurance Portability and Accountability Act-compliant
      digital database capable of prospectively maintaining future data. Data were
      reviewed for 5 surgical services in 4 different hospitals that comprise our
      department's activity. RESULTS: Between 2000 and 2011, a total of 60,834 cases
      were performed. In this time, a total of 829 (1.4%) negative outcome reports were
      identified. Of these, a total of 25 (0.04%) cases had an outcome of death (24) or
      brain death (1). Deaths were either directly or indirectly associated with
      cardiopulmonary causes, multisystem organ failure, sepsis, massive bleeding, CVA,
      saddle embolism, or unknown causes. CONCLUSIONS: This study is the largest
      reported series of cases performed by a single academic plastic surgery service
      to report overall mortality data.

PMID- 25389715
TI  - A Comparison of Dermal Autograft and Acellular Dermal Matrix in Tissue Expander
      Breast Reconstruction: Long-term Aesthetic Outcomes and Capsular Contracture.
AB  - BACKGROUND: The use of acellular dermal matrix (ADM) in tissue expander breast
      reconstruction has been touted to reduce capsular contracture rates and improve
      aesthetic outcomes. Autogenous dermal grafts have shown to be a safer and more
      cost-effective alternative to ADM. The purpose of this study was to compare the
      capsular contracture rates and long-term aesthetic outcomes of tissue expander
      breast reconstruction using dermal autografts with ADM-assisted reconstruction.
      METHODS: Patients undergoing tissue expander breast reconstruction with either
      ADM or dermal autografts were enrolled. Autografts were harvested from the lower
      abdomen. The capsular contracture rate was assessed via physical examination
      using the Baker scale. Standardized patient photographs were scored for aesthetic
      appearance on a 7-point Likert scale by blinded female observers. The ADM and
      autograft groups were compared using Student t test. Significance was defined as
      P < 0.05. RESULTS: Forty-eight patients were enrolled (76 breasts). The average
      follow-up time for the ADM group was 9.6 months and 9.9 months for the dermal
      autograft group. Twenty-seven patients received ADM, and 21 patients received
      dermal autograft. Capsular contracture scores were identical between the 2 groups
      (mean Baker grade = 1.15, P = 0.55). The average long-term aesthetic outcome
      score for dermal autograft-assisted breast reconstruction was 3.85, compared to
      3.79 for ADM-assisted reconstruction. This difference was not statistically
      significant (P = 0.87). CONCLUSIONS: In addition to an improved safety profile
      and lower cost, dermal autograft-assisted tissue expander breast reconstruction
      affords equivalent aesthetic results and capsular contracture rates, when
      compared to ADM.

PMID- 25389716
TI  - Efferent Lymphatic Vessel Anastomosis: Supermicrosurgical Efferent Lymphatic
      Vessel-to-Venous Anastomosis for the Prophylactic Treatment of Subclinical
      Lymphedema.
AB  - BACKGROUND: In lower extremity lymphedema secondary to pelvic cancer treatments,
      lymphedema develops despite that the inguinal lymph nodes (LNs) are preserved.
      Obstruction of the efferent lymphatic vessels of the inguinal LNs causes lower
      extremity lymphedema, and it is considered a radical treatment to bypass the
      efferent lymphatic vessel. METHODS: Efferent lymphatic vessel anastomosis,
      supermicrosurgical efferent lymphatic vessel-to-venous anastomosis, was performed
      on 14 legs with subclinical lymphedema [leg dermal backflow (LDB) stage I].
      Efferent lymphatic vessel anastomosis was performed under local anesthesia at the
      groin region, and an efferent lymphatic vessel of the inguinal LN is anastomosed
      to a recipient vein. Feasibility and postoperative results were evaluated.
      RESULTS: All 14 efferent lymphatic vessel anastomoses were successfully performed
      without perioperative complication. All legs could be free from lymphedematous
      symptoms without perioperative compression at postoperative 1 year. Postoperative
      LDB stage included LDB stage 0 (n = 8) and LDB stage I (n = 6), which was
      significantly downstaged compared with preoperative LDB stage (P < 0.001).
      CONCLUSIONS: Efferent lymphatic vessel anastomosis allowed lymph flow bypass
      after filtration by the superficial inguinal LN through a skin incision along the
      inguinal crease, and was effective to prevent development of symptomatic
      lymphedema in subclinical lymphedema cases.

PMID- 25389717
TI  - Diving-related visual loss in the setting of angioid streaks: report of two
      cases.
AB  - PURPOSE: The purpose of this study was to report diving-related visual loss in
      the setting of angioid streaks. METHODS: Observational case reports of two
      patients with angioid streaks suffering sudden visual loss immediately after
      diving. RESULTS: Two young adult male patients presented with visual loss after
      diving headfirst. Funduscopy revealed angioid streaks, peau d'orange, subretinal
      hemorrhages, and ruptures of Bruch membrane. Choroidal neovascularization
      developed during follow-up. Both patients had an otherwise uneventful personal
      and familial medical history. CONCLUSION: In patients with angioid streaks,
      diving headfirst can lead to subretinal hemorrhages and traumatic ruptures in
      Bruch membrane and increase the risk of maculopathy. Ophthalmologists should
      caution patients with angioid streaks against diving headfirst.

PMID- 25389718
TI  - Difluprednate ophthalmic emulsion 0.05% as adjunctive treatment to panretinal
      photocoagulation for proliferative diabetic retinopathy with clinically
      significant macular edema.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of topical
      difluprednate ophthalmic emulsion in controlling progressive diabetic macular
      edema after panretinal photocoagulation. METHODS: This was a case report of two
      patients with proliferative diabetic retinopathy combined with diabetic macular
      edema who underwent panretinal photocoagulation combined with use of a topical
      difluprednate ophthalmic emulsion. RESULTS: In the Case 1, retinal thickness was
      decreased 29% 1 month after the start of difluprednate treatment and best
      corrected visual acuity was improved 20/40 to 20/25. In Case 2, retinal thickness
      was decreased 43% after 1 month, and best-corrected visual acuity was improved
      20/100 to 20/60 after 3 months. During the follow-up period, elevation of
      intraocular pressure, ocular infection, and progression of cataract were not
      detected, though superficial punctuate keratitis was observed in one case.
      CONCLUSION: Topical difluprednate ophthalmic emulsion was one of the possible
      choices to treat progressive diabetic macular edema after panretinal
      photocoagulation. It is mandatory to evaluate the effects and safety in further
      studies including many cases.

PMID- 25389719
TI  - Lyme disease: resolution of a serous retinal detachment and chorioretinal folds
      after antibiotic therapy.
AB  - BACKGROUND: Ocular manifestations of Lyme disease are uncommon. There has not
      been a documented case of serous retinal detachment and chorioretinal folds
      because of Lyme disease that have resolved after only antibiotic treatment.
      METHODS (CASE REPORT): A 69-year-old white man with a history of recent tick
      bites presented with a gradual decrease in visual acuity in the left eye. Initial
      visual acuity was 3/200 in the left eye. Examination revealed an inferior,
      serous, macula-off retinal detachment. Chorioretinal folds were also noted. Lyme
      screening antibody test (enzyme-linked immunosorbent assay) was positive and a
      confirmatory Western blot was immunoglobulin M negative and immunoglobulin G
      positive. RESULTS: Oral amoxicillin (500 mg 3 times daily for 2 weeks) was given
      followed by intravenous ceftriaxone (2 g daily for 4 weeks). After two weeks of
      ceftriaxone, fundus examination and ultrasonography showed complete reattachment
      of the macula and periphery, and only mild residual chorioretinal folds remained
      on fluorescein angiogram. CONCLUSION: We suggest that Borrelia burgdorferi
      infection led to choroidal inflammation with secondary chorioretinal folds and a
      serous retinal detachment, which resolved with antibiotic therapy alone. This
      supports the suspicion of an intraocular infection, perhaps involving the
      choroid, as opposed to a secondary autoimmune reaction.

PMID- 25389720
TI  - New aspects of viral necrotizing retinitis in subacute sclerosing panencephalitis
      with spectral-domain optical coherence tomography.
AB  - PURPOSE: To report the clinical, angiographic, and tomographic features of an
      adult patient with bilateral occlusive vasculitis and necrotizing retinitis
      preceding the onset of subacute sclerosing panencephalitis by 3 years. METHODS:
      Observational case report. RESULTS: A 39-year-old white man presented with sudden
      onset of decreased vision in his left eye. The patient reported a history of
      right visual loss 3 years ago after an episode of retinal vasculitis of unknown
      origin. At presentation, left fundus examination showed sensory retinal
      detachment and retinal hemorrhages in the left macula. Fluorescein angiography
      revealed occlusive vasculitis. Two weeks later, several circumscribed lesions of
      necrotizing retinitis appeared in the macula and in the midperiphery after a
      centrifugal linear pattern from the optic nerve. Spectral-domain optical
      coherence tomography demonstrated focal areas of moth-eaten disorganization of
      the ganglion cell and nuclear layers with a spreading from the inner layers to
      the outer layers. CONCLUSION: This unusual case of adult-onset subacute
      sclerosing panencephalitis may help improve our knowledge regarding the mechanism
      of retinal involvement in this disease. Clinical and tomographic findings suggest
      a continuous transneuronal spread of the measles virus from ganglion cells to the
      photoreceptor cells.

PMID- 25389721
TI  - Retinal detachment because of macular hole and an additional break within the
      staphyloma.
AB  - PURPOSE: To report the finding of retinal detachment because of macular hole and
      an additional break within the posterior staphyloma. METHODS: A 63-year-old woman
      presented with progressive central scotoma of the right eye for 1-month duration.
      The fundus in the right eye showed retinal detachment that was localized within
      the posterior staphyloma and macular hole. An additional retinal break was
      observed within the staphyloma using ophthalmoscope, and optical coherence
      tomography confirmed that both the breaks were within the staphyloma. Macular
      buckling was scheduled because the two breaks were close enough to each other and
      the patient was unable to maintain a prone position. RESULTS: The retinal
      detachment was successfully reattached using macular buckling procedure.
      CONCLUSION: In the present case, optical coherence tomography proved to be very
      useful in helping to make the correct diagnosis of a full-thickness break before
      surgery.

PMID- 25389722
TI  - Ocular nocardiosis in a renal transplant patient: a warning of life-threatening
      underlying systemic disease.
AB  - PURPOSE: To describe a case of an immunosuppressed patient with history of renal
      transplant that presented with sudden unilateral loss of vision. METHODS: Case
      report. Review of medical records. RESULTS: A 49-year-old man with history of
      renal transplantation presenting with visual symptoms without initial systemic
      manifestations. Because of the rarity of ocular involvement, the patient's
      diagnosis of Nocardia asteroides endophthalmitis was delayed culminating in
      systemic involvement and necessitating enucleation of the eye. CONCLUSION:
      Nocardiosis is a serious life-threatening complication in immunosuppressed
      patients. Visual symptoms and endophthalmitis in this population should raise the
      suspicion of a possible serious systemic infection like nocardia.

PMID- 25389723
TI  - Vitreomacular adhesion associated with foveal-sparing preretinal hemorrhage.
AB  - PURPOSE: To report two cases of central macular sparing of subhyaloid hemorrhages
      secondary to vitreomacular adhesion documented by spectral-domain ocular
      coherence tomography findings. METHODS: Review of two patients with subhyaloid
      hemorrhage secondary to proliferative diabetic retinopathy and a macroaneurysm
      were performed. Treatment was not performed in either patient for management of
      the hemorrhage, but the patient with proliferative diabetic retinopathy was
      treated with panretinal photocoagulation for peripheral neovascularization.
      Foveal sparing of the hemorrhage was documented clinically and on spectral-domain
      ocular coherence tomography. RESULTS: In Case 1, the proliferative diabetic
      retinopathy was stabilized with 2 rounds of panretinal photocoagulation
      treatment, and the visual acuity improved to 20/20 in the affected left eye after
      8 months of observation. In Case 2, the visual acuity returned to baseline at
      20/60 after 4 months of observation. CONCLUSION: Macular involvement of
      subhyaloid hemorrhages may cause visual impairment, but vitreomacular adhesion
      may block the hemorrhage from obstructing the fovea.

PMID- 25389724
TI  - Vertical transmission of macular telangiectasia type 2.
AB  - PURPOSE: The purpose of this study was to report vertical transmission of macular
      telangiectasia type 2 and type 2 diabetes mellitus in 3 families. METHODS: In
      this retrospective interventional case series, the charts of patients with
      inherited macular telangiectasia type 2 were reviewed. A large spectrum of
      presentations of macular telangiectasia type 2 was observed and has been studied
      with different techniques including best-corrected visual acuity, microperimetry,
      confocal blue reflectance fundus autofluorescence, fluorescein angiography, and
      time domain and spectral domain optical coherence tomography. RESULTS: Vertical
      transmission of macular telangiectasia type 2 and associated type 2 diabetes
      mellitus is described in 3 families. Symptomatic as well as asymptomatic eyes
      with macular telangiectasia type 2 were identified. In 2 families, a mother and
      son experienced visual loss and were diagnosed with macular telangiectasia type
      2. All 4 patients had type 2 diabetes. Diabetic retinopathy was observed in one
      mother and her son. In the third family, the index patient was diagnosed macular
      telangiectasia type 2 after complaints of metamorphopsia. She and her family
      members had type 2 diabetes mellitus, and further screening of her family
      revealed familial macular telangiectasia type 2. None of the patients were
      treated for macular telangiectasia type 2. CONCLUSION: Macular telangiectasia
      type 2 may be more common than previously assumed, as vision can remain preserved
      and patients may go undiagnosed. Screening of family members is indicated, and
      detection of mild anomalies is possible using fundus autofluorescence and
      spectral domain optical coherence tomography.

PMID- 25389725
TI  - Postponed closure of a postoperative macular hole.
AB  - PURPOSE: The purpose of this study was to report an exceptional case of a
      postponed closure of a postoperative macular hole. METHODS: A 60-year-old woman
      received a diagnosis of idiopathic macular hole after she suffered decreased
      vision in her left eye for 3 weeks. She underwent a pars plana vitrectomy, fluid
      air exchange, and room air tamponade with face down positioning for 5 days,
      without internal limiting membrane peeling. Optical coherence tomography scans
      were performed at 3 days, 3 months, and 6 months after surgery. RESULTS: Macular
      hole did not achieve closure until 6 months after surgery. CONCLUSION: Postponed
      closure in a case of a postoperative macular hole is rare. This report shows that
      idiopathic macular hole, which does not close immediately after surgery, still
      has the possibility to achieve closure.

PMID- 25389726
TI  - Postoperative choroidal hemorrhage shows elevated concentration of tissue
      plasminogen activator.
AB  - PURPOSE: The purpose of this study was to report the levels of tissue plasminogen
      activator in liquefied suprachoroidal hemorrhage. METHODS: An interventional case
      report of a 61-year-old woman who underwent drainage sclerotomy for choroidal
      hemorrhage. RESULTS: A 61-year-old pseudophakic woman underwent pars plana
      vitrectomy and fluid-gas exchange for retinal detachment in her right eye and
      developed postoperative serous choroidal detachments with large hemorrhages.
      Drainage sclerotomy was performed 18 days after the initial development of
      suprachoroidal hemorrhage. Sample of the liquefied hemorrhage and serum sample
      collected during sclerotomy were tested for tissue plasminogen activator levels
      using the antibody tissue plasminogen activator-enzyme immunoassay test.
      Hemorrhage tissue plasminogen activator levels were three times the levels
      present in the serum. CONCLUSION: Tissue plasminogen activator may be involved in
      the process of suprachoroidal hemorrhage liquefaction.

PMID- 25389727
TI  - Transcleral posterior chamber paracentesis for angle closure glaucoma secondary
      to posterior chamber gas entrapment after intravitreal c3f8 injection in a phakic
      eye.
AB  - PURPOSE: The purpose of this study was to describe a new technique for treating a
      case of angle closure glaucoma secondary to posterior chamber (PC) gas entrapment
      after intravitreal C3F8 injection. METHODS: Retrospective case report. RESULTS: A
      26-year-old woman received intravitreal injection of 0.4 mL of C3F8 after
      segmental scleral buckling for retinal detachment of her phakic eye. Prone
      positioning was not maintained postoperatively, and severe eye pain developed
      within hours of surgery. Intraocular pressure increased to 50 mmHg, and PC was
      found to be filled with gas accompanying with 360 degrees  iridocorneal
      apposition and angle closure. Transcleral PC paracentesis was performed to
      evacuate the gas. Anterior chamber angle was reopened inferiorly, and intraocular
      pressure dropped to 13 mmHg immediately and remained normal. No evidence of lens
      or iris damage was noted. Postoperatively, the vision improved to 20/25 without
      major sequelae. CONCLUSION: Posterior chamber gas entrapment with anterior
      chamber collapse is a rare complication of intravitreal gas injection in phakic
      eyes. Transcleral PC paracentesis is a safe way to treat angle closure glaucoma
      secondary to PC gas entrapment.

PMID- 25389728
TI  - Reversible mental status change and renal dysfunction associated with the use of
      high-dose oral valaciclovir therapy for acute retinal necrosis.
AB  - PURPOSE: The purpose of this study was to report the case of a patient with acute
      retinal necrosis who developed neurotoxicity while being treated with oral
      valaciclovir antiviral therapy. METHODS: Testing used was clinical examination
      including fundus photographs, renal biochemistry, cerebrospinal fluid analysis,
      and renal ultrasound. RESULTS: A 63-year-old, healthy, white woman was being
      treated with oral valaciclovir for acute retinal necrosis. Several days later,
      she developed visual hallucinations and confusion. Renal biochemistry was
      abnormal, and renal ultrasound was normal. Cerebrospinal fluid cellularity was
      normal, but cerebrospinal fluid 9-carboxymethoxymethylguanine, an aciclovir
      metabolite, level was elevated. Treatment was changed to intravenous aciclovir
      titrated based on serum aciclovir levels with intravenous fluid supplementation
      to good effect. CONCLUSION: Regular monitoring of renal function and ample fluid
      intake are important when high doses of aciclovir/valaciclovir are used, even in
      patients with no previous history of renal failure. Monitoring of serum aciclovir
      level is useful in those with renal impairment to titrate doses, and high-dose
      oral valaciclovir should be used with caution.

PMID- 25389729
TI  - Migration of ozurdex implant into the anterior chamber.
AB  - PURPOSE: The purpose of this study was to report a novel complication of Ozurdex
      implantation in which the implant migrates into the anterior chamber and to
      describe the subsequent clinical course. METHODS: After identification of the
      implant in the inferior anterior chamber, clinical photographs were obtained.
      Baseline measurements of vision, corneal thickness, and corneal cell counts were
      likewise collected. The patent was followed for clinical sequelae. RESULTS: After
      4 months, the implant was clearly observed to be degrading. Repeat corneal
      pachymetry, slit-lamp examination, and visual acuity were stable. DISCUSSION:
      Patients with a patent peripheral iridotomy who received Ozurdex intravitreal
      implants are at risk for migration of the implant into the anterior chamber.
      However, the implant itself appears to be benign, causing no detrimental effects
      to the corneal endothelium.

PMID- 25389730
TI  - Eyelid cutaneous hypopigmentation after sub-tenon triamcinolone injection after
      retinal detachment repair.
AB  - BACKGROUND: Cutaneous hypopigmentation has been reported after steroid injection.
      Sub-Tenon triamcinolone injection is often administered to control or prevent
      ocular inflammation. METHODS: Observational case report. RESULTS: Lower eyelid
      cutaneous hypopigmentation developed 6 weeks after sub-Tenon triamcinolone
      injection administered at the conclusion of scleral buckle and vitrectomy for
      retinal detachment repair. The hypopigmentation eventually resolved at 7 months
      postoperatively. CONCLUSION: Sub-Tenon triamcinolone injection at the conclusion
      of retinal surgery can cause temporary cutaneous hypopigmentation of the eyelid.
      This risk should be explained preoperatively to patients, particularly those who
      are more heavily pigmented.

PMID- 25389731
TI  - Purtscher-like retinopathy and primary hypereosinophilic syndrome association.
AB  - PURPOSE: The purpose of this study was to describe a patient who presented with a
      Purtscherlike retinopathy and subsequent diagnosis of primary hypereosinophilic
      syndrome. METHODS: Observational case report. PATIENT: A 39-year-old woman
      presented with a 10-day history of blurry vision and urticarial skin rash.
      Retinoscopic examination demonstrated bilateral cotton wool spots in the
      posterior pole, Purtscher flecken, and intraretinal hemorrhages. Workup included
      a complete history and systemic physical examination, fluorescein angiography,
      serum laboratory evaluation, magnetic resonance imaging of brain and orbits,
      pathologic analysis of skin and bone marrow biopsies, flow cytometry, and
      cytogenetic testing. RESULTS: The diagnosis given to this patient was primary
      hypereosinophilic syndrome. Review of the literature reveals one previous report
      of this association. CONCLUSION: The differential diagnosis of Purtscher
      retinopathy should include hypereosinophilic syndrome.

PMID- 25389732
TI  - Indocyanine green toxicity after macular hole surgery in both eyes.
AB  - PURPOSE: To report on a patient with bilateral macular holes who developed
      circular retinal pigment epithelial atrophy at the fovea after macular hole
      surgery using indocyanine green in both eyes. METHOD: Interventional case report.
      RESULTS: A 68-year-old woman presented with a Stage 3 macular hole in each eye.
      Complete pars plana vitrectomy with indocyanine green-assisted internal membrane
      peeling was performed. The procedures were uneventful. The concentration and the
      exposure time to intravitreal indocyanine green were tolerable. One month after
      surgery, the macular hole was closed, but underlying circular retinal pigment
      epithelial atrophy was observed in both eyes. CONCLUSION: In clinical practice,
      if indocyanine green-related ocular toxicity develops in one eye after macular
      hole surgery, care should be taken regarding indocyanine green use during surgery
      of the other eye.

PMID- 25389733
TI  - Management of a recalcitrant candidal chorioretinal abscess.
AB  - PURPOSE: To describe a case of endogenously acquired Candida albicans
      chorioretinitis that was unresponsive to aggressive local and systemic therapy.
      METHOD: Single retrospective case report and review of pertinent literature. A 42
      year-old woman with metastatic colon cancer acquired endogenous C. albicans
      chorioretinitis secondary to total parenteral nutrition after a small-bowel
      resection. RESULTS: A lesion involving the left fovea progressed despite systemic
      antifungal therapy with intravenous anidulafungin followed by oral fluconazole,
      intravenous Ambisome, and 11 total intravitreal injections of either Amphotericin
      B (5 mg each) or voriconazole (50-100 mg each). The patient underwent pars plana
      vitrectomy with subfoveal aspiration and removal of infectious material using
      submacular surgery, resulting in resolution of the infection. Postoperatively the
      patient's visual acuity was the same as before surgery (20/200 in the left eye).
      CONCLUSION: When treating endogenous fungal chorioretinitis, attention should be
      paid to both systemic treatment that has good intraocular penetration and early
      local therapy with intravitreal antifungals for sight-threatening lesions.
      Surgical intervention may also be warranted.

PMID- 25389734
TI  - Diffuse retinal capillary leakage in coats disease.
AB  - PURPOSE: Coats disease is a rare condition characterized by retinal vascular
      telangiectasia, aneurysms, and leakage from these abnormal blood vessels. We
      report the phenomenon and treatment of Coats disease with diffuse
      hyperpermeability from angiographically normal retinal capillaries. METHODS: This
      case series describes two patients with Coats disease, diagnosed based on fundus
      photography and fluorescein angiography. The first patient was treated with
      intravitreal bevacizumab and limited laser photocoagulation. The second patient
      was treated only with limited photocoagulation. RESULTS: The diffuse exudation
      from normal retinal capillaries resolved with treatment of the focal primary
      vascular Coats lesions. CONCLUSION: Vasculopathies such as Coats disease may
      produce diffuse hyperpermeability of otherwise normal capillaries in the fundus.
      Limiting treatment only to the primary Coats lesions is a minimally invasive
      strategy that preserves normal capillaries.

PMID- 25389735
TI  - Use of intraocular human recombinant tissue plasminogen activator as an adjunct
      treatment of posterior synechiae in patients with uveitis.
AB  - PURPOSE: To evaluate the effect of intracameral injection of small doses of human
      recombinant tissue plasminogen activator (hr-tPA) as an adjunct to lysing
      extensive recent-onset posterior synechiae associated with uveitis in the setting
      of impending pupillary seclusion. METHODS: This is an interventional
      retrospective case series involving three patients. All patients received an
      intracameral injection of hr-tPA while on maximum antiinflammatory therapy. Two
      patients had unilateral acute anterior uveitis with extensive (270 degrees -360
      degrees ) recent-onset posterior synechiae, while 1 patient had chronic recurrent
      anterior uveitis complicated by recent and preexisting posterior synechiae.
      RESULTS: Two patients with acute uveitis had rapid and complete synechiolysis
      (360 degrees ) after an intracameral injection of hr-tPA within 24 hours. One
      patient with acute reactivation of recurrent uveitis had subtotal (270 degrees )
      synechiolysis because of incomplete lysis of chronic synechiae. With resolution
      of inflammation, all patients regained their preuveitis visual acuity. No
      cataract or glaucoma was reported at 12-month follow-up. CONCLUSION: We evaluated
      the role of intracameral hr-tPA injections as an adjunct to maximum
      antiinflammatory therapy. We conclude that a low-dose (3 MUg) low-volume (0.05
      mL) intracameral injection of hr-tPA in patients with extensive recent-onset
      posterior synechiae associated with uveitis leads to rapid lysis of synechiae,
      reducing the risk of pupillary seclusion and associated glaucoma.

PMID- 25389736
TI  - Lipemia retinalis as a presenting feature of hypertriglyceridemia associated with
      protease inhibitors in human immunodeficiency virus-infected patients.
AB  - PURPOSE: To report two cases of lipemia retinalis in patients infected with human
      immunodeficiency virus on protease inhibitors with increased triglyceride levels.
      METHODS: Retrospective review of medical records. Two patients infected with
      human immunodeficiency virus using protease inhibitors who were diagnosed with
      severe hypertriglyceridemia based on eye findings of lipemia retinalis. RESULTS:
      One patient developed triglyceride level of >5,300 mg/dL after adding an
      integrase inhibitor to a regimen that included protease inhibitors.
      Hypertriglyceridemia was diagnosed after routine ophthalmic screening for
      cytomegalovirus retinitis revealed lipemia retinalis. Triglyceride levels
      improved significantly after both discontinuation of HIV medications and
      adjustment of cholesterol-lowering medications. Another patient developed
      triglyceride levels of >9,000 mg/dL while on protease inhibitors, which was also
      detected on routine retinal examination. Shortly after the diagnosis, he
      experienced acute coronary syndrome and cardiac arrest requiring plasmapheresis
      and emergent bypass surgery. CONCLUSION: Lipemia retinalis is rare but may be a
      presenting sign of severe hypertriglyceridemia in patients infected with human
      immunodeficiency virus. Recognition of this condition during the ophthalmic
      examination can lead to diagnosis and may allow for treatment before the
      development of life-threatening complications, such as pancreatitis and acute
      coronary syndrome.

PMID- 25389737
TI  - Restoration of vision after surgical removal of an intraocular needlefish jaw.
AB  - PURPOSE: To describe the case of a globe-penetrating intraocular needlefish
      injury. METHODS: Clinicopathologic case report. RESULTS: A 38-year-old man had a
      globe-penetrating injury while swimming without eye protection in the Caribbean
      Sea. The foreign body was impaled in the nasal retina. After surgical removal,
      retinal repair, and subsequent cataract surgery, the best-corrected visual acuity
      was 20/20 in the affected eye. Histopathologic examination of the foreign body
      was consistent with a needlefish jaw. CONCLUSION: This is the first reported case
      of a successful visual outcome after the surgical removal of an intraocular
      needlefish jaw. Furthermore, we advise that ophthalmologists should be
      recommending eye protection to people swimming in waters endemic to this
      dangerous fish.

PMID- 25389738
TI  - Layer cake-silicone oil under the internal limiting membrane in an optic pit eye.
AB  - PURPOSE: To describe a case of sub-internal limiting membrane (ILM) silicone oil
      dislocation in a patient with optic pit of the disk pathology. METHODS:
      Interventional case report. The patient had been previously subjected to silicone
      oil surgery because of pit of the disk-associated retinal detachment. After
      silicone oil removal, persistent oil emulsifications were diagnosed within the
      posterior pole. Both the spatial location within the retina and the
      interpretation of preoperative spectral-domain optical coherence tomography
      images were impaired because of posterior capsule opacification. RESULTS: Upon
      explorative revitrectomy, mobile silicone oil appeared underneath a clear
      membrane. Internal limiting membrane peeling led to silicone oil ascension into
      the vitreous cavity. The macular area appeared atrophic after oil removal.
      Previously described formation of internal limiting membrane ridges in optic pit
      with subsequent emergence of sub-internal limiting membrane cavities may have
      facilitated silicone oil dislocation into sub-internal limiting membrane space
      through the optic pit. CONCLUSION: Our findings add to the features of possible
      spatial fluid dislocations in patients with pit of the disk pathology. Complete
      internal limiting membrane removal and careful evaluation of tamponade use, are
      desirable in surgical treatment of optic pit cases.

PMID- 25389739
TI  - Bilateral central retinal artery occlusions and hughes syndrome.
AB  - PURPOSE: The purpose of this study to report a case of bilateral retinal artery
      occlusions in a patient with systemic lupus erythematosus and antiphospholipid
      antibodies. METHODS: A 28-year-old woman with systemic lupus erythematosus
      presented with sudden painless bilateral vision loss. Clinical examination and
      flourescein angiography were performed, and a diagnosis of bilateral central
      retinal artery occlusions was made. Laboratory evaluations were ordered. RESULTS:
      Laboratory evaluation revealed the presence of antiphospholipid antibodies.The
      patient was treated with corticosteroids, azathioprine, aspirin, and warfarin.
      The patient's visual acuity gradually improved over 2 weeks and then remained
      stable for 6 months without any further thrombotic events. CONCLUSION: The
      presence of bilateral retinal artery occlusions in a young patient should prompt
      an immediate evaluation for antiphospholipid antibodies, especially if the
      patient has been previously diagnosed with systemic lupus erythematosus.
      Correctly diagnosing patients with antiphospholipid antibodies is important
      because it implies the need for long-term anticoagulative and antiaggregative
      therapies to reduce the patient's risk of recurrent, life-threatening, thrombotic
      events.

PMID- 25389740
TI  - Orbital hemorrhage after intravitreal injection.
AB  - PURPOSE: To describe a case of orbital hemorrhage after the administration of
      intravitreal ranibizumab. METHODS: Retrospective chart review of one case.
      RESULTS: A 73-year-old woman with a history of atrial fibrillation on coumadin
      anticoagulation (international normalized ratio = 3.4) presented with decreased
      vision and metamorphopsia in her right eye for 2 weeks duration. Examination was
      consistent with a diagnosis of neovascular age-related macular degeneration in
      the right eye. After one injection of intravitreal ranibizumab, she developed a
      bullous subconjunctival hemorrhage that extended into an orbital hemorrhage.
      CONCLUSION: Intravitreal injection may result in orbital hemorrhage, particularly
      in the anticoagulated patient.

PMID- 25389741
TI  - Spectral-domain optical coherence tomography findings in acute retinal pigment
      epitheliitis.
AB  - PURPOSE: To report new findings revealed by spectral-domain optical coherence
      tomography in a patient with bilateral acute retinal pigment epitheliitis.
      METHODS: A patient presented with bilateral central scotoma and clinical and
      angiographic findings consistent with acute retinal pigment epitheliitis.
      Spectral-domain optical coherence tomography was performed at presentation and
      throughout follow-up. RESULTS: Early spectral-domain optical coherence tomography
      showed hyperreflectivity throughout the full thickness of the foveola, suggesting
      a full-thickness foveal inflammatory disorder. Later images provide insight into
      the natural course of acute retinal pigment epitheliitis and eventually showed a
      small outer retinal defect similar to that reported in some patients with macular
      microhole or foveal red spot. CONCLUSION: Acute retinal pigment epitheliitis is a
      macular inflammatory disorder that can involve the full thickness of the fovea
      and underlying retinal pigment epithelium and may result in a small defect in the
      outer retina similar to that reported in some patients with macular microhole or
      foveal red spot.

PMID- 25389742
TI  - Metastatic choriocarcinoma to the choroid with concurrent optic nerve
      involvement: a case report and review of the literature.
AB  - PURPOSE: To describe a case of choroidal metastasis of choriocarcinoma, which
      presented as a rapidly progressive hemorrhagic retinal detachment with concurrent
      optic nerve involvement suggestive of inflammation or metastasis. METHOD: This is
      a case report of a 43-year-old patient with a known history of choriocarcinoma
      metastases to both lungs who presented with 1 week of right eye pain and
      decreased vision. Dilated fundus examination was significant for a large,
      bullous, hemorrhagic retinal detachment, with the appearance of an underlying
      choroidal mass in the superonasal retina. Magnetic resonance imaging result was
      significant for a 1.6 * 1.3-cm heterogeneous mass in the right globe, suggestive
      of metastasis, and inflammatory changes in the sclera, optic nerve, and optic
      nerve sheath. Additionally, hemorrhagic metastases were found in the right
      occipital and left frontal lobes. RESULTS: To our knowledge, this is the first
      case of metastatic choriocarcinoma to the choroid with concurrent optic nerve
      involvement. CONCLUSION: Choroidal metastases may be diagnosed in the setting of
      more widespread central nervous system involvement and should be investigated
      accordingly.

PMID- 25389743
TI  - Retinoschisis detected by spectral-domain optical coherence tomography in von
      hippel-lindau disease.
AB  - PURPOSE: To report the presence of retinoschises in a case of von Hippel-Lindau
      disease detected by spectral-domain optical coherence tomography. METHODS: Case
      report of a 23-year-old man with von Hippel-Lindau disease who was seen for a
      regular follow-up examination. RESULTS: Ophthalmoscopy showed several retinal
      capillary hemangioblastomas in both eyes. Spectral-domain optical coherence
      tomography showed retinoschises around the retinal capillary hemangioblastoma and
      also around the feeder and draining vessels of the peripheral larger
      hemangioblastoma. The retinoschises were found under the internal limiting
      membrane and also in the inner and outer retinal layers. Intraretinal columns
      were observed in the retinoschises. CONCLUSION: Our observations show that
      retinoschises can develop in eyes with von Hippel-Lindau disease. The
      extensiveness of the retinoschises suggests that the retina is fragile in von
      Hippel-Lindau disease.

PMID- 25389744
TI  - Transient retinal venous and arterial occlusive events in a case of sneddon
      syndrome.
AB  - PURPOSE: We report a case with venous and arterial occlusive events in Sneddon
      syndrome and describe the accompanying fluorescein angiographic findings.
      METHODS: Observational case report. RESULTS: This 27-year-old white woman
      developed acute visual loss and a central scotoma in her right eye in consequence
      of a central retinal vein occlusion and, 2 years later, a paracentral scotoma in
      her left eye in consequence of an incomplete branch retinal artery occlusion.
      Fluorescein angiography revealed an unusual laminar hyperfluorescence downstream
      to the arterial obstruction. Patient became seropositive for anticardiolipin
      antibodies in the course of the 2 years. Eventually, the ocular together with
      neurologic and cardiac manifestations led to the diagnosis of Sneddon syndrome.
      CONCLUSION: Sneddon syndrome should be considered in any ocular vascular
      occlusive event under the age of 50 years. In addition, this case reports for the
      first time unusual fluorescein angiographic findings of incomplete branch retinal
      arterial occlusions, possibly associated with endothelial damage in Sneddon
      syndrome.

PMID- 25389745
TI  - Ocular decompression retinopathy after bleb needling in a patient with extremely
      high intraocular pressure.
AB  - PURPOSE: To report a case of ocular decompression retinopathy after bleb needling
      in a patient with extremely high intraocular pressure. METHODS: Case report of a
      55-year-old man who had undergone trabeculectomy for neovascular glaucoma and
      bleb needling to lower intraocular pressure. RESULTS: During the procedure, the
      anterior chamber collapsed suddenly as a result of overdrainage, and the
      intraocular pressure decreased rapidly from 60 mmHg to 2 mmHg. Funduscopy
      performed the next day showed multiple intraretinal hemorrhages in all quadrants.
      Fluorescein angiography showed no evidence of occluded retinal vessels. He had no
      history of any bleeding disorder. Decompression retinopathy was diagnosed.
      CONCLUSION: Decompression retinopathy can occur after bleb needling, which is
      often required after trabeculectomy to restore bleb function.

PMID- 25389746
TI  - Rosai-dorfman disease diagnosed because of bilateral choroidal masses.
AB  - PURPOSE: To describe a case of bilateral choroidal masses leading to the
      diagnosis of Rosai-Dorfman disease. METHOD: Case report. Color photographs,
      fluorescein angiography, autofluorescence, indocyanine green angiography, and
      high-definition optical coherence tomography imaging of both eyes and computed
      tomography and biopsy of pelvis mass were performed. A 47-year-lady presented
      with unknown choroidal masses in both eyes. She had no visual complaints. Her
      medical history was noncontributory. RESULTS: Workup included a computed
      tomography of the chest and abdomen that demonstrated soft tissue masses in the
      renal pelvis bilaterally. A core needle biopsy from the renal mass demonstrated
      numerous histiocytoid that were positive for CD163 and S100 protein. CONCLUSION:
      Based on this spectrum of findings, the diagnosis of Rosai-Dorfman disease was
      made. To date, the patient has been followed-up for 3 years without medical
      intervention and without visual deterioration. Careful follow-up is a reasonable
      management if patients are asymptomatic.

PMID- 25389747
TI  - Presumed bilateral choroidal metastases from mucoepidermoid carcinoma of the
      submandibular gland.
AB  - PURPOSE: To report a case of presumed bilateral choroidal metastases from
      mucoepidermoid carcinoma of submandibular gland. METHODS: Case report. A 52-year
      old lady with history of left submandibular gland mucoepidermoid carcinoma
      developed bilateral choroidal metastases unresponsive to chemotherapy. She
      presented with a 3-week history of left eye pain. Fundoscopy revealed bilateral
      yellowish choroidal lesions associated with inferior exudative retinal
      detachment. B-scan ultrasonography showed high internal reflectivity of both
      lesions. Fluorescein angiography revealed pinpoint foci of hyperfluorescence over
      the choroidal lesion with late leakage. The patient declined positron emission
      tomography scan, radiotherapy, and surgical intervention. She eventually
      succumbed 5 months after the initial presentation. RESULT: Our case is the first
      case report on clinically presumed bilateral choroidal metastases from
      mucoepidermoid carcinoma of the submandibular gland. CONCLUSION: There are few
      reported cases of ocular metastasis from salivary gland tumors, mostly adenoid
      cystic carcinoma. To the best of our knowledge, this is the first reported case
      of bilateral choroidal metastases from mucoepidermoid carcinoma of the
      submandibular gland.

PMID- 25389748
TI  - Syphilitic chorioretinitis mimicking an anterior chiasmal syndrome.
AB  - PURPOSE: To report a case of syphilitic chorioretinitis mimicking an anterior
      chiasmal syndrome. METHODS: Observational case report. RESULTS: A 74-year-old man
      with a remote history of syphilitic chorioretinitis was noted to have an apparent
      junctional scotoma on a screening Humphrey visual field. Subsequent magnetic
      resonance imaging of the brain was normal, and the patient was referred for neuro
      ophthalmologic evaluation. The fundus examination and a fluorescein angiogram
      demonstrated that the pattern of chorioretinal scarring corresponded to the
      visual field defects in both eyes. CONCLUSION: Syphilis, the great masquerader,
      may cause retinal disease that mimics a neurologic visual field defect.

PMID- 25389749
TI  - EXAFS study of the speciation of protactinium(V) in aqueous hydrofluoric acid
      solutions.
AB  - The speciation of protactinium(V) in hydrofluoric acid (HF) solutions was studied
      using X-ray absorption spectroscopy. Extended X-ray absorption fine structure
      measurements were performed on an aqueous solution of 0.05 M protactinium(V) with
      various HF concentrations ranging from 0.5 to 27 M in order to probe the
      protactinium coordination sphere with respect to the identity and number of
      coordinating ligands. The resulting fits to the spectra suggest the presence of
      an eight-coordinate homoleptic fluoro complex in highly concentrated fluoride
      solutions (27 M), with equilibrium between seven- and eight-coordinate fluoro
      complexes at moderate acidities, and in more dilute solutions, results indicate
      that one water molecule is likely to replace a fluoride in the first coordination
      sphere, at a distance of 2.54-2.57 A. Comparisons of this chemistry with group V
      metals, niobium and tantalum, are presented, and the potential implications for
      these results on the hydrolytic behavior of protactinium in aqueous systems are
      discussed. 

PMID- 25389750
TI  - Phylogeography of Rhodiola kirilowii (Crassulaceae): a story of Miocene
      divergence and quaternary expansion.
AB  - The evolution and current distribution of the Sino-Tibetan flora have been
      greatly affected by historical geological events, such as the uplift of the
      Qinghai-Tibetan Plateau (QTP), and Quaternary climatic oscillations. Rhodiola
      kirilowii, a perennial herb with its distribution ranging from the southeastern
      QTP and the Hengduan Mountains (HM) to adjacent northern China and central Asia,
      provides an excellent model to examine and disentangle the effect of both
      geological orogeny and climatic oscillation on the evolutionary history of
      species with such distribution patterns. We here conducted a phylogeographic
      study using sequences of two chloroplast fragments (trnL-F and trnS-G) and
      internal transcribed spacers in 29 populations of R. kirilowii. A total of 25
      plastid haplotypes and 12 ITS ribotypes were found. Molecular clock estimation
      revealed deep divergence between the central Asian populations and other
      populations from the HM and northern China; this split occurred ca. 2.84 million
      year ago. The majority of populations from the mountains of northern China were
      dominated by a single haplotype or ribotype, while populations of the HM harbored
      both high genetic diversity and high haplotype diversity. This distribution
      pattern indicates that HM was either a diversification center or a refugium for
      R. kirilowii during the Quaternary climatic oscillations. The present
      distribution of this species on mountains in northern China may have resulted
      from a rapid glacial population expansion from the HM. This expansion was
      confirmed by the mismatch distribution analysis and negative Tajima's D and Fu's
      FS values, and was dated to ca. 168 thousand years ago. High genetic diversity
      and population differentiation in both plastid and ITS sequences were revealed;
      these imply restricted gene flow between populations. A distinct isolation-by
      distance pattern was suggested by the Mantel test. Our results show that in old
      lineages, populations may harbour divergent genetic forms that are sufficient to
      maintain or even increase overall genetic diversity despite fragmentation and low
      within-population variation. 

PMID- 25389751
TI  - Closing the achievement gap through modification of neurocognitive and
      neuroendocrine function: results from a cluster randomized controlled trial of an
      innovative approach to the education of children in kindergarten.
AB  - Effective early education is essential for academic achievement and positive life
      outcomes, particularly for children in poverty. Advances in neuroscience suggest
      that a focus on self-regulation in education can enhance children's engagement in
      learning and establish beneficial academic trajectories in the early elementary
      grades. Here, we experimentally evaluate an innovative approach to the education
      of children in kindergarten that embeds support for self-regulation, particularly
      executive functions, into literacy, mathematics, and science learning activities.
      Results from a cluster randomized controlled trial involving 29 schools, 79
      classrooms, and 759 children indicated positive effects on executive functions,
      reasoning ability, the control of attention, and levels of salivary cortisol and
      alpha amylase. Results also demonstrated improvements in reading, vocabulary, and
      mathematics at the end of kindergarten that increased into the first grade. A
      number of effects were specific to high-poverty schools, suggesting that a focus
      on executive functions and associated aspects of self-regulation in early
      elementary education holds promise for closing the achievement gap. 

PMID- 25389752
TI  - Sediment delivery ratio of single flood events and the influencing factors in a
      headwater basin of the Chinese Loess Plateau.
AB  - Little is known about the sediment delivery of single flood events although it
      has been well known that the sediment delivery ratio at the inter-annual time
      scale is close to 1 in the Chinese Loess Plateau. This study examined the
      sediment delivery of single flood events and the influencing factors in a
      headwater basin of the Loess Plateau, where hyperconcentrated flows are dominant.
      Data observed from plot to subwatershed over the period from 1959 to 1969 were
      presented. Sediment delivery ratio of a single event (SDRe) was calculated as the
      ratio of sediment output from the subwatershed to sediment input into the
      channel. It was found that SDRe varies greatly for small events (runoff depth <5
      mm or rainfall depth <30 mm) and remains fairly constant (approximately between
      1.1 and 1.3) for large events (runoff depth >5 mm or rainfall depth >30 mm). We
      examined 11 factors of rainfall (rainfall amount, rainfall intensity, rainfall
      kinetic energy, rainfall erosivity and rainfall duration), flood (area-specific
      sediment yield, runoff depth, peak flow discharge, peak sediment concentration
      and flood duration) and antecedent land surface (antecedent precipitation) in
      relation to SDRe. Only the peak sediment concentration significantly correlates
      with SDRe. Contrary to popular belief, channel scour tends to occur in cases of
      higher peak sediment concentrations. Because small events also have chances to
      attain a high sediment concentration, many small events (rainfall depth <20 mm)
      are characterized by channel scour with an SDRe larger than 1. Such observations
      can be related to hyperconcentrated flows, which behave quite differently from
      normal stream flows. Our finding that large events have a nearly constant SDRe is
      useful for sediment yield predictions in the Loess Plateau and other regions
      where hyperconcentrated flows are well developed. 

PMID- 25389753
TI  - Spectral effects on Symbiodinium photobiology studied with a programmable light
      engine.
AB  - The spectral light field of Symbiodinium within the tissue of the coral animal
      host can deviate strongly from the ambient light field on a coral reef and that
      of artificial light sources used in lab studies on coral photobiology. Here, we
      used a novel approach involving light microsensor measurements and a programmable
      light engine to reconstruct the spectral light field that Symbiodinium is exposed
      to inside the coral host and the light field of a conventional halogen lamp in a
      comparative study of Symbiodinium photobiology. We found that extracellular gross
      photosynthetic O2 evolution was unchanged under different spectral illumination,
      while the more red-weighted halogen lamp spectrum decreased PSII electron
      transport rates and there was a trend towards increased light-enhanced dark
      respiration rates under excess irradiance. The approach provided here allows for
      reconstructing and comparing intra-tissue coral light fields and other complex
      spectral compositions of incident irradiance. This novel combination of sensor
      technologies provides a framework to studying the influence of macro- and
      microscale optics on Symbiodinium photobiology with unprecedented spectral
      resolution. 

PMID- 25389756
TI  - Combined chemotherapy and surgery in primary small cell carcinoma of the
      esophagus.
AB  - AIM: The aim of the study was to retrospectively analyze survival outcomes of
      surgery combined with chemotherapy in primary small cell carcinoma of esophagus.
      METHODS: From January 2000 to December 2009, all patients with esophageal
      carcinoma who had undergone esophagectomy were selected from the Department of
      Thoracic Surgery, Henan Cancer Hospital, China. They were subjected to trans-left
      thoracic incision esophagectomy. For tumors located in the upper third thoracic
      esophagus, trans-right thoracic incision and abdomen incision esophagectomy was
      selected. We chose etoposide (EP) regimen for chemotherapy. RESULTS: The
      percentage of pure esophagus small cell carcinoma (57 cases) in all patients who
      underwent esophagectomy was 1.1%. The median survival time was 45 months. In
      stage I, II, III, the survival rate was 25%, 5.9%, 4.3% respectively. In the
      subgroup analysis, overall median survival time of surgery was 23.2 months while
      the time of combined surgery and chemotherapy was 60.7 months (P<0.01). For stage
      I patients, combined therapy was associated with a significant longer median
      survival time (81.9 months) than surgery alone (22.3 months) (P<0.01).
      CONCLUSION: Systemic chemotherapy of cisplatin-based regimens should be
      considered as important treatment options to improve survival outcome, even early
      small cell esophageal cancer.

PMID- 25389754
TI  - High risk of lead contamination for scavengers in an area with high moose hunting
      success.
AB  - Top predators and scavengers are vulnerable to pollutants, particularly those
      accumulated along the food chain. Lead accumulation can induce severe disorders
      and alter survival both in mammals (including humans) and in birds. A potential
      source of lead poisoning in wild animals, and especially in scavengers, results
      from the consumption of ammunition residues in the tissues of big game killed by
      hunters. For two consecutive years we quantified the level lead exposure in
      individuals of a sentinel scavenger species, the common raven (Corvus corax),
      captured during the moose (Alces alces) hunting season in eastern Quebec, Canada.
      The source of the lead contamination was also determined using stable isotope
      analyses. Finally, we identified the different scavenger species that could
      potentially be exposed to lead by installing automatic cameras targeting moose
      gut piles. Blood lead concentration in ravens increased over time, indicating
      lead accumulation over the moose-hunting season. Using a contamination threshold
      of 100 ug x L(-1), more than 50% of individuals were lead-contaminated during the
      moose hunting period. Lead concentration was twice as high in one year compared
      to the other, matching the number of rifle-shot moose in the area. Non
      contaminated birds exhibited no ammunition isotope signatures. The isotope
      signature of the lead detected in contaminated ravens tended towards the
      signature from lead ammunition. We also found that black bears (Ursus
      americanus), golden eagles and bald eagles (Aquila chrysaetos and Haliaeetus
      leucocephalus, two species of conservation concern) scavenged heavily on moose
      viscera left by hunters. Our unequivocal results agree with other studies and
      further motivate the use of non-toxic ammunition for big game hunting.

PMID- 25389757
TI  - Application of vacuum sealing drainage in the treatment of internal fixation
      instrument exposure after early postoperative infection.
AB  - AIM: This retrospective study aimed to investigate the effect of vacuum sealing
      drainage (VSD) in the management of fractured patients with internal fixation
      instrument exposure caused by early postoperative infection after open reduction
      and internal fixation (ORIF). METHODS: Fourteen patients (11 men, 3 women, age
      range 9-63 years) with spinal and extremities fractures were enrolled in this
      study, including atlanto-axial fracture (N.=1), thoraco-lumbar fracture (N.=1),
      humerus fracture (N.=1), femoral fracture (N.=2), humerus fracture together with
      femoral fracture (N.=1), fracture of tibia and fibula (N.=3), L1 vertebral
      fracture together with tibia and fibula fracture (N.=2), L1 vertebral fracture
      (N.=2) and L1 vertebral fracture complicated by type II diabetes (N.=1).
      Infections occurred at the surgical incisions 1-7 days after ORIF operation. Deep
      spread of the infection caused exposure of internal fixation device. All patients
      underwent local debridement with retention of internal fixation device. VSD foam
      dressings containing the drainage tube were placed into the wound, covering
      external fixation devices and fully eliminating the dead space of soft tissue to
      avoid effusion. Continuous drainage and VSD irrigation was performed for 24 h
      with regular replacement of VSD. RESULTS: After 14-43 days of VSD treatment,
      internal fixation devices were covered by healthy granulation tissue and complete
      wound healing was achieved. During a postoperative follow-up period of between 2
      to 52 months, physical examinations and imaging studies of all patients showed
      good functional recovery, no loosening of internal fixation devices, and no
      systemic or local infection. CONCLUSION: The use of VSD, while retaining the
      internal fixation device can be safe and effective with earlier wound healing and
      functional recovery.

PMID- 25389758
TI  - Upk3b is dispensable for development and integrity of urothelium and mesothelium.
AB  - The mesothelium, the lining of the coelomic cavities, and the urothelium, the
      inner lining of the urinary drainage system, are highly specialized epithelia
      that protect the underlying tissues from mechanical stress and seal them from the
      overlying fluid space. The development of these epithelia from simple precursors
      and the molecular characteristics of the mature tissues are poorly analyzed.
      Here, we show that uroplakin 3B (Upk3b), which encodes an integral membrane
      protein of the tetraspanin superfamily, is specifically expressed both in
      development as well as under homeostatic conditions in adult mice in the
      mesothelia of the body cavities, i.e., the epicardium and pericardium, the pleura
      and the peritoneum, and in the urothelium of the urinary tract. To analyze Upk3b
      function, we generated a creERT2 knock-in allele by homologous recombination in
      embryonic stem cells. We show that Upk3bcreERT2 represents a null allele despite
      the lack of creERT2 expression from the mutated locus. Morphological,
      histological and molecular analyses of Upk3b-deficient mice did not detect
      changes in differentiation or integrity of the urothelium and the mesothelia that
      cover internal organs. Upk3b is coexpressed with the closely related Upk3a gene
      in the urothelium but not in the mesothelium, leaving the possibility of a
      functional redundancy between the two genes in the urothelium only. 

PMID- 25389759
TI  - Identification and characterization of HTLV-1 HBZ post-translational
      modifications.
AB  - Human T-cell leukemia virus type-1 (HTLV-1) is estimated to infect 15-25 million
      people worldwide, with several areas including southern Japan and the Caribbean
      basin being endemic. The virus is the etiological agent of debilitating and fatal
      diseases, for which there is currently no long-term cure. In the majority of
      cases of leukemia caused by HTLV-1, only a single viral gene, hbz, and its
      cognate protein, HBZ, are expressed and their importance is increasingly being
      recognized in the development of HTLV-1-associated disease. We hypothesized that
      HBZ, like other HTLV-1 proteins, has properties and functions regulated by post
      translational modifications (PTMs) that affect specific signaling pathways
      important for disease development. To date, PTM of HBZ has not been described. We
      used an affinity-tagged protein and mass spectrometry method to identify seven
      modifications of HBZ for the first time. We examined how these PTMs affected the
      ability of HBZ to modulate several pathways, as measured using luciferase
      reporter assays. Herein, we report that none of the identified PTMs affected HBZ
      stability or its regulation of tested pathways. 

PMID- 25389760
TI  - Influence of group size on the success of wolves hunting bison.
AB  - An intriguing aspect of social foraging behaviour is that large groups are often
      no better at capturing prey than are small groups, a pattern that has been
      attributed to diminished cooperation (i.e., free riding) in large groups.
      Although this suggests the formation of large groups is unrelated to prey
      capture, little is known about cooperation in large groups that hunt hard-to
      catch prey. Here, we used direct observations of Yellowstone wolves (Canis lupus)
      hunting their most formidable prey, bison (Bison bison), to test the hypothesis
      that large groups are more cooperative when hunting difficult prey. We quantified
      the relationship between capture success and wolf group size, and compared it to
      previously reported results for Yellowstone wolves hunting elk (Cervus elaphus),
      a prey that was, on average, 3 times easier to capture than bison. Whereas
      improvement in elk capture success levelled off at 2-6 wolves, bison capture
      success levelled off at 9-13 wolves with evidence that it continued to increase
      beyond 13 wolves. These results are consistent with the hypothesis that hunters
      in large groups are more cooperative when hunting more formidable prey. Improved
      ability to capture formidable prey could therefore promote the formation and
      maintenance of large predator groups, particularly among predators that
      specialize on such prey. 

PMID- 25389761
TI  - Habitat capacity for cougar recolonization in the Upper Great Lakes region.
AB  - BACKGROUND: Recent findings indicate that cougars (Puma concolor) are expanding
      their range into the midwestern United States. Confirmed reports of cougar in
      Michigan, Minnesota, and Wisconsin have increased dramatically in frequency
      during the last five years, leading to speculation that cougars may re-establish
      in the Upper Great Lakes (UGL) region, USA. Recent work showed favorable cougar
      habitat in northeastern Minnesota, suggesting that the northern forested regions
      of Michigan and Wisconsin may have similar potential. Recolonization of cougars
      in the UGL states would have important ecological, social, and political impacts
      that will require effective management. METHODOLOGY/PRINCIPAL FINDINGS: Using
      Geographic Information Systems (GIS), we extended a cougar habitat model to
      Michigan and Wisconsin and incorporated primary prey densities to estimate the
      capacity of the region to support cougars. Results suggest that approximately 39%
      (>58,000 km2) of the study area could support cougars, and that there is
      potential for a population of approximately 500 or more animals. An exploratory
      validation of this habitat model revealed strong association with 58 verified
      cougar locations occurring in the study area between 2008 and 2013.
      CONCLUSIONS/SIGNIFICANCE: Spatially explicit information derived from this study
      could potentially lead to estimation of a viable population, delineation of
      possible cougar-human conflict areas, and the targeting of site locations for
      current monitoring. Understanding predator-prey interactions, interspecific
      competition, and human-wildlife relationships is becoming increasingly critical
      as top carnivores continue to recolonize the UGL region.

PMID- 25389763
TI  - Structural mimics of viruses through peptide/DNA co-assembly.
AB  - A synthetic mimic of viral structure has been constructed by the synergistic co
      assembly of a 16-amino acid peptide and plasmid DNA. The rational design of this
      short peptide, including segments for binding DNA and forming beta-sheet, is
      inspired by viral capsid protein. The resulting nanostructures, which we term
      nanococoons, appear as ellipsoids of virus-like dimension (65 * 47 nm) and
      display repeating stripes of ~4 nm wide. We propose that the co-assembly process
      involves DNA as a template to assist the organization of peptide strands by
      electrostatic interaction, while the bilayer beta-sheets and their lateral
      association stabilize the peptide "capsid" and organize the DNA within. The
      hierarchy affords an extremely stable structure, protecting peptide and DNA
      against enzymatic digestion. It opens a new and facile avenue to fabricate viral
      alternatives with diverse functions. 

PMID- 25389764
TI  - Optical engineering of uniformly decorated graphene oxide nanoflakes via in situ
      growth of silver nanoparticles with enhanced plasmonic resonance.
AB  - A nanocomposite of silver-nanoparticle-decorated graphene oxide (GO-Ag NPs),
      enhanced by the surface plasmon resonance (SPR) effect, improved the performance
      of polymer solar cells (PSCs). The GO-Ag NPs were fabricated in situ via
      ultraviolet (UV) irradiation (254 nm) of GO and an aqueous solution of AgNO3. The
      photoexcited GO accelerated reduction of Ag(+) ions into silver nanoparticles (Ag
      NPs) upon UV irradiation, and the Ag NPs spontaneously deposited on the GO
      nanoflakes because the numerous functional groups on GO enable efficient
      adsorption of Ag(+) ions and Ag NPs via electrostatic interactions. The strong
      coupling between the SPR effect of GO-Ag NPs and incident light offers the
      probability of improved light absorption and corresponding exciton generation
      rate with enhanced charge collection, resulting in significant enhancement in
      short-circuit current density and power conversion efficiency (PCE). Therefore,
      the PCE of PSCs based on poly[4,8-bis(2-ethylhexylthiophene-5-yl)-benzo[1,2-b:4,5
      b]dithiophene-2,6-diyl]-alt-[2-(2-ethylhexanoyl)thieno[3,4-b]thiophen-4,6-diyl]
      and [6,6]-phenyl C71-butyric acid methyl ester has been substantially elevated to
      7.54% from 6.58% by introducing GO-Ag NPs at the indium tin oxide/poly(3,4
      ethylenedioxythiophene):polystyrene sulfonic acid interface. In addition, the
      excellent properties of GO-Ag NPs, including its simple preparation,
      processability in aqueous solution, cost-effectiveness, and sustainability, make
      it suitable for the roll-to-roll manufacturing of PSCs. 

PMID- 25389765
TI  - Trantinterol, a novel beta2-adrenoceptor agonist, noncompetitively inhibits P
      glycoprotein function in vitro and in vivo.
AB  - P-glycoprotein (P-gp)-mediated drug-drug interactions are important factors
      causing adverse effects of drugs in clinical use. The aim of this study was to
      determine whether trantinterol (also known as SPFF), a novel beta2-adrenoceptor
      agonist, was a P-gp inhibitor or substrate. The results showed that trantinterol
      was not a substrate of P-gp but increased rhodamine 123 (Rho 123) uptake by MDCK
      MDR1 cells and decreased the efflux transport of both Rho 123 and cyclosporine A
      (CsA) in bidirectional transport studies across MDCK-MDR1 cell monolayers. This
      suggested that trantinterol was a P-gp inhibitor but not a P-gp substrate. The
      mechanism of inhibition was investigated in the P-gp-Glo assay system, where it
      was found that trantinterol inhibited P-gp ATPase activity in a dose-dependent
      manner. A subsequent study using the antibody binding assay with the conformation
      sensitive P-gp-specific antibody UIC2 confirmed that trantinterol decreased UIC2
      binding at 10 MUM in contrast to the competitive inhibitor, verapamil. This
      suggested that trantinterol was a noncompetitive inhibitor of P-gp. Finally, a
      pharmacokinetic study in rat showed that trantinterol significantly increased the
      area under the plasma concentration-time curve (AUC) and maximum plasma
      concentration (Cmax) of digoxin and paclitaxel (PAC), and the Cmax of
      cyclosporine A (CsA). In summary, trantinterol is a potent noncompetitive P-gp
      inhibitor which may increase the bioavailability of other P-gp substrate drugs
      coadministered with it. 

PMID- 25389766
TI  - Embodying compassion: a virtual reality paradigm for overcoming excessive self
      criticism.
AB  - Virtual reality has been successfully used to study and treat psychological
      disorders such as phobias and posttraumatic stress disorder but has rarely been
      applied to clinically-relevant emotions other than fear and anxiety. Self
      criticism is a ubiquitous feature of psychopathology and can be treated by
      increasing levels of self-compassion. We exploited the known effects of
      identification with a virtual body to arrange for healthy female volunteers high
      in self-criticism to experience self-compassion from an embodied first-person
      perspective within immersive virtual reality. Whereas observation and practice of
      compassionate responses reduced self-criticism, the additional experience of
      embodiment also increased self-compassion and feelings of being safe. The results
      suggest potential new uses for immersive virtual reality in a range of clinical
      conditions. 

PMID- 25389767
TI  - Preventive effect of Daiokanzoto (TJ-84) on 5-fluorouracil-induced human gingival
      cell death through the inhibition of reactive oxygen species production.
AB  - Daiokanzoto (TJ-84) is a traditional Japanese herbal medicine (Kampo
      formulation). While many Kampo formulations have been reported to regulate
      inflammation and immune responses in oral mucosa, there is no evidence to show
      that TJ-84 has beneficial effects on oral mucositis, a disease resulting from
      increased cell death induced by chemotherapeutic agents such as 5-fluorouracil (5
      FU). In order to develop effective new therapeutic strategies for treating oral
      mucositis, we investigated (i) the mechanisms by which 5-FU induces the death of
      human gingival cells and (ii) the effects of TJ-84 on biological events induced
      by 5-FU. 5-FU-induced lactate dehydrogenase (LDH) release and pore formation in
      gingival cells (Sa3 cell line) resulted in cell death. Incubating the cells with
      5-FU increased the expression of nucleotide-binding domain and leucine-rich
      repeat containing PYD-3 (NLRP3) and caspase-1. The cleavage of caspase-1 was
      observed in 5-FU-treated cells, which was followed by an increased secretion of
      interleukin (IL)-1beta. The inhibition of the NLRP3 pathway slightly decreased
      the effects of 5-FU on cell viability and LDH release, suggesting that NLRP3 may
      be in part involved in 5-FU-induced cell death. TJ-84 decreased 5-FU-induced LDH
      release and cell death and also significantly inhibited the depolarization of
      mitochondria and the up-regulation of 5-FU-induced reactive oxygen species (ROS)
      and nitric oxide (NO) production. The transcriptional factor, nuclear factor
      kappaB (NF-kappaB) was not involved in the 5-FU-induced cell death in Sa3 cells.
      In conclusion, we provide evidence suggesting that the increase of ROS production
      in mitochondria, rather than NLRP3 activation, was considered to be associated
      with the cell death induced by 5-FU. The results also suggested that TJ-84 may
      attenuate 5-FU-induced cell death through the inhibition of mitochondrial ROS
      production. 

PMID- 25389769
TI  - From cognitive maps to cognitive graphs.
AB  - We investigate the structure of spatial knowledge that spontaneously develops
      during free exploration of a novel environment. We present evidence that this
      structure is similar to a labeled graph: a network of topological connections
      between places, labeled with local metric information. In contrast to route
      knowledge, we find that the most frequent routes and detours to target locations
      had not been traveled during learning. Contrary to purely topological knowledge,
      participants typically traveled the shortest metric distance to a target, rather
      than topologically equivalent but longer paths. The results are consistent with
      the proposal that people learn a labeled graph of their environment. 

PMID- 25389768
TI  - CYLD negatively regulates nontypeable Haemophilus influenzae-induced IL-8
      expression via phosphatase MKP-1-dependent inhibition of ERK.
AB  - Nontypeable Haemophilus influenzae (NTHi), a Gram-negative bacterium, is the
      primary cause of otitis media in children and the exacerbation of chronic
      obstructive pulmonary disease in adults. A hallmark of both diseases is an
      overactive inflammatory response, including the upregulation of chemokines, such
      as interleukin-8 (IL-8). An appropriate inflammatory response is essential for
      eradicating pathogens. However, excessive inflammation can cause host tissue
      damage. Therefore, expression of IL-8 must be tightly regulated. We previously
      reported that NTHi induces IL-8 expression in an ERK-dependent manner. We also
      have shown that the deubiquitinase cylindromatosis (CYLD) suppresses NTHi-induced
      inflammation. However, the underlying molecular mechanism of how CYLD negatively
      regulates ERK-mediated IL-8 production is largely unknown. Here, we examine both
      human lung epithelial A549 cells and lung of Cyld-/- mice to show that CYLD
      specifically targets the activation of ERK. Interestingly, CYLD enhances NTHi
      induced upregulation of another negative regulator, MAP Kinase Phosphatase-1 (MKP
      1), which, in turn, leads to reduced ERK activation and subsequent suppression of
      IL-8. Taken together, the CYLD suppression of ERK-dependent IL-8 via MKP-1 may
      bring novel insights into the tight regulation of inflammatory responses and also
      lead to innovative therapeutic strategies for controlling these responses by
      targeting key negative regulators of inflammation. 

PMID- 25389770
TI  - Facial masculinity: how the choice of measurement method enables to detect its
      influence on behaviour.
AB  - Recent research has explored the relationship between facial masculinity, human
      male behaviour and males' perceived features (i.e. attractiveness). The methods
      of measurement of facial masculinity employed in the literature are quite
      diverse. In the present paper, we use several methods of measuring facial
      masculinity to study the effect of this feature on risk attitudes and
      trustworthiness. We employ two strategic interactions to measure these two
      traits, a first-price auction and a trust game. We find that facial width-to
      height ratio is the best predictor of trustworthiness, and that measures of
      masculinity which use Geometric Morphometrics are the best suited to link
      masculinity and bidding behaviour. However, we observe that the link between
      masculinity and bidding in the first-price auction might be driven by
      competitiveness and not by risk aversion only. Finally, we test the relationship
      between facial measures of masculinity and perceived masculinity. As a
      conclusion, we suggest that researchers in the field should measure masculinity
      using one of these methods in order to obtain comparable results. We also
      encourage researchers to revise the existing literature on this topic following
      these measurement methods. 

PMID- 25389771
TI  - Percutaneous resolution of lumbar facet joint cysts as an alternative treatment
      to surgery: a meta-analysis.
AB  - PURPOSE: A comprehensive review of the literature in order to analyze data about
      the success rate of percutaneous resolution of the lumbar facet joint cysts as a
      conservative management strategy. METHODS: A systematic search for relevant
      articles published during 1980 to May 2014 was performed in several electronic
      databases by using the specific MeSH terms and keywords. Most relevant data was
      captured and pooled for the meta-analysis to achieve overall effect size of
      treatment along with 95% confidence intervals. RESULTS: 29 studies were included
      in the meta-analysis. Follow-up duration as mean +/- sd (range) was 16+/-10.2 (5
      days to 5.7 years). Overall the satisfactory results (after short- or long-term
      follow-up) were achieved in 55.8 [49.5, 62.08] % (pooled mean and 95% CI) of the
      544 patients subjected to percutaneous lumbar facet joint cyst resolution
      procedures. 38.67 [33.3, 43.95] % of this population underwent surgery
      subsequently to achieve durable relief. There existed no linear relationship
      between the increasing average duration of follow-up period of individual studies
      and percent satisfaction from the percutaneous resolutions procedure. CONCLUSION:
      Results shows that the percutaneous cyst resolution procedures have potential to
      be an alternative to surgical interventions but identification of suitable
      subjects requires further research.

PMID- 25389772
TI  - Copper-catalyzed oxidative dehydrogenative carboxylation of unactivated alkanes
      to allylic esters via alkenes.
AB  - We report copper-catalyzed oxidative dehydrogenative carboxylation (ODC) of
      unactivated alkanes with various substituted benzoic acids to produce the
      corresponding allylic esters. Spectroscopic studies (EPR, UV-vis) revealed that
      the resting state of the catalyst is [(BPI)Cu(O2CPh)] (1-O2CPh), formed from
      [(BPI)Cu(PPh3)2], oxidant, and benzoic acid. Catalytic and stoichiometric
      reactions of 1-O2CPh with alkyl radicals and radical probes imply that C-H bond
      cleavage occurs by a tert-butoxy radical. In addition, the deuterium kinetic
      isotope effect from reactions of cyclohexane and d12-cyclohexane in separate
      vessels showed that the turnover-limiting step for the ODC of cyclohexane is C-H
      bond cleavage. To understand the origin of the difference in products formed from
      copper-catalyzed amidation and copper-catalyzed ODC, reactions of an alkyl
      radical with a series of copper-carboxylate, copper-amidate, and copper-imidate
      complexes were performed. The results of competition experiments revealed that
      the relative rate of reaction of alkyl radicals with the copper complexes follows
      the trend Cu(II)-amidate > Cu(II)-imidate > Cu(II)-benzoate. Consistent with this
      trend, Cu(II)-amidates and Cu(II)-benzoates containing more electron-rich aryl
      groups on the benzamidate and benzoate react faster with the alkyl radical than
      do those with more electron-poor aryl groups on these ligands to produce the
      corresponding products. These data on the ODC of cyclohexane led to preliminary
      investigation of copper-catalyzed oxidative dehydrogenative amination of
      cyclohexane to generate a mixture of N-alkyl and N-allylic products. 

PMID- 25389773
TI  - First molecular data and the phylogenetic position of the millipede-like
      centipede Edentistoma octosulcatum Tomosvary, 1882 (Chilopoda: Scolopendromorpha:
      Scolopendridae).
AB  - Edentistoma octosulcatum Tomosvary, 1882, is a rare, superficially millipede-like
      centipede known only from Borneo and the Philippines. It is unique within the
      order Scolopendromorpha for its slow gait, robust tergites, and highly modified
      gizzard and mandible morphology. Not much is known about the biology of the
      species but it has been speculated to be arboreal with a possibly vegetarian
      diet. Until now its phylogenetic position within the subfamily Otostigminae has
      been based only on morphological characters, being variably ranked as a monotypic
      tribe (Arrhabdotini) or classified with the Southeast Asian genus Sterropristes
      Attems, 1934. The first molecular data for E. octosulcatum sourced from a newly
      collected specimen from Sarawak were analysed with and without morphology.
      Parsimony analysis of 122 morphological characters together with two nuclear and
      two mitochondrial loci resolves Edentistoma as sister group to three Indo
      Australian species of Rhysida, this clade in turn grouping with Ethmostigmus,
      whereas maximum likelihood and parsimony analyses of the molecular data on their
      own ally Edentistoma with species of Otostigmus. A position of Edentistoma within
      Otostigmini (rather than being its sister group as predicted by the Arrhabdotini
      hypothesis) is consistently retrieved under different analytical conditions, but
      support values within the subfamily remain low for most nodes. The species
      exhibits strong pushing behaviour, suggestive of burrowing habits. Evidence
      against a suggested vegetarian diet is provided by observation of E. octosulcatum
      feeding on millipedes in the genus Trachelomegalus. 

PMID- 25389774
TI  - Potent anti-cancer effect of 3'-hydroxypterostilbene in human colon xenograft
      tumors.
AB  - Here we report that 3'-hydroxypterostilbene (HPSB), a natural pterostilbene
      analogue, was more potent than pterostilbene against the growth of human cancer
      cells (COLO 205, HCT-116, and HT-29) with measured IC50 values of 9.0, 40.2, and
      70.9 uM, respectively. We found that HPSB effectively inhibited the growth of
      human colon cancer cells by inducing apoptosis and autophagy. Autophagy occurred
      at an early stage and was observed through the formation of acidic vesicular
      organelles and microtubule-associated protein 1 light chain 3-II production. At
      the molecular levels, the results from western blot analysis showed that HPSB
      significantly down-regulated phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen
      activated protein kinases (MAPKs) signalings including decreased the
      phosphorylation of mammalian target of rapamycin (mTOR). Significant therapeutic
      effects were demonstrated in vivo by treating nude mice bearing COLO 205 tumor
      xenografts with HPSB (10 mg/kg i.p.). These inhibitory effects were accompanied
      by mechanistic down-regulation of the protein levels of cyclooxygenase-2 (COX-2),
      matrix metallopeptidase-9 (MMP-9), vascular endothelial growth factor (VEGF), and
      cyclin D1, as well as by the induction of apoptosis in colon tumors. Our findings
      suggest that HPSB could serve as a novel promising agent for colon cancer
      treatment. 

PMID- 25389775
TI  - Chronic glucocorticoid exposure-induced epididymal adiposity is associated with
      mitochondrial dysfunction in white adipose tissue of male C57BL/6J mice.
AB  - Prolonged and excessive glucocorticoids (GC) exposure resulted from Cushing's
      syndrome or GC therapy develops central obesity. Moreover, mitochondria are
      crucial in adipose energy homeostasis. Thus, we tested the hypothesis that
      mitochondrial dysfunction may contribute to chronic GC exposure-induced
      epididymal adiposity in the present study. A total of thirty-six 5-week-old male
      C57BL/6J mice (~20 g) were administrated with 100 ug/ml corticosterone (CORT) or
      vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly
      decreased body weight without altering food and water intake in mice. The
      epididymal fat accumulation was increased, but adipocyte size was decreased by
      CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth
      factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT
      increased plasma levels of triacylglycerols and nonesterified fatty acids, and up
      regulated the expression of both lipolytic and lipogenic genes as determined by
      real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and
      oxidative function in epididymal WAT. The reactive oxygen species production was
      increased and the activities of anti-oxidative enzymes were reduced by CORT
      treatment as well. Taken together, these findings reveal that chronic CORT
      administration-induced epididymal adiposity is, at least in part, associated with
      mitochondrial dysfunction in mouse epididymal white adipose tissue. 

PMID- 25389776
TI  - Cross-talk between ciliary epithelium and trabecular meshwork cells in-vitro: a
      new insight into glaucoma.
AB  - PURPOSE: It is assumed that the non-pigmented ciliary epithelium plays a role in
      regulating intraocular pressure via its neuroendocrine activities. To test this
      hypothesis, we investigated the effect on a human trabecular meshwork (TM) cell
      line (NTM) of co-culture with a human non-pigmented ciliary epithelium cell line
      (ODM-2). METHODS: The cellular cross-talk between ODM-2 and NTM cells was studied
      in a co-culture system in which the two cell types were co-cultured for 5 to 60
      min or 2, 4 and 8h and then removed from the co-culture and analyzed. Analyses of
      the ERK and p38 mitogen-activated protein kinase (MAPK) pathways and of the
      activity of TM phosphatases and matrix metalloproteins (MMPs) were performed.
      Acid and alkaline phosphatase activity was determined by the DiFMUP (6, 8
      difluoro-4-methylumbelliferyl phosphate) assay. MMP levels were determined by
      gelatin zymography. RESULTS: Exposure of NTM cells to ODM-2 cells led to the
      activation of the MAPK signal transduction pathways in NTM cells within 5 min of
      co-culture. Phosphorylation of ERK1/ERK2 and p38 peaked at 10 and 15 min and then
      decreased over time. Interaction between ODM-2 and NTM cells promoted the
      expression of MMP-9 in the NTM cells after 4h of co-culture. CONCLUSIONS: Our
      findings provide support for the hypothesis that crosstalk does indeed take place
      between ODM-2 and NTM cells. Future studies should be designed to determine the
      relationship between the MMP system, MAPK kinases and phosphatases. Manipulation
      of these signaling molecules and the related NTM signal transduction pathways may
      provide targets for developing improved treatments for glaucoma.

PMID- 25389777
TI  - Multi-country analysis of treatment costs for HIV/AIDS (MATCH): facility-level
      ART unit cost analysis in Ethiopia, Malawi, Rwanda, South Africa and Zambia.
AB  - BACKGROUND: Today's uncertain HIV funding landscape threatens to slow progress
      towards treatment goals. Understanding the costs of antiretroviral therapy (ART)
      will be essential for governments to make informed policy decisions about the
      pace of scale-up under the 2013 WHO HIV Treatment Guidelines, which increase the
      number of people eligible for treatment from 17.6 million to 28.6 million. The
      study presented here is one of the largest of its kind and the first to describe
      the facility-level cost of ART in a random sample of facilities in Ethiopia,
      Malawi, Rwanda, South Africa and Zambia. METHODS & FINDINGS: In 2010-2011,
      comprehensive data on one year of facility-level ART costs and patient outcomes
      were collected from 161 facilities, selected using stratified random sampling.
      Overall, facility-level ART costs were significantly lower than expected in four
      of the five countries, with a simple average of $208 per patient-year (ppy)
      across Ethiopia, Malawi, Rwanda and Zambia. Costs were higher in South Africa, at
      $682 ppy. This included medications, laboratory services, direct and indirect
      personnel, patient support, equipment and administrative services. Facilities
      demonstrated the ability to retain patients alive and on treatment at these
      costs, although outcomes for established patients (2-8% annual loss to follow-up
      or death) were better than outcomes for new patients in their first year of ART
      (77-95% alive and on treatment). CONCLUSIONS: This study illustrated that the
      facility-level costs of ART are lower than previously understood in these five
      countries. While limitations must be considered, and costs will vary across
      countries, this suggests that expanded treatment coverage may be affordable.
      Further research is needed to understand investment costs of treatment scale-up,
      non-facility costs and opportunities for more efficient resource allocation.

PMID- 25389779
TI  - Performance of two HCV RNA assays during protease inhibitor-based triple therapy
      in patients with advanced liver fibrosis and cirrhosis.
AB  - INTRODUCTION: On-treatment HCV RNA measurements are crucial for the prediction of
      a sustained virological response (SVR) and to determine treatment futility during
      protease inhibitor-based triple therapies. In patients with advanced liver
      disease an accurate risk/benefit calculation based on reliable HCV RNA results
      can reduce the number of adverse events. However, the different available HCV RNA
      assays vary in their diagnostic performance. AIM: To investigate the clinical
      relevance of concordant and discordant results of two HCV RNA assays during
      triple therapy with boceprevir and telaprevir in patients with advanced liver
      fibrosis/cirrhosis. METHODS: We collected on-treatment samples of 191 patients
      with advanced liver fibrosis/cirrhosis treated at four European centers for
      testing with the Abbott RealTime (ART) and COBAS AmpliPrep/COBAS TaqMan HCV v2.0
      (CTM) assays. RESULTS: Discordant test results for HCV RNA detectability were
      observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on-treatment. The
      ART detected HCV RNA in 41% of week 4 samples tested negative by the CTM.
      However, the positive predictive value of an undetectable week 4 result for SVR
      was similar for both assays (80% and 82%). Discordance was also found for
      application of stopping rules. In 27% of patients who met stopping rules by CTM
      the ART measured levels below the respective cut-offs of 100 and 1000 IU/ml,
      respectively, which would have resulted in treatment continuation. In contrast,
      in nine patients with negative HCV RNA by CTM at week 24 treatment would have
      been discontinued due to detectable residual HCV RNA by the ART assay.
      Importantly, only 4 of these patients failed to achieve SVR. CONCLUSION:
      Application of stopping rules determined in approval studies by one assay to
      other HCV RNA assays in clinical practice may lead to over and undertreatment in
      a significant number of patients undergoing protease inhibitor-based triple
      therapy.

PMID- 25389780
TI  - Comparative analysis of human gammaD-crystallin aggregation under physiological
      and low pH conditions.
AB  - Cataract, a major cause of visual impairment worldwide, is the opacification of
      the eye's crystalline lens due to aggregation of the crystallin proteins. The
      research reported here is aimed at investigating the aggregating behavior of
      gamma-crystallin proteins in various incubation conditions. Thioflavin T binding
      assay, circular dichroism spectroscopy, 1-anilinonaphthalene-8-sulfonic acid
      fluorescence spectroscopy, intrinsic (tryptophan) fluorescence spectroscopy,
      light scattering, and electron microscopy were used for structural
      characterization. Molecular dynamics simulations and bioinformatics prediction
      were performed to gain insights into the gammaD-crystallin mechanisms of
      fibrillogenesis. We first demonstrated that, except at pH 7.0 and 37 degrees C,
      the aggregation of gammaD-crystallin was observed to be augmented upon
      incubation, as revealed by turbidity measurements. Next, the types of aggregates
      (fibrillar or non-fibrillar aggregates) formed under different incubation
      conditions were identified. We found that, while a variety of non-fibrillar,
      granular species were detected in the sample incubated under pH 7.0, the
      fibrillogenesis of human gammaD-crystallin could be induced by acidic pH (pH
      2.0). In addition, circular dichroism spectroscopy, 1-anilinonaphthalene-8
      sulfonic acid fluorescence spectroscopy, and intrinsic fluorescence spectroscopy
      were used to characterize the structural and conformational features in different
      incubation conditions. Our results suggested that incubation under acidic
      condition led to a considerable change in the secondary structure and an
      enhancement in solvent-exposure of the hydrophobic regions of human gammaD
      crystallin. Finally, molecular dynamics simulations and bioinformatics prediction
      were performed to better explain the differences between the structures and/or
      conformations of the human gammaD-crystallin samples and to reveal potential key
      protein region involved in the varied aggregation behavior. Bioinformatics
      analyses revealed that the initiation of amyloid formation of human gammaD
      crystallin may be associated with a region within the C-terminal domain. We
      believe the results from this research may contribute to a better understanding
      of the possible mechanisms underlying the pathogenesis of senile nuclear
      cataract. 

PMID- 25389782
TI  - Postoperative Staphylococcus aureus infections in Medicare beneficiaries.
AB  - Staphylococcus aureus (S. aureus) infections are important because of their
      increasing frequency, resistance to antibiotics, and high associated rates of
      disabilities and deaths. We examined the incidence and correlates of S. aureus
      infections following 219,958 major surgical procedures in a 5% random sample of
      fee-for-service Medicare beneficiaries from 2004-2007. Of these surgical
      patients, 0.3% had S. aureus infections during the hospitalizations when index
      surgical procedures were performed; and 1.7% and 2.3%, respectively, were
      hospitalized with infections within 60 days or 180 days following admissions for
      index surgeries. S. aureus infections occurred within 180 days in 1.9% of
      patients following coronary artery bypass graft surgery, 2.3% following hip
      surgery, and 5.9% following gastric or esophageal surgery. Of patients first
      hospitalized with any major infection reported during the first 180 days after
      index surgery, 15% of infections were due to S. aureus, 18% to other documented
      organisms, and no specific organism was reported on claim forms in 67%. Patient
      level predictors of S. aureus infections included transfer from skilled nursing
      facilities or chronic hospitals and comorbid conditions (e.g., diabetes,
      congestive heart failure, chronic obstructive pulmonary disease, and chronic
      renal disease). In a logarithmic regression, elective index admissions with S.
      aureus infection stayed 130% longer than comparable patients without that
      infection. Within 180 days of the index surgery, 23.9% of patients with S. aureus
      infection and 10.6% of patients without this infection had died. In a
      multivariate logistic regression of death within 180 days of admission for the
      index surgery with adjustment for demographics, co-morbidities, and other risks,
      S. aureus was associated with a 42% excess risk of death. Due to incomplete
      documentation of organisms in Medicare claims, these statistics may underestimate
      the magnitude of S. aureus infection. Nevertheless, this study generated a higher
      rate of S. aureus infections than previous studies. 

PMID- 25389783
TI  - The Myotonometer: Not a Valid Measurement Tool for Active Hamstring
      Musculotendinous Stiffness.
AB  - CONTEXT: Hamstring musculotendinous stiffness (MTS) is associated with lower
      extremity injury risk (ie, hamstring strain, anterior cruciate ligament injury)
      and is commonly assessed using the damped oscillatory technique. However, despite
      a preponderance of studies that measure MTS reliably in laboratory settings,
      there are no valid clinical measurement tools. A valid clinical measurement
      technique is needed to assess MTS and permit identification of individuals at
      heightened risk of injury and track rehabilitation progress. OBJECTIVE: To
      determine the validity and reliability of the Myotonometer for measuring active
      hamstring MTS. DESIGN: Descriptive laboratory study. SETTING: Laboratory.
      PARTICIPANTS: 33 healthy participants (15 men, age 21.33 +/- 2.94 y, height
      172.03 +/- 16.36 cm, mass 74.21 +/- 16.36 kg). MAIN OUTCOME MEASURES: Hamstring
      MTS was assessed using the damped oscillatory technique and the Myotonometer.
      Intraclass correlations were used to determine the intrasession, intersession,
      and interrater reliability of the Myotonometer. Criterion validity was assessed
      via Pearson product-moment correlation between MTS measures obtained from the
      Myotonometer and from the damped oscillatory technique. RESULTS: The Myotonometer
      demonstrated good intrasession (ICC3,1 = .807) and interrater reliability (ICC2,k
      = .830) and moderate intersession reliability (ICC2,k = .693). However, it did
      not provide a valid measurement of MTS compared with the damped oscillatory
      technique (r = .346, P = .061). CONCLUSIONS: The Myotonometer does not provide a
      valid measure of active hamstring MTS. Although the Myotonometer does not measure
      active MTS, it possesses good reliability and portability and could be used
      clinically to measure tissue compliance, muscle tone, or spasticity associated
      with multiple musculoskeletal disorders. Future research should focus on portable
      and clinically applicable tools to measure active hamstring MTS in efforts to
      prevent and monitor injuries.

PMID- 25389781
TI  - FABP7 and HMGCS2 are novel protein markers for apocrine differentiation
      categorizing apocrine carcinoma of the breast.
AB  - Apocrine carcinoma of the breast is a distinctive malignancy with unique
      morphological and molecular features, generally characterized by being negative
      for estrogen and progesterone receptors, and thus not electable for endocrine
      therapy. Despite the fact that they are morphologically distinct from other
      breast lesions, no standard molecular criteria are currently available for their
      diagnosis. Using gel-based proteomics in combination with mass spectrometry and
      immunohistochemistry we have identified two novel markers, HMGCS2 and FABP7 that
      categorize the entire breast apocrine differentiation spectrum from benign
      metaplasia and cysts to invasive stages. Expression of HMGCS2 and FABP7 is
      strongly associated with apocrine differentiation; their expression is retained
      by most invasive apocrine carcinomas (IAC) showing positive immunoreactivity in
      100% and 78% of apocrine carcinomas, respectively, as compared to non-apocrine
      tumors (16.7% and 6.8%). The nuclear localization of FABP7 in tumor cells was
      shown to be associated with more aggressive stages of apocrine carcinomas. In
      addition, when added to the panel of apocrine biomarkers previously reported by
      our group: 15-PGDH, HMGCR and ACSM1, together they provide a signature that may
      represent a golden molecular standard for defining the apocrine phenotype in the
      breast. Moreover, we show that combining HMGCS2 to the steroidal profile
      (HMGCS2+/Androgen Receptor (AR)+/Estrogen Receptor(ER)-/Progesteron Receptor (PR)
      identifies IACs with a greater sensitivity (79%) as compared with the steroidal
      profile (AR+/ER-/PR-) alone (54%). We have also presented a detailed
      immunohistochemical analysis of breast apocrine lesions with a panel of
      antibodies against proteins which correspond to 10 genes selected from published
      transcriptomic signatures that currently characterize molecular apocrine subtype
      and shown that except for melanophilin that is overexpressed in benign apocrine
      lesions, these proteins were not specific for morphological apocrine
      differentiation in breast. 

PMID- 25389784
TI  - Sensitivity and specificity of hypopnoea detection using nasal pressure in the
      presence of a nasal expiratory resistive device (Provent(r)).
AB  - Nasal expiratory resistive valves (Provent((r))) have been proposed as novel
      therapy for obstructive sleep apnea. We compared pressure measurements from a
      standard nasal pressure catheter used to assess nasal airflow during sleep with
      those from nasal expiratory resistive device with attached proprietary nasal
      pressure cannula. Nasal pressure cannula or Provent((r)) + proprietary nasal
      pressure cannula were attached to a bench model of human anterior nares and nasal
      passages, and pressure measured (P). Respiratory airflows generated by a subject
      breathing were applied to rear of model and airflow (V) measured via
      pneumotachograph. Airflow amplitude (DeltaV) was plotted against pressure
      amplitude (DeltaP). Hypopnoea detection (<50% DeltaV) sensitivity and specificity
      was tested by expressing DeltaP in terms of two reference breaths: reference
      breath 1, DeltaV 0.55 L s(-1) = 100%; and reference breath 2, DeltaV 0.45 L s(-1)
      = 100%. DeltaP/DeltaV relationships were linear for DeltaV <= 0.55 L s(-1);
      DeltaP = 0.37DeltaV + 0.16 (nasal pressure cannula), DeltaP = 2.7DeltaV + 0.12
      (Provent((r)) + proprietary nasal pressure cannula); both R(2) > 0.65, p <
      0.0001; p < 0.0001 for between slope difference). For nasal pressure cannula,
      specificity of hypopnoea detection differed between reference breaths one and two
      (80.2% and 40.0%, respectively), and Provent((r)) + proprietary nasal pressure
      cannula (30.3% and 74.2%, respectively). Quantification of airflow obstruction in
      the presence of Provent((r)) + proprietary nasal pressure cannula is greatly
      influenced by the reference breath chosen to determine a reduction in nasal
      airflow. Reported variability in therapeutic response to nasal expiratory
      resistive devices may relate to differences in measurement technique specificity
      used to quantify the severity of sleep disordered breathing.

PMID- 25389788
TI  - Arsenicosis: the greatest public health disaster in history.

PMID- 25389789
TI  - On trichotillomania and its hairy history.

PMID- 25389790
TI  - First look: Google Glass in dermatology, Mohs surgery, and surgical
      reconstruction.

PMID- 25389791
TI  - Chemical depilatories in ancient Rome: the torpedo formula.

PMID- 25389792
TI  - Joe Roth: the star quarterback who played despite melanoma.

PMID- 25389793
TI  - Leishmaniasis: a disease with many names.

PMID- 25389794
TI  - Binding of the trichodysplasia spinulosa-associated polyomavirus small T antigen
      to protein phosphatase 2A: elucidation of a potential pathogenic mechanism in a
      rare skin disease.

PMID- 25389795
TI  - Gadolinium-associated plaques: a new, distinctive clinical entity.
AB  - IMPORTANCE: A new condition, gadolinium-associated plaques (GAP), is reported in
      2 patients. It is related to a particular type of gadolinium (gadodiamide) used
      for contrast-enhanced radiologic studies. OBSERVATIONS: Erythematous plaques, 0.5
      to 2.5 cm in diameter, were pruritic in one case and asymptomatic in a second
      case. Findings from the histopathologic examination revealed eosinophilic,
      collagenous, round or ovoid bodies (sclerotic bodies) in various stages of
      calcification. Previously, these sclerotic bodies were thought to be
      pathognomonic for nephrogenic systemic fibrosis (NSF) in the setting of chronic
      renal disease with associated gadolinium exposure. Neither patient had NSF, while
      only 1 of these patients had renal disease. The patient who did not have renal
      disease received high doses of gadolinium. CONCLUSIONS AND RELEVANCE: Physicians
      should be aware that GAP can occur without NSF or renal disease and is associated
      with the use of radiologic dyes. Sclerotic bodies have been reported only in
      association with gadolinium exposure (eg, gadodiamide) either in the sclerotic
      skin in NSF or in GAP.

PMID- 25389796
TI  - Molecular adhesion at clay nanocomposite interfaces depends on counterion
      hydration-molecular dynamics simulation of montmorillonite/xyloglucan.
AB  - Nacre-mimetic clay/polymer nanocomposites with clay platelet orientation parallel
      to the film surface show interesting gas barrier and mechanical properties. In
      moist conditions, interfacial adhesion is lowered and mechanical properties are
      reduced. Molecular dynamic simulations (MD) have been performed to investigate
      the effects of counterions on molecular adhesion at montmorillonite clay (Mnt)
      xyloglucan (XG) interfaces. We focus on the role of monovalent cations K(+),
      Na(+), and Li(+) and the divalent cation Ca(2+) for mediating and stabilizing the
      Mnt/XG complex formation. The conformation of adsorbed XG is strongly influenced
      by the choice of counterion and so is the simulated work of adhesion. Free energy
      profiles that are used to estimate molecular adhesion show stronger interaction
      between XG and clay in the monovalent cation system than in divalent cation
      system, following a decreasing order of K-Mnt, Na-Mnt, Li-Mnt, and Ca-Mnt. The
      Mnt clay hydrates differently in the presence of different counterions, leading
      to a chemical potential of water that is highest in the case of K-Mnt, followed
      by Na-Mnt and Li-Mnt, and lowest in the case of Ca-Mnt. This means that water is
      most easily displaced from the interface in the case of K-Mnt, which contributes
      to the relatively high work of adhesion. In all systems, the penalty of replacing
      polymer with water at the interface gives a positive contribution to the work of
      adhesion of between 19 and 35%. Our work confirms the important role of
      counterions in mediating the adsorption of biopolymer XG to Mnt clays and
      predicts potassium or sodium as the best choice of counterions for a Mnt-based
      biocomposite design. 

PMID- 25389797
TI  - Computational assessment of non-heteroatom-stabilized carbene complexes
      reactivity: formation of oxazine derivatives.
AB  - A complete DFT-level mechanism elucidation of the two-step reaction of non
      heteroatom-stabilized carbenes with imines, followed by addition of alkynes to
      yield oxazine derivatives, is presented. These compounds show different
      reactivity than the equivalent Fischer carbene complexes. A rationale of the
      experimental outcome is presented together with some suggestion for increasing
      the scope of the reaction, with special attention to the solvent effects in the
      regioselectivity. 

PMID- 25389798
TI  - Conformational behavior of flavin adenine dinucleotide: conserved stereochemistry
      in bound and free states.
AB  - Metabolic enzymes utilize the cofactor flavin adenine dinucleotide (FAD) to
      catalyze essential biochemical reactions. Because these enzymes have been
      implicated in disease pathways, it will be necessary to target them via FAD-based
      structural analogues that can either activate/inhibit the enzymatic activity. To
      achieve this, it is important to explore the conformational space of FAD in the
      enzyme-bound and free states. Herein, we analyze X-ray crystallographic data of
      the enzyme-bound FAD conformations and sample conformations of the molecule in
      explicit water by molecular dynamics (MD) simulations. Enzyme-bound FAD
      conformations segregate into five distinct groups based on dihedral angle
      principal component analysis (PCA). A notable feature in the bound FADs is that
      the adenine base and isoalloxazine ring are oppositely oriented relative to the
      pyrophosphate axis characterized by near trans hypothetical dihedral angle
      "deltaV" values. Not surprisingly, MD simulations in water show final compact but
      not perfectly stacked ring structures in FAD. Simulation data did not reveal
      noticeable changes in overall conformational dynamics of the dinucleotide in
      reduced and oxidized forms and in the presence and/or absence of ions. During
      unfolding-folding dynamics, the riboflavin moiety is more flexible than the
      adenosine monophosphate group in the molecule. Conversely, the isoalloxazine ring
      is more stable than the variable adenine base. The pyrophosphate group depicts an
      unusually highly organized fluctuation illustrated by its dihedral angle
      distribution. Conformations sampled from enzymes and MD are quantified. The
      extent to which the protein shifts the distribution from the unbound state is
      discussed in terms of prevalent FAD shapes and dihedral angle population. 

PMID- 25389799
TI  - Epitaxial growth of a single-domain hexagonal boron nitride monolayer.
AB  - We investigate the structure of epitaxially grown hexagonal boron nitride (h-BN)
      on Ir(111) by chemical vapor deposition of borazine. Using photoelectron
      diffraction spectroscopy, we unambiguously show that a single-domain h-BN
      monolayer can be synthesized by a cyclic dose of high-purity borazine onto the
      metal substrate at room temperature followed by annealing at T=1270 K, this
      method giving rise to a diffraction pattern with 3-fold symmetry. In contrast,
      high-temperature borazine deposition (T=1070 K) results in a h-BN monolayer
      formed by domains with opposite orientation and characterized by a 6-fold
      symmetric diffraction pattern. We identify the thermal energy and the binding
      energy difference between fcc and hcp seeds as key parameters in controlling the
      alignment of the growing h-BN clusters during the first stage of the growth, and
      we further propose structural models for the h-BN monolayer on the Ir(111)
      surface.

PMID- 25389800
TI  - Energy and exergy analyses of an integrated gasification combined cycle power
      plant with CO2 capture using hot potassium carbonate solvent.
AB  - Energy and exergy analyses were studied for an integrated gasification combined
      cycle (IGCC) power plant with CO2 capture using hot potassium carbonate solvent.
      The study focused on the combined impact of the CO conversion ratio in the water
      gas shift (WGS) unit and CO2 recovery rate on component exergy destruction, plant
      efficiency, and energy penalty for CO2 capture. A theoretical limit for the
      minimal efficiency penalty for CO2 capture was also provided. It was found that
      total plant exergy destruction increased almost linearly with CO2 recovery rate
      and CO conversion ratio at low CO conversion ratios, but the exergy destruction
      from the WGS unit and the whole plant increased sharply when the CO conversion
      ratio was higher than 98.5% at the design WGS conditions, leading to a
      significant decrease in plant efficiency and increase in efficiency penalty for
      CO2 capture. When carbon capture rate was over around 70%, via a combination of
      around 100% CO2 recovery rate and lower CO conversion ratios, the efficiency
      penalty for CO2 capture was reduced. The minimal efficiency penalty for CO2
      capture was estimated to be around 5.0 percentage points at design conditions in
      an IGCC plant with 90% carbon capture. Unlike the traditional aim of 100% CO
      conversion, it was recommended that extremely high CO conversion ratios should
      not be considered in order to decrease the energy penalty for CO2 capture and
      increase plant efficiency. 

PMID- 25389801
TI  - The liturgical cope of D. Teotonio of Braganza: material characterization of a
      16th century pluviale.
AB  - A 16th century liturgical cope belonging to D. Teotonio of Braganza (collection
      of the Museum of Evora, ME 172/1) was selected for a material study. The cope is
      made of a variety of materials that include two different types of metal threads,
      dyed silk yarns, and vegetable yarns used in the weft. Several samples from
      different points representing the different metal thread types and colored silk
      yarns were collected. Stereomicroscopy (optical microscopy) and scanning electron
      microscopy were used for morphological analysis of the textile fibers and
      evaluation of metal thread degradation products. Evaluation of mordants and metal
      thread composition was carried out by energy-dispersive X-ray spectroscopy.
      Liquid chromatography with diode array and mass spectrometry detection was used
      for dye identification, which allowed the determination of three different red
      dye sources and one yellow dye source in the colored silk yarns. Although
      different fabrics were used in the manufacturing of the cope, similarities
      identified in the characterization of the materials suggest that a single
      workshop was involved in its making. 

PMID- 25389803
TI  - Implementing early diagnosis and treatment: programmatic considerations.
AB  - PURPOSE OF REVIEW: To benefit very early treatment for an HIV cure, HIV infection
      must be diagnosed immediately after infection. We review potential strategies for
      expansion of HIV testing in preparation for a potential HIV cure in the distant
      future. RECENT FINDINGS: Very early antiretroviral therapy (ART) initiated during
      acute or early HIV infection may result in long-term viral control. Such
      strategies will require programmatic systems for very early diagnosis and very
      early ART. Yet, most HIV-infected individuals start treatment late and presumably
      are diagnosed late. Operational issues will have to address the treatment cascade
      much earlier starting from HIV testing, test result notification, posttest
      counseling, immunological and clinical assessment and ultimately starting
      treatment. Well designed implementation research studies are needed to determine
      effective interventions to diagnose HIV as early as during acute and early HIV
      infection. SUMMARY: Approaches for earlier HIV diagnosis and very early ART for a
      potential functional HIV cure remain elusive unless early HIV diagnosis can be
      radically expanded.

PMID- 25389802
TI  - Review: Influence of ART on HIV genetics.
AB  - PURPOSE OF REVIEW: HIV genetic diversity poses major challenges for the
      prevention, control, and cure of infection. Characterizing the diversity and
      evolution of HIV populations within the host provides insights into the
      mechanisms of HIV persistence during antiretroviral therapy (ART). This review
      describes the HIV diversity within patients, how it is affected by suppressive
      ART, and makes a case for early treatment after HIV infection. RECENT FINDINGS:
      HIV evolution is effectively halted by ART. However, cells that were infected
      prior to initiating therapy can proliferate to very high numbers both before and
      during treatment. Such clonal expansions result in the persistence of integrated
      proviruses despite therapy. These expanding proviruses have been shown to be a
      source for residual viremia during ART, and they may be a source for viral
      rebound after interrupting ART. SUMMARY: Plasma HIV RNA shows no evidence for
      evolution during ART, suggesting that HIV persistence is not driven by low-level,
      ongoing replication. The emergence of identical viral sequences observed in both
      HIV RNA and DNA is likely due to proliferation of infected cells. Early treatment
      restricts the viral population and reduces the number of variants that must be
      targeted for future therapeutic strategies.

PMID- 25389804
TI  - Impact of earlier combination antiretroviral therapy on outcomes in children.
AB  - PURPOSE OF REVIEW: Early initiation of combination antiretroviral therapy (ART)
      in infants below 12 weeks of age reduces morbidity and mortality. A recent report
      of transient HIV remission in a child beginning ART from the second day of life
      has focused attention on very early therapy in the first days of life. RECENT
      FINDINGS: In the randomized children with HIV, early antiretroviral limited ART
      beginning at a median of 7.4 weeks of age lowered mortality and disease
      progression significantly compared with deferred ART beginning at a median of 21
      weeks on study. In high-burden settings, infants initiating ART appear sicker
      than in children with HIV early antiretroviral and start at a later age. Many
      could be diagnosed on the first day of life. There are still programmatic
      obstacles to early diagnosis and initiation of ART in high-burden settings. There
      is growing but insufficient information on ART dosages in newborn infants.
      SUMMARY: There is now increased focus on initiating ART as postexposure
      prophylaxis in newborn infants at high risk of vertical transmission in the hope
      of limiting morbidity and dissemination of the virus.

PMID- 25389807
TI  - A cure for HIV: what will it take?

PMID- 25389805
TI  - Preserving HIV-specific T cell responses: does timing of antiretroviral therapy
      help?
AB  - PURPOSE OF REVIEW: HIV-specific T cell responses are likely to have an important
      role in HIV cure strategies that aim for long-lasting viral control without
      antiretroviral therapy (ART). An important issue in enhancing virus-specific T
      cell responses is whether timing of ART can influence their magnitude and
      breadth. RECENT FINDINGS: Early ART is associated with lower T cell activation,
      preservation of T cell numbers, smaller DNA and RNA reservoir size, and, in a
      single study (VISCONTI), control of plasma viremia after treatment interruption.
      The prevention of T cell destruction by early ART is associated with relatively
      low anti-HIV CD8+ T cell responses but stronger CD4+ T helper function. The
      relatively lower CD8+T cell response, which is presumably due to rapid lowering
      of HIV antigen burden after early ART, appears sufficient to control residual
      viral replication as well as viral rebound upon treatment interruption. SUMMARY:
      Available evidence of starting ART during acute or early HIV infection has shown
      benefit in both virologic and immunologic parameters despite the lower HIV
      specific CD8+ T cell responses observed. Encouraging as this is, more extensive
      data are necessary to evaluate its role in combination with immunotherapeutic and
      latency activation strategies that are being assessed in various HIV cure-related
      studies.

PMID- 25389808
TI  - The Development and Use of a Modified WHO Checklist for Use in Electroconvulsive
      Therapy.
AB  - The World Health Organization checklist is proven to reduce morbidity and
      mortality and is mandatory in operating theater settings, but not for
      electroconvulsive therapy (ECT) in the UK. We believe that such a checklist is
      especially relevant in an ECT setting because of the high turnover of short cases
      and for specific checks particularly pertinent to ECT patients. Our ECT team has
      developed a checklist with the headings Sign In, Psychiatric Concerns, Anesthetic
      Concerns, and Recovery, which we have found efficacious. We recommend that all
      centers offering ECT develop their own World Health Organization checklist to
      improve patient safety. 

PMID- 25389809
TI  - Use of electroconvulsive therapy in schizophrenia with Klippel-Feil syndrome.

PMID- 25389806
TI  - How can we better identify early HIV infections?
AB  - PURPOSE OF REVIEW: Detection of early HIV infections (EHIs), including acute HIV
      infection (AHI), is important for individual health, prevention of HIV
      transmission, and measurement of HIV incidence. We describe markers of EHI,
      diagnostic strategies for detecting these markers, and ways to incorporate these
      strategies into diagnostic and HIV incidence algorithms. RECENT FINDINGS: For
      individual diagnosis in the USA and Europe, laboratory-based diagnostic
      algorithms increasingly incorporate fourth-generation HIV antigen tests, allowing
      for earlier detection. In some sub-Saharan African settings, symptom-based
      screening is being explored to identify subsets of persons at high risk for AHI.
      Point-of-care diagnostics designed for AHI detection are in the pipeline and, if
      validated, represent an opportunity for real-time AHI diagnosis. At the
      population level, multiassay algorithms are promising new strategies for
      estimating HIV incidence on the basis of several assays applied to cross
      sectional samples. These algorithms can be developed to optimize performance, in
      addition to cost and logistical considerations. SUMMARY: There are important
      recent advances in detection of EHIs at the individual and population levels.
      Applying optimal combinations of tests in diagnostic and HIV incidence algorithms
      is urgently needed to support the multiple goals derived from enhanced detection
      and discrimination of EHIs.

PMID- 25389810
TI  - Familial bilateral macular aneurysmal telangiectasia.
AB  - BACKGROUND: Idiopathic macular aneurysmal telangiectasia or so-called Coats'
      disease is usually a unilateral retinal vascular abnormality in males. It has
      been rarely reported to occur bilaterally with and without associated
      abnormalities, and its occurrence in a familial setting is even rarer. PURPOSE:
      This is a report of a familial occurrence of bilateral macular aneurysmal
      telangiectasia or Coats' disease in a father and daughter. RESULTS: A 44-year-old
      woman and her father had bilateral macular angiopathy with macular
      telangiectasia, aneurysms, ischemia, and leakage, including lipid deposition. The
      clinical findings were confirmed with fluorescein angiography and optical
      coherence tomography. There was no history of systemic disease associated with a
      retinal vascular abnormality. CONCLUSION: To our knowledge, this is the first
      report of a familial occurrence of bilateral macular aneurysmal telangiectasia or
      Coats' disease in a daughter and father without associated systemic disease.

PMID- 25389811
TI  - Confocal (en face) optical coherence tomography in vascularized retinal pigment
      epithelium detachment.
AB  - PURPOSE: To describe the relationship between pigment epithelial detachment (PED)
      and choroidal neovascularization (CNV) by overlay of en face optical coherence
      tomography (OCT) and indocyanine green angiography/scanning laser ophthalmoscopy
      (SLO). METHODS: Observational case report of a 75-year-old patient with age
      related macular degeneration who presented with reduced vision and a vascularized
      PED-V scanned with an en face OCT ophthalmoscope. RESULTS: The OCT scan
      demonstrated the actual route of the CNV from the choroid to the subretinal space
      and a clearly delineated highly reflective area behind the vascularized PED and
      serous detachment; it also showed hyperreflectivity in the outer retina at the
      site of the lesion. CONCLUSIONS: En face OCT allows for better evaluation of
      intraretinal changes in patients with vascularized PED. In this case, OCT and SLO
      showed different morphologic changes in active lesions and may be helpful in
      identifying the site of occult CNV. This may have prognostic and therapeutic
      significance.

PMID- 25389812
TI  - 3d spectral optical coherence tomography documentation of a retinal vein
      occlusion associated with a pigment epithelial detachment.
AB  - PURPOSE: To describe a case of a pigment epithelial detachment (PED) that likely
      led to a branch retinal vein occlusion (BRVO). METHODS: Color photography,
      fluorescein angiography, and three-dimensional spectral optical coherence
      tomography (3D-spectral OCT) were performed. RESULTS: Fluorescein angiography
      identified a PED at the site of a BRVO, and 3D-spectral OCT illustrated
      compression and distortion of the overlying retina at the location of the venous
      obstruction. CONCLUSION: It is well known that retinal arterial disease can
      compress an underlying vein and lead to a BRVO. A theoretically possible, but
      previously unrecognized cause of a BRVO is compression of an overlying vein by an
      underlying PED. Our case reminds us to continue to explore local anatomical
      factors in addition to systemic factors in patients with venous occlusive
      disease.

PMID- 25389813
TI  - Resolution of retinal pigment epitheliitis-optical coherence tomography findings.
AB  - PURPOSE: To describe the morphologic appearance of the retina during the course
      of acute retinal pigment epitheliitis (ARPE) with optical coherence tomography
      (OCT). METHODS: Observational case report. RESULTS: OCT demonstrated an
      abnormality in the inner higher reflective line, which represents the outer and
      inner segments of the retinal photoreceptors at the fovea. Four months later, the
      tomographic appearance returned to normal. CONCLUSION: Photoreceptors segments
      are involved in the disease process of ARPE. OCT demonstrated the different
      stages in the resolution of ARPE.

PMID- 25389814
TI  - Residual bubble of oxane hd: a study by optical coherence tomography and fundus
      related perimetry.
AB  - PURPOSE: Oxane HD is a mixture of silicone oil and a mixed fluorinated and
      hydrocarbonated olefin. The authors report a complication of Oxane HD as internal
      tamponade after removal of all visible heavy silicone oil. METHODS: A 71-year-old
      man who underwent vitrectomy with Oxane HD presented with adherence of a residual
      bubble of Oxane HD in the macula after removal of all visible heavy silicone oil.
      In this patient OCT displayed an optical artifact due to the residual bubble, and
      fundus-related perimetry revealed a predominantly eccentric and relatively
      unstable fixation and very low macular sensitivity. RESULTS: After surgical
      removal of the residual bubble, metamorphopsia resolved, sensitivity improved as
      revealed by fundus-related perimetry, and fixation became predominantly central
      and more stable. CONCLUSION: The authors suggest a way to manage this rare
      complication of Oxane HD as internal tamponade after removal of all visible heavy
      silicone oil.

PMID- 25389815
TI  - Oct findings in torpedo maculopathy.
AB  - BACKGROUND: Torpedo maculopathy, also called solitary hypopigmented nevus, is a
      rare though benign disorder. To our knowledge, there are no previous optical
      coherence tomography (OCT) descriptions in the literature. METHODS: Results of
      ophthalmologic examinations (including retinography, OCT, and visual field
      testing) for 2 girls aged 12 years and 13 years throughout 5 years of follow-up
      were reviewed. RESULTS: In both cases, anterior and posterior segment evaluation
      was unremarkable except for the presence of a flat, fishtail-shaped,
      hypopigmented lesion temporal to the macula, pointing to the fovea. In case 1,
      OCT disclosed faint thinning of the retina above the lesion especially in the
      outer retina and hyperreflectivity of the retinal pigment epithelium (RPE)
      associated with a posterior hyperreflective signal deep in the choroids. In case
      2, OCT showed an atrophic retina with reduced thickness probably due to the
      absence of the photoreceptor layer. Shallow serous neurosensory detachment,
      increased RPE reflectivity, and higher penetration of light to the choroid were
      also evident. CONCLUSION: In both cases of torpedo maculopathy studied by OCT, we
      found a variable amount of retinal degeneration, and a serous retinal detachment
      was found in one case.

PMID- 25389816
TI  - COMBINED SCLERAL BUCKLING AND INTRAVITREAL PLASMIN INJECTION: A New Surgical
      Technique.
AB  - PURPOSE: To report a new surgical technique for repair of rhegmatogenous retinal
      detachments in children. METHODS: This study is an interventional case series.
      Combined scleral buckling and enzymatic vitrectomy by autologous plasmin was
      performed in three patients who presented with rhegmatogenous retinal detachment.
      Anatomic and functional outcomes as well as surgical complications were recorded.
      RESULTS: Following combined surgery, all patients achieved retinal reattachment.
      Two patients had recordable and improved vision. None of the patients developed
      surgical complications after at least 21 months of follow-up. CONCLUSION:
      Combined scleral buckling and enzymatic vitrectomy achieves retinal reattachment
      and functional improvement in selected pediatric patients with rhegmatogenous
      retinal detachment who require scleral buckling and vitrectomy.

PMID- 25389817
TI  - Giant pigment epithelial tear after scleral buckling for rhegmatogenous retinal
      detachment.
AB  - PURPOSE: To describe a patient with rhegmatogenous retinal detachment (RRD) who
      developed a giant tear of retinal pigment epithelium (RPE) after scleral
      buckling. PATIENT: A 64-year-old man with RRD underwent scleral buckling and
      cryoretinopexy on his right eye. RESULTS: A #506 silicone sponge was placed on
      the exit of the three vortex vein to seal retinal tears. On the 3 postoperative
      day, a choroidal detachment appeared, and on the 10 postoperative day, a large
      RPE developed at the posterior edge of the choroidal detachment. One month later,
      the entire retina was completely attached without any treatment. CONCLUSIONS:
      Ophthalmic surgeons should be aware that an RPE tear can be associated with
      choroidal detachment after scleral buckling.

PMID- 25389818
TI  - Elevated erythropoietin and vascular endothelial growth factor levels in an
      adolescent with retinal neovascularization from a chronic rhegmatogenous retinal
      detachment.
AB  - PURPOSE: To evaluate the role of erythropoietin and vascular endothelial growth
      factor (VEGF) in a patient with retinal neovascularization from a rhegmatogenous
      retinal detachment of long duration. METHODS: Fundus photography, fluorescein
      angiography, and vitreous analysis were performed. The vitreous concentrations of
      erythropoietin and VEGF were measured by enzyme-linked immunosorbent assays and
      compared with control levels. RESULTS: An adolescent with a history of mild
      retinopathy of prematurity presented with a retinal detachment found by routine
      examination. The patient had a rhegmatogenous retinal detachment with signs of
      chronicity and extensive retinal neovascularization. The patient's erythropoietin
      level was higher than those of patients with proliferative diabetic retinopathy.
      The patient's VEGF level was not as high as those of patients with proliferative
      diabetic retinopathy but was elevated compared with those of patients without
      neovascularization. CONCLUSION: Vitreous concentrations of erythropoietin and
      VEGF can be elevated in patients with neovascularization secondary to a
      rhegmatogenous retinal detachment of long duration.

PMID- 25389819
TI  - Delayed choroidal hemorrhage with concomitant subconjunctival hemorrhage after
      retinal detachment surgery.
AB  - BACKGROUND: Suprachoroidal hemorrhage is a known serious complication of all
      types of intraocular surgery and is associated with severe visual debility. Most
      cases of suprachoroidal hemorrhage occur intraoperatively. Suprachoroidal
      hemorrhage as a complication of vitrectomy has been described near the end of
      vitrectomy or on the first postoperative day. METHODS: This case report describes
      a patient presenting with a delayed suprachoroidal hemorrhage occurring 5 days
      after vitreoretinal surgery in association with subconjunctival hemorrhage.
      RESULTS AND CONCLUSION: To our knowledge, we report the first case of a delayed
      suprachoroidal hemorrhage associated with vitreoretinal surgery. With proper
      management, the outcome is not always unfavorable.

PMID- 25389820
TI  - Superior retinal detachment in an oil-filled eye with a colobomatous optic disc.
AB  - BACKGROUND: Optic disk pits are known as congenital cavitary defects associated
      with serous detachment of the retina; 75% of such cases do not resolve
      spontaneously, and surgical management is required. The use of gas or oil
      tamponade in these cases has been associated with detachment of the retina
      attributed to the passage of intravitreal gas or fluid via the disk pit and into
      the subretinal space. Prophylactic peripapillary laser retinopexy is therefore
      recommended peroperatively to create a barrier to fluid flow between the vitreous
      cavity and the subretinal space. METHODS: Case report. RESULTS: We report a case
      of optic nerve coloboma and serous macular detachment with redetachment of the
      retina that occurred many months after initial gas and then oil tamponade. The
      patient developed a superior retinal detachment containing oil in an oil-filled
      eye in the absence of retinal breaks. To our knowledge, superior retinal
      detachment containing oil in an oil-filled eye with an optic disk pit has not
      been described previously. CONCLUSION: This case raises an interesting discussion
      on both the pathophysiology of redetachment associated with optic disk pits and
      their management.

PMID- 25389821
TI  - Serous retinal detachment secondary to choroidal osteoma successfully treated
      with transpupillary thermotherapy.
AB  - PURPOSE: To report a case of serous retinal detachment (SRD) associated with
      choroidal osteoma successfully treated with transpupillary thermotherapy (TTT).
      METHODS: A 21-year-old woman presented with a 1-month history of blurred vision
      in the right eye. RESULTS: Visual acuity was 20/50 in the right eye and 20/20 in
      the left eye. Fundus examination of the right eye revealed a suprapapillary
      choroidal osteoma associated with SRD extending to the macula. Fluorescein
      angiography showed diffuse mottled hyperfluorescence of the tumor associated with
      a moderately leaking area at its inferior border within the area of SRD. There
      were neither obvious features of choroidal neovascularization nor typical focal
      retinal pigment epithelial leaks. TTT, applied to the leaking area in one session
      using an 810-nm diode laser, resulted in resolution of subretinal fluid and
      subsequent improvement in visual acuity to 20/25. CONCLUSION: TTT can be
      considered as treatment for patients with choroidal osteoma complicated by SRD.

PMID- 25389822
TI  - Postoperative giant retinal pseudotear.
AB  - PURPOSE: To describe a case of an unusual vitreous membrane simulating detachment
      of a giant retinal tear after previous surgical repair. PATIENT: A 52-year-old
      man underwent vitrectomy for repair of a giant retinal tear. Six weeks later, a
      prominent vitreous membrane simulating recurrent detachment of the giant retinal
      tear was noted. Fundus photography, fluorescein angiography, and optical
      coherence tomography were used to characterize the membrane and its relationship
      to the contiguous retina. RESULTS: Fluorescein angiography and optical coherence
      tomography confirmed avascularity of the lesion and presence of retinal vessels
      and retinal tissue extending anterior to the membrane without distortion. Follow
      up 8 months later demonstrated no progression, complete retinal attachment, and
      visual acuity of 20/20. CONCLUSIONS: Recognition of this condition is important
      to avoid unnecessary reoperation. Findings were consistent with a condensed
      hyaloidal membrane or organized postoperative fibrin membrane. The term "giant
      retinal pseudotear" is proposed.

PMID- 25389823
TI  - Charles bonnet syndrome associated with age-related macular degeneration.
AB  - PURPOSE: The visual hallucinations in Charles Bonnet syndrome (CBS) are most
      commonly attributed to release phenomena that arise due to a paucity of sensory
      input to visual association areas of the cerebral cortex (Cogan's sensory
      deprivation theory of visual hallucinations). The authors wished to gain further
      insight into this mechanism behind CBS by examining a patient who experienced
      reversible visual hallucinations. METHODS: The authors present a 77-year-old man
      with a history of severe age-related macular degeneration who experienced formed
      and moving visual hallucinations associated with CBS shortly after a retinal
      pigment epithelial detachment (RPED) in his right eye. His visual acuity had been
      reduced to 20/400 in the right eye. RESULTS: Visual acuity improved to 20/50 in
      the right eye after a series of Macugen injections led to RPED resolution as
      evidenced by optical coherence tomography and fluorescein angiography. The visual
      hallucinations abruptly ceased after this dramatic improvement in visual acuity.
      CONCLUSION: Reestablishment of high resolution visual input leads to a dramatic
      and almost immediate increase in the stimulus threshold of visual cortex cells as
      reflected by resolution of symptoms. The subthreshold signals that reach
      consciousness to produce visual hallucinations in CBS are thus immediately
      mitigated.

PMID- 25389824
TI  - Rate of microbiological contamination in vials of bevacizumab used for multiple
      intravitreal injections.
AB  - PURPOSE: A prospective pilot study was undertaken to determine the rate (if any)
      of microbiological contamination in vials of bevacizumab (Avastin; Genentech,
      Inc., South San Francisco, CA) being accessed for multiple intravitreal
      injections. METHODS: Twenty-one unfractionated, 100-mg (4 mL) vials of
      bevacizumab were used for 321 intravitreal injections. Each vial was accessed
      multiple times under sterile conditions. Upon completion of each vial, the
      residual contents were stored for a further 2 weeks before being sent for
      microbiological contamination studies. RESULTS: No evidence of microbiological
      contamination was detected in 21 vials sent for assessment. Of 321 intravitreal
      injections performed, none was associated with any sign of endophthalmitis.
      CONCLUSIONS: Using the same vial multiple times for intravitreal injections
      (stored for up to 4 weeks after opening) is a reasonable alternative to other
      methods of administering bevacizumab. Larger studies are required to determine
      the safety and efficacy of this practice.

PMID- 25389825
TI  - Functional and anatomical outcomes for intravitreal bevacizumab treatment of
      choroidal neovascularization in a patient with angioid streaks.
AB  - PURPOSE: To evaluate the visual and anatomical outcomes of intravitreal
      bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) treatment of
      choroidal neovascularization (CNV) in patients with angioid streaks (ASs).
      METHODS: A 44-year-old man with angioid streaks and CNV in both eyes (best
      corrected visual acuity: 20/400, right eye; 20/50, left eye) received
      intravitreal bevacizumab injections at monthly intervals. RESULTS: Best-corrected
      visual acuity in the right eye after 2 intravitreal injections of bevacizumab was
      20/70 and remained the same at the 6-month follow-up. Best-corrected visual
      acuity in the left eye after 3 intravitreal injections of bevacizumab was 20/25
      and remained the same at the 9-month follow-up. CONCLUSIONS: After intravitreal
      administration of bevacizumab, our patient had visual acuity improvement in both
      eyes that was associated with rapid and significant reduction in thickness,
      subretinal fluid, and size of subfoveal neovascularization secondary to ASs.
      Intravitreal bevacizumab treatment resulted in a meaningful and sustained vision
      gain after the 9-months follow-up.

PMID- 25389826
TI  - Intravitreal bevacizumab treatment of retinal telangiectasis complicated by
      subretinal neovascularization.
AB  - BACKGROUND: Idiopathic perifoveal telangiectasia (IPT) is a disorder
      characterized by focal parafoveal capillary dilatation of unknown cause.
      Photodynamic therapy (PDT) was reported to be efficacious in the treatment of
      subretinal neovascularization (SRN) associated with idiopathic juxtafoveal
      retinal telangiectasis. However, visual improvement is limited. METHODS: We
      describe the clinical, angiographic, and optical coherence tomography findings
      for a patient with IPT complicated with SRN and treated with PDT and bevacizumab.
      RESULTS: The patient underwent 2 sessions of PDT; however, metamorphopsia
      persisted, and visual acuity further decreased to 20/100 after the second PDT.
      Two injections of intravitreal bevacizumab (1.25 mg) were administered after PDT.
      Visual acuity increased dramatically from 20/100 to 20/25 after the injections.
      Four months after the second injection, there was no recurrence, and the patient
      was asymptomatic. CONCLUSION: Intravitreal bevacizumab treatment should be
      considered for patients with SRN associated with perifoveal telangiectasis,
      especially after insufficient therapeutic response to PDT.

PMID- 25389827
TI  - Intravitreal bevacizumab for treatment of peripapillary subretinal
      neovascularization.
AB  - PURPOSE: To describe the effects of intravitreal bevacizumab treatment for
      peripapillary subretinal neovascularization. METHOD: A patient with an idiopathic
      peripapillary subretinal neovascular membrane in the papillomacular bundle, which
      led to subretinal hard exudate deposits in the fovea and decreased visual acuity,
      was treated with a single intravitreal injection of 0.04 mL (1 mg) of
      bevacizumab. Main outcomes consisted of visual acuity, fluorescein (FA) and
      indocyanine green (ICG) angiography, and optical coherence tomography (OCT).
      RESULTS: One week after the treatment the patient had less blurred vision and
      metamorphopsia but visual acuity was unchanged. At the 1 month visit the visual
      acuity improved and reduced leakage of the membrane was shown by FA and ICG. OCT
      demonstrated a reduction of the macular edema. At 14 months follow-up visit the
      membrane was not detectable with FA and ICG and only isolated remnants of the
      exudates were still present. OCT showed resolution of the macular edema and a
      residual hard exudate localized nasally to the fovea. CONCLUSIONS: Treatment of
      peripapillary subretinal neovascular membrane with a single intravitreal
      injection of bevacizumab was effective and well-tolerated without recurrence of
      the neovascularization after a 14-month period. Visual acuity improved and
      retinal edema and exudation disappeared. The authors did not observe ocular or
      systemic side effects. In this view intravitreal injection of bevacizumab should
      be evaluated as a potentially effective therapy for peripapillary subretinal
      neovascularization, in particular for its extension in the papillomacular bundle.

PMID- 25389828
TI  - Soft-shell technique to maintain view of fundus after hemorrhage during
      vitrectomy in a patient with neovascular glaucoma.
AB  - BACKGROUND: Intraoperative hemorrhage into the anterior chamber can hamper the
      view of the fundus during vitreous surgery. We report a soft-shell technique that
      can be used to maintain a clear view of the entire fundus after intraoperative
      hemorrhage. METHODS: A 56-year-old man with rubeotic glaucoma and untreated
      diabetic retinopathy was scheduled to undergo vitrectomy with retinal
      photocoagulation. However, an intraoperative hemorrhage occurred from the iris
      and blocked a clear view of the fundus. RESULTS: The soft-shell technique was
      performed in which low viscoelastic material was injected into the anterior
      chamber followed by the injection of higher viscoelastic material. A clear
      surgical view of the entire fundus was obtained, and the clarity was maintained
      throughout peripheral vitrectomy and panretinal photocoagulation. The intraocular
      pressure was normalized after additional filtering surgery. CONCLUSIONS: We
      recommend the soft-shell technique as a method for obtaining and maintaining a
      clear view of the posterior pole if hemorrhage occurs in the anterior chamber
      during vitrectomy.

PMID- 25389829
TI  - Multifocal choroiditis in siblings.
AB  - PURPOSE: To describe multifocal choroiditis in two siblings. METHODS:
      Retrospective case reports. RESULTS: Two sisters presented 10 years apart with
      multifocal choroiditis. The first sister manifested late findings of multiple
      punched-out chorioretinal lesions and a quiescent central fibrovascular scar. The
      second sister presented in the acute phase with multiple creamy yellow lesions
      near the optic nerve and fovea and with a choroidal neovascular membrane. Both
      cases were unilateral. DISCUSSION: Multifocal choroiditis is an inflammatory
      disorder of the inner choroid and retinal pigment epithelium of unknown etiology.
      There is no gene associated with multifocal choroiditis, and to our knowledge, no
      cases of relatives with the disease have been reported. CONCLUSION: We describe
      multifocal choroiditis in two sisters, suggesting a possible genetic or
      environmental component to this disease. Further study is necessary to better
      elucidate the etiology of this disease.

PMID- 25389830
TI  - Indocyanine green angiographic findings of hypertensive choroidopathy.
AB  - PURPOSE: To evaluate fundus lesions in patients with malignant hypertension with
      indocyanine green angiography (ICGA). METHODS: Cases of hypertensive
      choroidopathy were followed prospectively with ICGA, fluorescein angiography
      (FA), and optical coherence tomography (OCT). RESULTS: In Case 1, a 34-year-old
      man had a 10-day history of blurred vision in both eyes. Visual acuity was 0.2 in
      the right eye and 0.01 in the left eye. Blood pressure (BP) was 270/178 mmHg, and
      laboratory tests disclosed severe renal dysfunction. In Case 2, a 31-year-old man
      had noticed blurred vision in both eyes. Visual acuity was 1.2 in the right eye
      and 1.0 in the left eye. BP was 272/180 mmHg. Marked optic edema, retinal
      hemorrhage, cotton-wool patches, and Elschnig spots were seen in both cases. FA
      showed poorly perfused choroid in the early phase and fluorescein dye leakage
      from the optic disk. OCT demonstrated serous retinal detachment in both cases.
      ICGA revealed Elschnig spots corresponding to the patchy choroidal filling
      defect. ICGA demonstrated a larger area of choroidal filling defect than FA. In
      Case 1, ICGA revealed dye leakage from large choroidal vessels. These OCT and
      ICGA findings reduced after early systemic treatment for malignant hypertension.
      CONCLUSION: Hypofluorescent spots in the choroid thought to be choriocapillaris
      occlusion and choroidal vessel damage recover as result of early treatment for
      malignant hypertension. ICGA is useful to reveal the disturbance of choroidal
      circulation in hypertensive choroidopathy.

PMID- 25389831
TI  - Electroretinography and microperimetry as noninvasive diagnostic tools for
      cilioretinal artery occlusion.
AB  - PURPOSE: To report a case of cilioretinal artery occlusion with normal
      fluorescein angiography findings that was evaluated by electroretinography (ERG)
      and microperimetry. METHODS: A 64-year-old-man presented with an oval paracentral
      scotoma in the temporal field of the left eye that became more evident after
      cataract surgery. Fundus photography, fluorescein angiography, ERG, multifocal
      ERG, and microperimetry were performed. RESULTS: Multifocal ERG showed decreased
      signal amplitudes in areas corresponding to areas with a visual defect as
      detected by microperimetry. Pattern ERG also showed a defect in the P50
      component. Findings of fundus photography, fluorescein angiography, and full
      field ERG were within normal limits. CONCLUSION: This case demonstrates the
      possibility of using ERG and microperimetry as noninvasive tools in the diagnosis
      of cilioretinal artery occlusion.

PMID- 25389832
TI  - Visual loss associated with accidental subretinal injection of triamcinolone
      acetonide.
AB  - PURPOSE: To describe a complication of and possible retinal toxicity associated
      with sub-Tenon space injection of triamcinolone acetonide (TA). METHODS: An
      interventional case report is presented. During attempted sub-Tenon space
      injection of TA suspension (40 mg/mL), ~0.3 mL was inadvertently injected into
      the temporal subretinal space. Potential sequelae of subretinal TA were assessed
      with fundus photography and visual field testing. RESULTS: Although subretinal TA
      resorbed quickly, a dense nasal visual field defect and retinal pigment
      epithelial changes corresponding to the area of initial subretinal TA deposition
      persisted for at least 18 months. CONCLUSION: Subretinal TA may exert retinal and
      retinal pigment epithelial toxicity.

PMID- 25389833
TI  - Partial regression of vitreoretinal lymphoma after fine needle aspiration biopsy.
AB  - PURPOSE: To report a case of regression of vitreoretinal lymphoma after fine
      needle aspiration biopsy. METHODS: Interventional case report. RESULTS: A 72-year
      old woman with a history of systemic non-Hodgkin lymphoma noted difficulty
      focusing with the right eye and was found to have multiple yellow sub-retinal
      pigment epithelium (sub-RPE) infliltrates. Fine-needle aspiration biopsy
      disclosed large atypical lymphocytes consistent with large-cell lymphoma. Four
      weeks after biopsy, the sub-RPE lesions resolved without additional treatment.
      Three months later, the tumors recurred. The patient received systemic
      chemotherapy, and her condition remained stable without brain involvement at the
      2-year follow-up. CONCLUSION: Fine-needle aspiration biopsy can induce temporary
      regression of vitreoretinal lymphoma. Patients with vitreoretinal lymphoma should
      have regular systemic follow-up examinations due to the risk of central nervous
      system recurrence.

PMID- 25389834
TI  - Testicular mixed germ-cell tumor metastatic to the choroid.
AB  - PURPOSE: To describe the fundus findings, ultrasonography, and fluorescein
      angiography of a testicular mixed germ-cell tumor metastatic to the choroid and
      to report prompt resolution of the choroidal lesion with systemic chemotherapy.
      METHODS: Observational case report. A 21-year-old man presented with a 10-cm
      testicular tumor. Ophthalmic examination revealed a large, dome-shaped choroidal
      lesion in the left eye, filling the entire superotemporal quadrant and extending
      into the macula. Ultrasonography showed a 10.3 mm in thickness hyperechoic mass.
      The patient was started on vinblastine, mesna, ifosfamide, and cisplatin.
      RESULTS: On ophthalmic examination 6 weeks after initiation of chemotherapy, the
      choroidal lesion had completely resolved, leaving only pigmentary changes. Final
      ophthalmology follow-up 8 months after presentation demonstrated no recurrence of
      choroidal metastases. CONCLUSION: Testicular germ-cell tumors have now been well
      described to metastasize to the choroid. These choroidal metastases can show a
      prompt, favorable response to chemotherapy.

PMID- 25389835
TI  - Photodynamic therapy for iris metastasis from a mediastinal carcinoid tumor.
AB  - PURPOSE: Intraocular metastasis from a carcinoid tumor is a rare event with
      anecdotal reports of iris involvement. We describe a case of iris metastasis from
      a carcinoid tumor treated with photodynamic therapy (PDT). METHODS: An isolated
      iris tumor was observed in a 36-year-old man. Anterior segment photography,
      fluorescein angiography, and fine-needle aspiration biopsy were performed. The
      tumor was treated with a bolus application of PDT. Regular follow-up (including
      clinical and angiographic evaluations) was performed over 2 years. RESULTS: The
      iris mass was cytologically consistent with metastasis from a mediastinal
      carcinoid tumor. The metastasis showed prominent vascularization. Bolus PDT was
      applied with complete and long-term regression of the iris tumor. At the 24-month
      follow-up, the patient was still alive, and no recurrence had been documented.
      CONCLUSIONS: PDT may be an effective therapeutic option in selected cases of iris
      metastasis.

PMID- 25389836
TI  - Acute idiopathic multifocal hemorrhagic retinal vasculitis with transient
      profound visual loss.
AB  - BACKGROUND: Acute idiopathic multifocal hemorrhagic retinal vasculitis is a rare
      entity. The diagnosis is based on typical fundus findings following exclusion of
      other more common conditions with similar features. The authors present a case
      that outlines their approach to diagnosis and management of a patient with
      simultaneous bilateral presentation. METHOD: Retrospective case report. RESULTS:
      This diagnosis often carries a poor prognosis. However, the reported patient did
      well, with an improvement in vision from light perception in the right eye and
      hand motions in the left eye at presentation to 20/60 in the right eye and 20/25
      in the left eye at 24-month follow-up. Management included intravitreal
      ganciclovir, oral corticosteroids, panretinal photocoagulation in both eyes, and
      vitrectomy in one eye. CONCLUSION: Patients with acute idiopathic multifocal
      hemorrhagic choroiditis can exhibit delayed and substantial visual improvement
      despite initial profound visual loss. The authors discuss this case and review
      the current understanding of the diagnosis and management of this disease.

PMID- 25389837
TI  - Recurrence of acute lymphocytic leukemia diagnosed by subretinal biopsy.
AB  - PURPOSE: To report a case of leukemia relapse in the subretinal space that was
      diagnosed by transvitreal subretinal biopsy. METHODS: Case report and literature
      review. RESULTS: A 5-year-old girl with prior history of acute lymphocytic
      leukemia who was in clinical remission was examined for a unilateral subretinal
      mass. Her systemic evaluation was negative for recurrence of the acute
      lymphocytic leukemia. Pars plana vitrectomy with a subretinal biopsy showed
      leukemic cells confirmed by flow cytometric immunophenotyping. The patient
      subsequently underwent bone marrow transplantation with regression of the
      subretinal mass. CONCLUSION: Leukemia relapse may occur in the subretinal space.
      A relapse may be successfully diagnosed with a subretinal biopsy through a pars
      plana vitrectomy.

PMID- 25389838
TI  - Epibulbar foreign body granuloma masquerading as extrascleral extension following
      brachytherapy for choroidal melanoma.
AB  - PURPOSE: To describe a patient with epibulbar foreign body granuloma following
      brachytherapy for choroidal melanoma and to illustrate the echographic features
      that aided in the differential diagnosis. METHODS: Observational case report.
      Patient had multiple clinical exams over time to evaluate a treated choroidal
      melanoma. PATIENTS: A 61-year-old man presented for echographic follow-up
      examination following treatment for choroidal melanoma. An epibulbar lesion was
      noted adjacent to the site of the previously treated choroidal melanoma.
      Incisional biopsy and histologic evaluation were required. RESULTS:
      Ultrasonography revealed regression of the intraocular tumor; however, an oval
      epibulbar mass with irregular internal structure, irregular reflectivity, and no
      vascularity was noted. The echographic features were not typical of extrascleral
      extension of choroidal melanoma. Histopathologic evaluation showed fibrous
      connective tissue with an intense infiltrate of histiocytes with occasional giant
      cells and rare birefringent foreign body materials. CONCLUSION: Foreign body
      granuloma should be considered in the echographic differential diagnosis of an
      atypical extrascleral lesion following uveal melanoma brachytherapy.

PMID- 25389839
TI  - Optic nerve invasion from an amelanotic peripapillary choroidal melanoma.
AB  - PURPOSE: To report an unusual case of an amelanotic optic nerve head melanoma.
      PATIENTS/METHODS/RESULTS: This is a retrospective case report of an 81-year-old
      woman with a slowly enlarging amelanotic optic nerve head lesion. Histopathologic
      evaluation of the lesion after enucleation revealed a peripapillary choroidal
      melanoma. The lesion was highly atypical in that the patient's visual acuity was
      excellent despite the lesion's growth and the intraocular pressure did not differ
      from the fellow eye. The patient did have a history of primary open angle
      glaucoma, which may have rendered the optic nerve more susceptible to tumor
      invasion. CONCLUSION: Optic nerve invasion by choroidal melanoma is a rare event,
      which is typically associated with poor visual acuity, elevated intraocular
      pressure, and large necrotic lesions; however, invasive melanoma with optic nerve
      invasion may occur in the absence of these classic findings.

PMID- 25389840
TI  - Intravitreal triamcinolone acetonide in the treatment of macular retinal
      detachment associated with morning glory anomaly.
AB  - PURPOSE: To report the successful treatment of a case of recurrent macular
      retinal detachment associated with morning glory anomaly using intravitreal
      triamcinolone acetonide. METHODS: A 53-year-old man with a history of bilateral
      morning glory anomaly and recurrent macular detachment of the left eye refractory
      to multiple surgical interventions, including 3 vitrectomies with endolaser
      photocoagulation, gas tamponade, and fibrin glue, underwent an intravitreal
      injection of 4 mg triamcinolone acetonide. RESULTS: A single treatment with
      intravitreal triamcinolone acetonide resulted in resolution of a macular retinal
      detachment and intraretinal fluid within 2 weeks. CONCLUSION: Treatment with
      intravitreal triamcinolone acetonide may be beneficial in cases of macular
      retinal detachment associated with morning glory anomaly.

PMID- 25389841
TI  - Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate
      (depo-medrol) injection during pars plana vitrectomy.
AB  - PURPOSE: Methylprednisolone acetate (Depo-Medrol, Pfizer, New York) is a depot
      corticosteroid that is commonly injected periorbitally to treat various
      ophthalmologic conditions. Accidental intravitreal injections secondary to globe
      perforations have resulted in rapid retinal toxicity. To their knowledge, the
      authors report the first case of inadvertent intravitreal methylprednisolone
      acetate injection during pars plana vitrectomy. METHOD: Report of a case of
      inadvertent intravitreal injection of methylprednisolone acetate, mistaken as
      triamcinolone acetonide, during repeated retinal detachment repair. RESULTS: The
      affected eye had loss of vision, afferent pupillary defect, optic nerve atrophy,
      retinal necrosis, retinal vascular damage, and recurrent retinal detachment.
      DISCUSSION: Methylprednisolone acetate administered during vitrectomy causes
      severe retinal toxicity and complicates retinal detachment repair. It is
      important to use measures to avoid erroneous intravitreal injections during
      vitrectomy.

PMID- 25389842
TI  - Ocular rupture after accidental intraocular injection of bupivacaine.
AB  - PURPOSE: To report on the toxicity of bupivacaine that was accidentally injected
      into the eye. METHODS: Observational case report. Clinical and
      electroretinographic examinations of a 78-year-old woman who had an ocular
      rupture after an accidental intraocular injection of 0.25% bupivacaine. RESULTS:
      The a- and b-waves of the electroretinographics were normal after the repair of
      the eye by vitrectomy. The corneal opacification and edema present after the
      rupture did not recover. CONCLUSION: The exposure of the retina to 0.25%
      bupivacaine may not alter the function of the human retina.

PMID- 25389843
TI  - Removal of large subretinal foreign bodies with bimanual vitrectomy and use of a
      suture loop.
AB  - PURPOSE: To describe removal of large subretinal foreign bodies with bimanual
      pars plana vitrectomy and use of a suture loop. METHODS: In a retrospective
      interventional case series, 2 eyes of 2 patients referred 1 month after primary
      wound suturation, both with posttraumatic retinal detachment and 1 with
      endophthalmitis, underwent pars plana vitrectomy. Intraocular foreign bodies
      (IOFBs) were grasped using a 6-0 polypropylene suture loop. The loop was placed
      around the IOFBs using an intraocular forceps, and the foreign bodies were
      extracted from the eyes. RESULTS: A suture loop was placed around the IOFB
      bimanually, and removal was performed as described. Two large subretinal IOFBs,
      one metallic and one nonmetallic, were removed successfully without slippage, the
      first through a limbal incision and the second through an enlarged sclerotomy.
      The patients were observed for 3 months. One eye had retinal attachment, but the
      other eye had redetachment that was considered inoperable. CONCLUSION: Large
      metallic and nonmetallic subretinal IOFBs of different shapes and sizes can be
      removed with a suture loop, but in complicated cases, bimanual placement of the
      loop may provide better control for IOFB removal and the ability to surround the
      IOFB at its desired axis, thereby decreasing the size of the incision for
      extraction.

PMID- 25389844
TI  - Femtosecond laser can cause choroidal rupture.
AB  - PURPOSE: Many studies have found that it is very difficult to create choroidal
      lesions using a femtosecond laser. However, a patient with a premacular
      hemorrhage in the left eye and a choroidal rupture in the right eye from exposure
      to reflection of a femtosecond laser from a metal is described. METHODS: The
      patient was treated with intravitreal expansile gas to displace the premacular
      blood in the left eye on posttrauma day 2. PATIENTS: A 51-year-old man presented
      with blind spots in both eyes after being exposed to reflection of a femtosecond
      laser from a metal. RESULTS: At the 10-week follow-up, the patient's vision
      improved to 20/40 (20/30 with a pinhole in the left eye). DISCUSSION: This case
      suggests that choroidal rupture may occur with use of a femtosecond laser system.

PMID- 25389845
TI  - Simultaneous presentation of retinoblastoma and morning glory disk anomaly.
AB  - PURPOSE: To describe a patient with retinoblastoma and morning glory disk anomaly
      (MGDA). METHOD: Observational case report. RESULTS: A 7-month-old girl with
      bilateral retinoblastoma was found to have concurrent MGDA in the less involved
      eye. The more severely affected eye was enucleated due to progressive disease not
      amenable to aggressive systemic and local treatment; histologic analysis was
      performed. CONCLUSION: Prompt ocular examination of a pediatric patient should be
      performed in the presence of concerning findings such as leukokoria or
      strabismus. In addition, more than one ocular abnormality may coexist, such as
      retinoblastoma and MGDA, necessitating complete examination.

PMID- 25389846
TI  - Transpupillary thermotherapy for vasoproliferative retinal tumor.
AB  - PURPOSE: To report the clinical course of a patient with vasoproliferative
      retinal tumor (VPRT) who was treated with transpupillary thermotherapy (TTT).
      METHODS: A 50-year-old asymptomatic woman who had undergone fundus examination as
      a part of a preventive medical examination and been diagnosed with a retinal
      tumor in the left eye was referred to our hospital. Photocoagulation failed to
      inhibit progression of the massive serous detachment that accompanied the tumor,
      and TTT was performed with an 810-nm diode laser with a 4.0-mm spot size at 500
      mW to 750 mW for 60 seconds with a 1-month interval between 2 treatments. Four
      and two partially overlapping laser spots were applied to cover the entire tumor
      in the first and second treatment sessions, respectively. As a result, the laser
      was applied to the tumor until the lesion become white. RESULTS: The serous
      retinal detachment and macular edema had almost completely resolved after two
      sessions of TTT. Thirteen months after TTT, there was no recurrence of the tumor.
      CONCLUSION: There were no complications associated with TTT for VPRT. Further
      follow-up of this case as well as accumulative data from other case reports is
      still needed, but TTT may be effective for treating VPRT with severe retinal
      detachment.

PMID- 25389847
TI  - Bietti crystalline dystrophy with bilateral macular holes.
AB  - OBJECTIVE: Bietti crystalline dystrophy is a rare form of tapetoretinal
      degeneration associated with retinal crystalline deposits. However, Bietti
      crystalline dystrophy is extremely unusually associated with macular hole
      formation. A 32-year-old man with Bietti crystalline dystrophy and bilateral
      macular holes is described. DESIGN: Case report and literature review. RESULTS:
      Clinical and angiographic features, optical coherence tomography results,
      electroretinographic findings, and visual evoked potentials are reported.
      CONCLUSION: Bietti crystalline dystrophy can occur with bilateral macular holes,
      but the cause is unclear.

PMID- 25389848
TI  - Peripheral polypoidal choroidal neovascularization, subretinal hemorrhage, and
      cataract surgery.
AB  - BACKGROUND: Spontaneous choroidal hemorrhages during uneventful cataract surgery
      are rare, potentially disastrous, and poorly understood. We describe three
      patients with spontaneous limited peripheral choroidal hemorrhages and associated
      polypoidal choroidal neovascularization. METHOD: Case series. RESULTS: Peripheral
      polypoidal choroidal vasculopathy was identified as an underlying potential
      causative factor in these patients with spontaneous limited choroidal hemorrhage
      during uneventful cataract surgery. CONCLUSION: Polypoidal choroidal
      vasculopathy, known to occur in the peripheral fundus, may be a mechanism for
      spontaneous limited or explosive peripheral fundus subretinal hemorrhages at the
      time of anterior segment surgery. These hemorrhages may not require
      interventional treatment in that regression of the associated neovascularization
      and resolution of the serosanguineous manifestations may occur without
      significant vision loss.

PMID- 25389849
TI  - Silicone oil-induced corneal perforation following complex retinal detachment.
AB  - PURPOSE: To report a case of silicone oil-induced corneal perforation following
      complex retinal detachment surgery. METHODS: Case report. RESULTS: Two months
      following a second retinal detachment repair, the patient presented to eye
      casualty with a corneal perforation secondary to silicone oil keratopathy.
      CONCLUSION: The pathophysiology of silicone oil-related perforation is not
      clearly understood. Poor corneal nutrition due to the presence of oil may be an
      important contributory factor. Close monitoring of patients for early signs of
      silicone oil keratopathy could preempt perforation.

PMID- 25389850
TI  - A case of purtscher-like retinopathy following a motor vehicle accident.
AB  - PURPOSE: To describe a case of Purtscher-like retinopathy following seat belt
      compression of the chest in a motor vehicle accident. METHODS: Case report.
      RESULTS: A 53-year-old woman developed Purtscher-like retinopathy following
      compression of the chest by her seat belt in a motor vehicle accident.
      Observation was recommended, and on follow-up examination at 8 weeks her vision,
      fluorescein angiography, and optical coherence tomography had returned to
      baseline. CONCLUSION: Seat belts may produce chest compression to induce a
      Purtscher-like retinopathy in varying degrees associated with the severity of the
      accident and subsequent compressive forces of the seat belt.

PMID- 25389851
TI  - Aplastic anemia secondary to 6-mercaptopurine initially presenting with a
      hemorrhagic retinopathy.
AB  - PURPOSE: To describe a case of hemorrhagic retinopathy secondary to aplastic
      anemia caused by 6-mercaptopurine. METHODS: A case report of a patient who
      presented as an outpatient to the Ophthalmology service of the New York
      Presbyterian Hospital. CONCLUSION: To the authors' knowledge, this is the first
      reported case of hemorrhagic retinopathy secondary to aplastic anemia caused by 6
      mercaptopurine.

PMID- 25389852
TI  - Central serous chorioretinopathy associated with the use of ephedra.
AB  - PURPOSE: To report three cases of central serous chorioretinopathy (CSC) likely
      related to the use of body-building products containing ephedra. METHODS:
      Observational case series of three patients who presented with signs and symptoms
      of CSC. All cases had ocular coherence tomography and fluorescein angiograms to
      confirm the diagnosis. All admitted to current or previous use of ephedra
      containing products for body building. No patient had a history of current or
      prior use of steroids. RESULTS: The first patient presented in 2005 with a 7
      month history of bilateral CSC. On careful history, the patient admitted to the
      use of ephedra during body-building exercises. After discontinuation of the
      ephedra, his CSC resolved. The second and third patients presented in 2007. Both
      had pigmented epithelial detachments in both eyes secondary to CSC and atrophic
      changes suggestive of old, resolved CSC. The second patient had admitted to the
      use of ephedra 3 years previously and Patient 3 was currently using an ephedra
      containing body-building product. After Patient 3 discontinued the ephedra, his
      CSC too resolved. CONCLUSION: We report three cases of CSC related to the use of
      ephedra-containing products. All three cases were chronic, atypical, and
      bilateral in nature with two of three cases resolving after the discontinuation
      of the ephedra. This may be related to the sympathomimetic properties of ephedra
      as reported by Michael et al for pseudoephedrine. Given these findings, we
      suggest that questioning about ephedra products become standard when taking
      histories in suspected CSC cases.

PMID- 25389853
TI  - Ocular ischemia in high myopia treated with intravenous prostaglandin e1.
AB  - BACKGROUND: High myopia is associated with a decreased ocular blood flow. In some
      cases this ocular ischemia may be the cause of severe visual loss. METHODS: Three
      patients with high myopia and progressive loss of visual acuity had a diagnosis
      of ocular ischemia by color Doppler. Intravenous prostaglandin E1, a powerful
      vasodilator of the microcirculation, was used to treat the ocular ischemia in all
      3 patients. RESULTS: The visual acuity improved in all three cases with one
      patient improving from 20/100 to 20/30. The mean deficit of the visual fields in
      this patient improved from -19.08 to -9.52 after treatment. The treatment was
      repeated every 6 weeks to 8 weeks. CONCLUSION: Patients with high myopia and
      progressive visual acuity loss should be evaluated for ocular ischemia.
      Intravenous prostaglandin E1 should be considered in those cases of ocular
      ischemia with visual loss. Unfortunately the effect does not last for more than 6
      weeks to 8 weeks and needs to be repeated at this interval for extended periods.

PMID- 25389854
TI  - Cystoid macular edema secondary to Paclitaxel (abraxane).
AB  - PURPOSE: To report a case of cystoid macular edema secondary to systemic
      paclitaxel. METHODS: A 58-year-old man with Stage 4 metastatic cutaneous melanoma
      presented with decreased vision and macular edema while having minimal
      fluorescein leakage 7 months into a course of paclitaxel chemotherapy. The edema
      continued to worsen, and vision declined until paclitaxel therapy was
      discontinued. Six weeks after cessation of paclitaxel, the edema had completely
      resolved and vision returned to normal. CONCLUSION: Paclitaxel use can result in
      reversible vision loss associated with angiographically silent macular edema.

PMID- 25389855
TI  - Bilateral panuveitis after influenza vaccination.
AB  - PURPOSE: To report a case of bilateral panuveitis after systemic administration
      of the influenza vaccination. METHODS: Case report. RESULTS: Bilateral panuveitis
      after systemic administration of the influenza vaccination, which resolved after
      local and systemic treatment. DISCUSSION: Although uveitis secondary to
      vaccinations has been reported previously, this is only the second reported case
      of bilateral panuveitis after administration of the influenza vaccine.

PMID- 25389856
TI  - Photodynamic therapy for choroidal neovascularization in stargardt disease and
      retinitis pigmentosa.
AB  - PURPOSE: To report the successful use of photodynamic therapy (PDT) in three
      patients with choroidal neovascularization (CNV) secondary to retinal
      dystrophies. METHODS: Three patients who presented for blurring of vision were
      found to have CNV on fluorescein angiography. Two patients had retinitis
      pigmentosa and one patient had Stargardt disease. They underwent standard regime
      of PDT. RESULTS: Resolution of hemorrhage with improvement of visual acuity was
      seen in all three patients after one round of PDT. One patient required a second
      round of PDT because of the recurrence of CNV. Two patients were subsequently
      followed up for at least 2 years and 1 patient who defaulted after the 3 month
      follow-up showed no recurrence. CONCLUSION: Stargardt disease and retinitis
      pigmentosa are common retinal dystrophies. We report our successful treatment of
      CNV with PDT in two patients with retinitis pigmentosa and one patient with
      Stargardt disease. Despite the increasing use of antivascular endothelial growth
      factors drugs, standard treatments can still be applied to certain forms of CNV.

PMID- 25389857
TI  - Surgical management of massive submacular hemorrhage associated with age-related
      macular degeneration.
AB  - PURPOSE: To investigate the safety and efficacy of surgical drainage of massive
      and elevated submacular hemorrhage associated with age-related macular
      degeneration through circumferential peripheral 180 degrees  temporal retinotomy.
      METHODS: Prospective interventional case series of first eyes of six consecutive
      patients with large elevated submacular hemorrhage. The surgical approach
      consisted of combined cataract surgery, three-port pars plana vitrectomy,
      induction of retinal detachment, and circumferential peripheral temporal 180
      degrees  retinotomy. The temporal retina was reflected and the solid blood clot
      was removed with a vitreous cutter along with the choroidal neovascular complex.
      Silicone oil was used as an internal temponade in all patients. Complete clinical
      examination was performed in all cases preoperatively and postoperatively at 1
      and 3 months. After removal of silicone oil, the patients were observed for 12
      months. RESULTS: Submacular hemorrhage was completely removed in all cases the
      next day after the surgery. All patients experienced improvement of central
      scotoma. Twelve months after silicone oil removal, visual acuity was defined as
      improvement in 5 eyes (83%) and stable in 1 eye (17%). No recurrence or
      complications were observed during the period of follow-up. CONCLUSION: Our
      surgical approach could be efficacious to remove a large elevated submacular
      hemorrhage that is not feasible for any other treatment. It may help to improve
      the central scotoma and results in limited visual improvement in selected
      patients.

PMID- 25389858
TI  - Solitary idiopathic choroiditis with choroidal neovascularization.
AB  - PURPOSE: To report a case of solitary idiopathic choroiditis associated with
      choroidal neovascularization. METHOD: Case report of a 36-year-old healthy man
      who was referred for floaters in the left eye of 3 weeks' duration. RESULTS:
      Fundus examination of the left eye revealed a yellow-white subretinal lesion
      superior to the fovea. It was associated with a small subretinal hemorrhage and a
      macular detachment, which extended into the fovea. No vitreous cells were
      detected. The right eye was normal. The visual acuity was 20/20 in the right eye
      and 20/50 in the left eye. Laboratory evaluation for inflammatory or infectious
      diseases was nonrevealing. Fluorescein angiography showed Type 2 or so-called
      classic choroidal neovascularization associated with retinochoroidal anastomoses.
      After two laser treatments with poor outcomes, the lesion was effectively treated
      with oral steroids. A reactivation occurred 1.5 years later, and it was also
      successfully treated with oral steroids. CONCLUSION: Solitary idiopathic
      choroiditis can rarely be associated with choroidal neovascularization. Oral
      steroid treatment seems to be the preferred form of therapy rather than some form
      of interventional modality.

PMID- 25389859
TI  - Surgically induced necrotizing scleritis and optic neuropathy after pars plana
      vitrectomy as presenting signs of churg-strauss syndrome.
AB  - PURPOSE: To report a case of surgically induced necrotizing scleritis and optic
      neuropathy after pars plana vitrectomy as presenting signs of Churg-Strauss
      syndrome. METHOD: Case report. RESULTS: A 59-year-old Asian man underwent a 20
      gauge pars plana vitrectomy to remove a posteriorly dislocated intraocular lens.
      During follow-up, he developed unilateral necrotizing scleritis and optic
      neuropathy. Systemic evaluation and laboratory investigations revealed findings
      consistent with Churg-Strauss syndrome. Systemic corticosteroids therapy produced
      dramatic improvement in visual symptoms. CONCLUSION: Churg-Strauss syndrome
      should be considered in any patient who develops surgically induced necrotizing
      scleritis and/or optic neuropathy after pars plana vitrectomy. Prompt and
      aggressive treatment with systemic corticosteroids can result in marked
      improvement.

PMID- 25389860
TI  - Retinal imaging with high-resolution high-speed optical coherence tomography in
      patients with nystagmus.
AB  - PURPOSE: To compare the quality of retinal images in patients with nystagmus made
      by the Spectral Domain High-Resolution High-Speed Optical Coherence Tomography
      Copernicus (SD-OCT) and by the Time Domain Stratus Optical Coherence Tomography
      (Stratus-OCT). METHODS: Three patients with a congenital horizontal nystagmus and
      various retinal features were tested with both the SD-OCT (Optopol, Rockmed,
      Poland) and the standard Stratus-OCT (Carl Zeiss Meditec, Dublin, CA). RESULTS:
      Stratus-OCT exhibited "saw tooth" or waved images in all three patients with
      nystagmus and failed to discriminate the retinal layers. In contrast, the SD-OCT
      imaging gave clear representation of the retina with discrimination of
      intraretinal layers in all three patients. CONCLUSION: The high speed and
      resolution of SD-OCT resulted in discrimination of intraretinal layers in
      patients with nystagmus and indicates the potential of SD-OCT in diagnosing
      retinal disorders in patients with nystagmus.

PMID- 25389861
TI  - Indocyanine green angiographic features in a case of alkali retinopathy.
AB  - PURPOSE: To report the fluorescein and indocyanine green angiographic features of
      a patient who developed posterior segment complications after an ocular alkali
      burn. METHODS: Clinical examination, fluorescein angiography, and indocyanine
      green angiography were performed on a patient with an ocular alkali injury.
      RESULTS: Clinical examination revealed an area of conjunctival and scleral
      necrosis in the injured eye. There was an area of retinal necrosis, which
      corresponded to the area of external necrosis. Fluorescein angiography
      demonstrated late leakage and obliteration of the retinal vessels in the area of
      necrosis. There was nonperfusion of the choroid with a surrounding rim of late
      indocyanine green leakage. CONCLUSION: Alkaline substances can penetrate sclera.
      Ocular alkali burns can result in choroidal ischemia and retinal necrosis. It is
      important to suspect posterior segment complications in all ocular alkali
      injuries. This case emphasizes the necessity of prompt irrigation of the
      conjunctival cul de sac and the removal of any solid chemical remnants after
      ocular alkali injuries.

PMID- 25389862
TI  - Methicillin-resistant Staphylococcus aureus infectious scleritis after vitrectomy
      for endophthalmitis.
AB  - PURPOSE: To report a case of methicillin-resistant Staphylococcus aureus
      infectious scleritis after vitrectomy for endophthalmitis. METHODS: Retrospective
      chart review of one patient referred to a tertiary academic center for management
      of methicillin-resistant S. aureus infectious scleritis. Antecedent history,
      clinical course, response to treatment, and final visual acuity were documented.
      RESULTS: Methicillin-resistant S. aureus infectious scleritis required
      combination systemic, periocular, intraocular, and topical antibiotics for
      complete resolution. Visual recovery was limited. CONCLUSION: Methicillin
      resistant S. aureus infectious scleritis can complicate vitrectomy for
      endophthalmitis and requires long-term and multiple-route administration of
      antibiotics for resolution. Greater awareness of this serious complication along
      with preventive measures may reduce future occurrences.

PMID- 25389863
TI  - Intravitreal ranibizumab for choroidal neovascularization secondary to choroidal
      nevus.
AB  - PURPOSE: To describe a patient treated with ranibizumab for juxtafoveal choroidal
      neovascularization secondary to choroidal nevus. METHODS: A 71-year-old man
      presented with juxtafoveal choroidal neovascularization secondary to choroidal
      nevus. Choroidal neovascularization was initially treated with a single
      intravitreal injection of ranibizumab. RESULTS: The treatment was successful and
      best-corrected visual acuity improved from 20/50 to 20/25 and remained stable
      during 7 months. A recurrence was observed 9 months after initial treatment.
      CONCLUSION: Ranibizumab seems to be an effective treatment for choroidal
      neovascularization secondary to choroidal nevus. However, late recurrence may
      occur.

PMID- 25389864
TI  - Retinal neovascularization associated with a retinal arterial macroaneurysm.
AB  - PURPOSE: This case report describes an uncommon presence of a retinal arterial
      macroaneurysm complicated by retinal neovascularization. METHODS: This is a case
      history of a 49-year-old woman presenting with preretinal, intraretinal, and
      subretinal hemorrhage with an adjacent retinal arterial macroaneurysm complicated
      by the development of retinal neovascularization. RESULTS: The
      neovascularization, intraretinal lipid, and retinal and preretinal hemorrhage
      resolved after laser photocoagulation, topical steroids, and nonsteroidal
      antiinflammatory agent treatment. CONCLUSION: The rapid development of a large
      frond of neovascularization is atypical for retinal arterial macular aneurysms
      and has not been previously reported.

PMID- 25389865
TI  - Outer retinal folds in highly myopic macular hole and retinal detachment.
AB  - PURPOSE: To report the intraretinal microstructure in macular hole and retinal
      detachment in a highly myopic eye using spectral-domain optical coherence
      tomography. METHODS: Two eyes of two patients with macular holes and retinal
      detachment were examined with spectral-domain optical coherence tomography.
      Fundus photographs and time-domain optical coherence tomography images also were
      obtained. RESULTS: Spectral-domain optical coherence tomography disclosed outer
      retinal fold formation toward the subretinal space at the level of the
      photoreceptor inner and outer segment layer, the cystoid spaces expanding outside
      of the macular hole and epiretinal membrane in all eyes. CONCLUSION: The outer
      retinal fold may indicate the tension of the inner retina and the redundancy of
      the outer retina, which may be responsible for the occurrence of macular holes
      and retinal detachment in these eyes.

PMID- 25389866
TI  - Three-dimensional optical coherence tomography for rhegmatogenous retinal
      detachment in posterior staphyloma.
AB  - PURPOSE: The detection of microretinal breaks in posterior staphyloma is
      frequently challenging. We evaluated the ability of three-dimensional optical
      coherence tomography to detect retinal breaks in posterior staphyloma. PATIENTS:
      We prospectively examined two highly myopic eyes of two patients with
      rhegmatogenous retinal detachment in posterior staphyloma. RESULTS: Retinal
      breaks could not be detected in any of the two eyes by conventional fundus
      examination; however, these breaks were easily detected on the series of B-scan
      optical coherence tomography images. The location of retinal breaks was
      registered in the color fundus photographs, and it corresponded well with the
      findings during vitrectomy. CONCLUSION: Three-dimensional optical coherence
      tomography seems to be an effective tool for detecting microretinal breaks and is
      useful in vitrectomy for rhegmatogenous retinal detachment in the area with
      posterior staphyloma.

PMID- 25389867
TI  - De novo emergence of a circumscribed choroidal hemangioma in a premature infant.
AB  - PURPOSE: To present a case of a premature infant who was witnessed to have de
      novo development of a circumscribed choroidal hemangioma over the course of
      routine retinopathy of prematurity screening. METHODS: Retrospective case report.
      RESULTS: A former 29-week, 1446-g premature infant boy was examined multiple
      times by both a pediatric retinal specialist and pediatric ophthalmologist before
      a posterior pole circumscribed choroidal hemangioma was noted, initially at
      postmenstrual age 39 weeks. The tumor remained fairly stable until the most
      recent follow-up examination at 2 years of age when it was noted to be much less
      prominent. CONCLUSION: Circumscribed choroidal hemangiomas previously have been
      thought to be congenital in nature. We present the earliest described case as
      well as the first de novo emergence of such a tumor.

PMID- 25389868
TI  - Contact lens intraocular foreign body presenting 1 year after traumatic open
      globe repair.
AB  - PURPOSE: To describe an intraocular contact lens presenting as a foreign body 1
      year after repair of a traumatic open globe. METHOD: A case report. RESULTS: The
      patient underwent open globe repair for a scleral laceration. The patient's
      vision returned to 20/20 and had no ocular complaints until 1 year later when he
      had a large floater. Examination revealed an intraocular contact lens in the
      anterior vitreous that was successfully removed by pars plana vitrectomy. The
      patient's vision returned to 20/20 with resolution of his floater. CONCLUSION:
      Ophthalmologists should be aware that a contact lens can gain access to the
      posterior segment in the setting of trauma. These intraocular foreign bodies can
      remain asymptomatic and undiagnosed for an extensive period of time until they
      gradually migrate into the visual axis.

PMID- 25389869
TI  - Sclerochoroidal calcification in a patient with chronic hypercalcemia from
      undiagnosed parathyroid adenoma.
AB  - PURPOSE: To describe a case of sclerochoroidal calcification in a patient with
      hypercalcemia from undiagnosed parathyroid adenoma. METHODS: A 66-year-old white
      woman was found to have asymptomatic bilateral yellow choroidal tumors
      characteristic of sclerochoroidal calcification. The calcified tumors were
      echogenic on ultrasonography. RESULTS: Systemic evaluation disclosed
      hypercalcemia, and there was no abnormality of the parathyroid glands with
      hormone levels or nuclear medicine scans. After 4 years, the hypercalcemia
      persisted, prompting surgical exploration of the parathyroid glands that revealed
      an adenoma. After resection of the glands, the serum calcium reverted to normal.
      DISCUSSION: Sclerochoroidal calcification can be associated with systemic
      hypercalcemia. A search for the cause is warranted, and in this case, a
      subclinical adenoma was the source of the hypercalcemia.

PMID- 25389870
TI  - Indocyanine green angiography features of central areolar choroidal dystrophy.
AB  - PURPOSE: Central areolar choroidal dystrophy is an inherited autosomal dominant
      macular disease characterized by a central atrophy of the retinal pigment
      epithelium and choriocapillaris. Our purpose was to describe fluorescein
      angiography and confocal indocyanine green angiography features of central
      areolar choroidal dystrophy. METHODS: We performed a complete ophthalmologic
      examination including best corrected visual acuity, fundus examination, color
      fundus photographs, red free frames, fluorescein angiography, infrared, confocal
      indocyanine green, and electroretinography in a cohort of patients with a family
      history of central areolar choroidal dystrophy. RESULTS: Eleven patients (22
      eyes) affected were prospectively included. Indocyanine green differentiated two
      distinct phenotypes. In 9/11 patients, atrophy area was hyperfluorescent or
      normofluorescent. In the two other patients, the lesion was hypofluorescent from
      early to late phases and pinpoints were observed on the late phases. CONCLUSION:
      In our small series, indocyanine green angiography distinguished two phenotypes
      of central areolar choroidal dystrophy, correlated with fluorescein angiography
      features.

PMID- 25389871
TI  - Chronic curvularia lunata endophthalmitis following cataract extraction.
AB  - PURPOSE: To describe a case of chronic endophthalmitis after cataract extraction
      caused by an unusual pathogen. METHODS: Chart review. RESULTS: A 79-year-old male
      presented with chronic endophthalmitis from Cuvularia lunata and received
      vitrectomy with serial injections of intravitreal voriconazole. CONCLUSION:
      Curvularia endophthalmitis presents late and is difficult to eradicate but
      responds to intravitreal voriconazole.

PMID- 25389872
TI  - Florid polyclonal lymphoid follicular hyperplasia presenting as leopard spot
      retinopathy.
AB  - PURPOSE: To describe a case of leopard spot retinopathy associated with a
      systemic polyclonal lymphoproliferative disorder. Other described causes of this
      clinical finding are reviewed. METHODS: Case report. A previously healthy 50-year
      old white male presented with decreased vision. Examination showed leopard spot
      retinopathy. He underwent ophthalmic and body imaging, laboratory workup, and
      biopsy of a lymph node and lacrimal gland. RESULTS: The workup revealed a
      systemic polyclonal lymphoproliferative disorder which involved the orbit, lymph
      nodes, pancreas, kidney, and choroid. CONCLUSION: Leopard spot retinopathy is a
      clinical description associated with multiple etiologies. Choroidal infiltration
      related to a systemic polyclonal lymphoproliferative disorder is one cause.

PMID- 25389873
TI  - A case for the case report and case series in evidence-based management of
      retinal disease.

PMID- 25389874
TI  - Outer retinal dysfunction in a patient with the 15257 mitochondrial DNA mutation.
AB  - PURPOSE: The purpose of this study was to report a case of outer retinal
      dysfunction in a patient harboring the 15257 mitochondrial DNA mutation
      associated with Leber hereditary optic neuropathy. METHODS: A 43-year-old woman
      presented with a 6-month history of painless progressive visual loss in the right
      eye. She was found to have a right afferent pupillary defect, mild optic disk
      pallor, normal retinal vasculature, and mild retinal pigment epithelial changes
      in the macula of both eyes. She underwent optical coherence tomography of the
      macula of both eyes, multifocal electroretinography, and genetic testing for
      Leber hereditary optic neuropathy. RESULTS: Optical coherence tomography showed
      thinning of the outer retina, and multifocal electroretinography showed
      isoelectric waveforms centrally with markedly depressed amplitudes beyond the
      central five rings in both eyes. Genetic testing showed that the patient harbored
      the 15257 mitochondrial DNA mutation associated with Leber hereditary optic
      neuropathy. CONCLUSION: The 15257 mitochondrial DNA mutation may be associated
      with outer retinal dysfunction in addition to Leber hereditary optic neuropathy.

PMID- 25389875
TI  - Exudative retinal detachment and angle closure glaucoma as the presenting signs
      of primary pulmonary hypertension.
AB  - BACKGROUND: Primary pulmonary arterial hypertension is a rare systemic condition
      that may present with distinct ocular findings. PURPOSE: To report a patient
      whose ophthalmic manifestations led to a diagnosis of pulmonary arterial
      hypertension. RESULTS: A 58-year-old woman presented with bilateral serous
      detachments, angle closure, dilated episcleral blood vessels, subretinal
      drusenoid-like deposits, and intraretinal hemorrhages. She was diagnosed with
      pulmonary arterial hypertension. Her ocular findings resolved once her underlying
      systemic disorder had been treated. CONCLUSION: To our knowledge, this is the
      first reported case in which an ophthalmic evaluation led to the diagnosis of
      pulmonary arterial hypertension.

PMID- 25389876
TI  - Cystoid changes within astrocytic hamartomas of the retina in tuberous sclerosis.
AB  - PURPOSE: The purpose of this study was to report two unusual cases of cavitations
      within astrocytic hamartoma, a feature that causes the tumor to appear cystic. To
      our knowledge, this is the first report on cavitary astrocytic hamartoma.
      METHODS: In this observational case report, we identify two cases of cavitary
      astrocytic hamartoma imaged recently with spectral domain-optical coherence
      tomography. RESULTS: In both of our patients, the cavitary portion was visible
      clinically as an empty cavity surrounded by translucent tissue. Optical coherence
      tomography examination of both cases confirmed the presence of a cavity
      surrounded by tumor tissue. CONCLUSION: In these two patients, optical coherence
      tomography showed a new feature of cavitation within retinal astrocytic
      hamartoma.

PMID- 25389877
TI  - Unusual rapid resolution of posttrabeculectomy exudative retinal detachment with
      only topical corticosteroid therapy in a case of nanopthalmos.
AB  - PURPOSE: The purpose of this study was to report a case of nanophthalmos with
      unusual rapid resolution of exudative retinal detachment, which had developed the
      fifth day after filtering surgery with only topical corticosteroid therapy.
      METHODS: Five days after an uncomplicated trabeculectomy for the management of
      glaucoma, the patient developed exudative retinal detachment. RESULTS: Without
      choroidal drainage and any other treatment, exudative retinal detachment started
      resolving in 2 days and disappeared in 2 weeks under only topical corticosteroid
      therapy. CONCLUSION: Topical corticoid therapy alone may be sufficient to achieve
      quick resolution of exudative retinal detachment secondary to glaucoma surgery in
      nanophthalmic eyes.

PMID- 25389878
TI  - Choroidal neovascular membrane after endoresection of choroidal melanoma.
AB  - PURPOSE: The purpose of this study was to report two cases with choroidal
      melanoma who underwent endoresection and developed choroidal neovascular membrane
      (CNVM) during follow-up. METHODS: An interventional case series. RESULTS: A 62
      year-old man with choroidal melanoma in his left eye was treated with
      endoresection with pars plana vitrectomy followed by radioactive ruthenium plaque
      radiotherapy. Thirteen months after the surgery, the patient developed a CNVM at
      the superior edge of the surgical excision site and was treated with argon laser
      photocoagulation. Twenty-eight months after laser photocoagulation, the patient
      was alive with no sign of CNVM recurrence. A 59-year-old man with choroidal
      melanoma in his left eye underwent endoresection with pars plana vitrectomy
      followed by radioactive ruthenium plaque radiotherapy. Twenty-one months later,
      he developed a CNVM, which was treated by photodynamic therapy. After 45 months
      of follow-up after photodynamic therapy, the patient had no sign of recurrent
      CNVM. CONCLUSION: Choroidal neovascular membrane is a rare complication after
      endoresection of choroidal melanoma. Being aware of this risk leads to early
      diagnosis and prompt treatment that can prevent deterioration of vision.

PMID- 25389879
TI  - Bilateral orbital vasculature alterations after systemic chemotherapy and
      external beam radiation therapy treatment of advanced retinoblastoma:
      implications for intraarterial chemotherapy management.
AB  - PURPOSE: The purpose of this study was to report significant alterations in
      orbital vasculature after combined systemic chemoreduction with consolidating
      external beam radiotherapy treatment in a case of advanced retinoblastoma and to
      discuss implications for intraarterial melphalan rescue chemotherapy. METHODS: We
      studied the case of a 22-month-old child who had been treated recently with
      intraarterial melphalan perfusion after multimodal therapy for advanced
      intraocular retinoblastoma. RESULTS: Orbital angiography of both eyes, performed
      before the intraarterial melphalan injection, documented an atypical attenuated
      orbital vasculature. The right ophthalmic artery angiogram showed loss of a
      normal dominant central retinal artery. Instead, multiple dysplastic angiogenic
      vessels from the ophthalmic artery were found to supply the retina. A single long
      ciliary artery was noted with collateral vessels supplying the anterior globe.
      The left ophthalmic artery angiogram showed a stenotic artery with minimal
      anterograde flow. CONCLUSION: Orbital vasculature may be impacted by combined
      systemic chemotherapy and external beam radiation therapy. These changes need to
      be considered in the use of intraarterial melphalan for the treatment of patients
      with advanced retinoblastoma.

PMID- 25389880
TI  - Roller coaster-associated retinal detachments.
AB  - PURPOSE: The purpose of this study was to report two cases of rhegmatogenous
      retinal detachment noted immediately after roller coaster riding in an at-risk
      population. METHODS: In separate incidents, a 35-year-old woman and a 45-year-old
      woman, both significantly myopic, presented with visual symptoms after riding
      roller coasters. RESULTS: Both patients were found to have acute rhegmatogenous
      retinal detachments associated with myopic degenerative changes. The pathology
      supported an acute, traumatic etiology for the detachments. CONCLUSION: Roller
      coaster riding should be considered an adjunct risk factor for retinal detachment
      in predisposed patients.

PMID- 25389881
TI  - Vitreous hemorrhage after whole-body vibration training.
AB  - PURPOSE: The purpose of this study was to describe spontaneous vitreous
      hemorrhage after a session of whole-body vibration training. METHOD: This is a
      case report of a 52-year-old man with no ophthalmic history who presented with a
      uniocular drop in vision. RESULTS: Examination showed two areas of vitreous
      condensations associated with vitreous hemorrhage. Localized posterior vitreous
      detachment was confirmed on B-scan ultrasound. No retinal breaks were identified.
      CONCLUSION: The effects of whole-body vibration training have been well
      documented previously and parallels can be drawn with the effects of pneumatic
      drilling. Only one previous case of vitreous hemorrhage after whole-body
      vibration has been reported, and the authors urge vigilance in reporting this
      suspected association.

PMID- 25389882
TI  - Successful treatment of choroidal neovascularization secondary to sorsby fundus
      dystrophy with intravitreal bevacizumab.
AB  - PURPOSE: The purpose of this study was to investigate the response of choroidal
      neovascularization (CNV) in Sorsby fundus dystrophy to intravitreal bevacizumab.
      METHODS: Three eyes of 2 patients with CNV as a result of Sorsby fundus dystrophy
      were treated with intravitreal bevacizumab injections (0.05 mL, 1.25 mg
      bevacizumab). Best-corrected visual acuity, optical coherence tomography, and/or
      fluorescein angiography before and after treatment were assessed. RESULTS: At 33
      month follow-up, after 6 intravitreal bevacizumab injections in 1 eye of the
      first patient, best-corrected visual acuity improved from 1.00 logarithm of the
      minimum angle of resolution to 0.93 logarithm of the minimum angle of resolution;
      there was no evidence of CNV activity on optical coherence tomography or on
      fluorescein angiography. At 6 weeks after 1 injection in the first patient's
      fellow eye, best-corrected visual acuity was stabilized at 0.00 logarithm of the
      minimum angle of resolution without any CNV activity on optical coherence
      tomography or on fluorescein angiography. At 12-week follow-up, after 1
      intravitreal bevacizumab injection in 1 eye of the second patient, best-corrected
      visual acuity improved from 1.00 logarithm of the minimum angle of resolution to
      0.00 logarithm of the minimum angle of resolution; there was no evidence of CNV
      activity on optical coherence tomography or on fluorescein angiography.
      CONCLUSION: Intravitreal bevacizumab should be considered as a safe and effective
      treatment for CNV secondary to Sorsby fundus dystrophy.

PMID- 25389883
TI  - Spectral-domain optical coherence tomography of endogenous fungal
      endophthalmitis.
AB  - PURPOSE: The purpose of this study is to report the use of spectral-domain
      optical coherence tomography in monitoring endogenous Candida endophthalmitis.
      METHODS: A patient diagnosed with candidemia was followed for endogenous Candida
      endophthalmitis. With each clinic visit, the patient underwent visual acuity
      assessment, slit-lamp biomicroscopy, dilated fundus examination, color fundus
      photography, spectral-domain optical coherence tomography, and fluorescein
      angiography. RESULTS: At initial examination, the patient's visual acuity was
      20/200 in both eyes. Creamy yellow fungal lesions were visualized within one disk
      diameter of the fovea and along the arcades. These lesions, in various stages of
      evolution, were imaged with spectral-domain optical coherence tomography,
      localizing their depth within the retina. Deeper retinal lesions corresponded to
      early active inflammatory lesions as confirmed by hypofluorescent areas with late
      staining on the fluorescein angiography. More superficial lesions on the
      vitreoretinal interface corresponded to late inactive lesions corresponding to
      blocked areas on the fluorescein angiography. After the resolution of most
      lesions, her final visual acuity was 20/25 in both eyes at last follow-up.
      CONCLUSION: The depth of lesions as shown by the spectral-domain optical
      coherence tomography corresponds to various stages of fungal infection, allowing
      clinicians to monitor the disease and its response to therapy.

PMID- 25389884
TI  - Intrauterine injury simulating abusive head trauma.
AB  - PURPOSE: The purpose of this study was to describe a patient with intrauterine
      injury simulating abusive head trauma and its management. METHODS: A case report
      of a premature infant born at 35 weeks 2 days through an uncomplicated vaginal
      delivery was found to have cerebral hemorrhages on magnetic resonance imaging
      after presenting with respiratory distress. The infant was referred to us for
      bilateral subconjunctival hemorrhages and periorbital edema. We performed serial
      ophthalmologic examinations, reviewed all prenatal history with the mother of the
      infant, and reviewed all relevant hospital notes, laboratory results, and imaging
      results. RESULTS: On ophthalmologic examination, the patient was found to have
      vitreous and retinal hemorrhages bilaterally. Prenatal history showed
      intrauterine trauma inflicted by the mother in the setting of an atraumatic
      delivery. The patient required bilateral vitrectomies to prevent amblyopia.
      CONCLUSION: Intrauterine injury may simulate abusive head trauma, and it is
      important for clinicians to recognize this presentation to prevent further harm
      to the infant and prevent devastating visual loss.

PMID- 25389885
TI  - Pseudoduplication of the optic disk.
AB  - PURPOSE: The purpose of this study was to report a case of a chorioretinal
      coloboma mimicking a second optic disk in an asymptomatic 12-year-old boy.
      METHODS: This is a case report. RESULTS: An asymptomatic 12-year-old boy
      presented with a chorioretinal coloboma of the right eye giving the impression of
      a second optic disk. The patient also had a superior visual field defect.
      CONCLUSION: True optic nerve duplication is a rare entity that can be mimicked by
      other etiologies, including choroidal colobomas and postinflammatory lesions,
      requiring careful examination by clinicians.

PMID- 25389886
TI  - Peripapillary staphyloma with associated retinopathy of prematurity.
AB  - PURPOSE: To report a case of asymmetric retinopathy of prematurity associated
      with a peripapillary staphyloma. METHODS: Case report. RESULTS: A 1,545-g male
      infant was born at 34 weeks' gestation. He was noted on initial examination to
      have a peripapillary staphyloma in the left eye and immature retinal vasculature
      in zone 2 of both eyes. Follow-up examination at 16 weeks of age showed a normal
      right eye with full vascularization and zone 2, stage 2 retinopathy of
      prematurity in the left eye. CONCLUSION: To our knowledge, this is the first
      reported case of peripapillary staphyloma in which only the affected eye
      developed retinopathy of prematurity.

PMID- 25389887
TI  - Macular hole formation after intravitreal bevacizumab administration in a patient
      with myopic choroidal neovascularization.
AB  - PURPOSE: The purpose of this study was to report a case of macular hole formation
      in a patient with myopic choroidal neovascularization (CNV), who was administered
      intravitreal bevacizumab. METHODS: A 55-year-old woman with high myopia presented
      with a sudden decrease in vision in her right eye. Optical coherence tomography
      imaging showed subfoveal type 2 CNV and a preretinal structure with vitreomacular
      traction. The patient received intravitreal bevacizumab treatment for the CNV.
      RESULTS: Four weeks after the second intravitreal bevacizumab injection,
      regression of CNV and formation of a macular hole were confirmed from the
      findings of the optical coherence tomography image. The patient was followed up
      without further treatment. Six months after the second intravitreal bevacizumab
      injection, the macular hole closed spontaneously, and visual acuity improved in
      her right eye. CONCLUSION: Intravitreal bevacizumab is a powerful modality in the
      management of myopic CNV; however, the possibility of infrequent complication
      should be considered.

PMID- 25389888
TI  - Idiopathic bilateral retinal dialyses complicated by posterior retinal tear after
      blunt trauma.
AB  - PURPOSE: The purpose of this study was to present a case of posterior rupture in
      a previously detached retina after blunt trauma. METHOD: This is a case report.
      RESULT: A child with idiopathic bilateral retinal dialyzes sustained accidental
      blunt trauma to the left eye while awaiting surgery. This caused a posterior
      rupture of the retina in an already preexisting retinal detachment. The right eye
      underwent uneventful cryopexy and a buckle procedure. The left eye was managed
      conservatively while awaiting spontaneous posterior vitreous separation.
      Unfortunately, the retina detached further to involve the macula with progression
      of proliferative vitreoretinopathy. The child required three subsequent
      vitrectomies in the left eye to stabilize the retina. CONCLUSION: This case
      highlights the etiology of retinal dialyzes and the dilemmas in the management of
      complicated retinal detachment.

PMID- 25389889
TI  - Familial retinal arteriolar tortuosity associated with retinal and vitreous
      hemorrhages.
AB  - PURPOSE: The purpose of this study was to report a patient with familial retinal
      arteriolar tortuosity who presented with both retinal and vitreous hemorrhages.
      METHODS: This was a single case report. RESULTS: A young woman affected by severe
      spina bifida with myelomeningocele and hydrocephalus presented with a 4-month
      history of blurred vision in both eyes. The patient had a history of severe
      constipation. Fundus examination of both eyes showed tortuosity of the retinal
      arterioles and multiple hemorrhages throughout the fundus at the sub-,
      intraretinal, subhyaloid, and intravitreal levels. The bleeding was likely
      because of a Valsalva effect. CONCLUSION: Familial retinal arteriolar tortuosity
      is a rare disease characterized by the selective tortuosity of the second- and
      third-order retinal arterioles in the macula and peripapillary area. Patients may
      experience episodes of vision loss secondary to retinal hemorrhages. To our
      knowledge, this is the first report of vitreous hemorrhage in a patient with
      familial retinal arteriolar tortuosity.

PMID- 25389890
TI  - Spontaneous bilateral subhyaloid hemorrhage in congenital hypofibrinogenemia.
AB  - PURPOSE: The purpose of this study was to report a case of spontaneous bilateral
      subhyaloid hemorrhage in congenital hypofibrinogenemia. METHODS: This is a single
      case report. A 14-year-old girl presented with a spontaneous bilateral decrease
      in vision. Her history was unremarkable. On examination, visual acuity was 20/80
      in the right eye and 20/1200 in the left eye. Fundus examination showed bilateral
      subhyaloid hemorrhage. Clotting profile showed normal activated partial
      thromboplastin time and normal prothrombin time with fibrinogen decreased to 50
      mg/dL (normal, 200-400 mg/dL). RESULTS: Therapeutic cryoprecipitate infusion was
      administered. At 3 months, visual acuity improved to 20/20 with resolution of
      subhyaloid hemorrhage in both eyes. CONCLUSION: Estimation of fibrinogen in the
      absence of other evaluated causes of blood dyscrasias would help with prompt
      diagnosis and successful management.

PMID- 25389891
TI  - Management of posteriorly dislocated endothelial keratoplasty donor lenticule.
AB  - PURPOSE: The purpose of this study was to describe the management of a
      keratoplasty lenticule adhering to the retina after intraoperative dislocation.
      METHODS: We describe the posterior dislocation of the donor lenticule during
      endothelial keratoplasty in a 72-year-old woman with a transscleraly sutured
      intraocular lens, previous pars plana vitrectomy, and a posteriorly positioned
      Ahmed glaucoma tube shunt. The lenticule was retrieved through a pars plana
      approach 2 weeks later, at which time it was tightly adherent to the extramacular
      retina. Concurrent keratoplasty was performed. RESULTS: Six months after
      retrieval of the dislocated lenticule with repeat keratoplasty, the retinal
      examination is stable and the new graft remains attached. CONCLUSION: An iris
      defect, the absence of capsular support, and a history of previous vitrectomy are
      all potential risk factors for the intraoperative migration of a keratoplasty
      lenticule. The surgical view 2 weeks after dislocation was not a limiting factor
      in the retrieval of the lenticule. However, the tight adherence of the lenticule
      to the retina required extensive peeling. To avoid a more difficult surgical
      repair and the potential for scar formation, earlier surgical repair would be
      preferable, especially if dealing with a macular location.

PMID- 25389892
TI  - Optical coherence tomography of nasal sliding of the retina and temporal arcades
      in retinopathy of prematurity.
AB  - PURPOSE: The purpose of this study was to report a case of nasal dragging and
      sliding of retina over the optic disk, as documented by spectral-domain optical
      coherence tomography. METHODS: Case report. RESULTS: We present the case of a 22
      year-old woman with a history of retinopathy of prematurity noted to have nasal
      dragging of the retina, stable at least since the patient was 21 months old.
      Spectral domain optical coherence tomography showed folding of the temporal
      retina over the disk and the adjacent nasal retina, contributing to the nasal
      diversion of the vessels within the fold. CONCLUSION: Despite retinal anchoring
      at the optic nerve, the disk does not appear to serve as a barrier to retinal
      movement. Spectral domain optical coherence tomography showed in vivo a mechanism
      through which nasal dragging can occur, namely through the sliding and folding of
      temporal retina over the disk and the adjacent nasal retina.

PMID- 25389893
TI  - Spectral domain-optical coherence tomography and fundus autofluorescence findings
      in a case of purtscher-like retinopathy.
AB  - PURPOSE: The purpose of this study is to describe spectral domain-optical
      coherence tomography and autofluorescence images in a case of bilateral Purtscher
      like retinopathy. METHODS: This is an observational case report of a 31-year-old
      man suffering with Purtscher-like retinopathy postpancreatitis. RESULTS: In the
      acute phase, spectral domain-optical coherence tomography showed
      hyperreflectivity in the inner retinal layers, corresponding to cotton-wool
      exudation as a result of precapillary ischemia. The follow-up using spectral
      domain-optical coherence tomography showed that the inner retina is the most
      involved layer by ischemic damage in the acute phase. In the regression phase,
      signs of suffering in the outer retinal layers became visible as well, although
      after the resolution of the pathology, there was no evident spectral domain
      optical coherence tomography abnormality in the photoreceptors layers.
      Autofluorescence images after resolution showed hyperautofluorescent vessels
      affected by ischemia as a possible result of long-lasting retention of
      intraretinal blood. CONCLUSION: Spectral domain-optical coherence tomography and
      autofluorescence are sensitive and noninvasive imaging modalities to evaluate
      retinal alterations after Purtscher-like retinopathy. Spectral domain-optical
      coherence tomography confirms that ischemia causes an alteration primarily in the
      inner retinal layers, but the process also involves the outer retinal layers.

PMID- 25389894
TI  - New treatments in radiation retinopathy.
AB  - PURPOSE: The purpose of this study was to present a case of radiation retinopathy
      and review of the literature on treatment options for the disease. METHODS: A 28
      year-old woman presented with bilateral visual acuity impairment. Four years
      before presentation, she was diagnosed with Hodgkin lymphoma affecting the left
      supraclavicular area and was treated with chemotherapy and radiotherapy,
      achieving complete remission. Bilateral radiation retinopathy with macular edema
      was diagnosed after the possibility of relapse was ruled out. Several treatments,
      including intravitreal bevacizumab and triamcinolone, laser photocoagulation, and
      surgery, have been used in an effort to resolve the macular edema and the
      tractional proliferative retinopathy. RESULT: Radiation tractional retinopathy
      was controlled with surgery and photocoagulation, and macular edema was resolved
      with a final visual acuity of 20/25 in both eyes. CONCLUSION: Radiation
      retinopathy is a complication that is devastating to the visual pathway.
      Historically, it has been refractory to treatment, but new options are now
      available. We review the most recent literature on radiation retinopathy
      treatment.

PMID- 25389895
TI  - Intravitreal ranibizumab in the treatment of fungal endophthalmitis scar-related
      choroidal neovascular membrane.
AB  - PURPOSE: The purpose of this study was to report the efficacious use of
      intravitreal ranibizumab in the management of postfungal endophthalmitis scar
      related choroidal neovascular membrane. METHODS: This is an interventional case
      report. RESULTS: The patient's visual acuity was stabilized and membrane activity
      ceased after treatment with three injections of intravitreal ranibizumab at
      monthly intervals. CONCLUSION: Intravitreal ranibizumab can be useful in the
      treatment of inflammatory scar-related choroidal neovascular membrane.

PMID- 25389896
TI  - Correspondence.

PMID- 25389897
TI  - Exercise-trained men and women: role of exercise and diet on appetite and energy
      intake.
AB  - The regulation of appetite and energy intake is influenced by numerous hormonal
      and neural signals, including feedback from changes in diet and exercise.
      Exercise can suppress subjective appetite ratings, subsequent energy intake, and
      alter appetite-regulating hormones, including ghrelin, peptide YY, and glucagon
      like peptide 1(GLP-1) for a period of time post-exercise. Discrepancies in the
      degree of appetite suppression with exercise may be dependent on subject
      characteristics (e.g., body fatness, fitness level, age or sex) and exercise
      duration, intensity, type and mode. Following an acute bout of exercise, exercise
      trained males experience appetite suppression, while data in exercise-trained
      women are limited and equivocal. Diet can also impact appetite, with low-energy
      dense diets eliciting a greater sense of fullness at a lower energy intake. To
      date, little research has examined the combined interaction of exercise and diet
      on appetite and energy intake. This review focuses on exercise-trained men and
      women and examines the impact of exercise on hormonal regulation of appetite,
      post-exercise energy intake, and subjective and objective measurements of
      appetite. The impact that low-energy dense diets have on appetite and energy
      intake are also addressed. Finally, the combined effects of high-intensity
      exercise and low-energy dense diets are examined. This research is in exercise
      trained women who are often concerned with weight and body image issues and
      consume low-energy dense foods to keep energy intakes low. Unfortunately, these
      low-energy intakes can have negative health consequences when combined with high
      levels of exercise. More research is needed examining the combined effect of diet
      and exercise on appetite regulation in fit, exercise-trained individuals. 

PMID- 25389898
TI  - Dietary flavonoids and gastric cancer risk in a Korean population.
AB  - Gastric cancer is the most common cancer among men in Korea, and dietary factors
      are closely associated with gastric cancer risk. We performed a case-control
      study using 334 cases and 334 matched controls aged 35-75 years. Significant
      associations were observed in total dietary flavonoids and their subclasses, with
      the exception of anthocyanidins and isoflavones (OR (95% CI): 0.49 (0.31-0.76), p
      trend = 0.007 for total flavonoids). However, these associations were not
      significant after further adjustment for fruits and vegetable consumption (OR
      (95% CI): 0.62 (0.36-1.09), p trend = 0.458 for total flavonoids). Total
      flavonoids and their subclasses, except for isoflavones, were significantly
      associated with a reduced risk gastric cancer in women (OR (95% CI): 0.33 (0.15
      0.73), p trend = 0.001 for total flavonoids) but not in men (OR (95% CI): 0.70
      (0.39-1.24), p trend = 0.393 for total flavonoids). A significant inverse
      association with gastric cancer risk was observed in flavones, even after
      additional adjustment for fruits and vegetable consumption in women. No
      significantly different effects of flavonoids were observed between H. pylori
      positive and negative subjects. In conclusion, dietary flavonoids were inversely
      associated with gastric cancer risk, and these protective effects of dietary
      flavonoids were prominent in women. No clear differences were observed in the
      subgroup analysis of H. pylori and smoking status. 

PMID- 25389899
TI  - Annatto tocotrienol improves indices of bone static histomorphometry in
      osteoporosis due to testosterone deficiency in rats.
AB  - This study aimed to evaluate the effects of annatto tocotrienol on indices of
      bone static histomorphometry in orchidectomized rats. Forty male rats were
      randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto
      tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL
      group was sacrificed upon receipt. All rats except the SH group underwent
      bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was
      administered orally daily to the AnTT group for eight weeks. Testosterone
      enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for
      eight weeks to the TE group. The rat femurs were collected for static
      histomorphometric analysis upon necropsy. The results indicated that the ORX
      group had significantly higher osteoclast surface and eroded surface, and
      significantly lower osteoblast surface, osteoid surface and osteoid volume
      compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone
      enanthate intervention prevented all these changes (p < 0.05). The efficacy of
      annatto tocotrienol was on par with testosterone enanthate. In conclusion,
      annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling
      caused by increased osteoclast and bone resorption, and decreased osteoblast and
      bone formation. This serves as a basis for the application of annatto tocotrienol
      in hypogonadal men as an antiosteoporotic agent. 

PMID- 25389901
TI  - The influence of dietary fat on liver fat accumulation.
AB  - Obesity is a known risk factor for the development of non-alcoholic fatty liver
      disease (NAFLD); however, it has been suggested that dietary fat, both amount and
      composition, may play a pivotal role in its development, independent of body
      fatness. Studies that have investigated the role of dietary fat on liver fat
      accumulation are reasonably sparse. We review here the available work that has
      investigated the impact of dietary fat: amount, composition and frequency, on
      liver fat accumulation in human observational and intervention studies. Overall,
      it would seem that total calorie consumption, rather than dietary fat
      composition, is an important factor in the development of fatty liver disease in
      humans. 

PMID- 25389902
TI  - Multigenerational genomic responses to dietary phosphorus and temperature in
      Daphnia.
AB  - Temperature and nutrient availability are both hypothesized to affect organisms
      at the cellular and genomic levels. In this multigenerational study, Daphnia
      magna (D. magna) and Daphnia pulex (D. pulex) were maintained at high (20 
      degrees C) and low (10  degrees C) temperatures and nourished with phosphorus (P)
      sufficient (50 MUmol/L) and P-deficient (2 MUmol/L) algae for up to 35
      generations to assess the multigenerational impacts on genome size and nucleus
      size. Analysis by flow cytometry revealed significant increases in nucleus size
      for both species as well as genome size for D. magna in response to a low
      temperature. The degree of endoreplication, measured as cycle value, was species
      specific and responded to temperature and dietary composition. Under dietary P
      deficiency, D. magna, but not D. pulex, showed an apparent reduction in haploid
      genome size (C-value). These genomic responses are unlikely to reflect
      differences in nucleotide numbers, but rather structural changes affecting
      fluorochrome binding. While the ultimate and proximate causes of these responses
      are unknown, they suggest an intriguing potential for genomic responses that
      merits further research. 

PMID- 25389900
TI  - Vitamin a deficiency and alterations in the extracellular matrix.
AB  - Vitamin A or retinol which is the natural precursor of several biologically
      active metabolites can be considered the most multifunctional vitamin in mammals.
      Its deficiency is currently, along with protein malnutrition, the most serious
      and common nutritional disorder worldwide. It is necessary for normal embryonic
      development and postnatal tissue homeostasis, and exerts important effects on
      cell proliferation, differentiation and apoptosis. These actions are produced
      mainly by regulating the expression of a variety of proteins through
      transcriptional and non-transcriptional mechanisms. Extracellular matrix proteins
      are among those whose synthesis is known to be modulated by vitamin A. Retinoic
      acid, the main biologically active form of vitamin A, influences the expression
      of collagens, laminins, entactin, fibronectin, elastin and proteoglycans, which
      are the major components of the extracellular matrix. Consequently, the structure
      and macromolecular composition of this extracellular compartment is profoundly
      altered as a result of vitamin A deficiency. As cell behavior, differentiation
      and apoptosis, and tissue mechanics are influenced by the extracellular matrix,
      its modifications potentially compromise organ function and may lead to disease.
      This review focuses on the effects of lack of vitamin A in the extracellular
      matrix of several organs and discusses possible molecular mechanisms and
      pathologic implications. 

PMID- 25389904
TI  - Fenofibrate enhances barrier function of endothelial continuum within the
      metastatic niche of prostate cancer cells.
AB  - OBJECTIVE: Extravasation of circulating cancer cells is an important step of the
      metastatic cascade and a potential target for anti-cancer strategies based on
      vasoprotective drugs. Reports on anti-cancer effects of fenofibrate (FF) prompted
      us to analyze its influence on the endothelial barrier function during prostate
      cancer cell diapedesis. RESEARCH DESIGN AND METHODS: In vitro co-cultures of
      endothelial cells with cancer cells imitate the 'metastatic niche' in vivo. We
      qualitatively and quantitatively estimated the effect of 25 MUM FF on the events
      which accompany prostate carcinoma cell diapedesis, with the special emphasis on
      endothelial cell mobilization. RESULTS: Fenofibrate attenuated cancer cell
      diapedesis via augmenting endothelial cell adhesion to the substratum rather than
      through the effect on intercellular communication networks within the metastatic
      niche. The inhibition of endothelial cell motility was accompanied by the
      activation of PPARalpha-dependent and PPARalpha-independent reactive oxygen
      species signaling, Akt and focal adhesion kinase (FAK) phosphorylation, in the
      absence of cytotoxic effects in endothelial cells. CONCLUSIONS: Fenofibrate
      reduces endothelial cell susceptibility to the paracrine signals received from
      prostate carcinoma cells, thus inhibiting endothelial cell mobilization and
      reducing paracellular permeability of endothelium in the metastatic niche. Our
      data provide a mechanistic rationale for extending the clinical use of FF and for
      the combination of this well tolerated vasoactive drug with the existing
      multidrug regimens used in prostate cancer therapy.

PMID- 25389903
TI  - A relationship between the transient structure in the monomeric state and the
      aggregation propensities of alpha-synuclein and beta-synuclein.
AB  - alpha-Synuclein is an intrinsically disordered protein whose aggregation is
      implicated in Parkinson's disease. A second member of the synuclein family, beta
      synuclein, shares significant sequence similarity with alpha-synuclein but is
      much more resistant to aggregation. beta-Synuclein is missing an 11-residue
      stretch in the central non-beta-amyloid component region that forms the core of
      alpha-synuclein amyloid fibrils, yet insertion of these residues into beta
      synuclein to produce the betaSHC construct does not markedly increase the
      aggregation propensity. To investigate the structural basis of these different
      behaviors, quantitative nuclear magnetic resonance data, in the form of
      paramagnetic relaxation enhancement-derived interatomic distances, are combined
      with molecular dynamics simulations to generate ensembles of structures
      representative of the solution states of alpha-synuclein, beta-synuclein, and
      betaSHC. Comparison of these ensembles reveals that the differing aggregation
      propensities of alpha-synuclein and beta-synuclein are associated with
      differences in the degree of residual structure in the C-terminus coupled to the
      shorter separation between the N- and C-termini in beta-synuclein and betaSHC,
      making protective intramolecular contacts more likely. 

PMID- 25389905
TI  - Acupuncture-related modulation of pain-associated brain networks during
      electrical pain stimulation: a functional magnetic resonance imaging study.
AB  - OBJECTIVE: Findings of existing functional MRI (fMRI) studies on the neural
      mechanisms that mediate effects of acupuncture analgesia are inconsistent. This
      study analyzes the effects of manual acupuncture on pain ratings and brain
      activation in response to experimental, electrical pain stimuli. DESIGN: Fourteen
      healthy volunteers were examined by using a 1.5-T MRI scanner. The intensity of
      pain stimuli was adjusted to individual pain ratings on a numeric rating scale.
      Baseline fMRI was performed during electrical pain stimulation in a blocked
      design. For the second session, manual acupuncture with repeated stimulation was
      performed on contralateral acupoints-large intestine 4, liver 3, and stomach 36
      before imaging. After imaging, subjective pain ratings and ratings of the de qi
      sensation were assessed. RESULTS: Compared with baseline, volunteers showed
      modulated brain activity under pain conditions in the cingulate gyrus, insula,
      primary somatosensory cortex, and prefrontal areas after the acupuncture session.
      In accordance with the literature, anterior insular and prefrontal activity
      seemed to be correlated with acupuncture treatment. CONCLUSION: This study
      supports the existence of analgesic acupuncture effects that outlast the needling
      period. Pain-associated brain areas were modulated in direct response to a
      preceding acupuncture treatment.

PMID- 25389907
TI  - Functional connectivity analyses using emulated and conventional resting-state
      data: parts versus the whole story.
AB  - Continuous resting-state (RS) functional magnetic resonance imaging (fMRI) has
      become particularly useful to identify changes in functional connectivity (FC) in
      CNS disorders. Fair et al. proposed a method of volume extraction to emulate RS
      fMRI from block-design experiments. Whether the validity of this approach holds
      true in multiple sclerosis (MS) patients has not been tested formally so far.
      Twelve MS patients and 18 controls underwent conventional RS fMRI and a cognitive
      block-design fMRI. The total amount of volumes as well as the truncated set of
      volumes of both functional datasets was separately analyzed using a seed-based
      approach. Overall, seed-based analyses of FC from the anterior cingulated cortex
      allowed identification of the same key-network constituents using different
      analytical approaches, whereas higher-level within-group analyses of emulated RS
      versus continuous RS also revealed significant distinct differences in FC
      networks. Using the emulated RS approach, a general identification of
      connectivity networks similar to those obtained using conventional RS data also
      appears feasible in diseased brains. Higher-level contrasts, however, yielded
      different results attesting to a significant impact of employed methodology.

PMID- 25389908
TI  - Exploring the ActiLife((r)) filtration algorithm: converting raw acceleration
      data to counts.
AB  - Though portable accelerometers are ubiquitous in physiology and public health
      studies, their accuracy as objective measures of physical activity is still being
      examined. This paper enumerates and analyzes the various biases of the widely
      used ActiLife((r)) software in reporting activity counts from ActiGraph((r))
      accelerometers. In particular, we focus on the two-stage proprietary filtration
      algorithm used to convert raw acceleration data, for a sampling rate of 30 Hz, to
      compressed 1 Hz signals; we develop simple novel methods to analyze the action of
      the software filter on the raw data in the frequency domain.

PMID- 25389906
TI  - Extensive phenotyping of individuals at risk for familial interstitial pneumonia
      reveals clues to the pathogenesis of interstitial lung disease.
AB  - RATIONALE: Asymptomatic relatives of patients with familial interstitial
      pneumonia (FIP), the inherited form of idiopathic interstitial pneumonia, carry
      increased risk for developing interstitial lung disease. OBJECTIVES: Studying
      these at-risk individuals provides a unique opportunity to investigate early
      stages of FIP pathogenesis and develop predictive models of disease onset.
      METHODS: Seventy-five asymptomatic first-degree relatives of FIP patients (mean
      age, 50.8 yr) underwent blood sampling and high-resolution chest computed
      tomography (HRCT) scanning in an ongoing cohort study; 72 consented to
      bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies.
      Twenty-seven healthy individuals were used as control subjects. MEASUREMENTS AND
      MAIN RESULTS: Eleven of 75 at-risk subjects (14%) had evidence of interstitial
      changes by HRCT, whereas 35.2% had abnormalities on transbronchial biopsies. No
      differences were noted in inflammatory cells in BAL between at-risk individuals
      and control subjects. At-risk subjects had increased herpesvirus DNA in cell-free
      BAL and evidence of herpesvirus antigen expression in alveolar epithelial cells
      (AECs), which correlated with expression of endoplasmic reticulum stress markers
      in AECs. Peripheral blood mononuclear cell and AEC telomere length were shorter
      in at-risk individuals than healthy control subjects. The minor allele frequency
      of the Muc5B rs35705950 promoter polymorphism was increased in at-risk subjects.
      Levels of several plasma biomarkers differed between at-risk subjects and control
      subjects, and correlated with abnormal HRCT scans. CONCLUSIONS: Evidence of lung
      parenchymal remodeling and epithelial dysfunction was identified in asymptomatic
      individuals at risk for FIP. Together, these findings offer new insights into the
      early pathogenesis of idiopathic interstitial pneumonia and provide an ongoing
      opportunity to characterize presymptomatic abnormalities that predict progression
      to clinical disease.

PMID- 25389909
TI  - In vitro and mouse studies supporting therapeutic utility of triiodothyroacetic
      acid in MCT8 deficiency.
AB  - Monocarboxylate transporter 8 (MCT8) transports thyroid hormone (TH) across the
      plasma membrane. Mutations in MCT8 result in the Allan-Herndon-Dudley syndrome,
      comprising severe psychomotor retardation and elevated serum T3 levels. Because
      the neurological symptoms are most likely caused by a lack of TH transport into
      the central nervous system, the administration of a TH analog that does not
      require MCT8 for cellular uptake may represent a therapeutic strategy. Here, we
      investigated the therapeutic potential of the biologically active T3 metabolite
      Triac (TA3) by studying TA3 transport, metabolism, and action both in vitro and
      in vivo. Incubation of SH-SY5Y neuroblastoma cells and MO3.13 oligodendrocytes
      with labeled substrates showed a time-dependent uptake of T3 and TA3. In intact
      SH-SY5Y cells, both T3 and TA3 were degraded by endogenous type 3 deiodinase, and
      they influenced gene expression to a similar extent. Fibroblasts from MCT8
      patients showed an impaired T3 uptake compared with controls, whereas TA3 uptake
      was similar in patient and control fibroblasts. In transfected cells, TA3 did not
      show significant transport by MCT8. Most importantly, treatment of athyroid Pax8
      knockout mice and Mct8/Oatp1c1-double knockout mice between postnatal days 1 and
      12 with TA3 restored T3-dependent neural differentiation in the cerebral and
      cerebellar cortex, indicating that TA3 can replace T3 in promoting brain
      development. In conclusion, we demonstrated uptake of TA3 in neuronal cells and
      in fibroblasts of MCT8 patients and similar gene responses to T3 and TA3. This
      indicates that TA3 bypasses MCT8 and may be used to improve the neural status of
      MCT8 patients. 

PMID- 25389911
TI  - Potential role of granulocyte-monocyte colony-stimulating factor in the
      progression of intracranial aneurysms.
AB  - Macrophages play a central role in the inflammatory response leading to aneurysm
      formation, progression, and rupture. The purpose of this study was to determine
      whether granulocyte-monocyte colony-stimulating factor (GM-CSF) plays a role in
      the progression of human intracranial aneurysms. Specifically, we investigated
      whether there was a correlation between the aneurysm size and the concentration
      of GM-CSF in the lumen of intracranial aneurysms. The concentrations of GM-CSF in
      blood samples drawn from the lumen of 15 human unruptured saccular intracranial
      aneurysms of 14 consecutive patients were compared. The aneurysm size was 10.3+/
      9 mm on average. The mean plasma concentration of GM-CSF was 27.9+/-3.1 pg/mL in
      the lumen of intracranial aneurysms. The mean plasma concentration of GM-CSF was
      significantly higher in aneurysms larger than 7 mm (30.1+/-2.8 pg/mL) compared
      with aneurysms smaller than 7 mm (26.4+/-2.4 pg/mL; p=0.02). There was a
      significant positive correlation between the aneurysm size and the plasma
      concentration of GM-CSF (Spearman's rho=0.55; p=0.04). There is a significant
      positive correlation between the aneurysm size and the plasma concentration of GM
      CSF in aneurysm lumens. This suggests that GM-CSF, through its stimulatory
      function on macrophages, may promote aneurysm progression and may be a possible
      therapeutic target. 

PMID- 25389910
TI  - Thermogenic activity of UCP1 in human white fat-derived beige adipocytes.
AB  - Heat-producing beige/brite (brown-in-white) adipocytes in white adipose tissue
      have the potential to suppress metabolic disease in mice and hold great promise
      for the treatment of obesity and type 2 diabetes in humans. Here, we demonstrate
      that human adipose-derived stromal/progenitor cells (hASCs) from subcutaneous
      white adipose tissue can be efficiently converted into beige adipocytes. Upon
      pharmacological activation of peroxisome proliferator-activated receptor-gamma,
      hASC-derived adipocytes activated beige fat-selective genes and a brown/beige fat
      selective electron transport chain gene program. Importantly, hASC-derived beige
      fat cells displayed the bioenergetic characteristics of genuine brown fat cells,
      including a capacity for increased respiratory uncoupling in response to beta
      adrenergic agonists. Furthermore, knock-down experiments reveal that the
      thermogenic capacity of human beige fat cells was entirely dependent on the
      presence of Uncoupling protein 1. In summary, this study reveals that hASCs can
      be readily differentiated into beige adipocytes that, upon activation, undergo
      uncoupling protein 1-dependent thermogenesis. 

PMID- 25389912
TI  - Surveying the knowledge, attitudes, and practices of District of Columbia ACOG
      members related to breastfeeding.
AB  - Although the American Academy of Pediatrics and the American Congress of
      Obstetricians and Gynecologists (ACOG) recommend exclusive breastfeeding for the
      first 6 months, only 14.6% of babies born in the District of Columbia (DC)
      reached this goal. Breastfeeding support from providers has been shown to
      increase exclusive breastfeeding. We aim (1) to describe breastfeeding knowledge
      and attitudes, (2) to determine the presence of breastfeeding in routine prenatal
      discussions, and (3) to determine the knowledge of facility adoption of the
      Perinatal Care (PC) Core Measure Set among DC ACOG members. A survey sent to DC
      ACOG members assessed knowledge, attitudes, and practices related to
      breastfeeding and evaluated participants' barriers to breastfeeding counseling,
      management of breastfeeding challenges, and awareness of facility adoption of the
      PC Core Measure Set. All 29 respondents reported breastfeeding as the best infant
      nutrition and that physicians should encourage breastfeeding. However, despite
      75% reporting counseling most of their patients regarding breastfeeding, only 27%
      reported that most of their patients were breastfeeding at the postpartum visit.
      Participants scored 83% correct on knowledge-based questions. Perceived barriers
      to breastfeeding counseling included lack of time (66%), reimbursement (10%), and
      competence in managing breastfeeding problems (7%). Most respondents were unsure
      of both adoption of, and breastfeeding data collection for, the PC Core Measure
      Set (52% and 55%, respectively). Participants had knowledge gaps and identified
      barriers to discussing breastfeeding. There was limited awareness of hospital
      data collection about breastfeeding. These results indicate a need for more
      breastfeeding education among DC obstetricians-gynecologists and better outreach
      about the PC Core Measure Set. 

PMID- 25389913
TI  - A Novel Ultrasound-Based Carotid Plaque Risk Index Associated with the Presence
      of Cerebrovascular Symptoms.
AB  - PURPOSE: The purpose of this study was to determine the efficacy of a novel
      ultrasound-based carotid plaque risk index (CPRI) in predicting the presence of
      cerebrovascular symptoms in patients with carotid artery stenosis. MATERIALS AND
      METHODS: This was a cross-sectional, observational study involving 56 patients
      (mean age 76.6 years, 62.5 % male). Plaque grayscale median (GSM) and surface
      irregularity indices (SII) were measured in 82 stenosed carotid arteries (range
      10 - 95 %) and combined with the degree of stenosis (DOS) in the form of
      (DOS*SII)/(1 + GSM). A reduced index DOS/(1 + GSM) not incorporating plaque
      surface irregularities was also investigated. Receiver operating characteristic
      curves (ROC) were used to study the diagnostic efficacy of CPRI, comparing
      against DOS and an equivalent risk index constructed using a conventional
      logistic regression based method with model parameters optimized to the dataset
      (CPRIlogistic). RESULTS: There were 42 stenosed carotid arteries with
      cerebrovascular symptoms, and 40 without symptoms. The presence of symptoms
      significantly correlated with DOS, GSM and SII (p < 0.01). The median CPRI of the
      symptomatic (asymptomatic) groups were 23.2 (9.2) compared with 0.71 (0.30) for
      CPRIlogistic (p < 0.01). The diagnostic performance of CPRI exceeded that of
      CPRIlogistic and DOS, and demonstrated a better separation of the symptomatic and
      asymptomatic groups. CONCLUSION: Our novel risk index combines quantitative
      measures of carotid plaque echogenicity and surface irregularities with the
      degree of stenosis. It is a better predictor of cerebrovascular symptoms than the
      degree of stenosis and could be valuable in studies and clinical trials aimed at
      identifying vulnerable carotid artery stenoses.

PMID- 25389914
TI  - Ultrasound-Guided Percutaneous Radiofrequency Lesioning When Treating
      Recalcitrant Plantar Fasciitis: Clinical Results.
AB  - PURPOSE: We evaluated the effects of ultrasound (US)-guided percutaneous
      radiofrequency thermal lesioning (RTL) and the impact of obesity when treating
      patients with recalcitrant plantar fasciitis. MATERIALS AND METHODS: 30
      consecutive patients were enrolled. The visual analog scale (VAS), American
      Orthopedic Foot-Ankle Society (AOFAS) Ankle-Hindfoot Score, and plantar fascia
      thickness measured using US were recorded at baseline and at follow-up 1, 3, 6,
      and 12 months after surgery under local anesthesia. RESULTS: 12 patients in the
      obese (BMI >= 30 kg/m(2)) group and 18 patients in the non-obese group. There
      were significant postoperative decreases in VAS scores and in fascial thickness,
      and an increase in the AOFAS scores (all p < 0.001). The obese group showed
      delayed pain and functional improvement within the first 3 months after the index
      procedure (p < 0.01). Significant pain reduction and functional improvement were
      apparent earlier (after 1 month, p < 0.001) in the non-obese group than in the
      obese group (after 3 months, p < 0.05). Fascia thickness was positively
      correlated with the VAS score and negatively correlated with the AOFAS score
      (both p < 0.001). CONCLUSION: US should be regarded as a useful objective tool to
      guide RTL and to monitor the effectiveness of treatment. US-guided percutaneous
      RTL for recalcitrant PF is a minimally invasive treatment option that yields
      satisfactory results. Therefore, it should at least be considered before using
      more invasive procedures. Moreover, obesity leads to delayed improvement but does
      not affect overall outcome after 12 months. Plantar fascial thickness was
      correlated with VAS and AOFAS scores.

PMID- 25389915
TI  - Asperger syndrome and schizophrenia: Overlap of self-reported autistic traits
      using the Autism-spectrum Quotient (AQ).
AB  - BACKGROUND: In clinical practice, the differential diagnosis of Asperger syndrome
      (AS) versus schizophrenia can be a challenge. Some self-report instruments-such
      as the Autism-spectrum Quotient (AQ)-have been portrayed as proxies for the
      diagnosis of AS. However, it has not been demonstrated to what extent autistic
      traits-as measured by the AQ-separate AS from schizophrenia. AIM: To examine the
      AS-schizophrenia discriminating ability of the AQ. METHOD: The AQ is a 50-item
      self-administered questionnaire (with score range 0-50) for measuring "autistic
      traits" in adults. Here, it was completed by 136 individuals: 36 with
      schizophrenic psychosis, 51 with AS and 49 non-clinical comparison cases. A
      receiver operating characteristic (ROC) analysis for the total AQ score was
      performed to examine the discriminating power of the instrument. RESULT: Both
      individuals with schizophrenia and individuals with AS scored significantly
      higher on AQ than the non-clinical group. The mean total AQ score (+/- standard
      deviation) of the AS group (26.7 +/- 8.9; range 9-44) was significantly higher
      than that of the schizophrenia group (22.7 +/- 6.2; range 10-35) (P = 0.041).
      However, when using the full Likert scale for scoring, the difference did not
      reach significance. In the ROC analysis of total AQ scores for AS versus
      schizophrenia, the area under the curve (AUC) was 0.65 (P = 0.02). CONCLUSION:
      Although mean AQ scores separated AS and schizophrenia at a group comparison
      level, significant overlap of AQ scores across the two diagnostic groups clearly
      reduces the discriminating power of the AQ in the separation of schizophrenia
      from AS.

PMID- 25389916
TI  - Effects of Aromaticity in Cations and Their Functional Groups on the Low
      Frequency Spectra and Physical Properties of Ionic Liquids.
AB  - We have critically investigated the low-frequency spectra of six ionic liquids
      (ILs) consisting of systematically different cations having benzyl moieties or
      comparable-sized saturated cyclohexylmethyl groups, by means of femtosecond Raman
      induced Kerr effect spectroscopy (fs-RIKES). The target ionic liquids are
      bis(trifluoromethylsulfonyl)amide ([NTf2](-)) salts of the 1-benzyl-3
      methylimidazolium ([BzMIm](+)), 1-benzyl-1-methylpyrrolidinium ([BzMPyrr](+)), 1
      benzylpyridinium ([BzPy](+)), 1-cyclohexylmethyl-3-methylimidazolium
      ([CHxmMIm](+)), 1-cyclohexylmethyl-1-methylpyrrolidinium ([CHxmMPyrr](+)), and 1
      cyclohexylmethylpyridinium ([CHxmPy](+)) cations. The primary purpose of this
      study is to clarify the effects of charged and neutral aromatic moieties on the
      low-frequency spectrum and bulk properties such as liquid density, surface
      tension, shear viscosity, glass transition temperature, and melting point. We
      found that ILs with benzyl groups have larger surface tensions than those with
      the same cation bearing the cyclohexylmethyl group. The trend in the glass
      transition temperatures, comparing ILs having the same side group, is pyridinium
      > imidazolium > pyrrolidinium. The effects of a single aromatic moiety on the
      shear viscosity are inconclusive, although the viscosities of the ILs with
      aromatic moieties on both the cation and the benzyl group, i.e., [BzMIm][NTf2]
      and [BzPy][NTf2], are substantially lower than those of the other ILs at room
      temperature, as a consequence of their higher fragilities. In the low-frequency
      Kerr spectra in the frequency range of approximately 0.1 to 200 cm(-1) measured
      by fs-RIKES, the ILs possessing two aromatic groups show the largest relative
      intensity of the nuclear response to the electronic response. Both the charged
      and neutral aromatic rings show signals due to the ring libration; the neutral
      one appears at a lower frequency than the charged one. The relationship between
      the first moment of the broad low-frequency spectrum band and the bulk parameter
      consisting of the square root of the surface tension divided by the liquid
      density is obeyed by the cyclohexylmethyl derivatives whether the cation is
      aromatic or not, but not by the ILs with the neutral aromatic benzyl group.
      Quantum chemistry calculations have been also performed to understand the
      vibrational modes of the ionic species in the ILs. 

PMID- 25389917
TI  - Vincristine and Dactinomycin in Infantile Myofibromatosis With a Review of
      Treatment Options.
AB  - Although solitary presentations of infantile myofibromatosis tend toward
      spontaneous regression, multicentric forms fare worse. Previous case reports have
      depicted observation, surgical resection, and systemic therapies as treatment
      options. This paper reports well-tolerated, successful outcomes in a series of
      patients with high-risk infantile myofibromatosis in need of life-sustaining
      interventions treated with a combination of vincristine and dactinomycin. The
      clinical presentation, pathology, and radiographic findings are described. 

PMID- 25389918
TI  - Experiences of Pediatric Patients With Sickle Cell Disease in Rural Emergency
      Departments.
AB  - BACKGROUND: The aims of this study were to describe guardian perceptions of the
      experiences of a sample of youth with sickle cell disease (SCD) in rural
      emergency departments (EDs) with a focus on overall patient satisfaction and
      characteristics of care. PROCEDURE: Guardians of 139 children with SCD (0 to 17
      y) seen at a rural pediatric SCD clinic completed a survey concerning their
      children's ED experiences in the past 6 months, including information about ED
      wait times, quality of communications and interactions with the ED health care
      providers, pain management, perceptions of speed of care, and overall
      satisfaction. RESULTS: About 41% of guardians reported that their child visited
      the ED in the past 6 months. Guardians reported moderate satisfaction with ED
      care. About 25% of those who visited the ED indicated that health care providers
      did not spend enough time with them and their children did not receive speedy
      care. Shorter ED wait times and higher ratings of speed of care predicted higher
      satisfaction. CONCLUSIONS: Families of youth with SCD are experiencing longer
      wait times in rural EDs which contribute to dissatisfaction with care. Efforts
      are needed to develop strategies to reduce ED wait times and improve speed of
      care which may improve outcomes following ED care.

PMID- 25389920
TI  - Long-term antibody persistence in children after vaccination with the pediatric
      formulation of an aluminum-free virosomal hepatitis A vaccine.
AB  - BACKGROUND: The pediatric dose of the virosomal hepatitis A vaccine Epaxal,
      Epaxal Junior, is safe and immunogenic in children from 1 to 17 years of age. The
      present study investigated the long-term immunogenicity of Epaxal Junior. The
      standard doses of Epaxal and aluminum-adsorbed hepatitis A vaccine (Havrix
      Junior) were used as comparators. METHODS: A total of 271 children who had
      completed a 0/6-month immunization schedule (priming and booster dose)
      participated in this follow-up study. Anti-hepatitis A virus (HAV) antibody
      levels were measured using a microparticle enzyme immunoassay (HAVAB 2.0
      Quantitative; Abbott Diagnostics, Wiesbaden, Germany) starting at 18 months
      following the second dose, and then yearly until 66 months (ie, 5.5 years) after
      the second dose. RESULTS: All subjects tested at Month 66 still had protective
      anti-HAV antibodies (>=10 mIU/mL). Antibody titers were generally lower in
      subjects 1-7 years old than in subjects 8-17 years old and higher in females 11
      17 years old than in males 11-17 years old. In addition, an age-dependent decay
      was observed, that is, antibody decreased more rapidly in younger than in older
      children. CONCLUSIONS: Vaccination of children with two doses of Epaxal Junior
      confers a real-time protection of at least 5.5 years. This protection is
      estimated to last approximately 25 years. Younger children showed lower antibody
      titers and a faster antibody decline than older children. Additional follow-up
      studies are needed beyond 5.5 years to further assess the long-term
      immunogenicity of Epaxal Junior.

PMID- 25389921
TI  - Leprosy and disability in children younger than 15 years in an endemic area of
      northeast Brazil.
AB  - BACKGROUND: Leprosy in children is still a frequent but sometimes unrecognized
      public health problem and an important cause of disability. Establishing the risk
      factors that lead to the development of disability is important for the
      development of suitable prevention programs. We describe the incidence of leprosy
      and the prevalence and degree of associated disabilities in children<15 years of
      age at the time of first presentation to the health services in Aracaju, Sergipe,
      Northeast Brazil. METHODS: A retrospective case series of 266 cases of leprosy in
      children under 15 years old of Aracaju from 2001 to 2012. Logistic regressions
      were performed to identify factors for disability. RESULTS: The average detection
      rate was 16.5/100,000 children under 15 years old per year over the study period.
      Physical disability was associated with the presence of affected nerves and
      multibacillary leprosy. CONCLUSIONS: The detection rate of leprosy in children is
      still high in Aracaju, Northeast Brazil. Having affected nerves and
      multibacillary leprosy are associated with the development of disability in
      children.

PMID- 25389919
TI  - Etiology of bacteremia in young infants in six countries.
AB  - BACKGROUND: Neonatal illness is a leading cause of death worldwide; sepsis is one
      of the main contributors. The etiologies of community-acquired neonatal
      bacteremia in developing countries have not been well characterized. METHODS:
      Infants <2 months of age brought with illness to selected health facilities in
      Bangladesh, Bolivia, Ghana, India, Pakistan and South Africa were evaluated, and
      blood cultures taken if they were considered ill enough to be admitted to
      hospital. Organisms were isolated using standard culture techniques. RESULTS:
      Eight thousand eight hundred and eighty-nine infants were recruited, including
      3177 0-6 days of age and 5712 7-59 days of age; 10.7% (947/8889) had a blood
      culture performed. Of those requiring hospital management, 782 (54%) had blood
      cultures performed. Probable or definite pathogens were identified in 10.6%
      including 10.4% of newborns 0-6 days of age (44/424) and 10.9% of infants 7-59
      days of age (39/358). Staphylococcus aureus was the most commonly isolated
      species (36/83, 43.4%) followed by various species of Gram-negative bacilli
      (39/83, 46.9%; Acinetobacter spp., Escherichia coli and Klebsiella spp. were the
      most common organisms). Resistance to second and third generation cephalosporins
      was present in more than half of isolates and 44% of the Gram-negative isolates
      were gentamicin-resistant. Mortality rates were similar in hospitalized infants
      with positive (5/71, 7.0%) and negative blood cultures (42/557, 7.5%).
      CONCLUSIONS: This large study of young infants aged 0-59 days demonstrated a
      broad array of Gram-positive and Gram-negative pathogens responsible for
      community-acquired bacteremia and substantial levels of antimicrobial resistance.
      The role of S. aureus as a pathogen is unclear and merits further investigation.

PMID- 25389922
TI  - Bioinformatics: the next frontier of metabolomics.

PMID- 25389923
TI  - Effects of total-body digital photography on cancer worry in patients with
      atypical mole syndrome.
AB  - IMPORTANCE: Cancer worry about developing melanoma in at-risk patients may affect
      one's quality of life and adherence to screening. Little is known about melanoma
      related worry in patients with atypical mole syndrome (AMS). OBJECTIVES: To
      quantify levels and elucidate predictors of worry related to developing melanoma
      in patients with AMS and to determine whether total-body digital photography
      (TBDP) in pigmented lesion clinics (PLCs) reduces worry. DESIGN, SETTING, AND
      PARTICIPANTS: In this pretest-posttest study, patients with AMS from PLCs at 2
      academic medical centers were recruited from June 1, 2005, through October 31,
      2008, to answer questions about cancer worry before and after undergoing TBDP.
      Questionnaires used included the new melanoma and recurrent melanoma Revised
      Impact of Event Scale (RIES), the Melanoma Worry Scale (MWS), the Hospital
      Anxiety and Depression Scale, and the Life Orientation Test. INTERVENTIONS: All
      patients underwent TBDP. MAIN OUTCOMES AND MEASURES: Changes in the MWS and new
      melanoma RIES scores. RESULTS: A total of 138 patients completed baseline
      questionnaires; 108 patients (78.3%) completed questionnaires after TBDP.
      Baseline levels of worry were low and reduced further after TBDP. In patients
      with a personal history of melanoma, worry was reduced on all scales. In patients
      without a personal history of melanoma, only the new melanoma RIES score was
      significantly decreased. Predictors of baseline MWS scores include female sex,
      personal history of melanoma, and higher Hospital Anxiety and Depression Scale
      scores, adjusted for demographics, family history of melanoma, and Life
      Orientation Test scores. Adjusted predictors of the baseline new melanoma RIES
      score were similar but also included lower educational level and did not include
      sex. CONCLUSIONS AND RELEVANCE: Patients with AMS have low levels of melanoma
      related worry, which is similar to data from other populations at high risk of
      cancers. We found that TBDP is a clinically useful tool that can be used in PLCs
      to help decrease worry about developing melanoma in at-risk patients.

PMID- 25389924
TI  - Tumor-associated macrophages are a useful biomarker to predict recurrence after
      surgical resection of nonfunctional pancreatic neuroendocrine tumors.
AB  - OBJECTIVE: Patients with nonfunctional pancreatic neuroendocrine tumors (NF
      PNETs) have poorer survival than those with functional PNETs. Our objective was
      to identify risk factors for recurrence after resection to better define
      surveillance parameters to improve long-term outcomes. METHODS: A retrospective
      analysis was performed for NF-PNET patients who underwent resection at the
      University of Michigan from 1995 to 2012. Immunohistochemical staining of tissues
      from patients with and without disease recurrence was performed for Ki-67 and the
      macrophage marker CD68, as tumor-associated macrophages are important for PNET
      development and progression. Clinicopathological factors and patient outcomes
      were measured. RESULTS: Ninety-seven NF-PNET patients underwent surgical
      resection. There was a recurrence rate of 14.4% (14/97). The median time to
      recurrence was 0.61 years, with 10 (71%) patients recurring within the first 2
      years. Six of 7 patients (86%) monitored at 6-month surveillance intervals were
      diagnosed with recurrence on their first computed tomographic scan or during the
      intervening intervals. By Cox proportional hazards analysis, the most significant
      independent risk factors for recurrence were higher grade, stage, and
      intraoperative blood loss. High CD68 score and Ki-67 index correlated with
      recurrence risk, and Ki-67 index inversely correlated with time to recurrence. In
      patients who otherwise had few risk factors, a high CD68 score was a significant
      prognostic factor for recurrence. CONCLUSIONS: In patients with NF-PNETs, risk
      factors associated with recurrence were high EBL, grade, stage, CD68 score, and
      Ki-67 index. The CD68 score was an important prognostic factor in patients who
      otherwise had few clinicopathological risk factors; therefore, the CD68 score
      should be considered when planning surveillance strategies. We recommend that NF
      PNET patients at high risk of recurrence undergo initial surveillance every 3
      months for 2 years after surgery.

PMID- 25389926
TI  - Weighing the evidence: evaluating contributions from case reports and case
      series.

PMID- 25389925
TI  - Loss of keratinocyte focal adhesion kinase stimulates dermal proteolysis through
      upregulation of MMP9 in wound healing.
AB  - OBJECTIVE: To investigate how epithelial mechanotransduction pathways impact
      wound repair. BACKGROUND: Mechanical forces are increasingly recognized to
      influence tissue repair, but their role in chronic wound pathophysiology remains
      unknown. Studies have shown that chronic wounds exhibit high levels of matrix
      metalloproteinase 9 (MMP9), a key proteolytic enzyme that regulates wound
      remodeling. We hypothesized that epithelial mechanosensory pathways regulated by
      keratinocyte-specific focal adhesion kinase (FAK) control dermal remodeling via
      MMP9. METHODS: A standard wound model was applied to keratinocyte-specific FAK
      knockout (KO) and control mice. Rates of wound healing were measured and tissue
      was obtained for histologic and molecular analyses. Transcriptional and
      immunoblot assays were used to assess the activation of FAK, intracellular
      kinases, and MMP9 in vitro. A cell suspension model was designed to validate the
      importance of FAK mechanosensing, p38, and MMP9 secretion in human cells.
      Biomechanical testing was utilized to evaluate matrix tensile properties in FAK
      KO and control wounds. RESULTS: Wound healing in FAK KO mice was significantly
      delayed compared with controls (closure at 15 days compared with 20 days, P =
      0.0003). FAK KO wounds demonstrated decreased dermal thickness and collagen
      density. FAK KO keratinocytes exhibited overactive p38 and MMP9 signaling in
      vitro, findings recapitulated in human keratinocytes via the deactivation of FAK
      in the cell suspension model. Functionally, FAK KO wounds were significantly
      weaker and more brittle than control wounds, results consistent with the
      histologic and molecular analyses. CONCLUSIONS: Keratinocyte FAK is highly
      responsive to mechanical cues and may play a critical role in matrix remodeling
      via regulation of p38 and MMP9. These findings suggest that aberrant epithelial
      mechanosensory pathways may contribute to pathologic dermal proteolysis and wound
      chronicity.

PMID- 25389927
TI  - An atypical white dot syndrome after traumatic subretinal hemorrhage.
AB  - PURPOSE: The purpose of this report was to describe a case of an atypical white
      dot syndrome that developed 10 weeks after a traumatic subretinal hemorrhage.
      METHODS: Retrospective chart review. RESULTS: A 24-year-old woman presented 2
      days after being punched in her right eye. A subretinal hemorrhage was present
      along the inferotemporal vascular arcades of the affected eye. The hemorrhage was
      slowly resolving until 10 weeks later when the patient noticed a new superonasal
      scotoma and floaters in her right eye. Deep retinal and retinal pigment
      epithelial gray-white spots were present inferotemporally around the hemorrhage.
      These spots were identifiable on fundus autofluorescence photography, fluorescein
      angiography, and indocyanine green angiography. A subretinal inflammatory mass
      was identified adjacent to the subretinal hemorrhage. In addition, there was mild
      vitritis, acute papillitis, retinal vasculitis, and photoreceptor disruption
      visible on spectral domain optical coherence tomography. The patient was started
      on oral prednisone with subsequent improvement in signs and symptoms. CONCLUSION:
      Ocular trauma with subretinal hemorrhage may induce a white dot syndrome sharing
      some features with Multiple Evanescent White Dot Syndrome and Multiocal
      Choroiditis and Panuveitis.

PMID- 25389928
TI  - Primary branch retinal artery occlusion in idiopathic retinal vasculitis,
      aneurysms, and neuroretinitis syndrome associated with hyperhomocysteinemia.
AB  - PURPOSE: The purpose of this study was to report primary branch retinal artery
      occlusion in a case with idiopathic retinal vasculitis, aneurysms, and
      neuroretinitis syndrome. METHODS: Review of medical case records, color fundus
      photographs, and fundus fluorescein angiography of a 23-year-old man diagnosed
      with idiopathic retinal vasculitis, aneurysms, and neuroretinitis. PATIENT: A 23
      year-old man presented with sudden painless decreased vision in right eye since 1
      day. Ocular examination revealed a best-corrected visual acuity of counting
      fingers 1 feet in the right eye and 20/20 in the left eye, relative afferent
      pupillary defect in the right eye, 1+ vitreous cells in both eyes, optic disk
      neovascularization with massive peripapillary and perivascular lipid exudation,
      and occluded smaller vessels in both eyes. In addition, there was an area of
      retinal opacification in the posterior pole along the inferotemporal arcade in
      the right eye. The patient underwent color fundus photography, fluorescein
      angiography, and a detailed systemic workup. RESULTS: Fundus fluorescein
      angiographic features were suggestive of idiopathic retinal vasculitis,
      aneurysms, and neuroretinitis in both eyes with branch retinal artery occlusion
      in the right eye. Detailed systemic workup revealed raised serum homocysteine
      levels. The patient underwent scatter retinal photocoagulation in both eyes and
      also was started on folic acid and pyridoxine supplementation. At 1 year of
      follow-up, the best-corrected visual acuity in the right eye improved to 20/60.
      Posterior segment examination showed reduced exudation, resolution of optic disk
      neovascularization in both eyes, and clearing of retinal opacification in the
      right eye. Also, the levels of serum homocysteine decreased over 1 year.
      CONCLUSION: Primary branch retinal artery occlusion can be an atypical
      presentation of idiopathic retinal vasculitis, aneurysms, and neuroretinitis
      syndrome. Such a case should be thoroughly investigated for underlying
      hypercoagulable state. Also, a careful long-term follow-up is required for these
      patients to prevent any neovascularization sequelae.

PMID- 25389929
TI  - Epimacular brachytherapy for the treatment of retinal angiomatous proliferation.
AB  - PURPOSE: The purpose of this study was to present a case of a retinal angiomatous
      proliferation (RAP) treated with epimacular brachytherapy that was refractory to
      continued ranibizumab therapy. PATIENTS: An interventional case report of an 89
      year-old woman with angiographically confirmed RAP had shown a poor response to 8
      anti-vascular endothelial growth factor (anti-vascular endothelial growth factor)
      retreatment injections over a 10-month period. METHODS: The patient underwent
      pars plana vitrectomy combined with beta irradiation of the RAP lesion using a
      Strontium-90 applicator (NeoVista). The device was positioned over the lesion to
      deliver 24 gray over 4.5 minutes. Early Treatment Diabetic Retinopathy Study best
      corrected visual acuity with full refraction was undertaken monthly by trial
      certified examiners, independent of the operating surgeon. The main outcome
      measures were Early Treatment Diabetic Retinopathy Study best-corrected visual
      acuity, central retinal thickness measured by optical coherence tomography, and
      the number of anti-vascular endothelial growth factor retreatments. RESULTS:
      Preoperative best-corrected visual acuity was 53 letters (20/80), improving to 69
      letters (20/50) at 12 months and 71 letters (20/40) at 21 months. Only one
      ranibizumab retreatment was required, at Month 2. Optical coherence tomography
      central retinal thickness reduced from 312 MUm to 224 MUm with a return of the
      normal foveal contour. There was full regression of the RAP lesion on clinical
      examination, with a reduction in lesion activity demonstrated by fundus
      fluorescein angiography. CONCLUSION: This is the first reported case of RAP
      treated with epimacular brachytherapy, with encouraging results. Epimacular
      brachytherapy may be a new treatment option for refractory RAP lesions requiring
      frequent intravitreal ranibizumab, but further studies are needed.

PMID- 25389930
TI  - Birdshot-like chorioretinopathy in common variable immunodeficiency.
AB  - PURPOSE: To describe a patient with ocular manifestations secondary to common
      variable immunodeficiency. METHODS: A 17-year-old adolescent girl presented with
      asymptomatic bilateral optic disk edema and chorioretinal infiltrates. These
      findings were noted during routine follow-up visits for hydroxychloroquine use
      for lymphoid interstitial pneumonia. She underwent a full ophthalmologic and
      systemic work-up. RESULTS: At the age of 13, the patient was diagnosed with
      common variable immunodeficiency with splenomegaly, lymphadenopathy, and lymphoid
      interstitial pneumonia. Progressive generalized lymphadenopathy developed
      thereafter. Since the diagnosis of common variable immunodeficiency, she received
      monthly intravenous immunoglobulin, systemic corticosteroids and later on, oral
      hydroxychloroquine. Annual routine screening visits to exclude retinal
      hydroxychloroquine toxicity were unremarkable until age 17. Unaided visual acuity
      was 6/5 in both eyes. Slit-lamp examination was normal, whereas fundoscopy
      revealed bilateral optic disk edema and birdshot-like chorioretinal infiltrates,
      without signs of vitritis. A bilateral hot disk was seen on fluorescein
      angiography, but there were no signs of vasculitis. Indocyanine green angiography
      showed macular and midperipheral choroidal granulomas. A brain magnetic resonance
      imaging scan revealed no signs of raised intracranial pressure. Human leukocyte
      antigen-typing was negative for HLA-A29, making birdshot chorioretinopathy highly
      unlikely. The results of a work-up for sarcoidosis were not typical of that
      disease. During the past months, a remarkable episode of lacrimal gland swelling
      with spontaneous recovery was noted. CONCLUSION: We describe a case of ocular
      manifestations of common variable immunodeficiency, including asymptomatic
      bilateral chorioretinal granulomas mimicking birdshot chorioretinopathy, combined
      with optic nerve sheath infiltration, and lacrimal gland involvement.

PMID- 25389931
TI  - Unilateral birdshot-like choroidopathy: a case report.
AB  - PURPOSE: To report on an unusual case of unilateral birdshot-like choroidopathy
      and to describe its clinical characteristics. METHODS: Prospective follow-up
      study of clinical, laboratory, electrophysiologic, and angiographic evolution of
      a patient with choroidal lesions mimicking birdshot chorioretinitis. MAIN
      OUTCOMES MEASURES: Visual acuity, serial visual fields, spectral domain optical
      coherent tomography, electrophysiologic studies: full-field electroretinogram,
      pattern electroretinogram, multifocal electroretinogram, and electrooculogram.
      Fluorescein angiography, indocyanine green angiography, color vision and contrast
      sensitivity studies. PATIENTS/DESIGN: Observational case report. RESULTS: At 30
      months of follow-up, visual acuity was 20/20 in both eyes. There were no signs of
      intraocular inflammation at any time over follow-up. Serial visual field showed
      no abnormality. Electrophysiologic studies reflected normal retinal function.
      Color vision and contrast sensitivity were both normal. Fluorescein angiography
      depicted unilateral hypofluorescent choroidal spots in early phases becoming
      hyperfluorescent in late frames without changes over follow-up. Indocyanine green
      angiography pointed out diffuse hypofluorescent choroidal lesions in early and
      late frames that did not modify over follow-up. CONCLUSIONS: We present an
      interesting but unusual case of idiopathic unilateral choroidal lesions mimicking
      those seen in birdshot chorioretinitis but without evidence of active
      inflammation. Our case has been called unilateral birdshot-like choroidopathy on
      the basis of the characteristics of the lesions and the lack of active
      inflammation. The patient has been followed up for 30 months without treatment,
      and no changes in visual function or clinical features have been observed.
      Clinicians should be aware of the diagnostic criteria of birdshot chorioretinitis
      to avoid unnecessary treatment of patients with other diseases mimicking
      birdshot.

PMID- 25389932
TI  - Late-onset cystoid macular edema as a presenting symptom of anca-negative
      pauciimmune crescentic glomerulonephritis.
AB  - PURPOSE: The purpose of this study was to report the appearance of late-onset
      cystoid macular edema (CME) as an initial manifestation of antineutrophil
      cytoplasmic antibody-negative pauciimmune glomerulonephritis. METHODS: Optical
      coherence tomography was obtained on a female patient after presentation of CME
      after cataract surgery in the right eye. Follow-up optical coherence tomographies
      were obtained after resolution of symptoms and on development and resolution of
      CME in the fellow eye. RESULTS: The patient developed unilateral CME 6 months
      after uncomplicated cataract surgery and after a seizure was diagnosed with
      antineutrophil cytoplasmic antibody-negative pauciimmune glomerulonephritis. The
      CME resolved within 2 months of initiating topical nonsteroidal antiinflammatory
      drug and steroid treatment. Several months later, after undergoing uncomplicated
      cataract surgery in the fellow eye, the patient developed CME 4 weeks after
      surgery despite topical nonsteroidal antiinflammatory drug and steroid
      prophylaxis. The CME quickly resolved with topical treatment, and there has been
      no recurrent CME in either eye. Review of the literature shows a potential shared
      mechanism of CME and antineutrophil cytoplasmic antibody-negative pauciimmune
      glomerulonephritis. CONCLUSION: These findings demonstrate a potential
      association between CME and antineutrophil cytoplasmic antibody-negative
      pauciimmune glomerulonephritis. Patients with this form of glomerulonephritis may
      benefit from pre- and postoperative topical antiinflammatory prophylaxis.

PMID- 25389933
TI  - Vision loss 2 weeks after uneventful optic nerve sheath fenestration surgery may
      be attributed to retinal reperfusion injury.
AB  - PURPOSE: The purpose of this study was to report a rare case of retinal
      reperfusion injury after optic nerve sheath fenestration surgery. PATIENTS AND
      METHODS: Single patient case report. RESULTS: A 58-year-old African American
      woman presented with severe visual loss in the right eye 2 weeks after optic
      nerve sheath fenestration surgery. Retinal examination at presentation showed
      severe arterial narrowing and the appearance of new intraretinal hemorrhages.
      Fluorescein angiography demonstrated delayed venous filling. CONCLUSION: Severe
      visual loss after optic nerve sheath fenestration procedure is uncommon. This
      case may represent the first reported case of reperfusion injury in human eyes.

PMID- 25389934
TI  - Magnetic resonance imaging-determined subretinal fluid volume in an uveitic
      patient.
AB  - PURPOSE: To describe the usefulness of the magnetic resonance imaging-determined
      subretinal fluid volume to evaluate the therapeutic effect on the retinal
      detachment caused by uveitis with the clouded media. METHODS: We obtained the
      images by half-Fourier single-shot rapid acquisition with relaxation enhancement
      magnetic resonance imaging using a microscopy coil. We measured the area of
      subretinal fluid on each image and calculated the volume of subretinal fluid by
      multiplying the total area by the slice thickness. RESULTS: A 56-year-old male
      who had lost his central visual field developed bullous retinal detachment in
      both eyes associated with uveitis. We treated him with steroid pulse therapy. We
      could not accurately evaluate the improvement of retinal detachment by
      ophthalmoscopy and ultrasonography as a result of the clouded media. We measured
      the volume of the subretinal fluid using magnetic resonance imagings. The volume
      of the subretinal fluid was observed to gradually decrease. These methods enable
      us to obtain clear magnetic resonance images within 2 seconds per slice. The
      reproducibility of the volumetry obtained by magnetic resonance imaging was
      excellent. CONCLUSION: The adaptation of half-Fourier single-shot relaxation
      enhancement imaging performed with a surface coil makes it possible to evaluate
      the volumetry of a targeted space while also being useful for evaluating the
      effect of the treatment.

PMID- 25389935
TI  - Widespread vitreoretinal traction simulating retinal vasculitis in a patient with
      uveitis.
AB  - PURPOSE: To describe a case of uveitis with widespread vitreoretinal traction
      simulating retinal vasculitis angiographically. METHODS: Interventional case
      report. RESULTS: A 62-year-old woman was examined for low vision in her left eye
      that persisted for ~1 year. She had been treated for polymyalgia rheumatica for 1
      year. Visual acuity was 20/20 in the right eye and 20/100 in the left eye. There
      were a few aged vitreous cells in both eyes. On fundus examination, there was
      mild epiretinal membrane in the left eye. Fluorescein angiography revealed
      diffuse fluorescein leakage in the late phase of angiography in the macular
      peripapillary and superior retinal hemisphere in the left eye, which appeared
      similar to retinal vasculitis. With optical coherence tomography, there was
      vitreomacular traction on the macular, peripapillary, and major branches of
      vessels in the left eye. Fundus examination was normal in the right eye. Pars
      plana vitrectomy was performed in the left eye uneventfully. Visual acuity was
      40/100 at the postoperative 1-year follow-up. CONCLUSION: Vitreoretinal traction
      can be widespread and can cause diffuse fluorescein leakage resembling vasculitis
      or other types of uveitis.

PMID- 25389936
TI  - Continued vision loss from progressive expansion of inactive chorioretinal scars
      in a myopic patient with well-controlled sympathetic ophthalmia.
AB  - PURPOSE: To describe significant vision loss caused by enlargement of
      chorioretinal scars related to sympathetic ophthalmia despite adequate control of
      intraocular inflammation. METHODS: A case report of a 62-year-old man who
      developed sympathetic ophthalmia after a vitrectomy, which was successful in
      repairing a rhegmatogenous retinal detachment. RESULTS: Progressive expansion of
      chorioretinal scars occurred despite successful control of intraocular
      inflammation related to sympathetic ophthalmia. The visual acuity declined from
      20/20 to no light perception in the right eye and from 20/400 to light perception
      in the left eye over 11 years of follow-up. CONCLUSION: Progressive enlargement
      of chorioretinal scars and visual loss may occur despite adequate control of
      intraocular inflammation in patients with sympathetic ophthalmia. Similar
      patterns of scar expansion have been reported in eyes after laser
      photocoagulation, but we believe this is the first report of scar enlargement in
      the setting of well-controlled sympathetic ophthalmia.

PMID- 25389937
TI  - Intraretinal silicone oil after retinal detachment repair.
AB  - PURPOSE: To report a case of intraretinal silicone oil incorporation after
      anatomically successful detachment surgery. METHODS: Retrospective case report.
      RESULTS: We show a sequence of optical coherence tomography images documenting
      silicone oil incorporation from the vitreous cavity over a 3-months period. This
      resulted in foveal cystic spaces filled with a hyperreflective material and best
      corrected visual acuity of 30/200. CONCLUSION: Intraretinal incorporation of
      silicone oil is rare and mainly occurs via subretinal access in cases with
      chronically detached retina. However, other mechanisms are possible. Here, we
      document a case of intraretinal silicone oil incorporation from the vitreous
      cavity after anatomically successful detachment surgery.

PMID- 25389938
TI  - Delayed suprachoroidal hemorrhage after cataract surgery.
AB  - PURPOSE: To describe the clinical course of 61-year-old man who developed a
      delayed suprachoroidal hemorrhage 4 days after cataract surgery. METHOD: This is
      an observational case report. The patient's clinical course is reviewed, and his
      clinical findings are correlated to B-scan ultrasonography and posterior
      funduscopic photography. We describe a successful surgical intervention with
      external sclerotomy and partial drainage of the suprachoroidal hemorrhage.
      RESULTS: Initial medical management of delayed suprachoroidal hemorrhage failed
      to improve the patient's pain, vision, and clinical findings. Two weeks later, an
      external sclerotomy with partial drainage of the suprachoroidal blood resulted in
      an expedited pain relief, with complete resolution of the suprachoroidal
      hemorrhage and restoration of baseline visual acuity. CONCLUSION: Delayed
      suprachoroidal hemorrhage is a well-recognized but rare postoperative
      complication of cataract surgery. This case highlights the benefits of a timely
      surgical intervention after conservative management. We propose that a
      conservative external surgical approach with partial drainage of a suprachoroidal
      hemorrhage and closure by secondary intention was sufficient to tip the balance
      of intraocular hemodynamics and led to full recuperation.

PMID- 25389939
TI  - Central serous chorioretinopathy associated with the use of spironolactone,
      aldosterone receptor antagonist.
AB  - PURPOSE: To report a case of central serous chorioretinopathy caused by the use
      of spironolactone, a competitive antagonist of aldosterone. METHODS: Case report
      and review of the literature. RESULTS: A 26-year-old white woman on Aldactone
      (spironolactone) for the treatment of acne and Adderall
      (dextroamphetamine/amphetamine) for the treatment of attention deficit
      hyperactivity disorder, developed central serous chorioretinopathy, which
      resolved upon discontinuation of spironolactone and remitted after restarting it.
      CONCLUSION: It is likely that spironolactone use contributed to the development
      of central serous chorioretinopathy in this patient. Concomitant use of
      amphetamine may also have played a role.

PMID- 25389940
TI  - Active silicone oil removal with a modified vacuum syringe.
AB  - PURPOSE: At present, the number of clinical indications for the use of silicone
      oil (SO) has increased in intraocular surgery because of the advent of new
      techniques in vitreoretinal surgery, availability of better quality oils, and
      greater experience in its use. Consequently, the number of procedures for SO
      removal has increased, and support technologies for these procedures are always a
      concern. METHODS: A simple active technique for SO removal based on a 5-mL
      standard syringe with an 18G cannula was developed. The oil is suctioned into the
      syringe by the pulling effect of a spring assembled along the axis of the piston.
      No abrupt change in the intraocular pressure is produced because of the oil
      viscosity and the reduced diameter of the cannula. RESULTS: A technique for SO
      removal that has been used successfully during the past 7 years is presented in
      this article. During the 7-year period, 234 SO removals were performed without
      any complication or device failure. Using the present method, the average time
      for SO removal was 4 minutes. CONCLUSION: The average extraction time with the
      technique is 4 minutes, which is in the range of other active techniques, and it
      is faster than passive methods that are performed between 8 and 9 minutes. The
      technique is in line with the advantages of more elaborated active methods
      without using complex technology. It is considered to be highly successful and
      easy to implement.

PMID- 25389941
TI  - Subretinal tenecteplase injection in a submacular hemorrhage from polypoidal
      choroidal vasculopathy: a case report.
AB  - PURPOSE: The purpose of this report was to describe a case with a thick
      submacular hemorrhage (SMH) resulting from polypoidal choroidal vasculopathy that
      was successfully treated with a subretinal tenecteplase injection. METHODS: A
      retrospective case report. RESULTS: A 63-year-old man with acute SMH secondary to
      polypoidal choroidal vasculopathy underwent a partial posterior vitrectomy, a
      subretinal tenecteplase (100 MUg/0.1 mL) injection with air/fluid exchange, and
      an intravitreal injection of bevacizumab (2.5 mg/0.1 mL). His preoperative
      corrected visual acuity was 20/30, but the SMH threatened the fovea. The SMH was
      displaced inferiorly and absorbed completely at 1 month postoperative. His visual
      acuity decreased to 20/40 1 week postoperative but recovered to 20/20 2 months
      after surgery. The electroretinogram showed no distinct elongation of implicit
      time and slightly decreased amplitude of a-wave and b-wave at 3 months
      postoperative; optical coherence tomography presented disruption of the inner
      segment/outer segment line at the onset of SMH but recovered completely at 3
      months postoperative. CONCLUSION: Subretinal tenecteplase was found to have
      sufficient hemolytic function and no retinal toxicity and could represent a
      feasible treatment option for the management of SMH.

PMID- 25389942
TI  - Regression of advanced group e retinoblastoma with intraarterial chemotherapy.
AB  - PURPOSE: To report a case of regression of advanced retinoblastoma with
      intraarterial chemotherapy. METHODS: A 25-month-old boy presented with extensive
      endophytic group E retinoblastoma with extensive vitreous seeds and total retinal
      detachment. RESULTS: The patient underwent four sessions of intraarterial
      chemotherapy after which there was complete regression of vitreous seeds and near
      complete calcification of the tumor. CONCLUSION: Intraarterial chemotherapy is a
      novel treatment that is effective in selected cases of retinoblastoma. This
      technique allows selective delivery of chemotherapy to the involved tumor tissue
      with minimal systemic absorption.

PMID- 25389943
TI  - Choroidal neovascularization after intraocular foreign body injury.
AB  - PURPOSE: To report the use of bevacizumab to treat intraocular foreign body
      induced choroidal neovascularization. METHODS: An intraocular foreign body was
      diagnosed clinically and confirmed via optical coherence tomography and head
      computed tomography. Fluorescein angiography was used to confirm the diagnosis of
      choroidal neovascular membrane on follow-up examination. The patient was treated
      with vitrectomy and intravitreal bevacizumab with follow-up at progressive
      intervals to determine the treatment response. RESULTS: The visual acuity was
      measured at 20/20 1 year after vitrectomy, with no recurrence of choroidal
      neovascularization. CONCLUSION: Intravitreal bevacizumab should be considered a
      useful alternative or adjunct to photocoagulation for the treatment of choroidal
      neovascularization due to intraocular foreign body.

PMID- 25389944
TI  - Macular hole associated with sarcoidosis.
AB  - PURPOSE: To describe an interventional case report of macular hole associated
      with sarcoidosis. METHODS: A 63-year-old African American woman presented with
      unilateral decreased vision in the right eye. Clinical examination, ultra wide
      field fluorescein angiography, and optical coherence tomography revealed a
      macular hole in the setting of intraocular inflammation. Pars plana vitrectomy
      was performed to close the macular hole, and a vitreous biopsy was performed.
      RESULTS: The patient had closure of the macular hole and tissue confirmation of
      ocular sarcoidosis by vitreous biopsy. CONCLUSION: Macular hole associated with
      sarcoidosis is exceedingly rare. Surgical intervention may be necessary to close
      the macular hole and improve vision.

PMID- 25389945
TI  - Profound postoperative hypotony with globe collapse after 25-gauge pars plana
      vitrectomy.
AB  - PURPOSE: To report a series of cases of profound hypotony with globe collapse on
      postoperative day 1 after sutureless 25-gauge pars plana vitrectomy and to
      identify common risk factors for this complication. METHODS: Retrospective chart
      review of three patients. Ocular history and surgeries, preoperative diagnosis,
      operative technique, postoperative and final visual acuities, reformation
      intervention, and need for additional surgery were reviewed. RESULTS: Three cases
      were reviewed. Patient ages were 22, 53, and 53 years. All patients had a history
      of a rhegmatogenous retinal detachment repaired by surgery and all had at least
      one vitrectomy. Two had a prior scleral buckle and two had pathologic myopia. All
      patients underwent sutureless 25-gauge pars plana vitrectomy. No patient had
      intraocular air, gas, or silicone oil tamponade. All patients presented on
      postoperative day 1 with globe collapse, hand motion vision, and scleral
      infolding. All patients underwent office-based injection of sterile balanced salt
      solution or air. One patient required an additional procedure-operative closure
      of sclerotomies and intraocular gas tamponade. All three patients attained a
      final Snellen visual acuity of 20/50 or 20/60. CONCLUSION: These cases represent
      a small fraction (0.12%) of patients who underwent 25-gauge pars plana vitrectomy
      by one surgeon. Patients had several risk factors, including severe eye disease,
      prior retinal detachment repair, prior vitrectomy, pathologic myopia, and lack of
      intraocular tamponade. In patients with several risk factors, consideration
      should be given for intraocular gas or air injection or sclerotomy closure.

PMID- 25389946
TI  - Role of famciclovir in the management of acute retinal necrosis in developing
      countries.
AB  - PURPOSE: To evaluate clinical presentations, management strategies, and results
      in patients with acute retinal necrosis (ARN) who received famciclovir. METHODS:
      In a retrospective, noncomparative, interventional case series, we reviewed case
      records of patients with ARN from the computerized database between January 2007
      and December 2009. Data collected included demographic details of the patient,
      relevant history, examination findings, drugs administered, clinical response,
      and final visual acuity. The main outcome measures were visual acuity and
      clinical response. RESULTS: Famciclovir was administered in three cases of ARN.
      In these three immunocompetent patients, there was complete resolution of ARN
      with improvement in visual acuity and absence of other eye involvement or
      recurrence in the primary eye. CONCLUSION: One may consider treating ARN with
      oral famciclovir in immunocompetent patients in developing countries when
      intravenous acyclovir treatment is not affordable to the patient or when there is
      clinical resistance to acyclovir.

PMID- 25389947
TI  - Bilateral drug (ipilimumab)-induced vitritis, choroiditis, and serous retinal
      detachments suggestive of vogt-koyanagi-harada syndrome.
AB  - PURPOSE: To report a case of bilateral drug (ipilimumab)-induced vitritis,
      choroiditis, and serous retinal detachments suggestive of Vogt-Koyanagi-Harada
      syndrome. METHODS: This is a single case report. RESULTS: A 43-year-old woman
      with metastatic melanoma reported a 1-day history of blurry vision after starting
      a phase 1 clinical trial of ipilimumab, a cytotoxic T lymphocyte-associated
      antigen 4 blocker, 2 weeks before presentation. Fundus examination of both eyes
      showed bilateral serous detachments with associated vitritis and choroiditis.
      Optical coherence tomography confirmed the presence of serous detachments, and
      fluorescein angiography demonstrated multiple areas of pinpoint leakage at the
      level of the retinal pigment epithelium. Treatment with high-dose corticosteroids
      led to a rapid improvement in vision and resolution of her serous detachments.
      Ten weeks after initial presentation, the patient developed vitiligo and
      poliosis. CONCLUSION: Vogt-Koyanagi-Harada syndrome is a bilateral granulomatous
      panuveitis associated with dermatologic, neurologic, and audiologic
      manifestations of yet an unclear pathogenesis. To our knowledge, we report the
      first case of ipilimumab treatment resulting in the acute presentation of
      bilateral vitritis, choroiditis, and serous detachments suggestive of Vogt
      Koyanagi-Harada syndrome, which has particular significance because it may
      corroborate previous research attempting to elucidate the underlying mechanism of
      the disease.

PMID- 25389948
TI  - Scleral erosion, phthisis bulbi, and orbital pseudocyst formation as a late
      complication of miragel scleral buckle surgery.
AB  - PURPOSE: The purpose of this study was to report a case of scleral erosion as a
      late complication of Miragel scleral buckle surgery. The resulting defect in the
      eye wall was associated with a phthisical eye and an inferior orbital
      pseudocystic lesion. METHODS: Case report. RESULTS: An 81-year-old white woman
      presented with a Miragel scleral buckle 23 years after retinal detachment repair
      in the right eye. She complained of redness, swelling, and pain in the right eye,
      which was completely blind from glaucoma. There was evidence of implant extrusion
      in the inferior cul-de-sac. Orbital computed tomography scan revealed an inferior
      orbital cystic-appearing lesion. At the time of surgery, a fragmented Miragel
      implant was removed and 5 mL of clear fluid were drained from the pseudocyst. A
      2.5-cm defect in the eye wall was partially repaired. CONCLUSION: Scleral erosion
      as a late complication of scleral buckle surgery is relatively well described
      with the buckle becoming visible in the subretinal space on funduscopic
      evaluation. Progression to a full-thickness scleral defect is uncommon. We
      present a unique case of postbuckle scleral necrosis associated with involution
      of the globe and development of a contiguous orbital pseudocyst.

PMID- 25389949
TI  - Migrating behavior of presumed Toxocara presenting as punctate inner
      choroidopathy, idiopathic choroidal neovascularization, and diffuse unilateral
      subacute neuroretinitis.
AB  - PURPOSE: To document the intraretinal migration of presumed toxocara larvae
      mimicking punctate inner choroidopathy, idiopathic choroidal neovascularization,
      and diffuse unilateral subacute neuroretinitis. METHODS: Sequential color
      photographs, fluorescein angiograms, and optical coherence tomography were
      performed in three unrelated adult patients with presumed ocular toxocariasis.
      RESULTS: Characteristic fundoscopic manifestations simulating punctate inner
      choroidopathy, idiopathic choroidal neovascularization, and diffuse unilateral
      subacute neuroretinitis were reported in these patients, respectively.
      CONCLUSION: Presumed toxocara larvae must be included as a potential cause of
      different inflammatory diseases as a result of its migration through the retinal
      layers.

PMID- 25389950
TI  - Unique optical coherence tomography findings in a case of macular retinitis
      caused by subacute sclerosing panencephalitis.
AB  - BACKGROUND: Subacute sclerosing panencephalitis is a rare neurodegenerative
      disease. The ophthalmologic findings, typically necrotizing retinitis, often
      precede other neurologic signs and symptoms. Ocular findings are helpful for
      early diagnosis, but the findings of optical coherence tomography (OCT) images in
      an active phase of retinitis have never been reported. We report unique findings
      of OCT images in a case of subacute sclerosing panencephalitis. PATIENT AND
      METHODS: A 13-year-old boy was referred to our hospital complaining of visual
      loss and other neurologic symptoms. RESULTS: The fundus examination showed
      necrotizing retinitis. The OCT images showed empty spaces involving all layers of
      retina except the inner limiting membrane and hyperreflective lesion in inner
      retina. The diagnosis of subacute sclerosing panencephalitis was made from the
      blood and the spinal cerebral fluid test. DISCUSSION: This is the first report on
      OCT images of necrotizing retinitis in an active stage of subacute sclerosing
      panencephalitis case. The unique findings of OCT images as in this case help to
      diagnose the rare devastating disease.

PMID- 25389951
TI  - Effects of short term mild L-Thyroxine suppression therapy on myocardial
      functions, and its assessment with tissue Doppler imaging.
AB  - BACKGROUND: While adverse effects of overt hyperthyroidism on the cardiovascular
      system are well-known, the effects of subclinical hyperthyroidism are not clear.
      The aim of the study was to investigate the effects of short term mild L
      thyroxine (LT4) suppression therapy on myocardial functions in a group of
      premenopausal women with goiter, by using echocardiographic methods and tissue
      Doppler imaging (TDI). METHODS: Sixteen participants with goiter received LT4
      suppression therapy to keep TSH levels between 0.1-0.4 uIU/mL. After baseline and
      1st month assessment, 6-weeks follow-up were scheduled until 6th month assessment
      to adjust the medication dose during study period. All TSH levels decreased below
      0.4 MUIU/mL by the end of first month and stayed below this level throughout
      study period. At the beginning of the study and at month 6, the thyroid
      ultrasonography, Holter monitorization test, stress test, electrocardiograms and
      echocardiograms of participants were assessed. This was followed by a comparison
      of baseline and 6th month data. RESULTS: Baseline and 6th month 2-D
      echocardiography measurements of participants revealed that mean left ventricle
      diameter in diastole (4.1+/-0.3 vs 3.8+/-0.2 mm) and posterior wall thickness in
      diastole (0.9+/-0.1 vs. 0.8+/-0.1 mm) decreased (P<0.05); while stroke volume
      (41.9+/-9.9 vs. 48+/-8.2), stroke volume index (25.6+/-5.4 vs. 29.4+/-4.7),
      cardiac output (3.5+/-1.4 vs. 3.9+/-0.9) and cardiac index (2.2+/-0.8 vs. 2.4+/
      0.5) increased (P<0.05). Other 2D echocardiography parameters did not change
      significantly. The pulse wave Doppler examination, stress test and Holter
      monitorization of participants did not reveal any difference between baseline and
      6th month measurements. No statistically significant difference was observed in
      measurements of TDI except decreased septum S velocity. CONCLUSIONS: Short term
      mild LT4 suppression treatment did not cause systolic or diastolic dysfunction,
      or conduction defect in the heart; therefore may be safe in premenopausal females
      with not known cardiac disease.

PMID- 25389952
TI  - New design strategy for reversible plasticity shape memory polymers with
      deformable glassy aggregates.
AB  - Reversible plasticity shape memory (RPSM) is a new concept in the study of shape
      memory performance behavior and describes a phenomenon in which shape memory
      polymers (SMPs) can undergo a large plastic deformation at room temperature and
      subsequently recover their original shape upon heating. To date, RPSM behavior
      has been demonstrated in only a few polymers. In the present study, we implement
      a new design strategy, in which deformable glassy hindered phenol (AO-80)
      aggregates are incorporated into an amorphous network of epoxidized natural
      rubber (ENR) cured with zinc diacrylate (ZDA), in order to achieve RPSM
      properties. We propose that AO-80 continuously tunes the glass transition
      temperature (Tg) and improves the chain mobility of the SMP, providing traction
      and anchoring the ENR chains by intermolecular hydrogen bonding interactions. The
      RPSM behavior of the amorphous SMPs is characterized, and the results demonstrate
      good fixity at large deformations (up to 300%) and excellent recovery upon
      heating. Large energy storage capacities at Td in these RPSM materials are
      demonstrated compared with those achieved at elevated temperature in traditional
      SMPs. Interestingly, the further revealed self-healing properties of these
      materials are closely related to their RPSM behavior. 

PMID- 25389953
TI  - Rectification in tunneling junctions: 2,2'-bipyridyl-terminated n
      alkanethiolates.
AB  - Molecular rectification is a particularly attractive phenomenon to examine in
      studying structure-property relationships in charge transport across molecular
      junctions, since the tunneling currents across the same molecular junction are
      measured, with only a change in the sign of the bias, with the same electrodes,
      molecule(s), and contacts. This type of experiment minimizes the complexities
      arising from measurements of current densities at one polarity using replicate
      junctions. This paper describes a new organic molecular rectifier: a junction
      having the structure Ag(TS)/S(CH2)11-4-methyl-2,2'-bipyridyl//Ga2O3/EGaIn
      (Ag(TS): template-stripped silver substrate; EGaIn: eutectic gallium-indium
      alloy) which shows reproducible rectification with a mean r(+) = |J(+1.0 V)|/|J(
      1.0 V)| = 85 +/- 2. This system is important because rectification occurs at a
      polarity opposite to that of the analogous but much more extensively studied
      systems based on ferrocene. It establishes (again) that rectification is due to
      the SAM, and not to redox reactions involving the Ga2O3 film, and confirms that
      rectification is not related to the polarity in the junction. Comparisons among
      SAM-based junctions incorporating the Ga2O3/EGaIn top electrode and a variety of
      heterocyclic terminal groups indicate that the metal-free bipyridyl group, not
      other features of the junction, is responsible for the rectification. The paper
      also describes a structural and mechanistic hypothesis that suggests a partial
      rationalization of values of rectification available in the literature. 

PMID- 25389955
TI  - Influence of living situation on vulnerable elderly: focus on nutritional status.
AB  - OBJECTIVES: We compared the nutritional status of elderly people living in two
      different settings (shared-housing arrangements and home-living arrangements).
      DESIGN: For this secondary analysis, a cross-sectional study was performed.
      SETTING: For the home-living setting, home-dwelling elderly people from Hamburg,
      Germany who were participants in a prior study were included. For the shared
      housing arrangements (SHA) setting, we used baseline data from the WGQual Study.
      PARTICIPANTS: The sample from the home-living setting comprised patients who were
      discharged from a geriatric rehabilitation clinic within the six months prior to
      data collection. The sample from the shared-housing arrangements comprised all
      residents that lived in SHAs. MEASUREMENTS: Nutritional status was examined by
      administering the Mini Nutritional Assessment (MNA). Cognitive status was
      measured by the Mini Mental State Examination (MMSE). RESULTS: Overall, 142
      individuals participated in this study. Statistical analysis showed differences
      in both overall MNA scores and MNA assessment scores. Significantly more
      participants from the SHA setting were at risk of malnutrition compared to the
      home-living setting. CONCLUSION: Screening and assessment of nutritional status
      and prevention interventions should be considered in SHA settings.

PMID- 25389956
TI  - The association of neighborhood characteristics with obesity and metabolic
      conditions in older women.
AB  - OBJECTIVE: Previous studies exploring the relationship of neighborhood
      characteristics with metabolic conditions have focused on middle-aged adults but
      none have comprehensively investigated associations in older adults, a
      potentially vulnerable population. The aim was to explore the relationship of
      neighborhood characteristics with metabolic conditions in older women. DESIGN:
      Cross-sectional analysis. SETTING/PARTICIPANTS: We studied 384 women aged 70-79
      years, representing the two-thirds least disabled women in the community,
      enrolled in the Women's Health and Aging Study II at baseline. Neighborhood
      scores were calculated from census-derived data on median household income,
      median house value, percent earning interest income, percent completing high
      school, percent completing college, and percent with managerial or executive
      occupation. Participants were categorized by quartile of neighborhood score with
      a higher quartile representing relative neighborhood advantage. Logistic
      regression models were created to assess the association of neighborhood
      quartiles to outcomes, adjusting for key covariates. MEASUREMENTS: Primary
      outcomes included metabolic conditions: obesity, diabetes, hypertension, and
      hyperlipidemia. Secondary outcomes included BMI, HbA1c, blood pressure and
      lipids. RESULTS: Higher neighborhood quartile score was associated with a lower
      prevalence of obesity (highest quartile=13.5% versus lowest quartile=36.5%;
      p<0.001 for trend). A lower prevalence of diabetes was also observed in highest
      (6.3%) versus lowest (14.4%) neighborhood quartiles, but was not significantly
      different (p= 0.24 for trend). Highest versus lowest neighborhood quartile was
      associated with lower HbA1c (-0.31%, p=0.02) in unadjusted models. Women in the
      highest versus lowest neighborhood quartile had lower BMI (-2.01 kg/m2, p=0.001)
      and higher HDL-cholesterol (+6.09 mg/dL, p=0.01) after accounting for age, race,
      inflammation, and smoking. CONCLUSION: Worse neighborhood characteristics are
      associated with adiposity, hyperglycemia, and low HDL. Further longitudinal
      studies are needed and can inform future interventions to improve metabolic
      status in older adults.

PMID- 25389954
TI  - Compositional dynamics of the human intestinal microbiota with aging:
      implications for health.
AB  - The human gut contains trillions of microbes which form an essential part of the
      complex ecosystem of the host. This microbiota is relatively stable throughout
      adult life, but may fluctuate over time with aging and disease. The gut
      microbiota serves a number of functions including roles in energy provision,
      nutrition and also in the maintenance of host health such as protection against
      pathogens. This review summarizes the age-related changes in the microbiota of
      the gastrointestinal tract (GIT) and the link between the gut microbiota in
      health and disease. Understanding the composition and function of the gut
      microbiota along with the changes it undergoes overtime should aid the design of
      novel therapeutic strategies to counteract such alterations. These strategies
      include probiotic and prebiotic preparations as well as targeted nutrients,
      designed to enrich the gut microbiota of the aging population. 

PMID- 25389957
TI  - Epigenetic nutraceutical diets in Alzheimer's disease.
AB  - There is growing support that environmental influences and individual genetic
      susceptibility may increase the incidence and accelerate the onset of Alzheimer's
      disease (AD). Epigenetic mechanisms encompass a complex regulatory network of
      modifications with considerable impact on health and disease risk. Abnormal
      epigenetic regulation is a hallmark in many pathological conditions including AD.
      It is well recognized that numerous bioactive dietary components mediate
      epigenetic modifications associated with the pathophysiology of several diseases.
      Although the influences of dietary factors on epigenetic regulation have been
      extensively investigated, only few studies have explored the effects of specific
      food components in regulating epigenetic patterns during neurodegeneration and
      AD. Epigenetic nutritional research has substantial potential for AD and may
      represent a window of opportunity to complement other interventions. Here, we
      provide a brief overview of the main mechanisms involved in AD, some of which may
      be epigenetically modulated by bioactive food. 

PMID- 25389958
TI  - A positive association between stroke risk and sarcopenia in men aged >= 50
      years, but not women: results from the Korean National Health and Nutrition
      Examination Survey 2008-2010.
AB  - BACKGROUND AND AIMS: Sarcopenia, the loss of skeletal muscle mass and strength,
      develops with aging and may be a pivotal risk factor in individual cardiovascular
      diseases (CVDs). We examined whether sarcopenia was positively associated with
      the prevalence of CVDs, including angina pectoris, myocardial infarction, and
      stroke, in adults of each gender aged >=50 years, independent of other covariates
      and possible confounders. METHODS AND RESULTS: This cross-sectional study
      included 3,009 men and 4,199 women aged >=550 years who participated in the 2008
      2010 Korean National Health and Nutrition Examination Survey. Sarcopenia was
      defined as appendicular skeletal muscle mass/body weight <1 (moderate) or 2
      (severe) standard deviations below gender-specific means for young adults. CVD
      prevalence was positively associated with sarcopenia in men after adjusting for
      confounders involved in CVD risk factors (Class I, OR=1.847 and Class II,
      OR=2.347; P<0.05). However, no such association was found in women. Furthermore,
      for individual CVDs, a strong positive association between stroke and sarcopenia
      (Class I, OR=1.734 and Class II, OR=3.725; P<0.05) and a moderate association
      between angina pectoris and sarcopenia (Class I, OR=1.988 and Class II, OR=1.347;
      P<0.05) were observed in men only. Interestingly, only the estimated homeostasis
      model assessment of insulin resistance was greater in men with moderate and
      severe sarcopenia than in those with normal states, whereas only serum total
      cholesterol levels were significantly higher in women with severe sarcopenia than
      in those with normal states. In both genders, serum 25-hydroxyvitamin D levels
      were significantly lower in moderate and severe sarcopenic states. CONCLUSIONS:
      men aged >=50 years with sarcopenia showed elevated prevalence of CVDs,
      especially stroke, in a representative sample of the general South Korean
      population.

PMID- 25389959
TI  - Long-term intermittent glutamine supplementation repairs intestinal damage
      (structure and functional mass) with advanced age: assessment with plasma
      citrulline in a rodent model.
AB  - OBJECTIVE: Glutamine is the preferred fuel for the rat small intestine and
      promotes the growth of intestinal mucosa, especially in the event of gut injury.
      Quantitatively, glutamine is one important precursor for intestinal citrulline
      release. The aim of this study was to determine whether the effect of glutamine
      on the increase in intestinal villus height is correlated with an increase in
      both gut mass and citrulline plasma level in very old rats. METHODS: We
      intermittently supplemented very old (27-mo) female rats with oral glutamine (20%
      of diet protein). Intestinal histomorphometric analysis of the small bowel was
      performed. Amino acids, in particular citrulline, were measured in the plasma,
      liver and jejunum. Markers of renal (creatinine, urea) and liver (alanine
      aminotransferase [ALT]) and aspartate aminotransferase (AST) functions were
      measured to evaluate renal and liver functions in relation to aging and to
      glutamine supplementation. Liver glutathione was also determined to evaluate
      cellular redox state. RESULTS: Glutamine supplementation maintains the body
      weight of very old rats, not by limiting sarcopenia but rather by increasing the
      organ mass of the splanchnic area. Total intestine mass was significantly higher
      in glutamine-supplemented rats than in controls (15%). Measurement of villus
      height and crypt depth demonstrated that the difference between villus and crypt
      was significantly improved in glutamine pre-treated rats compared to controls (~
      11%). Plasma citrulline also increased by 15% in glutamine-supplemented rats
      compared to controls. CONCLUSION: Citrulline appears as a biomarker of enterocyte
      mass in villous atrophy associated with advanced age. Non-invasive measurement of
      this metabolite may be useful in following the state of the gastrointestinal
      tract in very old people, whose numbers are increasing worldwide and the care of
      whom is a major public health issue. The gut may contribute to the malnutrition
      caused by malabsorption frequently observed in the elderly.

PMID- 25389960
TI  - A review of the effects of dietary silicon intake on bone homeostasis and
      regeneration.
AB  - OBJECTIVE: Increasing evidences suggest that dietary Silicon (Si) intake, is
      positively correlated with bone homeostasis and regeneration, representing a
      potential and valid support for the prevention and improvement of bone diseases,
      like osteoporosis. This review, aims to provide the state of art of the studies
      performed until today, in order to investigate and clarify the beneficial
      properties and effects of silicates, on bone metabolism. METHODS: We conducted a
      systematic literature search up to March 2013, using two medical databases
      (Pubmed and the Cochrane Library), to review the studies about Si consumption and
      bone metabolism. RESULTS: We found 45 articles, but 38 were specifically focused
      on Si studies. CONCLUSION: RESULTS showed a positive relationship between dietary
      Si intake and bone regeneration.

PMID- 25389962
TI  - Seven-year predictors of self-rated health and life satisfaction in the elderly:
      the PROOF study.
AB  - OBJECTIVES: To investigate the relationship between cognitive performance,
      affective state, metabolic syndrome and 7-year follow-up self-rated health (SRH)
      and perceived life satisfaction (PLS). DESIGN: Analysis of a prospective cohort
      study. SETTING: The PROOF study, including 1011 elderly community residents.
      PARTICIPANTS: Six hundred and fifty seven subjects completed metabolic syndrome
      (Met S) variables, neuropsychological and affective measurements at baseline, and
      then returned a 7-year follow-up questionnaire which included SRH and PLS.
      MEASUREMENTS: The prospective association between cognitive function, Met S and
      each of its components, and affective disorders and subsequent subjective health
      and quality of life was examined. Covariates included educational level and use
      of tobacco. The analyses were made in men and women separately. RESULTS: In
      multivariate models, the presence of Met S was significantly associated to weaker
      SRH (OR = 2.78, p = 0.009 in men and OR = 2.0, p = 0.02 in women). Higher
      triglycerides rate were associated with weaker SRH in men (OR = 2.23, p = 0.002)
      and higher fasting glucose in women (OR = 2.54, p = 0.006). Global Met S and
      abdominal obesity was significantly associated to weaker PLS in women only
      (respectively OR = 2.70, p = 0.0002 and OR = 1.9, p = 0.02). Depressive symptoms
      were significantly associated to both weaker SRH and PLS in men (OR = 1.30, p =
      0.002; OR = 1.44, p < 0.0001 for SRH and PLS respectively) and in woman (OR =
      1.09, p = 0.04; OR = 1.26, p < 0.0001 for SRH and PLS respectively). Anxiety was
      linked to both weaker SRH and PLS in women (OR = 1.17, p = 0.002 and 0R = 1.11, p
      = 0.03 for SRH and PLS respectively). Finally, lower executive function was
      associated with weaker PLS in men (OR = 0.43, p = 0.0005). CONCLUSION: metabolic
      syndrome and certain of its components, anxiety and depressive symptoms, are
      independent predictors of poorer subjective health and quality of life as
      assessed over a period of 7 years in a population of a non-demented aging
      community. Moreover, executive performance was linked to subsequent quality of
      life in men. Many of these factors being treatable, our findings point to the
      necessity of providing preventive care strategies by the management of
      cardiovascular risk factors and anxio-depressive symptoms.

PMID- 25389963
TI  - Validity and reliability of the Katz-15 scale to measure unfavorable health
      outcomes in community-dwelling older people.
AB  - OBJECTIVES: To predict the risk of future unfavourable health outcomes in older
      people it is common to assess the level of both basic and instrumental activities
      of daily living. To accomplish this, the commonly used Katz-6 and the Lawton IADL
      questionnaires can be combined to form the 'Modified Katz ADL' scale, also known
      as the Katz-15 scale. So far, the validity and reliability of the Katz-15 scale
      is unknown. The objective of the current study is to investigate how well the
      Katz-15 is able to predict future unfavorable health outcomes and how this is
      related to the existing Katz-6 scale. DESIGN: We performed a follow-up study
      using data from a group of 60 year and older participants from a large Dutch
      clinical trial. PARTICIPANTS: We included 2321 participants in the analysis. The
      average age of the study population was 74 years and 44% was male. MEASUREMENTS:
      We studied the relation between the Katz-15 scale and a number of unfavourable
      health outcomes, such as hospitalization, admission to a nursing home, admission
      to a home for the aged and death within one year of follow-up. RESULTS: We found
      the Katz-15 to be both internally consistent and strongly associated with quality
      of life measures. We observed moderate to strong associations between the Katz-15
      and the unfavourable health outcomes All associations studied were stronger for
      the Katz-15 scale as compared to the Katz-6 scale. CONCLUSION: The results of our
      study indicate that the Katz-15 scale is able to reliably and validly predict
      future unfavorable health outcomes. This makes the scale a valuable measure in
      determining both basic and instrumental activities of daily living.

PMID- 25389961
TI  - Inverse association between dietary habits with high total antioxidant capacity
      and prevalence of frailty among elderly Japanese women: a multicenter cross
      sectional study.
AB  - OBJECTIVE: To examine the association of dietary habits with high total
      antioxidant capacity (TAC) with frailty among elderly Japanese women. DESIGN:
      Cross-sectional multicenter study. SETTING: Thirty-five of 47 prefectures in
      Japan. PARTICIPANTS: 2121 grandmothers or acquaintances of dietetic students aged
      65 and older. MEASUREMENTS: Dietary TAC and food intakes were calculated using a
      validated brief-type self-administered diet history questionnaire. The TAC value
      of each food was assigned using four different assays, ferric reducing ability of
      plasma (FRAP), oxygen radical absorbance capacity (ORAC), Trolox equivalent
      antioxidant capacity (TEAC), and total radical-trapping antioxidant parameter
      (TRAP). Frailty was defined as the presence three or more of the following four
      components: slowness and weakness (two points), exhaustion, low physical
      activity, and unintentional weight loss. RESULTS: The number of subjects with
      frailty was 486 (23%). Multivariate adjusted ORs (95% CI) for frailty in the
      highest compared to the lowest quintile were 0.35 (0.24, 0.53) for FRAP, 0.35
      (0.23, 0.52) for ORAC, 0.40 (0.27, 0.60) for TEAC, and 0.41 (0.28, 0.62) for
      TRAP. The intakes of green tea, coffee, vegetables, and fruits which contribute
      to dietary TAC were also associated with lower odds of frailty (the range of
      multivariate adjusted OR: 0.47 for vegetables to 0.77 for green tea), although
      the odds ratios were less marked than those of dietary TAC. CONCLUSIONS: Dietary
      habits with high TAC showed a stronger inverse association with frailty in
      elderly Japanese women than the individual foods examined.

PMID- 25389964
TI  - Recipient-related risk factors for graft failure and death in elderly kidney
      transplant recipients.
AB  - BACKGROUND: Elderly patients with end-stage renal disease have become the fastest
      growing population of kidney transplant candidates in recent years. However, the
      risk factors associated with long-term outcomes in these patients remain unclear.
      METHODS: We retrospectively analyzed 166 recipients aged 60 years or older who
      underwent primary deceased kidney transplantation between 2002 and 2013 in our
      center. The main outcomes included 1-, 3- and 5-year patient survival as well as
      overall and death-censored graft survival. The independent risk factors affecting
      graft and patient survival were analyzed using Cox regression analysis. RESULTS:
      The 1-, 3-, 5-year death-censored graft survival rates were 93.6%, 89.4% and
      83.6%, respectively. Based on the Cox multivariate analysis, panel reactive
      antibody (PRA)>5% [hazard ratio (HR) 4.295, 95% confidence interval (CI) 1.321
      13.97], delayed graft function (HR 4.744, 95% CI 1.611-13.973) and acute
      rejection (HR 4.971, 95% CI 1.516-16.301) were independent risk factors for graft
      failure. The 1-, 3-, 5-year patient survival rates were 84.8%, 82.1% and 77.1%,
      respectively. Longer dialysis time (HR 1.011 for 1-month increase, 95% CI 1.002
      1.020), graft loss (HR 3.501, 95% CI 1.559-7.865) and low-dose ganciclovir
      prophylaxis (1.5 g/d for 3 months) (HR 3.173, 95% CI 1.063-9.473) were risk
      factors associated with patient death. CONCLUSIONS: The five-year results show an
      excellent graft and patient survival in elderly kidney transplant recipients aged
      >=60 years. PRA>5%, delayed graft function, and acute rejection are risk factors
      for graft failure, while longer duration of dialysis, graft loss and low-dose
      ganciclovir prophylaxis are risk factors for mortality in elderly recipients.
      These factors represent potential targets for interventions aimed at improving
      graft and patient survival in elderly recipients.

PMID- 25389965
TI  - The effect of 3D nanofibrous scaffolds on the chondrogenesis of induced
      pluripotent stem cells and their application in restoration of cartilage defects.
AB  - The discovery of induced pluripotent stem cells (iPSCs) rendered the
      reprogramming of terminally differentiated cells to primary stem cells with
      pluripotency possible and provided potential for the regeneration and restoration
      of cartilage defect. Chondrogenic differentiation of iPSCs is crucial for their
      application in cartilage tissue engineering. In this study we investigated the
      effect of 3D nanofibrous scaffolds on the chondrogenesis of iPSCs and articular
      cartilage defect restoration. Super-hydrophilic and durable mechanic
      polycaprolactone (PCL)/gelatin scaffolds were fabricated using two separate
      electrospinning processes. The morphological structure and mechanical properties
      of the scaffolds were characterized. The chondrogenesis of the iPSCs in vitro and
      the restoration of the cartilage defect was investigated using scanning electron
      microscopy (SEM), the Cell Counting Kit-8 (CCK-8), histological observation, RT
      qPCR, and western blot analysis. iPSCs on the scaffolds expressed higher levels
      of chondrogenic markers than the control group. In an animal model, cartilage
      defects implanted with the scaffold-cell complex exhibited an enhanced gross
      appearance and histological improvements, higher cartilage-specific gene
      expression and protein levels, as well as subchondral bone regeneration.
      Therefore, we showed scaffolds with a 3D nanofibrous structure enhanced the
      chondrogenesis of iPSCs and that iPSC-containing scaffolds improved the
      restoration of cartilage defects to a greater degree than did scaffolds alone in
      vivo. 

PMID- 25389967
TI  - New species of Rotundomys (Cricetinae) from the Late Miocene of Spain and its
      bearing on the phylogeny of Cricetulodon and Rotundomys.
AB  - The material of Rotundomys (Rodentia, Cricetinae) from the Late Miocene
      fossiliferous complex of Cerro de los Batallones (Madrid, Spain) is described and
      compared with all species currently placed in the genera Rotundomys and
      Cricetulodon. Both the morphology and size variation encompassed in the
      collection of specimens from Batallones suggest they belong to a single taxon
      different from the other known species of these genera. A new species Rotundomys
      intimus sp. nov. is, therefore, named for it. A cladistic analysis, which is the
      first ever published concernig these taxa, has been conducted to clear up the
      phylogenetic position of the new species. Our results suggest that Rotundomys
      intimus sp. nov. inserts between R. mundi and R. sabatieri as a relatively
      primitive taxon inside the clade Rotundomys. The new taxon is more derived than
      R. mundi in having a transversal connection between the metalophulid and the
      anterolophulid on some m1 but more primitive than R. sabatieri and the most
      evolved species of Rotundomys (R. montisrotuni +R.bressanus) in its less
      developed lophodonty showing distinct cusps, shallower valleys, and the presence
      of a subdivided anteroloph on the M1. The species of Cricetulodon do not form a
      monophyletic group. As a member of Rotundomys, Rotundomys intimus sp. nov. is
      more derived than all of these taxa in its greater lophodonty and the complete
      loss of the anterior protolophule, mesolophs, and mesolophids. 

PMID- 25389966
TI  - The circadian clock maintains cardiac function by regulating mitochondrial
      metabolism in mice.
AB  - Cardiac function is highly dependent on oxidative energy, which is produced by
      mitochondrial respiration. Defects in mitochondrial function are associated with
      both structural and functional abnormalities in the heart. Here, we show that
      heart-specific ablation of the circadian clock gene Bmal1 results in cardiac
      mitochondrial defects that include morphological changes and functional
      abnormalities, such as reduced enzymatic activities within the respiratory
      complex. Mice without cardiac Bmal1 function show a significant decrease in the
      expression of genes associated with the fatty acid oxidative pathway, the
      tricarboxylic acid cycle, and the mitochondrial respiratory chain in the heart
      and develop severe progressive heart failure with age. Importantly, similar
      changes in gene expression related to mitochondrial oxidative metabolism are also
      observed in C57BL/6J mice subjected to chronic reversal of the light-dark cycle;
      thus, they show disrupted circadian rhythmicity. These findings indicate that the
      circadian clock system plays an important role in regulating mitochondrial
      metabolism and thereby maintains cardiac function. 

PMID- 25389971
TI  - Spatial distribution of oak mistletoe as it relates to habits of oak woodland
      frugivores.
AB  - This study addresses the underlying spatial distribution of oak mistletoe,
      Phoradendron villosum, a hemi-parasitic plant that provides a continuous supply
      of berries for frugivorous birds overwintering the oak savanna habitat of
      California's outer coast range. As the winter community of birds consuming oak
      mistletoe varies from group-living territorial species to birds that roam in
      flocks, we asked if mistletoe volume was spatially autocorrelated at the scale of
      persistent territories or whether the patterns predicted by long-term territory
      use by western bluebirds are overcome by seed dispersal by more mobile bird
      species. The abundance of mistletoe was mapped on trees within a 700 ha study
      site in Carmel Valley, California. Spatial autocorrelation of mistletoe volume
      was analyzed using the variogram method and spatial distribution of oak mistletoe
      trees was analyzed using Ripley's K and O-ring statistics. On a separate set of
      45 trees, mistletoe volume was highly correlated with the volume of female, fruit
      bearing plants, indicating that overall mistletoe volume is a good predictor of
      fruit availability. Variogram analysis showed that mistletoe volume was spatially
      autocorrelated up to approximately 250 m, a distance consistent with persistent
      territoriality of western bluebirds and philopatry of sons, which often breed
      next door to their parents and are more likely to remain home when their parents
      have abundant mistletoe. Using Ripley's K and O-ring analyses, we showed that
      mistletoe trees were aggregated for distances up to 558 m, but for distances
      between 558 to 724 m the O-ring analysis deviated from Ripley's K in showing
      repulsion rather than aggregation. While trees with mistletoe were aggregated at
      larger distances, mistletoe was spatially correlated at a smaller distance,
      consistent with what is expected based on persistent group territoriality of
      western bluebirds in winter and the extreme philopatry of their sons. 

PMID- 25389968
TI  - A polymeric prodrug of 5-fluorouracil-1-acetic acid using a multi-hydroxyl
      polyethylene glycol derivative as the drug carrier.
AB  - PURPOSE: Macromolecular prodrugs obtained by covalently conjugating small
      molecular drugs with polymeric carriers were proven to accomplish controlled and
      sustained release of the therapeutic agents in vitro and in vivo. Polyethylene
      glycol (PEG) has been extensively used due to its low toxicity, low
      immunogenicity and high biocompatibility. However, for linear PEG macromolecules,
      the number of available hydroxyl groups for drug coupling does not change with
      the length of polymeric chain, which limits the application of PEG for drug
      conjugation purposes. To increase the drug loading and prolong the retention time
      of 5-fluorouracil (5-Fu), a macromolecular prodrug of 5-Fu, 5-fluorouracil-1 acid
      PAE derivative (5-FA-PAE) was synthesized and tested for the antitumor activity
      in vivo. METHODS: PEG with a molecular weight of 38 kDa was selected to
      synthesize the multi-hydroxyl polyethylene glycol derivative (PAE) through an
      addition reaction. 5-fluorouracil-1 acetic acid (5-FA), a 5-Fu derivative was
      coupled with PEG derivatives via ester bond to form a macromolecular prodrug, 5
      FA-PAE. The in vitro drug release, pharmacokinetics, in vivo distribution and
      antitumor effect of the prodrug were investigated, respectively. RESULTS: The PEG
      based prodrug obtained in this study possessed an exceedingly high 5-FA loading
      efficiency of 10.58%, much higher than the maximum drug loading efficiency of
      unmodified PEG with the same molecular weight, which was 0.98% theoretically.
      Furthermore, 5-FA-PAE exhibited suitable sustained release in tumors. CONCLUSION:
      This study provides a new approach for the development of the delivery to tumors
      of anticancer agents with PEG derivatives.

PMID- 25389972
TI  - Divergence in male and female manipulative behaviors with the intensification of
      metallurgy in Central Europe.
AB  - Humeral morphology has been shown to reflect, in part, habitual manipulative
      behaviors in humans. Among Central European agricultural populations, long-term
      social change, increasing task specialization, and technological innovation all
      had the potential to impact patterns of habitual activity and upper limb
      asymmetry. However, systematic temporal change in the skeletal morphology of
      agricultural populations in this region has not been well-characterized. This
      study investigates diachronic patterns in humeral biomechanical properties and
      lengths among 174 adult Central European agriculturalists through the first ~
      5400 years of farming in the region. Greater asymmetry in biomechanical
      properties was expected to accompany the introduction of metallurgy, particularly
      in males, while upper limb loading patterns were expected to be more similar
      between the Bronze and Iron Ages. Results revealed a divergence in the
      lateralization of upper limb biomechanical properties by sex between the
      Early/Middle Neolithic and Early/Middle Bronze Age. Neolithic females had
      significantly more variable properties than males in both humeri, while Bronze
      Age female properties became homogeneous and very symmetrical relative to the
      right-biased lateralization of contemporaneous males. The Bronze Age to Iron Age
      transition was associated with morphological change among females, with a
      significant increase in right-biased asymmetry and a concomitant reduction in
      sexual dimorphism. Relative to biomechanical properties, humeral length variation
      and asymmetry were low though some significant sexual dimorphism and temporal
      change was found. It was among females that the lateralization of humeral
      biomechanical properties, and variation within them, changed most profoundly
      through time. This suggests that the introduction of the ard and plow,
      metallurgical innovation, task specialization, and socioeconomic change through ~
      5400 years of agriculture impacted upper limb loading in Central European women
      to a greater extent than men.

PMID- 25389973
TI  - IL28B polymorphism cannot predict response to interferon alpha treatment in
      patients with melanoma.
AB  - BACKGROUND: Recent genome-wide association studies revealed the rs12979860 single
      nucleotide polymorphism (SNP) of the IL28B gene (CC genotype) to be the strongest
      pre-therapeutic predictor of therapy response to interferon alpha in patients
      with chronic hepatitis C infection. The favorable CC genotype is associated with
      significantly higher rates of sustained virologic response. No data exist on the
      role of IL28B polymorphism in interferon therapy of diseases other than viral
      hepatitis. METHODS: A retrospective study involving 106 patients with melanoma
      who received low- or high-dose interferon therapy was performed. The CC and non
      CC genotype of IL28B rs12979860 SNP were correlated with progression-free and
      overall survival. RESULTS: 44 (41.5%) patients were CC and 62 (58.5%) non-CC.
      There was no statistically significant difference in age at diagnosis, melanoma
      type or localization, Breslow level or AJCC stage between CC and non-CC patients.
      During the observation period (6.43+/-4.66 years) disease progression occurred in
      36 (34%) patients after 5.5+/-4.3 years. 43.2% (19) of patients with CC and 27.4%
      (17) of patients with non-CC genotype were affected (p = 0.091). Disease
      progression was more frequent in patients on high dose interferon therapy and
      with a worse AJCC stage. CONCLUSION: In contrast to classical risk factors like
      tumor thickness and clinical stage, IL28B polymorphism was not associated with
      progression-free or overall survival in patients with melanoma treated with
      interferon alpha.

PMID- 25389974
TI  - Crucial role for neuronal nitric oxide synthase in early microcirculatory
      derangement and recipient survival following murine pancreas transplantation.
AB  - OBJECTIVE: Aim of this study was to identify the nitric oxide synthase (NOS)
      isoform involved in early microcirculatory derangements following solid organ
      transplantation. BACKGROUND: Tetrahydrobiopterin donor treatment has been shown
      to specifically attenuate these derangements following pancreas transplantation,
      and tetrahydrobiopterin-mediated protective effects to rely on its NOS-cofactor
      activity, rather than on its antioxidant capacity. However, the NOS-isoform
      mainly involved in this process has still to be defined. METHODS: Using a murine
      pancreas transplantation model, grafts lacking one of the three NOS-isoforms were
      compared to grafts from wild-type controls. Donors were treated with either
      tetrahydrobiopterin or remained untreated. All grafts were subjected to 16 h cold
      ischemia time and transplanted into wild-type recipients. Following 4 h graft
      reperfusion, microcirculation was analysed by confocal intravital fluorescence
      microscopy. Recipient survival was monitored for 50 days. RESULTS:
      Transplantation of the pancreas from untreated wild-type donor mice resulted in
      microcirculatory damage of the transplanted graft and no recipient survived more
      than 72 h. Transplanting grafts from untreated donor mice lacking either
      endothelial or inducible NOS led to similar outcomes. In contrast, donor
      treatment with tetrahydrobiopterin prevented microcirculatory breakdown enabling
      long-term survival. Sole exception was transplantation of grafts from untreated
      donor mice lacking neuronal NOS. It resulted in intact microvascular structure
      and long-term recipient survival, either if donor mice were untreated or treated
      with tetrahydrobiopterin. CONCLUSION: We demonstrate for the first time the
      crucial involvement of neuronal NOS in early microcirculatory derangements
      following solid organ transplantation. In this model, protective effects of
      tetrahydrobiopterin are mediated by targeting this isoform.

PMID- 25389975
TI  - In vitro antibacterial activity of a novel resin-based pulp capping material
      containing the quaternary ammonium salt MAE-DB and Portland cement.
AB  - BACKGROUND: Vital pulp preservation in the treatment of deep caries is
      challenging due to bacterial infection. The objectives of this study were to
      synthesize a novel, light-cured composite material containing bioactive calcium
      silicate (Portland cement, PC) and the antimicrobial quaternary ammonium salt
      monomer 2-methacryloxylethyl dodecyl methyl ammonium bromide (MAE-DB) and to
      evaluate its effects on Streptococcus mutans growth in vitro. METHODS: The
      experimental material was prepared from a 2 : 1 ratio of PC mixed with a resin of
      2-hydroxyethylmethacrylate, bisphenol glycerolate dimethacrylate, and triethylene
      glycol dimethacrylate (4 : 3 : 1) containing 5 wt% MAE-DB. Cured resin containing
      5% MAE-DB without PC served as the positive control material, and resin without
      MAE-DB or PC served as the negative control material. Mineral trioxide aggregate
      (MTA) and calcium hydroxide (Dycal) served as commercial controls. S. mutans
      biofilm formation on material surfaces and growth in the culture medium were
      tested according to colony-forming units (CFUs) and metabolic activity after 24 h
      incubation over freshly prepared samples or samples aged in water for 6 months.
      Biofilm formation was also assessed by Live/Dead staining and scanning electron
      microscopy. RESULTS: S. mutans biofilm formation on the experimental material was
      significantly inhibited, with CFU counts, metabolic activity, viability staining,
      and morphology similar to those of biofilms on the positive control material.
      None of the materials affected bacterial growth in solution. Contact-inhibition
      of biofilm formation was retained by the aged experimental material. Significant
      biofilm formation was observed on MTA and Dycal. CONCLUSION: The synthesized
      material containing HEMA-BisGMA-TEGDMA resin with MAE-DB as the antimicrobial
      agent and PC to support mineralized tissue formation inhibited S. mutans biofilm
      formation even after aging in water for 6 months, but had no inhibitory effect on
      bacteria in solution. Therefore, this material shows promise as a pulp capping
      material for vital pulp preservation in the treatment of deep caries.

PMID- 25389976
TI  - Brain structural correlates of risk-taking behavior and effects of peer influence
      in adolescents.
AB  - Adolescents are characterized by impulsive risky behavior, particularly in the
      presence of peers. We discriminated high and low risk-taking male adolescents
      aged 18-19 years by assessing their propensity for risky behavior and
      vulnerability to peer influence with personality tests, and compared structural
      differences in gray and white matter of the brain with voxel-based morphometry
      (VBM) and diffusion tensor imaging (DTI), respectively. We also compared the
      brain structures according to the participants' actual risk-taking behavior in a
      simulated driving task with two different social conditions making up a peer
      competition situation. There was a discrepancy between the self-reported
      personality test results and risky driving behavior (running through an
      intersection with traffic lights turning yellow, chancing a collision with
      another vehicle). Comparison between high and low risk-taking adolescents
      according to personality test results revealed no significant difference in gray
      matter volume and white matter integrity. However, comparison according to actual
      risk-taking behavior during task performance revealed significantly higher white
      matter integrity in the high risk-taking group, suggesting that increased risky
      behavior during adolescence is not necessarily attributed to the immature brain
      as conventional wisdom says. 

PMID- 25389977
TI  - Preparation of spherical calcium phosphate granulates suitable for the
      biofunctionalization of active brazed titanium alloy coatings.
AB  - Titanium-based alloys can be actively brazed onto bio-inert ceramics and
      potentially be used as biocompatible coatings. To further improve their
      bioactivity in vivo, introduction of calcium phosphate (CaP)-based granulates
      onto their surface layer is possible. For this, mechanically stable CaP-based
      granulates need to be able to withstand the demand of the brazing process. In
      this study, spherical granulates, made of a calcium phosphate composite composed
      primarily of beta-tricalcium phosphate and hydroxyapatite, a bioactive glass, and
      a mixture of the previous two, were manufactured by spray drying. The influence
      of organic additives (Dolapix CE64, trisodium citrate) and solids content (30-80
      wt%) in the slurry on the physical characteristics of granulates was
      investigated. X-ray diffraction, Brunauer, Emmett, Teller specific surface area
      standard method, scanning electron microscopy, granulate size analysis, and
      single granule strength were performed. Our results showed that trisodium citrate
      permitted the production of granulates with regular morphology, high density, and
      increased failure stress values. The strong granules also withstood the brazing
      process. These results show that CaP bioactive agents can be generated and be
      integrated during the demanding metallurgical processes, allowing for one-step
      bioactivation of metal brazes. 

PMID- 25389978
TI  - Measurement of the axial and circumferential mechanical properties of rat skin
      tissue at different anatomical locations.
AB  - Skin tissue is not only responsible for thermoregulation but also for protecting
      the human body from mechanical, bacterial, and viral insults. The mechanical
      properties of skin tissue may vary according to the anatomical locations in the
      body. However, the linear elastic and nonlinear hyperelastic mechanical
      properties of the skin in different anatomical regions and at different loading
      directions (axial and circumferential) so far have not been determined. In this
      study, the mechanical properties during tension of the rat abdomen and back were
      calculated at different loading directions using linear elastic and nonlinear
      hyperelastic material models. The skin samples were subjected to a series of
      tensile tests. The elastic modulus and maximum stress of the skin tissues were
      measured before the incidence of failure. The nonlinear mechanical behavior of
      the skin tissues was also computationally investigated through a constitutive
      equation. Hyperelastic strain energy density function was calibrated using the
      experimental data. The results revealed the anisotropic mechanical behavior of
      the abdomen and the isotropic mechanical response of the back skin. The highest
      elastic modulus was observed in the abdomen skin under the axial direction (10
      MPa), while the lowest one was seen in the back skin under axial loading (5 MPa).
      The Mooney-Rivlin material model closely addressed the nonlinear mechanical
      behavior of the skin at different loading directions, which can be implemented in
      the future biomechanical models of skin tissue. The results might have
      implications not only for understanding of the isotropic and anisotropic
      mechanical behavior of skin tissue at different anatomical locations but also for
      providing more information for a diversity of disciplines, including dermatology,
      cosmetics industry, clinical decision making, and clinical intervention. 

PMID- 25389979
TI  - Evaluation of a novel noninvasive continuous core temperature measurement system
      with a zero heat flux sensor using a manikin of the human body.
AB  - Reliable continuous perioperative core temperature measurement is of major
      importance. The pulmonary artery catheter is currently the gold standard for
      measuring core temperature but is invasive and expensive. Using a manikin, we
      evaluated the new, noninvasive SpotOnTM temperature monitoring system (SOT). With
      a sensor placed on the lateral forehead, SOT uses zero heat flux technology to
      noninvasively measure core temperature; and because the forehead is devoid of
      thermoregulatory arteriovenous shunts, a piece of bone cement served as a model
      of the frontal bone in this study. Bias, limits of agreements, long-term
      measurement stability, and the lowest measurable temperature of the device were
      investigated. Bias and limits of agreement of the temperature data of two SOTs
      and of the thermistor placed on the manikin's surface were calculated.
      Measurements obtained from SOTs were similar to thermistor values. The bias and
      limits of agreement lay within a predefined clinically acceptable range. Repeat
      measurements differed only slightly, and stayed stable for hours. Because of its
      temperature range, the SOT cannot be used to monitor temperatures below 28
      degrees C. In conclusion, the new SOT could provide a reliable, less invasive and
      cheaper alternative for measuring perioperative core temperature in routine
      clinical practice. Further clinical trials are needed to evaluate these results.

PMID- 25389980
TI  - Effect of blood on ROM diagnosis accuracy of PAMG-1 and IGFBP-1 detecting rapid
      tests.
AB  - Vaginal bleeding may be present in up to 30% of patients presenting with signs
      and symptoms of a rupture of the fetal membranes (ROM). The presence of blood may
      lead to false positive results with biochemical markers. The data presented in
      this study came from a multi-centric prospective observational clinical study
      that, for the first time, systematically evaluated the performance of placental
      alpha microglobulin-1 (PAMG-1) and insulin-like growth factor binding protein-1
      (IGFBP-1) detecting tests in 151 women with vaginal bleedings as well as signs
      and symptoms indicative of ROM. Our data showed better performance for the PAMG-1
      compared with the IGFBP-1 detecting tests in all quality parameters evaluated. In
      detail, sensitivity (SN) was 97.8% (91.0%), specificity (SP) was 91.5% (75.0%),
      positive predictive value (PPV) was 94.6% (83.5%) and negative predictive value
      (NPV) was 96.4% (85.7%) for PAMG-1 tests (and IGFBP-1 tests, respectively). A
      major difference between both tests was related to the number of non-evaluable
      test results (e.g., hidden bands due to blood smear on the test strips). While 2%
      of all results were not evaluable for PAMG-1 tests, this artifact appeared in 11%
      of the results obtained with IGFBP-1 tests. This difference and also those in
      Specificity and PPV were statistically significant, demonstrating superiority of
      PAMG-1 over IGFBP-1 detecting tests. In conclusion, the PAMG-1 detecting test was
      significantly less susceptible to interference by blood than the IGFBP-1
      detecting test. 

PMID- 25389981
TI  - Is pharmacologic research on pregnant women with psychoses ethically permissible?
AB  - There is a consistent view in the literature that research on pregnant woman with
      psychoses is ethically questionable or impermissible. This paper provides a
      critical appraisal of these views by asking whether pharmacologic research on
      pregnant women with psychosis for maternal, fetal, and newborn benefit is
      ethically permissible. We examine separately the documented clinical benefits and
      risks to the pregnant patient, the fetal patient, and the neonatal and pediatric
      patient. The outcomes reported in the pertinent literature do not support the
      conclusion that pharmacologic management of psychosis during pregnancy results in
      documented, unacceptable risk to the pregnant, fetal, or neonatal patient and is
      therefore ethically ruled out. Claims that research on the pharmacologic
      management of psychosis during pregnancy is ethically impermissible because of
      unacceptable risk of harm to pregnant, fetal, neonatal, or pediatric patients
      cannot therefore be supported. Having shown that such research is permissible, we
      then ask what ethical considerations should guide study design. We show that
      Phase I studies are appropriate and can meet the requirements of the Common Rule,
      which are more specific than international guidance. As a matter of
      professionally responsible obstetric practice, pregnant women with psychoses
      should be included, and not be neglected, in research for both maternal and fetal
      benefit. 

PMID- 25389982
TI  - The interplay between maternal obesity and gestational diabetes mellitus.
AB  - There is a strong epidemiological association between maternal obesity and
      gestational diabetes mellitus (GDM). Since the publication of the Hyperglycemia
      and Adverse Pregnancy Outcome (HAPO) study on women with mild hyperglycemia in
      2008, new criteria have been introduced in maternity services internationally for
      the diagnosis of GDM. As a result, the diagnosis of GDM may be made in one-third
      of obese women (n=68). The aim of this review was to examine the interplay
      between maternal obesity and GDM in light of the HAPO study and the subsequent
      revised diagnostic criteria. Obesity and GDM are important obstetric risk factors
      because they both are potentially modifiable. However, the new international
      criteria for the diagnosis of GDM have serious resource implications for
      maternity services provided to the large number of women attending for care in
      developed countries. Further consideration needs to be given as to whether obese
      women with mild hyperglycemia need to be referred to a multidisciplinary team
      antenatally if they do not require insulin treatment. 

PMID- 25389983
TI  - Uterine rupture after the uterine fundal pressure maneuver.
AB  - OBJECTIVE: To clarify the incidence of uterine fundal pressure at delivery and
      its effect on uterine rupture. STUDY DESIGN: A questionnaire was sent to 2518
      institutions in Japan. We received a response from 1430. RESULTS: Of reporting
      institutions, 89.4% used fundal pressure in at least some of their deliveries.
      Among the 347,771 women who delivered vaginally in this study, 38,973 (11.2%)
      were delivered with the assistance of fundal pressure. There were six cases of
      uterine rupture associated with uterine fundal pressure, with one case resulting
      in maternal death secondary to amniotic fluid embolism. CONCLUSION: Since uterine
      fundal pressure may potentially cause serious injury to either the mother and/or
      neonates, the indications for application need to be clearly elucidated, and
      obstetric care providers also need comprehensive education and training.

PMID- 25389984
TI  - The unborn smoker: association between smoking during pregnancy and adverse
      perinatal outcomes.
AB  - OBJECTIVE: To evaluate a possible dose-response relationship between active
      maternal smoking during pregnancy and adverse perinatal outcome. DESIGN:
      Retrospective cohort study. SETTING: Population-based in Montreal, Quebec,
      Canada. POPULATION: Women who gave birth to a liveborn or stillborn infant during
      the period of January 2001 to December 2007. METHODS: Active smokers of different
      daily cigarette consumption (n=1646) were identified through maternal self
      reporting. The reference group comprised 19,292 non-smoking women who delivered
      during the same period. MAIN OUTCOME MEASURES: Birth weight, preterm delivery
      rate, fetal and neonatal mortality and morbidity, and congenital malformations.
      RESULTS: Preterm delivery rate was significantly higher in the smoking group
      compared with controls (22.2% vs. 12.4%, P<0.05), as was intrauterine fetal
      demise (1.4% vs. 0.3%, P<0.05). Newborns of active smokers were more likely to
      weigh less (3150+/-759 g vs. 3377+/-604 g, P<0.05), suffer from respiratory
      distress syndrome (2.5% vs. 1.3%, P<0.05), suffer from a cardiac malformation
      (1.5% vs. 0.8%, P<0.05), and die (neonatal death 1.2% vs. 0.6%, P<0.05). A dose
      response relationship was demonstrated between levels of daily cigarette smoking
      and several adverse outcomes. Using multiple regression models, smoking was found
      to be an independent predictor of preterm delivery (odds ratios (OR) 1.9, 95%
      confidence intervals (95%CI) 1.6-2), and intrauterine fetal demise (OR 2.4, 95%CI
      1.4-4.2). CONCLUSION: Any amount of daily smoking appears to harm the fetus and
      newborn. As pregnancy may be a "window of opportunity" for behavioural changes,
      efforts to promote smoking cessation should be encouraged.

PMID- 25389985
TI  - A role for psychiatry in parental override cases.

PMID- 25389986
TI  - Victimization exposure and suicidal ideation among Spaniard adolescents evaluated
      at outpatient mental health services.
AB  - Suicidal ideation among adolescents has been associated with victimization in
      various studies; however, the nature of this association is not clear. Our aim
      was to examine the influence of victimization exposure on suicidal ideation in a
      clinical sample of adolescents. Eleven to 17-year-old subjects were recruited
      from Child and Adolescent Outpatient Psychiatric Services. They completed the
      Self-Injurious Thoughts and Behaviors Interview, the Stressful Life Events Scale,
      the State-Trait Anger Expression Inventory, the Children's Depression Inventory,
      the Strengths and Difficulties Questionnaire, and the Family APGAR. Demographic
      data, developmental features, medical and psychiatric history, family history,
      and treatment histories were also evaluated. A backward stepwise logistic
      regression analysis was conducted to examine the influence of victimization
      exposure on suicidal ideation controlling for potential confounding variables.
      Two hundred and thirty-nine adolescents (62.3% male; mean age 14.31 years,
      SD=1.9) took part in this investigation. Of these, 20.9% reported victimization
      exposure. Adolescents who experienced peer victimization and/or were victims of a
      crime were significantly more likely to report suicidal ideation (chi2=10.05,
      df=1, p=0.002). However, suicidal ideation was only predicted by emotional and
      behavioral problems (chi2=4.79, df=1, p=0.029), depressive sympthomatology
      (chi2=3.17, df=1, p=0.075), and number of total stressful life events (chi2=4.02,
      df=1, p=0.045). Behavioral and emotional problems, as well as the accumulation of
      stressful life events may have a direct relation to suicidal ideation among
      adolescents evaluated at Child and Adolescent Mental Health Outpatient Services.
      Future studies might consider a comprehensive assessment of victimization and the
      cumulative effects of exposure to multiple stressful life events. Longitudinal
      designs are warranted. 

PMID- 25389987
TI  - Dynamic changes in the hypothalamic-pituitary-adrenal axis during growth hormone
      therapy in children with growth hormone deficiency: a multicenter retrospective
      study.
AB  - OBJECTIVE: The objective of this study was to investigate changes in the
      hypothalamic-pituitary-adrenal (HPA) axis after recombinant human growth hormone
      (rhGH) therapy. SUBJECTS: Subjects included children with growth hormone
      deficiency (GHD). METHODS: We conducted a multicenter, retrospective study that
      assessed 72 GHD patients treated with rhGH during 6 months. Patients were
      classified into two groups: isolated GHD (IGHD; n=20) and multiple pituitary
      hormone deficiencies (MPHD; n=52). The HPA axis and other hormones were evaluated
      at baseline and every 3 months. RESULTS: In the MPHD group, 32 patients had
      adrenocorticotrophic hormone deficiency and received hydrocortisone before rhGH
      therapy. In the other 20/52 MPHD patients, the cortisol (COR) level was
      significantly reduced after rhGH therapy. Moreover, 10 patients showed low COR
      levels. In the IGHD group, COR levels also decreased, but remained within the
      normal range. CONCLUSION: During rhGH therapy, COR levels were reduced,
      particularly in patients with MPHD. HPA axis should be monitored during rhGH
      therapy.

PMID- 25389988
TI  - Childhood obesity and eating behaviour.
AB  - The prevalence of childhood obesity has increased substantially in the recent
      decade as a result of the reduction in physical activity and the availability of
      high-fat and high-energy-density foods which the paediatric population faces
      daily. Although children are highly exposed to these foods, there is a wide
      variation in body weight, suggesting the presence of different patterns of
      response to an "obesogenic" environment. This wide variability from the point of
      view of eating behaviour involves a number of social issues (e.g., food
      availability, cost) as well as genuine behavioural traits such as the response to
      satiety, energy compensation, eating rate, responsiveness to food, food reward
      and dietary preferences. This article reviews the main physiological variables
      related to energy intake affecting eating behaviour in the paediatric population.

PMID- 25389989
TI  - Turner syndrome patients with bicuspid aortic valves and renal malformations
      exhibit abnormal expression of X-linked inhibitor of apoptosis protein (XIAP).
AB  - OBJECTIVE: We analyzed mRNA expression of X-linked inhibitor of apoptosis protein
      (XIAP) in patients with Turner syndrome (TS) and examined its association with
      phenotypic features. SUBJECTS AND METHODS: XIAP mRNA expression levels were
      investigated in 98 patients with TS in total RNA extracted from blood leucocytes
      by real time quantitative polymerase chain reaction. RESULTS: Levels of XIAP mRNA
      were significantly lower in patients with bicuspid aortic valves (BAV; n=13) than
      those without (log XIAP -1.17+/-0.3 vs. -0.94+/-0.2, p=0.002). Significantly
      higher expression of XIAP mRNA was seen in patients with a mosaic karyotype and
      renal malformations (log XIAP -0.79+/-0.3 vs. -1.0+/-0.3, p=0.03). No
      correlations were seen between XIAP and other manifestations. CONCLUSION:
      Abnormal expression of XIAP may be an important underlying mechanism in the
      development of BAV and renal malformations in TS. However, abnormal XIAP mRNA
      expression, as determined from peripheral mononuclear cells, does not appear to
      explain all the somatic and visceral stigmata of TS.

PMID- 25389990
TI  - Comparison of cortisol samples in the first two weeks of life in preterm infants.
AB  - BACKGROUND: Growing literature on negative childhood stress emphasizes the need
      to understand cortisol values from varying biomarker samples. OBJECTIVE: This
      work aimed to examine cortisol samples for usability, associations, and
      individual stability in neonates. SUBJECTS: The sample consisted of preterm
      infants (n=31). MATERIALS AND METHODS: Analyses on cortisol collected from cord
      blood and from saliva and urine samples on days 1, 7, and 14 included Spearman
      correlations and paired t-tests. RESULTS: Usability rates were 80.6% (cord
      blood), 85.9% (saliva), and 93.5% (urine). Salivary and urinary cortisol levels
      had significant correlation on day 1 only (p=0.004). Significant differences in
      individual stability of cortisol concentrations existed except in urine on days 1
      and 7 and in saliva on days 7 and 14. CONCLUSIONS: Usability was highest for
      urine samples. We found little correlation between cortisol sample levels at each
      time; individual stability of cortisol concentrations was minimal. Interpretation
      of cortisol findings in all studies should be performed cautiously.

PMID- 25389991
TI  - Evaluation of analgesic activity of levofloxacin in human experimental pain
      model.
AB  - BACKGROUND: Levofloxacin, an optically active isomer of ofloxacin, exerts broad
      spectrum antibacterial activity. Apart from its antibacterial action,
      experimental studies have documented antinociceptive properties in animal pain
      models suggesting an analgesic effect. This study was conducted with the aim to
      evaluate the analgesic activity of levofloxacin in healthy human volunteers.
      METHODS: This was an open label, prospective, non-randomized, interventional
      study conducted on 12 apparently healthy volunteers at a tertiary care teaching
      hospital in India. Permission from the Institutional Ethics Committee was
      obtained. After obtaining informed consent, volunteers fulfilling the inclusion
      criteria were enrolled. Analgesic activity was assessed by Cola cap and
      sphygmomanometer, a human experimental pain model. Observation of pain threshold
      and tolerance was recorded at baseline and at an interval of 2 h and 4 h after
      administration of levofloxacin (500 mg oral) in all 12 subjects. The results were
      analysed using repeated measures one way analysis of variance. RESULTS: The mean
      age of the volunteers was 27.5+/-3.26 years. A statistically significant increase
      in the pain threshold and tolerance was found at 2 h and 4 h when compared to
      baseline. CONCLUSIONS: Levofloxacin exhibited significant analgesic activity in a
      human pain model and can be used in infections associated with pain or for pre
      operative prophylaxis. Further investigations are required to understand the
      precise mechanism and pathway of antinociception exhibited by levofloxacin.

PMID- 25389992
TI  - Inflammatory caspases: key regulators of inflammation and cell death.
AB  - The innate immune system represents the first line of defence against infectious
      agents, and co-ordinates cellular and molecular mechanisms that result in
      effective inflammatory and anti-microbial responses against pathogens. Infection
      and cellular stress trigger assembly of canonical and noncanonical inflammasome
      complexes that activate the inflammatory caspases-1 and -11, respectively. These
      inflammatory caspases play key roles in innate immune responses by inducing
      pyroptosis to halt intracellular replication of pathogens, and by engaging the
      extracellular release of pro-inflammatory cytokines and danger signals. In
      addition, the inflammatory caspases-4, -5 and -11 were recently shown to directly
      bind microbial components. Although the immune roles of caspase-12 are debated,
      it was proposed to dampen inflammatory responses by interfering with caspase-1
      activation and other innate immune pathways. Here, we recapitulate the reported
      roles of inflammatory caspases with an emphasis on recent insights into their
      biological functions.

PMID- 25389993
TI  - The lymphocyte to monocyte ratio in peripheral blood represents a novel
      prognostic marker in patients with pancreatic cancer.
AB  - BACKGROUND: Intra-tumoral macrophages have been involved as important players in
      the pathogenesis and progression of cancer. Recently, inflammatory parameters of
      the systemic inflammatory response have also been proposed as usefully prognostic
      biomarkers. One of these, the lymphocyte to monocyte ratio (LMR) in peripheral
      blood has been shown as a prognostic factor in hematologic and some solid tumors.
      In this study we analyzed for the first time the prognostic value of LMR in a
      large middle European cohort of pancreatic cancer (PC) patients. METHODS: Data
      from 474 consecutive patients with ductal adenocarcinoma of the pancreas were
      evaluated retrospectively. Cancer-specific survival (CSS) was analyzed using the
      Kaplan-Meier method. To further evaluate the prognostic significance of the LMR,
      univariate and multivariate Cox regression models were calculated. RESULTS:
      Increased LMR at diagnosis was significantly associated with well-established
      prognostic factors, including high tumor stage and tumor grade (p<0.05). In
      univariate analysis, we observed that an increased LMR was a significant factor
      for better CSS in PC patients (HR 0.70; 95% CI 0.57-0.85; p<0.001). In
      multivariate analysis including age, Karnofsky Index, tumor grade, tumor stage,
      administration of chemotherapy, LMR and surgical resection, we confirmed
      increased LMR as an independent prognostic factor for CSS (HR 0.81; 95% CI 0.66
      0.99; p=0.04). CONCLUSIONS: In conclusion, we identified LMR as an independent
      prognostic factor in PC patients. Our results indicate that the LMR might
      represent a novel and useful marker for patient stratification in PC management.

PMID- 25389994
TI  - Automated immunoassays for the autoantibodies to carbamylated or citrullinated
      telopeptides of type I and II collagens.
AB  - BACKGROUND: The aim of the study was to describe automated immunoassays for
      autoantibodies to homocitrulline or citrulline containing telopeptides of type I
      and II collagen in various disease categories in an early arthritis series.
      METHODS: Serum samples were collected from 142 patients over 16 years of age with
      newly diagnosed inflammatory joint disease. All samples were analyzed with an
      automated inhibition chemiluminescence immunoassay (CLIA) using four different
      peptide pairs, each consisting of a biotinylated antigen and an inhibiting
      peptide. Assays were performed with an IDS-iSYS analyzer. Autoantibodies binding
      to homocitrulline and citrulline containing C-telopeptides of type I (HTELO-I,
      TELO-I) and type II collagens (HTELO-II, TELO-II) were analyzed. RESULTS: The
      mean ratio of HTELO-I inhibition in seropositive and seronegative rheumatoid
      arthritis (RA) was 3.07 (95% CI 1.41-11.60), p=0.003, and in seropositive and
      seronegative undifferentiated arthritis (UA) 4.90 (1.85-14.49), p<0.001. The
      respective mean ratios in seropositive and seronegative RA and UA were in TELO-I
      8.72 (3.68-58.01), p<0.001 and 3.13 (1.49-6.16), p=0.008, in HTELO-II 7.57 (3.18
      56.60), p<0.001 and 2.97 (1.23-6.69), p=0.037, and in TELO-II 3.01 (1.30-9.51),
      p=0.002 and 3.64 (1.86-7.65), p=0.008. In reactive arthritis, ankylosing
      spondylitis, psoriatic arthritis and unspecified spondyloarthritis the inhibition
      levels were similar to those observed in seronegative RA or UA. CONCLUSIONS:
      Autoantibodies binding to homocitrulline or citrulline containing telopeptides of
      type I and II collagen did not differ significantly. They were highest among
      patients with seropositive disease and they differentiated seropositive and
      seronegative arthritis.

PMID- 25389995
TI  - To avoid fasting time, more risk than benefits.

PMID- 25389996
TI  - Leptin, a mediator of cardiac damage associated with obesity.
AB  - Obesity and excess of adipose tissue are associated with the development of
      cardiovascular risk factors such as diabetes, hypertension, and hyperlipidemia.
      At the cardiac level, various morphological adaptations in cardiac structure and
      function occur in obese individuals. Different mechanisms linking obesity to
      these modifications have been postulated. Adipose tissue and epicardial fat
      releases a large number of cytokines and bioactive mediators such as leptin.
      Leptin circulates in proportion to body fat mass, thus serving as a satiety
      signal and informing central metabolic control centers as to the status of
      peripheral energy stores. It participates in numerous other functions both
      peripherally and centrally, as indicated by the wide distribution of leptin and
      the different isoforms of its receptor in different tissues including the heart.
      This hormone has distinct effects on the reproductive, cardiovascular, and immune
      systems; however, its role in the heart could mediate wide physiological effects
      observed in obese individuals. Oxidative stress is associated with obesity and
      may be considered to be a unifying mechanism in the development of obesity
      related comorbidities. It has been reported that obesity may induce systemic
      oxidative stress; in turn, oxidative stress is associated with an irregular
      production of adipokines. We herein review the current knowledge of cardiac
      effects of leptin and the possible mechanisms that are involved, including
      oxidative stress that plays a major role in the development of cardiovascular
      damage.

PMID- 25389997
TI  - Thyroid hormones and the heart.
AB  - Thyroid hormones have a significant impact on heart function, mediated by genomic
      and non-genomic effects. Consequently, thyroid hormones deficit as well as excess
      are expected to result in profound changes in cardiac function regulation and
      cardiovascular hemodynamics. Thyroid hormones upregulate the expression of the
      sarcoplasmic reticulum calcium-activated ATPase and downregulate the expression
      of phospholamban. Overall, hyperthyroidism is characterized by an increase in
      resting heart rate, blood volume, stroke volume, myocardial contractility, and
      ejection fraction. The development of "high-output heart failure" in
      hyperthyroidism may be due to "tachycardia-mediated cardiomyopathy." In contrast,
      in the hypothyroid state, thyroid hormone deficiency results in lower heart rate
      and weakening of myocardial contraction and relaxation, with prolonged systolic
      and early diastolic times. Cardiac preload is decreased owing to impaired
      diastolic function, cardiac afterload is increased, and chronotropic and
      inotropic functions are reduced. Subclinical thyroid dysfunction is relatively
      common in patients >65 years of age. In general, subclinical hypothyroidism
      increases the risk of cardiovascular heart disease (CHD) mortality and CHD
      events, but not of total mortality. The risk of CHD mortality and atrial
      fibrillation (but not other outcomes) in subclinical hyperthyroidism is higher
      among patients with very low levels of thyrotropin. Finally, medications such as
      amiodarone may induce hypothyroidism (mediated by the Wolff-Chaikoff effect) as
      well as hyperthyroidism (mediated by the Jod-Basedow effect). In both instances,
      the underlying cause is the high concentration of iodine in this medication. The
      purpose of this review is to assess the effects of thyroid hormones on the heart,
      and their clinical repercussions.

PMID- 25389998
TI  - Effects of hormones on platelet aggregation.
AB  - Platelets and their activation/inhibition mechanisms play a central role in
      haemostasis. It is well known agonists and antagonists of platelet activation;
      however, during the last years novel evidences of hormone effects on platelet
      activation have been reported. Platelet functionality may be modulated by the
      interaction between different hormones and their platelet receptors, contributing
      to sex differences in platelet function and even in platelet-mediated vascular
      damage. It has suggested aspects that apparently are well established should be
      reviewed. Hormones effects on platelet activity are included among them. This
      article tries to review knowledge about the involvement of hormones in platelet
      biology and activity.

PMID- 25389999
TI  - The role of leptin/adiponectin ratio in metabolic syndrome and diabetes.
AB  - The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with
      insulin resistance and adiposity as its central features. Identifying individuals
      with metabolic syndrome is important due to its association with an increased
      risk of coronary heart disease and type 2 diabetes mellitus. Attention has
      focused on the visceral adipose tissue production of cytokines (adipokines) in
      metabolic syndrome and type 2 diabetes mellitus, as the levels of the anti
      inflammatory adipokine adiponectin are decreased, while proinflammatory cytokines
      are elevated, creating a proinflammatory state associated with insulin resistance
      and endothelial dysfunction. In this review, we will give special attention to
      the role of the leptin/adiponectin ratio. We have previously demonstrated that in
      individuals with severe coronary artery disease, abdominal obesity was uniquely
      related to decreased plasma concentrations of adiponectin and increased leptin
      levels. Leptin/adiponectin imbalance was associated with increased waist
      circumference and a decreased vascular response to acetylcholine and increased
      vasoconstriction due to angiotensin II. Leptin and adiponectin have opposite
      effects on subclinical inflammation and insulin resistance. Leptin upregulates
      proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6;
      these are associated with insulin resistance and type 2 diabetes mellitus. In
      contrast, adiponectin has anti-inflammatory properties and downregulates the
      expression and release of a number of proinflammatory immune mediators.
      Therefore, it appears that interactions between angiotensin II and
      leptin/adiponectin imbalance may be important mediators of the elevated risk of
      developing type 2 diabetes mellitus and cardiovascular diseases associated with
      abdominal obesity.

PMID- 25390000
TI  - Circadian rhythm, sleep pattern, and metabolic consequences: an overview on
      cardiovascular risk factors.
AB  - Sleep duration is a risk factor for cardiovascular disease. Alteration in sleep
      pattern can induce the loss of circadian rhythmicity. Chronically, this
      desynchronization between endogenous rhythm and behavioral cycles can lead to an
      adverse metabolic profile, a proinflammatory condition and can increase the risk
      of cardiovascular disease. The circadian cycle can vary due to environmental
      cues. The circadian pacemaker is located in the suprachiasmatic nuclei; this
      central clock coordinates the circadian rhythm in the central nervous system and
      peripheral tissues. The mechanisms involved in sleep disturbance, circadian
      misalignment and adverse metabolic effects have yet to be fully elucidated. This
      review looks over the association among sleep alteration, circadian rhythm and
      the development of risk factors implicated in cardiovascular disease.

PMID- 25390001
TI  - The endocrine and cardiovascular systems: a close liaison.

PMID- 25390002
TI  - Relevance of SGK1 in structural, functional and molecular alterations produced by
      aldosterone in heart.
AB  - Aldosterone regulates sodium (Na+) and potassium (K+) transports in epithelial
      cells. Besides, aldosterone participates in cardiac alterations associated with
      hypertension, heart failure, diabetes, and other pathological alterations. One of
      the main cardiac alterations induced by aldosterone is cardiac hypertrophy in
      which different mechanisms are involved such as increased cardiomyocyte, calcium
      concentration, oxidative stress, and inflammatory and fibrotic mediators
      stimulation. Many epidemiological studies have demonstrated that left ventricular
      hypertrophy is associated with significantly increased risk of heart failure and
      malignant arrhythmias. SGK1 is a member of the serine/threonine kinase gene
      family that plays an important role in the absorption of Na+ and water through
      the Na+ channel in the apical membrane of tubular epithelial cells. SGK1 has been
      related to fibrotic mediator increase such as connective tissue growth factor
      (CTGF) and transforming growth factor-beta (TGF-beta) as well as inflammatory
      [tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta] and
      oxidative (NADPH oxidase) species. It has been shown that aldosterone induces
      SGK1 gene expression not only in kidneys but also in the heart. Supporting the
      central role of SGK1 in cardiac alterations induced by aldosterone, treatment
      with the mineralocorticoid antagonist spironolactone is able to reduce the gene
      expression of SGK1 in aldosterone-treated rats. Taken together, data suggest the
      involvement of SGK1 in a complex intracellular signaling, involving fibrotic,
      inflammatory, and oxidative pathways, which lead to cardiac hypertrophy and
      fibrosis induced by aldosterone.

PMID- 25390003
TI  - Mechanisms involved in developmental programming of hypertension and renal
      diseases. Gender differences.
AB  - BACKGROUND: A substantial body of epidemiological and experimental evidence
      suggests that a poor fetal and neonatal environment may "program" susceptibility
      in the offspring to later development of cardiovascular, renal and metabolic
      diseases. MATERIALS AND METHODS: This review focuses on current knowledge from
      the available literature regarding the mechanisms linking an adverse
      developmental environment with an increased risk for cardiovascular, renal and
      metabolic diseases in adult life. Moreover, this review highlights important sex
      dependent differences in the adaptation to developmental insults. RESULTS:
      Developmental programming of several diseases is secondary to changes in
      different mechanisms inducing important alterations in the normal development of
      several organs that lead to significant changes in birth weight. The different
      diseases occurring as a consequence of an adverse environment during development
      are secondary to morphological and functional cardiovascular and renal changes,
      to epigenetic changes and to an activation of several hormonal and regulatory
      systems, such as angiotensin II, sympathetic activity, nitric oxide, COX2-derived
      metabolites, oxidative stress and inflammation. The important sex-dependent
      differences in the developmental programming of diseases seem to be partly
      secondary to the effects of sex hormones. Recent studies have shown that the
      progression of these diseases is accelerated during aging in both sexes.
      CONCLUSIONS: The cardiovascular, renal and metabolic diseases during adult life
      that occur as a consequence of several insults during fetal and postnatal periods
      are secondary to multiple structural and functional changes. Future studies are
      needed in order to prevent the origin and reduce the incidence and consequences
      of developmental programmed diseases.

PMID- 25390004
TI  - Protective actions of melatonin and growth hormone on the aged cardiovascular
      system.
AB  - Epidemiological studies indicate that certain aspects of lifestyle and genetics
      act as risk factors for a variety of cardiovascular disorders, including coronary
      disease, hypertension, heart failure and stroke. Aging, however, appears to be
      the major contributor for morbidity and mortality of the impaired cardiovascular
      system. Growth hormone (GH) and melatonin seem to prevent cardiac aging, as they
      contribute to the recovery of several physiological parameters affected by age.
      These hormones exhibit antioxidant properties and decrease oxidative stress and
      apoptosis. This paper summarizes a set of studies related to the potential role
      that therapy with GH and melatonin may play in the protection of the altered
      cardiac function due to aging, with a focus on experiments performed in our
      laboratory using the senescence-accelerated mouse as an aging model. In general,
      we observed significantly increased inflammation, oxidative stress and apoptosis
      markers in hearts from senescence-accelerated prone 10-month-old animals compared
      to 2-month-old controls, while anti-inflammatory and antiapoptotic markers as
      well as endothelial nitric oxide synthase were decreased. Senescence-accelerated
      resistant animals showed no significant changes with age. GH or melatonin
      treatment prevented the age-dependent cardiac alterations observed in the
      senescence-accelerated prone group. Combined administration of GH plus melatonin
      reduced the age-related changes in senescence-accelerated prone hearts in an
      additive fashion that was different to that displayed when administered alone. GH
      and melatonin may be potential agents for counteracting oxidative stress,
      apoptosis and inflammation in the aging heart.

PMID- 25390005
TI  - Sex hormones in the cardiovascular system.
AB  - Gender-associated differences in the development of cardiovascular diseases have
      been described in humans and animals. These differences could explain the low
      incidence of cardiovascular disease in women in the reproductive period, such as
      stroke, hypertension, and atherosclerosis. The cardiovascular protection observed
      in females has been attributed to the beneficial effects of estrogen on
      endothelial function. Besides estrogen, sex hormones are able to modulate blood
      pressure by acting on important systems as cardiovascular, renal, and neural.
      They can have complementary or antagonistic actions. For example, testosterone
      can raise blood pressure by stimulating the renin-angiotensin-aldosterone system,
      whereas estrogen alone or combined with progesterone has been associated with
      decreased blood pressure. The effects of testosterone in the development of
      cardiovascular disease are contradictory. Although some researchers suggest a
      positive effect, others indicate negative actions of testosterone. Estrogens
      physiologically stimulate the release of endothelium-derived vasodilator factors
      and inhibit the renin-angiotensin system. Although the cardioprotective effects
      of estrogen are widely appreciated, little is known about the effects of
      progesterone, which is commonly used in hormone replacement therapy. Progesterone
      has both vasodilatory and vasoconstrictive effects in the vasculature, depending
      on the location of the vessel and the level of exposure. Nevertheless, the
      mechanisms through which sex hormones modulate blood pressure have not been fully
      elucidated. Therefore, the characterization of those could lead to a better
      understanding of hypertension in women and men and perhaps to improved forms of
      therapy.

PMID- 25390006
TI  - Reduced tubular proteinuria in hypertensive rats treated with losartan is
      associated with higher renal cortical megalin expression.
AB  - BACKGROUND: Several clinical studies have demonstrated that angiotensin II
      antagonists exert renoprotective effects beyond blood pressure control in
      hypertensive patients. The present work aimed to test the hypothesis that the
      antiproteinuric effects of losartan are associated with upregulation of the multi
      ligand endocytic receptors megalin and cubilin in the proximal tubule of
      spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: Fourteen-week-old
      SHRs were orally treated for 7 weeks with losartan (50 mg/kg, SHR-L), hydralazine
      (30 mg/kg, SHR-H), or vehicle (SHR-V). Blood pressure and renal function were
      determined prior to and following drug treatment. Expression of renal cortical
      proteins was determined by immunoblotting. RESULTS: Losartan and hydralazine
      reduced systolic blood pressure from pretreatment levels in SHRs to a similar
      extent. However, SHR-L displayed a much greater reduction in proteinuria than SHR
      H (44+/-3% vs. 15+/-1%, p<0.01) relative to pretreatment urinary protein
      excretion levels. In SHRs treated with vehicle, proteinuria increased from 87+/-5
      to 153+/-15 mg/(day kg BW). Reduced tubular proteinuria in SHRs treated with
      losartan was accompanied by a higher expression of megalin (125+/-28%) relative
      to either SHR-V or SHR-H. Neither losartan nor hydralazine significantly altered
      the renal cortical expression of cubilin in SHRs. CONCLUSION: Collectively, our
      data demonstrate that the additional renoprotective effects of angiotensin II
      blockade by losartan are associated with upregulation of megalin in the renal
      proximal tubule of SHRs. Moreover, it strengthens the view that tubular
      dysfunction may represent an important contributing mechanism underlying
      proteinuria in hypertension.

PMID- 25390007
TI  - Enhanced Na+, K+-ATPase activity and endothelial modulation decrease
      phenylephrine-induced contraction in aorta from ouabain-treated normotensive and
      hypertensive rats.
AB  - AIM: The purpose of this study was to compare the effect of long-term ouabain
      treatment on the vascular reactivity and Na+, K+-ATPase activity of a conductance
      artery from normotensive and hypertensive rats. METHODS: Male Wistar rats were
      treated with ouabain (~8.0 ug/day, subcutaneously) or vehicle for 5 and 20 weeks,
      and spontaneously hypertensive rats (SHRs) for 5 weeks. Vasoconstrictor response
      to phenylephrine (10-10 to 10-4 M) and relaxation curves to KCl (1-10 mM) were
      analyzed in thoracic aorta. The effects of endothelial removal, L-NAME (100 MUM),
      and indomethacin (10 MUM) were used to evaluate the endothelial, nitric oxide
      (NO), and cyclooxygenase (COX) modulation of phenylephrine response,
      respectively. Protein expression of endothelial and neuronal NO synthase (NOS)
      and COX-2 were also investigated. RESULTS: The phenylephrine-induced contraction
      was reduced, whereas the relaxation to KCl was enhanced in the aorta of ouabain
      treated Wistar rats and SHRs. In both strains, endothelial modulation of alpha
      adrenergic response was enhanced, related to an increased NO and reduced COX
      derived vasoconstrictor factor modulation. Aortas from 20-week ouabain-treated
      Wistar rats showed reduced COX-2 and enhanced eNOS protein expression. In SHRs, 5
      week ouabain treatment reduced COX-2 and increased nNOS protein expression.
      CONCLUSIONS: The results suggest that long-term ouabain treatment reduces the
      alpha-adrenergic response of aorta from normotensive rats and SHRs, associated
      with an increase of NO synthesis, reduced COX-2-derived vasoconstrictor factors,
      and enhanced ouabain-sensitive Na+, K+-ATPase activity. These aortic mechanisms
      could be adjustments to the elevated blood pressure induced by ouabain, even in
      the presence of preexisting hypertension.

PMID- 25390008
TI  - Comparison of steady state development and reduction of menopausal symptoms after
      oral or transdermal delivery of 17-beta-estradiol in young healthy symptomatic
      menopausal women.
AB  - OBJECTIVE: There is a renewed interest in the delivery of estradiol (E2) for the
      reduction of menopausal symptoms in young symptomatic menopausal women. This
      paper compares experimentally and theoretically obtained E2 plasma values by oral
      and transdermal delivery and compares them with relevant menopausal symptoms.
      STUDY DESIGN: Two independent previously published studies were compared, which
      each contained 42 young symptomatic menopausal women. Experimentally obtained
      plasma values at days 1, 7 and 21 were compared with a theoretical model, taken
      from the literature, for describing plasma values for an oral immediate release
      formulation, consecutively for 21 days. Menopausal symptoms were determined in
      the steady state for oral and transdermal delivery with the Kuppermann index,
      previously not reported. In the case of oral delivery, estradiol was compared
      with estradiol valerate. RESULTS: Previously published results for transdermal
      delivery of E2 showed that the matrix system establishes a steady state condition
      with the application of the first patch. Excellent agreement between
      theoretically predicted and experimentally obtained E2 plasma values for oral
      delivery in menopausal women was obtained. Circadian E2 plasma levels were
      observed continuously for transdermal delivery, were seen in oral delivery during
      first application and disappeared when steady state was achieved. Application of
      the prodrug E2-valerate delayed the maximum plasma peak from 1 pm to 4 pm,
      similar to the transdermal matrix patch. Investigating menopausal symptoms
      determined with the Kuppermann index did not reveal differences between oral or
      transdermal "E2 kinetic (hot flushes) relationship". This relationship was
      similar to symptomatic women suffering from hot flushes in untreated menopausal
      women or premenopausal women. Different menopausal symptoms required different E2
      plasma levels: the average E2 levels higher than 23 pg/mL in plasma did abolish
      insomnia in 50% of postmenopausal women, with 28 pg/mL is needed to suppress 50%
      of dysthymia; however, rather high levels of 41 pg/mL are needed to suppress 50%
      of hot flushes, suggesting a rather complex mechanism beyond an E2 receptor
      mediated process. CONCLUSION: There is a difference in the steady state between
      oral and transdermal E2 delivery. Steady state condition is achieved in the first
      application of a matrix patch, whereas with the application of a tablet the
      steady state is achieved in transdermal delivery within 12-14 days. Our reported
      calculated missed intake of a E2 tablet shows that E2 plasma levels drop for 4
      days consecutively. Our conducted study has several limitations: firstly, no
      cross-over was conducted, but a rather cumbersome mathematical modeling;
      secondly, healthy women with no accompanying severe diseases were included in
      this study. The higher the oral dose, the higher the E2 steady state levels, but
      the time to achieve steady state levels is independent from the E2 dose.

PMID- 25390009
TI  - Meditation can produce beneficial effects to prevent cardiovascular disease.
AB  - Coronary heart disease is the major cause of global cardiovascular mortality and
      morbidity. Lifestyle behaviour contributes as a risk factor: unhealthy diet,
      sedentary lifestyle, tobacco, alcohol, hypertension, diabetes, dyslipidemia and
      psychosocial stress. Atherosclerosis pathologic mechanisms involving oxidative
      stress, dyslipidemia, inflammation and senescence are associated with arterial
      wall damage and plaque formation. Stress reduction was observed in several types
      of meditation. After meditation, hormonal orchestration modulates effects in the
      central nervous system and in the body. All types of meditation are associated
      with blood pressure control, enhancement in insulin resistance, reduction of
      lipid peroxidation and cellular senescence, independent of type of meditation.
      This review presents scientific evidence to explain how meditation can produce
      beneficial effects on the cardiovascular system, and particularly regarding
      vascular aspects.

PMID- 25390010
TI  - Per3 length polymorphism in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: A number of observations support the involvement of circadian clock
      genes in the regulation of metabolic processes. One of these circadian genes,
      Per3, exhibits a variable number tandem repeat length polymorphism, consisting of
      two alleles, namely four and five repeat alleles, in its exon 18. The objective
      of this study was to examine the existence of Per3 variants in patients with type
      2 diabetes mellitus (T2DM) as compared to a non T2DM control group. METHODS:
      Intravenous blood samples were collected to obtain white blood cells from 302
      T2DM patients and 330 non-diabetic, age- and sex-matched, individuals. Per3
      genotyping was performed on DNA by polymerase chain reaction. RESULTS: Frequency
      of five repeat allele was higher, and that of four repeat allele lower, in T2DM
      patients as compared to non-diabetic controls (chi2=6.977, p=0.0082) CONCLUSIONS:
      The results indicate an association of Per3 five repeat allele with T2DM
      occurrence and suggest that individuals with five repeat allele may be at a
      greater risk for T2DM as compared to those carrying the four repeat allele.

PMID- 25390011
TI  - Pathophysiology of adipose tissue: effects of steroid hormones--part D.

PMID- 25390012
TI  - Brown adipose tissue, thermogenesis, angiogenesis: pathophysiological aspects.
AB  - The number of obese and overweight individuals is globally rising, and obesity
      associated disorders such as type 2 diabetes, cardiovascular disease and certain
      types of cancer are among the most common causes of death. While white adipose
      tissue is the key player in the storage of energy, active brown adipose tissue
      expends energy due to its thermogenic capacity. Expanding and activating brown
      adipose tissue using pharmacological approaches therefore might offer an
      attractive possibility for therapeutic intervention to counteract obesity and its
      consequences for metabolic health.

PMID- 25390013
TI  - The influence of sex steroids on adipose tissue growth and function.
AB  - Obesity remains a major global health concern. Understanding the metabolic
      influences of the obesity epidemic in the human population on maintenance of a
      healthy weight and metabolic profile is still of great significance. The
      importance and role of white adipose tissue has been long established,
      particularly with excess adiposity. Brown adipose tissue (BAT), however, has only
      recently been shown to contribute significantly to the metabolic signature of
      mammals outside the previously recognised role in small mammals and neonates.
      BAT's detection in adults has led to a renewed interest and is now considered to
      be a potential therapeutic target to prevent excess white fat accumulation in
      obesity, a theory further promoted by the recent discovery of beige fat. Adipose
      tissue distribution varies significantly between genders. Pre-menopausal females
      often show enhanced lower and peripheral fat deposition in adiposity deposition
      compared to the male profile of central and visceral fat accumulation with
      obesity. This sex disparity is partly attributed to the different effects of sex
      hormone profiles and interactions on the adipose tissue system. In this review,
      we explore this intricate relationship and show how modifications in the effects
      of sex hormones impact on both brown and white adipose tissues. We also discuss
      the impact of sex hormones on activation of the hypothalamic-pituitary-adrenal
      (HPA) axis and how the three pathways between adiposity, HPA and sex steroids can
      have a major contribution to the prevention or maintenance of obesity and
      therefore on overall health.

PMID- 25390014
TI  - Brown adipose tissue and thermogenesis.
AB  - The growing understanding of adipose tissue as an important endocrine organ with
      multiple metabolic functions has directed the attention to the (patho)physiology
      of distinct fat depots. Brown adipose tissue (BAT), in contrast to bona fide
      white fat, can dissipate significant amounts of chemical energy through uncoupled
      respiration and heat production (thermogenesis). This process is mediated by the
      major thermogenic factor uncoupling protein-1 and can be activated by certain
      stimuli, such as cold exposure, adrenergic compounds or genetic alterations.
      White adipose tissue (WAT) depots, however, also possess the capacity to acquire
      brown fat characteristics in response to thermogenic stimuli. The induction of a
      BAT-like cellular and molecular program in WAT has recently been termed
      "browning" or "beiging". Promotion of BAT activity or the browning of WAT is
      associated with in vivo cold tolerance, increased energy expenditure, and
      protection against obesity and type 2 diabetes. These preclinical observations
      have gained additional significance with the recent discovery that active BAT is
      present in adult humans and can be detected by 18fluor-deoxy-glucose positron
      emission tomography coupled with computed tomography. As in rodents, human BAT
      can be activated by cold exposure and is associated with increased energy
      turnover and lower body fat mass. Despite the tremendous progress in brown fat
      research in recent years, pharmacological concepts to harness BAT function
      therapeutically are currently still lacking.

PMID- 25390016
TI  - The pathophysiology of abdominal adipose tissue depots in health and disease.
AB  - Obesity is currently the most important contributor to ill health and expenditure
      worldwide. More alarming is the fact that the pediatric population parallels
      adults, with obesity closely associated to type 2 diabetes mellitus (T2D),
      cardiovascular disease, hypertension, non-alcoholic fatty liver disease, vitamin
      D deficiency (VDD) and certain types of cancer. The observation in the early
      1950s that android or truncal adipose tissue (AT) distribution compared to gynoid
      had a greater association with metabolic dysfunction, in particular T2D and
      cardiovascular disease risk, led to the hypothesis that obesity-associated
      complications are not associated with fat mass per se, but the pattern of fat
      distribution. This concept was further supported by groups of individuals with
      metabolic dysfunction despite a lean phenotype, and healthy obese people
      protected from metabolic dysfunction. It is now well recognized that an increase
      in visceral AT is an independent risk factor for the development of obesity
      associated comorbidities with AT depot distribution, their anatomic, cellular and
      molecular features defining their role. The differences and the plasticity of
      subcutaneous, visceral and ectopic ATs to store and release fatty acids and to
      synthesize and secrete adipokines, defines the metabolic outcomes. The present
      review will examine the phenotypic and pathophysiological differences between the
      different AT depots, with a particular focus on the abdominal depots and their
      link to metabolic complications.

PMID- 25390017
TI  - Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity
      associated insulin resistance and cardiovascular risk.
AB  - Obesity leads to the development of type 2 diabetes mellitus, which is a strong
      risk factor for cardiovascular disease. A better understanding of the molecular
      basis of obesity will lead to the establishment of effective prevention
      strategies for cardiovascular diseases. Adipocytes have been shown to generate a
      variety of endocrine factors termed adipokines/adipocytokines. Obesity-associated
      changes to these adipocytokines contribute to the development of cardiovascular
      diseases. Adiponectin, which is one of the most well-characterized
      adipocytokines, is produced exclusively by adipocytes and exerts insulin
      sensitizing and anti-atherogenic effects. Obese subjects have lower levels of
      circulating adiponectin, and this is recognized as one of the factors involved in
      obesity-induced insulin resistance and atherosclerosis. Another
      pathophysiological feature of obesity may involve the low-grade chronic
      inflammation in adipose tissue. This inflammatory process increases oxidative
      stress in adipose tissue, which may affect remote organs, leading to the
      development of diabetes, hypertension, and atherosclerosis. Nuclear hormone
      receptors (NRs) regulate the transcription of the target genes in response to
      binding with their ligands, which include metabolic and nutritional substrates.
      Among the various NRs, peroxisome proliferator-activated receptor gamma promotes
      the transcription of adiponectin and antioxidative enzymes, whereas
      mineralocorticoid receptor mediates the effects of aldosterone and glucocorticoid
      to induce oxidative stress in adipocytes. It is hypothesized that both play
      crucial roles in the pathophysiology of obesity-associated insulin resistance and
      cardiovascular diseases. Thus, reduced adiponectin and increased oxidative stress
      play pathological roles in obesity-associated insulin resistance to increase the
      cardiovascular disease risk, and various NRs may be involved in this
      pathogenesis.

PMID- 25390018
TI  - Crosstalk between adipose tissue and blood vessels in cardiometabolic syndrome:
      implication of steroid hormone receptors (MR/GR).
AB  - Crosstalk between adipose tissue and blood vessels is vital to vascular
      homeostasis and is disturbed in cardiovascular and metabolic diseases such as
      hypertension, diabetes and obesity. Cardiometabolic syndrome (CMS) refers to the
      clustering of obesity-related metabolic disorders such as insulin resistance,
      glucose and lipid profile alterations, hypertension and cardiovascular diseases.
      Mechanisms underlying these associations remain unclear. Adipose tissue
      associated with the vasculature [known as perivascular adipose tissue (PVAT)] has
      been shown to produce myriads of adipose tissue-derived substances called
      adipokines, including hormones, cytokines and reactive oxygen species (ROS),
      which actively participate in the regulation of vascular function and local
      inflammation by endocrine and/or paracrine mechanisms. As a result, the signaling
      from PVAT to the vasculature is emerging as a potential therapeutic target for
      obesity and diabetes-related vascular dysfunction. Accumulating evidence supports
      a shift in our understanding of the crucial role of elevated plasma levels of
      aldosterone in obesity, promoting insulin resistance and hypertension. In
      obesity, aldosterone/mineralocorticoid receptor (MR) signaling induces an
      abnormal secretion of adipokines, ROS production and systemic inflammation, which
      in turn contribute to impaired insulin signaling, reduced endothelial-mediated
      vasorelaxation, and associated cardiovascular abnormalities. Thus, aldosterone
      excess exerts detrimental metabolic and vascular effects that participate to the
      development of the CMS and its associated cardiovascular abnormalities. In this
      review, we focus on the physiopathological roles of corticosteroid receptors in
      the interplay between PVAT and the vasculature, which underlies their potential
      as key regulators of vascular function.

PMID- 25390015
TI  - Enzymatic intracrine regulation of white adipose tissue.
AB  - Abdominal fat formation has become a permanent risk factor for metabolic syndrome
      and various cancers in one-third of the world's population of obese and even lean
      patients. Formation of abdominal fat involves additional mechanisms beyond an
      imbalance in energy intake and expenditure, which explains systemic obesity. In
      this review, we briefly summarized autonomous regulatory circuits that locally
      produce hormones from inactive precursors or nutrients for intra-/auto-/paracrine
      signaling in white adipose depots. Enzymatic pathways activating steroid and
      thyroid hormones in adipose depots were compared with enzymatic production of
      retinoic acid from vitamin A. We discussed the role of intracrine circuits in fat
      depot functions and strategies to reduce abdominal adiposity through thermogenic
      adipocytes with interrupted generation of retinoic acid.

PMID- 25390019
TI  - Interaction of circadian and stress systems in the regulation of adipose
      physiology.
AB  - Endogenous circadian clocks facilitate the adaptation of physiology and behavior
      to recurring environmental changes brought about by the Earth's rotation around
      its axis. Adipose tissues harbor intrinsic circadian oscillators based on
      interlocked transcriptional-translational feedback loops built from a set of
      clock genes that regulate important aspects of lipid metabolism and adipose
      endocrine function. These adipocyte clocks are reset via neuronal and endocrine
      pathways originating from a master circadian pacemaker residing in the
      hypothalamic suprachiasmatic nucleus. One important mediator of circadian output
      is the stress hormone cortisol, which, at the same time, is one of the major
      regulators of adipose physiology. In this review we summarize recent findings on
      the interaction between circadian and stress systems in the regulation of adipose
      physiology and discuss the implications of this crosstalk for the development of
      metabolic disorders associated with circadian disruption and/or chronic stress,
      for example in shift workers.

PMID- 25390020
TI  - Glucocorticoid hormones and energy homeostasis.
AB  - Glucocorticoids (GC) and their cognate intracellular receptor, the glucocorticoid
      receptor (GR), have been characterised as critical checkpoints in the endocrine
      control of energy homeostasis in mammals. Indeed, aberrant GC action has been
      linked to a variety of severe metabolic diseases, including obesity, insulin
      resistance and type 2 diabetes. As a steroid-binding member of the nuclear
      receptor superfamily of transcription factors, the GR translocates into the cell
      nucleus upon GC binding where it serves as a transcriptional regulator of
      distinct GC-responsive target genes that are - in many cases - associated with
      glucose and lipid regulatory pathways and thereby intricately control both
      physiological and pathophysiological systemic energy homeostasis. Here, we
      summarize the current knowledge of GC/GR function in energy metabolism and
      systemic metabolic dysfunction, particularly focusing on glucose and lipid
      metabolism.

PMID- 25390021
TI  - Nuclear hormone receptors PXR and CAR and metabolic diseases.
AB  - Nuclear receptors (NRs) belong to a superfamily of evolutionarily related DNA
      binding transcription factors that can be activated by steroid and thyroid
      hormones, and other lipid metabolites. Ligand activated NRs can regulate target
      gene expression by binding to DNA response elements present in the target gene
      promoters. Through this regulation, NRs are broadly implicated in physiology and
      metabolism. In this chapter, we will focus on the xenobiotic receptors and their
      recently discovered functions in metabolic diseases.

PMID- 25390023
TI  - Race differences in obesity and its relationship to the sex hormone milieu.
AB  - A sexual dimorphism exists in which increased abdominal and visceral adipose
      tissue (VAT) - found in women and marked by low sex hormone binding globulin
      (SHBG) and high bioavailable testosterone (BT) - is related to the metabolic risk
      profile. In men, increased BT is related to decreased abdominal obesity and a
      decrease in the metabolic risk profile. In women, race differences have been
      found in androgenic sex steroids including SHBG and BT as well as central fat
      distribution, creating inherently greater metabolic risk for certain populations.
      Estrogen and estrogen receptor isoforms play a role in fat deposition and
      distribution and may influence the changes that occur during the menopausal
      transition. Androgenic sex steroids serve a mediating role, influencing VAT
      accumulation and its associated metabolic risk factors while VAT also serves a
      mediating role influencing the androgenic sex steroid-metabolic risk relationship
      in women. Furthermore, androgenic sex steroids and VAT may independently
      contribute to the variance in several metabolic variables associated with
      cardiovascular disease, type 2 diabetes, and their antecedent conditions such as
      the metabolic syndrome. Race has been shown to modify the relationship between
      androgenic sex steroids and metabolic variables associated with risk for diabetes
      in Black and White women. Further research is warranted to examine the mechanisms
      involved in race differences. Total adiposity and central fat distribution in
      accordance with changes in the hormone and metabolic milieu influence breast
      cancer risk, which varies by race and menopausal status. These findings have
      broader implications for the study of health promotion/disease prevention in
      women.

PMID- 25390022
TI  - Role of the adipocyte-derived hormone leptin in reproductive control.
AB  - Achievement of sexual maturation and maintenance of fertility in adulthood are
      functions that are sensitive to the metabolic status of the organism,
      particularly the magnitude of fat reserves. In this sense, the adipocyte-derived
      hormone, leptin, plays a major role in linking metabolic cues and the control of
      multiple neuroendocrine axes. The hypothalamus is a key site mediating leptin
      actions, including those involved in the modulation of the hypothalamus-pituitary
      gonads (HPG) axis at different stages of development and in different
      environmental conditions. In the present review, we provide an update of the role
      of leptin in reproduction and discuss its interactions with neurons,
      neurotransmitters and downstream targets of the reproductive axis, with a special
      emphasis on the actions of leptin in the central nervous system. We hope this
      review will contribute to the understanding of the mechanisms whereby metabolic
      signals, especially leptin, influence the reproductive neuroendocrine axis
      modulating its activity in different nutritional states. Special attention will
      be given to recent advances in the identification of key hypothalamic sites and
      signaling pathways relevant to leptin's action in reproductive control.

PMID- 25390024
TI  - Neuroendocrine control of satiation.
AB  - Abstract Eating is a simple behavior with complex functions. The unconscious
      neuroendocrine process that stops eating and brings a meal to its end is called
      satiation. Energy homeostasis is mediated accomplished through the control of
      meal size via satiation. It involves neural integrations of phasic negative
      feedback signals related to ingested food and tonic signals, such as those
      related to adipose tissue mass. Energy homeostasis is accomplished through
      adjustments in meal size brought about by changes in these satiation signals. The
      best understood meal-derived satiation signals arise from gastrointestinal
      nutrient sensing. Gastrointestinal hormones secreted during the meal, including
      cholecystokinin, glucagon-like peptide 1, and PYY, mediate most of these. Other
      physiological signals arise from activation of metabolic-sensing neurons, mainly
      in the hypothalamus and caudal brainstem. We review both classes of satiation
      signal and their integration in the brain, including their processing by
      melanocortin, neuropeptide Y/agouti-related peptide, serotonin, noradrenaline,
      and oxytocin neurons. Our review is not comprehensive; rather, we discuss only
      what we consider the best-understood mechanisms of satiation, with a special
      focus on normally operating physiological mechanisms. 

PMID- 25390025
TI  - Male infertility: biomolecular aspects.
AB  - Male infertility is a problem that faces increasing interest, and the continuous
      development of assisted reproduction techniques solicits attempts to identify a
      precise diagnosis, in particular for idiopathic infertile couples and those
      undergoing assisted reproductive technique cycles. To date, diagnosis of male
      infertility is commonly based on standard semen analysis, but in many cases, this
      is not enough to detect any sperm abnormality. A better understanding of
      biomolecular issues and mechanism of damaged spermatogenesis and the refinement
      of the molecular techniques for sperm evaluation and selection are important
      advances that can lead to the optimization of diagnostic and therapeutic
      management of male and couple infertility. Faced with a growing number of new
      proposed techniques and diagnostic tests, it is fundamental to know which tests
      are already routinely used in the clinical practice and those that are likely to
      be used in the near future. This review focuses on the main molecular diagnostic
      techniques for male infertility and on newly developed methods that will probably
      be part of routine sperm analysis in the near future.

PMID- 25390026
TI  - Approaches to study in undergraduate nursing students in regional Victoria,
      Australia.
AB  - In developmental research to devise a strategy to identify students who may
      benefit from assistance with learning habits, approaches to study were explored
      in undergraduate nursing students (n=122) enrolled in a compulsory first-year
      course in physiology at a regional Australian university. The course constituted
      30 credits (25%) of their first year of study. Using the Approaches and Study
      Skills Inventory (ASSIST), students were identified as adopting a deep (n = 38,
      31%), strategic (n = 30, 25%), or a surface (n = 54, 44%) approach to study.
      Internal consistency (Cronbach's alpha [alpha]) for deep, strategic, and surface
      was 0.85, 0.87, and 0.76, respectively. Subsequently, a cluster analysis was done
      to identify two groupings: a "surface" group (n = 53) and a "deep/strategic"
      group (n = 69). The surface group scored lower in deep (33.28 +/- 6.42) and
      strategic (39.36 +/- 6.79) approaches and higher in the surface (46.96 +/- 9.57)
      approach. Conversely, the deep/strategic group scored 46.10 +/- 6.81, 57.17 +/-
      7.81, and 41.87 +/- 6.47 in deep, strategic, and surface styles, respectively.
      This application of the ASSIST questionnaire and cluster analysis thus
      differentiated students adopting a surface approach to study. This strategy may
      enable educators to target resources, for example additional tutorial
      opportunities, peer-assisted study support, and tutor-led seminar sessions aimed
      at encouraging students to adopt a less superficial approach to study.

PMID- 25390027
TI  - Toxicological evaluation of the aqueous extract of Acalypha wilkesiana in Wistar
      albino rats.
AB  - BACKGROUND: Acalypha wilkesiana (Euphorbiaceae) is highly accepted for
      traditional treatment of human plasmodiasis in Africa. METHODS: The toxicological
      effects of the aqueous leaf extract of A. wilkesiana were studied in 45 male and
      female Wistar albino rats. An acute toxicity testing was done using 21 rats
      divided into seven groups and LD50 determined. In the sub-chronic toxicity study,
      the extract was administered orally over a period of 28 days to rats in three
      groups with doses of 400 mg kg-1, 800 mg kg-1 and 1,600 mg kg-1, respectively,
      and the fourth group administered with water served as control. Blood samples
      were collected for hematological and serum biochemical analysis; organs of the
      animals were harvested for histopathological examination. RESULTS: The acute
      toxicity testing showed that the extract was non-toxic at doses up to 3,000 mg kg
      1 and the LD50 was calculated to be 2,828.34 mg kg-1. The study showed that at
      1,600 mg kg-1 dose, the extract caused a decrease in the level of neutrophils
      (NEUT) while lymphocytes (LYMP) were statistically significantly increased. The
      administration of the extract also resulted in varying significant dose dependent
      increase in the levels of aspartate amino transferase (AST), alanine
      aminotransferase (ALT) and alkaline phosphatase (ALP). There were also
      significant increases in the level of total protein (TP), urea (URN) and albumin
      (GLB) especially at 1,600 mg kg-1 dosage. Histopathology showed that the extract
      caused mild to severe significant lesions that are dose dependent in the liver
      and kidney when compared with the control group. CONCLUSIONS: Prolonged
      administration of high dose of A. wilkesiana extract has tendency to cause organ
      toxicity.

PMID- 25390028
TI  - Endothelium nitric oxide-independent vasorelaxant effects of the aqueous extract
      from Stephania abyssinica on the isolated rat thoracic aorta.
AB  - BACKGROUND: Stephania abyssinica (Dillon & A. Rich) Walp (Menispermaceae) is a
      medicinal plant used in the west region of Cameroon to treat arterial
      hypertension. The present study evaluated the vasorelaxant effects of the aqueous
      (AESA) and methanol (MESA) extracts from the fresh leaves of S. abyssinica on
      aorta rings isolated from Wistar rats. METHODS: Aorta rings with intact
      endothelium were contracted with KCl (60 mM) or phenylephrine (10-5 M) and
      exposed to cumulative concentrations of each extract, ranging from 10 to 1,000
      ug/mL. The vasorelaxant effects of AESA were further evaluated in presence of
      Nomega-nitro-L-arginine methyl ester (L-NAME, 10-4 M), tetraethylammonium (TEA, 5
      uM), glibenclamide (5 uM), propranolol (5 uM), and the association glibenclamide
      propranolol (AGP). In another set of experiments, the effect of AESA was
      evaluated on calcium-induced contraction in a hyperpotassic milieu. RESULTS: AESA
      and MESA exhibited a concentration-dependent vasorelaxation on KCl-contracted
      aortic rings with respective EC50 of 160.10 and 346.50 ug/mL. AESA similarly
      relaxed aortic rings contracted with phenylephrine (EC50, 176.80 ug/mL). The
      vasorelaxant activity of AESA was not significantly affected by L-NAME but was
      markedly reduced by TEA, glibenclamide, propranolol, and AGP. AESA strongly
      inhibited the Ca2+-induced contraction by 95%. CONCLUSIONS: These results support
      the use of S. abyssinica against arterial hypertension and suggest that the
      vasorelaxant effect of AESA is not mediated via the endothelium/nitric oxide
      pathway. AESA relaxant properties might be due to an inhibition of Ca2+ influx
      and/or the activation of ATP-sensitive K+ channels probably via the stimulation
      of beta-adrenergic receptors.

PMID- 25390029
TI  - The miaoyao fanggan sachets regulate humoral immunity and cellular immunity in
      mice.
AB  - BACKGROUND: Although some studies in the southeast part of Guizhou Province have
      suggested that Miaoyao Fanggan sachets (MFS) prevent influenza, little is known
      about its influence on immune systems. Influenza virus mainly infects immune
      compromised individuals. The effects of MFS have mainly been recognized in
      clinical practice. However, there have been relatively few studies on its
      biological mechanism. Here we investigated whether MFS was able to affect the
      mucosal immunization and the activation of alveolar macrophages (AM), CD4+and
      CD8+ T-cells in vivo. METHODS: Eighty Kunming male mice were treated with MFS
      continuously or intermittently with Yu-Ping-Feng powder (YPF-P) (positive control
      group) or with normal saline (NS) (control group) for 4 weeks, respectively. Mice
      treated with MFS were further divided into the continuous inhalation group (12 h
      daily/4 weeks) and the discontinuous inhalation group (1 h, three times a day for
      4 weeks). Mice in both groups were placed under 0.5 m3 masks which had four
      ventilation holes (10*15 cm) containing 40 g MFS. Positive control mice were
      orally treated with YPF-P 0.2 mg/10 g/day once a day for 4 weeks. Control mice
      were orally treated with equal volumes of NS once a day for 4 weeks. MFS was
      replaced every 6 days. Administration of YPF-P was used as a positive control
      since it has been used as an established Traditional Chinese Medicine (TCM)
      treatment before. After 4 weeks, mice in all experimental groups were sacrificed.
      IgA and IgG1 in lung and blood serum were detected by Western blot and enzyme
      linked immuno sorbent assay (ELISA). The expression of alveolar macrophages (AM)
      in mice was analyzed by immunochemistry test based on CD68+staining. Blood
      samples were collected in which CD4+and CD8+T-cells were analyzed by flow
      cytometry. RESULTS: Mice continuously and intermittently inhaling MFS showed a
      moderate increase in IgA and IgG1 protein levels compared with mice in the
      control groups. There was also a slightly significant increase in the number of
      AM in the continuous inhalation group compared with mice in the control groups
      (p<0.05). Furthermore, compared with controls, there was also a slightly
      significant increase in the number and percentage of CD4+and CD8+T-cells in both
      the continuous inhalation group and the discontinuous inhalation group (p<0.05).
      CONCLUSIONS: MFS was able to up-regulate the protein levels of sIgA and IgG1.
      Meanwhile, MFS could activate AM, CD4+and CD8+T-cells in mice. Our data have, for
      the first time, demonstrated that the protection against influenza by MFS is
      partly through activation of the innate and adaptive cell-mediated immune
      responses, indicating MFS as a potential new immune-modulatory agent for
      respiratory tract infectious disease.

PMID- 25390030
TI  - Sensitivity analysis of methods for active surveillance of acute myocardial
      infarction using electronic databases.
AB  - BACKGROUND: The validity of conclusions from observational studies depends on
      decisions regarding design, analysis, data quality, and implementation. Through
      sensitivity analyses, we explored the impact of such decisions on balance control
      and risk estimates. METHODS: Using as a template the Mini-Sentinel protocol for
      the active surveillance of acute myocardial infarction (MI) in association with
      use of antidiabetic agents, we defined cohorts of new users of metformin and
      second-generation sulfonylureas, baseline covariates and acute MI events using
      three combinations of washout and baseline periods. Using propensity-score
      matching, we assessed balance control and risk estimates using cumulative data
      for matching all patients compared with not rematching prior matches in quarterly
      analyses over the follow-up period. RESULTS: A longer washout period increased
      the confidence in new-user status, but at the expense of sample size; a longer
      baseline period improved capture of covariates related to pre-existing chronic
      conditions. When all patients were matched each quarter, balance was improved and
      risk estimates were more robust, especially in the later quarters. CONCLUSIONS:
      Durations of washout and baseline periods influence the likelihood of new-user
      status and sample size. Matching all patients tends to result in better covariate
      balance than matching only new patients. Decisions regarding the durations of
      washout and baseline periods depend on the specific research question and
      availability of longitudinal patient data within the database. This paper
      demonstrates the importance and utility of sensitivity analysis of methods for
      evaluating the robustness of results in observational studies.

PMID- 25390031
TI  - Should the history of epidemiology be taught in epidemiology training programs?
AB  - BACKGROUND: Currently, there is no evidence concerning the presence of historical
      content in the epidemiology curricula of the United States and abroad. Similarly,
      it is not known how epidemiologists view this topic in the context of master's or
      doctoral level course work. METHODS: We attempted to fill these knowledge gaps
      with data from 2 online surveys-Survey I administered to persons in charge of all
      epidemiology training programs in North America and Survey II to epidemiologists
      practicing around the world. RESULTS: A substantial minority (39%) of graduate
      programs in epidemiology in the United States teach a course on the history of
      the field. In both surveys, the most common reasons selected for teaching such a
      course were "To build a sense of identity as an epidemiologist" and "As a tool
      for achieving a deeper understanding into specific methods and concepts."
      CONCLUSION: The majority of respondents, from 63 countries, agreed that the
      history of epidemiology should be included in curricula for graduate students in
      epidemiology.

PMID- 25390032
TI  - Higher vulnerability and stress sensitivity of neuronal precursor cells carrying
      an alpha-synuclein gene triplication.
AB  - Parkinson disease (PD) is a multi-factorial neurodegenerative disorder with loss
      of dopaminergic neurons in the substantia nigra and characteristic intracellular
      inclusions, called Lewy bodies. Genetic predisposition, such as point mutations
      and copy number variants of the SNCA gene locus can cause very similar PD-like
      neurodegeneration. The impact of altered alpha-synuclein protein expression on
      integrity and developmental potential of neuronal stem cells is largely
      unexplored, but may have wide ranging implications for PD manifestation and
      disease progression. Here, we investigated if induced pluripotent stem cell
      derived neuronal precursor cells (NPCs) from a patient with Parkinson's disease
      carrying a genomic triplication of the SNCA gene (SNCA-Tri). Our goal was to
      determine if these cells these neuronal precursor cells already display
      pathological changes and impaired cellular function that would likely predispose
      them when differentiated to neurodegeneration. To achieve this aim, we assessed
      viability and cellular physiology in human SNCA-Tri NPCs both under normal and
      environmentally stressed conditions to model in vitro gene-environment
      interactions which may play a role in the initiation and progression of PD. Human
      SNCA-Tri NPCs displayed overall normal cellular and mitochondrial morphology, but
      showed substantial changes in growth, viability, cellular energy metabolism and
      stress resistance especially when challenged by starvation or toxicant challenge.
      Knockdown of alpha-synuclein in the SNCA-Tri NPCs by stably expressed short
      hairpin RNA (shRNA) resulted in reversal of the observed phenotypic changes.
      These data show for the first time that genetic alterations such as the SNCA gene
      triplication set the stage for decreased developmental fitness, accelerated
      aging, and increased neuronal cell loss. The observation of this "stem cell
      pathology" could have a great impact on both quality and quantity of neuronal
      networks and could provide a powerful new tool for development of neuroprotective
      strategies for PD. 

PMID- 25390033
TI  - Dendritic Na+ spikes enable cortical input to drive action potential output from
      hippocampal CA2 pyramidal neurons.
AB  - Synaptic inputs from different brain areas are often targeted to distinct regions
      of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large
      somatic EPSPs that efficiently trigger action potential (AP) output, whereas
      inputs to distal dendrites are greatly attenuated and may largely modulate AP
      output. In contrast to most other cortical and hippocampal neurons, hippocampal
      CA2 pyramidal neurons show unusually strong excitation by their distal dendritic
      inputs from entorhinal cortex (EC). In this study, we demonstrate that the
      ability of these EC inputs to drive CA2 AP output requires the firing of local
      dendritic Na+ spikes. Furthermore, we find that CA2 dendritic geometry
      contributes to the efficient coupling of dendritic Na+ spikes to AP output. These
      results provide a striking example of how dendritic spikes enable direct cortical
      inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output
      and thereby enable efficient cortico-hippocampal information flow.

PMID- 25390034
TI  - Adolescent sleep patterns and night-time technology use: results of the
      Australian Broadcasting Corporation's Big Sleep Survey.
AB  - INTRODUCTION: Electronic devices in the bedroom are broadly linked with poor
      sleep in adolescents. This study investigated whether there is a dose-response
      relationship between use of electronic devices (computers, cellphones,
      televisions and radios) in bed prior to sleep and adolescent sleep patterns.
      METHODS: Adolescents aged 11-17 yrs (n = 1,184; 67.6% female) completed an
      Australia-wide internet survey that examined sleep patterns, sleepiness, sleep
      disorders, the presence of electronic devices in the bedroom and frequency of use
      in bed at night. RESULTS: Over 70% of adolescents reported 2 or more electronic
      devices in their bedroom at night. Use of devices in bed a few nights per week or
      more was 46.8% cellphone, 38.5% computer, 23.2% TV, and 15.8% radio. Device use
      had dose-dependent associations with later sleep onset on weekdays (highest-dose
      computer adjOR  = 3.75: 99% CI  = 2.17-6.46; cellphone 2.29: 1.22-4.30) and
      weekends (computer 3.68: 2.14-6.32; cellphone 3.24: 1.70-6.19; TV 2.32: 1.30
      4.14), and later waking on weekdays (computer 2.08: 1.25-3.44; TV 2.31: 1.33
      4.02) and weekends (computer 1.99: 1.21-3.26; cellphone 2.33: 1.33-4.08; TV 2.04:
      1.18-3.55). Only 'almost every night' computer use (: 2.43: 1.45-4.08) was
      associated with short weekday sleep duration, and only 'almost every night'
      cellphone use (2.23: 1.26-3.94) was associated with wake lag (waking later on
      weekends). CONCLUSIONS: Use of computers, cell-phones and televisions at higher
      doses was associated with delayed sleep/wake schedules and wake lag, potentially
      impairing health and educational outcomes.

PMID- 25390035
TI  - High-ranked social science journal articles can be identified from early citation
      information.
AB  - Do citations accumulate too slowly in the social sciences to be used to assess
      the quality of recent articles? I investigate whether this is the case using
      citation data for all articles in economics and political science published in
      2006 and indexed in the Web of Science. I find that citations in the first two
      years after publication explain more than half of the variation in cumulative
      citations received over a longer period. Journal impact factors improve the
      correlation between the predicted and actual future ranks of journal articles
      when using citation data from 2006 alone but the effect declines sharply
      thereafter. Finally, more than half of the papers in the top 20% in 2012 were
      already in the top 20% in the year of publication (2006). 

PMID- 25390036
TI  - The avian head induces cues for sound localization in elevation.
AB  - Accurate sound source localization in three-dimensional space is essential for an
      animal's orientation and survival. While the horizontal position can be
      determined by interaural time and intensity differences, localization in
      elevation was thought to require external structures that modify sound before it
      reaches the tympanum. Here we show that in birds even without external structures
      like pinnae or feather ruffs, the simple shape of their head induces sound
      modifications that depend on the elevation of the source. Based on a model of
      localization errors, we show that these cues are sufficient to locate sounds in
      the vertical plane. These results suggest that the head of all birds induces
      acoustic cues for sound localization in the vertical plane, even in the absence
      of external ears. 

PMID- 25390037
TI  - Nanoparticle-based membrane assembly and silicification in coacervate
      microdroplets as a route to complex colloidosomes.
AB  - The chemical construction of complex colloidosomes consisting of a molecularly
      crowded polyelectrolyte-enriched interior surrounded by a continuous shell of
      closely packed silica nanoparticles is studied using optical and fluorescence
      microscopy, high-resolution X-ray microcomputed tomography, and synchrotron
      radiation X-ray tomographic microscopy. The colloidosomes are prepared by
      addition of partially hydrophobic silica nanoparticles to dodecane dispersions of
      positively or negatively charged coacervate microdroplets consisting of aqueous
      mixtures of poly(diallyldimethylammonium chloride) (PDDA) and adenosine 5'
      triphosphate (ATP) or PDDA and poly(acrylic acid) (PAA), respectively.
      Interfacial assembly of the nanoparticles produces a polydisperse population of
      well-defined PDDA/PAA droplets with diameters ranging from 50 to 950 MUm. In
      contrast, reconstruction of the PDDA/ATP coacervate interior occurs on addition
      of the silica nanoparticles to produce a nanoparticle-stabilized oil-in
      coacervate-in-oil multiphase emulsion. Transfer of the coacervate-containing
      colloidosomes into water and replication of their internal structure are achieved
      by addition of tetramethoxysilane, which serves as both a cross-linking and
      silicification agent to produce mineralized PDDA/PAA or PDDA/ATP microstructures
      with a uniform solidified texture or multichambered interior, respectively. The
      integration of colloidosome and coacervate technologies offers a route to a new
      type of multifunctional microcompartmentalized system based on the membrane
      mediated incarceration of molecularly crowded chemical environments. 

PMID- 25390038
TI  - Non-invasive MRI and spectroscopy of mdx mice reveal temporal changes in
      dystrophic muscle imaging and in energy deficits.
AB  - In Duchenne muscular dystrophy (DMD), a genetic disruption of dystrophin protein
      expression results in repeated muscle injury and chronic inflammation. Magnetic
      resonance imaging shows promise as a surrogate outcome measure in both DMD and
      rehabilitation medicine that is capable of predicting clinical benefit years in
      advance of functional outcome measures. The mdx mouse reproduces the dystrophin
      deficiency that causes DMD and is routinely used for preclinical drug testing.
      There is a need to develop sensitive, non-invasive outcome measures in the mdx
      model that can be readily translatable to human clinical trials. Here we report
      the use of magnetic resonance imaging and spectroscopy techniques for the non
      invasive monitoring of muscle damage in mdx mice. Using these techniques, we
      studied dystrophic mdx muscle in mice from 6 to 12 weeks of age, examining both
      the peak disease phase and natural recovery phase of the mdx disease course. T2
      and fat-suppressed imaging revealed significant levels of tissue with elevated
      signal intensity in mdx hindlimb muscles at all ages; spectroscopy revealed a
      significant deficiency of energy metabolites in 6-week-old mdx mice. As the mdx
      mice progressed from the peak disease stage to the recovery stage of disease,
      each of these phenotypes was either eliminated or reduced, and the cross
      sectional area of the mdx muscle was significantly increased when compared to
      that of wild-type mice. Histology indicates that hyper-intense MRI foci
      correspond to areas of dystrophic lesions containing inflammation as well as
      regenerating, degenerating and hypertrophied myofibers. Statistical sample size
      calculations provide several robust measures with the ability to detect
      intervention effects using small numbers of animals. These data establish a
      framework for further imaging or preclinical studies, and they support the
      development of MRI as a sensitive, non-invasive outcome measure for muscular
      dystrophy. 

PMID- 25390039
TI  - Homogeneous reduction of CO2 by photogenerated pyridinyl radicals.
AB  - We report that 1-hydropyridinyl radicals (1-PyH(*)) photogenerated in solution
      react with dissolved CO2 en route to its 2e(-) reduction into carboxylic acids.
      The 254 nm excitation of pyridine (Py) in deaerated 2-PrOH/H2O mixtures saturated
      with 1 atm of CO2 yields a suite of products, among which we identified
      Na(HCOO)2(-) (m/z(-) = 113), C5H6NCOO(-) (m/z(-) = 124), and C5H10O2NCOO(-) (m/z(
      ) = 160) species by electrospray ionization mass spectrometry. These products
      demonstrably contain carboxylate functionalities that split CO2 neutrals via
      collisionally induced dissociation. We infer that 1-PyH(*) [from (1) (3)Py* + 2
      PrOH -> 1-PyH(*) + (*)PrOH] adds to CO2, in competition with radical-radical
      reactions, leading to intermediates that are in turn reduced by (*)PrOH into the
      observed species. The formation of carboxylates in this system, which is shown to
      require CO2, Py, 2-PrOH, and actinic radiation, amounts to the homogeneous 2e(-)
      reduction of CO2 by 2-PrOH initiated by Py*. We evaluate a rate constant (2) k2(1
      PyH(*) + CO2 -> (*)Py-1-COOH) ~ O (10) M(-1) s(-1) and an activation energy E2 >=
      9 kcal mol(-1) that are compatible with thermochemical estimates for this
      reaction. 

PMID- 25390040
TI  - The B vitamins nicotinamide (B3) and riboflavin (B2) stimulate metamorphosis in
      larvae of the deposit-feeding polychaete Capitella teleta: implications for a
      sensory ligand-gated ion channel.
AB  - Marine sediments can contain B vitamins, presumably incorporated from settled,
      decaying phytoplankton and microorganisms associated with decomposition. Because
      B vitamins may be advantageous for the energetically intensive processes of
      metamorphosis, post-metamorphic growth, and reproduction, we tested several B
      vitamins to determine if they would stimulate larvae of the deposit-feeding
      polychaete Capitella teleta to settle and metamorphose. Nicotinamide and
      riboflavin individually stimulated larvae of C. teleta to settle and
      metamorphose, generally within 1-2 hours at nicotinamide concentrations as low as
      3 uM and riboflavin concentrations as low as 50 uM. More than 80% of the larvae
      metamorphosed within 30 minutes at a nicotinamide concentration of 7 uM. The
      pyridine channel agonist pyrazinecarboxamide also stimulated metamorphosis at
      very low concentrations. In contrast, neither lumichrome, thiamine HCl,
      pyridoxine HCl, nor vitamin B12 stimulated larvae of C. teleta to metamorphose at
      concentrations as high as 500 uM. Larvae also did not metamorphose in response to
      either nicotinamide or pyrazinecarboxamide in calcium-free seawater or with the
      addition of 4-acetylpyridine, a competitive inhibitor of the pyridine receptor.
      Together, these results suggest that larvae of C. teleta are responding to
      nicotinamide and riboflavin via a chemosensory pyridine receptor similar to that
      previously reported to be present on crayfish chela and involved with food
      recognition. Our data are the first to implicate B vitamins as possible natural
      chemical settlement cues for marine invertebrate larvae. 

PMID- 25390041
TI  - Worry about developing melanoma in the pigmented lesion clinic: does it warrant a
      solution?

PMID- 25390042
TI  - Chemopreventive efficacy of Andrographis paniculata on azoxymethane-induced
      aberrant colon crypt foci in vivo.
AB  - Andrographis paniculata is a grass-shaped medicinal herb, traditionally used in
      Southeast Asia. The aim of this study was to evaluate the chemoprotective effects
      of A. paniculata on colorectal cancer. A. paniculata ethanol extract was tested
      on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in vivo and in vitro. A.
      paniculata treated groups showed a significant reduction in the number of ACF of
      the treated rats. Microscopically, ACF showed remarkably elongated and stratified
      cells, and depletion of the submucosal glands of AOM group compared to the
      treated groups. Histologically, staining showed slightly elevated masses above
      the surrounding mucosa with oval or slit-like orifices. Immunohistochemically,
      expression of proliferating cell nuclear antigen (PCNA) and beta-catenin protein
      were down-regulated in the A. paniculata treated groups compared to the AOM
      group. When colon tissue was homogenized, malondialdehyde (MDA) and nitric oxide
      (NO) levels were significantly decreased, whereas superoxide dismutase (SOD)
      activity was increased in the treated groups compared to the AOM group. A.
      paniculata ethanol extract showed antioxidant and free radical scavenging
      activity, as elucidated by the measure of oxidative stress markers. Further, the
      active fractions were assessed against cell lines of CCD841 and HT29 colon cancer
      cells. 

PMID- 25390044
TI  - Development of an electronic medical record based alert for risk of HIV treatment
      failure in a low-resource setting.
AB  - BACKGROUND: The adoption of electronic medical record systems in resource-limited
      settings can help clinicians monitor patients' adherence to HIV antiretroviral
      therapy (ART) and identify patients at risk of future ART failure, allowing
      resources to be targeted to those most at risk. METHODS: Among adult patients
      enrolled on ART from 2005-2013 at two large, public-sector hospitals in Haiti,
      ART failure was assessed after 6-12 months on treatment, based on the World
      Health Organization's immunologic and clinical criteria. We identified models for
      predicting ART failure based on ART adherence measures and other patient
      characteristics. We assessed performance of candidate models using area under the
      receiver operating curve, and validated results using a randomly-split data
      sample. The selected prediction model was used to generate a risk score, and its
      ability to differentiate ART failure risk over a 42-month follow-up period was
      tested using stratified Kaplan Meier survival curves. RESULTS: Among 923 patients
      with CD4 results available during the period 6-12 months after ART initiation,
      196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days
      covered (PDC) measure performed best among five possible ART adherence measures
      at predicting ART failure. Average PDC during the first 6 months on ART was 79.0%
      among cases of ART failure and 88.6% among cases of non-failure (p<0.01). When
      additional information including sex, baseline CD4, and duration of enrollment in
      HIV care prior to ART initiation were added to PDC, the risk score differentiated
      between those who did and did not meet failure criteria over 42 months following
      ART initiation. CONCLUSIONS: Pharmacy data are most useful for new ART adherence
      alerts within iSante. Such alerts offer potential to help clinicians identify
      patients at high risk of ART failure so that they can be targeted with adherence
      support interventions, before ART failure occurs.

PMID- 25390045
TI  - Lewis base-catalyzed reaction of aziridinofullerene with ureas for the
      preparation of fulleroimidazolidinones.
AB  - The Lewis base-catalyzed double nucleophilic substitution reaction of N
      tosylaziridinofullerene with various ureas allows the easy preparation of
      fulleroimidazolidinones with a high tolerance for functional groups. Alkyl
      substituted ureas show better reactivity than aryl-substituted ureas. 

PMID- 25390046
TI  - Suppression of microbial metabolic pathways inhibits the generation of the human
      body odor component diacetyl by Staphylococcus spp.
AB  - Diacetyl (2,3-butanedione) is a key contributor to unpleasant odors emanating
      from the axillae, feet, and head regions. To investigate the mechanism of
      diacetyl generation on human skin, resident skin bacteria were tested for the
      ability to produce diacetyl via metabolism of the main organic acids contained in
      human sweat. L-lactate metabolism by Staphylococcus aureus and Staphylococcus
      epidermidis produced the highest amounts of diacetyl, as measured by high
      performance liquid chromatography. Glycyrrhiza glabra root extract (GGR) and
      alpha-tocopheryl-L-ascorbate-2-O-phosphate diester potassium salt (EPC-K1), a
      phosphate diester of alpha-tocopherol and ascorbic acid, effectively inhibited
      diacetyl formation without bactericidal effects. Moreover, a metabolic flux
      analysis revealed that GGR and EPC-K1 suppressed diacetyl formation by inhibiting
      extracellular bacterial conversion of L-lactate to pyruvate or by altering
      intracellular metabolic flow into the citrate cycle, respectively, highlighting
      fundamentally distinct mechanisms by GGR and EPC-K1 to suppress diacetyl
      formation. These results provide new insight into diacetyl metabolism by human
      skin bacteria and identify a regulatory mechanism of diacetyl formation that can
      facilitate the development of effective deodorant agents.

PMID- 25390047
TI  - Animal brucellosis in Egypt.
AB  - Brucellosis is a highly contagious zoonosis that affects the public health and
      economic performance of endemic as well as non-endemic countries. In developing
      nations, brucellosis is often a very common but neglected disease. The purpose of
      this review is to provide insight about brucellosis in animal populations in
      Egypt and help to understand the situation from 1986 to 2013. A total of 67
      national and international scientific publications on serological investigations,
      isolation, and biotyping studies from 1986 to 2013 were reviewed to verify the
      current status of brucellosis in animal populations in Egypt. Serological
      investigations within the national surveillance program give indirect proof for
      the presence of brucellosis in cattle, buffaloes, sheep, goats, and camels in
      Egypt. Serologic testing for brucellosis is a well-established procedure in
      Egypt, but most of the corresponding studies do not follow the scientific
      standards. B. melitensis biovar (bv) 3, B. abortus bv 1, and B. suis bv 1 have
      been isolated from farm animals and Nile catfish. Brucellosis is prevalent
      nationwide in many farm animal species. There is an obvious discrepancy between
      official seroprevalence data and data from scientific publications. The need for
      a nationwide survey to genotype circulating Brucellae is obvious. The
      epidemiologic situation of brucellosis in Egypt is unresolved and needs
      clarification.

PMID- 25390048
TI  - Abia State HIV epidemic and response: challenges and prospects.
AB  - Since the first seroprevalence survey in 1999, the HIV prevalence in Abia State
      has increased from 1.8% to 7.3% in 2010. The state is currently experiencing a
      generalized epidemic, with most transmission occurring through heterosexual low
      risk sex. Drivers of the epidemic include low knowledge of HIV prevention, low
      risk perception, predominantly male factor-driven risky sexual behavior, and low
      condom use. This study reviewed the state HIV epidemic trend in relation to
      response, sought to identify the gaps between the epidemic and response, and
      recommended measures to strengthen the state response.

PMID- 25390049
TI  - The current Ebola outbreak: old and new contexts.
AB  - Within the ongoing Ebola outbreak in West Africa, separate scenarios reflect old
      contexts with well-known strategies to face the epidemic on one side and
      completely new and unprecedented situations requiring new approaches on the other
      side. While Senegal and Nigeria represent success stories on the implementation
      of appropriate standard public health measures for containment, Liberia, Sierra
      Leone, and Guinea require a major and innovative scale of actions to halt even
      more catastrophic consequences. 

PMID- 25390050
TI  - Antimicrobial profile of Salmonella enterica serotype Choleraesuis from free
      range swine in Kakamega fish market, western Kenya.
AB  - INTRODUCTION: Salmonella enterica subspecies enterica serovar Choleraesuis is a
      host-adapted, facultative, intracellular pathogen that causes swine paratyphoid.
      Its antimicrobial resistance presents a challenge to feed manufacturing
      industries. However, stopping antibiotics in animal feed would have economic
      implications for the industry. METHODOLOGY: Conventional microbial methods for
      isolation and identification of S. Choleraesuis were employed. The isolates were
      subjected to screening against 17 antimicrobial agents and genotyping of
      resistance markers by PCR. The data were then analyzed and presented in
      percentages. RESULTS: Phenotypically, 43 out of 95 isolates showed multidrug
      resistance. Among the 17 antibiotics tested, resistance was observed as follows:
      sulphonamides (45.2%), nalidixic acid (44.25%), tetracycline (42%), ampicillin
      (36.8%), erythromycin (34.7%), carbenicillin (31.5%), chrolamphenical (28.4%),
      gentamicin (27.3%), kanamycin (24.2%), spectinomycin (21%), sulfamethoxazole
      trimethoprim (16.8%), streptomycin (12.6%), cephalothion (8.4%), ofloxacin
      (5.2%), ciprofloxacin (4.2%), and norfloxacin (4.2%). Fifty-two isolates were
      susceptible to the antimicrobial agents tested. A total of 3.1% of the isolates
      had the integron gene pattern combination of dfrA2-aadA2 (2100 bp), dfrA12 (2100
      bp); 4.2% had dfrA12-aadA2-sulI (2100 bp); 2.1% had dfrA12-aadA2 (2100 bp); and
      1% had dfrA2-aadA2-sulI (2100 bp), oxa1-aadA2 (1500 bp), dfrA12-aadA2-sulI, and
      blaPSE (2100 bp). CONCLUSIONS: The isolated S. Choleraesuis were resistant to
      more than 10% of the antimicrobial agents used in this study. Appropriate
      surveillance is warranted to gain more information about the epidemiology, as
      stopping antibiotics in animal feed would have economic implications for the
      industry.

PMID- 25390051
TI  - Antibiotic resistant Shigella is a major cause of diarrhoea in the Highlands of
      Papua New Guinea.
AB  - INTRODUCTION: Diarrhoea remains a major cause of illness in Papua New Guinea
      (PNG); however, little is known about its aetiology. As a result of the cholera
      outbreak that spread throughout PNG in 2009-2011, we conducted diarrhoeal
      surveillance in Eastern Highlands Province. METHODOLOGY: Following informed
      consent and a brief questionnaire, participants provided a stool sample or
      duplicate rectal swabs. Samples were tested for common bacterial pathogens
      Salmonella spp., Shigella spp., Vibrio spp., Campylobacter spp. and Yersinia
      enterocolitica using established culture methods. Enteric parasites were detected
      using microscopy. RESULTS: A total of 216 participants were enrolled; where age
      was recorded, 42% were under 5 years of age, 6.7% were 5 to 17 years of age and
      51.3% >=18 years of age. One or more pathogens were detected in 68 (31.5%)
      participants, with Shigella (primarily S. flexneri) being the most commonly
      isolated (47 of 216 participants). Enteric parasites were detected in 23 of the
      216 participants, occurring as a co-infection with another pathogen in 12 of 23
      cases. No Vibrio cholerae was detected. Shigella isolates were commonly resistant
      to ampicillin, tetracycline, co-trimoxazole and chloramphenicol. CONCLUSIONS:
      Shigellae, specifically S. flexneri, are important pathogens in the highlands of
      PNG. While most studies in low-income settings focus on childhood aetiology, we
      have demonstrated the importance of Shigella in both children and adults. Enteric
      parasites remain present and presumably contribute to the burden of
      gastrointestinal illness. While improvements in sanitation and hygiene would help
      lower the burden of all aetiologies of infectious diarrhoea, additional control
      strategies targeting Shigella may also be warranted.

PMID- 25390052
TI  - Detection of putative virulence genes in Aeromonas isolates from humans and
      animals.
AB  - INTRODUCTION: Aeromonas are food- and water-borne bacteria that are considered to
      be zoonotic human pathogens. This study aimed to investigate the presence of
      genes associated with virulence in human and animal Aeromonas isolates and the
      potential role of animal isolates with regards to human Aeromonas infections.
      METHODOLOGY: The presence of aerA, hlyA, alt, ast, laf, ascF-G, stx1 and stx2
      putative virulence genes in 40 human and animal Aeromonas isolates (16 human and
      24 animal isolates) were examined by polymerase chain reaction (PCR). DNA
      fragments of expected sizes were purified and sequenced. BLAST in the NCBI was
      used to verify any amplified products. RESULTS: PCR screening showed that hlyA,
      alt, and laf genes were determined at ratios of 6.25%, 50%, and 6.25%,
      respectively, in human isolates. The ratios of hlyA, alt, ascF-G, laf, stx2, and
      stx1 genes in animal isolates were 58.3%, 20.83%, 33.3%, 20.83%, 8.33%, and
      4.17%, respectively. Neither aerA nor ast genes were detected in any isolates.
      Any one of eight putative virulence genes was not detected in seven human and
      eight animal isolates in the study. CONCLUSIONS: The current study is the first
      to investigate the presence of the virulence gene in gull Aeromonas isolates. The
      manifestation of the presence of the virulence gene and gene combinations was
      considerable, especially in fish and gull isolates when compared with clinical
      human isolates. The current study demonstrates the potential importance of fish
      and gulls in terms of human Aeromonas infections.

PMID- 25390053
TI  - Foodborne bacterial pathogens recovered from contaminated shawarma meat in
      northern Jordan.
AB  - INTRODUCTION: The purpose of the study was to isolate, identify, and determine
      the antimicrobial resistance of the bacterial pathogens recovered from shawarma
      (donair) sandwiches served to the public in Jordan. METHODOLOGY: Bacterial
      contamination of 100 shawarma sandwiches with pathogenic bacteria was studied by
      culture on selective media, serology, PCR assay, and antimicrobial susceptibility
      testing. RESULTS: One hundred and forty-five bacterial isolates were identified.
      The predominant species was Escherichia coli (28.3%), with six isolates of
      serotype O157:H7, followed by Salmonella spp. (25.5%). Higher contamination rates
      were found in chicken sandwiches. The majority of these bacteria expressed high
      resistance to several antimicrobials, especially tetracycline and streptomycin.
      Citrobacter freundii was isolated from 15.9% and Staphylococcus aureus was
      isolated from 8.3% of the sandwiches. The presence of these pathogens is of
      primary concern because some strains are capable of producing a heat-stable
      enterotoxin that causes food poisoning in humans, and should therefore be taken
      into account in risk assessment. CONCLUSIONS: Results signify the importance of
      sustained surveillance of foodborne pathogens in shawarma sandwiches to minimize
      the risk of contamination. Availability of data on the isolated pathogens and
      modes of transmission in food from different countries would provide a common
      ground for reaching international agreement on food safety regulations.

PMID- 25390054
TI  - Three-year study of health care-associated infections in a Turkish pediatric
      ward.
AB  - INTRODUCTION: Health care-associated infections (HCAIs) can cause an increase in
      morbidity, mortality and costs, especially in developing countries. As
      information on the epidemiology of HCAIs in pediatric patientsinTurkey is
      limited, we decided to study the annual incidence and antibiotic resistance
      patterns in our pediatric ward at Marmara University Hospital. METHODOLOGY: All
      hospitalized patients in the pediatric ward were assessed with regard to HCAIs
      between January 1, 2008 and December 31, 2010. Data was prospectively collected
      according to standard protocols of the National Nosocomial Infections
      Surveillance System (NosoLINE). RESULTS: A total of 16.5% of all hospitalized
      patients developed HCAIs in the three years studied. The most frequent HCAIs were
      urinary tract infections (UTI) (29.3%), bloodstream infections (27%) and
      pneumonias (21%). While the most frequent agent isolatedfrom UTI was Escherichia
      coli (26%), the most common agent in blood stream infections was Staphylococcus
      epidermidis (30.4%). Vancomycin resistance was found in 73.3% of all Enterococcus
      faecium strains. Extended-spectrum beta-lactamase was detected in 58.3% of
      Klebsiella pneumoniae and E. coli isolates. CONCLUSIONS: Continual HCAI
      surveillance is important to determineits rate. Knowledge of the HCAI incidence
      can influence people's use of broad-spectrum antibiotics and encourage antibiotic
      rotation. Moreover, the knowledge of HCAI incidence may support the infection
      control programmes, including education and isolation methods which ultimately
      may help to reducethe rate of the HCAIs.

PMID- 25390055
TI  - Glial alterations in tuberculous and cryptococcal meningitis and their relation
      to HIV co-infection--a study on human brains.
AB  - INTRODUCTION: Tuberculosis and cryptococcal infection of the central nervous
      system are common AIDS-associated opportunistic infections in tropical
      underdeveloped and developing countries. To date, research on these infections
      has focused on clinical, imaging, laboratory diagnosis, and animal models to
      elucidate the pathogenesis. There is paucity of information on astroglial and
      microglial alterations in the human nervous system following these infections.
      METHODOLOGY: The pathomorphologic and morphometric alterations of astroglia and
      microglia in the prefrontal cortex and hippocampus in cases of tuberculous
      meningitis (TBM) and cryptococcal meningitis (CM) with and without associated HIV
      were described and compared with cases of HIV encephalitis without opportunistic
      infections (OI) and HIV-negative human brain tissue. RESULTS: In TBM, the
      microglia and astrocytes were activated with hypertrophy and hyperplasia,
      aggregating in the subpial zone and around granulomas in meningeal exudate. In
      cases of cryptococcal meningitis, reactive changes were less prominent, though
      activation of both cellular elements was found. Association of HIV with these OIs
      resulted in muted glial and microglial response. In HIV encephalitis without OI,
      the level of activation of was low. Both astroglial and microglial cells
      expressed caspase-3, a pro-apoptotic marker, following HIV and opportunistic
      infections. Neuronal apoptosis, a mechanism to ensure neuronal survival, was less
      evident. The reactive astrocytes and microglia following opportunistic infection
      developed dystrophic changes heralding senescence. CONCLUSIONS: Further studies
      on neuronal-astroglial-microglial interaction will offer deeper insight into the
      pathogenetic and immune mechanisms in the cellular and pathomorphological
      evolution of tuberculous and cryptococcal infections.

PMID- 25390056
TI  - HAART and liver: is it safe?
AB  - INTRODUCTION: Liver disease caused by hepatitis C virus (HCV) is a major cause of
      morbidity in HIV patients. This study investigates the possibility that chronic
      HCV increases the risk of hepatotoxicity after highly active antiretroviral
      therapy (HAART) initiation. METHODOLOGY: The data from 30 coinfected HIV/HCV and
      35 HIV monoinfected patients between August 2008 and August 2010, since the start
      of HAART, were analyzed along with data from every three months, with
      clinical/laboratory evaluation until the end of twelve months. The aim of this
      study was to assess risk and incidence of hepatotoxicity in both groups. RESULTS:
      Before the introduction of HAART, coinfected patients had higher average levels
      of transaminases than did the monoinfected group (p < 0.001). After initiation of
      HAART, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels
      were higher in coinfected patients, regardless of type of HAART they received.
      Twenty-two (73%) of the coinfected patients had some degree of hepatotoxicity
      versus only seven (20%) of the monoinfected patients. No patient had severe
      hepatotoxicity. Risk of hepatotoxicity after HAART in a coinfected patient was
      3.7 times higher than in a monoinfected patient (RR 3.7 [1.8-7.4], p < 0.001).
      CONCLUSIONS: This study demonstrates that coinfected patients are at an increased
      risk for developing hepatotoxicity, but the clinical and immunological benefits
      of HAART are higher than the risk of hepatotoxicity and rarely justify
      discontinuation of therapy.

PMID- 25390057
TI  - Fasciola hepatica infection at a University Clinic in Turkey.
AB  - INTRODUCTION: We aimed to analyze the approaches to the diagnosis and treatment
      of patients with fascioliasis in light of current literature. METHODOLOGY: Thirty
      nine patients with fascioliasis admitted to the Surgery Clinic of Dicle Medical
      Faculty (Turkey) were included in this study. The demographic, clinical,
      diagnostic, treatment and outcome data were analyzed retrospectively. RESULTS:
      Abdominal pain (n = 37; 95%) and eosinophilia (n = 31; 79%) were the most common
      findings. Twenty-seven patients were diagnosed by clinical and radiological
      findings. Patients were treated with triclabendazole. Thirty-six (92.4%) of the
      patients improved after medical treatment. CONCLUSIONS: The presence of typical
      clinical, laboratory and radiological findings is sufficient for diagnosis.
      Triclabendazole administration is often an effective treatment, with improvements
      occurring over the course of a few months.

PMID- 25390058
TI  - Tungiasis in Northern Tanzania: a clinical report from Qameyu village, Babati
      District, Manyara Region.
AB  - INTRODUCTION: Tungiasis is an infestation caused by the penetration in the skin
      of the gravid female of the flea Tunga penetrans (T. penetrans). The current
      epidemiological situation of tungiasis in Eastern Africa is poorly known. We
      present the results of a cross-sectional study on tungiasis which was carried out
      in Qameyu (Northern Tanzania). METHODOLOGY: Sixty-two schoolchildren with
      suspected cases of tungiasis were examined. Location, number, morphology and
      symptoms associated with T. penetrans infestation were recorded for each patient.
      RESULTS: A total of 62 schoolchildren (38 males and 24 females), with ages
      ranging from 6 to 14 years, were examined. Sixty children were infested by T.
      penetrans. A total of 865 lesions were observed: 170 lesions were vital and 695
      were non-vital. The first and the fifth toes were especially involved. The
      highest number of lesions observed in a single patient was more than 55 lesions.
      Pain was reported by 42 children, itching by 39 and difficult walking by 28. One
      child presented with fever which was considered to be caused by superinfected
      tungiasis. Complications were nail dystrophy (48 patients), deformity of the
      fingers or toes (12 patients), scarring (4 patients) and nail loss (4 patients).
      Thirteen children needed oral antibiotic therapy because of bacterial
      superinfections. CONCLUSIONS: Tungiasis is a public health concern in this region
      of Tanzania and it is associated with high morbidity. Improvement in housing
      hygiene, confining domestic animals and increasing the knowledge of the disease
      via health education are measures that should be taken to control the disease.

PMID- 25390059
TI  - Association between intoxication at last sexual intercourse and unprotected sex
      among men and women in Uganda.
AB  - INTRODUCTION: This study examined the association between intoxication at last
      sexual intercourse and unprotected sex using data derived from a nationally
      representative survey conducted in Uganda in 2011. METHODOLOGY: Multivariable
      logistic regression analyses were used to examine the intoxication-unprotected
      sex association separately among men and women, adjusted for sociodemographic and
      behavioral covariates that were also examined as moderators of the association.
      RESULTS: Among men, intoxication at last sexual intercourse was almost entirely
      attributed to their own drinking, while women most frequently reported
      intoxication among their partners only. Among women, there was a significant
      association between their partner's intoxication and unprotected sex (adjusted
      odds ratio (AOR) = 1.36; 95% confidence interval (CI) = 1.07-1.73. Intoxication
      was associated with unprotected sex among unmarried men (AOR = 2.09; 95%; CI =
      1.45-2.84), an association not observed among married men. CONCLUSIONS: The
      results suggest that the alcohol-unprotected sex link should be incorporated
      within Ugandan National HIV Prevention Strategy. These interventions should be
      designed to target unmarried men. Programs that combine alcohol reduction and
      address structural factors that constrain women's ability to negotiate condom use
      are also needed.

PMID- 25390060
TI  - Infection remains a leading cause of neonatal mortality among infants delivered
      at a tertiary hospital in Karachi, Pakistan.
AB  - INTRODUCTION: The current cohort study was conducted to determine the frequency
      and compare the mortality rate with associated characteristics among low birth
      weight and normal birth weight infants during the neonatal period at a tertiary
      healthcare facility, Karachi. METHODOLOGY: Close-ended structured questionnaires
      were used to collect information from the parents of 500 registered neonates at
      the time of birth. Follow-ups by phone on the 28th day of life were done to
      determine the mortality among low birth weight and normal birth weight babies
      during the neonatal period. RESULTS: The neonatal mortality rate ranged from as
      low as 2.4% in the normal birth weight and 16.4% in the low birth weight
      categories to as high as 96% in the very low birth weight category. Respiratory
      distress syndrome (24.2%) and sepsis (18.2%) were reported as the leading causes
      of neonatal deaths. The babies' lengths of stay ranged from 2 to 24 hours, and
      around 90% of neonatal deaths were reported in the first seven days of life. More
      than 6% of neonates died at home, and 7.6% of the deceased babies did not visit
      any healthcare facility or doctor before their death. In the 12-15 hours before
      their deaths, 13.6% of the deceased babies had been unattended. Around 90% of the
      deceased babies were referred from a doctor or healthcare facility. CONCLUSIONS:
      The present estimates of neonatal mortality are very high among low birth weight
      and very low birth weight categories. Infectious diseases, including respiratory
      distress syndrome (24.2%) and sepsis (18.2%), were leading causes of neonatal
      deaths.

PMID- 25390061
TI  - Use of port-a-cath in cancer patients: a single-center experience.
AB  - INTRODUCTION: Central venous catheters play an important role in the management
      of cancer patients. Different types of devices are associated with different
      patterns of complications. We report on the pattern of use and rate of
      complications of port-a-caths in patients diagnosed with malignant cancer at a
      single institution. METHODOLOGY: The data were collected retrospectively from
      patients who received the treatment for solid tumors or lymphoma through a port-a
      cath at the Sultan Qaboos University Hospital (SQUH) between January 2007 and
      February 2013. RESULTS: A total of 117 port-a-caths were inserted in 106
      patients. The majority (86; 73.5%) were implanted by an interventional
      radiologist, and the right internal jugular vein was accessed in 79 (67.5%)
      patients. Mean catheter indwelling time was 354 (range 3-1,876) days for all
      patients, 252 (3-1,876) and 389 days (13-1,139) for patients with and without
      complications, respectively. Thirty (25.6%) port-a-caths were removed
      prematurely, mainly due to infectious complications, while 17 (14.5%) were
      removed after completion of treatment. Staphylococcus aureus was the most
      frequently isolated organism, found in 8 (6.8%) patients. Underlying diagnosis (p
      < 0.001), chemotherapy regimen (p < 0.001), sensitivity to antibiotics (p =
      0.01), and any complication (p < 0.001) were significant factors affecting the
      duration of port-a-cath use. None of these factors were significant on
      multivariate cox regression analysis. CONCLUSIONS: The mean duration of port-a
      cath use was almost one year. Infection was the most common complication leading
      to premature removal, followed by port thrombosis.

PMID- 25390062
TI  - Re-emergence of susceptibility to conventional first line drugs in Salmonella
      isolates from enteric fever patients in Nepal.
AB  - INTRODUCTION: Enteric fever is endemic in Nepal and poses a significant public
      health burden. The first-line drugs ampicillin, chloramphenicol, and
      cotrimoxazole have not been part of empirical therapy for two decades due to the
      development of multidrug-resistant Salmonella strains. The objective of this
      study was to determine the antibiogram pattern of Salmonella serovars isolated
      from the blood of clinically suspected enteric fever patients. METHODOLOGY: A
      cross sectional study was carried out in a tertiary care hospital in Lalitpur,
      Nepal, between July 2011 and February 2012. Standard microbiological procedures
      were followed during collection and processing of blood samples, isolation and
      identification of Salmonella serotypes. The antimicrobial sensitivity of
      ampicillin, chloramphenicol, cotrimoxazole, nalidixic acid, and ciprofloxacin was
      determined using a modified Kirby-Bauer disk diffusion method as per the
      guidelines of the Clinical and Laboratory Standards Institute. RESULTS: Out of 86
      Salmonella isolates, 56 (65.1%) were Salmonella Typhi and 30 (34.9%) were
      Salmonella Paratyphi A. Salmonella Typhi were 100% sensitive to chloramphenicol,
      cotrimoxazole, and ciprofloxacin and 98.2% sensitive to ampicillin. Similarly,
      Salmonella Paratyphi A isolates were 100% sensitive to ampicillin and
      cotrimoxazole and 96.7% sensitive to chloramphenicol and ciprofloxacin. More than
      90.0% of isolates were nalidixic acid resistant and none of the Salmonella
      isolates were multi-drug resistant. CONCLUSIONS: This study revealed the
      increasing frequency of nalidixic acid-resistant Salmonella isolates, indicating
      the possibility of fluoroquinolone resistance in near future. Furthermore, re
      emergence of susceptibility to conventional first-line drugs ampicillin,
      chloramphenicol, and cotrimoxazole supports the possibility of using these drugs
      in empirical therapy.

PMID- 25390063
TI  - Group G Streptococci in association with brain abscess: a rare occurrence.
AB  - Brain abscess is a serious life-threatening infection of the brain parenchyma. We
      are reporting a rare case of brain abscess caused by Group G Streptococcus in a
      12 year-old female child who presented with neurological symptoms. She was
      diagnosed with congenital anomalies of the heart at birth. She was treated with
      amoxyclav and ciprofloxacin. The child recovered and was discharged uneventfully.

PMID- 25390064
TI  - Liver abscess associated with severe myopathy caused by Klebsiella pneumoniae
      serotype K1 in Romania.
AB  - Liver abscess was diagnosed in a man presenting with fever, chills and severe
      myopathy. The K. pneumoniae isolated from blood cultures belonged to the K1
      serotype. The patient responded favourably to percutaneous drainage of the
      abscess and antibiotics. This is the first documented report of Klebsiella
      pneumoniae liver abscess syndrome (KLAS) described in Romania and may indicate
      the emergence of this syndrome in Eastern Europe.

PMID- 25390065
TI  - Multisystem involvement of alveolar echinococcosis in a child.
AB  - Alveolar echinococcosis (AE) is a chronic progressive infestation inducing a
      slowly progressing, life-threatening tumor-like growth in the liver. It may
      spread to other organs by regional extension or hematogenous or lymphatic
      metastasis. Herein, we report a fifteen-year-old patient diagnosed with AE of the
      liver and simultaneous lung and brain metastasis with a literature review.

PMID- 25390066
TI  - Pseudomonas aeruginosa infection in burn patients in Sulaimaniyah, Iraq: risk
      factors and antibiotic resistance rates.

PMID- 25390067
TI  - Adaptable neighbours: movement patterns of GPS-collared leopards in human
      dominated landscapes in India.
AB  - Understanding the nature of the interactions between humans and wildlife is of
      vital importance for conflict mitigation. We equipped five leopards with GPS
      collars in Maharashtra (4) and Himachal Pradesh (1), India, to study movement
      patterns in human-dominated landscapes outside protected areas. An adult male and
      an adult female were both translocated 52 km, and exhibited extensive, and
      directional, post release movements (straight line movements: male = 89 km in 37
      days, female = 45 km in 5 months), until they settled in home ranges of 42 km2
      (male) and 65 km2 (female). The three other leopards, two adult females and a
      young male were released close to their capture sites and used small home ranges
      of 8 km2 (male), 11 km2 and 15 km2 (females). Movement patterns were markedly
      nocturnal, with hourly step lengths averaging 339+/-9.5 m (SE) during night and
      60+/-4.1 m during day, and night locations were significantly closer to human
      settlements than day locations. However, more nocturnal movements were observed
      among those three living in the areas with high human population densities. These
      visited houses regularly at nighttime (20% of locations <25 m from houses), but
      rarely during day (<1%). One leopard living in a sparsely populated area avoided
      human settlements both day and night. The small home ranges of the leopards
      indicate that anthropogenic food resources may be plentiful although wild prey is
      absent. The study provides clear insights into the ability of leopards to live
      and move in landscapes that are extremely modified by human activity.

PMID- 25390068
TI  - BMP-7 enhances cell migration and alphavbeta3 integrin expression via a c-Src
      dependent pathway in human chondrosarcoma cells.
AB  - Bone morphogenic protein (BMP)-7 is a member of the transforming growth factor
      (TGF)-beta superfamily, which is originally identified based on its ability to
      induce cartilage and bone formation. In recent years, BMP-7 is also defined as a
      potent promoter of cell motility, invasion, and metastasis. However, there is
      little knowledge of the role of BMP-7 and its cellular function in chondrosarcoma
      cells. In the present study, we investigated the biological impact of BMP-7 on
      cell motility using transwell assay. In addition, the intracellular signaling
      pathways were also investigated by pharmacological and genetic approaches. Our
      results demonstrated that treatment with exogenous BMP-7 markedly increased cell
      migration by activating c-Src/PI3K/Akt/IKK/NF-kappaB signaling pathway, resulting
      in the transactivation of alphavbeta3 integrin expression. Indeed, abrogation of
      signaling activation, by chemical inhibition or expression of a kinase dead form
      of the protein attenuated BMP-7-induced expression of integrin alphavbeta3 and
      cell migration. These findings may provide a useful tool for
      diagnostic/prognostic purposes and even therapeutically in late-stage
      chondrosarcoma as an anti-metastatic agent. 

PMID- 25390070
TI  - Anisotropic polymer composites synthesized by immobilizing cellulose nanocrystal
      suspensions specifically oriented under magnetic fields.
AB  - Novel polymer composites reinforced with an oriented cellulose nanocrystal (CNC)
      assembly were prepared from suspensions of CNC in aqueous 2-hydroxyethyl
      methacrylate (HEMA) via magnetic field application to the suspensions followed by
      polymerization treatment. The starting suspensions used at ~6 wt % CNC separated
      into an upper isotropic phase and a lower anisotropic (chiral nematic) one in the
      course of quiescent standing. A static or rotational magnetic field was applied
      to the isolated isotropic and anisotropic phases. UV-induced polymerization of
      HEMA perpetuated the respective states of magnetic orientation invested for the
      CNC dispersions to yield variously oriented CNC/poly(2-hydroxyethyl methacrylate)
      composites. The structural characterization was carried out by use of X-ray
      diffractometry and optical and scanning electron microscopy. The result indicated
      that CNCs were aligned in the composites distinctively according to the static or
      rotational magnetic application when the anisotropic phases were used, whereas
      such a specific CNC orientation was not appreciable when the isotropic phases
      were sampled. This marks out effectiveness of a coherent response of CNCs in the
      mesomorphic assembly. In dynamic mechanical experiments in tensile or compressive
      mode, we observed a clear mechanical anisotropy for the polymer composites
      synthesized from wholly anisotropic suspensions under static or rotational
      magnetization. The higher modulus (in compression) was detected for a composite
      reinforced by locking-in the uniaxial CNC alignment attainable through conversion
      of the initial chiral nematic phase into a nematic phase in the rotational
      magnetic field.

PMID- 25390069
TI  - Proximal tubule epithelial cell specific ablation of the spermidine/spermine N1
      acetyltransferase gene reduces the severity of renal ischemia/reperfusion injury.
AB  - BACKGROUND: Expression and activity of spermidine/spermine N1-acetyltransferase
      (SSAT) increases in kidneys subjected to ischemia/reperfusion (I/R) injury, while
      its ablation reduces the severity of such injuries. These results suggest that
      increased SSAT levels contribute to organ injury; however, the role of SSAT
      specifically expressed in proximal tubule epithelial cells, which are the primary
      targets of I/R injury, in the mediation of renal damage remains unresolved.
      METHODS: Severity of I/R injury in wt and renal proximal tubule specific SSAT-ko
      mice (PT-SSAT-Cko) subjected to bilateral renal I/R injury was assessed using
      cellular and molecular biological approaches. RESULTS: Severity of the loss of
      kidney function and tubular damage are reduced in PT-SSAT-Cko- compared to wt
      mice after I/R injury. In addition, animals treated with MDL72527, an inhibitor
      of polyamine oxidases, had less severe renal damage than their vehicle treated
      counter-parts. The renal expression of HMGB 1 and Toll like receptors (TLR) 2 and
      4 were also reduced in PT-SSAT-Cko- compared to wt mice after I/R injury.
      Furthermore, infiltration of neutrophils, as well as expression of tumor necrosis
      factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and
      interleukin-6 (IL-6) transcripts were lower in the kidneys of PT-SSAT-Cko
      compared to wt mice after I/R injury. Finally, the activation of caspase3 was
      more pronounced in the wt compared to PT-SSAT-Cko animals. CONCLUSIONS: Enhanced
      SSAT expression by proximal tubule epithelial cells leads to tubular damage, and
      its deficiency reduces the severity of renal I/R injury through reduction of
      cellular damage and modulation of the innate immune response.

PMID- 25390071
TI  - Physical activity during work, transport and leisure in Germany--prevalence and
      socio-demographic correlates.
AB  - BACKGROUND: This study aimed 1) to provide data estimates concerning overall
      moderate- and vigorous-intensity physical activity (MVPA) as well as MVPA during
      work, transport and leisure in Germany and 2) to investigate MVPA and possible
      associations with socio-demographic correlates. METHODS: A cross-sectional
      telephone survey interviewed 2248 representative participants in the age of 18-65
      years (1077 men; 42.4 +/- 13.4 years; body mass index: 25.3 +/- 4.5 kg * m(-2))
      regarding their self-reported physical activity across Germany. The Global
      Physical Activity Questionnaire was applied to investigate MVPA during work,
      transport and leisure and questions were answered concerning their demographics.
      MVPA was stratified by gender, age, body mass index, residential setting,
      educational and income level. To identify socio-demographic correlates of overall
      MVPA as well as in the domains, we used a series of linear regressions. RESULTS:
      52.8% of the sample achieved physical activity recommendations (53.7% men/52.1%
      women). Overall MVPA was highest in the age group 18-29 years (p < .05), in
      participants with 10 years of education (p < .05) and in participants with lowest
      income levels < 1.500 ? (p < .05). Regression analyses revealed that age,
      education and income were negatively associated with overall and work MVPA.
      Residential setting and education was positively correlated with transport MVPA,
      whereas income level was negatively associated with transport MVPA. Education was
      the only correlate for leisure MVPA with a positive association. CONCLUSIONS: The
      present data underlines the importance of a comprehensive view on physical
      activity engagement according to the different physical activity domains and
      discloses a need for future physical activity interventions that consider socio
      demographic variables, residential setting as well as the physical activity
      domain in Germany.

PMID- 25390072
TI  - Analysis of solvation and gelation behavior of methylcellulose using atomistic
      molecular dynamics simulations.
AB  - We adopt atomistic molecular dynamics (MD) simulations to study the solvation and
      gelation behavior of homogeneous methylcellulose (MC) and model random oligomers
      that represent the commercial cellulosic polymer product METHOCEL A in water and
      acetone solvents. We demonstrate that the two carbohydrate-specific GROMOS force
      fields, GROMOS 45A4 and 56Acarbo, are capable of reproducing characteristic angle
      distributions and the persistence length of MC chains reported in the literature.
      We then use the GROMOS 56Acarbo force field in both single-chain and multiple
      chain simulations to characterize their solvation behavior through radial
      distribution functions, hydrogen-bond counts, and contact map analyses. We find
      that the un-methylated O6 position on the cellulose ring forms the most hydrogen
      bonds, followed by O2 and O3, implying that methylation at the 6 position reduces
      hydrogen bonding more than does methylation at other positions. O6-O6 is the most
      probable intermolecular hydrogen bond between different MC molecules.
      Dimethylated and trimethylated MCs form aggregated structures at low temperatures
      and precipitate-like structures at high temperatures in water but disperse
      randomly in acetone. This is consistent with experimental observations of
      gelation at elevated temperatures in water. The heterogeneous METHOCEL A model
      shows increased aggregation of trimethylated monomer units at elevated
      temperatures, suggesting that hydrophobic interaction is the main factor that
      induces the gelation, rather than hydrogen bonding. 

PMID- 25390073
TI  - Size- and composition-dependent radio frequency magnetic permeability of iron
      oxide nanocrystals.
AB  - We investigate the size- and composition-dependent ac magnetic permeability of
      superparamagnetic iron oxide nanocrystals for radio frequency (RF) applications.
      The nanocrystals are obtained through high-temperature decomposition synthesis,
      and their stoichiometry is determined by Mossbauer spectroscopy. Two sets of
      oxides are studied: (a) as-synthesized magnetite-rich and (b) aged maghemite
      nanocrystals. All nanocrystalline samples are confirmed to be in the
      superparamagnetic state at room temperature by SQUID magnetometry. Through the
      one-turn inductor method, the ac magnetic properties of the nanocrystalline
      oxides are characterized. In magnetite-rich iron oxide nanocrystals, size
      dependent magnetic permeability is not observed, while maghemite iron oxide
      nanocrystals show clear size dependence. The inductance, resistance, and quality
      factor of hand-wound inductors with a superparamagnetic composite core are
      measured. The superparamagnetic nanocrystals are successfully embedded into hand
      wound inductors to function as inductor cores. 

PMID- 25390074
TI  - Structure identification in high-resolution transmission electron microscopic
      images: an example on graphene.
AB  - A connection between microscopic structure and macroscopic properties is expected
      for almost all material systems. High-resolution transmission electron microscopy
      is a technique offering insight into the atomic structure, but the analysis of
      large image series can be time consuming. The present work describes a method to
      automatically estimate the atomic structure in two-dimensional materials. As an
      example graphene is chosen, in which the positions of the carbon atoms are
      reconstructed. Lattice parameters are extracted in the frequency domain and an
      initial atom positioning is estimated. Next, a plausible neighborhood structure
      is estimated. Finally, atom positions are adjusted by simulation of a Markov
      random field model, integrating image evidence and the strong geometric prior. A
      pristine sample with high regularity and a sample with an induced hole are
      analyzed. False discovery rate-controlled large-scale simultaneous hypothesis
      testing is used as a statistical framework for interpretation of results. The
      first sample yields, as expected, a homogeneous distribution of carbon-carbon (C
      C) bond lengths. The second sample exhibits regions of shorter C-C bond lengths
      with a preferred orientation, suggesting either strain in the structure or a
      buckling of the graphene sheet. The precision of the method is demonstrated on
      simulated model structures and by its application to multiple exposures of the
      two graphene samples. 

PMID- 25390075
TI  - Soot aggregate restructuring due to coatings of secondary organic aerosol derived
      from aromatic precursors.
AB  - Restructuring of monodisperse soot aggregates due to coatings of secondary
      organic aerosol (SOA) derived from hydroxyl radical-initiated oxidation of
      toluene, p-xylene, ethylbenzene, and benzene was investigated in a series of
      photo-oxidation (smog) chamber experiments. Soot aggregates were generated by
      combustion of ethylene using a McKenna burner, treated by denuding, size-selected
      by a differential mobility analyzer, and injected into a smog chamber, where they
      were exposed to low vapor pressure products of aromatic hydrocarbon oxidation,
      which formed SOA coatings. Aggregate restructuring began once a threshold coating
      mass was reached, and the degree of the subsequent restructuring increased with
      mass growth factor. Although significantly compacted, fully processed aggregates
      were not spherical, with a mass-mobility exponent of 2.78, so additional SOA was
      required to fill indentations between collapsed branches of the restructured
      aggregates before the dynamic shape factor of coated particles approached 1.
      Trends in diameter growth factor, effective density, and dynamic shape factor
      with increasing mass growth factor indicate distinct stages in soot aggregate
      processing by SOA coatings. The final degree and coating mass dependence of soot
      restructuring were found to be the same for SOA coatings from all four aromatic
      precursors, indicating that the surface tensions of the SOA coatings are similar.

PMID- 25390076
TI  - Promoting evidence-based practice through a research training program for point
      of-care clinicians.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of a research
      training program on clinicians' knowledge, attitudes, and practices related to
      research and evidence-based practice (EBP). BACKGROUND: EBP has been shown to
      improve patient care and outcomes. Innovative approaches are needed to overcome
      individual and organizational barriers to EBP. METHODS: Mixed-methods design was
      used to evaluate a research training intervention with point-of-care clinicians
      in a Canadian urban health organization. Participants completed the Knowledge,
      Attitudes, and Practice Survey over 3 timepoints. Focus groups and interviews
      were also conducted. RESULTS: Statistically significant improvement in research
      knowledge and ability was demonstrated. Participants and administrators
      identified benefits of the training program, including the impact on EBP.
      CONCLUSIONS: Providing research training opportunities to point-of-care
      clinicians is a promising strategy for healthcare organizations seeking to
      promote EBP, empower clinicians, and showcase excellence in clinical research.

PMID- 25390079
TI  - Familial bilateral polypoidal choroidal vasculopathy.
AB  - PURPOSE: Description of the clinical and angiographic manifestations of
      polypoidal choroidal vasculopathy (PCV) in two brothers of West Indian origin.
      METHOD: Case reports. RESULTS: In Case 1 (82-year-old), the disease presented
      when the patient was 50 years old with decreased visual acuity in the right eye.
      Onset of symptoms in the left eye occurred 30 years later. Visual acuity was
      limited to good luminous orientation in both eyes. In Case 2 (78-year-old), the
      disease presented in the right eye when the patient was about 68 years old.
      Visual acuity in the right eye was reduced to good luminous orientation. Symptoms
      in the left eye appeared 10 years later. Visual acuity in the left eye was
      20/100. In both patients, medical history was significant only for arterial
      hypertension. There was no intraocular inflammation or ocular hypertonicity.
      Indocyanine green angiography revealed hyperfluorescent polypoidal dilatations at
      early and intermediate phases, characteristic of PCV. CONCLUSION: These
      observations argue in favor of a genetic component in PCV.

PMID- 25390077
TI  - Phenotype specific association of the TGFBR3 locus with nonsyndromic
      cryptorchidism.
AB  - PURPOSE: Based on a genome-wide association study of testicular dysgenesis
      syndrome showing a possible association with TGFBR3, we analyzed data from a
      larger, phenotypically restricted cryptorchidism population for potential
      replication of this signal. MATERIALS AND METHODS: We excluded samples based on
      strict quality control criteria, leaving 844 cases and 2,718 controls of European
      ancestry that were analyzed in 2 separate groups based on genotyping platform (ie
      Illumina(r) HumanHap550, version 1 or 3, or Human610-Quad, version 1 BeadChip in
      group 1 and Human OmniExpress 12, version 1 BeadChip platform in group 2).
      Analyses included genotype imputation at the TGFBR3 locus, association analysis
      of imputed data with correction for population substructure, subsequent meta
      analysis of data for groups 1 and 2, and selective genotyping of independent
      cases (330) and controls (324) for replication. We also measured Tgfbr3 mRNA
      levels and performed TGFBR3/betaglycan immunostaining in rat fetal gubernaculum.
      RESULTS: We identified suggestive (p <= 1* 10(-4)) association of markers in/near
      TGFBR3, including rs9661103 (OR 1.40; 95% CI 1.20, 1.64; p = 2.71 * 10(-5)) and
      rs10782968 (OR 1.58; 95% CI 1.26, 1.98; p = 9.36 * 10(-5)) in groups 1 and 2,
      respectively. In subgroup analyses we observed strongest association of
      rs17576372 (OR 1.42; 95% CI 1.24, 1.60; p = 1.67 * 10(-4)) with proximal and
      rs11165059 (OR 1.32; 95% CI 1.15, 1.38; p = 9.42 * 10(-4)) with distal testis
      position, signals in strong linkage disequilibrium with rs9661103 and rs10782968,
      respectively. Association of the prior genome-wide association study signal
      (rs12082710) was marginal (OR 1.13; 95% CI 0.99, 1.28; p = 0.09 for group 1), and
      we were unable to replicate signals in our independent cohort. Tgfbr3/betaglycan
      was differentially expressed in wild-type and cryptorchid rat fetal gubernaculum.
      CONCLUSIONS: These data suggest complex or phenotype specific association of
      cryptorchidism with TGFBR3 and the gubernaculum as a potential target of TGFbeta
      signaling.

PMID- 25390078
TI  - Preoperative predictors of pathological lymph node metastasis in patients with
      renal cell carcinoma undergoing retroperitoneal lymph node dissection.
AB  - PURPOSE: Patients with locally advanced renal cell carcinoma represent a subset
      that may benefit from retroperitoneal lymph node dissection. We identified
      preoperative clinical predictors of positive lymph nodes in patients with renal
      cell carcinoma without distant metastasis who underwent retroperitoneal lymph
      node dissection. MATERIALS AND METHODS: We retrospectively analyzed data on a
      consecutive cohort of 1,270 patients with cTany Nany M0 renal cell carcinoma who
      were treated at a single institution from 1993 to 2012. Multivariate analysis was
      performed to determine preoperative predictors of pathologically positive lymph
      nodes in patients who underwent retroperitoneal lymph node dissection. A nomogram
      was developed to predict the probability of lymph node metastasis. Overall,
      cancer specific and recurrence-free survival was estimated using the Kaplan-Meier
      Method. RESULTS: We identified 1,270 patients with renal cell carcinoma without
      distant metastasis who had (564) or did not have (706) retroperitoneal lymph node
      dissection performed. Of the 564 patients 131 (23%) and 433 (77%) had pN1 and pN0
      disease, and 60 (37%) and 29 (7.2%) had cN1pN0 and cN0pN1 disease, respectively.
      ECOG PS, cN stage, local symptoms and lactate dehydrogenase were associated with
      nodal metastasis on multivariable analysis. A nomogram was developed with a C
      index of 0.89 that demonstrated excellent calibration. Differences in overall,
      cancer specific and recurrence-free survival among pNx, pN0 and pN1 cases were
      statistically significant (p <0.001). CONCLUSIONS: Local symptoms, ECOG PS, cN
      stage and lactate dehydrogenase were independent predictors of lymph node
      metastasis in patients who underwent retroperitoneal lymph node dissection. Our
      predictive nomogram using these factors showed excellent discrimination and
      calibration.

PMID- 25390080
TI  - Posterior vitreous cortex characteristics of an eye with asteroid hyalosis.
AB  - PURPOSE: To describe both the clinical and the histological characteristics of
      the vitreoretinal interface of an eye with asteroid hyalosis (AH). METHODS: A 76
      year-old woman presented with a left eye with AH and an epiretinal membrane
      (ERM). Preoperative slit-lamp biomicroscopy revealed anatomical posterior
      vitreous detachment with a Weiss ring. Preoperative best-corrected visual acuity
      (BCVA) was 20/50. The patient underwent triamcinolone acetonide-assisted
      vitrectomy, along with peeling of the internal limiting membrane (ILM). The ERM
      and ILM were removed together with surgical ILM forceps. The excised ILM was
      analyzed with transmission electron microscopy (TEM). We also compared the
      histological characteristics of this tissue with those of tissue from a non-AH
      eye with idiopathic ERM. RESULTS: A massive collagenous matrix with few cellular
      components, suggesting residual posterior vitreous but not ERM, was observed on
      the excised ILM of the AH eye. BCVA improved to 20/25 6 months after surgery. TEM
      of a non-AH eye with idiopathic ERM revealed a cellular rich component and
      extracellular matrix on the ILM. CONCLUSION: We found evidence demonstrating a
      split in the posterior vitreous cortex, representing, to our knowledge, the first
      case report of this phenomenon in an eye with AH.

PMID- 25390081
TI  - Septo-optic dysplasia associated with abnormal foveal development.
AB  - PURPOSE: To report a case of abnormal foveal development in a patient with septo
      optic dysplasia. METHODS: Observational case report, consisting of clinical
      examination, fluorescein angiography, and optical coherence tomographic (OCT)
      evaluation of a patient who presented with septo-optic dysplasia. RESULTS: A 3
      month-old girl with septo-optic dysplasia was found to have bilateral foveal
      schisis by OCT and absence of foveal avascular zone by fluorescein angiography.
      CONCLUSIONS: Abnormal foveal development can be seen in patients with septo-optic
      dysplasia. Both foveal schisis and absence of foveal avascular zone may
      contribute to visual outcome. Detailed macular evaluation is recommended in
      patients who present with optic nerve hypoplasia.

PMID- 25390082
TI  - Bilateral endogenous endophthalmitis due to pseudomonas aeruginosa in a neonate.
AB  - BACKGROUND: Bacterial eye infections are rare in the neonatal population and
      usually come from exogenous spread. Eye infection due to Pseudomonas aeruginosa,
      although uncommon, may be a devastating disease, especially in premature infants.
      METHODS: Retrospective review of the clinical chart of a 10-day-old newborn baby
      with bilateral endogenous Pseudomonas aeruginosa endophthalmitis. RESULTS: The
      patient presented with leukokoria in both eyes 7 days after the onset of severe
      septicemia due to endophthalmitis in both eyes. The baby received systemic
      treatment with meropenem and vancomycin, which the cultured bacteria were
      susceptible to, but the infection progressed. Intravitreal ceftazidime treatment
      and later vitrectomy could not prevent complete retina detachment and the
      progressive evolution to phthisis. CONCLUSION: Aggressive therapy including
      systemic antibiotics, intravitreous antibiotic injection, and vitrectomy could
      not prevent a poor outcome leading to retinal detachment and blindness in both
      eyes. A discussion of the treatment options and a review of the literature are
      also included.

PMID- 25390083
TI  - Acute bilateral peripheral cone system dysfunction.
AB  - PURPOSE: To report electrophysiological and psychophysical findings in an unusual
      case with acute loss of the peripheral visual field bilaterally. METHODS: A 19
      year-old woman underwent fundus photography, fluorescein angiography, visual
      field testing, determination of full-field electroretinograms (ERGs) and
      multifocal ERGs (mfERGs), and rod-cone perimetry in addition to routine
      ophthalmologic examinations. RESULTS: Findings of fundus examination and
      fluorescein angiography were completely normal, and best-corrected visual acuity
      was 1.0 in both eyes. However, static perimetry revealed a temporal field defect
      in the right eye and an arcuate scotoma in the left eye. Full-field ERG cone
      responses were significantly reduced, but rod responses were normal in both eyes.
      Psychophysical rod-cone perimetry demonstrated that the peripheral cone system
      was impaired whereas the rod sensitivity was completely normal. mfERGs showed
      that the local cone responses were well preserved in the central retina but were
      severely reduced in the peripheral retina in both eyes. CONCLUSIONS: These
      results indicate that there is an unusual retinopathy showing acute dysfunction
      of the peripheral cone system bilaterally whereas the rod system is functioning
      normally.

PMID- 25390084
TI  - Retinal tear located beneath the detached internal limiting membrane associated
      with ruptured macroaneurysm.
AB  - BACKGROUND: Rupture of retinal arterial macroaneurysm has a variety of fundus
      features. We report a case of ruptured retinal arterial macroaneurysm appearing
      concomitantly with a retinal tear located beneath the detached internal limiting
      membrane (ILM) that was apparent during vitrectomy. METHODS: Vitrectomy with ILM
      peeling was performed on a 50-year-old man for sub-ILM hemorrhage and subretinal
      hemorrhage caused by ruptured macroaneurysm. RESULTS: After ILM peeling, a
      retinal tear was found within the detached ILM. The sub-retinal hemorrhage was
      aspirated from the retinal tear. The retina was finally reattached. CONCLUSIONS:
      Extensive sub-ILM hemorrhage may cause retinal tear. Careful intraoperative
      examination and treatment are needed.

PMID- 25390085
TI  - Central retinal vein occlusion in a young adult during risperidone therapy.
AB  - BACKGROUND: Various articles in the literature point out the higher risk of
      venous thrombosis in patients taking antipsychotic drugs. However, to our
      knowledge, an association with central retinal vein occlusion (CRVO) has not been
      reported before. METHODS: We describe the clinical and angiographic findings of a
      patient with CRVO that may have been related to his antipsychotic medication.
      RESULTS: A 19-year-old patient had been taking risperidone and fluoxetine for the
      last 7 months. He presented with atypical nonischemic CRVO with atypical deep
      intraretinal hemorrhages, a swollen optic disk, dilatation and engorgement of
      retinal veins, and optic disk capillaries. Despite a detailed workup, no systemic
      or ocular risk factors for a thromboembolic event were found. He had
      hyperprolactinemia resulting from his medication. CONCLUSION: The use of
      risperidone may be a risk factor for CRVO.

PMID- 25390086
TI  - Bilateral diffuse uveal melanocytic proliferation and loss of retinal pigment
      epithelium.
AB  - PURPOSE: To describe a fundus autofluorescent photographic pattern in a case of
      bilateral diffuse uveal melanocytic proliferation (BDUMP) with occult esophageal
      carcinoma. METHODS: Observational case report. RESULTS: Color photography
      captured multiple round areas of discoloration throughout the fundus in a
      background of orange pigmentation that may have represented a lipofuscin-laden
      retinal pigment epithelium (RPE). Autofluorescence photography showed extensive
      nummular areas of hypoautofluorescence interspersed between areas of
      hyperautofluorescence as a result of extensive deposition of lipofuscin within
      the RPE. CONCLUSION: Our case attests to the utility of autofluorescence
      photography as a sensitive, noninvasive imaging modality for the early detection
      of BDUMP.

PMID- 25390087
TI  - What you see is not always what you get in atrophic macular disease.
AB  - PURPOSE: To show that the area of atrophy seen on ophthalmoscopy may not
      correspond with the area of scotoma in some macular diseases. METHODS: Three
      cases are presented, one with geographic atrophy (GA) from age-related macular
      degeneration, one with Stargardt disease, and one with a macular dystrophy. Nidek
      MP-1 microperimetry was performed and the correspondence of the dense scotoma to
      the visible atrophy is reported. RESULTS: In the GA patient, the dense scotoma
      corresponds with the atrophy. In the patient with Stargardt disease, the dense
      scotoma is larger than the area of visible atrophy. In the patient with a macular
      dystrophy, the dense scotoma is smaller than the area of visible atrophy.
      CONCLUSIONS: In GA from age-related macular degeneration, the dense scotoma
      generally corresponds with the atrophy, so that measurement of the enlargement
      rate of the atrophy is a direct measure of enlargement of the scotoma. This may
      not be true of other macular diseases.

PMID- 25390088
TI  - Acute posterior multifocal placoid pigment epitheliopathy and thalamic
      infarction.
AB  - OBJECTIVES: To report a patient with acute posterior multifocal placoid pigment
      epitheliopathy (APMPPE) who developed a thalamic infarction and to discuss this
      unusual presentation. DESIGN: Interventional case report and literature review.
      METHODS: A 23-year-old man with APMPPE presented with acute confusion and memory
      loss. He underwent complete ophthalmologic and neurologic examination, with
      neuroimaging including magnetic resonance angiography (MRA). MAIN OUTCOME
      MEASURES: Clinical course and angiographic findings. RESULTS: Magnetic resonance
      imaging (MRI) showed a left posteromedial thalamic infarction, with a
      corresponding filling defect of the left posterior communicating artery
      demonstrated by MRA. The patient underwent further treatment with intravenous
      corticosteroids followed by continued oral therapy with taper over several weeks.
      CONCLUSION: Although the association of APMPPE and cerebral vasculitis has been
      described, this patient is unique due to the subtle clinical presentation and
      anatomic location. This case emphasizes the importance of appropriate counseling
      of patients with APMPPE, as well as prompt recognition of clinical symptoms to
      enable timely intervention and treatment.

PMID- 25390089
TI  - Subretinal Candida albicans abscesses responsive to oral voriconazole.
AB  - PURPOSE: To report findings in a patient with bilateral Candida albicans
      subretinal abscesses responsive to oral voriconazole. METHODS: Retrospective,
      case report. RESULTS: A 62-year-old woman presented with bilateral C albicans
      subretinal abscesses secondary to chronic immunosuppression. The abscesses
      responded to oral voriconazole and resolved completely within 4 months of initial
      presentation. CONCLUSIONS: This case illustrates that oral voriconazole may be
      effective in the treatment of large subretinal abscesses in an immunocompromised
      patient. Additionally, this report suggests that a subretinal aspirate may have
      greater diagnostic sensitivity than a vitreous specimen in eyes with infectious
      subretinal abscesses.

PMID- 25390090
TI  - Focal laser photocoagulation for polypoidal choroidal vasculopathy associated
      with choroidal nevus.
AB  - PURPOSE: To describe a patient treated with focal laser photocoagulation for
      polypoidal choroidal vasculopathy (PCV) secondary to choroidal nevus. METHODS: A
      62-year-old woman presented with PCV secondary to choroidal nevus in the right
      eye and best-corrected visual acuity of 20/100. The polypoidal lesions were
      treated with focal laser photocoagulation and clinical and instrumental data were
      prospectively analyzed. RESULTS: Three months after focal laser photocoagulation,
      fluorescein angiography showed no leakage from the polypoidal lesions, optical
      coherence tomography scans displayed absence of subretinal fluid, and visual
      acuity improved to 20/25 and remained stable throughout an 18-month follow-up.
      CONCLUSION: Focal laser photocoagulation seems to be an effective and safe
      treatment for PCV secondary to choroidal nevus.

PMID- 25390091
TI  - Successful treatment of a serous retinal pigment epithelial detachment by coiling
      of a carotid-cavernous fistula.
AB  - PURPOSE: To report a patient presenting with a symptomatic retinal pigment
      epithelial detachment (RPED) that resolved after successful treatment of a slow
      flow dural carotid cavernous fistula (CCF). Possible pathophysiological
      mechanisms are discussed. METHODS: Interventional case report. RESULTS: A 69-year
      old female presented with left uniocular distortion, confirmed on fluorescein and
      indocyanine green angiography to be secondary to a non-vascularised serous RPED.
      Further examination revealed a long standing left VI nerve palsy, mild proptosis
      and conjunctival injection. Magnetic resonance and cranial angiography confirmed
      the presence of a dural CCF. Surgical closure of the CCF resulted in a rapid
      resolution of the clinical signs and improvement in visual symptoms. CONCLUSIONS:
      Patients with serous RPED and other signs or symptoms of a CCF may warrant
      neuroimaging of the orbit and/or angiography to evaluate for CCF, as correct
      diagnosis may lead to an excellent visual outcome.

PMID- 25390092
TI  - Diffuse infiltrating anterior retinoblastoma in a 16-year-old boy.
AB  - PURPOSE: To report an anterior diffuse infiltrating retinoblastoma in a teenager
      with a positive titer for toxocariasis. METHODS: Clinical evaluation, enucleation
      and description of pathology. RESULTS: The patient had a relatively flat, white
      lesion near the equator of the globe, with tumor seeding in the ciliary body,
      zonule and in the anterior chamber. Diffuse infiltrating retinoblastoma was
      suspected clinically and confirmed histopathologically after enucleation.
      CONCLUSION: Retinoblastoma can occur in a teenager who has a positive toxocara
      titer. The characteristic features should suggest the diagnosis of
      retinoblastoma, despite the patient's age.

PMID- 25390093
TI  - SPONTANEOUS RESOLUTION OF A STAGE 3 MACULAR HOLE: Long-Term Follow-up With
      Optical Coherence Tomography.
AB  - BACKGROUND: While spontaneous resolution of idiopathic macular holes is well
      documented for early macular holes, spontaneous closure of full-thickness macular
      holes has been less frequently reported. METHODS: We followed a case of an
      idiopathic full-thickness stage III macular hole and its course of spontaneous
      closure using optical coherence tomography (OCT 3, Carl Zeiss Meditec, CA) over a
      2-year period. RESULTS: OCT scans demonstrated evidence of spontaneous closure of
      the macular hole over the 2-year follow-up period. Bridging of glial tissue over
      the macular hole area appeared to occur first with successive scans showing a
      decrease in the size of the hole. To our knowledge, this is the longest follow-up
      with OCT in a case of spontaneous resolution of macular holes that has been
      reported. CONCLUSION: Recognition of the likelihood of spontaneous closure of
      macular holes has important clinical values. The advent of OCT technology has
      provided significant capabilities in the diagnosis and monitoring of macular
      holes; it has also contributed to the greater understanding of the potential
      mechanisms involved in spontaneous macular hole closure.

PMID- 25390094
TI  - Sterile endophthalmitis following intravitreal injection of preservative-free
      triamcinolone acetonide.
AB  - PURPOSE: To describe two cases of sterile endophthalmitis following intravitreal
      injection of preservative-free triamcinolone acetonide. METHODS: Chart review.
      RESULTS: Two patients with histories of sterile inflammatory reaction to
      intravitreal Kenalog (triamcinolone acetonide) subsequently were treated with
      intravitreal injections of preservative-free triamcinolone. Both patients
      presented 2 to 3 days after injection with significant anterior chamber cell
      reaction without pain or inflammation-related conjunctival injection. The
      intraocular inflammation of both patients resolved completely using only topical
      steroids and antibiotics. CONCLUSIONS: An inflammatory reaction to the vehicle
      has been the leading hypothesis for the etiology of the sterile inflammatory
      response following intravitreal Kenalog injections. The use of preservative-free
      triamcinolone is intended to eliminate this potential source of toxicity. These
      cases demonstrate that noninfectious endophthalmitis can develop even with
      preservative-free triamcinolone.

PMID- 25390095
TI  - Fundus autofluorescence in choroidal rupture.
AB  - PURPOSE: To investigate fundus autofluorescence (FAF) imaging findings for
      patients with choroidal rupture. METHODS: FAF images were recorded with a new
      generation confocal scanning laser ophthalmoscope. Three patients with choroid
      ruptures, one acute and two chronic, were included in the study. RESULTS:
      Choroidal ruptures typically appeared as hypoautofluorescent crescent-shaped
      lesions on FAF images. In the case of acute choroid rupture, the whole extent of
      the rupture was clearly seen, and visibility of the lesion was found to be better
      by FAF imaging than by ophthalmoscopy and fundus fluorescein angiography.
      CONCLUSION: Choroidal rupture has a typical appearance by FAF imaging. FAF
      imaging may be a useful noninvasive tool in the recognition of these lesions
      early in their course.

PMID- 25390096
TI  - Short-term intraocular pressure trends after intravitreal injection of
      bevacizumab (avastin).
AB  - PURPOSE: To report the changes in intraocular pressure (IOP) after intravitreal
      injection of bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA).
      DESIGN: Retrospective chart review. METHODS: After the charts of 29 patients who
      underwent 51 consecutive intravitreal injections of bevacizumab were reviewed,
      analysis of the short-term effect of bevacizumab injections on IOP was performed.
      RESULTS: Mean baseline IOP +/- SD was 15.1 +/- 2.35 mm Hg (range, 10-22 mm Hg).
      Mean postinjection IOP +/- SD was 20.1 +/- 4.70 mm Hg (range, 16-31 mm Hg). Mean
      change in IOP from baseline to ~30 minutes after bevacizumab injection was 5.0 mm
      Hg (P = 0.0027). Mean IOP +/- SD at the first follow-up visit, which occurred ~25
      days (range, 5-43 days) after injection, was 14.7 +/- 2.93 mm Hg (range, 10-20 mm
      Hg). CONCLUSIONS: Intravitreal injection of bevacizumab seems to be safe from an
      IOP standpoint in the short term. IOP monitoring immediately after injection may
      not be necessary.

PMID- 25390097
TI  - Intravitreal bevacizumab in the management of posttraumatic choroidal neovascular
      membrane.
AB  - PURPOSE: To report the therapeutic response in the treatment of juxtafoveal
      choroidal neovascular membrane (CNVM) secondary to traumatic choroidal rupture
      with intravitreal bevacizumab. METHODS: A 20-year-old man presented with
      distortion of central vision following blunt trauma and was found to have
      juxtafoveal, classic CNVM associated with a choroidal rupture. The patient
      underwent intravitreal bevacizumab (1.25 mg/0.05 mL) and was periodically
      followed up. RESULTS: Four weeks post injection, best-corrected visual acuity
      improved to 20/20. Optical coherence tomography revealed regression of CNVM and
      resolution of subretinal fluid. The anatomic and functional status of the treated
      eye was maintained at 6 months follow-up. No treatment-related ocular or systemic
      adverse effects were noted. CONCLUSION: Bevacizumab appears to be safe and
      effective in the treatment of CNVM secondary to choroidal rupture.

PMID- 25390098
TI  - Bifocal malignant melanoma of the choroid in a 1.5-year-old child.
AB  - PURPOSE: To report a case of bifocal malignant melanoma of the choroid in a 1.5
      year-old child. METHOD: Case report. RESULTS: Fundus examination showed bifocal
      malignant melanoma of the choroid with secondary retinal detachment.
      Histopathology confirmed malignant melanoma of the choroid, mixed cell type.
      CONCLUSION: Malignant melanoma in an infant, though rare, should be kept in mind
      in differential diagnosis of pigmented intraocular mass.

PMID- 25390099
TI  - Post-cataract surgery cystoid macular edema from choriocapillaris submacular
      leakage in a patient with crohn disease: a case report.
AB  - PURPOSE: To describe an unusual case of cystoid macular edema after cataract
      surgery in a patient with Crohn disease. METHODS: A confocal scanning laser
      ophthalmoscopic study was performed on one eye before and after systemic
      corticosteroid treatment. Both fluorescein and indocyanine green angiograms were
      used to visualize vascular leakage. RESULTS: Both fluorescein and indocyanine
      green angiograms indicated early-phase leakage in the macular region. The early
      phase indocyanine green leakage was from choroidal vasculature and suggested
      choriocapillaris vasculitis. In the later phases, the fluorescein angiogram
      showed the typical petaloid pattern of cystoid macular edema. After 1 month of
      treatment, the abnormal indocyanine green leakage disappeared with a concomitant
      increase in visual acuity. CONCLUSIONS: We report possible choriocapillaritis
      associated with Crohn disease based on dynamic angiography that revealed
      indocyanine green leakage in combination with early-phase fluorescein leakage. To
      our knowledge, this is the first description of choriocapillaris vasculitis
      associated with Crohn disease.

PMID- 25390100
TI  - Wound leak after intravitreal injection of bevacizumab.
AB  - PURPOSE: To report an occurrence of wound leak from the injection site after
      intravitreal injection of bevacizumab. A possible underlying etiology is
      discussed. METHODS: A single injection of bevacizumab was given for treatment of
      choroidal neovascularization complicating previous choroidal rupture. RESULTS: A
      reduction in vision and hypotony were noted 1 day after injection. With
      conservative management, there was spontaneous resolution of the wound leak.
      CONCLUSION: The risk of wound leak after intravitreal injection may be higher for
      younger patients and those who have undergone vitrectomy. All patients and
      clinicians, however, should be alert to vision decline after injection, and
      prompt evaluation should be performed to ascertain the cause. For patients with
      persistent wound leak, surgical intervention may be required.

PMID- 25390101
TI  - Incidence of noninfectious endophthalmitis after intravitreal injection of
      preservative-free triamcinolone acetonide.
AB  - PURPOSE: To determine the incidence of noninfectious inflammatory endophthalmitis
      after preservative-free intravitreal triamcinolone acetonide (PF-IVTA) injection.
      PATIENTS AND METHODS: We performed a retrospective interventional case series,
      reviewing the medical records of all patients receiving PF-IVTA injection from
      July 1, 2006, through December 31, 2006; 444 patients were identified who
      received a total of 502 PF-IVTA injections. Demographic information and details
      of postinjection inflammation or endophthalmitis were collected. RESULTS: Eleven
      eyes (2.2%) of 11 patients (2.5%) had an inflammatory reaction after PF-IVTA
      injection. Complete obscuration of all fundus details was observed in seven eyes,
      while moderate inflammation was noted in four eyes. An inflammatory hypopyon,
      thought not to represent particles of triamcinolone, was seen in eight eyes. The
      indication for IVTA injection was cystoid macular edema in seven eyes.
      CONCLUSIONS: Postinjection inflammatory reactions are not uncommon after PF-IVTA
      injection. Noninfectious endophthalmitis after IVTA injection appears to be more
      common in eyes being treated for cystoid macular edema.

PMID- 25390102
TI  - Ranibizumab for choroidal neovascularization in fundus flavimaculatus.
AB  - PURPOSE: To report the features of a case with late-onset fundus flavimaculatus
      (FFM) complicated by choroidal neovascularization (CNV) and treated with
      ranibizumab. METHODS: Retrospective interventional case report. PATIENT: A 51
      year-old woman presented with right eye decreased vision. Fundus flavimaculatus
      with CNV was diagnosed by electroretinography and fluorescein angiography.
      RESULTS: Two intravitreal injections of ranibizumab were needed for the
      treatment. At the end of follow-up (9 months) no leakage was observed and visual
      acuity improved. CONCLUSION: Choroidal neovascularization is a rare complication
      of FFM. Ranibizumab, an anti-VEFG drug, stopped neovascularization and improved
      final visual acuity in this case, so it must be considered in the treatment of
      CNV in late onset FFM.

PMID- 25390103
TI  - Intraocular bevacizumab for iris neovascularization in a silicone oil-filled eye.
AB  - PURPOSE: To report the effectiveness of intravitreal injection of bevacizumab for
      treatment of iris neovascularization in a silicone oil-filled eye. DESIGN: Case
      report. PATIENT: A 56-year-old man with recurrent retinal detachment associated
      with iris neovascularization. RESULTS: Iris neovascularization regressed after
      treatment with a 1.25-mg intravitreal injection of bevacizumab in the presence of
      silicone oil. DISCUSSION: Intraocular injection of bevacizumab is an effective
      short-term treatment of neovascularization caused by persistent retinal
      detachment even in the presence of silicone oil. The standard dose of 1.25 mg of
      bevacizumab may not require adjustment in an aphakic vitrectomized eye.

PMID- 25390104
TI  - Malignant transformation of retinocytoma into retinoblastoma.
AB  - PURPOSE: To describe presumed malignant transformation of a single retinocytoma
      into retinoblastoma in a child with multifocal retinocytomas. METHODS: A 7-year
      old boy presented with a white fundus lesion in the left eye. Ophthalmic
      evaluation showed one retinocytoma (spontaneously regressed
      retinoblastoma/arrested retinoblastoma) in each eye and one active endophytic
      retinoblastoma in the left eye. The left eye was enucleated. RESULTS:
      Histopathologic examination disclosed a small predominantly endophytic
      retinoblastoma with extensive vitreous seeding in association with a basal focus
      of well differentiated tumor with photoreceptor differentiation, suggestive of
      retinocytoma. The findings were consistent with malignant transformation of
      retinocytoma into retinoblastoma. CONCLUSION: Patients presumed to have
      retinocytoma at clinical evaluation should have lifelong follow-up for the remote
      possibility of malignant transformation.

PMID- 25390105
TI  - Hemorrhagic recurrence of neovascular age-related macular degeneration not
      predicted by spectral domain optical coherence tomography.
AB  - PURPOSE: To report a case in which a patient with neovascular age-related macular
      degeneration developed a large submacular hemorrhage 2 days after spectral domain
      optical coherence tomography imaging, which revealed no intra- or subretinal
      fluid. METHODS: A noninterventional case report. RESULTS: A 93-year-old woman
      with neovascular age-related macular degeneration was seen for a regular follow
      up examination 3 years after treatment with verteporfin photodynamic therapy in
      which lesion quiescence was achieved. Visual acuity was stable at 20/200, and
      spectral domain optical coherence tomography scans using 2 different instruments
      revealed no intra- or subretinal fluid. Two days after clinical examination and
      imaging, the patient presented with a large submacular hemorrhage and 5/400
      vision. CONCLUSION: Hemorrhagic exudation from choroidal neovascularization in
      age-related macular degeneration may occur suddenly, even in the absence of fluid
      detected by spectral domain optical coherence tomography.

PMID- 25390106
TI  - Radiation maculopathy complicated by intraretinal neovascularization treated with
      intravitreal bevacizumab.
AB  - PURPOSE: The purpose of this study was to describe a case of radiation
      maculopathy as a result of intraretinal neovascularization, treated with
      intravitreal bevacizumab. METHODS: This is an interventional case report. A 51
      year-old man was treated with radiotherapy and chemotherapy for nasopharyngeal
      carcinoma. He developed radiation maculopathy associated with intraretinal
      neovascularization in the left eye. He underwent a course of 3 intravitreal
      injections of bevacizumab (1.25 mg/0.05 mL). RESULTS: The visual acuity in the
      left eye improved with complete closure of the intraretinal neovascularization
      and no recurrence 17 months after the last bevacizumab injection. CONCLUSION:
      This case of radiation-induced intraretinal neovascularization responded well to
      bevacizumab treatment. These lesions may respond more favorably if treated
      earlier.

PMID- 25390107
TI  - Chaetomium retinitis.
AB  - PURPOSE: To report a case of Chaetomium atrobrunneum retinitis in a patient with
      Hodgkin lymphoma. METHODS: We studied the ocular manifestations of an 11-year-old
      boy with retinitis. Biomicroscopy, ophthalmoscopy, and fundus photography were
      done. Magnetic resonance imaging of the brain was performed. A vitreous biopsy
      was subjected to viral, bacterial, and fungal cultures. RESULTS: Vitreous culture
      grew C. atrobrunneum. Magnetic resonance imaging showed multiple cerebral lesions
      consistent with an infectious process. The patient was given intravenous
      voriconazole and showed improvement of the ocular and central nervous system
      lesions. CONCLUSION: We report a case of central nervous system and ocular
      lesions by C. atrobrunneum. The retinitis was initially misdiagnosed as
      cytomegaloviral retinitis. Vitreous biopsy helped in the early diagnosis and
      prompt treatment of a life- and vision-threatening infection.

PMID- 25390108
TI  - Recurrent pseudomonas aeruginosa endophthalmitis.
AB  - PURPOSE: To report a case of recurrent endophthalmitis resulting from Pseudomonas
      aeruginosa requiring removal of the intraocular lens and lens capsule to
      eradicate the infection. METHODS: Evaluation for management of presumed
      endophthalmitis after uneventful cataract surgery with intraocular lens
      implantation. RESULTS: Eventual resolution of P. aeruginosa intraocular infection
      after pars plana vitrectomy 3 times and removal of the intraocular lens and lens
      capsule with final visual acuity of 20/30. CONCLUSION: P. aeruginosa is an
      aggressive organism that often presents in a fulminant manner, requiring
      vitrectomy and repeated injections of intravitreal antibiotics. Rarely, the
      organism can be harbored in the lens capsule, requiring intraocular lens
      explantation and capsule removal for complete eradication and best visual
      recovery.

PMID- 25390109
TI  - Bilateral simultaneous endogenous Aspergillus endophthalmitis in an
      immunocompetent patient.
AB  - PURPOSE: To report a case of bilateral endogenous Aspergillus endophthalmitis in
      an immunocompetent patient. METHODS: We report a young immunocompetent 26-year
      old Indian woman who presented with bilateral simultaneous endogenous
      endophthalmitis and was managed with pars plana vitreous surgery in both the
      eyes. RESULTS: Smear examination of the vitrectomy specimen from the left eye
      identified septate hyphae with acute-angle branching, which on culture showed
      growth of Aspergillus fumigatus. A detailed systemic evaluation failed to reveal
      any systemic focus or predisposing factor for fungal infection. The patient had
      received an intravenous dextrose infusion 2 weeks before this episode while being
      treated at a rural hospital for malarial infection. During follow-up, she
      developed bilateral rhegmatogenous retinal detachment requiring revised pars
      plana vitreous surgery with silicon oil tamponade. CONCLUSION: An immunocompetent
      patient can present with bilateral simultaneous endogenous Aspergillus
      endophthalmitis after receiving an intravenous infusion of presumably
      contaminated dextrose solution.

PMID- 25390110
TI  - Control of disseminated scedosporium prolificans infection and endophthalmitis.
AB  - PURPOSE: To report a case of endogenous endophthalmitis as the presenting sign of
      a disseminated Scedosporium prolificans infection. METHODS: A 38-year-old woman
      on chronic immunosuppressive treatment for a cardiac transplant was examined for
      blurry vision in her right eye. Dilated fundus examination in the right eye
      revealed a large serous retinal detachment with subretinal cream-colored masses.
      RESULTS: Complete pars plana vitrectomy with vitreal biopsies was performed and
      revealed S. prolificans on culture. Multiple intravitreal voriconazole injections
      as well as systemic voriconazole and terbinafine resulted in control and
      suppression of both the ocular and systemic disease. CONCLUSION: Scedosporium
      prolificans endogenous endophthalmitis represents a difficult to treat
      opportunistic infection in immunocompromised patients. However, newer-generation
      antifungals offer the potential for suppression of systemic disease and the
      possibility of avoiding enucleation in the setting of endophthalmitis.

PMID- 25390111
TI  - Postsurgical bacterial endophthalmitis presenting as frosted branch angiitis: a
      case report.
AB  - PURPOSE: To report a case of unilateral postsurgical bacterial endophthalmitis,
      which presented in an unusual manner with frosted branch angiitis. METHODS: We
      reviewed the chart of a patient with acute postoperative bacterial
      endophthalmitis who presented initially as frosted branch angiitis and
      subsequently developed full-fledged endophthalmitis. RESULTS: The patient was
      treated with conventional treatment for postsurgical endophthalmitis along with
      oral steroids. He recovered full vision with complete resolution of the frosted
      branch appearance as well as the endophthalmitis. DISCUSSION: Primary frosted
      branch angiitis is a rare form of vasculitis seen in otherwise healthy young
      children. It has also been reported secondary to autoimmune disorders,
      malignancies such as lymphoma, and various infective agents. Commonly associated
      infective agents are viruses such as cytomegalovirus, herpes simplex, varicella
      zoster, and human immunodeficiency virus. There are isolated case reports of
      associated rubella and toxoplasma infections. One case has been reported in
      association with endogenous Fusarium endophthalmitis. No case has been reported
      in association with bacterial endophthalmitis.

PMID- 25390112
TI  - Bilateral circumferential macular folds in inflicted childhood neurotrauma.
AB  - PURPOSE: To report an infant with inflicted neurotrauma who exhibited bilateral
      circumferential macular folds. METHODS: Bedside ophthalmic examination and fundus
      photography using RetCam-II (Clarity Medical Systems, Pleasanton, CA). RESULTS:
      Both pupils were miotic and nonreactive. External and anterior segments showed no
      abnormality. The fundus showed bilateral diffuse multilaminar retinal,
      subhyaloid, and vitreous hemorrhages. Distinctive macular folds were noted
      bilaterally. CONCLUSION: Circumferential macular folds are most commonly found in
      abused infants, although it has been suggested that they may be associated with
      Terson syndrome and severe crush injury.

PMID- 25390113
TI  - Progression of traumatic lamellar macular hole to full-thickness macular hole and
      retinal detachment in a 3-year-old child.
AB  - BACKGROUND: Traumatic macular holes in children are uncommon, and retinal
      detachment from a macular hole is even more uncommon because the vitreous is
      formed. METHODS: Interventional case report. RESULTS: A 3-year-old boy presented
      after trauma with a lamellar macular hole in his left eye. Over the next month,
      progression to a full-thickness macular hole with epiretinal membrane and then
      subsequent retinal detachment was documented with high-resolution optical
      coherence tomography. The patient underwent a pars plana vitrectomy, membrane
      peel, and perfluoropropane tamponade. Six months after surgery, the hole remained
      anatomically closed, and visual acuity was 20/20. CONCLUSION: Retinal detachment
      after a traumatic macular hole in this child was because of hyaloidal traction
      and epiretinal membrane contraction. Pars plana vitrectomy with surgical peeling
      of the epiretinal membrane and internal limiting membrane enabled the macular
      hole to close and the retina to reattach.

PMID- 25390114
TI  - Cat-scratch disease associated with branch retinal artery occlusion.
AB  - PURPOSE: We describe two cases of branch retinal artery occlusion (BRAO) as the
      presenting sign of cat-scratch disease. METHODS AND PATIENTS: Case 1 (25-year-old
      man) presented with decreased vision, visual field changes, a swollen disk, and
      BRAO. Case 2 (27-year-old woman) presented with decreased vision bilaterally:
      findings on examination were a macular star figure on the right eye and a BRAO on
      the left. RESULTS: Both cases clinically improved after a course of systemic
      antibiotics. Case 1 had a normal optic disk and almost a complete resolution of
      the ischemic area 4 weeks after treatment. Case 2 had a complete resolution of
      the BRAO, and her macular exudates and optic disk edema partially resolved 5
      weeks after treatment. CONCLUSION: Cat-scratch disease should be considered in
      the differential diagnosis of BRAO, especially in young patients. The use of
      systemic antibiotics in cat scratch neuroretinitis, although proven beneficial in
      our patients, remains controversial and should probably be reserved for the more
      severe forms of the disease.

PMID- 25390115
TI  - Bilateral arteritis with cytomegalovirus retinitis in a patient infected with
      human immunodeficiency virus.
AB  - PURPOSE: To report an interesting ocular finding and course of bilateral
      arteritis with cytomegalovirus retinitis in a patient infected with the human
      immunodeficiency virus (HIV). METHODS: Retrospective single case report. RESULTS:
      A 39-year-old HIV-positive man on highly active antiretroviral therapy presented
      with a history of diminution of vision in both eyes of 1-month duration. Fundus
      examination showed vitritis, sheathing, and a cordlike appearance of the arteries
      with veins unaffected in both eyes. A patch of cystomegalovirus retinitis was
      noted temporally in the right eye. Fluorescein angiography showed gross areas of
      capillary nonperfusion in both eyes. Polymerase chain reaction of the aqueous tap
      was positive for cytomegalovirus in both eyes. Despite aggressive treatment with
      intravitreal ganciclovir followed by a course of intravenous ganciclovir, the
      right eye progressed to neovascularization, vitreous hemorrhage, neovascular
      glaucoma, and no perception of light. Segmentation and recanalization of arteries
      were noted in the left eye. Immune recovery uveitis developed in the left eye
      after 2 months and was treated with oral steroids and intravenous ganciclovir
      followed by a maintenance dose of valganciclovir. At 3 years follow up, his
      vision and ocular condition in the left eye is stable. CONCLUSION: An interesting
      finding of bilateral arteritis with cystomegalovirus retinitis in an HIV-positive
      patient is reported. The arteritis did not respond very well to intravitreal
      ganciclovir and required a course of intravenous ganciclovir. Early treatment
      with intravenous ganciclovir and laser photocoagulation in such cases may reduce
      visual morbidity.

PMID- 25390116
TI  - Retinitis pigmentosa and punctate cataracts in mevalonic aciduria.
AB  - BACKGROUND: Mevalonic aciduria, caused by deficiency of mevalonate kinase, was
      the first recognized defect in the biosynthesis of cholesterol and isoprenoids.
      Ophthalmic features of this potentially blinding disorder include blue sclera,
      cataract, uveitis, optic atrophy, and, importantly, a retinitis pigmentosa-like
      retinopathy. To date, ~30 cases of this rare autosomal recessive disorder have
      been reported, with no full characterization appearing in the ophthalmic
      literature. METHODS: An 11-year-old white girl with mevalonic aciduria presented
      with decreasing peripheral vision and night blindness. RESULTS: Examination
      revealed decreased central vision, punctate cataracts, and a retinitis pigmentosa
      like retinopathy. Goldmann visual fields confirmed severe constriction in both
      eyes. A full-field electroretinogram was performed. A-waves, B-waves, and
      oscillatory potentials were all nonrecordable in both eyes, indicating severe
      bilateral retinopathy, affecting both cone- and rod-mediated responses. Dark
      adaptation testing showed severely impaired cone and rod function under dark
      adapted (scotopic) conditions. Farnsworth-Munsell hue discrimination (FM-100 hue)
      testing was abnormal in both eyes. CONCLUSION: The ocular findings in patients
      with mevalonic aciduria are heterogeneous and include blue sclerae, cataracts,
      uveitis, retinopathy, and optic atrophy. Visual prognosis is guarded; several
      patients surviving to adulthood have progressed to apparent legal blindness
      caused by cataracts and/or retinopathy.

PMID- 25390117
TI  - Premature closure of inner retinal fenestration in the treatment of optic disk
      pit maculopathy.
AB  - PURPOSE: To describe the results of inner retinal fenestration surgery in a
      patient with chronic macular detachment secondary to an optic disk pit. METHODS:
      A 55-year-old woman had a chronic macular detachment secondary to an optic disk
      pit that was refractory to vitrectomy and laser photocoagulation. A partial
      thickness retinal fenestration that connected the schisis-like retinal cavity to
      the vitreous space was created surgically. RESULTS: One day after surgery, the
      fenestration was shown to be patent by optical coherence tomography (OCT).
      However, 3 weeks postoperatively, the OCT revealed a closed fenestration and
      persistent macular detachment. CONCLUSION: A surgically created inner retinal
      fenestration can close within 3 weeks of surgery without resolution of the
      macular detachment associated with an optic disk pit.

PMID- 25390118
TI  - Drug-induced tubulointerstitial nephritis and uveitis syndrome with posterior
      uveitis resembling acute posterior multifocal placoid pigment epitheliopathy.
AB  - PURPOSE: To report the occurrence of acute posterior multifocal placoid pigment
      epitheliopathy (APMPPE)-like posterior uveitis as part of the ocular
      manifestation of tubulointerstitial nephritis and uveitis (TINU) syndrome.
      METHODS: A 54-year-old previously healthy woman received oral ibuprofen and
      dipirone because of high fever and malaise. Three days after being started on
      this treatment, she developed bilateral posterior uveitis resembling APMPPE
      accompanied by anterior segment inflammation in the context of acute renal
      nephritis and maculopapular skin rash probably related to drug exposure. RESULTS:
      The patient was hospitalized because of acute renal failure and received support
      therapy and topical steroids in both eyes. A renal biopsy was not performed
      (based on good clinical response), but she fulfilled the clinical criteria of
      acute interstitial nephritis and TINU. Although her renal and ocular functions
      improved in the first week, she needed to be readmitted days later because of
      fever and generalized edema and received steroid pulse therapy. Fluorescein
      angiography was consistent with an APMPPE-like pattern and optical coherence
      tomography showed neither macular edema nor subretinal fluid. The ocular picture
      improved during the following weeks with fundus changes resembling those of
      APMPPE. CONCLUSION: Although anterior uveitis is considered the typical ocular
      component of TINU syndrome, posterior uveitis resembling APMPPE may also be its
      ocular manifestation.

PMID- 25390119
TI  - A neovascularized epiretinal membrane in a patient with terson syndrome.
AB  - PURPOSE: We report on a patient with Terson syndrome in the left eye complicated
      by a neovascularized epiretinal membrane likely secondary to cocaine use.
      METHODS: Case report and literature review using the Medline database (1966
      2007). RESULTS: A woman known for cocaine use was seen in the ophthalmology
      clinic for Terson syndrome in the left eye after subarachnoid hemorrhage. Ten
      months later, a neovascularized epiretinal membrane was noted in the left eye and
      confirmed with retinal angiography and optical coherence tomography. After
      vitrectomy, the neovascular membrane was sent for histopathological examination,
      revealing neovascular capillaries. CONCLUSION: Neovascularized epiretinal
      membranes have never been reported in Terson syndrome and in our patient this
      likely occurred due to an ischemic retinal environment created by cocaine use and
      decreased retinal perfusion after subarachnoid hemorrhage.

PMID- 25390120
TI  - Effect of ocular contusion in a patient with chronic central serous
      chorioretinopathy.
AB  - PURPOSE: We report the effect of ocular contusion in a patient with chronic
      central serous chorioretinopathy and posterior cystoid retinal degeneration.
      METHODS: A 56-year-old man who being followed for recurrent-chronic central
      serous chorioretinopathy presented with blurred vision in the left eye 6 days
      after contusion of the eye by a soccer ball. Previously, the left eye had
      received multiple laser treatments in the papillomacular region resulting in a
      large chorioretinal scar. Photodynamic therapy also had been performed in the
      chronic phase of the disease. Optical coherence tomography 2 months before the
      trauma showed cystoid retinal changes at the site of the laser scar and no fluid
      in the fovea. RESULTS: When the left eye was examined after the contusion, visual
      acuity was 20/40. Funduscopic examination did not show retinal opacities. Optical
      coherence tomography revealed cystoid intraretinal cavities and retinal
      detachment that extended from the scar to the fovea. Indocyanine green
      angiography showed choriocapillaris hyperpermeability at the posterior pole that
      was not present at previous examinations. The retinal detachment resolved in 1
      month whereas the new cystoid retinal changes disappeared over the course of 8
      months. Visual acuity returned to the baseline value of 20/26. CONCLUSION: This
      case shows that a contusion injury of the eye can produce a temporary pattern of
      macular exudation with worsening of posterior cystoid retinal degeneration in
      chronic chorioretinopathy. Findings observed in this patient support the concept
      that chorioretinal adherence at the site of a laser scar may have a critical role
      in the development of posterior cystoid retinal degeneration in central serous
      chorioretinopathy.

PMID- 25390121
TI  - Acute retinal necrosis after corticosteroid pulse therapy for unilateral vogt
      koyanagi-harada disease.
AB  - PURPOSE: To report on a patient with unilateral Vogt-Koyanagi-Harada (VKH)
      disease who developed varicella zoster-associated acute retinal necrosis after
      corticosteroid pulse therapy for the VKH disease. METHODS: Observational case
      report. RESULTS: A 36-year-old Japanese man was diagnosed with incomplete VKH
      disease despite having only unilateral changes. After corticosteroid pulse
      therapy, the same eye developed acute retinal necrosis. Polymerase chain reaction
      of an aqueous humor specimen showed DNA of the varicella zoster virus. Seven days
      after intravenous acyclovir, the retinitis disappeared. CONCLUSION: We
      encountered a rare case of unilateral VKH disease that developed acute retinal
      necrosis during corticosteroid pulse therapy. Acute retinal necrosis can develop
      during corticosteroid pulse therapy for VKH disease.

PMID- 25390122
TI  - Functional and morphological evaluation of purtscher retinopathy.
AB  - PURPOSE: To determine the extent of retinal damage in Purtscher retinopathy (PR).
      METHODS: A longitudinal analysis of the retinal morphology and function was made
      by optical coherence tomography and electroretinography, respectively, on a
      patient with unilateral PR. RESULTS: Optical coherence tomography showed a marked
      thickening of the inner retinal layers in the acute phase and a thinning of the
      inner retinal layers and alteration of the outer layers in the chronic phase. The
      site of these changes corresponded with the cotton-wool patches. The results of
      electroretinography indicated reduced inner layer function in the acute phase and
      partial recovery in the chronic phase. CONCLUSION: The inner and outer retinal
      layers are altered morphologically and functionally in eyes with PR. The dynamic
      evaluation on retinal morphology and function may be useful in understanding the
      pathophysiology of PR.

PMID- 25390123
TI  - Required reduction in dose of chemotherapy for retinoblastoma due to down
      syndrome-associated chemosensitivity.
AB  - PURPOSE: To report a case of a boy with bilateral germinal retinoblastoma and
      Down syndrome who was successfully treated despite a predilection toward
      chemotoxicity associated with Down syndrome. METHODS: A 3-month-old boy
      presenting with germinal retinoblastoma and Down syndrome was treated with diode
      laser and systemic carboplatin and low-dose vincristine, with gradual dose
      escalation. Etoposide and cyclosporine were later added for a greater tumor
      response. After cyclosporine was added, the patient was hospitalized due to
      vincristine toxicity. The vincristine dose was further lowered, and periocular
      carboplatin injections were given to establish control of intraocular disease.
      RESULTS: The tumors regressed after 11 sessions of laser and chemotherapy.
      Because of residual vitreous seeding in the right eye, a series of two periocular
      carboplatin injections were given. Six more laser sessions were applied to the
      tumors. There is no evidence of active retinoblastoma after 11 months of follow
      up. CONCLUSION: Because of increased chemosensitivity in patients with Down
      syndrome, it is important to reduce systemic drug dosages and consider augmenting
      local therapy in retinoblastoma cases.

PMID- 25390124
TI  - Uterine papillary serous carcinoma metastatic to the choroid.
AB  - PURPOSE: To report an unusual case of choroidal metastasis from uterine papillary
      serous carcinoma presenting as a choroidal hemorrhage. METHODS: A 70-year-old
      woman with a history of Stage IV endometrial cancer presented with sudden loss of
      vision and pain behind the right eye. Clinical examination revealed a choroidal
      hemorrhage with retinal detachment. The clinical findings, results of imaging
      studies, and pathologic findings are described. RESULTS: The patient underwent
      drainage of the choroidal hemorrhage but developed a painful, blind eye resulting
      from secondary glaucoma that was refractory to maximal medical therapy.
      Examination of the drained choroidal fluid showed no malignant cells. The patient
      elected for enucleation of the affected eye, and histopathologic analysis was
      consistent with uterine papillary serous carcinoma metastatic to the choroid. The
      patient tolerated the procedure well. However, she entered hospice shortly after
      surgery to receive palliative care for her metastatic disease. CONCLUSION: Rare
      cases of uterine cancer metastasizing to the uvea have been reported. To our
      knowledge, this is the first case of uterine papillary serous carcinoma with
      uveal metastasis. Metastatic disease involving the uvea should be considered in
      the differential diagnosis for a patient presenting with pain and sudden loss of
      vision, particularly when the patient has a known primary malignancy.
      Histopathology and cytology can assist in identifying a uveal mass as metastatic.

PMID- 25390125
TI  - Unusual presentation of metastatic carcinoma to the eye.
AB  - PURPOSE: To describe four patients with an unusual presentation of metastatic
      carcinoma to the eye, diagnosed by histopathologic and immunohistochemical
      evaluation of vitrectomy material. METHODS: Retrospective case series of four
      patients with metastatic carcinoma to the retina/vitreous. The New York Eye and
      Ear Infirmary database was searched to identify patients with metastatic
      carcinoma to the retina or vitreous, diagnosed from 1995 to 2006. Diagnoses were
      established through histopathologic and immunohistochemical evaluation of
      vitreous fluid obtained via pars plana vitrectomy. RESULTS: The New York Eye and
      Ear Infirmary Pathology database search resulted in 19,149 vitrectomy specimens,
      4 of which were positive for metastatic carcinoma. The diagnosis was clinically
      unsuspected in three patients. The oncologic work-up revealed the origin of
      metastases to be from the breast in two patients and from the lung in two
      patients. CONCLUSION: Metastatic carcinoma to the eye can present with clinically
      innocuous metastases, masquerading as epiretinal membrane and macular hole,
      central serous chorioretinopathy, rhegmatogenous retinal detachment, retinal
      granuloma, and endophthalmitis. These findings suggest that submission of
      vitrectomy specimens for pathologic evaluation should be considered in patients
      with an oncologic history or in those with atypical clinical presentation.

PMID- 25390126
TI  - Spontaneously resolved macroaneurysm associated with a congenital anomalous
      retinal artery.
AB  - PURPOSE: To report the outcome of retinal artery macroaneurysm associated with a
      congenital anomalous retinal artery. METHODS: The patient was examined with
      ophthalmoscopy and fluorescein angiography. RESULTS: A 60-year-old woman
      presented with visual acuity of 20/80 in her right eye. She was found to have an
      abnormal retinal vessel emerging from the optic disk, passing toward the center
      of the macula, and looping back toward the disk. The center of the loop had a
      leaking macroaneurysm, which was treated conservatively. At the 4-month follow-up
      visit, the visual acuity in the right eye had improved to 20/20 with resolution
      of most of the macular edema, exudates, and hemorrhage. CONCLUSION: This case
      demonstrates that retinal artery macroaneurysm can be successfully managed with a
      conservative approach, even when associated with a congenital anomalous retinal
      vessel.

PMID- 25390127
TI  - Rosiglitazone toxicity: accidental overdose leading to macular edema.
AB  - BACKGROUND/PURPOSE: To highlight the clinical effects of rosiglitazone overdose.
      METHODS: Case report, observational. RESULTS: A 60-year-old Chinese man
      accidentally ingested 20 mg rosiglitazone. His usual dose was 2 mg once in the
      morning. Complications of drug overdose were monitored. He consequently developed
      right mild macular edema. This resolved spontaneously without laser treatment. No
      systemic toxicity, hypoglycemia, or peripheral edema was observed. CONCLUSION:
      Rosiglitazone overdose causes acute macular edema that resolves spontaneously.

PMID- 25390128
TI  - Management of macular hole with choroidal coloboma.
AB  - PURPOSE: Choroidal colobomas represent failure of closure of the fetal fissure
      during embryogenesis. Eyes with colobomas can develop complex retinal
      detachments. We present a case of a patient presenting with a macular hole in her
      only useful eye with an extramacular choroidal coloboma. METHODS: A 56-year-old
      woman was referred with a 3-month history of central distortion and blurring of
      vision in her right eye. The left eye was amblyopic with microphthalmos. She was
      found to have a Stage 2 macular hole in her right eye with a large inferonasal
      coloboma extending underneath the inferior arcade. The patient underwent
      vitrectomy with induction of a posterior vitreous detachment, internal limiting
      membrane peeling, and insertion of C2F6 gas. RESULTS: During the vitrectomy,
      there was some difficulty in inducing a posterior vitreous detachment along the
      edges of the coloboma, but otherwise, the stronger vitreous adhesion did not
      interfere with the procedure. The patient responded well to surgery, and the
      macular hole closed. CONCLUSION: The occurrence of a macular hole in an eye with
      choroidal coloboma has not been previously described. The presence of a coloboma
      causes uncertainty about performing a vitrectomy, because colobomatous eyes are
      at risk of retinal detachment. This case demonstrates that vitrectomy and
      induction of a posterior vitreous detachment does not necessarily lead to retinal
      detachments in such cases, and successful management of a condition like macular
      holes is possible in the presence of retinal coloboma.

PMID- 25390129
TI  - Retinal vascular occlusion during in vitro fertilization.
AB  - PURPOSE: To describe a case of human retinal vascular occlusion during in vitro
      fertilization. METHODS: A single case report of a 30-year-old woman who developed
      decreased central vision in her left eye with inferonasal scotoma while on a
      gonadotropin-releasing hormone agonist treatment protocol. RESULTS: The patient's
      laboratory tests and biochemical profile were normal. Fundoscopy revealed
      moderate tortuosity of both temporal vascular arcades and dilation of the
      inferior temporal vein with a blotchy hemorrhage. The superotemporal macular area
      was swollen and pale. Fluorescein angiography demonstrated an incomplete central
      retinal vein occlusion accompanied by branch retinal arterial occlusion in the
      left eye. Six months later, her vision improved to 20/32, and the retina
      recovered normal color. CONCLUSION: Retinal vascular occlusion can occur during a
      controlled ovarian hyperstimulation with gonadotropin-releasing hormone agonists.

PMID- 25390130
TI  - A novel missense mutation in the rds/peripherin gene associated with retinal
      pattern dystrophy.
AB  - PURPOSE: To present a case of retinal pattern dystrophy and the genetic analysis
      identifying the molecular basis of the disease. METHODS: A 46-year-old man with a
      6-year history of vision loss of the right eye. A clinical exam revealed pattern
      dystrophy of the retina bilaterally, with more involvement of the right eye.
      RESULTS: Molecular diagnostic analysis of the retinal degeneration slow
      (RDS)/peripherin gene showed a novel change at nucleotide position 665 (G665C)
      that alters the amino acid at position 222 from cysteine to serine (C222S).
      CONCLUSION: This study describes an RDS/peripherin mutation in a case of retinal
      pattern dystrophy, which is the first identification of this mutation to our
      knowledge.

PMID- 25390131
TI  - Obliterative idiopathic juxtafoveolar telangiectasis: a 25-year follow-up.
AB  - PURPOSE: To report findings over 25 years of follow-up on a case of bilateral
      obliterative idiopathic juxtafoveolar retinal telangiectasis. METHOD: Case
      report. RESULTS: A 25-year-old white man with obliterative idiopathic
      juxtafoveolar retinal telangiectasis presented with a visual acuity of 20/30 in
      the right eye and 20/40 in the left. Fluorescein angiography revealed bilateral
      enlarged foveal avascular zones and late perifoveal leakage. Six years after
      presentation, the foveal avascular zone had enlarged only slightly in both eyes
      and the leakage had almost entirely subsided. For the next 19 years, the visual
      acuity and clinical findings have remained unchanged. His most recent visual
      acuity was 20/25 in the right eye and 20/40 in the left. No treatment was given
      throughout the entire follow-up period of 25 years. CONCLUSION: Obliterative
      idiopathic juxtafoveolar retinal telangiectasis is a rare disorder that may
      initially progress with subsequent stabilization and good long-term visual
      outcome.

PMID- 25390132
TI  - Scleral buckle removal as treatment for persistent subfoveal fluid after scleral
      buckle surgery for retinal detachment.
AB  - PURPOSE: To describe the removal of scleral buckle (SB) as a potential treatment
      option for persistent subfoveal fluid after SB retinal reattachment surgery.
      METHODS: Case report of a single patient. RESULTS: A 56-year-old man with a
      preoperative best-corrected visual acuity of 20/20 underwent SB surgery for a
      macula-on retinal detachment. Postoperatively he developed subfoveal fluid with
      best-corrected visual acuity ranging from 20/30 to 20/40. Nine months after the
      original retinal reattachment surgery, the patient underwent SB removal as a
      treatment for persistent subfoveal fluid and incomplete recovery of visual
      acuity. One week after SB removal, the subfoveal fluid was substantially
      diminished and best-corrected visual acuity had returned to 20/20. CONCLUSION:
      This case suggests that removal of SB after retinal reattachment may be a viable
      treatment option in patients with persistent subfoveal fluid on optical coherence
      tomography and incomplete recovery of preoperative visual acuity.

PMID- 25390133
TI  - 2009 scientific reviewers.

PMID- 25390134
TI  - Sickle-cell disease.

PMID- 25390135
TI  - Perspective: we need a global solution.

PMID- 25390136
TI  - Gene therapy: editorial control.

PMID- 25390137
TI  - Stem cells: creating a cure-all.

PMID- 25390138
TI  - Perspective: thinking beyond survival.

PMID- 25390139
TI  - Epidemiology: a moving target.

PMID- 25390140
TI  - Drug development: a complicated path.

PMID- 25390141
TI  - Index 2014 Global.

PMID- 25390142
TI  - Introducing the Index.

PMID- 25390143
TI  - Global overview.

PMID- 25390144
TI  - Q&A: healthy progress.

PMID- 25390145
TI  - North America.

PMID- 25390146
TI  - North & western Europe.

PMID- 25390147
TI  - East & Southeast Asia.

PMID- 25390148
TI  - Neurobiology: life beyond the pain.

PMID- 25390149
TI  - Central, East & South Europe.

PMID- 25390150
TI  - Australasia & Pacific Islands.

PMID- 25390151
TI  - West Asia.

PMID- 25390152
TI  - Central & South Asia.

PMID- 25390153
TI  - Middle & South America.

PMID- 25390154
TI  - Africa.

PMID- 25390155
TI  - A guide to the Nature Index.

PMID- 25390156
TI  - Nature Index tables.

PMID- 25390157
TI  - Involvement of the Antioxidant Effect and Anti-inflammatory Response in Butyrate
      Inhibited Vascular Smooth Muscle Cell Proliferation.
AB  - Epigenetic mechanisms by altering the expression and, in turn, functions of
      target genes have potential to modify cellular processes that are characteristics
      of atherosclerosis, including inflammation, proliferation, migration and
      apoptosis/cell death. Butyrate, a natural epigenetic modifier and a histone
      deacetylase inhibitor (HDACi), is an inhibitor of vascular smooth muscle cell
      (VSMC) proliferation, a critical event in atherogenesis. Here, we examined
      whether glutathione peroxidases (GPxs), a family of antioxidant enzymes, are
      modulated by butyrate, contributing to its antiproliferation action on VSMC
      through the regulation of the inflammatory response by using western blotting,
      immunostaining methods and activity assay. Treatment of VSMC with butyrate not
      only upregulates glutathione peroxidase (GPx) 3 and GPx4, but also increases the
      overall catalytic activity of GPx supporting involvement of antioxidant effect in
      butyrate arrested VSMC proliferation. Moreover, analysis of the redox-sensitive
      NF-kappaB transcription factor system, the target of GPx, reveals that butyrate
      causes downregulation of IKKalpha, IKKbeta, IkBalpha and NF-kappaBp65 expression
      and prevents NF-kappaBp65 phosphorylation at serine536 causing inhibition of the
      expression NF-kappaB target inflammatory genes, including inducible nitric oxide
      synthase, VCAM-1 and cyclooxygenase-2. Overall, these observations suggest a link
      between the antioxidant effect and anti-inflammatory response in butyrate
      arrested VSMC proliferation, accentuating the atheroprotective and therapeutic
      potential of natural products, like butyrate, in vascular proliferative diseases.

PMID- 25390159
TI  - The role and preparation of case reports: resident education.

PMID- 25390158
TI  - Genotyping data and novel haplotype diversity of STR markers in the SLC26A4 gene
      region in five ethnic groups of the Iranian population.
AB  - BACKGROUND AND AIMS: SLC26A4 gene mutations are the second currently identifiable
      genetic cause of autosomal recessive nonsyndromic hearing loss after GJB2
      mutations. Because of the extensive size of the SLC26A4 gene and the variety of
      mutations, indirect diagnosis using linkage analysis has been suggested.
      Therefore, in this investigation three potential short tandem repeat (STR)
      markers related to this region including D7S2420, D7S496, and D7S2459 were
      selected for further analysis. METHODS: The characteristics and haplotype
      frequency of the markers were examined for the first time in five ethnic groups
      of the Iranian population including Fars, Azari, Turkmen, Gilaki, and Arab using
      the polymerase chain reaction followed by fluorescent capillary electrophoresis.
      RESULTS were analyzed by GeneMarker HID Human STR Identity, GenePop,
      Microsatellite tools, PowerMarker 3.25, and Arlequin 3.5 software. RESULTS:
      Analysis of the allelic frequency revealed the presence of 11, 10, and 8 alleles
      for D7S2420, D7S496, and D7S2459 markers, respectively, in the Iranian
      population. The detailed analysis of each ethnic group was reported. Calculated
      polymorphism information content values were above 0.7 in the Iranian population.
      Pairwise linkage disequilibrium (LD) revealed a significant LD in pairing markers
      of D7S2420-D7S496 and in D7S496-D7S2459. Estimation of the haplotype frequency
      showed the presence of 20, 13, 15, 15, and 20 informative haplotypes in Fars,
      Azari, Turkmen, Gilaki, and Arabian ethnics, respectively. CONCLUSION: Together,
      the investigated markers could be suggested as powerful tools for linkage
      analysis of SLC26A4 gene mutations in the Iranian population.

PMID- 25390160
TI  - Centrifugal enlargement of macular hole and macular detachment in a patient with
      bilateral giant macular holes.
AB  - PURPOSE: To report the detailed vitreomacular morphology of a case of progressive
      enlargement and macular detachment secondary to and several years after the
      development of bilateral giant macular holes using optical coherence tomography.
      METHODS: Using optical coherence tomography, both eyes of a patient with
      bilateral giant macular holes were examined. RESULTS: A 33-year-old woman had
      bilateral giant macular holes at the first visit. At the 5-year follow-up visit,
      the macular hole had enlarged centrifugally in the right eye, and a macular
      detachment developed beyond the arcade vessels in the left eye. Optical coherence
      tomography showed retinoschisis in the right eye around the edges of the hole and
      a macular detachment in the left eye with vitreoretinal adhesion temporal to both
      holes. CONCLUSION: These optical coherence tomography findings suggested that
      vitreomacular traction at the temporal edge of the hole may have resulted in
      progressive centrifugal enlargement of the hole in both eyes and then the macular
      detachment occurred in the left eye.

PMID- 25390161
TI  - Surgical treatment of an enlarging retinal cyst associated with a choroidal
      coloboma.
AB  - PURPOSE: The purpose of this study was to describe a case of an enlarging retinal
      cyst associated with a choroidal coloboma, which was treated surgically in a
      child. METHODS: A retrospective case report. RESULTS: A funduscopic examination
      of a 5-year-old boy revealed a retinal cyst in the inferonasal area of the right
      fundus. The corrected visual acuity at initial examination was 20/40. During the
      follow-up period, the retinal cyst waxed and waned spontaneously. Seven years
      after the first examination, the visual acuity decreased to 20/1000 due to an
      enlarged retinal cyst, which obscured the macula and did not recover. At the 9
      year follow-up, barrier laser around the retinal cyst and pars plana vitrectomy
      with retinectomy, internal drainage of the cyst, and 14% C3F8 gas tamponade were
      performed. There was a colobomatous choroidal defect at the base of the retinal
      cyst. The patient's visual acuity improved to 20/25, and the retina remained flat
      at the 2-year follow-up postoperatively. CONCLUSION: We managed a very rare case
      of a retinal cyst associated with a choroidal coloboma. During the 9-year follow
      up, the retinal cyst waxed and waned spontaneously. The enlarging retinal cyst
      that caused visual impairment was treated successfully by barrier laser and
      vitreous surgery. The visual acuity recovered completely.

PMID- 25390162
TI  - Extraocular seeding of choroidal melanoma after a transretinal biopsy with a 25
      gauge vitrector.
AB  - PURPOSE: To report an isolated case of extraocular seeding of choroidal melanoma
      after a transretinal biopsy. METHODS: A 74-year-old man with a choroidal melanoma
      in the left eye underwent a 3-port transconjunctival 25-gauge transretinal biopsy
      (for cytogenetic prognostication) followed by proton beam radiotherapy. Biopsy
      showed the melanoma to be predominantly of spindle cell type with chromosome 3
      loss. He presented 14 months later with two pigmented conjunctival lesions,
      corresponding to the site of the pars plana sclerotomy. RESULTS: Excision biopsy
      of the conjunctival lesions confirmed subconjunctival seeding of melanoma cells
      at the sites of sclerotomy. CONCLUSION: The seeding of melanoma corresponded to
      the sites of sclerotomy, indicating extraocular seeding of the primary tumor
      after transretinal biopsy. We discuss the possible reasons for this occurrence
      and strategies to prevent extraocular seeding of melanoma after transretinal
      biopsy.

PMID- 25390163
TI  - Cutaneous melanoma metastatic to the vitreous cavity.
AB  - PURPOSE: To report a case of cutaneous melanoma metastatic to the vitreous
      cavity. METHODS: Retrospective case report. A 72-year-old white man with a
      history of cutaneous melanoma but no known distant metastases presented with
      floaters and decreased vision. RESULTS: The patient was initially treated for a
      presumptive diagnosis of ocular toxoplasmosis. After failure to respond to
      treatment, he underwent diagnostic pars plana vitrectomy. Pathology of the
      vitreous specimen was suggestive of metastatic melanoma, and systemic workup
      revealed metastases to the brain. CONCLUSION: In patients with a known history of
      cutaneous melanoma presenting with ocular inflammation, a high index of suspicion
      for metastatic disease should be maintained.

PMID- 25390164
TI  - Bilateral angle-closure glaucoma and multifocal choroiditis as a first
      presentation in hodgkin lymphoma.
AB  - PURPOSE: To report atypical ocular manifestations in two patients with
      undiagnosed Hodgkin lymphoma. METHODS: Observational case report. RESULTS: The
      first patient, a 27-year-old man, presented with bilateral acute angle-closure
      glaucoma secondary to uveal effusion. Histopathology of chest lymph nodes
      obtained by mediastinoscopy revealed nodular sclerosing Hodgkin lymphoma. Ocular
      signs resolved after systemic chemotherapy. The second patient, a 56-year-old
      man, presented with bilateral multifocal choroiditis. Extensive biologic and
      microbiologic examinations were negative. Pathologic lymph nodes were detected in
      the anterior mediastinum. The histopathologic examination of the nodes after
      mediastinoscopy revealed nodular sclerosing Hodgkin lymphoma. Systemic
      chemotherapy was instituted. The patient encountered a major increase in the
      multifocal choroiditis within 3 days after the second chemotherapy injection.
      High-dose intravenous corticosteroid therapy was initiated. No recurrence of
      choroidal lesions was observed after the treatment completion. CONCLUSION: These
      two patients presented with bilateral paraneoplastic uveal tract involvement as
      initial presentation of Hodgkin lymphoma. Systemic corticosteroid therapy may be
      associated with systemic chemotherapy to obtain complete remission of the ocular
      inflammatory activity.

PMID- 25390165
TI  - Retinal neovascularization after internal carotid artery occlusion.
AB  - PURPOSE: To report a case of retinal neovascularization after surgical ligation
      of the internal carotid artery for treatment of direct carotid-cavernous fistula.
      METHODS: Case report. RESULT: A 44-year-old Asian woman presented with unilateral
      retinal neovascularization and vitreous hemorrhage. Surgical ligation of the
      ipsilateral internal carotid artery had been performed 14 years earlier as a
      treatment for carotid-cavernous fistula after failed attempts at fistula
      embolization. Vitrectomy was performed for removal of nonclearing vitreous
      hemorrhage, with intraoperative peripheral retinal ablation and cryotherapy of
      the lesion. CONCLUSION: We report a case of retinal neovascularization associated
      with total occlusion of the ipsilateral internal carotid artery 14 years earlier.

PMID- 25390166
TI  - West nile virus occlusive retinal vasculitis.
AB  - PURPOSE: To report a case of West Nile virus meningoencephalitis presenting with
      simultaneous chorioretinitis in the right eye and occlusive retinal vasculitis in
      the left eye. METHODS: Case report. Main outcome measures included ocular
      examination, intravenous fluorescence angiography, indocyanine green, color
      fundus photography, and serologic testing for West Nile virus. RESULTS: A 45-year
      old white woman presented with severe loss of vision in the left eye (count
      fingers at 3 feet) 2 weeks after an episode of hospitalization for fever of
      unknown origin. Examination showed extensive retinal opacification and edema in
      the left eye with arteriolar narrowing. Intravenous fluorescence angiography
      confirmed delayed venous return superiorly, multiple arteriolar occlusions, large
      area of nonperfusion, and vascular staining and leakage. Indocyanine green
      highlighted bilateral well-deliniated hypocyanescent choroidal lesions
      corresponding to the subretinal lesions seen by ophthalmoscopy. Indocyanine green
      allowed identification of additional lesions that were not initially detected on
      intravenous fluorescence angiography and ophthalmoscopy. CONCLUSION: Occlusive
      retinal vasculitis is a rare yet important ocular manifestation of West Nile
      virus infection. It may occur in young patients without diabetes, and unlike West
      Nile virus chorioretinitis, it is often associated with poor visual outcome.

PMID- 25390167
TI  - Dengue Fever presenting with macular hemorrhages.
AB  - PURPOSE: To report ocular manifestations in cases of previously undiagnosed
      dengue fever. METHODS: A retrospective study was done to evaluate the cause of
      sudden painless loss of vision in three cases with history of fever. Detailed
      systemic evaluation and ophthalmologic examination consisting of fundus
      photographs, fundus fluorescein angiography, and optical coherence tomography
      were done, where needed. RESULTS: All three patients tested positive for dengue
      serology, which had been undiagnosed earlier. Retinal hemorrhages were found in
      all three patients, while one patient also showed evidence of retinitis-like
      lesions. He was treated with oral steroids and showed improvement in visual
      acuity over a period of 6 weeks. Two of the three patients had subhyaloid
      hemorrhages, which were seen to resolve spontaneously. CONCLUSION: A significant
      subset of patients with mild form of dengue fever may go undiagnosed.

PMID- 25390168
TI  - Rickettsial retinitis: acute unilateral vision loss with cystoid macular edema
      and stellate maculopathy.
AB  - PURPOSE: To report on the presentation and treatment of a patient with infectious
      posterior segment uveitis because of infection with Rickettsia rickettsii.
      METHODS: Interventional case report. We conducted a retrospective chart review of
      a 39-year-old man who presented with a history of acute vision loss in his right
      eye over a 6-day period. Vision at presentation in the involved eye was 2/200,
      with mild conjunctival injection, trace anterior chamber cell, moderate vitritis,
      localized retinitis and retinal hemorrhages, and severe macular edema. The left
      eye had 20/20 vision and was normal on examination. History was notable for a
      tick bite followed by high fevers, 1 month before presentation, at which time his
      family physician diagnosed mononucleosis syndrome with low platelets. RESULTS: A
      serum Rickettsia rickettsii test was positive. He was treated with oral
      doxycycline followed by corticosteroids. Vision gradually improved to 20/20 with
      minimal residual metamorphopsia. CONCLUSION: Only ten cases of Rocky Mountain
      spotted fever-related uveitis have been reported. The current case is unique
      because of the delayed onset of ophthalmic complications after the tick bite, its
      unilateral nature, dramatic improvement in acuity after treatment, and lack of
      associated rash.

PMID- 25390169
TI  - A case of retinal injury by a violet light-emitting diode.
AB  - PURPOSE: To describe the first case of retinal injury by a misuse of a toy using
      light-emitting diode. METHODS: A 15-year-old male Japanese student received
      irradiation on his right eye by a 5 mW light-emitting diode of 410 nm wavelength
      for 20 seconds in 2 days. He noticed decreased vision and central scotoma
      approximately 2 weeks later from these events. The mechanism of injury was
      evaluated from the estimated irradiance on the retina by comparison with
      experimental threshold data published. RESULTS: Chorioretinal atrophy with visual
      loss and central scotoma has remained on the fovea. The patient received an
      estimated dose of 1.58 J/cm 2 times, which was close to the experimentally
      determined radiant exposure for photochemical injury of rat retina. CONCLUSION:
      The violet light from light-emitting diodes is a potential hazard for the retina,
      and thus, direct viewing into the beam should be avoided. Children, especially,
      should not be allowed to play with such toys without being carefully instructed
      about their proper use and fully supervised.

PMID- 25390170
TI  - Diffuse macular edema in niacin-induced maculopathy may resolve with dosage
      decrease.
AB  - PURPOSE: To report on a patient with niacin-induced cystic maculopathy that
      resolved with dosage decrease, not discontinuation, of niacin therapy for
      dyslipidemia. METHODS: Retrospective case report. The patient was being followed
      for vision changes, but his niacin therapy was managed elsewhere. RESULTS:
      Results of the decrease in niacin dosage show clear evidence (with optical
      coherence tomography) of resolution of retinal edema. CONCLUSION: Our conclusion
      is that niacin's toxicity has a threshold, and dosage decrease below this
      threshold allows continuation of therapy at the lower dosage without clinically
      evident adverse effects on the retina.

PMID- 25390171
TI  - Intravitreal bevacizumab and ranibizumab for choroidal neovascularization
      secondary to endogenous endophthalmitis.
AB  - PURPOSE: To report two patients with endogenous endophthalmitis complicated by
      choroidal neovascularization managed with intravitreal bevacizumab (Avastin,
      Genentech, Inc., South San Francisco, CA) or ranibizumab (Lucentis, Genentech,
      Inc., South San Francisco, CA) and their respective outcomes. METHODS:
      Retrospective chart review of 2 patients, one a 54-year-old diabetic woman on
      chemotherapy for pemphigus vulgaris and the other a 77-year-old diabetic male
      with cellulitis, who were treated for endogenous endophthalmitis complicated by
      choroidal neovascularization. RESULTS: The patients were managed with off-label
      intravitreal anti-vascular endothelial growth factor injections. The first
      patient received one dose of intravitreal bevacizumab (Avastin) with improvement
      in vision and anatomy. The second patient received four doses of intravitreal
      ranibizumab (Lucentis) with improvement in vision and structural appearance.
      CONCLUSION: Choroidal neovascularization secondary to endogenous endophthalmitis
      responds to anti-vascular endothelial growth factor therapy with bevacizumab or
      ranibizumab.

PMID- 25390172
TI  - Intravitreal bevacizumab (avastin) for choroidal neovascularization associated
      with deferoxamine retinopathy.
AB  - PURPOSE: To report the effect of antivascular endothelial growth factor therapy
      for choroidal neovascularisation associated with deferoxamine toxicity. METHOD:
      In an interventional case report, intravitreal antivascular endothelial growth
      factor therapy was used for the treatment of a choroidal neovascularization in a
      patient with deferoxamine retinopathy. RESULTS: A 54-year-old woman with beta
      thalassemia intermedia and known deferoxamine toxicity presented with recent
      vision loss to the left eye secondary to a choroidal neovascular membrane. Visual
      acuity had decreased from 20/30 to 20/80 in the left eye. Funduscopic examination
      and fluorescein angiography revealed diffuse retinal pigment epithelial mottling
      and a choroidal neovascular membrane. Treatment with three doses of intravitreal
      bevacizumab led to a good structural outcome and improvement of the visual
      acuity. The patient later developed a choroidal neovascular membrane in the right
      eye. Similar treatment with intravitreal bevacizumab also led to a rapid
      structural resolution of the lesion, albeit with a more modest improvement in the
      visual acuity. CONCLUSION: Therapy with intravitreal bevacizumab might be an
      option for the treatment of choroidal neovascularization in the context of
      deferoxamine toxicity.

PMID- 25390173
TI  - ELECTRICAL INJURY INDUCED BILATERAL PERIPAPILLARY MERIDIONAL RETINA-CHOROIDAL
      ATROPHY: A Case Report.
AB  - PURPOSE: To illustrate the clinical findings in a patient who experienced an
      electrical shock injury. METHODS: Observational case report. A 54-year-old man
      who experienced an electrical shock injury was followed up with fundus
      photography, fluorescein angiography, and indocyanine green angiography. Visual
      acuity, electroretinography, and visual field were also performed. The visual
      acuity of the right eye was 20/25 and the left eye was 20/20. Bilateral
      meridional atrophy areas were found around the optic nerve in fundus color
      images. Axial symmetrical meridional atrophies around the optic disk in both eyes
      were found in the patient's fundus fluorescein angiography and indocyanine green
      angiography images. RESULTS: Atrophy of bilateral retina and choroid can be found
      on fundus autofluorescence, fundus fluorescein angiography, and indocyanine green
      angiography in this electrical current-injured case, which looks like meridional
      direction from superior temporal to inferior nasal through optic disk.
      CONCLUSION: We report a rare case of bilateral peripapillary meridional retina
      choroidal atrophy after electrical injury. Because of the variable timing and
      spectrum of ocular findings, patients experiencing electrical injury without
      profound vision loss should undergo long observation.

PMID- 25390174
TI  - Intraretinal deposition of triamcinolone acetonide after treatment of diabetic
      macular edema.
AB  - PURPOSE: To report a case of intraretinal triamcinolone acetonide crystal
      deposition visualized both clinically and on optical coherence tomography after
      intravitreal injection for diabetic macular edema refractory to focal/grid laser
      treatment. METHODS: Observational case report. A 46-year-old man with severe
      bilateral diabetic macular edema underwent focal/grid laser therapy, Avastin
      (Genetech, Inc., South San Francisco, CA) injections, and multiple intravitreal
      triamcinolone acetonide treatments but remained refractory to treatment. RESULTS:
      Visual acuity continued to worsen, and clinical and optical coherence tomography
      examination revealed scattered hyperreflective deposits throughout the retina.
      CONCLUSION: Intravitreal triamcinolone acetonide can deposit within the retina
      after treatment of refractory diabetic macular edema.

PMID- 25390175
TI  - Retinal vascular anomaly in sturge-weber syndrome.
AB  - PURPOSE: We report a unique case of a 7-year-old girl who presented with an
      unusual combination of findings, including facial hemangioma, choroidal
      hemangioma, and retinal vascular anomaly. METHODS: Case report and literature
      review. RESULTS: Examination revealed a hemangioma on the right midface. The
      acuity was 20/200 in the affected eye. Enlarged episcleral vessels were present.
      There was a large choroidal hemangioma measuring 4.8 mm in thickness underlying
      the macula and large dilated white retinal vessels extending to a partially
      involuted tumor in the periphery. Fluorescein angiography confirmed perfusion of
      the abnormal retinal vessels, and magnetic resonance imaging showed enhancement
      consistent with choroidal hemangioma with no other intracranial abnormalities. No
      other abnormalities were noted on physical examination. CONCLUSION:
      Neurocutaneous syndromes including Sturge-Weber, Parkes Weber, and Klippel
      Trenaunay may show significant degrees of overlapping findings. This case is
      unique in that this patient presented with both choroidal and retinal tumors as
      part of Sturge-Weber syndrome with a facial hemangioma.

PMID- 25390176
TI  - Case report: ampiginous chorioretinopathy associated with eales disease in a
      patient with presumed tuberculosis.
AB  - PURPOSE: The purpose of this study was to present a case of ampiginous
      chorioretinopathy followed by Eales disease in association with mycobacterium
      tuberculosis infection. METHODS: Case report. RESULTS: The patient presented with
      signs of ampiginous chorioretinopathy, which subsequently developed into Eales
      disease with a background of mycobacterium tuberculosis infection. CONCLUSION:
      This case describes the unusual manifestations of tuberculosis in the retina.

PMID- 25390177
TI  - Choroidal biopsy of a patient with AIDS and systemic tuberculosis: a
      clinicopathologic case report.
AB  - PURPOSE: To report a case of Mycobacterium tuberculosis choroidal granuloma
      confirmed by the presence of acid-fast bacilli seen on subretinal biopsy of the
      choroidal lesion. METHODS: Observational case report. A 54-year-old woman with
      AIDS and systemic tuberculosis reported decreased vision in the right eye for 2
      months duration. RESULTS: Subretinal biopsy showed granulomatous inflammation,
      and acid-fast bacilli were identified on the acid-fast bacilli stain. CONCLUSION:
      In cases of presumed tuberculosis choroidal granuloma not initially responsive to
      tuberculosis therapy, biopsy of the choroidal mass can be beneficial to confirm
      the diagnosis and guide treatment.

PMID- 25390178
TI  - Case report: retinopathy in a patient with cold hemagglutinin disease.
AB  - PURPOSE: We describe abnormalities of retinal vasculature and blood flow in a
      patient with cold hemagglutinin disease. METHOD: Case report and literature
      review using the PubMed database. RESULTS: A man with cold hemagglutinin disease
      and no visual symptoms was referred to the Eye Department with retinal
      abnormalities found during a routine optometrist examination. He was found to
      have scattered retinal hemorrhages, abnormal retinal vasculature resembling
      neovascularization (but that did not show leakage on fundus fluorescein
      angiography), and aggregated material flowing visibly in the retinal vessels.
      CONCLUSION: No specific descriptions of retinopathy related to cold hemagglutinin
      disease have been previously published. We suggest that the abnormalities are
      secondary to areas of retinal ischemia, resulting in the development of a form of
      collateral circulation.

PMID- 25390179
TI  - Scleral fixation intraocular lens as a barrier for silicone oil in traumatic
      aphakia, aniridia, and recurrent retinal detachment:case report.
AB  - PURPOSE: We report a patient with recurrent retinal detachment complicated with
      traumatic aniridia and aphakia, which was successfully managed by scleral
      fixation polymethyl methacrylate posterior chamber intraocular lens (PMMA PCIOL)
      and vitrectomy with silicon oil tamponade. METHOD: Interventional case report.
      RESULTS: A 35-year-old man with traumatic aniridia, aphakia, and recurrent
      retinal detachment who received the combined surgery of scleral fixation PMMA
      PCIOL and vitrectomy with silicon oil tamponade. The patient had favorable visual
      outcome. The retina was reattached and the cornea remained clear without silicon
      oil in the anterior chamber after 1 year. CONCLUSION: The scleral fixation PMMA
      PCIOL can retain the silicone oil in the vitreous cavity for reattaching the
      retina and can also protect the corneal endothelium from contact with the
      silicone oil in the case of aniridia, aphakia, and retinal detachment.

PMID- 25390180
TI  - Simultaneous presentation of branch retinal artery occlusion and vitreomacular
      traction.
AB  - PURPOSE: To report a case of simultaneous presentation of branch retinal artery
      occlusion and vitreomacular traction and the auxiliary role of optical coherence
      tomography and fluorescein angiogram in the management of this case. METHODS: A
      42-year-old female patient presented with diminution of vision in the left eye.
      Visual acuity was 20/200. Ocular examination revealed the presence of whitening
      of the retina along the superotemporal arcade, suggestive of branch retinal
      artery occlusion. Fluorescein angiogram showed delayed filling of the
      superotemporal artery consistent with branch retinal artery occlusion along with
      uncharacterisitic leakage at the fovea. Optical coherence tomographic scan
      through the fovea revealed vitreomacular traction with distortion of foveal
      contour. The patient was diagnosed as a case of branch retinal artery occlusion
      with vitreomacular traction. The patient underwent vitrectomy for the hyaloidal
      traction on the macula. RESULTS: Postoperatively, the visual acuity in the left
      eye improved to 20/20 with resolution of dye leakage on fluorescein angiogram
      with normal foveal contour on optical coherence tomography. CONCLUSION: Branch
      retinal artery occlusion and vitreomacular traction can present simultaneously,
      and fluorescein angiogram with optical coherence tomography has a complementary
      role in the management of such cases.

PMID- 25390181
TI  - FUNDUS FINDINGS IN A PATIENT WITH alpha-METHLYACYL-COA RACEMASE DEFICIENCY.
AB  - PURPOSE: To describe the ocular findings in a patient with alpha-methylacyl-CoA
      racemase deficiency. METHODS: Case report. RESULTS: A 45-year-old white man
      presented with seizures, hemiparesis, and altered mental status. As a part of an
      extensive investigation, an ophthalmic evaluation was performed. Funduscopic
      examination of both eyes showed a bull's-eye pattern pigmentary maculopathy.
      Fluorescein angiography demonstrated a prominent choroidal circulation without
      dye leakage. Optical coherence tomography showed a significant thinning of the
      macula with moderate nerve fiber layer loss. Serum pristanic levels were
      significantly elevated, and alpha-methylacyl-CoA racemase deficiency was
      confirmed by urine and bile analysis. The patient's clinical condition improved
      after plasma exchange and dietary restriction of fatty acids. CONCLUSION: alpha
      Methylacyl-CoA racemase deficiency is a rare peroxisomal enzyme disorder
      previously described in only six patients, two of whom had pigmentary
      retinopathies. This article describes the third patient with retinopathy and the
      first with published fundus findings.

PMID- 25390182
TI  - Resolution of serous maculopathy associated with optic disk pits and
      incontinentia pigmenti using oral acetazolamide.
AB  - BACKGROUND: Optic disk pits are a congenital optic disk anomaly frequently
      associated with serous macular detachment. METHODS: A case of optic disk pits
      associated with serous maculopathy in a patient with incontinentia pigmenti is
      presented. The patient was treated with oral acetazolamide. RESULTS: Over the
      course of 1 year, treatment with oral acetazolamide resulted in the complete
      resolution of subretinal fluid and improvement in vision. CONCLUSION: An
      association between optic disk pits and incontinentia pigmenti is presented. The
      case demonstrates the utility of oral acetazolamide in the treatment of serous
      maculopathy associated with optic disk pits.

PMID- 25390183
TI  - Subfoveal choroidal neovascular membrane in the second trimester.
AB  - PURPOSE: To report the experience of treating a woman who presented with a
      subfoveal neovascular membrane during the fifth month of her second pregnancy.
      METHODS: Case report. RESULTS: The visual acuity of the eye 1 month after 1
      intravitreal injection of bevacizumab was 20/30 after the birth of her daughter.
      CONCLUSION: A woman presented with a subfoveal choroidal neovascular membrane
      during the fifth month of her second pregnancy. The decision was made to withhold
      anti-vascular endothelial growth factor therapy until after delivery.

PMID- 25390184
TI  - Comparative study of Gilsanz-Ratib digital atlas and Greulich-Pyle atlas for bone
      age estimation in a Chinese sample.
AB  - BACKGROUND: The applicability of the Gilsanz-Ratib (GR) digital atlas to bone age
      (BA) determination in China has not been evaluated. AIM: To compare the validity
      of GR and the Greulich-Pyle (GP) atlas in BA determination for children in
      Shanghai. SUBJECTS AND METHODS: Left-hand radiographs of 243 girls and 375 boys
      aged 0-13 years were obtained for suspected trauma. They were divided into eight
      sub-groups according to gender and age (0-3, 3-7, 7-10 and 10-13 years).
      Radiographs were read by two radiologists, using both GP and GR atlases. The
      differences between BA and calendar age (CA) were analysed. The inter- and intra
      observer consistency was evaluated. RESULTS: Pearson's correlation coefficients
      indicated a strong positive correlation between methods and between raters. The
      differences between BA and CA of two sub-groups (10-13-year-old boys, GR; 0-3
      year-old girls, GP) were not only statistically significant, but exceeded 1 SD,
      suggesting biological significance. CONCLUSION: Both atlases can be used on most
      age groups. However, the GR atlas is not recommended in boys aged 10-13 years,
      while the GP atlas is not suitable for girls aged 0-3 years. Therefore, the use
      of the GP or GR atlas is practical, depending on the age of the child.

PMID- 25390185
TI  - Modulation of effective connectivity in the default mode network at rest and
      during a memory task.
AB  - It is known that the default mode network (DMN) may be modulated by a cognitive
      task and by performance level. Changes in the DMN have been examined by
      investigating resting-state activation levels, but there have been very few
      studies examining the modulation of effective connectivity of the DMN during a
      task in healthy older subjects. In this study, the authors examined how effective
      connectivity changed in the DMN between rest and during a memory task. The
      authors also investigated whether there was any relationship between effective
      connectivity modulation in the DMN and memory performance, to establish whether
      variations in cognitive performance are related to neural network effective
      connectivity, either at rest or during task performance. Twenty-eight healthy
      older participants underwent a resting-state functional magnetic resonance
      imaging scan and an emotional face-name encoding task. Effective connectivity
      analyses were performed on the DMN to examine the effective connectivity
      modulation in these two different conditions. During the resting state, there was
      strong self-influence in the regions of the DMN, while the main regions with
      statistically significant cross-regional effective connectivity were the
      posterior cingulate cortex (PCC) and the hippocampus (HP). During the memory
      task, the self-influence effective connectivities remained statistically
      significant across the DMN, and there were statistically significant effective
      connectivities from the PCC, HP, amygdala (AM), and parahippocampal region to
      other DMN regions. The authors found that effective connectivities from PCC, HP,
      and AM (in both resting state and during task) were linearly correlated to memory
      performance. The results suggest that superior memory ability in this older
      cohort was associated with effective connectivity both at rest and during the
      memory task of three DMN regions, which are also known to be important for memory
      function.

PMID- 25390186
TI  - Detection of motion artifact patterns in photoplethysmographic signals based on
      time and period domain analysis.
AB  - The presence of motion artifacts in photoplethysmographic (PPG) signals is one of
      the major obstacles in the extraction of reliable cardiovascular parameters in
      continuous monitoring applications. In the current paper we present an algorithm
      for motion artifact detection based on the analysis of the variations in the time
      and the period domain characteristics of the PPG signal. The extracted features
      are ranked using a normalized mutual information feature selection algorithm and
      the best features are used in a support vector machine classification model to
      distinguish between clean and corrupted sections of the PPG signal. The proposed
      method has been tested in healthy and cardiovascular diseased volunteers,
      considering 11 different motion artifact sources. The results achieved by the
      current algorithm (sensitivity--SE: 84.3%, specificity--SP: 91.5% and accuracy-
      ACC: 88.5%) show that the current methodology is able to identify both corrupted
      and clean PPG sections with high accuracy in both healthy (ACC: 87.5%) and
      cardiovascular diseases (ACC: 89.5%) context.

PMID- 25390187
TI  - Ulipristal acetate in the management of symptomatic uterine fibroids: facts and
      pending issues.
AB  - Various treatment options have been proposed for the management of human
      symptomatic uterine fibroids (or myomas). Despite this, the most popular one is
      surgery (myomectomy or hysterectomy). Ulipristal acetate (UA) is a selective
      progesterone receptor modulator. In women programmed for surgical treatment for
      uterine fibroids, oral UA treatment (5 or 10 mg/day) controls symptoms, reduces
      tumor size and improves quality of life as compared to placebo and is not
      inferior to monthly intramuscular injection of leuprolide acetate for 3 months.
      Women treated with up to 4 courses of UA (10 mg/day for 3 months) followed or not
      by norethisterone acetate (10 mg/day for 10 days or placebo) reported a high rate
      of bleeding control, and improved quality of life, pain anxiety and depression.
      Median fibroid volume after successive courses of UA treatment ranged from -63%
      to -72% as compared to baseline value. Endometrium showed benign histological
      changes without hyperplasia, while adverse events were mild or moderate
      throughout the several courses of treatment. There is a need for global cost
      assessment of UA treatment for uterine fibroids, including those women that do
      not reach their expected outcome and need other complementary explorations or
      treatments. Studies are needed in non-Caucasian women, in infertile patients and
      in cases of fibroids associated with adenomyosis. Furthermore, assessment of long
      term UA treatment should include endometrial, cardiocirculatory and neurological
      endpoints. 

PMID- 25390188
TI  - pFPL Vectors for High-Throughput Protein Localization in Fungi: Detecting
      Cytoplasmic Accumulation of Putative Effector Proteins.
AB  - As part of a large-scale project whose goal was to identify candidate effector
      proteins in Magnaporthe oryzae, we developed a suite of vectors that facilitate
      high-throughput protein localization experiments in fungi. These vectors utilize
      Gateway recombinational cloning to place a gene's promoter and coding sequences
      upstream and in frame with enhanced cyan fluorescent protein, green fluorescent
      protein (GFP), monomeric red fluorescence protein (mRFP), and yellow fluorescent
      protein or a nucleus-targeted mCHERRY variant. The respective Gateway cassettes
      were incorporated into Agrobacterium-based plasmids to allow efficient fungal
      transformation using hygromycin or geneticin resistance selection. mRFP proved to
      be more sensitive than the GFP spectral variants for monitoring proteins secreted
      in planta; and extensive testing showed that Gateway-derived fusion proteins
      produced localization patterns identical to their "directly fused" counterparts.
      Use of plasmid for fungal protein localization (pFPL) vectors with two different
      selectable markers provided a convenient way to label fungal cells with different
      fluorescent proteins. We demonstrate the utility of the pFPL vectors for
      identifying candidate effector proteins and we highlight a number of important
      factors that must be taken into consideration when screening for proteins that
      are translocated across the host plasma membrane. 

PMID- 25390189
TI  - Coordinated regulation of arbuscular mycorrhizal fungi and soybean MAPK pathway
      genes improved mycorrhizal soybean drought tolerance.
AB  - Mitogen-activated protein kinase (MAPK) cascades play important roles in the
      stress response in both plants and microorganisms. The mycorrhizal symbiosis
      established between arbuscular mycorrhizal fungi (AMF) and plants can enhance
      plant drought tolerance, which might be closely related to the fungal MAPK
      response and the molecular dialogue between fungal and soybean MAPK cascades. To
      verify the above hypothesis, germinal Glomus intraradices (syn. Rhizophagus
      irregularis) spores and potted experiments were conducted. The results showed
      that AMF GiMAPKs with high homology with MAPKs from Saccharomyces cerevisiae had
      different gene expression patterns under different conditions (nitrogen
      starvation, abscisic acid treatment, and drought). Drought stress upregulated the
      levels of fungi and soybean MAPK transcripts in mycorrhizal soybean roots,
      indicating the possibility of a molecular dialogue between the two symbiotic
      sides of symbiosis and suggesting that they might cooperate to regulate the
      mycorrhizal soybean drought-stress response. Meanwhile, the changes in hydrogen
      peroxide, soluble sugar, and proline levels in mycorrhizal soybean as well as in
      the accelerated exchange of carbon and nitrogen in the symbionts were
      contributable to drought adaptation of the host plants. Thus, it can be
      preliminarily inferred that the interactions of MAPK signals on both sides,
      symbiotic fungus and plant, might regulate the response of symbiosis and, thus,
      improve the resistance of mycorrhizal soybean to drought stress. 

PMID- 25390190
TI  - PII Overexpression in Lotus japonicus Affects Nodule Activity in Permissive Low
      Nitrogen Conditions and Increases Nodule Numbers in High Nitrogen Treated Plants.
AB  - We report here the first characterization of a GLNB1 gene coding for the PII
      protein in leguminous plants. The main purpose of this work was the investigation
      of the possible roles played by this multifunctional protein in nodulation
      pathways. The Lotus japonicus LjGLB1 gene shows a significant transcriptional
      regulation during the light-dark cycle and different nitrogen availability,
      conditions that strongly affect nodule formation, development, and functioning.
      We also report analysis of the spatial profile of expression of LjGLB1 in root
      and nodule tissues and of the protein's subcellular localization. Transgenic L.
      japonicus lines overexpressing the PII protein were obtained and tested for the
      analysis of the symbiotic responses in different conditions. The uncoupling of
      PII from its native regulation affects nitrogenase activity and nodule polyamine
      content. Furthermore, our results suggest the involvement of PII in the signaling
      of the nitrogen nutritional status affecting the legumes' predisposition for
      nodule formation. 

PMID- 25390191
TI  - Bile salts-containing vesicles: promising pharmaceutical carriers for oral
      delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or
      vaccines.
AB  - Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines
      have poor performance after oral administration due to poor solubility or
      degradation in the gastrointestinal tract (GIT). Though, vesicular carriers
      exemplified by liposomes or niosomes can protect the entrapped agent to a certain
      extent from degradation. Nevertheless, the harsh GIT environment exemplified by
      low pH, presence of bile salts and enzymes limits their capabilities by
      destabilizing them. In response to that, more resistant bile salts-containing
      vesicles (BS-vesicles) were developed by inclusion of bile salts into lipid
      bilayers constructs. The effectiveness of orally administrated BS-vesicles in
      improving the performance of vesicles has been demonstrated in researches. Yet,
      these attempts did not gain considerable attention. This is the first review that
      provides a comprehensive overview of utilizing BS-vesicles as a promising
      pharmaceutical carrier with a special focus on their successful applications in
      oral delivery of therapeutic macromolecules and vaccines. Insights on the
      possible mechanisms by which BS-vesicles improve the oral bioavailability of the
      encapsulated drug or immunological response of entrapped vaccine are explained.
      In addition, methods adopted to prepare and characterize BS-vesicles are
      described. Finally, the gap in the scientific researches tackling BS-vesicles
      that needs to be addressed is highlighted. 

PMID- 25390192
TI  - A milk pump as a source for spreading Acinetobacter baumannii in a neonatal
      intensive care unit.
AB  - Acinetobacter baumannii is a Gram-negative coccobacillus that has emerged as a
      troublesome pathogen causing institutional outbreaks. Environmental contamination
      is a distinctive characteristic of this microorganism, which brings a further
      difficulty in infection control. During A. baumannii outbreaks in intensive care
      units, a common contaminated object can be found as a reservoir. Finding out this
      source by epidemiological investigations is of particular importance in order to
      develop effective interventions. We describe an outbreak of A. baumannii and the
      results of epidemiological investigations in a neonatal intensive care unit. The
      outbreak strain was isolated from the outer surface of a breastmilk pump. We have
      successfully controlled the outbreak by careful reviewing of our milk collection
      process.

PMID- 25390193
TI  - Neural correlates of perceived confidence in a partial report paradigm.
AB  - Confidence judgments are often severely distorted: People may feel underconfident
      when responding correctly or, conversely, overconfident in erred responses. Our
      aim here was to identify the timing of brain processes that lead to variations in
      objective performance and subjective judgments of confidence. We capitalized on
      the Partial Report Paradigm [Sperling, G. The information available in brief
      visual presentations. Psychological Monographs: General and Applied, 74, 1,
      1960], which allowed us to separate experimentally the moment of encoding of
      information from that of its retrieval [Zylberberg, A., Dehaene, S., Mindlin, G.
      B., & Sigman, M. Neurophysiological bases of exponential sensory decay and top
      down memory retrieval: A model. Frontiers in Computational Neuroscience, 3,
      2009]. We observed that the level of subjective confidence is indexed by two very
      specific evoked potentials at latencies of about 400 and 600 msec during the
      retrieval stage and by a stationary measure of intensity of the alpha band during
      the encoding period. When factoring out the effect of confidence, objective
      performance shows a weak effect during the encoding and retrieval periods. These
      results have relevant implications for theories of decision-making and
      confidence, suggesting that confidence is not constructed online as evidence is
      accumulated toward a decision. Instead, confidence attributions are more
      consistent with a retrospective mechanism that monitors the entire decision
      process. 

PMID- 25390195
TI  - The impact of musicianship on the cortical mechanisms related to separating
      speech from background noise.
AB  - Musicians have enhanced auditory processing abilities. In some studies, these
      abilities are paralleled by an improved understanding of speech in noisy
      environments, partially due to more robust encoding of speech signals in noise at
      the level of the brainstem. Little is known about the impact of musicianship on
      attention-dependent cortical activity related to lexical access during a speech
      in-noise task. To address this issue, we presented musicians and nonmusicians
      with single words mixed with three levels of background noise, across two
      conditions, while monitoring electrical brain activity. In the active condition,
      listeners repeated the words aloud, and in the passive condition, they ignored
      the words and watched a silent film. When background noise was most intense,
      musicians repeated more words correctly compared with nonmusicians. Auditory
      evoked responses were attenuated and delayed with the addition of background
      noise. In musicians, P1 amplitude was marginally enhanced during active listening
      and was related to task performance in the most difficult listening condition. By
      comparing ERPs from the active and passive conditions, we isolated an N400
      related to lexical access. The amplitude of the N400 was not influenced by the
      level of background noise in musicians, whereas N400 amplitude increased with the
      level of background noise in nonmusicians. In nonmusicians, the increase in N400
      amplitude was related to a reduction in task performance. In musicians only,
      there was a rightward shift of the sources contributing to the N400 as the level
      of background noise increased. This pattern of results supports the hypothesis
      that encoding of speech in noise is more robust in musicians and suggests that
      this facilitates lexical access. Moreover, the shift in sources suggests that
      musicians, to a greater extent than nonmusicians, may increasingly rely on
      acoustic cues to understand speech in noise. 

PMID- 25390194
TI  - Pupillometry as a glimpse into the neurochemical basis of human memory encoding.
AB  - Neurochemical systems are well studied in animal learning; however, ethical
      issues limit methodologies to explore these systems in humans. Pupillometry
      provides a glimpse into the brain's neurochemical systems, where pupil dynamics
      in monkeys have been linked with locus coeruleus (LC) activity, which releases
      norepinephrine (NE) throughout the brain. Here, we use pupil dynamics as a
      surrogate measure of neurochemical activity to explore the hypothesis that NE is
      involved in modulating memory encoding. We examine this using a task-irrelevant
      learning paradigm in which learning is boosted for stimuli temporally paired with
      task targets. We show that participants better recognize images that are paired
      with task targets than distractors and, in correspondence, that pupil size
      changes more for target-paired than distractor-paired images. To further
      investigate the hypothesis that NE nonspecifically guides learning for stimuli
      that are present with its release, a second procedure was used that employed an
      unexpected sound to activate the LC-NE system and induce pupil-size changes;
      results indicated a corresponding increase in memorization of images paired with
      the unexpected sounds. Together, these results suggest a relationship between the
      LC-NE system, pupil-size changes, and human memory encoding. 

PMID- 25390196
TI  - Structural similarity exerts opposing effects on perceptual differentiation and
      categorization: an FMRI study.
AB  - We manipulated the degree of structural similarity between objects that had to be
      matched either according to whether they represented the same object (perceptual
      matching) or belonged to the same category (conceptual matching). Behaviorally,
      performance improved as a linear function of increased structural similarity
      during conceptual matching but deteriorated as a linear function of increased
      structural similarity during perceptual matching. These effects were mirrored in
      fMRI recordings where activation in several ventral posterior areas exhibited a
      similar interaction between match type and structural similarity. Our findings
      provide direct support for the notion that structural similarity exerts opposing
      effects on classification depending on whether objects are to be perceptually
      differentiated or categorized-a notion that has been based on rather
      circumstantial evidence. In particular, the finding that structural similarity
      plays a major role in categorization of instances according to taxonomy
      challenges the view that the organization of superordinate categories is not
      driven by shared structural features. 

PMID- 25390197
TI  - Variable left-hemisphere language and orthographic lateralization reduces right
      hemisphere face lateralization.
AB  - It is commonly believed that, in right-handed individuals, words and faces are
      processed by distinct neural systems: one in the left hemisphere (LH) for words
      and the other in the right hemisphere (RH) for faces. Emerging evidence suggests,
      however, that hemispheric selectivity for words and for faces may not be
      independent of each other. One recent account suggests that words become
      lateralized to the LH to interact more effectively with language regions, and
      subsequently, as a result of competition with words for representational space,
      faces become lateralized to the RH. On this interactive account, left-handed
      individuals, who as a group show greater variability with respect to hemispheric
      language dominance, might be expected to show greater variability in their degree
      of RH lateralization of faces as well. The current study uses behavioral measures
      and ERPs to compare the hemispheric specialization for both words and faces in
      right- and left-handed adult individuals. Although both right- and left-handed
      groups demonstrated LH over RH superiority in discrimination accuracy for words,
      only the right-handed group demonstrated RH over LH advantage in discrimination
      accuracy for faces. Consistent with this, increased right-handedness was related
      to an increase in RH superiority for face processing, as measured by the strength
      of the N170 ERP component. Interestingly, the degree of RH behavioral superiority
      for face processing and the amplitude of the RH N170 for faces could be predicted
      by the magnitude of the N170 ERP response to words in the LH. These results are
      discussed in terms of a theoretical account in which the typical RH face
      lateralization fails to emerge in individuals with atypical language
      lateralization because of weakened competition from the LH representation of
      words. 

PMID- 25390199
TI  - Theta oscillations modulate attentional search performance periodically.
AB  - Visual search--finding a target element among similar-looking distractors--is one
      of the prevailing experimental methods to study attention. Current theories of
      visual search postulate an early stage of feature extraction interacting with an
      attentional process that selects candidate targets for further analysis; in
      difficult search situations, this selection is iterated until the target is
      found. Although such theories predict an intrinsic periodicity in the neuronal
      substrates of attentional search, this prediction has not been extensively tested
      in human electrophysiology. Here, using EEG and TMS, we study attentional
      periodicities in visual search. EEG measurements indicated that successful and
      unsuccessful search trials were associated with different amounts of poststimulus
      oscillatory amplitude and phase-locking at ~6 Hz and opposite prestimulus
      oscillatory phase at ~6 Hz. A trial-by-trial comparison of pre- and poststimulus
      ~6 Hz EEG phases revealed that the functional interplay between prestimulus brain
      states, poststimulus oscillations, and successful search performance was mediated
      by a partial phase reset of ongoing oscillations. Independently, TMS applied over
      occipital cortex at various intervals after search onset demonstrated a periodic
      pattern of interference at ~6 Hz. The converging evidence from independent TMS
      and EEG measurements demonstrates that attentional search is modulated
      periodically by brain oscillations. This periodicity is naturally compatible with
      a sequential exploration by attention, although a parallel but rhythmically
      modulated attention spotlight cannot be entirely ruled out.

PMID- 25390198
TI  - Value is in the eye of the beholder: early visual cortex codes monetary value of
      objects during a diverted attention task.
AB  - A central concern in the study of learning and decision-making is the
      identification of neural signals associated with the values of choice
      alternatives. An important factor in understanding the neural correlates of value
      is the representation of the object itself, separate from the act of choosing. Is
      it the case that the representation of an object within visual areas will change
      if it is associated with a particular value? We used fMRI adaptation to measure
      the neural similarity of a set of novel objects before and after participants
      learned to associate monetary values with the objects. We used a range of both
      positive and negative values to allow us to distinguish effects of behavioral
      salience (i.e., large vs. small values) from effects of valence (i.e., positive
      vs. negative values). During the scanning session, participants made a perceptual
      judgment unrelated to value. Crucially, the similarity of the visual features of
      any pair of objects did not predict the similarity of their value, so we could
      distinguish adaptation effects due to each dimension of similarity. Within early
      visual areas, we found that value similarity modulated the neural response to the
      objects after training. These results show that an abstract dimension, in this
      case, monetary value, modulates neural response to an object in visual areas of
      the brain even when attention is diverted. 

PMID- 25390200
TI  - Acoustic detail guides attention allocation in a selective listening task.
AB  - The flexible allocation of attention enables us to perceive and behave
      successfully despite irrelevant distractors. How do acoustic challenges influence
      this allocation of attention, and to what extent is this ability preserved in
      normally aging listeners? Younger and healthy older participants performed a
      masked auditory number comparison while EEG was recorded. To vary selective
      attention demands, we manipulated perceptual separability of spoken digits from a
      masking talker by varying acoustic detail (temporal fine structure). Listening
      conditions were adjusted individually to equalize stimulus audibility as well as
      the overall level of performance across participants. Accuracy increased, and
      response times decreased with more acoustic detail. The decrease in response
      times with more acoustic detail was stronger in the group of older participants.
      The onset of the distracting speech masker triggered a prominent contingent
      negative variation (CNV) in the EEG. Notably, CNV magnitude decreased
      parametrically with increasing acoustic detail in both age groups. Within
      identical levels of acoustic detail, larger CNV magnitude was associated with
      improved accuracy. Across age groups, neuropsychological markers further linked
      early CNV magnitude directly to individual attentional capacity. Results
      demonstrate for the first time that, in a demanding listening task, instantaneous
      acoustic conditions guide the allocation of attention. Second, such basic neural
      mechanisms of preparatory attention allocation seem preserved in healthy aging,
      despite impending sensory decline. 

PMID- 25390201
TI  - Valence asymmetries in the human amygdala: task relevance modulates amygdala
      responses to positive more than negative affective cues.
AB  - Organisms must constantly balance appetitive needs with vigilance for potential
      threats. Recent research suggests that the amygdala may play an important role in
      both of these goals. Although the amygdala plays a role in processing
      motivationally relevant stimuli that are positive or negative, negative
      information often appears to carry greater weight. From a functional perspective,
      this may reflect the fact that threatening stimuli generally require action,
      whereas appetitive stimuli can often be safely ignored. In this study, we examine
      whether amygdala activation to positive stimuli may be more sensitive to task
      goals than negative stimuli, which are often related to self-preservation
      concerns. During fMRI, participants were presented with two images that varied on
      valence and extremity and were instructed to focus on one of the images. Results
      indicated that negative stimuli elicited greater amygdala activity regardless of
      task relevance. In contrast, positive stimuli only led to a relative increase in
      amygdala activity when they were task relevant. This suggests that the amygdala
      may be more responsive to negative stimuli regardless of their relevance to
      immediate goals, whereas positive stimuli may only elicit amygdala activity when
      they are relevant to the perceivers' goals. This pattern of valence asymmetry in
      the human amygdala may help balance approach-related goal pursuit with chronic
      self-preservation goals. 

PMID- 25390202
TI  - Tolerance of macaque middle STS body patch neurons to shape-preserving stimulus
      transformations.
AB  - Functional imaging studies in human and nonhuman primates have demonstrated
      regions in the brain that show category selectivity for faces or (headless)
      bodies. Recent fMRI-guided single unit studies of the macaque face category
      selective regions have increased our understanding of the response properties of
      single neurons in these face patches. However, much less is known about the
      response properties of neurons in the fMRI-defined body category-selective
      regions ("body patches"). Recently, we reported that the majority of single
      neurons in one fMRI-defined body patch, the mid-STS body patch, responded more
      strongly to bodies compared with other objects. Here we assessed the tolerance of
      these neurons' responses and stimulus preference for shape-preserving image
      transformations. After mapping the receptive field of the single neurons, we
      found that their stimulus preference showed a high degree of tolerance for
      changes in the position and size of the stimulus. However, their response
      strongly depended on the in-plane orientation of a body. The selectivity of most
      neurons was, to a large degree, preserved when silhouettes were presented instead
      of the original textured and shaded images, suggesting that mainly shape-based
      features are driving these neurons. In a human psychophysical study, we showed
      that the information present in silhouettes is largely sufficient for body versus
      nonbody categorization. These data suggest that mid-STS body patch neurons
      respond predominantly to oriented shape features that are prevalent in images of
      bodies. Their responses can inform position- and retinal size-invariant body
      categorization and discrimination based on shape. 

PMID- 25390203
TI  - Sensitivity to object impossibility in the human visual cortex: evidence from
      functional connectivity.
AB  - Processing spatial configuration is a fundamental requirement for object
      recognition. Using fMRI, the neural basis underlying this ability was examined
      while human participants viewed possible and visually similar, but spatially
      impossible, objects presented for either long or short exposure duration.
      Response profiles in object-selective cortical regions exhibited sensitivity to
      object possibility, but only for the long exposure duration. Contrary, functional
      connectivity, indexed by the pairwise correlations between activation profiles
      across ROIs, revealed sensitivity to possibility, evident in enhanced
      correlations for impossible compared with possible objects. Such sensitivity was
      found even following a brief exposure duration, which allowed only minimal
      awareness of possibility. Importantly, this sensitivity was correlated with
      participants' general spatial ability as assessed by an independent
      neuropsychological test. These results suggest that the visual system is highly
      susceptible to objects' 3-D structural information even with minimal perceptual
      awareness. Such sensitivity is captured at the level of functional connectivity
      between object-selective regions, rather than the absolute level of within-region
      activity, implicating the role of interregional synchronization in the
      representation of objects' 3-D structure. 

PMID- 25390204
TI  - When imagining yourself in pain, visual perspective matters: the neural and
      behavioral correlates of simulated sensory experiences.
AB  - Via mental simulation, imagined events faithfully reproduce the neural and
      behavioral activities that accompany their actual occurrence. However, little is
      known about how fundamental characteristics of mental imagery-notably
      perspectives of self-shape neurocognitive processes. To address this issue, we
      used fMRI to explore the impact that vantage point exerts on the neural and
      behavioral correlates of imaginary sensory experiences (i.e., pain). Participants
      imagined painful scenarios from three distinct visual perspectives: first-person
      self (1PS), third-person self (3PS), and third-person other (3PO). Corroborating
      increased ratings of pain and embodiment, 1PS (cf. 3PS) simulations elicited
      greater activity in the right anterior insula, a brain area that supports
      interoceptive and emotional awareness. Additionally, 1PS simulations evoked
      greater activity in brain areas associated with visual imagery and the sense of
      body ownership. Interestingly, no differences were observed between 3PS and 3PO
      imagery. Taken together, these findings reveal the neural and behavioral
      correlates of visual perspective during mental simulation. 

PMID- 25390205
TI  - Recollection and familiarity exhibit dissociable similarity gradients: a test of
      the complementary learning systems model.
AB  - Memory can often be triggered by retrieval cues that are quite different from the
      originally encoded events, but how different memory processes respond to
      variations in cue-target similarity is poorly understood. We begin by presenting
      simulations using a neurocomputational model of recognition memory (i.e., the
      complementary learning systems model), which proposes that the hippocampus
      supports recollection of associative information whereas the surrounding cortex
      supports assessments of item familiarity. The simulations showed that increases
      in the similarity between retrieval cues and learned items led to relatively
      linear increases in a cortex-based memory signal but led to steeper and more
      thresholded increases in the hippocampal signal. We then tested the predictions
      of the model by examining the effects of varying cue-target similarity in two
      recognition memory experiments in which participants studied a list of computer
      generated faces and then, at test, gave confidence and remember/know responses to
      morphed faces. In both experiments, as cue-target similarity was increased,
      familiarity-based recognition increased in a gradual and relatively linear
      fashion, whereas recollection showed significantly steeper gradients. The results
      show that recollection and familiarity exhibit distinct similarity functions in
      recognition memory that correspond with predicted retrieval dynamics of the
      hippocampus and cortex, respectively. 

PMID- 25390206
TI  - Patterns of modulation in the activity and connectivity of motor cortex during
      the repeated generation of movement sequences.
AB  - It is not clear how the engagement of motor mnemonic processes is expressed in
      online brain activity. We scanned participants, using fMRI, during the paced
      performance of a finger-to-thumb opposition sequence (FOS), intensively trained a
      day earlier (T-FOS), and a similarly constructed, but novel, untrained FOS (U
      FOS). Both movement sequences were performed in pairs of blocks separated by a
      brief rest interval (30 sec). We have recently shown that in the primary motor
      cortex (M1) motor memory was not expressed in the average signal intensity but
      rather in the across-block signal modulations, that is, when comparing the first
      to the second performance block across the brief rest interval. Here, using an M1
      seed, we show that for the T-FOS, the M1-striatum functional connectivity
      decreased across blocks; however, for the U-FOS, connectivity within the M1 and
      between M1 and striatum increased. In addition, in M1, the pattern of within
      block signal change, but not signal variability per se, reliably differentiated
      the two sequences. Only for the U-FOS and only within the first blocks in each
      pair, the signal significantly decreased. No such modulation was found within the
      second corresponding blocks following the brief rest interval in either FOS. We
      propose that a network including M1 and striatum underlies online motor working
      memory. This network may promote a transient integrated representation of a new
      movement sequence and readily retrieves a previously established movement
      sequence representation. Averaging over single events or blocks may not capture
      the dynamics of motor representations that occur over multiple timescales. 

PMID- 25390207
TI  - The attentional blink impairs detection and delays encoding of visual
      information: evidence from human electrophysiology.
AB  - This article explores the time course of the functional interplay between
      detection and encoding stages of information processing in the brain and the role
      they play in conscious visual perception. We employed a multitarget rapid serial
      visual presentation (RSVP) approach and examined the electrophysiological P3
      component elicited by a target terminating an RSVP sequence. Target-locked P3
      activity was detected both at frontal and parietal recording sites and an
      independent component analysis confirmed the presence of two distinct P3
      components. The posterior P3b varied with intertarget lag, with diminished
      amplitude and postponed latency at short relative to long lags-an
      electroencephalographic signature of the attentional blink (AB). Under analogous
      conditions, the anterior P3a was also reduced in amplitude but did not vary in
      latency. Collectively, the results provide an electrophysiological record of the
      interaction between frontal and posterior components linked to detection (P3a)
      and encoding (P3b) of visual information. Our findings suggest that, although the
      AB delays target encoding into working memory, it does not slow down detection of
      a target but instead reduces the efficacy of this process. A functional
      characterization of P3a in attentive tasks is discussed with reference to current
      models of the AB phenomenon. 

PMID- 25390208
TI  - Superfluous neuroscience information makes explanations of psychological
      phenomena more appealing.
AB  - Does the presence of irrelevant neuroscience information make explanations of
      psychological phenomena more appealing? Do fMRI pictures further increase that
      allure? To help answer these questions, 385 college students in four experiments
      read brief descriptions of psychological phenomena, each one accompanied by an
      explanation of varying quality (good vs. circular) and followed by superfluous
      information of various types. Ancillary measures assessed participants'
      analytical thinking, beliefs on dualism and free will, and admiration for
      different sciences. In Experiment 1, superfluous neuroscience information
      increased the judged quality of the argument for both good and bad explanations,
      whereas accompanying fMRI pictures had no impact above and beyond the
      neuroscience text, suggesting a bias that is conceptual rather than pictorial.
      Superfluous neuroscience information was more alluring than social science
      information (Experiment 2) and more alluring than information from prestigious
      "hard sciences" (Experiments 3 and 4). Analytical thinking did not protect
      against the neuroscience bias, nor did a belief in dualism or free will. We
      conclude that the "allure of neuroscience" bias is conceptual, specific to
      neuroscience, and not easily accounted for by the prestige of the discipline. It
      may stem from the lay belief that the brain is the best explanans for mental
      phenomena. 

PMID- 25390209
TI  - The Photophysics of Three Naphthylmethylene Malononitriles.
AB  - The solvent dependence of the photophysical properties of three naphthylmethylene
      malononitriles, 1-(1-naphthalenylmethylene)-propanedinitrile (1-MN), 2-(2
      naphthalenylmethylene)-propanedinitrile (2-MN), and 2-(3,4-dihydro-1(2H)
      phenanthrenylidene)-propanedinitile (r2-MN), was studied in order to determine
      their potential utility as fluidity probes and to make comparisons to the better
      studied benzylidene malononitriles. Density functional calculations were used to
      understand the possible conformational states related to rotation about the vinyl
      aromatic bond ("tau"). Absorption and emission frequencies, extinction
      coefficients, fluorescence quantum yields, and fluorescence lifetimes were
      measured in 11 representative solvents. Both the computational and experimental
      results indicate that the S0 -> S1 transitions of these molecules have
      substantial charge-transfer character and produce highly polar excited states.
      Emission appears to result from relaxed S1 states which do not differ
      qualitatively from the Franck-Condon states reached by absorption. In 2-MN, time
      resolved emission reveals the presence of two ground-state conformers ("a" and
      "b" differing by ~180 degrees  rotation about tau) coexisting in low-polarity
      solvents. In contrast, 1-MN appears to exist primarily as a single dominant
      ground-state conformer. Fluorescence lifetimes vary from ~1 ps in 1-MN to ~200 ps
      in 2-MN(a) at room temperature. With the exception of 2-MN(a), the lifetimes vary
      systematically with solvent in a manner similar to what is observed in the
      benzylidene malononitriles. Both solvent polarity and fluidity appear to be
      important determinants of lifetime. The primary mechanism of fluorescence decay
      in naphthylmethylene malononitriles is likely to be the same as that of the
      benzylidene malononitriles-twisting about the double bond in S1, which leads to
      rapid internal conversion via a conical intersection with S0. 

PMID- 25390210
TI  - Bioassay-guided isolation and identification of bioactive compound from aerial
      parts of Luffa acutangula against lung cancer cell line NCI-H460.
AB  - Luffa acutangula (Cucurbitaceae) is widely used as a traditional medicine in
      India and was reported to possess various pharmacological activities including
      its anti-proliferative effects. In this study, the bioactive compound of
      ethanolic extract of L. acutangula (LA) was isolated using bioassay-guided
      approach. Five major fractions were collected and evaluated for their anti
      proliferative activity against non-small cell lung cancer cells (NCI-H460). Among
      the test fractions, the fraction LA/FII effectively decreased the growth of
      cancer cells with IC50 values of 10 ug/ml concentration. Furthermore, it
      significantly increased intracellular reactive oxygen species and decreased the
      mitochondrial membrane potential. The apoptogenic activity of fraction LA/FII was
      confirmed by cell shrinkage, membrane blebbing and formation of apoptotic bodies.
      A single bioactive compound was isolated from the active faction, LA/FII and
      subsequently identified as 1,8 dihydroxy-4-methylanthracene 9,10-dione (compound
      1) by comparing its spectral data [Ultraviolet (UV), Infrared (IR), Nuclear
      magnetic resonance (NMR) and Electrospray Ionization-Mass Spectroscopy (ESI-MS)]
      with literature values. This is the first report on the isolation of compound 1
      from this plant. 

PMID- 25390211
TI  - Ultrasound in rare diffuse liver disease.
AB  - Ultrasound is often the first imaging procedure performed in the evaluation of
      individuals with suspected or known liver disease. Despite technical advances in
      ultrasound techniques, sonographic detection and evaluation of diffuse liver
      disease still remains difficult. This is due to the fact that diffuse liver
      disease does not always cause distortion of the liver parenchymal texture,
      internal liver architecture, or shape of the liver. On the other hand, the size
      of the liver, the echo pattern of the hepatic parenchyma, the analysis of
      intrahepatic vessels and alterations in perihepatic structures and lymph nodes
      can be helpful sonographic parameters of diffuse liver disease. Until now, the
      sonographic appearance of some rare diffuse liver diseases is not well known.
      However, there are some typical sonomorphological signs that, once identified,
      can facilitate the differentiation between various diseases. The aim of this
      paper is to highlight some typical ultrasound findings of liver parenchyma and
      perihepatic lymph node structures in rare diffuse liver diseases based on a
      review of published data. 

PMID- 25390212
TI  - New economic training model for installing ultrasound-guided drainages.
AB  - Abscesses and circumscribed collections of fluid are frequently found as
      complications of infectious diseases or surgery. Drainage is often indicated. We
      have established a new, economic, easy-to-make model to learn and improve
      competence in installing ultrasound-guided drainage. Up to fifteen water balloons
      (size 30 - 50 mm) were placed in a plastic box which then was filled with instant
      custard powder mixed with water. Spiral computed tomography (CT) of this box was
      performed. Experienced (n = 8) and inexperienced examiners (n = 8) drained the
      balloons via a direct puncture technique using either ultrasound-guidance alone
      or volume navigation with image fusion (ultrasound and CT) with needle tracking.
      Trainees filled out a questionnaire (before and after training) asking for
      information on their experience in ultrasound, in installing drainages and
      evaluating the new model. The time needed for installing the drainage was
      measured. None of the participants had ever attended a course on drainage
      installation. Only a few of the experienced examiners (n = 3) would autonomously
      install a drainage into a fluid collection with a size exceeding 4 cm before
      training. After training all participants felt more confident in ultrasound and
      in installing drainages into abscesses or other fluid collections. Most of the
      participants rated additional volume navigation with image fusion as a helpful
      tool. Ultrasound-guided drainage of abscesses can be trained easily with this new
      and economic model. Students and physicians can improve their skills and gain
      confidence in performing ultrasound-guided interventions.

PMID- 25390213
TI  - Chronic pancreatitis with hemosuccus pancreaticus. The diagnostic contribution of
      computed tomography and contrast enhanced ultrasonography--case report.
AB  - Hemosuccus pancreaticus is defined as upper gastrointestinal hemorrhage from the
      ampulla of Vater via the pancreatic duct. It is a rare disease, with non-specific
      presentation, challenging to diagnose and difficult to treat, with high mortality
      rates in untreated patients with massive bleeding. Given the intermittent nature
      of the bleeding, delays in diagnosis frequently occur. Timely diagnosis and
      treatment seem to result in markedly reduced mortality, therefore we emphasize
      the diagnostic contribution of imaging techniques by presenting the case of a
      patient with chronic pancreatitis in whom computed tomography established the
      diagnosis of blood in the Wirsung duct and contrast-enhanced ultrasound brought
      its added value by excluding the active bleeding. 

PMID- 25390214
TI  - Ultrasound contrast agents for ultrasound molecular imaging.
AB  - Ultrasound is a real-time imaging technique which is widely used in many clinical
      applications for its capacity to provide anatomic information with high spatial
      and temporal resolution. The advent of ultrasound contrast agents in combination
      with contrast-specific imaging modes has given access to perfusion assessments at
      an organ level, leading to an improved diagnostic accuracy. More recently, the
      development of biologically-targeted ultrasound contrast agents has expanded the
      role of ultrasound even further into molecular imaging applications. Ultrasound
      molecular imaging can be used to visualize the expression of intravascular
      markers, and to assess their local presence over time and/or during therapeutic
      treatment. Major applications are in the field of inflammation and
      neoangiogenesis due to the strictly intravascular presence of microbubbles.
      Various technologies have been investigated for attaching the targeting moiety to
      the shell from simple biotin-avidin constructs to more elaborated insertion
      within the shell through attachment to PEG residues. This important improvement
      has allowed a clinical translation of initial pre-clinical investigations,
      opening the way for an early detection and an accurate characterization of
      lesions in patients. The combination of anatomic, functional and molecular
      information/data provided by contrast ultrasound is a powerful tool which is
      still in its infancy due to the lack of agents suitable for clinical use. The
      advantages of ultrasound techniques combined with the molecular signature of
      lesions will represent a significant advance in imaging in the field of
      personalized medicine. 

PMID- 25390215
TI  - [Fiber, food intolerances, FODMAPs, gluten and functional gastrointestinal
      disorders--update 2014].
AB  - The controversial effects of dietary fiber on symptoms in functional
      gastrointestinal disorders are summarized. Studies concerning adverse reaction to
      foods are mentioned and the possible role of food allergy and food intolerances,
      especially pseudoallergic reactions to biogenes amines, in symptom provocation is
      discussed. The known effects of lactose deficiency and fructose malabsorption are
      reviewed. The FODMAP concept (fermentable oligo-, di-, monosaccharides and
      polyols) is presented in more detail and recent studies on pathophysiological
      effects of FODMAP constituents and of therapeutic effects of a low FODMAP diet on
      symptoms in patients with irritable bowel syndrome are discussed. Finally,
      studies on the new disorder non-celiac gluten sensitivity (NCGS) are summarized
      and the state of the discussion whether wheat intolerance is due to gluten or the
      grains is given. 

PMID- 25390216
TI  - [S2k guideline: gastroesophageal reflux disease guided by the German Society of
      Gastroenterology: AWMF register no. 021-013].

PMID- 25390217
TI  - [Conventional US, US elasticity imaging and acoustic radiation force impulse
      imaging for prediction of malignancy in thyroid nodules].

PMID- 25390218
TI  - A case for the case.

PMID- 25390219
TI  - Photodynamic therapy with verteporfin for serpiginous choroiditis with subfoveal
      choroidal neovascularization.

PMID- 25390220
TI  - Choroidal neovascularization associated with goldmann-favre syndrome.

PMID- 25390221
TI  - Is "lupus choroidopathy" secondary to corticosteroid-induced central serous
      chorioretinopathy?

PMID- 25390222
TI  - Systemic and ocular manifestations of catastrophic antiphospholipid syndrome: a
      case report.

PMID- 25390223
TI  - Sustained response to multiple intravitreal triamcinolone acetonide injections in
      a patient with predominantly occult choroidal neovascularization.

PMID- 25390224
TI  - Management of papillophlebitis associated cystoid macular edema with intravitreal
      triamcinolone acetonide: a case report.

PMID- 25390225
TI  - Coxiella burnetii infection, a potential cause of neuroretinitis-two case reports
      and literature review.

PMID- 25390226
TI  - Neurosensory macular detachment in group 2a juxtafoveolar telangiectasis and
      resolution following intravitreal triamcinolone.

PMID- 25390227
TI  - Frontal linear scleroderma (en coup de sabre) associated with central serous
      chorioretinopathy.

PMID- 25390228
TI  - Four-generation familial benign fleck retina.

PMID- 25390229
TI  - Endogenous endophthalmitis presenting as a choroidal abscess in a healthy
      individual.

PMID- 25390230
TI  - Failure of immunotherapy and chemotherapy for a patient with primary choroidal
      melanoma.

PMID- 25390231
TI  - Adult optic nerve glioma presenting as central retinal vein occlusion.

PMID- 25390232
TI  - Melanocytoma of the choroid: 29-year follow-up.

PMID- 25390233
TI  - Choroidal melanoma in a patient with oculocutaneous albinoidism.

PMID- 25390235
TI  - Ten-year follow-up of retained subfoveal perfluoro-N-octane liquid.

PMID- 25390234
TI  - Latanoprost induced iritis after vitrectomy surgery.

PMID- 25390236
TI  - Pneumatic retinopexy for primary repair of rhegmatogenous retinal detachment in
      marfan syndrome.

PMID- 25390237
TI  - Anterior ischemic syndrome and band extrusion after scleral buckling.

PMID- 25390238
TI  - Evolution and spontaneous regression of photoreceptor disruption secondary to
      posterior vitreous detachment: optical coherence tomography features.

PMID- 25390239
TI  - Macular exudation as the presenting feature of acute retinal necrosis syndrome.

PMID- 25390240
TI  - Immune recovery uveitis in a CMV retinitis patient without hiv infection.

PMID- 25390241
TI  - Severe uveitis successfully treated with leflunomide.

PMID- 25390244
TI  - Graduating to better health: "Schoolies" without hangovers.

PMID- 25390242
TI  - Self-digitization microfluidic chip for absolute quantification of mRNA in single
      cells.
AB  - Quantification of mRNA in single cells provides direct insight into how
      intercellular heterogeneity plays a role in disease progression and outcomes.
      Quantitative polymerase chain reaction (qPCR), the current gold standard for
      evaluating gene expression, is insufficient for providing absolute measurement of
      single-cell mRNA transcript abundance. Challenges include difficulties in
      handling small sample volumes and the high variability in measurements.
      Microfluidic digital PCR provides far better sensitivity for minute quantities of
      genetic material, but the typical format of this assay does not allow for
      counting of the absolute number of mRNA transcripts samples taken from single
      cells. Furthermore, a large fraction of the sample is often lost during sample
      handling in microfluidic digital PCR. Here, we report the absolute quantification
      of single-cell mRNA transcripts by digital, one-step reverse transcription PCR in
      a simple microfluidic array device called the self-digitization (SD) chip. By
      performing the reverse transcription step in digitized volumes, we find that the
      assay exhibits a linear signal across a wide range of total RNA concentrations
      and agrees well with standard curve qPCR. The SD chip is found to digitize a high
      percentage (86.7%) of the sample for single-cell experiments. Moreover,
      quantification of transferrin receptor mRNA in single cells agrees well with
      single-molecule fluorescence in situ hybridization experiments. The SD platform
      for absolute quantification of single-cell mRNA can be optimized for other genes
      and may be useful as an independent control method for the validation of mRNA
      quantification techniques. 

PMID- 25390245
TI  - Safety and effectiveness of influenza vaccines.

PMID- 25390246
TI  - The health of "emerging adults" in Australia: freedom, risk and rites of passage.

PMID- 25390249
TI  - Rural patients travel for health care.

PMID- 25390250
TI  - Getting the levers right: a way forward for rural medicine.

PMID- 25390251
TI  - Medical tourism raises questions that highlight the need for care and caution.

PMID- 25390252
TI  - The 4th Rural and Remote Health Scientific Symposium.

PMID- 25390253
TI  - Should the legal age for buying alcohol be raised to 21 years?

PMID- 25390254
TI  - Should the legal age for buying alcohol be raised to 21 years? In Reply.

PMID- 25390255
TI  - Anomalous warning labels on alcoholic energy drink cans.

PMID- 25390256
TI  - Leaving judgement at the door.

PMID- 25390257
TI  - The health impacts of the 2018 Gold Coast Commonwealth Games: proactive planning
      is required, but who will do this?

PMID- 25390258
TI  - Rural clinical school outcomes: what is success and how long do we wait for it?

PMID- 25390259
TI  - Rural clinical school outcomes: what is success and how long do we wait for it?
      In reply.

PMID- 25390260
TI  - Aboriginal and Torres Strait Islander medical students' and doctors' career
      intentions.

PMID- 25390261
TI  - Newborn bloodspot screening: setting the Australian national policy agenda.

PMID- 25390262
TI  - Cytomegalovirus disease in immunocompetent adults.
AB  - Cytomegalovirus (CMV) is a highly prevalent and globally distributed virus. CMV
      infection in healthy adults is usually asymptomatic or causes a mild
      mononucleosis-like syndrome. CMV disease causes significant morbidity and
      mortality in neonates and severely immunocompromised adults. CMV disease can
      present with a wide range of manifestations, with colitis being the most common.
      The incidence of severe CMV disease in immunocompetent adults appears to be
      greater than previously thought, which may be partly due to immune dysfunction
      related to comorbidities such as kidney disease or diabetes mellitus. CMV disease
      can mimic an array of alternative diagnoses and pose a significant diagnostic
      challenge, especially in immunocompetent adults, leading to delayed diagnosis,
      adverse health outcomes and unnecessary financial expense. Non-invasive testing
      for CMV is widely available and can facilitate early diagnosis if used
      appropriately. Although limited, current evidence suggests that targeted
      antiviral therapy with ganciclovir or valganciclovir is appropriate for severe
      CMV disease in immunocompetent adults. 

PMID- 25390263
TI  - The global response to diabetes: action or apathy?
AB  - Diabetes and related non-communicable diseases (NCDs) account for over 60% of the
      world's annual deaths, untold personal suffering, and an economically crippling
      burden of lost productivity. Despite the body of evidence and various calls to
      action, historically, the global response has bordered on apathy. Although
      diabetes and related NCDs remain disproportionately underfunded, the United
      Nations now recognises them as a major challenge to human and economic
      development, resulting in an action-oriented policy, frameworks and monitoring
      requirements that are being driven by the UN and the World Health Organization.
      Australia is at the forefront of many of these initiatives and is currently
      developing a new national diabetes strategy. 

PMID- 25390264
TI  - Survey of alcohol-related presentations to Australasian emergency departments.
AB  - OBJECTIVE: To determine the proportion of alcohol-related presentations to
      emergency departments (EDs) in Australia and New Zealand, at a single time point
      on a weekend night shift. DESIGN, SETTING AND PARTICIPANTS: A point prevalence
      survey of ED patients either waiting to be seen or currently being seen conducted
      at 02:00 local time on 14 December 2013 in 106 EDs in Australia and New Zealand.
      MAIN OUTCOME MEASURES: The number of ED presentations that were alcohol-related,
      defined using World Health Organization ICD-10 codes. RESULTS: At the 106
      hospitals (92 Australia, 14 New Zealand) that provided data, 395 (14.3%; 95% CI,
      13.0%-15.6%) of 2766 patients in EDs at the study time were presenting for
      alcohol-related reasons; 13.8% (95% CI, 12.5%-15.2%) in Australia and 17.9% (95%
      CI, 13.9%-22.8%) in New Zealand. The distribution was skewed left, with
      proportions ranging from 0 to 50% and a median of 12.5%. Nine Australian
      hospitals and one New Zealand hospital reported that more than a third of their
      ED patients had alcohol-related presentations; the Northern Territory (38.1%) and
      Western Australia (21.1%) reported the highest proportions of alcohol-related
      presentations. CONCLUSIONS: One in seven ED presentations in Australian and New
      Zealand at this 02:00 snapshot were alcohol-related, with some EDs seeing more
      than one in three alcohol-related presentations. This confirms that alcohol
      related presentations to EDs are currently underreported and makes a strong case
      for public health initiatives.

PMID- 25390265
TI  - "After-hours" staffing of trauma centres and outcomes among patients presenting
      with acute traumatic coagulopathy.
AB  - OBJECTIVE: To examine the effect of the "after-hours" (18:00-07:00) model of
      trauma care on a high-risk subgroup - patients presenting with acute traumatic
      coagulopathy (ATC). DESIGN, PARTICIPANTS AND SETTING: Retrospective analysis of
      data from the Alfred Trauma Registry for patients with ATC presenting between 1
      January 2006 and 31 December 2011. MAIN OUTCOME MEASURE: Mortality at hospital
      discharge, adjusted for potential confounders, describing the association between
      after-hours presentation and mortality. RESULTS: There were 398 patients with ATC
      identified during the study period, of whom 197 (49.5%) presented after hours.
      Mortality among patients presenting after hours was 43.1%, significantly higher
      than among those presenting in hours (33.1%; P = 0.04). Following adjustment for
      possible confounding variables of age, presenting Glasgow Coma Scale score,
      urgent surgery or angiography and initial base deficit, after-hours presentation
      was significantly associated with higher mortality at hospital discharge
      (adjusted odds ratio, 1.77; 95% CI, 1.10-2.87). CONCLUSION: The after-hours model
      of care was associated with worse outcomes among some of the most critically ill
      trauma patients. Standardising patient reception at major trauma centres to
      ensure a consistent level of care across all hours of the day may improve
      outcomes among patients who have had a severe injury.

PMID- 25390266
TI  - The effect of obesity on pregnancy outcomes among Australian Indigenous and non
      Indigenous women.
AB  - OBJECTIVE: To assess whether the effect of pre-pregnancy overweight or obesity on
      maternal complications and perinatal outcomes is modified by Indigenous status.
      DESIGN, PARTICIPANTS AND SETTING: Population-based study using de-identified
      aggregate data on pregnancies resulting in singleton births from Indigenous (n =
      13 582) and non-Indigenous (n = 241 270) women from the Queensland Perinatal Data
      Collection, 1 July 2007 to 31 December 2011. MAIN OUTCOME MEASURES: Prevalence of
      maternal (gestational diabetes mellitus [GDM], hypertensive disorders of
      pregnancy [HDP]) and delivery (preterm birth, birthweight, Apgar score) outcomes
      by Indigenous status and their association with pre-pregnancy body mass index.
      RESULTS: In 57% of Indigenous pregnancies and 49% of non-Indigenous pregnancies,
      the mother was overweight, obese or severely obese. Prevalences of GDM, preterm
      birth and low birthweight were higher in Indigenous than non-Indigenous
      pregnancies. Overall rates of HDP were similar for Indigenous (5.1%) and non
      Indigenous pregnancies (4.9%); however, rates were higher in normal-weight
      Indigenous pregnancies (4.0%) than in normal-weight non-Indigenous pregnancies
      (3.0%). We found that overweight or obesity was associated with higher prevalence
      of GDM, HDP, high birthweight and low Apgar score. However, the associations with
      HDP, preterm birth and low birthweight were modified by Indigenous status (P for
      interaction, < 0.001 for all). Overweight or obesity accounted for significantly
      fewer cases of HDP in Indigenous versus non-Indigenous pregnancies (population
      attributable fraction, 30% v 41%). CONCLUSIONS: Maternal overweight or obesity is
      more common among Indigenous pregnancies, and Indigenous status may modify its
      association with pregnancy outcomes. Further research needs to explore the issue
      of increased insulin resistance and higher rates of HDP among normal-weight
      Indigenous women.

PMID- 25390267
TI  - The safety of seasonal influenza vaccines in Australian children in 2013.
AB  - OBJECTIVE: To examine influenza vaccine safety in Australian children aged under
      10 years in 2013. DESIGN, PARTICIPANTS AND SETTING: Active prospective
      surveillance study conducted with parents or carers of children who received
      influenza vaccine in outpatient clinics at six tertiary paediatric hospitals or
      from selected primary health care providers between 18 March and 19 July 2013.
      MAIN OUTCOME MEASURES: Parental-reported frequency of systemic reactions (fever,
      headache, nausea, abdominal symptoms, convulsions, rash, rigors and fatigue),
      injection site reactions (erythema, swelling and/or pain at the injection site),
      use of antipyretics or analgesics, and medical attendance or advice within 72
      hours after vaccination. RESULTS: Of 981 children enrolled in the surveillance,
      893 children aged 6 months to < 10 years were eligible for inclusion. These
      children received 1052 influenza vaccine doses. Fever was reported in 5.5% (95%
      CI, 4.1%-7.3%) and 6.5% (95% CI, 3.5%-10.9%) of children after Doses 1 and 2,
      respectively. One febrile convulsion occurred in a child with a known seizure
      disorder. Injection site reactions occurred in 21.2% (95% CI, 18.5%-24.1%) and
      6.0% (95% CI, 3.1%-10.2%) after Doses 1 and 2, respectively; most were mild. Very
      few parents sought medical follow-up for their child's reaction: 22 (2.6%; 95%
      CI, 1.6%-3.9%) after Dose 1, and 11 (5.5%; 95% CI, 2.8%-9.6%) after Dose 2.
      CONCLUSIONS: These results are consistent with clinical trials and other
      observational studies of influenza vaccines currently registered for use in young
      children in Australia and can reassure parents and health care providers that
      influenza vaccination is safe and well tolerated.

PMID- 25390268
TI  - Death due to intravenous use of alpha-pyrrolidinopentiophenone.

PMID- 25390269
TI  - Measles: an important cause of fever and rash in a returned traveller.

PMID- 25390270
TI  - Collaboration between the coroner and emergency physicians: efforts to improve
      outcomes from aortic dissection.
AB  - The Coroners Prevention Unit at the Coroners Court of Victoria (CCV) is a
      multidisciplinary team that investigates deaths referred by the state's coroners,
      with a view to identifying prevention opportunities. The death of a woman from
      acute aortic dissection (AAD) after an emergency department attendance prompted
      the coroner to request a roundtable meeting with emergency physicians (EPs) from
      Melbourne. The round table was attended by 17 EPs from Melbourne hospitals, along
      with representatives from the CCV. The meeting identified important clinical,
      system and cultural features of AAD presentation and management that might be
      useful in improving case detection and management, and hence outcomes. A key
      recommendation was that EPs teach junior staff that AAD is the "subarachnoid
      haemorrhage of chest pain", to change the way patients with chest pain are
      assessed, with an emphasis on red flags for AAD being considered at the beginning
      of any discussion. This innovative collaboration between the CCV and EPs may
      serve as a model for future interactions between the CCV and the medical
      profession. 

PMID- 25390271
TI  - Medically assisted circumcision: a safer option for initiation rites.

PMID- 25390273
TI  - Let children cry.

PMID- 25390274
TI  - Robert James Furlong McInerney.

PMID- 25390275
TI  - Using "big data" to optimize public health outreach: answering the call to
      action.

PMID- 25390276
TI  - Reporting and Methodology of Multivariable Analyses in Prognostic Observational
      Studies Published in 4 Anesthesiology Journals: A Methodological Descriptive
      Review.
AB  - BACKGROUND: Prognostic research studies in anesthesiology aim to identify risk
      factors for an outcome (explanatory studies) or calculate the risk of this
      outcome on the basis of patients' risk factors (predictive studies).
      Multivariable models express the relationship between predictors and an outcome
      and are used in both explanatory and predictive studies. Model development
      demands a strict methodology and a clear reporting to assess its reliability. In
      this methodological descriptive review, we critically assessed the reporting and
      methodology of multivariable analysis used in observational prognostic studies
      published in anesthesiology journals. METHODS: A systematic search was conducted
      on Medline through Web of Knowledge, PubMed, and journal websites to identify
      observational prognostic studies with multivariable analysis published in
      Anesthesiology, Anesthesia & Analgesia, British Journal of Anaesthesia, and
      Anaesthesia in 2010 and 2011. Data were extracted by 2 independent readers.
      First, studies were analyzed with respect to reporting of outcomes, design, size,
      methods of analysis, model performance (discrimination and calibration), model
      validation, clinical usefulness, and STROBE (i.e., Strengthening the Reporting of
      Observational Studies in Epidemiology) checklist. A reporting rate was calculated
      on the basis of 21 items of the aforementioned points. Second, they were analyzed
      with respect to some predefined methodological points. RESULTS: Eighty-six
      studies were included: 87.2% were explanatory and 80.2% investigated a
      postoperative event. The reporting was fairly good, with a median reporting rate
      of 79% (75% in explanatory studies and 100% in predictive studies). Six items had
      a reporting rate <36% (i.e., the 25th percentile), with some of them not
      identified in the STROBE checklist: blinded evaluation of the outcome (11.9%),
      reason for sample size (15.1%), handling of missing data (36.0%), assessment of
      colinearity (17.4%), assessment of interactions (13.9%), and calibration (34.9%).
      When reported, a few methodological shortcomings were observed, both in
      explanatory and predictive studies, such as an insufficient number of events of
      the outcome (44.6%), exclusion of cases with missing data (93.6%), or
      categorization of continuous variables (65.1%.). CONCLUSIONS: The reporting of
      multivariable analysis was fairly good and could be further improved by checking
      reporting guidelines and EQUATOR Network website. Limiting the number of
      candidate variables, including cases with missing data, and not arbitrarily
      categorizing continuous variables should be encouraged.

PMID- 25390278
TI  - The incidence and risk factors for perioperative cardiac arrest observed in the
      national anesthesia clinical outcomes registry.
AB  - BACKGROUND: Cardiac arrest is a rare but important event in the operating room
      and postanesthesia care unit, when surgical patients are most intensively
      monitored. Several recent publications have reported the rate of cardiac arrest
      in surgical patients during the subsequent hospital stay but have not uniquely
      identified the immediate perioperative period. We hypothesized that cardiac
      arrest during this time (intraprocedure and postanesthesia care) would occur at a
      lower frequency than that described for inpatient hospital care in the available
      literature. METHODS: We extracted data from all cardiac arrests and immediate
      perioperative deaths reported to the National Anesthesia Clinical Outcomes
      Registry for the period from 2010 to 2013 and analyzed for anesthesia-related
      risk factors. We compared these data to published rates of in-hospital cardiac
      arrest after surgery. RESULTS: Overall, the risk of cardiac arrest was 5.6 per
      10,000 cases, which is less than in previous reports of in-hospital arrests in
      surgical patients overall, with an associated mortality from the arrest of 58.4%.
      The rate of cardiac arrest increased with age and ASA physical status. The rate
      of cardiac arrest was significantly higher for males, as was the mortality.
      CONCLUSIONS: The National Anesthesia Clinical Outcomes Registry is an emerging
      resource for examination of perioperative and anesthesia-related outcomes.
      Cardiac arrest is less frequent in the periprocedural setting than later in the
      hospital course, with most arrests predictably occurring in patients with ASA
      physical status III-V. The finding of increased risk of mortality in male
      patients cannot be readily explained and should prompt future research attention.

PMID- 25390277
TI  - 2-deoxy-D-glucose enhances anesthetic effects in mice.
AB  - BACKGROUND: The mechanisms of general anesthesia by volatile drugs remain largely
      unknown. Mitochondrial dysfunction and reduction in energy levels have been
      suggested to be associated with general anesthesia status. 2-Deoxy-D-glucose (2
      DG), an analog of glucose, inhibits hexokinase and reduces cellular levels of
      adenosine triphosphate (ATP). 3-Nitropropionic acid is another compound which can
      deplete ATP levels. In contrast, idebenone and L-carnitine could rescue deficits
      of energy. We therefore sought to determine whether 2-DG and/or 3-nitropropionic
      acid can enhance the anesthetic effects of isoflurane, and whether idebenone and
      L-carnitine can reverse the actions of 2-DG. METHODS: C57BL/6J mice (8 months
      old) received different concentrations of isoflurane with and without the
      treatments of 2-DG, 3-nitropropionic acid, idebenone, and L-carnitine. Isoflurane
      induced loss of righting reflex (LORR) was determined in the mice. ATP levels in
      H4 human neuroglioma cells were assessed after these treatments. Finally, 31P
      magnetic resonance spectroscopy was used to determine the effects of isoflurane
      on brain ATP levels in the mice. RESULTS: 2-DG enhanced isoflurane-induced LORR
      (P = 0.002, N = 15). 3-Nitropropionic acid also enhanced the anesthetic effects
      of isoflurane (P = 0.005, N = 15). Idebenone (idebenone + saline versus idebenone
      + 2-DG: P = 0.165, N = 15), but not L-carnitine (L-carnitine + saline versus L
      carnitine + 2-DG: P < 0.0001, N = 15), inhibited the effects of 2-DG on enhancing
      isoflurane-induced LORR in the mice, as evidenced by 2-DG not enhancing
      isoflurane-induced LORR in the mice pretreated with idebenone. Idebenone
      (idebenone + saline versus idebenone + 2-DG: P = 0.177, N = 6), but not L
      carnitine (L-carnitine + saline versus L-carnitine + 2-DG: P = 0.029, N = 6),
      also mitigated the effects of 2-DG on reducing ATP levels in cells, as evidenced
      by 2-DG not decreasing ATP levels in the cells pretreated with idebenone.
      Finally, isoflurane decreased ATP levels in both cultured cells and mouse brains
      (beta-ATP: P = 0.003, N = 10; beta-ATP/phosphocreatine: P = 0.006, N = 10; beta
      ATP/inorganic phosphate: P = 0.001, N = 10). CONCLUSIONS: These results from our
      pilot studies have established a system and generated a hypothesis that 2-DG
      enhances anesthetic effects via reducing energy levels. These findings should
      promote further studies to investigate anesthesia mechanisms.

PMID- 25390279
TI  - Propofol-induced electroencephalographic seizures in neonatal rats: the role of
      corticosteroids and gamma-aminobutyric acid type A receptor-mediated excitation.
AB  - BACKGROUND: An imbalance between excitation and inhibition in the developing
      central nervous system may result in a pathophysiological outcome. We
      investigated the mechanistic roles of endocrine activity and gamma-aminobutyric
      acid type A receptor (GABAAR)-mediated excitation in electroencephalographic
      seizures caused by the GABAAR-selective anesthetic propofol in neonatal rats.
      METHODS: Postnatal day 4-6 Sprague Dawley rats underwent a minor surgical
      procedure to implant electrodes to measure electroencephalographic activity for 1
      hour before and 1 hour after intraperitoneal administration of propofol (40
      mg.kg). Various treatments were administered 15 minutes before administration of
      propofol. RESULTS: Episodes of electroencephalographic seizures and persistent
      low-amplitude spikes occurred during propofol anesthesia. Multifold increases in
      serum levels of corticosterone (t(10) = -5.062; P = 0.0005) and aldosterone
      (t(10) = -5.069; P = 0.0005) were detected 1 hour after propofol administration
      in animals that underwent experimental manipulations identical to those used to
      study electroencephalographic activity. Pretreatment with bumetanide, the Na-K
      2Cl cotransporter inhibitor, which diminishes GABAAR-mediated excitation,
      eliminated both seizure and spike electroencephalographic activities caused by
      propofol. Mineralocorticoid and glucocorticoid receptor antagonists, RU 28318 and
      RU486, depressed electroencephalographic seizures but did not affect the spike
      electroencephalographic effects of propofol. Etomidate, at a dose sufficient to
      induce loss of righting reflex, was weak at increasing serum corticosteroid
      levels and eliciting electroencephalographic seizures. Etomidate given to
      corticosterone-pretreated rat pups further increased the total duration of
      electroencephalographic seizures caused by administration of exogenous
      corticosterone (t(21) = -2.512, P = 0.0203). CONCLUSIONS: Propofol increases
      systemic corticosteroid levels in neonatal rats, which along with GABAAR-mediated
      excitation appear to be required for propofol-induced neonatal
      electroencephalographic seizures. Enhancement of GABAAR activity alone may not be
      sufficient to elicit neonatal electroencephalographic seizures.

PMID- 25390280
TI  - Excessive postoperative bleeding and outcomes in neonates undergoing
      cardiopulmonary bypass.
AB  - BACKGROUND: Neonates undergoing cardiac surgery are especially prone to the
      hemostatic alterations of cardiopulmonary bypass (CPB) and are at high risk for
      post-CPB bleeding. An immature coagulation system, significant hemodilution from
      the CPB prime, long CPB times at low temperatures, and extensive suture lines
      increase neonates' susceptibility to bleeding after CPB. In this study, we
      examined the relationship between excessive bleeding in neonates after CPB and
      major postoperative adverse events. METHODS: We retrospectively reviewed the
      medical records of 169 neonates who underwent complex congenital heart surgery
      with CPB between January 1, 2010, and December 31, 2011. Perioperative data were
      collected and analyzed with specific focus on post-CPB bleeding as measured by 24
      hour postoperative chest tube output (CTO), post-CPB transfusion requirements,
      and major postoperative adverse events, including renal dysfunction, dialysis,
      thrombosis, extracorporeal membrane oxygenation (ECMO), and in-hospital
      mortality. We used Spearman correlation to determine correlations between
      multiple perioperative variables and 24-hour CTO and postoperative blood product
      requirements. Also, we used logistic regression analysis to determine the
      association between excessive bleeding (defined as 24-hour CTO >75th percentile)
      and major postoperative adverse events. RESULTS: Significant correlations were
      found between 24-hour CTO and postoperative blood product transfusion with
      weight, Risk Adjustment for Congenital Heart Surgery (RACHS-1) score, CPB time,
      and lowest temperature. Logistic regression found that excessive bleeding after
      CPB was an independent predictor of postoperative dialysis (relative risk [RR]
      12.0; confidence interval, 1.50-54.69; P = 0.02) and ECMO (RR 9.95; confidence
      interval, 3.07-28.47; P = 0.0008). RACHS-1 score was a significant predictor of
      in-hospital mortality (P = 0.03). CONCLUSIONS: Excessive postoperative bleeding
      in neonates after CPB is independently associated with increased adverse events,
      specifically the need for postoperative dialysis and ECMO support. Our findings
      in neonates are congruent with other recent research that also has found
      increasing transfusion requirements after pediatric CPB to be independently
      associated with an increase in major postoperative adverse events. Our results
      may aid clinicians in anticipating potential adverse events after neonatal bypass
      and in allocating the resources necessary to manage these events.

PMID- 25390281
TI  - The effectiveness of oxygen delivery and reliability of carbon dioxide waveforms:
      a crossover comparison of 4 nasal cannulae.
AB  - BACKGROUND: Effective O2 delivery and accurate end-tidal CO2 (ETCO2) sampling are
      essential features of nasal cannulae (NCs) in patients with compromised
      respiratory status. We studied 4 NC designs: bifurcated nasal prongs (NPs) with
      O2 delivery and CO2 sensing in both NPs (Hudson), separate O2/CO2 NPs (Salter),
      and CO2 sensing in NPs with cloud O2 delivery outside the NPs via multi vents
      (Oridion) and dual vents (Medline). We hypothesized that design differences
      between NCs would influence O2 delivery and ETCO2 detection. METHODS: Forty-five
      healthy volunteers, 18 to 35 years, participated in an unrestricted, randomized
      block design, each subject serving as their own control in a 4-period crossover
      study design of 4 NCs during one session. Monitoring included electrocardiogram,
      posterior pharynx O2 sampling from a Hauge Airway (Sharn Anesthesia Products,
      Tampa, FL), and NC ETCO2. In 11 volunteers, radial artery blood was sampled from
      a catheter for partial pressures of O2 and carbon dioxide (PaO2 and PaCO2)
      determination. Per randomization, each NC was positioned, and data were collected
      over 2 minutes (ETCO2, pharyngeal O2, PaO2, and PaCO2) during room air and during
      O2 fresh gas flows (FGFs) of 2, 4, and 6 Lpm. Statistical analyses were performed
      with SAS Analytics Pro, Version 9.3, and JMP Statistical Software, Version 11
      (SAS Institute Inc., Cary, NC), significance at P < 0.05. RESULTS: Blood gas
      analyses indicated PaCO2 during steady state at each experimental time period
      remained unchanged from physiologic baseline. PaO2 did not differ between NC
      devices at baseline or 2 Lpm O2. The PaO2 at 4 Lpm from the separate NPs and
      bifurcated NCs was significantly higher than the multi-vented NC. Pharyngeal O2
      with the NC with separate NPs was significantly higher than multivented and dual
      vented cloud delivery NCs at 2, 4, and 6 Lpm FGF. Pharyngeal O2 with the NC with
      bifurcated NPs was significantly higher than the multi-vented NC at 2 Lpm, and
      higher than cloud delivery NCs at 4 and 6 Lpm FGF. ETCO2 was significantly lower
      with the NC with bifurcated NPs compared to the other 3 NCs, consistent with
      errant CO2 tracings at higher FGF. CONCLUSIONS: NCs provide supplemental inspired
      O2 concentrations for patients with impaired pulmonary function. Accurate
      measures of ETCO2 are helpful in assessing respiratory rate and determining
      whether CO2 retention is occurring from hypoventilation. These findings suggest
      the NC with separate NPs was the most effective in delivering O2 and the most
      consistent at providing reliable CO2 waveforms at higher FGFs.

PMID- 25390282
TI  - The need for tacrolimus assay standardization.

PMID- 25390283
TI  - Affinity of the interface between hydroxyapatite (0001) and titanium (0001)
      surfaces: a first-principles investigation.
AB  - A basic understanding of the affinity between the hydroxyapatite (HA) and alpha
      Ti surfaces is obtained through electronic structure calculations by first
      principles method. The surface energies of HA(0001), HA (0110), HA (1011), and
      Ti(0001) surfaces have been calculated. The HA(0001) presents the most
      thermodynamically stable of HA. The HA/Ti interfaces were constructed by two
      kinds of interface models, the single interface (denoted as SI) and the double
      interface (denoted as DI). Two methods, the full relaxation and the UBER, were
      applied to determine the interfacial separation and the atomic arrangement in the
      interfacial zone. The works of adhesion of interfaces with various stoichiometric
      HA surfaces were evaluated. For the HA(0001)/Ti(0001) interfaces, the work of
      adhesion is strongly dependent on the chemical environment of the HA surface. The
      values are -2.33, -1.52, and -0.80 J/m(2) for the none-, single-, and double-Ca
      terminated HA/Ti interfaces, respectively. The influence of atomic relaxation on
      the work of adhesion and interface separation is discussed. Full relaxation
      results include -1.99 J/m(2) work of adhesion and 0.220 nm separation between HA
      and Ti for the DI of 1-Ca-HA/Ti interface, while they are -1.14 J/m(2) and 0.235
      nm by partial relaxation. Analysis of electronic structure reveals that charge
      transfer between HA and Ti slabs occurs during the formation of the HA/Ti
      interface. The transfer generates the Ti-O or Ti-Ca bonds across the interface
      and drives the HA/Ti interface system to metallic characteristic. The
      energetically favorable interfaces are formed when the outmost layer of HA
      comprises more O atoms at the interface. 

PMID- 25390284
TI  - Integrated computational and experimental protocol for understanding Rh(III)
      speciation in hydrochloric and nitric acid solutions.
AB  - Platinum group metals (PGMs), including rhodium, generated by the fission of
      (235)U are present in significant quantities within spent nuclear fuel located on
      power generation sites in the United States, the amount of which is expected to
      exceed natural reserves by 2030. Yet, spent fuel raffinates are highly acidic
      media that may result in complex speciation of the PGM. This work provides an
      understanding of Rh(III) speciation up to 9 M HCl and HNO3, and utilizes a
      combination of ultraviolet-visible (UV-vis) and capillary zone electrophoresis
      data, along with computationally predicted thermochemistry and simulated UV-vis
      spectra to approximate the relative concentrations of potential species in
      solution as a function of acid concentration. One Rh(III) species, [Rh(NO3)3], is
      observed under all conditions in HNO3 and for Rh(III) concentrations smaller than
      10(-3) M. In contrast, a variety of chloridated Rh(III) species may exist
      simultaneously in a HCl medium. The species [RhCl2(H2O)4](+) and [RhCl3(H2O)3]
      are observed in HCl solutions of concentrations ranging from 0 to 1 M; the
      species [RhCl4(H2O)2](-), [RhCl5(H2O)](2-), and [Rh2Cl9](3-) are observed between
      2 and 9 M HCl. 

PMID- 25390285
TI  - Catalyst-directed crystallographic orientation control of GaN nanowire growth.
AB  - In this work, we demonstrate that catalyst composition can be used to direct the
      crystallographic growth axis of GaN nanowires. By adjusting the ratio of gold to
      nickel in a bimetallic catalyst, we achieved selective growth of dense, uniform
      nanowire arrays along two nonpolar directions. A gold-rich catalyst resulted in
      single-crystalline nanowire growth along the ?1100? or m axis, whereas a nickel
      rich catalyst resulted in nanowire growth along the ?1120? or a axis. The same
      growth control was demonstrated on two different epitaxial substrates. Using
      proper conditions, many of the nanowires were observed to switch direction
      midgrowth, resulting in monolithic single-crystal structures with segments of two
      distinct orientations. Cathodoluminescence spectra revealed significant
      differences in the optical properties of these nanowire segments, which we
      attribute to the electronic structures of their semipolar {1122} or {1101}
      sidewalls. 

PMID- 25390286
TI  - Hepatitis C management in post-transplant patients.
AB  - Hepatitis C virus (HCV)-related cirrhosis is the leading cause for liver
      transplantation (LT) in developed countries. One of the most troubling
      complications following LT in patients with HCV is that of recurrence.
      Unfortunately, this occurs in nearly all patients with HCV. Patients suffering
      recurrence are known to have faster times to fibrosis and consequently higher
      rates of graft failure. In general, patients whom undergo transplantation for HCV
      cirrhosis have higher mortalities comparatively. It is for this reason that HCV
      in post-transplant patients must be strictly monitored for and treated. Until
      recently, treatment with standard therapy or pegylated interferon and ribavirin
      was only marginally effective and the use in this population was off-label. With
      the advent of direct acting antivirals (DAA), hopes for improved sustained
      virologic response (SVR) exists. This review will attempt to provide an update
      regarding recent data for HCV treatment in post-transplant patients, and by doing
      so, hopefully shed light on a previously dim and dreaded illness. 

PMID- 25390287
TI  - Extrahepatic manifestations of HCV.
AB  - The hepatic consequences of an infection with the hepatitis C virus (HCV) are
      well recognised, but extrahepatic manifestations of HCV may be just as severe.
      Here we have reviewed various extrahepatic manifestations of HCV such as mixed
      cryoglobulinemia, lymphoma, metabolic features and neurologic consequences and we
      discuss pathogenesis and management of these clinical problems. We concluded with
      important aspects of therapy with novel anti-HCV agents and its effects on
      extrahepatic manifestations. 

PMID- 25390288
TI  - Management of hepatitis C infection among patients with renal failure.
AB  - Hepatitis C virus (HCV) infection is a rising global public health burden with an
      estimated 130-150 million infected people worldwide and 350,000 to 500,000 HCV
      related deaths each year. Chronic kidney disease (CKD) is also a highly prevalent
      public health issue as the escalating numbers of patients worldwide are
      developing type 2 diabetes mellitus and hypertension due to high fat diets and a
      growing obesity epidemic. The high incidence and prevalence of HCV infection
      leads to substantial morbidity and mortality among renal dialysis patients.
      Recommendations are to screen for HCV infection among all patients with renal
      failure especially prior to initiation of hemodialysis and renal transplant
      evaluation. HCV-antibody enzyme immunoassay (EIA) followed by confirmation with
      HCV RNA nucleic acid test (NAT) is recommended for low prevalence regions, but in
      dialysis centers with a high prevalence of HCV, initial testing with NAT is
      recommended due to higher false positive EIA rates. Liver biopsy is used to
      assess of liver disease severity. Transjugular liver biopsy, as an effective and
      safe technique in patients with ESRD can be considered instead of percutaneous
      approach. Non-invasive approaches to staging fibrosis, including liver stiffness
      measurement by transient elastography and panels of serum fibrosis biomarkers,
      are also widely used. Although difficult to manage, combined pegylated-
      interferon (PEG IFN) and ribavirin therapy was the only treatment modality
      available for HCV-positive patients until the recently introduced new direct
      acting antiviral agents. However, except boceprevir, there are no currently
      available data to suggest that these new anti-viral drugs are safe and effective
      among end-stage renal failure patients. IFN-containing regimens were also
      associated with high rates of renal graft loss in post-renal transplant patients.
      Therefore, management of HCV infection in renal failure patients is unique and
      should be tailored individually with calculated risk/benefit ratio. New studies
      are immediately warranted to determine the safety profile and efficacy of newer
      anti-HCV drugs not only in patients with end-stage renal failure prior to kidney
      transplantation but also among kidney transplant recipients. 

PMID- 25390289
TI  - Colicky epigastric and right upper quadrant pain.

PMID- 25390290
TI  - Metal-free sigma-bond metathesis in ammonia activation by a
      diazadiphosphapentalene.
AB  - A diazadiphosphapentalene derivative 5 featuring a bent geometry with two
      phosphorus atoms at the bridgehead has been synthesized. Under mild conditions,
      compound 5 readily activated ammonia to afford 1-aza-2,3-diphospholene derivative
      6 bearing an enamine group. The reaction is therefore viewed as a formal sigma
      bond metathesis between an N-H bond of ammonia and an endocyclic P-N bond of 5.
      Details of the reaction mechanism for ammonia activation as well as subsequent
      isomerization were explored by density functional theory calculations. 

PMID- 25390291
TI  - Role of Gist and PHOG features in computer-aided diagnosis of tuberculosis
      without segmentation.
AB  - PURPOSE: Effective diagnosis of tuberculosis (TB) relies on accurate
      interpretation of radiological patterns found in a chest radiograph (CXR). Lack
      of skilled radiologists and other resources, especially in developing countries,
      hinders its efficient diagnosis. Computer-aided diagnosis (CAD) methods provide
      second opinion to the radiologists for their findings and thereby assist in
      better diagnosis of cancer and other diseases including TB. However, existing CAD
      methods for TB are based on the extraction of textural features from manually or
      semi-automatically segmented CXRs. These methods are prone to errors and cannot
      be implemented in X-ray machines for automated classification. METHODS: Gabor,
      Gist, histogram of oriented gradients (HOG), and pyramid histogram of oriented
      gradients (PHOG) features extracted from the whole image can be implemented into
      existing X-ray machines to discriminate between TB and non-TB CXRs in an
      automated manner. Localized features were extracted for the above methods using
      various parameters, such as frequency range, blocks and region of interest. The
      performance of these features was evaluated against textural features. Two
      digital CXR image datasets (8-bit DA and 14-bit DB) were used for evaluating the
      performance of these features. RESULTS: Gist (accuracy 94.2% for DA, 86.0% for
      DB) and PHOG (accuracy 92.3% for DA, 92.0% for DB) features provided better
      results for both the datasets. These features were implemented to develop a
      MATLAB toolbox, TB-Xpredict, which is freely available for academic use at
      http://sourceforge.net/projects/tbxpredict/. This toolbox provides both automated
      training and prediction modules and does not require expertise in image
      processing for operation. CONCLUSION: Since the features used in TB-Xpredict do
      not require segmentation, the toolbox can easily be implemented in X-ray
      machines. This toolbox can effectively be used for the mass screening of TB in
      high-burden areas with improved efficiency.

PMID- 25390292
TI  - Calculating electron momentum densities and Compton profiles using the linear
      tetrahedron method.
AB  - A method for computing electron momentum densities and Compton profiles from ab
      initio calculations is presented. Reciprocal space is divided into optimally
      shaped tetrahedra for interpolation, and the linear tetrahedron method is used to
      obtain the momentum density and its projections such as Compton profiles. Results
      are presented and evaluated against experimental data for Be, Cu, Ni, Fe3Pt, and
      YBa2Cu4O8, demonstrating the accuracy of our method in a wide variety of crystal
      structures. 

PMID- 25390294
TI  - Sprinters versus long-distance runners: how to grow old healthy.
AB  - So far, aging studies have concentrated on endurance athletes. Master sprint
      trained athletes were not the main focus of attention. We propose the novel
      hypothesis that the sprint model of lifelong physical training that involves high
      intensity exercise is at least as beneficial as moderate-intensity endurance
      exercise for successful aging. 

PMID- 25390293
TI  - Genomic analysis of Sleeping Beauty transposon integration in human somatic
      cells.
AB  - The Sleeping Beauty (SB) transposon is a non-viral integrating vector system with
      proven efficacy for gene transfer and functional genomics. However, integration
      efficiency is negatively affected by the length of the transposon. To optimize
      the SB transposon machinery, the inverted repeats and the transposase gene
      underwent several modifications, resulting in the generation of the hyperactive
      SB100X transposase and of the high-capacity "sandwich" (SA) transposon. In this
      study, we report a side-by-side comparison of the SA and the widely used T2
      arrangement of transposon vectors carrying increasing DNA cargoes, up to 18 kb.
      Clonal analysis of SA integrants in human epithelial cells and in immortalized
      keratinocytes demonstrates stability and integrity of the transposon
      independently from the cargo size and copy number-dependent expression of the
      cargo cassette. A genome-wide analysis of unambiguously mapped SA integrations in
      keratinocytes showed an almost random distribution, with an overrepresentation in
      repetitive elements (satellite, LINE and small RNAs) compared to a library
      representing insertions of the first-generation transposon vector and to
      gammaretroviral and lentiviral libraries. The SA transposon/SB100X integrating
      system therefore shows important features as a system for delivering large gene
      constructs for gene therapy applications. 

PMID- 25390295
TI  - Exercise for obese youth: refocusing attention from weight loss to health gains.
AB  - Despite evidence to the contrary, exercise interventions for obese youth target
      weight loss as a means of improving health. Using Exercise is Medicine(r) as a
      framework, we present a conceptual model for the beneficial effects of exercise
      independent of weight loss in obese youth and highlight novel biomarkers of
      cardiometabolic health that could prove useful as interventional targets for this
      population. 

PMID- 25390296
TI  - Intravascular ATP and the regulation of blood flow and oxygen delivery in humans.
AB  - Regulation of vascular tone is a complex response that integrates multiple
      signals that allow for blood flow and oxygen supply to match oxygen demand
      appropriately. Here, we discuss the potential role of intravascular adenosine
      triphosphate (ATP) as a primary factor in these responses and put forth the
      hypothesis that deficient ATP release contributes to impairments in vascular
      control exhibited in aged and diseased populations. 

PMID- 25390297
TI  - A framework for using GPS data in physical activity and sedentary behavior
      studies.
AB  - Global Positioning Systems (GPS) are applied increasingly in activity studies,
      yet significant theoretical and methodological challenges remain. This article
      presents a framework for integrating GPS data with other technologies to create
      dynamic representations of behaviors in context. Using more accurate and
      sensitive measures to link behavior and environmental exposures allows for new
      research questions and methods to be developed. 

PMID- 25390298
TI  - Common synaptic input to motor neurons, motor unit synchronization, and force
      control.
AB  - In considering the role of common synaptic input to motor neurons in force
      control, we hypothesize that the effective neural drive to muscle replicates the
      common input and is, thus, the main determinant of force production. Such a
      perspective argues against a significant role for motor unit synchronization in
      force control. 

PMID- 25390299
TI  - Neuromuscular exercise as treatment of degenerative knee disease.
AB  - Exercise is recommended as first-line treatment of degenerative knee disease. Our
      hypothesis is that neuromuscular exercise is feasible and at least as effective
      as traditionally used strength or aerobic training but aims to target more
      closely the sensorimotor deficiencies and functional instability associated with
      the degenerative knee disease than traditionally used training methods. 

PMID- 25390301
TI  - Debunking the myth: exercise is an effective weight loss treatment.

PMID- 25390300
TI  - The role of exercise in the rehabilitation of patients with severe burns.
AB  - Severe burn trauma results in persistent skeletal muscle catabolism and prolonged
      immobilization. We hypothesize that structured rehabilitative exercise is a safe
      and efficacious strategy to restore lean body mass and physical function in burn
      victims. Here, we review the evidence for the utility of rehabilitative exercise
      training in restoring physiological function in burn survivors. 

PMID- 25390302
TI  - Neuromuscular exercise for degenerative knees: can we optimize the treatment
      effect?

PMID- 25390304
TI  - Resting-associated vocalization emitted by captive Asian house shrews (Suncus
      murinus): acoustic structure and variability in an unusual mammalian
      vocalization.
AB  - Shrews have rich vocal repertoires that include vocalizations within the human
      audible frequency range and ultrasonic vocalizations. Here, we recorded and
      analyzed in detail the acoustic structure of a vocalization with unclear
      functional significance that was spontaneously produced by 15 adult, captive
      Asian house shrews (Suncus murinus) while they were lying motionless and resting
      in their nests. This vocalization was usually emitted repeatedly in a long series
      with regular intervals. It showed some structural variability; however, the
      shrews most frequently emitted a tonal, low-frequency vocalization with minimal
      frequency modulation and a low, non-vocal click that was clearly noticeable at
      its beginning. There was no effect of sex, but the acoustic structure of the
      analyzed vocalizations differed significantly between individual shrews. The
      encoded individuality was low, but it cannot be excluded that this individuality
      would allow discrimination of family members, i.e., a male and female with their
      young, collectively resting in a common nest. The question remains whether the
      Asian house shrews indeed perceive the presence of their mates, parents or young
      resting in a common nest via the resting-associated vocalization and whether they
      use it to discriminate among their family members. Additional studies are needed
      to explain the possible functional significance of resting-associated
      vocalizations emitted by captive Asian house shrews. Our study highlights that
      the acoustic communication of shrews is a relatively understudied topic,
      particularly considering that they are highly vocal mammals. 

PMID- 25390305
TI  - A renaissance in surgery.

PMID- 25390303
TI  - Maternally derived egg hormones, antibodies and antimicrobial proteins: common
      and different pathways of maternal effects in Japanese quail.
AB  - Avian eggs contain a variety of maternally-derived substances that can influence
      the development and performance of offspring. The levels of these egg compounds
      vary in relation to environmental and genetic factors, but little is known about
      whether there are correlative links between maternal substances in the egg
      underlying common and different pathways of maternal effects. In the present
      study, we investigated genetically determined variability and mutually adjusted
      deposition of sex hormones (testosterone-T, androstenedione-A4 and progesterone
      P4), antibodies (IgY) and antimicrobial proteins (lysozyme) in eggs of Japanese
      quail (Coturnix japonica). We used different genetic lines that were
      independently selected for yolk T concentrations, duration of tonic immobility
      and social reinstatement behaviour, since both selections for behavioural traits
      (fearfulness and social motivation, respectively) produced considerable
      correlative responses in yolk androgen levels. A higher selection potential was
      found for increased rather than decreased yolk T concentrations, suggesting that
      there is a physiological minimum in egg T levels. Line differences in yolk IgY
      concentrations were manifested within each selection experiment, but no
      consistent inter-line pattern between yolk IgY and T was revealed. On the other
      hand, a consistent inverse inter-line pattern was recorded between yolk IgY and
      P4 in both selections for behavioural traits. In addition, selections for
      contrasting fearfulness and social motivation were associated with changes in
      albumen lysozyme concentrations and an inverse inter-line pattern between the
      deposition of yolk IgY and albumen lysozyme was found in lines selected for the
      level of social motivation. Thus, our results demonstrate genetically-driven
      changes in deposition of yolk T, P4, antibodies and albumen lysozyme in the egg.
      This genetic variability can partially explain mutually adjusted maternal
      deposition of sex hormones and immune-competent molecules but the inconsistent
      pattern of inter-line differences across all selections indicates that there are
      other underlying mechanisms, which require further studies. 

PMID- 25390306
TI  - Transparency and accountability in aid: not there yet.

PMID- 25390307
TI  - London's health--going up in smoke?

PMID- 25390308
TI  - Global child health competencies for paediatricians.

PMID- 25390310
TI  - Haiti making good progress in health but challenges remain.

PMID- 25390311
TI  - Phone apps could help promote sexual health in MSM.

PMID- 25390312
TI  - Female drug users in Georgia face barriers to access therapy.

PMID- 25390313
TI  - Robotic surgery: where are we now?

PMID- 25390314
TI  - Clare Marx: new President of the Royal College of Surgeons.

PMID- 25390317
TI  - The secret scalpel: plastic surgery for wartime disguise.

PMID- 25390318
TI  - Randomised controlled trials for Ebola: practical and ethical issues.

PMID- 25390319
TI  - Antibiotic sutures against surgical site infections.

PMID- 25390320
TI  - Ebola crisis: beliefs and behaviours warrant urgent attention.

PMID- 25390321
TI  - Antibiotic sutures against surgical site infections--Authors' reply.

PMID- 25390322
TI  - Maximising the effect of combination HIV prevention in Kenya.

PMID- 25390323
TI  - Maximising the effect of combination HIV prevention in Kenya--Authors' reply.

PMID- 25390324
TI  - Syrian refugees in Turkey: effects on intensive care.

PMID- 25390325
TI  - Antifungal resistance: more research needed.

PMID- 25390326
TI  - Health-care pricing in China.

PMID- 25390328
TI  - Postinjury abdominal compartment syndrome: from recognition to prevention.
AB  - Postinjury abdominal compartment syndrome (ACS) is an example of a deadly
      clinical occurrence that was eliminated by strategic research and focused
      preventions. In the 1990s, the syndrome emerged with the widespread use of damage
      control surgery and aggressive crystalloid-based resuscitation. Patients who
      previously exsanguinated on the operating table made it to intensive care units,
      but then developed highly lethal hyperacute respiratory, renal, and cardiac
      failure due to increased abdominal pressure. Among many factors, delayed
      haemorrhage control and preload driven excessive use of crystalloid resuscitation
      were identified as modifiable predictors. The surrogate effect of preventive
      strategies, including the challenge of the 40-year-old standard of large volume
      crystalloid resuscitation for traumatic shock, greatly reduced cases of ACS. The
      discoveries were rapidly translated to civilian and military trauma surgical
      practices and fundamentally changed the way trauma patients are resuscitated
      today with substantially improved outcomes. 

PMID- 25390329
TI  - Scapular prolapse into the intrathoracic cavity in a lung transplant patient.

PMID- 25390327
TI  - The systemic immune response to trauma: an overview of pathophysiology and
      treatment.
AB  - Improvements in the control of haemorrhage after trauma have resulted in the
      survival of many people who would otherwise have died from the initial loss of
      blood. However, the danger is not over once bleeding has been arrested and blood
      pressure restored. Two-thirds of patients who die following major trauma now do
      so as a result of causes other than exsanguination. Trauma evokes a systemic
      reaction that includes an acute, non-specific, immune response associated,
      paradoxically, with reduced resistance to infection. The result is damage to
      multiple organs caused by the initial cascade of inflammation aggravated by
      subsequent sepsis to which the body has become susceptible. This Series examines
      the biological mechanisms and clinical implications of the cascade of events
      caused by large-scale trauma that leads to multiorgan failure and death, despite
      the stemming of blood loss. Furthermore, the stark and robust epidemiological
      finding--namely, that age has a profound influence on the chances of surviving
      trauma irrespective of the nature and severity of the injury--will be explored.
      Advances in our understanding of the inflammatory response to trauma, the impact
      of ageing on this response, and how this information has led to new and emerging
      treatments aimed at combating immune dysregulation and reduced immunity after
      injury will also be discussed.

PMID- 25390331
TI  - Layer-by-layer assembly of Nafion on Surlyn with ultrahigh water vapor barrier.
AB  - A layer-by-layer approach was used for the fabrication of multilayer films for
      ultra high gas barrier applications. The ultra high gas barrier material was
      designed by incorporating Nafion layer in between bilayers of poly(ethylene
      imine) and poly(acrylic acid) on a Surlyn substrate. When the barrier film with
      self-assembled Nafion is exposed to the moist environment, Nafion absorbs and
      desorbs water molecules simultaneously, thereby reducing the ingress of moisture
      in to the film. In order to study the effect of Nafion, the fabricated barrier
      materials with and without the presence of Nafion were tested for water vapor
      barrier properties. The barrier films were further used for encapsulating organic
      photovoltaic devices and were evaluated for their potential use in barrier
      applications. The devices encapsulated with the films containing Nafion exhibited
      better performance when subjected to accelerated aging conditions. Therefore,
      this study demonstrates the effectiveness of self-assembled Nafion in reducing
      the water vapor permeability by nearly five orders of magnitude and in increasing
      the lifetimes of organic devices by ~22 times under accelerated weathering
      conditions. 

PMID- 25390332
TI  - Lipopolysaccharide induces pro-inflammatory cytokines and MMP production via TLR4
      in nasal polyp-derived fibroblast and organ culture.
AB  - Nasal polyposis is characterized by persistent inflammation and remodeling in
      sinonasal mucosa. Toll-like receptors (TLRs) play a role in the innate immune
      response to microbes in the sinonasal cavity. The aim of this study was to
      evaluate whether nasal polyp-derived fibroblasts (NPDFs) and organ-cultured nasal
      polyps can synthesize pro-inflammatory cytokines and matrix metalloproteinases
      (MMPs) after exposure to lipopolysaccharide (LPS), a TLR4 agonist. NPDFs and
      organ-cultured nasal polyps were isolated from nasal polyps of 8 patients and
      exposed to LPS. The mRNA and protein expression levels of TLRs, cytokines, and
      MMPs were determined using a gene expression microarray, real-time RT-PCR,
      western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence
      staining. The enzymatic activities of MMPs were analyzed using collagen or
      gelatin zymography. The protein expression level of MMP-1 increased in nasal
      polyp tissues compared to inferior turbinate tissues. LPS induced mRNA expression
      of TLR4, IL-6, IL-8, and MMP-1 and activated MAPK signaling in NPDFs. LPS
      promoted the release of interleukin (IL)-6 through extracellular signal-related
      kinase (ERK) and IL-8 through ERK and c-Jun N-terminal kinases (JNK). Production
      of IL-6 and IL-8 was induced by PI3K/Akt signaling in LPS-stimulated NPDFs. LPS
      increased the transcript and protein expression levels of MMP-1 and induced
      collagenase activity of MMP-1 via ERK and p38, but did not induce gelatinase
      activity of MMP-2 and MMP-9. LPS from Rhodobacter sphaeroides (LPS-RS) inhibited
      the stimulatory effects of LPS in NPDFs as well as in organ culture of nasal
      polyp. LPS triggers immune response via TLR 4 and activates MAPK and PI3K/Akt
      signaling pathway, which is involved in remodeling of nasal polyps. 

PMID- 25390333
TI  - Reprogramming suppresses premature senescence phenotypes of Werner syndrome cells
      and maintains chromosomal stability over long-term culture.
AB  - Werner syndrome (WS) is a premature aging disorder characterized by chromosomal
      instability and cancer predisposition. Mutations in WRN are responsible for the
      disease and cause telomere dysfunction, resulting in accelerated aging. Recent
      studies have revealed that cells from WS patients can be successfully
      reprogrammed into induced pluripotent stem cells (iPSCs). In the present study,
      we describe the effects of long-term culture on WS iPSCs, which acquired and
      maintained infinite proliferative potential for self-renewal over 2 years. After
      long-term cultures, WS iPSCs exhibited stable undifferentiated states and
      differentiation capacity, and premature upregulation of senescence-associated
      genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency.
      WS iPSCs also showed recapitulation of the phenotypes during differentiation.
      Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of
      the descendant clones had chromosomal profiles that were similar to those of
      parental cells. These unexpected properties might be achieved by induced
      expression of endogenous telomerase gene during reprogramming, which trigger
      telomerase reactivation leading to suppression of both replicative senescence and
      telomere dysfunction in WS cells. These findings demonstrated that reprogramming
      suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to
      chromosomal stability over the long term. WS iPSCs will provide opportunities to
      identify affected lineages in WS and to develop a new strategy for the treatment
      of WS. 

PMID- 25390334
TI  - What prolongs a butterfly's life?: Trade-offs between dormancy, fecundity and
      body size.
AB  - In butterflies, life span often increases only at the expense of fecundity.
      Prolonged life span, on the other hand, provides more opportunities for
      oviposition. Here, we studied the association between life span and summer
      dormancy in two closely related species of Palearctic Meadow Brown butterflies,
      the endemic Maniola nurag and the widespread M. jurtina, from two climatic
      provenances, a Mediterranean and a Central European site, and tested the
      relationships between longevity, body size and fecundity. We experimentally
      induced summer dormancy and hence prolonged the butterflies' life in order to
      study the effects of such a prolonged life. We were able to modulate longevity
      only in Mediterranean females by rearing them under summer photoperiodic
      conditions (light 16 h : dark 8 h), thereby more than doubling their natural life
      span, to up to 246 days. Central European individuals kept their natural average
      live span under all treatments, as did Mediterranean individuals under autumn
      treatment (light 11: dark 13). Body size only had a significant effect in the
      smaller species, M. nurag, where it affected the duration of dormancy and
      lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life
      span did, surprisingly, not convey any fecundity loss. In M. nurag, which
      generally deposited fewer eggs, extended life had a fecundity cost. We conclude
      that Mediterranen M. jurtina butterflies have an extraordinary plasticity in
      aging which allows them to extend life span in response to adverse environmental
      conditions and relieve the time limitation on egg-laying while maintaining egg
      production at equal levels. 

PMID- 25390336
TI  - Tissue-specific expression of monocarboxylate transporters during fasting in
      mice.
AB  - Monocarboxylates such as pyruvate, lactate and ketone bodies are crucial for
      energy supply of all tissues, especially during energy restriction. The transport
      of monocarboxylates across the plasma membrane of cells is mediated by
      monocarboxylate transporters (MCTs). Out of 14 known mammalian MCTs, six isoforms
      have been functionally characterized to transport monocarboxylates and short
      chain fatty acids (MCT1-4), thyroid hormones (MCT8, -10) and aromatic amino acids
      (MCT10). Knowledge on the regulation of the different MCT isoforms is rare. In an
      attempt to get more insights in regulation of MCT expression upon energy
      deprivation, we carried out a comprehensive analysis of tissue specific
      expression of five MCT isoforms upon 48 h of fasting in mice. Due to the crucial
      role of peroxisome proliferator-activated receptor (PPAR)-alpha as a central
      regulator of energy metabolism and as known regulator of MCT1 expression, we
      included both wildtype (WT) and PPARalpha knockout (KO) mice in our study. Liver,
      kidney, heart, small intestine, hypothalamus, pituitary gland and thyroid gland
      of the mice were analyzed. Here we show that the expression of all examined MCT
      isoforms was markedly altered by fasting compared to feeding. Expression of MCT1,
      MCT2 and MCT10 was either increased or decreased by fasting dependent on the
      analyzed tissue. MCT4 and MCT8 were down-regulated by fasting in all examined
      tissues. However, PPARalpha appeared to have a minor impact on MCT isoform
      regulation. Due to the fundamental role of MCTs in transport of energy providing
      metabolites and hormones involved in the regulation of energy homeostasis, we
      assumed that the observed fasting-induced adaptations of MCT expression seem to
      ensure an adequate energy supply of tissues during the fasting state. Since, MCT
      isoforms 1-4 are also necessary for the cellular uptake of drugs, the fasting
      induced modifications of MCT expression have to be considered in future clinical
      care algorithms. 

PMID- 25390337
TI  - Hepatic dysfunction induced by 7, 12-dimethylbenz(alpha)anthracene and its
      obviation with erucin using enzymatic and histological changes as indicators.
AB  - The toxicity induced by 7, 12-dimethylbenz(alpha)anthracene (DMBA) has been
      widely delineated by a number of researchers. This potent chemical damages many
      internal organs including liver, by inducing the production of reactive oxygen
      species, DNA-adduct formation and affecting the activities of phase I, II,
      antioxidant and serum enzymes. Glucosinolate hydrolytic products like
      isothiocyanates (ITCs) are well known for inhibiting the DNA-adduct formation and
      modulating phase I, II enzymes. Sulforaphane is ITC, currently under phase
      trials, is readily metabolized and inter-converted into erucin upon ingestion. We
      isolated erucin from Eruca sativa (Mill.) Thell. evaluated its hepatoprotective
      role in DMBA induced toxicity in male wistar rats. The rats were subjected to
      hepatic damage by five day regular intraperitoneal doses of DMBA. At the end of
      the protocol, the rats were euthanized, their blood was collected and livers were
      processed. The liver homogenate was analyzed for phase I (NADPH-cytochrome P450
      reductase, NADH-cytochrome b5 reductase, cytochrome P450, cytochrome P420 and
      cytochrome b5), phase II (DT diaphorase, glutathione-S-transferase and gamma
      glutamyl transpeptidase) and antioxidant enzymes (superoxide dismutase, catalase,
      guaiacol peroxidise, ascorbate peroxidise, glutathione reductase and lactate
      dehydrogenase). The level of thiobarbituric acid reactive substances, lipid
      hydroperoxides, conjugated dienes and reduced glutathione in the liver homogenate
      was also analyzed. The serum was also analyzed for markers indicating hepatic
      damage (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum
      glutamic pyruvic transaminase, direct bilirubin and total bilirubin). Erucin
      provided significant protection against DMBA induced damage by modulating the
      phase I, II and antioxidant enzymes. The histological evaluation of liver tissue
      was also conducted, which showed the hepatoprotective role of erucin. 

PMID- 25390338
TI  - Structural and biophysical characterization of Bacillus thuringiensis
      insecticidal proteins Cry34Ab1 and Cry35Ab1.
AB  - Bacillus thuringiensis strains are well known for the production of insecticidal
      proteins upon sporulation and these proteins are deposited in parasporal
      crystalline inclusions. The majority of these insect-specific toxins exhibit
      three domains in the mature toxin sequence. However, other Cry toxins are
      structurally and evolutionarily unrelated to this three-domain family and little
      is known of their three dimensional structures, limiting our understanding of
      their mechanisms of action and our ability to engineer the proteins to enhance
      their function. Among the non-three domain Cry toxins, the Cry34Ab1 and Cry35Ab1
      proteins from B. thuringiensis strain PS149B1 are required to act together to
      produce toxicity to the western corn rootworm (WCR) Diabrotica virgifera
      virgifera Le Conte via a pore forming mechanism of action. Cry34Ab1 is a protein
      of ~14 kDa with features of the aegerolysin family (Pfam06355) of proteins that
      have known membrane disrupting activity, while Cry35Ab1 is a ~44 kDa member of
      the toxin_10 family (Pfam05431) that includes other insecticidal proteins such as
      the binary toxin BinA/BinB. The Cry34Ab1/Cry35Ab1 proteins represent an important
      seed trait technology having been developed as insect resistance traits in
      commercialized corn hybrids for control of WCR. The structures of Cry34Ab1 and
      Cry35Ab1 have been elucidated to 2.15 A and 1.80 A resolution, respectively. The
      solution structures of the toxins were further studied by small angle X-ray
      scattering and native electrospray ion mobility mass spectrometry. We present
      here the first published structure from the aegerolysin protein domain family and
      the structural comparisons of Cry34Ab1 and Cry35Ab1 with other pore forming
      toxins. 

PMID- 25390339
TI  - Estimated dietary intake of radionuclides and health risks for the citizens of
      Fukushima City, Tokyo, and Osaka after the 2011 nuclear accident.
AB  - The radionuclides released from the Fukushima Daiichi nuclear power plant in 2011
      pose a health risk. In this study, we estimated the 1st-year average doses
      resulting from the intake of iodine 131 (131I) and cesium 134 and 137 (134Cs and
      137Cs) in drinking water and food ingested by citizens of Fukushima City (~50 km
      from the nuclear power plant; outside the evacuation zone), Tokyo (~230 km), and
      Osaka (~580 km) after the accident. For citizens in Fukushima City, we considered
      two scenarios: Case 1, citizens consumed vegetables bought from markets; Case 2,
      citizens consumed vegetables grown locally (conservative scenario). The estimated
      effective doses of 134Cs and 137Cs agreed well with those estimated through
      market basket and food-duplicate surveys. The average thyroid equivalent doses
      due to ingestion of 131I for adults were 840 uSv (Case 1) and 2700 uSv (Case 2)
      in Fukushima City, 370 uSv in Tokyo, and 16 uSv in Osaka. The average effective
      doses due to 134Cs and 137Cs were 19, 120, 6.1, and 1.9 uSv, respectively. The
      doses estimated in this study were much lower than values reported by the World
      Health Organization and the United Nations Scientific Committee on the Effects of
      Atomic Radiation, whose assessments lacked validation and full consideration of
      regional trade in foods, highlighting the importance of including regional trade.
      The 95th percentile effective doses were 2-3 times the average values. Lifetime
      attributable risks (LARs) of thyroid cancers due to ingestion were 1.7-37*10-6
      (Case 1) and5.6-79*10-6 (Case 2) in Fukushima City, 0.73-13*10-6 in Tokyo, and
      0.04-0.49*10- 6 in Osaka. The contributions of LARs of thyroid cancers due to
      ingestion were 5.4%-11% of all exposure (Case 1) and 11%-25% (Case 2) in
      Fukushima City [corrected].

PMID- 25390341
TI  - Impact of sub-Doppler measurements on centrifugal-distortion terms: rotational
      spectrum of methyl fluoride revisited.
AB  - Methyl fluoride is a prototypical symmetric-top molecule. Despite the fact that
      its rotational spectrum has been largely investigated, centrifugal-distortion
      constants were determined only up to the sextic terms. The present investigation
      demonstrates the importance of sub-Doppler measurements in the terahertz region
      not only for deriving higher-order centrifugal-distortion terms but also for
      revising the parameters available in the literature. The Lamb-dip technique has
      been exploited for obtaining sub-Doppler resolution in the 102 GHz to 1.2 THz
      frequency range, thus allowing for the improvement of all spectroscopic
      parameters. Furthermore, the hyperfine structure due to fluorine and hydrogens
      has been resolved, thus enabling the determination of the corresponding spin
      rotation constants with an accuracy rivaling that obtained by molecular-beam
      electric resonance measurements and of the dipolar spin-spin coupling constants
      for the first time. The prediction and analysis of hyperfine structures were
      guided and supported by high-level quantum-chemical calculations of the
      parameters involved. 

PMID- 25390340
TI  - Metabolomic analysis using ultra-performance liquid chromatography-quadrupole
      time of flight mass spectrometry (UPLC-Q-TOF MS) uncovers the effects of light
      intensity and temperature under shading treatments on the metabolites in tea.
AB  - To investigate the effect of light intensity and temperature on the biosynthesis
      and accumulation of quality-related metabolites, field grown tea plants were
      shaded by Black Net and Nano-insulating Film (with additional 2-4 degrees C
      cooling effect) with un-shaded plants as a control. Young shoots were subjected
      to UPLC-Q-TOF MS followed by multivariate statistical analysis. Most flavonoid
      metabolites (mainly flavan-3-ols, flavonols and their glycosides) decreased
      significantly in the shading treatments, while the contents of chlorophyll, beta
      carotene, neoxanthin and free amino acids, caffeine, benzoic acid derivatives and
      phenylpropanoids increased. Comparison between two shading treatments indicated
      that the lower temperature under Nano shading decreased flavonols and their
      glycosides but increased accumulation of flavan-3-ols and proanthocyanidins. The
      comparison also showed a greater effect of temperature on galloylation of
      catechins than light intensity. Taken together, there might be competition for
      substrates between the up- and down-stream branches of the
      phenylpropanoid/flavonoid pathway, which was influenced by light intensity and
      temperature. 

PMID- 25390342
TI  - Standardized patient-based assessment of dermatology resident communication and
      interpersonal skills.

PMID- 25390344
TI  - Yoga for multiple sclerosis: a systematic review and meta-analysis.
AB  - While yoga seems to be effective in a number of neuropsychiatric disorders, the
      evidence of efficacy in multiple sclerosis remains unclear. The aim of this
      review was to systematically assess and meta-analyze the available data on
      efficacy and safety of yoga in patients with multiple sclerosis. Medline/PubMed,
      Scopus, the Cochrane Central Register of Controlled Trials, PsycINFO, CAM-Quest,
      CAMbase, and IndMED were searched through March 2014. Randomized controlled
      trials (RCTs) of yoga for patients with multiple sclerosis were included if they
      assessed health-related quality of life, fatigue, and/or mobility. Mood,
      cognitive function, and safety were defined as secondary outcome measures. Risk
      of bias was assessed using the Cochrane tool. Seven RCTs with a total of 670
      patients were included. Evidence for short-term effects of yoga compared to usual
      care were found for fatigue (standardized mean difference [SMD] = -0.52; 95%
      confidence intervals (CI)  =  -1.02 to -0.02; p = 0.04; heterogeneity: I2 = 60%;
      Chi2 = 7.43; p = 0.06) and mood (SMD = -0.55; 95%CI =  -0.96 to -0.13; p = 0.01;
      heterogeneity: I2 = 0%; Chi2 = 1.25; p = 0.53), but not for health-related
      quality of life, muscle function, or cognitive function. The effects on fatigue
      and mood were not robust against bias. No short-term or longer term effects of
      yoga compared to exercise were found. Yoga was not associated with serious
      adverse events. In conclusion, since no methodological sound evidence was found,
      no recommendation can be made regarding yoga as a routine intervention for
      patients with multiple sclerosis. Yoga might be considered a treatment option for
      patients who are not adherent to recommended exercise regimens.

PMID- 25390345
TI  - Synthesis of multibranched australine derivatives from reducing castanospermine
      analogues through the Amadori rearrangement of gem-diamine intermediates:
      selective inhibitors of beta-glucosidase.
AB  - A practical one-pot synthesis of bi- and triantennated australine analogues from
      a pivotal sp(2)-iminosugar-type reducing castanospermine precursor is reported.
      The transformation involves a gem-diamine intermediate that undergoes the
      indolizidine -> pyrrolizidine Amadori-type rearrangement and proceeds under
      strict control of the generalized anomeric effect to afford a single
      diastereomer. The final compounds behave as selective competitive inhibitors of
      beta-glucosidase and are promising candidates as pharmacological chaperones for
      Gaucher disease. 

PMID- 25390347
TI  - Australian fur seals (Arctocephalus pusillus doriferus) use raptorial biting and
      suction feeding when targeting prey in different foraging scenarios.
AB  - Foraging behaviours used by two female Australian fur seals (Arctocephalus
      pusillus doriferus) were documented during controlled feeding trials. During
      these trials the seals were presented with prey either free-floating in open
      water or concealed within a mobile ball or a static box feeding device. When
      targeting free-floating prey both subjects primarily used raptorial biting in
      combination with suction, which was used to draw prey to within range of the
      teeth. When targeting prey concealed within either the mobile or static feeding
      device, the seals were able to use suction to draw out prey items that could not
      be reached by biting. Suction was followed by lateral water expulsion, where
      water drawn into the mouth along with the prey item was purged via the sides of
      the mouth. Vibrissae were used to explore the surface of the feeding devices,
      especially when locating the openings in which the prey items had been hidden.
      The mobile ball device was also manipulated by pushing it with the muzzle to
      knock out concealed prey, which was not possible when using the static feeding
      device. To knock prey out of this static device one seal used targeted bubble
      blowing, where a focused stream of bubbles was blown out of the nose into the
      openings in the device. Once captured in the jaws, prey items were manipulated
      and re-oriented using further mouth movements or chews so that they could be
      swallowed head first. While most items were swallowed whole underwater, some were
      instead taken to the surface and held in the teeth, while being vigorously shaken
      to break them into smaller pieces before swallowing. The behavioural flexibility
      displayed by Australian fur seals likely assists in capturing and consuming the
      extremely wide range of prey types that are targeted in the wild, during both
      benthic and epipelagic foraging. 

PMID- 25390346
TI  - Epidermal growth factor receptor inhibition with erlotinib partially prevents
      cisplatin-induced nephrotoxicity in rats.
AB  - The effects of blocking the epidermal growth factor receptor (EGFR) in acute
      kidney injury (AKI) are controversial. Here we investigated the renoprotective
      effect of erlotinib, a selective tyrosine kinase inhibitor that can block EGFR
      activity, on cisplatin (CP)-induced AKI. Groups of animals were given either
      erlotinib or vehicle from one day before up to Day 3 following induction of CP
      nephrotoxicity (CP-N). In addition, we analyzed the effects of erlotinib on
      signaling pathways involved in CP-N by using human renal proximal tubular cells
      (HK-2). Compared to controls, rats treated with erlotinib exhibited significant
      improvement of renal function and attenuation of tubulointerstitial injury, and
      reduced the number of apoptotic and proliferating cells. Erlotinib-treated rats
      had a significant reduction of renal cortical mRNA for profibrogenic genes. The
      Bax/Bcl-2 mRNA and protein ratios were significantly reduced by erlotinib
      treatment. In vitro, we observed that erlotinib significantly reduced the
      phosphorylation of MEK1 and Akt, processes that were induced by CP in HK-2. Taken
      together, these data indicate that erlotinib has renoprotective properties that
      are likely mediated through decreases in the apoptosis and proliferation of
      tubular cells, effects that reflect inhibition of downstream signaling pathways
      of EGFR. These results suggest that erlotinib may be useful for preventing AKI in
      patients receiving CP chemotherapy.

PMID- 25390348
TI  - Biochemical indices and life traits of loggerhead turtles (Caretta caretta) from
      Cape Verde Islands.
AB  - The loggerhead turtle (Caretta caretta) is an endangered marine reptile for whom
      assessing population health requires knowledge of demographic parameters such as
      individual growth rate. In Cape Verde, as within several populations, adult
      female loggerhead sea turtles show a size-related behavioral and trophic
      dichotomy. While smaller females are associated with oceanic habitats, larger
      females tend to feed in neritic habitats, which is reflected in their
      physiological condition and in their offspring. The ratio of RNA/DNA provides a
      measure of cellular protein synthesis capacity, which varies depending on changes
      in environmental conditions such as temperature and food availability. The
      purpose of this study was to evaluate the combined use of morphometric data and
      biochemical indices as predictors of the physiological condition of the females
      of distinct sizes and hatchlings during their nesting season and how temperature
      may influence the physiological condition on the offspring. Here we employed
      biochemical indices based on nucleic acid derived indices (standardized RNA/DNA
      ratio-sRD, RNA concentration and DNA concentration) in skin tissue as a potential
      predictor of recent growth rate in nesting females and hatchling loggerhead
      turtles. Our major findings were that the physiological condition of all nesting
      females (sRD) decreased during the nesting season, but that females associated
      with neritic habitats had a higher physiological condition than females
      associated with oceanic habitats. In addition, the amount of time required for a
      hatchling to right itself was negatively correlated with its physiological
      condition (sRD) and shaded nests produced hatchlings with lower sRD. Overall, our
      results showed that nucleic acid concentrations and ratios of RNA to DNA are an
      important tool as potential biomarkers of recent growth in marine turtles. Hence,
      as biochemical indices of instantaneous growth are likely temperature-, size- and
      age-dependent, the utility and validation of these indices on marine turtles
      stocks deserves further study. 

PMID- 25390349
TI  - Cross-reactivity of EGFR mutation-specific immunohistochemistry assay in HER2
      positive tumors.
AB  - The coexpression of HER2 and EGFR L858R in a solitary nodule removed from the
      lung, whose mutation was not confirmed by molecular techniques, made us think
      about the possible existence of a cross-reaction between HER2 and the EGFR L858R
      specific antibody. Our study was designed to further analyze the existence of
      this cross-reaction and stress the need to exclude a metastatic breast cancer
      when dealing with EGFR L858R-positive cases. The series consists of 42 primary
      breast carcinomas, 22 HER2 positive for overexpression and amplification, and 20
      negative for both. EGFR mutations were studied by immunohistochemistry and
      confirmed using real-time PCR when positive. Immunohistochemistry assay with EGFR
      L858R was positive in 19 (86%) of the HER2-positive breast carcinomas and
      negative in all HER2-negative carcinomas. The EGFR L858R antibody gives false
      positive results in most of the breast carcinomas with HER2
      overexpression/amplification. As a consequence, it is essential to confirm any
      EGFR L858R-positive cases by molecular methods or at least discard the presence
      of HER2 overexpression/amplification before rendering a diagnosis. It is also
      important to consider that HER2 has been described in other carcinomas such as
      urothelial, gastric or ovarian, as well as lung, although infrequently. 

PMID- 25390350
TI  - Immunohistochemical expression of TGF-beta1 in lichen planus.
AB  - BACKGROUND: Lichen planus (LP) is a chronic recurrent rash of unknown cause with
      no established cure. Clinical and immunohistochemical studies strongly support an
      immunologic basis for the disease. There has been growing evidence suggesting a
      role for transforming growth factor beta1 (TGF-beta1) in the pathogenesis of LP.
      OBJECTIVE: The aim of the present study was to investigate the possible role of
      TGF-beta1 in the pathogenesis of LP. MATERIALS AND METHODS: TGF-beta1 was
      analyzed on skin biopsies of 25 patients presenting with LP and 10 age-matched
      and sex-matched normal subjects (controls). RESULTS: TGF-beta1 was expressed in
      keratinocytes of 70% of the control group and 48% of LP cases with a significant
      difference in intensities of expression (P=0.01). In LP, moderate intensity of
      keratinocyte expression was significantly associated with frequent apoptosis
      (P=0.04). Dermal lymphocytes showed positive expression in 80% and intense
      expression was significantly associated with absent hyperkeratosis (P=0.03). Only
      2 cases showed mild expression in epidermal lymphocytes. CONCLUSIONS: Reduced TGF
      beta1 expression in LP may participate in immune dysregulation of the disease.

PMID- 25390352
TI  - Different expressions of large-conductance Ca2+-activated K+ channels in the
      mouse renal cortex and hippocampus during postnatal development.
AB  - Large-conductance Ca(+)-activated K(+) (BKCa) channels are widely distributed in
      a variety of cells and play a pivotal and specific role in many
      pathophysiological conditions. However, the function of BK(Ca) channels in the
      kidney cortex and hippocampus during the postnatal development has not received
      attention. In this study, to elucidate the role of BK(Ca) channels during the
      development, it is essential to establish the location and quantitation of
      expression of BK(Ca). The expressions of BK(Ca) were detected in the kidney and
      hippocampus on postnatal days (P) 1, 3, 5, 7, 14, 21, 28, and 49 by
      immunohistochemical and Western blot analysis. Our results showed that
      expressions of BK(Ca) channels were found in tubules and corpuscles at all time
      points. The expression was also observed at all developmental stages of the renal
      corpuscles, such as comma-shaped body, S-shaped body, renal corpuscles of stage
      III, and renal corpuscles of stage IV. During the development, the expression of
      BK(Ca) channels was decreased and the most prominent change of BK(Ca) protein
      level appeared between P14 and P21. In contrast, BK(Ca) channels were expressed
      in all regions of the hippocampus at every time point with the level increasing
      during the early development (P1 to P14). The findings of the present study
      suggest that BKCa channels play an important role during the postnatal
      development in both the renal cortex and hippocampus.

PMID- 25390351
TI  - Expression of the chemokine receptor gene, CCR8, is associated With DUSP22
      rearrangements in anaplastic large cell lymphoma.
AB  - Anaplastic large cell lymphoma (ALCL) is one of the most common T-cell non
      Hodgkin lymphomas and has 2 main subtypes: an anaplastic lymphoma kinase (ALK)
      positive subtype characterized by ALK gene rearrangements and an ALK-negative
      subtype that is poorly understood. We recently identified recurrent
      rearrangements of the DUSP22 locus on 6p25.3 in both primary cutaneous and
      systemic ALK-negative ALCLs. This study aimed to determine the relationship
      between these rearrangements and expression of the chemokine receptor gene, CCR8.
      CCR8 has skin-homing properties and has been suggested to play a role in limiting
      extracutaneous spread of primary cutaneous ALCLs. However, overexpression of CCR8
      has also been reported in systemic ALK-negative ALCLs. As available antibodies
      for CCR8 have shown lack of specificity, we examined CCR8 expression using
      quantitative real-time PCR in frozen tissue and RNA in situ hybridization (ISH)
      in paraffin tissue. Both approaches showed higher CCR8 expression in ALCLs with
      DUSP22 rearrangements than in nonrearranged cases (PCR: 19.5-fold increase,
      P=0.01; ISH: 3.3-fold increase, P=0.0008). CCR8 expression was not associated
      with cutaneous presentation, cutaneous biopsy site, or cutaneous involvement
      during the disease course. These findings suggest that CCR8 expression in ALCL is
      more closely related to the presence of DUSP22 rearrangements than to cutaneous
      involvement and that the function of CCR8 may extend beyond its skin-homing
      properties in this disease. This study also underscores the utility of RNA-ISH as
      a paraffin-based method for investigating gene expression when reliable
      antibodies for immunohistochemical analysis are not available. 

PMID- 25390353
TI  - Matrix Metalloproteinase-9 Expression in Calcified Human Aortic Valves: A
      Histopathologic, Immunohistochemical, and Ultrastructural Study.
AB  - The hallmarks of calcific aortic valve disease (CAVD) are the significant
      quantitative and qualitative changes that occur in the extracellular matrix
      (ECM), which ultimately lead to increased leaflet stiffness and obstruction of
      left ventricular outflow. Mounting evidence suggests that ECM remodeling not only
      contribute to valve cell dysfunction but also alter certain cell signaling
      pathways responsible for the initiation and progression of the disease state.
      Matrix metalloproteinases (MMPs), collectively called matrixins, are a family of
      enzymes known to participate in numerous ECM remodeling events during embryonic
      development and in disease. The aim of the present study was to evaluate whether
      changes in MMP-9 expression might be involved in the pathophysiology of CAVD. For
      this purpose, we have analyzed a total of 19 pathologic valves from patients who
      underwent aortic valve replacement for calcific aortic stenosis. Microscopically,
      the cusp tissue showed diffuse fibrosis, neovascularization, and abnormal ECM
      remodeling with collagen disorganization and mineralization. Western blot and
      immunohistochemical analyses have been performed on both the areas overlying and
      remote from the mineral deposits. Protein expression data evidenced a significant
      upregulation of MMP-9 in the calcified lesion area. Consistent with these
      observations, immunohistochemistry demonstrated that MMP-9 protein was almost
      exclusively localized near or around the mineralized nodules, whereas was
      generally quite weak or absent in areas devoid of any calcification. Our data
      suggest that MMP-9 may play a key role in CAVD probably by promoting the fibrotic
      and procalcific remodeling of the ECM. 

PMID- 25390354
TI  - High-quality RNA extracted from biopsied samples dehydrated and stored dried at
      room temperature without chemical preservation for up to 3 months as evidenced by
      RT-PCR results.
AB  - Handling and maintenance of biological tissues for nucleic acid and/or protein
      analysis has long been a challenge because of the perceived instability of these
      molecules at room temperature if not preserved or processed. Structural damage
      and compromised integrity of aforementioned biomolecules subsequent to
      preservation have also posed difficulties in their use in research. The
      development of technologies employing nonfixative methods with the capability to
      store at room temperature have been of growing interest. Our previous publication
      exploring preservation of proteins by desiccation challenged the convention of
      their unstable nature. Herein, we report the results of quantitative and
      qualitative analyses of RNA from tissue samples that were desiccated and stored
      at room temperature for up to 3 months. Our results indicate that viable RNA can
      be obtained from dehydrated ex vivo tissue samples that have been stored at room
      temperature. 

PMID- 25390355
TI  - Allantoic, vitelline, and "hybrid" embryonic vestiges of the umbilical cord: an
      immunohistochemical study.
AB  - The embryonic origin of umbilical cord vestiges is well documented; however,
      their immunophenotype is unknown. This study was conducted to determine whether
      vitelline and allantoic remnants can be differentiated using immunohistochemical
      markers. All allantoic remnants were stained with p63 and were negative for CDX2,
      whereas the vitelline remnants stained with CDX2 and were negative for p63. An
      unexpected finding was a small number of morphologically ambiguous cases that
      stained with both markers in a complimentary manner. The term "hybrid" remnant is
      proposed for these remnants. 

PMID- 25390356
TI  - A Case in Point: When Extended Genotyping of alpha-1 Antitrypsin (SERPINA1) is
      Indicated.

PMID- 25390357
TI  - Phenotype and immunophenotype of the most common pediatric tumors.
AB  - Pediatric tumors are heterogenous and can be quite varied in appearance. However,
      those in the infamous "small round blue-cell tumor" group, with their
      hyperchromatic nuclei and small amount of cytoplasm can be challenging, and their
      diagnosis and prognostication require cost-efficient and focused
      immunohistochemistry and ancillary testing. Ideally, ample material should be
      obtained for routine histology and ancillary testing, including
      immunohistochemistry, fluorescent in situ hybridization, fresh tissue for
      cytogenetic studies, and snap-frozen tumor for DNA/RNA extraction both for
      routine molecular testing (ie, reverse-transcription PCR studies), as well as
      future research study protocols (genome wide studies, targeted gene sequencing).
      This review focuses on the main pediatric tumors with emphasis on
      immunophenotype, keeping in mind that a directed panel approach yields the
      highest yield with combination of clinical history, histologic features, and
      ancillary molecular testing.

PMID- 25390358
TI  - Phenotype-genotype correlation in Wilson disease in a large Lebanese family:
      association of c.2299insC with hepatic and of p. Ala1003Thr with neurologic
      phenotype.
AB  - Genotype phenotype correlations in Wilson disease (WD) are best established in
      homozygous patients or in compound heterozygous patients carrying the same set of
      mutations. We determined the clinical phenotype of patients with WD carrying the
      c.2298_2299insC in Exon 8 (c.2299insC) or the p. Ala1003Thr missense substitution
      in Exon 13 mutations in the homozygous or compound heterozygous state. We
      investigated 76 members of a single large Lebanese family. Their genotypes were
      determined, and clinical assessments were carried out for affected subjects. We
      also performed a literature search retrieving the phenotypes of patients carrying
      the same mutations of our patients in the homozygous or compound heterozygous
      state. There were 7 consanguineous marriages in this family and the prevalence of
      WD was 8.9% and of carriers of ATP7B mutation 44.7%. WD was confirmed in 9 out of
      76 subjects. All 9 had the c.2299insC mutation, 5 homozygous and 4-compound
      heterozygous with p. Ala1003Thr. Six of our patients had hepatic, 2 had
      neurologic and 1 had asymptomatic phenotype. Based on our data and a literature
      review, clear phenotypes were reported for 38 patients worldwide carrying the
      c.2299insC mutation. About 53% of those have hepatic and 29% have neurologic
      phenotype. Furthermore, there were 10 compound heterozygous patients carrying the
      p. Ala1003Thr mutation. Among those, 80% having c.2299insC as the second mutation
      had hepatic phenotype, and all others had neurologic phenotype. We hereby report
      an association between the c.2299insC mutation and hepatic phenotype and between
      the p. Ala1003Thr mutation and neurologic phenotype. 

PMID- 25390359
TI  - Impact of protein domains on PE_PGRS30 polar localization in Mycobacteria.
AB  - PE_PGRS proteins are unique to the Mycobacterium tuberculosis complex and a
      number of other pathogenic mycobacteria. PE_PGRS30, which is required for the
      full virulence of M. tuberculosis (Mtb), has three main domains, i.e. an N
      terminal PE domain, repetitive PGRS domain and the unique C-terminal domain. To
      investigate the role of these domains, we expressed a GFP-tagged PE_PGRS30
      protein and a series of its functional deletion mutants in different
      mycobacterial species (Mtb, Mycobacterium bovis BCG and Mycobacterium smegmatis)
      and analysed protein localization by confocal microscopy. We show that PE_PGRS30
      localizes at the mycobacterial cell poles in Mtb and M. bovis BCG but not in M.
      smegmatis and that the PGRS domain of the protein strongly contributes to protein
      cellular localization in Mtb. Immunofluorescence studies further showed that the
      unique C-terminal domain of PE_PGRS30 is not available on the surface, except
      when the PGRS domain is missing. Immunoblot demonstrated that the PGRS domain is
      required to maintain the protein strongly associated with the non-soluble
      cellular fraction. These results suggest that the repetitive GGA-GGN repeats of
      the PGRS domain contain specific sequences that contribute to protein cellular
      localization and that polar localization might be a key step in the PE_PGRS30
      dependent virulence mechanism. 

PMID- 25390360
TI  - Multifunctional PEG retinylamine conjugate provides prolonged protection against
      retinal degeneration in mice.
AB  - A polyethylene glycol (PEG) retinylamine (Ret-NH2) conjugate PEG-GFL-NH-Ret with
      a glycine-phenylalanine-leucine (GFL) spacer was synthesized for controlled oral
      delivery of Ret-NH2 to treat retinal degenerative diseases, including Stargardt
      disease (STGD) and age-related macular degeneration (AMD). The peptide spacer was
      introduced for sustained release of the drug by digestive enzymes in the
      gastrointestinal tract. The pharmacokinetics experiments showed that the PEG
      conjugate could control the sustained drug release after oral administration and
      had much lower nonspecific liver drug accumulation than the free drug in wild
      type female C57BL mice. In the mean time, the conjugate maintained the same
      concentration of Ret-NH2 in the eye as the free drug. Also, PEG-GFL-NH-Ret at a
      Ret-NH2 equivalent dose of 25 mg/kg produced complete protection of Abca4(-/
      )Rdh8(-/-) mouse retinas against light-induced retinal degeneration for 3 days
      after oral administration, as revealed by OCT retina imaging, whereas free Ret
      NH2 did not provide any protection under identical conditions. The polymer
      conjugate PEG-GFL-NH-Ret has great potential for controlled delivery of Ret-NH2
      to the eye for effective protection against retinal degenerative diseases.

PMID- 25390362
TI  - In singulo probing of viral RNA dynamics by multichromophore fluorescence
      dequenching.
AB  - Current understanding of virus life-cycle states and transitions between them is
      mainly built on knowledge of the protein shell structure encapsulating the
      genome. Little is known about the genome fate during viral transitions. Here,
      changes in the fluorescence rate from multilabeled transcript viral RNAs
      encapsulated in Brome mosaic virus capsids were examined as a function of the RNA
      state. A simple kinetic model relating chain compactness to single-molecule
      fluorescence emission suggests that in a dense multichromophore system the rate
      of energy transfer should scale with distance more gradually than the rate of the
      Forster energy transfer between two chromophores, which varies sharply as the
      reciprocal of distance to the sixth power. As a proof-of-principle experiment, we
      have compared predictions from a numerical model for confined diffusive motion
      with the fluorescence emission from virus-encapsulated and free single RNA
      molecules decorated with multiple cyanine dyes and encapsulated inside
      microscopic emulsion droplets. We found that the effective quantum yield per
      labeled particle depends on the expansion state, in agreement with theoretical
      predictions. Since fluorescence single particle tracking is now a well
      established methodology for the study of virus life cycle, the findings reported
      here may pave the way toward reducing the existing gap between in vitro and
      cellular in singulo studies of the fates of viral RNA. 

PMID- 25390361
TI  - A FTIR imaging characterization of fibroblasts stimulated by various breast
      cancer cell lines.
AB  - It is well known that the microenvironment plays a major role in breast cancer
      progression. Yet, the mechanism explaining the transition from normal fibroblasts
      to cancer-stimulated fibroblasts remains to be elucidated. Here we report a FTIR
      imaging study of the effects of three different breast cancer cell lines on
      normal fibroblasts in culture. Fibroblast activation process was monitored by
      FTIR imaging and spectra compared by multivariate statistical analyses. Principal
      component analysis evidenced that the fibroblasts stimulated by these cancer cell
      lines grouped together and remained distinctly separated from normal fibroblasts
      indicating a modified different chemical composition in the cancer-stimulated
      fibroblasts. Similar changes in fibroblasts were induced by the various breast
      cancer cell lines belonging to different sub-types. Most significant changes were
      observed in the region of 2950 and 1230 cm(-1), possibly related to changes in
      lipids and in the 1230 cm(-1) area assigned to phosphate vibrations
      (nucleotides). Interestingly, the cancer-cell induced changes in the fibroblasts
      also occurred when there was no possible direct contact between the two cell
      lines in the co-culture. When contact was possible, the spectral changes were
      similar, suggesting that soluble factors but not direct cell-cell interactions
      were responsible for fibroblast activation. Overall, the results indicate that IR
      imaging could be used in the future for analyzing the microenvironment of breast
      tumors.

PMID- 25390364
TI  - The influence of experimental parameters and specimen geometry on the mass
      spectra of copper during pulsed-laser atom-probe tomography.
AB  - We have studied the influence of experimental factors and specimen geometry on
      the quality of the mass spectra in copper (Cu) during pulsed-laser atom-probe
      tomography. We have evaluated the effects of laser pulse energy, laser pulse
      frequency, specimen base temperature, specimen tip radius, and specimen tip shank
      half-angle on the effects of mass resolving power, (m/Deltam), at full-width at
      half-maximum and at full-width at tenth-maximum, the tail size after the major
      mass-to-charge state (m/n) ratio peaks, and the mass spectra. Our results
      indicate that mass resolving power improves with decreasing pulse energy between
      40 and 80 pJ and decreasing base temperature between 20 and 80 K. The mass
      resolving power also improves with increasing tip radius and shank half-angle. A
      pulse frequency of 250 kHz slightly improves the mass resolving power relative to
      100 or 500 kHz. The tail size decreases with increasing pulse energy. The mass
      resolving power improves when the cooling time is reduced, which is influenced by
      the thermal diffusivity of Cu and the specimen base temperature. 

PMID- 25390365
TI  - Adaptive robotic control driven by a versatile spiking cerebellar network.
AB  - The cerebellum is involved in a large number of different neural processes,
      especially in associative learning and in fine motor control. To develop a
      comprehensive theory of sensorimotor learning and control, it is crucial to
      determine the neural basis of coding and plasticity embedded into the cerebellar
      neural circuit and how they are translated into behavioral outcomes in learning
      paradigms. Learning has to be inferred from the interaction of an embodied system
      with its real environment, and the same cerebellar principles derived from cell
      physiology have to be able to drive a variety of tasks of different nature,
      calling for complex timing and movement patterns. We have coupled a realistic
      cerebellar spiking neural network (SNN) with a real robot and challenged it in
      multiple diverse sensorimotor tasks. Encoding and decoding strategies based on
      neuronal firing rates were applied. Adaptive motor control protocols with
      acquisition and extinction phases have been designed and tested, including an
      associative Pavlovian task (Eye blinking classical conditioning), a vestibulo
      ocular task and a perturbed arm reaching task operating in closed-loop. The SNN
      processed in real-time mossy fiber inputs as arbitrary contextual signals,
      irrespective of whether they conveyed a tone, a vestibular stimulus or the
      position of a limb. A bidirectional long-term plasticity rule implemented at
      parallel fibers-Purkinje cell synapses modulated the output activity in the deep
      cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain
      of the motor responses by tuning its output discharge. It succeeded in
      reproducing how human biological systems acquire, extinguish and express
      knowledge of a noisy and changing world. By varying stimuli and perturbations
      patterns, real-time control robustness and generalizability were validated. The
      implicit spiking dynamics of the cerebellar model fulfill timing, prediction and
      learning functions. 

PMID- 25390366
TI  - Patterns of stove usage after introduction of an advanced cookstove: the long
      term application of household sensors.
AB  - Household air pollution generated from solid fuel use for cooking is one of the
      leading risk factors for ill-health globally. Deployment of advanced cookstoves
      to reduce emissions has been a major focus of intervention efforts. However,
      household usage of these stoves and resulting changes in usage of traditional
      polluting stoves is not well characterized. In Palwal District, Haryana, India,
      we carried out an intervention utilizing the Philips HD4012 fan-assisted stove,
      one of the cleanest biomass stoves available. We placed small, unobtrusive data
      logging iButton thermometers on both the traditional and Philips stoves to
      collect continuous data on use patterns in 200 homes over 60 weeks. Intervention
      stove usage declined steadily over time and stabilized after approximately 200
      days; use of the traditional stove remained relatively constant. We additionally
      evaluated how well short-duration usage measures predicted long-term use.
      Measuring usage over time of both traditional and intervention stoves provides
      better understanding of cooking behaviors and can lead to more precise
      quantification of potential exposure reductions and consequent health benefits
      attributable to interventions. 

PMID- 25390367
TI  - Implementation of a smart pump champions program to decrease potential patient
      harm.
AB  - Compliance with safety features on smart pumps with drug libraries is a challenge
      for health care systems. Noncompliance and workarounds heighten the risk for
      adverse drug events and subsequent costs of patient care. This quality
      improvement project describes a pump champion innovation implemented over a 6
      month period. There was a significant increase in nurses' compliance to drug
      library software in smart pumps and a decrease in severe harms averted. 

PMID- 25390369
TI  - MM-MDS: a multidimensional scaling database with similarity ratings for 240
      object categories from the Massive Memory picture database.
AB  - Cognitive theories in visual attention and perception, categorization, and memory
      often critically rely on concepts of similarity among objects, and empirically
      require measures of "sameness" among their stimuli. For instance, a researcher
      may require similarity estimates among multiple exemplars of a target category in
      visual search, or targets and lures in recognition memory. Quantifying
      similarity, however, is challenging when everyday items are the desired stimulus
      set, particularly when researchers require several different pictures from the
      same category. In this article, we document a new multidimensional scaling
      database with similarity ratings for 240 categories, each containing color
      photographs of 16-17 exemplar objects. We collected similarity ratings using the
      spatial arrangement method. Reports include: the multidimensional scaling
      solutions for each category, up to five dimensions, stress and fit measures,
      coordinate locations for each stimulus, and two new classifications. For each
      picture, we categorized the item's prototypicality, indexed by its proximity to
      other items in the space. We also classified pairs of images along a continuum of
      similarity, by assessing the overall arrangement of each MDS space. These
      similarity ratings will be useful to any researcher that wishes to control the
      similarity of experimental stimuli according to an objective quantification of
      "sameness." 

PMID- 25390368
TI  - Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42
      oligomer binding to specific neuronal receptors is displaced by drug candidates
      that improve cognitive deficits.
AB  - Synaptic dysfunction and loss caused by age-dependent accumulation of
      synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie
      cognitive decline in Alzheimer's disease (AD). Alterations in membrane
      trafficking induced by Abeta oligomers mediates reduction in neuronal surface
      receptor expression that is the basis for inhibition of electrophysiological
      measures of synaptic plasticity and thus learning and memory. We have utilized
      phenotypic screens in mature, in vitro cultures of rat brain cells to identify
      small molecules which block or prevent the binding and effects of Abeta
      oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal
      synapses and induce deficits in membrane trafficking in neuronal cultures with an
      EC50 that corresponds to its binding affinity. The therapeutic lead compounds we
      have found are pharmacological antagonists of Abeta oligomers, reducing the
      binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons
      and preventing and treating oligomer-induced deficits in membrane trafficking.
      These molecules are highly brain penetrant and prevent and restore cognitive
      deficits in mouse models of Alzheimer's disease. Counter-screening these
      compounds against a broad panel of potential CNS targets revealed they are highly
      potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations
      of the compounds corresponding to greater than 80% receptor occupancy at the
      sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn
      mice. These studies demonstrate that synthetic and human-derived Abeta oligomers
      act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit
      saturable binding to a target, they exert a functional effect related to their
      binding and their displacement by small molecule antagonists blocks their
      functional effect. The first-in-class small molecule receptor antagonists
      described here restore memory to normal in multiple AD models and sustain
      improvement long-term, representing a novel mechanism of action for disease
      modifying Alzheimer's therapeutics.

PMID- 25390370
TI  - Diagnostic criteria for depression in type 2 diabetes: a data-driven approach.
AB  - BACKGROUND: While depression is a frequent psychiatric comorbid condition in
      diabetes and has significant clinical impact, the syndromal profile of depression
      and anxiety symptoms has not been examined in detail. AIMS: To determine the
      syndromal pattern of the depression and anxiety spectrum in a large series of
      patients with type 2 diabetes, as determined using a data-driven approach based
      on latent class analysis (LCA). METHOD: Type 2 diabetes participants from the
      observational community-based Fremantle Diabetes Study Phase II underwent
      assessment of lifetime depression using the Brief Lifetime Depression Scale, the
      Patient Health Questionnaire 9-item version (PHQ-9) for current depression
      symptoms, and the Generalized Anxiety Disorder Scale that was specifically
      developed and validated for this study. The main outcome measure was classes of
      patients with a specific syndromal profile of depression and anxiety symptoms
      based on LCA. RESULTS: LCA identified four classes that were interpreted as
      "major anxious depression", "minor anxious depression", "subclinical anxiety",
      and "no anxious depression". All nine DSM-IV/5 diagnostic criteria for major
      depression identified a class with a high frequency of major depression. All
      symptoms of anxiety had similar high probabilities as symptoms of depression for
      the "major depression-anxiety" class. There were significant differences between
      classes in terms of history of depression and anxiety, use of psychoactive
      medication, and diabetes-related variables. CONCLUSIONS: Patients with type 2
      diabetes show specific profiles of depression and anxiety. Anxiety symptoms are
      an integral part of major depression in type 2 diabetes. The different classes
      identified here provide empirically validated phenotypes for future research.

PMID- 25390373
TI  - Bilateral vascular occlusions of the anterior visual pathway and cocaine abuse.
AB  - PURPOSE: Describe bilateral vision loss from ischemic injury of the anterior
      visual pathway due to recreational cocaine. METHODS: Case report. PATIENT: A 33
      year-old man presented to the emergency room with headache associated with
      multiple cerebral hemispheric lesions on computed tomogram. RESULTS: During
      hospital admission, he lost vision from a right central retinal artery occlusion
      and an ischemic event to the left optic nerve head. Extensive diagnostic
      evaluation was unrewarding. The patient admitted to persistent cocaine abuse
      after his 2-month hospitalization. CONCLUSION: The diagnosis of cocaine-related
      vascular occlusion to the anterior visual pathway may not be considered because
      physicians are unaware of these ocular side effects.

PMID- 25390371
TI  - Evolution of an expanded mannose receptor gene family.
AB  - Sequences of peptides from a protein specifically immunoprecipitated by an
      antibody, KUL01, that recognises chicken macrophages, identified a homologue of
      the mammalian mannose receptor, MRC1, which we called MRC1L-B. Inspection of the
      genomic environment of the chicken gene revealed an array of five paralogous
      genes, MRC1L-A to MRC1L-E, located between conserved flanking genes found either
      side of the single MRC1 gene in mammals. Transcripts of all five genes were
      detected in RNA from a macrophage cell line and other RNAs, whose sequences
      allowed the precise definition of spliced exons, confirming or correcting
      existing bioinformatic annotation. The confirmed gene structures were used to
      locate orthologues of all five genes in the genomes of two other avian species
      and of the painted turtle, all with intact coding sequences. The lizard genome
      had only three genes, one orthologue of MRC1L-A and two orthologues of the MRC1L
      B antigen gene resulting from a recent duplication. The Xenopus genome, like that
      of most mammals, had only a single MRC1-like gene at the corresponding locus.
      MRC1L-A and MRC1L-B genes had similar cytoplasmic regions that may be indicative
      of similar subcellular migration and functions. Cytoplasmic regions of the other
      three genes were very divergent, possibly indicating the evolution of a new
      functional repertoire for this family of molecules, which might include novel
      interactions with pathogens. 

PMID- 25390372
TI  - A supplementary system for a brain-machine interface based on jaw artifacts for
      the bidimensional control of a robotic arm.
AB  - Non-invasive Brain-Machine Interfaces (BMIs) are being used more and more these
      days to design systems focused on helping people with motor disabilities.
      Spontaneous BMIs translate user's brain signals into commands to control devices.
      On these systems, by and large, 2 different mental tasks can be detected with
      enough accuracy. However, a large training time is required and the system needs
      to be adjusted on each session. This paper presents a supplementary system that
      employs BMI sensors, allowing the use of 2 systems (the BMI system and the
      supplementary system) with the same data acquisition device. This supplementary
      system is designed to control a robotic arm in two dimensions using
      electromyographical (EMG) signals extracted from the electroencephalographical
      (EEG) recordings. These signals are voluntarily produced by users clenching their
      jaws. EEG signals (with EMG contributions) were registered and analyzed to obtain
      the electrodes and the range of frequencies which provide the best classification
      results for 5 different clenching tasks. A training stage, based on the 2
      dimensional control of a cursor, was designed and used by the volunteers to get
      used to this control. Afterwards, the control was extrapolated to a robotic arm
      in a 2-dimensional workspace. Although the training performed by volunteers
      requires 70 minutes, the final results suggest that in a shorter period of time
      (45 min), users should be able to control the robotic arm in 2 dimensions with
      their jaws. The designed system is compared with a similar 2-dimensional system
      based on spontaneous BMIs, and our system shows faster and more accurate
      performance. This is due to the nature of the control signals. Brain potentials
      are much more difficult to control than the electromyographical signals produced
      by jaw clenches. Additionally, the presented system also shows an improvement in
      the results compared with an electrooculographic system in a similar environment.

PMID- 25390374
TI  - Combined cilioretinal artery and partial central retinal vein occlusion in the
      postpartum period.
AB  - PURPOSE: To report a combined cilioretinal artery and partial central retinal
      vein occlusion shortly after delivery in a twin-pregnant woman. METHODS: A 25
      year-old woman presented to our clinic with the complaint of blurred vision in
      the right eye 1 week after delivery. She underwent detailed ophthalmic and
      systemic investigations. RESULTS: The patient had an uncomplicated twin
      pregnancy. Ocular examination showed combined cilioretinal artery and partial
      central retinal vein occlusion in the right eye. Systemic diseases were excluded.
      Laboratory evaluations revealed increased plasma d-dimer level (1.64 mg/mL).
      Spontaneous recovery occurred without treatment 1 month after delivery.
      CONCLUSION: Twin pregnancy may lead to exaggerated hypercoagulability and
      increased d-dimer level in pregnant women. This situation may be a risk factor
      for retinochoroidal vascular occlusions.

PMID- 25390375
TI  - Bilateral retinal branch vascular occlusion-a first presentation of crohn
      disease.
AB  - PURPOSE: To describe a case of Crohn disease presenting as a branch retinal
      artery occlusion in one eye and branch retinal vein occlusion in the other eye as
      a first presentation. METHODS: Case report. RESULTS: A 34-year-old man presented
      with simultaneous left superotemporal branch retinal artery and right
      superotemporal branch retinal vein vasculitic occlusion in the absence of other
      signs of intraocular inflammation. Extensive investigations over 6 months
      directed primarily at vasculitides, coagulopathies, and atypical infections
      failed to reveal the underlying diagnosis. A subsequent presentation with
      gastrointestinal manifestations led to a colonic biopsy and the diagnosis of
      Crohn disease. A combination of azathioprine and low-dose steroids was effective
      in the maintenance of remission of this disorder. CONCLUSION: Inflammatory bowel
      disease should be considered in the differential diagnosis of retinal vascular
      occlusive disorders in young patients. Combination therapy with systemic steroids
      and azathioprine are effective for maintenance of remission and prevention of
      ocular complications.

PMID- 25390376
TI  - Central retinal vein occlusion after intense exercise in healthy patients.
AB  - PURPOSE: To report a case-series of central retinal vein occlusion that occurred
      in young, healthy patients after periods of intense exercise. DESIGN:
      Retrospective chart review. METHODS: Seven eyes of six patients with central
      retinal vein occlusion after exercise were assessed. Visual acuity, intraocular
      pressure, and physical examination evidence of neovascularization were recorded
      on presentation and follow-up visits. Some patients had optical coherence
      tomography done on both initial and final visits and some had only one optical
      coherence tomography performed. One eye had no light perception at the time of
      diagnosis and was excluded from statistical calculations involving visual acuity.
      RESULTS: Patients were all males without any significant medical history. All
      patients had complete blood work, including hypercoagulable workup. Results were
      normal and no underlying cause was ever identified. Mean age was 37.6 years. The
      mean duration of symptoms before examination was 12.4 weeks. The average time
      that patients were observed was 170 days. On presentation, the average logarithm
      of the minimum angle of resolution value and standard deviation of visual acuity
      were 0.113 +/- 0.198. The decimal acuity at this time was 0.83 +/- 1.98 lines
      with the Snellen equivalent of 20/28.33 +/- 1.92 lines. The average logarithm of
      the minimum angle of resolution value and standard deviation of final visual
      acuity were 0.081 +/- 0.179. The decimal acuity was 0.9 +/- 1.79 lines and the
      Snellen equivalent was 20/25.6 +/- 1.79 lines. Mean intraocular pressure was 16.9
      with standard deviation of 6.025. Range of intraocular pressure was 7 to 30 mmHg.
      Central retinal thickness as measured by optical coherence tomography ranged from
      200 to 700 MUm. No complication developed as a result of central retinal vein
      occlusion during the follow-up period. CONCLUSION: Central retinal vein occlusion
      may occur in young, healthy patients after intense exercise. The exact
      precipitating event is unknown, but may be a combination of factors, including
      transiently increased intravascular and intraocular pressure, dehydration, and
      increased blood viscosity.

PMID- 25390377
TI  - Retinal arteriolar macroaneurysms and central retinal vein occlusion in a patient
      with complete pulmonary atresia.
AB  - PURPOSE: Retinopathy in cyanotic heart disease arises due to hypoxia and
      polycythaemia. We report the development of central retinal vein occlusion, and
      two arteriolar macroaneurysms in a normotensive patient with polycythaemia
      secondary to complete pulmonary atresia. METHOD: A 44-year-old woman with
      polycythaemia secondary to complete pulmonary atresia, presented with unilateral
      reduced vision of hand movements in the right eye. Ocular assessment and
      hematological investigations were performed. Management was conservative.
      RESULTS: Visual acuity was hand movements in the right eye, 6/5 in the left eye.
      Fundus assessment found right central retinal vein occlusion, and vessel
      tortuosity in the left eye. Hematological tests revealed an elevated red blood
      count, hemoglobin, heamatocrit, but normal plasma viscosity. Three months later,
      two arteriolar macroaneurysms developed in the left superotemporal arcade. Vision
      of 6/5 was retained in the left eye, hence no laser treatment was given.
      Subsequent follow-up revealed gradual involution of both macroaneurysms.
      CONCLUSION: Multiple retinal arteriolar macroaneurysms may occur in association
      with cyanotic heart disease such as pulmonary atresia. They appear to involute
      spontaneously, hence conservative management is appropriate.

PMID- 25390378
TI  - Retinal arteriovenous malformation presenting with retinal vein occlusion during
      pregnancy.
AB  - PURPOSE: To report the clinical course and treatment outcomes of a patient with a
      previously undiagnosed retinal arteriovenous malformation who developed retinal
      vein occlusions and cystoid macular edema during pregnancy. METHODS:
      Observational case report. RESULTS: A 26-year-old pregnant woman at 26 weeks'
      gestation with no medical history presented with decreased vision. On
      examination, a retinal arteriovenous malformation associated with multiple vein
      occlusions and cystoid macular edema was found in the affected eye. No
      intracranial arteriovenous malformations were found on neuroimaging. The patient
      was not immediately treated and cystoid macular edema persisted on subsequent
      follow-up visits. After the patient stopped breastfeeding, she was treated with a
      single intravitreal injection of 1.25 mg bevacizumab, which resulted in
      resolution of cystoid macular edema and improvement in visual acuity from 6/200
      to 20/200. CONCLUSION: The clinical course of retinal arteriovenous malformations
      may be altered by pregnancy and treatment with intravitreal Avastin (bevacizumab)
      may be beneficial for cystoid macular edema secondary to retinal vein occlusions
      in this setting.

PMID- 25390379
TI  - Embolectomy for branch retinal arterial occlusion.
AB  - PURPOSE: To report one surgeon's experience in treating a case of branch retinal
      artery occlusion with pars plana vitrectomy and surgical removal of the etiologic
      retinal arterial embolus. METHODS: Single case presentation of pre- and
      postoperative visual acuity data, fluorescein angiography, and optical coherence
      tomography studies of one eye undergoing pars plana vitrectomy and retinal
      arterial embolectomy. RESULTS: Attempted embolectomy was unsuccessful in removing
      the retinal arterial embolus. Intraoperatively, the embolus traveled retrograde
      back into the central retinal artery when the infusion bottle was raised to
      maximum height. On postoperative Day 1, the embolus had returned to its
      preoperative position. However, postoperative arterial perfusion improved, as
      evidenced by fluorescein angiography, and macular edema was improved on the first
      postoperative day, as documented on optical coherence tomography. Visual acuity
      improved from 20/80 preoperatively to 20/32 at 1 month and to 20/20 at 9 months
      postoperatively, even though the affected retinal tissue had markedly thinned.
      CONCLUSION: This single case illustrates our experience with the vitreous
      surgical techniques of embolus extraction in an eye with a branch retinal artery
      occlusion and an ophthalmoscopically visible embolus.

PMID- 25390380
TI  - Talc retinopathy presenting as multiple retinal arteriolar occlusions.
AB  - PURPOSE: To describe a patient with bilateral retinal arteriolar occlusions
      secondary to talc in the associated vessels resulting from intravenous drug use
      and a patent foramen ovale. METHODS: A 24-year-old woman presented with bilateral
      retinal arteriolar occlusions with visible foreign material in the associated
      vessels. A transesophageal echocardiogram showed a patent foramen ovale. A
      subsequent chest computed tomography angiogram showed a diffuse fine nodular
      pattern with focal nodules bilaterally and lung biopsy showed a foreign body
      giant cell reaction to polarizable material consistent with talc. This patient's
      patent foramen ovale allowed larger talc particles to enter her systemic
      circulation obstructing several retinal arterioles creating an atypical
      appearance of talc retinopathy. CONCLUSION: To our knowledge, this is only the
      second case report of talc causing arteriolar occlusions and displays the
      characteristic lung computed tomography angiogram and histopathologic findings
      associated with systemic talcosis.

PMID- 25390381
TI  - Bilateral talc maculopathy and fibrovascular proliferation in a drug abuser.
AB  - BACKGROUND: Intravenous drug abuse can cause a characteristic crystalline
      maculopathy. Very rarely, peripheral retinal neovascularization can also be seen
      in intravenous drug abusers. We present a case of a young cocaine abuser with
      bilateral crystalline maculopathy and peripheral retinal neovascularization.
      METHODS: Case report. RESULTS: Retinal vascular emboli such as talc are common in
      drug abusers, but in most cases, the retinal deposits pose only a minimal threat
      to vision. Our case shows a bilateral crystalline maculopathy and extensive
      retinal neovascularization, with a devastating effect on visual acuity.
      CONCLUSION: Intravenous drug abuse can cause retinopathy. This article is about a
      young cocaine abuser with bilateral crystalline maculopathy and extensive
      peripheral retinal neovascularization.

PMID- 25390382
TI  - Intravitreal triamcinolone and bevacizumab therapy for combined papillophlebitis
      and central retinal artery occlusion.
AB  - PURPOSE: To report a case of an idiopathic, unilateral combined central retinal
      artery and vein occlusion in a young, healthy patient successfully treated with
      combined intravitreal triamcinolone and bevacizumab injection. METHODS:
      Interventional case report. A 38-year-old man presented with a 2-hour history of
      acute painless loss of vision in his right eye. Ophthalmic examination revealed
      count fingers visual acuity, an afferent pupillary defect, a discreet cherry red
      spot, optic disk edema, and scattered intraretinal hemorrhages in the right
      fundus. Fluorescein angiography confirmed the central retinal artery occlusion
      diagnosis. RESULTS: A standard treatment for central retinal artery occlusion and
      a combined intravitreal triamcinolone and bevacizumab injection were performed.
      An exhaustive laboratory workup failed to reveal any evidence of systemic
      vascular, inflammatory, or hypercoagulable disorders. Transesophageal
      echocardiography, carotid Doppler, and magnetic resonance imaging of the orbits
      and brain were all unremarkable. In the month after initiation of the treatment,
      the patient's visual acuity gradually improved to 20/30 and remained stable
      during a 12-month follow up. CONCLUSION: Although the visual prognosis of a
      combined central retinal artery and vein occlusion is generally poor, our patient
      experienced an excellent visual recovery more than 1 month after prompt standard
      of care and a combined intravitreal triamcinolone and bevacizumab injection.
      Further investigation is necessary to support the efficacy and safety of this
      approach.

PMID- 25390383
TI  - Serous retinal detachment as a complication of acute posterior multifocal placoid
      pigment epitheliopathy.
AB  - PURPOSE: To report the occurrence and optical coherence tomography
      characteristics of serous retinal detachments in a patient with acute posterior
      multifocal placoid pigment epitheliopathy (APMPPE). METHODS: A patient with
      APMPPE presented with a dramatic reduction in vision associated with bilateral
      serous retinal detachments. RESULTS: After systemic steroid treatment, the serous
      detachments resolved leaving pigmentary changes typical of resolved APMPPE.
      CONCLUSION: Serous retinal detachments are an unusual finding in APMPPE. We
      describe an unusual case of APMPPE that has features typical of both APMPPE and
      Vogt-Koyanagi-Harada disease with optical coherence tomography characteristics
      that, to the authors' knowledge, have yet to be described in APMPPE.

PMID- 25390384
TI  - Inner retinal cleavage associated with idiopathic epiretinal membrane.
AB  - PURPOSE: To report a case of inner retinal cleavages that disappeared after
      idiopathic epiretinal membranes were removed. METHODS: A 72-year-old woman with
      epiretinal membranes and inner retinal cleavages in her nonmyopic eye underwent
      pars plana vitrectomy and epiretinal membrane removal. Fundus examination and
      optical coherence tomography were performed before and after surgery. RESULTS:
      Inner retinal cleavages disappeared after epiretinal membranes were removed.
      CONCLUSION: We postulate that the inner retinal cleavages are associated with
      tangential retinal tractions.

PMID- 25390385
TI  - Reopening of a macular hole after nd:yag laser capsulotomy in a vitrectomized
      eye.
AB  - PURPOSE: To describe a case of reopening of macular hole in a vitrectomized eye
      after Nd:YAG laser capsulotomy. METHODS: A 70-year-old man presented with a Stage
      3 macula hole 5 years previously with a vision of 6/24. RESULTS: The patient had
      a vitrectomy with perfluoropropane tamponade. The macula hole closed and vision
      improved to 6/12. Subsequently, the patient underwent cataract surgery. The
      patient required Nd:YAG laser capsulotomy 18 months later for posterior capsule
      opacification. Assessment before laser treatment revealed the macular hole had
      remained closed. Immediately postlaser, the patient reported noticing a distinct
      central scotoma and it was later confirmed that the macular hole had reopened. He
      had a repeat vitrectomy with internal limiting membrane peel and perfluoropropane
      tamponade. The macular hole closed and vision improved to 6/18. CONCLUSION: To
      date, this represents the first case reported in the literature of reopening of a
      macular hole after Nd:YAG laser capsulotomy in a vitrectomized eye. This
      implicates causes other than changes in the vitreous for reopening of the macular
      hole.

PMID- 25390386
TI  - Posterior uveal cleft and hypotony complicating insertion of a fluocinolone
      acetonide implant.
AB  - PURPOSE: To describe posterior uveal cleft and chronic hypotony occurring in
      association with a fluocinolone acetonide implant (Retisert) that was
      successfully treated by vitrectomy, removal of the implant, and cryotherapy.
      METHODS: A 57-year-old female patient with idiopathic uveitis, well-controlled
      with cyclosporine, developed chronic hypotony with maculopathy after insertion of
      a fluocinolone acetonide implant. Visual acuity in the affected eye was counting
      fingers, and intraocular pressure was 0 mmHg. Wound leakage, cyclodialysis cleft,
      and cyclitic membrane were excluded. Ultrasound biomicroscopy demonstrated a
      posterior uveal cleft at the site of implant, which was presumed to have created
      a channel for passage of intraocular fluid to the suprachoroidal space. The
      patient was treated with pars plana vitrectomy, removal of the implant,
      cryotherapy at the implant site, and intravitreal triamcinolone acetonide
      injection. RESULTS: The procedure was well tolerated. Intraoperative appearance
      suggested incarceration of the implant, which did not show on ultrasound
      biomicroscopy. Intraocular pressure was normalized 5 days after the surgery.
      Postoperative visual acuity improved to 20/200 at 2 weeks after the surgery and
      remained stable through 1 year of follow-up. Uveitis remains well controlled with
      cyclosporine at 1 year after the procedure. CONCLUSION: Posterior uveal cleft may
      cause hypotony as a complication of insertion of a fluocinolone acetonide
      implant. The ultrasound biomicroscopy is a crucial investigation to establish the
      diagnosis and to exclude other pathologies including cyclodialysis cleft and
      cyclitic membrane. It may fail to demonstrate incarceration of an implant,
      however. Proper surgical technique may prevent this complication.

PMID- 25390387
TI  - Serratia marcescens endophthalmitis after 20-gauge pars plana vitrectomy.
AB  - PURPOSE: To describe the first reported case of endophthalmitis after 20-gauge
      vitrectomy caused by Serratia marcescens. METHODS: Retrospective case report.
      RESULTS: An 86-year-old woman underwent a standard 20-gauge vitrectomy for repair
      of a chronic rhegmatogenous retinal detachment. All sclerotomies were sutured at
      the completion of the case. Within 2 days after surgery, she developed severe
      endophthalmitis. A bacterial culture of her aqueous sample was positive for S.
      marcescens. Despite the culture-demonstrated sensitivity of this organism to the
      antibiotics given intravitreally, systemically, and topically to treat this
      infection, her condition deteriorated, and she developed panophthalmitis, orbital
      cellulitis, a corneal ulcer, and eventual no light perception vision.
      CONCLUSIONS: This is the first reported case of S. marcescens endophthalmitis
      after vitrectomy surgery. Endophthalmitis caused by S. marcescens has a poor
      visual prognosis and may show an in vivo clinical resistance to antibiotic
      therapy regardless of in vitro culture sensitivities.

PMID- 25390388
TI  - Neurosensory retinal detachment of the macula in retinal phototoxicity documented
      by optical coherence tomography.
AB  - PURPOSE: To report a neurosensory detachment documented by optical coherence
      tomography in operating light microscope-induced retinal phototoxicity. METHODS:
      A 53-year-old man had a pars plana lensectomy, core vitrectomy, and posterior
      chamber sutured intraocular lens implantation in his right eye. The surgery
      lasted >3 hours. RESULTS: On postoperative Day 13, best-corrected visual acuity
      was 20/100. There was retinal pigment epithelial atrophy in the superior macula
      with subtle pigmentary clumping on its borders. Fluorescein angiography revealed
      staining in the area of retinal pigment epithelium atrophy with blockage of
      underlying choroidal fluorescence by the border hyperpigmentation in a pattern
      typical of phototoxicity. Optical coherence tomography documented a large,
      central neurosensory detachment. The central macular thickness was 731 MUm. Best
      corrected visual acuity in the right eye on postoperative Day 31 had improved to
      20/60, and the optical coherence tomography had minimal subretinal fluid with a
      central macular thickness of 226 MUm. On postoperative Day 78, there was no
      subretinal fluid, best-corrected visual acuity was 20/50, and the central macular
      thickness was 191 MUm. Four months postoperatively, best-corrected visual acuity
      was 20/30. CONCLUSION: Microscope light-induced retinal phototoxicity may be
      associated with a neurosensory detachment.

PMID- 25390389
TI  - New retinal findings in cherubism.
AB  - PURPOSE: To report three new retinal findings in a patient with cherubism.
      PARTICIPANT: An 18-year-old male patient. METHODS: Clinical examination and
      retinal scanning with spectral domain optical coherence tomography. RESULTS: The
      spectral domain optical coherence tomography revealed inner retinal striae in the
      posterior pole of both eyes and a subfoveal vitelliform deposit in the left eye.
      There was an inferior retinoschisis in the left eye. CONCLUSIONS: The inner
      retinal striae, subretinal vitelliform deposit, and retinoschisis extend the
      scale of retinal findings associated with orbital (facial) cherubism.

PMID- 25390390
TI  - Pigmentary maculopathy in two siblings with wolfram syndrome.
AB  - PURPOSE: To report pigmentary maculopathy in two siblings with Wolfram syndrome
      (WS), which is a rare neurodegenerative autosomal recessive disorder that
      predisposes the development of type 1 diabetes in association with progressive
      optic atrophy. METHODS: We describe the ophthalmologic presentation of two white
      siblings with WS. RESULTS: Two brothers from a nonconsanguineous family had
      clinical characteristics of WS with type 1 diabetes and progressive optic atrophy
      at the age of 7 years to 8 years. Maculopathy pigmentary was discovered at the
      age of 20 years in the elder brother and at the age of 18 years in the younger
      brother. Diabetic retinopathy was absent. WFS1 gene investigation revealed two
      different inactivating mutations. A mitochondrial DNA mutation was not found in
      either patient. CONCLUSION: Further study is needed to determine the prevalence
      of this clinical presentation.

PMID- 25390391
TI  - Bilateral nonsimultaneous visual loss associated with idiopathic arterial
      pulmonary hypertension.
AB  - PURPOSE: To report ischemic central retinal vein occlusion in one eye and
      recurrent serous retinal detachment in the other eye of a patient with idiopathic
      arterial pulmonary hypertension. METHODS: A 33-year-old woman was referred to our
      institution 2 months after an episode of central retinal vein occlusion in her
      right eye. She had arterial pulmonary hypertension for 2 years and was enrolled
      in a double-blind clinical trial of a novel vasodilator (bosentan) for arterial
      pulmonary hypertension. At presentation, corrected visual acuity was hand
      movements in the right eye and 20/20 in the left eye. Intraocular pressure was
      normal in both eyes. Fundoscopy showed an optic disk with blurred margins, venous
      engorgement, and diffuse intraretinal hemorrhages in the right eye. The left eye
      was unremarkable. An afferent relative pupillary defect was also noticed on
      examination. Fluorescein angiography and electroretinogram confirmed the
      diagnosis of ischemic central retinal vein occlusion. An intravitreal injection
      of bevacizumab was then performed in the right eye. RESULTS: The first day after
      injection, best-corrected visual acuity in the left eye fell to counting fingers
      and a serous detachment of the macula was detected. Oral acetazolamide was used,
      with prompt recovery of visual acuity in the left eye to 20/20 in 2 days. Another
      intravitreal injection of bevacizumab and panretinal photocoagulation were later
      performed in the right eye. Although visual acuity in the right eye improved to
      20/400 2 months after bevacizumab injection, neovascular glaucoma developed in
      this eye. Moreover, serous retinal detachment recurred in the left eye. Topical
      antiglaucomatous drugs, further panretinal photocoagulation, and a new
      intavitreal injection of bevacizumab in the right eye as well as another course
      of acetazolamide controlled these complications. Final visual acuity was stable
      at 20/300 in the right eye and 20/20 in the left eye 2 months thereafter with
      normalization of intraocular pressure under hypotensive drops. CONCLUSION:
      Arterial pulmonary hypertension is a rare entity, infrequently leading to
      decreased vision. This report emphasizes the prompt response to acetazolamide as
      therapy for recurrent retinal detachment in one eye as well as the use of
      bevacizumab for the treatment of ischemic central retinal vein occlusion in the
      other eye and as an adjuvant to panretinal photocoagulation for neovascular
      glaucoma, which later developed. The disease must be remembered in the possible
      etiology of central retinal vein occlusion and of serous retinal detachment in
      the young patient.

PMID- 25390392
TI  - Rhegmatogenous retinal detachment associated with myelinated nerve fibers: a case
      report.
AB  - PURPOSE: To report the management of a case of rhegmatogenous retinal detachment
      associated with myelinated nerve fibers. METHODS: A 7-year-old boy presented with
      decreased vision in the right eye for 3 months. Fundus examination revealed total
      retinal detachment with a large break within the myelinated nerve fibers in the
      right eye. The right eye underwent pars plana vitrectomy, encirclage, relaxing
      retinotomy, endolaser, and C3F8 injection. RESULTS: The retina remained attached
      at the 6-month follow-up with visual acuity of 6/18, N10. CONCLUSION: An area of
      the retina with myelinated nerve fiber is stiff and could potentially pose
      problems in retinal reattachment when a retinal break is located within the same
      area.

PMID- 25390393
TI  - Diffuse choroidal melanocytoma simulating melanoma in a child with ocular
      melanocytosis.
AB  - PURPOSE: To report a clinicopathologic correlation of an extensive, diffuse uveal
      melanocytoma (magnocellular nevus) simulating diffuse choroidal melanoma in a
      child. METHODS: Clinicopathologic report. RESULTS: A 14-year-old girl with
      congenital sector ocular melanocytosis was found to have progressive visual loss
      and a diffuse choroidal mass measuring 18 mm in basal dimension and 4 mm in
      thickness. There was overlying orange pigment and secondary retinal detachment.
      Diffuse choroidal melanoma was suspected, and the eye was enucleated.
      Histopathologically, the entire uveal tract was diffusely thickened because of a
      proliferation of benign cells typical of melanocytoma without evidence of
      melanoma. CONCLUSION: Diffuse uveal melanocytoma is a rare variant of ocular
      melanocytosis that can cause reduced vision, overlying orange pigment, and
      retinal detachment, resembling a diffuse choroidal melanoma.

PMID- 25390394
TI  - Response of choroidal leiomyoma to treatment with proton beam radiation.
AB  - PURPOSE: Uveal leiomyoma is a rare, benign smooth muscle neoplasm usually
      diagnosed only after local resection or enucleation. We describe a single
      interventional case report with clinicopathologic correlation of an intraocular
      leiomyoma responding to proton beam radiation. CASE REPORT: A 51-year-old woman
      presented with a choroidal mass in the left eye that was initially diagnosed as a
      choroidal melanoma. The neoplasm was treated with a total of 70 cobalt gray
      equivalents of external proton beam radiation in 5 fractions over 7 days.
      Biannual follow-up examinations over 3 years showed a funduscopically and
      ultrasonographically regressing tumor. The left eye was enucleated approximately
      3 years postradiotherapy because of progressively increasing pain secondary to
      elevated intraocular pressure from neovascular glaucoma. Microscopic and
      immunohistochemical examination of the mass revealed a choroidal neoplasm
      expressing smooth muscle antigens consistent with a uveal leiomyoma. CONCLUSION:
      Uveal leiomyoma appears to be responsive to proton beam radiation, and
      radiotherapy may serve as an alternative to primary enucleation or local
      resection. Additional studies are necessary to determine whether radiotherapy of
      smaller tumors might render better results for vision and globe preservation.

PMID- 25390395
TI  - Resolution of macular edema in radiation retinopathy after intravenous diuresis.
AB  - PURPOSE: To report resolution of bilateral macular edema secondary to radiation
      retinopathy after intravenous diuresis. METHODS: Observational case report,
      consisting of clinical examination, fluorescein angiography, and optical
      coherence tomography. RESULTS: A 38-year-old woman developed radiation
      retinopathy and severe macular edema secondary to whole brain radiation therapy
      for metastatic breast cancer. After diuresis with intravenous furosemide for
      pleural effusion, the bilateral macular edema resolved. CONCLUSION: In select
      patients, systemic diuresis may aid in resolving macular edema.

PMID- 25390396
TI  - Hepatocellular carcinoma metastatic to uvea.
AB  - PURPOSE: To describe a case of uveal metastasis secondary to hepatocellular
      carcinoma. METHODS: The authors present a 57-year-old man with known diagnosis of
      hepatocellular carcinoma, with progressive visual problems in his right eye. Work
      up including indirect ophthalmoscopic examination, ocular ultrasonography, and
      brain magnetic resonance imaging revealed a dome-shaped choroidal mass abutting
      the optic disk with surrounding shallow exudative retinal detachment. RESULTS: A
      fine-needle biopsy of the lesion confirmed the presence of malignant cells
      suggestive of metastatic disease from hepatocellular carcinoma. The patient was
      subsequently treated with brachytherapy. The patient died 3 weeks after the
      treatment due to pneumonia, which was felt to be unrelated to his ocular disease.
      CONCLUSION: This is a report of a very unusual case of hepatocellular carcinoma
      with metastasis to uveal tract.

PMID- 25390397
TI  - Histopathologically proven mucinous cystadenocarcinoma metastatic to the choroid.
AB  - PURPOSE: To report the first case of conventional transcleral choroidal biopsy in
      the diagnosis of ovarian carcinoma metastatic to the choroid and to summarize the
      published cases of ovarian carcinoma metastatic to the choroid. METHODS: Case
      report and Medline literature review. RESULTS: This is the tenth case reported in
      the literature and the only case that underwent conventional transcleral
      choroidal biopsy. Transcleral choroidal biopsy allowed the diagnosis of
      metastatic mucinous cystadenocarcinoma of the ovary. Choroidal metastases are not
      associated with central nervous system involvement; however, investigations may
      reveal distal boney or pulmonary metastases. CONCLUSION: Ovarian carcinoma rarely
      metastases to the choroid and unlike breast carcinoma, concurrent central nervous
      system disease has not been reported. When systemic investigations fail to reveal
      active intraperitoneal disease or distal metastases, the clinician should
      consider referral to an ocular oncology center for a choroidal biopsy.

PMID- 25390398
TI  - Histologic and immunohistochemical features of an epiretinal membrane overlying a
      combined hamartoma of the retina and retinal pigment epithelium.
AB  - PURPOSE: To present the histologic and immunohistochemical findings of an
      epiretinal membrane overlying a combined hamartoma of the retina and retinal
      pigment epithelium. METHODS: An interventional case report. RESULTS: A 17-year
      old healthy girl with a history of congenital cataract presented with a combined
      hamartoma of the retina and retinal pigment epithelium with prominent epiretinal
      membrane portion. Pars plana vitrectomy and membranectomy were performed, and the
      excised epiretinal membrane was submitted for routine histology and
      immunohistochemistry. Hematoxylin and eosin stain showed a monolayer of cells
      with an underlying basement membrane. Some of the nuclei were more epithelioid,
      consistent with retinal pigment epithelium (but without pigment in the
      cytoplasm), and other nuclei were more spindle-shaped, consistent with fibroglial
      elements. The initial immunostains suggested an admixture of retinal pigment
      epithelium and retinal elements. CONCLUSION: To the authors' knowledge, this is
      the first study to use immunohistochemistry to elucidate the composition of these
      membranes. Future studies investigating the immunohistochemical profile of
      combined hamartomas are necessary.

PMID- 25390399
TI  - Hypertensive optic neuropathy and choroidopathy in an 18-year-old woman with
      renal failure.
AB  - PURPOSE: To describe hypertensive optic neuropathy and choroidopathy caused by
      renal failure in an 18-year-old woman. METHODS: The clinical and angiographic
      findings of a young patient with hypertensive optic neuropathy and choroidopathy
      caused by hypertensive emergency secondary to renal failure are described.
      RESULTS: The patient's visual acuity, bilateral optic nerve swelling, and macular
      edema improved with blood pressure control. Several small areas of exudative
      retinal detachment remain. CONCLUSION: Accelerated or malignant hypertension is a
      common cause of bilateral optic nerve swelling and exudative retinal detachments.
      Treatment of systemic hypertension is essential in reversing the ocular
      manifestations of the condition.

PMID- 25390400
TI  - Paracentral retinal defects after vitrectomy for macular hole and their evolution
      over time.
AB  - PURPOSE: The aim of this article is to present paracentral defects after macular
      hole surgery with spectral optical coherence tomography and to discuss its
      influence on functional outcome. METHODS: The authors report a spectral optical
      coherence tomography documented case of paracentral retinal defects in a patient
      after macular hole surgery. A spectral optical coherence tomography device with
      an axial resolution of 3 MUm was used. The 3-dimensional examination scanned an
      area of 7 * 7 mm around the macula. Additionally HRT2, macular module scans were
      performed. RESULTS: A 70-year-old man underwent surgery for macular hole. Best
      corrected visual acuity was 0.2 for 2 years after surgery. Paracentral retinal
      defects, first observed 1 week after surgery, tended to decrease in size.
      CONCLUSION: Full-thickness paracentral retinal holes are a rare vitrectomy
      complication. In this study, we suggest that the cause of those defects can be
      internal limiting membrane peeling itself, with no component of direct mechanical
      trauma.

PMID- 25390401
TI  - The novel use of bevacizumab and photodynamic therapy in the treatment of best
      disease.
AB  - PURPOSE: To report on the novel use of bevacizumab (Avastin) in combination with
      photodynamic therapy (PDT) for the treatment of Best disease with choroidal
      neovascularization. METHODS: A 17-year-old girl with Best disease, choroidal
      neovascularization, and subretinal hemorrhage in the right eye was treated with
      bevacizumab and PDT. RESULTS: The use of bevacizumab and PDT was associated with
      a change in vision from counting fingers to 20/25 and was well tolerated by the
      patient. CONCLUSION: The use of bevacizumab and PDT in the management of Best
      disease seems to be a very effective method of treatment showing improvement in
      visual acuity.This is the first case to be reported in the literature of
      bevacizumab in combination with PDT for the treatment of choroidal
      neovascularization in Best disease.

PMID- 25390402
TI  - Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (irvan) syndrome
      associated with positive perinuclear antineutrophil cytoplasmic antibody (p
      anca).
AB  - PURPOSE: To describe an unusual case of idiopathic retinal vasculitis, aneurysms,
      and neuroretinitis syndrome associated with a positive perinuclear antineutrophil
      cytoplasmic antibody test. METHODS: This is an interventional case report. A 22
      year-old man with decreased vision underwent ophthalmoscopic, angiographic, and
      laboratory evaluation. The left eye underwent laser therapy due to circinate
      retinopathy and more severe involvement. RESULTS: Extensive systemic workup was
      negative. The only positive laboratory test was a positive perinuclear
      antineutrophil cytoplasmic antibody (1/40 dilution) detected by indirect
      immunofluorescence and enzyme-linked immunosorbent assay (positive for
      antimyeloperoxidase antibody). The patient was observed for 2 years. The disorder
      remained limited to the eyes, and further systemic workup was unrevealing;
      perinuclear antineutrophil cytoplasmic antibody titer remained positive. Vision
      remained stable in the treated eye and was slightly reduced in the untreated eye.
      CONCLUSION: Idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome
      may be suggestive of a retinal form of perinuclear antineutrophil cytoplasmic
      antibody-associated vasculitis.

PMID- 25390403
TI  - Acute retinal necrosis and cystic encephalomalacia in a premature neonate.
AB  - PURPOSE: To report a case of an infant born at 30 weeks gestational age (GA) who,
      at 37 weeks GA, presented with bilateral acute retinal necrosis (ARN) syndrome
      and herpes simplex virus (HSV) encephalomalacia. METHODS: Observational case
      report. RESULTS: A premature infant was found to have ARN based on dilated
      funduscopic examination and positive HSV serologies. Herpes simplex virus
      encephalomalacia was diagnosed base on magnetic resonance imaging (MRI).
      CONCLUSION: To our knowledge, this is the youngest reported patient with ARN.
      This case demonstrates that neonatal ARN may present with posterior chorioretinal
      lesions and highlights the importance of considering HSV infection of the central
      nervous system with MRI findings of cystic encephalomalacia.

PMID- 25390404
TI  - Spontaneous resolution of total retinal detachment in coats disease.
AB  - PURPOSE: To present a case of a child with total retinal detachment secondary to
      Coats disease who failed different treatment modalities and then had spontaneous
      resolution of the retinal detachment years later. METHODS: Case report. RESULTS:
      After progressing to total retinal detachment despite multimodality therapy with
      intravitreal bevacizumab and laser photocoagulation for advanced Coats disease,
      the patient was watched routinely for almost 2 years. On routine follow-up, he
      was noted to have complete resolution of the total retinal detachment with a
      completely flat retina. CONCLUSION: Resolution of advanced Coats disease with
      total retinal detachment rarely occurs.

PMID- 25390406
TI  - VibeComm: radio-free wireless communication for smart devices using vibration.
AB  - This paper proposes VibeComm, a novel communication method for smart devices
      using a built-in vibrator and accelerometer. The proposed approach is ideal for
      low-rate off-line communication, and its communication medium is an object on
      which smart devices are placed, such as tables and desks. When more than two
      smart devices are placed on an object and one device wants to transmit a message
      to the other devices, the transmitting device generates a sequence of vibrations.
      The vibrations are propagated through the object on which the devices are placed.
      The receiving devices analyze their accelerometer readings to decode incoming
      messages. The proposed method can be the alternative communication method when
      general types of radio communication methods are not available. VibeComm is
      implemented on Android smartphones, and a comprehensive set of experiments is
      conducted to show its feasibility. 

PMID- 25390405
TI  - A coumarin-based fluorescent probe as a central nervous system disease biomarker.
AB  - Homocysteine and methylmalonic acid are important biomarkers for diseases
      associated with an impaired central nervous system (CNS). A new chemoassay
      utilizing coumarin-based fluorescent probe 1 to detect the levels of homocysteine
      is successfully implemented using Parkinson's disease (PD) patients' blood serum.
      In addition, a rapid identification of homocysteine and methylmalonic acid levels
      in blood serum of PD patients was also performed using the liquid chromatography
      mass spectrometry (LC-MS). The results obtained from both analyses were in
      agreement. The new chemoassay utilizing coumarin-based fluorescent probe 1 offers
      a cost- and time-effective method to identify the biomarkers in CNS patients. 

PMID- 25390407
TI  - Privacy-preserving data aggregation in two-tiered wireless sensor networks with
      mobile nodes.
AB  - Privacy-preserving data aggregation in wireless sensor networks (WSNs) with
      mobile nodes is a challenging problem, as an accurate aggregation result should
      be derived in a privacy-preserving manner, under the condition that nodes are
      mobile and have no pre-specified keys for cryptographic operations. In this
      paper, we focus on the SUM aggregation function and propose two privacy
      preserving data aggregation protocols for two-tiered sensor networks with mobile
      nodes: Privacy-preserving Data Aggregation against non-colluded Aggregator and
      Sink (PDAAS) and Privacy-preserving Data Aggregation against Colluded Aggregator
      and Sink (PDACAS). Both protocols guarantee that the sink can derive the SUM of
      all raw sensor data but each sensor's raw data is kept confidential. In PDAAS,
      two keyed values are used, one shared with the sink and the other shared with the
      aggregator. PDAAS can protect the privacy of sensed data against external
      eavesdroppers, compromised sensor nodes, the aggregator or the sink, but fails if
      the aggregator and the sink collude. In PDACAS, multiple keyed values are used in
      data perturbation, which are not shared with the aggregator or the sink. PDACAS
      can protect the privacy of sensor nodes even the aggregator and the sink collude,
      at the cost of a little more overhead than PDAAS. Thorough analysis and
      experiments are conducted, which confirm the efficacy and efficiency of both
      schemes. 

PMID- 25390408
TI  - Constrained state estimation for individual localization in wireless body sensor
      networks.
AB  - Wireless body sensor networks based on ultra-wideband radio have recently
      received much research attention due to its wide applications in health-care,
      security, sports and entertainment. Accurate localization is a fundamental
      problem to realize the development of effective location-aware applications
      above. In this paper the problem of constrained state estimation for individual
      localization in wireless body sensor networks is addressed. Priori knowledge
      about geometry among the on-body nodes as additional constraint is incorporated
      into the traditional filtering system. The analytical expression of state
      estimation with linear constraint to exploit the additional information is
      derived. Furthermore, for nonlinear constraint, first-order and second-order
      linearizations via Taylor series expansion are proposed to transform the
      nonlinear constraint to the linear case. Examples between the first-order and
      second-order nonlinear constrained filters based on interacting multiple model
      extended kalman filter (IMM-EKF) show that the second-order solution for higher
      order nonlinearity as present in this paper outperforms the first-order solution,
      and constrained IMM-EKF obtains superior estimation than IMM-EKF without
      constraint. Another brownian motion individual localization example also
      illustrates the effectiveness of constrained nonlinear iterative least square
      (NILS), which gets better filtering performance than NILS without constraint. 

PMID- 25390409
TI  - iMuseumA: an agent-based context-aware intelligent museum system.
AB  - Currently, museums provide their visitors with interactive tour guide
      applications that can be installed in mobile devices and provide timely tailor
      made multimedia information about exhibits on display. In this paper, we argue
      that mobile devices not only could provide help to visitors, but also to museum
      staff. Our goal is to integrate, within the same system, multimedia tour guides
      with the management facilities required by museums. In this paper, we present
      iMuseumA (intelligent museum with agents), a mobile-based solution to customize
      visits and perform context-aware management tasks. iMuseumA follows an agent
      based approach, which makes it possible to interact easily with the museum
      environment and make decisions based on its current status. This system is
      currently deployed in the Museum of Informatics at the Informatics School of the
      University of Malaga, and its main contributions are: (i) a mobile application
      that provides management facilities to museum staff by means of sensing and
      processing environmental data; (ii) providing an integrated solution for
      visitors, tour guides and museum staff that allows coordination and communication
      enrichment among different groups of users; (iii) using and benefiting from group
      communication for heterogeneous groups of users that can be created on demand. 

PMID- 25390410
TI  - Filaggrin mutations in a Western siberian population and their association with
      atopic dermatitis in children.
AB  - We determined the frequencies of null mutations of the FLG gene--2282del4, R501X,
      R2447X, 3702delG, S3247X, and the 12-repeat allele (rs12730241)--among 460
      Caucasians of the city of Novosibirsk, Russia. The frequency was 17.7% for
      rs12730241, 2.73% for 2282del4, 0.22% for R501X, 0.33% for R2447X, and 0% for
      3702delG and S3247X in a western Siberian population. A case-control study showed
      that the deletion 2282del4 was associated with atopic dermatitis in children
      (odds ratio 7.01; p<0.001). The other mutations were not.

PMID- 25390411
TI  - Case reports and small case series: some comments and prejudices.

PMID- 25390412
TI  - Coats-like response in linear en coup de sabre scleroderma.
AB  - PURPOSE: To describe a Coats-like response and central nervous system vasculitis
      and its successful management in a patient presenting with en coup de sabre
      scleroderma. METHODS: Retrospective interventional case report. Chart review.
      RESULTS: A 20-year-old white male patient with en coup de sabre scleroderma on
      treatment with oral cyclophosphamide and prednisone for associated central
      nervous system inflammation presented with photopsias in the ipsilateral side of
      the scleroderma. A magnetic resonance imaging before presentation had shown
      lesions suggestive of localized central nervous system vasculitis. Ocular
      examination showed vitritis and multiple venous and arteriolar saccular
      dilatations with lipid exudation and subretinal fluid. These were treated with
      intravitreal bevacizumab, focal laser, and subtenon triamcinolone acetonide.
      After a year of follow-up, there was near resolution of the exudation and
      complete resolution of the vitreous inflammation, and the patient has been
      clinically stable with no visual loss. CONCLUSION: Coats-like response with
      ocular inflammation can be associated with central nervous system vasculitis in
      patients with linear scleroderma. Careful clinical evaluation and aggressive
      multipronged treatment are necessary to ensure a successful outcome.

PMID- 25390413
TI  - Bilateral fungal endophthalmitis masquerading as multifocal chorioretinitis.
AB  - PURPOSE: Spontaneous healing of ocular Candida infection is extremely rare, and
      early clinical manifestations may be misleading. This report explicates how to
      make the appropriate diagnosis when facing atypical presentation of the disease.
      METHODS AND PATIENTS: Case report. RESULTS: A 36-year-old woman presented with
      bilateral chorioretinitis. Intravenous drug abuse was not suspected, and a
      diagnosis of multifocal chorioretinitis was made. Oral corticosteroid treatment
      was started. Three months later, all previously seen lesions had healed on the
      right eye but had increased on the left with development of severe
      endophthalmitis. Microbiologic analysis of scalp pustules yielded Candida
      albicans. She underwent vitrectomy, intravitreous amphotericin B injection, and
      systemic fluconazole treatment. The uveitis responded well to this treatment
      regiment, but subsequent development of macular edema and retinal detachment in
      the left eye limited the final visual acuity to 20/200. Visual acuity remained
      20/20 on the right without any evidence of inflammation. CONCLUSION: This case
      demonstrates a broad range of potential outcomes after Candida endophthalmitis in
      the same patient, from very rare healing without antifungal treatment in one eye
      to severe panuveitis in the other eye. The delayed diagnosis in this case led to
      the inappropriate treatment with corticosteroids alone and delayed antifungal
      treatment. Early differentiation of Candida chorioretinitis from multifocal
      chorioretinitis is critical to final visual outcome.

PMID- 25390414
TI  - Retinal pigment epithelium tear in vogt-koyanagi-harada disease.
AB  - PURPOSE: The purpose of this study was to report a case of Vogt-Koyanagi-Harada
      disease causing large tears of the retinal pigment epithelium (RPE). METHODS:
      Case report and literature review. RESULTS: A 41-year-old woman presented with
      headache, tinnitus, and bilateral panuveitis with multiple serous retinal
      detachments. She was started on oral prednisone, and the inflammation and serous
      detachments subsided. However, 2 weeks later, she developed large RPE tears.
      CONCLUSION: Vogt-Koyanagi-Harada disease is an inflammatory disorder of the
      choroid; however, irregularities in the RPE have been noted, most recently with
      the use of spectral domain ophthalmic coherence tomography. The finding of RPE
      tear with resolution of serous retinal detachment may further implicate
      involvement of the RPE in the disease process.

PMID- 25390415
TI  - Orbital migration of gas in a case of colobomatous microphthalmos.
AB  - PURPOSE: The purpose of the study was to report a unique case that suggests a
      communication between a colobomatous eye and the orbit. METHODS: Case report.
      PATIENTS: Eleven-year-old girl. RESULTS: Gas moved from the vitreous cavity into
      the orbit during vitrectomy in a colobomatous microphthalmic eye. CONCLUSION: As
      this case suggests, there may be an occult connection through the coloboma and
      the surrounding extraocular tissue, possibly providing an additional etiology of
      subretinal fluid that can be associated with these congenital optic nerve
      disorders.

PMID- 25390416
TI  - An intravenous microdose of bevacizumab for the treatment of pigment epithelial
      detachment associated to age-related macular degeneration refractory to
      intravitreal bevacizumab: a case report.
AB  - PURPOSE: The purpose of this study was to report the visual and anatomical
      outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a
      vascularized pigment epithelial detachment (PED) associated with exudative age
      related macular degeneration refractory to several intravitreal bevacizumab
      injections. METHODS: Interventional case report and literature review. RESULT: A
      62-year-old female patient with a PED secondary to age-related macular
      degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of
      bevacizumab. Despite an initial response where the PED decreased in size, the
      subretinal fluid reabsorbed and the visual acuity improved; after the seventh
      injection, the PED started to grow in size again causing a drop in visual acuity.
      After an intravenous injection of 10 mg of bevacizumab, the patient experienced
      an improvement in visual acuity and a flattening of her PED. CONCLUSION: An
      intravenous injection of a microdose of bevacizumab appears to have resolved the
      PED with a sustained improvement of visual acuity.

PMID- 25390417
TI  - Spontaneous regression in a case of racemose haemangioma archer's type 2.
AB  - BACKGROUND: Racemose hemangioma of the retina is a benign arteriovenous
      communication that can occur as an isolated solitary lesion or as a component of
      the Wyburn-Mason syndrome. We report a case of a patient with an Archer's type 2
      arteriovenous malformation that spontaneously regressed. METHODS: A retrospective
      clinical chart review. RESULTS: A 20-year-old woman was diagnosed with racemose
      hemangioma, Archer's type 2 on her right eye, after a retinal arteriovenous
      communication located at 6 o'clock was found. She was followed-up for more than
      10 years in our service, always remaining asymptomatic. After this time,
      spontaneous vascular regression and fibrosis was noticed. CONCLUSION: Racemose
      hemangiomas are usually stationary lesions, but spontaneous asymptomatic
      regression can occur.

PMID- 25390418
TI  - Kyrieleis plaques associated with acute retinal necrosis from herpes simplex
      virus type 2.
AB  - PURPOSE: To present the case of a 19-year-old woman with acute retinal necrosis
      syndrome due to herpes simplex virus type 2, who developed segmental periarterial
      (Kyrieleis) plaques six and one half weeks into her clinical course. METHODS:
      Retrospective case report. PATIENTS: Single patient with the diagnosis of acute
      retinal necrosis syndrome. RESULTS: The patient's vitreous biopsy was positive by
      polymerase chain reaction for herpes simplex virus type 2. DISCUSSION: Kyrieleis
      plaques have been found in the setting of toxoplasmosis, tuberculosis, syphilis,
      rickettsial disease, herpes zoster virus, intraocular lymphoma, and idiopathic
      branch retinal artery occlusions. The differential diagnosis for these
      periarterial plaques should also include herpes simplex virus type 2.

PMID- 25390419
TI  - Central serous chorioretinopathy associated with narcolepsy.
AB  - PURPOSE: The purpose of this study was to describe a case of central serous
      chorioretinopathy (CSC) associated with narcolepsy. METHODS: Case report.
      RESULTS: A 34-year-old man was followed for persistent CSC in his left eye for
      more than 11 months. He did not have any known risk factors for CSC, including
      obstructive sleep apnea. However, he experienced disrupted sleep because of
      narcolepsy, which was inadequately treated. After 2 weeks of adequate treatment
      for his narcolepsy, fundus examination and optic coherence tomography
      demonstrated complete resolution of his CSC. CONCLUSION: As this case report
      suggests, overactivation of the hypothalamic-pituitary-adrenal axis and
      sympathetic nervous system, seen with disrupted and poor quality sleep, may
      contribute to the development of CSC. Risk factors for CSC should include sleep
      disorders that can lead to chronic sleep deprivation.

PMID- 25390420
TI  - Ocular prostate cancer metastasis treated with external beam radiation.
AB  - PURPOSE: The purpose of this study was to report a rare case of ocular metastasis
      from prostate cancer treated successfully with external beam radiation therapy.
      METHODS: Case report and literature review. PATIENT: A 60-year-old man with a
      history of metastatic castration-resistant prostate cancer presented with
      decreased visual acuity in the right eye. Ophthalmoscopic examination showed a
      choroidal mass with characteristic surface retinal pigment epithelium spots
      (leopard spots), consistent with a metastatic tumor. The patient was treated with
      external beam radiation therapy. He had a dramatic improvement in visual acuity
      within 4 weeks of completing radiation treatment. Two and half years from
      radiation treatment to the right eye, he has maintained excellent vision (20/20
      with best correction) in spite of systemic disease progression. CONCLUSION: Uveal
      metastasis is a rare cause of unexplained blurred vision in the setting of
      metastatic adenocarcinoma of prostate. Palliative external beam radiotherapy
      provides effective and durable relief of symptoms during treatment and is
      generally a well-tolerated regimen with low risk of long-term morbidity.

PMID- 25390421
TI  - Peculiar manifestation of macular telangiectasia type 2.
AB  - PURPOSE: The purpose of this study was to report two unusual cases of macular
      telangiectasia type 2 with pronounced asymmetric clinical presentations. PATIENTS
      AND METHODS: Two patients. Observational case study. RESULTS: Two patients
      presented with acute complaints of decreased vision and metamorphopsia in one
      eye. Each was found to have unilateral, juxtafoveal, subretinal
      neovascularization and minimal or no clinical evidence of macular telangiectasia
      type 2 in the fellow eye. In one patient, clinical and angiographic findings of
      macular telangiectasia type 2 were observed in the previously unaffected eye 13
      years after the initial presentation. CONCLUSION: Macular telangiectasia type 2
      is a bilateral condition, but in rare cases, significant asymmetry between the
      two eyes concerning disease severity can occur, potentially delaying diagnosis
      and management.

PMID- 25390422
TI  - Spontaneous resolution of subretinal lens fragment.
AB  - PURPOSE: To report the outcome of a case of subretinal lens fragment that was
      observed after vitreous surgery for a giant retinal tear. METHODS: Case report.
      The patient underwent vitreous surgery for a giant retinal tear; in the immediate
      postoperative period, a fragment of lens was observed in the subretinal space.
      RESULTS: The patient was managed with topical and systemic steroids alone. At a
      follow-up, 6 months later, the lens matter had absorbed. CONCLUSION: In the
      present case, the subretinal lens fragment showed complete resolution with
      conservative treatment, obviating the need for surgical intervention.

PMID- 25390423
TI  - Bleb-associated infections after intravitreal injection.
AB  - PURPOSE: The purpose of this study was to describe two cases of bleb-associated
      infections after intravitreal injection. METHODS: Case reports of two patients.
      Case 1: A 41-year-old man with choroidal neovascular membrane received
      intravitreal injections of ranibizumab. Case 2: A 56-year-old man with cystoid
      macular edema after retinal detachment surgery received intravitreal
      triamcinolone acetonide. RESULTS: In Case 1, the patient developed a culture
      negative blebitis 3 days after intravitreal ranibizumab and was treated with
      intravitreal, subconjunctival, and oral antibiotics. The infection resolved after
      3 weeks, with stable 20/100 vision and preservation of bleb function. In Case 2,
      a bleb-associated endophthalmitis (positive for Streptococcus pneumoniae)
      occurred 3 weeks after intravitreal triamcinolone acetonide, requiring repeated
      intravitreal antibiotics and two vitrectomy procedures to control the infection,
      with final vision of hand motions. CONCLUSION: Bleb-associated infections can be
      a complication of intravitreal injection. The potentially severe results of bleb
      associated endophthalmitis warrant monitoring in patients with previous
      trabeculectomy who undergo intravitreal injection therapies.

PMID- 25390424
TI  - Catastrophic antiphospholipid antibody syndrome and cocaine abuse associated with
      bilateral retinal vascular occlusions.
AB  - PURPOSE: To describe a case of bilateral central retinal vein occlusion and
      central retinal artery occlusion associated with antiphospholipid antibody
      syndrome and cocaine abuse. METHODS: A single case report of a 44-year-old woman
      with a history of cocaine abuse, vasculitis, and 3 spontaneous abortions who
      developed painless complete loss of vision in both eyes concurrently with
      progressive motor and sensory polyneuropathy. The patient underwent an extensive
      laboratory, radiographic, ophthalmologic, and pathologic workup. RESULTS:
      Diagnosis of catastrophic antiphospholipid antibody syndrome was made based on
      established clinical and laboratory criteria, including a positive Russell's
      viper venom test, history of three spontaneous abortions and evidence of
      microvascular and macrovascular venous occlusions, and multiorgan failure. Urine
      toxicology screen was positive for cocaine metabolites. Her clinical course was
      remarkable for progressive mononeuritis multiplex and quadriplegia. She had no
      light perception on presentation, and fundus examination revealed extensive
      preretinal, intraretinal, and subretinal hemorrhages. Fluorescein angiography
      revealed complete occlusion of central retinal arteriolar and venular flow and
      retinal hemorrhages in both eyes. CONCLUSION: Bilateral central retinal vein
      occlusion and central retinal artery occlusion have been rarely reported in the
      literature and are often associated with underlying thrombotic risk factors, such
      as antiphospholipid antibody syndrome. Workup for underlying hypercoagulability
      and/or cocaine use should be considered in atypical and bilateral cases of
      central vein or artery occlusion. In this case, bilateral central retinal artery
      and vein occlusions developed as manifestations of catastrophic antiphospholipid
      antibody syndrome, which has not been previously reported.

PMID- 25390425
TI  - Cavernous hemangioma associated with retinal macrovessels.
AB  - PURPOSE: The purpose of this study was to report two unusual cases of retinal
      cavernous hemangiomas in conjunction with retinal macrovessels. METHODS:
      Observational case study. Two patients with unilateral retinal cavernous
      hemangiomas and no signs or symptoms of systemic disease were evaluated with full
      ophthalmic examination and underwent fundus photography and fluorescein
      angiography. RESULTS: Patient 1 had 20/20 visual acuity bilaterally and a normal
      funduscopic examination of the right eye. The left eye showed diffuse clusters of
      saccular aneurysms associated with a dilated superotemporal venous arcade that
      crossed the horizontal raphe temporally. Patient 2 had 20/30 visual acuity in the
      right eye and 20/20 visual acuity in the left eye. Funduscopic examination of the
      left eye was normal, but the right eye demonstrated multiple clusters of saccular
      dilations along the course of a dilated inferior retinal vein that crossed the
      horizontal raphe temporally. On fluorescein angiography, both patients had fluid
      erythrocyte levels within the saccular aneurysms and areas of capillary
      nonperfusion anterior to the tumor. CONCLUSION: Retinal cavernous hemangioma is a
      rare hamartoma that is typically isolated. However, it may be associated with
      other major abnormalities of the retinal vascular pattern. The authors describe
      two unique cases of a retinal cavernous hemangioma in conjunction with a retinal
      macrovessel.

PMID- 25390426
TI  - Fibrin sealant in the treatment of retinal detachment in morning glory syndrome.
AB  - PURPOSE: To report the usage of fibrin sealant in the treatment of retinal
      detachment in morning glory syndrome. METHODS: A case report of an 8-year-old boy
      with a recent, macula-off, inferior, bullous retinal detachment associated to his
      morning glory syndrome that was first treated by a pneumatic retinopexy. The
      following day, his examination revealed a total retinal detachment and subretinal
      gas. The patient underwent a 25-gauge pars plana vitrectomy, incomplete peeling
      of the glial tuft, 360 degrees  laser photocoagulation around the peripapillary
      staphyloma, 20% perfluoropropane endotamponade, and fibrin sealant injection to
      temporarily plug the slitlike retinal break visualized on the inferior border of
      the peripapillary staphyloma. RESULTS: Complete reattachment of the retina
      persisted after 6 months of follow-up with slight improvement in visual acuity
      noted by the patient. CONCLUSION: The authors believe that the usage of fibrin
      sealant seems to be a useful alternative in cases of retinal detachment related
      to morning glory syndrome with deep posterior peripapillary staphyloma,
      especially when persistent residual traction is suspected.

PMID- 25390427
TI  - Innovative use of a magnetized pick for removal of an intraocular foreign body
      with 25-gauge transconjunctival sutureless vitrectomy.
AB  - BACKGROUND: Since being introduced in 2002, 25-gauge transconjunctival sutureless
      vitrectomy techniques continue to gain popularity among vitreoretinal surgeons
      and are being used in the management of increasingly complex surgical patients.
      METHODS: In this report, we report a patient in whom a magnetized 25-gauge
      intraocular pick was used to facilitate removal of a metallic intraocular foreign
      body with 25-gauge transconjunctival sutureless vitrectomy without enlarging a
      sclerotomy wound. RESULTS: The magnetized 25-gauge intraocular pick allowed for
      removal of the intraocular foreign body through a posterior capsulorhexis and a
      standard cataract wound. "In the bag" placement of the posterior chamber
      intraocular lens resulted in a perfectly reconstructed pseudophakic anterior
      segment. CONCLUSION: The authors suggest that a magnetized 25-gauge pick may be a
      useful adjunct in the management of selected patients with a magnetic intraocular
      foreign body.

PMID- 25390428
TI  - Ocular biopsy through external needle drainage for isolated bilateral ocular
      relapse of childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: Isolated ocular relapse of acute lymphoblastic leukemia is not
      commonly seen. Subretinal infiltration and exudative retinal detachment may not
      provide a positive vitreous biopsy for histopathologic confirmation. METHOD: We
      present a case of a 5-year-old male patient with acute lymphoblastic leukemia in
      remission, who presented with bilateral subretinal leukemic infiltrates and
      exudative retinal detachment. An ocular biopsy through external needle drainage
      histopathologically confirmed an ocular relapse of acute lymphoblastic leukemia.
      RESULTS: Isolated ophthalmic relapse of acute lymphoblastic leukemia can present
      as bilateral exudative retinal detachment with subretinal infiltration.
      CONCLUSION: External needle drainage of the subretinal fluid and subretinal
      infiltration can increase the diagnostic yield for histopathologic confirmation
      of the relapse.

PMID- 25390429
TI  - Peripapillary choroidal neovascularization in congenital retinoschisis.
AB  - PURPOSE: To report a case of peripapillary choroidal neovascularization (CNV)
      associated with congenital retinoschisis. METHODS: Case report. RESULTS: A 5-year
      old white boy presented with regressed peripapillary CNV in the right eye along
      with peripheral retinoschisis in the same eye. The left eye presented with
      macular, lamellar, and peripheral retinoschisis changes. Optical coherence
      tomography and fluorescein angiography confirmed the presence of regressed
      peripapillary CNV in the right eye and also revealed retinal nonperfusion within
      the peripheral retinoschisis cavity in the right eye. CONCLUSION: The authors
      report a case of peripapillary CNV associated with congenital retinoschisis. The
      authors hypothesize that peripheral retinal nonperfusion in the right eye may
      have contributed to the development of CNV in that eye.

PMID- 25390430
TI  - PERIPHERAL VASCULAR ABNORMALITIES IN beta-THALASSEMIA MAJOR DETECTED BY ULTRA
      WIDE-FIELD FUNDUS IMAGING.
AB  - PURPOSE: To describe peripheral retinal vascular abnormalities in two patients
      with beta-thalassemia major. METHODS: Visual acuity testing, slit-lamp
      biomicroscopy, dilated fundus examination, ultra wide-field fundus photography,
      and fluorescein angiography were performed in two consecutive patients with beta
      thalassemia major. RESULTS: Both patients had excellent visual acuity (20/20 and
      20/25). Anterior segment examination was unremarkable. There were no lenticular
      changes noted in either patient. Dilated fundus examination was only remarkable
      for peripheral neovascular changes with preretinal hemorrhage in one patient and
      white without pressure in the other patient. Ultra wide-field fluorescein
      angiography revealed peripheral ischemia, vascular remodeling, active
      neovascularization, and arteriovenous anastomosis at the junction of perfused and
      nonperfused peripheral retina. One patient had sea fan neovascularization with
      active vitreous hemorrhage requiring peripheral laser photocoagulation.
      CONCLUSION: As with patients with sickle cell disorder, patients with beta
      thalassemia major may require surveillance for peripheral vascular abnormalities,
      with treatment of these abnormalities before they result in permanent visual
      loss.

PMID- 25390431
TI  - Effects of intravitreal anti-vascular endothelial growth factor treatment on
      retinal vasculature in retinal vein occlusion as determined by ultra wide-field
      fluorescein angiography.
AB  - PURPOSE: To investigate both peripheral and central retinal vascular changes
      after intravitreal anti-vascular endothelial growth factor (VEGF) therapy in the
      setting of acute retinal vein occlusion (RVO). METHODS: Two patients with macular
      edema, one secondary to central RVO (CRVO) and one secondary to branch RVO
      (BRVO), underwent ultra wide-field (200 degrees ) photography and fluorescein
      angiography before and after a single intravitreal injection of an anti-VEGF
      agent. The patient with CRVO received an intravitreal injection of ranibizumab
      (0.5 mg/0.05 mL). The patient with BRVO received an intravitreal injection of
      bevacizumab (1.25 mg/0.05 mL). The eye with CRVO was reevaluated with ultra wide
      field photography and fluorescein angiography at 7 days and 35 days after
      treatment. The eye with BRVO was reevaluated with ultra wide-field photography
      and fluorescein angiography at 30 days after treatment. Photographs and
      fluorescein angiographic results were analyzed for posttreatment changes in
      arteriovenous transit time, vessel caliber, vessel leakage, peripheral capillary
      nonperfusion, retinal hemorrhages, and nerve fiber layer infarcts. RESULTS: In
      both eyes, there were no changes detected in the arteriovenous transit time or
      peripheral capillary nonperfusion after anti-VEGF therapy. A reduction in
      intraretinal hemorrhages and nerve fiber layer infarcts was observed at 7 days
      and 35 days after treatment in the patient with CRVO and at 30 days after
      treatment in the patient with BRVO. A decrease in vessel caliber was observed at
      7 days after treatment in the patient with CRVO and at 30 days after treatment in
      the patient with BRVO. In the patient with CRVO, an increase in vessel caliber
      with a recurrence of vascular leakage was noted at the visit on Day 35.
      CONCLUSION: Anti-VEGF therapy in the setting of RVO may initially decrease vessel
      caliber, retinal hemorrhages, and nerve fiber layer infarcts but does not appear
      to affect arteriovenous transit time or areas of peripheral capillary
      nonperfusion after a single treatment. The beneficial effects of anti-VEGF
      therapy in RVO appear transient, and multiple injections may be required for
      control of macular edema. Ultra wide-field angiography can be a useful tool in
      monitoring the treatment of RVO.

PMID- 25390432
TI  - Successful treatment of toxoplasmosis-associated choroidal neovascular lesions
      with bevacizumab and antiparasitic therapy.
AB  - PURPOSE: To report the effects of oral trimethoprim/sulfamethoxazole and
      intravitreal bevacizumab injection in the treatment of ocular toxoplasmosis
      associated choroidal neovascular lesions (CNV). METHODS: This was a
      noncomparative, nonrandomized, consecutive case series. All eyes with ocular
      toxoplasmosis-associated CNV received one intravitreal bevacizumab injection
      under the coverage of oral trimethoprim/sulfamethoxazole. The changes in best
      corrected visual acuity were recorded. Serial fundus photography, fluorescein
      angiography, optical coherence tomography, and indocyanine green angiography were
      performed to measure the treatment efficacy. RESULTS: Three eyes of two patients
      with a history of ocular toxoplasmosis had active CNV demonstrated by fluorescein
      angiography and optical coherence tomography. Each was treated with oral
      trimethoprim/sulfamethoxazole and one intravitreal bevacizumab injection. Best
      corrected visual acuity, fundus photographs, fluorescein angiography, optical
      coherence tomography, and indocyanine green angiography all showed favorable
      results. No ocular or systemic complications were noted. In all three eyes, the
      CNV subsided and vision improved. CONCLUSION: Oral trimethoprim/sulfamethoxazole
      is an effective and less expensive antibiotic against Toxoplasma gondii.
      Intravitreal bevacizumab injection appears to be a well-tolerated treatment for
      toxoplasmosis-associated CNV and has the potential as an adjuvant therapy to
      improve final vision. More cases and further studies are required.

PMID- 25390433
TI  - Radiation maculopathy after epimacular brachytherapy for the treatment of
      subfoveal choroidal neovascularization secondary to age-related macular
      degeneration.
AB  - PURPOSE: To describe a case of radiation maculopathy after a 24-Gy single
      fraction epimacular brachytherapy delivered concomitantly with ranibizumab for
      the treatment of age-related macular degeneration. METHODS: Case report. RESULTS:
      An 82-year-old man with neovascular age-related macular degeneration was treated
      with epiretinal brachytherapy and 2 intraocular injections of ranibizumab with
      initial good response. Nineteen months after initial treatment, visual acuity
      decreased and the patient was diagnosed of radiation maculopathy. CONCLUSION:
      Radiation-related ocular side effects such as maculopathy may become evident
      several years after the treatment. Thus, vascular abnormalities that may appear
      in the follow-up of these patients can easily be misdiagnosed as a complication
      of the previous choroidal neovascularization.

PMID- 25390434
TI  - Branch retinal arterial occlusion treated with intravenous prostaglandin e1 and
      steroids.
AB  - PURPOSE: To present the use of 6-methylprednisolone IV and prostaglandin E1 IV, a
      powerful vasodilator of the microcirculation, in the treatment of a branch
      retinal arterial occlusion. METHODS: A 63-year-old man presented with a 3-hour
      history of a sudden loss of vision in the right eye. On ophthalmic examination,
      the diagnosis of a superior temporal branch retinal arterial occlusion was made.
      The patient was immediately given 40 mg of 6-methylprednisolone IV for more than
      5 minutes followed by 80 MUg of prostaglandin E1 with 2 milliequivalents of
      potassium IV for more than 3 hours. The same treatment was repeated the following
      morning. RESULTS: The visual acuity in the right eye improved from 2/10 at
      presentation to 7/10 at the end of the second day of treatment. Clinically, there
      was a reduction of the posterior pole edema. Eleven days after treatment, the
      visual acuity was 9/10 with no retinal edema. CONCLUSION: Immediate prostaglandin
      E1 IV and steroids should be considered in cases of recent-onset branch retinal
      arterial occlusion to restore retinal blood flow and improve visual acuity.

PMID- 25390435
TI  - Spectral-domain optical coherence tomography assessment of an epiretinal membrane
      with axoplasmic stasis from nerve fiber layer traction.
AB  - PURPOSE: To report a case of visible axoplasmic stasis on fundus examination
      correlating with spectral-domain optical coherence tomography findings of nerve
      fiber layer traction. METHODS: Case report. RESULTS: Spectral-domain optical
      coherence tomography images show nerve fiber layer traction and distortion at the
      sites where visible cotton wool spot-like changes were seen on examination. These
      visible changes are likely because of axoplasmic stasis from the severe traction
      on the nerve fiber layer. CONCLUSION: Spectral-domain optical coherence
      tomography demonstrates that cotton wool spot-like changes may be caused by nerve
      fiber layer traction in some epiretinal membranes. This is of interest in
      understanding the pathophysiology of these changes.

PMID- 25390436
TI  - Multifocal choroiditis secondary to the reactivation of epstein-barr virus.
AB  - PURPOSE: To describe a case of multifocal choroiditis associated with Epstein
      Barr virus reactivation in a patient who had previously had documented infectious
      mononucleosis. METHODS: Color photos, fluorescein angiography, autofluorescence,
      indocyanine green angiography, and high-definition optical coherence tomography
      imaging was performed. A 39-year-old woman presented with a central scotoma in
      her left eye. At 19 years of age, she developed a peripapillary choroidal
      neovascular complex in her right eye, which was treated by laser
      photocoagulation. Two weeks before her visual complaint, she suffered from a
      frontal headache, occipital lymphadenopathy, and splenomegaly. RESULTS:
      Laboratory studies revealed markedly elevated immunoglobulin G titers to Epstein
      Barr virus and she recalled a history of infectious mononucleosis at 20 years of
      age. CONCLUSION: While primary infection may manifest as infectious
      mononucleosis, like other viruses in the herpes virus family, there may be
      reactivation of the virus later in life.

PMID- 25390437
TI  - The role of intravenous immunoglobulin in treatment of acute retinal necrosis.
AB  - PURPOSE: To describe a case of successful treatment of acute retinal necrosis
      with a combination of antivirals and intravenous immunoglobulin. METHODS: This is
      a case report of a 77-year-old white man diagnosed with unilateral acute retinal
      necrosis. RESULTS: Combination therapy with systemic antivirals, prophylactic
      laser retinopexy, and intravenous immunoglobulin halted progression of retinitis
      and preserved visual acuity. CONCLUSION: Acute retinal necrosis is an aggressive
      disease with significant risk of vision loss even when treated with appropriate
      therapy. In this report, the authors describe a case of successful treatment with
      a combination of systemic antivirals and intravenous immunoglobulin. Intraocular
      antiviral injection plus systemic treatment remain to be a more cost-effective
      option.

PMID- 25390438
TI  - Chronic myelogenous leukemia and retinopathy treated with imatinib.
AB  - PURPOSE: To describe a case of a rapid clinical response to treatment of leukemic
      retinopathy and optic nerve infiltration with cytoreductive therapy, including
      imatinib mesylate (Gleevec), without radiation therapy. METHODS: Observational
      case report. RESULTS: A 13-year-old boy presented with blurry vision and a visual
      acuity of 20/20 in each eye. On examination, he had infiltrative retinopathy and
      optic nerve elevation bilaterally. Further testing revealed chronic myelogenous
      leukemia with severe leukocytosis. The results of the bone marrow biopsy showed
      the Philadelphia chromosome, t(9;22), which indicated he might respond to
      imatinib. He was treated with leukopheresis, followed by systemic imatinib and
      hydroxyurea, and his leukemic retinopathy and optic neuropathy quickly improved.
      CONCLUSION: This case demonstrates an excellent clinical response to systemic
      therapy, including imatinib, without urgent radiation. It is possible, in select
      cases, to consider treatment with systemic cytoreductive therapy in patients with
      infiltrative optic neuropathy and retinopathy with the Philadelphia chromosome.

PMID- 25390439
TI  - Surgical technique for the placement of an encircling scleral buckle in the
      presence of a glaucoma drainage device.
AB  - PURPOSE: The purpose of this study was to present a new surgical technique that
      facilitates placement of an encircling scleral buckle in a patient with a
      previously placed Baerveldt glaucoma implant who developed a retinal detachment
      due to a giant retinal tear. METHODS: Case report of patient with previous
      Baerveldt glaucoma implant and a retinal detachment associated with a giant
      retinal tear who was managed with an encircling scleral buckle and pars plana
      vitrectomy. The encircling band was attached to the Baerveldt glaucoma implant to
      incorporate as a component of the encircling scleral buckle. RESULTS:
      Reattachment with typical encircling effect without intraocular pressure
      complications was achieved. CONCLUSION: This technique offers an option for
      management of retinal detachment in the presence of a Baerveldt glaucoma implant.

PMID- 25390456
TI  - GA to HbA1C ratio, but not HbA1C is associated with cognition in Chinese
      nondiabetic old adults.
AB  - OBJECTIVES: To investigate the relationship between glycated albumin (GA) to
      glycated hemoglobin (HbA1c) ratio and cognitive impairment in old age. Diabetes
      is associated with cognitive impairment in older people. However, the link
      between elevated GA/HbA1c levels and the risk of cognitive impairment in
      nondiabetic individuals is unclear. METHODS: A cross-sectional study of 474 old,
      nondiabetic adults (192 women, mean age 73.8 years +/- 6.9 SD) who had been
      admitted to our hospital was conducted. Glycemic measures included fasting plasma
      glucose (FPG), 2-hour post-prandial plasmic glucose (2hPPG), GA and HbA1c.
      Cognitive function was assessed using Mini-Mental State Examination (MMSE) and
      Montreal Cognitive Assessment (MoCA) at the same examination visit in which the
      glycemic measures were determined. RESULTS: When the individuals were divided
      into two groups according to the median of GA/HbA1c ratio, old adults with
      GA/HbA1c ratio >= 2.53 showed lower MMSE and MoCA scores compared to those with
      GA/HbA1c ratio < 2.53. Univariate regression analysis showed that MMSE and MoCA
      scores were not correlated with HbA1c, but were inversely correlated with GA and
      GA/HbA1c ratio. Linear regression analysis revealed that there was a significant
      negative correlation between GA/HbA1c and cognitive function (beta = -0.77, P <
      0.01 for MoCA and beta = -0.69, P < 0.05 for MMSE) even after adjustment for age,
      body mass index, systolic blood pressure, lipoprotein(a) and sex. CONCLUSION: Our
      results indicate that even in the absence of manifest type 2 diabetes mellitus,
      GA/HbA1c ratio levels exert a negative influence on cognition and it may be a
      better predictor for cognitive impairment in the older population.

PMID- 25390455
TI  - Intravenous thiamine is associated with increased oxygen consumption in
      critically ill patients with preserved cardiac index.
AB  - RATIONALE: Oxygen consumption may be impaired in critically ill patients.
      OBJECTIVES: To evaluate the effect of intravenous thiamine on oxygen consumption
      ([Formula: see text]o2) in critically ill patients. METHODS: This was a small,
      exploratory open-label pilot study conducted in the intensive care units at a
      tertiary care medical center. Critically ill adults requiring mechanical
      ventilation were screened for enrollment. Oxygen consumption ([Formula: see
      text]o2) and cardiac index (CI) were recorded continuously for 9 hours. After 3
      hours of baseline data collection, 200 mg of intravenous thiamine was
      administered. The outcome was change in [Formula: see text]o2 after thiamine
      administration. MEASUREMENTS AND MAIN RESULTS: Twenty patients were enrolled and
      3 were excluded because of incomplete [Formula: see text]o2 data, leaving 17
      patients for analysis. There was a trend toward increase in [Formula: see text]o2
      after thiamine administration (16.3 ml/min, SE 8.5; P = 0.052). After preplanned
      adjustment for changes in CI in case of a delivery-dependent state in some
      patients (with exclusion of one additional patient because of missing CI data),
      this became statistically significant (16.9 ml/min, SE 8.6; P = 0.047). In
      patients with average CI greater than our cohort's mean value of 3 L/min/m(2),
      [Formula: see text]o2 increased by 70.9 ml/min (+/-16; P < 0.0001) after
      thiamine. Thiamine had no effect in patients with reduced CI (< 2.4 L/min/m(2)).
      There was no association between initial thiamine level and change in [Formula:
      see text]o2 after thiamine administration. CONCLUSIONS: The administration of a
      single dose of thiamine was associated with a trend toward increase in [Formula:
      see text]o2 in critically ill patients. There was a significant increase in
      [Formula: see text]o2 in those patients with preserved or elevated CI. Further
      study is needed to better characterize the role of thiamine in oxygen extraction.
      Clinical trial registered with www.clinicaltrials.gov (NCT01462279).

PMID- 25390457
TI  - Evaluation of muscular activity duration in shoulders with rotator cuff tears
      using inertial sensors and electromyography.
AB  - Shoulder disorders, including rotator cuff tears, affect the shoulder function
      and result in adapted muscle activation. Although these adaptations have been
      studied in controlled conditions, free-living activities have not been
      investigated. Based on the kinematics measured with inertial sensors and portable
      electromyography, the objectives of this study were to quantify the duration of
      the muscular activation in the upper trapezius (UT), medial deltoid (MD) and
      biceps brachii (BB) during motion and to investigate the effect of rotator cuff
      tear in laboratory settings and daily conditions. The duration of movements and
      muscular activations were analysed separately and together using the relative
      time of activation (T(EMG/mov)). Laboratory measurements showed the parameter's
      reliability through movement repetitions (ICC > 0.74) and differences in painful
      shoulders compared with healthy ones (p < 0.05): longer activation for UT; longer
      activation for MD during abduction and tendency to shorter activation in other
      movements; shorter activation for BB. In daily conditions, T(EMG/mov) for UT was
      longer, whereas it was shorter for MD and BB (p < 0.05). Moreover, significant
      correlations were observed between these parameters and clinical scores. This
      study thus provides new insights into the rotator cuff tear effect on duration of
      muscular activation in daily activity.

PMID- 25390458
TI  - The concept of risk in comparative-effectiveness research.

PMID- 25390459
TI  - OHRP and standard-of-care research.

PMID- 25390461
TI  - Out of Africa--caring for patients with Ebola.

PMID- 25390460
TI  - Clinical care of two patients with Ebola virus disease in the United States.
AB  - West Africa is currently experiencing the largest outbreak of Ebola virus disease
      (EVD) in history. Two patients with EVD were transferred from Liberia to our
      hospital in the United States for ongoing care. Malaria had also been diagnosed
      in one patient, who was treated for it early in the course of EVD. The two
      patients had substantial intravascular volume depletion and marked electrolyte
      abnormalities. We undertook aggressive supportive measures of hydration
      (typically, 3 to 5 liters of intravenous fluids per day early in the course of
      care) and electrolyte correction. As the patients' condition improved clinically,
      there was a concomitant decline in the amount of virus detected in plasma. 

PMID- 25390463
TI  - Adverse drug reactions associated with antiretroviral therapy during pregnancy.
AB  - INTRODUCTION: Antiretroviral (ARV) drug use during pregnancy significantly
      reduces mother-to-child HIV transmission, delays disease progression in the women
      and reduces the risk of HIV transmission to HIV-serodiscordant partners. Pregnant
      women are susceptible to the same adverse reactions to ARVs as nonpregnant adults
      as well as to specific pregnancy-related reactions. In addition, we should
      consider adverse pregnancy outcomes and adverse reactions in children exposed to
      ARVs during intrauterine life. However, studies designed to assess the safety of
      ARV in pregnant women are rare, usually with few participants and short follow-up
      periods. AREAS COVERED: In this review, we discuss studies reporting adverse
      reactions to ARV drugs, including maternal toxicity, adverse pregnancy outcomes
      and the consequences of exposure to ARV in infants. We included results of
      observational studies, both prospective and retrospective, as well as randomized
      clinical trials, systematic reviews and meta-analyses. EXPERT OPINION: The
      benefits of ARV use during pregnancy outweigh the risks of adverse reactions
      identified to date. More studies are needed to assess the adverse effects in the
      medium- and long term in children exposed to ARVs during pregnancy, as well as
      pregnant women using lifelong antiretroviral therapy and more recently available
      drugs.

PMID- 25390464
TI  - Removal of a penetrating orbital and anterior fossa foreign body using an eyebrow
      incision.
AB  - In this case, we present an underutilised eyebrow approach for removing
      penetrating foreign bodies of the orbit extending into the anterior fossa floor.
      Excellent visualisation of the sub-frontal region is achieved and a large trauma
      craniotomy is avoided, but care must be taken to preserve the supra-orbital and
      fronto-temporal nerves. 

PMID- 25390466
TI  - Earlier palliative care for oncology patients: walking a fine line.

PMID- 25390462
TI  - Inactivating mutations in NPC1L1 and protection from coronary heart disease.
AB  - BACKGROUND: Ezetimibe lowers plasma levels of low-density lipoprotein (LDL)
      cholesterol by inhibiting the activity of the Niemann-Pick C1-like 1 (NPC1L1)
      protein. However, whether such inhibition reduces the risk of coronary heart
      disease is not known. Human mutations that inactivate a gene encoding a drug
      target can mimic the action of an inhibitory drug and thus can be used to infer
      potential effects of that drug. METHODS: We sequenced the exons of NPC1L1 in 7364
      patients with coronary heart disease and in 14,728 controls without such disease
      who were of European, African, or South Asian ancestry. We identified carriers of
      inactivating mutations (nonsense, splice-site, or frameshift mutations). In
      addition, we genotyped a specific inactivating mutation (p.Arg406X) in 22,590
      patients with coronary heart disease and in 68,412 controls. We tested the
      association between the presence of an inactivating mutation and both plasma
      lipid levels and the risk of coronary heart disease. RESULTS: With sequencing, we
      identified 15 distinct NPC1L1 inactivating mutations; approximately 1 in every
      650 persons was a heterozygous carrier for 1 of these mutations. Heterozygous
      carriers of NPC1L1 inactivating mutations had a mean LDL cholesterol level that
      was 12 mg per deciliter (0.31 mmol per liter) lower than that in noncarriers
      (P=0.04). Carrier status was associated with a relative reduction of 53% in the
      risk of coronary heart disease (odds ratio for carriers, 0.47; 95% confidence
      interval, 0.25 to 0.87; P=0.008). In total, only 11 of 29,954 patients with
      coronary heart disease had an inactivating mutation (carrier frequency, 0.04%) in
      contrast to 71 of 83,140 controls (carrier frequency, 0.09%). CONCLUSIONS:
      Naturally occurring mutations that disrupt NPC1L1 function were found to be
      associated with reduced plasma LDL cholesterol levels and a reduced risk of
      coronary heart disease. (Funded by the National Institutes of Health and
      others.).

PMID- 25390467
TI  - Clinician roles in early integrated palliative care for patients with advanced
      cancer: a qualitative study.
AB  - BACKGROUND: Early palliative care provides better quality of life, increased
      prognostic awareness, and even improved survival for patients with advanced
      cancer but how the integrated care model achieves these outcomes has not been
      completely explained. METHODS: To better understand the clinical approach to
      early outpatient care from the clinicians' perspective, we conducted focus groups
      with the palliative care clinicians who had participated in a randomized trial of
      early palliative care for metastatic lung cancer. RESULTS: Clinicians described
      their role in providing early palliative care as having three distinct roles in
      the outpatient setting: (1) managing symptoms to improve functional status and as
      a bridge to other issues; (2) engaging patients in emotional work to facilitate
      coping, accepting, and planning; and (3) interpreting the oncologist for the
      patient and the patient for the oncologist. CONCLUSIONS: These data lay the
      foundation for developing training programs for clinicians in early integrated
      palliative care.

PMID- 25390469
TI  - The strength beyond the muscle.

PMID- 25390468
TI  - Integration of palliative care in end-stage liver disease and liver
      transplantation.
AB  - BACKGROUND: Patients with end-stage liver disease (ESLD) have a life-limiting
      illness that causes multiple distressing symptoms and negatively affects quality
      of life (QOL). This population traditionally has not had much attention within
      the palliative care community. DISCUSSION: This article provides an evidence
      based review of palliative care issues that patients with ESLD and those awaiting
      liver transplant face, including approaches to prognosis, symptom management,
      advance care planning, and end-of-life care. CONCLUSION: Tremendous opportunity
      exists to integrate palliative medicine into the care of these patients.

PMID- 25390470
TI  - The forgotten meaning.

PMID- 25390471
TI  - Theoretical analysis of microtubule dynamics at all times.
AB  - Microtubules are biopolymers consisting of tubulin dimer subunits. As a major
      component of cytoskeleton they are essential for supporting most important
      cellular processes such as cell division, signaling, intracellular transport and
      cell locomotion. The hydrolysis of guanosine triphosphate (GTP) molecules
      attached to each tubulin subunit supports the nonequilibrium nature of
      microtubule dynamics. One of the most spectacular properties of microtubules is
      their dynamic instability when their growth from continuous attachment of tubulin
      dimers stochastically alternates with periods of shrinking. Despite the critical
      importance of this process to all cellular activities, its mechanism remains not
      fully understood. We investigated theoretically microtubule dynamics at all times
      by analyzing explicitly temporal evolution of various length clusters of
      unhydrolyzed subunits. It is found that the dynamic behavior of microtubules
      depends strongly on initial conditions. Our theoretical findings provide a
      microscopic explanation for recent experiments which found that the frequency of
      catastrophes increases with the lifetime of microtubules. It is argued that most
      growing microtubule configurations cannot transit in one step into a shrinking
      state, leading to a complex overall temporal behavior. Theoretical calculations
      combined with Monte Carlo computer simulations are also directly compared with
      experimental observations, and good agreement is found. 

PMID- 25390472
TI  - Mesenchymal stem cells support neuronal fiber growth in an organotypic brain
      slice co-culture model.
AB  - Mesenchymal stem cells (MSCs) have been identified as promising candidates for
      neuroregenerative cell therapies. However, the impact of different isolation
      procedures on the functional and regenerative characteristics of MSC populations
      has not been studied thoroughly. To quantify these differences, we directly
      compared classically isolated bulk bone marrow-derived MSCs (bulk BM-MSCs) to the
      subpopulation Sca-1(+)Lin(-)CD45(-)-derived MSCs(-) (SL45-MSCs), isolated by
      fluorescence-activated cell sorting from bulk BM-cell suspensions. Both
      populations were analyzed with respect to functional readouts, that are,
      frequency of fibroblast colony forming units (CFU-f), general morphology, and
      expression of stem cell markers. The SL45-MSC population is characterized by
      greater morphological homogeneity, higher CFU-f frequency, and significantly
      increased nestin expression compared with bulk BM-MSCs. We further quantified the
      potential of both cell populations to enhance neuronal fiber growth, using an ex
      vivo model of organotypic brain slice co-cultures of the mesocortical
      dopaminergic projection system. The MSC populations were cultivated underneath
      the slice co-cultures without direct contact using a transwell system. After
      cultivation, the fiber density in the border region between the two brain slices
      was quantified. While both populations significantly enhanced fiber outgrowth as
      compared with controls, purified SL45-MSCs stimulated fiber growth to a larger
      degree. Subsequently, we analyzed the expression of different growth factors in
      both cell populations. The results show a significantly higher expression of
      brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor in
      the SL45-MSCs population. Altogether, we conclude that MSC preparations enriched
      for primary MSCs promote neuronal regeneration and axonal regrowth, more
      effectively than bulk BM-MSCs, an effect that may be mediated by a higher BDNF
      secretion. 

PMID- 25390473
TI  - Rehabilitation of meniscal injury and surgery.
AB  - Meniscal cartilage plays an essential role in the function and biomechanics of
      the knee joint. The meniscus functions in load bearing, load transmission, shock
      absorption, joint stability, joint lubrication, and joint congruity. Individuals
      today are increasingly more active in later decades of life. Although the
      incidence of meniscal pathology is difficult to estimate, this increased exposure
      to athletic activity increases the risk of injury to these structures. Hede and
      coworkers reported the mean annual incidence of meniscus tears as 9.0 in males
      and 4.2 in females per 10,000 inhabitants. Tears were found to be more common in
      the third, fourth, and fifth decades of life. It has become clearer in recent
      decades that meniscal excision leads to articular cartilage degeneration.
      Degenerative changes have been found to be directly proportional to the amount of
      meniscus removed. Therefore, it has been generally recognized that the amount of
      meniscal tissue removed should be minimized, repaired, or replaced. Whether a
      meniscal lesion is treated conservatively or surgically, the rehabilitation
      program will play an important role in the functional outcome. This article will
      discuss these programs and the various treatment strategies employed. 

PMID- 25390474
TI  - Circumferential lacquer cracks in a highly myopic patient.

PMID- 25390475
TI  - Chronic ocular ischemia associated with primary pulmonary hypertension.

PMID- 25390476
TI  - Full-thickness macular hole following intravitreal injection of triamcinolone
      acetonide in central retinal vein occlusion.

PMID- 25390477
TI  - Giant nodular posterior scleritis mimicking choroidal tumor.

PMID- 25390478
TI  - Choroidal perfusion delay and hyperpermeability in exudative retinal detachment
      induced by panretinal scatter photocoagulation.

PMID- 25390479
TI  - Development of retinal pigment epithelium alternation following single
      photodynamic therapy for age-related macular degeneration.

PMID- 25390480
TI  - Subretinal fibrosis mimicking chorioretinal anastomosis following photodynamic
      therapy.

PMID- 25390481
TI  - Retinopathy in adult amyopathic dermatomyositis.

PMID- 25390482
TI  - Short-term effects of intravitreal bevacizumab in type 2 idiopathic macular
      telangiectasia.

PMID- 25390483
TI  - Posterior scleral choristomas and trigeminal lipoma in the organoid nevus
      syndrome.

PMID- 25390484
TI  - Short wavelength perimetry (swap) in a case of multiple evanescent white dot
      syndrome (mewds).

PMID- 25390485
TI  - Diffuse retinal arterial occlusion, neovascularization, and vitreous hemorrhage
      as the presenting sign of sneddon syndrome: a 7.5-year angiographic follow-up.

PMID- 25390486
TI  - Optical coherence tomography in congenital hypertrophy of the retinal pigment
      epithelium.

PMID- 25390487
TI  - Bilateral exudative retinal detachments in tubulointerstitial nephritis and
      uveitis syndrome secondary to posterior scleritis.

PMID- 25390488
TI  - Improved fundus visualization during vitreous surgery using a combination of a
      prism contact lens and indirect ophthalmoscopy.

PMID- 25390489
TI  - Continuous scleral drainage in vitrectomy for bullous retinal detachment.

PMID- 25390490
TI  - Management of intrachoroidal silicone oil.

PMID- 25390491
TI  - Combined achromobacter (alcaligenes) piechaudii and mycobacterium chelonae
      infection on an extruding scleral buckle.

PMID- 25390492
TI  - Subretinal band: clinicopathologic correlation of a pseudoparasite.

PMID- 25390493
TI  - Presumed subretinal migration of platelets concentrate following macular hole
      surgery.

PMID- 25390494
TI  - Concentration-related response potentiometric titrations to study the interaction
      of small molecules with large biomolecules.
AB  - In the present paper, the utility of a special potentiometric titration approach
      for recognition and calculation of biomolecule/small-molecule interactions is
      reported. This approach is fast, sensitive, reproducible, and inexpensive in
      comparison to the other methods for the determination of the association constant
      values (Ka) and the interaction energies (DeltaG). The potentiometric titration
      measurement is based on the use of a classical polymeric membrane indicator
      electrode in a solution of the small-molecule ligand. The biomolecule is used as
      a titrant. The potential is measured versus a reference electrode and transformed
      into a concentration-related signal over the entire concentration interval, also
      at low concentrations, where the millivolt (y-axis) versus log canalyte (x-axis)
      potentiometric calibration curve is not linear. In the procedure, Ka is
      calculated for the interaction of cocaine with a cocaine binding aptamer and with
      an anticocaine antibody. To study the selectivity and cross-reactivity, other
      oligonucleotides and aptamers are tested, as well as other small ligand molecules
      such as tetrakis(4-chlorophenyl)borate, metergoline, lidocaine, and bromhexine.
      The calculated Ka compared favorably to the value reported in the literature
      using surface plasmon resonance. The potentiometric titration approach called
      "concentration-related response potentiometry" is used to study molecular
      interaction for seven macromolecular target molecules and four small-molecule
      ligands. 

PMID- 25390495
TI  - Optimising pharmacotherapy for secondary prevention of non-invasively managed
      acute coronary syndrome.
AB  - About half of all patients who experience an acute coronary syndrome (ACS) in
      Australia have their conditions managed non-invasively - that is, they do not
      undergo coronary angiography and revascularisation in hospital. ACS patients
      whose conditions are managed non-invasively may not receive the same level of
      evidence-based care as those who receive coronary revascularisation. This article
      reviews the optimal pharmacological management of ACS managed non-invasively.
      There is strong evidence to support the prescription of dual antiplatelet therapy
      (DAPT; aspirin with a P2Y12 inhibitor). DAPT should continue for 12 months after
      an ACS, then aspirin should be continued indefinitely. Anticoagulation with
      warfarin or a novel oral anticoagulant may be needed if atrial fibrillation
      occurs; the combination with DAPT increases the risk of bleeding. Unless
      contraindicated, high-intensity statin therapy should be prescribed for all post
      ACS patients irrespective of their cholesterol level. Non-statin lipid therapy
      has not been shown to improve outcomes. Use of beta-adrenergic blockers is
      recommended in most guidelines, but the clinical trials to support this
      recommendation were performed more than 30 years ago, and routine long-term use
      may not be relevant to modern treatment, except when there is cardiac failure or
      left ventricular dysfunction. Angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers are also widely recommended, but the evidence for
      benefit is stronger when there is left ventricular dysfunction. Calcium-channel
      blockers, nitrates, antiarrhythmic drugs, digoxin and diuretics do not improve
      outcomes in post-ACS patients. 

PMID- 25390496
TI  - Adherence to secondary prevention therapies in acute coronary syndrome.
AB  - Despite overwhelming evidence of the effectiveness of secondary prevention
      therapies, surveys indicate poor adherence to medical treatments and lifestyle
      recommendations after an acute coronary syndrome. The term adherence is preferred
      over compliance, as the former suggests a therapeutic alliance, whereas the
      latter reflects passive patient obedience. Poor adherence results from a complex
      interplay of multiple factors at patient, practitioner and system levels. Poor
      adherence among patients with stable coronary artery disease is associated with
      increased risk of cardiovascular admissions (10%-40%), coronary interventions
      (10%-30%) and cardiovascular mortality (50%-80%). Improving adherence is a
      complex process. A range of interventions that target modifiable factors
      influencing adherence have been explored, but there are no guidelines to guide
      the choice, and multidisciplinary efforts may be needed. Future research in the
      area should focus on comparative efficacy of interventions to enhance adherence. 

PMID- 25390497
TI  - Eight challenges faced by general practitioners caring for patients after an
      acute coronary syndrome.
AB  - The general practitioner is essential in the management of the patient who has
      recently been discharged from hospital following an acute coronary syndrome
      (ACS), particularly as duration of hospital stay is shorter than in previous
      decades. GPs caring for patients after an ACS face numerous challenges. Often,
      the first of these is insufficient or delayed documentation from the discharging
      hospital, although electronic discharge summaries are alleviating this problem.
      Post-ACS patients often have comorbidities, and GPs play a key role in managing
      these. Patients taking dual antiplatelet therapy who need surgery, and post-ACS
      patients with atrial fibrillation, require particular care from GPs. Patients
      will often approach their GP for advice on the safety of other drugs, such as
      smoking cessation medication, and phosphodiesterase type 5 inhibitors for
      erectile dysfunction. For patients complaining of persistent lethargy after an
      ACS, GPs must consider several differential diagnoses, including depression,
      hypotension, hypovolaemia, and side effects of beta-blockers. GPs play an
      important ongoing role in ensuring that target cholesterol levels are reached
      with statin therapy; this includes ensuring long-term adherence. They may also
      need to advise patients who want to stop statin therapy, usually due to perceived
      side effects. Many of these challenges can be met with improved and respectful
      communication between the hospital, the treating cardiologist and the GP. The
      patient needs to be closely involved in the decision-making process, particularly
      when balancing the risks of bleeding versus thrombosis. 

PMID- 25390498
TI  - Modern challenges in acute coronary syndrome.

PMID- 25390499
TI  - Optimising acute care and secondary prevention for patients with acute coronary
      syndrome.
AB  - Ascertaining a patient's risk of ischaemic complications after admission with an
      acute coronary syndrome is an important determinant of management. The treating
      clinician must determine whether and how urgently to send the patient for
      coronary angiography and whether to select more intensive antithrombotic
      therapies in the acute phase, and facilitate secondary prevention strategies.
      Risk stratification is infrequently applied and, as a consequence, undertreatment
      of higher-risk patients is common. Ensuring routine application of risk
      stratification across hospitals may improve treatment of patients who have the
      most to gain from evidence-based therapies. This requires embedding standard
      practices into complex clinical environments, and includes the routine
      implementation of treatment algorithms in a permissive environment with clinical
      champions and support from the hospital administration. The implementation of
      routine systems of care defining prehospital, interhospital and individual
      hospital practice is challenging, but essential to minimise deficits in care. 

PMID- 25390500
TI  - Management of acute coronary syndrome in special subgroups: female, older,
      diabetic and Indigenous patients.
AB  - While the evidence base for management of acute coronary syndrome (ACS) is
      extensive, some subgroups have been underrepresented or excluded from relevant
      clinical trials. These subgroups - such as women, older people, diabetic patients
      and Indigenous Australians - present clinical challenges for which there is
      limited evidence to guide optimal therapy. Women may have a different pattern of
      presentation, with potential for delays in diagnosis and worse outcomes in ST
      elevation myocardial infarction, but there is no evidence that treatments affect
      them differently from men. Older people suffer from a high-risk, low-treatment
      paradox. This may be due to under-appreciation of the benefits of treatments for
      older people, or to good clinical judgement in avoiding harm from worsening age
      related comorbidities. Patients with diabetes have a high risk of ACS and suffer
      worse outcomes. Moderate glycaemic control with close monitoring and avoidance of
      hypoglycaemia are recommended. Coronary artery bypass grafting is preferred to
      percutaneous coronary intervention for patients with diabetes and multivessel
      disease, although the latter is reasonable in single-vessel disease. Indigenous
      patients have a high prevalence of coronary disease, with more frequent coronary
      events at a young age, a heavy load of risk factors and poor outcomes after ACS.
      The complex sociocultural barriers to treatment are yet to be addressed
      adequately. 

PMID- 25390501
TI  - The transition from hospital to primary care for patients with acute coronary
      syndrome: insights from registry data.
AB  - Despite guidelines advocating routine engagement with proven secondary prevention
      strategies, current uptake and access remain suboptimal. Australian registries of
      acute coronary syndrome have predominantly focused on inpatient care and have
      highlighted under-referral to cardiac rehabilitation, gaps in medication
      prescription and limited commencement of lifestyle change before discharge from
      hospital. Opportunities to improve equity, access and uptake of secondary
      prevention include better transition between acute and primary care, systematic
      delivery of prevention in primary care, workforce strengthening and embracing new
      technologies. Adopting a structured framework for delivery of secondary
      prevention in primary care will enhance continuity of care and improve
      coordination of services after acute coronary syndrome. 

PMID- 25390503
TI  - An automated method for fibrin clot permeability assessment.
AB  - The fibrin clot permeability coefficient (Ks) is a useful measure of porosity of
      the fibrin network, which is determined by a number of genetic and environmental
      factors. Currently available methods to evaluate Ks are time-consuming, require
      constant supervision and provide only one parameter. We present an automated
      method in which drops are weighed individually, buffer is dosed by the pump and
      well defined clot washing is controlled by the software. The presence of a
      straight association between drop mass and their dripping time allows to shorten
      the measurement time twice. In 40 healthy individuals, Ks, the number of drops
      required to reach the plateau (DTP), the time to achieve the plateau (TTP) and
      the DTP/TTP ratio (DTR) were calculated. There was a positive association between
      Ks (r = 0.69, P < 0.0001) evaluated by using the manual [median of 4.17 (3.60
      5.18) .10-9 cm2) and the automated method [median of 4.35 (3.74-5.38) .10-9 cm2].
      The correlation was stronger (r = 0.85, P < 0.001) in clots with DTP of 7 or less
      (n = 12). DTP was associated with total homocysteine (tHcy) (r = 0.35, P < 0.05)
      and activated partial thromboplastin time (APTT) (r = -0.34, P < 0.05), TTP with
      Ks (r = -0.55, P < 0.01 for the manual method and r = -0.44, P < 0.01 for the
      automated method) and DTP (r = 0.75, P < 0.0001), and DTR with Ks (r = 0.70, P <
      0.0001 for the manual method and r = 0.76, P < 0.0001 for the automated method),
      fibrinogen (r = -0.58, P < 0.0001) and C-reactive protein (CRP) (r = -0.47, P <
      0.01). The automated method might be a suitable tool for research and clinical
      use and may offer more additional parameters describing fibrin clot structure.

PMID- 25390502
TI  - Anterior insula volume and guilt: neurobehavioral markers of recurrence after
      early childhood major depressive disorder.
AB  - IMPORTANCE: This is the first study to date to examine volumetric alterations in
      the anterior insula (AI) as a potential biomarker for the course of childhood
      major depressive disorder (MDD). OBJECTIVES: To examine whether children with a
      history of preschool-onset (PO) MDD show reduced AI volume, whether a specific
      symptom of PO MDD (pathological guilt) is related to AI volume reduction (given
      the known relationship between AI and guilt processing), and whether AI volumes
      predict subsequent likelihood of having an episode of MDD. DESIGN, SETTING, AND
      PARTICIPANTS: In a prospective longitudinal study, 306 children (age range, 3.00
      5.11 years) and caregivers completed DSM diagnostic assessments at 6 annual time
      points during 10 years as part of the Preschool Depression Study. Magnetic
      resonance imaging was completed on a subset of 145 school-age children (age
      range, 6.11-12.11 years). MAIN OUTCOMES AND MEASURES: Whole-brain-adjusted AI
      volume measured using magnetic resonance imaging at school age and children's
      diagnosis of MDD any time after their imaging. RESULTS: Compared with children
      without a history of PO MDD, school-age children previously diagnosed as having
      PO MDD had smaller left and right AI volumes (Wilks Lambda = 0.94, F2,124 = 3.37,
      P = .04, Cohen d = 0.23). However, the effect of PO MDD on reduced AI volumes was
      better explained by children's experience of pathological guilt during preschool
      (Lambda = 0.91, F2,120 = 6.17, P = .003, d = .30). When covarying for children's
      lifetime history of MDD episodes, their experience of pathological guilt during
      preschool, as well as their sex and age at the time of imaging, schoolchildren's
      right-side AI volume was a significant predictor of being diagnosed as having an
      MDD episode after imaging (odds ratio, 0.96; 95% CI, 0.01-0.75; P = .03).
      CONCLUSIONS AND RELEVANCE: These results provide evidence that structural
      abnormalities in AI volume are related to the neurobiology of depressive
      disorders starting in early childhood. The present findings are consistent with
      mounting research in adult MDD suggesting that insula function and structure may
      be a target biomarker for major depression.

PMID- 25390504
TI  - Association of selenoprotein S gene polymorphism with ischemic stroke in a
      Chinese case-control study.
AB  - Previous studies showed that selenoprotein S (SELS) was associated with a range
      of inflammatory markers, and its gene expression was influenced by a polymorphism
      in the promoter region. The genetic basis of the ischemic stroke has now been
      largely determined, so the aim of the study was to examine the role of SELS
      genetic variants in the ischemic stroke risk in a Chinese population. We
      conducted a case-control study with 239 ischemic stroke patients and 240
      controls. Two single-nucleotide polymorphisms (SNPs) in SELS genes were analyzed
      for association with the risk of ischemic stroke in the Chinese Han population.
      No evidence of ischemic stroke association was observed with the SNP rs34713741.
      Interestingly, the strongest evidence showed that SELS SNP rs4965814 was
      associated with ischemic stroke (P < 0.05). We found a significant association
      with increased ischemic stroke risk in women carrying the CC genotype of
      rs4965814 [hazard ratio: 2.43(1.03-5.75)]; a similar trend was also found in men
      carrying the TC genotype of rs4965814 [hazard ratio: 1.81(1.06-3.08)]. SNP
      rs4965814 of SELS may affect the susceptibility to ischemic stroke. Understanding
      the inflammatory mechanisms of ischemic stroke may give new therapeutic targets
      to pharmacologists. 

PMID- 25390505
TI  - How do we encounter rare factor deficiencies in children? Single-centre results
      from Turkey.
AB  - BACKGROUND: Rare factor deficiencies (RFDs) are autosomal recessively inherited
      coagulation factor deficiencies encountered at a frequency of between one in 500,
      000 and one in two million. MATERIALS AND METHODS: One hundred and ninety-two
      patients, diagnosed as having RFD, followed and treated in our clinic between
      1990 and 2013 were retrospectively evaluated in this study. RESULTS: From the 192
      patients, 142 had FVII, 15 had FX, 14 had FXI, 10 had fibrinogen, six had FV, two
      had FXIII, two had FV + FVIII and one had FII deficiency. One hundred and thirty
      of the cases were boys and 62 were girls. The age range was 2 weeks to 24 years
      and the ages at the admission were between 2 weeks and 16 years. The rate of
      consanguinity was 49.4%. Eighty-eight of our patients were asymptomatic (45.8%)
      and 104 were symptomatic (54.2%). Asymptomatic patients were diagnosed by family
      histories (39.8%), preoperative laboratory studies (54.6%) and operational
      bleeding (5.6%). Sixty-eight of our symptomatic patients displayed grade II
      (65.4%) and 36 displayed grade III bleeding symptoms (34.6%). First bleeding
      regions were skin (33%), nose (28%), central nervous system (CNS) (15.5%), oral
      cavity (10.5%), soft tissue (6%), joint (3%), urinary system (2%) and
      gastrointestinal system (GIS) (2%), respectively. The bleeding prevalence rates
      of our symptomatic patients are listed as epistaxis 62.5%, skin bleedings 53%,
      oral cavity bleeding 28.8%, haematomas 18.3%, CNS bleedings 17.3%, haemarthrosis
      14.4%, GIS bleedings 3.8%, menorrhagia 2.9%, haematuria 1.9%, bleeding because of
      operations 1.9% and iliopsoas bleedings 1.9%. CNS bleedings (41%) take the first
      place among the serious bleedings of our cases, followed by haemarthrosis
      (36.4%), GIS bleedings (18.1%) and iliopsoas bleedings (4.5%). Prophylaxy was
      applied to nine patients (five patients with FVII, two patients with fibrinogen
      and one each with FV and FX deficiency). CONCLUSIONS: The characteristics of
      clinical presentations, first bleeding attacks, bleeding prevalence and severe
      bleedings as well as prophylactic approaches are discussed in this article.

PMID- 25390506
TI  - Scaling the Feeding Mechanism of Captive Alligator mississippiensis from
      Hatchling to Juvenile.
AB  - Small changes in size can lead to potential performance consequences and may
      influence an organism's ability to utilize resources in its environment. As the
      American alligator (Alligator mississippiensis) transitions between neonate,
      juvenile and adult habitats (ontogenetic niche shifts), there are inevitably
      dynamic changes in their feeding performance. This study sought to investigate
      the scaling of the feeding mechanism and its performance from hatchling to
      juvenile size classes in A. mississippiensis. Feeding events were recorded during
      March 2011 at Rockefeller Wildlife Refuge (Grand Chenier, Louisiana). Thirty-six
      captive individuals were randomly sampled, ranging from 30.5 cm to 91.5 cm total
      length, and feeding events were recorded using a high speed camera at a rate of
      300 fps. Results indicated that many linear, angular and timing kinematic
      variables scale allometrically with cranium length; whereas maximum gape velocity
      and duration of feeding bout do not scale with cranium length and remain constant
      between these size classes. Although it has been shown that there is an isometric
      relationship between cranial elements and body size in A. mississippiensis, this
      relationship is not transferred to linear and timing variables of prey-capture
      events. These allometric relationships echo other investigations of scaling
      relationships such as bite-force production and terrestrial locomotion. 

PMID- 25390507
TI  - Efficient and highly enantioselective construction of trifluoromethylated
      quaternary stereogenic centers via high-pressure mediated organocatalytic
      conjugate addition of nitromethane to beta,beta-disubstituted enones.
AB  - A very effective high-pressure-induced acceleration of asymmetric organocatalytic
      conjugate addition of nitromethane to sterically congested beta,beta
      disubstituted beta-CF3 enones has been developed. A combination of pressure (8-10
      kbar) and noncovalent catalysis with low-loading of chiral tertiary amine
      thioureas (0.5-3 mol %) is shown to provide very efficient access to a wide range
      of gamma-nitroketones containing trifluoromethylated all-carbon quaternary
      stereogenic centers in the beta-position (80-97%, 92-98% ee). 

PMID- 25390508
TI  - Ruthenium hydrides containing the superhindered polydentate polyphosphine ligand
      P(CH2CH2P(t)Bu2)3.
AB  - The complex RuH2(N2)(P(2)P3(tBu)) (1) containing the extremely bulky PP3-type
      ligand P(2)P3(tBu) = P(CH2CH2P(t)Bu2)3 was synthesized by reduction of
      RuCl2(P(2)P3(tBu)) (2) with Na/NH3 under a N2 atmosphere. Like other complexes
      containing the P(2)P3(tBu) ligand, only three of the four donor phosphines are
      coordinated, and one of the phosphines remains as a dangling pendant phosphine.
      Reduction of RuCl2(P(2)P3(tBu)) (2) with a range of the more usual hydride
      reducing agents afforded the previously unknown ruthenium hydride complexes
      RuHCl(P(2)P3(tBu)) (3), RuH(BH4)(P(2)P3(tBu)) (6), RuH(AlH4)(P(2)P3(tBu)) (7),
      and the ruthenium(II) trihydride K[Ru(H)3(P(2)P3(tBu))] (8). The ruthenium
      tetrahydride containing a coordinated H2 ligand RuH2(H2)(P(2)P3(tBu)) (10) was
      synthesized by exchange of N2 in 1 by H2. Complexes 1, 3, 6, 7, and 8 were
      characterized by crystallography and multinuclear NMR spectroscopy. 

PMID- 25390509
TI  - Takayasu retinopathy presenting as amaurosis fugax in a young patient.
AB  - PURPOSE: The purpose of this article was to report a case of Stage 3 Takayasu
      retinopathy with marked venous staining. METHODS: Case report with funduscopic,
      fluorescein angiography, computed tomography angiography, and magnetic resonance
      imaging angiography correlations. RESULTS: A 25-year-old woman presented with
      Stage 3 Takayasu retinopathy with striking venous staining while maintaining
      visual acuity of 20/30 because of arterial collateralization to the internal
      carotid arteries. CONCLUSION: Patients with Takayasu arteritis should be
      evaluated promptly for Takayasu retinopathy even with good vision because
      stenosis of major vessels off the aorta is associated with worse visual
      prognosis.

PMID- 25390510
TI  - Acute macular neuroretinopathy: an atypical case.
AB  - PURPOSE: The purpose of this report is to describe extensive acute macular
      neuroretinopathy lesions with atypical features. METHODS: Retrospective case
      report. RESULTS: A patient developed acute macular neuroretinopathy in the
      setting of multiple previously described associations including a flu-like
      illness, sympathomimetic exposure, overdose of norepinephrine reuptake
      inhibitors, anemia, thrombocytopenia, and hypotensive shock. The fundus lesions
      superficially resembled retinal hemorrhages in color and fluorescein angiography
      pattern. The lesions could be detected on autofluorescence and infrared imaging.
      Optical coherence tomography revealed outer plexiform layer opacification and
      photoreceptor abnormalities. CONCLUSION: This case suggests a compounding effect
      of factors associated with acute macular neuroretinopathy, possible exacerbating
      insults and outer plexiform layer abnormalities that may correlate with the
      temporal course of this condition.

PMID- 25390511
TI  - Multifocal retinal astrocytic hamartomas: a case series and review of the
      literature.
AB  - PURPOSE: Retinal astrocytic hamartoma is a benign glial tumor found in the nerve
      fiber layer, and it is most commonly reported as a solitary lesion. Multiple or
      bilateral lesions may be indicative of systemic disease, such as tuberous
      sclerosis complex or neurofibromatosis 1. We present three unique cases of
      multifocal and bilateral retinal astrocytic hamartomas in patients with suspected
      tuberous sclerosis complex. The typical features, diagnosis, management, and
      systemic implications of these retinal lesions are discussed. METHODS:
      Consecutive case series at a university-based ophthalmology clinic. RESULTS: The
      age of the patients ranged from 9 years to 27 years. The patients came from
      different ethnic backgrounds and had no known family history of tuberous
      sclerosis complex or neurofibromatosis. Two of the three patients had asthma,
      along with brain and kidney tumors. Two of the three patients had a seizure
      disorder, and one of the three patients had mental retardation. Only one patient
      presented with an ocular complaint of decreased vision, as a result of a presumed
      unrelated process. All patients had bilateral and multifocal astrocytic
      hamartomas. CONCLUSION: Multifocal retinal astrocytic hamartomas are unique and
      can be the first manifestation of a systemic disease such as tuberous sclerosis
      complex or neurofibromatosis 1. Prompt referral for imaging and workup with the
      appropriate medical subspecialty can help prevent or delay the morbidity related
      to these systemic conditions.

PMID- 25390512
TI  - Subretinal deposits, paramacular atrophy and pigmentary retinopathy in
      mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes.
AB  - PURPOSE: To report a case of subretinal deposits, paramacular atrophy, and
      pigmentary retinopathy associated with mitochondrial encephalopathy, lactic
      acidosis, and stroke-like episodes. METHODS: Retrospective review of medical
      records. RESULTS: A 45-year-old white woman presented with progressive
      deterioration of vision and dark adaptation over several years. She had a
      background of an undiagnosed neurodegenerative disorder, including sensorineural
      hearing loss, cognitive disturbance, and peripheral neuropathy. On examination,
      subretinal deposits were visible along the superotemporal arcades. A diagnosis of
      mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes was
      confirmed by genetic testing (A3243G gene mutation). Four years later, she had
      developed paramacular atrophy and pigmentary retinopathy. CONCLUSION:
      Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes may be
      associated with paramacular atrophy and pigmentary retinopathy. Autofluorescent
      changes may precede these signs and can help distinguish this condition from
      Stargardt disease-fundus flavimaculatus. As far as we are aware, this is the
      first report of fundus autofluorescence imaging and optical coherence tomography
      in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes
      associated retinopathy. Subretinal deposit may be an early sign.

PMID- 25390513
TI  - The seasick choroid: a finding on enhanced depth imaging spectral-domain optical
      coherence tomography of choroidal lymphoma.
AB  - PURPOSE: To describe previously unreported imaging features of choroidal lymphoma
      using enhanced depth imaging optical coherence tomography (OCT). METHODS:
      Enhanced depth imaging OCT was performed before and after the therapy. RESULTS: A
      32-year-old white man with a 4-month history of blurred vision in the right eye
      was found to have a macular fold. There was no visible intraocular tumor. There
      were no signs of anterior segment inflammation, vascular abnormalities, or
      infiltrative disease. Visual acuity was 20/150 in the right eye and 20/20 in the
      left eye. Enhanced depth imaging OCT demonstrated a macular retinal fold and
      marked thickening of the choroid with striking choroidal surface undulation and
      folds imparting an appearance similar to a "sea storm" (seasick appearance). Deep
      choroidal structures could not be visualized, and the sclerochoroidal interface
      could not be identified. Overlying subretinal fluid and intraretinal fluid was
      noted. Ultrasonography demonstrated diffuse, relatively smooth thickening of the
      choroid (4.0-mm thickness) with minor extraocular hypoechoic area. Based on these
      findings, choroidal lymphoid proliferation was suspected, and fine-needle
      aspiration biopsy confirmed B-cell lymphoma. Results of systemic evaluation were
      unremarkable. After external beam radiotherapy with dose of 40 Gy, visual acuity
      returned promptly to 20/40 and the lymphoid infiltration resolved with flattening
      of the macular fold and resolution of subretinal and intraretinal fluids. The
      enhanced depth imaging OCT returned to a more normal appearance with the
      resolution of the retinal fold and reduction of the choroidal mass with retinal
      pigment epithelial-choroidal surface features to a "calm sea" appearance.
      CONCLUSION: Enhanced depth imaging OCT is a useful tool for subclinical
      monitoring of choroidal infiltration from lymphoma before and after therapy.

PMID- 25390514
TI  - Single-agent, minimal dose, minimal exposure intraarterial chemotherapy for
      retinoblastoma in a 4-month-old infant.
AB  - PURPOSE: To document minimal dose and minimal exposure of chemotherapy for
      unilateral retinoblastoma. METHODS: A 4-month-old infant developed leukocoria in
      the right eye and was found to have unilateral sporadic retinoblastoma. RESULTS:
      The right eye was classified as Group D retinoblastoma, with a single large
      tumor, moderate subretinal seeding, and total retinal detachment. The
      retinoblastoma measured 20 mm in basal dimension and 13 mm in ultrasonographic
      thickness. Options of enucleation, intravenous chemotherapy, and intraarterial
      chemotherapy were offered, but the latter was chosen because of anticipated,
      rapid, and more complete response with intraarterial rather than intravenous
      chemotherapy. After using low dose (3 mg) of single-agent melphalan delivered
      over 30 minutes into the ostium of the ophthalmic artery of the 4-month-old
      infant, a complete response with Type 1 regression (complete calcification) of
      the mass and resolution of all subretinal fluid was found. A second similar dose
      was delivered to ensure remission of all seeds and tumor with stable findings.
      Further chemotherapy was stopped. On 6 months of follow-up, the child displayed
      complete tumor control with 2 cycles of lowest dose (3 mg) intraarterial
      melphalan. There were no complications. CONCLUSION: In infants younger than 6
      months, low dose of only 3-mg single-agent melphalan could be sufficient to
      control retinoblastoma with minimal exposure.

PMID- 25390515
TI  - Simultaneous fzd4 and lrp5 mutation in autosomal dominant familial exudative
      vitreoretinopathy.
AB  - PURPOSE: The purpose of this study was to report simultaneous mutations of FZD4
      and LRP5 genes associated with autosomal dominant familial exudative
      vitreoretinopathy in members of one family. METHODS: Case report. RESULTS: A 16
      month-old white boy with a 6-month history of leukocoria was referred for
      possible retinoblastoma. On examination, the left eye displayed extensive white
      vitreoretinal fibrosis filling the entire vitreous cavity up to the lens and with
      additional dystrophic calcification and iris neovascularization. The right eye
      showed temporal peripheral fibrovascular ridge. Fluorescein angiography showed
      360 degrees  of peripheral nonperfusion with leakage from the fibrovascular ridge
      of the right eye and diffuse leakage from the massive vitreoretinal fibrosis and
      iris neovascularization of the left eye, consistent with familial exudative
      vitreoretinopathy. Laser photocoagulation of the avascular areas of the right eye
      was performed with disease stabilization. Clinical examination and genetic
      testing of the family members demonstrated that the proband and a male sibling
      had similar clinical findings and simultaneous mutations in the FZD4 and LRP5
      genes. Both affected patients had normal bone mineral dual-energy X-ray
      absorptiometry. CONCLUSION: Familial exudative vitreoretinopathy is a retinal
      vascular disorder usually caused by a single mutation. Rarely, multiple
      simultaneous mutations can occur and, in this case, result in classic ophthalmic
      phenotypic and known risk for bone disorders.

PMID- 25390516
TI  - Cytomegalovirus retinitis in dyskeratosis congenita.
AB  - PURPOSE: The purpose of this study was to report a case of cytomegalovirus
      retinitis in the setting of dyskeratosis congenita. METHODS: Case report and
      literature review. RESULTS: A 23-year-old woman who had peripheral occlusive
      retinal vasculopathy and neovascularization as a result of pancytopenia caused by
      bone marrow failure also developed cytomegalovirus retinitis. She had been
      diagnosed with dyskeratosis congenita, which had caused the bone marrow failure
      and pancytopenia. CONCLUSION: Dyskeratosis congenita is a multisystem disorder
      that causes bone marrow failure. It can have retinal manifestations in the form
      of peripheral proliferative retinopathy and retinitis.

PMID- 25390517
TI  - PARASITE IN A YOUNG GIRL FROM VIETNAM PRESENTING AS A GOLDEN FOVEAL LESION:
      Submacular Fly Larva or Nematode?
AB  - PURPOSE: To report a case of likely subretinal foveal parasite, either
      ophthalmomyiasis from botfly infestation, Angiostrongylus or Gnathostoma.
      METHODS: Observational case report of a patient with decreased vision in the left
      eye since age 4, with examination showing a golden subretinal foveal lesion. She
      was monitored up to age 24. RESULTS: A young woman originally from Vietnam
      presented at age 11 with vision loss in the left eye since age 4 after a severe
      febrile illness. Fundus examination revealed a subretinal golden foveal lesion.
      History, angiography, and spectral domain optical coherence tomography revealed
      the possibility of parasitic infestation with an entrance site. CONCLUSION: In
      patients with focal lesions of unknown etiology, careful history, exam,
      angiography and OCT may indicate a parasitic organism and the entrance site.

PMID- 25390518
TI  - The use of vascular endothelial growth factor inhibitor for choroidal
      neovascularization complicating posterior uveitis in eyes with fluocinolone
      acetonide implants.
AB  - PURPOSE: To present a series of eyes with multifocal choroiditis and panuveitis
      (MFC) treated with fluocinolone acetonide intravitreal implants. All eyes
      developed recurrent choroidal neovascularization (CNV) and were treated with
      intravitreal bevacizumab or ranibizumab. METHODS: Retrospective chart review.
      Data collected included demographics, details of previous immunosuppressive
      therapy, preinjection Snellen visual acuity, and central macular thickness
      measured by optical coherence tomography, total injections administered, and
      postinjection central macular thickness and visual acuity. Patients were followed
      up for a minimum of 25 months from the first fluocinolone acetonide implant.
      Duration from implantation to first injection and complications, including
      development of cataracts, glaucoma, and recurrent inflammation, were followed.
      PATIENTS: Three patients treated for MFC at the Casey Eye Institute, a tertiary
      care referral center at Oregon Health & Science University, from 2005-2008 were
      studied. All three received fluocinolone acetonide implants and later underwent
      intravitreal anti-vascular endothelial growth factor (VEGF) therapy for CNV.
      RESULTS: Preinjection visual acuity in 3 patients was 1.2, 0.54, and 0.48
      logarithm of minimal angle of resolution (mean 0.74). Postinjection visual acuity
      in 3 patients was 1.0, 0.40, and 0.0 logarithm of minimal angle of resolution
      (mean 0.47). Preinjection central macular thicknesses were 855 MUm, 215 MUm, and
      276 MUm (mean 449 MUm). Postinjection central macular thicknesses were 220 MUm,
      190 MUm, and 223 MUm (mean 211 MUm). Anti-VEGF injections did not reactivate
      inflammation. Advancing cataracts contributed to worsening visual acuity
      postinjection. The total number of anti-VEGF injections until resolution of
      intraretinal and subretinal fluid associated with CNV was 6 injections for case
      1, 1 for case 2, and 8 for case 3 (mean 5, range 1-8). CONCLUSION: Intravitreal
      anti-VEGF therapy was successful in treating recurrent CNV in MFC patients with
      well-controlled inflammation after insertion of fluocinolone acetonide implants.
      Anti-VEGF therapy should be considered in treating active CNV in eyes with MFC
      and quiescent inflammatory disease.

PMID- 25390519
TI  - Nonparaneoplastic autoimmune retinopathy presenting with peripheral retinal
      vasoocclusion: case report.
AB  - PURPOSE: To report a case of nonparaneoplastic autoimmune retinopathy presenting
      with severe peripheral retinal vasoocclusion. METHODS: Interventional case
      report. CASE REPORT: A 44-year-old woman complained of blurred vision and
      photopsia in both eyes. She has no history of cancer or autoimmune disease. Best
      corrected visual acuity was 20/40 in the left eye and 20/30 in the right eye.
      Constriction of the visual field sparing central vision was found. Fluorescein
      angiography revealed severe peripheral retinal vasoocclusion, panretinal
      degeneration, and cystoid macular edema. Optical coherence tomography
      demonstrated intraretinal fluid. Electroretinography showed decreased amplitude
      of a- and b-waves in both scotopic and photopic tests. The implicit time was
      generally within normal limits. The amplitude of flicker response was also
      diminished. Multifocal electroretinography showed declined signal all over the
      macular region. Systemic workup including whole body positron emission
      tomography/computed tomography for cancer screening showed negative results. Only
      antirecoverin antibody was positive. Under the impression of nonparaneoplastic
      autoimmune retinopathy, systemic and local immunosuppressive therapy was given
      and showed improvement. CONCLUSION: Nonparaneoplastic autoimmune retinopathies
      are uncommon retinal degenerations with visual loss associated with unique
      clinical symptoms and findings and with serum antiretinal autoantibodies. Severe
      peripheral retinal vasoocclusion was not reported. Early detection and timely
      treatment with immunosuppression could result in clinical improvement.

PMID- 25390520
TI  - All-trans retinoic Acid differentiation syndrome chorioretinopathy: a case of
      multifocal serous neurosensory detachments in a patient with acute promyelocytic
      leukemia treated with all-trans retinoic Acid.
AB  - PURPOSE: The purpose of this study was to report a case of multifocal serous
      neurosensory retinal detachments associated with systemic differentiation
      syndrome (DS) (formerly known as all-trans retinoic acid [ATRA] syndrome) in a
      patient with acute promyelocytic leukemia. METHODS: In this observational case
      report, we identify a case of DS because of ATRA induction therapy with
      associated multiple focal serous neurosensory retinal detachments in a 39-year
      old man with acute promyelocytic leukemia. RESULTS: While suffering from a
      rebound episode of DS secondary to ATRA therapy, the patient experienced
      deterioration of his vision bilaterally. Within 8 days of discontinuing ATRA and
      the initiation of dexamethasone, the patient's systemic status and ocular
      findings resolved completely. Optical coherence tomography and fluorescein
      angiography confirmed the resolution of the subretinal fluid. CONCLUSION: Given
      the time of onset of the patient's visual symptoms with associated
      chorioretinopathy, his concurrent systemic manifestations of DS, along with his
      concurrent systemic, and ocular response to treatment, we speculate that this is
      the first reported occurrence of ATRA-associated chorioretinopathy in a patient
      with ATRA DS.

PMID- 25390521
TI  - Intraoperative breakage of a disposable 23-gauge trocar tip.
AB  - PURPOSE: To report breakage of the tip of a 23-gauge trocar system during pars
      plana vitrectomy. METHODS: Retrospective single case report. RESULTS: A 56-year
      old man was undergoing pars plana vitrectomy for vitreous hemorrhage using a 23
      gauge 1-step trocar/cannula entry system. After placement of the first cannula
      and upon withdrawing the trocar from the sclera, we noted that the tip had
      broken. We switched to another brand and completed the surgery without
      complication. Inspection of the fundus and plain radiography showed no
      intraocular foreign body, and the patient had an uncomplicated recovery.
      CONCLUSION: Vitreoretinal surgeons should be aware of the possibility of
      intraoperative breakage of the 23-gauge trocar tip after creation of the scleral
      tunnel.

PMID- 25390522
TI  - Choroidal infarction after photodynamic therapy combined with bevacizumab and
      triamcinolone reversed by tissue plasminogen activator: case report.
AB  - PURPOSE: To present a case of choroidal infarction after combined therapy of
      photodynamic therapy, intravitreal bevacizumab, and sub-Tenon triamcinolone
      injection salvaged by tissue plasminogen activator administration. METHODS:
      Interventional case report. RESULTS: Combined therapy of full-fluence
      photodynamic therapy, intravitreal bevacizumab, and sub-Tenon triamcinolone
      injection was given on the same day to treat neovascular age-related macular
      degeneration in an 82-year-old patient. Subsequent acute visual loss and marked
      macular edema as a result of choroidal infarction were noted. Intravitreal and
      sub-Tenon administration of tissue plasminogen activator were performed 9 days
      later to salvage the choroidal infarction, and visual improvement was noted.
      Fundoscopy and optical coherent tomography showed almost complete resolution of
      macular edema. Indocyanine green angiography revealed reperfusion of the
      choroidal vessels. CONCLUSION: Choroidal infarction may happen after combined
      therapy. Tissue plasminogen activator administration may reverse the infarction
      and help visual recovery.

PMID- 25390523
TI  - Prospective three-dimensional analysis of structure and function in vitreomacular
      adhesion cured by pharmacologic vitreolysis.
AB  - PURPOSE: To prospectively characterize macular structure and function as assessed
      by combined three-dimensional spectral-domain optical coherence tomography and
      scanning laser ophthalmoscopy and 3D computer-automated threshold Amsler grid,
      respectively, in a patient undergoing pharmacologic vitreolysis for vitreomacular
      adhesion with tractional cysts. METHODS: Combined 3D optical coherence tomography
      and scanning laser ophthalmoscopy measured macular volume and 3D computer
      automated threshold Amsler grid quantified central visual field function by
      determining the absolute percent magnitude lost (cumulative value of total visual
      field loss over all tested levels) before and for a period of 6 months after
      pharmacologic vitreolysis for vitreomacular adhesion with a single intravitreal
      injection of microplasmin (125 MUg; ThromboGenics). RESULTS: Ocriplasmin
      pharmacologic vitreolysis released vitreomacular adhesion by 2 weeks and
      decreased macular volume from 0.32 MUL to 0.15 MUL by 1 year after injection.
      There was a concomitant 4-fold improvement in visual function as measured by 3D
      computer-automated threshold Amsler grid (percent of central visual field lost)
      and Snellen visual acuity improved from 20/200 to 20/40. CONCLUSION: For
      assessing macular function improvement in conjunction with structural
      reintegration after pharmacologic vitreolysis for vitreomacular adhesion, 3D
      computer-automated threshold Amsler grid is a useful tool. Both 3D measurements
      quantitatively characterized the resolution of this patient's vitreomacular
      adhesion, suggesting that this is a useful approach to quantifying macular
      structure and function as indices of the severity of disease and the response to
      therapy.

PMID- 25390524
TI  - Bilateral macular serous retinal detachment revealing acute myeloblastic
      leukemia.
AB  - PURPOSE: To report a case of bilateral serous retinal detachment revealing acute
      myeloblastic leukemia. METHODS: A 31-year-old man presenting with decreased
      vision in both eyes, 20/50 in the right eye and 20/32 in the left eye, was
      submitted to a complete ophthalmologic and systemic evaluation. RESULTS: Fundus
      biomicroscopy, fluorescein and indocyanine green angiography, and spectral domain
      optical coherence tomography showed bilateral serous retinal detachment and signs
      of choroidal ischemia. Enhanced depth imaging spectral domain optical coherence
      tomography allowed a precise examination of the choroid, by showing an overall
      thickening of the choroid (749 MUm in the right eye and 728 MUm in the left eye)
      and disappearance of the normal hyporeflective visualization of the choroidal
      vessels. On systemic investigation, the patient was diagnosed with acute
      myeloblastic leukemia. After systemic chemotherapy, visual acuity improved to
      20/20 in both eyes, with resolution of the bilateral serous retinal detachment
      and choroidal changes. CONCLUSION: Bilateral serous retinal detachment may be a
      presenting sign of acute myeloblastic leukemia. Examination of the choroid using
      enhanced depth imaging spectral domain optical coherence tomography may suggest
      the etiology and contribute to early diagnosis and treatment.

PMID- 25390525
TI  - Retinal surgery-induced trigeminal neuralgia.
AB  - PURPOSE: To report a case of trigeminal neuralgia after retinal surgery in a 72
      year-old man. METHODS: Case report. RESULTS: A 72-year-old man developed severe
      postoperative pain after undergoing vitrectomy and endolaser therapy. The pain
      responded to neuroleptic medications once a diagnosis of trigeminal neuralgia was
      made. CONCLUSION: The authors report a case of trigeminal neuralgia developed
      after vitreoretinal surgery. Clinicians should consider trigeminal neuralgia in
      the differential diagnosis of atypical pain after retinal surgery.

PMID- 25390526
TI  - Extensive choroidal infiltrates in choroidal biopsy proven ocular sarcoidosis.
AB  - PURPOSE: To report a rare manifestation of ocular sarcoidosis. METHODS: Case
      report. RESULTS: A 50-year-old man was misdiagnosed and treated as acute retinal
      necrosis and was referred to our clinic. Fundus examination revealed bilateral,
      extensive, confluent, subretinal yellowish white infiltrates throughout the
      fundus. Choroidal biopsy was performed and revealed noncaseating granuloma.
      CONCLUSION: This case presents a rare manifestation of ocular sarcoidosis as
      extensive confluent choroidal infiltrates throughout the fundus. The lack of the
      evidence for systemic sarcoidosis and unusual ocular presentation necessitate
      choroidal biopsy to confirm the diagnosis.

PMID- 25390527
TI  - Atypical sorsby fundus dystrophy with a novel tyr159cys timp-3 mutation.
AB  - PURPOSE: The purpose of this study was to report a patient with an atypical
      presentation of Sorsby fundus dystrophy. METHODS: Retrospective chart review.
      RESULTS: A 38-year-old man with a family history of Sorsby fundus dystrophy
      presented for ophthalmic examination. The patient had unilateral disease with an
      atypical appearance mimicking a pattern dystrophy. Molecular analysis of the TIMP
      3 gene identified a Tyr159Cys mutation. He developed choroidal
      neovascularization, which was successfully treated with photodynamic therapy
      followed by intravitreal bevacizumab. CONCLUSION: Sorsby fundus dystrophy
      associated with a Tyr159Cys TIMP-3 point mutation may have a variable
      presentation. Intravitreal bevacizumab is useful in managing choroidal
      neovascularization associated with this condition.

PMID- 25390528
TI  - Rapidly enlarging choroidal melanoma: perioperative treatment implications.
AB  - PURPOSE: The purpose of this study was to describe a case of a rapidly enlarging
      choroidal melanoma that necessitated perioperative adjustment in treatment.
      METHODS: Observational case report. RESULTS: A 48-year-old white woman presented
      with decreased vision and floaters and was found to have a choroidal melanoma in
      her left eye. After discussion of risks and benefits of treatment, the patient
      elected radioactive plaque insertion. Intraoperative examination revealed that
      the choroidal melanoma had increased in height precluding plaque treatment.
      CONCLUSION: This case highlights the importance of intraocular examination and an
      informed consent that provides contingency therapies at the time of surgery.

PMID- 25390529
TI  - Valsalva retinopathy developing during Japanese cheerleading training
      ("ouendan").
AB  - PURPOSE: Valsalva hemorrhagic retinopathy is characterized by retinal hemorrhages
      that develop after a Valsalva maneuver that consists of a forcible exhalation
      against a closed glottis, thereby creating a sudden increase in the intrathoracic
      or intraabdominal pressure. We present a patient who developed retinal and
      vitreous hemorrhages with multiple retinal nonperfused areas after extreme
      physical training with shouting on a mountainous area. This exercise was part of
      his training as a member of a Japanese traditional cheerleading team. METHOD:
      Case presentation. RESULTS: A 19-year-old man developed an acute decrease in the
      vision to 0.3 in his left eye after running on hilly roads at approximately 800 m
      while shouting fight songs for several hours. Ophthalmoscopy showed a fresh
      vitreous hemorrhage that covered the entire macula and was connected to the optic
      disk in the left eye. The vitreous hemorrhage spontaneously resolved and an
      intraretinal hemorrhage and nonperfused area emerged. His visual acuity returned
      to 1.2. CONCLUSION: Prolonged, strenuous physical exertion with shouting during
      training exercises can lead to Valsalva hemorrhagic retinopathy. Several other
      factors, such as hot weather, altitude, and dehydration, may have played an
      additive role in increasing the venous pressure and hypoxia in the retinal
      vessels, which then caused the retinopathy.

PMID- 25390530
TI  - Optical coherence tomography findings in optic nerve pit maculopathy after
      vitrectomy.
AB  - PURPOSE: The purpose of this study was to present a case of optic nerve pit
      maculopathy and reappraise the previous concepts regarding the pathways of the
      fluid and the development. METHODS: A 24-year-old man had an optic nerve pit
      maculopathy. The visual acuity was 20/50 in the affected eye. Optical coherence
      tomography showed a multilayered separation of the neurosensory retina, serous
      retinal detachment, and the optic nerve pit with no membrane on the optic nerve.
      After 2 months of observations, surgery was performed. RESULTS: Surgery included
      vitrectomy, the separation of the posterior hyaloid, the internal limiting
      membrane peeling, and gas tamponade. No laser was performed. The vision improved
      to 20/20, and optical coherence tomography demonstrated that the inner retinal
      layer separation was resolved except for the ganglion cell layer connected to the
      optic nerve pit, and subretinal fluid was increased 1 month after surgery.
      Eventually, the retinal layer separation and the subretinal fluid were resolved
      completely. CONCLUSIONS: Vitrectomy with internal limiting membrane peeling and
      gas tamponade without any additional laser photocoagulation seems to be
      sufficient for the treatment. Our observations suggest that the fluid can move
      directly from the optic pit into multiple layers, and fluid emanating from the
      optic nerve pit still extended even after surgery.

PMID- 25390531
TI  - Massive exudative retinal detachment after photodynamic therapy for peripheral
      retinal capillary hemangioma.
AB  - PURPOSE: To report a case requiring emergency surgical intervention to treat a
      progressive massive retinal detachment after photodynamic therapy for a
      peripheral retinal capillary hemangioma associated with von Hippel-Lindau
      disease. METHODS: A 38-year-old woman with von Hippel-Lindau disease had a
      peripheral retinal capillary hemangioma in the left eye. At the initial visit,
      the best-corrected visual acuity was 20/250 in the left eye. Photodynamic therapy
      was applied to treat the hemangioma. After 1 day, a massive retinal detachment
      and vitreous hemorrhage occurred. Three days after photodynamic therapy,
      vitrectomy was performed to treat the retinal detachment, which progressed with
      visual deterioration to hand motions. RESULTS: A diagnosis of exudative retinal
      detachment was made because no retinal breaks were identified. The retina was
      reattached with external drainage and gas tamponade. One month postoperatively,
      the best-corrected visual acuity recovered to 20/100 in the left eye, and the
      vascular activity of the hemangioma stabilized. CONCLUSION: Photodynamic therapy
      monotherapy to treat retinal capillary hemangioma might result in a massive
      exudative retinal detachment requiring surgery.

PMID- 25390532
TI  - Choroiditis and choroidal neovascularization in acute disseminated
      encephalomyelitis.
AB  - PURPOSE: To present a case with bilateral choroidal neovascularization (CNV)
      secondary to acute disseminated encephalomyelitis-associated choroiditis
      requiring immunomodulatory therapy for prevention of recurrence. METHODS: The
      clinical course of a patient diagnosed with acute disseminated encephalomyelitis,
      who developed bilateral choroiditis at the time of his neurologic diagnosis and
      bilateral CNV 6 years later, is reviewed. PATIENT: A 57-year-old man developed
      CNV in both eyes, 6 years after the initial diagnosis of acute disseminated
      encephalomyelitis-associated choroiditis. The patient was initially treated
      successfully with intravitreal bevacizumab injections and oral prednisone, but
      CNV recurred with steroid tapering. Mycophenolate mofetil was initiated as
      steroid-sparing immunomodulatory therapy. RESULTS: There was no CNV recurrence
      for 1.5 years without the need for additional antiangiogenic therapy. CONCLUSION:
      To our best knowledge, this is the first report of choroiditis and secondary CNV
      associated with acute disseminated encephalomyelitis. In cases of recurrent CNV
      associated with choroiditis, systemic therapy should be strongly considered in
      conjunction with antiangiogenic therapy. The recurrence of CNV with tapering of
      oral steroids and the remission of CNV with steroid-sparing immunomodulatory
      therapy support the role of ongoing inflammation in the pathogenesis.

PMID- 25390533
TI  - Macular hole overlying pigment epithelial detachment after intravitreal injection
      with ranibizumab.
AB  - PURPOSE: To describe a previously unrecognized complication of intravitreal
      injection in a patient with exudative macular degeneration and vitreomacular
      adhesion. METHODS: Case report of a 69-year-old woman. RESULTS: One month after
      intravitreal injection with ranibizumab for exudative macular degeneration, our
      patient developed a full-thickness macular hole with visual acuity of 20/100.
      After pars plana vitrectomy with membrane peeling and fluid-gas exchange, the
      macular hole was closed and the visual acuity improved to 20/60. CONCLUSIONS:
      Macular hole formation after intravitreal injection with ranibizumab is a
      potential complication that should be considered before treatment, especially in
      those patients with large subfoveal pigment epithelial detachments and
      vitreomacular adhesion. Although successful closure may be attained after pars
      plana vitrectomy, this potential morbidity should be considered when treating
      these patients. In addition to the already well-described tractional forces of
      the vitreous overlying the fovea, and the potential contractile nature of a
      choroidal neovascular complex in response to ranibizumab, a posterior pushing or
      stretching mechanism of a large pigment epithelial detachment may also contribute
      to macular hole formation.

PMID- 25390534
TI  - Photocoagulation therapy of leaking archer's type 2 retinal arteriovenous
      communication.
AB  - PURPOSE: Type 2 retinal arteriovenous communication is characterized by direct
      arteriovenous communication without an intervening arteriolar or capillary
      segment. It may be complicated by extravascular exudation. The successful results
      of low-intensity argon laser photocoagulation in two cases are reported. METHODS:
      Case report of two patients. RESULTS: Both cases were associated with a serous
      macular detachment, showing evidence of vascular leakage. Argon laser
      photocoagulation was performed. Visual improvement was observed in both cases,
      with disappearance of vascular leakage. CONCLUSION: Type 2 arteriovenous
      communications lead to increased arterial flow through a low-resistance vein. The
      resulting high intraluminal pressure may explain the observed vascular ectasia
      and consequent fluid leakage. Spontaneous regression may occur. Nevertheless,
      direct argon laser photocoagulation may be considered a therapeutic option and
      lead to visual improvement.

PMID- 25390535
TI  - Sequential optical coherence tomography images of retinal necrosis in acute
      ocular toxoplasmosis.
AB  - PURPOSE: To describe the features of sequential spectral-domain optical coherence
      tomography (OCT) images in an eye with acute primary toxoplasmosis. METHODS: Case
      report of an individual diagnosed with acute primary toxoplasmic
      retinochoroiditis. Initial and follow-up spectral-domain OCT findings are
      described. RESULTS: This patient developed retinitis as a result of an acute
      infection consistent with Toxoplasma gondii suggested by toxoplasma-specific IgM
      serology and the response to therapy. The retinitis appeared initially as a
      hyperreflective region on spectral-domain OCT. An intraretinal cyst consistent
      with T. gondii parasitic infection was identified. Subsequent OCT images
      demonstrated progression to full-thickness retinal necrosis with the development
      of cystic spaces in the retina. CONCLUSION: Optical coherence tomography may be
      useful in characterizing the features, extent, and location of retinitis caused
      by T. gondii. Specific OCT features may indicate whether the infection is acute
      phase or becoming quiescent.

PMID- 25390536
TI  - Retinal detachment in a patient with leber congenital amaurosis.
AB  - PURPOSE: To report the unique presentation of a patient with Leber congenital
      amaurosis who developed a tractional retinal detachment involving the macula and
      underwent successful pars plana vitrectomy surgery. METHODS: Retrospective
      interventional case report. Chart review. RESULTS: A 54-year-old white woman,
      with molecularly confirmed CEP290-associated Leber congenital amaurosis, who
      initially presented with Snellen visual acuity of 20/200 in the right eye and
      20/125 in the left eye and constricted visual fields. The maculae were flat, the
      vessels were attenuated, and the periphery was flat with diffuse atrophic changes
      and bone spicule-like pigmentation in both eyes. Follow-up examination, 3 years
      later, demonstrated a temporal tractional retinal detachment in the left eye,
      which involved the macula; however, the vision was stable. She presented 4 months
      later, and her vision declined to light perception in the left eye and the
      traction retinal detachment now involved the entire macula. A pars plana
      vitrectomy was performed, and 8 months later, the visual acuity improved to
      20/300 in the left eye and the periphery was attached 360 degrees  with extensive
      bone spicule-like pigmentation and laser scars. CONCLUSION: Leber congenital
      amaurosis is a rare inherited retinal disease that can be complicated by
      tractional retinal detachment. Vitrectomy surgery can be used successfully to
      repair retinal detachments in this patient population. The patient had subsequent
      improvement in visual acuity and anatomical reattachment.

PMID- 25390537
TI  - Embyronal carcinoma of testis metastatic to ciliary body presenting as
      spontaneous hyphema and painful secondary glaucoma.
AB  - PURPOSE: To report a rare presentation of metastatic testicular cancer to the
      uvea. METHODS: Observational case report. RESULTS: A 24-year-old man without
      known systemic illness presented with acute total loss of vision and severe pain
      in his left eye and associated nausea, anorexia, and dehydration. He was found to
      have a total hyphema, high intraocular pressure, and a ciliary body mass (by
      computed tomography scan and ultrasound biomicroscopy). The affected eye was
      enucleated, and pathologic study showed a hemorrhagic poorly differentiated
      neoplasm of the ciliary body. Subsequent patient evaluation revealed a primary
      testicular embryonal carcinoma with widespread metastasis. CONCLUSION: This case
      represents the first report of a metastasis from a testicular carcinoma to the
      ciliary body and the first tumor of this type to be associated with spontaneous
      hyphema.

PMID- 25390538
TI  - Treatment of cystoid macular edema in a patient with birdshot chorioretinopathy
      with bevacizumab.
AB  - PURPOSE: Birdshot chorioretinopathy is currently treated with either systemic
      immune modulation or intravitreal polytherapy. These regimens pose challenges to
      the clinician and patient such as adverse effects, chronic treatment and
      compliance, and failure of therapy. In a patient with birdshot chorioretinopathy
      and juxtaposed cystoid macular edema, the authors assessed the efficacy of
      bevacizumab for treatment after systemic therapy had failed. METHODS: A 48-year
      old woman was injected with intravitreal bevacizumab 10 times in her right eye
      with 4 weeks to 6 weeks intervening between injections. Improvement was monitored
      by best-corrected visual acuity and ocular coherence tomography. RESULTS: Visual
      acuity improved from 20/200 to 20/30 in the right eye, and foveal thickness
      improved from 638 MUm to 200 MUm. Visible signs of macular edema and inflammation
      completely disappeared. CONCLUSION: Bevacizumab monotherapy may improve visual
      acuity with resolution of macular edema in patients with birdshot
      chorioretinopathy that is refractory to traditional systemic therapy.

PMID- 25390539
TI  - Migration of intravitreal dexamethasone implant to anterior chamber.
AB  - PURPOSE: To describe two cases of migration of intravitreally injected
      dexamethasone implant into the anterior chamber. METHODS: Charts were reviewed of
      two patients who received sustained-release dexamethasone implant intravitreally
      for chronic intractable cystoid macular edema. RESULTS: Both patients had
      pseudophakic cystoid macular edema and a complicated clinical course before
      receiving the implant. Treatments before intravitreal injection of implant
      included topical nonsteroidal anti-inflammatory drugs, sub-Tenon triamcinolone
      injections, vitrectomy, and, in one case, intravitreal bevacizumab. Both patients
      responded well to triamcinolone injections but required repeated injections. This
      led to the decision to inject the implant. Within 2 weeks of injection, the
      implant was noted in the anterior chamber causing pain and decreased vision from
      corneal edema. Both patients underwent successful removal of the implant.
      CONCLUSION: Sustained-release intravitreal injectable implants can migrate freely
      in vitrectomized pseudophakic or aphakic eyes. Selection of a scleral-fixated
      steroid implant might be safer in such cases.

PMID- 25390540
TI  - The use of intravitreal ranibizumab to treat neovascular glaucoma because of
      retinal amyloid angiopathy in familial amyloidosis transthyretin v30m related.
AB  - PURPOSE: The purpose of this study to report a patient with amyloidotic
      angiopathy and neovascular glaucoma who was treated with intravitreal injection
      of ranibizumab followed by laser photocoagulation. METHODS: A 52-year-old liver
      transplanted woman with familial amyloidotic polyneuropathy presented with
      unilateral rubeosis iridis and neovascular glaucoma. A complete ocular
      examination and fluorescein and indocyanine green angiography were performed.
      RESULTS: Best-corrected visual acuity before injection was 0.05 (Snellen) in the
      left eye, and intraocular pressure was 42 mmHg. Fluorescein angiography showed
      vascular occlusion in the retinal periphery, focal staining of vessels, and
      microaneurysms. Indocyanine green angiography showed hyperfluorescent spots
      alongside the choroidal veins. Two days after receiving intravitreal injection of
      ranibizumab, the clinical picture regressed. The diagnosis of retinal amyloid
      angiopathy was made, and a peripheral retinal laser photocoagulation was done.
      The final best-corrected visual acuity after 2 years of follow-up was 0.4
      (Snellen) in the left eye. CONCLUSION: Intravitreal injections of ranibizumab
      should be evaluated for a potential role on the treatment of amyloid angiopathy
      neovascular glaucoma. Careful retinal periphery examination should be included in
      the ophthalmologic examination of all familial amyloidotic polyneuropathy
      patients.

PMID- 25390541
TI  - Retinal cases & brief reports 2012 scientific reviewers.

PMID- 25390542
TI  - Correction of vaginal vault prolapse using CapioTM suture capturing device: our
      experience.
AB  - AIM: Aim of the present study was to evaluate advantages and disadvantages of the
      sacrospinous ligament fixation (SSF) technique using the CapioTM suture capturing
      device (Boston Scientific, Natick, MA, USA) in a group of menopausal women
      affected by vaginal vault prolapse. METHODS: This was an observational,
      retrospective, cross-sectional study. Menopausal women with vaginal vault
      prolapse (grade >2) who had never before been treated to correct the vaginal
      prolapse received the SSF technique using the CapioTM suture capturing device.
      RESULTS: Forty-seven patients underwent unilateral (38.2%) or bilateral (61.8%)
      fixation, through the paravescical (65.9%) or pararectal (34.1%) route. Median
      follow-up was 18.5 months (range 3-34); follow-up visits were performed 30 days
      after the intervention, at 3, 6 and 12 months in the first postoperative year and
      every 6 months from then on. Other concomitant procedures such as cystopexy,
      rectopexy, correction of enterocele or vaginal paravaginal repair were performed
      as necessary. The procedure was successful in 89.3% of patients, with a resulting
      mean vaginal length of 7.1+/-2.4 cm, regardless of the approach used. Only 5
      patients suffered from prolapse recurrence. Main long-term complications were de
      novo and recurrent cystocele, observed mainly in patients who presented risk
      factors and with no significant differences related to the surgical procedure.
      CONCLUSION: The use of the CapioTM suture capturing device can simplify the SSF
      procedure compared with the traditional technique. The use of small devices
      requires less surgical dissection, reducing surgery time. Future studies are
      required to solve open issues.

PMID- 25390543
TI  - Breast conservation surgery and the definition of adequate margins: more is not
      better...it's just more.

PMID- 25390544
TI  - Purification and characterization of broccoli (Brassica oleracea var. italica)
      myrosinase (beta-thioglucosidase glucohydrolase).
AB  - Myrosinase (beta-thioglucosidase glucohydrolase, EC 3.2.1.147) from broccoli
      (Brassica oleracea var. italica) was purified by ammonium sulfate precipitation
      followed by concanavalin A affinity chromatography, with an intermediate dialysis
      step, resulting in 88% recovery and 1318-fold purification. These are the highest
      values reported for the purification of any myrosinase. The subunits of broccoli
      myrosinase have a molecular mass of 50-55 kDa. The native molecular mass of
      myrosinase was 157 kDa, and accordingly, it is composed of three subunits. The
      maximum activity was observed at 40  degrees C and at pH below 5.0. Kinetic
      assays demonstrated that broccoli myrosinase is subjected to substrate (sinigrin)
      inhibition. The Michaelis-Menten model, considering substrate inhibition, gave
      Vmax equal to 0.246 MUmol min(-1), Km equal to 0.086 mM, and K(I) equal to 0.368
      mM. This is the first study about purification and characterization of broccoli
      myrosinase.

PMID- 25390545
TI  - Adhesive polydopamine coated avermectin microcapsules for prolonging foliar
      pesticide retention.
AB  - In this work, we report a conceptual strategy for prolonging foliar pesticide
      retention by using an adhesive polydopamine (PDA) microcapsule to encapsulate
      avermectin, thereby minimizing its volatilization and improving its residence
      time on crop surfaces. Polydopamine coated avermectin (Av@PDA) microcapsules were
      prepared by emulsion interfacial-polymerization and characterized by Fourier
      transform infrared spectroscopy, energy dispersive X-ray spectroscopy, field
      emission scanning electron microscope, and transmission electron microscopy. The
      in situ synthesis route confers Av@PDA microcapsules with remarkable avermectin
      loading ability of up to 66.5% (w/w). Kinetic study of avermectin release
      demonstrated that Av@PDA microcapsules exhibit sustained- and controlled-release
      properties. The adhesive property of Av@PDA microcapsules on different surfaces
      was verified by a comparative study between Av@PDA and passivated Av@SiO2 and
      Av@PDA@SiO2 capsules with silica shell. Moreover, PDA shell could effectively
      shield UV irradiation and so protect avermectin from photodegradation, making it
      more applicable for foliar spraying. Meanwhile, it is determinated that Av@PDA
      microcapsules have good mechanical stability property. 

PMID- 25390546
TI  - Studies of the antiferrodistortive transition in EuTiO3.
AB  - Structural studies of EuTiO3, conducted using synchrotron x-ray powder
      diffraction, reveal the sensitivity of this material to defects. The presence of
      a single tetragonal-cubic (I4/mcm-Pm-3m) transition is confirmed. Neutron
      diffraction measurements show EuTiO3 to have a G-type antiferromagnetic
      arrangement. Examinations of the symmetry-adapted tetragonal strains demonstrate
      that the stoichiometry impacts on the continuous nature of this. The impact of
      defects on the electrical conductivity and magnetodielectric effect is also
      described. 

PMID- 25390547
TI  - Molecular design strategy toward diarylethenes that photoswitch with visible
      light.
AB  - Photoactive molecules that reversibly switch upon visible light irradiation are
      one of the most attractive targets for biological as well as imaging
      applications. One possible approach to prepare such photoswitches is to extend pi
      conjugation length of molecules and shift the absorption bands to longer
      wavelengths. Although several attempts have been demonstrated based on this
      approach for diarylethene (DAE) photoswitches, photoreactivity of the DAE
      derivatives is dramatically suppressed when the conjugation length is extended by
      connecting aromatic dyes at the side positions of aryl groups in the DAE unit. In
      this study, we successfully prepared a visible-light reactive DAE derivative by
      introducing an aromatic dye at the reactive carbon atom of the DAE unit,
      optimizing orbital level of each component, and controlling the mutual
      orientation of the aromatic dye and the DAE unit. The DAE derivative (3)
      undergoes a photocyclization reaction upon irradiation with 560 nm light and the
      closed-isomer converts to the open-ring isomer upon irradiation with 405 nm
      light. The high photoconversion yields (>90%) were achieved for both
      photocyclization and photocycloreversion reactions. The photoreactivity induced
      by visible light irradiation and the molecular design strategy were discussed
      based on theoretical calculations. 

PMID- 25390548
TI  - Quality of vision after excimer laser phototherapeutic keratectomy with
      intraoperative mitomycin-C for Salzmann nodular degeneration.
AB  - OBJECTIVE: To assess the effect of excimer laser phototherapeutic keratectomy
      (PTK) with intraoperative mitomycin-C (MMC) on the quality of vision in patients
      with Salzmann nodular degeneration (SND). METHODS: Thirteen eyes of 12 patients
      were enrolled in the study between December 2010 and March 2012. Uncorrected and
      best-corrected Snellen distance visual acuities were measured at every visit.
      Contrast sensitivity and manifest refraction were measured preoperatively, at 1
      month and at 3 months. Corneal topography, Galilei dual Scheimpflug imaging, VISX
      WaveScan, and ultrasound central corneal pachymetry were measured preoperatively
      and at 3 months after PTK procedure. RESULTS: Contrast sensitivity was
      statistically significantly better both at 1 month (P<0.01) and 3 months
      (P<0.01). Postoperatively, there was 46% increase in eyes with measurable corneal
      topography, 69% increase in Galilei dual Scheimpflug imaging, and a 77% increase
      in WaveScan measurements. The third-order (P<0.01) and total corneal higher-order
      aberrations (HOAs) (P=0.01) were significantly lower postoperatively compared
      with the preoperative corneal aberrations measured on Galilei dual Scheimpflug
      imaging. CONCLUSIONS: Significant improvement in contrast sensitivity and corneal
      HOAs was seen after PTK for SND. Phototherapeutic keratectomy with MMC can be
      considered as an effective procedure in the improvement of the quality of vision
      in patients with SND.

PMID- 25390550
TI  - Mechanisms for acute corneal hydrops and perforation.
AB  - Acute corneal hydrops (ACH) and perforation in corneal thinning diseases are the
      consequences of exposure to distending intraocular pressure (IOP) forces that are
      in excess of corneal resistance to them. Apart from thinning, resistance to these
      forces may be reduced by disease-related tissue changes, such as corneal
      scarring, which could lower resistance to IOP. Eye rubbing trauma has sometimes
      been found to be associated with ACH and perforation. This association is not
      surprising given that the combination of rubbing-related mechanical tissue trauma
      and the associated increased distending stress of higher IOP seem likely to
      increase the risk of complications. Many cases of ACH and perforation are
      described as spontaneous, but this classification may be the consequence of not
      considering the multiple potential mechanisms for IOP elevation such as coughing,
      sneezing, nose blowing, and sneeze suppression in addition to those related to
      eye rubbing/wiping/massaging/touching as well as changes in body orientation,
      strenuous exercise, and wearing swimming goggles for example. Classification of
      ACH or perforation as spontaneous may lead patients to assume that nothing can be
      done to avoid these complications. Patients with corneal thinning diseases who
      are counseled regarding the potential precipitating mechanisms for IOP elevation
      will have the opportunity of reducing exposure to them and the risk of the
      associated complications. In addition, when ACH or perforation occur, faster
      resolution of edema and wound healing may depend on reducing potentially
      exacerbating exposures to mechanisms for IOP elevation.

PMID- 25390549
TI  - The core mechanism of dry eye disease is inflammation.
AB  - PURPOSE: The purpose of this article is to review the evidence for the hypothesis
      that the core mechanism of dry eye disease (DED) is inflammation, including
      evidence from recent basic, clinical, and translational research involving human
      patients, animal models, and cell cultures. METHODS: Using the key words "dry eye
      + inflammation," the authors conducted a comprehensive search of the PubMed and
      Web of Science databases for scientific articles published in English between
      January 1, 1900 and August 30, 2013 on the role of inflammation in DED in cell
      cultures, animal models, and humans. The resulting articles were then categorized
      and reviewed. RESULTS: The literature search revealed a total of 458
      publications, almost all published after 1992. The percentages of original
      studies and review articles are 77.29% (354) and 22.71% (104), respectively.
      Among the original studies, the number of reports on human DED is 200 (43.7%), on
      animal models is 115 (25.1%), and cell cultures is 39 (8.5%). A yearly
      distributing plot revealed that 76% were published from 2003 to 2011, 53% from
      2008 to 2012, and 11% during the first 9 months of 2013. This distribution
      signifies a rapidly growing awareness of the importance of inflammation in DED
      pathogenesis. CONCLUSIONS: Inflammation plays a key role in the pathogenesis of
      DED as evidenced by research using tissue culture, animal models, and subjects
      with DED. Developing biomarkers for inflammation of the ocular surface will
      provide improved understanding of the mechanisms leading to DED, classification
      of the severity of DED, and objective metrics for outcome measures of treatment.
      The chronicity of the disease suggests that dysregulation of immune mechanisms
      leads to a cycle of continued inflammation, accompanied by alterations in both
      innate and adaptive immune responses. Given the underlying mechanism for DED,
      developing effective and safe anti-inflammatory treatments is likely to be
      beneficial for patients with DED.

PMID- 25390551
TI  - Original letter: Interactions of contact lenses with multipurpose disinfecting
      solution containing PHMB.

PMID- 25390552
TI  - Response: Interactions of contact lenses with a multipurpose disinfecting
      solution containing PHMB.

PMID- 25390553
TI  - Clinical outcomes of glued transscleral fixated intraocular lens in functionally
      one-eyed patients.
AB  - PURPOSE: To analyze the indications, visual outcome, mental status, and quality
      of life after glued transscleral fixated intraocular lens (IOL) in functionally
      one-eyed individuals. SETTING: Dr Agarwal's Eye Hospital and Eye Research Centre,
      Chennai, India. DESIGN: Prospective observational comparative case series.
      METHODS: Patients with one functioning eye with surgical indications (aphakia,
      luxated IOL, or dislocated lens) and the fellow eye with no perception of light
      were included. Indications, uncorrected distant visual acuity (UDVA), corrected
      distant visual acuity (CDVA), mental status (Amsterdam Preoperative Anxiety and
      Information Scale) and quality of life (visual function scoring VF-14) were
      assessed. Outcomes of nonsurgical and surgical management were evaluated and
      compared. RESULTS: Of 22 patients, 10 (45.4%) patients underwent glued IOL (group
      A) and 12 (54.5%) wore spectacles (group B). There was a strong association
      between the initial clinical presentation and management (chi, P=0.000).
      Subluxated cataract and dislocated lens (or IOL) required surgical treatment.
      Postoperative aphakia with adequate spectacle correction were conservatively
      treated. There was change (P=0.005) in UDVA and CDVA after glued IOL surgery.
      There was no loss of CDVA. There was difference between the 2 groups in reading
      small prints (P=0.021), sporting activities (P=0.000), and night driving
      (P=0.000). Surgical anxiety was higher in group B (P=0.014). Females were more
      anxious than the males (P=0.014). There was an association of increasing age and
      the decision for nonsurgical management (chi, P=0.005). CONCLUSION: Glued
      transscleral fixated IOL can be safely performed in one-eyed patients for
      specific indications to provide good functional results.

PMID- 25390554
TI  - Pancreatic neuroendocrine tumors: targeting the molecular basis of disease.
AB  - PURPOSE OF REVIEW: Pancreatic neuroendocrine tumors (pNETs) are a rare and
      heterogeneous group of neoplasia. Presentation of these tumors can vary widely.
      Current treatment modalities range from potentially curative surgical
      interventions in localized disease to the use of varied hormonal analogues,
      cytotoxic agents and targeted therapy for the management of locally advanced and
      metastatic disease. With such a wide variety of therapeutic modalities,
      clinicians are faced with the task of building an effective and comprehensive
      treatment strategy for their patients. RECENT FINDINGS: Targeted therapy for pNET
      is limited to sunitinib and everolimus. There have been a number of important
      studies assessing the efficacy of other targeted agents, in addition to the
      conjugation of these agents in the management of advanced pNET. This review will
      stand to highlight currently available targeted therapies for the treatment of
      advanced pNET. SUMMARY: The use of targeted agents in the management of advanced
      pNET has significant potential to change the current standard of care. In
      addition to the use of long-acting somatostatin analogues, targeting the
      mammalian target of rapamycin and vascular endothelial growth factor pathways can
      be well tolerated and may lead to long periods of disease control in a wide
      variety of neuroendocrine tumors involving the pancreas.

PMID- 25390555
TI  - What is the appropriate role of minimally invasive vs. open surgery for small
      adrenocortical cancers?
AB  - PURPOSE OF REVIEW: The role of endoscopic adrenalectomy for adrenocortical
      carcinoma is the most controversial and debated points in adrenal surgery. We
      reviewed the most recent literature on this topic. RECENT FINDINGS: From the
      amount of available data (even if not conclusive), the following could be
      extrapolated: first, for patients with apparently localized disease the adrenal
      gland should be removed en bloc with the entire retroperitoneal fat pad, which
      also includes some periadrenal lymph nodes, but no extended resection is
      necessary in absence of involvement of adjacent structures; second, in
      experienced centers, oncologic outcome for endoscopic adrenalectomy is not
      inferior to open adrenalectomy when strict selection criteria and the principles
      of oncologic surgery are respected. When performed by nonexperienced surgeons,
      endoscopic adrenalectomy may be associated with a higher rate of positive margin
      and local recurrence; third, patients observed at specialized referral centers
      receive a more accurate preoperative workup that allows a better operative
      planning and a more comprehensive postoperative treatment. SUMMARY: Although
      waiting for further more exhaustive studies, we think that for suspected
      adrenocortical carcinoma, smaller than 8-10 cm and without pre or intraoperative
      evidence of local invasion, endoscopic adrenalectomy in a referral center seems
      to be an acceptable option.

PMID- 25390556
TI  - Thyroglobulin antibody status and differentiated thyroid cancer: what does it
      mean for prognosis and surveillance?
AB  - PURPOSE OF REVIEW: To provide an overview of the clinical utility of
      thyroglobulin antibody (TgAb) measurements in the management of differentiated
      thyroid cancer (DTC), taking into consideration the methodological concerns
      associated with these measurements. RECENT FINDINGS: In the past 1 to 2 years,
      clinical studies have added to our understanding of the limitations and pitfalls
      associated with TgAb assay methods, the association of autoimmune thyroid disease
      with DTC, the prognostic significance of TgAb positivity and the clinical utility
      of the trend of TgAb measurements as a surrogate tumor marker. SUMMARY: TgAb
      trends appear to have clinical utility as a surrogate tumor marker in the
      surveillance of TgAb-positive DTC patients. The prognostic significance of TgAb
      status (positive/negative) as well as the nature and clinical significance of the
      association of autoimmune thyroid disease with DTC is less clear.

PMID- 25390557
TI  - Association of Hashimoto's thyroiditis and thyroid cancer.
AB  - PURPOSE OF REVIEW: The association of Hashimoto's thyroiditis and thyroid cancer
      remains an active focus of research and controversy. Since it was first proposed
      in 1955, numerous studies have explored the epidemiology and etiology of these
      concurrent disease processes. RECENT FINDINGS: The lymphocytic infiltration of
      Hashimoto's thyroiditis is frequently encountered in thyroid glands resected for
      a neoplasm. The most frequent association is noted with papillary thyroid cancer.
      Several recent studies performed on patients undergoing thyroidectomy with
      coexisting Hashimoto's thyroiditis report an increased prevalence of papillary
      thyroid cancer, with a favorable disease profile and an improved prognosis,
      particularly in women. Conversely, some population-based studies using fine
      needle aspiration biopsy data report no linkage between serologic Hashimoto's
      thyroiditis and thyroid cancer, yet they are limited by the lack of definitive
      pathology. On the other hand, the significantly increased incidence of primary
      thyroid lymphomas in patients with Hashimoto's thyroiditis strongly suggests a
      pathogenetic link between this autoimmune disorder and malignant thyroid
      lymphoma. SUMMARY: The lymphocytic infiltration of Hashimoto's thyroiditis is
      frequently associated with papillary thyroid cancer and may indeed be a risk
      factor for developing this type of cancer. Nonetheless, a pathogenesis linking
      these diseases remains unclear. The relationship between thyroid lymphoma and
      Hashimoto's thyroiditis appears to be well established.

PMID- 25390558
TI  - National armies for global health?

PMID- 25390559
TI  - Health inequities in the USA: closing the gaps.

PMID- 25390560
TI  - Health of the homeless.

PMID- 25390561
TI  - Low carbohydrate diets: going against the grain.

PMID- 25390562
TI  - Ombudsman's report on the letter by Manduca and others.

PMID- 25390564
TI  - US federal health agencies questioned over Ebola response.

PMID- 25390565
TI  - East Timor striving for universal access to health care.

PMID- 25390566
TI  - John Geddes: design for life.

PMID- 25390567
TI  - Dorothy Hodgkin: on proteins and patterns.

PMID- 25390568
TI  - Anthony John McMichael.

PMID- 25390569
TI  - Ebola control: effect of asymptomatic infection and acquired immunity.

PMID- 25390570
TI  - Conflict and drug-resistant tuberculosis in Ukraine.

PMID- 25390571
TI  - Making primary care people-centred.

PMID- 25390572
TI  - Making primary care people-centred.

PMID- 25390573
TI  - Alteplase for ischaemic stroke.

PMID- 25390574
TI  - Cancer in the 25*25 non-communicable disease targets.

PMID- 25390575
TI  - Challenges for Colombian medical journals.

PMID- 25390579
TI  - Health interventions for people who are homeless.
AB  - Homelessness has serious implications for the health of individuals and
      populations. Primary health-care programmes specifically tailored to homeless
      individuals might be more effective than standard primary health care. Standard
      case management, assertive community treatment, and critical time intervention
      are effective models of mental health-care delivery. Housing First, with
      immediate provision of housing in independent units with support, improves
      outcomes for individuals with serious mental illnesses. Many different types of
      interventions, including case management, are effective in the reduction of
      substance misuse. Interventions that provide case management and supportive
      housing have the greatest effect when they target individuals who are the most
      intensive users of services. Medical respite programmes are an effective
      intervention for homeless patients leaving the hospital. Although the scientific
      literature provides guidance on interventions to improve the health of homeless
      individuals, health-care providers should also seek to address social policies
      and structural factors that result in homelessness. 

PMID- 25390580
TI  - Type B Insulin-resistance syndrome: a cause of reversible autoimmune
      hypoglycaemia.

PMID- 25390582
TI  - Coverage and disruption of phospholipid membranes by oxide nanoparticles.
AB  - We studied the interactions of silica and titanium dioxide nanoparticles with
      phospholipid membranes and show how electrostatics plays an important role. For
      this, we systematically varied the charge density of both the membranes by
      changing their lipid composition and the oxide particles by changing the pH. For
      the silica nanoparticles, results from our recently presented fluorescence
      vesicle leakage assay are combined with data on particle adsorption onto
      supported lipid bilayers obtained by optical reflectometry. Because of the strong
      tendency of the TiO2 nanoparticles to aggregate, the interaction of these
      particles with the bilayer was studied only in the leakage assay. Self-consistent
      field (SCF) modeling was applied to interpret the results on a molecular level.
      At low charge densities of either the silica nanoparticles or the lipid bilayers,
      no electrostatic barrier to adsorption exists. However, the adsorption rate and
      adsorbed amounts drop with increasing (negative) charge densities on particles
      and membranes because of electric double-layer repulsion, which is confirmed by
      the effect of the ionic strength. SCF calculations show that charged particles
      change the structure of lipid bilayers by a reorientation of a fraction of the
      zwitterionic phosphatidylcholine (PC) headgroups. This explains the affinity of
      the silica particles for pure PC lipid layers, even at relatively high particle
      charge densities. Particle adsorption does not always lead to the disruption of
      the membrane integrity, as is clear from a comparison of the leakage and
      adsorption data for the silica particles. The attraction should be strong enough,
      and in line with this, we found that for positively charged TiO2 particles
      vesicle disruption increases with increasing negative charge density on the
      membranes. Our results may be extrapolated to a broader range of oxide
      nanoparticles and ultimately may be used for establishing more accurate
      nanoparticle toxicity assessments and drug-delivery systems. 

PMID- 25390578
TI  - The health of homeless people in high-income countries: descriptive epidemiology,
      health consequences, and clinical and policy recommendations.
AB  - In the European Union, more than 400,000 individuals are homeless on any one
      night and more than 600,000 are homeless in the USA. The causes of homelessness
      are an interaction between individual and structural factors. Individual factors
      include poverty, family problems, and mental health and substance misuse
      problems. The availability of low-cost housing is thought to be the most
      important structural determinant for homelessness. Homeless people have higher
      rates of premature mortality than the rest of the population, especially from
      suicide and unintentional injuries, and an increased prevalence of a range of
      infectious diseases, mental disorders, and substance misuse. High rates of non
      communicable diseases have also been described with evidence of accelerated
      ageing. Although engagement with health services and adherence to treatments is
      often compromised, homeless people typically attend the emergency department more
      often than non-homeless people. We discuss several recommendations to improve the
      surveillance of morbidity and mortality in homeless people. Programmes focused on
      high-risk groups, such as individuals leaving prisons, psychiatric hospitals, and
      the child welfare system, and the introduction of national and state-wide plans
      that target homeless people are likely to improve outcomes.

PMID- 25390583
TI  - Autofluorescence characteristics of congenital hypertrophy of the retinal pigment
      epithelium.
AB  - PURPOSE: To report the autofluorescence features of congenital hypertrophy of the
      retinal pigment epithelium (CHRPE). METHODS: Four patients with CHRPE were
      evaluated using autofluorescence in a camera-based system. RESULTS: All CHRPE
      lesions studied had well demarcated borders and were hypoautofluorescent.
      Presence of a hypopigmented halo and lacunae did not alter the homogeneous
      hypofluorescence. CONCLUSION: Hypoautofluorescence confirmed the known absence of
      lipofuscin in the retinal pigment epithelium cells of CHRPE lesions.
      Autofluorescence imaging may provide useful information in evaluating pigmented
      lesions of the fundus.

PMID- 25390584
TI  - Vitreous hemorrhage associated with interferon-a therapy for chronic hepatitis C.
AB  - BACKGROUND: Interferons (IFNs) have been used medically, but ocular side effects
      have been associated with their use. METHODS: Case report. RESULTS: We report a
      case of sudden loss of vision due to vitreous hemorrhage during IFN alpha-2b
      therapy; resolution occurred with drug discontinuation. CONCLUSION: Our case
      suggests that vitreous hemorrhage may be added to the myriad of retinal vascular
      ischemic changes known to be secondary to IFN therapy as adverse effects.

PMID- 25390585
TI  - Nonfamilial vitreous amyloidosis diagnosed by portable sutureless vitrectomy.
AB  - PURPOSE: To describe a case of primary nonfamilial vitreous amyloidosis and a
      novel technique for expediting vitreous biopsy. DESIGN: Interventional case
      report. CASE: A 43-year-old man presented with progressive deterioration of
      vision and was found to have bilateral vitreous opacities. A systemic medical
      workup including family history was noncontributory. Given a high clinical
      suspicion of vitreous amyloidosis, the decision was made to obtain a vitreous
      biopsy for ultrastructural study. An office-based pars plana sutureless
      vitrectomy was performed. Pathologic study of the vitreous specimen confirmed the
      diagnosis of amyloidosis. CONCLUSION: Vitreous amyloid deposition may occur with
      neither systemic involvement nor family history. Sutureless pars plana vitrectomy
      may facilitate diagnosis while saving time and expense for both the physician and
      the patient.

PMID- 25390586
TI  - Vitreomacular traction syndrome with an outer macular hole.
AB  - PURPOSE: To describe a patient with a large idiopathic partial-thickness macular
      hole involving the outer layers of the retina. METHODS: We performed complete
      ophthalmologic examination, including fluorescein angiography, B-scan
      ultrasonography, and optical coherence tomography, on an 81-year-old woman who
      was referred to our department with the clinical suspicion of a stage 3 full
      thickness macular hole in the left eye. RESULTS: After complete ophthalmologic
      examination, the patient was diagnosed with vitreomacular traction syndrome due
      to a prefoveal partial posterior vitreous detachment causing tangential outward
      traction on the fovea. In this case, vitreomacular traction was associated with
      macular detachment and was complicated by retinoschisis and an idiopathic partial
      thickness macular hole, in the absence of either high myopia or an optic nerve
      pit. CONCLUSION: To our knowledge, this is the first reported case of a large
      idiopathic partial-thickness macular hole sharing common features with macular
      schisis, in the absence of either high myopia or an optic disk pit.

PMID- 25390587
TI  - Closure of a macular hole associated with a retinal arterial aneurysm without
      surgical intervention.
AB  - PURPOSE: To report a case in which a macular hole (MH) associated with a ruptured
      retinal arteriolar aneurysm (RAM) closed without surgical intervention. PATIENT
      AND RESULTS: A 65-year-old woman presented complaining of sudden visual loss due
      to vitreous hemorrhage in the left eye. Correctable visual acuity in the left eye
      was 2/100 at the initial visit. Three weeks later, the vitreous hemorrhage had
      resolved, revealing an MH, serous retinal detachment, and subretinal hemorrhage
      associated with a ruptured RAM. Laser photocoagulation was applied to the RAM to
      promote absorption of the subretinal fluid. Two months after onset, the MH closed
      with resolution of the exudative retinal lesions and recovery of vision to 20/60.
      CONCLUSIONS: The present case indicates that closure of an MH can take place
      within a couple of months without surgical intervention. This suggests that
      observation without surgical intervention may be advocated when an MH is
      associated with a ruptured RAM and massive subretinal hemorrhage spares the
      macula.

PMID- 25390588
TI  - Lamellar macular hole: a new indication for vitrectomy with ilm peeling?
AB  - PURPOSE: Visual loss due to lamellar macular holes has been considered
      insuperable in the past. The authors report anatomic and functional improvement
      after surgery for an inner lamellar macular hole. METHODS: A 47-year-old woman
      with mild nuclear sclerosis and posterior subcapsular cataract and an inner
      lamellar macular hole presented with low visual acuity unexplained by the degree
      of cataract. She underwent phacoemulsification with intraocular lens
      implantation, vitrectomy, internal limiting membrane peeling, and gas tamponade.
      RESULTS: Pre- and postoperative biomicroscopic examination and optical coherence
      tomography confirmed anatomic restoration of the foveal contour that was
      associated with marked improvement in visual acuity, maintained over the follow
      up period of 7 months. CONCLUSIONS: Surgery may be an effective option for inner
      lamellar macular holes causing significant visual impairment.

PMID- 25390589
TI  - Management of optic disk pit-associated macular detachment with tisseel fibrin
      sealant.
AB  - BACKGROUND: Optic disk pit-associated macular detachment is a challenging
      condition to treat. Many surgical methods have been used to treat this condition
      with varying degrees of success. METHODS: We managed optic disk pit-associated
      macular detachment in three cases with pars plana vitrectomy, fluid-air exchange,
      drainage of subretinal fluid through the optic disk pit, application of Tisseel
      fibrin sealant (Baxter Healthcare Corporation, CA) to the optic disk pit, C3F8
      gas injection, and postoperative prone positioning. RESULTS: All three patients
      maintained flat maculae and had improved vision. Patient 3 had postoperative
      macular hole formation. This was managed successfully with pars plana vitrectomy,
      internal limiting membrane peeling, fluid-air exchange, and C3F8 gas injection.
      CONCLUSION: Our case series suggest that Tisseel fibrin sealant in conjunction
      with pars plana vitrectomy can be used successfully for management of optic pit
      disk-associated macular detachments.

PMID- 25390590
TI  - Vasoproliferative tumor of the retina in association with spontaneously
      reattached rhegmatogenous retinal detachment.
AB  - PURPOSE: To report a case of spontaneously reattached rhegmatogenous retinal
      detachment seen in association with a vascularized tumor fitting the clinical
      features of a vasoproliferative tumor. METHODS: Case report. RESULTS: A 38-year
      old man presented with retinal findings compatible with those seen in patients
      with spontaneously reattached rhegmatogenous retinal detachments (presence of
      pigment in the vitreous, multiple high-water marks, chorioretinal and retinal
      pigment epithelial changes, and subretinal fibrosis) and a vascularized tumor
      fitting the clinical features of a vasoproliferative tumor. CONCLUSION: A
      vasoproliferative tumor of the retina can arise after spontaneous resolution of a
      rhegmatogenous retinal detachment.

PMID- 25390591
TI  - Unusual case of diffuse choroidal melanoma masquerading as atypical central
      serous chorioretinopathy.
AB  - PURPOSE: To describe an unusual case of diffuse circumpapillary choroidal
      melanoma masquerading as atypical central serous chorioretinopathy, and to
      describe fluorescein angiographic and optical coherence tomography
      characteristics of this diffuse choroidal melanoma. DESIGN: Interventional case
      report. METHODS: A 46-year-old human immunodeficiency virus-positive man
      presented with an 11-month history of decreased vision and the absence of an
      elevated choroidal lesion. The patient failed to return for follow-up. RESULTS:
      Thirteen months after his initial presentation, circumpapillary diffuse choroidal
      melanoma was diagnosed. The patient underwent enucleation. No extrascleral
      extension was present. CONCLUSIONS: Imaging characteristics on fluorescein
      angiography or optical coherence tomography may be of diagnostic value to aid the
      ophthalmologist in earlier detection of diffuse choroidal melanomas.

PMID- 25390592
TI  - Bilateral ocular manifestations of aggressive cutaneous metastatic melanoma.
AB  - PURPOSE: To report an unusual case of aggressive cutaneous malignant melanoma
      metastatic to both eyes. The case is also remarkable for differences from the
      bilateral diffuse uveal melanocytic proliferation syndrome (BDUMP). DESIGN:
      Observational case report. METHODS: The authors studied the case of a 56-year-old
      man with decreased vision and floaters in the left eye. He recently had been
      diagnosed with metastatic cutaneous malignant melanoma. RESULTS: Clinical
      examination, fundus photography, and ultrasonography revealed widespread
      metastases to the choroid, ciliary body, iris, and eyelid. A-scan revealed medium
      internal reflectivity of a collar-button lesion in the ciliary body, consistent
      with metastatic disease. CONCLUSIONS: Despite the rarity of BDUMP and bilateral
      intraocular malignant cutaneous or uveal melanoma metastases, these diagnoses
      should be considered when diffuse bilateral melanocytic lesions are present.
      Ultrasonography and metastatic workup are critically important to help
      distinguish these disease entities.

PMID- 25390593
TI  - Macular epiretinal membrane formation after low-dose radiation exposure in a
      child with papilledema from a craniopharyngioma.
AB  - PURPOSE: To describe a child with a craniopharyngioma and papilledema who
      developed a unilateral epiretinal membrane (ERM) after completing radiation
      therapy for his tumor. METHODS: A clinical case is presented including fundus
      images of the patient's left eye and radiotherapy dosimetry curves. RESULTS: The
      patient presented with unilateral formation of an ERM after resolution of
      papilledema from a craniopharyngioma. Dosimetry curves from radiotherapy showed
      low-dose exposure in the region of ERM formation in the left eye at the level of
      500 cGy to 1,000 cGy. CONCLUSIONS: The concordance of the low-dose radiation with
      the site of ERM formation suggests a possible contribution of radiotherapy
      treatment to the formation of the macular epiretinal tissue in this patient.

PMID- 25390594
TI  - Age-related macular degeneration with massive subretinal hemorrhage easily
      removed through a retinal break.
AB  - PURPOSE: To report a case of age-related macular degeneration (AMD) with massive
      subretinal hemorrhage easily removed through a retinal break. CASE REPORT: A 57
      year-old Japanese man with a massive subretinal hemorrhage in an eye with AMD
      developed a rhegmatogenous retinal detachment after intraocular gas injection.
      The subretinal hemorrhage was easily removed using perfluorocarbon liquid during
      vitrectomy, and the retinal degeneration was minimal. CONCLUSION: Rhegmatogenous
      retinal detachment is an unfavorable complication after intraocular gas injection
      for the treatment of AMD. In our case, the subretinal hemorrhage was easily
      removed, and visual recovery was possible to some degree.

PMID- 25390595
TI  - Spontaneous scleral rupture adjacent to retinochoroidal coloboma.
AB  - BACKGROUND: Spontaneous scleral rupture in association with retinochoroidal
      coloboma is a rare and poorly understood event, with few reports in the
      literature. METHODS: Interventional case report. RESULTS: A 40-year-old man had a
      spontaneous decline in visual acuity with hypotony in the right eye.
      Photographic, fluorescein angiographic, optical coherence tomographic,
      ultrasonographic, and computed tomographic findings demonstrated that the cause
      was spontaneous rupture of ectatic sclera adjacent to a retinochoroidal coloboma.
      Surgical repair with primary suture imbrication and support with a segmental
      scleral buckle restored the intraocular pressure and baseline visual acuity.
      CONCLUSIONS: The adjacent but distinct locations of the retinochoroidal coloboma
      and ectatic sclera in this case suggest that during embryogenesis a full
      thickness defect was present in the eye wall, but due to differential growth
      rates, the scleral and retinochoroidal defects ceased to be superimposed.
      Persistent hypotony implies continued flow of liquefied vitreous or aqueous
      through the defect. Suture imbrication and scleral buckling can be a successful
      treatment option.

PMID- 25390596
TI  - Tilted disk syndrome with superior staphyloma.
AB  - BACKGROUND: Tilted disk syndrome is a common condition that consists of
      inferonasal tilting of the optic disk and is usually associated with staphyloma
      in the inferonasal fundus. CASE REPORT: We describe a 50-year-old woman whose
      fundus exhibited, in both eyes, all the characteristics of tilted disk syndrome
      but in an upside-down pattern: superior instead of inferior staphyloma and
      thinning of the retinal pigment epithelium, a superior instead of an inferonasal
      crescent, and an inferior instead of a superior visual field defect. CONCLUSION:
      We have no satisfactory explanation for this unusual case.

PMID- 25390597
TI  - Sarcoid choroiditis simulating birdshot chorioretinopathy.
AB  - PURPOSE: To report an atypical presentation of sarcoidosis simulating birdshot
      chorioretinopathy. DESIGN: Observational case report. METHODS: Review of the
      clinical, laboratory, photographic, and histopathologic records of a patient with
      sarcoidosis. RESULTS: A 56-year-old white woman was evaluated for uveitis in both
      eyes. Dilated funduscopic examination of both eyes revealed numerous oval and
      irregular hypopigmented chorioretinal lesions located inferior nasally radiating
      from the optic nerve that were virtually identical to the typical funduscopic
      appearance of birdshot chorioretinopathy. The patient was lost to follow-up and
      returned 5 years later. In the interim, the patient underwent mediastinal lymph
      node biopsy that showed noncaseating granulomas consistent with sarcoidosis. The
      serum angiotensin-converting enzyme level was normal, and results of HLA- A29
      testing were negative. CONCLUSIONS: Sarcoidosis can cause choroidal lesions
      similar to those of birdshot choroidopathy. Clinicians should consider
      sarcoidosis in the differential diagnosis of birdshot chorioretinopathy, and
      patients initially diagnosed with birdshot choroidopathy should also undergo
      workup for sarcoidosis.

PMID- 25390598
TI  - Topical nepafenac 0.1% for treatment of chronic uveitic cystoid macular edema.
AB  - PURPOSE: To describe the efficacy of nepafenac ophthalmic suspension 0.1%
      (Nevanac; Alcon Laboratories, Inc.) for treating cystoid macular edema (CME)
      resulting from uveitis. DESIGN: Interventional case series METHODS: : Three
      patients with a history of decreased visual acuity due to uveitic CME despite
      previous treatment with topical steroids or traditional nonsteroidal
      antiinflammatory drugs, intravitreal triamcinolone acetonide (Kenalog; Bristol
      Myers Squibb), or immunosuppressive agents were given topical nepafenac 0.1%.
      Patients were monitored for clinical improvement, decreased retinal thickness by
      optical coherence tomography, and improved Snellen visual acuity. RESULTS: For
      all three patients, treatment with topical nepafenac for 4 weeks to 3 months led
      to improvement in visual acuity and decrease in retinal thickness. CONCLUSIONS:
      The improved visual acuity and decreased retinal thickness in these patients
      suggest that nepafenac is an effective treatment of inflammation and CME in the
      posterior segment of the eye for patients with chronic uveitis.

PMID- 25390599
TI  - Optical coherence tomography of retinal pigment epithelium folds.
AB  - PURPOSE: To report the optical coherence tomography (OCT) findings in retinal
      pigment epithelium (RPE) folds. METHODS: Fluorescein and/or indocyanine green
      angiography, and OCT were performed in four consecutive patients presenting RPE
      folds with typical fingerprint pattern of RPE detachment. RESULTS: In the 4
      cases, OCT allowed direct visualization of the folds. CONCLUSION: OCT valited the
      initial hypothesis by Schatz et al, who interpreted the fingerprint pattern as
      RPE folds.

PMID- 25390600
TI  - Seronegative west nile meningoencephalitis diagnosed by ophthalmologic
      examination with subsequent seroconversion.
AB  - PURPOSE: To describe a case of seronegative West Nile virus (WNV)
      meningoencephalitis definitively diagnosed with ophthalmologic examination and
      confirmatory repeat laboratory testing. DESIGN: Diagnostic case report. METHODS:
      A patient with negative serologic testing for severe viral meningoencephalitis
      presented with photophobia and blurred vision 2 months after initial
      presentation. RESULTS: Examination revealed all the classic ocular findings of
      WNV. Repeat serologic testing confirmed positive titers for WNV. CONCLUSIONS: WNV
      may initially present as a severe meningoencephalitis with negative serology.
      Ophthalmic examination, particularly in symptomatic patients, may help with
      diagnosis. The ophthalmologist may play a critical role in evaluation of possible
      WNV meningoencephalitis.

PMID- 25390601
TI  - Optical coherence tomography of a subretinal granuloma in simultaneous visceral
      and ocular larva migrans.
AB  - BACKGROUND: Ocular toxocariasis is usually a unilateral posterior uveitis in
      otherwise asymptomatic children. The authors report the rare occurrence of
      presumed ocular toxocariasis presenting as a juxtapapillary lesion in a 52-year
      old woman with systemic manifestations of visceral larva migrans. CASE REPORT: A
      52-year-old woman presented with blurred vision in her right eye for 2 months.
      She shared her bedroom with two puppies. Best-corrected visual acuity was 20/20
      in both eyes; slit-lamp examination was unremarkable. Funduscopy revealed a
      whitish, elevated, juxtapapillary retinochoroidal lesion of approximately one
      disk diameter size with macular star formation. She also developed severe
      respiratory distress and diarrhea. An intense eosinophilia was detected.
      Investigation included a liver biopsy positive for Toxocara antigens upon
      staining with chromogen 3,3'-diaminobenzidin and anti-Toxocara immunoglobulin G
      >10,240 (enzyme-linked immunosorbent assay). Treatment with albendazole and
      corticosteroids was implemented. Third generation optical coherence tomography
      (Stratus Tomographer, Model 3,000, Carl Zeiss Ophthalmic Systems, Inc., Dublin,
      CA) (OCT) of the macular area was unremarkable, except for a slight increase in
      retinal thickness as it approached the inflammatory lesion. Two months after
      treatment, there was a hypopigmented scar with localized condensed vitreous
      opacities. The OCT demonstrated traction along the vitreoretinal interface as the
      inflammation waned. A conservative approach was maintained as visual acuity
      remained stable. CONCLUSION: OCT imaging may offer a practical means of locating
      and staging posterior pole lesions due to ocular toxocariasis.

PMID- 25390602
TI  - Macular neovascularization in familial exudative vitreoretinopathy.
AB  - PURPOSE: To describe an unusual patient with autosomal dominant familial
      exudative vitreoretinopathy (FEVR) who also presented with preretinal fibrosis
      overlying the macula, extensive macular telangiectasis, and multiple foci of
      macular neovascularization. METHODS: A clinical case is presented including
      fundus images and fluorescein angiography studies of the patient's left eye
      containing the unusual manifestations. RESULTS: To our knowledge, this is the
      first report of the formation of multifocal, preretinal macular
      neovascularization in FEVR. The sites of neovascularization corresponded to the
      attachment points of the vitreous stalk overlying the macula. Two small areas of
      intraretinal neovascularization were also noted. CONCLUSIONS: The concordance of
      the vitreoretinal adhesions with the sites of neovascularization suggests that
      the focal scaffolding may have played a direct mechanical role in encouraging the
      growth of the macular neovascular tissue in this patient.

PMID- 25390603
TI  - Identification of anastomosis between the central retinal artery and the central
      retinal vein in a case of central retinal vein occlusion due to arteriovenous
      malformation.
AB  - PURPOSE: To report the identification of an arteriovenous anastomosis over the
      optic nerve head in a case of arteriovenous malformation. CASE REPORT: Dynamic
      scanning laser angiography was performed in a 12 year old girl with a severe
      arteriovenous malformation complicated by central retinal vein occlusion.
      RESULTS: The presence of an arteriovenous anastomosis between the central retinal
      artery and vein was identified. This anastomosis later regressed completely.
      CONCLUSIONS: An arteriovenous anastomosis between central vessels within the
      optic nerve may be a cause of central retinal vein occlusion. Spontaneous
      regression of the anastomoses may lead to improvement of fundus features.

PMID- 25390604
TI  - Idiopathic juxtapapillary polypoidal choroidal vasculopathy in the papillomacular
      bundle: treatment with photodynamic therapy: two years follow-up.
AB  - PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) in a patient with
      juxtapapillary idiopathic polypoidal choroidal vasculopathy (IPCV) in the
      papillomacular bundle. METHODS: One session of PDT using a spot size with
      diameter of 1000 MUm in the center of the juxtapapillary lesion was applied.
      PATIENT: A 75-year-old woman with decreased vision (20/80) in her right eye over
      a period of 1 year. RESULTS: After a follow-up of 2 years, the best-corrected
      visual acuity was 20/32, the lesion remained sclerosed, and lipids have
      disappeared. CONCLUSION: PDT represented a good treatment for this patient with
      juxtapapillary IPCV.

PMID- 25390605
TI  - Photodynamic therapy directly over the optic nerve head to treat a papillary
      hemangioma.
AB  - PURPOSE: To show how effective photodynamic therapy (PDT) is for papillary
      hemangioma. PATIENT AND METHODS: During follow-up, a papillary hemangioma in a 7
      year-old girl increased in size, reducing visual acuity. PDT (verteporfin at a
      dose of 6 mg/m body surface area and a light dose of 50 J/cm for 83 seconds) with
      a spot placed directly over the whole papilla was used to treat the tumor. A
      reduction in exudation and an improvement in visual acuity were achieved after
      two treatments. DISCUSSION: In this case, PDT over a tumor on the optic nerve
      head allowed preservation of some visual function; this strategy can be
      considered a therapeutic option for tumors in this location.

PMID- 25390606
TI  - Endolymphatic sac tumor as initial manifestation of von hippel-lindau syndrome.
AB  - PURPOSE: To report endolymphatic sac tumor (ELST) as the initial finding in von
      Hippel-Lindau (VHL) syndrome. METHODS: Case report. RESULTS: A 4-year-old boy
      presented in February 2001 with right hearing loss and seventh nerve palsy from
      ELST. Genetic analysis showed a VHL mutation (gene 3p25-26). Systemic and ocular
      examination for VHL syndrome-related tumors was unrevealing. Four years later,
      multiple retinal hemangioblastoma (retinal capillary hemangioma) were detected in
      both eyes and successfully treated with argon laser photocoagulation. CONCLUSION:
      ELSTs can be the initial manifestation of VHL syndrome. Lifelong screening for
      related tumors, particularly retinal hemangioblastoma, is advised.

PMID- 25390607
TI  - Posterior retinal breaks as a cause of vitreous hemorrhage in diabetes.
AB  - PURPOSE: To describe posterior retinal breaks as a cause of vitreous hemorrhage
      in diabetic patients. METHODS: In two institutional practices, six posterior
      retinal breaks were identified in five eyes of five diabetic patients with
      vitreous hemorrhage. All eyes underwent fundus photography and fluorescein
      angiography. Four eyes received barrier photocoagulation. The outcome measures
      included retinal nonperfusion, proximity to retinal vessels, and progression to
      retinal detachment. RESULTS: All six posterior breaks were in areas of retinal
      ischemia. No eyes had neovascularization. Three breaks had a bridging vessel, and
      three were in a paravascular location. One untreated eye had progression to a
      retinal detachment. CONCLUSIONS: The differential diagnosis for vitreous
      hemorrhage in diabetic patients should include posterior retinal breaks,
      particularly in the absence of proliferative disease. These breaks are
      paravascular, are located in areas of retinal ischemia, and may involve avulsed
      bridging vessels. We suggest treatment with barrier rather than panretinal
      photocoagulation.

PMID- 25390608
TI  - Branch retinal artery occlusion after periocular dermal filler injection.
AB  - PURPOSE: To report a case of branch retinal artery occlusion, choroidal ischemia,
      ischemic optic neuropathy, and suspicious traumatic optic neuropathy after
      periocular dermal filler injection. METHODS: History taking and ocular
      examinations were performed to find out the cause of sudden visual loss. RESULTS:
      On the fundus examination, occluded branch retinal artery was filled with long,
      fragmented, transparent materials which might be injected dermal filler.
      Fluorescein angiography showed arterial filling time delay with long, fragmented
      materials obstructing superior temporal retinal artery, nonperfusion areas around
      the occluded retinal artery territory, filling defect at temporal half of optic
      disk, and choroidal filling defect at nasal aspect of the retina. CONCLUSION:
      When injecting dermal filler, ocular complications should be considered.

PMID- 25390609
TI  - Polymicrobial endogenous endophthalmitis.
AB  - PURPOSE: We report a case of polymicrobial endogenous endophthalmitis caused by
      group G streptococcus and Staphylococcus capitis. METHODS: Standard
      ophthalmologic examinations. RESULTS: A 72-year-old woman presented with signs of
      uveitis. Treatment with broad-spectrum antibiotics was prescribed, and vitrectomy
      with intravitreal antibiotic administration was then performed. Blood cultures
      were positive for group G streptococcus and coagulase-negative staphylococcus.
      Cultures of vitreous aspirate yielded group G streptococcus and S. capitis.
      Uveitis was resolved with antibiotic treatment and vitrectomy, with best
      corrected visual acuity of 20/20 at 6 months. CONCLUSIONS: Endogenous
      endophthalmitis can be caused by two intravitreal organisms (e.g., group G
      streptococcus and S. capitis). Early treatment with broad-spectrum antibiotics
      and vitrectomy with intravitreal injections of antibiotic might be considered in
      similar cases.

PMID- 25390610
TI  - Diffuse unilateral subacute neuroretinitis: a case of mistaken identity.
AB  - BACKGROUND: The report details a case of diffuse unilateral subacute
      neuroretinitis (DUSN) wherein a subretinal parasite was visualized and
      subsequently destroyed with laser photocoagulation. METHODS: Full historical and
      serologic investigations were carried out. A literature search to determine all
      possible causes of DUSN was also completed. RESULTS: Serologic results supported
      Baylisascaris procyonis as the cause of infection, but imaging of the worm before
      destruction did not support this organism as the etiologic agent. On the basis of
      morphologic evaluation of still imaging and videoimaging, patient exposure
      information, and known causes of DUSN, the infection was likely due to Alaria
      species, providing further evidence of a trematode cause. CONCLUSIONS: The report
      adds to the literature that trematodes should be recognized as a possible cause
      of ocular larva migrans. Although laser therapy is appropriate and effective for
      both nematode and trematode infections of the eye, in the case of adjunctive
      medical therapy, identification of the parasite group is essential.

PMID- 25390611
TI  - Anorectal melanoma: an uncommon and aggressive disease.

PMID- 25390612
TI  - Missed opportunities for prevention of perinatal transmission of hepatitis B: a
      retrospective cohort study.
AB  - BACKGROUND: Perinatal transmission of hepatitis B virus (HBV) can occur despite
      postexposure prophylaxis (PEP). Recent literature suggests that antiviral
      treatment during pregnancy when maternal HBV DNA levels are elevated can further
      decrease vertical transmission. However, HBV DNA screening is not routinely
      performed antenatally. OBJECTIVE: To determine the rates of HBV prevalence and
      perinatal transmission in an antenatal cohort. METHODS: A retrospective review of
      public health records (December 2008 to December 2010) was performed for both
      mothers and newborns. RESULTS: A total of 725 mother-infant pairs were included.
      Of these, 574 of 715 (80%) women had antenatal hepatitis B e antigen (HBeAg)
      testing performed, and 127 of 574 (22%) were HBeAg positive (HBeAg+). Of babies
      born to hepatitis B surface antigen-positive (HBsAg+) mothers, only 573 of 725
      (79%) received complete PEP. In addition, 172 of 725 (24%) infants did not
      receive post-PEP blood testing or were lost to follow-up. Of the 552 infants with
      results available, seven cases (1.3%) of mother-to-child HBV transmission were
      observed, six of which involved infants born to HBeAg+ women. CONCLUSIONS: Our
      findings suggest that routine HBeAg screening could identify a subset of mother
      infant pairs among HBsAg+ pregnant women who are at higher risk for vertical HBV
      transmission. Determination of viral load in expectant HBeAg+ mothers may provide
      more precise insight into HBV transmission to their infants.

PMID- 25390613
TI  - Transitioning to highly effective therapies for the treatment of chronic
      hepatitis C virus infection: a policy statement and implementation guideline.
AB  - Chronic hepatitis C virus (HCV) infection increases all-cause mortality, rates of
      cirrhosis, hepatocellular carcinoma, liver transplantation and overall health
      care utilization. Morbidity and mortality disproportionately affect individuals
      born between 1945 and 1975. The recent development of well-tolerated and highly
      effective therapies for chronic HCV infection represents a unique opportunity to
      dramatically reduce rates of HCV-related complications and their costs. Critical
      to the introduction of such therapies will be well-designed provincial
      programming to ensure immediate treatment access to individuals at highest risk
      for complication, and well-defined strategies to address the global treatment
      needs of traditionally high-risk and marginalized populations. HCV practitioners
      in New Brunswick created a provincial strategy that stratifies treatment
      according to those at highest need, measures clinical impact, and creates
      evaluation strategies to demonstrate the significant direct and indirect cost
      savings anticipated with curative treatments. 

PMID- 25390614
TI  - Are patient-reported outcome measures the way to go in inflammatory bowel
      disease?

PMID- 25390616
TI  - Timing of rebleeding in high-risk peptic ulcer bleeding after successful
      hemostasis: a systematic review.
AB  - BACKGROUND: Peptic ulcer rebleeding (PUR) usually occurs within three days
      following endoscopic hemostasis. However, recent data have increasingly suggested
      delayed rebleeding. ? OBJECTIVE: To better characterize the timing of PUR
      (Forrest Ia to IIb) following initially successful endoscopic hemostasis. ?
      METHODS: An exhaustive literature search (1989 to 2013), with cross-referencing,
      was performed to identify pertinent randomized controlled trial (RCT) arms.
      Patients receiving high-dose proton pump inhibitor (PPI) infusion following
      successful modern-day endoscopic hemostasis were included. A sensitivity analysis
      included any patients receiving PPI doses >40 mg daily. The main outcome measure
      was 30-day rebleeding, while weighted mean averages at t = three, seven, 14 and
      28 to 30 days are also reported. RESULTS: Of 756 citations, six RCTs were
      included (561 patients; 58.5% to 89.5% male; 55.3 to 67.5 years of age). Among
      patients receiving high-dose PPI (five RCTs [393 patients]), 11.5% (95% CI 8.4%
      to 14.7%) experienced rebleeding, 55.6% (95% CI 41.1% to 70.1%) rebled within
      three days, 20% (95% CI 8.3% to 31.7%) between four and seven days, 17.8% (95% CI
      6.6% to 28.9%) at eight to 14 days, and 6.7% (95% CI 0% to 14%) at 15 to 28 to 30
      days. Using the relaxed lower PPI dosing threshold, similar respective rates were
      14.4% (95% CI 11.5% to 17.3%) overall, with interval rates of 39.5% (95% CI 28.9%
      to 50.15%), 34.6% (95% CI 24.2% to 44.9%), 19.7% (95% CI 11% to 28.4%) and 6.2%
      (95% CI 0.95% to 11.5%). Qualitative review of patient characteristics, limited
      by small sample size, possible bias and study heterogeneity, suggested increased
      patient comorbidity and postendoscopic use of lower PPI dosing may predict
      delayed rebleeding. ? CONCLUSION: In patients with high-risk PUR undergoing
      successful endoscopic hemostasis, most rebled within three days, with many
      experiencing later rebleeding. Additional research is needed to better predict
      such an outcome.

PMID- 25390615
TI  - Patient-reported outcome measures in inflammatory bowel disease.
AB  - Patient-reported outcome measures (PROMs) are increasingly used in both research
      and clinical health settings. With the recent development of United States Food
      and Drug Administration guidance on PROMs, more attention is being devoted to
      their role and importance in health care. Several methodological challenges in
      the development, validation and implementation of PROMs must be resolved to
      ensure their appropriate utilization and interpretation. The present review
      discusses recent developments and updates in PROMs, with specific focus on the
      area of inflammatory bowel disease. 

PMID- 25390619
TI  - Design and synthesis of donor-acceptor Stenhouse adducts: a visible light
      photoswitch derived from furfural.
AB  - The development of an easily synthesized, modular, and tunable organic
      photoswitch that responds to visible light has been a long-standing pursuit.
      Herein we provide a detailed account of the design and synthesis of a new class
      of photochromes based on furfural, termed donor-acceptor Stenhouse adducts
      (DASAs). A wide variety of these derivatives are easily prepared from
      commercially available starting materials, and their photophysical properties are
      shown to be dependent on the substituents of the push-pull system. Analysis of
      the switching behavior provides conditions to access the two structural isomers
      of the DASAs, reversibly switch between them, and use their unique solubility
      behavior to provide dynamic phase-transfer materials. Overall, these negative
      photochromes respond to visible light and heat and display an unprecedented level
      of structural modularity and tunabilty. 

PMID- 25390617
TI  - Systematic review of stimulant and nonstimulant laxatives for the treatment of
      functional constipation.
AB  - BACKGROUND: Constipation is an uncomfortable and common condition that affects
      many, irrespective of age. Since 1500 BC and before, health care practitioners
      have provided treatments and prevention strategies to patients for chronic
      constipation despite the significant variation in both medical and personal
      perceptions of the condition. OBJECTIVE: To review relevant research evidence
      from clinical studies investigating the efficacy and safety of commercially
      available pharmacological laxatives in Canada, with emphasis on studies adopting
      the Rome criteria for defining functional constipation. SEARCH METHODS: PubMed,
      Medline, Embase and Evidence-Based Medicine Reviews databases were searched for
      blinded or randomized clinical trials and meta-analyses assessing the efficacy of
      nonstimulant and stimulant laxatives for the treatment of functional
      constipation. RESULTS: A total of 19 clinical studies and four meta-analyses were
      retrieved and abstracted regarding study design, participants, interventions and
      outcomes. The majority of studies focused on polyethylene glycol compared with
      placebo. Both nonstimulant and stimulant laxatives provided better relief of
      constipation symptoms than placebo according to both objective and subjective
      measures. Only one study compared the efficacy of a nonstimulant versus a
      stimulant laxative, while only two reported changes in quality of life. All
      studies reported minor side effects due to laxative use, regardless of treatment
      duration, which ranged from one week to one year. Laxatives were well tolerated
      by both adults and children.

PMID- 25390620
TI  - Demand for modern family planning among married women living with HIV in western
      Ethiopia.
AB  - INTRODUCTION: People living with HIV (PLHIV) have diverse family planning (FP)
      needs. Little is reported on FP needs among women living with HIV in Ethiopia.
      Thus, the objective of the study was to assess the demand for modern FP among
      married women living with HIV in western Ethiopia. METHODS: A facility-based
      cross-sectional survey was conducted on 401 married women living with HIV
      selected from Nekemte Referral Hospital and Health Center, Nekemte, Oromia,
      Ethiopia. Convenience sampling of every other eligible patient was used to
      recruit respondents. Data were collected using a pretested, structured
      questionnaire. We first calculated frequency and percentage of unmet need, met
      need and total demand by each explanatory variable, and performed chi-squared
      testing to assess for differences in groups. We then fitted logistic regression
      models to identify correlates of unmet need for modern FP at 95% CL. RESULTS: The
      proportion of respondents with met need for modern FP among married women living
      with HIV was 61.6% (30.7% for spacing and 30.9% for limiting). Demand for family
      planning was reported in 77.0% (38.2% for spacing and 38.8% for limiting), making
      unmet need for modern FP prevalent in 15.4% (7.5% for spacing and 7.9% for
      limiting). Whereas age 25-34 years [adjusted odds ratio (AOR) (95% confidence
      interval (CI)) = .397 (.204-.771)] was protective against unmet need for modern
      FP, not having knowledge of MTCT [AOR (95% CI) = 2.531 (1.689-9.290)] and not
      discussing FP with a partner [AOR (95% CI) = 3.616(1.869-6.996)] were associated
      with increased odds of unmet need for modern FP. CONCLUSIONS: There is high unmet
      need for modern FP in HIV-positive married women in western Ethiopia. Health care
      providers and program managers at a local and international level should work to
      satisfy the unmet need for modern family planning.

PMID- 25390622
TI  - In vivo imaging of miliaria profunda using high-definition optical coherence
      tomography: diagnosis, pathogenesis, and treatment.

PMID- 25390621
TI  - Mitochondrial DNA (mtDNA) haplogroups influence the progression of knee
      osteoarthritis. Data from the Osteoarthritis Initiative (OAI).
AB  - OBJECTIVE: To evaluate the influence of the mtDNA haplogroups on knee
      osteoarthritis progression in Osteoarthritis Initiative (OAI) participants
      through longitudinal data from radiographs and magnetic resonance imaging (MRI).
      METHODS: Four-year knee osteoarthritis progression was analyzed as increase in
      Kellgren and Lawrence (KL) grade, in addition to increase in OARSI atlas grade
      for joint space narrowing (JSN), osteophytes and subchondral sclerosis in the
      tibia medial compartment of 891 Caucasian individuals from the progression
      subcohort. The influence of the haplogroups on the rate of structural progression
      was also assessed as the four-year change in minimum joint space width (mJSW in
      millimetres) in both knees of (n = 216) patients with baseline unilateral medial
      tibiofemoral JSN. Quantitative cartilage measures from longitudinal MRI data were
      those related to cartilage thickness and volume with a 24 month follow-up period
      (n = 381). RESULTS: During the four-year follow-up period, knee OA patients with
      the haplogroup T showed the lowest increase in KL grade (Hazard Risk [HR] =
      0.499; 95% Confidence Interval [CI]: 0.261-0.819; p<0.05) as well as the lowest
      cumulative probability of progression for JSN (HR = 0.547; 95% CI: 0.280-0.900;
      p<0.05), osteophytes (HR = 0.573; 95% CI: 0.304-0.893; p<0.05) and subchondral
      sclerosis (HR = 0.549; 95% CI: 0.295-0.884; p<0.05). They also showed the lowest
      decline in mJSW (standardized response means (SRM) = -0.39; p = 0.037) in those
      knees without baseline medial JSN (no-JSN knees). Normalized cartilage volume
      loss was significantly lower in patients carrying the haplogroup T at medial
      tibia femoral (SRM = -0.33; p = 0.023) and central medial femoral (SRM = -0.27; p
      = 0.031) compartments. Cartilage thickness loss was significantly lower in
      carriers of haplogroup T at central medial tibia-femoral (SRM = -0.42; p =
      0.011), medial tibia femoral (SRM = -0.32; p = 0.018), medial tibia anterior (SRM
      = +0.31; p = 0.013) and central medial femoral (SRM = -0.19; p = 0.013)
      compartments. CONCLUSIONS: Mitochondrial genome seems to play a role in the
      progression of knee osteoarthritis. mtDNA variation could improve identification
      of patients predisposed to faster or severe progression of the disease.

PMID- 25390623
TI  - All-atom CHARMM force field and bulk properties of perfluorozinc phthalocyanines.
AB  - Classical force fields within the CHARMM parametrized model are developed for
      zinc phthalocyanines including the parent per-hydro molecule and per-fluoro-alkyl
      substituted derivatives. Partial atomic charges, 2-body bond lengths, and 3-body
      angle parameters were obtained from B3LYP-level density functional calculations.
      Force constants for 2-, 3-, and 4-body interactions were derived from existing
      fluoroalkane models and incorporated assuming transferability. The force fields
      were validated by comparing equilibrium molecular geometries from molecular
      dynamics simulations with density functional theory (DFT) calculations and, where
      available, published experimental XRD refinements. The models produce molecular
      geometries for the target materials within 1-2% of expected values.
      Intermolecular interaction geometries were also investigated using molecular
      dynamics simulations. The results provide new insight and predictions of the
      equilibrium stacking and orientational intermolecular interactions of this novel
      class of modified phthalocyanines. 

PMID- 25390624
TI  - [Asthma: how does mepolizumab affect exacerbations and need for steroids?
      Mepolizumab is a new therapeutic option in severe asthma [corrected]].

PMID- 25390625
TI  - [Cardiovascular risk factors and their influence on the physical fitness of young
      adults: an assessment among regular and professional soldiers in Germany].
AB  - BACKGROUND AND AIMS: The physical, mental and cognitive demands for military
      servicemen and -women have increased over the last decades. On the other side,
      modern society has become a service society with low physical activity during
      daily life. Consequently, knowledge about effects of this unfavorable lifestyle
      for physical fitness is of high concern. PATIENTS AND METHODS: A retrospective
      cross-sectional study was done that included 1570 active soldiers (95.3% men;
      mean age 23.8 +/- 2.7 years). Number of cardiovascular risk factors, their
      influence on physical fitness and reasons for non-fitness for a soldier career
      were recorded methodically. RESULTS: 54.8% of the examined soldiers were active
      smokers, 51.1% were overweight or obese and 22.6% had a positive family history
      of cardiovascular diseases. Lipometabolic disorder was lower (14.9 and 21.2%,
      respectively ) and apparent diseases were rarely or not detectable. Physical
      fitness on a bicycle ergometer decreased with increasing number of cardiovascular
      risk factors. Overweight and hypercholesterolemia were the risk factors with the
      greatest effect on this reduction. The most frequent reasons for non-fitness for
      duty were overweight, nutritive-toxic liver diseases and low physical fitness.
      CONCLUSION: The reduction of physical fitness due to the increasing number of
      cardiovascular risk factors is a serious problem, particularly because it happens
      in absence of manifest chronic diseases.

PMID- 25390626
TI  - [Bilateral facial palsy following pulmonary infection--a possible variant of
      acute inflammatory polyradiculoneuropathy].
AB  - HISTORY AND CLINICAL FINDINGS: A 43-year old female presented with bilateral
      facial muscle weakness a month after onset of upper respiratory tract infection.
      INVESTIGATIONS: The neurologic examination on admission revealed bilateral facial
      palsy, no signs of muscular weakness, hyperreflexia and flexor plantar responses.
      Extensive laboratory analysis, radiological and neuroimaging assessment were
      unremarkable but analysis of cerebrospinal fluid revealed albumin-cytological
      dissociation. Sequentially, nerve conduction studies confirmed demyelination of
      both facial nerves. A diagnosis of Guillain-Barre syndrome was made according to
      clinical findings, laboratory results and nerve study results. TREATMENT AND
      COURSE: IVIg therapy was initiated (2 g/kg per 5 days) after no response to
      tapered intravenous corticosteroid therapy. Five days after the last IVIg dose
      the patient started to recover. Both eyes were treated with standard protective
      measures. CONCLUSION: Guillain-Barre syndrome is an acute autoimmune
      polyneuropathy characterized by a course of rapid ascending muscular weakness and
      mild sensory symptoms appearing approximately two-four weeks after an infection.
      The facial nerve is of all cranial nerves most often affected but it is rarely
      the prominent sign of GBS. As well, bilateral facial palsy has never been
      described as a sole manifestation of GBS, as of our notion.

PMID- 25390627
TI  - [Poor medication adherence and worsening of heart failure--a vicious circle].
AB  - Despite of markedly improved options for treatment, chronic heart failure is
      associated with recurrent worsening of symptoms. Poor medication adherence has
      adverse effects on frequency and progression of congestive heart failure. There
      are three relevant areas of problems that could be aggravated by each other:There
      is the problem of changes in pharmacokinetics in worsening heart failure.
      Proportional to the severity of heart failure, there is an existing intestinal
      edema and changes of intestinal bacterial colonization that may affect a drug's
      absorption and, hence, its efficacy.Depression and impaired cognitive function is
      quite common in patients with chronic heart failure. Depression both predicts
      hospitalization and mortality rate as well as poor medication adherence in CHF.
      Compared to stable CHF patients, cognitive function deteriorates significantly
      while decompensation leading to impaired medication adherence.Shown by recent
      studies, there is a higher risk for poor medication adherence after a
      cardiovascular event.Poor medication adherence is associated with an increased
      rate of cardiovascular events not only in heart failure, but also in all
      cardiovascular diseases. Hence, there is a need for specific and long term
      interventions to improve medication adherence at an early stage. 

PMID- 25390628
TI  - [23-year-old woman with general weakness and iron deficiency].

PMID- 25390629
TI  - [Evolution of biologicals in inflammation medicine--biosimilars in
      gastroenterology, rheumatology and dermatology].
AB  - Biologicals revolutionized the therapy of chronic inflammatory diseases in
      gastroenterology, rheumatology and dermatology in the last decade. The first
      generation biologicals mainly targeted against the pro-inflammatory cytokine TNF
      alpha. The evolution of these therapies in the last years led to the development
      of new antibodies and to the admission of first generation "generic" biologics -
      the biosimilars. Biosimilars are not a fundamental new pharmacological
      development for existing substances, however they have the potential to lead to
      enormous cost savings in healthcare without reducing the level of care for
      patients. Biosimilars are not identical with the originator, but in an extensive
      biosimilarity exercise including analytical, preclinical and comparative clinical
      studies it was shown that the biosimilars could demonstrate comparability in all
      relevant aspects with the originator.In September 2013, the Infliximab
      biosimilars (Inflectra((r)), Remsina((r))) were the first biosimilars for
      monoclonal antibodies to be authorized by the EMA for use in the European Union.
      By demonstrating the therapeutic similarity only in one indication (rheumatoid
      arthritis) the EMA agreed with an extrapolation also to all approved indications
      of the originator. This could be a relevant problem in clinical practice.
      Therefore, comparative studies with the originator are required in all approved
      indications.After expiration of the national patent protection in beginning of
      2015, the infliximab biosimilars will be launched on the market in Germany and
      will be part of the therapeutic arsenal in gastroenterology, rheumatology and
      dermatology. Interchangeability (Switching) of biosimilars with the originator
      will be subject of an important discussion with the health care providers.
      Regardless of the biosimilars EMA-approval, several potential problems (efficacy,
      extrapolation, switching, long-term safety) should be the topic of intensive long
      term registries in the future. 

PMID- 25390630
TI  - [HPV induced condylomas, carcinomas and precursor lesions--an interdisciplinary
      challenge].

PMID- 25390631
TI  - [All-oral, interferon-free therapies for patients with chronic genotype 1
      hepatitis C virus infection].

PMID- 25390632
TI  - [Death--a troubleshooter? An ethical criticism of assisted suicide].

PMID- 25390634
TI  - Quasi-linear vacancy dynamics modeling and circuit analysis of the bipolar
      memristor.
AB  - The quasi-linear transport equation is investigated for modeling the bipolar
      memory resistor. The solution accommodates vacancy and circuit level perspectives
      on memristance. For the first time in literature the component resistors that
      constitute the contemporary dual variable resistor circuit model are quantified
      using vacancy parameters and derived from a governing partial differential
      equation. The model describes known memristor dynamics even as it generates new
      insight about vacancy migration, bottlenecks to switching speed and elucidates
      subtle relationships between switching resistance range and device parameters.
      The model is shown to comply with Chua's generalized equations for the memristor.
      Independent experimental results are used throughout, to validate the insights
      obtained from the model. The paper concludes by implementing a memristor
      capacitor filter and compares its performance to a reference resistor-capacitor
      filter to demonstrate that the model is usable for practical circuit analysis. 

PMID- 25390633
TI  - High-frequency rugose exopolysaccharide production by Vibrio cholerae strains
      isolated in Haiti.
AB  - In October, 2010, epidemic cholera was reported for the first time in Haiti in
      over 100 years. Establishment of cholera endemicity in Haiti will be dependent in
      large part on the continued presence of toxigenic V. cholerae O1 in aquatic
      reservoirs. The rugose phenotype of V. cholerae, characterized by
      exopolysaccharide production that confers resistance to environmental stress, is
      a potential contributor to environmental persistence. Using a microbiologic
      medium promoting high-frequency conversion of smooth to rugose (S-R) phenotype,
      80 (46.5%) of 172 V. cholerae strains isolated from clinical and environmental
      sources in Haiti were able to convert to a rugose phenotype. Toxigenic V.
      cholerae O1 strains isolated at the beginning of the epidemic (2010) were
      significantly less likely to shift to a rugose phenotype than clinical strains
      isolated in 2012/2013, or environmental strains. Frequency of rugose conversion
      was influenced by incubation temperature and time. Appearance of the biofilm
      produced by a Haitian clinical rugose strain (altered biotype El Tor HC16R)
      differed from that of a typical El Tor rugose strain (N16961R) by confocal
      microscopy. On whole-genome SNP analysis, there was no phylogenetic clustering of
      strains showing an ability to shift to a rugose phenotype. Our data confirm the
      ability of Haitian clinical (and environmental) strains to shift to a protective
      rugose phenotype, and suggest that factors such as temperature influence the
      frequency of transition to this phenotype. 

PMID- 25390635
TI  - Ensemble-based network aggregation improves the accuracy of gene network
      reconstruction.
AB  - Reverse engineering approaches to constructing gene regulatory networks (GRNs)
      based on genome-wide mRNA expression data have led to significant biological
      findings, such as the discovery of novel drug targets. However, the reliability
      of the reconstructed GRNs needs to be improved. Here, we propose an ensemble
      based network aggregation approach to improving the accuracy of network
      topologies constructed from mRNA expression data. To evaluate the performances of
      different approaches, we created dozens of simulated networks from combinations
      of gene-set sizes and sample sizes and also tested our methods on three
      Escherichia coli datasets. We demonstrate that the ensemble-based network
      aggregation approach can be used to effectively integrate GRNs constructed from
      different studies - producing more accurate networks. We also apply this approach
      to building a network from epithelial mesenchymal transition (EMT) signature
      microarray data and identify hub genes that might be potential drug targets. The
      R code used to perform all of the analyses is available in an R package entitled
      "ENA", accessible on CRAN (http://cran.r-project.org/web/packages/ENA/). 

PMID- 25390636
TI  - Inflammation-induced reactivation of the ranavirus Frog Virus 3 in asymptomatic
      Xenopus laevis.
AB  - Natural infections of ectothermic vertebrates by ranaviruses (RV, family
      Iridoviridae) are rapidly increasing, with an alarming expansion of RV tropism
      and resulting die-offs of numerous animal populations. Notably, infection studies
      of the amphibian Xenopus laevis with the ranavirus Frog Virus 3 (FV3) have
      revealed that although the adult frog immune system is efficient at controlling
      RV infections, residual quiescent virus can be detected in mononuclear phagocytes
      of otherwise asymptomatic animals following the resolution of RV infections. It
      is noteworthy that macrophage-lineage cells are now believed to be a critical
      element in the RV infection strategy. In the present work, we report that
      inflammation induced by peritoneal injection of heat-killed bacteria in
      asymptomatic frogs one month after infection with FV3 resulted in viral
      reactivation including detectable viral DNA and viral gene expression in
      otherwise asymptomatic frogs. FV3 reactivation was most prominently detected in
      kidneys and in peritoneal HAM56+ mononuclear phagocytes. Notably, unlike adult
      frogs that typically clear primary FV3 infections, a proportion of the animals
      succumbed to the reactivated FV3 infection, indicating that previous exposure
      does not provide protection against subsequent reactivation in these animals. 

PMID- 25390637
TI  - Vancomycin dosing in neutropenic patients.
AB  - BACKGROUND: To compare vancomycin pharmacokinetic parameters in patients with and
      without neutropenia. METHODS: Patients >=18 years admitted on general wards were
      included. Routinely vancomycin trough and peak plasma concentrations were
      measured with a fluorescence polarization immunoassay. Pharmacokinetic parameters
      of individual patients were determined with maximum a posterior Bayesian
      estimation (MW Pharm 3.60). Neutropenia was defined as neutrophils <0.5*109
      cells/L. PRINCIPAL FINDINGS: A total of 171 patients were included. Patients with
      neutropenia (n = 56) had higher clearance of vancomycin (CLva), 67 (+/-26)
      mL/min, compared to patients without neutropenia (n = 115), CLva 50 (+/-22)
      mL/min (p<0.001). No significant difference was found in serum creatinine and
      vancomycin volume of distribution. Neutropenia was positively associated with
      CLva, independently of relevant co-variables (B: 12.122, 95%CI: 1.095 to 23.149,
      p = 0.031). On average patients with neutropenia needed 33% higher doses of
      vancomycin to attain adequate exposure, i.e. AUC24>=400 mg*h/L. Furthermore, 15
      initially neutropenic patients in our study group received vancomycin for a
      second administration period. Ten patients received the second administration
      period during another neutropenic period and 5 patients during a non-neutropenic
      phase. All 5 patients with vancomycin during both neutropenic and non-neutropenic
      phase had higher CLva (91 (+/-26) mL/min) during the neutropenic period and lower
      CLva (45 (+/-10) mL/min) during the non-neutropenic phase (p = 0.009).
      CONCLUSION: This study shows that most patients with neutropenia have augmented
      CLva. In a small group of patients that received vancomycin during two episodes,
      the augmented CLva seems to be reversible in the non-neutropenic period. Our data
      indicate that it is important to increase the daily dose with one third in
      patients with neutropenia (from 15 mg/kg twice daily to 13 mg/kg three times
      daily). Frequent performance of therapeutic drug monitoring in patients with
      neutropenia may prevent both therapy failure due to low AUCs and overcomes
      toxicity due to high vancomycin trough concentrations during recovery from
      neutropenia.

PMID- 25390638
TI  - Upper tract juvenile polyps in juvenile polyposis patients: dysplasia and
      malignancy are associated with foveolar, intestinal, and pyloric differentiation.
AB  - Patients with juvenile polyposis syndrome (JPS), a hereditary autosomal dominant
      hamartomatous polyposis syndrome, are at increased risk for colorectal
      adenocarcinoma. The upper gastrointestinal tract is less often involved by JPS
      than the colorectum, and, consequently, upper tract juvenile polyps (JPs) are not
      well studied. We reviewed upper endoscopies and corresponding biopsies in JPS
      patients documented in our Polyposis Registry. A total of 199 upper
      gastrointestinal biopsies from 69 endoscopies were available in 22 of 41 (54%)
      JPS patients. Thirteen of the 22 patients (59%) had >=1 gastric JP; 5 also had 6
      small bowel JPs. Gastric JP was identified as early as age 7 in a patient with an
      SMAD4 gene mutation. Two patients (9%) had high-grade dysplasia in gastric JP.
      Invasive adenocarcinoma was diagnosed in the gastrectomy specimen of 1 patient.
      Five patients had a huge gastric polyp burden; 3 underwent total gastrectomy.
      Three patients died of complications associated with extensive upper JP.
      Histologically, 8 of the 56 (14%) gastric JPs identified had dysplasia. All of
      the 8 polyps demonstrated intestinalized and pyloric gland differentiation
      intermixed with foveolar epithelium. Dysplasia was seen arising in all 3 types of
      epithelium. The flat gastric mucosa in 11 patients was unremarkable without
      inflammation or intestinal metaplasia. The 6 small bowel JPs had no dysplasia.
      Our findings suggest that JPS patients are at increased risk for gastric
      adenocarcinoma. Detection of malignancy in syndromic gastric JP indicates that
      the current screening procedures are insufficient in removal of precursor lesions
      to prevent progression to carcinoma. 

PMID- 25390639
TI  - Molecular epidemiology of seal parvovirus, 1988-2014.
AB  - A novel parvovirus was discovered recently in the brain of a harbor seal (Phoca
      vitulina) with chronic meningo-encephalitis. Phylogenetic analysis of this virus
      indicated that it belongs to the genus Erythroparvovirus, to which also human
      parvovirus B19 belongs. In the present study, the prevalence, genetic diversity
      and clinical relevance of seal parvovirus (SePV) infections was evaluated in both
      harbor and grey seals (Halichoerus grypus) that lived in Northwestern European
      coastal waters from 1988 to 2014. To this end, serum and tissue samples collected
      from seals were tested for the presence of seal parvovirus DNA by real-time PCR
      and the sequences of the partial NS gene and the complete VP2 gene of positive
      samples were determined. Seal parvovirus DNA was detected in nine (8%) of the
      spleen tissues tested and in one (0.5%) of the serum samples tested, including
      samples collected from seals that died in 1988. Sequence analysis of the partial
      NS and complete VP2 genes of nine SePV revealed multiple sites with nucleotide
      substitutions but only one amino acid change in the VP2 gene. Estimated
      nucleotide substitution rates per year were 2.00 * 10(-4) for the partial NS gene
      and 1.15 * 10(-4) for the complete VP2 gene. Most samples containing SePV DNA
      were co-infected with phocine herpesvirus 1 or PDV, so no conclusions could be
      drawn about the clinical impact of SePV infection alone. The present study is one
      of the few in which the mutation rates of parvoviruses were evaluated over a
      period of more than 20 years, especially in a wildlife population, providing
      additional insights into the genetic diversity of parvoviruses.

PMID- 25390640
TI  - Preliminary investigation into a potential role for myostatin and its receptor
      (ActRIIB) in lean and obese horses and ponies.
AB  - Obesity is a widespread problem across the leisure population of horses and
      ponies in industrialised nations. Skeletal muscle is a major contributor to whole
      body resting energy requirements and communicates with other tissues through the
      secretion of myokines into the circulation. Myostatin, a myokine and negative
      regulator of skeletal muscle mass, has been implicated in obesity development in
      other species. This study evaluated gene and protein expression of myostatin and
      its receptor, ActRIIB in adipose tissues and skeletal muscles and serum myostatin
      concentrations in six lean and six obese animals to explore putative associations
      between these factors and obesity in horses and ponies. Myostatin mRNA expression
      was increased while ActRIIB mRNA was decreased in skeletal muscles of obese
      animals but these differences were absent at the protein level. Myostatin mRNA
      was increased in crest fat of obese animals but neither myostatin nor ActRIIB
      proteins were detected in this tissue. Mean circulating myostatin concentrations
      were significantly higher in obese than in lean groups; 4.98 ng/ml (+/-2.71) and
      9.00 ng/ml (+/-2.04) for the lean and obese groups, respectively. In addition,
      there was a significant positive association between these levels and myostatin
      gene expression in skeletal muscles (average R2 = 0.58; p<0.05). Together, these
      results provide further basis for the speculation that myostatin and its receptor
      may play a role in obesity in horses and ponies. 

PMID- 25390641
TI  - Revisiting robustness and evolvability: evolution in weighted genotype spaces.
AB  - Robustness and evolvability are highly intertwined properties of biological
      systems. The relationship between these properties determines how biological
      systems are able to withstand mutations and show variation in response to them.
      Computational studies have explored the relationship between these two properties
      using neutral networks of RNA sequences (genotype) and their secondary structures
      (phenotype) as a model system. However, these studies have assumed every mutation
      to a sequence to be equally likely; the differences in the likelihood of the
      occurrence of various mutations, and the consequence of probabilistic nature of
      the mutations in such a system have previously been ignored. Associating
      probabilities to mutations essentially results in the weighting of genotype
      space. We here perform a comparative analysis of weighted and unweighted neutral
      networks of RNA sequences, and subsequently explore the relationship between
      robustness and evolvability. We show that assuming an equal likelihood for all
      mutations (as in an unweighted network), underestimates robustness and
      overestimates evolvability of a system. In spite of discarding this assumption,
      we observe that a negative correlation between sequence (genotype) robustness and
      sequence evolvability persists, and also that structure (phenotype) robustness
      promotes structure evolvability, as observed in earlier studies using unweighted
      networks. We also study the effects of base composition bias on robustness and
      evolvability. Particularly, we explore the association between robustness and
      evolvability in a sequence space that is AU-rich-sequences with an AU content of
      80% or higher, compared to a normal (unbiased) sequence space. We find that
      evolvability of both sequences and structures in an AU-rich space is lesser
      compared to the normal space, and robustness higher. We also observe that AU-rich
      populations evolving on neutral networks of phenotypes, can access less
      phenotypic variation compared to normal populations evolving on neutral networks.

PMID- 25390642
TI  - Viscosity of Nafion oligomers as a function of hydration and counterion type: a
      molecular dynamics study.
AB  - The design of fuel cells and lithium ion batteries is constrained, in part, by
      mechanical creep and perforation of the polymer electrolyte, a process that is
      poorly understood at the molecular level. The mechanical stiffness (quantified as
      shear viscosity) and structure of a widely used polymer electrolyte, Nafion, are
      studied in the limit of a low solvent volume fraction (<=26% v/v H2O) using
      molecular dynamics simulations. The viscosity is shown to increase by up to 4
      orders of magnitude in response to changes in composition representing as little
      as 2 wt % of system. Two types of compositional changes are considered, changes
      in solvent volume fraction and counterion type. A system with a counterion X(v+)
      for every v Nafion monomers and y water molecules is denoted as (RSO3)vX.(H2O)y.
      The following trend is observed in viscosity: (RSO3)2Ca > RSO3Na > RSO3H.(H2O)3 >
      RSO3H ~ RSO3H.(H2O)10. This trend correlates with changes in the strength of the
      SO3(-)/X(v+)/SO3(-) cross-links and the size of the cross-link networks.
      Counterion type is shown to strongly influence the morphology. The simulations
      are able to reproduce some important experimental trends without crystalline
      domains or high-MW effects like entanglements, providing a simplified
      understanding of the mechanical properties of Nafion. 

PMID- 25390643
TI  - Research development on sodium-ion batteries.

PMID- 25390644
TI  - Investigation of adhesion and mechanical properties of human glioma cells by
      single cell force spectroscopy and atomic force microscopy.
AB  - Active cell migration and invasion is a peculiar feature of glioma that makes
      this tumor able to rapidly infiltrate into the surrounding brain tissue. In our
      recent work, we identified a novel class of glioma-associated-stem cells (defined
      as GASC for high-grade glioma--HG--and Gasc for low-grade glioma--LG) that,
      although not tumorigenic, act supporting the biological aggressiveness of glioma
      initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their
      motility. Migrating cancer cells undergo considerable molecular and cellular
      changes by remodeling their cytoskeleton and cell interactions with surrounding
      environment. To get a better understanding about the role of the glioma
      associated-stem cells in tumor progression, cell deformability and interactions
      between glioma-initiating stem cells and glioma-associated-stem cells were
      investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem
      cells was studied by time-lapse microscopy, while cell deformability and cell
      cell adhesion strengths were quantified by indentation measurements by atomic
      force microscopy and single cell force spectroscopy. Our results demonstrate that
      for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma
      associated-stem cells, in agreement with their neoplastic features. The adhesion
      strength of GSC on GASC appears to be significantly lower than that observed for
      Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion
      strength increased as compared to that obtained on GASC. These findings highlight
      that the grade of glioma-associated-stem cells plays an important role in
      modulating cancer cell adhesion, which could affect glioma cell migration,
      invasion and thus cancer aggressiveness. Moreover this work provides evidence
      about the importance of investigating cell adhesion and elasticity for new
      developments in disease diagnostics and therapeutics.

PMID- 25390645
TI  - Genome-wide and gene-based association studies of anxiety disorders in European
      and African American samples.
AB  - Anxiety disorders (ADs) are common mental disorders caused by a combination of
      genetic and environmental factors. Since ADs are highly comorbid with each other,
      partially due to shared genetic basis, studying AD phenotypes in a coordinated
      manner may be a powerful strategy for identifying potential genetic loci for ADs.
      To detect these loci, we performed genome-wide association studies (GWAS) of ADs.
      In addition, as a complementary approach to single-locus analysis, we also
      conducted gene- and pathway-based analyses. GWAS data were derived from the
      control sample of the Molecular Genetics of Schizophrenia (MGS) project (2,540
      European American and 849 African American subjects) genotyped on the Affymetrix
      GeneChip 6.0 array. We applied two phenotypic approaches: (1) categorical case
      control comparisons (CC) based upon psychiatric diagnoses, and (2) quantitative
      phenotypic factor scores (FS) derived from a multivariate analysis combining
      information across the clinical phenotypes. Linear and logistic models were used
      to analyse the association with ADs using FS and CC traits, respectively. At the
      single locus level, no genome-wide significant association was found. A trans
      population gene-based meta-analysis across both ethnic subsamples using FS
      identified three genes (MFAP3L on 4q32.3, NDUFAB1 and PALB2 on 16p12) with genome
      wide significance (false discovery rate (FDR] <5%). At the pathway level, several
      terms such as transcription regulation, cytokine binding, and developmental
      process were significantly enriched in ADs (FDR <5%). Our approaches studying ADs
      as quantitative traits and utilizing the full GWAS data may be useful in
      identifying susceptibility genes and pathways for ADs. 

PMID- 25390647
TI  - Small drains, big problems: the impact of dry weather runoff on shoreline water
      quality at enclosed beaches.
AB  - Enclosed beaches along urban coastlines are frequent hot spots of fecal indicator
      bacteria (FIB) pollution. In this paper we present field measurements and
      modeling studies aimed at evaluating the impact of small storm drains on FIB
      pollution at enclosed beaches in Newport Bay, the second largest tidal embayment
      in Southern California. Our results suggest that small drains have a
      disproportionate impact on enclosed beach water quality for five reasons: (1) dry
      weather surface flows (primarily from overirrigation of lawns and ornamental
      plants) harbor FIB at concentrations exceeding recreational water quality
      criteria; (2) small drains can trap dry weather runoff during high tide, and then
      release it in a bolus during the falling tide when drainpipe outlets are exposed;
      (3) nearshore turbulence is low (turbulent diffusivities approximately 10(-3)
      m(2) s(-1)), limiting dilution of FIB and other runoff-associated pollutants once
      they enter the bay; (4) once in the bay, runoff can form buoyant plumes that
      further limit vertical mixing and dilution; and (5) local winds can force buoyant
      runoff plumes back against the shoreline, where water depth is minimal and human
      contact likely. Outdoor water conservation and urban retrofits that minimize the
      volume of dry and wet weather runoff entering the local storm drain system may be
      the best option for improving beach water quality in Newport Bay and other urban
      impacted enclosed beaches. 

PMID- 25390646
TI  - Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon
      development.
AB  - Hereditary spastic paraplegias (HSPs) are a genetically diverse group of
      inherited neurological disorders (SPG1-72) with the cardinal feature of prominent
      lower-extremity spasticity due to a length-dependent axonopathy of corticospinal
      motor neurons. The most frequent form of autosomal dominant HSP results from
      mutations of the SPG4 gene product spastin. This is an ATPase associated with
      diverse cellular activities (AAA) protein that binds to and severs microtubules.
      While spastin participates in crucial cellular processes such as cytokinesis,
      endosomal tubulation, and axon development, its role in HSP pathogenesis remains
      unclear. Spastin interacts in cells with the NA14 protein, a major target for
      auto-antibodies in Sjogren's syndrome (nuclear autoantigen 1; SSNA1). Our
      analysis of endogenous spastin and NA14 proteins in HeLa cells and rat cortical
      neurons in primary culture revealed a clear distribution of both proteins to
      centrosomes, with NA14 localizing specifically to centrioles. Stable NA14
      knockdown in cell lines dramatically affected cell division, in particular
      cytokinesis. Furthermore, overexpression of NA14 in neurons significantly
      increased axon outgrowth and branching, while also enhancing neuronal
      differentiation. We postulate that NA14 may act as an adaptor protein regulating
      spastin localization to centrosomes, temporally and spatially regulating the
      microtubule-severing activity of spastin that is particularly critical during the
      cell cycle and neuronal development. 

PMID- 25390648
TI  - A study on the digestive physiology of a marine polychaete (Eulalia viridis)
      through microanatomical changes of epithelia during the digestive cycle.
AB  - As for many invertebrates, the gut of marine polychaete species has key
      physiological functions. However, studies integrating microanatomical
      descriptions with physiological processes are scarce. The present investigates
      histological, histochemical and cytological changes in the alimentary canal
      during the digestive cycle of the marine annelid Eulalia viridis, a species that
      combines opportunist scavenging, predation and cannibalistic behavior. The gut is
      comprised of an eversible pharynx, esophagus, intestine and rectum. Three main
      phases of digestion were identified, namely, resting/secretory, absorptive and
      excretory. The intestinal epithelium is complex and exhibited the most
      significant changes regarding intracellular digestion, excretion and storage.
      Conversely, the pharynx and esophagus were chiefly important for enzyme
      secretion. The results also indicate the existence of two distinct types of
      secretory cells in the intestine, with likely distinct physiological roles. Some
      similarities have been found between the intestinal epithelia and the molluscan
      (especially cephalopod) digestive gland, as, for instance, the shedding of apical
      corpuscles by digestive cells at posterior stages of digestion. The findings
      indicate that the digestive process in this worm is complex and related to the
      many physiological roles that cells need to play in the presence of reduced organ
      differentiation. 

PMID- 25390649
TI  - Effects of radiofrequency catheter ablation of atrial fibrillation on soluble P
      selectin, von Willebrand factor and IL-6 in the peripheral and cardiac
      circulation.
AB  - BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is associated with
      inflammatory response, endothelial damage and with increased risk of thrombosis.
      However, whether these processes differ in peripheral and cardiac circulation is
      unknown. METHODS: Plasma markers (von Willebrand factor (vWf), soluble P-selectin
      (sPsel) and interleukin-6 (IL-6)) were measured by ELISA at three time points in
      80 patients (62+/-10 years, 63% males, 41% paroxysmal AF) undergoing CA. These
      were at baseline--from femoral vein (FV) and left atrium (LA) before ablation;
      directly after ablation--from the pulmonary vein (PV), LA and FV; and 24 hours
      after procedure--from a cubital vein (CV). RESULTS: The levels of vWF and IL6-
      but not sP-sel--increased significantly 24 h after procedure (p<0.001). Baseline
      vWF was significantly associated with persistent AF (Beta = .303, p = 0.006 and
      Beta = .300, p = 0.006 for peripheral and cardiac levels, respectively), while
      persistent AF (Beta = .250, p = 0.031) and LAA flow pattern (Beta = .386,
      p<0.001) remained associated with vWF in cardiac blood after ablation. Advanced
      age was significantly associated with IL6 levels at baseline and after ablation
      in peripheral and cardiac blood. There were no clinical, procedural or anti
      coagulation characteristics associated with sP-sel levels in cardiac blood, while
      peripheral sP-sel levels were associated with hypertension before (Beta = -.307,
      p = 0.007) and with persistent AF after ablation (Beta = -.262, p = 0.020).
      CONCLUSIONS: vWF levels are higher in persistent AF and are associated with LAA
      rheological pattern after AF ablation. Increase of peripheral vWF and IL6 levels
      after procedure supports current AF ablation management with careful control of
      post-procedural anticoagulation to avoid ablation-related thromboembolism.

PMID- 25390650
TI  - Biomarkers of manganese exposure in pregnant women and children living in an
      agricultural community in California.
AB  - Manganese (Mn) is an essential nutrient but at high exposure levels is a
      neurotoxicant. There is no well-validated biomarker to assess perinatal Mn
      exposure. A total of 75 mother-child pairs provided blood, urine, and/or
      deciduous tooth samples. We analyzed Mn in dentin and enamel of shed teeth;
      maternal, cord, and child blood; and maternal and child urine and examined the
      interrelationships of Mn levels in all matrices. We observed higher Mn levels in
      prenatal than postnatal dentin (geometric mean (GM) = 0.51 vs 0.16 Mn:Ca, p <
      0.001), maternal blood at delivery than 26 weeks gestation (GM = 20.7 vs. 14.6
      MUg/L, p = 0.001), and cord blood than child blood at 24 months of age (39.9 vs
      25.0 MUg/L, p = 0.005). There were no significant correlations between Mn in
      dentin and Mn concentrations in maternal blood or maternal or child urine. Levels
      of Mn in prenatal dentin, prenatal maternal blood, and 24 month urine were higher
      (p < 0.05) among mothers and children living with a farm worker. Prenatal Mn
      levels in dentin were correlated with Mn loadings and concentrations in prenatal
      house dust. Levels of Mn measured in tooth dentin constitute a promising
      biomarker of perinatal exposure. 

PMID- 25390651
TI  - Accelerated recovery of mitochondrial membrane potential by GSK-3beta
      inactivation affords cardiomyocytes protection from oxidant-induced necrosis.
AB  - Loss of mitochondrial membrane potential (DeltaPsim) is known to be closely
      linked to cell death by various insults. However, whether acceleration of the
      DeltaPsim recovery process prevents cell necrosis remains unclear. Here we
      examined the hypothesis that facilitated recovery of DeltaPsim contributes to
      cytoprotection afforded by activation of the mitochondrial ATP-sensitive K+
      (mKATP) channel or inactivation of glycogen synthase kinase-3beta (GSK-3beta).
      DeltaPsim of H9c2 cells was determined by tetramethylrhodamine ethyl ester (TMRE)
      before or after 1-h exposure to antimycin A (AA), an inducer of reactive oxygen
      species (ROS) production at complex III. Opening of the mitochondrial
      permeability transition pore (mPTP) was determined by mitochondrial loading of
      calcein. AA reduced DeltaPsim to 15 +/- 1% of the baseline and induced calcein
      leak from mitochondria. DeltaPsim was recovered to 51 +/- 3% of the baseline and
      calcein-loadable mitochondria was 6 +/- 1% of the control at 1 h after washout of
      AA. mKATP channel openers improved the DeltaPsim recovery and mitochondrial
      calcein to 73 +/- 2% and 30 +/- 7%, respectively, without change in DeltaPsim
      during AA treatment. Activation of the mKATP channel induced inhibitory
      phosphorylation of GSK-3beta and suppressed ROS production, LDH release and
      apoptosis after AA washout. Knockdown of GSK-3beta and pharmacological inhibition
      of GSK-3beta mimicked the effects of mKATP channel activation. ROS scavengers
      administered at the time of AA removal also improved recovery of DeltaPsim. These
      results indicate that inactivation of GSK-3beta directly or indirectly by mKATP
      channel activation facilitates recovery of DeltaPsim by suppressing ROS
      production and mPTP opening, leading to cytoprotection from oxidant stress
      induced cell death.

PMID- 25390652
TI  - Defects in the acquisition of tumor-killing capability of CD8+ cytotoxic T cells
      in streptozotocin-induced diabetic mice.
AB  - Emerging evidences have shown that diabetes mellitus not only raises risk but
      also heightens mortality rate of cancer. It is not clear, however, whether
      antitumor CD8+ cytotoxic T lymphocyte (CTL) response is down-modulated in
      diabetic hosts. We investigated the impact of hyperglycemia on CTLs' acquisition
      of tumor-killing capability by utilizing streptozotocin-induced diabetic (STZ
      diabetic) mice. Murine diabetes was induced by intraperitoneal injection of STZ
      (200 mg/kg) in C57BL/6 mice, 2C-T cell receptor (TCR) transgenic and P14-TCR
      transgenic mice. The study found that, despite harboring intact proliferative
      capacity measured with CFSE labeling and MTT assay, STZ-diabetic CD8+ CTLs
      displayed impaired effector functions. After stimulation, STZ-diabetic CD8+ CTLs
      produced less perforin and TNFalpha assessed by intracellular staining, as well
      as expressed less CD103 protein. Furthermore, adoptive transfer of STZ-diabetic
      P14 CD8+ effector cells showed an insufficient recruitment to the B16.gp33
      melanoma and inadequate production of perforin, granzyme B and TNFalpha
      determined by immunohistochemistry in the tumor milieu. As a result, STZ-diabetic
      CD8+ effector cells were neither able to eliminate tumor nor to improve survival
      of tumor-bearing mice. Taken together, our data suggest that CD8+ CTLs are
      crippled to infiltrate into tumors and thus fail to acquire tumor-killing
      capability in STZ-diabetic hosts. 

PMID- 25390653
TI  - Simplexide induces CD1d-dependent cytokine and chemokine production from human
      monocytes.
AB  - Monocytes are major effector cells of innate immunity and recognize several
      endogenous and exogenous molecules due to the expression of wide spectrum of
      receptors. Among them, the MHC class I-like molecule CD1d interacts with
      glycolipids and presents them to iNKT cells, mediating their activation.
      Simplexide belongs to a novel class of glycolipids isolated from marine sponges
      and is structurally distinct from other immunologically active glycolipids. In
      this study we have examined the effects of simplexide on cytokine and chemokine
      release from human monocytes. Simplexide induces a concentration- and time
      dependent release of IL-6, CXCL8, TNF-alpha and IL-10 and increases the
      expression of IL6, CXCL8 and IL10 mRNA. Cytokine and chemokine release induced by
      simplexide from monocytes is dependent on CD1d since: i) a CD1d antagonist, 1,2
      bis (diphenylphosphino) ethane [DPPE]-polyethylene glycolmonomethylether [PEG],
      specifically blocks simplexide-induced activation of monocytes; ii) CD1d
      knockdown inhibits monocyte activation by simplexide and iii) simplexide induces
      cytokine production from CD1d-transfected but not parental C1R cell line.
      Finally, we have shown that simplexide also induces iNKT cell expansion in vitro.
      Our results demonstrate that simplexide, apart from activating iNKT cells,
      induces the production of cytokines and chemokines from human monocytes by direct
      interaction with CD1d.

PMID- 25390654
TI  - Pyrethroids differentially alter voltage-gated sodium channels from the honeybee
      central olfactory neurons.
AB  - The sensitivity of neurons from the honey bee olfactory system to pyrethroid
      insecticides was studied using the patch-clamp technique on central 'antennal
      lobe neurons' (ALNs) in cell culture. In these neurons, the voltage-dependent
      sodium currents are characterized by negative potential for activation, fast
      kinetics of activation and inactivation, and the presence of cumulative
      inactivation during train of depolarizations. Perfusion of pyrethroids on these
      ALN neurons submitted to repetitive stimulations induced (1) an acceleration of
      cumulative inactivation, and (2) a marked slowing of the tail current recorded
      upon repolarization. Cypermethrin and permethrin accelerated cumulative
      inactivation of the sodium current peak in a similar manner and tetramethrin was
      even more effective. The slow-down of channel deactivation was markedly dependent
      on the type of pyrethroid. With cypermethrin, a progressive increase of the tail
      current amplitude along with successive stimulations reveals a traditionally
      described use-dependent recruitment of modified sodium channels. However, an
      unexpected decrease in this tail current was revealed with tetramethrin. If one
      considers the calculated percentage of modified channels as an index of
      pyrethroids effects, ALNs are significantly more susceptible to tetramethrin than
      to permethrin or cypermethrin for a single depolarization, but this difference
      attenuates with repetitive activity. Further comparison with peripheral neurons
      from antennae suggest that these modifications are neuron type specific. Modeling
      the sodium channel as a multi-state channel with fast and slow inactivation
      allows to underline the effects of pyrethroids on a set of rate constants
      connecting open and inactivated conformations, and give some insights to their
      specificity. Altogether, our results revealed a differential sensitivity of
      central olfactory neurons to pyrethroids that emphasize the ability for these
      compounds to impair detection and processing of information at several levels of
      the bees olfactory pathway. 

PMID- 25390656
TI  - Preischemic Administration of Sevoflurane Does not Exert Dose-dependent Effects
      on the Outcome of Severe Forebrain Ischemia in Rats.
AB  - We previously showed that preischemic administration of high-dose isoflurane
      worsened the outcome from severe forebrain ischemia in rats. Conversely, high
      doses of sevoflurane have been reported to improve the outcome from forebrain
      ischemia when the insult is moderate. To clarify the dose-dependent effects of
      sevoflurane on severe forebrain ischemia, we performed an outcome study using an
      identical protocol to that in our previous study with isoflurane. Fasting male
      Sprague-Dawley rats underwent surgical preparation for forebrain ischemia under
      halothane anesthesia. Anesthesia was changed to fentanyl/nitrous oxide to
      eliminate the halothane, after which 30 minutes of 0.5, 1.0, 1.5, 2.0, or 2.5
      minimum alveolar concentration sevoflurane was administered. Ten minutes of
      ischemia was induced by bilateral carotid occlusion plus systemic hypotension, in
      which cessation of electroencephalographic activity was confirmed. Sevoflurane
      was discontinued and anesthesia continued with fentanyl/nitrous oxide for an
      additional 100 minutes. Outcome evaluation at 5 days postischemia included
      seizure incidence, mortality rate, neuromotor score, and histologic injuries to
      the cerebral cortex and hippocampal CA1 and CA3. Different doses of sevoflurane
      did not statistically affect seizure incidence (10.0% to 18.2%), mortality rate
      (20.0% to 46.7%), cortical damage (mild to moderate degree), or hippocampal CA1
      damage (93.7% to 96.7% neuronal necrosis) or CA3 damage (36.3% to 41.7%). Dose
      dependent effects of sevoflurane were not observed for any of the outcome
      variables assessed in this rat model of severe forebrain ischemia. 

PMID- 25390657
TI  - Anesthetic Management of a Child With Severe Dystonia and G6PD Deficiency for
      Deep Brain Stimulation.

PMID- 25390655
TI  - Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective
      cohort study and literature-based meta-analysis.
AB  - BACKGROUND: Short telomeres have been linked to various age-related diseases. We
      aimed to assess the association of telomere length with incident type 2 diabetes
      mellitus (T2DM) in prospective cohort studies. METHODS: Leucocyte relative
      telomere length (RTL) was measured using quantitative polymerase chain reaction
      in 684 participants of the prospective population-based Bruneck Study (1995
      baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n =
      479). Hazard ratios for T2DM were calculated across quartiles of baseline RTL
      using Cox regression models adjusted for age, sex, body-mass index, smoking,
      socio-economic status, physical activity, alcohol consumption, high-density
      lipoprotein cholesterol, log high-sensitivity C-reactive protein, and waist-hip
      ratio. Separate analyses corrected hazard ratios for within-person variability
      using multivariate regression calibration of repeated measurements. To
      contextualise findings, we systematically sought PubMed, Web of Science and
      EMBASE for relevant articles and pooled results using random-effects meta
      analysis. RESULTS: Over 15 years of follow-up, 44 out of 606 participants free of
      diabetes at baseline developed incident T2DM. The adjusted hazard ratio for T2DM
      comparing the bottom vs. the top quartile of baseline RTL (i.e. shortest vs.
      longest) was 2.00 (95% confidence interval: 0.90 to 4.49; P = 0.091), and 2.31
      comparing the bottom quartile vs. the remainder (1.21 to 4.41; P = 0.011). The
      corresponding hazard ratios corrected for within-person RTL variability were 3.22
      (1.27 to 8.14; P = 0.014) and 2.86 (1.45 to 5.65; P = 0.003). In a random-effects
      meta-analysis of three prospective cohort studies involving 6,991 participants
      and 2,011 incident T2DM events, the pooled relative risk was 1.31 (1.07 to 1.60;
      P = 0.010; I2 = 69%). CONCLUSIONS/INTERPRETATION: Low RTL is independently
      associated with the risk of incident T2DM. To avoid regression dilution biases in
      observed associations of RTL with disease risk, future studies should implement
      methods correcting for within-person variability in RTL. The causal role of short
      telomeres in T2DM development remains to be determined.

PMID- 25390660
TI  - Using ranibizumab to successfully treat choroidal neovascularization in a patient
      with persistent placoid maculopathy.
AB  - PURPOSE: The purpose of this study was to report the successful treatment of
      persistent placoid maculopathy with intravitreal ranibizumab. METHODS: A 60-year
      old man with an 8-year history of blurry vision was diagnosed with bilateral
      persistent placoid maculopathy complicated by a choroidal neovascular membrane.
      The left eye received two laser photocoagulation treatments. The right eye was
      injected twice with intravitreal bevacizumab and then 3 times with intravitreal
      ranibizumab over the course of 1 year. RESULTS: Visual acuity in the left eye
      dropped from 20/30 to 20/100 despite gradual resolution of fluid. However, visual
      acuity in the right eye improved from 20/50 to 20/25 where it remained for 24
      months after the last injection. CONCLUSION: Ranibizumab seems to be efficacious
      in the treatment of choroidal neo-vascularization in persistent placoid
      maculopathy.

PMID- 25390661
TI  - Rebound neovascularization during bevacizumab therapy.
AB  - PURPOSE: To present two cases of rebound neovascularization after bevacizumab
      treatment. METHODS: Observational, retrospective case report. A 42-year-old male
      patient with proliferative diabetic retinopathy and a 68-year-old man with
      central retinal vein occlusion received treatment with panretinal
      photocoagulation and intravitreal bevacizumab. RESULTS: Both patients showed
      significant improvement with regression of neovascular vessels after treatment.
      Nevertheless, on cessation of treatment because of loss to follow-up, both
      presented with massive neovascularization. This was significantly more severe
      than the initial presentation. CONCLUSION: After initial suppression of vascular
      endothelial growth factor by bevacizumab, a rebound phenomenon of
      neovascularization can occur.

PMID- 25390659
TI  - Effects of phosphorylatable short peptide-conjugated chitosan-mediated IL-1Ra and
      igf-1 gene transfer on articular cartilage defects in rabbits.
AB  - Previously, we reported an improvement in the transfection efficiency of the
      plasmid DNA-chitosan (pDNA/CS) complex by the utilization of phosphorylatable
      short peptide-conjugated chitosan (pSP-CS). In this study, we investigated the
      effects of pSP-CS-mediated gene transfection of interleukin-1 receptor antagonist
      protein (IL-1Ra) combined with insulin-like growth factor-1 (IGF-1) in rabbit
      chondrocytes and in a rabbit model of cartilage defects. pBudCE4.1-IL-1Ra+igf-1,
      pBudCE4.1-IL-1Ra and pBudCE4.1-igf-1 were constructed and combined with pSP-CS to
      form pDNA/pSP-CS complexes. These complexes were transfected into rabbit primary
      chondrocytes or injected into the joint cavity. Seven weeks after treatment, all
      rabbits were sacrificed and analyzed. High levels of IL-1Ra and igf-1 expression
      were detected both in the cell culture supernatant and in the synovial fluid. In
      vitro, the transgenic complexes caused significant proliferation of chondrocytes,
      promotion of glycosaminoglycan (GAG) and collagen II synthesis, and inhibition of
      chondrocyte apoptosis and nitric oxide (NO) synthesis. In vivo, the exogenous
      genes resulted in increased collagen II synthesis and reduced NO and GAG
      concentrations in the synovial fluid; histological studies revealed that pDNA/pSP
      CS treatment resulted in varying degrees of hyaline-like cartilage repair and
      Mankin score decrease. The co-expression of both genes produced greater effects
      than each single gene alone both in vitro and in vivo. The results suggest that
      pSP-CS is a good candidate for use in gene therapy for the treatment of cartilage
      defects and that igf-1 and IL-1Ra co-expression produces promising biologic
      effects on cartilage defects. 

PMID- 25390662
TI  - Repeated noninfectious endophthalmitis after intravitreal administration of
      bevacizumab: a report of two cases.
AB  - PURPOSE: To report on two patients with sterile endophthalmitis recurring twice
      after intravitreal bevacizumab injection. METHODS: Two cases of sterile
      intraocular inflammation recurring after repeated intravitreal injections of
      bevacizumab are described, followed by a review of the literature. RESULTS: Two
      patients presented with painful eyes and decreased vision associated with
      endophthalmitis several days after intravitreal bevacizumab injection. In both
      patients, vitreous specimens were sterile. The intraocular inflammation recurred
      after additional intravitreal injection of bevacizumab that was performed during
      subsequent follow-up. CONCLUSION: This is the first report of sterile intraocular
      inflammation recurring after repeated intravitreal injections of bevacizumab.
      Awareness of the possible association between bevacizumab administration and
      sterile endophthalmitis may be warranted.

PMID- 25390663
TI  - Multifocal electroretinogram in desferrioxamine-related macular toxicity.
AB  - PURPOSE: The purpose of the study was to evaluate focal macular function by using
      multifocal electroretinography in a patient presenting with features of
      desferrioxamine maculopathy. METHODS: This is an observational case-control study
      of a 74-year-old man taking desferrioxamine mesylate 40 mg/kg/d 4 to 5 times a
      week as an iron-chelating agent for 5 years. Desferrioxamine-related ocular
      toxicity presenting as bilaterally symmetrical pigmentary maculopathy was
      diagnosed by clinical examination and relevant history. Retinopathy was further
      corroborated with full-field electroretinography and multifocal
      electroretinography using VERIS Science 5.1 with Burian-Allen bipolar contact
      lens electrodes. First-order kernels were calculated and analyzed from six zones
      at different retinal eccentricities around the fovea. RESULTS: Clinical and
      electrophysiological investigations showed a bilaterally symmetric picture of
      desferrioxamine maculopathy, with P1 and N1 on multifocal electroretinography
      showing significantly reduced amplitudes and prolonged implicit times in both the
      eyes as compared with age-matched controls. CONCLUSION: Maculotoxicity may be the
      presenting feature of desferrioxamine toxicity, and multifocal
      electroretinography allows simultaneous measurements of multiple focal macular
      responses in these cases.

PMID- 25390664
TI  - Optical coherence tomography findings in deferasirox-related maculopathy.
AB  - PURPOSE: To describe a 17-year-old boy with beta-thalassemia on oral deferasirox,
      a novel once-daily oral iron chelator, who presented with bilateral painless
      visual loss, central scotomas, and dyschromatopsia. METHODS: Case report.
      RESULTS: Fluorescein angiography and full-field electroretinography were normal;
      initial diagnosis of toxic optic neuropathy secondary to deferasirox was made.
      However, optical coherence tomography (OCT) revealed no abnormalities in the
      retinal nerve fiber layer but demonstrated thinning of the outer retina, with
      disruption of the inner/outer segment (IS/OS) junction in the perifoveal regions
      in both eyes. CONCLUSION: These findings on OCT suggested toxic maculopathy
      secondary to deferasirox. This case highlights the importance of OCT in the early
      detection of toxic retinal disorders, especially when other standard tests are
      nonrevealing. This is the first documented case of deferasirox-induced
      maculopathy and of deferasirox-related changes demonstrated on OCT.

PMID- 25390665
TI  - Retinoblastoma in oculocutaneous albinism.
AB  - PURPOSE: To report a case of retinoblastoma in a child with oculocutaneous
      albinism (OCA). METHODS: A 24-month-old girl with classic features of OCA
      developed leukocoria in the left eye. RESULTS: The patient was found to have an
      endophytic retinoblastoma and an exophytic retinoblastoma, with a total retinal
      detachment and neovascularization of the iris. Enucle-ation was performed, and
      histopathology confirmed massive retinoblastoma with optic nerve involvement to
      the posterior margin of the lamina cribrosa but no choroidal invasion.
      CONCLUSION: Although rare, retinoblastoma can occur in children with OCA.

PMID- 25390666
TI  - Anterior segment retinoblastoma detectable on magnetic resonance imaging.
AB  - PURPOSE: To report a case of retinoblastoma infiltrating the iris and ciliary
      body detected on magnetic resonance imaging. METHODS: A retrospective case report
      with clinical evaluation, diagnostic testing, enucleation, and pathologic
      description. RESULTS: A 2-year-old boy presented with hyphema and was noted to
      have a fluffy whitish iris mass. Retinoblastoma with anterior chamber extension
      was suggested on magnetic resonance imaging. T2-weighted images demonstrated a
      hypointense mass with a superficial layer of focal marked hypointensity,
      consistent with hemorrhage or calcification. Enucleation was performed, and
      histopathology confirmed retinoblastoma infiltrating the iris and ciliary body.
      No further treatment was administered, and the patient remains free of associated
      disease at age 5 years. CONCLUSION: Retinoblastoma can invade the iris and
      ciliary body stroma. The use of magnetic resonance imaging in evaluating cases of
      anterior segment masses can demonstrate findings suggestive of retinoblastoma.

PMID- 25390667
TI  - Paraneoplastic vitelliform retinopathy in metastatic cutaneous melanoma.
AB  - PURPOSE: To report the clinical picture and investigative findings of unusual
      paraneoplastic retinopathy lesions in a patient with metastatic skin melanoma.
      METHODS: A middle-aged man presented with mild blurring of vision in one eye. He
      had metastatic skin melanoma to the axillary lymph nodes, which was treated by
      interferon. Fundus photographs showed bilateral unusual multiple vitelliform
      lesions. Retinal and serologic investigations were performed. RESULTS: These
      vitelliform lesions involved the outer retinal layers and retinal pigment
      epithelium (RPE) as demonstrated by optical coherence tomography and have
      completely blocked choroidal fluorescence without late staining in angiography.
      There was only minimal reduction of Arden ratio in electro-oculography, although
      electroretinography was essentially normal. Antibipolar cells autoantibodies were
      not detected in this case. CONCLUSION: This melanoma-related paraneoplastic
      retinopathy may represent a separate entity from the classic findings in melanoma
      associated retinopathy (MAR) syndrome. Optical coherence tomography is helpful to
      differentiate it from simulating lesions. Recognition of this presentation can
      help to diagnose the presence of an occult metastaticmelanoma in some cases.

PMID- 25390668
TI  - Submacular hydatid cyst: a case report.
AB  - PURPOSE: To report a rare case of submacular hydatid cyst and its surgical
      management. METHODS: Systemic investigations did not show a hydatid cyst in any
      other body organ. Serology for Echinococcus granulosus was also negative. Pars
      plana lensectomy and vitrectomy were done. Removal of the cyst was done with the
      help of foreign body forceps after debulking with cystostomy and silicone oil
      tamponade was given. Histopathologic examination showed it to be a hydatid cyst.
      CONCLUSION: Surgery for a subretinal hydatid cyst cytostomy is a safe treatment
      modality.

PMID- 25390669
TI  - Disappearance of drusen after rhegmatogenous retinal detachment.
AB  - PURPOSE: To describe the disappearance of drusen after rhegmatogenous retinal
      detachment. METHODS: Descriptive case report. RESULTS: A 72-year-old man with
      confluent subfoveal drusen developed a rhegmatogenous retinal detachment and
      subsequently improved in vision with disappearance of the subfoveal drusen less
      than 1 month after repair. CONCLUSION: Rhegmatogenous retinal detachment can
      result in the disappearance of drusen.

PMID- 25390670
TI  - Late-onset retinal macular degeneration: an entity not to be overlooked.
AB  - PURPOSE: To describe a patient with extensive geographic atrophy and night
      blindness. METHODS: A 59-year-old Caucasian woman of German descent presenting
      with progressive visual difficulty in the dark for 5 years was examined. RESULTS:
      Her visual acuity was 20/400 in the right eye and 20/50 in the left eye. Fundus
      examination of both eyes showed multiple islands of geographic atrophy involving
      most of the posterior pole and temporal retina. There were yellow drusen-like
      flecks in the nasal retina. The fluorescein angiogram showed window defects and
      the corresponding atrophic areas showed decreased autofluorescence. A Goldmann
      visual field showed central scotoma and marked constriction on the right and
      moderate constriction on the left. An electroretinogram showed markedly decreased
      rod and cone function in both eyes. CONCLUSION: Late-onset retinal macular
      degeneration is a rare degenerative condition that should not be mistaken for age
      related macular degeneration.

PMID- 25390671
TI  - Choroidal ischemia secondary to a diving injury.
AB  - PURPOSE: To report a case of choroidal ischemia in a professional diver after a
      decompression sickness accident. METHODS: A 31-year-old man presented a
      decompression sickness accident without any systemic manifestation. The symptoms
      were exclusively ophthalmic with sudden decrease of vision and presence of
      scotoma predominantly on the left eye immediately after a dive. The patient had a
      complete clinical ophthalmologic examination as well as fluorescein angiography,
      optical coherence tomography, central visual field, visual-evoked potentials, and
      electroretinogram examinations that were repeated during the follow-up over a
      period of 18 months. RESULTS: The examinations performed 1 week after the
      decompression sickness accident and the hyperbaric oxygen therapy showed
      diminution of foveal reflectivity associated with retinal pigment epithelium
      modifications, deficit of choroidal perfusion in the macular region, and
      important central scotoma in both eyes. During the follow-up, the central scotoma
      disappeared after 6 months. The retinal pigment epithelium presented pigmentary
      migrations without subretinal fluid accumulation. CONCLUSION: This case report
      describes choroidal ischemia resulting from decompression-induced intravascular
      gaseous microemboli caused by a decompression sickness diving accident.

PMID- 25390672
TI  - Hypertensive retinopathy grade iv in an 11-year-old girl with renal arterial
      hypertension due to recurrent reflux pyelonephritis.
AB  - PURPOSE: The prevalence of retinal vascular abnormalities in children is shown to
      be similar to that in adults. Swelling of the optic disk in children may have
      different etiologies. The differential diagnosis necessitates an
      interdisciplinary workup. METHODS: This study presents a case of bilateral edema
      of the optic disk with unilateral diminution of visual acuity in an 11-year-old
      girl due to malignant hypertension caused by reflux nephropathy in consequence of
      vesicoureteric reflux and recurrent urinary tract infections. CONCLUSION: Early
      diagnosis of malignant hypertension in children and adequate therapy are
      essential for avoiding permanent visual dysfunction.

PMID- 25390673
TI  - Spontaneous closure of a posttraumatic scleral fistula in an atypical choroidal
      coloboma.
AB  - BACKGROUND: Scleral fistulas have been reported to occur in choroidal colobomas,
      and their repair has been described in the literature. Spontaneous closure of a
      posttraumatic fistula has not been reported. PURPOSE: To describe the occurrence
      of posttraumatic scleral fistula formation and its spontaneous closure in an eye
      with an atypical choroidal coloboma. METHODS: Interventional case report.
      RESULTS: Spontaneous closure of the posttraumatic scleral fistula was noted at 1
      month follow-up. This was documented clinically and confirmed by B-scan
      ultrasound. CONCLUSION: Scleral fistula formation can occur at the base of a
      choroidal coloboma after blunt injury, and this can close spontaneously over a
      period of time.

PMID- 25390674
TI  - Symptomatic dynamic vitreomacular traction during accommodation and head-down
      posture preceding definitive vitreomacular traction syndrome.
AB  - PURPOSE: To report a case of progressive vitreomacular traction, definitive
      optical coherence tomography evidence of established vitreomacular traction, and
      subsequent spontaneous resolution with posterior vitreous detachment occurrence.
      METHODS: Case report and literature review. This study involved a patient
      presenting to the Retina Clinic at Stoke Mandeville Hospital. RESULTS:
      Symptomatic improvement after posterior vitreous detachment. CONCLUSION: Dynamic
      vitreomacular traction should be suspected in cases of fluctuating central visual
      disturbance, particularly when associated with accommodation and downward head
      posture. The authors discuss the possible influence of accommodation and head
      position.

PMID- 25390675
TI  - Intraoperative mechanical failure of a 25-gauge vitreous cutter.
AB  - PURPOSE: To describe the mechanical failure of a 25-gauge vitreous cutter
      intraoperatively and the management of this complication. METHODS: An
      observational case report of a 39-year-old Type 1 diabetic woman with
      proliferative retinopathy who underwent pars plana vitrectomy with 25-gauge
      instrumentation. RESULTS: Breakage of the 25-gauge vitreous cutter occurred
      during delamination of a dense fibrovascular plaque. The cutter was successfully
      removed via the trocar as a single unit. The patient recovered with no sequelae.
      CONCLUSIONS: Breakage of 25-gauge instrumentation intraoperatively is a very rare
      event. This case constitutes only the second reported complication as such.
      However, it is easily managed and can result in few, if any, adverse sequelae.

PMID- 25390676
TI  - Progressive indocyanine green toxicity.
AB  - PURPOSE: To report a case of progressive indocyanine green (ICG) toxicity that
      occurred after pars plana vitrectomy for an epiretinal membrane. METHODS: The
      patient underwent pars plana vitrectomy for an epiretinal membrane. After fluid-
      air exchange, ICG was spread only on the macular area, and air-fluid exchange was
      performed immediately. The epiretinal membrane was removed with serrated forceps.
      RESULTS: Although the preoperative visual acuity was 0.6, it was 0.2 in the first
      postoperative month, and fundus fluorescein angiography revealed retinal pigment
      epithelium atrophy in the macula that matched the area of ICG application. Visual
      acuity in the fourth postoperative month was 0.1, and there was optic atrophy.
      During the sixth postoperative month, visual acuity was hand movements, and there
      were multiple retinal holes in the macula and sclerosis of the arteries.
      CONCLUSION: This study demonstrates that intravitreal use of ICG might have toxic
      effects on the retina. Unnecessary use of ICG should be avoided, and care must be
      taken when using intravitreal ICG.

PMID- 25390677
TI  - Spontaneous closure of macular hole in a patient with x-linked juvenile
      retinoschisis.
AB  - PURPOSE: To observe macular hole in a patient with juvenile retinoschisis.
      METHODS AND PATIENT: A 4-year-old boy with X-linked juvenile retinoschisis was
      examined and followed-up for 2 years. Optical coherence tomography was used to
      study his maculae. RESULTS AND DISCUSSION: A full-thickness macular hole was
      detected by clinical examination and optical coherence tomography. Spontaneous
      closure of the macular hole was noticed and confirmed by optical coherence
      tomography 2 years later with visual improvement. Macular hole in patients with
      juvenile retinoschisis should be observed for at least a short period of time
      before a surgical repair is considered.

PMID- 25390678
TI  - Central retinal artery occlusion after phacoemulsification.
AB  - PURPOSE: To report 2 cases of central retinal artery occlusion (CRAO) that
      occurred within 24 hours of routine phacoemulsification cataract surgery using
      peribulbar anesthesia. METHODS: Case 1: An otherwise well 76-year-old woman with
      right pseudoexfoliation syndrome and bilateral open angle glaucoma presented with
      right visual acuity of counting fingers on the first postoperative day after
      cataract surgery. The CRAO was noted on fundoscopy. Emergency measures to reduce
      intraocular pressure (IOP) and hyperbaric oxygen treatment were performed. Case
      2: A 59-year-old man with a history of non-Hodgkin's lymphoma, hypertension,
      hyperlipidemia, and ischemic stroke was similarly diagnosed with CRAO on the
      first postoperative day, with left visual acuity of counting fingers. RESULTS:
      The final visual acuity remained at counting fingers in both cases. CONCLUSION:
      Central retinal artery occlusion after routine cataract surgery is unusual. We
      review the literature on CRAO after routine intraocular procedures and propose
      three hypotheses regarding the potential mechanisms involved. A vasoconstrictive
      effect of the anesthetic agent on the central retinal artery, a rise in lOPs
      after anesthesia administration resulting in closure of the central retinal
      artery, and a mechanical effect of the volume of anesthetic on the central
      retinal artery are considered as plausible mechanisms, with a mechanical effect
      being the favored hypothesis.

PMID- 25390679
TI  - The inner limiting membrane does not regrow after indocyanine green-guided
      peeling: photo-report of two cases.
AB  - PURPOSE: The purpose of this study is to report two photo-cases of inner limiting
      membrane (ILM) defect staining during repeated vitrectomy. METHODS: This study is
      an interventional case report. Two cases are reported in which the ILM defect was
      indocyanine green (ICG) stained and photographed during repeated vitrectomy for a
      persistent macular hole. RESULTS: The ICG dye demonstrated a large circular area
      of nonstaining centered on the macular hole, corresponding to the area denuded of
      the ILM in the first operation. These areas were documented by video photography.
      CONCLUSION: The ILM most probably does not regrow after peeling in a way that it
      could be stained by ICG. A successful ILM peeling does not guarantee closure of
      macular hole, but repeated ILM peeling may have additional beneficial effect.

PMID- 25390680
TI  - Correspondence.

PMID- 25390681
TI  - Letters to the editor.

PMID- 25390682
TI  - Reply.

PMID- 25390684
TI  - Japanese encephalitis virus upregulates the expression of SOCS3 in mouse brain
      and Raw264.7 Cells.
AB  - Japanese encephalitis virus (JEV) is one of the pathogens that can invade the
      central nervous system, causing acute infection and inflammation of brain. SOCS3
      protein plays a vital role in immune processes and inflammation of the central
      nervous system. In this study, Raw264.7 cells and suckling mice were infected
      with JEV, and SOCS3 expression was analyzed by the gene expression profile,
      semiquantitative RT-PCR, qRT-PCR, immunohistochemistry (IHC) and Western blot.
      Results indicated that 520 genes were found to be differentially expressed (fold
      change >= 2.0, p < 0.05) in total. The differentially regulated genes were
      involved in biological processes, such as stimulus response, biological
      regulation and immune system processes. JEV early infection could induce SOCS3
      expression, upregulating both the mRNA and protein levels in Raw264.7 cells in a
      time-dependent manner. The SOCS3 expression was much lower in Raw264.7 cells
      infected with inactivated JEV than wild-type JEV. In vivo, SOCS3 protein was also
      found to upregulate the expression of mRNA and protein in JEV-infected mouse
      brain. Taken together, our data showed that JEV early infection could induce the
      upregulation of SOCS3 expression, both in vitro and in vivo, providing the basic
      theoretical foundation for future research on the invasion mechanism of JEV.

PMID- 25390683
TI  - A unique evolution of the s2 gene of equine infectious anemia virus in hosts
      correlated with particular infection statuses.
AB  - Equine infectious anemia virus (EIAV) is a member of the Lentivirus genus in the
      Retroviridae family that exhibits a genomic structure similar to that of HIV-1.
      The S2 accessory proteins play important roles in viral replication in vivo and
      in viral pathogenicity; however, studies on S2 evolution in vivo are limited.
      This study analyzed the evolutionary characteristics of the S2 gene of a
      pathogenic EIAV strain, EIAVLN40, in four experimentally infected horses. The
      results demonstrated that 14.7% (10 of 68 residues) of the stable amino acid
      mutations occurred longitudinally in S2 during a 150-day infection period.
      Further analysis revealed that six of the ten mutated residues were positively
      selected during the infection. Alignment and phylogenetic analyses showed that
      the S2 gene sequences of viruses isolated from the infected horses at the early
      stage of EIAVLN40 infection were highly homologous and similar to the vaccine
      specific sequence. The S2 gene variants isolated from the febrile episodes and
      late phase of infection became homologous to the S2 gene sequence of the
      inoculating EIAVLN40 strain. Our results indicate that the S2 gene evolves in
      diversity and divergence in vivo in different stages of EIAV infection and that
      this evolution correlates with the pathogenicity of the virus.

PMID- 25390685
TI  - Systematic analysis of new drug indications by drug-gene-disease coherent
      subnetworks.
AB  - Drug targets and disease genes may work as driver factors at the transcriptional
      level, which propagate signals through gene regulatory network and cause the
      downstream genes' differential expression. How to analyze transcriptional
      response data to identify meaningful gene modules shared by both drugs and
      diseases is still a critical issue for drug-disease associations and molecular
      mechanism. In this article, we propose the drug-gene-disease coherent subnetwork
      concept to group the biological function related drugs, diseases, and genes. It
      was defined as the subnetwork with drug, gene, and disease as nodes and their
      interactions coherently crossing three data layers as edges. Integrating
      differential expression profiles of 418 drugs and 84 diseases, we develop a
      computational framework and identify 13 coherent subnetworks such as inflammatory
      bowel disease and melanoma relevant subnetwork. The results demonstrate that our
      coherent subnetwork approach is able to identify novel drug indications and
      highlight their molecular basis. 

PMID- 25390686
TI  - Linking the population pharmacokinetics of tenofovir and its metabolites with its
      cellular uptake and metabolism.
AB  - Empirical pharmacokinetic models are used to explain the pharmacokinetics of the
      antiviral drug tenofovir (TFV) and its metabolite TFV diphosphate (TFV-DP) in
      peripheral blood mononuclear cells. These empirical models lack the ability to
      explain differences between the disposition of TFV-DP in HIV-infected patients
      vs. healthy individuals. Such differences may lie in the mechanisms of TFV
      transport and phosphorylation. Therefore, we developed an exploratory model based
      on mechanistic mass transport principles and enzyme kinetics to examine the
      uptake and phosphorylation kinetics of TFV. TFV-DP median Cmax from the model was
      38.5 fmol/10(6) cells, which is bracketed by two reported healthy volunteer
      studies (38 and 51 fmol/10(6) cells). The model presented provides a foundation
      for exploration of TFV uptake and phosphorylation kinetics for various routes of
      TFV administration and can be updated as more is known on actual mechanisms of
      cellular transport of TFV. 

PMID- 25390687
TI  - Acute fulminant hepatitis E virus genotype 3e infection: description of the first
      case in Europe.

PMID- 25390688
TI  - Cytomegalovirus-associated transverse myelitis: a review of nine well-documented
      cases.
AB  - Abstract Cytomegalovirus-associated transverse myelitis is a rare disease. We
      found 12 cases in the medical literature, 8 of which met our criteria for being
      well documented. Our aim was to review this clinical entity using information
      from our own clinical experience as well as published cases. 

PMID- 25390689
TI  - Acute fulminant vs. acute-on-chronic liver failure in hepatitis E: diagnostic
      implications.

PMID- 25390690
TI  - The Cys-Tyr cross-link of cysteine dioxygenase changes the optimal pH of the
      reaction without a structural change.
AB  - Cysteine dioxygenase (CDO) is a non-heme monoiron enzyme with an unusual
      posttranslational modification in the proximity of the ferrous iron active site.
      This modification, a cysteine to tyrosine thioether bond, cross-links two beta
      strands of the beta-barrel. We have investigated its role in catalysis through a
      combined crystallographic and kinetic approach. The C93G variant lacks the cross
      link and shows little change in structure from that of the wild type, suggesting
      that the cross-link does not stabilize an otherwise unfavorable conformation. A
      pH-dependent kinetic study shows that both cross-linked and un-cross-linked CDO
      are active but the optimal pH decreases with the presence of the cross-link. This
      result reflects the effect of the thioether bond on the pKa of Y157 and this
      residue's role in catalysis. At higher pH values, kcat is also higher for the
      cross-linked form, extending the pH range of activity. We therefore propose that
      the cross-link also increases activity by controlling deleterious interactions
      involving the thiol/ate of C93. 

PMID- 25390691
TI  - Analysis of second-line chemotherapies for ductal pancreatic adenocarcinoma in a
      German single-center cohort.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the third most common tumor of the
      gastrointestinal tract. At the time of diagnosis, the majority of PDACs shows
      already metastasis and does not qualify for curative surgery. Therefore,
      palliative chemotherapy has a very high priority, but recommendations after
      failure of first-line chemotherapies are quite limited. The aim of our analysis
      was to evaluate the efficacy of different second-line treatments after
      pretreatment with gemcitabine (57.5%), gemcitabine + erlotinib (25%), and
      platinum-based chemotherapy (17.5%). We included all patients with advanced PDAC
      treated with second-line chemotherapy in our department between 2005 and 2012. A
      total of 22 patients were treated with XELOX, 8 patients with FOLFOX, 6 patients
      with gemcitabine (+/- erlotinib) and 4 patients with FOLFIRI. On average, the
      patients received 4.2 cycles (standard deviation [SD] SD: 3.5) over a period of
      2.5 months (SD: 2.6). The median overall survival (OS) for all patients was 5.4
      months, progression-free survival was 3.5 months, and a tumor control was
      achieved in 21% of all cases. Toxicity profile was acceptable between the second
      line chemotherapies and there was no significant difference in the other
      investigated end points. Interestingly, there was also no effect of the first
      line treatment and their duration for the OS of the second-line therapy.
      According to our findings, second-line chemotherapies in advanced PDAC are
      beneficial and should be offered to patients, but we did not detect any
      superiority of a specific drug combination. More prospective, randomized and
      larger studies are necessary to evaluate new strategies for second-line
      chemotherapies.

PMID- 25390692
TI  - Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1
      receptors mediate Abeta 42 oligomer binding and synaptotoxicity.
AB  - Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild
      Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that
      underlie memory formation. Synaptic binding of Abeta oligomers to several
      putative receptor proteins is reported to inhibit long-term potentiation, affect
      membrane trafficking and induce reversible spine loss in neurons, leading to
      impaired cognitive performance and ultimately to anterograde amnesia in the early
      stages of Alzheimer's disease (AD). We have identified a receptor not previously
      associated with AD that mediates the binding of Abeta oligomers to neurons, and
      describe novel therapeutic antagonists of this receptor capable of blocking Abeta
      toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of
      sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in
      vitro using siRNA results in a highly correlated reduction in binding of
      exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma
      2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is
      dysregulated in Alzheimer's disease patients' brain compared to age-matched,
      normal individuals. Specific, high affinity small molecule receptor antagonists
      and antibodies raised against specific regions on this receptor can displace
      synthetic Abeta oligomer binding to synaptic puncta in vitro and displace
      endogenous human AD patient oligomers from brain tissue sections in a dose
      dependent manner. These receptor antagonists prevent and reverse the effects of
      Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive
      deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors
      mediate saturable oligomer binding to synaptic puncta on neurons and that brain
      penetrant, small molecules can displace endogenous and synthetic oligomers and
      improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key
      mediator of the pathological effects of Abeta oligomers in AD and is a tractable
      target for small molecule disease-modifying therapeutics. 

PMID- 25390693
TI  - alphaTubulin 67C and Ncd are essential for establishing a cortical microtubular
      network and formation of the Bicoid mRNA gradient in Drosophila.
AB  - The Bicoid (Bcd) protein gradient in Drosophila serves as a paradigm for gradient
      formation in textbooks. To explain the generation of the gradient, the ARTS
      model, which is based on the observation of a bcd mRNA gradient, proposes that
      the bcd mRNA, localized at the anterior pole at fertilization, migrates along
      microtubules (MTs) at the cortex to the posterior to form a bcd mRNA gradient
      which is translated to form a protein gradient. To fulfil the criteria of the
      ARTS model, an early cortical MT network is thus a prerequisite. We report
      hitherto undiscovered MT activities in the early embryo important for bcd mRNA
      transport: (i) an early and omnidirectional MT network exclusively at the
      anterior cortex of early nuclear cycle embryos showing activity during metaphase
      and anaphase only, (ii) long MTs up to 50 um extending into the yolk at
      blastoderm stage to enable basal-apical transport. The cortical MT network is not
      anchored to the actin cytoskeleton. The posterior transport of the mRNA via the
      cortical MT network critically depends on maternally-expressed alphaTubulin67C
      and the minus-end motor Ncd. In either mutant, cortical transport of the bcd mRNA
      does not take place and the mRNA migrates along another yet undisclosed interior
      MT network, instead. Our data strongly corroborate the ARTS model and explain the
      occurrence of the bcd mRNA gradient. 

PMID- 25390694
TI  - Single nucleotide polymorphisms in the 3'UTR of VPAC-1 cooperate in modulating
      gene expression and impact differently on the interaction with miR525-5p.
AB  - Complex immune and neurodegenerative disorders are the result of multiple
      interactions between common genetic variations having, individually, a weak
      effect on the disease susceptibility or resistance. Interestingly, some genes
      have been found to be associated with more than one disease although not
      necessarily the same SNPs are involved. In this context, single nucleotide
      polymorphisms in the 3'UTR region of type 1 receptor (VPAC-1) for vasoactive
      intestinal peptide (VIP) have been reported to be associated with some immune
      mediated as well as with neurodegenerative diseases such as Alzheimer's Disease
      (AD). Here, we demonstrate that variations at the 3'UTR of the VPAC-1 gene act
      synergistically to affect the expression of the luciferase as well as of the GFP
      reporter genes expressed in HEK293T cells. Moreover, the miRNA 525-5p, previously
      shown by us to target the 3'UTR of VPAC-1, is more efficient in decreasing GFP
      expression when co-expressed with constructs carrying the allele C at rs896
      (p<10(-3)) suggesting that this miRNA regulates VPAC-1 expression at different
      levels depending on rs896 polymorphism and thus adding complexity to the network
      of disease susceptibility.

PMID- 25390696
TI  - Spontaneous resolution of a rhegmatogenous retinal detachment after normal labor
      and childbirth.
AB  - PURPOSE: The purpose of this study was to describe a patient with an untreated
      rhegmatogenous retinal detachment, first diagnosed during pregnancy, that
      underwent spontaneous resolution after normal labor and childbirth. METHODS:
      Descriptive case report. RESULTS AND DISCUSSION: It has been extensively
      documented that normal labor and childbirth are safe in the context of
      rhegmatogenous retinal detachment. Although exudative retinal detachment is a
      well-known complication of preeclampsia, spontaneous reattachment of a
      rhegmatogenous retinal detachment is a rare phenomenon. In this case, labor
      induced physiologic changes may have contributed to the resolution of the
      detachment.

PMID- 25390697
TI  - Bilateral macular retinoschisis in a patient with x-linked alport syndrome.
AB  - PURPOSE: To report a case of bilateral macular retinoschisis in a patient with X
      linked Alport syndrome. METHODS: Observational case report. A 57-year-old woman
      with X-linked Alport syndrome who presented with bilateral macular retinoschisis,
      which was demonstrated by high-resolution optical coherence tomography. RESULTS:
      The patient's visual acuity was only mildly decreased, and she was observed for a
      period of 30 months. CONCLUSION: This is the first and only report of bilateral
      macular retinoschisis in a patient with Alport syndrome. We suggest that the
      basement membrane of Bruch's membrane and the retinal pigment epithelium may be
      impaired and permit passage of fluid into the retina resulting in retinoschisis.

PMID- 25390695
TI  - Association of interleukin 8 and myocardial recovery in patients with ST
      elevation myocardial infarction complicated by acute heart failure.
AB  - BACKGROUND: No data from controlled trials exists regarding the inflammatory
      response in patients with de novo heart failure (HF) complicating ST-elevation
      myocardial infarction (STEMI) and a possible role in the recovery of contractile
      function. We therefore explored the time course and possible associations between
      levels of inflammatory markers and recovery of impaired left ventricular function
      as well as levosimendan treatment in STEMI patients in a substudy of the
      LEvosimendan in Acute heart Failure following myocardial infarction (LEAF) trial.
      METHODS: A total of 61 patients developing HF within 48 hours after a primary PCI
      treated STEMI were randomised double-blind to a 25 hours infusion of levosimendan
      or placebo. Levels of IL-6, CRP, sIL-6R, sgp130, MCP-1, IL-8, MMP-9, sICAM-1,
      sVCAM-1 and TNF-alpha were measured at inclusion (median 22 h, interquartile
      range (IQR) 14, 29 after PCI), on day 1, day 2, day 5 and 6 weeks. Improvement in
      left ventricular function was evaluated as change in wall motion score index
      (WMSI) by echocardiography. RESULTS: Only circulating levels of IL-8 at inclusion
      were associated with change in WMSI from baseline to 6 weeks, r = / 0.41 (p =
      0.002). No association, however, was found between IL-8 and WMSI at inclusion or
      peak troponin T. Furthermore, there was a significant difference in change in
      WMSI from inclusion to 6 weeks between patients with IL-8 levels below, compared
      to above median value, / 0.44 (IQR / 0.57, / 0.19) vs. / 0.07 (IQR / 0.27, 0.07),
      respectively (p < 0.0001). Levosimendan did not affect the levels of inflammary
      markers compared to control. CONCLUSION: High levels of IL-8 in STEMI patients
      complicated with HF were associated with less improvement in left ventricular
      function during the first 6 weeks after PCI, suggesting a possible role of IL-8
      in the reperfusion-related injury of post-ischemic myocardium. Further studies
      are needed to confirm this hypothesis. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00324766.

PMID- 25390698
TI  - Sarcoid uveitis simulating birdshot chorioretinopathy in a child.
AB  - PURPOSE: To report a child with sarcoid choroidopathy that has a similar
      appearance to birdshot chorioretinopathy. METHODS: Observational case report.
      Review of the clinical examination, laboratory findings, and histopathologic
      records of a child with sarcoidosis. RESULTS: A 9-year-old girl was examined in a
      routine consultation demand in our pediatric clinic. Slit-lamp examination
      revealed granulomatous anterior uveitis, and funduscopic examination of both eyes
      revealed numerous, oval, irregular, creamy chorioretinal lesions. These were
      widespread throughout the fundus, except the macula, and had the characteristic
      funduscopic appearance of birdshot chorioretinopathy. The patient underwent
      axillary lymph node biopsy that showed noncaseating granulomas consistent with
      sarcoidosis. CONCLUSION: Sarcoidosis should be considered in a child with
      chorioretinal lesions resembling birdshot chorioretinopathy.

PMID- 25390699
TI  - Sympathetic ophthalmia after penetrating keratoplasty: a case report evaluated by
      spectral-domain optical coherence tomography.
AB  - BACKGROUND: Sympathetic ophthalmia is a rare, bilateral, diffuse granulomatous
      uveitis that usually occurs after open globe injury or intraocular surgery. To
      our knowledge, findings of this condition using spectral-domain optical coherence
      tomography have not been previously described. METHODS: Case report. RESULTS: A
      case of sympathetic uveitis after a tectonic corneal-scleral keratoplasty because
      of a fungal keratitis is reported. Spectral-domain optical coherence tomographic
      images revealed a multilobular serous retinal detachment in the sympathizing eye.
      The subretinal space was divided by thin septa into compartments filled with
      subretinal fluid and some high reflective compounds. CONCLUSION: Spectral-domain
      optical coherence tomographic imaging noninvasively demonstrated a multilobular
      serous retinal detachment in the sympathizing eye, sharing the same features
      previously reported in patients with Vogt-Koyanagi-Harada syndrome.

PMID- 25390700
TI  - Vitreous hemorrhage as the initial manifestation of idiopathic thrombocytopenic
      purpura.
AB  - PURPOSE: To report vitreous hemorrhage as the initial manifestation in idiopathic
      thrombocytopenic purpura, an uncommon presentation. METHODS: Case report.
      RESULTS: A 69-year-old white woman presented with diffuse vitreous hemorrhage as
      the initial manifestation of idiopathic thrombocytopenic purpura, 12 years after
      plaque radiotherapy for choroidal melanoma. CONCLUSION: Unexplained and recurrent
      vitreous hemorrhage should be evaluated for idiopathic thrombocytopenic purpura.

PMID- 25390701
TI  - Acute idiopathic maculopathy with coxsackievirus infection.
AB  - PURPOSE: To report a case of visual loss immediately after hand, foot, and mouth
      disease and demonstrate the high-resolution optical coherence tomography
      findings. METHODS: A retrospective case report of a 19-year-old nursery worker
      with resolving hand, foot, and mouth disease and acute unilateral visual loss.
      RESULTS: The clinical features were characteristic of unilateral acute idiopathic
      maculopathy. High-resolution optical coherence tomography demonstrated highly
      reflective subretinal material at the macula of one eye with disruption of the
      photoreceptor inner segment/outer segment junction. Vision remained poor for 4
      weeks when there was rapid recovery coinciding with reconstitution of the inner
      segment/outer segment junction on optical coherence tomography. CONCLUSION:
      Unilateral acute idiopathic maculopathy may be caused by Coxsackievirus
      infection. Optical coherence tomography and clinical findings suggest an acute
      viral retinal pigment epitheliitis to be the main pathologic feature.

PMID- 25390702
TI  - Bilateral subcutaneous emphysema from pressurized infusion during pars plana
      vitrectomy: a case report.
AB  - OBJECTIVES: To report a case of extensive subcutaneous emphysema introduced
      during vitrectomy while using an advanced feedback-controlled pressurized
      infusion system. METHODS: Clinical case report of a 56-year-old woman undergoing
      pars plana vitrectomy for rhegmatogenous retinal detachment of the left eye. The
      clinical and radiologic findings of the patient's eyes were documented. The
      mechanisms of feedback-controlled pressurized infusion devices were reviewed to
      explain the adverse events. A search of PubMed was conducted to look for any
      similar cases and/or discussion. RESULTS: In this surgical case, vitrectomy was
      completed with air-fluid exchange and a formed anterior chamber was observed with
      an estimated pressure of high teens to low 20s by the surgeon. After the
      undraping, the patient was noted to have severe facial crepitus extending to the
      clavicles. Immediate chest X-ray was done, followed by computed tomography,
      confirming orbital and subcutaneous emphysema, as well as the presence of
      perfluoro-N-octane in the left orbit. CONCLUSION: Integrated pressurized infusion
      devices using feedback sensors allow for a sophisticated method of maintaining
      intraocular pressure and globe formation. However, inadvertent or occult globe
      rupture may lead to disruption of feedback control and subsequent high rates of
      infusion. As the infused substances exit the site of rupture, they can lead to
      extensive extraocular gas or fluid accumulation, and we report a case of severe
      bilateral subcutaneous emphysema as a result.

PMID- 25390703
TI  - Cavernous hemangioma of the optic disk.
AB  - PURPOSE: To report a case of an unusually large cavernous hemangioma of the optic
      disk. METHOD: Case report with funduscopic, fluorescein angiography, and magnetic
      resonance imaging correlations. A 20-year-old woman with no ocular or systemic
      history was diagnosed with cavernous hemangioma of the optic disk in a routine
      eye examination. RESULTS: Fundus examination revealed an extremely large
      cavernous hemangioma of the optic disk, almost 4.5 disk diameter. Fluorescein
      angiography showed delayed filling of the lesion with intravascular plasma
      erythrocyte separation and no leakage. No systemic involvement was found.
      CONCLUSION: This case represents an atypical presentation of cavernous hemangioma
      of the optic disk, among the largest reported in the literature. After a 5-year
      follow up period, no change has been documented.

PMID- 25390704
TI  - Unusual maculopathy secondary to hypergammaglobulinemia in a patient with
      systemic lupus erythematosus.
AB  - PURPOSE: To report the unusual findings of fluorescein angiography and optical
      coherence tomography in a case of systemic lupus erythematosus with
      hypergammaglobulinemia. DESIGN: Interventional case report. RESULTS: A 59-year
      old woman had systemic lupus erythematosus but had stopped taking medication for
      6 months. Blurred vision was noted, and the fundoscopic findings revealed serous
      macular detachment. Results of optical coherence tomography demonstrated
      intraretinal and subretinal fluid, but fluorescein angiography showed no leakage.
      Her best-corrected visual acuity improved after posterior sub-Tenon triamcinolone
      injection. CONCLUSION: Patients with atypical macular detachment may be afflicted
      with a serum immunogammopathy such as multiple myeloma, Waldenstrom's
      macroglobulinemia, and benign polyclonal gammopathy. Systemic lupus erythematosus
      should also be ruled out.

PMID- 25390705
TI  - Posterior scleritis in a 9-year-old boy: a case report.
AB  - PURPOSE: To report a case of posterior scleritis in a 9-year-old boy. METHOD: A
      case report. RESULTS: Uniocular presentation in a 9-year-old boy. CONCLUSION:
      Posterior scleritis is seen commonly in middle-aged women, associated with mild
      ocular congestion, globe tenderness, and varying amount of vision loss. We report
      an uncommon presentation of posterior scleritis in a young male child. The
      patient presented with decreased vision and extraocular and intraocular
      inflammatory signs in the left eye. Fundus examination showed disk and macular
      edema with a T-sign on B-scan ultrasound. The patient showed good response to
      oral steroids with resolution of inflammation and recovery of vision.

PMID- 25390706
TI  - Occult maculopathy.
AB  - PURPOSE: To report a case of bilateral decrease in central vision with almost
      normal fundus examination. METHODS: A 50-year-old white man with central visual
      loss followed since 2006 with detailed ophthalmologic examinations and ancillary
      tests, including autoimmune and antiretinal antibody analyses. RESULTS: Virtually
      normal ophthalmoscopic examination, fluorescein and indocyanine green
      angiography, autofluorescence, red-free fundus pattern, and peripheral visual
      field testing. Abnormalities include reduced central macula thickness values
      (right and left eyes were 150 MUm and 146 MUm, respectively) on the spectral
      domain optical coherent tomography (normal value, 200-250 MUm) and decreased
      sensitivity of foveal eccentricities on multifocal electroretinogram. Antiretinal
      antibody tested positive for 27-kDa protein; and anti-optic nerve antibodies
      tested positive against 33-kDa, 35-kDa, and 46-kDa proteins. CONCLUSION: A
      central visual deficit with a nearly normal clinical picture and no family
      history are indicative of poorly defined entity called occult maculopathy. The
      role of antiretinal antibodies is unclear.

PMID- 25390707
TI  - Primary subretinal abscess caused by acanthamoeba: clinical and pathologic case
      report and review of the literature.
AB  - PURPOSE: To report the clinical and pathologic findings in a patient with a
      primary Acanthamoeba subretinal abscess. METHODS: A healthy 40-year-old man was
      evaluated and treated for a subretinal abscess. A subretinal aspirate was
      evaluated using hematoxylin-eosin stains and polymerase chain reaction. RESULTS:
      Results of the histologic examination of the subretinal aspirate demonstrated
      numerous Acanthamoeba cysts. The diagnosis was confirmed by polymerase chain
      reaction. The infection was treated with local and systemic antimicrobials. The
      visual acuity remained stable, and there was no local or systemic spread of the
      infection. CONCLUSION: To the authors' knowledge, this is the first biopsy-proven
      case of primary subretinal abscess because of Acanthamoeba. Acanthamoeba should
      be considered in the differential diagnosis of a subretinal abscess, even in the
      absence of systemic or corneal symptoms. Aggressive treatment can prevent serious
      ocular and systemic complications.

PMID- 25390708
TI  - A case of acute multifocal inner retinitis associated with nonspecific viral
      illness.
AB  - PURPOSE: To describe a patient with sudden unilateral loss of vision associated
      with white inner retinal lesions and a history of a nonspecific viral infection.
      METHODS: Case report. We reviewed the medical record and retinal angiogram of one
      patient. RESULTS: The patient presented with a sudden loss of visual acuity in
      the left eye. Fundus examination revealed multiple white inner retinal lesions
      and hyperemic optic disks in both eyes. Spontaneous improvement of visual acuity
      and resolution of the retinal lesions were noted over the ensuing weeks.
      CONCLUSION: Retinitis can present as a nonspecific response to various infectious
      agents. We herein report a case of acute multifocal inner retinitis associated
      with a nonspecific viral illness.

PMID- 25390709
TI  - Bacillus licheniformis as a cause of delayed-onset recurrent pseudophakic
      endophthalmitis-a rare case report.
AB  - PURPOSE: To report a case of delayed-onset recurrent pseudophakic endophthalmitis
      caused by Bacillus licheniformis. METHOD: Retrospective review of a case.
      RESULTS: A 30-year-old lady (s/p pseudophakia 10 years) presented with features
      of acute endophthalmitis and a vision of light perception in the left eye. She
      had received 15 intravitreal injections and systemic corticosteroids earlier for
      similar complaints. A core vitrectomy and intravitreal antibiotics injection
      improved her vision to 20/70, although the symptoms recurred a week later.
      Intraocular lens explantation with a repeat vitrectomy and intravitreal
      antibiotics was performed. The vitreous/aqueous fluid on both occasions grew B.
      licheniformis sensitive to fluoroquinolones, vancomycin, and gentamicin. One year
      after the second surgery, her vision was 20/30 with a quiet eye. CONCLUSION: This
      case shows that delayed-onset recurrent endophthalmitis after cataract extraction
      may be caused by Bacillus spp. and, despite sensitivity to most antibiotics, may
      require intraocular lens explantation for eradication of the infection.

PMID- 25390710
TI  - Diagnosis of a multicentric extranodal nasal-type natural killer T-cell lymphoma
      made with an anterior chamber tap.
AB  - PURPOSE: To report the case of an unusual multicentric Epstein-Barr virus (EBV)
      associated extranodal nasal-type natural killer T-cell lymphoma masquerading as
      unilateral panuveitis, diagnosed with an anterior chamber tap. METHODS: The
      clinical history and the morphological, immunohistochemical, and molecular
      features of a 51-year-old white man with left severe panuveitis were
      retrospectively evaluated. RESULTS: The patient initially presented with a 3
      month history of recalcitrant sinusitis and new onset of unilateral loss of
      vision. Clinical examination revealed right peripheral facial nerve palsy, severe
      panuveitis of the left eye, and nasopharyngeal obstruction. Anterior chamber
      aspirates were examined. The combination of the presence of small- to
      intermediate-size lymphocyte proliferation, moderate elevation of the interleukin
      10 level on cytokine profiling, and slightly positive polymerase chain reaction
      for EBV in the aqueous humor indicated an EBV-induced nasal-type natural killer T
      cell lymphoma. Transnasal biopsy revealed the presence of numerous irregular
      lymphoma cells with positive staining for CD3, CD56, EBV-encoded RNA in situ
      hybridization, and negative staining for CD4, CD8, and CD1a. Lumbar puncture,
      cerebral magnetic resonance imaging, thoracoabdominal computed tomography, and
      upper digestive tract endoscopy revealed meningeal, renal, adrenal, and digestive
      involvement. Massive hemorrhage of the upper digestive tract caused rapid death.
      CONCLUSION: Extranodal nasal-type natural killer T-cell lymphoma is a very
      uncommon disease that may present acutely, sometimes as pseudouveitis. Simple
      investigations such as anterior chamber aspirates for cytological examination,
      reinforced by cytokine profiling and viral polymerase chain reaction looking for
      EBV, may provide a rapid diagnosis, necessary given the poor prognosis of the
      disease. To our knowledge, and after extensive review of the literature, we did
      not find another case report diagnosing this entity by anterior chamber
      paracentesis.

PMID- 25390711
TI  - Correlation of fundus autofluorescence, spectral-domain optical coherence
      tomography, and microperimetry in late deferoxamine maculopathy.
AB  - PURPOSE: To describe long-term functional and morphologic retinal changes by
      deferoxamine, a chelating agent used to treat systemic iron overload. METHODS:
      Ophthalmologic examination of acute deferoxamine maculopathy and follow-up of 5
      years, using ophthalmologic examination, fluorescence angiography,
      electrophysiology, color vision testing, fundus image-correlated microperimetry,
      time-domain and spectral-domain optical coherence tomographies. The patient is a
      53-year old woman who presented with acute visual deterioration to 20/50 in the
      right eye, 20/60 in the left eye, and reduced color vision. She had been treated
      with deferoxamine for 6 months. The diagnosis of deferoxamine maculopathy was
      made, and the drug discontinued immediately. RESULTS: After 5 months, visual
      acuity was 20/25 bilaterally, but mottling of the retinal pigment epithelium
      (RPE) had developed. Five years later, visual acuity was 20/20 in both eyes.
      Fundus autofluorescence showed progressively clumped hyper- and hypofluorescence
      with larger areas of total RPE atrophy in the left eye. Spectral-domain optical
      coherence tomography visualized areas of RPE thickening, photoreceptor outer
      segment elongation, outer retinal tubulation, and outer retinal and RPE atrophy.
      Fundus image-correlated microperimetry showed relative central scotomas at the
      beginning, some of which recovered to normal light sensitivity, while others
      deteriorated to absolute scotomas. CONCLUSION: Although visual acuity had
      recovered after cessation of deferoxamine, functional and morphologic residues
      remained, which included disturbed color vision, central microscotomas, and
      progressive RPE and outer retinal degeneration.

PMID- 25390712
TI  - Macular infarction secondary to Staphylococcus epidermidis infection.
AB  - PURPOSE: To describe a patient with macular infarction caused by Staphylococcus
      epidermidis-induced endophthalmitis. METHODS: Case report. RESULTS: An 88-year
      old woman was referred to our clinic for endophthalmitis after cataract
      extraction. She was diagnosed to have an S. epidermidis infection. Her vision
      dropped from 20/50 to hand motions. During the course of her infection, she
      developed multiple multifocal branch retinal artery occlusions associated with
      absolute capillary nonperfusion centrally and was diagnosed with macular
      infarction. CONCLUSION: Although most commonly associated with aminoglycoside
      toxicity, macular infarction can occur after endophthalmitis treatment without
      the use of aminoglycosides.

PMID- 25390713
TI  - Simultaneous bilateral central retinal artery occlusion in churg-strauss
      syndrome.
AB  - PURPOSE: Retinal vascular abnormalities are rare in patients with Churg-Strauss
      syndrome. We present the findings in a patient with Churg-Strauss syndrome who
      developed bilateral central retinal artery occlusion simultaneously. METHODS:
      Case report. RESULTS: A 68-year-old Japanese man developed acute bilateral vision
      decrease to counting finger in the right eye and hand movements in the left eye.
      Ophthalmoscopic and angiographic examinations revealed a central retinal artery
      occlusion with choroidal circulatory disturbances in both the eyes. The patient
      had bronchial asthma, hypereosinophilia, radiographically determined migratory
      pulmonary opacities, and paranasal sinus abnormalities, thus fulfilling the
      American College of Rheumatology criteria for Churg-Strauss syndrome.
      Antineutrophil cytoplasmic antibody was absent. High-dose steroid therapy was
      used, but after 6 weeks, his visual acuity in the right eye did not improve, and
      the vision in the left eye was no light perception. Later, vitreous hemorrhage
      was developed in the left eye followed by retinal detachment associated with
      proliferative retinopathy. CONCLUSION: Bilateral central retinal artery occlusion
      can occur in patients with antineutrophil cytoplasmic antibody-negative Churg
      Strauss syndrome. The cause of the central retinal artery occlusion is not known,
      but consideration for prophylactic steroid therapy may be recommended in
      antineutrophil cytoplasmic antibody-negative cases to prevent potential visual
      loss.

PMID- 25390714
TI  - Intraocular bevacizumab levels 24 hours after intravitreal injection in a normal
      eye.
AB  - BACKGROUND: To determine intraocular levels of bevacizumab in a normal eye 24
      hours after the injection of bevacizumab into the vitreous cavity. METHODS: Fluid
      and tissue samples were analyzed for unbound bevacizumab levels using microsphere
      immunoassays. RESULTS: After a loading dose of 2.5 mg (0.1 mL) of bevacizumab,
      levels of unbound drug could be detected in all tissue extracts 24 hours after
      its injection. At least 60.2% of the injected bevacizumab could be accounted for
      in this study. Levels of 0.06 mg (2.4%) of bevacizumab were recorded in the
      choroid. CONCLUSION: At 24 hours, unbound bevacizumab levels can be detected at
      the level of the choroid. Therefore, bevacizumab can reach the site where
      choroidal neovascularization develops. This explains its reported therapeutic
      effect.

PMID- 25390715
TI  - Bilateral acute idiopathic frosted branch angiitis in a pregnant woman.
AB  - PURPOSE: To present a case of frosted branch angiitis in a pregnant woman.
      METHODS: A 27-week pregnant 18-year-old woman was presented with bilateral
      decreased visual acuity. Fundoscopy showed typical appearance of frosted branch
      angiitis. RESULTS: A good spontaneous clinical improvement was observed during
      systemic evaluation. No treatment was started. CONCLUSION: Frosted branch
      angiitis may be seen during pregnancy, without any associated underlying disease,
      and can be resolved without any intervention. The treatment may not be necessary
      for some cases.

PMID- 25390716
TI  - Resolution of refractory macular edema because of branch retinal vein occlusion
      after ozurdex implantation.
AB  - PURPOSE: To report a case of a woman with a branch vein occlusion and macular
      edema refractory to grid laser, intravitreal bevacizumab, pars plana vitrectomy
      with sheathotomy of the arteriovenous branch site, and intravitreal
      triamcinolone, who had complete resolution of fluid after injection of a
      dexamethasone intravitreal implant (DEX implant, Ozurdex; Allergan, Inc, Irvine,
      CA). METHODS: A 75-year-old woman with a branch vein occlusion and macular edema
      was treated with grid laser, intravitreal bevacizumab, pars plana vitrectomy with
      sheathotomy, and intravitreal triamcinolone. Neither edema nor vision improved.
      She was treated with an Ozurdex intravitreal implant. RESULTS: One month after
      Ozurdex intravitreal implantation, the patient's visual acuity and edema had
      improved dramatically. The macula remained flat until 5 months after injection
      when the edema returned and a second Ozurdex was injected. One month later, the
      macular edema was significantly less and visual acuity had improved to 20/50 with
      pinhole. CONCLUSION: Ozurdex may be effective in reducing macular edema because
      of a branch retinal vein occlusion in eyes refractory to multiple other
      treatments.

PMID- 25390717
TI  - Intravitreal bevacizumab followed by laser photocoagulation for retinal capillary
      hemanginoblastomas.
AB  - PURPOSE: To report a patient with retinal capillary hemangioblastomas associated
      with Von Hippel-Lindau syndrome who achieved long-term visual improvement with
      single intravitreal bevacizumab injection followed by laser photocoagulation.
      METHODS: Intravitreal bevacizumab injection was performed in a 17-year-old girl
      with bilateral multiple retinal capillary hemangioblastomas. Laser
      photocoagulation was then performed to augment the initial response to
      bevacizumab. The visual acuity, fundus photography, fundus fluorescein
      angiography, and ocular coherence tomography were obtained at each visit. The
      patient was followed-up for 3 years. RESULTS: Two weeks after injection, the
      macular edema and exudation significantly decreased with an improvement in the
      visual acuity. Laser photocoagulation performed 2 weeks after the intravitreal
      bevacizumab injection provided further regression of exudation and scarring of
      the hemangioblastomas. No further intervention was required, and the visual
      acuity returned to baseline at the third year of follow-up. CONCLUSION: Combined
      intravitreal bevacizumab with laser photocoagulation is a viable option in
      retinal capillary hemangioblastomas associated with Von Hippel-Lindau syndrome.

PMID- 25390718
TI  - Heavy silicone oil (densiron) and supine position in the management of massive
      suprachoroidal hemorrhage: use of heavy silicone for suprachoroidal hemorrhage.
AB  - PURPOSE: To describe a case of massive suprachoroidal hemorrhage after a
      phacoemulsification managed with pars plana vitrectomy, heavy silicone oil
      (Densiron), and supine position. METHODS: Report of a 69-year-old woman with
      systemic hypertension and under antiplatelet treatment who developed a massive
      suprachoroidal hemorrhage. RESULTS: The patient underwent a pars plana vitrectomy
      and heavy oil endotamponade combined with 3 radial sclerotomies to drain the
      suprachoroidal blood. Two months after this surgery, the retina remains attached
      and visual acuity is 3/60 with aphakia and half of the vitreous cavity filled
      with Densiron. CONCLUSION: Pars plana vitrectomy and Densiron endotamponade with
      supine position can represent a good surgical option in such a dramatic case as a
      suprachoroidal hemorrhage. Long-term heavy silicone oil endotamponade cannot be
      advised in these cases.

PMID- 25390719
TI  - Evolution and management of macular tractional detachment with a macular hole in
      the presence of nonperfused hemiretinal vein occlusion.
AB  - PURPOSE: We report iatrogenic occurrence of a macular tractional retinal
      detachment with macular hole in nonperfused hemiretinal vein occlusion and
      describe its management with vitrectomy, without internal limiting membrane
      peeling. METHODS: A 40-year-old man with diabetes was treated with scatter
      photocoagulation for a unilateral nonperfused hemiretinal vein occlusion with a
      florid neovascularization at optic disk and best-corrected visual acuity of
      20/200. A month later, he developed an extensive tractional detachment of the
      posterior pole with a macular hole, with further drop in vision to hand motions.
      Pars plana vitrectomy was performed with complete removal of the tractional
      membranes, followed by silicone oil tamponade. No attempt was made to peel the
      internal limiting membrane. RESULTS: Postoperatively, the retina was reattached
      with closure of the macular hole. Silicone oil was removed after 4 months. The
      anatomic outcomes were maintained for more than a year postoperatively. The
      patient's best-corrected visual acuity recovered to 20/80 by the final follow-up
      visit. CONCLUSION: Scatter photocoagulation in retinal vein occlusion is a
      potentially hazardous intervention in the presence of preexisting fibrous tissue.
      Macular hole, when coexistent with a tractional retinal detachment, can be closed
      with vitrectomy and release of traction, without an intentional attempt at hole
      closure. Good anatomic and visual outcomes are possible with early intervention.

PMID- 25390720
TI  - Sudden visual loss after intravitreal triamcinolone.
AB  - PURPOSE: To report a case of sudden loss of vision after intravitreal
      triamcinolone for the management of cystoid macular edema secondary to a central
      retinal vein occlusion with subsequent development of nonarteritic anterior
      ischemic optic neuropathy. METHOD: Retrospective case report. CONCLUSION: The
      pathophysiology of nonarteritic anterior ischemic optic neuropathy (NAION) still
      remains controversial. Our report does not allow any conclusion about a direct
      causal relationship, however we postulate a contributory role of intrvitreal
      triamcinolone in the development of NAION in our patient.

PMID- 25390721
TI  - Retinitis pigmentosa associated with progressive hemifacial atrophy (parry
      romberg syndrome).
AB  - PURPOSE: The Parry-Romberg syndrome, or progressive hemifacial atrophy, is a
      slowly progressive marked facial deformity because of atrophy of subcutaneous fat
      and skin, cartilage, and bone wasting. Various ocular findings may be present in
      approximately 40% of cases of progressive hemifacial atrophy. We describe a novel
      case of a 42-year-old woman with progressive hemifacial atrophy and bilateral
      retinal dystrophy consistent with retinitis pigmentosa. METHODS: Case report and
      literature review. RESULTS: Clinical features, fundus photographs, visual fields,
      and electroretinographic findings are reported. CONCLUSION: Progressive
      hemifacial atrophy can occur with retinitis pigmentosa.

PMID- 25390722
TI  - Successful treatment of ophthalmomyiasis interna posterior with ivermectin.
AB  - PURPOSE: To report the first successful medical treatment of ophthalmomyiasis
      interna posterior without associated surgical treatment. METHOD: Interventional
      case report. The patient is an 11-year-old boy with panuveitis and neuroretinitis
      associated with a pathognomonic presentation of ophthalmomyiasis interna
      posterior in which the larva could not be identified. The patient received
      medical treatment with a single oral dose of ivermectin of 200 mg/kg followed by
      systemic steroid therapy without associated surgical extraction of the larva via
      pars plana vitrectomy or laser photocoagulation. RESULTS: Anterior and posterior
      uveitis resolution, reversal of neuroretinitis, and visual acuity improvement.
      CONCLUSION: Medical treatment with ivermectin can be considered as primary
      therapeutic modality in ophthalmomyiasis interna posterior.

PMID- 25390723
TI  - Bilateral presumed ischemic optic neuropathy secondary to cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
AB  - PURPOSE: To report a case of bilateral ischemic optic neuropathy (ION) secondary
      to hypoperfusion of the optic nerve because of cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy, an uncommon
      condition causing stepwise subcortical small vessel infarcts because of arterial
      wall rigidity, loss of autoregulation, and hypoperfusion. METHODS: We describe
      the ophthalmological presentation of this case including fluorescein angiography
      and kinetic perimetry. RESULTS: Cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy is an increasingly recognized
      condition with significant neurological sequelae. This case demonstrates the
      potential for secondary visual loss because of optic nerve hypoperfusion, and the
      literature confirms this mechanism of injury for both the optic nerve and retina.
      Retinal screening may add evidence toward the diagnosis in visually asymptomatic
      patients. Because there is no treatment for the condition, management is
      symptomatic only but involves psychological support and genetic counseling.
      CONCLUSION: We propose that cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy be added to the list of potential
      differential diagnoses for ION in young patients.

PMID- 25390724
TI  - An in vivo morphologic comparison of retinal neovascularization in sickle cell
      and diabetic retinopathy.
AB  - PURPOSE: To analyze the in vivo morphology of the sea fan in proliferative sickle
      cell retinopathy and compare it with the neovascularization in proliferative
      diabetic retinopathy. METHODS: Brief case report of spectral-domain optical
      coherence tomography imaging of a sea fan in a patient with sickle cell anemia
      and newly diagnosed proliferative sickle cell retinopathy, and morphologic
      comparison with spectral-domain optical coherence tomography imaging of a
      neovascular membrane in a diabetic patient with proliferative diabetic
      retinopathy. RESULTS: Spectral-domain optical coherence tomography imaging
      revealed that the sea fan is a thicker caliber preretinal fibrovascular membrane
      involving primarily the retinal nerve fiber and ganglion cell layers. The
      diabetic membrane has more vitreous adhesions, and it is more closely intertwined
      with the retina, involving all the retinal layers down to the outer plexiform
      layer. CONCLUSION: Spectral-domain optical coherence tomography imaging
      identified important in vivo morphologic differences between neovascularization
      in proliferative sickle cell retinopathy and proliferative diabetic retinopathy.
      These differences were consistent with previous histological studies and may
      explain the increased risk of tractional retinal detachment in patients with
      diabetes.

PMID- 25390725
TI  - Posterior scleritis resembling acute retinal necrosis syndrome.
AB  - PURPOSE: To report a challenging diagnosis of posterior scleritis in a patient
      with features of retinal necrosis. METHODS: Single observational case report.
      RESULTS: A 74-year-old man presented with atypical anterior scleritis in the left
      eye. Funduscopy showed subretinal inflammatory infiltration resembling acute
      retinal necrosis. The patient was treated with indomethacin, with resolution of
      the process. CONCLUSION: Typical signs of posterior scleritis include serous
      retinal detachment and choroidal folds in the posterior pole. Nonetheless, an
      atypical presentation can also occur, with peripheral whitish or subretinal
      inflammatory infiltrate, serous retinal detachment, and hemorrhages, resembling
      an acute retinal necrosis syndrome.

PMID- 25390726
TI  - Immune-recovery posterior uveitis associated with inactive isolated toxoplasmic
      retinochoroiditis in a patient with human immunodeficiency virus.
AB  - PURPOSE: To report a case of severe panuveitis in a patient with human
      immunodeficiency virus that developed after inactivation of toxoplasmic
      retinochoroiditis. The patient also developed cerebral toxoplasmosis. METHODS: A
      patient with human immunodeficiency virus who developed immune-recovery posterior
      uveitis in the context of inactive toxoplasmic retinochoroiditis underwent
      complete ophthalmologic evaluation, polymerase chain reaction of the aqueous
      humor, diagnostic vitrectomy, and cerebral ancillary testing. RESULTS: Polymerase
      chain reaction-confirmed toxoplasmic retinochoroiditis healed with appropriate
      treatment, but 2 months later coinciding with systemic immune restoration, the
      brain lesions worsened and immune-recovery panuveitis caused decreased visual
      acuity. Diagnostic vitrectomy confirmed only inflammatory cells. CONCLUSION:
      Immune-recovery panuveitis caused by cytomegalovirus retinitis is well
      documented, but we found only one published case caused by toxoplasma. Immune
      recovery panuveitis should not be ruled out despite the absence of previous
      cytomegalovirus retinitis. A patient with human immunodeficiency virus who has
      had an intraocular opportunistic infection, despite resolution, must be followed
      up by an ophthalmologist in collaboration with an infectious disease specialist
      to prevent blindness.

PMID- 25390727
TI  - Lamellar macular hole after ranibizumab in a patient with neovascular age-related
      macular degeneration and vitreomacular adhesion.
AB  - PURPOSE: To report a case of formation of lamellar macular hole after ranibizumab
      in a patient with neovascular age-related macular degeneration and vitreomacular
      adhesion. METHODS: A 76-year-old man with neovascular age-related macular
      degeneration and vitreomacular adhesion was studied by biomicroscopy, fluorescein
      angiography, and optical coherence tomography and was treated with intravitreal
      ranibizumab. RESULTS: The neovascular membrane regressed and the patient
      developed lamellar macular hole when seen 1 month after the ranibizumab
      injection. CONCLUSION: Persistent vitreomacular traction along with the decrease
      in retinal edema after intravitreal ranibizumab could have contributed to the
      formation of lamellar macular hole. Thus, in cases with retinal edema and
      vitreomacular adhesion, this event after anti-vascular endothelial growth factor
      therapy should be considered, especially if vision does not improve despite
      resolution of edema.

PMID- 25390728
TI  - Pulsed intravenous cyclophosphamide for sle retinal vasculitis.
AB  - PURPOSE: To report a case of systemic lupus erythematosus vaso-occlusive
      retinopathy with severe visual loss treated with intravenous pulsed
      cyclophosphamide. METHODS: Retrospective interventional case report. RESULTS: A
      20-year-old Cambodian woman with newly diagnosed systemic lupus erythematosus
      presented with acute visual loss. Fluorescein fundus angiography demonstrated
      occlusive retinal vasculitis. Treatment with pulsed intravenous cyclophosphamide,
      intravenous methylprednisolone, and anticoagulation resulted in recovery of
      vision from count fingers to 6/6 in both eyes. CONCLUSION: Early aggressive
      immunosuppression and anticoagulation for systemic lupus erythematosus retinal
      vasculitis can be beneficial in preventing disease progression and restoring
      vision. Further studies are needed to compare dosage regimens.

PMID- 25390729
TI  - Apical atrophy of retinal pigment epithelial detachments in central serous
      chorioretinopathy.
AB  - PURPOSE: To describe a presumed precursor stage of central serous
      chorioretinopathy (CSC). METHODS: Two patients were identified during follow-up
      study of patients with CSC or CSC-related conditions. Two patients first seen
      with retinal pigment epithelial detachment subsequently developed findings
      compatible with CSC. RESULTS: A juxtafoveal retinal pigment epithelial detachment
      with apical atrophy of the retinal pigment epithelium with corresponding severe
      attenuation of the pigmentation of the retinal pigment epithelium was observed in
      both patients. One of the patients presented with a serous neurosensory retinal
      detachment with smokestack leakage 7 years after first being seen. The other
      patient was never seen with a neurosensory detachment. CONCLUSION: Isolated
      pigment epithelial detachment with apical retinal pigment epithelial atrophy may
      represent a precursor stage of CSC.

PMID- 25390730
TI  - The use of a vascular endothelial growth factor inhibitor (ranibizumab) in
      macular edema due to eales disease.
AB  - PURPOSE: To report the results of intravitreal use of ranibizumab in a patient
      with macular edema due to Eales disease. METHOD: This was an open-label, Phase 1,
      6-month study of the safety and efficacy of intravitreally administered
      ranibizumab in patients with macular edema due to Eales disease. A single patient
      was eligible for the study during the 2 years of recruitment. She received 3
      monthly intravitreal injections of 0.5 mg of ranibizumab for 3 months. At each of
      her monthly visits during the 6-month study, she was evaluated with a full ocular
      examination and optical coherence tomography imaging of the macula. Primary
      outcome measure was change in optical coherence tomography central subfield
      thickness at 6 months. RESULTS: The central macular thickness as measured on
      optical coherence tomography reduced from 269 MUm at baseline to 186 MUm at 3
      months. This reduction was transient with subsequent increase to 262 MUm at the
      conclusion of the study at 6 months. CONCLUSION: Ranibizumab use led to transient
      resolution of macular edema at 3 months; however, this reduction in edema was not
      sustained.

PMID- 25390731
TI  - Bilateral macular hole after anti-vascular endothelial growth factor therapy in a
      patient with exudative age-related macular degeneration.
AB  - PURPOSE: To report a case of bilateral nonsequential macular holes that developed
      after intravitreal ranibizumab therapy for treatment of exudative age-related
      macular degeneration. METHODS: A 76-year-old man presented with sudden vision
      loss in the right eye initially followed by the left eye 1 year later. Initial
      fundoscopic examination showed a subretinal hemorrhage in the right eye and dry
      macular degeneration in the left eye. Initial optical coherence tomography and
      fluorescein angiogram confirmed the diagnosis of subfoveal choroidal
      neovascularization in the right eye. There was no evidence of vitreofoveal
      traction. The patient was treated with intravitreal injections of ranibizumab
      (0.5 mg). One year later, choroidal neovascularization developed in his left eye
      as well. RESULTS: After choroidal neovascularization regression, full-thickness
      macular holes were observed in both eyes. Pars plana vitrectomy with internal
      limiting membrane removal was performed in both eyes. Anatomic closure of the
      macular hole in the left eye without significant vision improvement occurred but
      the right macular hole remained open despite the surgery. CONCLUSION: Exudative
      age-related macular degeneration can be a precursor to macular hole formation.

PMID- 25390732
TI  - Chronic central serous chorioretinopathy responsive to rifampin.
AB  - PURPOSE: The purpose of this was to describe the clinical improvement of chronic
      central serous chorioretinopathy in a patient treated with rifampin for
      tuberculosis. METHODS: A 54-year-old Hispanic man with a distant history of
      pulmonary tuberculosis presented with reduced vision in the right greater than
      left eye for over 1 year. He had diffuse chorioretinopathy in both eyes and a
      serous retinal detachment in his right eye. The findings were most consistent
      with chronic central serous chorioretinopathy, although tuberculosis -related
      choroiditis could not be excluded. Treatment with multidrug antituberculosis
      medications, including rifampin, resulted in the reduction in leakage and
      resolution of subretinal fluid. Fluid recurred on cessation of all medications
      and resolved again with retreatment. Monotherapy with rifampin maintained the
      absence of fluid. DISCUSSION: This case represents the first report of chronic
      central serous chorioretinopathy responding to systemic therapy with rifampin. We
      hypothesize that the clinical response observed is secondary to induction of
      cytochrome P450 with increased hepatic metabolism of endogenous corticosteroids
      and a reduction in systemic cortisol levels.

PMID- 25390733
TI  - Retinal cases & brief reports 2011 scientific reviewers.

PMID- 25390734
TI  - Cigarette smoking impairs human pulmonary immunity to Mycobacterium tuberculosis.
AB  - RATIONALE: Cigarette smoking is linked to important aspects of tuberculosis, such
      as susceptibility to infection, disease reactivation, mortality, transmission,
      and persistent infectiousness. The mechanistic basis for this remains poorly
      understood. OBJECTIVES: To compare the functional impairment seen in human
      alveolar macrophages (AM) from nonsmokers, smokers, and ex-smokers after
      infection with Mycobacterium tuberculosis (Mtb). METHODS: AM were acquired at
      bronchoscopy, and number and viability from smoking donors were compared with
      nonsmoking donors. AM were challenged in vitro with Mtb and intracellular
      bacterial viability was measured. Cytokine secretion was measured 24 hours
      postinfection by ELISA. Previously we determined the frequency of CD4(+)FoxP3(+)
      T cells in the presence or absence of allogeneic AM, and data were reanalyzed to
      separate the patient subjects according to smoking status. MEASUREMENTS AND MAIN
      RESULTS: There were significantly more AM from smokers compared with nonsmokers
      or ex-smokers (P < 0.01). AM from smokers could not control intracellular Mtb
      growth. Nonsmokers' AM generated significantly more tumor necrosis factor (TNF)
      alpha, IFN-gamma, and IL-1beta after Mtb infection compared with uninfected AM (P
      < 0.05). However, Mtb-infected AM from smokers did not secrete significantly more
      TNF-alpha, IFN-gamma, and IL-1beta compared with uninfected smokers' AM. AM taken
      from ex-smokers also failed to secrete significantly increased TNF-alpha, IFN
      gamma, and IL-1beta after Mtb infection. Both smokers' and nonsmokers' AM induced
      FoxP3(+) T regulatory cell phenotype responses in allogeneic admixed T cells
      (>4.8 fold; P < 0.05). Even after Mtb infection, AM continued to drive this
      regulatory phenotype. CONCLUSIONS: In smokers, the pulmonary compartment has a
      number of macrophage-specific immune impairments that provide some mechanistic
      explanations whereby cigarette smoking renders a patient susceptible to
      tuberculosis infection and disease.

PMID- 25390736
TI  - An electromyographic-based test for estimating neuromuscular fatigue during
      incremental treadmill running.
AB  - The purposes of the present study were two fold: (1) to determine if the model
      used for estimating the physical working capacity at the fatigue threshold
      (PWCFT) from electromyographic (EMG) amplitude data during incremental cycle
      ergometry could be applied to treadmill running to derive a new neuromuscular
      fatigue threshold for running, and (2) to compare the running velocities
      associated with the PWCFT, ventilatory threshold (VT), and respiratory
      compensation point (RCP). Fifteen college-aged subjects (21.5 +/- 1.3 y, 68.7 +/-
      10.5 kg, 175.9 +/- 6.7 cm) performed an incremental treadmill test to exhaustion
      with bipolar surface EMG signals recorded from the vastus lateralis. There were
      significant (p < 0.05) mean differences in running velocities between the VT
      (11.3 +/- 1.3 km h(-1)) and PWCFT (14.0 +/- 2.3 km h(-1)), VT and RCP (14.0 +/-
      1.8 km h(-1)), but not the PWCFT and RCP. The findings of the present study
      indicated that the PWCFT model could be applied to a single continuous,
      incremental treadmill test to estimate the maximal running velocity that can be
      maintained prior to the onset of neuromuscular fatigue. In addition, these
      findings suggested that the PWCFT, like the RCP, may be used to differentiate the
      heavy from severe domains of exercise intensity.

PMID- 25390735
TI  - The gut microbiota modulates glycaemic control and serum metabolite profiles in
      non-obese diabetic mice.
AB  - Islet autoimmunity in children who later progress to type 1 diabetes is preceded
      by dysregulated serum metabolite profiles, but the origin of these metabolic
      changes is unknown. The gut microbiota affects host metabolism and changes in its
      composition contribute to several immune-mediated diseases; however, it is not
      known whether the gut microbiota is involved in the early metabolic disturbances
      in progression to type 1 diabetes. We rederived non-obese diabetic (NOD) mice as
      germ free to explore the potential role of the gut microbiota in the development
      of diabetic autoimmunity and to directly investigate whether the metabolic
      profiles associated with the development of type 1 diabetes can be modulated by
      the gut microbiota. The absence of a gut microbiota in NOD mice did not affect
      the overall diabetes incidence but resulted in increased insulitis and levels of
      interferon gamma and interleukin 12; these changes were counterbalanced by
      improved peripheral glucose metabolism. Furthermore, we observed a markedly
      increased variation in blood glucose levels in the absence of a microbiota in NOD
      mice that did not progress to diabetes. Additionally, germ-free NOD mice had a
      metabolite profile similar to that of pre-diabetic children. Our data suggest
      that germ-free NOD mice have reduced glycaemic control and dysregulated
      immunologic and metabolic responses. 

PMID- 25390737
TI  - Relationship between cranial mechanics and dysmorphic dentofacial
      characteristics: a cross-sectional study.
AB  - AIMS: The aim of the present study was to evaluate if cranial dysfunctions felt
      by osteopaths could correlate with sagittal dysmorphologies diagnosed by
      orthodontists, using cephalometric traces in the sagittal plane. Metholology: One
      hundred and six children between 6 and 12 years old (42 boys and 64 girls) were
      tested by an osteopath to determine if the cranial movement felt was considered
      to be eased in flexion or extension. To test reproducibility intra-operator, 27
      randomly selected subjects were tested twice, at a one-month interval by the same
      osteopath before the start of their orthodontic treatment. These tests were then
      correlated with a cephalometric analysis of the sagittal plane to determine what
      type of dysmorphology existed, if any, as well as the angle of the spheno
      occipital synchondrosis (SOS). RESULTS: Practitioners systematically found more
      cranial movement in extension for all the bones in patients in skeletal class II
      than in the others. Similarly, they systematically found more cranial movement in
      flexion in patients in skeletal class III than in the other skeletal classes.
      However, there was no significant difference found in SOS angulation between
      skeletal classes I, II, and III. DISCUSSION: This study tends to confirm the
      correlation, described previously by orthodontists, between the mobility of the
      bones of the cranial vault and dysmorphic dentofacial characteristics in the
      sagittal plane. Anomalies during development could lead to the typical cranial
      characteristics of flexion or extension. As such, these situations could be
      related to skeletal classes III and II respectively.

PMID- 25390738
TI  - Marketing to physicians in a digital world.
AB  - Pharmaceutical marketing can lead to overdiagnosis, overtreatment, and overuse of
      medications. Digital advertising creates new pathways for reaching physicians,
      allowing delivery of marketing messages at the point of care, when clinical
      decisions are being made. 

PMID- 25390739
TI  - High-cost generic drugs--implications for patients and policymakers.
AB  - Some older generic drugs have become very expensive, owing to factors including
      drug shortages, supply disruptions, and consolidations in the generic-drug
      industry. But generics manufacturers that legally obtain a market monopoly can
      also unilaterally raise prices. 

PMID- 25390740
TI  - Monocarboxylate transporter 1 deficiency and ketone utilization.
AB  - Ketoacidosis is a potentially lethal condition caused by the imbalance between
      hepatic production and extrahepatic utilization of ketone bodies. We performed
      exome sequencing in a patient with recurrent, severe ketoacidosis and identified
      a homozygous frameshift mutation in the gene encoding monocarboxylate transporter
      1 (SLC16A1, also called MCT1). Genetic analysis in 96 patients suspected of
      having ketolytic defects yielded seven additional inactivating mutations in MCT1,
      both homozygous and heterozygous. Mutational status was found to be correlated
      with ketoacidosis severity, MCT1 protein levels, and transport capacity. Thus,
      MCT1 deficiency is a novel cause of profound ketoacidosis; the present work
      suggests that MCT1-mediated ketone-body transport is needed to maintain acid-base
      balance. 

PMID- 25390741
TI  - The alpha-thalassemias.
AB  - More than 100 varieties of alpha-thalassemia have been identified. Their
      geographic distribution and the challenges associated with screening, diagnosis,
      and management suggest that alpha-thalassemias should have a higher priority on
      global public health agendas. 

PMID- 25390742
TI  - Images in clinical medicine: Gas gangrene of a prosthetic hip.

PMID- 25390743
TI  - Case records of the Massachusetts General Hospital. Case 35-2014: a 31-year-old
      woman with fevers, chest pain, and a history of HCV infection and substance-use
      disorder.
AB  - A 31-year-old woman with substance-use disorder was admitted to this hospital
      because of fevers and chest pain. CT of the chest revealed multiple thick-walled
      nodular opacities throughout both lungs. Diagnostic tests were performed, and
      management decisions were made. 

PMID- 25390744
TI  - Rapid evolution of combination therapy in melanoma.

PMID- 25390745
TI  - Monocarboxylate transport matters.

PMID- 25390746
TI  - Cholesterol metabolism and immunity.
AB  - A study in mice implicates a cholesterol derivative in damping down the
      inflammatory response mediated by interleukin-1beta and explaining, at least in
      part, the immunosuppressive effect of type I interferon, which is used in the
      treatment of multiple sclerosis. 

PMID- 25390747
TI  - Expectation management.
AB  - As physicians transform observed frequencies from studies into predicted
      probabilities for a given patient, we generally fail to consider that the
      predictions we utter about a given therapeutic intervention are themselves part
      of the intervention. 

PMID- 25390748
TI  - Niacin for reduction of cardiovascular risk.

PMID- 25390749
TI  - Niacin for reduction of cardiovascular risk.

PMID- 25390750
TI  - Niacin for reduction of cardiovascular risk.

PMID- 25390751
TI  - Niacin for reduction of cardiovascular risk.

PMID- 25390752
TI  - Niacin for reduction of cardiovascular risk.

PMID- 25390753
TI  - Niacin for reduction of cardiovascular risk.

PMID- 25390754
TI  - Niacin for reduction of cardiovascular risk.

PMID- 25390755
TI  - Spread of artemisinin resistance in malaria.

PMID- 25390756
TI  - Epidemiology of blunt head trauma in children in U.S. emergency departments.
AB  - Among more than 43,000 children treated in 25 emergency departments for blunt
      head trauma, traumatic brain injury was identified on CT scan in 7% of the
      patients. Falls were the most frequent injury mechanism for children under the
      age of 12 years. 

PMID- 25390758
TI  - Images in clinical medicine: Rotation of the liver in pneumoperitoneum.

PMID- 25390759
TI  - Clinical decisions: Screening an asymptomatic person for genetic risk--polling
      results.

PMID- 25390760
TI  - Automated Image Processing for Spatially Resolved Analysis of Lipid Droplets in
      Cultured 3T3-L1 Adipocytes.
AB  - Cellular hypertrophy of adipose tissue underlies many of the proposed
      proinflammatory mechanisms for obesity-related diseases. Adipose hypertrophy
      results from an accumulation of esterified lipids (triglycerides) into membrane
      enclosed intracellular lipid droplets (LDs). The coupling between adipocyte
      metabolism and LD morphology could be exploited to investigate biochemical
      regulation of lipid pathways by monitoring the dynamics of LDs. This article
      describes an image processing method to identify LDs based on several distinctive
      optical and morphological characteristics of these cellular bodies as they appear
      under bright-field. The algorithm was developed against images of 3T3-L1
      preadipocyte cultures induced to differentiate into adipocytes. We show that the
      calculated lipid volumes are in excellent agreement with enzymatic assay data on
      total intracellular triglyceride content. We also demonstrate that the image
      processing method can efficiently characterize the highly heterogeneous spatial
      distribution of LDs in a culture by showing that differentiation occurs in
      distinct clusters separated by regions of nearly undifferentiated cells.
      Prospectively, the LD detection method described in this work could be applied to
      time-lapse data collected with simple visible light microscopy equipment to
      quantitatively investigate LD dynamics. 

PMID- 25390761
TI  - Endocan, a novel marker of endothelial dysfunction in patients with essential
      hypertension: comparative effects of amlodipine and valsartan.
AB  - Vascular inflammation plays an important role in the pathophysiology of
      hypertension and high levels of endocan may reflect ongoing vascular inflammation
      in hypertensive patients. In the present hypothesis-generating study, we aimed at
      investigating the comparative effects of amlodipine and valsartan on endocan
      levels in newly diagnosed hypertensive patients. The study population consisted
      of 37 untreated hypertensive patients who were randomized to the two treatment
      arms. After baseline assessment, each patient was randomly allocated to either 10
      mg daily of amlodipine (n = 18, 7 males) or 160 mg daily of valsartan (n = 19, 3
      males) and treated for a 3-month period. Sphygmomanometric blood pressure (BP)
      and serum endocan were measured before and every 2 weeks during drug treatment.
      There was no statistically significant difference between the two treatment arms
      as far as baseline socio-demographic and clinical characteristics are concerned.
      After a 3-month treatment period, systolic and diastolic BP values significantly
      reduced by antihypertensive treatment (p < 0.001). Furthermore, endocan levels
      were significantly decreased in both treatment arms (p < 0.05). However,
      amlodipine caused a greater percent decrease in circulating endocan levels
      compared with valsartan at the end of the treatment period. Both drugs reduced
      high sensitivity C-reactive protein values. However, the statistical significant
      difference vs baseline was achieved only in the group treated with amlodipine. No
      correlation was found between endocan plasma levels and BP reduction. The results
      of this hypothesis-generating study suggest that amlodipine and valsartan
      decrease endocan levels in newly diagnosed hypertensive patients. The effects,
      which are more evident with amlodipine, may contribute to the anti-inflammatory
      effects exerted by the two drugs on the vascular target.

PMID- 25390762
TI  - Spatial and temporal patterns of avian paramyxovirus-1 outbreaks in double
      crested cormorants (Phalacrocorax auritus) in the USA.
AB  - Morbidity and mortality events caused by avian paramyxovirus-1 (APMV-1) in Double
      crested Cormorant (DCCO; Phalacrocorax auritus) nesting colonies in the US and
      Canada have been sporadically documented in the literature. We describe APMV-1
      associated outbreaks in DCCO in the US from the first reported occurrence in 1992
      through 2012. The frequency of APMV-1 outbreaks has increased in the US over the
      last decade, but the majority of events have continued to occur in DCCO colonies
      in the Midwestern states. Although morbidity and mortality in conesting species
      has been frequently reported during DCCO APMV-1 outbreaks, our results suggest
      that isolation of APMV-1 is uncommon in species other than DCCO during APMV-1
      outbreaks and that the cause of mortality in other species is associated with
      other pathogens. Populations of DCCO do not appear to have been significantly
      affected by this disease; however, because at least 65% of the APMV-1 outbreaks
      in DCCO in the US have involved APMV-1 strains classified as virulent to poultry
      (virulent Newcastle disease virus), its persistence and increased occurrence in
      DCCO warrants continued research and surveillance.

PMID- 25390763
TI  - Coinfection and vertical transmission of Brucella and Morbillivirus in a neonatal
      sperm whale (Physeter macrocephalus) in Hawaii, USA.
AB  - The viral genus Morbillivirus and the bacterial genus Brucella have emerged as
      important groups of pathogens that are known to affect cetacean health on a
      global scale, but neither pathogen has previously been reported from endangered
      sperm whales (Physeter macrocephalus). A female neonate sperm whale stranded
      alive and died near Laie on the island of Oahu, Hawaii, US, in May of 2011.
      Congestion of the cerebrum and enlarged lymph nodes were noted on the gross
      necropsy. Microscopic findings included lymphoid depletion, chronic meningitis,
      and pneumonia, suggesting an in utero infection. Cerebrum, lung, umbilicus, and
      select lymph nodes (tracheobronchial and mediastinal) were positive for Brucella
      by PCR. Brucella sp. was also cultured from the cerebrum and from mediastinal and
      tracheobronchial lymph nodes. Twelve different tissues were screened for
      Morbillivirus by reverse-transcriptase (RT)-PCR and select tissues by
      immunohistochemistry, but only the tracheobronchial lymph node and spleen were
      positive by RT-PCR. Pathologic findings observed were likely a result of
      Brucella, but Morbillivirus may have played a key role in immune suppression of
      the mother and calf. The in utero infection in this individual strongly supports
      vertical transmission of both pathogens.

PMID- 25390764
TI  - Necropsy findings in 62 opportunistically collected free-ranging moose (Alces
      alces) from Minnesota, USA (2003-13).
AB  - The Minnesota, US moose population has declined dramatically since the 1990s. All
      54 carcasses of moose that died of unknown cause or were euthanized by gun shot
      by tribal or Department of Natural Resources personnel because of perceived signs
      of illness between 2003 and 2013 and eight carcasses of moose that died from
      vehicular accidents between 2009 and 2013 were submitted to the Minnesota
      Veterinary Diagnostic Laboratory and included in our study. The majority of the
      animals were underweight or cachectic (n = 53; 85%). Neural migration presumably
      by Parelaphostrongylus tenuis was a common finding (n = 28; 45%). Moderate to
      marked Dermacentor albipictus ("winter tick") ectoparasitism with widespread
      alopecia was the cause or a contributing cause of death in 14 (23%) cases in
      which grossly apparent anemia was associated with exhaustion of hepatic iron
      stores. Hepatic lesions associated with Fascioloides magna were common (n = 37;
      60%) but were unlikely to be the cause of death. Environmental factors favoring
      winter tick survival, habitat expansion of white-tailed deer (Odocoileus
      virginianus), and the survival of terrestrial and aquatic snails (serving as
      intermediate hosts for P. tenuis and F. magna), might contribute to the seemingly
      severe parasitic burden in Minnesota's moose population.

PMID- 25390765
TI  - Influence of land use and climate on Salmonella carrier status in the small
      Indian mongoose (Herpestes auropunctatus) in Grenada, West Indies.
AB  - Invasive mammals can be important reservoirs for human pathogens. A recent study
      showed that 12% of mongooses carried Salmonella spp. in their large intestines.
      We investigated whether anthropogenic, environmental and climatic variables
      predicted Salmonella status in mongooses (Herpestes auropunctatus) in Grenada.
      Using multivariate logistic regression and contingency table analysis, we found
      that increased human density, decreased distance from roads, and low monthly
      precipitation were associated with increased probability of Salmonella carriage.
      Areas with higher human density likely support a higher abundance of mongooses
      because of greater food availability. These areas also are a likely source for
      infection to mongooses due to high densities of livestock and rodents shedding
      Salmonella. The higher probability of Salmonella carriage in mongooses during
      drier months and closer to roadsides is likely due to water drainage patterns and
      limited water availability. Although the overall prevalence of Salmonella in
      mongooses was moderate, the strong patterns of ecologic correlates, combined with
      the high density of mongooses throughout Grenada suggest that the small Indian
      mongoose could be a useful sentinel for Salmonella surveillance. Its affinity for
      human-associated habitats suggests that the small Indian mongoose is also a risk
      factor in the maintenance and possible spread of Salmonella species to humans and
      livestock in Grenada.

PMID- 25390766
TI  - DNA lesion can facilitate base ionization: vertical ionization energies of
      aqueous 8-oxoguanine and its nucleoside and nucleotide.
AB  - 8-Oxoguanine is one of the key products of indirect radiation damage to DNA by
      reactive oxygen species. Here, we describe ionization of this damaged nucleobase
      and the corresponding nucleoside and nucleotide in aqueous phase, modeled by the
      nonequilibrium polarizable continuum model, establishing their lowest vertical
      ionization energies of 6.8-7.0 eV. We thus confirm that 8-oxoguanine has even
      lower ionization energy than the parental guanine, which is the canonical
      nucleobase with the lowest ionization energy. Therefore, it can act as a trap for
      the cationic hole formed by ionizing radiation and thus protect DNA from further
      radiation damage. We also model using time-dependent density functional theory
      and measure by liquid jet photoelectron spectroscopy the valence photoelectron
      spectrum of 8-oxoguanine in water. We show that the calculated higher lying
      ionization states match well the experiment which, however, is not sensitive
      enough to capture the electron signal corresponding to the lowest ionization
      process due to the low solubility of 8-oxoguanine in water. 

PMID- 25390767
TI  - Interventions for preventing or reducing domestic violence against pregnant
      women.
AB  - BACKGROUND: Domestic violence during pregnancy is a major public health concern.
      This preventable risk factor threatens both the mother and baby. Routine
      perinatal care visits offer opportunities for healthcare professionals to screen
      and refer abused women for effective interventions. It is, however, not clear
      which interventions best serve mothers during pregnancy and postpartum to ensure
      their safety. OBJECTIVES: To examine the effectiveness and safety of
      interventions in preventing or reducing domestic violence against pregnant women.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 July 2014), scanned bibliographies of published studies and
      corresponded with investigators. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) including cluster-randomised trials, and quasi
      randomised controlled trials (e.g. where there was alternate allocation)
      investigating the effect of interventions in preventing or reducing domestic
      violence during pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trials for inclusion and risk of bias, extracted data and
      checked them for accuracy. MAIN RESULTS: We included 10 trials with a total of
      3417 women randomised. Seven of these trials, recruiting 2629 women, contributed
      data to the review. However, results for all outcomes were based on single
      studies. There was limited evidence for the primary outcomes of reduction of
      episodes of violence (physical, sexual, and/or psychological) and prevention of
      violence during and up to one year after pregnancy (as defined by the authors of
      trials). In one study, women who received the intervention reported fewer
      episodes of partner violence during pregnancy and in the postpartum period (risk
      ratio (RR) 0.62, 95% confidence interval (CI) 0.43 to 0.88, 306 women, moderate
      quality). Groups did not differ for Conflict Tactics Score - the mean partner
      abuse scores in the first three months postpartum (mean difference (MD) 4.20
      higher, 95% CI -10.74 to 19.14, one study, 46 women, very low quality). The
      Current Abuse Score for partner abuse in the first three months was also similar
      between groups (MD -0.12 lower, 95% CI -0.31 lower to 0.07 higher, one study, 191
      women, very low quality). Evidence for the outcomes episodes of partner abuse
      during pregnancy or episodes during the first three months postpartum was not
      significant (respectively, RR 0.50, 95% CI 0.25 to 1.02, one study with 220
      women, very low quality; and RR 0.60, 95% CI 0.35 to 1.04, one study, 271 women,
      very low quality). Finally, the risk for low birthweight (< 2500 g) did not
      differ between groups (RR 0.74, 95 % CI 0.41 to 1.32, 306 infants, low
      quality).There were few statistically significant differences between
      intervention and control groups for depression during pregnancy and the postnatal
      period. Only one study reported findings for neonatal outcomes such as preterm
      delivery and birthweight, and there were no clinically significant differences
      between groups. None of the studies reported results for other secondary
      outcomes: Apgar score less than seven at one minute and five minutes, stillbirth,
      neonatal death, miscarriage, maternal mortality, antepartum haemorrhage, and
      placental abruption. AUTHORS' CONCLUSIONS: There is insufficient evidence to
      assess the effectiveness of interventions for domestic violence on pregnancy
      outcomes. There is a need for high-quality, RCTs with adequate statistical power
      to determine whether intervention programs prevent or reduce domestic violence
      episodes during pregnancy, or have any effect on maternal and neonatal mortality
      and morbidity outcomes.

PMID- 25390770
TI  - Autofluorescence of choroidal melanomas.
AB  - PURPOSE: To report autofluorescence findings for two patients with choroidal
      melanomas. METHODS: Records and photographs for two patients with choroidal
      melanomas were reviewed. Fundus autofluorescence photography was performed using
      the Heidelberg confocal SLO system (Heidelberg Retina Angiograph; Heidelberg
      Engineering, Dossenheim, Germany). RESULTS: Both patients had lipofuscin over the
      melanoma. In Case 1, autofluorescence studies showed a linear streak of
      autofluorescence and patchy autofluorescence overlying the tumor. In Case 2,
      autofluorescence photographs showed the presence of small flecklike areas of
      autofluorescence over the melanoma. CONCLUSION: Fundus autofluorescence
      photography is an alternative method for imaging lipofuscin over choroidal
      lesions.

PMID- 25390768
TI  - CXCR2 and its related ligands play a novel role in supporting the pluripotency
      and proliferation of human pluripotent stem cells.
AB  - Basic fibroblast growth factor (bFGF) is a crucial factor sustaining human
      pluripotent stem cells (hPSCs). We designed this study to search the substitutive
      factors other than bFGF for the maintenance of hPSCs by using human placenta
      derived conditioned medium without exogenous bFGF (hPCCM-), containing chemokine
      (C-X-C motif) receptor 2 (CXCR2) ligands, including interleukin (IL)-8 and growth
      related oncogene alpha (GROalpha), which were developed on the basis of our
      previous studies. First, we confirmed that IL-8 and/or GROalpha play independent
      roles to preserve the phenotype of hPSCs. Then, we tried CXCR2 blockage of hPSCs
      in hPCCM- and verified the significant decrease of pluripotency-associated genes
      expression and the proliferation of hPSCs. Interestingly, CXCR2 suppression of
      hPSCs in mTeSRTM1 containing exogenous bFGF decreased the proliferation of hPSCs
      while maintaining pluripotency characteristics. Lastly, we found that hPSCs
      proliferated robustly for more than 35 passages in hPCCM- on a gelatin
      substratum. Higher CXCR2 expression of hPSCs cultured in hPCCM- than those in
      mTeSRTM1 was observable. Our findings suggest that CXCR2 and its related ligands
      might be novel factors comparable to bFGF supporting the characteristics of hPSCs
      and hPCCM- might be useful for the maintenance of hPSCs as well as for the
      accurate evaluation of CXCR2 role in hPSCs without the confounding influence of
      exogenous bFGF. 

PMID- 25390771
TI  - Fundus autofluorescence in retinopathy caused by deferoxamine toxicity.
AB  - PURPOSE: To describe the fundus autofluorescence photographic pattern in a case
      of deferoxamine retinopathy. METHODS: Observational case report. RESULTS: A 91
      year-old woman receiving intravenous deferoxamine treatment presented with a
      history of deteriorating vision in both eyes. Autofluorescence photography
      revealed well circumscribed areas of hyperautofluorescence that correlated with
      areas of pigmentation shown by color photography. Deferoxamine retinopathy was
      diagnosed. CONCLUSION: Fundus autofluorescence photography is a noninvasive
      imaging method for early detection of deferoxamine retinopathy and can be used to
      monitor the status of the macula in patients at risk for this toxicity.

PMID- 25390772
TI  - Autofluorescence imaging of acute syphilitic posterior placoid chorioretinitis.
AB  - PURPOSE: To evaluate the autofluorescence findings of acute syphilitic posterior
      placoid chorioretinitis (ASPPC). METHODS: Patients with ASPPC underwent complete
      ophthalmologic examinations, including biomicroscopy, fundus color photography,
      autofluorescence photography, and fluorescein angiography. RESULTS: As expected,
      the patients had a yellowish lesion in the posterior pole. However, the lesion
      appeared to have two components, a diffuse placoid yellow discoloration at the
      level of the retinal pigment epithelium (RPE) and focal yellow spots that
      appeared to lie on the RPE. The diffuse placoid yellow color change at the RPE
      level showed a slight generalized increase in autofluorescence admixed with tiny
      spots of decreased autofluorescence. The yellow collections in front of the RPE
      were intensely hyperautofluorescent. The placoid area showed fluorescein
      staining, while the yellow deposits blocked the background fluorescence.
      Treatment of syphilis caused resolution of the placoid changes with associated
      improvement in the autofluorescence and fluorescein abnormalities. CONCLUSION:
      Patients with ASPPC have autofluorescence abnormalities during the acute
      manifestations of the disorder that help in interpretation of the fluorescein
      angiographic findings. We found evidence that the RPE is primarily involved and
      there does not appear to be choriocapillaris occlusion in early lesions.

PMID- 25390773
TI  - Optical coherence tomography findings in hydroxychloroquine and chloroquine
      associated maculopathy.
AB  - BACKGROUND: Vision loss and maculopathy associated with hydroxychloroquine and
      chloroquine use are infrequent but significant adverse effects. Bull's eye
      maculopathy related to these drugs, including peripheral and macular pigment
      changes, has been described; however, to our knowledge, optical coherence
      tomography (OCT) findings of the associated retinal pigment epithelium (RPE)
      atrophy have not yet been reported. METHODS: Single case report. RESULTS: A 48
      year-old woman was treated with hydroxychloroquine (7.8 mg/[kg . d]) for 8 years
      followed by chloroquine (3.9 mg/[kg . d]) for 5 months for systemic lupus
      erythematosus. Fundus examinations for toxicity were conducted every 6 months.
      These medications were discontinued when the patient developed photopsias. Nine
      years after discontinuation, the patient further developed new scotomas and a
      bull's eye pattern RPE atrophy. The photographic and OCT findings of
      hydroxychloroquine- and chloroquine-associated maculopathy are presented along
      with guidelines on dosing and screening. CONCLUSION: The ophthalmologist's
      awareness of dosing guidelines and communication with prescribing physicians are
      important in preventing ocular toxicities associated with hydroxychloroquine and
      chloroquine. Current guidelines suggest the following maximal dosages:
      hydroxychloroquine, 6.5 mg/(kg . d); and chloroquine, 3 mg/(kg . d). A patient
      weighing <135 lb should not receive >400 mg of hydroxychloroquine daily.

PMID- 25390774
TI  - Optical coherence tomography in hydroxychloroquine retinopathy: two observational
      case reports.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) findings in two cases
      of hydroxychloroquine retinopathy. METHODS: Two patients with hydroxychloroquine
      retinopathy at the bull's eye stage were identified. Each patient underwent
      rigorous historical questioning to rule out known causes of macular atrophy and
      to determine contributing factors. Comprehensive ocular examination was
      performed, including dilated biomicroscopic examination of the macula and
      indirect ophthalmoscopic evaluation of the retinal periphery. Additional
      evaluation included fundus color photography with fluorescein angiography and
      OCT. RESULTS: Both patients had a medical history of arthritis treated by
      hydroxychloroquine (Nivaquine; total dose, 365 g). At the bull's eye stage, OCT
      confirms the presence of macular atrophy, as shown in our two cases. The retinal
      atrophy seems to be related to the whole thickness of the retinal layers.
      CONCLUSION: We report the OCT findings of two cases of macular atrophy associated
      with hydroxychloroquine retinopathy.

PMID- 25390775
TI  - Methylenetetrahydrofolate reductase gene mutation in a 16-year-old girl with
      combined central retinal vein occlusion/cilioretinal artery occlusion.
AB  - PURPOSE: This case report describes combined central retinal veincilioretinal
      artery occlusion in a 16-year-old healthy girl. To our knowledge, our patient is
      the youngest described so for in the MEDLINE literature. METHODS: The patient
      underwent a full history, physical examination, and extensive laboratory studies
      to determine the potential risk factors leading to her vascular occlusion.
      RESULTS: Her family history was significant for multiple miscarriages and early
      cerebrovascular events. Laboratory testing revealed a compound heterozygous
      mutation (C677T and A1298C) in the methylenetetrahydrofolate reductase (MTHFR)
      gene and an elevated factor VIII level. As a result of her ocular occlusive
      event, abnormal hypercoagulable findings, and family history, the hematologist
      treated her with folate and warfarin. She has had no further ocular or systemic
      thrombotic events to date. CONCLUSION: The combination of the compound
      heterozygous C677TA1298C MTHFR mutation and an elevated factor VIII level may
      lead to an increased thrombotic tendency and may have resulted in combined
      central retinal veincilioretinal artery occlusion in an otherwise healthy 16-year
      old girl.

PMID- 25390776
TI  - Progressive outer retinal necrosis complicated by combined central retinal vein
      and central retinal artery occlusions.
AB  - PURPOSE: To describe an uncommon presentation and course of progressive outer
      retinal necrosis. METHODS: A 36-year-old man presented with unilateral optic disk
      edema with enhancement of the optic nerve sheath shown by magnetic resonance
      imaging. Intravenous methylprednisolone treatment was initiated. RESULTS: Two
      days later, he developed multiple discrete areas of outer retinal opacification
      with areas of confluence in the periphery of the retina. Results of laboratory
      testing for antibody to human immunodeficiency virus were positive. Therapy for
      progressive outer retinal necrosis was initiated, and the patient developed
      combined central retinal vein and central retinal artery occlusions 3 days later.
      CONCLUSIONS: Although usually characterized by a lack of vascular inflammation,
      progressive outer retinal necrosis may lead to vascular occlusions.

PMID- 25390777
TI  - Sclerochoroidal calcification: idiopathic or associated with systemic disease?
AB  - BACKGROUND: Idiopathic sclerochoroidal calcification is a rare disorder that may
      be confused with a malignant tumor. In most patients, its etiology is unknown.
      Some patients have associated systemic disorders or syndromes. METHODS: We report
      the case history of a patient with hypercalcemia and extensive sclerochoroidal
      calcifications; furthermore, we evaluate a series of seven patients with
      sclerochoroidal calcification, investigating calcium-phosphorus metabolism and
      screening for primary renal tubular hypokalemic metabolic alkalosis syndromes.
      RESULTS: One patient was diagnosed with bilateral sclerochoroidal calcification;
      she had primary hyperparathyroidism due to a parathyroid adenoma. None of the
      other seven patients met the criteria of primary renal tubular hypokalemic
      metabolic alkalosis syndromes or had significant problems of calcium-phosphorus
      metabolism. Nevertheless, two of them had a history of kidney stones, whereas two
      others had a history of arthritis. CONCLUSION: For all patients with
      sclerochoroidal calcification, it is important to exclude primary renal tubular
      hypokalemic metabolic alkalosis syndromes such as Bartter and Gitelman syndromes,
      because these patients have a higher risk of cardiovascular morbidity especially
      during anesthesia.

PMID- 25390778
TI  - Idiopathic choroidal neovascularization in a patient with riehl's melanosis.
AB  - PURPOSE: To describe a case of idiopathic choroidal neovascularization (CNV) in a
      patient with Riehl melanosis. METHODS: Description of a 34-year-old woman with
      Riehl melanosis who developed CNV in the right eye. RESULTS: All other known
      causes of CNV were investigated and ruled out. CONCLUSION: Idiopathic CNV can
      develop in a patient with Riehl melanosis.

PMID- 25390779
TI  - Choroidal neovascular membrane secondary to primary hemochromatosis.
AB  - PURPOSE: To describe the findings for a patient with hemochromatosis, angioid
      streak-like changes, and choroidal neovascularization. METHODS: Case report.
      RESULTS: A 63-year-old man with primary hemochromatosis presented with recent
      vision loss. Visual acuity was 20/20 in the right eye and 20/70 in the left eye.
      Funduscopic examination and fluorescein angiography disclosed diffuse retinal
      pigment epithelial mottling, peripapillary hyperfluorescence, and a choroidal
      neovascular membrane lesion. CONCLUSION: Hemochromatosis may be associated with
      angioid streak-like changes in Bruch membrane, choroidal neovascularization, and
      diffuse retinal pigment epithelial changes.

PMID- 25390780
TI  - Bilateral circumscribed choroidal hemangioma in an otherwise healthy individual.
AB  - PURPOSE: To describe an extremely rare association of bilateral circumscribed
      hemangioma (CCH) in the absence of any other evidence of systemic abnormalities.
      METHODS: A 43-year-old man was referred to our institution with a diagnosis of
      probable unilateral hemangioma of the right eye with decreased visual acuity.
      RESULTS: Funduscopic examination of both eyes revealed one CCH in each eye.
      Fluorescein angiography, indocyanine green angiography, and A- and B-scan
      ultrasonography confirmed the diagnosis. General examination, endocrinological
      testing, and imagery workup did not show any abnormality. The right eye was
      treated with low-dose external-beam irradiation with complete recovery of visual
      acuity. CONCLUSION: Bilateral choroidal localization of tumoral lesions raises
      the question about their primary or metastatic onset. To our knowledge, bilateral
      CCH has been reported only in association with Sturge-Weber or Klippel-Trenaunay
      Weber syndrome. The bilateral CCH localization in a healthy individual represents
      an extremely uncommon condition, which may represent a low penetrance phenotype
      of Sturge-Weber syndrome.

PMID- 25390781
TI  - Macular hole surgery in alport syndrome.
AB  - BACKGROUND: Alport syndrome, an X-linked disease, includes progressive hematuric
      nephritis leading to renal failure, hearing loss, and ocular changes including
      macular holes. Females have a more variable systemic and ophthalmic course
      compared to males. Macular holes have been described mostly in males, but not
      with therapeutic attempts. METHODS: A case report of a woman with large bilateral
      macular holes who underwent anatomically successful macular hole surgery in one
      eye. RESULTS: A 30-year-old woman with a 9-year history of decreased vision,
      probably due to bilateral macular holes, complained of progressive visual loss.
      Visual acuity was 20/400 in the right eye and 20/800 in the left. Optical
      coherence tomography showed large macular holes, measuring 1350 MUm in the right
      eye and 2050 MUm in the left. Visual acuity improved to 20/80 after macular hole
      surgery in the right eye using standard techniques. CONCLUSION: Abnormal collagen
      synthesis may account for many findings in Alport syndrome. Its role in macular
      hole pathogenesis may be to accelerate passage of fluid through a structurally
      abnormal Bruch membrane yielding microcystic cavities which may coalesce and
      rupture, or due to potentiated vitreoretinal traction at the vitreoretinal
      interface. Macular hole surgery may benefit selected patients.

PMID- 25390782
TI  - Surgical removal of the internal limiting membrane in progressive macular change
      in x-linked juvenile retinoschisis.
AB  - PURPOSE: To report two cases of progressive macular changes in X-linked juvenile
      retinoschisis (XLRS) treated with vitrectomy. PATIENTS: A 16-year-old boy and a
      13-year-old boy with progressive deterioration of vision underwent vitrectomy
      with internal limiting membrane peeling with or without gas injection for
      vitreous traction. Optical coherence tomography was performed to monitor
      morphologic changes of the macula before and after surgery. RESULTS: During
      follow-up (at 6 months and 3 months, respectively), both patients had anatomical
      improvement and minimal improvement in vision. CONCLUSION: We postulate that
      vitreous tractional force causes the progressive structural deformity of the
      macula in XLRS.

PMID- 25390783
TI  - Regression of macular drusen after pars plana vitrectomy in a patient with age
      related macular degeneration.
AB  - PURPOSE: To report a case of marked regression of drusen and a pigment epithelial
      detachment (PED) with visual improvements after pars plana vitrectomy (PPV).
      METHODS: A 67-year-old man noticed gradual visual deterioration to 20/80 due to
      macular soft drusen and a PED. A posterior vitreous detachment (PVD) was not
      present in the affected eye. RESULTS: PPV was performed to create a PVD, and
      there was marked regression of drusen and a PED with visual improvement to 20/30.
      Vision was maintained at the final examination 30 months after surgery.
      CONCLUSION: Vitrectomy may be considered for treatment of macular drusen and
      prevention of choroidal neovascularization.

PMID- 25390784
TI  - Peripheral retinal neovascularization and retinal detachment in turner syndrome.
AB  - BACKGROUND: Peripheral retinal neovascularization occurs in many diseases,
      including sickle-cell disease, Eales disease, and sarcoidosis. To our knowledge,
      combined retinal detachment with peripheral retinal neovascularization has not
      been reported in the literature. METHODS: We examined a 14-year-old girl with
      Turner syndrome. Total rhegmatogenous retinal detachment and tractional retinal
      detachment were found in the left eye, and peripheral avascular zone with
      neovascularization was found in both eyes. The retinal detachment was treated
      with an encircling scleral buckle. Subsequent retinal photocoagulation over the
      avascular zones of both eyes was performed. RESULTS: Retinal neovascularizations
      regressed, and the retinal detachment reattached after treatment. CONCLUSIONS:
      Retinal neovascularization, rhegmatogenous retinal detachment, and tractional
      retinal detachment can be ocular findings associated with Turner syndrome.
      Retinal photocoagulation over the avascular zone is a possible treatment for
      neovascularization.

PMID- 25390785
TI  - Primary central nervous system lymphoma with intraocular recurrence after optic
      nerve disorder.
AB  - PURPOSE: To describe a patient with primary central nervous system lymphoma
      (PCNSL) who developed intraocular recurrence after the onset of optic nerve
      disorder. METHODS: A 46-year-old woman developed bilateral central vision loss 1
      year after the onset of PCNSL. Ophthalmologic examination, including perimetry,
      magnetic resonance imaging, and determination of visual evoked potential, was
      performed. RESULTS: These examinations revealed a diagnosis of bilateral optic
      nerve disorder, and optic nerve disorder spontaneously resolved. Six months
      later, the patient had blurred vision in the left eye. Funduscopic examination
      revealed dense vitreous opacity and geographic subretinal exudates. Cytologic
      analysis of vitreous obtained by pars plana vitrectomy led to a diagnosis of
      recurrent intraocular lymphoma. The patient again developed brain recurrence 8
      months after chemotherapy for intraocular recurrence. CONCLUSION: The clinical
      course in this case suggests that lymphoma cells infiltrated from the brain into
      the eye along the optic nerve.

PMID- 25390786
TI  - Optical coherence tomography findings in welder's maculopathy.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) findings in two
      patients with welder's maculopathy. METHODS: Retrospective cases series. In
      addition to examination by slit lamp biomicroscopy, color fundus photographs and
      OCT images were obtained from patients with welder's maculopathy. RESULTS: Both
      patients had a history of bilateral decreased central vision after welding
      without appropriate eye protection. Yellowish foveal spots developed in the acute
      stage, evolving over several months into well demarcated lamellar foveal defects
      with surrounding retinal pigment epithelium changes. OCT showed interruption of
      the inner high reflective layer (HRL) corresponding to the level of the outer
      neurosensory retina. These appearances are similar to those seen in solar
      maculopathy. CONCLUSIONS: OCT shows disruption of the inner HRL in late welder's
      maculopathy. These appearances are similar to those seen in late solar
      maculopathy. OCT can be a useful tool in confirming the diagnosis and
      understanding the pathogenesis of photic maculopathy.

PMID- 25390787
TI  - Senior-loken syndrome complicated with severe coats disease-like exudative
      retinopathy.
AB  - BACKGROUND: Senior-Loken syndrome is a rare disorder that combines juvenile
      nephronophthisis with retinitis pigmentosa. METHODS: Case report. RESULTS: A 9
      year-old Japanese girl diagnosed with Senior-Loken syndrome subsequently
      developed severe Coats disease-like exudative retinopathy. Although retinal
      coagulation, pars plana lensectomy, and vitrectomy were performed, she lost light
      perception in both eyes. CONCLUSION: Faulty vascular morphogenesis and its
      dysfunction might contribute to the development of Coats disease-like exudative
      retinopathy in Senior-Loken syndrome.

PMID- 25390788
TI  - Treatment of bilateral candidal endophthalmitis with intravenous caspofungin.
AB  - PURPOSE: Fungal resistances to drugs are increasing. Caspofungin is a new
      antifungal agent effective in the treatment of invasive candidiasis. We report a
      case of candidal endophthalmitis that responded adequately to caspofungin.
      METHODS: A 24-year-old man with acute myeloid leukemia presented with vision loss
      in both eyes. Visual acuity was 20/50 in the right eye and counting fingers in
      the left eye. Fundus examination revealed multiple, premacular, vitreous, pearl
      stringshaped condensations in the right eye and a subretinal abscess in the left
      eye. Treatment with 50 mg of intravenous caspofungin once daily was started.
      RESULTS: After 1 month, inflammation in both eyes had decreased, although the
      left eye developed macular scarring. Medication at discharge was intravenous
      caspofungin once daily for another 6 weeks. Nine months after presentation, the
      patient had residual vitreous condensations in the premacular region of the right
      eye with visual acuity of 20/25 and severe macular scarring in the left eye with
      visual acuity of 20/100. CONCLUSION: This case adds support for the use of
      caspofungin as monotherapy for candidal endophthalmitis. Further studies are
      necessary to determine treatment options for the new antifungal agents.

PMID- 25390789
TI  - Retinal laser injury during a laser show.
AB  - BACKGROUND: Laser injuries caused by Q-switched lasers are not unusual in the
      military and laboratories. To our knowledge, only one case of eye injury during a
      laser show has been reported previously. METHODS: Case series. RESULTS: All three
      patients had uniocular foveal hemorrhagic injury demonstrated by fluorescein
      angiography and optical coherence tomography. The lesions resolved within 6
      months. CONCLUSIONS: Laser retinal injuries can cause transient or permanent
      visual damage. Accidental eye injuries during a laser show may be possible.

PMID- 25390790
TI  - De novo mutation in a choroideremia carrier.
AB  - PURPOSE: To describe a de novo gene mutation in a female patient with clinically
      characteristic findings of choroideremia (CHM). METHODS: Determination of best
      corrected visual acuity, fundus examination, visual field analysis, and
      electroretinography were performed on a female patient with an advanced CHM
      phenotype. Blood samples were obtained from the patient and both her parents, and
      direct genomic sequencing for DNA analysis was performed on the blood samples.
      RESULTS: A single base-pair sequence change was identified in codon 293 in exon 7
      (R293X) of the CHM gene in the proband. This mutation was not found to occur in
      her clinically unaffected parents. CONCLUSION: These findings document that a de
      novo point mutation should be considered when an isolated female family member is
      found to have CHM.

PMID- 25390791
TI  - Endophthalmitis after 25-gauge pars plana vitrectomy.
AB  - BACKGROUND: Twenty-five-gauge vitrectomy is a sutureless procedure that allows
      surgery performed thorough transconjunctival incisions, but the possibility of
      intraocular infection exists. METHODS: We report a case of endophthalmitis after
      minimally invasive vitrectomy and discuss the possible mechanisms of this
      complication. RESULTS: Twenty-five-gauge vitrectomy was performed to treat a
      patient with proliferative diabetic retinopathy. On the third postoperative day,
      infectious endophthalmitis was diagnosed, and the patient immediately underwent
      surgery. After conjunctival dissection, "mushroom-shaped" tissue and purulent
      discharge were observed at the sclerotomy sites. On the third day after
      reoperation, visual acuity was no light perception, and the patient underwent
      evisceration. CONCLUSION: We believe that vitreous incarceration after 25-gauge
      vitrectomy is an additional risk factor for intraocular infection. It is
      important to exclude vitreous incarceration after removal of the trocar in
      addition to conjunctival displacement prior to trocar insertion and beveled
      incision. Instillation of trypan blue stains the extruded vitreous, pointing out
      the tissue to be removed at the end of the procedure and minimizing the
      possibility of intraocular infection. Other risk factors include
      immunossupresion, long duration of the procedure, and multiple instrument entry
      through the sclerotomy.

PMID- 25390792
TI  - Ultrasound-guided transoral drainage of a paediatric parapharyngeal abscess.
AB  - OBJECTIVE: To report and discuss the surgical use of ultrasonography for draining
      a parapharyngeal space infection in a child. CASE REPORT: The use of image-guided
      surgery for draining a parapharyngeal abscess has been previously reported, with
      computed tomography for an intra-oral approach and ultrasound for an external
      approach. We present the first case report of a four-year-old child with a
      retropharyngeal abscess and a deep parapharyngeal abscess in whom neck ultrasound
      was used to assist intra-oral drainage. CONCLUSION: Neck ultrasound may be used
      in paediatric patients to visualise access to the parapharyngeal space through
      the intra-oral route for abscess drainage.

PMID- 25390794
TI  - Knowledge, attitudes and practices regarding cervical cancer and screening among
      Haitian health care workers.
AB  - It is estimated that Haiti has the highest incidence of cervical cancer in the
      Western Hemisphere. There are currently no sustainable and affordable cervical
      cancer screening programs in Haiti. The current status of screening services and
      knowledge of health care professionals was assessed through a Knowledge,
      Attitudes, and Practices survey on cervical cancer screening and prevention. It
      was distributed to Project Medishare for Haiti health care workers (n = 27) in
      the Central Plateau. The majority (22/27) of participants stated pre-cancerous
      cells could be detected through screening, however, only four had ever performed
      a pap smear. All of the participants felt a screening program should be started
      in their area. Our data establishes that knowledge is fairly lacking among
      healthcare workers and there is an opportunity to train them in simple, cost
      effective "screen-and-treat" programs that could have a great impact on the
      overall health of the population.

PMID- 25390793
TI  - Predicting suicides after psychiatric hospitalization in US Army soldiers: the
      Army Study To Assess Risk and rEsilience in Servicemembers (Army STARRS).
AB  - IMPORTANCE: The US Army experienced a sharp increase in soldier suicides
      beginning in 2004. Administrative data reveal that among those at highest risk
      are soldiers in the 12 months after inpatient treatment of a psychiatric
      disorder. OBJECTIVE: To develop an actuarial risk algorithm predicting suicide in
      the 12 months after US Army soldier inpatient treatment of a psychiatric disorder
      to target expanded posthospitalization care. DESIGN, SETTING, AND PARTICIPANTS:
      There were 53,769 hospitalizations of active duty soldiers from January 1, 2004,
      through December 31, 2009, with International Classification of Diseases, Ninth
      Revision, Clinical Modification psychiatric admission diagnoses. Administrative
      data available before hospital discharge abstracted from a wide range of data
      systems (sociodemographic, US Army career, criminal justice, and medical or
      pharmacy) were used to predict suicides in the subsequent 12 months using machine
      learning methods (regression trees and penalized regressions) designed to
      evaluate cross-validated linear, nonlinear, and interactive predictive
      associations. MAIN OUTCOMES AND MEASURES: Suicides of soldiers hospitalized with
      psychiatric disorders in the 12 months after hospital discharge. RESULTS: Sixty
      eight soldiers died by suicide within 12 months of hospital discharge (12.0% of
      all US Army suicides), equivalent to 263.9 suicides per 100,000 person-years
      compared with 18.5 suicides per 100,000 person-years in the total US Army. The
      strongest predictors included sociodemographics (male sex [odds ratio (OR), 7.9;
      95% CI, 1.9-32.6] and late age of enlistment [OR, 1.9; 95% CI, 1.0-3.5]),
      criminal offenses (verbal violence [OR, 2.2; 95% CI, 1.2-4.0] and weapons
      possession [OR, 5.6; 95% CI, 1.7-18.3]), prior suicidality [OR, 2.9; 95% CI, 1.7
      4.9], aspects of prior psychiatric inpatient and outpatient treatment (eg, number
      of antidepressant prescriptions filled in the past 12 months [OR, 1.3; 95% CI,
      1.1-1.7]), and disorders diagnosed during the focal hospitalizations (eg,
      nonaffective psychosis [OR, 2.9; 95% CI, 1.2-7.0]). A total of 52.9% of
      posthospitalization suicides occurred after the 5% of hospitalizations with
      highest predicted suicide risk (3824.1 suicides per 100,000 person-years). These
      highest-risk hospitalizations also accounted for significantly elevated
      proportions of several other adverse posthospitalization outcomes (unintentional
      injury deaths, suicide attempts, and subsequent hospitalizations). CONCLUSIONS
      AND RELEVANCE: The high concentration of risk of suicide and other adverse
      outcomes might justify targeting expanded posthospitalization interventions to
      soldiers classified as having highest posthospitalization suicide risk, although
      final determination requires careful consideration of intervention costs,
      comparative effectiveness, and possible adverse effects.

PMID- 25390795
TI  - 2014 Future Earth Young Scientists Conference on integrated science and knowledge
      co-production for ecosystems and human well-being.
AB  - Effective integration in science and knowledge co-production is a challenge that
      crosses research boundaries, climate regions, languages and cultures. Early
      career scientists are crucial in the identification of, and engagement with,
      obstacles and opportunities in the development of innovative solutions to complex
      and interconnected problems. On 25-31 May 2014, International Council for Science
      and International Social Science Council, in collaboration with the International
      Network of Next-Generation Ecologists and Institute for New Economic Thinking:
      Young Scholars Initiative, assembled a group of early career researchers with
      diverse backgrounds and research perspectives to reflect on and debate relevant
      issues around ecosystems and human wellbeing in the transition towards green
      economy, funded by the German Research Foundation, at Villa Vigoni, Italy. As a
      group of young scientists, we have come to a consensus that collaboration and
      communication among a diverse group of peers from different geographic regions
      could break down the barriers to multi-disciplinary research designed to solve
      complex global-scale problems. We also propose to establish a global systematic
      thinking to monitor global socio-ecological systems and to develop criteria for a
      "good" anthropocene. Finally, we aim to bridge gaps among research, the media,
      and education from a governance perspective linking with "sustainable development
      goals".

PMID- 25390796
TI  - AgNP-DNA@GQDs hybrid: new approach for sensitive detection of H2O2 and glucose
      via simultaneous AgNP etching and DNA cleavage.
AB  - A growing body of evidence suggests that hydrogen peroxide (H2O2) plays an active
      role in the regulation of various physiological processes. Development of
      sensitive probes for H2O2 is an urgent work. In this study, we proposed a DNA
      mediated silver nanoparticle and graphene quantum dot hybrid nanocomposite (AgNP
      DNA@GQDs) for sensitive fluorescent detection of H2O2. The sensing mechanism is
      based on the etching effect of H2O2 to AgNPs and the cleavage of DNA by as
      generated hydroxyl radicals (*OH). The formation of AgNP-DNA@GQDs nanocomposite
      can result in fluorescence quenching of GQDs by AgNPs through the resonance
      energy transfer. Upon H2O2 addition, the energy transfer between AgNPs and GQDs
      mediated by DNA was weakened and obvious fluorescence recovery of GQDs could be
      observed. It is worth noting that the reaction product *OH between H2O2 and AgNPs
      could cleave the DNA-bridge and result in the disassembly of AgNP-DNA@GQDs to
      achieve further signal enhancement. With optimal conditions, the approach
      achieves a low detection limit of 0.10 MUM for H2O2. Moreover, this nanocomposite
      is further extended to the glucose sensing in human urine combining with glucose
      oxidase (GOx) for the oxidation of glucose and formation of H2O2. The glucose
      concentrations in human urine are detected with satisfactory recoveries of 94.6
      98.8% which holds potential for ultrasensitive quantitative analysis of glucose
      and supplies valuable information for diabetes mellitus research and clinical
      diagnosis. 

PMID- 25390797
TI  - Solution synthesis of metal silicide nanoparticles.
AB  - Transition-metal silicides are part of an important family of intermetallic
      compounds, but the high-temperature reactions that are generally required to
      synthesize them preclude the formation of colloidal nanoparticles. Here, we show
      that palladium, copper, and nickel nanoparticles react with monophenylsilane in
      trioctylamine and squalane at 375  degrees C to form colloidal Pd(2)Si, Cu(3)Si,
      and Ni(2)Si nanoparticles, respectively. These metal silicide nanoparticles were
      screened as electrocatalysts for the hydrogen evolution reaction, and Pd(2)Si and
      Ni(2)Si were identified as active catalysts that require overpotentials of -192
      and -243 mV, respectively, to produce cathodic current densities of -10 mA cm(
      2).

PMID- 25390798
TI  - Gold(I)-catalyzed polycyclization of linear dienediynes to seven-membered ring
      containing polycycles via tandem cyclopropanation/Cope rearrangement/C-H
      activation.
AB  - A novel gold(I)-catalyzed polycyclization of easily prepared linear dienediynes
      has been developed for the construction of fused 5,7,6-tricyclic ring systems in
      one step with high diastereocontrol. The polycyclization, a formal [4 + 3]/C-H
      activation reaction, takes place through gold(I)-catalyzed intramolecular
      cyclopropanation of diene with diyne, Cope rearrangement of cis
      alkenylalkynylcyclopropane, aliphatic C-H activation via a seven-membered-ring
      allene intermediate, and [1,2]-H and -G (H or OAc) shifts. 

PMID- 25390799
TI  - The gut microbiota and its correlations with the central nervous system
      disorders.
AB  - A mutual impact of gastrointestinal tract (GIT) and central nervous system (CNS)
      functions has been recognized since the mid-twentieth century. It is accepted
      that the so-called gut-brain axis provides a two-way homeostatic communication,
      through immunological, hormonal and neuronal signals. A dysfunction of this axis
      has been associated with the pathogenesis of some diseases both within and
      outside the GIT, that have shown an increase in incidence over the last decades.
      Studies comparing germ-free animals and animals exposed to pathogenic bacterial
      infections, probiotics or antibiotics suggest the participation of the microbiota
      in this communication and a role in host defense, regulation of immunity and
      autoimmune disease appearance. The GIT could represent a vulnerable area through
      which pathogens influence all aspects of physiology and even induce CNS neuro
      inflammation. All those concepts may suggest the modulation of the gut microbiota
      as an achievable strategy for innovative therapies in complex disorders. Moving
      from this background, the present review discusses the relationship between
      intestinal microbiota and CNS and the effects in health and disease. We
      particularly look at how the commensal gut microbiota influences systemic immune
      response in some neurological disorders, highlighting its impact on pain and
      cognition in multiple sclerosis, Guillain-Barre Syndrome, neurodevelopmental and
      behavioral disorders and Alzheimer's disease. In this review we discuss recent
      studies showing that the potential microbiota-gut-brain dialogue is implicated in
      neurodegenerative diseases. Gaining a better understanding of the relationship
      between microbiota and CNS could provide an insight on the pathogenesis and
      therapeutic strategies of these disorders. 

PMID- 25390800
TI  - Surgical technique for removal of a capsular tension ring from the vitreous
      cavity.
AB  - PURPOSE: To describe a surgical technique for removing a posteriorly dislocated
      capsular tension ring (CTR). METHODS: Retrospective interventional case report.
      CASE REPORT: A 68-year-old African American man underwent cataract surgery. Early
      in the procedure, a CTR was placed at the equator of the lens capsule.
      Subsequently, the posterior capsule ruptured. The CTR was left in place, and an
      intraocular lens was placed in the sulcus. On postoperative Day 6, the CTR
      subluxated into the vitreous cavity and was removed without complication by pars
      plana vitrectomy, using the CTR inserter. CONCLUSION: The technique of using the
      CTR inserter to remove the CTR from the vitreous cavity appears to be safe and
      effective.

PMID- 25390801
TI  - Acute exudative polymorphous vitelliform maculopathy in a young woman:
      presymptomatic findings and 21-month follow-up.
AB  - PURPOSE: To describe ocular findings before and after the diagnosis of acute
      exudative polymorphous vitelliform maculopathy, in an otherwise healthy 28-year
      old woman. METHODS: Case report with 21-months of follow-up. Fundus photography,
      optical coherence tomography, fluorescein angiography, indocyanine green
      angiography, and autofluorescence were used for imaging the retina. To examine
      retinal function, full-field electroretinogram, multifocal electroretinogram,
      electrooculography, and dark adaptometry were performed. Genetic analysis for
      mutations associated with Best disease was done. RESULTS: In the asymptomatic
      patient before diagnosis, white-yellow, drusen-like, subretinal depositions were
      found in both eyes. A few months later, the patient developed bilateral visual
      disturbances. Retinal examination at the acute phase revealed a characteristic
      pattern of multifocal white-yellow subretinal lesions in both posterior poles,
      imaged by ophthalmoscopy, fluorescein angiography, indocyanine green angiography,
      and optical coherence tomography. Additionally, electrooculography and dark
      adaptometry were abnormal. Full-field electroretinogram was normal, but
      multifocal electroretinogram revealed central depression of peak amplitudes.
      During the 21-month follow-up without any treatment, visual acuity recovered,
      electrooculography and dark adaptometry normalized, and the patient experienced
      one episode of relapse. Genetic studies excluded mutations in the bestrophin gene
      (BEST1). CONCLUSION: Acute exudative polymorphous vitelliform maculopathy is
      still a condition of unknown origin, primarily affecting the pigment epithelium.
      Earlier reports have discussed whether the condition is inherited or acquired. In
      this report, the presymptomatic retinal findings in acute exudative polymorphous
      vitelliform maculopathy are described for the first time, indicating that a
      condition may be associated with primarily affected retinal pigment epithelium.

PMID- 25390802
TI  - Spectral domain optical coherence tomography findings in tamoxifen retinopathy--a
      case report.
AB  - PURPOSE: To report spectral domain optical coherence tomography findings in a
      case of typical tamoxifen retinopathy. METHODS: In this observational case
      report, a patient with tamoxifen retinopathy was imaged with spectral domain
      optical coherence tomography and fundus auto fluorescence. RESULTS: Spectral
      domain optical coherence tomography showed numerous hyperreflective spots within
      the retina, mainly in the inner retinal layers in both the eyes. The external
      limiting membrane, the Inner Segment-Outer Segment junction, and the
      photoreceptors were not discernable at the fovea in the right eye. In the left
      eye, there was foveal atrophy with total loss of photoreceptors. The
      autofluorescent images showed macular hypofluorescence with foveal
      hyperfluorescence. CONCLUSION: Spectral domain optical coherence tomography
      demonstrated abnormalities in the outer retinal layers in tamoxifen retinopathy.
      There were also characteristic alterations in the autofluorescence pattern at the
      macula in tamoxifen retinopathy.

PMID- 25390803
TI  - Human herpes virus-6 as a cause of recurrent posterior uveitis in a HIV-positive
      patient.
AB  - PURPOSE: To report a case of bilateral recurrent posterior uveitis caused by
      human herpes virus-6 (HHV-6) in a human immunodeficiency virus-positive
      individual. METHODS: Comprehensive ophthalmic examination, including imaging with
      optical coherence tomography, fluorescein and indocyanine green angiography, and
      adequate laboratory tests were performed. A human immunodeficiency virus-positive
      patient without any AIDS defining condition, with a history of recurrent
      bilateral posterior uveitis referred to us with the diagnosis of retinal
      detachment. RESULTS: Vitreous polymerase chain reaction detected an aberrant band
      for herpes viruses, which proved to be human herpes virus-6 by repeated
      polymerase chain reactions. Serum antibodies titer was positive for human herpes
      virus-6. The patient responded well to antiviral therapy with valacyclovir.
      CONCLUSION: This is the first case of human herpes virus-6-related bilateral
      posterior uveitis in a human immunodeficiency virus-positive individual without
      clinical manifestations of AIDS.

PMID- 25390804
TI  - Topical steroidal and nonsteroidal antiinflammatory drugs for the treatment of
      cystoid macular edema in retinitis pigmentosa.
AB  - PURPOSE: Oral carbonic anhydrase inhibitors have been the treatment of choice for
      managing cystoid macular edema (CMO) in retinitis pigmentosa. We report a case
      illustrating the effectiveness of topical steroidal and nonsteroidal
      antiinflammatory drugs (NSAIDs) in managing CMO in a patient with retinitis
      pigmentosa, who is unable to take oral carbonic anhydrase inhibitor because of
      chronic renal impairment. METHODS: An 85-year-old woman with retinitis pigmentosa
      related CMO in the left eye was prospectively followed up after treatment with a
      4 times daily regimen consisting of a topical steroid (prednisolone acetate 1%)
      and an NSAID (ketorolac trometamol 0.5%). The right eye showed no evidence of
      CMO. Oral acetazolamide was avoided as the patient had chronic renal impairment.
      RESULTS: Three months after treatment, best-corrected visual acuity in the left
      eye improved from 20/200 to 20/60, and spectral domain optical coherence
      tomography showed complete resolution of CMO. Topical steroid and NSAID were
      therefore stopped. However, 6 months later, left best-corrected visual acuity was
      reduced to 20/120 and spectral domain optical coherence tomography showed
      recurrence of CMO. This was managed with the same treatment regimen of topical
      steroid and NSAID, which resulted in complete resolution of CMO with best
      corrected visual acuity in the left eye improving to 20/80 after 3 months.
      CONCLUSION: To our knowledge, this is the first report that demonstrates the
      effectiveness of topical steroids or NSAIDs in managing CMO in a retinitis
      pigmentosa patient with chronic renal impairment who is unable to take a carbonic
      anhydrase inhibitor because of chronic renal impairment.

PMID- 25390805
TI  - Bilateral diffuse uveal melanocytic proliferation associated with renal cell
      carcinoma.
AB  - PURPOSE: To report a case of bilateral diffuse uveal melanocytic proliferation
      associated with an asymptomatic renal cell carcinoma. DESIGN: Clinical case
      report. METHODS: A 70-year-old man presented with a 7-month history of bilateral
      visual loss. Ophthalmoscopic examination, fluorescein angiography, ocular
      coherence tomography, and a search for underlying systemic malignancy were
      performed. RESULTS: Examination revealed multiple melanocytic uveal
      proliferations in both eyes. Fluorescein angiography revealed a pattern of
      multiple areas of early hyperfluorescence, and ocular coherence tomography showed
      serous detachment of the central retina. Abdominal computerized tomography scans
      showed a large tumor in the left kidney and nodular involvement in the right
      kidney. Pathologic examination revealed a clear cell carcinoma of the kidney.
      CONCLUSION: A literature review revealed a total of 40 cases of bilateral diffuse
      uveal melanocytic proliferation. To our knowledge, this is the first case to be
      associated with renal cell carcinoma.

PMID- 25390806
TI  - Early spontaneous closure after reopening of a previously repaired macular hole.
AB  - PURPOSE: To describe a case of early spontaneous closure of macular hole after
      reopening after previous successful surgical repair. METHODS: A 72-year-old
      female patient was treated for stage 2 idiopathic macular hole in the right eye.
      The hole remained anatomically closed for 2 months postoperatively, before
      reopening 1 month later. RESULTS: The patient was listed for revision surgery;
      however, on the day of the operation, which was 2 months after the reopening, the
      hole seemed to have closed spontaneously. Two years later, the macular hole
      remains closed with best-corrected visual acuity of 6/9. CONCLUSION: Spontaneous
      closure of macular holes after reopening is a rare phenomenon. The case presented
      here demonstrates that for early reopening of macular holes, a period of
      observation with serial optical coherence tomography may allow the hole to close
      spontaneously before proceeding with further surgical intervention.

PMID- 25390807
TI  - The dexamethasone suppression test for the diagnosis of Cushing syndrome in a
      patient with central serous chorioretinopathy.
AB  - PURPOSE: To describe a case whereby the dexamethasone suppression test was used
      to diagnose Cushing syndrome in a patient presenting with central serous
      chorioretinopathy. METHODS: A 60-year-old woman presented with central serous
      chorioretinopathy and was investigated with the dexamethasone suppression test;
      the result was positive and lead to a diagnosis of an adrenal tumor. RESULTS: The
      adrenal tumor was removed and her central serous chorioretinopathy resolved.
      CONCLUSION: The dexamethasone suppression test can be used safely in an
      outpatient procedure to investigate cases of central serous chorioretinopathy,
      and it may be a useful screening tool in these patients.

PMID- 25390808
TI  - Acute macular neuroretinopathy associated with the use of norepinephrine reuptake
      inhibitors: a case series and OCT findings.
AB  - PURPOSE: The purpose of this study was to report a case series of patients with
      acute macular neuroretinopathy in which patients concomitantly used oral
      norepinephrine reuptake inhibitors. METHODS: Retrospective case review. PATIENTS:
      Three patients with retinal findings consistent with acute macular
      neuroretinopathy are presented. CONCLUSION: The use of oral neuromodulators
      should be considered in cases of acute macular neuroretinopathy.

PMID- 25390809
TI  - Microbubble in the hole: a rare cause of failed macular hole surgery?
AB  - PURPOSE: To present a failed macular hole surgery with gas microbubble retention
      within the hole. METHODS: A 68-year-old female patient with a Stage 2 macular
      hole underwent vitrectomy with removal of posterior hyaloid and 12% C3F8 gas
      injection. Because the macular hole was Stage 2 and posterior hyaloid was
      observed to be firmly attached over the macular area, no attempt was made for
      peeling of internal limiting membrane. Postoperatively, the patient was
      instructed to keep a facedown posture for 1 week. At 1-month visit,
      ophthalmoscopy revealed a tiny gas bubble filling the macular hole that failed to
      close. RESULTS: The patient underwent a repeat vitrectomy in which internal
      limiting membrane was peeled, and the eye was filled with 20% SF6. At 2-week
      follow-up visit, the hole was observed to be closed. CONCLUSION: The reason for
      the macular hole nonclosure in this case may be the lack of internal limiting
      membrane peeling in the first operation. However, the authors believe that
      microbubble localized within the hole might have contributed to the failure.

PMID- 25390810
TI  - Acute unilateral toxoplasma retinochoroiditis associated with adalimumab, a tumor
      necrosis factor-alpha antagonist.
AB  - PURPOSE: The purpose of this study was to report a case of a patient with
      unilateral toxoplasma retinochoroiditis while on treatment with adalimumab, an
      anti-tumor necrosis factor alpha agent for ulcerative colitis. METHODS: This is a
      descriptive case report. RESULTS AND DISCUSSION: In addition to the patient with
      toxoplasma retinochoroiditis, there is one published report of two patients who
      developed toxoplasma chorioretinitis while on anti-tumor necrosis factor alpha
      therapy for rheumatoid arthritis: one was on adalimumab and methotrexate and the
      other one was on etanercept and methotrexate. CONCLUSION: The authors need to be
      aware of this potentially vision threatening risk with anti-tumor necrosis factor
      alpha therapy.

PMID- 25390811
TI  - Multifocal choroiditis with panuveitis in a patient with disseminated
      Mycobacterium avium complex.
AB  - PURPOSE: The authors present a case of multifocal choroiditis and panuveitis
      secondary to disseminated Mycobacterium avium complex infection in a patient with
      human immunodeficiency virus/AIDS. METHOD: Case report and review of relevant
      literature. RESULTS: A 48-year-old woman with human immunodeficiency virus was
      admitted for the work up of abdominal pain, fevers, and weight loss. She was
      noncompliant with antiretroviral therapy with a CD4 count of 30 * 10/L. She
      reported bilateral reduction in vision with corrected acuities of 6/18 in the
      right eye and 6/36 in the left eye. Bilateral granulomatous panuveitis with
      multifocal choroiditis was present. A vitreous biopsy of the left eye confirmed
      Mycobacterium avium complex, also identified on mycobacterium blood cultures. She
      was started on oral azithromycin and ethambutol, and after 6 months, her
      corrected acuities were 6/9 in the right eye bilaterally with an improvement in
      uveitis and choroiditis. CONCLUSION: Mycobacterium avium complex infection should
      be considered as a cause of visual impairment in patients with human
      immunodeficiency virus/AIDS. Early detection and prompt management are essential
      for the prevention of visual and other systemic complications.

PMID- 25390812
TI  - An unusual case of high altitude-like retinopathy caused by anemia and
      thrombocytopenia at recreational altitude.
AB  - PURPOSE: To report an unusual presentation of high altitude-like retinopathy at
      recreational altitude after chemotherapy-induced anemia and thrombocytopenia.
      METHODS: Case report. RESULTS: A 43-year-old man undergoing chemotherapy for
      testicular cancer traveled to an altitude of 2,930 m and subsequently developed
      significant visual deficit in his right eye and was later diagnosed with
      bilateral severe high altitude-like retinopathy pathology with associated retinal
      hemorrhages. CONCLUSION: Altitude-related illnesses like high-altitude
      retinopathy result from rapid physiologic adaptation to altitude-induced hypoxia.
      These illnesses are typically experienced at altitudes above 3,000 m, with high
      altitude retinal hemorrhages observed above 4,270 m. The patient participated in
      no strenuous physical activity but had severe enough retinal hypoxia from
      chemotherapy-induced anemia and thrombocytopenia that he experienced visually
      significant retinal hemorrhages. The occurrence of high-altitude retinopathy in
      such patients could portend the development of high-altitude cerebral edema at
      lower altitudes than traditionally reported and without exposure to known risk
      factors. Therefore, funduscopic examination should be performed on patients with
      anemia and thrombocytopenia who are complaining of decreased vision after
      traveling at high altitude.

PMID- 25390813
TI  - Pressure-induced interlamellar stromal keratitis after vitreoretinal surgery.
AB  - PURPOSE: To describe a patient with pressure-induced interlamellar stromal
      keratitis after complicated vitreoretinal surgery, occurring 7 years after myopic
      laser in situ keratomileusis. METHODS: Case report and review of the literature.
      RESULTS: A 45-year-old man presented with increasing pain and blurring of vision
      in his left eye 3 weeks after vitreoretinal surgery for rhegmatogenous retinal
      detachment. This was associated with diffuse corneal stromal haze and raised
      intraocular pressure. An anterior segment optical coherence tomography revealed
      fluid between the laser in situ keratomileusis flap and the residual stromal bed.
      CONCLUSION: Pressure-induced interlamellar stromal keratitis can occur many years
      after laser in situ keratomileusis. The clinical presentation mimics that of
      diffuse lamellar keratitis, but corneal haze may be absent in the early stages.
      Once diagnosed, the intraocular pressure should be managed aggressively to
      prevent the development of irreversible glaucomatous optic neuropathy.

PMID- 25390814
TI  - Spectral domain optical coherence tomography characteristics of retained
      subretinal perfluoro-n-octane.
AB  - PURPOSE: To describe the spectral domain optical coherence tomography
      characteristics of retained subretinal perfluoro-n-octane (SR-PFO) after
      vitreoretinal surgery. METHODS: Consecutive patients referred for retained SR-PFO
      after pars plana vitrectomy for retinal detachment were prospectively evaluated
      with spectral domain optical coherence tomography. The clinical findings, fundus
      autofluorescence, spectral domain optical coherence tomography images, and
      anatomical outcomes, were reviewed. RESULTS: Three consecutive patients presented
      to the vitreoretinal service with history of retinal detachment and pervious
      vitrectomy with intraoperative PFO. Subretinal PFO bubbles were observed on
      clinical examination and imaging studies, including spectral domain optical
      coherence tomography. Case 1 had subfoveal PFO removal and developed a
      postoperative choroidal neovascular membrane. Case 2 had multiple foci of SR-PFO
      after giant retinal tear repair. Case 3 had superotemporal SR-PFO that remained
      stable for several years without migration or other associated pathology.
      CONCLUSION: Subretinal PFO appears as a low-reflectance spherical mass, often
      with a pinpoint focus of hyperreflectance at the apex of the bubble. Optical
      coherence tomography details beneath subretinal PFO appear relatively
      hyperreflectant compared to adjacent tissue. Long-term observation revealed
      preferential absence of the outer retinal layers with no nerve fiber layer
      erosion, subretinal inflammatory precipitates, or proliferative
      vitreoretinopathy. Some evidence of retinal pigment epithelial disruption was
      observed but seemed to remain stable or improve with observation. The authors
      suggest management involving follow-up with close observation in SR-PFO unless
      present in the subfoveal region. Choroidal neovascular membrane can occur after
      SR-PFO removal and may be successfully managed with intravitreal bevacizumab.

PMID- 25390815
TI  - Improved perfusion and intraretinal neovascularization after intravitreal
      bevacizumab injection in central vein occlusion.
AB  - PURPOSE: To report a case of intraretinal neovascularization in a patient with
      ischemic central venous occlusion. METHODS: Case report. RESULTS: An 18-year-old
      white man presented with painless decreased vision in the right eye. Slit-lamp
      and biomicroscopic examinations revealed 360 degrees  of neovascularization of
      the iris, venous tortuosity, severe retinal hemorrhages, cotton wool spots, and
      massive edema of the macula. CONCLUSION: This is the first report of observed
      intraretinal neovascularization after central vein occlusion. Treatment with
      photocoagulation and intravitreal bevacizumab injection promoted
      revascularization after 1 year.

PMID- 25390816
TI  - Cytomegalovirus retinitis after treatment with lenalidomide for multiple myeloma.
AB  - PURPOSE: To describe a case of cytomegalovirus retinitis in a patient after
      treatment with lenalidomide, a novel therapy in the treatment of multiple
      myeloma. METHODS: Descriptive case report of a 67-year-old man on Lenalidomide
      maintenance therapy for multiple myeloma, who presented with unilateral painless
      blurring of vision because of retinitis. RESULTS: Polymerase chain reaction of
      the vitreous sampling confirmed cytomegalovirus retinitis, although the patient's
      serum polymerase chain reaction was negative for cytomegalovirus. The patient was
      treated with ganciclovir with good effect. CONCLUSION: Cytomegalovirus retinitis
      is rare in immunocompetent patients and not commonly reported in myeloma
      patients. Given the increasing use of novel therapies such as Lenalidomide,
      unusual infections such as cytomegalovirus retinitis should be considered in
      patients with visual symptoms, even if they are considered to be immune competent
      at presentation.

PMID- 25390817
TI  - Choroidal lesions in neurofibromatosis detected by multispectral imaging.
AB  - BACKGROUND/PURPOSE: To describe the detection of multiple choroidal lesions in a
      patient with Type 1 neurofibromatosis using multispectral imaging. METHODS: A 25
      year-old woman diagnosed with Type 1 neurofibromatosis was examined with the
      Annidis-RHA system (Annidis Corp.). RESULTS: While conventional ophthalmoscopic
      imaging showed an unremarkable examination, multispectral imaging with red and
      infrared wavelengths evidenced numerous deep choroidal lesions. CONCLUSION:
      Multispectral imaging may detect the choroidal lesions of Type 1
      neurofibromatosis that are not easily seen with clinical examination or with
      other imaging modalities.

PMID- 25390818
TI  - Influence of Picual olive ripening on virgin olive oil alteration and stability
      during potato frying.
AB  - Ripening modifies oil attributes and composition. However, the influence of olive
      ripening on virgin olive oil (VOO) thermal oxidative stability on food-frying has
      not been studied yet. Oils from Picual olives of low (VOO1), medium (VOO2), and
      high (VOO3) ripeness were obtained, and their thermal oxidative stability during
      40 potato-fryings was tested. Unused VOO1 showed higher antioxidant content and
      oxidative stability than VOO2 and VOO3. Polar compounds (PC), oligomers, and
      altered fatty acid methyl esters (polar-FAME) increased, whereas linoleic acid,
      polyphenols, and tocopherols decreased in the three VOOs through frying. The
      alteration was lower in VOO1, followed by VOO2 (0.105, 0.117, and 0.042 g/100 g
      oil less of PC, oligomers and polar-FAME per frying, respectively, in VOO1 than
      in VOO3). In conclusion, VOO obtained from low-ripeness Picual olives should be
      preferred when frying fresh-potatoes due to its higher thermal and oxidative
      stability, permitting a higher number of potato-frying uses. 

PMID- 25390819
TI  - Repeat surgery after breast conservation for the treatment of stage 0 to II
      breast carcinoma: a report from the National Cancer Data Base, 2004-2010.
AB  - IMPORTANCE: Although complete excision of breast cancer is accepted as the best
      means to reduce local recurrence and thereby improve survival, there is currently
      no standard margin width for breast conservation surgery. As a result,
      significant variability exists in the number of additional operations or repeat
      surgeries patients undergo to establish tumor-negative margins. OBJECTIVE: To
      determine the patient, tumor, and facility factors that influence repeat surgery
      rates in US patients undergoing breast conservation surgery. DESIGN, SETTING, AND
      PATIENTS: Patients diagnosed as having breast cancer at a Commission on Cancer
      accredited center from January 1, 2004, through December 31, 2010, and identified
      via the National Cancer Data Base, a large observational database, were included
      in the analysis. A total of 316,114 patients with stage 0 to II breast cancer who
      underwent initial breast conservation surgery were studied. Patients who were
      neoadjuvantly treated or whose conditions were diagnosed by excisional biopsy
      were excluded. MAIN OUTCOMES AND MEASURES: Patient, tumor, and facility factors
      associated with repeat surgeries. RESULTS: A total of 241,597 patients (76.4%)
      underwent a single lumpectomy, whereas 74,517 (23.6%) underwent at least 1
      additional operation, of whom 46,250 (62.1%) underwent a completion lumpectomy
      and 28,267 (37.9%) underwent a mastectomy. The proportion of patients undergoing
      repeat surgery decreased slightly during the study period from 25.4% to 22.7% (P
      < .001). Independent predictors of repeat surgeries were age, race, insurance
      status, comorbidities, histologic subtype, estrogen receptor status, pathologic
      tumor size, node status, tumor grade, facility type and location, and volume of
      breast cancer cases. Age was inversely associated with repeat surgery, decreasing
      from 38.5% in patients 18 to 29 years old to 16.5% in those older than 80 years
      (P < .001). In contrast, larger tumor size was linearly associated with a higher
      repeat surgery rate (P < .001). Repeat surgeries were most common at facilities
      located in the Northeast region (26.5%) compared with facilities in the Mountain
      region, where only 18.4% of patients underwent repeat surgery (P < .001).
      Academic or research facilities had a 26.0% repeat surgery rate compared with a
      rate of 22.4% at community facilities (P < .001). CONCLUSIONS AND RELEVANCE:
      Approximately one-fourth of all patients who undergo initial breast conservation
      surgery for breast cancer will have a subsequent operative intervention. The rate
      of repeat surgeries varies by patient, tumor, and facility factors and has
      decreased slightly during the past 6 years.

PMID- 25390820
TI  - Magnetic structure of Sr2CuWO6.
AB  - Magnetic structure of the double perovskite Sr2CuWO6 was determined from neutron
      powder diffraction data. At 3 K the material is magnetically long-range ordered
      into a collinear antiferromagnetic structure described by a propagation vector k
      = (0, 1/2, 1/2) with the Cu(II) moments of 0.57(1) MUB parallel to the a-axis.
      The result is in agreement with our previous prediction (Vasala et al 2014 Phys.
      Rev. B 89 134419) based on electronic structure calculations, showing that the
      three-dimensional magnetic long-range order is caused by relatively strong
      antiferromagnetic next-nearest-neighbor interactions. 

PMID- 25390822
TI  - Oral preexposure prophylaxis to prevent HIV infection: clinical and public health
      implications.
AB  - This article reviews the use of combination emtricitabine (FTC)/tenofovir as
      preexposure prophylaxis (PrEP) for HIV-negative patients at high risk of
      acquiring HIV, including heterosexual men and women, men who have sex with men,
      and IV drug users. When used with classic prevention strategies such as condoms,
      PrEP has been found effective in reducing the risk of HIV transmission. 

PMID- 25390821
TI  - Mechanistic insight into the photoredox catalysis of anti-markovnikov alkene
      hydrofunctionalization reactions.
AB  - We describe our efforts to understand the key mechanistic aspects of the
      previously reported alkene hydrofunctionalization reactions using 9-mesityl-10
      methylacridinium (Mes-Acr(+)) as a photoredox catalyst. Importantly, we are able
      to detect alkene cation radical intermediates, and confirm that phenylthiyl
      radical is capable of oxidizing the persistent acridinyl radical in a fast
      process that unites the catalytic activity of the photoredox and hydrogen atom
      transfer (HAT) manifolds. Additionally, we present evidence that diphenyl
      disulfide ((PhS)2) operates on a common catalytic cycle with thiophenol (PhSH) by
      way of photolytic cleaveage of the disulfide bond. Transition structure analysis
      of the HAT step using DFT reveals that the activation barrier for H atom donation
      from PhSH is significantly lower than 2-phenylmalononitrile (PMN) due to
      structural reorganization. In the early stages of the reaction, Mes-Acr(+) is
      observed to engage in off-cycle adduct formation, presumably as buildup of PhS(-)
      becomes significant. The kinetic differences between PhSH and (PhS)2 as HAT
      catalysts indicate that the proton transfer step may have significant rate
      limiting influence. 

PMID- 25390823
TI  - Adhesion of alkane as a functional group on muscovite and quartz: dependence on
      pH and contact time.
AB  - The interactions between mineral surfaces and organic molecules in water control
      many processes in nature and in the production of modern materials. To improve
      the understanding of fluid-surface interactions, we investigated the interface
      behavior of quartz and muscovite, a model for clay minerals, in aqueous solutions
      where the pH and composition were controlled. We used atomic force microscopy
      (AFM) in chemical force mapping (CFM) mode to measure adhesion using tips
      functionalized with alkyl, -CH3. By combining adhesion forces measured as a
      function of pH, with data from streaming potential experiments and DLVO
      calculations, we were able to determine the surface charge density. We observed
      increased adhesion between the mineral surface and the hydrophobic tips as the
      contact time increased from 7 ms to ~2 s. The diffusion of dissolved ions takes
      time, and density functional theory (DFT) calculations did not indicate a strong
      hydration of the mineral surfaces. Therefore, we interpret that the loss of ions
      from the confined space between the tip and sample is a likely explanation of the
      correlation between the dwell time and adhesion. The maximum adhesion increase
      with dwell time for muscovite, i.e., 400 +/- 77 pN, was considerably larger than
      for quartz, 84 +/- 15 pN, which fits with the different surface structure and
      composition of the two minerals. We propose two mechanisms to explain these
      results: (1) cations that are structured in the solution and on the surface
      remain associated at the tip-sample interface initially but diffuse away during
      extended contact time and (2) adventitious carbon, the organic material that
      comes spontaneously from air and solution, can diffuse to the tip-sample
      interface during contact. This material decreases the surface energy by
      aggregating near the alkyl tip and increases adhesion between the tip and sample.

PMID- 25390824
TI  - Globe salvage using chemoreduction for advanced retinoblastoma in a glaucomatous
      eye with buphthalmos.
AB  - PURPOSE: To report globe salvage using chemoreduction (CRD) for advanced
      retinoblastoma in a glaucomatous eye with buphthalmos. METHODS: Case report.
      RESULTS: A 7-month-old girl presented with epiphora and buphthalmos in the right
      eye. She was found to have bilateral retinoblastoma. Classified as group E, the
      right eye exhibited a total retinal detachment and buphthalmos from secondary
      glaucoma. The left eye was classified as group B. Systemic workup revealed no
      metastatic disease. CRD was employed with future planned enucleation of the right
      eye. After six cycles of CRD and focal consolidating treatments, complete
      regression of retinoblastoma in both eyes was achieved. The right eye showed
      complete resolution of the retinal detachment and no active tumor or seeds at 18
      months follow-up, allowing for salvage of the eye. CONCLUSION: In this child with
      secondary glaucoma and buphthalmos from retinoblastoma, CRD provided complete
      tumor control and globe salvage.

PMID- 25390825
TI  - Echographic localization of periocular Carboplatin for treatment of advanced
      retinoblastoma.
AB  - PURPOSE: To study ocular ultrasonography as a means to effectively localize
      periocular carboplatin in patients with advanced retinoblastoma. METHODS: In a
      cases series, seven patients diagnosed with advanced retinoblastoma refractory to
      standard chemotherapy were treated with two to four periocular carboplatin
      injections. Echographic images were obtained before and after injection. RESULTS:
      The periocular carboplatin depot was a discrete homogeneous structure with lower
      internal reflectivity than the surrounding orbital tissue. The mean maximal
      juxtascleral height of the drug depot +/- SD was 3.3 +/-1.4 mm and was located
      directly posterior to the area of maximal intraocular tumor thickness in all
      seven patients. Moderate shadowing from calcification was present in one patient.
      Five patients had a pattern of a thinner pocket of drug visible after subsequent
      injections. CONCLUSIONS: Echography is a useful technique to study novel
      periocular drug delivery. It effectively images the drug in relation to the
      intraocular tumor, confirming the most effective drug placement for these
      resistant tumors.

PMID- 25390826
TI  - Pediatric nasopharyngeal carcinoma with retinal metastasis.
AB  - PURPOSE: To report an unusual case of nasopharyngeal carcinoma (NPC) metastatic
      to the lungs and retina. To our knowledge, this is the first report of retinal
      metastasis from NPC. DESIGN: Observational case report. METHODS: We studied the
      case of a 15-year-old boy who had been recently diagnosed with metastatic NPC and
      was referred for evaluation of a suspicious retinal lesion in the right eye.
      RESULTS: Clinical examination and fundus photography showed an amelanotic, 1-disk
      area infiltration in the retina along the inferotemporal arcade that was
      suggestive of metastatic disease. The lesion was small and irregularly shaped by
      echographic examination, and a nodular area of retinal thickening was seen by
      optical coherence tomography. Pathologic analysis of lung biopsy and nasopharynx
      biopsy specimens revealed undifferentiated NPC. CONCLUSIONS: Retinal metastases
      need to be considered in the differential diagnosis of patients presenting with
      NPC and vision changes.

PMID- 25390827
TI  - Polypoidal choroidal vasculopathy in association with choroidal nevus.
AB  - PURPOSE: To report an association between polypoidal choroidal vasculopathy (PCV)
      and choroidal nevus in two patients. METHODS: Two patients with subretinal
      exudation associated with a choroidal nevus had a complete ophthalmologic
      examination, slit-lamp biomicroscopy, color fundus photography, fluorescein
      angiography (FA), and indocyanine green angiography (ICG). RESULTS: In the two
      eyes of the two patients with choroidal nevus, choroidal neovascularization with
      PCV-like characteristics was detected by ICG angiography. CONCLUSIONS: PCV-like
      vascular changes can be associated with choroidal nevus, and ICG can help
      delineate the nature of the neovascularization in patients with choroidal nevus.

PMID- 25390828
TI  - Simultaneous multiple branch retinal artery occlusions after diagnostic cardiac
      catheterization.
AB  - PURPOSE: We describe a 53-year-old man with a decrease in visual acuity in the
      left eye 2 weeks after diagnostic cardiac catheterization. DESIGN: Interventional
      case report. METHODS: A 53-year-old man with a decrease in visual acuity in the
      left eye 2 weeks after diagnostic cardiac catheterization underwent
      ophthalmoscopic, angiographic, and laboratory evaluations. Both funduscopy and
      fluorescein angiography confirmed the diagnosis of simultaneous multiple branch
      retinal artery occlusions in the left eye. RESULTS: The left eye had a mildly
      positive (1+) relative afferent pupillary defect. Slit-lamp biomicroscopy was
      unremarkable except for 2+ nuclear cataract bilaterally. Intraocular pressure was
      12 mmHg in the right eye and 11 mmHg in the left eye by applanation tonometry.
      Funduscopy revealed a normal right eye. CONCLUSION: This case report of multiple
      branch retinal artery occlusions due to cholesterol embolus after diagnostic
      cardiac catheterization is extremely rare. Visual symptoms after cardiac
      catheterization should alert both ophthalmologists and cardiologists to this
      potential post-cardiac catheterization complication.

PMID- 25390829
TI  - Ophthalmic artery occlusion in relapsing polychondritis.
AB  - PURPOSE: To describe ophthalmic artery occlusion in a patient with relapsing
      polychondritis. METHODS: Observational case report RESULTS: : An acute episode of
      relapsing polychondritis caused ophthalmic artery occlusion with resultant visual
      acuity of no light perception. CONCLUSION: Ophthalmic artery occlusion can occur
      in patients with relapsing polychondritis. Patients with relapsing polychondritis
      need close follow-up to exclude severe vascular disease.

PMID- 25390830
TI  - Arteriolar macroaneurysm on the optic disk associated with branch retinal vein
      occlusion.
AB  - PURPOSE: To report a case of an arteriolar macroaneurysm on the optic disk
      associated with branch retinal vein occlusion (BRVO). METHOD: Patient chart
      review. PATIENT: An 80-year-old man presented with a retinal arteriolar
      macroaneurysm on the optic disk on the root of a papillomacular vein, which
      caused BRVO. RESULTS: Eight months later, the macroaneurysm shrank spontaneously
      and became fibrous tissue. The hemorrhage and edema due to BRVO resolved.
      DISCUSSION: We speculate that the macroaneurysm was located on and compressed the
      epipapillary portion of the papillomacular vein, resulting in BRVO. With
      spontaneous involution of the macroaneurysm, the compression resolved, and the
      clinical findings improved.

PMID- 25390831
TI  - INTERFERON-beta-ASSOCIATED RETINOPATHY.
AB  - BACKGROUND: Interferon-associated retinopathy is a rare complication of
      interferon treatment. It has been well described with the use of interferon
      alpha. METHODS: This study reports a retrospective case series of interferon-beta
      associated retinopathy in three patients that were being treated for multiple
      sclerosis. RESULTS: All cases were characterized by cotton-wool spots or
      peripheral microaneurysms. One central retinal artery occlusion was observed
      associated with interferon-beta treatment. Findings improved spontaneously in two
      of three cases; all three patients elected to continue interferon treatment.
      CONCLUSION: Patients being treated with interferon-beta should have periodic
      fundus examinations to determine if they have evidence of interferon-associated
      retinopathy.

PMID- 25390832
TI  - Endogenous nocardial chorioretinitis in an immunocompetent patient.
AB  - PURPOSE: To describe the presentation and management of an immunocompetent
      patient with endogenous Nocardia chorioretinitis. METHODS: A previously healthy
      55-year-old woman presented with reduced vision and metamorphopsia after
      accidental inhalation of Nocardia organisms from planting soil. She developed
      systemic nocardiosis with pulmonary and cerebellar involvement as well as
      bilateral chorioretinitis. Ocular infection resulted in choroidal
      neovascularization, which was successfully treated with intravitreal
      triamcinolone and thermal laser photocoagulation. DISCUSSION: This patient is one
      of only a few immunocompetent individuals to develop endogenous nocardial
      chorioretinitis. Systemic antibiotic treatment and local laser therapy for
      subsequent choroidal neovascularization were effective in management of this
      case.

PMID- 25390833
TI  - Optical coherence tomography of west african crystalline maculopathy.
AB  - PURPOSE: To describe a case of West African crystalline maculopathy and the
      optical coherence tomography (OCT) findings. METHODS: A 47-year-old West African
      woman presented with bilateral yellow-green refractile crystals clustered in the
      fovea. She had proliferative diabetic retinopathy and a long history of chewing
      kola nuts. Given her history and clinical examination findings, a diagnosis of
      West African crystalline maculopathy was made. RESULTS: OCT revealed that the
      foveal crystals were located in the innermost layers of the retina. CONCLUSIONS:
      OCT findings, along with history and examination, can be helpful in confirming
      the diagnosis of West African crystalline maculopathy.

PMID- 25390834
TI  - Frosted branch angiitis secondary to herpes simplex virus infection progressing
      to acute retinal necrosis.
AB  - PURPOSE: To describe a case of frosted branch angiitis secondary to herpes
      simplex virus type 2 infection that progressed to acute retinal necrosis.
      METHODS: The medical records and clinical photographs were reviewed for a patient
      with frosted branch angiitis that progressed to acute retinal necrosis. RESULTS:
      The patient rapidly developed acute retinal necrosis followed by rhegmatogenous
      retinal detachment. Polymerase chain reaction analysis of the vitreous was
      positive for herpes simplex virus type 2. DISCUSSION: Frosted branch angiitis is
      a clinical sign that may represent active viral disease capable of progressing to
      acute retinal necrosis.

PMID- 25390835
TI  - Spontaneous resolution of retinal angiomatous proliferation.
AB  - PURPOSE: To describe a case of spontaneous resolution of retinal angiomatous
      proliferation (RAP) in a patient with age-related macular degeneration. METHODS:
      A 67-year-old woman complained about progressive visual loss in the right eye.
      Visual acuity was 20/50 in the right eye and 20/20 in the left eye. Detailed
      ophthalmoscopic examination, fluorescein angiography, indocyanine green
      angiography, and optical coherence tomography of the right eye were performed.
      RESULTS: Fundus examination of the right eye revealed a small extrafoveal
      hemorrhage with a few hard exudates around a serous retinal elevation.
      Fluorescein angiography showed late-phase staining with an area of
      hyperfluorescence interpreted as occult neovascularization. The middle-phase
      indocyanine green angiograms showed a focal "hot spot" with late intraretinal
      leakage. Optical coherence tomography performed through the hot spot shown by
      indocyanine green angiography demonstrated a localized area of increased
      intraretinal reflectivity and subfoveal optically empty areas corresponding to
      serous retinal detachment. The patient was diagnosed with stage II RAP. Treatment
      was recommended, but the patient was lost to follow-up. Five months later, the
      patient returned to our department with visual acuity of 20/30 in the involved
      eye. Spontaneous resolution of the angiographic leakage shown by both fluorescein
      angiography and indocyanine green angiography and restoration of the normal
      retinal layers by optical coherence tomography were observed. CONCLUSIONS: To our
      knowledge, this is the first known case in which angiographic and optical
      coherence tomography findings depicted the spontaneous regression of RAP.

PMID- 25390836
TI  - Bilateral choroidal neovascularization in birdshot retinochoroidopathy treated
      with intravitreal injections of triamcinolone and bevacizumab.
AB  - PURPOSE: To describe a patient with birdshot retinochoroidopathy (BRC) with
      bilateral choroidal neovascularization (CNV) who was treated with intravitreal
      injection of bevacizumab and antiinflammatory medications. METHOD: Interventional
      case report. PATIENT: A 35-year-old woman with bilateral CNV associated with BRC.
      RESULTS: The patient was treated with intravitreal injection of triamcinolone,
      photodynamic therapy, and intravitreal injection of bevacizumab in one eye, while
      the fellow eye was treated with intravitreal injection of triamcinolone.
      Immunosuppressive therapy was performed in the course of the treatment. Not only
      did the neovascularization respond, but the birdshot lesions vanished as well.
      DISCUSSION: BRC can have secondary CNV that, as in the current case, responds
      favorably to treatment. We serendipitously observed regression of the choroidal
      inflammatory lesions with intravitreal injection of triamcinolone.

PMID- 25390837
TI  - Subretinal triamcinolone acetonide associated with improvement of cystoid macular
      edema in a patient with retinitis pigmentosa.
AB  - PURPOSE: To report a case of traumatic displacement of intravitreal triamcinolone
      acetonide into the subretinal space. METHODS: Single case report. RESULTS: We
      describe a 17-year-old boy with retinitis pigmentosa and severe, persistent
      cystoid macular edema with foveal cysts resistant to surgical intervention who
      had marked clinical improvement after traumatic displacement of intravitreal
      triamcinolone acetonide into the subretinal space. CONCLUSION: Subretinal
      delivery of triamcinolone acetonide may be more effective than preretinal steroid
      administration in reducing foveal cysts, particularly in retinitis pigmentosa. In
      this case, the duration of triamcinolone acetonide in the subretinal space seemed
      to be on the order of 3 months.

PMID- 25390838
TI  - Vitelliform macular detachment associated with Basal laminar drusen is
      unresponsive to vascular endothelial growth factor blockade.
AB  - PURPOSE: To determine whether vascular endothelial growth factor (VEGF) mediates
      the leakage in basal laminar drusen (BLD)-associated vitelliform macular
      detachment (VMD) and whether VEGF blockade can improve visual function in
      affected eyes. METHODS: Interventional case report. PATIENT: A 46-year-old woman
      presented with decreased visual acuity in the right eye and BLD-associated VMD.
      RESULTS: There was no improvement in visual acuity, fundus appearance, or
      findings of fluorescein angiography and optical coherence tomography after two
      intravitreal injections of anti-VEGF agents, suggesting that the exudation is not
      VEGF mediated. CONCLUSION: Ophthalmologists should distinguish BLD-associated
      VMDs from age-related macular degeneration-associated choroidal
      neovascularization to avoid exposing patients to the risk of unnecessary
      intravitreal injections.

PMID- 25390839
TI  - Angioid streaks and optic nerve head drusen in hyperphosphatemic familial tumoral
      calcinosis.
AB  - PURPOSE: To describe a patient with angioid streaks and optic nerve head drusen
      associated with familial tumoral calcinosis (FTC). DESIGN: Retrospective,
      observational case report. METHODS: The patient's records were reviewed. RESULTS:
      After receiving blunt trauma to the head, the patient presented with loss of
      vision in the left eye. Fundus examination revealed bilateral angioid streaks,
      optic nerve head drusen, and choroidal ruptures associated with subretinal
      hemorrhages. Subsequent physical, laboratory, and radiologic examinations
      revealed periarticular calcification, elevated serum phosphate levels, and normal
      calcium levels, consistent with FTC. CONCLUSIONS: FTC should be considered in the
      differential diagnosis for patients presenting with angioid streaks and optic
      nerve head drusen.

PMID- 25390840
TI  - Vitreoretinal surgery in advanced coats disease.
AB  - PURPOSE: To report the outcomes of vitreoretinal surgery for a patient with total
      retinal detachment and a subretinal nodule associated with Coats disease (CD).
      METHODS: A 20-year-old woman stage 3B CD underwent vitreoretinal surgery with
      triamcinolone acetonide-assisted pars plana vitrectomy, limited retinotomy,
      removal of the subretinal nodule and membrane, endolaser photocoagulation, and
      silicone oil tamponade. The surgical outcomes were observed. RESULTS: Retinal
      attachment was achieved after vitreoretinal surgery, removal of the subretinal
      membrane, and endoresection of the subretinal fibrous nodule. No intraoperative
      or postoperative complications occurred due to the surgical technique. The retina
      remained attached during the postoperative follow-up period of 6 months.
      CONCLUSION: Vitreoretinal surgery is an effective surgical technique that
      provides successful reattachment of the retina and enables endoresection of the
      subretinal fibrous nodule in eyes with advanced CD. It also prevents the
      devastating intraocular complications leading to enucleation.

PMID- 25390841
TI  - Histologic and immunohistochemical features of a vitreous cyst.
AB  - PURPOSE: To report the histologic and immunohistochemical features of a
      congenital vitreous cyst. METHODS: Interventional case report with
      immunohistochemical correlation. A 58-year-old woman with known vitreous cyst
      since childhood had an enlarging visual floater. The vitreous cyst was removed by
      pars plana vitrectomy and central vision was restored. RESULTS: Pathology
      confirmed a vitreous cyst derived from neural and glial tissue and consistent
      with retinal origin. CONCLUSIONS: Congenital vitreous cysts, derived from neural
      and glial tissue, can be safely removed using pars plana vitrectomy.

PMID- 25390842
TI  - Retinal pigment epithelial tear after subretinal rtpa and intravitreal air for
      the displacement of a large submacular hemorrhage.
AB  - PURPOSE: The authors report a case of retinal pigment epithelial (RPE) tear
      following pars plana vitrectomy (PPV), subretinal recombinant tissue plasminogen
      activator (rt-PA), and intravitreal gas administration for the displacement of
      large submacular hemorrhage. METHODS: A patient with a large submacular
      hemorrhage secondary to neovascular age-related macular degeneration (AMD)
      received a subretinal rt-PA injection and intravitreal air installation after
      PPV. Ophthalmic examination included standardized visual acuity testing and
      fluorescein angiography. PATIENTS: One patient from the authors' outpatient
      clinic. RESULTS: Baseline visual acuity of the eye was 20/160. Ophthalmoscopy
      showed a predominantly hemorrhagic lesion in the macula. Ophthalmoscopy and
      fluorescein angiography 2 weeks after the surgery revealed a RPE tear.
      Postoperative visual acuity was 20/1000. CONCLUSIONS: This case demonstrates that
      a RPE tear is a possible complication of the procedure of subretinal rt-PA and
      intravitreal air tamponade after PPV for the displacement of a large submacular
      hemorrhage secondary to neovascular AMD. The surgeon has to be aware about this
      complication and should inform the patient before surgery.

PMID- 25390843
TI  - Guillotine performance: duty cycle analysis of vitrectomy systems.
AB  - PURPOSE: To evaluate the duty cycle of different vitrectomy cutters and classify
      their blade movement. METHODS: A precise weighing (0.01 g) high speed (2
      samples/s) balance was used to study the 20-gauge and 25-gauge Bausch & Lomb
      Lightning-Millenium (St. Louis, MO), the 20-gauge (1500 cpm) and the 25-gauge
      Alcon Accurus (Fort Worth, TX), the 20-gauge Alcon Innovit, and the 23-gauge DORC
      (Netherlands) cutters. The weight of balanced saline solution (BSS) was recorded
      in real time using LabView software and then translated into a graph of volume
      removed versus time. Variable cut rates and vacuum pressures were analyzed in
      vitreous and BSS. A high-speed (400 frames/s) camera was used to record cutting
      for each condition. RESULTS: Three types of duty cycle were investigated:
      parabolic incomplete (pneumatic), sinusoid (electric), and trapezoid (double
      pneumatic). The parabolic incomplete and trapezoid had a decreased duty cycle at
      1500 cuts per minute when it was compared to 600 cuts per minute. The sinusoid
      had no statistical difference between cut rates. CONCLUSIONS: Systems showed
      different performances of duty cycle. This new classification will be useful for
      improved understanding of vitrectomy in these different systems.

PMID- 25390844
TI  - Wandering nematode in the vitreous cavity.
AB  - BACKGROUND: Bancroftian filariasis is focally endemic in Egypt. There have been
      many reports of intraocular filariasis; the question of why one filarial nematode
      should cause ocular disease while another does not may be related to the behavior
      of the microfilaria and the location of the cross-reacting ocular antigen.
      METHODS: A 35-year-old woman with a white worm approximately 3 disk diameters in
      length penetrating the left macula, moving in the vitreous cavity, with a part of
      its length in the vitreous cavity while the rest was embedded subretinally, is
      described. Pars plana vitrectomy was performed and the worm was aspirated
      successfully. RESULTS: Parasitologic study of the aspirated worm identified
      juvenile Wuchereria bancrofti. Ivermectin 150 MUg/kg was given orally to the
      patient after identification of the worm. Six weeks later, the patient's visual
      acuity had improved to 20/200. CONCLUSION: Intravitreal parasites should be
      surgically removed as soon as possible.

PMID- 25390845
TI  - Tractional retinal detachment after intravitreal injection of bevacizumab in
      proliferative diabetic retinopathy.
AB  - PURPOSE: To assess the short-term complications of a single dose of intravitreal
      bevacizumab in patients with proliferative diabetic retinopathy (PDR). METHODS:
      Retrospective review of 343 patients with PDR who were treated with intravitreal
      injection of bevacizumab (2.5 mg/0.1 mL). RESULTS: Five patients (1.45%)
      presented tractional retinal detachment 1 to 6 weeks (mean 3 weeks) after
      intravitreal injection. All cases underwent pars plana vitrectomy, removal of all
      epiretinal fibrovascular membranes, further endolaser panretinal
      photocoagulation, and silicone tamponade. CONCLUSION: Tractional retinal
      detachment may occur in a short time post intravitreal injection of bevacizumab
      in patients with proliferative diabetic retinopathy with extensive areas of
      ischemia and fibrovascular proliferations, and may require prompt vitreoretinal
      surgery.

PMID- 25390846
TI  - A simple way to remove miragel explants after long-term inflammation and
      extrusion.
AB  - PURPOSE: To report three cases of exposure of Miragel (Medical Instruments
      Research Associates, Waltham, MA) implants many years after buckling surgery and
      a new surgical technique to avoid significant fragmentation and achieve safe and
      effective removal of the exposed implants. METHODS: Retrospective interventional
      series of three cases. RESULTS: Many years after the initial retinal detachment
      surgery, Miragel explants can be exposed, causing inflammation. Their removal can
      be difficult due to increased fragility. CONCLUSION: We have developed a simple
      and safe technique to remove extruded Miragel explants, reducing the risk of
      fragmentation.

PMID- 25390847
TI  - Viscoelastic agent retention and failed macular hole surgery.
AB  - PURPOSE: To describe the retention of a viscoelastic agent as a possible cause of
      failed macular hole surgery. METHODS AND PATIENTS: Three consecutive patients
      underwent macular hole surgery. A bubble of viscoelastic agent was used to
      prevent contact between indocyanine green dye and retinal pigment epithelium
      cells. RESULTS: Macular hole repair failed in all three cases. After a second
      surgery the holes closed successfully. CONCLUSION: The use of a dispersive
      viscoelastic agent to avoid indocyanine green toxicity in macular hole surgery
      may prevent the closure of the hole.

PMID- 25390848
TI  - Congenital simple hamartoma of the retinal pigment epithelium with a full
      thickness macular hole.
AB  - BACKGROUND: Congenital simple hamartoma of the retinal pigment epithelium
      (CSHRPE) is a rare tumor that, to our knowledge, has not been previously reported
      as being associated with a full-thickness macular hole. METHODS: We report a case
      of a CSHRPE associated with a full-thickness macular hole. Findings of funduscopy
      and optical coherence tomography are described. RESULTS: A 10-year-old boy
      presented with visual acuity of 20/80 in the right eye. Funduscopy revealed a
      juxtafoveal pedunculated, well-circumscribed, darkly pigmented lesion measuring
      one third of a disk diameter. There was an associated full-thickness macular hole
      that separated the main dark mass nasally from a linear pigmented lesion. Optical
      coherence tomography showed a mass with optical shadowing and confirmed the
      presence of a full-thickness macular hole surrounded by intraretinal cystic
      edema. No evidence of a posterior vitreous detachment or significant epiretinal
      membrane was seen. CONCLUSION: We observed a full-thickness macular hole with a
      CSHRPE in a 10-year-old boy. The CSHRPE may have induced tangential traction
      along the posterior hyaloid or abnormal anteroposterior traction with foveal
      dehiscence. It is possible that exudation from the lesion into the vitreous
      cavity may result in vitreous changes with premature liquefaction and
      degenerative alterations that may induce abnormal vitreous adhesion and traction.
      Optical coherence tomography did not show evidence of such changes.

PMID- 25390849
TI  - Macular hole with epiretinal membrane after triamcinolone-assisted vitrectomy for
      proliferative diabetic retinopathy.
AB  - BACKGROUND: We described three cases of macular holes with an epiretinal membrane
      that developed after triamcinolone-assisted vitrectomy for proliferative diabetic
      retinopathy (PDR). CASE REPORTS: In case 1, vitrectomy was performed for vitreous
      hemorrhage and tractional retinal detachment. In case 2 and 3, vitrectomy was
      performed for vitreous hemorrhage. Triamcinolone acetonide was used to visualize
      the vitreous during surgery and the posterior vitreous cortex was completely
      removed. Macular hole occurred 18, 9, and 1 months after the initial vitrectomy
      in cases 1, 2, and 3, respectively. In all cases, additional surgery was
      performed and closure of the macular hole was achieved. CONCLUSION: Macular hole
      with epiretinal membrane occurred after triamcinolone-assisted vitrectomy for PDR
      in three cases. Hole closure was achieved after additional vitreous surgery.
      Epiretinal membrane and macular hole might occur even in cases in which the
      posterior vitreous cortex has been removed completely during triamcinolone
      assisted vitrectomy for PDR.

PMID- 25390850
TI  - Macular hole secondary to a subretinal hemorrhage.
AB  - PURPOSE: To report a case of a full-thickness macular hole developing after a
      subretinal hemorrhage in a patient with age-related macular degeneration (AMD).
      METHODS AND PATIENTS: A 75-year-old woman was followed with sequential
      fluorescein angiography and optical coherence tomography from her initial
      presentation to postoperative follow-up. RESULTS: The patient presented with
      sudden visual loss in her left eye. Fluorescein angiography showed AMD with a
      significant subretinal hemorrhage. Five months later, the visual acuity of her
      left eye had further deteriorated and examination revealed that a full-thickness
      macular hole had developed. Surgical treatment achieved complete anatomic closure
      of the macular hole with significant improvement in the visual acuity of the
      affected eye. CONCLUSIONS: A full-thickness macular hole may rarely develop
      following a subretinal hemorrhage. In such cases, surgical closure can improve
      the functional outcome.

PMID- 25390851
TI  - Successful combined photodynamic and intravitreal avastin therapy for subfoveal
      choroidal neovascularization in a child.
AB  - PURPOSE: To report the results of combined photodynamic therapy with verteporfin
      and intravitreal Avastin delivered on the same day in the treatment of juvenile
      subfoveal choroidal neovascularization. METHODS: Photodynamic therapy with
      Visudyne at standard fluence rates and intravitreal Avastin were successfully
      completed under topical anesthesia in a single day treatment session in an 11
      year-old girl with subfoveal choroidal neovascularization. PATIENT: A cooperative
      11-year-old girl noted sudden vision loss in her right eye with a previous
      history of a small nonspecific extrafoveal inferior scar, and was noted to have
      developed an acute subfoveal choroidal neovascular membrane. RESULTS: The
      subfoveal choroidal neovascular membrane regressed without any additional therapy
      or recurrence over an 18-month period and with recovery of 20/20 vision. There
      were diffuse mild pigmentary changes in the region of the previous choroidal
      neovascularization. CONCLUSION: Choroidal neovascularization in juvenile patients
      may respond well to a combined photodynamic and intravitreal Avastin therapy
      delivered in a single day session with excellent recovery of vision and without
      the need for frequent multiple treatments, which would be difficult in this age
      group.

PMID- 25390852
TI  - Photodynamic therapy and vitrectomy for a large optic nerve hemangioma with
      neovascularization and retinal detachment: a clinicopathologic correlation.
AB  - PURPOSE: To report the clinicopathologic correlation of a young man with a von
      Hippel-Lindau disease-associated peripapillary hemangioblastoma and its
      satisfactory response to a combination of photodynamic therapy (PDT) and
      vitrectomy. DESIGN: Clinicopathologic correlation. METHODS: We studied the case
      of a 14-year-old boy with an optic nerve mass and large inferior exudative
      retinal detachment complicated by a significant tractional component from
      extensive secondary neovascularization over the lesion. RESULTS: A juxtapapillary
      hemangioblastoma with secondary neovascularization was documented by clinical
      examination, fundus photography, and optical coherence tomography. A von Hippel
      Lindau gene mutation was detected. The patient responded satisfactorily to a
      combination of PDT and vitrectomy. CONCLUSIONS: A staged approach to treatment of
      peripapillary hemangioblastoma with a combination of PDT and vitrectomy may be
      favorable to therapy with one modality.

PMID- 25390853
TI  - Pupillary block glaucoma in phakic eyes using 5000 centistoke silicone oil.
AB  - PURPOSE: To describe pupillary block glaucoma in phakic patients undergoing
      vitrectomy and 5000 centistoke silicone oil injection. DESIGN: Observational case
      reports. METHODS: Vitrectomy and higher-viscosity silicone oil injection was
      performed in two phakic patients with proliferative diabetic retinopathy.
      RESULTS: Both patients developed a pupillary block in the early postoperative
      period (1 week and 1 month after surgery). Unnoticed zonulysis during surgery,
      thought to be the main contributory cause, allowed access of the silicone oil
      between the iris and the lens. Although higher-viscosity silicone oil was used in
      both cases, an acute glaucoma developed. An inferior iridotomy was performed,
      resulting in a temporary resolution of the pupillary block. CONCLUSION:
      Vitreoretinal surgeons should be aware of silicone-induced pupillary block
      glaucoma in phakic eyes, even when higher-viscosity silicone oils are used.

PMID- 25390854
TI  - Central serous chorioretinopathy associated with unusual routes of steroid
      administration.
AB  - PURPOSE: To report three cases in which unusual routes of administration were
      associated with subsequent central serous chorioretinopathy (CSR). All three
      cases occurred in patients who were being treated for dermatologic conditions.
      METHODS: Retrospective review of three cases of patients who presented with a
      diagnosis of CSR and use of steroids in an unusual route for treatment of various
      dermatologic conditions (intradermal injection to the scalp for keloids, topical
      cream for psoriasis, and topical solution for cradle cap). RESULTS: Patient 1 had
      complete resolution and restoration of baseline visual acuity at the follow-up
      examination. This patient had no further injections to his keloids. Patient 2
      drastically decreased the dose of topical cream and had resolution of symptoms.
      Patient 3 discontinued use of the steroid solution and had no new episodes of
      visual decline. CONCLUSION: This case series suggests that occult steroid use
      should be suspected for patients presenting with CSR who are concurrently being
      treated for dermatologic conditions. The knowledge gained from this thorough
      history is vital to the management and long-term counseling of the patient.

PMID- 25390855
TI  - Interferon induced sarcoid uveitis with papillitis and macular edema.
AB  - PURPOSE: To describe the ocular manifestations of interferon induced sarcoidosis.
      METHODS: Observational case report. RESULTS: A 42-year-old woman with hepatitis C
      developed papillitis and macular edema together with cutaneous lesions 3 months
      after starting interferon and ribavirin therapy. The therapy was stopped. After
      17 months of observation, visual acuity remained stable and papillitis and
      macular edema persisted. The patient was finally treated with sub-tenon's
      repository methyl prednisolone in the left eye which significantly resolved both
      macular edema and papillitis and also improved vision. CONCLUSION: Interferon
      induced sarcoidosis is a new entity and can have ocular manifestations such as
      uveitis and papillitis as one of the presenting features, which is not common.

PMID- 25390856
TI  - Congenital x-linked retinoschisis: a novel approach for management of a large
      schitic cavity overhanging the macula.
AB  - PURPOSE: To describe a novel surgical technique used in the management of a
      patient with congenital X-linked juvenile retinoschisis who presented with a
      schitic cavity overhanging the macula. METHODS: The patient underwent controlled
      external fluid drainage and laser photocoagulation along with intravitreal gas
      injection. RESULTS: No intraoperative complication was noted. Postoperatively,
      the schitic cavity collapsed, the overhang resolved, and visual acuity improved.
      CONCLUSION: External drainage is a promising novel technique for the management
      of patients with congenital X-linked juvenile retinoschisis who have peripheral
      retinoschisis overhanging the macula.

PMID- 25390857
TI  - Fine-tuning the structures of chiral diamine ligands in the catalytic asymmetric
      aldol reactions of trifluoromethyl aromatic ketones with linear aliphatic
      ketones.
AB  - In this work, we thoroughly investigated the effect of structural differentiation
      of a series of N,N-disubstituted chiral diamine ligands on the catalytic
      asymmetric aldol reactions between trifluoromethyl ketones and linear aliphatic
      ketones for the construction of chiral trifluoromethyl tertiary alcohols. A
      highly efficient primary-tertiary diamine ligand derived from (1R,2R)-1,2
      diphenylethylenediamine was developed, which catalyzed the reactions with up to
      99% yield and up to 94% enantioselectivity in the presence of p-toluenesulfonic
      acid (TsOH) using toluene as solvent. 

PMID- 25390858
TI  - Intraoperative management of posterior capsular rupture.
AB  - PURPOSE OF REVIEW: Posterior capsular rupture (PCR) and vitreous loss are
      inevitable complications encountered in cataract surgery across all levels of
      surgical experience and in spite of technological advances to improve safety.
      Thus, cataract surgeons must always be prepared to practice safe and effective
      intraoperative management strategies for capsular rupture. RECENT FINDINGS: Novel
      approaches for lens fragment removal, vitrectomy, and lens implantation have
      expanded the available options for cataract surgery in the setting of an open
      posterior capsule. Intraoperative PCR management strategies should prioritize
      safety and strive to minimize vitreous traction, stabilize anterior chamber
      volume, maintain capsular and zonular integrity, and protect the corneal
      endothelium and other anterior segment structures. SUMMARY: With appropriate
      management of PCR and vitreous, surgeons may still deliver safe and satisfactory
      visual outcomes for modern cataract surgery.

PMID- 25390859
TI  - Small pupil and cataract surgery.
AB  - PURPOSE OF REVIEW: Presence of a small pupil is still considered a major
      challenge for cataract surgeons. Appropriate mydriasis and maintaining it is of
      paramount importance to prevent potential serious complications. Recently, more
      interventions and instruments are available for the cataract surgeons to deal
      with these challenging cases. The intention of this review is to discuss the
      preoperative and intraoperative considerations and techniques for cataract
      surgery in small pupil and related conditions and to discuss new developments in
      management of small pupil in femtosecond laser-assisted cataract surgery. RECENT
      FINDINGS: There are new techniques and pharmaceuticals available to cataract
      surgeons in the setting of small pupil. Intracameral ketorolac may soon be
      available to maintain mydriasis and to control pain and inflammation. Malyugin
      ring has been added to pupil expansion rings and has already been used for small
      pupil in different settings. In femtosecond laser-assisted cataract surgery,
      presence of a small pupil can now be managed by applying intracameral mydriatics
      and intraocular devices successfully. SUMMARY: Accurate preoperative examinations
      adjunct with intraoperative use of appropriate pharmacologic and mechanical
      devices can yield favorable outcomes in cataract surgery with a small pupil.

PMID- 25390860
TI  - Continuation of anticoagulant and antiplatelet therapy during phacoemulsification
      cataract surgery.
AB  - PURPOSE OF REVIEW: The objective of this review is to evaluate the result of
      cataract surgery in patients continuing antiplatelet and/or anticoagulant
      treatment. RECENT FINDINGS: The number of elderly patients using anticoagulant
      and antiplatelet treatment in prevention of venous thromboembolism has
      significantly increased in recent years. It was believed for many years that
      those patients might be at higher risk for complications during ocular surgery.
      Thus, different strategies were proposed to prevent these complications,
      including discontinuation of anticoagulants, dose reduction, or low-molecular
      weight heparin replacement. We performed a PubMed search over a period of 7 years
      (2007-2013) about possible intraoperative and postoperative complications in
      patients receiving anticoagulant and/or antiplatelet therapy at the time of
      cataract surgery. No significant increase in intraoperative or postoperative
      complications has been identified. SUMMARY: Phacoemulsification of uncomplicated
      cataracts with intraocular lens implantation can be performed safely in high-risk
      patients, taking both anticoagulants and antiplatelet drugs when topical
      anesthesia is administered and cataract surgery is performed through a clear
      corneal incision by a skilled surgeon.

PMID- 25390861
TI  - All about capsular tension rings.
AB  - PURPOSE OF REVIEW: To discuss capsular tension devices and recent evidence
      regarding their use. RECENT FINDINGS: The capsular tension ring, modified
      capsular tension ring, and capsular tension segment are well established tools
      for use during phacoemulsification when zonular instability is present. Recent
      research has provided additional evidence of their benefits in decreasing
      intraoperative and postoperative complications. SUMMARY: Endocapsular support
      devices allow for cataract surgery success in the setting of zonular instability.

PMID- 25390862
TI  - Femtosecond laser-assisted cataract surgery in residency training.
AB  - PURPOSE OF REVIEW: To examine the current state of femtosecond laser-assisted
      cataract surgery (FLACS) with a focus on its incorporation into resident surgical
      education. RECENT FINDINGS: To date, there are no published data on FLACS in
      residency training programs. Teaching FLACS concurrently with manual cataract
      surgery can theoretically allow a trainee to become proficient in both domains
      and to navigate the complexities and complications of both procedures in a
      dedicated learning environment. SUMMARY: Early reports from completed projects at
      our institution suggest that incorporating FLACS into residency education is
      successful and well tolerated. The procedure appears to have a similar safety
      profile and delivers similar refractive results compared with conventional
      phacoemulsification cataract surgery, even during the initial surgical learning
      curve. More research needs to be carried out on the safety profile and outcomes
      of resident performed FLACS and its ultimate role in trainee education.

PMID- 25390863
TI  - Invited commentary: on immediately loaded fixed maxillary prostheses.

PMID- 25390864
TI  - Vertical marginal gap evaluation of conventional cast and computer numeric
      controlled-milled titanium full-arch implant-supported frameworks.
AB  - PURPOSE: To use a novel approach to measure the amount of vertical marginal gap
      in computer numeric controlled (CNC)-milled titanium frameworks and conventional
      cast frameworks. MATERIALS AND METHODS: Ten cast frameworks were fabricated on
      the mandibular master casts of 10 patients. Then, 10 CNC-milled titanium
      frameworks were fabricated by laser scanning the cast frameworks. The vertical
      marginal gap was measured and analyzed using the Contura-G2 coordinate measuring
      machine and special computer software. RESULTS: The CNC-milled titanium
      frameworks showed an overall reduced mean vertical gap compared with the cast
      frameworks in all five analogs. This difference was highly statistically
      significant in the distal analogs. The largest mean gap in the cast framework was
      recorded in the most distal analogs, and the least amount was in the middle
      analog. CONCLUSIONS: Neither of the two types of frameworks provided a completely
      gap-free superstructure. The CNCmilled titanium frameworks showed a significantly
      smaller vertical marginal gap than the cast frameworks.

PMID- 25390865
TI  - Perception of dental esthetics in different cultures.
AB  - PURPOSE: The purpose of this study was to compare patients' and dentists'
      perception of dental appearance. MATERIALS AND METHODS: Based on internationally
      accepted guidelines about dental esthetics, a questionnaire was developed to
      measure "dental appearance" (QDA). Eleven items defined a QDA score (0 =
      "absolutely dissatisfied" to 100 = "absolutely satisfied"). The QDA was completed
      by 29 patients (21 women, 8 men) before and after a complete oral rehabilitation
      that included restoration of the maxillary anterior teeth. Overall, 94 dentists
      from four countries (Germany, the United Kingdom, China, and Switzerland)
      evaluated the esthetics before and after rehabilitation on a visual analog scale
      (VAS: 0 = "absolutely unesthetic" to 100 = "absolutely esthetic"). RESULTS:
      Patients and dentists of all countries found a significant esthetic improvement
      after treatment (P <= .0001). Significant differences could be found when
      comparing the evaluation of the dentists from the various countries among one
      another and with the patients' self-evaluation (P <= .05). With the exception of
      the professional rating of the initial situation, no gender-related differences
      could be found in any of the test groups. CONCLUSIONS: In daily practice, it
      seems of utmost importance for dentists to incorporate the patients' feedback in
      order to avoid esthetic treatment failures.

PMID- 25390866
TI  - Study of surface topography, roughness, and microleakage after dental preparation
      with different instrumentation.
AB  - PURPOSE: The purpose of this study was to compare the differences in surface
      characteristics and roughness of teeth finished for porcelain veneer laminates
      using different instrumentation and to assess their influence on microleakage.
      MATERIALS AND METHODS: Fifty-six extracted human maxillary central incisors were
      divided randomly into two groups: Group HsR teeth were finished with a high-speed
      handpiece with diamond burs; group SO teeth were finished with a sonic
      oscillating diamond instrument. Porcelain veneers were bonded to 24 teeth in each
      group. Microleakage was measured in the cervical area. Four remaining teeth in
      each group were examined using confocal laser-scanning microscopy and scanning
      electron microscopy. RESULTS: Oscillating instruments produced a rougher dentinal
      surface (Ra values; P = .029) than those finished with high-speed rotary
      technology. CONCLUSIONS: There is less microleakage when bonded restoration edges
      are situated over dentin that has been finished with sonic oscillating
      instrumentation (P = .006).

PMID- 25390867
TI  - Prosthodontic management of maxillectomy patients with dental implants in
      residual zygomatic bone: a preliminary report.
AB  - PURPOSE: This report describes the 3-year follow-up of clinical and radiographic
      evaluation of soft and hard tissue outcomes for dental implants placed in
      residual zygoma in patients with surgical resections. Obturator retention and
      support, together with a questionnaire evaluation of the patients' satisfaction
      before and after insertion of implants, also were carried out. MATERIALS AND
      METHODS: A novel approach to the palatomaxillary reconstruction of eight
      maxillectomy patients (mean age: 40 years) using dental implants inserted into
      the remaining zygomatic bone on the affected side and left unloaded for 3 months
      is described. Ball (O-ring) abutments were used with acrylic resin soft tissue
      conformers after surgical soft tissue thinning above the implants. All patients
      were radiographically evaluated and clinically documented at regular follow-up
      appointments. RESULTS: The 3-year follow-up period showed no implant failures,
      stable peri-implant soft tissue level, and an increase in all of the patients'
      satisfaction with their implant-supported obturators. CONCLUSIONS:
      Osseointegrated implants in residual zygomas are an integral part of oral
      rehabilitation strategies, with minimal cost and complications, for maxillectomy
      patients. This short-term record underscores both the potential of such
      management interventions and the importance of even longer-term clinical outcome
      documentation.

PMID- 25390868
TI  - A clinical comparative study of Cadiax Compact II and intraoral records using wax
      and addition silicone.
AB  - Evaluation of mandibular movements is necessary to form the occlusal anatomical
      contour, analyze the temporomandibular joint status, and evaluate the patient's
      occlusion. This clinical study was conducted to compare the mandibular recording
      device Cadiax Compact II with routine intraoral records for measuring condylar
      inclinations. The results showed that the differences between Cadiax and
      intraoral records were statistically significant for all measurements. Cadiax
      measurements had a stronger correlation with silicone records. The quantities of
      recorded Bennett angles were lower and the values of sagittal condylar
      inclination were higher with Cadiax than with routine intraoral records. 

PMID- 25390869
TI  - Technical complications and failures of zirconia-based prostheses supported by
      implants followed up to 7 years: a case series.
AB  - PURPOSE: To evaluate technical complications and failures of zirconia-based fixed
      prostheses supported by implants. MATERIALS AND METHODS: Consecutive patients
      received zirconia-based single crowns (SCs) and fixed dental prostheses (FDPs) on
      implants in a private clinical setting between 2005 and 2010. One dentist
      performed all surgical and prosthetic procedures, and one master technician
      performed and coordinated all laboratory procedures. One-piece computer-aided
      design/ computer-assisted manufacture technology was used to fabricate abutments
      and frameworks, which were directly connected at the implant level, where
      possible. All patients were involved in a recall maintenance program and were
      finally reviewed in 2012. Data on framework fractures, chipping of veneering
      ceramics, and other technical complications were recorded. The primary endpoint
      was failure of the prostheses, ie, the need for a complete remake. A life table
      analysis was calculated. RESULTS: A total of 289 implants supported 193 zirconia
      based prostheses (120 SCs and 73 FDPs) in 127 patients (51 men, 76 women; average
      age: 62.5 +/- 13.4 years) who were reviewed in 2012. Twenty-five (13%) prostheses
      were cemented on 44 zirconia abutments and 168 (87%) prostheses were screw
      retained directly at the implant level. Fracture of 3 frameworks (1 SC, 2 FDPs)
      was recorded, and significant chipping resulted in the remake of 3 prostheses (1
      SC, 2 FDPs). The 7-year cumulative survival rate was 96.4% +/- 1.99%. Minor
      complications comprised 5 loose screws (these were retightened), small chips
      associated with 3 prostheses (these were polished), and dislodgement of 3
      prostheses (these were recemented). Overall, 176 prostheses remained free of
      technical problems. CONCLUSIONS: Zirconia-based prostheses screwed directly to
      implants are clinically successful in the short and medium term.

PMID- 25390870
TI  - Immediate versus early loading of mini-implants supporting mandibular
      overdentures: a preliminary 3-year clinical outcome report.
AB  - PURPOSE: The aim of this preliminary clinical report was to evaluate and compare
      the clinical outcomes of immediate and early loaded mini-implants (MIs)
      supporting mandibular overdentures. MATERIALS AND METHODS: Thirty-six completely
      edentulous patients (20 men and 16 women) complaining of insufficient retention
      of their mandibular dentures were randomly assigned to two groups. Each patient
      received four MIs in the interforaminal area of the mandible using the
      nonsubmerged flapless surgical approach. In group 1 (G1), MIs were loaded with
      mandibular overdentures using the immediate loading protocol, while in group 2
      (G2), MIs were loaded with overdentures using the early loading protocol. The
      cumulative survival rate was calculated using Kaplan-Meier analysis. Peri-implant
      health indices (Plaque Index/Bleeding Index), probing depths, and marginal bone
      levels were recorded for both groups after MI insertions and 6, 12, 24, and 36
      months thereafter. RESULTS: The cumulative implant survival rates were 91.7% and
      96.7% for G1 and G2, respectively. G1 recorded significantly higher Plaque Index,
      Bleeding Index, and probing depths than G2 after 12 months, while other
      observation times demonstrated no significant difference between groups. Most of
      the recorded marginal bone loss occurred in the first year, and no significant
      bone loss was noted in subsequent years. After 6 months, marginal bone loss was
      significantly higher in G1 compared to G2, but no significant differences between
      groups were noted thereafter. CONCLUSIONS: Within the limitations of this study's
      research design and duration of follow-up outcome analyses, immediate and early
      loading protocols showed good clinical results with favorable peri-implant tissue
      response 3 years after implant insertion. Early loading of MIs supporting a
      mandibular overdenture appears to be preferable to immediate loading.

PMID- 25390871
TI  - Effect of an acrylic resin-based resilient liner applied to mandibular complete
      dentures on satisfaction ratings among edentulous patients.
AB  - PURPOSE: The aim of this study was to investigate whether an acrylic resin-based
      resilient liner (ARL) could improve the satisfaction ratings of complete denture
      wearers. The null hypothesis was that no difference exists between the
      satisfaction ratings of conventional acrylic resin denture (CARD) wearers and
      those of ARL denture (ARLD) wearers. MATERIALS AND METHODS: From April 2004 to
      July 2006, a randomized controlled trial was conducted at two centers, including
      74 edentulous patients. Of these, 37 patients were each randomly allocated to the
      ARLD and CARD groups. All of the patients rated their satisfaction with dentures,
      including general satisfaction and satisfaction with chewing ability, speaking,
      cleaning, stability, retention, comfort, and esthetics. These satisfaction
      ratings were measured by a 100-mm visual analog scale. Perceived chewing ability
      of different foods, divided into five grades, was measured using a questionnaire.
      The mastication index (MI) was calculated for each grade. RESULTS: General
      satisfaction, satisfaction with chewing, and satisfaction with speaking were
      significantly higher in the ARLD than in the CARD group (P = .049, .025, and
      .049, respectively). The chewing satisfaction with maxillary dentures in the ARLD
      group was significantly higher than that of the CARD group (P = .02). No
      significant difference existed between the MI of the ARLD (69.2 +/- 17.0) and
      CARD groups (66.7 +/- 18.7). CONCLUSIONS: Within its limitations, this study
      showed that the ARL improves a complete denture wearer's satisfaction ratings.

PMID- 25390872
TI  - Surface porosity of stone casts resulting from immersion of addition silicone
      rubber impressions in disinfectant solutions.
AB  - This study investigated the effects of immersion of addition silicone rubber
      impressions in disinfectant solutions on the surface porosity of the resulting
      stone casts. Five brands of type 2 and 3 addition silicone rubber impression
      materials and one brand of type 4 dental stone were used. Impressions of a master
      die designed to simulate an abutment tooth were immersed in disinfectant for 30
      minutes. The disinfectants used were 2% glutaraldehyde solution and 0.55% ortho
      phthalaldehyde solution. The surface porosities of stone casts obtained from two
      brands of impression materials immersed in disinfectant for 30 minutes were
      determined. Results suggest that impression materials immersed in disinfectant
      solutions need sufficient time before pouring into dental stone. 

PMID- 25390873
TI  - Using acrylic resin tooth veneers in patients with an abnormal jaw relationship:
      a case report.
AB  - This case report describes and evaluates a method of arranging artificial teeth
      in patients with an abnormal jaw relationship in which a wider maxillary arch
      opposes a narrower mandibular arch. First, the fossa of mandibular posterior
      teeth was positioned on the crest of the mandibular edentulous ridge. The
      maxillary posterior teeth were then placed palatally to maximize occlusal
      contacts with the opposing mandibular teeth. Finally, acrylic resin tooth veneers
      were attached on the buccal surface of posterior maxillary teeth to improve the
      arch discrepancy. This method addresses functional considerations with the inner
      aspect of teeth and esthetic considerations with acrylic resin tooth veneers. 

PMID- 25390874
TI  - The association of clinical and microbiologic parameters with histologic
      observations in relatively healthy peri-implant conditions- a preliminary short
      term in vivo study.
AB  - PURPOSE: To determine whether clinical findings-bleeding on probing, pocket
      depth, recession, and bacterial sampling-correlate with histologic outcomes in
      relatively healthy peri-implant soft tissues in people. MATERIALS AND METHODS: In
      this cross-sectional study, a convenience sample of 20 edentulous subjects
      received two endosseous mandibular implants each. The abutments were either
      zirconia (ZrO2) or titanium (Ti) (nonsubmerged implant placement, within-subject
      comparison, leftright randomization). Sulcular bacterial sampling and assessment
      of probing pocket depth, recession, and bleeding on probing were performed 3
      months postsurgery. Mucosal biopsy specimens were obtained, and the blood vessel
      density and a score on an inflammation grading scale were determined. RESULTS:
      Simple linear and linear regression models revealed that the clinical or
      microbiologic parameters were not associated with either of the histologic
      parameters. The soft tissues impressed as healthy, regardless of the abutment
      material. CONCLUSIONS: The peri-implant mucosa around ZrO2and Ti abutments was
      considered healthy in most situations when examined histologically after 3 months
      but showed variation in clinical and microbiologic parameters.

PMID- 25390875
TI  - A new technique for retaining double crowns on implants via custom-positioned
      vertical screws.
AB  - This report describes the use of custom-positioned vertical screws (CVS) to
      attach primary telescopic crowns to implant abutments. In a private practice
      setting, 37 patients with 40 double crown-retained implant overdentures (IODs)
      with a clearance fit (Marburg double crowns) were followed. All primary crowns on
      the 120 implant abutments were retained using CVS. After a mean followup period
      of 3.55 +/- 1.37 years (range: 1.5 to 6.3 years), one abutment screwloosening
      incident was reported (incidence: 0.08%). No loosening of any of the screw
      retained primary crowns occurred. CVS may represent a viable fixation concept for
      IODs. 

PMID- 25390876
TI  - Theoretical role of adjunctive implant positional support in stress distribution
      of distal-extension mandibular removable partial dentures.
AB  - This preliminary study evaluated the adjunctive supporting role of diverse
      implant positions on stress distribution in a Class I removable partial denture
      (RPD) design. Nine three-dimensional finite element models were prepared to
      simulate mandibular RPD designs with three different loading conditions applied.
      Implant supported designs demonstrated lower stress value concentrations and
      mucosal displacement.

PMID- 25390877
TI  - Competition of C(sp2)-X...O halogen bonding and lone pair...pi interactions:
      cryospectroscopic study of the complexes of C2F3X (X = F, Cl, Br, and I) and
      dimethyl ether.
AB  - Inspection of the electrostatic potential of C2F3X (X = F, Cl, Br, and I)
      revealed a second electropositive region in the immediate vicinity of the C?C
      double bond apart from the sigma hole of chlorine, bromine, and iodine, leading
      to C(sp(2))-X...Y halogen bonding, through which complexes stabilized by so
      called lone pair...pi interactions can be formed. Consequently, the experimental
      studies for the complexes of dimethyl ether with C2F3X (X = F, Cl, Br, and I) not
      only allowed one to experimentally characterize and rationalize the effects of
      hybridization on halogen bonding but, for the first time, also allowed the
      competition of C-X...Y halogen bonding and lone pair...pi interactions to be
      studied at thermodynamic equilibrium. Analysis of the infrared and Raman spectra
      reveals that in the cryosolutions of dimethyl ether and C2F3I, solely the halogen
      bonded complex is present, whereas C2F3Br and C2F3Cl give rise to a lone
      pair...pi bonded complex as well as a halogen-bonded complex. Mixtures of
      dimethyl ether with C2F4 solely yield a lone pair...pi bonded complex. The
      experimentally derived complexation enthalpies for the halogen bonded complexes
      are found to be -14.2(5) kJ mol(-1) for C2F3I.DME and -9.3(5) kJ mol(-1) for
      C2F3Br.DME. For the complexes of C2F3Cl with dimethyl ether, no experimental
      complexation enthalpy could be obtained, whereas the C2F4.DME complex has a
      complexation enthalpy of -5.5(3) kJ mol(-1). The observed trends have been
      rationalized with the aid of an interaction energy decomposition analysis (EDA)
      coupled to a Natural Orbital for Chemical Valence (NOCV) analysis and also using
      the noncovalent interaction index method. 

PMID- 25390878
TI  - [Poverty and Health: The Living Standard Approach as a Supplementary Concept to
      Measure Relative Poverty. Results from the German Socio-Economic Panel (GSOEP
      2011)].
AB  - BACKGROUND: A common indicator of the measurement of relative poverty is the
      disposable income of a household. Current research introduces the living standard
      approach as an alternative concept for describing and measuring relative poverty.
      This study compares both approaches with regard to subjective health status of
      the German population, and provides theoretical implications for the utilisation
      of the income and living standard approach in health research. METHODS: Analyses
      are based on the German Socio-Economic Panel (GSOEP) from the year 2011 that
      includes 12 290 private households and 21106 survey members. Self-rated health
      was based on a subjective assessment of general health status. Income poverty is
      based on the equalised disposable income and is applied to a threshold of 60% of
      the median-based average income. A person will be denoted as deprived (inadequate
      living standard) if 3 or more out of 11 living standard items are lacking due to
      financial reasons. To calculate the discriminate power of both poverty
      indicators, descriptive analyses and stepwise logistic regression models were
      applied separately for men and women adjusted for age, residence, nationality,
      educational level, occupational status and marital status. RESULTS: The results
      of the stepwise regression revealed a stronger poverty-health relationship for
      the living standard indicator. After adjusting for all control variables and the
      respective poverty indicator, income poverty was statistically not significantly
      associated with a poor subjective health status among men (OR Men: 1.33; 95% CI:
      1.00-1.77) and women (OR Women: 0.98; 95% CI: 0.78-1.22). In contrast, the
      association between deprivation and subjective health status was statistically
      significant for men (OR Men: 2.00; 95% CI: 1.57-2.52) and women (OR Women: 2.11;
      95% CI: 1.76-2.64). CONCLUSIONS: The results of the present study indicate that
      the income and standard of living approach measure different dimensions of
      poverty. In comparison to the income approach, the living standard approach
      measures stronger shortages of wealth and is relatively robust towards gender
      differences. This study expands the current debate about complementary research
      on the association between poverty and health.

PMID- 25390879
TI  - Subareolar nodule with calcifications on screening mammography.

PMID- 25390881
TI  - A new 3-dimensional dynamic quantitative analysis system of facial motion: an
      establishment and reliability test.
AB  - This study aimed to establish a 3-dimensional dynamic quantitative facial motion
      analysis system, and then determine its accuracy and test-retest reliability. The
      system could automatically reconstruct the motion of the observational points.
      Standardized T-shaped rod and L-shaped rods were used to evaluate the static and
      dynamic accuracy of the system. Nineteen healthy volunteers were recruited to
      test the reliability of the system. The average static distance error measurement
      was 0.19 mm, and the average angular error was 0.29 degrees . The measuring
      results decreased with the increase of distance between the cameras and objects,
      80 cm of which was considered to be optimal. It took only 58 seconds to perform
      the full facial measurement process. The average intra-class correlation
      coefficient for distance measurement and angular measurement was 0.973 and 0.794
      respectively. The results demonstrated that we successfully established a
      practical 3-dimensional dynamic quantitative analysis system that is accurate and
      reliable enough to meet both clinical and research needs. 

PMID- 25390880
TI  - Morphological diversity and polymorphism of self-assembling collagen peptides
      controlled by length of hydrophobic domains.
AB  - Synthetic collagen mimetic peptides are used to probe the role of hydrophobic
      forces in mediating protein self-assembly. Higher order association is an
      integral property of natural collagens, which assemble into fibers and meshes
      that comprise the extracellular matrix of connective tissues. The unique triple
      helix fold fully exposes two-thirds of positions in the protein to solvent,
      providing ample opportunities for engineering interaction sites. Inclusion of
      just a few hydrophobic groups in a minimal peptide promotes a rich variety of
      self-assembly behaviors, resulting in hundred-nanometer to micron size nanodiscs
      and nanofibers. Morphology depends primarily on the length of hydrophobic
      domains. Peptide discs contain lipophilic domains capable of sequestering small
      hydrophobic dyes. Combining multiple peptide types result in composite structures
      of discs and fibers ranging from stars to plates-on-a-string. These systems
      provide valuable tools to shed insight into the fundamental principles underlying
      hydrophobicity-driven higher order protein association that will facilitate the
      design of self-assembling systems in biomaterials and nanomedical applications. 

PMID- 25390882
TI  - Comparison of an Electronic and Paper-based Montreal Cognitive Assessment Tool.
AB  - This pilot study compared a novel electronic Montreal Cognitive Assessment
      (eMoCA) tool to the original paper-based MoCA. Potential participants were
      approached at primary care practices, a geriatric day hospital, and a university
      campus. Each of the 401 participants were randomly assigned to either the eMoCA
      (N=182) or MoCA (N=219). Scores were adjusted by self-reported demographic and
      health information using regression analysis. The difference in average scores
      (26.21+/-3.11 for the MoCA group and 24.84+/-4.21 for the eMoCA group) was found
      to be statistically significant. Controlling for the effect of potential
      covariate factors with regression analyses, the adjusted difference is -0.90 (95%
      confidence interval, -1.45 to -0.35). This difference may be due to factors
      related to use of the electronic device or software usability. However, the
      standardized, self-administered eMoCA may offer an opportunity for health systems
      to screen for early changes in cognitive function in primary care settings and
      offer greater access to assessment for rural or remote communities. Population
      level research may be required to identify whether the score difference between
      test versions requires a downward adjustment to the eMoCA score taken as
      indicative of cognitive impairment. 

PMID- 25390883
TI  - Evaluation of a Brief Survey Instrument for Assessing Subtle Differences in
      Cognitive Function Among Older Adults.
AB  - Most measures of cognitive function used in large-scale surveys of older adults
      have limited ability to detect subtle differences across cognitive domains, and
      standard clinical instruments are impractical to administer in general surveys.
      The Montreal Cognitive Assessment (MoCA) can address this need, but has
      limitations in a survey context. Therefore, we developed a survey adaptation of
      the MoCA, called the MoCA-SA, and describe its psychometric properties in a large
      national survey. Using a pretest sample of older adults (n=120), we reduced MoCA
      administration time by 26%, developed a model to accurately estimate full MoCA
      scores from the MoCA-SA, and tested the model in an independent clinical sample
      (n=93). The validated 18-item MoCA-SA was then administered to community-dwelling
      adults aged 62 to 91 as part of the National Social life Health and Aging Project
      Wave 2 sample (n=3196). In National Social life Health and Aging Project Wave 2,
      the MoCA-SA had good internal reliability (Cronbach alpha=0.76). Using item
      response models, survey-adapted items captured a broad range of cognitive
      abilities and functioned similarly across sex, education, and ethnic groups.
      Results demonstrate that the MoCA-SA can be administered reliably in a survey
      setting while preserving sensitivity to a broad range of cognitive abilities and
      similar performance across demographic subgroups. 

PMID- 25390884
TI  - Clinicopathologic and Genetic Studies of 2 Patients With Hereditary Diffuse
      Leukoencephalopathy With Axonal Spheroids.

PMID- 25390885
TI  - Juvenile hormone enhances aversive learning performance in 2-day old worker honey
      bees while reducing their attraction to queen mandibular pheromone.
AB  - Previous studies have shown that exposing young worker bees (Apis mellifera) to
      queen mandibular pheromone (QMP) reduces their aversive learning performance,
      while enhancing their attraction to QMP. As QMP has been found to reduce the rate
      of juvenile hormone (JH) synthesis in worker bees, we examined whether aversive
      learning in 2-day old workers exposed to QMP from the time of adult emergence
      could be improved by injecting JH (10 ug in a 2 ul volume) into the haemolymph.
      We examined in addition, the effects of JH treatment on worker attraction to QMP,
      and on the levels of expression of amine receptor genes in the antennae, as well
      as in the mushroom bodies of the brain. We found that memory acquisition and 1
      hour memory recall were enhanced by JH. In contrast, JH treatment reduced the
      bees' attraction towards a synthetic strip impregnated with QMP (Bee Boost).
      Levels of expression of the dopamine receptor gene Amdop1 were significantly
      lower in the mushroom bodies of JH-treated bees than in bees treated with vehicle
      alone (acetone diluted with bee ringer). Expression of the octopamine receptor
      gene, Amoa1, in this brain region was also affected by JH treatment, and in the
      antennae, Amoa1 transcript levels were significantly lower in JH-treated bees
      compared to controls. The results of this study suggest that QMP's effects on JH
      synthesis may contribute to reducing aversive learning performance and enhancing
      attraction to QMP in young worker bees. 

PMID- 25390886
TI  - Unstable, metastable, or stable halogen bonding interaction involving negatively
      charged donors? A statistical and computational chemistry study.
AB  - The noncovalent halogen bonding could be attributed to the attraction between the
      positively charged sigma-hole and a nucleophile. Quantum mechanics (QM)
      calculation indicated that the negatively charged organohalogens have no
      positively charged sigma-hole on their molecular surface, leading to a
      postulation of repulsion between negatively charged organohalogens and
      nucleophiles in vacuum. However, PDB survey revealed that 24% of the ligands with
      halogen bonding geometry could be negatively charged. Moreover, 36% of ionizable
      drugs in CMC (Comprehensive Medicinal Chemistry) are possibly negatively charged
      at pH 7.0. QM energy scan showed that the negatively charged halogen bonding is
      probably metastable in vacuum. However, the QM calculated bonding energy turned
      negative in various solvents, suggesting that halogen bonding with negatively
      charged donors should be stable in reality. Indeed, QM/MM calculation on three
      crystal structures with negatively charged ligands revealed that the negatively
      charged halogen bonding was stable. Hence, we concluded that halogen bonding with
      negatively charged donors is unstable or metastable in vacuum but stable in
      protein environment, and possesses similar geometric and energetic
      characteristics as conventional halogen bonding. Therefore, negatively charged
      organohalogens are still effective halogen bonding donors for medicinal chemistry
      and other applications. 

PMID- 25390887
TI  - A mixture of cod and scallop protein reduces adiposity and improves glucose
      tolerance in high-fat fed male C57BL/6J mice.
AB  - Low-protein and high-protein diets regulate energy metabolism in animals and
      humans. To evaluate whether different dietary protein sources modulate energy
      balance when ingested at average levels obesity-prone male C57BL/6J mice were
      pair-fed high-fat diets (67 energy percent fat, 18 energy percent sucrose and 15
      energy percent protein) with either casein, chicken filet or a mixture of cod and
      scallop (1:1 on amino acid content) as protein sources. At equal energy intake,
      casein and cod/scallop fed mice had lower feed efficiency than chicken fed mice,
      which translated into reduced adipose tissue masses after seven weeks of feeding.
      Chicken fed mice had elevated hepatic triglyceride relative to casein and
      cod/scallop fed mice and elevated 4 h fasted plasma cholesterol concentrations
      compared to low-fat and casein fed mice. In casein fed mice the reduced adiposity
      was likely related to the observed three percent lower apparent fat digestibility
      compared to low-fat, chicken and cod/scallop fed mice. After six weeks of feeding
      an oral glucose tolerance test revealed that despite their lean phenotype, casein
      fed mice had reduced glucose tolerance compared to low-fat, chicken and
      cod/scallop fed mice. In a separate set of mice, effects on metabolism were
      evaluated by indirect calorimetry before onset of diet-induced obesity.
      Spontaneous locomotor activity decreased in casein and chicken fed mice when
      shifting from low-fat to high-fat diets, but cod/scallop feeding tended (P =
      0.06) to attenuate this decrease. Moreover, at this shift, energy expenditure
      decreased in all groups, but was decreased to a greater extent in casein fed than
      in cod/scallop fed mice, indicating that protein sources regulated energy
      expenditure differently. In conclusion, protein from different sources modulates
      energy balance in C57BL/6J mice when given at normal levels. Ingestion of a
      cod/scallop-mixture prevented diet-induced obesity compared to intake of chicken
      filet and preserved glucose tolerance compared to casein intake.

PMID- 25390888
TI  - High fidelity system modeling for high quality image reconstruction in clinical
      CT.
AB  - Today, while many researchers focus on the improvement of the regularization term
      in IR algorithms, they pay less concern to the improvement of the fidelity term.
      In this paper, we hypothesize that improving the fidelity term will further
      improve IR image quality in low-dose scanning, which typically causes more noise.
      The purpose of this paper is to systematically test and examine the role of high
      fidelity system models using raw data in the performance of iterative image
      reconstruction approach minimizing energy functional. We first isolated the
      fidelity term and analyzed the importance of using focal spot area modeling,
      flying focal spot location modeling, and active detector area modeling as opposed
      to just flying focal spot motion. We then compared images using different
      permutations of all three factors. Next, we tested the ability of the fidelity
      terms to retain signals upon application of the regularization term with all
      three factors. We then compared the differences between images generated by the
      proposed method and Filtered-Back-Projection. Lastly, we compared images of low
      dose in vivo data using Filtered-Back-Projection, Iterative Reconstruction in
      Image Space, and the proposed method using raw data. The initial comparison of
      difference maps of images constructed showed that the focal spot area model and
      the active detector area model also have significant impacts on the quality of
      images produced. Upon application of the regularization term, images generated
      using all three factors were able to substantially decrease model mismatch error,
      artifacts, and noise. When the images generated by the proposed method were
      tested, conspicuity greatly increased, noise standard deviation decreased by 90%
      in homogeneous regions, and resolution also greatly improved. In conclusion, the
      improvement of the fidelity term to model clinical scanners is essential to
      generating higher quality images in low-dose imaging. 

PMID- 25390890
TI  - Biotransformation of various saccharides and production of exopolymeric
      substances by cloud-borne Bacillus sp. 3B6.
AB  - The ability of Bacillus sp. 3B6, a bacterial strain isolated from cloudwaters, to
      biotransform saccharides present in the atmosphere was evaluated using in situ 1D
      and 2D NMR spectroscopy. Bacillus is one of the genera most frequently described
      in the air and in atmospheric waters. Sugars present in these environments have a
      biogenic origin; they include alditols, monosaccharides, disaccharides,
      oligosaccharides, and polysaccharides. Bacillus sp. 3B6 was able to efficiently
      metabolize sugars, which could thus provide sources of energy for this bacterium
      and allow it to live and to be metabolically active in warm clouds. In addition,
      a number of these saccharides (L-arabitol, D-fructose, sucrose, D-glucose,
      cellotetraose, cellulose, and starch) were transformed to EPSs (exopolymeric
      substances). We have clearly identified the structure of two EPSs as 1,6-alpha
      galactan and partially acetylated polyethylene glycol. 1,6-alpha-Galactan is a
      newly described polymer. The production of EPSs might protect this bacterium
      under hostile cloud environment conditions, including low nutrient availability,
      cold temperature and freeze-thaw processes, UV and radical exposure, and
      evaporation-condensation processes and thus desiccation and osmolarity changes.
      EPSs could also have a potential role in atmospheric processes because they can
      be considered as secondary organic aerosols and efficient cloud condensation
      nuclei.

PMID- 25390889
TI  - The Cytochrome P450 superfamily complement (CYPome) in the annelid Capitella
      teleta.
AB  - The Cytochrome P450 super family (CYP) is responsible for a wide range of
      functions in metazoans, having roles in both exogenous and endogenous substrate
      metabolism. Annelids are known to metabolize polycyclic aromatic hydrocarbons
      (PAHs) and produce estrogen. CYPs are postulated to be key enzymes in these
      processes in annelids. In this study, the CYP complement (CYPome) of the annelid
      Capitella teleta has been robustly identified and annotated with the genome
      assembly available. Phylogenetic analyses were performed to understand the
      evolutionary relationships between CYPs in C. teleta and other species.
      Predictions of which CYPs are potentially involved in both PAH metabolism and
      steroidogensis were made based on phylogeny. Annotation of 84 full length and 12
      partial CYP sequences predicted a total of 96 functional CYPs in C. teleta. A
      further 13 CYP fragments were found but these may be pseudogenes. The C. teleta
      CYPome contained 24 novel CYP families and seven novel CYP subfamilies within
      existing families. A phylogenetic analysis identified that the C. teleta
      sequences were found in 9 of the 11 metazoan CYP clans. Two CYPs, CYP3071A1 and
      CYP3072A1, did not cluster with any metazoan CYP clans. We found xenobiotic
      response elements (XREs) upstream of C. teleta CYPs related to vertebrate CYP1
      (CYP3060A1, CYP3061A1) and from families with reported transcriptional
      upregulation in response to PAH exposure (CYP4, CYP331). C. teleta had a CYP51A1
      with ~65% identity to vertebrate CYP51A1 sequences and has been predicted to have
      lanosterol 14 alpha-demethylase activity. CYP376A1, CYP3068A1, CYP3069A1, and
      CYP3070A1 were the most appropriate candidates for steroidogenesis genes based on
      their phylogeny and warrant further analyses, though no specific aromatase
      (estrogen synthesis) candidates were found. Presence of XREs upstream of C.
      teleta CYPs may indicate a functional aryl hydrocarbon receptor in C. teleta and
      candidate CYPs for studies of PAH metabolism. 

PMID- 25390892
TI  - Summary of BRD data from the 2011 NAHMS feedlot and dairy heifer studies.
AB  - The USDA:APHIS National Animal Health Monitoring System collects data on health
      and health management in livestock and poultry populations throughout the USA in
      order to provide stakeholders with population estimates to use as benchmarks for
      comparison, to guide policy development, and to identify research needs and
      prioritize education efforts. Recent studies of both the beef cattle feedlot
      industry and dairy heifer rearing operations provided information about BRD
      occurrence as well as information about prevention and treatment practices used
      on these operations. While a great deal of effort is dedicated to BRD prevention,
      there are still opportunities to improve the strategies used. Despite efforts to
      prevent the disease, BRD continues to be widespread on both of these types of
      operations. 

PMID- 25390891
TI  - Inhibitors of the interferon response enhance virus replication in vitro.
AB  - Virus replication efficiency is influenced by two conflicting factors, kinetics
      of the cellular interferon (IFN) response and induction of an antiviral state
      versus speed of virus replication and virus-induced inhibition of the IFN
      response. Disablement of a virus's capacity to circumvent the IFN response
      enables both basic research and various practical applications. However, such IFN
      sensitive viruses can be difficult to grow to high-titer in cells that produce
      and respond to IFN. The current default option for growing IFN-sensitive viruses
      is restricted to a limited selection of cell-lines (e.g. Vero cells) that have
      lost their ability to produce IFN. This study demonstrates that supplementing
      tissue-culture medium with an IFN inhibitor provides a simple, effective and
      flexible approach to increase the growth of IFN-sensitive viruses in a cell-line
      of choice. We report that IFN inhibitors targeting components of the IFN response
      (TBK1, IKK2, JAK1) significantly increased virus replication. More specifically,
      the JAK1/2 inhibitor Ruxolitinib enhances the growth of viruses that are
      sensitive to IFN due to (i) loss of function of the viral IFN antagonist (due to
      mutation or species-specific constraints) or (ii) mutations/host cell constraints
      that slow virus spread such that it can be controlled by the IFN response. This
      was demonstrated for a variety of viruses, including, viruses with disabled IFN
      antagonists that represent live-attenuated vaccine candidates (Respiratory
      Syncytial Virus (RSV), Influenza Virus), traditionally attenuated vaccine strains
      (Measles, Mumps) and a slow-growing wild-type virus (RSV). In conclusion,
      supplementing tissue culture-medium with an IFN inhibitor to increase the growth
      of IFN-sensitive viruses in a cell-line of choice represents an approach, which
      is broadly applicable to research investigating the importance of the IFN
      response in controlling virus infections and has utility in a number of practical
      applications including vaccine and oncolytic virus production, virus diagnostics
      and techniques to isolate newly emerging viruses. 

PMID- 25390894
TI  - Structure and properties of neutral and cationic gold(III) complexes from
      substituted 2-(2'-pyridyl)quinoline ligands.
AB  - A one-step catalytic synthesis of 6-substituted 4-phenyl-2-(2'-pyridyl)quinolines
      provides electronically differentiated ligands without solvent, inert atmosphere,
      metal contamination, or chromatography. Gold(III) complexes formed from these
      bidentate PyQuin ligands were characterized and studied by single-crystal X-ray
      diffraction. The cationic gold(III) chloride synthesized from 6-methoxy-4-phenyl
      2-(2'-pyridyl)quinoline has a distorted square-planar ligand environment.
      Diamagnetic neutral gold(III) complexes from methoxy-, methyl-, and phenyl-PyQuin
      ligands exhibit a long axial Au-N2 interaction. 

PMID- 25390893
TI  - Iron overload and apoptosis of HL-1 cardiomyocytes: effects of calcium channel
      blockade.
AB  - BACKGROUND: Iron overload cardiomyopathy that prevails in some forms of
      hemosiderosis is caused by excessive deposition of iron into the heart tissue and
      ensuing damage caused by a raise in labile cell iron. The underlying mechanisms
      of iron uptake into cardiomyocytes in iron overload condition are still under
      investigation. Both L-type calcium channels (LTCC) and T-type calcium channels
      (TTCC) have been proposed to be the main portals of non-transferrinic iron into
      heart cells, but controversies remain. Here, we investigated the roles of LTCC
      and TTCC as mediators of cardiac iron overload and cellular damage by using
      specific Calcium channel blockers as potential suppressors of labile Fe(II) and
      Fe(III) ingress in cultured cardiomyocytes and ensuing apoptosis. METHODS: Fe(II)
      and Fe(III) uptake was assessed by exposing HL-1 cardiomyocytes to iron sources
      and quantitative real-time fluorescence imaging of cytosolic labile iron with the
      fluorescent iron sensor calcein while iron-induced apoptosis was quantitatively
      measured by flow cytometry analysis with Annexin V. The role of calcium channels
      as routes of iron uptake was assessed by cell pretreatment with specific blockers
      of LTCC and TTCC. RESULTS: Iron entered HL-1 cardiomyocytes in a time- and dose
      dependent manner and induced cardiac apoptosis via mitochondria-mediated caspase
      3 dependent pathways. Blockade of LTCC but not of TTCC demonstrably inhibited the
      uptake of ferric but not of ferrous iron. However, neither channel blocker
      conferred cardiomyocytes with protection from iron-induced apoptosis. CONCLUSION:
      Our study implicates LTCC as major mediators of Fe(III) uptake into
      cardiomyocytes exposed to ferric salts but not necessarily as contributors to
      ensuing apoptosis. Thus, to the extent that apoptosis can be considered a
      biological indicator of damage, the etiopathology of cardiosiderotic damage that
      accompanies some forms of hemosiderosis would seem to be unrelated to LTCC or
      TTCC, but rather to other routes of iron ingress present in heart cells.

PMID- 25390895
TI  - Suppression of Cpn10 increases mitochondrial fission and dysfunction in
      neuroblastoma cells.
AB  - To date, several regulatory proteins involved in mitochondrial dynamics have been
      identified. However, the precise mechanism coordinating these complex processes
      remains unclear. Mitochondrial chaperones regulate mitochondrial function and
      structure. Chaperonin 10 (Cpn10) interacts with heat shock protein 60 (HSP60) and
      functions as a co-chaperone. In this study, we found that down-regulation of
      Cpn10 highly promoted mitochondrial fragmentation in SK-N-MC and SH-SY5Y
      neuroblastoma cells. Both genetic and chemical inhibition of Drp1 suppressed the
      mitochondrial fragmentation induced by Cpn10 reduction. Reactive oxygen species
      (ROS) generation in 3-NP-treated cells was markedly enhanced by Cpn10 knock down.
      Depletion of Cpn10 synergistically increased cell death in response to 3-NP
      treatment. Furthermore, inhibition of Drp1 recovered Cpn10-mediated mitochondrial
      dysfunction in 3-NP-treated cells. Moreover, an ROS scavenger suppressed cell
      death mediated by Cpn10 knockdown in 3-NP-treated cells. Taken together, these
      results showed that down-regulation of Cpn10 increased mitochondrial
      fragmentation and potentiated 3-NP-mediated mitochondrial dysfunction in
      neuroblastoma cells. 

PMID- 25390896
TI  - Are subject-specific musculoskeletal models robust to the uncertainties in
      parameter identification?
AB  - Subject-specific musculoskeletal modeling can be applied to study musculoskeletal
      disorders, allowing inclusion of personalized anatomy and properties. Independent
      of the tools used for model creation, there are unavoidable uncertainties
      associated with parameter identification, whose effect on model predictions is
      still not fully understood. The aim of the present study was to analyze the
      sensitivity of subject-specific model predictions (i.e., joint angles, joint
      moments, muscle and joint contact forces) during walking to the uncertainties in
      the identification of body landmark positions, maximum muscle tension and
      musculotendon geometry. To this aim, we created an MRI-based musculoskeletal
      model of the lower limbs, defined as a 7-segment, 10-degree-of-freedom
      articulated linkage, actuated by 84 musculotendon units. We then performed a
      Monte-Carlo probabilistic analysis perturbing model parameters according to their
      uncertainty, and solving a typical inverse dynamics and static optimization
      problem using 500 models that included the different sets of perturbed variable
      values. Model creation and gait simulations were performed by using freely
      available software that we developed to standardize the process of model
      creation, integrate with OpenSim and create probabilistic simulations of
      movement. The uncertainties in input variables had a moderate effect on model
      predictions, as muscle and joint contact forces showed maximum standard deviation
      of 0.3 times body-weight and maximum range of 2.1 times body-weight. In addition,
      the output variables significantly correlated with few input variables (up to 7
      out of 312) across the gait cycle, including the geometry definition of larger
      muscles and the maximum muscle tension in limited gait portions. Although we
      found subject-specific models not markedly sensitive to parameter identification,
      researchers should be aware of the model precision in relation to the intended
      application. In fact, force predictions could be affected by an uncertainty in
      the same order of magnitude of its value, although this condition has low
      probability to occur. 

PMID- 25390897
TI  - Role of recurrent hypoxia-ischemia in preterm white matter injury severity.
AB  - OBJECTIVE: Although the spectrum of white matter injury (WMI) in preterm infants
      is shifting from cystic necrotic lesions to milder forms, the factors that
      contribute to this changing spectrum are unclear. We hypothesized that recurrent
      hypoxia-ischemia (rHI) will exacerbate the spectrum of WMI defined by markers of
      inflammation and molecules related to the extracellular matrix (hyaluronan (HA)
      and the PH20 hyaluronidase) that regulate maturation of the oligodendrocyte (OL)
      lineage after WMI. METHODS: We employed a preterm fetal sheep model of in utero
      moderate hypoxemia and global severe but not complete cerebral ischemia that
      reproduces the spectrum of human WMI. The response to rHI was compared against
      corresponding early or later single episodes of HI. An ordinal rating scale of
      WMI was compared against an unbiased quantitative image analysis protocol that
      provided continuous histo-pathological outcome measures for astrogliosis and
      microglial activation. Late oligodendrocyte progenitors (preOLs) were quantified
      by stereology. Analysis of hyaluronan and the hyaluronidase PH20 defined the
      progressive response of the extracellular matrix to WMI. RESULTS: rHI resulted in
      a more severe spectrum of WMI with a greater burden of necrosis, but an expanded
      population of preOLs that displayed reduced susceptibility to cell death. WMI
      from single episodes of HI or rHI was accompanied by elevated HA levels and
      increased labeling for PH20. Expression of PH20 in fetal ovine WMI was confirmed
      by RT-PCR and RNA-sequencing. CONCLUSIONS: rHI is associated with an increased
      risk for more severe WMI with necrosis, but reduced risk for preOL degeneration
      compared to single episodes of HI. Expansion of the preOL pool may be linked to
      elevated hyaluronan and PH20.

PMID- 25390898
TI  - The status of vitamin B12 and folate among Chinese women: a population-based
      cross-sectional study in northwest China.
AB  - OBJECTIVE: To assess the status of the vitamin B12 and folate of Chinese women
      living in northwest China. METHODS: A population-based cross-sectional study was
      conducted in 2008 among Chinese women aged 10-49 years living in Shaanxi province
      of northwest China. A stratified multistage random sampling method was adopted to
      obtain a sample of 1170 women. The women were interviewed for collection of their
      background information and their plasma vitamin B12 and folate were measured with
      the immunoassay method. The status of both vitamins was evaluated and the
      prevalence of deficiency was estimated. RESULTS: The median value of the women
      was 214.5 pg/mL for vitamin B12 and 4.6 ng/mL for folate. The urban women had a
      significantly higher vitamin B12 (254.1 vs. 195.9 pg/mL) but lower folate (4.4
      vs. 4.7 ng/mL) than rural women. Total prevalence of deficiency was 45.5% (95%
      CI: 42.6% ~ 48.4%) for vitamin B12 and 14.7% (95% CI: 12.6% ~ 16.8%) for folate.
      About 36% of women presented vitamin B12 deficiency alone, 5.2% belonged to
      folate deficiency alone and 9.5% was combined deficiency in both vitamins. More
      than 25% of the women were in marginal vitamin B12 status (200-299 pg/mL) and 60%
      in marginal status of folate (3-6 ng/mL). About 75.2% of rural women with folate
      deficiency were deficient in vitamin B12 and 46% for urban women. Quantile
      regression model found decreasing coefficient of folate status across 73
      different quantiles of vitamin B12, which indicated that the women with folate
      deficiency had lower vitamin B12 significantly compared with those with no
      deficiency. CONCLUSIONS: The deficiency of vitamin B12 and folate is still
      prevalent among the Chinese women in northwest China. Vitamin B12 deficiency
      could be more serious and the improvement of poor vitamin B12 status should be
      invoked when practicing the supplementation of folate against the neural tube
      defects in northwest China.

PMID- 25390900
TI  - Treatment of retinitis pigmentosa-related cystoid macular edema with
      intravitreous ranibizumab.
AB  - PURPOSE: To report the results of the use of intravitreous ranibizumab for
      treatment of cystoid macular edema (CME) associated with retinitis pigmentosa
      (RP). METHODS: Intravitreous ranibizumab was used to treat a patient with CME
      associated with RP who was unable to tolerate oral acetazolamide and did not
      respond to topical dorzolamide treatment. Visual acuity, clinical examination,
      and optical coherence tomography (OCT) were performed before and after treatment.
      RESULTS: Intravitreous ranibizumab improved best-corrected visual acuity (BCVA)
      and decreased central retinal thickness (CRT) with disappearance of cystic spaces
      on the OCT. There was recurrence of CME on discontinuation of injections.
      CONCLUSION: Intravitreous ranibizumab may be an effective therapy for reducing RP
      related CME. Further studies are required to determine whether intravitreous
      ranibizumab is beneficial in the management of this disease.

PMID- 25390901
TI  - Injection site ischemia and inflammation after intravitreal bevacizumab.
AB  - BACKGROUND: Bevacizumab is a monoclonal antibody to vascular endothelial growth
      factor (VEGF) used in the treatment of a variety of ocular conditions. It is
      known to exert an inhibitory effect on new vessels but has not previously been
      documented to affect mature vascular beds. METHODS: The authors present an
      uncommon side effect of intravitreal bevacizumab, consisting of inflammation and
      transient nonperfusion of conjunctival, episcleral, and scleral vessels
      surrounding the injection site. RESULTS: Possible mechanisms of this
      complication, including ischemia and inflammation, are considered. CONCLUSION:
      The possibility of this complication should be recognized by clinicians treating
      patients with intravitreal bevacizumab, and measures should be taken to limit
      drug reflux at the injection site.

PMID- 25390899
TI  - Somatic mutations favorable to patient survival are predominant in ovarian
      carcinomas.
AB  - Somatic mutation accumulation is a major cause of abnormal cell growth. However,
      some mutations in cancer cells may be deleterious to the survival and
      proliferation of the cancer cells, thus offering a protective effect to the
      patients. We investigated this hypothesis via a unique analysis of the clinical
      and somatic mutation datasets of ovarian carcinomas published by the Cancer
      Genome Atlas. We defined and screened 562 macro mutation signatures (MMSs) for
      their associations with the overall survival of 320 ovarian cancer patients. Each
      MMS measures the number of mutations present on the member genes (except for
      TP53) covered by a specific Gene Ontology (GO) term in each tumor. We found that
      somatic mutations favorable to the patient survival are predominant in ovarian
      carcinomas compared to those indicating poor clinical outcomes. Specially, we
      identified 19 (3) predictive MMSs that are, usually by a nonlinear dose-dependent
      effect, associated with good (poor) patient survival. The false discovery rate
      for the 19 "positive" predictors is at the level of 0.15. The GO terms
      corresponding to these MMSs include "lysosomal membrane" and "response to
      hypoxia", each of which is relevant to the progression and therapy of cancer.
      Using these MMSs as features, we established a classification tree model which
      can effectively partition the training samples into three prognosis groups
      regarding the survival time. We validated this model on an independent dataset of
      the same disease (Log-rank p-value < 2.3 * 10(-4)) and a dataset of breast cancer
      (Log-rank p-value < 9.3 * 10(-3)). We compared the GO terms corresponding to
      these MMSs and those enriched with expression-based predictive genes. The
      analysis showed that the GO term pairs with large similarity are mainly pertinent
      to the proteins located on the cell organelles responsible for material transport
      and waste disposal, suggesting the crucial role of these proteins in cancer
      mortality.

PMID- 25390902
TI  - Systemic bevacizumab leads to resolution of diabetic macular edema.
AB  - PURPOSE: The purpose of this study is to report a case of diabetic macular edema
      that resolved after systemic bevacizumab. METHODS: This is an observational case
      report of a patient with diabetic macular edema. RESULTS: After initiation of
      systemic bevacizumab for a central nervous system glioblastoma, the diabetic
      macular edema resolved. CONCLUSION: Systemic bevacizumab may result in the
      resolution of macular edema secondary to diabetes.

PMID- 25390903
TI  - Effect of intravitreal bevacizumab on intraocular pressure in a case of severe
      chronic hypotony.
AB  - PURPOSE: Chronic severe hypotony is associated with many serious ocular
      consequences, including phthisis. This case illustrates a possible new therapy
      for chronic hypotony. METHODS: This study is a case report of a 75-year-old man
      who had undergone trabeculectomy followed by multiple retinal surgeries and
      developed chronic hypotony in the left eye for more than 1 year. RESULTS:
      Treatment with intravitreal bevacizumab led to an elevation of intraocular
      pressure to 8 mmHg 1 week later. Hypotony returned within 2 weeks (2 mmHg) and
      variably remained for 2 months (0-10 mmHg) until a repeat injection of
      intravitreal bevacizumab resulted in another elevation in intraocular pressure,
      which was sustained (5-8 mmHg over 2 months). We postulate that antivascular
      endothelial growth factor therapy may influence aqueous production through
      restoration of tight junctions in the nonpigmented ciliary epithelium. Vascular
      endothelial growth factor and antivascular endothelial growth factor therapies
      have been demonstrated to modulate tight junctions in many other tissues in the
      body, including retinal pigment epithelium, ovarian tissue, vascular endothelium,
      liver, and brain vasculature. CONCLUSION: We postulate that antivascular
      endothelial growth factor therapy may play a role in treating hypotony by
      enhancing the function of tight junctions in the ciliary body and restoring
      aqueous production. Further studies are necessary to better clarify the influence
      of antivascular endothelial growth factor on intraocular pressure and aqueous
      production.

PMID- 25390904
TI  - Successful treatment of choroidal neovascularization complicating a choroidal
      osteoma with intravitreal bevacizumab.
AB  - PURPOSE: To report the effect of off-label use of bevacizumab (Avastin) in the
      treatment of choroidal neovascularization associated with a choroidal osteoma.
      METHODS: Interventional case report examining antivascular endothelial growth
      factor therapy used for choroidal neovascularization complicating a choroidal
      osteoma. RESULTS: A 24-year-old man with a choroidal osteoma presented with
      metamorphopsia and decreased vision in his left eye of 20/60. Clinical
      examination, fluorescein angiography, B-scan ultrasonography, and optical
      coherence tomography revealed a well-circumscribed macular choroidal osteoma with
      overlying subretinal hemorrhage and a choroidal neovascular membrane. The patient
      was treated with a series of 3 intravitreal bevacizumab (Avastin) injections
      (1.25 mg/0.05 mL) performed at baseline, 1 month, and 2 months. Treatment
      resulted in resolution of subretinal hemorrhage and fluid with improvement in
      visual acuity to 20/30 at the 5-month follow-up. CONCLUSION: Intravitreal
      bevacizumab seems to be a promising treatment for choroidal neovascularization
      (CNV) associated with choroidal osteomas.

PMID- 25390905
TI  - Relaxing retinectomy for tractional retinal detachment with retinal capillary
      hemangiomas in genotypically confirmed von hippel-lindau disease.
AB  - PURPOSE: To report the outcome of tractional retinal detachment with retinal
      capillary hemangiomas after pars plana vitrectomy (PPV) and relaxing retinectomy
      in genotypically confirmed von Hippel-Lindau disease (VHL). METHODS:
      Interventional case report of a 28-year-old patient with multiple and large
      retinal capillary hemangiomas underwent PPV combined with relaxing retinectomy.
      RESULTS: Over the next several weeks, the retina recovered to reattachment and
      remained this way for 2 years. In excised angiomas, the finding of a missense
      Arg167Trp mutation and immunohistochemistry staining confirmed the diagnosis of
      VHL. CONCLUSION: Patients with tractional retinal detachment with hemangiomas
      secondary to VHL may benefit from PPV with relaxing retinectomy.

PMID- 25390906
TI  - Regression of choroidal neovascularization after vitrectomy for postinjection
      endophthalmitis.
AB  - PURPOSE: To report regression of choroidal neovascularization following
      vitrectomy for endophthalmitis after antivascular endothelial growth factor
      injections. METHODS: Observational case series of two patients with exudative age
      related macular degeneration. RESULTS: Endophthalmitis developed 2 days after the
      fourth ranibizumab injection in 1 case and 1 day after the ninth bevacizumab
      injection in another case. Vitrectomy and intravitreal antibiotic injections were
      performed. There was no bacterial growth on the cultures. Postoperative
      fluorescein angiography and combined optical coherence tomography/scanning laser
      ophthalmoscopy showed regression of choroidal neovascularization that was
      sustained after 29 and 32 months follow-up. CONCLUSION: In both patients with
      active exudative age-related macular degeneration, regression of choroidal new
      vessels occurred after vitrectomy and injection of intravitreal antibiotics for
      the treatment of endophthalmitis. Removal of the posterior vitreous during
      vitrectomy may have eliminated the contribution of vitreous to exudative age
      related macular degeneration and choroidal neovascularization.

PMID- 25390907
TI  - Spectral-domain optical coherence tomography features of hypotonous maculopathy
      after successful retinal detachment surgery.
AB  - PURPOSE: To describe the spectral-domain optical coherence tomography features in
      a patient with an atypical presentation of hypotonous maculopathy after
      successful retinal detachment surgery. METHODS: A 64-year-old man underwent
      scleral buckling with pars plana vitrectomy for the repair of retinal detachment.
      Postoperatively, the retina was attached but he had poor recovery of vision.
      Intraocular pressure was recorded to be on the lower side of normal. He underwent
      posterior segment evaluation by spectral-domain optical coherence tomography.
      RESULTS: Spectral-domain optical coherence tomography revealed cystoid macular
      edema and a neurosensory detachment involving the posterior pole. In addition,
      underneath the neurosensory detachment, spectral-domain optical coherence
      tomography revealed folds of the retinal pigment epithelium and Bruch membrane,
      features of hypotonous maculopathy. CONCLUSION: Spectral-domain optical coherence
      tomography is a useful investigational modality in the diagnosis of ocular
      hypotony presenting with atypical features.

PMID- 25390908
TI  - Neovascular glaucoma as a first clinical manifestation of multiple sclerosis.
AB  - PURPOSE: To report a case with neovascular glaucoma caused by severe occlusive
      retinal vasculitis, as a first clinical manifestation of multiple sclerosis (MS).
      METHODS: Examination on an otherwise healthy 45-year-old man presenting with
      blurred vision in his right eye revealed bilateral iris neovascularization, right
      eye neovascular glaucoma, and bilateral retinal neovascularization caused by
      vasculitis. Thorough systemic investigation indicated by an ophthalmologist
      showed nothing else other than typical to MS imaging and spinal tap findings. The
      patient received bilateral treatment with panretinal photocoagulation and
      intravitreal bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA)
      injection in the right eye. RESULTS: Ten months later, the patient was found with
      paraclinical neurologic findings completing the diagnostic criteria of definite
      laboratory supported MS. After the 3 years that followed, the ocular disease was
      eliminated, and the underlying disease remains clinically silent. CONCLUSION: As
      illustrated by our case, MS should be considered as an underlying disorder in
      patients with neovascular glaucoma caused by occlusive retinal vasculitis.

PMID- 25390909
TI  - Temporal branch retinal vein occlusion secondary to a racemose hemangioma.
AB  - PURPOSE: To describe a case of venous thrombosis secondary to unilateral racemose
      hemangioma (RH). METHODS: Biomicroscopic examination, fluorescein angiography,
      and optical coherence tomography were used. The patient was a 12-year-old girl
      who was seen for progressive loss of visual acuity in the left eye. RESULTS:
      Examination revealed venous thrombosis in the superior temporal vein area in the
      context of arteriovenous malformation (AVM). Treatment with intravitreal
      triamcinolone (4 mg) resulted in anatomic and functional improvement. CONCLUSION:
      This was an exceptional case of branch retinal vein occlusion secondary to RH in
      a girl without known risk factors for venous obstruction. The obstruction was
      attributable to the large-caliber superior temporal artery, which, on forming a
      loop in the region of the venous branch, produced an obstruction of venous branch
      blood flow.

PMID- 25390910
TI  - Posterior scleritis in patients with systemic lupus erythematosus.
AB  - PURPOSE: To describe three cases of posterior scleritis associated with systemic
      lupus erythematosus. METHODS: Retrospective chart review including ophthalmic
      examination, fundus photography, optical coherence tomography, angiography,
      ultrasonography, and/or magnetic resonance imaging. RESULTS: Three patients
      presented with blurred vision, red eye, and/or eye pain in one or both eyes. The
      diagnosis of posterior scleritis was confirmed in each patient using B-scan
      ultrasonography. One patient presented with giant nodular scleritis. In two
      patients, posterior scleritis was the presenting sign of systemic lupus
      erythematosus. Two patients received systemic corticosteroids together with
      noncorticosteroid immunosuppressive medications. One patient received topical and
      periocular injections of corticosteroids. All three patients showed prompt
      resolution of their posterior scleritis in response to treatment. CONCLUSION:
      While uncommon, posterior scleritis may occur in patients with systemic lupus
      erythematosus and, in some instances, may be the presenting sign of the disease.
      Prompt diagnosis and treatment was associated with good visual outcomes in our
      patients.

PMID- 25390911
TI  - Purtscher-like retinopathy with serous retinal detachment in preeclampsia of
      pregnancy: complications and management.
AB  - PURPOSE: We report the management of a young woman with preeclampsia of pregnancy
      who developed bilateral Purtscher-like retinopathy and serous retinal detachment
      subsequently complicated by macular hole and tractional retinal detachment.
      METHODS: The best-corrected visual acuity was 20/1000 bilaterally. Fundus
      examination showed a picture of Purtscher-like retinopathy bilaterally and a
      macular hole in the right eye. Fluorescein angiography showed areas of capillary
      dropout and Elschnig spots bilaterally. Optical coherence tomography confirmed
      the macular hole in the right eye and a shallow serous retinal detachment
      bilaterally. Systemic and laboratory workup was unremarkable. Triamcinolone
      acetonide (4 mg/0.1 mL) was injected intravitreally in the left eye; vitrectomy
      was advised for the right eye. However, when the patient returned after 4 months,
      the right eye had developed a macular tractional retinal detachment. Vitrectomy,
      membrane peeling, and gas tamponade were performed. RESULTS: When the patient
      returned 4 months after the intravitreal injection in the left eye, best
      corrected visual acuity had improved to 20/40 with complete resolution of serous
      retinal detachment in that eye. Best-corrected visual acuity in the right eye
      remained at 20/1000 but with anatomic deterioration. One month after vitrectomy
      for the macular hole and tractional retinal detachment in the right eye, best
      corrected visual acuity improved to 20/240 with normalizing foveal contours.
      Status quo was observed in both eyes for the next 8 months. Final best-corrected
      visual acuity was 20/200 in the right eye and 20/40 in the left eye. CONCLUSION:
      An unusual combination of Purtscher-like retinopathy with serous retinal
      detachment in preeclampsia of pregnancy and its complication-macular hole with
      tractional retinal detachment-were managed by surgery and pharmacotherapy.

PMID- 25390912
TI  - An extensive case of acute posterior multifocal placoid pigment epitheliopathy.
AB  - PURPOSE: To report a case of extensive acute posterior multifocal placoid pigment
      epitheliopathy (APMPPE). METHODS: Case report. RESULTS: An 18-year-old girl was
      admitted and treated with intravenous acyclovir and intravitreal gancyclovir for
      presumed acute retinal necrosis. As the lesions faded and vision improved, the
      findings became more consistent with an extensive form of APMPPE. CONCLUSION:
      Acute posterior multifocal placoid pigment epitheliopathy can present very
      aggressively early in its course. Despite macular involvement, as in this
      patient, vision can improve significantly.

PMID- 25390913
TI  - Photoreceptor attenuation in acute zonal occult outer retinopathy.
AB  - PURPOSE: The purpose of this study is to report a case of acute zonal occult
      outer retinopathy and to describe a novel method of imaging photoreceptor damage
      using Cirrus spectral-domain optical coherence tomography (SD-OCT; Cirrus, Carl
      Zeiss Meditec, Dublin, CA) en face visualization. Our examination also included
      color fundus photographs, Goldmann visual field, fluorescein and indocyanine
      green angiography, fundus autofluo-rescence, and Ganzfeld electroretinography.
      METHODS: This is a case report of a single patient. RESULTS: Despite 20/20 visual
      acuity in both of our patient's eyes, Goldmann visual field showed a unilateral C
      shaped scotoma centered on the left optic nerve, sparing the fovea. Fundus and
      angiographic findings showed nonspecific pigmentary changes and hyperfluo-rescent
      foci along the superior and inferior vascular arcades. The electroretinography
      showed decreased scotopic amplitudes, with impaired 30-Hz flicker response, and
      Cirrus SD-OCT showed loss of the inner segment/outer segment photoreceptor
      junction. Cirrus SD-OCT Advanced Visualization three-dimensional reconstruction
      with en face visualization delineated an area of inner segment/outer segment
      attenuation corresponding to the Goldmann visual field scotoma. The patient's
      condition was unchanged at 5 months follow-up. CONCLUSION: In addition to classic
      diagnostic modalities, photoreceptor attenuation observed with Cirrus SD-OCT can
      contribute to the diagnosis of acute zonal occult outer retinopathy and may help
      elucidate the etiology of this puzzling condition.

PMID- 25390914
TI  - Multifocal juvenile xanthogranuloma presenting with a hand mass and bilateral
      vitreous hemorrhage in a neonate.
AB  - PURPOSE: To describe a rare case of multifocal juvenile xanthogranuloma (JXG) in
      a neonate presenting with a large hand mass, bilateral vitreous hemorrhage, and
      posterior segment involvement. METHODS: Biopsy of hand lesion led to the
      diagnosis of JXG. Further systemic workup and ocular examination revealed
      bilateral vitreous hemorrhage and a small, creamy yellowish subretinal lesion
      above the fovea in the macula of the left eye. In addition, there was a
      subretinal lesion with overlying vitreous fibrosis in the inferonasal quadrant of
      the left eye. RESULTS: Treatment with prednisone (2 mg/kg/day) for 2 weeks was
      initiated before final diagnosis of hand lesion. Steroids were then tapered off
      over the course of a week with no additional treatment. Follow-up examinations
      were performed over the course of the next 17 months. On the last follow-up
      examination at the age of 20 months, the child had central steady and maintained
      fixation in each eye. The findings of an external ocular examination were
      unremarkable except for a mild myopic shift in the right eye secondary to trace
      cataract changes. Dilated fundus examination showed resolution of the lesions in
      the macula and inferonasal quadrant of the left eye. CONCLUSION: Although rare,
      JXG should be included in the differential diagnosis of spontaneous vitreous
      hemorrhage in children under the age of 2 years. Topical, periocular, and oral
      steroids may improve the ocular signs and symptoms in this condition and should
      be considered in the management of ophthalmic manifestations of JXG.

PMID- 25390915
TI  - Comparing different imaging modalities in harada disease: a case report.
AB  - PURPOSE: The purpose of this study was to compare fluorescein angiography,
      infrared imaging, fundus autofluorescence, and optical coherent tomography for
      the diagnosing and monitoring of Harada disease. METHODS: This was an
      interventional case report. RESULTS: A 46-year-old Chinese woman presented with
      headache, tinnitus, and diminished vision in both eyes. Examination revealed
      bilateral exudative retinal detachment. Optical coherence tomography showed fluid
      accumulation in three different layers (intraretinal, subretinal, and subretinal
      pigment epithelium). Fundus autofluorescence revealed regions of
      hypoautofluorescence as a result of the thick fluid accumulation. Infrared
      imaging revealed more clinically relevant information than did fundus
      autofluorescence in this case. CONCLUSION: In Harada disease, excessive fluid
      accumulates in three different layers. Optical coherence tomography is the most
      effective modality in measuring the axial distribution of the fluid in the z
      plane, whereas infrared imaging is better at providing the information in the x-y
      plane, compared with fundus autofluorescence.

PMID- 25390916
TI  - Plasmapheresis in the management of choroidal vasculitis associated with C-anca
      positive renal vasculitis.
AB  - PURPOSE: The purpose of this study was to report the use of plasmapheresis in the
      management of choroidal vasculitis associated with Wegener granulomatosis.
      METHOD: Case report. PATIENT: A 50-year-old woman with acute renal failure as a
      result of glomerulonephritis of the Wegener granulomatosis type presented with
      sudden visual loss. Visual acuities at presentation were counting fingers in the
      left eye and 6/24 in the right eye. Clinical examination showed significant
      choroidal ischemia with no evidence of vitritis or anterior segment inflammation.
      Fluorescein and indocyanine green angiography confirmed choroidal vasculitis.
      RESULTS: The patient was treated with a course of seven plasmapheresis sessions,
      after which she was maintained on prednisolone and mycophenolate. One week after
      her presentation, vision improved to 6/6 bilaterally. The angiographic
      appearances resolved, and the patient was maintained on immunosuppression.
      CONCLUSION: We believe that the prompt use of plasmapheresis prevented
      irreversible visual loss in this patient. This case illustrates the dramatic
      improvement in choroidal perfusion presumably resulting from the removal of a
      circulating immune factor.

PMID- 25390917
TI  - Peripapillary choroidal neovascularization associated with kenny syndrome.
AB  - PURPOSE: To report a case of Kenny-Caffey syndrome with peripapillary choroidal
      neovascularization. METHODS: An observational case report with clinical findings
      demonstrated by wide-field retinal photographic and angiographic evaluation of a
      patient with Kenny-Caffey syndrome. RESULTS: Wide-field retinal photography and
      fluorescein angiography showed characteristic findings seen in Kenny-Caffey
      syndrome (crowded optic nerves, retinal vascular tortuosity). In addition, the
      previously undocumented finding of peripapillary choroidal neovascularization is
      demonstrated. CONCLUSION: The development of peripapillary choroidal
      neovascularization can occur in patients with Kenny-Caffey syndrome. The
      development of this finding may be secondary to abnormalities of the optic nerve
      inherent in this rare disorder.

PMID- 25390918
TI  - Cytomegalovirus acute retinal necrosis in an immunocompetent patient after sub
      tenon triamcinolone injection.
AB  - PURPOSE: To report a case of cytomegalovirus acute retinal necrosis after a sub
      Tenon injection of triamcinolone acetonide in an immunocompetent patient.
      METHODS: A 77-year-old man received a sub-Tenon injection of triamcinolone
      acetonide for treatment of iritis unresponsive to topical steroids. He
      subsequently developed unilateral acute retinal necrosis. RESULTS: Vitreous
      biopsy with polymerase chain reaction analysis was positive for cytomegalovirus.
      Implantation of a sustained-release ganciclovir device resulted in disease
      stabilization. CONCLUSION: Cytomegalovirus can be a causative agent of both
      anterior uveitis and acute retinal necrosis. A potential complication of a sub
      Tenon steroid injection may be viral reactivation causing acute retinal necrosis
      secondary to localized immunosuppression.

PMID- 25390919
TI  - Chronic postoperative fungal endophthalmitis caused by trichosporon asahii.
AB  - PURPOSE: To describe a patient with chronic postoperative fungal endophthalmitis
      caused by Trichosporon asahii. METHODS: A retrospective case report. RESULTS: An
      82-year-old woman was found to have culture-proven T. asahii chronic fungal
      endophthalmitis with initial symptoms beginning 18 months after uneventful
      phacoemulsification with intraocular lens implantation. Successful treatment was
      achieved with pars plana vitrectomy, capsulectomy, and oral voriconazole without
      explantation of the intraocular lens. CONCLUSION: This is the first reported case
      of chronic postoperative T. asahii endophthalmitis. Our patient was successfully
      treated with pars plana vitrectomy, capsulectomy, and oral voriconazole without
      explantation of the intraocular lens.

PMID- 25390920
TI  - Central retinal artery occlusion associated with hypertriglyceridemia.
AB  - PURPOSE: To report a case of central retinal artery occlusion associated with
      hypertriglyceridemia. METHODS: A 46-year-old man presented with decreased vision
      and was found to have a central retinal artery occlusion. Laboratory testing
      demonstrated markedly elevated trig-lycerides with no other abnormalities. Tests
      for cardiac and carotid embolic sources and hypercoagulability were negative.
      RESULTS: Dietary management and medication compliance resulted in dramatically
      decreased serum triglyceride levels. Vision remained poor during follow-up.
      CONCLUSION: Central retinal artery occlusion requires a medical evaluation for
      embolic and thrombotic sources. A fasting lipid panel is inexpensive to obtain
      and should be considered in the workup for central retinal artery occlusion.

PMID- 25390921
TI  - Retinal vascular occlusions and macular thinning in fibromuscular dysplasia.
AB  - PURPOSE: To report retinal findings in a patient with fibromuscular dysplasia.
      METHODS: A retrospective case report. RESULTS: A 36-year-old female patient with
      fibromuscular dysplasia and a history of cerebrovascular events presented with
      painless vision loss in the left eye. Ophthalmologic evaluation demonstrated
      retinal vascular occlusive disease and secondary macular thinning. CONCLUSION:
      This case demonstrates that fibromuscular dysplasia can affect the retinal
      vasculature and lead to macular ischemia and vision loss.

PMID- 25390922
TI  - Cup-shaped choroidal excavation detected by optical coherence tomography: a case
      report.
AB  - PURPOSE: The purpose of this study was to report a case with a cup-shaped
      choroidal excavation in the fovea. This condition was detected only by optical
      coherence tomography (OCT) and seems to be rare. METHOD: This was an
      observational case report. RESULT: A 29-year-old man had a central scotoma in his
      right eye. Color photography showed a reddish lesion in the fovea of the right
      eye, which was shown as a window defect on fluorescein angiography. Tomography
      with time-domain OCT showed a retinal pigment epithelial and choroidal excavation
      corresponding to the reddish macular lesion in the right eye. By using spectral
      domain OCT, the inner segment and outer segment junctions of photoreceptors line
      thickening was detected by tomography, and the retinal pigment epithelium line
      was observed in the area of choroidal excavation by segmentation analysis.
      CONCLUSION: The reddish lesion on ophthalmoscope corresponded to the excavation
      lesion, detected in the fovea only by OCT; this indicates a new clinical
      availability of OCT in clinical diagnosis.

PMID- 25390923
TI  - Intracoital subfoveal hemorrhage after tadalafil (cialis) premedication: a case
      report.
AB  - PURPOSE: The purpose of this study is to report the first case, to our knowledge,
      of intracoital subfoveal hemorrhage occurring 1 hour after tadalafil
      premedication in a patient with previously undiagnosed retinal angiomatous
      proliferation and erectile dysfunction. METHODS: This is an interventional case
      report. The patient underwent Snellen vision acuity measurement, anterior and
      posterior segment biomicroscopy, and indirect ophthalmoscopy. Optical coherence
      tomography, fluorescein angiography, and indocyanine green angiography were also
      performed as needed. Recombinant tissue plasminogen activator 100 MUg/0.1 mL and
      0.3 mL pure SF6 gas were injected in the vitreous on presentation. Four days
      later, the patient received 1.25 mg/0.1 mL of intravitreal bevacizumab. RESULTS:
      One day after recombinant tissue plasminogen activator and gas injection, visual
      acuity rose to 20/60-2. A week later, visual acuity was unchanged, and the
      subretinal hemorrhage displaced from the foveola. Optical coherence tomography
      showed a marked regression of submacular thickening. CONCLUSION: Despite strict
      time correlation, the submacular hemorrhage cannot be unequivocally attributed to
      tadalafil assumption because many other risk factors are to be considered: the
      Valsalva maneuver above all. Nonetheless, a suspicion should be raised, at least
      as a cofactor, given the drug mechanism of action and the report of vascular
      abnormalities bleeding in the literature, including cerebral arterovenous
      malformation and epistaxis. Caution should be exercised in the prescription of
      phosphodiesterase type 5 inhibitors to patients with known vascular abnormalities
      including retinal and choroidal abnormalities: retinal angiomatous proliferation,
      classic and occult neovascularization of any origin, and also, possibly,
      hemangioma.

PMID- 25390924
TI  - Photodynamic therapy in a case of polypoidal choroidal vasculopathy associated
      with choroidal nevus.
AB  - PURPOSE: The purpose of this study was to report the clinical findings and
      management of a case of polypoidal choroidal vasculopathy associated with
      choroidal nevus. METHODS: A 59-year-old woman with a subfoveal vascular network
      with polypoidal lesions associated with choroidal nevus was treated with
      photodynamic therapy. The initial visual acuity was 1/60. Treatment was performed
      according to identical parameters to those used for choroidal neovascularization
      secondary to age-related macular degeneration and was repeated 3 months after the
      first application. The patient was prospectively followed with optical coherence
      tomography, fluorescein angiography, and indocyanine angiography. RESULTS: After
      the second treatment, total occlusion of the polypoidal lesions was observed but
      the vascular network remained still patent. During the 5-year follow-up, no
      recurrence was observed and the visual acuity rose to 1/10. CONCLUSION: In our
      experience, photodynamic therapy had positive results and this indicates the
      possibility that it could be a useful tool to manage these lesions and to improve
      their prognosis.

PMID- 25390925
TI  - Ocular features of the organoid nevus syndrome.
AB  - PURPOSE: The purpose of the study was to demonstrate the ocular features of
      organoid nevus syndrome. METHODS: A 10-day-old male infant was referred for
      management of retinoblastoma as a result of the presence of intraocular
      calcification. The examination showed a cutaneous lesion in the midline,
      epibulbar vascular lesions, and a cutaneous nodule at the lateral canthus. Fundus
      evaluation showed circumpapillary flat discoloration, which appeared hyperdense
      on ultrasound. RESULTS: All these features were consistent with organoid nevus
      syndrome. The cutaneous lesion was consistent with nevus sebaceous, the epibulbar
      lesion with choristoma, and the fundus lesion with cartilaginous choristoma.
      CONCLUSION: The presence of intraocular calcification often leads to a mistaken
      diagnosis in organoid nevus syndrome. Appropriate identification is important to
      diagnose this multisystem disorder.

PMID- 25390926
TI  - Presumed metastasis of choroidal melanoma to the contralateral choroid.
AB  - PURPOSE: To report a case of choroidal melanoma metastasizing to contralateral
      choroid along with systemic metastasis. METHODS: This is a retrospective study of
      a case of a 52-year-old man who was found to have a choroidal lesion in the left
      eye temporal to fovea. The ultrasound and angiographic findings were suggestive
      of choroidal melanoma, which prompted enucleation of the eye. RESULTS: After
      approximately 74 months, the patient noticed decreased vision in the
      contralateral (right) eye. Examination revealed a nonpigmented mass lesion
      approximately two disk diameters in size superotemporal to fovea, and the patient
      was found to have multiple secondary tumors in the abdomen and liver. CONCLUSION:
      The development of choroidal metastases from a contralateral choroidal melanoma
      is of ophthalmic interest and seems to be unique.

PMID- 25390927
TI  - Uveal metastasis from nonsmall cell lung carcinoma with dramatic response to
      erlotinib.
AB  - PURPOSE: To report the case of a never-smoker patient whose initial presentation
      of metastatic nonsmall cell lung carcinoma was with uveal metastasis, which had a
      dramatic response to targeted biologic therapy with erlotinib (Tarceva) after
      failing conventional chemotherapy. METHODS: Case report. A 43-year-old man with
      uveal metastasis from nonsmall cell lung adenocarcinoma. RESULTS: After failing
      conventional chemotherapy with carboplatin and taxol, with continued documented
      rapid growth of the uveal metastasis, treatment was initiated with the targeted
      biologic agent, erlotinib, which is a protein tyrosine kinase inhibitor of the
      epidermal growth factor receptor(EGFR). Within 3 days of starting erlotinib,
      shrinkage of the choroidal lesion was noted, and over the course of the next 3
      months, the tumor completely and durably disappeared, with vision improving from
      hand motion to 20/25. The patient is still alive and well after 3 years, on
      continued daily oral erlotinib treatment. CONCLUSION: Erlotinib is a well
      tolerated newly available Food and Drug Administration-approved oral targeted
      biologic agent, which may be beneficial in some patients with uveal metastasis
      from nonsmall cell lung carcinoma, in which an underlying epidermal growth factor
      receptor mutation is suspected.

PMID- 25390928
TI  - Serous retinal detachment as a presenting feature of chronic myelogenous
      leukemia.
AB  - PURPOSE: The purpose of this study was to report a case of diffuse unilateral
      retinal detachment as an initial symptom of chronic myelogenous leukemia in a 35
      year-old woman. METHODS: This is a case report of a 35-year-old white woman who
      presented with painless acute visual loss in her left eye. RESULTS: A 35-year-old
      white woman presented with acute visual loss in her left eye. She had no systemic
      or ophthalmological medical history. Slit-lamp examination was normal in both
      eyes. Fundus examination of the left eye showed not only multiple retinal
      hemorrhages but also a diffuse serous retinal detachment affecting the nasal
      aspect of the retina and the posterior pole. The leukocyte count was 124,000/mm
      (99% blasts), and the Philadelphia chromosome was positive, an abnormality that
      is associated with chronic myelogenous leukemia. CONCLUSION: Serous retinal
      detachment is an uncommon feature among leukemias. Chronic myelogenous leukemia
      may remain asymptomatic until a blastic phase occurs. Prompt recognition of the
      disease leads to early systemic chemotherapy and may help to restore visual
      function.

PMID- 25390929
TI  - The suboptimal role of optical coherence tomography in diagnosing choroidal
      metastasis in the macula.
AB  - PURPOSE: To describe the clinical, optical coherence tomography, and echographic
      findings of a choroidal metastasis in the macula. An initial, erroneous diagnosis
      of a serous pigment epithelial detachment of the macula had been based on
      ophthalmoscopic and optical coherence tomography findings. METHODS: Case report
      of a patient with blurred vision in one eye and presumed serous pigment
      epithelial detachment. RESULTS: An 83-year-old man with blurred vision and
      presumed serous pigment epithelial detachment was self-referred to our clinic for
      a second opinion. Optical coherence tomography showed an elevation of the
      neurosensory macula, but no abnormalities were reflected from the choroid. We
      performed an ultrasound evaluation, which revealed a solid mass involving the
      macular region of the choroid. The echo-graphic characteristics, including low
      internal reflectivity, regular structure, and vas-cularity, were consistent with
      choroidal melanoma or metastasis from any small cell carcinoma. The patient was
      not aware of any active primary tumor. An extensive systemic workup was
      performed. His prostate-specific antigen was found to be elevated to 61.4 ng/mL,
      and a prostate biopsy was positive for adenocarcinoma. Additional studies
      revealed metastatic disease involving the bones, pulmonary parenchyma, and
      mediastinal and retroperitoneal lymph nodes. CONCLUSION: Ultrasound imaging was
      superior to optical coherence tomography imaging in the clinical setting of a
      choroidal mass in the macula.

PMID- 25390930
TI  - A comparison of self-esteem and perfectionism in anorexia nervosa and body
      dysmorphic disorder.
AB  - Previous studies have identified phenotypic similarities between anorexia nervosa
      (AN) and body dysmorphic disorder (BDD), which share the common feature of
      negative body image. Studies comparing endophenotypes that may cut across both
      disorders-as suggested by the National Institute of Mental Health's Research
      Domain Criteria-are limited. Sixty-nine individuals (AN, n = 24; BDD, n = 23;
      mentally healthy controls [MHCs], n = 22) completed diagnostic interviews and
      self-reports assessing self-esteem and perfectionism. Clinical groups showed
      greater perfectionism in almost all subdimensions as well as poorer self-esteem
      compared with MHCs, with no clinical group differences when controlling for level
      of depression. Depression was a mediator of the relationship between symptom
      severity and self-esteem in both clinical groups. Comparable low self-esteem and
      greater perfectionism in AN and BDD corroborated existing etiological models and
      previous studies. Depression was a significant contributor to negative self
      esteem in both disorders. 

PMID- 25390931
TI  - How do clinicians actually use the Diagnostic and Statistical Manual of Mental
      Disorders in clinical practice and why we need to know more.
AB  - The clinical use of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM) is explicitly stated as a goal for both the DSM Fourth Edition and DSM
      Fifth Edition (DSM-5) revisions. Many uses assume a relatively faithful
      application of the DSM diagnostic definitions. However, studies demonstrate
      significant discrepancies between clinical psychiatric diagnoses with those made
      using structured interviews suggesting that clinicians do not systematically
      apply the diagnostic criteria. The limited information regarding how clinicians
      actually use the DSM raises important questions: a) How can the clinical use be
      improved without first having a baseline assessment? b) How can potentially
      significant shifts in practice patterns based on wording changes be assessed
      without knowing the extent to which the criteria are used as written? Given the
      American Psychiatric Association's plans for interim revisions to the DSM-5, the
      value of a detailed exploration of its actual use in clinical practice remains a
      significant ongoing concern and deserves further study including a number of
      survey and in vivo studies. 

PMID- 25390932
TI  - Matrix-assisted laser desorption ionization: time of flight mass spectrometry
      identified models for detection of ESBL-producing bacterial strains.
AB  - BACKGROUND: The increase in the amount of extended spectrum beta-lactamases
      (ESBL)-producing gram-negative bacteria is seriously threatening human health in
      recent years. Therefore, it is necessary to develop a rapid and reliable method
      for identification of ESBLs. The purpose of this study was to establish a novel
      method to discriminate between ESBL-producing and non- ESBL-producing bacteria by
      using the matrix-assisted laser desorption/ionization time of flight mass
      spectrometry (MALDI-TOF-MS) technique. MATERIAL/METHODS: We detected hydrolyzed
      production of cefotaxime after incubation with 69 gram-negative bacteria by using
      MALDI-TOF-MS. Then we established genetic algorithm (GA), supervised neural
      networks (SNN), and quick classifier (QC) models using several peaks to identify
      ESBL-producing strains. To confirm the clinical applicability of the models
      established, a blinded validation test was performed in 34 clinical isolated
      strains. RESULTS: Using ClinPro Tools software, we identified 4 peaks (456 Da,
      396 Da, 370 Da, and 371 Da) in mass spectra of cefotaxime solution that have high
      enough specificity to discriminate ESBL-producing from non- ESBL-producing
      strains. Recognition capability of models established were 97.5% (GA), 92.5%
      (SNN), and 92.5% (QC), and cross validation rates were 90.15% (GA), 97.62 (SNN),
      and 97.62% (QC). The accuracy rates of the blinded validation test were 82.4%
      (GA), 88.2% (SNN), and 82.4% (QC). CONCLUSIONS: Our results demonstrate that
      identification of ESBLs strains by MALDI-TOF-MS has potential clinical value and
      could be widely used in the future as a routine test in clinical microbiology
      laboratories.

PMID- 25390933
TI  - A linkage between SmeIJK efflux pump, cell envelope integrity, and sigmaE
      mediated envelope stress response in Stenotrophomonas maltophilia.
AB  - Resistance nodulation division (RND) efflux pumps, such as the SmeIJK pump of
      Stenotrophomonas maltophilia, are known to contribute to the multidrug resistance
      in Gram-negative bacteria. However, some RND pumps are constitutively expressed
      even though no antimicrobial stresses occur, implying that there should be some
      physical implications for these RND pumps. In this study, the role of SmeIJK in
      antimicrobials resistance, envelope integrity, and sigmaE-mediated envelope
      stress response (ESR) of S. maltophilia was assessed. SmeIJK was involved in the
      intrinsic resistance of S. maltophilia KJ to aminoglycosides and leucomycin.
      Compared with the wild-type KJ, the smeIJK deletion mutant exhibited growth
      retardation in the MH medium, an increased sensitivity to membrane-damaging
      agents (MDAs), as well as activation of an sigmaE-mediated ESR. Moreover, the
      expression of smeIJK was further induced by sub-lethal concentrations of MDAs or
      surfactants in an sigmaE-dependent manner. These data collectively suggested an
      alternative physiological role of smeIJK in cell envelope integrity maintenance
      and sigmaE-mediated ESR beyond the efflux of antibiotics. Because of the
      necessity of the physiological role of SmeIJK in protecting S. maltophilia from
      the envelope stress, smeIJK is constitutively expressed, which, in turn,
      contributes the intrinsic resistance to aminoglycoside and leucomycin. This is
      the first demonstration of the linkage among RND-type efflux pump, cell envelope
      integrity, and sigmaE-mediated ESR in S. maltophilia. 

PMID- 25390934
TI  - Whole-genome sequencing of the world's oldest people.
AB  - Supercentenarians (110 years or older) are the world's oldest people. Seventy
      four are alive worldwide, with twenty two in the United States. We performed
      whole-genome sequencing on 17 supercentenarians to explore the genetic basis
      underlying extreme human longevity. We found no significant evidence of
      enrichment for a single rare protein-altering variant or for a gene harboring
      different rare protein altering variants in supercentenarian compared to control
      genomes. We followed up on the gene most enriched for rare protein-altering
      variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second
      cohort of 99 long-lived individuals but did not find a significant enrichment.
      The genome of one supercentenarian had a pathogenic mutation in DSC2, known to
      predispose to arrhythmogenic right ventricular cardiomyopathy, which is
      recommended to be reported to this individual as an incidental finding according
      to a recent position statement by the American College of Medical Genetics and
      Genomics. Even with this pathogenic mutation, the proband lived to over 110
      years. The entire list of rare protein-altering variants and DNA sequence of all
      17 supercentenarian genomes is available as a resource to assist the discovery of
      the genetic basis of extreme longevity in future studies. 

PMID- 25390936
TI  - Digital multimedia books produced using iBooks Author for pre-operative surgical
      patient information.
AB  - Presenting patients with medical information and ensuring informed consent can be
      difficult due to patients with varying levels of literacy, physical and mental
      disabilities and spoken languages. Patients obtaining information from external
      sources, such as the internet, can also be problematic as the information can be
      irrelevant, inaccurate or misleading. A patient satisfaction study was performed
      in order to assess the effectiveness of using ebooks in order to communicate pre
      and post surgical information to neurosurgical patients. 3 digital books were
      produced using iBooks Author (a free desktop publishing program designed by
      Apple) including ACDF (anterior cervical discectomy and fusion), lumbar
      laminectomy and lumbar discectomy. Each book contained written information
      organised into sections and chapters along with an array of multimedia elements
      including 3D animations, interactive diagrams, 3D models of anatomy and patient
      experience videos. 32 volunteer patients were then presented with the digital
      books via an iPad during their preoperative assessment and then asked to complete
      a questionnaire. The results demonstrated a demand for this type of digital
      presentation of medical information and also showed patients no longer felt the
      need to seek further information from external sources.

PMID- 25390935
TI  - Structural and functional characterization of methicillin-resistant
      Staphylococcus aureus's class IIb fructose 1,6-bisphosphate aldolase.
AB  - Staphylococcus aureus is one of the most common nosocomial sources of soft-tissue
      and skin infections and has more recently become prevalent in the community
      setting as well. Since the use of penicillins to combat S. aureus infections in
      the 1940s, the bacterium has been notorious for developing resistances to
      antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). With the
      persistence of MRSA as well as many other drug resistant bacteria and parasites,
      there is a growing need to focus on new pharmacological targets. Recently, class
      II fructose 1,6-bisphosphate aldolases (FBAs) have garnered attention to fill
      this role. Regrettably, scarce biochemical data and no structural data are
      currently available for the class II FBA found in MRSA (SaFBA). With the recent
      finding of a flexible active site zinc-binding loop (Z-Loop) in class IIa FBAs
      and its potential for broad spectrum class II FBA inhibition, the lack of
      information regarding this feature of class IIb FBAs, such as SaFBA, has been
      limiting for further Z-loop inhibitor development. Therefore, we elucidated the
      crystal structure of SaFBA to 2.1 A allowing for a more direct structural
      analysis of SaFBA. Furthermore, we determined the KM for one of SaFBA's
      substrates, fructose 1,6-bisphosphate, as well as performed mode of inhibition
      studies for an inhibitor that takes advantage of the Z-loop's flexibility.
      Together the data offers insight into a class IIb FBA from a pervasively drug
      resistant bacterium and a comparison of Z-loops and other features between the
      different subtypes of class II FBAs. 

PMID- 25390937
TI  - Eupatorin-induced cell death in human leukemia cells is dependent on caspases and
      activates the mitogen-activated protein kinase pathway.
AB  - Eupatorin is a naturally occurring flavone that inhibits cell proliferation in
      human tumor cells. Here we demonstrate that eupatorin arrests cells at the G2-M
      phase of the cell cycle and induces apoptotic cell death involving activation of
      multiple caspases, mitochondrial release of cytochrome c and poly(ADP-ribose)
      polymerase cleavage in human leukemia cells. This flavonoid induced the
      phosphorylation of members of the mitogen-activated protein kinases and cell
      death was attenuated by inhibition of c-jun N-terminal kinases/stress activated
      protein kinases. Eupatorin-induced cell death is mediated by both the extrinsic
      and the intrinsic apoptotic pathways and through a mechanism dependent on
      reactive oxygen species generation. 

PMID- 25390938
TI  - Long-term microfouling on commercial biocidal fouling control coatings.
AB  - The current study investigated the microbial community composition of the
      biofilms that developed on 11 commercial biocidal coatings, including examples of
      the three main historic types, namely self-polishing copolymer (SPC), self
      polishing hybrid (SPH) and controlled depletion polymer (CDP), after immersion in
      the sea for one year. The total wet weight of the biofilm and the total bacterial
      density were significantly influenced by all coatings. Pyrosequencing of 16S rRNA
      genes revealed distinct bacterial community structures on the different types of
      coatings. Flavobacteria accounted for the dissimilarity between communities
      developed on the control and SPC (16%) and the control and SPH coatings (17%),
      while Alphaproteobacteria contributed to 14% of the dissimilarity between the
      control and CDP coatings. The lowest number of operational taxonomic units was
      found on Intersmooth 100, while the lowest biomass and density of bacteria was
      detected on other SPC coatings. The experiments demonstrated that the nature and
      quantity of biofilm present differed from coating to coating with clear
      differences between copper-free and copper-based biocidal coatings. 

PMID- 25390940
TI  - Accelerating the switchgrass (Panicum virgatum L.) breeding cycle using genomic
      selection approaches.
AB  - Switchgrass (Panicum virgatum L.) is a perennial grass undergoing development as
      a biofuel feedstock. One of the most important factors hindering breeding efforts
      in this species is the need for accurate measurement of biomass yield on a per
      hectare basis. Genomic selection on simple-to-measure traits that approximate
      biomass yield has the potential to significantly speed up the breeding cycle.
      Recent advances in switchgrass genomic and phenotypic resources are now making it
      possible to evaluate the potential of genomic selection of such traits. We
      leveraged these resources to study the ability of three widely-used genomic
      selection models to predict phenotypic values of morphological and biomass
      quality traits in an association panel consisting of predominantly northern
      adapted upland germplasm. High prediction accuracies were obtained for most of
      the traits, with standability having the highest ten-fold cross validation
      prediction accuracy (0.52). Moreover, the morphological traits generally had
      higher prediction accuracies than the biomass quality traits. Nevertheless, our
      results suggest that the quality of current genomic and phenotypic resources
      available for switchgrass is sufficiently high for genomic selection to
      significantly impact breeding efforts for biomass yield. 

PMID- 25390941
TI  - Hyperbolic discounting: value and time processes of substance abusers and non
      clinical individuals in intertemporal choice.
AB  - The single parameter hyperbolic model has been frequently used to describe value
      discounting as a function of time and to differentiate substance abusers and non
      clinical participants with the model's parameter k. However, k says little about
      the mechanisms underlying the observed differences. The present study evaluates
      several alternative models with the purpose of identifying whether group
      differences stem from differences in subjective valuation, and/or time
      perceptions. Using three two-parameter models, plus secondary data analyses of 14
      studies with 471 indifference point curves, results demonstrated that adding a
      valuation, or a time perception function led to better model fits. However, the
      gain in fit due to the flexibility granted by a second parameter did not always
      lead to a better understanding of the data patterns and corresponding
      psychological processes. The k parameter consistently indexed group and context
      (magnitude) differences; it is thus a mixed measure of person and task level
      effects. This was similar for a parameter meant to index payoff devaluation. A
      time perception parameter, on the other hand, fluctuated with contexts in a non
      predicted fashion and the interpretation of its values was inconsistent with
      prior findings that supported enlarged perceived delays for substance abusers
      compared to controls. Overall, the results provide mixed support for hyperbolic
      models of intertemporal choice in terms of the psychological meaning afforded by
      their parameters. 

PMID- 25390942
TI  - Profiling first-year students in STEM programs based on autonomous motivation and
      academic self-concept and relationship with academic achievement.
AB  - The low success rate of first-year college students in Science, Technology,
      Engineering, and Mathematics (STEM) programs has spurred many academic
      achievement studies in which explanatory factors are studied. In this study, we
      investigated from a person-oriented perspective whether different motivational
      and academic self-concept profiles could be discerned between male and female
      first-year college students in STEM and whether differences in early academic
      achievement were associated with these student groups. Data on autonomous
      motivation, academic self-concept, and early academic achievement of 1,400 first
      year STEM college students were collected. Cluster analyses were used to
      distinguish motivational profiles based on the relative levels of autonomous
      motivation and academic self-concept for male and female students. Differences in
      early academic achievement of the various profiles were studied by means of
      ANCOVA. Four different motivational profiles were discerned based on the
      dimensions of autonomous motivation (A) and academic self-concept (S): students
      scoring high and respectively low on both dimensions (HA-HS or LA-LS), and
      students scoring high on one dimension and low on the other (HA-LS or LA-HS).
      Also gender differences were found in this study: male students with high levels
      of academic self-concept and autonomous motivation had higher academic
      achievement compared to male students with low levels on both motivational
      dimensions. For female students, motivational profiles were not associated with
      academic achievement. The findings partially confirm the internal and external
      validity of the motivational theories underpinning this study and extend the
      present insights on identifying subgroup(s) of at risk students in contemporary
      STEM programs at university level. 

PMID- 25390943
TI  - Atypical unilateral maculopathy associated with acute exudative polymorphous
      vitelliform maculopathy-like yellowish deposits.
AB  - PURPOSE: To report a case of atypical unilateral maculopathy associated with
      acute exudative polymorphous vitelliform maculopathy-like yellowish deposits.
      METHODS: Observational case report of one patient. RESULTS: A 52-year-old man
      presented with reduced vision in the left eye. Findings resembling acute
      exudative polymorphous vitelliform maculopathy were noted with ophthalmoscopy,
      fluorescein angiography, and optical coherence tomography. Funduscopic
      examination revealed an exudative macular detachment with yellowish subretinal
      deposits inferior to the fovea. On fluorescein angiography, the perifoveal
      lesions were minimally hyperfluorescent, with no abnormal fluorescence in the
      central macula. The subretinal deposits were found to be hyperautofluorescent on
      fundus autofluorescence imaging. Optical coherence tomography confirmed a serous
      detachment of the retina with intraretinal cystic spaces. The right eye did not
      show any abnormalities except for an epiretinal membrane. CONCLUSION: We describe
      a case of atypical unilateral maculopathy associated with acute exudative
      polymorphous vitelliform maculopathy-like yellowish deposits.

PMID- 25390944
TI  - Accelerated diabetic retinopathy and late human immunodeficiency virus diagnosis.
AB  - PURPOSE: To describe a case of rapidly progressive diabetic retinopathy in a
      patient who is human immunodeficiency virus positive. METHODS: This is an
      observational case report. RESULTS: Fundus examination shows worsening of
      diabetic retinopathy with new vessels and vitreous hemorrhage in both eyes
      despite intense pan retinal photocoagulation. CONCLUSION: For patients with
      diabetes, additional diagnosis of human immunodeficiency virus increases the
      challenge of managing diabetic retinopathy as proliferation can appear rapidly
      and tends to worsen in these patients.

PMID- 25390945
TI  - Vitrectomy for proliferative retinopathy in patient with advanced duchenne
      muscular dystrophy.
AB  - PURPOSE: Retinal vascular abnormalities are rare in patients with Duchenne
      muscular dystrophy. We present a patient with Duchenne muscular dystrophy who
      developed severe proliferative retinopathy for which vitrectomy was successfully
      performed in one eye. METHOD: Case presentation. A 23-year-old Japanese man with
      Duchenne muscular dystrophy complicated by cardiac and respiratory insufficiency
      had reduced vision in both eyes. His best-corrected visual acuity was 0.01 in the
      right eye and hand movements in the left eye. Ophthalmoscopy showed vitreous
      hemorrhage and proliferative tissue attached to the optic disk bilaterally.
      Ultrasound echography showed tractional retinal detachment in the left eye.
      RESULTS: Because general anesthesia was considered to be a high risk, vitrectomy,
      lensectomy, neovascular membrane removal, endolaser photocoagulation, and
      silicone oil injection were performed under local anesthesia on the right eye.
      After removal of the silicone oil and intraocular lens implantation, the best
      corrected visual acuity was 0.8 in the right eye. Vitrectomy was performed on the
      left eye, but the retina could not be attached. CONCLUSION: The etiology of the
      proliferative retinopathy in our case is not known. Because early treatment has
      the potential to improve and maintain vision, we recommend periodic fundus
      examinations in patients with Duchenne muscular dystrophy.

PMID- 25390946
TI  - An unusual case of aicardi syndrome.
AB  - PURPOSE: Report of an unusual case of Aicardi syndrome. METHODS: Case report of
      an infant with severe chorioretinal lacunae and Aicardi syndrome. RESULTS:
      Despite severe chorioretinal lacunae, a 25-month-old white girl with infantile
      spasms/seizures had better visual acuity than expected. CONCLUSION: The extent of
      chorioretinal lesions is not necessarily a prognostic factor for visual function.

PMID- 25390947
TI  - Bilateral central retinal vein occlusion in a patient with disseminated
      metastatic renal cell carcinoma treated with sorafenib.
AB  - PURPOSE: The aim of the article is to report a case of a patient with
      disseminated metastatic renal cell carcinoma on long-term treatment with
      sorafenib who had developed bilateral central retinal vein occlusion over a
      period of 6 months. METHODS: A 73-year-old man with decreased visual acuity in
      the right eye and central retinal vein occlusion in the left eye 6 months
      previously. The patient had been on long-term treatment with the antiangiogenic
      drug, sorafenib for disseminated metastatic renal cell carcinoma-a highly
      vascularized tumor. The physical examination and fluorescein angiography showed a
      thrombus in the central retinal vein in the right eye and evidence of a past
      thrombus in the central retinal vein in the left eye. Numerous avascular zones in
      the retinas of both eyes were seen on angiography. The patient was prescribed
      anticoagulant medication and laser photocoagulation of the retina in both eyes
      and transscleral cryoapplication in the right retina were performed. RESULTS: The
      treatment resulted in stabilizing the visual acuity (best-corrected visual acuity
      of the right eye was 0.01, best-corrected visual acuity of the left eye was 0.06)
      and decreasing the number and extent of avascular zones in the retinas of both
      eyes. No reduction of the chronic macular edema was achieved in the right eye.
      CONCLUSION: The patient with disseminated metastatic renal cell carcinoma on long
      term sorafenib treatment should undergo periodic ophthalmologic examinations to
      exclude any potential vascular complications associated with cancer (vein
      occlusion associated with disseminated metastatic disease, tumor embolus, tumor
      thrombus) or with treatment (antiangiogenic drugs, steroids).

PMID- 25390948
TI  - Giant retinal tear after pneumatic retinopexy.
AB  - PURPOSE: To report a case with giant retinal tear after pneumatic retinopexy. To
      our knowledge, this is only the second case of a giant retinal tear after
      pneumatic retinopexy reported. METHODS: This is a descriptive case study.
      RESULTS: A 43-year-old myopic man underwent pneumatic retinopexy for right eye
      rhegmatogenous retinal detachment. Postoperative course was complicated by a
      giant retinal tear, which was treated successfully. CONCLUSION: Though rare,
      giant retinal tears can occur after pneumatic retinopexy. The likely mechanism is
      increased vitreous traction because of expansion of gas in a predisposed myopic
      eye.

PMID- 25390949
TI  - Bilateral viral retinitis in a patient with immune deficiency because of purine
      nucleoside phosphorylase deficiency.
AB  - BACKGROUND: Progressive retinal outer necrosis is a devastating viral necrotizing
      retinitis, which affects predominantly immunocompromised patients. We report a
      case in which the ocular findings led to a search for an underlying immune
      deficiency, established as congenital purine nucleoside phosphorylase deficiency.
      METHODS: Retrospective, interventional case report. RESULTS: We describe the
      clinical features and management of the disease. CONCLUSION: This is the first
      report of bilateral varicella zoster virus retinitis with underlying purine
      nucleoside phosphorylase deficiency. It highlights the importance of thorough
      investigation in apparent immunocompetent patients presenting with viral
      retinitis, as this may indicate an undiagnosed primary immunodeficiency.

PMID- 25390950
TI  - Amniotic membrane as single treatment in complication of exposed scleral buckle.
AB  - PURPOSE: To report a case of complicated exposed scleral buckle in which amniotic
      membrane was used to repair the extremely thin sclera that showed the underlying
      choroid. METHODS: Interventional case report. A 65-year-old man presented to our
      Department with severe eye pain after retinal detachment repair with scleral
      buckling technique 7 years ago. RESULTS: Examination of the left eye revealed
      extrusion of the buckle with conjunctival and scleral erosion that allowed
      distinguishing the choroid. The buckle was removed and successful scleral repair
      was achieved through the use of amniotic membrane. CONCLUSION: Amniotic membrane
      graft is a safe and useful scleral substitute that should be considered to cover
      scleral defects, in the absence of infection.

PMID- 25390951
TI  - Cancer-associated retinopathy in a patient with seminoma.
AB  - PURPOSE: The purpose of this study was to report our findings on a patient with
      cancer-associated retinopathy who had seminoma. METHODS: A 43-year-old man, who
      had been diagnosed with Stage 1 seminoma, complained of blurred vision. Fundus
      examination revealed attenuated retinal arteries, mild optic disk pallor, and a
      thinning of the outer nuclear layer. Ring scotomas were found in the visual
      fields of both eyes. The amplitudes of the electroretinograms were moderately
      reduced. The patient's serum was analyzed for antibodies. RESULTS: Antibodies
      against recoverin, Hu, and Ma-2 antigens were not detected. However, Western
      blots of the serum detected 2 bands at 41 and 64 kDa. The 41-kDa band was an anti
      retina-specific antibody. Immunoreactivity was identified in the photoreceptor
      layer of mice retinas. From these findings, we diagnosed the patient with cancer
      associated retinopathy. The visual functions remained stable after the removal of
      the primary lesion at an early stage, treatment with steroids, and intravenous
      immunoglobulin. CONCLUSION: This is the first case of cancer-associated
      retinopathy because of seminoma. The progression of the disease was reduced by
      removing the seminoma at an early stage, treatment with steroids, and intravenous
      immunoglobulin.

PMID- 25390952
TI  - Stellate neuroretinitis associated with posterior scleritis.
AB  - PURPOSE: To describe two cases of stellate neuroretinitis associated with
      posterior scleritis. METHODS: Retrospective observational case series. RESULTS:
      Two middle-aged female patients presented with unilateral decreased vision and
      clinical findings consistent with stellate neuroretinitis. A thorough diagnostic
      evaluation for known causes of neuroretinitis was negative in each case.
      Radiography, ultrasonography, and fluorescein angiography revealed findings
      consistent with a diagnosis of posterior scleritis in each patient. CONCLUSION:
      This is the first report of posterior scleritis causing stellate neuroretinitis.
      In patients with stellate neuroretinitis of unknown etiology, posterior scleritis
      should be considered in the differential diagnosis.

PMID- 25390953
TI  - Transient subretinal hemorrhage after photodynamic therapy of subfoveal choroidal
      osteoma.
AB  - PURPOSE: To report a case of choroidal osteoma that developed subretinal
      hemorrhage after photodynamic therapy (PDT). METHODS: Interventional case report.
      RESULTS: An 8-year-old boy was brought to our attention because of mild visual
      loss in his left eye. The visual acuity was 20/25. A subfoveal yellow-orange
      colored lesion, measuring 5.0 mm * 4.5 mm in base diameter was detected in the
      left eye. B-mode ultrasonography showed an acoustically solid 2.0-mm-thick mass
      with orbital shadowing. Orbital computed tomography confirmed the presence of
      calcium, and choroidal osteoma was diagnosed. As there was a decrease in the best
      corrected visual acuity (20/30) and the lesion showed growth (6.0 mm * 6.0 mm),
      PDT was performed at 6 months follow-up. The day after PDT, the visual acuity was
      counting fingers at 1 m and a subretinal hemorrhage over the lesion was detected.
      Two weeks after PDT, subfoveal hemorrhage dissappeared with some retinal pigment
      epithelial hyperplasia and visual acuity increased back to 20/30. CONCLUSION:
      Although PDT can induce decalcification in choroidal osteomas, it should not be
      performed in subfoveal osteomas unless there is evidence to treat the lesion such
      as the presence of choroidal neovascularization.

PMID- 25390954
TI  - Postsurgical sympathetic ophthalmia refractory to treatment: the response to
      infliximab.
AB  - PURPOSE: A clinical case of a postoperative sympathetic ophthalmia is presented
      and its response to the monoclonal antibody infliximab. PATIENTS: A 61-year-old
      woman. RESULTS: The treatment with prednisone, cyclosporine, azathioprine, and
      mycophenolate mofetil did not completely control the loss of visual acuity caused
      by the disease. Monthly intravenous infusions of infliximab (5 mg/kg)
      significantly improved the condition of the patient, allowing the cyclosporine
      and azathioprine to be withdrawn and the prednisone to be reduced to 10 mg/d.
      CONCLUSION: The use of the immunosuppressive drug infliximab in combination with
      prednisone improved the prognosis of a patient suffering from sympathetic
      ophthalmia. The reported effectiveness of infliximab in the treatment of T
      lymphocyte-mediated diseases suggests that it could be used earlier in cases of
      sympathetic ophthalmia when treatment with corticosteroids must be shortened.

PMID- 25390955
TI  - Uremic optic neuropathy with severe epiretinal membrane formation.
AB  - PURPOSE: The purpose of this study was to describe a patient with uremic optic
      neuropathy and concomitant epiretinal membrane formation. METHODS: The patient
      was investigated by standard ophthalmoscopy, blood samples, and by radiography.
      PATIENT: A 24-year-old woman with renal failure. RESULTS: Severe optic nerve head
      edema and massive epiretinal fibrosis with central retinal tractional detachment
      were found in both eyes. Surgical intervention resulted in attachment of the
      right retina, whereas the condition resulted in chronic detachment of the left
      retina despite repeated treatment. CONCLUSION: To our knowledge, the combination
      of uremic optic neuropathy and massive epiretinal membrane formation has not been
      described previously. Strategies for managing this severe visually threatening
      condition are discussed.

PMID- 25390956
TI  - Peripapillary choroidal neovascularization in best disease.
AB  - BACKGROUND: Best disease is an autosomal dominant retinal dystrophy with a
      variable phenotypic expression. Clinically, it is characterized by a vitelliform
      lesion in the macula because of the deposition of yellow material in a dome
      shaped configuration, believed to be lipofuscin that accumulates within and
      beneath the retinal pigment epithelium. Best disease is occasionally complicated
      by the development of choroidal neovascularization (CNV), which typically occurs
      in the macula. We report a case of peripapillary CNV in Best disease. METHODS:
      Interventional case report. RESULTS: A 12-year-old boy who was previously
      diagnosed with Best disease was treated with reduced fluence photodynamic therapy
      for subfoveal CNV in the right eye. After 2 months, he presented with
      peripapillary CNV in the left eye, which was treated with repeated sessions of
      reduced fluence photodynamic therapy. CONCLUSION: Ophthalmologists must be aware
      that peripapillary CNV may occasionally complicate Best disease and can be
      successfully treated with photodynamic therapy.

PMID- 25390957
TI  - Eclipse photodynamic therapy for a presumed peripapillary metastatic tumor.
AB  - PURPOSE: We report a successful use of a modified photodynamic therapy (PDT)
      termed Eclipse PDT in treating a patient with peripapillary metastatic choroidal
      tumor. METHODS: Optic disk protection effect was measured with different colored
      paper disk attached to the reflecting mirror of the laser machine. RESULTS: Black
      paper disk was chosen to perform Eclipse PDT because of its maximal blocking
      effect. A patient with peripapillary metastatic choroidal tumor was treated using
      this method, and the postoperative outcome was favorable, with improvement in
      visual acuity and resolution of subretinal fluid. CONCLUSION: With the new
      technique, treatment can be modified according to the lesion's shape and location
      without damaging the optic disk. Eclipse PDT can further extend the indication of
      PDT treatment to peripapillary choroidal neovascularization as well as choroidal
      tumors close to the optic disk.

PMID- 25390958
TI  - Resolution of a choroidal abscess in the setting of endophthalmitis in an
      immunocompetent host with noninvasive treatment.
AB  - PURPOSE: The purpose of this article was to report a case of Pseudomonas
      aeruginosa-related endophthalmitis associated with a choroidal abscess in an
      immunocompetent patient, with no history of lung disease or surgery that
      responded to noninvasive treatment and to compare it with other reported cases of
      P. aeruginosa-related choroidal abscesses. METHODS: A case report. PATIENT: An 89
      year-old immunocompetent man, with a history of hypertension, treated colon
      cancer, treated prostate cancer, total hip replacement, cataracts, a recent fall,
      and no history of cystic fibrosis or other lung disease, presents with swelling
      and congestion of the left eye, conjunctival ulcer, and with later findings of
      choroidal lesion. The lesions demonstrated pockets of mobile and nonmobile
      opacities, indicating a choroidal abscess. RESULTS: Noninvasive treatment with
      topical and intravenous antibiotics resulted in resolution of the abscess and
      improvement in visual acuity, while avoiding further retinal damage. Ocular
      ultrasonography showed that the therapeutic course was able to successfully
      decrease vitreous opacities, choroidal thickenings, and orbital irregularities.
      Blood cultures and ocular swabs were positive of P. aeruginosa. CONCLUSION: An
      elderly immunocompetent patient presenting with Pseudomonas endogenous
      endophthalmitis-associated choroidal abscess had favorable anatomical and visual
      outcomes after treatment with only intravenous and topical antibiotics.

PMID- 25390959
TI  - Combined central retinal vein and artery occlusion in systemic lupus
      erythematosus patient.
AB  - PURPOSE: To describe combined central retinal vein occlusion and central retinal
      artery occlusion in systemic lupus erythematosus patient. METHODS: An 18-year-old
      woman came to our clinic complaining of sudden marked visual loss in her right
      eye. Best-corrected visual acuity was only hand movement in the right eye. An
      examination of the right fundus revealed a pale and edematous retina with
      widespread flame hemorrhages, a swollen optic disk, engorged and tortuous retinal
      veins, and a cherry-red spot, leading to a diagnosis of combined central retinal
      vein occlusion and central retinal artery occlusion. Fluorescein angiography
      displayed disk edema and delayed arteriolar filling, with dilated veins that did
      not fill with fluorescein. Because of the presence of fever, she was referred to
      the department of internal medicine where she was diagnosed as having systemic
      lupus erythematosus and antiphospholipid syndrome. The patient received steroid
      and anticoagulant treatment. To prevent neovascular glaucoma, intense
      prophylactic panretinal photocoagulation was initiated 2 weeks later. RESULTS:
      Despite these efforts, consequent retinal neovascularization and neovascular
      glaucoma were unavoidable. Filtering surgery was performed 1 month after
      prophylactic panretinal photocoagulation. CONCLUSION: Although rare, combined
      central retinal vein and artery occlusion can occur in systemic lupus
      erythematosus patient.

PMID- 25390939
TI  - MicroRNA related polymorphisms and breast cancer risk.
AB  - Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs
      (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene
      expression regulation, which has been implicated in various cancers, including
      breast cancer, and may alter individual susceptibility to cancer. We investigated
      associations between miRNA related SNPs and breast cancer risk. First we
      evaluated 2,196 SNPs in a case-control study combining nine genome wide
      association studies (GWAS). Second, we further investigated 42 SNPs with
      suggestive evidence for association using 41,785 cases and 41,880 controls from
      41 studies included in the Breast Cancer Association Consortium (BCAC). Combining
      the GWAS and BCAC data within a meta-analysis, we estimated main effects on
      breast cancer risk as well as risks for estrogen receptor (ER) and age defined
      subgroups. Five miRNA binding site SNPs associated significantly with breast
      cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88
      0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94
      0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI:
      1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1,
      respectively. DROSHA belongs to miRNA machinery genes and has a central role in
      initial miRNA processing. The remaining genes are involved in different molecular
      functions, including apoptosis and gene expression regulation. Further studies
      are warranted to elucidate whether the miRNA binding site SNPs are the causative
      variants for the observed risk effects. 

PMID- 25390960
TI  - Spectral-domain optical coherence tomographic findings in punctate inner
      choroidopathy.
AB  - PURPOSE: To investigate the pathology of punctate inner choroidopathy (PIC) using
      spectral-domain optical coherence tomography. METHODS: We retrospectively
      reviewed spectral-domain optical coherence tomography findings of 14 cases with
      active PIC. We obtained specific appearance of the active PIC lesion that were
      characterized by yellowish/white round spots in fundus examination with
      fluorescein leakage. Fluorescein angiogram and confocal indocyanine green
      angiogram were also reviewed. RESULTS: Three cases (21%) of 14 were found to have
      specific findings. Case 1 was a 33-year-old woman who showed old choroidal
      neovascularization and active PIC. Spectral-domain optical coherence tomography
      showed multiple pigment epithelial detachments with hyperreflective contents and
      an irregular faint hyperreflective signal at the outer retina. The blurred vision
      resolved without treatment, at which time all the pathologies resolved. Case 2
      was a 42-year-old woman who showed previously treated choroidal
      neovascularization and active PIC. Spectral-domain optical coherence tomography
      disclosed small retinal pigment epithelium breaks through which sub-retinal
      pigment epithelium material migrated into the outer retina. The patient was
      observed, and the best-corrected visual acuity improved. Case 3 was a 32-year-old
      woman who showed obsolete PIC. Spectral-domain optical coherence tomography
      disclosed a retinal pigment epithelium defect. CONCLUSION: Multiple pigment
      epithelial detachments filled with hyperreflective material presumed to be
      because of inflammatory product and faint signals at the outer retina are common
      in active phase of PIC. These signs disappear according to the resolution of
      acute phase.

PMID- 25390961
TI  - Choroidal neovascularization secondary to sorsby fundus dystrophy treated with
      intravitreal bevacizumab.
AB  - PURPOSE: To report a case of extrafoveal choroidal neovascularization secondary
      to Sorsby fundus dystrophy that maintained 20/20 visual acuity over 14 months
      with intravitreal bevacizumab therapy. METHODS: Interventional case report of as
      needed treatment with intravitreal bevacizumab of a 38-year-old lady with
      choroidal neovascularization from Sorsby fundus dystrophy. RESULTS: Three
      injections of intravitreal bevacizumab were given over 14.5 months, maintaining
      visual acuity at 20/20. CONCLUSION: Intravitreal bevacizumab therapy appears to
      maintain vision in patients with choroidal neovascularization from Sorsby fundus
      dystrophy.

PMID- 25390962
TI  - Spectral-Domain OPTICAL COHERENCE TOMOGRAPHY of a Macular Fold AFTER Retinal
      Detachment Repair.
AB  - PURPOSE: We report a case with a dry macular fold after retinal detachment repair
      using spectral-domain optical coherence tomography images (SD-OCT) to evaluate
      details of the retinal architecture before and after surgical management.
      METHODS: A 62-year-old man diagnosed with macula-threatening rhegmatogenous
      retinal detachment underwent primary vitrectomy with an encircling sclera buckle.
      On post-operative day 5, he was noted to have developed a juxtafoveal retinal
      fold. SD-OCT was used to image the retinal fold and documented apposition of the
      retinal layers and discontinuity within the photoreceptor layer in the vicinity
      of the retinal fold. RESULTS: The attempts to detach and unfold the retina
      appeared minimally successful intraoperatively. However, as the gas bubble
      decreased, the retinal fold was noted to have resolved. Repeat SD-OCT documented
      flattening of the retinal fold with a well-preserved photoreceptor layer.
      CONCLUSION: This outcome suggests the possibility of delayed postoperative
      success in flattening a retinal fold despite resistance to manipulation and
      failed attempts during the course of the surgery. To our knowledge, this is the
      first report that demonstrates this finding within the macular architecture after
      retinal detachment surgery in vivo using spectral-domain optical coherence
      tomography. These findings may have an important role in management of these
      cases and may become prognostic indicators based on the alterations in retinal
      anatomy demonstrated by high-resolution imaging.

PMID- 25390963
TI  - Microperimetry and optical coherence tomography in acute macular
      neuroretinopathy.
AB  - PURPOSE: To report optical coherence tomography and microperimetry findings in
      acute macular neuroretinopathy. METHODS: Case report. PATIENTS: A single patient
      with acute macular neuroretinopathy. CONCLUSION: Scotomata reported by a patient
      with acute macular neuroretinopathy correspond with findings of disruption of the
      photoreceptor inner segment-outer segment junction on optical coherence
      tomography and congruent decreased retinal function demonstrated with
      microperimetry.

PMID- 25390964
TI  - A unique posterior segment manifestation of whipple disease.
AB  - PURPOSE: To report a novel posterior segment manifestation of Whipple disease.
      METHOD: Single observational case study. RESULTS: The white crystalline deposit
      in the retina, choroiditis, and vitritis resolved with treatment of Whipple
      disease. CONCLUSION: Whipple disease can be associated with panuveitis,
      multifocal choroiditis, and white crystalline deposits in the anterior segments
      and retina, a unique clinical finding.

PMID- 25390965
TI  - Novel retinal findings in an infant with muscle-eye-brain disease.
AB  - PURPOSE: To describe novel retinal findings in an infant with muscle-eye-brain
      disease and suggest a novel mechanism for congenital retinal detachment. METHODS:
      Case report. RESULTS: A 7-week-old, white, female infant presented with total
      retinal detachment, peripheral retinal avascularity, and neovascularization of
      the right eye. In the left eye, there was hypoplastic optic nerve, no
      identifiable foveal avascular zone, and a small area of avascularity in the
      temporal peripheral retina. Genetic testing ultimately confirmed the diagnosis of
      muscle-eye-brain disease, a disorder of aberrant neuronal migration. CONCLUSION:
      This case describes retinal findings that, to our knowledge, have not been
      reported in previous cases of muscle-eye-brain disease: peripheral avascularity,
      leading to retinal detachment in one eye, and foveal dysplasia. It is speculated
      that aberrant retinal vasculogenesis arose from disordered migration and
      patterning of retinal neurons.

PMID- 25390966
TI  - Intraarterial chemotherapy for kissing macula tumors in retinoblastoma.
AB  - PURPOSE: To describe the management of kissing macula retinoblastoma tumors
      treated with intraarterial chemotherapy. METHODS: Superselective infusion of
      chemotherapy (combinations of melphalan, topotecan, and carboplatin) into the
      ophthalmic artery of children with retinoblastoma who had kissing macula tumors
      was administered on an outpatient basis. Results were assessed with indirect
      ophthalmoscopy, RetCam digital photography, B-scan ultrasonography, and
      electroretinograms. Three children with bilateral retinoblastoma (aged 6.1, 7,
      and 16 months) and kissing macula tumors in an eye were treated. RESULTS: All
      children are alive without the need for removal of the eye, systemic
      chemotherapy, or external beam irradiation. In each case, the kissing tumors
      retracted, leaving an anatomically normal fovea. Final 30-Hz flicker
      electroretinograms were 93.9, 65, and 63.9 MUV (under anesthesia). There were no
      significant systemic toxicities. CONCLUSION: Superselective infusion of
      chemotherapy by means of the ophthalmic artery of young children with kissing
      macula tumors resulted in prompt shrinkage of tumors away from the fovea. There
      were no systemic side effects.

PMID- 25390967
TI  - Central retinal artery occlusion secondary to optic disk melanocytoma.
AB  - PURPOSE: To report a case of central retinal artery occlusion with cilioretinal
      artery sparing associated with an optic disk melanocytoma. METHODS: Retrospective
      observational case report. RESULTS: A 29-year-old healthy male adult presented
      with sudden profound visual loss in the right eye since the past 3 days. His
      medical history was unremarkable with no history of antecedent trauma. Best
      corrected visual acuity was 6/36 in the right eye and 6/6 in the left eye. The
      left eye was essentially normal. Right afferent pupillary defect was noted.
      Biomicroscopic examination of right fundus revealed an elevated, deeply
      pigmented, brown-black mass lesion over the optic disk, suggestive of
      melanocytoma. Other fundus findings were suggestive of central retinal artery
      occlusion with cilioretinal artery sparing. Clinical findings were confirmed on
      fundus fluorescein angiography, optical coherence tomography, ultrasonography,
      and visual field testing. Severe visual loss can occur because of retinal
      vascular occlusion in eyes with optic disk melanocytoma. CONCLUSION: Rapid visual
      loss and retinal vascular occlusion associated with optic disk melanocytoma may
      not necessarily be caused by its malignant transformation. It may be caused by
      tumor necrosis itself. Although rare, it is still important to follow-up such
      patients closely to look for signs suggestive of malignant transformation.

PMID- 25390968
TI  - Pseudovasculitis associated with vitreoretinal traction.
AB  - PURPOSE: The purpose of this study was to report a case of vitreoretinal traction
      masqueraded as retinal vasculitis. METHODS: An 81-year-old woman with exudative
      age-related macular degeneration was treated with intravitreal injections of
      ranibizumab. During routine follow-up, angiographic evidence of focal, segmental,
      retinal vasculitis, involving both arteries and veins, was noticed in the fellow
      eye. Clinical examination revealed no sign of ocular inflammation in either eye.
      RESULTS: Spectralis optical coherence tomography revealed partial posterior
      vitreous detachment with multiple areas of persisting vitreoretinal adhesion.
      Focal vasculitis on fluorescein angiography showed absolute correspondence with
      sites of vitreoretinal traction on optical coherence tomography. Patient was
      managed by observation and 6 months later, despite persisting fluorescein leak,
      she was still asymptomatic with no evidence of anterior chamber or vitreous
      activity. CONCLUSION: This is an exceptional case of pseudovasculitis associated
      with mechanical traction, representing a variant of vitreomacular traction
      syndrome. Clinicians should be aware of this unusual manifestation, which may
      mimic true vasculitis associated with uveitis.

PMID- 25390969
TI  - Diversity and distribution of arbuscular mycorrhizal fungi along altitudinal
      gradients in Mount Taibai of the Qinling Mountains.
AB  - Elevational patterns of plant and animal diversity have been studied for
      centuries; however, the effects of land elevation on arbuscular mycorrhizal (AM)
      fungal diversity remains unclear. We examined AM fungal diversity and
      distribution along 19 elevation belts in Mount Taibai of the Qinling Mountains,
      with the aim to assess the altitudinal diversity patterns. In total, 63 AM fungal
      taxa belonging to 12 genera were discovered. Mycorrhizal colonization rates on
      roots; AM fungal spore density; and fungal species richness, evenness, and
      diversity had different patterns in terms of the changes of elevation. Root
      colonization followed a cubical parabolic pattern, with a peak and a foot at an
      elevation of about 2000 and 3000 m above sea level, respectively. Species
      richness decreased monotonically from the lowest to the highest elevations. Spore
      density and alpha-diversity exhibited a unimodal pattern and peaked at an
      elevation of 2107 and 1350 m, respectively. Species evenness increased
      monotonically at an elevation of between 1050 and 2250 m. beta-Diversity also
      presented a basically incremental pattern along altitudinal gradients. Our
      findings suggest that elevation changes were the main factor governing the
      patterns of AM fungal diversity.

PMID- 25390971
TI  - Patterning vascular networks in vivo for tissue engineering applications.
AB  - The ultimate design of functionally therapeutic engineered tissues and organs
      will rely on our ability to engineer vasculature that can meet tissue-specific
      metabolic needs. We recently introduced an approach for patterning the formation
      of functional spatially organized vascular architectures within engineered
      tissues in vivo. Here, we now explore the design parameters of this approach and
      how they impact the vascularization of an engineered tissue construct after
      implantation. We used micropatterning techniques to organize endothelial cells
      (ECs) into geometrically defined "cords," which in turn acted as a template after
      implantation for the guided formation of patterned capillaries integrated with
      the host tissue. We demonstrated that the diameter of the cords before
      implantation impacts the location and density of the resultant capillary network.
      Inclusion of mural cells to the vascularization response appears primarily to
      impact the dynamics of vascularization. We established that clinically relevant
      endothelial sources such as induced pluripotent stem cell-derived ECs and human
      microvascular endothelial cells can drive vascularization within this system.
      Finally, we demonstrated the ability to control the juxtaposition of parenchyma
      with perfused vasculature by implanting cords containing a mixture of both a
      parenchymal cell type (hepatocytes) and ECs. These findings define important
      characteristics that will ultimately impact the design of vasculature structures
      that meet tissue-specific needs. 

PMID- 25390970
TI  - IL-6 receptor alpha defines effector memory CD8+ T cells producing Th2 cytokines
      and expanding in asthma.
AB  - RATIONALE: Cytokine receptors can be markers defining different T-cell subsets
      and considered as therapeutic targets. The association of IL-6 and IL-6 receptor
      alpha (IL-6Ralpha) with asthma was reported, suggesting their involvement in
      asthma. OBJECTIVES: To determine whether and how IL-6Ralpha defines a distinct
      effector memory (EM) CD8+ T-cell population in health and disease. METHODS: EM
      CD8+ T cells expressing IL-6Ralpha (IL-6Ralpha(high)) were identified in human
      peripheral blood and analyzed for function, gene, and transcription factor
      expression. The relationship of these cells with asthma was determined using
      blood and sputum. MEASUREMENTS AND MAIN RESULTS: A unique population of IL
      6Ralpha(high) EM CD8+ T cells was found in peripheral blood. These cells that
      potently proliferated, survived, and produced high levels of the Th2-type
      cytokines IL-5 and IL-13 had increased levels of GATA3 and decreased levels of T
      bet and Blimp-1 in comparison with other EM CD8+ T cells. In fact, GATA3 was
      required for IL-6Ralpha expression. Patients with asthma had an increased
      frequency of IL-6Ralpha(high) EM CD8+ T cells in peripheral blood compared with
      healthy control subjects. Also, IL-6Ralpha(high) EM CD8+ T cells exclusively
      produced IL-5 and IL-13 in response to asthma-associated respiratory syncytial
      virus and bacterial superantigens. CONCLUSIONS: Human IL-6Ralpha(high) EM CD8+ T
      cells is a unique cell subset that may serve as a reservoir for effector CD8+ T
      cells, particularly the ones producing Th2-type cytokines, and expand in asthma.

PMID- 25390973
TI  - Short-term effects of intravitreal bevacizumab in type ii idiopathic macular
      telangiectasia.
AB  - PURPOSE: To report the effect of intravitreal bevacizumab in type 2 idiopathic
      macular telangiectasia (type 2 IMT). DESIGN: Interventional case report. METHODS:
      A 51 year-old female patient with type 2 IMT presented with gradual visual
      deterioration and reading difficulties. In one affected eye, two intravitreal
      bevacizumab injections were performed with a four weeks interval. Examinations
      included ETDRS visual acuity, slit-lamp biomicroscopy, digital fluorescein
      angiography, optical coherence tomography (OCT) and microperimetry at baseline
      and during a 12-week review period. RESULTS: Following treatment the patient
      noted a visual improvement particularly during reading. On angiography a
      reduction in size and intensity of the hyperfluorescent area was recorded and the
      retinal sensitivity improved on microperimetry. CONCLUSIONS: In absence of other
      efficacious therapeutic modalities, the observations indicate a beneficial
      therapeutic effect of intravitreal bevacizumab in type2-IMT, and implicate a
      pathophysiological role of VEGF in this disease entity.

PMID- 25390972
TI  - Open, laparoscopic, and robotic ureteroneocystotomy for benign and malignant
      ureteral lesions: a comparison of over 100 minimally invasive cases.
AB  - INTRODUCTION: Laparoscopic (LAP) and robot-assisted laparoscopic (RAL) approaches
      have been applied to ureteroneocystostomies (UNC) although such experience has
      been limited to a small number of patients and limited follow-up. Herein, we
      detail our experience with over 100 minimally invasive UNC, the largest such
      series to date. METHODS: All minimally invasive UNC performed at our institution
      between 1997 and 2013 and all open UNC performed between 2008 and 2013 were
      identified. Perioperative parameters of relevance were identified and recorded.
      Chi-squared and ANOVA with post hoc Tukey analysis were performed for all
      categorical and continuous variables, respectively. RESULTS: A total of 130
      patients met our study criteria. One hundred five underwent the minimally
      invasive approach (20 RAL and 85 LAP). Mean follow-up duration was 504 days.
      Patients in the RAL, LAP, and open cohorts were of similar age, gender and
      laterality distribution, American Society of Anesthesiologists (ASA) score, body
      mass index, history of previous abdominal surgery, history of prior treatment for
      the ureteral lesion, and surgical indication ( Table 1 ). Operative time was
      similar across all cohorts (235-257 minutes, p=0.123). Estimated blood loss (EBL)
      was significantly lower in the RAL and LAP cohorts (100 and 150 mL) compared to
      their open counterparts (300 mL, p=0.001) although a decrease in hematocrit was
      similar across all groups. Only four intraoperative complications (4.7%) and two
      (2.4%) conversions to open were identified in the LAP group, without statistical
      significance. No intraoperative complications or conversions were identified in
      the RAL or open cohorts. Median length of stay (LOS) was significantly shorter in
      the minimally invasive cohorts compared to open (p<0.002). Ninety-day readmission
      rates (18.8-20%), major complications (10-20%), and failure rates (5.9-16%) were
      highest in the open cohort although without statistical significance. CONCLUSION:
      RAL or LAP UNC is feasible, safe, and comparable to the open technique with some
      perioperative benefit in EBL, LOS, and stent duration.

PMID- 25390974
TI  - Intravitreal bevacizumab (avastin) in a pediatric case of pathologic myopia.
AB  - PURPOSE: To report the successful consecutive use of intravitreal bevacizumab
      (Avastin) in a child with myopic choroidal neovascular membrane (mCNVM). METHOD:
      A 12-year-old child presented with gradual diminution of vision in both eyes.
      Ocular examination revealed pathologic myopia with mCNVMs in both eyes. Leakage
      was demonstrated on fluorescein angiography in right eye at the first visit,
      followed by the left eye 1 week later. A single injection of bevacizumab
      (Avastin) 1.25 mg (0.05 mL) was administered under aseptic precautions using a 30
      G needle in each eye separated by duration of 1 week. There were no complications
      during or after each procedure RESULTS: : Leakage from the mCNVM was reduced in
      both eyes within 2 weeks after the injections and there was reduction of macular
      thickness in both eyes. However, visual acuity change was modest, with the right
      eye improving from Snellen acuity of 1/60 before injection to 6/60 and the left
      eye remaining stable at 3/60. CONCLUSION: Intravitreal Avastin was safely
      injected successively in each eye in a pediatric case of pathologic myopia with
      mCNVM. Reduction of leakage and macular thickening may not be associated with
      commensurate visual improvement as in our case. Long-term safety and appropriate
      dosage of intravitreal bevacizumab needs to be studied before routine use in
      pediatric cases of neovascularization.

PMID- 25390975
TI  - INTRAVITREAL BEVACIZUMAB (AVASTIN) FOR TREATMENT OF PERSISTENT MACULAR EDEMA IN
      VITRECTOMIZED EYES: Limited Effect and Early Recurrence.
AB  - PURPOSE: To determine the effect of an intravitreal injection of bevacizumab on
      visual acuity of and foveal thickness in vitrectomized eyes with persistent
      macular edema. METHODS: Bevacizumab (1.25 mg/0.05 mL) was injected into the
      vitreous of 10 eyes of 10 patients with macular edema that persisted after
      vitrectomy. Seven eyes had macular edema associated with diabetic retinopathy,
      and three eyes had branch retinal vein occlusion. Main outcome measures were
      foveal thickness measured by optical coherence tomography and best-corrected
      visual acuity before and 1 week, 1 month, 2 months, and 3 months after the
      injection. RESULTS: Foveal thickness was reduced by 15% at 1 week after
      bevacizumab injection but returned to the pretreatment level by 1 month.
      Improvement in logarithm of the minimal angle of resolution (logMAR) visual
      acuity after the injection was not significant, and only one eye had improvement
      (>0.2 logMAR) of visual acuity at 3 months. CONCLUSION: These results indicate
      that intravitreal bevacizumab therapy is limited for eyes with macular edema that
      persists after vitrectomy.

PMID- 25390976
TI  - Intravitreal bevacizumab (avastin) for radiation retinopathy 53 years after
      treatment of retinoblastoma.
AB  - PURPOSE: To report the successful treatment of rubeosis and an atypical
      polypoidal vascular lesion in a case of radiation retinopathy treated with
      intravitreal bevacizumab. METHODS: A 56-year-old woman with a history of
      retinoblastoma treated with radiation in the right eye was followed up for a
      progressively enlarging lesion in the macula that was associated with subretinal
      fluid. The patient was examined with serial ultrasound and clinical examinations
      and underwent pupilloplasty on the right eye to improve the view to her fundus.
      Fluorescein angiography revealed a vascular lesion with prominent saccular
      dilations. Her subsequent course was complicated by a retinal vein occlusion,
      rubeosis, and decreased vision. RESULTS: A single treatment with intravitreal
      bevacizumab resulted in regression of the rubeosis and atypical polypoidal
      vascular lesion and subjective improvement in vision, which persisted for 3
      months. CONCLUSION: Rubeosis and atypical polypoidal neovascularization are known
      complications of radiation retinopathy, and treatment with intravitreal
      bevacizumab may be beneficial.

PMID- 25390977
TI  - Multiple repeated intravitreal triamcinolone treatments for radiation-induced
      macular edema.
AB  - BACKGROUND AND PURPOSE: This report discusses a patient with a predictably and
      repetitively favorable anatomic and functional response to intravitreal
      triamcinolone for radiation-induced macular edema. The purpose of this report is
      to demonstrate a situation where this treatment may have a favorable outcome over
      time. METHOD: Retrospective interventional case study. RESULT: Restoration of
      normal macular contour as well as maintenance of good vision after several
      treatments with intravitreal triamcinolone. CONCLUSION: Intravitreal
      triamcinolone is a well-established treatment for macular edema. In the vast
      majority of cases, its effect is transient, and additional treatments are
      necessary. It is important to realize that, in certain cases which are
      effectively treated with this modality, it may allow for preservation of good
      vision over time. One must be vigilant for the known complications of
      intravitreal triamcinolone, especially increased intraocular pressure and
      cataract progression.

PMID- 25390978
TI  - Cytomegalovirus retinitis after intravitreous triamcinolone treatment of a
      vitrectomized eye in an immunocompetent patient.
AB  - PURPOSE: To report a case of cytomegalovirus (CMV) retinitis after intravitreous
      injection of triamcinolone for a vitrectomized eye in an immunocompetent patient.
      DESIGN: Observational case report. METHODS: Review of medical records. RESULTS: A
      54-year-old woman with well-controlled type 2 diabetes developed anterior
      uveitis, papillitis, retinal vasculitis, and retinal exudates 3 months after
      intravitreous triamcinolone for the treatment of recurred macular edema. The
      intravitreal white mass of triamcinolone was ophthalmoscopically observed on the
      inferior peripheral retina. Polymerase chain reaction of the vitreous was
      positive for CMV DNA. There was no sign of systemic CMV infection. Laboratory
      examination revealed that the patient was a human T cell lymphotropic virus type
      1 carrier and HIV negative. The retinitis responded well to systemic ganciclovir
      and intravitreous foscarnet, but the treatment of anterior uveitis and vitreous
      opacity needed repeated vitreous surgery. CONCLUSION: CMV retinitis can occur
      after intravitreous triamcinolone for a vitrectomized eye in an immunocompetent
      patient.

PMID- 25390979
TI  - Cytomegalovirus retinitis after treatment with intravitreal triamcinolone
      acetonide in an immunocompetent patient.
AB  - PURPOSE: To describe a case of cytomegalovirus (CMV) retinitis following
      intravitreal triamcinolone acetonide (IVTA) in an immunocompetent patient.
      METHODS: A 77-year-old man with a history of diabetes mellitus developed retinal
      whitening with a vasculitis 6 weeks after receiving IVTA in the left eye. A
      vitreous biopsy was performed. RESULTS: Polymerase chain reaction was positive
      for CMV (419,000 copies/mL). A complete medical evaluation, including a negative
      test for human immunodeficiency virus, showed no systemic evidence of
      immunosuppression except for a highly elevated hemoglobin A1C level. CONCLUSION:
      CMV retinitis may be a rare complication of IVTA, possibly due to local ocular
      immunosuppression from the steroid medication. Poorly controlled diabetes
      mellitus may have contributed to this development.

PMID- 25390980
TI  - Necrotizing herpetic retinopathy after intravitreal triamcinolone acetonide
      injection.
AB  - PURPOSE: To report a new complication of intravitreal triamcinolone acetonide
      (TA) injection. METHODS: In this observational case report, an 87-year-old woman
      received an intravitreal injection of TA as an adjunct to photodynamic therapy
      for wet age-related macular degeneration in the left eye. Four months later, she
      developed ipsilateral necrotizing herpetic retinopathy (NHR). RESULTS: Retinal
      whitening of the macula was noted in the absence of vitritis that progressed over
      5 days to diffuse retinitis with moderate vitritis and anterior chamber cell.
      Visual acuity decreased from 20/30 to 20/400. TA was still present inferiorly in
      the vitreous cavity. Polymerase chain reaction testing of samples obtained by
      vitrectomy with vitreous aspiration and retinal biopsy demonstrated varicella
      zoster virus DNA. Two weeks later, repeated vitrectomy, silicone oil injection,
      and implantation of a ganciclovir sustained-release device were performed. Final
      visual acuity was 5/200. CONCLUSIONS: NHR can develop as a complication of
      intravitreal TA injection in an eye with a history of herpes zoster ophthalmicus.

PMID- 25390981
TI  - Four-month back pain after verteporfin treatment: clinical case notes.
AB  - OBJECTIVE: To describe the case of a patient with long-term back pain post
      verteporfin injection for photodynamic therapy. METHODS: Clinical case
      description from a metropolitan ophthalmic practice. RESULTS: Following injection
      of verteporfin, the patient developed continuous severe back pain. The back pain
      resolved over 4 months, and despite thorough orthopaedic and neurologic work-up,
      no other explanation was found. CONCLUSION: The temporal association of pain with
      verteporfin treatment, combined with a failure to identify an alternate cause,
      led the authors to attribute the patient's back pain to photodynamic therapy
      treatment.

PMID- 25390982
TI  - Focal detachment of fovea in patients with idiopathic epiretinal membrane.
AB  - PURPOSE: To report three cases of focal foveal detachment evident by optical
      coherence tomography (OCT) in idiopathic epiretinal membrane (ERM). METHODS: A
      retrospective case series of three patients who had focal foveal detachment shown
      by OCT and recent visual deterioration and metamorphopsia due to idiopathic ERM.
      RESULTS: Three patients with idiopathic ERM had recent visual deterioration and
      metamorphopsia. Although fundus examination, fluorescein angiography, and central
      macular thickness findings were stable, focal foveal detachment was identified by
      OCT in all patients. CONCLUSION: Our findings suggest a sequence of events to
      explain the OCT findings for and visual changes in these three patients. It is
      probable that contraction of the ERM on the surface of the retina may have led to
      dragging of the outer structure in the retina, resulting in focal detachment of
      the fovea.

PMID- 25390983
TI  - Secondary proliferations in heavy silicone oil endotamponade.
AB  - PURPOSE: To describe postoperative complications in a patient with a giant
      retinal tear and heavy silicone oil endotamponade. METHODS: Case report. RESULTS:
      A 16-year-old girl with a giant retinal tear underwent 20-gauge three-port pars
      plana vitrectomy with scleral buckling and heavy silicone oil endotamponade
      (Oxane HD; Bausch & Lomb, Toulouse, France). During follow-up, early
      emulsification of the silicone oil and severe secondary membrane proliferation
      within the silicone oil and retinal interface were detected. Exchange of silicone
      oil (5,000 centistokes) and membrane removal were performed. Histologic
      evaluation revealed fibrosis and a foreign body-type reaction. CONCLUSION:
      Secondary proliferations may become a provoked inflammatory response to heavy
      silicone oil; therefore, further controlled clinical trials should be performed
      to evaluate these potential side effects before heavy silicone oil is routinely
      used as a temporary vitreous substitute in eyes with complicated retinal
      detachments.

PMID- 25390984
TI  - Choroidal neovascularization in peripapillary acute zonal occult outer
      retinopathy.
AB  - BACKGROUND: Acute zonal occult outer retinopathy (AZOOR) is a disease of unknown
      etiology in young or middle-aged patients that is characterized by acute loss of
      one or more zones of outer retinal function, photopsia, minimal initial
      ophthalmoscopic changes, and electroretinographic abnormalities. AZOOR may
      represent part of the spectrum of a single disease, the so-called AZOOR complex.
      In contrast with most other ocular diseases that may be part of this AZOOR
      complex, AZOOR has not, to our knowledge, been reported in association with
      choroidal neovascularization (CNV). CASE REPORT: We describe a 47-year-old man
      presenting with peripapillary AZOOR and CNV. Despite photodynamic therapy, CNV
      evolved to a fibrovascular diskiform scar. CONCLUSION: The occurrence of CNV on
      the margin of the AZOOR process suggested a direct link between the CNV and the
      underlying condition. To our knowledge, this is the first reported case of CNV
      complicating AZOOR.

PMID- 25390985
TI  - Unilateral cone dysfunction as a manifestation of acute zonal occult outer
      retinopathy.
AB  - PURPOSE: To report a patient with unilateral cone dysfunction (UCD) who later
      developed acute zonal occult outer retinopathy (AZOOR) in the contralateral eye.
      METHODS: A 19-year-old Japanese woman was referred complaining of decreased
      vision and photopsia of the left eye. Static perimetry, full-field
      electroretinography (ERG), and multifocal ERGs (mfERGs) were performed to
      evaluate her visual functions. She returned 9 months later with visual field
      defect and photopsia in the right eye. RESULTS: The static visual field of the
      left eye demonstrated a scotoma that extended from the physiologic blind spot to
      the center of the visual field. The cone full-field ERGs were extinguished with
      preservation of rod function. The mfERGs were reduced throughout the posterior
      pole of the left eye. The patient was diagnosed with UCD. She revisited us 9
      months later complaining of visual symptoms in the right eye and was found to
      have an arcuate scotoma in the upper visual field corresponding to decreased
      mfERGs. These findings were consistent with clinical signs of AZOOR. CONCLUSION:
      These findings indicate that UCD is one of the clinical manifestations of AZOOR.

PMID- 25390986
TI  - An in vivo human demonstration of 23 gauge infusion cannula air forces striking
      the retina during a fluid/air exchange vitrectomy for macular hole repair.
AB  - PURPOSE: To demonstrate, in vivo, that infusion cannula forces of air may strike
      the retina and optic nerve, which may explain why some patients develop post
      vitrectomy scotomas. DESIGN: Case report. METHODS: During a vitrectomy for a
      macular hole, following a subtotal fluid/air exchange using a 23-gauge infusion
      cannula and a 25-gauge chandelier light, an unusual circular light reflex was
      noted on the surface of the retina inferior and nasal to the optic nerve.
      RESULTS: The light reflex appeared at a position opposite the infusion cannula;
      rotating the direction of the infusion cannula moved the reflex from an area
      inferior to the optic nerve to over the nerve and even on the macula. The reflex
      disappeared when the air infusion was stopped and reappeared when the air
      infusion resumed. CONCLUSION: Air infusion forces are directed on to the surface
      of the retina and these forces might damage the retina resulting in post
      vitrectomy scotomas.

PMID- 25390987
TI  - Clinical and genetic heterogeneity of crystalline retinopathies: report of two
      families without bietti crystalline dystrophy.
AB  - PURPOSE: To report variations in the inheritance pattern and clinical
      presentation of crystalline retinopathies. METHODS: Two different families with
      crystalline retinopathy were studied with a complete family history and
      ophthalmologic examination including Goldmann kinetic perimetry and
      electroretinography. Genetic studies were performed in one of the families.
      RESULTS: One of the families had a clearly autosomal dominant mode of inheritance
      while the other family most likely follows an autosomal recessive pattern.
      Several members in each family had significant retinal pigment epithelial
      atrophy, intraretinal crystals, relatively pink optic nerves, and paracentral
      visual field defects, all of which are clinical features resembling those of
      Bietti crystalline retinopathy. Examination of peripheral leukocytes using
      transmission electron microscopy in selected affected members showed no evidence
      of classical lysosomal crystals that are characteristics for Bietti crystalline
      retinopathy. No pathogenic mutations were identified in the CYP4V2 gene.
      CONCLUSIONS: Not all crystalline retinopathies are Bietti's. Further genetic,
      biochemical, and pathologic studies are required to better differentiate between
      these retinopathies.

PMID- 25390988
TI  - Optical coherence tomographic findings in bietti's crystalline tapetoretinal
      dystrophy.
AB  - PURPOSE: To report the optical coherence tomography (OCT) findings of Bietti
      crystalline tapetoretinal dystrophy. DESIGN: Observational case report. METHODS:
      A subject with Bietti crystalline tapetoretinal dystrophy was evaluated with
      ophthalmoscopy, fluorescein angiography, and OCT (Stratus). RESULTS: OCT showed
      thinning and hyporeflectivity of the outer nuclear layer in the macula due to
      photoreceptor degeneration. The retinal areas showing atrophy of the retinal
      pigment epithelium displayed greater penetration of the optical beam into the
      choroid and visualization of residual choroidal vessels. The hyperreflective band
      normally seen under the neurosensory retina was extremely wide when atrophy of
      the entire retinal pigment epithelium/choriocapillaris complex was found. Above
      this band, and within the neurosensory retina, some hyperreflective dot-like
      lesions were seen that could be related to crystals. CONCLUSIONS: In cases of
      Bietti crystalline tapetoretinal dystrophy, OCT shows changes secondary to fundus
      atrophy and more specific changes that can be related to the presence of
      crystals, thereby making OCT particularly useful for demonstrating macular
      atrophic abnormalities.

PMID- 25390989
TI  - Parafoveolar intraretinal crystals in pearson syndrome.
AB  - PURPOSE: To describe the occurrence of bilateral parafoveolar intraretinal
      crystals in a patient with Pearson syndrome (bone marrow-pancreas syndrome).
      METHODS: A patient with an established diagnosis of Pearson syndrome underwent
      complete ophthalmic examination and optical coherence tomography. RESULTS: Fine,
      refractile, crystalline, parafoveolar intraretinal deposits were seen
      bilaterally. There was no evidence of pigmentary retinopathy or ophthalmoplegia.
      CONCLUSIONS: Intraretinal crystals in the macula may be seen in Pearson syndrome
      and may not cause a substantial decrease in visual acuity. Pearson syndrome
      should be considered in the differential diagnosis of parafoveolar crystalline
      retinopathy.

PMID- 25390990
TI  - Optical coherence tomography reveals retinal degeneration from persistent
      submacular fluid after pneumatic retinopexy for rhegmatogenous retinal
      detachment.
AB  - PURPOSE: To report a case of retinal degeneration associated with long-standing
      submacular fluid. METHODS: Observational case report. RESULTS: A 64-year-old
      African American woman with hand motion vision was found to have a macula
      involving rhegmatogenous retinal detachment (RRD). Following an otherwise
      successful repair by pneumatic retinopexy, a small puddle of subretinal fluid
      persisted in the macula, limiting her vision to 20/70 at 1 month's time. Refusing
      further intervention, she experienced visual decline to 20/200 2 months
      postoperatively due to retinal degeneration seen as progressive retinal thinning
      and irregularity of the outer neurosensory retina on optical coherence
      tomography. CONCLUSION: Although the literature suggests that submacular fluid
      following RRD repair by scleral buckle does not affect visual acuity, persistent
      submacular fluid may result in progressive retinal degeneration with concomitant
      vision loss as early as 2 months following repair.

PMID- 25390991
TI  - Surgical evacuation of submacular exudates secondary to a vasoproliferative tumor
      of the retina.
AB  - PURPOSE: To report a case demonstrating excellent visual recovery following
      surgical removal of subfoveal exudation secondary to a vasoproliferative tumor of
      the retina (VPTR). DESIGN: Observational case report. METHODS: Review of medical
      records. RESULTS: A 39-year-old man presented with decreased vision secondary to
      subfoveal exudation from a VPTR. The tumor was successfully treated with
      cryoretinopexy, but the hard exudates that had formed in under the fovea
      remained. There was no change in vision for 18 months following the
      cryoretinopexy. A decision was made to surgically remove the exudates using
      similar techniques to those presented in the literature for diabetic exudation.
      Over the next several weeks the patients vision recovered to the 20/25 level and
      has remained this way for 5 years. CONCLUSIONS: Patients with subfoveal exudates
      secondary to VPTR may benefit from subretinal surgery to remove the exudates.

PMID- 25390992
TI  - Late reopening of spontaneously closed traumatic macular hole.
AB  - PURPOSE: To describe a case of a late reopening of a traumatic macular hole (MH)
      2 years after initial spontaneous closure. METHODS: A 12-year-old boy was hit by
      a softball in the right eye, with an immediate decrease of visual acuity (20/100
      in the right eye). He presented MH in the right eye. RESULTS: Without surgical
      intervention, the traumatic MH closed spontaneously 2 weeks later, with visual
      recovery (20/50 in the right eye). Two years later, the MH reopened, with visual
      loss (20/70 in the right eye) but no sign of posterior vitreous detachment or
      epiretinal membrane. Spontaneous closure did not occur, and the patient underwent
      vitrectomy with internal limiting membrane peeling and SF6 gas tamponade. The MH
      closed after surgery, and visual acuity improved (20/40 in the right eye).
      CONCLUSIONS: While reopening might be a rare complication, ophthalmologists
      should be aware of it occurring as a possible late complication of a
      spontaneously closed traumatic MH.

PMID- 25390993
TI  - Bilateral vasoproliferative retinal tumors in a patient with autosomal dominant
      aniridia.
AB  - PURPOSE: To document retinal vasoproliferative tumors in a patient with aniridia.
      METHODS: A 32-year-old woman with known autosomal dominant aniridia and lifelong
      visual acuity of approximately 20/80 noted further visual acuity loss. RESULTS:
      Examination revealed horizontal nystagmus and visual acuity of 20/100 in both
      eyes. Both eyes displayed a narrow rim of rudimentary iris with visualization of
      the entire lens and zonule. The cornea was clear and minimal posterior
      subcapsular cataract was noted. Both eyes showed diffuse retinal pigment
      epithelial alterations. The fovea was flat and without depression on optical
      coherence tomography. Inferiorly in both eyes was exudative retinal detachment
      from ill-defined vascular retinal tumors of approximately 15 mm diameter and 3.5
      mm thickness. Both eyes were treated with plaque radiotherapy. CONCLUSIONS:
      Although aniridia typically affects the anterior segment of the eye, vision
      threatening retinal detachment from vasoproliferative tumor can occur.

PMID- 25390994
TI  - Choroidal metastasis from carcinoma of the bladder.
AB  - PURPOSE: To report choroidal metastasis from the newly described nested variant
      of urothelial carcinoma of the bladder as the initial presentation of metastatic
      disease. METHODS: A 58-year-old man with a history of urothelial bladder
      carcinoma developed progressive decreased visual acuity in the right eye. Fundus
      examination showed an amelanotic choroidal tumor simulating a choroidal melanoma.
      Results of ancillary diagnostic tests, needle aspiration biopsy, and systemic
      workup failed to confirm the diagnosis of choroidal metastasis. The patient was
      treated with enucleation the affected right eye. RESULTS: Histopathologic
      analysis of the enucleated eye disclosed a choroidal metastatic carcinoma with
      urothelial features similar to those of the bladder carcinoma excised previously.
      Despite adjuvant systemic chemotherapy, the patient died 7 months after
      enucleation. CONCLUSION: Choroidal metastasis may be the initial manifestation of
      metastatic bladder carcinoma and is associated with a poor survival prognosis.

PMID- 25390995
TI  - Angioid streaks in a patient with hemochromatosis and secondary porphyria cutanea
      tarda.
AB  - PURPOSE: To present the clinical findings in a patient with hemochromatosis,
      secondary porphyria cutanea tarda and angioid-like streaks. METHODS:
      Retrospective clinical report. RESULTS: This patient presented with angioid like
      streaks and choroidal neovascularization. Hemochromatosis is a common genetic
      disease in the general population and presents at variable ages. The iron
      deposition may predispose to angioid streaks. In addition, secondary porphyria
      cutanea tarda (PCT) is associated with hemochromatosis and care should be taken
      during intraocular surgery since PCT may predispose to phototoxcity. CONCLUSION:
      In patients with angioid-like streaks, there should be consideration of
      hemochromatosis as a possible cause.

PMID- 25390996
TI  - Histology of retina overlying bacterial subretinal abscess and implications for
      treatment.
AB  - PURPOSE: To evaluate the state of the retina overlying a subretinal abscess and
      its contents by histopathologic analysis and electron microscopy (EM) and to
      determine implications for treatment. METHODS: Case report of a patient with a
      subretinal abscess secondary to Klebsiella pneumoniae infection who underwent
      pars plana vitrectomy, PPL, endolaser, retinectomy, abscess drainage, and retinal
      biopsy. The retinal biopsy was analyzed histologically using special stains, and
      EM of the abscess contents was performed. RESULTS: Postoperatively, the retina
      remained attached, and the patient regained visual acuity of 20/60. Culture of
      the vitrectomy specimen yielded K. pneumoniae. Retinal biopsy revealed a
      partially intact inner retina with destruction of the outer retinal layers in the
      setting of acute inflammation. Results of gram, Grocott-Gomori methenamine-silver
      nitrate, and acid-fast staining of the retinal biopsy specimen were negative. EM
      of the abscess contents revealed cellular debris with scattered inflammatory
      cells but no bacteria. CONCLUSION: This case demonstrates that aggressive
      surgical management of a subretinal abscess due to K. pneumoniae in an eye can
      result in useful vision. Management included retinectomy of the retina overlying
      the abscess that revealed photoreceptor destruction with intraretinal
      inflammation. Drainage of a subretinal abscess without removal of the overlying
      retina may limit treatment effectiveness and spare retina that is not functional.

PMID- 25390997
TI  - Etanercept monotherapy induces complete resolution of cystoid macular edema in a
      patient with intermediate uveitis.
AB  - BACKGROUND: There is controversy on whether etanercept, an anti-tissue necrosis
      factor agent, shares infliximab's purported efficacy in the treatment of
      intermediate uveitis and, in particular, intermediate uveitis-associated cystoid
      macular edema. METHODS: Interventional case report. RESULTS: A 29-year-old
      patient with decreased vision bilaterally secondary to cystoid macular edema
      complicating chronic idiopathic intermediate uveitis refractory to oral
      corticosteroids, methotrexate (17.5 mg weekly), and cyclosporine (100 mg daily)
      started etanercept monotherapy with rapid and complete resolution of cystoid
      macular edema and dramatic improvement in visual acuity. CONCLUSION: Etanercept
      may have a role in the treatment of refractory intermediate uveitis and
      intermediate uveitis-associated cystoid macular edema.

PMID- 25390998
TI  - Macular degeneration in a Japanese patient with aceruloplasminemia.
AB  - PURPOSE: To characterize the clinical features of a Japanese patient with macular
      degeneration in aceruloplasminemia. METHODS: The clinical features were evaluated
      by visual acuity measurements, fluorescein angiography, electroretinography, and
      kinetic visual field testing. RESULTS: We observed a Japanese patient with
      macular degeneration in aceruloplasminemia. This patient also had diabetes
      mellitus and neurodegeneration. Ocular examination showed macular degeneration,
      which included yellow deposits around the macula area and no foveal reflex.
      CONCLUSION: It has been reported that Japanese patients with aceruloplasminemia
      have atrophy of the retinal pigment epithelium in the midperipheral area and
      yellowish discoloration of the fundus. However, the retinal findings and results
      of fluorescein angiography in our case were very similar to those for a white
      patient. We suggest that retinal degenerations in Japanese patients with
      aceruloplasminemia have clinical variability. We believe that impairment of iron
      metabolism caused by iron overload in the retina led to retinal degeneration in
      this case.

PMID- 25390999
TI  - Morphologic and functional changes in solar retinopathy: a study by optical
      coherence tomography and fundus-related perimetry.
AB  - PURPOSE: Solar retinopathy is caused by macular exposure to solar radiation and
      is mediated by photochemical and thermal mechanisms. Ultrastructural examination
      shows the retinal pigment epithelium (RPE) and the outer segments of the
      photoreceptors as the most susceptible to solar insult. The authors describe the
      optical coherence tomography (OCT-3 Stratus) and the fundus-related perimetry (MP
      1 microperimeter) findings of the disease. METHODS: The authors performed a
      complete ophthalmologic examination in three patients with solar retinopathy,
      including two new, highly sensitive diagnostic tools, the OCT-3 and the MP-1,
      soon after solar exposure and again up to 18 months after diagnosis. RESULTS:
      Symptoms and macular changes were similar in these three patients despite
      different exposures to solar radiation. On initial visit, the OCT scans revealed
      in all three patients an irregular inner high-reflective layer (I-HRL) that
      appeared fragmented and interrupted. In addition, the OCT images showed a
      hyperreflective lesion, which, in one patient, involved the full foveal
      thickness, and in two patients was confined to the outer half of the foveal
      layers. In two patients there was an associated reduced reflectiveness of the
      outer high-reflective layer (O-HRL). These OCT signs disappeared as early as 1
      month follow-up. Fundus-related perimetry demonstrated, at the first visit, a
      significant reduction of retinal sensitivity in all patients, which was no longer
      evident at 1-month follow-up. CONCLUSIONS: OCT may be an effective tool in
      diagnosing the acute phase of solar retinopathy and in differentiating it from
      other maculopathies. Fundus-related perimetry would seem to be a useful
      adjunctive method to better characterize the functional aspect of the disease.

PMID- 25391000
TI  - Focal retinal pigment epithelium breaks in central serous chorioretinopathy.
AB  - PURPOSE: To describe new evidence supporting a theory on the etiology of the
      focal retinal pigment epithelium (RPE) leak in central serous chorioretinopathy
      (CSC). METHODS: The records of two patients with CSC were reviewed, including
      examination details and results of fluorescein angiography, fundus
      autofluorescence imaging, and optical coherence tomography (OCT). RESULTS: A
      defect in the RPE monolayer demonstrated with OCT that corresponded to the site
      of the focal leak shown by fluorescein angiography was found in both patients.
      CONCLUSION: The focal leak shown by fluorescein angiography in patients with
      active CSC is caused by an RPE defect in at least some cases. This finding
      supports a previously reported theory on the pathogenesis of CSC.

PMID- 25391001
TI  - Bilateral serous macular detachment in a woman on sildenafil for pulmonary
      hypertension.
AB  - PURPOSE: To report a case of bilateral serous macular detachment in a woman on
      sildenafil for pulmonary hypertension. METHODS: Case report of a 52-year-old
      woman presenting with painless loss of vision bilaterally after starting
      sildenafil 1 month earlier for pulmonary hypertension. RESULTS: Bilateral serous
      macular detachment with cystoid macular edema was noted on funduscopy and optical
      coherence tomography (OCT). Fluorescein angiography showed several pinpoint areas
      of faint leakage with pooling in late views. Vision subjectively normalized 1
      week after discontinuing sildenafil. Funduscopy and OCT also normalized on follow
      up examination. CONCLUSION: Bilateral serous macular detachment can be associated
      with sildenafil use for pulmonary hypertension. Vision loss is reversible with
      prompt discontinuation of the drug.

PMID- 25391002
TI  - Ageing individuals and ageing populations.
AB  - Public health problems associated with ageing, due to its complexity, enters the
      spheres of interests in many fields: demography, economics, and politics. In many
      countries challenges related to the increasing number of people at retirement age
      remain strongly dependent on the actual and projected numbers of people at
      productive age emerging from the demographic condition of the population. The
      article addresses the complexity of the relations between life expectancy,
      healthy life expectancy and the length of life in disability. Underlined are the
      social and economic conditions of life in the period of the old age, including
      the problem of inequalities in health and the role of research in the field of
      public health for the proper recognition of the problem and rational planning of
      resource allocation and organizational measures aimed at meeting social
      expectations associated with ageing.

PMID- 25391003
TI  - Measles outbreak registered by the District Sanitary-Epidemiological Station in
      Czestochowa in 2013.
AB  - INTRODUCTION: Since 2001, Poland has been committed to measles elimination
      programme coordinated by the World Health Organization. This programme is
      intended to sustain 95% coverage with measles vaccines and ensure laboratory
      confirmation of suspected measles cases. In 2013, a total of 89 measles cases
      were reported in Poland. Of them, 14 cases were notified to the District Sanitary
      Epidemiological Station (DSES) in Czestochowa. PURPOSE. The purpose of this study
      was to evaluate the epidemiological situation of measles in Czestochowa with
      focus on the increase in measles incidence observed in the second quarter of
      2013. MATERIAL AND METHODS: To analyze the epidemiological situation of measles,
      the reports on the cases of infectious diseases and poisonings in Poland in 2000
      2013 (MZ-56) from the National Institute of Public Health-National Institute of
      Hygiene (NIPH-NIH) and Czestochowa DSES were employed. The analysis of
      immunization coverage of children and adolescents in selected year groups in 2009
      2012 was performed using the data retrieved from annual reports issued by
      Czestochowa DSES (MZ-54). RESULTS: In 2000-2012, three cases of measles were
      notified to Czestochowa DSES. Of them, two cases and one case were reported in
      2003 and 2011, respectively. In 2013, an increase in the number of measles cases
      and measles incidence was observed. A total of 14 adult cases, aged 22-38 years,
      were reported and the incidence was 3.78 per 100,000. Of them, 13 cases were
      males (93% of the total). The infection affected 8 inmates of the Day Care Centre
      in Czestochowa, 2 individuals who lived near this institution and 4 individuals
      who were not epidemiologically linked to the outbreak. Of the cases, 12
      individuals were hospitalized, i.e. 86% of all cases. Of 14 reported cases, only
      one individual had a history of measles vaccination. CONCLUSIONS: Measles remains
      a highly infectious disease which can be easily transmitted in the unvaccinated
      population.

PMID- 25391004
TI  - Seroprevalence of measles-specific antibodies in the group predominantly affected
      by measles in 2006-2009 in Poland.
AB  - INTRODUCTION: Irrespective of the high vaccination coverage against measles,
      sporadic measles outbreaks still occur in Poland. In 2006-2009, a slight increase
      in the number of measles cases was observed. Of these cases, people born in 1976
      198 9 were predominantly affected. AIM: The aim of the study was to evaluate the
      immunity to measles in the aforesaid age group. MATERIAL AND METHODS: The serum
      samples were selected from the serum bank in which material collected from the
      general population living in 5 provinces in Poland is stored. These samples were
      collected from patients hospitalized due to emergencies in 2010-2011. The
      antibody titre against measles was determined in each serum sample by ELISA test
      (Genzyme Virotech). Linear regression models using log-transformed antibody
      titres were used to compare the values. RESULTS: The serum samples collected from
      483 persons, including 111 females and 372 males were tested. All patients had
      antibody titres exceeding 0.5 IU/ml. The antibody titre was statistically
      significantly associated with the vaccination coverage in each age group in
      particular province. CONCLUSIONS: The results of this study suggest good immunity
      to measles in the general population in Poland. The disparities between randomly
      selected provinces demonstrated a relation with the coverage rates as well as the
      differences in measles incidence which is observed recently between these
      provinces.

PMID- 25391005
TI  - Ulceroglandular tularemia complicated by pneumonia--a case report.
AB  - Tularemia is an antropozoonosis caused by Gram-negative coccobacillus Francisella
      tularensis. The majority of tularemia cases are reported in summer due to
      exposure to insect and tick bites. This paper discusses a case of 11-year-old boy
      diagnosed with ulceroglandular tularemia complicated by pneumonia. CONCLUSIONS:
      tularemia should be considered in differential diagnosis of febrile condition and
      lymphadenopathy in children who contracted disease in summer or autumn,
      especially if there is a history of insect or tick bite.

PMID- 25391006
TI  - Ribavirin priming has no beneficial effects for chronic hepatitis C patients.
AB  - AIM: The aim of this study is to assess the efficacy of an initial dose of
      ribavirin administered before a 48-week course of treatment with peg-IFN +
      ribavirin in treatment-naive patients and in patients after previous failure of
      CHC treatment. MATERIAL AND METHODS: A total of 103 patients with chronic
      hepatitis C infected with genotype 1 HCV were qualified to the study. Study
      patients were randomised to receive one of two treatments: A- RBV for 4 weeks
      followed by combined therapy with peg-IFN alpha-2a +RBV for 48 weeks (n = 73), or
      B- combined therapy with peg-IFN alpha-2a +RBV for 48 weeks (n = 30). RESULTS:
      SVR 24 was observed in 44% patients in group A and in group 40% patients in group
      B (40%), p > 0.05. Comparing subgroups of the naive patients, it was found that
      the SVR24 value was higher in group A than group B (57% vs. 47%, p > 0.05). In
      the re-therapy subgroups, higher treatment response rates in patients not
      responding earlier was found in group A than group B (39% vs. 16%, p > 0.05).
      CONCLUSION: No significant advantage was found in the use of a priming method
      over a standard regimen. However, it could be recommended in patients with a
      total lack of response to peg-IFN and ribavirin when no other therapeutic options
      are available.

PMID- 25391007
TI  - Outpatient use of systemic antibiotics in Poland: 2004-2008.
AB  - OBJECTIVES: The goal of this study was to evaluate the quantity and pattern of
      outpatient antibiotic use in Poland between 2004 and 2008 and to determine the
      trends in prescribing practice. To investigate the oral and parenteral outpatient
      antibiotic use in Poland. MATERIAL AND METHODS: Data concerning outpatient use of
      systemic antibiotics between 2004 and 2008 were obtained from Polish National
      Health Fund databases expressed as the number of defined daily doses (DDD) per
      1000 inhabitants per day (DID) according to the international Anatomical
      Therapeutic Chemical ATC classification system of the World Health Organization
      (WHO, version 2009). RESULTS: Total outpatient antibiotic use in Poland varied
      from the lowest 17.88DID in 2004 to the highest 21.39DID in 2007. Penicillins
      (J01C) represented the most frequently prescribed antibiotics constituting more
      than 50% of the total outpatient antibiotic use. The other most popular groups of
      antibiotics were tetracyclines (J01A), macrolides (J01F). On the fourth and fifth
      position were cephalosporins (J01D) and quinolones (J01M), respectively. The
      parenteral antibiotic use did not exceed 1% of the total outpatient antibiotics
      prescribed with cefuroxime being the most frequently prescribed drug.
      CONCLUSIONS: Total outpatient use of antibiotics in Poland in 2004-2008 was
      comparable to the median European level. The consumption of all antibiotics
      slightly increased from 2004 to 2007, and decreased in 2008. The most often
      prescribed antibiotics were penicillins, mainly amoxicillin and amoxicillin with
      enzyme inhibitor. During the study period the use of the older (narrow-spectrum)
      antibiotics decreased in favour of the newer (broad-spectrum) antibiotics. The
      results suggest the discrepancy between national recommendations and choice of
      antibiotics by physicians.

PMID- 25391008
TI  - Alert microorganisms isolated from patients hospitalized in Malopolskie province
      in 2010-2012.
AB  - OBJECTIVE: Healthcare centers undertake supervisory activities to control health
      care-associated infections (HCAIs) by elaborating procedures, identifying alert
      microorganisms and analyzing data collected. The aim of the study was to analyze
      the prevalence of alert microorganisms in hospital wards in 2010-2012. MATERIAL
      AND METHODS: Legislation which is in force since several years introduced the
      principles of health care-associated infections control and reporting system.
      Analysis was based on annual reports on alert microorganisms provided by 19
      District Sanitary and Epidemiological Stations from Malopolskie province. The
      data discuss positive tests results for alert microorganisms in patients who
      stayed in hospitals supervised by the Sanitary and Epidemiological Stations.
      RESULTS: Compared to 2010-2011, the number of tests per hospital bed in 2012 was
      lower, amounting to 24 (2010 - 44, 2011 - 34). Of these tests, the majority was
      performed in the following wards: transplantology (2010 - 339, 2011 - 354, 2012 -
      330), burn care (2010 - 354, 2011 - 148, 2012 - 113) and ICUs for adults (2010 -
      155, 2011 - 157, 2012 - 140). In 2010-2012, an increase in the number of positive
      test results for extended-spectrum beta-lactamase-producing Enterobacteriaceae
      (ESBL+) and Clostridium difficile as well as slight decrease in the number of
      positive test results for other alert microorganisms were noted. The highest
      number of microorganisms was identified in neonatal and neonatal pathology
      (Enterobacteriaceae ESBL+); pediatric and infectious diseases (Rotavirus);
      infectious diseases (Rotavirus, C.difficile); burn care (Acinetobacter baumanii,
      Pseudomonas sp.) and ophthalmic and hemodialysis wards (MRSA). CONCLUSION:
      Irrespective of a decrease in the number of tests per hospital bed in 2012, a
      high number of positive test results for alert microorganisms was observed. It
      suggests the necessity for wider application of collected data as to improve
      monitoring of infections and reduce resulting threats.

PMID- 25391009
TI  - Sensitivity of passive diarrhea surveillance in infants up to the second year of
      life in Malopolskie voivodeship.
AB  - INTRODUCTION: In EU countries and also in Poland, the surveillance of infectious
      acute gastro-enteritis is a mandatory system based on cases notification
      (suspected and confirm) conducted by physicians in hospitals and ambulatory care.
      STUDY OBJECTIVE: The assessment of surveillance sensitivity on acute diarrhea in
      children up to 2nd year of life in Malopolskie voivodeship from 2009 to 2012.
      MATERIAL AND METHODS: The data about 720 infants surveyed respectively from birth
      up to 2nd year of life were used in this study. The information on acute diarrhea
      cases (outpatient and hospitalized) occurred in infants during follow-up was
      included in analysis. The data derived from medical records. Each case of acute
      diarrhea in infants detected by medical records was surveyed in local
      surveillance system on infectious diseases whether it was notified by physician.
      RESULTS: The surveillance sensitivity on acute diarrhea in infants up to 2nd year
      of life increased in Malopolskie voivodeship from 14.3% in 2009 to 24.3% in 2012.
      The sensitivity of surveillance on hospitalized cases was twofold higher compared
      to all kind of cases assessed inclusively. CONCLUSION: The surveillance
      sensitivity on acute diarrhea in infants up to 2nd year of life improved
      significantly in recent years but is still too low, especially with respect to
      outpatient cases.

PMID- 25391010
TI  - Influenza in Poland in 2011-2012 and in 2011/2012 and 2012/2013 epidemic seasons.
AB  - This paper aimed at evaluating the epidemiological situation of influenza in
      Poland in 2011-2012 and in 2011/2012 and 2012/2013 epidemic seasons and comparing
      it with the situation observed in the previous years. MATERIAL AND METHODS: An
      analysis was mainly based on three sources of data: (1) bulletins "Infectious
      diseases and poisonings in Poland in 2012" and "Vaccinations in Poland in 2012"
      (NIPH-NIH, CSI. Warsaw 2013) and analogically former bulletins, (2) "Reports on
      influenza cases and persons suspected of influenza", sent in 2013 and previous
      years to the Department of Epidemiology, NIPH-NIH by the Voivodeship Sanitary-
      Epidemiological Stations, (3) data of the Department of Influenza Research,
      National Influenza Centre, NIPH- NIH - results of virological testing performed
      in 2011/2012 and 2012/2013 epidemic seasons in the National Influenza Centre
      and/or laboratories of the Voivodeship Sanitary-Epidemiological Stations (VSES)
      within influenza surveillance - Sentinel as well as beyond this system. Data on
      influenza cases come from aggregated notifications which are sent obligatorily to
      the VSES by all health care units and physician practices. Influenza, influenza
      like illness and acute respiratory infections, i.e. cases meeting the criteria
      recommended in influenza surveillance in the European Union are subject to
      mandatory notification. RESULTS: In 2011-2012, there was an increase in the
      number of influenza and influenza-like illness cases in Poland compared to 2010,
      i.e. 2- and 2,5-fold, respectively. In 2011, a total of 1 156 357 cases were
      reported and incidence amounted to 3 001.5 per 100,000 population (11 014.5 in
      age group 0-4 years). As many as 0.51% of infected persons were referred to
      hospital. According to the CSO data, 95 fatal cases of influenza were notified.
      Influenza vaccination coverage was 2.8%. In 2012, 1 460 037 cases were registered
      and incidence was 3 789.0 (17 807,1 in age group 0-4 years). A total of 0.33% of
      influenza cases were referred to hospital. As many as 4 deaths due to influenza
      were reported. Percentage of population vaccinated against influenza amounted to
      2.3%. In 2011/12 epidemic season, 1 085 471 cases were noted and incidence was 2
      816.6 per 100,000 population (12 792.3 in age group 0-4 years) while in 2012/13
      epidemic season its number was nearly 3-fold higher, i.e. 3 025 258 cases and
      incidence - 7 851.0 (30 591.7 in age group 0-4 years). In both epidemic seasons,
      type A influenza subtype H1N1 and human respiratory syncytial virus (RSV)
      predominated in infections with influenza virus and other viral respiratory
      infections, respectively. Antigenic analysis of influenza strains showed their
      affinity with vaccine strains of the vaccines recommended for these epidemic
      seasons. SUMMARY: An increase in the number of notified cases of influenza and
      influenza-like illness, which is recently observed in Poland, is significantly
      affected by the improving quality (especially sensitivity) of surveillance
      system, commenced in the 2009 influenza pandemic. This surveillance system,
      however, is still not sufficiently uniform and stable. Low percentage of
      population vaccinated against influenza suggests the ineffectiveness of influenza
      vaccine promotion campaigns conducted so far. An increase in the influenza
      vaccination coverage to the average observed in the EU countries should be one of
      the priorities for the sanitary-epidemiological stations.

PMID- 25391011
TI  - Rabies in Poland in 2012.
AB  - OBJECTIVE: Evaluation of the epidemiological situation of rabies in Poland in
      2012. MATERIAL AND METHODS: Evaluation was based on the analysis of data from
      questionnaires sent by the Epidemiological-Sanitary Stations. The data are from
      questionnaires of persons who were administered vaccine against rabies following
      exposure in Poland and beyond its territory and data from annual bulletin
      "Infectious diseases and poisonings in Poland in 2012"(Czarkowski MP et al.,
      Warsaw, NIH and CSI) and epizootic data provided by the General Veterinary
      Inspectorate. RESULTS: In 2012, a total of 257 animal rabies cases were
      registered in Poland, i.e. nearly 60% more compared to 2011. More than 83% of
      these cases were reported in Podkarpackie province. Compared to 2011, more than
      3.5 increase was noted there. One rabid dog was reported in Slaskie province
      where one rabies infection in fox was noted there a year ago. Rabies infections
      in terrestrial animals were also reported in the following provinces:
      Malopolskie, Lubelskie, Warminsko-mazurskie and Podlaskie. Single rabies
      infections in bats were registered in other regions of Poland. In 2012, a total
      of 7,753 persons were vaccinated against rabies, including 315, i.e. more than 4%
      due to the exposure to animals infected with rabies virus. Of persons vaccinated
      due to contact with a rabid animal, nearly 40% and more than 44% were vaccinated
      following contact with rabid fox and domestic animal, respectively. As with the
      previous years, humans were vaccinated mostly due to contact with dogs and cats
      in which rabies could not be excluded - 5,974 persons (77%). CONCLUSIONS: A
      reason for concern is an increase in the number of animal rabies cases reported
      in 2012, especially in Podkarpackie province. Epizootic situation in Poland
      affects slightly the number of persons vaccinated against rabies who had contact
      with an animal which potentially is a source of rabies virus. Since many years,
      this number remains stable, amounting to 7-8,000 annually.

PMID- 25391012
TI  - Sick people and sick populations--legacy of Geoffrey Rose.
AB  - Developed by Geoffrey Rose strategy of preventive medicine caused a major
      breakthrough in thinking about the effectiveness of preventive measures. The
      distinction between actions within the high-risk groups against activities at the
      level of the whole population raised awareness of public health workers that
      focus on highly vulnerable individuals may lead to underestimation of the problem
      of cases among individuals out high risk groups, who due to their numbers in the
      population, participate to a greater number of cases. The author of this study
      points to the importance of this distinctions, but also highlights some
      methodological problems of Rose theory. It is postulated efficiency-oriented
      approach to prevention that takes into account integrated action which includes
      activities at the level of the whole population, but also an attempt to deliver
      individualized messages to smaller groups and ant to individuals including those
      beyond high-risk groups. In the author's opinion this is of particular importance
      in the context of strong social stratification.

PMID- 25391013
TI  - Occupational activity and health of Warsaw inhabitants. Part I. Unemployment: a
      preliminary analysis.
AB  - BACKGROUND: The health deterioration of the unemployed is the serious challenge
      for the public health, especially of that health promotion programs for this
      group were not always effective. OBJECTIVES: The aim of the papers is to
      recognise initially the health effects of unemployment among Warsaw inhabitants
      in order to formulate recommendations for future more comprehensive research.
      MATERIAL AND METHODS: Out of the respondents who joint the program of social
      participation in health reforms, 23 the unemployed and 172 employed persons were
      included to the study. The eight indicators of health status and eight components
      of health security were assumed. RESULTS: As regards health status, compared to
      employed persons, relatively more of the unemployed perceived their health,
      physical and mental well-being as worse, they more frequently remained at home
      due to illness and were admitted to hospital, but relatively fewer of them
      visited physicians. As regards health security, relatively more the unemployed
      assessed their medical expenses as very high, used only public health care and
      well understood the information received from family doctor, but relatively fewer
      of them experiences difficulties in getting to physicians. The future retirement
      system they perceived dramatically poorly. However, not all visible differences
      reached the level of statistical significance. CONCLUSIONS: Despite the
      limitation of our findings due to a preliminary nature of the study, they
      confirmed unquestionable relationship between unemployment and health
      deterioration. The recommendations for future more extensive research were
      presented in detail.

PMID- 25391014
TI  - Occupational activity and health of Warsaw inhabitants. Part II. Work in
      retirement age: a preliminary analysis.
AB  - INTRODUCTION: In the situation of rapid population ageing, it is necessary to
      encourage the older people to work longer. This requires a recognition of health
      conditions that cause the decision to continue working in retirement age.
      OBJECTIVES: The aim of the study was to determine differences in health status
      and health security between working and non-working retirees involved in the
      program of social participation in healthcare reform. MATERIAL AND METHODS. Of
      406 participants of the program of social participation in healthcare reform, 161
      non-working retirees and 21 working retirees were involved to analysis. Eight
      indicators of health status and eight components of health security were adopted.
      RESULTS: Our findings showed the weak relationship between health and the working
      continue in retirement age. The considerable differences between the groups were
      reported only for physical well-being; the working retirees felt better. They
      continued work despite the fact that most of them perceived their health poorly
      and almost all suffered from chronic diseases. The working in retirement age was
      related with financial and social benefits to a greater extent. The working
      retirees rarely reported financial problems, the medical expanses was less
      onerous for them, they had the great opportunity to use the private physician
      services, and they more often perceived social support. The negative effect of
      working in retirement age, however, was related with the lack of time to rest,
      more negative assessment of existing healthcare system and less satisfaction with
      health information received from family doctor. CONCLUSIONS: Our finding would
      indicate that health status influences the work in retirement age to a limited
      extend. Financial motivation and social factors seems to be the main determinants
      of working continue. The recommendations for future more extensive research were
      presented in detail.

PMID- 25391015
TI  - Accidental drownings in Poland in 2000-2012.
AB  - OBJECTIVE: Drowning is a public health problem which is poorly recognized and
      analyzed in the Polish literature so far. MATERIAL AND METHODS: We analyzed all
      available sources of information on drowning in Poland, i.e. the data of the
      Central Statistical Office (causes of deaths, accidents at work) and Police
      Headquarters (circumstances of drowning). We discussed changes in drowning
      frequency, analyzing both time and space perspective as well as demographic
      profiles of fatal drowning cases. RESULTS: In 2000-2012, an estimated 12,702
      persons died due to drowning in Poland (median of crude mortality rate - 2.6 per
      100,000 population). Mortality due to drowning was on downward trend. Males aged
      45-59 years, especially with vocational education, were at the highest risk of
      drowning. In the period analyzed, the highest and the lowest mortality rates were
      reported in Warminsko-mazurskie (median of mortality rate - 4.7) and Slaskie
      voivodships (median of mortality rate - 1.2), respectively. The highest drowning
      frequency was noted in the period from June to August in which a total of 5,981
      cases were registered, i.e. 47.1% of all recorded drownings. CONCLUSIONS: A risk
      of death due to drowning in Poland is higher compared to the average in other EU
      countries. There is a necessity for public health intervention in this field.
      Furthermore, reporting systems regarding drowning in Poland should be unified.

PMID- 25391016
TI  - Tea and health--a review of the current state of knowledge.
AB  - Until recently, tea has been numbered among stimulants, i.e. products of no
      nutritional value. Nowadays, with advance of research studies, the amount of data
      suggesting beneficial effect of tea on health is increasing. Polyphenols are the
      basic tea ingredients to which positive effect on human body is attributed. Their
      wide spectrum of biochemical activity, including a strong antioxidant potential,
      contributes to the situation in which tea may have various beneficial functions
      in the body. Research studies focus mostly on green tea which is believed to
      reduce the risk of many modern diseases. However, so far the preventive effect of
      tea has not been confirmed yet. Despite it being a natural product, too much tea
      in a diet carries the risk of excessive caffeine intake and decreased absorption
      of non-heme iron which may be of detrimental consequences for some groups of
      consumers.

PMID- 25391018
TI  - Activation of innate immune-response genes in little brown bats (Myotis
      lucifugus) infected with the fungus Pseudogymnoascus destructans.
AB  - Recently bats have been associated with the emergence of diseases, both as
      reservoirs for several new viral diseases in humans and other animals and, in the
      northern Americas, as hosts for a devastating fungal disease that threatens to
      drive several bat species to regional extinction. However, despite these
      catastrophic events little Information is available on bat defences or how they
      interact with their pathogens. Even less is known about the response of bats to
      infection during torpor or long-term hibernation. Using tissue samples collected
      at the termination of an experiment to explore the pathogenesis of White Nose
      Syndrome in Little Brown Bats, we determined if hibernating bats infected with
      the fungus Pseudogymnoascus destructans could respond to infection by activating
      genes responsible for innate immune and stress responses. Lesions due to fungal
      infection and, in some cases, secondary bacterial infections, were restricted to
      the skin. However, we were unable to obtain sufficient amounts of RNA from these
      sites. We therefore examined lungs for response at an epithelial surface not
      linked to the primary site of infection. We found that bats responded to
      infection with a significant increase in lungs of transcripts for Cathelicidin
      (an anti-microbial peptide) as well as the immune modulators tumor necrosis
      factor alpha and interleukins 10 and 23. In conclusion, hibernating bats can
      respond to experimental P. destructans infection by activating expression of
      innate immune response genes. 

PMID- 25391019
TI  - Helicobacter pylori infection decreases metformin tolerance in patients with type
      2 diabetes mellitus.
AB  - AIM: This study assessed whether Helicobacter pylori infection could influence
      metformin tolerance in patients with type 2 diabetes mellitus. SUBJECTS AND
      METHODS: Demographic, anthropometric, ultrasound, and laboratory data were
      obtained from 415 metformin-naive patients with diabetes. H. pylori infection was
      assessed based on the (13)C-labeled urea breath test ((13)C-UBT). The study
      duration was 4 weeks, and all subjects started metformin from 500 mg/day to 1,500
      mg/day progressively. Gastrointestinal side effects were assessed each week, and
      the metformin doses were adjusted by the compliance. Gastrointestinal side
      effects were compared between H. pylori-positive and -negative groups. RESULTS:
      According to the (13)C-UBT results, 220 patients were categorized as H. pylori
      negative versus 195 as H. pylori positive. At baseline, the scoring of
      gastrointestinal symptoms showed no statistical difference between the two
      groups. After 4 weeks, for gastrointestinal symptoms such as abdominal pain,
      nausea, bloating, and anorexia, the respective percentages in H. pylori-positive
      and -negative subjects were 44.6% versus 21.8% (P < 0.01), 20.0% versus 9.6% (P <
      0.01), 47.7% versus 23.2% (P < 0.01), and 32.8% versus 12.3% (P < 0.01). The
      final metformin dose was 951.28 +/- 661.1 mg in H. pylori-positive subjects,
      significantly less than that in H. pylori-negative subjects (1,209.09 +/- 522.91
      mg) (P < 0.01). On multivariate analysis, female gender, H. pylori infection,
      body mass index, triglycerides, age, and low-density lipoprotein-cholesterol were
      the independent parameters associated with any gastrointestinal symptoms.
      CONCLUSIONS: Patients with diabetes having H. pylori infection demonstrated more
      gastrointestinal side effects than those without H. pylori infection after taking
      metformin. Furthermore, female gender, H. pylori infection, body mass index,
      triglycerides, age, and low-density lipoprotein-cholesterol are independent
      determinants of metformin's side effects.

PMID- 25391021
TI  - A continuous labour supply model in microsimulation: a life-cycle modelling
      approach with heterogeneity and uncertainty extension.
AB  - This paper advances a structural inter-temporal model of labour supply that is
      able to simulate the dynamics of labour supply in a continuous setting and
      addresses two main drawbacks of most existing models. The first limitation is the
      inability to incorporate individual heterogeneity as every agent is sharing the
      same parameters of the utility function. The second one is the strong assumption
      that individuals make decisions in a world of perfect certainty. Essentially,
      this paper offers an extension of marginal-utility-of-wealth-constant labour
      supply functions known as "Frisch functions" under certainty and uncertainty with
      homogenous and heterogeneous preferences. The lifetime models based on the fixed
      effect vector decomposition yield the most stable simulation results, under both
      certain and uncertain future wage assumptions. Due to its improved accuracy and
      stability, this lifetime labour supply model is particularly suitable for
      enhancing the performance of the life cycle simulation models, thus providing a
      better reference for policymaking. 

PMID- 25391020
TI  - The putative Leishmania telomerase RNA (LeishTER) undergoes trans-splicing and
      contains a conserved template sequence.
AB  - Telomerase RNAs (TERs) are highly divergent between species, varying in size and
      sequence composition. Here, we identify a candidate for the telomerase RNA
      component of Leishmania genus, which includes species that cause leishmaniasis, a
      neglected tropical disease. Merging a thorough computational screening combined
      with RNA-seq evidence, we mapped a non-coding RNA gene localized in a syntenic
      locus on chromosome 25 of five Leishmania species that shares partial synteny
      with both Trypanosoma brucei TER locus and a putative TER candidate-containing
      locus of Crithidia fasciculata. Using target-driven molecular biology approaches,
      we detected a ~2,100 nt transcript (LeishTER) that contains a 5' spliced leader
      (SL) cap, a putative 3' polyA tail and a predicted C/D box snoRNA domain.
      LeishTER is expressed at similar levels in the logarithmic and stationary growth
      phases of promastigote forms. A 5'SL capped LeishTER co-immunoprecipitated and co
      localized with the telomerase protein component (TERT) in a cell cycle-dependent
      manner. Prediction of its secondary structure strongly suggests the existence of
      a bona fide single-stranded template sequence and a conserved C[U/C]GUCA motif
      containing helix II, representing the template boundary element. This study paves
      the way for further investigations on the biogenesis of parasite TERT
      ribonucleoproteins (RNPs) and its role in parasite telomere biology. 

PMID- 25391022
TI  - Postponing sexual debut among university youth: how do men and women differ in
      their perceptions, values and non-penetrative sexual practices?
AB  - This study aimed to investigate gender differences in reasoning influencing the
      postponing of sexual debut among university youth in Lebanon. Findings aimed to
      develop understandings that might help inform future research on, and programme
      implementation of, young people's reproductive and sexual health. A cross
      sectional survey of sexuality and sexual practices, attitudes and perceptions was
      conducted among private university students in Lebanon using a secure online
      method. Of 1838 participating students, 48.7% indicated they had never engaged in
      oral, anal or vaginal sex (i.e., penetrative sexual activity) during their
      lifetime (n =  895). Common socio-cultural concerns regarding sexual initiation
      included: gaining a bad reputation (47%), social rejection (58%), religion (70%)
      and parental disapproval (61%). Women were four times more concerned than men
      regarding loss of reputation and self-respect, six times more so regarding
      parental disapproval and three times more likely to be concerned with societal
      disapproval. Intrapersonal concerns included fear of contradicting one's own
      beliefs (67%), feeling guilty afterwards (62%) and losing self-respect (55%).
      Women were four times more likely to feel loss of self-respect and six times more
      likely to think sex was disgusting. Underlying reasons for postponing sexual
      intercourse are linked to adopted fears and social pressures that are
      internalised, and reinforce existing gender inequalities and reaffirm
      discriminatory gender norms. 

PMID- 25391024
TI  - Torticollis: A Symptom in Severe Otitis Media.

PMID- 25391023
TI  - Traceable calibration, performance metrics, and uncertainty estimates of
      minirhizotron digital imagery for fine-root measurements.
AB  - Even though fine-root turnover is a highly studied topic, it is often poorly
      understood as a result of uncertainties inherent in its sampling, e.g.,
      quantifying spatial and temporal variability. While many methods exist to
      quantify fine-root turnover, use of minirhizotrons has increased over the last
      two decades, making sensor errors another source of uncertainty. Currently, no
      standardized methodology exists to test and compare minirhizotron camera
      capability, imagery, and performance. This paper presents a reproducible,
      laboratory-based method by which minirhizotron cameras can be tested and
      validated in a traceable manner. The performance of camera characteristics was
      identified and test criteria were developed: we quantified the precision of
      camera location for successive images, estimated the trueness and precision of
      each camera's ability to quantify root diameter and root color, and also assessed
      the influence of heat dissipation introduced by the minirhizotron cameras and
      electrical components. We report detailed and defensible metrology analyses that
      examine the performance of two commercially available minirhizotron cameras.
      These cameras performed differently with regard to the various test criteria and
      uncertainty analyses. We recommend a defensible metrology approach to quantify
      the performance of minirhizotron camera characteristics and determine sensor
      related measurement uncertainties prior to field use. This approach is also
      extensible to other digital imagery technologies. In turn, these approaches
      facilitate a greater understanding of measurement uncertainties (signal-to-noise
      ratio) inherent in the camera performance and allow such uncertainties to be
      quantified and mitigated so that estimates of fine-root turnover can be more
      confidently quantified. 

PMID- 25391025
TI  - Functional heterologous protein expression by genetically engineered probiotic
      yeast Saccharomyces boulardii.
AB  - Recent studies have suggested the potential of probiotic organisms to be adapted
      for the synthesis and delivery of oral therapeutics. The probiotic yeast
      Saccharomyces boulardii would be especially well suited for this purpose due to
      its ability, in contrast to probiotic prokaryotes, to perform eukaryotic post
      translational modifications. This probiotic yeast thus has the potential to
      express a broad array of therapeutic proteins. Currently, however, use of wild
      type (WT) S. boulardii relies on antibiotic resistance for the selection of
      transformed yeast. Here we report the creation of auxotrophic mutant strains of
      S. boulardii that can be selected without antibiotics and demonstrate that these
      yeast can express functional recombinant protein even when recovered from
      gastrointestinal immune tissues in mice. A UV mutagenesis approach was employed
      to generate three uracil auxotrophic S. boulardii mutants that show a low rate of
      reversion to wild type growth. These mutants can express recombinant protein and
      are resistant in vitro to low pH, bile acid salts, and anaerobic conditions.
      Critically, oral gavage experiments using C57BL/6 mice demonstrate that mutant S.
      boulardii survive and are taken up into gastrointestinal immune tissues on a
      similar level as WT S. boulardii. Mutant yeast recovered from gastrointestinal
      immune tissues furthermore retain expression of functional recombinant protein.
      These data show that auxotrophic mutant S. boulardii can safely express
      recombinant protein without antibiotic selection and can deliver recombinant
      protein to gastrointestinal immune tissues. These auxotrophic mutants of S.
      boulardii pave the way for future experiments to test the ability of S. boulardii
      to deliver therapeutics and mediate protection against gastrointestinal
      disorders. 

PMID- 25391027
TI  - Whole mitochondrial genome sequence and mutations of the hypertension model
      inbred rat strain (Muridae; Rattus).
AB  - We reported the complete mitochondrial genome sequencing of a important
      hypertension model inbred rat strain for the first time. The total length of the
      mitogenome was 16,310 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA
      genes, 22 transfer RNA genes and 1 non-coding control region. The mutation events
      contained in this strain were also reported. 

PMID- 25391026
TI  - A two-step strategy to enhance activity of low potency peptides.
AB  - Novel strategies are needed to expedite the generation and optimization of
      peptide probes targeting G protein-coupled receptors (GPCRs). We have previously
      shown that membrane tethered ligands (MTLs), recombinant proteins comprised of a
      membrane anchor, an extracellular linker, and a peptide ligand can be used to
      identify targeted receptor modulators. Although MTLs provide a useful tool to
      identify and/or modify functionally active peptides, a major limitation of this
      strategy is the reliance on recombinant protein expression. We now report the
      generation and pharmacological characterization of prototype peptide-linker-lipid
      conjugates, synthetic membrane anchored ligands (SMALs), which are designed as
      mimics of corresponding MTLs. In this study, we systematically compare the
      activity of selected peptides as MTLs versus SMALs. As prototypes, we focused on
      the precursor proteins of mature Substance P (SubP) and Cholecystokinin 4 (CCK4),
      specifically non-amidated SubP (SubP-COOH) and glycine extended CCK4 (CCK4-Gly
      COOH). As low affinity soluble peptides these ligands each presented a
      challenging test case for assessment of MTL/SMAL technology. For each ligand,
      MTLs and corresponding SMALs showed agonist activity and comparable subtype
      selectivity. In addition, our results illustrate that membrane anchoring
      increases ligand potency. Furthermore, both MTL and SMAL induced signaling can be
      blocked by specific non-peptide antagonists suggesting that the anchored
      constructs may be orthosteric agonists. In conclusion, MTLs offer a streamlined
      approach for identifying low activity peptides which can be readily converted to
      higher potency SMALs. The ability to recapitulate MTL activity with SMALs extends
      the utility of anchored peptides as probes of GPCR function. 

PMID- 25391028
TI  - Complete mitochondrial genome of Red-bellied Macaw (Orthopsittaca manilata): its
      comparison with mitogenome of Blue-throated Macaw (Ara glaucogularis).
AB  - The Red-bellied Macaw (Orthopsittaca manilata) is a species of the monotypic
      genus Orthopsittaca. The genus is one of the six genera, which form
      morphologically diverse group termed as Macaws. Individuals of Orthopsittaca
      manilata species are found in extremely large Amazonian area of South America. In
      this study, full mitochondrial genome of considered species was sequenced. It is
      16,985 bp long and contains 13 protein-coding genes, 2 rRNAs, 22 tRNAs and a
      control region. Its comparison with published Blue-throated Macaw (Ara
      glaucogularis) mitogenome revealed their high degree of identity. Presented
      Orthopsittaca manilata mitogenome is the first complete genomic sequence of this
      genus. It will enrich the resource of molecular markers for future examination of
      evolutionary diversification of Macaws. It will be also indispensable to refine
      the phylogenetic relationships within the tribe Arini.

PMID- 25391029
TI  - The complete mitochondrial genome sequence and mutations of the lung cancer model
      inbred rat strain (Muridae; Rattus).
AB  - We reported the complete mitochondrial genome sequencing of an important Lung
      cancer model inbred rat strain for the first time. The total length of the
      mitogenome was 16,312 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA
      genes, 22 transfer RNA genes and 1 non-coding control region. The mutation sites
      were analyzed by comparing with the reference BN strain. 

PMID- 25391030
TI  - Complete mitochondrial genome of Blue-headed Macaw (Primolius couloni): its
      comparison with mitogenome of Blue-throated Macaw (Ara glaucogularis).
AB  - Primolius is a genus of midsized Macaws comprising three species. Blue-headed
      Macaws (Primolius couloni) are native to eastern Peru, extreme western Brazil and
      north-western Bolivia. In this study, full mitochondrial genome of considered
      species was sequenced. It is 16,995 bp long and contains 13 protein-coding genes,
      2 rRNAs, 22 tRNAs and a control region. Its comparison with published Blue
      throated Macaw (Ara glaucogularis) mitogenome revealed their high degree of
      identity. Primolius couloni mitogenome is the first complete genomic sequence of
      this genus. It will be indispensable to refine the phylogenetic relationships
      within the tribe Arini and will enrich the resource of markers for systematic,
      phylogenetic and population genetic studies.

PMID- 25391031
TI  - Complete sequence and characterization of mitochondrial genome of Jianyang Daer
      goat (Capra hircus).
AB  - This study has presented the complete mitogenome of Jianyang Daer goat (Capra
      hircus), a crossbreed known for its high growth rate and good-meat quality in
      China. The mitogenome was 16,643 bp in length, including 33.54% A, 26.07% C,
      13.10% G and 27.29% T. It contained a non-coding control region, 2 ribosomal RNA
      genes, 13 protein-coding genes and 22 transfer RNA genes. Two kinds of
      inititiation codon and four types of termination codon were identified. Moreover,
      most of the genes were encoded on H-strand. These information will be useful for
      further investigation on the genetic divergence among Chinese domestic goats.

PMID- 25391032
TI  - Complete sequence of an ovarian cancer inbred Sprague-Dawley rat model
      mitochondrial genome.
AB  - The Sprague-Dawley rat strain is a commonly used model for ovarian cancer disease
      study. We sequenced this rat strain mitochondrial genome for the first time
      (GenBank Accession No. KM114604). Its mitogenome was 16,312 bp and coding 13
      protein-coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes. A total of
      96 SNPs were examined when compared to reference BN sequence. 

PMID- 25391033
TI  - The complete mitochondrial genome of Schizopygopsis chengi baoxingensis
      (Teleostei, Cyprinidae, Schizopygopsis).
AB  - Schizopygopsis chengi baoxingensis is endemic to the Baoxing River in China and
      may become an endangered species due to its very narrow habitat and the
      construction of hydropower dams. In this study, we successfully sequenced the
      first mitochondrial genome of S. c. baoxingensis. The mitogenome is 16,787 bp in
      length, containing 13 protein-coding genes, two rRNA genes, 22 tRNA genes and a
      control region (D-loop). The overall base composition of the H-strand is 28.5% A,
      26.2% T, 18.4% C, and 26.9% G, with a slight AT bias of 54.7%. The sequenced
      mtDNA genome of S. c. baoxingensis is similar in gene arrangement to that of
      other cyprinidaes except for a 191 bp non-coding region found between tRNA(Thr)
      and tRNA(Pro).

PMID- 25391034
TI  - Complete mitochondrial genome of Suzuki's Promolactis moth Promalactis suzukiella
      (Lepidoptera: Oecophoridae).
AB  - Suzuki's Promolactis moth, Promalactis suzukiella, is in the family Oecophoridae
      of lepidodpteran Gelechioidea. This species is native to Korea, Japan and Taiwan,
      but has been recently found in the eastern part of the United States. Sequence
      information on this genus including P. suzukiella is nearly absent due to its
      small size and difficulty with identification. Therefore, we sequenced the
      complete mitochondrial genome (mitogenome) of the species. The 15,507-bp long
      complete mitogenome consisted of a typical set of genes (13 protein-coding genes,
      two rRNA genes and 22 tRNA genes) with one major non-coding A + T-rich region,
      and the typical arrangement found in most Lepidoptera. The controversial start
      codon for cytochrome oxidase I gene was CGA without any alternatives. The 81 bp
      P. suzukiella tRNA(Lys) was longer than any other tRNAs (e.g. 60-71 bp) due to
      the presence of a duplicated TTCTAATG sequence located at the 3' end of
      tRNA(Lys).

PMID- 25391035
TI  - Description of the mitogenome of Gansu mole (Scapanulus oweni).
AB  - The Gansu mole Scapanulus oweni belongs to family Talpidae, and is distributed in
      the Central and Southwest China. In this study, the total mitochondrial genome of
      S. oweni was firstly determined. The genome is 16,826 bases in length and
      contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes
      and a displacement loop region, with a base composition of A 34.0%, G 13.5%, T
      28.7% and C 23.9%. All of the protein-coding genes initiate with the orthodox ATG
      start codon execpt for Nd2 and Nd3 begin with ATT, Nd4 and Nd5, start with GTG
      and ATA, respectively. Four types of stop codons are used by the coding genes,
      including TAA for Nd1, Cox1, Cox2, Atp8, Atp6, Nd4L, Nd5, Nd6, TAG for Nd2, AGA
      for Cytb, and an incomplete stop codon T for Cox3, Nd3 and Nd4. The mito-genomic
      data of Gansu mole, S. oweni will be useful in determining its taxonomic status
      within Talpidae.

PMID- 25391036
TI  - Complete mitochondrial DNA sequence of Lepus tolai (Leporidae: Lepus).
AB  - In the present study, we determined the complete nucleotide sequence of the
      mitochondrial (mt) genome of tolai hare, Lepus tolai (Leporidae: Lepus) by using
      polymerase chain reaction (PCR) technique. The entire mtDNA sequence is 17,472 bp
      long and contains 13 protein-coding genes, two ribosomal RNA, 22 transfer RNA
      gens and one long non-coding region known as the control region.

PMID- 25391037
TI  - On estimating the directionality distribution in pedicle trabecular bone from
      micro-CT images.
AB  - Our interest in the trabecular alignment within bone stems from the need to
      better understand the manner in which it can affect ultrasound propagation,
      particularly in pedicles. Within long bones it is well established that
      trabecular structures are aligned in an organized manner associated with the
      direction of load distribution; however, for smaller bones there are limited
      alignment studies. To investigate the directionality distribution in a
      quantitative manner we used a micro-CT to obtain three-dimensional (3D)
      structural data and developed analytical methods based on the special properties
      of Gabor filters. Implementation of these techniques has been developed and
      tested on a variety of simulated images as well as on 3D structures whose
      geometry is well-defined. To test the use of this technique we compared the
      results obtained on vertebral body trabecular bone with visual directionality and
      previous measurements by others. The method has been applied to six human pedicle
      samples in two orthogonal planes with results that provide reasonable proof-of
      principle evidence that the method is well suited for estimating the
      directionality distribution within pedicle bones. 

PMID- 25391038
TI  - The power of mobile health technologies and prescribing apps.

PMID- 25391040
TI  - Depression outcomes associated with an intervention implemented in employment
      training programs for low-income adolescents and young adults.
AB  - IMPORTANCE: Recent estimates indicate that 6.5 million adolescents and young
      adults in the United States are neither in school nor working. These youth have
      significant mental health concerns that require intervention. OBJECTIVE: To
      determine whether a mental health intervention, integrated into an employment
      training program that serves adolescents and young adults disconnected from
      school and work, can reduce depressive symptoms and improve engaged coping
      strategies. DESIGN, SETTING, AND PARTICIPANTS: A quasi-experimental study was
      conducted; 512 adolescents and young adults newly enrolling in one employment
      training program site were intervention participants, while 270 youth from a
      second program site were enrolled as controls. Participants were aged 16 to 23
      years and not in foster care. Study recruitment took place from September 1,
      2008, to May 31, 2011, with follow-up data collection occurring for 12 months
      after recruitment. Propensity score matching adjusted for observed baseline
      differences between the intervention and control groups. MAIN OUTCOMES AND
      MEASURES: Depressive symptoms measured on a Center for Epidemiologic Studies
      Depression Scale (CES-D) and engaged coping strategies. RESULTS: The mean age of
      participants was 19 years, 93.7% were African American, and 49.4% were male. Six-
      and 12-month follow-up rates were 61.0% (n = 477) and 56.8% (n = 444),
      respectively. Males in the intervention group with high baseline depressive
      symptoms exhibited a statistically significant decrease in depressive symptoms at
      12 months (5.64-point reduction in CES-D score; 95% CI, -10.30 to -0.96; P = .02)
      compared with similar males in the control group. A dosage effect was observed at
      12 months after the intervention, whereby males with greater intervention
      exposure showed greater improvement in depressive symptoms compared with similar
      males with lower intervention doses (effect on mean change in CES-D score, -3.37;
      95% CI, -6.72 to -0.09; P = .049). Males and females in the intervention group
      were more likely than participants in the control group to increase their engaged
      coping skills, with statistically significant differences found for males (effect
      on mean change in CES-D score, 0.32; 95% CI, 0.14-0.50; P = .001) and females
      (effect on mean change in CES-D score, 0.19; 95% CI, 0.01-0.37; P = .047) at 12
      months. CONCLUSIONS AND RELEVANCE: Given the growing number of adolescents and
      young adults using employment training programs and the mental health needs of
      this population, increased efforts should be made to deliver mental health
      interventions in these settings that usually focus primarily on academic and job
      skills. Ways to extend the effect of intervention for females and those with
      lower levels of depressive symptoms should be explored.

PMID- 25391041
TI  - Intracellular signaling transduction pathways triggered by a well-known anti-GHR
      monoclonal antibody, Mab263, in vitro and in vivo.
AB  - A series of studies have reported that monoclonal antibody 263 (Mab263), a
      monoclonal antibody against the growth hormone receptor (GHR), acts as an agonist
      in vitro and in vivo. However, the intracellular signaling pathways triggered by
      Mab263 have not yet been delineated. Therefore, we examined the intracellular
      signaling pathways induced by Mab263 in vivo and in vitro in the present study.
      The results show that this antibody activated janus kinase 2 (JAK2), signal
      transducer and activator of transcription 3 (STAT3), STAT1 and extracellular
      signal-regulated kinase 1/2 (ERK1/2), but not STAT5. The phosphorylation kinetics
      of JAK2, STAT3/1 and ERK1/2 induced by Mab263 were subsequently analyzed in dose
      response and time course experiments. Our observations indicate that Mab263
      induced different intracellular signaling pathways than GH, which indicates that
      Mab263 is a signal-specific molecule and that Mab263 may be a valuable biological
      reagent to study the mechanism(s) of GHR-mediated intracellular signaling
      pathways. 

PMID- 25391042
TI  - Depletion of C3orf1/TIMMDC1 inhibits migration and proliferation in 95D lung
      carcinoma cells.
AB  - In our previous study, we identified an association of high expression of c3orf1,
      also known as TIMMDC1 (translocase of inner mitochondrial membrane domain
      containing protein 1), with metastatic characteristics in lung carcinoma cells.
      To investigate the preliminary function and mechanism of this mitochondrial
      protein, we depleted C3orf1 expression by introducing siRNA into 95D lung
      carcinoma cells. We demonstrated that C3orf1 depletion significantly suppressed
      95D cell growth and migration. We confirmed C3orf1 localization in the inner
      mitochondrial membrane and showed that mitochondrial viability, membrane
      potential, and ATPase activity were remarkably reduced upon depletion of C3orf1.
      Microarray data indicated that genes involved in regulation of cell death,
      migration, and cell-cycle arrest were significantly altered after C3orf1
      depletion for 48 h. The expression of genes involved in focal adhesion, ECM
      receptor interaction, and p53-signaling pathways were notably altered.
      Furthermore, cell-cycle arrest genes such as CCNG2 and PTEN as well as genes
      involved in cell migration inhibition, such as TIMP3 and COL3A1, were upregulated
      after C3orf1 depletion in 95D cells. Concurrently, expression of the migration
      promoting gene NUPR1 was markedly reduced, as confirmed by real-time PCR. We
      conclude that C3orf1 is critical for mitochondrial function, migration, and
      proliferation in 95D lung carcinoma cells. Depletion of C3orf1 inhibited cell
      migration and cell proliferation in association with upregulation of genes
      involved in cell-cycle arrest and cell migration inhibition. These results
      suggest that C3orf1 (TIMMDC1) may be a viable treatment target for lung
      carcinoma, and that further study of the role of this protein in lung carcinoma
      pathogenesis is justified. 

PMID- 25391043
TI  - A functional monomer is not enough: principal component analysis of the influence
      of template complexation in pre-polymerization mixtures on imprinted polymer
      recognition and morphology.
AB  - In this report, principal component analysis (PCA) has been used to explore the
      influence of template complexation in the pre-polymerization phase on template
      molecularly imprinted polymer (MIP) recognition and polymer morphology. A series
      of 16 bupivacaine MIPs were studied. The ethylene glycol dimethacrylate (EGDMA)
      crosslinked polymers had either methacrylic acid (MAA) or methyl methacrylate
      (MMA) as the functional monomer, and the stoichiometry between template,
      functional monomer and crosslinker was varied. The polymers were characterized
      using radioligand equilibrium binding experiments, gas sorption measurements,
      swelling studies and data extracted from molecular dynamics (MD) simulations of
      all-component pre-polymerization mixtures. The molar fraction of the functional
      monomer in the MAA-polymers contributed to describing both the binding, surface
      area and pore volume. Interestingly, weak positive correlations between the
      swelling behavior and the rebinding characteristics of the MAA-MIPs were exposed.
      Polymers prepared with MMA as a functional monomer and a polymer prepared with
      only EGDMA were found to share the same characteristics, such as poor rebinding
      capacities, as well as similar surface area and pore volume, independent of the
      molar fraction MMA used in synthesis. The use of PCA for interpreting
      relationships between MD-derived descriptions of events in the pre-polymerization
      mixture, recognition properties and morphologies of the corresponding polymers
      illustrates the potential of PCA as a tool for better understanding these complex
      materials and for their rational design. 

PMID- 25391044
TI  - Rosmarinus officinalis leaves as a natural source of bioactive compounds.
AB  - In an extensive search for bioactive compounds from plant sources, the
      composition of different extracts of rosemary leaves collected from different
      geographical zones of Serbia was studied. The qualitative and quantitative
      characterization of 20 rosemary (Rosmarinus officinalis) samples, obtained by
      microwave-assisted extraction (MAE), was determined by high performance liquid
      chromatography coupled to electrospray quadrupole-time of flight mass
      spectrometry (HPLC-ESI-QTOF-MS). The high mass accuracy and true isotopic pattern
      in both MS and MS/MS spectra provided by the QTOF-MS analyzer enabled the
      characterization of a wide range of phenolic compounds in the extracts, including
      flavonoids, phenolic diterpenes and abietan-type triterpenoids, among others.
      According to the data compiled, rosemary samples from Sokobanja presented the
      highest levels in flavonoids and other compounds such as carnosol,
      rosmaridiphenol, rosmadial, rosmarinic acid, and carnosic acid. On the other
      hand, higher contents in triterpenes were found in the extracts of rosemary from
      Glozan (Vojvodina). 

PMID- 25391047
TI  - Surgeon's 30-day outcomes supporting the carotid revascularization endarterectomy
      versus stenting trial.
AB  - IMPORTANCE: While the Carotid Revascularization Endarterectomy Versus Stenting
      Trial (CREST) has been widely accepted as a landmark trial establishing an
      equivalent risk of major adverse events following carotid endarterectomy (CEA) or
      carotid artery stenting (CAS), the applicability of these findings to single
      centers has been questioned owing to the rigid selection criteria for
      investigators in the study. Although refuted by the findings of a subsequent
      study, a substudy of CREST established a higher periprocedural stroke rate for
      CAS when the surgeon was a vascular surgeon. OBJECTIVE: To present our 30-day
      results of stroke, death, myocardial infarction, and composite major adverse
      events to determine if a single vascular surgeon's outcomes at our hospital are
      consistent with the results of CREST. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective analysis of patients with high-grade carotid artery stenosis
      treated with CEA or CAS by a vascular surgeon at our institution from September
      9, 2005, through December 17, 2012, was performed. A chi2 analysis was used to
      compare the incidence of specific high-risk patient characteristics in each
      group. The Fisher exact test was used to compare the risks of stroke, death,
      myocardial infarction, and composite major adverse events between CEA and CAS.
      These results were then compared with those reported in CREST. RESULTS: A total
      of 182 cases (94 CAS and 88 CEA) performed by a single vascular surgeon were
      included for analysis. While in CREST the periprocedural risk of stroke was
      higher following CAS (4.1% vs 2.3%, P = .01) and the risk of myocardial
      infarction was higher following CEA (2.3% vs 1.1%, P = .03), there was no
      significant difference in the incidence of these outcomes between the 2 treatment
      modalities in our study. When compared with CREST, our rates of myocardial
      infarction, stroke, death, and composite adverse events (CEA, 4.5% vs 3.4%; P =
      .79; CAS, 5.2% vs 4.3%; P >.99) were no different. CONCLUSIONS AND RELEVANCE:
      Similar to CREST, the 30-day risk of composite major adverse events was
      equivalent for the 2 treatment modalities. We attribute our comparable incidence
      of perioperative stroke with CAS and CEA to improved patient selection. We
      excluded most patients older than 80 years and those with complex anatomy from
      consideration for CAS. Our results confirm those of CREST and demonstrate that
      both CEA and CAS can be performed safely by a vascular surgeon in properly
      selected patients.

PMID- 25391046
TI  - Analysis of human TAAR8 and murine Taar8b mediated signaling pathways and
      expression profile.
AB  - The thyroid hormone derivative 3-iodothyronamine (3-T1AM) exerts metabolic
      effects in vivo that contradict known effects of thyroid hormones. 3-T1AM acts as
      a trace amine-associated receptor 1 (TAAR1) agonist and activates G(s) signaling
      in vitro. Interestingly, 3-T1AM-meditated in vivo effects persist in Taar1
      knockout-mice indicating that further targets of 3-T1AM might exist. Here, we
      investigated another member of the TAAR family, the only scarcely studied mouse
      and human trace-amine-associated receptor 8 (Taar8b, TAAR8). By RT-qPCR and
      locked-nucleic-acid (LNA) in situ hybridization, Taar8b expression in different
      mouse tissues was analyzed. Functionally, we characterized TAAR8 and Taar8b with
      regard to cell surface expression and signaling via different G-protein-mediated
      pathways. Cell surface expression was verified by ELISA, and cAMP accumulation
      was quantified by AlphaScreen for detection of G(s) and/or G(i/o) signaling.
      Activation of G-proteins G(q/11) and G(12/13) was analyzed by reporter gene
      assays. Expression analyses revealed at most marginal Taar8b expression and no
      gender differences for almost all analyzed tissues. In heart, LNA-in situ
      hybridization demonstrated the absence of Taar8b expression. We could not
      identify 3-T1AM as a ligand for TAAR8 and Taar8b, but both receptors were
      characterized by a basal G(i/o) signaling activity, a so far unknown signaling
      pathway for TAARs.

PMID- 25391048
TI  - Spectral-domain optical coherence tomography findings after indocyanine green
      assisted vitrectomy for idiopathic macular hole.
AB  - PURPOSE: To report the intraretinal changes seen on the spectral-domain optical
      coherence tomography after indocyanine green (ICG) assisted internal limiting
      membrane peeling for macular hole. METHODS: A 76-year-old woman with closed
      macular hole after ICG-assisted internal limiting membrane peeling presented poor
      visual acuity. Infrared-red, fundus autofluorescence, ICG fluorescence, time
      domain OCT and spectral-domain optical coherence tomography images were obtained.
      RESULTS: Spectral-domain optical coherence tomography showed the irregular bumps
      of the retinal pigment epithelium, thinning of the overlying photoreceptor inner
      and outer segment layer, and enhanced reflectivity of external limiting membrane
      layer that corresponded to residual ICG fluorescence dots. The area of retinal
      pigment epithelium changes and inner and outer segment layer disruption seemed to
      correspond to residual ICG fluorescence in the previous macular hole bed.
      CONCLUSION: The intraretinal changes were observed in areas of retained ICG after
      ICG-assisted internal limiting membrane peeling. Spectral-domain optical
      coherence tomography detected these changes clearly.

PMID- 25391049
TI  - Scotoma formation after exposure of retinal pigmented epithelium to indocyanine
      green.
AB  - PURPOSE: To describe objective, clinical evidence of retinal pigmented epithelial
      (RPE) cell toxicity after exposure to indocyanine green (ICG) in two patients.
      METHODS: Using color photos, we show the physical changes in the retina after RPE
      exposure to ICG. In addition, we present Humphrey visual field examination
      results, which correlate precisely with sites of ICG contact with the RPE layer.
      PATIENTS: A case series of two patients who underwent vitrectomy and membrane
      stripping with ICG use by a single surgeon. RESULTS: Visual examination, color
      photos, and Humphrey visual field examination results postoperatively reveal
      scotoma formation corresponding precisely to the size and location of ICG contact
      with the RPE layer. CONCLUSION: Our two case reports support the theory of ICG
      solution toxicity to RPE cells, while emphasizing that exposure of RPE to ICG
      should be avoided in retinal surgery.

PMID- 25391045
TI  - Molecular mechanisms underlying the effects of statins in the central nervous
      system.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to
      as statins, are widely used in the treatment of dyslipidaemia, in addition to
      providing primary and secondary prevention against cardiovascular disease and
      stroke. Statins' effects on the central nervous system (CNS), particularly on
      cognition and neurological disorders such as stroke and multiple sclerosis, have
      received increasing attention in recent years, both within the scientific
      community and in the media. Current understanding of statins' effects is limited
      by a lack of mechanism-based studies, as well as the assumption that all statins
      have the same pharmacological effect in the central nervous system. This review
      aims to provide an updated discussion on the molecular mechanisms contributing to
      statins' possible effects on cognitive function, neurodegenerative disease, and
      various neurological disorders such as stroke, epilepsy, depression and CNS
      cancers. Additionally, the pharmacokinetic differences between statins and how
      these may result in statin-specific neurological effects are also discussed. 

PMID- 25391050
TI  - Indocyanine green toxicity of the retina after cataract surgery: a case report.
AB  - PURPOSE: To report a single case of indocyanine green (ICG) toxicity of the
      retina after cataract surgery. METHODS: A patient from an academic clinical
      practice was observed with visual field testing, fundus photography, optical
      coherence tomography, and electroretinography (ERG) following the occurrence of
      ICG toxicity of the retina after cataract surgery. The main outcomes were final
      visual acuity, visual fields, and ERG result. RESULTS: ERG revealed initial
      subnormal dark-adapted response with normalization 6 months after surgery. The
      pericentral scotoma found by visual field testing disappeared. Fundus photography
      of the affected eye showed clearing of ICG stains. CONCLUSIONS: The patient had
      substantial improvement of ICG-mediated retinal toxicity.

PMID- 25391051
TI  - Long-term follow-up in enhanced s-cone syndrome.
AB  - PURPOSE: To report the long-term follow-up of a case of enhanced S-cone syndrome
      (ESCS). METHODS: Retrospective chart review. RESULTS: The patient was
      misdiagnosed with atypical retinitis pigmentosa at 17 years of age. Twenty-seven
      years of follow-up showed slow deterioration but relative preservation of vision.
      The most striking clinical feature was the formation of a ring of heavy round
      pigment clumping around the vascular arcades. Electroretinogram was reported as
      extinguished in advanced stages of the condition. Genetic testing revealed the
      most common mutation of the NR2E3 gene reported in the Goldmann-Favre
      syndrome/ESCS entity. CONCLUSION: Visual acuity can be relatively preserved over
      the course of ESCS. In advanced stages, genetic testing can be a valuable
      diagnostic tool.

PMID- 25391052
TI  - Dorzolamide use in the management of macular cysts in a patient with enhanced s
      cone syndrome.
AB  - PURPOSE: To determine the efficacy of dorzolamide ophthalmic solution, a carbonic
      anhydrase inhibitor, for treating macular schisis in enhanced S-cone syndrome.
      METHODS: A 12-year-old white boy was diagnosed with enhanced S-cone syndrome
      based on the patient's history of night blindness, fundus examination, and
      electroretinogram testing that showed nondetectible rod function and atypical
      cone function consistent with an overabundance of blue cones. Time domain optical
      coherence tomography (OCT) baseline scans confirmed the presence of macular
      cysts, and the patient was started on dorzolamide ophthalmic drops twice a day. A
      Fourier domain-OCT unit was used to monitor any changes in the macular cysts.
      RESULTS: After 8 weeks of starting the eye drops, the Fourier domain OCT showed
      an improvement in the macular cysts of the right eye with notable but more
      moderate changes in the left. Visual acuity improved one line in the right eye
      compared with baseline. Ten weeks later, the patient showed a further improvement
      in macular cysts by OCT testing in both eyes, with visual acuity improvement of
      one line in the left eye, and sustained one line improvement in the right.
      CONCLUSION: The treatment of macular cysts using a topical carbonic anhydrase
      inhibitor twice a day can potentially reduce foveal cystic changes and possibly
      improve visual acuity in at least some patients with enhanced S-cone syndrome.

PMID- 25391053
TI  - Intravitreal bevacizumab in the treatment of choroidal neovascularization from a
      traumatic choroidal rupture in a 9-year-old child.
AB  - PURPOSE: To describe a case in which a 9-year-old boy who sustained a traumatic
      choroidal rupture, and later developed choroidal neovascularization (CNV), was
      successfully treated with intravitreal bevacizumab. METHODS: Comprehensive
      ophthalmic evaluation, including fundus photography, fluorescein angiography,
      optical coherence tomography, and B-scan ultrasonography, was done to follow the
      patient's course and response to treatment over a 2-month period. RESULTS:
      Preinjection visual acuity was 20/200. Fluorescein angiography showed significant
      leakage, and optical coherence tomography revealed macular edema. One month after
      injection, visual acuity was 20/20, with resolution of leakage and edema by
      fluorescein angiography and optical coherence tomography, respectively.
      CONCLUSION: There was dramatic improvement in visual acuity from a single
      intravitreal injection of bevacizumab. This case shows promise for future
      applications of bevacizumab as treatment of CNV arising from a traumatic
      choroidal rupture.

PMID- 25391054
TI  - Spontaneous relief of vitreomacular traction and regression of neovascularization
      in eales disease after intravitreal injection of bevacizumab.
AB  - PURPOSE: To report the use and sequelae of intravitreal injection of bevacizumab
      (Avastin; Roche) in Eales disease with persistent active neovascularization and
      vitreomacular traction. METHODS: Intravitreal injection of bevacizumab was used
      to treat Eales disease with a persistent large neovascular frond, vitreous
      hemorrhage, and vitreomacular traction. RESULTS: After the injection, there was
      spontaneous relief of the vitreomacular traction and improvement in visual
      acuity. Rapid regression of the neovascular frond resulted in a traction retinal
      break, which was successfully managed with barrage laser photocoagulation.
      CONCLUSION: Intravitreal injection of bevacizumab seems to be a good option in
      managing persistent neovascularization in Eales disease. These patients need
      regular follow-up to recognize the complications that may arise due to the rapid
      regression of neovascularization.

PMID- 25391055
TI  - Resolution of a giant pigment epithelial detachment after treatment with
      intravitreal bevacizumab.
AB  - PURPOSE: To describe a patient with a giant pigment epithelial detachment (PED)
      successfully treated with intravitreal bevacizumab. DESIGN: Retrospective,
      observational case report. METHODS: The patient's records were reviewed. RESULTS:
      An 81-year-old man with history of age-related macular degeneration was seen on
      routine follow-up examination with an asymptomatic PED temporal to the macula in
      the right eye and visual acuity of 20/40. The patient was observed. Ten months
      later, the patient was found to have decreased vision to 20/80 and massive
      enlargement of the PED, with extension from the temporal equator into the macula.
      Optical coherence tomography of the macula showed a PED with overlying
      intraretinal cysts. The patient was given injections of intravitreal bevacizumab
      for every 4 months (1.25 mg) with complete resolution of the PED and return to
      baseline visual acuity of 20/40. CONCLUSION: Giant PED secondary to exudative age
      related macular degeneration can be successfully treated with intravitreal
      bevacizumab.

PMID- 25391056
TI  - Fundus autofluorescence in acute idiopathic maculopathy.
AB  - PURPOSE: To characterize changes in fluorophore metabolism during acute
      idiopathic maculopathy (AIM) using autofluorescence (AF) imaging. METHODS: AF
      imaging was performed during the clinical course of a 38-year-old man with AIM.
      RESULTS: AF imaging initially revealed distinct hypofluorescence corresponding to
      a clinical pattern of retinal pigment epithelium (RPE) hypopigmentation and a
      window defect seen on fluorescein angiography. This hypofluorescence essentially
      resolved within 1 week, but adjacent hyperfluorescent features persisted over the
      course of resolution of the macular detachment. Six weeks later, the patient
      reported complete resolution of the central scotoma, and fundus examination and
      optical coherence tomography revealed resolution of the detachment. AF revealed
      mild persistent nasal hyperfluorescence, but the overall reflectance was closer
      in quality to that of the noninvolved retina. CONCLUSION: AF features in AIM
      reveal an acute disruption of fluorophore metabolism that resolves fairly
      rapidly, consistent with the concept of AIM as a self-limited inflammatory
      process of the RPE.

PMID- 25391057
TI  - Bilateral central retina vein occlusion associated with obesity-hypoventilation
      syndrome (pickwickian syndrome).
AB  - PURPOSE: To describe bilateral central retinal vein occlusion (CRVO) as a
      clinical manifestation of obesity-hypoventilation syndrome (pickwickian
      syndrome). METHOD: Case report. PATIENT: A 37-year-old Hispanic man with morbid
      obesity and obstructive sleep apnea who suddenly developed bilateral loss of
      vision. RESULTS: Laboratory studies disclosed the following: hematocrit, 81%;
      body mass index, 55 kg/m; PaCO2, 52 mmHg; and blood oxygen saturation (SaO2),
      54%. Polysomnography demonstrated 45 obstructive apneas and 133 obstructive
      hypopneas, with abnormal movements of the inferior limbs during sleep.
      DISCUSSION: Hypoxia and hypercapnia produce severe erythrocytosis that causes a
      change in blood viscosity. This may facilitate thrombus formation at the lamina
      cribrosa of both eyes manifested as bilateral CRVO.

PMID- 25391058
TI  - Periocular corticosteroid in malignant hypertensive and preeclampsic
      choroidopathy.
AB  - INTRODUCTION: Disk edema and serous macular detachment in either malignant
      hypertension or preeclampsia require several weeks to resolve, leaving these
      young active affected subjects with unilateral or bilateral visual handicap.
      METHODS: The authors treated two patients with visual loss by sub-Tenon
      corticosteroid. RESULTS: Visual improvement occurred within 1 week of the
      periocular corticosteroid from finger counting at 6 m to 20/70 in a woman with
      preeclampsia and from bilateral 20/50 to 20/25 in the right eye and 20/20 in the
      left eye in a man with malignant hypertension. CONCLUSION: In addition to blood
      pressure control, periocular corticosteroid can fasten visual recovery in serous
      macular detachment and disk edema from preeclampsia or malignant hypertension.

PMID- 25391059
TI  - Large turbid retinal pigment epithelial detachment camouflaging an underlying
      choroidal nevus.
AB  - PURPOSE: To report an unusual large turbid detachment of the retinal pigment
      epithelium (RPE) overlying a hidden choroidal nevus. METHODS: Case report.
      RESULTS: A 51-year-old woman was referred with an asymptomatic yellow subretinal
      mass in the left eye presumed to represent a choroidal metastasis or melanoma.
      Visual acuity was 20/20 in both eyes. Ophthalmoscopy of the left eye revealed a
      well defined, abruptly elevated, dome-shaped amelanotic lesion temporal to the
      macular area measuring 4 mm in basal dimension and 2.2 mm in thickness. There was
      no evidence of drusen, inflammation, or hemorrhage. Fluorescein angiography and
      optical coherence tomography suggested RPE detachment from unknown cause. After 6
      years follow-up, the RPE detachment resolved, exposing an underlying chronic
      choroidal nevus as the etiology. CONCLUSIONS: Choroidal nevus can produce an
      overlying RPE detachment that completely obscures the underlying lesion.

PMID- 25391060
TI  - Metastatic cutaneous melanoma to the ciliary body in familial atypical mole
      melanoma (fam-m) syndrome.
AB  - PURPOSE: To report a case of metastatic melanoma to the ciliary body in familial
      atypical mole-melanoma syndrome. METHODS: Retrospective case report. PATIENTS: A
      46-year-old woman presented with a ciliary body melanoma and tumor seeding of the
      anterior chamber structures. RESULTS: Biopsy and systemic workup suggested
      metastatic origin. CONCLUSIONS: Correlation is noted between the noncohesive
      epithelioid cell type and seeding of the anterior chamber.

PMID- 25391061
TI  - Choroidal melanoma masquerading as panuveitis in a patient with multiple myeloma.
AB  - BACKGROUND: Choroidal melanoma can sometimes present with associated anterior
      uveitis or panuveitis that can mask the underlying intraocular neoplasm and
      confound the diagnosis. METHODS: Retrospective chart review. RESULTS: A 58-year
      old woman presented with recurrent episodes of hypopyon, severe panuveitis, and a
      choroidal mass lesion in the right eye. Extensive systemic workup led to a
      diagnosis of multiple myeloma. Despite successful treatment of myeloma, the
      choroidal mass persisted and increased in size. Transscleral biopsy of the mass
      lesion revealed primary malignant choroidal melanoma. CONCLUSION: This case
      demonstrates that choroidal melanoma can present as masquerade syndrome with
      significant intraocular inflammation. Such cases pose a significant diagnostic
      dilemma to the clinician. Transscleral choroidal biopsy can provide critical
      information that is essential to establishing a definitive diagnosis and
      treatment plan.

PMID- 25391062
TI  - Malignant optic glioma presenting as an acute anterior optic neuropathy.
AB  - PURPOSE: To describe an uncommon case of malignant optic glioma and the
      challenges in its diagnosis. METHODS: Case report with funduscopic, magnetic
      resonance imaging (MRI), and automated field test correlations. PATIENT: A 60
      year-old man presented with a 1-week history of left optic disk swelling and
      optic neuropathy that was initially diagnosed as nonarteritic anterior ischemic
      optic neuropathy (NA-AION). RESULTS: His clinical course deteriorated with
      progressive vision loss, acute orbital inflammation, and central retinal vein and
      artery occlusion, despite an improvement with a short course of steroids. MRI
      revealed enhancement of the left optic nerve, chiasm, and left optic tract.
      Initial optic nerve biopsy was negative and biopsy of optic tract confirmed a
      diagnosis of glioblastoma multiforme grade 4. The patient died 4 months after
      biopsy despite chemotherapy and radiotherapy. CONCLUSION: The diagnoses of
      malignant optic glioma, anterior ischemic optic neuropathy, and optic neuritis
      have significant overlap of signs and symptoms. The authors report a case that
      demonstrates the difficulties in diagnosis, and propose additional presenting
      features of malignant optic glioma.

PMID- 25391063
TI  - Macular ischemia associated with imatinib mesylate therapy for chronic myeloid
      leukemia.
AB  - PURPOSE: Imatinib mesylate (Gleevec, East Hanover, NJ) is a drug approved for the
      treatment of patients with Philadelphia chromosome-positive chronic myeloid
      leukemia (CML) or Kit-positive gastrointestinal stromal tumors. A case of
      ischemic maculopathy associated with imatinib mesylate therapy is reported.
      METHODS: A 62-year-old woman with a 16-year history of CML was treated with
      imatinib mesylate, initially at a daily dose of 400 mg that was decreased to 300
      mg due to systemic side effects. Several weeks after beginning imatinib mesylate
      therapy, she developed blurred vision (greater in the left eye than in the right
      eye). RESULTS: Fundus examination of both eyes revealed retinal telangiectasia
      with intraretinal hemorrhages and perifoveal retinal telangiectasia. Fluorescein
      angiography showed macular ischemia (greater in the left eye than in the right
      eye). Late perifoveal leakage was present surrounding the macular ischemic zone.
      Visual acuity was reduced to 20/30 in the right eye and 20/100 in the left eye,
      which did not improve over 10 months of follow-up. CONCLUSION: Imatinib mesylate
      may be associated with ischemic maculopathy that can severely compromise vision.
      It may be necessary for patients receiving this therapy to be monitored for
      associated visual symptoms and funduscopic abnormalities.

PMID- 25391064
TI  - Acute glaucoma secondary to angle obstruction by triamcinolone crystals.
AB  - PURPOSE: To present a case of acute glaucoma secondary to massive transit of
      triamcinolone acetonide into the anterior chamber in a pseudophakic,
      vitrectomized eye following intravitreal injection for treatment of cystoid
      macular edema. SETTING: Manchester Royal Eye Hospital. METHOD: Case study.
      CONCLUSION: In vitrectomized eyes with open posterior capsule receiving high dose
      intravitreal triamcinolone, it is prudent to perform pressure check within a week
      of injection.

PMID- 25391065
TI  - Intravitreal injection of triamcinolone acetonide to treat cystoid foveal edema
      associated with coats' disease.
AB  - PURPOSE: To investigate the efficacy of intravitreal injection of triamcinolone
      acetonide (TA) for treatment of cystoid foveal edema (CFE) associated with Coats'
      disease. METHODS AND PATIENT: A 32-year-old man with a 28-month history of Coats'
      disease received an intravitreal TA injection (4 mg) in the right eye. RESULTS:
      Visual acuity improved from 20/200 to 20/50, and foveal thickness decreased from
      701 MUm to 216 MUm 45 days after treatment. CONCLUSION: Intravitreal TA injection
      might temporarily improve visual acuity in eyes with CFE associated with Coats'
      disease.

PMID- 25391066
TI  - Massive coats disease-like tumor after retinal detachment.
AB  - PURPOSE: To describe two patients with peripheral Coats disease-like tumor
      reaction years after surgical repair for rhegmatogenous retinal detachment.
      METHODS: Retrospective review of two clinical cases. RESULTS: Patient 1 presented
      with visual deterioration caused by a retinal angiomatous tumor and lipid
      exudates originating from telangiectatic vessels on the scleral buckle 8 years
      after vitrectomy and encircling band surgery for a giant retinal tear. In Patient
      2, a vascularized retinal mass was detected during vitrectomy for a vitreous
      hemorrhage 24 years after scleral buckling procedures. Both patients were highly
      myopic and had no history of scleral perforation or angiomatous proliferation
      before surgery. They underwent vitrectomy and removal of the vascularized tumor.
      Histologic examination revealed wide lacunae filled with erythrocytes, connective
      tissue strands with inflammatory cells, and capillaries that showed thickened
      multilamellar basement membranes. CONCLUSION: Secondary Coats disease-like tumor
      reaction may occur as a late complication years after successful retinal
      detachment surgery and may be caused by a chronic ischemic and inflammatory
      stimulus induced by prominent buckling elements in highly myopic eyes.

PMID- 25391067
TI  - Takayasu disease revealed by bilateral loss of vision.
AB  - PURPOSE: Takayasu arteritis is a nonspecific granulomatous inflammatory
      arteriopathy of unknown cause, most frequently diagnosed in young Asian women.
      The authors present an atypical initial presentation of Takayasu disease with
      bilateral loss of vision in a young Haitian man. METHODS: Case report. RESULTS:
      The presenting feature was bilateral loss of vision, a result of malignant
      hypertensive retinopathy and choroidopathy. Systemic evaluation disclosed
      inflammatory signs and renal artery obstruction which caused the malignant
      hypertension. CONCLUSION: This case, involving an unusual presentation of
      Takayasu disease, illustrates how a malignant hypertensive retinopathy and
      choroidopathy led to the ultimate diagnosis of Takayasu disease.

PMID- 25391068
TI  - Delayed, spontaneous conversion of type 2 closure to type 1 closure following
      surgery for traumatic and idiopathic macular holes.
AB  - PURPOSE: To report delayed improvement in macular hole closure configuration from
      Type 2 to Type 1 occurring months after internal limiting membrane peeling in two
      patients with macular hole. METHODS: Case 1 underwent surgery for a post
      traumatic macular hole. Case 2 underwent surgery for an idiopathic macular hole.
      RESULTS: Six weeks after surgery, Type 2 macular hole closure was documented by
      optical coherence tomography in both cases. Months later, spontaneous conversion
      of closure to Type 1 associated with visual gain was observed. CONCLUSION:
      Delayed, spontaneous conversion of Type 2 closure to Type 1 closure can occur
      several months after surgery for traumatic and idiopathic macular holes. This may
      be associated with improved visual outcomes.

PMID- 25391069
TI  - Optical coherence tomography features of x-linked choroideremia.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) features of X-linked
      choroideremia (CHM). DESIGN: Prospective, observational case series. PATIENTS AND
      METHODS: Color fundus photography, fluorescein angiography, indocyanine green
      angiography, and OCT were performed for four patients (eight eyes) with CHM.
      RESULTS: In areas of angiographic choriocapillaris loss, OCT revealed retinal
      thinning (mean, 124 MUm [range, 97-150 MUm) and increased reflectivity of the
      choroid. On the contrary, in areas of preserved choriocapillaris, retinal
      thickness was within normal limits (mean, 256 MUm [range, 238-284 MUm]; P <
      0.001). CONCLUSION: OCT revealed a correlation between retinal thickness and
      choriocapillaris preservation in CHM.

PMID- 25391070
TI  - Progressive optical coherence tomography deterioration in chloroquine
      maculopathy.
AB  - PURPOSE: To report optical coherence tomography (OCT) progressive changes in
      chloroquine maculopathy. DESIGN: Observational case report. METHODS: Both eyes of
      a patient with chloroquine maculopathy were examined serially with OCT. RESULTS:
      OCT demonstrated diffuse retinal thinning involving the fovea and perifoveal area
      in each eye, particularly involving the outer retina, with loss of the
      photoreceptor outer hyperreflective lamina proximal to the lamina corresponding
      to the retinal pigment epithelium (RPE). The temporal nerve fiber layer was
      mildly thinned. Repeat OCT showed progressive macular thinning. CONCLUSIONS: OCT
      findings are consistent with histopathologic studies that advanced chloroquine
      toxicity affects the nerve fiber layer and the outer retinal layers, and confirm
      reports that severe maculopathy may progress despite cessation of therapy. The
      possible use of OCT in screening of patients at risk for macular toxicity is
      suggested.

PMID- 25391071
TI  - Plasmin-assisted vitrectomy for bilateral combined hamartoma of the retina and
      retinal pigment epithelium: histopathology, immunohistochemistry, and optical
      coherence tomography.
AB  - PURPOSE: To report the surgical outcome, histopathology, immunohistochemistry,
      and optical coherence tomographic findings in a case of bilateral combined
      hamartoma of retina and retinal pigment epithelium. METHOD: Bilateral
      heterologous plasmin-assisted lens-sparing vitrectomy was performed. The surgical
      specimen underwent histopathological and immunohistochemical analysis. PATIENT:
      An 18-month-old male child with bilateral combined hamartoma of the retina and
      retinal pigment epithelium. RESULTS: After surgery, structural improvement
      (optical coherence tomography) and improved visual function were noted.
      Immunohistochemistry was positive for astrocytic markers and negative for others.
      DISCUSSION: Plasmin-assisted vitrectomy and membrane peeling in this child with
      bilateral combined hamartoma resulted in a marked improvement in the clinical and
      topographical appearance in both eyes and significantly improved visual function.
      The prospect of hamartoma recurrence is not a contraindication to surgical
      management. Immunohistochemically, the peeled epiretinal tissue showed
      characteristics of astrocytic origin providing insight into the possible source
      and structure of these membranes.

PMID- 25391072
TI  - Angioid streaks in thalassemia intermedia: warning for thromboembolic events.
AB  - PURPOSE: Pseudoxanthoma elasticum-like lesions have been described in association
      with an increased risk for stroke in beta-thalassemia. We describe a patient with
      thalassemia intermedia and angioid streaks who developed a central retinal artery
      occlusion and subsequent portal vein thrombosis. METHOD AND PATIENT: Case report
      of a 47-year-old woman with thalassemia intermedia, angioid streaks, central
      retinal artery occlusion, and portal vein thrombosis. RESULTS: Our patient
      presented with a cilioretinal artery-sparing central retinal artery occlusion in
      the left eye and evidence of angioid streaks in both eyes. One month later, she
      developed neovascularization of the angle in the left eye and underwent
      panretinal photocoagulation. Neovascularization of the angle resolved, and final
      vision was 20/30. She later developed portal vein thrombosis, and anticoagulation
      was started. CONCLUSION: The finding of angioid streaks in the setting of
      thalassemia may suggest the presence of a systemically defective elastin layer.
      This can be a procoagulative factor and may warrant further assessment of the
      coagulation and cardiovascular system to take prophylactic measures. The
      occurrence of a thromboembolic event, however, is multifactorial and the end
      result of interaction of procoagulant and anticoagulant factors.

PMID- 25391073
TI  - Purtscher-like retinopathy associated with primary hypereosinophilic syndrome.
AB  - PURPOSE: To describe a patient with undiagnosed primary hypereosinophilic
      syndrome (HES) who presented with Purtscher-like retinopathy and to review the
      literature. METHODS: Observational case report. PATIENT: A 25-year-old man
      presented with a 1-week history of bilateral visual blur. Examination revealed
      multiple peripapillary cotton-wool spots and few intraretinal hemorrhages.
      Clinical history was obtained and fluorescein angiography, systemic evaluation,
      laboratory studies, and histopathologic analysis of a bone marrow biopsy specimen
      were performed. RESULTS: The patient was diagnosed with primary HES. No previous
      description was found in the literature. CONCLUSION: HES should be considered in
      the differential diagnosis of Purtscher retinopathy. This case supports the
      microembolic theory of Purtscher retinopathy.

PMID- 25391074
TI  - Multicentric castleman disease with ocular involvement: a clinicopathologic case
      report.
AB  - PURPOSE: To describe an ocular manifestation of Castleman disease, a rare
      lymphoproliferative disorder characterized by sheets of abundant plasma cells in
      the interfollicular spaces of lymph nodes, most commonly in the abdomen,
      mediastinum, and cervical chain. METHODS: Clinicopathologic case report. PATIENT:
      A 69-year-old man with lymphadenopathy and bilateral choroidal infiltrates.
      RESULTS: Initially, we suspected systemic lymphoma with ocular involvement. Lymph
      node biopsy revealed Castleman disease without a monoclonal component. Choroidal
      biopsy showed lymphocytic and plasma cell infiltration. CONCLUSION: To our
      knowledge, this is the first clinicopathologic report of multicentric Castleman
      disease involving the eye.

PMID- 25391075
TI  - Exudative retinal detachment in castleman disease.
AB  - PURPOSE: To describe the course of a case of Castleman disease (CD) that
      presented with visual symptoms and retinal disease. METHODS: Clinical
      examination, fundus photography, and fluorescein and indocyanine green
      angiography were used to characterize the presence of bilateral exudative retinal
      detachments in a patient who was subsequently identified as having systemic
      lymphadenopathy. RESULTS: After an extensive medical workup including CT scans,
      blood testing, and a lymph node and renal biopsy, the patient was diagnosed with
      CD. Steroids were administered to treat CD. During the course of treatment, the
      patient developed renal failure, which was successfully treated with
      plasmapheresis. Four weeks later, the bilateral retinal detachments had resolved
      without local treatment. CONCLUSION: Exudative retinal detachments as
      manifestations of CD may be observed under systemic treatment for resolution
      before considering local therapy.

PMID- 25391076
TI  - Chorioretinitis and panuveitis in an infant with systemic langerhans cell
      histiocytosis.
AB  - BACKGROUND: Panuveitis and chorioretinitis in infants with Langerhans cell
      histiocytosis are rare and fundus photographic documentation is lacking in the
      literature. METHODS: Case report with fundus photography. RESULTS: The authors
      report a case of an infant with disseminated Langerhans cell histiocytosis who
      presented with panuveitis in the right eye and chorioretinitis in left eye.
      Treatment with chemotherapy led to resolution of chorioretinal lesions; however,
      the visual prognosis remained guarded because of the macular involvement and
      amblyopia. CONCLUSION: The authors recommend examination of infants with
      Langerhans cell histiocytosis for chorioretinal involvement.

PMID- 25391077
TI  - Chorioretinitis associated with weber-christian disease.
AB  - PURPOSE: To report the association between Weber-Christian disease and an
      intraocular inflammation. METHODS: Case report. RESULTS: We report the case of a
      62-year-old woman who presented with a granulomatous panuveitis and focal
      chorioretinitis accompanied by systemic signs of Weber-Christian disease, which
      is an idiopathic relapsing nodular panniculitis, confirmed by a biopsy showing a
      lobular panniculitis in a nodule of the arm. The evolution was favorable under
      long-term oral prednisolone administration. CONCLUSION: Ocular involvement is a
      rare feature of Weber-Christian Disease. Neverthless, fat tissue examination
      should be considered in presence of an ocular inflammation of unknown origin and
      a skin biopsy can be helpful in this context.

PMID- 25391078
TI  - MACULAR HOLE FORMATION AND CLOSURE AFTER CATARACT EXTRACTION AND Nd:YAG
      CAPSULOTOMY IN A VITRECTOMIZED EYE WITH AN EPIRETINAL MEMBRANE.
AB  - BACKGROUND: Vitreomacular traction and degeneration of the inner retinal layers
      of the fovea are considered contributing factors to idiopathic macular hole (MH)
      formation. This case report illustrates a rare scenario of MH formation and
      spontaneous closure associated with an epiretinal membrane (ERM) and perifoveal
      cystoid edema without anteroposterior traction from the vitreous in a previously
      vitrectomized eye. METHODS: A case report following MH clinical progression with
      visual acuity and serial optical coherence tomography. RESULTS: A 47-year-old
      high myope underwent scleral buckle placement and pars plana vitrectomy for a
      macula-off, phakic, inferior retinal detachment with a giant retinal tear and
      proliferative vitreoretinopathy 2.5 years ago with eventual visual acuity of
      20/20. Postoperatively, an ERM developed, and uncomplicated phacoemulsification
      cataract extraction was later performed. One week after Nd:YAG capsulotomy, a
      full-thickness MH formed (with perifoveal cystoid macular edema) that
      spontaneously resolved 2 months later with return of vision to 20/20. CONCLUSION:
      After vitrectomy, anteroposterior vitreofoveal traction no longer contributes to
      MH formation. Perifoveal cystoid macular edema as well as tangential traction
      from ERMs may contribute to MH formation.

PMID- 25391079
TI  - Pars plana vitrectomy from a temporal approach for a patient with a deep orbit.
AB  - PURPOSE: To present an alternate technique for safely performing pars plana
      vitrectomy (PPV) for patients with extremely deep-set eyes or prominent brow
      ridges. PATIENT AND METHODS: A single patient with a very deep orbit and severe
      glaucoma that limited the surgeon's ability to operate on the superior
      conjunctiva underwent 25-gauge PPV with the surgeon seated temporally. RESULTS:
      Twenty-five-gauge PPV with epiretinal membrane peeling and intraocular lens
      suturing was performed safely. CONCLUSION: PPV can be performed from a temporal
      approach if the access to the superior conjunctiva is limited.

PMID- 25391080
TI  - SUBCONJUNCTIVAL INTERFERON alpha-2A APPLICATION IN A CASE WITH SERPIGINOUS
      CHOROIDOPATHY.
AB  - BACKGROUND: Serpiginous choroidopathy (SC) is a chronic, inflammatory disease
      which progresses with recurrences leading to visual loss. Diverse
      immunosuppressive regimens have been used for treatment. In case of an
      unanticipated side effect with immunosuppressive agents, alternative modalities
      in SC are limited. METHODS: A 38-year-old woman presented with slight
      deterioration in visual acuity in her right eye. She had had a visually
      devastating episode of SC in the left eye 8 months previously. She received
      combination therapy of prednisone, cyclosporine, and intravitreal triamcinolone
      for the left eye. With that treatment, vision in her left eye declined to light
      perception due to macular involvement and renal functions were impaired. Eight
      months later, she was hospitalized with the diagnosis of SC in the right eye. In
      the quest for an alternative modality, a combination of antituberculosis
      medications was given initially, because of the high PPD reading. Despite 10 days
      of treatment, the lesion persistently progressed. Subsequently, interferon (INF)
      alpha-2a therapy was initiated solely as daily injections of 1 million unit (MIU)
      subconjunctivally. The frequency of injections was tapered within the course.
      Currently, injections are still being dispensed once a month. RESULTS: Throughout
      the 12 months of follow-up, the patient had no major side effects due to INF
      alpha-2a therapy. At present, SC in the right eye is inactive and the macula is
      safe in terms of incurring. The vision is 20/20 in the right eye, whereas it is
      light perception in the left eye. CONCLUSION: Interferon alpha-2a administration
      in SC can be an efficient modality and is free of immunosuppression related side
      effects. Subconjunctival application seems to be a promising and safe tool for
      treatment.

PMID- 25391081
TI  - Photodynamic therapy of bullous central serous chorioretinopathy with subretinal
      exudate and a tear of the retinal pigment epithelium.
AB  - PURPOSE: To report a case of bullous central serous chorioretinopathy associated
      with subretinal exudates and a tear of the retinal pigment epithelium imaged
      using spectral domain optical coherence tomography and treated successfully with
      reduced fluence verteporfin photodynamic therapy. PATIENTS: Observational case
      report. METHODS: Patient with central serous chorioretinopathy and associated
      subretinal exudates was imaged using spectral domain optical coherence tomography
      and managed using photodynamic therapy. RESULTS: The patient was treated
      unsuccessfully with intravitreal bevacizumab and ranibizumab followed by
      successful treatment with reduced fluence photodynamic therapy. Spectral domain
      optical coherence tomography imaging of the lesion identified the subretinal
      exudates and a retinal pigment epithelium tear before treatment. CONCLUSION: In
      this case of severe bullous central serous chorioretinopathy, spectral domain
      optical coherence tomography identified a tear of the retinal pigment epithelium
      not previously identified using clinical exam or time domain optical coherence
      tomography. The lesion was successfully treated using reduced fluence
      photodynamic therapy after intravitreal antivascular endothelial growth factor
      drugs had no effect.

PMID- 25391082
TI  - Central serous chorioretinopathy and peripheral retinal neovascularization.
AB  - PURPOSE: To report a case of bullous retinal detachment complicated by peripheral
      retinal ischemia and neovascularization in a patient with chronic central serous
      chorioretinopathy (CSC). RESULTS: Focal laser photocoagulation to the active
      retinal pigment epithelial leaks in the posterior pole resulted in resolution of
      the bullous detachment and regression of the retinal neovascularization.
      CONCLUSIONS: Patients with chronic CSC and a large, dependent serous detachment
      with peripheral retinal ischemia and neovascularization may be managed by focal
      treatment to active pigment epithelial leaks alone. This could spare patients of
      the adverse effects associated with widespread laser treatment and reduce the
      risk of visual loss due to vitreous hemorrhage and/or more severe complications
      resulting from progressive retinal ischemia.

PMID- 25391083
TI  - Live intraocular dirofilaria causing multifocal choroiditis.
AB  - PURPOSE: To report a rare case of live intraocular Dirofilaria causing anterior
      uveitis and multifocal choroiditis. METHOD: Observational case report. RESULT: A
      43-year-old, healthy, Asian Indian woman presented with complaints of pain,
      redness, floaters, and decreased vision in the right eye. Slit lamp examination
      revealed a vigorously moving live intraocular worm in the anterior chamber.
      Indirect ophthalmoscopy showed active multifocal choroiditis in the posterior
      pole with retinal pigment epithelial tracts and chorioretinal scars in the
      periphery. Surgical removal of the worm from the anterior chamber was done
      immediately. The patient was then treated with diethylcarbamazine citrate along
      with topical steroids. CONCLUSION: In endemic countries, in a patient with
      multifocal choroiditis, one should look for retinal pigment epithelial tracts in
      the retina to rule out parasitic infestation like Dirofilaria. Careful
      examination, prompt diagnosis, and early treatment can reduce ocular morbidity.

PMID- 25391084
TI  - Pituitary adenoma presenting as bilateral bullous exudative retinal detachments:
      a clinicopathologic report.
AB  - PURPOSE: To describe a case of pituitary adenoma presenting as bilateral serous
      retinal detachments and the histopathologic and hematologic evidence of a
      linkage. METHODS: Record review for a single patient including testing to
      determine the etiology of the retinal detachments. RESULTS: The retinal
      detachments were determined to be a variant of central serous chorioretinopathy.
      A pituitary adenoma was discovered by neuroimaging. Histopathologic analysis of
      the tumor and serum cortisol levels demonstrated the lesion to be a cortisol
      secreting adenoma. CONCLUSION: Bilateral serous retinal detachments are a variant
      of central serous chorioretinopathy and a rare presentation of pituitary adenoma.

PMID- 25391085
TI  - Effects of terminal dimethylation and metal coordination of proline-2
      formylpyridine thiosemicarbazone hybrids on lipophilicity, antiproliferative
      activity, and hR2 RNR inhibition.
AB  - The nickel(II), copper(II), and zinc(II) complexes of the proline
      thiosemicarbazone hybrids 3-methyl-(S)-pyrrolidine-2-carboxylate-2-formylpyridine
      thiosemicarbazone (L-Pro-FTSC or (S)-H2L(1)) and 3-methyl-(R)-pyrrolidine-2
      carboxylate-2-formylpyridine thiosemicarbazone (D-Pro-FTSC or (R)-H2L(1)), as
      well as 3-methyl-(S)-pyrrolidine-2-carboxylate-2-formylpyridine 4,4-dimethyl
      thiosemicarbazone (dm-L-Pro-FTSC or (S)-H2L(2)), namely, [Ni(L-Pro-FTSC-2H)]2
      (1), [Ni(D-Pro-FTSC-2H)]2 (2), [Ni(dm-L-Pro-FTSC-2H)]2 (3), [Cu(dm-L-Pro-FTSC
      2H)] (6), [Zn(L-Pro-FTSC-2H)] (7), and [Zn(D-Pro-FTSC-2H)] (8), in addition to
      two previously reported, [Cu(L-Pro-FTSC-2H)] (4), [Cu(D-Pro-FTSC-2H)] (5), were
      synthesized and characterized by elemental analysis, one- and two-dimensional
      (1)H and (13)C NMR spectroscopy, circular dichroism, UV-vis, and electrospray
      ionization mass spectrometry. Compounds 1-3, 6, and 7 were also studied by single
      crystal X-ray diffraction. Magnetic properties and solid-state high-field
      electron paramagnetic resonance spectra of 2 over the range of 50-420 GHz were
      investigated. The complex formation processes of L-Pro-FTSC with nickel(II) and
      zinc(II) were studied in aqueous solution due to the excellent water solubility
      of the complexes via pH potentiometry, UV-vis, and (1)H NMR spectroscopy. The
      results of the antiproliferative activity in vitro showed that dimethylation
      improves the cytotoxicity and hR2 RNR inhibition. Therefore, introduction of more
      lipophilic groups into thiosemicarbazone-proline backbone becomes an option for
      the synthesis of more efficient cytotoxic agents of this family of compounds.

PMID- 25391086
TI  - ACSM clinician profile. Anthony C. Luke, MD, MPH, FACSM.

PMID- 25391087
TI  - Fatal caffeine overdose and other risks from dietary supplements.

PMID- 25391089
TI  - Infraspinatus atrophy in a volleyball player: a case of a bennett lesion causing
      nerve impingement.

PMID- 25391090
TI  - Effects of excessive endurance activity on the heart.
AB  - Regular moderate exercise confers many cardiovascular and health benefits.
      Because of this, endurance sports events have become very popular with
      participation increasing tremendously over the past few years. In conjunction
      with this increase in popularity and participation, people also have increased
      the amount that they exercise with many training for and competing in
      ultraendurance events such as ultradistance running events, iron distance
      triathlons, or multiday races. This excess endurance activity may appear to
      increase the risk of cardiac abnormalities, which may increase the risk for long
      term morbidity or mortality. While it is known that moderate exercise has
      benefits to cardiovascular health, ultimately, the long-term cardiac effects of
      excessive endurance activity are unclear. What is clear, however, is that
      moderate exercise is beneficial, and to date, the evidence does not support
      recommending against physical activity. 

PMID- 25391091
TI  - The million dollar question: When should an athlete retire after concussion?
AB  - Management of acute concussions is guided by consensus statement, and the return
      to-play process begins when an athlete's symptoms and examination return to
      baseline. This process may be relatively clear if symptoms resolve within the
      normal time frame following a first or second concussion. This decision-making
      process is more complicated in an athlete with prolonged unresolved symptoms,
      multiple concussions both with and without prolonged recovery, or a structural
      brain injury. In these situations, determining when to retire an athlete after
      concussion is a complex decision, without available evidence-based guidelines.
      This article will discuss absolute and relative contraindications to returning an
      athlete to contact sport following a concussion in three separate scenarios:
      following potentially life-threatening brain injury, persistent clinical symptoms
      or signs of prolonged postconcussion syndrome, and multiple concussions but
      without residual symptoms or signs. 

PMID- 25391092
TI  - Diagnostic considerations of lateral column foot pain in athletes.
AB  - Foot maladies are often classified descriptively by general foot locations, i.e.,
      forefoot, midfoot, and rearfoot. However, common vernacular verbiage, implicating
      a common biomechanical purpose, also applies pathology to the medial or lateral
      foot column. Although imprecisely defined, lateral column injuries to the foot
      encompass conditions that affect any of the lateral side of the foot from the
      calcaneus to the toes. The lateral column of the foot includes the calcaneus, the
      cuboid, the fourth and fifth metatarsals as well as the calcaneocuboid, cuboido
      metatarsal, and intermetatarsal joints. It may be helpful to think in a "lateral
      column" fashion when evaluating and treating certain lateral foot injuries, load
      patterns, and biomechanical or anatomical faults. Misdiagnosed injuries in this
      area of the foot can be a source of great morbidity to the athlete. It is
      important for the clinician to be aware of common conditions presenting as pain
      to the lateral side of the foot. 

PMID- 25391093
TI  - Injuries in women's ice hockey: special considerations.
AB  - Ice hockey is a popular collision sport with a growing number of female athletes
      participating each year. As participation among girls and women continues to
      increase, it will be important to recognize common injuries occurring during
      women's games. Despite difference in the rules that prohibit body checking in
      women's and girls' games, injury profiles are similar to those of their male
      counterparts. Concussions, contusions, acromioclavicular joint injuries,
      ligamentous knee injuries, and muscle strains occur during women's ice hockey
      games, with groin strains accounting for the most common practice injury. This
      article will review both injury rates and common injuries occurring in women's
      ice hockey, with a focus on the observed concussion rate and groin injuries. 

PMID- 25391094
TI  - Hip pain in dancers.
AB  - Dancers require extreme ranges of motion in their hips. They require this for
      many styles and performances. Hip pain and hip injury in dancers can lead to lost
      work and performance time. There are many potential causes for hip pain in the
      dancer, including dysplasia, hyperlaxity, both intra- and extra-articular
      impingement, and soft tissue injuries. This article will review the current
      literature on these topics in dancers and how they can be applied to the dancer
      patient. 

PMID- 25391095
TI  - Young age as a modifying factor in sports concussion management: what is the
      evidence?
AB  - In 2008, the Concussion in Sport Group (CISG) published its third consensus
      statement and introduced 10 'modifying' factors that were presumed clinically to
      influence the investigation and management of concussions in sports. Young age
      was listed as one of the modifying factors. In some cases, these modifiers were
      thought to be predictive of prolonged or persistent symptoms. These same
      modifying factors were retained in the fourth iteration of the CISG consensus
      statement (2013), although mention was made of possible limitations of their
      efficacy. The CISG statements provided several empirical references regarding
      young age as a modifying factor. We reviewed the published sports concussion
      literature with the purpose of determining empirical studies that support or
      refute the inclusion of young age as a modifier of concussive injury in sports.
      We performed a systematic review of the PubMed database utilizing the keywords
      concussion, sports, mild traumatic brain injury, youth, adolescents, and
      children. English language studies were extracted by the authors and summarized
      for review. Multiple empirical studies were found indicating that younger
      athletes may take longer to recover from a sports-related concussion (SRC) than
      their older peers. However, studies did not indicate that younger athletes were
      at more risk for prolonged recovery (>4 wk). Empirical evidence supports the
      inclusion of young age as a modifying factor in sports concussion. However, the
      difference in recovery time seems relatively small (a few days) and young age
      does not predict prolonged recovery (>4 wk). The findings support the inclusion
      of young age as a specific modifier in the treatment of SRC and have implications
      for the clinical management of this common injury. 

PMID- 25391096
TI  - Advancing the preparticipation physical evaluation (PPE): an ACSM and FIMS joint
      consensus statement.
AB  - While the preparticipation physical evaluation (PPE) is widely accepted, its
      usage and content are not standardized. Implementation is affected by cost,
      access, level of participation, participant age/sex, and local/regional/national
      mandate. PPE screening costs are generally borne by the athlete, family, or club.
      Screening involves generally agreed-upon questions based on expert opinion and
      tested over decades of use. No large-scale prospective controlled tracking
      programs have examined PPE outcomes. While the panel did not reach consensus on
      electrocardiogram screening as a routine part of PPE, all agreed that a history
      and physical exam focusing on cardiac risk is essential, and an ECG should be
      used where risk is increased. The many areas of consensus should help the
      American College of Sports Medicine and the Federation Internationale du Medicine
      du Sport in developing a universally accepted PPE. An electronic PPE, using human
      centered design, would be comprehensive, would provide a database given that PPE
      is mandatory in many locations, would simplify PPE administration, would allow
      remote access to clinical data, and would provide the much-needed data for
      prospective studies in this area. 

PMID- 25391100
TI  - High-penetration optical coherence tomography and enhanced depth imaging in
      presumed retinal pigment epithelial hamartoma.
AB  - PURPOSE: To report on high-penetrating swept source optical coherence tomography
      (SS-OCT) imaging and enhanced depth imaging in an eye with presumed retinal
      pigment epithelial hamartoma . METHODS AND PATIENTS: A 60-year-old man with
      presumed retinal pigment epithelial hamartoma underwent complete ophthalmologic
      examination, including fluorescein angiography, indocyanine green angiography,
      enhanced depth imaging OCT, and SS-OCT. RESULTS: In the left eye, there were six
      darkly pigmented, nodular, circumscribed lesions in the macular area. The margins
      were well defined and were not associated with changes such as edema, exudation,
      or hemorrhage. Fluorescein angiography revealed a minimally dilated feeding
      artery and draining vein in each lesion. Spectral domain OCT demonstrated an
      elevation of the retina at the site of the lesions with greatly enhanced optical
      reflectivity of the inner surface and complete shadowing of optical transmission
      with crisp vertical margins. However, enhanced depth imaging OCT and SS-OCT
      revealed deeper retinal layer structures in the pigmented lesions. Intraretinal
      lesions showed superficial involvement and preretinal extension with or without
      superficial hyporeflective regions. CONCLUSION: Enhanced depth imaging OCT and SS
      OCT revealed deeper retinal layer structures in the pigmented lesions in a case
      with presumed retinal pigment epithelial hamartoma. Enhanced depth imaging OCT
      and SS-OCT are useful for visualization of intraretinal structures in these
      lesions, leading to further investigation of the origin and development of
      retinal pigment epithelial hamartoma.

PMID- 25391101
TI  - Traction retinal detachment under silicone oil treated with two-port, 25-gauge
      pars plana vitrectomy and scissor segmentation in a child with familial exudative
      vitreoretinopathy.
AB  - PURPOSE: To describe a method of 25-gauge pars plana vitrectomy (PPV) with
      posterior hyaloid scissor segmentation in a child with recurrent retinal
      detachment caused by vitreous traction under silicone oil. METHODS: A two-port,
      25-gauge PPV was performed under previously instilled silicone oil with
      retinotomy and internal drainage of subretinal fluid. RESULTS: A 5-year-old
      monocular girl with familial exudative vitreoretinopathy presented with decreased
      vision and a recurrent retinal detachment 3 weeks after PPV and air-silicone
      exchange for rhegmatogenous retinal detachment. Ophthalmoscopy, fundus
      photography, and optical coherence tomography revealed persistent posterior
      hyaloid adherent to multiple retinal foci inducing a tractional detachment. The
      patient underwent two-port PPV revision with scissor segmentation of vitreous
      traction. Follow-up examination at 3 months revealed the absence of vitreous
      traction, an attached retina, and markedly improved vision. CONCLUSION: Posterior
      vitreous sequestered under silicone oil inducing consecutive retinal detachment
      may be successfully managed with two-port interface PPV and scissor segmentation
      of vitreous traction.

PMID- 25391102
TI  - Retrobulbar gas after macular hole surgery: a case report.
AB  - PURPOSE: To present a case of a patient who underwent vitreoretinal surgery for
      repair of a full-thickness macular hole and received an inappropriate
      concentration of C3F8 gas. METHODS: Interventional case report. RESULTS: A 63
      year-old man with a Stage IV full-thickness macular hole underwent uneventful
      macular hole surgery. The vitreous cavity was filled with presumed 16%
      perfluoropropane (C3F8) gas and none of the sclerotomies were sutured closed.
      Postoperatively, the patient presented with severe pain and proptosis and a
      visual acuity of count fingers. His condition was managed initially with a
      vitreous gas tap after which an emergency computed tomography was performed
      revealing retrobulbar air. The patient returned to the operating room and
      underwent surgical decompression of the retrobulbar gas. Despite medical
      management to manage his intraocular pressure, the patient required a second
      vitreous tap. By Postoperative Day 10 after his original macular hole surgery,
      the gas fill of the posterior segment started to decrease, his proptosis had
      resolved, and his pain had diminished. By Postoperative Day 60, the macular hole
      closed and the optic nerve exhibited no pallor or cupping. CONCLUSION: Despite an
      inappropriate concentration of gas being used, the unsutured sclerotomies allowed
      escape of the gas from the vitreous space, buffering the rise in intraocular
      pressure and preventing complete vascular occlusion.

PMID- 25391103
TI  - Tissue remodeling in a surgically repaired macular hole.
AB  - PURPOSE: The authors report a case with early reopening, spontaneous closure, and
      delayed reopening with optical coherence tomography after successful repair to
      highlight the dynamic nature of tissue remodeling in surgically repaired macular
      holes. METHOD: Observational case report. RESULT: A 62-year-old woman underwent
      successful surgery for Grade IV macular hole. Five weeks postoperatively, the
      macular hole reopened but underwent spontaneous closure at 6 months of follow-up.
      Nine months later, there was reopening of the macular hole, which was surgically
      repaired. CONCLUSION: Successful macular hole repair warrants long-term
      observation due to the ongoing tissue remodeling.

PMID- 25391104
TI  - Purtscher-like retinopathy in association with metastatic pancreatic
      adenocarcinoma and capecitabine therapy.
AB  - PURPOSE: To report a case of Purtscher-like retinopathy in association with
      capecitabine chemotherapy for metastatic pancreatic adenocarcinoma. METHODS: Case
      report. RESULTS: Bilateral retinal hemorrhages and cotton-wool spots in a
      predominantly juxtapapillary distribution were observed coincident with decreased
      vision. There was gradual improvement of the retinopathy and patient's vision
      over several months until the time of death. CONCLUSION: Metastatic pancreatic
      cancer and capecitabine, a fluoropyrimidine chemotherapeutic agent, are a rare
      cause of Purtscher-like retinopathy.

PMID- 25391105
TI  - Features and surgical outcome of retinal nerve fiber layer alterations associated
      with epiretinal membrane.
AB  - PURPOSE: In this study, the authors aimed to investigate structural abnormalities
      in the retinal nerve fiber layer (RNFL) using spectral-domain optical coherence
      tomography (SD-OCT) and study the surgical outcomes in eyes with such alterations
      by comparing ultrastructure findings of the surgically excised epiretinal
      membrane (ERM) and inner limiting membrane (ILM) in patients with idiopathic ERM.
      METHODS AND PATIENTS: Vitreous surgery was performed on four eyes with idiopathic
      ERM, of which three had columnar alterations of the nerve fiber layer. The ERM
      and ILM were dissected and removed, and ultrathin sections were analyzed and
      imaged completely by using electron microscopy. All the patients underwent a
      comprehensive ophthalmologic examination, including SD-OCT, fundus-monitoring
      microperimetry, and red-free scanning laser ophthalmoscopic imaging. RESULTS:
      Preoperatively, SD-OCT revealed the presence of columnar structures only in the
      RNFL. Transmission electron microscopy showed that all samples contained retinal
      cell debris on the outer surface of the ILM. However, adhesion of retinal nerve
      fibers on the outer surface of the ILM was not observed in any specimen. The
      columnar alterations in the RNFL observed via SD-OCT resolved completely within 1
      month in all eyes. At 6 months after surgery, no eyes showed scotoma on
      microperimetry. Further, no dissociated nerve fiber layer appearance was
      identified. CONCLUSION: Vitrectomy with ILM peeling can be safely performed for
      ERMs with RNFL alterations, detected preoperatively by SD-OCT, without any
      structural or functional disturbances. The columnar alterations of the RNFL on SD
      OCT may be inner retinoschisis.

PMID- 25391106
TI  - Bevacizumab presurgical treatment for proliferative sickle-cell retinopathy
      related retinal detachment.
AB  - PURPOSE: To report the use of presurgical intravitreal bevacizumab in the context
      of proliferative sickle-cell retinopathy with retinal detachment. METHODS:
      Intravitreal bevacizumab was injected 3 days before the surgical procedure for
      traction retinal detachment. Vitrectomy, membrane peeling, endolaser, and SF6 gas
      tamponade were performed. A 37-year-old African American woman presented with
      hemoglobin sickle-cell disease and temporal retinal detachment with bullous
      subretinal fluid extending through the fovea associated with an area of active
      sea-fan retinal neovascularization with preretinal hemorrhage and retinal
      traction, with 3 associated retinal breaks. RESULTS: The sea-fan
      neovascularization associated with the traction retinal detachment and the
      resultant retinal breaks appeared more fibrotic and les vascular than was noted
      prior to the pre-operative bevacizumab injection. Segmentation and dissection
      were performed with minimal bleeding, and retinal traction was relieved without
      difficulty. This was believed to be atypical in the experience of the surgeons.
      One month postoperatively, vision measured 20/50, and the retina remained
      attached. CONCLUSION: Further study is necessary to clarify the role of anti
      vascular endothelial growth factor in the treatment of proliferative sickle cell
      retinopathy associated retinal detachment.

PMID- 25391107
TI  - Delayed recurrent neovascularization and persistent avascular retina following
      intravitreal bevacizumab for retinopathy of prematurity.
AB  - PURPOSE: Intravitreal bevacizumab is becoming increasingly popular in the
      treatment of retinopathy of prematurity. Ophthalmologists should be aware of
      potential complications and failures of this treatment. METHODS: Case report and
      literature review. RESULTS: A premature infant born at 23 weeks gestational age
      developed zone 1 stage 3 retinopathy of prematurity with plus disease in both
      eyes. At 36 weeks postmenstrual age, the patient was treated with intravitreal
      bevacizumab and the neovascularization initially regressed. However, the
      patient's peripheral avascular retina persisted and at 53 weeks postmenstrual
      age, the patient developed recurrent neovascularization and plus disease of both
      eyes requiring treatment with laser photocoagulation. The infant showed
      regression of neovascularization and improvement of plus disease after laser, but
      contraction of fibroglial tissue caused a tractional retinal detachment. The
      retina was successfully reattached after pars plana vitrectomy and membrane peel.
      CONCLUSION: Infants receiving intravitreal bevacizumab as primary treatment for
      retinopathy of prematurity can show initial regression of neovascularization with
      delayed recurrence of neovascularization and persistence of peripheral avascular
      retina greater than 4 months after initial treatment. Ophthalmologists following
      infants with retinopathy of prematurity treated with intravitreal bevacizumab
      should be aware of the possibility of delayed recurrent neovascularization and
      subsequent complications.

PMID- 25391108
TI  - Embolus-induced branch retinal artery occlusion with a presenting best-corrected
      visual acuity of <6/12 and visual field defect: yag embolectomy safely restores
      arteriolar perfusion and/or visual function.
AB  - PURPOSE: To study the effects of translumenal Nd:YAG embolectomy (TYE) on the
      visual functions of patients presenting with decreased vision (<6/12) and visual
      field defect (VFD) from embolus-induced branch retinal artery occlusions.
      METHODS: Case reports. RESULTS: The initial information available for five
      Chinese patients consisted of best-corrected visual acuity, visual field, and the
      branch retinal artery embolus location/laterality. These consisted of Case 1
      (6/15; 3-day upper VFD; temporal lower first bifurcation; left eye), Case 2
      (6/120; 1-week upper VFD; macular edema; disk; right eye), Case 3 (6/30; 1-week
      upper VFD; temporal lower first bifurcation; left eye), Case 4 (6/60; 1-day lower
      VFD; temporal upper first bifurcation; left eye), and Case 5 (counting finger;
      temporal upper first bifurcation; left eye). In all five cases, a fluorescein
      angiogram showed delayed arteriolar filling. At approximately 2 weeks after a
      single TYE treatment (Cases 1, 3, and 5) or a double TYE treatment (Case 4),
      fluorescein angiogram showed restoration of arteriolar perfusion. Furthermore,
      the patients' visual field and MP-1 sensitivity reductions were attenuated in
      Cases 1, 3 and 4, and their best-corrected visual acuities had improved to 6/10
      (Case 1), 6/7.5 (Case 3), 6/6 (Case 4), and 6/60 (Case 5). In Case 2, 2 TYE
      treatments combined with Avastin and Kenacort also improved her situation despite
      persistent macular edema with the best-corrected visual acuity further increasing
      to 6/7.5. CONCLUSION: Conclusively, TYE is a safe and effective procedure that
      can be used to treat eyes with embolus-induced branch retinal artery occlusion
      with a presenting best-corrected visual acuity of <6/12 and visual defect.

PMID- 25391109
TI  - Effect of intravitreal dexamethasone implant on the contralateral eye: a case
      report.
AB  - PURPOSE: To describe the effect of unilateral intravitreal injection of 0.7-mg
      dexamethasone implant on the other eye. METHODS: Interventional case report and
      literature review. RESULTS: A 54-year-old woman with bilateral, refractory,
      clinically significant macular edema was given an intravitreal injection of 0.7
      mg dexamethasone sustained release implant in the right eye. The central foveal
      thickness improved in both the eyes with recurrence of edema after 16 weeks in
      both the eyes. CONCLUSION: An intravitreal dexamethasone injection seems to have
      bilateral effect after unilateral injection.

PMID- 25391110
TI  - Intravitreous ranibizumab for persistent macular edema in retinal vein occlusion
      unresponsive to bevacizumab.
AB  - PURPOSE: To report successful treatment of persistent retinal edema associated
      with retinal vascular occlusion with ranibizumab after initial failure with
      bevacizumab intravitreal injections. METHODS: A retrospective chart review of all
      patients undergoing treatment with intravitreal bevacizumab for retinal vascular
      occlusion was undertaken. Clinical features of patients who were switched to
      monthly ranibizumab because of persistent and/or worsening retinal edema despite
      multiple (six or more) monthly intravitreal bevacizumab injections were selected
      for review. The type of retinal vascular occlusion, age of the patient, visual
      acuity at each visit, number of intravitreal bevacizumab injections, optical
      coherence tomography findings at each visit, fluorescein angiography, and number
      of intravitreal ranibizumab injections with optical coherence tomography findings
      at each subsequent visit were recorded. RESULTS: Six patients (five women and one
      man) were identified. Age ranged from 56 years to 74 years. Five had central
      retinal vein occlusion and one a branch retinal vein occlusion. All were treated
      with at least 6 sequential intravitreal bevacizumab injections (range, 6-13)
      before treatment with ranibizumab. All demonstrated an immediate and marked
      reduction in retinal edema that had not occurred with any of the previous
      treatments. The average central foveal thickness on optical coherence tomography
      was 592 um before ranibizumab injection and 346 um after the injection. Visual
      acuity improved in four of the six patients and was stable in the remaining two
      patients. CONCLUSION: Eyes of patients with persistent macular edema secondary to
      retinal vein occlusion despite bevacizumab may experience prompt improvement
      after initiation of intravitreal ranibizumab injections.

PMID- 25391111
TI  - Fulminant chorioretinitis and papillitis secondary to coxsackievirus B presenting
      as acute posterior multifocal placoid pigment epitheliopathy with positive
      response to intravenous immunoglobulin.
AB  - PURPOSE: To describe a case of fulminant bilateral papillitis and chorioretinitis
      in the setting of positive coxsackievirus B titers, which convalesced months
      after the patient's presentation. The patient presented with an acute posterior
      multifocal placoid pigment epitheliopathy-like clinical picture and her visual
      acuity and visual field improved moderately after initiation of treatment with
      intravenous immunoglobulin. METHODS: Case report of a white female with bilateral
      blurred vision is presented in this study. RESULTS: A previously healthy 59-year
      old white woman presented with a 3-day history of bilateral blurred vision.
      Initial visual acuity was hand motion in the right eye and count fingers in the
      left eye. Extensive workup and imaging was done and she was empirically started
      on intravenous antibiotics followed 24 hours later by intravenous steroids. The
      patient was found to have high titers of coxsackievirus B and sustained modest
      visual acuity and perimetry improvement in one eye after intravenous
      immunoglobulin infusion. CONCLUSION: A case of fulminant bilateral
      chorioretinitis and papillitis that resulted in bilateral vision loss despite
      high-dose steroids within 24 hours of initial loss in vision is presented in this
      study. The patient was found to have high titers of coxsackievirus B3, B4,B5
      after presentation and her condition improved after treatment with intravenous
      immunoglobulin, suggesting a plausible immune component.

PMID- 25391112
TI  - Spectral-domain optical coherence tomography of roth spots.
AB  - PURPOSE: To describe the retinal findings of subacute bacterial endocarditis,
      their evolution after treatment, and analysis with spectral-domain optical
      coherence tomography. METHODS: Retrospective chart review. RESULTS: A 21-year-old
      man presented with the sudden onset of a central scotoma in his left eye because
      of a sub-internal limiting membrane hemorrhage overlying the left fovea. When
      examined 2 weeks later, Roth spots were noted in his right eye. The patient was
      immediately referred to his internist and diagnosed with subacute bacterial
      endocarditis with cultures positive for Streptococcus viridans. He subsequently
      underwent aortic valve replacement surgery after 4 weeks of intravenous
      antibiotic therapy. When examined 4 weeks after valve replacement surgery, there
      was regression of the Roth spots. CONCLUSION: The present case demonstrates the
      importance of a funduscopic examination in the early diagnosis and management of
      subacute bacterial endocarditis. The analysis of Roth spots with spectral-domain
      optical coherence tomography suggested that they were septic emboli.

PMID- 25391113
TI  - Serous retinal detachments associated with light chain deposition disease.
AB  - PURPOSE: To report the clinical, fluorescein angiography, spectral-domain optical
      coherence tomography, and fundus autofluorescence (AF) findings of a 64-year-old
      woman with systemic light chain deposition disease. METHODS: Clinical
      examination, fundus photographs, fundus AF, spectral-domain optical coherence
      tomography, and fluorescein angiography before and after renal transplantation in
      a patient with light chain deposition disease. RESULTS: The patient presented
      with decreased visual acuity in her right eye. Fundus examination showed
      bilateral drusenoid subretinal deposits associated with subretinal fluid.
      Fluorescein angiography showed staining of the lesions seen on clinical
      examination. Spectral-domain optical coherence tomography showed hyperreflective
      material below the neurosensory retina associated with subretinal fluid. Fundus
      AF showed areas of increased AF corresponding to the lesions. The lesions showed
      improvement after renal transplantation and initiation of immunosuppressive
      agents. CONCLUSION: Patients with light chain deposition disease may present with
      subretinal deposits that can be seen clinically and demonstrated on fluorescein
      angiography, AF, and optical coherence tomography. They may also present with
      localized serious retinal detachments. Both these deposits and serous retinal
      detachments may improve with renal transplantation or immunosuppressive therapy.

PMID- 25391114
TI  - Immediate hyphema after intravitreal injections of ranibizumab.
AB  - PURPOSE: To report two cases of immediate hyphema formation after the
      intravitreal injection of ranibizumab. METHODS: Retrospective case reports.
      RESULTS: A patient with choroidal neovascularization caused by exudative age
      related macular degeneration and a patient with cystoid macular edema caused by
      branch retinal vein occlusion underwent an intravitreal injection of 0.5 mg/0.05
      mL of ranibizumab. The development of hyphema was seen immediately after the
      intravitreal injection in both cases. One patient was pseudophakic, taking 325 mg
      of aspirin daily. The other patient was phakic without any anticoagulation
      history. CONCLUSION: To the best of our knowledge, this is the third report of
      the development of hyphema associated with intravitreal injections.

PMID- 25391115
TI  - Optical coherence tomography confirmed resolution of macular edema in a diabetic
      patient after hemodialysis.
AB  - PURPOSE: The authors report the first case, to their knowledge, of resolution of
      diffuse macular edema after hemodialysis, which has been confirmed by optical
      coherence tomography. METHODS: A 53-year-old white woman with type 2 diabetes
      developed worsening macular edema and was examined in the ophthalmology clinic
      and scheduled for macular grid laser photocoagulation. The laser, however, was
      deferred for 4 weeks because she had also developed end-stage renal failure and
      required hemodialysis. RESULTS: When she was reviewed in the ophthalmology clinic
      4 weeks later for laser therapy, it was found that her macular edema had
      resolved, vision had improved, and laser was unnecessary. Review at 6 months
      showed that the macular edema remains resolved. CONCLUSION: Ophthalmologists
      should be aware that hemodialysis may reduce macular edema in such patients.

PMID- 25391116
TI  - Complete visual recovery after incipient crao due to ocular hypoperfusion in a
      patient with moyamoya disease.
AB  - PURPOSE: The purpose of this study was to report a case of an impending central
      retinal artery occlusion with hypoperfusion in a moyamoya patient. METHODS: A
      young, surgically revascularized moyamoya patient experienced severe unilateral
      vision loss from 20/25 to hand motions because of impending central retinal
      artery occlusion. The patient was treated with a combination of intermittent
      ocular massage, intraocular pressure-lowering medications, and aspirin. PATIENTS:
      A case of a moyamoya patient at Stanford University Medical Center. RESULTS:
      Visual acuity was restored to baseline by improving the ocular arterial-venous
      gradient after prompt administration of ocular massage, intraocular pressure
      lowering drops, and aspirin. CONCLUSION: This dramatic result suggests that, if
      performed in a timely manner, augmentation of ocular perfusion can result in
      complete restoration of vision in some cases of incipient central retinal artery
      occlusion.

PMID- 25391117
TI  - Caterpillar setae penetration in an eye: long-term follow-up.
AB  - PURPOSE: To report the results of 9 years of follow-up after caterpillar setae
      penetration into a child's eye. METHODS: The clinical course of caterpillar setae
      penetrating an eye and their migration will be described. Initially confined to
      the anterior segment (conjunctiva, cornea), they later migrated to the anterior
      chamber and iris toward the posterior pole. Management included treatment of the
      associated recurrent uveitis and repeated surgical interventions including pars
      plana vitrectomy. PATIENTS: Ten-year-old boy at the time of the initial eye
      injury. RESULTS: It was not possible to completely remove the caterpillar setae
      that had penetrated the conjunctiva and cornea. Later attempts to remove the
      setae from the anterior chamber and the vitreous by pars plana vitrectomy were
      also unsuccessful. Argon laser photocoagulation was performed around the setae,
      which later reached the retina, but did not prevent their further migration.
      CONCLUSION: Management of an eye injury caused by caterpillar setae is
      problematic because they are almost impossible to remove from eye tissue. Setae
      have a tendency to migrate in the eye. It requires long-term follow-up,
      conservative management of recurrent uveitis, as well as repeated surgical
      interventions.

PMID- 25391118
TI  - Solid-appearing retinal cysts in diabetic macular edema: a novel optical
      coherence tomography finding.
AB  - PURPOSE: To describe a novel finding of solid-appearing retinal cysts in patients
      with diabetic macular edema. METHODS: Case series of four patients with diabetic
      retinopathy discovered to have solid-appearing retinal cysts on spectral-domain
      optical coherence tomography. RESULTS: These cases demonstrate the presence of
      inner retinal hyporeflective cysts filled with an isoreflective substance on
      spectral-domain optical coherence tomography. These solid-appearing cysts arise
      from previously fluid-filled cysts and are not found in relation to intraretinal
      hemorrhage. Treatment with intravitreal anti-vascular endothelial growth factor
      agents did not seem to directly alter their natural course. CONCLUSION: The
      authors report solid-appearing retinal cysts as a new optical coherence
      tomography finding in four patients with diabetic macular edema. The exact
      composition of this isoreflective material is unknown. The authors hypothesize
      that fibrin or other inflammatory by-products fill these spaces.

PMID- 25391119
TI  - Paracentral cone dystrophy with tapetal-like sheen and mizuo phenomenon examined
      with different imaging techniques.
AB  - PURPOSE: To present a case report of a patient diagnosed with cone dystrophy,
      with an uncommon presentation of paracentral involvement, tapetallike sheen, and
      Mizuo phenomenon. METHODS: The patient underwent complete ophthalmic examination,
      repeated electroretinograms, fluorescein angiography, spectral-domain optical
      coherence tomography, autofluorescence, and different techniques for fundus
      photographs (color, infrared, red free). PATIENT: Twenty-year-old male patient
      who manifested slight photofobia but was otherwise asymptomatic. RESULTS: The
      patient had 20/20 vision in both eyes. Upon indirect ophthalmoscopy, the retina
      presented a metalliclike sheen. Sequential electroretinograms and multifocal
      electroretinogram demonstrated a decreasing photopic response, with paracentral
      involvement. Autofluorescence and spectral-domain optical coherence tomography
      allowed a better visualization of the atrophic parafoveal cones. Red-free
      photographs help document the tapetallike sheen and Mizuo phenomenon after 3-hour
      dark adaptation. CONCLUSION: The final diagnosis of cone dystrophy, paracentral,
      with tapetallike sheen was established. Spectral-domain optical coherence
      tomography and red-free photographs will help better understand the
      pathophysiology and clinical manifestations of this uncommon disease.

PMID- 25391120
TI  - Regression of takayasu retinopathy after revascularization of occluded branches
      of the aortic arch by percutaneous angioplasty.
AB  - PURPOSE: To present a patient with decreased vision because of Takayasu
      retinopathy who had improvement in vision and regression of retinopathy after
      percutaneous angioplasty of occluded aortic arch vessels. METHODS: Interventional
      case report. RESULTS: A 37-year-old woman with multiple cerebral infarcts and
      recurrent seizures was referred with painless progressive reduction in vision in
      the right eye of few months' duration and left eye for 2 years. Vision was 20/120
      in the right eye and perception of light in the left eye. There was mild disk
      pallor in the right eye, optic atrophy in the left eye, and microaneursyms in
      both eyes. Angiographic findings were consistent with type I Takayasu arteritis.
      Angioplasty and stenting was performed initially to the right subclavian and
      common carotid arteries and to the left subclavian, and left internal carotid
      arteries 6 weeks later. There was improvement in vision to 20/80 and regression
      of Takayasu retinopathy in the right eye at 3 months post procedure that improved
      further to 20/50, 6 months post procedure. Vision, as expected, remained poor in
      the left eye despite revascularization. CONCLUSION: Restoration of flow in the
      aortic arch vessels may result in reversal of ischemic retinal changes in
      patients with Takayasu retinopathy.

PMID- 25391121
TI  - Secondary orbital and intraocular lymphoma treated with immunochemotherapy.
AB  - PURPOSE: To assess ocular and orbital structure by ocular echography and magnetic
      resonance imaging, fluoroangiography, indocyanine green angiography, and optical
      coherence tomography before and after therapy with rituximab (Mabthera) and
      chlorambucil in a patient with concurrent intraorbital and intraocular lymphoma
      and diplopia. METHODS: A 69-year-old man referred blurred vision and proptosis in
      his left eye associated with diplopia. Best-corrected visual acuity was 0.3
      logarithm of the minimum angle of resolution in the left eye and 0.02 logarithm
      of the minimum angle of resolution in the right eye. Ocular echography and
      magnetic resonance imaging revealed the presence of concurrent orbital and
      intraocular tumor, and a B-cell lymphocytic lymphoma was diagnosed by incisional
      biopsy. The patient was treated with the oral alkylating agent chlorambucil and
      with intravenous infusions of the monoclonal anti-CD20 antibody rituximab
      (Mabthera) and evaluated with visual acuity, echography, fluoroangiography,
      indocyanine green angiography, and magnetic resonance imaging. RESULTS: After
      combined immunochemotherapy with rituximab/chlorambucil, the patient showed in
      the left eye a significant improvement of visual acuity (0.1 logarithm of the
      minimum angle of resolution) and a disappearance of diplopia at the end of follow
      up. CONCLUSION: In this case report, combined systemic therapy with chlorambucil
      and rituximab was effective to reduce and control orbital and intraocular
      lymphoma.

PMID- 25391122
TI  - Retinal microangiopathy as an initial manifestation of familial amyloid
      cardiomyopathy associated with transthyretin e89k mutation.
AB  - PURPOSE: To report a rare case of transthyretin (TTR) familial amyloid
      cardiomyopathy with retinal microangiopathy and vitreous amyloid as the initial
      manifestation. METHODS: A 54-year-old woman presented with bilateral retinal
      microangiopathy, presumed idiopathic retinal vasculitis. She subsequently
      developed retinal ischemia associated vitreous hemorrhage and was treated with
      panretinal laser photocoagulation. Clinical eye signs remained stable for 6 years
      with the absence of overt inflammation. However, the patient developed chest pain
      and atrial flutter and underwent echocardiography, cardiac magnetic resonance
      imaging, and Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy
      to investigate possible cardiac amyloidosis. Sequencing of the TTR gene was
      conducted and a rectal biopsy performed for tissue diagnosis. A full neurologic
      screen was also conducted. RESULTS: Cardiac investigations were highly suggestive
      of an amyloid cardiomyopathy. The rectal biopsy stained positive for Congo red
      with demonstration of apple green birefringence, confirming amyloid, and
      immunostaining confirmed the TTR subtype. Gene sequencing revealed heterozygous
      TTR mutation encoding E89K variant. No significant neuropathy could be detected.
      CONCLUSION: Amyloid should be considered as a masquerade diagnosis in cases of
      retinal microangiopathy, especially in the absence of inflammation. Liaising with
      physicians for systemic evaluation and TTR gene sequencing is essential for early
      diagnosis and management of this rare condition.

PMID- 25391123
TI  - Late spectral-domain optical coherence tomography findings in sub-internal
      limiting membrane hemorrhage.
AB  - PURPOSE: To report spectral-domain optical coherence tomographic (OCT) findings
      during the natural history of a sub-internal limiting membrane (sub-ILM)
      hemorrhage. METHODS: Observational case report of a 20-year-old man with myeloid
      acute leukemia who presented a spontaneous resolution of a premacular hemorrhage,
      which was demonstrated by OCT. During the 12-month follow-up, periodic
      ophthalmologic and OCT examinations were performed. RESULTS: A premacular
      hemorrhage was revealed in fundus examination, and spectral-domain OCT
      demonstrated a highly hyperreflective band just above the premacular hemorrhage
      consistent with the ILM. At 6-month follow-up, the macula was free of blood. The
      OCT scans after spontaneous resolution of the hemorrhage showed a thickened
      hyperreflective membrane (ILM) and a prominent hyporeflective premacular cavity.
      Six months later, this premacular cavity had resolved. CONCLUSION: These late OCT
      findings in sub-ILM hemorrhage have not been described in spontaneous evolution
      and confirm the sub-ILM location of a premacular hemorrhage.

PMID- 25391124
TI  - Flecked retina, choroidopathy, and retinal pigment epithelial tear in familial
      pulmonary arterial hypertension.
AB  - BACKGROUND: Thanks to advancement in treatment modalities, the medial survival
      rate of patients with familial pulmonary arterial hypertension (FPAH) has been
      improved. Unfortunately, ocular complications because of the chronically elevated
      systemic venous pressure become more frequent. METHODS: The authors report new
      FPAH-associated fundus changes in a 50-year-old male patient treated with
      sildenafil. The anomalies were studied with autofluorescence, fluorescein and
      indocyanine green angiography, and spectral optical coherence tomography
      including enhanced depth imaging. RESULTS: Loss of vision and cystoid macular
      edema were associated with a flecked retina, a thick choroid, central serous
      choroidopathy-like changes in both eyes and with retinal pigment epithelium
      detachments and a retinal pigment epithelium tear in the right eye. CONCLUSION:
      Treatment of ocular findings associated with FPAH mainly involves optimal control
      of pulmonary arterial hypertension and ophthalmic supportive treatment toward
      preventing acute ocular complications. The ocular complications occur as a result
      of enhanced pressure in the superior vena cava and in the ophthalmic veins,
      resulting in dilation of the ocular veins and congestion of the choroid.
      Sildenafil treatment in FPAH may enhance the congestion of the choroid and can
      induce central serous choroidopathy-like changes. A flecked retina, central
      serous choroidopathy-like changes, and retinal pigment epithelium tear are rare
      complications of FPAH.

PMID- 25391125
TI  - Enhanced depth imaging spectral domain optical coherence tomography in syphilitic
      chorioretinitis.
AB  - PURPOSE: To describe the enhanced depth imaging optical coherence tomography
      features in syphilitic chorioretinitis. METHODS: This is a case report. RESULTS:
      A 69-year-old man was diagnosed with syphilitic chorioretinitis after presenting
      with a 3-week history of blurred vision in his right eye. Fundus examination
      revealed vitritis and retinal whitening along the inferotemporal arcade. Enhanced
      depth imaging optical coherence tomography showed choroidal thickening and
      increased reflectivity of the overlying retina. Intravenous penicillin G was
      started and clinical improvement followed with corresponding reduction in
      choroidal thickness and decreased reflectivity of the overlying retina.
      CONCLUSION: Enhanced depth imaging optical coherence tomography can be used in
      conjunction with clinical examination to localize tissue involvement in
      syphilitic chorioretinitis and monitor treatment response.

PMID- 25391126
TI  - Headaches secondary to intraventricular silicone oil successfully managed with
      ventriculoperitoneal shunt.
AB  - PURPOSE: To describe a case of intravitreal silicone oil (SO) migration into the
      cerebral ventricles with secondary chronic headaches. METHODS: Retrospective case
      report. Chart review. Single patient. RESULTS: A 51-year-old man with a history
      of proliferative diabetic retinopathy underwent surgery for traction retinal
      detachment using SO. Postoperatively, he developed elevated intraocular pressure,
      headaches, and a blind painful eye, which was enucleated. Neuroimaging revealed
      SO within the cerebral ventricles. Five years after the initial retinal
      detachment surgery, the patient developed chronic headaches. Lumbar puncture
      revealed an elevated opening pressure. The headaches were initially managed
      medically. A ventriculoperitoneal shunt was placed after the headaches persisted,
      which resulted in their complete resolution at 6 weeks after shunt placement.
      CONCLUSION: Ocular hypertension after intravitreal SO placement may play a role
      in SO intracranial migration. In the case presented, intraventricular SO was the
      apparent cause of elevated intracranial pressure and headaches. As all published
      cases of intraventricular SO migration reporting intraocular pressure to this
      point have described ocular hypertension, careful monitoring of intraocular
      pressure and aggressive control of ocular hypertension in the presence of
      intravitreal SO is recommended.

PMID- 25391127
TI  - Conjunctival pyogenic granuloma associated with intravitreal bevacizumab
      injection.
AB  - PURPOSE: To report a case of conjunctival pyogenic granuloma after intravitreal
      injection of anti-vascular endothelial growth factor, bevacizumab. METHODS: A 52
      year-old patient after 3 intravitreal bevacizumab injections was found to have a
      vascular conjunctival nodule at the injection site. A pathologic analysis of the
      vascular conjunctival nodule was performed after surgical excision. RESULTS: The
      pathologic analysis revealed a conjunctival pyogenic granuloma. CONCLUSION:
      Conjunctival pyogenic granuloma can complicate an otherwise uneventful
      intravitreal anti-vascular endothelial growth factor injection.

PMID- 25391128
TI  - Circumscribed outer foveolar defects in spinocerebellar ataxia type 7.
AB  - PURPOSE: To report circumscribed outer foveolar defects in a 40-year-old man with
      a history of spinocerebellar ataxia type 7. METHODS: A 40-year-old man with
      genetically confirmed spinocerebellar ataxia type 7 presented with progressive
      vision loss and decreased color perception for 3 years. He underwent a full
      ocular examination, fundus photography, autofluorescence, spectral-domain optical
      coherence tomography imaging, and a full-field electroretinogram. RESULTS: The
      patient's ocular examination and fundus autofluorescence were both normal except
      for mild temporal pallor of both optic discs. Spectral-domain optical coherence
      tomographic imaging showed foveal thinning with an outer foveolar defect because
      of focal loss of photoreceptors, disruption of the inner segment-outer segment
      junction but preservation of the external limiting membrane, and thinning of the
      outer plexiform layer in both eyes. Electroretinography showed severely reduced
      cone function with mildly reduced rod function. CONCLUSION: Spinocerebellar
      ataxia type 7 should be included in the differential diagnosis for "outer retinal
      holes" or "foveal cavitation," which also includes solar retinopathy, juxtafoveal
      telangiectasia, Welder maculopathy, tamoxifen retinopathy, Stargardt disease,
      amyl nitrate abuse, and cone or cone-rod degeneration syndromes.

PMID- 25391129
TI  - Adverse reactions to plain gut, polyglycolic Acid, and polyglactin 910 sutures
      for sclerotomy closure at pars plana vitrectomy.
AB  - PURPOSE: To evaluate the rates of adverse reactions to suture materials and
      compare the rates for plain gut, polyglycolic acid, and polyglactin 910. METHODS:
      Postoperative adverse suture reaction rates were compared using Fisher exact
      test. One hundred and forty-six patients who underwent pars plana vitrectomy were
      included in this study. RESULTS: Adverse suture reaction rates were 2% (1/48) for
      plain gut, 30% (6/20) for polyglycolic acid, and 12% (11/78) for polyglactin 910.
      CONCLUSION: Plain gut suture was associated with fewer adverse suture reactions
      when compared with polyglycolic acid and polyglactin 910 and seems to be suitable
      for sclerotomy closure.

PMID- 25391130
TI  - Holy smoke in medieval funerary rites: chemical fingerprints of frankincense in
      southern Belgian incense burners.
AB  - Frankincense, the oleogum resin from Boswellia sp., has been an early luxury good
      in both Western and Eastern societies and is particularly used in Christian
      funerary and liturgical rites. The scant grave goods in late medieval burials
      comprise laterally perforated pottery vessels which are usually filled with
      charcoal. They occur in most regions of western Europe and are interpreted as
      incense burners but have never been investigated with advanced analytical
      techniques. We herein present chemical and anthracological results on perforated
      funerary pots from 4 Wallonian sites dating to the 12-14th century AD.
      Chromatographic and mass spectrometric analysis of lipid extracts of the ancient
      residues and comparison with extracts from four Boswellia species clearly
      evidence the presence of degraded frankincense in the former, based on
      characteristic triterpenoids, viz. boswellic and tirucallic acids, and their
      myriad dehydrated and oxygenated derivatives. Cembrane-type diterpenoids indicate
      B. sacra (southern Arabia) and B. serrata (India) as possible botanical origins.
      Furthermore, traces of juniper and possibly pine tar demonstrate that small
      amounts of locally available fragrances were mixed with frankincense, most likely
      to reduce its cost. Additionally, markers of ruminant fats in one sample from a
      domestic context indicate that this vessel was used for food preparation.
      Anthracological analysis demonstrates that the charcoal was used as fuel only and
      that no fragrant wood species were burned. The chars derived from local woody
      plants and were most likely recovered from domestic fires. Furthermore, vessel
      recycling is indicated by both contextual and biomarker evidence. The results
      shed a new light on funerary practices in the Middle Ages and at the same time
      reveal useful insights into the chemistry of burned frankincense. The discovery
      of novel biomarkers, namely Delta2-boswellic acids and a series of
      polyunsaturated and aromatic hydrocarbons, demonstrates the high potential for
      organic chemical analyses of incense residues. 

PMID- 25391131
TI  - Two metallothionein genes in Oxya chinensis: molecular characteristics,
      expression patterns and roles in heavy metal stress.
AB  - Metallothioneins (MTs) are small, cysteine-rich, heavy metal-binding proteins
      involved in metal homeostasis and detoxification in living organisms. In the
      present study, we cloned two MT genes (OcMT1 and OcMT2) from Oxya chinensis,
      analyzed the expression patterns of the OcMT transcripts in different tissues and
      at varying developmental stages using real-time quantitative PCR (RT-qPCR),
      evaluated the functions of these two MTs using RNAi and recombinant proteins in
      an E. coli expression system. The full-length cDNAs of OcMT1 and OcMT2 encoded 40
      and 64 amino acid residues, respectively. We found Cys-Cys, Cys-X-Cys and Cys-X-Y
      Z-Cys motifs in OcMT1 and OcMT2. These motifs might serve as primary chelating
      sites, as in other organisms. These characteristics suggest that OcMT1 and OcMT2
      may be involved in heavy metal detoxification by capturing the metals. Two OcMT
      were expressed at all developmental stages, and the highest levels were found in
      the eggs. Both transcripts were expressed in all eleven tissues examined, with
      the highest levels observed in the brain and optic lobes, followed by the fat
      body. The expression of OcMT2 was also relatively high in the ovaries. The
      functions of OcMT1 and OcMT2 were explored using RNA interference (RNAi) and
      different concentrations and treatment times for the three heavy metals. Our
      results indicated that mortality increased significantly from 8.5% to 16.7%, and
      this increase was both time- and dose-dependent. To evaluate the abilities of
      these two MT proteins to confer heavy metal tolerance to E. coli, the bacterial
      cells were transformed with pET-28a plasmids containing the OcMT genes. The
      optical densities of both the MT-expressing and control cells decreased with
      increasing concentrations of CdCl2. Nevertheless, the survival rates of the MT
      overexpressing cells were higher than those of the controls. Our results suggest
      that these two genes play important roles in heavy metal detoxification in O.
      chinensis. 

PMID- 25391132
TI  - The importance of bank vole density and rainy winters in predicting nephropathia
      epidemica incidence in Northern Sweden.
AB  - Pathogenic hantaviruses (family Bunyaviridae, genus Hantavirus) are rodent-borne
      viruses causing hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In
      Europe, there are more than 10,000 yearly cases of nephropathia epidemica (NE), a
      mild form of HFRS caused by Puumala virus (PUUV). The common and widely
      distributed bank vole (Myodes glareolus) is the host of PUUV. In this study, we
      aim to explain and predict NE incidence in boreal Sweden using bank vole
      densities. We tested whether the number of rainy days in winter contributed to
      variation in NE incidence. We forecast NE incidence in July 2013-June 2014 using
      projected autumn vole density, and then considering two climatic scenarios: 1)
      rain-free winter and 2) winter with many rainy days. Autumn vole density was a
      strong explanatory variable of NE incidence in boreal Sweden in 1990-2012 (R2 =
      79%, p<0.001). Adding the number of rainy winter days improved the model (R2 =
      84%, p<0.05). We report for the first time that risk of NE is higher in winters
      with many rainy days. Rain on snow and ground icing may block vole access to
      subnivean space. Seeking refuge from adverse conditions and shelter from
      predators, voles may infest buildings, increasing infection risk. In a rainy
      winter scenario, we predicted 812 NE cases in boreal Sweden, triple the number of
      cases predicted in a rain-free winter in 2013/2014. Our model enables
      identification of high risk years when preparedness in the public health sector
      is crucial, as a rainy winter would accentuate risk. 

PMID- 25391133
TI  - Decitabine rescues cisplatin resistance in head and neck squamous cell carcinoma.
AB  - Cisplatin resistance in head and neck squamous cell carcinoma (HNSCC) reduces
      survival. In this study we hypothesized that methylation of key genes mediates
      cisplatin resistance. We determined whether a demethylating drug, decitabine,
      could augment the anti-proliferative and apoptotic effects of cisplatin on SCC
      25/CP, a cisplatin-resistant tongue SCC cell line. We showed that decitabine
      treatment restored cisplatin sensitivity in SCC-25/CP and significantly reduced
      the cisplatin dose required to induce apoptosis. We then created a xenograft
      model with SCC-25/CP and determined that decitabine and cisplatin combination
      treatment resulted in significantly reduced tumor growth and mechanical allodynia
      compared to control. To establish a gene classifier we quantified methylation in
      cancer tissue of cisplatin-sensitive and cisplatin-resistant HNSCC patients.
      Cisplatin-sensitive and cisplatin-resistant patient tumors had distinct
      methylation profiles. When we quantified methylation and expression of genes in
      the classifier in HNSCC cells in vitro, we showed that decitabine treatment of
      cisplatin-resistant HNSCC cells reversed methylation and gene expression toward a
      cisplatin-sensitive profile. The study provides direct evidence that decitabine
      restores cisplatin sensitivity in in vitro and in vivo models of HNSCC.
      Combination treatment of cisplatin and decitabine significantly reduces HNSCC
      growth and HNSCC pain. Furthermore, gene methylation could be used as a biomarker
      of cisplatin-resistance. 

PMID- 25391134
TI  - Soil charcoal to assess the impacts of past human disturbances on tropical
      forests.
AB  - The canopy of many central African forests is dominated by light-demanding tree
      species that do not regenerate well under themselves. The prevalence of these
      species might result from ancient slash-and-burn agricultural activities that
      created large openings, while a decline of these activities since the colonial
      period could explain their deficit of regeneration. To verify this hypothesis, we
      compared soil charcoal abundance, used as a proxy for past slash-and-burn
      agriculture, and tree species composition assessed on 208 rainforest 0.2 ha plots
      located in three areas from Southern Cameroon. Species were classified in
      regeneration guilds (pioneer, non-pioneer light-demanding, shade-bearer) and
      characterized by their wood-specific gravity, assumed to reflect light
      requirement. We tested the correlation between soil charcoal abundance and: (i)
      the relative abundance of each guild, (ii) each species and family abundance and
      (iii) mean wood-specific gravity. Charcoal was found in 83% of the plots,
      indicating frequent past forest fires. Radiocarbon dating revealed two periods of
      fires: "recent" charcoal were on average 300 years old (up to 860 BP, n = 16) and
      occurred in the uppermost 20 cm soil layer, while "ancient" charcoal were on
      average 1900 years old (range: 1500 to 2800 BP, n = 43, excluding one sample
      dated 9400 BP), and found in all soil layers. While we expected a positive
      correlation between the relative abundance of light-demanding species and
      charcoal abundance in the upper soil layer, overall there was no evidence that
      the current heterogeneity in tree species composition can be explained by
      charcoal abundance in any soil layer. The absence of signal supporting our
      hypothesis might result from (i) a relatively uniform impact of past slash-and
      burn activities, (ii) pedoturbation processes bringing ancient charcoal to the
      upper soil layer, blurring the signal of centuries-old Human disturbances, or
      (iii) the prevalence of other environmental factors on species composition. 

PMID- 25391135
TI  - The impact of antiretroviral therapy on mortality in HIV positive people during
      tuberculosis treatment: a systematic review and meta-analysis.
AB  - OBJECTIVE: To quantify the impact of antiretroviral therapy (ART) on mortality in
      HIV-positive people during tuberculosis (TB) treatment. DESIGN: We conducted a
      systematic literature review and meta-analysis. Studies published from 1996
      through February 15, 2013, were identified by searching electronic resources
      (Pubmed and Embase) and conference books, manual searches of references, and
      expert consultation. Pooled estimates for the outcome of interest were acquired
      using random effects meta-analysis. SUBJECTS: The study population included
      individuals receiving ART before or during TB treatment. MAIN OUTCOME MEASURES:
      Main outcome measures were: (i) TB-case fatality ratio (CFR), defined as the
      proportion of individuals dying during TB treatment and, if mortality in HIV
      positive people not on ART was also reported, (ii) the relative risk of death
      during TB treatment by ART status. RESULTS: Twenty-one studies were included in
      the systematic review. Random effects pooled meta-analysis estimated the CFR
      between 8% and 14% (pooled estimate 11%). Among HIV-positive TB cases, those
      receiving ART had a reduction in mortality during TB treatment of between 44% and
      71% (RR = 0.42, 95%CI: 0.29-0.56). CONCLUSION: Starting ART before or during TB
      therapy reduces the risk of death during TB treatment by around three-fifths in
      clinical settings. National programmes should continue to expand coverage of ART
      for HIV positive in order to control the dual epidemic.

PMID- 25391136
TI  - Analysis of non-typeable Haemophilous influenzae VapC1 mutations reveals
      structural features required for toxicity and flexibility in the active site.
AB  - Bacteria have evolved mechanisms that allow them to survive in the face of a
      variety of stresses including nutrient deprivation, antibiotic challenge and
      engulfment by predator cells. A switch to dormancy represents one strategy that
      reduces energy utilization and can render cells resistant to compounds that kill
      growing bacteria. These persister cells pose a problem during treatment of
      infections with antibiotics, and dormancy mechanisms may contribute to latent
      infections. Many bacteria encode toxin-antitoxin (TA) gene pairs that play an
      important role in dormancy and the formation of persisters. VapBC gene pairs
      comprise the largest of the Type II TA systems in bacteria and they produce a
      VapC ribonuclease toxin whose activity is inhibited by the VapB antitoxin.
      Despite the importance of VapBC TA pairs in dormancy and persister formation,
      little information exists on the structural features of VapC proteins required
      for their toxic function in vivo. Studies reported here identified 17 single
      mutations that disrupt the function of VapC1 from non-typeable H. influenzae in
      vivo. 3-D modeling suggests that side chains affected by many of these mutations
      sit near the active site of the toxin protein. Phylogenetic comparisons and
      secondary mutagenesis indicate that VapC1 toxicity requires an alternative active
      site motif found in many proteobacteria. Expression of the antitoxin VapB1
      counteracts the activity of VapC1 mutants partially defective for toxicity,
      indicating that the antitoxin binds these mutant proteins in vivo. These findings
      identify critical chemical features required for the biological function of VapC
      toxins and PIN-domain proteins. 

PMID- 25391137
TI  - Patterns of spatial and temporal distribution of humpback whales at the southern
      limit of the Southeast Pacific breeding area.
AB  - Understanding the patterns of spatial and temporal distribution in threshold
      habitats of highly migratory and endangered species is important for
      understanding their habitat requirements and recovery trends. Herein, we present
      new data about the distribution of humpback whales (Megaptera novaeangliae) in
      neritic waters off the northern coast of Peru: an area that constitutes a
      transitional path from cold, upwelling waters to warm equatorial waters where the
      breeding habitat is located. Data was collected during four consecutive austral
      winter/spring seasons from 2010 to 2013, using whale-watching boats as platforms
      for research. A total of 1048 whales distributed between 487 groups were sighted.
      The spatial distribution of humpbacks resembled the characteristic segregation of
      whale groups according to their size/age class and social context in breeding
      habitats; mother and calf pairs were present in very shallow waters close to the
      coast, while dyads, trios or more whales were widely distributed from shallow to
      moderate depths over the continental shelf break. Sea surface temperatures
      (range: 18.2-25.9 degrees C) in coastal waters were slightly colder than those
      closer to the oceanic realm, likely due to the influence of cold upwelled waters
      from the Humboldt Current system. Our results provide new evidence of the
      southward extension of the breeding region of humpback whales in the Southeast
      Pacific. Integrating this information with the knowledge from the rest of the
      breeding region and foraging grounds would enhance our current understanding of
      population dynamics and recovery trends of this species. 

PMID- 25391138
TI  - Alginate inhibits iron absorption from ferrous gluconate in a randomized
      controlled trial and reduces iron uptake into Caco-2 cells.
AB  - Previous in vitro results indicated that alginate beads might be a useful vehicle
      for food iron fortification. A human study was undertaken to test the hypothesis
      that alginate enhances iron absorption. A randomised, single blinded, cross-over
      trial was carried out in which iron absorption was measured from serum iron
      appearance after a test meal. Overnight-fasted volunteers (n = 15) were given a
      test meal of 200 g cola-flavoured jelly plus 21 mg iron as ferrous gluconate,
      either in alginate beads mixed into the jelly or in a capsule. Iron absorption
      was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6%
      respectively, p = 0.003). Sub-group B (n = 9) consumed the test meals together
      with 600 mg calcium to determine whether alginate modified the inhibitory effect
      of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from
      11.5% to 5.6% (p = 0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p =
      0.009). In vitro studies using Caco-2 cells were designed to explore the reasons
      for the difference between the previous in vitro findings and the human study;
      confirmed the inhibitory effect of alginate. Beads similar to those used in the
      human study were subjected to simulated gastrointestinal digestion, with and
      without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and
      cola jelly significantly reduced iron uptake into the cells, by 34% (p = 0.009)
      and 35% (p = 0.003) respectively. The combination of cola jelly and calcium
      produced a very low ferritin response, 16.5% (p < 0.001) of that observed with
      ferrous gluconate alone. The results of these studies demonstrate that alginate
      beads are not a useful delivery system for soluble salts of iron for the purpose
      of food fortification. TRIAL REGISTRATION: ClinicalTrials.gov NCT01528644.

PMID- 25391139
TI  - Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage
      Disease type V).
AB  - Background McArdle disease (Glycogen Storage Disease type V) is caused by an
      absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria
      rhabdomyolysis and acute renal failure. This is an update of a review first
      published in 2004.Objectives To review systematically the evidence from
      randomised controlled trials (RCTs) of pharmacological or nutritional treatments
      for improving exercise performance and quality of life in McArdle disease.Search
      methods We searched the Cochrane Neuromuscular Disease Group Specialized
      Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We
      included RCTs (including cross-over studies) and quasi-RCTs. We included
      unblinded open trials and individual patient studies in the discussion.
      Interventions included any pharmacological agent or nutritional supplement.
      Primary outcome measures included any objective assessment of exercise endurance
      (for example aerobic capacity (VO2) max, walking speed, muscle force or power and
      fatigability). Secondary outcome measures included metabolic changes (such as
      reduced plasma creatine kinase and a reduction in the frequency of
      myoglobinuria), subjective measures (including quality of life scores and indices
      of disability) and serious adverse events.Data collection and analysis Three
      review authors checked the titles and abstracts identified by the search and
      reviewed the manuscripts. Two review authors independently assessed the risk of
      bias of relevant studies, with comments from a third author. Two authors
      extracted data onto a specially designed form.Main results We identified 31
      studies, and 13 fulfilled the criteria for inclusion. We described trials that
      were not eligible for the review in the Discussion. The included studies involved
      a total of 85 participants, but the number in each individual trial was small;
      the largest treatment trial included 19 participants and the smallest study
      included only one participant. There was no benefit with: D-ribose,glucagon,
      verapamil, vitamin B6, branched chain amino acids, dantrolene sodium, and high
      dose creatine. Minimal subjective benefit was found with low dose creatine and
      ramipril only for patients with a polymorphism known as the D/Dangiotens in
      converting enzyme(ACE) phenotype. A carbohydrate-rich diet resulted in better
      exercise performance compared with a protein-rich diet. Two studies of oral
      sucrose given at different times and in different amounts before exercise showed
      an improvement in exercise performance. Four studies reported adverse effects.
      Oral ribose caused diarrhoea and symptoms suggestive of hypoglycaemia including
      light-headedness and hunger. In one study, branched chain amino acids caused a
      deterioration of functional outcomes. Dantrolene was reported to cause a number
      of adverse effects including tiredness, somnolence, dizziness and muscle
      weakness. Low dose creatine (60 mg/kg/day) did not cause side-effects but high
      dose creatine (150 mg/kg/day) worsened the symptoms of myalgia.Authors'
      conclusions Although there was low quality evidence of improvement in some
      parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet,
      none was sufficiently strong to indicate significant clinical benefit.

PMID- 25391140
TI  - House dust mite induced lung inflammation does not alter circulating vitamin D
      levels.
AB  - Low circulating levels of 25-hydroxyvitamin D [25(OH)D] are associated with
      chronic lung diseases such as asthma. However, it is unclear whether vitamin D is
      involved in disease pathogenesis or is modified by the inflammation associated
      with the disease process. We hypothesized that allergic inflammation decreases
      the level of circulating 25(OH)D and tested this using a mice model of house dust
      mite (HDM) induced allergic airway inflammation. Cellular influx was measured in
      bronchoalvelar lavage (BAL) fluid, and allergic sensitization and 25(OH)D levels
      were measured in serum. Exposure to HDM caused a robust inflammatory response in
      the lung that was enhanced by prior influenza infection. These responses were not
      associated with any change in circulating levels of 25(OH)D. These data suggest
      that alterations in circulating 25(OH)D levels induced by Th-2 driven
      inflammation are unlikely to explain the cross-sectional epidemiological
      association between vitamin D deficiency and asthma. 

PMID- 25391141
TI  - Morphological and physiological responses of cotton (Gossypium hirsutum L.)
      plants to salinity.
AB  - Salinization usually plays a primary role in soil degradation, which consequently
      reduces agricultural productivity. In this study, the effects of salinity on
      growth parameters, ion, chlorophyll, and proline content, photosynthesis,
      antioxidant enzyme activities, and lipid peroxidation of two cotton cultivars,
      [CCRI-79 (salt tolerant) and Simian 3 (salt sensitive)], were evaluated. Salinity
      was investigated at 0 mM, 80 mM, 160 mM, and 240 mM NaCl for 7 days. Salinity
      induced morphological and physiological changes, including a reduction in the dry
      weight of leaves and roots, root length, root volume, average root diameter,
      chlorophyll and proline contents, net photosynthesis and stomatal conductance. In
      addition, salinity caused ion imbalance in plants as shown by higher Na+ and Cl-
      contents and lower K+, Ca2+, and Mg2+ concentrations. Ion imbalance was more
      pronounced in CCRI-79 than in Simian3. In the leaves and roots of the salt
      tolerant cultivar CCRI-79, increasing levels of salinity increased the activities
      of superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione
      reductase (GR), but reduced catalase (CAT) activity. The activities of SOD, CAT,
      APX, and GR in the leaves and roots of CCRI-79 were higher than those in Simian
      3. CAT and APX showed the greatest H2O2 scavenging activity in both leaves and
      roots. Moreover, CAT and APX activities in conjunction with SOD seem to play an
      essential protective role in the scavenging process. These results indicate that
      CCRI-79 has a more effective protection mechanism and mitigated oxidative stress
      and lipid peroxidation by maintaining higher antioxidant activities than those in
      Simian 3. Overall, the chlorophyll a, chlorophyll b, and Chl (a+b) contents, net
      photosynthetic rate and stomatal conductance, SOD, CAT, APX, and GR activities
      showed the most significant variation between the two cotton cultivars. 

PMID- 25391142
TI  - The vocal repertoire of adult and neonate giant otters (Pteronura brasiliensis).
AB  - Animals use vocalizations to exchange information about external events, their
      own physical or motivational state, or about individuality and social
      affiliation. Infant babbling can enhance the development of the full adult vocal
      repertoire by providing ample opportunity for practice. Giant otters are very
      social and frequently vocalizing animals. They live in highly cohesive groups,
      generally including a reproductive pair and their offspring born in different
      years. This basic social structure may vary in the degree of relatedness of the
      group members. Individuals engage in shared group activities and different social
      roles and thus, the social organization of giant otters provides a basis for
      complex and long-term individual relationships. We recorded and analysed the
      vocalizations of adult and neonate giant otters from wild and captive groups. We
      classified the adult vocalizations according to their acoustic structure, and
      described their main behavioural context. Additionally, we present the first
      description of vocalizations uttered in babbling bouts of new born giant otters.
      We expected to find 1) a sophisticated vocal repertoire that would reflect the
      species' complex social organisation, 2) that giant otter vocalizations have a
      clear relationship between signal structure and function, and 3) that the vocal
      repertoire of new born giant otters would comprise age-specific vocalizations as
      well as precursors of the adult repertoire. We found a vocal repertoire with 22
      distinct vocalization types produced by adults and 11 vocalization types within
      the babbling bouts of the neonates. A comparison within the otter subfamily
      suggests a relation between vocal and social complexity, with the giant otters
      being the socially and vocally most complex species. 

PMID- 25391143
TI  - The effect of online violent video games on levels of aggression.
AB  - BACKGROUND: In recent years the video game industry has surpassed both the music
      and video industries in sales. Currently violent video games are among the most
      popular video games played by consumers, most specifically First-Person Shooters
      (FPS). Technological advancements in game play experience including the ability
      to play online has accounted for this increase in popularity. Previous research,
      utilising the General Aggression Model (GAM), has identified that violent video
      games increase levels of aggression. Little is known, however, as to the effect
      of playing a violent video game online. METHODS/PRINCIPAL FINDINGS: Participants
      (N = 101) were randomly assigned to one of four experimental conditions; neutral
      video game--offline, neutral video game--online, violent video game--offline and
      violent video game--online. Following this they completed questionnaires to
      assess their attitudes towards the game and engaged in a chilli sauce paradigm to
      measure behavioural aggression. The results identified that participants who
      played a violent video game exhibited more aggression than those who played a
      neutral video game. Furthermore, this main effect was not particularly pronounced
      when the game was played online. CONCLUSIONS/SIGNIFICANCE: These findings suggest
      that both playing violent video games online and offline compared to playing
      neutral video games increases aggression.

PMID- 25391144
TI  - Pigeon navigation: different routes lead to Frankfurt.
AB  - BACKGROUND: Tracks of pigeons homing to the Frankfurt loft revealed an odd
      phenomenon: whereas birds returning from the North approach their loft more or
      less directly in a broad front, pigeons returning from the South choose, from 25
      km from home onward, either of two corridors, a direct one and one with a
      considerable detour to the West. This implies differences in the navigational
      process. METHODOLOGY/PRINCIPLE FINDINGS: Pigeons released at sites at the
      beginning of the westerly corridor and in this corridor behave just like pigeons
      returning from farther south, deviating to the west before turning towards their
      loft. Birds released at sites within the straight corridors, in contrast, take
      more or less straight routes. The analysis of the short-term correlation
      dimension, a quantity reflecting the complexity of the system and with it, the
      number of factors involved in the navigational process, reveals that it is
      significantly larger in pigeons choosing the westerly corridor than in the birds
      flying straight - 3.03 vs. 2.85. The difference is small, however, suggesting a
      different interpretation of the same factors, with some birds apparently
      preferring particular factors over others. CONCLUSIONS: The specific regional
      distribution of the factors which pigeons use to determine their home course
      seems to provide ambiguous information in the area 25 km south of the loft,
      resulting in the two corridors. Pigeons appear to navigate by deriving their
      routes directly from the locally available navigational factors which they
      interpret in an individual way. The fractal nature of the correlation dimensions
      indicates that the navigation process of pigeons is chaotic-deterministic;
      published tracks of migratory birds suggest that this may apply to avian
      navigation in general.

PMID- 25391145
TI  - The actin targeting compound Chondramide inhibits breast cancer metastasis via
      reduction of cellular contractility.
AB  - BACKGROUND: A major player in the process of metastasis is the actin cytoskeleton
      as it forms key structures in both invasion mechanisms, mesenchymal and amoeboid
      migration. We tested the actin binding compound Chondramide as potential anti
      metastatic agent. METHODS: In vivo, the effect of Chondramide on metastasis was
      tested employing a 4T1-Luc BALB/c mouse model. In vitro, Chondramide was tested
      using the highly invasive cancer cell line MDA-MB-231 in Boyden-chamber assays,
      fluorescent stainings, Western blot and Pull down assays. Finally, the
      contractility of MDA-MB-231 cells was monitored in 3D environment and analyzed
      via PIV analysis. RESULTS: In vivo, Chondramide treatment inhibits metastasis to
      the lung and the migration and invasion of MDA-MB-231 cells is reduced by
      Chondramide in vitro. On the signaling level, RhoA activity is decreased by
      Chondramide accompanied by reduced MLC-2 and the stretch induced guanine
      nucleotide exchange factor Vav2 activation. At same conditions, EGF-receptor
      autophosphorylation, Akt and Erk as well as Rac1 are not affected. Finally,
      Chondramide treatment disrupted the actin cytoskeleton and decreased the ability
      of cells for contraction. CONCLUSIONS: Chondramide inhibits cellular
      contractility and thus represents a potential inhibitor of tumor cell invasion.

PMID- 25391147
TI  - MHD mixed convective peristaltic motion of nanofluid with Joule heating and
      thermophoresis effects.
AB  - The primary objective of present investigation is to introduce the novel aspect
      of thermophoresis in the mixed convective peristaltic transport of viscous
      nanofluid. Viscous dissipation and Joule heating are also taken into account.
      Problem is modeled using the lubrication approach. Resulting system of equations
      is solved numerically. Effects of sundry parameters on the velocity, temperature,
      concentration of nanoparticles and heat and mass transfer rates at the wall are
      studied through graphs. It is noted that the concentration of nanoparticles near
      the boundaries is enhanced for larger thermophoresis parameter. However reverse
      situation is observed for an increase in the value of Brownian motion parameter.
      Further, the mass transfer rate at the wall significantly decreases when Brownian
      motion parameter is assigned higher values. 

PMID- 25391146
TI  - Glimepiride promotes osteogenic differentiation in rat osteoblasts via the
      PI3K/Akt/eNOS pathway in a high glucose microenvironment.
AB  - Our previous studies demonstrated that glimepiride enhanced the proliferation and
      differentiation of osteoblasts and led to activation of the PI3K/Akt pathway.
      Recent genetic evidence shows that endothelial nitric oxide synthase (eNOS) plays
      an important role in bone homeostasis. In this study, we further elucidated the
      roles of eNOS, PI3K and Akt in bone formation by osteoblasts induced by
      glimepiride in a high glucose microenvironment. We demonstrated that high glucose
      (16.5 mM) inhibits the osteogenic differentiation potential and proliferation of
      rat osteoblasts. Glimepiride activated eNOS expression in rat osteoblasts
      cultured with two different concentrations of glucose. High glucose-induced
      osteogenic differentiation was significantly enhanced by glimepiride. Down
      regulation of PI3K P85 levels by treatment with LY294002 (a PI3K inhibitor) led
      to suppression of P-eNOS and P-AKT expression levels, which in turn resulted in
      inhibition of RUNX2, OCN and ALP mRNA expression in osteoblasts induced by
      glimepiride at both glucose concentrations. ALP activity was partially inhibited
      by 10 uM LY294002. Taken together, our results demonstrate that glimepiride
      induced osteogenic differentiation of osteoblasts occurs via eNOS activation and
      is dependent on the PI3K/Akt signaling pathway in a high glucose
      microenvironment. 

PMID- 25391148
TI  - Worldwide niche and future potential distribution of Culicoides imicola, a major
      vector of bluetongue and African horse sickness viruses.
AB  - We modelled the ecoclimatic niche of Culicoides imicola, a major arthropod vector
      of midge-borne viral pathogens affecting ruminants and equids, at fine scale and
      on a global extent, so as to provide insight into current and future risks of
      disease epizootics, and increase current knowledge of the species' ecology. Based
      on the known distribution and ecology of C. imicola, the species' response to
      monthly climatic conditions was characterised using CLIMEX with 10' spatial
      resolution climatic datasets. The species' climatic niche was projected worldwide
      and under future climatic scenarios. The validated model highlights the role of
      irrigation in supporting the occurrence of C. imicola in arid regions. In Europe,
      the modelled potential distribution of C. imicola extended further West than its
      reported distribution, raising questions regarding ongoing process of
      colonization and non-climatic habitat factors. The CLIMEX model highlighted
      similar ecological niches for C. imicola and the Australasian C. brevitarsis
      raising questions on biogeography and biosecurity. Under the climate change
      scenarios considered, its' modelled potential distribution could expand northward
      in the Northern hemisphere, whereas in Africa its range may contract in the
      future. The biosecurity risks from bluetongue and African horse sickness viruses
      need to be re-evaluated in regions where the vector's niche is suitable. Under a
      warmer climate, the risk of vector-borne epizootic pathogens such as bluetongue
      and African horse sickness viruses are likely to increase as the climate
      suitability for C. imicola shifts poleward, especially in Western Europe. 

PMID- 25391149
TI  - Neem leaf glycoprotein prophylaxis transduces immune dependent stop signal for
      tumor angiogenic switch within tumor microenvironment.
AB  - We have reported that prophylactic as well as therapeutic administration of neem
      leaf glycoprotein (NLGP) induces significant restriction of solid tumor growth in
      mice. Here, we investigate whether the effect of such pretreatment (25ug/mice;
      weekly, 4 times) benefits regulation of tumor angiogenesis, an obligate factor
      for tumor progression. We show that NLGP pretreatment results in vascular
      normalization in melanoma and carcinoma bearing mice along with downregulation of
      CD31, VEGF and VEGFR2. NLGP pretreatment facilitates profound infiltration of
      CD8+ T cells within tumor parenchyma, which subsequently regulates VEGF-VEGFR2
      signaling in CD31+ vascular endothelial cells to prevent aberrant
      neovascularization. Pericyte stabilization, VEGF dependent inhibition of VEC
      proliferation and subsequent vascular normalization are also experienced. Studies
      in immune compromised mice confirmed that these vascular and intratumoral changes
      in angiogenic profile are dependent upon active adoptive immunity particularly
      those mediated by CD8+ T cells. Accumulated evidences suggest that NLGP regulated
      immunomodulation is active in tumor growth restriction and normalization of tumor
      angiogenesis as well, thereby, signifying its clinical translation. 

PMID- 25391151
TI  - A recommended numbering scheme for influenza A HA subtypes.
AB  - Comparisons of residues between sub-types of influenza virus is increasingly used
      to assess the zoonotic potential of a circulating strain and for comparative
      studies across subtypes. An analysis of N-terminal cleavage sites for thirteen
      subtypes of influenza A hemagglutinin (HA) sequences, has previously been
      described by Nobusawa and colleagues. We have expanded this analysis for the
      eighteen known subtypes of influenza. Due to differences in the length of HA, we
      have included strains from multiple clades of H1 and H5, as well as strains of H5
      and H7 subtypes with both high and low pathogenicity. Analysis of known
      structures of influenza A HA enables us to define amino acids which are
      structurally and functionally equivalent across all HA subtypes using a numbering
      system based on the mature HA sequence. We provide a list of equivalences for
      amino acids which are known to affect the phenotype of the virus. 

PMID- 25391152
TI  - Alkaloids modulate motility, biofilm formation and antibiotic susceptibility of
      uropathogenic Escherichia coli.
AB  - Alkaloid-containing natural compounds have shown promise in the treatment of
      microbial infections. However, practical application of many of these compounds
      is pending a mechanistic understanding of their mode of action. We investigated
      the effect of two alkaloids, piperine (found in black pepper) and reserpine
      (found in Indian snakeroot), on the ability of the uropathogenic bacterium
      Escherichia coli CFT073 to colonize abiotic surfaces. Sub-inhibitory
      concentrations of both compounds (0.5 to 10 ug/mL) decreased bacterial swarming
      and swimming motilities and increased biofilm formation. qRT-PCR revealed a
      decrease in the expression of the flagellar gene (fliC) and motility genes (motA
      and motB) along with an increased expression of adhesin genes (fimA, papA, uvrY).
      Interestingly, piperine increased penetration of the antibiotics ciprofloxacin
      and azithromycin into E. coli CFT073 biofilms and consequently enhanced the
      ability of these antibiotics to disperse pre-established biofilms. The findings
      suggest that these alkaloids can potentially affect bacterial colonization by
      hampering bacterial motility and may aid in the treatment of infection by
      increasing antibiotic penetration in biofilms. 

PMID- 25391153
TI  - An odorant-binding protein is abundantly expressed in the nose and in the seminal
      fluid of the rabbit.
AB  - We have purified an abundant lipocalin from the seminal fluid of the rabbit,
      which shows significant similarity with the sub-class of pheromone carriers
      "urinary" and "salivary" and presents an N-terminal sequence identical with that
      of an odorant-binding protein (rabOBP3) expressed in the nasal tissue of the same
      species. This protein is synthesised in the prostate and found in the seminal
      fluid, but not in sperm cells. The same protein is also expressed in the nasal
      epithelium of both sexes, but is completely absent in female reproductive organs.
      It presents four cysteines, among which two are arranged to form a disulphide
      bridge, and is glycosylated. This is the first report of an OBP identified at the
      protein level in the seminal fluid of a vertebrate species. The protein purified
      from seminal fluid is bound to some organic chemicals whose structure is
      currently under investigation. We reasonably speculate that, like urinary and
      salivary proteins reported in other species of mammals, this lipocalin performs a
      dual role, as carrier of semiochemicals in the seminal fluid and as detector of
      chemical signals in the nose. 

PMID- 25391154
TI  - Migratory birds reinforce local circulation of avian influenza viruses.
AB  - Migratory and resident hosts have been hypothesized to fulfil distinct roles in
      infectious disease dynamics. However, the contribution of resident and migratory
      hosts to wildlife infectious disease epidemiology, including that of low
      pathogenic avian influenza virus (LPAIV) in wild birds, has largely remained
      unstudied. During an autumn H3 LPAIV epizootic in free-living mallards (Anas
      platyrhynchos) - a partially migratory species - we identified resident and
      migratory host populations using stable hydrogen isotope analysis of flight
      feathers. We investigated the role of migratory and resident hosts separately in
      the introduction and maintenance of H3 LPAIV during the epizootic. To test this
      we analysed (i) H3 virus kinship, (ii) temporal patterns in H3 virus prevalence
      and shedding and (iii) H3-specific antibody prevalence in relation to host
      migratory strategy. We demonstrate that the H3 LPAIV strain causing the epizootic
      most likely originated from a single introduction, followed by local clonal
      expansion. The H3 LPAIV strain was genetically unrelated to H3 LPAIV detected
      both before and after the epizootic at the study site. During the LPAIV
      epizootic, migratory mallards were more often infected with H3 LPAIV than
      residents. Low titres of H3-specific antibodies were detected in only a few
      residents and migrants. Our results suggest that in this LPAIV epizootic, a
      single H3 virus was present in resident mallards prior to arrival of migratory
      mallards followed by a period of virus amplification, importantly associated with
      the influx of migratory mallards. Thus migrants are suggested to act as local
      amplifiers rather than the often suggested role as vectors importing novel
      strains from afar. Our study exemplifies that a multifaceted interdisciplinary
      approach offers promising opportunities to elucidate the role of migratory and
      resident hosts in infectious disease dynamics in wildlife. 

PMID- 25391155
TI  - Modafinil increases the latency of response in the Hayling Sentence Completion
      Test in healthy volunteers: a randomised controlled trial.
AB  - BACKGROUND: Modafinil is a medication licensed for the treatment of narcolepsy.
      However, it has been reported that healthy individuals without wakefulness
      disorders are using modafinil off-label to enhance cognitive functioning.
      Although some studies have reported that modafinil improves cognitive task
      performance in healthy volunteers, numerous other studies have failed to detect
      cognitive enhancing effects of modafinil on several well-established
      neuropsychological tasks. Interestingly, several clinical and preclinical studies
      have found that improved cognitive task performance by modafinil is accompanied
      by slower response times. This observation raises the question as to whether this
      slowing of response time in healthy volunteers is a necessary and sufficient
      condition for cognitive enhancement with modafinil. The aim of the current
      experiment was to explore this question by investigating the effects of modafinil
      on the Hayling Sentence Completion Test (HSCT). METHODOLOGY: Sixty-four healthy
      volunteers received either a single dose (200 mg) of modafinil (n = 32) or
      placebo (n = 32) in a randomized, double-blind, placebo-controlled, parallel
      group study in which the principal outcome measures were response latencies on
      the response initiation and response inhibition sections of the HSCT. PRINCIPAL
      FINDINGS: Participants dosed with modafinil had significantly longer mean
      response latencies on the HSCT for both the response initiation and response
      inhibition compared to participants dosed with placebo. However, participants in
      both groups made a similar number of errors on each of these measures, indicating
      that modafinil did not enhance the accuracy of performance of the task relative
      to placebo. CONCLUSIONS: This study demonstrated that administration of single
      200 mg doses of modafinil to healthy individuals increased the latency of
      responses in the performance of the HSCT, a task that is highly sensitive to
      prefrontal executive function, without enhancing accuracy of performance. This
      finding may provide important clues to defining the limitations of modafinil as a
      putative cognitive enhancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02051153.

PMID- 25391157
TI  - Prevention.  New vaccine focuses on mucosal membrane.

PMID- 25391156
TI  - Serum inflammatory cytokine levels correlate with hand-foot-mouth disease
      severity: a nested serial case-control study.
AB  - BACKGROUND: Hand-food-mouth disease (HFMD) cases can be fatal. These cases
      develop rapidly, and it is important to predict the severity of HFMD from mild to
      fatal and to identify risk factors for mild HFMD. The objective of this study was
      to correlate the levels of serum inflammatory cytokines with HFMD severity.
      METHODS: This study was designed as a nested serial case-control study. The data
      collected included general information, clinical symptoms and signs, laboratory
      findings and serum cytokine levels. RESULTS: The levels of IL-4, IL-6, IL-10, TNF
      alpha and IFN-gamma in patients with severe HFMD were significantly higher than
      in mild patients during the 2nd to 5th day after disease onset. The levels of IL
      4, IL-6, IL-10 and IFN-gamma increased from the 2nd day to the 4th day and later
      decreased. The levels of TNF-alpha were high on the first two days and
      subsequently decreased. The changes of IL-10, TNF-alpha and IFN-gamma in the
      controls were similar for all cases. The levels of IL-4, IL-6 and IL-17 in the
      controls were not significantly different with the progression of HFMD.
      CONCLUSIONS: Our findings indicate that the IL-4, IL-6, IL-10, TNF-alpha and IFN
      gamma levels correlate with HFMD severity.

PMID- 25391158
TI  - Disparities in treatment retention persist among young, black MSM.

PMID- 25391159
TI  - Prevention.  Social networking strategy helps identify people with HIV.

PMID- 25391160
TI  - UCSF to run helpline for physicians prescribing PrEP.

PMID- 25391161
TI  - Stimulant use doesn't diminish benefits of ART.

PMID- 25391162
TI  - Prisons.  HIV med policy did not violate inmates' constitutional rights.

PMID- 25391163
TI  - Endoscopic endonasal surgery for olfactory groove meningiomas: outcomes and
      limitations in 50 patients.
AB  - OBJECT: Recently, endoscopic endonasal surgery (EES) has been introduced in the
      management of skull base tumors, with constantly improving outcomes and
      increasing indications. The authors retrospectively reviewed the effectiveness of
      EES in the management of olfactory groove meningiomas. METHODS: Between February
      2003 and December 2012, 50 patients (64% female) with olfactory groove
      meningiomas underwent EES at the University of Pittsburgh Medical Center. The
      authors present the results of EES and analyze the resection rates, clinical
      outcome, complications, and limitations of this approach. RESULTS: Forty-four
      patients presented with primary tumors, whereas six were previously treated
      elsewhere. The patients' mean age was 57.1 years (range 27-88 years). Clinical
      presentation included altered mental status (36%), visual loss (30%), headache
      (24%), and seizures (20%). The mean maximum tumor diameter was 41.6 mm (range 18
      80 mm). All patients underwent EES, which was performed in stages in 18 giant
      tumors. Complete tumor resection (Simpson Grade I) was achieved in 66.7% of the
      45 patients in whom it was the goal, and 13 (28.9%) had neartotal resection (>
      95% of the tumor). Tumor size, calcification, and absence of cortical cuff from
      vasculature were significant factors that influenced the degree of resection (p =
      0.002, p = 0.024, and p = 0.028, respectively). Tumor residual was usually at the
      most lateral and anterior tumor margins. Following EES, mental status was
      improved or normalized in 77.8% of the cases, vision was improved or restored in
      86.7%, and headaches resolved in 83.3%. There was no postoperative deterioration
      of presenting symptoms. Complications were increased in tumors > 40 mm and
      included CSF leakage (30%), which was significantly associated with lobular tumor
      configuration (p = 0.048); pulmonary embolism/deep vein thrombosis, more commonly
      in elderly patients (20%); sinus infections (10%); and delayed abscess months or
      years after EES (6%). One patient had an intraoperative vascular injury resulting
      in transient hemiparesis (2%). There were no perioperative deaths. During a mean
      follow-up period of 32 months (median 22 months, range 1-115 months), 1 patient
      underwent repeat EES for tumor regrowth. CONCLUSIONS: Endoscopic endonasal
      surgery has shown good clinical outcomes regardless of patient age, previous
      treatment, or tumor characteristics. Tumor size > 40 mm, calcification, and
      absence of cortical vascular cuff limit GTR with EES; in addition, large tumors
      are associated with increased postoperative complications. Significant lateral
      and anterior dural involvement may represent indications for using traditional
      craniotomies for the management of these tumors. Postoperative CSF leakage
      remains a problem that necessitates innovations in EES reconstruction techniques.

PMID- 25391164
TI  - Should endoscopic endonasal surgery be used in the treatment of olfactory groove
      meningiomas?

PMID- 25391165
TI  - Outcome of acute lymphoblastic leukemia treatment using national protocols at the
      Queen Sirikit National Institute of Child Health.
AB  - OBJECTIVE: To evaluate the outcome of acute lymphoblastic leukemia (ALL)
      treatment at the Queen Sirikit National Institute of Child Health (QSNICH) after
      using national protocols. MATERIAL AND METHOD: Seventy-six pediatric patients
      with newly diagnosed with ALL, who were treated in Queen Sirikit National
      Institute of Child Health using the national protocols during March 2006 and
      February 2008, were enrolled. The national protocols were sub-classified by
      clinical risk factors and morphology of leukemic cells of the patients at initial
      presentation into 3 groups as standard risk (ALL-01-05), high-risk (ALL-02-05),
      and mature B-ALL or L3 (NHL-04-06) protocol. Overall survival (OS) and event-free
      survival (EFS) were determined by using Kaplan-Meier survival curves. RESULTS:
      The overall survival rate of ALL patients treated using the national protocols
      was 83.85% (88.06% in standard group, 82.01% in high-risk group, and 75% in L3
      protocol). The mortality rate and event-free survival of ALL patients was 13.33%
      and 72.50%, respectively. CONCLUSION: The national protocols for ALL showed
      benefit in the improvement of outcomes from treatment in childhood ALL.

PMID- 25391166
TI  - Concurrent validity of the Ages & Stages Questionnaires, Third Edition, Thai
      version (ASQ-3 Thai) with the Denver Developmental Screening Test II (DDST-II) in
      developmental screening of 18, 24, and 30 months old children at Queen Sirikit
      National Institute of Child Health.
AB  - OBJECTIVE: To determine the concurrent validity of the Ages & Stages
      Questionnaires, Third Edition, Thai-version (ASQ-3 Thai) with the Denver
      Developmental Screening Test II (DDST-II) and agreement between them in
      developmental status screening in toddlers. MATERIAL AND METHOD: Children at the
      ages of 18, 24, and 30 months were enrolled. Each age group included 15 normal
      and 15 suspected cases. Participants were developmentally assessed by the DDST-II
      performed by a developmental pediatrician (BS). Parents of the enrolled children
      simultaneously completed their toddler's age-specific version of the ASQ-3 Thai
      questionnaire. Concurrent validity of the ASQ-3 Thai with DDST-II was determined
      by descriptive statistics using the cross tabulation technique. Kappa analysis
      was used to calculate agreement between the ASQ-3 Thai and DDST-II. RESULTS: A
      fair to moderate agreement (Kappa agreement = 0.338-0.606) was found between the
      ASQ-3 Thai and the DDST-II. Sensitivity of the ASQ-3 Thai with DDST-II at the age
      of 18, 24, and 30 months were 66.7%, 88.2%, and 54.5%, respectively. Specificity
      of the tool when compared to the DDST-II were 78.6%, 71.4% and 90.9%,
      respectively. CONCLUSION: This was a preliminary study of the ASQ-3 Thai version
      for developmental screening in clinical setting. Due to a fair to moderate
      agreement but low sensitivity between the ASQ-3 Thai and DDST-II, other validated
      tools should accompany the clinical usage of the tool. Further investigations are
      needed to support its usage, particularly the validation of the tool with other
      standardized developmental diagnostic tools.

PMID- 25391167
TI  - SLC39A4 mutation in zinc deficiency patients.
AB  - OBJECTIVE: To analyze the clinical presentation and SLC39A4 mutations in zinc
      deficiency patients. MATERIAL AND METHOD: The authors conducted a cross-sectional
      study on all cases of zinc deficiency treated at Queen Sirikit National Institute
      of Child Health between January 2004 and December 2012. Demographic data,
      clinical manifestations, laboratory results, treatment and outcome were analyzed.
      Genetic, SLC39A4 for acrodermatitis enteropathic (AE), mutation analysis was
      performed in all cases. RESULTS: There were 15 cases, 10 males and 5 females. The
      age of onset was between 2 and 10 months (median 3 months). Duration of the
      disease ranged between 3 days and 17 months (median 2 months). Acral and
      periorificial dermatitis, diarrhea and alopecia were present in 15 cases (100%),
      12 cases (80%) and 8 cases (53%) respectively. The characteristic triad of acral
      and periorificial dermatitis, diarrhea and alopecia was observed in only 6
      patients (40%). Serum zinc level ranged between 10 and 111 mcg/dl (mean 49.69 +/-
      33.87 mcg/100 ml). Low serum zinc level was observed in 10 cases (67%). All of
      the patients were treated with zinc sulfate 5 mg/kg/day. All cutaneous lesions
      and diarrhea had resolved within 7 days of starting therapy. A genetic study of
      SLC39A4 gene in our 15 patients revealed that 3 patients had homozygous
      c.1878_1879ins21 (p.G627_T633dup) in exonl2. These three patients have to receive
      lifelong zinc supplementation to prevent recurrence of the disease. The other
      twelve patients, who did not carry the gene mutation, did not have symptoms after
      discontinuance of oral zinc therapy. This is the first report of genetically
      confirmed acrodermatitis enteropathic in Thailand. CONCLUSION: Acrodermatitis
      enteropathica is a rare disease, which needs lifelong zinc supplementation. A
      genetic study of SLC39A4 gene will confirm the diagnosis. Most of patients
      presenting with characteristic triad of acral and periorificial dermatitis,
      diarrhea and alopecia in Thailand were acquired zinc deficiency. Early
      recognition and treatment of the disease will decrease morbidity and mortality.

PMID- 25391168
TI  - Effect of oral probiotics supplementation in the prevention of necrotizing
      enterocolitis among very low birth weight preterm infants.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is the most serious gastrointestinal
      problem in very low birth weight preterm infants. Multiple risk factors activate
      the inflammatory cascade leading to high expressions of pro-inflammatory
      mediators causing bowel injury in NEC. The anti-inflammatory effect of probiotics
      is due to the inhibition and reduction of inflammatory signal in intestinal
      epithelium. OBJECTIVE: To evaluate the efficacy of probiotics supplementation in
      the prevention of NEC among very low birth weight preterm infants. STUDY DESIGN:
      A prospective randomized controlled trial. MATERIAL AND METHOD: All preterm
      infants with gestational age less than or equal to 34 weeks and birth weight less
      than or equal to 1,500 grams admitted in neonatal care unit, Queen Sirikit
      National Institute of Child Health during June 1st, 2012 and January 31th, 2013
      were enrolled in this study. They were randomized into two groups, study and
      control group. Infants in the study group were fed Infloran (Lactobacillus
      acidophilus 1 x 10(9) and Bifidobacterium bifidum 1 x 10(9) organisms) dose 125
      mg/kg/dose twice a day with breast milk or premature formula from the start of
      feeding until 6 weeks or discharge. Infants in the control group were fed with
      either breast milk or premature formula alone. The primary outcome was NEC stage
      >= 2. RESULTS: Sixty infants completed the study, 31 infants in the study group
      and 29 infants in the control group. The baseline characteristic data of infants
      were similar except for more males in the present study group. Incidence of NEC
      stage >= 2 were similar in both the groups, 3.2 vs. 3.4% (p = 0.74). There were
      no deaths during the study period. Days to reach full feeding, 150 ml/kg/day,
      were no differences between the two groups, 12.03 +/- 5.49 days vs. 13.76 +/-
      8.25 days (p = 0.31). No adverse effects such as sepsis, flatulence or diarrhea
      were noted. CONCLUSION: In this study, there was no difference in incidence of
      NEC stage >= 2 between the two groups. No adverse effects of probiotics
      supplementation were observed.

PMID- 25391169
TI  - The incidence and risk factors of apnea in premature infants underwent general
      anesthesia for cryotherapy or laser photocoagulation for treatment of retinopathy
      of prematurity at Queen Sirikit National Institute of Child Health.
AB  - OBJECTIVE: To determine the incidence and risk factors of postoperative apnea in
      premature infants who received general anesthesia for cryotherapy or laser
      photocoagulation for treatment of retinopathy of prematurity (ROP) at Queen
      Sirikit National Institute of Child Health. MATERIAL AND METHOD: A retrospective
      cohort study was performed by reviewing medical records of premature infants with
      ROP who underwent general anesthesia for cryotherapy or laser photocoagulation
      during January 2008 and December 2010 at Queen Sirikit National Institute of
      Child Health. The incidence and risk factors of postoperative apnea were
      analyzed. RESULTS: Forty of 167 (24%) premature infants had apnea after general
      anesthesia for treatment of ROP. The risk factors were post-conceptual age and
      history of apnea. The risk of apnea in patients with post-conceptual age less
      than 35 weeks was 5.7 times higher than in patients with post-conceptual age more
      than 37 weeks (95% CI 1.59-20.45). Patients with a prior history of apnea had a
      6.42 times greater risk of postoperative apnea compared to patients without a
      prior history of apnea (95% CI 2.01-20.50). No other serious complications were
      reported during the study period. CONCLUSION: The incidence of apnea after
      general anesthesia in infants with ROP treated with cryotherapy or laser
      photocoagulation was 24%. The risk factors of postoperative apnea were post
      conceptual age less than 35 weeks and prior history of apnea. Patients with risk
      factors should be closely monitored.

PMID- 25391170
TI  - Comparative growth outcome of preterm neonate fed post-discharge formula and
      breast milk after discharge.
AB  - OBJECTIVE: To evaluate the post-discharge growth, laboratory outcome,
      neurodevelopment and safety of post-discharge formula in comparison to breast
      milk. MATERIAL AND METHOD: A prospective cohort of preterm infants, who were
      discharged on breast milk or post-discharge formula (PDF) were studied.
      Demographic data, post-discharge growth, laboratory outcome, neurodevelopment and
      complications were recorded. These infants were followed-up at 40 weeks'
      postmenstrual age (PMA) 2, 4 and 6 months' corrected age. The present study was
      conducted for 22 months (from September 1, 2011-May 31, 2013). RESULTS: Seventeen
      infants were enrolled in the study, 7 in the breastfed group and 10 in the PDF
      group. Mean maternal age in breastfed group were significantly younger compared
      with PDF-fed group. PDF-fed infants were longer with statistical significantly at
      40 weeks PMA and 4 months' corrected age (p < 0.05). At 2 months' corrected age,
      babies in breast milk group were significantly heavier compared to those in PDF
      group. Conversely, those in PDF group were heavier than the breastfed group at 4
      months' corrected age (p < 0.05). There was no difference of head circumference
      between groups at follow-up. A higher serum phosphorus and lower serum alkaline
      phosphatase were related to improve suspected osteopenia of prematurity at 2
      months' corrected age in PDF group (p = 0.007). Hematocrit was higher in the PDF
      group than breastfed group, which was statistically significant at 40 weeks'
      postmenstrual age and 6 months' corrected age. There were no significant
      diferences in developmental screening in both groups. CONCLUSION: Post-discharge
      formula may improve growth, hematocrit and reduce suspected osteopenia of
      prematurity. However neurodevelopment outcome and complications were similar to
      both groups.

PMID- 25391171
TI  - Risk factors and outcomes of influenza infection among children presenting with
      influenza-like illness.
AB  - OBJECTIVE: Limited data were available to guide management, counseling, and/or
      diagnostic investigation among children presenting with influenza-like illness
      (ILI). During a recent period of high influenza activity, we wished to determine
      the frequency, outcomes, and factors associated with influenza infection among
      children presenting with ILI. MATERIAL AND METHOD: During September and October
      2010, children presenting with ILI were enrolled. Nasal swabs were sent for
      polymerase chain reaction (PCR) to determine the frequency and types of
      influenza. Information of demographic characteristics, potential risk factors,
      and short-term outcomes of study participants were collected. RESULTS: Among 300
      enrolled subjects, influenza infections were identified in 170 (56.7%) cases;
      45.7% (n = 137) were influenza A and 11% (n = 33) were influenza B. Most cases
      recovered uneventfully with a 3.7% (n = 11) hospitalization rate. Risks for
      hospitalization did not differ by infection status (2.4% vs. 5.4% between those
      with and without influenza infection, respectively) or types of influenza
      infection. Logistic regression analysis indicated that older age, having a
      household member with acute respiratory illness (ARI) during the previous 7 days,
      having an underlying co-morbidity, and a history of premature birth were
      associated with influenza, with adjusted odds ratios and 95% confidence intervals
      of 1.19 (1.087, 1.30), 3.21 (1.096, 9.424), 2.15 (1.244, 3.728), and 0.08 (0.007,
      0.876), respectively. CONCLUSION: The outcomes of influenza-associated ILI were
      generally favourable, with no fatalities and 2.4% risk for hospitalization. Among
      children presenting with ILI, age, household contact with ARI, and co morbidities
      increased the likelihood of influenza, whereas history of premature birth was
      negatively associated with influenza.

PMID- 25391172
TI  - Quality of life and happiness of the students in the disaster area: 6 years after
      the Tsunami at Takua Pa District, Phang Nga, Thailand.
AB  - BACKGROUND: The Tsunami disaster, which occurred on December 26, 2004 in
      Thailand, caused enormous damage to life, property and community. Although the
      tragedy occurred 6 years ago, many children and adolescents still suffer from
      mental health problems. OBJECTIVE: To determine the quality of life and happiness
      of students who live in the Tsunami disaster area 6 years after the tragedy.
      MATERIAL AND METHOD: A cross-sectional study was done on 648 students from three
      schools in Takua Pa district, Phang Nga. They had been provided with
      psychological or support by multidisciplinary teams from Queen Sirikit National
      Institute of Child Health, Siriraj Hospital and Chulalongkorn Hospital. The
      questionnaires consisted of 3 subsets which were self-report of general
      information, pediatric quality of life inventory and Thai happiness indicator.
      RESULTS: The student's quality of life was low 15.1%, moderate 68.7% and high
      16.2%. Eighteen percent had good (27-42) score higher, 38% had a fair (27-32)
      score and 44% had a poor (< 27) score. Females and high school performance were
      associated with happiness. CONCLUSION: Disasters have long lasting effects on
      victims, especially in children. Although this group of children had regularly
      received assistance including welfare, finance, education and health advice, most
      had fair quality of life scores were fair and poor-is this needed. Nearly half of
      them had happiness level scores less than average. They still have psychosocial
      problems and will need long-term monitoring, support and assistance.

PMID- 25391173
TI  - Vitamin supplementation and related nutritional status in Thai children, aged 1-5
      years.
AB  - OBJECTIVE: To evaluate the prevalence of vitamin supplementation in Thai children
      aged 1-5 years at Queen Sirikit National Institute of Child Health (QSNICH),
      parental knowledge of vitamins, practices, and related factors such as
      nutritional status in vitamin supplementation. MATERIAL AND METHOD: A cross
      sectional study was performed at the Well Child Clinic, QSNICH, from 1-31 May
      2005. Five hundred parents of young children, aged 1-5 years were interviewed by
      using the questionnaire to obtain information regarding knowledge and practices
      of vitamin supplementation. Weight and length/height were measured and
      nutritional status was assessed using the Thai growth reference. The
      relationships among vitamin supplement, nutritional status, and other related
      factors were analyzed using Chi-square test. The p-value < 0.05 was considered
      statistically significant. RESULTS: Prevalence of vitamin supplementation was
      76%, including vitamin C 62%, multi-vitamin (MTV) 35%, and cod-liver oil 20%.
      Regarding parental knowledge of vitamins, 57% of them knew the health benefits
      but 74% did not know the toxic effects of vitamins. The reasons for vitamin
      supplementation were poor feeding 63%, under-weight 23% and unhealthy status 14%.
      Vitamins were obtained from over-the-counter 59%, health services 40%, and
      friends 1%. Vitamin supplementation was significantly higher in children over 2
      years of age, whose parents knew the benefits of vitamins, and in those children
      with malnutrition. CONCLUSION: The prevalence of vitamin supplementation was high
      in malnourished children, over 2 years of age whose parents had knowledge about
      benefits of vitamins. Parents should be warned about the dangers of high dose of
      vitamin consumption.

PMID- 25391174
TI  - Association of adolescent substance use: behavioral problems and family
      background among school students in Tsunami affected area in southern Thailand.
AB  - OBJECTIVE: To study the prevalence of substance use and associated factors in
      school students in Tsunami affected areas in southern Thailand. MATERIAL AND
      METHOD: The study was a school-based, cross-sectional, anonymous survey that used
      a translated questionnaire, ESPAD-03, in 5 schools. Chi-square tests and odds
      ratios were used to evaluate factors associated with substance use. RESULTS: Two
      thousand seven hundred and sixteen students (87.8%) were enrolled in the study.
      Lifetime, last 12 months, and last 30 days prevalence rates of any substance use
      were 50.3, 33.9, and 24.8%, respectively. Lifetime, last 12 months, and last 30
      days prevalence rates of alcohol use were 43.2, 30.1, and 17.5%, respectively.
      Lifetime and last 30 days prevalence rates of smoking were 21.7 and 12.0%.
      Fighting, stealing, truancy, running away, unsafe sex, and thought of self
      harming were associated with alcohol and substance use. Siblings and friends with
      alcohol and substance use were risk factors. Close support from parents and
      friends were protective factors. CONCLUSION: There was a high prevalence of
      smoking, alcohol, and substance use among school students in Tsunami affected
      areas. Behavioral problems and psychosocial risk factors were associated with
      history of smoking, alcohol and substance use. School-based intervention in
      students with behavioral problems seems to be a worthwhile investment. However,
      longitudinal studies should be done to confirm the correlation of PTSD and
      substance use.

PMID- 25391175
TI  - How to manage low gut obstruction in neonates with immature ganglion cells in the
      colonic wall?
AB  - BACKGROUND: Neonates with immature ganglion cells in the colonic wall may have
      the clinical picture similar to Hirschsprung's disease, especially total colonic
      aganglionosis. Management of this entity depends on the judgment of each
      clinician. OBJECTIVE: The aim of this study was to review management of clinical
      low gut obstruction in neonates with presence of immature ganglion cells in the
      colon. MATERIAL AND METHOD: A retrospective study of neonates with clinical low
      gut obstruction due to presence of immature ganglion cells treated between 2007
      and 2012 was reviewed. RESULTS: Six patients, one term and 5 pre-term neonates,
      were proven to have immature ganglion cells in the colonic wall. They presented
      with delay or failure to pass meconium, progressive abdominal distension and
      bilious vomiting after birth. Abdominal films showed generalized small bowel
      dilatation and barium enemas revealed a microcolon in 4 of them. They underwent
      laparotomy between 4 and 11 days of life. A microcolon with a transitional zone
      (Tz) was seen at the terminal ileum, 30-75 cm proximal to the ileocecal valve.
      Colonic biopsy and the appendix revealed presence of immature ganglion cells and
      ileal biopsy at the Tz showed presence of normal ganglion cells. An ileostomy was
      performed at the Tz in all of the 5 premature neonates, while an enterostomy was
      not done in term infant. Closure of the enterostomy in the 5 premature cases was
      performed after they had been proven to have mature ganglion cells in the colonic
      wall by a rectal biopsy after the age of 3 months. All of the 6 cases were doing
      well on the last follow-up between 1 and 3 years. CONCLUSION: Functional low gut
      obstruction in neonates caused by immaturity of the colonic ganglion cells should
      be managed by laparotomy including biopsies of the colon, appendix and terminal
      ileum with enterostomy at the Tz. Closure of the enterostomy is done after
      presence of mature ganglion cells proven by a rectal biopsy after 3 months of
      age. Full-term neonates with immature ganglion cells in the colonic wall may be
      successfully managed conservatively without enterostomy.

PMID- 25391176
TI  - Neonatal lupus erythematosus: a 20-year retrospective study.
AB  - OBJECTIVE: To study clinical manifestations, investigations, treatment and
      outcomes of neonatal lupus erythematosus (NLE) patients and their mothers.
      MATERIAL AND METHOD: A retrospective descriptive study was performed to review
      the neonatal lupus erythematosus patients and their mothers at Queen Sirikit
      National Institute of Child Health during January 1993 to December 2013. The
      diagnostic criteria required the presence of clinical symptoms plus positive anti
      Ro/SSA or anti-La/SSB or both. RESULTS: There were 34 cases, 12 males and 22
      females. Age of onset of clinical manifestations was from birth to 60 days with
      median age of 21 days. Cutaneous, hepatobiliary, hematological and cardiac
      abnormalities were found in 88.2%, 61.2%, 50%, 14.7%, respectively. Cutaneous
      lesions included erythematous rash (70%), annular lesions (75.8%), petechiae
      (26.6%), raccoon eyes (26.6%), and telangiectasia (20%). Among those with hepatic
      involvement (n = 18), transaminitis was the most common finding (100%) followed
      by hepatosplenomegaly (38.8%) and cholestasis (22.2%). Seventeen cases (50%) had
      hematological problems including anemia (29.4%) and anemia with thrombocytopenia
      (20.6%). The most severe complication, complete heart block was found in 14.7% (n
      = 5). Anti-Ro/SSA and anti-La/SSB were positive in 91.1% and 58.8% of cases,
      respectively. All four babies with complete heart block were treated with
      pacemaker. Systemic corticosteroids were given to eleven babies due to severe
      skin lesions and hepatic involvement. There was no mortality during the study.
      Most neonatal lupus erythematosus mothers (24 cases, 74.2%) were asymptomatic.
      Ten mothers (25.8%) were diagnosed as autoimmune diseases (systemic lupus
      erythematosus in 6 cases and other autoimmune diseases in 4 cases). However, 7 of
      24 asymptomatic mothers developed SLE within 3 years after delivery. CONCLUSION:
      NLE should be suspected among neonates or young infants presenting with
      congenital heart block or skin rash with multi-system involvement despite a lack
      of concurrent maternal autoimmune diseases. Anti-Ro/SSA and/or anti-La/SSB are
      the most useful laboratory diagnosis. Most NLE patients without congenital heart
      block have relatively good prognosis.

PMID- 25391177
TI  - Central venous catheterization related complications in Pediatric Intensive Care
      Unit at Queen Sirikit National Institute of Child Health.
AB  - BACKGROUND: Central venous catheterization (CVC) is an indispensable route of
      venous access in management of critically ill patients. Potential CVC related
      complications include mechanical and infectious complications. OBJECTIVE: To
      determine type, incidence and risk factor of CVC related complications in
      pediatric patients. MATERIAL AND METHOD: Prospective observational study of all
      patients who underwent CVC in pediatric intensive care unit (PICU) at Queen
      Sirikit National Institute of Child Health, over a 1-year period. RESULTS: The
      study included 137 patients, of whom 63.5% were males. The mean age was 36.7 +/-
      4.4 months. There were 204 CVC attempts with total indwell time of 2,002 days.
      The rate of mechanical complication was 19%, including failure to place catheter
      (9.3%), hematoma (4.9%), arterial puncture (2%) and pneumothorax (1.5%). Patient
      body mass index (BMI) > 30 kg/m2, internal jugular venous catheterization, and
      longer insertion time (> 30 minutes) were associated with high mechanical
      complication rates. The incidence density of catheter related blood stream
      infection (CRBSI) was 7.5/1,000 catheter-days. Femoral vein placement had
      significant higher incidence of CRBSI. CONCLUSION: CVC related complications are
      comparable to previous studies. Risk factors of mechanical complications include
      high BMI, internal jugular venous catheterization and longer insertion time.
      Femoral venous catheterization is the only risk factor for CRBSI.

PMID- 25391178
TI  - Iloprost inhalation for the treatment of severe persistent pulmonary hypertension
      of the newborn, experience at QSNICH.
AB  - BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is the most
      serious condition that causes high mortality in term and post term infants. The
      authors have an experience of using high frequency oscillatory ventilation (HFOV)
      and inhaled nitric oxide (iNO) for treatment of this condition with a good
      result. However, due to high cost of iNo, other pulmonary vasodilators have been
      use. Sildenafil had some side effects of systemic hypotension. Thus, inhaled
      iloprost was introduced for treatment of PPHN at our institute. OBJECTIVE: To
      evaluate the outcome of inhaled iloprost for the treatment of PPHN. MATERIAL AND
      METHOD: This was a retrospective study. The data from medical records of
      newborns, diagnosed as persistent pulmonary hypertension of the newborn and had
      received inhaled iloprost from October 1st, 2008-October 31st, 2012, were
      reviewed. RESULTS: Nineteen cases of PPHN treated with inhaled iloprost were
      reviewed. Male to female ratio was 1.3 7:1 (11:8). Mean birth weight and
      gestational age of these patients were 2,997 +/- 531.63 grams and 37.9 +/- 2.51
      weeks, respectively. Meconium aspiration syndrome was the leading underlying
      cause of this condition. The mortality rate in this study was 21% (4 from 19
      cases). After the addition of inhaled iloprost, the oxygen index (OI) in the
      survivor group decreased significantly at one hour after treatment (from 32.89 to
      22.06, 18.76, 13. 76 at 1, 6, 12 hours, respectively). Oxygen saturation (SpO2)
      continued increasing after treatment in the survivor group (from 82.40% to
      92.20%, 95.00%, 95.80% at 1, 6, 12 hours, respectively) with significant
      difference at one hour. There was a significant difference of OI and SpO2 between
      the survivor and non-survivor groups after treatment. Low Apgar score at 5
      minutes and early diagnosis of PPHN were found statistically significant
      different in the non-survivor compared to the survivor groups. CONCLUSION:
      Inhaled iloprost could be used as an alternative treatment of PPHN without side
      effects of systemic hypotension.

PMID- 25391179
TI  - Persistent diarrhea: 15 years experience at a tertiary care hospital.
AB  - OBJECTIVE: To determine the risk factors, causative enteric pathogens, final
      diagnosis and treatment outcomes of persistent diarrhea in children. MATERIAL AND
      METHOD: A retrospective study of the patients who had diarrheal symptoms for at
      least 14 days diagnosed as persistent diarrhea (PD) and admitted at QSNICH during
      January 1997 and December 2011. Demographic data, risk factors, causative enteric
      pathogens, management and outcome were reviewed. RESULTS: The review included 79
      PD patients. Excluded were patients who were HIV seropositive, had GI anomalies
      and/or other underlying immune deficiencies. The demographic data showed mean age
      11.42 months and male:female 56:23 (2.43:1). Feeding with infant formula before
      admission was 43% compared to exclusive breastfeeding that was only 10%. Normal
      nutritional status was found in half of the cases (52.1%) and protein energy
      malnutrition (PEM) was present in 42.3%. Stool for enteropathogens was positive
      only in 49.4% and the most common being mixed enteropathogens. Secondary lactase
      deficiency was the cause of PD in half (50%) of the patients. Management
      consisted of rehydration, intravenous antibiotics 53%, and other adjuvant
      therapies such as cholestyramine, zinc and probiotics. Along with rehydration,
      all patients received aggressive nutritional management upon admission. The
      diarrhea subsided in less than 7 days in about 70% of the patients. CONCLUSION:
      The present study supports that important risk factors for PD are very young age
      group (especially under 1 year old), lack of breastfeeding and malnutrition.
      Enteropathogens were found in only about half of the patients and the most common
      cause of PD was secondary lactase deficiency. Most of the diarrhea subsided in
      less than 7 days of admission with proper management and aggressive nutrition
      upon admission.

PMID- 25391180
TI  - Demographics, clinical features, outcome and prognostic factors of Guillain-Barre
      syndrome in Thai children.
AB  - OBJECTIVE: To describe demographics, clinical profiles, management, outcomes and
      to determine factors associated with severity in Guillain-Barre Syndrome (GBS).
      MATERIAL AND METHOD: Medical records of GBS patients in Queen Sirikit National
      Institute of Child Health during 2000-2009 were searched. The data included
      demographics, clinical features, management and outcomes after 6 months to
      determine prognostic factors. RESULTS: Forty-eight patients with GBS were
      studies. Mean age of onset was 5 years. Male and female ratio was 1.4:1. History
      of antecedent infection was 73%. Clinical presentations included limb weakness
      100%, respiratory distress 27%, facial palsy 27%, autonomic nervous dysfunction
      22% and ataxia 17%. Nerve conduction study revealed demyelinating process in 57%,
      axonopathy in 26% and mixed type in 17%. Clinical outcomes were satisfactory in
      most of the patients except three patients who still had disability eighteen
      months after onset. Autonomic nervous dysfunction was a significant factor to
      determine the severity. CONCLUSION: The demographic and clinical features of GBS
      were similar to other published studies. The autonomic nervous dysfunction was a
      significant predictor for adverse clinical course. All but three patients had
      complete, full recovery.

PMID- 25391181
TI  - Survival analysis of Down syndrome with congenital heart disease: a 5-years
      registry at QSNICH.
AB  - BACKGROUND: Down syndrome (DS) is the most common chromosomal abnormality in
      children. Atrio-ventricular septal defect (AVSD) is the most common congenital
      heart disease (CHD) reported in DS. The mortality rate of DS with congenital
      heart disease (CHD) is 5-7 times higher than normal population. The survival rate
      in DS has improved with time and has reported up to 91% and 85% at one and ten
      years of age, respectively. OBJECTIVE: To study the prevalence of CHD, clinical
      course, treatment, the overall survival in patients with DS compare with those
      who are associated with CHD. STUDY DESIGNS: DS registry, multidisciplinary
      approach, single centre. MATERIAL AND METHOD: All DS patients at QSNICH with
      parental signed consent were enrolled in the registry. The study was conducted
      for 5 years starting from May 2007 to April 2012. All patients were followed-up
      according to schedule modified from American Academic of Pediatrics (AAP) health
      supervision guideline. Standard treatment was given to all those children with
      diagnosis of CHD and/or other associated diseases. RESULTS: Four hundred and two
      cases of DS were enrolled. Two cases were excluded due to the parental
      inconvenience. The mode and mean age of the patients at registration were 1 and 7
      months (1-62). Two hundred and seventy-one cases had an initial echocardiographic
      diagnosis of CHD, which included 91 of Patent ductus arteriosus (PDA), 49 of
      Ventricular septal defect (VSD), 34 of AVSD, 34 of secondum Atrial septal defect
      (ASD), 6 of Tetralogy of Fallot (TOF), 2 of Coractation of Aorta (CoA), 11 of
      other CHD and 44 of combined lesions. During the follow-up period, spontaneous
      closure of PDA, VSD and ASD occurred in 46, 12 and 15 cases, respectively. After
      the exclusion of those who had spontaneous closure, the prevalence rate of CHD in
      DS was 49.8%. VSD was the most common lesion, slightly more than PDA. Ninety
      eight cases underwent cardiac surgery; including 39 of associated VSD, 24 of
      AVSD, 26 of PDA, 3 of TOF, 4 of CoA/AA repaired, one each of Cor triatriatum and
      primum ASD. Twelve cases had catheter interventions, including PDA occlusion (10
      cases), and 1 case of balloon dilatation of re-CoA and coils embolization of
      isolated major aorto-pulmonary collateral artery. Seven cases were lost at follow
      up. By using the hospital information and National Health Security Office (NHSO)
      database, 47 infants died during the follow-up period. The causes of death were
      immediate post cardiac surgery in 10 cases (AVSD in 9, VSD in 1) and not
      associated with surgery in 37 cases including CHF in 8, pneumonia in 7, leukemia
      in 4, airway disease in 3, others 7 and unknown 8 cases. The overall survival at
      1 and 5 years of age were 96% and 86%, respectively. DS with CHD had a
      significantly lower survival rate than those without CHD (p < 0.001). CONCLUSION:
      According to this study, the prevalence rate of CHD in DS was high. VSD was the
      most common lesion and has better prognosis than AVSD. The main cause of death
      was a cardiac problem. Follow-up patients by using modified AAP guideline and
      standard treatment can improve their overall survival.

PMID- 25391182
TI  - Breast milk iodine concentrations in lactating mothers at Queen Sirikit National
      Institute of Child Health.
AB  - BACKGROUND: In Thailand, Iodine Deficiency Disorder (IDD) has been one of the
      most serious nutritional problems for over 50 years, especially for infants and
      young children. Iodine is an essential component of thyroid hormones, which are
      necessary for brain and body development especially during the first 2 years of
      life. During the first 6 months of life, infants receive iodine exclusively from
      breast or formula milk. Several national programs have been implemented to
      eliminate IDD. OBJECTIVE: To evaluate breast milk iodine concentrations in
      lactating mothers. MATERIAL AND METHOD: 100 lactating mothers from Lactation
      Clinic, Queen Sirikit National Institute of Child Health were included in this
      study from September 2011 to April 2012. Mothers completed questionnaires for
      analyzing demographic data and iodine intake. Samples of breast milk were
      collected to measure iodine content. RESULTS: The median value of breast milk
      iodine concentration was 129.7 mcg/L (IQR = 81.0, 205.7). Forty-two percent of
      the samples contained more than 150 mcg/L of iodine, which was in the range of
      sufficient iodine levels for infants. Factors relating to the iodine content in
      breast milk are baby's age, mother's age and mother's consumption of iodine
      fortified egg (p-value = 0.004, 0.035, 0.030, respectively). CONCLUSION: Iodine
      is essential for pregnant and lactating women, as well as infants. For mothers,
      consumption of iodized salt, iodized fish sauce, and iodine fortified food can
      improve iodine status of mothers. For infants, initiating breastfeeding soon
      after birth and maintaining exclusive breastfeeding can help infants achieve
      optimal nutritional status.

PMID- 25391183
TI  - Quality of life in adolescent absence epilepsy at Queen Sirikit National
      Institute of Child Health.
AB  - OBJECTIVE: To compare the QoL between adolescents with absence epilepsy and the
      other types of epilepsies. MATERIAL AND METHOD: A prospective cohort study was
      conducted in adolescents aged 10-18 years that have been diagnosed with epilepsy
      at QSNICH between 2000 and 2012. The QoL was assessed using the QoLIE-AD-48, Thai
      version. RESULTS: Seventy-three adolescents were included in this study, of which
      27 had absence epilepsy. The mean total QoLIE-AD-48 score was 63.94 (17.14). The
      absence group had a mean score of 74.45 (9.83), while the non-absence group had a
      score of 57.78 (17.57), p-value < 0.001. CONCLUSION: The QoL of adolescents with
      inactive absence epilepsy was significantly higher than those suffering with
      other types of epilepsy. The QoL in this study was similar to prior studies.

PMID- 25391184
TI  - Clinical characteristics and cost of chickenpox hospitalization in Thai children.
AB  - BACKGROUND: Although primary Varicella-Zoster-Virus (VZV) infection generally
      causes uncomplicated illness confined to skin and mucous membrane among healthy
      children, it infrequently causes life-threatening infection especially among
      immuno-suppressed hosts or young infants. Limited information is available
      regarding the clinical features, outcomes, and the financial burden incurred by
      severe primary varicella infection in Thai children who required hospitalization.
      OBJECTIVE: To determine clinical characteristics particularly the disease
      severity, prevalence of complication, case fatality rate, and use of healthcare
      resources in terms of length of stay as well as direct medical cost of varicella
      associated hospitalization in children. MATERIAL AND METHOD: A retrospective
      descriptive study was conducted among children aged one month to 18 years who
      were hospitalized with chickenpox between 2007 and 2011 at the Queen Sirikit
      National Institute of Child Health, Bangkok, Thailand. Information on clinical
      manifestations, complications, and outcomes were obtained by medical record
      abstraction, and data on hospital charges were obtained from the hospital
      financial database. RESULTS: A total of 101 cases of chickenpox were identified,
      with a median (interquartile range IQR) age of 4 (0.8, 7.25) years. Underlying
      predisposing conditions for severe varicella infection were identified in 35
      cases (34.7%). Seventy four of 101 (73.3%) patients developed complications, with
      skin and soft tissue infections being the most common (50.5%), followed by
      pneumonia (12.7%) and neurological complications (6.4%). There were no fatal
      cases. Median (IQR) duration of hospitalization and hospital charges were 6 (3,
      9) days and US$ 330.2 ($139.3, $1,013.5), respectively. Children with
      predisposing conditions for severe varicella were significantly older, incurring
      6-fold higher hospital charges and 2-fold longer hospitalization compared to
      their counterparts. CONCLUSION: The high rate of complicated varicella and
      financial burden reported in this study suggested that the severity of varicella
      complications in children might have been previously underestimated. This study
      provides relevant information regarding the burden of hospitalized varicella
      infection among both otherwise healthy children as well as children with
      predisposing immuno-suppression.

PMID- 25391185
TI  - Human papillomatosis genotyping and severity in patients with recurrent
      respiratory papillomatosis.
AB  - BACKGROUND: Recurrent respiratory papillomatosis (RRP) is caused by human
      papilloma virus (HPV) and is the most common benign laryngeal neoplasm in
      children. Although RRP is rarely fatal, the disease requires prolonged, extensive
      medical and surgical treatment, leading to physical and emotional suffering in
      affected children and their families. Previous studies show HPV type 11 and type
      6 in the lesion of Thai subjects with RRP. There is currently no published data
      available from Thailand that compares staging and severity with RRP genotypes.
      OBJECTIVE: To identify the genotypes of human papilloma virus (HPV) isolated from
      patients with RRP and compare the staging and severity with human papilloma virus
      genotype. MATERIAL AND METHOD: This prospective study was designed to assess
      population characteristics and follow the clinical course of RRP from January
      2011 to January 2013. At each endoscopic evaluation or debridement, all surgeons
      to stage each patient's disease severity used a consistent scoring system. The
      samples were analyzed for HPV genotype. RESULTS: Fifteen Thai children (7 female,
      8 male) with respiratory papillomatosis were enrolled. Results showed that HPV
      type 6 and HPV type 11 caused RRP in 6 (40%) and 9 (60%) of the children,
      respectively. No co-infection between HPV type 6 and type 11 was found. Overall
      mean age at diagnosis of patients with RRP was 2.65 +/- 0.82 years. The age at
      diagnosis was significantly different between both HPV genotypes (p = 0.008). The
      mean disease severity score for HPV type 6 infection was 13.83 +/- 9.94, and that
      of HPV type 11 infection was 27.44 +/- 8.24. The mean disease severity score of
      HPV type 11 infection was significantly higher than that of HPV type 6 infection
      (p = 0.013). CONCLUSION: HPV type 6 and type 11 caused RRP in Thai children. RRP
      attributable to infection with HPV type 11 is more aggressive in disease severity
      and has a shorter life time than HPV type 6 at time of first diagnosis. RRP is an
      incurable disease that requires long-term medical management. Improved awareness
      and understanding amongst the Thai population should be promoted to limit the
      spread of the disease. In addition, further research on the treatment of RRP
      would benefit patients.

PMID- 25391186
TI  - Review of mucopolysaccharidosis diseases at the Queen Sirikit National Institute
      of Child Health in the past 15 years.
AB  - BACKGROUND: Mucopolysaccharidosis (MPS) can be classified into 7 types according
      to the enzyme defects. Several countries use enzyme replacement therapy (ERT) as
      treatment for types 1, 2 and 6. ERT is very expensive:--therefore, to determine
      if this treatment could be made available in Thailand, it is important to know
      the numbers of the patients with MPS. OBJECTIVES: To investigate the number and
      clinical profiles of MPS patients who visited the Queen Sirikit National
      Institute of Child Health (QSNICH) to determine the incidence of MPS in Thailand.
      MATERIAL AND METHOD: Review of MPS patients' medical records with confirmed
      diagnosis by enzyme tests, who visited QSNICH from January 1999 to December 2013.
      RESULTS: Medical records showed that 22 MPS patients visited QSNICH during the
      past 15 years. Of these patients, 5 were MPS 1 patients (intermediate type or
      Hurler-Scheie syndrome), 8 were MPS2 patients (severe form), 1 was a MPS3
      patient, 2 were MPS4 patients and 6 were MPS6 patients (severe form). The first
      clinical sign observed in MPS1 is joint contracture, whereas in MPS2 is delayed
      development. For MPS2, all except one patient had macrocephaly (head
      circumference is more than 90 percentile). Other growth parameters, including
      weight and height, in MPS2 patients were higher than average (> 50 percentile).
      CONCLUSION: MPS2 is the most common type of MPS in this study, followed by type 6
      and 1. The difference in growth parameters seen in MPS2 suggest that it may be a
      factor in the development of MPS2.

PMID- 25391187
TI  - Double-balloon aortic valvuloplasty at Queen Sirikit National Institute of Child
      Health.
AB  - BACKGROUND: Balloon aortic valvuloplasty is the treatment of choice in moderate
      and severe valvular aortic stenosis. In order to reduce the risk of vascular
      complications, a double-balloon technique has been used with good results.
      OBJECTIVE: To present the results od double-balloon aortic valvuloplasty at
      QSNICH. MATERIALS AND METHOD: Consecutive cases of severe valvular aortic
      stenosis treated with double-balloon aortic valvuloplasty at QSNICH were
      recruited in the study. Data were obtained from the medical records starting from
      the day of presentations to December 2011. RESULTS: There were six cases of
      severe valvular aortic stenosis treated with double-balloon aortic valvuloplasty
      at QSNICH from 2004 to 2011. The age and weight ranged from 7 months to 12 years
      and 6 to 53.8 kilograms, respectively. The presenting symptoms were dyspnea in 3
      (50%) and asymptomatic heart murmur in 3 cases (50%). Peak-to-peak pressure
      gradient (PG) before the procedure ranged from 48-104 mmHg (mean 70.00, SD 18.92
      mmHg). Immediately after the procedure, PG significantly decreased to 15-52 mmHg
      (mean 34.33, SD 14.98 mmHg, p < 0.01). On the following day after the procedure,
      peak instantaneous pressure gradient (PIPG) obtained from echocardiogram ranged
      from 17-47 mmHg (mean 36.50, SD 10.93 mmHg). PIPG were not significantly
      different from PG immediately after valvuloplasty. There were two cases with
      partial femoral occlusion. The duration of follow-up ranged from 6-54 months
      (median 24 months). In the follow-up period, all of the patients were
      asymptomatic with functional class I. Echocardiogram after the procedure revealed
      no significant aortic regurgitation in any of the cases. CONCLUSION: Double
      balloon aortic valvuloplasty can be performed safely with very good intermediate
      term outcome in selected patients. Long-term outcome in Thai children should be
      further studied.

PMID- 25391188
TI  - Clinical abnormalities, early intervention program of Down syndrome children:
      Queen Sirikit National Institute of Child Health experience.
AB  - OBJECTIVE: Queen Sirikit National Institute of Child Health is a tertiary
      institute of children in Thailand, where early intervention programs have been
      provided since 1990 by multidisciplinary approach especially in Down syndrome
      children. This aim of the present study is to follow the impact of early
      intervention on the outcome of Down syndrome children. The school attendance
      number of Down syndrome children was compared between regular early intervention
      and non-regular early intervention. MATERIAL AND METHOD: The present study group
      consists of 210 Down syndrome children who attended early intervention programs
      at Queen Sirikit National Institute of Child Health between June 2008 and January
      2012. Data include clinical features, school attendance developmental quotient
      (DQ) at 3 years of age using Capute Scales Cognitive Adaptive Test/Scale
      (CAT/CLAMS). Developmental milestones have been recorded as to the time of
      appearance of gross motor, fine motor, language, personal-social development
      compared to those non-regular intervention patients. RESULTS: Of 210 Down
      syndrome children, 117 were boys and 93 were girls. About 87% received regular
      intervention, 68% attended speech training. Mean DQ at 3 years of age was 65. Of
      the 184 children who still did follow-up at developmental department, 124
      children (59%) attended school: mainstream school children 78 (63%) and special
      school children 46 (37%). The mean age at entrance to school was 5.8 +/- 1.4
      years. The school attendance was correlated with maternal education and regular
      early intervention attendance. CONCLUSION: Regular early intervention starts have
      proven to have a positive effect on development. The school attendance number of
      Down syndrome children receiving regular early intervention was statistically and
      significantly higher than the number of Down syndrome children receiving non
      regular early intervention was. School attendance correlated with maternal
      education and attended regularly early intervention. Regular early intervention
      together with maternal education are contributing factors influencing school
      attendance in Down syndrome children in the present study

PMID- 25391189
TI  - Bronchoscopic findings in Down syndrome children with respiratory problems.
AB  - BACKGROUND: Down syndrome (DS) can affect the upper and lower respiratory tract
      in a number of ways and disorders of other systems can impact upon respiratory
      function, giving rise to a wide variety of respiratory manifestations. OBJECTIVE:
      To investigate the frequency, associated conditions, and type of airway anomalies
      in DS children with respiratory problems. MATERIAL AND METHOD: Twenty-nine
      children with DS were evaluated for airway anomalies, with indications of
      atelectasis, stridor, and recurrent or persistent pneumonia, using flexible
      fiberoptic bronchoscopy (FB). The children were assessed retrospectively.
      RESULTS: Results showed high frequency of associated conditions, which was found
      in 19 children. The most common associated condition was congenital heart
      disease. Other associated conditions were hypothyroid and duodenal atresia.
      Endoscopic findings showed several airways anomalies, including laryngomalacia,
      tracheal bronchus, and subglottic stenosis. Three patients had multiple airway
      anomalies and three had normal endoscopic findings. CONCLUSION: DS children with
      respiratory problems have high frequency of airway anomalies and FB, which is a
      useful diagnostic procedure. A thorough understanding of the airway anomalies
      will aid in the evaluation and management of DS children with respiratory
      problems.

PMID- 25391190
TI  - Pilot study on growth parameters and nutritional biochemical markers in very low
      birth weight preterm infants fed human milk fortified with either human milk
      fortifier or post discharge formula.
AB  - BACKGROUND: Nutrition is an important aspect in the care of very low birth weight
      (VLBW) preterm infants. Human milk fortified with human milk fortifiers (HMF) is
      best for enteral feeding of premature infants. HMF is expensive and not easily
      available in Thailand. Post discharge formula (PDF) has been routinely used to
      fortify human milk at Queen Sirikit National Institute of Child Health (QSNICH)
      but there is lack of supportive data regarding efficacy and safety. OBJECTIVE: To
      study and compare anthropometrics, biochemical markers and complications in VLBW
      infants fed human milk fortified with either HMF or PDF. MATERIAL AND METHOD:
      This was a prospective, randomized pilot study conducted in the neonatal unit of
      QSNICH from 1 March 2010 to 28 February 2011. Very low birth weight neonates,
      whose mothers had adequate breast milk within 96 hours of birth, were enrolled in
      the study and received parenteral nutrition and enteral feeding as per protocol.
      Once the babies were feeding 100 cc/kg/day of human milk, they were randomly
      divided into two groups: the human milk fortified group (HMF group) and the post
      discharge formula fortified group (PDF group). Body weight was recorded daily
      while head circumference and length were recorded weekly. Hematocrit, Blood Urea
      Nitrogen (BUN), creatinine, electrolytes (including phosphorus and calcium),
      alkaline phosphatase and albumin were checked at the beginning of the study
      (feeding 100 cc/kg/day), 3 weeks later and when on full oral breast feeding or
      reached a weight of 2,000 grams, which ever came first. RESULTS: Thirty-eight
      infants were enrolled in the study but eventually only 33 remained (18 in HMF
      group, 15 in PDF group). Both groups had similar baseline demographic data,
      nutritional management, postnatal morbidities and length of stay. There were no
      statistically significant differences in growth parameters and serum biochemical
      markers between the groups. Definite NEC was not different between the groups.
      Other complications of prematurity including osteopenia of prematurity were
      similar in both the groups. The cost of breast milk fortification per person in
      the PDF and HMF group was 605 and 11,655 baht, respectively. CONCLUSION: Human
      milk fortifiers are best for fortification of human milk in VLBW babies but using
      PDF as a fortifier may be considered as an alternative for VLBW infant in
      resource limited, developing countries. However, it should always be additionally
      supplemented with multivitamins especially vitamin D, iron, calcium and
      phosphorus. Complications like feeding intolerances and suspected NEC should be
      monitored closely. Larger studies focusing on short and long-term outcomes are
      needed in the future.

PMID- 25391191
TI  - An unusual cause of progressive cyanosis post Fontan operation: congenital extra
      hepatic porto-systemic shunt.
AB  - OBJECTIVE: To report an unusual case of progressive cyanosis post Fontan
      operation due to porto-systemic venous shunt and the result of its treatment.
      MATERIAL AND METHOD: A patient with diagnosis of progressive cyanosis post Fontan
      operation from porto-systemic venous shunt at QSNICH RESULTS: This is a case of
      twelve years old girl, who had diagnosis of situs solitus, levocardia, atrio
      ventricular concordant, ventriculo-arterial concordant, hypoplastic right
      ventricle with large ventricular septal defect. She had pulmonary artery banding
      at 4 months of age followed by a non-fenestrated extra-cardiac conduit Fontan
      performed at 7 years and 7 months of age. During the first year of post
      operation, her systemic oxygen saturation (SpO2) was 93-94% after which it
      decreased to 87%, 84%, 75% at 1.5, 2.5 and 3 years after surgery, respectively.
      Clinically she also had progressive dyspnea on exertion. Diffuse pulmonary
      arterio-venous malformation was demonstrated by contrast echocardiogram during
      cardiac catheterization. Cardiac magnetic resonance angiography showed abnormal
      extra-hepatic portal vein to inferior vena cava shunt. After balloon test
      occlusion in the cath lab, which showed no change in the portal venous pressure,
      complete occlusion of this porto-systemic venous shunt was performed by using
      Amplatzer Vascular Plug II. Her systemic oxygen saturation increased to 83% with
      functional class I at one-year post occlusion. CONCLUSION: The present report an
      unusual case of progressive cyanosis post Fontan operation due to pulmonary
      arteriovenous malformation, which was secondary to congenital extra-hepatic porto
      systemic shunt. The venous blood from the intestinal and splenic veins was
      partially bypassing the liver into inferior vena cava. The patient's clinical
      condition and SpO2 improved after transcatheter occlusion of the shunt with the
      device.

PMID- 25391192
TI  - Establishing of National Birth Defects Registry in Thailand.
AB  - BACKGROUND: Deaths attributed to birth defects are a major cause of infant and
      under-five mortality as well as lifetime disabilities among those who survive. In
      Thailand, birth defects contribute to 21% of neonatal deaths. There is currently
      no systematic registry for congenital anomalies in Thailand. Queen Sirikit
      National Institute of Child Health has initiated a Thailand Birth Defects
      Registry to capture birth defects among newborn infants. OBJECTIVE: To establish
      the national birth defects registry in order to determine the burden of birth
      defects in Thailand. MATERIAL AND METHOD: The birth defects data come from four
      main sources: National Birth Registry Database; National Health Security Office's
      reimbursement database; Online Birth Defect Registry Database designed to capture
      new cases that were detected later; and birth defects data from 20 participated
      hospitals. All data are linked by unique 13-digit national identification number
      and International Classification of Diseases (ICD)-10 codes. This registry
      includes 19 common structural birth defects conditions and pilots in 20
      hospitals. The registry is hospital-based, hybrid reporting system, including
      only live births whose information was collected up to 1 year of age. RESULTS:
      3,696 infants out of 67,813 live births (8.28% of total live births in Thailand)
      were diagnosed with congenital anomalies. The prevalence rate of major anomalies
      was 26.12 per 1,000 live births. The five most common birth defects were
      congenital heart defects, limb anomalies, cleft lip/cleft palate, Down syndrome,
      and congenital hydrocephalus respectively. CONCLUSION: The present study
      established the Birth Defects Registry by collecting data from four databases in
      Thailand. Information obtained from this registry and surveillance is essential
      in the planning for effective intervention programs for birth defects. The
      authors suggest that this program should be integrated in the existing public
      health system to ensure sustainability.

PMID- 25391193
TI  - Pilot study in young Thai children with delayed bottle-weaning at Queen Sirikit
      National Institute of Child Health: does it affect iron status?
AB  - BACKGROUND: Delayed bottle weaning or prolonged bottle-feeding affects the
      child's health. Many studies found the increased incidence of dental caries,
      obesity, and iron deficiency anemia (IDA) among these children. IDA is one of the
      health problems found in Thai children that reflects both poor health and
      malnutrition. The Royal College of Pediatricians of Thailand has recommended that
      parents wean bottle-feeding when children reach the age of 1 to 11/2 years old.
      However, previous studies reported that only 8% of 1,038 Thai children aged 1-2
      years successfully discontinued bottle-feeding. Therefore, we were interested to
      investigate parental knowledge and iron status in Thai children with prolonged
      bottle-feeding. OBJECTIVE: To evaluate parental knowledge of bottle weaning and
      iron status in Thai children aged 11/2 to 2 years who were still bottle-fed.
      MATERIAL AND METHOD: A cross-sectional descriptive study was performed in 30
      children who were bottle-fed, aged 11/2 to 2 years, at Well-Child Clinic, Queen
      Sirikit National Institute of Child Health during the period of February 3rd
      October 9th, 2012. The parents were interviewed using questionnaires on the
      practices and knowledge of bottle-feeding. Blood samples were collected for
      ferritin levels and complete blood count. RESULTS: The average age of the 30
      children, who were still bottle-fed, was 19.3 +/- 1.5 months old. The primary
      caregivers were parents living in Bangkok. All of the parents finished Bachelor's
      degree or higher. Almost all of the caregivers (28/30) of unweaned children
      understood that bottle weaning was recommended for children aged 12-18 months
      old, and the food recommendation for a one-year-old child was 3 meals of food and
      2-3 meals of milk per day. Blood samples showed iron deficiency in 43% of the
      children with delayed bottle weaning, which included 7% oF IDA. CONCLUSION:
      Delayed bottle weaning in young children was related to iron depletion.

PMID- 25391194
TI  - Effect of folic acid supplementation on plasma homocysteine in obese children: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Obese children tend to consume less dietary folate, which is an
      important cofactor in remethylation of homocysteine to methionine. The deficiency
      of folate can lead to hyperhomocysteinemia. OBJECTIVE: To determine whether folic
      acid supplementation could reduce plasma homocysteine in obese children. MATERIAL
      AND METHOD: Obese children, aged 9-15 years with body mass index > median plus 2
      SD according to WHO reference, were randomly assigned to 2 groups: receiving
      either 5 mg folic acid or placebo for 2 months. Fasting homocysteine, creatinine,
      folate, vitamin B12, insulin, glucose and lipid profiles were taken at baseline
      and the end of the study. Dietary vitamin B12, folate intake and physical
      activity were assessed using validated questionnaires. RESULTS: Fifty obese
      children (31 boys and 19 girls) took part in the study. Their mean age was 10.9
      +/- 1.6 years and mean BMI Z-score was 3.41 +/- 0.69. After the intervention,
      plasma homocysteine decreased by 15.75% and 6.99% in the folic acid and placebo
      group, respectively (mean difference 8.76%; 95% CI: 0.26%, 17.25%, p = 0.044).
      This divergence was more pronounced in boys and it remained significant after
      adjusting for baseline homocysteine and other confounders. Subgroup analysis
      showed a larger magnitude of plasma homocysteine reduction in the low folate
      group (mean difference 12.24%; 95% CI: 1.39%, 23.09%). CONCLUSION: The
      homocysteine lowering effect of folic acid supplementation was found in obese
      children, especially in boys and those with low serum folate. Further long-term
      interventional studies are needed to determine the effects of the lowered plasma
      homocysteine on the cardiovascular outcomes of obese children. This trial was
      registered on clinicaltrials.gov (NCT01766310).

PMID- 25391195
TI  - Outcomes of straightforward extracardiac Fontan operation in advanced-age group.
AB  - INTRODUCTION: Fontan operation is a palliative procedure used in patients with
      univentricular heart (UVH). There have been numerous modifications to the
      technique. The appropriate strategy for treating patients with UVH in Thailand is
      still a major concern. OBJECTIVE: To describe the outcomes of patients after
      straightforward Fontan operation at advanced-age and evaluate their post-surgical
      cardiac performance. MATERIAL AND METHOD: A cross sectional study was performed
      in post-Fontan operation patients at Rajvithi Hospital between 2000 and 2009.
      Post-operative cardiac performance was analyzed using the echocardiogram and
      treadmill exercise stress test (EST). RESULTS: Thirty-nine patients were enrolled
      in the present study. The mean age was 11.7 years and the mean age at operation
      was 7.4 years. The predominant systemic chamber was morphologic left ventricle.
      Straightforward Fontan operation was performed in 60% of cases. Mean of Fontan
      index, mean of McGoon ratio, and mean of Nakata index were 2.63, 2.32, and 414.15
      sqmm/sqm, respectively. Mean of the PVR and PAP were 1.98 U/m2 and 11.05 mmHg.
      Eighteen percent of patients died in the early post-operative period. Most of the
      patients died from septicemia. The mean EFwas 58.43%. Systolic dysfunction in
      17.9% of the cases was abnormal, whereas diastolic dysfunction was present in
      half of the cases. Thirty-nine percent had MPI abnormality. During EST three
      cases developed arrhythmias and 3 cases had hypotension. Patients were
      categorized into 3 groups (Group 1: normal systolic and diastolic functions,
      Group 2: diastolic dysfunction, Group 3: impairment of both systole and
      diastole). Pre-operative cardiac catheterization parameters, surgical data and
      cardiac performance showed no statistical significance. However, there was a
      significant correlation between those with abnormal cardiac performance and
      arrhythmias or hypotension during EST (p = 0.003). CONCLUSION: The selection of
      suitable cases and good pre-operative evaluation could decrease the morbidity and
      mortality in patients undergoing the Fontan procedure. This study also found a
      correlation between abnormal cardiac performance and transient cardiac arrhythmia
      during exercise. The evaluation of cardiac performance and EST remains to be
      performed for following-up of patients who have undergone the Fontan operation,
      even for the asymptomatic cases.

PMID- 25391196
TI  - Effects of the use of multi-layer filter on radiation exposure and the quality of
      upper airway radiographs compared to the traditional copper filter.
AB  - BACKGROUND: The problem of image quality in a large number of upper airway
      obstructed patients is the superimposition of the airway over the bone of the
      spine on the AP view. This problem was resolved by increasing KVp to high KVp
      technique and adding extra radiographic filters (copper filter) to reduce the
      sharpness of the bone and increase the clarity of the airway. However, this
      raises a concern that patients might be receiving an unnecessarily higher dose of
      radiation, as well as the effectiveness of the invented filter compared to the
      traditional filter. OBJECTIVE: To evaluate the level of radiation dose that
      patients receive with the use of multi-layer filter compared to non-filter and to
      evaluate the image quality of the upper airways between using the radiographic
      filter (multi-layer filter) and the traditional filter (copperfilter). MATERIAL
      AND METHOD: The attenuation curve of both filter materials was first identified.
      Then, both the filters were tested with Alderson Rando phantom to determine the
      appropriate exposure. Using the method described, a new type of filter called the
      multi-layer filter for imaging patients was developed. A randomized control trial
      was then performed to compare the effectiveness of the newly developed multi
      layer filter to the copper filter. The research was conducted in patients with
      upper airway obstruction treated at Queen Sirikit National Institute of Child
      Health from October 2006 to September 2007. A total of 132 patients were divided
      into two groups. The experimental group used high kVp technique with multi-layer
      filter, while the control group used copper filter. A comparison of film
      interpretation between the multi-layer filter and the copper filter was made by a
      number of radiologists who were blinded to both to the technique and type of
      filter used. RESULTS: Patients had less radiation from undergoing the kVp
      technique with copper filter and multi-layer filter compared to the conventional
      technique, where no filter is used. Patients received approximately 65.5% less
      radiation dose using high kVp technique with multi-layer filter compared to the
      conventional technique, and 25.9% less than using the traditional copper filter
      45% of the radiologists who participated in this study reported that the high kVp
      technique with multi-layer filter was better for diagnosing stenosis, or
      narrowing of the upper airways. 33% reported that, both techniques were equal,
      while 22% reported that the traditional copper filter allowed for better details
      of airway obstruction. These findings showed that the multi-layered filter was
      comparable to the copper filter in terms of film interpretation. CONCLUSION:
      Using the multi-layer filter resulted in patients receiving a lower dose of
      radiation, as well as similar film interpretation when compared to the
      traditional copper filter.

PMID- 25391197
TI  - Serum lactate and lactate dehydrogenase as parameters for the prediction of
      dengue severity.
AB  - BACKGROUND: Lactate and lactate dehydrogenase (LDH) have been found to be
      elevated in cardiopulmonary failure, sepsis, shock and hepatic injury. Severe
      dengue hemorrhagic fever (DHF) patients also develop shock and experience a
      certain degree of hepatic injury, implicating that serum lactate and LDH may be
      elevated in Dengue shock syndrome (DSS). OBJECTIVE: To determine serum lactate
      and LDH levels in dengue patients to see whether they can be used as predictors
      of severe dengue cases. MATERIAL AND METHOD: A cross sectional study was
      conducted on suspected dengue patients admitted to the dengue ward, Queen Sirikit
      National Institute of Child Health (QSNICH), between May 2011 and February 2012.
      Laboratory tests were used to confirm dengue cases in the enrolled patients.
      Blood for serum lactate was drawn in patients every day after enrollment. Blood
      for LDH and liver function test (LFT) were drawn 3 times: enrollment day, day of
      leakage, and discharge day. Lactate and LDH levels are compared among dengue and
      non-dengue patients. Dengue fever (DF), DHF and DSS patients were classified
      according to the WHO 1997 dengue classification. RESULTS: 253 patients were
      enrolled, comprising of 120 DF, 75 DH, 30 DSS, and 28 non-dengue patients. The
      majority of dengue patients had liver impairment, demonstrated by elevated
      aspartate aminotransferase (AST) (94.9%) and alanine aminotransferase (ALT)
      levels (68.6%) while non-dengue patients have minimal elevation. Serum lactate
      levels were not elevated in the early stages in dengue patients, but were
      elevated in non-dengue patients. The mean serum lactate levels in DSS patients
      increased towards the end of febrile phase and reached maximum values on Day 0
      (2.2 U/L). On the other hand, serum lactate levels were found to be decreasing in
      the non-dengue group. The mean serum lactate levels on Day 0 was found to be
      different in DSS patients (2.26 U/L) compared to DF 1.63 U/L), DHF (1.79 U/L) and
      non-dengue patients (1.68 U/L) (p < 0.05). Mean serum LDH levels were elevated in
      the early stages of the disease in all groups of patients, but with different
      levels. Mean serum LDH levels was 709.2 in DF, 1,873 in DHF, 654.5 in DSS, and
      434 IU in non-dengue patients. The mean LDH levels in dengue patients were > 500
      IU, while it was < 500 IU in non-dengue patients. The increasing mean levels of
      LDH towards the end of febrile phase were only seen in DHF and DSS patients, but
      not in DF and non-dengue patients. The mean levels of LDH on Day 0 in DHF, DSS,
      DF and non-dengue patients are 1,060.7, 1,180.7, 787.2, and 423.8 IU,
      respectively. CONCLUSION: Serum lactate and LDH was found to be elevated in DHF
      and/or DSS patients. Lactate may be used as a predictor of DSS if the level is >
      2 U/L on Day 0. LDH can be used to differentiate patients with or without dengue
      in the early febrile phase, if the level is > 500 IU. If the level of LDH is
      increased to approximately 1, 000 IU on Day 0, it may be a predictor of severe
      dengue infection or DHF and DSS with plasma leakage.

PMID- 25391198
TI  - A comparative study: right ventricular assessment in post-repaired tetralogy of
      Fallot patients by echocardiogram with cardiac magnetic resonance imaging.
AB  - BACKGROUND: Post-repaired Tetralogy of Fallot (TOF) patients require
      comprehensive evaluation of the right ventricular (RV) size and function.
      Currently, cardiac magnetic resonance imaging (CMR) is considered to be the gold
      standard for RV function assessment. Echocardiogram (ECHO) is the most useful non
      invasive tool for RV assessment. However, correlations of ECHO and CMR findings
      for this particular group of patients require further evaluation. OBJECTIVE: The
      first objective is to assess the correlation between RV size/function, measured
      by ECHO and CMR. The second objective is to investigate ECHO parameters that
      correlate best with RV end diastolic volume index (RVEDVi) of 160 mL/m2 from CMR.
      MATERIAL AND METHOD: The present study recruited 20 TOF patients (mean age 14 +/-
      2 years) who underwent right ventricular outflow tract reconstruction and/or
      pulmonary valve replacement for at least 5 years, from June 2011 to March 2012.
      The RV was initially evaluated with CMR, followed by ECHO within 3 months. ECHO
      parameters measured were tricuspid annular plane systolic excursion (TAPSE),
      fractional area change (FAC), area of right ventricular end diastole index (area
      RVEDi), RV free wall myocardial performance index (RVMPI), and qualitative
      assessment of pulmonary valve regurgitation (PR). All ECHO parameters were
      compared with CMR measurements of right ventricular ejection fraction (RVEF),
      RVEDVi and quantitative assessment of PR. Comparative analysis were assessed by
      Pearson's sample correlation coefficient, Kappa, and sensitivity and specificity
      of RVEDi area from ROC curve analysis. RESULTS: Results showed significant
      correlations between RVEDVi and area RVEDi (R = 0.768, p < 0.01), RVEF with FAC
      (R = 0.759, p < 0.01), and RVEF with TAPSE (R = 0.688, p < 0.01). Hundred percent
      correlation was found in moderate to severe PR assessment by ECHO and CMR (Kappa
      = 0.912). Abnormal RVMPI was not correlated with NYHA FC, CXR and ECG (Kappa = 
      0.10, 0.15, -0.04). The area RVEDi >= 20.43 cm2/m2 correlated well with RVEDVi >=
      160 mL/m2 (sensitivity 64%, specificity 83%) from ROC curve analysis. CONCLUSION:
      ECHO is an effective tool for RV evaluation in post-repaired TOF with PR. FAC,
      TAPSE and severity of PR from ECHO correlated well with CMR parameters.
      Measurement of area RVEDi from ECHO is the best parameter to predict RVEDVi from
      CMR.

PMID- 25391199
TI  - Rare epileptic syndrome of ring chromosome 20 with epileptic encephalopathy: a
      case report.
AB  - The authors report the clinical features, electroencephalography (EEG),
      neuroimaging (brain magnetic resonance image-MRI), and cytogenetic findings of a
      young female patient with rare cytogenetic anomalies characterized by de novo 46,
      XX, r (20) (p13q13.3). The patient had a history of mild mental retardation,
      emotional liability and intractable epilepsy with non-convulsive status
      epilepticus. The MRI brain showed focal cerebral dysplasia over the left temporal
      region. The multiple seizures were refractory to antiepileptic medications and
      prolonged, confused state with or without a motor component. The continuous video
      EEG monitor showed epileptiform discharges over bilateral frontal regions with
      frontal origin. The symptoms were relieved after midazolam infusion. A patient
      who was present with intractable epilepsy with continuous frontal epileptiform
      discharges, mental retardation, abnormal behavior, without dysmorphic features
      should be suspected of chromosomal abnormalities especially ring chromosome 20.

PMID- 25391200
TI  - Application of fluoride tray for treatment of tongue biting in a Wilms' tumor
      child: a case report.
AB  - OBJECTIVE: To describe the successful intervention with a ready-made fluoride
      tray for treatment of severe tongue biting problem in a 3-year-old Wilms' tumor
      child admitted in Surgical Intensive Care Unit (SICU). MATERIAL AND METHOD: The
      medical record of a tongue biting Wilms' tumor child was retrospectively
      reviewed. RESULTS: The outcome was complete healing and regaining of normal
      tongue size and function without any complication. At the follow-up, the patient
      could talk and swallow normally. CONCLUSION: Ready-made fluoride trays as mouth
      guard can be successful in cases where patients are unable to have a custom-made
      mouth guard due to severe tongue protrusion. It could also be applied to similar
      situations and should be considered as another alternative treatment.

PMID- 25391201
TI  - Subcutaneous zygomycosis in children: 2 case reports.
AB  - Basidiobolus ranarum is an uncommon subcutaneous zygomycosis mostly found in
      immunocompetent children in tropical countries. Presence of slow growing non
      tender, non-inflammatory, subcutaneous swelling that does not spread beyond the
      subcutaneous tissue are classic clinical features. The authors report two cases
      of subcutaneous zygomycosis which tissue cultures were positive for Basidiobolus
      ranarum. The first case was a 10-months-old boy presented with prolonged high
      fever and a rapidly expanding ulcerated plaque unresponsive to systemic
      antibiotic. The second case was a 2-years-old girl presented with slow expanding
      mass at the buttock. Histopathology of both cases showed lobular panniculitis
      with eosinophilic infiltration and fungal culture revealed Basidiobolus ranarum.
      Oral itraconazole was given with good clinical response in both cases.

PMID- 25391202
TI  - Our new future.

PMID- 25391203
TI  - Current diagnosis and management of multiple myeloma.
AB  - The availability of a wide variety of treatments for multiple myeloma allows
      healthcare providers to tailor treatments to individual patient needs, and has
      enabled prolonged survival of patients with the disease. Improved understanding
      of the disease, its treatment options, and potential side effects of therapy has
      provided unique opportunities for oncology nurses to employ preventive
      approaches, care strategies, and patient and family education and support over
      time. Because therapies have been developed that prolong the survival time,
      people with multiple myeloma are in the position of living with the disease for
      many years. Additional challenges are presented as healthcare providers develop
      wellness and quality of life plans of care in the setting of multiple myeloma
      survivorship. This article will explore the diagnosis, treatment planning, and
      clinical management of patients with multiple myeloma.

PMID- 25391204
TI  - Advances and new challenges in multiple myeloma.

PMID- 25391205
TI  - Cognitive impairment in older adults with cancer.

PMID- 25391206
TI  - An infusion reaction to cetuximab.

PMID- 25391207
TI  - Ginseng.

PMID- 25391208
TI  - Denosumab, a rank ligand inhibitor for prevention of skeletal-related events due
      to bone metastases from solid tumors in adults.

PMID- 25391209
TI  - Letter from the Editor.

PMID- 25391210
TI  - The use of vegetables in the biomonitoring of cadmium and lead pollution in the
      environment.
AB  - Lead and cadmium emitted from various anthropogenic sources have the ability to
      accumulate in tissues of living organisms. The phenomenon of accumulation of
      metals in the body is harmful and undesirable. The ability of plants to
      accumulate heavy metals from the individual elements of the environment has been
      used in biomonitoring of pollution. Leaves and roots of vegetables have
      particular predisposition for accumulating toxic metals such as lead and cadmium
      and therefore can be used for biomonitoring of the environment, mainly as a tool
      for assessing the extent of soil contamination. The article discusses information
      in the literature on entry paths of lead and cadmium into the body, toxic effects
      of lead and cadmium on the human organism, and the use of vegetables as a tool in
      the biomonitoring of heavy metals in different elements of the environment. 

PMID- 25391211
TI  - A critical review of properties of darunavir and analytical methods for its
      determination.
AB  - Darunavir is a synthetic non-peptidic protease inhibitor that has been shown to
      be extremely potent against wild-type HIV, and it is an important component of
      highly active antiretroviral treatment (HAART), which is considered as one of the
      most significant advances in the field of HIV therapy. However, there are some
      concerns about darunavir quality control. Darunavir shows pseudo-polymorphism: in
      different ambient conditions one pseudo-polymorphic form can change to another.
      This behavior of darunavir is problematic because the dosage form is exposed to
      different ambient conditions around the world, since HIV/AIDS is prevalent
      globally. Issues around differences in the solubility and effects that different
      forms of darunavir can cause are of concern, and a more stable form is
      preferable. Important investigations of darunavir such as dissolution behavior,
      polymorphism, stability and degradation studies, and the impact of that on the
      quality of the product are being conducted by our working group. A cure for
      HIV/AIDS remains a long-term commitment, and there is much yet to achieve. This
      article discusses, by a critical review of the literature, the impact of the use
      of darunavir in the treatment of HIV-infected patients, its physical-chemical
      properties, the analytical methods to determine it, and challenges that remain in
      order to ensure the quality and stability of darunavir. 

PMID- 25391212
TI  - Methods for the chemical analysis of degradable synthetic polymeric biomaterials.
AB  - The performance of biodegradable polymeric systems strongly depends on their
      physical as well as on their chemical properties. Therefore, detailed chemical
      analysis of such systems is essential. Enzymatic and chemical hydrolysis are the
      primary biodegradation mechanisms for these materials. This review provides an
      overview of the strategies and analytical methods used for the structural and
      compositional chemical analysis of nondegraded, partially degraded, and fully
      degraded synthetic polymeric biomaterials with an emphasis on modern solution
      based techniques that yield large amounts of information. The degradation methods
      that facilitate the study of polymeric networks are also described. 

PMID- 25391213
TI  - Profiling serotonin reuptake inhibitors (SSRIs) in the environment: trends in
      analytical methodologies.
AB  - Selective serotonin reuptake inhibitor (SSRI) antidepressants are among the most
      prescribed pharmaceuticals worldwide and are ubiquitous in different areas of the
      environment. There are few reliable and specific analytical methods for the
      detection and quantification of SSRIs in environmental samples. The majority of
      the reported methods generally involve cleanup procedures that usually employ
      solid-phase extraction (SPE) followed by liquid chromatography with tandem mass
      spectrometry detection (LC-MS-MS). Herewith, a comprehensive overview of the
      described analytical methods available for the determination of SSRIs in
      environmental samples is provided. We address all steps involved in the
      analytical procedures, with the inherent advantages and disadvantages of each
      discussed. 

PMID- 25391214
TI  - HPLC-DAD determination of CNS-acting drugs in human blood, plasma, and serum.
AB  - This is a review of the literature regarding high-performance liquid
      chromatography-diode array detection (HPLC-DAD) procedures for the detection and
      determination of several categories of central nervous system-acting drugs in
      blood, plasma, or serum samples. Psychiatric and neurological drugs, such as
      antidepressants, benzodiazepines, antipsychotics, antiepileptics, and
      antiparkinsonians, have been included because of their relevance to therapeutic
      drug monitoring and systematic toxicological analysis. Articles published between
      2000 and January 2012 have been taken into consideration. This review has focused
      on methodological approaches, sample pretreatment techniques, and other practical
      aspects. 

PMID- 25391216
TI  - Concerns about latest NICE guidelines on acute heart failure.

PMID- 25391215
TI  - STC1 expression is associated with tumor growth and metastasis in breast cancer.
AB  - Stanniocalcin-1 (STC1) is a secreted glycoprotein implicated in several
      pathologies including retinal degeneration, cerebral ischemia, angiogenesis and
      inflammation. Aberrant STC1 expression has been reported in breast cancer but the
      significance of this is not clear. High levels of STC1 expression were found in
      the aggressive 4T1 murine mammary tumor cells and in the MDA-MB-231 human breast
      cancer line. To investigate its significance, stable clones with STC1 down
      regulation using shRNA were generated in both tumor models. The consequences of
      STC1 down-regulation on cell proliferation, chemotactic invasion, tumor growth
      and metastasis were assessed. Down-regulation of STC1 in the 4T1 murine mammary
      tumor cells had a major impact on mammary tumor growth. This observation was
      replicated in a second tumor model with the MDA-MB-231 human breast cancer line,
      with a significant reduction in primary tumor formation and a major inhibition of
      metastasis as well. Interestingly, in both models, proliferation in vitro was not
      affected. Subsequent microarray gene expression profiling identified 30 genes to
      be significantly altered by STC1 down-regulation, the majority of which are
      associated with known hallmarks of carcinogenesis. Furthermore, bioinformatic
      analysis of breast cancer datasets revealed that high expression of STC1 is
      associated with poor survival. This is the first study to show definitively that
      STC1 plays an oncogenic role in breast cancer, and indicates that STC1 could be a
      potential therapeutic target for treatment of breast cancer patients. 

PMID- 25391217
TI  - Studying disability trends in aging populations.
AB  - This article reviews the current literature on disability trends in aging
      populations and proposes a framework for studying disability trends built upon
      existing models of disablement. In addition to considering disablement and its
      associated factors, our framework also includes factors at population level and
      the interplays among personal resources and health behaviors, intervention
      programs, technological advances, and the consequences of disability trends in
      the context of life course and socio-ecological perspective. The framework is
      abbreviated FE-BRIT-SE to denote individual-level (F)ixed attributes, including
      genetic factors, personality, age, sex, and earlier life conditions, and the
      (E)nvironment; individual (B)ehaviors, (R)esources, (I)nterventions,
      (T)echnology; and (S)ocioeconomic and (E)cological consequences of disability
      trends. The overview offers an integrated framework for understanding the
      disablement process, trends and their complex milieu of causes and consequences. 

PMID- 25391218
TI  - Fighting for wellness: strategies of mid-to-older women living with cancer.
AB  - A significant portion of older adult cancer patients are using complementary and
      alternative medicine (CAM ) during and after treatment. I used four case studies
      to examine the strategies of older adult CAM-using cancer patients to maintain a
      sense of well-being as they transitioned to a post-treatment phase of life. Data
      were collected via qualitative interviews. Findings included strategies for
      financing CAM treatments, dealing with life disruption, and managing the complete
      nutritional overhaul recommended by their program. Participants worked to achieve
      new lifestyles and senses of wellness, finding ways to pay for expensive, out-of
      pocket care while still meeting family obligations. These findings shed light on
      assumptions about older adult health-seeking behaviors, culturally embedded life
      course expectations, and raised questions about how the pursuit of health
      activities involving boundary crossings are received. 

PMID- 25391219
TI  - "Grain for Green" driven land use change and carbon sequestration on the Loess
      Plateau, China.
AB  - Land-use change is widely considered to be a major factor affecting soil carbon
      (C) sequestration (DeltaCs). This paper studied changes to soil C stocks (Cs)
      following the conversion of farmland to forest, shrub and grassland across the
      key area for implementing China's "Grain for Green"--the Loess Plateau. The
      results are based on a synthesis of 44 recent publications (including 424
      observations at 70 sites) which has allowed us to further refine our
      understanding of the mechanisms driving the increase in Cs following farmland
      conversion. This synthesis suggests that the DeltaCs potential of the Loess
      Plateau could reach 0.59 Tg yr(-1) based on an estimated annual average DeltaCs
      rate of 0.29 Mg ha(-1) yr(-1). In the region's different rainfall zones both the
      main contributing factors and Cs dynamics varied. Across the entire Loess
      Plateau, Cs showed first an increasing (<5 yr) then a decreasing (6-10 yr)
      tendency only to increase (>10 yr) yet again. In addition, the DeltaCs rates
      depended primarily on restoration age. This synthesis demonstrates that both the
      initial s Cs and the average annual temperature have a significant effect on
      DeltaCs while the effect of land-use conversion type, rainfall zone, and average
      annual precipitation were minimal.

PMID- 25391220
TI  - In-situ one-step hydrothermal synthesis of a lead germanate-graphene composite as
      a novel anode material for lithium-ion batteries.
AB  - Lead germanate-graphene nanosheets (PbGeO3-GNS) composites have been prepared by
      an efficient one-step, in-situ hydrothermal method and were used as anode
      materials for Li-ion batteries (LIBs). The PbGeO3 nanowires, around 100-200 nm in
      diameter, are highly encapsulated in a graphene matrix. The lithiation and de
      lithiation reaction mechanisms of the PbGeO3 anode during the charge-discharge
      processes have been investigated by X-ray diffraction and electrochemical
      characterization. Compared with pure PbGeO3 anode, dramatic improvements in the
      electrochemical performance of the composite anodes have been obtained. In the
      voltage window of 0.01-1.50 V, the composite anode with 20 wt.% GNS delivers a
      discharge capacity of 607 mAh g(-1) at 100 mA g(-1) after 50 cycles. Even at a
      high current density of 1600 mA g(-1), a capacity of 406 mAh g(-1) can be
      achieved. Therefore, the PbGeO3-GNS composite can be considered as a potential
      anode material for lithium ion batteries.

PMID- 25391221
TI  - Development and preliminary evaluation of a novel low cost VR-based upper limb
      stroke rehabilitation platform using Wii technology.
AB  - PURPOSE: This paper proposes a novel system (using the Nintendo Wii remote) that
      offers customised, non-immersive, virtual reality-based, upper-limb stroke
      rehabilitation and reports on promising preliminary findings with stroke
      survivors. METHOD: The system novelty lies in the high accuracy of the full
      kinematic tracking of the upper limb movement in real-time, offering strong
      personal connection between the stroke survivor and a virtual character when
      executing therapist prescribed adjustable exercises/games. It allows the
      therapist to monitor patient performance and to individually calibrate the system
      in terms of range of movement, speed and duration. RESULTS: The system was tested
      for acceptability with three stroke survivors with differing levels of
      disability. Participants reported an overwhelming connection with the system and
      avatar. A two-week, single case study with a long-term stroke survivor showed
      positive changes in all four outcome measures employed, with the participant
      reporting better wrist control and greater functional use. Activities, which were
      deemed too challenging or too easy were associated with lower scores of
      enjoyment/motivation, highlighting the need for activities to be individually
      calibrated. CONCLUSIONS: Given the preliminary findings, it would be beneficial
      to extend the case study in terms of duration and participants and to conduct an
      acceptability and feasibility study with community dwelling survivors.
      Implications for Rehabilitation Low-cost, off-the-shelf game sensors, such as the
      Nintendo Wii remote, are acceptable by stroke survivors as an add-on to upper
      limb stroke rehabilitation but have to be bespoked to provide high-fidelity and
      real-time kinematic tracking of the arm movement. Providing therapists with real
      time and remote monitoring of the quality of the movement and not just the amount
      of practice, is imperative and most critical for getting a better understanding
      of each patient and administering the right amount and type of exercise. The
      ability to translate therapeutic arm movement into individually calibrated
      exercises and games, allows accommodation of the wide range of movement
      difficulties seen after stroke and the ability to adjust these activities (in
      terms of speed, range of movement and duration) will aid motivation and adherence
      - key issues in rehabilitation. With increasing pressures on resources and the
      move to more community-based rehabilitation, the proposed system has the
      potential for promoting the intensity of practice necessary for recovery in both
      community and acute settings.

PMID- 25391222
TI  - A comparative clinical study of various methods of caries removal in children.
AB  - AIM: The aim of the study was to compare the efficacy of caries removal, time
      taken and to evaluate the pain threshold experienced by children during various
      caries removal methods. METHODS: One hundred and twenty patients aged between 4
      and 14 years requiring dental restorations were selected. Caries removal was
      completed using an air-rotor, hand instruments, Carisolv and polymer burs. The
      efficacy, time taken and pain thresholds were evaluated during caries removal by
      Ericsson et al. scale, visual analogue scale and verbal pain scale, respectively.
      STATISTICAL ANALYSIS: Data was collected and statistically analysed using one-way
      analysis of variance followed by Post Hoc comparison by Bonferroni method. The
      skewed data was analysed amongst groups by applying Kruskal-Wallis test followed
      by probability adjustment by Mann-Whitney test. RESULT: These results indicated
      that the efficacy of caries removal was highest with air-rotor and was least by
      the hand instrument, whilst Carisolv(r) was least painful and the most time
      consuming method. CONCLUSIONS: Caries removal with polymer burs and Carisolv were
      found to be as effective in caries removal and could be considered as
      alternatives to painful procedures as air-rotor in management of caries
      especially in children.

PMID- 25391224
TI  - Why lifespans are more variable among blacks than among whites in the United
      States.
AB  - Lifespans are both shorter and more variable for blacks than for whites in the
      United States. Because their lifespans are more variable, there is greater
      inequality in length of life-and thus greater uncertainty about the future-among
      blacks. This study is the first to decompose the black-white difference in
      lifespan variability in America. Are lifespans more variable for blacks because
      they are more likely to die of causes that disproportionately strike the young
      and middle-aged, or because age at death varies more for blacks than for whites
      among those who succumb to the same cause? We find that it is primarily the
      latter. For almost all causes of death, age at death is more variable for blacks
      than it is for whites, especially among women. Although some youthful causes of
      death, such as homicide and HIV/AIDS, contribute to the black-white disparity in
      variance, those contributions are largely offset by the higher rates of suicide
      and drug poisoning deaths for whites. As a result, differences in the causes of
      death for blacks and whites account, on net, for only about one-eighth of the
      difference in lifespan variance. 

PMID- 25391225
TI  - Heterogeneity in expected longevities.
AB  - We develop a new methodology to compute differences in the expected longevity of
      individuals of a given cohort who are in different socioeconomic groups at a
      certain age. We address the two main problems associated with the standard use of
      life expectancy: (1) that people's socioeconomic characteristics change, and (2)
      that mortality has decreased over time. Our methodology uncovers substantial
      heterogeneity in expected longevities, yet much less heterogeneity than what
      arises from the naive application of life expectancy formulae. We decompose the
      longevity differences into differences in health at age 50, differences in the
      evolution of health with age, and differences in mortality conditional on health.
      Remarkably, education, wealth, and income are health-protecting but have very
      little impact on two-year mortality rates conditional on health. Married people
      and nonsmokers, however, benefit directly in their immediate mortality. Finally,
      we document an increasing time trend of the socioeconomic gradient of longevity
      in the period 1992-2008, and we predict an increase in the socioeconomic gradient
      of mortality rates for the coming years. 

PMID- 25391226
TI  - Supportive care needs of women with breast cancer in rural Scotland.
AB  - PURPOSE: The aim of this study was to identify the supportive care needs and
      unmet needs of women with breast cancer (BC) in rural Scotland. METHODS: In 2013,
      a survey of supportive care needs of rural women with BC was conducted using the
      short-form Supportive Care Needs Survey (SCNS-SF34). Semi-structured interviews
      were subsequently conducted with a purpose sample of questionnaire respondents.
      RESULTS: Forty-four women with BC completed the survey and ten were interviewed.
      Over half of participants reported at least one moderate to high unmet need (56.8
      %, n = 25), a tenth reported low needs (11.4 %, n = 5), and around a third
      reported no unmet needs for all 34 items (31.8 %, n = 14). The most prevalent
      moderate to high needs were 'being informed about cancer in remission' (31.8 %, n
      = 14), 'fears about the cancer spreading' (27.3 %, n = 12), 'being adequately
      informed about the benefits and side-effects of treatment' and 'concerns about
      the worries of those close to you' (both 25.0 %, n = 11). Interviews highlighted
      the following unmet needs: information about treatment and side effects, overview
      of care, fear of recurrence, impact on family and distance from support.
      CONCLUSIONS: Rural women with BC report similar unmet needs to their urban
      counterparts. Fear of recurrence is a key unmet need that should be addressed for
      all women with BC. However, they also report unique unmet needs because of rural
      location. Thus, it is critical that cancer services address the additional unmet
      needs of rural women with BC and, in particular, needs relating to distance from
      services.

PMID- 25391227
TI  - Congener-specific analysis of polychlorinated naphthalenes (PCNs) in the major
      Chinese technical PCB formulation from a stored Chinese electrical capacitor.
AB  - Impurity of polychlorinated naphthalenes (PCNs) in commercial polychlorinated
      biphenyl (PCB) formulations has been recognized as a relevant source of PCNs in
      the environment. Congener-specific analysis of most main PCB formulations has
      been accomplished previously, excluding the Chinese product. The insulating oil
      in a stored Chinese electric capacitor containing the major Chinese technical
      formulation "PCB3" was sampled and tested by isotope dilution technology using
      high-resolution gas chromatography coupled to high-resolution mass spectrometry
      (HRGC/HRMS). The detected concentration of PCNs in the Chinese PCB oil sample was
      1,307.5 MUg/g and therefore significantly higher than that reported in PCB
      formulations from other countries, as well as that in the transformer oil
      (ASKAREL Nr 1740) additionally tested in the present study for comparison. Based
      on the measurement, the total amount of PCNs in Chinese PCB3 oil is estimated to
      be 7.8 t, which would mean only 0.005 % of global production of PCNs of 150,000
      t. The homolog profile is similar to those of PCN in Aroclor 1262 and Clophen
      A40, where the contributions from hexa-CNs and hepta-CNs are predominant and
      accounted for similar proportions. The Toxic Equivalent Quantity (TEQ)
      concentration of dioxin-like PCN congeners is 0.47 MUg TEQ/g, with the dominant
      contributors of CN-73 and CN-66/67. This TEQ content from PCN is higher than that
      in most other PCB formulations with the exemption of the Russian Sovol
      formulation. The total TEQ in the historic 6,000 t of the Chinese PCB3
      formulation is estimated to be 2.8 kg TEQ.

PMID- 25391228
TI  - The change of organic matter in sewage sludge composting and its influence on the
      adsorption of pentachlorophenol (PCP).
AB  - Due to the abundance of organic matter in compost, the addition of compost to
      soil can promote the adsorption of pesticides. However, few studies have examined
      the influence of the composting duration on the organic matter (OM)
      transformation and adsorption capacity of the compost. In this study, a mixture
      of sewage sludge and straw was composted, and then the physicochemical properties
      of various OM were studied. Additionally, the sorption capacities of humic acid
      (HA), humin (HM), humic acid + humin, and fulvic acid (FA) + humic acid + humin
      extracted from composts of different stages toward pentachlorophenol (PCP) were
      compared. The sorption data can be well-described by the Freundlich model, and
      the sorption capacity of PCP on HM is the strongest of all organic components.
      After 120 days of composting, the sorption abilities of HA and HM increased by
      54.76 and 36.73%, respectively, which corresponds with increases in the
      aromatization degree, BET specific area, and pore volume and with a decrease in
      acid functional groups. The sorption ability of HA and HM increased by 54.76 and
      36.73% due to the increase of the aromatization degree. However, the sorption
      capacity of the compost decreased by 51.2%, which resulted from a decrease in
      total organic matter content and from the interaction between organic components
      in composts. This could be verified by the sequence of the sorption capacity: HM
      > HM + HA > HM + HA + FA > HA. The contribution of humus to the sorption of PCP
      onto compost is approximately 41 to 55%, and it increases with composting time.
      Therefore, it is possible that other components are present that affect the
      adsorption of PCP on composts.

PMID- 25391229
TI  - Fish embryo tests with Danio rerio as a tool to evaluate surface water and
      sediment quality in rivers influenced by wastewater treatment plants using
      different treatment technologies.
AB  - In order to evaluate surface water and the sediment quality of rivers connected
      to wastewater treatment plants (WWTPs) with different treatment technologies,
      fish embryo tests (FET) with Danio rerio were conducted using native water and
      sediment samples collected upstream and downstream of four WWTPs in Southern
      Germany. Two of these WWTPs are connected to the Schussen River, a tributary of
      Lake Constance, and use a sand filter with final water purification by
      flocculation. The two others are located on the rivers Schmiecha and Eyach in the
      area of the Swabian Alb and were equipped with a powdered activated carbon stage
      20 years ago, which was originally aimed at reducing the release of stains from
      the textile industry. Several endpoints of embryo toxicity including mortality,
      malformations, reduced hatching rate, and heart rate were investigated at defined
      time points of embryonic development. Higher embryotoxic potentials were found in
      water and sediments collected downstream of the WWTPs equipped with sand
      filtration than in the sample obtained downstream of both WWTPs upgraded with a
      powdered activated carbon stage. 

PMID- 25391230
TI  - Pharmaceuticals and consumer products in four wastewater treatment plants in
      urban and suburb areas of Shanghai.
AB  - Ten pharmaceuticals and two consumer products were investigated in four
      wastewater treatment plants (WWTPs) in Shanghai, China. The concentrations of
      target compounds in the wastewater influents ranged from below the limit of
      quantification (LOQ) to 9340 ng/L, with the frequency of detection of 31-100%,
      and the removal efficiencies were observed to be -82 to 100% in the four WWTPs.
      Concentrations of most target compounds (i.e. diclofenac, caffeine, metoprolol,
      sulpiride) in the wastewater influents were around three to eight times higher in
      urban WWTPs than in suburb ones, probably due to the different population served
      and lifestyles. Mean concentrations of target compounds in the wastewater
      influent generally decreased by 5-76% after rainfall due to the dilution of raw
      sewage by rainwater, which infiltrated into the sewer system. In the WWTPs
      located in the suburb area, the increased flow of wastewater influent led to a
      shortened hydraulic retention time (HRT) and decreased removal efficiencies of
      some compounds. On the contrary, the influence of rainfall was not significant on
      the removal efficiencies of investigated compounds in urban WWTPs, probably due
      to the almost unchanged influent flow, good removal performance, or bypass system
      employed.

PMID- 25391231
TI  - Perspective on polychlorinated dibenzo-p-dioxin and dibenzofuran emissions during
      chemical production in China: an overlooked source of contemporary relevance.
AB  - Polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDDs/DFs) are pollutants of
      significant global concern, and China with its large size and industries is one
      of the main dioxin-emitting countries in the world. PCDDs/DFs may be formed
      during the manufacture of chemicals and can either remain in the products as
      impurities or be emitted into the environment or residues disposed to landfills.
      The uncertainties in the environmental emissions of PCDDs/DFs from the chemical
      production industry in China are large because of the complex nature of the
      industry and variability in the technologies used and limited monitoring
      conducted. In the current study, we used the PCDD/DF emission factor from the
      updated United Nations Environment Programme (UNEP) toolkit 2013, information
      from otherwise published data, and the chemical production data in 2010 to
      estimate PCDD/DF emissions from the chemical productions in China. Based on these
      data, it was estimated that there is 1480 g toxic equivalent (TEQ) from the
      chemical production industry in China, which is much higher than the value that
      was estimated and used in the national implementation plans (NIPs) for China
      (102.4 g TEQ in 2004). These results indicate that current PCDD/DF emissions from
      the chemical production industry in China may be overlooked. Therefore, we
      suggest that attention should be paid to PCDD/DF emissions from the chemical
      production industry in future updates of the Chinese NIP and that appropriate
      measures to decrease PCDD/DF emissions should be taken by better monitoring of
      products and processes in chemical production industry.

PMID- 25391232
TI  - Impact of reference geosorbents on oral bioaccessibility of PAH in a human in
      vitro digestive tract model.
AB  - Former studies on human oral bioaccessibility of polycyclic aromatic hydrocarbons
      (PAH) from natural soil samples using human in vitro digestive tract models
      (physiologically based extraction tests, PBET) show highly variable results (0
      100% of mobilized PAH). Apart from other factors, the type and amount of present
      geosorbents are assumed to be significant for the degree of desorption/release of
      PAH into the digestive juice. Therefore, in this study, the reference geosorbents
      pure quartz sand, Na-montmorillonite clay, Pahokee peat, and charcoal "Sommerhit"
      were spiked with selected deuterated PAH and employed as single materials in a
      PBET. Lowest bioaccessibility was determined in charcoal, representing black
      carbon (0.1 +/- 0.1 % for ?10 PAH-d) in contrast to higher bioaccessibility in
      peat (6.4 +/- 2.2%) and clay (4.8 +/- 1.1%). Highest bioaccessibility was
      determined in sand (26.9 +/- 7.5%). The results show a systematic impact of
      heterogeneous geosorbents on human oral bioaccessibility of PAH and particularly
      black carbon acting as a very strong geosorbent that reduces human health risk.

PMID- 25391233
TI  - Changes in the abundance of sugars and sugar-like compounds in tall fescue
      (Festuca arundinacea) due to growth in naphthalene-treated sand.
AB  - The hydrophilic metabolome of tall fescue (Festuca arundinacea) adapted to grow
      in naphthalene-treated sand (0.8 g kg(-1) sand dw) was analysed using gas
      chromatography-mass spectrometry, and peaks corresponding to the more abundant
      compounds were tentatively identified from analysis of their mass spectral
      features and reference to the NIST Mass Spectral Database. Particular attention
      was paid to sugars as they are known to play important roles as stress regulators
      in plants. The results showed that the abundance of sugars was greater in the
      roots but lesser in the shoots of treated plants when compared to their control
      counterparts. The results for indole acetic acid (IAA) were notable: IAA was
      prominently less in the treated roots compared to shoots, and in treated shoots,
      IAA was particularly subdued compared to untreated shoots consistent with IAA
      degradation in treated plant tissues. The differences in the molecular phenotype
      between control and treated plants were expressed in root structural differences.
      The treated roots were modified to have greater suberisation, enhanced thickening
      in the endodermis and distortions in the cortical zone as demonstrated through
      scanning electron and epi-fluorescence microscopy.

PMID- 25391234
TI  - Comment on "Performance of ANFIS versus MLP-NN dissolved oxygen prediction models
      in water quality monitoring A. Najah & A. El-Shafie & O. A. Karim & Amr H. El
      Shafie. Environ Sci Pollut Res (2014) 21:1658-1670".

PMID- 25391236
TI  - Seasonal variation of Legionella in Taiwan's reservoir and its relationships with
      environmental factors.
AB  - In this study, the presence of Legionella in major water reservoirs of Taiwan was
      examined with respect to seasonal variation, geographical variation, and water
      quality parameters using TaqMan real-time qPCR. Water samples were collected
      quarterly at 19 reservoirs in Taiwan between November 2012 and August 2013. The
      detection rate for Legionella was 35.5% (27/76), and Legionella was detected in
      all seasons. The Legionella concentration was relatively high in spring and
      summer, reaching 3.86 * 10(8) and 7.35 * 10(8) cells/L, respectively. By sampling
      the area, Legionella was detected at a higher proportion in reservoirs in the
      northern and southern areas, and the difference was consistent in all seasons.
      Significant association was found between detection of Legionella and various
      water quality parameters, including conductivity, chlorophyll a, and dissolved
      oxygen (Mann-Whitney U test, P < 0.05). Results of Spearman rank test showed
      negative correlation for Legionella detection with pH (P = 0.030, R = -0.497) and
      dissolved oxygen (P = 0.007, R = -0.596) in fall and positive correlation with
      Carlson's trophic state index (P = 0.049, R = 0.457) in spring. The identified
      species included Legionella pneumophila and Legionella drancourtii. The detection
      of Legionella in reservoirs was indicative of a potential public health risk and
      should be further evaluated.

PMID- 25391235
TI  - Neighborhood epidemiological monitoring and adult mental health: European Quality
      of Life Survey, 2007-2012.
AB  - Little is monitored on perceived neighborhood noise, quality of drinking water,
      air quality, rubbish, traffic, etc. at a continental scale. This study was aimed
      to examine the relationships of such neighborhood risks and mental health in
      adults and the very old in an international and population-based setting across
      Europe. Data were retrieved from the European Quality of Life Survey, 2007-2012
      including demographics, living conditions, income and financial situation,
      housing and local environment, family, work, health, social participation and
      quality of social services. Adults aged 18 and above were included for
      statistical analysis (n = 79,270). Analysis included chi-square test, t test and
      logistic regression modeling. People who lived in town or city tended to indicate
      certain major problems for them such as noise (odds ratio (OR) 2.34, 95%
      confidence interval (CI) 2.17-2.53, P < 0.001), air quality (OR 2.76, 95% CI 2.54
      3.00, P < 0.001), low quality of drinking water (OR 1.33, 95% CI 1.23-1.43, P <
      0.001), crime and/or violence (OR 2.92, 95% CI 2.68-3.19, P < 0.001), rubbish (OR
      3.68, 95% CI 3.41-3.97, P < 0.001) and traffic congestion (OR 2.64, 95% CI 2.45
      2.85, P < 0.001). People who reported major problems on noise (OR 2.19, 95% CI
      1.96-2.45, P < 0.001), air quality (OR 2.11, 95% CI 1.87-2.37, P < 0.001), low
      quality of drinking water (OR 2.40, 95% CI 2.14-2.68, P < 0.001), crime and/or
      violence (OR 2.13, 95% CI 1.88-2.41, P < 0.001), rubbish (OR 1.98, 95% CI 1.77
      2.11, P < 0.001) and traffic congestion (OR 1.50, 95% CI 1.34-1.68, P < 0.001)
      were also classified as having depression. Perceived neighborhood conditions were
      associated with adult mental health across Europe. Future neighborhood monitoring
      research moving from the etiological to neighborhood management would be
      suggested.

PMID- 25391238
TI  - Erratum to: Two Streptomyces Species Producing Antibiotic, Antitumor, and Anti
      Inflammatory Compounds Are Widespread Among Intertidal Macroalgae and Deep-Sea
      Coral Reef Invertebrates from the Central Cantabrian Sea.

PMID- 25391237
TI  - Different continuous cropping spans significantly affect microbial community
      membership and structure in a vanilla-grown soil as revealed by deep
      pyrosequencing.
AB  - In the present study, soil bacterial and fungal communities across vanilla
      continuous cropping time-series fields were assessed through deep pyrosequencing
      of 16S ribosomal RNA (rRNA) genes and internal transcribed spacer (ITS) regions.
      The results demonstrated that the long-term monoculture of vanilla significantly
      altered soil microbial communities. Soil fungal diversity index increased with
      consecutive cropping years, whereas soil bacterial diversity was relatively
      stable. Bray-Curtis dissimilarity cluster and UniFrac-weighted principal
      coordinate analysis (PCoA) revealed that monoculture time was the major
      determinant for fungal community structure, but not for bacterial community
      structure. The relative abundances (RAs) of the Firmicutes, Actinobacteria,
      Bacteroidetes, and Basidiomycota phyla were depleted along the years of vanilla
      monoculture. Pearson correlations at the phyla level demonstrated that
      Actinobacteria, Armatimonadetes, Bacteroidetes, Verrucomicrobia, and Firmicutes
      had significant negative correlations with vanilla disease index (DI), while no
      significant correlation for fungal phyla was observed. In addition, the amount of
      the pathogen Fusarium oxysporum accumulated with increasing years and was
      significantly positively correlated with vanilla DI. By contrast, the abundance
      of beneficial bacteria, including Bradyrhizobium and Bacillus, significantly
      decreased over time. In sum, soil weakness and vanilla stem wilt disease after
      long-term continuous cropping can be attributed to the alteration of the soil
      microbial community membership and structure, i.e., the reduction of the
      beneficial microbes and the accumulation of the fungal pathogen. 

PMID- 25391239
TI  - Human embryos from overweight and obese women display phenotypic and metabolic
      abnormalities.
AB  - STUDY QUESTION: Is the developmental timing and metabolic regulation disrupted in
      embryos from overweight or obese women? SUMMARY ANSWER: Oocytes from overweight
      or obese women are smaller than those from women of healthy weight, yet post
      fertilization they reach the morula stage faster and, as blastocysts, show
      reduced glucose consumption and elevated endogenous triglyceride levels. WHAT IS
      KNOWN ALREADY: Female overweight and obesity is associated with infertility.
      Moreover, being overweight or obese around conception may have significant
      consequences for the unborn child, since there are widely acknowledged links
      between events occurring during early development and the incidence of a number
      of adult disorders. STUDY DESIGN, SIZE, DURATION: We have performed a
      retrospective, observational analysis of oocyte size and the subsequent
      developmental kinetics of 218 oocytes from 29 consecutive women attending for
      ICSI treatment and have related time to reach key developmental stages to
      maternal bodyweight. In addition, we have measured non-invasively the metabolic
      activity of 150 IVF/ICSI embryos from a further 29 consecutive women who donated
      their surplus embryos to research, and have related the data retrospectively to
      their body mass index (BMI). PARTICIPANTS/MATERIALS, SETTING, METHODS: In a
      clinical IVF setting, we compared oocyte morphology and developmental kinetics of
      supernumerary embryos collected from overweight and obese women, with a BMI in
      excess of 25 kg/m(2) to those from women of healthy weight. A Primovision Time
      Lapse system was used to measure developmental kinetics and the non-invasive
      COnsumption/RElese of glucose, pyruvate, amino acids and lactate were measured on
      spent droplets of culture medium. Total triglyceride levels within individual
      embryos were also determined. MAIN RESULTS AND THE ROLE OF CHANCE: Human oocytes
      from women presenting for fertility treatment with a BMI exceeding 25 kg/m(2) are
      smaller (R(2) = -0.45; P = 0.001) and therefore less likely to complete
      development post-fertilization (P < 0.001). Those embryos that do develop reach
      the morula stage faster than embryos from women of a BMI < 25 kg/m(2) (<0.001)
      and the resulting blastocysts contain fewer cells notably in the trophectoderm (P
      = 0.01). The resulting blastocysts also have reduced glucose consumption (R(2) = 
      0.61; P = 0.001), modified amino acid metabolism and increased levels of
      endogenous triglyceride (t = 4.11, P < 0.001). Our data further indicate that
      these differences are independent of male BMI. LIMITATIONS, REASONS FOR CAUTION:
      Although statistical power has been achieved, this is a retrospective study and
      relatively small due to the scarcity of human embryos available for research.
      Consequently, subanalysis of overweight and obese was not possible based on the
      sample size. The analysis has been performed on supernumerary embryos,
      originating from a single IVF unit and not selected for use in treatment. Thus,
      it was not possible to speculate how representative the findings would be of the
      better quality embryos transferred or frozen for each patient. WIDER IMPLICATIONS
      OF THE FINDINGS: The data indicate that a high BMI of women at conception is
      associated with distinct phenotypic changes in the embryo during the
      preimplantation period, highlighting the importance of prepregnancy body weight
      in optimizing the chances of fertility and safeguarding maternal and offspring
      health. These changes to the metabolic fingerprint of human embryos which are
      most likely a legacy of the ovarian conditions under which the oocyte has matured
      may reduce the chances of conception for overweight women and provide good
      evidence that the metabolic profile of the early embryo is set by sub-optimal
      conditions around the time of conception. The observed changes could indicate
      long-term implications for the health of the offspring of overweight and obese
      women. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Hull IVF
      Unit Charitable Trust and the Hull York Medical School. There are no conflict of
      interests.

PMID- 25391240
TI  - Effect of cytosine arabinoside metabolizing enzyme expression on drug toxicity in
      acute myeloid leukemia.

PMID- 25391242
TI  - "Current Biotechnological Approaches for Studying G Protein Coupled Receptor
      Structure, Function and Signaling"

PMID- 25391241
TI  - Foretinib is effective therapy for metastatic sonic hedgehog medulloblastoma.
AB  - Medulloblastoma is the most common malignant pediatric brain tumor, with
      metastases present at diagnosis conferring a poor prognosis. Mechanisms of
      dissemination are poorly understood and metastatic lesions are genetically
      divergent from the matched primary tumor. Effective and less toxic therapies that
      target both compartments have yet to be identified. Here, we report that the
      analysis of several large nonoverlapping cohorts of patients with medulloblastoma
      reveals MET kinase as a marker of sonic hedgehog (SHH)-driven medulloblastoma.
      Immunohistochemical analysis of phosphorylated, active MET kinase in an
      independent patient cohort confirmed its correlation with increased tumor relapse
      and poor survival, suggesting that patients with SHH medulloblastoma may benefit
      from MET-targeted therapy. In support of this hypothesis, we found that the
      approved MET inhibitor foretinib could suppress MET activation, decrease tumor
      cell proliferation, and induce apoptosis in SHH medulloblastomas in vitro and in
      vivo. Foretinib penetrated the blood-brain barrier and was effective in both the
      primary and metastatic tumor compartments. In established mouse xenograft or
      transgenic models of metastatic SHH medulloblastoma, foretinib administration
      reduced the growth of the primary tumor, decreased the incidence of metastases,
      and increased host survival. Taken together, our results provide a strong
      rationale to clinically evaluate foretinib as an effective therapy for patients
      with SHH-driven medulloblastoma.

PMID- 25391243
TI  - Oridonin, a promising antitumor natural product in the chemotherapy of
      hematological malignancies.
AB  - Oridonin, an ent-kaurane diterpenoid mainly extracted from Chinese medical plant
      Rabdosia rubescens and some related species, has been reported its remarkable
      antitumor efficacy in various cancer cells. This review will be focused on the
      underlying molecular mechanisms for the treatments of oridonin in hematological
      malignancies, which include the regulation of oncoproteins (AML1-ETO, NPM1
      mutants, PML-RARalpha, ABL kinase), accumulation of ROS, modulation of MAPKs and
      PI3K/Akt signaling pathways, and changes of abnormal expressions of MicroRNAs.
      And we get the conclusion that oridonin is a promising natural product with
      multiple targets against hematological malignancies. 

PMID- 25391244
TI  - Oil-based formulation as a sustained-released injection for a novel synthetic
      peptide.
AB  - In this study, sustained-release of GnRH antagonist peptide LXT-101 was realized
      through oil formulation, and their releasing characteristics in vitro and in vivo
      were investigated. In this formulation, the static interaction between cationic
      charged peptide LXT-101 and the negative charged phospholipid led to the
      formation of the phospholipid-peptide complex, by which LXT-101 was completely
      dissolved in oils. This formulation was prepared by mixing an aqueous solution of
      LXT-101 and empty SUV (small unilamellar liposomes) containing EPC
      (phosphatidylcholine) and DPPG (1, 2-dipalmitog-sn-glycero-3- phosphoglycerol) at
      an appropriate ratio, the mixture was subsequently lyophilized, and the resultant
      was dissolved in the oil to form a clear oily solution containing solubilized
      peptide LXT-101. With atomic force microscopy combined with Langmuir-Blodgett
      technology, the morphology of the particles in the oily solution were examined to
      be oval-shaped and the mean particle size was 150 nm in diameter. In pure water
      at 37 degrees C, about 70~90 % of LXT-101 was released slowly from the oily
      formulation over 7 days. An effective sustained suppression of testosterone in
      beagle dogs could be achieved over a period of seven days with this LXT-101 oily
      formulation, by i.m. at a dose of 0.2 mg/kg (2 mg/ml). This formulation
      dramatically improved the bioactivity of LXT-101 compared to its aqueous
      solution. It was also found that when the concentration of peptide LXT-101 was up
      to or over 10 mg/ml in aqueous solution, there was no significant difference
      between the oily formulation and aqueous solution. This fact meant that LXT-101
      itself could conduct sustained release in vivo by self-assembly of nanofibers. 

PMID- 25391245
TI  - Naringin inhibits TNF-alpha induced oxidative stress and inflammatory response in
      HUVECs via Nox4/NF-kappa B and PI3K/Akt pathways.
AB  - In the development of atherosclerosis, naringin has exhibited potential
      protective effects. However, the specific mechanisms are not clearly understood.
      The aim of this trial was to determine the anti-oxidative and anti-inflammatory
      effects of naringin and uncover the mechanisms in Tumor Necrosis Factor-alpha
      (TNF-alpha) induced Human Umbilical Vein Endothelial Cells (HUVECs). Reactive
      Oxygen Species (ROS) were measured by flow cytometry assay. The levels of NADPH
      oxidase 4 (Nox4), p22(phox), intercellular adhesion molecule-1 (ICAM-1) and
      vascular cell adhesion molecule-1 (VCAM-1) over-expressions were measured by qRT
      PCR and Western blotting analyses. Activation of Phosphatidylinositol 3
      kinase/Akt (PI3K/Akt) and Nuclear Factor-kappaB (NF-kappaB) was evaluated by
      Western blotting. Naringin inhibited ROS production as well as over-expression
      levels of Nox4, p22(phox) induced by TNF-alpha. Naringin inhibited TNF-alpha
      induced mRNA and protein over-expressions of ICAM-1 and VCAM-1. Naringin also
      suppressed activation of NF-kappaB and PI3K/Akt signaling pathways. These results
      indicated the preventive effects of naringin on HUVECs injury caused by oxidative
      stress and inflammation response and the effects might be obtained via inhibition
      of Nox4 and NF-kappaB pathways as well as activation of PI3K/Akt pathway.
      Naringin may be useful in preventing endothelial dysfunction, therefore to
      ameliorate the development of atherosclerosis. 

PMID- 25391246
TI  - Undercarboxylated osteocalcin may be an attractive marker of teriparatide
      treatment in rheumatoid arthritis patients.

PMID- 25391247
TI  - Low skeletal muscle mass associates with low femoral neck strength, especially in
      older Korean women: the Fourth Korea National Health and Nutrition Examination
      Survey (KNHANES IV).
AB  - SUMMARY: Data gathered from a nationally representative cohort demonstrated that
      subject with low skeletal muscle mass had consistently low femoral neck composite
      strength indices for compression, bending, and impact, especially in older women,
      supporting the highly integrated nature of skeletal muscle and bone.
      INTRODUCTION: Skeletal muscle and bone interact mechanically and functionally.
      The present study was performed to investigate the association between muscle
      mass and femoral neck composite strength indices using a nationally
      representative cohort. METHODS: This is a population-based, cross-sectional study
      from Korea National Health and Nutrition Examination Surveys, including 1,275
      Koreans (674 women and 601 men) aged 50 years or older. Femoral neck axis length
      and width were measured by hip DXA scans and were combined with BMD, body weight,
      and height to create composite indices of femoral neck strength relative to load
      in three different failure modes: compression, bending, and impact. Presarcopenia
      was defined as an appendicular skeletal muscle mass (ASM) divided by body weight
      that was less than 1 SD below the sex-specific mean for young adults. RESULTS:
      After adjusting for confounders, women with presarcopenia had consistently lower
      indices for compression strength (CSI), bending strength (BSI), and impact
      strength (ISI) than women without this condition. Men with presarcopenia had a
      lower ISI value than men without presarcopenia. Multiple regression analyses
      revealed that lower relative skeletal muscle mass (ASM/weight) associated
      significantly with lower values for all three femoral neck composite indices in
      women and with lower CSI and ISI in men. CONCLUSIONS: These findings provide the
      first clinical evidence for the notion that age-related low muscle mass may
      increase the risk of osteoporotic hip fractures by decreasing femoral neck
      strength relative to load, especially in older women, and support the highly
      integrated nature of skeletal muscle and bone.

PMID- 25391248
TI  - Calcium gluconate supplementation is effective to balance calcium homeostasis in
      patients with gastrectomy.
AB  - We demonstrate histological evidence for hyperparathyroidism in patients with
      gastrectomy. This is, at least in part, explained by impaired calcium absorption,
      resulting in mineralization defects and secondary hyperparathyroidism.
      Additionally, we demonstrate improved bone mineralization in patients with
      gastrectomy after gluconate therapy and showed the effectiveness of calcium
      gluconate over carbonate to balance impaired calcium hemostasis in mice.
      INTRODUCTION: Gastrectomy and hypochlorhydria due to long-term proton pump
      inhibitor therapy are associated with increased fracture risk because of
      intestinal calcium malabsorption. Hence, our objectives were to histologically
      investigate bone metabolism in patients with gastrectomy and to analyze the
      impact of calcium gluconate supplementation on skeletal integrity in the setting
      of impaired gastric acidification. METHODS: Undecalcified bone biopsies of 26
      gastrectomized individuals were histologically analyzed. In the clinical setting,
      we retrospectively identified 5 gastrectomized patients with sufficient vitamin D
      level, who were additionally supplemented with calcium gluconate and had a real
      bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria
      (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium
      carbonate supplementation on bone metabolism. RESULTS: Biopsies from
      gastrectomized individuals showed significantly increased osteoid, osteoclast,
      and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired
      calcium distribution in mineralized bone matrix compared to healthy controls.
      Five gastrectomized patients with sufficient vitamin D level demonstrated a
      significant increase in aBMD after a treatment with calcium gluconate alone for
      at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate
      in maintaining calcium metabolism in a mouse model of achlorhydria. CONCLUSION:
      Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired
      calcium distribution within the mineralized matrix. We show that calcium
      gluconate supplementation can increase bone mineral density in gastrectomized
      individuals and performs superior to calcium carbonate in restoring
      calcium/skeletal homoeostasis in a mouse model of achlorhydria.

PMID- 25391249
TI  - Interstitial lactate, lactate/pyruvate and glucose in rat muscle before, during
      and in the recovery from global hypoxia.
AB  - BACKGROUND: Hypoxia results in an imbalance between oxygen supply and oxygen
      consumption. This study utilized microdialysis to monitor changes in the energy
      related metabolites lactate, pyruvate and glucose in rat muscle before, during
      and after 30 minutes of transient global hypoxia. Hypoxia was induced in
      anaesthetised rats by reducing inspired oxygen to 6% O2 in nitrogen. RESULTS:
      Basal values for lactate, the lactate/pyruvate ratio and glucose were 0.72 +/-
      0.04 mmol/l, 10.03 +/- 1.16 and 3.55 +/- 0.19 mmol/l (n = 10), respectively.
      Significant increases in lactate and the lactate/pyruvate ratio were found in the
      muscle after the induction of hypoxia. Maximum values of 2.26 +/- 0.37 mmol/l for
      lactate were reached during early reperfusion, while the lactate/pyruvate ratio
      reached maximum values of 35.84 +/- 7.81 at the end of hypoxia. Following
      recovery to ventilation with air, extracellular lactate levels and the
      lactate/pyruvate ratio returned to control levels within 30-40 minutes.
      Extracellular glucose levels showed no significant difference between hypoxia and
      control experiments. CONCLUSIONS: In our study, the complete post-hypoxic
      recovery of metabolite levels suggests that metabolic enzymes of the skeletal
      muscle and their related cellular components may be able to tolerate severe
      hypoxic periods without prolonged damage. The consumption of glucose in the
      muscle in relation to its delivery seems to be unaffected.

PMID- 25391250
TI  - Peroxisome proliferator-activated receptor gamma inhibits pulmonary hypertension
      targeting store-operated calcium entry.
AB  - In this study, we investigated the role of peroxisome proliferator-activated
      receptor gamma (PPARgamma) on store-operated calcium entry (SOCE) and expression
      of the main store-operated calcium channel (SOCCs) components, canonical
      transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary
      hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and
      adenoviral overexpression strategies were constructed for loss-of-function and
      gain-of-function experiments. PPARgamma agonist rosiglitazone attenuates the
      pathogenesis of CHPH and suppresses Hif-1alpha, TRPC1, TRPC6 expression in the
      distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary
      arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and
      overexpression studies, and bioinformatical analysis of the TRPC gene promoter
      and luciferase reporter assay, we demonstrated that PPARgamma exerts roles of
      anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by
      inhibiting the elevated SOCE and TRPC expression. These effects were inhibited
      under the conditions of hypoxia or Hif-1alpha accumulation. We also found that
      under hypoxia, accumulated Hif-1alpha protein acts as upstream of suppressed
      PPARgamma level; however, targeted PPARgamma rescue acts as negative feedback on
      suppressing Hif-1alpha level and Hif-1alpha mediated signaling pathway. PPARgamma
      inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1alpha expression and
      signaling transduction. KEY MESSAGES: Rosiglitazone protects PH by normalizing
      RVSP but not right ventricle hypotrophy. PPARgamma inhibits PASMCs proliferation
      via targeting SOCE and TRPC by suppressing Hif-1alpha. PPARgamma and Hif-1alpha
      share mutual inhibitory regulation in PASMCs. PPARgamma restoration might be a
      beneficial strategy for PH treatment.

PMID- 25391252
TI  - Effects of Pycnogenol(r) on endothelial dysfunction in borderline hypertensive,
      hyperlipidemic, and hyperglycemic individuals: the borderline study.
AB  - AIM: This registry study aimed to evaluate the effects of supplementation with
      pycnogenol on altered endothelial function (EF) in borderline hypertensive,
      hyperlipidemic and hyperglycemic subjects without atherosclerotic changes in
      their main arteries and no coronary artery disease. METHODS: Flow mediated
      dilatation (FMD) and endothelium-independent (EID) dilatation were measured with
      brachial ultrasound after occlusion. Also, after occlusion, laser Doppler (LDF)
      flux and distal straingauge flow were measured. Oxidative stress (oxstress) was
      evaluated at 8 and 12 weeks. 93 subjects with borderline symptoms were enrolled
      into the study: 32 hypertensives, 31 hyperlipidemics, 30 hyperglycemics. All
      participants were instructed to follow the best available management to control
      their symptoms. In addition to best management, half of the subjects in each
      group used 150 mg/day Pycnogenol((r)). 31 normal subjects were included as
      control. RESULTS: After 12 weeks metabolic values and blood pressure were back to
      normal in all subjects. Values were slightly better under Pycnogenol((r)). FMD
      increased after 8 weeks from an average 5.3;3.4% to 8.2;2.2% with a further
      increase to 8.8;3.1% (P<0.05) at 12 weeks. No effects were found in controls and
      normal subjects. EID of normal subjects was consistently higher with 26%. LDF
      skin flux increased with Pycnogenol((r)) at 8 weeks and 12 weeks. The final flux
      increase was not different from normal values. In controls flux after occlusion
      was not improved at 8 weeks; there was a significant but minor increase at 12
      weeks. Flux increases were superior in all Pycnogenol((r)) subjects. In
      Pycnogenol((r)) subjects, limb flow after occlusion increased at 8 weeks with a
      further increase at 12 weeks. In controls inclusion flow after occlusion was
      comparable at 8 and 12 weeks. Oxidative stress was significantly decreased in
      Pycnogenol((r)) subjects at 8 and 12 weeks. Minor differences were observed in
      controls. CONCLUSION: This open registry study indicates that Pycnogenol((r))
      improves EF in preclinical, borderline subjects in a macro-microcirculatory
      model. This observation may suggest an important preventive possibility for
      borderline hypertensive, hyperglycemic and hyperlipidemic subjects.

PMID- 25391251
TI  - Bitter and sweet taste receptors in the respiratory epithelium in health and
      disease.
AB  - Taste receptors on the tongue communicate information to the brain about the
      nutrient content or potential toxicity of ingested foods. However, recent
      research has now shown that taste receptors are also expressed far beyond the
      tongue, from the airway and gastrointestinal epithelia to the pancreas and brain.
      The functions of many of these so-called extraoral taste receptors remain
      unknown, but emerging basic science and clinical evidence suggests that bitter
      and sweet taste receptors in the airway are important in sensing bacteria and
      regulating innate immunity. This review focuses on the role of bitter and sweet
      taste receptors in human airway innate immunity and the potential clinical
      relevance to airway infections. The T2R38 bitter taste receptor in sinonasal
      cilia detects bitter bacterial quorum-sensing molecules and activates nitric
      oxide-dependent innate immune responses. Polymorphisms that underlie T2R38
      functionality also appear to be involved in susceptibility to upper respiratory
      infection and chronic rhinosinusitis (CRS). Bitter and sweet receptors in
      specialized sinonasal solitary chemosensory cells control antimicrobial peptide
      secretion, which may have important implications for airway infections in CRS
      patients as well as patients with diabetes mellitus. Future research on taste
      receptors in the airway has tremendous potential to identify immune mechanisms
      involved in host-pathogen interactions and thus reveal novel therapeutic targets.

PMID- 25391253
TI  - The therapeutic potential of novel anti-migraine acute therapies.
AB  - INTRODUCTION: Migraine is a highly disabling neurovascular disorder. 'The complex
      and multifactorial properties of migraine pathogenesis provide the opportunity to
      identify new therapeutic targets from a wide range of receptors. AREAS COVERED:
      In this editorial, the authors focus on future pharmacological interventions for
      acute migraine including: 5-HT receptors and their agonists, calcitonin gene
      related peptide receptors and their antagonists, PAC1 receptors and their
      antagonists, glutamate receptors and some of their antagonists as well as
      transient receptor potential channels and their antagonists. The authors also
      discuss preventative treatments for migraine that are currently in development.
      EXPERT OPINION: Future pharmaceutical research that looks at the well-known
      mechanisms involved in the pathophysiology of migraine should aim to overcome the
      existing limitations of each pharmacological class and their side effects. There
      has lately been particular interest in the role of glutamate receptors,
      particularly metabotropic glutamate receptors, in the pathophysiology of
      migraine. These receptors may be potentially viable drug targets for migraine in
      the future.

PMID- 25391254
TI  - Ictal asystole and ictal syncope: insights into clinical management.
AB  - BACKGROUND: Ictal asystole is a rare, serious, and often treatable cause of
      syncope. There are currently limited data to guide management. Characterization
      of ictal syncope predictors may aid in the selection of high-risk patients for
      treatments such as pacemakers. METHODS AND RESULTS: We searched our epilepsy
      monitoring unit database from October 2003 to July 2013 for all patients with
      ictal asystole events. Clinical, electroencephalogram, and ECG data for each of
      their seizures were examined for their relationships with ictal syncope events.
      In 10 patients with ictal asystole, we observed 76 clinical seizures with 26
      ictal asystole episodes, 15 of which led to syncope. No seizure with asystole
      duration<=6 s led to syncope, whereas 94% (15/16) of seizures with asystole
      duration>6 s led to syncope (P=0.02). During ictal asystole events, 4 patients
      had left temporal seizure onset, 4 patients had right temporal seizure onset, and
      2 patients had both. Syncope was more common with left temporal (40%) than with
      right temporal seizures (10%; P=0.002). Treatment options included antiepileptic
      drug changes, epilepsy surgery, and pacemaker implantation. Eight patients
      received pacemakers. During follow-up of 72+/-95 months, all patients remained
      syncope free. CONCLUSIONS: Ictal asystole>6 s is strongly associated with ictal
      syncope. Ictal syncope is more common in left than in right temporal seizures. A
      permanent pacemaker should be considered in patients with ictal syncope if they
      are not considered good candidates for epilepsy surgery.

PMID- 25391255
TI  - Severity of Type 2 Diabetes, Cognitive Function, and Self-Care.
AB  - Type 2 diabetes mellitus (T2DM) is associated with poorer performance on certain
      measures of cognitive function. However, little is known about the associations
      among working memory (WM), executive function (EF), and self-care in those with
      severe T2DM. This investigation explored these relationships among 67 middle-aged
      and older individuals with T2DM (mean age of 62.9 years). Severity of T2DM was
      measured with a health status composite (HSC) score from the Diabetes Care
      Profile, the number of prescribed medications, and the number of comorbid
      conditions. Cognitive assessments included the Working Memory Index and the
      Executive Interview 25 (EXIT 25). Self-care was measured using the Self-Care
      Inventory-Revised (SCI-R) and hemoglobin A1c (HgbA1c). WM was significantly
      correlated with all measures of severity of T2DM (HSC, r = .542, p < . 01; number
      of comorbidities, r = -.476, p < .01; and number of prescription medications, r =
      -.344, p < .01). EF was significantly correlated with all measures of severity of
      T2DM (HSC, r = -.504, p < .01; number of comorbidities, r = .492, p < .01; and
      number of prescription medications, r = .326, p < .01). The self-care measure
      HgbA1c was significantly correlated with WM (r = -.352, p < .01) and EF (r =
      .510, p < .01). The EXIT 25 score fully mediated the relationship between
      severity of T2DM and self-care as measured by HgbA1c (beta = .431, p < .001).
      These findings provide preliminary evidence for the associations among severity
      of T2DM, WM, EF, and self-care. 

PMID- 25391256
TI  - Negative effect of aging on psychosocial functioning of adults with congenital
      heart disease.
AB  - BACKGROUND: Improvements in life expectancy among adults with congenital heart
      disease (ACHD) provide them with unique challenges throughout their lives and age
      related psychosocial tasks in this group might differ from those of healthy
      counterparts. This study aimed to clarify age-related differences in psychosocial
      functioning in ACHD patients and determine the factors influencing anxiety and
      depression. METHODS AND RESULTS: A total of 133 ACHD patients (aged 20-46) and
      117 reference participants (aged 20-43) were divided in 2 age groups (20 s and 30
      s/40 s) and completed the Hospital Anxiety and Depression Scale, Independent
      Consciousness Scale, and Problem-Solving Inventory. Only ACHD patients completed
      an illness perception inventory. ACHD patients over 30 showed a significantly
      greater percentage of probable anxiety cases than those in their 20 s and the
      reference group. Moreover, ACHD patients over 30 who had lower dependence on
      parents and friends, registered higher independence and problem-solving ability
      than those in their 20 s, whereas this element did not vary with age in the
      reference participants. Furthermore, ACHD patients may develop an increasingly
      negative perception of their illness as they age. The factors influencing anxiety
      and depression in patients were aging, independence, problem-solving ability, and
      NYHA functional class. CONCLUSIONS: Although healthy people are psychosocially
      stable after their 20 s, ACHD patients experience major differences and face
      unique challenges even after entering adulthood.

PMID- 25391257
TI  - Elevated fasting insulin level significantly increases the risk of
      microalbuminuria.
AB  - BACKGROUND: Microalbuminuria is significantly associated with long-term prognosis
      in the general population as well as in diabetic patients. It is well known that
      insulin resistance (IR) can induce microalbuminuria, but an elevated fasting
      insulin level, which is an early clinical manifestation of IR, as a risk factor
      for microalbuminuria has not been clarified, so we investigated the association
      between fasting insulin level and the development of microalbuminuria in a
      general population. METHODS AND RESULTS: A total of 1,192 non-diabetic Korean men
      without microalbuminuria in 2005 were followed until 2010. They were categorized
      into 3 groups according to their fasting insulin levels and monitored for the
      development of microalbuminuria. The incidence of microalbuminuria was compared
      among groups, and Cox proportional hazards models were used to calculate the
      hazard ratios for microalbuminuria according to the fasting insulin levels.
      During 4,013.0 person-years of follow-up, 51 incident cases of microalbuminuria
      developed between 2006 and 2010. The incidence of microalbuminuria increased in
      proportion to the fasting insulin levels (tertile 1: 1.8%, tertile 2: 4.5%,
      tertile 3: 6.5%, P<0.001). Hazard ratios for microalbuminuria also increased in
      proportion to the fasting insulin levels [tertile 1: reference, tertile 2: 2.44
      (1.01-5.89), tertile 3: 3.30 (1.40-7.78), respectively, P for trend 0.013].
      CONCLUSIONS: Elevated fasting insulin level was associated with the future
      development of microalbuminuria.

PMID- 25391258
TI  - Characteristics of intra-left atrial flow dynamics and factors affecting
      formation of the vortex flow - analysis with phase-resolved 3-dimensional cine
      phase contrast magnetic resonance imaging.
AB  - BACKGROUND: The intra-left atrial (LA) blood flow from pulmonary veins (PVs) to
      the left ventricle (LV) changes under various conditions and might affect global
      cardiac function. By using phase-resolved 3-dimensional cine phase contrast
      magnetic resonance imaging (4D-Flow), the intra-LA vortex formation was
      visualized and the factors affecting the intra-LA flow dynamics were examined.
      METHODS AND RESULTS: Thirty-two patients with or without organic heart diseases
      underwent 4D-Flow and transthoracic echocardiography. The intra-LA velocity
      vectors from each PV were post-processed to delineate streamline and pathline
      images. The vector images revealed intra-LA vortex formation in 20 of 32
      patients. All the vortices developed during the late systolic and early diastolic
      phases and were directed counter-clockwise when viewed from the subjects' cranial
      side. The flow vectors from the right PVs lengthened predominantly toward the
      mitral valves and partly toward the LA appendage, whereas those from the left PVs
      directed rightward along the posterior wall and joined the vortex. Patients with
      vortex had less organic heart diseases, smaller LV and LA volume, and greater
      peak flow velocity and volume mainly in the left PVs, although the flow
      directions from each PV or PV areas did not differ. CONCLUSIONS: 4D-Flow can
      clearly visualize the intra-LA vortex formation and analyze its characteristic
      features. The vortex formation might depend on LV and LA volume and on flow
      velocity and volume from PVs.

PMID- 25391259
TI  - Predictors of high defibrillation threshold in patients with implantable
      cardioverter-defibillator using a transvenous dual-coil lead.
AB  - BACKGROUND: Defibrillation testing (DT) is considered a standard procedure during
      implantable cardioverter-defibrillator (ICD) implantation. However, little is
      known about the factors that are significantly related to patients with high
      defibrillation threshold (DFT) using the present triad system. METHODS AND
      RESULTS: We examined 286 consecutive patients who underwent ICD implantation with
      a transvenous dual-coil lead and DT from December 2000 to December 2011. We
      defined patients who required 25 J or more by the implanted device as the high
      DFT group, and those who required less than 25 J as the normal DFT group. For
      each patient, assessment parameters included underlying disease, comorbidities,
      NYHA functional class, drugs, and echocardiographic measures. The high DFT group
      consisted of 12 patients (4.2%). Multivariate analysis identified 3 independent
      predictors for high DFT: atrial fibrillation (odds ratio (OR) 4.85, 95%
      confidence interval (CI) 1.24-22.33, P=0.023), hypertension (OR 4.01, 95% CI 1.08
      15.96, P=0.039), thickness of interventricular septum (IVS) >12 mm (OR 4.82, 95%
      CI 1.17-20.31, P=0.030). CONCLUSIONS: Atrial fibrillation, hypertension and IVS
      hypertrophy were significantly associated with high DFT. Identification of such
      patients could help to lower the risk of complications with DT.

PMID- 25391261
TI  - Change in model for end-stage liver disease score at two weeks, as an indicator
      of mortality or liver transplantation at 60 days in acute-on-chronic liver
      failure.
AB  - BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterised by a sudden
      deterioration of underlying chronic liver disease, resulting in increased rates
      of mortality and liver transplantation. Early prognostication can benefit optimal
      allocation of resources. METHODS: ACLF was defined as per the disease criteria of
      the Asian Pacific Association for the Study of the Liver. Inpatient discharge
      summaries from between January 2001 and April 2013 were reviewed. The primary
      outcome was mortality or liver transplantation within 60 days from onset of ACLF.
      Absolute 'model for end-stage liver disease' (MELD) score and change in MELD at
      Weeks 1, 2 and 4 were reviewed in order to identify the earliest point for
      prediction of mortality or liver transplantation. RESULTS: Clinical data were
      collected on 53 subjects who fulfilled the inclusion and exclusion criteria. At
      60 days from presentation, 20 patients (37.7%) died and 4 (7.5%) underwent liver
      transplantation. Increased MELD of >=2 after 2 weeks was 75.0% sensitive and
      75.9% specific for predicting mortality or liver transplantation. If the MELD
      score did not increase at 2 weeks, predictive chance of survival was 93.8% over
      the next 60 days. MELD change at 1 week showed poor sensitivity and specificity.
      Change at 4 weeks was too late for intervention. CONCLUSION: Change in MELD score
      at 2 weeks provides an early opportunity for prognostication in ACLF. A MELD
      score that does not deteriorate by Week 2 would predict 93.8% chance of survival
      for the next 60 days. This finding warrants further validation in larger cohort
      studies.

PMID- 25391262
TI  - Comparison of the structure of floral nectaries in two Euonymus L. species
      (Celastraceae).
AB  - The inconspicuous Euonymus L. flowers are equipped with open receptacular floral
      nectaries forming a quadrilateral green disc around the base of the superior
      ovary. The morphology and anatomy of the nectaries in Euonymus fortunei (Turcz.)
      Hand.-Mazz. and Euonymus europaeus L. flowers were analysed under a bright-field
      light microscope as well as stereoscopic and scanning electron microscopes.
      Photosynthetic nectaries devoid of the vascular tissue were found in both
      species. Nectar was exuded through typical nectarostomata (E. fortunei) or
      nectarostomata and secretory cell cuticle (E. europaeus). The nectaries of the
      examined species differed in their width and height, number of layers and
      thickness of secretory parenchyma, and the height of epidermal cells. Moreover,
      there were differences in the location and abundance of nectarostomata and the
      content of starch and phenolic compounds.

PMID- 25391263
TI  - Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a
      prospective randomized phase III study.
AB  - BACKGROUND: The current treatment of ovarian cancer consists of cytoreductive
      surgery (CRS) and systemic chemotherapy. The aim of this study was to examine if
      hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality to
      treat this category of patients along with a second attempt of surgical resection
      and second- or third-line systemic chemotherapy afterward. METHODS: In an 8-year
      period (2006-2013), 120 women with advanced ovarian cancer (International
      Federation of Gynecology and Obstetrics [FIGO] IIIc and IV) who experienced
      disease recurrence after initial treatment with conservative or debulking surgery
      and systemic chemotherapy were randomized into two groups. Group A comprised 60
      patients treated with CRS followed by HIPEC and then systemic chemotherapy. Group
      B comprised 60 patients treated with CRS only and systemic chemotherapy. RESULTS:
      The mean survival for group A was 26.7 versus 13.4 months in group B (p < 0.006).
      Three-year survival was 75 % for group A versus 18 % for group B (p < 0.01). In
      the HIPEC group, the mean survival was not different between patients with
      platinum-resistant disease versus platinum-sensitive disease (26.6 vs. 26.8
      months). On the other hand, in the non-HIPEC group, there was a statistically
      significant difference between platinum-sensitive versus platinum-resistant
      disease (15.2 vs. 10.2 months, p < 0.002). Complete cytoreduction was associated
      with longer survival. Patients with a peritoneal cancer index score of <15
      appeared also to have longer survival. CONCLUSIONS: The use of HIPEC along with
      the extent of the disease and the extent of cytoreduction play an important role
      in the survival of patients with recurrence in an initially advanced ovarian
      cancer.

PMID- 25391264
TI  - Contribution of Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Women with
      Early Stage Endometrial Cancer: Results of the SENTI-ENDO Study.
AB  - BACKGROUND: This study was designed to evaluate detection rate and anatomical
      location of sentinel lymph node (SLN) at lymphoscintigraphy, to compare short and
      long lymphoscintigraphy protocols, and to correlate lymphoscintigraphic and
      surgical mapping of SLN in patients with early-stage endometrial cancer (EC).
      METHODS: Subanalysis of the prospective multicenter study Senti-endo performed
      from July 2007 to August 2009. Patients with stage I and II EC received four
      cervical injections of 0-2 mL of unfiltered technetium sulphur colloid the day
      before (long protocol) or the morning (short protocol) before surgery. SLN
      detection used a combined technetium/patent blue labeling technique, and all
      patients had a systematic bilateral pelvic lymphadenectomy. RESULTS: A total of
      133 patients were enrolled in the study and 118 (94.5 %) underwent a
      lymphoscintigraphy. Of these 118 patients, 44 (37 %) underwent a short protocol
      and 66 (56 %) a long protocol (data on lymphoscintigraphy were not available in
      eight patients). Lymphoscintigraphic detection rate was 74.6 % (34 % for short
      protocol and 60.2 % for long protocol). No difference in the detection rate was
      observed according to lymphoscintigraphy protocol (p = 0.22), but a higher number
      of SLN was noted for the long protocol (p = 0.02). Aberrant drainage was noted on
      lymphoscintigraphy in 30.5 % of the patients. Paraaortic SLNs were exclusively
      detected using the long protocol. A poor correlation was noted between short
      (kappa test = 0.24) or long lymphoscintigraphy (kappa test = 0.3) protocol and
      SLN surgical mapping. CONCLUSIONS: Our study demonstrates that preoperative
      lymphoscintigraphy allowed a high SLN detection rate and that long
      lymphoscintigraphy protocol was associated with a higher detection of aberrant
      drainage especially in the paraaortic area.

PMID- 25391265
TI  - Erythropoietin-Producing Hepatocellular A1 is an Independent Prognostic Factor
      for Gastric Cancer.
AB  - BACKGROUND: Erythropoietin-producing hepatocellular (Eph) receptors are the
      largest subfamily of receptor tyrosine kinases that have been investigated as a
      possible target for molecular targeted therapy of various cancers. METHODS:
      Patients (n = 222) who underwent gastrectomy for primary gastric cancer were
      enrolled in this study. Tumor protein expression of EphA1 and EphB6 in surgically
      resected specimen was investigated using immunohistochemistry. The associations
      between expression of EphA1 and EphB6 and clinicopathological factors and
      prognosis were analyzed. RESULTS: High expression of EphA1 was associated with
      undifferentiated histology (P = 0.002), depth of tumor (P < 0.001), lymph node
      metastasis (P = 0.001), venous invasion (P = 0.015), stage (P = 0.001), and
      remote metastasis or recurrence (P < 0.001). In univariate analysis, patients
      with high expression of EphA1 had significantly poorer overall survival and
      relapse-free survival compared with patients with low EphA1 expression. The
      expression level of EphB6 was not associated with any clinicopathological factors
      and patient survival. Multivariate analysis indicated that depth of tumor [hazard
      ratio (HR) 9.26, 95 % confidence interval (CI) 0.03-0.46, P = 0.003], lymph node
      metastasis (HR 9.26, 95 % CI 0.07-0.39, P < 0.001), and high expression of EphA1
      (HR 1.86, 95 % CI 0.29-0.99, P = 0.048) are independent prognostic factors for
      relapse-free survival. CONCLUSIONS: EphA1 is a possible target of molecular
      targeted therapy of gastric cancer.

PMID- 25391266
TI  - Elevated Expression of N-Acetylgalactosaminyltransferase 10 Predicts Poor
      Survival and Early Recurrence of Patients with Clear-Cell Renal Cell Carcinoma.
AB  - PURPOSE: The aim of this study was to evaluate the potential prognostic
      significance of N-acetylgalactosaminyltransferase 10 (GALNT10) in patients with
      clear-cell renal cell carcinoma (ccRCC) after surgical resection. METHODS: We
      retrospectively enrolled 271 patients (202 in the training cohort and 69 in the
      validation cohort) with ccRCC undergoing nephrectomy at a single institution.
      Clinicopathologic features, overall survival (OS), and recurrence-free survival
      (RFS) were recorded. GALNT10 intensities were assessed by immunohistochemistry in
      the specimens of patients. The Kaplan-Meier method was applied to compare
      survival curves. Cox regression models were used to analyze the impact of
      prognostic factors on OS and RFS. Concordance index (C-index) was calculated to
      assess predictive accuracy. RESULTS: In both cohorts, elevated GALNT10 expression
      in tumor tissues positively correlated with advanced TNM stage. High GALNT10
      expression indicated poor survival and early recurrence of patients with ccRCC,
      particularly with early-stage disease. After backward elimination, GALNT10
      expression was identified as an independent adverse prognostic factor for
      survival and recurrence. The predictive accuracy of TNM, University of California
      Los Angeles Integrated Staging System, and stage, size, grade, and necrosis
      prognostic models was improved when GALNT10 expression was added. CONCLUSIONS:
      GALNT10 expression is a potential independent adverse prognostic biomarker for
      recurrence and survival of patients with ccRCC after nephrectomy.

PMID- 25391267
TI  - Immunoreactivity of lactic acid-treated mare's milk after simulated digestion.
AB  - The similarity of mare's milk to breast milk makes it an interesting substrate
      for the creation of dairy beverages. The aim of this study was to determine the
      immunoreactivity of the digested mare's milk products carried out by lactic acid
      fermentation with Lactobacillus casei LCY, Streptococcus thermophilus MK10 and
      Bifidobacterium animalis Bi30. Simulation of digestion with saliva, pepsin and
      pancreatin/bile salts was carried out. The immunoreactivity of the milk proteins
      was assessed by competitive ELISA. The separation of proteins was studied using a
      tricine SDS-PAGE method. It has been demonstrated that lactic acid fermentation
      significantly decreases the immunoreactivity of beta-lactoglobulin, beta-casein,
      kappa-casein and bovine serum albumin. The level of reduction was connected to
      the type of bacterial strain. The simulated digestion processes caused the
      decline of immunoreactivity, and the decreases obtained in the experiment were as
      follows: lactoferrin: 95%, beta-lactoglobulin: 94%, beta-casein: 93%, alpha
      lactalbumin: 82%, alpha-casein: 82%, bovine serum albumin: 76% and kappa-casein:
      37%. The results of the study indicated that microbial fermentation with tested
      strains is a valuable method for reducing the immunoreactivity of mare's milk
      proteins. However, further studies with other bacterial strains are needed to
      gain a higher level of elimination or total reduction of mare's milk
      immunoreactivity to possibly introduce fermented mare's milk into the diet of
      patients with immune-mediated digestive problems. 

PMID- 25391268
TI  - Ostwald's rule of stages governs structural transitions and morphology of
      dipeptide supramolecular polymers.
AB  - The self-assembly of molecular building blocks into nano- and micro-scale
      supramolecular architectures has opened up new frontiers in polymer science. Such
      supramolecular species not only possess a rich set of dynamic features as a
      consequence of the non-covalent nature of their core interactions, but also
      afford unique structural characteristics. Although much is now known about the
      manner in which such structures adopt their morphologies and size distributions
      in response to external stimuli, the kinetic and thermodynamic driving forces
      that lead to their transformation from soluble monomeric species into ordered
      supramolecular entities have remained elusive. Here we focus on Boc
      diphenylalanine, an archetypical example of a peptide with a high propensity
      towards supramolecular self-organization, and describe the pathway through which
      it forms a range of nano-assemblies with different structural characteristics.
      Our results reveal that the nucleation process is multi-step in nature and
      proceeds by Ostwald's step rule through which coalescence of soluble monomers
      leads to the formation of nanospheres, which then undergo ripening and structural
      conversions to form the final supramolecular assemblies. We characterize the
      structures and thermodynamics of the different phases involved in this process
      and reveal the intricate nature of the transitions that can occur between
      discrete structural states of this class of supramolecular polymers. 

PMID- 25391269
TI  - Seismic reflection data support episodic and simultaneous growth of the Tibetan
      Plateau since 25 Myr.
AB  - The spectacular topography of the Tibetan Plateau is the result of collision
      between India and Eurasia over some 50 Myr, but how the plateau grew to its
      present size remains a topic of debate. Work along its eastern margin suggests a
      two-stage uplift (thus growth of the plateau) since 30-25 Myr. Here we report
      high-resolution seismic reflection and drill core results from the southern Tarim
      Basin that indicate a similar pattern for the northern margin of the plateau. The
      data suggest that uplift in northern Tibet started at ~23 Myr from near sea
      level, with the first episode finished by ~10 Myr, followed by a post-5-Myr
      episode of rapid uplift along the present plateau margin. The growth of the
      Tibetan Plateau after the Eocene thus appears to have been episodic in nature,
      and near-synchronous along both eastern and northern margins.

PMID- 25391270
TI  - Ultrathin transparent conductive polyimide foil embedding silver nanowires.
AB  - Metallic nanowires are among the most promising transparent conductor (TC)
      alternatives to widely used indium tin oxide (ITO) because of their excellent
      trade-off between electrical and optical properties, together with their
      mechanical flexibility. However, they tend to suffer from relatively large
      surface roughness, instability against oxidation, and poor adhesion to the
      substrate. Embedding in a suitable material can overcome these shortcomings. Here
      we propose and demonstrate a new TC comprising silver nanowires (AgNWs) in an
      ultrathin polyimide foil that presents an optical transmission in the visible
      larger than ITO (>90%), while maintaining similar electrical sheet resistance (15
      ohm/sq). The polyimide protects the Ag against environmental agents such as
      oxygen and water and, thanks to its deformability and very small thickness (5
      MUm), provides an ideal mechanical support to the NW's network, in this way
      ensuring extreme flexibility (bending radius as small as at least 1 mm) and
      straightforwardly removing any adhesion issue. The initial AgNWs' roughness is
      also reduced by a factor of about 15, reaching RMS values as low as 2.4 nm,
      suitable for the majority of applications. All these properties together with the
      simple fabrication technique based on all-solution processing put the developed
      TC in a competitive position as a lightweight, mechanically flexible and
      inexpensive substrate for consumer electronic and optoelectronic devices. 

PMID- 25391271
TI  - Axial InAs/GaAs heterostructures on silicon in a nanowire geometry.
AB  - InAs segments were grown on top of GaAs islands, initially created by droplet
      epitaxy on silicon substrate. We systematically explored the growth-parameter
      space for the deposition of InAs, identifying the conditions for the selective
      growth on GaAs and for purely axial growth. The axial InAs segments were formed
      with their sidewalls rotated by 30 degrees  compared to the GaAs base islands
      underneath. Synchrotron X-ray diffraction experiments revealed that the InAs
      segments are grown relaxed on top of GaAs, with a predominantly zincblende
      crystal structure and stacking faults.

PMID- 25391272
TI  - Mass Gathering Medicine New discipline to Deal with Epidemic and Infectious
      Diseases in the Hajj Among Muslim Pilgrimage: A Mini Review Article.
AB  - Mass Gathering Medicine is one of the new disciplines in Medicine which deal with
      all health aspects in overcrowded areas. Mass Gathering Medicine is an important
      new challenging discipline which needs to be supported by all concern experts
      such as the World Health Organization, Centers for Disease Control and
      Prevention, ministries of health from all countries, universities, research
      centers, and all other experts in this field. Scientist and academic staffs from
      all countries should be encouraged to participate in narrowing the gap of
      knowledge for Mass Gathering Medicine. Postgraduate board or fellowship
      certificate should be encouraged internationally. 

PMID- 25391273
TI  - Development of modified-release tablets of zolpidem tartrate by biphasic
      quick/slow delivery system.
AB  - Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative
      and hypnotic category. It has a short half-life with usual dosage regimen being 5
      mg, two times a day, or 10 mg, once daily. The duration of action is considered
      too short in certain circumstances. Thus, it is desirable to lengthen the
      duration of action. The formulation design was implemented by preparing extended
      release tablets of zolpidem tartrate using the biphasic delivery system
      technology, where sodium starch glycolate acts as a superdisintegrant in
      immediate-release part and hydroxypropyl methyl cellulose as a release retarding
      agent in extended-release core. Tablets were prepared by direct compression. Both
      the core and the coat contained the drug. The pre-compression blends were
      evaluated for angle of repose, bulk density, and compressibility index. The
      tablets were evaluated for thickness, hardness, weight variation test,
      friability, and in vitro release studies. No interaction was observed between
      zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy
      and differential scanning calorimetry analysis. The results of all the
      formulations prepared were compared with reference product Stilnoct(r). Optimized
      formulations showed release patterns that match the United States Pharmacopeia
      (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of
      drug release was studied using different mathematical models, and the optimized
      formulation has shown Fickian diffusion. Accelerated stability studies were
      performed on the optimized formulation. 

PMID- 25391274
TI  - Developing innovative interventions for people with dual diagnosis.

PMID- 25391275
TI  - Gender differences in psychotic disorders with concurrent substance use.
AB  - OBJECTIVE: We conducted a comparative analysis of gender differences in patients
      with primary psychotic disorders with concurrent substance use and in those with
      substance-induced psychoses. METHODS: A total of 385 individuals admitted to
      psychiatric emergency departments with early-onset psychosis and recent substance
      use were interviewed at baseline and at six-month intervals for two years. Using
      a standardized research diagnostic assessment instrument, we classified patients
      at baseline into primary and substance-induced psychosis groups and analyzed the
      effects of gender on demographic, family, and clinical characteristics at
      baseline, the interaction of gender and diagnosis, and gender main effects on
      illness course, adjustment, and service use over the two-year follow-up period.
      RESULTS: Women had better premorbid adjustment, less misattribution of symptoms,
      and a later age at onset of regular drug use compared to men. Women, however,
      showed greater depression and histories of abuse compared to men. Men had greater
      arrest histories. No interactions between gender and diagnosis were significant.
      Both genders in the primary and substance-induced psychosis groups showed
      clinical and functional improvement over the follow-up period despite the overall
      minimal use of mental health and substance abuse treatment services. CONCLUSIONS:
      Women and men with psychosis and substance use differ on several dimensions. Our
      findings suggest the need for gender-specific treatment programming across both
      diagnostic groups.

PMID- 25391276
TI  - Gender, depressive symptoms, and daily cigarette use.
AB  - OBJECTIVE: It is widely known that cigarette use and depressive symptoms co-occur
      during adolescence and young adulthood and that there are gender differences in
      smoking initiation, progression, and co-occurrence with other drug use. Given
      that females have an earlier onset of depressive symptoms while males have an
      earlier onset of cigarette use, this study explored the possible bidirectional
      development of cigarette use and depressive symptoms by gender across the
      transition from adolescence to young adulthood. Gender differences in the
      stability and crossed effects of depressive symptoms and cigarette smoking during
      the transition to young adulthood, controlling for other known risk factors, were
      examined using a nationally representative longitudinal sample. METHODS: A
      bivariate autoregressive multi-group structural equation model examined the
      longitudinal stability and crossed relationships between a latent construct of
      depressive symptoms and cigarette smoking over four waves of data. Data for this
      study came from four waves of participants (N = 6,501) from the National
      Longitudinal Survey of Adolescent Health. At each of four waves, participants
      completed a battery of measures including questions on depressive symptoms and an
      ordinal measure of number of cigarettes smoked per day. RESULTS: The best-fitting
      bivariate autoregressive models were gender-specific, included both crossed and
      parallel associations between depressive symptoms and cigarette use during the
      transition to adulthood, and controlled for wave-specific parental smoking,
      alcohol use, and number of friends who smoke. For females, greater depressive
      symptoms at each wave, except the first one, were associated with greater
      subsequent cigarette use. There were bidirectional associations between
      depressive symptoms and cigarette use only for females during young adulthood,
      but not for males. CONCLUSIONS: The development of depressive symptoms and
      cigarette use from adolescence and into young adulthood follows similar patterns
      for males and females. Controlling for the correlation and stability between
      initial levels of depressive symptoms and cigarette use from adolescence into
      young adulthood, there remains a crossed association between cigarette use and
      depressive symptoms specific to females during young adulthood. The findings
      suggest that prevention interventions focused on mental health should include
      warnings that cigarette use may exacerbate depressive symptoms.

PMID- 25391277
TI  - Remote "hovering" with individuals with psychotic disorders and substance use:
      feasibility, engagement, and therapeutic alliance with a text-messaging mobile
      interventionist.
AB  - OBJECTIVE: People with serious mental illnesses and substance abuse problems
      (i.e., dual diagnosis) constitute a particularly challenging and costly clinical
      group. This study evaluated the feasibility and acceptability of a novel model of
      care in which a mobile interventionist used mobile phone text messaging to
      remotely monitor and provide daily support to individuals with psychotic
      disorders and substance use. METHODS: Seventeen participants with dual diagnosis
      were enrolled in a 12-week single-arm trial. A clinical social worker served as
      the mobile interventionist and sent daily text messages to participants'
      privately owned mobile phones to assess their medication adherence and clinical
      status. The mobile interventionist provided text-message feedback and support and
      suggested various coping strategies flexibly, in response to participants'
      replies to prompts. At the end of the trial, participants completed a usability
      and satisfaction measure and two self-rated measures of therapeutic alliance with
      their clinicians. In one version, participants rated their relationship with
      their mobile interventionist; in the second version, they rated their
      relationship with their community-based treatment team. RESULTS: Participants
      received an average of 139 text messages (SD = 37.5) each from the mobile
      interventionist over the 12-week trial. On average, participants responded to 87%
      of the mobile interventionist's messages that required a reply. More than 90% of
      participants thought the intervention was useful and rewarding and that it helped
      them be more effective and productive in their lives. Participants' assessments
      of their relationship with the mobile interventionist were positive. Paired
      sample t-test found that the therapeutic alliance ratings participants provided
      for their mobile interventionist were significantly higher than those provided
      for their community-based treatment team clinicians, who they met with regularly.
      CONCLUSIONS: Our findings suggest that text-message "hovering" can be conducted
      successfully with individuals with psychotic disorders and substance abuse.
      Developing a cadre of mobile interventionists who are specifically trained on how
      to engage patients via mobile devices while adhering to ethical guidelines and
      regulatory standards may be an effective way to strengthen service delivery
      models, improve patient outcomes, and reduce costs.

PMID- 25391278
TI  - Online comments on smoking bans in psychiatric hospitals units.
AB  - OBJECTIVE: Individuals with mental health concerns are disproportionately
      affected by and suffer the negative consequences of tobacco use disorder, perhaps
      because smoking has historically been part of psychiatry's culture. In the early
      1990s, psychiatric inpatient facilities were exempted from U.S. hospital smoking
      bans, in response to public outcry with national media attention. Almost 2
      decades later, the current study characterizes online conversation about
      psychiatric hospital smoking bans. Previous commenting studies have demonstrated
      commenting's negativity, documenting the "nasty effect" wherein negative comments
      color perceptions of neutral articles. Thus, we focused particular attention on
      cited barriers to implementing health-positive smoke-free policies. METHODS: We
      collected online comments (N = 261) responding to popular media articles on
      smoking bans in inpatient psychiatry between 2013 and 2014 and conducted an
      inductive and exploratory qualitative content analysis. RESULTS: Verifying
      previous studies documenting the prevalence of negative commenting, of the
      comments explicitly supporting or refuting psychiatry smoking bans, there were
      over twice as many con comments (n = 44) than pro (n = 18). Many commenters
      argued for access to outdoor smoking areas and warned of patient agitation and
      risk posed to care workers. Identified content themes included psychiatric
      medication and negative side effects, broken mental health systems and
      institutions, denigration of the health risks of tobacco in the context of mental
      illness, typical pro-smoking arguments about "smokers' rights" and alternatives
      (including e-cigarettes), addiction, and stigma. CONCLUSIONS: The current
      findings provide a platform to begin to understand how people talk about mental
      health issues and smoking. Our analysis also raised complex issues concerning
      forces that impact U.S. patients with serious mental illness but over which they
      have little control, including medication, the U.S. health system, stigma,
      perceptions that life with chronic serious mental illness is not worth living,
      and psychological and physical pain of coping with mental illness. In
      consideration of identified barriers raised in opposition to smoking bans in
      inpatient psychiatry, efforts should emphasize patient stakeholder involvement;
      patient, visitor, and staff protection from smoke exposure; the effectiveness of
      nicotine replacement for managing withdrawal; and the lack of evidence that
      cigarettes are therapeutic.

PMID- 25391279
TI  - Long-term sobriety strategies for men with co-occurring disorders.
AB  - OBJECTIVE: Roughly half of people with severe mental disorders also experience a
      co-occurring substance use disorder, and recovery from both is a critical
      objective for health care services. While understanding of abstinence initiation
      has grown, the strategies people with co-occurring disorders use to maintain
      sobriety are largely unknown. This article reports strategies for relapse
      prevention as described by men with co-occurring disorders who achieved one or
      more years of sobriety. METHODS: We analyzed semi-structured interviews conducted
      with a sample of 12 men with co-occurring psychosis and substance use disorder
      who achieved and maintained sobriety for at least one year, supplemented with
      demographic and diagnostic clinical record data. These men were participating in
      residential or outpatient treatment at a private, nonprofit integrated treatment
      clinic. RESULTS: The 12 men were primarily Caucasian (91.7%) and unmarried
      (100%), and their ages ranged from 23 to 42 years. The two most common
      psychiatric disorders were schizoaffective disorder (n = 4, 33.3%) and bipolar
      disorder (n = 4, 33.3%), while the two most commonly misused substances were
      alcohol and cannabis. Qualitative analyses showed that participants maintained
      sobriety for at least one year by building a supportive community, engaging in
      productive activities, and carefully monitoring their own attitudes toward
      substances, mental health, and responsibility. Alcoholics Anonymous might act as
      a catalyst for building skills. CONCLUSIONS: People with co-occurring disorders
      who achieve sobriety use a variety of self-management strategies to prevent
      relapse-seeking support, activities, and a healthy mindset. The findings suggest
      a relapse prevention model that focuses on social networks, role functioning, and
      self-monitoring and conceptualizes self-care as critical to extending periods of
      wellness.

PMID- 25391280
TI  - A qualitative study of career exploration among young adult men with psychosis
      and co-occurring substance use disorder.
AB  - OBJECTIVE: This article explores the meaning and importance of career exploration
      and career development in the context of integrated treatment for young adults
      with early psychosis and substance use disorders (i.e., co-occurring disorders).
      METHODS: Twelve young adult men (aged 18 to 35 years) with co-occurring disorders
      recruited from an integrated treatment center completed a series of three semi
      structured in-depth qualitative interviews. Data were transcribed verbatim and
      analyzed using thematic analysis. Purposive sampling ensured participants
      represented a range of substance abuse treatment stages. RESULTS: Participants
      had a mean age of 26 (SD = 3) and identified as White. Two-thirds of participants
      (n = 8, 67%) had diagnosed schizophrenia-spectrum disorders, three (25%) had
      bipolar disorder, and one (8%) had major depression; four (33%) also had a co
      occurring anxiety disorder. The most common substance use disorders involved
      cannabis (n = 8, 67%), cocaine (n = 5, 42%), and alcohol (n = 5, 42%). These
      young adult men with co-occurring disorders described past jobs that did not
      align with future goals as frustrating and disempowering, rather than confidence
      building. Most young adult participants began actively developing their careers
      in treatment through future-oriented work or school placements. They pursued
      ambitious career goals despite sporadic employment and education histories.
      Treatment engagement and satisfaction appeared to be linked with career
      advancement prospects. CONCLUSIONS: Integrating career planning into psychosocial
      treatment is a critical task for providers who serve young adults with co
      occurring disorders. Whether integrating career planning within early
      intervention treatment planning will improve clinical, functional, or economic
      outcomes is a promising area of inquiry for rehabilitation researchers and
      clinicians.

PMID- 25391281
TI  - Motivational interviewing for smoking cessation in a psychiatric day hospital: a
      feasibility study.
AB  - OBJECTIVE: Our main objective was to test the feasibility of adding motivational
      interviewing to the usual smoking cessation treatment for patients with
      psychiatric disorders attending a day hospital. METHODS: A total of 44 patients
      participated in the study: a comparison group of 25 patients, all of whom
      received the usual smoking cessation treatment (nicotine replacement therapy, 1
      hour of weekly group therapy, and daily individual advice), and an intervention
      group of 19 patients who received the usual smoking cessation treatment plus up
      to four motivational interviewing sessions. Data included sociodemographics,
      psychiatric diagnosis, cigarette use, and engagement in treatment. Descriptive
      analyses were conducted, along with logistic regression to test for differences
      on abstinence and daily smoking rates. RESULTS: All 19 patients offered the
      motivational interviewing accepted it, and all of them completed at least one
      session (M = 2.53, SD = 0.234, Range = 1 to 4). At the end of treatment, four
      patients in the intervention group were abstinent (versus none in the comparison
      group), but this was not statistically significant. Both groups showed a mean
      daily reduction of eight cigarettes. After introducing all variables into the
      regression models, none reached significance. CONCLUSIONS: Adding motivational
      interviewing to usual smoking cessation treatment in a psychiatric day hospital
      seems feasible and acceptable. Further, more rigorous research is needed.

PMID- 25391284
TI  - General practitioners' perceptions of and involvement in health behaviour change:
      can computer-tailored interventions help?
AB  - AIM: To explore GPs' perceptions of their role in primary prevention, barriers
      experienced and willingness to accommodate an automated, computer-tailored
      intervention. BACKGROUND: General practice is an attractive setting for primary
      prevention of chronic disease. Due to constraints in time and knowledge it is
      underutilised. METHODS: Telephone interviews of 13 GPs in Brisbane, Australia,
      whose patients were previously involved in a lifestyle change research project.
      Qualitative responses were grouped into themes. FINDINGS: GPs perceived their
      role in lifestyle change as 'educators', 'supporters' and 'prompters'. Smoking
      and physical activity were addressed more often than alcohol and salt intake.
      Longer lifestyle-focussed consultations and computer-generated reminders were
      suggested to overcome barriers. A computer-tailored approach was appreciated due
      to its minimal impact on practice routine. GPs understand their role in primary
      prevention but need help to overcome barriers. GP initiated consultations
      focusing on lifestyle and prevention along with computer support systems could
      improve capability for prevention in general practice.

PMID- 25391283
TI  - The Wisconsin Assessment of the Social and Built Environment (WASABE): a multi
      dimensional objective audit instrument for examining neighborhood effects on
      health.
AB  - BACKGROUND: Growing evidence suggests that mixed methods approaches to measuring
      neighborhood effects on health are needed. The Wisconsin Assessment of the Social
      and Built Environment (WASABE) is an objective audit tool designed as an addition
      to a statewide household-based health examination survey, the Survey of the
      Health of Wisconsin (SHOW), to objectively measure participant's neighborhoods.
      METHODS: This paper describes the development and implementation of the WASABE
      and examines the instrument's ability to capture a range of social and built
      environment features in urban and rural communities. A systematic literature
      review and formative research were used to create the tool. Inter-rater
      reliability parameters across items were calculated. Prevalence and density of
      features were estimated for strata formed according to several sociodemographic
      and urbanicity factors. RESULTS: The tool is highly reliable with over 81% of 115
      derived items having percent agreement above 95%. It captured variance in
      neighborhood features in for a diverse sample of SHOW participants. Sidewalk
      density in neighborhoods surrounding households of participants living at less
      than 100% of the poverty level was 67% (95% confidence interval, 55-80%) compared
      to 34% (25-44%) for those living at greater than 400% of the poverty level.
      Walking and biking trails were present in 29% (19-39%) of participant buffer in
      urban areas compared to only 7% (2-12%) in rural communities. Significant
      environmental differences were also observed for white versus non-white, high
      versus low income, and college graduates versus individuals with lower level of
      education. CONCLUSIONS: The WASABE has strong inter-rater reliability and
      validity properties. It builds on previous work to provide a rigorous and
      standardized method for systematically gathering objective built and social
      environmental data in a number of geographic settings. Findings illustrate the
      complex milieu of built environment features found in participants neighborhoods
      and have relevance for future research, policy, and community engagement
      purposes.

PMID- 25391285
TI  - Creating a tenuous balance: siblings' experience of a brother's or sister's
      childhood cancer diagnosis.
AB  - More than 14,000 children are diagnosed with cancer in the United States each
      year. Prolonged, intensive treatment protocols disrupt the entire family,
      including siblings. Here, we employed grounded theory methodology to examine the
      experiences of 30 nonbereaved adolescent siblings of children receiving cancer
      treatment. The central organizing theme of the emergent data is "creating a
      tenuous balance." Contributing themes include (a) knowing something is seriously
      wrong, (b) figuring out the meaning of cancer, (c) adapting to changes in
      personal and family life, and (d) handling emotional reactions to cancer.
      Overall, findings suggest an ongoing, active process by which siblings notice and
      adapt to the many unexpected and taxing aspects of their brother's or sister's
      cancer diagnosis and treatment, including shifts in how the family system
      operates. Findings highlight the important role of siblings in family-centered
      cancer care. Future, larger scale research should develop targeted interventions
      for these siblings. 

PMID- 25391286
TI  - Delayed posterior fossa epidural hematoma originating from occipital artery after
      infratentorial craniotomy.

PMID- 25391287
TI  - Transient ventricular flutter in Devic's syndrome during hysteroscopy under
      anesthesia.

PMID- 25391288
TI  - Formulation, characterization and evaluation of cyclodextrin-complexed
      bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer
      treatment.
AB  - PLGA nanospheres are considered to be promising drug carrier in the treatment of
      cancer. Inclusion complex of bendamustine (BM) with epichlorohydrin beta
      cyclodextrin polymer was prepared by freeze-drying method. Phase solubility study
      revealed formation of AL type complex with stability constant (Ks = 645 M(-1)).
      This inclusion complex was encapsulated into PLGA nanospheres using solid-in-oil
      in-water (S/O/W) technique. The particle size and zeta potential of PLGA
      nanospheres loaded with cyclodextrin-complexed BM were about 151.4 +/- 2.53 nm
      and - 31.9 +/- (-3.08) mV. In-vitro release study represented biphasic release
      pattern with 20% burst effect and sustained slow release. DSC studies indicated
      that inclusion complex incorporated in PLGA nanospheres was not in a crystalline
      state but existed in an amorphous or molecular state. The cytotoxicity experiment
      was studied in Z-138 cells and IC50 value was found to be 4.3 +/- 0.11 uM. Cell
      viability studies revealed that the PLGA nanospheres loaded with complex exerts a
      more pronounced effect on the cancer cells as compared to the free drug. In
      conclusion, PLGA nanospheres loaded with inclusion complex of BM led to sustained
      drug delivery. The nanospheres were stable after 3 months of storage conditions
      with slight change in their particle size, zeta potential and entrapment
      efficiency.

PMID- 25391289
TI  - Medical students' assessment of pediatric patients - teaching and evaluation
      using video cases.
AB  - BACKGROUND: We introduced video-based teaching in pediatrics. We evaluated the
      impact of a pediatric video program on student performance in assessing pediatric
      patients presented as video cases. The program consisted of a library of
      pediatric videos, and inclusion of these in the teaching and examination for
      pediatric medicine. METHODS: Medical students on a pediatric clerkship at the
      University of Copenhagen assessed eight short pediatric video cases during autumn
      2011 and spring 2012. Two independent observers evaluated a subset of records in
      a pilot study. A blind evaluation was made of the written records of 37 students
      before, and 58 students after, the introduction of the program using a Rubric
      score with four domains. RESULTS: The intraobserver interclass correlation
      coefficient was 0.94 and the interobserver interclass correlation was 0.71(n=25).
      The students' mean total Rubric score in spring 2012 (7.0) was significantly
      higher (p<0.001, 95% CI 1.34-3.20) than autumn 2011 (4.7). Cohen's d was 1.1 (95%
      CI 0.6-1.7). Single domains scores increased significantly for general assessment
      (1.30 versus 0.57) (p<0.002, 95% CI 0.45-1.18), recognition of principal symptoms
      (1.38 versus 0.81) (p<0.008, 95% CI 0.22-0.91), appropriate diagnosis (2.28
      versus 1.78) (p<0.002, 95% CI 0.16-0.82) and consistency between observed
      symptoms and diagnosis (1.94 versus 1.57) (p=0.0482, 95% CI 0.00-0.79).
      CONCLUSIONS: Students improved in evaluating pediatric patients presented as
      video cases after the introduction of the program. The impact on real-life
      situations remains to be established.

PMID- 25391290
TI  - A theory-based intervention to improve breast cancer awareness and screening in
      Jamaica.
AB  - Despite declines in breast cancer mortality rates in developed countries,
      mortality rates remain high in Jamaica due to low levels of screening and lack of
      early detection. We hypothesized that a theory-based health educational
      intervention would increase awareness of breast cancer and intention to screen
      among women in Western Jamaica. Two hundred and forty six women attending
      hospitals or clinics were enrolled in an educational intervention consisting of a
      pretest, breast cancer presentation, and posttest if they had never been screened
      or had not been screened in 5 years or more. The questionnaires assessed
      attitudes and knowledge of risk factors and symptoms related to breast cancer.
      Participants were followed approximately 6 months after the intervention to
      determine whether they accessed breast cancer screening. There were statistically
      significant increases (p < 0.0001) in the percentage of correct knowledge
      responses and in participants' intention to screen from pretest to posttest. The
      greatest posttest improvements were among items measuring knowledge of breast
      cancer screening tests and risk factors. Of the 134 women who were reached by
      phone for post-intervention follow-up, 30 women (22.4 %) were screened for breast
      cancer and 104 women (77.6 %) had not been screened. The use of a theory-based
      educational intervention positively influenced knowledge of breast cancer risk
      factors, symptoms, and types of screening and increased screening rates in
      screening-naive women. This theory-based educational intervention may be
      replicated to promote awareness of breast cancer and further increase screening
      rates in other areas of Jamaica and other developing countries.

PMID- 25391291
TI  - Mutagenicity and tumor-promoting effects of Tiglium seed extract via PKC and MAPK
      signaling pathways.
AB  - Tiglium seed is a seed of mature Croton Tiglium Linne containing croton oils,
      which have been traditionally used as laxative or purgative. As it contains
      phorbol derivatives, we investigated the mutagenicity and tumor-promoting
      activity of Tiglium seed. Tiglium seed extract produced the mutagenic responses
      in five Salmonella typhimurium strains in Ames assay, whereas it did not alter
      the frequencies of chromosomal aberrations or micronuclei, indicating that it
      exerted the mutagenic potential, not clastogenicity. Accompanied with
      phosphorylation of connexin43 (Cx43) and extracellular signal-regulated kinases
      1/2 (ERK1/2), Tiglium seed extract inhibited gap junctional intercellular
      communication (GJIC) associated with tumor-promoting potential. Importantly,
      these effects were blocked by a protein kinase C (PKC) inhibitor or mitogen
      activated protein kinase (MAPKs) inhibitors, suggesting that Tiglium seed-induced
      GJIC inhibition was regulated by phosphorylation of Cx43 via PKC and MAPKs
      signaling. In conclusion, Tiglium seed has mutagenicity, possibly linking to
      tumor-promoting potential through the dysfunction of GJIC. 

PMID- 25391292
TI  - Investigating the role of acute mental stress on endothelial dysfunction: a
      systematic review and meta-analysis.
AB  - Chronic stress is a known risk factor for both endothelial dysfunction and
      cardiovascular disease (CVD), but less is known of how acute mental stress
      affects the vasculature. In this systematic review and meta-analysis, we analyzed
      the impact of acute mental stress on flow-mediated dilation (FMD), an indicator
      of endothelial function. We searched the Medline, Cochrane, EMBASE, and ISI Web
      of Knowledge databases through May 2014, to identify publications in English
      language journals. The primary outcome was the change in FMD from baseline to the
      time of measurement. We also assessed the risk of bias and the heterogeneity of
      included studies. Our search identified eight prospective studies, which
      displayed significant heterogeneity. Four studies measured FMD while the subject
      was performing the task; six measured FMD after the task had been completed. The
      total number of participants was 164. The pooled results indicate that FMD did
      not change significantly while the task was being performed (pooled difference in
      means: -0.853; 95 % confidence interval (CI), -3.926/2.220; P = 0.586); however,
      FMD measured after the task was completed was significantly less than baseline
      (pooled difference in means: -2.450; 95 %CI, -3.925/-0.975; P = 0.001). In
      conclusions, our findings provide evidence that an acute stressful experience has
      a delayed, negative impact on the function of the endothelium. Repeated exposure
      to short-term stress may lead to permanent injury of the vasculature. Therefore,
      assessment of patients' exposure to both repeated acute mental stress and chronic
      stress may be useful in determining their risk of developing CVD.

PMID- 25391293
TI  - Resolution of aortic root thrombosis in a patient treated with veno-arterial
      extracorporeal membrane oxygenation.

PMID- 25391294
TI  - Sumoylation of p35 modulates p35/cyclin-dependent kinase (Cdk) 5 complex
      activity.
AB  - Cyclin-dependent kinase (Cdk) 5 is critical for central nervous system
      development and neuron-specific functions including neurite outgrowth as well as
      synaptic function and plasticity. Cdk5 activity requires association with one of
      the two regulatory subunits, called p35 and p39. p35 redistribution as well as
      misregulation of Cdk5 activity is followed by cell death in several models of
      neurodegeneration. Posttranslational protein modification by small ubiquitin
      related modifier (SUMO) proteins (sumoylation) has emerged as key regulator of
      protein targeting and protein/protein interaction. Under cell-free in vitro
      conditions, we found p35 covalently modified by SUMO1. Using both biochemical and
      FRET-/FLIM-based approaches, we demonstrated that SUMO2 is robustly conjugated to
      p35 in cells and identified the two major SUMO acceptor lysines in p35, K246 and
      K290. Furthermore, different degrees of oxidative stress resulted in differential
      p35 sumoylation, linking oxidative stress that is encountered in
      neurodegenerative diseases to the altered activity of Cdk5. Functionally,
      sumoylation of p35 increased the activity of the p35/Cdk5 complex. We thus
      identified a novel neuronal SUMO target and show that sumoylation is a likely
      candidate mechanism for the rapid modulation of p35/Cdk5 activity in
      physiological situations as well as in disease. 

PMID- 25391295
TI  - The association of asthma education centre characteristics on hospitalizations
      and emergency department visits in Ontario: a population-based study.
AB  - BACKGROUND: International guidelines recommend patient education as an essential
      component of optimal asthma management. Since 1990 hospital-based asthma
      education centres (AECs) have been established in Ontario, Canada. It is unknown
      whether patient outcomes are related to the level of services provided. METHODS:
      Using linked, population-based health administrative and hospital survey data we
      analyzed a population of patients aged 2 to 55 years with a hospitalization for
      asthma (N = 12 029) or a high acuity asthma emergency department (ED) visit (N =
      63 025) between April 2004 and March 2007 and followed for three years.
      Administrative data documenting individuals' attendance at AECs were not
      available. Poisson models were used to test the association of potential access
      to various AEC service models (outpatient service availability and in-hospital
      services) with asthma readmissions, ED visits or death within 6 to 36 months
      following the index admission or ED visit. RESULTS: Fifty three of 163 acute care
      hospitals had an AEC (N = 36) or had access by referral (N = 17). All AECs
      documented use with guideline-based recommendations for AE programs. ED patients
      having access to an AEC that offered full-time, extended hours had reduced rates
      of adverse outcomes (adjusted relative rate [aRR] 0.78, 95% confidence interval
      [CI] 0.69, 0.90) compared to those with no AEC access. Hospitalized patients with
      access to asthma education during hospitalization had reduced rates of adverse
      events (aRR 0.87, 95% CI 0.75, 1.00) compared to those with no inhospital AEC
      access. CONCLUSION: Although compliant with asthma guideline-based program
      elements, on a population basis access to asthma education centres is associated
      only with a modest benefit for some admitted and ED patients and depends on the
      level of access to services provided. Review of both services provided and
      strategies to address potential barriers to care are necessary.

PMID- 25391296
TI  - Effect of aminoguanidine on sciatic functional index, oxidative stress, and rate
      of apoptosis in an experimental rat model of ischemia-reperfusion injury.
AB  - This study was conducted to investigate the potential protective effects of
      aminoguanidine (AG) on sciatic functional index (SFI), oxidative stress status,
      and apoptosis index using a rat model of experimental sciatic nerve ischemia
      reperfusion injury (I/R). Treatment groups received 150 mg AG/kg body mass, 24 h
      after the induction of ischemia. After reperfusion for 2, 4, 7, 14, and 28 days,
      we evaluated measured SFI, plasma antioxidant enzymes, total antioxidant capacity
      (TAC), malondialdehyde (MDA), and index of apoptosis. SFI was significantly
      improved on the 7th and 14th day of reperfusion in the AG-treated groups. AG
      treatment resulted in the significant reduction of MDA levels on the 7th and 14th
      day of reperfusion. TAC was only increased after 7 days of reperfusion compared
      with the untreated group. SOD activity was decreased in both the untreated and AG
      treated groups by comparison with the control, but did not show a significant
      change. GPx activity decreased only after 7 days of reperfusion. The maximal rate
      of apoptosis occurred on the 7th day of reperfusion. Treatment with AG
      significantly reduced this enhancement. AG exhibits positive effects against
      sciatic nerve I/R injury, possibly in part because of the protective effects of
      AG against apoptosis and I/R-induced oxidative stress. 

PMID- 25391297
TI  - Limited role of regulatory T cells during acute Theiler virus-induced
      encephalitis in resistant C57BL/6 mice.
AB  - BACKGROUND: Theiler's murine encephalomyelitis virus (TMEV) infection represents
      a commonly used infectious animal model to study various aspects of the
      pathogenesis of multiple sclerosis (MS). In susceptible SJL mice, dominant
      activity of Foxp3(+) CD4(+) regulatory T cells (Tregs) in the CNS partly
      contributes to viral persistence and progressive demyelination. On the other
      hand, resistant C57BL/6 mice rapidly clear the virus by mounting a strong
      antiviral immune response. However, very little is known about the role of Tregs
      in regulating antiviral responses during acute encephalitis in resistant mouse
      strains. METHODS: In this study, we used DEREG mice that express the diphtheria
      toxin (DT) receptor under control of the foxp3 locus to selectively deplete
      Foxp3(+) Tregs by injection of DT prior to infection and studied the effect of
      Treg depletion on the course of acute Theiler's murine encephalomyelitis (TME).
      RESULTS: As expected, DEREG mice that are on a C57BL/6 background were resistant
      to TMEV infection and cleared the virus within days of infection, regardless of
      the presence or absence of Tregs. Nevertheless, in the absence of Tregs we
      observed priming of stronger effector T cell responses in the periphery, which
      subsequently resulted in a transient increase in the frequency of IFNgamma
      producing T cells in the brain at an early stage of infection. Histological and
      flow cytometric analysis revealed that this transiently increased frequency of
      brain-infiltrating IFNgamma-producing T cells in Treg-depleted mice neither led
      to an augmented antiviral response nor enhanced inflammation-mediated tissue
      damage. Intriguingly, Treg depletion did not change the expression of IL-10 in
      the infected brain, which might play a role for dampening the inflammatory damage
      caused by the increased number of effector T cells. CONCLUSION: We therefore
      propose that unlike susceptible mice strains, interfering with the Treg
      compartment of resistant mice only has negligible effects on virus-induced
      pathologies in the CNS. Furthermore, in the absence of Tregs, local anti
      inflammatory mechanisms might limit the extent of damage caused by strong anti
      viral response in the CNS.

PMID- 25391298
TI  - Energy status and HIF signalling in chorionic villi show no evidence of hypoxic
      stress during human early placental development.
AB  - Early human placental and embryonic development occurs in a physiologically low
      oxygen environment supported by histiotrophic secretions from endometrial glands.
      In this study, we compare the placental metabolomic profile in the first, second
      and third trimesters to determine whether the energy demands are adequately met
      in the first trimester. We investigated whether hypoxia-inducible factors, HIF
      1alpha and/or HIF-2alpha, might regulate transcription during the first
      trimester. First and second trimester tissue was collected using a chorionic
      villus sampling-like (CVS) technique. Part of each villus sample was frozen
      immediately and the remainder cultured under 2 or 21% O2 +/- 1 mM H2O2, and +/
      the p38 MAPK pathway inhibitor, PD169316. Levels of HIF-1alpha were assessed by
      western blotting and VEGFA, PlGF and GLUT3 transcripts were quantified by RT-PCR.
      Term samples were collected from normal elective Caesarean deliveries. There were
      no significant differences in concentrations of ADP, NAD(+), lactate, and
      glucose, and in the ATP/ADP ratio, across gestational age. Neither HIF-1alpha nor
      HIF-2alpha could be detected in time-zero CVS samples. However, culture under any
      condition (2 or 21% O2 +/- 1 mM H2O2) increased HIF-1alpha and HIF-2alpha. HIF
      1alpha and HIF-2alpha were additionally detected in specimens retrieved after
      curettage. HIF-1alpha stabilization was accompanied by significant increases in
      VEGFA and GLUT3 and a decrease in PlGF mRNAs. These effects were suppressed by
      PD169316. In conclusion, our data suggest that first trimester placental tissues
      are not energetically compromised, and that HIF-1alpha is unlikely to play an
      appreciable role in regulating transcriptional activity under steady-state
      conditions in vivo. However, the pathway may be activated by stress conditions. 

PMID- 25391299
TI  - Human embryonic stem cells carrying an unbalanced translocation demonstrate
      impaired differentiation into trophoblasts: an in vitro model of human
      implantation failure.
AB  - Carriers of the balanced translocation t(11;22), the most common reciprocal
      translocation in humans, are at high risk of creating gametes with unbalanced
      translocation, leading to repeated miscarriages. Current research models for
      studying translocated embryos and the biological basis for their implantation
      failure are limited. The aim of this study was to elucidate whether human
      embryonic stem cells (hESCs) carrying the unbalanced chromosomal translocation
      t(11;22) can provide an explanation for repeated miscarriages of unbalanced
      translocated embryos. Fluorescent in situ hybridization and karyotype analysis
      were performed to analyze the t(11;22) in embryos during PGD and in the derived
      hESC line. The hESC line was characterized by RT-PCR and FACS analysis for
      pluripotent markers. Directed differentiation to trophoblasts was carried out by
      bone morphogenetic protein 4 (BMP4). Trophoblast development was analyzed by
      measuring beta-hCG secretion, by beta-hCG immunostaining and by gene expression
      of trophoblastic markers. We derived the first hESC line carrying unbalanced
      t(11;22), which showed the typical morphological and molecular characteristics of
      a hESC line. Control hESCs differentiated into trophoblasts secreted increasing
      levels of beta-hCG and concomitantly expressed the trophoblast genes, CDX2, TP63,
      KRT7, ERVW1, CGA, GCM1, KLF4 and PPARG. In contrast, differentiated translocated
      hESCs displayed reduced and delayed secretion of beta-hCG concomitant with
      impaired expression of the trophoblastic genes. The reduced activation of
      trophoblastic genes may be responsible for the impaired trophoblastic
      differentiation in t(11;22)-hESCs, associated with implantation failure in
      unbalanced t(11;22) embryos. Our t(11;22) hESCs are presented as a valuable human
      model for studying the mechanisms underlying implantation failure. 

PMID- 25391300
TI  - Noise masking of S-cone increments and decrements.
AB  - S-cone increment and decrement detection thresholds were measured in the presence
      of bipolar, dynamic noise masks. Noise chromaticities were the L-, M-, and S-cone
      directions, as well as L-M, L+M, and achromatic (L+M+S) directions. Noise
      contrast power was varied to measure threshold Energy versus Noise (EvN)
      functions. S+ and S- thresholds were similarly, and weakly, raised by achromatic
      noise. However, S+ thresholds were much more elevated by S, L+M, L-M, L- and M
      cone noises than were S- thresholds, even though the noises consisted of two
      symmetric chromatic polarities of equal contrast power. A linear cone combination
      model accounts for the overall pattern of masking of a single test polarity well.
      L and M cones have opposite signs in their effects upon raising S+ and S-
      thresholds. The results strongly indicate that the psychophysical mechanisms
      responsible for S+ and S- detection, presumably based on S-ON and S-OFF pathways,
      are distinct, unipolar mechanisms, and that they have different spatiotemporal
      sampling characteristics, or contrast gains, or both. 

PMID- 25391301
TI  - The external noise normalized gain profile of spatial vision.
AB  - The contrast sensitivity function (CSF), a measure of visual sensitivity to a
      wide range of spatial frequencies, has been widely used as the gain profile of
      the front-end filter of the visual system to predict how we perceive spatial
      patterns. However, the CSF itself is determined by the gain profile and other
      processing inefficiencies of the visual system; it may be problematic to use the
      CSF as the gain profile in observer models. Here, we applied the external noise
      paradigm and the perceptual template model (PTM) to characterize several major
      properties of the visual system. With the external noise normalized gain profile,
      nonlinearity, and internal additive and multiplicative noises, the PTM accounted
      for 92.8% of the variance in the experiment data measured in a wide range of
      conditions and revealed the major processing components that determine the CSF.
      Unlike the CSF, the external noise normalized gain profile of the visual system
      is relatively flat across a wide range of spatial frequencies. The results may
      have major implications for understanding normal and abnormal spatial vision. 

PMID- 25391303
TI  - Physician implementation of asthma management guidelines and recommendations: 2
      case studies.
AB  - Despite the development and availability of new treatments and prescription
      medications, asthma remains a widespread chronic health problem in the United
      States. Achieving asthma control in patients is a resource-intensive enterprise
      that requires close assessment and personalized management. Asthma is simply not
      a disease that can be remedied with prescription medications alone. In 2007, the
      National Asthma Education and Prevention Program released their Guidelines for
      the Diagnosis and Management of Asthma. The guidelines provide assistance and
      direction to health care professionals in the assessment and treatment of
      patients with asthma. Two cases are presented to illustrate the treatment process
      in light of the Guidelines and the outcomes of these patients, who have varying
      degrees of support, education, and assessment of adherence to an asthma treatment
      plan. 

PMID- 25391304
TI  - Altered functional connectivity in seizure onset zones revealed by fMRI intrinsic
      connectivity.
AB  - OBJECTIVE: The purpose of this study was to investigate functional connectivity
      (FC) changes in epileptogenic networks in intractable partial epilepsy obtained
      from resting-state fMRI by using intrinsic connectivity contrast (ICC), a voxel
      based network measure of degree that reflects the number of connections to each
      voxel. METHODS: We measured differences between intrahemispheric- and
      interhemispheric-ICC (ICCintra-inter) that could reveal localized connectivity
      abnormalities in epileptogenic zones while more global network changes would be
      eliminated when subtracting these values. The ICCintra-inter map was compared
      with the seizure onset zone (SOZ) based on intracranial EEG (icEEG) recordings in
      29 patients with at least 1 year of postsurgical follow-up. Two independent
      reviewers blindly interpreted the icEEG and fMRI data, and the concordance rates
      were compared for various clinical factors. RESULTS: Concordance between the
      icEEG SOZ and ICCintra-inter map was observed in 72.4% (21/29) of the patients,
      which was higher in patients with good surgical outcome, especially in those
      patients with temporal lobe epilepsy (TLE) or lateral temporal seizure
      localization. Concordance was also better in the extratemporal lobe epilepsy than
      the TLE group. In 85.7% (18/21) of the cases, the ICCintra-inter values were
      negative in the SOZ, indicating decreased FC within the epileptic hemisphere
      relative to between hemispheres. CONCLUSIONS: Assessing alterations in FC using
      fMRI-ICC map can help localize the SOZ, which has potential as a noninvasive
      presurgical diagnostic tool to improve surgical outcome. In addition, the method
      reveals that, in focal epilepsy, both intrahemispheric- and interhemispheric-FC
      may be altered, in the presence of both regional as well as global network
      abnormalities.

PMID- 25391306
TI  - Early haemoperfusion with continuous venovenous haemofiltration improves survival
      of acute paraquat-poisoned patients.
AB  - OBJECTIVE: To determine whether haemoperfusion (HP) with continuous venovenous
      haemofiltration (CVVH) improves the survival of patients with acute paraquat
      poisoning, compared with those treated using HP alone. METHODS: Medical records
      of patients with acute paraquat poisoning were analysed. Patients were randomised
      to undergo HP or HP + CVVH within 24 h of paraquat ingestion. Mortality rate,
      survival duration and cause of death were recorded. RESULTS: There were no
      significant differences in mortality rate between the HP group (n = 458) and the
      HP + CVVH group (n = 226) (57.4% and 58.4%, respectively). The mean survival
      duration was significantly longer in the HP + CVVH group than the HP group (8.6
      +/- 3.1 and 5.1 +/- 2.3 days, respectively). Early circulatory collapse was a
      major cause of death in the HP group. The major cause of death in the HP + CVVH
      group was late respiratory failure. CONCLUSION: Combined therapy with HP and CVVH
      can prevent early death and prolong survival duration following acute paraquat
      poisoning, providing the opportunity for further treatment.

PMID- 25391305
TI  - Results of 2-year vitamin B treatment on cognitive performance: secondary data
      from an RCT.
AB  - OBJECTIVE: We investigated the effects of 2-year folic acid and vitamin B12
      supplementation on cognitive performance in elderly people with elevated
      homocysteine (Hcy) levels. METHODS: This multicenter, double-blind, randomized,
      placebo-controlled trial included 2,919 elderly participants (65 years and older)
      with Hcy levels between 12 and 50 umol/L. Participants received daily either a
      tablet with 400 ug folic acid and 500 ug vitamin B12 (B-vitamin group) or a
      placebo tablet. Both tablets contained 15 ug vitamin D3. Data were available for
      global cognitive functioning assessed by Mini-Mental State Examination (n =
      2,556), episodic memory (n = 2,467), attention and working memory (n = 759),
      information processing speed (n = 731), and executive function (n = 721).
      RESULTS: Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95%
      confidence interval -5.3 to -4.7) umol/L in the B-vitamin group and 1.3 (-1.6 to 
      0.9) umol/L in the placebo group. Cognitive domain scores did not differ over
      time between the 2 groups, as determined by analysis of covariance. Mini-Mental
      State Examination score decreased with 0.1 (-0.2 to 0.0) in the B-vitamin group
      and 0.3 (-0.4 to -0.2) in the placebo group (p = 0.05), as determined by an
      independent t test. CONCLUSIONS: Two-year folic acid and vitamin B12
      supplementation did not beneficially affect performance on 4 cognitive domains in
      elderly people with elevated Hcy levels. It may slightly slow the rate of decline
      of global cognition, but the reported small difference may be attributable to
      chance. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that 2
      year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic
      elderly people does not affect cognitive performance.

PMID- 25391307
TI  - A dissolved oxygen dressing: a pilot study in an ischemic skin flap model.
AB  - OBJECTIVES: To determine if skin flap failure rates could be improved with the
      use of a dissolved oxygen wound dressing in a porcine model. METHODS: Full
      thickness skin flaps (4 * 16 cm) were raised on pigs. Flaps were randomly
      assigned after surgery to experimental treatment with a dissolved oxygen dressing
      (treatment group) or a hydrogel dressing (control group). Flaps were evaluated
      daily for 14 days. Skin flaps that failed any one of four key clinical outcomes
      were considered failures. Histological parameters (including skin and
      subcutaneous necrosis, inflammation, ischemia, fibrosis, and bacterial load) were
      compared by a blinded histopathologist. RESULTS: Sixteen full-thickness skin
      flaps were raised on four pigs. All animals survived surgery and all incisions
      were evaluable. Clinical flap failure was observed in six (75%) control-treated
      wounds and in two (25%) dissolved oxygen-treated wounds. Histological evaluation
      demonstrated no significant differences in the proximal 75% of the flaps. There
      were significant differences in a number of histological parameters in the distal
      25% in favor of the dissolved oxygen dressing. CONCLUSIONS: Flaps treated with a
      dissolved oxygen dressing had fewer clinical failures and improved histological
      profiles compared with control-treated flaps, suggesting that increasing local
      oxygen supply may improve the local wound healing environment.

PMID- 25391308
TI  - SWI/SNF proteins as targets in cancer therapy.
AB  - Recent identification of synthetic lethal interactions involving several proteins
      of the SWI/SNF complex discussed in this Research Highlight has opened the
      possibility of new cancer therapeutic approaches. 

PMID- 25391309
TI  - Acoustic and foraging behavior of a Baird's beaked whale, Berardius bairdii,
      exposed to simulated sonar.
AB  - Beaked whales are hypothesized to be particularly sensitive to anthropogenic
      noise, based on previous strandings and limited experimental and observational
      data. However, few species have been studied in detail. We describe the
      underwater behavior of a Baird's beaked whale (Berardius bairdii) from the first
      deployment of a multi-sensor acoustic tag on this species. The animal exhibited
      shallow (23 +/- 15 m max depth), intermediate (324 +/- 49 m), and deep (1138 +/-
      243 m) dives. Echolocation clicks were produced with a mean inter-click interval
      of approximately 300 ms and peak frequency of 25 kHz. Two deep dives included
      presumed foraging behavior, with echolocation pulsed sounds (presumed prey
      capture attempts) associated with increased maneuvering, and sustained inverted
      swimming during the bottom phase of the dive. A controlled exposure to simulated
      mid-frequency active sonar (3.5-4 kHz) was conducted 4 hours after tag
      deployment, and within 3 minutes of exposure onset, the tagged whale increased
      swim speed and body movement, and continued to show unusual dive behavior for
      each of its next three dives, one of each type. These are the first data on the
      acoustic foraging behavior in this largest beaked whale species, and the first
      experimental demonstration of a response to simulated sonar.

PMID- 25391310
TI  - Toxicity of hydroxyurea in rats and dogs.
AB  - The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell
      disease, polycythemia, and thrombocytosis that kills cells in mitosis, was
      assessed in repeat-dose, oral gavage studies in rats and dogs and a
      cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic,
      lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response
      curves. In rats dosed for 10 days, 50 mg/kg/day was tolerated; 500 mg/kg/day
      produced decreased body weight gain; decreased circulating leukocytes,
      erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and
      bone marrow; and epithelial degeneration and/or dysplasia of the stomach and
      small intestine; 1,500 mg/kg/day resulted in deaths on day 5. In dogs, a single
      dose at >= 250 mg/kg caused prostration leading to unscheduled euthanasia. Dogs
      administered 50 mg/kg/day for 1 month had decreased circulating leukocytes,
      erythrocytes, and platelets; increased bone marrow cellularity with decreased
      maturing granulocytes; increased creatinine kinase activity; and increased iron
      pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses
      >= 15 mg/kg decreased systolic blood pressure (BP); 50 mg/kg increased diastolic
      BP, heart rate, and change in blood pressure over time (+dP/dt), and decreased QT
      and PR intervals and maximum left ventricular systolic and end diastolic
      pressures with measures returning to control levels within 24 hr.

PMID- 25391311
TI  - Artifactual Stratum Corneum Calcification of the Beagle Dog Tongue.
AB  - Examination of H&E-stained tongue samples from a 26-week intravenous infusion
      study of Beagle dogs, utilizing a compound with no recognized effect on mineral
      metabolism, exhibited superficial stratum corneum calcification in both treated
      and control animals. This resulted in the search for possible causes of the
      finding to help clarify confounding issues. Retrospective examination of 11
      studies performed before the signal case indicated that the problem existed in
      the testing facility but was not recognized. Prior to 2008, this finding was not
      observed, perhaps indicating the requirement for a change in procedures or
      suppliers. Based on the hypothesis that the calcium salts were deposited from
      bone during processing, a series of tests was performed by fixing tongue and
      femur along with different tissues, processed routinely to slide, and stained
      with H&E and von Kossa stains. We conclude that the presence of superficial
      stratum corneum calcification of the tongue in dogs demonstrated in toxicology
      studies is an artifactual change related to the processing of tissues,
      specifically the fixation of tongue in the same container as bone and stomach.
      This change should not be confused with compound-related effects, even when the
      incidence varies between controls and treated animals. 

PMID- 25391312
TI  - Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week
      Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at
      Maximum Tolerated Dose (MTD) in Future Studies.
AB  - High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum
      tolerated dose (MTD), although this dose selection strategy has not been
      critically evaluated. We analyzed the body weight gains (BWGs), mortality, and
      tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at
      BioReliance. Based on our analysis, it is evident that the MTD was exceeded at
      the high and/or mid-doses in several studies. The incidence of tumors in high
      doses was lower when compared to the low and mid-doses of both sexes. Thus, we
      recommend that the high dose in male mice should not exceed one-half of the
      estimated MTD (EMTD), as it is currently chosen, and the next dose should be one
      fourth of the EMTD. Because females were less sensitive to decrements in BWG, the
      high dose in female mice should not exceed two-third of EMTD and the next dose
      group should be one-third of EMTD. If needed, a third dose group should be set at
      one-eighth EMTD in males and one-sixth EMTD in females. In addition, for
      compounds that do not show toxicity in the range finding studies, a limit dose
      should be applied for the 26-week carcinogenicity studies. 

PMID- 25391313
TI  - Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.
AB  - Intradermal delivery of vaccines has been shown to result in dose sparing. We
      tested the ability of fractional doses of inactivated poliovirus vaccine (IPV)
      delivered intradermally to induce levels of serum poliovirus-neutralizing
      antibodies similar to immunization through the intramuscular route.
      Immunogenicity of fractional doses of IPV was studied by comparing intramuscular
      and intradermal immunization of Wistar rats using NanoPass MicronJet600
      microneedles. Intradermal delivery of partial vaccine doses induced antibodies at
      titers comparable to those after immunization with full human dose delivered
      intramuscularly. The results suggest that intradermal delivery of IPV may lead to
      dose-sparing effect and reduction of the vaccination cost. 

PMID- 25391314
TI  - Genetic and epidemiological insights into the emergence of peste des petits
      ruminants virus (PPRV) across Asia and Africa.
AB  - Small ruminants are important components in the livelihood of millions of
      households in many parts of the world. The spread of the highly contagious peste
      des petits ruminants (PPR) disease, which is caused by an RNA virus, PPRV, across
      Asia and Africa remains a major concern. The present study explored the
      evolutionary and epidemiological dynamics of PPRV through the analyses of partial
      N-gene and F-gene sequences of the virus. All the four previously described PPRV
      lineages (I-IV) diverged from their common ancestor during the late-19(th) to
      early-20(th) century. Among the four lineages, PPRV-IV showed pronounced genetic
      structuring across the region; however, haplotype sharing among the geographic
      regions, together with the presence of multiple genetic clusters within a
      country, indicates the possibility of frequent mobility of the diseased
      individuals across the region. The gradual decline in the effective number of
      infections suggests a limited genetic variation, which could be attributed to the
      effective vaccination that has been practiced since 1990s. However, the movement
      of infected animals across the region likely contributes to the spread of PPRV
      IV. No evidence of positive selection was identified from this study. 

PMID- 25391315
TI  - Thickness sorting of two-dimensional transition metal dichalcogenides via
      copolymer-assisted density gradient ultracentrifugation.
AB  - Two-dimensional transition metal dichalcogenides have emerged as leading
      successors to graphene due to their diverse properties, which depend sensitively
      on sample thickness. Although solution-based exfoliation methods hold promise for
      scalable production of these materials, existing techniques introduce
      irreversible structural defects and/or lack sufficient control over the sample
      thickness. In contrast, previous work on carbon nanotubes and graphene has shown
      that isopycnic density gradient ultracentrifugation can produce structurally and
      electronically monodisperse nanomaterial populations. However, this approach
      cannot be directly applied to transition metal dichalcogenides due to their high
      intrinsic buoyant densities when encapsulated with ionic small molecule
      surfactants. Here, we overcome this limitation and thus demonstrate thickness
      sorting of pristine molybdenum disulfide (MoS2) by employing a block copolymer
      dispersant composed of a central hydrophobic unit flanked by hydrophilic chains
      that effectively reduces the overall buoyant density in aqueous solution. The
      resulting solution-processed monolayer MoS2 samples exhibit strong
      photoluminescence without further chemical treatment. 

PMID- 25391316
TI  - Guidance for reading FDG PET scans in dementia patients.
AB  - 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is a
      powerful method for detection of disease-related impairment of cerebral glucose
      metabolism in neurodegenerative diseases. It is of particular interest for early
      and differential diagnosis of dementia. Reading FDG PET scans requires training
      to recognise deviations from normal functional brain anatomy and its variations.
      This paper provides guidance for displaying FDG PET brain scans in a reproducible
      manner that allows reliable recognition of characteristic disease-related
      metabolic changes. It also describes typical findings in Alzheimer's disease,
      Frontotemporal Dementia and Dementia with Lewy Bodies and possible confounding
      factors, such as vascular changes and brain atrophy. It provides a brief overview
      on findings in other neurodegenerative diseases and addresses the potential and
      limitations of software packages for comparison of individual scans with
      reference data. 

PMID- 25391319
TI  - Cause and risk of catastrophic eruptions in the Japanese Archipelago.
AB  - The Japanese Archipelago is characterized by active volcanism with variable
      eruption styles. The magnitude (M)-frequency relationships of catastrophic
      caldera-forming eruptions (M >= 7) are statistically different from those of
      smaller eruptions (M <= 5.7), suggesting that different mechanisms control these
      eruptions. We also find that volcanoes prone to catastrophic eruptions are
      located in regions of low crustal strain rate (<0.5 * 10(8)/y) and propose, as
      one possible mechanism, that the viscous silicic melts that cause such eruptions
      can be readily segregated from the partially molten lower crust and form a large
      magma reservoir in such a tectonic regime. Finally we show that there is a ~1%
      probability of a catastrophic eruption in the next 100 years based on the
      eruption records for the last 120 ky. More than 110 million people live in an
      area at risk of being covered by tephra >20 cm thick, which would severely
      disrupt every day life, from such an eruption on Kyushu Island, SW Japan. 

PMID- 25391317
TI  - Use of gnotobiotic mice to identify and characterize key microbes responsible for
      the development of the intestinal immune system.
AB  - Symbiosis between intestinal microbiota and the host animal plays an important
      role in the homeostasis of host physiology. Since the first production of germ
      free rodents in 1945, it has become increasingly clear that the intestinal immune
      system and the biochemical characteristics of epithelial cells differ greatly
      between conventional and germ-free rodents. However, questions remain about the
      types of microbes involved and the precise mechanism by which these microbes
      affect the host physiology. Here, we review experiments designed to answer these
      questions with the use of gnotobiotic mice. We have determined suitable
      biochemical and immunological markers for monitoring microbial effects in these
      mice. Using these markers, we have found clear differences in epithelial cell
      glycolipid biosynthesis and intraepithelial lymphocyte dynamics between germ-free
      and conventional mice. Furthermore, we have identified a key microbe that
      activates the mucosal immune system in the small intestine. This indigenous
      bacteria, called segmented filamentous bacteria, is a key symbiont in the host
      microbiota interplay, including Th17 cell-inducing activity. 

PMID- 25391318
TI  - Reminiscence of phospholipase B in Penicillium notatum.
AB  - Since the phospholipase B (PLB) was reported as a deacylase of both lecithin and
      lysolecithin yielding fatty acids and glycerophosphocholine (GPC), there was a
      question as to whether it is a single enzyme or a mixture of a phospholipase A2
      (PLA2) and a lysophospholipase (LPL). We purified the PLB in Penicillium notatum
      and showed that it catalyzed deacylation of sn-1 and sn-2 fatty acids of 1,2
      diacylphospholipids and also sn-1 or sn-2 fatty acids of 1- or 2
      monoacylphospholipids (lysophospholipids). Further, it also has a monoacyllipase
      activity. The purified PLB is a glycoprotein with m.w. of 91,300. The sugar
      moiety is M9 only and the protein moiety consists of 603 amino acids. PLB,
      different from PLA2, shows other enzymatic activities, such as transacylase,
      lipase and acylesterase. PLB activity is influenced by various substances, e.g.
      detergents, deoxycholate, diethylether, Fe(3+), and endogenous protease.
      Therefore, PLB might have broader roles than PLA2 in vivo. The database shows an
      extensive sequence similarity between P. notatum PLB and fungal PLB, cPLA2 and
      patatin, suggesting a homologous relationship. The catalytic triad of cPLA2, Ser,
      Asp and Arg, is also present in P. notatum PLB. Other related PLBs, PLB/Lipases
      are discussed.

PMID- 25391320
TI  - Novel plasma biomarker surrogating cerebral amyloid deposition.
AB  - Alzheimer's disease (AD) is the most common and devastating dementia. Simple and
      practical biomarkers for AD are urgently required for accurate diagnosis and to
      facilitate the development of disease-modifying interventions. The subjects for
      the study were selected on the basis of PiB amyloid imaging by PET. Forty PiB
      positive (PiB+) individuals, including cognitively healthy controls (HC), and
      mild cognitive impairment and AD individuals, and 22 PiB-negative (PiB-) HC
      participated. Employing our novel highly sensitive immunoprecipitation-mass
      spectrometry, we measured plasma amyloid beta-proteins (Abetas; Abeta1-40 and
      Abeta1-42) and Abeta-approximate peptides (AbetaAPs), which were cleaved from
      amyloid precursor protein (APP). Among the AbetaAPs, APP669-711 appeared to be a
      good reference for deciphering pathological change of Abeta1-42. We evaluated the
      performance of the ratio of APP669-711 to Abeta1-42 (APP669-711/Abeta1-42) as a
      biomarker. APP669-711/Abeta1-42 significantly increased in the PiB+ groups. The
      sensitivity and specificity to discriminate PiB+ individuals from PiB-
      individuals were 0.925 and 0.955, respectively. Our plasma biomarker precisely
      surrogates cerebral amyloid deposition. 

PMID- 25391322
TI  - Spin-orbit coupling in surface plasmon scattering by nanostructures.
AB  - The spin Hall effect leads to the separation of electrons with opposite spins in
      different directions perpendicular to the electric current flow because of
      interaction between spin and orbital angular momenta. Similarly, photons with
      opposite spins (different handedness of circular light polarization) may take
      different trajectories when interacting with metasurfaces that break spatial
      inversion symmetry or when the inversion symmetry is broken by the radiation of a
      dipole near an interface. Here we demonstrate a reciprocal effect of spin-orbit
      coupling when the direction of propagation of a surface plasmon wave, which
      intrinsically has unusual transverse spin, determines a scattering direction of
      spin-carrying photons. This spin-orbit coupling effect is an optical analogue of
      the spin injection in solid-state spintronic devices (inverse spin Hall effect)
      and may be important for optical information processing, quantum optical
      technology and topological surface metrology. 

PMID- 25391321
TI  - Ionizing radiation-induced XRCC4 phosphorylation is mediated through ATM in
      addition to DNA-PK.
AB  - XRCC4 (X-ray cross-complementation group 4) is a protein associated with DNA
      ligase IV, which is thought to join two DNA ends at the final step of DNA double
      strand break repair through non-homologous end-joining. It has been shown that,
      in response to irradiation or treatment with DNA damaging agents, XRCC4 undergoes
      phosphorylation, requiring DNA-PK. Here we explored possible role of ATM, which
      is structurally related to DNA-PK, in the regulation of XRCC4. The
      radiosensitizing effects of DNA-PK inhibitor and/or ATM inhibitor were dependent
      on XRCC4. DNA-PK inhibitor and ATM inhibitor did not affect the ionizing
      radiation-induced chromatin recruitment of XRCC4. Ionizing radiation-induced
      phosphorylation of XRCC4 in the chromatin-bound fraction was largely inhibited by
      DNA-PK inhibitor but further diminished by the combination with ATM inhibitor.
      The present results indicated that XRCC4 phosphorylation is mediated through ATM
      as well as DNA-PK, although DNA-PK plays the major role. We would propose a
      possible model that DNA-PK and ATM acts in parallel upstream of XRCC4, regulating
      through phosphorylation. 

PMID- 25391323
TI  - Chiropractic and rehabilitation management of a patient with extraforaminal
      entrapment of L4 nerve with balance problem.
AB  - BACKGROUND: Disc herniation is one of the most common causes of low back pain
      with radicular pain. Among various types of disc herniation, the extraforaminal
      disc herniation is a rare cause of lumbar radiculopathy. The aim of presenting
      this case study is to demonstrate the benefits of Chiropractic care including
      spine and extremity manipulation and rehabilitation in the treatment of a rare
      case of extraforaminal L4 nerve entrapment causing severe L4 radiculopathy and
      chronic mild low back pain (LBP). OBJECTIVE: The aim of presenting this case
      study is to demonstrate the benefits of Chiropractic care including spine and
      extremity manipulation and rehabilitation in treatment of rare case of
      extraforaminal L4 nerve entrapment which caused severe L4 radiculopathy and
      chronic mild low back pain (LBP). METHOD: A 45-year old female patient arrived at
      the clinic with chronic mild low back pain and right buttock pain, all of which
      had presented for two years' duration. During the preceding month, the radicular
      pain initiated in medium to high intensity, radiating to her right leg following
      the L4 dermatomal pattern with a periodic tingling sensation in her right foot. A
      neuro exam demonstrated a proprioception deficit in her right leg. A Romberg test
      was positive. The patient was treated by low amplitude high velocity spinal and
      extremity manipulation for 10 consecutive sessions (2 weeks), followed by
      rehabilitation and exercise therapy including advanced myofascial release therapy
      for an additional 12 sessions (4 weeks). RESULTS: After treatment, the patient
      reported a significant improvement in her low back pain and radiculopathy. In
      addition, she achieved some improvement in balance. CONCLUSION: It seems that
      Chiropractic care and rehabilitation therapy may be a safe and effective modality
      in treatment of an L4 radiculopathy in a patient with an extraforaminal L4 nerve
      entrapment. Although it is rare, an L4 extraforaminal disc herniation should be
      considered as a possible cause of symptoms in patients with chronic mild low back
      pain and severe L4 radiculopathy.

PMID- 25391324
TI  - Effects of bridge exercises with a sling and vibrations on abdominal muscle
      thickness in healthy adults.
AB  - In the present study, we aimed to examine the changes in the thickness of the
      transversus abdominis (TrA) and internal oblique (Io) muscles using
      ultrasonography in adults who performed bridge exercises with the abdominal
      drawing-in maneuver and a sling and received micro vibrations. In total, 32
      subjects were divided into a therapy (n= 16) and control (n= 16) groups. The
      therapy group completed nine sets, with four repetitions, of bridge exercises
      with the sling and received vibrations. The control group completed nine sets,
      with four repetitions, of bridge exercises with the sling and did not receive
      vibrations. The thicknesses of the TrA and Io muscles were measured in both
      groups using ultrasonography before and after therapy. According to the pressure
      applied to the biofeedback unit, both groups showed significant changes in the
      thicknesses of the TrA and Io muscles after therapy (P< 0.05). The change in the
      thickness of the TrA muscle after therapy was significantly different between the
      2 groups when the pressures applied at 38, 42, and 46 mmHg (P< 0.05). Moreover,
      the change in the thickness of the Io muscle did not significantly different
      between the 2 groups at any of the pressures applied (P> 0.05). These findings
      indicate that approximately 15 minutes of vibrations during bridge exercises on
      unstable surfaces with a sling facilitates the activation of the deep trunk
      muscles and further enhances the activation of the TrA. 

PMID- 25391325
TI  - Age-related progressive increase of lower back pain among male dance sport
      competitors.
AB  - BACKGROUND: Occurrence of musculoskeletal pain in dance sport dancers is often a
      cause for longer discontinuation of training, which affects the competition
      results. OBJECTIVE: The aim of the research project was to determine the age
      specific pain experience among male dance sport competitors by defining the
      proportions of pain status of fourteen body regions. METHODS: The subject sample
      of 200 male dancers from 44 different countries and with international
      competitive experience was divided into three subsamples according to age. Three
      online questionnaires translated into eight world languages were used for data
      collection: (1) basic data questionnaire, (2) self-estimated functional inability
      because of pain questionnaire designed for dancers, and (3) health care-related
      questionnaire. RESULTS: After examining the 14 topological regions, it was
      established that dancers most often report pain in the lower back region (53.5%),
      followed by knee (43%) and toe regions (40.5%). Significant differences were
      found using the Chi-square test between the groups of dancers of different ages
      in the prevalence of pain in the lower back (chi 2 = 12.6), shoulders (chi 2 =
      9.7), and hip region (chi 2 = 7), with the highest, age-related progressive
      differences in the lower back region (36.2-54.9-63.4%) so older dancers had more
      pain. Often reported reasons for discontinuation of training increased with age
      are overuse syndrome/tendinitis (6.4-15.9-22.5%) and strain (14.9-29.3-31%). Most
      common causes for longer discontinuation of training are absence of partner
      (37%), injuries (24%), and overuse syndrome (10%). CONCLUSION: Lower back pain is
      propounding health problem in male dancers and increases with age that cannot be
      resolved by decreasing training intensity. This research reveals that only 28% of
      male dancers will seek medical help because of occurrence of musculoskeletal
      pain. Multidisciplinary approach with the aim of long-term health protection and
      prolongation of dancing careers is required in future studies.

PMID- 25391326
TI  - Effect of a multidisciplinary program for the prevention of low back pain in
      hospital employees: a randomized controlled trial.
AB  - BACKGROUND: Hospital workers with physically demanding jobs are at risk for
      developing recurrent LBP. There is a lack of studies evaluating multidisciplinary
      prevention of low back pain (LBP) in hospital workers. OBJECTIVE: This randomized
      controlled trial evaluates the effect of a multidisciplinary prevention program,
      focusing on a client-centred approach, on hospital workers at risk for developing
      LBP. METHODS: Caregiving hospital workers were allocated to an experimental (12
      week lasting multidisciplinary prevention program) or control group (no
      intervention). They were evaluated prior to the intervention and after a 6 months
      follow-up period. Primary outcome measures included incidence of LBP, work
      absenteeism and general health. Secondary outcomes included daily physical
      activity, job satisfaction and coping strategies. RESULTS: A significant
      improvement was seen for passive coping after 6 months follow-up, but no
      significant differences were observed between groups in primary or other
      secondary outcome measures (p> 0.05). CONCLUSIONS: A multidisciplinary prevention
      program fitting into a bio-psychosocial context may not have been intensive
      enough to promote a change in daily habitudes, and had no effect on work
      absenteeism, incidence of LBP or general health. Further research should
      determine whether prevention of LBP is possible in caregiving personnel.

PMID- 25391327
TI  - Pharmacological, psychological, and patient education interventions for patients
      with neck pain: results of an international survey.
AB  - BACKGROUND: Examination of practice patterns compared to existing evidence
      identifies knowledge to practice gaps. OBJECTIVES: To describe the utilization of
      pharmacological, patient education, primary psychological interventions and
      relaxation therapies in patients with neck pain by clinicians. METHODS: An
      international cross-sectional survey was conducted to determine the use of these
      interventions amongst 326 clinicians treating patients with neck pain. RESULTS:
      Nineteen countries participated. Results were analyzed by usage amongst physical
      therapists (39%) and chiropractors (35%), as they were the predominant
      respondents. Patient education (95%) and relaxation therapies (59%) were the most
      utilized interventions. Tests of subgroup differences determined that physical
      therapists used patient education significantly more than chiropractors. Use of
      medications and primary psychological interventions were reported by most to be
      outside of scope of practice. The high rate of patient education is consistent
      with supporting evidence. However, usage of relaxation therapies is contrary to
      evidence suggesting no benefit for improved pain or function for chronic neck
      pain. CONCLUSION: This survey indicates that patient education and relaxation
      therapies are common treatments provided by chiropractors and physical therapists
      for patients with neck pain. Future research should address gaps associated with
      variable practice patterns and knowledge translation to reduce usage of
      interventions shown to be ineffective.

PMID- 25391328
TI  - Ultrasound assessment of trunk muscles and back flexibility, strength and
      endurance in off-road cyclists with and without low back pain.
AB  - OBJECTIVES: To compare the thickness of lateral abdominal muscles and Cross
      Sectional Area (CSA) of lumbar Multifidus Spinae (LM) muscles of competitive off
      road cyclists with and without Low Back Pain (LBP). We also aimed to compare the
      maximum isometric back strength and endurance, as well as flexibility of lower
      back in cyclists with LBP and in the controls. METHODS: The thickness of
      Transversus Abdominis (TrA), Internal Oblique (IO) and External Oblique (EO)
      along with the CSA of LM muscles of 14 professional competitive off-road cyclists
      with LBP and 24 controls were measured by ultrasound (US) in hook-lying position
      on the examination table, and mounted on the bicycle. In addition, the back
      strength and endurance of the subjects and the flexibility of the participants
      were measured. RESULTS: Data showed a significantly lower thickness of
      Transversus Abdominis (TrA) and CSA of LM muscles in cyclists with LBP comparing
      to controls in all positions. No significant result regarding the flexibility of
      the subjects in case group comparing with the controls was found (p= 0.674). In
      addition, it was found that there is no significant difference in isometric back
      strength of the subjects between the groups (p= 0.105). However, we found that
      subjects with LBP have a lower endurance in back dynamometry with 50% of their
      maximum isometric back strength (p= 0.016). CONCLUSION: In this study, useful
      information regarding possible factors associated with low back pain in off- road
      cyclists was found (lower thickness of TrA and LM muscles and decreased back
      endurance).

PMID- 25391329
TI  - A brief intervention utilising visual feedback reduces pain and enhances tactile
      acuity in CLBP patients.
AB  - BACKGROUND: Chronic low back pain (CLBP) is a serious health problem in
      industrialised countries and the efficacy of current treatment options is
      unsatisfying. OBJECTIVE: The present study examines the effects of a combined
      intervention that utilizes visual feedback, motion and sensory discrimination
      training in CLBP patients. METHODS: Thirty patients of an outpatient orthopaedic
      rehabilitation unit were randomly assigned to either feedback or control group.
      In addition to standard treatment, patients of the feedback group received 6
      feedback sessions where they watched the image of their back during a brief 2
      point discrimination training and, after that, while they were tilting their
      pelvis up and down on the left and right side using their lumbar musculus
      multifidus solely. The control group received 6 sessions consisting of 2 units of
      physiotherapy, relaxation training and movement training (walking) each. RESULTS:
      A significant effect on self-reported pain and sensory discrimination threshold
      could be found for the feedback intervention, while, as expected, other pain
      related variables, like pain anxiety, pain vigilance, depression and cognitive
      appraisal of pain remained unchanged. CONCLUSIONS: These findings imply that very
      simple feedback interventions without major technical requirements could be a
      valuable supplement to standard treatment in CLBP.

PMID- 25391330
TI  - Genetic skeletal dysplasias: a guide to diagnosis and management.
AB  - The skeletal dysplasias are a large, heterogeneous group of genetic disorders
      characterised by abnormal growth, development and remodelling of the bones and
      cartilage that comprise the human skeleton. They typically present with
      disproportionate short stature in childhood, or premature osteoarthritis in
      adulthood. The latest classification lists 456 disorders under 40 group headings
      differentiated by specific clinical, radiographic and molecular criteria.
      Establishing an accurate diagnosis is important to predict final height, expected
      complications and treatment, and for specific genetic and psychological
      counselling. In addition to the skeletal disorder, individuals frequently
      demonstrate abnormalities of hearing, vision, neurological, pulmonary, renal or
      cardiac function that require multidisciplinary assessment. This review provides
      a guide to diagnosis and discusses management principles for the common limb and
      spinal abnormalities that affect quality of life for the majority. 

PMID- 25391332
TI  - Preparation and characterization of mucoadhesive nanoparticles of poly (methyl
      vinyl ether-co-maleic anhydride) containing glycyrrhizic acid intended for
      vaginal administration.
AB  - Traditional vaginal preparations reside in the vaginal cavity for relatively a
      short period of time, requiring multiple doses in order to attain the desired
      therapeutic effect. Therefore, mucoadhesive systems appear to be appropriate to
      prolong the residence time in the vaginal cavity. In the current study,
      mucoadhesive nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride)
      (PVM/MA) intended for vaginal delivery of glycyrrhizic acid (GA) (a drug with
      well-known antiviral properties) were prepared and characterized. Nanoparticles
      were generated by a solvent displacement method. Incorporation of GA was
      performed during nanoprecipitation, followed by adsorption of drug once
      nanoparticles were formed. The prepared nanoparticles were characterized in terms
      of size, Z-potential, morphology, drug loading, interaction of GA with PVM/MA (by
      differential scanning calorimetry) and the in vitro interaction of nanoparticles
      with pig mucin (at two pH values, 3.6 and 5; with and without GA adsorbed). The
      preparation method led to nanoparticles of a mean diameter of 198.5 +/- 24.3 nm,
      zeta potential of -44.8 +/- 2.8 mV and drug loading of 15.07 +/- 0.86 ug/mg
      polymer. The highest mucin interaction resulted at pH 3.6 for nanoparticles
      without GA adsorbed. The data obtained suggest the promise of using mucoadhesive
      nanoparticles of PVM/MA for intravaginal delivery of GA. 

PMID- 25391333
TI  - Cross-sector, sessional employment of pharmacists in rural hospitals in Australia
      and New Zealand: a qualitative study exploring pharmacists' perceptions and
      experiences.
AB  - BACKGROUND: Many rural hospitals in Australia and New Zealand do not have an on
      site pharmacist. Sessional employment of a local pharmacist offers a potential
      solution to address the clinical service needs of non-pharmacist rural hospitals.
      This study explored sessional service models involving pharmacists and factors
      (enablers and challenges) impacting on these models, with a view to informing
      future sessional employment. METHODS: A series of semi-structured one-on-one
      interviews was conducted with rural pharmacists with experience, or intention to
      practise, in a sessional employment role in Australia and New Zealand.
      Participants were identified via relevant newsletters, discussion forums and
      referrals from contacts. Interviews were conducted during August 2012-January
      2013 via telephone or SkypeTM, for approximately 40-55 minutes each, and
      recorded. RESULTS: Seventeen pharmacists were interviewed: eight with ongoing
      sessional roles, five with sessional experience, and four working towards
      sessional employment. Most participants provided sessional hospital services on a
      weekly basis, mainly focusing on inpatient medication review and consultation.
      Recognition of the value of pharmacists' involvement and engagement with other
      healthcare providers facilitated establishment and continuity of sessional
      services. Funds pooled from various sources supplemented some pharmacists'
      remuneration in the absence of designated government funding. Enhanced employment
      opportunities, district support and flexibility in services facilitated the
      continuous operation of the sessional service. CONCLUSIONS: There is potential to
      address clinical pharmacy service needs in rural hospitals by cross-sector
      employment of pharmacists. The reported sessional model arrangements, factors
      impacting on sessional employment of pharmacists and learnings shared by the
      participants should assist development of similar models in other rural
      communities.

PMID- 25391334
TI  - Effects of pesticide chemicals on the activity of metabolic enzymes: focus on
      thiocarbamates.
AB  - INTRODUCTION: Thiocarbamates are chemicals widely used as pesticides.
      Occupational exposure is associated with acute intoxication. Populations can be
      exposed through food and water. Moreover, certain thiocarbamates are used
      clinically. The widespread use of thiocarbamates raises many issues regarding
      their toxicological and pharmacological impact. AREAS COVERED: Thiocarbamates and
      their metabolites can modify biological macromolecules functions, in particular
      enzymes, through modification of cysteine residues, chelation of metal ions or
      modulation of the oxidative stress. Loss of enzyme activity can lead to the
      disruption of metabolic pathways, and explain, at least in part, the effects of
      these pesticides. Additionally, their reactivity and ability to easily cross
      biological barrier confer them a great interest for development of clinical
      applications. EXPERT OPINION: Many advances in the study of thiocarbamates
      metabolism and reactivity have led to a better knowledge of biological effects of
      these compounds. However, more data are needed on the determination of targets
      and specificity. Only few data concerning the exposure to a cocktail of
      pesticides/chemicals are available, raising the need to evaluate the toxic side
      effects of representative pesticides mixtures. Moreover, the dithiocarbamate
      Disulfiram has shown great potential in therapeutic applications and leads to the
      development of pharmacological thiocarbamates derivatives, highly specific to
      their target and easily distributed.

PMID- 25391335
TI  - Direct detection of DNA below ppb level based on thionin-functionalized layered
      MoS2 electrochemical sensors.
AB  - A layered MoS2-thionin composite was prepared by sonicating their mixture in an
      ionic liquid and gradient centrifugation. Because DNA is rarely present in single
      stranded form, either naturally or after PCR amplification, the composite was
      used for fabrication of a double-stranded DNA (dsDNA) electrochemical biosensor
      due to stable electrochemical response, intercalation, and electrostatic
      interaction of thionin with DNA. The linear range over dsDNA concentration from
      0.09 ng mL(-1) to 1.9 ng mL(-1) is obtained, and moreover, it is suitable for the
      detection of single-stranded DNA (ssDNA). The biosensor has been applied to the
      detection of circulating DNA from healthy human serum, and satisfactory results
      have been obtained. The constructed DNA electrochemical biosensor shows potential
      application in the fields of bioanalysis and clinic diagnosis. Furthermore, this
      work proposes a new method to construct electrochemical biosensors based on MoS2
      sheets. 

PMID- 25391336
TI  - Neuropsychological outcome after endoscopic third ventriculostomy.
AB  - BACKGROUND: Cognitive dysfunction is a common complaint associated with
      obstructive hydrocephalus. The purpose of this study was to determine the effect
      of endoscopic third ventriculostomy (ETV) on the neuropsychological outcome in
      patients presenting with cognitive decline and obstructive hydrocephalus.
      METHODS: A retrospective review of patients who underwent ETV at the University
      of Calgary and had both pre and post operative neuropsychological testing, was
      completed. Presenting clinical features, etiology of hydrocephalus and ventricle
      size utilizing frontal occipital horn ratio was obtained. Outcomes and
      complications of the ETV were recorded. Detailed measures of intelligence,
      attention and concentration, executive function, visual and verbal memory,
      language functions and fine motor skills were completed. Post treatment change
      was determined utilizing Reliable Change Index. RESULTS: A total of 13 patients
      were identified. Etiology of the hydrocephalus was aqueductal stenosis in 8 and
      tectal glioma in 4. The majority of patients (11 of 13, 85%) demonstrated
      cognitive dysfunction at the borderline (<=1 SD) or impairment level (<=1.5 SDs)
      in at least one domain. Nine patients (69%) showed reliable improvement in at
      least one cognitive domain. The greatest improvement was seen with visual memory
      (42%). One quarter to one third of patients demonstrated improvement on tests of
      intelligence quotient, verbal memory, attention and concentration, and executive
      function. Two patients declined in executive functioning. Ventricle size improved
      in eight patients. CONCLUSIONS: ETV is a safe effective procedure, capable of
      producing reliable improvements in cognitive dysfunction with hydrocephalus.
      Patients with cognitive complaints alone may benefit from ETV.

PMID- 25391337
TI  - [Validity of the suicidality assessment instrument PRISM-S (Pictoral
      Representation of Illness Self Measure - Suicidality)].
AB  - In routine clinical practice the assessment of suicidality proves to be difficult
      and complex. The aim of the present study was to examine if PRISM can be used to
      measure validly the person's subjectively perceived suicidality. The nonverbal
      visualization technique PRISM (Pictoral Representation of Illness and Self
      Measure) has been developed by Buchi et al. (2002) to evaluate the perceived
      burden of suffering due to physical illness. The adapted version of PRISM used in
      our study is called PRISM-S (Pictoral Representation of Illness and Self Measure 
      Suicidality). 156 eligible inpatients, admitted voluntarily to the crisis
      intervention centre Winterthur, participated in the study. We used as gold
      standards the well established assessment tools the Beck Scale of Suicide
      Ideation (BSS) and the Depressive Symptome Inventory - Subscale (DSI-SS). The
      results showed high correlations between PRISM-S and the BSS (r = - 0,73) and the
      DSI-SS scores (r = - 0,76). Clinicians, general practitioners, psychiatrists and
      psychologists receive with PRISM-S a valid suicidality assessment tool that is
      very brief and easy to administer in clinical settings.

PMID- 25391340
TI  - IOF Taipei final programme.

PMID- 25391341
TI  - IOF Regionals - 5(th) Asia-Pacific Osteoporosis Meeting : Plenary Lectures.

PMID- 25391338
TI  - CryptoDex: a randomised, double-blind, placebo-controlled phase III trial of
      adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis:
      study protocol for a randomised control trial.
AB  - BACKGROUND: Cryptococcal meningitis (CM) is a severe AIDS-defining illness with
      90-day case mortality as high as 70% in sub-Saharan Africa, despite treatment. It
      is the leading cause of death in HIV patients in Asia and Africa.No major advance
      has been made in the treatment of CM since the 1970s. The mainstays of induction
      therapy are amphotericin B and flucytosine, but these are often poorly available
      where the disease burden is highest. Adjunctive treatments, such as
      dexamethasone, have had dramatic effects on mortality in other neurologic
      infections, but are untested in CM. Given the high death rates in patients
      receiving current optimal treatment, and the lack of new agents on the horizon,
      adjuvant treatments, which offer the potential to reduce mortality in CM, should
      be tested.The principal research question posed by this study is as follows: does
      adding dexamethasone to standard antifungal therapy for CM reduce mortality?
      Dexamethasone is a cheap, readily available, and practicable intervention.
      METHOD: A double-blind placebo-controlled trial with parallel arms in which
      patients are randomised to receive either dexamethasone or placebo, in addition
      to local standard of care. The study recruits patients in both Asia and Africa to
      ensure the relevance of its results to the populations in which the disease
      burden is highest. The 10-week mortality risk in the control group is expected to
      be between 30% and 50%, depending on location, and the target hazard ratio of 0.7
      corresponds to absolute risk reductions in mortality from 30% to 22%, or from 50%
      to 38%. Assuming an overall 10-week mortality of at least 30% in our study
      population, recruitment of 824 patients will be sufficient to observe the
      expected number of deaths. Allowing for some loss to follow-up, the total sample
      size for this study is 880 patients. To generate robust evidence across both
      continents, we aim to recruit roughly similar numbers of patients from each
      continent. The primary end point is 10-week mortality. Ethical approval has been
      obtained from Oxford University's Tropical Research Ethics Committee (OxTREC),
      and as locally mandated at each site. TRIAL REGISTRATION: International Standard
      Randomised Controlled Trial Number: ISRCTN59144167 26-July-2012.

PMID- 25391339
TI  - Characterizing the interaction between DNA and GelRed fluorescent stain.
AB  - We have performed single-molecule stretching and dynamic light-scattering (DLS)
      experiments to characterize the interaction between the DNA molecule and the
      fluorescent stain GelRed. The results from single-molecule stretching show that
      the persistence length of DNA-GelRed complexes increases as the ligand
      concentration increases up to a critical concentration, then decreases for higher
      concentrations. The contour length of the complexes, on the other hand, increases
      monotonically as a function of GelRed concentration, suggesting that
      intercalation is the main binding mechanism. To characterize the physical
      chemistry of the interaction, we used the McGhee-von Hippel binding isotherm to
      extract physicochemical data for the interaction from the contour length data.
      Such analysis enabled us to conclude that the GelRed stain is, in fact, a bis
      intercalator. In addition, DLS experiments were performed to study the changes of
      the effective size of the DNA-GelRed complexes, measured as the hydrodynamic
      radius, as a function of ligand concentration. We observed qualitative agreement
      between the results obtained from the two techniques by comparing the behavior of
      the hydrodynamics radius and the radius of gyration, because the latter quantity
      can be expressed as a function of mechanical properties determined from the
      stretching experiments. 

PMID- 25391342
TI  - IOF Regionals - 5(th) Asia-Pacific Osteoporosis Meeting : Oral Communications.

PMID- 25391343
TI  - IOF Regionals - 5(th) Asia-Pacific Osteoporosis Meeting : Poster Presentations.

PMID- 25391345
TI  - Prebiotics and probiotics in irritable bowel syndrome and inflammatory bowel
      disease in children.
AB  - Underlying pathophysiological mechanisms of irritable bowel syndrome (IBS), a
      common disorder characterized by abdominal pain associated to a change in stool
      consistency or frequency, include low-grade inflammation and intestinal
      microbiota changes. Few and disappointing data are available for prebiotics. A
      few controlled trials (RCTs) of probiotics are instead available with favourable
      effects, although most are limited by suboptimal design and small sample size. A
      recent report from the Rome foundation group included 32 RCTs of probiotics, most
      of which showed an overall modest improvement in symptoms, with the patients most
      benefitting from probiotics being those with predominant diarrhoea and those
      having a post-infectious IBS. A review focusing only on children with functional
      gastrointestinal disorders concluded that probiotics are more effective than
      placebo in the treatment of patients with abdominal pain-related functional
      gastrointestinal disorders, although no effect on constipation was evident. The
      role for probiotics in inflammatory bowel disease (IBD) appears logical: the
      endogenous intestinal microbiota plays a central role in their development, and
      various probiotics have been found effective in animal models of IBD. However,
      research in humans has been overall quite limited, and it would seem that after a
      phase of intense research in the first decade of this century, the pace has
      slowed down, with fewer clinical trials been published in the past 2-3 years. To
      summarize current evidence: no probiotic has proven successful in Crohn's
      disease. In ulcerative colitis, on the other hand, data are more promising, and a
      very recent meta-analysis, that included 23 randomized controlled trials,
      concluded that there is evidence of efficacy for the probiotic mixture VSL#3 in
      helping inducing and maintaining remission, as well as in maintaining remission
      in patients with pouchitis. It is fair to state that for both IBD and IBS, more
      well-designed, rigorous, randomized clinical trials must be performed. 

PMID- 25391346
TI  - Bifidobacterium longum subsp. infantis BB-02 attenuates acute murine experimental
      model of inflammatory bowel disease.
AB  - Inflammatory bowel diseases (IBD) are chronic inflammatory conditions,
      characterised by remissions and relapses episodes, whose main manifestations are
      ulcerative colitis and Crohn's disease. Ulcerative colitis (UC), one of the main
      forms of IBD, has as standard treatment the use of corticosteroids and anti
      inflammatory drugs. The use of antibiotics has been also reported, but the
      possible adverse effects, such as disturbance of the indigenous microbiota or
      resistance induction, should be taken into consideration, and thus the use of
      probiotics emerges as a possible alternative option of treatment. In this study,
      the oral administration of Bifidobacterium longum subsp. infantis BB-02 was
      evaluated as a preventive strategy for acute experimental UC induced in female
      BALB/c mice by ingestion of 3.5% dextran sulphate sodium in drinking water during
      7 days. During this time, the daily disease activity index was evaluated, and on
      the seventh day the animals were euthanised to collect intestines and liver for
      analysis. Treatment with the probiotic resulted in clinical improvement of the
      animals. The histological and morphometric analyses showed a reduction of lesions
      and oedema in the gut, but there was no increase in the production of mucin. The
      dosage of secretory immunoglobulin A was significantly higher in the colitis
      group and reduced in the group treated with the probiotic. There was also a
      reduction in the inflammation of the colon, as demonstrated by a decrease in
      neutrophils infiltration, and KC/CXCL-1 levels. The intestinal permeability,
      which is typically increased during the onset of IBD, was also reduced by
      treatment with probiotic. Based on these data, it can be concluded that the
      bacterium B. infantis BB-02 has a probiotic potential for the attenuation of UC,
      but further studies should be conducted to verify the mechanism of protective
      action of the bacterium. 

PMID- 25391347
TI  - Role of anaerobic fungi in wheat straw degradation and effects of plant feed
      additives on rumen fermentation parameters in vitro.
AB  - In the present study, rumen microbial groups, i.e. total rumen microbes (TRM),
      total anaerobic fungi (TAF), avicel enriched bacteria (AEB) and neutral detergent
      fibre enriched bacteria (NEB) were evaluated for wheat straw (WS) degradability
      and different fermentation parameters in vitro. Highest WS degradation was shown
      for TRM, followed by TAF, NEB and least by AEB. Similar patterns were observed
      with total gas production and short chain fatty acid profiles. Overall, TAF
      emerged as the most potent individual microbial group. In order to enhance the
      fibrolytic and rumen fermentation potential of TAF, we evaluated 18 plant feed
      additives in vitro. Among these, six plant additives namely Albizia lebbeck,
      Alstonia scholaris, Bacopa monnieri, Lawsonia inermis, Psidium guajava and
      Terminalia arjuna considerably improved WS degradation by TAF. Further evaluation
      showed A. lebbeck as best feed additive. The study revealed that TAF plays a
      significant role in WS degradation and their fibrolytic activities can be
      improved by inclusion of A. lebbeck in fermentation medium. Further studies are
      warranted to elucidate its active constituents, effect on fungal population and
      in vivo potential in animal system. 

PMID- 25391348
TI  - The role of probiotics and prebiotics in the prevention of infections in child
      day-care centres.
AB  - Infants and children attending day-care centres demonstrate a notably higher risk
      of gastrointestinal as well as of respiratory tract infections. The present short
      review evaluates various well-controlled clinical trials analysing the effect of
      probiotics and prebiotics in the prevention of such infections. In most of the 12
      studies identified, probiotic supplementation was found to be a safe and
      effective therapeutic tool in preventing gastrointestinal and respiratory
      infection in this population. 

PMID- 25391349
TI  - Human intestinal mucosa-associated Lactobacillus and Bifidobacterium strains with
      probiotic properties modulate IL-10, IL-6 and IL-12 gene expression in THP-1
      cells.
AB  - Lactobacilli and bifidobacteria are considered one of the permanent genera of the
      physiological human intestinal microbiota and represent an enormous pool of
      potential probiotic candidates. Approximately 450 isolates of presumptive
      Lactobacillus or Bifidobacterium strains were obtained from bioptic samples of
      colonic and ileal mucosa from 15 adolescents aged 12 to 18 years. On the basis of
      randomly amplified polymorphic DNA (RAPD)-PCR analysis, 20 strains were selected
      for further taxonomic classification and characterisation, as well as assessment
      of probiotic properties and safety. Importantly, selected strains showed the
      capability of colonising different parts of the intestine. The most frequently
      isolated species was Lactobacillus paracasei followed by Lactobacillus fermentum.
      The majority of isolates were susceptible to antimicrobials of human and
      veterinary importance, however, tetracycline and/or erythromycin resistance was
      observed in Lactobacillus plantarum and L. fermentum strains. Thirteen strains
      were able to ferment more than 19 different carbon sources and three out of five
      tested strains exerted antagonistic activity against several different indicator
      strains. Two Lactobacillus isolates (L. paracasei L350 and L. fermentum L930 bb)
      and one Bifidobacterium isolate (Bifidobacterium animalis subsp. animalis IM386)
      fulfilled in vitro selection criteria for probiotic strains and exhibited strong
      downregulation of pro-inflammatory cytokines IL-6 and IL-12 and upregulation of
      anti-inflammatory IL-10. The selected strains represent suitable candidates for
      further studies regarding their positive influence on host health and could play
      an important role in ameliorating the symptoms of inflammatory bowel diseases. 

PMID- 25391350
TI  - Cardiohepatic syndrome.
AB  - Accumulating evidence shows that acute as well as chronic heart disease can
      directly contribute to an acute or chronic worsening of liver function and vice
      versa. Description and definition of cardiohepatic syndrome (CHS) in this review
      are based on the cardiorenal syndrome (CRS) concept. The eye-catching analogy
      between CHS and CRS is applied to facilitate an understanding of the
      pathophysiology and overall burden of disease for each of the proposed CHS
      subtypes, their natural course, and associated morbidity and mortality. 

PMID- 25391351
TI  - Therapeutic adjustments in stage D heart failure: challenges and strategies.
AB  - The morbidity and mortality associated with heart failure (HF) represents a
      significant public health challenge. Stage D HF identifies a distinct subgroup of
      advanced HF patients characterized by adverse clinical and hemodynamic factors
      which warrant evaluation for specialized advanced management strategies and/or
      consideration of palliative care in tandem with the same recommendations for goal
      directed optimal medical therapy as earlier stages of HF. In fact, one of the
      inherent markers of progression to stage D disease is the need to withdraw
      previously tolerated neurohormonal agents in the setting of systemic circulatory
      limitations or renal dysfunction. Furthermore, the requirement for aggressive
      diuresis in the setting of borderline blood pressures and renal insufficiency is
      often complicated by worsening renal impairment. Assessment of the appropriate
      need for inotropic support, given the significant complications associated with
      their use, is also a frequently encountered challenge complicating the medical
      management of Stage D HF. This review outlines some of the most relevant
      challenges of pharmacological therapy in stage D HF and describes current and
      future strategies that may be employed to overcome some of these obstacles. 

PMID- 25391352
TI  - Rhizobium pakistanensis sp. nov., isolated from groundnut (Arachis hypogaea)
      nodules grown in rainfed Pothwar, Pakistan.
AB  - A Gram-negative, white, non-motile, rod shaped bacterial strain BN-19(T) was
      isolated from a root nodule of groundnut (Arachis hypogaea) in Pakistan.
      Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain BN
      19(T) formed a subclade in the genus Rhizobium together with Rhizobium alkalisoli
      CCBAU 01393(T), Rhizobium vignae CCBAU 05176(T), Rhizobium huautlense SO2(T) and
      Rhizobium tarimense PL-41(T) with sequence similarities of 97.5, 97.3, 97.2 and
      97.1 % respectively. Sequence analysis of housekeeping genes atpD, glnII and recA
      (with sequence similarities of <=92 %) confirmed the unique position of BN-19(T)
      in the genus Rhizobium. DNA-DNA relatedness between the strain BN-19(T) and R.
      alkalisoli CCBAU 01393(T), R. vignae CCBAU 05176(T), R. huautlense SO2(T) and R.
      tarimense PL-41(T) were 20.6, 22.5, 15.9 and 20.5 % respectively, further
      confirming that BN-19(T) represents a novel species in the genus Rhizobium. The
      DNA G + C content was 60.1 mol%. The dominant fatty acids of strain BN-19(T) were
      C19:0 cyclo omega8c, summed feature 2 (C14:0 3OH and/or C16:1 iso I) and summed
      feature 8 (C18:1 omega7c). Some phenotypic features also differentiate the strain
      BN-19(T) from the related species. On the basis of these results, strain BN-19(T)
      is considered to represent a novel species in the genus Rhizobium, for which the
      name Rhizobium pakistanensis sp. nov. is proposed. The type strain is BN-19(T)
      (=LMG 27895(T) = CCBAU 101086(T)). 

PMID- 25391353
TI  - Streptomyces alkalithermotolerans sp. nov., a novel alkaliphilic and
      thermotolerant actinomycete isolated from a soda lake.
AB  - An alkaliphilic actinomycete, strain AC3(T), was isolated from Lonar soda lake,
      in India. Based on 16S rRNA gene sequence analysis it was identified that the
      strain belongs to the class Actinobacteria and was most closely related to
      Streptomyces sodiiphilus JCM 13581(T) (96.4 % sequence similarity), Streptomyces
      leeuwenhoekii DSM 42122(T) (96.1 %), Streptomyces albus NRRL B-2365(T) (96.1 %),
      Streptomyces panacagri Gsoil 519(T) (96.0 %), Streptomyces fimbriatus NBRC
      15411(T) (95.9 %) and other members of the genus Streptomyces (<95.9 %).The
      strain formed a well separated clade in the genus Streptomyces based on the 16S
      rRNA gene analysis of all of the validly named Streptomyces species. Strain
      AC3(T) was observed to produce light-cream substrate and white aerial mycelia on
      most tested media. The optimum pH for growth was determined to be 9.5-10.0 with
      no growth at pH 7.0. The DNA G+C content of strain AC3(T) was determined to be
      71.2 mol %. The results of the polyphasic analysis allowed a clear
      differentiation of strain AC3(T) from all other members of the genus
      Streptomyces. Strain AC3(T) is thus considered to represent a novel member of the
      genus Streptomyces, for which the name Streptomyces alkalithermotolerans sp. nov.
      is proposed. The type strain is AC3(T) (=KCTC 29497(T) = JCM 30167(T)).

PMID- 25391354
TI  - Evaluation of pre-hospital transport time of stroke patients to thrombolytic
      treatment.
AB  - BACKGROUND: Effective treatment of stroke is time dependent. Pre-hospital
      management is an important link in reducing the time from occurrence of stroke
      symptoms to effective treatment. The aim of this study was to evaluate time used
      by emergency medical services (EMS) for stroke patients during a five-year period
      in order to identify potential delays and evaluate the reorganization of EMS in
      Copenhagen in 2009. METHODS: We performed a retrospective analysis of ambulance
      records from stroke patients suitable for thrombolysis from 1 January 2006 to 7
      July 2011. We noted response time from dispatch of the ambulance to arrival at
      the scene, on-scene time and transport time to the hospital-in total, alarm-to
      door time. In addition, we noted baseline characteristics. RESULTS: We reviewed
      481 records (58% male, median age 66 years). The median (IQR) alarm-to-door time
      in minutes was 41 (33-52), of which 18 (12-24) minutes were spent on scene.
      Response time was reduced from the period before to the period after
      reorganization (7 vs. 5 minutes, p <0.001). In a linear multiple regression
      model, higher patient age and longer distance to the hospital correlated with
      significantly longer transportation time (p <0.001). CONCLUSIONS: This study
      shows an unchanged alarm-to-door time of 41 minutes over a five-year period.
      Response time, but not total alarm-to-door time, was reduced during the five
      years. On-scene time constituted nearly half of the total alarm-to-door time and
      is thus a point of focus for improvement.

PMID- 25391355
TI  - Influence of QRS duration on outcome of death or appropriate defibrillator
      therapy by strategy of left ventricular lead placement in cardiac
      resynchronization therapy recipients.
AB  - PURPOSE: Echocardiography-guided (EG) lead placement at the site of latest left
      ventricular (LV) mechanical activation improves outcome in patients receiving a
      cardiac resynchronization therapy (CRT) defibrillator (D). The purpose of this
      study is to examine whether a strategy of EG LV lead placement equally improves
      outcome in CRT recipients with wide (>=150 ms) versus intermediate (120-149 ms)
      QRS duration. METHODS: Patients treated with a CRT-D in the Speckle Tracking
      Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective,
      randomized trial (108 EG strategy and 75 routine strategy) were followed to the
      endpoint of death or first appropriate CRT-D therapy. Of the patients enrolled in
      STARTER, 115 had QRS >= 150 ms and 68 had 120 < QRS <= 149 ms. RESULTS: Over a
      mean follow-up period of 3.7 +/- 2.1 years, 62 (33 %) patients died and 40 (22 %)
      received appropriate CRT-D therapy. Compared to patients with QRS >= 150 ms,
      patients with intermediate QRS had meaningfully worse survival free from ICD
      therapy (HR = 1.48, p = 0.056). CRT-D therapy-free survival was significantly
      worse in patients with intermediate QRS duration randomized to the routine LV
      lead placement strategy, compared to patients with intermediate QRS duration
      randomized to the EG LV lead placement strategy or patients with wide QRS
      duration regardless of LV implantation strategy (HR = 2.08, 95 % confidence
      interval = 1.21-3.56, P = 0.008). This finding was independent in type of
      cardiomyopathy. CONCLUSION: A strategy of EG LV lead placement improves survival
      free from defibrillator therapy in patients with QRS between 120-149 ms to levels
      comparable to those of patients with QRS >= 150 ms.

PMID- 25391356
TI  - High throughput secondary electron imaging of organic residues on a graphene
      surface.
AB  - Surface organic residues inhibit the extraordinary electronic properties of
      graphene, hindering the development of graphene electronics. However, fundamental
      understanding of the residue morphology is still absent due to a lack of high
      throughput and high-resolution surface characterization methods. Here, we
      demonstrate that secondary electron (SE) imaging in the scanning electron
      microscope (SEM) and helium ion microscope (HIM) can provide sub-nanometer
      information of a graphene surface and reveal the morphology of surface
      contaminants. Nanoscale polymethyl methacrylate (PMMA) residues are visible in
      the SE imaging, but their contrast, i.e. the apparent lateral dimension, varies
      with the imaging conditions. We have demonstrated a quantitative approach to
      readily obtain the physical size of the surface features regardless of the
      contrast variation. The fidelity of SE imaging is ultimately determined by the
      probe size of the primary beam. HIM is thus evaluated to be a superior SE imaging
      technique in terms of surface sensitivity and image fidelity. A highly efficient
      method to reveal the residues on a graphene surface has therefore been
      established. 

PMID- 25391357
TI  - Adapting supported employment for emerging adults with serious mental health
      conditions.
AB  - Effective services are needed to assist young people with serious mental health
      conditions to successfully transition to employment or education, especially
      among those with intensive adolescent mental health service utilization. To meet
      these needs, the Individual Placement and Support (IPS) model of supported
      employment was adapted and its feasibility was tested in a psychiatric treatment
      program for early-emerging adults. Participants were 17-20 years old (mean age =
      18.5 years). Most were African American, under the custody of the state, with a
      primary mood disorder diagnosis. Adaptations to IPS included adding the
      following: near age peer mentors, a supported education component, and a career
      development focus. This open trial feasibility study tracked the model's
      development, recruitment, and retention and tracked vocational and educational
      outcomes for 12 months. Model refinement resulted in the development of a
      separate educational specialist position, greater integration of the peer mentor
      with the vocational team, and further specification of the role of peer mentor.
      There was an 80% retention rate in the feasibility evaluation. Of the 35
      participants, 49% started a job and/or enrolled in an education program over the
      12-month period. 

PMID- 25391358
TI  - An Exploratory Study of Conflict and Its Management in Systems of Care for
      Children with Mental, Emotional, or Behavioral Problems and Their Families.
AB  - Since 1993, the Substance Abuse and Mental Health Services Administration has
      invested more than $1 billion establishing systems of care (SOC) in over 173
      local communities to provide services to children with mental, emotional, and
      behavioral problems and their families. The SOC model requires that effective
      partnerships be developed between parents and professionals and also among
      different service sectors and agencies. To date, there has been no systematic
      examination of these interagency partnerships associated with the presence of
      conflict and its management. This paper reports the findings from a survey of the
      members of the governing boards of currently funded and graduated SOC sites
      related to interorganizational conflict. The results indicated that conflict was
      common in SOC regardless of the stage of the system's development. The most
      common types of conflict included incompatible goals, interpersonal
      relationships, and overlapping authority. When conflict occurred, a number of
      management efforts were used including analyzing the conflict and developing a
      strategy to deal with it and dealing with the conflict behind the scenes.
      Suggestions are provided for identifying and managing conflict. 

PMID- 25391359
TI  - From Curves to Trees: A Tree-like Shapes Distance Using the Elastic Shape
      Analysis Framework.
AB  - Trees are a special type of graph that can be found in various disciplines. In
      the field of biomedical imaging, trees have been widely studied as they can be
      used to describe structures such as neurons, blood vessels and lung airways. It
      has been shown that the morphological characteristics of these structures can
      provide information on their function aiding the characterization of pathological
      states. Therefore, it is important to develop methods that analyze their shape
      and quantify differences between their structures. In this paper, we present a
      method for the comparison of tree-like shapes that takes into account both
      topological and geometrical information. This method, which is based on the
      Elastic Shape Analysis Framework, also computes the mean shape of a population of
      trees. As a first application, we have considered the comparison of axon
      morphology. The performance of our method has been evaluated on two sets of
      images. For the first set of images, we considered four different populations of
      neurons from different animals and brain sections from the NeuroMorpho.org open
      database. The second set was composed of a database of 3D confocal microscopy
      images of three populations of axonal trees (normal and two types of mutations)
      of the same type of neurons. We have calculated the inter and intra class
      distances between the populations and embedded the distance in a classification
      scheme. We have compared the performance of our method against three other state
      of the art algorithms, and results showed that the proposed method better
      distinguishes between the populations. Furthermore, we present the mean shape of
      each population. These shapes present a more complete picture of the
      morphological characteristics of each population, compared to the average value
      of certain predefined features. 

PMID- 25391361
TI  - Case of paraneoplastic retinopathy with retinal ON-bipolar cell dysfunction and
      subsequent resolution of ERGs.
AB  - PURPOSE: To report a patient with cancer-associated retinopathy and retinal ON
      bipolar cell dysfunction who had a resolution of the electroretinograms (ERGs)
      after a resection of an ovarian cancer and chemotherapy. CASE REPORT: A 71-year
      old Japanese female patient visited us complaining of night blindness and
      photopsia in both eyes for 6 months. Her visual acuity was 20/20 in both eyes,
      and fundus examination, fluorescence angiography, and optical coherence
      tomography showed no abnormalities in both eyes. The rod responses of the ERGs
      were absent and bright-flash ERGs were electronegative. The ON responses of the
      focal macular ERGs and full-field long-flash ERGs were absent. These ERG findings
      indicate an ON-bipolar cell dysfunction. A general physical examination revealed
      the presence of ovarian cancer. After resection of the ovarian cancer and
      adjuvant chemotherapy, the ERGs of the left eye completely recovered within 2
      years and those of right eye recovered subsequently. The autoantibody against
      transient receptor potential melastatin 1 (TRPM1) was not detected in the serum.
      CONCLUSION: Our case demonstrates that retinal ON-bipolar dysfunction can be
      caused by ovarian cancer. Our case indicates that some autoantibodies against
      other than TRPM1 might cause transient dysfunction of retinal ON-bipolar cells.

PMID- 25391362
TI  - Colorectal cancer: elongation is essential.

PMID- 25391364
TI  - [Case of sleep apnea syndrome with dizziness markedly recovered with CPAP].

PMID- 25391363
TI  - Molecular adaptations in vasoactive systems during acute stroke in salt-induced
      hypertension.
AB  - Investigations regarding hypertension and dietary sodium, both factors that
      influence stroke risk, have previously been limited to using genetically
      disparate treatment and control groups, namely the stroke-prone, spontaneously
      hypertensive rat and Wistar-Kyoto rat. In this investigation, we have
      characterized and compared cerebral vasoactive system adaptations following
      stroke in genetically identical, salt-induced hypertensive, and normotensive
      control mice. Briefly, ANP(+/-) (C57BJ/6 * SV129 background) mice were fed chow
      containing either 0.8% NaCl (NS) or 8.0% NaCl (HS) for 7 weeks. Transient
      cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Infarct
      volumes were measured 24-h post-reperfusion and the mRNA expression of five major
      vasoactive systems was characterized using qPCR. Along with previous
      publications, our data validate a salt-induced hypertensive state in ANP(+/-)
      mice fed HS chow as they displayed left ventricular hypertrophy, increased
      systolic blood pressure, and increased urinary sodium excretion. Following MCAO,
      mice fed HS exhibited larger infarct volumes than their dietary counterparts. In
      addition, significant up-regulation in Et-1 and Nos3 mRNA expression in response
      to salt and stroke suggests implications with increased cerebral damage in this
      group. In conclusion, our data demonstrate increased cerebral susceptibility to
      stroke in salt-induced hypertensive mice. More importantly, however, we have
      characterized a novel method of investigating hypertension and stroke with the
      use of genetically identical treatment and control groups. This is the first
      investigation in which genetic confounding variables have been eliminated.

PMID- 25391365
TI  - Coagulation profile changes and safety of epidural analgesia after hepatectomy: a
      retrospective study.
AB  - PURPOSE: We aimed to review post-hepatectomy coagulation profile changes, to
      assess outcomes of epidural catheter placement in post-hepatectomy patients, and
      to make justifications regarding use of epidural analgesia in patients undergoing
      hepatectomy. METHODS: We performed a retrospective study of 141 patients
      undergoing liver resection at Brigham and Women's Hospital between January 1,
      2007 and December 31, 2011. All patients were between 21 and 85 years old, with
      ASA physical status classification of II or III, and Child-Pugh scores <=6.
      Patients undergoing laparoscopy or resection of less than three hepatic segments
      were excluded. We examined pre-operative hematocrit, platelet count, coagulation
      studies, and liver function tests, and trended values for 7 post-operative days.
      We examined frequency of epidural placement, use of peri-operative
      anticoagulation, and incidence of epidural-related complications. RESULTS: We
      demonstrated statistically significant decreases in hematocrit and platelet
      counts, as well as statistically significant increases in prothrombin time and
      international normalized ratio (INR) values. Thirty-two percent of patients
      required vitamin K or fresh frozen plasma to achieve an INR <=1.3. No patient
      required platelet transfusion to achieve platelets >=100,000 prior to catheter
      removal. Changes in post-operative partial thromboplastin time were not
      significant. Epidural catheters were placed in 90% of liver resections performed
      at our institution. We noted no epidural hematomas, even in the 7% of patients in
      whom the epidural catheter was inadvertently removed before coagulation criteria
      were met. The latter group was monitored with hourly neurologic exams for 24 h.
      CONCLUSION: Epidural analgesia may be safely used in patients undergoing major
      hepatic resection, providing that they have normal pre-operative coagulation and
      catheters are removed only when resection-induced perioperative coagulopathy has
      resolved or has been corrected.

PMID- 25391367
TI  - Crown ethers in graphene.
AB  - Crown ethers are at their most basic level rings constructed of oxygen atoms
      linked by two- or three-carbon chains. They have attracted attention for their
      ability to selectively incorporate various atoms or molecules within the cavity
      formed by the ring. However, crown ethers are typically highly flexible,
      frustrating efforts to rigidify them for many uses that demand higher binding
      affinity and selectivity. Here we present atomic-resolution images of the same
      basic structures of the original crown ethers embedded in graphene. This
      arrangement constrains the crown ethers to be rigid and planar. First-principles
      calculations show that the close similarity of the structures should also extend
      to their selectivity towards specific metal cations. Crown ethers in graphene
      offer a simple environment that can be systematically tested and modelled. Thus,
      we expect that our finding will introduce a new wave of investigations and
      applications of chemically functionalized graphene. 

PMID- 25391366
TI  - The Aspergillus nidulans metZ gene encodes a transcription factor involved in
      regulation of sulfur metabolism in this fungus and other Eurotiales.
AB  - In Aspergillus nidulans, expression of sulfur metabolism genes is activated by
      the MetR transcription factor containing a basic region and leucine zipper domain
      (bZIP). Here we identified and characterized MetZ, a new transcriptional
      regulator in A. nidulans and other Eurotiales. It contains a bZIP domain similar
      to the corresponding region in MetR and this similarity suggests that MetZ could
      potentially complement the MetR deficiency. The metR and metZ genes are
      interrupted by unusually long introns. Transcription of metZ, unlike that of
      metR, is controlled by the sulfur metabolite repression system (SMR) dependent on
      the MetR protein. Overexpression of metZ from a MetR-independent promoter in a
      DeltametR background activates transcription of genes encoding sulfate permease,
      homocysteine synthase and methionine permease, partially complementing the
      phenotype of the DeltametR mutation. Thus, MetZ appears to be a second
      transcription factor involved in regulation of sulfur metabolism genes. 

PMID- 25391368
TI  - Unusual neurological manifestation of severe digitoxin intoxication with
      bilateral ballism and visual hallucinations.

PMID- 25391369
TI  - A reduction in reactive oxygen species contributes to dihydromyricetin-induced
      apoptosis in human hepatocellular carcinoma cells.
AB  - Reactive oxygen species (ROS) and cellular oxidant stress are considered inducers
      of carcinogenesis. However, the association of ROS with cancer is both complex
      and, at times, paradoxical. We assessed the effects of dihydromyricetin (DHM) on
      the induction of ROS accumulation and on the activation of the mitochondrial
      signaling pathway in human hepatoma HepG2 cells. The results indicated that DHM
      could reduce ROS accumulation in a concentration-dependent manner. Additionally,
      with increasing concentrations of DHM, the expression of proteins that
      participate in the cell apoptosis program increased in a concentration-dependent
      manner. Furthermore, we found that a low dose of H2O2 (10 nM) could reverse DHM
      induced cell apoptosis. We observed the following critical issues: first, the
      cellular redox balance is vital in DHM-induced apoptosis of human hepatocellular
      carcinoma (HCC) cells, and second, ROS could function as a redox-active signaling
      messenger to determine DHM-induced cell apoptosis. In this study, we demonstrated
      that low levels of ROS are also critical for the function of HCC cells.

PMID- 25391370
TI  - [Polyarteritis nodosa: differential diagnostics and therapy].
AB  - Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium size arteries
      that may affect various organs. The clinical appearance is very variable. The
      most common manifestations are of the skin, the peripheral nervous system
      presenting as mononeuritis multiplex and the mesenteric and renal blood vessels
      due to the development of stenoses and small aneurysms. Of the cases one third
      are estimated to be associated with hepatitis B virus (HBV). The therapy depends
      on the pathogenesis of the disease: primary PAN is treated with
      immunosuppressants, whereas patients with HBV-related PAN should receive
      antiviral therapy and plasmapheresis. Differentiating PAN from other forms of
      vasculitis can be difficult and requires complex differential diagnostics. 

PMID- 25391371
TI  - Targeting FoxM1 by thiostrepton inhibits growth and induces apoptosis of
      laryngeal squamous cell carcinoma.
AB  - PURPOSE: We have previously reported that forkhead box M1 (FoxM1) transcription
      factor was overexpressed in laryngeal squamous cell carcinoma (LSCC) and was
      associated with development of LSCC. However, there are limited studies regarding
      the functional significance of FoxM1 and FoxM1 inhibitor thiostrepton in LSCC.
      Therefore, the aim of this study was to examine both in vitro and in vivo
      activity of FoxM1 inhibitor thiostrepton against LSCC cell line and nude mice.
      METHODS: Cell viability was studied by CCK-8 assay. Cell growth was evaluated by
      CFSE staining and cell cycle analysis. Apoptosis was measured by flow cytometry.
      The mRNA and protein expression were detected by quantitative real-time RT-PCR,
      Western blot and immunohistochemical staining. Xenograft model of tumor formation
      was used to investigate how thiostrepton influences tumorigenesis in vivo.
      RESULTS: Overexpression of FoxM1 in LSCC cells was down-regulated by thiostrepton
      in a dose-dependent manner. Thiostrepton caused dose- and time-dependent
      suppression of cell viability of LSCC. Moreover, thiostrepton induced cell cycle
      arrest at S phase at early time and inhibited DNA synthesis in LSCC cells in a
      dose- and time-dependent manner by down-regulation of cyclin D1 and cyclin E1.
      Thiostrepton also induced dose- and time-dependent apoptosis of LSCC cells by
      down-regulation of Bcl-2, up-regulation of Bax and p53, and inducing release of
      cytochrome c accompanied by activation of cleaved caspase-9, cleaved caspase-3
      and cleaved PARP. In addition, z-VAD-fmk, a universal inhibitor of caspases,
      prevented activation of cleavage caspase-3 and abrogates cell death induced by
      thiostrepton treatment. Furthermore, FADD and cleaved caspase-8 were activated,
      and expression of cIAP1, XIAP and survivin were inhibited by thiostrepton.
      Finally, treatment of LSCC cell line xenografts with thiostrepton resulted in
      tumorigenesis inhibition of tumors in nude mice by reducing proliferation and
      inducing apoptosis of LSCC cells. CONCLUSIONS: Collectively, our finding suggest
      that targeting FoxM1 by thiostrepton inhibit growth and induce apoptosis of LSCC
      through mitochondrial- and caspase-dependent intrinsic pathway and Fas-dependent
      extrinsic pathway as well as IAP family. Thiostrepton may represent a novel lead
      compound for targeted therapy of LSCC.

PMID- 25391372
TI  - Effects of red laser, infrared, photodynamic therapy, and green LED on the
      healing process of third-degree burns: clinical and histological study in rats.
AB  - The aim of this study was to evaluate the effects of red laser, infrared,
      photodynamic therapy, and green light-emitting diode (LED) on the healing process
      of skin burns through clinical and histopathologic analysis in rats. For this,
      100 animals were randomly divided into five groups: G1-untreated control (CTR),
      G2-red laser (LVER), G3-infrared (LINF), G4-photodynamic therapy (PDT), and G5
      green LED. Burn was induced on the dorsum of the rat and the treatment of the
      experimental groups was red light (10 J/cm(2), 10 s, 40 mW, and lambda660 nm),
      infrared (10 J/cm(2), 10 s, 40 mW, and lambda780 nm), green LED irradiation (60
      J/cm(2), 10 s, lambda520, and 550 nm), and photodynamic therapy (10 J/cm(2), 40
      mW, and lambda660 nm), the latter combined with methylene blue photosensitizer at
      concentration 0.5 MUg/mL. Applications were performed daily until day prior to
      sacrifice of the animal at 3, 7, 14, and 21 days with intraperitoneal anesthetic
      overdose. The specimens collected were clinically examined and soon after
      processed and stained with hematoxylin-eosin and Picrosirius for analysis under
      light and polarized light microscopy, respectively. Animals treated with LVER,
      LINF, PDT (p < 0.001), and LED (p < 0.05) stimulated production and maturation of
      collagen, and increased the consumption of food and water compared to the CTR (p
      < 0.001). Laser lambda660 nm and lambda780 nm showed the largest wound reductions
      in all groups (p = 0.001). In conclusion, red laser, infrared, photodynamic
      therapy, and green LED favored the healing process of third-degree burns in rats.

PMID- 25391373
TI  - Watchdog orders tobacco company to remove advertisement for smoking app.

PMID- 25391374
TI  - Insulin-like growth factor-1 receptor signaling increases the invasive potential
      of human epidermal growth factor receptor 2-overexpressing breast cancer cells
      via Src-focal adhesion kinase and forkhead box protein M1.
AB  - Resistance to the human epidermal growth factor receptor (HER2)-targeted antibody
      trastuzumab is a major clinical concern in the treatment of HER2-positive
      metastatic breast cancer. Increased expression or signaling from the insulin-like
      growth factor-1 receptor (IGF-1R) has been reported to be associated with
      trastuzumab resistance. However, the specific molecular and biologic mechanisms
      through which IGF-1R promotes resistance or disease progression remain poorly
      defined. In this study, we found that the major biologic effect promoted by IGF
      1R was invasion, which was mediated by both Src-focal adhesion kinase (FAK)
      signaling and Forkhead box protein M1 (FoxM1). Cotargeting IGF-1R and HER2 using
      either IGF-1R antibodies or IGF-1R short hairpin RNA in combination with
      trastuzumab resulted in significant but modest growth inhibition. Reduced
      invasion was the most significant biologic effect achieved by cotargeting IGF-1R
      and HER2 in trastuzumab-resistant cells. Constitutively active Src blocked the
      anti-invasive effect of IGF-1R/HER2 cotargeted therapy. Furthermore, knockdown of
      FoxM1 blocked IGF-1-mediated invasion, and dual targeting of IGF-1R and HER2
      reduced expression of FoxM1. Re-expression of FoxM1 restored the invasive
      potential of IGF-1R knockdown cells treated with trastuzumab. Overall, our
      results strongly indicate that therapeutic combinations that cotarget IGF-1R and
      HER2 may reduce the invasive potential of cancer cells that are resistant to
      trastuzumab through mechanisms that depend in part on Src and FoxM1. 

PMID- 25391376
TI  - Experimental transmission of AA amyloidosis by injecting the AA amyloid protein
      into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.
AB  - The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and
      several animal species, including cats and cattle with prolonged inflammation. AA
      amyloidosis can be experimentally induced in mice using severe inflammatory
      stimuli and a coinjection of AA amyloid; however, difficulties have been
      associated with transmitting AA amyloidosis to a different animal species, and
      this has been attributed to the "species barrier." The interleukin-1 receptor
      antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid
      arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and
      BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a
      subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were
      injected with crude or purified murine AA amyloid developed AA amyloidosis.
      However, the amyloid index, which was determined by the intensity of AA amyloid
      deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When
      IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid
      together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO
      mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively,
      developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected
      with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of
      IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice,
      respectively, developed AA amyloidosis. These results indicated that IL-1raKO
      mice are a useful animal model for investigating AA amyloidogenesis.

PMID- 25391375
TI  - TP53 engagement with the genome occurs in distinct local chromatin environments
      via pioneer factor activity.
AB  - Despite overwhelming evidence that transcriptional activation by TP53 is critical
      for its tumor suppressive activity, the mechanisms by which TP53 engages the
      genome in the context of chromatin to activate transcription are not well
      understood. Using a compendium of novel and existing genome-wide data sets, we
      examined the relationship between TP53 binding and the dynamics of the local
      chromatin environment. Our analysis revealed three distinct categories of TP53
      binding events that differ based on the dynamics of the local chromatin
      environment. The first class of TP53 binding events occurs near transcriptional
      start sites (TSS) and is defined by previously characterized promoter-associated
      chromatin modifications. The second class comprises a large cohort of
      preestablished, promoter-distal enhancer elements that demonstrates dynamic
      histone acetylation and transcription upon TP53 binding. The third class of TP53
      binding sites is devoid of classic chromatin modifications and, remarkably, fall
      within regions of inaccessible chromatin, suggesting that TP53 has intrinsic
      pioneer factor activity and binds within structurally inaccessible regions of
      chromatin. Intriguingly, these inaccessible TP53 binding sites feature several
      enhancer-like properties in cell types within the epithelial lineage, indicating
      that TP53 binding events include a group of "proto-enhancers" that become active
      enhancers given the appropriate cellular context. These data indicate that TP53,
      along with TP63, may act as pioneer factors to specify epithelial enhancers.
      Further, these findings suggest that rather than following a global cell-type
      invariant stress response program, TP53 may tune its response based on the
      lineage-specific epigenomic landscape. 

PMID- 25391377
TI  - Notifiable disease reporting among public sector physicians in Nigeria: a cross
      sectional survey to evaluate possible barriers and identify best sources of
      information.
AB  - BACKGROUND: Since 2001, Nigeria has collected information on epidemic-prone and
      other diseases of public health importance through the Integrated Disease
      Surveillance and Response system (IDSR). Currently 23 diseases are designated as
      "notifiable" through IDSR, including human infection with avian influenza (AI).
      Following an outbreak of highly pathogenic avian influenza A(H5N1) in Nigerian
      poultry populations in 2006 and one laboratory confirmed human infection in 2007,
      a study was carried out to describe knowledge, perceptions, and practices related
      to infectious disease reporting through the IDSR system, physicians' preferred
      sources of heath information, and knowledge of AI infection in humans among
      public sector physicians in Nigeria. METHODS: During November to December 2008,
      245 physicians in six Nigerian cities were surveyed through in-person interviews.
      Survey components included reporting practices for avian influenza and other
      notifiable diseases, perceived obstacles to disease reporting, methods for
      obtaining health-related information, and knowledge of avian influenza among
      participating physicians. RESULTS: All 245 respondents reported that they had
      heard of AI and that humans could become infected with AI. Two-thirds (163/245)
      had reported a notifiable disease. The most common perceived obstacles to
      reporting were lack of infrastructure/logistics or reporting system (76/245,
      31%), lack of knowledge among doctors about how to report or to whom to report
      (64/245, 26%), and that doctors should report certain infectious diseases
      (60/245, 24%). Almost all participating physicians (>99%) reported having a cell
      phone that they currently use, and 86% reported using the internet at least
      weekly. CONCLUSIONS: Although the majority of physicians surveyed were
      knowledgeable of and had reported notifiable diseases, they identified many
      perceived obstacles to reporting. In order to effectively identify human AI cases
      and other infectious diseases through IDSR, reporting system requirements need to
      be clearly communicated to participating physicians, and perceived obstacles,
      such as lack of infrastructure, need to be addressed. Future improvements to the
      reporting system should account for increased utilization of the internet, as
      well as cell phone and email-based communication.

PMID- 25391378
TI  - Is there a role for human pluripotent stem cells in modelling interstitial cells
      of Cajal and gut motility disorders?
AB  - Gastrointestinal motility disorders affect millions of people worldwide,
      resulting in significant morbidity and mortality. Current treatments for these
      disorders are inadequate and often provide little to no relief for patients. As a
      result, gastrointestinal motility disorders produce substantial long-term social
      and economic burdens in both developed and developing countries. These limited
      treatment options arise largely from our relatively poor understanding of the
      molecular etiology for the majority of gastrointestinal motility disorders. In
      turn, this is due to our limited access to normal or diseased human gut tissue
      for use in research. In particular while the interstitial cells of Cajal (ICC)
      are known to be important for gastrointestinal motility, little is known of how
      these cells function or how they are involved in disease initiation and
      progression. The advent of human pluripotent stem cell technology offers an
      opportunity to generate large amounts of human tissue for both research and
      clinical applications. The application of this technology to gastrointestinal
      motility disorders is currently only in its infancy and as yet no studies have
      described ICC production from human pluripotent cells. By considering the present
      understanding of the anatomical, cellular and molecular basis of gut motility
      with particular emphasis on ICC, this review provides a clear framework for the
      application of human pluripotent stem cell technology to answer fundamental
      questions of ICC involvement in gut motility. 

PMID- 25391379
TI  - Alternative splicing regulates pluripotent state in pluripotent stem cells.
AB  - Alternative splicing (AS) generates multiple mature mRNAs from a single pre-mRNA,
      so AS is the main contributor for the diversity of the proteins, participating in
      most of the cellular processes. For pluripotent stem cells (PSCs), great effort
      has been made to search for pluripotency-related genes and their regulatory
      mechanisms. However, the sophisticated regulation still remains to be clear.
      Recent studies indicate that stem cells undergo a unique AS pattern and have a
      different protein expression profile from differentiated cells, giving a new clue
      that AS switching or AS itself may play a significant role in the processes of
      differentiation and somatic reprogramming. Indeed, accumulating evidences prove
      that AS plays critical roles in maintaining pluripotent homeostasis in PSCs. In
      this review, we summarized recent researches on AS in ESCs and iPSCs, including
      some distinct AS events in pluripotent cells, and then discussed the new progress
      on mechanisms for AS in ESCs and iPSCs differentiation and somatic reprogramming.

PMID- 25391380
TI  - Clinical outcomes of the transplantation of stem cells from various human tissue
      sources in the management of liver cirrhosis: a systematic review and meta
      analysis.
AB  - AIMS: A systematic review and meta-analysis were performed to explore the
      clinical outcome of the transplantation of stem cells from various human tissue
      sources in cirrhotic patients. METHODS: The relevant papers were searched via
      PubMed, EMBASE, and Cochrane Library databases. Changes in liver function before
      and after stem cell therapy were evaluated (self-control data). Difference in
      liver function and incidence of procedure-related complications, hepatocellular
      carcinoma (HCC), and death between patients undergoing stem cell therapy and
      conventional treatment were evaluated (case-control data). RESULTS: Of 786 papers
      initially identified, 31 were included. The sources of stem cell included bone
      marrow (n=26), umbilical cord (n=3), peripheral blood (n=1), and human fetal
      liver (n=1). No severe procedure-related complications were reported. According
      to the meta- analyses of self-control data, model for end-stage liver diseases
      (MELD) score was significantly reduced at the 3rd-4th and 6th months after stem
      cell therapy, but this reduction was not statistically significant at the 1st-2nd
      or 12th postoperative months. Child-Pugh score was also reduced after stem cell
      therapy, but the reduction was not statistically significant at all follow-up
      time points. According to the meta-analyses of case-control data, MELD and Child
      Pugh scores were not significantly different between treatment and control groups
      at all follow-up time points. The incidence of HCC was not significantly
      different between treatment and control groups (odds ratio [OR] to=0.41, P=0.53).
      The mortality was not significantly different between the two groups (OR=0.48,
      P=0.20). CONCLUSION: Stem cell therapy could improve the liver function without
      any severe procedure-related complications. However, compared with conventional
      treatment, the benefit of stem cell therapy appeared to be not significant in
      improving the liver function and survival.

PMID- 25391382
TI  - Antidementia drug treatment in people screened positive for dementia in primary
      care.
AB  - BACKGROUND: There is a lack of knowledge about antidementia drug treatment in
      community dwelling people with dementia in Germany. OBJECTIVE: To determine the
      frequency of treatment with antidementia drugs in patients in primary care, and
      the socio-demographic and clinical variables associated with antidementia drug
      treatment. METHODS: Present analyses are based on preliminary data from the
      DelpHi-trial, an ongoing GP-based, cluster-randomized, controlled intervention
      trial to implement and evaluate an innovative concept of collaborative dementia
      care management in Germany. Our sample consists of n = 243 subjects who screened
      positive for dementia. RESULTS: 29.6% (n = 72) of participants received
      antidementia drugs: memantine 44.5% (n = 32); donepezil 30.5% (n = 22);
      rivastigmine 13.9% (n = 10); galantamine 11.1% (n = 8). A total of 46.4% (n = 45)
      of the subgroup of participants with a formal dementia diagnosis received
      antidementia drug treatment. Approximately 37.5% (n = 27) of our sample received
      treatment with antidementia drugs without having a formal diagnosis. Treatment
      with antidementia drugs was significantly associated with more severe cognitive
      impairment and having a formal dementia diagnosis. CONCLUSIONS: One in three
      people who screened positive for dementia in primary care received antidementia
      drug treatment, indicating the frequent use of this class of drugs. For those
      with a formal dementia diagnosis, these drug treatment rates are more than
      triple, compared to those in nursing homes.

PMID- 25391381
TI  - Bach1 overexpression in Down syndrome correlates with the alteration of the HO
      1/BVR-a system: insights for transition to Alzheimer's disease.
AB  - Bach1, among the genes encoded on chromosome 21, is a transcription repressor,
      which binds to antioxidant response elements of DNA thus inhibiting the
      transcription of specific genes involved in the cell stress response including
      heme oxygenase-1 (HO-1). HO-1 and its partner, biliverdin reductase-A (BVR-A),
      are upregulated in response to oxidative stress in order to protect cells against
      further damage. Since oxidative stress is an early event in Down syndrome (DS)
      and might contribute to the development of multiple deleterious DS phenotypes,
      including Alzheimer's disease (AD) pathology, we investigated the status of the
      Bach1/HO-1/BVR-A axis in DS and its possible implications for the development of
      AD. In the present study, we showed increased total Bach1 protein levels in the
      brain of all DS cases coupled with reduced induction of brain HO-1. Furthermore,
      increased oxidative stress could, on one hand, overcome the inhibitory effects of
      Bach1 and, on the other hand, promote BVR-A impairment. Our data show that the
      development of AD in DS subjects is characterized by (i) increased Bach1 total
      and poly-ubiquitination; (ii) increased HO-1 protein levels; and (iii) increased
      nitration of BVR-A followed by reduced activity. To corroborate our findings, we
      analyzed Bach1, HO-1, and BVR-A status in the Ts65Dn mouse model at 3 (young) and
      15 (old) months of age. The above data support the hypothesis that the
      dysregulation of HO-1/BVR-A system contributes to the early increase of oxidative
      stress in DS and provide potential mechanistic paths involved in the
      neurodegenerative process and AD development. 

PMID- 25391383
TI  - Genetic variation in imprinted genes is associated with risk of late-onset
      Alzheimer's disease.
AB  - Epigenetic changes including genomic imprinting may affect risk of late-onset
      Alzheimer's disease (LOAD). There are >100 known imprinted genes and most of them
      are expressed in human brain. In this study, we examined the association of
      single nucleotide polymorphisms (SNPs) in 93 imprinted genes with LOAD risk in
      1291 LOAD cases and 958 cognitively normal controls. We performed single-site,
      gene-based, and haplotype analyses. Single-site analysis showed 14 significant
      associations at p < 0.01. The most significant SNP (rs11770199; p = 0.0003) in
      single-site analysis was located on chromosome 7 in the GRB10 gene. Gene-based
      analyses revealed four significant associations in the WT1, ZC3H12C, DLGAP2, and
      GPR1 genes at p < 0.05. The haplotype analysis also revealed significant
      associations with three genes (ZC3H12C, DLGAP2, and GPR1). These findings suggest
      a possible role of imprinted genes in AD pathogenesis that show specific
      expression in the brain. 

PMID- 25391384
TI  - Apolipoprotein e4 affects topographical changes in hippocampal and cortical
      atrophy in Alzheimer's disease dementia: a five-year longitudinal study.
AB  - Apolipoprotein E4 (APOE4) is a genetic risk factor for developing Alzheimer's
      disease (AD). Once AD manifests clinically, however, the effects of APOE4 are
      less clear. Therefore, we investigated the longitudinal effects of APOE4 on
      topographical changes in AD patient brain atrophy. We prospectively recruited 35
      patients with AD (19 APOE4 carriers and 16 non-carriers), and 14 normal controls,
      then followed them for five years. We measured hippocampal deformities and
      cortical thickness. Hippocampal comparison between APOE4 carriers and non
      carriers with AD showed carriers had rapid changes in the head and body, while
      non-carriers had rapid changes in a small portion of the body. Cortical thickness
      comparison between APOE4 carriers and non-carriers with AD dementia showed
      carriers had rapid thinning in the lateral frontal, temporal, and parietal
      regions, while no region showed more rapid cortical thinning in non-carriers than
      in carriers. These findings underlined the importance of the APOE4 allele for
      designing and interpreting future treatment trials in patients with AD dementia. 

PMID- 25391385
TI  - Cerebrospinal fluid biomarkers distinguish postmortem-confirmed Alzheimer's
      disease from other dementias and healthy controls in the OPTIMA cohort.
AB  - Cerebrospinal fluid (CSF) amyloid-beta (Abeta) and tau have been studied as
      markers of Alzheimer's disease (AD). Combined Abeta42 and t-tau distinguishes AD
      from healthy controls with a sensitivity and specificity (sens/spec) near 89%
      across studies. This study examined these markers in the homogeneous OPTIMA
      cohort, using extensive longitudinal follow up and postmortem evaluation to
      confirm clinicopathological status. Baseline CSF was analyzed from 227
      participants with AD (97% autopsy-confirmed), mild cognitive impairment (MCI; 73%
      confirmed), other dementia syndrome (ODS; 100% confirmed), and controls (CTL; 27%
      confirmed, follow up approximately 9-13 years). Biomarker concentrations were
      analyzed using validated ELISAs. AD patients had lower CSF Abeta42 and higher t
      tau, p-tau, t-tau/Abeta42, and t-tau/Abeta40 compared to CTLs, with MCI
      intermediate. CTL and MCI participants who progressed to AD demonstrated more AD
      like profiles. Abeta40, sAbetaPPalpha, and sAbetaPPbeta were lower in AD compared
      to CTL. High-level discriminators of AD from CTL were t-tau/Abeta40 (AUROC 0.986,
      sens/spec of 92%/94%), p-tau/Abeta42 (AUROC 0.972, sens/spec of 94%/90%), and
      Abeta42 (AUROC 0.941, sens/spec of 88%). For discriminating AD from ODS, p
      tau/Abeta42 demonstrated sens/spec of 88%/100% (95%/86% at the AD versus CTL
      cutoff) and Abeta42 demonstrated sens/spec of 84%/100% (88%/100% at the AD versus
      CTL cutoff). In a well-characterized, homogeneous population, a single cutoff for
      baseline CSF Abeta and tau markers can distinguish AD with a high level of
      sens/spec compared to other studies. It may be important to characterize sources
      of demographic and biological variability to support the effective use of CSF
      diagnostic assays in the broader AD population. 

PMID- 25391386
TI  - Aspiration and sclerotherapy versus hydrocoelectomy for treating hydrocoeles.
AB  - BACKGROUND: Hydrocoeles are common cystic scrotal abnormalities, described as a
      fluid-filled collection between the visceral and parietal layers of the tunica
      vaginalis of the scrotum. There are two approaches for treatment of hydrocoeles:
      surgical open hydrocoelectomy and aspiration followed by sclerotherapy. 
      OBJECTIVES: We compared the benefits and harms of aspiration and sclerotherapy
      versus hydrocoelectomy for the management of hydrocoeles. SEARCH METHODS: We
      searched the Cochrane Renal Group's Specialised Register to 2 August 2014 through
      contact with the Trials' Search Co-ordinator using search terms relevant to this
      review. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs
      comparing aspiration and sclerotherapy versus hydrocoelectomy for the management
      of hydrocoeles. DATA COLLECTION AND ANALYSIS: Two authors independently extracted
      data and assessed risk of bias in the included studies. Random effects meta
      analyses were performed using relative risk (RR) for dichotomous outcomes and
      mean differences (MD) for continuous outcomes, with 95% confidence intervals
      (CI). MAIN RESULTS: We found four small studies that met the inclusion criteria.
      These studies enrolled 275 patients with 282 hydroceles. Participants were
      randomised to aspiration and sclerotherapy (155 patients with 159 hydroceles) and
      surgery (120 patients with 123 hydroceles). All studies were assessed as having
      low or unclear risk of bias for selection bias, detection bias, attrition bias
      and selective reporting bias. Blinding was not possible for participants and
      investigators based on the type of interventions. Blinding for statisticians was
      not reported in any of included studies.There were no significant difference in
      clinical cure between the two groups (3 studies, 215 participants: RR 0.45, 95%
      CI 0.18 to 1.10), however there was significant heterogeneity (I2 = 95%). On
      further investigation one study contributed all of the heterogeneity. This could
      be due to the agent used or perhaps due to the fact that this is a much older
      study than the other two studies included in this analysis. When this study was
      removed from the analysis the heterogeneity was 0% and the result was significant
      (in favour of surgery) (2 studies, 136 participants: RR 0.74; 95% CI 0.64 to
      0.85).There was a significant increase in recurrence in those who received
      sclerotherapy compared with surgery (3 studies, 196 participants: RR 9.37, 95% CI
      1.83 to 48.4). One study reported a non-significant decrease in fever in the
      sclerotherapy group (60 participants: RR 0.25, 95% CI 0.06 to 1.08). There was an
      increased number of infections in the surgery group however this increase was not
      statistically significant (4 studies, 275 participants): RR 0.31, 95% CI 0.09 to
      1.05; I2 = 0%). Three studies reported the frequency of pain in the surgery group
      was higher than aspiration and sclerotherapy group but because of different
      measurement tools applied in these studies, we could not pool the results.
      Radiological cure was not reported in any of the included studies. There was no
      significant difference in haematoma formation between the two groups (3 studies,
      189 participants: RR 0.57, 95% CI 0.17 to 1.90; I2 = 0%). Only one study reported
      patient satisfaction at three and six months; there was no significant difference
      between the two groups. AUTHORS' CONCLUSIONS: Postoperative complications as well
      as cost and time to work resumption were less in the aspiration and sclerotherapy
      group; however the recurrence rate was higher. The cure rate in short-term follow
      up was similar between the groups, however there is significant uncertainty in
      this result due to the high heterogeneity. There is a great need for further
      methodologically rigorous RCTs that assess the effectiveness of different type of
      sclerosant agents, sclerosing solution concentration and injection volume for the
      treatment of hydrocoeles. It is important that the RCTs have sufficiently large
      sample size and long follow-up period. Studies should evaluate clinical outcomes
      such as pain, recurrence, satisfaction, complications and cure using validated
      instruments. The protocols for all studies should be registered in clinical trial
      registries and the reports of these studies should conform with international
      guidelines of trial reporting such as CONSORT. Cost-effectiveness studies should
      also be undertaken.

PMID- 25391387
TI  - General thoracic surgery workforce: training, migration and practice profile in
      Brazil.
AB  - OBJECTIVES: This study is aimed at drawing the profile of the Brazilian general
      thoracic surgeon. This experience has been fruitful in other areas, helping
      attract manpower and to better serve the interests of other Societies. This is
      the first survey of this kind in Brazil and in Latin America. METHODS: An
      electronic invitation was sent to the members of the Brazilian Society of
      Thoracic Surgery to answer a web-based questionnaire and physicians potentially
      practising thoracic surgery, with 82 questions including demographic data,
      medical education, training in general and thoracic surgery, continued
      professional education, practice profile, research activities and certifications,
      participation in medical societies, income/compensation and career satisfaction.
      Quantitative and qualitative analyses are presented. RESULTS: The estimated level
      of participation was 82% (468). The mean age of the active general thoracic
      surgeon is 43.2 (range 45.3+/-11.4) years. Women comprised 8% (37) of
      respondents, and 60% (277) of the participants had graduated from public medical
      schools. Four states nationwide trained 88% (391) of the thoracic surgeons. Only
      32% (149) of the surgeons work exclusively with thoracic surgery. The public
      health system is the main provider of income for thoracic surgeons. Only 11 of 27
      states have an adequate, although poorly distributed, number of thoracic
      surgeons. CONCLUSIONS: Although Brazil has a reasonable number of general
      thoracic surgeons, inequalities in their distribution through the country arise
      as one of the most concerning problems of the speciality. The results of this
      study show that leadership actions and consistent government policies are
      required to improve work conditions and provide efficient workforce planning.

PMID- 25391388
TI  - Comparing energy sources for surgical ablation of atrial fibrillation: a Bayesian
      network meta-analysis of randomized, controlled trials.
AB  - Simplified maze procedures involving radiofrequency, cryoenergy and microwave
      energy sources have been increasingly utilized for surgical treatment of atrial
      fibrillation as an alternative to the traditional cut-and-sew approach. In the
      absence of direct comparisons, a Bayesian network meta-analysis is another
      alternative to assess the relative effect of different treatments, using indirect
      evidence. A Bayesian meta-analysis of indirect evidence was performed using 16
      published randomized trials identified from 6 databases. Rank probability
      analysis was used to rank each intervention in terms of their probability of
      having the best outcome. Sinus rhythm prevalence beyond the 12-month follow-up
      was similar between the cut-and-sew, microwave and radiofrequency approaches,
      which were all ranked better than cryoablation (respectively, 39, 36, and 25 vs
      1%). The cut-and-sew maze was ranked worst in terms of mortality outcomes
      compared with microwave, radiofrequency and cryoenergy (2 vs 19, 34, and 24%,
      respectively). The cut-and-sew maze procedure was associated with significantly
      lower stroke rates compared with microwave ablation [odds ratio <0.01; 95%
      confidence interval 0.00, 0.82], and ranked the best in terms of pacemaker
      requirements compared with microwave, radiofrequency and cryoenergy (81 vs 14,
      and 1, <0.01% respectively). Bayesian rank probability analysis shows that the
      cut-and-sew approach is associated with the best outcomes in terms of sinus
      rhythm prevalence and stroke outcomes, and remains the gold standard approach for
      AF treatment. Given the limitations of indirect comparison analysis, these
      results should be viewed with caution and not over-interpreted. 

PMID- 25391389
TI  - EACTS presidential address--the versatile beauty of the hand: mysterious,
      powerful and ingenious?.

PMID- 25391390
TI  - Exploring Stage I non-small-cell lung cancer: development of a prognostic model
      predicting 5-year survival after surgical resection?.
AB  - OBJECTIVES: Despite impressive results in diagnosis and treatment of non-small
      cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within
      5 years after surgical treatment. Identification of prognostic factors to select
      patients with a poor prognosis and development of tailored treatment strategies
      are then advisable. The aim of our study was to design a model able to define
      prognosis in patients with Stage I NSCLC, submitted to surgery with curative
      intent. METHODS: A retrospective analysis of two surgical registries was
      performed. Predictors of survival were investigated using the Cox model with
      shared frailty (accounting for the within-centre correlation). Candidate
      predictors were: age, gender, smoking habit, morbidity, previous malignancy,
      Eastern Cooperative Oncology Group performance status, clinical N stage, maximum
      standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon
      monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic
      lymphadenectomy, vascular invasion, pathological T stage, histology and
      histological grading. The final model included predictors with P < 0.20, after a
      backward selection. Missing data in evaluated predictors were multiple-imputed
      and combined estimates were obtained from 10 imputed data sets. RESULTS: Analysis
      was performed on 848 consecutive patients. The median follow-up was 48 months.
      Two hundred and nine patients died (25%), with a 5-year overall survival (OS)
      rate of 74%. The final Cox model demonstrated that mortality was significantly
      associated with age, male sex, presence of cardiac comorbidities, DLCO (%),
      SUV(max), systematic nodal dissection, presence of microscopic vascular invasion,
      pTNM stage and histological grading. The final model showed a fair discrimination
      ability (C-statistic = 0.69): the calibration of the model indicated a good
      agreement between observed and predicted survival. CONCLUSIONS: We designed an
      effective prognostic model based on clinical, pathological and surgical
      covariates. Our preliminary results need to be refined and validated in a larger
      patient population, in order to provide an easy-to-use prognostic tool for Stage
      I NSCLC patients.

PMID- 25391392
TI  - Anal fissure (chronic).
AB  - INTRODUCTION: Anal fissures are a common cause of anal pain during, and for 1 to
      2 hours after, defecation. The cause is not fully understood, but low intake of
      dietary fibre may be a risk factor. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical question: What are
      the effects of surgical treatments for chronic anal fissure? We searched:
      Medline, Embase, The Cochrane Library, and other important databases up to
      January 2014 (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 nine 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: anal advancement flap, anal
      stretch/dilation, and internal anal sphincterotomy.

PMID- 25391391
TI  - Immunological basis in the pathogenesis and treatment of bladder cancer.
AB  - The pathogenesis and transition of normal urothelium into bladder carcinoma are
      multifactorial processes. Chronic inflammation causes initiation and progression
      of the underlying pathophysiology of invasive and metastatic cancer. A dichotomy
      is observed in the role of immune cells in bladder cancer. While the immune
      response defends the host by suppressing neoplastic growth, several immune cells,
      including neutrophils, macrophages and T-lymphocytes, promote tumor development
      and progression. The levels of human neutrophil peptide-1, -2 and -3, produced by
      neutrophils, increase in bladder cancer and might promote tumor angiogenesis and
      growth. The effect of macrophages is primarily mediated by pro-inflammatory
      cytokines, IL-6 and TNF-alpha. In addition, the underlying immunological
      mechanisms of two treatments, BCG and cytokine gene-modified tumor vaccines, and
      future directions are critically discussed. 

PMID- 25391393
TI  - Improvement of gamete quality and its short-term storage: an approach for
      biotechnology in laboratory fish.
AB  - In fish, in vitro fertilization is an important reproductive tool used as first
      step for application of others biotechniques as chromosome and embryo
      manipulation. In this study, we aimed to optimize gamete quality and their short
      term storage from the yellowtail tetra Astyanax altiparanae, for future
      application in laboratory studies. Working with sperm, we evaluated the effects
      of spawning inducers (carp pituitary gland and Ovopel(r) [(D-Ala6, Pro9-NEt) -
      mGnRH+metoclopramide]) and the presence of female on sperm motility.
      Additionally, we developed new procedures for short-term storage of sperm and
      oocytes. Briefly, sperm motility was higher when male fish were treated with carp
      pituitary gland (73.1 +/- 4.0%) or Ovopel(r) (79.5 +/- 5.5%) when compared with
      the control group treated with 0.9% NaCl (55.6 +/- 27.2%; P=0.1598). Maintenance
      of male fish with an ovulating female fish also improved sperm motility (74.4 +/-
      7.4%) when compared with untreated male fish (42.1 +/- 26.1%; P=0.0018). Storage
      of sperm was optimized in modified Ringer solution, in which the sperm was kept
      motile for 18 days at 2.5 degrees C. The addition of antibiotics or oxygen
      decreased sperm motility, but partial change of supernatant and the combination
      of those conditions improve storage ability of sperm. Fertilization ability of
      oocytes decreased significantly after storage for 30, 60 90 and 120 min at 5, 10,
      15 and 20 degrees C when compared with fresh oocytes (P=0.0471), but considering
      only the stored samples, the optimum temperature was 15 degrees C. Those data
      describe new approaches to improve semen quality and gametes short-term storage
      in yellowtail tetra A. altiparanae and open new possibilities in vitro
      fertilization.

PMID- 25391394
TI  - The canine epiphyseal-derived mesenchymal stem cells are comparable to bone
      marrow derived-mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) hold great potential in cell therapy and have
      attracted increasing interests in a wide range of biomedical sciences. However,
      the scarcity of MSCs and the prolonged isolation procedure limited the clinical
      application. To address these 2 issues, we developed a method to isolate MSCs
      from bone biopsy tissues of euthanized canine body donors. Compared to the
      traditional method to isolate MSCs from aspirated bone marrow (BMSCs), the
      isolation procedure for MSCs from harvested epiphyseal cancellous bone (EMSCs)
      was less time-consuming. The isolated EMSCs had similar plastic-adherence, tri
      lineage differentiation and consistent surface marker profiles compared to BMSCs.
      We harvested BMSCs and EMSCs from 24 euthanized cases from clinics and 42
      euthanized donors from a local shelter. The successful rate for EMSC isolation is
      significantly higher compared to BMSC isolation, while the other properties of
      the isolated MSCs including the clonogenicity, proliferative potentials and
      molecular phenotypes were not discernibly different between the MSCs established
      by the two methods. In conclusion, we demonstrated a new procedure to harvest
      MSCs by bone biopsy at the epiphyseal region. This method is less time consuming
      and more reliable, and the resulting MSCs are comparable to those harvested by
      bone marrow aspiration. The combination of the two methods can greatly improve
      the efficiency to harvest MSCs. 

PMID- 25391395
TI  - Infective endocarditis of the aortic valve in a Border collie dog with patent
      ductus arteriosus.
AB  - Infective endocarditis (IE) in dogs with cardiac shunts has not been reported
      previously. However, we encountered a dog with concurrent patent ductus
      arteriosus (PDA) and IE. The dog was a 1-year-old, 13.9-kg female Border collie
      and presented with anorexia, weight loss, pyrexia (40.4  degrees C) and lameness.
      A continuous murmur with maximal intensity over the left heart base (Levine 5/6)
      was detected on auscultation. Echocardiography revealed a PDA and severe aortic
      stenosis (AS) caused by aortic-valve vegetative lesions. Corynebacterium spp. and
      Bacillus subtilis were isolated from blood cultures. The dog responded to
      aggressive antibiotic therapy, and the PDA was subsequently surgically corrected.
      After a series of treatments, the dog showed long-term improvement in clinical
      status.

PMID- 25391396
TI  - Three cases of idiopathic eosinophilic enteritis with chronic obstinate diarrhea
      in Japanese Black fattening cattle.
AB  - Eosinophilic enteritis (EOE) is a type of inflammatory bowel disease and is
      characterized clinically by chronic obstinate diarrhea. Three Japanese Black (JB)
      fattening cattle (2 males and 1 female) on different cattle farms presented with
      chronic episodic diarrhea without fever or dehydration. Soft reddish spherical
      carneous tissues (1-3 cm) were occasionally excreted within the diarrheic feces.
      Administration of antibiotics, antidiarrheal drugs and vermicides had no
      therapeutic effect, but dexamethasone improved the fecal characteristics. The
      symptoms persisted until the animals were slaughtered at 27-30 months of age.
      Histopathological examination of the intestines revealed marked eosinophilic
      infiltration in the lamina propria and submucosa. From these findings, we
      diagnosed these cattle as the first cases of EOE in JB cattle. 

PMID- 25391397
TI  - Optimization method for obtaining nearest-neighbour DNA entropies and enthalpies
      directly from melting temperatures.
AB  - MOTIVATION: Free energy nearest-neighbour (NN) thermodynamics is widely used in
      DNA biochemistry, ranging from the calculation of melting temperatures to the
      prediction of secondary structures. Methods to calculate NN parameters require
      the knowledge of total sequence entropies and enthalpies, which are not always
      available. RESULTS: Here, we implement and test a new melting temperature
      optimization method where we obtain the NN parameters directly from the
      temperatures. In this way, we bypass the constraints imposed by total sequence
      entropies and enthalpies. This enabled us to calculate the missing NN entropies
      and enthalpies for some published datasets, including salt-dependent parameters.
      Also this allowed us to combine 281 sequences from different types of melting
      temperature data for which we derived a new set of NN parameters, which have a
      smaller uncertainty and an improved predictive power. AVAILABILITY AND
      IMPLEMENTATION: C++ source code and compiled binaries for several Linux
      distributions are available from
      https://sites.google.com/site/geraldweberufmg/vargibbs and from OpenSuse build
      service at https://build.opensuse.org/package/show/home:drgweber/VarGibbs. The
      software package contains scripts and data files to reproduce all results
      presented here.

PMID- 25391398
TI  - Rclick: a web server for comparison of RNA 3D structures.
AB  - RNA molecules play important roles in key biological processes in the cell and
      are becoming attractive for developing therapeutic applications. Since the
      function of RNA depends on its structure and dynamics, comparing and classifying
      the RNA 3D structures is of crucial importance to molecular biology. In this
      study, we have developed Rclick, a web server that is capable of superimposing
      RNA 3D structures by using clique matching and 3D least-squares fitting. Our
      server Rclick has been benchmarked and compared with other popular servers and
      methods for RNA structural alignments. In most cases, Rclick alignments were
      better in terms of structure overlap. Our server also recognizes conformational
      changes between structures. For this purpose, the server produces complementary
      alignments to maximize the extent of detectable similarity. Various examples
      showcase the utility of our web server for comparison of RNA, RNA-protein
      complexes and RNA-ligand structures.

PMID- 25391399
TI  - DISOPRED3: precise disordered region predictions with annotated protein-binding
      activity.
AB  - MOTIVATION: A sizeable fraction of eukaryotic proteins contain intrinsically
      disordered regions (IDRs), which act in unfolded states or by undergoing
      transitions between structured and unstructured conformations. Over time,
      sequence-based classifiers of IDRs have become fairly accurate and currently a
      major challenge is linking IDRs to their biological roles from the molecular to
      the systems level. RESULTS: We describe DISOPRED3, which extends its predecessor
      with new modules to predict IDRs and protein-binding sites within them. Based on
      recent CASP evaluation results, DISOPRED3 can be regarded as state of the art in
      the identification of IDRs, and our self-assessment shows that it significantly
      improves over DISOPRED2 because its predictions are more specific across the
      whole board and more sensitive to IDRs longer than 20 amino acids. Predicted IDRs
      are annotated as protein binding through a novel SVM based classifier, which uses
      profile data and additional sequence-derived features. Based on benchmarking
      experiments with full cross-validation, we show that this predictor generates
      precise assignments of disordered protein binding regions and that it compares
      well with other publicly available tools.

PMID- 25391400
TI  - Hi-Corrector: a fast, scalable and memory-efficient package for normalizing large
      scale Hi-C data.
AB  - Genome-wide proximity ligation assays, e.g. Hi-C and its variant TCC, have
      recently become important tools to study spatial genome organization. Removing
      biases from chromatin contact matrices generated by such techniques is a critical
      preprocessing step of subsequent analyses. The continuing decline of sequencing
      costs has led to an ever-improving resolution of the Hi-C data, resulting in very
      large matrices of chromatin contacts. Such large-size matrices, however, pose a
      great challenge on the memory usage and speed of its normalization. Therefore,
      there is an urgent need for fast and memory-efficient methods for normalization
      of Hi-C data. We developed Hi-Corrector, an easy-to-use, open source
      implementation of the Hi-C data normalization algorithm. Its salient features are
      (i) scalability-the software is capable of normalizing Hi-C data of any size in
      reasonable times; (ii) memory efficiency-the sequential version can run on any
      single computer with very limited memory, no matter how little; (iii) fast speed
      the parallel version can run very fast on multiple computing nodes with limited
      local memory. AVAILABILITY AND IMPLEMENTATION: The sequential version is
      implemented in ANSI C and can be easily compiled on any system; the parallel
      version is implemented in ANSI C with the MPI library (a standardized and
      portable parallel environment designed for solving large-scale scientific
      problems). The package is freely available at http://zhoulab.usc.edu/Hi
      Corrector/.

PMID- 25391401
TI  - Banded gastric bypass - four years follow up in a prospective multicenter
      analysis.
AB  - BACKGROUND: The gastric bypass is the gold standard of bariatric surgery.
      Nevertheless some patients show insufficient weight loss or weight regain.
      Dilation of the pouch or the pouch outlet may be the cause. The banded gastric
      bypass tries to overcome dilation by placing an implant around the pouch or pouch
      outlet. In this study we describe our results using the GaBPTM ring system in
      banded gastric bypass operations in 3 bariatric centers. METHODS: 183 patients in
      3 bariatric reference centers received a banded gastric bypass operation using
      the GaBPTM ring system. Up to 4 years follow up was evaluated including weight
      loss and complications. RESULTS: Mean EWL after 6 Months was 60% with a mean BMI
      of 30.1 kg/m2. After one year mean EWL reached 75.3% with a mean BMI of 27 kg/m2
      (110 patients). After two and three years the EWL was 78.8% (n = 49) and 79.9% (n
      = 35). There was a mean EWL of 85% after 4 years. Thirteen patients finished a 4
      year follow up period and mean BMI after 4 years was 25.2 kg/m2. In the
      perioperative and early postoperative period there was a low complication rate
      (4.3%). Stenosis or dysphagia was observed in only one patient. There was only
      one ring related complication. CONCLUSION: Banded gastric bypass using the GaBPTM
      ring system allows good weight loss with no regain of weight in a four year
      follow up. The complication rate is low. A randomized controlled trial is
      currently underway to compare banded and conventional gastric bypass.

PMID- 25391403
TI  - Pertussis control in Australia--the current state of play.

PMID- 25391404
TI  - Australian vaccine preventable disease epidemiological review series: pertussis,
      2006-2012.
AB  - Despite pertussis vaccine being available since the 1940s and immunisation
      programs using combined diphtheria-tetanus-pertussis vaccine since the mid-1950s,
      pertussis has been the most commonly notified vaccine preventable disease in
      Australia over the past 20 years. Pertussis notification and hospitalisation data
      have been available nationally since 1993, and provide different perspectives for
      understanding epidemiological trends. This report follows on from a previous
      review of Australian pertussis epidemiology from 1995-2005 and summarises
      routinely collected notification, hospitalisation and mortality data for 2006
      2012. During the latter 7-year period, which incorporated epidemics in all
      jurisdictions, and in which acellular vaccines (as opposed to whole cell
      vaccines) were used exclusively, the average annual notification rate was more
      than 2.8 times that of the previous decade. In contrast, hospitalisation and
      mortality rates remained similar. The pattern of age-specific notification rates
      changed substantially, with cases aged 15 years or over representing 93% of total
      cases in 2006, but only 58% by 2012; the steepest increases were seen in children
      2-4 and 6-9 years of age. In South Australia, where acellular vaccines were
      introduced into the primary schedule 2 years earlier than in other jurisdictions
      except the Northern Territory, a peak in notifications among those aged 5-9 and
      10-12 years was observed earlier. Likely contributors to both the overall
      increase in notifications and changes in age distribution include increased
      diagnostic testing and more rapid waning of effectiveness following vaccination
      with acellular compared with whole cell vaccines, exacerbated by cessation of the
      18-month dose in the National Immunisation Program from 2003.

PMID- 25391402
TI  - Chromosome-wide aneuploidy study of cultured circulating myeloid progenitor cells
      from workers occupationally exposed to formaldehyde.
AB  - Formaldehyde (FA) is an economically important industrial chemical to which
      millions of people worldwide are exposed environmentally and occupationally.
      Recently, the International Agency for Cancer Research concluded that there is
      sufficient evidence that FA causes leukemia, particularly myeloid leukemia. To
      evaluate the biological plausibility of this association, we employed a
      chromosome-wide aneuploidy study approach, which allows the evaluation of
      aneuploidy and structural chromosome aberrations (SCAs) of all 24 chromosomes
      simultaneously, to analyze cultured myeloid progenitor cells from 29 workers
      exposed to relatively high levels of FA and 23 unexposed controls. We found
      statistically significant increases in the frequencies of monosomy, trisomy,
      tetrasomy and SCAs of multiple chromosomes in exposed workers compared with
      controls, with particularly notable effects for monosomy 1 [P = 6.02E-06,
      incidence rate ratio (IRR) = 2.31], monosomy 5 (P = 9.01E-06; IRR = 2.24),
      monosomy 7 (P = 1.57E-05; IRR = 2.17), trisomy 5 (P = 1.98E-05; IRR = 3.40) and
      SCAs of chromosome 5 (P = 0.024; IRR = 4.15). The detection of increased levels
      of monosomy 7 and SCAs of chromosome 5 is particularly relevant as they are
      frequently observed in acute myeloid leukemia. Our findings provide further
      evidence that leukemia-related cytogenetic changes can occur in the circulating
      myeloid progenitor cells of healthy workers exposed to FA, which may be a
      potential mechanism underlying FA-induced leukemogenesis. 

PMID- 25391405
TI  - Finding the 'who' in whooping cough: vaccinated siblings are important pertussis
      sources in infants 6 months of age and under.
AB  - OBJECTIVES: To describe the epidemiology of pertussis, and to identify changes in
      the source of pertussis in infants 6 months of age and under, during the 2008
      2012 epidemic in south metropolitan Perth. DESIGN AND SETTING: Analysis of all
      pertussis cases notified to the South Metropolitan Population Health Unit and
      recorded on the Western Australian Notifiable Infectious Disease Database over
      the study period. Information on the source of pertussis was obtained from
      enhanced surveillance data. RESULTS: Notification rates were highest in the 5-9
      years age group, followed by the 0-4 years and 10-14 years age groups. There was
      a significant increase in the proportion of known sources who were siblings from
      the early epidemic period of 2008-2010, compared with the peak epidemic period of
      2011-2012 (14.3% versus 51.4%, p = 0.002). The majority of sibling sources were
      fully vaccinated children aged 2 and 3 years. CONCLUSIONS: The incidence of
      pertussis was highest in children aged 12 years and under in this epidemic. At
      its peak, siblings were the most important sources of pertussis in infants 6
      months and younger, particularly fully vaccinated children aged 2 and 3 years.
      Waning immunity before the booster at 4 years may leave this age group
      susceptible to infection. Even if cocooning programs could achieve full
      vaccination coverage of parents and ensure all siblings were fully vaccinated
      according to national schedules, waning immunity in siblings could provide a
      means for ongoing transmission to infants. Recent evidence suggests that maternal
      antenatal vaccination would significantly reduce the risk of pertussis in infants
      3 months of age and under.

PMID- 25391406
TI  - A state-wide information campaign during a pertussis epidemic in New South Wales,
      2010.
AB  - Pertussis notifications increased dramatically in New South Wales in 2008,
      exceeding the rates in previous epidemic years. A state-wide, multi-faceted
      campaign was launched in March 2009 to provide information about pertussis
      prevention. A population-based survey was conducted using a Computer Assisted
      Telephone Interviewing facility to assess the effectiveness of sending letters to
      households with young infants. A representative sample of 1,200 adults across all
      8 area health services was interviewed between July 2009 and September 2010, with
      responses weighted against the state population. Many respondents (39.7%)
      reported receiving the letter, while fewer (29.6%) reported receiving an adult
      pertussis booster in the last year, mostly in response to General Practitioner
      advice (40.4%). Letter receipt was associated with the uptake of an adult
      pertussis booster in the past 12 months by respondents (OR 5.8; 95%CI 4.1, 8.2)
      and other adults in the household (OR 5.1; 95%CI 3.5, 7.5), as well as knowledge
      about pertussis prevention. Health providers remain crucial for vaccination
      decision making; however letters may have contributed to an increased uptake of
      pertussis booster vaccination and knowledge. Health authorities may consider
      mailing households in future pertussis epidemics as a component of a wider
      communication strategy. 

PMID- 25391407
TI  - Immunisation coverage, 2012.
AB  - This, the 6th annual immunisation coverage report, documents trends during 2012
      for a range of standard measures derived from Australian Childhood Immunisation
      Register (ACIR) data, and National Human Papillomavirus (HPV) Vaccination Program
      Register data. These include coverage at standard age milestones and for
      individual vaccines included on the National Immunisation Program (NIP) and
      coverage in adolescents and adults. The proportion of Australian children 'fully
      vaccinated' at 12, 24 and 60 months of age was 91.7%, 92.5% and 91.2%,
      respectively. For vaccines available on the NIP but not assessed during 2012 for
      'fully vaccinated' status or for eligibility for incentive payments (rotavirus
      and pneumococcal at 12 months and meningococcal C and varicella at 24 months)
      coverage varied. Although pneumococcal vaccine had similar coverage at 12 months
      to other vaccines, coverage was lower for rotavirus at 12 months (83.6%) and
      varicella at 24 months (84.4%). Although 'fully vaccinated' coverage at 12 months
      of age was lower among Indigenous children than non-Indigenous children in all
      jurisdictions, the extent of the difference varied, reaching a 15 percentage
      point differential in South Australia but only a 0.4 percentage point
      differential in the Northern Territory. Overall, Indigenous coverage at 24 months
      of age exceeded that at 12 months of age nationally and for all jurisdictions,
      but as receipt of varicella vaccine at 18 months is excluded from calculations,
      this represents delayed immunisation, with some contribution from immunisation
      incentives. The 'fully vaccinated' coverage estimates for vaccinations due by 60
      months of age for Indigenous children exceeded 90% at 91% in 2012. Unlike in
      2011, at 60 months of age, there was no dramatic variation in coverage between
      Indigenous and non-Indigenous children for individual jurisdictions. As
      previously documented, vaccines recommended for Indigenous children only,
      hepatitis A and pneumococcal vaccine, had suboptimal coverage at 60.1% and 73.1%,
      respectively, although there was a considerable improvement in coverage from
      2011, 57.7% and 68.2% respectively. On-time receipt (before 49 months of age) of
      vaccines by Indigenous children at the 60-month milestone age improved
      substantially between 2011 (19%) and 2012 (38%) but the disparity in on-time
      vaccination between Indigenous and non-Indigenous children worsened at the 60
      month age milestone from 2011 (from 1.8 to 5.4 percentage points) and remained
      the same for the 12 and 24-month age milestones. By late 2012, the percentage of
      children who received the 1st dose of DTPa vaccine dose at less than 8 weeks of
      age was greater than 50% in all but 1 jurisdiction and greater than 70% for New
      South Wales, the Australian Capital Territory and Tasmania. Further, by late
      2012, the percentage of children who received the 4th dose of DTPa vaccine dose
      at less than 4 years of age was greater than 30% in 3 jurisdictions. The
      percentage of children whose parents officially objected to vaccination in
      Australia was 1.7% and this figure varied by jurisdiction. However, there is a
      further 2.1% of children whose parents don't officially object but whose children
      have no vaccines recorded on the ACIR. Coverage data for the 3rd dose of HPV from
      the national HPV register in the school catch up program was similar to 2011 at
      71% but was substantially lower for the catch up program for females outside
      school (44%-69%), although this was an improvement from 2011. 

PMID- 25391409
TI  - National Notifiable Diseases Surveillance System, 1 April to 30 June 2014.

PMID- 25391408
TI  - Australian Enterococcal Sepsis Outcome Progamme, 2011.
AB  - From 1 January to 31 December 2011, 29 institutions around Australia participated
      in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP
      2011 was to determine the proportion of enterococcal bacteraemia isolates in
      Australia that are antimicrobial resistant, with particular emphasis on
      susceptibility to ampicillin and the glycopeptides, and to characterise the
      molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of
      the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by
      either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was
      detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical
      and Laboratory Standards Institute breakpoints (CLSI), vancomycin non
      susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium
      respectively and was predominately due to the acquisition of the vanB operon.
      Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory
      concentration at or below the CLSI vancomycin susceptible breakpoint of <= 4
      mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular
      typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE)
      pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across
      Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus
      sequence types were identified. Almost 90% of the E. faecium were identified as
      clonal complex 17 clones, of which approximately half were characterised as
      sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP
      2011 has shown that although polyclonal, enterococcal bacteraemias in Australia
      are frequently caused by ampicillin-resistant vanB E. faecium. 

PMID- 25391410
TI  - Australian childhood immunisation coverage, 1 October to 31 December cohort,
      assessed as at 31 March 2014.

PMID- 25391411
TI  - Australian Meningococcal Surveillance Programme quarterly report, 1 April to 30
      June 2014.

PMID- 25391412
TI  - Australian Sentinel Practices Research Network, 1 April to 30 June 2013.

PMID- 25391413
TI  - Invasive pneumococcal disease surveillance Australia, 1 April to 30 June 2014.

PMID- 25391414
TI  - Recommended composition of the Australian influenza vaccine for the 2015 season.

PMID- 25391415
TI  - Surveillance of adverse events following immunisation in Australia, 2012.
AB  - This report summarises Australian passive surveillance data for adverse events
      following immunisation (AEFI) reported to the Therapeutic Goods Administration
      (TGA) for 2012. It also describes reporting trends over the 13-year period 1
      January 2000 to 31 December 2012. There were 1,897 AEFI records for vaccines
      administered in 2012, a decrease of 22% from 2,417 in 2011. The decrease in 2012
      compared with 2011 was mainly attributable to a drop in the reports following
      receipt of the 23-valent pneumococcal polysaccharide vaccine (405 reduced to
      133). However, reporting rates for some other vaccines such as rotavirus and
      varicella vaccines were higher in 2012 than 2011. Although an increase was
      observed in estimated reporting rates for rotavirus and varicella in children
      aged < 7 years in 2012 compared with 2011, it was not statistically significant.
      There were 370 AEFI records (37.2 per 100,000 doses) for the pneumococcal
      conjugate vaccine in 2012, which was fewer than in 2011 (43.4 per 100,000 doses).
      The most commonly reported reactions were injection site reactions (40%), fever
      (22%), allergic reactions (19%) and rash (10%). Only 7% of all the reported
      adverse events were categorised as serious. There were 2 reports of death, which
      were investigated by the TGA and no clear causal relationship with vaccination
      was found. 

PMID- 25391416
TI  - Test yourself: question - lateral leg pain.

PMID- 25391417
TI  - Erratum to: MRI pattern of arthritis in systemic lupus erythematosus: a
      comparative study with rheumatoid arthritis and healthy subjects.

PMID- 25391418
TI  - Does Salter innominate osteotomy predispose the patient to acetabular
      retroversion in adulthood?
AB  - BACKGROUND: Salter innominate osteotomy has been identified as an effective
      additional surgery for the dysplastic hip. However, because in this procedure,
      the distal segment of the pelvis is displaced laterally and anteriorly, it may
      predispose the patient to acetabular retroversion. The degree to which this may
      be the case, however, remains incompletely characterized. QUESTIONS/PURPOSES: We
      asked, in a group of pediatric patients with acetabular dysplasia who underwent
      Salter osteotomy, whether the operated hip developed (1) acetabular retroversion
      compared with contralateral unaffected hips; (2) radiographic evidence of
      osteoarthritis; or (3) worse functional scores. (4) In addition, we asked whether
      femoral head deformity resulting from aseptic necrosis was a risk factor for
      acetabular retroversion. METHODS: Between 1971 and 2001, we performed 213 Salter
      innominate osteotomies for unilateral pediatric dysplasia, of which 99 hips (47%)
      in 99 patients were available for review at a mean of 16 years after surgery
      (range, 12-25 years). Average patient age at surgery was 4 years (range, 2-9
      years) and the average age at the most recent followup was 21 years (range, 18-29
      years). Acetabular retroversion was diagnosed based on the presence of a positive
      crossover sign and prominence of the ischial spine sign at the final visit. The
      center-edge angle, acetabular angle of Sharp, and acetabular index were measured
      at preoperative and final visits. Contralateral unaffected hips were used as
      controls, and statistical comparison was made in each patient. Clinical findings,
      including Harris hip score (HHS) and the anterior impingement sign, were recorded
      at the final visit. RESULTS: Patients were no more likely to have a positive
      crossover sign in the surgically treated hips (20 of 99 hips [20%]) than in the
      contralateral control hips (17 of 99 hips [17%]; p = 0584). In addition, the
      percentage of positive prominence of the ischial spine sign was not different
      between treated hips (22 of 99 hips [22%]) and contralateral hips (18 of 99 hips
      [18%]; p = 0.256). Hips that had a positive crossover or prominence of the
      ischial spine sign in the operated hips were likely also to have a positive
      crossover sign or prominence of the ischial spine sign in the unaffected hips (16
      of 20 hips [80%] crossover sign, 17 of 22 hips [77%] prominence of the ischial
      spine sign). At the final visit, five hips (5%) showed osteoarthritic change; one
      of the five hips (20%) showed positive crossover and prominence of the ischial
      spine signs, and the remaining four hips showed negative crossover and prominence
      of the ischial spine signs. There was no significant difference in HHS between
      the crossover-positive and crossover-negative patient groups nor in the
      prominence of the ischial spine-positive and prominence of the ischial spine
      negative patient groups (crossover sign, p = 0.68; prominence of the ischial
      spine sign, p = 0.54). Hips with femoral head deformity (25 of 99 hips [25%])
      were more likely to have acetabular retroversion compared with hips without
      femoral-head deformity (crossover sign, p = 0.029, prominence of the ischial
      spine sign, p = 0.013). CONCLUSIONS: Our results suggest that Salter innominate
      osteotomy does not consistently cause acetabular retroversion in adulthood. We
      propose that retroversion of the acetabulum is a result of intrinsic development
      of the pelvis in each patient. A longer-term followup study is needed to
      determine whether retroverted acetabulum after Slater innominate osteotomy is a
      true risk factor for early osteoarthritis. Femoral head deformity is a risk
      factor for subsequent acetabular retroversion. LEVEL OF EVIDENCE: Level III,
      therapeutic study.

PMID- 25391419
TI  - Validation of the Clutter Image Rating in older adults with hoarding disorder.
AB  - BACKGROUND: The Clutter Image Rating (CIR) was created to meet a gap in the
      research on compulsive hoarding: how to ascertain clutter level in an
      individual's home without a home visit, as not all clinicians have the ability to
      conduct a home visit. The CIR has proven itself to be both reliable and valid for
      use in adults with compulsive hoarding symptoms. However, there is currently a
      dearth of information on performance of the CIR in older adults diagnosed with
      hoarding disorder (HD). Because older adults have increased medical issues,
      including fall risks, evaluating the level of clutter in the house is especially
      critical in geriatric populations. METHOD: The current study was an investigation
      of the reliability and validity of the CIR in assessing late life HD. The
      internal consistency, convergent and divergent validity, and norms of the CIR
      were investigated in a large geriatric HD sample and compared with a midlife
      sample of individuals with HD. Criterion validity of the CIR was investigated
      through the comparison of participant ratings conducted in the clinic and
      clinician ratings conducted in the home. RESULTS: The current study found similar
      levels of reliability and validity in a late life sample as in previous studies
      conducted in mid-life adults. CONCLUSIONS: Unlike previous studies, the current
      study did not find a significant relationship between the CIR and the non-clutter
      related subscales of the Savings Inventory-Revised. The CIR appears to be both
      reliable and valid for assessing clutter levels in older adults diagnosed with
      HD.

PMID- 25391420
TI  - Demonstration of biosimilarity, extrapolation of indications and other challenges
      related to biosimilars in Europe.
AB  - The regulatory framework for biosimilars was established across Europe in 2005
      based on the concept of biosimilarity. This legislation secures the
      manufacturing, evaluation, and market authorization (MA) of high-quality safe and
      efficacious biopharmaceuticals that are highly similar to their reference
      medicinal product (biosimilars). Demonstration of biosimilarity is documented by
      full-scale comparability exercises between the biosimilar and the reference
      product at quality, preclinical, and clinical level. However, the complexity,
      diversity, and heterogeneity of biosimilars, both in structure and manufacturing,
      combined with the scientific knowledge accumulated in biotechnological analysis
      of recombinant therapeutic proteins requires continuous improvement of the
      regulatory framework based on the evolution and experience gained in this field.
      This current opinion article presents the concept of biosimilarity, discusses the
      extrapolation of indications that is acceptable based on a case-by-case basis by
      CHMP/EMA and uncovers other challenges lying ahead in the development of
      biosimilars. Biosimilars are still quite 'young' products that require worldwide
      attention. 

PMID- 25391421
TI  - The polymorphism MMP1 -1607 (1G>2G) is associated with a significantly increased
      risk of cancers from a meta-analysis.
AB  - Growing evidences show that matrix metalloproteinase 1 (MMP1) plays important
      roles in tumorigenesis and cancer metastasis. MMP1 -1607 1G>2G is a single
      nucleotide polymorphism in the promoter region of MMP1 and affects MMP1
      production. Analysis of previous studies on the association of -1607 1G>2G
      polymorphism with different cancer types remained to be illustrated. To further
      assess the effect of -1607 1G>2G polymorphism on cancer risk, we performed this
      meta-analyses, up to September 8, 2014, of 10,640 cases and 10,915 controls from
      42 published case-control designed studies. Statistical analyses were performed
      using STATA 11.0 software. Crude odds ratios (ORs) with 95% confidence intervals
      (CIs) were used to assess the strength of associations. ORs with 95% CIs for the
      polymorphism MMP1 -1607 1G>2G and cancer were estimated using fixed and random
      effects models when appropriate. Significantly increased risks were found in
      overall under the models of 2G vs.1G, 2G2G vs. 1G1G, 2G2G/1G2G vs. 1G1G, and 2G2G
      vs. 2G1G/1G1G. Significantly elevated risks were observed in colorectal adenoma
      under the models of 2G vs. 1G, 2G2G vs. 1G1G, 2G2G/1G2G vs. 1G1G, and 2G2G vs.
      2G1G/1G1G and lung cancer and head and neck cancer under the models of 2G vs. 1G.
      We found that significantly elevated risks were observed in Asian population and
      hospital-based studies in most comparison models tested. Thus, this meta-analysis
      indicates that the polymorphism MMP1 -1607 1G>2G is significantly associated with
      a significantly increased risk of cancers and may provide evidence-based medical
      certificate to study the cancer susceptibility.

PMID- 25391422
TI  - Up-regulation of 14-3-3zeta expression in intrahepatic cholangiocarcinoma and its
      clinical implications.
AB  - The 14-3-3 proteins are highly conserved molecules that are involved in many
      vital biologic processes and are associated with the progression of cancer. The
      role of 14-3-3zeta, a dimeric isoform of 14-3-3, in intrahepatic
      cholangiocarcinoma (ICC) was investigated in this study. The expression of 14-3
      3zeta in tumour samples from patients with ICC was examined by Western blot and
      immunohistochemistry, and the correlation between its expression and various
      clinicopathological features was determined. Then, the capacity for invasion,
      migration and proliferation as well as the expression of epithelial-mesenchymal
      transition (EMT)-related markers in ICC cells were assessed after 14-3-3zeta
      depletion. Finally, the prognostic significance of 14-3-3zeta in patients with
      ICC was further evaluated by Kaplan-Meier and Cox regression analyses. The
      expression of 14-3-3zeta was significantly higher in ICC tissues compared to
      peritumoural tissues. High expression of 14-3-3zeta positively correlated with
      lymphatic metastasis and tumour-node-metastasis (TNM) stage. The inhibition of 14
      3-3zeta expression was able to impair the invasion, migration and proliferation
      of ICC cells in vitro. The expression of 14-3-3zeta was significantly correlated
      with the expression of the EMT-related markers snail and E-cadherin in ICC
      samples. Moreover, the down-regulation of 14-3-3zeta also decreased the
      phosphorylation of extracellular signal-regulated kinase (ERK) in ICC cells.
      Clinically, patients with ICC with high 14-3-3zeta expression demonstrated a poor
      prognosis in terms of a short overall survival and a high recurrence rate of the
      disease. A multivariate analysis revealed that 14-3-3zeta overexpression was an
      independent prognostic indicator for patients with ICC. 14-3-3zeta may enhance
      the invasive and proliferative capacity of tumour cells and thus prompt the
      progression of ICC via the activation of ERK signalling and the induction of EMT.
      The overexpression of 14-3-3zeta may be used as a prognostic biomarker and
      therapeutic target in patients with ICC. 

PMID- 25391423
TI  - Lymphovascular invasion and histologic grade are associated with specific genomic
      profiles in invasive carcinomas of the breast.
AB  - Lymphovascular invasion (LVI) and histologic grade are clinical parameters of
      high prognostic value in breast cancer and indicate the level of tumor
      aggressiveness. Many studies have focused on the association of breast cancer
      subtypes with gene expression and chromosomal profiles, but considerably less
      genomic information is available regarding traditional prognostic factors such as
      histologic grade and LVI. We studied by array-CGH a group of 57 invasive ductal
      carcinomas of the breast to outline the DNA copy number aberration (CNA) profile
      linked to high histologic grades and LVI. Selected CNAs were validated using real
      time quantitative PCR (qPCR). Furthermore, gene expression analysis was performed
      in a subset of 32 of these tumors, and findings were integrated with array-CGH
      data. Our findings indicated an accumulation of genomic alterations in high-grade
      breast tumors compared to low-grade samples. Grade III tumors showed higher
      number of CNAs and larger aberrations than low-grade tumors and displayed a wide
      range of chromosomal aberrations, which were mainly 5p, 8q, 10p, 17q12, and 19
      gains, and 3p, 4, 5q proximal, 9p, 11p, 18q, and 21 losses. The presence of LVI,
      a well-established prognostic marker, was not significantly associated with
      increased genomic instability in comparison to breast tumors negative for LVI,
      considering the total number of chromosomal alterations. However, a slightly
      increase in the frequency of specific alterations could be detected in LVI
      positive group, such as gains at 5p, 16p, 17q12, and 19, and losses at 8p, 11q,
      18q, and 21. Three newly reported small-scale rearrangements were detected in
      high-risk tumors (LVI-positive grade III) harboring putative breast cancer genes
      (amplicons at 4q13.3 and 11p11.2, and a deletion at 12p12.3). Furthermore, gene
      expression analysis uncovered networks highlighting S100A8, MMP1, and MED1 as
      promising candidate genes involved in high-grade and LVI-positive tumors. In
      summary, a group of genomic regions could be associated with high-risk tumors,
      and expression analysis pinpointed candidate genes deserving further
      investigation. The data has shed some light on the molecular players involved in
      two highly relevant prognostic factors and may further add to the understanding
      of the mechanisms of breast cancer aggressiveness.

PMID- 25391424
TI  - Plasma long noncoding RNA protected by exosomes as a potential stable biomarker
      for gastric cancer.
AB  - Long intergenic non-protein-coding RNA 152 (LINC00152) is one of the long
      noncoding RNAs (lncRNAs) abnormally expressed in gastric cancer tissues. However,
      its value in the diagnosis of gastric cancer is unclear. The aim of this study is
      to evaluate the clinical significance of plasma LINC00152 as a biomarker in the
      screening of gastric cancer and to explore the possible mechanism underling its
      stable existence in blood. We analyzed the levels of plasma LINC00152 in patients
      with gastric cancer and gastric epithelial dysplasia and healthy controls using
      quantitative reverse transcription polymerase chain reaction and then confirmed
      by sequencing. We also compared its levels in paired preoperative and
      postoperative plasma samples. In addition, we compared the levels of LINC00152 in
      plasma and in exosomes, which were extracted from the same plasma and confirmed
      by transmission electron microscopy. The levels of plasma LINC00152 were
      significantly elevated in gastric cancer patients compared with healthy controls.
      The sensitivity and specificity of plasma LINC00152 in the diagnosis of gastric
      cancer were 48.1 and 85.2%, respectively. There were no significant differences
      of LINC00152 levels between gastric epithelial dysplasia patients and healthy
      controls. LINC00152 levels in preoperative plasma samples were lower than those
      in postoperative ones. There were also no differences between LINC00152 levels in
      plasma and in exosomes. All these results suggested that LINC00152 can be
      detected in plasma, and one of the possible mechanisms of its stable existence in
      blood was protected by exosomes. It has the possibility to be applied in gastric
      cancer diagnosis as a novel blood-based biomarker.

PMID- 25391425
TI  - MiR-451 inhibits cell growth and invasion by targeting CXCL16 and is associated
      with prognosis of osteosarcoma patients.
AB  - Recent studies have shown that microRNA-451 (miR-451) was significantly decreased
      in osteosarcoma tissues and was identified as a tumor suppressor in other types
      of human cancers. However, its clinical significance and molecular mechanisms in
      osteosarcoma are still not well understood. MiR-451 levels are evaluated by
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) in
      osteosarcoma cell lines and in 68 pairs of osteosarcoma and adjacent noncancerous
      tissues. Then, the associations of miR-451 expression with clinicopathological
      features of patients were determined. The effects of miR-451 in osteosarcoma
      cells were examined by MTT and Matrigel invasion assay. The functional target of
      miR-451 were determined by bioinformatics analysis and validated by luciferase
      reporter analyses and Western blot assay. Our results showed that the expression
      of miR-451 was significantly downregulated in osteosarcoma tissues compared with
      corresponding noncancerous tissues (P < 0.01). Particularly, statistical analysis
      of primary human osteosarcoma indicated that decreased expression of miR-451 was
      correlated with metastasis and recurrence. Moreover, the miR-451 force-expression
      suppressed cell proliferation and invasion in vitro. Based on bioinformatics
      analysis, we found that chemokine ligand 16 (CXCL16) was identified as a direct
      functional target of miR-451. Consistent with the effects of miR-451, silencing
      CXCL16 could phenocopy the effects of miR-451 on phenotypes of osteosarcoma
      cells. Furthermore, CXCL16 expression was upregulated in osteosarcoma tissues and
      inversely associated with miR-451 in human osteosarcoma tissues. Our data reveal
      a downregulated expression of miR-451 in osteosarcoma tissues, which is inversely
      associated with CXCL16 levels. These observations demonstrated that miR-451 may
      play an important role in tumor growth and metastasis in osteosarcoma. 

PMID- 25391426
TI  - Down-regulation of LATS2 in non-small cell lung cancer promoted the growth and
      motility of cancer cells.
AB  - LATS2 (Large tumor suppressor) has been reported to be dys-regulated in several
      cancer types. However, its function in non-small cell lung cancer (NSCLC) remains
      poorly understood. Here, it was found that the expression level of LATS2 was
      decreased in NSCLC tissues. Moreover, forced expression of LATS2 in NSCLC cells
      inhibited cell growth and migration, while knockdown of the expression of LATS2
      promoted the tumorigenicity of NSCLC cells. Mechanistically, LATS2 was found to
      negatively regulate NF-kappaB signaling in NSCLC cells. Taken together, our study
      suggested that down-regulation of LATS2 was very important in the progression of
      NSCLC, and restoring the function of LATS2 might be a promising therapeutic
      strategy for NSCLC. 

PMID- 25391427
TI  - Associations of polymorphisms in the bone morphogenetic protein-2 gene with risk
      and prognosis of osteosarcoma in a Chinese population.
AB  - Osteosarcoma is the most common type of bone cancer in adolescence. Bone
      morphogenetic protein-2 (BMP-2) plays important roles in the development of bone
      and cartilage and in inhibiting the tumorigenicity of cancer stem cells in human
      osteosarcoma cell line. The aim of this study was to examine whether
      polymorphisms in the BMP2 gene are associated with osteosarcoma risk and
      prognosis in Chinese population. Five single nucleotide polymorphisms (SNP) in
      the BMP2 gene were genotyped in a case-control study, including 203 osteosarcoma
      patients and 406 cancer-free controls. We found that rs3178250 TT genotype was
      associated with significant increased osteosarcoma risk (age-adjusted odds ratio
      (OR) = 2.06, 95% confidence intervals (CI) of 1.23-3.45) compared with CC
      genotype. Subjects carrying the AA genotype of rs1005464 had significant
      decreased cancer risk (age-adjusted OR = 0.44, 95% CI of 0.23-0.85) compared with
      those carrying the GG genotype. Haplotype analysis also showed that carriers of
      the G-T-T-G and A-T-T-G haplotypes (rs235764-rs3178250-rs235768-rs1005464) had
      significant increased risks of osteosarcoma (age-adjusted OR = 1.85, 95% CI of
      1.28-2.66 and age-adjusted OR = 1.51, 95% CI of 1.06-2.16) compared with the G-C
      T-A haplotype carriers. Besides, rs1005464 was an independent prognostic factor
      for osteosarcoma patients (GA vs. GG: age-adjusted hazard radio (HR) = 0.60, 95%
      CI of 0.36-0.99). Our data suggest that genetic mutations in the BMP2 gene are
      associated with osteosarcoma risk and prognosis in a Chinese population.

PMID- 25391428
TI  - Downregulation of RIP140 in hepatocellular carcinoma promoted the growth and
      migration of the cancer cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies with a poor
      response to chemotherapy. It is very important to identify novel diagnosis
      biomarkers and therapeutic targets. RIP140, a regulator of estrogen receptor,
      recently has been found to be involved in the tumorigenesis. However, its
      function in the progression of HCC remains poorly understood. Here, we found that
      the expression of RIP140 was downregulated in the HCC tissues. Moreover,
      overexpression of RIP140 in HCC cells inhibited cell proliferation and migration,
      while downregulation of RIP140 promoted the tumorigenicity of HCC cells in vitro
      and in vivo. Mechanistically, RIP140 interacted with beta-catenin and negatively
      regulated beta-catenin/TCF signaling. Taken together, our study suggests the
      suppressive roles of RIP140 in the pathogenesis of HCC. 

PMID- 25391429
TI  - PX-12 induces apoptosis in Calu-6 cells in an oxidative stress-dependent manner.
AB  - PX-12 (1-methylpropyl 2-imidazolyl disulfide) as a thioredoxin (Trx) inhibitor
      has an anti-tumor effect. However, there is no report about the toxicological
      effect of PX-12 on lung cancer cells. Here, we investigated the anti-growth
      effects of PX-12 on Calu-6 lung cancer cells in relation to reactive oxygen
      species (ROS) and glutathione (GSH) levels. PX-12 induced the growth inhibition
      of Calu-6 cells with IC50 of nearly 3 MUM at 72 h. In contrast, PX-12 did not
      affect the growth of human small airway epithelial cells (HSAECs). Cell cycle
      distribution analysis indicated that PX-12 significantly induced a G2/M phase
      arrest in Calu-6 cells. PX-12 also increased the number of annexin V-FITC
      positive cells in Calu-6 cells. All the tested caspase inhibitors markedly
      prevented Calu-6 cell death induced by PX-12. With regard to ROS and GSH levels,
      PX-12 increased ROS levels containing O2(.-) in Calu-6 cells and induced the
      depletion of GSH. N-acetyl cysteine (NAC), which is a well-known antioxidant,
      significantly reduced O2(.-) level in PX-12-treated Calu-6 cells and prevented
      apoptosis and GSH depletion in these cells. In conclusion, it is the first report
      that PX-12 inhibited the growth of Calu-6 cells via a G2/M phase arrest as well
      as apoptosis, which effect was related to the intracellular increases in ROS
      levels.

PMID- 25391430
TI  - Serum transforming growth factor-beta1 levels may have predictive and prognostic
      roles in patients with gastric cancer.
AB  - Transforming growth factor-beta1 (TGF-beta1) plays an important role in the
      pathogenesis of multiple malignancies, and also, its expression strongly affects
      the outcomes of cancer patients. The objective of this study was to determine the
      clinical significance of the serum levels of TGF-beta1 in gastric cancer
      patients. A total of 63 patients with a pathologically confirmed diagnosis of
      gastric cancer were enrolled into this study. Serum TGF-beta1 concentrations were
      determined by the solid-phase sandwich ELISA method. Thirty healthy age- and sex
      matched controls were included in the analysis. The median age at diagnosis was
      62 years, range 28 to 82 years. There was no significant difference in baseline
      serum TGF-beta1 levels between gastric cancer patients and the healthy control
      group (p = 0.08). The known clinical variables including age of patient, gender,
      site of lesion, histology, histological grade, stage of disease, and serum levels
      of lactate dehydrogenase (LDH), CEA, and carbohydrate antigen (CA) 19.9 were not
      found to be correlated with serum TGF-beta1 concentrations (p > 0.05). However,
      the chemotherapy-responsive patients had higher serum TGF-beta1 levels compared
      with chemotherapy-unresponsive ones (median values 330.50 v 49.54 pg/mL,
      respectively, p = 0.01). Moreover, patients with elevated serum TGF-beta1
      concentrations had significantly favorable overall survival compared with those
      with lower levels (median 71.1 v 39.9 weeks, respectively, p = 0.04). In
      conclusion, serum levels of TGF-beta1 may have predictive and prognostic roles in
      patients with gastric cancer.

PMID- 25391432
TI  - Community health worker interventions to improve access to health care services
      for older adults from ethnic minorities: a systematic review.
AB  - BACKGROUND: The health status of older adults belonging to ethnic minorities in
      Western countries is an important public issue because their health is often less
      favourable than that of older adults from the majority population. In addition,
      the number of older adults belonging to ethnic minorities is increasing rapidly
      in Western countries. The introduction of community health workers (CHWs) has
      proven to be successful in addressing health disparities among ethnic minorities;
      however, an overview of CHW's benefits for older adults is absent in the
      literature. We reviewed the literature to explore whether CHWs are also effective
      in improving the health and the delivery of health care services to ethnic
      minority older adults in Western countries. METHODS: We searched the PubMed
      database (2002-Present) for RCTs published on the use of CHWs in Western
      countries. RESULTS: Out of the 729 studies identified, seven studies met our
      inclusion criteria. The effectiveness of the implementation of CHW programmes in
      older adults belonging to ethnic minorities is not univocal. In two studies, we
      found no significant differences. In five studies, we found some positive
      effects. We did not find negative effects in any of the studies. For better
      interpretation of the results, effect ratios (ERs) were calculated as the number
      of positive findings divided by the total number of measured findings.
      Substantial effects on the access to care (mean ER = 0.58) and on health
      behaviour (mean ER = 0.45) were found. The mean ER for health outcomes was
      considerably lower (mean ER = 0.17). CONCLUSION: We found indications that CHWs
      serve as a means of improving health care use and health behaviour and, to a
      lesser extent, health outcomes among ethnic minority older adults. Further
      research is required to draw more solid conclusions on the effectiveness of CHW
      interventions in this target group. This is particularly important for Western
      countries in which the number of ethnic minority older adults has increased
      significantly because their health status is mostly unfavourable and their access
      to health care services is often limited.

PMID- 25391433
TI  - Acrylamide analysis in food by liquid chromatographic and gas chromatographic
      methods.
AB  - Acrylamide (AA) is a compound classified as carcinogenic to humans by the
      International Agency for Research on Cancer. It was first discovered to be
      present in certain heated processed food by the Swedish National Food
      Administration (SNFA) and University of Stockholm in early 2002. The major
      pathway for AA formation in food is the Maillard reaction between reducing sugar
      and the amino acid asparagine at high temperature. Since the discovery of AA's
      presence in food, many analytical methods have been developed for determination
      of AA contents in different food matrices. Also, several studies have been
      conducted to develop extraction procedures for AA from difficult food matrices.
      AA is a small, highly polar molecule, which makes its extraction and analysis
      challenging. Many articles and reviews have been published dealing with AA in
      food. The aim of the review is to discuss AA formation in food, the factors
      affecting AA formation and removal, AA exposure assessment, AA extraction and
      cleanup from food samples, and analytical methods used in AA determination, such
      as high-performance liquid chromatography (HPLC) and gas chromatography (GC).
      Special attention is given to sample extraction and cleanup procedures and
      analytical techniques used for AA determination. 

PMID- 25391431
TI  - Effect of acupuncture treatment on vascular cognitive impairment without
      dementia: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Vascular cognitive impairment, no dementia (VCIND) is a condition at
      risk for future dementia and should be the target of preventive strategies.
      Preliminary evidence suggests that acupuncture may be a clinically effective
      intervention for people with early-stage vascular cognitive impairment. We will
      do a multicenter, 6-month, drug-controlled, nonblinded, randomized, parallel
      group trial to determine whether acupuncture is effective for improving cognitive
      function and quality of life for patients with VCIND. METHODS/DESIGN: A total of
      216 eligible patients will be recruited and randomly assigned acupuncture for two
      sessions/week (n = 108) or citicoline 300 mg/day (n = 108) in a multicenter, 6
      month trial. The primary endpoint is cognition (Alzheimer's Disease Assessment
      Scale, Cognitive Subscale (ADAS-cog)). Secondary endpoints include assessments of
      activities of daily living and behavioral symptoms (Clock Drawing Test (CDT),
      Activities of Daily Living (ADL) and Instrumental Activities of Daily Living
      scale (IADL)). DISCUSSION: This will be the first large-scale trial specifically
      evaluating acupuncture therapy in VCIND. If the study confirms the effectiveness
      and safety of acupuncture treatment, it will be important to examine how the
      acupuncture approach could most effectively be integrated into the provision of
      routine healthcare. TRIAL REGISTRATION: This study is registered as an
      International Standard Randomised Controlled Trial on 17 January 2014, number
      ISRCTN 82980206.

PMID- 25391434
TI  - New trends in sample preparation techniques for environmental analysis.
AB  - Environmental samples include a wide variety of complex matrices, with low
      concentrations of analytes and presence of several interferences. Sample
      preparation is a critical step and the main source of uncertainties in the
      analysis of environmental samples, and it is usually laborious, high cost, time
      consuming, and polluting. In this context, there is increasing interest in
      developing faster, cost-effective, and environmentally friendly sample
      preparation techniques. Recently, new methods have been developed and optimized
      in order to miniaturize extraction steps, to reduce solvent consumption or become
      solventless, and to automate systems. This review attempts to present an overview
      of the fundamentals, procedure, and application of the most recently developed
      sample preparation techniques for the extraction, cleanup, and concentration of
      organic pollutants from environmental samples. These techniques include: solid
      phase microextraction, on-line solid phase extraction, microextraction by packed
      sorbent, dispersive liquid-liquid microextraction, and QuEChERS (Quick, Easy,
      Cheap, Effective, Rugged and Safe). 

PMID- 25391435
TI  - Determination of the mineral composition of foods by infrared spectroscopy: a
      review of a green alternative.
AB  - The determination of mineral composition of foods involves, in most cases, the
      use of long and tedious sample preparation, which consumes acids and reagents and
      sometimes requires the use of expensive instrumentation. This is the main reason
      for the search for direct analytical procedures, based on the use of infrared
      sample spectra and chemometrics, to model the signals in order to determine the
      presence of essential and trace toxic elements in foods. The state-of-the-art of
      the research in this field has been established in the present review article
      from the critical evaluation of articles available in the literature. Chemometric
      methods employed and their validation, together with a discussion about the
      different techniques used for signal acquisition, were evaluated for their
      ability to predict new sample composition. 

PMID- 25391436
TI  - fNIRS suggests increased effort during executive access in ecstasy polydrug
      users.
AB  - BACKGROUND: Ecstasy use is associated with cognitive impairment, believed to
      result from damage to 5-HT axons. Neuroimaging techniques to investigate
      executive dysfunction in ecstasy users provide a more sensitive measure of
      cognitive impairment than behavioural indicators. The present study assessed
      executive access to semantic memory in ecstasy polydrug users and non-users.
      METHODS: Twenty ecstasy polydrug users and 20 non-user controls completed an oral
      variant of the Chicago Word Fluency Test (CWFT), whilst the haemodynamic response
      to the task was measured using functional near-infrared spectroscopy (fNIRS).
      RESULTS: There were no between-group differences in many background measures
      including measures of sleep and mood state (anxiety, arousal, hedonic tone). No
      behavioural differences were observed on the CWFT. However, there were
      significant differences in oxy-Hb level change at several voxels relating to the
      left dorsolateral prefrontal cortex (DLPFC) and right medial prefrontal cortex
      (PFC) during the CWFT, indicating increased cognitive effort in ecstasy users
      relative to controls. Regression analyses showed that frequency of ecstasy use,
      total lifetime dose and amount used in the last 30 days was significant
      predictors of oxy-Hb increase at several voxels after controlling for alcohol and
      cannabis use indices. CONCLUSION: The results suggest that ecstasy users show
      increased activation in the PFC as a compensatory mechanism, to achieve
      equivalent performance to non-users. These findings are in agreement with much of
      the literature in the area which suggests that ecstasy may be a selective
      serotonin neurotoxin in humans.

PMID- 25391437
TI  - [Management of multiresistant pathogens in urology].
AB  - Epidemiological data from recent years confirm the increasing problem of
      antimicrobial resistance not only for healthcare-associated, gram-positive
      pathogens but also for gram-negative bacteria. In particular, the progressive
      increase in resistance to third generation cephalosporins and carbapenems in
      Enterobacteriaceae is of great concern. With its contribution to infectious
      morbidity, mortality and financial costs to healthcare systems worldwide,
      multidrug-resistant pathogens emerge more and more as a public health issue of
      substantial socioeconomic importance. The Commission for Hospital Hygiene and
      Infection Prevention (KRINKO) at the Robert Koch Institute (RKI) decided to
      formulate novel definitions for multidrug-resistance in order to develop hygiene
      measures for infections and colonization with multidrug-resistant gram-negative
      bacilli.

PMID- 25391438
TI  - [Oral bioavailability of oncological preparations: the intake conditions are
      often decisive].
AB  - The oral administration of pharmaceuticals plays an important role due to the
      many advantages, such as the simple administration and the associated high
      acceptance by patients. For modern oncological therapy in particular, the
      frequently encountered distribution of drug intake over morning, midday and
      evening is insufficient. Due to the sometimes highly significant food effect, the
      time of intake relative to mealtimes becomes of substantial importance. According
      to current knowledge the safest way to achieve as constant as possible resorption
      is to maintain strict rules with respect to intake times relative to food intake.
      Oral therapy with oncological drugs with pronounced food effects still raises the
      question how much the resorption is affected by simultaneous therapy with
      opioids. 

PMID- 25391439
TI  - [Detection of lymphovascular invasion in urothelial carcinoma of the bladder
      through D2-40 immunostaining].
AB  - BACKGROUND: Lymphovascular invasion (LVI) represents a surrogate marker for
      micrometastatic urothelial carcinoma of the bladder (UCB). OBJECTIVES: We
      evaluated whether D2-40 immunhistochemistry (IHC) alters detection of LVI when
      compared to conventional HE (hematoxylin-eosin) staining of UCB specimens in a
      blinded fashion. MATERIAL AND METHODS: HE- and D2-40-IHC-stained representative
      sections of 80 patients after radical cystectomy (RC) were re-reviewed. LVI
      detection rates were recorded and compared after blinded evaluation. RESULTS: LVI
      was present in 53 patients (66.3%) in HE-stained sections and in 44 patients
      (55%) in D2-40 stainings. In 13 patients, LVI (16.3%) was found in HE stained
      sections but not confirmed when IHC was applied (false positive when using IHC as
      a reference standard). D2-40 IHC identified LVI in 4 additional patients (5%) who
      were classified as LVI negative in conventional HE staining (false negative). 52
      patients (65%) were lymph node negative (pN0), 21 of whom (40.4%) were LVI
      positive in conventional HE sections and 16 of whom (30.8%) were LVI positive in
      IHC. In 9 pN0 patients (17.3%), LVI was diagnosed in HE sections but not
      confirmed by IHC (false positive). D2-40 IHC identified LVI in 4 additional
      patients (7.7%) who were node negative and classified as LVI negative in
      conventional HE staining (false negative). In patients who experienced recurrence
      (n=35) and who were classified as pN0 at the time of RC, HE staining resulted
      both in false-positive (n=2; 5.7%) and false-negative (n=3; 8.6%) findings.
      CONCLUSION: Different detection rates of LVI were observed when using IHC with D2
      40 in UCB patients compared to conventional HE staining. The routine use of D2-40
      IHC should be considered in clinical trial design to improve risk stratification
      of pN0 patients after RC.

PMID- 25391440
TI  - [Patterns of care of patients with localized prostate cancer in Germany: a health
      care study with focus on active surveillance].
AB  - BACKGROUND: To date, evidence on active surveillance (AS) is restricted to
      protocol-based studies and the current practice pattern outside medical centers
      is unknown. OBJECTIVES: The goal of this work was to capture the current
      treatment pattern of AS for localized prostate cancer (PCa) in patients managed
      by office-based urologists in Germany. MATERIALS AND METHODS: Our cohort
      consisted of 361 patients included in the AS arm of the HAROW (Hormonal
      Treatment, Active Surveillance, Radiation Therapy, OP, Watchful Waiting) study,
      an observational health service study in Germany. Descriptive characteristics and
      active-treatment-free survival (ATFS), surgical outcomes, and triggers for active
      treatment were assessed. RESULTS: Currently, only 15% of all patients with
      localized PCa were treated with AS. At baseline, 83% and 58% of all AS patients
      met the Chism and PRIAS low-risk criteria, respectively. After a median follow-up
      of 24 months, no systemic progression was observed, 5 patients died of non
      disease-specific causes and active treatment was delivered in 20.5% of all
      patients. Triggers for active therapy were progression at biopsy (42%), rise in
      prostate-specific antigen level (27%), medical advice (16%) and patient's
      preference (10%), respectively. CONCLUSION: Our short-term results indicate that 
      in the hands of office-based urologists - active surveillance might represent a
      feasible treatment option for patients with localized PCa. The majority of
      patients were free of active treatment 2 years after AS initiation. Generally
      accepted inclusion and progression criteria are lacking and should be developed
      in order to facilitate and standardize AS in patients with low-risk PCa.

PMID- 25391441
TI  - [Robot-assisted laparoscopic pyeloplasty in adults: Excellent long-term results
      of primary pyeloplasty].
AB  - PURPOSE: With the development of the robot-assisted surgical technique, robot
      assisted pyeloplasty (RAP) has become established as an alternative to open and
      laparoscopic surgery. Currently there are only a few single-center studies with
      larger numbers of cases and long-term results. The aim of this study was to
      investigate perioperative and long-term postoperative success rates of Anderson
      Hynes robot-assisted pyeloplasty (RAP) at a single center. MATERIALS AND METHODS:
      We retrospectively reviewed our RAP experience of 61 patients performed by two
      surgeons between 2004 and 2013 regarding operating time, length of hospital stay,
      perioperative complication, and success. Overall success was measured in terms of
      necessary redo pyeloplasty. We also identified patients with temporary stent
      placement due to symptomatic hydronephrosis or with further obstruction in
      diuretic renography. RESULTS: Median age, operating time, and follow-up were 33
      years, 195 min, and 64 months, respectively. No conversion to open procedure was
      necessary. The success rate was 98% (n=60) with 1 patient undergoing open redo
      pyeloplasty due to a recurrent stenosis. Temporary stent placement was required
      in 3 patients due to pyelonephritis and dilatation. CONCLUSION: Satisfying long
      term success rates including low complication rates of RAP were obtained in this
      study. RAP presents a safe and standardized procedure for symptomatic
      ureteropelvic junction obstruction.

PMID- 25391442
TI  - [Use of botulinum toxin type A in non-neurogenic overactive bladder.
      Recommendations of the Working Group Urological Functional Diagnostics and
      Urology in Women].
AB  - The use of botulinum toxin for the treatment of neurogenic detrusor overactivity
      was first described in 2000 and thereafter botulinum toxin has also been used in
      non-neurogenic overactive bladder. In current guidelines intravesical injection
      of onabotulinumtoxin A in refractory patients is recommended. Our aim is to
      provide some clinically relevant recommendations from the Working Group
      Urologische Funktionsdiagnostik und Urologie der Frau for diagnostics and
      treatment with onabotulinumtoxin A of patients with non-neurogenic overactive
      bladder. 

PMID- 25391443
TI  - [Health care research - something new again?].

PMID- 25391444
TI  - Physical and biological assessments of the innovative bilayered wound dressing
      made of silk and gelatin for clinical applications.
AB  - The physical and biological assessments of the innovative bilayered wound
      dressing made of silk and gelatin that we have developed previously were
      performed to evaluate its efficacy for clinical applications. The absorption
      ability and dehydration rate of the dressing were assessed using the split
      thickness skin graft and leg ulcer wound bed models. The bioactivities of the
      bilayered wound dressing were evaluated. The bilayered dressing showed continuous
      absorption rate of wound exudate, providing the suitability for the wound with
      extended inflammation phase. The dehydration rate of the bilayered dressing was
      comparable to the commercially available dressing of which the moisture
      maintenance capability is claimed. The bilayered dressing showed good
      conformability, as can be seen by the homogeneous distribution pattern of
      bromophenol blue absorbed. In terms of biological activities, the bilayered
      dressing was less toxic to skin cells than the commercially available dressing.
      The bilayered dressing was also shown to promote cell migration and collagen
      production due to the bioactive protein components. We here concluded that the
      superior properties of the bilayered dressing over the commercially available
      dressing were the conformability and biological activities to accelerate the
      wound healing, while the other properties were comparable to those of
      commercially available dressing. The data obtained in this study would be very
      useful for the further evaluation of the bilayered dressing in clinical trial. 

PMID- 25391445
TI  - Composition-structure-property relationships for non-classical ionomer cements
      formulated with zinc-boron germanium-based glasses.
AB  - Non-classical ionomer glasses like those based on zinc-boron-germanium glasses
      are of special interest in a variety of medical applications owning to their
      unique combination of properties and potential therapeutic efficacy. These
      features may be of particular benefit with respect to the utilization of glass
      ionomer cements for minimally invasive dental applications such as the atruamatic
      restorative treatment, but also for expanded clinical applications in orthopedics
      and oral-maxillofacial surgery. A unique system of zinc-boron-germanium-based
      glasses (10 compositions in total) has been designed using a Design of Mixtures
      methodology. In the first instance, ionomer glasses were examined via
      differential thermal analysis, X-ray diffraction, and (11)B MAS NMR spectroscopy
      to establish fundamental composition - structure-property relationships for the
      unique system. Secondly, cements were synthesized based on each glass and
      handling characteristics (working time, Wt, and setting time, St) and compression
      strength were quantified to facilitate the development of both experimental and
      mathematical composition-structure-property relationships for the new ionomer
      cements. The novel glass ionomer cements were found to provide Wt, St, and
      compression strength in the range of 48-132 s, 206-602 s, and 16-36 MPa,
      respectively, depending on the ZnO/GeO2 mol fraction of the glass phase. A lower
      ZnO mol fraction in the glass phase provides higher glass transition temperature,
      higher N4 rate, and in combination with careful modulation of GeO2 mol fraction
      in the glass phase provides a unique approach to extending the Wt and St of glass
      ionomer cement without compromising (in fact enhancing) compression strength. The
      data presented in this work provide valuable information for the formulation of
      alternative glass ionomer cements for applications within and beyond the dental
      clinic, especially where conventional approaches to modulating working time and
      strength exhibit co-dependencies (i.e. the enhancement of one property comes at
      the expense of the other) and therefore limit development strategies. 

PMID- 25391446
TI  - Aroma compounds in Japanese sweet rice wine (Mirin) screened by aroma extract
      dilution analysis (AEDA).
AB  - Thirty-nine key aroma compounds were newly identified or tentatively identified
      in the aroma concentrate of Japanese sweet rice wine (Mirin) by an aroma extract
      dilution analysis technique based on the 68 detected peaks. Among them, 3
      (methylthio)propanal, 3-hydroxy-4,5-dimethyl-2(5H)-furanone, 3-methylbutanoic
      acid, 2-methylbutanoic acid, and 2-methoxy-4-vinylphenol were detected with the
      highest FD factors in this study. 

PMID- 25391448
TI  - Plant cell piercing by a predatory mite: evidence and implications.
AB  - Omnivorous arthropods can play an important role as beneficial natural enemies
      because they can sustain their populations on plants when prey is scarce, thereby
      providing prophylactic protection against an array of herbivores. Although some
      omnivorous mite species of the family Phytoseiidae consume plant cell-sap, the
      feeding mechanism and its influence on the plant are not known. Using scanning
      electron microscopy we demonstrated that the omnivorous predatory mite Euseius
      scutalis penetrates epidermal cells of pepper foliage and wax membranes.
      Penetration holes were teardrop shape to oval, of 2-5 um diameter. The
      similarities between penetration holes in pollen grains and in epidermal cells
      implied that the same penetration mechanism is used for pollen feeding and plant
      cell-sap uptake. Variation in shape and size of penetration holes in leaves and a
      wax membrane were attributed to different mite life stages, depth of penetration
      or the number of chelicerae puncturing (one or both). Punctured stomata,
      epidermal and vein cells appeared flat and lacking turgor. When the mite
      penetrated and damaged a single cell, neighboring cells were most often intact.
      In a growth chamber experiment very large numbers of E. scutalis negatively
      affected the growth of young pepper plants. Consequently caution should be taken
      when applying cell-piercing predators to young plants. Further studies are needed
      to take advantage of the potential sustainability of plant cell-sap feeding
      predators.

PMID- 25391447
TI  - Humanin attenuates Alzheimer-like cognitive deficits and pathological changes
      induced by amyloid beta-peptide in rats.
AB  - Amyloid beta-peptide (Abeta) has been implicated as a key molecule in the
      neurodegenerative cascades of Alzheimer's disease (AD). Humanin (HN) is a
      secretory peptide that inhibits the neurotoxicity of Abeta. However, the
      mechanism(s) by which HN exerts its neuroprotection against Abeta-induced AD-like
      pathological changes and memory deficits are yet to be completely defined. In the
      present study, we provided evidence that treatment of rats with HN increases the
      number of dendritic branches and the density of dendritic spines, and upregulates
      pre- and post-synaptic protein levels; these effects lead to enhanced long-term
      potentiation and amelioration of the memory deficits induced by Abeta(1-42). HN
      also attenuated Abeta(1-42)-induced tau hyperphosphorylation, apparently by
      inhibiting the phosphorylation of Tyr307 on the inhibitory protein phosphatase-2A
      (PP2A) catalytic subunit and thereby activating PP2A. HN also inhibited apoptosis
      and reduced the oxidative stress induced by Abeta(1-42). These findings provide
      novel mechanisms of action for the ability of HN to protect against Abeta(1-42)
      induced AD-like pathological changes and memory deficits.

PMID- 25391449
TI  - Palladium nanoparticles decorated on reduced graphene oxide rotating disk
      electrodes toward ultrasensitive hydrazine detection: effects of particle size
      and hydrodynamic diffusion.
AB  - Although metal nanoparticle/graphene composites have been widely used as the
      electrode in electrochemical sensors, two effects, consisting of the particle
      size of the nanoparticles and the hydrodynamic diffusion of analytes to the
      electrodes, are not yet fully understood. In this work, palladium
      nanoparticles/reduced graphene oxide (PdNPs/rGO) composites were synthesized
      using an in situ polyol method. Palladium(II) ions and graphene oxide were
      reduced together with a reducing agent, ethylene glycol. By varying the
      concentration of palladium(II) nitrate, PdNPs with different sizes were decorated
      on the surface of rGO sheets. The as-fabricated PdNPs/rGO rotating disk
      electrodes (RDEs) were investigated toward hydrazine detection. Overall, a 3.7 +/
      1.4 nm diameter PdNPs/rGO RDE exhibits high performance with a rather low limit
      of detection of about 7 nM at a rotation speed of 6000 rpm and provides a wide
      linear range of 0.1-1000 MUM with R(2) = 0.995 at 2000 rpm. This electrode is
      highly selective to hydrazine without interference from uric acid, glucose,
      ammonia, caffeine, methylamine, ethylenediamine, hydroxylamine, n-butylamine,
      adenosine, cytosine, guanine, thymine, and l-arginine. The PdNPs/rGO RDEs with
      larger sizes show lower detection performance. Interestingly, the detection
      performance of the electrodes is sensitive to the hydrodynamic diffusion of
      hydrazine. The as-fabricated electrode can detect trace hydrazine in wastewater
      with high stability, demonstrating its practical use as an electrochemical
      sensor. These findings may lead to an awareness of the effect of the hydrodynamic
      diffusion of analyte that has been previously ignored, and the 3.7 +/- 1.4 nm
      PdNPs/rGO RDE may be useful toward trace hydrazine detection, especially in
      wastewater from related chemical industries. 

PMID- 25391451
TI  - Severe congenital neutropenia due to G6PC3 deficiency: early and delayed
      phenotype in two patients with two novel mutations.
AB  - Severe Congenital Neutropenia type 4 (SCN4, OMIM 612541) is a rare autosomal
      recessive disease due to mutations in the G6PC3 gene. The phenotype comprises
      neutropenia of variable severity and other anomalies including congenital heart
      defects, prominent superficial veins, uro-genital anomalies, facial dysmorphism,
      growth and developmental delay and intermittent thrombocytopenia. In some
      patients, SCN represents the only manifestation of the disease. Variable findings
      have been reported at bone marrow examination ranging from a maturation arrest at
      the myelocyte/promyelocyte stage (either in a hypocellular or hypercellular
      context) to myelokathexis. Here we report two patients harbouring two novel
      mutations in the G6PC3 gene, including the first Italian patient even described.
      Both the patients share profound neutropenia with severe infections early in
      life; in one case non-hematopoietic stigmata of the syndrome, including evident
      facial dysmorphism and vascular anomalies, appeared gradually over time,
      prominently in the second decade. Therefore, G6PC3 defects should be considered
      in any case of congenital, unexplained neutropenia regardless of the clinical
      phenotype. Both patients are on G-CSF treatment with no evidence of malignant
      evolution. Even if G6PC3 deficiency seems not to have a propensity towards
      malignancy, a careful evaluation is warranted. 

PMID- 25391450
TI  - Social support mediates the association of health literacy and depression among
      racially/ethnically diverse smokers with low socioeconomic status.
AB  - Nearly half of U.S. adults have health literacy (HL) difficulties, and lack the
      ability to effectively obtain, process, and understand health information. Poor
      HL is associated with depression, yet mechanisms of this relation are unclear.
      This study examined whether social support mediated the relation between HL and
      depressive symptoms in 200 low-socioeconomic status (SES), racially/ethnically
      diverse smokers enrolled in cessation treatment. Mediation analyses were
      conducted using bootstrapping and controlling for SES and nicotine dependence. In
      simple mediation models, social support [Interpersonal Support Evaluation List
      (ISEL) total, subscales (Appraisal, Belonging, Tangible)] mediated the effect of
      HL on depression, such that lower HL was associated with lower perceived support,
      which predicted higher depressive symptoms (ps < .05). A multiple mediation
      model, with ISEL subscales entered simultaneously as mediators, was significant
      (p < .05) but only the Belonging subscale demonstrating independent significance
      (p < .05). Thus, social support may be a critical factor underlying the HL
      depression relationship in low-SES, racially/ethnically diverse smokers. 

PMID- 25391452
TI  - Pseudogene in cancer: real functions and promising signature.
AB  - Pseudogenes were initially regarded as non-functional genomic fossils resulted
      from inactivating gene mutations during evolution. However, later studies
      revealed that they play a plethora of roles at multiple levels (DNA, RNA and/or
      protein) in diverse physiological and pathological processes, especially in
      cancer, both parental-gene-dependently and parental-gene-independently.
      Pseudogenes can interact with parental genes or other gene loci, leading to
      alteration in their sequences and/or transcriptional activities. Pseudogene
      derived RNAs play multifaceted roles in post-transcriptional regulation as
      antisense RNAs, endogenous small-interference RNAs, competing endogenous RNAs and
      so on. Pseudogenic proteins can mirror, mimic or interfere with the functions of
      their parental counterparts. Herein, we discuss the general aspects (origination,
      classification, identification) of pseudogenes, focus on their multiple functions
      in cancer pathogenesis and prospect the potentials they hold as molecular
      signatures assisting in cancer reclassification and tailored therapy. 

PMID- 25391453
TI  - Next-generation sequencing of nine atrial fibrillation candidate genes identified
      novel de novo mutations in patients with extreme trait of atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac
      arrhythmia. Genome-wide association studies (GWAS) have identified common
      variants in nine genomic regions associated with AF (KCNN3, PRRX1, PITX2, WNT8A,
      CAV1, C9orf3, SYNE2, HCN4 and ZFHX3 genes); however, the genetic variability of
      these risk variants does not explain the entire genetic susceptibility to AF.
      Rare variants missed by GWAS may also contribute to genetic risk of AF. METHODS:
      We used an extreme trait design to sequence carefully selected probands with
      extreme phenotypes and their unaffected parents to identify rare de novo variants
      or mutations. Based on the hypothesis that common and rare variants may colocate
      in the same disease susceptibility gene, we used next-generation sequencing to
      sequence these nine published AF susceptibility genes identified by GWAS (a total
      of 179 exons) in 20 trios, 200 unrelated patients with AF and 200 non-AF
      controls. RESULTS: We identified a novel mutation in the 5' untranslated region
      of the PITX2 gene, which localised in the transcriptionally active enhancer
      region. We also identified one missense exon mutation in KCNN3, two in ZFHX3 and
      one in SYNE2. None of these mutations were present in other unrelated patients
      with AF, healthy controls, unaffected parents and are thus novel and de novo
      (p<10(-4)). Functional study showed that the mutation in the 5' untranslated
      region of the PITX2 gene significantly downregulated PITX2 expression in atrial
      myocytes, either in basal condition or during rapid pacing. In silico analysis
      showed that the missense mutation in ZFHX3 results in damage of the ZFHX3 protein
      structure. CONCLUSIONS: The genetic architecture of subjects with extreme
      phenotypes of AF is similar to that of rare or Mendelian diseases, and mutations
      may be the underlying cause.

PMID- 25391455
TI  - Customized patterned substrates for highly versatile correlative light-scanning
      electron microscopy.
AB  - Correlative light electron microscopy (CLEM) combines the advantages of light and
      electron microscopy, thus making it possible to follow dynamic events in living
      cells at nanometre resolution. Various CLEM approaches and devices have been
      developed, each of which has its own advantages and technical challenges. We here
      describe our customized patterned glass substrates, which improve the feasibility
      of correlative fluorescence/confocal and scanning electron microscopy. 

PMID- 25391454
TI  - Dendrofalconerol A sensitizes anoikis and inhibits migration in lung cancer
      cells.
AB  - Resistance to anoikis, enhanced cell motility, and growth in anchorage
      independent conditions are hallmarks of highly metastatic cancer cells. The
      present study demonstrates the anoikis-sensitizing and anti-migration activities
      of dendrofalconerol A (DF-A), a pure bis(bibenzyl) isolated from the stem of
      Dendrobium falconeri (Orchidaceae), and its underlying mechanisms in human lung
      cancer H460 cells. DF-A at non-toxic concentrations significantly increased the
      anoikis response of the cancer cells, but caused no toxic effect on normal
      keratinocytes. In addition, DF-A significantly inhibited the growth of lung
      cancer cells in anchorage-independent conditions. Western blot analysis revealed
      that the anoikis-sensitizing effect of such a compound involves its ability to
      suppress survival signals as well as anti-apoptotic proteins, namely, activated
      protein kinase B (Akt) and Bcl-2. Furthermore, DF-A decreased caveolin-1 (Cav-1),
      a protein responsible for aggressiveness, while having no effect on Bax, Mcl-1,
      and activated Erk (p42/44) proteins. In the case of cell motility, DF-A exhibited
      strong anti-migration activity with the mechanism involving suppression of pFAK
      and Rho-GTP, but had no effect on Rac-GTP in lung cancer cells. Taken together,
      DF-A possesses anoikis-sensitizing activity along with anti-migration effects,
      and may be developed as a novel active compound for cancer treatment. 

PMID- 25391456
TI  - CRY1, CRY2 and PRKCDBP genetic variants in metabolic syndrome.
AB  - The circadian clock affects metabolic cycles, and there is a link between
      circadian clock genes and metabolic syndrome. Therefore, we wanted to investigate
      whether variants of the core circadian clock genes, cryptochrome circadian clocks
      1 and 2 (CRY1 and CRY2), or those of protein kinase C, delta binding protein
      (PRKCDBP), which regulate the interactions and abundance of dimers of the period
      and cryptochrome proteins, are associated with metabolic syndrome or its
      components. The association of 48 single-nucleotide polymorphisms (SNPs) from
      CRY1, CRY2 and PRKCDBP genes with metabolic disorder or its components was
      analyzed in a sample of 5910 individuals. Genotyping was performed using the
      Sequenom MassARRAY system. SNPs and haplotypes were analyzed using linear or
      logistic regression with additive models controlling for age and sex. Continuous
      phenotypes were permuted 10,000 times. False discovery rate q-values were
      calculated to correct for multiple testing. Overall, CRY1 and CRY2 variants
      showed nominal association with the metabolic syndrome components, hypertension
      and triglyceride levels, and one CRY2 variant had an association with metabolic
      syndrome, although none of these associations yielded significant q-values.
      However, the haplotype analysis of these variants supported the association of
      CRY1 with arterial hypertension and elevated blood pressure. Further studies are
      warranted regarding the role of CRY1 in cardiovascular diseases.

PMID- 25391457
TI  - Higher circulatory level of endothelin-1 in hypertensive subjects screened
      through a cross-sectional study of rural Bangladeshi women.
AB  - Endothelin-1 (ET-1) is a potential marker of the endothelial dysfunction, which
      has been shown to be elevated in hypertensive subjects. No previous study has
      investigated the circulatory level of ET-1 and hypertension in a South Asian
      country. The present study assessed the circulating levels of ET-1 in subjects
      with or without hypertension and further examined the association of ET-1 with
      clinical and metabolic parameters. A total of 2543 rural Bangladeshi women with a
      mean age of 44.5 years were studied using a cross-sectional survey. Multiple
      regressions were used to examine the association between the circulatory ET-1
      levels and hypertension. The prevalence of hypertension was 29.3%. The ET-1
      levels were significantly higher in the hypertensive (mean 3.08 pg ml(-1), s.e.
      (0.19)) than in the non-hypertensive subjects (mean 2.01 pg ml(-1), s.e. (0.03))
      (P = 0.001). After adjusting for age, the ET-1 level had significant positive
      associations with the diastolic blood pressure (P = 0.002), systolic blood
      pressure (P = 0.001), mean arterial pressure (P = 0.002) and fasting blood
      glucose (P = 0.002). In a tertile analysis, we found that hypertension in the
      subjects was significantly increased as the levels of ET-1 increased (P for the
      trend = 0.001). In a stepwise multiple regression analysis, after adjusting for
      age and all other potential variables, we found that the mean arterial pressure
      and the fasting plasma levels have significant associations with the ET-1 level.
      The present study demonstrates that there is a higher concentration of ET-1 among
      the hypertensive subjects in an apparently healthy population of Bangladeshi
      rural women. The relationship between ET-1 and hypertension requires further
      investigation to define the clinical utility and predictive value of serum ET-1
      levels for hypertension for a South Asian population.

PMID- 25391458
TI  - Development of a risk prediction model for incident hypertension in a working-age
      Japanese male population.
AB  - The aim of this study was to develop a risk prediction model for incident
      hypertension in a Japanese male population. Study participants included 15,025
      nonhypertensive Japanese male workers (mean age, 38.8+/-8.9 years) who underwent
      an annual medical checkup at a company. The participants were followed-up for a
      median of 4.0 years to determine new-onset hypertension, defined as a systolic
      blood pressure (BP) ?140 mm Hg, a diastolic BP ?90 mm Hg, or the initiation of
      antihypertensive medication. Participants were divided into the following two
      cohorts for subsequent analyses: the derivation cohort (n=12,020, 80% of the
      study population) and the validation cohort (n=3005, the remaining 20% of the
      study population). In the derivation cohort, a multivariate Cox proportional
      hazards model demonstrated that age, body mass index, systolic and diastolic BP,
      current smoking status, excessive alcohol intake and parental history of
      hypertension were independent predictors of incident hypertension. Using these
      variables, a risk prediction model was constructed to estimate the 4-year risk of
      incident hypertension. In the validation cohort, the risk prediction model
      demonstrated high discrimination ability and acceptable calibration, with a C
      statistic of 0.861 (95% confidence interval 0.844, 0.877) and a modified Hosmer
      Lemeshow chi2 statistic of 15.2 (P=0.085). A risk score sheet was constructed to
      enable the simple calculation of the approximate 4-year probability of incident
      hypertension. In conclusion, a practical risk prediction model for incident
      hypertension was successfully developed in a working-age Japanese male
      population.

PMID- 25391459
TI  - DNA profiles from fingernails using direct PCR.
AB  - We report on the successful routine amplification of DNA profiles from small
      sections of fingernails using direct PCR. The data are from 40 nail clippings
      from eight donors where approximately 4 mm(2) of nail is added directly to the
      PCR. The NGMTM kit was used that amplifies 15 STR loci plus amelogenin. No
      increase in cycle number was used and no enrichment of the PCR products was
      performed. Full DNA profiles were observed in 17 of the 40 profiles with 21
      generating partial DNA profiles. The process omits the DNA extraction process,
      and hence there is no opportunity to quantify the DNA prior to amplifying the
      STRs, but by not performing a DNA extraction step, the amount of DNA available
      for PCR is maximized. Single source DNA profiles were observed in 29 of the 38
      profiles obtained. The source of the DNA is assumed to be adhering to the
      underside of the nail. This simple method offers a significant reduction in time
      to generate DNA profiles from nail clippings, such as those taken from victims of
      mass disasters, and should be included into a forensic process relatively easily
      as it requires no change to manufacturer's instructions for amplification.

PMID- 25391460
TI  - Increased systolic blood pressure reactivity to acute stress is related with
      better self-reported health.
AB  - The stress reactivity hypothesis posits that the magnitude of cardiovascular
      reactions to acute stress tasks is related with future blood pressure status,
      heart hypertrophy, and atherosclerosis. We assessed the stress reactivity
      hypothesis and aimed to identify which physiological indices (blood pressure,
      heart-rate, cortisol, salivary immunoglobulin A (sIgA)) related to self-reported
      mental and physical health. We also assessed if physiological reactions elicited
      by an acute stressor were more related than basal assessments. Participants
      provided physiological samples, self-reported stress and health-data before and
      after an assessed 5-7 minute academic oral presentation. In hierarchical
      regression models, increased systolic and reduced sIgA reactivity was associated
      with better perceptions of mental health. Reactivity data were more related to
      self-reported data than basal data. In line with the only 2 studies to assess the
      reactivity hypothesis with self-perceived health, increased systolic reactivity
      was best associated with better perceived physical and mental health. The
      findings suggest that increased SBP reactivity may also be associated with
      positive health outcomes. Further research is required to determine if increased
      or decreased sIgA reactivity is most predictive of future morbidity. 

PMID- 25391461
TI  - Potentially toxic elements (PTEs) in soils from the surroundings of the Trans
      Amazonian Highway, Brazil.
AB  - The Trans-Amazonian Highway (TAH) is located in the northern region of Brazil,
      comprising a border region where agricultural, mining, and logging activities are
      the main activities responsible for fostering economic development, in addition
      to large hydroelectric plants. Such activities lead to environmental
      contamination by potentially toxic elements (PTEs). Environmental monitoring is
      only possible through the determination of element contents under natural
      conditions. Many extraction methods have been proposed to determine PTEs'
      bioavailability in the soil; however, there is no consensus about which extractor
      is most suitable. In this study, we determined the contents of PTEs in soils in
      the surroundings of TAH after mineral extraction with
      diethylenetriaminepentaacetic acid-triethanolamine (DTPA-TEA), Mehlich I, and
      Mehlich III solutions. Soil samples were collected in areas of natural vegetation
      in the vicinity of TAH in the state of Para, Brazil. Chemical attributes and
      particle size were determined, besides concentrations of Fe, Al, Mn, and Ti by
      sulfuric acid digestion, Si after alkaline solution attack, and poorly
      crystalline Fe, Al, and "free" Fe oxides. Mehlich III solution extracted greater
      contents from Fe, Al, and Pb as compared to Mehlich I and DTPA-TEA and similar
      contents from Cd, Mn, Zn, and Cu. Significant correlations were found between
      concentrations of PTEs and the contents of Fe and Mn oxides as well as organic
      carbon and soil cation exchange capacity. Contents of Cu, Mn, Fe, and Zn by the
      three methods were positively correlated. 

PMID- 25391462
TI  - Trade-off between water pollution prevention, agriculture profit, and farmer
      practice--an optimization methodology for discussion on land-use adjustment in
      China.
AB  - Agricultural decision-making to control nonpoint source (NPS) water pollution may
      not be efficiently implemented, if there is no appropriate cost-benefit analysis
      on agricultural management practices. This paper presents an interval-fuzzy
      linear programming (IFLP) model to deal with the trade-off between agricultural
      revenue, NPS pollution control, and alternative practices through land adjustment
      for Wuchuan catchment, a typical agricultural area in Jiulong River watershed,
      Fujian Province of China. From the results, the lower combination of practice 1,
      practice 2, practice 3, and practice 7 with the land area of 12.6, 5.2, 145.2,
      and 85.3 hm(2), respectively, could reduce NPS pollution load by 10%. The
      combination yields an income of 98,580 Chinese Yuan/a. If the pollution reduction
      is 15%, the higher combination need practice 1, practice 2, practice 3, practice
      5, and practice 7 with the land area of 54.4, 23.6, 18.0, 6.3, and 85.3 hm(2),
      respectively. The income of this combination is 915,170 Chinese Yuan/a. The
      sensitivity analysis of IFLP indicates that the cost-effective practices are
      ranked as follows: practice 7 > practice 2 > practice 1 > practice 5 > practice 3
      > practice 6 > practice 4. In addition, the uncertainties in the agriculture NPS
      pollution control system could be effectively quantified by the IFLP model.
      Furthermore, to accomplish a reasonable and applicable project of land-use
      adjustment, decision-makers could also integrate above solutions with their own
      experience and other information.

PMID- 25391463
TI  - [Clinical characteristics of biliary tract infection and acalculous cholecystitis
      after cardiovascular surgery].
AB  - Biliary tract infection (BTI) including acalculous cholecystitis is a rare but
      life-threatening complication after cardiovascular surgery. The objective of our
      study was to describe epidemiology, clinical characteristics, and risk factors of
      BTI after cardiovascular surgery. From January 2007 to December 2011, 586
      consecutive patients(age68+/-11;397 men,189 women)were enrolled in this study.
      BTI was diagnosed according to Centers for Disease Control and Prevention (CDC)
      surveillance criteria for healthcare associated infection. Data collection
      included preoperative, intraoperative, and post-operative variables. The overall
      incidence of BTI was 3.9%. The mortality in BTI group was significantly higher
      than that in non-BTI group (17.1% vs 5.5%, p<0.05). Multi-logistic analysis
      revealed that operation of the thoracic aorta( p<0.05) and massive
      transfusion(p<0.01) were independent risk factors for BTI after cardiovascular
      surgery.

PMID- 25391464
TI  - [Student education with using training simulator for endoscopic surgery].
AB  - Video-assisted thoracic surgery (VATS) has become popular in the field of chest
      surgery. Recently, there has been a gradual reduction in the number of surgeons
      in Japan, which thus increases concerns regarding a potential shortage in the
      number of surgeons in the future. In this study, we evaluated the efficacy of
      using a surgical simulator with an endoscopic simulator to provide practical
      training for 245 medical students. Three different tests were performed with a
      one-week interval between each test, and the task completion time between the 1st
      and 2nd training sessions was then analyzed. A reduction in the time required to
      perform the tasks was observed. In addition, 95% of the subjects had a positive
      opinion regarding the application of the device for practical training, while 85%
      reported an increased interest in surgery. No significant relationships were
      observed between the task completion time and the degree of proficiency in
      performing the task or between the results of students choosing to become
      surgeons and those not choosing to become surgeons in the future according to a
      follow-up study. The students who later decided to become surgeons tended to
      express a positive opinion on the questionnaire compared with the non
      departmental staff. As a result, providing student education using a training
      simulator for endoscopic surgery is therefore considered to have a beneficial
      effect in increasing the number of medical school students who later decide to
      become surgeons. 

PMID- 25391465
TI  - [Successful endovascular repair of a ruptured thoracoabdominal aortic aneurysm
      with severe mural thrombus].
AB  - A 51-year-old man was transferred to our hospital on an emergency basis
      complaining of a sudden onset of severe left lumbar back pain. An emergency
      contrasted computed tomography showed a ruptured thoracoabdominal aortic
      aneurysm( rTAAA:Crawford classification type III). The ruptured site was near the
      aortic bifurcation, and the aneurysm had a relatively narrow segment with an
      extensive mural thrombus just below the renal arteries. Considering the high
      mortality of open surgery for the rTAAA and the poor general condition of the
      patient, we decided to perform endovascular aneurysm repair (EVAR) as a rescue
      procedure using the narrowed segment by the thrombus for a proximal landing zone.
      The abdominal part of the thoracoabdominal aortic aneurysm (TAAA) was
      successfully excluded with a stent graft to obtain complete hemostasis. The
      postoperative course was uneventful except for the need for hemodialysis. Even
      though there is a risk of developing late type 1 endoleak, this procedure can be
      a feasible option as a rescue procedure or a bridge to radical open surgery for
      ruptured TAAA in a specially anatomical setting like this case. 

PMID- 25391466
TI  - [Tension hemothorax accompanying rupture of the descending aortic aneurysm].
AB  - Although, tension hemothorax appears along with thoracic injuries in many cases,
      the incidence is rare and the concept itself has not yet been established.
      Moreover, reports on tension hemothorax caused by the rupture of thoracic aortic
      aneurysms are very rare. Herein, we report a case in which thoracic endovascular
      aortic repair( TEVAR) was carried out following chest drainage in order to treat
      tension hemothorax accompanying rupture of the descending aortic aneurysm, thus
      leading to the survival of the patient. 

PMID- 25391467
TI  - [Anomalous systemic arterial supply to left basal lung with anomalous return of
      V6].
AB  - The patient was 52-year-old woman. Her chief compliant was bloody sputum. The
      computed tomography revealed an anomalous artery from descending aorta running
      into left lung basal segment and anomalous left V6 return to superior pulmonary
      vein. The bronchoscopic examination showed normal bronchial branches. Under the
      diagnosis of anomalous systemic arterial supply to left basal lung without
      sequestration, left lower lobectomy was performed. Microscopically, the pulmonary
      artery showed intimal thickening and alveolar collapse with interstitial fibrosis
      were seen. The postoperative course was uneventful and she discharged at 6th
      postoperative day. 

PMID- 25391468
TI  - [Surgical technique of saphenous vein harvesting using a Cusco vaginal speculum].
AB  - We used Cusco vaginal speculum in harvesting saphenous vein graft (SVG) as an
      assist device for making a skin tunnel. After making 2 incisions of 3 to 4 cm,
      the SVG was dissected in a usual procedure. Then Cusco vaginal speculum was
      inserted into the skin tunnel between the 2 incisions. The SVG was dissected in a
      usual fashion under direct vision with the speculum. This procedure requires only
      small incisions, short learning curve and low cost. The new technique using Cusco
      vaginal speculum can be a reliable option for harvesting SVG. 

PMID- 25391469
TI  - [Second use of preserved aortic cusps for bentall procedure after aortic valve
      replacement with intravalvular implantation technique in aortitis syndrome].
AB  - A 44-year-old woman who had undergone aortic valve replacement with intravalvular
      implantation technique due to aortitis syndrome 13 years before, required Bentall
      procedure and hemiarch replacement because of the tissue valve dysfunction and
      the root and ascending aortic aneurysms. The exposed native aortic cusps
      sandwiched between the felt pledgets and the tissue valve seemed to be useful in
      reinforcing the proximal anastomosis of the composite graft. A combination of an
      intravalvular implantation technique and a skirted composite graft technique was
      applied, and her postoperative course has been uneventful for more than 2 and a
      half years. 

PMID- 25391470
TI  - [Three cases of cardiac tumor; an approach to excise a large tumor in the left
      atrium].
AB  - Tumors originated from the heart are very rare disease and their
      clinicopathological state has not been fully recognized. Cardiac tumors are most
      frequently found in the left atrium. An initial treatment is a surgical excision
      of tumors entirely including their pedicles. And regardless of benign or
      malignant tumors, it is most important to remove them completely. However, a
      complete resection of cardiac tumors in the left atrium becomes more difficult in
      cases of larger sizes or wide expanding of the pedicles. In such cases, we
      recommend to choose a right-sided approach to the left atrium, so that it enables
      to be easier to examine all areas of the left atrium for a complete resection of
      cardiac tumors. We have excised successfully in three cases of larger cardiac
      tumors originated from the left atrium employing a right-sided left atriotomy. 

PMID- 25391471
TI  - [Incidental diagnosis of giant cell arteritis during a hybrid surgical approach
      in a patient with annuloaortic ectasia and an extensive thoracic aortic
      aneurysm].
AB  - We report a case of giant cell arteritis that was incidentally diagnosed during a
      hybrid( open surgical and endovascular) approach to an extensive thoracic aortic
      disease. A 78-year-old man was admitted for the evaluation and treatment of
      annuloaortic ectasia and an extensive thoracic aortic aneurysm. We performed
      aortic root replacement (Bentall procedure) and total aortic arch replacement
      using the elephant trunk technique under hypothermic circulatory arrest.
      Pathological examination of the aneurysmal wall revealed giant cell arteritis. He
      had no specific symptoms such as headache, jaw claudication, or vision loss.
      Because no findings except for a slightly elevated erythrocyte sediment rate were
      suggestive of active vasculitis, he was discharged from hospital without steroid
      therapy 6 weeks after open surgery. However, 4 weeks later he returned in
      hemorrhagic shock due to rupture of a residual descending thoracic aortic
      aneurysm. He underwent emergency endovascular repair but died intraoperatively.
      In conclusion, early second-stage procedure and postoperative steroid therapy may
      be useful in a patient with aortic aneurysm in giant cell arteritis undergoing a
      hybrid procedure. 

PMID- 25391472
TI  - [Interlobar neurinoma with a cystic formation derived from the vagal pulmonary
      branches].
AB  - A 60-year-old woman was referred to our hospital because of an abnormal shadow in
      the chest roentgenogram. Chest computed tomography (CT) showed the mass with
      heterogeneous low attenuation in the right lower lobe (S6), 40 mm in size.
      Fluorodeoxyglucose-positron emission tomography (FDGPET)/CT scanning revealed
      slight positive reaction in the right lower lobe lesion. The video-assisted
      thoracoscopic surgery (VATS) was performed to establish diagnosis and treat.
      Intraoperative finding showed the tumor was located between the left upper lobe
      and the left lower lobe, and the inflow of the vagal pulmonary branches.
      Histopathological examination showed no malignancy and neurinoma with a cystic
      formation derived from the vagus nerve. 

PMID- 25391473
TI  - [Pulmonary metastasis of sarcomatous component of adrenocortical carcinoma].
AB  - A 43-year-old man presented with a pulmonary nodule in the left lower lobe and he
      consulted our hospital one year after resection of left adrenocortical carcinoma.
      We performed a wedge resection of the left lower pulmonary lobe for diagnosis.
      The tumor was diagnosed as a metastatic sarcoma, but the primary site could not
      be resolved. We assessed the histopathology of the adrenal tumor, which was
      obtained from the patient's former hospital, and it showed that the tumor
      consisted of both carcinomatous and sarcomatous components. This enabled us to
      diagnose the nodule as a pulmonary metastasis from the adrenocortical carcinoma.
      Adrenocortical carcinoma with a sarcomatous component is very rare. This case is
      a first report of a resected pulmonary metastasis of sarcomatous component of
      adrenocortical carcinoma. 

PMID- 25391474
TI  - [Stuck valve detected during aortic valve replacement; report of a case].
AB  - Aortic valve replacement, ascending aorta replacement and coronary artery bypass
      grafting were performed in a 61-year-old woman with aortic stenosis, ascending
      aortic aneurysm, and angina pectoris. However, immediately after surgery,
      transient hypotension and pulmonary hypertension repeated every few
      beats.Transesophageal echocardiography revealed a stuck valve, and reimplantation
      was carried out. The patient's postoperative course was uneventful. We present a
      case of successful treatment of valve dysfunction immediately after valve
      replacement. 

PMID- 25391475
TI  - [Aortic root and arch replacement late after ascending aortic replacement for
      acute aortic dissection; report of a case].
AB  - Surgical treatment for acute type A aortic dissection remains controversial,
      especially when the aortic dissection extends to the aortic root and arch. A 73
      year-old woman presented with palpitation. She had previously undergone ascending
      aorta replacement for acute type A aortic dissection with reinforcement of the
      proximal and distal aortic stumps using gelatin-resorcinol-formaldehyde (GRF)
      glue, conducted by a different surgical team 7 years ago. Echocardiography and
      computed tomography revealed dilatation of both ends of the reconstructed aorta,
      with aortic valve insufficiency. Hence, we performed Bentall procedure, partial
      aortic arch replacement, and coronary artery bypass grafting. The postsurgical
      course was uneventful. Redo operations may be avoidable, if, in the initial
      operation for acute type A aortic dissection with dissected aortic root and arch,
      surgery is performed without use of GRF glue for reinforcement of stumps. We
      recommend to perform the Bentall procedure, partial remodeling procedure, or
      valve-sparing aortic root replacement for reconstruction of the aortic root and
      arch replacement for repair of the aortic arch. 

PMID- 25391476
TI  - [Giant aortic arch aneurysm following ligation of patent ductus arteriosus in an
      adult patient with Down syndrome; report of a case].
AB  - A 45-year-old male with Down syndrome( DS) had abnormal findings pointed out by
      chest X-ray and admitted to our hospital. He had undergone ligation of the patent
      ductus arteriosus 33 years before. Computed tomography showed a giant aortic
      aneurysm at the aortopulmonary window. Aortic arch replacement was performed
      under cardiopulmonary bypass and circulatory arrest. The postoperative course was
      uneventful. Postoperative ductal aneurysm in an adult is relatively rare and
      needs early operation because of the high risk of rupture. In this case,
      considering the size of the aneurysm, the timing of diagnosis seemed to be late.
      As the life expectancy of patients with DS has been lengthning recently, their
      regular health examinations is mandatory to improve the life expectancy and
      quality of life. 

PMID- 25391477
TI  - [Patent venous graft for the left anterior descending branch 25 years after
      surgery; report of a case].
AB  - We report a case of a patent venous graft for the left anterior descending branch
      25 years after surgery. In 1986 at the age of 59 years, the patient underwent
      coronary artery bypass grafting( CABG) to the left anterior descending(LAD)artery
      using a saphenous vein graft (SVG). In 2011, twenty-five years after the surgery,
      the patient experienced a chest pain and was hospitalized. Due to a strong chest
      pain and pulmonary edema, emergency coronary angiography was performed under
      tracheal intubation. The SVG was patent, but severe stenosis was found proximal
      to the middle of the graft. Although percutaneous coronary intervention with a
      bare-metal stent was performed, the patient died of ventricular fibrillation on
      the 38th postoperative day. The use of arterial grafts for CABG is currently
      predominant, but SVG should still be considered a reliable alternative. 

PMID- 25391478
TI  - [Pulmonary lymphoepithelioma-like carcinoma; report of a case].
AB  - A 66-year-old male was referred to our hospital due to an abnormal chest shadow
      in the left lung detected on a medical examination. Chest computed tomography(CT)
      revealed a round mass of 40 mm in diameter in the left S10. Positron emission
      tomography (PET) scan showed fluorodeoxy glucose (FDG) accumulation and surgical
      biopsy was done. The intraoperative frozen histopathological diagnosis was
      mucosal associated lymphoid tissue( MALT) lymphoma or pseudoinflammatory tumor.
      By postoperative pathology, the mass was finally diagnosis as lymphoepithelioma
      like carcinoma (LELC) of the lung, pT2aN0M0 stage I B.After a month, left lower
      lobectomy with mediastinal lymph node dissection was performed. The association
      with Epstein-Barr virus was not demonstrated by EBER in situ hybridization. The
      patient was well without relapse at 24 months after surgery. 

PMID- 25391479
TI  - [Tracheal repair injury during thoracoscopic surgery for esophageal cancer after
      induction chemotherapy; report of a case].
AB  - 72-year-old female had thoracoscopic esophagectomy for advanced thoracic
      esophageal cancer after induction chemotherapy with CDDP(70 mg/m2, day 1) +5-FU
      (650 mg/m2, day 1-5). Since the membranous portion of trachea was injured due to
      dense adhesion thoracoscopic surgery was converted to mini-thoracotomy. Injured
      portion was closed with 4-0 absorbable suture, and covered with gastric tube for
      reconstruction through posterior mediastinal route. No respiratory complications
      occurred after surgery and the patient discharged at the 12 post operative days.

PMID- 25391480
TI  - Catastrophic childhood epilepsy: a recent convergence of basic and clinical
      neuroscience.
AB  - Advances in understanding the genetics and underlying pathology of the
      catastrophic childhood epilepsies are pointing toward treatments. 

PMID- 25391481
TI  - A multifunctional bispecific antibody protects against Pseudomonas aeruginosa.
AB  - Widespread drug resistance due to empiric use of broad-spectrum antibiotics has
      stimulated development of bacteria-specific strategies for prophylaxis and
      therapy based on modern monoclonal antibody (mAb) technologies. However, single
      mechanism mAb approaches have not provided adequate protective activity in the
      clinic. We constructed multifunctional bispecific antibodies, each conferring
      three mechanisms of action against the bacterial pathogen Pseudomonas aeruginosa
      by targeting the serotype-independent type III secretion system (injectisome)
      virulence factor PcrV and persistence factor Psl exopolysaccharide. A new
      bispecific antibody platform, BiS4, exhibited superior synergistic protection
      against P. aeruginosa-induced murine pneumonia compared to parent mAb
      combinations or other available bispecific antibody structures. BiS4alphaPa was
      protective in several mouse infection models against disparate P. aeruginosa
      strains and unexpectedly further synergized with multiple antibiotic classes even
      against drug-resistant clinical isolates. In addition to resulting in a
      multimechanistic clinical candidate (MEDI3902) for the prevention or treatment of
      P. aeruginosa infections, these antibody studies suggest that multifunctional
      antibody approaches may be a promising platform for targeting other antibiotic
      resistant bacterial pathogens. 

PMID- 25391482
TI  - Prediction of resistance development against drug combinations by collateral
      responses to component drugs.
AB  - Resistance arises quickly during chemotherapeutic selection and is particularly
      problematic during long-term treatment regimens such as those for tuberculosis,
      HIV infections, or cancer. Although drug combination therapy reduces the
      evolution of drug resistance, drug pairs vary in their ability to do so. Thus,
      predictive models are needed to rationally design resistance-limiting therapeutic
      regimens. Using adaptive evolution, we studied the resistance response of the
      common pathogen Escherichia coli to 5 different single antibiotics and all 10
      different antibiotic drug pairs. By analyzing the genomes of all evolved E. coli
      lineages, we identified the mutational events that drive the differences in drug
      resistance levels and found that the degree of resistance development against
      drug combinations can be understood in terms of collateral sensitivity and
      resistance that occurred during adaptation to the component drugs. Then, using
      engineered E. coli strains, we confirmed that drug resistance mutations that
      imposed collateral sensitivity were suppressed in a drug pair growth environment.
      These results provide a framework for rationally selecting drug combinations that
      limit resistance evolution. 

PMID- 25391483
TI  - Semen enhances HIV infectivity and impairs the antiviral efficacy of
      microbicides.
AB  - Topically applied microbicides potently inhibit HIV in vitro but have largely
      failed to exert protective effects in clinical trials. One possible reason for
      this discrepancy is that the preclinical testing of microbicides does not
      faithfully reflect the conditions of HIV sexual transmission. We report that
      candidate microbicides that target HIV components show greatly reduced antiviral
      efficacy in the presence of semen, the main vector for HIV transmission. This
      diminished antiviral activity was dependent on the ability of amyloid fibrils in
      semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of
      microbicides determined in the absence of semen greatly underestimated the drug
      concentrations needed to block semen-exposed virus. One notable exception was
      maraviroc. This HIV entry inhibitor targets the host cell CCR5 co-receptor and
      was highly active against both untreated and semen-exposed HIV. These data help
      to explain why microbicides have failed to protect against HIV in clinical trials
      and suggest that antiviral compounds targeting host factors hold promise for
      further development. These findings also suggest that the in vitro efficacy of
      candidate microbicides should be determined in the presence of semen to identify
      the best candidates for the prevention of HIV sexual transmission. 

PMID- 25391484
TI  - Prevention of preterm birth: harnessing science to address the global epidemic.
AB  - Preterm birth is a leading cause of infant morbidity and mortality worldwide, but
      current interventions to prevent prematurity are largely ineffective. Preterm
      birth is increasingly recognized as an outcome that can result from a variety of
      pathological processes. Despite current research efforts, the mechanisms
      underlying these processes remain poorly understood and are influenced by a range
      of biological and environmental factors. Research with modern techniques is
      needed to understand the mechanisms responsible for preterm labor and birth and
      identify targets for diagnostic and therapeutic solutions. This review evaluates
      the state of reproductive science relevant to understanding the causes of preterm
      birth, identifies potential targets for prevention, and outlines challenges and
      opportunities for translating research findings into effective interventions. 

PMID- 25391485
TI  - Inoculation with arbuscular mycorrhizal fungi improves the nutritional value of
      tomatoes.
AB  - Arbuscular mycorrhizal (AM) fungi can affect many different micronutrients and
      macronutrients in plants and also influence host volatile compound synthesis.
      Their effect on the edible portions of plants is less clear. Two separate studies
      were performed to investigate whether inoculation by AM fungi (Rhizophagus
      irregularis, Funneliformis mosseae, or both) can affect the food quality of
      tomato fruits, in particular common minerals, antioxidants, carotenoids, a suite
      of vitamins, and flavor compounds (sugars, titratable acids, volatile compounds).
      It was found that AM fungal inoculation increased the nutrient quality of tomato
      fruits for most nutrients except vitamins. Fruit mineral concentration increased
      with inoculation (particularly N, P, and Cu). Similarly, inoculated plants had
      fruit with higher antioxidant capacity and more carotenoids. Furthermore, five
      volatile compounds were significantly higher in AM plants compared with non-AM
      controls. Taken together, these results show that AM fungi represent a promising
      resource for improving both sustainable food production and human nutritional
      needs. 

PMID- 25391486
TI  - Ebola outbreak in Conakry, Guinea: epidemiological, clinical, and outcome
      features.
AB  - OBJECTIVES: The authors studied the epidemiological, clinical, and outcome
      features of the Ebola virus disease in patients hospitalized at the Ebola
      treatment center (ETC) in Conakry to identify clinical factors associated with
      death. MATERIALS AND METHODS: A prospective study was conducted from March 25 to
      August 20, 2014. The diagnosis of Ebola virus infection was made on real-time
      PCR. RESULTS: Ninety patients, with a positive test result, were hospitalized.
      Their mean age was 34.12+/-14.29 years and 63% were male patients. Most worked in
      the informal sector (38%) and in the medical and paramedical staff (physicians
      12%, nurses 6%, and laboratory technicians 1%). Most patients lived in the
      Conakry suburbs (74%) and in Boffa (11%). The main clinical signs were physical
      asthenia (80%) and fever (72%). Hemorrhagic signs were observed in 26% of
      patients. The comparison of clinical manifestations showed that hiccups (P=0.04),
      respiratory distress (P=0.04), and hemorrhagic symptoms (P=0.01) were more
      frequent among patients who died. Malaria (72%) and diabetes (2%) were the most
      frequent co-morbidities. The crude case fatality rate was 44% [95% confidence
      interval (33-54%)]. The average hospital stay was 7.96+/-5.81 days. CONCLUSION:
      The first Ebola outbreak in Conakry was characterized by the young age of
      patients, discrete hemorrhagic signs related to lethality. Its control relies on
      a strict use of preventive measures.

PMID- 25391487
TI  - Penicilliosis and AIDS in Haiphong, Vietnam: evolution and predictive factors of
      death.
AB  - OBJECTIVES: The study objective was to assess the lethality rates and the
      predictive factors for death in AIDS patients infected by Penicillium marneffei
      (Pm) in Hai Phong, Vietnam. METHODS: A retrospective cohort study was conducted
      by reviewing 103 medicals records of confirmed cases from June 2006 to August
      2009. RESULTS: Penicilliosis-related mortality was very high (33%). The majors
      risk factors of death were: (i) patient lacking complete treatment, a regimen
      with both of secondary prophylaxis by itraconazole and HAART (OR=52.2, P<0.001);
      (ii) patients having received only secondary prophylaxis (OR=21.2, P<0.001);
      (iii) patients coinfected by hepatitis C (OR=2.3, P=0.02) and tuberculosis
      (OR=1.97, P=0.04). Penicilliosis occurred in 28 cases after initiation of ART,
      probably caused by IRIS, with the same signs and symptoms as "common"
      penicilliosis. However, the diagnosis of IRIS was ruled out because the viral
      load could not be assessed. CONCLUSIONS: Penicilliosis is very frequent in the
      North of Vietnam. A good compliance to a complete treatment with healing
      antifungal (Amphotericin B) then secondary prophylaxis (Itraconazole) associate
      with ART, prolongs survival, prevents relapse, and also allows discontinuing a
      secondary prophylaxis in a half of the cases.

PMID- 25391488
TI  - Evaluation of cross-cultural adaptation and measurement properties of breast
      cancer-specific quality-of-life questionnaires: a systematic review.
AB  - PURPOSE: To assess the procedures of translation, cross-cultural adaptation, and
      measurement properties of breast cancer-specific quality-of-life questionnaires.
      METHODS: Searches were conducted in the databases MEDLINE, EMBASE, CINAHL, and
      SciELO using the keywords: "Questionnaires," "Quality of life," and "Breast
      cancer." The studies were analyzed in terms of methodological quality according
      to the guidelines for the procedure of cross-cultural adaptation and the quality
      criteria for measurement properties of questionnaires. RESULTS: We found 24
      eligible studies. Most of the articles assessed the translation and measurement
      properties of the instrument EORTC QLQ-BR23. Description about translation and
      cross-cultural adaptation was incomplete in 11 studies. Translation and back
      translation were the most tested phases, and synthesis of the translation was the
      most omitted phase in the articles. Information on assessing measurement
      properties was provided incompletely in 23 articles. Internal consistency was the
      most tested property in all of the eligible articles, but none of them provided
      information on agreement. Construct validity was adequately tested in only three
      studies that used the FACT-B and QLQ-BR23. Eight articles provided information on
      reliability; however, only four found positive classification. Responsiveness was
      tested in four articles, and ceiling and floor effects were tested in only three
      articles. None of the instruments showed fully adequate quality. CONCLUSION:
      There is limited evidence on cross-cultural adaptations and measurement
      properties; therefore, it is recommended that caution be exercised when using
      breast cancer-specific quality-of-life questionnaires that have been translated,
      adapted, and tested.

PMID- 25391489
TI  - The potential for a generally applicable mapping model between QLQ-C30 and SF-6D
      in patients with different cancers: a comparison of regression-based methods.
AB  - PURPOSE: To establish and compare generalized or "global" mapping relationships
      between QLQ-C30 and SF-6D, applicable across different cancer types. METHODS:
      Patients (N = 671) with breast, myeloma, colorectal, lymphoma, bone marrow,
      prostate, lung and gastroenteric cancer were randomly split into estimation (75%)
      and validation (25%) datasets. SF-6D was estimated from QLQ-C30 scores via
      ordinary least squares, generalized linear models and median (least-absolute
      deviations) regression approaches, and with Bayesian additive regression kernels.
      Predictive ability was assessed with root mean square error, mean absolute error
      and proportions of predictions with absolute errors >0.05 and >0.1, whereas
      explanatory power with adjusted R (2) or equivalent fit measures. Two external
      samples (breast and colorectal cancer) were used to further test the models.
      RESULTS: The QLQ-C30's global health item, the physical, emotional and social
      functioning scales, and the fatigue, pain and diarrhea symptom scales were
      significant predictors (p < 0.05 or better) in all models. Negligible deviations
      in models' performance were observed. All models overpredicted utilities for
      patients in worst health and underpredicted them for those in better health (p <
      0.01 or better). Regarding external validation, performance was better in the
      colorectal cancer than in the breast cancer sample. CONCLUSIONS: This study has
      provided evidence to support the use of "global" mapping models to predict SF-6D
      utilities from QLQ-C30 in patients with different cancers. Testing with diverse
      patient samples is required to confirm the generalizability (or not) of mapping
      models across cancer conditions.

PMID- 25391490
TI  - The impact of tuberculosis on health utility: a longitudinal cohort study.
AB  - PURPOSE: To estimate health utility derived from the Short Form-36 (SF-36)
      questionnaire and Standard Gamble instrument for persons diagnosed and treated
      for tuberculosis (TB) disease, those diagnosed and treated for latent TB
      infection (LTBI), and those screened but not treated for TB disease or LTBI over
      the year following their diagnosis/initial assessment. METHODS: Participants were
      recruited at two Montreal hospitals (2008-2011) and completed the SF-36 and
      Standard Gamble at baseline and at follow-up visits 1, 2, 4, 6, 9, and 12 months
      thereafter. SF-6D health utility scores were derived from SF-36 responses. Linear
      mixed models were used to compare mean health utility at each evaluation and
      changes in health utility between participants treated for TB disease, those
      treated for LTBI, and those in the control group. RESULTS: Of the 263
      participants, 48 were treated for TB disease, 105 for LTBI, and 110 were control
      participants. Fifty-four percent were women, mean age was 35 years, and 90% were
      foreign-born. Participants treated for TB disease reported worse health utility
      compared with control participants at the baseline visit (mean SF-6D: 0.69 vs.
      0.81; mean Standard Gamble: 0.64 vs. 0.96). They reported successive improvement
      at months 1 and 2 that was then sustained throughout follow-up. Health utility
      reported by participants treated for LTBI and control participants was comparable
      throughout the study. CONCLUSION: Treatment for TB disease had a substantial
      negative impact on health utility, particularly during the first 2 months of
      treatment. However, treatment for LTBI did not have a substantial impact.

PMID- 25391491
TI  - Epstein-Barr virus-specific intrathecal oligoclonal IgG production in relapsing
      remitting multiple sclerosis is limited to a subset of patients and is composed
      of low-affinity antibodies.
AB  - BACKGROUND: The purpose of this study was to investigate intrathecal production
      and affinity distributions of Epstein-Barr virus (EBV)-specific antibodies in
      multiple sclerosis (MS) and controls. METHODS: Cerebrospinal fluid (CSF) and
      serum concentrations, quantitative intrathecal synthesis, oligoclonal bands (OCB)
      patterns and affinity distributions of anti-Epstein Barr virus (EBV) antibodies
      were evaluated in 100 relapsing-remitting MS (RRMS) patients and 200 age- and sex
      matched controls with other inflammatory neurological disorders (OIND) and other
      noninflammatory neurological disorders (NIND). RESULTS: Levels of anti-EBNA-1 and
      anti-viral capsid antigen (VCA) IgG were different in both the CSF (P <0.0001 and
      P <0.01, respectively) and serum (P <0.001 and P <0.05, respectively) among the
      RRMS, OIND and NIND. An intrathecal synthesis of anti-EBNA-1 IgG and anti-VCA
      IgG, as indicated by the antibody index, was underrepresented in the RRMS, OIND
      and NIND (range 1 to 7%). EBV-specific OCB were detected in 24% of the RRMS
      patients and absent in the controls. High-affinity antibodies were more elevated
      in the RRMS and in the OIND than in the NIND for CSF anti-EBNA-1 IgG (P <0.0001)
      and anti-VCA IgG (P <0.0001). After treatment with increasing concentrations of
      sodium thiocyanate, the EBV-specific IgG OCB had low affinity in all 24 RRMS
      patients analyzed. CONCLUSIONS: Our findings do not support the potential role of
      an EBV persistent brain chronic infection in MS and suggest that an EBV-specific
      intrathecal oligoclonal IgG production can occur in a subset of MS patients as
      part of humoral polyreactivity driven by chronic brain inflammation.

PMID- 25391492
TI  - Large-scale analysis of lysine SUMOylation by SUMO remnant immunoaffinity
      profiling.
AB  - Small ubiquitin-related modifiers (SUMO) are evolutionarily conserved ubiquitin
      like proteins that regulate several cellular processes including cell cycle
      progression, intracellular trafficking, protein degradation and apoptosis.
      Despite the importance of protein SUMOylation in different biological pathways,
      the global identification of acceptor sites in complex cell extracts remains a
      challenge. Here we generate a monoclonal antibody that enriches for peptides
      containing SUMO remnant chains following tryptic digestion. We identify 954 SUMO3
      modified lysine residues on 538 proteins and profile by quantitative proteomics
      the dynamic changes of protein SUMOylation following proteasome inhibition. More
      than 86% of these SUMOylation sites have not been reported previously, including
      5 sites on the tumour suppressor parafibromin (CDC73). The modification of CDC73
      at K136 affects its nuclear retention within PML nuclear bodies on proteasome
      inhibition. In contrast, a CDC73 K136R mutant translocates to the cytoplasm under
      the same conditions, further demonstrating the effectiveness of our method to
      characterize the dynamics of lysine SUMOylation. 

PMID- 25391493
TI  - Viability of a Web-Based Module for Teaching Electrocardiogram Reading Skills to
      Psychiatry Residents: Learning Outcomes and Trainee Interest.
AB  - OBJECTIVE: Web-based instruction in post-graduate psychiatry training has shown
      comparable effectiveness to in-person instruction, but few topics have been
      addressed in this format. This study sought to evaluate the viability of a web
      based curriculum in teaching electrocardiogram (EKG) reading skills to psychiatry
      residents. Interest in receiving educational materials in this format was also
      assessed. METHODS: A web-based curriculum of 41 slides, including eight pre-test
      and eight post-test questions with emphasis on cardiac complications of
      psychotropic medications, was made available to all psychiatry residents via
      email. RESULTS: Out of 57 residents, 30 initiated and 22 completed the module.
      Mean improvement from pre-test to post-test was 25 %, and all 22 completing
      participants indicated interest in future web-based instruction. CONCLUSIONS:
      This pilot study suggests that web-based instruction is feasible and under
      utilized as a means of teaching psychiatry residents. Potential uses of web-based
      instruction, such as tracking learning outcomes or patient care longitudinally,
      are also discussed.

PMID- 25391494
TI  - Very-late-antigen-4 (VLA-4)-mediated brain invasion by neutrophils leads to
      interactions with microglia, increased ischemic injury and impaired behavior in
      experimental stroke.
AB  - Neuronal injury from ischemic stroke is aggravated by invading peripheral immune
      cells. Early infiltrates of neutrophil granulocytes and T-cells influence the
      outcome of stroke. So far, however, neither the timing nor the cellular dynamics
      of neutrophil entry, its consequences for the invaded brain area, or the relative
      importance of T-cells has been extensively studied in an intravital setting.
      Here, we have used intravital two-photon microscopy to document neutrophils and
      brain-resident microglia in mice after induction of experimental stroke. We
      demonstrated that neutrophils immediately rolled, firmly adhered, and
      transmigrated at sites of endothelial activation in stroke-affected brain areas.
      The ensuing neutrophil invasion was associated with local blood-brain barrier
      breakdown and infarct formation. Brain-resident microglia recognized both
      endothelial damage and neutrophil invasion. In a cooperative manner, they formed
      cytoplasmic processes to physically shield activated endothelia and trap
      infiltrating neutrophils. Interestingly, the systemic blockade of very-late
      antigen-4 immediately and very effectively inhibited the endothelial interaction
      and brain entry of neutrophils. This treatment thereby strongly reduced the
      ischemic tissue injury and effectively protected the mice from stroke-associated
      behavioral impairment. Behavioral preservation was also equally well achieved
      with the antibody-mediated depletion of myeloid cells or specifically
      neutrophils. In contrast, T-cell depletion more effectively reduced the infarct
      volume without improving the behavioral performance. Thus, neutrophil invasion of
      the ischemic brain is rapid, massive, and a key mediator of functional
      impairment, while peripheral T-cells promote brain damage. Acutely depleting T
      cells and inhibiting brain infiltration of neutrophils might, therefore, be a
      powerful early stroke treatment. 

PMID- 25391495
TI  - Efficacy of computer-assisted, 3D motion-capture toothbrushing instruction.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy of computer
      assisted TBI using a smart toothbrush (ST) and smart mirror (SM) in plaque
      control to that of conventional TBI. MATERIALS AND METHODS: We evaluated the
      plaque removal efficacy of a ST comprising a computer-assisted, wirelessly
      linked, three-dimensional (3D) motion-capture, data-logging, and SM system in
      TBI. We also evaluated the efficacy of TBI with a ST and SM system by analyzing
      the reductions of the modified Quigley-Hein plaque index in 60 volunteers. These
      volunteers were separated randomly into two groups: conventional TBI (control
      group) and computer-assisted TBI (experimental group). The changes in the plaque
      indexes were recorded immediately, 1 week, 1 month, and 10 months after TBI.
      RESULTS: The patterns of decreases in the modified Quigley-Hein plaque indexes
      were similar in the two groups. Reductions of the plaque indexes of both groups
      in each time period were observed (P < 0.0001), and the effects of TBI did not
      differ between the two groups (P = 0.3803). All volunteers were sufficiently
      motivated in using this new system. CONCLUSION: The reported new, computer
      assisted TBI system might be an alternative option in controlling dental plaque
      and maintaining oral hygiene. CLINICAL RELEVANCE: Individuals can be motivated by
      the new system; meanwhile, comparable effects of controlling dental plaque can be
      achieved.

PMID- 25391496
TI  - Evaluation of the effect of bracket-periphery treatment on prevention of enamel
      demineralization by consecutive MUCT scans.
AB  - OBJECTIVES: The aim of this study was to assess the effect of two sealants and
      two varnishes on the prevention of enamel demineralization, as well as the effect
      of inattentive surplus enamel-etching by a self-etching primer (SEP). MATERIALS
      AND METHODS: The sealants ProSeal and Clinpro and the varnishes Protecto and
      FluorProtector were investigated. For inattentive surplus enamel-etching,
      Transbond Plus SEP was used. The teeth (N = 75) underwent a pH-cycling for 4
      weeks and were examined by weekly consecutive MUCT scans (t1-t4) to determine
      mineral loss (DeltaZ Equivalent) and lesion depth (Ld). At t4, we also assessed
      the fluorescence change (DeltaF). RESULTS: For ProSeal, no lesions could be
      detected. In contrast, we found isolated lesions in the area treated with
      Clinpro. Teeth with inattentive surplus enamel-etching showed always a higher
      DeltaZ Eqivalent. However, this was not statistically significantly different
      compared to the teeth treated with the varnishes. The adjacent untreated enamel
      (except the SEP-treated teeth) always showed significantly more demineralization
      than any of the treated areas. The DeltaF partially confirmed these results.
      CONCLUSION: No lesions were shown in the area of application of ProSeal. The
      other materials did not sufficiently protect the enamel; however, a protective
      effect of all materials was obvious when comparing the bracket-periphery with the
      adjacent untreated enamel. Additionally, the area of SEP application showed
      almost always a significantly less demineralization in comparison to that found
      on the adjacent untreated enamel. CLINICAL RELEVANCE: The bracket-periphery was
      not always sufficiently protected. The adjacent untreated enamel did not benefit
      from the bracket-periphery treatment.

PMID- 25391497
TI  - Erratum to: Activity of ivermectin long-acting injectable (IVOMEC((r)) GOLD) in
      first-season grazing cattle exposed to natural challenge conditions in Germany.

PMID- 25391498
TI  - A novel ELISA test for laboratory diagnosis of Blastocystis spp. in human stool
      specimens.
AB  - Detection of Blastocystis is routinely performed by microscopy, culture, and
      formyl-ether (ethyl acetate) concentration technique (FECT). Yet, these methods
      require special skilled personnel, are time consuming, and often involve
      processing that may cause misdiagnosis. The aim of this work is to demonstrate
      the usefulness of a newly introduced ELISA test for the detection of Blastocystis
      antigens in stool samples (CoproELISA(TM) Blastocystis, Savyon Diagnostics) as a
      proper alternative to currently used methods, especially microscopy. A cohort of
      179 fresh/frozen clinical stool samples was tested by the ELISA test, and results
      were compared to consensus methods comprised of microscopic examination of
      Lugol's iodine staining, culture, and immunofluorescence assay (IFA). The new
      ELISA test was able to detect fewer than 10(3) cells, recognized subtypes 1, 2,
      3, and 5 (comprising >95 % of human Blastocystis infections), and exhibited
      similar reactivity when comparing formalin-preserved samples to fresh/frozen
      samples. The test demonstrated 92 % sensitivity, 87 % specificity, and 89 %
      accuracy when culture, and IFA or microscopy consensus results were taken as
      reference. When the consensus was comprised of culture and IFA, the test
      demonstrated sensitivity, specificity, and accuracy of 82, 86, and 84 %,
      respectively. In contrast, the sensitivity of Lugol staining microscopy was only
      18 %. This work presents a unique ELISA test that provides an alternative to the
      use of microscopy, currently most widely used method. The test enables high
      throughput screening and diagnosis of Blastocystis, adaptation to automatic
      procedures.

PMID- 25391499
TI  - The choice of reference genes for assessing gene expression in sugarcane under
      salinity and drought stresses.
AB  - Sugarcane (Saccharum spp. hybrids) is a world-wide cash crop for sugar and
      biofuel in tropical and subtropical regions and suffers serious losses in cane
      yield and sugar content under salinity and drought stresses. Although real-time
      quantitative PCR has a numerous advantage in the expression quantification of
      stress-related genes for the elaboration of the corresponding molecular mechanism
      in sugarcane, the variation happened across the process of gene expression
      quantification should be normalized and monitored by introducing one or several
      reference genes. To validate suitable reference genes or gene sets for sugarcane
      gene expression normalization, 13 candidate reference genes have been tested
      across 12 NaCl- and PEG-treated sugarcane samples for four sugarcane genotypes
      using four commonly used systematic statistical algorithms termed geNorm,
      BestKeeper, NormFinder and the deltaCt method. The results demonstrated that
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and eukaryotic elongation factor
      1-alpha (eEF-1a) were identified as suitable reference genes for gene expression
      normalization under salinity/drought-treatment in sugarcane. Moreover, the
      expression analyses of SuSK and 6PGDH further validated that a combination of
      clathrin adaptor complex (CAC) and cullin (CUL) as reference should be better for
      gene expression normalization. These results can facilitate the future research
      on gene expression in sugarcane under salinity and drought stresses. 

PMID- 25391500
TI  - A novel alkyl hydroperoxidase (AhpD) of Anabaena PCC7120 confers abiotic stress
      tolerance in Escherichia coli.
AB  - In silico analysis together with cloning, molecular characterization and
      heterologous expression reports that the hypothetical protein All5371 of Anabaena
      sp. PCC7120 is a novel hydroperoxide scavenging protein similar to AhpD of
      bacteria. The presence of E(X)11CX HC(X)3H motif in All5371 confers peroxidase
      activity and closeness to bacterial AhpD which is also reflected by its highest
      3D structure homology with Rhodospirillum rubrum AhpD. Heterologous expression of
      all5371 complimented for ahpC and conferred resistance in MJF178 strain
      (ahpCF::Km) of Escherichia coli. All5371 reduced the organic peroxide more
      efficiently than inorganic peroxide and the recombinant E. coli strain following
      exposure to H2O2, CdCl2, CuCl2, heat, UV-B and carbofuron registered increased
      growth over wild-type and mutant E. coli transformed with empty vector.
      Appreciable expression of all5371 in Anabaena sp. PCC7120 as measured by qRT-PCR
      under selected stresses and their tolerance against H2O2, tBOOH, CuOOH and
      menadione attested its role in stress tolerance. In view of the above, All5371 of
      Anabaena PCC7120 emerged as a new hydroperoxide detoxifying protein. 

PMID- 25391501
TI  - [Bilingualism in the Revue des maladies respiratoires: a new step but not a
      revolution].

PMID- 25391502
TI  - Inherited alpha1-antitrypsin deficiency: is the level the key message?

PMID- 25391503
TI  - [Which airway clearance technique for tomorrow?].

PMID- 25391504
TI  - [Epidemiology and COPD screening in France. Workshop from the Societe de
      Pneumologie de Langue Francaise (SPLF)].
AB  - INTRODUCTION: A workshop has been organized in April 2013 by the Societe de
      Pneumologie de Langue Francaise about COPD epidemiology and COPD screening in
      France and other European countries. This article deals with epidemiological data
      and their consequences on the French screening strategy. STATE-OF-THE-ART:
      According to the most recent data, spirometric prevalence of COPD in France is
      7.5% in individuals over 45 years old. During 2000-2002, COPD was responsible for
      1.4% of all causes of death in France and was mentioned to be an associated cause
      of death in 3% of all death certificates. The average medical costs for one COPD
      patient is estimated to be 4366 ?/year, until 7502 ?/year in very severe COPD
      patients. All clinical studies that have been performed in France show that COPD
      screening via mini-spirometry is feasible in general practice or in an ambulatory
      setting; however, a mass screening proved to be difficult to perform. A simple
      technique like the Piko-6((r)) implies a concomitant formalized training. The non
      reimbursement by the French Social Security is also a limiting factor, as the
      absence of medical and economical validation of this strategy. Therefore, COPD
      screening should be focused to individuals at risk and should include tobacco
      issues and cessation. CONCLUSION: COPD screening strategies have to be medically
      evaluated and experiments have to take the specificities of the French health
      organization into consideration. Any COPD screening strategy should be considered
      as an overall fight against the tobacco epidemics.

PMID- 25391505
TI  - [A new fixed dose combination of fluticasone and formoterol in a pressurised
      metered-dose inhaler for the treatment of asthma].
AB  - The combination of an inhaled corticosteroid and a long acting beta-2 agonist is
      indicated for the regular treatment of persistent moderate-to-severe asthmatics
      whose asthma is not controlled by inhaled corticosteroids and the occasional use
      of a short acting beta-2 agonist. The aim of this review is to give an overview
      of the rationale of combining formoterol and fluticasone and to analyze the
      clinical data concerning a new fixed combination of fluticasone and formoterol in
      a pressurised metered-dose inhaler with a dose counter (Flutiform((r))) that was
      approved for the treatment of asthma in France in 2013. The clinical studies
      provide evidence that combined fluticasone/formoterol is more efficacious than
      fluticasone or formoterol given alone, and provides similar improvements in lung
      function to fluticasone (Flixotide((r))) and formoterol (Foradil((r)))
      administered concurrently. The combination of fluticasone/formoterol gave a more
      rapid bronchodilatation than the combination fluticasone/salmeterol. As a whole,
      the combination of fluticasone/formoterol had similar efficacy and tolerability
      profiles to the combinations of either budesonide/formoterol or
      fluticasone/salmeterol.

PMID- 25391506
TI  - [Placebo effect: a contribution of social psychology].
AB  - This article reviews the psychosocial variables, which are of interest in the
      relationship between the patient and the physician. According to a classical
      model of social psychology, such a relationship might contribute to the
      placebo/nocebo effects. We develop herein various relational and contextual
      variables, taking into account four dimensions (intra-individual, interpersonal,
      positional and ideological) and their potential effects on therapeutic responses.
      This applies both in the setting of daily clinical practice and of clinical
      trials. The placebo effect offers an opportunity for collaboration and dialogue
      between social scientists and physicians. 

PMID- 25391507
TI  - [Breaking bad news in oncology: the Belgian experience].
AB  - Breaking bad news is a complex and frequent clinical task for physicians working
      in oncology. It can have a negative impact on patients and their relatives who
      are often present during breaking bad news consultations. Many factors influence
      how the delivery of bad news will be experienced especially the communication
      skills used by physicians. A three-phase process (post-delivery phase, delivery
      phase, pre-delivery phase) has been developed to help physician to handle this
      task more effectively. Communication skills and specific breaking bad news
      training programs are both necessary and effective. A recent study conducted in
      Belgium has shown their impact on the time allocated to each of the three phases
      of this process, on the communication skills used, on the inclusion of the
      relative in the consultation and on physicians' physiological arousal. These
      results underscore the importance of promoting intensive communication skills and
      breaking bad news training programs for health care professionals. 

PMID- 25391508
TI  - Diagnosis of alpha-1 antitrypsin deficiency: modalities, indications and
      diagnosis strategy.
AB  - Alpha-1 antitrypsin (alpha1-AT) deficiency is an autosomal recessive genetic
      disorder, which predisposes affected patients to development of pulmonary
      emphysema or liver cirrhosis. Despite the guidelines from the American Thoracic
      Society and the European Respiratory Society about alpha1-AT deficiency
      screening, it remains significantly under recognized. So, it seems necessary to
      propose an efficient and suitable biological approach to improve diagnosis and
      management of alpha1-AT deficiency. alpha1-AT is a 52 kDa glycoprotein
      predominantly produced in the liver and its physiological serum concentration for
      adults ranges from 0.9 to 2.0g/L (17-39 MUmol/L). It is encoded by the SERPINA1
      gene, which is highly pleomorphic, and to date, more than 100 alleles have been
      identified. alpha1-AT testing would initially involve quantification of serum
      alpha1-AT concentration with possible complementary measurement of the elastase
      inhibitory capacity of serum. If the serum alpha1-AT concentration is reduced
      below the reference value, two strategies for laboratory testing can be used: (i)
      serum alpha1-AT phenotyping by isoelectric focusing which allows identification
      of the most common variant designated as the PI M variant but also of various
      deficient variants besides the predominant PI S and PI Z ones; (ii) genotyping by
      allele-specific PCR methods which allows only identification of the deficient PI
      S and PI Z alleles. Identification of the null alleles or of other rare deficient
      alleles can be performed by direct sequencing of the whole SERPINA1 gene as a
      reflex test.

PMID- 25391509
TI  - [Management of malignant pericardial effusion in lung cancer].
AB  - Acute pericarditis associated with lung cancer is a relatively frequent
      complication but is usually not symptomatic unless it causes tamponade. The
      clinical presentation is classically with dyspnea, thoracic pain, signs of right
      cardiac failure then left cardiac failure and syncope but it is often a difficult
      diagnosis in a patient with multi-symptomatic disease. The diagnosis is based on
      cardiac echography. Toxicity due to radiotherapy or more rarely an infectious
      etiology must be considered. Clinically significant effusions must be drained
      because of the high rate of recurrence after a simple aspiration. Drainage is
      formally indicated when, at echocardiography, the effusion exceeds 20mm in
      diastole, in cases of tamponade or in cases of compromised hemodynamic status.
      The formation of a pericardial window at thoracotomy prevents recurrences. Based
      on old, retrospective, very heterogeneous case series the prognosis, is generally
      considered to be poor with a median survival which does not exceed 100 days and a
      one year survival generally lower than 10%. Prognosis is better where diagnosis
      occurs at an earlier stage allowing regular follow-up and surgical intervention
      in a non-emergency setting.

PMID- 25391510
TI  - [Cardiopulmonary exercise testing and dyspnea in patients with chronic
      respiratory diseases].
AB  - Cardiopulmonary exercise testing (CPET) is the most comprehensive investigation
      for understanding the mechanisms responsible for dyspnea in patients with chronic
      respiratory disease. The two observations presented here illustrate how CPET can
      contribute to the management of patients with interstitial lung diseases. A 60
      year-old woman had been followed for 20 years for non-progressive pulmonary
      sarcoidosis, untreated for many years. CPET led to the diagnosis of an atrial
      septal defect. A 76-year-old man was treated for idiopathic pulmonary fibrosis.
      Before pulmonary rehabilitation, CPET was performed which revealed significant
      aortic valve stenosis, which had been to that point asymptomatic. In these two
      observations, CPET determined the presence of an associated disease, distinct
      from the interstitial lung disease.

PMID- 25391511
TI  - [Maximal isometric voluntary quadriceps strength assessment in COPD].

PMID- 25391512
TI  - [Lung cancer surgery and HIV infection].

PMID- 25391513
TI  - [Haut Conseil de la sante publique (HCSP). Guidance on the live attenuated
      seasonal influenza vaccine FluenzTetra(r) (July 10, 2014)].

PMID- 25391514
TI  - [Extracorporeal life support for patients with acute respiratory distress
      syndrome (adult and paediatric). Consensus conference organized by the French
      Intensive Care Society].

PMID- 25391515
TI  - The change in Ig regulation from children to adults disconnects the correlation
      with the 3'RR hs1.2 polymorphism.
AB  - BACKGROUND: In the immune system, the serum levels of immunoglobulin (Ig)
      increase gradually during ageing. Through B cell development, the Ig heavy chain
      expression is modulated by a regulatory region at the 3' of the constant alpha
      gene (3'RR), in single copy in rodents and, due to a large duplication, in two
      copies in apes. The human 3'RR1 and 3'RR2 are both characterized by three
      enhancers, the central of which, namely hs1.2, is highly polymorphic. Human hs1.2
      has four different variants with unique binding sites for transcription factors
      (e.g. NF-kB and SP1) and shows variable allelic frequencies in populations with
      immune disorders. In previous works, we have reported that in several autoimmune
      diseases the *2 allele of hs1.2 is genetically associated to high level of IgM in
      peripheral blood. In subjects with altered levels of circulating Ig, an increased
      level was associated to *2 allele of hs1.2 and low levels corresponded to high
      frequency of *1 allele. RESULTS: We have correlated the allelic frequencies of
      hs1.2 with IgM, IgG and IgA serum concentrations in two cohorts of healthy people
      of different age and after three years follow-up in children homozygous for the
      allele. Here we show that when the expression levels of Ig in children are low
      and medium, the frequencies of *1 and *2 alleles are the same. Instead, when the
      Ig expression levels are high, there is a significantly higher frequency of the
      allele *2. The follow-up of children homozygous for *1 and *2 alleles showed that
      the increase or decrease of circulating Ig was not dependent on the number of
      circulating mature B cells. CONCLUSIONS: These data support the idea that under
      physiologic condition there is a switch of regulative pathways involved in the
      maturation of Ig during ageing. This mechanism is evidenced by hs1.2 variants
      that in children but not in adults participate to Ig production, coordinating the
      three class levels.

PMID- 25391516
TI  - Epigenetics of hyper-responsiveness to allergen challenge following intrauterine
      growth retardation rat.
AB  - BACKGROUND: Epidemiological studies have revealed that intrauterine growth
      retardation (IUGR) or low birth weight is linked to the later development of
      asthma. Epigenetic regulatory mechanisms play an important role in the fetal
      origins of adult disease. However, little is known regarding the correlation
      between epigenetic regulation and the development of asthma following IUGR.
      METHODS: An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used
      to study whether epigenetic mechanisms play a role in the development of asthma
      following IUGR. RESULTS: Maternal nutrient restriction increased histone
      acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of
      offspring, but did not cause significant alterations of DNA methylation. The
      effect was maintained until 10 weeks after birth. Furthermore, these epigenetic
      changes may have induced IUGR individuals to be highly sensitive to OVA challenge
      later in life, resulting in more significant changes related to asthma.
      CONCLUSIONS: These findings suggest that epigenetic mechanisms might be closely
      associated with the development of asthma following IUGR, providing further
      insight for improved prevention of asthma induced by environmental factors.

PMID- 25391517
TI  - UK's plan to build community care centres for Ebola patients is questioned.

PMID- 25391518
TI  - Right ventricular function in heart failure with preserved ejection fraction: a
      community-based study.
AB  - BACKGROUND: The prevalence and clinical significance of right ventricular (RV)
      systolic dysfunction (RVD) in patients with heart failure and preserved ejection
      fraction (HFpEF) are not well characterized. METHODS AND RESULTS: Consecutive,
      prospectively identified HFpEF (Framingham HF criteria, ejection fraction >=50%)
      patients (n=562) from Olmsted County, Minnesota, underwent echocardiography at HF
      diagnosis and follow-up for cause-specific mortality and HF hospitalization. RV
      function was categorized by tertiles of tricuspid annular plane systolic
      excursion and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2
      dimensional assessment. Whether RVD was defined by semiquantitative assessment or
      tricuspid annular plane systolic excursion <=15 mm, HFpEF patients with RVD were
      more likely to have atrial fibrillation, pacemakers, and chronic diuretic
      therapy. At echocardiography, patients with RVD had slightly lower left
      ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure
      and cardiac output, higher pulmonary artery systolic pressure, and more severe RV
      enlargement and tricuspid valve regurgitation. After adjustment for age, sex,
      pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by
      semiquantitative assessment was associated with higher all-cause (hazard
      ratio=1.35; 95% confidence interval, 1.03-1.77; P=0.03) and cardiovascular
      (hazard ratio=1.85; 95% confidence interval, 1.20-2.80; P=0.006) mortality and
      higher first (hazard ratio=1.99; 95% confidence interval, 1.35-2.90; P=0.0006)
      and multiple (hazard ratio=1.81; 95% confidence interval, 1.18-2.78; P=0.007) HF
      hospitalization rates. RVD defined by tricuspid annular plane systolic excursion
      values showed similar but weaker associations with mortality and HF
      hospitalizations. CONCLUSIONS: In the community, RVD is common in HFpEF patients,
      is associated with clinical and echocardiographic evidence of more advanced HF,
      and is predictive of poorer outcomes.

PMID- 25391520
TI  - Challenges and importance of finding hidden confounders when conducting
      comparative effectiveness studies using registry data: the impact of surgical
      turn-down on percutaneous coronary intervention mortality.

PMID- 25391519
TI  - Surgical ineligibility and mortality among patients with unprotected left main or
      multivessel coronary artery disease undergoing percutaneous coronary
      intervention.
AB  - BACKGROUND: Decisions to proceed with surgical versus percutaneous
      revascularization for multivessel coronary artery disease are often based on
      subtle clinical information that may not be captured in contemporary registries.
      The present study sought to evaluate the association between surgical
      ineligibility documented in the medical record and long-term mortality among
      patients with unprotected left main or multivessel coronary artery disease
      undergoing percutaneous coronary intervention. METHODS AND RESULTS: All subjects
      undergoing nonemergent percutaneous coronary intervention for unprotected left
      main or multivessel coronary artery disease were identified at 2 academic medical
      centers from 2009 to 2012. Documentation of surgical ineligibility was assessed
      through review of electronic medical records. Cox proportional hazard models
      adjusted for known mortality risk factors were created to assess long-term
      mortality in patients with and without documentation of surgical ineligibility.
      Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were
      deemed ineligible for coronary artery bypass graft surgery. The most common
      explicitly cited reasons for surgical ineligibility in the medical record were
      poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%).
      After adjustment for known risk factors, documentation of surgical ineligibility
      remained independently associated with an increased risk of in-hospital (odds
      ratio, 6.26; 95% confidence interval, 2.16-18.15; P<0.001) and long-term
      mortality (hazard ratio, 2.98; 95% confidence interval, 1.88-4.72, P<0.001) after
      percutaneous coronary intervention. CONCLUSIONS: Documented surgical
      ineligibility is common and associated with significantly increased long-term
      mortality among patients undergoing percutaneous coronary intervention with
      unprotected left main or multivessel coronary disease, even after adjustment for
      known risk factors for adverse events during percutaneous revascularization.

PMID- 25391521
TI  - It is time to look at heart failure with preserved ejection fraction from the
      right side.

PMID- 25391523
TI  - A rare spontaneous enterocutaneous fistula.
AB  - A 70-year-old woman presented with a short history of a spontaneous
      enterocutaneos fistula in the left inguinal region. A laparotomy revealed a
      fistulizing Richter's hernia. The fistulizing small bowel segment was resected
      and the femoral hernia repaired from below. Although rare, a complicating
      Richter's hernia should be considered in the differential diagnosis of a groin
      fistula. 

PMID- 25391522
TI  - Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the
      Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest: a
      statement for healthcare professionals from a task force of the International
      Liaison Committee on Resuscitation (American Heart Association, European
      Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart
      and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation
      Council of Southern Africa, Resuscitation Council of Asia); and the American
      Heart Association Emergency Cardiovascular Care Committee and the Council on
      Cardiopulmonary, Critical Care, Perioperative and Resuscitation.
AB  - Utstein-style guidelines contribute to improved public health internationally by
      providing a structured framework with which to compare emergency medical services
      systems. Advances in resuscitation science, new insights into important
      predictors of outcome from out-of-hospital cardiac arrest, and lessons learned
      from methodological research prompted this review and update of the 2004 Utstein
      guidelines. Representatives of the International Liaison Committee on
      Resuscitation developed an updated Utstein reporting framework iteratively by
      meeting face to face, by teleconference, and by Web survey during 2012 through
      2014. Herein are recommendations for reporting out-of-hospital cardiac arrest.
      Data elements were grouped by system factors, dispatch/recognition, patient
      variables, resuscitation/postresuscitation processes, and outcomes. Elements were
      classified as core or supplemental using a modified Delphi process primarily
      based on respondents' assessment of the evidence-based importance of capturing
      those elements, tempered by the challenges to collect them. New or modified
      elements reflected consensus on the need to account for emergency medical
      services system factors, increasing availability of automated external
      defibrillators, data collection processes, epidemiology trends, increasing use of
      dispatcher-assisted cardiopulmonary resuscitation, emerging field treatments,
      postresuscitation care, prognostication tools, and trends in organ recovery. A
      standard reporting template is recommended to promote standardized reporting.
      This template facilitates reporting of the bystander-witnessed, shockable rhythm
      as a measure of emergency medical services system efficacy and all emergency
      medical services system-treated arrests as a measure of system effectiveness.
      Several additional important subgroups are identified that enable an estimate of
      the specific contribution of rhythm and bystander actions that are key
      determinants of outcome. 

PMID- 25391524
TI  - In vitro anti-inflammatory effects of citrulline on peritoneal macrophages in
      Zucker diabetic fatty rats.
AB  - In type 2 diabetes (T2D) macrophage dysfunction increases susceptibility to
      infection and mortality. This may result from the associated decreased plasma
      concentration of arginine, an amino acid that plays an important role in
      immunity. In vitro, increasing arginine availability leads to an improvement in
      macrophage function; however, arginine supplementation in diabetic obese patients
      may be detrimental. The aim of the present study was to assess in vitro whether
      citrulline, an arginine precursor, could replace arginine in the regulation of
      macrophage function under a condition of diabetes and obesity. Peritoneal
      macrophages from diabetic obese or lean rats were incubated for 6 h in an
      arginine-free medium, in the presence of increasing citrulline concentrations
      (0.1, 0.5, 1 or 2 mmol/l). Cytokine and NO production was determined. Peritoneal
      macrophages from either lean or diabetic obese rats produced NO, and at higher
      levels in the cells from lean rats. In diabetic obese rats, TNF-alpha production
      decreased with increasing citrulline concentrations, but was higher than that in
      the cells from lean rats. In contrast, IL-6 production increased with increasing
      citrulline concentrations. The present experiment shows that citrulline is
      effectively used for NO production and regulates cytokine production in
      macrophages from diabetic obese rats. This effect warrants in vivo evaluation in
      T2D-related inflammation.

PMID- 25391525
TI  - Therapeutic strategies for relapsing-remitting multiple sclerosis: a special
      focus on reduction of grey matter damage as measured by brain atrophy.
AB  - In the past two decades, several pathological and radiological findings
      convincingly demonstrated that damage of the cortical and deep grey matter is a
      key issue in multiple sclerosis with a significant impact on physical and
      cognitive disability. Moreover, it has become increasingly evident that the
      effect of available therapies on the inflammatory white matter damage is not a
      guarantee of a meaningful effect on the neurodegenerative process mainly
      affecting the grey matter. Despite the efficacy of all approved disease-modifying
      drugs should be measured considering such a relevant aspect of the disease, data
      from clinical trials are few, scattered and heterogeneous. The aim of this review
      is to summarize the evidence so far acquired on the effect of reducing grey
      matter damage produced by current and emerging disease-modifying therapies for
      multiple sclerosis. 

PMID- 25391526
TI  - Mini symposium: a controversy between geneticists and biologists.

PMID- 25391527
TI  - Is the Kinect system suitable for evaluation of the hip joint range of motion and
      as a screening tool for femoroacetabular impingement (FAI)?
AB  - BACKGROUND: In the clinical evaluation of femoroacetabular impingement (FAI),
      there is a lack of quantitative, reliable and informative assessment methods for
      the overall functional capability of an individual. OBJECTIVE: We compared
      clinical and radiological measurements of the hip joint with a new methodology
      based on the concept of 3-dimensional reachable workspace using Microsoft Kinect.
      METHODS: We assessed the correlation between the alpha angle of Notzli on full
      length radiographs and the clinical internal rotation. We evaluated the accuracy
      of joint positions and angles of the hip between the Kinect system and clinical
      examination including range of motion (ROM). RESULTS: The results of our clinical
      trial with 24 study participants showed a significant difference between normal
      internal rotation (> 21 degrees ) and reduced internal rotation (? 21 degrees )
      in comparison to the radiological alpha angle of Notzli (P=0.026). The acquired
      reachable Kinect data demonstrated a moderate agreement between the Kinect and
      clinical examination (correlation coefficients between 0.230 and 0.375).
      CONCLUSIONS: The findings suggest that a higher grade alpha angle of Notzli
      accompanies reduced clinical internal rotation. The Kinect system provides
      reliable results of hip ROM. However, further test series must be performed for
      the application of Kinect in the clinical evaluation of FAI.

PMID- 25391528
TI  - Biomechanical study of plantar pressures during walking in male soccer players
      with increased vs. normal hip alpha angles.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) is accompanied by increased hip
      alpha angles, in particular in athletes with high impact sports. OBJECTIVE: The
      aim of our study was to investigate the dynamic function of the foot during
      walking in male soccer players with increased versus normal alpha angles.
      METHODS: Plantar pressures of 20 injury-free male soccer players were recorded
      during barefoot walking at 1.6 m/s. Ten subjects had bilaterally increased (>55
      degrees ) (IA) and ten subjects normal (<50 degrees ) hip alpha angles (NA). Both
      standing and kicking leg were analyzed. RESULTS: Compared to NA, IA showed lower
      force-time-integrals (-23%; p< 0.01), pressure-time-integrals (-29%; p< 0.001)
      and relative loads (p< 0.05) under the heel. In IA contact area of the hallux is
      about 13% (p< 0.05) reduced. In IA relative loads are increased under the lateral
      midfoot (p< 0.05) and the second toe (p< 0.05). Higher loading of the lateral
      midfoot is also reflected in the increased force-time integral (+33%; p< 0.001).
      No differences between legs and no interactions, indicating a specifity in
      kicking or standing leg, are found. CONCLUSIONS: Compared to NA, soccer players
      with IA show a forward shifting of the center of pressure which indicates a
      compensatory mechanism of the foot during walking.

PMID- 25391529
TI  - Design and analysis of finite element based sensors for diagnosis of liver
      disorders using biocompatible metals.
AB  - BACKGROUND: Analysis of liver tissue in normal and abnormal conditions is
      essential for disease research, medical device design and treatment planning.
      Currently cirrhosis and malignancies of liver are among the major causes of
      mortality, worldwide. OBJECTIVE: The objective of this work is to design an
      efficient capacitive sensor using Finite Element Methods (FEM), for diagnosis of
      cirrhotic and malignant liver. METHODS: In this work, 3D geometric FEM models
      (N=120) of normal, cirrhotic and malignant liver were generated using Comsol
      3.5a. A set of 'E' shaped metallic plates, each with a dimension of 1 * 1 * 1 mm
      were modeled and mounted on the developed liver models. Four different bio
      compatible metals namely Gold, Silver, Palladium and Platinum were used for
      analysis. Further, the observed capacitance values were converted into voltage
      using a De Sauty's bridge circuit implemented using Proteus 8. Finally, the
      statistical significance of the results was analyzed using the ANOVA test.
      RESULTS: Results demonstrate that the observed voltages show significant
      variations between different liver pathologies. The developed sensor
      characteristic was found to be linear and the sensitivity of the sensor was found
      to be high when platinum electrodes were used. The diagnostic ability of the
      developed sensors for the adopted biocompatible metals was found to be highly
      statistically significant (P < 0.001). CONCLUSIONS: The proposed sensor design is
      compact with small dimensions and can be placed in contact with the human liver
      using endoscopic techniques. Hence, the developed sensor may provide a minimally
      invasive technique for liver diagnosis. This study appears to be of high clinical
      relevance since modelling of normal and abnormal liver, as well as design of
      suitable sensors for identification of liver abnormalities is required for
      improving the present diagnostic techniques.

PMID- 25391531
TI  - Changes in blood flow due to stented parent artery expansion in an intracranial
      aneurysm.
AB  - BACKGROUND: Stent placement is thought to obstruct the inflow of blood to an
      aneurysm. However, we introduced parent artery expansion and demonstrated that
      this may reduce the blood flow by the stent. In our previous study using
      idealized shapes, the results showed that flow reduction was greater than 22.2%,
      even if the expansion rate was only 6%. Furthermore, the parent artery expansion
      is predominantly caused by the effect of flow reduction as compared to that of
      flow reduction due to the obstruction of flow under stent placement. However, a
      realistic shape is complex and the blood flow also becomes complex flow. It is
      not understood whether the results of flow in the idealized shape are reflective
      of flow from a realistic 3D model. Therefore, we examined the effect of parent
      artery expansion using a realistic model. OBJECTIVE: The aim is to clarify the
      effects of parent artery expansion on inflow rate, wall shear stress, and
      oscillatory shear index. METHODS: We used a patient-specific geometry of a human
      internal carotid artery with an aneurysm. The geometry of parent artery expansion
      due to oversized stent constructed based on the voronoi diagram. We performed
      calculations in the unsteady-state situations using constructed models. RESULTS:
      The complexity of the flow in the aneurysm decreases in case of expanded parent
      artery. The inflow rate decreases by 33.6% immediately after parent artery
      expansion alone without a stent. The effect of the parent artery expansion on
      flow reduction is larger than that of the obstruction flow by stent placement. In
      addition, wall shear stress and oscillatory shear index on the aneurysm wall
      decrease by change in blood flow due to the parent artery expansion. CONCLUSION:
      The effects of the parent artery expansion in a realistic aneurysm model with
      different stent lengths were evaluated on the basis of a numerical simulation.
      Although the flow was complex, the parent artery expansion with stent reduces the
      inflow to the aneurysm and wall shear stress and oscillatory shear index on the
      aneurysm. Therefore, we suggest that changes in the blood flow because of the
      parent artery expansion may be identified and, sometimes, is more effective than
      the obstruction flow due to the stent placement.

PMID- 25391530
TI  - Kinetic therapy in multiple trauma patients with severe blunt chest trauma: an
      analysis at a level-1 trauma center.
AB  - BACKGROUND AND OBJECTIVES: Chest trauma is a relevant risk factor for mortality
      after multiple trauma. Kinetic therapy (KT) represents a potential treatment
      option in order to restore pulmonary function. Decision criteria for performing
      kinetic therapy are not fully elucidated. The purpose of this study was to
      investigate the decision making process to initiate kinetic therapy in a well
      defined multiple trauma cohort. METHODS: A retrospective analysis (2000-2009) of
      polytrauma patients (age > 16 years, ISS ? 16) with severe chest trauma
      (AIS(Chest) ? 3) was performed. Patients with AIS(Head) ? 3 were excluded.
      Patients receiving either kinetic (KT+) or lung protective ventilation strategy
      (KT-) were compared. Chest trauma was classified according to the AIS(Chest),
      Pulmonary Contusion Score (PCS), Wagner Jamieson Score and Thoracic Trauma
      Severity Score (TTS). There were multiple outcome parameters investigated
      included mortality, posttraumatic complications and clinical data. A multivariate
      regression analysis was performed. RESULTS: Two hundred and eighty-three patients
      were included (KT+: n=160; KT-: n=123). AIS(Chest), age and gender were
      comparable in both groups. There were significant higher values of the ISS, PCS,
      Wagner Jamieson Score and TTS in group KT+. The incidence of posttraumatic
      complications and mortality was increased compared to group KT- (p< 0.05).
      Despite that, kinetic therapy failed to be an independent risk factor for
      mortality in multivariate logistic regression analysis. CONCLUSIONS: Kinetic
      therapy is an option in severely injured patients with severe chest trauma.
      Decision making is not only based on anatomical aspects such as the AIS(Chest),
      but on overall injury severity, pulmonary contusions and physiological
      deterioration. It could be assumed that the increased mortality in patients
      receiving KT is primarily caused by these factors and does not reflect an
      independent adverse effect of KT. Furthermore, KT was not shown to be an
      independent risk factor for mortality.

PMID- 25391532
TI  - Establishing a Hierarchy for the Two Components of Restricted Activity.
AB  - BACKGROUND: Increasing evidence suggests that illnesses and injuries leading to
      restricted activity have adverse functional consequences, but whether the two
      components of restricted activity have comparable effects is unknown. We
      evaluated whether an illness/injury leading to bed rest represents a more potent
      exposure than one leading to cutting down on one's usual activities without bed
      rest. METHODS: We prospectively evaluated 754 community-living persons, 70+
      years. Telephone interviews were completed monthly for >15 years to assess
      disability in four basic, five instrumental, and four mobility activities and to
      ascertain exposure to illnesses/injuries leading to cut down activities and bed
      rest, respectively. For each of the three functional domains, transitions between
      no disability, mild disability, and severe disability were evaluated each month.
      RESULTS: For each domain, cut down activities and bed rest were significantly
      associated with at least one transition. The associations were consistently
      stronger, however, for bed rest than for cut down activities. Bed rest was a
      particularly potent exposure for transitions from no disability to severe
      disability, with hazard ratios as high as 8.94 (95% CI, 5.69-14.1) for the
      mobility activities, and for all transitions from severe disability (representing
      recovery), with hazard ratios as low as 0.25 (0.12-0.54) for the transition to no
      disability for the basic activities. CONCLUSIONS: In the setting of an
      illness/injury, bed rest was more strongly associated with a set of clinically
      meaningful transitions in functional status than cut down activities. Prompt
      medical attention may be warranted when an older person takes to bed because of
      an illness/injury.

PMID- 25391533
TI  - Discovery of 9,10-Dihydroacridines as Novel Class of ABCB1 Inhibitors.
AB  - Nonplanar 9,10-dihydroacridines were synthesized as promising C2 symmetric
      molecular scaffolds as inhibitors of the transmembrane efflux pump ABCB1. Within
      the series structure-activity relationships are discussed revealing the
      importance of hydrogen bond acceptor functions. A selectivity of ABCB1 inhibition
      is demonstrated for selected candidates and a bioanalytical study proved
      nontoxicity as well as missing ABCB1 substrate properties. The results encourage
      to further develop the promising class of ABCB1 inhibitors. 

PMID- 25391534
TI  - Dietary fibres in the nutrition of the growing rabbit and recommendations to
      preserve digestive health: a review.
AB  - The importance of dietary fibre fractions in animal feeding is due to its
      influence on the rate of passage, mucosal functionality and its role as substrate
      for gut microbiota that relates to performance and digestive health. The
      complexity of the physical structure and chemical composition of polysaccharides
      in plant cell walls explains the wide and different physiological effects of this
      large range of fibre fractions. Our review will first briefly consider the
      definition and structure of the different classes of fibres and of cell wall
      constituents, followed by a description of some analytical methods employed for
      monogastric feeds. Second, the nutritional role and impact of fibre intake on
      digestive health will be described for the growing rabbit with an extensive
      analysis of previous studies performed without antibiotics. The fibres in rabbit
      feed are essential for reducing the risk of digestive trouble after weaning, and
      the requirements are defined in terms of the quantity and quality of the fibre
      fractions as follows: a minimal dietary level of lignocellulose 'ADF' (18%) and
      lignins (>5%), balanced with a maximum quantity of digestible fibres 'DgF' (ratio
      DgF/ADF below 1.3). Soluble fibres, defined as the difference between total
      dietary fibre and NDF, are quickly fermented and digested by the rabbit. However,
      their impact on digestive health is still questioned. 

PMID- 25391535
TI  - Pathogenicity of border disease virus FNK2012-1 strain isolated from a pig in the
      natural host, sheep.
AB  - A first isolation of border disease virus (BDV) in Japan was from a pig on a farm
      without keeping any ruminants. Our previous study showed that this BDV, termed
      the FNK2012-1 strain, replicated inefficiently in swine-derived cells compared
      with those of ruminant origin. Pigs inoculated with this virus showed neither
      clinical symptoms nor viremia. In this study, we evaluated the pathogenicity of
      the FNK2012-1 strain in sheep, its natural host. The inoculated sheep showed
      clinical symptoms and transient viremia. Seroconversion was observed in the
      inoculated sheep. These results suggest that the FNK2012-1 strain was introduced
      from sheep and has not yet adapted to swine. Therefore, surveillance of border
      disease in Japan is necessary among both the swine and ruminant populations. 

PMID- 25391536
TI  - Congenital malformation of the vaginal orifice, imperforate vagina, in the common
      marmoset (Callithrix jacchus).
AB  - The following is a report on a congenital vaginal malformation, imperforate
      vagina, in the common marmoset (Callithrix jacchus). This anomaly was observed
      for the first time in an adult female in our research colony. There was no
      uterine and vaginal aplasia or atresia in her grossly normal genital tract. The
      plasma progesterone concentration suggested that the ovarian cycle had ceased.
      However, this may not be related to a functional anomaly, but rather to
      suppressed ovulation resulting from subordination to cagemates considering the
      various stages of follicular development observed. 

PMID- 25391538
TI  - Creation of superwetting surfaces with roughness structures.
AB  - In this work, we explored the possibility of creating superwetting surfaces,
      which are defined here as those with apparent contact angles of <5 degrees ,
      using roughness structures for the purpose of eliminating the surface tension
      effect on a floating small plate, which is denser than the surrounding liquid.
      The roughness ratio is often thought to play a critical role in generating
      superwetting surfaces. However, we found that the top surface ratio had more
      influence on apparent contact angles. When this ratio was <0.013, the resulting
      apparent contact angle might be less than 5 degrees , when the intrinsic contact
      angle was >=40 degrees . Accordingly, hybrid micro- and nanostructures, which had
      such a small ratio, were chosen to create the superwetting surfaces. These
      surfaces were subsequently applied to eliminate the surface tension effect on a
      small plate. As a result of this elimination, the small plate sank down to the
      bottom of the liquid. 

PMID- 25391537
TI  - Complementary medicine in nursing homes--results of a mixed methods pilot study.
AB  - BACKGROUND: 'Kneipp Therapy' (KT) is a form of Complementary and Alternative
      Medicine (CAM) that includes a combination of hydrotherapy, herbal medicine, mind
      body medicine, physical activities, and healthy eating. Since 2007, some nursing
      homes for older adults in Germany began to integrate CAM in the form of KT in
      care. The study investigated how KT is used in daily routine care and explored
      the health status of residents and caregivers involved in KT. METHODS: We
      performed a cross-sectional pilot study with a mixed methods approach that
      collected both quantitative and qualitative data in four German nursing homes in
      2011. Assessments in the quantitative component included the Quality of Life in
      Dementia (QUALIDEM), the Short Form 12 Health Survey (SF-12), the Barthel-Index
      for residents and the Work Ability Index (WAI) and SF-12 for caregivers. The
      qualitative component addressed the residents' and caregivers' subjectively
      experienced changes after integration of KT. It was conceptualized as an
      ethnographic rapid appraisal by conducting participant observation and semi
      structured interviews in two of the four nursing homes. RESULTS: The quantitative
      component included 64 residents (53 female, 83.2 +/- 8.1 years (mean and SD)) and
      29 caregivers (all female, 42.0 +/- 11.7 years). Residents were multimorbid (8 +/
      3 diagnoses), and activities of daily living were restricted (Barthel-Index 60.6
      +/- 24.4). The caregivers' results indicated good work ability (WAI 37.4 +/-
      5.1), health related quality of life was superior to the German sample (SF-12
      physical CSS 49.2 +/- 8.0; mental CSS 54.1 +/- 6.6). Among both caregivers and
      residents, 89% considered KT to be positive for well-being.The qualitative
      analysis showed that caregivers perceived emotional and functional benefits from
      more content and calmer residents, a larger variety in basic care practices, and
      a more self-determined scope of action. Residents reported gains in attention and
      caring, and recognition of their lay knowledge. CONCLUSION: Residents showed
      typical characteristics of nursing home inhabitants. Caregivers demonstrated good
      work ability. Both reported to have benefits from KT. The results provide a good
      basis for future projects, e.g. controlled studies to evaluate the effects of CAM
      in nursing homes.

PMID- 25391539
TI  - The GH receptor exon 3 deleted/full-length polymorphism is associated with
      central adiposity in the general population.
AB  - OBJECTIVE: To test the hypothesis that the GH receptor (GHR) exon 3 deleted
      (d3)/full-length (fl) polymorphism influences anthropometry and body composition
      in the general population. DESIGN AND SETTING: The Swedish Obese Subjects (SOS)
      reference study is a cross-sectional population-based study, randomly selected
      from a population registry. A subgroup of the population-based Malmo Diet and
      Cancer study (MDC-CC) was used as a replication cohort. METHODS: The SOS
      reference study comprises 1135 subjects (46.2% men), with an average age of 49.5
      years. The MDC-CC includes 5451 successfully genotyped subjects (41.5% men), with
      an average age of 57.5 years. GHR d3/fl genotypes were determined using TagSNP
      rs6873545. Linear regression analyses were used to test for genotype-phenotype
      associations. RESULTS: In the SOS reference study, subjects homozygous for the d3
      GHR weighed ~4 kg more (P=0.011), and had larger waist-to-hip ratio (WHR,
      P=0.036), larger waist circumference (P=0.016), and more fat-free mass estimated
      from total body potassium (P=0.026) than grouped fl/d3 and fl/fl subjects (d3
      recessive genetic model). The association with WHR was replicated in the MDC-CC
      (P=0.002), but not those with other anthropometric traits. CONCLUSIONS: In this
      population-based study, the GHR d3/fl polymorphism was found to be of functional
      relevance and associated with central adiposity, such that subjects homozygous
      for the d3-GHR showed an increased abdominal obesity.

PMID- 25391540
TI  - Lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review
      of the literature.
AB  - Lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) is a rare acquired
      disorder caused by prothrombin antibodies. The disease is most common in the
      pediatric age group (<16 years), and more prevalent in women. There are well
      established clinical diseases associated with LA-HPS, most notably systemic lupus
      erythematosus (SLE) and viral infections. The clinical manifestation of LA-HPS
      varies greatly in severity and it may cause severe life-threatening bleeding
      diathesis. LA-HPS is to be suspected when a patient presents with bleeding and a
      prolonged activated partial thromboplastin and prothrombin time, in combination
      with a lupus anticoagulant. The diagnosis is confirmed in the laboratory by
      identification of reduced prothrombin levels. There are no standardized
      recommendations for treatment of the hemorrhage associated with the syndrome;
      corticosteroids are used as first-line treatment. This review summarizes what is
      currently known about the pathogenesis, clinical features, diagnosis, treatment
      and prognosis of LA-HPS, and presents two case reports. 

PMID- 25391541
TI  - Lupus enteritis: clinical characteristics and predictive factors for recurrence.
AB  - OBJECTIVES: To compare the clinical characteristics of lupus enteritis (LE) and
      non-enteric lupus (non-LE) patients and identify predictors of LE recurrence.
      METHODS: We retrospectively reviewed the medical records of 62 systemic lupus
      erythematosus (SLE) patients in a tertiary hospital who experienced enteric
      symptoms and underwent abdominal computed tomography scanning between January
      1997 and December 2013. We compared the clinical characteristics between LE and
      non-LE patients and between recurrent LE and non-recurrent LE cases. RESULTS: Out
      of 62 SLE patients with enteric symptoms, 46 cases (74%) were compatible with LE
      based on computed tomography findings. The C4 level was decreased in the LE group
      compared with the non-LE group (9.0 +/- 5.6 vs. 12.3 +/- 6.2, p = 0.032).
      Recurrence of LE was observed in 14 patients (28%). Initial involvement at the
      colon (79% vs. 41%, p = 0.026) and bladder with/without the ureter was more
      common in the recurrent group (57% vs. 25%, p = 0.048). By multivariate analysis,
      the hazard ratios of variables associated with recurrence were 4.689 for colon
      involvement (95% confidence interval: 1.245-17.659, p = 0.0220] and 5.468 for
      cystitis with/without ureteritis (95% confidence interval: 1.629-18.360, p =
      0.006). CONCLUSION: Colon and urinary tract involvement in LE patients may be
      associated with the recurrence of LE.

PMID- 25391542
TI  - Biomarkers identified from serum proteomic analysis for the differential
      diagnosis of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves
      different organs. Its most important feature is the production of specific
      autoantibodies against nuclear or cytoplasmic antigens. Proteomic analysis of
      serum, as one of the most readily available body fluids, can be used as a method
      for clarifying the pathogenesis of SLE. In this study the serum proteome of 13
      patients with SLE was evaluated and compared with seven healthy control
      participants. A specific kit was used to remove high-abundance proteins. After
      depletion, the protein expression patterns created by two-dimensional gel
      electrophoresis (2-DE) and MALDI-TOF/TOF-MS were used to identify disease
      associated proteins. We found differential expression of 15 protein spots,
      including seven up-regulated and eight down-regulated proteins in SLE samples, in
      comparison with healthy participants. These spots were identified by MALDI
      TOF/TOF-MS and classified into three groups include keratins, apolipoproteins and
      albumin, and individual proteins such as transthyretin, haptoglobin and
      prothrombin. These findings can help to clarify the pathophysiology and mechanism
      of SLE. 

PMID- 25391544
TI  - Ovarian reserve in antiphospholipid syndrome: the jury is still out.

PMID- 25391543
TI  - Predictors of the response to treatment in acute lupus hemophagocytic syndrome.
AB  - OBJECTIVE: The objective of this paper is to identify predictors for the response
      to treatment of acute lupus hemophagocytic syndrome (ALHS). METHODS: We reviewed
      seven cases with ALHS admitted to our hospital and published ALHS cases
      identified in the 2001-2014 Medline database, and then conducted univariate and
      multivariate analyses to identify predictors for the response to treatment.
      RESULTS: Review of our cases showed a significant and negative correlation
      between serum ferritin and anti-DNA antibody (p = 0.0025). All three patients
      treated with cyclosporine A (CsA) were considered responders despite high serum
      ferritin and corticosteroid resistance. We also reviewed 93 patients with ALHS
      identified in 46 articles. Multiple logistic regression analysis identified C
      reactive protein (CRP) (OR 0.83, p = 0.042) and hemoglobin (OR 1.53, p = 0.026)
      measured at diagnosis of ALHS as significant predictors of the response to
      corticosteroid monotherapy. Moreover, among 32 patients treated with CsA, serum
      ferritin was significantly higher in CsA responders (12163 +/- 16864 ug/l, n =
      22) than in non-responders (3456 +/- 6267/ug/l, p = 0.020, n = 10). Leukocyte
      count was significantly lower in the CsA responders (1940.0 +/- 972.3/ul) than in
      the non-responders (3253 +/- 2198/ul, p = 0.034). CONCLUSION: Low CRP and high
      hemoglobin can predict a positive response to corticosteroid monotherapy while
      high serum ferritin and low leukocyte count can predict a positive response to
      CsA in patients with ALHS and therefore, when corticosteroid monotherapy is not
      effective in such cases, CsA could be the first choice of an additional
      immunosuppressive agent.

PMID- 25391545
TI  - Cloning and characterization of a multifunctional promoter from maize (Zea mays
      L.).
AB  - The use of tissue-specific promoters to drive the expression of target genes
      during certain developmental stages or in specific organs can prevent unnecessary
      gene expression caused by constitutive promoters. Utilizing heterologous
      promoters to regulate the expression of genes in transgenic receptors can help
      prevent gene silencing. Here, we engineered heterologous maize promoters that
      regulate gene-specific expression in rice plant receptors. We performed a
      histochemical and quantitative beta-glucuronidase (GUS) analysis of the Zea mays
      legumin1 (ZM-LEGF) gene promoter and detailed detection of stably transformed
      rice expressing the GUS gene under the control of the promoter of ZM-LEGF (pZM
      LEGF) and its truncated promoters throughout development. When the promoter
      sequence was truncated, the location and intensity of GUS expression changed. The
      results suggest that the sequence from -140 to +41 is a critical region that
      confers the expression of the entire promoter. Truncation of pZM-LEG (3'-deleted
      region of pZM-LEGF) markedly increased the GUS activity, with the core cis
      elements located in the -273 to -140 regions, namely pZM-LEG6. Detailed analysis
      of pZM-LEG6::GUS T2 transformant rice seeds and plant tissues at different
      developmental stages indicated that this promoter is an ideal vegetative tissue
      specific promoter that can serve as a valuable tool for transgenic rice breeding
      and genetic engineering studies. 

PMID- 25391546
TI  - Surface plasmon resonance based label-free detection of Salmonella using DNA self
      assembly.
AB  - Typhoid is re-emerging as a biggest health threat to third world countries. One
      of the major challenge is false negative diagnosis using existing
      immunodiagnostic methods due to overlapping symptoms of other infections (like
      brucellosis, malaria, hepatitis) that mimic this enteric fever (typhoid). Surface
      plasmon resonance (SPR) based DNA hybridisation biosensor has been fabricated by
      generating self-assembled monolayer of 5'-thiolated single-stranded DNA (ssDNA)
      probe onto gold surface. Highly specific DNA probe has been selected from
      conserved Vi capsular antigen gene of Salmonella enterica serovars typhi. This
      DNA biosensor has been investigated for label-free real-time monitoring of
      Salmonella. Interestingly, 0.019 ng mL(-1) (2 fM) is the lowest detected
      concentration in PBS with association (k a) and dissociation (k d) rate constants
      to be k a (M(-1) s(-1)) = 6.68 * 10(4) +/- 2.3 and k d (s(-1)) = 5.6 * 10(-3) +/-
      0.01, respectively. This biosensor was successfully demonstrated to distinguish
      complementary, non-complementary and one-base mismatch sequences and reusability
      up to 40 hybridisation cycles at room temperature. Successful results were
      obtained for hybridisation studies of genomic DNA isolated from spiked urine
      sample. Performance characteristics of this biosensing device suggested further
      scope to fine-tune such DNA-based assays to be implied for clinical, food and
      environmental applications.

PMID- 25391548
TI  - Perceptions of old age and aging in the continuing care retirement community.
AB  - BACKGROUND: The continuing care retirement community (CCRC) is a long term care
      alternative available to older adults who are independent upon entrance. The
      present study evaluated perceptions of old age and aging among new CCRC residents
      and their adult children. METHODS: A qualitative study with 34 dyads of older
      adults and their adult children (34 adult children and 36 older adults) was
      conducted. Interviews were analyzed using constant comparisons within and across
      interviews. Dyadic analysis of older adults-adult children interviews was
      followed. RESULTS: Three major themes concerning the perception of old age and
      aging emerged: (a) expectations for multiple losses that occur in old age; (b)
      different views and definitions of old age as being composed of various
      dimensions including chronological age, mental age, physical age and appearance
      and (c) diverse perceptions of the CCRC as a luxurious hotel vs. the "last stop."
      CONCLUSIONS: A more balanced portrayal of old age and the CCRC might result in an
      easier acceptance of these concepts among older adults and their adult children.

PMID- 25391547
TI  - Development of the designed ankyrin repeat protein (DARPin) G3 for HER2 molecular
      imaging.
AB  - PURPOSE: Human epidermal growth factor receptor-2 (HER2) overexpression is a
      predictor of response to anti-HER2 therapy in breast and gastric cancer.
      Currently, HER2 status is assessed by tumour biopsy, but this may not be
      representative of the larger tumour mass or other metastatic sites, risking
      misclassification and selection of suboptimal therapy. The designed ankyrin
      repeat protein (DARPin) G3 binds HER2 with high affinity at an epitope that does
      not overlap with trastuzumab and is biologically inert. We hypothesized that
      radiolabelled DARPin G3 would be capable of selectively imaging HER2-positive
      tumours, and aimed to identify a suitable format for clinical application.
      METHODS: G3 DARPins tagged with hexahistidine (His6) or with histidine glutamate
      (HE)3 and untagged G3 DARPins were manufactured using a GMP-compatible Pichia
      pastoris protocol and radiolabelled with (125)I, or with (111)In via DOTA linked
      to a C-terminal cysteine. BALB/c mice were injected with radiolabelled G3 and
      tissue biodistribution was evaluated by gamma counting. The lead construct ((HE)3
      G3) was assessed in mice bearing HER2-positive human breast tumour (BT474)
      xenografts. RESULTS: For both isotopes, (HE)3-G3 had significantly lower liver
      uptake than His6-G3 and untagged G3 counterparts in non-tumour-bearing mice, and
      there was no significantly different liver uptake between His6-G3 and untagged
      G3. (HE)3-G3 was taken forward for evaluation in mice bearing HER2-positive
      tumour xenografts. The results demonstrated that radioactivity from (111)In-(HE)3
      G3 was better maintained in tumours and cleared faster from serum than
      radioactivity from (125)I-(HE)3-G3, achieving superior tumour-to-blood ratios
      (343.7 +/- 161.3 vs. 22.0 +/- 11.3 at 24 h, respectively). On microSPECT/CT,
      (111)In-labelled and (125)I-labelled (HE)3-G3 could image HER2-positive tumours
      at 4 h after administration, but there was less normal tissue uptake of
      radioactivity with (111)In-(HE)3-G3. Preadministration of trastuzumab did not
      affect the uptake of (HE)3-G3 by HER2-positive tumours. CONCLUSION: Radiolabelled
      DARPin (HE)3-G3 is a versatile radioligand with potential to allow the
      acquisition of whole-body HER2 scans on the day of administration.

PMID- 25391549
TI  - Pharmacokinetics of hydrocodone extended-release tablets formulated with
      different levels of coating to achieve abuse deterrence compared with a
      hydrocodone immediate-release/acetaminophen tablet in healthy subjects.
AB  - BACKGROUND AND OBJECTIVE: A hydrocodone extended-release (ER) formulation
      employing the CIMA((r)) Abuse-Deterrence Technology platform was developed to
      provide resistance against rapid release of hydrocodone when tablets are
      comminuted or taken with alcohol. This study evaluated the pharmacokinetics of
      three hydrocodone ER tablet prototypes with varying levels of polymer coating to
      identify the prototype expected to have the greatest abuse deterrence potential
      based on pharmacokinetic characteristics that maintain systemic exposure to
      hydrocodone comparable to that of a commercially available hydrocodone immediate
      release (IR) product. METHODS: In this four-period crossover study, healthy
      subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg
      tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high
      level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP)
      10/325 mg every 6 h until four tablets were administered, with each of the four
      treatments administered once over the four study periods. Dosing periods were
      separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block
      opioid receptors. Blood samples for pharmacokinetic assessments were collected
      predose and through 72 h postdose. Parameters assessed included maximum observed
      plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area
      under the concentration-time curve from time 0 to infinity (AUC(0-infinity)).
      RESULTS: Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-,
      intermediate-, and high-level coating hydrocodone ER tablet prototypes,
      respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective
      median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to
      hydrocodone (AUC(0-infinity)) was comparable between hydrocodone ER tablet
      prototypes (640, 600, and 578 ng.h/mL, respectively) and hydrocodone IR/APAP (581
      ng.h/mL). No serious adverse events or deaths were reported. The most common
      adverse events included headache (26%) and nausea (18%). CONCLUSION: All three
      hydrocodone ER tablet prototypes (low-, intermediate-, and high-level polymer
      coating) demonstrated ER pharmacokinetic characteristics. The hydrocodone ER
      tablet prototype with the high-level coating was selected for development because
      of its comparable exposure to the hydrocodone IR/APAP formulation and potentially
      increased ability to resist rapid drug release upon product tampering because of
      a higher polymer coating level. All study medications were well tolerated in
      healthy naltrexone-blocked volunteers.

PMID- 25391551
TI  - Pork is UK's main source of hepatitis E infection, briefing hears.

PMID- 25391550
TI  - CYP3A4 polymorphism and lopinavir toxicity in an HIV-infected pregnant woman.
AB  - Cytochrome P450 (CYP) 3A4 has been considered to be the most important enzyme
      system for metabolism of lopinavir/ritonavir (LPV/r), a widely used HIV protease
      inhibitor (PI) recommended during pregnancy. Herein we present a clinical case of
      a pregnant HIV-infected woman who was taking standard doses of LPV/r, 400/100 mg
      twice daily. The trough plasma concentrations for LPV were fourfold above that
      recommended for PI-pretreated patients and toxicity associated with LPV/r and PI
      regimens was observed. These high concentrations continued after delivery in
      spite of a dosage reduction. The pharmacogenetic analysis revealed a genetic
      polymorphism in the CYP3A4 gene that encodes a non-functional protein. The
      pharmacokinetic study could indicate the occurrence of a phenomenon of non-linear
      pharmacokinetics which would justify why dosage reduction after pregnancy did not
      proportionally affect the patient's degree of exposure to the drug. In addition,
      an increment in CYP3A activity during pregnancy could explain lower LPV/r
      exposure during this period compared to postpartum, despite the impaired activity
      of CYP3A4 caused by the polymorphism.

PMID- 25391552
TI  - Evaluating the progress of the UK's Material Recycling Facilities: a mini review.
AB  - Over the last 15 years, the UK has made great strides in reducing the amount of
      waste being sent to landfill while also increasing the amount of waste being
      recycled. The key drivers for this change are the European Union Landfill
      Directive (1999/31/EC) and the UK Landfill Tax. However, also playing their part
      are the growing numbers of Material Recycling Facilities (MRFs), which process
      recyclables. This mini review evaluates the current state of MRFs in the UK,
      through extensive secondary research, and detailed primary data analysis
      focussing on MRFs located in South-East England, UK. This study also explores
      technologies that aim to generate energy from waste, including Waste-to-Energy
      (WtE) and Refuse-derived Fuel (RDF) facilities. These facilities can have a huge
      appetite for waste, which can be detrimental to recycling efforts as some of the
      waste being sent there should be recycled. It was found that the waste sent to a
      typical UK MRF would recycle around 92% of materials while 6% was sent to energy
      recovery and the remaining 2% ended up in landfill. Therefore, the total
      estimated rejected or non-compliance materials from MRFs are around 8%. A key
      recommendation from this study is to adopt a strategy to combine MRFs with a form
      of energy generation, such as WtE or RDF. This integrated approach would ensure
      any residual waste arising from the recycling process can be used as a
      sustainable fuel, while also increasing the recycling rates. 

PMID- 25391553
TI  - Assessment of heavy metals exposure, noise and thermal safety in the ambiance of
      a vacuum metallurgy separation system for recycling heavy metals from crushed e
      wastes.
AB  - Vacuum metallurgy separation (VMS) is a technically feasible method to recover
      Pb, Cd and other heavy metals from crushed e-wastes. To further determine the
      environmental impacts and safety of this method, heavy metals exposure, noise and
      thermal safety in the ambiance of a vacuum metallurgy separation system are
      evaluated in this article. The mass concentrations of total suspended particulate
      (TSP) and PM10 are 0.1503 and 0.0973 mg m(-3) near the facilities. The
      concentrations of Pb, Cd and Sn in TSP samples are 0.0104, 0.1283 and 0.0961 MUg
      m(-3), respectively. Health risk assessments show that the hazard index of Pb is
      3.25 * 10(-1) and that of Cd is 1.09 * 10(-1). Carcinogenic risk of Cd through
      inhalation is 1.08 * 10(-5). The values of the hazard index and risk indicate
      that Pb and Cd will not cause non-cancerous effects or carcinogenic risk on
      workers. The noise sources are mainly the mechanical vacuum pump and the water
      cooling pump. Both of them have the noise levels below 80 dB (A). The thermal
      safety assessment shows that the temperatures of the vacuum metallurgy separation
      system surface are all below 303 K after adopting the circulated water cooling
      and heat insulation measures. This study provides the environmental information
      of the vacuum metallurgy separation system, which is of assistance to promote the
      industrialisation of vacuum metallurgy separation for recovering heavy metals
      from e-wastes.

PMID- 25391554
TI  - A comparison of the different 3D CT scanning modes on the GTV delineation for the
      solitary pulmonary lesion.
AB  - OBJECTIVES: To investigate the impacts of the different three-dimensional CT
      (3DCT) scanning modes on the GTV delineation for solitary pulmonary lesion (SPL)
      based on four-dimensional CT (4DCT), and to evaluate the feasibility of using the
      spiral CT scan in CT simulation. MATERIALS AND METHODS: Twenty-one patients with
      SPL underwent axial CT scan, spiral CT scan and 4DCT simulation scan during free
      breathing, respectively. The same clinical radiation oncologist delineated the
      gross tumor volume (GTV) under the same CT window setting. GTVA and GTVS were
      created from the axial and spiral images, respectively. ITVMIP was created from
      the maximum intensity projection (MIP) reconstructed 4D images. The target
      volumes and position between GTVA, GTVS and ITVMIP were compared. The matching
      index (MI) between GTVA and GTVS, and the correlation between MI and GTVS were
      evaluated. RESULTS: ITVMIP was significantly larger than GTVA and GTVS (ps =
      0.000). The ratios of ITVMIP to GTVA and GTVS were 1.57 +/- 0.54 and 1.66 +/-
      0.61, respectively. There was no significant difference between GTVA and GTVS(p =
      0.16). A comparison of the centroidal positions in x, y, and z directions for
      GTVA, GTVS and GTV4Dmip showed no significant difference (px = 0.17, py = 0.40,
      pz = 0.48). Additionally, there was no difference between distances from the
      centroidal positions of GTVA and GTVS to the origin of coordinates (p = 0.51). MI
      between GTVA and GTVS was 0.41 +/- 0.24 (range 0-0.89), and it was positively
      correlated with the tumor volume (r = 0.64, p = 0.002). CONCLUSION: There was no
      impact on the volume or centroidal position of GTV by the axial scan or spiral
      scan in 3DCT simulation for SPL. MI between GTVA and GTVS was small. A positively
      correlation was found between MI and GTVS. Relative to axial scanning mode,
      spiral CT scan was more timesaving and more efficient, it was feasible in 3DCT
      simulation for SPL.

PMID- 25391555
TI  - Vulnerability of coastal livelihoods to shrimp farming: Insights from Mozambique.
AB  - Millions of people around the world depend on shrimp aquaculture for their
      livelihoods. Yet, the phenomenal growth of shrimp farming has often given rise to
      considerable environmental and social damage. This article examines the impacts
      of commercial, export-oriented shrimp aquaculture on local livelihood
      vulnerability by comparing the exposure, sensitivity, and adaptive capacity of
      shrimp farm employees with non-farm employees in rural Mozambique. Exposure to
      stressors was similar between the two groups. Shrimp farm employees had higher
      assets and higher adaptive capacity than non-farm employees. However, because
      their income is heavily dependent on a single commodity, shrimp farm employees
      were highly susceptible to the boom crop nature of intensive shrimp farming. The
      implications for aquaculture policy and vulnerability research are discussed. The
      article argues that coastal vulnerability is dynamic, variable, and influenced by
      multiple processes operating at multiple scales. 

PMID- 25391556
TI  - Satisfaction with fishing and the desire to leave.
AB  - Predicting who may leave a fishery is an important consideration when designing
      capacity reduction programs to enhance both ecological and economic
      sustainability. In this paper, the relationship between satisfaction and the
      desire to exit a fishery is examined for the Queensland East Coast Trawl fishery.
      Income from fishing, and changes in income over the last 5 years, were key
      factors affecting overall satisfaction. Relative income per se was not a
      significant factor, counter to most satisfaction studies. Continuing a family
      tradition of fishing and, for one group, pride in being a fisher was found to be
      significant. Satisfaction with fishing overall and the challenge of fishing were
      found to be the primary drivers of the desire to stay or leave the fishery.
      Surprisingly, public perceptions of fishing, trust in management and perceptions
      of equity in resource allocation did not significantly affect overall
      satisfaction or the desire to exit the fishery. 

PMID- 25391557
TI  - Natural Products in Cancer Prevention and Therapy, a selection of topics
      presented in the 2nd Edition PSE Symposium (Naples, Italy, 25th to 28th of June
      2013).

PMID- 25391558
TI  - Omega-3 fatty acid concentrate from Dunaliella salina possesses anti-inflammatory
      properties including blockade of NF-kappaB nuclear translocation.
AB  - The health benefits of omega-3 polyunsaturated fatty acids (omega-3 PUFA), mainly
      eicosapentaenoic acid (EPA 20:5) and docosahexaenoic acid (DHA, 22:6), have been
      long known. Although various studies have demonstrated the health benefits of
      omega-3 PUFA, the mechanisms of action of omega-3 PUFAs are still not completely
      understood. While the major commercial source is marine fish oil, in this study
      we suggest the marine micro algae, Dunaliella salina as an alternate source of
      omega-3 fatty acids. Treatment with this algal omega-3 fatty acid concentrate (Ds
      omega-3 FA) resulted in significant down-regulation of LPS-induced production of
      TNF-alpha and IL-6 by peripheral blood mononuclear cells (PBMCs). The concentrate
      was also found to be a potent blocker of cyclooxygenase (COX-2) and matrix
      metalloproteinase (MMP-2 and MMP-9) expression. The present study reveals the
      anti-inflammatory properties of Ds-omega-3 FA concentrate including the
      inhibition of NF-kappaB translocation.

PMID- 25391560
TI  - Letter from the Editor.

PMID- 25391559
TI  - Predicting risk of hospital and emergency department use for home care elderly
      persons through a secondary analysis of cross-national data.
AB  - BACKGROUND: Older adults remain the highest utilization group with unplanned
      visits to emergency departments and hospital admissions. Many have considered
      what leads to this high utilization and the answers provided have depended upon
      the independent measures available in the datasets used. This project was
      designed to further understanding of the reasons for older adult ED visits and
      admissions to acute care hospitals. METHODS: A secondary analysis of data from a
      cross-national sample of community residing elderly, 60 years of age or older,
      and most of whom received services from a local home-care program was conducted.
      The assessment instrument used in this study is the interRAI HC (home care),
      designed for use in assessing elderly home care recipients. The model
      specification stage of the study identified the baseline independent variables
      that do and do not predict the follow-up measure of hospitalization and ED use.
      Stepwise logistic regression was used next to identify characteristics that best
      identified elders who subsequently entered a hospital or visited an ED. The items
      generated from the final multivariate logistic equation using the interRAI home
      care measures comprise the interRAI Hospital-ED Risk Index. RESULTS: Independent
      measures in three key domains of clinical complications, disease diagnoses and
      specialized treatments were related to subsequent hospitalization or ED use.
      Among the eighteen clinical complication measures with higher, meaningful odds
      ratios are pneumonia, urinary tract infection, fever, chest pain, diarrhea,
      unintended weight loss, a variety of skin conditions, and subject self-reported
      poor health. Disease diagnoses with a meaningful relationship with hospital/ED
      use include coronary artery disease, congestive heart failure, cancer, emphysema
      and renal failure. Specialized treatments with the highest odds ratios were blood
      transfusion, IV infusion, wound treatment, radiation and dialysis. Two measures,
      Alzheimer's disease and day care appear to have a protective effect for
      hospitalization/ED use with lower odds ratios. CONCLUSIONS: Examination into
      "preventable" hospitalizations and re-hospitalizations for older adults who have
      the highest rates of utilization are occurring beneath an umbrella of assuring
      the highest quality of care and controlling costs. The interRAI Hospitalization
      ED Risk Index offers an effective approach to predicting hospitalization
      utilization among community dwelling older adults.

PMID- 25391561
TI  - Methods and techniques for measuring gas emissions from agricultural and animal
      feeding operations.
AB  - Emissions of gases from agricultural and animal feeding operations contribute to
      climate change, produce odors, degrade sensitive ecosystems, and pose a threat to
      public health. The complexity of processes and environmental variables affecting
      these emissions complicate accurate and reliable quantification of gas fluxes and
      production rates. Although a plethora of measurement technologies exist, each
      method has its limitations that exacerbate accurate quantification of gas fluxes.
      Despite a growing interest in gas emission measurements, only a few available
      technologies include real-time, continuous monitoring capabilities. Commonly
      applied state-of-the-art measurement frameworks and technologies were critically
      examined and discussed, and recommendations for future research to address real
      time monitoring requirements for forthcoming regulation and management needs are
      provided. 

PMID- 25391562
TI  - The second five years of sequential injection chromatography: significant
      developments in the technology and methodologies.
AB  - Sequential injection chromatography was proposed in 2003 to perform a simple,
      rapid, reagent-saving, environmentally benign, on-site, and instrumentally
      inexpensive separation procedure. Sequential injection chromatography is a
      version of sequential injection analysis, which is the second generation in the
      family of flow injection techniques. Despite its advantages over high-performance
      liquid chromatography, sequential injection chromatography has confronted some
      challenges. Furthermore, the applications of sequential injection chromatography
      in its first five years are almost all limited to pharmaceutical analysis.
      Interestingly, in its second five years, various developments in sequential
      injection chromatography technology were achieved. The developments have enhanced
      the efficiency of sequential injection chromatography and hence its applications
      have extended to biological, food, and environmental analyses. The main
      objectives of this review are to examine recent developments (2008-2013) in
      sequential injection chromatography and to describe how these developments
      improve the efficiency of the technology. The sequential injection chromatography
      methodologies reported during that period are also discussed along with
      controlling conditions and analytical results. The review also describes the
      principles, instrumentation, and procedure behind sequential injection
      chromatography. 

PMID- 25391563
TI  - Application of solid-phase extraction for trace elements in environmental and
      biological samples: a review.
AB  - The progress of novel sorbents and their function in preconcentration techniques
      for determination of trace elements is a topic of great importance. This review
      discusses numerous analytical approaches including the preparation and practice
      of unique modification of solid-phase materials. The performance and main
      features of ion-imprinting polymers, carbon nanotubes, biosorbents, and
      nanoparticles are described, covering the period 2007-2012. The perspective and
      future developments in the use of these materials are illustrated. 

PMID- 25391564
TI  - Recent advances in sample preparation methods for analysis of endocrine
      disruptors from various matrices.
AB  - Due to the high toxicity of endocrine disruptors (EDs), studies are being
      undertaken to design effective techniques for separation and detection of EDs in
      various matrices. Recently, research activities in this area have shown that a
      diverse range of chromatographic techniques are available for the quantification
      and analysis of EDs. Therefore, on the basis of significant, recent original
      publications, we aimed at providing an overview of different separation and
      detection methods for the determination of trace-level concentrations of selected
      EDs. The biological effects of EDs and current pretreatment techniques applied to
      EDs are also discussed. Various types of chromatographic techniques are presented
      for quantification, highlighting time- and cost-effective techniques that
      separate and quantify trace levels of multiple EDs from various environmental
      matrices. Reports related to methods for the quantification of EDs from various
      matrices primarily published since 2008 have been cited. 

PMID- 25391565
TI  - Biomedical investigations using Fourier transform-infrared microspectroscopy.
AB  - One of the most exciting recent developments in infrared spectroscopy has been
      the coupling of the spectrometer to an infrared microscope. The combination of
      the new infrared spectrometer and a microscope was a natural thought of
      scientists in these fields. This development has been so rewarding and so useful
      in solving today's chemical problems that infrared microspectroscopy has quickly
      become a significant subclassification of infrared spectroscopy. Infrared
      microspectroscopy has a much longer history than the recent enthusiasm would
      imply, however. The great interest in the use of infrared spectroscopy to solve
      biomedical problems that occurred in recent years shortly spread into the medical
      and biological fields. The aim of this review is to discuss the new developments
      in applications of FT-IR microspectroscopy in biomedical analysis, covering the
      period between 2008 and 2013. 

PMID- 25391566
TI  - The current state-of-the-art in the determination of pharmaceutical residues in
      environmental matrices using hyphenated techniques.
AB  - Several thousand tons of pharmaceuticals and their transformation products
      (metabolites and degradation products) are introduced into the environment each
      year. They affect both human health and the environment, therefore, analytical
      procedures enabling the determination of a wide range of pharmaceuticals at trace
      levels with minimal effort, time, and energy are required. Nowadays, hyphenated
      techniques are commonly applied in pharmaceutical analysis. This article provides
      a brief overview of the state-of-the-art and future trends in the determination
      of pharmaceutical residues and their transformation products with a focus on the
      most popular techniques in the field, such as ultra or high-performance liquid
      chromatography (UHPLC or HPLC) coupled with tandem mass spectrometry (MS/MS),
      quadrupole time-of-flight (QTOF), and a hybrid quadrupole/linear ion trap (QqLIT)
      in different environmental matrices (water, soil/sediment). Attention is paid to
      different aspects, benefits, and limitations of the application of UPLC and mass
      spectrometry-based techniques. 

PMID- 25391567
TI  - Positive and negative qualities of South African adolescents' parent and peer
      relationships.
AB  - Parent and peer relationships are important social resources for adolescents.
      South African research on adolescents' relationships, however, underemphasises
      these relationships as potential positive resources. Studies also tend to use
      samples from urban populations, while rural and semi-rural adolescent populations
      are neglected. This study focused on White and Coloured adolescents living in one
      South African semi-rural community and their ratings of positive and negative
      relationship qualities in relationships with parents and peers. Using the Network
      of Relationships Inventory (NRI), we found that mothers, best friends and
      romantic partners were relatively equal sources of social support. Mothers' high
      ratings for support, conflict and punishment may point to mothers bearing the
      primary responsibility for child care. Fathers' low support ratings raise concern
      as father involvement is important for adolescents' well-being. White
      participants overall rated their relationship higher for support and lower for
      negative qualities than the Coloured participants. 

PMID- 25391568
TI  - The phenomenon of adolescents placing pressure on their parents.
AB  - OBJECTIVE: Parents are under pressure from their adolescent children if they,
      contrary to their own convictions, are compelled to bend rules or adapt decisions
      to submit to the demands of their children. The objective of this investigation
      was to determine which factors contribute to this phenomenon. METHOD: The sample
      comprised 177 adolescents and their parents in the Mpumalanga province. Variables
      taken into account were individual factors (gender, age and personality of
      parents and adolescents); factors related to the family (family structure,
      working circumstances of parents, family relationships and birth order position
      of adolescents); developmental factors (identity formation of adolescents); and
      wider contextual factors (peer pressure during adolescence). RESULTS: From the
      parents' side factors such as self-concept, personality and parent-adolescent
      relationship explained almost 62% of the variance in the pressure that parents
      experience. Only one prominent adolescent factor could be identified, namely
      adolescent-parent relationship (seen from the adolescents' side). CONCLUSION: The
      results indicate that the pressure which parents encounter from their adolescent
      children is associated with parental variables rather than adolescent variables.
      Adolescents do not deliberately plan to place their parents under pressure, but
      factors on the parents' side create such a situation.

PMID- 25391569
TI  - Non-medical prescription opioid use and violent behaviour among adolescents.
AB  - OBJECTIVE: A pharmacological explanation for the observed positive association
      between opioid abuse and violence does not appear to exist. Several explanations
      have therefore been posited. This study attempted to shed additional light on the
      latent factors linking opioid abuse and adolescent violence. To the best of our
      knowledge, this is the first investigation to examine this relationship while
      distinguishing between adolescents who misused their own versus a diverted
      prescription. A secondary objective was to compare the estimated effects of
      opioid abuse to those of other substances. METHOD: The 2008 Washington State
      Healthy Youth Survey data were analysed. A full information maximum likelihood
      multiple regression was used to account for missing data. RESULTS: Diverted- and
      own-prescription opioid abuse among adolescents were evidenced to be relatively
      strong predictors of violent thoughts and subsequent violent behaviour.
      CONCLUSIONS: These findings, in conjunction with our unique operationalisation of
      violence, help us draw inferences about the true source of the relationship
      between opioid abuse and violence. The results also indicate that opioid abuse is
      a potentially modifiable risk factor for violence. The fact that this negative
      outcome was observed for youths abusing their own prescription is further cause
      for concern given the recent surge in opioid prescriptions.

PMID- 25391570
TI  - The search for a timely diagnosis: parents' experiences of their child being
      diagnosed with an Autistic Spectrum Disorder.
AB  - OBJECTIVE: This study aimed to describe the experiences of a group of South
      African parents whose children had received Autistic Spectrum Disorder (ASD)
      diagnoses. METHOD: A qualitative approach involving semi-structured interviews
      with a sample of eight parents (seven mothers and one father) of ASD children was
      used. RESULTS: These interviews highlighted key issues in the area of ASD in
      South Africa, including: a lack of knowledge amongst professionals, an
      unwillingness to diagnose, and lack of available support and facilities. Many of
      the parents in the sample reported significant difficulties in obtaining an ASD
      diagnosis. These findings are discussed in the light of the importance of early
      intervention in South Africa. CONCLUSIONS: Practitioners appear to be reluctant
      to diagnose and label children with ASD at an early age. This reluctance results
      in lost opportunities for early intervention and years of uncertainty and
      distress for families. Access to resources for diagnosis and intervention for
      children with ASD in South Africa appears to be limited to a few families. For
      this select population, many difficulties and much dissatisfaction with
      diagnostic processes remain. The study recommends enhancing awareness of ASD to
      facilitate early identification, and to strengthen the support offered to parents
      of children with ASD.

PMID- 25391571
TI  - The role of parental style in the conduct disorders: a comparison between
      adolescent boys with and without conduct disorder.
AB  - OBJECTIVE: An important contributing factor, but one that has not been
      investigated thoroughly in South Africa, is the role of parental styles which has
      been consistently found to be a precursor of conduct disorder. METHOD: To
      establish whether specific parental factors that contribute to this disorder in a
      South African sample, the Parental Bonding Instrument and the Family Environment
      Scale were administered to 2 groups of adolescent boys: a group diagnosed with
      conduct disorder (n = 40) and a group without a diagnosis of conduct disorder (n
      = 40). To test for significant differences between the two groups, t-tests were
      performed. RESULTS: A typical parenting style characterised by low care by the
      mother and overprotection by the father, which forms an affectionless,
      controlling parenting style, was found in the children in the conduct disorder
      group. This type of parenting style results in high control, low expressiveness
      of emotions, minimal involvement with children, and inadequate supervision and
      monitoring of children. CONCLUSION: The study provided sufficient evidence to
      conclude that a specific style of parenting can contribute to the aetiology of
      conduct disorder.

PMID- 25391572
TI  - Correlates of inconsistent condom use among youth aged 18-24 years in South
      Africa.
AB  - This paper examines the correlates of inconsistent condom use with most recent
      sexual partner among sexually experienced youth (N = 2 138) in South Africa. A
      cross-sectional population based survey with youth aged 18 to 24 years was
      conducted in 4 provinces (Eastern Cape, Gauteng, KwaZulu-Natal and Mpumalanga).
      More women than men (57.7% vs. 25.8%) reported inconsistent condom use with their
      most recent partner. Multivariate analysis indicated that for males, not having
      talked with a partner about condoms in the past 12 months, having 2 or more
      sexual partners in the past 12 months, having ever had a transactional sex
      partner and alcohol use before sex in the past 3 months were associated with
      inconsistent condom use with their most recent sexual partner. In females
      multivariate analysis showed that lack of self-efficacy, not having talked with a
      partner about condoms in the past 12 months, having ever had or been subjected to
      forced sex and hazardous or harmful alcohol use were found to be associated with
      inconsistent condom use with their most recent sexual partner in multivariate
      analysis. 

PMID- 25391573
TI  - 'Recovery': does it fit for adolescent mental health?
AB  - The notion of 'recovery' in mental health has a long and diverse history in terms
      of definition, treatment processes and outcomes. Particularly with regard to
      definition, there has been much debate in the literature. The aim of this paper
      is to extend the discussion by exploring how the concept is used for two
      developmentally divergent populations--adults and adolescents. I argued that it
      is indeed appropriate and valid to use 'recovery' in the treatment process for
      adolescents. However, while adults share various facets of the recovery process
      with their adolescent counterparts, there are also significant differences such
      as physiological change, the impact of peers, identity development and the role
      of family. These crucial differences must guide any clinical services for the
      adolescent population.

PMID- 25391576
TI  - Pitfall in cannabinoid analysis--detection of a previously unrecognized
      interfering compound in human serum.
AB  - In clinical and forensic toxicology, high-performance liquid
      chromatography/tandem mass spectrometry (LC-MS/MS) is increasingly used since it
      allows the development of sensitive and fast drug analysis procedures. During
      development of a LC-MS/MS method for determination of the psychoactive
      cannabinoid Delta(9)-tetrahydrocannabinol (THC) and of its two metabolites 11
      hydroxy-THC (THCOH) and 11-nor-9-carboxy-THC (THCCOOH) in serum, a previously
      unrecognized interfering compound was detected. Extending the fast gradient
      elution program by an isocratic phase leads to sufficient separation of the
      interfering compound, initially co-eluting with THCCOOH and exhibiting the same
      fragments. For characterization, product ion scans and precursor ion scans were
      performed. Samples from cannabis users were analyzed to estimate the abundance of
      the interfering compound. The mass spectrometric experiments showed that the
      interfering compound exhibited the same molecular mass as THCCOOH and a similar
      fragmentation pattern except for relative fragment intensities. This compound was
      exclusively detectable in authentic samples. Concentrations were in the range of
      4.5 to 51 % (median 14.6 %, n = 73) of those of THCCOOH. After further
      optimization of the gradient, the method was sufficiently selective and sensitive
      and validation parameters were within acceptance limits. A new compound related
      to cannabis use was detected in human serum, and data suggest an isomeric
      structure to THCCOOH. Considering the rather high amounts observed, it was
      surprising that this compound had not been detected previously. Further studies
      on its structure and origin are necessary. 

PMID- 25391579
TI  - Erratum to: Metabolic response to 36 hours of fasting in young men born small vs
      appropriate for gestational age.

PMID- 25391580
TI  - Efficacy and safety of angiotensin receptor blockers in older patients: a meta
      analysis of randomized trials.
AB  - BACKGROUND: The efficacy and safety of angiotensin receptor blockers (ARBs) in
      the older population is unclear. OBJECTIVES: To determine the efficacy and safety
      of ARBs in older patients. METHODS: Randomized trials that compared ARBs to
      control and reported clinical outcomes in patients with a mean age of 65 years or
      older were included. Random-effects summary risk ratios (RRs) were constructed.
      RESULTS: A total of 16 trials met our selection criteria, which yielded 113,386
      patients. ARBs were associated with a marginal increased risk of all-cause
      mortality (RR: 1.03, 95% confidence interval (CI): 1.00-1.06, P = 0.05), a
      nonsignificant increased risk of myocardial infarction (RR: 1.04, 95% CI: 0.96
      1.12, P = 0.36), a marginal reduction in heart failure hospitalization (RR: 0.86,
      95% CI: 0.74-1.00, P = 0.06), and a significant reduction in the risk of stroke
      (RR: 0.93, 95% CI: 0.87-0.99, P = 0.03). ARBs were associated with an increased
      risk of acute kidney injury (RR: 1.48, 95% CI: 1.24-1.77, P < 0.001), hypotension
      (RR: 1.56, 95% CI: 1.24-1.97, P < 0.001), and hyperkalemia (RR: 1.57, 95% CI:
      1.13-2.19, P = 0.008). On the sensitivity analysis including placebo-controlled
      trials, the risk of all-cause mortality was no longer significant (P = 0.2),
      while the remainder of the outcomes did not change. CONCLUSION: In older
      patients, the benefit of ARBs compared with control was strongest for stroke
      reduction, with no (or weak) associations for all-cause mortality, myocardial
      infarction, and heart failure hospitalization. Benefit was offset by an increased
      risk of acute kidney injury, hypotension, and hyperkalemia. Thus, ARBs should be
      used with caution in older patients when clinically indicated.

PMID- 25391581
TI  - Preface to special issue on current topics in photochemistry.

PMID- 25391582
TI  - Preventing occupational stress in healthcare workers.
AB  - Background Healthcare workers can suffer from occupational stress as a result of
      lack of skills, organisational factors, and low social support at work.which may
      lead to distress, burnout and psychosomatic problems, and deterioration in
      quality of life and service provision.Objectives To evaluate the effectiveness of
      work- and person-directed interventions compared to no intervention or
      alternative interventions in preventing stress at work in healthcare
      workers.Search methods We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL,NIOSHTIC-2 and Web of Science
      up to November 2013.Selection criteria Randomised controlled trials (RCTs) of
      interventions aimed at preventing psychological stress in healthcare workers. For
      organisational interventions, interrupted time-series and controlled before-and
      after (CBA) studies were also eligible.Data collection and analysis Two review
      authors independently extracted data and assessed trial quality. We used
      Standardised Mean Differences (SMDs) where authors of trials used different
      scales to measure stress or burnout. We combined studies that were similar in
      meta-analyses. We used the GRADE system to rate the quality of the evidence.Main
      results In this update, we added 39 studies, making a total of 58 studies (54
      RCTs and four CBA studies), with 7188 participants. We categorised interventions
      as cognitive-behavioural training (CBT) (n = 14), mental and physical relaxation
      (n = 21), combined CBT and relaxation (n = 6) and organisational interventions (n
      = 20). Follow-up was less than one month in 24 studies, one to six in 22 studies
      and more than six months in 12 studies. We categorised outcomes as stress,
      anxiety or general health. There was low-quality evidence that CBT with or
      without relaxation was no more effective in reducing stress symptoms than no
      intervention at one month follow-up in six studies (SMD -0.27 (95% Confidence
      Interval (CI) -0.66 to 0.13; 332 participants). But at one to six months follow
      up in seven studies (SMD -0.38, 95% CI -0.59 to -0.16; 549 participants, 13%
      relative risk reduction),and at more than six months follow-up in two studies
      (SMD -1.04, 95% CI -1.37 to -0.70; 157 participants) CBT with or without
      relaxation reduced stress more than no intervention.CBT interventions did not
      lead to a considerably greater effect than an alternative intervention, in three
      studies.Physical relaxation (e.g. massage) was more effective in reducing stress
      than no intervention at one month follow-up in four studies(SMD -0.48, 95% CI 
      0.89 to -0.08; 97 participants) and at one to six months follow-up in six studies
      (SMD -0.47; 95% CI -0.70 to-0.24; 316 participants). Two studies did not find a
      considerable difference in stress between massage and taking extra breaks.Mental
      relaxation (e.g. meditation) led to similar stress symptom levels as no
      intervention at one to six months follow-up in six studies(SMD -0.50, 95% CI 
      1.15 to 0.15; 205 participants) but to less stress in one study at more than six
      months follow-up. One study showed that mental relaxation reduced stress more
      effectively than attending a course on theory analysis and another that it was
      more effective than just relaxing in a chair.Organisational interventions
      consisted of changes in working conditions, organising support, changing care,
      increasing communication skills and changing work schedules. Changing work
      schedules (from continuous to having weekend breaks and from a four-week to a two
      week schedule) reduced stress with SMD -0.55 (95% CI -0.84 to -0.25; 2 trials,
      180 participants). Other organisational interventions were not more effective
      than no intervention or an alternative intervention.We graded the quality of the
      evidence for all but one comparison as low. For CBT this was due to the
      possibility of publication bias,and for the other comparisons to a lack of
      precision and risk of bias. Only for relaxation versus no intervention was the
      evidence of moderate quality.Authors' conclusions There is low-quality evidence
      that CBT and mental and physical relaxation reduce stress more than no
      intervention but not more than alternative interventions. There is also low
      quality evidence that changing work schedules may lead to a reduction of stress.
      Other organisational interventions have no effect on stress levels.More
      randomised controlled trials are needed with at least 120 participants that
      compare the intervention to a placebo-like intervention. Organisational
      interventions need better focus on reduction of specific stressors.

PMID- 25391583
TI  - Associations of Sexual Subjectivity with Global and Sexual Well-Being: A New
      Measure for Young Males and Comparison to Females.
AB  - Sexual subjectivity refers to multiple aspects of sexual self-perceptions,
      including sexual body-esteem, perceptions of efficacy and entitlement to sexual
      desire and pleasure, and sexual self-reflection (Horne & Zimmer-Gembeck, 2006).
      Previous research on sexual subjectivity has shown that it is elevated in young
      women who report better global well-being and have more sexual experience.
      However, research has not focused on young men. Thus, two studies were conducted
      to develop a new measure to assess young men's sexual subjectivity (Study 1, N =
      304 men) and to examine associations of sexual subjectivity with general and
      sexual well-being among young men and women (Study 2, N = 208 men and 214 women).
      In Study 1, five elements of men's sexual subjectivity were found, which
      paralleled the elements found in previous research with young women. In Study 2,
      sexual subjectivity, especially two elements of sexual body-esteem and self
      efficacy in achieving pleasure, was significantly associated with enhanced global
      and sexual well-being in both men and women. Gender did not moderate these
      associations, supporting sexual subjectivity as an aspect of sexual health in all
      young adults. As anticipated, men reported greater entitlement to self-pleasure
      and self-efficacy in achieving pleasure, but women reported greater entitlement
      to pleasure with partners. Women's feelings of less efficacy but more entitlement
      to pleasure with partners suggest that feelings of entitlement may not be
      consistent with their experiences. Future research with young men and women will
      be important for understanding sexual health and development during late
      adolescence and early adulthood.

PMID- 25391584
TI  - Self-reported sex partner dates for use in measuring concurrent sexual
      partnerships: correspondence between two assessment methods.
AB  - Although prevalence of concurrent sexual partnerships is increasingly
      investigated as a driver of HIV epidemics, its measurement varies and its role in
      transmission dynamics remains contested. Relying on different methods of
      obtaining self-reported partnership histories may lead to significant differences
      in prevalence. This study examined the reliability of two methods for assessing
      dates of sex and the implications for measuring concurrent sexual partnerships.
      We conducted a cross-sectional reliability study using self-reported survey data
      from 650 women ages 18-65 years, recruited online nationwide for human
      papillomavirus natural history studies from 2007 to 2012. Intermethod reliability
      of first and last sex with the most recent partner was assessed using weighted
      kappa. Intraclass correlation coefficient was estimated for intramethod
      reliability across two consecutive questionnaires administered 4 months apart.
      Point prevalence of concurrent sexual partnerships at 6 months prior to the
      questionnaire date was similar between the two question formats (10.5 % for
      categorical and 10.9 % for continuous). The range between the minimum and maximum
      cumulative prevalence for 12 months was larger when using the categorical
      questions (17.0-29.6 % compared to 27.6-28.6 % using the continuous questions).
      Agreement between the two question formats was moderate for the date of first sex
      with the most recent partner (kappa = 0.56, 95 % CI 0.48-0.64) and almost perfect
      for the date of last sex (kappa = 0.93, 95 % CI 0.91-0.94). Longitudinal
      agreement for date of first sex was high for the continuous date question (ICC =
      0.89, 95 % CI 0.86-0.92). Results of this reliability study can be used to inform
      the design of future studies of concurrent sexual partnerships and their
      association with HIV.

PMID- 25391585
TI  - Sexual feelings toward the therapist among patients with borderline personality
      disorder: a case of erotomanic delusional disorder.

PMID- 25391586
TI  - Same data, different perspectives: what is at stake? Response to Savin-Williams
      and Joyner (2014a).

PMID- 25391588
TI  - You are at the heart of patient safety.

PMID- 25391587
TI  - Changes in CEBPB expression in circulating leukocytes following eccentric elbow
      flexion exercise.
AB  - In mouse models, CCAAT enhancer-binding protein beta (CEBPB) is necessary for M2
      macrophage-mediated regeneration after muscle injury. In humans, CEBPB expression
      in blood was strongly associated with muscle strength. In this study we aimed to
      test whether CEBPB expression in blood in people is increased 2 days after
      exercise designed to induce muscle damage and subsequent repair. Sixteen healthy
      male volunteers undertook elbow flexor exercises designed to induce acute muscle
      micro-damage. Peripheral blood samples were collected at baseline and days 1, 2,
      4 and 7 following exercise. Expression of CEBPB and related genes were analysed
      by qRT-PCR. Extent of muscle damage was determined by decline in maximal
      voluntary isometric torque and by plasma creatine kinase activity. Nine subjects
      had peak (day 4) creatine kinase activity exceeding 10,000 U/l. In this subgroup,
      CEBPB expression was elevated from baseline to 2 days post exercise (paired
      samples t (1,8) = 3.72, p = 0.006). Related expression and selected cytokine
      changes after exercise did not reach significance. Muscle-damaging exercise in
      humans can be followed by induction of CEBPB transcript expression in peripheral
      blood. Associations between CEBPB expression in blood and muscle strength may be
      consistent with the CEBPB-dependent muscle repair process.

PMID- 25391589
TI  - Supporting women with substance use issues: trauma-informed care as a foundation
      for practice in the NICU.
AB  - Infants with neonatal abstinence syndrome and their mothers require extended
      support through health and social service systems. Practitioners are interested
      in exploring innovative approaches to caring for infants and mothers. There is
      now compelling evidence linking women's substance use to experiences of trauma
      and violence. A significant shift in the fields of addiction and mental health
      has been awareness of the impact of trauma and violence on infants and children,
      women, their families, and communities. In this article, the current state of
      knowledge of trauma-informed care is reviewed, in particular for application to
      practice within the NICU. Trauma survivors are at risk of being retraumatized
      because of health care providers' limited understanding of how to work
      effectively with them. Recognizing the impact of trauma and implementing evidence
      based trauma-informed practices in the NICU holds promise for improving outcomes
      for women and their infants. 

PMID- 25391590
TI  - Neonatal liver cell donation: a case report.
AB  - Traditional organ transplant options for newborns have been rare. There continues
      to be an increasing need for organs for transplant and a limited number of
      available organs, especially for small children. Liver cell transplantation is a
      promising alternative to orthotopic liver transplantation to treat liver-based
      inborn errors of metabolism.1 The procedure is minimally invasive and can be
      performed repeatedly. The safety of the procedure has been well established, and
      the clinical results are encouraging.1 The liver cell donation process is an
      option for families who experience the loss of a newborn and offers them a legacy
      for their child by providing life for others. The purpose of this article is to
      discuss the neonatal liver cell donation process and present a case report of an
      anencephalic infant whose parents chose to participate in this unique program. 

PMID- 25391591
TI  - Validity and reliability of breastfeeding advice and coping with breastfeeding
      instruments.
AB  - PURPOSE: To pilot two instruments: Breastfeeding Advice and Coping with
      Breastfeeding in NICU settings. DESIGN: Psychometric testing of the Breastfeeding
      Advice and Coping with Breastfeeding instruments. SAMPLE: Mothers (N = 47) with
      singleton or twin preterm (<=36 + 6 gestation weeks) infant(s) (N = 55) at
      discharge collected from seven NICUs in Finland. MAIN OUTCOME VARIABLES: The
      validity and reliability of two instruments: Breastfeeding Advice measuring the
      quality of breastfeeding counseling and Coping with Breastfeeding measuring the
      mothers' experienced ability to cope with breastfeeding issues. RESULTS: Infants'
      mean gestation age was 32.5 weeks at birth. The items of the instruments were
      supported by previous studies, demonstrating content validity. There was a
      significant correlation (r = .72, p < .001) between Breastfeeding Advice and
      Coping with Breastfeeding, indicating constructor validity. Evidence for
      predictive validity was not found. Good reliability for internal consistency of
      the Breastfeeding Advice (Cronbach's alpha = .86) and Coping with Breastfeeding
      (Cronbach's alpha = .85) was found.

PMID- 25391592
TI  - Pyloric atresia in the neonate.
AB  - Bowel obstruction is a common cause for admission into the NICU, but pyloric
      atresia (PA) is a very rare cause of bowel obstruction. This article illustrates
      the development of the fetal gastrointestinal tract, most specifically the
      stomach and pylorus. Pathophysiology, typing, and treatment of PA are also
      explored. Presented are two cases of PA that occurred in a Level III NICU one
      month apart. Management of this condition is surgical in nature. Long-term
      prognosis is usually excellent because this defect is often isolated. 

PMID- 25391593
TI  - Pain in the neonate: focus on nonpharmacologic interventions.
AB  - The assessment and treatment of pain in the neonate, especially preterm neonates,
      has been a challenge in the NICU for many years. Nurses caring for these
      vulnerable patients are in a key position to not only recognize when the neonate
      is experiencing pain but to also work collaboratively with other health care
      providers in determining the best method to treat and help prevent pain
      associated with procedures and routine caregiving activities. The American
      Academy of Pediatrics along with parent groups has recognized the importance of
      pain-prevention programs in treating pain in the neonate. Nurses, by anticipating
      and reducing both painful procedures and bedside interruptions, along with
      innovative nonpharmacologic interventions, can dramatically decrease the
      neonate's exposure to pain and the potential for long-term effects. An overview
      of nonpharmacologic interventions in the treatment of neonatal pain is provided
      for NICU nurses to help them effectively reduce their patient's pain and
      discomfort. 

PMID- 25391594
TI  - Central venous catheter-induced pericardial effusion in a neonate: a case study
      and recommendations for practice.
AB  - Pericardial effusion (PCE) and tamponade as a complication of central venous
      catheters (CVCs) continues to occur in the neonatal population. It is imperative
      that clinicians managing neonates with CVCs practice vigilance regarding proper
      catheter tip location. Furthermore, it is of equal importance that clinicians
      have a high index of suspicion regarding the catheter tip location any time a
      neonate with a CVC has a clinical deterioration. It is clear that the ultimate
      outcome of PCE depends on rapid identifi cation and a quick response when
      pericardial tamponade occurs. PCE can occur any time during the duration of the
      catheter dwell time, and education of staff caring for neonates will assist in
      prevention and rapid treatment. 

PMID- 25391596
TI  - An evidence-based safe sleep teaching program.
AB  - This column describes the experience of the units practice council in developing
      an evidence-based practice teaching program focused on safe sleep for newborn
      infants. 

PMID- 25391597
TI  - Drug-exposed newborns and caregivers:quality care collaborative for the mother
      baby-community triad.

PMID- 25391600
TI  - Impact of kangaroo mother care on cerebral blood flow of preterm infants.
AB  - BACKGROUND: Kangaroo mother care (KMC) has been widely used to improve the care
      of preterms and low birth weight infants. However, very little is known about
      cerebral hemodynamics responses in preterm infants during KMC intervention. The
      aim of this study is to evaluate the changes of cerebral blood flow (CBF) in
      middle cerebral artery, before and after a 30 minute application of KMC in stable
      preterm infants. METHODS: It is a prospective, pre-post test without a control
      group study. CBF flow paremeters were measured with Doppler ultrasonography in
      one middle cerebral artery. Sixty preterm stable infants were assessed before and
      after 30 min KMC. CBF indices were assessed in different positions before KMC,
      forty neonates in supine position and 20 in vertical suspension (baby is held
      vertically away from the skin of his mother). Other dependent variables heart
      rate and mean arterial blood pressure and Spo2 were also studied before and after
      KMC. RESULTS: The mean gestational age of the infants was (32 +/- 2 weeks), and
      mean birth weight was (2080 +/- 270 gm). Comparing CBF indices (Pulsatility index
      and Resistive index) before and after KMC has shown a significant decrease in
      both Pulsatility index (PI) and Resistive index (RI) after 30 min. KMC, the mean
      values were (2.0 +/- 0.43 vs 1.68 +/- 0.33 & 0.81 +/- 0.05 vs 0.76 +/- 0.06
      respectively P < 0.05*) with mean difference (0.32 & 95% CI 0.042-0.41 & 0.05 &
      95% CI 0.04 to 0.06 respectively P < 0.05*) and increase in end diastolic
      velocity & mean velocity 30 min of KMC (10.97 +/- 4.63 vs. 15.39 +/- 5.66 P <
      0.05*& 25.66 +/- 10.74 vs. 32.86 +/- 11.47 P < 0.05* ) with mean difference (-
      4.42 & 95% CI -5.67 to -3.18 and -7.21 & 95% CI - 9.41 to 5.00 respectively).
      These changes indicate improvement in CBF. No correlation has been found between
      CBF parameters and studied vital signs or SpO2. CONCLUSION: Kangaroo mother care
      improves cerebral blood flow, thus it might influence the structure and promote
      development of the premature infant's brain.

PMID- 25391599
TI  - Monitoring CO2 in shock states.
AB  - The primary end point when treating acute shock is to restore blood circulation,
      mainly by reaching macrocirculatory parameters. However, even if global
      haemodynamic goals can be achieved, microcirculatory perfusion may remain
      impaired, leading to cellular hypoxia and organ damage. Interestingly, few
      methods are currently available to measure the adequacy of organ blood flow and
      tissue oxygenation. The rise in tissue partial pressure of carbon dioxide (CO2)
      has been observed when tissue perfusion is decreased. In this regard, tissue
      partial pressure of CO2 has been proposed as an early and reliable marker of
      tissue hypoxia even if the mechanisms of tissue partial pressure in CO2 rise
      during hypoperfusion remain unclear. Several technologies allow the estimation of
      CO2 content from different body sites: vascular, tissular (in hollow organs,
      mucosal or cutaneous), and airway. These tools remain poorly evaluated, and some
      are used but are not widely used in clinical practice. The present review
      clarifies the physiology of increasing tissue CO2 during hypoperfusion and
      underlines the specificities of the different technologies that allow bedside
      estimation of tissue CO2 content. 

PMID- 25391602
TI  - Going against medical advice: PCPs' role in reducing colonoscopy overuse.

PMID- 25391601
TI  - Effectiveness of a physical activity and weight loss intervention for middle-aged
      women: healthy bodies, healthy hearts randomized trial.
AB  - BACKGROUND: Physical inactivity is a significant risk factor for cardiovascular
      disease and remains highly prevalent in middle-aged women. OBJECTIVE: We
      hypothesized that an interventionist-led (IL), primary-care-based physical
      activity (PA) and weight loss intervention would increase PA levels and decrease
      weight to a greater degree than a self-guided (SG) program. DESIGN: We conducted
      a randomized trial. PARTICIPANTS: Ninety-nine inactive women aged 45-65 years and
      with BMI >= 25 kg/m(2) were recruited from three primary care clinics.
      INTERVENTIONS: The interventionist-led (IL) group (n = 49) had 12 weekly sessions
      of 30 min discussions with 30 min of moderate-intensity PA. The self-guided (SG)
      group (n = 50) received a manual for independent use. MAIN MEASURES: Assessments
      were conducted at 0, 3, and 12 months; PA and weight were primary outcomes.
      Weight was measured with a standardized protocol. Leisure PA levels were assessed
      using the Modifiable Activity Questionnaire. Differences in changes by group were
      analyzed with a t-test or Wilcoxon rank-sum test. Mixed models were used to
      analyze differences in changes of outcomes by group, using an intention-to-treat
      principle. KEY RESULTS: Data from 98 women were available for analysis. At
      baseline, mean (SD) age was 53.9 (5.4) years and 37 % were black. Mean weight was
      92.3 (17.7) kg and mean BMI was 34.7 (5.9) kg/m(2). Median PA level was 2.8
      metabolic equivalent hours per week (MET-hour/week) (IQR 0.0, 12.0). At 3 months,
      IL women had a significantly greater increase in PA levels (7.5 vs. 1.9 MET
      hour/week; p = 0.02) than SG women; there was no significant difference in weight
      change. At 12 months, the difference between groups was no longer significant
      (4.7 vs. 0.7 MET-hour/week; p = 0.38). Mixed model analysis showed a significant
      (p = 0.048) difference in PA change between groups at 3 months only. CONCLUSIONS:
      The IL intervention was successful in increasing the physical activity levels of
      obese, inactive middle-aged women in the short-term. No significant changes in
      weight were observed.

PMID- 25391603
TI  - Radio frequency radiation-induced hyperthermia using Si nanoparticle-based
      sensitizers for mild cancer therapy.
AB  - Offering mild, non-invasive and deep cancer therapy modality, radio frequency
      (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF
      sensitizers to selectively target cancer cells and thus avoid side effects. Here,
      we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF
      induced therapy. Using nanoparticles produced by mechanical grinding of porous
      silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced
      heating of aqueous suspensions of the nanoparticles to temperatures above 45-50 
      degrees C under relatively low nanoparticle concentrations (<1 mg/mL) and RF
      radiation intensities (1-5 W/cm(2)). For both types of nanoparticles the heating
      rate was linearly dependent on nanoparticle concentration, while laser-ablated
      nanoparticles demonstrated a remarkably higher heating rate than porous silicon
      based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL.
      The observed effect is explained by the Joule heating due to the generation of
      electrical currents at the nanoparticle/water interface. Profiting from the
      nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis
      lung carcinoma in vivo. Combined with the possibility of involvement of parallel
      imaging and treatment channels based on unique optical properties of Si-based
      nanomaterials, the proposed method promises a new landmark in the development of
      new modalities for mild cancer therapy.

PMID- 25391604
TI  - Investigation of genetic factors underlying typical orofacial clefts: mutational
      screening and copy number variation.
AB  - Typical orofacial clefts (OFCs) comprise cleft lip, cleft palate and cleft lip
      and palate. The complex etiology has been postulated to involve chromosome
      rearrangements, gene mutations and environmental factors. A group of genes
      including IRF6, FOXE1, GLI2, MSX2, SKI, SATB2, MSX1 and FGF has been implicated
      in the etiology of OFCs. Recently, the role of the copy number variations (CNVs)
      has been studied in genetic defects and diseases. CNVs act by modifying gene
      expression, disrupting gene sequence or altering gene dosage. The aims of this
      study were to screen the above-mentioned genes and to investigate CNVs in
      patients with OFCs. The sample was composed of 23 unrelated individuals who were
      grouped according to phenotype (associated with other anomalies or isolated) and
      familial recurrence. New sequence variants in GLI2, MSX1 and FGF8 were detected
      in patients, but not in their parents, as well as in 200 control chromosomes,
      indicating that these were rare variants. CNV screening identified new genes that
      can influence OFC pathogenesis, particularly highlighting TCEB3 and KIF7, that
      could be further analyzed. The findings of the present study suggest that the
      mechanism underlying CNV associated with sequence variants may play a role in the
      etiology of OFC. 

PMID- 25391605
TI  - Association of neonatal hyperbilirubinemia in breast-fed infants with UGT1A1 or
      SLCOs polymorphisms.
AB  - Neonates have physiologically increased bilirubin production and immature
      bilirubin metabolism, and present hyperbilirubinemia in association with genetic
      and or epigenetic factors. We previously reported that maximal body weight loss
      (inadequate feeding) is an independent risk factor for the development of
      hyperbilirubinemia in breast-fed Japanese neonates, and the UGT1A1 211G>A
      genotype becomes a risk factor under conditions of inadequate feeding. We
      extended the study to the association of other genetic factors, the UGT1A1 (TA)7
      and solute-carrier organic anion transporters (SLCOs) polymorphisms with neonatal
      hyperbilirubinemia. We enrolled 401 full-term Japanese infants who were
      exclusively breastfeeding and classified them into two groups based on the degree
      of maximal body weight loss. We analyzed the clinical characteristics and UGT1A1
      and SLCOs genotypes. Statistical analysis revealed that maximal body weight loss
      is the only independent risk factor for the development of neonatal
      hyperbilirubinemia. UGT1A1, SLCO1B1 and SLCO1B3 polymorphisms become risk factors
      in neonates showing 10% or greater body weight loss during the neonatal period.
      Inadequate feeding may increase the bilirubin burden and cause apparent
      hyperbilirubinemia in neonates, who have a polymorphic change in the genes
      involved in the transport and/or metabolism of bilirubin. 

PMID- 25391606
TI  - Identification of two novel mutations in the NOG gene associated with congenital
      stapes ankylosis and symphalangism.
AB  - In this study, we describe three unrelated Japanese patients with hearing loss
      and symphalangism who were diagnosed with proximal symphalangism (SYM1), atypical
      multiple synostosis syndrome (atypical SYNS1) and stapes ankylosis with broad
      thumb and toes (SABTT), respectively, based on the clinical features. Surgical
      findings in the middle ear were similar among the patients. By next-generation
      and Sanger sequencing analyses, we identified two novel mutations, c.559C>G
      (p.P178A) and c.682T>A (p.C228S), in the SYM1 and atypical SYNS1 families,
      respectively. No pathogenic changes were found in the protein-coding regions,
      exon-intron boundaries or promoter regions of the NOG, GDF5 or FGF9 genes in the
      SABTT family. Such negative molecular data suggest there may be further genetic
      heterogeneity underlying SYNS1, with the involvement of at least one additional
      gene. Stapedotomy resulted in good hearing in all patients over the long term,
      indicating no correlation between genotype and surgical outcome. Given the
      overlap of the clinical features of these syndromes in our patients and the
      molecular findings, the diagnostic term 'NOG-related-symphalangism spectrum
      disorder (NOG-SSD)' is advocated and an unidentified gene may be responsible for
      this disorder. 

PMID- 25391607
TI  - EELS study of Fe- or Co-doped titania nanosheets.
AB  - Ti0.6Fe0.4O2 and Ti0.8Co0.2O2 nanosheets are Fe- and Co-doped titanium oxides,
      respectively, and they are synthesized by the exfoliation of lepidocrocite-type
      layered titanates. We have investigated these nanosheets by electron energy-loss
      spectroscopy (EELS) using a monochromated transmission electron microscope. The
      energy-loss near-edge structures (ELNESs) of Fe-L and Co-L indicate that Fe(3+)
      and Co(2+) ions are substituted in the octahedral sites in each nanosheet. The Ti
      L edges of Ti0.6Fe0.4O2 and Ti0.8Co0.2O2 nanosheets correspond to the octahedral
      coordination of Ti(4+) and oxygen atoms as well as an undoped titania nanosheet
      (Ti0.87O2). On the other hand, the electron transitions from 2p3/2 to 3d eg in Ti
      L3 regions are different in each nanosheet. We have also investigated the
      electron-beam-induced damage of Ti0.6Fe0.4O2 and Ti0.8Co0.2O2 nanosheets. The
      results indicated that Fe(3+) ions in the Ti0.6Fe0.4O2 nanosheets were
      selectively reduced to Fe(2+) ions in the reduction process by electron
      irradiation. In contrast, the chemical shift of the Ti-L edge of the Ti0.8Co0.2O2
      nanosheets indicated that Ti(4+) ions were reduced. These results suggest that
      the substitution of 3d metals in titania nanosheets affects their crystal and
      electronic structures and material properties such as their long-range atomic
      configuration and reduction mechanism.

PMID- 25391608
TI  - Anti-CarP antibodies as promising marker to measure joint damage and disease
      activity in patients with rheumatoid arthritis.
AB  - Anti-citrullinated protein antibodies (ACPA) are important serological markers in
      the diagnosis of rheumatoid arthritis (RA) and are part of the recent disease
      classification criteria. However, there is a strong need for reliable markers for
      measuring and predicting joint damage and disease activity. Recently, antibodies
      directed against carbamylated antigens (anti-CarP antibodies) were identified. A
      total of 120 RA patients were tested for anti-CCP antibodies using different
      methods and for anti-CarP antibodies using carbamylated fetal calf serum
      according to the method described by Shi et al. Additionally, ACPA fine
      specificities (to three citrullinated peptides) were measured. Disease activity
      was assessed at baseline using the disease activity score 28 (DAS28) in 80
      patients. For 40 RA patients, joint erosion score (JES) was established. The
      median JES was 14.1 with a standard deviation of 11.5. Anti-CarP antibodies were
      correlated with joint erosion score (rho = 0.34, 95% CI 0.03-0.59; p = 0.0332).
      No correlation between ACPA and joint erosion score was observed. No individual
      marker correlated with DAS28. When one ACPA peptide was combined with anti-CarP
      antibodies in a score (ACPA peptide 1 divided by anti-CarP), a statistically
      relevant correlation was found (p = 0.0264). In this small cohort, the presence
      of anti-CarP antibodies, but not ACPA correlate with joint erosion score. Anti
      CarP antibodies combined with ACPA fine specificities correlated with DAS28.
      Therefore, anti-CarP antibodies might represent a promising marker to predict
      joint damage and disease activity in RA patients.

PMID- 25391610
TI  - Intravenous immune globulins (IVIg) treatment for organizing pneumonia in a
      selective IgG immune deficiency state.
AB  - We describe herein a 61-year-old woman who presented with fever, night sweats and
      cough. The diagnosis of pneumonia was established, but with symptom recurrence
      following antibiotic therapy, further diagnostics were performed. Biopsy via
      bronchoscopy revealed cryptogenic organizing pneumonia, and later on follow-up, a
      selective IgG immune deficiency was also diagnosed. Initial treatment of high
      dose glucocorticoid therapy induced remission, but with dose reduction recurrence
      was observed. Intravenous immune globulin treatment was initiated and induced a
      successful clinical and radiological remission. Few cases of cryptogenic
      organizing pneumonia and hypogammaglobulinemia have been reported. To our
      knowledge, this is the fourth case described of cryptogenic organizing pneumonia
      with a hypogammaglobulinemia state and the first reported case of a selective
      immune deficiency state treated successfully with intravenous immune globulins. 

PMID- 25391609
TI  - Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict
      toxicity?
AB  - Methotrexate (MTX) is the anchor disease-modifying antirheumatic drug (DMARD) in
      rheumatoid arthritis (RA) treatment. It is used in monotherapy and/or in
      combination with other synthetic or biological DMARDs, and is known to have the
      best cost-effectiveness and efficacy/toxicity ratios. However, toxicity is still
      a concern, with a significant proportion of patients interrupting long-term
      treatment due to the occurrence of MTX-related adverse drug reactions (ADRs),
      which are the main cause of drug withdrawal. Despite the extensive accumulated
      experience in the last three decades, it is still impossible in routine clinical
      practice to identify patients prone to develop MTX toxicity. While clinical and
      biological variables, including folate supplementation, partially help to
      minimize MTX-related ADRs, the advent of pharmacogenomics could provide further
      insight into risk stratification and help to optimize drug monitoring and long
      term retention. In this paper, we aimed to review and summarize current data on
      low-dose MTX-associated toxicity, its prevention and predictors, keeping in mind
      practical RA clinical care. 

PMID- 25391611
TI  - Risk factors of systemic lupus erythematosus flares during pregnancy.
AB  - This review examines the risk factors for the development of systemic lupus
      erythematosus (SLE) flares during pregnancy. In preconception, anti-DNA,
      hypocomplementemia, previous thrombosis, triple antiphospholipid (aPL) antibody
      positivity, active lupus nephritis and discontinuation of medications such as
      hydroxychloroquine and azathioprine are factors associated with pregnancy
      failure. During pregnancy, SLE flares are associated with aPL antibodies,
      synergic changes of pregnancy on Th1 and TH2 cytokines, other cytokines and
      chemokines that interact with hormones such as estrogen and prolactin that
      amplify the inflammatory effect. From the clinical point of view, SLE activity at
      pregnancy onset, thrombocytopenia, lupus nephritis, arterial hypertension, aPL
      syndromes, preeclampsia is associated with lupus flares and fetal complications.
      In puerperium, the risk factors of flares are similar to pregnancy. Hyperactivity
      of immune system, autoantibodies, hyperprolactinemia, active lupus nephritis,
      decrease in TH2 cytokines with increase in TH1 cytokines probably participate in
      SLE flare. The SLE flares during pregnancy make the difference between an
      uncomplicated pregnancy and pregnancy with maternal and fetal complications.
      Therefore, the knowledge of risk factors leads the best treatment strategies to
      reduce flares and fetal complications in SLE patients. 

PMID- 25391612
TI  - Intravenous immunoglobulin exerts reciprocal regulation of Th1/Th17 cells and
      regulatory T cells in Guillain-Barre syndrome patients.
AB  - Guillain-Barre syndrome (GBS) is an acute, autoimmune inflammatory disorder of
      peripheral nervous system characterized by a severe functional motor weakness.
      Treatment with intravenous immunoglobulin (IVIg) is one of the approved and
      preferred therapeutic strategies for GBS. However, the mechanisms underlying the
      therapeutic benefit with IVIg in GBS are not completely understood. In the
      present study, we observed that GBS patients have increased frequencies of Th1
      and Th17 cells, but reduced number of Foxp3(+) regulatory T cells (Treg cells)
      with defective functions. We show that IVIg treatment in GBS patients results in
      a marked reduction in the frequency of Th1 and Th17 cells with a concomitant
      expansion of Treg cells. Importantly, IVIg-expanded Treg cells exhibited an
      increased T cell suppressive function. Together our results demonstrate that
      therapeutic benefit of IVIg in GBS patients implicates the reciprocal regulation
      of Th1/Th17 and Treg cells.

PMID- 25391613
TI  - The olfactory function is impaired in patients with idiopathic inflammatory
      myopathies.
AB  - The aim of our study was to analyze olfactory function in patients with
      idiopathic inflammatory myopathies (IIM). We performed a case-control study on 60
      IIM patients (48 females and 12 males) and 60 healthy controls (HC) recruited by
      the best friend method, matched for age, sex and lifestyle. Olfactory function
      was analyzed by "Sniffin' sticks test" and expressed through a score (TDI),
      indicating normosmia (TDI > 30), hyposmia (TDI 15-30) and anosmia (TDI < 15).
      Mood was investigated by Beck depression inventory (BDI) test. Statistic was
      performed using SPSS package. Mean +/- SD TDI was significantly reduced in
      patients versus HC (26.8 +/- 5.2 vs. 31.4 +/- 3.5, p < 0.001). Anosmia was
      detected in two patients (3.3 %) and no HC, hyposmia in 41 patients and 14 HC
      (68.3 vs. 23.3 %, p < 0.0001) and normosmia in 17 patients and 48 HC (28.3 vs.
      76.6 %, p < 0.0001). In the multivariate analysis carried out in the pool
      population of patients and HC, low TDI score was associated with age >=50 years
      (p < 0.0001), disease status (p < 0.0001) and high BDI (p = 0.007). When
      adjusting for BDI, disease status was still associated with low TDI (p = 0.037).
      In IIM, TDI was lower in subjects aged >=50 years (p = 0.008) and in patients who
      were taking corticosteroids (p < 0.0001). In the multivariate analysis carried
      out in IIM patients, low TDI was associated with age >=50 years (p = 0.001) and
      prednisone intake (p < 0.0001). The olfactory function is impaired in IIM
      patients. An underlying immune-mediated mechanism is conceivable, yet a possible
      interference due to age, steroid intake and depression should be considered.

PMID- 25391614
TI  - Hepatopulmonary syndrome associated with visceral leishmaniasis.
AB  - Leishmaniasis caused by Leishmania infantum is endemic in the Mediterranean
      region. Its visceral form can present a diagnostic challenge owing to the
      disease's wide spectrum of clinical presentations. We describe the very atypical
      case of a 66-year-old male Caucasian patient with hepatopulmonary syndrome and an
      exceptionally rare expression of visceral leishmaniasis in a disseminated form
      with mucocutaneous involvement presenting as an autoimmune systemic disease. 

PMID- 25391615
TI  - Population-based genetic risk prediction and stratification for ovarian cancer:
      views from women at high risk.
AB  - There is an opportunity to improve outcomes for ovarian cancer (OC) through
      advances in risk stratification, early detection and diagnosis. A population
      based OC genetic risk prediction and stratification program is being developed. A
      previous focus group study with individuals from the general population showed
      support for the proposed program. This qualitative interview study explores the
      attitudes of women at high risk of OC. Eight women participated in one-on-one, in
      depth, semi-structured interviews to explore: experiences of learning of OC risk,
      risk perceptions, OC knowledge and awareness, and opinions on risk stratification
      approach. There was evidence of strong support for the proposed program. Benefits
      were seen as providing reassurance to women at low risk, and reducing worry in
      women at high risk through appropriate clinical management. Stratification into
      'low' and 'high' risk groups was well-received. Participants were more hesitant
      about stratification to the 'intermediate' risk group. The data suggest formats
      to effectively communicate OC risk estimates will require careful thought.
      Interactions with GPs were highlighted as a barrier to OC risk assessment and
      diagnosis. These results are encouraging for the possible introduction and uptake
      of a risk prediction and stratification program for OC in the general population.

PMID- 25391616
TI  - Health professionals' evaluation of delivering treatment-focused genetic testing
      to women newly diagnosed with breast cancer.
AB  - Increasingly, women are offered genetic testing shortly after diagnosis of breast
      cancer to facilitate decision-making about treatment, often referred to as
      'treatment-focused genetic testing' (TFGT). As understanding the attitudes of
      health professionals is likely to inform its integration into clinical care we
      surveyed professionals who participated in our TFGT randomized control study.
      Thirty-six completed surveys were received (response rate 59%), 15 (42%) health
      professionals classified as genetic and 21 (58%) as non-genetic. Mainly positive
      experiences with participating in the TFGT trial were reported. The high cost of
      testing and who could best deliver information about TGFT to the patient were
      raised as key constraints to implementation of TFGT in usual care. More non
      genetic than genetic health professionals (44 vs 8%) preferred that the surgeon
      provide the information for decision-making about TFGT. While costs of TFGT
      itself and the time and effort of staff involved were perceived barriers, as
      testing costs become lower, it is expected that TFGT will become a routine part
      of standard clinical care for patients at high genetic risk in the near future.

PMID- 25391617
TI  - First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel
      Lindau (VHL) disease: clinical outcome and patterns of radiological response.
AB  - von Hippel-Lindau (VHL) is a rare hereditary condition caused by germline
      alteration of VHL gene predisposing to renal carcinoma and multiple other tumors.
      Since acquired dysregulation of VHL-dependent pathways is often present in
      patients with sporadic RCC treated with the anti-angiogenic drug sunitinib, there
      is a strong rationale to use the same drug in VHL patients with progressive
      disease in the kidneys or other sites. Our primary objective was to evaluate the
      activity of sunitinib in terms of progression-free survival. SECONDARY
      OBJECTIVES: rate of radiological response, patterns of responses in different
      organs, treatment-related toxicities. We performed a retrospective analysis of
      sunitinib therapy in genetically-confirmed VHL patients treated at our
      Institution for multifocal or advanced RCC. From February 2007 to July 2012, 14
      VHL patients started first-line sunitinib for recurrent or progressing RCC, mean
      age 48 years (27-71). Nine patients achieved a partial RECIST response (64.3%);
      responses were noted not only in renal and hepatic lesions but also in pancreatic
      nodules. Most lesions showed density reduction, while all CNS haemangioblastoma
      lesions remained stable. At a median follow-up of 37 months, six patients have
      progressed and three patients died, with a progression-free rate at 2 years of
      71.4%. Sunitinib may therefore achieve a fairly good disease control in VHL
      patients. Radiological responses may be obtained not only in renal tumors but
      also in synchronous VHL-related lesions, especially pancreatic solid nodules
      whose exact nature (metastatic RCC or neuroendocrine tumor) cannot be ruled out
      without invasive biopsy.

PMID- 25391619
TI  - A lion in winter: honoring the life and work of Robert B. Edgerton, part I.

PMID- 25391618
TI  - Disruption of polyubiquitin gene Ubb causes dysregulation of neural stem cell
      differentiation with premature gliogenesis.
AB  - Disruption of polyubiquitin gene Ubb leads to early-onset reactive gliosis and
      adult-onset hypothalamic neurodegeneration in mice. However, it remains unknown
      why reduced levels of ubiquitin (Ub) due to loss of Ubb lead to these neural
      phenotypes. To determine whether or not the defects in neurons or their
      progenitors per se, but not in their cellular microenvironment, are the cause of
      the neural phenotypes observed in Ubb(-/-) mice, we investigated the properties
      of cultured cells isolated from Ubb(-/-) mouse embryonic brains. Although cells
      were cultured under conditions promoting neuronal growth, Ubb(-/-) cells
      underwent apoptosis during culture in vitro, with increased numbers of glial
      cells and decreased numbers of neurons. Intriguingly, at the beginning of the
      Ubb(-/-) cell culture, the number of neural stem cells (NSCs) significantly
      decreased due to their reduced proliferation and their premature differentiation
      into glial cells. Furthermore, upregulation of Notch target genes due to
      increased steady-state levels of Notch intracellular domain (NICD) led to the
      dramatic reduction of proneuronal gene expression in Ubb(-/-) cells, resulting in
      inhibition of neurogenesis and promotion of gliogenesis. Therefore, our study
      suggests an unprecedented role for cellular Ub pools in determining the fate and
      self-renewal of NSCs. 

PMID- 25391620
TI  - Blocking VEGF signaling delays development of replacement teeth in zebrafish.
AB  - The dentition in zebrafish is extremely and richly vascularized, but the function
      of the vasculature, in view of the continuous replacement of the teeth, remains
      elusive. Through application of SU5416, a vascular endothelial growth factor
      receptor inhibitor, we studied the role of the blood vessels in the dentition of
      the zebrafish. We were unable to show an effect on the development of first
      generation teeth as well as first tooth replacement. However, in juvenile fish, a
      delay was observed in the developmental state of the replacement tooth compared
      with what was expected based on the maturation state of the functional tooth.
      Furthermore, we observed a difference between treated and nontreated fish in the
      distance between blood vessels and developing replacement teeth. In conclusion,
      our results provide support for a nutritive, rather than an inductive, function
      of the vasculature in the process of tooth development and replacement. 

PMID- 25391621
TI  - TRAIL-expressing gingival-derived mesenchymal stem cells inhibit tumorigenesis of
      tongue squamous cell carcinoma.
AB  - Recent research has verified that mesenchymal stromal/stem cells (MSCs) derived
      from bone marrow or adipose tissues can migrate toward a variety of tumors. In
      this study, we explored whether human gingival-derived MSCs (G-MSCs) can migrate
      toward tongue squamous cell carcinoma (TSCC) and evaluated the antitumor effect
      of engineered G-MSCs in expressing and delivering the tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL). An in vitro cell migration assay with
      Transwell plates showed that human G-MSCs can migrate toward TSCC cell lines
      (Tca8113 and Cal27). Then, human G-MSCs, as a type of cell-based vehicle, were
      transduced with full-length TRAIL and enhanced green fluorescent protein reporter
      genes by the lentivirus (LV) system (G-MSCs with full-length TRAIL; G-MSCFLT).
      Tca8113 and Cal27 were co-cultured with G-MSCFLT, respectively, to evaluate the
      function of G-MSCFLT on tumor cells in vitro. This resulted in G-MSCFLT's
      inducing a great number of tumor cell necrosis and apoptosis. Meanwhile, in vivo
      antitumor assays were performed by administering G-MSCFLT to nude mice locally
      and systematically (mixed injection with tumor cells and tail vein injection).
      This showed that G-MSCFLT can reduce or even inhibit TSCC growth regardless of
      the method of administration, especially when the mixed injection of tumor cells
      and G-MSCFLT was at a ratio of 1:1, which showed no tumor formation. Furthermore,
      this verified that G-MSCFLT migrated toward TSCC in quantity. These data
      emphasize the effectiveness of G-MSCs as a vehicle for cell-based gene therapy
      and the antitumor activity of TRAIL-expressing G-MSCs. 

PMID- 25391622
TI  - Is low back pain associated with worse health-related quality of life 6 months
      later?
AB  - PURPOSE: The purpose of this study was to investigate the impact of low back pain
      (LBP) on future health-related quality of life (HRQoL). Current evidence suggests
      that individuals with LBP have poorer HRQoL than those without LBP. However, most
      of the evidence comes from cross-sectional studies where LBP and HRQoL are
      determined at the same time. One prospective study examined the association
      between days with LBP and HRQoL but did not account for the intensity of LBP.
      Therefore, this association needs to be tested in a large prospective population
      based sample with a valid measure of LBP and adequate control of known
      confounders. METHODS: We formed a cohort of 1,110 randomly sampled Saskatchewan
      adults in September 1995. LBP at baseline was measured with the chronic pain
      questionnaire. The SF-36 questionnaire was used to measure physical and mental
      HRQoL at 6 months follow-up. Multivariable linear regression was used to estimate
      the association between graded LBP at baseline and HRQoL at 6 months while
      controlling for the effects of confounding. RESULTS: The 6-month follow-up rate
      was 70.7 % (785/1,110). LBP had a dose-response relationship with worsening
      physical HRQoL at 6 months, after controlling for age, income, arthritis, neck
      pain, and kidney disorders: grade III-IV LBP (beta = -10.23; 95 % CI -12.46, 
      7.99), grade II LBP (beta = -6.72, 95 % CI -8.79, -4.65), and grade I LBP (beta =
      -1.77; 95 % CI -3.18, -0.36). There was no dose-response relationship between LBP
      and mental HRQoL at 6 months. CONCLUSIONS: Low back pain has an impact on future
      physical HRQoL. Strategies for reducing the effects of LBP on HRQoL should be an
      important focus for clinicians, researchers, and health policy makers.

PMID- 25391623
TI  - Osteotomy of the spine for multifocal deformities.
AB  - INTRODUCTION: When a deformity involves more than one area of the spine, it
      becomes a multifocal deformity; such a deformity could either be extending on two
      adjacent segments, or be two separated deformities on two non-adjacent segments.
      MATERIALS AND METHODS: The surgical management of multifocal spinal deformities
      is challenging and must be done through a thorough preoperative planning where
      spinal and pelvic parameters should accurately be determined. Different
      strategies should be applied depending on the type of the multifocal deformity,
      the area involved, the angulation and stiffness of the spine in that area, and
      the presence of either a pure sagittal malalignment or a combined coronal and
      sagittal malalignment. This paper discusses these strategies and gives guidelines
      regarding the use of the different osteotomy techniques depending on each
      different situation that the deformity spine surgeon may encounter. For instance,
      where is the ideal level to perform a pedicle subtraction osteotomy (PSO) in a
      multifocal deformity? How does one take advantage of the remaining high discs to
      increase the correction without the need for a second PSO? When and where does
      one perform an asymmetrical PSO? When and where does one perform two PSOs? How
      does navigation help the spine surgeon to push the surgical limits further in
      these complex cases? CONCLUSION: All these questions about the management of
      multifocal deformities will be discussed and answered with technical details and
      concrete examples of the different situations that may be encountered.

PMID- 25391624
TI  - Percutaneous posterior transdiscal oblique screw fixation with lateral interbody
      fusion: a radiological and cadaveric study.
AB  - PURPOSE: To design and investigate a novel technique of percutaneous posterior
      transdiscal oblique screw fixation with lateral interbody fusion. METHODS: CT
      scans of 45 patients were collected and imported into Mimics software for three
      dimensional (3D) reconstruction. Cylinders were drawn to simulate the trajectory
      of the oblique screw. Six measurements were obtained for each unit to design a
      right size cage: a the distance between the intersection of the simulated
      trajectory of the screw with the inferior border of the upper vertebra and its
      anteroinferior corner; b the distance between the intersection of the simulated
      trajectory of the screw with the superior border of the inferior vertebra and its
      anterosuperior corner; h the height of the intervertebral space; theta the angle
      between simulated trajectory of screw and the upper endplate of inferior
      vertebra; uw: the width of the inferior endplate of upper vertebra; iw: the width
      of upper endplate of inferior vertebra. Three intact adult fresh-frozen cadaveric
      specimens were obtained, percutaneous posterior transdiscal oblique screw
      fixation was performed under X-ray apparatus, and interbody cage was implanted by
      assistance with special self-retaining retractor system and endoscope. RESULTS:
      According to the results of data measured from 3D images, trapezoid shape
      interbody cages with suitable size were designed. Percutaneous posterior oblique
      screw fixation with lateral interbody fusion was performed on three cadaveric
      specimens successfully. CONCLUSION: Using specially designed trapezoid shape
      interbody cages, assisted by intra-operative image intensification and endoscope,
      it is feasible to perform percutaneous posterior transdiscal oblique screw
      fixation with lateral interbody fusion technique.

PMID- 25391625
TI  - A validation of the Oswestry Spinal Risk Index.
AB  - PURPOSE: The purpose of this study was to validate the Oswestry Spinal Risk Index
      (OSRI) in an external population. The OSRI predicts survival in patients with
      metastatic spinal cord compression (MSCC). METHODS: We analysed the data of 100
      patients undergoing surgical intervention for MSCC at a tertiary spinal unit and
      recorded the primary tumour pathology and Karnofsky performance status to
      calculate the OSRI. Logistic regression models and survival plots were applied to
      the data in accordance with the original paper. RESULTS: Lower OSRI scores
      predicted longer survival. The OSRI score predicted survival accurately in 74% of
      cases (p = 0.004). CONCLUSIONS: Our study has found that the OSRI is a
      significant predictor of survival at levels similar to those of the original
      authors and is a useful and simple tool in aiding complex decision making in
      patients presenting with MSCC.

PMID- 25391626
TI  - Whole cerebrospinal axis infection after lumbar epidural injection: a case
      report.
AB  - PURPOSE: Lumbar epidural injection is a popular treatment for degenerative lumbar
      disease. Although post-procedural epidural infection is rare, meningitis and
      epidural abscess are life-threatening conditions, and need additional medical and
      surgical intervention. The purpose of this article is to report a patient with
      fatal whole cerebrospinal axis infection after lumbar epidural injections.
      METHODS: A 64-year-old female patient presented with septic shock and
      quadriparesis. In the past, this patient had received lumbar epidural injections
      several times for degenerative spondylolisthesis at L4-5 in another hospital. The
      magnetic resonance imaging showed epidural abscess, a compressed dura and spinal
      cord from C1 to S2, and cerebral meningitis. We performed laminectomies and
      removal of the abscesses. Her mental status was diminished to a deep, drowsy
      state after three postoperative weeks. Brain computed tomography scans revealed
      hydrocephalus. Therefore, ventriculoperitoneal shunting was performed. RESULTS:
      Methicillin resistant Staphylococcus epidermidis was cultured from blood samples.
      The patient's infection was completely controlled and her mental status improved
      to alert; however, her quadriparesis remained. CONCLUSIONS: Although lumbar
      epidural injection is an effective procedure to treat lumbar radicular pain, this
      procedure can induce fatal complications such as sepsis and epidural abscess.
      LEVEL OF EVIDENCE: 5.

PMID- 25391627
TI  - Asymmetrical pedicle subtraction osteotomy in the lumbar spine in combined
      coronal and sagittal imbalance.
AB  - INTRODUCTION: Degenerative scoliosis is a three-dimensional deformity that can
      present in some instances with fixed sagittal and coronal imbalance. Pedicle
      subtraction osteotomy (PSO) is an effective technique that allows correction with
      a posterior approach. When a combined coronal and sagittal imbalance is present,
      asymmetric PSOs could be an optimal choice to correct deformity on both planes.
      METHODS: The asymmetric wedge resected from the vertebral body has to be shorter
      in the side of coronal imbalance, while a higher side cut has to be performed in
      the site opposite to the coronal imbalance. This allows to restore both coronal
      and sagittal alignment after osteotomy closure. An adequate preoperative planning
      is mandatory to correctly assess the geometry of the wedge to obtain the
      necessary correction. CONCLUSIONS: The few studies present in literature show
      good results in terms of correction, even if the difficulty of this technique is
      certain.

PMID- 25391628
TI  - Metabolic syndrome and the environmental pollutants from mitochondrial
      perspectives.
AB  - The worldwide epidemic of diabetes and metabolic syndrome in the last few decades
      cannot be fully accounted for only by changes in the lifestyle factors, such as
      sedentary lifestyle and overeating. Besides genetic factors, there must be other
      causes to explain this rapid change. They could not be infectious in nature and
      induce insulin resistance as key biochemical abnormality. Mitochondrial
      dysfunction could be underlying mechanism behind the insulin resistance, thus
      metabolic syndrome. Then there have been increasing number of reports suggesting
      that chronic exposure to and accumulation of endocrine disrupting chemicals
      (EDCs), especially so-called the persistent organic pollutants (POPs) within the
      body might be associated with metabolic syndrome. Combining two concepts, we
      developed new "EDCs-induced mitochondrial dysfunction hypothesis of metabolic
      syndrome". In this review we suggest that classifying those chemicals into 5
      groups might be clinically useful considering their removal or avoidance; POPs,
      non-persistent organic pollutants, heavy metals, air pollutants and drugs. We
      will also discuss briefly how those insights could be applied to clinical
      medicine. 

PMID- 25391629
TI  - Dose intraarticular steroid injection increase the rate of infection in
      subsequent arthroplasty: grading the evidence through a meta-analysis.
AB  - BACKGROUND: Intraarticular steroid injections are widely used in joint arthritis.
      However, the data regarding an association between an increased risk for
      arthroplasty infection after an intraarticular steroid injection are still
      conflicting. We conducted a meta-analysis to evaluate the evidence from relevant
      studies that examine the relation between intraarticular steroid injections and
      infection rates in subsequent joint arthroplasty and to develop GRADE based
      recommendations for using the steroid before arthroplasty. METHODS: A systematic
      search of all studies published through August 2014 was conducted using the
      MEDLINE, EMBASE, OVID, ScienceDirect and Cochrane CENTRAL databases. The relevant
      studies that examined the relation between intraarticular steroid injections and
      infection rates in subsequent joint arthroplasty were identified. Demographic
      characteristics, infection rates and clinical outcomes were manually extracted
      from all of the selected studies. The evidence quality levels and recommendations
      were assessed using the GRADE system. RESULTS: Eight studies looking at hip and
      knee arthroplasties were included. Meta-analysis showed that patients with
      steroid injection before arthroplasty had a higher deep infection rate than
      patients without steroid injection (OR = 2.13, 95% CI 1.02-4.45), but no
      significant effect on superficial infection rate (OR = 1.75, 95% CI 0.74-4.16).
      The overall GRADE system evidence quality was very low, which lowers our
      confidence in their recommendations. CONCLUSIONS: Intraarticular steroid
      injections may lead to increased deep infection rates of subsequent joint
      arthroplasty but not the superficial infection rates. Due to the poor quality of
      the evidence currently available, further studies are still required.

PMID- 25391630
TI  - Sudden cardiac death in end stage renal disease: unlocking the mystery.
AB  - Sudden cardiac death (SCD) is a major cause of concern in end stage renal disease
      (ESRD), contributing to 70% of cardiovascular mortality and 27% of all-cause
      mortality in dialysis patients. Yet its mechanisms and pathogenesis remain
      largely obscure. This review discusses the potential reasons for an exaggerated
      risk of SCD in ESRD populations taking into account recent studies and registry
      data and additionally explores the reasons for the reported recent decline in
      SCD. The types of arrhythmias typical of the hemodialysis population are yet to
      be fully characterised and in this paper, we introduce an ongoing implantable
      loop recorder (ILR) based study in hemodialysis patients--CRASH ILR (Cardio Renal
      Arrhythmia Study in Haemodialysis patients using Implantable Loop Recorders). The
      findings of this study will hopefully guide the design and implementation of
      larger ILR based studies before undertaking larger scale interventional
      therapeutic trials in this high risk population.

PMID- 25391631
TI  - Thermal expansion anomaly regulated by entropy.
AB  - Thermal expansion, defined as the temperature dependence of volume under constant
      pressure, is a common phenomenon in nature and originates from anharmonic lattice
      dynamics. However, it has been poorly understood how thermal expansion can show
      anomalies such as colossal positive, zero, or negative thermal expansion (CPTE,
      ZTE, or NTE), especially in quantitative terms. Here we show that changes in
      configurational entropy due to metastable micro(scopic)states can lead to
      quantitative prediction of these anomalies. We integrate the Maxwell relation,
      statistic mechanics, and first-principles calculations to demonstrate that when
      the entropy is increased by pressure, NTE occurs such as in Invar alloy (Fe3Pt,
      for example), silicon, ice, and water, and when the entropy is decreased
      dramatically by pressure, CPTE is expected such as in anti-Invar cerium, ice and
      water. Our findings provide a theoretic framework to understand and predict a
      broad range of anomalies in nature in addition to thermal expansion, which may
      include gigantic electrocaloric and electromechanical responses, anomalously
      reduced thermal conductivity, and spin distributions. 

PMID- 25391632
TI  - Multilevel mini-open TLIFs and percutaneous pedicle screw fixation: description
      of a simple technical nuance used to increase intraoperative safety and improve
      workflow. Tips and tricks and review of the literature.
AB  - We describe a technical variation used to enhance intraoperative safety and
      efficiency in multilevel percutaneous pedicle screw fixation (PPSFs) and mini
      open transforaminal lumbar interbody fusion (m-TLIFs). A review of the literature
      on percutaneous screw insertion techniques and related pitfalls is presented.
      PPSFs and m-TLIFs are increasingly used techniques in multilevel lumbar
      degenerative disease. Facetectomy and TLIF are usually performed before inserting
      ipsilateral pedicle screws. Such techniques can cause unintended violation of the
      pedicle and injure the dura or neural structures, particularly in multilevel
      cases. A literature review revealed a lack of intraoperative and fluoroscopic
      images detailing the technique for multilevel PPSF and m-TLIF(s) performed
      through tubular, expandable retractors. Thirteen patients with two- to four-level
      disease underwent multilevel PPSF and m-TLIF (one to four levels). The Kirschner
      Cage Screw (KCS) technique, consisting of early insertion of K-wires in all
      pedicles followed by facetectomy and m-TLIF(s) and, finally, screw insertion, was
      used in order to minimize the risk of dural/neural injuries. Neither CSF
      (cerebrospinal fluid) leaks nor nerve root injuries nor technique-related
      complications were encountered with a follow-up ranging from 7 to 38 months (mean
      23.6). In conclusion, the KCS technique allows safe identification of the
      pedicles without opening the canal during m-TLIF(s). Moreover, by visualizing the
      K-wires inside the retractor, the surgeon can check the pedicle position during
      facetectomy, and screws can be introduced with a minimal risk of neural or dural
      injuries. We believe that the proposed technique increases the safety and ease of
      the procedure, particularly in multilevel cases.

PMID- 25391633
TI  - Use of remote response devices: an effective interactive method in the long- term
      learning.
AB  - OBJECTIVES: The aim of this study was to evaluate whether the use of personal
      response systems (PRS) or clickers improved learning and retention of radiology
      concepts within a group of medical students. MATERIALS AND METHODS: A total of
      175 medical students attended 17 thoracic radiology lectures. Half of the
      information was taught with traditional teaching methods. The other half was
      performed using multiple-choice Power Point slides with PRS. Three months later,
      the students were tested using questions about the topics explained with and
      without PRS. We compared the average numbers of correct answers, wrong answers
      and unanswered questions between the topics explained with PRS and those without.
      RESULTS: The average number of correct answers was significantly higher in the
      interactive teaching (PRS) questions than in the passive education questions
      (63.6 vs. 53.2 %, p < 0.05). The percentages of wrong and unanswered interactive
      teaching questions were significantly lower than those in the passive education
      questions (23.4 vs. 27.4 % p < 0.005 and 13 vs. 19.5 % p < 0.005 respectively).
      CONCLUSIONS: Interactive learning with the use of remote response devices (PRS)
      is an effective method in teaching radiology because it improves learning and
      retention of knowledge.

PMID- 25391634
TI  - A single codon insertion in the PICALM gene is not associated with subvalvular
      aortic stenosis in Newfoundland dogs.

PMID- 25391635
TI  - Epidemic of complicated mumps in previously vaccinated young adults in the South
      West of France.
AB  - OBJECTIVE: We report the features and diagnosis of complicated mumps in
      previously vaccinated young adults. PATIENTS AND METHODS: We retrospectively
      studied 7 cases of complicated mumps managed during 1 year at the Bordeaux
      University Hospital. The diagnosis was suggested by the clinical presentation and
      confirmed using specific RT-PCR. RESULTS: Five cases of meningitis, 1 of
      orchitis, and 1 of unilateral hearing impairment were identified. Each of the 7
      patients had been previously vaccinated with MMR, 4 had received 2 doses of this
      vaccine. Blood tests revealed high rates of IgG antibodies, usually considered as
      sufficient for immunological protection, and every patient had at least 1
      positive RT-PCR test for mumps. CONCLUSION: Outbreaks of complicated mumps may
      still occur despite a broad coverage of MMR vaccination. The clinical
      presentation suggested mumps but the final diagnosis could only be confirmed by
      genomic detection of the virus. Unusual viral strains with increased
      neurovirulence, insufficient population coverage associated with immunity
      decrease over time may explain outbreaks of complicated mumps. A full vaccine
      scheme of contact people or a third injection of vaccine for previously
      vaccinated people who are at risk of developing mumps are required to prevent
      further spreading of the disease during the outbreak.

PMID- 25391637
TI  - Personality, fear of childbirth and birth outcomes in nulliparous women.
AB  - PURPOSE: This study was aimed at investigating the delivery continuum starting
      from constant personality variables and their association with Fear of childbirth
      (FOC) pre-partum, following the association of FOC pre-partum with the delivery
      process (as measured by birth outcome variables and subjective experience) and
      the effect of all of these variables over FOC post-partum. METHODS: In this
      prospective questionnaire study, 101 nulliparous, singleton pregnancy, healthy
      parturients were randomly recruited during 2011. Questionnaires were administered
      on admittance to the delivery ward (FOC, anxiety-sensitivity index, demographic
      information) and 2 days post-partum (FOC, Big five inventory and a question
      regarding the birth experience). Medical Variables were taken from medical
      records. RESULTS: FOC pre- and post-partum were associated with neuroticism (p <
      0.05; p < 0.01) and anxiety sensitivity (p < 0.01). FOC pre-partum was correlated
      with mode of delivery, higher FOC pre-partum associated with instrumental
      delivery and emergency CS (p < 0.01). FOC post-partum was associated with both
      mode of delivery and length of the second phase of delivery (p < 0.05).
      Hierarchical regression analysis showed FOC pre-partum (beta = 0.35, p < 0.01),
      anxiety sensitivity (beta = 0.38, p < 0.01), mode of delivery (beta = 0.19, p <
      0.05) and birth experience (beta = -0.17, p < 0.05) as major predictors for high
      FOC post-partum explaining 61 % of variance (F (7,84) = 16.82; p < 0.001).
      CONCLUSIONS: The difference between FOC levels pre- and post-partum was
      associated with personality variables and birth outcomes resulting in a model
      describing the variance in FOC post-partum by all of the above mentioned
      variables. As the implications of FOC over delivery outcomes are evident, women
      suffering from FOC pre-partum should be screened routinely before delivery and
      offered proper care.

PMID- 25391638
TI  - Vaginal cesarean section: heir to, but not legacy of Duhrssen's incision.
AB  - PURPOSE: Vaginal cesarean section is a uterine incision technique derived from
      Duhrssen's incision, with which it is sometimes confused. We report here our
      experience over 10 years with this technique, with the aim of defining the
      situations in which it is potentially useful. METHODS: We retrospectively
      analyzed 24 cases of vaginal cesarean section (i.e. cervico-segmental incision)
      carried out from 2002 to 2011 in our tertiary maternity unit. This corresponds to
      an incidence of 1.1 per thousand deliveries. The main outcome measures were the
      indications and complications of vaginal cesarean section. RESULTS: The study
      population included 42% nulliparous women. The fetuses concerned had a median
      gestational age of 24 weeks + 5 days (18 to 34 weeks + 1 day) and a median weight
      of 595 g (340-1,250 g). The indications for vaginal cesarean section were severe
      maternal morbidity in 54.2% of cases, failed labor induction in 29.2% and another
      indication in 16.7%. All but one of the fetuses were dead or nonviable. Surgical
      complications were observed in three cases: two difficulties achieving hemostatic
      control and one bladder injury. CONCLUSIONS: Vaginal cesarean section is
      sometimes considered obsolete, but it has several advantages: technical
      simplicity, limited tissue dissection, low risk of hemorrhage and no abdominal
      scar. These features make it particularly suitable for the extraction of medium
      sized dead or nonviable fetuses when pharmacological options are ineffective or
      not rapid enough in cases of poor maternal condition.

PMID- 25391636
TI  - Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting
      BET proteins and epigenetic regulation.
AB  - Emerging evidence suggests that RANKL-induced changes in chromatin state are
      important for osteoclastogenesis, but these epigenetic mechanisms are not well
      understood and have not been therapeutically targeted. In this study, we find
      that the small molecule I-BET151 that targets bromo and extra-terminal (BET)
      proteins that 'read' chromatin states by binding to acetylated histones strongly
      suppresses osteoclastogenesis. I-BET151 suppresses pathologic bone loss in TNF
      induced inflammatory osteolysis, inflammatory arthritis and post-ovariectomy
      models. Transcriptome analysis identifies a MYC-NFAT axis important for
      osteoclastogenesis. Mechanistically, I-BET151 inhibits expression of the master
      osteoclast regulator NFATC1 by suppressing expression and recruitment of its
      newly identified upstream regulator MYC. MYC is elevated in rheumatoid arthritis
      macrophages and its induction by RANKL is important for osteoclastogenesis and
      TNF-induced bone resorption. These findings highlight the importance of an I
      BET151-inhibited MYC-NFAT axis in osteoclastogenesis, and suggest targeting
      epigenetic chromatin regulators holds promise for treatment of inflammatory and
      oestrogen deficiency-mediated pathologic bone resorption. 

PMID- 25391639
TI  - The role of preventive uterine artery occlusion during laparoscopic myomectomy: a
      review of the literature.
AB  - PURPOSE: Surgical myomectomy is currently regarded as the standard conservative
      treatment for patients who wish to preserve their fertility. However, it presents
      two main problems: the intra- and postoperative risk of bleeding and the risk of
      recurrence of leiomyomas. Preventive occlusion of uterine arteries was described
      during laparoscopic myomectomy as one of the procedures addressing these issues.
      METHODS: We conducted a literature review to define the role of preventive
      uterine artery occlusion during laparoscopic myomectomy. RESULTS: Nine non
      randomized case-control studies and two randomized controlled trials were
      identified. The permanent and bilateral uterine artery occlusion technique is the
      most studied in the literature. The main purpose of facilitating the operative
      procedure by reducing blood loss has not been clearly demonstrated in randomized
      trials. Observational comparative studies found an improvement in the
      effectiveness of treatment, both on clinical symptoms and on the recurrence of
      leiomyomas. Finally, there are few data examining the effect of uterine artery
      occlusion on later fertility in female patients of childbearing age, which limits
      its current use. CONCLUSION: The preventive occlusion of uterine arteries is a
      safe surgical technique that can be performed during laparoscopic myomectomy.
      Further randomized studies are needed to better define the role of uterine artery
      occlusion in the surgical strategy, especially for women who want to preserve
      their fertility.

PMID- 25391640
TI  - Repeated measures study of weekly and daily cytomegalovirus shedding patterns in
      saliva and urine of healthy cytomegalovirus-seropositive children.
AB  - BACKGROUND: To better understand potential transmission risks from contact with
      the body fluids of children, we monitored the presence and amount of CMV shedding
      over time in healthy CMV-seropositive children. METHODS: Through screening we
      identified 36 children from the Atlanta, Georgia area who were CMV-seropositive,
      including 23 who were shedding CMV at the time of screening. Each child received
      12 weekly in-home visits at which field workers collected saliva and urine.
      During the final two weeks, parents also collected saliva and urine daily.
      RESULTS: Prevalence of shedding was highly correlated with initial shedding
      status: children shedding at the screening visit had CMV DNA in 84% of follow-up
      saliva specimens (455/543) and 28% of follow-up urine specimens (151/539); those
      not shedding at the screening visit had CMV DNA in 16% of follow-up saliva
      specimens (47/303) and 5% of follow-up urine specimens (16/305). Among positive
      specimens we found median viral loads of 82,900 copies/mL in saliva and 34,730
      copies/mL in urine (P=0.01), while the viral load for the 75th percentile was
      nearly 1.5 million copies/mL for saliva compared to 86,800 copies/mL for urine.
      Younger age was significantly associated with higher viral loads, especially for
      saliva (P<0.001). Shedding prevalence and viral loads were relatively stable over
      time. All children who were shedding at the screening visit were still shedding
      at least some days during weeks 11 and 12, and median and mean viral loads did
      not change substantially over time. CONCLUSIONS: Healthy CMV-seropositive
      children can shed CMV for months at high, relatively stable levels. These data
      suggest that behavioral prevention messages need to address transmission via both
      saliva and urine, but also need to be informed by the potentially higher risks
      posed by saliva and by exposures to younger children.

PMID- 25391641
TI  - Pharmacogenetics of CYP2B6, CYP2A6 and UGT2B7 in HIV treatment in African
      populations: focus on efavirenz and nevirapine.
AB  - The CYP450 and UGT enzymes are involved in phase I and phase II metabolism of the
      majority of clinically prescribed drugs, including the non-nucleoside reverse
      transcriptase inhibitors, efavirenz and nevirapine, used in the treatment of
      HIV/AIDS. Variations in the activity of these enzymes due to gene polymorphisms
      can affect an individual's drug response or may lead to adverse drug reactions.
      There is an inter-ethnic distribution in the frequency of these polymorphisms,
      with African populations exhibiting higher genetic diversity compared to other
      populations. African specific alleles with clinical relevance have also emerged.
      Given the high prevalence of HIV/AIDS in sub-Saharan Africa, understanding the
      frequency of pharmacogenetically relevant alleles in populations of African
      origin, and their impact on efavirenz and nevirapine metabolism, is becoming
      increasingly critical. This review aims to investigate ethnic variation of
      CYP2B6, CYP2A6 and UGT2B7, and to understand the pharmacogenetic relevance when
      comparing frequencies in African populations to other populations worldwide. 

PMID- 25391642
TI  - Immunization with advanced glycation end products modified low density
      lipoprotein inhibits atherosclerosis progression in diabetic apoE and LDLR null
      mice.
AB  - BACKGROUND: Diabetes accelerates atherosclerosis through undefined molecular
      mechanisms. Hyperglycemia induces formation of advanced glycation end product
      (AGE)-modified low-density lipoprotein (LDL). Anti-AGE-LDL autoantibodies favor
      atherosclerosis (AS) progression in humans, while anti oxidized LDL immunization
      inhibits AS in hypercholesterolemic, non-diabetic mice. We here investigated if
      AGE-LDL immunization protects against AS in diabetic mice. METHODS: After
      diabetes induction with streptozotocin and high fat diet, both low density
      lipoprotein receptor (LDLR)-/- and apoE female mice were randomized to: AGE-LDL
      immunization with aluminum hydroxide (Alum) adjuvant; Alum alone; or PBS.
      RESULTS: AGE-LDL immunization: significantly reduced AS; induced specific plasma
      IgM and IgG antibodies; upregulated splenic Th2, Treg and IL-10 levels, without
      altering Th1 or Th17 cells; and increased serum high density lipoprotein(HDL)
      while numerically lowering HbA1c levels. CONCLUSIONS: Subcutaneous immunization
      with AGE-LDL significantly inhibits atherosclerosis progression in hyperlipidemic
      diabetic mice possibly through activation of specific humoral and cell mediated
      immune responses and metabolic control improvement.

PMID- 25391643
TI  - Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell
      formation by modulating genes involved in plaque stability, lipid homeostasis and
      inflammation.
AB  - In the present study, the anti-atherosclerotic effect and the underlying
      mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma
      longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in
      THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid
      ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1
      week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100
      and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5
      weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at
      5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg)
      reduced elevated plasma and aortic lipid levels, arterial macrophage
      accumulation, and stenosis when compared with those subjected to arterial injury
      alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP
      2), MMP-9, cluster of differentiation 45 (CD45), TNF-alpha, interferon-gamma (IFN
      gamma), IL-1beta and IL-6 were reduced in atherosclerotic arteries, while those
      of transforming growth factor-beta (TGF-beta) and IL-10 were increased after the
      C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and
      oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of
      CD68 and CD36, and increased the mRNA expression of PPARalpha, LXRalpha, ABCA1
      and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1
      macrophages. The administration of C. oil suppressed the mRNA expression of TNF
      alpha, IL-1beta, IL-6 and IFN-gamma and increased the expression of TGF-beta in
      peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented
      OxLDL-induced production of TNF-alpha and IL-1beta and increased the levels of
      TGF-beta. The present study shows that C. oil attenuates arterial injury-induced
      accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

PMID- 25391644
TI  - Concise review: engineering the fusion of cytokines for the modulation of immune
      cellular responses in cancer and autoimmune disorders.
AB  - As our understanding of the basic precepts of immunobiology continue to advance
      at a rapid pace, translating such discoveries into meaningful therapies for
      patients has proved challenging. This is especially apparent in the use of
      cytokine-based immunotherapies for cancer. Unanticipated and serious side
      effects, as well as low objective response rates seen in clinical trials, have
      dealt setbacks to the field. Granulocyte-macrophage colony-stimulating factor (GM
      CSF) and common gamma-chain (gamma-c) interleukins are cytokines that have been
      used as stand-alone immunotherapies with moderate success. Our group has found
      that the fusion of GM-CSF to members of gamma-c interleukins results in the
      generation of novel proteins with unique signaling properties and unheralded
      biological effects. These fusion proteins, termed GIFT (GM-CSF interleukin fusion
      transgenes) fusokines, are the result of combining GM-CSF and a gamma-c
      interleukin into a single, bifunctional polypeptide. In our experience, GIFT
      fusokines often confer immune cells with a gain of function that cannot be
      explained by the mere sum of their constituent moieties. They act as bispecific
      ligands, coupling activated GM-CSF and interleukin receptors together to drive
      unique downstream signaling events. The synergy that arises from these fusions
      has shown great promise in its ability to modulate the immune response and
      overcome maladaptive biological processes that underlie diseases such as cancer
      and autoimmune conditions. In this review, we discuss the ways in which the GIFT
      fusokines are able to alter the immune response, particularly in disease states,
      with a special emphasis on how these novel molecules may be translated into
      effective therapies in the clinical setting. 

PMID- 25391645
TI  - Concise review: mesoangioblast and mesenchymal stem cell therapy for muscular
      dystrophy: progress, challenges, and future directions.
AB  - Mesenchymal stem cells (MSCs) and mesoangioblasts (MABs) are multipotent cells
      that differentiate into specialized cells of mesodermal origin, including
      skeletal muscle cells. Because of their potential to differentiate into the
      skeletal muscle lineage, these multipotent cells have been tested for their
      capacity to participate in regeneration of damaged skeletal muscle in animal
      models of muscular dystrophy. MSCs and MABs infiltrate dystrophic muscle from the
      circulation, engraft into host fibers, and bring with them proteins that replace
      the functions of those missing or truncated. The potential for systemic delivery
      of these cells increases the feasibility of stem cell therapy for the large
      numbers of affected skeletal muscles in patients with muscular dystrophy. The
      present review focused on the results of preclinical studies with MSCs and MABs
      in animal models of muscular dystrophy. The goals of the present report were to
      (a) summarize recent results, (b) compare the efficacy of MSCs and MABs derived
      from different tissues in restoration of protein expression and/or improvement in
      muscle function, and (c) discuss future directions for translating these
      discoveries to the clinic. In addition, although systemic delivery of MABs and
      MSCs is of great importance for reaching dystrophic muscles, the potential
      concerns related to this method of stem cell transplantation are discussed. 

PMID- 25391646
TI  - Defining the optimal window for cranial transplantation of human induced
      pluripotent stem cell-derived cells to ameliorate radiation-induced cognitive
      impairment.
AB  - Past preclinical studies have demonstrated the capability of using human stem
      cell transplantation in the irradiated brain to ameliorate radiation-induced
      cognitive dysfunction. Intrahippocampal transplantation of human embryonic stem
      cells and human neural stem cells (hNSCs) was found to functionally restore
      cognition in rats 1 and 4 months after cranial irradiation. To optimize the
      potential therapeutic benefits of human stem cell transplantation, we have
      further defined optimal transplantation windows for maximizing cognitive benefits
      after irradiation and used induced pluripotent stem cell-derived hNSCs (iPSC
      hNSCs) that may eventually help minimize graft rejection in the host brain. For
      these studies, animals given an acute head-only dose of 10 Gy were grafted with
      iPSC-hNSCs at 2 days, 2 weeks, or 4 weeks following irradiation. Animals
      receiving stem cell grafts showed improved hippocampal spatial memory and
      contextual fear-conditioning performance compared with irradiated sham-surgery
      controls when analyzed 1 month after transplantation surgery. Importantly,
      superior performance was evident when stem cell grafting was delayed by 4 weeks
      following irradiation compared with animals grafted at earlier times. Analysis of
      the 4-week cohort showed that the surviving grafted cells migrated throughout the
      CA1 and CA3 subfields of the host hippocampus and differentiated into neuronal
      (~39%) and astroglial (~14%) subtypes. Furthermore, radiation-induced
      inflammation was significantly attenuated across multiple hippocampal subfields
      in animals receiving iPSC-hNSCs at 4 weeks after irradiation. These studies
      expand our prior findings to demonstrate that protracted stem cell grafting
      provides improved cognitive benefits following irradiation that are associated
      with reduced neuroinflammation. 

PMID- 25391647
TI  - A new schistosomicidal and antioxidative phenylpropanoid from Astragalus
      englerianus.
AB  - A new phenylpropanoid, (E)-2,3,4-trimethoxy-5-(1-propenyl)phenol (1), along with
      five known aromatic compounds (2-6), was isolated from the methanol extract of
      roots of Astragalus englerianus. Their structures were elucidated based on the
      analyses of extensive spectroscopic data and comparison of their physicochemical
      properties. Compounds 1 and 2 were evaluated schistosomicidal activities, and all
      the isolated compounds were tested for their antioxidant activities in vitro.
      Compound 1 showed significant schistosomicidal activity with worm mortality rates
      of 66.7% and 83.3% within 12 and 24 h in a drug-containing (1.16 mM) RPMI 1640
      medium, respectively. Also, compound 1 exhibited excellent antioxidant activity
      (2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl free radical-scavenging
      capability) with an IC50 value of 81.3 +/- 1.3 MUM. 

PMID- 25391648
TI  - Complexity of danger: the diverse nature of damage-associated molecular patterns.
AB  - In reply to internal or external danger stimuli, the body orchestrates an
      inflammatory response. The endogenous triggers of this process are the damage
      associated molecular patterns (DAMPs). DAMPs represent a heterogeneous group of
      molecules that draw their origin either from inside the various compartments of
      the cell or from the extracellular space. Following interaction with pattern
      recognition receptors in cross-talk with various non-immune receptors, DAMPs
      determine the downstream signaling outcome of septic and aseptic inflammatory
      responses. In this review, the diverse nature, structural characteristics, and
      signaling pathways elicited by DAMPs will be critically evaluated. 

PMID- 25391649
TI  - Sequence-dependent internalization of aggregating peptides.
AB  - Recently, a number of aggregation disease polypeptides have been shown to spread
      from cell to cell, thereby displaying prionoid behavior. Studying aggregate
      internalization, however, is often hampered by the complex kinetics of the
      aggregation process, resulting in the concomitant uptake of aggregates of
      different sizes by competing mechanisms, which makes it difficult to isolate
      pathway-specific responses to aggregates. We designed synthetic aggregating
      peptides bearing different aggregation propensities with the aim of producing
      modes of uptake that are sufficiently distinct to differentially analyze the
      cellular response to internalization. We found that small acidic aggregates
      (<=500 nm in diameter) were taken up by nonspecific endocytosis as part of the
      fluid phase and traveled through the endosomal compartment to lysosomes. By
      contrast, bigger basic aggregates (>1 MUm) were taken up through a mechanism
      dependent on cytoskeletal reorganization and membrane remodeling with the
      morphological hallmarks of phagocytosis. Importantly, the properties of these
      aggregates determined not only the mechanism of internalization but also the
      involvement of the proteostatic machinery (the assembly of interconnected
      networks that control the biogenesis, folding, trafficking, and degradation of
      proteins) in the process; whereas the internalization of small acidic aggregates
      is HSF1-independent, the uptake of larger basic aggregates was HSF1-dependent,
      requiring Hsp70. Our results show that the biophysical properties of aggregates
      determine both their mechanism of internalization and proteostatic response. It
      remains to be seen whether these differences in cellular response contribute to
      the particular role of specific aggregated proteins in disease. 

PMID- 25391650
TI  - Epigenetic modification of histone 3 lysine 27: mediator subunit MED25 is
      required for the dissociation of polycomb repressive complex 2 from the promoter
      of cytochrome P450 2C9.
AB  - The Mediator complex is vital for the transcriptional regulation of eukaryotic
      genes. Mediator binds to nuclear receptors at target response elements and
      recruits chromatin-modifying enzymes and RNA polymerase II. Here, we examine the
      involvement of Mediator subunit MED25 in the epigenetic regulation of human
      cytochrome P450 2C9 (CYP2C9). MED25 is recruited to the CYP2C9 promoter through
      association with liver-enriched HNF4alpha, and we show that MED25 influences the
      H3K27 status of the HNF4alpha binding region. This region was enriched for the
      activating marker H3K27ac and histone acetyltransferase CREBBP after MED25
      overexpression but was trimethylated when MED25 expression was silenced. The
      epigenetic regulator Polycomb repressive complex (PRC2), which represses
      expression by methylating H3K27, plays an important role in target gene
      regulation. Silencing MED25 correlated with increased association of PRC2 not
      only with the promoter region chromatin but with HNF4alpha itself. We confirmed
      the involvement of MED25 for fully functional preinitiation complex recruitment
      and transcriptional output in vitro. Formaldehyde-assisted isolation of
      regulatory elements (FAIRE) revealed chromatin conformation changes that were
      reliant on MED25, indicating that MED25 induced a permissive chromatin state that
      reflected increases in CYP2C9 mRNA. For the first time, we showed evidence that a
      functionally relevant human gene is transcriptionally regulated by HNF4alpha via
      MED25 and PRC2. CYP2C9 is important for the metabolism of many exogenous
      chemicals including pharmaceutical drugs as well as endogenous substrates. Thus,
      MED25 is important for regulating the epigenetic landscape resulting in
      transcriptional activation of a highly inducible gene, CYP2C9.

PMID- 25391651
TI  - miR-193a-3p functions as a tumor suppressor in lung cancer by down-regulating
      ERBB4.
AB  - ERBB4, one of four ErbB receptor tyrosine kinase family members, plays an
      important role in the etiology and progression of lung cancer. In this study, we
      found that the ERBB4 protein levels were consistently up-regulated in lung cancer
      tissues, whereas the mRNA levels varied randomly, suggesting that a post
      transcriptional mechanism was involved in regulating ERBB4 expression. Because
      microRNAs are powerful post-transcriptional regulators of gene expression, we
      used bioinformatic analyses to search for microRNAs that can potentially target
      ERBB4. We identified specific targeting sites for miR-193a-3p in the 3'-UTR of
      ERBB4. We further identified an inverse correlation between miR-193a-3p levels
      and ERBB4 protein levels, but not mRNA levels, in lung cancer tissue samples. By
      overexpressing or knocking down miR-193a-3p in lung cancer cells, we
      experimentally confirmed that miR-193a-3p directly recognizes the 3'-UTR of the
      ERBB4 transcript and regulates ERBB4 expression. Furthermore, the biological
      consequences of the targeting of ERBB4 by miR-193a-3p were examined in vitro via
      cell proliferation, invasion, and apoptosis assays and in vivo using a mouse
      xenograft tumor model. We demonstrated that the repression of ERBB4 by miR-193a
      3p suppressed proliferation and invasion and promoted apoptosis in lung cancer
      cells and that miR-193a-3p exerted an anti-tumor effect by negatively regulating
      ERBB4 in xenograft mice. Taken together, our findings provide the first clues
      regarding the role of miR-193a-3p as a tumor suppressor in lung cancer through
      the inhibition of ERBB4 translation. 

PMID- 25391653
TI  - Selective inhibition of mutant isocitrate dehydrogenase 1 (IDH1) via disruption
      of a metal binding network by an allosteric small molecule.
AB  - Cancer-associated point mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and
      IDH2) confer a neomorphic enzymatic activity: the reduction of alpha
      ketoglutarate to d-2-hydroxyglutaric acid, which is proposed to act as an
      oncogenic metabolite by inducing hypermethylation of histones and DNA. Although
      selective inhibitors of mutant IDH1 and IDH2 have been identified and are
      currently under investigation as potential cancer therapeutics, the mechanistic
      basis for their selectivity is not yet well understood. A high throughput screen
      for selective inhibitors of IDH1 bearing the oncogenic mutation R132H identified
      compound 1, a bis-imidazole phenol that inhibits d-2-hydroxyglutaric acid
      production in cells. We investigated the mode of inhibition of compound 1 and a
      previously published IDH1 mutant inhibitor with a different chemical scaffold.
      Steady-state kinetics and biophysical studies show that both of these compounds
      selectively inhibit mutant IDH1 by binding to an allosteric site and that
      inhibition is competitive with respect to Mg(2+). A crystal structure of compound
      1 complexed with R132H IDH1 indicates that the inhibitor binds at the dimer
      interface and makes direct contact with a residue involved in binding of the
      catalytically essential divalent cation. These results show that targeting a
      divalent cation binding residue can enable selective inhibition of mutant IDH1
      and suggest that differences in magnesium binding between wild-type and mutant
      enzymes may contribute to the inhibitors' selectivity for the mutant enzyme. 

PMID- 25391652
TI  - Role of apoptosis signal-regulating kinase 1 (ASK1) as an activator of the GAPDH
      Siah1 stress-signaling cascade.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays roles in both energy
      maintenance, and stress signaling by forming a protein complex with seven in
      absentia homolog 1 (Siah1). Mechanisms to coordinate its glycolytic and stress
      cascades are likely to be very important for survival and homeostatic control of
      any living organism. Here we report that apoptosis signal-regulating kinase 1
      (ASK1), a representative stress kinase, interacts with both GAPDH and Siah1 and
      is likely able to phosphorylate Siah1 at specific amino acid residues (Thr-70/Thr
      74 and Thr-235/Thr-239). Phosphorylation of Siah1 by ASK1 triggers GAPDH-Siah1
      stress signaling and activates a key downstream target, p300 acetyltransferase in
      the nucleus. This novel mechanism, together with the established S
      nitrosylation/oxidation of GAPDH at Cys-150, provides evidence of how the stress
      signaling involving GAPDH is finely regulated. In addition, the present results
      imply crosstalk between the ASK1 and GAPDH-Siah1 stress cascades. 

PMID- 25391654
TI  - Conformational dynamics of the focal adhesion targeting domain control specific
      functions of focal adhesion kinase in cells.
AB  - Focal adhesion (FA) kinase (FAK) regulates cell survival and motility by
      transducing signals from membrane receptors. The C-terminal FA targeting (FAT)
      domain of FAK fulfils multiple functions, including recruitment to FAs through
      paxillin binding. Phosphorylation of FAT on Tyr(925) facilitates FA disassembly
      and connects to the MAPK pathway through Grb2 association, but requires
      dissociation of the first helix (H1) of the four-helix bundle of FAT. We
      investigated the importance of H1 opening in cells by comparing the properties of
      FAK molecules containing wild-type or mutated FAT with impaired or facilitated H1
      openings. These mutations did not alter the activation of FAK, but selectively
      affected its cellular functions, including self-association, Tyr(925)
      phosphorylation, paxillin binding, and FA targeting and turnover. Phosphorylation
      of Tyr(861), located between the kinase and FAT domains, was also enhanced by the
      mutation that opened the FAT bundle. Similarly phosphorylation of Ser(910) by ERK
      in response to bombesin was increased by FAT opening. Although FAK molecules with
      the mutation favoring FAT opening were poorly recruited at FAs, they efficiently
      restored FA turnover and cell shape in FAK-deficient cells. In contrast, the
      mutation preventing H1 opening markedly impaired FAK function. Our data support
      the biological importance of conformational dynamics of the FAT domain and its
      functional interactions with other parts of the molecule. 

PMID- 25391655
TI  - Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5
      promotes angiogenesis and vasorelaxation.
AB  - Ginsenoside Rg5 is a compound newly synthesized during the steaming process of
      ginseng; however, its biological activity has not been elucidated with regard to
      endothelial function. We found that Rg5 stimulated in vitro angiogenesis of human
      endothelial cells, consistent with increased neovascularization and blood
      perfusion in a mouse hind limb ischemia model. Rg5 also evoked vasorelaxation in
      aortic rings isolated from wild type and high cholesterol-fed ApoE(-/-) mice but
      not from endothelial nitric-oxide synthase (eNOS) knock-out mice. Angiogenic
      activity of Rg5 was highly associated with a specific increase in insulin-like
      growth factor-1 receptor (IGF-1R) phosphorylation and subsequent activation of
      multiple angiogenic signals, including ERK, FAK, Akt/eNOS/NO, and Gi-mediated
      phospholipase C/Ca(2+)/eNOS dimerization pathways. The vasodilative activity of
      Rg5 was mediated by the eNOS/NO/cGMP axis. IGF-1R knockdown suppressed Rg5
      induced angiogenesis and vasorelaxation by inhibiting key angiogenic signaling
      and NO/cGMP pathways. In silico docking analysis showed that Rg5 bound with high
      affinity to IGF-1R at the same binding site of IGF. Rg5 blocked binding of IGF-1
      to its receptor with an IC50 of ~90 nmol/liter. However, Rg5 did not induce
      vascular inflammation and permeability. These data suggest that Rg5 plays a novel
      role as an IGF-1R agonist, promoting therapeutic angiogenesis and improving
      hypertension without adverse effects in the vasculature. 

PMID- 25391656
TI  - MicroRNA-200 is induced by thioredoxin-interacting protein and regulates Zeb1
      protein signaling and beta cell apoptosis.
AB  - Small noncoding microRNAs have emerged as important regulators of cellular
      processes, but their role in pancreatic beta cells has only started to be
      elucidated. Loss of pancreatic beta cells is a key factor in the pathogenesis of
      diabetes, and we have demonstrated that beta cell expression of thioredoxin
      interacting protein (TXNIP) is increased in diabetes and causes beta cell
      apoptosis, whereas TXNIP deficiency is protective against diabetes. Recently, we
      found that TXNIP also impairs beta cell function by inducing microRNA (miR)-204.
      Interestingly, using INS-1 beta cells and primary islets, we have now discovered
      that expression of another microRNA, miR-200, is induced by TXNIP and by
      diabetes. Furthermore, we found that miR-200 targeted and decreased Zeb1 (zinc
      finger E-box-binding homeobox 1) and promoted beta cell apoptosis as measured by
      cleaved caspase-3 levels, Bax/Bcl2 ratio, and TUNEL. In addition, Zeb1 knockdown
      mimicked the miR-200 effects on beta cell apoptosis, suggesting that Zeb1 plays
      an important role in mediating miR-200 effects. Moreover, miR-200 increased beta
      cell expression of the epithelial marker E-cadherin, consistent with inhibition
      of epithelial-mesenchymal transition, a process thought to be involved in beta
      cell expansion. Thus, we have identified a novel TXNIP/miR-200/Zeb1/E-cadherin
      signaling pathway that, for the first time, links miR-200 to beta cell apoptosis
      and diabetes and also beta cell TXNIP to epithelial-mesenchymal transition. In
      addition, our results shed new light on the regulation and function of miR-200 in
      beta cells and show that TXNIP-induced microRNAs control various processes of
      beta cell biology. 

PMID- 25391657
TI  - A splice variant of the human ion channel TRPM2 modulates neuroblastoma tumor
      growth through hypoxia-inducible factor (HIF)-1/2alpha.
AB  - The calcium-permeable ion channel TRPM2 is highly expressed in a number of
      cancers. In neuroblastoma, full-length TRPM2 (TRPM2-L) protected cells from
      moderate oxidative stress through increased levels of forkhead box transcription
      factor 3a (FOXO3a) and superoxide dismutase 2. Cells expressing the dominant
      negative short isoform (TRPM2-S) had reduced FOXO3a and superoxide dismutase 2
      levels, reduced calcium influx in response to oxidative stress, and enhanced
      reactive oxygen species, leading to decreased cell viability. Here, in xenografts
      generated with SH-SY5Y neuroblastoma cells stably expressing TRPM2 isoforms,
      growth of tumors expressing TRPM2-S was significantly reduced compared with
      tumors expressing TRPM2-L. Expression of hypoxia-inducible factor (HIF)-1/2alpha
      was significantly reduced in TRPM2-S-expressing tumor cells as was expression of
      target proteins regulated by HIF-1/2alpha including those involved in glycolysis
      (lactate dehydrogenase A and enolase 2), oxidant stress (FOXO3a), angiogenesis
      (VEGF), mitophagy and mitochondrial function (BNIP3 and NDUFA4L2), and
      mitochondrial electron transport chain activity (cytochrome oxidase 4.1/4.2 in
      complex IV). The reduction in HIF-1/2alpha was mediated through both
      significantly reduced HIF-1/2alpha mRNA levels and increased levels of von Hippel
      Lindau E3 ligase in TRPM2-S-expressing cells. Inhibition of TRPM2-L by
      pretreatment with clotrimazole or expression of TRPM2-S significantly increased
      sensitivity of cells to doxorubicin. Reduced survival of TRPM2-S-expressing cells
      after doxorubicin treatment was rescued by gain of HIF-1 or -2alpha function.
      These data suggest that TRPM2 activity is important for tumor growth and for cell
      viability and survival following doxorubicin treatment and that interference with
      TRPM2-L function may be a novel approach to reduce tumor growth through
      modulation of HIF-1/2alpha, mitochondrial function, and mitophagy. 

PMID- 25391660
TI  - Plasmodium falciparum mitochondria import tRNAs along with an active phenylalanyl
      tRNA synthetase.
AB  - The Plasmodium falciparum protein translation enzymes aminoacyl-tRNA synthetases
      (aaRSs) are an emergent family of drug targets. The aaRS ensemble catalyses
      transfer of amino acids to cognate tRNAs, thus providing charged tRNAs for
      ribosomal consumption. P. falciparum proteome expression relies on a total of 36
      aaRSs for the three translationally independent compartments of cytoplasm,
      apicoplast and mitochondria. In the present study, we show that, of this set of
      36, a single genomic copy of mitochondrial phenylalanyl-tRNA synthetase (mFRS) is
      targeted to the parasite mitochondria, and that the mFRS gene is exclusive to
      malaria parasites within the apicomplexan phyla. Our protein cellular
      localization studies based on immunofluorescence data show that, along with mFRS,
      P. falciparum harbours two more phenylalanyl-tRNA synthetase (FRS) assemblies
      that are localized to its apicoplast and cytoplasm. The 'extra' mFRS is found in
      mitochondria of all asexual blood stage parasites and is competent in
      aminoacylation. We show further that the parasite mitochondria import tRNAs from
      the cytoplasmic tRNA pool. Hence drug targeting of FRSs presents a unique
      opportunity to potentially stall protein production in all three parasite
      translational compartments. 

PMID- 25391658
TI  - Error-prone translesion synthesis past DNA-peptide cross-links conjugated to the
      major groove of DNA via C5 of thymidine.
AB  - DNA-protein cross-links (DPCs) are exceptionally bulky, structurally diverse DNA
      adducts formed in cells upon exposure to endogenous and exogenous bis
      electrophiles, reactive oxygen species, and ionizing radiation. If not repaired,
      DPCs can induce toxicity and mutations. It has been proposed that the protein
      component of a DPC is proteolytically degraded, giving rise to smaller DNA
      peptide conjugates, which can be subject to nucleotide excision repair and
      replication bypass. In this study, polymerase bypass of model DNA-peptide
      conjugates structurally analogous to the lesions induced by reactive oxygen
      species and DNA methyltransferase inhibitors was examined. DNA oligomers
      containing site-specific DNA-peptide conjugates were generated by copper
      catalyzed [3 + 2] Huisgen cyclo-addition between an alkyne-functionalized C5
      thymidine in DNA and an azide-containing 10-mer peptide. The resulting DNA
      peptide conjugates were subjected to steady-state kinetic experiments in the
      presence of recombinant human lesion bypass polymerases kappa and eta, followed
      by PAGE-based assays to determine the catalytic efficiency and the misinsertion
      frequency opposite the lesion. We found that human polymerase kappa and eta can
      incorporate A, G, C, or T opposite the C5-dT-conjugated DNA-peptide conjugates,
      whereas human polymerase eta preferentially inserts G opposite the lesion.
      Furthermore, HPLC-ESI(-)-MS/MS sequencing of the extension products has revealed
      that post-lesion synthesis was highly error-prone, resulting in mutations
      opposite the adducted site or at the +1 position from the adduct and multiple
      deletions. Collectively, our results indicate that replication bypass of peptides
      conjugated to the C5 position of thymine by human translesion synthesis
      polymerases leads to large numbers of base substitution and frameshift mutations.

PMID- 25391659
TI  - MEK1 transduces the prion protein N2 fragment antioxidant effects.
AB  - The prion protein (PrP(C)) when mis-folded is causally linked with a group of
      fatal neurodegenerative diseases called transmissible spongiform encephalopathies
      or prion diseases. PrP(C) normal function is still incompletely defined with such
      investigations complicated by PrP(C) post-translational modifications, such as
      internal cleavage, which feasibly could change, activate, or deactivate the
      function of this protein. Oxidative stress induces beta-cleavage and the N
      terminal product of this cleavage event, N2, demonstrates a cellular protective
      response against oxidative stress. The mechanisms by which N2 mediates cellular
      antioxidant protection were investigated within an in vitro cell model. N2
      protection was regulated by copper binding to the octarepeat domain, directing
      the route of internalisation, which stimulated MEK1 signalling. Precise membrane
      interactions of N2, determined by copper saturation, and involving both the
      copper-co-ordinating octarepeat region and the structure conferred upon the N
      terminal polybasic region by the proline motif, were essential for the correct
      engagement of this pathway. The phenomenon of PrP(C) post-translational
      modification, such as cleavage and copper co-ordination, as a molecular "switch"
      for activation or deactivation of certain functions provides new insight into the
      apparent multi-functionality of PrP(C). 

PMID- 25391661
TI  - Conditions, components and outcomes of Integrative Validation Therapy in a long
      term care facility for people with dementia. A qualitative evaluation study.
AB  - In this study, the practical application of Integrative Validation Therapy (IVA)
      in a nursing home for people with dementia was investigated and evaluated from
      the perspectives of professionals and relatives by using Fourth Generation
      Evaluation. IVA, a complex intervention frequently applied in Germany's long-term
      care settings, is a modification of Feil's Validation Therapy and contains a
      specific attitude and several components of action. The findings demonstrate that
      professionals as well as relatives of nursing home residents gave the
      intervention a positive rating. From the perspective of the participating
      professionals, the application of IVA results in less agitated residents which
      also has an influence on the consumption of benzodiazepine and neuroleptics. The
      authors conclude that IVA is a beneficial nursing intervention helping to
      facilitate the illness-related transition process of people with dementia. IVA is
      able to support them to cope with emotional distress during transition (e.g.
      irritability, anxiety, depression, changes in self-esteem). Another conclusion is
      that IVA supports person-centred care because, with IVA, professionals react to
      typical needs people with dementia have: comfort, inclusion, attachment and
      identity (Kitwood, 2012). 

PMID- 25391663
TI  - Longitudinal muscle gene expression patterns associated with differential
      intramuscular fat in cattle.
AB  - Intramuscular fat (IMF) can improve meat product quality through its impact on
      flavour and juiciness. High marbling cuts can command premium prices in some
      countries and grading systems, but there is substantial cost involved in choosing
      to grain feed animals in an effort to deposit more IMF. There would be value in
      developing methods to predict predisposition to 'marble' well. Unfortunately, the
      biological mechanisms underpinning marbling remain a mystery: the key adipocyte
      cell populations have not been defined, there are no reliable DNA markers, no
      known (if any) causal mutations and gene expression analyses in the main have
      tended to characterise increases in expression of end-point fat metabolism
      proteins such as the fatty acid-binding proteins. To shed light on expression
      based markers of marbling potential, we contrasted LD gene expression in high IMF
      Wagyu cross animals with a low IMF Piedmontese cross at various time points. The
      expected divergence in the fat metabolism genes FABP4, THRSP, CIDEC and ACACA
      between the breeds occurs surprisingly late in postnatal development at about 20
      months. On the other hand, divergent expression of WISP2, RAI14 and CYP4F2 was
      discovered in animals at or before 12 months of age, suggesting these genes may
      have potential as earlier predictors of marbling potential. In line with other
      researchers, we found intriguing links between IMF development and connective
      tissue remodelling. WISP2 - a novel adipokine highly expressed and secreted by
      adipose precursor cells and an inhibitor of the pro-fibrotic connective tissue
      growth factor - emerges as a particularly attractive candidate. It is relatively
      upregulated in high marbling Wagyu before admission to feedlotting, somewhere
      between 7 and 12 months. This difference is subsequently maintained until 25
      months, but not thereafter. RAI14, thought to play a role in porcine adipocyte
      differentiation and with links to retinoic acid metabolism, has an unusual
      expression profile. Its expression level increases monotonically with postnatal
      development, and is always higher in Wagyu than Piedmontese. Strong, sustained
      upregulation of the anti-inflammatory CYP4F2 in Piedmontese is consistent with
      Wagyu adiposity being a pro-inflammatory state. Application of regulatory impact
      factor analysis, a network method for identifying causal effector molecules,
      suggests marbling roles for transcription factors previously implicated in (1)
      the formation of liposarcoma (unconstrained fatty masses) (YEATS4, MDM2), (2)
      adipogenesis (CREBL2, SP1, STAT1) and (3) inflammation (ISGF3G, HOXB13, PML). 

PMID- 25391664
TI  - Bullying among radiation therapists: effects on job performance and work
      environment.
AB  - PURPOSE: To identify the effects of workplace bullying in the radiation therapy
      department on job performance and explore the environment and morale of
      individuals who work with a bully. METHODS: A quantitative research study was
      designed to assess the prevalence and effects of bullying in the radiation
      therapy workplace. RESULTS: A total of 308 radiation therapists participated in
      the study for a return rate of 46%. Of those, 194 indicated that workplace
      bullying was present either in their current workplace or in a previous radiation
      therapy environment and that it negatively affected job performance and
      satisfaction. DISCUSSION: Findings of this study indicate a need for evaluation
      of the radiation therapy workplace, education on how to identify and prevent
      bullying behavior, and better communication among members of the radiation
      therapy environment. Participants indicated that working in a hostile environment
      led to forgetfulness, ineffective communication, and perceived discrepancies in
      promotion and treatment by management. CONCLUSION: Any bullying behavior
      contributes to an overall toxic work environment, which is unhealthy and unsafe
      for patients and therapists. Those who manage therapists should promote a culture
      of safety and embrace their staff's independence.

PMID- 25391662
TI  - TDP-1, the Caenorhabditis elegans ortholog of TDP-43, limits the accumulation of
      double-stranded RNA.
AB  - Caenorhabditis elegans mutants deleted for TDP-1, an ortholog of the
      neurodegeneration-associated RNA-binding protein TDP-43, display only mild
      phenotypes. Nevertheless, transcriptome sequencing revealed that many RNAs were
      altered in accumulation and/or processing in the mutant. Analysis of these
      transcriptional abnormalities demonstrates that a primary function of TDP-1 is to
      limit formation or stability of double-stranded RNA. Specifically, we found that
      deletion of tdp-1: (1) preferentially alters the accumulation of RNAs with
      inherent double-stranded structure (dsRNA); (2) increases the accumulation of
      nuclear dsRNA foci; (3) enhances the frequency of adenosine-to-inosine RNA
      editing; and (4) dramatically increases the amount of transcripts
      immunoprecipitable with a dsRNA-specific antibody, including intronic sequences,
      RNAs with antisense overlap to another transcript, and transposons. We also show
      that TDP-43 knockdown in human cells results in accumulation of dsRNA, indicating
      that suppression of dsRNA is a conserved function of TDP-43 in mammals. Altered
      accumulation of structured RNA may account for some of the previously described
      molecular phenotypes (e.g., altered splicing) resulting from reduction of TDP-43
      function.

PMID- 25391665
TI  - Radiologic science students' perceptions of parental involvement.
AB  - BACKGROUND: A new generation of students is in the classroom, and they are not
      always alone. Helicopter parents, those who hover around the student and attempt
      to ease life's challenges, are accompanying the students to radiologic science
      programs across the nation. PURPOSE: To determine radiologic science students'
      perception regarding their parents' level of involvement in their lives. METHODS:
      A survey focused on student perceptions of parental involvement inside and
      outside of the academic setting was completed by 121 radiologic science students
      at 4 institutional settings. RESULTS: The analysis demonstrates statistically
      significant relationships between student sex, age, marital status, and perceived
      level of parental involvement. In addition, as financial support increases,
      students' perception of the level of parental involvement also increases.
      DISCUSSION: Radiologic science students want their parents to be involved in
      their higher education decisions. Research indicates that students with involved
      parents are more successful, and faculty should be prepared for increased
      parental involvement in the future. CONCLUSION: Radiologic science students
      perceive their parents to be involved in their academic careers. Ninety-five
      percent of respondents believe that the financial support of their parent or
      parents contributes to their academic success. Sixty-five percent of participants
      are content with their parents' current level of involvement, while 11% wish
      their parents were more involved in their academic careers.

PMID- 25391666
TI  - Smart device use and burnout among health science educators.
AB  - PURPOSE: This study examines the perceived level of stress and burnout among
      health science educators related to smart device use. METHODS: An
      interdisciplinary health science research team was created to perform a
      literature review and design a survey and assessment instrument to investigate
      the level of stress and burnout among health science educators as a result of
      excessive connectivity to the workplace through smart device use. A total of 977
      assessments were completed through distribution by program directors in athletic
      training, nursing, radiologic sciences, and respiratory care. RESULTS:
      Participants in the study, who represented program directors and educators in the
      allied health sciences, reported 70% of their smart device use taking place
      between the hours of 6 am and 6 pm, followed by 30% between 6 pm and 12 am.
      Slightly more than 60% of participants reported feeling connected to the
      workplace at all hours of the day. Emotional exhaustion and personal
      accomplishment scores for participants were stronger than the norm as measured by
      the Maslach Burnout Inventory. DISCUSSION: There appears to be a strong feeling
      of connectedness to the workplace caused by the use of smart devices (60.7%).
      Some surveyed educators appear to manage their smart device use better than
      others because 55% of participants indicated they sometimes ignore work-related
      items after hours. Although several participants demonstrated physical signs of
      stress and burnout, a causal relationship between use of smart devices or work
      connectedness could not be established. CONCLUSION: Based on the findings of this
      study, the null hypothesis was rejected. Significant levels of emotional
      exhaustion were seen in a subset of study participants. Our findings indicate
      that emotional exhaustion occurs when healthy boundaries are not maintained for
      smart device use for work purposes after hours.

PMID- 25391667
TI  - Gene therapy review.
AB  - The use of genes to treat disease, more commonly known as gene therapy, is a
      valid and promising tool to manage and treat diseases that conventional drug
      therapies cannot cure. Gene therapy holds the potential to control a wide range
      of diseases, including cystic fibrosis, heart disease, diabetes, cancer, and
      blood diseases. This review assesses the current status of gene therapy,
      highlighting therapeutic methodologies and applications, terminology, and imaging
      strategies. This article presents an overview of roadblocks associated with each
      therapeutic methodology, along with some of the scientific, social, and ethical
      issues associated with gene therapy. 

PMID- 25391668
TI  - Pretransfer imaging decisions in rural trauma cases.
AB  - In rural health settings, patients with trauma who initially are transported to a
      community hospital often require transfer to a designated trauma center. Rural
      hospitals typically are not equipped or properly staffed to treat severely
      injured patients. When trauma occurs, transport time longer than 60 minutes from
      an accident scene to a place of definitive care can have detrimental effects on
      the patient. This article discusses the differences in trauma care in rural and
      urban settings, explains situations in which the patient might not benefit from
      diagnostic imaging before transfer to an urban facility, and outlines ways to
      reduce unnecessary imaging of trauma patients at rural locations. 

PMID- 25391669
TI  - Innovations shared at radiation therapy conference.

PMID- 25391670
TI  - A case of cystic fibrosis.

PMID- 25391671
TI  - The central role of practice analysis in certification.

PMID- 25391672
TI  - Is fear of rejection standing in the way of publication?

PMID- 25391673
TI  - Philosophy of leadership in radiology education.

PMID- 25391674
TI  - Influenza vaccination for health care personnel.

PMID- 25391675
TI  - Reporting program effectiveness data.

PMID- 25391680
TI  - CT image visualization: a conceptual introduction.
AB  - Computed tomography (CT) postprocessing produces information-rich diagnostic
      images, transforming enormous amounts of x-ray attenuation data into clinical
      information that can assist in diagnosis and treatment. This article briefly
      reviews the history of the technological evolution of CT imaging equipment and
      provides a conceptual overview of scan data visualization processes. Trends in
      and examples of image postprocessing, segmentation, registration and fusion
      techniques, and computer-aided detection are described. Finally, the uses of
      these visualization algorithms in selected diagnostic imaging applications are
      discussed. 

PMID- 25391681
TI  - Predicting Liver Transplant Capacity Using Discrete Event Simulation.
AB  - The number of liver transplants (LTs) performed in the US increased until 2006
      but has since declined despite an ongoing increase in demand. This decline may be
      due in part to decreased donor liver quality and increasing discard of poor
      quality livers. We constructed a discrete event simulation (DES) model informed
      by current donor characteristics to predict future LT trends through the year
      2030. The data source for our model is the United Network for Organ Sharing
      database, which contains patient-level information on all organ transplants
      performed in the US. Previous analysis showed that liver discard is increasing
      and that discarded organs are more often from donors who are older, are obese,
      have diabetes, and donated after cardiac death. Given that the prevalence of
      these factors is increasing, the DES model quantifies the reduction in the number
      of LTs performed through 2030. In addition, the model estimatesthe total number
      of future donors needed to maintain the current volume of LTs and the effect of a
      hypothetical scenario of improved reperfusion technology.We also forecast the
      number of patients on the waiting list and compare this with the estimated number
      of LTs to illustrate the impact that decreased LTs will have on patients needing
      transplants. By altering assumptions about the future donor pool, this model can
      be used to develop policy interventions to prevent a further decline in this
      lifesaving therapy. To our knowledge, there are no similar predictive models of
      future LT use based on epidemiological trends.

PMID- 25391682
TI  - MPs demand action on "significant" conflicts of interest in GP out-of-hours care.

PMID- 25391683
TI  - Effects of rice bran protein hydrolysates on the physicochemical stability of oil
      in-water emulsions.
AB  - Isolation of proteins from rice bran was studied, comparing alkaline- and
      carbohydrase-aided extraction. It was found that protein extractability could be
      effectively improved using carbohydrases (Viscozyme L and alpha-amylase),
      especially when mechanical force was incorporated. Then, rice bran protein
      hydrolysates (RBPH) were prepared at various degrees of hydrolysis (DH), and
      employed to stabilize soybean O/W emulsion. Improved colloidal stability of the
      emulsions could be achieved using RBPH, especially at higher DH level, as
      indicated by an increase in the emulsifying activity index and better long-term
      dispersibility. The present work novelty suggested the efficiency of RBPH to
      improve oxidative stability of the emulsions. The most potent antioxidant
      activity was exhibited by RBPH with DH of 6.4 and 7.6%. With their efficiency to
      promote physicochemical stability of the emulsions, RBPH might be potently
      employed as a natural additive in emulsified food products, which is significant
      to value addition of rice bran for further industrial application. 

PMID- 25391684
TI  - Determination of carbon isotopic measurement conditions for ceramide in skin
      using gas chromatography-combustion-isotope ratio mass spectrometry.
AB  - The ceramide (Cer) content of skin and glucosylceramide (GlcCer) intake affect
      skin moisture conditions, but their mutual relation in skin remains unclear. For
      clarification of that mutual relation, carbon stable isotopes ((12)C and (13)C)
      are useful as a tracer. However, carbon isotopic measurement has not been applied
      to the study of clarifying their skin moisturizing effects. Therefore, we used
      gas chromatography / combustion / isotope ratio mass spectrometry (GC-C-IRMS) to
      ascertain the appropriate conditions for carbon isotopic measurements using
      synthesized Cer (SCer) in substitution for very low concentrations of Cer in
      skin. SCer was derivatized to trimethylsilylated SCer (TMS-SCer) quantitatively
      using N-trimethylsilylimidazole (TMSI) depending on the amount of SCer. The
      derivatization rates were 75-85%. Excess TMSI was removed using three cycles of
      hexane-water distribution. Under these conditions, carbon isotopic measurements
      of TMS-SCer conducted using GC-C-IRMS showed high repeatability and good inter
      day variation (S.D. < 0.30/00). The carbon stable isotope ratio value
      (delta(13)C) of SCer calculated using a mass balance equation was compared with
      delta(13)C of underivatized SCer, which was regarded as the actual delta(13)C of
      SCer obtained using sealed tube combustion method. The difference between the
      calculated delta(13)C of SCer and delta(13)C of the underivatized SCer depended
      on the TMSI reagent supplier and on the number of hydroxyl groups to be
      derivatized in SCer. For accurate delta(13)C of Cer in skin using GC-C-IRMS, the
      measured delta(13)C of a target TMS-Cer must be calculated using a correction
      factor representing the difference in delta(13)C of underivatized standard SCer
      from that of TMS-standard SCer having a structure resembling that of the target
      Cer in skin. In addition, we show that the same lot of TMSI reagent from a
      specific supplier must be used throughout the experiments. 

PMID- 25391685
TI  - Chemical characterization and antioxidant activity of Amazonian (Ecuador)
      Caryodendron orinocense Karst. and Bactris gasipaes Kunth seed oils.
AB  - Nowadays, data concerning the composition of Caryodendron orinocense Karst.
      (Euphorbiaceae) and Bactris gasipaes Kunth (Arecaceae) seed oils are lacking. In
      light of this fact, in this paper fatty acids and unsaponifiable fraction
      composition have been determined using GC-MS, HPLC-DAD (Diode Array Detector),
      NMR approaches and possible future applications have been preliminary
      investigated through estimation of antioxidant activity, performed with DPPH
      test. For C. orinocense linoleic acid (85.59%) was the main component, lauric
      (33.29%) and myristic (27.76%) acids were instead the most abundant in B.
      gasipaes. C. orinocense unsaponifiable fraction (8.06%) evidenced a remarkable
      content of beta-sitosterol, campesterol, stigmasterol, squalene and vitamin E
      (816 ppm). B. gasipaes revealed instead beta-sitosterol and squalene as main
      constituents of unsaponifiable matter (3.01%). Antioxidant capacity evidenced the
      best performance of C. orinocense seed oil. These preliminary results could be
      interesting to suggest the improvement of the population's incomes from Amazonian
      basin. In particular the knowledge of chemical composition of C. orinocense and
      B. gasipaes oils could be helpful to divulge and valorize these autochthones
      plants. 

PMID- 25391686
TI  - Impact of different deacidification methods on quality characteristics and
      composition of olein and stearin in crude red palm oil.
AB  - Crude red palm oil of 8.7% free fatty acid content was deacidified using enzyme
      (lipase from Rhizomucor miehei), solvent (ethanol) and chemical (aqueous Sodium
      hydroxide) and its impact on chemical characteristics and composition were
      evaluated. Deacidification of oil using enzyme showed nearly 100% product yield.
      The neutral lipid loss after ethanol and sodium hydroxide deacidification of the
      oil was 13.6% and 19.5% respectively. The enzyme deacidified oil has shown a
      higher value in unsaponifiable matter (0.91%), monoacylglycerols (2.8%) and
      diacylglycerols (18.7%) contents as compared to the other two methods of
      deacidification. Also it showed a higher retention of nutraceuticals such as
      carotenoids (94%), phytosterols (57%), total tocopherols (71%), squalene (72%),
      coenzyme Q10 (99%) and total phenolics (69%) with IC50 value of 19.7 mg of
      oil/ml. Stearin content increased in the oil after deacidification with enzyme
      (47.4%) compared to the stearin content of crude red palm oil (28.6%). The olein
      fraction contained less saturated fatty acids (41.6%) than the fraction obtained
      by other two methods (47.2%). The enzyme catalyzed the esterification reaction of
      free fatty acids in crude red palm oil with added glycerol at 63 degrees C with a
      rotation speed of 150 rpm under vacuum of 5 mmHg for the period of 12 h showed
      that enzyme based deacidification can be effectively utilized for the preparation
      of low acidic nutraceutical retained red palm oil. 

PMID- 25391687
TI  - Purification and physicochemical properties of lipase from thermophilic Bacillus
      aerius.
AB  - A thermophilic bacterial isolate producing lipase was isolated from soil of hot
      spring and identified as Bacillus aerius (MTCC 10978). Peak lipase activity was
      observed when 30 h old inoculum was used and incubated in shaking conditions for
      48 h. The optimal temperature and pH for the bacterial growth and lipase
      production was found to be 55 degrees C and 8.0 respectively with cottonseed oil
      as carbon source, yeast extract and beef extract as nitrogen source. The enzyme
      produced by thermophilic Bacillus aerius (MTCC 10978) was purified to 9-fold with
      7.2% recovery by ammonium sulfate precipitation and DEAE-Cellulose Column
      Chromatography. The enzyme was found to be a protein having a molecular weight of
      33 kDa on SDS-PAGE. The Km and Vmax value of lipase using p-nitrophenyl palmitate
      as calculated from Lineweaver-Burk plot was 2.13 mM and 0.66 umol/ml/min
      respectively. 

PMID- 25391688
TI  - More is more in remote Central Australia: more provision of primary healthcare
      services is associated with more acute medical evacuations and more remote
      telephone consultations.
AB  - INTRODUCTION: This study investigated whether increased numbers of primary
      healthcare clinical consultations in Indigenous communities in some remote areas
      of Australia are associated with the reduced need for urgent medical evacuations
      and remote telephone consultations. METHODS: A retrospective comparison study of
      routinely collected data utilising correlation analysis was conducted.
      Statistical associations have been measured using Pearson product-moment
      correlation coefficients. The setting was 20 primary healthcare centres in the
      Northern Territory servicing >=5900 residents between July 2008 and June 2010;
      data were collected from Central Australia Remote Health and the Royal Flying
      Doctor Service-Central Operations, Alice Springs base. Main outcome measures
      included number of acute medical evacuations and number of remote telephone
      consultations relative to number of face-to-face consultations with Aboriginal
      health workers, remote area nurses and general practitioners. RESULTS:
      Statistically significant positive correlations were found between numbers of
      acute medical evacuations and numbers of face-to-face consultations (r = 0.659;
      95% confidence interval (CI): 0.305-0.855), remote area nurse consultations (r =
      0.481; 95% CI: 0.055-0.765) and general practitioner consultations (r = 0.798;
      95% CI: 0.555-0.920). Significant positive correlations were also found between
      numbers of remote telephone consultations and numbers of face-to-face
      consultations (r = 0.546; 95% CI: 0.135-0.795) and general practitioner
      consultations (r = 0.563; 95% CI: 0.163-0.805). CONCLUSIONS: The provision of
      more frequent healthcare centre face-to-face consultations, including general
      practitioner consultations, is associated with an increased burden of acute
      medical evacuations and remote telephone consultation services in this remote
      setting.

PMID- 25391689
TI  - Responses of gas-exchange rates and water relations to annual fluctuations of
      weather in three species of urban street trees.
AB  - The frequency of extreme weather has been rising in recent years. A 3-year study
      of street trees was undertaken in Tokyo to determine whether: (i) street trees
      suffer from severe water stress in unusually hot summer; (ii) species respond
      differently to such climatic fluctuations; and (iii) street trees are also
      affected by nitrogen (N) deficiency, photoinhibition and aerosol pollution.
      During the study period (2010-12), midsummers of 2010 and 2012 were unusually hot
      (2.4-2.8  degrees C higher maximum temperature than the long-term mean) and dry
      (6-56% precipitation of the mean). In all species, street trees exhibited
      substantially decreased photosynthetic rate in the extremely hot summer in 2012
      compared with the average summer in 2011. However, because of a more conservative
      stomatal regulation (stomatal closure at higher leaf water potential) in the hot
      summer, apparent symptoms of hydraulic failure were not observed in street trees
      even in 2012. Compared with Prunus * yedoensis and Zelkova serrata, Ginkgo
      biloba, a gymnosperm, was high in stomatal conductance and midday leaf water
      potential even under street conditions in the unusually hot summer, suggesting
      that the species had higher drought resistance than the other species and was
      less susceptible to urban street conditions. This lower susceptibility might be
      ascribed to the combination of higher soil-to-leaf hydraulic conductance and more
      conservative water use. Aside from meteorological conditions, N deficiency
      affected street trees significantly, whereas photoinhibition and aerosol
      pollution had little effect. The internal CO2 and delta(13)C suggested that both
      water and N limited the net photosynthetic rate of street trees simultaneously,
      but water was more limiting. From these results, we concluded that the potential
      risk of hydraulic failure caused by climatic extremes could be low in urban
      street trees in temperate regions. However, the size of the safety margin might
      be different between species. 

PMID- 25391690
TI  - Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a
      translational research immunotherapy paradigm.
AB  - Glioblastomas are primary intracranial tumors for which there is no cure.
      Patients receiving standard of care, chemotherapy and irradiation, survive
      approximately 15 months prompting studies of alternative therapies including
      vaccination. In a pilot study, a vaccine consisting of Lucite diffusion chambers
      containing irradiated autologous tumor cells pre-treated with an antisense
      oligodeoxynucleotide (AS-ODN) directed against the insulin-like growth factor
      type 1 receptor was found to elicit positive clinical responses in 8/12 patients
      when implanted in the rectus sheath for 24 h. Our preliminary observations
      supported an immune response, and we have since reopened a second Phase 1 trial
      to assess this possibility among other exploratory objectives. The current study
      makes use of a murine glioma model and samples from glioblastoma patients in this
      second Phase 1 trial to investigate this novel therapeutic intervention more
      thoroughly. Implantation of the chamber-based vaccine protected mice from tumor
      challenge, and we posit this occurred through the release of immunostimulatory AS
      ODN and antigen-bearing exosomes. Exosomes secreted by glioblastoma cultures are
      immunogenic, eliciting and binding antibodies present in the sera of immunized
      mice. Similarly, exosomes released by human glioblastoma cells bear antigens
      recognized by the sera of 6/12 patients with recurrent glioblastomas. These
      results suggest that the release of AS-ODN together with selective release of
      exosomes from glioblastoma cells implanted in chambers may drive the therapeutic
      effect seen in the pilot vaccine trial.

PMID- 25391691
TI  - Provider cost analysis supports results-based contracting out of maternal and
      newborn health services: an evidence-based policy perspective.
AB  - BACKGROUND: There is dearth of evidence on provider cost of contracted out
      services particularly for Maternal and Newborn Health (MNH). The evidence base is
      weak for policy makers to estimate resources required for scaling up contracting.
      This paper ascertains provider unit costs and expenditure distribution at
      contracted out government primary health centers to inform the development of
      optimal resource envelopes for contracting out MNH services. METHODS: This is a
      case study of provider costs of MNH services at two government Rural Health
      Centers (RHCs) contracted out to a non-governmental organization in Pakistan. It
      reports on four selected Basic Emergency Obstetrical and Newborn Care (BEmONC)
      services provided in one RHC and six Comprehensive Emergency Obstetrical and
      Newborn Care (CEmONC) services in the other. Data were collected using staff
      interviews and record review to compile resource inputs and service volumes, and
      analyzed using the CORE Plus tool. Unit costs are based on actual costs of MNH
      services and are calculated for actual volumes in 2011 and for volumes projected
      to meet need with optimal resource inputs. RESULTS: The unit costs per service
      for actual 2011 volumes at the BEmONC RHC were antenatal care (ANC) visit USD$
      18.78, normal delivery US$ 84.61, newborn care US$ 16.86 and a postnatal care
      (PNC) visit US$ 13.86; and at the CEmONC RHC were ANC visit US$ 45.50, Normal
      Delivery US$ 148.43, assisted delivery US$ 167.43, C-section US$ 183.34, Newborn
      Care US$ 41.07, and PNC visit US$ 27.34. The unit costs for the projected volumes
      needed were lower due to optimal utilization of resources. The percentage
      distribution of expenditures at both RHCs was largest for salaries of technical
      staff, followed by salaries of administrative staff, and then operating costs,
      medicines, medical and diagnostic supplies. CONCLUSIONS: The unit costs of MNH
      services at the two contracted out government rural facilities remain higher than
      is optimal, primarily due to underutilization. Provider cost analysis using
      standard treatment guideline (STG) based service costing frameworks should be
      applied across a number of health facilities to calculate the cost of services
      and guide development of evidence based resource envelopes and performance based
      contracting.

PMID- 25391692
TI  - The use of FAST scan by paramedics in mass-casualty incidents: a simulation
      study.
AB  - INTRODUCTION: The Focused Abdominal Sonography in Trauma (FAST) scan is used to
      detect free fluid in the peritoneal cavity, or pericardium, to quickly assess for
      injuries needing immediate surgical intervention. Mass-casualty incidents (MCIs)
      are settings where paramedics must make triage decisions in minutes. The Simple
      Triage and Rapid Transport (START) system is used to prioritize transport. The
      FAST scan can be added to the triage of critical patients, and may aid in triage.
      METHODS: This was a single-blinded, randomized control trial. Ten paramedics with
      field experience were trained with an ultrasound machine in the performance of
      the FAST scan. Two weeks were allowed to pass before testing to simulate the time
      between training of standard procedures and their implementation. On test day,
      five peritoneal dialysis patients with instilled dialysis fluid and five matched
      control patients were placed in a room in a random order where the paramedics
      performed FAST scans on each patient. The paramedics were assessed by declaring
      positive or negative for each evaluation, as well as being timed for the total
      exercise. RESULTS: Of the ninety tests (one paramedic dropped out due to family
      emergency), the paramedics had a mean accuracy of 60% and median of 62% (range
      40%-80%). There was a statistically significant higher false-positive rate of 59%
      than false-negative rate of 41% (P < .01). Sensitivity was 67% with a specificity
      of 56%. Average time taken was 1,218 seconds (121.8 seconds per patient) with a
      range of 735-1,701 seconds and a median of 1,108 seconds. CONCLUSION: In this
      simulation study, paramedics had difficulty performing FAST scans with a high
      degree of accuracy. However, they were more apt to call a patient positive,
      limiting the likelihood for false-negative triage.

PMID- 25391694
TI  - Factors affecting medication adherence: patient perspectives from five veterans
      affairs facilities.
AB  - BACKGROUND: In the United States, more than 25 million people have diabetes.
      Medication adherence is known to be important for disease control. However,
      factors that consistently predict medication adherence are unclear and the
      literature lacks patient perspectives on how health care systems affect adherence
      to oral hypoglycemic agents (OHAs). This study explored facilitators and barriers
      to OHA adherence by obtaining the perspectives of Veterans Affairs (VA) patients
      with OHA prescriptions. METHODS: A total of 45 patients participated in 12 focus
      groups that explored a wide range of issues that might affect medication
      adherence. Participants were patients at clinics in Seattle, Washington; San
      Antonio, Texas; Portland, Oregon; Salem, Oregon, and Warrenton, Oregon. RESULTS:
      Key system-level facilitators of OHA adherence included good overall pharmacy
      service and several specific mechanisms for ordering and delivering medications
      (automated phone refill service, Web-based prescription ordering), as well as
      providing pillboxes and printed lists of current medications to patients.
      Barriers mirrored many of the facilitators. Poor pharmacy service quality and
      difficulty coordinating multiple prescriptions emerged as key barriers.
      CONCLUSIONS: VA patient focus groups provided insights on how care delivery
      systems can encourage diabetes medication adherence by minimizing the barriers
      and enhancing the facilitators at both the patient and system levels. Major
      system-level factors that facilitated adherence were overall pharmacy service
      quality, availability of multiple systems for reordering medications, having a
      person to call when questions arose, counseling about the importance of adherence
      and providing tools such as pillboxes and updated medication lists.

PMID- 25391693
TI  - The role of the LRRK2 gene in Parkinsonism.
AB  - Parkinson's disease (PD), like many common age-related conditions, has been
      recognized to have a substantial genetic component. Multiple lines of evidence
      suggest that Leucine-rich repeat kinase 2 (LRRK2) is a crucial factor to
      understanding the etiology of PD. LRRK2 is a large, widely expressed, multi
      domain and multifunctional protein. LRRK2 mutations are the major cause to
      inherited and sporadic PD. In this review, we discuss the pathology and clinical
      features which show diversity and variability of LRRK2-associated PD. In
      addition, we do a thorough literature review and provide theoretical data for
      gene counseling. Further, we present the evidence linking LRRK2 to various
      possible pathogenic mechanism of PD such as alpha-synuclein, tau, inflammatory
      response, oxidative stress, mitochondrial dysfunction, synaptic dysfunction as
      well as autophagy-lysosomal system. Based on the above work, we investigate
      activities both within GTPase and outside enzymatic regions in order to obtain a
      potential therapeutic approach to solve the LRRK2 problem. 

PMID- 25391695
TI  - Phase II clinical trial of multiple peptide vaccination for advanced head and
      neck cancer patients revealed induction of immune responses and improved OS.
AB  - PURPOSE: The peptides derived from ideal cancer-testis antigens, including LY6K,
      CDCA1, and IMP3 (identified using genome-wide cDNA microarray analyses), were
      used in immunotherapy for head and neck squamous cell cancer (HNSCC). In this
      trial, we analyzed the immune response to and safety and efficacy of vaccine
      therapy. EXPERIMENTAL DESIGN: A total of 37 patients with advanced HNSCC were
      enrolled in this trial of peptide vaccine therapy, and the OS, PFS, and
      immunologic response were evaluated using enzyme-linked ImmunoSpot (ELISPOT) and
      pentamer assays. The peptides were subcutaneously administered weekly with IFA.
      The primary endpoints were evaluated on the basis of differences between HLA
      A*2402-positive [A24(+)] patients treated with peptide vaccine therapy and 
      negative [A24(-)] patients treated without peptide vaccine therapy among those
      with advanced HNSCC. RESULTS: Our cancer vaccine therapy was well tolerated. The
      OS of the A24(+) vaccinated group (n = 37) was statistically significantly longer
      than that of the A24(-) group (n = 18) and median survival time (MST) was 4.9
      versus 3.5 months, respectively; P < 0.05. One of the patients exhibited a
      complete response. In the A24(+) vaccinated group, the ELISPOT assay identified
      LY6K-, CDCA1-, and IMP3-specific CTL responses in 85.7%, 64.3%, and 42.9% of the
      patients, respectively. The patients showing LY6K- and CDCA1-specific CTL
      responses demonstrated a longer OS than those without CTL induction. Moreover,
      the patients exhibiting CTL induction for multiple peptides demonstrated better
      clinical responses. CONCLUSIONS: The immune response induced by this vaccine may
      improve the prognosis of patients with advanced HNSCC.

PMID- 25391696
TI  - Safety and efficacy of VCN-01, an oncolytic adenovirus combining fiber HSG
      binding domain replacement with RGD and hyaluronidase expression.
AB  - PURPOSE: Tumor targeting upon intravenous administration and subsequent
      intratumoral virus dissemination are key features to improve oncolytic adenovirus
      therapy. VCN-01 is a novel oncolytic adenovirus that combines selective
      replication conditional to pRB pathway deregulation, replacement of the heparan
      sulfate glycosaminoglycan putative-binding site KKTK of the fiber shaft with an
      integrin-binding motif RGDK for tumor targeting, and expression of hyaluronidase
      to degrade the extracellular matrix. In this study, we evaluate the safety and
      efficacy profile of this novel oncolytic adenovirus. EXPERIMENTAL DESIGN: VCN-01
      replication and potency were assessed in a panel of tumor cell lines. VCN-01
      tumor-selective replication was evaluated in human fibroblasts and pancreatic
      islets. Preclinical toxicity, biodistribution, and efficacy studies were
      conducted in mice and Syrian hamsters. RESULTS: Toxicity and biodistribution
      preclinical studies support the selectivity and safety of VCN-01. Antitumor
      activity after intravenous or intratumoral administration of the virus was
      observed in all tumor models tested, including melanoma and pancreatic
      adenocarcinoma, both in immunodeficient mice and immunocompetent hamsters.
      CONCLUSIONS: Oncolytic adenovirus VCN-01 characterized by the expression of
      hyaluronidase and the RGD shaft retargeting ligand shows an efficacy-toxicity
      prolife in mice and hamsters by intravenous and intratumoral administration that
      warrants clinical testing.

PMID- 25391697
TI  - A concept of a nonneuronal cardiac cholinergic system.

PMID- 25391698
TI  - Catheter-retaining balloon-occluded retrograde transvenous obliteration for
      gastric varices.
AB  - PURPOSE: We evaluated the effectiveness of catheter-retaining balloon-occluded
      retrograde transvenous obliteration (BRTO). PATIENTS AND METHODS: Patients were
      divided into 2 groups based on concurrent contrast imaging findings. The primary
      endpoint was effectiveness, the secondary endpoint was complications, and the
      tertiary endpoint was recurrence of esophageal varices in all cases. RESULTS: The
      mean volume of EO administered was 16.43 +/- 4.37 overall and was significantly
      lower in group 1 (40.61 +/- 14.95 mL; 15 patients, 32.6%) than in group 2 (31
      patients, 67.4%). The number of injections was 1.60 +/- 0.63 in group 1 and 2.97
      +/- 0.60 in group 2, and the volume of EO used in 1 day did not differ
      significantly between group 1 (12.28 +/- 6.48 mL) and group 2 (13.54 +/- 3.12
      mL). The disappearance rate of varices was significantly greater in group 1
      (100%) than in group 2 (90.3%). Fever developed in 33.3% of patients in group 1
      and 87.1% of patients in group 2. The rates of recurrence of esophageal varices
      2, 4, and 9 years after the procedure were 34%, 48%, and 57%, respectively.
      CONCLUSION: These results show that catheter-retaining BRTO is a simple and
      highly effective procedure for difficult cases with minor complications.
      Furthermore, catheter-retaining BRTO does not require a large daily dose of EO
      and is, therefore, an effective treatment for solitary gastric varices.

PMID- 25391699
TI  - Association between serum lactate levels and early neurogenic pulmonary edema
      after nontraumatic subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Few studies have described the risk factors associated
      with the development of neurological pulmonary edema (NPE) after subarachnoid
      hemorrhage (SAH). We have hypothesized that acute-phase increases in serum
      lactate levels are associated with the early development of NPE following SAH.
      The aim of this study was to clarify the association between lactic acidosis and
      NPE in patients with nontraumatic SAH. METHODS: We retrospectively evaluated 140
      patients with nontraumatic SAH who were directly transported to the Nippon
      Medical School Hospital emergency room by the emergency medical services. We
      compared patients in whom NPE developed (NPE group) and those in whom it did not
      (non-NPE group). RESULTS: The median (quartiles 1-3) arrival time at the hospital
      was 32 minutes (28-38 minutes) after the emergency call was received. Although
      the characteristics of the NPE and non-NPE groups, including mean arterial
      pressure (121.3 [109.0-144.5] and 124.6 [108.7-142.6] mm Hg, respectively;
      P=0.96), were similar, the median pH and the bicarbonate ion (HCO3(-))
      concentrations were significantly lower in the NPE group than in the non-NPE
      group (pH, 7.33 [7.28-7.37] vs. 7.39 [7.35-7.43]); P=0.002; HCO3(-), 20.8 [18.6
      22.6] vs. 22.8 [20.9-24.7] mmol/L; P=0.01). The lactate concentration was
      significantly higher in the NPE group (54.0 [40.3-61.0] mg/dL) than in the non
      NPE group (28.0 [17.0-37.5] mg/dL; P<0.001). Multivariable regression analysis
      indicated that younger age and higher glucose and lactate levels were
      significantly associated with the early onset of NPE in patients with SAH.
      CONCLUSION: The present findings indicate that an increased serum lactate level,
      occurring within 1 hour of the ictus, is an independent factor associated with
      the early onset of NPE. Multicenter prospective studies are required to confirm
      our results.

PMID- 25391700
TI  - Subcutaneous angiolipoma: magnetic resonance imaging features with histological
      correlation.
AB  - PURPOSE: Despite producing pain, angiolipoma is sometimes misdiagnosed as an
      ordinary small lipoma, which is usually not associated with pain. Few reports
      have described magnetic resonance (MR) imaging findings of angiolipoma. The aim
      of the present study was to clarify the MR imaging features of angiolipoma.
      MATERIALS AND METHODS: The MR imaging findings of 11 lesions in 7 patients were
      reviewed and compared with histopathological findings. RESULTS: The MR imaging
      features of these lesions were the presence of fat nodules with or without areas
      of low signal intensity on T1- and T2-weighted images. The location of the low
      signal-intensity areas varied. The low-signal-intensity areas were mainly in the
      peripheral portion of 3 lesions and in the central portion of 5 lesions. No or
      few low-signal-intensity areas were observed in 3 lesions. In the lesions with
      peripheral low-signal-intensity areas, lesion marginations were well defined, and
      the lesions were easily recognized as mass lesions. In the lesions with only
      central low-signal-intensity areas, marginations were poorly defined, and the
      lesions were not easy to recognize as mass lesions. In the lesions with few or
      without low-signal-intensity areas, marginations were invisible.
      Histopathological studies indicated that the low-signal-intensity areas on T1-
      and T2-weighted images corresponded to areas of dense capillary proliferation. In
      lesions with few or without low-signal-intensity areas on MR images, capillaries
      were thinly spread over almost the entire lesion area. CONCLUSION: The MR imaging
      features of angiolipoma are fat nodules with or without low-signal-intensity
      areas of various size and location on T1- and T2-weighted images.

PMID- 25391701
TI  - Preventable trauma deaths after traffic accidents in Chiba Prefecture, Japan,
      2011: problems and solutions.
AB  - INTRODUCTION: The incidence of preventable trauma death in the current Japanese
      emergency medical system remains high. The present study aimed to determine rates
      of clearly preventable and possibly preventable trauma deaths due to traffic
      accidents in Chiba Prefecture, Japan, and to consider associated problems and
      solutions. MATERIALS AND METHODS: During 2011, 175 victims died after traffic
      accidents in Chiba Prefecture. Of these, the deaths of 69 persons who had vital
      signs at the time of emergency medical service contact were classified as clearly
      preventable, possibly preventable, or not preventable through the peer review
      discussion. We also examined problems associated with deaths that were clearly
      preventable or possibly preventable. RESULTS: Of the 69 deaths, 9 (13%) were
      classified as clearly preventable, 11 (16%) as possibly preventable, and 49 (71%)
      as not preventable. Of the 20 clearly or possibly preventable deaths (each death
      potentially comprising multiple problems), 5 were related to selection of the
      hospital before hospital arrival, 4 to problems with regional emergency medical
      systems, and 15 to inappropriate hemodynamic management, including transfusion
      and delayed (or not attempted) hemostasis in the hospital. DISCUSSION: Problems
      of these 20 deaths showed that appropriate triage at the scene, centralization of
      patients with severe trauma, and trauma centers are necessary in Japan. Under
      triage before arrival at the hospital was related to clearly and possibly
      preventable deaths. Upgrading the triage category for victims with torso injury
      must be considered. Not all emergency critical care centers in Japan are able to
      provide severe trauma care. Preventable trauma deaths occur even in some
      emergency critical care centers; therefore, we need centralization of severe
      trauma patients from wider area to reduce the incidence of preventable trauma
      death.

PMID- 25391702
TI  - Effect on clinical work practice of establishing a neonatal intensive care unit
      at a medical school-affiliated teaching hospital.
AB  - OBJECTIVE: The aim of this study was to examine the effects of a newly
      established neonatal intensive care unit (NICU) on clinical work practice and
      educational activity at Nippon Medical School Musashikosugi Hospital. METHODS:
      This retrospective study analyzed the clinical records of all neonates admitted
      to the NICU from December 2010 through November 2013. Anthropometric data,
      clinical status, problems, and outcomes of patients and the related obstetrical
      history were extracted and analyzed. RESULTS: Of the 568 neonatal admissions,
      about half were related to preterm birth (49%) and low birth weight (55%). Forty
      eight percent of patients were born via caesarean delivery. Maternal
      hypertension, diabetes, and thyroid disease were found in 8%, 5%, and 2% of
      cases, respectively. Mechanical ventilatory support was provided for 20% of
      patients. Neonates from multiple pregnancy and with significant congenital
      anomalies accounted for 17% and 10% of all patients, respectively. Five patients
      died during hospitalization. In addition training was provided in the NICU for an
      average of 10 residents and 20 medical students per year. CONCLUSION: Since the
      NICU was established, closer cooperation beyond the framework of a single
      department has come to be needed. In addition, NICUs in teaching hospitals are
      expected to provide opportunities for medical students and residents to observe
      and participate in multidisciplinary medical care.

PMID- 25391703
TI  - Grade 4 epistaxis in a woman with metastatic breast cancer treated with
      bevacizumab: a case report.
AB  - We describe a 39-year-old woman with metastatic breast cancer who had grade 4
      epistaxis induced by bevacizumab. The patient visited our outpatient clinic with
      complaints of a lump in her right breast, fatigue, dyspnea, abdominal distention,
      appetite loss, and weight loss of 10 kg over 1 year. Liver dysfunction was
      detected, with elevated levels of aspartate aminotransferase (271 IU/L), alanine
      aminotransferase (100 IU/L), alkaline phosphatase (4,205 IU/L), total bilirubin
      (2.7 mg/dL), and direct bilirubin (2.1 mg/dL). A secondary liver tumor that
      occupied most of the liver volume was found, and bone metastasis, ascites, and
      pleural effusion were also discovered. The Eastern Cooperative Oncology Group
      performance status was 2. A core needle biopsy of the right breast tumor revealed
      invasive ductal carcinoma of the breast (nuclear grade 1) that was positive for
      estrogen receptor and progesterone receptor and negative for human epidermal
      growth factor receptor 2 overexpression and had a high Ki-67 score. We chose
      combination chemotherapy with paclitaxel (80 mg/m(2) on days 1, 8, and 15) and
      bevacizumab (10 mg/kg on days 1 and 15) for 28 days (1 cycle). After completion
      of the first cycle of chemotherapy, the ascites and pleural effusion decreased,
      and the metastatic liver tumor shrank. The performance status improved from 2 to
      1. On day 3 of the third cycle of chemotherapy, however, she began having
      persistent epistaxis. On day 6, she lost consciousness and was transported to the
      emergency room of our hospital. The hemoglobin level was 5.6 g/dL. Blood
      transfusion and endoscopic hemostasis were immediately started. Bevacizumab was
      discontinued, and paclitaxel alone was continued; after this change, epistaxis
      did not recur. 

PMID- 25391704
TI  - Hydrocephalus with spontaneous regression in a 14-year-old girl.
AB  - We report on a 14-year-old girl with hydrocephalus that underwent spontaneous
      regression without any specific treatment, such as ventriculoperitoneal shunt
      surgery. A 14-year-old girl was referred to our hospital with severe headache,
      dizziness, nausea, and vomiting. Computed tomography and FLAIR-MRI findings on
      admission showed markedly dilated lateral, third and fourth ventricles with
      periventricular hyperintensity and downward displacement of the tonsils induced
      by dilatation of the fourth ventricle. We diagnosed hydrocephalus of unknown
      etiology. Although no specific treatment for hydrocephalus was performed, the
      symptoms gradually improved. One year after onset, the patient was completely
      free of neurological symptoms, and findings of physical examination and magnetic
      resonance imaging of the brain had returned to normal. The etiology of the
      spontaneous regression is unclear, but the following mechanisms are discussed: 1)
      rupture of ventricular diverticulum, 2) head injury causing skull-base fracture
      with leakage of cerebrospinal fluid, 3) extremely radiosensitive neoplasms
      diminished by X-p exploration, and 4) cerebrospinal fluid leakage due to lumbar
      puncture. 

PMID- 25391705
TI  - Treatment of visceral malperfusion in acute type B aortic dissection by
      percutaneous endovascular fenestration using a stent, with additional stenting of
      the true lumen.
AB  - Patients with acute type B aortic dissection (ABAD) are often treated medically.
      However, ABAD is a potentially serious emergency if complicated by acute organ
      ischemia. The therapeutic strategy for ABAD with visceral malperfusion remains
      controversial. Because emergent surgery has a high mortality rate, emergent
      endovascular treatment can be performed instead. We report a case of endovascular
      fenestration with stenting for visceral malperfusion in ABAD. One stent was
      inserted across the intimal flap to keep the fenestrated site open, and another
      stent was placed into the narrowed true lumen. This therapeutic strategy may be
      feasible for ABAD with acute malperfusion. 

PMID- 25391706
TI  - A case of nonfunctioning pancreatic endocrine tumor with atypical imaging
      findings due to prominent fibrosis of the tumor stroma.
AB  - The patient, a 56-year-old woman, was found during routine checkup to have a
      disorder of hepatic function. Abdominal ultrasonography showed an ill-defined
      hypoechoic mass in the head and body of the pancreas; however, no blood-flow
      signal was observed within the tumor on Doppler ultrasonography. Abdominal
      computed tomography showed a low-density area in the arterial and portal venous
      phases. The lesion was visualized as an area of low signal intensity on both T1-
      and T2-weighted magnetic resonance images, whereas fluorodeoxyglucose positron
      emission tomography showed fluorodeoxyglucose accumulation in the tumor. Although
      a preoperative diagnosis was difficult to make, a rapid cytologic examination
      revealed evidence of a pancreatic endocrine tumor, and subtotal stomach
      preserving pancreaticoduodenectomy with portal vein resection was performed.
      Histopathological examination showed tumor cell nests scattered in abundant
      fibrotic tissue; the tumor cells had proliferated in a cord-like fashion and
      showed immunostaining for chromogranin A. Staining for fibroblast activation
      protein alpha was seen in the fibroblastic cells contained within the fibrous
      stroma surrounding the tumor cell nests, whereas both the fibroblastic cells in
      the tumor and those in the stroma showed a high rate of staining for
      thrombospondin. We presume that tumor-associated fibroblasts were involved in the
      fibrosis of the tumor stroma. 

PMID- 25391709
TI  - Drug holiday utilisation in ADHD-diagnosed children and adolescents in South
      Africa.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a prevalent
      disorder affecting people in all age groups. Pharmacological treatment with
      psychostimulants, specifically methylphenidate, is first line management. The
      ideal dosing regimen of methylphenidate is debatable with daily use being
      considered harmful by many. However, it is unknown if sporadic drug withdrawal is
      beneficial to management. The primary aim was to investigate drug holiday
      utilisation incidence. METHOD: The study comprised a drug utilisation review
      (DUR) and questionnaire-based survey. The DUR was conducted using a corporate
      retail pharmacy group database. Methylphenidate prescriptions were evaluated to
      determine possible drug holiday use through different analyses of dispensing
      patterns. The survey included several questions relating to drug holiday use.
      RESULTS: Drug holiday use was identified in both study populations. Weekends and
      school holidays were identified as common periods for drug holiday observation.
      Of the participants that provided reasons for drug holiday utilisation, half
      indicated that methylphenidate was only necessary for school activities. DUR
      results indicated that drug holidays appeared to be more commonly observed during
      March and December. CONCLUSIONS: Reasons for drug holiday utilisation were
      variable. This study recommends that these drug free periods are only observed if
      shown to be beneficial to the patient.

PMID- 25391708
TI  - Emergency and critical care management of acute ischaemic stroke.
AB  - Ischaemic stroke is a devastating condition that is the leading cause of
      disability in the USA. Over the last 2 decades, the focus of management has
      shifted from secondary stroke prevention to acute treatment. Coordinated care
      starts in the field with the emergency medical service providers and continues in
      the ambulance and the emergency department through to the intensive care unit.
      After diagnosis and stabilization, a major goal is reperfusion therapy with
      intravenous fibrinolytics. Neuroimaging research is focused on improving patient
      selection, expanding treatment windows, and increasing the safety of therapeutic
      intervention. The role of adjunctive intra-arterial and mechanical thrombectomy
      remains undefined, and methods to improve reperfusion using sonolysis and new
      generation fibrinolytics are currently investigational. Treatment in the
      intensive care unit targets prevention of secondary brain injury through
      optimization of blood pressure, cerebral perfusion, glucose, and temperature
      management, ventilation, and oxygenation. The most feared complications include
      malignant cerebral edema and symptomatic hemorrhagic transformation.
      Decompressive craniectomy is life saving, but questions regarding patient
      selection and timing remain. Hyperosmolar agents are currently used to mitigate
      cerebral edema, but newer agents to prevent the formation of cerebral edema at
      the molecular level are being studied. We outline a practical approach to current
      emergency and intensive care management based on consensus guidelines and the
      best available evidence. 

PMID- 25391710
TI  - New developments in diagnosis and treatment update: Schizophrenia/first episode
      psychosis in children and adolescents.
AB  - Childhood onset schizophrenia (COS) is diagnosed before the age of 13 years, and
      early onset schizophrenia (EOS) is diagnosed before the age of 18 years. EOS is
      considered extremely rare and its prevalence in comparison to the worldwide
      prevalence of schizophrenia (1%) has not adequately been studied. Patients who
      experience the first episode of psychosis need to be treated early and optimally
      to lessen the morbidity and improve the outcome of the illness. Treatment needs
      to be a combination of both pharmacological and non-pharmacological modalities.
      Pharmacological intervention is necessary for remission, improvement of positive
      symptoms and to aid with the efficacy of psychosocial interventions. There is a
      lack of efficacy and safety data of the use of antipsychotic medication in
      children, with most of the information available being extrapolations of adult
      data. An increased use of atypical antipsychotic drugs in the treatment of EOS
      has been accompanied by growing concern about the appropriate use and associated
      side effects in children and adolescents. This update highlights new
      developments, concepts and treatment trends in EOS. 

PMID- 25391711
TI  - The psychopharmacological management of eating disorders in children and
      adolescents.
AB  - In this review we synthesised current literature on the psychopharmacological
      management of eating disorders (EDs) in children and adolescents (C&As). We focus
      specifically on anorexia nervosa (AN), bulimia nervosa (BN) and binge eating
      disorder (BED). The treatment of EDs is determined by physical and psycho-social
      factors and needs. Pharmacological management should therefore be viewed and
      incorporated as one component of a multi-disciplinary comprehensive treatment
      plan for specific requirements of a patient depending on the stage of the
      disorder. As there is a dearth of studies evaluating the use of
      psychopharmacology for EDs in C&As we first review the findings from studies
      performed in adults and then discuss specific studies performed in C&As. We
      include information from reviews and treatment guidelines to assist the clinician
      with an approach to the use of psychopharmacological agents in the treatment of
      EDs in C&As. 

PMID- 25391707
TI  - Drug-induced cerebellar ataxia: a systematic review.
AB  - BACKGROUND AND OBJECTIVES: Cerebellar ataxia can be induced by a large number of
      drugs. We here conducted a systemic review of the drugs that can lead to
      cerebellar ataxia as an adverse drug reaction (ADR). METHODS: We performed a
      systematic literature search in Pubmed (1966 to January 2014) and EMBASE (1988 to
      January 2014) to identify all of the drugs that can have ataxia as an ADR and to
      assess the frequency of drug-induced ataxia for individual drugs. Furthermore, we
      collected reports of drug-induced ataxia over the past 20 years in the
      Netherlands by querying a national register of ADRs. RESULTS: Drug-induced ataxia
      was reported in association with 93 individual drugs (57 from the literature, 36
      from the Dutch registry). The most common groups were antiepileptic drugs,
      benzodiazepines, and antineoplastics. For some, the number needed to harm was
      below 10. Ataxia was commonly reversible, but persistent symptoms were described
      with lithium and certain antineoplastics. CONCLUSIONS: It is important to be
      aware of the possibility that ataxia might be drug-induced, and for some drugs
      the relative frequency of this particular ADR is high. In most patients, symptoms
      occur within days or weeks after the introduction of a new drug or an increase in
      dose. In general, ataxia tends to disappear after discontinuation of the drug,
      but chronic ataxia has been described for some drugs.

PMID- 25391716
TI  - Controversies in the use of antidepressants in children and adolescents: A decade
      since the storm and where do we stand now?

PMID- 25391712
TI  - Psychometric properties of instruments for assessing depression among African
      youth: A systematic review.
AB  - OBJECTIVE: This study aimed to systematically review the psychometric properties
      of instruments used to screen for major depressive disorder or assess depression
      symptom severity among African youth. METHODS: Systematic search terms were
      applied to seven bibliographic databases: African Journals Online, the African
      Journal Archive, the Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), Embase, the Medical Literature Analysis and Retrieval System Online
      (MEDLINE), PsycINFO, and the World Health Organization (WHO) African Index
      Medicus. Studies examining the reliability and/or validity of depression
      assessment tools were selected for inclusion if they were based on data collected
      from youth (any author definition) in an African member state of the United
      Nations. We extracted data on study population characteristics, sampling
      strategy, sample size, the instrument assessed, and the type of reliability
      and/or validity evidence provided. RESULTS: Of 1 027 records, we included 23
      studies of 10 499 youth in 10 African countries. Most studies reported excellent
      scale reliability, but there was much less evidence of equivalence or criterion
      related validity. No measures were validated in more than two countries.
      CONCLUSIONS: There is a paucity of evidence on the reliability or validity of
      depression assessment among African youth. The field is constrained by a lack of
      established criterion standards, but studies incorporating mixed methods offer
      promising strategies for guiding the process of cross-cultural development and
      validation.

PMID- 25391717
TI  - Cognitive effects of acute restraint stress in male albino rats and the impact of
      pretreatment with quetiapine versus ghrelin.
AB  - Stress is any condition that seriously affects the balance of the organism
      physiologically and psychologically. Stress activates the hypothalamic-pituitary
      adrenal (HPA) releasing glucocorticoid hormones that produce generalized effects
      on different body systems including the nervous system. This study aimed to
      investigate the effect of acute restraint stress (ARS) on cognitive performance
      by measuring spatial working memory in Y-maze, behavior (anxiety and exploratory
      behavior) in open field test, expression of synaptophysin and glial fibrillary
      acidic protein (GFAP) in the hippocampus by immunohistochemistry, dopaminergic
      receptors (D2) in the basal ganglia by gene expression and comparing the effect
      of ghrelin and quetiapine on the previous parameters. 36 adult male albino rats
      constituted the animal model of this work and have been divided into six groups:
      control group, control group exposed to ARS, quetiapine group, quetiapine group
      exposed to ARS, ghrelin group and ghrelin group exposed to ARS. We demonstrated
      more neuroprotective effect for quetiapine compared to ghrelin on stress
      response, anxiety behavior and working spatial memory impairment due to ARS. 

PMID- 25391718
TI  - Newly introduced sample preparation techniques: towards miniaturization.
AB  - Sampling and sample preparation are of crucial importance in an analytical
      procedure, representing quite often a source of errors. The technique chosen for
      the isolation of analytes greatly affects the success of a chemical
      determination. On the other hand, growing concerns about environmental and human
      safety, along with the introduction of international regulations for quality
      control, have moved the interest of scientists towards specific needs. Newly
      introduced sample preparation techniques are challenged to meet new criteria: (i)
      miniaturization, (ii) higher sensitivity and selectivity, and (iii) automation.
      In this survey, the most recent techniques introduced in the field of sample
      preparation will be described and discussed, along with many examples of
      applications. 

PMID- 25391719
TI  - Validation and quality control of an ICP-MS method for the quantification and
      discrimination of trace metals and application in paper analysis: an overview.
AB  - Questioned documents analysis includes: handwriting comparison, analysis of the
      ink and the printer used in the production of the documents, and the physical and
      chemical characterization of the cellulosic substrate (paper) of the documents.
      In many situations in life, for financial, social, and personal concerns, we
      depend on different documents. Therefore, over time, various analytical methods
      have been developed in order to determine their authenticity, source, and age or
      to differentiate various papers. In this study a quantitative analytical method
      for the determination of eight trace level chemical elements (Al, Ba, Fe, Mg, Mn,
      Pb, Sr, Zn) from document paper samples using inductively coupled plasma-mass
      spectrometry (ICP-MS) was validated and applied. The evaluation of the
      performance parameters of the method (applicability, fitness for purpose,
      linearity, working range, limit of detection and limit of quantification,
      sensitivity, accuracy, and precision) was accomplished. An overview of the
      validation parameters are presented and discussed in detail. 

PMID- 25391720
TI  - Progress in thermal lens spectrometry and its applications in microscale
      analytical devices.
AB  - Development of thermal lens spectrometry (TLS) as a micro space-compatible
      photothermal technique and its applications for analysis of different chemical
      compounds in micro space and particularly in microfluidic systems are reviewed.
      Theoretical treatment of TLS in micro space has evolved from simply following
      conventional theory and predictions in macro space to employing a more accurate
      theory where impacts of the excitation source (Gaussian laser, top-hat incoherent
      light source, beam divergence, power density), detection scheme (probe beam
      waist, mode-mismatching degree), sample flow, and sample cell (top/bottom layers,
      side wall) on the TL signal are included. Noise sources (light sources, sample
      status, detector) in TLS systems have been analyzed, and optimum pinhole-to-beam
      radius ratio is suggested for the maximum signal-to-noise ratio. With different
      excitation light sources from ultraviolet, to visible, to near-infrared regions
      and coupled with microfluidic devices, these TLS instruments with good temporal
      and spatial resolution have found many applications for highly sensitive and/or
      high-throughput detection of chemical or biochemical analytes, for cell imaging
      or single particle/molecule detection, and for characterization of molecular
      diffusion in single- or two-phase systems. Prospects and challenges of TLS for
      future applications in microchemical analysis are discussed. 

PMID- 25391721
TI  - DNA-templated lithography and nanofabrication for the fabrication of nanoscale
      electronic circuitry.
AB  - The field of structural DNA nanotechnology has undergone significant expansion in
      recent years as exciting new techniques and understanding have been developed,
      allowing for the design and assembly of complex and intricate two- and three
      dimensional nanostructures. Many of these designed DNA motifs have found use in
      precise positioning of nanomaterials and thereby can aid in studies, reactions,
      and assembly of other nanostructures. This review discusses the history and
      progression of DNA-based nanofabrication with an emphasis on the use of DNA
      nanostructures for electronics applications. 

PMID- 25391724
TI  - Vitellogenin in the male Lake Van fish (Chalcalburnus tarichi Pallas, 1811).
AB  - Chalcalburnus tarichi is an endemic cyprinid species living in Lake Van, Turkey.
      In the present study, we investigated vitellogenin (Vtg) in the plasma of adult
      male C. tarichi, sampled monthly from Edremit, Campus and Carpanak sites of Van
      Edremit Gulf (VEG) of lake, between October 2004 and May 2005. The fish living
      around VEG winters in deep water around Edremit site. University and Carpanak
      sites are also on fish migration way from VEG to fresh water (Karasu River). The
      levels of measured plasma Vtg changed from trace levels to 26.35 ug/mL. The
      highest level of plasma Vtg was detected in April, with a concentration of 21.60
      +/- 1.29 ug/mL. We also performed immunohistochemical Vtg staining in the liver
      sections of male fish and determined Vtg positive hepatocytes in the liver of
      1/10 sampled fish. Our results indicated that C. tarichi living in Lake Van might
      be exposed to endocrine-disrupting chemicals. 

PMID- 25391723
TI  - HCN2 channels: a permanent open state and conductance changes.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the
      membranes of heart and brain cells can conduct Na(+) and K(+) ions and activate
      between -30 and -120 mV. We express the alpha subunit of HCN2 channels in Xenopus
      laevis oocytes and are confronted with two unexpected problems. First, we observe
      a rise in membrane conductance at resting potential proportional to the amount of
      expression. On activation to hyperpolarizing potentials, the instantaneous
      conductance rises in proportion to the amount of activated current. CsCl reduces
      the observed effects. This can be explained by the expression in oocytes
      membranes of a fraction of permanently open HCN2 channels. Second, using TEVC
      technique, our data show a completely different behaviour in physiological
      solutions of heterogeneously expressed HCN2 currents from what is observed in
      wild-type currents in the absence of drugs. During pulse trains, we frequently
      observe (1) a fast and significant decline of the amplitude of HCN2 current
      during hyperpolarizing steps, (2) no recovery of this decline after a long period
      at resting membrane potential, (3) a different behaviour of the tail currents at
      depolarization with other and slower changes than during activation, (4) recovery
      of this decline in high K(+)/low Na(+) bath solution. The decline of the HCN2
      current in physiological conditions is caused by a reduction of the conductance
      of the HCN2 channel presumably caused by the mere presence of sodium in the
      channel, in competition with potassium ions and with a limitative effect on the
      channel conductance.

PMID- 25391725
TI  - Comprehensive lipidome analysis by shotgun lipidomics on a hybrid quadrupole
      orbitrap-linear ion trap mass spectrometer.
AB  - Here we report on the application of a novel shotgun lipidomics platform
      featuring an Orbitrap Fusion mass spectrometer equipped with an automated
      nanoelectrospray ion source. To assess the performance of the platform for in
      depth lipidome analysis, we evaluated various instrument parameters, including
      its high resolution power unsurpassed by any other contemporary Orbitrap
      instrumentation, its dynamic quantification range and its efficacy for in-depth
      structural characterization of molecular lipid species by quadrupole-based higher
      energy collisional dissociation (HCD), and ion trap-based resonant-excitation
      collision-induced dissociation (CID). This evaluation demonstrated that FTMS
      analysis with a resolution setting of 450,000 allows distinguishing isotopes from
      different lipid species and features a linear dynamic quantification range of at
      least four orders of magnitude. Evaluation of fragmentation analysis demonstrated
      that combined use of HCD and CID yields complementary fragment ions of molecular
      lipid species. To support global lipidome analysis, we designed a method, termed
      MS(ALL), featuring high resolution FTMS analysis for lipid quantification, and
      FTMS(2) analysis using both HCD and CID and ITMS(3) analysis utilizing dual CID
      for in-depth structural characterization of molecular glycerophospholipid
      species. The performance of the MS(ALL) method was benchmarked in a comparative
      analysis of mouse cerebellum and hippocampus. This analysis demonstrated
      extensive lipidome quantification covering 311 lipid species encompassing 20
      lipid classes, and identification of 202 distinct molecular glycerophospholipid
      species when applying a novel high confidence filtering strategy. The work
      presented here validates the performance of the Orbitrap Fusion mass spectrometer
      for in-depth lipidome analysis. 

PMID- 25391726
TI  - A novel route to recognizing quaternary ammonium cations using electrospray mass
      spectrometry.
AB  - Characterizing and elucidating structures is a commonplace and necessary activity
      in the pharmaceutical industry with mass spectrometry and NMR being the primary
      tools for analysis. Although many functional groups are readily identifiable,
      quaternary ammonium cations have proven to be difficult to unequivocally identify
      using these techniques. Due to the lack of an N-H bond, quaternary ammonium
      groups can only be detected in the (1)H NMR spectra by weak signals generated
      from long-range (14)N-H coupling, which by themselves are inconclusive evidence
      of a quaternary ammonium functional group. Due to their low intensity, these
      signals are frequently not detected. Additionally, ions cannot be differentiated
      in a mass spectrum as an M(+) or [M + H](+) ion without prior knowledge of the
      compound's structure. In order to utilize mass spectrometry as a tool for
      determining this functionality, ion cluster formation of quaternary ammonium
      cations and non-quaternary amines was studied using electrospray ionization.
      Several mobile phase modifiers were compared; however, the addition of small
      amounts of trifluoroacetic acid proved superior in producing characteristic and
      intense [M +2TFA](-) clusters for compounds containing quaternary ammonium
      cations when using negative electrospray. By fragmenting this characteristic ion
      using CID, nearly all compounds studied could be unambiguously identified as
      containing a quaternary ammonium cation or a non-quaternary amine attributable to
      the presence (non-quaternary amine) or absence (quaternary ammonium cation) of
      the resulting [2TFA + H](-) ion in the product spectra. This method of analysis
      provides a rapid, novel, and reliable technique for indicating the presence of
      quaternary ammonium cations in order to aid in structural elucidation. 

PMID- 25391727
TI  - The assessment of selectivity in different Quadrupole-Orbitrap mass spectrometry
      acquisition modes.
AB  - Selectivity of the confirmation of identity in liquid chromatography (tandem)
      mass spectrometry using Q-Orbitrap instrumentation was assessed using different
      acquisition modes based on a representative experimental data set constructed
      from 108 samples, including six different matrix extracts and containing over 100
      analytes each. Single stage full scan, all ion fragmentation, and product ion
      scanning were applied. By generating reconstructed ion chromatograms using unit
      mass window in targeted MS(2), selected reaction monitoring (SRM), regularly
      applied using triple-quadrupole instruments, was mimicked. This facilitated the
      comparison of single stage full scan, all ion fragmentation, (mimicked) SRM, and
      product ion scanning applying a mass window down to 1 ppm. Single factor Analysis
      of Variance was carried out on the variance (s(2)) of the mass error to determine
      which factors and interactions are significant parameters with respect to
      selectivity. We conclude that selectivity is related to the target compound
      (mainly the mass defect), the matrix, sample clean-up, concentration, and mass
      resolution. Selectivity of the different instrumental configurations was
      quantified by counting the number of interfering peaks observed in the
      chromatograms. We conclude that precursor ion selection significantly contributes
      to selectivity: monitoring of a single product ion at high mass accuracy with a 1
      Da precursor ion window proved to be equally selective or better to monitoring
      two transition products in mimicked SRM. In contrast, monitoring a single
      fragment in all ion fragmentation mode results in significantly lower selectivity
      versus mimicked SRM. After a thorough inter-laboratory evaluation study, the
      results of this study can be used for a critical reassessment of the current
      identification points system and contribute to the next generation of evidence
      based and robust performance criteria in residue analysis and sports doping. 

PMID- 25391728
TI  - A method to label biological molecules with dsDNA coated gold nanoparticles.
AB  - We described a new method to label biological molecules using gold nanoparticles
      (GNPs) and double stranded DNA. Researchers can conveniently label their own
      samples with GNPs using this method. The label is based on dsDNA with a 93.5%
      coverage of GNPs (dsDNA:GNP = 303:1). Antigens, streptavidin and biotin were
      labeled on GNPs and the success of the method was investigated with agarose gel
      electrophoresis, laser particle size analysis and ultraviolet spectrophotometry.
      These analyses confirmed that biological molecules were successfully bound to the
      GNPs. These molecules retained their biological activity and were able to detect
      targets on PVDF and NC membranes with excellent selectivity and low levels of
      background. Modified GNPs were also able to detect targets on nylon membranes,
      but with some degree of false positives. The maximum limit of detection was 25 ng
      proteins.

PMID- 25391729
TI  - Characterization of a GH family 8 beta-1,3-1,4-glucanase with distinctive broad
      substrate specificity from Paenibacillus sp. X4.
AB  - A beta-1,3-1,4 glucanase gene of Paenibacillus sp. X4, bglc8H, was cloned and
      characterized. BGlc8H was predicted to be a protein of 409 amino acid residues,
      including a signal peptide of 31 amino acids. The mature enzyme was predicted to
      have 378 amino acid residues; its [corrected] molecular mass and pI were
      estimated as 41,561 Da and 7.61, respectively. BGlc8H belongs to glycoside
      hydrolase family 8 (GH8). Site-directed mutants of Glu95 and Asp156 of BGlc8H
      showed a near-complete loss of activity, indicating that they are catalytically
      active residues. Unlike other GH8 members, BGlc8H had broad substrate specificity
      and hydrolyzed barley-beta-D-glucan > chitosan > carboxymethyl-cellulose > and
      lichenan. BGlc8H had a lower ratio of lichenase/barley-beta-D-glucanase
      activities compared to GH16 enzymes. BGlc8H was optimally active at pH 5 and 50 
      degrees C, except for barley-beta-D-glucanase (40  degrees C) and chitosanase (pH
      7) activities. BGlc8H hydrolyzed cello-oligosaccharides (G3-G6) to G3 and G2 but
      not to G1. Ca(2+) increased the activity and thermostability of BGlc8H for
      lichenan suggesting its use for the saccharification of cellulosic biomass.

PMID- 25391730
TI  - Spread and adoption of enhanced recovery from elective surgery in the English
      National Health Service.

PMID- 25391731
TI  - Enhanced Recovery After Surgery (ERAS): good for now, but what about the future?

PMID- 25391732
TI  - Prevention of venous thromboembolism in the Enhanced Recovery After Surgery
      (ERAS) setting: an evidence-based review.
AB  - PURPOSE: To review the evidence surrounding appropriate prophylaxis for venous
      thromboembolism (VTE) in patients undergoing surgery. PRINCIPAL FINDINGS:
      Appropriate prophylactic strategies for surgical patients have been defined in
      major society guidelines. We review the evidence behind these guidelines in a
      case-based format, including patients with a high risk of bleeding, history of
      heparin-induced thrombocytopenia, obesity, and cancer. Selecting the most
      suitable means for VTE prophylaxis includes evaluating patient, anesthetic, and
      surgical factors. Nevertheless, pharmacologic VTE prophylaxis will be appropriate
      for the vast majority of inpatients undergoing surgery. CONCLUSIONS: Venous
      thromboembolism is a serious but preventable complication of hospitalization,
      especially among surgical patients. Historically, it has accounted for a high
      burden of postoperative morbidity and mortality. In the Enhanced Recovery After
      Surgery era, our aim should be no less ambitious than the eradication of
      postoperative VTE.

PMID- 25391733
TI  - What outcomes are important in the assessment of Enhanced Recovery After Surgery
      (ERAS) pathways?
AB  - PURPOSE: The purpose of this narrative review is to provide a framework from
      which to measure the outcomes of Enhanced Recovery After Surgery (ERAS) programs.
      PRINCIPLE FINDINGS: We define the outcomes of recovery from the perspective of
      different stakeholders and time frames. There is no single definition of
      recovery. There are overlapping phases of recovery which are of particular
      interest to different stakeholders (surgeons, anesthesiologists, nurses, patients
      and their caregivers), and the primary outcome of interest may vary depending on
      the phase and the perspective. In the earliest phase (from the end of the surgery
      to discharge from the postanesthesia care unit [PACU]), biologic and physiologic
      outcomes are emphasized. In the intermediate phase (from PACU to discharge from
      the hospital), symptoms related to pain and gastrointestinal function as well as
      basic activities are important. Studies of ERAS pathways have reported clinical
      outcomes and symptoms, including complications, hospital stay, mobilization, and
      gastrointestinal function, largely during hospitalization. Nevertheless, patients
      define recovery as return to normal functioning, a process that occurs over weeks
      to months (late phase). Outcomes reflecting functional status (e.g., physical
      activity, activities of daily living) and overall health (e.g., quality of life)
      are important in this phase. To date, few studies reporting the effectiveness of
      ERAS pathways compared with conventional care have included functional status or
      quality-of-life outcomes, and there is little information about recovery after
      discharge from hospital. CONCLUSION: Recovery after surgery is a complex
      construct. Different outcomes are important at different phases along the
      recovery trajectory. Measures for quantifying recovery in hospital and after
      discharge are available. A consensus-based core set of outcomes with input from
      multiple stakeholders would facilitate research reporting.

PMID- 25391734
TI  - Inter-device differences in monitoring for goal-directed fluid therapy.
AB  - PURPOSE: Goal-directed fluid therapy is an integral component of many Enhanced
      Recovery After Surgery (ERAS) protocols currently in use. The perioperative
      clinician is faced with a myriad of devices promising to deliver relevant
      physiologic data to better guide fluid therapy. The goal of this review is to
      provide concise information to enable the clinician to make an informed decision
      when choosing a device to guide goal-directed fluid therapy. PRINCIPAL FINDINGS:
      The focus of many devices used for advanced hemodynamic monitoring is on
      providing measurements of cardiac output, while other, more recent, devices
      include estimates of fluid responsiveness based on dynamic indices that better
      predict an individual's response to a fluid bolus. Currently available
      technologies include the pulmonary artery catheter, esophageal Doppler, arterial
      waveform analysis, photoplethysmography, venous oxygen saturation, as well as
      bioimpedance and bioreactance. The underlying mechanistic principles for each
      device are presented as well as their performance in clinical trials relevant for
      goal-directed therapy in ERAS. CONCLUSIONS: The ERAS protocols typically involve
      a multipronged regimen to facilitate early recovery after surgery. Optimizing
      perioperative fluid therapy is a key component of these efforts. While no
      technology is without limitations, the majority of the currently available
      literature suggests esophageal Doppler and arterial waveform analysis to be the
      most desirable choices to guide fluid administration. Their performance is
      dependent, in part, on the interpretation of dynamic changes resulting from
      intrathoracic pressure fluctuations encountered during mechanical ventilation.
      Evolving practice patterns, such as low tidal volume ventilation as well as the
      necessity to guide fluid therapy in spontaneously breathing patients, will
      require further investigation.

PMID- 25391735
TI  - Fluid management and goal-directed therapy as an adjunct to Enhanced Recovery
      After Surgery (ERAS).
AB  - Optimal perioperative fluid management is an important component of Enhanced
      Recovery After Surgery (ERAS) pathways. Fluid management within ERAS should be
      viewed as a continuum through the preoperative, intraoperative, and postoperative
      phases. Each phase is important for improving patient outcomes, and suboptimal
      care in one phase can undermine best practice within the rest of the ERAS
      pathway. The goal of preoperative fluid management is for the patient to arrive
      in the operating room in a hydrated and euvolemic state. To achieve this,
      prolonged fasting is not recommended, and routine mechanical bowel preparation
      should be avoided. Patients should be encouraged to ingest a clear carbohydrate
      drink two to three hours before surgery. The goals of intraoperative fluid
      management are to maintain central euvolemia and to avoid excess salt and water.
      To achieve this, patients undergoing surgery within an enhanced recovery protocol
      should have an individualized fluid management plan. As part of this plan, excess
      crystalloid should be avoided in all patients. For low-risk patients undergoing
      low-risk surgery, a "zero-balance" approach might be sufficient. In addition, for
      most patients undergoing major surgery, individualized goal-directed fluid
      therapy (GDFT) is recommended. Ultimately, however, the additional benefit of
      GDFT should be determined based on surgical and patient risk factors.
      Postoperatively, once fluid intake is established, intravenous fluid
      administration can be discontinued and restarted only if clinically indicated. In
      the absence of other concerns, detrimental postoperative fluid overload is not
      justified and "permissive oliguria" could be tolerated.

PMID- 25391736
TI  - Cinching the loop on the Arndt endobronchial blocker during placement for
      descending aortic aneurysm surgery.

PMID- 25391737
TI  - An improvised pressurization system for arterial lines.

PMID- 25391738
TI  - A prospective observational study comparing the ease of use and safety of two
      neuraxial anesthesia kits on an epidural-spinal training model.

PMID- 25391739
TI  - Health economics in Enhanced Recovery After Surgery programs.
AB  - PURPOSE: The Enhanced Recovery After Surgery (ERAS) program aims to combine and
      coordinate evidence-based perioperative care interventions that support
      standardizing and optimizing surgical care. In conjunction with its clinical
      benefits, it has been suggested that ERAS reduces costs through shorter
      convalescence and reduced morbidity. Nevertheless, few studies have evaluated the
      cost-effectiveness of ERAS programs. The aim of this systematic review,
      therefore, is to evaluate the claims that ERAS is cost-effective and to
      characterize how these costs were reported and evaluated. SOURCE: The electronic
      databases, MEDLINE((r)) and EMBASETM, were searched from inception to April 2014.
      PRINCIPAL FINDINGS: Seventeen studies met the inclusion criteria and were
      included for review. Enhanced Recovery After Surgery protocols in various
      abdominal surgeries have been investigated, including colorectal, bariatric,
      gynecological, gastric, pancreatic, esophageal, and vascular surgery. All studies
      reported cost savings associated with hastening recovery and reducing morbidity
      and complications. All studies included in this review focused primarily on in
      hospital costs, with some attempting to account for readmission costs and follow
      up services. In all but two studies, the breakdown of cost data for the
      individual studies was poorly detailed. CONCLUSIONS: In conclusion, ERAS
      protocols appear to be both clinically efficacious and cost effective across a
      variety of surgical specialties in the short term. Nevertheless, studies
      reporting out-of-hospital cost data are lacking. Further research is required to
      determine how best to evaluate both medium- and long-term costs relating to ERAS
      pathways while taking quality of life data into account.

PMID- 25391740
TI  - [Skin manifestations are among the first and most frequent symptoms of Lyme
      borreliosis].

PMID- 25391741
TI  - [The Birt-Hogg-Dube Syndrome].

PMID- 25391743
TI  - [How does chocolate impact vascular function?].
AB  - For thousands of years, cocoa have been a very popular food and has been linked
      to various beneficial health effects. Observational and epidemiological studies
      point towards a beneficial effect of dark chocolate on cardiovascular morbidity.
      Several small, albeit controlled studies indeed demonstrate an amelioration of
      endothelial dysfunction - the dysfunction of the inner layer of the vessels -
      after intake of dark, flavanol-rich chocolate. This is important, as endothelial
      dysfunction is an important marker of the development of atherosclerosis and an
      important prognosticator of future cardiovascular events. This article summarizes
      the actual literature in this respect. 

PMID- 25391744
TI  - [Pre-anesthetic fluid and food intake- current recommendations].
AB  - Preoperative fasting is essential to reduce the risk of a perioperative pulmonary
      aspiration in patients undergoing anaesthesia for elective surgery. Evidence and
      expert opinion-based guidelines suggest two, four and six hours of fasting for
      clear fluids, breast milk and light meals/non-clear fluids respectively to
      improve anaesthesia safety, patient's comfort and homeostasis. Prolonged fasting
      is observed in daily clinical routine but should be prevented since there are no
      benefits. Abnormal gastric emptying has an impact on preoperative fasting times
      and the choice of the anaesthesia technique. A safe anaesthesia technique is most
      important since gastric emptying differs in patients and there is no guarantee
      that the stomach is empty after fasting according to guidelines. 

PMID- 25391745
TI  - [Low-grade gliomas in adults].
AB  - Low-grade gliomas (LGG) are brain tumors with a low or intermediate biological
      aggressiveness. According to histopathological features, they are further
      specified as grade I or II by WHO criteria. Diffuse astrocytomas,
      oligodendrogliomas, and mixed gliomas are the most common LGG. They mainly affect
      young patients in their 3rd to 5th decade and often manifest with epileptic
      seizures. A macroscopically complete or near-complete tumor resection that does
      not induce additional neurological deficits, is recommended as first line therapy
      in surgically accessible tumors, as a significant benefit for overall survival
      has been demonstrated. The indication for adjuvant chemo- or radiotherapy must be
      discussed interdisciplinary in each case. MGMT promotor methylation, LOH 1p/19q,
      as well as the status of somatic mutations within IDH1/2 gene constitute
      biomarkers that may predict response to adjuvant therapy and may correlate to
      overall survival. These and other biomarkers could be of benefit in future
      managing plans to offer patients with LGG an individually tailored, optimal
      treatment. 

PMID- 25391746
TI  - [Why is my foot swollen and red?].
AB  - We present the case of a 26 year old man reporting to the family doctor due to
      swelling and redness of the foot. After thrombosis and a tumorous mass could be
      excluded, the suspicion fell on an acrodermatitis chronica atrophican which could
      be confirmed by laboratory tests. During therapy there was a significant
      regression of the cutaneous lesion. The treatment of the Lyme disease was taken
      over by the casualty insurer. 

PMID- 25391748
TI  - [Shoulder impingement syndrome: steroid injections are not superior to manual
      physical therapy].

PMID- 25391749
TI  - [Physical activity after gestational diabetes is essential].

PMID- 25391751
TI  - [CME dermatology 6. Light spots on the trunk. Progressive macular hypomelanosis].

PMID- 25391753
TI  - [Personalities in the history of medicine].

PMID- 25391754
TI  - Attachment site selection of life stages of Ixodes ricinus ticks on a main large
      host in Europe, the red deer (Cervus elaphus).
AB  - BACKGROUND: Ticks and tick-borne diseases are increasing in many areas of Europe
      and North America due to climate change, while land use and the increased
      abundances of large hosts play a more controversial role. The pattern of host
      selection involves a crucial component for tick abundance. While the larvae and
      nymphs feed on a wide range of different sized hosts, the adult female ticks
      require blood meal from a large host (>1 kg), typically a deer, to fulfil the
      life cycle. Understanding the role of different hosts for abundances of ticks is
      therefore important, and also the extent to which different life stages attach to
      large hosts. FINDINGS: We studied attachment site selection of life stages of I.
      ricinus ticks on a main large host in Europe, the red deer (Cervus elaphus). We
      collected from 33 felled red deer pieces of skin from five body parts: leg,
      groin, neck, back and ear. We counted the number of larval, nymphal, adult male
      and adult female ticks. Nymphs (42.2%) and adult (48.7%) ticks dominated over
      larvae (9.1%). There were more larvae on the legs (40.9%), more nymphs on the
      ears (83.7%), while adults dominated in the groins (89.2%) and neck (94.9%).
      CONCLUSIONS: Large mammalian hosts are thus a diverse habitat suitable for
      different life stages of ticks. The attachment site selection reflected the life
      stages differing ability to move. The spatial separation of life stages may
      partly limit the role of deer in co-feeding transmission cycles.

PMID- 25391755
TI  - Bone fractures and feeling at risk for osteoporosis among women in Japan: patient
      characteristics and outcomes in the National Health and Wellness Survey.
AB  - Women aged 50 and older in Japan were compared according to perceived risk for
      osteoporosis and fracture history. Perceived risk was associated with family
      history of osteoporosis but few other risk factors. Few felt at risk, and
      perception was only loosely related to epidemiological risks, indicating a need
      for patient education. PURPOSE: Osteoporosis is prevalent but underdiagnosed and
      undertreated. This study was conducted to explore characteristics associated with
      history of fractures and feeling at risk for osteoporosis in women aged 50 and
      older in Japan. METHODS: Data were provided by a large annual survey
      representative of Japanese aged 18 and older. Women 50 and older without
      diagnosed osteoporosis were categorized into four mutually exclusive groups based
      on fracture history since age 50 and feeling at risk for developing osteoporosis.
      Sociodemographic and health characteristics were compared across groups using
      bivariate statistics, and health outcomes were compared using generalized linear
      models. RESULTS: A total of 16,801 women aged 50 and older were included in the
      analyses. Most (n = 12,798; 76.2 %) had no fracture since age 50 and did not feel
      at risk for osteoporosis, 12.9 % (n = 2170) felt at risk but had no fracture, 8.7
      % (n = 1455) did not feel at risk despite having a fracture, and 2.2 % (n = 378)
      had a fracture and felt at risk for osteoporosis. Feeling at risk was slightly
      more common among those with than without a fracture since age 50 (20.6 vs. 14.5
      %, p < 0.001). Feeling at risk was most associated with family history of
      osteoporosis, though known risk factors for fracture did not significantly differ
      across the fracture/perceived-risk group. CONCLUSIONS: Approximately 15 % of
      women in Japan aged 50 and older felt at risk for developing osteoporosis in the
      future, far fewer than expected by epidemiologists. Risk perception was only
      loosely related to epidemiological risks for fracture, indicating a need for
      patient education.

PMID- 25391756
TI  - Theoretical design of multi-colored semi-transparent organic solar cells with
      both efficient color filtering and light harvesting.
AB  - Solar cells incorporated with multi-coloring capability not only offer an
      aesthetic solution to bridge the gap between solar modules and building
      decorations but also open up the possibility for self-powered colorful display.
      In this paper, we proposed a multi-colored semi-transparent organic solar cells
      (TOSCs) design containing metallic nanostructures with the both high color purity
      and efficiency based on theoretical considerations. By employing guided mode
      resonance effect, the multi-colored TOSC behave like an efficient color filter
      that selectively transmits light with the desired wavelengths and generates
      electricity with light of other wavelengths. Broad range of coloring and
      luminosity adjusting for the transmission light can be achieved by simply tuning
      the period and the duty cycle of the metallic nanostructures. Furthermore,
      accompanying with the efficient color filtering characteristics, the optical
      absorption of TOSCs was improved due to the marked suppression of transmission
      loss at the off-resonance wavelengths and the increased light trapping in TOSCs.
      The mechanisms of the light guiding in photoactive layer and broadband backward
      scattering from the metallic nanostructures were identified to make an essential
      contribution to the improved light-harvesting. By enabling efficient color
      control and high efficiency simultaneously, this approach holds great promise for
      future versatile photovoltaic energy utilization. 

PMID- 25391757
TI  - Light-to-moderate alcohol intake reduces lipid accumulation product and
      attenuates its relation to hypertension.
AB  - Lipid accumulation product (LAP), an index calculated by using triglyceride level
      and waist circumference, has been shown to predict hypertension, diabetes and
      cardiovascular disease. Alcohol is known to influence blood pressure and blood
      lipids. The aim of this study was to clarify the relationships among alcohol
      intake, LAP and hypertension. The subjects, middle-aged Japanese men (n=21,572),
      were divided into non-, light (<22 g ethanol per day), moderate (? 22 and<44 g
      ethanol per day) and heavy (? 44 g ethanol per day) drinkers. The relationships
      between alcohol intake and LAP and between LAP and hypertension were
      investigated. There were U- and J-shaped relationships between alcohol intake and
      LAP in subjects with and without hypertension, respectively. The adjusted odds
      ratios with their 95% confidence intervals for hypertension in subjects with vs
      subjects without high LAP were 3.04 (2.69-3.43, P<0.01), 2.32 (1.92-2.81,
      P<0.01), 2.10 (1.89-2.33, P<0.01) and 2.11 (1.87-2.38, P<0.01) in non-, light,
      moderate and heavy drinkers, respectively. Thus, the positive association between
      LAP and hypertension is weaker in drinkers than in nondrinkers. The results
      suggest that light-to-moderate alcohol drinking reduces LAP level in patients
      with hypertension and attenuates the relation of LAP to hypertension.

PMID- 25391758
TI  - Association of left ventricular diastolic dysfunction with 24-h aortic ambulatory
      blood pressure: the SAFAR study.
AB  - Aortic blood pressure (BP) and 24-h ambulatory BP are both better associated with
      target organ damage than office brachial BP. However, it remains unclear whether
      a combination of these two techniques would be the optimal methodology to
      evaluate patients' BP in terms of left ventricular diastolic dysfunction (LVDD)
      prevention. In 230 participants, office brachial and aortic BPs were measured by
      a validated BP monitor and a tonometry-based device, respectively. 24-h
      ambulatory brachial and aortic BPs were measured by a validated ambulatory BP
      monitor (Mobil-O-Graph, Germany). Systematic assessment of patients' LVDD was
      performed. After adjustment for age, gender, hypertension and antihypertensive
      treatment, septum and lateral E/Ea were significantly associated with office
      aortic systolic BP (SBP) and pulse pressure (PP) and 24-h brachial and aortic SBP
      and PP (P ? 0.04), but not with office brachial BP (P ? 0.09). Similarly, 1
      standard deviation in SBP was significantly associated with 97.8 +/- 20.9, 86.4
      +/- 22.9, 74.1 +/- 23.3 and 51.3 +/- 22.6 in septum E/Ea and 68.6 +/- 2 0.1, 54.2
      +/- 21.9, 37.9 +/- 22.4 and 23.1 +/- 21.4 in lateral E/Ea, for office and 24-h
      aortic and brachial SBP, respectively. In qualitative analysis, except for office
      brachial BP, office aortic and 24-h brachial and aortic BPs were all
      significantly associated with LVDD (P ? 0.03), with the highest odds ratio in 24
      h aortic SBP. Furthermore, aortic BP, no matter in the office or 24-h ambulatory
      setting, showed the largest area under receiver operating characteristic curves
      (P ? 0.02). In conclusion, 24-h aortic BP is superior to other BPs in the
      association with LVDD.

PMID- 25391759
TI  - Correlation between baseline blood pressure and the brainstem FMRI response to
      isometric forearm contraction in human volunteers: a pilot study.
AB  - It has been shown previously that changes in brainstem neural activity correlate
      with changes in both mean arterial pressure (MAP) and muscle sympathetic nerve
      activity (MSNA) during static handgrip (SHG). However, the relationship between
      baseline MAP and brainstem neural activity is unclear. We investigated changes in
      blood oxygen level-dependent (BOLD) signal induced by SHG in 12 young adults
      using BOLD functional magnetic resonance imaging (FMRI). An estimation of the
      blood pressure response to SHG was obtained in seven subjects during a session
      outside the MRI scanner and was used to model the blood pressure response to SHG
      inside the scanner. SHG at 40% of maximum grip increased MAP (mean +/- s.d.) at
      the end of the 180-s squeeze from 85 +/- 6 mm Hg to 108 +/- 15 mm Hg, P = 0.0001.
      The brainstem BOLD signal change associated with SHG was localised to the
      ventrolateral medulla. This regional BOLD signal change negatively correlated
      with baseline MAP, r = -0.61, P = 0.01. This relationship between baseline MAP
      and brainstem FMRI responses to forearm contraction is suggestive of a possible
      role for brainstem activity in the control of MAP and may provide mechanistic
      insights into neurogenic hypertension.

PMID- 25391760
TI  - The emerging role of non-coding RNA in essential hypertension and blood pressure
      regulation.
AB  - Unravelling the complete genetic predisposition to high blood pressure (BP) has
      proven to be challenging. This puzzle and the fact that coding regions of the
      genome account for less than 2% of the entire human DNA support the hypothesis
      that genetic mechanism besides coding genes are likely to contribute to BP
      regulation. Non-coding RNAs (ncRNAs) are emerging as key players of transcription
      regulation in both health and disease states. They control basic functions in
      virtually all cell types relevant to the cardiovascular system and, thus, a
      direct involvement with BP regulation is highly probable. Here, we review the
      literature about ncRNAs associated with human BP and essential hypertension,
      highlighting investigations, methodology and difficulties arising in the field.
      The most investigated ncRNAs so far are microRNAs (miRNAs), small ncRNAs that
      modulate gene expression by posttranscriptional mechanisms. We discuss studies
      that have examined miRNAs associated with BP in biological fluids, such as blood
      and urine, and tissues, such as vascular smooth muscle cells and the kidney.
      Furthermore, we review the interaction between miRNA binding sites and single
      nucleotide polymorphisms in genes associated with BP. In conclusion, there is a
      clear need for more human and functional studies to help elucidate the
      multifaceted roles of ncRNAs, in particular mid- and long ncRNAs in BP
      regulation. 

PMID- 25391761
TI  - Resistance to recommending exercise in hypertension?

PMID- 25391762
TI  - Prevalence and predictors of resistance and aerobic exercise among hypertensive
      adults in the United States.

PMID- 25391763
TI  - Scrapie infection in experimental rodents and SMB-S15 cells decreased the brain
      endogenous levels and activities of Sirt1.
AB  - Prion diseases are composed of a group of fatal neurodegenerative disorders
      resulting from misfolding of cellular prion (PrP(C)) into scrapie prion
      (PrP(Sc)). Sirt1, a class III histone deacetylase, has been reported to protect
      neuronal cells against PrP (106-126)-induced cell death. To address the potential
      role of Sirt1 during prion infection, the levels and enzyme activities of Sirt1
      in the brains of scrapie-infected rodents, including hamsters infected with
      strain 263K, mice infected with strains 139A and ME7, and in prion infected SMB
      S15 cells, were analyzed. Western blots revealed that endogenous Sirt1 levels
      were significantly decreased in all tested scrapie-infected models. Dynamic
      assays of brain Sirt1 levels in 263K-infected hamsters during incubation period
      showed a time-dependent decrease. The acetylating forms of Sirt1 target proteins,
      P53, PGC-1, and STAT3, markedly increased both in the brains of scrapie-infected
      rodents and in SMB-S15 cells, representing decreased Sirt1 activity.
      Immunofluorescent assays illustrated that Sirt1 predominately localized in
      cytosol of SMB-S15 cells but clearly distributed in nucleus of its normal partner
      cell line, SMB-PS. Moreover, accompanying with increase of Sirt1 level and
      decrease of acetyl-P53 level, treatments with Sirt1 activators SRT1720 and
      resveratrol in SMB-S15 cells significantly reduced PrP(Sc); at the same time, the
      cellular distribution of PrP proteins became normal, and the cell proliferating
      state was slightly improved. These data indicate that prion infection notably
      attenuates the Sirt1 activity in host cells. Sensitivity of the PrP(Sc) to Sirt1
      activators highlights a potential role of Sirt1 in prion therapeutics. 

PMID- 25391764
TI  - Histone deacetylase inhibitor, trichostatin A, improves learning and memory in
      high-fat diet-induced cognitive deficits in mice.
AB  - Metabolic syndrome is increasingly recognized for its effects on cognitive
      health. Recent studies have highlighted the role of histone deacetylases (HDACs)
      in metabolic syndrome and cognitive functions. The present study was designed to
      investigate the possible therapeutic role of a HDAC inhibitor, trichostatin A
      (TSA), in cognitive impairment associated with metabolic syndrome. To ascertain
      the mechanisms involved, we fed mice with high-fat diet (HFD) for 4 weeks and
      examined changes in behavioral and biochemical/oxidative stress markers. Mice
      subjected to HFD exhibited characteristic features of metabolic disorder, viz.,
      hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and lower high-density
      lipoprotein (HDL) cholesterol levels. Moreover, these mice showed severe deficits
      in learning and memory as assessed by the Morris water maze and passive avoidance
      tasks along with elevated oxidative stress and inflammatory markers in brain
      homogenates. The observed changes occurred concurrently with reduced brain
      derived neurotrophic factor (BDNF). In contrast, the mice treated with the HDAC
      inhibitor, TSA (0.5 and 1 mg/kg, i.p.), showed a significant and dose-dependent
      reduction in serum glucose, triglycerides, and total cholesterol along with
      improvement in HDL-cholesterol levels and learning and memory performance. TSA
      treatment also results in alleviation of oxidative stress and neuroinflammatory
      markers. Moreover, TSA significantly augmented the BDNF levels in HFD-fed mice.
      Thus, based upon these observations, it may be suggested that HDAC inhibition
      could be a novel therapeutic strategy to combat cognitive impairment associated
      with metabolic syndrome.

PMID- 25391765
TI  - Predictors of liver-related death among people who inject drugs in Vancouver,
      Canada: a 15-year prospective cohort study.
AB  - INTRODUCTION: While HIV/AIDS remains an important cause of death among people who
      inject drugs (PWID), the potential mortality burden attributable to hepatitis C
      virus (HCV) infection among this population is of increasing concern. Therefore,
      we sought to identify trends in and predictors of liver-related mortality among
      PWID. METHODS: Data were derived from prospective cohorts of PWID in Vancouver,
      Canada, between 1996 and 2011. Cohort data were linked to the provincial vital
      statistics database to ascertain mortality rates and causes of death.
      Multivariate Cox proportional hazards regression was used to examine the
      relationship between HCV infection and time to liver-related death. A sub
      analysis examined the effect of HIV/HCV co-infection. RESULTS AND DISCUSSION: In
      total, 2,279 PWID participated in this study, with 1,921 (84.3%) having
      seroconverted to anti-HCV prior to baseline assessments and 124 (5.4%) during
      follow-up. The liver-related mortality rate was 2.1 (95% confidence interval
      [CI]: 1.5-3.0) deaths per 1,000 person-years and was stable over time. In
      multivariate analyses, HCV seropositivity was not significantly associated with
      liver-related mortality (adjusted relative hazard [ARH]: 0.45; 95% CI: 0.15
      1.37), but HIV seropositivity was (ARH: 2.67; 95% CI: 1.27-5.63). In sub
      analysis, HIV/HCV co-infection had a 2.53 (95% CI: 1.18-5.46) times hazard of
      liver-related death compared with HCV mono-infection. CONCLUSIONS: In this study,
      HCV seropositivity did not predict liver-related mortality while HIV
      seropositivity did. The findings highlight the critical role of HIV mono- and co
      infection rather than HCV infection in contributing to liver-related mortality
      among PWID in this setting.

PMID- 25391766
TI  - Ageism and Autonomy in Health Care: Explorations Through a Relational Lens.
AB  - Ageism within the context of care has attracted increasing attention in recent
      years. Similarly, autonomy has developed into a prominent concept within health
      care law and ethics. This paper explores the way that ageism, understood as a set
      of negative attitudes about old age or older people, may impact on an older
      person's ability to make maximally autonomous decisions within health care. In
      particular, by appealing to feminist constructions of autonomy as relational, I
      will argue that the key to establishing this link is the concept of self
      relations such as self-trust, self-worth and self-esteem. This paper aims to
      demonstrate how these may be impacted by the internalisation of negative
      attitudes associated with old age and care. In light of this, any legal or policy
      response must be sensitive to and flexible enough to deal with the way in which
      ageism impacts autonomy.

PMID- 25391767
TI  - Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced
      acute lung injury.
AB  - Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has
      raised concern in China. Although most infections resulted in respiratory
      illness, some severe cases resulted in acute respiratory distress syndrome
      (ARDS), which is a severe form of acute lung injury (ALI) that further
      contributes to morbidity. To date, no effective drugs that improve the clinical
      outcome of influenza A (H7N9) virus-infected patients have been identified.
      Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies
      such as cardiovascular functions, renal disease, and acute lung injury. In the
      current study, we report that ACE2 could mediate the severe acute lung injury
      induced by influenza A (H7N9) virus infection in an experimental mouse model.
      Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by
      targeting the angiotensin II type 1 receptor (AT1). The current findings
      demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced
      acute lung injury, and suggest that might be a useful potential therapeutic
      target for future influenza A (H7N9) outbreaks. 

PMID- 25391768
TI  - Soluble overexpression and purification of bioactive human CCL2 in E. coli by
      maltose-binding protein.
AB  - Human chemokine (C-C motif) ligand 2 (hCCL2) is a small cytokine in the CC
      chemokine family that attracts monocytes, memory T lymphocytes, and natural
      killer cells to the site of tissue injury- or infection-induced inflammation.
      hCCL2 has been implicated in the pathogeneses of diseases characterized by
      monocytic infiltrates, including psoriasis, rheumatoid arthritis,
      atherosclerosis, multiple sclerosis, and insulin-resistant diabetes. The
      prokaryotic overexpression of hCCL2 has been investigated previously in an
      attempt to develop biomedical applications for this factor, but this has been
      hampered by protein misfolding and aggregation into inclusion bodies. In our
      present study, we screened 7 protein tags-Trx, GST, MBP, NusA, His8, PDI, and
      PDIb'a'-for their ability to allow the soluble overexpression of hCCL2. Three
      tags-MBP, His8, and PDI-solubilized more than half of the expressed hCCL2 fusion
      proteins. Lowering the expression temperature to 18  degrees C significantly
      further improved the solubility of all fusion proteins. MBP was chosen for
      further study based on its solubility, expression level, ease of purification,
      and tag size. MBP-CCL2 was purified using conventional chromatography and cleaved
      using TEV or Factor Xa proteases. Biological activity was assessed using
      luciferase and cell migration assays. Factor Xa-cleaved hCCL2 was found to be
      active and TEV-cleaved hCCL2 showed relatively less activity. This is probably
      because the additional glycine residues present at the N-terminus of hCCL2
      following TEV digestion interfere with the binding of hCCL2 to its receptor. 

PMID- 25391769
TI  - Frequency of interleukin 28B rs12979860 C>T variants in Filipino patients
      chronically infected with hepatitis B virus.
AB  - Hepatitis B virus (HBV) is one of the most prevalent viral infections worldwide.
      Nearly 400 million individuals are chronic carriers of HBV. The aim of the
      present study was to determine the frequency of human interleukin 28B (IL28B)
      variants among treatment naive Filipino patients clinically diagnosed with
      chronic hepatitis B (CHB), and to compare the IL28B frequency distribution with
      various ethnic populations. Fifty-seven CHB patients and 43 normal controls were
      enrolled in this study. Real-time PCR was performed using the TaqMan genotyping
      assay for IL28B rs12979860. The allelic frequencies among normal controls were
      0.94 and 0.06 for the IL28B rs12979860 C and T alleles, respectively. Eighty
      eight percent were identified as homozygous for the IL28B C/C genotype and 12%
      were identified as heterozygous for the IL28B C/T genotype. Among CHB patients,
      the allelic frequencies were 0.90 for the IL28B C allele and 0.10 for the IL28B T
      allele. No IL28B T/T genotype was observed between the two groups. No significant
      difference in the distribution of IL28B genotypes was observed between normal
      controls and CHB patients. Allelic frequencies of IL28B among Filipinos were
      similar with other Asian populations but significantly different from Caucasians.
      The frequency of rs12979860 C>T variants among Filipino CHB patients has not yet
      been reported. These data provided new insight into the geographical frequency
      distribution of IL28B variants. Further studies are needed to determine the
      possible association between IL28B variants and response to pegylated-interferon
      alpha plus ribavirin combination therapy among Filipino patients chronically
      infected with HBV.

PMID- 25391770
TI  - Selection of reference genes for quantitative real time RT-PCR during dimorphism
      in the zygomycete Mucor circinelloides.
AB  - Mucor circinelloides is a dimorphic fungal model for studying several biological
      processes including cell differentiation (yeast-mold transitions) as well as
      biodiesel and carotene production. The recent release of the first draft sequence
      of the M. circinelloides genome, combined with the availability of analytical
      methods to determine patterns of gene expression, such as quantitative Reverse
      transcription-Polymerase chain reaction (qRT-PCR), and the development of
      molecular genetic tools for the manipulation of the fungus, may help identify M.
      circinelloides gene products and analyze their relevance in different biological
      processes. However, no information is available on M. circinelloides genes of
      stable expression that could serve as internal references in qRT-PCR analyses.
      One approach to solve this problem consists in the use of housekeeping genes as
      internal references. However, validation of the usability of these reference
      genes is a fundamental step prior to initiating qRT-PCR assays. This work
      evaluates expression of several constitutive genes by qRT-PCR throughout the
      morphological differentiation stages of M. circinelloides; our results indicate
      that tfc-1 and ef-1 are the most stable genes for qRT-PCR assays during
      differentiation studies and they are proposed as reference genes to carry out
      gene expression studies in this fungus. 

PMID- 25391771
TI  - Serum microRNAs; miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p could be used
      as novel non-invasive biomarkers for HCV-positive cirrhosis and hepatocellular
      carcinoma.
AB  - Recently, serum miRNAs have been evolved as possible biomarkers for different
      diseases including hepatocellular carcinoma and other types of cancers.
      Investigating certain serum miRNAs as novel non-invasive markers for early
      detection of HCV-positive cirrhosis and hepatocellular carcinoma (HCC). The
      expression profiles of 58 miRNA were analyzed in patient's plasma of chronic
      hepatitis C (CHC), HCV-positive cirrhosis and HCV-positive HCC and compared with
      control group samples. Totally 94 plasma samples; 64 patient plasma (26 CHC, 30
      HCV-positive cirrhosis, 8 HCV-positive HCC) and 28 control group plasma, were
      included. The expression profiles of 58 miRNAs were detected for all patient and
      control group plasma samples by qRT-PCR using BioMarkTM 96.96 Dynamic Array
      (Fluidigm Corporation) system. In CHC group, expression profiles of miR-30a-5p,
      miR-30c-5p, miR-206 and miR-302c-3p were found significantly deregulated (p <
      0.05) when compared versus control group. In HCV-positive cirrhosis group,
      expression profiles of miR-30c-5p, miR-223-3p, miR-302c-3p, miR-17-5p, miR-130a
      3p, miR-93-5p, miR-302c-5p and miR-223-3p were found significantly deregulated (p
      < 0.05). In HCV-positive HCC group, expression profiles of miR-17-5p, miR-223-3p
      and miR-24-3p were found significant (p < 0.05). When all groups were compared
      versus control, miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p were found
      significantly deregulated for cirrhosis and HCC. These results imply that miR-30c
      5p, miR-223-3p, miR-302c-3p and miR-17-5p could be used as novel non-invasive
      biomarkers of HCV-positive HCC in very early, even at cirrhosis stage of liver
      disease. 

PMID- 25391772
TI  - Two novel polymorphisms of bovine SIRT2 gene are associated with higher body
      weight in Nanyang cattle.
AB  - Identification of polymorphisms associated with economic traits is important for
      successful marker-assisted selection in cattle breeding. The family of mammalian
      sirtuin regulates many biological functions, such as life span extension and
      energy metabolism. SIRT2, a most abundant sirtuin in adipocytes, acts as a
      crucial regulator of adipogenic differentiation and plays a key role in
      controlling adipose tissue function and mass. Here we investigated single
      nucleotide polymorphisms (SNPs) of bovine SIRT2 in 1226 cattle from five breeds
      and further evaluated the effects of identified SNPs on economically important
      traits of Nanyang cattle. Our results revealed four novel SNPs in bovine SIRT2,
      one was located in intronic region and the other three were synonymous mutations.
      Linkage disequilibrium and haplotype analyses based on the identified SNPs showed
      obvious difference between crossbred breed and the other four beef breeds.
      Association analyses demonstrated that SNPs g.17333C > T and g.17578A > G have a
      significantly effect on 18-months-old body weight of Nanyang population. Animals
      with combined genotype TTGG at the above two loci exhibited especially higher
      body weight. Our data for the first time demonstrated that polymorphisms in
      bovine SIRT2 are associated with economic traits of Nanyang cattle, which will be
      helpful for future cattle selection practices. 

PMID- 25391773
TI  - Polymorphisms in nucleotide excision repair genes and susceptibility to
      colorectal cancer in the Polish population.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive disease that is
      associated with a severe deficiency in nucleotide excision repair. Genetic
      polymorphisms in XP genes may be associated with a change in DNA repair capacity,
      which could be associated with colorectal cancer development. We assessed the
      association between 94 single nucleotide polymorphisms (SNPs) within seven XP
      genes (XPA-XPG) and the colorectal cancer risk in the Polish population. We
      genotyped 758 unselected patients with colorectal cancer and 1,841 healthy
      adults. We found that a significantly decreased risk of colorectal cancer was
      associated with XPC polymorphism rs2228000_CT genotype (OR 0.59; p < 0.0001) and
      the rs2228000_TT genotype (OR 0.29; p < 0.0001) compared to the reference
      genotype (CC). And an increased disease risk was associated with the XPD SNP,
      rs1799793_AG genotype (OR 1.44, p = 0.018) and rs1799793_AA genotype (OR 3.31, p
      < 0.0001) compared to the reference genotype. Haplotype analysis within XPC, XPD
      and XPG revealed haplotypes associated with an altered colorectal cancer risk.
      Stratified analysis by gender showed differences between the association of three
      SNPs: XPC rs2228000, XPD rs1799793 and XPD rs238406 in females and males.
      Association analysis between age of disease onset and polymorphisms in XPD
      (rs1799793) and XPC (rs2228000) revealed differences in the prevalence of these
      variants in patients under and over 50 years of age. Our results confirmed that
      polymorphisms in XPC and XPD may be associated with the risk of colorectal
      cancer. 

PMID- 25391774
TI  - Recurrent intractable hiccups treated by cervical phrenic nerve block under
      electromyography: report of a case.
AB  - Intractable or persistent hiccups require intensive or invasive treatments. The
      use of a phrenic nerve block or destructive treatment for intractable hiccups has
      been reported to be a useful and discrete method that might be valuable to
      patients with this distressing problem and for whom diverse management efforts
      have failed. We herein report a successful treatment using a removable and
      adjustable ligature for the phrenic nerve in a patient with recurrent and
      intractable hiccups, which was employed under the guidance of electromyography. 

PMID- 25391775
TI  - [Investigation of prognostic factors for occult inguinal lymph node metastasis in
      penile cancer patients with no palpable or visibly enlarged inguinal lymph node
      (cN0)].
AB  - We investigated the incidence of inguinal lymph node metastasis in 66 penile
      cancer patients with no palpable or visibly enlarged inguinal lymph nodes (cN0).
      Median follow up interval was 35. 7 months. During follow up, 14 patients (21.2%)
      had inguinal lymph node metastasis and 6 patients died of cancer. Five-year
      disease-free survival was 77.3%. Univariate analysis demonstrated that local
      tumor staging (T), differentiation, lymphovascular invasion (LVI), and tumor
      infiltration pattern (INF, Yamamoto-Kohama grading system) were associated with
      the incidence of inguinal lymphnode metastasis. Multivariate analysis
      demonstrated that only LVI was associated with incidence of inguinal lymph node
      metastasis (p = 0.008, Hazard ratio 17.947). According to EAU risk
      classification, the incidence of inguinal lymph node metastasis in the low-risk
      group, intermediate risk group and high-risk group was 12.0, 17.6 and 55.6%,
      respectively. In conclusion, LVI is an independent prognostic factor for inguinal
      lymph node metastasis in cN0 penile cancer. Furthermore, EAU risk classification
      is valid judging from our cases and in incidence of inguinal lymph node
      metastasis. Either sentinel node biopsy or inguinal lymph node dissection is
      recommended in high and intermediate risk patient.

PMID- 25391776
TI  - [Gastric metastasis from renal cell carcinoma: two case reports].
AB  - Gastric metastasis from renal cell carcinoma (RCC) is a very rare event and
      treatment for such patients has not been established. We report two cases of
      gastric metastasis from RCC. The first case was in a 67- year-old man with a past
      history of right radical nephrectomy for RCC (ypT3aN0M0) six years ago. The whole
      body computed tomography (CT) revealed multiple lung nodules. We performed
      gastrointestinal endoscopy to find the primary lesion, and detected multiple
      submucosal tumors in the gastric body. Needle biopsy of these tumors revealed
      gastric metastasis from RCC. Oral sorafenib tosylate therapy was started. Twenty
      months later, gastrointestinal endoscopy showed only gastric erosion without
      malignant evidence. The second case was in a 70-year-old man complaining of
      epigastralgia. He had undergone right partial nephrectomy for RCC (pT1aN0M0) six
      years ago, and thoracoscopic wedge resection of a solitary lung nodule one year
      ago. Gastrointestinal endoscopy detected a solitary hyperplastic polyp in the
      anterior wall of the gastric body. Needle biopsy of this polyp revealed gastric
      metastasis from RCC. We performed laparoscopic partial gastrectomy.
      Gastrointestinal endoscopy and CT showed no evidence of metastasis or recurrence
      for 14 months after gastrectomy. 

PMID- 25391777
TI  - [A case of late perirenal fat recurrence after partial nephrectomy for T1A renal
      cell carcinoma].
AB  - An 84-year-old man had undergone laparoscopic partial nephrectomy for right renal
      cell carcinoma (RCC), cT1aN0M0 in 2003. The histopathological diagnosis was clear
      cell carcinoma, grade 1, v (-), surgical margin negative, pT1a. Nine years and 10
      months postoperatively, computed tomography scans demonstrated tumors on right
      renal fossa. As we could not detect other metastatic lesions, we diagnosed him
      with local recurrence of RCC and planned the surgery with curative intent. He
      underwent laparoscopic resection of retroperitoneal tumors. The histopathological
      diagnosis was clear cell carcinoma, grade 2 > 3, v (-), surgical margin negative,
      and confirmed recurrence of RCC. In retrospective review of 176 cases of pT1a
      renal cell carcinoma with partial nephrectomy in our institute, 3 patients (1.7%)
      developed local recurrence and 2 patients (1.1%) developed late local recurrence.

PMID- 25391778
TI  - [An infected renal cyst communicating with the urinary tract: a case report].
AB  - A 36-year-old man presented with fever and right backache. Abdominal computed
      tomographic scan revealed a right renal cyst, with a maximum diameter of 12 cm,
      and surrounded by a hyperdense area of perirenal fat tissue. The cyst appeared to
      be infected. Accordingly, we performed a percutaneous puncture of this cyst, and
      drained the fluid. The brown and cloudy fluid gradually became clear, the fluid
      volume increased a few days after the drainage. A communication between the
      infected cyst and urinary tract was suspected ; retrograde pyelography confirmed
      the presence of fistulas. The urine was drained, > 600 ml per day, for four
      weeks. Surgical resection of the cyst wall and closure of the fistulas were
      performed as an additional treatment. A year after the open surgical procedure,
      the renal cyst did not recur, and his renal function has been normal. 

PMID- 25391779
TI  - [Seroma formation associated with expanded polytetrafluoroethylene graft used for
      dialysis access: a case report].
AB  - The patient was a 67-year-old man with end stage renal failure. Hemodialysis had
      been started in 1998. An expanded polytetrafluoroethylene (PTFE) graft was
      inserted into his left forearm and used for vascular access. He received a
      partial replacement of the expanded PTFE graft in September 2013. A seroma formed
      after this intervention and subsequently grew larger. He thus underwent seroma
      removal and bypass graft surgery. Four months after the surgery, to date, he
      remains free of seroma recurrence. 

PMID- 25391780
TI  - [Laparoscopic resection of a retroperitoneal mullerian cyst: a case report].
AB  - A 51-year-old woman had a cystic mass in the retroperitoneal space, below the
      left kidney, which was incidentally detected at a medical check-up. The size of
      the mass was 6 cm in diameter, which was similar to that obtained by magnetic
      resonance imaging 4 years ago. We followed the case and found that the mass was
      slightly enlarged a year later. Because malignancy could not be ruled out, we
      performed a laparoscopic tumor excision. Histologically, the cyst was diagnosed
      as a Mullerian cyst, and there was no evidence of malignancy. Retroperitoneal
      Mullerian cyst is a rare tumor. Sixteen cases have been reported previously and
      this is the fourth case of a laparoscopic excision. 

PMID- 25391781
TI  - [A case of vesicovaginal fistula repair with rectus abdominus myofascial
      interposition flap after radical hysterectomy and radiation therapy].
AB  - Vesicovaginal fistulas (VVFs) caused after radiation are difficult to repair and
      require interposition of non-irradiated, well-vascularized tissue between urinary
      bladder and vagina. A 48-year-old female suffered cervical cancer and underwent
      radical hysterectomy followed by radiation therapy which caused VVF. The initial
      surgical repair performed 3 months after development of VVF, was unsuccessful
      because of the absence of peritoneum or omentum to interpose between urinary
      bladder and vagina probably due to history of cesarean section and radical
      hysterectomy. The second surgical repair was performed 15 months after the first
      surgery utilizing a rectus abdominus myofascial (RAM) interposition flap. Fifteen
      months after the second operation, she remains free from incontinence. This case
      suggests that RAM is useful even for postradiation VVF. 

PMID- 25391782
TI  - [Complete atrioventricular block due to cardiac metastasis from bladder cancer:
      case report].
AB  - A 72-year-old woman was diagnosed with bladder cancer (cT3bN0M0). After 2 cycles
      of GC (gemcitabine,cisplatin) neoadjuvant chemotherapy, the patient underwent a
      cystectomy and ileal conduit construction. Pathological findings showed
      urothelial carcinoma, high grade, G2>G3, pT3a, INFbeta, ly0, v1. Six months after
      the operation, metastases to the liver, lung, left adrenal gland, rib, multiple
      lymph nodes, and peritoneum were revealed. Under palliative care, she suffered
      from palpitation and general fatigue. Electrocardiogram findings showed a
      complete atrioventricular block, while echocardiography and computed tomography
      revealed cardiac metastasis. We diagnosed her with complete atrioventricular
      block due to cardiac metastasis from bladder cancer. She died 7 days after onset
      of the complete atrioventricular block without use of a pacemaker. 

PMID- 25391783
TI  - [A case of lymphoepithelioma-like carcinoma of the bladder].
AB  - Lymphoepithelioma-like carcinoma (LELC) of the bladder is very rare and only a
      few cases have been reported so far. Here, we report a case of LELC of the
      bladder with distant metastasis. A 73-year-old man presented with macroscopic
      hematuria and miction pain. Cystoscopy revealed non-papillary tumor and tissue
      biopsy was performed. Histopathological examination showed pure type of LELC in
      the bladder. Fludeoxyglucose positron emission tomography revealed lymph node
      metastasis. The tumor progressed rapidly and the patient died 4 months later.
      Although the prognosis of pure type of LELC has been reported to be good, our
      case indicates that the prognosis of pure type with distant metastasis may be
      poor. 

PMID- 25391784
TI  - [A case of bladder cancer arising after augmentation cystoplasty using ileal
      patch for interstitial cystitis].
AB  - A 62-year-old man, who was refractory to repeated hydrodistentions for
      interstitial cystitis, underwent augmentation cystoplasty using ileal patch.
      Pathological examination revealed no malignancy. Computed tomography (CT) scan
      showed multiple pelvic and para-aortic lymph-node swellings at 14 months after
      the operation. CT-guided lymph-nodes biopsies and transurethral bladder biopsies
      revealed invasive urothelial carcinoma with lymph node metastasis. In patients
      with symptoms of interstitial cystitis, bladder cancer should be kept in mind
      despite negative findings of cytology and bladder biopsies. 

PMID- 25391785
TI  - [Small cell carcinoma of the prostate effectively treated for relatively long
      term: a case report].
AB  - A 72-year-old Japanese man was referred to a hospital because of urinary
      retention. Digital rectal examination revealed a stony, hard nodule in the
      prostate. A high level of serum PSA was not detected. Prostatic biopsy was
      performed, and pathological examination indicated adenocarcinoma of the prostate.
      He was referred to our hospital for treatment. Imaging examinations revealed no
      metastases (T4N0M0), so we re-evaluated the biopsy specimens. Immunohistochemical
      examination revealed prostatic small cell carcinoma. His levels of neuron
      specific enolase (NSE) and pro-gastrin-releasing peptide (Pro-GRP) were high. We
      treated him with combination chemotherapy comprising irinotecan and cisplatin,
      and the treatment was effective. After four courses of the chemotherapy, levels
      of NSE and Pro-GRP had decreased, and the prostatic mass had decreased in size.
      Needle rebiopsy of the prostate demonstrated no evidence of malignancy. Adjuvant
      external beam radiation therapy was also performed. The patient iss till alive at
      18 month after diagnosis with no evidence of relapse or metastasis of the
      disease.

PMID- 25391786
TI  - [Metastatic tumor of the spermatic cord from gastric cancer: a case report].
AB  - A 66-year-old man presented with a painless swelling of left scrotal contents. We
      performed left inguinal orchiectomy and left inguinal lymphnode dissection.
      Histopathological examination revealed spermatic cord metastases from gastric
      carcinoma. We collected 44 cases of metastatic tumor of the spermatic cord from
      gastric cancer in the Japanese literature. 

PMID- 25391787
TI  - Occupational health physicians have better work conditions for handling sickness
      certification compared with general practitioners: results from a nationwide
      survey in Sweden.
AB  - AIMS: To study whether occupational health physicians (OPs) have a better work
      situation regarding handling of sickness certification compared with other
      physicians, in particular general practitioners (GPs), and to analyze
      associations between OPs' experiences of assessing and providing a long-term
      prognosis of patients' work capacity and some potentially interrelated factors.
      METHODS: Answers to a nationwide survey from physicians who had sickness
      certification consultations at least once monthly were analyzed. Differences
      among OPs (n=481), GPs (n=4257) and physicians working in other clinical settings
      (n=9452) were estimated by chi square tests. Associations between OPs'
      experiences as above and potentially interrelated factors were estimated using
      logistic regression analyses. RESULTS: Among OPs, a lower proportion experienced
      clinical work situations related to sickness certifications as 'very
      problematic', compared with the other physicians, and especially so compared with
      GPs. A higher proportion of OPs also had organizational support for handling
      sickness certifications. For OPs, experience of sickness certification
      consultations as problematic once a month or less often, not experiencing
      sickness certification tasks as a work environment problem, and having a well
      established workplace policy regarding sickness certification matters were
      significantly positively associated with finding assessing and providing a long
      term prognosis of work capacity as 'not at all/somewhat problematic'.
      CONCLUSIONS: OPs' work situation regarding sickness certifications was favorable
      compared with that of other physicians, and especially compared with that of GPS.
      Our results underline the importance of organizational support for ensuring
      physicians' experience of having professional competence in handling assessments
      of patients' work capacity.

PMID- 25391788
TI  - Interpersonal violence and overweight in adolescents: the HUNT Study.
AB  - AIMS: Overweight and obesity in children and adolescents are major public health
      challenges associated with psychosocial adversity and unfavourable lifestyle.
      Exposure to interpersonal violence, such as sexual abuse, violence and bullying,
      could represent precursors, accelerating or sustaining factors. METHODS: The
      Young-HUNT 3 study, 2006-2008, is a population-based, cross-sectional, cohort
      study of Norwegian youth that includes self-report data on exposure to
      interpersonal violence; pubertal status and timing; socioeconomic, psychosocial,
      and lifestyle factors; and clinical anthropometric measures. A cohort of 10,464
      adolescents aged 12-20 years from Nord-Trondelag County were invited to
      participate. Body mass index served as the outcome in the simple and multiple
      linear regression analyses. RESULTS: The response rate was 72.3% (7564), and
      49.9% (3777) of the respondents were girls. A robust and significant relationship
      between interpersonal violence and increased BMI for both genders was found.
      Importantly, interpersonal violence remained significantly correlated with higher
      BMI following adjustment for pubertal development, socioeconomic and psychosocial
      adversity and unfavourable lifestyle factors in both genders, although most
      evident in girls. Adjusted regression coefficients (95% confidence intervals) for
      the relationship between interpersonal violence and BMI were 0.33 (0.01, 0.65)
      for 1 type and 0.89 (0.37, 1.41) for 2 types, compared to no exposure in girls,
      and 0.40 (0.09, 0.71) for 1 type and 0.35 (-0.09, 0.79) for 2 types of
      interpersonal violence in boys. CONCLUSIONS: The empirical evidence of consistent
      associations between interpersonal violence, related psychosocial and lifestyle
      factors, and body fatness, indicates that these features play important roles for
      adolescents struggling with overweight.

PMID- 25391789
TI  - [Comparison of IOL-Master 500 vs. Lenstar LS900 concerning the calculation of
      target refraction: A retrospective analysis].
AB  - BACKGROUND: The choice of a suitable intraocular lens (IOL) and the calculation
      of postoperative refractive error is one of the most intriguing challenges of
      modern cataract surgery. This clinical trial compared the accuracy of two laser
      assisted optical biometers, the IOL-Master 500 (Carl Zeiss Meditec, Jena,
      Germany) and the Lenstar LS900 (Haag-Streit, Bern, Switzerland) without taking
      the postoperative results into consideration. MATERIAL AND METHODS: Artificial
      lenses (Alcon Pharma) for 114 eyes of 67 patients were measured using both
      biometric instruments. The deviation of the presumed refractive error from the
      desired preoperative refractive target was calculated with different formulae
      (i.e. SRK/T, HofferQ, Haigis and SRKII) based on the intraoperatively chosen IOL.
      The differences between both instruments were compared using Student's t-test.
      RESULTS: Using the SRKII formula a mean difference between the IOL-Master and the
      Lenstar of 0.07 D (p = 0.002) was calculated for 95 eyes, SRK/T used on 47 eyes
      showed a difference of 0.04 D (p = 0.27), HofferQ measured 0.09 D (p = 0.0001)
      between both instruments for 88 eyes and the Haigis formula also showed a mean
      difference of 0.09 D (p = 0.001) based on the calculations of 106 eyes.
      CONCLUSION: Both instruments gave reproducible and accurate results with only a
      small deviation from the desired target refraction and can therefore be
      considered as comparable for the calculation of IOLs. Statistically significant
      differences in the results were found when using the SRKII, HofferQ and Haigis
      formulae but these were too low to have any influence on the choice of IOL to be
      implanted.

PMID- 25391790
TI  - Bone quality assessment for total hip arthroplasty with intraoperative trabecular
      torque measurements.
AB  - BACKGROUND: In cases of poor bone quality, intraoperative torque measurement
      might be an alternative to preoperative dual-energy X-ray absorptiometry (DXA) to
      assess bone quality in total hip arthroplasty (THA). METHODS: Trabecular peak
      torque measurement was applied in 14 paired fresh frozen human femurs. Here, a
      6.5 * 23 mm wingblade was inserted into the proximal femur without harming the
      lateral cortical bone. Further tests of the proximal femur also evaluated bone
      strength (DXA, micro-computed tomography (MUCT), monoaxial compression test), and
      the results were compared to the trabecular torque measurement. Student's t-test
      was used to compare the values of the groups. Pearson product-moment was applied
      to correlate the values of the peak torque measurement with the bone strength
      measured by DXA, MUCT, and monoaxial compression test. RESULTS: In the femoral
      head, the mean trabecular peak torque was 4.38 +/- 1.86 Nm. These values showed a
      strong correlation with the values of the DXA, the MUCT, and the biomechanical
      load test (Pearson's product-moment: DXA: 0.86, MUCT-BMD: 0.80, load test: 0.85).
      Furthermore, the torque measurement showed a more pronounced correlation with the
      biomechanical load test compared to the DXA. CONCLUSIONS: The use of this method
      provides highly diagnostic information about bone quality. Since the approach was
      adjusted for THA, no harm of the lateral bone stock will result from this
      measurement during surgery. The results of this initial study employing small
      sample sizes indicate that this new method is as sensitive as DXA in predicting
      bone quality and may function as an intraoperative alternative to DXA in THA.
      Nevertheless, before this method will turn into clinical use, more research and
      clinical trials are necessary.

PMID- 25391791
TI  - The physical basis of total internal reflection fluorescence (TIRF) microscopy
      and its cellular applications.
AB  - Total internal reflection fluorescence (TIRF) microscopy has gained popularity in
      recent years among cell biologists due to its ability to clearly visualize events
      that occur at the adherent plasma membrane of cells. TIRF microscopy systems are
      now commercially available from nearly all microscope suppliers. This review aims
      to give the reader an introduction to the physical basis of TIRF and
      considerations that need to be made when purchasing a commercial system. We
      explain how TIRF can be combined with other microscopy modalities and describe
      how to use TIRF to study processes such as endocytosis, exocytosis, and focal
      adhesion dynamics. Finally, we provide a step-by-step guide to imaging and
      analyzing focal adhesion dynamics in a migrating cell using TIRF microscopy. 

PMID- 25391792
TI  - Two-photon excitation microscopy and its applications in neuroscience.
AB  - Two-photon excitation (2PE) overcomes many challenges in fluorescence microscopy.
      Compared to confocal microscopy, 2PE microscopy improves depth penetration, owing
      to the longer excitation wavelength required and to the ability to collect
      scattered emission photons as a useful signal. It also minimizes photodamage
      because lower energy photons are used and because fluorescence is confined to the
      geometrical focus of the laser spot. 2PE is therefore ideal for high-resolution,
      deep-tissue, time-lapse imaging of dynamic processes in cell biology. Here, we
      provide examples of important applications of 2PE for in vivo imaging of neuronal
      structure and signals; we also describe how it can be combined with optogenetics
      or photolysis of caged molecules to simultaneously probe and control neuronal
      activity. 

PMID- 25391793
TI  - Live spheroid formation recorded with light sheet-based fluorescence microscopy.
AB  - We provide a detailed protocol for a three-dimensional long-term live imaging of
      cellular spheroids with light sheet-based fluorescence microscopy. The protocol
      allows the recording of all phases of spheroid formation in three dimensions,
      including cell proliferation, aggregation, and compaction. We employ the human
      hepatic cell line HepaRG transfected with the fusion protein H2B-GFP, i.e., a
      fluorescing histone. The protocol allows monitoring the effect of drugs or
      toxicants. 

PMID- 25391794
TI  - Fluorescence microscopy-based RNA interference screening.
AB  - Using RNAi interference (RNAi), it is possible to study the effect of specific
      gene knockdowns in mammalian cells. In this protocol we present the automated
      preparation of "ready to transfect" multiwell plates and cell arrays, on which
      cells can be grown which are then reversely transfected with one type of siRNA in
      every individual well or spot. Additionally, different microscope types for
      screening approaches are compared and considerations about the information
      workflow are made.

PMID- 25391795
TI  - Fluorescence resonance energy transfer microscopy (FRET).
AB  - FRET (Forster Resonance Energy Transfer) microscopy breaks the resolution limit
      of light to let us investigate the conformation and function of proteins within
      living cells. Intensity-based methods are the most popular and direct approach to
      detect FRET. Among them, detection of sensitized emission signals and ratio
      imaging of specially designed FRET sensors are routinely used in modern cell
      biology laboratories. In this chapter, we provide protocols for both these
      techniques. We guide the reader through the mathematical corrections necessary to
      calculate the sensitized emission image. We illustrate this approach with an
      example of studying the interaction of nexin (SNX1) proteins. In the ratio FRET
      protocol, we focus on monitoring changes in cellular concentration of cAMP with
      an EPAC-based FRET sensor.

PMID- 25391796
TI  - Localizing protein-protein interactions in living cells using fluorescence
      lifetime imaging microscopy.
AB  - In the past decade, advances in fluorescence lifetime imaging have extensively
      applied in the life sciences, from fundamental biological investigations to
      advanced clinical diagnosis. Fluorescence lifetime imaging microscopy (FLIM) is
      now routinely used in the biological sciences to monitor dynamic signaling events
      inside living cells, e.g., Protein-Protein interactions. In this chapter, we
      describe the calibration of both time-correlated single-photon counting (TCSPC)
      and frequency domain (FD) FLIM systems and the acquisition and analysis of FLIM
      FRET data for investigating Protein-Protein interactions in living cells. 

PMID- 25391797
TI  - Analysis of biomolecular dynamics by FRAP and computer simulation.
AB  - We present a Monte Carlo simulation environment for modelling complex biological
      molecular interaction networks and for the design, validation, and quantitative
      analysis of FRAP assays to study these. The program is straightforward in its
      implementation and can be instructed through an intuitive script language. The
      simulation tool fits very well in a systems biology research setting that aims to
      maintain an interactive cycle of experiment-driven modelling and model-driven
      experimentation: the model and the experiment are in the same simulation. The
      full program can be obtained by request to the authors. 

PMID- 25391798
TI  - Fluorescence correlation spectroscopy.
AB  - Fluorescence fluctuation spectroscopy techniques allow the quantification of
      fluorescent molecules present at the nanomolar concentration level. After a brief
      introduction to the technique, this chapter presents a protocol including
      background information in order to measure and quantify the molecular interaction
      of two signaling proteins inside the living cell using fluorescence cross
      correlation spectroscopy. 

PMID- 25391800
TI  - Practical structured illumination microscopy.
AB  - Structured illumination microscopy (SIM) is a method that can double the spatial
      resolution of wide-field fluorescence microscopy in three dimensions by using
      spatially structured illumination light. In this chapter, we introduce the basic
      principles of SIM and describe in detail several different implementations based
      on either a diffraction grating or liquid crystal spatial light modulators. We
      also describe nonlinear SIM, a method that in theory can achieve unlimited
      resolution. In addition, we discuss a number of key points important for high
      resolution imaging. 

PMID- 25391799
TI  - Homo-FRET imaging highlights the nanoscale organization of cell surface
      molecules.
AB  - Several models have been proposed to understand the structure and organization of
      the plasma membrane in living cells. Predicated on equilibrium thermodynamic
      principles, the fluid-mosaic model of Singer and Nicholson and the model of lipid
      domains (or membrane rafts) are dominant models, which account for a fluid
      bilayer and functional lateral heterogeneity of membrane components,
      respectively. However, the constituents of the membrane and its composition are
      not maintained by equilibrium mechanisms. Indeed, the living cell membrane is a
      steady state of a number of active processes, namely, exocytosis, lipid synthesis
      and transbilayer flip-flop, and endocytosis. In this active milieu, many lipid
      constituents of the cell membrane exhibit a nanoscale organization that is also
      at odds with passive models based on chemical equilibrium. Here we provide a
      detailed description of microscopy and cell biological methods that have served
      to provide valuable information regarding the nature of nanoscale organization of
      lipid components in a living cell.

PMID- 25391801
TI  - 4Pi microscopy of the nuclear pore complex.
AB  - 4Pi microscopy is a far-field fluorescence microscopy technique, in which the
      wave fronts of two opposing illuminating beams are adjusted to constructively
      interfere in a common focus. This yields a diffraction pattern in the direction
      of the optical axis, which essentially consists of a main focal spot accompanied
      by two smaller side lobes. At optimal conditions, the main peak of this so-called
      point spread function has a full width at half maximum: fixed phrase of 100 nm in
      the direction of the optical axis, and thus is 6-7-fold smaller than that of a
      confocal microscope. In this chapter, we describe the basic features of 4Pi
      microscopy and its application to cell biology using the example of the nuclear
      pore complex, a large protein assembly spanning the nuclear envelope.

PMID- 25391802
TI  - Application of STED microscopy to cell biology questions.
AB  - The increasing interest in "seeing" the molecular environment in biological
      systems has led to the recent quest for breaking the diffraction barrier in far
      field fluorescence microscopy. The first nanoscopy method successfully applied to
      conventional biological probes was stimulated emission depletion microscopy
      (STED). It is based on a physical principle that instantly delivers diffraction
      unlimited images, with no need for further computational processing: the
      excitation laser beam is overlaid with a doughnut-shaped depleting beam that
      switches off previously excited fluorophores, thereby resulting in what is
      effectively a smaller imaging volume. In this chapter we give an overview of
      several applications of STED microscopy to biological questions. We explain
      technical aspects of sample preparation and image acquisition that will help in
      obtaining good diffraction-unlimited pictures. We also present embedding
      techniques adapted for ultrathin sectioning, which allow optimal 3D resolutions
      in virtually all biological preparations. 

PMID- 25391803
TI  - Three-dimensional photoactivated localization microscopy with genetically
      expressed probes.
AB  - Photoactivated localization microscopy (PALM) and related single-molecule imaging
      techniques enable biological image acquisition at ~20 nm lateral and ~50-100 nm
      axial resolution. Although such techniques were originally demonstrated on single
      imaging planes close to the coverslip surface, recent technical developments now
      enable the 3D imaging of whole fixed cells. We describe methods for converting a
      2D PALM into a system capable of acquiring such 3D images, with a particular
      emphasis on instrumentation that is compatible with choosing relatively dim,
      genetically expressed photoactivatable fluorescent proteins (PA-FPs) as PALM
      probes. After reviewing the basics of 2D PALM, we detail astigmatic and
      multiphoton imaging approaches well suited to working with PA-FPs. We also
      discuss the use of open-source localization software appropriate for 3D PALM. 

PMID- 25391804
TI  - Direct stochastic optical reconstruction microscopy (dSTORM).
AB  - Single-molecule localization-based super-resolution microscopy can be performed
      with regular, bright, and photostable organic fluorophores. We review a concept
      termed direct stochastic optical reconstruction microscopy (dSTORM), which
      operates conventional fluorophores as photoswitches and provides an optical
      resolution of ~20 nm. We introduce the principle of dSTORM, illustrate
      experimental schemes, and discuss approaches for data analysis.

PMID- 25391805
TI  - Optogenetics: optical control of a photoactivatable Rac in living cells.
AB  - Recent developments in optogenetics have extended optical control of signaling to
      intracellular proteins, including Rac, a small G protein in the Rho family. A
      blue light-sensing LOV (light, oxygen, or voltage) domain derived from Avena
      sativa (oat) phototropin was fused to the N-terminus of a constitutively active
      mutant of Rac, via an alpha-helix (Jalpha) that is conserved among plant
      phototropins. The fused LOV domain occluded binding of downstream effectors to
      Rac in the dark. Exposure to blue light caused a conformational change of the LOV
      domain and unwinding of the Jalpha helix, relieving steric inhibition. The LOV
      domain incorporates a flavin as the photon-absorbing cofactor and can be
      activated by light in a reversible and repeatable fashion. In cultured cells,
      global illumination with blue light rapidly activated Rac and led to cell
      spreading and membrane ruffling. Localized and pulsed illumination generated a
      gradient of Rac activity and induced directional migration. In this chapter, we
      will describe the techniques in detail and present some examples of applications
      of using photoactivatable Rac (PA-Rac) in living cells.

PMID- 25391806
TI  - Evaluation of 9 rapid diagnostic tests for screening HIV infection, in Lome,
      Togo.
AB  - PURPOSE: HIV rapid diagnostic tests (RDT) could be greatly contributive for a
      universal access to HIV diagnosis. However, according to the WHO, these tests
      need to be assessed before they can be used in routine. METHOD AND RESULTS: We
      assessed 9 RDT in routine clinical use between 2009 and 2013. The sensitivity and
      specificity observed for 7 tests were>=99% and>=98%, respectively: FIRST RESPONSE
      HIV1-2-O PMC Medical, India, GENIE Fast HIV 1-2 and GENIETM III HIV(1/2) Bio-Rad,
      France, HIV TRI-DOT+Ag;J. Mitra, INDIA; SD BIOLINE HIV(1/2) 3.0 and SD BIOLINE
      HIV/SYPHILIS DUO Standard Diagnostic, Korea; and VIKIA HIV(1/2); BioMerieux,
      France. Two tests had performances inferior to WHO recommendations: INSTI HIV1/2
      Biolytical Canada; sensitivity=97.8% and HEXAGON HIV HUMAN GmbH Germany;
      specificity=94.8%. CONCLUSION: Seven of 9 RDT had excellent performances.
      Nevertheless, they can be used only after training staff, and taking into account
      national algorithm for their safe use.

PMID- 25391807
TI  - Immobilization of Candida rugosa lipase onto an eco-friendly support in the
      presence of ionic liquid.
AB  - Candida rugosa lipase (CRL) was immobilized on an eco-friendly support poly(3
      hydroxybutyrate-co-hydroxyvalerate) (PHBV), by physical adsorption, using
      different ionic liquids (ILs) as immobilization additives. This was to
      investigate the influence of cationic core ([C4mpy]Cl, [C4min]Cl), of anions
      ([C4min]Cl, [C4min]N(CN)2, [C4min]Tf2N), and of cation chain length ([C2min]Tf2N,
      [C4min]Tf2N) in the immobilization process. The immobilized biocatalysts (IB)
      were characterized with respect to the morphological, physico-chemical
      properties, total activity recovery yield (Ya), and biochemical properties of
      more efficient IB were evaluated. Initially, it was found that the change of
      cationic core did not influence in Ya compared to the control. With change of
      anions, it was seen that the best result was obtained for the more hydrophobic
      anion (Tf2N), and finally increasing the cation chain length increased Ya. IB
      most efficient with [C4min]Tf2N obtained 78 % of Ya, more than twice the control
      value (30 %) and a considerable enhancement of operational stability compared
      with the control. 

PMID- 25391808
TI  - Effect of absorption recovery in bismuth-doped silica glass at 1450 nm on soliton
      grouping in fiber laser.
AB  - Saturable absorption in bismuth-doped glasses was found to have a noticeable
      influence on soliton interaction and group formation. This phenomenon, observed
      in 1450 nm mode-locked bismuth-doped fiber laser, shows the distinct feature of
      the multiple pulse regime, which appears as a stationary pulse group whose length
      can be spread over the whole cavity length by variation of the pump power and
      polarization. Pulse positioning within the ensemble depends on the saturation
      fluence and the relatively fast recovery dynamics of bismuth fiber.

PMID- 25391809
TI  - Rapid detection of single bacteria in unprocessed blood using Integrated
      Comprehensive Droplet Digital Detection.
AB  - Blood stream infection or sepsis is a major health problem worldwide, with
      extremely high mortality, which is partly due to the inability to rapidly detect
      and identify bacteria in the early stages of infection. Here we present a new
      technology termed 'Integrated Comprehensive Droplet Digital Detection' (IC 3D)
      that can selectively detect bacteria directly from milliliters of diluted blood
      at single-cell sensitivity in a one-step, culture- and amplification-free process
      within 1.5-4 h. The IC 3D integrates real-time, DNAzyme-based sensors, droplet
      microencapsulation and a high-throughput 3D particle counter system. Using
      Escherichia coli as a target, we demonstrate that the IC 3D can provide absolute
      quantification of both stock and clinical isolates of E. coli in spiked blood
      within a broad range of extremely low concentration from 1 to 10,000 bacteria per
      ml with exceptional robustness and limit of detection in the single digit regime.

PMID- 25391810
TI  - Genetic tools for the piezophilic hyperthermophilic archaeon Pyrococcus
      yayanosii.
AB  - The hyperthermophile Pyrococcus yayanosii CH1 is the only high-pressure-requiring
      microorganism obtained thus far within the archaea domain or among all non
      psychrophiles in any domain. In this study, we developed a genetic manipulation
      system for P. yayanosii after first isolating a facultatively piezophilic
      derivative strain, designated P. yayanosii A1. The 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase gene was overexpressed in strain P. yayanosii A1
      and was demonstrated to confer host cell resistance against simvastatin.
      Furthermore, using simvastatin as a selection marker, the endogenous pyrF of P.
      yayanosii A1 was disrupted through homologous recombination, thus generating the
      additional host strain P. yayanosii A2 (DeltapyrF). A markerless gene disruption
      vector was constructed by incorporating a pyrF-sim (R) cassette that enables the
      combined use of simvastatin resistance for positive selection and 5-FOA for
      counter selection. The utility of this versatile disruption system was
      demonstrated by deleting the carbon-nitrogen hydrolase of P. yayanosii strain A1.
      These results demonstrate that a variety of genetic tools are now in place to
      study unknown gene function and the molecular mechanisms of piezophilic
      adaptation in P. yayanosii. 

PMID- 25391811
TI  - Genetic data and de novo mutation rates in father-son pairs of 23 Y-STR loci in
      Southern Brazil population.
AB  - We evaluated haplotype and allele frequencies, as well as statistical forensic
      parameters, for 23 Y-chromosome short tandem repeats (STRs) loci of the
      PowerPlex(r)Y23 system (DYS19, DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392,
      DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, Y-GATA-H4,
      DYS481, DYS533, DYS549, DYS570, DYS576, DYS643) in a sample of 150 apparently
      healthy males, resident in South Brazil. A total of 150 different haplotypes were
      identified. The highest gene diversity (GD) was observed for the single locus
      marker DYS570 (GD = 0.7888) and for a two-locus system DYS385 (GD = 0.9009). We
      also examined 150 father-son pairs by the same system, and a total of 13
      mutations were identified in the 3450 father-son allelic transfers, with an
      overall mutation rate across the 23 loci of 3.768 * 10(-3) (95% CI: 3.542 * 10(
      3) to 3.944 * 10(-3)). In all cases there was only one locus mutated with
      gain/loss of repeats in the son (5 one-repeat gains, and 7 one-repeat and 1 two
      repeat losses); we observed no instances of mutations involving a non-integral
      number of repeats.

PMID- 25391812
TI  - Outcomes of abdominal radical trachelectomy: results of a multicenter prospective
      cohort study in a Tohoku Gynecologic Cancer Unit.
AB  - BACKGROUND: This study aimed to evaluate surgical, pregnancy, and prognostic
      outcomes of radical abdominal trachelectomy (RAT) for Japanese patients with
      early-stage cervical cancer. METHODS: This was a multicenter prospective cohort
      study conducted in member facilities of Tohoku Gynecologic Cancer Unit. Patients
      with FIGO 1A-1B1 squamous cell carcinoma were included. RESULTS: A total of 42
      patients were registered in this study, and all patients underwent planned RAT.
      The median stromal invasion and median horizontal spread of resected specimens
      were 4.6 (range 1.0-10.0) and 12.4 mm (range 3.0-28.0), respectively. The median
      surgical time and median blood loss were 304 min (range 233-611) and 848 mL
      (range 250-3984), respectively. Five patients (11.9 %) received blood
      transfusion. Five of 18 (27.8 %) patients who attempted to conceive achieved
      pregnancy, and 3 patients had healthy babies. However, all pregnancies required
      assisted reproductive technology with in-vitro fertilization and embryo transfer.
      Four patients (9.5 %) received postoperative adjuvant therapy, and 3 patients
      (7.1 %) developed disease recurrence. CONCLUSIONS: RAT may be safely performed
      for Japanese patients with FIGO 1A-1B1 squamous cell carcinoma of the cervix,
      even in educational medical facilities. However, less-invasive surgery should be
      considered more often to improve pregnancy outcomes.

PMID- 25391813
TI  - Profiling bacterial community in upper respiratory tracts.
AB  - BACKGROUND: Infection by pathogenic viruses results in rapid epithelial damage
      and significantly impacts on the condition of the upper respiratory tract, thus
      the effects of viral infection may induce changes in microbiota. Thus, we aimed
      to define the healthy microbiota and the viral pathogen-affected microbiota in
      the upper respiratory tract. In addition, any association between the type of
      viral agent and the resultant microbiota profile was assessed. METHODS: We
      analyzed the upper respiratory tract bacterial content of 57 healthy asymptomatic
      people (17 health-care workers and 40 community people) and 59 patients acutely
      infected with influenza, parainfluenza, rhino, respiratory syncytial, corona,
      adeno, or metapneumo viruses using culture-independent pyrosequencing. RESULTS:
      The healthy subjects harbored primarily Streptococcus, whereas the patients
      showed an enrichment of Haemophilus or Moraxella. Quantifying the similarities
      between bacterial populations by using Fast UniFrac analysis indicated that
      bacterial profiles were apparently divisible into 6 oropharyngeal types in the
      tested subjects. The oropharyngeal types were not associated with the type of
      viruses, but were rather linked to the age of the subjects. Moraxella
      nonliquefaciens exhibited unprecedentedly high abundance in young subjects aged
      <6 years. The genome of M. nonliquefaciens was found to encode various proteins
      that may play roles in pathogenesis. CONCLUSIONS: This study identified 6
      oropharyngeal microbiome types. No virus-specific bacterial profile was
      discovered, but comparative analysis of healthy adults and patients identified a
      bacterium specific to young patients, M. nonliquefaciens.

PMID- 25391814
TI  - Effects of psyllium on LDL-cholesterol concentrations in Brazilian children and
      adolescents: a randomised, placebo-controlled, parallel clinical trial.
AB  - The present study investigated the LDL-cholesterol (LDL-C)-lowering effects of
      psyllium in Brazilian dyslipidaemic children and adolescents. A total of fifty
      one individuals (6-19 years) with mild-to-moderate hypercholesterolaemia were
      evaluated by conducting a randomised, double-blind, placebo-controlled, parallel
      clinical trial. Over an 8-week trial period, the participants were randomly
      allocated to one of two groups (control: n 25 and psyllium: n 26) using a
      computer-generated random number sequence. Fasting blood samples, dietary records
      and anthropometric data were collected. Both groups were treated with the
      National Cholesterol Education Program Step 2 diet for 6 weeks before
      randomisation. After this run-in period, a daily supplement of 7.0 g psyllium was
      given to the intervention group, while an equivalent amount of cellulose was
      given to the control group. Statistically significant changes between the control
      and intervention groups over time were observed for total cholesterol (7.7%; -
      0.39 mmol/l; P= 0.003) and LDL-C (10.7%; - 0.36 mmol/l; P= 0.01). None of the
      participants reported any aversion to the smell, taste, appearance or texture of
      psyllium. No serious adverse effects were reported during the study. In addition
      to causing a significant reduction in LDL-C concentrations, psyllium therapy was
      found to be both safe and acceptable for the treatment of hypercholesterolaemic
      children and adolescents.

PMID- 25391815
TI  - Betwixt and between: workplace perspectives on work reintegration in the
      eldercare sector in Denmark.
AB  - PURPOSE: Contemporary return-to-work (RTW) policies in Denmark and other welfare
      nations recommend employees on long-term sick leave, due to physical or mental
      health problems, to RTW gradually. Factors that influence the process of work
      reintegration (WR) is well documented, however, co-workers experiences of this
      process are a rather new research topic. Moreover, in the context of the present
      research, no studies have so far explored the workplace as an arena for social
      interaction. The aim of this study was to explore co-workers' experiences of the
      reintegration process and how these experiences are related to social positions
      at the workplace. METHODS: Ethnographic fieldwork was conducted at two nursing
      homes that were in a process WR after long-term sick leave. The data consist of
      field notes, policy documents, individual interviews, and focus group interviews.
      Data were organized by use of NVivo. A theoretical framework was adopted which
      enabled us to approach and interpret the reintegration process as one that
      changed the social position of the returning employee. RESULTS: The dataset
      demonstrates how the returnee is in a state of being betwixt and between the
      social positions of a co-worker and a non-co-worker. This is illustrated in three
      cases which show that this state prevents the returnee from taking on the role as
      a co-worker, excludes the returnee from the workplace, and creates uncertainty
      for all workplace actors. CONCLUSION: The study highlighted that WR creates a
      social position for the returnee that complicates the working routine and causes
      uncertainty in social interactions. Implications for Rehabilitation Work
      reintegration (WR) after long-term sick leave is commonly characterized by
      reduced working hours and modified working tasks. The WR process influences the
      whole work place including co-workers' everyday working life and complicates work
      situations where work tasks and roles are negotiated between the returning worker
      and co-workers. Future WR policies and guidelines could benefit from integrating
      co-workers' perspective to ensure that the returning worker is not socially
      excluded as well as ensuring that co-workers are not overburdened in the process.

PMID- 25391816
TI  - Severe to profound hearing impairment: quality of life, psychosocial consequences
      and audiological rehabilitation.
AB  - PURPOSE: To study the quality of life (QoL) and psychosocial consequences in
      terms of sick leave and audiological rehabilitation given to patients with severe
      to profound hearing impairment. METHOD: A retrospective study of data on 2319
      patients with severe to profound hearing impairment in The Swedish Quality
      Register of Otorhinolaryngology, followed by a posted questionnaire including The
      Hospital Anxiety and Depression Scale (HADS). RESULTS: The results indicate
      greater levels of anxiety and depression among patients with severe or profound
      hearing impairment than in the general population, and annoying tinnitus and
      vertigo had strong negative effects on QoL. The proportion of sick leave differed
      between the studied dimensions in the study. The proportion of patients who
      received extended audiological rehabilitation was 38% in the present study.
      CONCLUSIONS: Treatment focused on anxiety, depression, tinnitus and vertigo must
      be given early in the rehabilitation process in patients with severe or profound
      hearing impairment. Because sick leave differs greatly within this group of
      patients, collaboration with the regional Social Insurance Agency is crucial part
      of the rehabilitation. The study also shows that presently, only a small
      proportion of patients in Sweden with severe to profound hearing impairment
      receive extended audiological rehabilitation. Implications for Rehabilitation
      Greater levels of anxiety and depression have been found among patients with
      severe or profound hearing impairment than in the general population, and
      annoying tinnitus and vertigo have strong negative effects on QoL in this group
      of patients. Only a small proportion of patients with severe to profound hearing
      impairment receive extended audiological rehabilitation today, including medical,
      technical and psychosocial efforts. Extended audiological rehabilitation focused
      on anxiety, depression, tinnitus and vertigo must be given, together with
      technical rehabilitation, early in the rehabilitation process in patients with
      severe or profound hearing impairment.

PMID- 25391817
TI  - Community re-integration and long-term need in the first five years after stroke:
      results from a national survey.
AB  - PURPOSE: Acute stroke care continues to improve but the later stroke recovery
      phase remains less well understood. The aim of this study was to document self
      reported need in relation to stroke recovery and community re-integration among
      community-dwelling persons up to five years post-stroke. METHODS: A national
      survey was carried out in Ireland. Participants were recruited through stroke
      advocacy organisations and health professionals. Existing validated
      questionnaires were adapted with permission. The final questionnaire assessed
      respondents' perceptions of their community re-integration and on-going needs.
      RESULTS: A total of 196 stroke survivors, aged 24-89 years responded. Over 75% of
      respondents reported experiencing mobility, emotional, fatigue and concentration
      difficulties post-stroke. Emotional problems and fatigue demonstrated the highest
      levels of unmet need. Families provided much support with 52% of people needing
      help with personal care post-stroke. Forty-two per cent of respondents in a
      relationship felt that it was significantly affected by their stroke. In
      addition, 60% of respondents reported negative financial change. Only 23% of
      those <66 years had worked since their stroke, while 60% of drivers returned to
      driving. CONCLUSIONS: Stroke had a personal, social and economic impact.
      Emotional distress and fatigue were common and satisfaction with the help
      available for these problems was poor. Implications for Rehabilitation
      Professionals should recognise that family members provide high levels of support
      post-stroke while dealing with changes to personal relationships. Emotional,
      concentration and fatigue problems post-stroke require recognition by health
      professionals. A greater focus on return-to-work as part of stroke rehabilitation
      may be of value for patients of working age.

PMID- 25391818
TI  - Activation of AMP-activated protein kinase by metformin protects human coronary
      artery endothelial cells against diabetic lipoapoptosis.
AB  - BACKGROUND: The prevalence of type 2 diabetes (T2D) among adults worldwide is
      rapidly increasing, and in patients with diabetes the major cause of death is
      macrovascular disease. Endothelial cells play an important role in maintaining
      vascular homeostasis. Free fatty acids, which are elevated in T2D, have
      previously been shown to induce endothelial dysfunction and apoptosis of
      endothelial cells, which is considered as an important and early factor in the
      onset of atherosclerosis and cardiovascular disease. Metformin, which is used as
      first line treatment of T2D patients, is believed to exert its pharmacological
      effects through activation of AMP-activated protein kinase, which has emerged as
      a new potential target in reversing endothelial dysfunction. METHODS: Here we
      studied the protective effect of metformin against free fatty acid-induced
      apoptosis of human coronary artery endothelial cells (HCAECs) by assessing DNA
      fragmentation and cleaved caspase 3 levels. We also attempted to elucidate the
      underlying mechanisms by investigating the involvement of AMP-activated protein
      kinase, p38 MAPK and eNOS. Generation of reactive oxygen species by free fatty
      acid exposure was also examined. RESULTS: Our results suggest that metformin
      protects HCAECs from lipoapoptosis, an effect that involves eNOS and p38 MAPK,
      downstream of AMPK signaling, but not as previously suggested through suppression
      of reactive oxygen species. CONCLUSION: The protective effect of metformin
      against free fatty acid induced apoptosis is potentially clinically relevant as
      metformin is first line treatment for patients with T2D, a patient group which is
      rapidly increasing and carries a high burden of cardiovascular disease.

PMID- 25391819
TI  - Dihydroxanthenones from the fermentation product of an endophytic fungus
      Gliomastix murorum.
AB  - Three new dihydroxanthones, muroxanthenones A-C (1-3), together with three known
      dihydroxanthones (4-6) were isolated from the fermentation products of an
      endophytic fungus Gliomastix murorum. Their structures were elucidated by
      spectroscopic methods, including extensive 1D and 2D NMR techniques. Compound 3
      showed high cytotoxicities against NB4 and PC3 cell with IC(50) values of 2.2 and
      2.8 MUM. The other compounds also showed moderate cytotoxicities for some tested
      cell lines with IC(50) values between 4.1 and 9.5 MUM.

PMID- 25391820
TI  - Mechanical thrombectomy for acute stroke in childhood: how much does restricted
      diffusion matter?
AB  - Mechanical thrombectomy holds promise for children with large cerebral arterial
      occlusions, although there are few reports in this population. We report a case
      of retrievable stent-assisted mechanical thrombectomy in a 5-year-old with
      basilar artery occlusion, despite late presentation and extensive initial
      diffusion-weighted imaging (DWI) restriction. This resulted in successful
      Thrombolysis in Cerebral Infarction 2B reperfusion and excellent clinical
      outcome. At 6-week follow-up he was completely back to baseline with no residual
      deficits (pediatric stroke outcome measure=0, modified Rankin scale=0). At 3
      month follow-up the patient has not had any recurrent stroke or concern for
      stroke-like symptoms. We review the literature on mechanical thrombectomy and DWI
      changes in acute stroke in early to middle childhood (<12 years old).

PMID- 25391821
TI  - Diagnosing scrub typhus: meticulous physical examination is the key.

PMID- 25391822
TI  - Recurrent gallstone ileus: beware of the faceted stone.
AB  - A 73-year-old man with gallstone disease was admitted with right upper quadrant
      abdominal pain. He was treated for cholecystitis with intravenous antibiotics.
      Two days later, he reported of new onset left iliac fossa pain, with tenderness
      and guarding. An abdominal X-ray demonstrated small bowel obstruction, a CT scan
      demonstrated an impacted gallstone within the proximal ileum. He was treated for
      a gallstone ileum and underwent an uncomplicated laparotomy, small bowel
      enterotomy and removal of a faceted gallstone. Three months later, the patient re
      presented with generalised abdominal pain, guarding and rebound tenderness. Small
      bowel obstruction was again demonstrated with an impacted gallstone within the
      distal ileum seen on CT scan. A second laparotomy revealed two further faceted
      gallstones, which were removed through an enterotomy. The densely adherent
      gallbladder to the duodenum precluded a surgical repair of the cholecystoduodenal
      fistula. He made an uneventful recovery and was subsequently discharged home. 

PMID- 25391823
TI  - Adrenocortical carcinoma mimicking lung cancer and responding to
      vinorelbine/carboplatin and pemetrexed/carboplatin.
AB  - Adrenocortical carcinoma is an aggressive cancer, with an incidence of 0.5-2 per
      million. We present a case of adrenocortical carcinoma with all the clinical and
      partly immunohistochemical features of disseminated undifferentiated lung cancer,
      and 'accidentally' treated as such. Four cycles of carboplatin-vinorelbine
      conferred partial response in the adrenal, lung and disappearance of a 2 cm
      subcutaneous iliac nodule that had appeared suddenly before the first course.
      Owing to progression, four cycles of carboplatin-pemetrexed were administered
      inducing partial response and then stable disease for an additional 12 months. As
      fluoro-d-glucose (FDG)-positron emission tomography (PET) only showed activity in
      the adrenal, laparoscopic adrenalectomy was performed. Three months later FDG-PET
      revealed a lung nodule unresponsive to carboplatin-pemetrexed, removed by wedge
      resection. Finally, re-evaluation by a tertiary centre confirmed adrenocortical
      carcinoma with Ki67-50% in the adrenal and the lung. The patient is alive and
      tumour free almost 3.5 years after retrospective diagnosis of metastatic
      adrenocortical cancer.

PMID- 25391824
TI  - 'Little old lady's hernia' causing small bowel obstruction in a man: a case
      report with a review of literature on the pathophysiology of obturator hernias.
AB  - Commonly known as 'little old lady's hernia', obturator hernias are usually seen
      in frail, octogenarian multiparous women reporting non-specific nausea and
      vomiting, abdominal pain and anteromedial thigh pain. They are exceedingly rare;
      even less frequently are they diagnosed preoperatively, with the vast majority
      being found incidentally at laparotomy for small bowel obstruction. This case
      report describes an atypical presentation of a 'little old lady's hernia' in a
      man, in whom, thanks to high degree of clinical suspicion, an incarcerated
      obturator hernia was diagnosed preoperatively and treated successfully. 

PMID- 25391825
TI  - Citalopram-induced hyponatraemia and parkinsonism: potentially fatal side-effects
      not to be missed.
AB  - The use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram,
      is on the rise and, as such, clinicians must be vigilant of rare side-effects
      associated with this group of medications. We report the case of a 65-year-old
      man who presented to West Suffolk Hospital with a fall, confusion and movement
      abnormalities, and was found to have a serum sodium of 105 on admission. He was
      managed with hypertonic saline, dopamine agonists and intensive physiotherapy.
      Despite initially deteriorating neurologically, he made a remarkable recovery,
      and was discharged home at his pre-admission baseline. The learning points from
      this report are as follows: (1) regular monitoring of electrolytes on starting an
      SSRI (and similarly selective noradrenaline reuptake inhibitors-SNRIs) in
      SSRI/SNRIs naive patients, (2) awareness of possible citalopram-induced
      parkinsonism and the potential benefits of dopamine agonists as one management
      strategy and (3) vigilant fluid/electrolyte monitoring in patients with profound
      hyponatraemia. 

PMID- 25391826
TI  - A demonstration of peristomal ulceration in the setting of nicorandil therapy.

PMID- 25391827
TI  - Myocardial infarction following cannabis induced coronary vasospasm.
AB  - Smoking cannabis is a rare cause of myocardial infarction. We report a 29-year
      old man who presented with acute coronary syndrome following consumption of a
      type of cannabis with the street name 'Kerala Ganja'. KG is smuggled into Sri
      Lanka from India; it is grown in the south Indian state of Kerala and is much
      more potent than the local ganja (marijuana). The patient developed dynamic ST
      segment elevations in different leads in sequential ECGs, corresponding to
      different coronary artery territories. Coronary angiogram did not demonstrate
      evidence of occlusive atherosclerotic disease, but showed slow flow down the left
      anterior descending artery, which improved with administration of intracoronary
      nitrates. The patient's cardiac biomarkers were significantly elevated. A
      diagnosis was made of vasospasm causing myocardial infarction, most likely to
      have been triggered by cannabis consumption. We highlight the importance of
      considering this possible aetiology, particularly in patients with ACS with a
      susceptible social profile. 

PMID- 25391828
TI  - Sudden death in a patient with bone marrow transplant by a fungus among us.
AB  - Mucormycosis is rare, presenting as breakthrough infection among haematological
      and transplant patients on prophylaxis with voriconazole. We report an unusual
      presentation of this infection, that which is pneumonia progressing to cardiac
      arrest. A 68-year-old woman with refractory acute myelogenous leukaemia on
      voriconazole prophylaxis was initially admitted for neutropenic fever and
      pneumonia. She was discharged improved on antibiotics and voriconazole for
      presumed aspergillosis. She returned after 1 month with the same presentation.
      She eventually improved on antibiotics and voriconazole, and eventually received
      bone marrow transplantation. Three days later, she developed pleuritic chest
      pain, dyspnoea, and hypoxia requiring intubation. An hour after intubation, the
      patient arrested and expired. Autopsy revealed Rhizopus pneumonitis with
      pulmonary infarction, and emboli to her cerebellum, heart, thyroid and kidney.
      Mucormycosis is an emerging, fatal infection that should be suspected in
      haematological and transplant patients who deteriorate on voriconazole.

PMID- 25391829
TI  - A fourth case of Feingold syndrome type 2: psychiatric presentation and
      management.
AB  - Feingold syndrome (FGLDS1) is an autosomal dominant disorder caused by mutations
      in the MYCN oncogene on the short arm of chromosome 2 (2p24.1). It is
      characterised by microcephaly, digital abnormalities, oesophageal and duodenal
      atresias, and often learning disability or mental retardation. In 2011,
      individuals sharing the skeletal abnormalities of FGLDS1 but lacking mutations in
      MYCN, were found to harbour hemizygous deletions of the MIR17HG gene on
      chromosome 13q31.3. These individuals share many of the characteristics of FGLDS1
      except for gastrointestinal atresia. The condition was termed Feingold syndrome
      type 2 (FGLDS2). We describe the presentation and management of a fourth known
      case of FGLDS2 in an 18-year-old girl with microcephaly, short stature, mildly
      dysmorphic features, digital malformations and significant cognitive and
      psychiatric symptoms. Comparative genomic hybridisation array testing confirmed a
      7.4 Mb microdeletion in chromosome region 13q31.1q.31.3 corresponding to the
      MIR17HG gene. 

PMID- 25391830
TI  - Transillumination: shining a light from within.

PMID- 25391831
TI  - Surveillance of work-related amputations in Michigan using multiple data sources:
      results for 2006-2012.
AB  - OBJECTIVES: An amputation is one of the most serious injuries an employee can
      sustain and may result in lost time from work and permanent limitations that
      restrict future activity. A multidata source system has been shown to identify
      twice as many acute traumatic fatalities as one relying only on employer
      reporting. This study demonstrates the value of a multidata source approach for
      non-fatal occupational injuries. METHODS: Data were abstracted from medical
      records of patients treated for work-related amputations at Michigan hospitals
      and emergency departments and were linked to workers' compensation claims data.
      Safety inspections were conducted by the Michigan Occupational Safety and Health
      Administration for selected cases. RESULTS: From 2006 through 2012, 4140 Michigan
      residents had a work-related amputation. In contrast, the Survey of Occupational
      Injury and Illness conducted by the Bureau of Labor Statistics (BLS) estimated
      that there were 1770 cases during this period. During the 7-year period, work
      related amputation rates decreased by 26%. The work-related amputation rate for
      men was more than six times that for women. Industries with the highest work
      related amputation rates were Wood Product Manufacturing and Paper Manufacturing.
      Power saws and presses were the leading causes of injury. One hundred and seventy
      three safety inspections were conducted as a result of referrals from the system.
      These inspections identified 1566 violations and assessed $652 755 in penalties.
      CONCLUSIONS: The system was fairly simple to maintain, identified more than twice
      as many cases than either BLS or workers' compensation alone, and was useful for
      initiating inspection of high-risk worksites.

PMID- 25391832
TI  - Early prognosis of noise-induced hearing loss: prioritising prevention over
      prediction.

PMID- 25391833
TI  - Associations between rushed condom application and condom use errors and
      problems.
AB  - OBJECTIVE: To determine whether any of four condom use errors/problems occurred
      more frequently when condom application was 'rushed' among a clinic-based sample
      from three US states. METHODS: A convenience sample (n=512) completed daily
      electronic assessments including questions about condom use being rushed and also
      assessed condom breakage, slippage, leakage and incomplete use. RESULTS: Of 8856
      events, 6.5% (n=574) occurred when application was rushed. When events involved
      rushed condom application, the estimated odds of breakage and slippage were
      almost doubled (estimated OR (EOR)=1.90 and EOR=1.86). Rushed application
      increased the odds of not using condoms throughout sex (EOR=1.33) and nearly
      tripled the odds of leakage (EOR=2.96). With one exception, all tests for
      interactions between gender and rushed application and between age and rushed
      application were not significant (p values>0.10). CONCLUSIONS: This event-level
      analysis suggests that women and men who perceive that condom application was
      rushed are more likely to experience errors/problems during the sexual event that
      substantially compromise the protective value of condoms against disease and
      pregnancy. Educational efforts emphasising the need to allow ample time for
      condom application may benefit this population.

PMID- 25391834
TI  - [Acute respiratory and renal failure in a 20-year-old man].

PMID- 25391836
TI  - Bone marrow Th17 TNFalpha cells induce osteoclast differentiation and link bone
      destruction to IBD.

PMID- 25391835
TI  - HdeB functions as an acid-protective chaperone in bacteria.
AB  - Enteric bacteria such as Escherichia coli utilize various acid response systems
      to counteract the acidic environment of the mammalian stomach. To protect their
      periplasmic proteome against rapid acid-mediated damage, bacteria contain the
      acid-activated periplasmic chaperones HdeA and HdeB. Activation of HdeA at pH 2
      was shown to correlate with its acid-induced dissociation into partially unfolded
      monomers. In contrast, HdeB, which has high structural similarities to HdeA,
      shows negligible chaperone activity at pH 2 and only modest chaperone activity at
      pH 3. These results raised intriguing questions concerning the physiological role
      of HdeB in bacteria, its activation mechanism, and the structural requirements
      for its function as a molecular chaperone. In this study, we conducted structural
      and biochemical studies that revealed that HdeB indeed works as an effective
      molecular chaperone. However, in contrast to HdeA, whose chaperone function is
      optimal at pH 2, the chaperone function of HdeB is optimal at pH 4, at which HdeB
      is still fully dimeric and largely folded. NMR, analytical ultracentrifugation,
      and fluorescence studies suggest that the highly dynamic nature of HdeB at pH 4
      alleviates the need for monomerization and partial unfolding. Once activated,
      HdeB binds various unfolding client proteins, prevents their aggregation, and
      supports their refolding upon subsequent neutralization. Overexpression of HdeA
      promotes bacterial survival at pH 2 and 3, whereas overexpression of HdeB
      positively affects bacterial growth at pH 4. These studies demonstrate how two
      structurally homologous proteins with seemingly identical in vivo functions have
      evolved to provide bacteria with the means for surviving a range of acidic
      protein-unfolding conditions. 

PMID- 25391837
TI  - Meniere's disease.

PMID- 25391838
TI  - Mike Smith: In a tug of war for patient centred care.

PMID- 25391839
TI  - Clap along if you feel like happiness is linked to money.

PMID- 25391840
TI  - Scotland flaunts its looks to attract GPs.

PMID- 25391841
TI  - Time to think Ebola: a message from NHS England to frontline clinical staff.

PMID- 25391842
TI  - NHS leaders remind frontline staff to be alert to Ebola infection.

PMID- 25391843
TI  - Basics of DNA biosensors and cancer diagnosis.
AB  - The human genome is exposed to mutations during the life cycle because of many
      types of changes in the DNA. Viruses, radiation, transposons, mutagenic
      chemicals, or any errors that happen during DNA replication or the meiotic
      process in the cell, may cause the mutation. Many mutations have no effect on
      phenotype or health, while some mutations cause crucial diseases such as cancer
      or cardiac diseases; therefore, a better understanding of the effects of mutation
      on phenotype is a very important part of genetic studies. Biosensors based on
      DNA, RNA, and peptide nucleic acids are the most sensitive tools, due to a strong
      pairing of lined up nucleotide strands between bases in their complementary
      parts. These methods can provide information to assist clinicians in making
      successful treatment decisions and increase the patient survival rate. In this
      review, we discuss DNA biosensors based on peptide nucleic acids that have an
      important role in cancer diagnosis. 

PMID- 25391844
TI  - A cost management model for hospital food and nutrition in a public hospital.
AB  - BACKGROUND: In Chile, the use of costing systems in the public sector is limited.
      The Ministry of Health requires hospitals to manage themselves with the aim of
      decentralizing health care services and increasing their quality. However, self
      management with a lack of accounting information is almost impossible. On the
      other hand, nutrition department costs have barely been studied before, and there
      are no studies specifically for activity based costing (ABC) systems. ABC focuses
      on the process and traces health care activities to gain a more accurate
      measurement of the object costs and the financial performance of an organization.
      METHOD: This paper uses ABC in a nutrition unit of a public hospital of high
      complexity to determine costs associated with the different meals for inpatients.
      The paper also provides an activity based management (ABM) analysis for this
      unit. RESULTS: The results show positive effects on the reduction of costs for
      the nutrition department after implementing ABC/ABM. Therefore, there are
      opportunities to improve the profitability of the area and the results could also
      be replicated to other areas in the hospital. ABC shed light on the amount of
      nutritionist time devoted to completing paperwork, and as a result, system
      changes were introduced to reduce this burden and allow them to focus on more
      relevant activities. Additional efficiencies were achieved through the
      elimination of non-value adding activities and automation of reports. ABC reduced
      the cost of the nutrition department and could produce similar results in other
      areas of the hospital. CONCLUSIONS: This is a practical application of a
      financial management tool, ABC, which would be useful for hospital managers to
      reduce costs and improve the management of the unit. This paper takes ABC and
      examines its use in an area, which has had little exposure to the benefits of
      this tool.

PMID- 25391846
TI  - A mitochondrial intron in a verongid sponge.
AB  - We discovered for the first time a mitochondrial intron in a non-tetillid
      demosponge, which sheds new light on the interpretation of mitochondrial intron
      evolution among non-bilaterian animals and has consequences for phylogenetic and
      DNA barcoding studies. The newly discovered class 1 intron of Aplysinella rhax
      (Verongida) CO1 has an ORF for a putative LAGLIDADG-type and resembles other
      sponge and cnidarian mitochondrial introns. Our analysis of the Aplysinella rhax
      intron underlines that the patchy distribution of introns in sponges is caused by
      a combination of horizontal and vertical transmission. Further implications for
      CO1 phylogenetic and barcoding projects are discussed. 

PMID- 25391847
TI  - Does use of computer technology for perinatal data collection influence data
      quality?
AB  - Population health data, collected worldwide in an effort to monitor mortality and
      morbidity of mothers and babies, namely, perinatal data, are mandated at a
      federal level within Australia. The data are used to monitor patterns in
      midwifery, obstetric and neonatal practice, health outcomes, used for research
      purposes, funding allocation and education. Accuracy in perinatal data is most
      often reported via quantitative validation studies of perinatal data collections
      both internationally and in Australia. These studies report varying levels of
      accuracy and suggest researchers need to be more aware of the quality of data
      they use. This article presents findings regarding issues of concern identified
      by midwives relating to their perceptions of how technology affects the accuracy
      of perinatal data records. Perinatal data records are perceived to be more
      complete when completed electronically. However, issues regarding system
      functionality, the inconsistent use of terminology, lack of data standards and
      the absence of clear, written records contribute to midwives' perceptions of the
      negative influence of technology on the quality of perinatal data.

PMID- 25391848
TI  - Statistical classification of drug incidents due to look-alike sound-alike mix
      ups.
AB  - It has been recognised that medication names that look or sound similar are a
      cause of medication errors. This study builds statistical classifiers for
      identifying medication incidents due to look-alike sound-alike mix-ups. A total
      of 227 patient safety incident advisories related to medication were obtained
      from the Canadian Patient Safety Institute's Global Patient Safety Alerts system.
      Eight feature selection strategies based on frequent terms, frequent drug terms
      and constituent terms were performed. Statistical text classifiers based on
      logistic regression, support vector machines with linear, polynomial, radial
      basis and sigmoid kernels and decision tree were trained and tested. The models
      developed achieved an average accuracy of above 0.8 across all the model
      settings. The receiver operating characteristic curves indicated the classifiers
      performed reasonably well. The results obtained in this study suggest that
      statistical text classification can be a feasible method for identifying
      medication incidents due to look-alike sound-alike mix-ups based on a database of
      advisories from Global Patient Safety Alerts.

PMID- 25391845
TI  - Oocyte ageing and epigenetics.
AB  - It has become a current social trend for women to delay childbearing. However,
      the quality of oocytes from older females is compromised and the pregnancy rate
      of older women is lower. With the increased rate of delayed childbearing, it is
      becoming more and more crucial to understand the mechanisms underlying the
      compromised quality of oocytes from older women, including mitochondrial
      dysfunctions, aneuploidy and epigenetic changes. Establishing proper epigenetic
      modifications during oogenesis and early embryo development is an important
      aspect in reproduction. The reprogramming process may be influenced by external
      and internal factors that result in improper epigenetic changes in germ cells.
      Furthermore, germ cell epigenetic changes might be inherited by the next
      generations. In this review, we briefly summarise the effects of ageing on oocyte
      quality. We focus on discussing the relationship between ageing and epigenetic
      modifications, highlighting the epigenetic changes in oocytes from advanced-age
      females and in post-ovulatory aged oocytes as well as the possible underlying
      mechanisms. 

PMID- 25391849
TI  - A feasibility study of conducting the Montreal Cognitive Assessment remotely in
      individuals with movement disorders.
AB  - Remote assessments of individuals with a neurological disease via telemedicine
      have the potential to reduce some of the burdens associated with clinical care
      and research participation. We aim to evaluate the feasibility of conducting the
      Montreal Cognitive Assessment remotely in individuals with movement disorders. A
      pilot study derived from two telemedicine trials was conducted. In total, 17
      individuals with movement disorders (8 with Parkinson disease and 9 with
      Huntington disease) had Montreal Cognitive Assessment examinations evaluated in
      person and remotely via web-based video conferencing to primarily determine
      feasibility and potential barriers in its remote administration. Administering
      the Montreal Cognitive Assessment remotely in a sample of movement disorder
      patients with mild cognitive impairment is feasible, with only minor common
      complications associated with technology, including delayed sound and corrupted
      imaging for participants with low connection speeds. The Montreal Cognitive
      Assessment has the potential to be used in remote assessments of patients and
      research participants with movement disorders.

PMID- 25391850
TI  - The web-buffet--development and validation of an online tool to measure food
      choice.
AB  - OBJECTIVE: To date, no data exist on the agreement of food choice measured using
      an online tool with subsequent actual consumption. This needs to be shown before
      food choice, measured by means of an online tool, is used as a dependent variable
      to examine intake in the general population. DESIGN: A 'web-buffet' was developed
      to assess food choice. SETTING: Choice was measured as planned meal composition
      from photographic material; respondents chose preferred foods and proportions for
      a main meal (out of a possible 144 combinations) online and the validity was
      assessed by comparison of a meal composed from a web-buffet with actual food
      intake 24-48 h later. Furthermore, correlations of food preferences, energy needs
      and health interest with meals chosen from the web-buffet were analysed.
      SUBJECTS: Students: n 106 (Study I), n 32 (Study II). RESULTS: Meals chosen from
      the web-buffet (mean = 2998 kJ, SD = 471 kJ) agreed with actual consumption (rs =
      0.63, P < 0.001) but were on average 367 kJ (10.5%) lower in energy than consumed
      meals (mean = 3480 kJ, SD = 755 kJ). Preferences were highly associated with
      chosen amounts and health interest was negatively correlated with the energy
      selected (rs = -0.40, P<0.001). CONCLUSIONS: Meal composition choice in the web
      buffet agrees sufficiently well with actual intake to measure food choice as a
      dependent variable in online surveys. However, we found an average
      underestimation of subsequent consumption. High correlations of preferences with
      chosen amounts and an inverse association of health interest with total energy
      further indicate the validity of the tool. Applications in behavioural nutrition
      research are discussed.

PMID- 25391851
TI  - The life cycle of the heart failure patient.

PMID- 25391853
TI  - Interrupting the dark dance of bribery.

PMID- 25391852
TI  - Device therapies: new indications and future directions.
AB  - Implantable cardioverter-defibrillator (ICDs), cardiac resynchronization (CRT)
      and combination (CRT-D) therapy have become an integral part of the management of
      patients with heart failure with reduced ejection fraction (HFrEF). ICDs treat
      ventricular arrhythmia and CRTs improve left ventricular systolic function by
      resynchronizing ventricular contraction. Device therapies (ICD, CRT-D), have been
      shown to reduce all-cause mortality, including sudden cardiac death.
      Hospitalizations are reduced with CRT and CRT-D therapy. Major device related
      complications include device infection, inappropriate shocks, lead malfunction
      and complications related to extraction of devices. Improvements in device design
      and implantation have included progressive miniaturization and increasing battery
      life of the device, optimization of response to CRT, and minimizing inappropriate
      device therapy. Additionally, better definition of the population with the
      greatest benefit is an area of active research. 

PMID- 25391855
TI  - Leiomyoma--a rare benign tumor of the female urethra: a case report.
AB  - INTRODUCTION: Leiomyoma in the urethra is a rare occurrence. These are rare
      benign mesenchymal tumors that arise from the smooth muscle of the urethra. Such
      tumors often appear in females during their reproductive age (from menarche to
      menopause); the mean age of their appearance is approximately 41 years. CASE
      PRESENTATION: We report here a case of a 52-year-old White woman who presented
      with complaints of sporadic hematuria, dyspareunia, and feeling of nodulation in
      her vagina. CONCLUSIONS: Histopathological studies confirmed the urethral
      leiomyoma, and the surgery completely resolved the original symptoms. Although
      the average age of occurrence of such tumors in females is about 41 years, the
      present case involves an older woman of 52 years. Most importantly, the mass was
      located in the distal urethra, an uncommon site of presentation of leiomyoma in
      females.

PMID- 25391854
TI  - Decreased EAAT2 protein expression in the essential tremor cerebellar cortex.
AB  - Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate
      transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2
      encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate
      from the synaptic cleft. One postulated mechanism for essential tremor is the
      over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to
      excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are
      transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons.
      Therefore, the expression level of glutamate transporters could be important in
      essential tremor pathogenesis. Using Western blotting, we compared the expression
      levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and
      EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched
      controls. We also studied the localization of EAAT1 and EAAT2 using
      immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein
      levels were similar in cases and controls (1.12 +/- 0.83 vs. 1.01 +/- 0.69, p
      =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of
      that in controls (0.35 +/- 0.23 vs. 1.00 +/- 0.62, p < 0.01). Interestingly,
      EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the
      Purkinje cell axon initial segment, a region of previously observed pathological
      changes in essential tremor. Our main finding, a significant reduction in
      cerebellar cortical EAAT2 protein levels in essential tremor, suggests that
      Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage
      than those of controls. 

PMID- 25391856
TI  - Unstable hip arthroplasties. A prospective cohort study on seventy dislocating
      hips followed up for four years.
AB  - PURPOSE: Dislocating hip prosthesis remains a substantial clinical problem. The
      aim of this study is to describe the risk of recurrent instability after a
      primary dislocation of primary hip arthroplasty performed for osteoarthritis (OA)
      or femoral neck fracture (FNF). METHODS: Seventy patients (male/females: 25/45;
      mean age 77 [range 46-94]) with dislocating hip arthroplasties were included in a
      prospective cohort study and followed for four years. Radiographs and all
      surgical records were reviewed. We compared stable hips to those who either
      continued to dislocate or were revised due to recurrent instability (unstable
      group). RESULTS: Forty-two hips (60 %) had episodes of recurrent instability
      leading to repeated closed reductions or major revision surgery and were
      classified as unstable. A diagnosis of FNF and cognitive dysfunction (OR 9.3 [95
      % CI 1.4-64.1]) or postoperative radiological discrepancies such as leg
      lengthening and offset reduction increased the risk of further instability (OR
      13.5 [95 % CI 1.3-148.1]). The surgical approach at primary surgery and ASA class
      did not significantly influence the risk of continued instability. CONCLUSIONS:
      Patients with a FNF and cognitive dysfunction or with sub-optimal postoperative
      radiographs after hip arthroplasty surgery are at high risk of recurrent
      instability after a primary dislocation. For hip fracture patients, all efforts
      should be made to avoid the first dislocation.

PMID- 25391857
TI  - Oleic acid stimulates glucose uptake into adipocytes by enhancing insulin
      receptor signaling.
AB  - The present study investigated cis-unsaturated free fatty acid (FFA)-regulated
      glucose uptake. In the cell-free assay of protein tyrosine phosphatase 1B
      (PTP1B), cis-unsaturated FFAs such as linoleic, linolenic, and oleic acid
      significantly suppressed PTP1B activity in a concentration (1 - 100 MUM)
      dependent manner, with the highest potential for oleic acid. Oleic acid (1 MUM)
      stimulated insulin (0.1 nM)-induced phosphorylation of the insulin receptor at
      Tyr1185 and increased insulin (0.1 nM)-induced phosphorylation of Akt at Thr308
      and Ser473 in differentiated 3T3-L1-GLUT4myc adipocytes. In the foerster
      resonance energy transfer analysis, oleic acid activated Rac1 in PC-12 cells,
      which is inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor
      wortmannin, the 3-phosphoinositide-dependent protein kinase-1 (PDK1) inhibitor
      BX912, or the Akt inhibitor MK2206. Oleic acid (1 MUM) significantly increased
      insulin (0.1 nM)-stimulated glucose uptake in 3T3-L1-GLUT4myc adipocytes,
      although oleic acid by itself had no effect on the glucose uptake. Taken
      together, the results of the present study show that oleic acid enhances insulin
      receptor signaling through a pathway along an insulin receptor/PI3K/PDK1/Akt/Rac1
      axis in association with PTP1B inhibition and facilitates insulin-induced glucose
      uptake into adipocytes.

PMID- 25391859
TI  - [Clinical application of low radiation and low-contrast dose in CT].

PMID- 25391860
TI  - [Perspective of "dual low" technique in cardiovascular diseases].

PMID- 25391858
TI  - Balancing benefits and risks in patients receiving incretin-based therapies:
      focus on cardiovascular and pancreatic side effects.
AB  - Incretin-based therapies either increase endogenous levels of glucagon-like
      peptide-1 by prolonging its half-life (DPP-4 inhibitors) or directly stimulate
      its receptor (glucagon-like peptide-1 analogues; GLP-1 RA). They are currently
      widely used for the treatment of patients with type 2 diabetes mellitus owing to
      good antidiabetic efficacy, low risk of hypoglycemia, and relatively few other
      side effects. They also offer potential additional benefits such as weight
      neutrality or weight loss, positive effects on blood pressure and lipid levels,
      and potential cardio- and neuroprotectivity. Some experimental and clinical
      studies have raised concerns with respect to potential cardiovascular and
      pancreatic side effects of these therapies such as increased risk of heart
      failure with DPP-4 inhibitors as well as acute pancreatitis and pancreatic cancer
      with both classes. The available data are at present not robust enough to enable
      firm conclusions regarding these potential associations. Nevertheless, some
      recent data suggest a possibility of slightly increased risk of acute
      pancreatitis with GLP-1 RAs while they do not indicate increased risk of
      pancreatic cancer. Ongoing cardiovascular outcome trials will shed more light on
      the possible cardioprotective effects of incretin-based therapies as well as on
      the possible interconnection of DPP-4 inhibitors and heart failure. 

PMID- 25391861
TI  - [Better understanding of "dual low" concept and its application in CTA of head
      and neck].

PMID- 25391862
TI  - [Perspective of "dual low" technique in neural system].

PMID- 25391863
TI  - [Development of abdominal CT "dual low" technique].

PMID- 25391864
TI  - [Study of low radiation exposure dose and low contrast medium dose in coronary CT
      angiography with High-pitch spiral acquisition mode of dual source CT].
AB  - OBJECTIVE: To evaluate the feasibility of low radiation exposure and low contrast
      medium volume for coronary CT angiography with High- pitch spiral acquisition
      mode of dual source CT. METHODS: 135 patients whose BMI <23 kg/m2 and heart rates
      <65 bpm selected from 291 patients diagnosed of suspected CHD at our institution
      from September 2013 to February 2014 were randomly divided into 3 groups before
      CCTA, and there were 45 patients in each group. 80 kV , Iodixanol (320 mgI/ml)
      and sinogram affirmed iterative reconstruction (SAFIRE) were used in A group. 80
      kV , Iopamidol (370 mgI/ml) and SAFIRE were used in B group. 100 kV, Iodixanol
      and filtered back projection (FBP) were used in C group. Two radiologists
      assessed image quality with 5-piont scale subjectively and double-blind.
      Independent-Sample Test was used to analyze statistical significance of image
      quality including signal to noise ratio(SNR) and contrast to noise ratio (CNR)
      between A and B group or between A and C group. At the same time, Contrast medium
      dose statistical significance between A and B group and mean effective Radiation
      dose (ED)statistical significance between A and C were analyzed by the same way.
      RESULTS: There were no significant difference of image quality including SNR and
      CNR of aortic root (AO), left main coronary artery (LM), left anterior descending
      artery (LAD), circumflex coronary artery (CX) and right coronary artery (RCA)
      Between A and B group (P = non-significant for all comparison), whereas Iodine in
      taken of A group decreased 14% (17 600 mg vs 20 350 mg). There were no
      significant difference of image quality including SNR and CNR of AO, LM, LAD, CX
      and RCA Between A and C group (P = non-significant for all comparison), whereas
      mean ED of A group decreased 50% (0.41 +/- 0.05 mSv vs 0.79 +/- 0.15 mSv).
      CONCLUSION: The double low dose application which use High-pitch spiral mode, 80
      kV, SAFIRE, and Iodixanol (320 mgI/ml) can be used in those patients whose BMI
      <23 kg/m2 and heart rates <65 bpm to reduce the burden of radiation and contrast
      medium significantly, without compromising the image quality.

PMID- 25391865
TI  - [Reduced-dose mode with low-voltage and low contrast agent in coronary artery CT
      angiography-a preliminary study].
AB  - OBJECTIVE: To evaluate image quality of low-voltage coronary artery computed
      tomographic (CT) angiography with low contrast agent in comparison with image
      quality. METHODS: Forty-five patients underwent coronary artery computed
      tomographic (CT) angiography. They were randomly assigned to 3 groups, group A (n
      = 15) were scanned in 120 kVp with 350 mgI/ml iodinated contrast agent mode,
      group B (n = 15) were scanned in 100 kVp with 350 mgI/ml iodinated contrast agent
      mode, group C (n = 15) were scanned in 100 kVp with 270 mgI/ml iodinated contrast
      agent mode. Then measured CT attenuation value of three main branches (RCA, LAD
      and CX) of coronary artery, And compare the SNR, CNR, the effective radiation
      dose(ED) and iodine intake. The Kappa test were used to quantify inter- and intra
      reader agreement in detecting quality of the images under different scanning
      solutions. RESULTS: Three groups of coronary artery CT image quality was no
      statistically significant differences (all P values >0.05), Good inter- and intra
      reader agreement ( k = 0.754, P < 0.05) for the detection of noise in all the
      patients. There was significant difference in the CT attenuation of RCA, LAD and
      CX among the 3 groups (P < 0.05), the CT attenuation was the highest in group B,
      the CT value of RCA, LAD and CX were 537 +/- 90, 505 +/- 90, 484 +/- 75 HU,
      respectively.the CT attenuation was the lowest in group C, the CT value of RCA,
      LAD and CX were 357 +/- 126, 360 +/- 95, 378 +/- 121 HU, respectively. There was
      no significant difference in the SNR and CNR among the 3 groups (P > 0.05). There
      was significant difference in the ED among the 3 groups (P < 0.05). The ED value
      of the group A was bigger than the value of the group B and C. There was no
      significant difference between the group B and C. Compared the group A and B, the
      iodine intake of the group C had fallen by 23%. CONCLUSIONS: The coronary artery
      CT angiography using 100 kVp with 270 mgI/ml iodinated contrast agent provide
      similar objective or subjective image quality compared with the (350 mgI/ml) and
      the 100 kVp (350 mgI/ml), thus enabling effective dose and iodine intake
      reduction without loss of diagnostic information.

PMID- 25391866
TI  - [Low concentration of iodixanol used in CT angiography of lower extremity
      arteriosclerosis obliterans].
AB  - OBJECTIVE: To evaluate the clinical diagnostic value of low concentration of
      iodixanol used in CT angiography (CTA) of lower extremity arteriosclerosis
      obliterans (LEASO). METHODS: 42 patients which were suspect diagnosed with LEASO
      were divided to A group (270 mgI/ml iodixanol, tube voltage 100 kV) and B group
      (350 mgI/ml iohexol, tube voltage 120 kV), 21 patients in each group. Measure the
      body mass index (BMI) before the CTA of lower extremity. CTA results were
      analyzed with the digital subtraction angiography (DSA) as the "gold standard".
      RESULTS: There were no statistical difference of age, gender, BMI and CT value of
      the bifurcation of profunda femoral artery and superficial femoral artery, upper
      segment of anterior tibial artery and posterior tibial artery between A and B
      group. The diagnostic sensitivity and specificity of A and B groups of CTA were
      97.0%, 99.1% and 98.3%, 99.5% for occlusion. Regard artery more than moderate
      stenosis (include moderate stenosis) as the overall statistics, the diagnostic
      sensitivity and specificity of A and B groups of CTA were 99.2%, 99.3% and 99.1%,
      99.3%, the accuracy were 92.9% and 93.0%, the positive predictive and negative
      predictive value were 96.9%, 99.3% and 96.6%, 99.3%, respectively. The kappa
      value of A and B groups of CTA and DSA consistency test were 0.930 and 0.927,
      respectively. CONCLUSION: The CTA with low concentration of iodixanol combine
      with low tube voltage can achieve superior conventional scanning imaging
      features, and has great clinical value in the diagnosis of LEASO, also is an
      effective method for the inspection, evaluation and follow-up.

PMID- 25391867
TI  - [Low-concentration contrast material for dual-source computed tomography coronary
      angiography by a combination of iterative reconstruction and low-tube-voltage
      technique: feasibility study].
AB  - OBJECTIVE: To assess the impact of low concentration contrast media on the degree
      of vascular enhancement, image quality and radiation dose in coronary CT
      angiography (cCTA) studies when using a combination of iterative reconstruction
      and low tube voltage. METHODS: 120 patients who underwent cCTA were randomly
      divided into two groups. The patients in group A received iopromide 370 were
      scanned using the conventional tube output, and images were reconstructed using
      filtered back projection (FBP). The patients in group B received iodixanol 270
      were scanned using the low tube output, and images were reconstructed using
      iterative reconstruction technique (SAFIRE, Siemens Healthcare). CT attenuation
      was measured in the coronary arteries, great arteries, interventricular septum
      and left ventricular cavity. Noise, subjective image quality scores and effective
      radiation dose were compared between the two groups. RESULTS: There was no
      significant difference in the mean CT attenuation achieved, image noise and mean
      image quality score at each anatomic site between iomeprol 270 group and
      iopromide 370 group. The effective radiation dose were 0.44 +/- 0.25 mSv and 0.94
      +/- 0.42 mSv for iomeprol 270 and iopromide 370 in low weight subgroups, and 1.17
      +/- 0.30 mSv and 2.37 +/- 0.66 mSv in high weight subgroups, respectively,
      reflecting dose savings of 53.2% (P < 0.01) and 50.6% (P < 0.01), respectively.
      CONCLUSION: The results demonstrate that with a combination of iterative
      reconstruction and a low tube voltage , a low iodine concentration of 270 mgI/ml
      still improves the contrast enhancement without impairing image quality, as well
      as significantly lowers effective radiation dose.

PMID- 25391868
TI  - [Application of digital orthopedic technology for observing degenerative lumbar
      segmental instability of three-dimensional kinematic characteristics in vivo].
AB  - OBJECTIVE: To explore the characteristics of three-dimensional motion of lumbar
      instability segmental in vivo under physiological weight bearing so as to
      establish three-dimensional diagnostic criteria for degenerative lumbar segmental
      instability (DLSI). METHODS: Eight patients aged 29-65 years with DLSI at L3/4
      were studied as instability group (L3/4), 9 patients aged 51-60 years with DLSI
      at L4/5 as instability group (L4/5) and 10 healthy volunteers aged 26-51 years as
      normal group. Three-dimension (3D) reproductions by matching lumbar spine models
      were reconstructed from thin-section computed tomography scans. Spine motions
      were then reproduced by matching lumber spine models and images from dual
      fluoroscopic imaging system (DFIS). The models were matched to the osseous
      outlines of images from two orthogonal views to determine the SD position of
      vertebrae for each pose. From local coordinate systems at end plates, the motion
      of cephalad vertebrae relative to cauddal vertebrae was calculated for vertebrae
      levels. RESULTS: The motion pattern at L3/4 was altered . During flexion
      extension, migration was significantly larger than normal group along sagittal
      axis (P < 0.05); rotation was significantly larger than normal group along
      vertical axis; migration was significantly smaller than normal group along
      vertical axis; during left-right twisting, rotation was significantly larger than
      normal group along vertical axis (P < 0.05). The motion pattern at L4/5 was also
      altered . During flexion-extension, migrations was significantly larger than
      normal group along sagittal axis (P < 0.05). During left-right twisting,
      migration and rotation were significantly smaller than normal group along
      vertical axis (P < 0.05). Rotation was significantly larger than normal group
      along sagittal axis. During left-right bending, rotation was significantly larger
      than normal group along sagittal axis (P < 0.05). CONCLUSION: Lumbar instability
      segments were significantly different compared with normal lumbar segments. And
      lumbar instability segments (at L3/4) were also different from lumbar instability
      segments (at L4/5). Different three-dimensional diagnostic criteria should be
      formulated for different lumbar instability segments.

PMID- 25391869
TI  - [Effect of wound healing of orthopedic surgery in human immunodeficiency virus
      infected patients with perioperative adjuvant treatments].
AB  - OBJECTIVE: To observe the early wound healing of orthopedic surgery in human
      immunodeficiency virus (HIV) carrier patients treated with optimized auxiliary
      treatments. METHODS: During a period of 48 months, according to the inclusion and
      exclusion criteria plus CD4+ T lymphocyte count, the patients scheduled for
      orthopedic surgery (including HIV positive and negative) were divided into group
      A (HIV positive, CD4<500/ml) with optimized auxiliary treatments, group B (HIV
      positive, CD4 >= 500/ml) and group C (HIV negative) on prophylactic antibiotic
      therapy alone. Wound healing of 3 groups were observed postoperatively. The rates
      of clinical wound infection were compared among 3 groups. RESULTS: A total of 471
      cases (n = 79, HIV+; n = 392, HIV-) were selected due to fresh fracture (n = 544,
      77.28%), fracture of spine (n = 57, 12.31%), mal-union (n = 13, 2.76%), aseptic
      necrosis (n = 15, 3.18%) and osteoarthritis (n = 21, 4.46%). During surgery,
      early open reduction and plate screw internal fixation (group A, n = 23; group B,
      n = 21; group C, n = 274); pedicle screw internal fixation (group A, n = 5; group
      B, n = 6; group C, n = 47); total joint replacement (group A, n = 3; group B, n =
      4; group C, n = 8); interlocking intramedullary nail fixation (group A, n = 7;
      group B, n = 4; group C, n = 35) and other operations (group A, n = 3; group B, n
      = 3; group C, n = 28). For infections, 2 cases (4.88%) were observed in group A,
      3 (5.26%) in group B and 26 (6.63%) in group C. The differences were
      statistically insignificant. CONCLUSION: Reasonable perioperative adjuvant
      treatments, including use of antibiotic, nutritional supports, immunomodulators
      and anti-retroviral drugs, are offered to HIV infected patients undergoing
      orthopedic surgery. Their risks of postoperative wound infection may be
      controlled.

PMID- 25391870
TI  - [Association between exon polymorphisms of BACE2 gene with Alzheimer disease].
AB  - OBJECTIVE: To explore the association between beta-site APP-cleaving enzyme 2
      gene exon polymorphisms with sporadic Alzheimer disease (AD) in a north Chinese
      Han population. METHODS: The exon regions of beta-site APP-cleaving enzyme 2 gene
      were sequenced randomly in 10 sporadic AD patients and 10 healthy controls from
      Beijing and Qinhuangdao, Hebei province during 2000-2008. Using SnaPshot or
      direct sequencing, we genotyped these polymorphisms of 348 sporadic AD patients
      and 294 healthy controls in a Chinese Han population. By genetic statistical
      assay, we studied the association between these polymorphisms and the risks for
      sporadic AD. RESULTS: The sequencing of all exon regions of beta-site APP
      cleaving enzyme 2 gene revealed three polymorphisms of rs2252576C/T, rs1046210C/T
      and rs12149C/T. No association was detected between these three polymorphisms and
      sporadic AD even after statistical adjustments for age, gender and ApoEepsilon4
      status. CONCLUSIONS: There is not a linkage between exon region polymorphisms of
      beta-site APP-cleaving enzyme 2 gene and sporadic AD in a Chinese Han population.

PMID- 25391871
TI  - [Change and significance of blood lipids during the course of carotid artery
      plaque formation induced by diabetes mellitus in patients with ischemic cerebral
      vascular disease].
AB  - OBJECTIVE: To explore the change and possible role of blood lipids during the
      course of plaque formation induced by diabetes mellitus in patients with ischemic
      cerebral vascular disease. METHODS: A total of 1 464 hospitalized patients with a
      diagnosis of ischemic cerebral vascular disease at our department from February
      2008 to May 2012. They were distinguished as plaque (n = 332) or not (n = 132)
      based on carotid artery intima-media thickness (IMT) on B-mode ultrasound. And
      there were diabetics (n = 153) and non-diabetics (n = 311). Also blood glucose,
      blood lipids and new infarction or not were recorded. Comparisons of positive
      carotid artery plaque and the level of blood glucose and lipids were made between
      diabetics and non-diabetics. And the level-risk relationship between plaque
      formation and diabetes mellitus or blood lipids were performed through Logistic
      regression. RESULTS: The positive rate of carotid artery plaque was higher in
      diabetics versus non-diabetics (80% vs 67%, P = 0.003), OR (95% CI, P value) was
      2.001 (1.258-3.182, 0.001) through Logistic regression; after adjusting for
      cerebral infarction, 1.875 (1.172-3.000, 0.009). It had a lower level of high
      density lipoprotein-cholesterol (HDL-C) in diabetics versus non-diabetics (1.1 +/
      0.3 vs 1.2 +/- 0.3 mmol/L, P = 0.001). HDL-C was correlated with plaque
      formation while OR (95% CI, P value) was 0.416 (0.210-0.823, 0.012) through
      Logistic regression. And there has no correlation between plaque formation and
      other subtypes of blood lipids. CONCLUSION: A decrease of HDL-C may play an
      important role in the course of carotid artery plaque induced by diabetes
      mellitus in patients with ischemic cerebral vascular disease.

PMID- 25391872
TI  - [A meta-analysis for the efficacy and safety of drainage after primary total knee
      arthroplasty].
AB  - OBJECTIVE: To evaluate the efficacy and safety of draiange after primary total
      knee arthroplasty (TKA). METHODS: Comparative studies between with and without
      drainage after primary TKA were retrieved from Cochrane Library, PubMed, Medline,
      EMASE, CBM, Highwire, CNKI, VIP and Digital Periodicals in Wanfang Data. All
      randomized controlled trials were included for meta-analysis with RevMan 5.1.5
      software. RESULTS: A total of 9 studies involving 7 in foreign languages and 2 in
      Chinese were identified. There were knee replacement (n = 706), drainage (n =
      359) and non-drainage (n = 347). The results of meta-analysis indicated that no
      inter-group statistical difference existed in the counts of wound infection, deep
      venous thrombosis, hemoglobin value decrease at Day 7 post-operation, knee pain
      at Days 7 and 14 post-operation, post-operative knee range-of-movement or length
      of hospital stay (P > 0.05). And there were statistical differences with respects
      to total blood loss, count of blood transfusions, count of skin ecchymosis,
      increasing rate of knee circumference at Day post-operation (P < 0.05).
      CONCLUSION: Non-routine placement of drainage after primary uncomplicated TKA may
      be preferred. However, for extensive release and primary orthopedics, drainage is
      still necessary. And a surgeon should weigh its pros and cons.

PMID- 25391873
TI  - [Individual surgical treatment of craniocervical junction malformation].
AB  - OBJECTIVE: To explore the individual surgical treatment of various performance
      types of craniocervical junction malformation. METHODS: From January 2011 to
      December 2013, 112 patients with craniocervical junction malformations were
      treated at our department, including Chiari malformation (n = 65) (syringomyelia,
      n = 58 and without syringomyelia, n = 7), basilar invagination disease (n = 35)
      (with cerebellar tonsillar herniation malformation or occipitocervical fusion)
      and complex craniocervical malformation (n = 22) (atlantoaxial dislocation with
      occipitocervical fusion or with chiari malformation or cervical insufficiency sub
      section). All of them had the symptoms of upper cervical nerve damage. For those
      with Chiari malformation, we evaluated atlanto-occipital joint stability
      preoperatively. If atlanto-occipital joint was stable, we performed small
      occipital bone window decompression, partial removal of cerebellar tonsils,
      loosening of posterior fossa, upper cervical adhesions, artificial dura
      appropriate sutured dural repair expanding neck pillow. For patients with basilar
      invagination, if nerve compression performance was in the rear, posterior
      decompression was performed. For those with complex craniocervical malformation
      with atlantoaxial dislocation, neck traction under anesthesia or traction after
      anterior release, then pillow neck fixation and fusion were performed. RESULTS:
      During follow-ups, the symptoms improved significantly (n = 98, 87.51%). There
      were no symptomatic change (n = 10, 8.93%), postoperative neurological
      deterioration (n = 3, 2.67%) and death (n = 1, 0.89%). CONCLUSION: According to
      specific clinical manifestations of craniocervical junction malformation
      patients, the best treatment is to perform individualized surgeries after
      thorough preoperative evaluations.

PMID- 25391874
TI  - [Expressions of aquaporin-4, matrix metallo-proteinase-2 and matrix metallo
      proteinase-14 in peritumor edematous zone of glioma and clinical implications].
AB  - OBJECTIVE: To distinguish the expressions of matrix metallo-poteinase and
      aquaporin in peritumor edematous zone and normal brain tissue for different
      pathological levels of glioma and explore the relationship of glioma cell
      invasiveness and brain edema. METHODS: The immunohistochemical method of SP was
      employed to detect the expressions of aquaporin-4 (AQP-4), matrix metallo
      proteinase-2 (MMP-2) and matrix metallo-proteinase-14 (MMP-14) in glioma and
      normal brain tissue. Due to a rarity of glioma Grades I and II, grades I and II
      glioma were pooled into low malignancy group (LMG) and grades III and IV into
      high malignancy group (HMG). The software program SPSS 11.0 was used for
      Kolmogorov-Smirnov test of independent samplets. The differences were detected
      between normal brain tissue and LMG and HMG. Also the relationship of AQP4, MMP-2
      and MMP-14 was analyzed. RESULTS: With the advancing pathological grades of
      glioma, the expression of AQP-4, MMP-2 and MMP-14 were higher in positive areas.
      There were significant deviations among 3 groups. CONCLUSION: The expressions of
      AQP-4, MMP-2 and MMP-14 in normal brain tissue and all levels of glioma edema are
      positively correlated. And there is a close correlation between glioma
      invasiveness and edema extent.

PMID- 25391875
TI  - [Surgical treatment of lumbar spondylolisthesis by transforaminal lumbar
      interbody fusion].
AB  - OBJECTIVE: To explore the clinical outcomes of transforminal lumbar interbody
      fusion (TLIF) technique in treatment of lumbar spondylolisthesis. METHODS: From
      June 2009 to June 2006, 42 patients underwent TLIF. There were 18 males and 24
      females with an average age of 48 (30-68) years. The preoperative diagnoses
      included lumber degenerative spondylolisthesis (n = 16) and lumbar isthmic
      spondylolisthesis (n = 26). According to the Meyerding standard, 28 cases were
      classified as degreeI, 12 as degree II and 2 as degree III. Posterolateral
      fixation with pedicle screw and decompression, interbody fusion through TLIF
      technical plus cage for distraction reduction were employed. The evaluation
      standards of visual analog scale (VAS) and Oswestry disability index (ODI) were
      applied to evaluate the therapeutic outcomes.Intervertebral height and bone
      fusion were observed by radiology. RESULTS: All patients underwent surgery safely
      without any severe complication. The average follow-up period was 19.4 (9-36)
      months. Compared with preoperative parameters (7.07 +/- 0.92), the postoperative
      scores of VAS decreased significantly (2.52 +/- 1.37) and at the final follow-up
      (2.26 +/- 1.61) (P < 0.05); compared with preoperative parameters (68.43 +/-
      12.81), the postoperative scores of ODI decreased significantly (24.19 +/- 11.44)
      and at the final follow-up (20.86 +/- 9.97) (P < 0.05) and no significant
      difference in VAS or ODI score existed between post-operation and last follow-up
      (P > 0.05). Compared with preoperative parameters (8.25 +/- 1.27), the
      postoperative height of intervertebral space increased significantly (9.68 +/-
      1.62) and at the final follow-up (9.33 +/- 1.25) (P < 0.05). And intervertebral
      height decreased at the final follow-up. There was significant difference between
      post-operation and last follow-up (P = 0.001). At the follow-up of 6.5 months
      postoperatively, all operated segments achieved fusion standard and no broken
      screw. There was 1 case of cage dislocation. CONCLUSION: TLIF may be performed
      easily and safely with fewer complications. And its efficacies are satisfactory
      for patients with lumbar spondylolisthesis.

PMID- 25391876
TI  - [Evolution of brain temperature in ischemic tissues by 1H magnetic resonance
      spectroscopy].
AB  - OBJECTIVE: To explore the application of temperature measurement technique by 1H
      magnetic resonance spectroscopy (MRS) in an ischemia monkey model. METHODS: A MRI
      compatible thermostatic control system was developed. And the equation was
      corrected between brain temperature and the chemical shift of N-acetyl-L-aspartic
      acid (NAA) through in vitro experiment. The normal brain temperature of monkey
      brain was measured. And a monkey model of middle cerebral artery occlusion (MCAO)
      and reperfusion was established. MR diffusion weighted imaging (DWI), perfusion
      weighted imaging (PWI), T2 weighted imaging and 1H MRS were performed at artery
      occlusion stage, 1h, 3h, 6h, 12h and 24h post-recanalization. The brain
      temperatures of different ischemic regions were calculated by the modified brain
      temperature-chemical shift equation. RESULTS: The modified equation was as
      follows: T = 37+100 (CSNAA-2.039). The normal brain temperature was 37.16 
      degrees C. The models were successfully established in 4 monkeys. During arterial
      occlusion stage, the brain temperature of different ischemic tissue was higher
      than the contralateral hemisphere (P < 0.05), including infarct core, ischemic
      penumbra (IP) and oligemic region. And the highest temperature was in IP. After
      recanalization, the brain temperature of infarct core decreased rapidly during an
      early stage and was accompanied by a subsequent increase. However, the brain
      temperature of IP and oligemic region decreased slowly to normal. CONCLUSION: 1H
      MRS may be used to measure brain temperature noninvasively so as to gauge
      ischemic degree.

PMID- 25391877
TI  - [Effects of Kuntai Capsules on endometrial thickness and expressions of leukemia
      inhibitory factor and epidermal growth factor in mouse after controlled ovarian
      hyperstimulation].
AB  - OBJECTIVE: To explore the effects of Kuntai Capsules on endometrial thickness and
      the expressions of leukemia inhibitory factor (LIF) and epidermal growth factor
      (EGF) in mouse after controlled ovarian hyperstimulation. METHODS: Healthy
      Sprague-Dawley mice were randomly allocated into 4 groups of control (group A),
      controlled ovarian hyperstimulation [COH (group B)], COH plus low-dose Kuntai
      Capsules (group C) and COH plus large-dose Kuntai Capsules [2x low-dose (group
      D)]. The controlled ovarian hyperstimulation model was established. The
      endometrial thickness was measured by computerized multi-functional image
      analyzer. And the expressions of LIF and EGF in proliferating endometrium were
      examined by immunohistochemistry. RESULTS: The endometrial thickness of groups C
      and D were higher than that of groups A and B. And there were significant
      differences (P < 0.05). The expression levels of LIF protein in proliferating
      endometrium was weaker than implantation window phase, the expression levels of
      EGF and LIF in group B was weaker than group A, groups C and D stronger than
      groups B and D was stronger than group C. And there were significant differences
      (P < 0.05). CONCLUSION: Kuntai Capsules can promote the growth of endometrium and
      enhance the expression levels of EGF and LIF in mice. And it may improve the
      ability of endometrial receptivity through optimized microenvironment. And a
      larger dose of Kuntai Capsules yields better outcomes.

PMID- 25391878
TI  - [A survey of women undergoing nonmedical induced abortions during 2010-2011 in
      Beijing].
AB  - OBJECTIVE: To explore the population characteristics of women undergoing induced
      abortions and determine high-risk populations for reproductive health services in
      China's metropolises. METHODS: Study subjects were all women undergoing induced
      abortions at a large service center for family planning between January 2010 and
      December 2011 in Beijing. Relevant information was extracted from unified
      registration forms for induced abortions developed by the Ministry of Health,
      including age, permanent residency (Beijing/floating population in Beijing),
      marital status (single/married) and pregnancy history. The population
      characteristics were described. They were then divided into 3 groups according to
      marital status and reproductive history: unmarried, married without children and
      married with children. The population characteristics were further compared among
      three groups, including age, permanent residency, number of abortion and time
      interval between current induced abortion and previous one. RESULTS: A total of
      18 745 women were identified, including 9 601 women undergoing an induced
      abortion in 2010 and 9 144 in 2011. The average age was (27 +/- 6) (14-49) years.
      The women under 20 years accounted for 4.5% (845/18 745), floating women 63.1%
      (11 829/18 745), unmarried 45.0% (8 437/18 745) and women with repeated abortion
      54.2% (10 161/18 745). Among women with repeated abortion, the women whose time
      interval between current abortion and previous one was under 1 year accounting
      for 26% (2 639/10 161) and those with induced abortions more than thrice (39.4%,
      4 006/10 161). The percentage of floating women was the highest in unmarried
      group (P < 0.01). And the percentage for those time interval between current
      abortion and previous one was less than 1 year. And it was also the highest in
      unmarried women among three groups (P < 0.01). CONCLUSION: In Chinese
      metropolitan areas, two-thirds of women with induced abortions is from floating
      population. Approximately a half are unmarried, over a half have induced
      abortions and time interval is the shortest in unmarried women. It suggests that
      reproductive health services for floating and unmarried women should be
      strengthened.

PMID- 25391879
TI  - [Effects of high resting heart rate on the stability of carotid artery plaque in
      a middle and advanced aged population].
AB  - OBJECTIVE: To explore the effect of high resting heart rate (RHR) on the
      stability of carotid artery plaque in a middle and advanced aged population.
      METHODS: During 2010-2011, a total of 5 852 participants were selected randomly
      from 101 510 workers of a Tangshan Kailuan company. RHR was measured and carotid
      artery ultrasound performed to detect the carotid artery plaque. Logistic
      regression was performed to analyze the influencing factors of carotid artery
      stable and unstable plaque. RESULTS: There were 4 894 subjects aged 40-95 years,
      including 2 945 males and 1 949 females. The detection rates of carotid artery
      stable and unstable plaque were 25.7% and 25.4% in low RHR group versus 23.8% and
      33.2% in high RHR group. Compared with low RHR group, the risk of carotid artery
      unstable plaque increased to 29% in high RHR group after adjusting for all
      influencing factors. The odds ratio was 1.290 (95% CI 1.039-1.062). CONCLUSION:
      High RHR can increase the risk of carotid artery unstable plaque in middle and
      advanced aged population.

PMID- 25391880
TI  - Marginal resection for osteosarcoma with effective neoadjuvant chemotherapy: long
      term outcomes.
AB  - BACKGROUND: We report the long-term outcomes of patients with osteosarcoma who
      underwent effective preoperative chemotherapy and subsequently underwent marginal
      resection. METHODS: We reviewed the records of 50 patients with osteosarcoma who
      underwent marginal resection following effective preoperative chemotherapy; 18
      were treated with the MMIA (high-dose methotrexate (HD-MTX), adriamycin (ADR),
      ifosfamide (IFO)) and cisplatin (DDP), and 32 patients were treated with the DIA
      (DDP, ADR and IFO). protocol. The functions of the affected limb were evaluated
      using the revised MSTS93 system. The Kaplan-Meier method was used for survival
      analysis. RESULTS: After a median follow-up of 5.5 years, the rates were: overall
      5-year cumulative survival 61.7%, event-free survival 57.7%, recurrence 8.5%,
      pulmonary metastases 42.6%, and excellent to good function of the affected limb
      57.7%. CONCLUSIONS: Our results showed that marginal resection can be performed
      in patients with osteosarcoma who obtain clinically favorable responses to
      chemotherapy. Patients had a good clinical course and there was no negative
      effect on rates of survival or local recurrence.

PMID- 25391882
TI  - Relative importance of grain boundaries and size effects in thermal conductivity
      of nanocrystalline materials.
AB  - A theoretical model for describing effective thermal conductivity (ETC) of
      nanocrystalline materials has been proposed, so that the ETC can be easily
      obtained from its grain size, single crystal thermal conductivity, single crystal
      phonon mean free path (PMFP), and the Kaptiza thermal resistance. In addition,
      the relative importance between grain boundaries (GBs) and size effects on the
      ETC of nanocrystalline diamond at 300 K has been studied. It has been
      demonstrated that with increasing grain size, both GBs and size effects become
      weaker, while size effects become stronger on thermal conductivity than GBs
      effects.

PMID- 25391881
TI  - Mirolase, a novel subtilisin-like serine protease from the periodontopathogen
      Tannerella forsythia.
AB  - The genome of Tannerella forsythia, an etiological factor of chronic
      periodontitis, contains several genes encoding putative proteases. Here, we
      characterized a subtilisin-like serine protease of T. forsythia referred to as
      mirolase. Recombinant full-length latent promirolase [85 kDa, without its signal
      peptide (SP)] processed itself through sequential autoproteolytic cleavages into
      a mature enzyme of 40 kDa. Mirolase latency was driven by the N-terminal
      prodomain (NTP). In stark contrast to almost all known subtilases, the cleaved
      NTP remained non-covalently associated with mirolase, inhibiting its proteolytic,
      but not amidolytic, activity. Full activity was observed only after the NTP was
      gradually, and fully, degraded. Both activity and processing was absolutely
      dependent on calcium ions, which were also essential for enzyme stability. As a
      consequence, both serine protease inhibitors and calcium ions chelators inhibited
      mirolase activity. Activity assays using an array of chromogenic substrates
      revealed that mirolase specificity is driven not only by the substrate-binding
      subsite S1, but also by other subsites. Taken together, mirolase is a calcium
      dependent serine protease of the S8 family with the unique mechanism of
      activation that may contribute to T. forsythia pathogenicity by degradation of
      fibrinogen, hemoglobin, and the antimicrobial peptide LL-37.

PMID- 25391883
TI  - [Improve of surgical outcomes in spinal fusion surgery : evidence based peri- and
      intra-operative aspects to reduce complications and earlier recovery].
AB  - OBJECTIVES: Because international data have a low level of evidence, a variety of
      treatment approaches for lumbar spine fusion operations are justified based on
      long-established or safety aspects. The aim of this work is to present an
      overview of evidence-based peri- and intraoperative treatment measures to shorten
      the recovery and increase patient satisfaction. MATERIALS AND METHODS: This
      review article is based on a selective literature search that also included
      PubMed on peri- and intraoperative treatment measures for lumbar spinal surgery.
      RESULTS AND DISCUSSION: Peri- and intraoperative treatment algorithms have a
      significant influence on postoperative recovery and patient outcome after lumbar
      spinal surgery. Recent studies show that intraoperative blood loss and blood
      transfusion can be significantly reduced by optimizing patient positioning and
      dorsoventral combined warming measures to maintain body temperature. These
      measures are supplemented by the use of local infiltration of anesthesia and
      vasoconstrictive drugs at the start and high-dose administration of tranexamic
      acid in the early stages of the operation. Use of an epidural catheter
      significantly reduces postoperative, systemic analgesia use and allows rapid
      mobilization to be initiated. Immobilizing drain and corset treatments can be
      limited to complex cases. These treatment measures promote patient satisfaction,
      lead to high-quality, evidence-based care, and contribute to a shorter hospital
      stay and convalescence of the patient.

PMID- 25391884
TI  - Oxidative stress contributes to muscle atrophy in chronic kidney disease
      patients.
AB  - OBJECTIVES: Patients with chronic kidney disease have impaired muscle metabolism,
      resulting in muscle atrophy. Oxidative stress has previously been identified as a
      significant contributor to muscle atrophy in other populations, but the
      contribution in chronic kidney disease is unknown. The aim of this study was to
      investigate the association between oxidative stress, grip strength, and lean
      mass in patients with chronic kidney disease. METHODS: This is a cross-sectional
      study of 152 participants with stage 3 or 4 chronic kidney disease. Outcome
      measures include grip strength, lean mass, plasma total F2-isoprostanes,
      inflammation, peak oxygen uptake, and standard clinical measures. RESULTS: Thirty
      four (22.4%) chronic kidney disease patients had elevated oxidative stress levels
      (plasma F2-isoprostanes >250 pg/ml), with 82% of patients below age-predicted
      grip strength normative values. There was a significant negative association
      between plasma F2-isoprostanes and grip strength (r = -0.251) and lean mass (r = 
      0.243). There were no associations with inflammation markers. Multiple linear
      regression identified plasma F2-isoprostanes as a significant predictor of grip
      strength independent of other predictors: sex, diabetes status, body mass index,
      body fat percent, and phosphate (adjusted r(2) = 69.5, P < 0.001). DISCUSSION:
      Plasma F2-isoprostanes were independently associated with reduced strength in
      chronic kidney disease patients.

PMID- 25391885
TI  - Correlations of platelet-derived microparticles with thromboxane B2, platelet
      activating factor, endothelin-1, and neutrophil to lymphocyte ratio in patients
      with coronary intermediate lesions.
AB  - This study was to investigate the utility of platelet-derived microparticles
      (PMPs) to detect coronary intermediate lesions. Fifty-two patients with coronary
      intermediate lesions and 24 subjects with normal coronary arteries were enrolled.
      In the former group, 31 patients accepted both intravenous ultrasound (IVUS) and
      fractional flow reserve (FFR). Results showed that the level of PMPs was
      significantly higher in the intermediate lesion group and PMPs titer was
      positively correlated with thromboxane B2, platelet activating factor, endothelin
      1, and neutrophil to lymphocyte ratio. The level of PMPs also increased after
      IVUS/FFR, suggesting platelet activation and endothelial dysfunction.

PMID- 25391886
TI  - The effects of association strength and cross-modal correspondence on the
      development of multimodal stimuli.
AB  - In addition to temporal and spatial contributions, multimodal binding is also
      influenced by association strength and the congruency between stimulus elements.
      A paradigm was established in which an audio-visual stimulus consisting of four
      attributes (two visual, two auditory) was presented, followed by questions
      regarding the specific nature of two of those attributes. We wanted to know how
      association strength and congruency would modulate the basic effect that
      responding to same-modality information (two visual or two auditory) would be
      easier than retrieving different-modality information (one visual and one
      auditory). In Experiment 1, association strengths were compared across three
      conditions: baseline, intramodal (100 % association within modalities, thereby
      benefiting same-modality retrieval), and intermodal (100 % association between
      modalities, thereby benefiting different-modality retrieval). Association
      strength was shown to damage responses to same-modality information during
      intermodal conditions. In Experiment 2, association strength was manipulated
      identically, but was combined with cross-modally corresponding stimuli (further
      benefiting different-modality retrieval). The locus of the effect was again on
      responses to same-modality information, damaging responding during intermodal
      conditions but helping responding during intramodal conditions. The potential
      contributions of association strength and cross-modal congruency in promoting
      learning between vision and audition are discussed in relation to a potential
      default within-modality binding mechanism. 

PMID- 25391887
TI  - Endoscopy-assisted transoral resection of parapharyngeal space tumors: a
      retrospective analysis.
AB  - The technique of endoscopy-assisted transoral approach (EATA) has improved
      greatly, which should provide a better alternative for parapharyngeal space (PPS)
      tumors. Here, we compared curative effects between the resection of
      parapharyngeal space (PPS) tumors by EATA and external approaches (EAs),
      including the transcervical, transparotid, and transmandibular approaches. Based
      on the tumors' position and the relationship with adjacent structures, we
      selected 20 patients with parapharyngeal space tumor hospitalized in the Second
      People's Hospital in Shenzhen from January 2008 to December 2013, which were
      divided into the observation group and the control group with patients' informed
      consents. In the observation group, the tumors were removed solely by transoral
      approach under the guidance of endoscopes (EATA), while in the control group, the
      tumors were resected completely using an external approach (EA). We compared the
      total removal rate, the operation time, blood loss, postoperative pain,
      hospitalized time, complication rate, scar, and recurrence between the two
      groups. All the tumors were completely removed and patients were followed up for
      6 months-5 years with no recurrence in either group. There was no significant
      difference regarding total removal rate, operation time, complication rate, and
      recurrence rate between the two groups (P > 0.05). However, significant
      differences were observed in blood loss, hospitalized time, and postoperative
      pain between the two groups (P < 0.05). PPS tumors could be completely removed by
      both EATA and EA. However, EATA has advantages of shortened hospitalized time,
      alleviated blood loss and postoperative pain level, and preservation of facial
      cosmetic.

PMID- 25391888
TI  - Determination of hepatoprotective and antioxidant role of walnuts against ethanol
      induced oxidative stress in rats.
AB  - The aims of our study were the evaluation of the hepatoprotective effect and
      antioxidant role of walnuts against ethanol-induced oxidative stress. The
      hepatoprotective and antioxidant role of the walnuts supplementation feed against
      ethanol-induced oxidative stress were evaluated by measuring liver damage serum
      marker enzymes; aspartate aminotransferase (AST); alanine aminotransferase (ALT);
      gamma glutamyl transpeptidase (GGT); lactate dehydrogenase (LDH); and antioxidant
      defense systems such as reduced glutathione, glutathione reductase, superoxide
      dismutase, glutathione-S-transferase, catalase, and glutathione peroxidase and
      Malondialdehyde (MDA) content in various tissues of rats. Rats were divided into
      six experimental groups: I (control), II (20 % ethanol), III (10 % walnuts), IV
      (20 % ethanol + 10 % walnuts), V (5 % walnuts), and VI (20 % ethanol + 5 %
      walnuts). According to the results, the biochemical analysis showed a
      considerable increase in the serum aspartate AST, ALT, GGT, and LDH in the group
      II as compared to that of group I, whereas decreased in group IVas compared to
      that of group II. In addition, administration of walnuts supplementation restored
      the ethanol-induced imbalance between MDA and fluctuated antioxidant system
      toward close control group particularly in the tissues. The results indicated
      that walnuts could be as important as diet-derived antioxidants in preventing
      oxidative damage in the tissues by reducing the lipid oxidation or inhibiting the
      production of ethanol-induced free radicals in rats. 

PMID- 25391889
TI  - Evaluation of the Etoricoxib-Mediated Pain-Relieving Effect in Patients
      Undergoing Lumbar Fusion Procedures for Degenerative Lumbar Scoliosis: A
      Prospective Randomized, Double-Blind Controlled Study.
AB  - This randomized, double-blind study was carried out to evaluate the effectiveness
      of etoricoxib in controlling the pain during lumbar fusion surgery of the
      degenerative lumbar scoliosis patients. We found that perioperative use of
      etoricoxib produced a significant reduction in the degree of pain compared to the
      patients treated with placebo. Etoricoxib eased the pain and helped to manage the
      discomfort of lumbar fusion surgery. In addition, etoricoxib was well tolerated
      as it caused no serious adverse reaction, suggesting a safe profile. Etoricoxib
      also appeared to ensure and promote the positive effect of surgery, however,
      insignificantly. Thus, the results suggest that etoricoxib was effective in
      safely managing the pain during the lumbar fusion surgery and recovery
      thereafter. 

PMID- 25391890
TI  - Estimation of Some Oxidative Stress Parameters and Blood Pressure After
      Administration of Endothelin-1 (ET-1) in Rats.
AB  - The aim of the study was to investigate changes in the plasma antioxidative
      activity and in lipid peroxidation after administration of endothelin-1 (ET-1)
      and endothelin receptor blockers and additionally, to estimate blood pressure.
      The study was performed on male Wistar rats (n = 6 per group) divided into 4
      groups which received: (1) saline, (2) endothelin-1 (ET-1) (3 MUg/kg b.w.) +
      saline, (3) BQ123 (1 mg/kg) + ET-1 (3 MUg/kg), and (4) BQ788 (3 mg/kg) + ET-1 (3
      MUg/kg b.w.). The endothelin receptor antagonist was injected intravenously 30
      min before ET-1 administration. Blood pressure was monitored, and the blood was
      collected before the saline or ET-1 administration as well as 60 and 300 min
      after their administration. The antioxidative properties were examined by FRAP
      method (ferric reducing ability of plasma), and the concentration of lipid
      peroxidation products was examined by the reaction with thiobarbituric acid
      (TBARS). It was estimated that intravenous administration of endothelin receptor
      blocker ETA increases plasma antioxidative properties (p < 0.01) and parallelly
      decreases the process of lipid peroxidation (p < 0.05 vs. ET-1) and blood
      pressure (p < 0.05).

PMID- 25391891
TI  - Co-transplantation of Hematopoietic Stem Cells and Cxcr4 Gene-Transduced
      Mesenchymal Stem Cells Promotes Hematopoiesis.
AB  - Mesenchymal stem cells (MSCs) are a promising candidate for cellular therapies.
      Co-transplantation of MSCs and hematopoietic stem cells (HSCs) promotes
      successful engraftment and improves hematopoietic recovery. In this study, the
      effects of co-transplantation of HSCs and mouse bone marrow (BM)-derived MSCs
      overexpressing CXCR4 (CXCR4-MSC) on CXCR4-MSC homing capacity and the
      reconstitution potential in lethally irradiated mice were evaluated. Recovery of
      donor-derived peripheral blood leukocytes and platelets was accelerated when
      CXCR4-MSCs were co-transplanted with BM cells. The frequency of c
      kit(+)Sca(+)Lin(-) HSCs was higher in recipient BM following co-transplantation
      of CXCR4-MSCs compared with the EGFP-MSC control and the BMT only groups.
      Surprisingly, the rate of early engraftment of donor-derived BM cells in
      recipients co-transplanted with CXCR4-MSCs was slightly lower than in the absence
      of MSCs on day 7. Moreover, co-transplantation of CXCR4-MSCs regulated the
      balance of T helper cells subsets. Hematopoietic tissue reconstitution was
      evaluated by histopathological analysis of BM and spleen. Co-transplantation of
      CXCR4-MSCs was shown to promote the recovery of hematopoietic organs. These
      findings indicate that co-transplantation of CXCR4-MSCs promotes the early phase
      of hematopoietic recovery and sustained hematopoiesis. 

PMID- 25391892
TI  - The Probable Explanation for the Low Friction of Natural Joints.
AB  - The surface of an articular cartilage, coated with phospholipid (PL) bilayers,
      plays an important role in its lubrication and movement. Intact (normal) and
      depleted surfaces of the joint were modelled and the pH influence on the surface
      interfacial energy, wettability and friction were investigated. In the
      experiments, the deterioration of the PL bilayer was controlled by its
      wettability and the applied friction. The surrounding fluid of an undamaged
      articular cartilage, the synovial fluid, has a pH value of approximately 7.4.
      Buffer solutions were formulated to represent the synovial fluid with various pH
      values. It was found that the surface interfacial energy was stabilised at its
      lowest values when the pH varied between 6.5 and 9.5. These results suggested
      that as the PL bilayers deteriorated, the hydration repulsion mechanism became
      less effective as friction increased. The decreased number of bilayers changed
      the wettability and lowered PL lubricant properties. 

PMID- 25391893
TI  - Simultaneous Bilateral Video-Assisted Thoracoscopic Surgery for the Treatment of
      Primary Spontaneous Pneumothorax.
AB  - We determined the feasibility and clinical efficacy of simultaneous bilateral
      video-assisted thoracoscopic surgery (VATS) for treating primary spontaneous
      pneumothorax (PSP). We performed a retrospective analysis of the efficacy of
      simultaneous bilateral resection of pulmonary bullae using VATS in 21 PSP
      patients that were treated at our hospital from February 2010 to August 2013. We
      found bilateral bullae in all patients through the intraoperative exploration.
      Surgical procedures were successfully completed in all patients without
      conversion to thoracotomy. The mean time of surgery was 128.76 +/- 13.82 min
      (range 100-150 min). Total amount of intraoperative bleeding was 80-200 ml. Total
      drainage of bilateral thoracic ducts was 200-500 ml at the 1st postoperative day
      with a mean drainage of 321.42 +/- 82.66 ml. Bilateral thoracic ducts were
      removed 4-8 days postoperatively with a mean time of 4.7 days. The duration of
      postoperative hospitalization was 5-9 days with a mean duration of 7 days. No
      patient had serious complication(s) and all patients were discharged after full
      recovery. The patients were followed up for 6-18 months after the surgery and no
      relapse occurred. In conclusion, treating the unilateral PSP by simultaneous
      bilateral VATS is safe and effective. It reduces patients' risk of second surgery
      and also minimizes patients' suffering and costs incurred.

PMID- 25391894
TI  - Implications of using on-farm flood flow capture to recharge groundwater and
      mitigate flood risks along the Kings River, CA.
AB  - The agriculturally productive San Joaquin Valley faces two severe hydrologic
      issues: persistent groundwater overdraft and flooding risks. Capturing flood
      flows for groundwater recharge could help address both of these issues, yet flood
      flow frequency, duration, and magnitude vary greatly as upstream reservoir
      releases are affected by snowpack, precipitation type, reservoir volume, and
      flood risks. This variability makes dedicated, engineered recharge approaches
      expensive. Our work evaluates leveraging private farmlands in the Kings River
      Basin to capture flood flows for direct and in lieu recharge, calculates on-farm
      infiltration rates, assesses logistics, and considers potential water quality
      issues. The Natural Resources Conservation Service (NRCS) soil series suggested
      that a cementing layer would hinder recharge. The standard practice of deep
      ripping fractured the layer, resulting in infiltration rates averaging 2.5 in d(
      1) (6 cm d(-1)) throughout the farm. Based on these rates 10 acres are needed to
      infiltrate 1 cfs (100 m(3) h(-1)) of flood flows. Our conceptual model predicts
      that salinity and nitrate pulses flush initially to the groundwater but that
      groundwater quality improves in the long term due to pristine flood flows low in
      salts or nitrate. Flood flow capture, when integrated with irrigation, is more
      cost-effective than groundwater pumping. 

PMID- 25391895
TI  - Clinical diagnostic decision-making in real life contexts: A trans-theoretical
      approach for teaching: AMEE Guide No. 95.
AB  - Making an accurate clinical diagnosis is an essential skill for all medical
      students and doctors, with important implications for patient safety. Current
      approaches for teaching how to make a clinical diagnosis tend to lack the
      complexity that faces clinicians in real-life contexts. In this Guide, we propose
      a new trans-theoretical model for teaching how to make an appropriate clinical
      diagnosis that can be used by teachers as an additional technique to their
      current approach. This educational model integrates situativity theory, dual
      information processing theory and socio-cognitive theory. Mapping and
      microanalysis help the teacher to identify the main processes involved in making
      an accurate clinical diagnosis, so that feedback can be provided that is focused
      on improving key aspects of the skill. An essential aspect of using the new
      educational model is the role of the experienced clinical teacher in making
      judgments about the appropriateness of the learner's attempts to make a clinical
      diagnosis.

PMID- 25391896
TI  - A novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic
      effects against triple-negative breast cancer.
AB  - Vascular endothelial growth factor (VEGF) expression is higher in triple-negative
      breast cancers (TNBC) compared to other subtypes and is reported to predict
      incidence of distant metastases and shorter overall survival. We investigated the
      therapeutic impact of a vaccinia virus (VACV) GLV-1h164 (derived from its parent
      virus GLV-1h100), encoding a single-chain antibody (scAb) against VEGF (GLAF-2)
      in an orthotopic TNBC murine model. GLV-1h164 was tested against multiple TNBC
      cell lines. Viral infectivity, cytotoxicity, and replication were determined.
      Mammary fat pad tumors were generated in athymic nude mice using MDA-MB-231
      cells. Xenografts were treated with GLV-1h164, GLV-1h100, or PBS and followed for
      tumor growth. Viral infectivity was time- and concentration-dependent. GLV-1h164
      killed TNBC cell lines in a dose-dependent fashion with greater than 90%
      cytotoxicity within 4 days at a multiplicity of infection of 5.0. In vitro,
      cytotoxicity of GLV-1h164 was identical to GLV-1h100. GLV-1h164 replicated
      efficiently in all cell lines with an over 400-fold increase in copy numbers from
      the initial viral dose within 4 days. In vivo, mean tumor volumes after 2 weeks
      of treatment were 73, 191, and 422 mm(3) (GLV-1h164, GLV-1h100, and PBS,
      respectively) (p < 0.05). Both in vivo Doppler ultrasonography and immuno
      staining showed decreased neo-angiogenesis in GLV-1h164-treated tumors compared
      to both GLV-1h100 and PBS controls (p < 0.05). This is the first study to
      demonstrate efficient combination of oncolytic and anti-angiogenic activity of a
      novel VACV on TNBC xenografts. Our results suggest that GLV-1h164 is a promising
      therapeutic agent that warrants testing for patients with TNBC.

PMID- 25391897
TI  - Oat1/3 restoration protects against renal damage after ischemic AKI.
AB  - Expression of proximal tubular organic anion transporters Oat1 and Oat3 is
      reduced by PGE2 after renal ischemia and reperfusion (I/R) injury. We
      hypothesized that impaired expression of Oat1/3 is decisively involved in the
      deterioration of renal function after I/R injury. Therefore, we administered
      probenecid, which blocks proximal tubular indomethacin uptake, to abolish the
      indomethacin-mediated restoration of Oat1/3 regulation and its effect on renal
      functional and morphological outcome. Ischemic acute kidney injury (iAKI) was
      induced in rats by bilateral clamping of renal arteries for 45 min with 24-h
      follow-up. Low-dose indomethacin (1 mg/kg) was given intraperitoneally (ip) at
      the end of ischemia. Probenecid (50 mg/kg) was administered ip 20 min later.
      Indomethacin restored the expression of Oat1/3, PAH net secretion, and PGE2
      clearance. Additionally, indomethacin improved kidney function as measured by
      glomerular filtration rate (GFR), renal perfusion as determined by corrected PAH
      clearance, and morphology, whereas it reduced renal cortical apoptosis and nitric
      oxide production. Notably, indomethacin did not affect inflammation parameters in
      the kidneys (e.g., monocyte chemoattractant protein-1, ED1+ cells). On the other
      hand, probenecid blocked the indomethacin-induced restoration of Oat1/3 and
      moreover abrogated all beneficial effects. Our study indicates that the
      beneficial effect of low-dose indomethacin in iAKI is not due to its anti
      inflammatory potency, but in contrast to its restoration of Oat1/3 expression
      and/or general renal function. Inhibition of proximal tubular indomethacin uptake
      abrogates the beneficial effect of indomethacin by resetting the PGE2-mediated
      Oat1/3 impairment, thus reestablishing renal damage. This provides evidence for a
      mechanistic effect of Oat1/3 in a new model of the induction of renal damage
      after iAKI. 

PMID- 25391898
TI  - Activation of ENaC by AVP contributes to the urinary concentrating mechanism and
      dilution of plasma.
AB  - Arginine vasopressin (AVP) activates the epithelial Na(+) channel (ENaC). The
      physiological significance of this activation is unknown. The present study
      tested if activation of ENaC contributes to AVP-sensitive urinary concentration.
      Consumption of a 3% NaCl solution induced hypernatremia and plasma hypertonicity
      in mice. Plasma AVP concentration and urine osmolality increased in hypernatremic
      mice in an attempt to compensate for increases in plasma tonicity. ENaC activity
      was elevated in mice that consumed 3% NaCl solution compared with mice that
      consumed a diet enriched in Na(+) with ad libitum tap water; the latter diet does
      not cause hypernatremia. To determine whether the increase in ENaC activity in
      mice that consumed 3% NaCl solution served to compensate for hypernatremia, mice
      were treated with the ENaC inhibitor benzamil. Coadministration of benzamil with
      3% NaCl solution decreased urinary osmolality and increased urine flow so that
      urinary Na(+) excretion increased with no effect on urinary Na(+) concentration.
      This decrease in urinary concentration further increased plasma Na(+)
      concentration, osmolality, and AVP concentration in these already hypernatremic
      mice. Benzamil similarly compromised urinary concentration in water-deprived mice
      and in mice treated with desmopressin. These results demonstrate that stimulation
      of ENaC by AVP plays a critical role in water homeostasis by facilitating urinary
      concentration, which can compensate for hypernatremia or exacerbate hyponatremia.
      The present findings are consistent with ENaC in addition to serving as a final
      effector of the renin-angiotensin-aldosterone system and blood pressure
      homeostasis, also playing a key role in water homeostasis by regulating urine
      concentration and dilution of plasma. 

PMID- 25391899
TI  - TNF-alpha-mediated cardiorenal injury after rhabdomyolysis in rats.
AB  - The TNF-alpha serum level increases after rhabdomyolysis and is involved in the
      subsequent cardiorenal injury. In the present study, we investigated the TNF
      alpha-dependent cell signaling pathways implicated in cellular injury in these
      organs. Rhabdomyolysis was induced by intramuscular glycerol injection in rats.
      Renal function, cardiac and renal pathology, and activation of caspases were
      evaluated during the first 24 h after glycerol injection. TNF-alpha blockade with
      infliximab reduced tubular necrosis and cardiorenal apoptosis. Cellular Fas
      associated protein with death domain-like IL-1beta-converting enzyme inhibitory
      protein (cFLIP), an inhibitor of caspase-8, was overexpressed in the kidney but
      not in the heart. The inhibitory effect of cFLIP blunted caspase-8 activation in
      the kidney. In this condition, the cellular response to the TNF-alpha stimulus
      was driven to receptor-interacting protein-1 (RIP1)-mediated necroptosis.
      Treatment with RIP1 inhibitor (necrostatin-1) isolated or in combination with
      infliximab showed a similar reduction in tubular necrosis, underscoring the
      importance of TNF-alpha-mediated tubular necroptosis in this model. TNF-alpha
      played a positive regulatory role in the transcription of proapoptotic Bax and
      p53-upregulated modulator of apoptosis (PUMA) proteins. Infliximab treatment
      reduced caspase-9-mediated apoptosis in both organs. Treatment with a caspase-8
      inhibitor showed that caspase-8 participated in the process of apoptosis only in
      the heart, upstream of caspase-9 activation. TNF-alpha-mediated necroptosis is
      the predominant form of tubular injury observed in the glycerol model. TNF-alpha
      up regulates Bax and PUMA proapoptotic proteins, resulting in activation of the
      intrinsic pathway of apoptosis in the kidney and heart. 

PMID- 25391900
TI  - PKC-alpha contributes to high NaCl-induced activation of NFAT5 (TonEBP/OREBP)
      through MAPK ERK1/2.
AB  - High NaCl in the renal medullary interstitial fluid powers the concentration of
      urine but can damage cells. The transcription factor nuclear factor of activated
      T cells 5 (NFAT5) activates the expression of osmoprotective genes. We studied
      whether PKC-alpha contributes to the activation of NFAT5. PKC-alpha protein
      abundance was greater in the renal medulla than in the cortex. Knockout of PKC
      alpha reduced NFAT5 protein abundance and expression of its target genes in the
      inner medulla. In human embryonic kidney (HEK)-293 cells, high NaCl increased PKC
      alpha activity, and small interfering RNA-mediated knockdown of PKC-alpha
      attenuated high NaCl-induced NFAT5 transcriptional activity. Expression of ERK1/2
      protein and phosphorylation of ERK1/2 were higher in the renal inner medulla than
      in the cortex. Knockout of PKC-alpha decreased ERK1/2 phosphorylation in the
      inner medulla, as did knockdown of PKC-alpha in HEK-293 cells. Also, knockdown of
      ERK2 reduced high NaCl-dependent NFAT5 transcriptional activity in HEK-293 cells.
      Combined knockdown of PKC-alpha and ERK2 had no greater effect than knockdown of
      either alone. Knockdown of either PKC-alpha or ERK2 reduced the high NaCl-induced
      increase of NFAT5 transactivating activity. We have previously found that the
      high NaCl-induced increase of phosphorylation of Ser(591) on Src homology 2
      domain-containing phosphatase 1 (SHP-1-S591-P) contributes to the activation of
      NFAT5 in cell culture, and here we found high levels of SHP-1-S591-P in the inner
      medulla. PKC-alpha has been previously shown to increase SHP-1-S591-P, which
      raised the possibility that PKC-alpha might be acting through SHP-1. However, we
      did not find that knockout of PKC-alpha in the renal medulla or knockdown in HEK
      293 cells affected SHP-1-S591-P. We conclude that PKC-alpha contributes to high
      NaCl-dependent activation of NFAT5 through ERK1/2 but not through SHP-1-S591. 

PMID- 25391901
TI  - NOS1-dependent negative feedback regulation of the epithelial sodium channel in
      the collecting duct.
AB  - With an increase in urine flow there is a significant increase in shear stress
      against the renal epithelium including the inner medullary collecting duct,
      resulting in an increase in nitric oxide (NO) production. The mechanisms of the
      shear stress-mediated increases in NO are undetermined. Previous studies found
      that shear stress increases epithelial sodium channel (ENaC) open probability and
      endothelin (ET)-1 production in an ENaC-dependent mechanism in the collecting
      duct (CD). Given that ET-1 stimulates NO production in the CD, we hypothesized
      that shear stress-induced NO production is downstream of shear stress-induced
      ENaC activation and ET-1 production in a negative feedback loop. We determined
      that nitric oxide synthase 1 (NOS1) and NOS3 contribute to shear stress-mediated
      NO production in the CD, that is attenuated by low doses of the ENaC inhibitors
      amiloride and benzamil. Moreover, ETB receptor blockade significantly blunted the
      shear stress-mediated NO production. We further elucidated whether mice lacking
      NOS1 in the collecting duct (CDNOS1KO) have an impaired renal ET-1 system in the
      CD. Although urinary ET-1 production and inner medullary ET receptor expression
      were similar between flox control and CDNOS1KO mice, acute ET-1 treatment
      significantly reduced ENaC open probability in CDs from flox mice but not
      CDNOS1KO mice compared with basal. Basal ENaC activity in CDs was similar between
      the genotypes. We conclude that during acute shear stress across the CD, ENaC
      acts in a negative feedback loop to stimulate NO production in an ETB/NOS1
      dependent manner resulting in a decrease in ENaC open probability and promoting
      natriuresis. 

PMID- 25391903
TI  - Aqueous synthesis of nontoxic Ag2Se/ZnSe quantum dots designing as fluorescence
      sensors for detection of Ag(I) and Cu(II) ions.
AB  - We reported the synthesis of water-soluble and nontoxic Ag(2)Se/ZnSe Quantum Dots
      (QDs) using for fluorescence sensors. The influences of various experimental
      conditions including the synthesis pH, types of ligand, feed ratios, and the
      refluxed time on the growth process and fluorescence of QDs were investigated in
      detail. Under optimal conditions, Ag(2)Se/ZnSe QDs show a single emission peak
      around 490 nm with the maximal photoluminescence (PL) quantum yield (QYs) of 13.7
      %. As-prepared Ag(2)Se/ZnSe QDs can be used for detection of Ag(II) and Cu(II).
      The detection limits are 1 * 10(-6) mol/L to 5 * 10(-5) mol/L for Ag (I), and 2 *
      10(-6) mol/L to 1.10 * 10(-4) mol/L for Cu(II).

PMID- 25391902
TI  - The role of adenosine A1 and A2A receptors in the caffeine effect on MDMA-induced
      DA and 5-HT release in the mouse striatum.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") popular as a designer drug is
      often used with caffeine to gain a stronger stimulant effect. MDMA induces 5-HT
      and DA release by interaction with monoamine transporters. Co-administration of
      caffeine and MDMA may aggravate MDMA-induced toxic effects on DA and 5-HT
      terminals. In the present study, we determined whether caffeine influences DA and
      5-HT release induced by MDMA. We also tried to find out if adenosine A1 and A2A
      receptors play a role in the effect of caffeine by investigating the effect of
      the selective adenosine A1 and A2A receptor antagonists, DPCPX and KW 6002 on DA
      and 5-HT release induced by MDMA. Mice were treated with caffeine (10 mg/kg) and
      MDMA (20 or 40 mg/kg) alone or in combination. DA and 5-HT release in the mouse
      striatum was measured using in vivo microdialysis. Caffeine exacerbated the
      effect of MDMA on DA and 5-HT release. DPCPX or KW 6002 co-administered with MDMA
      had similar influence as caffeine, but KW 6002 was more potent than caffeine or
      DPCPX. To exclude the contribution of MAO inhibition by caffeine in the caffeine
      effect on MDMA-induced increase in DA and 5-HT, we also tested the effect of the
      nonxanthine adenosine receptor antagonist CGS 15943A lacking properties of MAO
      activity modification. Our findings indicate that adenosine A1 and A2A receptor
      blockade may account for the caffeine-induced exacerbation of the MDMA effect on
      DA and 5-HT release and may aggravate MDMA toxicity.

PMID- 25391904
TI  - Closing the MCM cycle at replication termination sites.
AB  - The initiation of eukaryotic DNA replication is a highly regulated process
      conserved from yeast to human. The past decade has seen significant advances in
      understanding how the CMG (Cdc45-MCM-GINS) replicative helicase is loaded onto
      DNA. However, very little was known on how this complex is removed from chromatin
      at the end of S phase. Two papers in a recent issue of Science [1], [2] show that
      in yeast and in Xenopus, the CMG complex is unloaded at replication termination
      sites by an active mechanism involving the polyubiquitylation of Mcm7.

PMID- 25391905
TI  - Tyrosine phosphorylation of LRP6 by Src and Fer inhibits Wnt/beta-catenin
      signalling.
AB  - Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) function as
      transmembrane receptors to transduce Wnt signals. A key mechanism for signalling
      is Wnt-induced serine/threonine phosphorylation at conserved PPPSPxS motifs in
      the LRP6 cytoplasmic domain, which promotes pathway activation. Conserved
      tyrosine residues are positioned close to all PPPSPxS motifs, which suggests they
      have a functional significance. Using a cell culture-based cDNA expression
      screen, we identified the non-receptor tyrosine kinases Src and Fer as novel LRP6
      modifiers. Both Src and Fer associate with LRP6 and phosphorylate LRP6 directly.
      In contrast to the known PPPSPxS Ser/Thr kinases, tyrosine phosphorylation by Src
      and Fer negatively regulates LRP6-Wnt signalling. Epistatically, they function
      upstream of beta-catenin to inhibit signalling and in agreement with a negative
      role in regulating LRP6, MEF cells lacking these kinases show enhanced Wnt
      signalling. Wnt3a treatment of cells enhances tyrosine phosphorylation of
      endogenous LRP6 and, mechanistically, Src reduces cell surface LRP6 levels and
      disrupts LRP6 signalosome formation. Interestingly, CK1gamma inhibits Fer-induced
      LRP6 phosphorylation, suggesting a mechanism whereby CK1gamma acts to de
      represses inhibitory LRP6 tyrosine phosphorylation. We propose that LRP6 tyrosine
      phosphorylation by Src and Fer serves a negative regulatory function to prevent
      over-activation of Wnt signalling at the level of the Wnt receptor, LRP6. 

PMID- 25391906
TI  - Predictors of left atrial coagulation activity among paroxysmal atrial
      fibrillation patients.
AB  - BACKGROUND: The difference between left atrial (LA) and systemic coagulation
      activity in paroxysmal atrial fibrillation (PAF) is unclear. METHODS AND RESULTS:
      We enrolled 100 patients with PAF who underwent AF ablation. Warfarin was stopped
      1 day before the procedure. LA volume index and LA emptying fraction were
      measured by 64-slice multidetector computed tomography. Immediately after
      transseptal puncture, blood samples were simultaneously collected from the LA and
      systemic circulation (SC). In addition, to evaluate the effect of warfarin on D
      dimer levels we recruited an additional 27 PAF patients on continuous warfarin.
      Even in patients with low CHADS2 scores (mean 0.59 +/- 0.68) and during sinus
      rhythm, the prevalence of positive LA-D-dimer (>= 0.5 ug/ml) was greater than
      that of SC-D-dimer (23% vs. 10%, P<0.01). The LA-D-dimer-positive patients had a
      larger mean LA volume index and reduced LA emptying fraction than the LA-D-dimer
      negative patients. Multiple logistic regression analysis revealed that LA volume
      index was independently correlated with positive LA-D-dimer (odds ratio 2.245,
      95% confidence interval 1.194-4.626, P=0.0112). The prevalence of positive LA-D
      dimer was significantly lower in patients taking continuous warfarin, than in
      those on discontinuous warfarin (3.7% vs. 23%, P=0.025). CONCLUSIONS: An enlarged
      LA volume index was associated with high LA coagulation status in patients with
      paroxysmal AF. Adequate warfarin control during AF catheter ablation may reduce
      the prevalence of positive LA-D-dimer.

PMID- 25391907
TI  - New insights for low dosing with the new P2Y12 inhibitors.

PMID- 25391908
TI  - The lead structure does not always work as designed.

PMID- 25391909
TI  - How should we use the wearable cardioverter-defibrillator in Japan?

PMID- 25391910
TI  - Global trend in overweight and obesity and its association with cardiovascular
      disease incidence.
AB  - Although the global prevalence of both the overweight and obese is on the rise,
      there are variations among regions or countries, and sexes. Approximately half or
      more than half of the population are overweight/obese defined as body mass index
      >=25 kg/m(2)in the Americas (61.1%), Europe (54.8%), and Eastern Mediterranean
      (46.0%) according to the World Health Organization, while a much lower prevalence
      is observed in Africa (26.9%), South-East Asia (13.7%), and the Western Pacific
      (25.4%). Females are more likely to be overweight/obese in the Eastern
      Mediterranean, Africa, South-East Asia and the majority of countries in the
      Americas and Western Pacific but not in the most of the countries in Europe.
      These region-sex-ethnicity differences in prevalence may be a clue to the causes
      of the obesity epidemic. Epidemiological studies done in the USA, Europe, and
      Asia found that higher BMI was significantly associated with increased incidence
      of coronary artery disease (CAD) and ischemic stroke, but the association with
      hemorrhagic stroke incidence was not always consistent. The association of BMI
      with CAD and ischemic stroke was generally independent of known mediators, which
      would indicate the importance of controlling or preventing overweight/obesity for
      the prevention of cardiovascular disease.

PMID- 25391911
TI  - Mapping neural connections.
AB  - The technologies needed to map the wiring of the human brain might finally be
      upon us. But the process is still slow, and the data sets are proving difficult
      to manage. Jeffrey Perkel looks at how far connectomics has come and how far it
      still needs to go. 

PMID- 25391912
TI  - Three photons are better than two.
AB  - Three-photon microscopy was suggested in the 1990s, but laser technology at the
      time was just not up to the challenge. Lauren Ware explores how recent technology
      advances are bringing three-photon microscopy back into focus. 

PMID- 25391913
TI  - Marking cells with infrared fluorescent proteins to preserve photoresponsiveness
      in the retina.
AB  - Green fluorescent protein (GFP) and its derivatives are broadly used in
      biomedical experiments for labeling particular cells or molecules. In the mouse
      retina, the light (~500 nm) used to excite GFP can also lead to photoreceptor
      bleaching (peak ~500 nm), which diminishes photoreceptor-mediated synaptic
      transmission in the retinal network. To overcome this problem, we investigated
      the use of infrared fluorescent protein (iRFP) as a marker since it is excited by
      light in the near-infrared range that would not damage the photoresponsiveness of
      the retina. Initially, we tested iRFP expression in human embryonic kidney 293
      (HEK293) cells to confirm that conventional fluorescence microscopy can detect
      iRFP fluorescence. We next introduced the iRFP plasmid into adeno-associated
      virus 2 (AAV-2) and injected the resulting AAV-2 solution into the intraocular
      space. Retinal neurons were found to successfully express iRFP three weeks post
      injection. Light-evoked responses in iRFP-marked cells were assessed using patch
      clamping, and light sensitivity was found to be similar in iRFP-expressing cells
      and non-iRFP-expressing cells, an indication that iRFP expression and detection
      do not affect retinal light responsiveness. Taken together, our results suggest
      iRFP can be a new tool for vision research, allowing for single-cell recordings
      from an iRFP marked neuron using conventional fluorescence microscopy. 

PMID- 25391914
TI  - Two-color fluorescent in situ hybridization using chromogenic substrates in
      zebrafish.
AB  - Two-color fluorescent in situ hybridization (FISH) is a widely used technique for
      comparing relative gene expression patterns. Current two-color FISH protocols are
      not ideal for detecting weakly expressed transcripts or monitoring signal
      strength and background levels during the course of the reaction. Here we
      describe an improved FISH protocol using the conventional highly sensitive
      chromogenic substrates nitro blue tetrazolium (NBT)/5-bromo-4-chloro-3-indolyl
      phosphate (BCIP) and Vector Red in zebrafish embryos. This protocol substantially
      improves on existing FISH techniques by combining the advantages of long
      reactivity of alkaline phosphatase, chromogenic monitoring of both developing
      reactions, and the ability to perform subsequent high-resolution fluorescent
      imaging. Although tested in zebrafish, a similar approach is expected to be
      applicable to ISH in any model organism. 

PMID- 25391915
TI  - DNA profiles from fingermarks.
AB  - Criminal investigations would be considerably improved if DNA profiles could be
      routinely generated from single fingermarks. Here we report a direct DNA
      profiling method that was able to generate interpretable profiles from 71% of 170
      fingermarks. The data are based on fingermarks from all 5 digits of 34
      individuals. DNA was obtained from the fingermarks using a swab moistened with
      Triton-X, and the fibers were added directly to one of two commercial DNA
      profiling kits. All profiles were obtained without increasing the number of
      amplification cycles; therefore, our method is ideally suited for adoption by the
      forensic science community. We indicate the use of the technique in a criminal
      case in which a DNA profile was generated from a fingermark on tape that was
      wrapped around a drug seizure. Our direct DNA profiling approach is rapid and
      able to generate profiles from touched items when current forensic practices have
      little chance of success. 

PMID- 25391916
TI  - Re-use of commercial microfluidics chips for DNA, RNA, and protein
      electrophoresis.
AB  - Microfluidics chip technology is a powerful and convenient alternative to agarose
      gels and PAGE, but costs can be high due to certain chips being non-reusable.
      Here we describe a method to regenerate, re-use, and store Agilent DNA, RNA, and
      protein electrophoresis chips designed for use in the Bioanalyzer 2100. By
      washing the sample wells and displacing the old gel matrix with new gel-dye mix,
      we have run samples on the same chip up to ten times with negligible loss of
      signal quality. Chips whose wells were loaded with buffer or water were stored
      successfully for one week before re-use. 

PMID- 25391917
TI  - Link between retinopathy and nephropathy caused by complications of diabetes
      mellitus type 2.
AB  - While the correlation and chronology of appearance of diabetic nephropathy and
      retinopathy is well known in diabetes mellitus (DM) type 1 patients, in DM type 2
      this correlation is less clear. A retrospective study including 917 patients with
      type 2 diabetes. Diabetic retinopathy (DR) was diagnosed based on fundus
      photographs taken with a non-mydriatic camera. Diabetic nephropathy (DN) was
      diagnosed based on urinary albumin concentration in a morning urine sample.
      Statistical analysis was performed with a seemingly unrelated regression (SUR)
      model. Our SUR model is statistically significant: the test for "model versus
      saturated" is 2.20 and its significance level is 0.8205. The model revealed that
      creatinine and glomerular filtration rate (GFR) have strong influence on
      albuminuria, while body mass index (BMI) and HbA1c have less significant impact.
      DR is affected positively by diabetes duration, insulin treatment, glucose
      levels, and HbA1c, and it is affected negatively by GFR, triglyceride levels, and
      BMI. The association between DR and DN was statistically significant and had a
      unidirectional correlation, which can be explained by chronological order; that
      is, DN precedes DR. The present study indicates that the level of renal
      impairment is proportional to the level of damage to the eye. Furthermore, such
      an association has a chronological aspect; the renal injury precedes retinal
      damage. 

PMID- 25391918
TI  - Disease, communication, and the ethics of (in) visibility.
AB  - As the recent Ebola outbreak demonstrates, visibility is central to the shaping
      of political, medical, and socioeconomic decisions. The symposium in this issue
      of the Journal of Bioethical Inquiry explores the uneasy relationship between the
      necessity of making diseases visible, the mechanisms of legal and visual
      censorship, and the overall ethics of viewing and spectatorship, including the
      effects of media visibility on the perception of particular "marked" bodies.
      Scholarship across the disciplines of communication, anthropology, gender
      studies, and visual studies, as well as a photographer's visual essay and
      memorial reflection, throw light on various strategies of visualization and
      (de)legitimation and link these to broader socioeconomic concerns. Questions of
      the ethics of spectatorship, such as how to evoke empathy in the representation
      of individuals' suffering without perpetuating social and economic inequalities,
      are explored in individual, (trans-)national, and global contexts, demonstrating
      how disease (in)visibility intersects with a complex nexus of health, sexuality,
      and global/national politics. A sensible management of visibility--an "ecology of
      the visible"--can be productive of more viable ways of individual and collective
      engagement with those who suffer.

PMID- 25391919
TI  - Prognosis in very young women with triple-negative breast cancer: retrospective
      study of 216 cases.
AB  - The aim of this investigation was to compare clinical pathological
      characteristics and prognosis of very young and older triple-negative breast
      cancer (TNBC) patients in order to assess their relevance to TNBC in an younger
      population. Data of TNBC patients diagnosed between 2002 and 2007 were
      retrospectively analyzed by computer based chart information. Baseline tumor
      characteristics, biological markers, and patients' prognosis were compared
      between very young (<= 35 years) and older (>35 years) TNBC patients. In the 216
      cases of operable TNBC patients, 48 (22.2%) were <= 35 years and 168 (77.8%) were
      >35 years. Very young TNBC patients had showed a high clinical stage, more
      positive lymph nodes, Ck5/6 and/or EGFR expression (P = 0.049, 0.006, and 0.011,
      respectively). Compared to older TNBC patients, very young TNBC patients have
      short disease-free survival (P = 0.031), while no significant difference was
      found in overall survival (OS) (P = 0.075). In multivariate analysis, lymph node
      metastatic status was a significant predictor of OS. TNBC of very young patients
      is an aggressive breast cancer subtype, but the overall survival of both young
      and older TNBC patients did not have significant differences.

PMID- 25391921
TI  - High ambition.

PMID- 25391920
TI  - Inactivation of RUNX3 predicts poor prognosis in esophageal squamous cell
      carcinoma after Ivor-Lewis esophagectomy.
AB  - The inactivation of RUNX3 in various cancers has been reported while the
      expression of RUNX3 on protein level in esophageal squamous cell carcinoma (ESCC)
      and its relationship with pathological parameters and prognosis still remained
      unclear. In this study, we examined the expression of RUNX3 in 158 ESCC samples
      and 20 normal esophageal mucosa samples by immunohistochemistry and qRT-PCR. The
      IHC result showed that RUNX3 was detected mainly in the nuclei of basal layer
      cells in 18 of 20 normal mucosa samples while in 158 ESCC samples, there were 46
      with RUNX3 nuclei expression, 37 RUNX3 cytoplasmic expression, and 75 negative
      expression. The qRT-PCR confirmed the downregulation of RUNX3 mRNA in the RUNX3
      protein negative group than in the RUNX3 nuclei and cytoplasmic expression group
      (P < 0.001), and the methylation-specific PCR showed a low methylation rate in
      the ESCC tissue samples with RUNX3 protein negative expression (6/40, 15%). The
      RUNX3 nuclei expression negatively correlated with the lymph node metastasis (P =
      0.033) and recurrence status (P = 0.019), and the survival analysis showed that
      the patients with RUNX3 nuclei expression had a higher 5-year survival rate than
      the patients with RUNX3 cytoplasmic/negative expression (P = 0.022). The Cox
      regression analysis showed that the T classification (P = 0.001), lymph node
      metastasis (P < 0.001), and RUNX3 inactivation (negative/cytoplasmic expression,
      P = 0.039) were independent risk factor of poor prognosis. In conclusion, we
      found a frequent inactivation of RUNX3 due to low expression and cytoplasmic
      dislocalization in ESCC. The inactivation of RUNX3 may be involved in the
      progression of ESCC, and RUNX3 could be an indicator of prognosis for patients
      with ESCC after surgery.

PMID- 25391922
TI  - The burden of depression.

PMID- 25391923
TI  - Launch of the Nature Index.

PMID- 25391924
TI  - Help luck along to find psychiatric medicines.

PMID- 25391936
TI  - Italian seismologists cleared of manslaughter.

PMID- 25391937
TI  - Landing on a comet: a guide to Rosetta's perilous mission.

PMID- 25391938
TI  - Edits to ethics code rankle.

PMID- 25391939
TI  - Gut-brain link grabs neuroscientists.

PMID- 25391940
TI  - Ethical dilemma for Ebola drug trials.

PMID- 25391941
TI  - Mental health: the great depression.

PMID- 25391942
TI  - Mental health: a world of depression.

PMID- 25391943
TI  - Medical research: if depression were cancer.

PMID- 25391944
TI  - Depression: a change of mind.

PMID- 25391945
TI  - Mental health: depression needs large human-genetics studies.

PMID- 25391946
TI  - Infectious disease: tough choices to reduce Ebola transmission.

PMID- 25391948
TI  - Q&A: space-time visionary.

PMID- 25391950
TI  - Education: funding plea for rural lab outreach.

PMID- 25391951
TI  - Shale gas: better modelling for the energy mix.

PMID- 25391952
TI  - Scientific collaboration: let poor countries into rich research.

PMID- 25391953
TI  - Data analysis: approximation aids handling of big data.

PMID- 25391954
TI  - European science: EC grant applicants need fuller feedback.

PMID- 25391955
TI  - Depression: the best way forward.

PMID- 25391956
TI  - Condensed-matter physics: magnetic fields without magnetic fields.

PMID- 25391957
TI  - High-temperature superconductivity: electron mirages in an iron salt.

PMID- 25391958
TI  - Neurobiology: building a bigger brain.

PMID- 25391960
TI  - Experimental realization of the topological Haldane model with ultracold
      fermions.
AB  - The Haldane model on a honeycomb lattice is a paradigmatic example of a
      Hamiltonian featuring topologically distinct phases of matter. It describes a
      mechanism through which a quantum Hall effect can appear as an intrinsic property
      of a band structure, rather than being caused by an external magnetic field.
      Although physical implementation has been considered unlikely, the Haldane model
      has provided the conceptual basis for theoretical and experimental research
      exploring topological insulators and superconductors. Here we report the
      experimental realization of the Haldane model and the characterization of its
      topological band structure, using ultracold fermionic atoms in a periodically
      modulated optical honeycomb lattice. The Haldane model is based on breaking both
      time-reversal symmetry and inversion symmetry. To break time-reversal symmetry,
      we introduce complex next-nearest-neighbour tunnelling terms, which we induce
      through circular modulation of the lattice position. To break inversion symmetry,
      we create an energy offset between neighbouring sites. Breaking either of these
      symmetries opens a gap in the band structure, which we probe using momentum
      resolved interband transitions. We explore the resulting Berry curvatures, which
      characterize the topology of the lowest band, by applying a constant force to the
      atoms and find orthogonal drifts analogous to a Hall current. The competition
      between the two broken symmetries gives rise to a transition between
      topologically distinct regimes. By identifying the vanishing gap at a single
      Dirac point, we map out this transition line experimentally and quantitatively
      compare it to calculations using Floquet theory without free parameters. We
      verify that our approach, which allows us to tune the topological properties
      dynamically, is suitable even for interacting fermionic systems. Furthermore, we
      propose a direct extension to realize spin-dependent topological Hamiltonians. 

PMID- 25391959
TI  - Evolution of mosquito preference for humans linked to an odorant receptor.
AB  - Female mosquitoes are major vectors of human disease and the most dangerous are
      those that preferentially bite humans. A 'domestic' form of the mosquito Aedes
      aegypti has evolved to specialize in biting humans and is the main worldwide
      vector of dengue, yellow fever, and chikungunya viruses. The domestic form
      coexists with an ancestral, 'forest' form that prefers to bite non-human animals
      and is found along the coast of Kenya. We collected the two forms, established
      laboratory colonies, and document striking divergence in preference for human
      versus non-human animal odour. We further show that the evolution of preference
      for human odour in domestic mosquitoes is tightly linked to increases in the
      expression and ligand-sensitivity of the odorant receptor AaegOr4, which we found
      recognizes a compound present at high levels in human odour. Our results provide
      a rare example of a gene contributing to behavioural evolution and provide
      insight into how disease-vectoring mosquitoes came to specialize on humans. 

PMID- 25391961
TI  - Observation of topological transitions in interacting quantum circuits.
AB  - Topology, with its abstract mathematical constructs, often manifests itself in
      physics and has a pivotal role in our understanding of natural phenomena.
      Notably, the discovery of topological phases in condensed-matter systems has
      changed the modern conception of phases of matter. The global nature of
      topological ordering, however, makes direct experimental probing an outstanding
      challenge. Present experimental tools are mainly indirect and, as a result, are
      inadequate for studying the topology of physical systems at a fundamental level.
      Here we employ the exquisite control afforded by state-of-the-art superconducting
      quantum circuits to investigate topological properties of various quantum
      systems. The essence of our approach is to infer geometric curvature by measuring
      the deflection of quantum trajectories in the curved space of the Hamiltonian.
      Topological properties are then revealed by integrating the curvature over closed
      surfaces, a quantum analogue of the Gauss-Bonnet theorem. We benchmark our
      technique by investigating basic topological concepts of the historically
      important Haldane model after mapping the momentum space of this condensed-matter
      model to the parameter space of a single-qubit Hamiltonian. In addition to
      constructing the topological phase diagram, we are able to visualize the
      microscopic spin texture of the associated states and their evolution across a
      topological phase transition. Going beyond non-interacting systems, we
      demonstrate the power of our method by studying topology in an interacting
      quantum system. This required a new qubit architecture that allows for
      simultaneous control over every term in a two-qubit Hamiltonian. By exploring the
      parameter space of this Hamiltonian, we discover the emergence of an interaction
      induced topological phase. Our work establishes a powerful, generalizable
      experimental platform to study topological phenomena in quantum systems. 

PMID- 25391962
TI  - Interfacial mode coupling as the origin of the enhancement of T(c) in FeSe films
      on SrTiO3.
AB  - Films of iron selenide (FeSe) one unit cell thick grown on strontium titanate
      (SrTiO3 or STO) substrates have recently shown superconducting energy gaps
      opening at temperatures close to the boiling point of liquid nitrogen (77
      kelvin), which is a record for the iron-based superconductors. The gap opening
      temperature usually sets the superconducting transition temperature Tc, as the
      gap signals the formation of Cooper pairs, the bound electron states responsible
      for superconductivity. To understand why Cooper pairs form at such high
      temperatures, we examine the role of the SrTiO3 substrate. Here we report high
      resolution angle-resolved photoemission spectroscopy results that reveal an
      unexpected characteristic of the single-unit-cell FeSe/SrTiO3 system: shake-off
      bands suggesting the presence of bosonic modes, most probably oxygen optical
      phonons in SrTiO3 (refs 5, 6, 7), which couple to the FeSe electrons with only a
      small momentum transfer. Such interfacial coupling assists superconductivity in
      most channels, including those mediated by spin fluctuations. Our calculations
      suggest that this coupling is responsible for raising the superconducting gap
      opening temperature in single-unit-cell FeSe/SrTiO3. 

PMID- 25391963
TI  - Subduction-driven recycling of continental margin lithosphere.
AB  - Whereas subduction recycling of oceanic lithosphere is one of the central themes
      of plate tectonics, the recycling of continental lithosphere appears to be far
      more complicated and less well understood. Delamination and convective
      downwelling are two widely recognized processes invoked to explain the removal of
      lithospheric mantle under or adjacent to orogenic belts. Here we relate oceanic
      plate subduction to removal of adjacent continental lithosphere in certain plate
      tectonic settings. We have developed teleseismic body wave images from dense
      broadband seismic experiments that show higher than expected volumes of
      anomalously fast mantle associated with the subducted Atlantic slab under
      northeastern South America and the Alboran slab beneath the Gibraltar arc region;
      the anomalies are under, and are aligned with, the continental margins at depths
      greater than 200 kilometres. Rayleigh wave analysis finds that the lithospheric
      mantle under the continental margins is significantly thinner than expected, and
      that thin lithosphere extends from the orogens adjacent to the subduction zones
      inland to the edges of nearby cratonic cores. Taking these data together, here we
      describe a process that can lead to the loss of continental lithosphere adjacent
      to a subduction zone. Subducting oceanic plates can viscously entrain and remove
      the bottom of the continental thermal boundary layer lithosphere from adjacent
      continental margins. This drives surface tectonics and pre-conditions the margins
      for further deformation by creating topography along the lithosphere
      asthenosphere boundary. This can lead to development of secondary downwellings
      under the continental interior, probably under both South America and the
      Gibraltar arc, and to delamination of the entire lithospheric mantle, as around
      the Gibraltar arc. This process reconciles numerous, sometimes mutually
      exclusive, geodynamic models proposed to explain the complex oceanic-continental
      tectonics of these subduction zones. 

PMID- 25391965
TI  - A deep look at synaptic dynamics.

PMID- 25391964
TI  - Radial glia require PDGFD-PDGFRbeta signalling in human but not mouse neocortex.
AB  - Evolutionary expansion of the human neocortex underlies many of our unique mental
      abilities. This expansion has been attributed to the increased proliferative
      potential of radial glia (RG; neural stem cells) and their subventricular
      dispersion from the periventricular niche during neocortical development. Such
      adaptations may have evolved through gene expression changes in RG. However,
      whether or how RG gene expression varies between humans and other species is
      unknown. Here we show that the transcriptional profiles of human and mouse
      neocortical RG are broadly conserved during neurogenesis, yet diverge for
      specific signalling pathways. By analysing differential gene co-expression
      relationships between the species, we demonstrate that the growth factor PDGFD is
      specifically expressed by RG in human, but not mouse, corticogenesis. We also
      show that the expression domain of PDGFRbeta, the cognate receptor for PDGFD, is
      evolutionarily divergent, with high expression in the germinal region of dorsal
      human neocortex but not in the mouse. Pharmacological inhibition of PDGFD
      PDGFRbeta signalling in slice culture prevents normal cell cycle progression of
      neocortical RG in human, but not mouse. Conversely, injection of recombinant
      PDGFD or ectopic expression of constitutively active PDGFRbeta in developing
      mouse neocortex increases the proportion of RG and their subventricular
      dispersion. These findings highlight the requirement of PDGFD-PDGFRbeta
      signalling for human neocortical development and suggest that local production of
      growth factors by RG supports the expanded germinal region and progenitor
      heterogeneity of species with large brains. 

PMID- 25391967
TI  - Differential expression of Toll-like receptor (TLR) and B cell receptor (BCR)
      signaling molecules in primary diffuse large B-cell lymphoma of the central
      nervous system.
AB  - Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL)
      is a distinct and aggressive lymphoma that is confined to CNS. Since, central
      nervous system is barrier-protected and immunologically silent; role of TLR/BCR
      signaling in pathogenesis and biology of CNS DLBCL is intriguing. Genomic
      mutations in key regulators of TLR/BCR signaling pathway (MYD88/CD79B/CARD11)
      have recently been reported in this disease. These observations raised possible
      implications in novel targeted therapies; however, expression pattern of
      molecules related to TLR/BCR pathways in this lymphoma remains unknown. We have
      analyzed the expression of 19 genes encoding TLR/BCR pathways and targets in CNS
      DLBCLs (n = 20) by Nanostring nCounterTM analysis and compared it with expression
      patterns in purified reactive B-lymphocytes and systemic diffuse large B cell
      lymphoma (DLBCL) (n = 20). Relative expression of TLR4, TLR5, TLR9, CD79B and
      BLNK was higher in CNS DLBCLs than in control B-lymphocytes; where as TLR7,
      MALT1, BCL10, CD79A and LYN was lower in CNS DLBCLs (P < 0.0001). When compared
      with systemic DLBCL samples, higher expression of TLR9, CD79B, CARD11, LYN and
      BLNK was noted in CNS DLBCL (>1.5 fold change; P < 0.01). The B cell receptor
      molecules like BLNK and CD79B were also associated with higher expression of
      MYD88 dependent TLRs (TLR4/5/9). In conclusion, we have shown over expression of
      TLR/BCR related genes or their targets, where genomic mutations have commonly
      been identified in CNS DLBCL. We have also demonstrated that TLR over expression
      closely relate with up regulation of genes associated with BCR pathway like
      CD79B/BLNK and CARD11, which play an important role in NF-kB pathway activation.
      Our results provide an important insight into the possibility of TLR and/or B
      cell receptor signaling molecules as possible therapeutic targets in CNS DLBCL.

PMID- 25391968
TI  - Pattern of care of anaplastic oligodendroglioma and oligoastrocytoma in a Korean
      population: the Korean Radiation Oncology Group study 13-12.
AB  - This study investigated the treatment of anaplastic oligodendroglial tumors
      across nine Korean institutions. We reviewed the medical records from 381
      patients with histologically confirmed anaplastic oligodendroglioma or anaplastic
      oligoastrocytoma (AOA) from 2000 to 2010. Clinical factors and treatment patterns
      were analyzed for each year. Post-operative therapy was performed in 354 patients
      (94.1 %), of which 133 received radiotherapy (RT) alone and 189 received both RT
      and chemotherapy. RT alone was the preferred treatment toward the end of the
      study period (29.4 % in 2000-2001 vs. 56.3 % in 2010, P = 0.005). The use of
      procarbazine, lomustine, and vincristine (PCV) decreased (57.6 % in 2000-2001 vs.
      28.6 % in 2010, P = 0.001) and the use of temozolomide (TMZ) increased (0 % in
      2000-2001 vs. 61.9 % in 2010, P < 0.001) over the study period. A combination of
      chemotherapy and RT was used more often than RT alone in young patients (P =
      0.036) and patients with a good performance status (P = 0.023). The 1p/19q co
      deletion status and O-6-methyguanine-DNA methyltransferase methylation were
      analyzed since 2004 but were not significant factors for determining whether to
      administer chemotherapy. Among the patients who received chemotherapy, TMZ was
      used more often in patients with AOA (P = 0.007) and PCV was used more often in
      patients with either multiple lesions (P = 0.027) or the 1p/19q co-deletion (P =
      0.026). Our results demonstrate that the treatment pattern for oligodendroglial
      tumors changed significantly across the study period. In particular, TMZ has
      replaced PCV, and the use of molecular markers as well as RT alone has increased,
      but a unified protocol remains to be established.

PMID- 25391969
TI  - Tissue thioredoxin reductase-1 expression in astrocytomas of different grades.
AB  - Thioredoxin (Trx) is a redox active protein that regulates several physiological
      and biochemical functions, such as growth, apoptosis and cellular defense. The
      function of Trx itself is regulated by thioredoxin reductase (TrxR). Studies
      performed in a variety of human primary tumors have shown that thioredoxin
      reductase 1 (TrxR1) is overexpressed in tumoral tissues compared with
      corresponding normal tissues. This study was designed to determine the expression
      of TrxR1 in astrocytoma tissues of different World Health Organization (WHO)
      grades (grade I-IV). The proliferative (Ki-67) and apoptotic indices of the
      specimens were also investigated for correlation analysis. Astrocytoma tissues
      were extracted from the histopathological specimens of 40 patients. These samples
      included seven histologically normal brain tissues that served as a control group
      and ten tumoral samples for each grade of astrocytoma (grade I-IV). The
      histologically normal brain tissues were obtained from the non-tumoral portions
      of the pathological specimens of grade I (2 cases), grade II (2 cases), grade III
      (2 cases) and grade IV (1 case) astrocytomas. TrxR1 expression was evaluated
      using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and
      immunostaining. The proliferative and apoptotic indices of the specimens were
      investigated by Ki-67 immunostaining and TUNEL assay, respectively. TrxR1
      expression, as assessed by qRT-PCR, increased significantly with astrocytoma
      grade (p = 0.01). The immunostaining intensity of TrxR1 in grade IV astrocytomas
      was significantly greater than that in the control tissue and all other
      astrocytoma grades (p < 0.001). Similarly, immunostaining intensity of TrxR1 in
      the grade III astrocytomas was significantly greater than that in the control
      group and grade I astrocytomas (p < 0.001). All astrocytoma tissues showed more
      intense staining in ascending grades, but the differences between grade I and the
      control, grade II and the control, grades II and I, grades III and II were not
      statistically significant (p > 0.05). Ki-67 index values increased significant in
      accordance with grade progression (p = 0.01). The apoptotic index values were not
      significantly different in any group (p > 0.05); however, the differences between
      grade IV and the control and between grades IV and I were statistically
      significant (p < 0.05). Expression of TrxR1, as assessed by both qRT-PCR and
      immunostaining, correlated highly with both the astrocytoma grade and Ki-67
      index.

PMID- 25391970
TI  - MGMT promoter methylation in non-neoplastic brain.
AB  - O(6)-methylguanine-DNA-methyltransferase (MGMT) is mainly regulated by cytosine
      guanine island promoter methylation that is believed to occur only in neoplastic
      tissue. The present study was undertaken to investigate whether methylation
      occurs also in non-neoplastic brains by collecting 45 non-neoplastic brains from
      autopsies and 56 lobectomy specimens from epileptic surgeries. The promoter
      methylation status of MGMT was studied by methylation-specific polymerase chain
      reaction (MSP) and pyrosequencing (PSQ), while protein expression was studied by
      immunohistochemical stain (IHC). The methylation rates, as determined by MSP and
      PSQ, were 3.0 % (3/101) and 2.9 % (2/69), respectively. Of note, no case had
      positive result concomitantly from both MSP and PSQ (3 were MSP+/PSQ- and 2 were
      MSP-/PSQ+), and all the positive samples were further confirmed by cloning and
      Sanger sequencing. All the methylated cases, except for those having
      indeterminate IHC results from autopsy specimens, revealed no loss of MGMT
      protein expression and similar staining pattern to that of the unmethylated
      cases. In conclusion, the current study demonstrated that MGMT promoter
      methylation could occur in a low percentage of non-neoplastic brains but did not
      affect the status of protein expression, which could be regarded as a normal
      variation in non-neoplastic brains.

PMID- 25391971
TI  - Prediction of giant thermoelectric power factor in type-VIII clathrate Si46.
AB  - Clathrate materials have been the subject of intense interest and research for
      thermoelectric application. Nevertheless, from the very large number of
      conceivable clathrate structures, only a small fraction of them have been
      examined. Since the thermal conductivity of clathrates is inherently small due to
      their large unit cell size and open-framework structure, the current research on
      clathrates is focused on finding the ones with large thermoelectric power factor.
      Here we predict an extraordinarily large power factor for type-VIII clathrate
      Si(46). We show the existence of a large density of closely packed elongated
      ellipsoidal carrier pockets near the band edges of this so far hypothetical
      material structure, which is higher than that of the best thermoelectric
      materials known today. The high crystallographic symmetry near the energy band
      edges for Si(46)-VIII clathrates is responsible for the formation of such a large
      number of carrier pockets.

PMID- 25391972
TI  - How do we maintain competence in aneurysm surgery.

PMID- 25391973
TI  - Stereotactic radiosurgery for cavernous malformations: prejudice from ignorance.

PMID- 25391974
TI  - Anatomic features of glioblastoma and their potential impact on survival.
AB  - BACKGROUND: Many reports on glioblastoma multiforme discuss the prognostic impact
      of anatomical features such as cysts, necrotic changes, extent of edema or
      subependymal spread of tumor cells. In the present study, we examined different
      growth patterns and their possible relations to patient survival. METHODS: To
      analyze whether anatomical characteristics are related to prognosis, we reviewed
      the prospectively collected pre- and postoperative MRIs of 83 patients in the 5
      ALA study, provided by the 5-ALA Glioma Study Group. Following a standardized
      analytic work flow, the tumor volume and site, presence of necrosis or cysts, and
      perifocal edema were assessed preoperatively. In the same way, postoperative MRI
      and the MRI at first recurrence were analyzed. In addition, survival time of the
      patients was documented. RESULTS: Median survival time of all 83 patients was
      15.1 months (range 1.5 to 70.1, mean 18). The site or volume of glioblastoma, as
      well as the presence of intratumoral necrosis or cysts, did not exert a
      significant effect on survival time; 96.4 % of recurrences occurred within the
      former resection margin. Tumors with initial contact with the subependymal zone
      had multifocal or ventricular recurrences significantly more often. In patients
      with residual tumor on early postoperative MRI, the follow-up images displayed
      enlargement of the remnants in 91.9 % of these cases. CONCLUSIONS: A merely
      anatomical analysis of the glioblastoma growth pattern cannot reliably provide
      prognostic information. The occurrence of most recurrences next to the resection
      margin and the high percentage of growing residual tumors underline the
      importance of complete resections.

PMID- 25391975
TI  - First description of pharmacoresistant epilepsy due to independent bilateral
      hypothalamic hamartomas.
AB  - Hypothalamic hamartomas (HHs) are rare developmental malformations consisting of
      mixed neurons and glial cells, usually unilaterally attached to the tuber
      cinereum or mammillary bodies. We report on two patients, both suffering from
      pharmacoresistant epilepsy, behavioural and cognitive disturbances. Ictal and
      interictal electroencephalographic (EEG) abnormalities appeared bilaterally and
      multiregionally with right-sided preponderance. Magnetic-resonance imaging (MRI)
      revealed independent bilateral hypothalamic hamartomas, more prominently on the
      right side. Endoscopic surgery of the right HH was performed in each patient,
      resulting in a significant seizure reduction in both cases. To the best of our
      knowledge, there are no other reports of independent bilateral HHs in the
      literature. 

PMID- 25391976
TI  - Medical student debt and major life choices other than specialty.
AB  - BACKGROUND: Median indebtedness at graduation is now more than $170,000 for
      graduates of US Medical Schools. Debate still exists as to whether higher debt
      levels influence students to choose high paying non-primary care specialties.
      Notably, no previous research on the topic has taken into account cost of
      attendance when constructing a debt model, nor has any research examined the non
      career major life decisions that medical students face. METHODS: Medical students
      were surveyed using an anonymous electronic instrument developed for this study.
      The survey was delivered through a link included in a study email and students
      were recruited from school wide listservs and through snowball sampling (students
      were encouraged to share a link to the survey with other medical students). No
      incentives were offered for survey completion. RESULTS: Responses were recorded
      from 102 US Allopathic medical schools (n=3,032), with 22 institutions (11
      public, 11 private) meeting inclusion criteria of 10% student body response
      proportion (n=1,846). Students with higher debt relative to their peers at their
      home institution reported higher frequencies of feeling callous towards others,
      were more likely to choose a specialty with a higher average annual income, were
      less likely to plan to practice in underserved locations, and were less likely to
      choose primary care specialties. Students with higher aggregate amounts of
      medical student loan debt were more likely to report high levels of stress from
      their educational debt, to delay getting married and to report disagreement that
      they would choose to become a physician again, if given the opportunity to
      revisit that choice. Increases in both aggregate and relative debt were
      associated with delaying having children, delaying buying a house, concerns about
      managing and paying back educational debt, and worrying that educational debt
      will influence one's specialty choice. CONCLUSIONS: Medical student debt and
      particularly debt relative to peers at the same institution appears to influence
      the way that students approach major life choices like when to start a family,
      when to buy a home, and what specialty to choose. Future research should take
      into account cost of attendance when looking for the impact of medical student
      debt on major life choices.

PMID- 25391977
TI  - Matrix metalloproteinase 1, 3, and 9 polymorphisms and esophageal squamous cell
      carcinoma risk.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are multifunctional zinc-dependent
      proteinases that play a fundamental role in the pathogenesis of tumors. We have
      analyzed the association between 3 single-nucleotide polymorphisms (SNPs; MMP1 
      1607 1G/2G, MMP3 -1612 5A/6A, and MMP9 -1562 C/T) and the risk of esophageal
      squamous cell carcinoma (ESCC). MATERIAL/METHODS: We investigated these 3 SNPs in
      132 patients and 132 controls using polymerase chain reaction-restriction
      fragment length polymorphism methods. The MMP1 and MMP3 genes are located on the
      same chromosome. Haplotype analysis was performed to study the combined effect of
      the linked MMP polymorphisms on ESCC risk. RESULTS: The MMP1 and MMP9 promoter
      polymorphisms were not associated with ESCC risk, while the MMP3 -1612 5A/6A
      polymorphism was significantly associated with susceptibility to ESCC. Patients
      carrying the 5A allele had a significantly higher risk for developing ESCC
      compared with individuals carrying the 6A allele (OR=1.93; 95% CI 1.34-2.77;
      p<0.01). The 2G-5A and 1G-5A haplotypes were associated with a significantly
      increased risk of ESCC as compared with the 2G-6A haplotype (OR=2.04, 95% CI 1.37
      3.04 and OR=3.65, 95% CI 1.26-10.55, respectively). CONCLUSIONS: These findings
      implicate this MMP3 polymorphism as a contributor to ESCC susceptibility.

PMID- 25391978
TI  - Laparoscopic complete mesocolic excision with central vascular ligation in right
      colon cancer: Long-term oncologic outcome between mesocolic and non-mesocolic
      planes of surgery.
AB  - AIM: To analyze our experience in translating the concept of total mesorectal
      excision to "no-touch" complete removal of an intact mesocolonic envelope
      (complete mesocolic excision), along with central vascular ligation and apical
      node dissection, in the surgical treatment of right-sided colonic cancers,
      comparing "mesocolic" to less radical "non-mesocolic" planes of surgery in
      respect to quality of the surgical specimen and long-term oncologic outcome.
      METHOD: A total of 115 patients with right-sided colonic cancers were
      retrospectively enrolled from 2008 to 2013 and operated on following the intent
      of minimally invasive complete mesocolic excision with central vascular ligation.
      RESULTS: Morbidity and mortality were 22.6% and 1.7%, respectively. Mesocolic,
      intramesocolic, and muscularis propria planes of resection were achieved in
      65.2%, 21.7%, and 13% of cases, respectively, with significant impact for
      mesenteric plane of surgery on R0 resection rate (97.3%), circumferential
      resection margin <1 mm (2.6%), and consequent survival advantage (82.6% at 5
      years) when compared to muscularis propria plane of surgery, with R0 resection
      rate and overall survival falling to 72% and 60%, respectively, and with
      circumferential resection margin <1 mm raising to 33.3%, all being statistically
      significant. Stratifying patients for stage of disease, laparoscopic complete
      mesocolic excision with central vascular ligation significantly impacted survival
      in patients with stage II, IIIA/B, and in a subgroup of IIIC patients with
      negative apical nodes. CONCLUSION: In our experience, minimally invasive complete
      mesocolic excision with central vascular ligation allows for both safety and
      higher quality of surgical specimens when compared to less radical intramesocolic
      or muscularis propria planes of "standard" surgery, significantly impacting loco
      regional control and thus overall survival.

PMID- 25391979
TI  - The role of resection alone in select children with intracranial ependymoma: the
      Canadian Pediatric Brain Tumour Consortium experience.
AB  - PURPOSE: Gross total resection (GTR) of intracranial ependymoma is an accepted
      goal. More controversial is radiotherapy deferral. This study reports on children
      treated with gross total resection who did not receive upfront adjuvant
      radiotherapy. METHODS: We conducted a retrospective review of children with
      intracranial ependymoma in 12 Canadian centers. Patients who had GTR of their
      tumor and no upfront radiotherapy were identified. Immunostaining was performed
      for Ki-67, epidermal growth factor receptor (EGFR), and EZH2 on archived tissue.
      The Kaplan-Meier survival analysis was performed and compared with those who had
      GTR followed by radiation. RESULTS: Twenty-six children were identified treated
      with GTR alone at diagnosis; 12 posterior fossa ependymoma (PFE) WHO grade II,
      and 14 supratentorial ependymoma (STE). Progression-free survival (PFS) in
      ependymoma treated with GTR alone at diagnosis was inferior in those with high Ki
      67 or positive EZH2 immunostaining. Survival was inferior for patients less than
      2 years old at diagnosis (p = 0.002). Survival was comparable to PFE WHO grade II
      and STE who had GTR followed by radiation (p = 0.62). Five-year PFS and overall
      survival (OS) of those treated with GTR alone were 60 and 70% respectively for
      PFE and 45 and 70% respectively for STE (p = 0.2; 0.55). CONCLUSIONS: This study
      suggests that there is a subset of children with certain biologic features who,
      in the setting of a prospective clinical trial, might be candidates for
      observation following GTR. Good risk factors for this approach include age of 2
      years or older, low Ki-67, and negative EZH2. If relapse occurs, it may be
      confined to the primary site, allowing for possible salvage with GTR followed by
      XRT.

PMID- 25391980
TI  - Healing of rabbit calvarial critical-sized defects using autogenous bone grafts
      and fibrin glue.
AB  - PURPOSE: This study aimed to evaluate ossification of cranial bone defects
      comparing the healing of a single piece of autogenous calvarial bone representing
      a bone flap as in cranioplasty compared to particulated bone slurry with and
      without fibrin glue to represent bone collected during cranioplasty. These defect
      filling materials were then compared to empty control cranial defects. METHODS:
      Ten White New Zealand adult male rabbits had bilateral critical-sized calvarial
      defects which were left either unfilled as control defects or filled with a
      single full-thickness piece of autogenous bone, particulated bone, or
      particulated bone combined with fibrin glue. The defects were left to heal for 6
      weeks postoperatively before termination. CT scans of the calvarial specimens
      were performed. Histomorphometric assessment of hematoxylin-eosin- and Masson
      trichrome-stained specimens was used to analyze the proportion of new bone and
      fibrous tissue in the calvarial defects. RESULTS: There was a statistically
      significant difference in both bone and soft tissue present in all the autogenous
      bone-grafted defect sites compared to the empty negative control defects. These
      findings were supported by CT scan findings. While fibrin glue combined with the
      particulated bone seemed to delay ossification, the healing was more complete
      compared to empty control non-grafted defects. CONCLUSIONS: Autogenous bone
      grafts in various forms such as solid bone flaps or particulated bone treated
      with fibrin glue were associated with bone healing which was superior to the
      empty control defects.

PMID- 25391981
TI  - Growth and reproductive performance of two rabbit breeds reared under intensive
      system in Ghana.
AB  - A study on the growth and reproductive performance of two rabbit breeds was
      undertaken. Data on 588 kits and 97 does of California White and 574 kits and 90
      does of New Zealand White rabbits reared under hot and humid environment in Ghana
      were taken. The reproductive performance of the two breeds, in terms of litter
      size at birth and weaning, litter weight at birth and weaning, kindling interval,
      age at sexual maturity, and gestation length as influenced by breed, season of
      kindling (rainy and dry), year of kindling (2005-2012), and parity (first to
      sixth and over) were determined. The performance of California White in terms of
      litter size at birth, at weaning, kit weight at birth, and age at first kindling
      was 5.9 +/- 0.2, 4.6 +/- 0.1, 54.7 +/- 0.4 g, and 159.8 +/- 0.2 days,
      respectively. That of New Zealand White was 5.9 +/- 0.1, 5.1 +/- 0.1, 55.2 +/-
      1.0 g, and 159.9 +/- 0.2 days, respectively. The results obtained also showed a
      significant breed effects on kit weight at birth, litter weight at weaning, and
      mortality; whereas no significant differences (p > 0.05) were observed between
      the two breeds regarding the other traits measured. Parity had significant
      effects (p < 0.05) on all the growth and reproductive parameters measured with
      the exception of age at first kindling. Year of kindling also had significant
      effect on litter weight at birth, kit weight at birth, and at weaning (p < 0.05)
      but did not have any significant effect on the age at sexual maturity and
      mortality. Season also had significant (p < 0.05) effects on kit weight at birth,
      gestation length, kindling interval, and mortality with better performance
      experienced during the rainy season. 

PMID- 25391983
TI  - Recent advances in H-phosphonate chemistry. Part 2. Synthesis of C-phosphonate
      derivatives.
AB  - This chapter provides an overview of recent advances in the development of new
      methods and protocols for the formation of the P-C bond using H-phosphonate
      diesters as starting materials. Various chemical and stereochemical aspects of
      the transition metal-catalyzed cross-coupling and organocatalyst-promoted
      reactions which are relevant to the synthesis of structurally diverse C
      phosphonate derivatives are surveyed. 

PMID- 25391984
TI  - Laparoscopic parenchymal-sparing liver resection of lesions in the central
      segments: feasible, safe, and effective.
AB  - INTRODUCTION: Here we report the first systematic evaluation of laparoscopic
      parenchymal-sparing segmentectomies for the resection of lesions in the central
      liver segments and the first series of laparoscopic mesohepatectomies. PATIENTS
      AND METHODS: From 1995 to 2012, 482 laparoscopic hepatectomies were performed.
      Thirty-two patients underwent isolated resection of IVa and VIII,
      bisegmentectomies of IVa/IVb and V/VIII, or mesohepatectomy. Sixteen isolated
      resections of IVb or V were excluded. Data was extracted from a retrolective
      database and chart review. Complications were classified (Clavien-Dindo) by three
      independent surgeons. Seventeen patients had colorectal liver metastasis, four
      had neuroendocrine tumors, five had hepatocellular carcinoma, two had GIST, and
      one each had esophageal cancer, breast cancer, and melanoma. Fifteen patients
      underwent anatomic- and 17 non-anatomic wedge resection. Average blood loss was
      403 cc (SD 475), and overall operative time was 183 (SD 106) for hepatectomy and
      253 min (SD 94) for mesohepatectomies. Major complications were mainly
      attributable to synchronous procedures. Mortality, transfusion, and morbidity
      rates were 0, 12, and 37 %, respectively. CONCLUSION: Parenchymal-sparing
      laparoscopic central liver resections and mesohepatectomies are feasible, safe,
      and effective if specific technical details we have learned over time are
      considered. Concomitant procedures should be an exception. This approach exhibits
      an alternative to open surgery while avoiding unnecessary sacrifice of functional
      parenchyma.

PMID- 25391985
TI  - Clinical evaluation of the Asian proximal femur intramedullary nail antirotation
      system (PFNA-II) for treatment of intertrochanteric fractures.
AB  - BACKGROUND: The preferred treatment of intertrochanteric fractures in aged
      patients is controversial. The purpose of the present study was to evaluate the
      outcomes of the Asian proximal femur intramedullary nail antirotation system
      (PFNA-II) for stabilization of such fractures. METHODS: The PFNA-II was used to
      treat intertrochanteric fractures in 163 elderly patients from March 2010 to
      March 2013. The patients comprised 69 men and 94 women with a mean age of 74.7 +/
      13.0 years. All fractures were classified by the Orthopaedic Trauma Association
      classification system; 53, 83, and 27 fractures were classified as 31A1, 31A2,
      and 31A3, respectively. We statistically evaluated the intraoperative blood loss,
      operation time, incision length, X-ray exposure time, and postoperative outcomes.
      Patients were followed up for a mean of 15.2 months (range, 10-24 months).
      Functional outcomes were assessed according to the Harris hip scoring system.
      RESULTS: Statistical analysis revealed an average operation time of 45.7 min
      (range, 35-110 min), average intraoperative blood loss of 115.2 mL (range, 65-430
      mL), X-ray exposure time of 2.7 +/- 1.4 s (range, 2-6 s), and total incision
      length of 6.5 +/- 2.2 cm (range, 5.5-13.0 cm). Patients were followed up for a
      mean of 14.5 months (range, 10-24 months). The neck shaft angle was 134 degrees 
      +/- 15 degrees  (range, 115 degrees -150 degrees ), and the fracture healing time
      was 14.0 +/- 2.5 weeks (range, 11-19 weeks). The Harris hip score was 85.6 +/-
      17.5 points (range, 65-100 points) and included 41 excellent cases (25.15%), 92
      good cases (56.44%), 26 moderate cases (15.95%), and 4 poor cases (2.45%) for a
      positive outcome rate of 81.60%. There were no varus hip deformities, screw
      cutouts, or femoral shaft fractures. Fourteen patients had thigh pain (9.82%),
      and five had inner thigh pain (3.07%); seven had more severe pain that was
      improved by physical therapy. CONCLUSION: PFNA-II has the advantages of a simple
      operation, few complications, and clinical efficacy for the treatment of
      intertrochanteric fractures. However, evaluation of its long-term efficacy and
      risk of other complications requires a large-sample, multicenter observational
      study.

PMID- 25391982
TI  - Prodrugs of phosphonates and phosphates: crossing the membrane barrier.
AB  - A substantial portion of metabolism involves transformation of phosphate esters,
      including pathways leading to nucleotides and oligonucleotides, carbohydrates,
      isoprenoids and steroids, and phosphorylated proteins. Because the natural
      substrates bear one or more negative charges, drugs that target these enzymes
      generally must be charged as well, but small charged molecules can have
      difficulty traversing the cell membrane by means other than endocytosis. The
      resulting dichotomy has stimulated a great deal of effort to develop effective
      prodrugs, compounds that carry little or no charge to enable them to transit
      biological membranes, but able to release the parent drug once inside the target
      cell. This chapter presents recent studies on advances in prodrug forms, along
      with representative examples of their application to marketed and developmental
      drugs. 

PMID- 25391986
TI  - Effects of aflibercept for ranibizumab-resistant neovascular age-related macular
      degeneration and polypoidal choroidal vasculopathy.
AB  - PURPOSE: To evaluate visual and anatomic outcomes in response to the conversion
      of treatment in patients with neovascular age-related macular degeneration (AMD)
      and polypoidal choroidal vasculopathy (PCV) refractory to previous treatment. We
      also investigated the effect of genetic factors. METHODS: We recruited patients
      with AMD or PCV refractory to ranibizumab and initiated aflibercept treatment.
      Changes in the logarithm of minimum angle of resolution (logMAR) and central
      retinal thickness (CRT) measured using optical coherence tomography (OCT) 6
      months after the conversion were compared between the AMD and PCV groups. We also
      genotyped each patient for the ARMS2 A69S, CFH Y402H, and I62V alleles, and
      investigated the association between genotype and treatment response. RESULTS:
      Mean age of the participants was 75.6 +/- 8.0 years. There were 15 patients with
      AMD and 26 patients with PCV. While PCV patients gained about 1 line of vision
      (0.40 +/- 0.37 to 0.31 +/- 0.40, P = 0.003), AMD patients did not show
      significant improvement (0.41 +/- 0.37 to 0.42 +/- 0.39, P = 0.699) despite the
      decrease in CRT (202.1 +/- 113.7 to 131.2 +/- 55.7 MUm, P = 0.003). The
      prevalence of dry retina after treatment was higher among PCV patients (80.8 vs
      46.7 %, P = 0.024). There was no significant difference between patients with
      risk and non-risk alleles for ARMS2 A69S, CFH Y402H, and I62V. CONCLUSION: In AMD
      or PCV patients refractory to ranibizumab, switching to aflibercept is generally
      effective regardless of patient genotype. PCV patients may benefit more
      significantly than AMD patients.

PMID- 25391987
TI  - Quick and facile preparation of visible light-driven TiO2 photocatalyst with high
      absorption and photocatalytic activity.
AB  - Self-doping TiO2 has recently attracted considerable attention for its high
      photocatalytic activity under visible-light irradiation. However, the literature
      reported synthetic methods until now were very time-consuming. In this study, we
      establish a quick and facile method for obtaining self-doping TiO2 with the use
      of directly treated commercial P25 at a desired temperature for only 5 min
      through spark plasma sintering technology. With the using of this method, the
      modified P25 samples exhibit significantly high photoelectric and photocatalytic
      performance. Furthermore, the sample prepared at 600  degrees C exhibits the
      optimum catalytic activity. The photodegradation and H2 evolution rates of this
      samples are significantly higher than those of unmodified P25 sample under
      visible-light irradiation. The physical origin of the visible-light absorption
      for the modified P25 samples is investigated in detail according to their
      structural, optical, and electronic properties. This work will provide a quick
      and facile method for the large-scale synthesis of visible-light driven
      photocatalyst for practical applications.

PMID- 25391988
TI  - Postural tachycardia syndrome, the debate continues....

PMID- 25391989
TI  - Circulating microRNA biomarker studies: pitfalls and potential solutions.
AB  - BACKGROUND: Circulating microRNAs have been proposed as disease biomarkers that
      may aid in risk assessment, diagnosis, prognosis, and monitoring of treatment
      response. The perceived opportunity has loomed particularly large in neoplastic
      disease, where alterations in cancer cells are thought to be reflected in the
      extracellular space as affected cells release upregulated miRNAs or fail to
      release apparently downregulated species. Despite the promise of miRNA
      biomarkers, evaluation of the diagnostic specificity and reproducibility of
      reported markers suggests that realizing this promise remains a work in progress.
      CONTENTS: This review examines issues of diagnostic specificity and
      reproducibility that have afflicted circulating miRNA studies. Surveying the
      breast cancer literature as an example, few miRNAs are reported consistently.
      Furthermore, it is posited that the assumptions underlying models of direct
      contributions of diseased tissue to biofluid miRNA profiles may not hold.
      Suggestions for improving diagnostic specificity and reliability are provided.
      SUMMARY: To maximize the likelihood of return on investment as miRNAs continue to
      be evaluated as specific and clinically useful markers, a focus is needed on
      miRNAs found in specific carriers, such as extracellular vesicles. Alternative
      sampling techniques should be developed, and nonblood biofluids should be
      considered. Careful optimization and standardization of preanalytical and
      analytical methods is needed to ensure that future results, positive or negative,
      are reliable.

PMID- 25391990
TI  - Consenting for molecular diagnostics.

PMID- 25391991
TI  - Sorting the wheat from the chaff in familial hypercholesterolemia.

PMID- 25391992
TI  - Solid lipid microparticles as an approach to drug delivery.
AB  - INTRODUCTION: Solid lipid particles were introduced in the early 1990s as an
      alternative drug carrier system to emulsions, liposomes and polymeric
      microparticles. Although lipid nanoparticles have been the object of a
      substantial number of reviews, fewer are available on lipid microparticles (LMs),
      despite their distinct advantages, including biocompatibility, ease of production
      and characterisation, extended release properties and high loading. AREAS
      COVERED: This review presents an overview of the advantages and drawbacks of LMs,
      that is, lipid-based particles with dimensions in the micrometre range. Specific
      focus is on the role of the main excipients used for LM formulations, lipids and
      surfactants and their effects on LM properties. An update on preparation
      techniques and characterisation methods are also presented, with particular
      emphasis on more recent technologies. The interaction of LMs with biological
      systems and with cells in particular is reviewed. The various LM administration
      routes are examined, with special attention to most recent applications (i.e.,
      pulmonary and nasal delivery). EXPERT OPINION: LMs represent attractive and
      versatile carrier systems; however, their pharmaceutical applicability has been
      rather limited. Investigation on the use of LMs for less-established
      administration routes, such as pulmonary delivery, may provide further interest
      within the area of LM-based systems, both in industry and in the clinic.

PMID- 25391993
TI  - Evaluation of older Chinese people's macronutrient intake status: results from
      the China Health and Nutrition Survey.
AB  - Little is known about the macronutrient intake status of older Chinese people.
      The present study evaluated the macronutrient intake status of older Chinese
      people (aged >= 60 years), investigated whether they had intake levels that met
      the Dietary Reference Intakes (DRI), and explored the associations between
      macronutrient intakes and age groups, sex, education levels, work status, BMI
      groups, urbanicity levels and four socio-economic regions of China (Northeast,
      East Coast, Central and Western). Dietary intake data of 2746 older Chinese with
      complete dietary intake data in the Longitudinal China Health and Nutrition
      Survey (2009 wave) carried out across four diverse regions were analysed. Dietary
      intake data were obtained by interviews using 24 h recalls over three consecutive
      days. The MUFA:SFA ratios were calculated based on the Chinese Food Composition
      Table. Less than one-third of the older Chinese people included in the present
      study had intake levels meeting the adequate intake for carbohydrate-energy and
      fat-energy; less than one-fifth had intake levels meeting the recommended
      nutrient intake for protein-energy; and more than half of the older people had
      fat-energy intakes higher than the DRI. There were strong associations between
      the proportions of energy from the three macronutrients and education levels,
      urbanicity levels and the four socio-economic regions of China, with older people
      living in the East Coast region having different patterns of macronutrient-energy
      intakes when compared with those living in the other three regions. Macronutrient
      intakes across different urbanicity levels in the four regions revealed
      considerable geographical variations in dietary patterns, which will affect the
      risk factors for non-communicable diseases. Clinical interventions and public
      health policies should recognise these regional differences in dietary patterns.

PMID- 25391995
TI  - EphA3 biology and cancer.
AB  - Eph receptor tyrosine kinases control cell-cell interactions during normal and
      oncogenic development, and are implicated in a range of processes including
      angiogenesis, stem cell maintenance and metastasis. They are thus of great
      interest as targets for cancer therapy. EphA3, originally isolated from leukemic
      and melanoma cells, is presently one of the most promising therapeutic targets,
      with multiple tumor-promoting roles in a variety of cancer types. This review
      focuses on EphA3, its functions in controlling cellular behavior, both in normal
      and pathological development, and most particularly in cancer.

PMID- 25391994
TI  - Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced
      erythromycin production in Saccharopolyspora erythraea.
AB  - BACKGROUND: Saccharopolyspora erythraea was extensively utilized for the
      industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic
      commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the
      erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A
      production via the engineering of regulatory genes. RESULTS: By the chromosome
      gene inactivation technique based on homologous recombination with linearized DNA
      fragments, we have inactivated a number of candidate TetR family transcriptional
      regulators (TFRs) and identified one TFR (SACE_7301) positively controlling
      erythromycin biosynthesis in S. erythraea A226. qRT-PCR and EMSA analyses
      demonstrated that SACE_7301 activated the transcription of erythromycin
      biosynthetic gene eryAI and the resistance gene ermE by interacting with their
      promoter regions with low affinities, similar to BldD (SACE_2077) previously
      identified to regulate erythromycin biosynthesis and morphological
      differentiation. Therefore, we designed a strategy for overexpressing SACE_7301
      with 1 to 3 extra copies under the control of PermE* in A226. Following up
      regulated transcriptional expression of SACE_7301, eryAI and ermE, the SACE_7301
      overexpressed strains all increased Er-A production over A226 proportional to the
      number of copies. Likewise, when SACE_7301 was overexpressed in an industrial S.
      erythraea WB strain, Er-A yields of the mutants WB/7301, WB/2*7301 and WB/3*7301
      were respectively increased by 17%, 29% and 42% relative to that of WB. In a 5 L
      fermentor, Er-A accumulation increased to 4,230 mg/L with the highest-yield
      strain WB/3*7301, an approximately 27% production improvement over WB (3,322
      mg/L). CONCLUSIONS: We have identified and characterized a TFR, SACE_7301, in S.
      erythraea that positively regulated erythromycin biosynthesis, and overexpression
      of SACE_7301 in wild-type and industrial S. erythraea strains enhanced Er-A
      yields. This study markedly improves our understanding of the unusual regulatory
      mechanism of erythromycin biosynthesis, and provides a novel strategy towards Er
      A overproduction by engineering transcriptional regulators of S. erythraea.

PMID- 25391997
TI  - [Benign diseases of the esophagogastric junction: A diagnostic and therapeutic
      challenge].

PMID- 25391996
TI  - Expression of the EPHB4 receptor tyrosine kinase in head and neck and renal
      malignancies--implications for solid tumors and potential for therapeutic
      inhibition.
AB  - Solid malignancies are often characterized by overexpression of various receptor
      tyrosine kinases (RTKs) against which many targeted therapies are currently in
      use and in active development. EPHB4 has recently emerged as a frequently
      overexpressed RTK in many types of cancer. Here, we demonstrate expression
      patterns of EPHB4 in two solid malignancies: squamous cell carcinoma of the head
      and neck (HNSCC) and renal cell carcinoma (RCC), by immunohistochemical analysis.
      We demonstrate the first association between EPHB4 expression and progression of
      HNSCC from normal tissue to dysplasia and to cancer. Interestingly, most RCC
      subtypes exhibited expression patterns that were opposite from that found in
      HNSCC, possibly owing to their unique biology and high degree of organ and tumor
      vasculature. Taken together, these results suggest a possible role for EPHB4 as a
      therapeutic target in these malignancies.

PMID- 25391998
TI  - Catheter-related Candida bloodstream infection in intensive care unit patients: a
      subgroup analysis of the China-SCAN study.
AB  - BACKGROUND: In patients hospitalized in intensive care units (ICU), Candida
      infections are associated with increased morbidity, mortality and costs. However,
      previous studies reported confused risk factors for catheter-related Candida
      bloodstream infection (CRCBSI). The objective was to describe the risk factors,
      microbiology, management and outcomes of CRCBSI in the China-SCAN population.
      METHODS: Patients with >=1 Candida-positive peripheral blood culture were
      selected from the China-SCAN study. Peripheral and catheter blood samples were
      collected for Candida isolation. Patients with the same strain of Candida in
      peripheral and catheter blood samples were considered as being with CRCBSI, while
      patients with Candida-positive peripheral blood cultures only or different
      strains were considered as non-CRCBSI. Data were collected from the China-SCAN
      study. RESULTS: CRCBSI incidence in ICU was 0.03% (29/96,060), accounting for
      9.86% of all candidemia observed in ICU (29/294). The proportion of CRCBSI due to
      Candida parapsilosis reached 33.3%, more than that of Candida albicans (28.6%).
      In univariate analyses, older age (P=0.028) and lower body weight (P=0.037) were
      associated with CRCBSI. Multivariate analysis showed that the sequential organ
      failure assessment (SOFA) score was independently associated with CRCBSI (odds
      ratio (OR)=1.142, 95% confidence interval = 1.049-1.244, P=0.002). Catheter
      removal and immune enhancement therapy were often used for CRCBSI treatment.
      CONCLUSIONS: In China, CRCBSI was more likely to occur in old patients with low
      body weight. SOFA score was independently associated with CRCBSI. Candida
      parapsilosis accounted for a high proportion of CRCBSI, but the difference from
      non-CRCBSI was not significant.

PMID- 25391999
TI  - Developing a framework to review near-miss maternal morbidity in India: a
      structured review and key stakeholder analysis.
AB  - BACKGROUND: In India there is a thrust towards promoting institutional delivery,
      resulting in problems of overcrowding and compromise to quality of care. Review
      of near-miss obstetric events has been suggested to be useful to investigate
      health system functioning, complementing maternal death reviews. The aim of this
      project was to identify the key elements required for a near-miss review
      programme for India. METHODS: A structured review was conducted to identify
      methods used in assessing near-miss cases. The findings of the structured review
      were used to develop a suggested framework for conducting near-miss reviews in
      India. A pool of experts in near-miss review methods in low and middle income
      countries (LMICs) was identified for vetting the framework developed. Opinions
      were sought about the feasibility of implementing near-miss reviews in India, the
      processes to be followed, factors that made implementation successful and the
      associated challenges. A draft of the framework was revised based on the experts'
      opinions. RESULTS: Five broad methods of near-miss case review/audit were
      identified: Facility-based near-miss case review, confidential enquiries,
      criterion-based clinical audit, structured case review (South African Model) and
      home-based interviews. The opinion of the 11 stakeholders highlighted that the
      methods that a facility adopts should depend on the type and number of cases the
      facility handles, availability and maintenance of a good documentation system,
      and local leadership and commitment of staff. A proposed framework for conducting
      near-miss reviews was developed that included a combination of criterion-based
      clinical audit and near-miss review methods. CONCLUSION: The approach allowed for
      development of a framework for researchers and planners seeking to improve
      quality of maternal care not only at the facility level but also beyond,
      encompassing community health workers and referral. Further work is needed to
      evaluate the implementation of this framework to determine its efficacy in
      improving the quality of care and hence maternal and perinatal morbidity and
      mortality.

PMID- 25392001
TI  - How a new funding model will shift allocations from the Global Fund to Fight
      AIDS, tuberculosis, and malaria.
AB  - Policy makers deciding how to fund global health programs in low- and middle
      income countries face important but difficult questions about how to allocate
      resources across countries. In this article we present a typology of three
      allocation methodologies to align allocations with priorities. We then apply our
      typology to the Global Fund to Fight AIDS, Tuberculosis, and Malaria. We examined
      the Global Fund's historical HIV allocations and its predicted allocations under
      a new funding model that creates an explicit allocation methodology. We found
      that under the new funding model, substantial shifts in the Global Fund's
      portfolio are likely to result from concentrating resources in countries with
      more HIV cases and lower per capita incomes. For example, South Africa, which had
      15.8 percent of global HIV cases in 2009, could see its Global Fund HIV funding
      more than triple, from historic levels that averaged 3.0 percent to 9.7 percent
      of total Global Fund allocations. The new funding model methodology is expected,
      but not guaranteed, to improve the efficiency of Global Fund allocations in
      comparison to historical practice. We conclude with recommendations for the
      Global Fund and other global health donors to further develop their allocation
      methodologies and processes to improve efficiency and transparency.

PMID- 25392000
TI  - Structural insight into amino group-carrier protein-mediated lysine biosynthesis:
      crystal structure of the LysZ.LysW complex from Thermus thermophilus.
AB  - In the biosynthesis of lysine by Thermus thermophilus, the metabolite alpha
      ketoglutarate is converted to the intermediate alpha-aminoadipate (AAA), which is
      protected by the 54-amino acid acidic protein LysW. In this study, we determined
      the crystal structure of LysZ from T. thermophilus (TtLysZ), an amino acid kinase
      that catalyzes the second step in the AAA to lysine conversion, which was in a
      complex with LysW at a resolution of 1.85 A. A crystal analysis coupled with
      isothermal titration calorimetry of the TtLysZ mutants for TtLysW revealed tight
      interactions between LysZ and the globular and C-terminal extension domains of
      the LysW protein, which were mainly attributed to electrostatic forces. These
      results provided structural evidence for LysW acting as a protecting molecule for
      the alpha-amino group of AAA and also as a carrier protein to guarantee better
      recognition by biosynthetic enzymes for the efficient biosynthesis of lysine. 

PMID- 25392002
TI  - Does previous stone treatment in children generate a disadvantage or just the
      opposite?
AB  - In this study we aimed to determine the effects of previous open renal surgery,
      percutaneous nephrolithotomy and extracorporeal shockwave lithotripsy (ESWL) on
      the results and complications of subsequent percutaneous nephrolithotomy (PCNL)
      in pediatric patients. We reviewed the files of all 105 patients with 116 renal
      units (RU) undergoing PCNL at two main institutions between December 2000 and
      February 2014. The 116 RUs were divided into four groups: primary PCNL patients
      with 44 RU (37.9%) were categorized as group 1, 29 RU (25%) with a history of
      failed ESWL on the same side were categorized as group 2, 23 RU (19.8%) with
      previous PCNL surgery were categorized as group 3 and 20 RU (17.2%) with open
      renal surgery were categorized as group 4. Patient characteristics, mean
      operative time, mean fluoroscopy time, time to access the collecting system,
      hemoglobin change, number of more than 1 access, stone-free rates, postoperative
      hospitalization time and complications in four groups were compared. There were
      no differences between the groups in age, sex, mean stone size and stone
      laterality. Mean operative time, mean fluoroscopy time, time to access the
      collecting system, hemoglobin change, complication rates, number of more than one
      access hospitalization times were similar in the each group (p > 0.05 for each
      parameter). The stone-free rates after PCNL were 81.8% in group 1, 79.3% in group
      2, 78.3% in group 3 and 80 % in group 4 (p = 0.67). Percutaneous nephrolithotomy
      is effective and safe in children who have previously had open nephrolithotomy,
      history of ESWL or PCNL without no more complications than are seen with primary
      PCNL of kidneys and with similar success rate.

PMID- 25392003
TI  - Xenx (Xenolith): preliminary considerations of a new "all-in-one" ureteral
      guidewire and anti-repulsion device.
AB  - A new anti-retropulsion device for the endoscopic treatment of ureteral stones
      was evaluated for safety and potential efficacy. The XenxTM (Rocamed, Monaco
      Montecarlo) is an anti-retropulsion device that operates as a normal hydrophilic
      guidewire when "closed" and as a nitinol ureteral mesh when "open". We performed
      semirigid ureterorenoscopy and Ho:YAG Laser lithotripsy in 15 patients, with a
      single ureteral stone. For each procedure, the papilla was negotiated with the
      XenxTM, the radiopaque markers were positioned over the stone via direct
      visualization and the device was opened under fluoroscopic control. The
      ureteroscope was then retracted and reinserted beside the XenxTM. At the end of
      the procedure, the XenxTM was closed, and a ureteral catheter was coaxially
      placed and left for 24-48 h post-operation. We evaluated device positioning
      success with respect to pushability, ease of deployment, full expansion and
      fitting with the ureteral walls, kink resistance and stone retention capabilities
      during lithotripsy and device retrieval. Operative time, post-operative
      complications (Clavien-Dindo scale), ultrasound kidney stone-free rate and the
      hydronephrosis grade, were also recorded. At 4 weeks post-operation, the stone
      free rate was assessed via non-contrast computed tomography with 1-mm slices. All
      procedures were successfully accomplished without complications according to the
      Clavien-Dindo scale. In all the cases, XenxTM was inserted successfully past the
      stone and opened over it. In 4/15 cases (27%) some difficulties in pushability
      and kink resistance were recorded. In no case stone fragment basketing was
      performed. The median operative time was 24 min. At hospital discharge, 14/15
      patients (93%) were kidney stone-free. At 4 weeks, the NCCT stone-free rate was
      100%. This study demonstrated that the XenxTM is safe and effective in terms of
      the stone-free rate, complications and operating time. Moreover, use of the
      XenxTM allows the use of a basket or guide wire to be avoided.

PMID- 25392004
TI  - An Apparently Classical Case Report of Sturge-Weber Syndrome.
AB  - Sturge-Weber syndrome is a rare, sporadic, congenital neurocutaneous syndrome,
      likely due to abnormal development of the cephalic microvasculature. Symptoms and
      signs depend on the extent and location of the venous dysplasia. We describe a
      case of a 33-year-old woman presenting with drug-resistant epilepsy, chronic
      headache, and recurring nonepileptic seizures. Computed tomography and magnetic
      resonance imaging scans showed severe frontoparietal right hemisphere atrophy,
      prevalent right frontoparietal leptomeningeal enhancement, circumscribed angioma
      of the left rolandic sulcus, and prominent deep venous system. We report an
      apparently classical Sturge-Weber syndrome and hypothesize a shared
      pathophysiologic mechanism for clinical symptoms. We speculate that all the main
      symptoms observed in our patient could be the expression of a functional
      imbalance between the atrophic right hemisphere and the hyperexcitable left
      cortex. 

PMID- 25392005
TI  - Global Synchronization of Multichannel EEG in Patients With Electrical Status
      Epilepticus in Sleep.
AB  - In the research field of epilepsy, it is a challenge to understand the transition
      of brain activity to electrical status epilepticus in sleep (ESES). In this
      study, an S-estimator method is proposed to describe the course of global
      synchronization in multichannel electroencephalograph (EEG) from awake to sleep
      in 11 patients with ESES. The study confirms that there is a significant increase
      in spikes and global synchronization from awake to sleep. It is also found that
      global synchronization is strongly correlated with spikes. The proposed method
      has the potential of revealing the intrinsic features of EEG signals and the
      underlying brain dynamics in ESES. 

PMID- 25392006
TI  - Artificial bee colony algorithm for single-trial electroencephalogram analysis.
AB  - In this study, we propose an analysis system combined with feature selection to
      further improve the classification accuracy of single-trial electroencephalogram
      (EEG) data. Acquiring event-related brain potential data from the sensorimotor
      cortices, the system comprises artifact and background noise removal, feature
      extraction, feature selection, and feature classification. First, the artifacts
      and background noise are removed automatically by means of independent component
      analysis and surface Laplacian filter, respectively. Several potential features,
      such as band power, autoregressive model, and coherence and phase-locking value,
      are then extracted for subsequent classification. Next, artificial bee colony
      (ABC) algorithm is used to select features from the aforementioned feature
      combination. Finally, selected subfeatures are classified by support vector
      machine. Comparing with and without artifact removal and feature selection, using
      a genetic algorithm on single-trial EEG data for 6 subjects, the results indicate
      that the proposed system is promising and suitable for brain-computer interface
      applications. 

PMID- 25392007
TI  - How the Individual Alpha Peak Frequency Helps Unravel the Neurophysiologic
      Underpinnings of Behavioral Functioning in Children With Attention
      Deficit/Hyperactivity Disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) has been associated with an
      elevated resting-state theta/beta power ratio and elevated theta power. However,
      the potential confounding effect of a low individual alpha peak frequency (IAPF)
      on the theta-power estimate has often been disregarded when studying the
      relationship between ADHD and the theta/beta power ratio or theta power alone.
      The aim of the present study was to assess whether the theta/beta power ratio and
      relative theta power are correlated with behavioral functioning in children with
      ADHD, as expected from previous studies. Subsequently, the influence of IAPF and
      the amount of supposed overlap between the individually determined alpha-band and
      the fixed theta-band were studied. For 38 children (aged 8-15 years),
      electroencephalographic (EEG) and investigator-scored ADHD Rating Scale IV data
      were available. Additional neurocognitive data were available for 32 children. As
      expected, the theta/beta power ratio and theta were positively related to the
      ADHD core symptoms. This relationship strengthened when controlling for IAPF,
      although correlations did not significantly differ from one another. Eight of 38
      children (21%) showed a supposed overlap between their individually determined
      alpha band and the theta band. Neurocognitive performance did not show any
      relationship with the theta/beta power ratio or theta. The results of this study
      confirm that the theta/beta power ratio and theta power are indeed correlated
      with behavioral symptoms in children with ADHD and underscore the relevance of
      taking the IAPF into account. 

PMID- 25392008
TI  - Disruption of the Posterior Medial Network during the Acute Stage of Transient
      Global Amnesia: A Preliminary Study.
AB  - Acute perturbation of the corticohippocampal circuitry is a primary
      pathophysiological mechanism underlying transient global amnesia (TGA). With
      regard to memory, 2 distinct corticohippocampal circuitries potentially exist:
      the anterior temporal network and the posterior medial network. We used
      electroencephalography (EEG) spectral analysis to determine which network is
      disrupted during the acute stage of TGA. Patients with TGA who visited Seoul
      National University Bundang Hospital within 24 hours after symptom onset were
      retrospectively identified. Twenty patients underwent EEG twice, once in the
      acute stage (<24 hours after symptom onset) and once in the resolved stage (>2
      months after symptom onset). A fast Fourier transform was applied to compute the
      spectral power of the 6 frequency bands: delta, theta, alpha, beta 1, beta 2, and
      gamma. We assumed that the frontocentral and temporal regions belonged to the
      anterior temporal network, whereas the parieto-occipital regions belonged to the
      posterior medial network. A paired Student's t test was used to evaluate the
      difference in the regional spectral powers in each frequency band between the
      acute and resolved TGA stages. Compared with the resolved stage, relative theta
      power in the left parieto-occipital region was increased and relative alpha power
      in the right parieto-occipital region was reduced during the acute stage of TGA,
      with a statistical significance of P<.05 (uncorrected). The cortical regions that
      belonged to the posterior medial network showed alterations of neuronal activity,
      which reflects disruption of the posterior medial network during the acute stage
      of TGA.

PMID- 25392009
TI  - X-ray microscopy as an approach to increasing accuracy and efficiency of serial
      block-face imaging for correlated light and electron microscopy of biological
      specimens.
AB  - The recently developed three-dimensional electron microscopic (EM) method of
      serial block-face scanning electron microscopy (SBEM) has rapidly established
      itself as a powerful imaging approach. Volume EM imaging with this scanning
      electron microscopy (SEM) method requires intense staining of biological
      specimens with heavy metals to allow sufficient back-scatter electron signal and
      also to render specimens sufficiently conductive to control charging artifacts.
      These more extreme heavy metal staining protocols render specimens light opaque
      and make it much more difficult to track and identify regions of interest (ROIs)
      for the SBEM imaging process than for a typical thin section transmission
      electron microscopy correlative light and electron microscopy study. We present a
      strategy employing X-ray microscopy (XRM) both for tracking ROIs and for
      increasing the efficiency of the workflow used for typical projects undertaken
      with SBEM. XRM was found to reveal an impressive level of detail in tissue
      heavily stained for SBEM imaging, allowing for the identification of tissue
      landmarks that can be subsequently used to guide data collection in the SEM.
      Furthermore, specific labeling of individual cells using diaminobenzidine is
      detectable in XRM volumes. We demonstrate that tungsten carbide particles or
      upconverting nanophosphor particles can be used as fiducial markers to further
      increase the precision and efficiency of SBEM imaging. 

PMID- 25392010
TI  - The Effect of an Electronic Checklist on Critical Care Provider Workload, Errors,
      and Performance.
AB  - PURPOSE: The strategy used to improve effective checklist use in intensive care
      unit (ICU) setting is essential for checklist success. This study aimed to test
      the hypothesis that an electronic checklist could reduce ICU provider workload,
      errors, and time to checklist completion, as compared to a paper checklist.
      METHODS: This was a simulation-based study conducted at an academic tertiary
      hospital. All participants completed checklists for 6 ICU patients: 3 using an
      electronic checklist and 3 using an identical paper checklist. In both scenarios,
      participants had full access to the existing electronic medical record system.
      The outcomes measured were workload (defined using the National Aeronautics and
      Space Association task load index [NASA-TLX]), the number of checklist errors,
      and time to checklist completion. Two independent clinician reviewers, blinded to
      participant results, served as the reference standard for checklist error
      calculation. RESULTS: Twenty-one ICU providers participated in this study. This
      resulted in the generation of 63 simulated electronic checklists and 63 simulated
      paper checklists. The median NASA-TLX score was 39 for the electronic checklist
      and 50 for the paper checklist (P = .005). The median number of checklist errors
      for the electronic checklist was 5, while the median number of checklist errors
      for the paper checklist was 8 (P = .003). The time to checklist completion was
      not significantly different between the 2 checklist formats (P = .76).
      CONCLUSION: The electronic checklist significantly reduced provider workload and
      errors without any measurable difference in the amount of time required for
      checklist completion. This demonstrates that electronic checklists are feasible
      and desirable in the ICU setting.

PMID- 25392011
TI  - Differential Mycobacterium bovis BCG vaccine-derived efficacy in C3Heb/FeJ and
      C3H/HeOuJ mice exposed to a clinical strain of Mycobacterium tuberculosis.
AB  - The global epidemic caused by the bacterial pathogen Mycobacterium tuberculosis
      continues unabated. Moreover, the only available vaccine against tuberculosis,
      Mycobacterium bovis bacillus Calmette-Guerin (BCG), demonstrates variable
      efficacy. To respond to this global threat, new animal models that mimic the
      pathological disease process in humans are required for vaccine testing. One new
      model, susceptible C3Heb/FeJ mice, is similar to human tuberculosis in that these
      animals are capable of forming necrotic tubercle granulomas, in contrast to
      resistant C3H/HeOuJ mice. In this study, we evaluated the impact of prior BCG
      vaccination of C3Heb/FeJ and C3H/HeOuJ mice on exposure to a low-dose aerosol of
      Mycobacterium tuberculosis W-Beijing strain SA161. Both BCG-vaccinated murine
      strains demonstrated reduced bacterial loads 25 days after infection compared to
      controls, indicating vaccine efficacy. However, during chronic infection, vaccine
      efficacy waned in C3H/HeOuJ but not in C3Heb/FeJ mice. Protection in vaccinated
      C3Heb/FeJ mice was associated with reduced numbers of CD11b(+) Gr1(+) cells,
      increased numbers of effector and memory T cells, and an absence of necrotic
      granulomas. BCG vaccine efficacy waned in C3H/HeOuJ mice, as indicated by reduced
      expression of gamma interferon (IFN-gamma) and increased expressions of
      interleukin-17 (IL-17), IL-10, and Foxp3 by T cells compared to C3Heb/FeJ mice.
      This is the first murine vaccine model system described to date that can be
      utilized to dissect differential vaccine-derived immune efficacy. 

PMID- 25392012
TI  - Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination.
AB  - The Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination,
      was developed by I. Vodopija and colleagues of the Zagreb Institute of Public
      Health in Croatia in the 1980s. It was recommended by WHO as one of the
      intramuscular (IM) schedules for rabies vaccination in 2010. We reviewed the
      literature on the immunogenicity, safety, economic burden, and compliance of the
      Zagreb 2-1-1 regimen. Compared to Essen, another IM schedule recommended by WHO,
      Zagreb has higher compliance, lower medical cost, and better immunogenicity at an
      early stage. 

PMID- 25392013
TI  - Seroprevalence of Cytomegalo Virus (CMV) among pregnant women in Thika, Kenya.
AB  - BACKGROUND: The fetal consequences of CMV infection have made it one of the most
      serious infections contracted during pregnancy. Despite the posed teratogenic
      risk during pregnancy, there is no national screening test for CMV infection is
      available during pregnancy in Kenya. Thus little is known on its epidemiological
      data that is necessary for health planners and care providers. METHODS: A cross
      sectional study was conducted at Thika district level 5 hospital, Kenya to
      investigate seroprevalence of CMV infections and associated possible risk factors
      among pregnant women. Structured questionnaires were used to gather socio
      demographic data and ELISA was used to detect CMV infections using IgG and IgM.
      RESULTS: Out of 260 pregnant women, 201 (77.3%) were CMV IgG 21(8.1%) CMV IgM
      being on acute stage of the disease. Marital status (OR = 3.7533, 95% CI =3.0231
      6.9631, P < 0.0001), parity (OR = 3.7533, 95% CI = 3.0231-6.9631, P < 0.0001),
      and education (OR = 3.7533, 95% CI = 3.0231-6.9631, P < 0.0001), history of blood
      transfusion (OR = 0.0374, 95% CI = 0.00120-0.1168, OR = 0.3804) were found to
      significantly influence seropostivity in univariate analysis. CONCLUSION: The
      88.4% CMV prevalence rate being detected among pregnant women calls for vaccine
      and routine screening for CMV infections and its associated risk factors in this
      kind of settings.

PMID- 25392015
TI  - PDE-5 inhibitors: clinical points.
AB  - Erectile dysfunction is usually of vascular origin and is frequently encountered
      in men with cardiovascular disease. The introduction of phosphodiesterase-5
      inhibitors has revolutionized the management of patients with erectile
      dysfunction. Currently available phosphodiesterase-5 inhibitors have distinct
      pharmacokinetic and pharmacodynamic properties, thus permitting for tailoring
      sexual therapy according to patient characteristics and needs. Phosphodiesterase
      5 inhibitors possess vasorelaxing properties and exert systemic hemodynamic
      effects, which need to be taken into account when other cardiovascular drugs are
      co-administered. Special caution is needed with alpha-blockers, while the co
      administration with nitrates is contra-indicated due to the risk of life
      threatening hypotension. This review presents the advent of sexual therapy,
      describes the mechanism of action and the specific characteristics of
      commercially available phosphodiesterase-5 inhibitors, summarizes the efficacy
      and safety of these drugs with special emphasis on the cardiovascular system, and
      discusses the clinical criteria used for the selection of each drug for the
      individual patient. 

PMID- 25392017
TI  - Local perceptions, RUSLEFAC mapping, and field results: the sediment budget of
      cocagne river, new brunswick, Canada.
AB  - Erosion and sedimentation in water courses represent a major and costly problem
      everywhere on the planet. Perception of local actors of the state of the river
      can be a useful source of information to document the river's changes. The main
      objective of this study consists of understanding how multiple data sources can
      be used for identifying the most sensitive areas subject to erosion and
      sedimentation in a watershed. To achieve our objective we combined three
      complementary methods: conducting interviews, estimating the most sensitive soil
      loss areas using the Revised Universal Soil Loss Equation for Application in
      Canada (RUSLEFAC) and taking measurements of environmental variables (turbidity,
      deposition rate, particle size, water quality, rainfall). The information
      gathered from the interviews allowed us to determine which areas were the most
      affected (e.g., either erosion or deposition). However, we observed that there
      were some differences between the areas identified by the participants and those
      obtained from the RUSLEFAC and in situ measurements. Among these differences,
      participants identified sites which were the results of misuse or bad practices
      (e.g., ATV). By contrast sensitive sites for erosion, as identified using
      RUSLEFAC, are instead areas of steep slopes, located near the river without
      forest cover. The in situ measurements were very helpful in establishing
      background values for turbidity but also for comparing quantitative information
      (e.g., particle size) with what was reported in the interviews. 

PMID- 25392014
TI  - Molecular pathophysiology of priapism: emerging targets.
AB  - Priapism is an erectile disorder involving uncontrolled, prolonged penile
      erection without sexual purpose, which can lead to erectile dysfunction. Ischemic
      priapism, the most common of the variants, occurs with high prevalence in
      patients with sickle cell disease. Despite the potentially devastating
      complications of this condition, management of recurrent priapism episodes
      historically has commonly involved reactive treatments rather than preventative
      strategies. Recently, increasing elucidation of the complex molecular mechanisms
      underlying this disorder, principally involving dysregulation of nitric oxide
      signaling, has allowed for greater insights and exploration into potential
      therapeutic targets. In this review, we discuss the multiple molecular regulatory
      pathways implicated in the pathophysiology of priapism. We also identify the
      roles and mechanisms of molecular effectors in providing the basis for potential
      future therapies. 

PMID- 25392018
TI  - The role of composition, invasives, and maintenance emissions on urban forest
      carbon stocks.
AB  - There are few field-based, empirical studies quantifying the effect of invasive
      trees and palms and maintenance-related carbon emissions on changes in urban
      forest carbon stocks. We estimated carbon (C) stock changes and tree maintenance
      related C emissions in a subtropical urban forest by re-measuring a subsample of
      residential permanent plots during 2009 and 2011, using regional allometric
      biomass equations, and surveying residential homeowners near Orlando, FL, USA.
      The effect of native, non-native, invasive tree species and palms on C stocks and
      sequestration was also quantified. Findings show 17.8 tC/ha in stocks and 1.2
      tC/ha/year of net sequestration. The most important species both by frequency of
      C stocks and sequestration were Quercus laurifolia Michx. and Quercus virginiana
      Mill., accounting for 20% of all the trees measured; 60% of carbon stocks and
      over 75% of net C sequestration. Palms contributed to less than 1% of the total C
      stocks. Natives comprised two-thirds of the tree population and sequestered 90%
      of all C, while invasive trees and palms accounted for 5 % of net C
      sequestration. Overall, invasive and exotic trees had a limited contribution to
      total C stocks and sequestration. Annual tree-related maintenance C emissions
      were 0.1% of total gross C sequestration. Plot-level tree, palm, and litter cover
      were correlated to C stocks and net sequestration. Findings can be used to
      complement existing urban forest C offset accounting and monitoring protocols and
      to better understand the role of invasive woody plants on urban ecosystem service
      provision.

PMID- 25392019
TI  - Conservation tillage affects species composition but not species diversity: a
      comparative study in Northern Italy.
AB  - Conservation tillage (CT) is widely considered to be a practice aimed at
      preserving several ecosystem functions. In the literature, however, there seems
      to be no clear pattern with regard to its benefits on species diversity and
      species composition. In Northern Italy, we compared species composition and
      diversity of both vascular plants and Carabids under two contrasting tillage
      systems, i.e., CT and conventional tillage, respectively. We hypothesized a
      significant positive impact of CT on both species diversity and composition. We
      also considered the potential influence of crop type. The tillage systems were
      studied under open field conditions with three types of annual crops (i.e.,
      maize, soybean, and winter cereals), using a split-plot design on pairs of
      adjacent fields. Linear mixed models were applied to test tillage system, crop,
      and interaction effects on diversity indices. Plant and Carabids communities were
      analyzed by multivariate methods (CCA). On the whole, 136 plant and 51 carabid
      taxa were recorded. The two tillage systems studied did not differ in floristic
      or carabid diversity. Species composition, by contrast, proved to be
      characteristic for each combination of tillage system and crop type. In
      particular, CT fields were characterized by nutrient demanding weeds and the
      associated Carabids. The differences were especially pronounced in fields with
      winter cereals. The same was true for the flora and Carabids along the field
      boundaries. For studying the effects of CT practices on the sustainability of
      agro-ecosystems, therefore, the focus should be on species composition rather
      than on diversity measures. 

PMID- 25392020
TI  - Insulin requirement profiles in Japanese hospitalized subjects with type 2
      diabetes treated with basal-bolus insulin therapy.
AB  - To assess the total daily inulin dose (TDD) and contribution of basal insulin to
      TDD and to identify the predictive factors for insulin requirement profiles in
      subjects with type 2 diabetes, we retrospectively examined insulin requirement
      profiles of 275 hospitalized subjects treated with basal-bolus insulin therapy
      (BBT) (mean age, 60.1 +/- 12.9 years; HbA1c, 10.2 +/- 4.5%). Target plasma
      glucose level was set between 80 and 129 mg/dL before breakfast and between 80
      and 179 mg/dL at 2-hour after each meal without causing hypoglycemia. We also
      analyzed the relationship between the insulin requirement profiles (TDD and
      basal/total daily insulin ratio [B/TD ratio]) and insulin-associated clinical
      parameters. The mean TDD was 0.463 +/- 0.190 unit/kg/day (range, 0.16-1.13
      unit/kg/day). The mean B/TD ratio was 0.300 +/- 0.099 (range, 0.091-0.667). A
      positive correlation of TDD with B/TD ratio was revealed by linear regression
      analysis (r=0.129, p=0.03). Stepwise multiple regression analysis identified post
      breakfast glucose levels before titrating insulin as an independent determinant
      of the insulin requirement profile [Std beta (standard regression coefficient) =
      0.228, p<0.01 for TDD, Std beta = -0.189, p<0.01 for B/TD ratio]. The TDD was
      <0.6 unit/kg/day and the B/TD ratio was <0.4 in the majority (70.2%) of subjects
      in the present study. These findings may have relevance in improving glycemic
      control and decreasing the risk of hypoglycemia and weight gain in subjects with
      type 2 diabetes treated with BBT. 

PMID- 25392021
TI  - Age-related changes in the diurnal variation of ketogenesis in patients with type
      2 diabetes and relevance to hypoglycemic medications.
AB  - To assess the significance of ketogenesis in the management of diabetes mellitus,
      we analyzed the factors associated with the diurnal variation of the plasma
      ketone body levels. The subjects consisted of 220 patients with type 2 diabetes,
      aged 60 +/- 15 years, without advanced complications. They ate a standardized,
      low-fat meal at 8:00, 12:00, and 18:00. The plasma levels of 3-hydroxybutyrate
      (3HB) and free fatty acid (FFA) were increased before breakfast and before
      dinner. The plasma glucose concentration was almost the same at any blood
      sampling time point among age quartiles. However, the 3HB levels were
      significantly decreased with age, which was most obvious before dinner. The FFA
      levels also decreased with age, but the decline was mild. A multiple regression
      analysis with stepwise selection revealed that age was an independent, negative
      contributor and that the pre-breakfast FFA concentration was an independent,
      positive contributor to the pre-breakfast 3HB levels. Regarding the pre-dinner
      3HB levels, in addition to age and the pre-dinner FFA concentration, the uses of
      sulfonylurea and dipeptidyl peptidase-4 inhibitors were independent negative
      contributors. The metabolism of ketone bodies is an alternative energy source for
      the brain under conditions of starvation. While excessive ketogenesis leads to
      critical ketoacidosis, inadequate ketone body production could be associated with
      a propensity to develop neurohypoglycemia in elderly patients treated with
      insulin secretagogues. Because age-related changes in ketogenesis were the most
      significant before dinner, attention should be paid not only to fasting but also
      to the pre-dinner levels of 3HB. 

PMID- 25392022
TI  - Isotretinoin exposure during pregnancy: a population-based study in The
      Netherlands.
AB  - OBJECTIVE: To estimate isotretinoin exposure in Dutch pregnant women despite the
      implemented pregnancy prevention programme (PPP) and second, to analyse the
      occurrence of adverse fetal or neonatal outcomes in these isotretinoin exposed
      pregnancies. DESIGN: Population-based study. SETTING: The Netherlands.
      PARTICIPANTS: A cohort of 203,962 pregnancies with onset between 1 January 1999
      and 1 September 2007 consisting of 208,161 fetuses or neonates. MAIN OUTCOME
      MEASURES: Isotretinoin exposure in the 30 days before or during pregnancy.
      Proportions of adverse fetal or neonatal outcomes, defined as intrauterine deaths
      >=16 week of gestation and neonates with major congenital anomalies. ORs with 95%
      CIs adjusted for maternal age were calculated to estimate the risk of adverse
      fetal or neonatal outcome after maternal isotretinoin exposure. RESULTS: 51
      pregnancies, 2.5 (95% CI 1.9 to 3.3) per 10,000 pregnancies, were exposed to
      isotretinoin despite the pregnancy prevention programme. Forty-five of these
      pregnancies, 2.2 (95% CI 1.6 to 2.9) per 10,000 pregnancies, were exposed to
      isotretinoin during pregnancy and six additional women became pregnant within 30
      days after isotretinoin discontinuation. In 60% of isotretinoin exposed
      pregnancies, women started isotretinoin while already pregnant. In five out of
      the 51 isotretinoin exposed pregnancies (53 fetuses), 9.4% (95% CI 1.3% to
      17.6%), had an adverse fetal or neonatal outcome. The OR for adverse fetal or
      neonatal outcomes after isotretinoin exposure in 30 days before or during
      pregnancy was 2.3 (95% CI 0.9 to 5.7) after adjustment for maternal age.
      CONCLUSIONS: Although a PPP was already implemented in 1988, we showed that
      isotretinoin exposed pregnancies and adverse fetal and neonatal events
      potentially related to the exposure still occur. These findings from the
      Netherlands add to the evidence that there is no full compliance to the
      isotretinoin PPP in many Western countries. Given the limited success of iPLEDGE,
      the question is which further measures are able to improve compliance.

PMID- 25392023
TI  - Acupuncture for postherpetic neuralgia: a systematic review protocol.
AB  - INTRODUCTION: Postherpetic neuralgia (PHN) is one of the most common
      complications following herpes zoster. Clinical trials indicate that acupuncture
      could reduce pain and discomfort among patients with PHN. This protocol aims to
      describe how to accumulate the current evidence on the efficacy and safety of
      acupuncture for treating PHN. METHODS AND ANALYSIS: This systematic review will
      electronically search multiple databases including the Cochrane Skin Group Trials
      Register, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials
      (CENTRAL), the Chinese Biomedical Literature Database (CBM), the Chinese Medical
      Current Content (CMCC) and the China National Knowledge Infrastructure (CNKI),
      and will hand search a list of medical journals as a supplement. Any clinical
      randomised controlled trials related to acupuncture for treating PHN will be
      included. Outcomes will include pain intensity, global impression, quality of
      life, safety and costs. By screening the titles, abstracts and full texts, two
      reviewers will independently select studies, extract data, and assess study
      quality. Meta-analysis of randomised controlled trials will be conducted using
      Revman 5.1 software. The results will be presented as risk ratio for dichotomous
      data, and standardised or weighted mean difference for continuous data. ETHICS
      AND DISSEMINATION: This systematic review does not need ethical approval because
      there are no data used in our study that are linked to individual patient data.
      Also, the findings will be disseminated through a peer-review publication or
      conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO registration number:
      CRD42014009555.

PMID- 25392025
TI  - [Editorial].

PMID- 25392024
TI  - Using Best-Worst Scaling to Measure Caregiver Preferences for Managing their
      Child's ADHD: A Pilot Study.
AB  - BACKGROUND: Management of attention-deficit/hyperactivity disorder (ADHD) is a
      trade-off between caregivers' concerns about the benefits versus the risks of
      evidence-based treatment. Few studies have used choice-based methods to assess
      what treatment attributes matter most to caregivers. OBJECTIVE: The aim was to
      develop and to pilot an instrument to elicit caregivers' preferences for evidence
      based management of their child's ADHD. METHODS: Mixed methods were used to
      develop a Best-Worst Scaling (BWS) instrument, and quantitative methods were used
      to pilot the instrument. Primary caregivers of children with ADHD from two
      community organizations were recruited for the development (n = 21) and pilot (n
      = 37) phase. The instrument was a BWS case 2, where 18 management profiles are
      presented one at a time, with respondents indicating the one best and one worst
      feature of each profile. Profiles were developed using a main effects orthogonal
      array. The mean of best-minus-worse scores was estimated, and attribute
      importance was based on the sum of maximum minus minimum scores for each
      attribute. Feasibility of eliciting stated preferences was evaluated with t tests
      and 95 % confidence intervals. RESULTS: Seven attributes (medication, therapy,
      school, caregiver training, provider specialty, provider communication, and out
      of-pocket costs) with three levels each were identified. All mean scores were
      significant except for pediatrician management of the child's ADHD (p = 0.089).
      Caregiver training had the highest relative importance, followed by medication
      and provider communication. CONCLUSIONS: The BWS instrument was a relatively
      simple measure, caregivers completed it independently, and it distinguished the
      relative importance of different attributes in managing a child's ADHD.

PMID- 25392026
TI  - [Risk factors for falls in the pediatric setting at the Hospital Agency of United
      Hospitals of Bergamo: a retrospective observational study].
AB  - PURPOSE: To identify the main and most significant risk factors for falls and
      improve the quality of care delivered to pediatric patients by providing
      indications for interventions for the prevention of falls. METHODS: To
      investigate the correlation between falls and risk factors a retrospective
      observational case-control study was carried out, the sample was made up by all
      children who fell from 2004 to 2011 between 0-18 y.o. for which there was a
      record of the fall. RESULTS: 108 children were included in the study (36 cases
      and 72 controls). The data showed that 4 drugs have a correlation with falls,on
      the contrary intravenous therapy seemed to be a factor that protects against the
      risk of falling. CONCLUSION: The study confirms the importance of the problem of
      falls in children. A greater sample size could help to identify additional
      independent variables. This study may represent a starting point for further
      analysis.

PMID- 25392027
TI  - [Non-urgent access to care and nurses' roles in the Emergency Department: a
      narrative literature review].
AB  - PURPOSE: To detect what is written in literature with respect to the access of
      non-urgent patients in Emergency Department, highlighting associated nursing
      roles during the period 2003-2013. METHOD: A literature review on international
      literature was carried out using PubMed database, where 41 significant articles
      were selected. RESULTS: The articles analyzed are focused on the organization of
      the E.D., the response patterns (Fast Track-See and Treat etc.) in some countries
      and the evaluation of the nursing roles and competences. In literature, the model
      and the roles studied have proved to be effective in reducing waiting times in
      E.D. and increasing users' satisfaction without reducing the quality of provided
      care. CONCLUSIONS: The literature shows that the implementation of Fast Track
      must be developed with a nursing staff with advanced skills on emergency. The
      introduction of these roles assumes that health systems should address the
      problem of inter-professional work.

PMID- 25392028
TI  - [Mutuality in caregiving: a literature review].
AB  - INTRODUCTION: Mutuality, understood as a feeling of intimacy and positive
      relationship between caregiver and care receiver, is gaining an increasing
      interest in the scientific arena in the light of socio-demographic change and the
      increase in chronic degenerative diseases. The purpose of this article is to
      carry out a critical analysis of the literature on mutuality in order to identify
      predictors and outcomes. METHOD: A literature search was carried out the
      databases PubMed, CINAHL, PsycInfo, and ASSIA Sociological. Twenty (20) articles
      were selected. By analyzing critically all articles, emerges that mutuality is a
      key variable in the process of care giving and in mental and physical health of
      both caregiver and care-receiver. In the caregiver, high levels of mutuality are
      associated with less stress, depression and burden to a better quality of life
      and self perceived health; in patients high mutuality is able to speed up the
      recovery from the disease, to reduce anxiety and depression and to improve the
      quality of life. CONCLUSION: Future studies aimed at the study of this variable
      also in the Italian population could be of support in developing programs to
      improve quality of life of caregivers and care receiver.

PMID- 25392029
TI  - [Risk of hemolysis in blood sampling from peripheral intravenous catheter: a
      literature review].
AB  - SCOPE: Hemolysis is one of the main factors that can damage a blood sample. The
      availability of an intravenous line already placed pushes many nurses to use this
      route for blood drawing, even if it is known that this technique is associated
      with an increased rate of hemolysis compared to blood sampling with a needle. The
      aim of this work is to identify interventions that reduce risk of hemolysis if
      the blood sample is from a peripheral IV catheter. METHOD: A review of relevant
      literature was conducted through the databases MEDLINE, CINAHL and Cochrane
      database of Systematic Reviews. RESULTS: Fifteen studies were retrieved. Factors
      such as the material and the caliber of the IV catheter, the presence of
      obstructions, the anatomical site, the permanence of the tourniquet, the
      difficulty of positioning of the catheter, the volume of the tube used and the
      skills of the operator are decisive in the risk of hemolysis of the sample. In
      term of cost and preferences of the patient, the technique of blood sampling from
      a peripheral IV catheter is preferable. CONCLUSIONS: Sample collection through
      intravenous catheters is associated with significant higher risk of hemolysis.
      Take a sample of blood from a peripheral catheter to carry out an analysis and,
      at the same time, reduce the risk of hemolysis is possible if some precautions
      are followed.

PMID- 25392030
TI  - [Communication denied: a pilot study on critical relationship in nursing].
AB  - INTRODUCTION: In literature there are few studies on denied nursing
      communication/relationship and why this communication/relationship is avoided.
      GOALS: Evaluate criticism in communication/relationship in nursing in order to
      build an analytical basis for further study. MATERIAL AND METHODS: Participant
      observation during internship placements, diary and notes taken during the
      observation, furthermore the whole work context as well as the relationship in a
      internal medicine department were taken into consideration. RESULTS: In the
      majority of cases communication is avoided, reducing the time of contact with
      patients, in others it is sought even when not expressly required by the patient.
      CONCLUSIONS: Escape relationship may be an indicator of professional insecurity.
      The denied relationship is a mirror in which the practitioner finds its
      weaknesses. Considering these elements promotes the therapeutic path. The study
      gave interesting and relevant insights which can be considered as starting point
      for further research on the field with a wider sample.

PMID- 25392031
TI  - A literature review on self-care of chronic illness: definition, assessment and
      related outcomes.
AB  - INTRODUCTION: Chronic illnesses care represents a challenging issue for people
      well-being and future health systems' sustainability. Promotion of self-care is
      considered a key point for chronically ill patients' care. The aim of this
      literature was to explore: how self-care of chronic illness has been
      theoretically defined; how self-care can be assessed in clinical and research
      settings; what associations exist between self-care and health outcomes of
      chronically ill patients. RESULTS: A wide range of definitions and terminologies
      related to self-care of chronic illness has been found in the literature.
      Although some common elements useful to explain the concept of self-care have
      been identified, the physical, cognitive, emotional and social processes
      underlying self-care remain controversial and poorly defined. Valid and reliable
      disease-specific assessment tools have been developed and used in a growing
      number of studies; however, the lack of utilization of standardized instruments
      in clinical practice has been referred by many authors. Significant correlations
      between self-care of chronic illness and outcome measures e.g. general health
      status, quality of life and healthcare costs, are reported by a limited number of
      studies. CONCLUSION: Supporting patient self-care is recognized as a crucial
      factor in chronic illness care. A deeper analysis of variables and processes
      influencing self-care could help for a full description of the phenomenon. A
      systematic evaluation of self-care in health professionals' everyday clinical
      practice is strongly recommended. The development of general non-disease-specific
      assessment tools could facilitate the evaluation of complex patients, especially
      those with multiple co-morbidities. Although self-care has been recognized as a
      vital intermediate outcome, further large-scale studies clarifying the
      association between self-care and patients' and health systems' outcomes are
      needed.

PMID- 25392032
TI  - Three cases of laparoscopic total gastrectomy with intracorporeal
      esophagojejunostomy for gastric cancer in remnant stomach.
AB  - Gastric cancer in remnant stomach is a rare tumor but with poor prognosis.
      Compared with conventional open surgery, laparoscopic gastrectomy has potential
      benefits for these patients due to advantages resulting from its minimally
      invasive approach. Herein, we report on three patients with gastric cancer in
      remnant stomach who underwent laparoscopic total gastrectomy with intracorporeal
      esophagojejunostomy successfully. The operative time was 280, 250 and 225
      minutes, the estimated blood loss was 100, 80 and 50 ml and the length of
      postoperative hospital stay was seven, eight and nine days respectively. Our
      experience has suggested that laparoscopic total gastrectomy with intracorporeal
      esophagojejunostomy can be a safe, feasible and promising option for patients
      with gastric cancer in remnant stomach. 

PMID- 25392033
TI  - Acoustic rainbow trapping by coiling up space.
AB  - We numerically realize the acoustic rainbow trapping effect by tapping an air
      waveguide with space-coiling metamaterials. Due to the high refractive-index of
      the space-coiling metamaterials, our device is more compact compared to the
      reported trapped-rainbow devices. A numerical model utilizing effective
      parameters is also calculated, whose results are consistent well with the direct
      numerical simulation of space-coiling structure. Moreover, such device with the
      capability of dropping different frequency components of a broadband incident
      temporal acoustic signal into different channels can function as an acoustic
      wavelength division de-multiplexer. These results may have potential applications
      in acoustic device design such as an acoustic filter and an artificial cochlea. 

PMID- 25392036
TI  - Waves...from the inside.

PMID- 25392035
TI  - Cold fluids during cardiac arrest: faster cooling but not better outcome!

PMID- 25392037
TI  - Chytridiomycosis risk among Central European amphibians based on surveillance
      data.
AB  - The Czech Republic hosts a surprisingly rich biodiversity of amphibians
      representing the majority of amphibian species present in all of Central and
      Eastern Europe. Surveillance data of Batrachochytrium dendrobatidis (Bd)
      collected during 2008 to 2012 were analysed for basic patterns of prevalence and
      infection intensity among species, age groups and localities. In addition, an
      investigation was made into possible data bias due to varying PCR inhibition.
      Infection prevalence in the genus Pelophylax was significantly higher than in
      other sampled taxa, while Bombina and Bufo were infected with intermediate
      prevalence. Individual mortalities putatively caused by chytridiomycosis were
      detected in Bombina and Bufo, but not in Pelophylax. Differences among localities
      were seen to modulate the pathogen's infection rate and influence overall
      individual infection intensities. PCR inhibition occurred significantly more
      often in samples from the genus Pelophylax than in other tested taxa (Bufo bufo,
      B. viridis, Bombina bombina, Pelobates fuscus and Rana dalmatina). Although we
      found no completely inhibited samples within the genus Bombina, the infection
      loads were lower in the sample set processed without bovine serum albumin,
      suggesting some level of PCR inhibition. The combination of high Bd prevalence
      with no apparent deleterious effect and the high dispersal abilities of water
      frogs predispose them to act as vectors for chytridiomycosis. It is possible that
      the role of Pelophylax frogs in the spread of Bd is overlooked due to a large
      proportion of unrecognized false negatives, but this issue needs further
      confirmation. 

PMID- 25392034
TI  - Consensus on circulatory shock and hemodynamic monitoring. Task force of the
      European Society of Intensive Care Medicine.
AB  - OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in
      multiorgan failure and a high mortality rate. The aim of this consensus is to
      provide support to the bedside clinician regarding the diagnosis, management and
      monitoring of shock. METHODS: The European Society of Intensive Care Medicine
      invited 12 experts to form a Task Force to update a previous consensus (Antonelli
      et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed
      in the earlier consensus were used as the outline for the literature search and
      review, with the aim of the Task Force to produce statements based on the
      available literature and evidence. These questions were: (1) What are the
      epidemiologic and pathophysiologic features of shock in the intensive care unit?
      (2) Should we monitor preload and fluid responsiveness in shock? (3) How and when
      should we monitor stroke volume or cardiac output in shock? (4) What markers of
      the regional and microcirculation can be monitored, and how can cellular function
      be assessed in shock? (5) What is the evidence for using hemodynamic monitoring
      to direct therapy in shock? Four types of statements were used: definition,
      recommendation, best practice and statement of fact. RESULTS: Forty-four
      statements were made. The main new statements include: (1) statements on
      individualizing blood pressure targets; (2) statements on the assessment and
      prediction of fluid responsiveness; (3) statements on the use of echocardiography
      and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements
      that can be used at the bedside to diagnose, treat and monitor patients with
      shock.

PMID- 25392038
TI  - High susceptibility of the endangered dusky gopher frog to ranavirus.
AB  - Amphibians are one of the most imperiled vertebrate groups, with pathogens
      playing a role in the decline of some species. Rare species are particularly
      vulnerable to extinction because populations are often isolated and exist at low
      abundance. The potential impact of pathogens on rare amphibian species has seldom
      been investigated. The dusky gopher frog Lithobates sevosus is one of the most
      endangered amphibian species in North America, with 100-200 individuals remaining
      in the wild. Our goal was to determine whether adult L. sevosus were susceptible
      to ranavirus, a pathogen responsible for amphibian die-offs worldwide. We tested
      the relative susceptibility of adult L. sevosus to ranavirus (103 plaque-forming
      units) isolated from a morbid bullfrog via 3 routes of exposure: intra-coelomic
      (IC) injection, oral (OR) inoculation, and water bath (WB) exposure. We observed
      100% mortality of adult L. sevosus in the IC and WB treatments after 10 and 19 d,
      respectively. Ninety-five percent mortality occurred in the OR treatment over the
      28 d evaluation period. No mortality was observed in the control treatment after
      28 d. Our results indicate that L. sevosus is susceptible to ranavirus, and if
      adults in the wild are exposed to this pathogen, significant mortality could
      occur. Additionally, our study demonstrates that some adult amphibian species can
      be very susceptible to ranavirus, which has been often overlooked in North
      American studies. We recommend that conservation planners consider testing the
      susceptibility of rare amphibian species to ranavirus and that the adult age
      class is included in future challenge experiments. 

PMID- 25392039
TI  - Differential susceptibility in steelhead trout populations to an emergent MD
      strain of infectious hematopoietic necrosis virus.
AB  - A significant emergence of trout-adapted MD subgroup infectious hematopoietic
      necrosis virus (IHNV) began in the coastal region of Washington State, USA, in
      2007. This emergence event lasted until 2011 and caused both asymptomatic adult
      fish infection and symptomatic epidemic disease and mortality in juvenile fish.
      Incidence of virus during this emergence demonstrated a heterogeneous
      distribution among rivers of the coastal region, leaving fish populations of some
      rivers apparently untouched while others suffered significant and recurrent
      infection and mortality (Breyta et. al. 2013; Dis Aquat Org 104:179-195). In this
      study, we examined the possible contribution of variations in susceptibility of
      fish populations, age-related resistance, and virus virulence to the observed
      landscape heterogeneity. We found that the most significant variable was host
      susceptibility: by controlled experimental challenge studies steelhead trout
      populations with no history of IHNV infection were 1 to 3 orders of magnitude
      more sensitive than a fish population with a long history of IHNV infection. In
      addition, 2 fish populations from the same river, which descended relatively
      recently from a common ancestral population, demonstrated 1 to 2 orders of
      magnitude difference in susceptibility. Fish age-related development of
      resistance was most evident in the more susceptible of 2 related fish
      populations. Finally, the strain of virus involved in the 2007 coastal Washington
      emergence had high virulence but was within the range of other known M group
      viruses tested. These results suggest that one major driver of landscape
      heterogeneity in the 2007 coastal Washington IHNV emergence was variation in fish
      population susceptibility and that this trait may have a heritable component. 

PMID- 25392040
TI  - Detection of koi herpesvirus (KHV) in healthy cyprinid seed stock.
AB  - Koi herpesvirus (KHV) disease is a lethal disease in common carp, an important
      food fish in Asian countries, the seed of which is used in restocking programs
      for freshwater fishery management. We inspected apparently healthy seed stock of
      common carp Cyprinus carpio L. and Siberian crucian carp Carassius auratus for
      the presence of KHV using PCR-based diagnostic tests as a part of a stock
      enhancement program from 2009 to 2010 in Korea. Consequently, KHV was detected
      from 24 of 232 inspections with yearly detection percentages of 5.2% in 2009 and
      15.5% in 2010 using PCR primer sets for TK or SphI-5 as recommended by the OIE
      Manual of Diagnostic Tests for Aquatic Animals. Results indicate that the SphI-5
      primer set was slightly more sensitive than the TK primer set, as shown by a
      higher detection rate. To determine the genotype of the KHV strains detected in
      this study, ORF40-specific PCR amplification was conducted, and the PCR products
      from 6 samples showed 100% nucleotide sequence identity with a Japanese strain
      (GenBank accession number AP008984) but not with US (DG657948) and Israeli
      strains (DG177346). This report conclusively demonstrated the presence of KHV in
      externally healthy seed of common carp and Siberian crucian carp, indicating a
      possible risk that subclinically infected seed stock can be released with a
      potential threat to wild populations. 

PMID- 25392041
TI  - Detection and application of circular (concatemeric) DNA as an indicator of koi
      herpesvirus infection.
AB  - Herpesviruses form a long continuous DNA molecule, or head-to-tail concatemer, as
      a replicating intermediate in the host. In this study, we developed a DNA
      specific PCR assay for detecting the infection stage of koi herpesvirus (KHV)
      based on the presence of this 'endless' DNA. The 295 kbp double-stranded DNA KHV
      genome consists of a 251 kbp unique long region and two 22 kbp direct repeats
      (DRL and DRR) at each genome terminus. We designed a new primer set (DR primer
      set) based on the DR region spanning the presumed circular or concatemeric
      junction. Using the DR primer set, a PCR product was obtained from KHV-infected
      common carp brain (CCB) cells, but not from the virus-infected cell culture
      supernatant, implying that the PCR assay could detect intracellular virus in the
      host. The synthesis of a presumptive circular or concatemeric genome in virus
      infected CCB cells was examined in a time-course experiment together with viral
      mRNA of the terminase gene, copy numbers of the viral genome, and infectious
      viral titer. The mRNA was first detected in the cells at 6 h post-inoculation
      (hpi), and the copy number of viral genome in the cells started to increase at 12
      hpi. Subsequently, circular or concatemeric DNA was detected in the cells at 18
      hpi, and progeny virus was detected in the cell culture supernatant at 24 hpi.
      These findings suggest that detection of the circular or concatemeric KHV genome
      with the developed PCR method can be used to determine the stage of KHV
      infection. 

PMID- 25392042
TI  - Deciphering the biodiversity of fish-pathogenic Flavobacterium spp. recovered
      from the Great Lakes basin.
AB  - Flavobacterial diseases negatively impact wild and cultured fishes worldwide. We
      recently reported on the presence of a large and diverse group of flavobacteria,
      many of which were associated with lesions in a number of Great Lakes fish
      species. Herein, we report on the characterization of 65 fish-associated
      Flavobacterium spp. isolates using 16S rRNA gene sequence analysis and
      phylogenetic analyses based upon neighbor-joining and Bayesian methodologies.
      Thirteen isolates were identified as the newly described fish-associated F.
      plurextorum, F. spartansii, and F. tructae, while 3 isolates were similar to F.
      frigidimaris; however, the remaining Flavobacterium spp. isolates did not
      conclusively match any described Flavobacterium spp. and thus were suspected as
      comprising novel flavobacterial species. A more comprehensive polyphasic
      characterization was undertaken on 6 isolates, representing a range of
      association with disease signs in hatchery-raised or free-ranging fish and
      genetic distinctness. Polyphasic characterization included physiological,
      morphological, and biochemical analyses, as well as additional phylogenetic
      analyses based upon near-complete sequencing of the 16S rRNA gene. Our findings
      demonstrated that that at least 5 of the 6 isolates are most likely novel species
      within the genus Flavobacterium that have never before been reported from fish.
      Pilot experimental challenge studies suggested that some of these Flavobacterium
      spp. can cause pathological lesions in fish and were re-isolated from the brains,
      spleens, livers, and kidneys of experimentally infected fish. The findings
      underscore the growing number and heterogeneity of flavobacteria now known to be
      capable of infecting fish. 

PMID- 25392043
TI  - Pathology of Haplosporidium patagon affecting siphonariid gastropods in
      Patagonia.
AB  - Haplosporidium patagon was found parasitizing Siphonaria lessonii and S.
      lateralis, 2 siphonariid gastropods co-occurring on the littoral rocky shore at
      Puerto Deseado, Santa Cruz, Argentina. Gastropods from 2 habitats representing 2
      different levels of environmental harshness were studied. In both cases, S.
      lessonii showed a higher prevalence of infection (3.78%) over the entire 14 mo
      study period than S. lateralis (0.13%). Very different values of prevalence of
      infection were observed at the different sampling sites: Site 1, the more
      restrictive habitat (exposed for long periods to desiccation during low tides,
      higher ultraviolet exposure, and high ranges of temperature variation) showed a
      higher prevalence value (5.99%) than Site 2 (1.46%). Statistical differences in
      prevalence were also found between values corresponding to the austral spring
      (3.35% at Site 1 and 0.74% at Site 2) and winter (13.79% at Site 1 and 2.13% at
      Site 2). The presence/absence of H. patagon did not vary significantly with
      gastropod shell length. Infection affected the digestive gland, whose normal
      histology was greatly modified. The hermaphroditic gonads were also affected; the
      female germinal cells disappeared or only a few primary or previtellogenic
      oocytes were present, and vitellogenesis was inhibited. The function of the male
      germinal epithelium, as well as spermatogenesis and spermiogenesis processes and
      associated organs (seminal vesicles and seminal receptacles), were not affected.
      However, the glandular pallial complex of the reproductive systemwas affected,
      and we observed a significant reduction in development in parasitized gastropods.
      H. patagon sporocysts also invaded the supporting connective tissues of both the
      kidney and pseudobranch. 

PMID- 25392044
TI  - New data on Perkinsus mediterraneus in the Balearic Archipelago: locations and
      affected species.
AB  - Perkinsus mediterraneus, a protozoan parasite that can cause perkinsosis (marine
      mollusc disease), was first detected in oysters Ostrea edulis from Mahon
      (Minorca, Balearic Islands, Spain) in 2004. Several years later it was also found
      in Andratx Harbour (Majorca, Balearic Islands) and in the Gulf of Manfredonia
      (Adriatic coast of Italy) in oyster populations. Since 2007, Perkinsus surveys
      have been conducted in different localities and shellfish species in the Balearic
      Archipelago. In the present work, we found P. mediterraneus in the Balearic
      Islands infecting oyster and other shellfish species. We describe infection with
      P. mediterraneus for the first time in Arca noae and Mimachlamys varia. The
      detection was carried out using Ray's fluid thioglycolate medium (RFTM),
      histology and polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) methodologies. The internal transcribed spacer (ITS) region (including
      ITS1, 5.8S and ITS2) of P. mediterraneus ribosomal DNA was sequenced from
      infected bivalve gills (or from the body in Chamelea gallina) from Balearic
      Archipelago localities. Twelve haplotypes with a strong genetic similarity
      between them (97-100%) were observed in our samples. These data were completed
      with 12 more haplotypes from GenBank sequences. The phylogenetic relationship
      between Balearic P. mediterraneus haplotypes found in this study, those
      previously obtained in Mahon Harbour, and the Perkinsus spp. sequences available
      in GenBank clearly grouped the different Perkinsus spp. in distinct clades
      supported by strong bootstrap values. Moreover, these analyses detected different
      P. mediterraneus groups in O. edulis from Minorca Island. No abnormal mortalities
      or decline in populations were detected during the survey, except for C. gallina,
      which is also affected by Marteilia refringens. 

PMID- 25392045
TI  - Pathogenic fungus Batrachochytrium dendrobatidis in marbled water frog
      Telmatobius marmoratus: first record from Lake Titicaca, Bolivia.
AB  - The pathogenic fungus Batrachochytrium dendrobatidis (Bd) has been associated
      with amphibian declines worldwide but has not been well-studied among Critically
      Endangered amphibian species in Bolivia. We sampled free-living marbled water
      frogs Telmatobius marmoratus (Anura: Leptodactylidae) from Isla del Sol, Bolivia,
      for Bd using skin swabs and quantitative polymerase chain reactions. We detected
      Bd on 44% of T. marmoratus sampled. This is the first record of Bd in amphibians
      from waters associated with Lake Titicaca, Bolivia. These results further confirm
      the presence of Bd in Bolivia and substantiate the potential threat of this
      pathogen to the Critically Endangered, sympatric Titicaca water frog T. culeus
      and other Andean amphibians. 

PMID- 25392046
TI  - Infectious Keratitis Following Corneal Crosslinking: A Systematic Review of
      Reported Cases: Management, Visual Outcome, and Treatment Proposed.
AB  - AIM: To describe the infectious complications and the group of pathogens involved
      in the infection following corneal crosslinking, the visual outcome, and the
      treatment proposed. METHODS: A Medline (National Library of Medicine, Bethesda,
      MD, USA) search from October 2000 to October 2013 was performed to identify all
      articles describing infectious keratitis following corneal crosslinking
      treatment. Nineteen articles were selected. Ten articles reported infectious
      complications of corneal crosslinking treatment were included. Nine articles were
      excluded, because seven described sterile keratitis, one article was in German,
      and one reported general complication without describing the infection
      complication. RESULTS: A total number of infections reported included 10 eyes.
      The infectious keratitis was associated with bacteria in five eyes (50%): gram
      positive bacteria in three eyes (30%) (staphylococcus epidermidis, S. aureus and
      streptococcus salivarius plus S. oralis, respectively) and gram-negative bacteria
      in two eyes (20%) (E. coli; P. aeruginosa); there was herpes virus in two eyes,
      fungus in two eyes (Fusarium and Microsporidia) (20%), and Acanthamoeba in one
      eye (10%). CONCLUSIONS: Only 10 cases of infectious keratitis following corneal
      crosslinking are published. The most virulent pathogens were Pseudomonas
      aeruginosa and Acanthamoeba. Less virulent organisms were Escherichia coli and S.
      epidermidis. Two cases of herpes keratitis were described, suggesting the
      possibility of systemic antiviral prophylaxis before corneal crosslinking
      treatment. The most common risk factor of infections identified was postoperative
      incorrect patient behavior.

PMID- 25392047
TI  - Thromboelastography in off-pump coronary artery bypass grafting.
AB  - BACKGROUND: Thromboelastography enables complete evaluation of the process of
      clot initiation, the structural characteristics of the formed clot and its
      stability. Many previous studies have assessed the predictive role of
      thromboelastography in on-pump cardiac surgery, but there are no clear guidelines
      on its use in off-pump coronary artery bypass. The aim of this study was to
      evaluate the use of thromboelastography and its relevance during the
      postoperative period following off-pump coronary artery bypass. METHODS: This was
      a one-year prospective study on 55 patients undergoing off-pump coronary artery
      bypass for coronary artery disease. Thromboelastography was performed as a
      bedside investigation in the cardiothoracic and vascular surgery intensive care
      unit. RESULTS: The association between maximum amplitude and total blood loss
      <500 mL compared to blood loss >500 mL was statistically significant (p < 0.001).
      Using receiver operator characteristic curve analysis, it was seen that with
      increasing maximum amplitude values, a decrease in blood loss was observed. A
      cutoff value of maximum amplitude <49.63 mm was regressed to have a predicted
      sensitivity of 100% and a predicted specificity of 89.3% for prediction of blood
      loss >500 mL. CONCLUSIONS: Thromboelastographic parameters show a reliable
      correlation with increased blood loss in off-pump coronary artery bypass
      grafting, and predict patients with an increased chance of blood requirement as
      well as those at risk of a hypercoagulable state.

PMID- 25392048
TI  - Bioprosthetic mitral valve dysfunction due to native valve preserving procedure.
AB  - Mitral valve replacement with preservation of the mitral leaflets and subvalvular
      apparatus is considered to maintain left ventricular geometry and function and
      reduce the risk of myocardial rupture. However, the routine use of this technique
      may lead to early complications such as left ventricular outflow tract
      obstruction and even mitral inflow obstruction, requiring reoperation. We
      describe a rare case of bioprosthetic mitral valve dysfunction caused by a native
      valve preserving procedure. 

PMID- 25392049
TI  - The surgical management of a giant pleomorphic liposarcoma of the chest wall.
AB  - Pleomorphic liposarcomas are rare entities with less than 40 cases diagnosed each
      year, of which a small proportion arise from the chest wall. Optimal management
      involves wide local resection with negative margins. We describe the case of a 69
      year-old gentleman with a chronically growing chest wall mass. After computed
      tomography and positron-emission tomography, the mass was resected. Chest wall
      reconstruction was performed with mesh and a transverse rectus abdominis
      myocutaneous flap. The patient did well postoperatively, with no evidence of
      recurrence at 10 months. 

PMID- 25392050
TI  - Robust Generation of Cardiomyocytes from Human iPS Cells Requires Precise
      Modulation of BMP and WNT Signaling.
AB  - Various strategies have been published enabling cardiomyocyte differentiation of
      human induced pluripotent stem (iPS) cells. However the complex nature of
      signaling pathways involved as well as line-to-line variability compromises the
      application of a particular protocol to robustly obtain cardiomyocytes from
      multiple iPS lines. Hence it is necessary to identify optimized protocols with
      alternative combinations of specific growth factors and small molecules to
      enhance the robustness of cardiac differentiation. Here we focus on systematic
      modulation of BMP and WNT signaling to enhance cardiac differentiation. Moreover,
      we improve the efficacy of cardiac differentiation by enrichment via lactate.
      Using our protocol we show efficient derivation of cardiomyocytes from multiple
      human iPS lines. In particular we demonstrate cardiomyocyte differentiation
      within 15 days with an efficiency of up to 95 % as judged by flow cytometry
      staining against cardiac troponin T. Cardiomyocytes derived were functionally
      validated by alpha-actinin staining, transmission electron microscopy as well as
      electrophysiological analysis. We expect our protocol to provide a robust basis
      for scale-up production of functional iPS cell-derived cardiomyocytes that can be
      used for cell replacement therapy and disease modeling.

PMID- 25392051
TI  - Ebola hemorrhagic fever: current outbreak and progress in finding a cure.

PMID- 25392052
TI  - Long-range electron transfer triggers mechanistic differences between iron(IV)
      oxo and iron(IV)-imido oxidants.
AB  - Nature often utilizes molecular oxygen for oxidation reactions through
      monoxygenases and dioxygenases. In many of these systems, a high-valent iron(IV)
      oxo active species is found. In recent years, evidence has accumulated of
      possible iron(IV)-imido and iron(V)-nitrido intermediates in enzymatic catalysis,
      although little is known about their activity. In this work, we report a detailed
      combined kinetics and computational study on the difference in reactivity and
      chemical properties of nonheme iron(IV)-oxo compared with iron(IV)-tosylimido. We
      show here that iron(IV)-tosylimido complex is much more reactive with sulfides
      than the corresponding iron(IV)-oxo complex; however, the reverse trend is
      obtained for hydrogen atom abstraction reactions. The latter proceed with a
      relatively small kinetic isotope effect of kH/kD = 7 for the iron(IV)-tosylimido
      complex. Moreover, a Hammett analysis of hydrogen atom abstraction from para-X
      benzyl alcohol reveals a slope of close to zero for the iron(IV)-oxo, whereas a
      strong negative slope is found for the iron(IV)-tosylimido complex. These studies
      implicate dramatic changes in the reaction mechanisms and suggest a considerable
      charge transfer in the transition states. Density functional theory calculations
      were performed to support the experiments and confirm an initial long-range
      electron transfer for the iron(IV)-tosylimido complex with substrates, due to a
      substantially larger electron affinity compared with the iron(IV)-oxo species. As
      a consequence, it also reacts more efficiently in electrophilic addition
      reactions such as those with sulfides. By contrast, the long-range electron
      transfer for the iron(IV)-tosylimido complex results in a rate constant that is
      dependent on the pi*xz -> sigma*z(2) excitation energy, which raises the hydrogen
      atom abstraction barrier above that found for the iron(IV)-oxo. On the other
      hand, sulfimidation has much earlier electron transfer steps with respect to
      sulfoxidation. All data has been analyzed and rationalized with valence bond
      models and thermochemical cycles. Our studies highlight the catalytic potential
      of iron(IV)-tosylimido complexes in chemistry and biology. 

PMID- 25392053
TI  - Popular epidemiology and "fracking": citizens' concerns regarding the economic,
      environmental, health and social impacts of unconventional natural gas drilling
      operations.
AB  - Pennsylvania sits atop the Marcellus Shale, a reservoir of natural gas that was
      untapped until the 2004 introduction of unconventional natural gas drilling
      operations (UNGDO) in the state. Colloquially known as fracking, UNGDO is a
      controversial process that employs large volumes of water to fracture the shale
      and capture gas; it has become a multi-billion dollar industry in Pennsylvania.
      We analyzed letters to the editor of the most widely circulated local newspaper
      in the most heavily drilled county in Pennsylvania (Bradford County) in order to
      characterize residents' concerns and their involvement in popular epidemiology-
      the process by which citizens investigate risks associated with a perceived
      environmental threat. We reviewed 215 letters to the editor that referenced
      natural gas operations and were published by The Daily Review between January 1,
      2008 and June 8, 2013. We used NVivo 10 to code and analyze letters and identify
      major themes. Nvivo is qualitative data analysis software
      (http://www.qsrinternational.com/products_nvivo.aspx) that allows researchers to
      code and analyze "unstructured" data, including text files of any type (e.g.,
      interview transcripts, news articles, letters, archival materials) as well as
      photographs and videos. Nvivo can be used to classify, sort, query, comment on,
      and share data across a research group. Letters demonstrated citizen engagement
      in beginning and intermediate stages of lay epidemiology, as well as discord and
      stress regarding four main issues: socio-economic impacts, perceived threats to
      water, population growth and implications, and changes to the rural landscape.
      Residents called for stronger scientific evidence and a balance of economic
      development and health and environmental protections. Citizens' distress
      regarding UNGDO appeared to be exacerbated by a dearth of information to guide
      economic growth and health, environmental, and social concerns. This analysis
      proposes locally informed questions to guide future surveillance and research.

PMID- 25392054
TI  - Mitral valve analysis using a novel 3D holographic display: a feasibility study
      of 3D ultrasound data converted to a holographic screen.
AB  - The aim of the present study was to test the feasibility of analyzing 3D
      ultrasound data on a novel holographic display. An increasing number of mini
      invasive procedures for mitral valve repair require more effective visualization
      to improve patient safety and speed of procedures. A novel 3D holographic display
      has been developed and may have the potential to guide interventional cardiac
      procedures in the near future. Forty patients with degenerative mitral valve
      disease were analyzed. All had complete 2D transthoracic (TTE) and
      transoesophageal (TEE) echocardiographic examinations. In addition, 3D TTE of the
      mitral valve was obtained and recordings were converted from the echo machine to
      the holographic screen. Visual inspection of the mitral valve during surgery or
      TEE served as the gold standard. 240 segments were analyzed by 2 independent
      observers. A total of 53 segments were prolapsing. The majority included P2 (31),
      the remaining located at A2 (8), A3 (6), P3 (5), P1 (2) and A1 (1). The
      sensitivity and specificity of the 3D display was 87 and 99 %, respectively
      (observer I), and for observer II 85 and 97 %, respectively. The accuracies and
      precisions were 96.7 and 97.9 %, respectively, (observer I), 94.3 and 88.2 %
      (observer II), and inter-observer agreement was 0.954 with Cohen's Kappa 0.86. We
      were able to convert 3D ultrasound data to the holographic display. A very high
      accuracy and precision was shown, demonstrating the feasibility of analyzing 3D
      echo of the mitral valve on the holographic screen.

PMID- 25392056
TI  - New awareness, new populations, new technologies, and new ideas.

PMID- 25392055
TI  - Effects of cardiac resynchronization therapy on left ventricular remodeling and
      dyssynchrony in patients with left ventricular noncompaction and heart failure.
AB  - Left ventricular noncompaction (LVNC) is a rare cardiomyopathy with high
      incidence of heart failure (HF). It is unclear whether LVNC patients with
      desynchronized HF would benefit from cardiac resynchronization therapy (CRT). In
      order to evaluate the effect of CRT on LVNC, this study explored left ventricular
      (LV) remodeling and mechanical synchronicity before and after CRT in LVNC
      patients, and compare with that in idiopathic dilated cardiomyopathy (DCM)
      patients. We collected 15 LVNC and 30 matched DCM patients. All the patients
      underwent clinical evaluation,electrocardiogram and echocardiography before CRT
      and >=6 months later. LV response was defined as >=15 % decrease in LV end
      systolic volume (LVESV). Longitudinal synchronicity was quantified by YU-index
      using tissue Doppler imaging. The time delay of peak radial strain from
      anteroseptal to posterior wall, which derived from speckle tracking imaging, was
      used to quantify radial synchronicity. In LVNC group, LV ejection fraction
      increased from 27.6 +/- 5.5 to 39.1 +/- 7.0 % (P < 0.01) during follow-up, but LV
      volumes did not change significantly (both P > 0.05). Five LVNC patients (33.3 %)
      responded to CRT, and all of them were super-responders (reduction in LVESV > 30
      %). In addition, the number of noncompacted segments and the thickness ratio of
      noncompacted to compacted myocardium decreased (both P < 0.05). Inter
      ventricular, longitudinal and radial intra-ventricular dyssynchrony also reduced
      significantly (all P < 0.05). Compared with DCM group, there was no significant
      difference in LV response rate (33.3 vs. 60.0 %, P = 0.092), improvement of LV
      function and dyssynchrony index (all P < 0.05). In conclusion, CRT improved heart
      function, morphology and mechanical dyssynchrony in LVNC patients.

PMID- 25392057
TI  - Polysubstance use, social anxiety, and length of treatment for alcohol use
      disorders.
AB  - OBJECTIVE: The purpose of the present study was to examine the interactive
      effects of social anxiety and psychosocial factors (i.e., group attendance,
      polysubstance use) on substance use treatment for men with a primary diagnosis of
      alcohol use disorder. Social anxiety and alcohol use disorders often co-occur,
      but it is currently unclear how having high social anxiety might affect aspects
      of substance use treatment, such as group participation and length of stay.
      METHODS: This study compared men with alcohol use disorder only versus those with
      alcohol plus other drug disorders in a residential treatment facility. Measures
      included demographics, self-reported social anxiety, self-reported drug history,
      attendance at treatment groups, and total number of days in treatment. RESULTS:
      Of 128 participants, 39 (30.5%) used only alcohol, while 89 (69.5%) used alcohol
      and other substances. Hierarchical linear regression showed only one significant
      interaction with social anxiety and length of treatment: people who used alcohol
      only or alcohol in addition to other substances (p < .05). Simple effects
      analyses revealed a positive relationship between social anxiety and length of
      stay among men who used only alcohol, but not among men who used more than one
      substance. CONCLUSIONS: Currently, the distinction between those who use only
      alcohol and those who use other substances as well is not often examined in the
      literature. However, the present study shows that this assumption of homogeneity
      may be inaccurate, given the differential relationships that these groups may
      have with factors such as social anxiety.

PMID- 25392058
TI  - Smoking cessation outcomes and predictors among individuals with co-occurring
      substance use and/or psychiatric disorders.
AB  - OBJECTIVE: Individuals with substance use and psychiatric disorders have a high
      prevalence of tobacco use disorders and are disproportionately affected by
      tobacco-related morbidity and mortality. However, it is unclear how having co
      occurring disorders affects tobacco cessation. Our aim was to examine smoking
      cessation outcomes and relevant predictors of smoking cessation among smokers
      with substance use and/or psychiatric disorders. METHODS: Data from medical
      records of 674 participants in a tobacco treatment program within mental health
      and addictions services in Vancouver, Canada, were analyzed. The 26-week
      treatment program included an 8-week structured behavioral counseling group, an
      18-week support group, and 26 weeks of no-cost pharmacotherapy. Information on
      demographics, tobacco use and history, type of pharmacotherapy received, nicotine
      dependence, importance of and confidence in quitting smoking, expired carbon
      monoxide level, substance use and psychiatric disorder history, and total program
      visits were gathered. RESULTS: Approximately 67% (n = 449) of participants had co
      occurring substance use and psychiatric disorders, while 20% (n = 136) had
      substance use disorder only, 10% (n = 67) had psychiatric disorder only, and 3%
      (n = 22) had tobacco dependence only. Rates of tobacco cessation (i.e., 7-day
      point prevalence of abstinence verified by expired carbon monoxide of <=8 ppm) by
      group in the 522 people who completed treatment were as follows: 38.2% for those
      with co-occurring disorders, 47.1% for those with tobacco dependence only, 47.1%
      for those with substance use disorder only, and 41.8% for those with psychiatric
      disorder only. Length of treatment was a significant predictor of smoking
      cessation for those with co-occurring disorders and substance use disorder only.
      In the final stratified multivariate analysis, for individuals with co-occurring
      disorders, having an opiate use disorder (as compared to an alcohol use disorder)
      and higher nicotine dependence scores at baseline were predictive of poor
      cessation outcomes, while greater length of treatment was predictive of
      successful smoking cessation. CONCLUSIONS: Tobacco cessation treatment for
      individuals with co-occurring substance use and psychiatric disorders is likely
      to be as effective as for smokers with either disorder alone. Treatment duration
      predicts success among these smokers so strategies to enhance engagement and
      retention are needed.

PMID- 25392059
TI  - mHealth for dual diagnosis: considering long-term implementation.

PMID- 25392060
TI  - Stimulant medication for ADHD in opioid maintenance treatment.
AB  - OBJECTIVE: The use of central stimulant medication in adults with attention
      deficit hyperactivity disorder (ADHD) who receive opioid maintenance treatment
      remains controversial and empirical evidence is limited. Because of the abuse
      potential of stimulant drugs, Norway has restrictions on prescribing central
      stimulants to individuals who have substance use disorders or who are on opioid
      maintenance treatment. In this naturalistic study, we describe experiences from a
      program through which central stimulant medication was administered to patients
      with ADHD receiving opioid maintenance treatment. METHODS: This report is based
      on a program evaluation of a combined treatment project designed to provide
      stimulant medication to patients with adult ADHD who were receiving opioid
      maintenance treatment. As part of the clinical treatment, patients were monitored
      closely for any medical issues or adverse medication reactions and provided
      regular urine samples for analysis and information regarding demographics,
      treatment goals, legal involvement, diagnoses, substance abuse, and ADHD
      symptoms. Monitoring occurred at baseline, at 2 months (after patients being
      stabilized on the central stimulant), and again at 3, 6 and 24 months. RESULTS:
      Among 42 patients initially offered the combined treatment, 24 were actually
      eligible, 20 started the combined treatment, and 10 stayed in the program. We
      were not able to identify a single major cause of treatment dropout. Patients
      reported significantly fewer symptoms of ADHD at the 6- to 8-week point,
      regardless of whether the data were analyzed using an intent-to-treat (all
      participants) or per-protocol (only those with complete data at all points)
      method. Even though self-assessed ADHD scores dropped significantly during
      treatment, the scores still remained fairly high, suggesting persistent
      functional impairment. Neither severe complications nor increase in substance
      abuse were observed during treatment with central stimulants. CONCLUSIONS: These
      findings show some promise with regard to the safety and utility of central
      stimulant medications for patients with ADHD who are receiving opioid maintenance
      treatment. Our study has methodological limitations, and systematic, well
      designed clinical investigations are needed to increase the knowledge base.

PMID- 25392061
TI  - Predictors and moderators of aftercare appointment-keeping following brief
      motivational interviewing among patients with psychiatric disorders or dual
      diagnosis.
AB  - OBJECTIVE: Non-adherence to psychiatric and substance abuse treatment
      recommendations, especially with regard to aftercare outpatient appointment
      keeping following hospitalizations, exacts a high cost on mental health spending
      and prevents patients from receiving therapeutic doses of treatment. Our primary
      objective was to evaluate the relationship between potential predictors and
      moderators of aftercare appointment-keeping among a group of adult patients
      immediately following hospitalization for severe psychiatric disorders or dual
      diagnosis. METHODS: Candidate predictors and moderator variables included
      demographics, psychiatric status, psychiatric symptom severity, and inpatient
      group adherence, while aftercare appointment-keeping was defined as attendance at
      the first aftercare appointment. Participants were 121 adult inpatients with a
      psychiatric disorder or dual diagnosis originally enrolled in an earlier
      randomized controlled trial comparing standard treatment with standard treatment
      plus brief motivational interviewing for increasing adherence. RESULTS: RESULTS
      indicated that, across treatment conditions, those who were female, did not have
      dual diagnosis, were older (older than 33 years), and were less educated (<high
      school) attended their first aftercare appointment at significantly higher rates
      than their counterparts. A treatment-by-gender interaction was noted, where only
      men were significantly more likely to keep their first aftercare appointment if
      they received standard treatment plus brief motivational interviewing, compared
      to standard treatment alone (OR = 9.58, p < .001). CONCLUSIONS: Findings suggest
      that gender, dual diagnosis status, age and education may be an important
      predictors of aftercare treatment adherence and that gender may be a moderator of
      motivational interviewing among individuals with psychiatric disorders or dual
      diagnosis.

PMID- 25392062
TI  - Opiate dependence in schizophrenia: case presentation and literature review.
AB  - In the past decade opioid pain reliever misuse among the U.S. population has
      increased to epidemic proportions. While the U.S. has only 4% of the world's
      population, Americans consume 86% of the world's opioids. In 2011, approximately
      13 million people (5% of the U.S. population) reported nonmedical use of
      prescription opioids, which are now the second most commonly abused class of drug
      behind cannabis. There has been little in the way of formal study examining the
      association between mental illness and prescription opiate abuse, but preliminary
      evidence suggests a strong association. Neurobiological processes involved in
      psychosis and opiate abuse may partially explain this association. Despite
      compelling evidence of the growth in opiate misuse and the potential relationship
      with mental illness, patients with mental disorders and/or substance abuse are
      routinely excluded from randomized trials, making it impossible to better
      understand these phenomena. Treatment guidelines, especially regarding opioid
      agonists such as methadone and buprenorphine for people with mental illness, are
      woefully inadequate. We present the case of a young man with schizoaffective
      disorder who sustained an injury and developed chronic back pain. Opioids were
      prescribed and he quickly progressed to abusing increasing doses of opioids,
      which eventually led to daily heroin use. The young man struggled with repeated
      relapses, serious use-related consequences and suicide attempts. This case
      highlights the role of chronic pain and opioid prescribing, the segue from
      prescribed use to abuse and dependence, and the transition to heroin use. It
      demonstrates the difficulty patients may have in obtaining adequate treatment for
      co-occurring mental illness and substance abuse and how outcomes are improved
      when treatment is integrated to address both disorders. Comprehensive treatment
      must involve a combination of case management and medical management, including
      possible opioid replacement therapy. 

PMID- 25392063
TI  - Assessment of lower limb flow and adequate intra-arterial papaverine doses to
      achieve maximal hyperemia in elder subjects.
AB  - Previous studies reported that invasive physiological assessment for significance
      of the lesions in the patients with claudication under the condition of
      pharmacological hyperemia was important to identify the patients who will benefit
      from revascularization. However, the maximal hyperemic response in lower limb and
      the method to induce maximum dilatation of vascular bed in lower limb were not
      well established. The aim of this study was to investigate the range of maximal
      hyperemic response in lower limb of the normal subjects and to identify the ideal
      lower limb vasodilatory stimulation. Twelve limbs without stenotic lesions from
      12 subjects (average age: 72 +/- 6 years) were analyzed. Thermodilution-derived
      mean transit time (Tmn) was obtained at baseline and during pharmacological
      hyperemia with incremental dose of intra-arterial papaverine (10, 20, 30, and 40
      mg) using a 0.014-inch pressure/temperature sensor-tipped wire in the superficial
      femoral artery (SFA). Percent increase in blood flow (%IBF) of lower limb was
      defined as the ratio between baseline Tmn and hyperemic Tmn. Mean ankle brachial
      index score of the subjects was 1.14 +/- 0.09. The %IBF values were enhanced by
      papaverine in a dose-dependent manner. A dose of 30 mg of intra-arterial
      papaverine was sufficient to achieve maximum hyperemia (%IBF: range 219-769 %).
      In conclusion, the increase in blood flow of lower limb during maximal hyperemia
      varied between individuals and maximal hyperemia can be achieved with 30 mg of
      papaverine for the SFA lesion. 

PMID- 25392064
TI  - Genital herpes and its treatment in relation to preterm delivery.
AB  - To examine the risks of genital herpes and antiherpes treatment during pregnancy
      in relation to preterm delivery (PTD), we conducted a multicenter, member-based
      cohort study within 4 Kaiser Permanente regions: northern and southern
      California, Colorado, and Georgia. The study included 662,913 mother-newborn
      pairs from 1997 to 2010. Pregnant women were classified into 3 groups based on
      genital herpes diagnosis and treatment: genital herpes without treatment, genital
      herpes with antiherpes treatment, and no herpes diagnosis or treatment (unexposed
      controls). After controlling for potential confounders, we found that compared
      with being unexposed, having untreated genital herpes during first or second
      trimester was associated with more than double the risk of PTD (odds ratio (OR) =
      2.23, 95% confidence interval (CI): 1.80, 2.76). The association was stronger for
      PTD due to premature rupture of membrane (OR = 3.57, 95% CI: 2.53, 5.06) and for
      early PTD (<=35 weeks gestation) (OR = 2.87, 95% CI: 2.22, 3.71). In contrast,
      undergoing antiherpes treatment during pregnancy was associated with a lower risk
      of PTD compared with not being treated, and the PTD risk was similar to that
      observed in the unexposed controls (OR = 1.11, 95% CI: 0.89, 1.38). The present
      study revealed increased risk of PTD associated with genital herpes infection if
      left untreated and a potential benefit of antiherpes medications in mitigating
      the effect of genital herpes infection on the risk of PTD.

PMID- 25392065
TI  - Transcriptome analysis of a subtropical deciduous tree: autumn leaf senescence
      gene expression profile of Formosan gum.
AB  - Autumn leaf senescence is a spectacular natural phenomenon; however, the
      regulation networks controlling autumnal colors and the leaf senescence program
      remain largely unelucidated. Whether regulation of leaf senescence is similar in
      subtropical deciduous plants and temperate deciduous plants is also unknown. In
      this study, the gene expression of a subtropical deciduous tree, Formosan gum
      (Liquidambar formosana Hance), was profiled. The transcriptomes of April leaves
      (green leaves, 'G') and December leaves (red leaves, 'R') were investigated by
      next-generation gene sequencing. Out of 58,402 de novo assembled contigs, 32,637
      were annotated as putative genes. Furthermore, the L. formosana-specific
      microarray designed based on total contigs was used to extend the observation
      period throughout the growing seasons of 2011-2013. Network analysis from the
      gene expression profile focused on the genes up-regulated when autumn leaf
      senescence occurred. LfWRKY70, LfWRKY75, LfWRKY65, LfNAC1, LfSPL14, LfNAC100 and
      LfMYB113 were shown to be key regulators of leaf senescnece, and the genes
      regulated by LfWRKY75, LfNAC1 and LfMYB113 are candidates to link chlorophyll
      degradation and anthocyanin biosynthesis to senescence. In summary, the gene
      expression profiles over the entire year of the developing leaf from subtropical
      deciduous trees were used for in silico analysis and the putative gene regulation
      in autumn coloration and leaf senescence is discussed in this study.

PMID- 25392066
TI  - Protein-protein interactions among xyloglucan-synthesizing enzymes and formation
      of Golgi-localized multiprotein complexes.
AB  - Arabidopsis thaliana xyloglucan has an XXXG structure, with branches of xylosyl
      residues, beta-D-galacosyl-(1,2)-alpha-d-xylosyl motifs and fucosylated beta-D
      galactosyl-(1,2)-alpha-D-xylosyl motifs. Most of the enzymes involved in
      xyloglucan biosynthesis in Arabidopsis have been identified, including the glucan
      synthase CSLC4 (cellulose synthase-like C4), three xylosyltransferases (XXT1,
      XXT2 and XXT5), two galactosyltransferases (MUR3 and XLT2) and the
      fucosyltransferase FUT1. The XXTs and CSLC4 form homo- and heterocomplexes and
      were proposed to co-localize in the same complex, but the organization of the
      other xyloglucan-synthesizing enzymes remains unclear. Here we investigate
      whether the glycosyltransferases MUR3, XLT2 and FUT1 interact with the XXT-CSLC4
      complexes in the Arabidopsis Golgi. We used co-immunoprecipitation and
      bimolecular fluorescence complementation, with signal quantification by flow
      cytometry, to demonstrate that CSLC4 interacts with MUR3, XLT2 and FUT1. FUT1
      forms homocomplexes and interacts with MUR3, XLT2, XXT2 and XXT5. XLT2 interacts
      with XXT2 and XXT5, but MUR3 does not. Co-immunoprecipitation assays showed that
      FUT1 forms a homocomplex through disulfide bonds, and formation of the
      heterocomplexes does not involve covalent interactions. In vitro pull-down assays
      indicated that interactions in the FUT1-MUR3 and FUT1-XXT2 complexes occur
      through the protein catalytic domains. We propose that enzymes involved in
      xyloglucan biosynthesis are functionally organized in multiprotein complexes
      localized in the Golgi.

PMID- 25392067
TI  - The matrix polysaccharide (1;3,1;4)-beta-D-glucan is involved in silicon
      dependent strengthening of rice cell wall.
AB  - Poales [represented by rice (Oryza sativa L.)] in angiosperms and Equisetum
      (horsetails) in Pteridophytes are two major groups of heavy silicon (Si)
      accumulators. In rice, Si is polymerized preferentially in the epidermal cell
      wall, forming Si-cuticle double layers and Si-cellulose double layers beneath the
      cuticle. This Si layer is thought to exert various beneficial effects on the
      growth and development of land plants. Although the recent discovery of the
      influx and efflux transporters of silicic acid has shed some light on the
      molecular mechanisms of Si uptake and transport in rice, the mechanism underlying
      the final incorporation of polymerized Si into the cell wall remains elusive.
      Despite their phylogenetic distance, the cell walls of the two Si accumulators,
      Poales and Equisetum, share another common component, i.e. (1;3,1;4)-beta-D
      glucan, also known as mixed-linkage glucan (MLG), a matrix polysaccharide not
      found in other plants. Based on this coincidence, a possible correlation between
      the functions of Si and MLG in the cell wall has been suggested, but no
      experimental evidence has been obtained in support of this functional
      correlation. Here, we present an analysis of the correlative action of Si and MLG
      on the mechanical properties of leaf blades using a transgenic rice line in which
      the MLG level was reduced by overexpressing EGL1, which encodes (1;3,1;4)-beta-D
      glucanase. The reduction in MLG did not affect total Si accumulation, but it
      significantly altered the Si distribution profile and reduced the Si-dependent
      mechanical properties of the leaf blades, strongly suggesting a functional
      correlation between Si and MLG.

PMID- 25392068
TI  - Multigene knockout utilizing off-target mutations of the CRISPR/Cas9 system in
      rice.
AB  - The clustered regularly interspaced short palindromic repeat (CRISPR)-associated
      endonuclease 9 (CRISPR/Cas9) system has been demonstrated to be a robust genome
      engineering tool in a variety of organisms including plants. However, it has been
      shown that the CRISPR/Cas9 system cleaves genomic DNA sequences containing
      mismatches to the guide RNA strand. We expected that this low specificity could
      be exploited to induce multihomeologous and multiparalogous gene knockouts. In
      the case of polyploid plants, simultaneous modification of multiple homeologous
      genes, i.e. genes with similar but not identical DNA sequences, is often needed
      to obtain a desired phenotype. Even in diploid plants, disruption of
      multiparalogous genes, which have functional redundancy, is often needed. To
      validate the applicability of the CRISPR/Cas9 system to target mutagenesis of
      paralogous genes in rice, we designed a single-guide RNA (sgRNA) that recognized
      20 bp sequences of cyclin-dependent kinase B2 (CDKB2) as an on-target locus.
      These 20 bp possess similarity to other rice CDK genes (CDKA1, CDKA2 and CDKB1)
      with different numbers of mismatches. We analyzed mutations in these four CDK
      genes in plants regenerated from Cas9/sgRNA-transformed calli and revealed that
      single, double and triple mutants of CDKA2, CDKB1 and CDKB2 can be created by a
      single sgRNA.

PMID- 25392069
TI  - Comparison of factors associated with desaturation in prehospital emergency
      anaesthesia in primary and secondary retrievals.
AB  - OBJECTIVE: To investigate the incidence and factors associated with desaturation
      related to emergency intubations within an aeromedical retrieval service
      pertaining to both primary prehospital and secondary interhospital missions.
      METHODS: A retrospective analysis of all rapid sequence intubations (RSI) was
      performed by the Emergency Medical Retrieval Service over a 4.5-year period (June
      2008-November 2012). For each RSI, clinical indication for RSI, age, sex,
      traumatic or medical diagnosis, team leader specialty, Cormack and Lehane (C-L)
      grade of laryngoscope view, attempts at intubation, desaturation and hypotension
      was analysed. A multiple logistical regression analysis was constructed using the
      factors identified in the univariate logistical regression using a backward
      stepwise model. RESULTS: During the study period, a total of 1423 missions were
      carried out. 1088 of these missions were secondary retrievals and 335 were
      primary prehospital missions. 208 patients required RSI during the study period.
      Our data show that 15.4% of all anaesthetised patients had a desaturation during
      emergency anaesthesia. This included 11.3% of primary prehospital patients and
      16.8% of secondary retrieval patients (95% CI -5.0% to 15.8%). 7.9% of patients
      had an episode of hypotension during RSI. Univariate associations for
      desaturation were more than one attempt at intubation and a C-L grade III or
      worse view. Multivariate analysis showed only C-L grade III or worse view as an
      independent risk factor for desaturation. CONCLUSIONS: Desaturation was not more
      common in secondary retrieval patients. Multiple attempts at intubation and a
      poor laryngoscopic view at intubation were associated with desaturation during
      RSI.

PMID- 25392070
TI  - Use of proton pump inhibitors is associated with anemia in cardiovascular
      outpatients.
AB  - BACKGROUND: Proton pump inhibitors (PPI) are frequently prescribed in combination
      with aspirin for preventing peptic ulcer in patients with atherosclerotic
      diseases. In contrast, long-term use of PPI has been suggested to be associated
      with iron or vitamin B12 deficiency. The effect of PPI on hemoglobin (Hb)
      concentration, however, has not been clarified in cardiovascular outpatients.
      METHODS AND RESULTS: We retrospectively investigated the clinical characteristics
      of 278 continuous outpatients who received blood test including complete blood
      count and serum creatinine concentration (mean age, 69.9 +/- 10.8 years; male,
      68.7%). The frequency of anemia was 51% in patients receiving PPI and 19% in
      those not receiving PPI (chi-squared test, P<0.001). On multivariate analysis
      female sex (P<0.001), peripheral artery disease (P=0.003), PPI (P=0.003), low
      white blood cell count (P=0.004), old age (P=0.007), and low estimated glomerular
      filtration rate (P=0.010) were independently associated with low Hb. Among these
      patients, we investigated the change in Hb after the initiation of PPI in 36
      patients for whom data on Hb level within 1 year before and within 1 year after
      the initiation of PPI were available. Mean decrease in Hb after the initiation of
      PPI was 0.38 +/- 0.87 g/dl (95% confidence interval: -0.67 to -0.09 g/dl).
      CONCLUSIONS: Use of PPI was associated with anemia in Japanese cardiovascular
      outpatients.

PMID- 25392071
TI  - Assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial
      infarction - ALPS-AMI study.
AB  - BACKGROUND: Statins reduce the incidence of cardiovascular events, but no
      randomized trial has investigated the best statins for secondary prevention. We
      compared the efficacy of hydrophilic pravastatin with that of lipophilic
      atorvastatin in patients with acute myocardial infarction (AMI). METHODS AND
      RESULTS: A prospective, multicenter study enrolled 508 patients (410 men; mean
      age, 66.0 +/- 11.6 years) with AMI who were randomly assigned to atorvastatin
      (n=255) or pravastatin (n=253). The target control level of low-density
      lipoprotein cholesterol (LDL-C) was <100 mg/dl, and patients were followed for 2
      years. The primary endpoint was the composite of death due to any cause, non
      fatal myocardial infarction, non-fatal stroke, unstable angina or congestive
      heart failure requiring hospital admission, or any type of coronary
      revascularization. The primary endpoint occurred in 77 patients (30.4%) and in 80
      patients (31.4%) in the pravastatin and atorvastatin groups, respectively (hazard
      ratio, 1.181; 95% confidence interval: 0.862-1.619; P=0.299), whereas greater
      reductions in serum total cholesterol and LDL-C were achieved in the atorvastatin
      group (P<0.001 for each). Changes in hemoglobin A1c, brain natriuretic peptide,
      and creatinine were not significant between the 2 regimens, and safety and
      treatment adherence were similar. CONCLUSIONS: On 2-year comparison of
      hydrophilic and lipophilic statins there was no significant difference in
      prevention of secondary cardiovascular outcome.

PMID- 25392072
TI  - Postoperative hyperglycemia and atrial fibrillation after coronary artery bypass
      graft surgery.
AB  - BACKGROUND: Postoperative atrial fibrillation (AF) is a common complication
      following coronary artery bypass grafting (CABG). We investigated the risk
      factors for postoperative AF and analyzed the relationship between blood sugar
      concentration (BS) and AF after CABG. METHODS AND RESULTS: A total of 199
      consecutive patients who underwent isolated CABG were retrospectively examined
      and classified according to the presence (n=95) or absence (n=104) of
      postoperative AF. On univariate analysis mean postoperative BS (P<0.001),
      postoperative drainage volume (P<0.001), age (P=0.034), presence of diabetes
      mellitus (DM; P=0.004), and postoperative estimated glomerular filtration rate
      (P=0.032) were significant risk factors for postoperative AF. On multivariate
      analysis mean postoperative BS (OR, 1.041; 95% CI: 1.008-1.079; P<0.001),
      postoperative drainage volume (OR, 1.003; 95% CI: 1.001-1.006; P=0.001), and age
      (OR, 1.040; 95% CI: 1.002-1.083; P=0.041) were significant risk factors for
      postoperative AF. Postoperative AF often occurred in patients with high
      postoperative BS, irrespective of DM. The BS cut-off that predicted postoperative
      AF occurrence was 180 mg/dl. A strong positive correlation existed between the
      time of the maximum postoperative BS and AF onset time (rho=0.746). CONCLUSIONS:
      Mean postoperative BS and postoperative drainage volume are risk factors for AF
      after CABG. AF was strongly associated with maximum postoperative BS. Intensive
      glycemic control could reduce AF occurrence after CABG.

PMID- 25392073
TI  - Sperm DNA fragmentation index and pregnancy outcome after IVF or ICSI: a meta
      analysis.
AB  - PURPOSE: The purpose of this study was to carry out a meta-analysis for a
      comprehensive understanding and estimation of the association between sperm DNA
      Fragmentation Index (DFI) and pregnancy outcome after in vitro fertilization
      (IVF) or intracytoplasmic sperm injection (ICSI) treatment. METHODS: Studies
      concerning the link of DFI with pregnancy outcome were included after literature
      search of database PUBMED, EMBASE, MEDLINE. Related information was extracted
      from the eligible studies by two independent authors and a meta-analysis was
      conducted by using STATA 12.0 software. Pregnancy outcomes consisted of
      biochemical pregnancy (BP), clinical pregnancy (CP) and pregnancy loss (PL). The
      studies included for meta-analysis were divided into three groups according to
      the DFI threshold value (DFI >27 %, 15-27 %, <=15 % group). The odds ratio (OR )
      and their 95 % confidence intervals (95 % CIs) were used to evaluate the
      association between DFI and pregnancy outcome. RESULTS: Twenty articles were
      included in our meta-analysis. The results indicated that infertile couples were
      more likely to get pregnant if DFI was less than threshold value (For threshold
      value > 27 % and 15-27 % group, combined overall OR (95 % CI) = 1.437 (1.186
      1.742), 1.639 (1.093-2.459) respectively). However, when stratified by DFI
      detection methods, using sperm chromatin structure assay (SCSA) as the DFI test
      method, the results indicated a similar CP rate between groups with a high DFI or
      a lower DFI value (SCSA, For threshold value >27 % and 15-27 % group, combined
      overall OR (95 % CI) = 1.242(0.978-1.577), 1.480(0.921-2.377) respectively). The
      meta-analysis based on BP (overall OR (95 % CI) = 0.952 (0.697-1.302)) and
      PL((For DFI >27 %, 15-27 %, <=15 % group, OR (95 % CI) = 0.786 (0.491-1.258),
      1.509 (0.655-3.476), (0.538 (0.264-1.097) respectively) outcome yielded
      nonsignificant results. CONCLUSIONS: The predication value of DFI for IVF or ICSI
      outcome is not confirmed in our meta-analysis. Further better designed studies
      with larger subjects involved are needed to better address this issue.

PMID- 25392074
TI  - Assessment of vitrification outcome by xenotransplantation of ovarian cortex
      pieces in gamma-irradiated mice: morphological and molecular analyses of
      apoptosis.
AB  - PURPOSE: The aim of this study was the investigation of caspase-3/7 activity and
      apoptosis related gene expression after vitrification and xenotransplantation of
      human ovarian fragments. METHODS: Ovarian specimens were obtained from normal
      female-to-male transsexual women during laparoscopic surgery and cut into small
      pieces and were considered as vitrified and non-vitrified groups. The
      morphological study, terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) assay, caspase-3/7 activity and apoptosis related gene expression
      analysis were done in both non-vitrified and vitrified groups in two steps
      (before transplantation of ovarian tissues and 30 days after transplantation).
      RESULT(S): In spite of high rate of normal follicles in both non-transplanted
      tissues these rates were significantly decreased in vitrified and non-vitrified
      grafted tissues, moreover grafted-vitrified tissue showed significantly less
      normal follicles than grafted-non-vitrified group (P < 0.05). The expression of
      some pro and anti-apoptotic genes in vitrified-warmed tissues were not changed
      compared to non-vitrified ones but the expression of Fas and caspase8 was
      increased and the expression of BRIC5 was decreased in this group (P < 0.05). In
      transplanted vitrified group the Bcl2, FasL and BRIC5 gene expression was high
      and caspase8 was low (P < 0.05). The expression of all genes in both grafted
      groups was more than non-grafted tissues except for caspase8 (P < 0.05). The
      TUNEL positive signals and caspase-3/7 activity were increased in both grafted
      groups compared to non-grafted groups and this enzyme activity in grafted
      vitrified group was more than grafted-non-vitrified group (P < 0.05).
      CONCLUSION(S): This study provides the first evidence on the significant effect
      of vitrification on follicular apoptosis of grafted human ovarian tissue at mRNA
      level. The signs of follicular survival or degeneration detected by morphological
      assessment and caspase-3/7 activity were closely correlated to the changes in
      expression of apoptosis-related genes.

PMID- 25392075
TI  - Prospective cohort study of the effectiveness of varenicline versus nicotine
      replacement therapy for smoking cessation in the "real world".
AB  - BACKGROUND: It is important to know the comparative effectiveness of varenicline
      and nicotine replacement therapy (NRT) for smoking cessation when prescribed
      under routine circumstances and in the general population. Previous estimates
      relied on cross-sectional data. The objective of the current study was to use
      longitudinal data to compare the abstinence rates of smokers trying to stop
      having used varenicline versus NRT on prescription (Rx) when provided with
      minimal professional support in the general population while adjusting for key
      potential confounders. METHODS: Prospective cohort study in 270 adults who
      participated in a household survey, smoked at baseline, responded to the 6-month
      follow-up survey, and made at least one quit attempt between the two measurements
      with either varenicline or NRT Rx in their most recent quit attempt. The main
      outcome measure was self-reported abstinence up to the time of the survey,
      adjusted for key potential confounders including cigarette dependence (measured
      at baseline). RESULTS: Users of varenicline were younger, reported more time
      spent with urges to smoke at baseline, and were less likely to stop abruptly
      during their last quit attempt (all p < 0.01). The adjusted odds of abstinence in
      users of varenicline were 3.83 (95% CI = 1.88-7.77) times higher compared with
      users of NRT Rx. CONCLUSIONS: Varenicline use with minimal professional support
      in the general population of smokers appears more effective than NRT Rx in
      achieving abstinence.

PMID- 25392076
TI  - Factors associated with prolonged anesthesia recovery following laparoscopic
      bariatric surgery: a retrospective analysis.
AB  - BACKGROUND: Phase I postanesthesia recovery is often prolonged after laparoscopic
      bariatric surgery. We hypothesized that postoperative respiratory depression is a
      major contributor to this delayed recovery. METHODS: Medical records of all
      patients who had a laparoscopic bariatric surgical operation from January 1,
      2009, to December 31, 2012, were reviewed for clinical, anesthetic, and
      postanesthesia variables. Recoveries were defined as discharge from the recovery
      room in <=90 min and in >90 min (prolonged postanesthesia recovery). We compared
      characteristics of patients without prolonged recovery to those with prolonged
      recovery. RESULTS: Of 781 bariatric patients, 304 (38.9 %) had prolonged
      recovery. These patients had more respiratory depression (29 vs 6 patients), more
      postoperative nausea and vomiting (106 vs 92 patients), more treatments of
      hypertension in the recovery room (49 vs 33 patients), and more opioid treatment
      (median intravenous morphine equivalents [interquartile range], 10.0 [3.0-15.0]
      vs 5.0 [0.0-10.5]) (P < 0.001 for all). On multivariable analysis, preoperative
      history of hypertension (P = 0.03), fewer prophylactic antiemetics received (P =
      0.02), and longer surgical duration (P = 0.03) were associated with prolonged
      postanesthesia recovery. CONCLUSIONS: Inadequate antiemetic prophylaxis and the
      treatment of postoperative hypertension were associated with prolonged
      postanesthesia recovery. Surprisingly, diagnosis of obstructive sleep apnea was
      not associated with prolonged recovery, which may be attributable to use of
      continuous positive airway pressure devices following emergence from anesthesia.
      Prolonged recovery in patients treated for hypertension may be related to
      institutional guidelines that require additional monitoring time after these
      medications are administered.

PMID- 25392077
TI  - Second-stage robot-assisted biliopancreatic diversion with duodenal switch after
      sleeve gastrectomy.
AB  - Biliopancreatic diversion (BPD) was initially described in 1979 and consisted of
      a distal gastrectomy with a 250-mL stomach pouch and a distal intestinal bypass
      with a 50 to 100-cm common channel resulting in malabsorption of dietary fat
      (Scopinaro et al. Br J Surg. 66(9):618-20, 1979). Later, several modifications
      (sleeve gastrectomy, pylorus preservation, and duodenal switch) were proposed to
      improve incidence of postoperative dumping syndrome, diarrhea, and anastomotic
      ulcerations (Lagace et al. Obes Surg. 5(4):411-8, 1995). Gagner et al. developed
      a simplified and reproducible approach for laparoscopic BPD with duodenal switch
      (BPD-DS) after sleeve gastrectomy (Ren et al. Obes Surg. 10(6): 514-23, 2000).
      BPD-DS has been considered as one of the most difficult bariatric procedures for
      its surgical complexity and postoperative metabolic complications management. In
      this regard, the number of BPD-DS has remained extremely low (<4 %). We
      hypothesize that robotic approach could facilitate the feasibility of BPD-DS
      procedure. In this multimedia video (8 min), we present a step-by-step robotic
      BPD-DS.

PMID- 25392078
TI  - Examination of the Beck Depression Inventory-II Factor Structure Among Bariatric
      Surgery Candidates.
AB  - BACKGROUND: The Beck Depression Inventory-II (BDI-II) is frequently used to
      evaluate bariatric patients in clinical and research settings; yet, there are
      limited data regarding the factor structure of the BDI-II with a bariatric
      surgery population. METHODS: Exploratory factor analysis (EFA) using principal
      axis factoring with oblimin rotation was employed with data from 1228 consecutive
      presurgical bariatric candidates. Independent t tests were used to examine
      potential differences between sexes. Confirmatory factor analysis (CFA) was
      conducted with the next 383 consecutive presurgical patients to evaluate the
      proposed model based on EFA results. RESULTS: EFA revealed three factors:
      negative perceptions, diminished vigor, and cognitive dysregulation, each with
      adequate internal consistency. Six BDI-II items did not load significantly on any
      of the three factors. CFA results largely supported the proposed model.
      CONCLUSIONS: Results suggest that dimensions of depression for presurgical
      bariatric candidates vary from other populations and raise important caveats
      regarding the utility of the BDI-II in bariatric research.

PMID- 25392079
TI  - Effect of Laparoscopic Roux-en-Y Gastric Bypass Surgery on Obstructive Sleep
      Apnea in a Chinese Population with Obesity and T2DM.
AB  - BACKGROUND: Bariatric surgery has been reported to be an effective treatment for
      obstructive sleep apnea (OSA). However, this evidence was not enough for
      different populations. Thus, we conducted a follow-up study to evaluate the
      effect of bariatric surgery on OSA in a Chinese population with obesity and type
      2 diabetes mellitus (T2DM). METHODS: From May 2011 to March 2014, 72 consecutive
      subjects with obesity and T2DM were recruited for this study. Before and at least
      6 months after the laparoscopic Roux-en-Y gastric bypass (LYGB) surgery, all
      subjects were asked to undergo a polysomnography test. During the sleep center
      visit, anthropometric characteristic data, blood samples, and sleep
      questionnaires were collected. RESULTS: In total, 44 Chinese participants with
      OSA were included in the study. Compared with baseline data, the postoperative
      anthropometric characteristics, blood measurements, and sleep recording data,
      such as weight, apnea hypopnea index (AHI), and insulin resistance index,
      differed significantly (p < 0.001). The change in AHI was correlated
      significantly with preoperative weight (r = 0.298, p < 0.05), preoperative AHI (r
      = 0.729, p < 0.001), preoperative waist circumference (r = 0.307, p < 0.05), and
      preoperative insulin resistance (IR) index (r = -0.301, p < 0.05). Postoperative
      AHI was correlated significantly with age (r = 0.039, p = 0.039) and preoperative
      AHI (r = 0.445, p = 0.002), and the following prediction model was generated:
      log10 (postoperative AHI) = 0.626 * log10 (preoperative AHI) +0.010 * age -0.581.
      CONCLUSIONS: Our findings indicate that LYGB could be an effective therapeutic
      intervention in the management of OSA for patients with both obesity and T2DM,
      and the preoperative AHI and age might be important factors that influence the
      effort of LYGB.

PMID- 25392080
TI  - Clinical guideline SEOM: cancer of unknown primary site.
AB  - Cancer of unknown primary site is a histologically confirmed cancer which is
      manifested in advanced stage, with no identifiable primary site after the use of
      standard diagnostic procedures. Patients are initially placed into one of
      categories based upon the examination of the initial biopsy: adenocarcinoma,
      squamous cell carcinoma, neuroendocrine carcinoma and poorly differentiated
      carcinoma. Appropriate patient management requires an understanding of several
      clinicopathologic features that help to identify several subsets of patients with
      more responsive tumors. 

PMID- 25392081
TI  - SEOM guidelines 2014: improving quality to increase its usefulness.

PMID- 25392082
TI  - Chlamydia infection depends on a functional MDM2-p53 axis.
AB  - Chlamydia, a major human bacterial pathogen, assumes effective strategies to
      protect infected cells against death-inducing stimuli, thereby ensuring
      completion of its developmental cycle. Paired with its capacity to cause
      extensive host DNA damage, this poses a potential risk of malignant
      transformation, consistent with circumstantial epidemiological evidence. Here we
      reveal a dramatic depletion of p53, a tumor suppressor deregulated in many
      cancers, during Chlamydia infection. Using biochemical approaches and live
      imaging of individual cells, we demonstrate that p53 diminution requires
      phosphorylation of Murine Double Minute 2 (MDM2; a ubiquitin ligase) and
      subsequent interaction of phospho-MDM2 with p53 before induced proteasomal
      degradation. Strikingly, inhibition of the p53-MDM2 interaction is sufficient to
      disrupt intracellular development of Chlamydia and interferes with the pathogen's
      anti-apoptotic effect on host cells. This highlights the dependency of the
      pathogen on a functional MDM2-p53 axis and lends support to a potentially pro
      carcinogenic effect of chlamydial infection. 

PMID- 25392083
TI  - Elevation of BDNF exon I-specific transcripts in the frontal cortex and midbrain
      of rat during spontaneous morphine withdrawal is accompanied by enhanced pCreb1
      occupancy at the corresponding promoter.
AB  - Brain-derived neurotrophic factor (BDNF) is believed to play a crucial role in
      the mechanisms underlying opiate dependence; however, little is known about
      specific features and mechanisms regulating its expression in the brain under
      these conditions. The aim of this study was to investigate the effects of acute
      morphine intoxication and withdrawal from chronic intoxication on expression of
      BDNF exon I-, II-, IV-, VI- and IX-containing transcripts in the rat frontal
      cortex and midbrain. We also have studied whether alterations of BDNF exon
      specific transcripts are accompanied by changes in association of well-known
      transcriptional regulators of BDNF gene-phosphorylated (active form) cAMP
      response element binding protein (pCreb1) and methyl-CpG binding protein 2
      (MeCP2) with corresponding regulatory regions of the BDNF gene. Acute morphine
      intoxication did not affect levels of BDNF exons in brain regions, while
      spontaneous morphine withdrawal in dependent rats was accompanied by an elevation
      of the BDNF exon I-containing mRNAs both in the frontal cortex and midbrain.
      During spontaneous morphine withdrawal, increased associations of pCreb1 were
      found with promoter of exon I in the frontal cortex and promoters of exon I, IV
      and VI in the midbrain. The association of MeCP2 with BDNF promoters during
      spontaneous morphine withdrawal did not change. Thus, BDNF exon-specific
      transcripts are differentially expressed in brain regions during spontaneous
      morphine withdrawal in dependent rats and pCreb1 may be at least partially
      responsible for these alterations. 

PMID- 25392084
TI  - Morphing and vectoring impacting droplets by means of wettability-engineered
      surfaces.
AB  - Driven by its importance in nature and technology, droplet impact on solid
      surfaces has been studied for decades. To date, research on control of droplet
      impact outcome has focused on optimizing pre-impact parameters, e.g., droplet
      size and velocity. Here we follow a different, post-impact, surface engineering
      approach yielding controlled vectoring and morphing of droplets during and after
      impact. Surfaces with patterned domains of extreme wettability (high or low) are
      fabricated and implemented for controlling the impact process during and even
      after rebound--a previously neglected aspect of impact studies on non-wetting
      surfaces. For non-rebound cases, droplets can be morphed from spheres to complex
      shapes--without unwanted loss of liquid. The procedure relies on competition
      between surface tension and fluid inertial forces, and harnesses the naturally
      occurring contact-line pinning mechanisms at sharp wettability changes to create
      viable dry regions in the spread liquid volume. Utilizing the same forces central
      to morphing, we demonstrate the ability to rebound orthogonally-impacting
      droplets with an additional non-orthogonal velocity component. We theoretically
      analyze this capability and derive a We(-.25) dependence of the lateral
      restitution coefficient. This study offers wettability-engineered surfaces as a
      new approach to manipulate impacting droplet microvolumes, with ramifications for
      surface microfluidics and fluid-assisted templating applications.

PMID- 25392086
TI  - Using phase shift Granger causality to measure directed connectivity in EEG
      recordings.
AB  - Cortical activity is maintained by neural networks working in tandem.
      Electroencephalographic (EEG) signals across two sites are said to be coherent
      with one another when they show consistent phase relations. However, periods of
      desynchrony beginning with a shift in phase relations are a necessary aspect of
      information processing. Traditional measures of EEG coherence lack the temporal
      resolution required to divide the relationship between two signals into periods
      of synchrony and desynchrony and are unable to specify the direction of
      information transmission (i.e., which site is leading and which is lagging), a
      goal referred to as directed connectivity. In this article, the authors introduce
      a novel method of measuring directed connectivity by applying the framework of
      Granger causality to phase shift events which are estimated with high temporal
      resolution. A simulation study is used to verify that the proposed method is able
      to identify connectivity patterns in situations similar to EEG recordings, such
      as high levels of noise and linear source mixing. Their method is able to
      correctly identify both the existence and direction of information transfer, and
      that the existence of spatiotemporal noise serves to reduce the spread of shift
      identification due to volume conduction. To demonstrate the method on real data,
      it is applied to EEG recordings from 18 adolescents during a resting period and
      auditory and visual vigilance tasks. Their new measure, Phase Shift Granger
      Causality (PSGC), is able to clearly distinguish between the resting task and the
      active tasks. The latter have higher rates of connectivity overall and
      specifically more long-range connections. As expected, the resting task appears
      to activate more localized neural circuitry, whereas the active tasks appear to
      increase communication across several neural regions involved in vigilance tasks.
      The vigilance tasks also showed significantly higher clustering coefficients than
      the resting task, a property associated with small-world networks.

PMID- 25392085
TI  - Association study of H2AFZ with schizophrenia in a Japanese case-control sample.
AB  - It is widely accepted that malfunction of the N-methyl-D-aspartate (NMDA)-type
      glutamate receptor may be involved in the pathophysiology of schizophrenia.
      Several recent microRNA (miRNA) studies have demonstrated that the expression of
      the glutamate system-related miR-132 and miR-212 is changed in postmortem
      schizophrenic brains. Here we attempted to obtain further insight into the
      relationships among schizophrenia, the NMDA receptor, the molecular cascades
      controlled by these miRNAs and commonly predicted target genes of the two miRNAs.
      We focused on the H2AFZ (encoding H2A histone family, member Z) gene, whose
      expression was shown in our screening study to be modified by a
      schizophrenomimetic NMDA antagonist, phencyclidine. By performing polymerase
      chain reaction with fluorescent signal detention using the TaqMan system, we
      examined four tag single nucleotide polymorphisms (SNPs; SNP01-04) located around
      and within the H2AFZ gene for their genetic association with schizophrenia. The
      subjects were a Japanese cohort (2,012 patients with schizophrenia and 2,170
      control subjects). We did not detect any significant genetic association of these
      SNPs with schizophrenia in this cohort. However, we observed a significant
      association of SNP02 (rs2276939) in the male patients with schizophrenia (allelic
      P = 0.003, genotypic P = 0.008). A haplotype analysis revealed that haplotypes
      consisting of SNP02-SNP03 (rs10014424)-SNP04 (rs6854536) also showed a
      significant association in the male patients with schizophrenia (P = 0.018).
      These associations remained significant even after correction for multiple
      testing. The present findings suggest that the H2AFZ gene may be a susceptibility
      factor in male subjects with schizophrenia, and that modification of the H2AFZ
      signaling pathway warrants further study in terms of the pathophysiology of
      schizophrenia.

PMID- 25392087
TI  - Kinesiophobia negatively influences recovery of joint function following total
      knee arthroplasty.
AB  - BACKGROUND: The influence of kinesiophobia on disability in patients with knee
      osteoarthritis is known, but its influence on functional recovery after total
      knee arthroplasty remains unexplored. AIMS: To assess the influence of
      kinesiophobia on functional recovery following total knee arthroplasty (TKA) in
      patients with knee osteoarthritis and to investigate if kinesiophobia was more
      common in obese patients than in non-obese patients. DESIGN: Cohort study.
      SETTING: Inpatients of the Physical Medicine and Rehabilitation unit of the
      Chateau-Renault hospital (France). POPULATION: The study included 89 consecutive
      patients (mean age = 72.6 years) hospitalized for postoperative rehabilitation
      after TKA. All patients completed the study. METHODS: We evaluated functional
      outcome by testing maximum passive flexion, pain intensity, the duration of
      hospitalization, and performance in a six minute walk test. Kinesiophobia was
      assessed by the Tampa Scale for Kinesiophobia (TSK) score. Obesity was assessed
      by calculation of body mass index (BMI). A Stepwise multiple linear regression
      was used to determine significant independent predictors of the distance at the
      six minute walk test. RESULTS: During the six minute walk test, patients without
      kinesiophobia walked significantly farther than patients with kinesiophobia
      (309.5 [83.6] m vs. 264.8 [96.5] m, P=0.048). There were no significant
      differences in the duration of hospitalization, the maximum passive flexion, or
      pain intensity between the two groups. The best multivariate model of factors
      associated with the performance in the 6 minute walk test included the Lequesne's
      score before surgery, the degree of active extension of the knee at the beginning
      of hospitalization, the TSK scores (total score, classification with the TSK
      score, "avoidance" subscale score). The overall TSK score did not differ between
      the obese and non-obese groups. CONCLUSION: Our study is consistent with previous
      reports that cognitive and behavioral maladaptative strategies can impair
      functional recovery after TKA. Moreover, unlike previous work, the principal
      endpoint of our study is an objective measurement of walking capacity, and not a
      questionnaire. CLINICAL REHABILITATION IMPACT: WE suggest that programs aimed at
      the management of such cognitive and behavioral factors which contribute to
      activity avoidance during rehabilitation are likely to improve functional
      recovery after TKA.

PMID- 25392088
TI  - Complete nucleotide sequence of Klebsiella phage P13 and prediction of an EPS
      depolymerase gene.
AB  - The complete genome of Klebsiella phage P13 was sequenced and analyzed.
      Bacteriophage P13 has a double-stranded linear DNA with a length of 45,976 bp and
      a G+C content of 51.7 %, which is slightly lower than that of Klebsiella
      pneumoniae KCTC 2242. The codon biases of phage P13 are very similar to those of
      SP6-like phages and K. pneumoniae KCTC 2242. Bioinformatics analysis shows that
      the phage P13 genome has 282 open reading frames (ORFs) that are greater than 100
      bp in length, and 50 of these ORFs were identified as predicted genes with an
      average length of 833 bp. Among these genes, 41 show homology to known proteins
      in the GenBank database. The functions of the 24 putative proteins were
      investigated, and 13 of these were found to be highly conserved. According to the
      homology analysis of the 50 predicted genes and the whole genome, phage P13 is
      homologous to SP6-like phages. Furthermore, the morphological characteristics of
      phage P13 suggest that it belongs to the SP6-like viral genus of the Podoviridae
      subfamily Autographivirinae. Two hypothetical genes encoding an extracellular
      polysaccharide depolymerase were predicted using PSI-BLAST. This analysis serves
      as groundwork for further research and application of the enzyme.

PMID- 25392089
TI  - Recombination analysis of Maize dwarf mosaic virus (MDMV) in the Sugarcane mosaic
      virus (SCMV) subgroup of potyviruses.
AB  - Recombination among RNA viruses is a natural phenomenon that appears to have
      played a significant role in the species development and the evolution of many
      strains. It also has particular significance for the risk assessment of plants
      which have been genetically modified for disease resistance by incorporating
      viral sequences into their genomes. However, the exact recombination events
      taking place in viral genomes are not investigated in detail for many virus
      groups. In this analysis, different single-stranded positive-sense RNA
      potyviruses were compared using various in silico recombination detection methods
      and new recombination events in the Sugarcane mosaic virus (SCMV) subgroup were
      detected. For an extended in silico recombination analysis, two of the analyzed
      Maize dwarf mosaic virus full-length genomes were sequenced additionally during
      this work. These results strengthen the evidence that recombination is a major
      driving force in virus evolution, and the emergence of new virus variants in the
      SCMV subgroup, paired with mutations, could generate viruses with altered
      biological properties. The intra- and interspecific homolog recombinations seem
      to be a general trait in this virus group, causing little or no changes to the
      amino acid of the progenies. However, we found a few breakpoints between the
      members of SCMV subgroup and the weed-infecting distant relatives, but only a few
      methods of the RDP3 package predicted these events with low significance level. 

PMID- 25392091
TI  - Retraction: Association between bevacizumab-related chemotherapy regimens and
      serum vascular endothelial growth factor-A165b level in patients with metastatic
      colorectal cancer.
AB  - The article "Association between bevacizumab-related chemotherapy regimens and
      serum vascular endothelial growth factor-A165b level in patients with metastatic
      colorectal cancer" by L. Xu, C. Chi, C. Wang, L.M. Zhang, published in Eur Rev
      Med Pharmacol Sci 2014;  18 (18): 2687-2692 has been withdrawn. 

PMID- 25392090
TI  - [Mirror therapy for the treatment of phantom limb pain after bilateral thigh
      amputation. A case report].
AB  - This case study is the first to report successful treatment of bilateral phantom
      limb pain (PLP) in a patient with bilateral thigh amputation and inefficacious
      medical treatment using a protocol of graded interventions including mirror
      therapy (MT). MT is a common treatment for PLP but requires the induction of a
      visual illusion of an intact limb in the mirror, usually achieved by mirroring
      the healthy extremity. Here, we illustrate how application of a unilateral
      prosthesis sufficed to induce the necessary illusion. After sequential imagery,
      then lateralization training, which alleviated pain attacks, the patient received
      a further 3-week treatment of mirror treatment. Pain intensity was reduced by
      more than 85 %; the number of attacks were decreased by more than 90% per day.
      The analgesic efficacy lasted until the unexpected death of the patient several
      months later. This case illustrates the mechanisms of MT through overcoming the
      sensory incongruences underlying the distorted body schema and its efficacy in
      patients with bilateral amputation. 

PMID- 25392092
TI  - Static and dynamic MR imaging in the evaluation of temporomandibular disorders.
AB  - OBJECTIVE: The aim of this study is to prove if dynamic HASTE (half-Fourier
      acquisition single-shot turbo spin-echo) sequences can be used in the diagnosis
      of internal derangement disorders of temporomandibular joint (TMJ) as an
      alternative to static proton density (PD) weighted/turbo spin echo (TSE) T2
      weighted sequences which are considered up to now as the gold standard in the
      evaluation of TMJ disorders (TMDs). PATIENTS AND METHODS: 194 patients for a
      total of 388 TMJs were examined with a 1.5 Tesla field strength superconducting
      magnet. Sagittal static PD-weighted/TSE T2-weighted and dynamic HASTE sequences
      have been used. Three experts in the field of oral radiology (specialist A, B and
      C) independently and blinded to clinical symptoms and any treatment, assessed the
      articular disc position in each TMJ (rated as normal or disc displacement with
      reduction or disc displacement without reduction). The agreement between static
      and dynamic images and between the three different specialists in the assessment
      of the articular disc position was evaluated using kappa statistic. RESULTS: The
      agreement between static and dynamic images is: for specialist A, K = 0.862; for
      specialist B, K = 0.870 and for specialist C, K = 0.862. CONCLUSIONS: Since there
      is no complete agreement between these two MR techniques, dynamic sequences can
      not be used as a reliable alternative to static sequences in the evaluation of
      internal derangement disorders of TMJ.

PMID- 25392093
TI  - Kinematic viscosity of unstimulated whole saliva in healthy young adults.
AB  - OBJECTIVE: To analyze kinematic viscosity and pH of unstimulated whole saliva,
      evaluate possible variations after sampling, identify any gender differences and
      detect possible correlations between them. SUBJECTS AND METHODS: The sample
      consisted of sixty-four healthy young adults (37 females and 27 males, mean age
      25.2 years). Saliva was collected using the spitting method at 11:00 am.
      Kinematic viscosity was determined with a capillary viscometer (ViscoClock,
      Schott-Gerate Mainz, Germany) equipped with a micro-Ubbelohde capillary.
      Viscosity and pH were measured at a temperature of 36  degrees C in a
      thermostatic bath. Viscosity and pH data were evaluated almost simultaneously at
      six different times after sampling in order to identify any variations due to
      aging. The data were statistically analyzed using Student's t test and Wilcoxon
      Mann-Whitney test. RESULTS: In total sample kinematic viscosity was 1.40 cSt (SD
      = 0.39; RSD % = 27.81), in the male and female groups was 1.33 cSt (SD = 0.35,
      RSD% = 26.31) and 1.45 cSt (SD = 0.41, RSD % = 28.45) respectively; the
      difference was not statistically significant. Viscosity decreased exponentially
      as a function of time after sampling then reaching a plateau around 1.12 cSt,
      while the pH values increased linearly. There was a trend of pH to decrease while
      viscosity decreases. CONCLUSIONS: Kinematic viscometry could be a valid tool to
      evaluate salivary viscosity. Degradation of saliva after sampling affects
      viscosity and slightly pH. The use of capillary viscometer to evaluate salivary
      aging needs more improvements. Further studies are required to investigate and
      explain the effects of different techniques to reduce the film forming on the
      air/liquid interface during measurement.

PMID- 25392094
TI  - The results of national newborn hearing screening (NNHS) data of 11,575 newborns
      from west part of Turkey.
AB  - OBJECTIVE: In this study, we aimed to review the National Newborn Hearing
      Screening (NNHS) programme data obtained from Corlu, located in west part of
      Turkey for the last 4 years. SUBJECTS AND METHODS: A total 11575 newborns that
      were either born in Corlu State Hospital or referred from other Health Care
      Centers, between September 2009 and November 2012 were included into the study.
      Automated-Transient Evoked Otoacoustic Emission (A-TEOAE) test and Automated
      Auditory Brainstem Response (A-ABR) were used as screening tests. When the
      newborn had failed at the initial A-TEOAE test, then the test was repeated after
      15 days. If the same result was obtained at the second test; the newborns were
      referred for ENT examination. A-TEOAE and A-ABR screening tests were performed as
      the third stage evaluation. The failed newborns were referred for clinical ABR
      test. RESULTS: Out of 11575 newborns, 593 (5.12%) had failed the test and they
      were referred for clinical ABR. Out of these 593 neonates, 470 had passed the
      diagnostic ABR test at the referral center. Bilateral and unilateral sensori
      neural hearing loss (SNHL) was detected at 15 and 7 babies respectively, 10 of 22
      of these babies had risk factors such as family history of hearing loss, and
      parental consanguinity. CONCLUSIONS: The final hearing impairment and risk factor
      rates of our study was similar with literature. Although referral rates and the
      number of default babies gradually decreased in the last 4 years; definitive
      diagnosis and hearing aid initiation times need to improvement.

PMID- 25392095
TI  - Osteogenesis of umbilical mesenchymal stem cells is enhanced in absence of DNA
      methyltransferase 3B (DNMT3B) through upregulating Runx2 expression.
AB  - OBJECTIVE: Umbilical mesenchymal stem cells (UMSCs) is one of most popular
      regenerative medical source of bone replacement therapy in both clinical and
      scientific researches. However, it is still low effective to induce the
      osteogenesis of hUMSCs. In this study, we aimed to elucidate the roles of DNA
      methyltransferase 3B (DNMT3B) in the osteogenesis of hUMSCs. MATERIALS AND
      METHODS: Knockdown DNMT3B in hUMSCs was gained via RNA interference technology.
      After confirming the decrease of DNMT3B in mutant hUMSCs by immunostaining and
      qPCR, osteogenesis differentiation was carried out. To identify the phenotype of
      osteogenesis in both bone formation ability and function of bone, immunostaining,
      qPCR and functional test was performed, compared to wildtype hUMSCs. RESULTS:
      Real-time Quantitative PCR (qPCR) and immunostaining results indicated that
      lacking of DNTM3B the osteogenesis related genes were significantly
      downregulated. Meanwhile, the functional test was also consistent with the
      downregulated differentiation result. CONCLUSIONS: The osteogenesis
      differentiation of hUMSCs is impaired in the absence of DNMT3B.

PMID- 25392096
TI  - In contrast to leptin, serum concentrations of ghrelin are not related to
      premenstrual syndrome.
AB  - OBJECTIVE: Premenstrual syndrome (PMS) is a disorder related to mood and appetite
      changes during the premenstrual phase. Unfortunately, the understanding of the
      pathophysiology of PMS is quite poor. Though, ghrelin and leptin play important
      roles in the control of food intake. The aim of this study was to evaluate leptin
      and ghrelin serum concentrations in PMS patients. PATIENTS AND METHODS: Forty
      five PMS patients diagnosed according to ICD-10 diagnostic criteria and 45
      healthy women as a control group, were included in the study. These groups were
      matched for age, body mass index and duration of menstrual cycle. Symptoms of the
      patients were evaluated using "Menstrual Distress Questionnaires". Serum leptin
      and ghrelin serum concentrations were measured using ELISA in the postmenstrual
      phase (5-9 days) and 2-3 days before menstruation. Mann-Whitney U test,
      independent sample t-test and Wilcoxon test were used for statistical analyses.
      RESULTS: In the PMS group, there was no difference in the serum concentrations of
      ghrelin; however, leptin serum concentrations were 31.05 (+/- 14.16) and 16.42
      (+/- 15.81) ng/ml during the premenstrual and postmenstrual periods, respectively
      (p < 0.05). Ghrelin serum concentrations in the premenstrual period were 6.9 (+/-
      9.3) ng/ml in the PMS group and 8.8 (+/- 9.3) ng/ml in the control group, but
      this difference was not statistically significant (p = 0.79). CONCLUSIONS:
      Ghrelin serum concentrations were not associated with PMS, while leptin serum
      concentrations were found to be higher in the premenstrual period in PMS
      patients. Though, these two hormones work antagonistically to control the food
      intake and body weight, we suggest that this function is not relevant to PMS.

PMID- 25392097
TI  - Relationship between meconium staining and thymic stromal lymphopoietin.
AB  - OBJECTIVE: Epithelium-derived thymic stromal lymphopoietin (TSLP), is a key pro
      allergic cytokine that has recently been linked to chronic airway diseases. Our
      aim is to determine cord blood TSLP levels in pregnancies with meconium stained
      amniotic fluid. PATIENTS AND METHODS: A total of 44 pregnant women with meconium
      stained amniotic fluid and a total of 44 healthy pregnant women were enrolled in
      the study. Cord blood TSLP was measured with TSLP ELISA Kit. RESULTS: We found no
      statistically significant differences between 2 groups in terms of age and
      parity. TSLP levels were found to be significantly higher in the cord blood of
      pregnant women with meconium stained amniotic fluid (104.3 +/- 96.9 ng/ml)
      compared with the control group (63.2 +/- 65.3 ng/ml) (p = 0.022). CONCLUSIONS:
      It seems that TSLP is produced and released in response to meconium.

PMID- 25392098
TI  - Pregnancy outcome and obstetric management after vaginal radical trachelectomy.
AB  - OBJECTIVE: Radical vaginal trachelectomy (VRT) is widely prescribed as a surgical
      procedure to treat early-stage cervical cancer while preserving fertility.
      However, the ideal obstetric standard of care for patients who have undergone VRT
      has not yet been established. Aim of this rerport is to analyze pregnancy
      outcomes and optimal obstetric management during pregnancy and delivery after
      vaginal radical trachelectomy (VRT). PATIENTS AND METHODS: Forty-six cases of VRT
      from December 2003 to April 2013 in Peking Union Medical College Hospital were
      analyzed. RESULTS: The mean age of the patients at the time of VRT was 30.6 years
      and the mean follow-up time was 39.5 months. Of the 32 patients who attempted to
      conceive, 12 had 16 successful conceptions. There were two miscarriages and two
      elective abortions. One case of ectopic pregnancy and one case of second
      trimester loss occurred in this cohort. Ten cases reached the third trimester.
      Two patients delivered before 32 weeks, and four before 37 weeks. The total
      preterm delivery rate was 60%. All ten patients delivered by Cesarean section
      through a high transverse uterine incision. No uterine rupture or postpartum
      hemorrhage occurred. CONCLUSIONS: There is an increased occurrence of preterm
      delivery after VRT. Cesarean section after full term pregnancy through a high
      transverse incision should be considered as a suitable and safe procedure.

PMID- 25392099
TI  - Mini mental state exam versus Montreal cognitive assessment in patients with age
      related macular degeneration.
AB  - OBJECTIVE: To compare the ability of the MMSE and MoCA to identify cognitive
      dysfunction in patients with age-related macular degeneration (AMD). PATIENTS AND
      METHODS: The study included 81 (29 female, 52 male) AMD patients who were
      recruited from the Ophthalmology Department of Kirikkale University during 2012.
      Participants were screened for cognitive impairment using the MMSE and MoCA. The
      scores were recorded for all participants. The primary outcome measure was the
      proportion of patients with a score less than 21 on either test. RESULTS: The
      percentage of subjects who scored below a cut off of 21/30 was higher on the MoCA
      (48.1%) than on the MMSE (18.5%) (p = 0.05). The range and standard deviation of
      scores was larger with the MoCA (7-30, 5.34) than with the MMSE (19-30, 3.26).
      There was a more pronounced ceiling effect of the MMSE than of the MoCA. The mean
      MMSE scores of dry-and wet-type AMD patients was significantly higher than the
      MoCA scores of the same patients (p = 0.000 and p = 0.000). CONCLUSIONS: The MoCA
      seems to be more sensitive than the MMSE to early cognitive impairment in AMD
      patients.

PMID- 25392100
TI  - Dynamic changes of the various cytokines following carotid artery stenting.
AB  - OBJECTIVE: To observe the serum inflammatory and coagulation factors changes and
      clinical significance following carotid artery stenting. PATIENTS AND METHODS:
      The expressions of serum inflammatory factors including IL-2, IL-6, IL-8, sICAM
      1, hs-CRP, and TNF-alpha and serum coagulation factors including prothrombin time
      (PT), active partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (DD),
      and fibrin degradation products (FDP) were determined in 92 patients who had
      undergone carotid artery stenting before, 24h, 48 h, 3 days and 1 week after the
      surgery. As well, 92 subjects who did not receive stenting were enrolled in the
      angiography group, amongst whom the same variables were determined. RESULTS: In
      the stenting group, the expressions of hs-CRP, TNF-alpha, sICAM-1, IL-6, IL-8,
      FIB, and DD were significantly increased after the surgery (p < 0.05): hs-CRP
      reached a peak 48 h after the surgery; TNF-alpha, sICAM-1, and IL-6 maintained at
      high levels at days 3-7; and FIB and DD increased 48 h and 3d after the surgery.
      Compared with the angiography group, the expressions of hs-CRP, TNF-alpha, sICAM
      1, and IL-8 (24h after the surgery) as well as FIB and DD (48 h and 3d after the
      surgery) were significantly higher in the stenting group. CONCLUSIONS: The hs
      CRP, TNF-alpha, sICAM-1, IL-8, FIB, and DD increased after carotid artery
      stenting and, therefore, can serve as important factors for monitoring for acute
      postoperative complications.

PMID- 25392101
TI  - Artificial pneumothorax in CT-guided radioactive iodine-125 seed implantation in
      the treatment of mediastinal tumors.
AB  - OBJECTIVE: To explore the efficacy and safety of CT-guided radioactive Iodine-125
      seed implantation in treating mediastinal tumors in the thorax with artificial
      pneumothorax. PATIENTS AND METHODS: Artificial pneumothorax was created using the
      22 G thoracic puncture needle in 36 patients with mediastinal tumors, followed by
      CT-guided radioactive Iodine-125 seed implantation. An equal volume of gas was
      extracted after the treatment. RESULTS: The treatment was completed in 35
      patients. The tumor target volumes for the radiation treatment were not
      significantly different before and after the artificial pneumothorax (p = 0.265).
      No severe complications such as refractory pneumothorax, hemoptysis, or diffuse
      hemorrhage in the implantation area was observed. CONCLUSIONS: Artificial
      pneumothorax can reduce the CT image interference caused by the needle tract
      bleeding during the radioactive Iodine-125 implantation.

PMID- 25392102
TI  - IMPDH2 mediate radioresistance and chemoresistance in osteosarcoma cells.
AB  - OBJECTIVE: Osteosarcoma (OS) is the most common primary malignant bone tumour in
      children and adolescents. Despite aggressive therapy, survival outcomes remain
      unsatisfactory, especially for patients with metastatic disease or patients with
      a poor chemotherapy response. Previous study founds inosine 5'-monophosphate
      dehydrogenase type II (IMPDH2) was an independent prognostic factor and observed
      frequent IMPDH2 overexpression in osteosarcoma patients with poor response to
      chemotherapy. In the present work, we provide evidence for direct involvement of
      IMPDH2 in the development of radioresistance and chemoresistance. MATERIALS AND
      METHODS: The expression of IMPDH2 was examined in OS cells. Stable cell lines
      overexpressing IMPDH2 and IMPDH2 knock-down cells were generated using the
      osteosarcoma cell line. The stable transfected cells, alone or in combination
      with cisplatin or gamma-irradiation, was used to treat OS cells. The growth
      inhibitory and apoptotic effects of IMPDH2 in vitro and in vivo were examined.
      RESULTS: Overexpression of IMPDH2 in IMPDH2 poor-expressed U2OS cells induced
      strong cisplatin chemoresistance and gamma-irradiation radioresistance through
      inhibition of apoptosis in vitro and in vivo. Knockdown of IMPDH2 in IMPDH2 rich
      expressed Saos-2 cells resulted in significant chemosensitivity and gamma
      irradiation radiosensitivity through inducing of apoptosis in vitro and in vivo.
      CONCLUSIONS: IMPDH2 is directly involved in the development of chemoresistance
      and radioresistance in osteosarcoma cells, suggesting that targeting of IMPDH2 by
      shRNA in combination with chemotherapy and gamma-irradiation might be a promising
      means of overcoming chemoresistance and radioresistance in osteosarcomas with
      high IMPDH2 expression.

PMID- 25392103
TI  - Surgical strategies for unexpected gallbladder carcinoma.
AB  - OBJECTIVE: To explore surgical strategies for unexpected gallbladder carcinoma
      (UGC). PATIENTS AND METHODS: A study of hospital records was performed in 26
      patients with UGC treated in our institution from January 1990 to December 2002.
      The surgical therapies and disease prognosis were analyzed. RESULTS: Five cases
      of GBC were noted during open cholecystectomy (OC) and 15 were confirmed during
      minicholecystectomy (MC), while were 6 identified during laparoscopic (LC)
      surgery; all patients with Nevin Stage I gallbladder carcinoma (GBC) survived > 3
      years; patients with Stage III GBC died within 2 years and patients with Stage IV
      GBC died within 1 year. CONCLUSIONS: Caution must be taken when high risk
      conditions and atypical ultrasonography of gallbladder are encountered.
      Examination of frozen sections should be performed routinely in all cases to
      reduce the rates of misdiagnosis. Surgery is an effective treatment for GBC.

PMID- 25392104
TI  - The use of targeted percutaneous laser disc decompression under the guidance of
      puncture-radiating pain leads to better short-term responses in lumbar disc
      herniation.
AB  - OBJECTIVE: Traditional percutaneous laser disc decompression (PLDD) eliminates
      nucleus pulposus in the center of lumbar discs. Targeted PLDD is an alternative
      technique that involves elimination and decompression of the target area located
      5-8 mm in the front of the herniated disc. We aimed to compare the efficacy of
      targeted PLDD with traditional PLDD in the treatment of lumbar disc herniation
      and evaluate the usefulness of guidance by puncture-radiating pain on clinical
      outcomes of PLDD. PATIENTS AND METHODS: We treated 61 patients with lumbar disc
      herniation. Patients were stratified into control group, which included patients
      who underwent traditional PLDD, and study group in patients underwent targeted
      PLDD. Clinical outcomes and efficacies were evaluated at different time points
      using the visual analog scale (VAS) and modified MacNab criteria. RESULTS:
      Patients in the study group demonstrated significantly greater decreases in the
      VAS scores compared with those in control group. These differences were observed
      on Day 3, and 1 and 3 months after the treatment. Further, VAS scores were
      markedly lower in the patients whose treatment was guided by the puncture
      radiating pain. Thus, at 1 month after the operation, 64.1% of those patients
      showed excellent or good outcomes based on MacNab criteria, which was almost
      twice the percentage seen in patients who did not experience the puncture
      radiating pain (36.4%). CONCLUSIONS: Targeted PLDD is an effective, minimally
      invasive, and safe technique for lumbar disc herniation, and this technique
      achieves better short-term postsurgical outcomes than traditional PLDD. Puncture
      radiating pain is an important prognostic indicator for better short-term
      responses to the treatment.

PMID- 25392105
TI  - Exploring the osteoarthritis-related genes by gene expression analysis.
AB  - OBJECTIVE: Osteoarthritis (OA) is a most common chronic degenerative joint
      lesion, which affects both cartilage and bone. A better understanding of the gene
      expression profiling of OA may help understanding the pathogenesis of OA and
      finding the therapy targets for OA treatment. MATERIALS AND METHODS: GSE8077 was
      downloaded from Gene Expression Omnibus (GEO) including 5 OA rats induced by
      anterior cruciate ligament transection and partial medial meniscectomy and 5 rats
      that were performed sham surgery as control. Differentially expressed genes
      (DEGs) between OA group and control group were identified by t-test with p < 0.05
      and the coding genes that transcription factors corresponded were screened by
      TRANSFAC. Then Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathway enrichment analysis for DEGs and transcription factors were
      performed. The DEGs and transcription factors were integrated with information
      from STRING database to construct PPI network. RESULTS: A total of 119 up
      regulated genes, 39 down-regulated genes and 9 transcription factors were
      identified in OA sample. The GO enrichment analysis showed that 119 up-regulated
      genes were significantly enriched in blood vessel development and KEGG pathway
      enrichment showed that genes were involved in circadian rhythm pathway. In the
      PPI network, Cd44, Mmp13, Timp1 and Igf1 showed higher degrees. CONCLUSIONS: The
      screened genes could provide a new and comprehensive view for treatment of OA.

PMID- 25392106
TI  - Clinical significance of serum survivin in patients with pancreatic ductal
      adenocarcinoma.
AB  - OBJECTIVE: We investigate the clinical significance of survivin levels in
      pancreatic ductal adenocarcinoma (PDAC) patients. PATIENTS AND METHODS: The serum
      level of survivin from patients with PDAC (n = 80) and age-matched healthy
      volunteers (n = 80) were analyzed by enzyme-linked immunosorbent assays (ELISA)
      prior to surgical resection. Expression levels were correlated with
      clinicopathological parameters. RESULTS: Serum survivin concentrations were
      significantly elevated in PDAC patients when compared to healthy sera (p =
      0.001). High serum survivin levels were significantly associated with perineural
      invasion, venous invasion, lymph node status (N stage), histologic grade and T
      stage, but not with the tumor size, age, gender of the patients or tumor
      location. The median overall survival of the normal serum survivin group was
      longer than that of the elevated serum survivin group. The independent factors
      associated with overall survival were advanced pancreatic cancer and elevated
      serum survivin level. CONCLUSIONS: Patients with elevated serum survivin level at
      diagnosis demonstrated poor overall survival. Pretreatment survivin level may
      predict the prognosis of patients with PDAC.

PMID- 25392107
TI  - Hypertonic saline activates CD4+ and CD8+ T-lymphocytes in the small intestine to
      alleviate intestinal ischemia-reperfusion injury.
AB  - OBJECTIVE: Intestinal ischemia-reperfusion injury (I/R) is a common syndrome
      encountered in clinic following intestinal surgery, strangulated hernia, and
      shock. Hypertonic saline has been shown to prevent inflammatory tissue damages
      caused by I/R and regulate immunologic disorders in peripheral blood. However,
      the immunoregulatory effects of hypertonic saline on the small intestine response
      to intestinal I/R have not been reported. MATERIALS AND METHODS: To investigate
      this, we created the intestinal I/R model by clamping the superior mesenteric
      artery in Sprague-Dawley rats. After 1 hour of ischemia, the vascular clamp was
      removed, and either normal saline (0.9% NaCl, NS group) or hypertonic saline
      (7.5% NaCl, HS group) was administered through the tail vein (6 ml/kg). The
      CD4(+) and CD(8+), primarily T-lymphocytes subpopulation yielded from the
      intestinal tissues, were determined by immunohistochemistry. RESULTS: A pro
      inflammatory cytokine, tumor necrosis factor (TNF)-alpha, and nuclear factor
      kappa B (NF-kappaB), a critical transcription factor for the TNF-alpha gene, were
      measured in the intestinal and lung tissues with ELISA. HS induced an increase in
      CD4(+) and CD8(+) T cells in the jejunum and ileum compared with the NS group.
      The levels of TNF-alpha and NF-kappaB in the intestinal and lung tissues were
      significantly decreased in the HS group compared with those of the NS group.
      CONCLUSIONS: HS treatment may ameliorate the tissue damage induced by intestinal
      I/R. This protective effect is possibly due to its ability to activate the CD4(+)
      and CD8(+) T-lymphocytes cells in the intestinal tissues and inhibit the
      intestinal I/R-induced expression of pro-inflammatory cytokines.

PMID- 25392108
TI  - Gastrointestinal stromal tumors: current translational research and management
      modalities.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
      of the gastrointestinal tract. In recent years, detection of these subepithelial
      lesions has improved due to advances in endoscopic imaging techniques.
      Furthermore, developments in immunohistochemical technologies, allowing for
      reliable differentiation of GISTs from other subepithelial tumors, have improved
      the understanding of these lesions significantly. Alongside the emergence of
      these new technologies, clinical management of GISTs has progressed greatly in
      the last decade. However, major controversies still exist in various aspects of
      GIST management, such as diagnosis, treatment, and prognosis. This review article
      provides the current overview of the research status in the management of GISTs. 

PMID- 25392109
TI  - Omega-3 fatty acids: a novel resort against gastrointestinal injury.
AB  - The integrity of gastric barrier derives from the balance between defending and
      damaging factors. In particular, prostaglandins play a relevant role in the
      maintenance of gastric homeostasis and prevention of peptic disease, at different
      levels. Omega-3 fatty acids, particularly eicosapentanoic acid, are the
      precursors of the third series of prostaglandins (with anti-inflammatory
      properties), also reducing the formation of the second series of prostaglandins
      (pro-inflammatory ones). Such a pathophysiological rationale brought to the
      experimental application, both in animal models and, more recently, in humans, of
      omega-3 fatty acids against gastrointestinal damage. Omega-3 fatty acids have
      shown interesting results in preventing different types of gastric damage in
      mouse models. A large retrospective case-control study on patients taking both
      anti-thrombotic therapy and eicosapentanoic acid showed (although only at
      unadjusted analysis) an inverse correlation between consumption of
      eicosapentanoic acid and gastrointestinal injury. Prospective, well-designed,
      comparative studies are warranted to clarify if omega-3 fatty acids may
      represent, or not, a novel resort against gastrointestinal injury. 

PMID- 25392110
TI  - Cardiovascular diseases: oxidative damage and antioxidant protection.
AB  - Atherosclerosis, the hardening of arteries under oxidative stress is related to
      oxidative changes of low density lipoproteins (LDL). The antioxidants prevent the
      formation of oxidized LDL during atherogenesis. Perhaps more than one mechanism
      is involved in the atherosclerosis disease where LDL is oxidized in all the cells
      of arterial wall during the development of this disease. The oxidation of LDL
      produces lipid peroxidation products such as isoprostans from arachidonic,
      eicosapentaenoic and docosahexaenoic acids, oxysterols from cholesterol, hydroxyl
      fatty acids, lipid peroxides and aldehydes. The lipid peroxidation bioassay can
      serve as a marker for the risk of cardiovascular. An in vivo test of levels of
      oxidative lipid damage is an early prediction of development of cardiovascular
      disease (CVD). Serum paraoxonase (PON) activity is correlated to severity of the
      coronary artery disease. The antioxidants level in the serum and serum
      paraoxonase activity provides information for the risk of CVD. The antioxidant
      enzyme superoxide dismutase is responsible for dismutation of superoxide, a free
      radical chain initiator. The subcellular changes in the equilibrium in favor of
      free radicals can cause increase in the oxidative stress which leads to
      cardiomyopathy, heart attack or cardiac dysfunction. The oxidative damage and
      defense of heart disease has been reported where dietary antioxidants protect the
      free radical damage to DNA, proteins and lipids. The ascorbic acid, vitamin C is
      an effective antioxidant and high vitamin E intake can reduce the risk of
      coronary heart disease (CHD) by inhibition of atherogenic forms of oxidized LDL.
      The vitamin A and beta-carotene protect lipid peroxidation and provitamin-A
      activity. It has been recently suggested that the protection of oxidative damage
      and related CVD is best served by antioxidants found in the fruits and
      vegetables. The oxidative damage and antioxidant protection of CVD have been
      described here. 

PMID- 25392111
TI  - Impact of epigenetics in the management of cardiovascular disease: a review.
AB  - Cardiovascular disease (CVD) is the leading cause of death, irrespective of
      socioeconomic status, ethnic background and sex. Despite the considerable
      progress in the treatment, the complex pathophysiology underlying CVD is still
      not clear. In past few years, genetic approaches including epigenetics and
      personalized medicine initiated a new way of treating CVD. Epigenetics refers to
      the non-DNA sequence related heritable changes in gene expression and its role in
      understanding and treating coronary artery disease, heart failure, and cardiac
      hypertrophy is currently recognized as an important player. Histone acetylation,
      deactylation, DNA methylation and histone methylation are different mechanisms of
      epigenetic modifications. Cardiac Hypertrophy is linked with histone acetylation
      and the activity of histone acetyltransferases (HATs) has a positive role in
      cardiac hypertrophy. Altered DNA methylation, miRNA activity have been shown to
      be associated with atherosclerosis. It is documented that re-expression of
      certain fetal genes in the adult heart contributes to the development of heart
      failure syndrome, which is often associated with pathological cardiac remodeling
      comprising of changes in heart mass, size and shape. Thus, it appears that
      approaches that counteract epigenetic changes occurring in CVD can prove to have
      significant therapeutic impact. However, there are no major clinical practice or
      therapeutics reports of epigenetics contribution in CVD, even though deacetylase
      inhibitors like trichostatin A were shown to have some positive effects. In this
      review we will present an overview of various epigenetic mechanisms such as DNA
      methylation, histone modifications, and microRNA-dependent mechanisms in CVD and
      the novel epigenetics-based therapeutic approaches. 

PMID- 25392112
TI  - 2D speckle tracking imaging to assess sepsis induced early systolic myocardial
      dysfunction and its underlying mechanisms.
AB  - OBJECTIVE: The aim of this study was to apply speckle tracking imaging (STI) to
      evaluate rabbit sepsis induced myocardial injury. MATERIALS AND METHODS: Rabbits
      were injected with the endotoxin lipopolysaccharide (LPS). before and 2h, 4h, 6h,
      8h, 12h after the injection of LPS, conventional echocardiography and STI were
      performed to measure left ventricular end diastolic diameter (LVDd), end-systolic
      diameter (LVDs), cardiac output (CO), left ventricular ejection fraction (EF),
      fractional shortening (FS), left ventricular global longitudinal strain (GLS)/GLS
      rate (GLSr), global circumferential strain/strain rate (GCS/GCSr), and the global
      radial strain/strain rate (GRS/GRSr). We also observed the injury with optical
      microscopy. Serum troponin cTnT and TUNEL assays determining myocardial apoptosis
      were also carried out to determine the induced injury levels. RESULTS: None of
      the indicators measured are statistically different in the two groups before the
      LPS treatment (p > 0.05). 2h after LPS injection, in LPS treated group, only
      GLS/GLSr, GCS/GCSr significantly reduced compared to the control group (p <
      0.05). 6h, 8h, 12h after LPS injection, EF and FS were lower (p < 0.05), LVDd and
      LVDs were higher (p < 0.05), and GLS/GLSr, GCS/GCSr, GRS/GRSr were significantly
      lower (p < 0.05). LPS significantly elevated serum cTnT level in the experimental
      group (p < 0.05). In the LPS treated group, we found pathological changes of the
      myocardium. CONCLUSIONS: STI is more sensitive than the conventional
      echocardiography for the early detection of abnormal myocardial contractility. It
      is a noninvasive, accurate and timely detection of myocardial dysfunction in
      sepsis.

PMID- 25392113
TI  - Ventricular fibrillation induction and diffuse abnormal ST-segment response to
      ajmaline in a patient with apparent pre-existing dynamic right bundle branch
      block.
AB  - OBJECTIVE: ST-segment elevation in the right precordial electrocardiography (ECG)
      leads in Brugada syndrome (BS) can be unmasked by class I anti-arrhythmic drugs
      (sodium channel blockers) administration. It is still debated whether this ECG
      pattern is better explained by abnormal repolarization or ventricular conduction
      and depolarization. Conduction diseases can conceal type 1 BS-like ECG in
      standard V1-V3 leads. ECG alterations were found also in alternative leads. The
      role of electrophysiology study (EPS) in sudden cardiac death risk stratification
      remains controversial, and could depend on the phenotypic expression of the
      cardiac sodium channels disease. CASE REPORT: We describe unmasked diffuse J
      point and ST-segment anomalies in peripheral and precordial ECG leads and
      ventricular fibrillation (VF) induction by EPS after ajmaline administration in a
      patient with pre-existing atypical right bundle branch block (RBBB) concealing
      subtle anomalies in standard V1-V3 leads. RBBB was influenced by the underlying
      BS-like ECG associating repolarization anomaly and pre-existing conduction
      disease. EPS induced VF when RBBB was associated with BS-like ECG, and failed to
      induce VF when RBBB was present alone. CONCLUSIONS: BS phenotype heterogeneity
      requires further studies to improve the knowledge of its pathophysiological
      mechanisms associated with conduction diseases in order to better identify an
      individual therapy and prognostic stratification.

PMID- 25392114
TI  - Beanblock(r) (standardized dry extract of Phaseolus vulgaris) in mildly
      overweight subjects: a pilot study.
AB  - OBJECTIVE: This study evaluates the efficacy of Beanblock(r), a standardized
      extract of Phaseolus vulgaris L., on weight control in healthy overweight
      subjects on a weight management plan that combined lifestyle and dietary advice.
      PATIENTS AND METHODS: Sixty overweight (BMI 25-30 kg/m2) healthy subjects were
      enroled. All subjects were instructed to follow a weight management plan,
      accompanied by dietary advice. Thirty subjects used Beanblock(r) for at least 12
      weeks (50 mg tablets, two times daily). The remaining 30 subjects did not receive
      any supplementation (management-only). The main endpoints were changes in body
      weight and waist circumference, with plasmatic oxidative stress, satiey and
      appetite being also evaluated. RESULTS: At week 12, the supplementation with
      Beanblock(r) was associated with a reduction in body weight (from 82.8 +/- 9.1 kg
      to 78.8 +/- 8.9 kg; p < 0.0001) and a decrease of waist circumference from 94.4
      +/- 10.3 cm to 88.2 +/- 10.0 cm (p < 0.0001). Conversely, only marginal changes
      were observed in the control group. Oxidative stress was also significantly
      decreased with Beanblock(r) (from 380.4 +/- 14.8 to 340.7 +/- 14.8 Carr Units; p
      < 0.0001). Satiety and appetite improved in the supplement group. No side effects
      were observed and compliance was optimal. CONCLUSIONS: Beanblock(r), in
      association with a health management plan, was useful for weight control in
      mildly overweight healthy subjects.

PMID- 25392115
TI  - The pharmacokinetics of oral oxycodone in patients after total gastric resection.
AB  - OBJECTIVE: Oxycodone is a semi-synthetic opioid with a stronger analgesic effect
      than morphine and codeine. The efficacy of this opioid in the treatment of
      postoperative pain has been proved in different groups of patients. The drug has
      a favourable adverse reaction profile, which encourages doctors and patients to
      use it more and more widely. The drug is also used in the patients who underwent
      an abdominal surgery, e.g. stomach resection. Gastrectomy leads to
      pathophysiological changes within the gastrointestinal tract, which may cause
      changes in the drug absorption. In consequence this leads to a change in the
      pharmacokinetics and effect of the drug. The aim of the research was an analysis
      of the pharmacokinetics of oxycodone from prolonged release tablet in patients
      after total gastrectomy. PATIENTS AND METHODS: The research was carried out on
      patients after gastrectomy with Roux-en-Y reconstruction. The patients (n=24;
      mean [SD] age, 67.6 [9.8] years; weight, 69.1 [13.6] kg; and BMI, 25.2 [4.0]
      kg/m(2)) received oxycodone in a prolonged release tablet in a single orally
      administered dose of 10 mg. Blood samples were collected within 12 h after the
      drug administration. The plasma concentrations of oxycodone and noroxycodone were
      measured with validated high-pressure liquid chromatography coupled with triple
      tandem mass spectrometery method. RESULTS: The main pharmacokinetic parameters
      for oxycodone in men (n = 14) and women (n = 10) were as follows: Cmax, 14.40
      (3.76) and 11.54 (6.98) ng/ml (p = 0.2066); AUC0-infinity, 157.87 (56.89) and
      106.44 (61.31) ng'h/ml (p = 0.0460); tmax, 2.18 (0.58) and 2.15 (0.58) h (p =
      0.8008), respectively. CONCLUSIONS: Total gastrectomy did not affect the
      pharmacokinetics of oxycodone administered in prolonged release tablets, but the
      exposure to the drug was significantly lower in women.

PMID- 25392116
TI  - Mechanism of curcumin analog MHMD-induced cell death in A549 lung cancer cells.
AB  - OBJECTIVE: To investigate the anticancer properties of a chemosynthetic curcumin
      analog, (1E,6E)-4-((furan-2-yl)methylene)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta
      1,6-diene-3,5-dione (C26H22O7, abbreviated MHMD) in A549 cells. MATERIALS AND
      METHODS: Inverted microscope was used to observe the alteration on
      cytomorphology. MTT assay was used to detect cell viability. Acridine-orange
      staining was used to measure autophagy, and AnnexinV/PI staining and Hoechst/PI
      staining to measure apoptosis and necrosis. RESULTS: MTT assays showed that at 12
      h, 24 h, 48 h, MHMD reduced cell viability with an IC50 of 27.46 uM, 18.86 uM,
      and 11.23 uM, respectively. Typical characteristics were observed in concert with
      cell death, including treated-cells getting brighter, rounder, and becoming non
      adherent gradually. Additionally, acridine-orange staining suggested that
      autophagy didn't involve in MHMD-induced cell death. However, apoptosis and
      necrosis played important roles in MHMD-induced cell death by Hoechst33342/PI
      staining. It showed apoptosis was the main cause at low concentrations (<= 4 uM),
      while with the concentrations rising, necrosis was the leading role. AnnexinV/PI
      staining again indicated the occurrence of apoptosis at 4 uM. Furthermore, the
      caspases inhibitor z-VAD-fmk could prevent MHMD-induced cell death, which showed
      much higher cell viability than those only treated with MHMD (4 uM). Moreover,
      MTT assay also demonstrated that MHMD did possess a greater anti-proliferative
      ability than curcumin. CONCLUSIONS: The curcumin analog MHMD is able to induce
      A549 cell death in a time and dose-dependent manner via apoptosis and necrosis.
      And MHMD could be a more effective drug than curcumin.

PMID- 25392117
TI  - Paracetamol-codeine compared to ketorolac for pain control in the Emergency
      Department.
AB  - OBJECTIVE: Paracetamol /codeine has shown a strong analgesic activity in several
      studies conducted among different kind of subjects, including those with trauma.
      Nevertheless, its efficacy in patients accessing the Emergency Department (ED)
      for different kind of pain has never been tested. PATIENTS AND METHODS: This is a
      cross-sectional, observational, prospective, cohort study. Inclusion criteria
      were patients > 18 year old presenting to the ED for localized traumatic or
      inflammatory pain involving only extremities. Numeric scale (NRS) was recorded
      thirty minutes and two hours after the administration of the analgesic therapy,
      consisting of 15 mg of ketorolac or 1000 mg/60 mg of paracetamol/ codeine, both
      orally. RESULTS: Two-hundred patients were consecutively enrolled; 87 were
      treated with paracetamol/codeine and 113 with ketorolac. The combination
      paracetamol/codeine resulted to be not inferior to ketorolac in non-traumatic
      pain group and trauma group (p = 0.635 and p = 0.482, respectively). Compared to
      ketorolac, the combination paracetamol/codeine exerted a significantly higher
      analgesic activity in patients with fractures and muscular pain (p = 0.044) and
      was more effective in acute pain (p = 0.002), with a significant effect two hours
      after the administration (p = 0.029). CONCLUSIONS: Paracetamol/codeine is
      equivalent to ketorolac in non-traumatic pain and post-traumatic pain, but is
      superior in acute pain and in patients with fractures and muscular pain. Those
      results play in favor of the use of the combination paracetamol/codeine in
      patients accessing the ED for non-traumatic or traumatic pain of the extremities.

PMID- 25392118
TI  - Arthritis patients' motives for (not) wanting to be involved in medical decision
      making and the factors that hinder or promote patient involvement.
AB  - The aim of this study is to gain insight into arthritis patients' motives for
      (not) wanting to be involved in medical decision-making (MDM) and the factors
      that hinder or promote patient involvement. In-depth semi-structured interviews
      were conducted with 29 patients suffering from Rheumatoid Arthritis (RA). Many
      patients perceived the questions about involvement in MDM as difficult, mostly
      because they were unaware of having a choice. Shared decision-making (SDM) was
      generally preferred, but the preferred level of involvement varied between and
      within individuals. Preference regarding involvement may vary according to the
      type of treatment and the severity of the complaints. A considerable group of
      respondents would have liked more participation than they had experienced in the
      past. Perceived barriers could be divided into doctor-related (e.g. a
      paternalistic attitude), patient-related (e.g. lack of knowledge) and context
      related (e.g. too little time to decide) factors. This study demonstrates the
      complexity of predicting patients' preferences regarding involvement in MDM: most
      RA patients prefer SDM, but their preference may vary according to the situation
      they are in and the extent to which they experience barriers in getting more
      involved. Unawareness of having a choice is still a major barrier for patient
      participation. The attending physician seems to have an important role as
      facilitator in enhancing patient participation by raising awareness and offering
      options, but implementing SDM is a shared responsibility; all parties need to be
      involved and educated. 

PMID- 25392119
TI  - Blood management of staged bilateral total knee arthroplasty in a single
      hospitalization period.
AB  - INTRODUCTION: Few literatures have studied the blood management in patients
      treated with staged bilateral primary total knee arthroplasty (TKA) in a single
      hospitalization period. Therefore, this study aims to evaluate the effectiveness
      and safety of the newly introduced multimodal blood management (MBM) in these
      patients. MATERIALS AND METHODS: We retrospectively compared the perioperative
      parameters in 70 cases undergoing staged bilateral primary TKA in a single
      hospitalization period from 2012-2013 in a single center with two different
      groups of patients, allocating cases to the group with the newly introduced MBM
      (Group A, n =33) and controls to the group without the newly introduced MBM
      (Group B, n =37). The newly introduced MBM protocols include preoperative
      hemoglobin (Hb) evaluation, high protein diet, tourniquet release after skin
      closure, preoperative oral iron treatment and femoral canal obturation, and one
      dose of tranexamic acid (TXA) IV with another one if necessary. While in the
      control group, only routine blood-saving techniques were used. RESULTS: Group A
      had a transfusion rate of 9% (3/33), whereas 32.4% of patients (12/37) in Group B
      received allogenic blood transfusion. Significant benefits were also found in
      Group A in terms of postoperative Hb and hematocrit (Hct), reduction of
      postoperative pain, swelling, postoperative pain, length of stays, and hospital
      costs. No deep vein thrombosis (DVT) events were found in all these patients.
      CONCLUSIONS: The newly introduced MBM in staged bilateral TKA in a single
      hospitalization period can reduce blood loss effectively as well as pain and knee
      joint swelling instead of leading to increased complications and result in
      significant cost savings.

PMID- 25392120
TI  - Towards cybernetic surgery: robotic and augmented reality-assisted liver
      segmentectomy.
AB  - BACKGROUND: Augmented reality (AR) in surgery consists in the fusion of synthetic
      computer-generated images (3D virtual model) obtained from medical imaging
      preoperative workup and real-time patient images in order to visualize unapparent
      anatomical details. The 3D model could be used for a preoperative planning of the
      procedure. The potential of AR navigation as a tool to improve safety of the
      surgical dissection is outlined for robotic hepatectomy. MATERIALS AND METHODS:
      Three patients underwent a fully robotic and AR-assisted hepatic segmentectomy.
      The 3D virtual anatomical model was obtained using a thoracoabdominal CT scan
      with a customary software (VR-RENDER(r), IRCAD). The model was then processed
      using a VR-RENDER(r) plug-in application, the Virtual Surgical Planning (VSP(r),
      IRCAD), to delineate surgical resection planes including the elective ligature of
      vascular structures. Deformations associated with pneumoperitoneum were also
      simulated. The virtual model was superimposed to the operative field. A computer
      scientist manually registered virtual and real images using a video mixer (MX 70;
      Panasonic, Secaucus, NJ) in real time. RESULTS: Two totally robotic AR
      segmentectomy V and one segmentectomy VI were performed. AR allowed for the
      precise and safe recognition of all major vascular structures during the
      procedure. Total time required to obtain AR was 8 min (range 6-10 min). Each
      registration (alignment of the vascular anatomy) required a few seconds. Hepatic
      pedicle clamping was never performed. At the end of the procedure, the remnant
      liver was correctly vascularized. Resection margins were negative in all cases.
      The postoperative period was uneventful without perioperative transfusion.
      CONCLUSIONS: AR is a valuable navigation tool which may enhance the ability to
      achieve safe surgical resection during robotic hepatectomy.

PMID- 25392121
TI  - Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by
      human M2 macrophages.
AB  - M2 macrophages suppress inflammation in numerous disorders, including tumour
      formation, infection and obesity. However, the exact role of M2 macrophages in
      the context of several other diseases is still largely undefined. We here show
      that human M2 macrophages promote inflammation instead of suppressing
      inflammation on simultaneous exposure to complexed IgG (c-IgG) and TLR ligands,
      as occurs in the context of diseases such as rheumatoid arthritis (RA). c-IgG-TLR
      ligand co-stimulation of M2 macrophages selectively amplifies production of pro
      inflammatory cytokines TNF-alpha, IL-1beta and IL-6 and promotes Th17 responses,
      which all play a critical role in RA pathology. Induction of pro-inflammatory
      cytokines on c-IgG co-stimulation mainly depends on Fc gamma receptor IIa
      (FcgammaRIIa), which selectively amplifies cytokine gene transcription and
      induces caspase-1 activation. These data indicate that FcgammaR-TLR cross-talk
      may be targeted for treatment to attenuate inflammation in RA, by restoring the
      anti-inflammatory function of M2 macrophages. 

PMID- 25392122
TI  - Retraction Note: Improved treatment of Asthma by using natural sources of
      antioxidants.
AB  - [This retracts the article DOI: 10.1186/2193-1801-2-278.]. 

PMID- 25392123
TI  - Epithelial ovarian cancer - more data, more questions?
AB  - This review provides an overview of latest insights in epithelial ovarian cancer
      biology. The current understanding of the origin and the complex heterogeneity
      are depicted, followed by an introduction to the latest therapeutic approaches.
      The role of the tumor microenvironment, the high potential to disseminate within
      the peritoneal cavity, and new molecular biological findings are summarized. 

PMID- 25392124
TI  - mPEG-b-PCL/TPGS mixed micelles for delivery of resveratrol in overcoming
      resistant breast cancer.
AB  - OBJECTIVE: Drug resistance remains a major challenge for effective breast cancer
      chemotherapy. Resveratrol (Res) is a promising candidate for overcoming cancer
      chemoresistance, but it has low bioavailability due to poor absorption, and ready
      metabolism limits its application. This study aims to develop a Res-loaded mixed
      micelle system to be effective on drug resistance of breast cancer cells.
      METHODS: A mixed micelle system made of methoxy poly (ethylene glycol)-b
      polycaprolactone (mPEG-PCL) and d-alpha-Tocopherol polyethylene glycol succinate
      was prepared and Res was encapsulated to form Res-loaded mixed micelles.
      Furthermore, the antitumor activity against doxorubicin (Dox)-resistant breast
      cancer MCF-7/ADR cells was studied and the possible mechanism was elucidated.
      RESULTS: The mixed micellar formulation increased drug uptake efficiency of Res
      by Dox-resistant breast cancer MCF-7/ADR cells, and induced higher rates of
      apoptotic cell death, as assessed by the accumulation of Sub G1 phases of cell
      cycle, nucleus staining and Annexin-FITC/propidium iodide assay. Moreover, Res
      loaded mixed micelles also markedly enhanced Dox-induced cytotoxicity in MCF
      7/ADR cells and increased the cellular accumulation of Dox by downregulating the
      expression of P-glycoprotein (P-gp) and inhibiting the activity thereof.
      CONCLUSION: The cumulative evidence indicates that Res-loaded mixed micelles hold
      significant promise for the treatment of drug-resistant breast cancer.

PMID- 25392125
TI  - LEVEL OF SOMATIC DEVELOPMENT OF CHILDREN AGED SIX YEARS FROM AN URBAN
      AGGLOMERATION IN POLAND WITH RESPECT TO SELECTED ENVIRONMENTAL CONDITIONS.
AB  - The aim of this study was to assess the somatic development of children from an
      urban agglomeration in Poland at the end of preschool education and the beginning
      of primary education with respect to selected socioeconomic and educational
      conditions. Data were collected for 742 children from selected Warsaw
      kindergartens in spring 2011 and 2012. Their mean age was 5.84+/-0.31 years. The
      sex categories were equal: 371 boys and 371 girls. Kindergartens chosen for the
      study constituted a representative sample. The diagnostic survey method
      (questionnaire technique) was used to assess the selected environmental
      conditions of development in the participating children. Body height and the sum
      of six skin folds (over the biceps, over the triceps, under the scapula, on the
      abdomen, over the wing of ilium and on the calf) were chosen from the assessed
      anthropometric parameters for the purpose of determining somatic development of
      study participants. The obtained data were analysed using selected descriptive
      statistics methods (including cluster analysis), data standardization
      (normalization by mean values and SD) and the chi-squared test. The results
      showed certain relationships between the selected parameters of somatic
      development and family living conditions. These relationships involved
      differences between individual clusters depending on given living conditions and
      were most prominent for mother's education, for which variable differences
      between clusters were found for both sexes. The somatic build of boys (including
      body height and body adiposity) also differed depending on the number of
      offspring in the family, while the somatic build of girls differed depending on
      father's employment and father's education. Furthermore, the obtained results
      lead to the conclusion that the total number of differences between the analysed
      clusters was relatively low. This indicates that the biological effects of social
      stratification tend to diminish in the environment of an urban agglomeration. 

PMID- 25392126
TI  - Elevation of C-reactive protein during the luteal phase in healthy adolescents.
AB  - INTRODUCTION: Variations in inflammatory markers have been reported in adult
      women during the luteal phase, but whether these findings are observed during
      adolescence is unknown. We postulate that higher ultrasensitive C-reactive
      protein (usCRP) and lower 2-hydroxyestrone (2OHE) levels, an estrogen metabolite
      with cardioprotective actions, are present during the luteal phase in young
      women. AIM: To evaluate usCRP levels during the menstrual cycle and to determine
      its association with 2OHE and 16alpha-hydroxyestrone (16OHE) in adolescents.
      METHODS: Healthy postmenarcheal adolescents (N = 37) were studied during one
      menstrual cycle in follicular phase (FP) and luteal phase-like period (LP-L).
      RESULTS: Elevations in usCRP levels in the LP-L were observed in the entire group
      and in anovulatory cycles (1.9 +/- 1.1 mg/L in FP to 2.5 +/- 1.8 mg/L in LP-L; p
      < 0.0001). Increases in estrone, estradiol, free and bioavailable estradiol,
      testosterone, usCRP and 2OHE levels were observed in LP-L compared with FP (p <
      0.01), with a borderline elevation in IFG-I levels (p = 0.06). CONCLUSIONS: We
      report an elevation of usCRP and 2OHE levels during the luteal phase in healthy
      adolescents. Elevations of this inflammatory marker in anovulatory adolescents
      without an increase in 2OHE may play a role in metabolic risks associated with
      chronic anovulation.

PMID- 25392127
TI  - [Multiple pressure-sensitive, ulcerating nodes on both lower legs of a 84-year
      old woman].

PMID- 25392128
TI  - [Atypical fibroxanthoma of the scalp: overview and recent developments].
AB  - Atypical fibroxanthoma (AFX) is a rare, low-malignant, mesenchymal tumor of the
      dermis and is assigned to the group of fibrohistiocytic tumors. The tumor occurs
      especially in photodamaged skin on the scalp of elderly men. A clinical diagnosis
      is not possible due to a multitude of possible differential diagnoses
      (leiomyosarcoma, squamous cell carcinoma, spindle cell malignant melanoma,
      dermatofibrosarcoma protuberans). Immunohistochemical and histological
      examinations should be performed to confirm the diagnosis. The tumor shows a very
      good prognosis after complete excision. Micrographically controlled surgery is
      considered as the treatment of choice.

PMID- 25392129
TI  - [Focus on the scalp].

PMID- 25392130
TI  - Abeta anti-idiotypic antibodies are present in intravenous immunoglobulin and are
      produced in mice following its administration.
AB  - The effects of intravenous immunoglobulin (IVIG) products were recently examined
      in patients with Alzheimer's disease (AD). Although encouraging results were
      obtained in pilot studies, later trials produced negative results. The rationale
      for these studies was that IVIG contains antibodies to amyloid-beta (Abeta).
      However, if Abeta anti-idiotypic antibodies (antibodies which bind to anti-Abeta
      antibodies) are present in IVIG or induced by its administration, these
      antibodies could potentially reduce its neuroprotective effects in AD. The
      objective of this study was to determine if IVIG contained such antibodies.
      Enzyme-linked immunosorbent assays (ELISAs) measured specific binding of IVIG
      Gamunex to purified human anti-Abeta IgG. The mean concentration of its Abeta
      anti-idiotypic antibodies in four experiments was 1.85 MUg/mL (18.5 MUg/g IgG;
      range = 1.82-1.89 MUg/mL [18.2-18.9 MUg/g IgG]), and their mean percentage of
      specific binding was 72.2% (range = 68.3-75.3%). We then performed ELISAs to
      determine if antibodies to purified human anti-Abeta were produced in C57BL/6
      mice injected with the IVIG product Gammagard in an earlier study. After
      subtracting the expected immune response to normal human immunoglobulins, the
      median concentrations of these antibodies were 15.6 ng/mL (range = 1.2-108.2
      ng/mL) in pre-treatment sera and 2419.4 ng/mL (range = 327.4-8478.4 ng/mL) in
      post-treatment sera. These results indicate that specific Abeta anti-idiotypic
      antibodies are detectable in IVIG and may be induced in mice by its
      administration. The presence of Abeta anti-idiotypic antibodies in IVIG products
      might decrease neuroprotective effects of their anti-Abeta antibodies in AD.

PMID- 25392131
TI  - Accessibility and potency of uterotonic drugs purchased by simulated clients in
      four districts in India.
AB  - BACKGROUND: Surveillance of drug quality for antibiotics, antiretrovirals,
      antimalarials and vaccines is better established than surveillance for maternal
      health drugs in low-income countries, particularly uterotonic drugs for the
      prevention and treatment of postpartum hemorrhage. The objectives of this study
      are to: assess private sector accessibility of four drugs used for uterotonic
      purposes (oxytocin, methylergometrine, misoprostol, valethamate bromide); and to
      assess potency of oxytocin and methylergometrine ampoules purchased by simulated
      clients. METHODS: The study was conducted in Hassan and Bagalkot districts in
      Karnataka state and Agra and Gorakhpur districts in Uttar Pradesh state. A sample
      of 877 private pharmacies was selected (using a stratified, systematic sampling
      with random start), among which 847 were successfully visited. The target sample
      size for assessment of accessibility was 50 pharmacies per drug, per district.
      The target sample size for potency assessment was 100 purchases each of oxytocin
      and methylergometrine across all districts. Successful drug purchases varied by
      state. RESULTS: In Agra and Gorakhpur, 90%-100% of visits for each of the drugs
      resulted in a purchase. In Bagalkot and Hassan, only 29%-52% of visits for each
      drug resulted in a purchase. Regarding potency, the percent of active
      pharmaceutical ingredient was assessed using United States Pharmacopeia monograph
      #33 for both drugs; 193 and 188 ampoules of oxytocin and methylergometrine,
      respectively, were assessed. The percent of oxytocin ampoules outside
      manufacturer specification ranged from 33%-40% in Karnataka and from 22%-50% in
      Uttar Pradesh. In Bagalkot and Hassan, 96% and 100% of the methylergometrine
      ampoules were outside manufacturer specification, respectively. In Agra and
      Gorakhpur, 54% and 44% were outside manufacturer specification, respectively.
      CONCLUSION: Private sector accessibility of uterotonic drugs in study districts
      in Karnataka warrants attention. Most importantly, interventions to assure
      quality oxytocin and particularly methylergometrine are needed in study districts
      in both states.

PMID- 25392132
TI  - Impact of population ageing on the costs of hospitalisations for cardiovascular
      disease: a population-based data linkage study.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the most costly disease in Australia.
      Measuring the impact of ageing on its costs is needed for planning future
      healthcare budget. The aim of this study was to measure the impact of changes in
      population age structure in Western Australia (WA) on the costs of
      hospitalisation for CVD. METHODS: All hospitalisation records for CVD occurring
      in WA in 1993/94 and 2003/04 inclusive were extracted from the WA Hospital
      Morbidity Data System (HMDS) via the WA Data Linkage System. Inflation adjusted
      hospitalisation costs using 2012 as the base year was assigned to all episodes of
      care using Australian Refined Diagnosis Related Group (AR-DRG) costing
      information. The component decomposition method was used to measure the
      contribution of ageing and other factors to the increase of hospitalisation costs
      for CVD. RESULTS: Between 1993/94 and 2003/04, population ageing contributed 23%
      and 30% respectively of the increase in CVD hospitalisation costs for men and
      women. The impact of ageing on hospitalisation costs was far greater for chronic
      conditions than acute coronary syndrome (ACS) and stroke. CONCLUSIONS: Given the
      impact of ageing on hospitalisation costs, and the disparity between chronic and
      acute conditions, disease-specific factors should be considered in planning for
      future healthcare expenditure.

PMID- 25392133
TI  - Qualitative research synthesis for health policy analysis: what does it entail
      and what does it offer?

PMID- 25392134
TI  - Safety, effectiveness, and cost effectiveness of decision aids still unclear.

PMID- 25392135
TI  - Editorial (thematic issue: the (same old) problem of uncontrolled hypertension).

PMID- 25392136
TI  - Sleep apnea: an underestimated cause of resistant hypertension.
AB  - Hypertension is a well established cardiovascular risk factor and its deleterious
      effects had already been largely studied. Although the benefits of adequate blood
      pressure (BP) control have already been demonstrated, the prevalence of persons
      who fail to achieve such control is alarming. A number of causes for uncontrolled
      hypertension can be listed. According to recent guidelines, obstructive sleep
      apnea (OSA) is an important, although neglected cause of hypertension that is
      resistant to optimal medical therapy. Specific treatment for OSA with continuous
      positive airway pressure (CPAP) can be a helpful adjunct to conventional
      pharmacological therapy to attain controlled BP levels. 

PMID- 25392137
TI  - Depression and its relation with uncontrolled hypertension and increased
      cardiovascular risk.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality worldwide and
      hypertension is one of the main cardiovascular risk factors. A large body of
      evidence have demonstrated the increased risk for CVD and mortality associated
      with uncontrolled hypertension and also the benefits of an adequate blood
      pressure (BP) control. In some cases, lack of adherence to treatment found during
      the evaluation of a subject with poor BP control may be part of a more complex
      scenario, as depression. It is known that individuals with depression have a
      higher risk of CVD-related morbidity and mortality, and early diagnosis and
      treatment have beneficial effects. 

PMID- 25392138
TI  - Revisiting the J-curve phenomenon. An old new concept?
AB  - Cohort studies have demonstrated the association between blood pressure and
      increased cardiovascular events. There are different therapeutic strategies to
      achieve goals of systolic and diastolic blood pressure. For a long time,
      therapeutic targets were not well defined and the concept of "smaller is better"
      was used diffusely. However, clinical trials have shown the presence of a "J
      curve" in different clinical situations: below a certain level of blood pressure,
      more aggressive reductions may not represent benefit and increase the incidence
      of adverse events in elderly patients, patients with coronary artery disease,
      patients with diabetes or chronic renal failure. 

PMID- 25392139
TI  - Assessing systemic arterial hypertension through echocardiography: a review for
      the clinician.
AB  - Hypertension is a major cardiovascular (CV) risk factor and elevated blood
      pressure poses a significant burden for the whole CV hemodynamics. Along the last
      decades different techniques and resources have been developed, including
      ultrasound's M-mode and B-mode, spectral Doppler, tissue Doppler and color
      Doppler. Techniques from newer resources as speckle tracking, twist and
      tridimensional ultrasound are continuously being inserted in the echocardiography
      labs routine around the world. Many of the older and newer techniques
      interpretation have a subject component from the echocardiographer. The clinician
      must have minimum technical echocardiography knowledge and assess if the
      echocardiogram data match clinical and other exams data. Systemic arterial
      hypertension leads to morphologic and hemodynamic changes in the heart. These
      changes are signals of progressive damage along the years. Echocardiography is a
      powerful tool to assess these diagnostic and prognostic information. 

PMID- 25392140
TI  - Indications, implications and applications of renal denervation. Have we
      discovered something new?
AB  - Hyperactivity of sympathetic nervous system is one of the main mechanisms to play
      a role in the pathophysiology of hypertension. Its high prevalence and the low
      rates of adequate blood pressure control with pharmacological treatment brought
      interest to novel therapeutical strategies. Percutaneous renal sympathetic
      denervation emerged as an effective and safe alternative to reduce blood pressure
      in patients with resistant hypertension. Other potential indications to this
      procedure are heart failure, cases of insulin resistance, obesity, obstructive
      sleep apnea and cardiac arrhythmias. 

PMID- 25392141
TI  - Isolated perioperative hypertension: clinical implications & contemporary
      treatment strategies.
AB  - Perioperative hypertension has been shown to be a risk factor for the development
      of perioperative morbidity and mortality. The time spent outside acceptable blood
      pressure ranges, in a state of hypertension or hypotension, is correlated with
      the incidence of stroke, acute coronary syndrome, renal dysfunction, and death.
      The ideal perioperative treatment of hypertension would include an easily
      titratable agent, with fast onset and offset and minimal side effects. Several
      medication classes are routinely used in the operating room, including, but not
      limited to, beta-blockers, calcium channel blockers, nitrates, and angiotensin
      converting enzyme (ACE) inhibitors.Proper treatment of chronic hypertension and
      continuation of chronic anti-hypertensive medications in the perioperative period
      has been demonstrated to improve patient outcomes. This review article will
      outline the importance of perioperative blood pressure management, the treatment
      pitfalls, and the novel medications being used in the perioperative setting. 

PMID- 25392142
TI  - Modulation of renin-angiotensin system and arterial stiffness: evidence from
      clinical trials.
AB  - Arterial stiffness has been recognized as an independent risk factor for
      cardiovascular morbidity and mortality in hypertension. The activity of the renin
      angiotensin system(RAS) is well-known to be involved in the control of blood
      pressure, and pathogenesis and evolution of several cardiovascular diseases.
      Although data relating the RAS activity to arterial stiffness are incomplete,
      there is growing evidence which shows that drugs which interfere with angiotensin
      II reduce arterial stiffness. This brief review is to summarize the various
      effects of commonly used antihypertensive agents on arterial stiffness and to
      present clinical trials regarding RAS modulation in stiffness reduction. 

PMID- 25392143
TI  - Impact of patient knowledge of hypertension complications on adherence to
      antihypertensive therapy.
AB  - BACKGROUND: Poor adherence is thought to be one of the major common causes of
      uncontrolled high blood pressure over the world leading to useless drug dose or
      class changes which may lead to increased adverse effects and medical costs. The
      current study aimed to investigate the relationship between knowledge about
      complications related to hypertension and adherence to antihypertensive
      treatment. MATERIALS AND METHODS: A cross-sectional study was carried out between
      May and November 2013 on a representative sample of 453 hypertensive patients at
      public primary care outpatients in the department of Tlemcen in Algeria. The
      adherence was assessed with the adherence evaluation scale of Girerd which
      contains six items with closed dichotomous responses (yes/no). The degree of
      adherence was calculated according to the score resulting from the sum of all
      "yes" answers. A cut-off value of 80% was used to categorize patients as
      "adherent" or "non-adherent". To do so, a structured questionnaire has been
      performed including patients' knowledge about hypertension complications and the
      other factors which may affect adherence therapy. RESULTS: Among the 453 patients
      included in the study, only 35.5% were adherents. Univariate analysis has shown a
      positive relationship between knowledge about hypertension complications and
      adherence. However, comorbidities, and number of antihypertensive drugs
      prescribed, were associated with poor adherence. In a multivariate analysis, a
      significant difference was shown between adherents and non-adherents according to
      the factors mentioned above and the insurance status. CONCLUSION: This study has
      shown a positive relationship between patients' knowledge about the hypertensive
      complications and adherence. In contrast, increased number of antihypertensive
      drugs taken May affect negatively the adherence to therapy.

PMID- 25392144
TI  - Brachial-ankle pulse wave velocity in the measurement of arterial stiffness:
      recent evidence and clinical applications.
AB  - Arterial stiffness is a vascular measure that has been reported to predict
      cardiovascular events. It is important to measure arterial stiffness in order to
      determine current vascular status and treatment strategy. Brachial-ankle pulse
      wave velocity (baPWV) is a unique measure of systemic arterial stiffness that is
      measured by brachial and tibial arterial wave analyses. Measurement of baPWV is
      easy and is reproducible. For more than a decade, this measure has been used
      broadly in East Asian countries. Meta-analysis of cohort studies conducted in the
      general population with hypertension, diabetes, or end-stage renal disease, and
      other high-risk individuals have shown that a 1 m/s increase in baPWV is
      associated with 12% increase in the risk of cardiovascular events. Thus, the
      Japanese Circulation Society has proposed that a baPWV of 1800 cm/s is a
      threshold for high-risk category. For baPWV to be clinically applicable, we must
      confirm that circulation of the lower limbs are normal by examining brachial
      ankle blood pressure index. In cases of peripheral arterial disease, the
      reliability of baPWV measurement is attenuated. To further confirm the clinical
      usefulness of this measure, we need to examine the hypothesis that baPWV-guided
      therapy could improve prognosis in high-risk patients. 

PMID- 25392145
TI  - Long term safety and efficacy of internal carotid artery adventitial stripping in
      carotid sinus syndrome.
AB  - BACKGROUND: To investigate the long term efficacy of carotid denervation by
      adventitial stripping of the internal carotid artery (ICA) for carotid sinus
      syndrome (CSS). Secondly, the long term safety of this technique is investigated
      with emphasis on the effects on blood pressure (BP), heart rate (HR) and carotid
      artery diameter. METHODS: Characteristics of patients that were operated for CSS
      in a single institute between 1980-2007 were studied by a retrospective chart
      review. Alive and fit patients additionally received a standardized interview
      investigating symptoms of residual CSS or baroreflex failure. They underwent a
      test panel consisting of office BP measurement, carotid sinus massage (CSM),
      table tilt testing, 24-hour ECG and ambulatory BP measurement (ABPM) and carotid
      duplex. Unoperated, age- and sex- matched individuals without CSS served as
      controls. RESULTS: After a total follow up of 91+/-34 months, 22 of 26 patients
      (85%) were asymptomatic and 20 of them (77%) without a pacemaker. Of the 7
      surviving and fit patients, six were free of CSS symptoms (follow up 114 +/- 81
      months). Recurrence of CSS after an initial successful carotid denervation was
      not observed. BP level, BP variability and carotid diameters were not different
      compared to controls. CONCLUSION: Carotid denervation by adventitial stripping of
      the ICA for CSS seems effective and safe on the long term. A randomized
      controlled trial comparing the efficacy and safety of carotid denervation, pacing
      and medical treatment is needed for optimal future treatment of patients
      suffering from CSS.

PMID- 25392146
TI  - Misclassification of obesity in CKD: appearances are deceptive.

PMID- 25392148
TI  - Acrylamide induces specific DNA adduct formation and gene mutations in a
      carcinogenic target site, the mouse lung.
AB  - Acrylamide (AA) is a contaminant in heated foods and is carcinogenic in multiple
      organs of rodents. There have been many reports regarding AA-induced DNA
      modification and genotoxicity. However, the data are insufficient to understand
      fully the relationship between the two events. A recent report demonstrated
      carcinogenicity in the mouse lung. The lung is advantageous for investigation of
      AA-induced genotoxicity because DNA adduct levels are relatively high in this
      organ. In the present study, reporter gene mutation assays and quantitative
      analyses of specific DNA adducts were performed in the lungs of mature gpt delta
      mice treated with AA at doses of 100, 200 and 400 p.p.m. in drinking water for 4
      weeks. N7-GA-Gua was detected in all AA-treated mice in a dose-dependent manner.
      gpt mutant frequencies (MFs) were significantly increased in the middle- and high
      dose groups. In the analysis of mutation spectra, significant increases in GC-TA
      transversions and single base deletion mutations were observed in the high-dose
      group. Spi(-) MFs were significantly increased in the high-dose group. Analysis
      of Spi(-) mutants revealed significant increases in the frequencies of single
      base deletion mutation in runs of G/C and A/T. Analyses of immature mice under
      the same experimental conditions showed that there were no differences of
      susceptibility to AA-induced genotoxicity in the two age classes. The overall
      data clearly show the causal relationship between AA-induced DNA adducts and the
      gene mutations at carcinogenic target sites. 

PMID- 25392147
TI  - Association of sarcopenia with eGFR and misclassification of obesity in adults
      with CKD in the United States.
AB  - BACKGROUND AND OBJECTIVES: Muscle wasting is common among patients with ESRD, but
      little is known about differences in muscle mass in persons with CKD before the
      initiation of dialysis. If sarcopenia was common, it might affect the use of body
      mass index for diagnosing obesity in people with CKD. Because obesity may be
      protective in patients with CKD and ESRD, an accurate understanding of how
      sarcopenia affects its measurement is crucial. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Differences in body composition across eGFR categories in adult
      participants of the National Health and Nutrition Examination Survey 1999-2004
      who underwent dual-energy x-ray absorptiometry were examined. Obesity defined by
      dual-energy x-ray absorptiometry versus body mass index and sarcopenia as a
      contributor to misclassification by body mass index were examined. RESULTS:
      Sarcopenia and sarcopenic obesity were more prevalent among persons with lower
      eGFR (P trend <0.01 and P trend <0.001, respectively). After multivariable
      adjustment, the association of sarcopenia with eGFR was U-shaped. Stage 4 CKD was
      independently associated with sarcopenia among participants >=60 years old
      (adjusted odds ratio, 2.58; 95% confidence interval, 1.02 to 6.51 for eGFR=15-29
      compared with 60-89 ml/min per 1.73 m(2); P for interaction by age=0.02).
      Underestimation of obesity by body mass index compared with dual-energy x-ray
      absorptiometry increased with lower eGFR (P trend <0.001), was greatest among
      participants with eGFR=15-29 ml/min per 1.73 m(2) (71% obese by dual-energy x-ray
      absorptiometry versus 41% obese by body mass index), and was highly likely among
      obese participants with sarcopenia (97.7% misclassified as not obese by body mass
      index). CONCLUSIONS: Sarcopenia and sarcopenic obesity are highly prevalent among
      persons with CKD and contribute to poor classification of obesity by body mass
      index. Measurements of body composition beyond body mass index should be used
      whenever possible in the CKD population given this clear limitation.

PMID- 25392149
TI  - Chemopreventive mechanism of polypeptides from Chlamy Farreri (PCF) against UVB
      induced malignant transformation of HaCaT cells.
AB  - To investigate polypeptide from Chlamy Farreri (PCF)'s protective effect against
      skin cancer, we used a cellular model of ultraviolet B (UVB)-induced malignant
      transformation. The human keratinocyte cell line HaCaT was repeatly exposed to
      UVB (10 mJ/cm(2), 20 times) and malignant transformation was confirmed by Gimesa
      staining, cell cycle analysis and various assays [anchorage independent growth,
      matrix metalloproteinase-9 (MMP9) activity, plating efficiency]. The malignant
      transformation was found to be effectively prevented by PCF pretreatment (2.84mM
      for 2h prior to each UVB exposure). We investigated the mechanism of PCF-mediated
      action by determining its effect on DNA methylation status of the tumour
      suppressor genes [P16 and ras association domain family 1 A (RASSF1A)] in the UVB
      transformed cells. Both genes were found to be hypermethylated by chronic UVB
      exposure. The expression levels of P16, RASSF1A, DNA methyltransferases (DNMTs)
      and DNA damage inducible protein a (GADD45a) were measured by reverse
      transcriptase-polymerase chain reaction and western blotting. While chronic UVB
      exposure was found to suppress the expression of P16 and RASSF1A, it enhanced the
      expression of DNMT3b. In the early phase of UVB-induced malignant transformation,
      the GADD45a expression was increased, however, it declined with a continued
      irradiation of the cells. The UVB-induced DNA hypermethylation of P16 and RASSF1A
      and subsequent gene silencing was reversed by PCF treatment. The inhibition of
      DNMTs expression suggested that PCF blocked DNA methylation and thereby the
      silencing of tumour suppressor genes. Furthermore, the PCF-mediated substantial
      increase in GADD45a expression indicated that PCF promoted demethylation of
      tumour suppressor genes via GADD45a induction. 

PMID- 25392150
TI  - Cognitive Task Analysis: Bringing Olympic Athlete Style Training to Surgical
      Education.
AB  - BACKGROUND: Surgical training is changing and evolving as time, pressure, and
      legislative demands continue to mount on trainee surgeons. A paradigm change in
      the focus of training has resulted in experts examining the cognitive steps
      needed to perform complex and often highly pressurized surgical procedures.
      OBJECTIVE: To provide an overview of the collective evidence on cognitive task
      analysis (CTA) as a surgical training method, and determine if CTA improves a
      surgeon's performance as measured by technical and nontechnical skills
      assessment, including precision, accuracy, and operative errors. METHODS: A
      systematic literature review was performed. PubMed, Cochrane, and reference lists
      were analyzed for appropriate inclusion. RESULTS: A total of 595 surgical
      participants were identified through the literature review and a total of 13
      articles were included. Of these articles, 6 studies focused on general surgery,
      2 focused on practical procedures relevant to surgery (central venous
      catheterization placement), 2 studies focused on head and neck surgical
      procedures (cricothyroidotomy and percutaneous tracheostomy placement), 2 studies
      highlighted vascular procedures (endovascular aortic aneurysm repair and carotid
      artery stenting), and 1 detailed endovascular repair (abdominal aorta and
      thoracic aorta). Overall, 92.3% of studies showed that CTA improves surgical
      outcome parameters, including time, precision, accuracy, and error reduction in
      both simulated and real-world environments. CONCLUSION: CTA has been shown to be
      a more effective training tool when compared with traditional methods of surgical
      training. There is a need for the introduction of CTA into surgical curriculums
      as this can improve surgical skill and ultimately create better patient outcomes.

PMID- 25392151
TI  - Laparoscopic Inguinal Hernia Repair With a Novel Hernia Mesh Incorporating a
      Nitinol Alloy Frame Compared With a Standard Lightweight Polypropylene Mesh.
AB  - BACKGROUND: Numerous mesh materials are available for laparoscopic inguinal
      hernia repair. The role of fixation of mesh in laparoscopic inguinal hernia
      repair remains controversial. Mesh materials have been engineered to anatomically
      conform to the pelvis to potentially reduce or eliminate the need for fixation.
      This study evaluates the outcomes of laparoscopic inguinal hernia utilizing a
      device consisting of a lightweight polypropylene mesh with a nitinol frame
      (Rebound HRD) compared with repair with lightweight polypropylene mesh with
      permanent tack fixation. METHODS: A prospective randomized trial evaluating the
      outcomes of laparoscopic inguinal hernia repair with a lightweight polypropylene
      mesh with a nitinol frame (N-LWM) compared with standard lightweight
      polypropylene mesh (LWM) was conducted. Randomization was performed at an N-LWM
      to LWM ratio of 2:1. Repairs were standardized to a laparoscopic extraperitoneal
      approach without fixation for N-LWM and titanium tack fixation for LWM repairs.
      Follow-up assessments were performed at 7 days, 6 months, and 1 year. Outcome
      measures include visual analog pain scale (VAS), Short Form 36 (SF-36), Carolinas
      Comfort Scale (CCS), operative details, complications, and recurrences. RESULTS:
      There were 47 patients that underwent laparoscopic inguinal hernia repair and
      adhered to study protocol (31 N-LWM, 16 LWM). The groups did not differ
      significantly in age, body mass index, ethnicity, or employment. The N-LWM group
      had bilateral mesh placed in 51.6% and LWM 43.8% (P = .76). Operative duration
      was similar, 59.6 +/- 23.1 minutes for LWM and 62.4 +/- 26.7 minutes for N-LWM (P
      = .705) as was mesh handling time was 5.4 +/- 3.1 minutes LWM versus 7.3 +/- 3.9
      minutes N-LWM (P = .053). VAS, CCS, and SF-36 survey results were similar between
      groups. There was one recurrence (0.03%) in the N-LWM group. CONCLUSIONS: Nitinol
      framed lightweight polypropylene mesh may be safely used during laparoscopic
      inguinal hernia repair with outcomes comparable to LWM at 1 year. N-LWM does not
      impact operating room time, mesh handling time, pain, recurrences, or
      complications.

PMID- 25392152
TI  - Modified Approach for Robotic Retroauricular Thyroidectomy: Preclinical
      Simulation and a Surgical Case.
AB  - BACKGROUND: Recently, a single remote access retroauricular robotic technique has
      been described for thyroid lobectomy. We aimed to explore the feasibility and
      safety of modifying this novel approach using preclinical cadaver model followed
      by performing the same operation in a real patient. METHODS: The modified
      retroauricular approach was performed by creating a working space between the 2
      heads of the sternocleidomastoid muscle, instead of that anterior to muscle. This
      was performed to create a wider working space. Two operations were initially
      performed in human cadavers. Subsequently, robotic-assisted thyroid lobectomy was
      performed using this novel modified retroauricular approach. RESULTS: Robotic
      assisted hemithyroidectomy was performed successfully in 2 cadavers and
      subsequently in one patient using modified approach. The patient was discharged
      on the same day of surgery and had no complications. CONCLUSIONS: The modified
      retroauricular approach with creation of a working space between the 2 heads of
      sternocleidomastoid muscle is safe and feasible, and offers a wider working space
      for robotic thyroid surgery.

PMID- 25392153
TI  - Effects of superparamagnetic iron oxide nanoparticles on photosynthesis and
      growth of the aquatic plant Lemna gibba.
AB  - Toxicity of superparamagnetic iron oxide nanoparticles (SPION) was investigated
      in Lemna gibba plants exposed for 7 days to Fe3O4 (SPION-1), Co0.2Zn0.8Fe2O4
      (SPION-2), or Co0.5Zn0.5Fe2O4 (SPION-3) at 0, 12.5, 25, 50, 100, 200 or 400 ug
      mL(-1). At < 400 ug mL(-1) of SPION exposure, toxicity was indicated by decrease
      of chlorophyll content, deterioration of photosystem II (PSII) functions, strong
      production of reactive oxygen species (ROS), and inhibition of growth rate based
      on fresh weight (52-59 %) or frond number (32-49 %). The performance index of
      PSII activity was the most sensitive biomarker of PSII functions and decreased by
      83, 86, and 79 % for SPION-1, SPION-2, and SPION-3, respectively. According to
      the change of these biomarkers, the exposure of SPION suspensions to L. gibba
      caused several alterations to the entire plant cellular system, which may come
      from both the uptake of nanoparticles and metal ions in the soluble fraction. Our
      results, based on the change of several biomarkers, showed that these SPION have
      a complex toxic mode of action on the entire plant system and therefore affects
      its viability. Therefore, the plant model L. gibba was shown to be a sensitive
      bioindicator of SPION cellular toxicity and thus can be used in the development
      of a laboratory bioassay toxicity testing. 

PMID- 25392154
TI  - Exploring the impacts of two separate mixtures of pesticide and surfactants on
      estrogenic activity in male fathead minnows and rainbow trout.
AB  - In this study, male fathead minnows (FHM) (Pimephales promelas) and juvenile
      rainbow trout (RT; Oncorhynchus mykiss) were exposed to two different surfactant
      mixtures of analytical-grade nonlyphenol, 4-tert octyphenol, octylphenol
      ethoxylates, nonylphenol ethoxylates, and the herbicide 2,4-dichlorophenoxyacetic
      acid (2,4-D). After a 7-days exposure to environmentally relevant concentrations
      of these compounds, there was no difference in the relative mRNA expression of
      vitellogenin (VTG) in male juvenile RT exposed to individual compounds or the 2,4
      D-surfactant mixture compared with the control. In male FHM, there was a
      significant increase in VTG mRNA expression in the high individual treatments of
      2,4-D and the surfactants but not the 2,4-D-surfactant mixtures compared with the
      control. These results were compared with another study exposing male FHM to
      individual and a mixture of alkylphenols and alkylphenol ethoxylates in two
      different combinations with the herbicide diuron and the insecticide bifenthrin.
      There were no differences in the relative expression of VTG mRNA amongst
      individual exposures and the control. Interestingly, when the ethoxylate mixture
      was combined with diuron, there was a significant decrease in the relative mRNA
      expression of VTG compared with the control. However, when the ethoxylate mixture
      was combined with both diuron and bifenthrin, there was a significant increase in
      the relative mRNA expression of VTG in male compared with all other groups in the
      multichemical mixture. The results of this study highlight differences between
      species and measurements of VTG in assessing the risk of mixtures to aquatic
      organisms.

PMID- 25392155
TI  - Postmortem imaging in congenital heart disease: preliminary experience.
AB  - BACKGROUND: Despite the importance of the autopsy for quality improvement,
      autopsy rates have declined dramatically in recent decades due to poor acceptance
      by families and physicians and high costs to institutions. PURPOSE: To compare
      postmortem imaging (PMI) with autopsy in patients with congenital heart defects
      to see if PMI could substitute in some or all cases and to compare costs of the
      two methods. MATERIAL AND METHODS: Ten patients with congenital heart disease
      dying in hospital during the study period in whom an autopsy was planned
      underwent PMI using postmortem magnetic resonance imaging (PMMRI) (6 patients)
      and postmortem computed tomographic angiography (PMCTA) (10 patients) with
      permission of the family. Four patients were excluded from PMMR because of metal
      ECMO cannulas. PMI was interpreted before autopsy using an organ system checklist
      and results compared to autopsy. The costs of each method were tracked. RESULTS:
      When both PMMR and PMCTA were performed the PMI findings corresponded closely
      with autopsy. PMI correctly diagnosed the principal heart defects in all six
      cases and correctly imaged central vessels, heart valves and chambers, brain,
      abdominal organs, and bone. Weak points were visualization of the coronary
      arteries and distinguishing postmortem pulmonary atelectasis from lung pathology.
      The cause of death by PMI matched autopsy findings in 5/6 cases in which both
      PMMR and PMCTA were performed and was incomplete in the other five cases. The
      cost of PMI was about 15% lower than the cost of autopsy. CONCLUSION: PMI
      provided most gross anatomic cardiac diagnoses available by autopsy in our series
      of patients with congenital heart defects and the cost appears to be lower.

PMID- 25392156
TI  - The role of chemotherapy for metastatic, relapsed and refractory osteosarcoma.
AB  - Despite a large number of publications on outcomes of second-line chemotherapy
      for osteosarcoma, there is little consensus on efficacy of the therapy.
      OBJECTIVE: Our objective was to systematically categorize published evidence for
      chemotherapy for metastatic, relapsed and refractory osteosarcoma in order to
      provide an updated and comprehensive analysis of the clinical outcomes. METHODS:
      We performed a search of PubMed and EMBASE to identify published articles
      reporting on validated clinical outcomes measures (the rate of complete response
      [CR] and partial response [PR], the rate of stable disease [SD] and progressive
      disease [PD] and the 5-year overall survival) after chemotherapy in patients with
      metastatic, relapsed and refractory osteosarcoma. A total of 20 articles were
      identified and stratified by different regimens. Finally, six regimens that have
      at least two drugs were reviewed. Weighted averages of each outcome were
      computed. RESULTS: The weighted average overall response rate (CR + PR) for the
      combination of ifosfamide, etoposide and high-dose methotrexate therapy was 62 %,
      and the tumor control rate (CR + PR + SD) was 92.3 %; the highest of all six
      regimens. The weighted average overall response rate and tumor control rate of
      ifosfamide-etoposide therapy (41.7 and 77.9 %, respectively) were the highest of
      the two-drug regimens. Weighted average overall response rate and tumor control
      rate for the remaining regimens were 20.5 and 56.8 %, respectively, for
      cyclophosphamide-etoposide; 30.0 and 73.5 % for ifosfamide, carboplatin, and
      etoposide; 12.0 and 40.0 % for cyclophosphamide-topotecan; and 14.5 and 36.4 %
      for gemcitabine-docetaxel. CONCLUSION: A chemotherapy regimen comprising both a
      cell cycle-specific drug and a cell cycle-nonspecific drug could increase
      response rates. The combination of ifosfamide and etoposide therapy is our first
      choice in two-drug regimens. Regarding three-drug regimens, adding a cell cycle
      specific drug to ifosfamide-etoposide therapy may result in a better response
      rate than adding a cell cycle-nonspecific drug, or any other two-drug regimens in
      current studies. Hence, we recommend the use of second-line chemotherapy based on
      the combination ifosfamide-etoposide regimen in patients with metastatic,
      relapsed and refractory osteosarcoma.

PMID- 25392157
TI  - Long-term outcome of patients with clinical stage I high-risk nonseminomatous
      germ-cell tumors 15 years after one adjuvant cycle of bleomycin, etoposide, and
      cisplatin chemotherapy.
AB  - BACKGROUND: To report the long-term results of adjuvant treatment with one cycle
      of modified bleomycin, etoposide, and cisplatin (BEP) in patients with clinical
      stage I (CS I) nonseminomatous germ-cell tumors (NSGCT) at high risk of relapse.
      PATIENTS AND METHODS: In a single-arm, phase II clinical trial, 40 patients with
      CS I NSGCT with vascular invasion and/or >50% embryonal cell carcinoma in the
      orchiectomy specimen received one cycle of adjuvant BEP (20 mg/m(2) bleomycin as
      a continuous infusion over 24 h, 120 mg/m(2) etoposide and 40 mg/m(2) cisplatin
      each on days 1-3). Primary end point was the relapse rate. RESULTS: Median follow
      up was 186 months. One patient (2.5%) had a pulmonary relapse 13 months after one
      BEP and died after three additional cycles of BEP chemotherapy. Three patients
      (7.5%) presented with a contralateral metachronous testicular tumor, and three
      (7.5%) developed a secondary malignancy. Three patients (7.5%) reported
      intermittent tinnitus and one had grade 2 peripheral polyneuropathy (2.5%).
      CONCLUSIONS: Adjuvant chemotherapy with one cycle of modified-BEP is a feasible
      and safe treatment of patients with CS I NSGCT at high risk of relapse. In these
      patients, it appears to be an alternative to two cycles of BEP and to have a
      lower relapse rate than retroperitoneal lymph node dissection. If confirmed by
      other centers, 1 cycle of adjuvant BEP chemotherapy should become a first-line
      treatment option for this group of patients.

PMID- 25392158
TI  - Upfront allogeneic stem-cell transplantation for patients with nonlocalized
      untreated peripheral T-cell lymphoma: an intention-to-treat analysis from a
      single center.
AB  - BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous
      diseases with dismal outcome when treated with chemotherapy alone. Because
      allogeneic stem-cell transplantation (allo-SCT) can cure relapse/refractory
      patients, we hypothesized that upfront allo-SCT may provide a better outcome.
      Therefore, all patients that presented with advanced PTCL in our institution at
      diagnosis were scheduled to undergo upfront allo-SCT after induction
      chemotherapy. PATIENTS AND METHODS: The aim of the present work was to assess the
      feasibility and toxicity of upfront allo-SCT. From 2004 to 2012, 49 newly
      diagnosed PTCL patients were scheduled to receive upfront allo-SCT. A human
      leukocyte antigen-matched donor was found for 42 patients: related to the patient
      in 15 cases, unrelated in 20 cases, and suitable cord blood units were used in 7
      cases. RESULTS: After induction chemotherapy, 17 patients reached complete
      remission and 29 (60%) proceeded to upfront allo-SCT. For all patients, the 1 and
      2-year overall survival (OS) rates were 59% [95% confidence interval (CI) 47-75]
      and 55% (95% CI 43-71), respectively. The most frequent reason we did not proceed
      to allo-SCT was disease progression or insufficient response after induction. For
      transplanted patients, the 1- and 2-year OS were 76% (95% CI 62-93) and 72.5%
      (95% CI 58-91), respectively. Toxicity-related mortality (TRM) 1 year after allo
      SCT was only 8.2% (95% CI 0-18.5). The 2-year progression-free survival (PFS)
      rate of patients who did not proceed to allo-SCT (n = 20) was below 30%. The
      disease status at the time of transplantation was a strong predictive marker for
      both PFS and OS in transplant patients. CONCLUSIONS: Upfront allo-SCT in PTCLs is
      feasible with low TRM, and it provides long-term disease control. However, one
      third of patients remain chemo-refractory and, thus, new therapeutic approaches
      are warranted. The role of upfront allo-SCT compared with other therapeutic
      approaches in PTCLs requires investigation in randomized studies.

PMID- 25392159
TI  - Marked transient hypercholesterolemia caused by low-dose mitotane as adjuvant
      chemotherapy for adrenocortical carcinoma.
AB  - We herein report a case of marked transient hypercholesterolemia in a man
      receiving low-dose mitotane as adjuvant chemotherapy for adrenocortical
      carcinoma.A 58-year-old man without any clinical symptoms or history of
      hypercholesterolemia was admitted to our hospital to treat an adrenocortical
      carcinoma detected on general screening using computed tomography. He reported no
      chest symptom and did not exhibit any established risk factors for coronary
      artery disease, such as diabetes, obesity, hypertension or relevant family
      history, with the exception of current smoking, on admission. A stress
      electrocardiogram showed negative findings. The left adrenal tumor as well as
      left kidney, spleen and distal portion of the pancreas were subsequently resected
      using radical surgery. The histopathological findings confirmed the preoperative
      diagnosis of adrenocortical carcinoma. After the operation, treatment with low
      dose mitotane (1g/day) was introduced as adjuvant chemotherapy. Interestingly,
      the patient developed marked hyper-LDL cholesterolemia at a level equivalent to
      that of familial hypercholesterolemia (LDL cholesterol level ~ 300 mg/dL)
      following the introduction of mitotane, without evidence of primary or secondary
      hypercholesterolemia due to other causes. A coronary angiogram performed to
      assess the new-onset angina revealed three-vessel disease, which was later
      revascularized via percutaneous coronary intervention eight months after the
      start of mitotane therapy. The cholesterol level normalized with the suspension
      of mitotane. This case suggests that mitotane can cause severe
      hypercholesterolemia, potentially resulting in coronary atherosclerosis. 

PMID- 25392160
TI  - What does a neuron learn from multisensory experience?
AB  - The brain's ability to integrate information from different senses is acquired
      only after extensive sensory experience. However, whether early life experience
      instantiates a general integrative capacity in multisensory neurons or one
      limited to the particular cross-modal stimulus combinations to which one has been
      exposed is not known. By selectively restricting either visual-nonvisual or
      auditory-nonauditory experience during the first few months of life, the present
      study found that trisensory neurons in cat superior colliculus (as well as their
      bisensory counterparts) became adapted to the cross-modal stimulus combinations
      specific to each rearing environment. Thus, even at maturity, trisensory neurons
      did not integrate all cross-modal stimulus combinations to which they were
      capable of responding, but only those that had been linked via experience to
      constitute a coherent spatiotemporal event. This selective maturational process
      determines which environmental events will become the most effective targets for
      superior colliculus-mediated shifts of attention and orientation. 

PMID- 25392161
TI  - Transient activity in monkey area MT represents speed changes and is correlated
      with human behavioral performance.
AB  - Neurons in the middle temporal area (MT) respond to motion onsets and speed
      changes with a transient-sustained firing pattern. The latency of the transient
      response has recently been shown to correlate with reaction time in a speed
      change detection task, but it is not known how the sign, the amplitude, and the
      latency of this response depend on the sign and the magnitude of a speed change,
      and whether these transients can be decoded to explain speed change detection
      behavior. To investigate this issue, we measured the neuronal representation of a
      wide range of positive and negative speed changes in area MT of fixating macaques
      and obtained three major findings. First, speed change transients not only
      reflect a neuron's absolute speed tuning but are shaped by an additional gain
      that scales the tuned response according to the magnitude of a relative speed
      change. Second, by means of a threshold model positive and negative population
      transients of a moderate number of MT neurons explain detection of both positive
      and negative speed changes, respectively, at a level comparable to human
      detection rates under identical visual stimulation. Third, like reaction times in
      a psychophysical model of velocity detection, speed change response latencies
      follow a power-law function of the absolute difference of a speed change. Both
      this neuronal representation and its close correlation with behavioral measures
      of speed change detection suggest that neuronal transients in area MT facilitate
      the detection of rapid changes in visual input. 

PMID- 25392162
TI  - Interconnection and synchronization of neuronal populations in the mouse medial
      septum/diagonal band of Broca.
AB  - The medial septum/diagonal band of Broca (MS/DBB) is crucial for hippocampal
      theta rhythm generation (4-12 Hz). However, the mechanisms behind theta
      rhythmogenesis are still under debate. The MS/DBB consists, in its majority, of
      three neuronal populations that use acetylcholine, GABA, or glutamate as
      neurotransmitter. While the firing patterns of septal neurons enable the MS/DBB
      to generate rhythmic output critical for the generation of the hippocampal theta
      rhythm, the ability to synchronize these action potentials is dependent on the
      interconnectivity between the three major MS/DBB neuronal populations, yet little
      is known about intraseptal connections. Here we assessed the connectivity between
      pairs of MS/DBB neurons with paired patch-clamp recordings. We found that
      glutamatergic and GABAergic neurons provide intraseptal connections and produce
      sizable currents in MS/DBB postsynaptic cells. We also analyzed linear and
      nonlinear relationships between the action potentials fired by pairs of neurons
      belonging to various MS/DBB neuronal populations. Our results show that while the
      synchrony index for action potential firing was significantly higher in pairs of
      GABAergic neurons, coherence of action potential firing in the theta range was
      similarly low in all pairs analyzed. Recurrence analysis demonstrated that
      individual action potentials were more recurrent in cholinergic neurons than in
      other cell types. Implementing sparse connectivity in a computer model of the
      MS/DBB network reproduced our experimental data. We conclude that the interplay
      between the intrinsic membrane properties of different MS/DBB neuronal
      populations and the connectivity among these populations underlie the ability of
      the MS/DBB network to critically contribute to hippocampal theta rhythmogenesis. 

PMID- 25392163
TI  - Extracting information in spike time patterns with wavelets and information
      theory.
AB  - We present a new method to assess the information carried by temporal patterns in
      spike trains. The method first performs a wavelet decomposition of the spike
      trains, then uses Shannon information to select a subset of coefficients carrying
      information, and finally assesses timing information in terms of decoding
      performance: the ability to identify the presented stimuli from spike train
      patterns. We show that the method allows: 1) a robust assessment of the
      information carried by spike time patterns even when this is distributed across
      multiple time scales and time points; 2) an effective denoising of the raster
      plots that improves the estimate of stimulus tuning of spike trains; and 3) an
      assessment of the information carried by temporally coordinated spikes across
      neurons. Using simulated data, we demonstrate that the Wavelet-Information (WI)
      method performs better and is more robust to spike time-jitter, background noise,
      and sample size than well-established approaches, such as principal component
      analysis, direct estimates of information from digitized spike trains, or a
      metric-based method. Furthermore, when applied to real spike trains from monkey
      auditory cortex and from rat barrel cortex, the WI method allows extracting
      larger amounts of spike timing information. Importantly, the fact that the WI
      method incorporates multiple time scales makes it robust to the choice of partly
      arbitrary parameters such as temporal resolution, response window length, number
      of response features considered, and the number of available trials. These
      results highlight the potential of the proposed method for accurate and objective
      assessments of how spike timing encodes information. 

PMID- 25392164
TI  - Cutaneous reflex modulation and self-induced reflex attenuation in cerebellar
      patients.
AB  - Modulation of cutaneous reflexes is important in the neural control of walking,
      yet knowledge about underlying neural pathways is still incomplete. Recent
      studies have suggested that the cerebellum is involved. Here we evaluated the
      possible roles of the cerebellum in cutaneous reflex modulation and in
      attenuation of self-induced reflexes. First we checked whether leg muscle
      activity during walking was similar in patients with focal cerebellar lesions and
      in healthy control subjects. We then recorded cutaneous reflex activity in leg
      muscles during walking. Additionally, we compared reflexes after standard
      (computer triggered) stimuli with reflexes after self-induced stimuli for both
      groups. Biceps femoris and gastrocnemius medialis muscle activity was increased
      in the patient group compared with the control subjects, suggesting a
      coactivation strategy to reduce instability of gait. Cutaneous reflex modulation
      was similar between healthy control subjects and cerebellar patients, but the
      latter appeared less able to attenuate reflexes to self-induced stimuli. This
      suggests that the cerebellum is not primarily involved in cutaneous reflex
      modulation but that it could act in attenuation of self-induced reflex responses.
      The latter role in locomotion would be consistent with the common view that the
      cerebellum predicts sensory consequences of movement. 

PMID- 25392165
TI  - Muscarinic presynaptic modulation in GABAergic pallidal synapses of the rat.
AB  - The external globus pallidus (GPe) is central for basal ganglia processing. It
      expresses muscarinic cholinergic receptors and receives cholinergic afferents
      from the pedunculopontine nuclei (PPN) and other regions. The role of these
      receptors and afferents is unknown. Muscarinic M1-type receptors are expressed by
      synapses from striatal projection neurons (SPNs). Because axons from SPNs project
      to the GPe, one hypothesis is that striatopallidal GABAergic terminals may be
      modulated by M1 receptors. Alternatively, some M1 receptors may be postsynaptic
      in some pallidal neurons. Evidence of muscarinic modulation in any of these
      elements would suggest that cholinergic afferents from the PPN, or other sources,
      could modulate the function of the GPe. In this study, we show this evidence
      using striatopallidal slice preparations: after field stimulation in the
      striatum, the cholinergic muscarinic receptor agonist muscarine significantly
      reduced the amplitude of inhibitory postsynaptic currents (IPSCs) from synapses
      that exhibited short-term synaptic facilitation. This inhibition was associated
      with significant increases in paired-pulse facilitation, and quantal content was
      proportional to IPSC amplitude. These actions were blocked by atropine,
      pirenzepine, and mamba toxin-7, suggesting that receptors involved were M1. In
      addition, we found that some pallidal neurons have functional postsynaptic M1
      receptors. Moreover, some evoked IPSCs exhibited short-term depression and a
      different kind of modulation: they were indirectly modulated by muscarine via the
      activation of presynaptic cannabinoid CB1 receptors. Thus pallidal synapses
      presenting distinct forms of short-term plasticity were modulated differently. 

PMID- 25392166
TI  - Stimulus-timing-dependent modifications of rate-level functions in animals with
      and without tinnitus.
AB  - Tinnitus has been associated with enhanced central gain manifested by increased
      spontaneous activity and sound-evoked firing rates of principal neurons at
      various stations of the auditory pathway. Yet, the mechanisms leading to these
      modifications are not well understood. In a recent in vivo study, we demonstrated
      that stimulus-timing-dependent bimodal plasticity mediates modifications of
      spontaneous and tone-evoked responses of fusiform cells in the dorsal cochlear
      nucleus (DCN) of the guinea pig. Fusiform cells from sham animals showed
      primarily Hebbian learning rules while noise-exposed animals showed primarily
      anti-Hebbian rules, with broadened profiles for the animals with behaviorally
      verified tinnitus (Koehler SD, Shore SE. J Neurosci 33: 19647-19656, 2013a). In
      the present study we show that well-timed bimodal stimulation induces alterations
      in the rate-level functions (RLFs) of fusiform cells. The RLF gains and maximum
      amplitudes show Hebbian modifications in sham and no-tinnitus animals but anti
      Hebbian modifications in noise-exposed animals with evidence for tinnitus. These
      findings suggest that stimulus-timing bimodal plasticity produced by the DCN
      circuitry is a contributing mechanism to enhanced central gain associated with
      tinnitus. 

PMID- 25392167
TI  - Postsynaptic mGluR5 promotes evoked AMPAR-mediated synaptic transmission onto
      neocortical layer 2/3 pyramidal neurons during development.
AB  - Both short- and long-term roles for the group I metabotropic glutamate receptor
      number 5 (mGluR5) have been examined for the regulation of cortical glutamatergic
      synapses. However, how mGluR5 sculpts neocortical networks during development
      still remains unclear. Using a single cell deletion strategy, we examined how
      mGluR5 regulates glutamatergic synaptic pathways in neocortical layer 2/3 (L2/3)
      during development. Electrophysiological measurements were made in acutely
      prepared slices to obtain a functional understanding of the effects stemming from
      loss of mGluR5 in vivo. Loss of postsynaptic mGluR5 results in an increase in the
      frequency of action potential-independent synaptic events but, paradoxically,
      results in a decrease in evoked transmission in two separate synaptic pathways
      providing input to the same pyramidal neurons. Synaptic transmission through
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but
      not N-methyl-d-aspartate (NMDA) receptors, is specifically decreased. In the
      local L2/3 pathway, the decrease in evoked transmission appears to be largely due
      to a decrease in cell-to-cell connectivity and not in the strength of individual
      cell-to-cell connections. This decrease in evoked transmission correlates with a
      decrease in the total dendritic length in a region of the dendritic arbor that
      likely receives substantial input from these two pathways, thereby suggesting a
      morphological correlate to functional alterations. These changes are accompanied
      by an increase in intrinsic membrane excitability. Our data indicate that total
      mGluR5 function, incorporating both short- and long-term processes, promotes the
      strengthening of AMPA receptor-mediated transmission in multiple neocortical
      pathways. 

PMID- 25392168
TI  - Related neuropeptides use different balances of unitary mechanisms to modulate
      the cardiac neuromuscular system in the American lobster, Homarus americanus.
AB  - To produce flexible outputs, neural networks controlling rhythmic motor behaviors
      can be modulated at multiple levels, including the pattern generator itself,
      sensory feedback, and the response of the muscle to a given pattern of motor
      output. We examined the role of two related neuropeptides, GYSDRNYLRFamide (GYS)
      and SGRNFLRFamide (SGRN), in modulating the neurogenic lobster heartbeat, which
      is controlled by the cardiac ganglion (CG). When perfused though an isolated
      whole heart at low concentrations, both peptides elicited increases in
      contraction amplitude and frequency. At higher concentrations, both peptides
      continued to elicit increases in contraction amplitude, but GYS caused a decrease
      in contraction frequency, while SGRN did not alter frequency. To determine the
      sites at which these peptides induce their effects, we examined the effects of
      the peptides on the periphery and on the isolated CG. When we removed the CG and
      stimulated the motor nerve with constant bursts of stimuli, both GYS and SGRN
      increased contraction amplitude, indicating that each peptide modulates the
      muscle or the neuromuscular junction. When applied to the isolated CG, neither
      peptide altered burst frequency at low peptide concentrations; at higher
      concentrations, SGRN decreased burst frequency, whereas GYS continued to have no
      effect on frequency. Together, these data suggest that the two peptides elicit
      some of their effects using different mechanisms; in particular, given the known
      feedback pathways within this system, the importance of the negative (nitric
      oxide) relative to the positive (stretch) feedback pathways may differ in the
      presence of the two peptides. 

PMID- 25392169
TI  - Role of neuronal nitric oxide synthase in the estrogenic attenuation of
      cannabinoid-induced changes in energy homeostasis.
AB  - Since estradiol attenuates cannabinoid-induced increases in energy intake, energy
      expenditure, and transmission at proopiomelanocortin (POMC) synapses in the
      hypothalamic arcuate nucleus (ARC), we tested the hypothesis that neuronal nitric
      oxide synthase (nNOS) plays an integral role. To this end, whole animal
      experiments were carried out in gonadectomized female guinea pigs. Estradiol
      benzoate (EB; 10 MUg sc) decreased incremental food intake as well as O2
      consumption, CO2 production, and metabolic heat production as early as 2 h
      postadministration. This was associated with increased phosphorylation of nNOS
      (pnNOS), as evidenced by an elevated ratio of pnNOS to nNOS in the ARC.
      Administration of the cannabinoid receptor agonist WIN 55,212-2 (3 MUg icv) into
      the third ventricle evoked hyperphagia as early as 1 h postadministration, which
      was blocked by EB and restored by the nonselective NOS inhibitor N-nitro-L
      arginine methyl ester hydrochloride (L-NAME; 100 MUg icv) when the latter was
      combined with the steroid. Whole cell patch-clamp recordings showed that 17beta
      estradiol (E2; 100 nM) rapidly diminished cannabinoid-induced decreases in
      miniature excitatory postsynaptic current frequency, which was mimicked by
      pretreatment with the NOS substrate L-arginine (30 MUM) and abrogated by L-NAME
      (300 MUM). Furthermore, E2 antagonized endocannabinoid-mediated depolarization
      induced suppression of excitation, which was nullified by the nNOS-selective
      inhibitor N5-[imino(propylamino)methyl]-L-ornithine hydrochloride (10 MUM). These
      effects occurred in a sizable number of identified POMC neurons. Taken together,
      the estradiol-induced decrease in energy intake is mediated by a decrease in
      cannabinoid sensitivity within the ARC feeding circuitry through the activation
      of nNOS. These findings provide compelling evidence for the need to develop
      rational, gender-specific therapies to help treat metabolic disorders such as
      cachexia and obesity.

PMID- 25392170
TI  - Localized adenosine signaling provides fine-tuned negative feedback over a wide
      dynamic range of neocortical network activities.
AB  - Although the patterns of activity produced by neocortical networks are now better
      understood, how these states are activated, sustained, and terminated still
      remains unclear. Negative feedback by the endogenous neuromodulator adenosine may
      potentially play an important role, as it can be released by activity and there
      is dense A1 receptor expression in the neocortex. Using electrophysiology,
      biosensors, and modeling, we have investigated the properties of adenosine
      signaling during physiological and pathological network activity in rat
      neocortical slices. Both low- and high-rate network activities were reduced by A1
      receptor activation and enhanced by block of A1 receptors, consistent with
      activity-dependent adenosine release. Since the A1 receptors were neither
      saturated nor completely unoccupied during either low- or high-rate activity,
      adenosine signaling provides a negative-feedback mechanism with a wide dynamic
      range. Modeling and biosensor experiments show that during high-rate activity
      increases in extracellular adenosine concentration are highly localized and are
      uncorrelated over short distances that are certainly<500 MUm. Modeling also
      predicts that the slow rise of the purine waveform cannot be from diffusion from
      distal release sites but more likely results from uptake and metabolism. The
      inability to directly measure adenosine release during low-rate activity,
      although it is present, is probably a consequence of small localized increases in
      adenosine concentration that are rapidly diminished by diffusion and active
      removal mechanisms. Saturation of such removal mechanisms when higher
      concentrations of adenosine are released results in the accumulation of inosine,
      explaining the strong purine signal during high-rate activity.

PMID- 25392171
TI  - Origins of basal ganglia output signals in singing juvenile birds.
AB  - Across species, complex circuits inside the basal ganglia (BG) converge on
      pallidal output neurons that exhibit movement-locked firing patterns. Yet the
      origins of these firing patterns remain poorly understood. In songbirds during
      vocal babbling, BG output neurons homologous to those found in the primate
      internal pallidal segment are uniformly activated in the tens of milliseconds
      prior to syllable onsets. To test the origins of this remarkably homogenous BG
      output signal, we recorded from diverse upstream BG cell types during babbling.
      Prior to syllable onsets, at the same time that internal pallidal segment-like
      neurons were activated, putative medium spiny neurons, fast spiking and tonically
      active interneurons also exhibited transient rate increases. In contrast,
      pallidal neurons homologous to those found in primate external pallidal segment
      exhibited transient rate decreases. To test origins of these signals, we
      performed recordings following lesion of corticostriatal inputs from premotor
      nucleus HVC. HVC lesions largely abolished these syllable-locked signals.
      Altogether, these findings indicate a striking homogeneity of syllable timing
      signals in the songbird BG during babbling and are consistent with a role for the
      indirect and hyperdirect pathways in transforming cortical inputs into BG outputs
      during an exploratory behavior. 

PMID- 25392172
TI  - Microstimulation of area V4 has little effect on spatial attention and on
      perception of phosphenes evoked in area V1.
AB  - Previous transcranial magnetic stimulation (TMS) studies suggested that feedback
      from higher to lower areas of the visual cortex is important for the access of
      visual information to awareness. However, the influence of cortico-cortical
      feedback on awareness and the nature of the feedback effects are not yet
      completely understood. In the present study, we used electrical microstimulation
      in the visual cortex of monkeys to test the hypothesis that cortico-cortical
      feedback plays a role in visual awareness. We investigated the interactions
      between the primary visual cortex (V1) and area V4 by applying microstimulation
      in both cortical areas at various delays. We report that the monkeys detected the
      phosphenes produced by V1 microstimulation but subthreshold V4 microstimulation
      did not influence V1 phosphene detection thresholds. A second experiment examined
      the influence of V4 microstimulation on the monkeys' ability to detect the
      dimming of one of three peripheral visual stimuli. Again, microstimulation of a
      group of V4 neurons failed to modulate the monkeys' perception of a stimulus in
      their receptive field. We conclude that conditions exist where microstimulation
      of area V4 has only a limited influence on visual perception. 

PMID- 25392173
TI  - The vision of Hsiao on somatosensation.
AB  - The goal of this review is to start to consolidate and distill the substantial
      body of research that comprises the published work of the late Professor Steven
      S. Hsiao. The studies of Hsiao began by demonstrating the receptive field
      properties of somatosensory neurons, progressed to describing cortical feature
      selectivity, and then eventually elevated the field to hopes of tapping into
      natural neural codes with artificial somatosensory feedback. With ongoing
      analogies to contemporaneous studies in visual neuroscience, the research results
      and writings of Hsiao have provided the fields of haptics and somatosensory
      neurophysiology with the conceptual tools needed to allow profound progress.
      Specifically, Hsiao suggested that slowly adapting tactile form perception could
      be restored with cortical microstimulation, rapidly adapting slip reflexes should
      be relegated to low-level, hard-wired prosthetic components, and Pacinian
      corpuscle spatiotemporal population responses could potentially be
      decoded/encoded to provide information about interactions of hands and hand-held
      instruments with external objects. Future studies will be guided by these
      insightful reports from Hsiao. 

PMID- 25392174
TI  - Early-onset cortico-cortical synchronization in the hemiparkinsonian rat model.
AB  - Changes in synchronized neuronal oscillatory activity are reported in both cortex
      and basal ganglia of Parkinson's disease patients. The origin of these changes,
      in particular their relationship with the progressive nigrostriatal dopaminergic
      denervation, is unknown. Therefore, in the present study we studied interregional
      neuronal synchronization in motor cortex and basal ganglia during the development
      of dopaminergic degeneration induced by a unilateral infusion of 6
      hydroxydopamine (6-OHDA) into the rat medial forebrain bundle. We performed
      serial local field potential recordings bilaterally in the motor cortex and the
      subthalamic nucleus of the lesioned hemisphere prior to, during, and after
      development of the nigrostriatal dopaminergic cell loss. We obtained signal from
      freely moving rats in both resting and walking conditions, and we computed local
      spectral power, interregional synchronization (using phase lag index), and
      directionality (using Granger causality). After neurotoxin injection the first
      change in phase lag index was an increment in cortico-cortical synchronization.
      We observed increased bidirectional Granger causality in the beta frequency band
      between cortex and subthalamic nucleus within the lesioned hemisphere. In the
      walking condition, the 6-OHDA lesion-induced changes in synchronization resembled
      that of the resting state, whereas the changes in Granger causality were less
      pronounced after the lesion. Considering the relatively preserved connectivity
      pattern of the cortex contralateral to the lesioned side and the early emergence
      of increased cortico-cortical synchronization during development of the 6-OHDA
      lesion, we suggest a putative compensatory role of cortico-cortical coupling. 

PMID- 25392175
TI  - Hedgehog pathway blockade with the cancer drug LDE225 disrupts taste organs and
      taste sensation.
AB  - Taste sensation on the anterior tongue requires chorda tympani nerve function and
      connections with continuously renewing taste receptor cells. However, it is
      unclear which signaling pathways regulate the receptor cells to maintain chorda
      tympani sensation. Hedgehog (HH) signaling controls cell proliferation and
      differentiation in numerous tissues and is active in taste papillae and taste
      buds. In contrast, uncontrolled HH signaling drives tumorigenesis, including the
      common skin cancer, basal cell carcinoma. Systemic HH pathway inhibitors (HPIs)
      lead to basal cell carcinoma regression, but these drugs cause severe taste
      disturbances. We tested the hypothesis that taste disruption by HPIs reflects a
      direct requirement for HH signaling in maintaining taste organs and gustatory
      sensation. In mice treated with the HPI LDE225 up to 28 days, HH-responding cells
      were lost in fungiform papilla epithelium, and papillae acquired a conical apex.
      Taste buds were either absent or severely reduced in size in more than 90% of
      aberrant papillae. Taste bud remnants expressed the taste cell marker keratin 8,
      and papillae retained expression of nerve markers, neurofilament and P2X3. Chorda
      tympani nerve responses to taste stimuli were markedly reduced or absent in
      LDE225-treated mice. Responses to touch were retained, however, whereas cold
      responses were retained after 16 days of treatment but lost after 28 days. These
      data identify a critical, modality-specific requirement for HH signaling in
      maintaining taste papillae, taste buds and neurophysiological taste function,
      supporting the proposition that taste disturbances in HPI-treated patients are an
      on-target response to HH pathway blockade in taste organs. 

PMID- 25392177
TI  - SIK1 localizes with nephrin in glomerular podocytes and its polymorphism predicts
      kidney injury.

PMID- 25392176
TI  - Neocortical inhibitory activities and long-range afferents contribute to the
      synchronous onset of silent states of the neocortical slow oscillation.
AB  - During slow-wave sleep, neurons of the thalamocortical network are engaged in a
      slow oscillation (<1 Hz), which consists of an alternation between the active and
      the silent states. Several studies have provided insights on the transition from
      the silent, which are essentially periods of disfacilitation, to the active
      states. However, the conditions leading to the synchronous onset of the silent
      state remain elusive. We hypothesized that a synchronous input to local
      inhibitory neurons could contribute to the transition to the silent state in the
      cat suprasylvian gyrus during natural sleep and under ketamine-xylazine
      anesthesia. After partial and complete deafferentation of the cortex, we found
      that the silent state onset was more variable among remote sites. We found that
      the transition to the silent state was preceded by a reduction in excitatory
      postsynaptic potentials and firing probability in cortical neurons. We tested the
      impact of chloride-mediated inhibition in the silent-state onset. We uncovered a
      long-duration (100-300 ms) inhibitory barrage occurring about 250 ms before the
      silent state onset in 3-6% of neurons during anesthesia and in 12-15% of cases
      during natural sleep. These inhibitory activities caused a decrease in cortical
      firing that reduced the excitatory drive in the neocortical network. That chain
      reaction of disfacilitation ends up on the silent state. Electrical stimuli could
      trigger a network silent state with a maximal efficacy in deep cortical layers.
      We conclude that long-range afferents to the neocortex and chloride-mediated
      inhibition play a role in the initiation of the silent state. 

PMID- 25392178
TI  - Uncertainties about medical treatment of acute heart failure.

PMID- 25392179
TI  - Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their
      correlation with molecular cancer type.
AB  - Cancer cells expressing PD-1 ligands (PD-L1/PD-L2) inhibit immune-modulatory T
      cell activation facilitating disease progression. Preliminary clinical trials
      exploring interruption of PD-1/PD-L1 signaling showed benefit in several cancer
      types. We analyzed the distribution of PD-1-positive tumor-infiltrating
      lymphocytes (TIL) and cancer cells' expression of PD-L1 in a molecularly profiled
      cohort of 437 malignancies (380 carcinomas, 33 sarcomas, and 24 melanomas). We
      showed that the presence of PD-1(+) TILs significantly varied among cancer types
      (from 0% in extraskeletal myxoid chondrosarcomas to 93% in ovarian cancer), and
      was generally associated with the increased number of mutations in tumor cells (P
      = 0.029). Cancer cell expression of PD-L1 varied from absent (in Merkel cell
      carcinomas) to 100% (in chondro- and liposarcomas), but showed the inverse
      association with the number of detected mutations (P = 0.004). Both PD-1 and PD
      L1 expression were significantly higher in triple-negative breast cancers (TNBC)
      than in non-TNBC (P < 0.001 and 0.017, respectively). Similarly, MSI-H colon
      cancers had higher PD-1 and PD-L1 expression than the microsatellite stable
      tumors (P = 0.002 and 0.02, respectively). TP53-mutated breast cancers had
      significantly higher PD-1 positivity than those harboring other driver mutations
      (e.g., PIK3CA; P = 0.002). In non-small cell lung cancer, PD-1/PD-L1 coexpression
      was identified in 8 cases (19%), which lacked any other targetable alterations
      (e.g., EGFR, ALK, or ROS1). Our study demonstrated the utility of exploring the
      expression of two potentially targetable immune checkpoint proteins (PD-1/PD-L1)
      in a substantial proportion of solid tumors, including some aggressive subtypes
      that lack other targeted treatment modalities.

PMID- 25392180
TI  - Sexual transmission of oral human papillomavirus infection among men.
AB  - We estimated the prevalence of oral human papillomavirus (HPV) and assessed risk
      factors among young heterosexual men participating in the HPV Infection and
      Transmission among Couples through Heterosexual Activity (HITCH) study. Oral and
      genital HPV samples were collected from 222 men and their female partners who
      were participating in the HITCH study, a longitudinal cohort on HPV transmission
      among heterosexual couples. Demographic and behavioral data were collected
      through self-administered computer questionnaires and biologic samples were
      tested with the Linear Array for HPV. Outcome measures were overall and type
      specific prevalence of oral HPV. The prevalence of oral HPV among men was 7.2%
      and was higher among men who were ever smokers (12.2%), in nonmonogamous
      relationships (17.9%), or had a partner with oral (28.6%) and/or genital (11.5%)
      HPV infection. Moreover, prevalence increased with frequency of oral sex among
      men whose partner who had a genital infection with the same HPV type. Our results
      provide further evidence that oral HPV may be transmitted through either oral
      oral or oral-genital routes.

PMID- 25392181
TI  - Identification and diagnostic performance of a small RNA within the PCA3 and
      BMCC1 gene locus that potentially targets mRNA.
AB  - BACKGROUND: PCA3 is a long noncoding RNA (lncRNA) with unknown function,
      upregulated in prostate cancer. LncRNAs may be processed into smaller active
      species. We hypothesized this for PCA3. METHODS: We computed feasible RNA
      hairpins within the BMCC1 gene (encompassing PCA3) and searched a prostate
      transcriptome for these. We measured expression using qRT-PCR in three cohorts of
      prostate cancer tissues (n = 60), exfoliated urinary cells (n = 484 with cancer
      and n = 166 controls), and in cell lines (n = 22). We used in silico predictions
      and RNA knockup to identify potential mRNA targets of short transcribed RNAs.
      RESULTS: We predicted 13 hairpins, of which PCA3-shRNA2 was most abundant within
      the prostate transcriptome. PCA3-shRNA2 is located within intron 1 of PCA3 and
      appears regulated by androgens. Expression of PCA3-shRNA2 was upregulated in
      malignant prostatic tissues, exfoliated urinary cells from men with prostate
      cancer (13-273 fold change; t test P < 0.003), and closely correlated to PCA3
      expression (r = 0.84-0.93; P < 0.001). Urinary PCA3-shRNA2 (C-index, 0.75-0.81)
      and PCA3 (C-index, 0.78) could predict the presence of cancer in most men. PCA3
      shRNA2 knockup altered the expression of predicted target mRNAs, including COPS2,
      SOX11, WDR48, TEAD1, and Noggin. PCA3-shRNA2 expression was negatively correlated
      with COPS2 in patient samples (r = -0.32; P < 0.001). CONCLUSION: We identified a
      short RNA within PCA3, whose expression is correlated to PCA3, which may target
      mRNAs implicated in prostate biology. IMPACT: This short RNA is stable ex vivo,
      suggesting a role as a robust biomarker. We identify cytoplasmic enrichment of
      this RNA and potential targeting of mRNAs implicated in prostate carcinogenesis.

PMID- 25392182
TI  - Difference in prognostic values of maximal standardized uptake value on
      fluorodeoxyglucose-positron emission tomography and cyclooxygenase-2 expression
      between lung adenocarcinoma and squamous cell carcinoma.
AB  - BACKGROUND: The maximal standardized uptake value (SUVmax) on fluorodeoxyglucose
      positron emission tomography (FDG-PET) for primary tumors is correlated with
      clinicopathological and prognostic factors in patients with non-small cell lung
      cancer. However, previous investigations have discussed the role of SUVmax
      without distinguishing among the histological subtypes of lung cancer. Herein, we
      investigated the correlations among the SUVmax on FDG-PET, clinicopathological or
      prognostic factors, and the expression of tumor angiogenic biomarkers according
      to histological subtypes. METHODS: We conducted a retrospective review of data
      from 52 patients with invasive adenocarcinoma (ADC) and 32 patients with squamous
      cell carcinoma (SQC) measuring less than 3 cm in diameter. Immunohistochemical
      staining for cyclooxygenase-2 (Cox-2), Ki-67, and vascular endothelial growth
      factor, which might influence cancer progression, was performed and the
      correlations between the expressions of these biomarkers and the SUVmax were
      evaluated. RESULTS: Among ADC patients, a statistically significant correlation
      was observed between the SUVmax and the major clinicopathological factors; among
      SQC patients, however, no statistically significant association was observed. The
      disease-free survival (DFS) period of the ADC patients with a high SUVmax was
      significantly poorer than that of the patients with a low SUVmax, but the DFS of
      the SQC patients with a high SUVmax was not significantly poorer. In a
      multivariate analysis, the pathological stage and the SUVmax were independent
      prognostic factors of the DFS among the ADC patients. Among the SQC patients,
      however, only Cox-2 expression was an independent prognostic factor of DFS.
      CONCLUSIONS: Some clear differences in prognostic values of the SUVmax on FDG-PET
      and Cox-2 expression exist between patients with ADC and those with SQC. Based on
      these relationships between the SUVmax and clinicopathological or biological
      factors that influence cancer progression, the importance of the SUVmax appears
      to be quite different for patients with ADC and those with SQC.

PMID- 25392183
TI  - Vaginal estrogen use in postmenopausal women with pelvic floor disorders:
      systematic review and practice guidelines.
AB  - INTRODUCTION AND HYPOTHESIS: Risk of pelvic floor disorders increases after
      menopause and may be linked to estrogen deficiency. We aimed to systematically
      and critically assess the literature on vaginal estrogen in the management of
      pelvic floor disorders in postmenopausal women and provide evidence-based
      clinical practice guidelines. METHODS: MEDLINE and Cochrane databases were
      searched from inception to July 2014 for randomized controlled trials of
      commercially available vaginal estrogen products compared with placebo, no
      treatment, or any medication for overactive bladder or urinary incontinence. We
      double-screened 1,805 abstracts and identified 12 eligible papers. Studies were
      extracted for participant information, intervention, comparator, efficacy
      outcomes, and adverse events, and they were individually and collectively
      assessed for methodological quality and strength of evidence. RESULTS: Evidence
      was generally of poor to moderate quality. Vaginal estrogen application before
      pelvic organ prolapse surgery improved the vaginal maturation index and increased
      vaginal epithelial thickness. Postoperative vaginal estrogen use after a
      midurethral sling resulted in decreased urinary frequency and urgency. Vaginal
      estrogen and immediate-release oxybutynin were similar in improvement of urinary
      urgency, frequency, and urgency urinary incontinence in women with overactive
      bladder, but oxybutynin had higher rates of side effects and discontinuation.
      Conversely, the addition of vaginal estrogen to immediate or extended-release
      tolterodine did not improve urinary symptoms more than tolterodine alone. One
      study reported an improvement in stress urinary incontinence with use of vaginal
      estrogen. CONCLUSION: Vaginal estrogen application may play a useful role as an
      adjunct in the management of common pelvic floor disorders in postmenopausal
      women.

PMID- 25392184
TI  - Sexual function in women with anal incontinence using a new instrument: the PISQ
      IR.
AB  - INTRODUCTION: Anal incontinence (AI) has been associated with sexual complaints.
      The Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA Revised (PISQ
      IR) has been validated to measure sexual function in sexually active (SA) and non
      SA (NSA) women with pelvic floor disorders (PFD) including AI. We describe
      symptoms in women with PFDs including AI using this instrument. METHODS: This was
      a planned secondary analysis of data collected for the validation of the PISQ-IR.
      SA and NSA women with symptoms of pelvic organ prolapse, urinary incontinence
      (UI) and/or AI at 12 US and 5 UK sites were recruited. The Female Sexual Function
      Index (FSFI) and PISQ-IR were completed in addition to the Pelvic Floor Distress
      Inventory (PFDI), and other measures. RESULTS: Of 872 women enrolled, 90 (10%)
      reported AI. Compared with women without AI, women with AI were more likely to
      report stress UI (p = 0.007), urgency UI (p < 0.001), mixed UI (p < 0.001),
      diabetes (p = 0.036) and depression (p < 0.001), and to show larger genital
      hiatus measurements (p = 0.005) and more underactive pelvic floor muscles (p =
      0.011). Furthermore, scores on the PFDI showed greater bother (p = 0.013),
      particularly the colorectal subscale (p < 0.001). While sexual activity was
      similar between the groups, FSFI desire (p = 0.016), PISQ-IR 'condition-specific'
      (p = 0.03) and 'global quality' (p = 0.046) domains were worse in women with AI.
      In logistic regression analysis, only the PISQ-IR 'condition-specific' domain was
      associated with AI when controlling for other confounders (OR 0.27, 95% CI 0.10 -
      0.72, p = 0.009). CONCLUSIONS: Women with AI have similar rates of sexual
      activity but poorer sexual function than women without AI. The PISQ-IR may be
      most appropriate to characterize these conditions.

PMID- 25392185
TI  - Authors' reply to Dalzell and Cannon and Satchithananda and colleagues.

PMID- 25392186
TI  - Identification of edible Bird's nest with amino acid and monosaccharide analysis.
AB  - This study describes the approach of amino acid and monosaccharide combined with
      Hotelling T2 range plot to identify edible bird nests (EBN) and non-EBN. Prior to
      the approach, an analytical method was developed and validated to quantify
      monosaccharides in EBN. Hotelling T2 range plots of both compounds were
      successful in predicting the different types of EBN and differentiating EBN and
      non-EBN. This outcome suggests EBN contains a group of glycoproteins which is not
      affected by the EBN's coloration, country of origin, and/or the processing method
      of the food item. In addition, the glycoproteins were shown to be unique to EBN.
      EBN were revealed to be rich in protein and essential amino acids as well as
      contain a wider variety of monosaccharides than most food items. The overall
      findings suggest that amino acid and monosaccharide provide information not only
      on the detected compounds and also insights into the glycoproteins of EBN.

PMID- 25392187
TI  - Testosterone treatment of men with mild cognitive impairment and low testosterone
      levels.
AB  - INTRODUCTION: This study investigated the effects of testosterone (T) treatment
      on cognition, mood, and quality of life in men with mild cognitive impairment
      (MCI) and low serum T levels. METHODS: A total of 351 community-dwelling men were
      screened, and 37 men evidenced both MCI and low T of whom 27 agreed for further
      screening. Twenty-two met all the study inclusion/exclusion criteria and enrolled
      in a 6-month randomized, double-blind, placebo-controlled study. RESULTS: Total T
      levels significantly increased in the T treatment group. No significant changes
      were observed in measures of cognition, mood, or quality of life other than
      improvement in 1 objective measure of verbal memory (P < .05) and decreased
      depression symptoms (P < .02) in the treatment group. CONCLUSIONS: Testosterone
      treatment may modestly improve verbal memory and depression symptoms in men with
      both MCI and low T.

PMID- 25392188
TI  - Host tree phenology affects vascular epiphytes at the physiological, demographic
      and community level.
AB  - The processes that govern diverse tropical plant communities have rarely been
      studied in life forms other than trees. Structurally dependent vascular
      epiphytes, a major part of tropical biodiversity, grow in a three-dimensional
      matrix defined by their hosts, but trees differ in their architecture, bark
      structure/chemistry and leaf phenology. We hypothesized that the resulting
      seasonal differences in microclimatic conditions in evergreen vs. deciduous trees
      would affect epiphytes at different levels, from organ physiology to community
      structure. We studied the influence of tree leaf phenology on vascular epiphytes
      on the Island of Barro Colorado, Panama. Five tree species were selected, which
      were deciduous, semi-deciduous or evergreen. The crowns of drought-deciduous
      trees, characterized by sunnier and drier microclimates, hosted fewer individuals
      and less diverse epiphyte assemblages. Differences were also observed at a
      functional level, e.g. epiphyte assemblages in deciduous trees had larger
      proportions of Crassulacean acid metabolism species and individuals. At the
      population level a drier microclimate was associated with lower individual growth
      and survival in a xerophytic fern. Some species also showed, as expected, lower
      specific leaf area and higher delta(13)C values when growing in deciduous trees
      compared with evergreen trees. As hypothesized, host tree leaf phenology
      influences vascular epiphytes at different levels. Our results suggest a
      cascading effect of tree composition and associated differences in tree phenology
      on the diversity and functioning of epiphyte communities in tropical lowland
      forests. 

PMID- 25392189
TI  - Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA
      methylation profiles.
AB  - Maternal one-carbon (1-C) metabolism provides methylgroups for fetal development
      and programing by DNA methylation as one of the underlying epigenetic mechanisms.
      We aimed to investigate maternal 1-C biomarkers, folic acid supplement use, and
      MTHFR C677T genotype as determinants of 1-C metabolism in early pregnancy in
      association with newborn DNA methylation levels of fetal growth and
      neurodevelopment candidate genes. The participants were 463 mother-child pairs of
      Dutch national origin from a large population-based birth cohort in Rotterdam,
      The Netherlands. In early pregnancy (median 13.0 weeks, 90% range 10.4-17.1), we
      assessed the maternal folate and homocysteine blood concentrations, folic acid
      supplement use, and the MTHFR C677T genotype in mothers and newborns. In
      newborns, DNA methylation was measured in umbilical cord blood white blood cells
      at 11 regions of the seven genes: NR3C1, DRD4, 5-HTT, IGF2DMR, H19, KCNQ1OT1, and
      MTHFR. The associations between the 1-C determinants and DNA methylation were
      examined using linear mixed models. An association was observed between maternal
      folate deficiency and lower newborn DNA methylation, which attenuated after
      adjustment for potential confounders. The maternal MTHFR TT genotype was
      significantly associated with lower DNA methylation. However, maternal
      homocysteine and folate concentrations, folic acid supplement use, and the MTHFR
      genotype in the newborn were not associated with newborn DNA methylation. The
      maternal MTHFR C677T genotype, as a determinant of folate status and 1-C
      metabolism, is associated with variations in the epigenome of a selection of
      genes in newborns. Research on the implications of these variations in
      methylation on gene expression and health is recommended. 

PMID- 25392190
TI  - ADAM15 participates in fertilization through a physical interaction with
      acrogranin.
AB  - Mammalian fertilization is completed by direct interaction between sperm and egg.
      This process is primarily mediated by both adhesion and membrane-fusion proteins
      found on the gamete surface. ADAM1, 2, and 3 are members of the ADAMs protein
      family, and have been involved in sperm-egg binding. In this study, we
      demonstrate the proteolytic processing of ADAM15 during epididymal maturation of
      guinea pig spermatozoa to produce a mature form a size of 45 kDa. We find that
      the size of the mature ADAM15, 45 kDa, in cauda epididymal spermatozoa indicates
      that the pro-domain and metalloprotease domain are absent. In addition, using
      indirect immunofluorescence, ADAM15 was found throughout the acrosome, at the
      equatorial region and along the flagellum of guinea pig spermatozoa. After
      acrosome reaction, ADAM15 is lost from the acrosomal region and retained in the
      equatorial region and flagellum. In this study, we also report the first evidence
      of a complex between ADAM15 and acrogranin. By immunoprecipitation, we detected a
      protein band of 65 kDa which co-immunoprecipated together ADAM15. Analysis of the
      N-terminal sequence of this 65 kDa protein has revealed its identity as
      acrogranin. In addition, using cell-surface labeling, ADAM15 was found to be
      present on the cell surface. Assays of heterologous fertilization showed that the
      antibody against acrogranin inhibited the sperm-egg adhesion. Interestingly,
      ADAM15 and acrogranin were also found associated in two breast cancer cell lines.
      In conclusion, our results demonstrated that ADAM15 and acrogranin are present on
      and associated with the surface of guinea pig spermatozoa; besides both proteins
      may play a role during sperm-egg binding.

PMID- 25392191
TI  - Environmental factors and childhood Fever in areas of the Ouagadougou Health and
      Demographic Surveillance System, Burkina Faso.
AB  - Using data on 825 under-5 children from the Ouagadougou Health and Demographic
      Surveillance System collected in 2010, this article examines the effects of
      aspects of the immediate environment on childhood fever. Logit regression models
      were estimated to assess the effects of the quality of the local environment on
      the probability that a child is reported to have had a fever in the two weeks
      preceding the survey, after controlling for various demographic and socioeconomic
      variables. While the estimated impact of some environmental factors persisted in
      the full models, the effects of variables such as access to water and type of
      household waste management decreased in the presence of demographic,
      socioeconomic and neighbourhood factors. The management of waste water was found
      to significantly affect the occurrence of childhood fever. Overall, the results
      of the study call for more efforts to promote access to tap water to households
      at prices that are affordable for the local population, where the threats to
      child health appears to be greatest. 

PMID- 25392192
TI  - Retrieval-induced forgetting of multiplication facts and identity rule.
AB  - This research investigated retrieval-induced interference between counterpart
      multiplication (2 * 3 = 6) and addition facts (2 + 3 = 5). Adults (N =72)
      repeatedly solved either a set of simple addition (0 + 2, 1 + 5, 2 + 3) or
      multiplication problems (0 * 2, 1 * 5, 2 * 3) during a practice phase and then
      switched operations during a test phase that included counterparts to the
      practiced problems and control problems. The paradigm afforded measurement in
      response time both of inter-operation retrieval-induced forgetting (RIF) and
      generalization of practice across different problems within operations. The
      experiment demonstrated generalization of practice for the rule-based 0 + N = N
      problems (e.g., practicing 0 + 2 facilitated performance on 0 + 7) as well as for
      problems governed by the multiplicative identity principle (1 * N = N) and zero
      product principle (0 * N = 0), but not the fact-based 1 + N problems. The
      experiment also demonstrated for the first time inter-operation RIF of fact-based
      multiplication, which was as large as the effect observed for fact-based
      addition. The 0 * N, 0 + N, and 1 + N problems did not present item-specific RIF
      from practice of cross-operation counterparts, but 1 * N problems did, despite
      the generalization-of-practice evidence that 1 * N problems were solved using an
      item-general procedure. The item-specific RIF for 1 * N = N must reflect item
      specific interference rather than item-level competitor inhibition given that
      there is no item-level representation of 1 * N = N facts in long-term memory.

PMID- 25392193
TI  - Pro Re Nata Intravitreal Bevacizumab for the Treatment of Idiopathic Choroidal
      Neovascular Membrane.
AB  - PURPOSE: To study the efficacy of intravitreal bevacizumab on a pro re nata basis
      for treatment of idiopathic choroidal neovascular membrane. MATERIAL AND METHODS:
      Thirty-seven eyes of 37 patients presenting with idiopathic choroidal neovascular
      membrane were included in the study. Intravitreal bevacizumab (1.25 mg/0.05 ml)
      was given on a pro re nata basis from the base line. RESULTS: Twenty-one (58.3%)
      patients were male and 15 (41.7%) were female aged 13-49 years. Idiopathic
      choroidal neovascular membrane showed a classic leak on fluorescein angiogram in
      all the eyes. Subfoveal location (25; 67.6%) was the commonest site of
      involvement. Mean number of intravitreal bevacizumab injections required to
      achieve resolution was 2.81 +/- 1.4. At final follow-up, 31 (83.8%) eyes had
      maintained or improved vision (Group A) and six (16.2%) eyes had worsening of
      vision (Group B). There was no significant difference in mean age, gender, and
      mean number of injections between groups A and B. CONCLUSION: Intravitreal
      bevacizumab on a pro re nata basis is effective in the treatment of idiopathic
      choroidal neovascular membrane. A larger controlled study would be required to
      formulate an accurate injection protocol.

PMID- 25392194
TI  - Combined associations of genetic and environmental risk factors: implications for
      prevention of breast cancer.
AB  - Genome-wide association studies (GWAS) have identified hundreds of genetic
      susceptibility loci for cancers and other complex diseases. However, the public
      health and clinical relevance of these discoveries is unclear. Evaluating the
      combined associations of genetic and environmental risk factors, particularly
      those that can be modified, will be critical in assessing the utility of genetic
      information for risk stratified prevention. In this commentary, using breast
      cancer as a model, we show that genetic information in combination with other
      risk factors can provide levels of risk stratification that could be useful for
      individual decision-making or population-based prevention programs. Our
      projections are theoretical and rely on a number of assumptions, including
      multiplicative models for the combined associations of the different risk
      factors, which need confirmation. Thus, analyses of epidemiological studies with
      high-quality risk factor information, as well as prevention trials, are needed to
      empirically assess the impact of genetics in risk stratified prevention.

PMID- 25392196
TI  - Altered structural connectivity of cortico-striato-pallido-thalamic networks in
      Gilles de la Tourette syndrome.
AB  - Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the
      presence and persistence of motor and vocal tics. A dysfunction of cortico
      striato-pallido-thalamo-cortical networks in this syndrome has been supported by
      convergent data from neuro-pathological, electrophysiological as well as
      structural and functional neuroimaging studies. Here, we addressed the question
      of structural integration of cortico-striato-pallido-thalamo-cortical networks in
      Gilles de la Tourette syndrome. We specifically tested the hypothesis that
      deviant brain development in Gilles de la Tourette syndrome could affect
      structural connectivity within the input and output basal ganglia structures and
      thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and
      age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used
      and further implemented streamline probabilistic tractography algorithms that
      allowed us to quantify the structural integration of cortico-striato-pallido
      thalamo-cortical networks. To further investigate the microstructure of white
      matter in patients with Gilles de la Tourette syndrome, we also evaluated
      fractional anisotropy and radial diffusivity in these pathways, which are both
      sensitive to axonal package and to myelin ensheathment. In patients with Gilles
      de la Tourette syndrome compared to control subjects, we found white matter
      abnormalities in neuronal pathways connecting the cerebral cortex, the basal
      ganglia and the thalamus. Specifically, striatum and thalamus had abnormally
      enhanced structural connectivity with primary motor and sensory cortices, as well
      as paracentral lobule, supplementary motor area and parietal cortices. This
      enhanced connectivity of motor cortex positively correlated with severity of tics
      measured by the Yale Global Tics Severity Scale and was not influenced by current
      medication status, age or gender of patients. Independently of the severity of
      tics, lateral and medial orbito-frontal cortex, inferior frontal, temporo
      parietal junction, medial temporal and frontal pole also had enhanced structural
      connectivity with the striatum and thalamus in patients with Gilles de la
      Tourette syndrome. In addition, the cortico-striatal pathways were characterized
      by elevated fractional anisotropy and diminished radial diffusivity, suggesting
      microstructural axonal abnormalities of white matter in Gilles de la Tourette
      syndrome. These changes were more prominent in females with Gilles de la Tourette
      syndrome compared to males and were not related to the current medication status.
      Taken together, our data showed widespread structural abnormalities in cortico
      striato-pallido-thalamic white matter pathways in patients with Gilles de la
      Tourette, which likely result from abnormal brain development in this syndrome. 

PMID- 25392197
TI  - Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of
      diabetes.
AB  - Treatment-induced neuropathy in diabetes (also referred to as insulin neuritis)
      is considered a rare iatrogenic small fibre neuropathy caused by an abrupt
      improvement in glycaemic control in the setting of chronic hyperglycaemia. The
      prevalence and risk factors of this disorder are not known. In a retrospective
      review of all individuals referred to a tertiary care diabetic neuropathy clinic
      over 5 years, we define the proportion of individuals that present with and the
      risk factors for development of treatment-induced neuropathy in diabetes. Nine
      hundred and fifty-four individuals were evaluated for a possible diabetic
      neuropathy. Treatment-induced neuropathy in diabetes was defined as the acute
      onset of neuropathic pain and/or autonomic dysfunction within 8 weeks of a large
      improvement in glycaemic control-specified as a decrease in glycosylated
      haemoglobin A1C (HbA1c) of >=2% points over 3 months. Detailed structured
      neurologic examinations, glucose control logs, pain scores, autonomic symptoms
      and other microvascular complications were measured every 3-6 months for the
      duration of follow-up. Of 954 patients evaluated for diabetic neuropathy, 104/954
      subjects (10.9%) met criteria for treatment-induced neuropathy in diabetes with
      an acute increase in neuropathic or autonomic symptoms or signs coinciding with a
      substantial decrease in HbA1c. Individuals with a decrease in HbA1c had a much
      greater risk of developing a painful or autonomic neuropathy than those
      individuals with no change in HbA1c (P < 0.001), but also had a higher risk of
      developing retinopathy (P < 0.001) and microalbuminuria (P < 0.001). There was a
      strong correlation between the magnitude of decrease in HbA1c, the severity of
      neuropathic pain (R = 0.84, P < 0.001), the degree of parasympathetic dysfunction
      (R = -0.52, P < 0.01) and impairment of sympathetic adrenergic function as
      measured by fall in blood pressure on tilt-table testing (R = -0.63, P < 0.001).
      With a decrease in HbA1c of 2-3% points over 3 months there was a 20% absolute
      risk of developing treatment-induced neuropathy in diabetes, with a decrease in
      HbA1c of >4% points over 3 months the absolute risk of developing treatment
      induced neuropathy in diabetes exceeded 80%. Treatment-induced neuropathy of
      diabetes is an underestimated iatrogenic disorder associated with diffuse
      microvascular complications. Rapid glycaemic change in patients with uncontrolled
      diabetes increases the risk of this complication. 

PMID- 25392198
TI  - Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in
      mice.
AB  - Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe
      neuropsychiatric disorder that associates with prominent memory and behavioural
      deficits. Patients' antibodies react with the N-terminal domain of the GluN1
      (previously known as NR1) subunit of NMDAR causing in cultured neurons a
      selective and reversible internalization of cell-surface receptors. These effects
      and the frequent response to immunotherapy have suggested an antibody-mediated
      pathogenesis, but to date there is no animal model showing that patients'
      antibodies cause memory and behavioural deficits. To develop such a model,
      C57BL6/J mice underwent placement of ventricular catheters connected to osmotic
      pumps that delivered a continuous infusion of patients' or control cerebrospinal
      fluid (flow rate 0.25 ul/h, 14 days). During and after the infusion period
      standardized tests were applied, including tasks to assess memory (novel object
      recognition in open field and V-maze paradigms), anhedonic behaviours (sucrose
      preference test), depressive-like behaviours (tail suspension, forced swimming
      tests), anxiety (black and white, elevated plus maze tests), aggressiveness
      (resident-intruder test), and locomotor activity (horizontal and vertical).
      Animals sacrificed at Days 5, 13, 18, 26 and 46 were examined for brain-bound
      antibodies and the antibody effects on total and synaptic NMDAR clusters and
      protein concentration using confocal microscopy and immunoblot analysis. These
      experiments showed that animals infused with patients' cerebrospinal fluid, but
      not control cerebrospinal fluid, developed progressive memory deficits, and
      anhedonic and depressive-like behaviours, without affecting other behavioural or
      locomotor tasks. Memory deficits gradually worsened until Day 18 (4 days after
      the infusion stopped) and all symptoms resolved over the next week. Accompanying
      brain tissue studies showed progressive increase of brain-bound human antibodies,
      predominantly in the hippocampus (maximal on Days 13-18), that after acid
      extraction and characterization with GluN1-expressing human embryonic kidney
      cells were confirmed to be against the NMDAR. Confocal microscopy and immunoblot
      analysis of the hippocampus showed progressive decrease of the density of total
      and synaptic NMDAR clusters and total NMDAR protein concentration (maximal on Day
      18), without affecting the post-synaptic density protein 95 (PSD95) and alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. These
      effects occurred in parallel with memory and other behavioural deficits and
      gradually improved after Day 18, with reversibility of symptoms accompanied by a
      decrease of brain-bound antibodies and restoration of NMDAR levels. Overall,
      these findings establish a link between memory and behavioural deficits and
      antibody-mediated reduction of NMDAR, provide the biological basis by which
      removal of antibodies and antibody-producing cells improve neurological function,
      and offer a model for testing experimental therapies in this and similar
      disorders. 

PMID- 25392200
TI  - Paediatric epilepsy surgery: making the best of a tough situation.

PMID- 25392199
TI  - Temporal lobe surgery in childhood and neuroanatomical predictors of long-term
      declarative memory outcome.
AB  - The temporal lobes play a prominent role in declarative memory function,
      including episodic memory (memory for events) and semantic memory (memory for
      facts and concepts). Surgical resection for medication-resistant and well
      localized temporal lobe epilepsy has good prognosis for seizure freedom, but is
      linked to memory difficulties in adults, especially when the removal is on the
      left side. Children may benefit most from surgery, because brain plasticity may
      facilitate post-surgical reorganization, and seizure cessation may promote
      cognitive development. However, the long-term impact of this intervention in
      children is not known. We examined memory function in 53 children (25 males, 28
      females) who were evaluated for epilepsy surgery: 42 underwent unilateral
      temporal lobe resections (25 left, 17 right, mean age at surgery 13.8 years), 11
      were treated only pharmacologically. Average follow-up was 9 years (range 5-15).
      Post-surgical change in visual and verbal episodic memory, and semantic memory at
      follow-up were examined. Pre- and post-surgical T1-weighted MRI brain scans were
      analysed to extract hippocampal and resection volumes, and evaluate post-surgical
      temporal lobe integrity. Language lateralization indices were derived from
      functional magnetic resonance imaging. There were no significant pre- to
      postoperative decrements in memory associated with surgery. In contrast, gains in
      verbal episodic memory were seen after right temporal lobe surgery, and visual
      episodic memory improved after left temporal lobe surgery, indicating a
      functional release in the unoperated temporal lobe after seizure reduction or
      cessation. Pre- to post-surgical change in memory function was not associated
      with any indices of brain structure derived from MRI. However, better verbal
      memory at follow-up was linked to greater post-surgical residual hippocampal
      volumes, most robustly in left surgical participants. Better semantic memory at
      follow-up was associated with smaller resection volumes and greater temporal pole
      integrity after left temporal surgery. Results were independent of post-surgical
      intellectual function and language lateralization. Our findings indicate post
      surgical, hemisphere-dependent material-specific improvement in memory functions
      in the intact temporal lobe. However, outcome was linked to the anatomical
      integrity of the temporal lobe memory system, indicating that compensatory
      mechanisms are constrained by the amount of tissue which remains in the operated
      temporal lobe. Careful tailoring of resections for children undergoing epilepsy
      surgery may enhance long-term memory outcome. 

PMID- 25392201
TI  - Question 2: Does the timing of central line placement in relationship to the
      initiation of acute lymphoblastic leukaemia therapy change the risk of thrombosis
      or infection?

PMID- 25392202
TI  - Erythropoietic protoporphyria in a boy.

PMID- 25392203
TI  - Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment
      of Parkinson's disease by reducing oxidative stress.
AB  - Resveratrol, a potent natural antioxidant, possesses a wide range of
      pharmacological activities, but its oral bioavailability is very low due to its
      extensive hepatic and presystemic metabolism. The aim of the present study was to
      formulate a kinetically stable nanoemulsion (o/w) using vitamin E:sefsol (1:1) as
      the oil phase, Tween 80 as the surfactant and Transcutol P as the co-surfactant
      for the better management of Parkinson's disease. The nanoemulsion was prepared
      by a spontaneous emulsification method, followed by high-pressure homogenization.
      Ternary phase diagrams were constructed to locate the area of nanoemulsion. The
      prepared formulations were studied for globule size, zeta potential, refractive
      index, viscosity, surface morphology and in vitro and ex vivo release. The
      homogenized formulation, which contained 150 mg ml(-1) of resveratrol, showed
      spherical globules with an average globule diameter of 102 +/- 1.46 nm, a least
      poly dispersity index of 0.158 +/- 0.02 and optimal zeta potential values of -35
      +/- 0.02. The cumulative percentage drug release for the pre-homogenized
      resveratrol suspension, pre-homogenized nanoemulsion and post-homogenized
      nanoemulsion were 24.18 +/- 2.30%, 54.32 +/- 0.95% and 88.57 +/- 1.92%,
      respectively, after 24 h. The ex vivo release also showed the cumulative
      percentage drug release of 85.48 +/- 1.34% at 24 h. The antioxidant activity
      determined by using a DPPH assay showed high scavenging efficiency for the
      optimized formulation. Pharmacokinetic studies showed the higher concentration of
      the drug in the brain (brain/blood ratio: 2.86 +/- 0.70) following intranasal
      administration of the optimized nanoemulsion. Histopathological studies showed
      decreased degenerative changes in the resveratrol nanoemulsion administered
      groups. The levels of GSH and SOD were significantly higher, and the level of MDA
      was significantly lower in the resveratrol nanoemulsion treated group. 

PMID- 25392204
TI  - Characteristics of sexually experienced HIV testers aged 18 to 32 in rural South
      Africa: baseline results from a community-based trial, NIMH Project Accept (HPTN
      043).
AB  - BACKGROUND: Young people in South Africa are at high risk of HIV infection and
      yet may have more limited access to prevention and treatment services than others
      in the population. Testing facilitates the sharing of prevention messages but
      also enables the linkage to care and treatment of those who test positive and
      therefore has wider public health implications. METHODS: This baseline survey
      conducted in 2005 for a community randomized trial in rural KwaZulu-Natal
      explored factors associated with a history of ever, repeat and recent testing
      amongst sexually debuted men and women aged 18 to 32 years. RESULTS: Over 35% of
      this rural population ever tested for HIV, with men less likely to ever
      (unadjusted OR 0.26, 95% CI: 0.21-0.32) and repeatedly test than women (adjusted
      OR (aOR) 0.68, 95% CI: 0.48-0.97). Men aged 24-28 years (aOR 2.02, 95% CI: 1.10
      3.71) and 29-32 years (aOR 2.69, 95% CI: 1.46-4.94) were more likely to ever test
      than those <20 years. Those who reported having discussed HIV with others had
      significantly greater odds of reporting ever (men's aOR 2.83, 95% CI: 1.63-4.89;
      women's aOR 3.36, 95% CI: 2.50-4.53), recent (irrespective of sex, aOR 2.87, 95%
      CI: 2.02-4.09) and repeat testing (aOR 2.02, 95% CI: 1.28-3.19). CONCLUSION:
      These findings highlight the need for novel youth- and men-friendly testing
      services and emphasises the importance of discussions about HIV in the home and
      community to encourage testing.

PMID- 25392205
TI  - Effective bioconversion of sophoricoside to genistein from Fructus sophorae using
      immobilized Aspergillus niger and Yeast.
AB  - In this study, sophoricoside from Fructus sophorae was highly bioconversed to
      genistein by co-immobilized Aspergillus niger and Yeast. Bioconversion conditions
      for genistein were optimized with single-factor experiments. The optimal
      conditions were as follows: microbial concentration 1.5 * 10(7) cells/mL, wet
      weight of microorganisms beads 10.0 g/g material, pH 5, ratio of liquid to solid
      25:1 (mL/g), temperature 32  degrees C and time 24 h. Under these conditions, a
      34.45-fold increase in production of genistein was observed with a bioreactor.
      Moreover, the antioxidant activities of the extracts from the fermented and
      untreated F. sophorae were 0.287 +/- 0.11, 0.384 +/- 0.08 mg/mL (IC50) and 1.84
      +/- 0.13, 1.28 +/- 0.25 mmol Fe(II)/g, according to the DPPH test and FRAP assay,
      respectively. The results indicated that the method described in the current work
      were valuable procedure for the production of genistein, which is of most
      importance for industrial scale applications as well as food industry. 

PMID- 25392206
TI  - Three novel virophage genomes discovered from Yellowstone Lake metagenomes.
AB  - Virophages are a unique group of circular double-stranded DNA viruses that are
      considered parasites of giant DNA viruses, which in turn are known to infect
      eukaryotic hosts. In this study, the genomes of three novel Yellowstone Lake
      virophages (YSLVs)--YSLV5, YSLV6, and YSLV7--were identified from Yellowstone
      Lake through metagenomic analyses. The relative abundance of these three novel
      virophages and previously identified Yellowstone Lake virophages YSLV1 to -4 were
      determined in different locations of the lake, revealing that most of the sampled
      locations in the lake, including both mesophilic and thermophilic habitats, had
      multiple virophage genotypes. This likely reflects the diverse habitats or
      diversity of the eukaryotic hosts and their associated giant viruses that serve
      as putative hosts for these virophages. YSLV5 has a 29,767-bp genome with 32
      predicted open reading frames (ORFs), YSLV6 has a 24,837-bp genome with 29
      predicted ORFs, and YSLV7 has a 23,193-bp genome with 26 predicted ORFs. Based on
      multilocus phylogenetic analysis, YSLV6 shows a close evolutionary relationship
      with YSLV1 to -4, whereas YSLV5 and YSLV7 are distantly related to the others,
      and YSLV7 represents the fourth novel virophage lineage. In addition, the genome
      of YSLV5 has a G+C content of 51.1% that is much higher than all other known
      virophages, indicating a unique host range for YSLV5. These results suggest that
      virophages are abundant and have diverse genotypes that likely mirror diverse
      giant viral and eukaryotic hosts within the Yellowstone Lake ecosystem.
      IMPORTANCE: This study discovered novel virophages present within the Yellowstone
      Lake ecosystem using a conserved major capsid protein as a phylogenetic anchor
      for assembly of sequence reads from Yellowstone Lake metagenomic samples. The
      three novel virophage genomes (YSLV5 to -7) were completed by identifying
      specific environmental samples containing these respective virophages, and
      closing gaps by targeted PCR and sequencing. Most of the YSLV genotypes were
      associated primarily with photic-zone and nonhydrothermal samples; however, YSLV5
      had a unique distribution with an occurrence in vent samples similar to that in
      photic-zone samples and with a higher GC content that suggests a distinct host
      and habitat compared to other YSLVs. In addition, genome content and phylogenetic
      analyses indicate that YSLV5 and YSLV7 are distinct from known virophages and
      that additional as-yet-uncharacterized virophages are likely present within the
      Yellowstone Lake ecosystem.

PMID- 25392207
TI  - The nature of the N-terminal amino acid residue of HIV-1 RNase H is critical for
      the stability of reverse transcriptase in viral particles.
AB  - Reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is
      synthesized and packaged into the virion as a part of the GagPol polyprotein.
      Mature RT is released by the action of viral protease. However, unlike other
      viral proteins, RT is subject to an internal cleavage event leading to the
      formation of two subunits in the virion: a p66 subunit and a p51 subunit that
      lacks the RNase H domain. We have previously identified RNase H to be an HIV-1
      protein that has the potential to be a substrate for the N-end rule pathway,
      which is an ubiquitin-dependent proteolytic system in which the identity of the N
      terminal amino acid determines the half-life of a protein. Here we examined the
      importance of the N-terminal amino acid residue of RNase H in the early life
      cycle of HIV-1. We show that changing this residue to an amino acid structurally
      different from the conserved residue leads to the degradation of RT and, in some
      cases, integrase in the virus particle and this abolishes infectivity. Using
      intravirion complementation and in vitro protease cleavage assays, we show that
      degradation of RT in RNase H N-terminal mutants occurs in the absence of active
      viral protease in the virion. Our results also indicate the importance of the
      RNase H N-terminal residue in the dimerization of RT subunits. IMPORTANCE: HIV-1
      proteins are initially made as part of a polyprotein that is cleaved by the viral
      protease into the proteins that form the virus particle. We were interested in
      one particular protein, RNase H, that is cleaved from reverse transcriptase. In
      particular, we found that the first amino acid of RNase H never varied in over
      1,850 isolates of HIV-1 that we compared. When we changed the first amino acid,
      we found that the reverse transcriptase in the virus was degraded. While other
      studies have implied that the viral protease can degrade mutant RT proteins, we
      show here that this may not be the case for our mutants. Our results suggest that
      the presence of active viral protease is not required for the degradation of RT
      in RNase H N-terminal mutants, suggesting a role for a cellular protease in this
      process.

PMID- 25392208
TI  - Measles virus glycoprotein complexes preassemble intracellularly and relax during
      transport to the cell surface in preparation for fusion.
AB  - Measles virus (MeV), a morbillivirus within the paramyxovirus family, expresses
      two envelope glycoproteins. The attachment (H) protein mediates receptor binding,
      followed by triggering of the fusion (F) protein, which leads to merger of the
      viral envelope with target cell membranes. Receptor binding by members of related
      paramyxovirus genera rearranges the head domains of the attachment proteins,
      liberating an F-contact domain within the attachment protein helical stalk.
      However, morbillivirus glycoproteins first assemble intracellularly prior to
      receptor binding, raising the question of whether alternative protein-protein
      interfaces are involved or whether an entirely distinct triggering principle is
      employed. To test these possibilities, we generated headless H stem mutants of
      progressively shorter length. Conformationally restricted H stems remained
      capable of intracellular assembly with a standard F protein and a soluble MeV F
      mutant. Proteolytic maturation of F, but not the altered biochemical conditions
      at the cell surface, reduces the strength of glycoprotein interaction, readying
      the complexes for triggering. F mutants stabilized in the prefusion conformation
      interact with H intracellularly and at the cell surface, while destabilized F
      mutants interact only intracellularly, prior to F maturation. These results
      showcase an MeV entry machinery that functionally varies conserved motifs of the
      proposed paramyxovirus infection pathway. Intracellular and plasma membrane
      resident MeV glycoprotein complexes employ the same protein-protein interface. F
      maturation prepares for complex separation after triggering, and the H head
      domains in prereceptor-bound conformation prevent premature stalk rearrangements
      and F activation. Intracellular preassembly affects MeV fusion profiles and may
      contribute to the high cell-to-cell fusion activity characteristic of the
      morbillivirus genus. IMPORTANCE: Paramyxoviruses of the morbillivirus genus, such
      as measles, are highly contagious, major human and animal pathogens. MeV envelope
      glycoproteins preassemble intracellularly into tightly associated hetero
      oligomers. To address whether preassembly reflects a unique measles virus entry
      strategy, we characterized the protein-protein interface of intracellular and
      surface-exposed fusion complexes and investigated the effect of the attachment
      protein head domains, glycoprotein maturation, and altered biochemical conditions
      at the cell surface on measles virus fusion complexes. Our results demonstrate
      that measles virus functionally varies conserved elements of the paramyxovirus
      entry pathway, providing a possible explanation for the high cell-to-cell fusion
      activity of morbilliviruses. Insight gained from these data affects the design of
      effective broad-spectrum paramyxovirus entry inhibitors.

PMID- 25392209
TI  - The murine norovirus core subgenomic RNA promoter consists of a stable stem-loop
      that can direct accurate initiation of RNA synthesis.
AB  - All members of the Caliciviridae family of viruses produce a subgenomic RNA
      during infection. The subgenomic RNA typically encodes only the major and minor
      capsid proteins, but in murine norovirus (MNV), the subgenomic RNA also encodes
      the VF1 protein, which functions to suppress host innate immune responses. To
      date, the mechanism of norovirus subgenomic RNA synthesis has not been
      characterized. We have previously described the presence of an evolutionarily
      conserved RNA stem-loop structure on the negative-sense RNA, the complementary
      sequence of which codes for the viral RNA-dependent RNA polymerase (NS7). The
      conserved stem-loop is positioned 6 nucleotides 3' of the start site of the
      subgenomic RNA in all caliciviruses. We demonstrate that the conserved stem-loop
      is essential for MNV viability. Mutant MNV RNAs with substitutions in the stem
      loop replicated poorly until they accumulated mutations that revert to restore
      the stem-loop sequence and/or structure. The stem-loop sequence functions in a
      noncoding context, as it was possible to restore the replication of an MNV mutant
      by introducing an additional copy of the stem-loop between the NS7- and VP1
      coding regions. Finally, in vitro biochemical data suggest that the stem-loop
      sequence is sufficient for the initiation of viral RNA synthesis by the
      recombinant MNV RNA-dependent RNA polymerase, confirming that the stem-loop forms
      the core of the norovirus subgenomic promoter. IMPORTANCE: Noroviruses are a
      significant cause of viral gastroenteritis, and it is important to understand the
      mechanism of norovirus RNA synthesis. Here we describe the identification of an
      RNA stem-loop structure that functions as the core of the norovirus subgenomic
      RNA promoter in cells and in vitro. This work provides new insights into the
      molecular mechanisms of norovirus RNA synthesis and the sequences that determine
      the recognition of viral RNA by the RNA-dependent RNA polymerase.

PMID- 25392210
TI  - Specificity of coxsackievirus B3 interaction with human, but not murine, decay
      accelerating factor: replacement of a single residue within short consensus
      repeat 2 prevents virus attachment.
AB  - Many coxsackievirus B (CVB) isolates bind to human decay-accelerating factor
      (DAF) as well as to the coxsackievirus and adenovirus receptor (CAR). However,
      the virus does not interact with murine DAF. To understand why CVB3 binds
      specifically to human DAF, we constructed a series of chimeric molecules in which
      specific regions of the human DAF molecule were replaced by the corresponding
      murine sequences. We found that replacement of human short consensus repeat 2
      (SCR2) with murine SCR2 ablated virus binding to human DAF, as did deletion of
      human SCR2. Although replacement of human SCR4 had a partial inhibitory effect,
      deletion of SCR4 had no effect. Within human SCR2, replacement of serine 104
      (S104) with the proline residue found in murine DAF eliminated virus binding. On
      the basis of the structure of the CVB3-DAF complex determined by cryo-electron
      microscopy, DAF S104 is in close contact with a viral capsid residue, a threonine
      at VP1 position 271. Replacement of this capsid residue with larger amino acids
      specifically eliminated virus attachment to human DAF but had no effect on
      attachment to CAR or replication in HeLa cells. Taken together, these results
      support the current model of virus-DAF interaction and point to a specific role
      for VP1 T271 and DAF S104 at the virus-DAF interface. IMPORTANCE: The results of
      the present study point to a specific role for VP1 T271 and DAF S104 at the
      interface between CVB3 and DAF, and they demonstrate how subtle structural
      changes can dramatically influence virus-receptor interactions. In addition, the
      results support a recent pseudoatomic model of the CVB3-DAF interaction obtained
      by cryo-electron microscopy.

PMID- 25392211
TI  - Two distinct sets of NS2A molecules are responsible for dengue virus RNA
      synthesis and virion assembly.
AB  - Flavivirus nonstructural protein 2A (NS2A) plays important roles in both viral
      RNA synthesis and virion assembly. The molecular details of how the NS2A protein
      modulates the two distinct events have not been defined. To address this
      question, we have performed a systematic mutagenesis of NS2A using dengue virus
      (DENV) serotype 2 (DENV-2) as a model. We identified two sets of NS2A mutations
      with distinct defects during a viral infection cycle. One set of NS2A mutations
      (D125A and G200A) selectively abolished viral RNA synthesis. Mechanistically, the
      D125A mutation abolished viral RNA synthesis through blocking the N-terminal
      cleavage of the NS2A protein, leading to an unprocessed NS1-NS2A protein; this
      result suggests that amino acid D125 (far downstream of the N terminus of NS2A)
      may contribute to the recognition of host protease at the NS1-NS2A junction. The
      other set of NS2A mutations (G11A, E20A, E100A, Q187A, and K188A) specifically
      impaired virion assembly without significantly affecting viral RNA synthesis.
      Remarkably, mutants defective in virion assembly could be rescued by supplying in
      trans wild-type NS2A molecules expressed from a replicative replicon, by wild
      type NS2A protein expressed alone, by a mutant NS2A (G200A) that is lethal for
      viral RNA synthesis, or by a different mutant NS2A that is defective in virion
      assembly. In contrast, none of the mutants defective in viral RNA synthesis could
      be rescued by trans-complementation. Collectively, the results indicate that two
      distinct sets of NS2A molecules are responsible for DENV RNA synthesis and virion
      assembly. IMPORTANCE: Dengue virus (DENV) represents the most prevalent mosquito
      borne human pathogen. Understanding the replication of DENV is essential for
      development of vaccines and therapeutics. Here we characterized the function of
      DENV-2 NS2A using a systematic mutagenesis approach. The mutagenesis results
      revealed two distinct sets of NS2A mutations: one set of mutations that result in
      defects in viral RNA synthesis and another set of mutations that result in
      defects in virion assembly. trans-Complementation analysis showed that mutants
      defective in viral RNA synthesis could not be rescued by wild-type NS2A; in
      contrast, mutants defective in virion assembly could be successfully rescued by
      wild-type NS2A or even by a mutant NS2A that is incompetent to support viral RNA
      synthesis. These results support a model in which two distinct sets of NS2A
      molecules are responsible for DENV RNA synthesis (located in the viral
      replication complex) and virion assembly (located in the virion assembly/budding
      site). The study confirms and extends our understanding of the two critical roles
      of flavivirus NS2A in viral RNA synthesis and virion assembly.

PMID- 25392212
TI  - Less is more: Ebola virus surface glycoprotein expression levels regulate virus
      production and infectivity.
AB  - The Ebola virus (EBOV) surface glycoprotein (GP1,2) mediates host cell attachment
      and fusion and is the primary target for host neutralizing antibodies. Expression
      of GP1,2 at high levels disrupts normal cell physiology, and EBOV uses an RNA
      editing mechanism to regulate expression of the GP gene. In this study, we
      demonstrate that high levels of GP1,2 expression impair production and release of
      EBOV virus-like particles (VLPs) as well as infectivity of GP1,2-pseudotyped
      viruses. We further show that this effect is mediated through two mechanisms.
      First, high levels of GP1,2 expression reduce synthesis of other proteins needed
      for virus assembly. Second, viruses containing high levels of GP1,2 are
      intrinsically less infectious, possibly due to impaired receptor binding or
      endosomal processing. Importantly, proteolysis can rescue the infectivity of high
      GP1,2-containing viruses. Taken together, our findings indicate that GP1,2
      expression levels have a profound effect on factors that contribute to virus
      fitness and that RNA editing may be an important mechanism employed by EBOV to
      regulate GP1,2 expression in order to optimize virus production and infectivity.
      IMPORTANCE: The Ebola virus (EBOV), as well as other members of the Filoviridae
      family, causes severe hemorrhagic fever that is highly lethal, with up to 90%
      mortality. The EBOV surface glycoprotein (GP1,2) plays important roles in virus
      infection and pathogenesis, and its expression is tightly regulated by an RNA
      editing mechanism during virus replication. Our study demonstrates that the level
      of GP1,2 expression profoundly affects virus particle production and release and
      uncovers a new mechanism by which Ebola virus infectivity is regulated by the
      level of GP1,2 expression. These findings extend our understanding of EBOV
      infection and replication in adaptation of host environments, which will aid the
      development of countermeasures against EBOV infection.

PMID- 25392213
TI  - Abrogation of the interferon response promotes more efficient human
      cytomegalovirus replication.
AB  - The effect of abrogating the interferon (IFN) response on human cytomegalovirus
      (HCMV) replication was investigated using primary human cells engineered to block
      either the production of or the response to type I IFNs. In IFN-deficient cells,
      HCMV produced larger plaques and spread and replicated more rapidly than in
      parental cells. These cells demonstrate the vital role of IFNs in controlling
      HCMV replication and provide useful tools to investigate the IFN response to
      HCMV. 

PMID- 25392214
TI  - JC virus quasispecies analysis reveals a complex viral population underlying
      progressive multifocal leukoencephalopathy and supports viral dissemination via
      the hematogenous route.
AB  - Opportunistic infection of oligodendrocytes by human JC polyomavirus may result
      in the development of progressive multifocal encephalopathy in immunocompromised
      individuals. Neurotropic JC virus generally harbors reorganized noncoding control
      region (NCCR) DNA interspersed on the viral genome between early and late coding
      genes. By applying 454 sequencing on NCCR DNA amplified from body fluid samples
      (urine, plasma, and cerebrospinal fluid [CSF]) from 19 progressive multifocal
      leukoencephalopathy (PML) patients, we attempted to reveal the composition of the
      JC polyomavirus population (the quasispecies, i.e., the whole of the consensus
      population and minor viral variants) contained in different body compartments and
      to better understand intrapatient viral dissemination. Our data demonstrate that
      in the CSF of PML patients, the JC viral population is often a complex mixture
      composed of multiple viral variants that contribute to the quasispecies. In
      contrast, urinary JC virus highly resembled the archetype virus, and urine most
      often did not contain minor viral variants. It also appeared that archetype JC
      virus could sporadically be identified in PML patient brain, although selection
      of rearranged JC virus DNA was favored. Comparison of the quasispecies from
      different body compartments within a given patient suggested a strong correlation
      between the viral population in plasma and CSF, whereas the viral population shed
      in urine appeared to be unrelated. In conclusion, it is shown that the
      representation of viral DNA in the CSF following the high-level DNA replication
      in the brain underlying PML has hitherto been much underestimated. Our data also
      underscore that the hematogenous route might play a pivotal role in viral
      dissemination from or toward the brain. IMPORTANCE: For the first time, the JC
      polyomavirus population contained in different body compartments of patients
      diagnosed with progressive multifocal encephalopathy has been studied by deep
      sequencing. Two main findings came out of this work. First, it became apparent
      that the complexity of the viral population associated with PML has been highly
      underestimated so far, suggestive of a highly dynamic process of reorganization
      of the noncoding control region of JC polyomavirus in vivo, mainly in CSF and
      blood. Second, evidence showing viral dissemination from and/or toward the brain
      via the hematogenous route was provided, confirming a hypothesis that was
      recently put forward in the field.

PMID- 25392215
TI  - Distinct characteristics of endometrial and decidual macrophages and regulation
      of their permissivity to HIV-1 infection by SAMHD1.
AB  - In order to develop strategies to prevent HIV-1 (human immunodeficiency virus
      type 1) transmission, it is crucial to better characterize HIV-1 target cells in
      the female reproductive tract (FRT) mucosae and to identify effective innate
      responses. Control of HIV-1 infection in the decidua (the uterine mucosa during
      pregnancy) can serve as a model to study natural mucosal protection. Macrophages
      are the main HIV-1 target cells in the decidua. Here we report that in vitro,
      macrophages and T cells are the main HIV-1 targets in the endometrium in
      nonpregnant women. As reported for decidual macrophages (dM), endometrial
      macrophages (eM) were found to have an M2-like phenotype (CD68+ CD163+ CD206+ IL
      10high). However, eM and dM may belong to different subpopulations, as they
      differently express certain markers and secrete different amounts of
      proinflammatory and anti-inflammatory cytokines. We observed strong expression of
      the SAMHD1 restriction factor and weak expression of its inactive form (pSAMHD1,
      phosphorylated at residue Thr592) in both eM and dM. Infection of macrophages
      from both tissues was enhanced in the presence of the viral protein Vpx,
      suggesting a role for SAMHD1 in the restriction of HIV-1 infection. This study
      and further comparisons of the decidua with FRT mucosae in nonpregnant women
      should help to identify mechanisms of mucosal protection against HIV-1 infection.
      IMPORTANCE: The female reproductive tract mucosae are major portals of HIV-1
      entry into the body. The decidua (uterine mucosa during pregnancy) can serve as a
      model for studying natural mucosal protection against HIV-1 transmission. A
      comparison of target cells and innate responses in the decidua versus the
      endometrium in nonpregnant women could help to identify protective mechanisms.
      Here, we report for the first time that macrophages are one of the main HIV-1
      target cells in the endometrium and that infection of macrophages from both the
      endometrium and the decidua is restricted by SAMHD1. These findings might have
      implications for the development of vaccines to prevent HIV-1 mucosal
      transmission.

PMID- 25392216
TI  - Structure-based functional analyses of domains II and III of pseudorabies virus
      glycoprotein H.
AB  - Enveloped viruses utilize membrane fusion for entry into, and release from, host
      cells. For entry, members of the Herpesviridae require at least three envelope
      glycoproteins: the homotrimeric gB and a heterodimer of gH and gL. The crystal
      structures of three gH homologues, including pseudorabies virus (PrV) gH,
      revealed four conserved domains. Domain II contains a planar beta-sheet ("fence")
      and a syntaxin-like bundle of three alpha-helices (SLB), similar to those found
      in eukaryotic fusion proteins, potentially executing an important role in gH
      function. To test this hypothesis, we introduced targeted mutations into the PrV
      gH gene, which either disrupt the helices of the SLB by introduction of proline
      residues or covalently join them by artificial intramolecular disulfide bonds
      between themselves, to the adjacent fence region, or to domain III. Disruption of
      either of the three alpha-helices of the SLB (A250P, V275P, V298P) severely
      affected gH function in in vitro fusion assays and replication of corresponding
      PrV mutants. Considerable defects in fusion activity of gH, as well as in
      penetration kinetics and cell-to-cell spread of PrV mutants, were also observed
      after disulfide linkage of two alpha-helices within the SLB (A284C-S291C) or
      between SLB and domain III (H251C-L432C), as well as by insertions of additional
      cysteine pairs linking fence, SLB, and domain III. In vitro fusion activity of
      mutated gH could be partly restored by reduction of the artificial disulfide
      bonds. Our results indicate that the structure and flexibility of the SLB are
      relevant for the function of PrV gH in membrane fusion. IMPORTANCE: Mutational
      analysis based on crystal structures of proteins is a powerful tool to understand
      protein function. Here, we continued our study of pseudorabies virus gH, a part
      of the core fusion machinery of herpesviruses. We previously showed that the
      "flap" region in domain IV of PrV gH is important for its function. We now
      demonstrate that mutations within domain II that interfere with integrity or
      flexibility of a syntaxin-like three-helix bundle also significantly impair gH
      function during fusion. These studies provide important insights into the
      structural requirements of gH for function in fusion.

PMID- 25392217
TI  - A lethal murine infection model for dengue virus 3 in AG129 mice deficient in
      type I and II interferon receptors leads to systemic disease.
AB  - The mosquito-borne disease dengue (DEN) is caused by four serologically and
      genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV
      usually leads to acute illness and results in lifelong homotypic immunity, but
      individuals remain susceptible to infection by the other three DENVs. The lack of
      a small-animal model that mimics systemic DEN disease without neurovirulence has
      been an obstacle, but DENV-2 models that resemble human disease have been
      recently developed in AG129 mice (deficient in interferon alpha/beta and
      interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4
      models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human
      isolate to develop a lethal infection model in AG129 mice. Intraperitoneal
      inoculation of six to eight-week-old animals with strain C0360/94 led to rapid,
      fatal disease. Lethal C0360/94 infection resulted in physical signs of illness,
      high viral loads in the spleen, liver, and large intestine, histological changes
      in the liver and spleen tissues, and increased serum cytokine levels.
      Importantly, the animals developed vascular leakage, thrombocytopenia, and
      leukopenia. Overall, we have developed a lethal DENV-3 murine infection model,
      with no evidence of neurotropic disease based on a non-mouse-adapted human
      isolate, which can be used to investigate DEN pathogenesis and to evaluate
      candidate vaccines and antivirals. This suggests that murine models utilizing non
      mouse-adapted isolates can be obtained for all four DENVs. IMPORTANCE: Dengue
      (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3,
      and -4) that have no treatments or vaccines. Primary infection with one DENV
      usually leads to acute illness followed by lifelong homotypic immunity, but
      susceptibility to infection by the other three DENVs remains. Therefore, a
      vaccine needs to protect from all four DENVs simultaneously. To date a suitable
      animal model to mimic systemic human illness exists only for DENV-2 in
      immunocompromised mice using passaged viruses; however, models are still needed
      for the remaining serotypes. This study describes establishment of a lethal
      systemic DENV-3 infection model with a human isolate in immunocompromised mice
      and is the first report of lethal infection by a nonadapted clinical DENV isolate
      without evidence of neurological disease. Our DENV-3 model provides a relevant
      platform to test DEN vaccines and antivirals.

PMID- 25392218
TI  - Efficient reverse genetics reveals genetic determinants of budding and fusogenic
      differences between Nipah and Hendra viruses and enables real-time monitoring of
      viral spread in small animal models of henipavirus infection.
AB  - Nipah virus (NiV) and Hendra virus (HeV) are closely related henipaviruses of the
      Paramyxovirinae. Spillover from their fruit bat reservoirs can cause severe
      disease in humans and livestock. Despite their high sequence similarity, NiV and
      HeV exhibit apparent differences in receptor and tissue tropism, envelope
      mediated fusogenicity, replicative fitness, and other pathophysiologic
      manifestations. To investigate the molecular basis for these differences, we
      first established a highly efficient reverse genetics system that increased
      rescue titers by >=3 log units, which offset the difficulty of generating
      multiple recombinants under constraining biosafety level 4 (BSL-4) conditions. We
      then replaced, singly and in combination, the matrix (M), fusion (F), and
      attachment glycoprotein (G) genes in mCherry-expressing recombinant NiV (rNiV)
      with their HeV counterparts. These chimeric but isogenic rNiVs replicated well in
      primary human endothelial and neuronal cells, indicating efficient heterotypic
      complementation. The determinants of budding efficiency, fusogenicity, and
      replicative fitness were dissociable: HeV-M budded more efficiently than NiV-M,
      accounting for the higher replicative titers of HeV-M-bearing chimeras at early
      times, while the enhanced fusogenicity of NiV-G-bearing chimeras did not
      correlate with increased replicative fitness. Furthermore, to facilitate
      spatiotemporal studies on henipavirus pathogenesis, we generated a firefly
      luciferase-expressing NiV and monitored virus replication and spread in infected
      interferon alpha/beta receptor knockout mice via bioluminescence imaging. While
      intraperitoneal inoculation resulted in neuroinvasion following systemic spread
      and replication in the respiratory tract, intranasal inoculation resulted in
      confined spread to regions corresponding to olfactory bulbs and salivary glands
      before subsequent neuroinvasion. This optimized henipavirus reverse genetics
      system will facilitate future investigations into the growing numbers of novel
      henipavirus-like viruses. IMPORTANCE: Nipah virus (NiV) and Hendra virus (HeV)
      are recently emergent zoonotic and highly lethal pathogens with pandemic
      potential. Although differences have been observed between NiV and HeV
      replication and pathogenesis, the molecular basis for these differences has not
      been examined. In this study, we established a highly efficient system to reverse
      engineer changes into replication-competent NiV and HeV, which facilitated the
      generation of reporter-expressing viruses and recombinant NiV-HeV chimeras with
      substitutions in the genes responsible for viral exit (the M gene, critical for
      assembly and budding) and viral entry (the G [attachment] and F [fusion] genes).
      These chimeras revealed differences in the budding and fusogenic properties of
      the M and G proteins, respectively, which help explain previously observed
      differences between NiV and HeV. Finally, to facilitate future in vivo studies,
      we monitored the replication and spread of a bioluminescent reporter-expressing
      NiV in susceptible mice; this is the first time such in vivo imaging has been
      performed under BSL-4 conditions.

PMID- 25392219
TI  - Electron cryotomography studies of maturing HIV-1 particles reveal the assembly
      pathway of the viral core.
AB  - To better characterize the assembly of the HIV-1 core, we have used electron
      cryotomography (ECT) to image infected cells and the viral particles
      cryopreserved next to them. We observed progressive stages of virus assembly and
      egress, including flower-like flat Gag lattice assemblies, hemispherical budding
      profiles, and virus buds linked to the plasma membrane via a thin membrane neck.
      The population of budded viral particles contains immature, maturation
      intermediate, and mature core morphologies. Structural characteristics of the
      maturation intermediates suggest that the core assembly pathway involves the
      formation of a CA sheet that associates with the condensed ribonucleoprotein
      (RNP) complex. Our analysis also reveals a correlation between RNP localization
      within the viral particle and the formation of conical cores, suggesting that the
      RNP helps drive conical core assembly. Our findings support an assembly pathway
      for the HIV-1 core that begins with a small CA sheet that associates with the RNP
      to form the core base, followed by polymerization of the CA sheet along one side
      of the conical core toward the tip, and then closure around the body of the cone.
      IMPORTANCE: During HIV-1 assembly and release, the Gag polyprotein is organized
      into a signature hexagonal lattice, termed the immature lattice. To become
      infectious, the newly budded virus must disassemble the immature lattice by
      proteolyzing Gag and then reassemble the key proteolytic product, the structural
      protein p24 (CA), into a distinct, mature hexagonal lattice during a process
      termed maturation. The mature HIV-1 virus contains a conical capsid that encloses
      the condensed viral genome at its wide base. Mutations or small molecules that
      interfere with viral maturation also disrupt viral infectivity. Little is known
      about the assembly pathway that results in the conical core and genome
      encapsidation. Here, we have used electron cryotomography to structurally
      characterize HIV-1 particles that are actively maturing. Based on the
      morphologies of core assembly intermediates, we propose that CA forms a sheet
      like structure that associates with the condensed viral genome to produce the
      mature infectious conical core.

PMID- 25392220
TI  - The ORF012 gene of Marek's disease virus type 1 produces a spliced transcript and
      encodes a novel nuclear phosphoprotein essential for virus growth.
AB  - Marek's disease virus (MDV), an alphaherpesvirus, is the causative agent of a
      lethal disease in chickens characterized by generalized nerve inflammation and
      rapid lymphoma development. The extensive colinearity of the MDV genome with
      those of related herpesviruses has eased functional characterization of many MDV
      genes. However, MDV carries a number of unique open reading frames (ORFs) that
      have not yet been investigated regarding their coding potentials and the
      functions of their products. Among these unique ORFs are two putative ORFs,
      ORF011 and ORF012, which are found at the extreme left end of the MDV unique long
      region. Using reverse transcriptase PCR, we showed that ORF011 and ORF012 are not
      individual genes but form a single gene through mRNA splicing of a small intron,
      resulting in the novel ORF012. We generated an ORF012-null virus using an
      infectious clone of MDV strain RB-1B. The deletion virus had a marked growth
      defect in vitro and could not be passaged in cultured cells, suggesting an
      essential role for the ORF012 product in virus replication. Further studies
      revealed that protein 012 (p012) localized to the nucleus in transfected and
      infected cells, and we identified by site-directed mutagenesis and green
      fluorescent protein (GFP) reporter fusion assays a nuclear localization signal
      (NLS) that was mapped to a 23-amino-acid sequence at the protein's C terminus.
      Nuclear export was blocked using leptomycin B, suggesting a potential role for
      p012 as a nuclear/cytoplasmic shuttling protein. Finally, p012 is phosphorylated
      at multiple residues, a modification that could possibly regulate its subcellular
      distribution. IMPORTANCE: Marek's disease virus (MDV) causes a devastating
      oncogenic disease in chickens with high morbidity and mortality. The costs for
      disease prevention reach several billion dollars annually. The functional
      investigation of MDV genes is necessary to understand its complex replication
      cycle, which eventually could help us to interfere with MDV and herpesviral
      pathogenesis. We have identified a previously unidentified phosphoprotein encoded
      by MDV ORF012. We were able to show experimentally that predicted splicing of the
      gene based on bioinformatics data does indeed occur during replication. The newly
      identified p012 is essential for MDV replication and localizes to the nucleus due
      to the presence of a transferable nuclear localization signal at its C terminus.
      Our results also imply that p012 could constitute a nucleocytoplasmic shuttle
      protein, a feature that could prove interesting and important.

PMID- 25392221
TI  - Ebola virus transmission in guinea pigs.
AB  - Ebola virus (EBOV) transmission is currently poorly characterized and is thought
      to occur primarily by direct contact with infectious material; however
      transmission from swine to nonhuman primates via the respiratory tract has been
      documented. To establish an EBOV transmission model for performing studies with
      statistical significance, groups of six guinea pigs (gps) were challenged
      intranasally (i.n.) or intraperitoneally (i.p.) with 10,000 times the 50% lethal
      dose (LD50) of gp-adapted EBOV, and naive gps were then introduced as cage mates
      for contact exposure at 1 day postinfection (p.i.). The animals were monitored
      for survival and clinical signs of disease and quantitated for virus shedding
      postexposure. Changes in the duration of contact of naive gps with infected
      animals were evaluated for their impact on transmission efficiency. Transmission
      was more efficient from i.n.- than from i.p.-challenged gps, with 17% versus 83%
      of naive gps surviving exposure, respectively. Virus shedding was detected
      beginning at 3 days p.i. from both i.n.- and i.p.-challenged animals. Contact
      duration positively correlated with transmission efficiency, and the abrogation
      of direct contact between infected and naive animals through the erection of a
      steel mesh was effective at stopping virus spread, provided that infectious
      animal bedding was absent from the cages. Histopathological and
      immunohistochemical findings show that i.n.-infected gps display enhanced lung
      pathology and EBOV antigen in the trachea, which supports increased virus
      transmission from these animals. The results suggest that i.n.-challenged gps are
      more infectious to naive animals than their systemically infected counterparts
      and that transmission occurs through direct contact with infectious materials,
      including those transported through air movement over short distances.
      IMPORTANCE: Ebola is generally thought to be spread between humans though
      infectious bodily fluids. However, a study has shown that Ebola can be spread
      from pigs to monkeys without direct contact. Further studies have been hampered,
      because an economical animal model for Ebola transmission is not available. To
      address this, we established a transmission model in guinea pigs and determined
      the mechanisms behind virus spread. The survival data, in addition to microscopic
      examination of lung and trachea sections, show that mucosal infection of guinea
      pigs is an efficient model for Ebola transmission. Virus spread is increased with
      longer contact times with an infected animal and is possible without direct
      contact between an infected and a naive host but can be stopped if infectious
      materials are absent. These results warrant consideration for the development of
      future strategies against Ebola transmission and for a better understanding of
      the parameters involved in virus spread.

PMID- 25392222
TI  - Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced
      ultrastructural changes and accumulation of protein in the endoplasmic reticulum.
AB  - We have previously shown that ablation of the three N-linked glycosylation sites
      in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness
      (>=1,000,000 PFU). Here, we compared the replication of the NS1130
      132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero
      cells. The results suggest that the mechanism of attenuation is a lack of NS1
      glycosylation, which blocks efficient replication, maturation, and NS1 secretion
      from the endoplasmic reticulum and results in changes to the virus-induced
      ultrastructure. 

PMID- 25392223
TI  - Cyclic avian mass mortality in the northeastern United States is associated with
      a novel orthomyxovirus.
AB  - Since 1998, cyclic mortality events in common eiders (Somateria mollissima),
      numbering in the hundreds to thousands of dead birds, have been documented along
      the coast of Cape Cod, MA, USA. Although longitudinal disease investigations have
      uncovered potential contributing factors responsible for these outbreaks,
      detecting a primary etiological agent has proven enigmatic. Here, we identify a
      novel orthomyxovirus, tentatively named Wellfleet Bay virus (WFBV), as a
      potential causative agent of these outbreaks. Genomic analysis of WFBV revealed
      that it is most closely related to members of the Quaranjavirus genus within the
      family Orthomyxoviridae. Similar to other members of the genus, WFBV contains an
      alphabaculovirus gp64-like glycoprotein that was demonstrated to have fusion
      activity; this also tentatively suggests that ticks (and/or insects) may vector
      the virus in nature. However, in addition to the six RNA segments encoding the
      prototypical structural proteins identified in other quaranjaviruses, a
      previously unknown RNA segment (segment 7) encoding a novel protein designated
      VP7 was discovered in WFBV. Although WFBV shows low to moderate levels of
      sequence similarity to Quaranfil virus and Johnston Atoll virus, the original
      members of the Quaranjavirus genus, additional antigenic and genetic analyses
      demonstrated that it is closely related to the recently identified Cygnet River
      virus (CyRV) from South Australia, suggesting that WFBV and CyRV may be
      geographic variants of the same virus. Although the identification of WFBV in
      part may resolve the enigma of these mass mortality events, the details of the
      ecology and epidemiology of the virus remain to be determined. IMPORTANCE: The
      emergence or reemergence of viral pathogens resulting in large-scale outbreaks of
      disease in humans and/or animals is one of the most important challenges facing
      biomedicine. For example, understanding how orthomyxoviruses such as novel
      influenza A virus reassortants and/or mutants emerge to cause epidemic or
      pandemic disease is at the forefront of current global health concerns. Here, we
      describe the emergence of a novel orthomyxovirus, Wellfleet Bay virus (WFBV),
      which has been associated with cyclic large-scale bird die-offs in the
      northeastern United States. This initial characterization study provides a
      foundation for further research into the evolution, epidemiology, and ecology of
      newly emerging orthomyxoviruses, such as WFBV, and their potential impacts on
      animal and/or human health.

PMID- 25392224
TI  - A cryo-electron microscopy study identifies the complete H16.V5 epitope and
      reveals global conformational changes initiated by binding of the neutralizing
      antibody fragment.
AB  - Human papillomavirus 16 (HPV16) is a worldwide health threat and an etiologic
      agent of cervical cancer. To understand the antigenic properties of HPV16, we
      pursued a structural study to elucidate HPV capsids and antibody interactions.
      The cryo-electron microscopy (cryo-EM) structures of a mature HPV16 particle and
      an altered capsid particle were solved individually and as complexes with
      fragment of antibody (Fab) from the neutralizing antibody H16.V5. Fitted crystal
      structures provided a pseudoatomic model of the virus-Fab complex, which
      identified a precise footprint of H16.V5, including previously unrecognized
      residues. The altered-capsid-Fab complex map showed that binding of the Fab
      induced significant conformational changes that were not seen in the altered
      capsid structure alone. These changes included more ordered surface loops,
      consolidated so-called "invading-arm" structures, and tighter intercapsomeric
      connections at the capsid floor. The H16.V5 Fab preferentially bound hexavalent
      capsomers likely with a stabilizing effect that directly correlated with the
      number of bound Fabs. Additional cryo-EM reconstructions of the virus-Fab complex
      for different incubation times and structural analysis provide a model for a
      hyperstabilization of the capsomer by H16.V5 Fab and showed that the Fab
      distinguishes subtle differences between antigenic sites. IMPORTANCE: Our
      analysis of the cryo-EM reconstructions of the HPV16 capsids and virus-Fab
      complexes has identified the entire HPV.V5 conformational epitope and
      demonstrated a detailed neutralization mechanism of this clinically important
      monoclonal antibody against HPV16. The Fab bound and ordered the apical loops of
      HPV16. This conformational change was transmitted to the lower region of the
      capsomer, resulting in enhanced intercapsomeric interactions evidenced by the
      more ordered capsid floor and "invading-arm" structures. This study advances the
      understanding of the neutralization mechanism used by H16.V5.

PMID- 25392225
TI  - Biological and protective properties of immune sera directed to the influenza
      virus neuraminidase.
AB  - The envelope of influenza A viruses contains two large antigens, hemagglutinin
      (HA) and neuraminidase (NA). Conventional influenza virus vaccines induce
      neutralizing antibodies that are predominantly directed to the HA globular head,
      a domain that is subject to extensive antigenic drift. Antibodies directed to NA
      are induced at much lower levels, probably as a consequence of the
      immunodominance of the HA antigen. Although antibodies to NA may affect virus
      release by inhibiting the sialidase function of the glycoprotein, the antigen has
      been largely neglected in past vaccine design. In this study, we characterized
      the protective properties of monospecific immune sera that were generated by
      vaccination with recombinant RNA replicon particles encoding NA. These immune
      sera inhibited hemagglutination in an NA subtype-specific and HA subtype
      independent manner and interfered with infection of MDCK cells. In addition, they
      inhibited the sialidase activities of various influenza viruses of the same and
      even different NA subtypes. With this, the anti-NA immune sera inhibited the
      spread of H5N1 highly pathogenic avian influenza virus and HA/NA-pseudotyped
      viruses in MDCK cells in a concentration-dependent manner. When chickens were
      immunized with NA recombinant replicon particles and subsequently infected with
      low-pathogenic avian influenza virus, inflammatory serum markers were
      significantly reduced and virus shedding was limited or eliminated. These
      findings suggest that NA antibodies can inhibit virus dissemination by
      interfering with both virus attachment and egress. Our results underline the
      potential of high-quality NA antibodies for controlling influenza virus
      replication and place emphasis on NA as a vaccine antigen. IMPORTANCE: The
      neuraminidase of influenza A viruses is a sialidase that acts as a receptor
      destroying enzyme facilitating the release of progeny virus from infected cells.
      Here, we demonstrate that monospecific anti-NA immune sera inhibited not only
      sialidase activity, but also influenza virus hemagglutination and infection of
      MDCK cells, suggesting that NA antibodies can interfere with virus attachment.
      Inhibition of both processes, virus release and virus binding, may explain why NA
      antibodies efficiently blocked virus dissemination in vitro and in vivo. Anti-NA
      immune sera showed broader reactivity than anti-HA sera in hemagglutination
      inhibition tests and demonstrated cross-subtype activity in sialidase inhibition
      tests. These remarkable features of NA antibodies highlight the importance of the
      NA antigen for the development of next-generation influenza virus vaccines.

PMID- 25392226
TI  - Tulane virus recognizes the A type 3 and B histo-blood group antigens.
AB  - Tulane virus (TV), the prototype of the Recovirus genus in the calicivirus
      family, was isolated from the stools of rhesus monkeys and can be cultivated in
      vitro in monkey kidney cells. TV is genetically closely related to the genus
      Norovirus and recognizes the histo-blood group antigens (HBGAs), similarly to
      human noroviruses (NoVs), making it a valuable surrogate for human NoVs. However,
      the precise structures of HBGAs recognized by TV remain elusive. In this study,
      we performed binding and blocking experiments on TV with extended HBGA types and
      showed that, while TV binds all four types (types 1 to 4) of the B antigens, it
      recognizes only the A type 3 antigen among four types of A antigens tested. The
      requirements for HBGAs in TV replication were demonstrated by blocking of TV
      replication in cell culture using the A type 3/4 and B saliva samples. Similar
      results were also observed in oligosaccharide-based blocking assays. Importantly,
      the previously reported, unexplained increase in TV replication by
      oligosaccharide in cell-based blocking assays has been clarified, which will
      facilitate the application of TV as a surrogate for human NoVs. IMPORTANCE: Our
      understanding of the role of HBGAs in NoV infection has been significantly
      advanced in the past decade, but direct evidence for HBGAs as receptors for human
      NoVs remains lacking due to a lack of a cell culture method. TV recognizes HBGAs
      and can replicate in vitro, providing a valuable surrogate for human NoVs.
      However, TV binds to some but not all saliva samples from A-positive individuals,
      and an unexplained observation of synthetic oligosaccharide blocking of TV
      binding has been reported. These issues have been resolved in this study.

PMID- 25392227
TI  - Eilat virus host range restriction is present at multiple levels of the virus
      life cycle.
AB  - Most alphaviruses are mosquito-borne and exhibit a broad host range, infecting
      many different vertebrates, including birds, rodents, equids, humans, and
      nonhuman primates. This ability of most alphaviruses to infect arthropods and
      vertebrates is essential for their maintenance in nature. Recently, a new
      alphavirus, Eilat virus (EILV), was described, and in contrast to all other
      mosquito-borne viruses, it is unable to replicate in vertebrate cell lines.
      Investigations into the nature of its host range restriction showed the inability
      of genomic EILV RNA to replicate in vertebrate cells. Here, we investigated
      whether the EILV host range restriction is present at the entry level and further
      explored the viral factors responsible for the lack of genomic RNA replication.
      Utilizing Sindbis virus (SINV) and EILV chimeras, we show that the EILV
      vertebrate host range restriction is also manifested at the entry level.
      Furthermore, the EILV RNA replication restriction is independent of the 3'
      untranslated genome region (UTR). Complementation experiments with SINV suggested
      that RNA replication is restricted by the inability of the EILV nonstructural
      proteins to form functional replicative complexes. These data demonstrate that
      the EILV host range restriction is multigenic, involving at least one gene from
      both nonstructural protein (nsP) and structural protein (sP) open reading frames
      (ORFs). As EILV groups phylogenetically within the mosquito-borne virus clade of
      pathogenic alphaviruses, our findings have important evolutionary implications
      for arboviruses. IMPORTANCE: Our work explores the nature of host range
      restriction of the first "mosquito-only alphavirus," EILV. EILV is related to
      pathogenic mosquito-borne viruses (Eastern equine encephalitis virus [EEEV],
      Western equine encephalitis virus [WEEV], Venezuelan equine encephalitis virus
      [VEEV], and Chikungunya virus [CHIKV]) that cause severe disease in humans. Our
      data demonstrate that EILV is restricted both at entry and genomic RNA
      replication levels in vertebrate cells. These findings have important
      implications for arbovirus evolution and will help elucidate the viral factors
      responsible for the broad host range of pathogenic mosquito-borne alphaviruses,
      facilitate vaccine development, and inform potential strategies to reduce/prevent
      alphavirus transmission.

PMID- 25392228
TI  - Wongabel rhabdovirus accessory protein U3 targets the SWI/SNF chromatin
      remodeling complex.
AB  - Wongabel virus (WONV) is an arthropod-borne rhabdovirus that infects birds. It is
      one of the growing array of rhabdoviruses with complex genomes that encode
      multiple accessory proteins of unknown function. In addition to the five
      canonical rhabdovirus structural protein genes (N, P, M, G, and L), the 13.2-kb
      negative-sense single-stranded RNA (ssRNA) WONV genome contains five
      uncharacterized accessory genes, one overlapping the N gene (Nx or U4), three
      located between the P and M genes (U1 to U3), and a fifth one overlapping the G
      gene (Gx or U5). Here we show that WONV U3 is expressed during infection in
      insect and mammalian cells and is required for efficient viral replication. A
      yeast two-hybrid screen against a mosquito cell cDNA library identified that WONV
      U3 interacts with the 83-amino-acid (aa) C-terminal domain of SNF5, a component
      of the SWI/SNF chromatin remodeling complex. The interaction was confirmed by
      affinity chromatography, and nuclear colocalization was established by confocal
      microscopy. Gene expression studies showed that SNF5 transcripts are upregulated
      during infection of mosquito cells with WONV, as well as West Nile virus
      (Flaviviridae) and bovine ephemeral fever virus (Rhabdoviridae), and that SNF5
      knockdown results in increased WONV replication. WONV U3 also inhibits SNF5
      regulated expression of the cytokine gene CSF1. The data suggest that WONV U3
      targets the SWI/SNF complex to block the host response to infection. IMPORTANCE:
      The rhabdoviruses comprise a large family of RNA viruses infecting plants,
      vertebrates, and invertebrates. In addition to the major structural proteins (N,
      P, M, G, and L), many rhabdoviruses encode a diverse array of accessory proteins
      of largely unknown function. Understanding the role of these proteins may reveal
      much about host-pathogen interactions in infected cells. Here we examine
      accessory protein U3 of Wongabel virus, an arthropod-borne rhabdovirus that
      infects birds. We show that U3 enters the nucleus and interacts with SNF5, a
      component of the chromatin remodeling complex that is upregulated in response to
      infection and restricts viral replication. We also show that U3 inhibits SNF5
      regulated expression of the cytokine colony-stimulating factor 1 (CSF1),
      suggesting that it targets the chromatin remodeling complex to block the host
      response to infection. This study appears to provide the first evidence of a
      virus targeting SNF5 to inhibit host gene expression.

PMID- 25392229
TI  - Phospho-NSAIDs have enhanced efficacy in mice lacking plasma carboxylesterase:
      implications for their clinical pharmacology.
AB  - PURPOSE: The purpose of the study was to evaluate the metabolism,
      pharmacokinetics and efficacy of phospho-NSAIDs in Ces1c-knockout mice. METHODS:
      Hydrolysis of phospho-NSAIDs by Ces1c was investigated using Ces1c-overexpressing
      cells. The rate of phospho-NSAID hydrolysis was compared between wild-type,
      Ces1c+/- and Ces1c-/- mouse plasma in vitro, and the effect of plasma Ces1c on
      the cytotoxicity of phospho-NSAIDs was evaluated. Pharmacokinetics of phospho
      sulindac was examined in wild-type and Ces1c-/- mice. The impact of Ces1c on the
      efficacy of phospho-sulindac was investigated using lung and pancreatic cancer
      models in vivo. RESULTS: Phospho-NSAIDs were extensively hydrolyzed in Ces1c
      overexpressing cells. Phospho-NSAID hydrolysis in wild-type mouse plasma was 6
      530-fold higher than that in the plasma of Ces1c-/- mice. Ces1c-expressing wild
      type mouse serum attenuated the in vitro cytotoxicity of phospho-NSAIDs towards
      cancer cells. Pharmacokinetic studies of phospho-sulindac using wild-type and
      Ces1c-/- mice demonstrated 2-fold less inactivation of phospho-sulindac in the
      latter. Phospho-sulindac was 2-fold more efficacious in inhibiting the growth of
      lung and pancreatic carcinoma in Ces1c -/- mice, as compared to wild-type mice.
      CONCLUSIONS: Our results indicate that intact phospho-NSAIDs are the
      pharmacologically active entities and phospho-NSAIDs are expected to be more
      efficacious in humans than in rodents due to their differential expression of
      carboxylesterases.

PMID- 25392230
TI  - Fractional thermolysis by bipolar radiofrequency facilitates cutaneous delivery
      of peptide and siRNA with minor loss of barrier function.
AB  - PURPOSE: In this study, we aimed to illustrate the utility of fractional
      radiofrequency (RF) that generated microchannels in the skin, allowing delivery
      of peptide and siRNA via the skin. The mechanisms involved in the correlation
      between macromolecule permeation and skin structure were also elucidated.
      METHODS: The morphology of the skin was examined by transmission electron
      microscopy (TEM), higher harmonic generation microscopy (HGM), and physiological
      factors. In vivo skin distribution of macromolecules was assessed by fluorescence
      and confocal microscopies. RESULTS: RF thermolysis selectively created an array
      of micropores deep into the epidermis without significant removal of the stratum
      corneum (SC). With energy of 30 mJ, a pore depth of 35 MUm was achieved. The
      bipolar RF resulted in a 3-fold increase of transepidermal water loss (TEWL)
      compared with intact skin. The respective skin accumulation and flux of the
      peptide with a molecular weight (MW) of 2335 Da was 3- and 23-fold greater for
      the RF-treated group than for the non-treatment group. RF enhanced skin
      accumulation of siRNAs with MW of 10 and 15 kDa by 6.2- and 2.6-fold,
      respectively. Cutaneous penetration of the macromolecules with an MW of at least
      40 kDa could be accomplished by RF. Confocal microscopy imaging revealed that RF
      could effectively deliver the peptide up to at least a 74-MUm depth. The
      penetration depth of siRNA by RF irradiation was about 50 MUm. CONCLUSIONS: The
      novel RF device efficiently delivered macromolecules into the skin while
      reserving SC layers to support some barrier functions. In this work, for the
      first time the assistance of fractional RF on peptide and siRNA transport was
      demonstrated.

PMID- 25392231
TI  - Myocardial tissue CO2 tension detects coronary blood flow reduction after
      coronary artery bypass in real-time?.
AB  - BACKGROUND: Coronary stenosis after coronary artery bypass grafting (CABG) may
      lead to myocardial ischaemia and is clinically difficult to diagnose. In a CABG
      model, we aimed at defining variables that detect hypoperfusion in real-time and
      correlate with impaired regional ventricular function by monitoring myocardial
      tissue metabolism. METHODS: Off-pump CABG was performed in 10 pigs. Graft blood
      flow was reduced in 18 min intervals to 75, 50, and 25% of baseline flow with
      reperfusion between each flow reduction. Myocardial tissue Pco2 (Pt(CO2)), Po2,
      pH, glucose, lactate, and glycerol from the graft supplied region and a control
      region were obtained. Regional cardiac function was assessed as radial strain.
      RESULTS: In comparison with baseline, myocardial pH decreased during 75, 50, and
      25% flow reduction (-0.15; -0.22; -0.37, respectively, all P<0.05) whereas
      Pt(CO2) increased (+4.6 kPa; +7.8 kPa; +12.9 kPa, respectively, all P<0.05). pH
      and Pt(CO2) returned to baseline upon reperfusion. Lactate and glycerol increased
      flow-dependently, while glucose decreased. Regional ventricular contractile
      function declined significantly. All measured variables remained normal in the
      control region. Pt(CO2) correlated strongly with tissue lactate, pH, and
      contractile function (R=0.86, R=-0.91, R=-0.70, respectively, all P<0.001). New
      conductometric Pt(CO2) sensors were in agreement with established fibre-optic
      probes. Cardiac output was not altered. CONCLUSIONS: Myocardial pH and Pt(CO2)
      monitoring can quantify the degree of regional tissue hypoperfusion in real-time
      and correlated well with cellular metabolism and contractile function, whereas
      cardiac output did not. New robust conductometric Pt(CO2) sensors have the
      potential to serve as a clinical cardiac monitoring tool during surgery and
      postoperatively.

PMID- 25392232
TI  - Molecular Mechanism for Hypertensive Renal Disease: Differential Regulation of
      Chromogranin A Expression at 3'-Untranslated Region Polymorphism C+87T by
      MicroRNA-107.
AB  - Chromogranin A (CHGA) is coreleased with catecholamines from secretory vesicles
      in adrenal medulla and sympathetic axons. Genetic variation in the CHGA 3'-region
      has been associated with autonomic control of circulation, hypertension, and
      hypertensive nephropathy, and the CHGA 3'-untranslated region (3'-UTR) variant
      C+87T (rs7610) displayed peak associations with these traits in humans. Here, we
      explored the molecular mechanisms underlying these associations. C+87T occurred
      in a microRNA-107 (miR-107) motif (match: T>C), and CHGA mRNA expression varied
      inversely with miR-107 abundance. In cells transfected with chimeric
      luciferase/CHGA 3'-UTR reporters encoding either the T allele or the C allele,
      changes in miR-107 expression levels had much greater effects on expression of
      the T allele. Cotransfection experiments with hsa-miR-107 oligonucleotides and
      eukaryotic CHGA plasmids produced similar results. Notably, an in vitro CHGA
      transcription/translation experiment revealed that changes in hsa-miR-107
      expression altered expression of the T allele variant only. Mice with targeted
      ablation of Chga exhibited greater eGFR. Using BAC transgenesis, we created a
      mouse model with a humanized CHGA locus (T/T genotype at C+87T), in which
      treatment with a hsa-miR-107 inhibitor yielded prolonged falls in SBP/DBP
      compared with wild-type mice. We conclude that the CHGA 3'-UTR C+87T disrupts an
      miR-107 motif, with differential effects on CHGA expression, and that a cis:trans
      (mRNA:miR) interaction regulates the association of CHGA with BP and hypertensive
      nephropathy. These results indicate new strategies for probing autonomic
      circulatory control and ultimately, susceptibility to hypertensive renal
      sequelae.

PMID- 25392234
TI  - Do it yourself guide to genome assembly.
AB  - Bioinformatics skills required for genome sequencing often represent a
      significant hurdle for many researchers working in computational biology. This
      humble effort highlights the significance of genome assembly as a research area,
      focuses on its need to remain accurate, provides details about the
      characteristics of the raw data, examines some key metrics, emphasizes some tools
      and draws attention to a generic tutorial with example data that outlines the
      whole pipeline for next-generation sequencing. The article concludes by pointing
      out some major future research problems. 

PMID- 25392233
TI  - GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting
      TGF-beta-Induced Smad3 Phosphorylation.
AB  - TGF-beta1, via Smad-dependent or Smad-independent signaling, has a central role
      in the pathogenesis of renal fibrosis. This pathway has been recognized as a
      potential target for antifibrotic therapy. Here, we identified GQ5, a small
      molecular phenolic compound isolated from the dried resin of Toxicodendron
      vernicifluum, as a potent and selective inhibitor of TGF-beta1-induced Smad3
      phosphorylation. In TGF-beta1-stimulated renal tubular epithelial cells and
      interstitial fibroblast cells, GQ5 inhibited the interaction of Smad3 with TGF
      beta type I receptor (TbetaRI) by blocking binding of Smad3 to SARA, suppressed
      subsequent phosphorylation of Smad3, reduced nuclear translocation of Smad2,
      Smad3, and Smad4, and downregulated the transcription of major fibrotic genes
      such as alpha-smooth muscle actin (alpha-SMA), collagen I, and fibronectin.
      Notably, intraperitoneal administration of GQ5 in rats immediately after
      unilateral ureteral obstruction (UUO) selectively inhibited Smad3 phosphorylation
      in UUO kidneys, suppressed renal expression of alpha-SMA, collagen I, and
      fibronectin, and resulted in impressive renal protection after obstructive
      injury. Late administration of GQ5 also effectively attenuated fibrotic lesions
      in obstructive nephropathy. In conclusion, our results suggest that GQ5 hinders
      renal fibrosis in rats by selective inhibition of TGF-beta1-induced Smad3
      phosphorylation.

PMID- 25392237
TI  - Is Antibiotic Prophylaxis for Percutaneous Radiofrequency Ablation (RFA) of
      Primary Liver Tumors Necessary? Results From a Single-Center Experience.
AB  - PURPOSE: The purpose of this study was to evaluate need for antibiotic
      prophylaxis for radiofrequency ablation (RFA) of liver tumors in patients with no
      significant co-existing risk factors for infection. MATERIALS AND METHODS: From
      January 2004 to September 2013, 83 patients underwent 123 percutaneous RFA
      procedures for total of 152 hepatocellular carcinoma (HCC) lesions. None of the
      patients had pre-existing biliary enteric anastomosis (BEA) or any biliary tract
      abnormality predisposing to ascending biliary infection or uncontrolled diabetes
      mellitus. No pre- or post-procedure antibiotic prophylaxis was provided for 121
      procedures. Data for potential risk factors were reviewed retrospectively and
      analyzed for the frequency of infectious complications, including abscess
      formation. RESULTS: One patient (1/121 (0.8%) RFA sessions) developed a large
      segment 5 liver abscess/infected biloma communicating with the gallbladder 7
      weeks after the procedure, successfully treated over 10 weeks with IV and PO
      antibiotic therapy and percutaneous catheter drainage. This patient did not
      receive any antibiotics prior to RFA. During the procedure, there was inadvertent
      placement of RFA probe tines into the gallbladder. No other infectious
      complications were documented. CONCLUSION: These data suggest that the routine
      use of prophylactic antibiotics for liver RFA is not necessary in majority of the
      patients undergoing liver ablation for HCC and could be limited to patients with
      high-risk factors such as the presence of BEA or other biliary abnormalities,
      uncontrolled diabetes mellitus, and large centrally located tumors in close
      proximity to central bile ducts. Larger randomized studies are needed to confirm
      this hypothesis.

PMID- 25392235
TI  - Clinical Recommendations for the Use of Islet Cell Autoantibodies to Distinguish
      Autoimmune and Non-Autoimmune Gestational Diabetes.
AB  - Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that
      begins or is first recognized during pregnancy. The prevalence of GDM is highly
      variable, depending on the population studied, and reflects the underlying
      pattern of diabetes in the population. GDM manifests by the second half of
      pregnancy and disappears following delivery in most cases, but is associated with
      the risk of subsequent diabetes development. Normal pregnancy induces
      carbohydrate intolerance to favor the availability of nutrients for the fetus,
      which is compensated by increased insulin secretion from the maternal pancreas.
      Pregnancy shares similarities with adiposity in metabolism to save energy, and
      both conditions favor the development of insulin resistance (IR) and low-grade
      inflammation. A highly complicated network of modified regulatory mechanisms may
      primarily affect carbohydrate metabolism by promoting autoimmune reactions to
      pancreatic beta cells and affecting insulin function. As a result, diabetes
      development during pregnancy is facilitated. Depending on a pregnant woman's
      genetic susceptibility to diabetes, autoimmune mechanisms or IR are fundamental
      to the development autoimmune or non-autoimmune GDM, respectively. Pregnancy may
      facilitate the identification of women at risk of developing diabetes later in
      life; autoimmune and non-autoimmune GDM may be early markers of the risk of
      future type 1 and type 2 diabetes, respectively. The most convenient and
      efficient way to discriminate GDM types is to assess pancreatic beta-cell
      autoantibodies along with diagnosing diabetes in pregnancy. 

PMID- 25392236
TI  - VBP15, a novel anti-inflammatory, is effective at reducing the severity of murine
      experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis is a chronic disease of the central nervous system
      characterized by an autoimmune inflammatory reaction that leads to axonal
      demyelination and tissue damage. Glucocorticoids, such as prednisolone, are
      effective in the treatment of multiple sclerosis in large part due to their
      ability to inhibit pro-inflammatory pathways (e.g., NFkappaB). However, despite
      their effectiveness, long-term treatment is limited by adverse side effects.
      VBP15 is a recently described compound synthesized based on the lazeroid
      steroidal backbone that shows activity in acute and chronic inflammatory
      conditions, yet displays a much-reduced side effect profile compared to
      traditional glucocorticoids. The purpose of this study was to determine the
      effectiveness of VBP15 in inhibiting inflammation and disease progression in
      experimental autoimmune encephalomyelitis (EAE), a widely used mouse model of
      multiple sclerosis. Our data show that VBP15 is effective at reducing both
      disease onset and severity. In parallel studies, we observed that VBP15 was able
      to inhibit the production of NFkappaB-regulated pro-inflammatory transcripts in
      human macrophages. Furthermore, treatment with prednisolone-but not VBP15
      increased expression of genes associated with bone loss and muscle atrophy,
      suggesting lack of side effects of VBP15. These findings suggest that VBP15 may
      represent a potentially safer alternative to traditional glucocorticoids in the
      treatment of multiple sclerosis and other inflammatory diseases. 

PMID- 25392238
TI  - Recommendations for validation of LC-MS/MS bioanalytical methods for protein
      biotherapeutics.
AB  - This paper represents the consensus views of a cross-section of companies and
      organizations from the USA and Canada regarding the validation and application of
      liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for bioanalysis
      of protein biotherapeutics in regulated studies. It was prepared under the
      auspices of the AAPS Bioanalytical Focus Group's Protein LC-MS Bioanalysis
      Subteam and is intended to serve as a guide to drive harmonization of best
      practices within the bioanalytical community and provide regulators with an
      overview of current industry thinking on applying LC-MS/MS technology for protein
      bioanalysis. For simplicity, the scope was limited to the most common current
      approach in which the protein is indirectly quantified using LC-MS/MS measurement
      of one or more of its surrogate peptide(s) produced by proteolytic digestion.
      Within this context, we considered a range of sample preparation approaches from
      simple in-matrix protein denaturation and digestion to complex procedures
      involving affinity capture enrichment. Consideration was given to the method
      validation experiments normally associated with traditional LC-MS/MS and ligand
      binding assays. Our collective experience, thus far, is that LC-MS/MS methods for
      protein bioanalysis require different development and validation considerations
      than those used for small molecules. The method development and validation plans
      need to be tailored to the particular assay format being established, taking into
      account a number of important factors: the intended use of the assay, the test
      species or study population, the characteristics of the protein biotherapeutic
      and its similarity to endogenous proteins, potential interferences, as well as
      the nature, quality, and availability of reference and internal standard
      materials.

PMID- 25392239
TI  - Preparation and long-term biodistribution studies of a PAMAM dendrimer G5-Gd
      BnDOTA conjugate for lymphatic imaging.
AB  - AIMS: To demonstrate the use of gadolinium (Gd)-labeled dendrimers as lymphatic
      imaging agents and establish the long-term biodistribution (90-day) of this type
      of agent in mice. MATERIALS & METHODS: A G5-Gd-BnDOTA dendrimer was prepared and
      injected into mice and monkeys for MR lymphangiography, and long-term
      biodistribution of the conjugate was studied. RESULTS: Administration of G5-Gd
      BnDOTA in mice demonstrated a rapid uptake in the deep lymphatic system while
      injection in monkeys showed enhanced internal iliac nodes, indicating its general
      utility for lymphatic tracking. Biodistribution studies to 90 days showed that
      gadolinium conjugate is slowly being eliminated from the liver and other organs.
      CONCLUSION: The use of G5-Gd-BnDOTA holds great promise for lymphatic imaging,
      but its slow clearance from the body might hamper its eventual clinical
      translation.

PMID- 25392240
TI  - Effects of salicylate on sound-evoked outer hair cell stereocilia deflections.
AB  - Hearing depends on sound-evoked deflections of the stereocilia that protrude from
      the sensory hair cells in the inner ear. Although sound provides an important
      force driving stereocilia, forces generated through mechanically sensitive ion
      channels and through the motor protein prestin have been shown to influence
      stereocilia motion in solitary hair cells. While a possible influence of prestin
      on mechanically sensitive ion channels has not been systematically investigated,
      a decrease in transducer currents is evident in solitary hair cells when prestin
      is blocked with salicylate, raising the question of whether a reduced prestin
      activity or salicylate itself affected the mechanotransduction apparatus. We used
      two- and three-dimensional time-resolved confocal imaging to visualize outer hair
      cell stereocilia during sound stimulation in the apical turn of cochlear explant
      preparations from the guinea pig. Surprisingly, following application of
      salicylate, outer hair cell stereocilia deflections increased, while cochlear
      microphonic potentials decreased. However, when prestin activity was altered with
      the chloride ionophore tributyltin, both the cochlear microphonic potential and
      the stereocilia deflection amplitude decreased. Neither positive nor negative
      current stimulation abolished the bundle movements in the presence of salicylate,
      indicating that the observed effects did not depend on the endocochlear
      potential. These data suggest that salicylate may alter the mechanical properties
      of stereocilia, decreasing their bending stiffness. 

PMID- 25392241
TI  - Connective tissue growth factor modulates adult beta-cell maturity and
      proliferation to promote beta-cell regeneration in mice.
AB  - Stimulation of endogenous beta-cell expansion could facilitate regeneration in
      patients with diabetes. In mice, connective tissue growth factor (CTGF) is
      expressed in embryonic beta-cells and in adult beta-cells during periods of
      expansion. We discovered that in embryos CTGF is necessary for beta-cell
      proliferation, and increased CTGF in beta-cells promotes proliferation of
      immature (MafA(-)) insulin-positive cells. CTGF overexpression, under
      nonstimulatory conditions, does not increase adult beta-cell proliferation. In
      this study, we tested the ability of CTGF to promote beta-cell proliferation and
      regeneration after partial beta-cell destruction. beta-Cell mass reaches 50%
      recovery after 4 weeks of CTGF treatment, primarily via increased beta-cell
      proliferation, which is enhanced as early as 2 days of treatment. CTGF treatment
      increases the number of immature beta-cells but promotes proliferation of both
      mature and immature beta-cells. A shortened beta-cell replication refractory
      period is also observed. CTGF treatment upregulates positive cell-cycle
      regulators and factors involved in beta-cell proliferation, including hepatocyte
      growth factor, serotonin synthesis, and integrin beta1. Ex vivo treatment of
      whole islets with recombinant human CTGF induces beta-cell replication and gene
      expression changes consistent with those observed in vivo, demonstrating that
      CTGF acts directly on islets to promote beta-cell replication. Thus, CTGF can
      induce replication of adult mouse beta-cells given a permissive microenvironment.

PMID- 25392243
TI  - Targeted allelic expression profiling in human islets identifies cis-regulatory
      effects for multiple variants identified by type 2 diabetes genome-wide
      association studies.
AB  - Genome-wide association studies (GWAS) have identified variation at >65 genomic
      loci associated with susceptibility to type 2 diabetes, but little progress has
      been made in elucidating the molecular mechanisms behind most of these
      associations. Using samples heterozygous for transcribed single nucleotide
      polymorphisms (SNPs), allelic expression profiling is a powerful technique for
      identifying cis-regulatory variants controlling gene expression. In this study,
      exonic SNPs, suitable for measuring mature mRNA levels and in high linkage
      disequilibrium with 65 lead type 2 diabetes GWAS SNPs, were identified and
      allelic expression determined by real-time PCR using RNA and DNA isolated from
      islets of 36 white nondiabetic donors. A significant allelic expression imbalance
      (AEI) was identified for 7/14 (50%) genes tested (ANPEP, CAMK2B, HMG20A, KCNJ11,
      NOTCH2, SLC30A8, and WFS1), with significant AEI confirmed for five of these
      genes using other linked exonic SNPs. Lastly, results of a targeted islet
      expression quantitative trait loci experiment support the AEI findings for ANPEP,
      further implicating ANPEP as the causative gene at its locus. The results of this
      study support the hypothesis that changes to cis-regulation of gene expression
      are involved in a large proportion of SNP associations with type 2 diabetes
      susceptibility. 

PMID- 25392242
TI  - Evidence of early alterations in adipose tissue biology and function and its
      association with obesity-related inflammation and insulin resistance in children.
AB  - Accumulation of fat mass in obesity may result from hypertrophy and/or
      hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in
      adults. Here we assessed early alterations in AT biology and function by
      comprehensive experimental and clinical characterization of 171 AT samples from
      lean and obese children aged 0 to 18 years. We show an increase in adipocyte size
      and number in obese compared with lean children beginning in early childhood.
      These alterations in AT composition in obese children were accompanied by
      decreased basal lipolytic activity and significantly enhanced stromal vascular
      cell proliferation in vitro, potentially underlying the hypertrophy and
      hyperplasia seen in obese children, respectively. Furthermore, macrophage
      infiltration, including the formation of crown-like structures, was increased in
      AT of obese children from 6 years on and was associated with higher hs-CRP serum
      levels. Clinically, adipocyte hypertrophy was not only associated with leptin
      serum levels but was highly and independently correlated with HOMA-IR as a marker
      of insulin resistance in children. In summary, we show that adipocyte hypertrophy
      is linked to increased inflammation in AT in obese children, thereby providing
      evidence that obesity-associated AT dysfunction develops in early childhood and
      is related to insulin resistance. 

PMID- 25392245
TI  - Diabetes enhances the proliferation of adult pancreatic multipotent progenitor
      cells and biases their differentiation to more beta-cell production.
AB  - Endogenous pancreatic multipotent progenitors (PMPs) are ideal candidates for
      regenerative approaches to compensate for beta-cell loss since their beta-cell
      producing capacities as well as strategic location would eliminate unnecessary
      invasive manipulations. However, little is known about the status and potentials
      of PMPs under diabetic conditions. Here we show that beta-cell metabolic stress
      and hyperglycemia enhance the proliferation capacities of adult PMP cells and
      bias their production of progeny toward beta-cells in mouse and human. These
      effects are dynamic and correlate with functional beta-cell regeneration when
      conditions allow. 

PMID- 25392244
TI  - Perilipin 5 regulates islet lipid metabolism and insulin secretion in a cAMP
      dependent manner: implication of its role in the postprandial insulin secretion.
AB  - Elevation of circulating fatty acids (FA) during fasting supports postprandial
      (PP) insulin secretion that is critical for glucose homeostasis and is impaired
      in diabetes. We tested our hypothesis that lipid droplet (LD) protein perilipin 5
      (PLIN5) in beta-cells aids PP insulin secretion by regulating intracellular lipid
      metabolism. We demonstrated that PLIN5 serves as an LD protein in human islets.
      In vivo, Plin5 and triglycerides were increased by fasting in mouse islets. MIN6
      cells expressing PLIN5 (adenovirus [Ad]-PLIN5) and those expressing perilipin 2
      (PLIN2) (Ad-PLIN2) had higher [(3)H]FA incorporation into triglycerides than Ad
      GFP control, which support their roles as LD proteins. However, Ad-PLIN5 cells
      had higher lipolysis than Ad-PLIN2 cells, which increased further by 8-Br-cAMP,
      indicating that PLIN5 facilitates FA mobilization upon cAMP stimulation as seen
      postprandially. Ad-PLIN5 in islets enhanced the augmentation of glucose
      stimulated insulin secretion by FA and 8-Br-cAMP in G-protein-coupled receptor 40
      (GPR40)- and cAMP-activated protein kinase-dependent manners, respectively. When
      PLIN5 was increased in mouse beta-cells in vivo, glucose tolerance after an acute
      exenatide challenge was improved. Therefore, the elevation of islet PLIN5 during
      fasting allows partitioning of FA into LD that is released upon refeeding to
      support PP insulin secretion in cAMP- and GPR40-dependent manners. 

PMID- 25392247
TI  - From the editors.

PMID- 25392246
TI  - Viral infection of engrafted human islets leads to diabetes.
AB  - Type 1 diabetes (T1D) is characterized by the destruction of the insulin
      producing beta-cells of pancreatic islets. Genetic and environmental factors both
      contribute to T1D development. Viral infection with enteroviruses is a suspected
      trigger for T1D, but a causal role remains unproven and controversial. Studies in
      animals are problematic because of species-specific differences in host cell
      susceptibility and immune responses to candidate viral pathogens such as
      coxsackievirus B (CVB). In order to resolve the controversial role of viruses in
      human T1D, we developed a viral infection model in immunodeficient mice bearing
      human islet grafts. Hyperglycemia was induced in mice by specific ablation of
      native beta-cells. Human islets, which are naturally susceptible to CVB
      infection, were transplanted to restore normoglycemia. Transplanted mice were
      infected with CVB4 and monitored for hyperglycemia. Forty-seven percent of CVB4
      infected mice developed hyperglycemia. Human islet grafts from infected mice
      contained viral RNA, expressed viral protein, and had reduced insulin levels
      compared with grafts from uninfected mice. Human-specific gene expression
      profiles in grafts from infected mice revealed the induction of multiple
      interferon-stimulated genes. Thus, human islets can become severely dysfunctional
      with diminished insulin production after CVB infection of beta-cells, resulting
      in diabetes. 

PMID- 25392248
TI  - Convergent validity of the ASAM criteria in co-occurring disorders.
AB  - OBJECTIVE: The complexity of substance use and psychiatric disorders demands
      thorough assessment of patients for integrated services. We tested the convergent
      validity of the software version of the American Society of Addiction Medicine
      (ASAM) second edition-revised criteria for patient placement by examining the
      software's ability to discriminate based on a variety of demographic and clinical
      factors. METHODS: This prospective naturalistic multi-site study examined the
      software's assignment of patients to three types of treatment (addiction only
      services, dual diagnosis capable, and dual diagnosis enhanced) and whether these
      assignments indicated an ability to discriminate between patients with and
      without dual diagnosis based on clinical characteristics and severity. Ten
      addiction treatment clinics spanning three counties participated, and both
      patients and ASAM assessors were kept blind to the ASAM recommendation. Patients
      were assigned to their respective treatment options based on routine assessment
      by clinicians at intake, which they had in addition to the ASAM interview. Three
      months after treatment initiation a follow-up interview with ASAM was conducted.
      RESULTS: There were 261 patients in the study, 96 (36.7%) were assigned to
      addiction only services, 42 (16.1%) to dual diagnosis capable, and 123 (47.1%) to
      dual diagnosis enhanced. Patients assigned to the two dual diagnosis groups were
      significantly more likely to be younger and have fewer years of work than other
      patients. There were significant differences in history of inpatient and
      outpatient psychiatric treatment across groups. For example, a larger percentage
      of those in addiction only services had never been in inpatient treatment, while
      more of those in the two dual diagnosis groups had three or more inpatient stays.
      Despite similar alcohol and drug severity scores, patients recommended by the
      software for dual diagnosis enhanced programs showed a gradient of significantly
      higher psychiatric (p <.001), legal (p <.04), and family (p <.001) Addiction
      Severity Index composite scores at baseline than patients in dual diagnosis
      capable and addiction only services. CONCLUSIONS: RESULTS show a high prevalence
      of co-occurring program recommendations with statistically significant and
      clinically meaningful differences between patient groups. The convergent validity
      of the revised version of ASAM Criteria Software is supported by these results.

PMID- 25392249
TI  - Clinical characteristics of individuals with schizophrenia and hallucinogen
      persisting perception disorder: a preliminary investigation.
AB  - OBJECTIVE: An unusual side effect of hallucinogen use is the appearance of
      hallucinogen persisting perception disorder (HPPD). Despite high rates of prior
      hallucinogen use among individuals with schizophrenia, there are insufficient
      data on the clinical characteristics of individuals with co-occurring
      schizophrenia and HPPD. METHODS: Twenty-six hospitalized patients with
      schizophrenia and prior LSD use (12 with HPPD and 14 without HPPD) were
      recruited. Participants were clinically assessed using validated tools, and
      details regarding hospitalizations were retrieved from their medical records.
      Those patients who also had HPPD completed a questionnaire addressing HPPD
      associated perceptual disturbances. RESULTS: Participants were mostly male (n =
      22, 84.6%) and had an average age of 32.3 (SD = 7.67). Nearly half (n = 12,
      46.2%) met criteria for HPPD. No significant differences were found in
      sociodemographic and clinical characteristics (including response to
      antipsychotic medications and adverse effects) between the groups. Nine
      individuals (75%) in the schizophrenia and HPPD group reported the ability to
      identify specific precursory cues for the appearance of the HPPD-associated
      perceptual distortions, and 8 (67%) reported the ability to distinguish HPPD
      perceptual disturbances from those associated with their psychotic disorder.
      CONCLUSIONS: Very little is known about the co-occurrence of schizophrenia and
      HPPD or the associated clinical implications. Further research is needed to
      understand the clinical impact of this comorbidity.

PMID- 25392250
TI  - Dual diagnosis resource needs in Spain: a national survey of professionals.
AB  - OBJECTIVE: Since provision of integrated services for patients with dual
      pathology or dual disorders (coexistence of an addictive disorder and another
      mental health disorder) is an important challenge in mental health, this study
      assessed health care professionals' perceptions and knowledge of the current
      state of specific resources for patients with dual pathology in Spain. METHODS:
      We conducted a national survey of health care professionals seeing patients with
      dual pathology in treatment facilities throughout Spain. Participants completed a
      specific online questionnaire about the needs of and available resources for
      patients with dual pathology. RESULTS: A total of 659 professionals, mostly
      psychologists (n = 286, 43.4%) or psychiatrists (n = 217, 32.9%), participated in
      the study. Nearly all participants who responded to these items reported that
      specific resources for dual pathology were needed (n = 592/635, 93.2%); 76.7% (n
      = 487) identified intermediate resources, 68.8% (n = 437) acute detoxification
      units, and 64.6% (n = 410) medium-stay rehabilitation units as particularly
      necessary. In the opinion of 54.0% of respondents (n = 343), integrated mental
      health and addiction treatment services were available. Of the participants who
      answered these items, only a small proportion (n = 162/605, 26.8%) reported that
      there were appropriate outpatient programs for dual pathology, 30.4% (n =
      184/605) specific hospitalization units, 16.9% (n = 99/587) subacute inpatient
      units, 34.2% (n = 201/587) outpatient intermediate resources, 15.5% (n = 91/587)
      day hospitals, and 21.5% (n = 126/587) day centers. Conversely, 62.5% (n =
      378/587) of participants reported a greater presence of specific
      detoxification/withdrawal units, 47.3% (n = 286/587) psychiatric acute admission
      units, and 41.9% (n = 246/587) therapeutic communities. In the professionals'
      opinion, the presence of specialty programs was low; 11.6% of respondents (n =
      68/587) reported that vocational programs and 16.7% (n = 98/587) reported that
      occupational rehabilitation programs were available. Employee turnover was
      common: 51.9% of respondents (n = 314/605) stated that employee turnover was
      occasional to frequent. CONCLUSIONS: According to the professionals surveyed,
      specific health care resources for the management of dual pathology are currently
      insufficient, underlining the need for additional efforts and strategies for
      treating individuals with comorbid disorders.

PMID- 25392251
TI  - Domains and perceived benefits of treatment among patients with and without co
      occurring disorders in inpatient substance use treatment.
AB  - OBJECTIVE: Persons with substance use disorders often have comorbid psychiatric
      problems, and treating all problem domains is important for treatment success and
      recovery. This study examined reported interventions provided to patients as well
      as patients' reports of domains of help received, perceived areas of greatest
      benefit, and satisfaction with substance use disorder treatment. We also compared
      patients with co-occurring disorders and patients with only substance use
      disorders to see whether there were significant differences across groups on
      these measures. METHODS: Patients receiving inpatient substance use treatment at
      clinics in Norway were recruited for the study; 85 completed a cross-sectional
      survey prior to discharge. Treatment personnel also completed a separate survey
      and gathered information from patient charts. RESULTS: The most frequently
      provided treatment interventions involved improving relationships with family and
      important others, applied relaxation, psychodynamic therapy, cognitive behavior
      therapy, and motivational interviewing. Patients reported receiving the most help
      in domains of relapse prevention, physical health, daily functioning,
      relationships with people, psychological health, and self-esteem. They benefited
      most from physical activities, support from co-patients, group therapy,
      counseling, and assessment/treatment of psychological health. Patients with co
      occurring disorders were given more exposure therapy, motivational interviewing,
      and cognitive behavior therapy interventions than those without comorbidity.
      Patients with co-occurring disorders self-reported receiving more help with self
      esteem and coping with psychiatric symptoms and benefiting more from
      interventions involving psychological health, acute help, and social situations.
      CONCLUSIONS: Patients perceived psychological and physical health as important
      areas for improvement. There were differences between patients with co-occurring
      disorders and those with substance use disorders only in several measures. It is
      important to acknowledge that patients with substance use disorders and co
      occurring mental problems are heterogeneous groups with unique but overlapping
      needs.

PMID- 25392252
TI  - Cocaine-induced psychotic disorders: presentation, mechanism, and management.
AB  - Cocaine, the third mostly commonly used illicit drug in the United States, has a
      wide range of neuropsychiatric effects, including transient psychotic symptoms.
      When psychotic symptoms occur within a month of cocaine intoxication or
      withdrawal, the diagnosis is cocaine-induced psychotic disorder (CIPD). Current
      evidence suggests those with CIPD are likely to be male, have longer severity and
      duration of cocaine use, use intravenous cocaine, and have a lower body mass
      index. Differentiating CIPD from a primary psychotic disorder requires a detailed
      history of psychotic symptoms in relation to substance use and often a
      longitudinal assessment. Treatment includes providing a safe environment,
      managing agitation and psychosis, and addressing the underlying substance use
      disorder. This review begins with a clinical case and summarizes the literature
      on CIPD, including clinical presentation, differential diagnosis, mechanism and
      predictors of illness, and treatment. 

PMID- 25392253
TI  - Systematic implementation of clinical risk management in a large university
      hospital: the impact of risk managers.
AB  - BACKGROUND: For health care systems in recent years, patient safety has
      increasingly become a priority issue. National and international strategies have
      been considered to attempt to overcome the most prominent hazards while patients
      are receiving health care. Thereby, clinical risk management (CRM) plays a
      dominant role in enabling the identification, analysis, and management of
      potential risks. CRM implementation into routine procedures within complex
      hospital organizations is challenging, as in the past, organizational change
      strategies using a top-down approach have often failed. Therefore, one of our
      main objectives was to educate a certain number of risk managers in facilitating
      CRM using a bottom-up approach. METHODS: To achieve our primary purpose, five
      project strands were developed, and consequently followed, introducing CRM:
      corporate governance, risk management (RM) training, CRM process, information,
      and involvement. The core part of the CRM process involved the education of risk
      managers within each organizational unit. To account for the size of the existing
      organization, we assumed that a minimum of 1 % of the workforce had to be trained
      in RM to disseminate the continuous improvement of quality and safety. Following
      a roll-out plan, CRM was introduced in each unit and potential risks were
      identified. RESULTS: Alongside the changes in the corporate governance, a
      hospital-wide CRM process was introduced resulting in 158 trained risk managers
      correlating to 2.0 % of the total workforce. Currently, risk managers are present
      in every unit and have identified 360 operational risks. Among those, 176 risks
      were scored as strategic and clustered together into top risks. Effective meeting
      structures and opportunities to share information and knowledge were introduced.
      Thus far, 31 units have been externally audited in CRM. CONCLUSION: The CRM
      approach is unique with respect to its dimension; members of all health care
      professions were trained to be able to identify potential risks. A network of
      risk managers supported the centrally coordinated CRM process. There is a strong
      commitment among management, academia, clinicians, and administration to foster
      cooperation. The introduction of CRM led to a visible shift with regard to
      patient safety culture throughout the entire organization. Still, there is a long
      way to go to keep people engaged in CRM and work on national and international
      patient safety initiatives to continuously decrease potential hazards.

PMID- 25392254
TI  - HerzMobil Tirol network: rationale for and design of a collaborative heart
      failure disease management program in Austria.
AB  - Heart failure (HF) is approaching epidemic proportions worldwide and is the
      leading cause of hospitalization in the elderly population. High rates of
      readmission contribute substantially to excessive health care costs and highlight
      the fragmented nature of care available to HF patients. Disease management
      programs (DMPs) have been implemented to improve health outcomes, patient
      satisfaction, and quality of life, and to reduce health care costs.
      Telemonitoring systems appear to be effective in the vulnerable phase after
      discharge from hospital to prevent early readmissions. DMPs that emphasize
      comprehensive patient education and guideline-adjusted therapy have shown great
      promise to result in beneficial long-term effects. It can be speculated that
      combining core elements of the aforementioned programs may substantially improve
      long-term cost-effectiveness of patient management.We introduce a collaborative
      post-discharge HF disease management program (HerzMobil Tirol network) that
      incorporates physician-controlled telemonitoring and nurse-led care in a
      multidisciplinary network approach. 

PMID- 25392255
TI  - Senning operation for very low birth weight infant with transposition of the
      great arteries: one of the smallest cases in the world.
AB  - We report a case of a Senning operation for very low birth weight infant weighing
      1,168 g with transposition of the great arteries. The patient underwent a Senning
      operation on 62 days, 1,700 g after the first palliation. In this case, the
      orifice of the left anterior descending artery was located in sinus 1 (left
      posterior facing sinus), but we could not find orifices of both right coronary
      artery and left circumflex artery before the Senning operation. The surgical
      procedure of the Senning operation is typical one, but we used flesh
      autopericardial patch to cover the roof of the new pulmonary vein chamber to get
      an enough size. The patient recovered with no cardiac events after the repair. 

PMID- 25392256
TI  - The effect of body weight on the severity and clinical course of ulcerative
      colitis.
AB  - PURPOSE: Obesity is a risk factor for inflammatory diseases such as nonalcoholic
      steatohepatitis, pancreatitis, and Crohn's disease. The effect of being
      overweight or obese on the severity and clinical course of ulcerative colitis
      (UC) was assessed in a retrospective analysis of data from 2000-2006. METHODS:
      Two hundred and two consecutive UC patients were categorized according to body
      mass index (BMI). Patient and disease characteristics were compared between BMI
      categories using chi-square or Kruskal-Wallis tests. The percentage of patients
      with active UC, complications, steroid therapy, or immunosuppressive therapy was
      calculated for each group, and matched pair analyses were performed. RESULTS: Ten
      patients (5%) were underweight, 111 (55%) were normal weight, 54 (26.7%) were
      overweight, and 27 (13.4%) were obese. Pancolitis was inversely related to
      weight. BMI was also inversely correlated to disease severity, with a
      significantly smaller proportion of years with chronic active disease among
      overweight subjects versus normal-weight subjects (17.6 versus 23.9%, p = 0.05).
      More overweight than normal-weight patients had no chronic active disease in any
      year (66 versus 49%, p = 0.06), and the proportion of years with disease
      complications was higher in normal weight than in overweight subjects (1.8 versus
      0.4%, p = 0.08). Disease activity during 2000-2006 was higher for underweight
      versus normal-weight patients, and only 20% of underweight subjects had no
      hospital admission compared to 80% of normal-weight patients (p = 0.07).
      CONCLUSIONS: This first study to explore the influence of obesity on UC showed
      that high BMI had rather a favorable effect on the prognosis, whereas low BMI
      pointed to a more severe course of the disease.

PMID- 25392257
TI  - Unfavorable effect of small tumor size on cause-specific survival in stage IIA
      colon cancer, a SEER-based study.
AB  - BACKGROUND: We sought to determine the prognostic role of tumor size on cause
      specific survival (CSS) of patients with stage IIA colon cancer. METHODS:
      Surveillance, Epidemiology and End Results (SEER) database was utilized to
      identify patients with stage IIA colorectal cancer (examined lymph nodes >=12)
      diagnosed from 1988 to 2003. The prognostic effect of tumor size on CSS was
      evaluated by univariate and multivariate analyses. RESULTS: A total of 8775
      patients were enrolled in the analysis. The median follow-up time was 109 months.
      As determined by minimal P value method, tumor sizes of 2.5 and 6.0 cm were used
      as optimal cutoff value to divide the cohort. The 8-year CSS of colon cancer with
      tumor sizes <=2.5, 2.6-6.0, and >6.0 cm was 81.6, 86.2, and 86.7% respectively (P
      = 0.003). In the multivariate analysis of colon cancer, using <=2.5-cm tumors as
      reference, decreased hazard ratio (HR) of CSS was observed in 2.6-6.0 cm (HR,
      0.736; 95% confidence interval (CI), 0.599-0.905; P = 0.004) and >6.0 cm (HR,
      0.770; 95% CI, 0.619-0.958; P = 0.019) tumors. CONCLUSIONS: In stage IIA colon
      cancer, small tumor size represented a subset with decreased CSS. Further studies
      are merited to validate the unfavorable prognostic role of small tumor size in
      stage IIA colon cancer.

PMID- 25392258
TI  - Colorectal squamous cell carcinoma: a rare tumor with poor prognosis.
AB  - PURPOSE: Primary squamous cell carcinomas of the colon and rectum are extremely
      rare, with an incidence of less than 1% of colorectal malignancies. Our aim in
      this study was to evaluate patient characteristics, treatment strategy, and
      postoperative follow-up of patients with colorectal squamous cell carcinoma.
      METHODS: We reviewed our prospectively maintained colorectal cancer database for
      all patients who were diagnosed with colorectal squamous cell carcinoma between
      January 1990 and April 2009. RESULTS: Out of 5149 patients with colorectal
      malignancy, 11 patients (0.2%) met the study criteria. Median age at the time of
      diagnosis was 64. Median BMI was 28 kg/m2. The tumors were localized in the
      rectum (n = 8), right colon (n = 2), and sigmoid colon (n = 1). The pathologic
      stages of these tumors were I (n = 1), II (n = 4), III (n = 3), and IV (n = 3).
      Operations performed were abdominoperineal resection (n = 4), right colectomy (n
      = 2), total colectomy (n = 1), low anterior resection (n = 1), local excision (n
      = 1), sigmoidectomy (n=1) and end colostomy creation (n = 1). One patient
      received intraoperative radiotherapy. Postoperative chemotherapy was given to
      eight patients, and three patients received postoperative radiation therapy.
      Median follow-up after diagnosis was 42 months (12-96). Three patients developed
      recurrence after potentially curative surgery. Five patients died from metastatic
      disease during follow-up. CONCLUSION: Squamous colorectal cancer can be detected
      in any part of the colon, generally presents at a later stage, and is associated
      with a poor prognosis. Surgery is the mainstay of treatment. Various adjuvant
      chemoradiation treatments appear not to influence the outcome. Further cases need
      to be analyzed in order to find more effective treatment regimens.

PMID- 25392259
TI  - Tumor necrosis factor-alpha-induced microvascular endothelial cell
      hyperpermeability: role of intrinsic apoptotic signaling.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a pro-apoptotic cytokine, is involved in
      vascular hyperpermeability, tissue edema, and inflammation. We hypothesized that
      TNF-alpha induces microvascular hyperpermeability through the mitochondria
      mediated intrinsic apoptotic signaling pathway. Rat lung microvascular
      endothelial cells grown on Transwell inserts, chamber slides, or dishes were
      treated with recombinant TNF-alpha (10 ng/ml) in the presence or absence of a
      caspase-3 inhibitor, Z-DEVD-FMK (100 MUM). Fluorescein isothiocyanate (FITC)
      albumin (5 mg/ml) was used as a marker of monolayer permeability. Mitochondrial
      reactive oxygen species (ROS) was determined using dihydrorhodamine 123 and
      mitochondrial transmembrane potential using JC-1. The adherens junction integrity
      and actin cytoskeletal organization were studied using beta-catenin
      immunofluorescence and rhodamine phalloidin, respectively. Caspase-3 activity was
      measured fluorometrically. The pretreatment with Z-DEVD-FMK (100 MUM) attenuated
      TNF-alpha-induced (10 ng/ml) disruption of the adherens junctions, actin stress
      fiber formation, increased caspase-3 activity, and monolayer hyperpermeability (p
      < 0.05). TNF-alpha (10 ng/ml) treatment resulted in increased mitochondrial ROS
      formation and decreased mitochondrial transmembrane potential. Intrinsic
      apoptotic signaling-mediated caspase-3 activation plays an important role in
      regulating TNF-alpha-induced endothelial cell hyperpermeability.

PMID- 25392260
TI  - Critical difference applied to exercise-induced salivary testosterone and
      cortisol using enzyme-linked immunosorbent assay (ELISA): distinguishing
      biological from statistical change.
AB  - Due to its noninvasive, convenient, and practical nature, salivary testosterone
      (sal-T) and cortisol (sal-C) are frequently used in a clinical and applied
      setting. However, few studies report biological and analytical error and even
      fewer report the 'critical difference' which is the change required before a true
      biological difference can be claimed. It was hypothesized that (a) exercise would
      result in a statistically significant change in sal-C and sal-T and (b) the
      exercise-induced change would be within the critical difference for both salivary
      hormones. In study 1, we calculated the critical difference of sal-T and sal-C of
      18 healthy adult males aged 23.2 +/- 3.0 years every 60 min in a seated position
      over a 12-h period (08:00-20:00 hours [study 1]). As proof-of-concept, sal-C and
      sal-T was also obtained pre and at 5 and 60 min post a maximal exercise protocols
      in a separate group of 17 healthy males (aged 20.1 +/- 2.8 years [study 2]). The
      critical difference of sal-T calculated as 90 %. For sal-C, the critical
      difference was 148 % (study 1). Maximal exercise was associated with a
      statistically significant (p < 0.05) changes in sal-T and sal-C. However, these
      changes were all within the critical difference range. Results from this
      investigation indicate that a large magnitude of change for sal-C and sal-T is
      required before a biologically significant mean change can be claimed. Studies
      utilizing sal-T and sal-C should appreciate the critical difference of these
      measures and assess the biological significance of any statistical changes.

PMID- 25392261
TI  - Solving a novel confinement problem by spartaeine salticids that are predisposed
      to solve problems in the context of predation.
AB  - Intricate predatory strategies are widespread in the salticid subfamily
      Spartaeinae. The hypothesis we consider here is that the spartaeine species that
      are proficient at solving prey-capture problems are also proficient at solving
      novel problems. We used nine species from this subfamily in our experiments.
      Eight of these species (two Brettus, one Cocalus, three Cyrba, two Portia) are
      known for specialized invasion of other spiders' webs and for actively choosing
      other spiders as preferred prey ('araneophagy'). Except for Cocalus, these
      species also use trial and error to derive web-based signals with which they gain
      dynamic fine control of the resident spider's behaviour ('aggressive
      mimicry').The ninth species, Paracyrba wanlessi, is not araneophagic and instead
      specializes at preying on mosquitoes. We presented these nine species with a
      novel confinement problem that could be solved by trial and error. The test
      spider began each trial on an island in a tray of water, with an atoll
      surrounding the island. From the island, the spider could choose between two
      potential escape tactics (leap or swim), but we decided at random before the
      trial which tactic would fail and which tactic would achieve partial success. Our
      findings show that the seven aggressive-mimic species are proficient at solving
      the confinement problem by repeating 'correct' choices and by switching to the
      alternative tactic after making an 'incorrect' choice. However, as predicted,
      there was no evidence of C. gibbosus or P. wanlessi, the two non-aggressive-mimic
      species, solving the confinement problem. We discuss these findings in the
      context of an often-made distinction between domain-specific and domain-general
      cognition. 

PMID- 25392262
TI  - Corneal Biomechanical Characteristics in Patients with Behcet Disease.
AB  - AIM: To examine corneal biomechanical properties, intraocular pressure, and
      central corneal thickness in uveitic eyes with Behcet disease (BD) and to compare
      them with healthy controls. METHODS: This study included 40 eyes of 34 patients
      with ocular BD and 20 eyes of 20 healthy controls. Eyes with ocular BD were
      subdivided into active and inactive groups. Ocular response analyzer (ORA)
      measurements were performed on the 20 eyes of 16 patients with active BD (group
      1), 20 eyes of 18 patients with inactive BD (group 2), and 20 eyes of 20 healthy
      volunteers who served as the control group (group 3). Corneal hysteresis (CH),
      corneal resistance factor (CRF), intraocular pressure (Goldmann correlated
      [IOPg], and corneal compensated [IOPcc]) and central corneal thickness (CCT)
      values were recorded. RESULTS: Mean age of patients in groups 1, 2, and 3 was
      33.81 +/- 9.36, 32.38 +/- 9.08, and 31.05 +/- 5.85 years, respectively (p =
      0.76). Mean CH, CRF, IOPg, IOPcc, and CCT values in groups 1, 2, and 3 were [8.51
      +/- 1.88, 9.72 +/- 2.11, 19.87 +/- 2.92, 16.13 +/- 3.29, and 592.50 +/- 39.95],
      [8.46 +/- 1.82, 8.45 +/- 1.98, 15.89 +/- 2.68, 15.35 +/- 2.91, and 528.35 +/-
      19.18], and [8.47 +/- 1.48, 8.43 +/- 1.58, 15.59 +/- 2.74, 15.42 +/- 3.19, and
      526.30 +/- 18.21], respectively [(p1 = 0.040, 0.904, <0.001, 0.495 and <0.001 for
      CRF, CH, IOPg, IOPcc and CCT in group 1, respectively), (p2 = 0.989, 0.904,
      0.659, 0.989, and 0.989 for CRF, CH, IOPg, IOPcc and CCT in group 2,
      respectively), (p3 = 0.989, 0.904, 0.660, 0.989, and 0.989 for CRF, CH, IOPg,
      IOPcc and CCT in group 3, respectively)]. CONCLUSION: CRF, IOPg, and CCT values
      altered in active BD group when compared with inactive BD and control group (p <
      0.005). Further studies are required to establish the effects of BD on corneal
      biomechanical properties.

PMID- 25392263
TI  - Epidemiology and Associated Morbidity of Pterygium: A Large, Community-Based Case
      Control Study.
AB  - BACKGROUND: To evaluate the prevalence and risk factors of various conditions
      among patients with pterygium. METHODS: A retrospective observational case
      control study of 4,037 patients who were diagnosed with pterygium in the Central
      District of Clalit Health Services in Israel from 2000-2009. A total of 16,054
      randomly selected controls from the district HMO members. Personal, medical, and
      demographic information were extracted from patients' files. We calculated the
      prevalence of various ocular, systemic, and demographic conditions as risk
      factors for pterygium. RESULTS: The average age of pterygium patients was 58.4 +/
      14 years; 56.9% were male. A significant tendency to develop pterygium was found
      among individuals of lower socioeconomic status (p < 0.001) and in populations
      living in rural areas (p < 0.001). A logistic regression model adjusted to
      marital status, socio-economic class, and area of living was performed. The
      following conditions were significantly associated with pterygium: blepharitis
      (OR = 1.71; 99.9% CI: 1.53-1.93), chalazia (OR = 1.46; 99.9% CI: (1.19-1.78)),
      anxiety (OR = 1.14, 99.9% CI: 0.98-1.33), and G6PD deficiency (OR = 1.85; 99.9%
      CI: 1.11-3.07). Schizophrenia (OR 0.31; 99.9% CI: 0.19-0.50) and smoking (OR
      0.82; 99.9% CI: 0.76-0.89) were significantly less prevalent among pterygium
      patients. CONCLUSIONS: Pterygium etiology is multifactorial. Some demographic,
      systemic, and periocular conditions are significantly more prevalent and some are
      less prevalent among pterygium patients. Better understanding of the
      pathophysiological association between those diseases and pterygium may help in
      its prevention and treatment.

PMID- 25392264
TI  - Causes of Missed Referrals to Low-Vision Rehabilitation Services: Causes in a
      Tertiary Eye Care Setting.
AB  - PURPOSE: To identify the referral pattern and identify causes of missed referrals
      to low-vision services in a tertiary eye care center. METHODS: A retrospective
      review of all the hospital records of patients seen from September-December 2012
      was done to identify patients with visual impairment. Low vision was defined as
      has a best-corrected visual acuity (BCVA) in the better eye of <20/60 to light
      perception (as per WHO definition); or a visual field of <20 degrees  from the
      point of fixation. The frequency of referrals in this database was used to
      identify referral patterns of physicians and also causes for missed referrals for
      these patients. RESULTS: Of 14,938 hospital medical records reviewed during the
      period, 499 patients missed low-vision services with a mean age of 46 +/- 18.2
      years, including 158 females. Among those missed, 12.07% were in the age group 0
      15 years, while 30.9% of the patients were >60 years, with 157 requiring
      rehabilitative services and training. Causes for missed referrals were clear
      misses or non-referrals by the physician (39%), non-acceptance of services by the
      patient (53%), loss from appointment desks (4.5%), and loss to follow-up (3.5%).
      CONCLUSION: Missed referral to low-vision services in tertiary centers can be
      considerable; these need to be identified for optimal utilization and delivery of
      these services to patients with low vision.

PMID- 25392265
TI  - Detecting Optic Atrophy in Multiple Sclerosis Patients Using New Colorimetric
      Analysis Software: From Idea to Application.
AB  - Neuro-ophthalmologists typically observe a temporal pallor of the optic disc in
      patients with multiple sclerosis. Here, we describe the emergence of an idea to
      quantify these optic disc color changes in multiple sclerosis patients. We
      recruited 12 multiple sclerosis patients with previous optic neuritis attack and
      obtained photographs of their optic discs. The Laguna ONhE, a new colorimetric
      software using hemoglobin as the reference pigment in the papilla, was used for
      the analysis. The papilla of these multiple sclerosis patients showed greater
      pallor, especially in the temporal sector. The software detected the pallor and
      assigned hemoglobin percentages below normal reference values. Measurements of
      optic disc hemoglobin levels obtained with the Laguna ONhE software program had
      good ability to detect optic atrophy and, consequently, axonal loss in multiple
      sclerosis patients. This new technology is easy to implement in routine clinical
      practice. 

PMID- 25392266
TI  - Gut commensal microvesicles reproduce parent bacterial signals to host immune and
      enteric nervous systems.
AB  - Ingestion of a commensal bacteria, Lactobacillus rhamnosus JB-1, has potent
      immunoregulatory effects, and changes nerve-dependent colon migrating motor
      complexes (MMCs), enteric nerve function, and behavior. How these alterations
      occur is unknown. JB-1 microvesicles (MVs) are enriched for heat shock protein
      components such as chaperonin 60 heat-shock protein isolated from Escherichia
      coli (GroEL) and reproduce regulatory and neuronal effects in vitro and in vivo.
      Ingested labeled MVs were detected in murine Peyer's patch (PP) dendritic cells
      (DCs) within 18 h. After 3 d, PP and mesenteric lymph node DCs assumed a
      regulatory phenotype and increased functional regulatory CD4(+)25(+)Foxp3+ T
      cells. JB-1, MVs, and GroEL similarly induced phenotypic change in cocultured DCs
      via multiple pathways including C-type lectin receptors specific intercellular
      adhesion molecule-3 grabbing non-integrin-related 1 and Dectin-1, as well as TLR
      2 and -9. JB-1 and MVs also decreased the amplitude of neuronally dependent MMCs
      in an ex vivo model of peristalsis. Gut epithelial, but not direct neuronal
      application of, MVs, replicated functional effects of JB-1 on in situ patch
      clamped enteric neurons. GroEL and anti-TLR-2 were without effect in this system,
      suggesting the importance of epithelium neuron signaling and discrimination
      between pathways for bacteria-neuron and -immune communication. Together these
      results offer a mechanistic explanation of how Gram-positive commensals and
      probiotics may influence the host's immune and nervous systems.

PMID- 25392267
TI  - Nanosecond laser therapy reverses pathologic and molecular changes in age-related
      macular degeneration without retinal damage.
AB  - Age-related macular degeneration (AMD) is a leading cause of vision loss,
      characterized by drusen deposits and thickened Bruch's membrane (BM). This study
      details the capacity of nanosecond laser treatment to reduce drusen and thin BM
      while maintaining retinal structure. Fifty patients with AMD had a single
      nanosecond laser treatment session and after 2 yr, change in drusen area was
      compared with an untreated cohort of patients. The retinal effect of the laser
      was determined in human and mouse eyes using immunohistochemistry and compared
      with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser
      treatment was quantified using electron microscopy and quantitative PCR. In
      patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr.
      Retinal structure was not compromised in human and mouse retina after laser
      treatment, with only a discrete retinal pigment epithelium (RPE) injury, and
      limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse
      3 mo after treatment (ApoEnull treated 683 +/- 38 nm, ApoEnull untreated 890 +/-
      60 nm, C57Bl6J 606 +/- 43 nm), with the expression of matrix metalloproteinase-2
      and -3 increased (>260%). Nanosecond laser resolved drusen independent of retinal
      damage and improved BM structure, suggesting this treatment has the potential to
      reduce AMD progression.

PMID- 25392268
TI  - Macrophage polarization phenotype regulates adiponectin receptor expression and
      adiponectin anti-inflammatory response.
AB  - Adiponectin (APN), a pleiotropic adipokine that exerts anti-inflammatory,
      antidiabetic, and antiatherogenic effects through its receptors (AdipoRs),
      AdipoR1 and AdipoR2, is an important therapeutic target. Factors regulating
      AdipoR expression in monocyte/macrophages are poorly understood, and the
      significance of polarized macrophage activation in controlling AdipoR expression
      and the APN-mediated inflammatory response has not been investigated. The aim of
      this study was to investigate whether the macrophage polarization phenotype
      controls the AdipoR expression and APN-mediated inflammatory response. With the
      use of mouse bone marrow and peritoneal macrophages, we demonstrate that
      classical activation (M1) of macrophages suppressed (40-60% of control) AdipoR
      expression, whereas alternative activation (M2) preserved it. Remarkably, the
      macrophage polarization phenotypes produced contrasting inflammatory responses to
      APN (EC50 5 ug/ml). In M1 macrophages, APN induced proinflammatory cytokines, TNF
      alpha, IL-6, and IL-12 (>10-fold of control) and AdipoR levels. In contrast, in
      M2 macrophages, APN induced the anti-inflammatory cytokine IL-10 without altering
      AdipoR expression. Furthermore, M1 macrophages adapt to a cytokine environment by
      reversing AdipoR expression. APN induced AdipoR mRNA and protein expression by up
      regulating liver X receptor-alpha (LXRalpha) in macrophages. These results
      provide the first evidence that macrophage polarization is a key determinant
      regulating AdipoR expression and differential APN-mediated macrophage
      inflammatory responses, which can profoundly influence their pathogenic role in
      inflammatory and metabolic disorders.

PMID- 25392269
TI  - Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes
      and dermal fibroblasts.
AB  - Peripheral intracrine sex steroid synthesis from adrenal precursors
      dehydroepiandrosterone (DHEA) and DHEA-sulfate has evolved in humans. We sought
      to establish if there are differences in intracrine, paracrine, and endocrine
      regulation of sex steroids by primary cultures of human skin epidermal
      keratinocytes and dermal fibroblasts. Microarray analysis identified
      multifunctional genes modulated by steroids, quantitative RT-PCR (qRT-PCR) mRNA
      expression, enzymatic assay aromatase activity, scratch assay cell migration,
      immunocytochemistry alpha-smooth muscle actin (alpha-SMA), and collagen gel
      fibroblast contraction. All steroidogenic components were present, although only
      keratinocytes expressed the organic anion organic anion transporter protein
      (OATP) 2B1 transporter. Both expressed the G-protein-coupled estrogen receptor
      (GPER1). Steroids modulated multifunctional genes, up-regulating genes important
      in repair and aging [angiopoietin-like 4 (ANGPTL4), chemokine (C-X-C motif)
      ligand 1 (CXCL1), lamin B1 (LMNB1), and thioredoxin interacting protein (TXNIP)].
      DHEA-sulfate (DHEA-S), DHEA, and 17beta-estradiol stimulated keratinocyte and
      fibroblast migration at early (4 h) and late (24-48 h) time points, suggesting
      involvement of genomic and nongenomic signaling. Migration was blocked by
      aromatase and steroid sulfatase (STS) inhibitors confirming intracrine synthesis
      to estrogen. Testosterone had little effect, implying it is not an intermediate.
      Steroids stimulated fibroblast contraction but not alpha-SMA expression.
      Mechanical wounding reduced fibroblast aromatase activity but increased
      keratinocyte activity, amplifying the bioavailability of intracellular estrogen.
      Cultured fibroblasts and keratinocytes provide a biologically relevant model
      system to investigate the complex pathways of sex steroid intracrinology in human
      skin.

PMID- 25392270
TI  - Cellular origins of cold-induced brown adipocytes in adult mice.
AB  - This work investigated how cold stress induces the appearance of brown adipocytes
      (BAs) in brown and white adipose tissues (WATs) of adult mice. In interscapular
      brown adipose tissue (iBAT), cold exposure increased proliferation of endothelial
      cells and interstitial cells expressing platelet-derived growth factor receptor,
      alpha polypeptide (PDGFRalpha) by 3- to 4-fold. Surprisingly, brown adipogenesis
      and angiogenesis were largely restricted to the dorsal edge of iBAT. Although
      cold stress did not increase proliferation in inguinal white adipose tissue
      (ingWAT), the percentage of BAs, defined as multilocular adipocytes that express
      uncoupling protein 1, rose from undetectable to 30% of total adipocytes. To trace
      the origins of cold-induced BAs, we genetically tagged PDGFRalpha(+) cells and
      adipocytes prior to cold exposure, using Pdgfra-Cre recombinase estrogen receptor
      T2 fusion protein (CreER(T2)) and adiponectin-CreER(T2), respectively. In iBAT,
      cold stress triggered the proliferation and differentiation of PDGFRalpha(+)
      cells into BAs. In contrast, all newly observed BAs in ingWAT (5207 out of 5207)
      were derived from unilocular adipocytes tagged by adiponectin-CreER(T2)-mediated
      recombination. Surgical denervation of iBAT reduced cold-induced brown
      adipogenesis by >85%, whereas infusion of norepinephrine (NE) mimicked the
      effects of cold in warm-adapted mice. NE-induced de novo brown adipogenesis in
      iBAT was eliminated in mice lacking beta1-adrenergic receptors. These
      observations identify a novel tissue niche for brown adipogenesis in iBAT and
      further define depot-specific mechanisms of BA recruitment.

PMID- 25392272
TI  - Biological properties of a duck enteritis virus attenuated via serial passaging
      in chick embryo fibroblasts.
AB  - To gain a better understanding of the genetic changes required for attenuation of
      duck enteritis virus (DEV), the Chinese standard challenge strain of DEV (DEV
      CSC) was serially passaged 80 times in chick embryo fibroblasts. We plaque
      purified the virus after the 25th passage (DEV p25) and the 80th passage (DEV
      p80) and investigated its in vitro and in vivo properties. Average plaque sizes
      for DEV p25 and p80 were significantly smaller than those for their parental DEV
      CSC. The results from an in vivo experiment revealed that DEV p25 and p80 were
      avirulent in ducks and protected them from virulent DEV challenge. The complete
      genome sequence of DEV p80 was determined and compared with that of the parent
      virus. An 1801-bp deletion was identified in the genome of DEV p80, which
      affected the genes encoding gI and gE. Moreover, there were 11 base
      substitutions, which led to seven amino acid changes in open reading frames
      LORF9, UL51, UL9, UL7, UL4, ICP4 and US3. Further DNA sequence analysis showed
      that the 1801-bp deletion was also present in DEV p25. Our findings suggest that
      DEV gE and/or gI are nonessential for virus growth and might, as with other
      herpesviruses, play an important role in cell-to-cell spread and virulence. Our
      experiments provide more genetic information about DEV attenuation and further
      advance our understanding of the molecular basis of DEV pathogenesis. 

PMID- 25392271
TI  - Hematopoietic Akt2 deficiency attenuates the progression of atherosclerosis.
AB  - Atherosclerosis is the major cause of death and disability in diabetic and obese
      subjects with insulin resistance. Akt2, a phosphoinositide-dependent serine
      threonine protein kinase, is highly express in insulin-responsive tissues;
      however, its role during the progression of atherosclerosis remains unknown.
      Thus, we aimed to investigate the contribution of Akt2 during the progression of
      atherosclerosis. We found that germ-line Akt2-deficient mice develop similar
      atherosclerotic plaques as wild-type mice despite higher plasma lipids and
      glucose levels. It is noteworthy that transplantation of bone marrow cells
      isolated from Akt2(-/-) mice to Ldlr(-/-) mice results in marked reduction of the
      progression of atherosclerosis compared with Ldlr(-/-) mice transplanted with
      wild-type bone marrow cells. In vitro studies indicate that Akt2 is required for
      macrophage migration in response to proatherogenic cytokines (monocyte
      chemotactic protein-1 and macrophage colony-stimulating factor). Moreover, Akt2(
      /-) macrophages accumulate less cholesterol and have an alternative activated or
      M2-type phenotype when stimulated with proinflammatory cytokines. Together, these
      results provide evidence that macrophage Akt2 regulates migration, the
      inflammatory response and cholesterol metabolism and suggest that targeting Akt2
      in macrophages might be beneficial for treating atherosclerosis.

PMID- 25392273
TI  - Diagnostic criteria for IgG4-related ophthalmic disease.
AB  - Immunoglobulin G4 (IgG4)-related disease is a novel clinical entity characterized
      by infiltration of IgG4-immunopositive plasmacytes and elevated serum IgG4
      concentration accompanied by enlargement of and masses in various organs,
      including the lacrimal gland, salivary gland, and pancreas. Recent studies have
      clarified that conditions previously diagnosed as Mikulicz disease as well as
      various types of lymphoplasmacytic infiltrative disorders of the ocular adnexa
      are consistent with a diagnosis of IgG4-related disease. Against this background,
      the diagnostic criteria for IgG4-related ophthalmic disease have recently been
      established, based on both the clinical and the histopathologic features of the
      ocular lesions. This article reviews these new criteria with reference to the
      comprehensive diagnostic criteria for IgG4-related disease for all systemic
      conditions reported in 2012. 

PMID- 25392274
TI  - Comparative efficacy of pure yellow (577-nm) and 810-nm subthreshold micropulse
      laser photocoagulation combined with yellow (561-577-nm) direct photocoagulation
      for diabetic macular edema.
AB  - PURPOSE: To compare the efficacy of 577- and 810-nm subthreshold micropulse laser
      photocoagulation (SMLP) combined with direct photocoagulation to microaneurysms
      in diabetic macular edema (DME). METHODS: A prospective nonrandomized
      interventional case series. Forty-nine consecutive patients (53 eyes) with DME
      were recruited. In 20/24 (83.3%) eyes, 810-nm SMLP (810-nm MP) to achieve a
      confluent grid pattern was followed by direct photocoagulation to microaneurysms
      via a continuous 561-nm wavelength laser. In 21/29 (72.5%) eyes, 577-nm SMLP (577
      nm MP) was combined with direct photocoagulation to microaneurysms via the same
      instrument. Best-corrected visual acuity (BCVA) and central macular thickness
      (CMT) were examined 1, 2, 3, 6 and 12 months after treatment. RESULTS: The mean
      power required for SMLP was lower in the 577-nm than in the 810-nm MP group
      (204.1 vs. 954.1 mW) (p < 0.0001). Significant reductions in CMT persisted from 3
      to 12 months after treatment in all patients (p < 0.01). There were no
      significant intergroup differences in CMT until 12 months. In both groups, mean
      BCVA remained stable until 12 months after treatment. Additional treatment for
      persistent macular edema was performed within 12 months in 4/24 eyes (16.7%) in
      the 810-nm MP group and 1/29 eyes (3.4%) in the 577-nm MP group. CONCLUSION:
      Either 577-nm MP or 810-nm MP combined with direct photocoagulation for
      microaneurysm closure reduced DME, maintained visual acuity and reduced the
      additional treatment rate within 12 months. The 577-nm MP apparatus required less
      energy for SMLP than the 810-nm MP instrument and was suitable for direct
      photocoagulation of microaneurysms.

PMID- 25392275
TI  - [Chronic lymphocytic leukemia: current standards and novel approaches].
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western
      world and affects mainly elderly patients. In current phase III trials, standard
      treatment options were established that differ mainly based on the fitness and
      age of the patient. The combination of fludarabine, cyclophosphamide, and the
      CD20 antibody rituximab (FCR) is recommended for young patients without relevant
      comorbidity, while bendamustine and rituximab (BR) should be favored for elderly
      (ca. >65 years) fit individuals. Bendamustine plus ofatumumab is another option
      in this situation. Patients with major comorbidities should receive chlorambucil
      combined with CD20 antibody (obinutuzumab or ofatumumab). In 2014, several new
      compounds were approved for patients with ultrahigh risk genetic factors (17p-,
      TP53mut) and for relapsed/refractory CLL: both idelalisib and ibrutinib are
      orally bioavailable kinase inhibitors that block key regulators of central
      pathways. For both agents, very impressive data are available with regard to
      tolerability and efficacy that will change the treatment paradigm in CLL. With
      ABT-199, a direct apoptosis inducer is being developed that in early clinical
      trials produced high remission rates combined with good tolerability.
      Combinations and sequences of the "novel" compounds obinutuzumab, ofatumumab,
      idelalisib, ibrutinib, and ABT-199 will be studied in coming years in clinical
      trials in order to prolong remission duration and reduce side effects with the
      eventual aim of curing CLL.

PMID- 25392277
TI  - Dose-dependent effects of perinatal hypothyroidism on postnatal testicular
      development in rat offspring.
AB  - The role of thyroid hormones in gonad development remains incompletely
      understood. We examined the dose-related effects of perinatal hypothyroidism
      induced by a reversible goitrogen, 6-propyl-2-thiouracil (PTU), on reproductive
      development in male rat offspring. Timed-pregnant Sprague-Dawley rats were orally
      administered PTU (0, 0.5, 1.0, or 2.0 mg/kg/day) by gavage from gestational day
      15 through postnatal day 20. We observed a significant dose-dependent decrease in
      body weight in offspring with PTU exposure up to 13 weeks of age, but body weight
      became comparable among groups by 26 weeks of age. Testicular weight tended to be
      lower up to 7 weeks but was higher after 13 weeks of age. Epididymis weight was
      not different among the groups at any age. Plasma concentrations of thyroxine and
      triiodothyronine in the PTU groups were significantly lower at 3 weeks of age but
      recovered to normal levels by 26 weeks of age. No dose-related trend in plasma
      testosterone concentrations was found. Seminiferous tubules were larger at 13 and
      26 weeks of age with PTU exposure. The number of Sertoli cells was significantly
      higher from 3 through 26 weeks of age. The number of Leydig cells was
      significantly lower up to 7 weeks of age but was comparable among groups from 13
      weeks of age onwards. Thus, transient gestational and lactational thyroid hormone
      suppression induced small testes in early life but led to paradoxical dose
      dependent testicular enlargement in adults as indicated partly by larger
      seminiferous tubules with numerous Sertoli cells in male rat offspring. 

PMID- 25392276
TI  - Comparison of demographics, treatment patterns, health care utilization, and
      costs among elderly patients with extensive-stage small cell and metastatic non
      small cell lung cancers.
AB  - BACKGROUND: Limited data exist regarding real-world treatment patterns, resource
      utilization, and costs of extensive-stage small cell lung cancer (esSCLC) among
      elderly patients in the United States. While abundant data are available on
      treatment patterns in metastatic non-small cell lung cancer (mNSCLC), to our
      knowledge no data exist comparing costs and resource use between patients with
      esSCLC or mNSCLC. METHODS: We retrospectively analyzed administrative claims data
      (2000-2008) of patients aged >=65 years from the linked Surveillance,
      Epidemiology and End Results (SEER)-Medicare database. Patients were selected on
      the basis of having newly diagnosed esSCLC (n=5,855) or mNSCLC (n=24,090) during
      1/1/2000-12/31/2005, and were required to have received cancer-directed therapy.
      Survival and other measures were compared between esSCLC and mNSCLC patients
      using Kaplan-Meier log-rank and univariate chi-square and t-tests. Study measures
      were followed from first diagnosis date of either esSCLC or mNSCLC until the
      earlier of death or end of the database. RESULTS: Survival between the cohorts
      did not differ significantly: mean of 10.4 months for esSCLC patients versus 11.1
      months for mNSCLC; median survival was 7.4 months versus 5.9 months. A higher
      percentage of mNSCLC patients (vs. esSCLC) received radiation therapy (75.6% vs.
      65.4%; P < 0.001) and surgery (13.6% vs. 7.8%; P < 0.001) during the metastatic
      disease period. Conversely, a higher percentage of esSCLC patients than mNSCLC
      patients received chemotherapy (85.5% vs. 60.3%; P < 0.001), red blood-cell
      transfusion (20.7% vs. 10.9%; P < 0.001), platelet transfusion (5.6% vs. 1.8%; P
      < 0.001), and growth-factor support (59.0% vs. 39.5%; P < 0.001). esSCLC patients
      incurred higher lifetime disease-related costs ($44,167 vs. $37,932; P < 0.001)
      and all-cause costs ($70,549 vs. $67,176; P < 0.001) than mNSCLC patients.
      CONCLUSIONS: Lifetime total and disease-related costs per patient were high.
      Increased use of chemotherapy, supportive care therapies (including growth
      factors), and disease-related hospitalizations were observed in esSCLC patients
      as compared with mNSCLC patients. Disease-related and all-cause costs for esSCLC
      also exceeded those of mNSCLC, except for hospice and skilled nursing services.
      Survival and per-patient costs for both groups underscore the unmet medical need
      for more effective therapies in patients with esSCLC or mNSCLC.

PMID- 25392278
TI  - Role of tumor necrosis factor-alpha and interleukin-1beta in anorexia induction
      following oral exposure to the trichothecene deoxynivalenol (vomitoxin) in the
      mouse.
AB  - The trichothecene deoxynivalenol (DON), a foodborne mycotoxin found in grain
      based foods, has been associated with human and animal food poisoning. Although
      induction of anorexia has been described as a hallmark of DON-induced toxicity in
      many animal species, the mechanistic basis for this adverse effect is not fully
      understood. The purpose of this research was to determine the role of two
      proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) in DON-induced anorexia. In a nocturnal mouse food
      consumption model, DON-induced anorectic response occurred at 1 hr and lasted up
      to 6 hr. Similar anorectic effects were observed following acute administration
      of exogenous TNF-alpha and IL-1beta. Oral exposure to DON at 5 mg/kg bw
      stimulated splenic and hepatic mRNA and plasma protein elevations of TNF-alpha
      and IL-1beta that corresponded to anorexia induction. Pretreatment with the TNF
      alpha receptor (TNFR) antagonist R-7050 dose-dependently attenuated both TNF
      alpha- and DON-induced anorexia. While, the type 1 IL-1 receptor (IL-1R1)
      antagonist IL-1RA dose-dependently attenuated both IL-1beta- and DON-induced
      anorexia. Taken together, the results suggest that both TNF-alpha and IL-1beta
      play contributory role in anorexia induction following oral exposure to DON. 

PMID- 25392279
TI  - The midpoint of sleep on working days: a measure for chronodisruption and its
      association to individuals' well-being.
AB  - There is consistent evidence suggesting a relationship between individuals' sleep
      wake rhythms and well-being. The indiscriminate demands from daily working
      routines, which do not respect this individual physiological rhythm, might be
      mediating this phenomenon. The aim of the present study was to evaluate the
      relationship between the characteristics of sleep routines during working days
      and psychological well-being. This was a cross-sectional study on 825 individuals
      from rural communities from southern Brazil. The study protocol included a
      questionnaire on demographic characteristics, working routines, health
      complaints, and habits; the Munich Chronotype Questionnaire for sleep-wake rhythm
      and; the WHO-Five well-being index. Since sex has been shown to affect sleep
      circadian rhythm and well-being, analysis was performed on men and women
      separately. In the proposed hierarchical regression models, different factors
      contributed to well-being according to sex. Among men, sleep-wake and work
      related variables did not predict well-being scores. Among women, later midpoints
      of sleep on working days (B = -1.243, SE B = 0.315, beta = -0.220), working more
      days per week (B = -1.507, SE B = 0.494, beta = 0.150), having longer working
      journeys (B = -0.293, SE B = 0.105, beta = -0.166), earlier working journey
      midpoints (B = 0.465, SE B = 0.222, beta = 0.115), and being exposed to less
      sunlight (B = 0.140, SE B = 0.064, beta = 0.103) predicted worse well-being. For
      the subgroup of women with days free from work, we have found a correlation
      between later midpoints of sleep during the week with worse well-being (Pearson's
      r = -0.159, p = 0.045) while the same relationship was not significantly observed
      with the midpoint of sleep on non-working days (Pearson's r = -0.153, p = 0.054).
      Considering WHO-Five as categorical, based on proposed clinical cut-offs, among
      women working 7-d/week, those with worst well-being (WHO-Five < 13) had the
      latest midpoint of sleep (F = 4.514, p = 0.012). Thus, the midpoint of sleep on
      working days represents the interaction between individuals' sleep-wake behavior
      and working routines. It plays an important role as a stress factor and may be a
      useful alternative variable related to chronodisruption. 

PMID- 25392280
TI  - Effects of long-term microgravity exposure in space on circadian rhythms of heart
      rate variability.
AB  - We evaluated their circadian rhythms using data from electrocardiographic records
      and examined the change in circadian period related to normal RR intervals for
      astronauts who completed a long-term (>=6-month) mission in space. The examinees
      were seven astronauts, five men and two women, from 2009 to 2010. Their mean +/-
      SD age was 52.0 +/- 4.2 years (47-59 yr). Each stayed in space for more than 160
      days; their average length of stay was 172.6 +/- 14.6 days (163-199 days). We
      conducted a 24-h Holter electrocardiography before launch (Pre), at one month
      after launch (DF1), at two months after launch (DF2), at two weeks before return
      (DF3), and at three months after landing (Post), comparing each index of
      frequency-domain analysis and 24-h biological rhythms of the NN intervals (normal
      RR intervals). Results show that the mean period of Normal Sinus (NN) intervals
      was within 24 +/- 4 h at each examination. Inter-individual variability differed
      among the stages, being significantly smaller at DF3 (Pre versus DF1 versus DF3
      versus Post = 22.36 +/- 2.50 versus 25.46 +/- 4.37 versus 22.46 +/- 1.75 versus
      26.16 +/- 7.18 h, p < 0.0001). The HF component increased in 2 of 7 astronauts,
      whereas it decreased in 3 of 7 astronauts and 1 was remained almost unchanged at
      DF1. During DF3, about 6 months after their stay in space, the HF component of 5
      of 7 astronauts recovered from the decrease after launch, with prominent
      improvement to over 20% in 3 astronauts. Although autonomic nervous functions and
      circadian rhythms were disturbed until one month had passed in space, well
      scheduled sleep and wake rhythms and meal times served as synchronizers. 

PMID- 25392281
TI  - The influence of chronotype and intelligence on academic achievement in primary
      school is mediated by conscientiousness, midpoint of sleep and motivation.
AB  - Individuals differ in their timing of sleep (bed times, rise times) and in their
      preference for morning or evening hours. Previous work focused on the
      relationship between academic achievement and these variables in secondary school
      students. The main aim of the study is to investigate the relationship between
      chronotype and academic achievement in 10-year-old children (n = 1125) attending
      4th grade of primary school. They filled a cognitive test (Culture Fair
      Intelligence Test, CFT 20-R) and questions about rise times and bed times,
      academic achievement, conscientiousness and motivation. We used the "scales for
      the assessment of learning and performance motivation" (SELLMO; Skalen zur
      Erfassung der Lern- und Leistungsmotivation for motivation), the short version of
      the Five-Factor Personality Inventory Children (FFPI-C) to measure
      conscientiousness, and the Composite Scale of Morningness (CSM) to assess
      morningness-eveningness. Mean CSM score was 37.84 +/- 6.66, midpoint of sleep was
      1:36 +/- 00:25 and average sleep duration (time in bed) was 10:15 +/- 0:48.
      Morningness orientation was positively related to intelligence, conscientiousness
      and learning objectives. Eveningness orientation was related to avoidance
      performance objectives and work avoidance. Early midpoint of sleep,
      conscientiousness and intelligence were associated with better grades. The
      multivariate model showed that intelligence was the strongest predictor of good
      grades. Conscientiousness, motivation, younger age and an earlier midpoint of
      sleep were positively related to good grades. This is the first study in primary
      school pupils, and it shows that the relationship between evening orientation and
      academic achievement is already prevalent at this age even when controlling for
      important predictors of achievement. 

PMID- 25392282
TI  - Solvent-assisted optimal BaTiO3 nanoparticles-polymer composite cluster formation
      for high performance piezoelectric nanogenerators.
AB  - We report on an optimal BaTiO3-P(VDF-HFP) composite thin-film formation process
      for high performance piezoelectric nanogenerators (NGs). By examining different
      solvent ratios in a solvent-assisted composite thin film formation process, the
      BTO nanoparticle (NPs) clustering and related performance enhancements were
      carefully investigated. Using the optimal process, the fabricated BTO NGs
      exhibited an excelling output power performance. Under a compressive force of
      ~0.23 MPa normal to the surface, the measured open-circuit output voltage and
      short-circuit current were over 110 V and 22 MUA, respectively, with a
      corresponding peak output power density of 0.48 Wcm(-3). Our results clearly
      demonstrate the effectiveness of a solvent-assisted BTO cluster formation process
      for fabricating high performance piezoelectric energy harvesting devices. 

PMID- 25392283
TI  - From the editors.

PMID- 25392284
TI  - Contingency management for patients with dual disorders in intensive outpatient
      treatment for addiction.
AB  - OBJECTIVE: This quality improvement program evaluation investigated the
      effectiveness of contingency management for improving retention in treatment and
      positive outcomes among patients with dual disorders in intensive outpatient
      treatment for addiction. METHODS: The effect of contingency management was
      explored among a group of 160 patients exposed to contingency management (n = 88)
      and not exposed to contingency management (no contingency management, n = 72) in
      a six-week partial hospitalization program. Patients referred to the partial
      hospitalization program for treatment of substance use and comorbid psychiatric
      disorders received diagnoses from psychiatrists and specialist clinicians
      according to the Diagnostic and Statistical Manual of the American Psychiatric
      Association. A unique application of the contingency management "fishbowl" method
      was used to improve the consistency of attendance at treatment sessions, which
      patients attended 5 days a week. Days attending treatment and drug-free days were
      the main outcome variables. Other outcomes of interest were depression, anxiety
      and psychological stress, coping ability, and intensity of drug cravings.
      RESULTS: Patients in the contingency management group attended more treatment
      days compared to patients in the no contingency management group; M = 16.2 days
      (SD = 10.0) versus M = 9.9 days (SD = 8.5), respectively; t = 4.2, df = 158, p
      <.001. No difference was found between the treatment groups on number of drug
      free days. Psychological stress and drug craving were inversely associated with
      drug-free days in bivariate testing (r = -.18, p <.02; r = -.31, p <.001,
      respectively). Treatment days attended and drug craving were associated with drug
      free days in multivariate testing (B =.05, SE =.01, beta =.39, t = 4.9, p <.001;
      B = -.47; SE =.12, beta = -.30, t = -3.9, p <.001, respectively; Adj. R(2) =.21).
      Days attending treatment partially mediated the relationship between exposure to
      contingency management and self-reported drug-free days. CONCLUSIONS: Contingency
      management is a valuable adjunct for increasing retention in treatment among
      patients with dual disorders in partial hospitalization treatment. Exposure to
      contingency management increases retention in treatment, which in turn
      contributes to increased drug-free days. Interventions for coping with
      psychological stress and drug cravings should be emphasized in intensive dual
      diagnosis group therapy.

PMID- 25392286
TI  - Barriers to implementation of treatment guidelines for ADHD in adults with
      substance use disorder.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is common among adult
      patients with a substance use disorder, yet often goes undetected. This is a
      qualitative study to explore implementation barriers to a guideline developed in
      Belgium for the recognition and treatment of ADHD in adult patients with
      substance use disorder and to gain a better understanding of the strategies to
      overcome these barriers. METHODS: Focus groups were conducted with caregivers and
      patients to explore experiences with comorbid substance use disorder and ADHD.
      The barriers reported in these focus groups became the subject of further study
      in focus groups with addiction professionals (physicians, psychiatrists, and
      psychologists) who had tried the guideline and with psychiatrists specializing in
      addiction but without experience with ADHD. RESULTS: Our analysis revealed a
      number of barriers to the implementation of this guideline, including lack of
      information from the family, pressure from patients and caregivers to make an
      ADHD diagnosis, and the potential for abuse of ADHD medication. Furthermore,
      diagnostic instruments for ADHD have not been validated in people with substance
      use disorder. Although patients with ADHD are usually treated in an outpatient
      setting, patients with ADHD comorbid with substance use disorder are difficult to
      identify in an outpatient setting for various reasons. Finally, there is a lack
      of specific ADHD expertise in substance use treatment organizations. CONCLUSIONS:
      Despite the availability of an approved guideline for recognizing and treating
      adult ADHD in patients with a substance use disorder, underdiagnosis and
      inadequate treatment still persist. As in general substance use treatment,
      medication only plays a supportive role in the treatment of substance use
      disorder with comorbid ADHD. An integrated approach and further improvements in
      the competence of practitioners may help to reduce the resistance to diagnosing
      ADHD in substance use treatment centers. Practitioners who specialize in
      addiction medicine and therapists without medical education view the problem from
      different perspectives and therefore each group needs specific information and
      training. Targeted interventions need to be developed to keep these patients in
      treatment.

PMID- 25392285
TI  - Relationships between drinking motives and smoking expectancies among daily
      smokers who are also problem drinkers.
AB  - OBJECTIVE: There is a high co-occurrence of problem drinking and regular
      cigarette smoking, and cognitive processes (e.g., motivation to use, expectations
      about the consequences of use) related to each are positively associated with one
      another. We explored drinking motives in relation to cognitive-based smoking
      processes among smokers with problematic drinking. We expected that drinking
      coping motives would be associated with smoking consequences related to negative
      reinforcement and negative personal outcomes and inflexibility of smoking
      behavior; observed effects for coping motives would be unique from shared
      variance with other motives and incrementally evident beyond the variance
      accounted for by tobacco-related health problems, smoking rate, negative
      affectivity, cannabis use, and gender. METHODS: The sample included 195
      individuals recruited into a larger study of smoking cessation treatments (i.e.,
      they were interested in quitting), who were heavy drinkers and smoked daily.
      Participants were primarily male (n = 122, 63%), fairly young (Mage = 30.3 years;
      SD = 12.46), and predominantly White/Caucasian (n = 175, 80%). Roughly 57% (n =
      111) had at least one comorbid Axis I disorder, the most common being social
      anxiety (n = 21, 11%) and generalized anxiety disorder (n = 12, 6%). RESULTS:
      Coping drinking motives predicted negative smoking consequences, negative
      reinforcement, and smoking inflexibility. Enhancement drinking motives marginally
      predicted positive reinforcement. Conformity drinking motives predicted smoking
      consequences related to appetite/weight control. Social drinking motives
      predicted negative reinforcement and barriers to cessation and marginally
      predicted positive reinforcement. CONCLUSIONS: Theoretical models and clinical
      activities focused on smoking cessation among problem drinkers may benefit from
      considering the role of drinking motives, particularly coping-oriented motives,
      to better understanding cognitive-based smoking processes.

PMID- 25392287
TI  - Dual diagnosis discourse in Victoria Australia: the responsiveness of mental
      health services.
AB  - OBJECTIVE: In recent decades, psychiatric services have been challenged to be
      more responsive to patients' coexisting problems, in particular those concerning
      substance use. In Australia this has been referred to as a "No Wrong Door"
      approach. This paper explores the meanings of this move for the acute mental
      health sector, including attitudes toward a No Wrong Door approach to people with
      a dual diagnosis of mental illness and substance use disorder.   METHODS: This
      qualitative study involved a review of the research literatures, analysis of
      policy documents, and interviews with 19 key informants in a case study of the
      State of Victoria, Australia.   RESULTS: The analysis resulted in two broad
      themes surrounding the implications of dual diagnosis discourse for the mental
      health sector. The first involves progress regarding the concept of No Wrong Door
      with subthemes including interprofessional cultural conflicts, intersectoral
      professional status issues, terminology, problem definition, perspectives on
      serious mental illness, the role of the client, and pharmacological treatment.
      The second overarching theme focuses upon informants' thoughts on future
      directions for the sector and highlights divided opinion on the implications of
      dual diagnosis discourse for the mental health service and social care systems.  
      CONCLUSIONS: While the perspectives on system change and multiple issues such as
      resource concerns and cultural clashes are presented here, the informants in this
      study also gave clear guidance for the future of dual diagnosis work in the
      mental health sector (e.g., focusing on orienting services toward consumer
      strengths and recovery), along with recommendations for future research. This
      paper contributes to the small body of qualitative research on the history and
      course of efforts to develop appropriate practice in mental health services with
      regard to patients who have substance use problems and other mental health
      disorders.

PMID- 25392288
TI  - Guest editorial: epidemiological studies.

PMID- 25392289
TI  - Dual diagnosis among physicians: a clinical perspective.
AB  - Co-occurrence of mental disorders and substance use disorders (dual diagnosis)
      among doctors is a cause of serious concern due to its negative personal,
      professional, and social consequences. This work provides an overview of the
      prevalence of dual diagnosis among physicians, suggests a clinical etiological
      model to explain the development of dual diagnosis in doctors, and recommends
      some treatment strategies specifically for doctors. The most common presentation
      of dual diagnosis among doctors is the combination of alcohol use disorders and
      affective disorders. There are also high rates of self-medication with
      benzodiazepines, legal opiates, and amphetamines compared to the general
      population, and cannabis use disorders are increasing, mainly in young doctors.
      The prevalence of nicotine dependence varies from one country to another
      depending on the nature of public health policies. Emergency medicine physicians,
      psychiatrists, and anaesthesiologists are at higher risk for developing a
      substance use disorder compared with other doctors, perhaps because of their
      knowledge of and access to certain legal drugs. Two main pathways may lead
      doctors toward dual diagnosis: (a) the use of substances (often alcohol or self
      prescribed drugs) as an unhealthy strategy to cope with their emotional or mental
      distress and (b) the use of substances for recreational or other purposes. In
      both cases, doctors tend to delay seeking help once a problem has been
      established, often for many years. Denial, minimization, and rationalization are
      common defense mechanisms, maybe because of the social stigma associated with
      mental or substance use disorders, the risk of losing employment/medical license,
      and a professional culture of perfectionism and denial of emotional needs or
      failures. Personal vulnerability interacts with these factors to increase the
      risk of a dual diagnosis developing in some individuals. When doctors with
      substance use disorders accept treatment in programs specifically designed for
      them (Physicians' Health Programs), they show better outcomes than the general
      population. However, physicians with dual diagnosis have more psychological
      distress and worse clinical prognosis than those with substance use disorders
      only. Future studies should contribute to a better comprehension of the risk and
      protective factors and the evidence-based treatment strategies for doctors with
      dual diagnosis. 

PMID- 25392290
TI  - Inpatient physicians and nurses with dual diagnosis: an exploratory study.
AB  - OBJECTIVE: This study explored the clinical features of physicians and nurses
      with dual diagnosis.   METHODS: We conducted a retrospective review of 150
      medical records of physicians (n = 120) and nurses (n = 30) admitted from
      February 2008 to February 2011 to the Barcelona Psychiatric Inpatient Unit for
      Health Professionals. Routine intake included the Spanish version of the
      Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) and
      a clinical interview.   RESULTS: The mean age of participants was 48.59 (SD =
      8.9) years and 57.3% were male. Patients experienced substance dependence with
      alcohol (n = 112, 74.7%), sedatives (n = 59, 39.3%), cocaine (n = 24, 16%), other
      stimulants (n = 15, 10%), and opiates other than heroin (n = 16, 10.7%). About
      41% (n = 61) also met criteria for a mental health disorder, mainly major
      depressive disorder (n = 42, 28%), while 8% (n = 12) had attention deficit
      hyperactivity disorder. A high proportion of physicians (n = 95, 79.2%) and
      nurses (n = 25, 83.3%) had nicotine dependence. The most common comorbidity was
      alcohol dependence and major depressive disorder. No differences were found
      between groups in the prevalence of substance use disorders, mental health
      disorders, and dual diagnosis.   CONCLUSIONS: Dual diagnosis is a common
      condition among inpatient physicians and nurses with substance use disorders and
      its clinical presentation may be similar in both groups.

PMID- 25392291
TI  - Substance use and social anxiety in transsexual individuals.
AB  - OBJECTIVE: This study examined social anxiety and use of cannabis and cocaine
      among transsexuals. METHODS: A total of 379 transsexuals seeking treatment or
      consultation participated in this study, providing data on sociodemographics,
      substance use, and anxiety. Analyses were based on (a) lifetime but not current
      use versus never used and (b) current use only versus no current use (lifetime
      only or never used). RESULTS: Lifetime only cannabis users (n = 72, 19%) and
      lifetime only cocaine users (n = 36, 9.8%) were older, had more victimization,
      and received more mental health treatment that those who never used. Current
      cannabis users (n = 47, 12.4%) had higher scores on fear of negative evaluation
      and social avoidance than those not currently using (p <.01). Multivariate
      analysis showed that social avoidance and fear of negative evaluation were
      associated with current cannabis use (p <.05), but not cocaine. Further, being
      single was associated with current cannabis use, after controlling for social
      avoidance and fear of negative evaluation (p <.05). CONCLUSIONS: Transsexuals'
      levels of anxiety and cannabis/cocaine use are comparable to those in the general
      population. Cannabis may be used to control anxiety and can have detrimental
      clinical implications for transsexuals.

PMID- 25392292
TI  - Use of synthetic cannabinoids in patients with psychotic disorders: case series.
AB  - An increasing number of synthetic cannabinoids have become available on the black
      market in recent years, and health professionals have seen a corresponding
      increase in use of these compounds among patients with psychiatric disorders.
      Unfortunately, there is almost no research available in the literature on this
      topic, and what little exists is based on case reports of individuals without
      psychiatric disorders. Synthetic cannabinoids are functionally similar to, but
      structurally different from, delta-9-tetrahydrocannabinol, the active principle
      in cannabis, and are problematic for many reasons. The psychotropic action of
      synthetic cannabinoids in patients with schizophrenia is unpredictable, with very
      diverse clinical presentations. These drugs can be much more potent than delta-9
      tetrahydrocannabinol, they are readily available and difficult to detect. The
      gold standard for identification of synthetic cannabinoids is gas chromatography
      with mass spectrometry, but even this is difficult because new formulations of
      these designer drugs are constantly emerging. In this manuscript, we provide an
      overview and discussion of synthetic cannabinoids and present four cases of
      patients with synthetic cannabinoid intoxication who were hospitalized in our
      intensive psychiatric unit at the time of intoxication. All patients had a
      history of schizophrenia and had been hospitalized several times previously.
      While hospitalized, they smoked an unknown substance brought in by a visitor,
      which was then confirmed using gas chromatography with mass spectrometry to be
      the synthetic cannabinoid AM-2201. Our patients experienced predominantly
      psychiatric adverse clinical effects. We observed the appearance of new psychotic
      phenomena, without exacerbation of their previously known psychotic symptoms, as
      well as the occurrence or marked worsening of mood and anxiety symptoms. Despite
      several similar reactions, and even though they ingested the same exact
      substance, the clinical picture differed markedly between individual patients. We
      assume that the acute effects of synthetic cannabinoids in patients with
      schizophrenia would be different from those in persons without psychotic
      disorders. The reasons for this difference could be the actual symptomatology of
      the presenting disorder, the impact of psychopharmacotherapy, individual patient
      differences and probably many, as yet unknown, factors. The long-term
      consequences of synthetic cannabinoid use on preexisting psychotic disorders are
      unclear. 

PMID- 25392293
TI  - Toxoplasmosis in dogs: first report of Toxoplasma gondii infection in any animal
      species in Angola.
AB  - Despite the worldwide importance of zoonotic parasite Toxoplasma gondii, nothing
      is known of toxoplasmosis in animals in Angola. The present study aimed at
      estimating the seroprevalence and also at assessing correlates of T. gondii
      infection in pet dogs from Luanda, Angola. Dogs (n = 103) brought to a veterinary
      clinic in the city of Luanda were investigated. Serum samples were tested for
      antibodies to T. gondii with a modified agglutination test (MAT) commercial kit,
      at serial dilutions of 1?20 to 1?160. In accordance with the established cutoff
      value (MAT ?20), 16 dogs [15.5%; 95% confidence interval (CI): 9.2-24.0%] had
      antibodies to T. gondii: 10 had a titer of 20, two had a titer of 40, and four
      had a titer of 80. Age (?12 months) was found to be a risk factor for infection
      [odds ratio (OR) = 9.23; 95% CI: 1.16-73.27). For each 1-year increase in age,
      the risk of a dog being found seropositive significantly increased by an OR of
      1.18 (95% CI: 1.02-1.36). The present study, which represents the first
      serological survey of T. gondii in any animal species from Angola, reveals a
      15.5% seroprevalence of infection in pet dogs in Luanda. Further studies are
      needed to better understand the epidemiology of zoonotic T. gondii infection in
      Luanda and also in Angola.

PMID- 25392294
TI  - Hyperglycemia predicts persistently lower muscle strength with aging.
AB  - OBJECTIVE: Persons with diabetes have accelerated muscle loss compared with their
      counterparts. The relationship of hyperglycemia per se to declines in muscle
      function has not been explored yet has implications for developing appropriate
      intervention strategies to prevent muscle loss. RESEARCH DESIGN AND METHODS: We
      examined 984 participants aged 25-96 years in the Baltimore Longitudinal Study of
      Aging (2003-2011) with HbA1c, knee extensor strength (isokinetic dynamometer),
      and lean body mass (DEXA) measured at baseline. Participants had repeated
      measurements up to 7.5 years later. Muscle quality was defined as knee extensor
      strength/leg lean mass. Participants were categorized by HbA1c quartile (<5.5,
      5.5-5.79, 5.8-6.09, and >=6.1% or <37, 37-40, 40-43, and >=43 mmol/mol). Mixed
      effects regression models were used to examine the regression of muscle outcomes
      on HbA1c. RESULTS: Muscle strength and quality were significantly lower across
      HbA1c quartiles (both P < 0.001), without differences in muscle mass at baseline.
      Comparing highest versus lowest HbA1c quartiles and adjusting for age, race, sex,
      weight, and height, strength was significantly lower (-4.70 +/- 2.30 N . m; P
      value trend = 0.02) and results were unchanged after adjustment for physical
      activity (P value trend = 0.045) but of borderline significance after additional
      adjustment for peripheral neuropathy (P value trend = 0.05). Adjusting for
      demographics, muscle quality was significantly lower (-0.32 +/- 0.15 N . m/kg; P
      value trend = 0.02) in the highest versus lowest HbA1c quartiles, but differences
      were attenuated after adjusting for weight and height (-0.25 +/- 0.15 N . m/kg; P
      value trend = 0.07). Muscle mass measures were similar across HbA1c quartiles.
      CONCLUSIONS: Hyperglycemia is associated with persistently lower muscle strength
      with aging, but this effect may be mediated, at least in part, by peripheral
      neuropathy. Future studies should explore if better glycemic control can preserve
      muscle function in diabetes.

PMID- 25392295
TI  - Resveratrol improves high-fructose-induced vascular dysfunction in rats.
AB  - High levels of fructose in the diet results in metabolic abnormalities and
      vascular disorders. In this study, the effect of resveratrol (RES) on vascular
      relaxation and contraction responses was examined in the aorta of high-fructose
      (HFr)-fed rats. mRNA expressions of aortic sirtuin 1 (SIRT1), GLUT5, and aldolase
      B were also investigated. Rats were given fructose (30%) and (or) RES (50 mg . L(
      1)) in their drinking water for 8 weeks. In the HFr-fed rats, plasma levels of
      arginine and the ratio of arginine:asymmetric dimethylarginine (ADMA) decreased,
      whereas leptin levels increased. Decreased relaxation and increased contractile
      responses were detected in aortic rings. However, the aortic expressions of
      SIRT1, GLUT5, and aldolase B remained unchanged. RES treatment restored HFr
      induced vascular dysfunction without improvements in insulin resistance.
      Treatment of HFr-fed rats with RES increased plasma levels of arginine and the L
      arginine:ADMA ratio, and decreased plasma levels of leptin. RES increased SIRT1
      expression, but decreased the expression of GLUT5 and aldolase B in aortas from
      HFr-fed rats. These results suggest that RES contributes to the restoration of
      HFr-induced vascular dysfunction in rats, at least in part, by up-regulation of
      SIRT 1 and down-regulation of GLUT5 and aldolase B in the aorta. Moreover, RES
      may have a positive influence on vasculature by partly restoring the plasma
      arginine:ADMA ratio and leptin levels.

PMID- 25392296
TI  - Interpretation of early life mortality rates.

PMID- 25392297
TI  - Type 2 diabetes self-management education programs in high and low mortality
      developing countries: a systematic review.
AB  - PURPOSE: Although self-management education is a key factor in the care for
      diabetes patients, its implementation in developing countries is not well
      documented. This systematic review considers the published literature on diabetes
      self-management education in high and low mortality developing countries. The aim
      is to provide a state of the art of current practices and assess program
      outcomes, cultural sensitivity, and accessibility to low literate patients.
      METHODS: The Cochrane Library, PubMed, MEDLINE, PsycInfo, and PsycArticles
      databases were searched for peer-reviewed articles on type 2 diabetes published
      in English between 2009 and 2013. The World Bank and WHO burden of disease
      criteria were applied to distinguish between developing countries with high and
      low mortality. Information was extracted using a validated checklist. RESULTS:
      Three reviews and 23 primary studies were identified, 18 of which were from low
      mortality developing countries. Studies from high mortality countries were mostly
      quasi-experimental, those from low mortality countries experimental.
      Interventions were generally effective on behavior change and patients' glycemic
      control in the short term (<=9 months). While 57% of the studies mentioned
      cultural tailoring of interventions, only 17% reported on training of providers,
      and 39% were designed to be accessible for people with low literacy. CONCLUSIONS:
      The limited studies available suggest that diabetes self-management education
      programs in developing countries are effective in the short term but must be
      tailored to conform to the cultural aspects of the target population.

PMID- 25392298
TI  - tRNA thiolation links translation to stress responses in Saccharomyces
      cerevisiae.
AB  - Although tRNA modifications have been well catalogued, the precise functions of
      many modifications and their roles in mediating gene expression are still being
      elucidated. Whereas tRNA modifications were long assumed to be constitutive, it
      is now apparent that the modification status of tRNAs changes in response to
      different environmental conditions. The URM1 pathway is required for thiolation
      of the cytoplasmic tRNAs tGlu(UUC), tGln(UUG), and tLys(UUU) in Saccharomyces
      cerevisiae. We demonstrate that URM1 pathway mutants have impaired translation,
      which results in increased basal activation of the Hsf1-mediated heat shock
      response; we also find that tRNA thiolation levels in wild-type cells decrease
      when cells are grown at elevated temperature. We show that defects in tRNA
      thiolation can be conditionally advantageous, conferring resistance to
      endoplasmic reticulum stress. URM1 pathway proteins are unstable and hence are
      more sensitive to changes in the translational capacity of cells, which is
      decreased in cells experiencing stresses. We propose a model in which a stress
      induced decrease in translation results in decreased levels of URM1 pathway
      components, which results in decreased tRNA thiolation levels, which further
      serves to decrease translation. This mechanism ensures that tRNA thiolation and
      translation are tightly coupled and coregulated according to need. 

PMID- 25392299
TI  - Axonal amyloid precursor protein and its fragments undergo somatodendritic
      endocytosis and processing.
AB  - Deposition of potentially neurotoxic Abeta fragments derived from amyloid
      precursor protein (APP) at synapses may be a key contributor to Alzheimer's
      disease. However, the location(s) of proteolytic processing and subsequent
      secretion of APP fragments from highly compartmentalized, euploid neurons that
      express APP and processing enzymes at normal levels is not well understood. To
      probe the behavior of endogenous APP, particularly in human neurons, we developed
      a system using neurons differentiated from human embryonic stem cells, cultured
      in microfluidic devices, to enable direct biochemical measurements from axons.
      Using human or mouse neurons in these devices, we measured levels of Abeta,
      sAPPalpha, and sAPPbeta secreted solely from axons. We found that a majority of
      the fragments secreted from axons were processed in the soma, and many were
      dependent on somatic endocytosis for axonal secretion. We also observed that APP
      and the beta-site APP cleaving enzyme were, for the most part, not dependent on
      endocytosis for axonal entry. These data establish that axonal entry and
      secretion of APP and its proteolytic processing products traverse different
      pathways in the somatodendritic compartment before axonal entry. 

PMID- 25392300
TI  - The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel
      regulator of SMN complex localization.
AB  - The survival motor neuron (SMN) complex fulfils essential functions in the
      assembly of snRNPs, which are key components in the splicing of pre-mRNAs. Little
      is known about the regulation of SMN complex activity by posttranslational
      modification despite its complicated phosphorylation pattern. Several
      phosphatases had been implicated in the regulation of SMN, including the nuclear
      phosphatases PPM1G and PP1gamma. Here we systematically screened all human
      phosphatase gene products for a regulatory role in the SMN complex. We used the
      accumulation of SMN in Cajal bodies of intact proliferating cells, which actively
      assemble snRNPs, as a readout for unperturbed SMN complex function. Knockdown of
      29 protein phosphatases interfered with SMN accumulation in Cajal bodies,
      suggesting impaired SMN complex function, among those the catalytically inactive,
      non-receptor-type tyrosine phosphatase PTPN23/HD-PTP. Knockdown of PTPN23 also
      led to changes in the phosphorylation pattern of SMN without affecting the
      assembly of the SMN complex. We further show interaction between SMN and PTPN23
      and document that PTPN23, like SMN, shuttles between nucleus and cytoplasm. Our
      data provide the first comprehensive screen for SMN complex regulators and
      establish a novel regulatory function of PTPN23 in maintaining a highly
      phosphorylated state of SMN, which is important for its proper function in snRNP
      assembly. 

PMID- 25392302
TI  - Kinetic control by limiting glutaredoxin amounts enables thiol oxidation in the
      reducing mitochondrial intermembrane space.
AB  - The mitochondrial intermembrane space (IMS) harbors an oxidizing machinery that
      drives import and folding of small cysteine-containing proteins without targeting
      signals. The main component of this pathway is the oxidoreductase Mia40, which
      introduces disulfides into its substrates. We recently showed that the IMS
      glutathione pool is maintained as reducing as that of the cytosol. It thus
      remained unclear how equilibration of protein disulfides with the IMS glutathione
      pool is prevented in order to allow oxidation-driven protein import. Here we
      demonstrate the presence of glutaredoxins in the IMS and show that limiting
      amounts of these glutaredoxins provide a kinetic barrier to prevent the
      thermodynamically feasible reduction of Mia40 substrates by the IMS glutathione
      pool. Moreover, they allow Mia40 to exist in a predominantly oxidized state.
      Consequently, overexpression of glutaredoxin 2 in the IMS results in a more
      reduced Mia40 redox state and a delay in oxidative folding and mitochondrial
      import of different Mia40 substrates. Our findings thus indicate that carefully
      balanced glutaredoxin amounts in the IMS ensure efficient oxidative folding in
      the reducing environment of this compartment. 

PMID- 25392301
TI  - Fission yeast profilin is tailored to facilitate actin assembly by the
      cytokinesis formin Cdc12.
AB  - The evolutionarily conserved small actin-monomer binding protein profilin is
      believed to be a housekeeping factor that maintains a general pool of unassembled
      actin. However, despite similar primary sequences, structural folds, and
      affinities for G-actin and poly-L-proline, budding yeast profilin ScPFY fails to
      complement fission yeast profilin SpPRF temperature-sensitive mutant cdc3-124
      cells. To identify profilin's essential properties, we built a combinatorial
      library of ScPFY variants containing either WT or SpPRF residues at multiple
      positions and carried out a genetic selection to isolate variants that support
      life in fission yeast. We subsequently engineered ScPFY(9-Mut), a variant
      containing nine substitutions in the actin-binding region, which complements cdc3
      124 cells. ScPFY(9-Mut), but not WT ScPFY, suppresses severe cytokinesis defects
      in cdc3-124 cells. Furthermore, the major activity rescued by ScPFY(9-Mut) is the
      ability to enhance cytokinesis formin Cdc12-mediated actin assembly in vitro,
      which allows cells to assemble functional contractile rings. Therefore an
      essential role of profilin is to specifically facilitate formin-mediated actin
      assembly for cytokinesis in fission yeast.

PMID- 25392308
TI  - Exploring the service and support needs of families with early-onset Alzheimer's
      disease.
AB  - Although often cast as a disease of later life, a growing number of people are
      being diagnosed with Alzheimer's disease in their 50s and 60s. Early-onset
      Alzheimer's disease (EOAD) poses special challenges and needs for individuals and
      their caregivers, such as employment and access to services. In this cross
      sectional study, the researchers surveyed 81 (N = 81) family caregivers to
      individuals with EOAD to identify service and support usage and need. Descriptive
      analyses revealed that families utilized a range of formal services (eg, adult
      day) and informal support from family and friends. In terms of challenges and
      needs, participants indicated that they struggled most with employment, benefits,
      and financial issues. Although most caregivers felt that they were coping well,
      they also indicated that their needs were not well understood by service
      providers and the public. These findings highlight the need to better understand
      and respond to the specific issues surrounding EOAD. 

PMID- 25392303
TI  - Ciliary transport regulates PDGF-AA/alphaalpha signaling via elevated mammalian
      target of rapamycin signaling and diminished PP2A activity.
AB  - Primary cilia are built and maintained by intraflagellar transport (IFT), whereby
      the two IFT complexes, IFTA and IFTB, carry cargo via kinesin and dynein motors
      for anterograde and retrograde transport, respectively. Many signaling pathways,
      including platelet- derived growth factor (PDGF)-AA/alphaalpha, are linked to
      primary cilia. Active PDGF-AA/alphaalpha signaling results in phosphorylation of
      Akt at two residues: P-Akt(T308) and P-Akt(S473), and previous work showed
      decreased P-Akt(S473) in response to PDGF-AA upon anterograde transport
      disruption. In this study, we investigated PDGF-AA/alphaalpha signaling via P
      Akt(T308) and P-Akt(S473) in distinct ciliary transport mutants. We found
      increased Akt phosphorylation in the absence of PDGF-AA stimulation, which we
      show is due to impaired dephosphorylation resulting from diminished PP2A activity
      toward P-Akt(T308). Anterograde transport mutants display low platelet-derived
      growth factor receptor (PDGFR)alpha levels, whereas retrograde mutants exhibit
      normal PDGFRalpha levels. Despite this, neither shows an increase in P-Akt(S473)
      or P-Akt(T308) upon PDGF-AA stimulation. Because mammalian target of rapamycin
      complex 1 (mTORC1) signaling is increased in ciliary transport mutant cells and
      mTOR signaling inhibits PDGFRalpha levels, we demonstrate that inhibition of
      mTORC1 rescues PDGFRalpha levels as well as PDGF-AA-dependent phosphorylation of
      Akt(S473) and Akt(T308) in ciliary transport mutant MEFs. Taken together, our
      data indicate that the regulation of mTORC1 signaling and PP2A activity by
      ciliary transport plays key roles in PDGF-AA/alphaalpha signaling. 

PMID- 25392304
TI  - CARM1 regulates astroglial lineage through transcriptional regulation of Nanog
      and posttranscriptional regulation by miR92a.
AB  - Coactivator-associated arginine methyltransferase (CARM1/PRMT4)-mediated
      transcriptional coactivation and arginine methylation is known to regulate
      various tissue-specific differentiation events. Although CARM1 is expressed in
      the neural crest region in early development, coinciding with early neuronal
      progenitor specification, the role of CARM1 in any neuronal developmental
      pathways has been unexplored. Using a specific small-molecule inhibitor of CARM1
      mediated H3R17 methylation in human embryonic stem cell line, we find that H3R17
      methylation contributes to the maintenance of the astroglial cell population. A
      network of regulation was observed on the miR92a promoter by which H3R17
      responsive Nanog bound to the miR92a promoter decreased upon inhibition,
      resulting in an abnormal gene expression program influencing the glial lineage.
      This was also true in zebrafish, in which, with the help of CARM1 inhibitor and
      CARM1 morpholinos, we show that inhibition of H3R17 methylation results in
      defective glial cell morphology and a sensory defect in a subpopulation. A gain
      of-function strategy in which mCARM1 was introduced in the morpholino-treated
      embryos exhibited recovery of the sensory defect phenotype. This study thus
      establishes the functional cooperation between arginine methylation and microRNA
      expression in the neuronal developmental process, with potential implications in
      sensory development pathways. 

PMID- 25392309
TI  - Human children rely more on social information than chimpanzees do.
AB  - Human societies are characterized by more cultural diversity than chimpanzee
      communities. However, it is currently unclear what mechanism might be driving
      this difference. Because reliance on social information is a pivotal
      characteristic of culture, we investigated individual and social information
      reliance in children and chimpanzees. We repeatedly presented subjects with a
      reward-retrieval task on which they had collected conflicting individual and
      social information of equal accuracy in counterbalanced order. While both species
      relied mostly on their individual information, children but not chimpanzees
      searched for the reward at the socially demonstrated location more than at a
      random location. Moreover, only children used social information adaptively when
      individual knowledge on the location of the reward had not yet been obtained.
      Social information usage determines information transmission and in conjunction
      with mechanisms that create cultural variants, such as innovation, it facilitates
      diversity. Our results may help explain why humans are more culturally
      diversified than chimpanzees. 

PMID- 25392310
TI  - The ecology of primate material culture.
AB  - Tool use in extant primates may inform our understanding of the conditions that
      favoured the expansion of hominin technology and material culture. The 'method of
      exclusion' has, arguably, confirmed the presence of culture in wild animal
      populations by excluding ecological and genetic explanations for geographical
      variation in behaviour. However, this method neglects ecological influences on
      culture, which, ironically, may be critical for understanding technology and thus
      material culture. We review all the current evidence for the role of ecology in
      shaping material culture in three habitual tool-using non-human primates:
      chimpanzees, orangutans and capuchin monkeys. We show that environmental
      opportunity, rather than necessity, is the main driver. We argue that a better
      understanding of primate technology requires explicit investigation of the role
      of ecological conditions. We propose a model in which three sets of factors,
      namely environment, sociality and cognition, influence invention, transmission
      and retention of material culture. 

PMID- 25392311
TI  - Glucocorticoid metabolism in the in ovo environment modulates exposure to
      maternal corticosterone in Japanese quail embryos (Coturnix japonica).
AB  - Maternal effects have gained attention as a method by which mothers may alter the
      physiological condition and phenotype of their offspring based upon current
      environmental conditions. The physiological and phenotypic outcomes of
      glucocorticoid-mediated maternal effects have been extensively studied in a
      variety of vertebrates; however, the underlying mechanism is currently unclear.
      Here, we injected tritiated corticosterone into the yolks of freshly laid
      Japanese quail eggs (Coturnix japonica) and traced its movement and metabolism
      through the in ovo development period. We found that corticosterone was
      extensively conjugated throughout the egg by the end of development, and while
      minimal corticosterone was detected within the embryo during development,
      accumulation of a conjugated metabolite in the embryo started to occur on day 6
      of development. Because no movement and metabolism of corticosterone occurred in
      infertile eggs, our findings suggest that embryos are not passive recipients of
      maternal steroids, but instead appear to possess extensive metabolic
      capabilities, which may modulate their exposure to maternal steroids. 

PMID- 25392312
TI  - Why are so many trees hollow?
AB  - In many living trees, much of the interior of the trunk can be rotten or even
      hollowed out. Previously, this has been suggested to be adaptive, with microbial
      or animal consumption of interior wood producing a rain of nutrients to the soil
      beneath the tree that allows recycling of those nutrients into new growth via the
      trees roots. Here I propose an alternative (non-exclusive) explanation: such loss
      of wood comes at very little cost to the tree and so investment in costly
      chemical defence of this wood is not economic. I discuss how this theory can be
      tested empirically. 

PMID- 25392313
TI  - Influence of climate on the presence of colour polymorphism in two montane
      reptile species.
AB  - The coloration of ectotherms plays an important role in thermoregulation
      processes. Dark individuals should heat up faster and be able to reach a higher
      body temperature than light individuals and should therefore have benefits in
      cool areas. In central Europe, montane local populations of adder (Vipera berus)
      and asp viper (Vipera aspis) exhibit a varying proportion of melanistic
      individuals. We tested whether the presence of melanistic V. aspis and V. berus
      could be explained by climatic conditions. We measured the climatic niche
      position and breadth of monomorphic (including strictly patterned individuals)
      and polymorphic local populations, calculated their niche overlap and tested for
      niche equivalency and similarity. In accordance with expectations, niche overlap
      between polymorphic local populations of both species is high, and even higher
      than that of polymorphic versus monomorphic montane local populations of V.
      aspis, suggesting a predominant role of melanism in determining the niche of
      ectothermic vertebrates. However, unexpectedly, the niche of polymorphic local
      populations of both species is narrower than that of monomorphic ones, indicating
      that colour polymorphism does not always enable the exploitation of a greater
      variability of resources, at least at the intraspecific level. Overall, our
      results suggest that melanism might be present only when the thermoregulatory
      benefit is higher than the cost of predation. 

PMID- 25392314
TI  - Male sperm storage compromises sperm motility in guppies.
AB  - Sperm senescence can have important evolutionary implications due to its
      deleterious effects on sperm quality and offspring performance. Consequently, it
      has been argued that polyandry (female multiple mating) may facilitate the
      selection of younger, and therefore competitively superior, sperm when ejaculates
      from multiple males compete for fertilization. Surprisingly, however, unequivocal
      evidence that sperm ageing influences traits that underlie sperm competitiveness
      is lacking. Here, we used a paired experimental design that compares sperm
      quality between 'old' and 'young' ejaculates from individual male guppies
      (Poecilia reticulata). We show that older sperm exhibit significant reductions in
      sperm velocity compared with younger sperm from the same males. We found no
      evidence that the brightness of the male's orange (carotenoid) spots, which are
      thought to signal resistance to oxidative stress (and thus age-related declines
      in sperm fitness), signals a male's ability to withstand the deleterious effects
      of sperm ageing. Instead, polyandry may be a more effective strategy for females
      to minimize the likelihood of being fertilized by aged sperm. 

PMID- 25392315
TI  - Oxygen isotope values in bone carbonate and collagen are consistently offset for
      New World monkeys.
AB  - Stable oxygen isotopes are increasingly used in ecological research. Here, I
      present oxygen isotope (delta(18)O) values for bone carbonate and collagen from
      howler monkeys (Alouatta palliata), spider monkeys (Ateles geoffroyi) and
      capuchins (Cebus capucinus) from three localities in Costa Rica. There are
      apparent differences in delta(18)Ocarbonate and delta(18)Ocollagen among species.
      Monkeys from moist forest have significantly lower isotope values than those from
      drier localities. Because patterns are similar for both substrates,
      discrimination (Delta) between delta(18)Ocarbonate and delta(18)Ocollagen is
      relatively consistent among species and localities (17.6 +/- 0.90/00). Although
      this value is larger than that previously obtained for laboratory rats,
      consistency among species and localities suggests it can be used to compare
      delta(18)Ocarbonate and delta(18)Ocollagen for monkeys, and potentially other
      medium-bodied mammals. Establishing discrimination for oxygen between these
      substrates for wild monkeys provides a foundation for future environmental and
      ecological research on modern and ancient organisms. 

PMID- 25392316
TI  - Inbreeding-related trade-offs in stress resistance in the ant Formica exsecta.
AB  - Inbred individuals and populations are predicted to suffer from inbreeding
      depression, especially in times of stress. Under natural conditions, organisms
      are exposed to more than one stressor at any one time, highlighting the
      importance of stress resistance traits. We studied how inbreeding- and immunity
      related traits are correlated under different dietary conditions in the ant
      Formica exsecta. Its natural diet varies in the amount and nature of plant
      secondary compounds and the level of free radicals, all of which require
      detoxification to maintain organismal homeostasis. We found that inbreeding
      decreased general antibacterial activity under dietary stress, suggesting
      inbreeding-related physiological trade-offs. 

PMID- 25392317
TI  - Better the devil you know: avian predators find variation in prey toxicity
      aversive.
AB  - Toxic prey that signal their defences to predators using conspicuous warning
      signals are called 'aposematic'. Predators learn about the toxic content of
      aposematic prey and reduce their attacks on them. However, through regulating
      their toxin intake, predators will include aposematic prey in their diets when
      the benefits of gaining the nutrients they contain outweigh the costs of
      ingesting the prey's toxins. Predators face a problem when managing their toxin
      intake: prey sharing the same warning signal often vary in their toxicities.
      Given that predators should avoid uncertainty when managing their toxin intake,
      we tested whether European starlings (Sturnus vulgaris) preferred to eat fixed
      defence prey (where all prey contained a 2% quinine solution) to mixed-defence
      prey (where half the prey contained a 4% quinine solution and the other half
      contained only water). Our results support the idea that predators should be more
      'risk-averse' when foraging on variably defended prey and suggest that variation
      in toxicity levels could be a form of defence. 

PMID- 25392318
TI  - Non-Gaussian diffusion MRI of gray matter is associated with cognitive impairment
      in multiple sclerosis.
AB  - BACKGROUND: Non-Gaussian diffusion imaging by using diffusional kurtosis imaging
      (DKI) allows assessment of isotropic tissue as of gray matter (GM), an important
      limitation of diffusion tensor imaging (DTI). OBJECTIVE: In this study, we
      describe DKI and DTI metrics of GM in multiple sclerosis (MS) patients and their
      association with cognitive deficits. METHODS: Thirty-four patients with relapsing
      remitting MS and 17 controls underwent MRI on a 3T scanner including a sequence
      for DKI with 30 diffusion directions and 3b values for each direction. Mean
      kurtosis (MK), mean diffusivity and fractional anisotropy (FA) of cortical and
      subcortical GM were measured using histogram analysis. Spearman rank correlations
      were used to characterize associations among imaging measures and
      clinical/neuropsychological scores. RESULTS: In cortical GM, a significant
      decrease of MK (0.68 vs. 0.73; p < 0.001) and increase of FA (0.16 vs. 0.13; p <
      0.001) was found in patients compared to controls. Decreased cortical MK was
      correlated with poor performance on the Delis-Kaplan Executive Function System
      test (r = 0.66, p = 0.01). CONCLUSION: Mean kurtosis is sensitive to abnormality
      in GM of MS patients and can provide information that is complementary to that of
      conventional DTI-derived metrics. The association between MK and cognitive
      deficits suggests that DKI might serve as a clinically relevant biomarker for
      cortical injury.

PMID- 25392319
TI  - Prognostic biomarkers of IFNb therapy in multiple sclerosis patients.
AB  - BACKGROUND: Interferon beta (IFNb) reduces relapse frequency and disability
      progression in patients with multiple sclerosis (MS). OBJECTIVES: Early
      identification of prognostic biomarkers of IFNb-treated patients will allow more
      effective management of MS. METHODS: The IMPROVE study evaluated subcutaneous
      IFNb versus placebo in 180 patients with relapsing-remitting MS. Magnetic
      resonance imaging scans, clinical assessments, and blood samples were obtained at
      baseline and every 4 weeks from every participant. Thirty-nine biomarkers (32
      transcripts; seven proteins) were studied in 155 patients from IMPROVE.
      Therapeutic response was defined by absence of new combined unique lesions,
      relapses, and sustained increase in Expanded Disability Status Scale over 1 year.
      A machine learning approach was used to examine the association between biomarker
      expression and treatment response. RESULTS: While baseline levels of individual
      genes were relatively poor predictors, combinations of three genes were able to
      identify subjects with sub-optimal therapeutic responses. The triplet
      CASP2/IRF4/IRF6, previously identified in an independent dataset, was tested
      among other combinations. This triplet showed acceptable predictive accuracy
      (0.68) and specificity (0.88), but had relatively low sensitivity (0.22)
      resulting in an area under the curve (AUC) of 0.63. Other combinations of
      biomarkers resulted in AUC of up to 0.80 (e.g. CASP2/IL10/IL12Rb1). CONCLUSIONS:
      Baseline expression, or induction ratios, of specific gene combinations correlate
      with future therapeutic response to IFNb, and have the potential to be
      prognostically useful.

PMID- 25392320
TI  - Significant clinical worsening after natalizumab withdrawal: Predictive factors.
AB  - We aimed to single out multiple sclerosis (MS) cases with poor outcome after
      natalizumab withdrawal and to identify predictive variables. We ascertained 47
      withdrawals, and compared their pre- and post-natalizumab periods. We objectively
      defined significant clinical worsening after natalizumab withdrawal as a 2-step
      increase in Expanded Disability Status Scale (EDSS). We performed regression
      models. As a group, post-natalizumab annualized relapse rate (ARR) was lower in
      the post-natalizumab period, and there were no differences in the mean number of
      gadolinium (Gd)-enhancing lesions between pre- and post-natalizumab magnetic
      resonance imaging (MRI). Corticosteroid treatment did not change the outcomes.
      Eight patients (19%) presented significant clinical worsening after natalizumab
      withdrawal, which was predicted by a higher baseline EDSS and a 1-step EDSS
      increase while on natalizumab. 

PMID- 25392321
TI  - Altered basal ganglia functional connectivity in multiple sclerosis patients with
      fatigue.
AB  - BACKGROUND: Fatigue is one of the most frequent and disabling symptoms in
      multiple sclerosis, but its pathophysiological mechanisms are poorly understood.
      It is in particular unclear whether and how fatigue relates to structural and
      functional brain changes. OBJECTIVE: We aimed to analyse the association of
      fatigue severity with basal ganglia functional connectivity, basal ganglia
      volumes, white matter integrity and grey matter density. METHODS: In 44 patients
      with relapsing-remitting multiple sclerosis and 20 age- and gender-matched
      healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based
      morphometry was performed. RESULTS: In comparison with healthy controls, patients
      showed alteration of grey matter density, white matter integrity, basal ganglia
      volumes and basal ganglia functional connectivity. No association of fatigue
      severity with grey matter density, white matter integrity and basal ganglia
      volumes was observed within patients. In contrast, fatigue severity was
      negatively correlated with functional connectivity of basal ganglia nuclei with
      medial prefrontal cortex, precuneus and posterior cingulate cortex in patients.
      Furthermore, fatigue severity was positively correlated with functional
      connectivity between caudate nucleus and motor cortex. CONCLUSION: Fatigue is
      associated with distinct alterations of basal ganglia functional connectivity
      independent of overall disability. The pattern of connectivity changes suggests
      that disruption of motor and non-motor basal ganglia functions, including
      motivation and reward processing, contributes to fatigue pathophysiology in
      multiple sclerosis.

PMID- 25392323
TI  - How safe is natalizumab during pregnancy?

PMID- 25392322
TI  - Newly produced T and B lymphocytes and T-cell receptor repertoire diversity are
      reduced in peripheral blood of fingolimod-treated multiple sclerosis patients.
AB  - BACKGROUND: Fingolimod inhibits lymphocyte egress from lymphoid tissues, thus
      altering the composition of the peripheral lymphocyte pool of multiple sclerosis
      patients. OBJECTIVE: The objective of this paper is to evaluate whether
      fingolimod determines a decrease of newly produced T- and B-lymphocytes in the
      blood and a reduction in the T-cell receptor repertoire diversity that may affect
      immune surveillance. METHODS: Blood samples were obtained from multiple sclerosis
      patients before fingolimod therapy initiation and then after six and 12 months.
      Newly produced T and B lymphocytes were measured by quantifying T-cell receptor
      excision circles and K-deleting recombination excision circles by real-time PCR,
      while recent thymic emigrants, naive CD8(+) lymphocytes, immature and naive B
      cells were determined by immune phenotyping. T-cell receptor repertoire was
      analyzed by complementarity determining region 3 spectratyping. RESULTS: Newly
      produced T and B lymphocytes were significantly reduced in peripheral blood of
      fingolimod-treated patients. The decrease was particularly evident in the T-cell
      compartment. T-cell repertoire restrictions, already present before therapy,
      significantly increased after 12 months of treatment. CONCLUSIONS: These results
      do not have direct clinical implications but they may be useful for further
      understanding the mode of action of this immunotherapy for multiple sclerosis
      patients.

PMID- 25392324
TI  - Increased anti-KIR4.1 antibodies in multiple sclerosis: could it be a marker of
      disease relapse?
AB  - BACKGROUND: Screening of putative autoimmune targets in multiple sclerosis (MS)
      revealed a proportion of patients carrying antibodies (Abs) against KIR4.1, a
      potassium channel that shares functional properties with AQP4. Both are localized
      at the perivascular astrocytic processes. AIMS: To measure anti-KIR4.1 Abs in the
      serum of MS and neuromyelitis optica (NMO) patients, and to identify the clinical
      and laboratory characteristics of patients harboring anti-KIR4.1 Abs. METHODS: We
      measured anti-KIR4.1 Abs in serum, using the peptide KIR4.1 (83-120) enzyme
      linked immunosorbent assay (ELISA). RESULTS: Serum levels of anti-KIR4.1 Abs were
      significantly higher in MS and NMO patients than in healthy controls (HCs); with
      Abs detected in 21 of 80, 10 of 45, and 2 of 32 individuals, respectively (MS
      versus HC, p < 0.05). The level of anti-KIR4.1 Abs was significantly higher
      during MS relapse, versus remission (p = 0.04). The clinical characteristics of
      our study patients did not vary based on KIR4.1 positivity. CONCLUSIONS: Anti
      KIR4.1 Abs were found in similar proportions of patients with MS and NMO, at a
      significantly higher level than observed in HCs; consequently, the presence of
      Abs does not discriminate between these demyelinating diseases. However, anti
      KIR4.1 Ab levels differed in MS patients during relapse and remission; as such,
      they may represent a marker of disease exacerbation.

PMID- 25392325
TI  - A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody
      against the envelope protein of multiple sclerosis-associated endogenous
      retrovirus in multiple sclerosis patients.
AB  - BACKGROUND: GNbAC1 is an immunoglobulin (IgG4) humanised monoclonal antibody
      against multiple sclerosis-associated retrovirus (MSRV)-Env, a protein of
      endogenous retroviral origin, expressed in multiple sclerosis (MS) lesions, which
      is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation.
      OBJECTIVE: This is a randomised, double-blind placebo-controlled dose-escalation
      study followed by a six-month open-label phase to test GNbAC1 in MS patients. The
      primary objective was to assess GNbAC1 safety in MS patients, and the other
      objectives were pharmacokinetic and pharmacodynamic assessments. METHODS: Ten MS
      patients were randomised into two cohorts to receive a single intravenous
      infusion of GNbAC1/placebo at doses of 2 or 6 mg/kg. Then all patients received
      five infusions of GNbAC1 at 2 or 6 mg/kg at four-week intervals in an open-label
      setting. Safety, brain magnetic resonance imaging (MRI), pharmacokinetics,
      immunogenicity, cytokines and MSRV RNA expression were studied. RESULTS: All
      patients completed the study. GNbAC1 was well tolerated in all patients. GNbAC1
      pharmacokinetics is dose-linear with mean elimination half-life of 27-37 d. Anti
      GNbAC1 antibodies were not detected. Cytokine analysis did not indicate an
      adverse effect. MSRV-transcripts showed a decline after the start of treatment.
      Nine patients had stable brain lesions at MRI. CONCLUSION: The safety,
      pharmacokinetic profile, and pharmacodynamic responses to GNbAC1 are favourable
      in MS patients over a six-month treatment period.

PMID- 25392326
TI  - We can compare the relative efficacy of multiple sclerosis medications by
      examining the results of independent clinical trials: yes.

PMID- 25392327
TI  - Higher weight in adolescence and young adulthood is associated with an earlier
      age at multiple sclerosis onset.
AB  - BACKGROUND: Growing evidence suggests an association between adolescent obesity
      and increased risk of multiple sclerosis (MS). OBJECTIVE: The objective of this
      paper is to investigate whether weight or body mass index (BMI) in adolescence
      and young adulthood was associated with age at MS symptom onset. METHODS: Our
      cohort is comprised of a sub-group of 184 women enrolled in the New York State MS
      Consortium registry. Individuals were asked to recall their weight at the time of
      first menstruation and at age 25. BMI was calculated accordingly for age 25.
      Regression analyses were carried out to investigate the association between
      weight or BMI and age at onset. RESULTS: Weight at menarche was significantly
      related to younger age at symptom onset (beta = -0.073, p = 0.001). These results
      were also found at age 25 for weight (beta = -0.080, p < 0.001) and BMI (beta = 
      0.448, p = 0.001). Significantly earlier disease onset (26.9 years +/-9.9) was
      observed in individuals who were overweight at 25 compared to those who were not
      overweight (32.1 years +/-9.2, p = 0.006). CONCLUSIONS: Women who reported higher
      weight in adolescence and BMI in early adulthood were younger at MS onset. Future
      research should investigate whether there is a causal link between body weight
      and MS, as prevention lifestyle and dietary interventions could be implemented.

PMID- 25392329
TI  - The best basic science paper in MS in 2013: Antimuscarinic therapies in
      remyelination.

PMID- 25392328
TI  - A new risk variant for multiple sclerosis at the immunoglobulin heavy chain locus
      associates with intrathecal IgG, IgM index and oligoclonal bands.
AB  - BACKGROUND: Recent findings have shown a correlation between the intrathecal IgG
      index and variants at the immunoglobulin heavy chain (IGHC) locus in patients
      with multiple sclerosis (MS). OBJECTIVES: The objective of this paper is to
      analyse the association of the locus with MS susceptibility and its relationship
      with intrathecal immunoglobulin (Ig) parameters. METHODS: We genotyped the
      rs11621145 variant, located at the IGHC locus, in 2726 patients with MS and 2133
      healthy controls. Associations of intrathecal IgG and IgM indexes with rs11621145
      were analysed by linear regression analysis in 538 MS patients. RESULTS: We found
      that rs11621145 showed statistically significant evidence for association with
      susceptibility to MS (odds ratio = 0.69, p = 1.053E-09), though validation of
      this result in additional cohorts would be desirable. We confirmed the
      association between the IgG index and the rs11621145 (p = 6.85E-07, Beta =
      0.207). Furthermore, rs11621145 was inversely correlated with IgM index (p =
      7.24E-04, Beta = -0.277), and therefore marks a decreased likelihood of
      presenting IgM oligoclonal bands (odds ratio = 0.38, p = 2.35E-06). CONCLUSIONS:
      Our results suggest that the polymorphism of the IGHC locus could be altering the
      switching of the Ig isotype in B cells and it may be interfering with T-dependent
      and T-independent antibody responses.

PMID- 25392330
TI  - Brain atrophy in natalizumab-treated patients: A 3-year follow-up.
AB  - BACKGROUND: A pseudoatrophy effect has been held responsible for the lack of net
      impact of natalizumab on brain volume outcomes in 2-year trials, but no data are
      available beyond 24 months. OBJECTIVE: We aimed to investigate brain volume
      dynamics in natalizumab-treated patients in up to 3 years after therapy
      initiation with clinical correlations. METHODS: Patients on natalizumab for at
      least 3 years were clinically assessed 3-monthly. Magnetic resonance imaging
      scans were performed at baseline and yearly. Brain volume changes were obtained
      with SIENA. Multivariate models were used to investigate the association between
      baseline inflammation and changes in brain volume and disability. RESULTS: Sixty
      two patients with multiple sclerosis were analysed. Mean age and disease duration
      were 34.7 (SD: 8.3) and 10.4 (SD: 6.6) years. Presence of gadolinium enhancement
      at baseline was not associated with Expanded Disability Status Scale changes
      (p=0.468), but was associated with larger brain volume decreases (p=0.005) in the
      first (p=0.024) and second year (p=0.019) but not in the third year (p=0.863).
      Brain volume changes at 12 and 36 months were marginally associated with
      disability status at month 12 (p=0.094) and 36 (p=0.084), respectively.
      CONCLUSIONS: Baseline inflammation affects brain volume measures up to 24 months
      after natalizumab initiation. A marginal association of brain volume changes with
      disability is present.

PMID- 25392331
TI  - High inbreeding in the Faroe Islands does not appear to constitute a risk factor
      for multiple sclerosis.
AB  - BACKGROUND: Large population-based genome-wide association studies have
      identified several multiple sclerosis (MS) genetic risk variants, but the
      existing missing heritability warrants different strategies. Isolated populations
      offer an alternative way of searching for rare genetic variants and evaluating
      the possible role of consanguinity in the development of MS. Studies of
      consanguinity and MS risk have yielded conflicting results. OBJECTIVES: In this
      study we investigated the role of consanguinity on MS risk in the relatively
      isolated Faroe Islands, which have a presumed high level of inbreeding. METHODS:
      A total of 29 cases and 28 matched controls were genotyped and assessed for
      inbreeding coefficients, number of runs of homozygosity (ROH) at different
      lengths and observed number of homozygotes as measures of relatedness. Parametric
      and non-parametric statistical models were applied. RESULTS: Both cases and
      controls exhibited considerable relatedness demonstrated by very high inbreeding
      coefficients, large number of observed homozygotes and many long ROH. However,
      apart from the number of ROH >= 2.5 mega base pairs, no significant differences
      between the two groups were observed. CONCLUSIONS: Overall, no significant
      difference between cases and controls were found, indicating that consanguinity
      in itself does not appear to be an important risk factor for MS in the population
      of the Faroe Islands.

PMID- 25392332
TI  - Cognitive impairment in paediatric multiple sclerosis patients is not related to
      cortical lesions.
AB  - We investigated the contribution of cortical lesions to cognitive impairment in
      41 paediatric MS patients. Thirteen (32%) paediatric MS patients were considered
      as cognitively impaired. T2-hyperintense and T1-hypointense white matter lesion
      volumes did not differ between cognitively impaired and cognitively preserved MS
      patients. Cortical lesions number, cortical lesions volume and grey matter volume
      did not differ between cognitively impaired and cognitively preserved patients,
      whereas white matter volume was significantly lower in cognitively impaired
      versus cognitively preserved MS patients (p=0.01). Contrary to adult MS, cortical
      lesions do not seem to contribute to cognitive impairment in paediatric MS
      patients, which is likely driven by white matter damage. 

PMID- 25392333
TI  - Axonal conduction in multiple sclerosis: A combined magnetic resonance imaging
      and electrophysiological study of the medial longitudinal fasciculus.
AB  - OBJECTIVE: The objective of this paper is to inform the pathophysiology of medial
      longitudinal fasciculus (MLF) axonal dysfunction in patients with internuclear
      ophthalmoplegia (INO) due to multiple sclerosis (MS), and develop a composite
      structural-functional biomarker of axonal and myelin integrity in this tract.
      METHODS: Eighteen patients with definite MS and clinically suspected INO
      underwent electrical vestibular stimulation and search-coil eye movement
      recording. Components of the electrically evoked vestibulo-ocular reflex (eVOR)
      were analyzed to probe the latency and fidelity of MLF axonal conduction. The MLF
      and T2-visible brainstem lesions were defined by high-resolution MRI. White
      matter integrity was determined by diffusion-weighted imaging metrics. RESULTS:
      eVOR onset latency was positively correlated with MLF lesion length (left: r =
      0.66, p = 0.004; right: r = 0.75, p = 0.001). The mean conduction velocity (+/
      SD) within MLF lesions was estimated at 2.72 (+/-0.87) m/s. eVOR onset latency
      correlated with normalized axial diffusivity (r = 0.66, p < 0.001) and fractional
      anisotropy (r = 0.44, p = 0.02) after exclusion of cases with ipsilateral
      vestibular root entry zone lesions. CONCLUSIONS: Axonal conduction velocity
      through lesions involving the MLF was reduced below levels predicted for natively
      myelinated and remyelinated axons. Composite in vivo biomarkers enable
      delineation of axonal from myelin processes and may provide a crucial role in
      assessing efficacy of novel reparative therapies in MS.

PMID- 25392334
TI  - We can compare the relative efficacy of multiple sclerosis medications by
      examining the results of independent clinical trials: no.

PMID- 25392335
TI  - Human interferon regulatory factor 5 homologous epitopes of Epstein-Barr virus
      and Mycobacterium avium subsp. paratuberculosis induce a specific humoral and
      cellular immune response in multiple sclerosis patients.
AB  - BACKGROUND: A large number of reports indicate the association of Epstein-Barr
      virus (EBV), and Mycobacterium avium subsp. paratuberculosis (MAP) with multiple
      sclerosis (MS). OBJECTIVE: To gain a better understanding of the role of these
      two pathogens, we investigated the host response induced by selected antigenic
      peptides. METHODS: We examined both humoral and cell-mediated responses against
      peptides deriving from EBV tegument protein BOLF1, the MAP_4027 and the human
      interferon regulatory factor 5 (IRF5424-434) homolog in several MS patients and
      healthy controls (HCs). RESULTS: Antibodies against these peptides were highly
      prevalent in MS patients compared to HCs. Concerning MS patients, BOLF1305-320,
      MAP_402718-32 and IRF5424-434 peptides were able to induce mainly Th1-related
      cytokines secretion, whereas Th2-related cytokines were down-regulated. Flow
      cytometry analyses performed on a subset of MS patients highlighted that these
      peptides were capable of inducing the release of pro-inflammatory cytokines: IFN
      gamma and TNF-alpha by CD4(+) and CD8(+) T lymphocytes, and IL-6 and TNF-alpha by
      CD14(+) monocyte cells. CONCLUSION: Our data demonstrated that both EBV and MAP
      epitopes elicit a consistent humoral response in MS patients compared to HCs, and
      that the aforementioned peptides are able to induce a T-cell-mediated response
      that is MS correlated.

PMID- 25392336
TI  - The best basic science paper in multiple sclerosis in 2013: Disease specific
      molecular events in cortical multiple sclerosis lesions.

PMID- 25392337
TI  - Tailored balance exercises on people with multiple sclerosis: A pilot randomized,
      controlled study.
AB  - BACKGROUND: Altered integration of signals from visual (VIS), somatosensory
      (PROP) and vestibular system (VEST) lead to balance control impairments affecting
      the daily living activities of patients with multiple sclerosis (PwMS). As a
      consequence, tailored interventions could be crucial in improving efficacy of
      balance rehabilitation treatments. OBJECTIVE: The objective of this paper is to
      assess the efficacy of tailored rehabilitation treatments for balance disorders
      based on visual, somatosensory and vestibular deficits versus traditional
      rehabilitation exercises. METHODS: Thirty-two PwMS were assessed with the Berg
      Balance Scale (BBS), the composite score (CS) obtained by computerized dynamic
      posturography (CDP) test and the Modified Fatigue Impact Scale (MFIS). Based on
      CDP analysis, prevalent VIS, PROP or VEST deficits were identified and patients
      randomly allocated to a personalized (PRG) or traditional (TRG) rehabilitation
      group. RESULTS: BBS score showed a significant difference between pre- and post
      treatment scores of 6.3 and 2.0 points respectively for PRG and TRG. CS showed a
      significant difference between pre- and post-treatment scores of 16.6 and 7.6
      points respectively for PRG and TRG. No interaction effect was found for MFIS
      score. CONCLUSIONS: BBS and CS showed changes in the PRG group that met clinical
      relevant difference, underlining that tailored rehabilitation interventions based
      on patient-specific sensory system impairment could improve balance and postural
      control in PwMS.

PMID- 25392338
TI  - Development and validation of an administrative data algorithm to estimate the
      disease burden and epidemiology of multiple sclerosis in Ontario, Canada.
AB  - BACKGROUND: Few studies have assessed the accuracy of administrative data for
      identifying multiple sclerosis (MS) patients. OBJECTIVES: To validate
      administrative data algorithms for MS, and describe the burden and epidemiology
      over time in Ontario, Canada. METHODS: We employed a validated search strategy to
      identify all MS patients within electronic medical records, to identify patients
      with and without MS (reference standard). We then developed and validated
      different combinations of administrative data for algorithms. The most accurate
      algorithm was used to estimate the burden and epidemiology of MS over time.
      RESULTS: The accuracy of the algorithm of one hospitalisation or five physician
      billings over 2 years provided both high sensitivity (84%) and positive
      predictive value (86%). Application of this algorithm to provincial data
      demonstrated an increasing cumulative burden of MS, from 13,326 patients (0.14%)
      in 2000 to 24,647 patients in 2010 (0.22%). Age-and-sex standardised prevalence
      increased from 133.9 to 207.3 MS patients per 100,000 persons in the population,
      from 2000 - 2010. During this same period, age-and-sex-standardised incidence
      varied from 17.9 to 19.4 patients per 100,000 persons. CONCLUSIONS: MS patients
      can be accurately identified from administrative data. Our findings illustrated a
      rising prevalence of MS over time. MS incidence rates also appear to be rising
      since 2009.

PMID- 25392339
TI  - Natalizumab exerts a suppressive effect on surrogates of B cell function in blood
      and CSF.
AB  - BACKGROUND: Natalizumab for multiple sclerosis (MS) increases the risk of
      progressive multifocal leukoencephalopathy (PML). OBJECTIVE: We aimed to assess
      the effect of natalizumab on cellular composition and functional B cell
      parameters including patients with natalizumab-associated PML (n=37). METHODS:
      Cellular composition by flow cytometry, levels of immunoglobulin (Ig)G/IgM by
      immunonephelometry, and oligoclonal bands by isoelectric focusing were studied in
      blood and cerebrospinal fluid. RESULTS: In MS patients treated with natalizumab
      without PML (n=59) the proportion of CD19+ B cells was higher in blood, but lower
      in cerebrospinal fluid compared with MS patients not treated with natalizumab
      (n=17). The CD4/CD8-ratio in cerebrospinal fluid was lower, and IgG and IgM
      levels as well as the IgG index dropped in longitudinal samples during
      natalizumab therapy. Oligoclonal bands persisted, but the total amount of the
      intrathecally produced IgG fraction, and the polyclonal intrathecal IgG
      reactivity to measles, rubella, and zoster declined. At the time of diagnosis of
      PML patients with natalizumab-associated PML had low total IgG levels in blood
      and cerebrospinal fluid. CONCLUSIONS: Natalizumab impacts B and T cell
      distribution and exerts an inhibitory effect on surrogates of B cell function in
      periphery and in cerebrospinal fluid, potentially contributing to the increased
      risk of developing PML.

PMID- 25392340
TI  - Attention-based classification pattern, a research domain criteria framework, in
      youths with bipolar disorder and attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: The National Institute of Mental Health has initiated the Research
      Domain Criteria (RDoC) project. Instead of using disorder categories as the basis
      for grouping individuals, the RDoC suggests finding relevant dimensions that can
      cut across traditional disorders. Our aim was to use the RDoC's framework to
      study patterns of attention deficit based on results of Conners' Continuous
      Performance Test (CPT II) in youths diagnosed with bipolar disorder (BD),
      attention-deficit/hyperactivity disorder (ADHD), BD+ADHD and controls. METHOD:
      Eighteen healthy controls, 23 patients with ADHD, 10 with BD and 33 BD+ADHD aged
      12-17 years old were assessed. Pattern recognition was used to partition subjects
      into clusters based simultaneously on their performance in all CPT II variables.
      A Fisher's linear discriminant analysis was used to build a classifier. RESULTS:
      Using cluster analysis, the entire sample set was best clustered into two new
      groups, A and B, independently of the original diagnoses. ADHD and BD+ADHD were
      divided almost 50% in each subgroup, and there was an agglomeration of controls
      and BD in group B. Group A presented a greater impairment with higher means in
      all CPT II variables and lower Children's Global Assessment Scale. We found a
      high cross-validated classification accuracy for groups A and B: 95.2%.
      Variability of response time was the strongest CPT II measure in the
      discriminative pattern between groups A and B. CONCLUSION: Our classificatory
      exercise supports the concept behind new approaches, such as the RDoC framework,
      for child and adolescent psychiatry. Our approach was able to define clinical
      subgroups that could be used in future pathophysiological and treatment studies.

PMID- 25392341
TI  - The dose-related effects of dexmedetomidine on renal functions and serum
      neutrophil gelatinase-associated lipocalin values after coronary artery bypass
      grafting: a randomized, triple-blind, placebo-controlled study.
AB  - OBJECTIVES: Acute kidney failure after coronary artery bypass grafting (CABG) is
      a serious complication that increases morbidity and mortality rates. Early
      detection and prevention of this complication are very important. A novel
      biomarker named neutrophil gelatinase-associated lipocalin (NGAL) can play an
      important role in early diagnosis of acute kidney injury. Recent studies on the
      favourable effects of Dexmedetomidine on cardiac surgery have been published. The
      aim of this study is to investigate whether there is a dose-dependent positive
      effect of Dexmedetomidine on neutrophil gelatinase-associated lipocalin levels
      and renal functions when used after CABG. METHODS: Our randomized, triple
      blinded, placebo-controlled study was conducted among 295 patients scheduled for
      CABG surgery between August 2009 and March 2011 in a tertiary cardiac and
      vascular surgery clinic. A total of 90 consecutive patients who met inclusion
      criteria were randomized and divided into three groups. The first group received
      a placebo. The second and the third groups received 4 and 8 ug/cc concentration
      of the Dexmedetomidine infusion, respectively. Infusion rates were regulated to
      obtain sedation with a Ramsey sedation score of 2 or 3. Patients were regrouped
      according to the total Dexmedetomidine dose. Statistical analyses of variables
      including serum neutrophil gelatinase-associated lipocalin values and
      conventional renal function tests were made for all six possibilities before the
      blind was broken. RESULTS: Results of conventional renal function tests were not
      significantly different. However, neutrophil gelatinase-associated lipocalin
      levels for the first postoperative day for placebo, low-dose and high-dose
      Dexmedetomidine groups were 176.8 +/- 145.9, 97.7 +/- 63.4 and 67.3 +/- 10.9
      ng/ml, respectively. These values were significantly different among the groups
      (P <0.001). CONCLUSIONS: In our study, we found that Dexmedetomidine infusion for
      sedation after CABG under cardiopulmonary bypass can be useful in the prevention
      of kidney injury. Conventional renal function tests, including blood urea
      nitrogen, serum creatinine, urine output and creatinine clearance rate
      measurements typically may not detect the development of acute kidney dysfunction
      in the first 48-h postoperative period. Differences were detected in renal
      function in the early postoperative period and the development of acute kidney
      injury, as determined by measurements of blood NGAL levels, was significant and
      dose-dependent.

PMID- 25392342
TI  - Mutational studies on resurrected ancestral proteins reveal conservation of site
      specific amino acid preferences throughout evolutionary history.
AB  - Local protein interactions ("molecular context" effects) dictate amino acid
      replacements and can be described in terms of site-specific, energetic
      preferences for any different amino acid. It has been recently debated whether
      these preferences remain approximately constant during evolution or whether, due
      to coevolution of sites, they change strongly. Such research highlights an
      unresolved and fundamental issue with far-reaching implications for phylogenetic
      analysis and molecular evolution modeling. Here, we take advantage of the recent
      availability of phenotypically supported laboratory resurrections of Precambrian
      thioredoxins and beta-lactamases to experimentally address the change of site
      specific amino acid preferences over long geological timescales. Extensive
      mutational analyses support the notion that evolutionary adjustment to a new
      amino acid may occur, but to a large extent this is insufficient to erase the
      primitive preference for amino acid replacements. Generally, site-specific amino
      acid preferences appear to remain conserved throughout evolutionary history
      despite local sequence divergence. We show such preference conservation to be
      readily understandable in molecular terms and we provide crystallographic
      evidence for an intriguing structural-switch mechanism: Energetic preference for
      an ancestral amino acid in a modern protein can be linked to reorganization upon
      mutation to the ancestral local structure around the mutated site. Finally, we
      point out that site-specific preference conservation naturally leads to one
      plausible evolutionary explanation for the existence of intragenic global
      suppressor mutations. 

PMID- 25392343
TI  - In search of beneficial coding RNA editing.
AB  - RNA editing is a posttranscriptional modification that can lead to a change in
      the encoded protein sequence of a gene. Although a few cases of mammalian coding
      RNA editing are known to be functionally important, the vast majority of over
      2,000 A-to-I editing sites that have been identified from the coding regions of
      the human genome are likely nonadaptive, representing tolerable promiscuous
      targeting of editing enzymes. Finding the potentially tiny fraction of beneficial
      editing sites from the sea of mostly nearly neutral editing is a difficult but
      important task. Here, we propose and provide evidence that evolutionarily
      conserved or "hardwired" residues that experience high-level nonsynonymous RNA
      editing in a species are enriched with beneficial editing. This simple approach
      allows the prediction of sites where RNA editing is functionally important. We
      suggest that priority be given to these candidates in future characterizations of
      the functional and fitness consequences of RNA editing. 

PMID- 25392344
TI  - The use of chaperones in general practice: Is this just a 'Western' concept?
AB  - BACKGROUND: The literature about medical chaperones in primary care is limited to
      a handful of English-speaking countries. It remains largely unknown to what
      extent chaperones are offered (and used) outside the published literature.
      OBJECTIVE: The current study aimed to explore the attitudes and experiences of a
      group of general practitioners (GPs; family doctors) attending an international
      primary care conference regarding their use of medical chaperones. METHODS:
      Ninety international GPs completed a validated questionnaire, providing
      information on their current practice, availability and preferred choice of
      chaperone. Participants expressed their opinion on the importance of, and
      facilitators and barriers for chaperone use. RESULTS: Although most participants
      had knowledge of the term 'medical chaperone' (75%), those with a qualification
      from Europe (other than the UK) were less likely to offer a chaperone. Two-thirds
      of all participants would consider offering a chaperone and were more likely to
      work in the public sector (p = .04; Cramer's V = 0.27). A practice nurse was most
      commonly used as chaperone. Chaperone users ranked the 'medico-legal protection
      of doctors', 'doctors' professional practice' and 'protection of patients' as the
      most important factors for using a chaperone. Non-users reported 'personal choice
      of the doctor', 'confidentiality' and 'impact on the doctor-patient relationship'
      as the main areas influencing their decision not to use a chaperone. CONCLUSION:
      International doctors hold different views about the use (or not) of chaperones
      within their clinical practice and its effect on the doctor-patient consultation.
      Further research is needed to tease out the reasons for this.

PMID- 25392345
TI  - The efficacy of antioxidant therapy against oxidative stress and androgen rise in
      ethylene glycol induced nephrolithiasis in Wistar rats.
AB  - Administration of natural antioxidants has been used to protect against
      nephrolithiasis. Urolithiasis was induced by ethylene glycol (EG) in Wistar rats.
      For 4 weeks, group 1 (control) was fed with a standard commercial diet. Group 2
      received the same diet with 0.75% of EG. Group 3 received EG plus the diet and
      water added with antioxidant nutrients and lime juice as the dietary source of
      citrate (EG + AX). Group 4 same as group 3 with no EG in water. For 8 weeks,
      group 5 was fed the standard diet with EG in water for the first 28 days,
      followed by no EG. Group 6 received the diet with EG for the first 28 days,
      followed by discontinuation of EG and addition of antioxidant nutrients. Group 7
      were provided the diet with antioxidant nutrients for 8 weeks. Group 8 received
      the diet with antioxidant nutrients for 4 weeks, followed by antioxidant
      nutrients with EG for the next 4 weeks. Blood samples were collected and kidneys
      were removed. The size and the mean number of crystal deposits in EG-treated
      groups was significantly higher than the EG-treated groups, added with
      antioxidant nutrients and lime juice. After 4 weeks, the mean concentration of
      malondialdehyde in group 2 was higher than the group 3, and significantly lower
      in group 4; and in groups 7 after 8 weeks, as well. After 8 weeks,
      supplementation developed less mean number of deposits in group 6 as compared to
      group 5; and in group 8, the crystal deposits was substantially less than either
      group 2 or group 5 (EG-treated rats). Elevated concentration of androgens (as
      promoters of the formation of renal calculi) as a result of EG consumption
      decreased following antioxidant supplementations. Results showed a beneficial
      effect of antioxidant and provided superior renal protection on treating and
      preventing stone deposition in the rat kidney. 

PMID- 25392347
TI  - Gilvimarinus polysaccharolyticus sp. nov., an agar-digesting bacterium isolated
      from seaweed, and emended description of the genus Gilvimarinus.
AB  - A taxonomic study was carried out on strain YN3(T), which was isolated from a
      seaweed sample taken from the coast of Weihai, China. The bacterium was Gram
      stain-negative, rod-shaped, and could grow at pH 5.0-10.0 and 4-32  degrees C in
      the presence of 0-9.0 % (w/v) NaCl. Strain YN3(T) was positive for the hydrolysis
      of polysaccharides, such as agar, starch and xylan. The predominant respiratory
      quinone was ubiquinone-8. The major fatty acids were C16 : 1omega7c and/or iso
      C15 : 0 2-OH, C16 : 0 and C18 : 1omega7c. The main polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, and
      two unidentified glycolipids. The genomic DNA G+C content was 49.4 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain
      YN3(T) should be assigned to the genus Gilvimarinus. 'Gilvimarinus agarilyticus'
      KCTC 23325 and Gilvimarinus chinensis QM42(T) had the closest phylogenetic
      relationship to strain YN3(T), and showed 97.9 % and 95.8 % sequence
      similarities, respectively. On the basis of phenotypic, chemotaxonomic and
      genotypic data and DNA-DNA hybridization studies, we propose that strain YN3(T)
      represents a novel species of the genus Gilvimarinus, for which the name
      Gilvimarinus polysaccharolyticus sp. nov. is proposed. The type strain is YN3(T)
      ( = KCTC 32438(T) = JCM 19198(T)). An emended description of the genus
      Gilvimarinus is also presented.

PMID- 25392346
TI  - The TWEAK Receptor Fn14 Is an Src-Inducible Protein and a Positive Regulator of
      Src-Driven Cell Invasion.
AB  - The TNF receptor superfamily member Fn14 (TNFRSF12A) is the sole signaling
      receptor for the proinflammatory cytokine TWEAK (TNFSF12). TWEAK: Fn14 engagement
      stimulates multiple signal transduction pathways, including the NF-kappaB
      pathway, and this triggers important cellular processes (e.g., growth,
      differentiation, migration, and invasion). The TWEAK-Fn14 axis is thought to be a
      major physiologic mediator of tissue repair after acute injury. Various studies
      have revealed that Fn14 is highly expressed in many solid tumor types, and that
      Fn14 signaling may play a role in tumor growth and metastasis. Previously, it was
      shown that Fn14 levels are frequently elevated in non-small cell lung cancer
      (NSCLC) tumors and cell lines that exhibit constitutive EGFR phosphorylation
      (activation). Furthermore, elevated Fn14 levels increased NSCLC cell invasion in
      vitro and lung metastatic tumor colonization in vivo. The present study reveals
      that EGFR-mutant NSCLC cells that express high levels of Fn14 exhibit
      constitutive activation of the cytoplasmic tyrosine kinase Src, and that
      treatment with the Src family kinase (SFK) inhibitor dasatinib decreases Fn14
      gene expression at both the mRNA and protein levels. Importantly, siRNA-mediated
      depletion of the SFK member Src in NSCLC cells also decreases Fn14 expression.
      Finally, expression of the constitutively active v-Src oncoprotein in NIH 3T3
      cells induces Fn14 gene expression, and NIH 3T3/v-Src cells require Fn14
      expression for full invasive capacity. IMPLICATIONS: These results indicate that
      oncogenic Src may contribute to Fn14 overexpression in solid tumors, and that Src
      mediated cell invasion could potentially be inhibited with Fn14-targeted
      therapeutics.

PMID- 25392348
TI  - Proposal to rename Carnobacterium inhibens as Carnobacterium inhibens subsp.
      inhibens subsp. nov. and description of Carnobacterium inhibens subsp.
      gilichinskyi subsp. nov., a psychrotolerant bacterium isolated from Siberian
      permafrost.
AB  - A novel, psychrotolerant facultative anaerobe, strain WN1359(T), was isolated
      from a permafrost borehole sample collected at the right bank of the Kolyma River
      in Siberia, Russia. Gram-positive-staining, non-motile, rod-shaped cells were
      observed with sizes of 1-2 um long and 0.4-0.5 um wide. Growth occurred in the
      range of pH 5.8-9.0 with optimal growth at pH 7.8-8.6 (pH optimum 8.2). The novel
      isolate grew at temperatures from 0-37  degrees C and optimal growth occurred at
      25  degrees C. The novel isolate does not require NaCl; growth was observed
      between 0 and 8.8 % (1.5 M) NaCl with optimal growth at 0.5 % (w/v) NaCl. The
      isolate was a catalase-negative, facultatively anaerobic chemo-organoheterotroph
      that used sugars but not several single amino acids or dipeptides as substrates.
      The major metabolic end-product was lactic acid in the ratio of 86 % l-lactate :
      14 % d-lactate. Strain WN1359(T) was sensitive to ampicillin, chloramphenicol,
      fusidic acid, lincomycin, monocycline, rifampicin, rifamycin SV, spectinomycin,
      streptomycin, troleandomycin and vancomycin, and resistant to nalidixic acid and
      aztreonam. The fatty acid content was predominantly unsaturated (70.2 %),
      branched-chain unsaturated (11.7 %) and saturated (12.5 %). The DNA G+C content
      was 35.3 mol% by whole genome sequence analysis. 16S rRNA gene sequence analysis
      showed 98.7 % sequence identity between strain WN1359(T) and Carnobacterium
      inhibens. Genome relatedness was computed using both Genome-to-Genome Distance
      Analysis (GGDA) and Average Nucleotide Identity (ANI), which both strongly
      supported strain WN1359(T) belonging to the species C. inhibens. On the basis of
      these results, the permafrost isolate WN1359(T) represents a novel subspecies of
      C. inhibens, for which the name Carnobacterium inhibens subsp. gilichinskyi
      subsp. nov. is proposed. The type strain is WN1359(T) ( = ATCC BAA-2557(T) = DSM
      27470(T)). The subspecies Carnobacterium inhibens subsp. inhibens subsp. nov. is
      created automatically. An emended description of C. inhibens is also provided.

PMID- 25392349
TI  - Kocuria rhizophila misidentified as Corynebacterium jeikeium and other errors
      caused by the Vitek MS system call for maintained microbiological competence in
      the era of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry.

PMID- 25392350
TI  - Characterization of alpha-toxin hla gene variants, alpha-toxin expression levels,
      and levels of antibody to alpha-toxin in hemodialysis and postsurgical patients
      with Staphylococcus aureus bacteremia.
AB  - Alpha-toxin is a major Staphylococcus aureus virulence factor. This study
      evaluated potential relationships between in vitro alpha-toxin expression of S.
      aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with
      S. aureus bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100
      postsurgical SAB patients. Isolates underwent spa typing and hla sequencing.
      Serum anti-alpha-toxin IgG and neutralizing antibody levels were measured by
      using an enzyme-linked immunosorbent assay and a red blood cell (RBC)-based
      hemolysis neutralization assay. Neutralization of alpha-toxin by an anti-alpha
      toxin monoclonal antibody (MAb MEDI4893) was tested in an RBC-based lysis assay.
      Most isolates encoded hla (197/200; 98.5%) and expressed alpha-toxin (173/200;
      86.5%). In vitro alpha-toxin levels were inversely associated with survival
      (cure, 2.19 MUg/ml, versus failure, 1.09 MUg/ml; P < 0.01). Both neutralizing
      (hemodialysis, 1.26 IU/ml, versus postsurgical, 0.95; P < 0.05) and IgG
      (hemodialysis, 1.94 IU/ml, versus postsurgical, 1.27; P < 0.05) antibody levels
      were higher in the hemodialysis population. Antibody levels were also
      significantly higher in patients infected with alpha-toxin-expressing S. aureus
      isolates (P < 0.05). Levels of both neutralizing antibodies and IgG were similar
      among patients who were cured and those not cured (failures). Sequence analysis
      of hla revealed 12 distinct hla genotypes, and all genotypic variants were
      susceptible to a neutralizing monoclonal antibody in clinical development
      (MEDI4893). These data demonstrate that alpha-toxin is highly conserved in
      clinical S. aureus isolates. Higher in vitro alpha-toxin levels were associated
      with a positive clinical outcome. Although patients infected with alpha-toxin
      producing S. aureus exhibited higher anti-alpha-toxin antibody levels, these
      levels were not associated with a better clinical outcome in this study. 

PMID- 25392351
TI  - Evaluation of the Aspergillus Western blot IgG kit for diagnosis of chronic
      aspergillosis.
AB  - Immunoprecipitin detection (IPD) is the current reference confirmatory technique
      for anti-Aspergillus antibody detection; however, the lack of standardization is
      a critical drawback of this assay. In this study, we evaluated the performance of
      the Aspergillus Western blot (Asp-WB) IgG kit (LDBio Diagnostics, Lyon, France),
      a recently commercialized immunoblot assay for the diagnosis of various clinical
      presentations of chronic aspergillosis. Three hundred eight serum samples from
      158 patients with aspergillosis sensu lato (s.l.) were analyzed. More
      specifically, 267 serum samples were derived from patients with Aspergillus
      disease, including 89 cases of chronic pulmonary aspergillosis, 10 of
      aspergilloma, and 32 of allergic bronchopulmonary aspergillosis, while 41 samples
      were from patients with Aspergillus colonization, including 15 cystic fibrosis
      (CF) and 12 non-CF patients. For blood donor controls, the Asp-WB specificity was
      94%, while the kit displayed a sensitivity for the aspergillosis s.l. diagnosis
      of 88.6%, with a diagnostic odds ratio (DOR) of 119 (95% confidence interval
      [CI], 57 to 251). The DOR values were 185.22 (95% CI,78.79 to 435.45) and 43.74
      (95% CI, 15.65 to 122.20) for the diagnosis of Aspergillus disease and
      Aspergillus colonization, respectively. Among the patients, the sensitivities of
      the Asp-WB in the diagnosis of Aspergillus colonization were 100% and 41.7% in CF
      and non-CF patients, respectively. The Asp-WB yielded fewer false-negative
      results than did IPD. In conclusion, the Asp-WB kit performed well for the
      diagnosis of various clinical presentations of aspergillosis in
      nonimmunocompromised patients, with an enhanced standardization and a higher
      sensitivity than with IPD, which is the current reference method. 

PMID- 25392352
TI  - Comparative evaluation of a new commercial colorimetric microdilution assay
      (SensiQuattro Candida EU) with MIC test strip and EUCAST broth microdilution
      methods for susceptibility testing of invasive Candida isolates.
AB  - Candidemia is an important cause of morbidity and mortality in immunosuppressed
      patients. Candida isolates must be cultivated, identified, and tested for
      susceptibility. We compared the performance of a new colorimetric broth
      microdilution panel (SensiQuattro Candida EU) for antifungal susceptibility
      testing to that of Liofilchem's MIC test strip and the EUCAST reference broth
      microdilution protocol. We tested 187 blood culture isolates of 5 Candida spp.
      (120 C. albicans, 38 C. glabrata, 10 C. parapsilosis, 12 C. tropicalis, and 7 C.
      krusei) against seven antifungal agents (amphotericin B, fluconazole,
      voriconazole, posaconazole, caspofungin, anidulafungin, and micafungin) and
      interpreted the MICs according to the EUCAST recommendations. If applicable, the
      overall essential agreement (EA) of the SensiQuattro panel with the reference
      broth microdilution was slightly higher for C. albicans (87%) than for other
      species (85.8%). We found that SensiQuattro performed best in testing
      amphotericin B (EA, 100%), voriconazole (EA, 93.7%), and posaconazole (EA, 94.8%)
      against C. albicans, but its error rate for this species was high (29.6%) because
      of mainly major errors (26.7%) in testing anidulafungin and micafungin. Compared
      to the SensiQuattro panel, the MIC test strip exhibited a higher level of
      agreement for most isolates. SensiQuattro assays are easy to perform, but they
      are currently not suitable for testing echinocandins against Candida spp. 

PMID- 25392353
TI  - Bartonella clarridgeiae bacteremia detected in an asymptomatic blood donor.
AB  - Human exposure to Bartonella clarridgeiae has been reported only on the basis of
      antibody detection. We report for the first time an asymptomatic human blood
      donor infected with B. clarridgeiae, as documented by enrichment blood culture,
      PCR, and DNA sequencing. 

PMID- 25392354
TI  - Whole-genome sequencing confirms that Burkholderia pseudomallei multilocus
      sequence types common to both Cambodia and Australia are due to homoplasy.
AB  - Burkholderia pseudomallei isolates with shared multilocus sequence types (STs)
      have not been isolated from different continents. We identified two STs shared
      between Australia and Cambodia. Whole-genome analysis revealed substantial
      diversity within STs, correctly identified the Asian or Australian origin, and
      confirmed that these shared STs were due to homoplasy. 

PMID- 25392356
TI  - Development of an immunochromatographic assay kit using fluorescent silica
      nanoparticles for rapid diagnosis of Acanthamoeba keratitis.
AB  - We developed an immunochromatographic assay kit that uses fluorescent silica
      nanoparticles bound to anti-Acanthamoeba antibodies (fluorescent
      immunochromatographic assay [FICGA]) and evaluated its efficacy for the detection
      of Acanthamoeba and diagnosis of Acanthamoeba keratitis (AK). The sensitivity of
      the FICGA kit was evaluated using samples of Acanthamoeba trophozoites and cysts
      diluted to various concentrations. A conventional immunochromatographic assay kit
      with latex labels (LICGA) was also evaluated to determine its sensitivity in
      detecting Acanthamoeba trophozoites. To check for cross-reactivity, the FICGA was
      performed by using samples of other common causative pathogens of infectious
      keratitis, such as Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus
      epidermidis, and Candida albicans. Corneal scrapings from patients with suspected
      AK were tested with the FICGA kit to detect the presence of Acanthamoeba, and the
      results were compared with those of real-time PCR. The FICGA kit detected
      organisms at concentrations as low as 5 trophozoites or 40 cysts per sample.
      There were no cross-reactivities with other pathogens. The FICGA was
      approximately 20 times more sensitive than the LICGA for the detection of
      Acanthamoeba trophozoites. The FICGA kit yielded positive results for all 10
      patients, which corresponded well with the real-time PCR results. The FICGA kit
      demonstrated high sensitivity for the detection of Acanthamoeba and may be useful
      for the diagnosis of AK. 

PMID- 25392355
TI  - Evaluation of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry for identification of Vibrio cholerae.
AB  - We evaluated the use of matrix-assisted laser desorption ionization-time of
      flight mass spectrometry (MS) for the identification of Vibrio cholerae. MS
      identified all 42 isolates of V. cholerae O1 and O139 and 7 of 9 non-O1/O139
      isolates. MS correctly discriminated between all Aeromonas and V. cholerae
      isolates. Overall, MS performed as well as or better than biochemical methods. 

PMID- 25392357
TI  - Supplementary testing is not required in the cobas 4800 CT/NG test for Neisseria
      gonorrhoeae weak-positive urogenital samples.
AB  - Weak-positive Neisseria gonorrhoeae nucleic acid amplification test results are
      difficult to interpret. We show that the frequency of unconfirmed N. gonorrhoeae
      results from the cobas 4800 test rises exponentially after 38.0 cycles, where the
      likelihood of an unconfirmed result exceeds 29%. Supplementary testing of such
      samples should be avoided; instead, treatment should be based on clinical pretest
      probability. 

PMID- 25392358
TI  - Genomic signature of multidrug-resistant Salmonella enterica serovar typhi
      isolates related to a massive outbreak in Zambia between 2010 and 2012.
AB  - Retrospectively, we investigated the epidemiology of a massive Salmonella
      enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four
      isolates were susceptibility tested by MIC determinations. Whole-genome sequence
      typing (WGST) of 33 isolates and bioinformatic analysis identified the multilocus
      sequence type (MLST), haplotype, plasmid replicon, antimicrobial resistance
      genes, and genetic relatedness by single nucleotide polymorphism (SNP) analysis
      and genomic deletions. The outbreak affected 2,040 patients, with a fatality rate
      of 0.5%. Most (83.0%) isolates were multidrug resistant (MDR). The isolates
      belonged to MLST ST1 and a new variant of the haplotype, H58B. Most isolates
      contained a chromosomally translocated region containing seven antimicrobial
      resistance genes, catA1, blaTEM-1, dfrA7, sul1, sul2, strA, and strB, and
      fragments of the incompatibility group Q1 (IncQ1) plasmid replicon, the class 1
      integron, and the mer operon. The genomic analysis revealed 415 SNP differences
      overall and 35 deletions among 33 of the isolates subjected to whole-genome
      sequencing. In comparison with other genomes of H58, the Zambian isolates
      separated from genomes from Central Africa and India by 34 and 52 SNPs,
      respectively. The phylogenetic analysis indicates that 32 of the 33 isolates
      sequenced belonged to a tight clonal group distinct from other H58 genomes
      included in the study. The small numbers of SNPs identified within this group are
      consistent with the short-term transmission that can be expected over a period of
      2 years. The phylogenetic analysis and deletions suggest that a single MDR clone
      was responsible for the outbreak, during which occasional other S. Typhi
      lineages, including sensitive ones, continued to cocirculate. The common view is
      that the emerging global S. Typhi haplotype, H58B, containing the MDR IncHI1
      plasmid is responsible for the majority of typhoid infections in Asia and sub
      Saharan Africa; we found that a new variant of the haplotype harboring a
      chromosomally translocated region containing the MDR islands of IncHI1 plasmid
      has emerged in Zambia. This could change the perception of the term "classical
      MDR typhoid" currently being solely associated with the IncHI1 plasmid. It might
      be more common than presently thought that S. Typhi haplotype H58B harbors the
      IncHI1 plasmid or a chromosomally translocated MDR region or both. 

PMID- 25392359
TI  - A taxonomically unique Acinetobacter strain with proteolytic and hemolytic
      activities recovered from a patient with a soft tissue injury.
AB  - A taxonomically unique bacterial strain, Acinetobacter sp. A47, has been
      recovered from several soft tissue samples from a patient undergoing
      reconstructive surgery owing to a traumatic amputation. The results of 16S rRNA,
      rpoB, and gyrB gene comparative sequence analyses showed that A47 does not belong
      to any of the hitherto-known taxa and may represent an as-yet-unknown
      Acinetobacter species. The recognition of this novel organism contributes to our
      knowledge of the taxonomic complexity underlying infections caused by
      Acinetobacter. 

PMID- 25392360
TI  - Comparison of GenomEra C. difficile and Xpert C. difficile as confirmatory tests
      in a multistep algorithm for diagnosis of Clostridium difficile infection.
AB  - We compared two multistep diagnostic algorithms based on C. Diff Quik Chek
      Complete and, as confirmatory tests, GenomEra C. difficile and Xpert C.
      difficile. The sensitivity, specificity, positive predictive value, and negative
      predictive value were 87.2%, 99.7%, 97.1%, and 98.3%, respectively, for the
      GenomEra-based algorithm and 89.7%, 99.4%, 95.5%, and 98.6%, respectively, for
      the Xpert-based algorithm. GenomEra represents an alternative to Xpert as a
      confirmatory test of a multistep algorithm for Clostridium difficile infection
      (CDI) diagnosis. 

PMID- 25392361
TI  - Analysis of changes in diversity and abundance of the microbial community in a
      cystic fibrosis patient over a multiyear period.
AB  - The evolution of pulmonary disease in cystic fibrosis (CF) usually begins when
      bacteria get trapped in mucus in the lungs and become established as a chronic
      infection. While most CF patients experience periods of stability, pulmonary
      exacerbations (PEs) can occur multiple times per year and result in permanent
      damage to the lungs. Little is known of the shift from a period of stability to a
      PE, but this shift is likely to be attributed to changes in the bacterial
      community. Here, we identified changes in the lung microbiota to determine if
      they reflect patient health, indicate the onset of exacerbations, or are related
      to antibiotic treatment. In contrast to most bacterial studies on CF, we
      collected weekly samples from an adult CF patient over a period of 3 years and
      performed quantitative PCR (qPCR) and Illumina sequencing on those samples. While
      many DNA-based studies have shown the CF microbiota to be relatively stable, we
      observed an increase in the total bacterial abundance over time (P < 0.001),
      while the number of different taxa (bacterial richness) and the number of
      different taxa and their abundances (diversity) significantly decreased over time
      (P < 0.03), which was likely due to repeated antibiotic exposure. Using genus
      specific primers with qPCR, we observed an increase in the abundance of
      Burkholderia multivorans, a CF-associated pathogen, prior to the occurrence of a
      PE (P = 0.006). Combining these DNA-based techniques with frequent sampling
      identified a potential initiator for exacerbations and described a response of
      the CF microbiota to time and antibiotic treatment not observed in previous CF
      microbiota studies. 

PMID- 25392362
TI  - Ebola virus: a clear and present danger.
AB  - An epidemic of Ebola virus disease is occurring in Western Africa on a scale not
      seen before, particularly in the countries of Guinea, Liberia, and Sierra Leone.
      The continued spread is facilitated by insufficient medical facilities, poor
      sanitation, travel, and unsafe burial practices. Several patients diagnosed with
      Ebola virus disease in Africa have been evacuated to the United States for
      treatment, and several other patients have been diagnosed in the United States.
      It is important for laboratories to be aware of available tests, especially those
      granted emergency use authorization, as hospitals prepare protocols for the
      diagnosis and management of high-risk patients. 

PMID- 25392363
TI  - Does sequence type 33 of Shiga toxin-producing Escherichia coli O91 cause only
      mild symptoms?

PMID- 25392364
TI  - Evaluation of an online program to teach microbiology to internal medicine
      residents.
AB  - Microbiology rounds are an integral part of infectious disease consultation
      service. During microbiology rounds, we highlight microbiology principles using
      vignettes. We created case-based, interactive, microbiology online modules
      similar to the vignettes presented during microbiology rounds. Since internal
      medicine residents rotating on our infectious disease elective have limited time
      to participate in rounds and learn microbiology, our objective was to evaluate
      the use of the microbiology online modules by internal medicine residents. We
      asked residents to complete 10 of 25 online modules during their infectious
      disease elective. We evaluated which modules they chose and the change in their
      knowledge level. Forty-six internal medicine residents completed assessments
      given before and after accessing the modules with an average of 11/20 (range, 6
      to 19) and 16/20 (range, 9 to 20) correct questions, respectively (average
      improvement, 5 questions; P = 0.0001). The modules accessed by more than 30
      residents included those related to Clostridium difficile, anaerobes, Candida
      spp., Streptococcus pneumoniae, influenza, Mycobacterium tuberculosis, and
      Neisseria meningitidis. We demonstrated improved microbiology knowledge after
      completion of the online modules. This improvement may not be solely attributed
      to completing the online modules, as fellows and faculty may have provided
      additional microbiology education during the rotation. 

PMID- 25392366
TI  - A happy birthday and a transition at the Journal of Clinical Microbiology.

PMID- 25392365
TI  - Standardization of Nucleic Acid Tests for Clinical Measurements of Bacteria and
      Viruses.
AB  - Nucleic acid-based tests for infectious diseases currently used in the clinical
      laboratory and in point-of-care devices are diverse. Measurement challenges
      associated with standardization of quantitative viral load testing are discussed
      in relation to human cytomegalovirus, BK virus, and Epstein-Barr virus, while the
      importance of defining the performance of qualitative methods is illustrated with
      Mycobacterium tuberculosis and influenza virus. The development of certified
      reference materials whose values are traceable to higher-order standards and
      reference measurement procedures, using, for instance, digital PCR, will further
      contribute to the understanding of analytical performance characteristics and
      promote clinical data comparability. 

PMID- 25392367
TI  - RESPOND: a patient-centred programme to prevent secondary falls in older people
      presenting to the emergency department with a fall-protocol for a mixed methods
      programme evaluation.
AB  - BACKGROUND: Programme evaluations conducted alongside randomised controlled
      trials (RCTs) have potential to enhance understanding of trial outcomes. This
      paper describes a multi-level programme evaluation to be conducted alongside an
      RCT of a falls prevention programme (RESPOND). OBJECTIVES: (1) To conduct a
      process evaluation in order to identify the degree of implementation fidelity and
      associated barriers and facilitators. (2) To evaluate the primary intended impact
      of the programme: participation in fall prevention strategies and the factors
      influencing participation. (3) To identify the factors influencing RESPOND RCT
      outcomes: falls, fall injuries and emergency department (ED) re-presentations.
      METHODS/DESIGN: 528 community-dwelling adults aged 60-90 years presenting to two
      EDs with a fall will be recruited and randomly assigned to the intervention or
      standard care group. All RESPOND participants and RESPOND clinicians will be
      included in the evaluation. A mixed methods design will be used and a programme
      logic model will frame the evaluation. Data will be sourced from interviews,
      focus groups, questionnaires, clinician case notes, recruitment records,
      participant-completed calendars, hospital administrative datasets and audio
      recordings of intervention contacts. Quantitative data will be analysed via
      descriptive and inferential statistics and qualitative data will be interpreted
      using thematic analysis. DISCUSSION: The RESPOND programme evaluation will
      provide information about contextual and influencing factors related to the
      RESPOND RCT outcomes. The results will assist researchers, clinicians and policy
      makers regarding decisions about future falls prevention interventions. Insights
      gained may be applicable to a range of chronic conditions where similar
      preventive intervention approaches are indicated. TRIAL REGISTRATION NUMBER: This
      programme evaluation is linked to the RESPOND RCT which is registered with the
      Australian New Zealand Clinical Trials Registry (ACTRN12614000336684).

PMID- 25392368
TI  - A simple tragedy with a special resonance.

PMID- 25392369
TI  - Knowledge, attitudes, experience and behaviour of frontline health care workers
      during the early phase of 2009 influenza A(H1N1) pandemic, Birmingham, UK.
AB  - OBJECTIVES: During the early ('containment') phase of the influenza A(H1N1)
      pandemic, when the severity of the pandemic was unclear, health care workers
      (HCWs) across the UK were deployed to swab and prescribe antiviral drugs to
      suspected cases. This study describes the knowledge, attitudes, experience and
      behaviour of frontline HCWs in Birmingham, West Midlands, during this period.
      METHODS: During June 2009, a 25-item semi-structured questionnaire was used to
      survey HCWs who undertook defined clinical duties as part of the public health
      response during the early phase of the pandemic. Participants were clinical staff
      based in a primary care out-of-hours service provider. RESULTS: The response rate
      was 50% (n = 20). All respondents provided direct clinical care that necessitated
      prolonged close contact with potentially infectious cases. Knowledge and use of
      personal protective equipment and infection control procedures was consistently
      high. However, the main source of infection control advice was local guidance.
      Uptake of, and attitude towards, vaccination as a preventive measure and
      antiviral prophylaxis was poor. CONCLUSIONS: HCWs were prepared to provide an
      essential health care response during the pandemic even when the severity of
      disease was unclear. However, more needs to be done to change health care
      workers' negative attitudes towards taking antivirals and receiving influenza
      vaccination.

PMID- 25392373
TI  - Intimate Partner Victimization Among College Students With and Without
      Disabilities: Prevalence of and Relationship to Emotional Well-Being.
AB  - Prior research indicates that both college students and individuals with
      disabilities are at an increased risk of experiencing intimate partner
      victimization (IPV). However, little is known about IPV risk and its relationship
      to emotional well-being among the intersection of these two populations.
      Utilizing a sample of approximately 20,000 college students from the American
      College Health Association's (ACHA) National College Health Assessment II (NCHA
      II), this study focuses on this overlooked intersection by examining IPV among
      college students with disabilities. Multivariate binary logistic regression
      models were used to estimate the relationship among disability, IPV, and
      emotional well-being. College students with disabilities were approximately twice
      as likely to experience IPV than their counterparts without disabilities.
      Students with mental disabilities and multiple disability types were found to
      have the greatest likelihood of experiencing IPV. Victims with disabilities were
      more likely than victims without disabilities to report experiencing depression
      symptoms, self-harm behavior, and stress. Recommendations for reducing and
      preventing IPV among a college student population are discussed. 

PMID- 25392370
TI  - Tumor-penetrating iRGD peptide inhibits metastasis.
AB  - Tumor-specific tissue-penetrating peptides deliver drugs into extravascular tumor
      tissue by increasing tumor vascular permeability through interaction with
      neuropilin (NRP). Here, we report that a prototypic tumor-penetrating peptide
      iRGD (amino acid sequence: CRGDKGPDC) potently inhibits spontaneous metastasis in
      mice. The antimetastatic effect was mediated by the NRP-binding RXXK peptide
      motif (CendR motif), and not by the integrin-binding RGD motif. iRGD inhibited
      migration of tumor cells and caused chemorepulsion in vitro in a CendR- and NRP-1
      dependent manner. The peptide induced dramatic collapse of cellular processes and
      partial cell detachment, resulting in the repellent activity. These effects were
      prominently displayed when the cells were seeded on fibronectin, suggesting a
      role of CendR in functional regulation of integrins. The antimetastatic activity
      of iRGD may provide a significant additional benefit when this peptide is used
      for drug delivery to tumors.

PMID- 25392374
TI  - Accounting for Intimate Partner Violence: A Biographical Analysis of Narrative
      Strategies Used by Men Experiencing IPV From Their Female Partners.
AB  - Intimate partner violence (IPV) is a serious social issue which affects the
      medium- and long-term health outcomes of many individuals worldwide. The cost of
      IPV on the physical and psychological well-being of individuals, in addition to
      its wider economic costs in responding to abused persons, is significant.
      Presently, there is a lack of understanding about the nature of female-initiated
      IPV and how men account for their experiences of it. This study examined male
      victims' life stories of their IPV experiences from their intimate partners.
      Using the biographical narrative interpretive method, three cases were analyzed
      from a social constructionist perspective to examine what narrative strategies
      men used to account for their experiences of being abused by their female
      partners. Three dominant narrative strategies were used by respondents: the
      fatherhood narrative, the good husband narrative, and the abuse narrative. The
      abuse narrative had a unique narrative form, which reflected respondents'
      disassociation between their identities as men and also as abused persons.
      Dominant conflicting discourses of masculinity and intimate partner abuse
      disadvantaged men in identifying IPV and secondly in responding appropriately.
      This study found that men prefer to use dominant discursive identities as
      legitimate means from which to disclose IPV experiences. The findings from this
      study illustrate that broad questioning by professionals regarding fatherhood may
      be most helpful in promoting disclosures of IPV if this is suspected. 

PMID- 25392375
TI  - The Feto-Maternal Health Cost of Intimate Partner Violence Among Delivery-Related
      Discharges in the United States, 2002-2009.
AB  - Our purpose was to estimate the national prevalence of intimate partner violence
      (IPV) among delivery-related discharges and to investigate its association with
      adverse feto-maternal birth outcomes and delivery-related cost. A retrospective
      cross-sectional analysis of delivery-related hospital discharges from 2002 to
      2009 was conducted using the Nationwide Inpatient Sample (NIS). We used ICD-9-CM
      codes to identify IPV, covariates, and outcomes. Multivariable logistic
      regression modeling was used to calculate adjusted odds ratios (OR) and 95%
      confidence intervals (CI) for the associations between IPV and each outcome.
      Joinpoint regression was used for trend analysis. During the study period, 3,649
      delivery-related discharges were diagnosed with IPV (11.2 per 100,000; 95% CI =
      [10.0, 12.4]). IPV diagnosis during delivery is associated with stillbirth (AOR =
      4.12, 95% CI = [2.75, 6.17]), preterm birth (AOR = 1.97, 95% CI = [1.59, 2.44]),
      fetal death (AOR = 3.34, 95% CI = [1.99, 5.61]), infant with poor intrauterine
      growth (AOR = 1.55, 95% CI = [1.01, 2.40]), and increased inpatient hospital care
      cost (US$5,438.2 vs. US$4,080.1) per each discharge, incurring an additional cost
      of US$4,955,707 during the study period. IPV occurring during pregnancy has a
      significant health burden to both the mother and infant. Education about IPV;
      screening at periodic intervals, including during obstetric visits; and ongoing
      clinical care could help to reduce or eliminate adverse effects of pregnancy
      related IPV. Preventing the lifelong consequences associated with IPV can have a
      positive effect on the overall health of all women and delivery-related health
      care cost. 

PMID- 25392376
TI  - Protective Informal Social Control of Child Maltreatment and Child Abuse Injury
      in Seoul.
AB  - Previous findings on the relationship between neighborhood informal social
      control and child abuse have been mixed. We implemented a scale created by Emery,
      Trung, and Wu to study protective informal social control of child maltreatment
      (ISC_CM) by neighbors in a three-stage random cluster sample of 541 families in
      Seoul, South Korea. Random-effects regression models found that protective ISC_CM
      significantly moderated the relationship between very severe abuse and child
      injuries. Very severe abuse was associated with fewer injuries when levels of
      protective ISC_CM were higher. Implications are discussed. 

PMID- 25392377
TI  - The Sexual Exploitation of Girls in the United States: The Role of Female Pimps.
AB  - The role of women in the sex trafficking of minors in the United States has
      received limited research attention. Case study analysis of 49 female pimps from
      federal, state, and local cases were analyzed to explore whether there were
      differences in the penalties given to females when compared with their male co
      defendants, and cross-case analysis was conducted to identify themes that
      represent female pimp typologies. Both prison sentence and probation sentences
      were significantly lower for female co-defendants when compared with their male
      co-defendants. Five discrete typologies were developed including Bottom,
      Madam/Business Partner, Family, Girilla, and Handler. Each of these had unique
      features regarding violence toward their minor victims, co-defendants, actions
      during the sexual exploitation of the minor, and sentencing outcomes.
      Implications for practice and future research were recommended. 

PMID- 25392378
TI  - Relations Between Intimate Partner Violence and Forgiveness Among College Women.
AB  - The purpose of the current investigation was to examine forgiveness and intimate
      partner violence (IPV) among college women. Undergraduate women (N = 502)
      participated in an online study in which overall experiences of IPV, as well as
      experiences of psychological and physical IPV, were investigated with respect to
      transgression-specific and dispositional forgiveness. Simultaneous multivariate
      regressions revealed that (a) the experience of IPV was associated with higher
      levels of avoidance and revenge, and lower levels of benevolence, forgiveness of
      self, forgiveness of others, and forgiveness of uncontrollable situations; (b)
      types of IPV demonstrated differing impacts on forgiveness; and (c) the mere
      experience of IPV is more salient than its frequency. 

PMID- 25392379
TI  - The Impact of Specific and Complex Trauma on the Mental Health of Homeless Youth.
AB  - This study investigates the relative impact of trauma experiences that occurred
      prior to and since becoming homeless on depressive symptoms, posttraumatic stress
      disorder (PTSD) symptoms, and self-injurious behaviors among a sample of homeless
      youth (N = 389). Youth (aged 13 to 25) who had been homeless or precariously
      housed in the past year completed a survey about housing history, experiences of
      violence and victimization, mental health, and service utilization. In addition
      to examining the impact associated with specific trauma types, we also considered
      the effect of "early-on" poly-victimization (i.e., cumulative number of reported
      traumas prior to homelessness) and the influence of a compound sexual trauma
      variable created to represent earlier complex trauma. This created-variable has
      values ranging from no reported trauma, single trauma, multiple non-sexual
      traumas, and multiple traumas that co-occurred with sexual abuse. Multivariate
      analyses revealed that specific traumatic experiences prior to homelessness,
      including sexual abuse, emotional abuse/neglect, and adverse home environment,
      predicted greater mental health symptoms. Poly-victimization did not add to the
      prediction of mental health symptoms after the inclusion of specific traumas.
      Results with early compound sexual trauma revealed significant differences
      between lower-order trauma exposures and multiple-trauma exposures. Specifically,
      experience of multiple traumas that co-occurred with sexual trauma was
      significantly more detrimental in predicting PTSD symptoms than multiple traumas
      of non-sexual nature. Findings support the utility of an alternate/novel
      conceptualization of complex trauma, and support the need to carefully evaluate
      complex traumatic experiences that occurred prior to homelessness, which can
      impact the design and implementation of mental health care and services for
      homeless youth. 

PMID- 25392380
TI  - Multiple Forms and Settings of Exposure to Violence and Values: Unique and
      Interactive Relationships With Antisocial Behavior in Adolescence.
AB  - The general purpose of this study was to investigate the relationships between
      multiple forms and settings of exposure to violence (ETV) as well as personal
      values and antisocial behavior (ASB) in adolescence. The association of ETV as
      witness or victim in different contexts (family, school, or neighborhood) and the
      association of the selected values of power, universalism, and conformity with
      ASB were analyzed. In addition, the role of ETV in moderating the relationship
      between values and ASB was tested. A total of 369 adolescents participated in the
      study. Hierarchical multiple regression analysis was performed. Results revealed
      that ASB was independently affected by exposure to family violence as a victim,
      exposure to school violence as a witness, exposure to neighborhood violence as a
      witness, and by all three selected values. The associations of ASB with
      universalism and conformity were negative. Conversely, the association of ASB
      with power was positive. One interaction had statistically significant effects.
      Results revealed that exposure to school violence as a witness moderates the
      relationship between universalism and ASB. The results highlight a high
      percentage of explained variance by ETV and values on ASB and suggest the
      importance of adopting a socio-ecological framework in interpreting adolescent
      behavior. 

PMID- 25392381
TI  - Correlates of Polyvictimization Among African American Youth: An Exploratory
      Study.
AB  - African American adolescents are exposed to high rates of community violence, and
      recent evidence indicates that these youth may also be at high risk of
      polyvictimization. Guided by an ecological approach, this study explored
      individual, familial, and extra-familial correlates of single and multiple forms
      of violence exposures (i.e., witnessing verbal parental aggression, witnessing or
      being a victim of community violence exposures) among a sample of 563 urban
      African American adolescents. Findings indicated that boys reported higher levels
      of polyvictimization than girls. In addition, the correlates of violence
      exposures varied by typology and gender. These findings support the development
      and use of gender-oriented approaches for identifying youth at risk of various
      types of violence exposures. 

PMID- 25392382
TI  - Ethnoracial Variation in Women's Exposure to Intimate Partner Violence.
AB  - While intimate partner violence (IPV) has been acknowledged as a national public
      health concern, little research exists that directly assesses differential
      exposure to IPV for distinct ethnoracial groups. The current study compared the
      rate, severity, and type of IPV exposure across samples of White, African
      American, and Latina women (N = 180). Participants reported rates of exposure to
      violence on measures of physical assault, psychological aggression, injury, and
      sexual coercion; each subscale contained items denoting both mild and severe
      levels of violence. Multiple regression analyses indicated that women's frequency
      of exposure to sexual coercion, and severe and injurious violence significantly
      differed based on participants' ethnoracial identification, such that Latina
      women experienced disproportionate levels of violence relative to White and
      African American peers. Mothers' monthly income, level of education, general
      health, and relationship status also emerged as significant predictors of
      violence exposure. Results support the development of culturally sensitive
      adaptations of IPV interventions, targeting not only Latina populations but also
      women who are single, low-income, and educationally underserved. 

PMID- 25392383
TI  - Exposure to Family Violence, Perceived Psychological Adjustment of Parents, and
      the Development of Post-Traumatic Stress Symptoms Among Palestinian University
      Students.
AB  - The article presents the results of a study on the relationship between exposure
      to (i.e., witnessing and experiencing) different patterns and types of family
      violence during childhood, during adolescence, and during young adulthood, on one
      hand, and adult post-traumatic stress symptoms (PTSS), on the other. A cross
      sectional survey was conducted among 1,969 Palestinian students using a self
      administered questionnaire. The results reveal that the more the participants
      witnessed and experienced psychological aggression (PS) and physical violence
      (PH) in their families of origin, the more they exhibited PTSS. Furthermore, the
      results indicate that a significant amount of the variance in the participants'
      PTSS could be attributed to their exposure to family violence, over and above the
      amounts of variance that were explained by their sociodemographic characteristics
      and by their perceptions of their parents' psychological adjustment. The
      limitations of the study and implications for future research are discussed. 

PMID- 25392384
TI  - Participation in High School Sports and Bystander Intentions, Efficacy to
      Intervene, and Rape Myth Beliefs.
AB  - Debate exists as to whether male athletes are more prone to commit acts of sexual
      violence and maintain problematic attitudes about sexual assault. To contribute
      to the literature on this relationship, this study posed the following research
      questions: (1) Do those students who participated in high school sports and those
      who did not differ significantly in their attitudes about sexual violence and
      willingness to intervene as a bystander? Do these differ among types of rape
      myths and bystander intervention situations? (2) Within a group of athletes, are
      there significant differences by gender or type of sport (contact sport vs. non
      contact?) To answer these questions, surveys were analyzed with a sample of
      recent high school graduates the summer before entering college (N = 3,588).
      Results indicate that there were only minor differences between those students
      who participated in high school varsity sports and those who did not. Students
      who participated in sports had greater acceptance of three out of five types of
      rape myths, and less willingness to intervene with perpetrators after an assault;
      however, the effect sizes were small. There were no significant differences for
      bystander efficacy. The interaction between sport and gender was significant, but
      contact sport was not. The findings suggest that there may be aspects of male
      athletic participation in sports that needs to be addressed, yet there also
      exists the potential for engaging athletes as leaders who can act as prosocial
      bystanders. 

PMID- 25392385
TI  - Hitting Back: Women's Use of Physical Violence Against Violent Male Partners, in
      the Context of a Violent Episode.
AB  - This article explores women's use of physical violence in the context of
      experiencing intimate partner violence (IPV). Data were drawn from the New
      Zealand Violence Against Women Study, a cross-sectional household survey
      conducted using a population-based cluster-sampling scheme. Multinomial logistic
      regression was used to identify factors associated with women's use of physical
      violence against their partners when they were being physically hurt. Of the 843
      women who had experienced physical violence perpetrated by an intimate partner,
      64% reported fighting back at least once or twice whereas 36% never fought back.
      Analyses showed that women's use of violence more than once or twice was
      associated with experience of severe IPV, IPV that had "a lot of effect" on their
      mental health, and with children being present when the woman was being
      physically abused. Women's use of physical violence only once or twice was
      associated with both partners having alcohol problems and both having been
      exposed to violence as a child. Of the women who fought back, 66% reported that
      this did not result in the violence stopping. 

PMID- 25392386
TI  - Intimate Partner Violence and Its Association With Physical and Mental Health
      Symptoms Among Older Women in Germany.
AB  - Intimate partner violence is a commonly acknowledged health care issue. While
      numerous studies established the health implications of physical and/or sexual
      intimate partner violence among women of reproductive age, the evidence is scarce
      for older women and for other forms of intimate partner violence. This study,
      therefore, investigates the prevalence of intimate partner violence in its
      different forms and its association with physical and mental health symptoms of
      older women, using women of reproductive age as a reference group. This study is
      a cross-sectional study, utilizing data from a national representative survey of
      10,264 German women aged 16 to 86 years. Rates of physical and sexual intimate
      partner violence in the last year decreased from 8% to 3% and 1% among women aged
      16 to 49 years, 50 to 65 years, and 66 to 86 years, respectively. The prevalence
      of emotional and economic abuse and controlling behavior by partners remained
      nearly the same. All forms of intimate partner violence had significant
      associations with women's health symptoms, such as gastrointestinal,
      psychosomatic and psychological symptoms, and pelvic problems. Controlling
      behavior was most consistently associated with most health symptoms. Health and
      care professionals who screen women for intimate partner violence should,
      therefore, consider incorporating questions about controlling behavior as well,
      because this form of violence is not only frequent but also has multiple health
      outcomes among women across all ages. 

PMID- 25392387
TI  - International Perceptions of Relational Stalking: The Influence of Prior
      Relationship, Perpetrator Sex, Target Sex, and Participant Sex.
AB  - The present study examines the influence of prior relationship on perceptions of
      relational stalking in the context of both opposite- and same-sex scenarios using
      community samples from Australia, the United States, and the United Kingdom. The
      study used a quasi-experimental 3 * 2 * 2 * 2 * 3 (prior relationship *
      perpetrator sex * target sex * participant sex * country) independent measures
      design. Participants comprised 2,160 members of the community, each receiving 1
      of 12 versions of a hypothetical scenario and responding to scale items
      concerning the situation described. The findings support previous research, with
      scenarios involving a stranger (rather than an acquaintance or ex-partner), and
      scenarios involving a male perpetrator and a female target, being considered the
      most serious. The findings further indicate that female observers identify more
      closely with the role of the victim and male observers identify more closely with
      the role of the perpetrator, regardless of victim and perpetrator sex, and that
      differences in the findings across the three countries may be affected by
      location to a small but significant degree. 

PMID- 25392388
TI  - A Gender Comparison of Motivations for Physical Dating Violence Among College
      Students.
AB  - There are limited empirical investigations that directly compare men and women's
      motivations, or reasons, for perpetrating physical dating violence (DV). In an
      attempt to further understand whether men and women have similar or different
      motives for physical DV, the purpose of the current study was to conduct a gender
      comparison of motives in a sample of male (n = 163) and female (n = 319) college
      students. Motivations for physical DV were classified according to seven broad
      categories proposed by Langhinrichsen-Rohling and colleagues: (a) power/control,
      (b) self-defense, (c) expression of negative emotion (e.g., anger), (d)
      communication difficulties, (e) retaliation, (f) jealousy, and (g) other (e.g.,
      because it was sexually arousing, the influence of alcohol, the influence of
      drugs). The prevalence of physical violence perpetration in the overall sample
      was 29.4%. Results indicated that communication difficulties and self-defense
      were among the most frequently endorsed motive categories for both male and
      female perpetrated DV. In addition, results demonstrated gender similarity in all
      of the examined motive categories. Research and clinical implications are
      discussed. 

PMID- 25392389
TI  - Depression and Self-Rated Health Among Rural Women Who Experienced Adolescent
      Dating Abuse: A Mixed Methods Study.
AB  - This study used mixed methods to examine the experiences and health of rural,
      young adult women (N = 100) who self-reported past experience of physical,
      emotional and verbal, sexual, and relational abuse in adolescent dating
      relationships. Few studies have examined the lasting health ramifications of
      adolescent dating abuse adolescent dating abuse in rural populations, and almost
      no mixed methods studies have explored adolescent dating abuse. Participants
      completed questionnaires on demographics, relationship behaviors, and mental
      health symptoms. A subsample (n = 10) of participants also completed semi
      structured, in-depth interviews with the primary investigator. Results suggest
      that depressive symptoms and self-rating of health in these women are associated
      with particular kinds and severity of abusive experiences, and that adolescent
      dating abuse has ramifications for health and development beyond the duration of
      the original relationship. Self-rated health (SRH) was inversely associated with
      abusive behaviors in the relationship, whereas depressive symptoms were
      positively correlated with such behaviors. Self-rated health was also negatively
      correlated with depressive symptoms. The results of this study represent an
      important step toward establishing lifetime health risks posed by adolescent
      dating abuse. 

PMID- 25392390
TI  - User Violence and Nursing Staff Burnout: The Modulating Role of Job Satisfaction.
AB  - Exposure to patient violence in health staff can lead to the onset of burnout in
      these workers. The main goal of this investigation is to study how exposure to
      this kind of violence affects onset of burnout and to appraise the role of job
      satisfaction as a modulating variable. A descriptive, cross-sectional study was
      carried out using a self-administered anonymous questionnaire with the nursing
      staff of all the public hospitals of the Region of Murcia (Spain), obtaining a
      sample of 1,489 health professionals. From the results obtained, we underline the
      modulating role of extrinsic job satisfaction in the relationship between
      nonphysical violence and emotional exhaustion, and the protective effect of job
      satisfaction on the impact of nonphysical violence and the level of cynicism. No
      effects of job satisfaction in the relationship between physical violence and
      burnout were observed. We therefore conclude that experiencing nonphysical
      aggression has a lower impact on the psychological health of workers who are
      satisfied with their job, and interventions aimed at increasing these workers'
      extrinsic job satisfaction are highly recommended. 

PMID- 25392391
TI  - Victims' Responses to Stalking: An Examination of Fear Levels and Coping
      Strategies.
AB  - Fear for the stalking victim's own safety or the safety of people close to them
      is of primary research interest due to the fact that fear is often required as a
      necessary condition for repetitive intrusive behavior to be defined as stalking.
      This study examines factors that increase levels of fear in stalking victims and
      analyzes their coping strategies, making use of data from a victimization survey
      among citizens of the Czech Republic (N = 2,503). Overall, 147 stalking victims
      were identified in the sample. Results show that female victims, those stalked by
      male offenders, and victims pursued over a long period of time, are most fearful.
      Higher levels of fear are elicited by strangers as opposed to partners or
      acquaintances. Among stalking practices, only direct aggression is significantly
      associated with fear, whereas monitoring the victim (comprising typical stalking
      behavior such as following the victim) increases the perception of the
      seriousness of stalking, but does not influence the victim's fear. In addition,
      three behavioral coping strategies have been identified: proactive behavior (47%
      of victims), avoidance (30%), and passivity (23%). The examination of the
      association between these coping strategies and victims' fear reveals that female
      victims, whose behavior is proactive, express higher levels of fear than male
      victims and than those choosing avoidance or passivity strategies. Overall, the
      study confirms gender differences in both the level of fear and coping
      strategies, and lends further support to appeals for eliminating the fear
      requirement from the stalking definition. 

PMID- 25392392
TI  - Experiences of Intimate Partner Violence and Subsequent Police Reporting Among
      Lesbian, Gay, Bisexual, Transgender, and Queer Adults in Colorado: Comparing
      Rates of Cisgender and Transgender Victimization.
AB  - Research indicates that lesbian, gay, bisexual, transgender, and queer (LGBTQ)
      individuals are at high risk of victimization by others and that transgender
      individuals may be at even higher risk than their cisgender LGBQ peers. In
      examining partner violence in particular, extant literature suggests that LGBTQ
      individuals are at equal or higher risk of partner violence victimization
      compared with their heterosexual peers. As opposed to sexual orientation, there
      is little research on gender identity and partner violence within the LGBTQ
      literature. In the current study, the authors investigated intimate partner
      violence (IPV) in a large sample of LGBTQ adults (N = 1,139) to determine
      lifetime prevalence and police reporting in both cisgender and transgender
      individuals. Results show that more than one fifth of all participants ever
      experienced partner violence, with transgender participants demonstrating
      significantly higher rates than their cisgender peers. Implications focus on the
      use of inclusive language as well as future research and practice with LGBTQ IPV
      victims. 

PMID- 25392393
TI  - The Prevalence of Potentially Victimizing Events, Poly-Victimization, and Its
      Association to Sociodemographic Factors: A Swedish Youth Survey.
AB  - Studying the extent to which children are exposed to victimizing events is
      important to fully understand the effect of such exposure in shaping them as
      adults. The aim of this study was to use self-report by adolescents to measure
      the prevalence of victimizing events and of poly-victimization. A representative
      sample of 5,960 students (aged 17) from high schools in Sweden was given the self
      administrated version of the Juvenile Victimization Questionnaire (JVQ) along
      with questions concerning gender, birthplace, parents' birthplace and employment,
      residence, educational program, and municipality size. The results show that
      84.1% (83.0% young men and 85.2% young women) of the students had experienced
      victimization during their lifetime, and 10.3% were categorized as poly-victims
      (8.1% young men and 12.5% young women; OR = 1.62, 95% confidence interval [CI] =
      [1.35, 1.94]). Adolescents living with both parents were at lower risk of any
      form of victimization for both genders, while females were at higher risk of
      maltreatment, peer victimization, and, most significantly, sexual victimization.
      In conclusion, the vast majority of young people have been victimized during
      their lifetime. A greater awareness of the impact of these victimizing events on
      children and adolescents is important as a basis for providing a safer milieu and
      establishing better interventions, especially for those that have been victimized
      on multiple occasions. The high-exposure group was determined by using >=10
      events as a cutoff. Findings on this group corresponded with findings in other
      international studies regarding distribution, elevated risk for females, and the
      possibility of limiting the effects of victimization by modifying living
      conditions.

PMID- 25392394
TI  - A Qualitative Study of Intimate Partner Violence Among Women in Nigeria.
AB  - Negative health outcomes caused by intimate partner violence (IPV) have been
      recognized as a public health problem with extensive effects on the society.
      Cultural and traditional beliefs that reinforce IPV in Nigeria need to be
      understood to guide public health approaches aimed at preventing IPV. The purpose
      of this study was to determine women's attitudes and societal norms that support
      IPV, causes and consequences of IPV, and coping strategies, and to document
      suggested measures to prevent it. Six focus group discussions (FGDs) were
      conducted among 56 women aged 15 to 49 years purposively selected from rural and
      urban communities in Akinyele Local Government Area (LGA) of Oyo State, Nigeria.
      The FGDs were conducted in Yoruba language, translated to English, and analyzed
      using thematic approach. Findings were grouped into six major themes: triggers,
      societal norms, attitude, consequences, coping strategies, and preventive
      measures. Women reported experience of physical, psychological, and sexual
      violence and controlling behavior. Major causes of IPV reported by the women were
      having more money than partner, and building a house or having a business without
      partner's knowledge. Most participants reported that social norms dictate that a
      woman should have full regard for in-laws, and submit to and agree with all that
      the partner says and does. Most of the discussants in both the urban and rural
      areas reported that violence in any form is not justifiable or acceptable.
      Participants mentioned various ways through which IPV negatively impacted on
      women's health such as depression, hypertension, and damage to the reproductive
      system. They were however willing to endure suffering because of their children.
      Women who experienced IPV reported to close relatives but did not seek legal
      redress because these were unavailable. Ending IPV requires long-term commitment
      and strategies involving contributions from the government, community, and the
      family. 

PMID- 25392395
TI  - Rapid intra-adrenal feedback regulation of glucocorticoid synthesis.
AB  - The hypothalamic-pituitary-adrenal axis is a vital neuroendocrine system that
      regulates the secretion of glucocorticoid hormones from the adrenal glands. This
      system is characterized by a dynamic ultradian hormonal oscillation, and in
      addition is highly responsive to stressful stimuli. We have recently shown that a
      primary mechanism generating this ultradian rhythm is a systems-level interaction
      where adrenocorticotrophin hormone (ACTH) released from the pituitary stimulates
      the secretion of adrenal glucocorticoids, which in turn feedback at the level of
      the pituitary to rapidly inhibit ACTH secretion. In this study, we combine
      experimental physiology and mathematical modelling to investigate intra-adrenal
      mechanisms regulating glucocorticoid synthesis. Our modelling results suggest
      that glucocorticoids can inhibit their own synthesis through a very rapid (within
      minutes), presumably non-genomic, intra-adrenal pathway. We present further
      evidence for the existence of a short time delay in this intra-adrenal
      inhibition, and also that at the initiation of each ACTH stimulus, this local
      feedback mechanism is rapidly antagonized, presumably via activation of the
      specific ACTH receptor (MC2R) signalling pathway. This mechanism of intra-adrenal
      inhibition enables the gland to rapidly release glucocorticoids while at the same
      time preventing uncontrolled release of glucocorticoids in response to large
      surges in ACTH associated with stress. 

PMID- 25392396
TI  - A jump persistent turning walker to model zebrafish locomotion.
AB  - Zebrafish are gaining momentum as a laboratory animal species for the
      investigation of several functional and dysfunctional biological processes.
      Mathematical models of zebrafish behaviour are expected to considerably aid in
      the design of hypothesis-driven studies by enabling preliminary in silico tests
      that can be used to infer possible experimental outcomes without the use of
      zebrafish. This study is motivated by observations of sudden, drastic changes in
      zebrafish locomotion in the form of large deviations in turn rate. We demonstrate
      that such deviations can be captured through a stochastic mean reverting jump
      diffusion model, a process that is commonly used in financial engineering to
      describe large changes in the price of an asset. The jump process-based model is
      validated on trajectory data of adult subjects swimming in a shallow circular
      tank obtained from an overhead camera. Through statistical comparison of the
      empirical distribution of the turn rate against theoretical predictions, we
      demonstrate the feasibility of describing zebrafish as a jump persistent turning
      walker. The critical role of the jump term is assessed through comparison with a
      simplified mean reversion diffusion model, which does not allow for describing
      the heavy-tailed distributions observed in the fish turn rate. 

PMID- 25392397
TI  - Nanobiocatalyst advancements and bioprocessing applications.
AB  - The nanobiocatalyst (NBC) is an emerging innovation that synergistically
      integrates advanced nanotechnology with biotechnology and promises exciting
      advantages for improving enzyme activity, stability, capability and engineering
      performances in bioprocessing applications. NBCs are fabricated by immobilizing
      enzymes with functional nanomaterials as enzyme carriers or containers. In this
      paper, we review the recent developments of novel nanocarriers/nanocontainers
      with advanced hierarchical porous structures for retaining enzymes, such as
      nanofibres (NFs), mesoporous nanocarriers and nanocages. Strategies for
      immobilizing enzymes onto nanocarriers made from polymers, silicas, carbons and
      metals by physical adsorption, covalent binding, cross-linking or specific ligand
      spacers are discussed. The resulting NBCs are critically evaluated in terms of
      their bioprocessing performances. Excellent performances are demonstrated through
      enhanced NBC catalytic activity and stability due to conformational changes upon
      immobilization and localized nanoenvironments, and NBC reutilization by
      assembling magnetic nanoparticles into NBCs to defray the high operational costs
      associated with enzyme production and nanocarrier synthesis. We also highlight
      several challenges associated with the NBC-driven bioprocess applications,
      including the maturation of large-scale nanocarrier synthesis, design and
      development of bioreactors to accommodate NBCs, and long-term operations of NBCs.
      We suggest these challenges are to be addressed through joint collaboration of
      chemists, engineers and material scientists. Finally, we have demonstrated the
      great potential of NBCs in manufacturing bioprocesses in the near future through
      successful laboratory trials of NBCs in carbohydrate hydrolysis, biofuel
      production and biotransformation. 

PMID- 25392398
TI  - Predicting power-optimal kinematics of avian wings.
AB  - A theoretical model of avian flight is developed which simulates wing motion
      through a class of methods known as predictive simulation. This approach uses
      numerical optimization to predict power-optimal kinematics of avian wings in
      hover, cruise, climb and descent. The wing dynamics capture both aerodynamic and
      inertial loads. The model is used to simulate the flight of the pigeon, Columba
      livia, and the results are compared with previous experimental measurements. In
      cruise, the model unearths a vast range of kinematic modes that are capable of
      generating the required forces for flight. The most efficient mode uses a near
      vertical stroke-plane and a flexed-wing upstroke, similar to kinematics recorded
      experimentally. In hover, the model predicts that the power-optimal mode uses an
      extended-wing upstroke, similar to hummingbirds. In flexing their wings, pigeons
      are predicted to consume 20% more power than if they kept their wings full
      extended, implying that the typical kinematics used by pigeons in hover are
      suboptimal. Predictions of climbing flight suggest that the most energy-efficient
      way to reach a given altitude is to climb as steeply as possible, subjected to
      the availability of power. 

PMID- 25392399
TI  - Inelastic behaviour of collagen networks in cell-matrix interactions and
      mechanosensation.
AB  - The mechanical properties of extracellular matrix proteins strongly influence
      cell-induced tension in the matrix, which in turn influences cell function.
      Despite progress on the impact of elastic behaviour of matrix proteins on cell
      matrix interactions, little is known about the influence of inelastic behaviour,
      especially at the large and slow deformations that characterize cell-induced
      matrix remodelling. We found that collagen matrices exhibit deformation rate
      dependent behaviour, which leads to a transition from pronounced elastic
      behaviour at fast deformations to substantially inelastic behaviour at slow
      deformations (1 MUm min(-1), similar to cell-mediated deformation). With slow
      deformations, the inelastic behaviour of floating gels was sensitive to collagen
      concentration, whereas attached gels exhibited similar inelastic behaviour
      independent of collagen concentration. The presence of an underlying rigid
      support had a similar effect on cell-matrix interactions: cell-induced
      deformation and remodelling were similar on 1 or 3 mg ml(-1) attached collagen
      gels while deformations were two- to fourfold smaller in floating gels of high
      compared with low collagen concentration. In cross-linked collagen matrices,
      which did not exhibit inelastic behaviour, cells did not respond to the presence
      of the underlying rigid foundation. These data indicate that at the slow rates of
      collagen compaction generated by fibroblasts, the inelastic responses of collagen
      gels, which are influenced by collagen concentration and the presence of an
      underlying rigid foundation, are important determinants of cell-matrix
      interactions and mechanosensation. 

PMID- 25392400
TI  - Altered swelling and ion fluxes in articular cartilage as a biomarker in
      osteoarthritis and joint immobilization: a computational analysis.
AB  - In healthy cartilage, mechano-electrochemical phenomena act together to maintain
      tissue homeostasis. Osteoarthritis (OA) and degenerative diseases disrupt this
      biological equilibrium by causing structural deterioration and subsequent
      dysfunction of the tissue. Swelling and ion flux alteration as well as abnormal
      ion distribution are proposed as primary indicators of tissue degradation. In
      this paper, we present an extension of a previous three-dimensional computational
      model of the cartilage behaviour developed by the authors to simulate the
      contribution of the main tissue components in its behaviour. The model considers
      the mechano-electrochemical events as concurrent phenomena in a three-dimensional
      environment. This model has been extended here to include the effect of repulsion
      of negative charges attached to proteoglycans. Moreover, we have studied the
      fluctuation of these charges owning to proteoglycan variations in healthy and
      pathological articular cartilage. In this sense, standard patterns of healthy and
      degraded tissue behaviour can be obtained which could be a helpful diagnostic
      tool. By introducing measured properties of unhealthy cartilage into the
      computational model, the severity of tissue degeneration can be predicted
      avoiding complex tissue extraction and subsequent in vitro analysis. In this
      work, the model has been applied to monitor and analyse cartilage behaviour at
      different stages of OA and in both short (four, six and eight weeks) and long
      term (11 weeks) fully immobilized joints. Simulation results showed marked
      differences in the corresponding swelling phenomena, in outgoing cation fluxes
      and in cation distributions. Furthermore, long-term immobilized patients display
      similar swelling as well as fluxes and distribution of cations to patients in the
      early stages of OA, thus, preventive treatments are highly recommended to avoid
      tissue deterioration. 

PMID- 25392401
TI  - Electrical spiking in bacterial biofilms.
AB  - In nature, biofilms are the most common form of bacterial growth. In biofilms,
      bacteria display coordinated behaviour to perform specific functions. Here, we
      investigated electrical signalling as a possible driver in biofilm sociobiology.
      Using a multi-electrode array system that enables high spatio-temporal
      resolution, we studied the electrical activity in two biofilm-forming strains and
      one non-biofilm-forming strain. The action potential rates monitored during
      biofilm-forming bacterial growth exhibited a one-peak maximum with a long tail,
      corresponding to the highest biofilm development. This peak was not observed for
      the non-biofilm-forming strain, demonstrating that the intensity of the
      electrical activity was not linearly related to the bacterial density, but was
      instead correlated with biofilm formation. Results obtained indicate that the
      analysis of the spatio-temporal electrical activity of bacteria during biofilm
      formation can open a new frontier in the study of the emergence of collective
      microbial behaviour. 

PMID- 25392402
TI  - Evolution on neutral networks accelerates the ticking rate of the molecular
      clock.
AB  - Large sets of genotypes give rise to the same phenotype, because phenotypic
      expression is highly redundant. Accordingly, a population can accept mutations
      without altering its phenotype, as long as the genotype mutates into another one
      on the same set. By linking every pair of genotypes that are mutually accessible
      through mutation, genotypes organize themselves into neutral networks (NNs).
      These networks are known to be heterogeneous and assortative, and these
      properties affect the evolutionary dynamics of the population. By studying the
      dynamics of populations on NNs with arbitrary topology, we analyse the effect of
      assortativity, of NN (phenotype) fitness and of network size. We find that the
      probability that the population leaves the network is smaller the longer the time
      spent on it. This progressive 'phenotypic entrapment' entails a systematic
      increase in the overdispersion of the process with time and an acceleration in
      the fixation rate of neutral mutations. We also quantify the variation of these
      effects with the size of the phenotype and with its fitness relative to that of
      neighbouring alternatives. 

PMID- 25392403
TI  - Non-uniform breaking of molecular bonds, peripheral morphology and releasable
      adhesion by elastic anisotropy in bio-adhesive contacts.
AB  - Biological adhesive contacts are usually of hierarchical structures, such as the
      clustering of hundreds of sub-micrometre spatulae on keratinous hairs of gecko
      feet, or the clustering of molecular bonds into focal contacts in cell adhesion.
      When separating these interfaces, releasable adhesion can be accomplished by
      asymmetric alignment of the lowest scale discrete bonds (such as the inclined
      spatula that leads to different peeling force when loading in different
      directions) or by elastic anisotropy. However, only two-dimensional contact has
      been analysed for the latter method (Chen & Gao 2007 J. Mech. Phys. Solids 55,
      1001-1015 (doi:10.1016/j.jmps.2006.10.008)). Important questions such as the
      three-dimensional contact morphology, the maximum to minimum pull-off force ratio
      and the tunability of releasable adhesion cannot be answered. In this work, we
      developed a three-dimensional cohesive interface model with fictitious viscosity
      that is capable of simulating the de-adhesion instability and the peripheral
      morphology before and after the onset of instability. The two-dimensional
      prediction is found to significantly overestimate the maximum to minimum pull-off
      force ratio. Based on an interface fracture mechanics analysis, we conclude that
      (i) the maximum and minimum pull-off forces correspond to the largest and
      smallest contact stiffness, i.e. 'stiff-adhere and compliant-release', (ii) the
      fracture toughness is sensitive to the crack morphology and the initial contact
      shape can be designed to attain a significantly higher maximum-to-minimum pull
      off force ratio than a circular contact, and (iii) since the adhesion is
      accomplished by clustering of discrete bonds or called bridged crack in terms of
      fracture mechanics terminology, the above conclusions can only be achieved when
      the bridging zone is significantly smaller than the contact size. This adhesion
      fracture analogy study leads to mechanistic predictions that can be readily used
      to design biomimetics and releasable adhesives. 

PMID- 25392404
TI  - Enhanced adhesion of bioinspired nanopatterned elastomers via colloidal surface
      assembly.
AB  - We describe a scalable method to fabricate nanopatterned bioinspired dry
      adhesives using colloidal lithography. Close-packed monolayers of polystyrene
      particles were formed at the air/water interface, on which polydimethylsiloxane
      (PDMS) was applied. The order of the colloidal monolayer and the immersion depth
      of the particles were tuned by altering the pH and ionic strength of the water.
      Initially, PDMS completely wetted the air/water interface outside the monolayer,
      thereby compressing the monolayer as in a Langmuir trough; further application of
      PDMS subsequently covered the colloidal monolayers. PDMS curing and particle
      extraction resulted in elastomers patterned with nanodimples. Adhesion and
      friction of these nanopatterned surfaces with varying dimple depth were studied
      using a spherical probe as a counter-surface. Compared with smooth surfaces,
      adhesion of nanopatterned surfaces was enhanced, which is attributed to an energy
      dissipating mechanism during pull-off. All nanopatterned surfaces showed a
      significant decrease in friction compared with smooth surfaces. 

PMID- 25392405
TI  - Tissue-specific transcriptome sequencing analysis expands the non-human primate
      reference transcriptome resource (NHPRTR).
AB  - The non-human primate reference transcriptome resource (NHPRTR, available online
      at http://nhprtr.org/) aims to generate comprehensive RNA-seq data from a wide
      variety of non-human primates (NHPs), from lemurs to hominids. In the 2012 Phase
      I of the NHPRTR project, 19 billion fragments or 3.8 terabases of transcriptome
      sequences were collected from pools of ~ 20 tissues in 15 species and subspecies.
      Here we describe a major expansion of NHPRTR by adding 10.1 billion fragments of
      tissue-specific RNA-seq data. For this effort, we selected 11 of the original 15
      NHP species and subspecies and constructed total RNA libraries for the same ~ 15
      tissues in each. The sequence quality is such that 88% of the reads align to
      human reference sequences, allowing us to compute the full list of expression
      abundance across all tissues for each species, using the reads mapped to human
      genes. This update also includes improved transcript annotations derived from RNA
      seq data for rhesus and cynomolgus macaques, two of the most commonly used NHP
      models and additional RNA-seq data compiled from related projects. Together,
      these comprehensive reference transcriptomes from multiple primates serve as a
      valuable community resource for genome annotation, gene dynamics and comparative
      functional analysis.

PMID- 25392406
TI  - VirHostNet 2.0: surfing on the web of virus/host molecular interactions data.
AB  - VirHostNet release 2.0 (http://virhostnet.prabi.fr) is a knowledgebase dedicated
      to the network-based exploration of virus-host protein-protein interactions.
      Since the previous VirhostNet release (2009), a second run of manual curation was
      performed to annotate the new torrent of high-throughput protein-protein
      interactions data from the literature. This resource is shared publicly, in PSI
      MI TAB 2.5 format, using a PSICQUIC web service. The new interface of VirHostNet
      2.0 is based on Cytoscape web library and provides a user-friendly access to the
      most complete and accurate resource of virus-virus and virus-host protein-protein
      interactions as well as their projection onto their corresponding host cell
      protein interaction networks. We hope that the VirHostNet 2.0 system will
      facilitate systems biology and gene-centered analysis of infectious diseases and
      will help to identify new molecular targets for antiviral drugs design. This
      resource will also continue to help worldwide scientists to improve our knowledge
      on molecular mechanisms involved in the antiviral response mediated by the cell
      and in the viral strategies selected by viruses to hijack the host immune system.

PMID- 25392407
TI  - SEVA 2.0: an update of the Standard European Vector Architecture for de-/re
      construction of bacterial functionalities.
AB  - The Standard European Vector Architecture 2.0 database (SEVA-DB 2.0,
      http://seva.cnb.csic.es) is an improved and expanded version of the platform
      released in 2013 (doi: 10.1093/nar/gks1119) aimed at assisting the choice of
      optimal genetic tools for de-constructing and re-constructing complex prokaryotic
      phenotypes. By adopting simple compositional rules, the SEVA standard facilitates
      combinations of functional DNA segments that ease both the analysis and the
      engineering of diverse Gram-negative bacteria for fundamental or biotechnological
      purposes. The large number of users of the SEVA-DB during its first two years of
      existence has resulted in a valuable feedback that we have exploited for fixing
      DNA sequence errors, improving the nomenclature of the SEVA plasmids, expanding
      the vector collection, adding new features to the web interface and encouraging
      contributions of materials from the community of users. The SEVA platform is also
      adopting the Synthetic Biology Open Language (SBOL) for electronic-like
      description of the constructs available in the collection and their interfacing
      with genetic devices developed by other Synthetic Biology communities. We
      advocate the SEVA format as one interim asset for the ongoing transition of
      genetic design of microorganisms from being a trial-and-error endeavor to become
      an authentic engineering discipline. 

PMID- 25392408
TI  - The UCSC Cancer Genomics Browser: update 2015.
AB  - The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) is a web-based
      application that integrates relevant data, analysis and visualization, allowing
      users to easily discover and share their research observations. Users can explore
      the relationship between genomic alterations and phenotypes by visualizing
      various -omic data alongside clinical and phenotypic features, such as age,
      subtype classifications and genomic biomarkers. The Cancer Genomics Browser
      currently hosts 575 public datasets from genome-wide analyses of over 227,000
      samples, including datasets from TCGA, CCLE, Connectivity Map and TARGET. Users
      can download and upload clinical data, generate Kaplan-Meier plots dynamically,
      export data directly to Galaxy for analysis, plus generate URL bookmarks of
      specific views of the data to share with others.

PMID- 25392409
TI  - GEM2Net: from gene expression modeling to -omics networks, a new CATdb module to
      investigate Arabidopsis thaliana genes involved in stress response.
AB  - CATdb (http://urgv.evry.inra.fr/CATdb) is a database providing a public access to
      a large collection of transcriptomic data, mainly for Arabidopsis but also for
      other plants. This resource has the rare advantage to contain several thousands
      of microarray experiments obtained with the same technical protocol and analyzed
      by the same statistical pipelines. In this paper, we present GEM2Net, a new
      module of CATdb that takes advantage of this homogeneous dataset to mine co
      expression units and decipher Arabidopsis gene functions. GEM2Net explores 387
      stress conditions organized into 18 biotic and abiotic stress categories. For
      each one, a model-based clustering is applied on expression differences to
      identify clusters of co-expressed genes. To characterize functions associated
      with these clusters, various resources are analyzed and integrated: Gene
      Ontology, subcellular localization of proteins, Hormone Families, Transcription
      Factor Families and a refined stress-related gene list associated to
      publications. Exploiting protein-protein interactions and transcription factors
      targets interactions enables to display gene networks. GEM2Net presents the
      analysis of the 18 stress categories, in which 17,264 genes are involved and
      organized within 681 co-expression clusters. The meta-data analyses were stored
      and organized to compose a dynamic Web resource.

PMID- 25392410
TI  - RaftProt: mammalian lipid raft proteome database.
AB  - RaftProt (http://lipid-raft-database.di.uq.edu.au/) is a database of mammalian
      lipid raft-associated proteins as reported in high-throughput mass spectrometry
      studies. Lipid rafts are specialized membrane microdomains enriched in
      cholesterol and sphingolipids thought to act as dynamic signalling and sorting
      platforms. Given their fundamental roles in cellular regulation, there is a
      plethora of information on the size, composition and regulation of these membrane
      microdomains, including a large number of proteomics studies. To facilitate the
      mining and analysis of published lipid raft proteomics studies, we have developed
      a searchable database RaftProt. In addition to browsing the studies, performing
      basic queries by protein and gene names, searching experiments by cell, tissue
      and organisms; we have implemented several advanced features to facilitate data
      mining. To address the issue of potential bias due to biochemical preparation
      procedures used, we have captured the lipid raft preparation methods and
      implemented advanced search option for methodology and sample treatment
      conditions, such as cholesterol depletion. Furthermore, we have identified a list
      of high confidence proteins, and enabled searching only from this list of likely
      bona fide lipid raft proteins. Given the apparent biological importance of lipid
      raft and their associated proteins, this database would constitute a key resource
      for the scientific community. 

PMID- 25392411
TI  - PyIgClassify: a database of antibody CDR structural classifications.
AB  - Classification of the structures of the complementarity determining regions
      (CDRs) of antibodies is critically important for antibody structure prediction
      and computational design. We have previously performed a clustering of antibody
      CDR conformations and defined a systematic nomenclature consisting of the CDR,
      length and an integer starting from the largest to the smallest cluster in the
      data set (e.g. L1-11-1). We present PyIgClassify (for Python-based immunoglobulin
      classification; available at http://dunbrack2.fccc.edu/pyigclassify/), a database
      and web server that provides access to assignments of all CDR structures in the
      PDB to our classification system. The database includes assignments to the IMGT
      germline V regions for heavy and light chains for several species. For humanized
      antibodies, the assignment of the frameworks is to human germlines and the CDRs
      to the germlines of mice or other species sources. The database can be searched
      by PDB entry, cluster identifier and IMGT germline group (e.g. human IGHV1). The
      entire database is downloadable so that users may filter the data as needed for
      antibody structure analysis, prediction and design. 

PMID- 25392412
TI  - The Addgene repository: an international nonprofit plasmid and data resource.
AB  - The Addgene Repository (http://www.addgene.org) was founded to accelerate
      research and discovery by improving access to useful, high-quality research
      materials and information. The repository archives plasmids generated by
      scientists, conducts quality control, annotates the associated data and makes the
      plasmids and their data available to the scientific community. Plasmid associated
      data undergoes ongoing curation by members of the scientific community and by
      Addgene scientists. The growing database contains information on >31,000 unique
      plasmids spanning most experimental biological systems and organisms. The library
      includes a large number of plasmid tools for use in a wide variety of research
      areas, such as empty backbones, lentiviral resources, fluorescent protein vectors
      and genome engineering tools. The Addgene Repository database is always evolving
      with new plasmid deposits so it contains currently pertinent resources while
      ensuring the information on earlier deposits is still available. Custom search
      and browse features are available to access information on the diverse
      collection. Extensive educational materials and information are provided by the
      database curators to support the scientists that are accessing the repository's
      materials and data.

PMID- 25392413
TI  - The coffee genome hub: a resource for coffee genomes.
AB  - The whole genome sequence of Coffea canephora, the perennial diploid species
      known as Robusta, has been recently released. In the context of the C. canephora
      genome sequencing project and to support post-genomics efforts, we developed the
      Coffee Genome Hub (http://coffee-genome.org/), an integrative genome information
      system that allows centralized access to genomics and genetics data and analysis
      tools to facilitate translational and applied research in coffee. We provide the
      complete genome sequence of C. canephora along with gene structure, gene product
      information, metabolism, gene families, transcriptomics, syntenic blocks, genetic
      markers and genetic maps. The hub relies on generic software (e.g. GMOD tools)
      for easy querying, visualizing and downloading research data. It includes a
      Genome Browser enhanced by a Community Annotation System, enabling the
      improvement of automatic gene annotation through an annotation editor. In
      addition, the hub aims at developing interoperability among other existing South
      Green tools managing coffee data (phylogenomics resources, SNPs) and/or
      supporting data analyses with the Galaxy workflow manager. 

PMID- 25392415
TI  - Cancer3D: understanding cancer mutations through protein structures.
AB  - The new era of cancer genomics is providing us with extensive knowledge of
      mutations and other alterations in cancer. The Cancer3D database at
      http://www.cancer3d.org gives an open and user-friendly way to analyze cancer
      missense mutations in the context of structures of proteins in which they are
      found. The database also helps users analyze the distribution patterns of the
      mutations as well as their relationship to changes in drug activity through two
      algorithms: e-Driver and e-Drug. These algorithms use knowledge of modular
      structure of genes and proteins to separately study each region. This approach
      allows users to find novel candidate driver regions or drug biomarkers that
      cannot be found when similar analyses are done on the whole-gene level. The
      Cancer3D database provides access to the results of such analyses based on data
      from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE).
      In addition, it displays mutations from over 14,700 proteins mapped to more than
      24,300 structures from PDB. This helps users visualize the distribution of
      mutations and identify novel three-dimensional patterns in their distribution.

PMID- 25392414
TI  - Mechismo: predicting the mechanistic impact of mutations and modifications on
      molecular interactions.
AB  - Systematic interrogation of mutation or protein modification data is important to
      identify sites with functional consequences and to deduce global consequences
      from large data sets. Mechismo (mechismo.russellab.org) enables simultaneous
      consideration of thousands of 3D structures and biomolecular interactions to
      predict rapidly mechanistic consequences for mutations and modifications. As
      useful functional information often only comes from homologous proteins, we
      benchmarked the accuracy of predictions as a function of protein/structure
      sequence similarity, which permits the use of relatively weak sequence
      similarities with an appropriate confidence measure. For protein-protein, protein
      nucleic acid and a subset of protein-chemical interactions, we also developed and
      benchmarked a measure of whether modifications are likely to enhance or diminish
      the interactions, which can assist the detection of modifications with specific
      effects. Analysis of high-throughput sequencing data shows that the approach can
      identify interesting differences between cancers, and application to proteomics
      data finds potential mechanistic insights for how post-translational
      modifications can alter biomolecular interactions. 

PMID- 25392416
TI  - PubAngioGen: a database and knowledge for angiogenesis and related diseases.
AB  - Angiogenesis is the process of generating new blood vessels based on existing
      ones, which is involved in many diseases including cancers, cardiovascular
      diseases and diabetes mellitus. Recently, great efforts have been made to explore
      the mechanisms of angiogenesis in various diseases and many angiogenic factors
      have been discovered as therapeutic targets in anti- or pro-angiogenic drug
      development. However, the resulted information is sparsely distributed and no
      systematical summarization has been made. In order to integrate these related
      results and facilitate the researches for the community, we conducted manual text
      mining from published literature and built a database named as PubAngioGen
      (http://www.megabionet.org/aspd/). Our online application displays a
      comprehensive network for exploring the connection between angiogenesis and
      diseases at multilevels including protein-protein interaction, drug-target,
      disease-gene and signaling pathways among various cells and animal models
      recorded through text-mining. To enlarge the scope of the PubAngioGen
      application, our database also links to other common resources including STRING,
      DrugBank and OMIM databases, which will facilitate understanding the underlying
      molecular mechanisms of angiogenesis and drug development in clinical therapy. 

PMID- 25392417
TI  - CeCaFDB: a curated database for the documentation, visualization and comparative
      analysis of central carbon metabolic flux distributions explored by 13C
      fluxomics.
AB  - The Central Carbon Metabolic Flux Database (CeCaFDB, available at
      http://www.cecafdb.org) is a manually curated, multipurpose and open-access
      database for the documentation, visualization and comparative analysis of the
      quantitative flux results of central carbon metabolism among microbes and animal
      cells. It encompasses records for more than 500 flux distributions among 36
      organisms and includes information regarding the genotype, culture medium, growth
      conditions and other specific information gathered from hundreds of journal
      articles. In addition to its comprehensive literature-derived data, the CeCaFDB
      supports a common text search function among the data and interactive
      visualization of the curated flux distributions with compartmentation information
      based on the Cytoscape Web API, which facilitates data interpretation. The
      CeCaFDB offers four modules to calculate a similarity score or to perform an
      alignment between the flux distributions. One of the modules was built using an
      inter programming algorithm for flux distribution alignment that was specifically
      designed for this study. Based on these modules, the CeCaFDB also supports an
      extensive flux distribution comparison function among the curated data. The
      CeCaFDB is strenuously designed to address the broad demands of biochemists,
      metabolic engineers, systems biologists and members of the -omics community. 

PMID- 25392418
TI  - ValidatorDB: database of up-to-date validation results for ligands and non
      standard residues from the Protein Data Bank.
AB  - Following the discovery of serious errors in the structure of biomacromolecules,
      structure validation has become a key topic of research, especially for ligands
      and non-standard residues. ValidatorDB (freely available at
      http://ncbr.muni.cz/ValidatorDB) offers a new step in this direction, in the form
      of a database of validation results for all ligands and non-standard residues
      from the Protein Data Bank (all molecules with seven or more heavy atoms). Model
      molecules from the wwPDB Chemical Component Dictionary are used as reference
      during validation. ValidatorDB covers the main aspects of validation of
      annotation, and additionally introduces several useful validation analyses. The
      most significant is the classification of chirality errors, allowing the user to
      distinguish between serious issues and minor inconsistencies. Other such analyses
      are able to report, for example, completely erroneous ligands, alternate
      conformations or complete identity with the model molecules. All results are
      systematically classified into categories, and statistical evaluations are
      performed. In addition to detailed validation reports for each molecule,
      ValidatorDB provides summaries of the validation results for the entire PDB, for
      sets of molecules sharing the same annotation (three-letter code) or the same PDB
      entry, and for user-defined selections of annotations or PDB entries. 

PMID- 25392419
TI  - AHTPDB: a comprehensive platform for analysis and presentation of
      antihypertensive peptides.
AB  - AHTPDB (http://crdd.osdd.net/raghava/ahtpdb/) is a manually curated database of
      experimentally validated antihypertensive peptides. Information pertaining to
      peptides with antihypertensive activity was collected from research articles and
      from various peptide repositories. These peptides were derived from 35 major
      sources that include milk, egg, fish, pork, chicken, soybean, etc. In AHTPDB,
      most of the peptides belong to a family of angiotensin-I converting enzyme
      inhibiting peptides. The current release of AHTPDB contains 5978 peptide entries
      among which 1694 are unique peptides. Each entry provides detailed information
      about a peptide like sequence, inhibitory concentration (IC50),
      toxicity/bitterness value, source, length, molecular mass and information related
      to purification of peptides. In addition, the database provides structural
      information of these peptides that includes predicted tertiary and secondary
      structures. A user-friendly web interface with various tools has been developed
      to retrieve and analyse the data. It is anticipated that AHTPDB will be a useful
      and unique resource for the researchers working in the field of antihypertensive
      peptides. 

PMID- 25392420
TI  - COXPRESdb in 2015: coexpression database for animal species by DNA-microarray and
      RNAseq-based expression data with multiple quality assessment systems.
AB  - The COXPRESdb (http://coxpresdb.jp) provides gene coexpression relationships for
      animal species. Here, we report the updates of the database, mainly focusing on
      the following two points. For the first point, we added RNAseq-based gene
      coexpression data for three species (human, mouse and fly), and largely increased
      the number of microarray experiments to nine species. The increase of the number
      of expression data with multiple platforms could enhance the reliability of
      coexpression data. For the second point, we refined the data assessment
      procedures, for each coexpressed gene list and for the total performance of a
      platform. The assessment of coexpressed gene list now uses more reasonable P
      values derived from platform-specific null distribution. These developments
      greatly reduced pseudo-predictions for directly associated genes, thus expanding
      the reliability of coexpression data to design new experiments and to discuss
      experimental results. 

PMID- 25392421
TI  - MiCroKiTS 4.0: a database of midbody, centrosome, kinetochore, telomere and
      spindle.
AB  - We reported an updated database of MiCroKiTS 4.0 (http://microkit.biocuckoo.org)
      for proteins temporally and spatially localized in distinct subcellular positions
      including midbody, centrosome, kinetochore, telomere and mitotic spindle during
      cell division/mitosis. The database was updated from our previously developed
      database of MiCroKit 3.0, which contained 1489 proteins mostly forming super
      complexes at midbody, centrosome and kinetochore from seven eukaryotes. Since the
      telomere and spindle apparatus are critical for cell division, the proteins
      localized at the two positions were also integrated. From the scientific
      literature, we curated 1872 experimentally identified proteins which at least
      locate in one of the five positions from eight species. Then the ortholog
      detection was performed to identify potential MiCroKiTS proteins from 144
      eukaryotic organisms, which contains 66, 45 and 33 species of animals, fungi and
      plants, respectively. In total, 87,983 unique proteins with corresponding
      localization information were integrated into the database. The primary
      references of experimentally identified localizations were provided and the
      fluorescence microscope figures for the localizations of human proteins were
      shown. The orthologous relations between predicted and experimental localizations
      were also present. Taken together, we anticipate the database can serve as a
      useful resource for further analyzing the molecular mechanisms during cell
      division.

PMID- 25392422
TI  - tRFdb: a database for transfer RNA fragments.
AB  - We have created tRFdb, the first database of transfer RNA fragments (tRFs),
      available at http://genome.bioch.virginia.edu/trfdb/. With over 100 small RNA
      libraries analyzed, the database currently contains the sequences and read counts
      of the three classes of tRFs for eight species: R. sphaeroides, S. pombe, D.
      melanogaster, C. elegans, Xenopus, zebra fish, mouse and human, for a total of
      12,877 tRFs. The database can be searched by tRF ID or tRF sequence, and the
      results can be limited by organism. The search results show the genome
      coordinates and names of the tRNAs the sequence may derive from, and there are
      links for the sequence of the tRF and parental tRNA, and links for the read
      counts in all the corresponding small RNA libraries. As a case study for how this
      database may be used, we have shown that a certain class of tRFs, tRF-1s, is
      highly upregulated in B-cell malignancies.

PMID- 25392423
TI  - Profiling small RNA reveals multimodal substructural signals in a Boltzmann
      ensemble.
AB  - As the biomedical impact of small RNAs grows, so does the need to understand
      competing structural alternatives for regions of functional interest. Suboptimal
      structure analysis provides significantly more RNA base pairing information than
      a single minimum free energy prediction. Yet computational enhancements like
      Boltzmann sampling have not been fully adopted by experimentalists since
      identifying meaningful patterns in this data can be challenging. Profiling is a
      novel approach to mining RNA suboptimal structure data which makes the power of
      ensemble-based analysis accessible in a stable and reliable way. Balancing
      abstraction and specificity, profiling identifies significant combinations of
      base pairs which dominate low-energy RNA secondary structures. By design,
      critical similarities and differences are highlighted, yielding crucial
      information for molecular biologists. The code is freely available via
      http://gtfold.sourceforge.net/profiling.html. 

PMID- 25392424
TI  - Expediting topology data gathering for the TOPDB database.
AB  - The Topology Data Bank of Transmembrane Proteins (TOPDB,
      http://topdb.enzim.ttk.mta.hu) contains experimentally determined topology data
      of transmembrane proteins. Recently, we have updated TOPDB from several sources
      and utilized a newly developed topology prediction algorithm to determine the
      most reliable topology using the results of experiments as constraints. In
      addition to collecting the experimentally determined topology data published in
      the last couple of years, we gathered topographies defined by the TMDET algorithm
      using 3D structures from the PDBTM. Results of global topology analysis of
      various organisms as well as topology data generated by high throughput
      techniques, like the sequential positions of N- or O-glycosylations were
      incorporated into the TOPDB database. Moreover, a new algorithm was developed to
      integrate scattered topology data from various publicly available databases and a
      new method was introduced to measure the reliability of predicted topologies. We
      show that reliability values highly correlate with the per protein topology
      accuracy of the utilized prediction method. Altogether, more than 52,000 new
      topology data and more than 2600 new transmembrane proteins have been collected
      since the last public release of the TOPDB database.

PMID- 25392425
TI  - Rfam 12.0: updates to the RNA families database.
AB  - The Rfam database (available at http://rfam.xfam.org) is a collection of non
      coding RNA families represented by manually curated sequence alignments,
      consensus secondary structures and annotation gathered from corresponding
      Wikipedia, taxonomy and ontology resources. In this article, we detail updates
      and improvements to the Rfam data and website for the Rfam 12.0 release. We
      describe the upgrade of our search pipeline to use Infernal 1.1 and demonstrate
      its improved homology detection ability by comparison with the previous version.
      The new pipeline is easier for users to apply to their own data sets, and we
      illustrate its ability to annotate RNAs in genomic and metagenomic data sets of
      various sizes. Rfam has been expanded to include 260 new families, including the
      well-studied large subunit ribosomal RNA family, and for the first time includes
      information on short sequence- and structure-based RNA motifs present within
      families. 

PMID- 25392427
TI  - The life and work of the Dumfries surgeon James Hill (1703-1776): his
      contributions to the management of cancer and of head injury.
AB  - James Hill was apprenticed to the formidable Edinburgh surgeon, physician and
      philosopher George Young from whom he learned the value of careful observation
      and scepticism in medicine. As a surgeon in Dumfries he was able to take
      advantage of newly established medical journals to publish case reports. His book
      Cases in Surgery summarised three aspects of his life's work as a surgeon. In it
      he provides a classical description of the features and transmission of sibbens
      (endemic syphilis) and suggests from careful clinical observation that sibbens
      and venereal syphilis were the same disease. His success with treatment of cancer
      led him to advocate curative rather than palliative excision, a view that ran
      counter to accepted contemporary practice. Hill's ability to diagnose cerebral
      compression caused by bleeding following head injury enabled him to treat this
      successfully by directed trephine and drainage. His results on the treatment of
      head injury were the best to be published in their day and an important addition
      to the increasing understanding of the basis of the management of head injury.

PMID- 25392426
TI  - Helminth.net: expansions to Nematode.net and an introduction to Trematode.net.
AB  - Helminth.net (http://www.helminth.net) is the new moniker for a collection of
      databases: Nematode.net and Trematode.net. Within this collection we provide
      services and resources for parasitic roundworms (nematodes) and flatworms
      (trematodes), collectively known as helminths. For over a decade we have provided
      resources for studying nematodes via our veteran site Nematode.net
      (http://nematode.net). In this article, (i) we provide an update on the
      expansions of Nematode.net that hosts omics data from 84 species and provides
      advanced search tools to the broad scientific community so that data can be mined
      in a useful and user-friendly manner and (ii) we introduce Trematode.net, a site
      dedicated to the dissemination of data from flukes, flatworm parasites of the
      class Trematoda, phylum Platyhelminthes. Trematode.net is an independent
      component of Helminth.net and currently hosts data from 16 species, with
      information ranging from genomic, functional genomic data, enzymatic pathway
      utilization to microbiome changes associated with helminth infections. The
      databases' interface, with a sophisticated query engine as a backbone, is
      intended to allow users to search for multi-factorial combinations of species'
      omics properties. This report describes updates to Nematode.net since its last
      description in NAR, 2012, and also introduces and presents its new sibling site,
      Trematode.net. 

PMID- 25392428
TI  - Two cheers for case reports.

PMID- 25392430
TI  - Calls for restricting the marketing of unhealthy foods to children ignored by
      policy makers: what can we do?

PMID- 25392431
TI  - Widespread misconceptions about obesity.

PMID- 25392434
TI  - Fracture healing and NSAIDs.

PMID- 25392435
TI  - Guidelines for mild head injuries in children.

PMID- 25392436
TI  - Not antagonist treatment.

PMID- 25392437
TI  - Response.

PMID- 25392438
TI  - Approach to the new oral anticoagulants in family practice: part 1: comparing the
      options.
AB  - OBJECTIVE: To compare key features of the new oral anticoagulants (NOACs)
      dabigatran, rivaroxaban, and apixaban-and to address questions that arise when
      comparing the NOACs. SOURCES OF INFORMATION: PubMed was searched for recent
      (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for
      stroke prevention in atrial fibrillation (AF) and for the treatment of acute
      venous thromboembolism (VTE). MAIN MESSAGE: All NOACs are at least as effective
      as warfarin for stroke prevention in patients with nonvalvular AF, and are at
      least as safe in terms of bleeding risk according to 3 large trials. Meta
      analyses of these trials have shown that, compared with warfarin therapy, NOACs
      reduced total mortality, cardiovascular mortality, and intracranial bleeding, and
      there was a trend toward less overall bleeding. Practical advantages of NOACs
      over warfarin include fixed once- or twice-daily oral dosing without the need for
      coagulation monitoring, and few known or defined drug or food interactions.
      Potential drawbacks of NOACs include a risk of bleeding that might be increased
      in patients older than 75 years, increased major gastrointestinal bleeding with
      high-dose dabigatran, increased dyspepsia with dabigatran, the lack of a routine
      laboratory test to reliably measure anticoagulant effect, and the lack of an
      antidote for reversal. No direct comparisons of NOACs have been made in
      randomized controlled trials, and the choice of NOAC is influenced by individual
      patient characteristics, including risk of stroke or VTE, risk of bleeding, and
      comorbidity (eg, renal dysfunction). CONCLUSION: The NOACs represent important
      alternatives in the management of patients with AF and VTE, especially for
      patients who have difficulty accessing regular coagulation monitoring. The
      companion to this article addresses common "what if" questions that arise in the
      long-term clinical follow-up and management of patients receiving NOACs.

PMID- 25392440
TI  - Sugar substitutes during pregnancy.
AB  - QUESTION: I have a pregnant patient who regularly consumes sugar substitutes and
      she asked me if continuing their use would affect her pregnancy or child. What
      should I tell her, and are there certain options that are better for use during
      pregnancy? ANSWER: Although more research is required to fully determine the
      effects of in utero exposure to sugar substitutes, the available data do not
      suggest adverse effects in pregnancy. However, it is recommended that sugar
      substitutes be consumed in moderate amounts, adhering to the acceptable daily
      intake standards set by regulatory agencies.

PMID- 25392439
TI  - Approach to the new oral anticoagulants in family practice: part 2: addressing
      frequently asked questions.
AB  - OBJECTIVE: To address common "what if" questions that arise relating to the long
      term clinical follow-up and management of patients receiving the new oral
      anticoagulants (NOACs). SOURCES OF INFORMATION: For this narrative review, we
      searched the PubMed database for recent (January 2008 to week 32 of 2013)
      clinical studies relating to NOAC use for stroke prevention in atrial
      fibrillation and for the treatment of acute venous thromboembolism. We used this
      evidence base to address prespecified questions relating to NOAC use in primary
      care settings. MAIN MESSAGE: Dabigatran and rivaroxaban should be taken with
      meals to decrease dyspepsia and increase absorption, respectively. There are no
      dietary restrictions with any of the NOACs, beyond moderating alcohol intake, and
      rivaroxaban and apixaban can be crushed if required. The use of acid suppressive
      therapies does not appear to affect the efficacy of the NOACs. As with warfarin,
      patients taking NOACs should avoid long-term use of nonsteroidal anti
      inflammatory and antiplatelet drugs. For patients requiring surgery, generally
      NOACs should be stopped 2 to 5 days before the procedure, depending on bleeding
      risk, and the NOAC should usually be resumed at least 24 hours after surgery.
      Preoperative coagulation testing is generally unnecessary. In patients who
      develop bleeding, minor bleeding typically does not require laboratory testing or
      discontinuation of NOACs; with major bleeding, the focus should be on local
      measures to control the bleeding and supportive care, and coagulation testing
      should be performed. There are currently no antidotes to reverse NOACs. The NOACs
      should not be used in patients with valvular heart disease, prosthetic heart
      valves, cancer-associated deep vein thrombosis, or superficial thrombophlebitis.
      CONCLUSION: Management of "what if" scenarios for patients taking NOACs have been
      proposed, but additional study is needed to address these issues, especially
      periprocedural management and bleeding.

PMID- 25392441
TI  - Giant inverted T waves and substantial QT interval prolongation induced by
      azithromycin in an elderly woman with renal insufficiency.

PMID- 25392442
TI  - Family history of cardiovascular disease.

PMID- 25392443
TI  - Guyana housecall.

PMID- 25392444
TI  - Emilie Gagnon MD CM.

PMID- 25392445
TI  - Our college mosaic.

PMID- 25392448
TI  - Getting deliberate about access.

PMID- 25392449
TI  - Cirque du Monde as a health intervention: perceptions of medical students and
      social circus experts.
AB  - OBJECTIVE: To present Cirque du Soleil's social circus program, Cirque du Monde,
      to explore its potential as a primary health care tool for family physicians.
      DATA SOURCES: A review of the literature in PubMed, the Cochrane Library,
      PsycINFO, LaPresse, Eureka, Google Scholar, and Erudit using the key words
      circus, social circus, Cirque du Monde, and Cirque du Soleil; a Montreal-based
      initiative, Espace Transition, modeled on Cirque du Monde; and personal
      communication with Cirque du Soleil's Social Circus Training Advisor. STUDY
      SELECTION: The first 50 articles or websites identified for each key word in each
      of the databases were examined on the basis of their titles and abstracts in the
      case of articles, and on the basis of their titles and page content in the case
      of websites. Articles and websites that explored an aspect of social circuses or
      that described an intervention that involved circuses were then retained for
      analysis. Because all literature on social circuses was searched, no criterion
      for year of publication was used. SYNTHESIS: No articles on the social circus as
      a health intervention were found. One study on the use of the circus as an
      intervention in schools was identified. It demonstrated an increase in self
      esteem in the children who took part. One study on the use of the circus in a
      First Nations community was found; it contained nonspecific, qualitative
      findings. The other articles identified were merely descriptions of social
      circuses. One website was identified on the use of the social circus to help
      youth who had been treated in a hospital setting for major psychiatric disorders
      to re-enter the community. The team in the pediatric psychiatry department at
      Centre Hospitalier Universitaire Sainte-Justine, the children's hospital in
      Montreal, Que, was contacted; they were leading this project, called Espace
      Transition. The unpublished preliminary findings of its pilot project demonstrate
      substantial improvements in overall patient functioning. According to Cirque du
      Soleil, there are several projects under way around the world researching the
      therapeutic value of social circuses. CONCLUSION: Cirque du Monde is able to
      reach a marginalized population that is otherwise difficult for the health system
      to reach. This program has therapeutic potential because of its target
      population, its promotion of healthy habits, and the support that it offers
      through the group and its workers. Cirque du Soleil is investing heavily in this
      project. The lack of literature yielding robust data on the social circus is
      therefore an important issue.

PMID- 25392450
TI  - Wnt signalling induces accumulation of phosphorylated beta-catenin in two
      distinct cytosolic complexes.
AB  - Wnt/beta-catenin signalling controls development and adult tissue homeostasis and
      causes cancer when inappropriately activated. In unstimulated cells, an Axin1
      centred multi-protein complex phosphorylates the transcriptional co-activator
      beta-catenin, marking it for degradation. Wnt signalling antagonizes beta-catenin
      proteolysis, leading to its accumulation and target gene expression. How Wnt
      stimulation alters the size distribution, composition and activity of endogenous
      Axin1 complexes remains poorly understood. Here, we employed two-dimensional blue
      native/SDS-PAGE to analyse endogenous Axin1 and beta-catenin complexes during Wnt
      signalling. We show that the size range of Axin1 complexes is conserved between
      species and remains largely unaffected by Wnt stimulation. We detect a striking
      Wnt-dependent, cytosolic accumulation of both non-phosphorylated and
      phosphorylated beta-catenin within a 450 kDa Axin1-based complex and in a
      distinct, Axin1-free complex of 200 kDa. These results argue that during Wnt
      stimulation, phosphorylated beta-catenin is released from the Axin1 complex but
      fails to undergo immediate degradation. Importantly, in APC-mutant cancer cells,
      the distribution of Axin1 and beta-catenin complexes strongly resembles that of
      Wnt-stimulated cells. Our findings argue that Wnt signals and APC mutations
      interfere with the turnover of phosphorylated beta-catenin. Furthermore, our
      results suggest that the accumulation of small-sized beta-catenin complexes may
      serve as an indicator of Wnt pathway activity in primary cancer cells. 

PMID- 25392451
TI  - Targeting the INCENP IN-box-Aurora B interaction to inhibit CPC activity in vivo.
AB  - The chromosome passenger complex (CPC) is an essential regulator of mitosis and
      cytokinesis. The CPC consists of Aurora B kinase, inner centromere protein
      (INCENP), and the targeting subunits survivin and borealin/Dasra B. INCENP is a
      scaffolding subunit for the CPC and activates Aurora B via its conserved IN-box
      domain. We show that overexpression of soluble IN-box in HeLa cells affects
      endogenous CPC localization and produces a significant increase in multinucleated
      and micronucleated cells consistent with CPC loss of function. The dominant
      negative effect of soluble IN-box expression depends on residues corresponding to
      hINCENP W845 and/or F881, suggesting that these are essential for Aurora B
      binding in vivo. We then screened a targeted library of small (five to nine
      residues long) circular peptide (CP) IN-box fragments generated using split
      intein circular ligation of proteins and peptides (SICLOPPS) methodology. We
      identified a number of CPs that caused modest but reproducible increases in rates
      of multinucleated and micronucleated cells. Our results provide proof of concept
      that inhibition of the Aurora B-IN-box interaction is a viable strategy for
      interfering with CPC function in vivo. 

PMID- 25392453
TI  - Cannabinoid-related olfactory neuroscience in mice and humans.

PMID- 25392454
TI  - Editor's Note: obesity rates.

PMID- 25392452
TI  - A novel Bcr-Abl-mTOR-eIF4A axis regulates IRES-mediated translation of LEF-1.
AB  - Internal ribosome entry sites (IRESs) in cellular mRNAs direct expression of
      growth-promoting factors through an alternative translation mechanism that has
      yet to be fully defined. Lymphoid enhancer factor-1 (LEF-1), a Wnt-mediating
      transcription factor important for cell survival and metastasis in cancer, is
      produced via IRES-directed translation, and its mRNA is frequently upregulated in
      malignancies, including chronic myeloid leukaemia (CML). In this study, we
      determined that LEF1 expression is regulated by Bcr-Abl, the oncogenic protein
      that drives haematopoietic cell transformation to CML. We have previously shown
      that the LEF1 5' untranslated region recruits a complex of proteins to its IRES,
      including the translation initiation factor eIF4A. In this report, we use two
      small molecule inhibitors, PP242 (dual mTOR (mammalian target of rapamycin)
      kinase inhibitor) and hippuristanol (eIF4A inhibitor), to define IRES regulation
      via a Bcr-Abl-mTOR-eIF4A axis in CML cell lines and primary patient leukaemias.
      We found that LEF1 and other IRESs are uniquely sensitive to the activities of
      Bcr-Abl/mTOR. Most notably, we discovered that eIF4A, an RNA helicase, elicits
      potent non-canonical effects on the LEF1 IRES. Hippuristanol inhibition of eIF4A
      stalls translation of IRES mRNA and triggers dissociation from polyribosomes. We
      propose that a combination drug strategy which targets mTOR and IRES-driven
      translation disrupts key factors that contribute to growth and proliferation in
      CML. 

PMID- 25392455
TI  - Update to A.S.P.E.N. position paper: clinical role for alternative intravenous
      fat emulsions.

PMID- 25392457
TI  - Should foam made with physiologic gases be the standard in sclerotherapy?
AB  - OBJECTIVES: The aim of this paper is to look at the pros and cons of using
      physiologic gas to produce foam for use in sclerotherapy. With the expanding use
      of foam sclerotherapy, there have been increased reports of transient neurologic
      adverse events such as visual disturbance. Although rare, increased numbers of
      serious adverse events such as transient ischemic attacks (TIAs) and stroke have
      been described. These events are seen more often in patients who have migraine
      with aura and those with a right-to-left shunt. METHODS: A literature search of
      the databases Ovid and Google Scholar was performed for studies looking
      specifically at neurologic side effects associated with sclerotherapy and use of
      physiologic foams. Included studies were randomized controlled trials, meta
      analyses, review articles, observational studies and case studies. RESULTS:
      Although physiologic gases have been shown in several studies to reduce the
      incidence of visual disturbance, increasing evidence from recent studies suggest
      endothelin, rather than gas bubbles to be the cause of these side effects. The
      cause of stroke and TIA has not been proven and occlusion of cerebral arterioles
      from gas emboli should still be considered. Many authors state that only good
      quality foam be injected and volumes should be kept low in an attempt to prevent
      these rare, but potentially serious events. Foam made with physiologic gases are
      more biocompatible compared to air-based foam and have been found to be at least
      as effective in sclerotherapy as foam made with room air. CONCLUSION: The use of
      physiologic gases should be considered for those at increased risk of neurologic
      side effects such as migraineurs with aura and those with a known PFO.
      Additionally, as there are few disadvantages to the use of physiologic foam, the
      use of CO2 or CO2/O2 foam should be considered in all patients receiving foam
      sclerotherapy.

PMID- 25392458
TI  - Temperature and acidification variability reduce physiological performance in the
      intertidal zone porcelain crab Petrolisthes cinctipes.
AB  - We show here that increased variability of temperature and pH synergistically
      negatively affects the energetics of intertidal zone crabs. Under future climate
      scenarios, coastal ecosystems are projected to have increased extremes of low
      tide-associated thermal stress and ocean acidification-associated low pH, the
      individual or interactive effects of which have yet to be determined. To
      characterize energetic consequences of exposure to increased variability of pH
      and temperature, we exposed porcelain crabs, Petrolisthes cinctipes, to
      conditions that simulated current and future intertidal zone thermal and pH
      environments. During the daily low tide, specimens were exposed to no, moderate
      or extreme heating, and during the daily high tide experienced no, moderate or
      extreme acidification. Respiration rate and cardiac thermal limits were assessed
      following 2.5 weeks of acclimation. Thermal variation had a larger overall effect
      than pH variation, though there was an interactive effect between the two
      environmental drivers. Under the most extreme temperature and pH combination,
      respiration rate decreased while heat tolerance increased, indicating a smaller
      overall aerobic energy budget (i.e. a reduced O2 consumption rate) of which a
      larger portion is devoted to basal maintenance (i.e. greater thermal tolerance
      indicating induction of the cellular stress response). These results suggest the
      potential for negative long-term ecological consequences for intertidal
      ectotherms exposed to increased extremes in pH and temperature due to reduced
      energy for behavior and reproduction. 

PMID- 25392459
TI  - Mechanisms of naturally evolved ethanol resistance in Drosophila melanogaster.
AB  - The decaying fruit in which Drosophila melanogaster feed and breed can contain
      ethanol in concentrations as high as 6-7%. In this cosmopolitan species,
      populations from temperate regions are consistently more resistant to ethanol
      poisoning than populations from the tropics, but little is known about the
      physiological basis of this difference. I show that when exposed to low levels of
      ethanol vapor, flies from a tropical African population accumulated 2-3 times
      more internal ethanol than flies from a European population, giving evidence that
      faster ethanol catabolism by European flies contributes to the resistance
      difference. Using lines differing only in the origin of their third chromosome,
      however, I show that faster ethanol elimination cannot fully explain the
      resistance difference, because relative to African third chromosomes, European
      third chromosomes confer substantially higher ethanol resistance, while having
      little effect on internal ethanol concentrations. European third chromosomes also
      confer higher resistance to acetic acid, a metabolic product of ethanol, than
      African third chromosomes, suggesting that the higher ethanol resistance
      conferred by the former might be due to increased resistance to deleterious
      effects of ethanol-derived acetic acid. In support of this hypothesis, when
      ethanol catabolism was blocked with an Alcohol dehydrogenase mutant, there was no
      difference in ethanol resistance between flies with European and African third
      chromosomes. 

PMID- 25392460
TI  - Do greater mouse-eared bats experience a trade-off between energy conservation
      and learning?
AB  - Bats, some species of rodents and some birds are able to save energy during the
      summer period by decreasing their body temperature and falling into torpor. Some
      studies indicate that torpor prevents sleeping and causes effects similar to
      sleep deprivation. Impairment of processes stabilizing memory slows down learning
      accuracy and speed. We conducted two experiments to test whether greater mouse
      eared bats, Myotis myotis, which commonly use torpor during the summer period,
      experience a trade-off between energy savings and learning abilities. We compared
      learning speed and accuracy in bats that were exposed to low (7 degrees C) and
      higher ambient temperatures (22 degrees C) between training and experimental
      sessions. Tests were conducted in experiments with food reward (food search) and
      without food reward (perch search). Time spent with the skin temperature above 30
      degrees C was significantly longer for bats exposed to 22 degrees C than for
      those exposed to 7 degrees C, and longer in experiments with food reward than
      without food reward. We observed only a very weak tendency for better accuracy
      and shorter search times in bats exposed to 22 degrees C than in those exposed to
      7 degrees C. Our data indicate that memory consolidation of bats under natural
      conditions is not affected by daily torpor when bats are in good condition and
      may therefore defend against a rapid fall into torpor. We suggest that
      homeostatic processes connected with the circadian rhythm allow protection of the
      consolidation of memory for relatively simple tasks despite time spent in torpor.

PMID- 25392461
TI  - Gravity anomalies without geomagnetic disturbances interfere with pigeon homing-
      a GPS tracking study.
AB  - The gravity vector theory postulates that birds determine their position to set a
      home course by comparing the memorized gravity vector at the home loft with the
      local gravity vector at the release site, and that they should adjust their
      flight course to the gravity anomalies encountered. As gravity anomalies are
      often intermingled with geomagnetic anomalies, we released experienced pigeons
      from the center of a strong circular gravity anomaly (25 km diameter) not
      associated with magnetic anomalies and from a geophysical control site,
      equidistant from the home loft (91 km). After crossing the border zone of the
      anomaly--expected to be most critical for pigeon navigation--they dispersed
      significantly more than control birds, except for those having met a gravity
      anomaly en route. These data increase the credibility of the gravity vector
      hypothesis.

PMID- 25392462
TI  - Response to "The impact of modern treatment principles may have eliminated
      lithium-induced renal failure" Aiff et al. 2014.

PMID- 25392463
TI  - Reply to letter to the editor.

PMID- 25392464
TI  - Reactive vaccination in the presence of disease hotspots.
AB  - Reactive vaccination has recently been adopted as an outbreak response tool for
      cholera and other infectious diseases. Owing to the global shortage of oral
      cholera vaccine, health officials must quickly decide who and where to distribute
      limited vaccine. Targeted vaccination in transmission hotspots (i.e. areas with
      high transmission efficiency) may be a potential approach to efficiently allocate
      vaccine, however its effectiveness will likely be context-dependent. We compared
      strategies for allocating vaccine across multiple areas with heterogeneous
      transmission efficiency. We constructed metapopulation models of a cholera-like
      disease and compared simulated epidemics where: vaccine is targeted at areas of
      high or low transmission efficiency, where vaccine is distributed across the
      population, and where no vaccine is used. We find that connectivity between
      populations, transmission efficiency, vaccination timing and the amount of
      vaccine available all shape the performance of different allocation strategies.
      In highly connected settings (e.g. cities) when vaccinating early in the
      epidemic, targeting limited vaccine at transmission hotspots is often optimal.
      Once vaccination is delayed, targeting the hotspot is rarely optimal, and
      strategies that either spread vaccine between areas or those targeted at non
      hotspots will avert more cases. Although hotspots may be an intuitive outbreak
      control target, we show that, in many situations, the hotspot-epidemic proceeds
      so fast that hotspot-targeted reactive vaccination will prevent relatively few
      cases, and vaccination shared across areas where transmission can be sustained is
      often best. 

PMID- 25392465
TI  - Eyespots deflect predator attack increasing fitness and promoting the evolution
      of phenotypic plasticity.
AB  - Some eyespots are thought to deflect attack away from the vulnerable body, yet
      there is limited empirical evidence for this function and its adaptive advantage.
      Here, we demonstrate the conspicuous ventral hindwing eyespots found on Bicyclus
      anynana butterflies protect against invertebrate predators, specifically praying
      mantids. Wet season (WS) butterflies with larger, brighter eyespots were easier
      for mantids to detect, but more difficult to capture compared to dry season (DS)
      butterflies with small, dull eyespots. Mantids attacked the wing eyespots of WS
      butterflies more frequently resulting in greater butterfly survival and
      reproductive success. With a reciprocal eyespot transplant, we demonstrated the
      fitness benefits of eyespots were independent of butterfly behaviour. Regardless
      of whether the butterfly was WS or DS, large marginal eyespots pasted on the
      hindwings increased butterfly survival and successful oviposition during
      predation encounters. In previous studies, DS B. anynana experienced delayed
      detection by vertebrate predators, but both forms suffered low survival once
      detected. Our results suggest predator abundance, identity and phenology may all
      be important selective forces for B. anynana. Thus, reciprocal selection between
      invertebrate and vertebrate predators across seasons may contribute to the
      evolution of the B. anynana polyphenism. 

PMID- 25392467
TI  - Parental risk management in relation to offspring defence: bad news for kids.
AB  - Do parents defend their offspring whenever necessary, and do self-sacrificing
      parents really exist? Studies recognized that parent defence is dynamic, mainly
      depending on the threat predators pose. In this context, parental risk management
      should consider the threat to themselves and to their offspring. Consequently,
      the observed defence should be a composite of both risk components. Surprisingly,
      no study so far has determined the influence of these two threat components on
      parental decision rules. In a field experiment, we investigated parental risk
      taking in relation to the threat posed to themselves and their offspring. To
      disentangle the two threat components, we examined defence behaviours of parent
      blue tits Cyanistes caeruleus towards three different predators and during
      different nestling developmental stages. Nest defence strategies in terms of
      alarm call intensity and nearest predator approach differed between the three
      predators. Defence intensity was only partly explained by threat level. Most
      importantly, parental risk management varied in relation to their own, but not
      offspring risk. Parent defence investment was independent of nestling risk when
      parents followed a high-risk strategy. However, parents considered nestling as
      well as parental risk when following a low-risk strategy. Our findings could have
      general implications for the economy of risk management and decision-making
      strategies in living beings, including humans. 

PMID- 25392466
TI  - Serial infection of diverse host (Mus) genotypes rapidly impedes pathogen fitness
      and virulence.
AB  - Reduced genetic variation among hosts may favour the emergence of virulent
      infectious diseases by enhancing pathogen replication and its associated
      virulence due to adaptation to a limited set of host genotypes. Here, we test
      this hypothesis using experimental evolution of a mouse-specific retroviral
      pathogen, Friend virus (FV) complex. We demonstrate rapid fitness (i.e. viral
      titre) and virulence increases when FV complex serially infects a series of
      inbred mice representing the same genotype, but not when infecting a diverse
      array of inbred mouse strains modelling the diversity in natural host
      populations. Additionally, a single infection of a different host genotype was
      sufficient to constrain the emergence of a high fitness/high virulence FV complex
      phenotype in these experiments. The potent inhibition of viral fitness and
      virulence was associated with an observed loss of the defective retroviral genome
      (spleen focus-forming virus), whose presence exacerbates infection and drives
      disease in susceptible mice. Results from our experiments provide an important
      first step in understanding how genetic variation among vertebrate hosts
      influences pathogen evolution and suggests that serial exposure to different
      genotypes within a single host species may act as a constraint on pathogen
      adaptation that prohibits the emergence of more virulent infections. From a
      practical perspective, these results have implications for low-diversity host
      populations such as endangered species and domestic animals. 

PMID- 25392468
TI  - Direct and indirect causal effects of heterozygosity on fitness-related traits in
      Alpine ibex.
AB  - Heterozygosity-fitness correlations (HFCs) are a useful tool to investigate the
      effects of inbreeding in wild populations, but are not informative in
      distinguishing between direct and indirect effects of heterozygosity on fitness
      related traits. We tested HFCs in male Alpine ibex (Capra ibex) in a free-ranging
      population (which suffered a severe bottleneck at the end of the eighteenth
      century) and used confirmatory path analysis to disentangle the causal
      relationships between heterozygosity and fitness-related traits. We tested HFCs
      in 149 male individuals born between 1985 and 2009. We found that standardized
      multi-locus heterozygosity (MLH), calculated from 37 microsatellite loci, was
      related to body mass and horn growth, which are known to be important fitness
      related traits, and to faecal egg counts (FECs) of nematode eggs, a proxy of
      parasite resistance. Then, using confirmatory path analysis, we were able to show
      that the effect of MLH on horn growth was not direct but mediated by body mass
      and FEC. HFCs do not necessarily imply direct genetic effects on fitness-related
      traits, which instead can be mediated by other traits in complex and unexpected
      ways. 

PMID- 25392469
TI  - The relative importance of direct and indirect effects of hunting mortality on
      the population dynamics of brown bears.
AB  - There is increasing evidence of indirect effects of hunting on populations. In
      species with sexually selected infanticide (SSI), hunting may decrease juvenile
      survival by increasing male turnover. We aimed to evaluate the relative
      importance of direct and indirect effects of hunting via SSI on the population
      dynamics of the Scandinavian brown bear (Ursus arctos). We performed prospective
      and retrospective demographic perturbation analyses for periods with low and high
      hunting pressures. All demographic rates, except yearling survival, were lower
      under high hunting pressure, which led to a decline in population growth under
      high hunting pressure (lambda = 0.975; 95% CI = 0.914-1.011). Hunting had
      negative indirect effects on the population through an increase in SSI, which
      lowered cub survival and possibly also fecundity rates. Our study suggests that
      SSI could explain 13.6% of the variation in population growth. Hunting also
      affected the relative importance of survival and fecundity of adult females for
      population growth, with fecundity being more important under low hunting pressure
      and survival more important under high hunting pressure. Our study sheds light on
      the importance of direct and indirect effects of hunting on population dynamics,
      and supports the contention that hunting can have indirect negative effects on
      populations through SSI. 

PMID- 25392470
TI  - On the origin of sex chromosomes from meiotic drive.
AB  - Most animals and many plants make use of specialized chromosomes (sex
      chromosomes) to determine an individual's sex. Best known are the XY and ZW sex
      determination systems. Despite having evolved numerous times, sex chromosomes
      present something of an evolutionary puzzle. At their origin, alleles that
      dictate development as one sex or the other (primitive sex chromosomes) face a
      selective penalty, as they will be found more often in the more abundant sex. How
      is it possible that primitive sex chromosomes overcome this disadvantage? Any
      theory for the origin of sex chromosomes must identify the benefit that outweighs
      this cost and enables a sex-determining mutation to establish in the population.
      Here we show that a new sex-determining allele succeeds when linked to a sex
      specific meiotic driver. The new sex-determining allele benefits from confining
      the driving allele to the sex in which it gains the benefit of drive. Our model
      requires few special assumptions and is sufficiently general to apply to the
      evolution of sex chromosomes in outbreeding cosexual or dioecious species. We
      highlight predictions of the model that can discriminate between this and
      previous theories of sex-chromosome origins. 

PMID- 25392471
TI  - Loss of animal seed dispersal increases extinction risk in a tropical tree
      species due to pervasive negative density dependence across life stages.
AB  - Overhunting in tropical forests reduces populations of vertebrate seed
      dispersers. If reduced seed dispersal has a negative impact on tree population
      viability, overhunting could lead to altered forest structure and dynamics,
      including decreased biodiversity. However, empirical data showing decreased
      animal-dispersed tree abundance in overhunted forests contradict demographic
      models which predict minimal sensitivity of tree population growth rate to early
      life stages. One resolution to this discrepancy is that seed dispersal determines
      spatial aggregation, which could have demographic consequences for all life
      stages. We tested the impact of dispersal loss on population viability of a
      tropical tree species, Miliusa horsfieldii, currently dispersed by an intact
      community of large mammals in a Thai forest. We evaluated the effect of spatial
      aggregation for all tree life stages, from seeds to adult trees, and constructed
      simulation models to compare population viability with and without animal
      mediated seed dispersal. In simulated populations, disperser loss increased
      spatial aggregation by fourfold, leading to increased negative density dependence
      across the life cycle and a 10-fold increase in the probability of extinction.
      Given that the majority of tree species in tropical forests are animal-dispersed,
      overhunting will potentially result in forests that are fundamentally different
      from those existing now. 

PMID- 25392472
TI  - Active foraging for toxic prey during gestation in a snake with maternal
      provisioning of sequestered chemical defences.
AB  - Many animals sequester dietary defensive compounds and incorporate them into the
      offspring, which protects the young against predation. One possible but poorly
      investigated question is whether females of such species actively prey upon toxic
      diets. The snake Rhabdophis tigrinus sequesters defensive steroids from toads
      consumed as prey; it also feeds on other amphibians. Females produce chemically
      armed offspring in direct proportion to their own level of toad-derived toxins by
      provisioning the toxins to their eggs. Our field observations of movements and
      stomach contents of radio-tracked R. tigrinus showed that gravid snakes preyed
      upon toads by actively foraging in the habitat of toads, even though toads were a
      scarce resource and toad-searching may incur potential costs. Our Y-maze
      experiments demonstrated that gravid females were more likely to trail the
      chemical cues of toads than were males or non-gravid females. These results
      showed behavioural switching in females and active foraging for scarce, toxic
      prey during gestation. Because exploitation of toads by gravid females results in
      their offspring being more richly endowed with prey-derived toxins, active
      foraging for toxic prey is expected to be an adaptive antipredator trait, which
      may enhance chemical defence in offspring. 

PMID- 25392473
TI  - Higher frequency of social learning in China than in the West shows cultural
      variation in the dynamics of cultural evolution.
AB  - Cultural evolutionary models have identified a range of conditions under which
      social learning (copying others) is predicted to be adaptive relative to asocial
      learning (learning on one's own), particularly in humans where socially learned
      information can accumulate over successive generations. However, cultural
      evolution and behavioural economics experiments have consistently shown
      apparently maladaptive under-utilization of social information in Western
      populations. Here we provide experimental evidence of cultural variation in
      people's use of social learning, potentially explaining this mismatch. People in
      mainland China showed significantly more social learning than British people in
      an artefact-design task designed to assess the adaptiveness of social information
      use. People in Hong Kong, and Chinese immigrants in the UK, resembled British
      people in their social information use, suggesting a recent shift in these groups
      from social to asocial learning due to exposure to Western culture. Finally,
      Chinese mainland participants responded less than other participants to increased
      environmental change within the task. Our results suggest that learning
      strategies in humans are culturally variable and not genetically fixed,
      necessitating the study of the 'social learning of social learning strategies'
      whereby the dynamics of cultural evolution are responsive to social processes,
      such as migration, education and globalization. 

PMID- 25392474
TI  - Ecological dynamics of emerging bat virus spillover.
AB  - Viruses that originate in bats may be the most notorious emerging zoonoses that
      spill over from wildlife into domestic animals and humans. Understanding how
      these infections filter through ecological systems to cause disease in humans is
      of profound importance to public health. Transmission of viruses from bats to
      humans requires a hierarchy of enabling conditions that connect the distribution
      of reservoir hosts, viral infection within these hosts, and exposure and
      susceptibility of recipient hosts. For many emerging bat viruses, spillover also
      requires viral shedding from bats, and survival of the virus in the environment.
      Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg
      virus and coronaviruses, we delineate this cross-species spillover dynamic from
      the within-host processes that drive virus excretion to land-use changes that
      increase interaction among species. We describe how land-use changes may affect
      co-occurrence and contact between bats and recipient hosts. Two hypotheses may
      explain temporal and spatial pulses of virus shedding in bat populations:
      episodic shedding from persistently infected bats or transient epidemics that
      occur as virus is transmitted among bat populations. Management of livestock also
      may affect the probability of exposure and disease. Interventions to decrease the
      probability of virus spillover can be implemented at multiple levels from
      targeting the reservoir host to managing recipient host exposure and
      susceptibility. 

PMID- 25392476
TI  - The contribution of additive genetic variation to personality variation:
      heritability of personality.
AB  - Individual animals frequently exhibit repeatable differences from other members
      of their population, differences now commonly referred to as 'animal
      personality'. Personality differences can arise, for example, from differences in
      permanent environmental effects--including parental and epigenetic contributors-
      and the effect of additive genetic variation. Although several studies have
      evaluated the heritability of behaviour, less is known about general patterns of
      heritability and additive genetic variation in animal personality. As overall
      variation in behaviour includes both the among-individual differences that
      reflect different personalities and temporary environmental effects, it is
      possible for personality to be largely genetically influenced even when
      heritability of behaviour per se is quite low. The relative contribution of
      additive genetic variation to personality variation can be estimated whenever
      both repeatability and heritability are estimated for the same data. Using
      published estimates to address this issue, we found that approximately 52% of
      animal personality variation was attributable to additive genetic variation.
      Thus, while the heritability of behaviour is often moderate or low, the
      heritability of personality is much higher. Our results therefore (i) demonstrate
      that genetic differences are likely to be a major contributor to variation in
      animal personality and (ii) support the phenotypic gambit: that evolutionary
      inferences drawn from repeatability estimates may often be justified.

PMID- 25392475
TI  - Secondary contact seeds phenotypic novelty in cichlid fishes.
AB  - Theory proposes that genomic admixture between formerly reproductively isolated
      populations can generate phenotypic novelty for selection to act upon. Secondary
      contact may therefore be a significant promoter of phenotypic novelty that allows
      species to overcome environmental challenges and adapt to novel environments,
      including during adaptive radiation. To date, this has largely been considered
      from the perspective of interspecific hybridization at contact zones. However, it
      is also possible that this process occurs more commonly between natural
      populations of a single species, and thus its importance in adaptive evolution
      may have been underestimated. In this study, we tested the consequences of
      genomic introgression during apparent secondary contact between phenotypically
      similar lineages of the riverine cichlid fish Astatotilapia calliptera. We
      provide population genetic evidence of a secondary contact zone in the wild, and
      then demonstrate using mate-choice experiments that both lineages can reproduce
      together successfully in laboratory conditions. Finally, we show that genomically
      admixed individuals display extreme phenotypes not observed in the parental
      lineages. Collectively, the evidence shows that secondary contact can drive the
      evolution of phenotypic novelty, suggesting that pulses of secondary contact may
      repeatedly seed genetic novelty, which when coupled with ecological opportunity
      could promote rapid adaptive evolution in natural circumstances. 

PMID- 25392477
TI  - Predator-induced phenotypic plasticity within- and across-generations: a
      challenge for theory?
AB  - Much work has shown that the environment can induce non-genetic changes in
      phenotype that span multiple generations. Theory predicts that predictable
      environmental variation selects for both increased within- and across-generation
      responses. Yet, to the best of our knowledge, there are no empirical tests of
      this prediction. We explored the relationship between within- versus across
      generation plasticity by evaluating the influence of predator cues on the life
      history traits of Daphnia ambigua. We measured the duration of predator-induced
      transgenerational effects, determined when transgenerational responses are
      induced, and quantified the cues that activate transgenerational plasticity. We
      show that predator exposure during embryonic development causes earlier
      maturation and increased reproductive output. Such effects are detectable two
      generations removed from predator exposure and are similar in magnitude in
      response to exposure to cues emitted by injured conspecifics. Moreover, all
      experimental contexts and traits yielded a negative correlation between within-
      versus across-generation responses. That is, responses to predator cues within-
      and across-generations were opposite in sign and magnitude. Although many models
      address transgenerational plasticity, none of them explain this apparent negative
      relationship between within- and across-generation plasticities. Our results
      highlight the need to refine the theory of transgenerational plasticity. 

PMID- 25392478
TI  - Complementation of the embryo-lethal T-DNA insertion mutant of AUXIN-BINDING
      PROTEIN 1 (ABP1) with abp1 point mutated versions reveals crosstalk of ABP1 and
      phytochromes.
AB  - The function of the extracytoplasmic AUXIN-BINDING-PROTEIN1 (ABP1) is largely
      enigmatic. We complemented a homozygous T-DNA insertion null mutant of ABP1 in
      Arabidopsis thaliana Wassilewskia with three mutated and one wild-type (wt) ABP1
      cDNA, all tagged C-terminally with a strepII-FLAG tag upstream the KDEL signal.
      Based on in silico modelling, the abp1 mutants were predicted to have altered
      geometries of the auxin binding pocket and calculated auxin binding energies
      lower than the wt. Phenotypes linked to auxin transport were compromised in these
      three complemented abp1 mutants. Red light effects, such as elongation of
      hypocotyls in constant red (R) and far-red (FR) light, in white light
      supplemented by FR light simulating shade, and inhibition of gravitropism by R or
      FR, were all compromised in the complemented lines. Using auxin- or light-induced
      expression of marker genes, we showed that auxin-induced expression was delayed
      already after 10 min, and light-induced expression within 60 min, even though
      TIR1/AFB or phyB are thought to act as receptors relevant for gene expression
      regulation. The expression of marker genes in seedlings responding to both auxin
      and shade showed that for both stimuli regulation of marker gene expression was
      altered after 10-20 min in the wild type and phyB mutant. The rapidity of
      expression responses provides a framework for the mechanics of functional
      interaction of ABP1 and phyB to trigger interwoven signalling pathways.

PMID- 25392480
TI  - The effects of aging on substantia nigra dopamine neurons.

PMID- 25392479
TI  - Ectopic overexpression of the cell wall invertase gene CIN1 leads to dehydration
      avoidance in tomato.
AB  - Drought stress conditions modify source-sink relations, thereby influencing plant
      growth, adaptive responses, and consequently crop yield. Invertases are key
      metabolic enzymes regulating sink activity through the hydrolytic cleavage of
      sucrose into hexose monomers, thus playing a crucial role in plant growth and
      development. However, the physiological role of invertases during adaptation to
      abiotic stress conditions is not yet fully understood. Here it is shown that
      plant adaptation to drought stress can be markedly improved in tomato (Solanum
      lycopersicum L.) by overexpression of the cell wall invertase (cwInv) gene CIN1
      from Chenopodium rubrum. CIN1 overexpression limited stomatal conductance under
      normal watering regimes, leading to reduced water consumption during the drought
      period, while photosynthetic activity was maintained. This caused a strong
      increase in water use efficiency (up to 50%), markedly improving water stress
      adaptation through an efficient physiological strategy of dehydration avoidance.
      Drought stress strongly reduced cwInv activity and induced its proteinaceous
      inhibitor in the leaves of the wild-type plants. However, the CIN1-overexpressing
      plants registered 3- to 6-fold higher cwInv activity in all analysed conditions.
      Surprisingly, the enhanced invertase activity did not result in increased hexose
      concentrations due to the activation of the metabolic carbohydrate fluxes, as
      reflected by the maintenance of the activity of key enzymes of primary metabolism
      and increased levels of sugar-phosphate intermediates under water deprivation.
      The induced sink metabolism in the leaves explained the maintenance of
      photosynthetic activity, delayed senescence, and increased source activity under
      drought stress. Moreover, CIN1 plants also presented a better control of
      production of reactive oxygen species and sustained membrane protection. Those
      metabolic changes conferred by CIN1 overexpression were accompanied by increases
      in the concentrations of the senescence-delaying hormone trans-zeatin and
      decreases in the senescence-inducing ethylene precursor 1-aminocyclopropane-1
      carboxylic acid (ACC) in the leaves. Thus, cwInv critically functions at the
      integration point of metabolic, hormonal, and stress signals, providing a novel
      strategy to overcome drought-induced limitations to crop yield, without
      negatively affecting plant fitness under optimal growth conditions. 

PMID- 25392481
TI  - Auditory cortical processing in real-world listening: the auditory system going
      real.
AB  - The auditory sense of humans transforms intrinsically senseless pressure
      waveforms into spectacularly rich perceptual phenomena: the music of Bach or the
      Beatles, the poetry of Li Bai or Omar Khayyam, or more prosaically the sense of
      the world filled with objects emitting sounds that is so important for those of
      us lucky enough to have hearing. Whereas the early representations of sounds in
      the auditory system are based on their physical structure, higher auditory
      centers are thought to represent sounds in terms of their perceptual attributes.
      In this symposium, we will illustrate the current research into this process,
      using four case studies. We will illustrate how the spectral and temporal
      properties of sounds are used to bind together, segregate, categorize, and
      interpret sound patterns on their way to acquire meaning, with important lessons
      to other sensory systems as well. 

PMID- 25392482
TI  - Exercise, energy intake, glucose homeostasis, and the brain.
AB  - Here we summarize topics covered in an SFN symposium that considered how and why
      exercise and energy intake affect neuroplasticity and, conversely, how the brain
      regulates peripheral energy metabolism. This article is not a comprehensive
      review of the subject, but rather a view of how the authors' findings fit into a
      broader context. Emerging findings elucidate cellular and molecular mechanisms by
      which exercise and energy intake modify the plasticity of neural circuits in ways
      that affect brain health. By enhancing neurogenesis, synaptic plasticity and
      neuronal stress robustness, exercise and intermittent energy restriction/fasting
      may optimize brain function and forestall metabolic and neurodegenerative
      diseases. Moreover, brain-centered glucoregulatory and immunomodulating systems
      that mediate peripheral health benefits of intermittent energetic challenges have
      recently been described. A better understanding of adaptive neural response
      pathways activated by energetic challenges will enable the development and
      optimization of interventions to reduce the burden of disease in our communities.

PMID- 25392483
TI  - Baths salts, spice, and related designer drugs: the science behind the headlines.
AB  - The abuse of synthetic psychoactive substances known as "designer drugs," or "new
      psychoactive substances" (NPS), is increasing at an alarming rate. NPS are
      purchased as alternatives to traditional illicit drugs of abuse and are
      manufactured to circumvent laws regulating the sale and use of controlled
      substances. Synthetic cathinones (i.e., "bath salts") and synthetic cannabinoids
      (i.e., "spice") are two types of NPS that have received substantial media
      attention. Although low recreational doses of bath salts or spice compounds can
      produce desirable effects, high doses or chronic exposure often leads to
      dangerous medical consequences, including psychosis, violent behaviors,
      tachycardia, hyperthermia, and even death. Despite the popularity of NPS, there
      is a paucity of scientific data about these drugs. Here we provide a brief up-to
      date review describing the mechanisms of action and neurobiological effects of
      synthetic cathinones and cannabinoids. 

PMID- 25392484
TI  - More than a pore: ion channel signaling complexes.
AB  - Voltage- and ligand-gated ion channels form the molecular basis of cellular
      excitability. With >400 members and accounting for ~1.5% of the human genome, ion
      channels are some of the most well studied of all proteins in heterologous
      expression systems. Yet, ion channels often exhibit unexpected properties in vivo
      because of their interaction with a variety of signaling/scaffolding proteins.
      Such interactions can influence the function and localization of ion channels, as
      well as their coupling to intracellular second messengers and pathways, thus
      increasing the signaling potential of these ion channels in neurons. Moreover,
      functions have been ascribed to ion channels that are largely independent of
      their ion-conducting roles. Molecular and functional dissection of the ion
      channel proteome/interactome has yielded new insights into the composition of ion
      channel complexes and how their dysregulation leads to human disease. 

PMID- 25392485
TI  - Novel RNA modifications in the nervous system: form and function.
AB  - Modified RNA molecules have recently been shown to regulate nervous system
      functions. This mini-review and associated mini-symposium provide an overview of
      the types and known functions of novel modified RNAs in the nervous system,
      including covalently modified RNAs, edited RNAs, and circular RNAs. We discuss
      basic molecular mechanisms involving RNA modifications as well as the impact of
      modified RNAs and their regulation on neuronal processes and disorders, including
      neural fate specification, intellectual disability, neurodegeneration, dopamine
      neuron function, and substance use disorders. 

PMID- 25392486
TI  - New roles for the external globus pallidus in basal ganglia circuits and
      behavior.
AB  - The development of methodology to identify specific cell populations and circuits
      within the basal ganglia is rapidly transforming our ability to understand the
      function of this complex circuit. This mini-symposium highlights recent advances
      in delineating the organization and function of neural circuits in the external
      segment of the globus pallidus (GPe). Although long considered a homogeneous
      structure in the motor-suppressing "indirect-pathway," the GPe consists of a
      number of distinct cell types and anatomical subdomains that contribute
      differentially to both motor and nonmotor features of behavior. Here, we
      integrate recent studies using techniques, such as viral tracing, transgenic
      mice, electrophysiology, and behavioral approaches, to create a revised framework
      for understanding how the GPe relates to behavior in both health and disease. 

PMID- 25392487
TI  - A lipid gate for the peripheral control of pain.
AB  - Cells in injured and inflamed tissues produce a number of proalgesic lipid
      derived mediators, which excite nociceptive neurons by activating selective G
      protein-coupled receptors or ligand-gated ion channels. Recent work has shown
      that these proalgesic factors are counteracted by a distinct group of lipid
      molecules that lower nociceptor excitability and attenuate nociception in
      peripheral tissues. Analgesic lipid mediators include endogenous agonists of
      cannabinoid receptors (endocannabinoids), lipid-amide agonists of peroxisome
      proliferator-activated receptor-alpha, and products of oxidative metabolism of
      polyunsaturated fatty acids via cytochrome P450 and other enzyme pathways.
      Evidence indicates that these lipid messengers are produced and act at different
      stages of inflammation and the response to tissue injury, and may be part of a
      peripheral gating mechanism that regulates the access of nociceptive information
      to the spinal cord and the brain. Growing knowledge about this peripheral control
      system may be used to discover safer medicines for pain. 

PMID- 25392488
TI  - Network-mediated encoding of circadian time: the suprachiasmatic nucleus (SCN)
      from genes to neurons to circuits, and back.
AB  - The transcriptional architecture of intracellular circadian clocks is similar
      across phyla, but in mammals interneuronal mechanisms confer a higher level of
      circadian integration. The suprachiasmatic nucleus (SCN) is a unique model to
      study these mechanisms, as it operates as a ~24 h clock not only in the living
      animal, but also when isolated in culture. This "clock in a dish" can be used to
      address fundamental questions, such as how intraneuronal mechanisms are
      translated by SCN neurons into circuit-level emergent properties and how the
      circuit decodes, and responds to, light input. This review addresses recent
      developments in understanding the relationship between electrical activity,
      [Ca(2+)]i, and intracellular clocks. Furthermore, optogenetic and chemogenetic
      approaches to investigate the distinct roles of neurons and glial cells in
      circuit encoding of circadian time will be discussed, as well as the epigenetic
      and circuit-level mechanisms that enable the SCN to translate light input into
      coherent daily rhythms. 

PMID- 25392489
TI  - Endothelial dysfunction abrogates the efficacy of normobaric hyperoxia in stroke.
AB  - Hyperoxia has been uniformly efficacious in experimental focal cerebral ischemia.
      However, pilot clinical trials have showed mixed results slowing its translation
      in patient care. To explain the discordance between experimental and clinical
      outcomes, we tested the impact of endothelial dysfunction, exceedingly common in
      stroke patients but under-represented in experimental studies, on the
      neuroprotective efficacy of normobaric hyperoxia. We used hyperlipidemic
      apolipoprotein E knock-out and endothelial nitric oxide synthase knock-out mice
      as models of endothelial dysfunction, and examined the effects of normobaric
      hyperoxia on tissue perfusion and oxygenation using high-resolution combined
      laser speckle and multispectral reflectance imaging during distal middle cerebral
      artery occlusion. In normal wild-type mice, normobaric hyperoxia rapidly and
      significantly improved tissue perfusion and oxygenation, suppressed peri-infarct
      depolarizations, reduced infarct volumes, and improved neurological function. In
      contrast, normobaric hyperoxia worsened perfusion in ischemic brain and failed to
      reduce infarct volumes or improve neurological function in mice with endothelial
      dysfunction. These data suggest that the beneficial effects of hyperoxia on
      ischemic tissue oxygenation, perfusion, and outcome are critically dependent on
      endothelial nitric oxide synthase function. Therefore, vascular risk factors
      associated with endothelial dysfunction may predict normobaric hyperoxia
      nonresponders in ischemic stroke. These data may have implications for myocardial
      and systemic circulation as well. 

PMID- 25392491
TI  - Neurogenin3 restricts serotonergic neuron differentiation to the hindbrain.
AB  - The development of the nervous system is critically dependent on the production
      of functionally diverse neuronal cell types at their correct locations. In the
      embryonic neural tube, dorsoventral signaling has emerged as a fundamental
      mechanism for generating neuronal diversity. In contrast, far less is known about
      how different neuronal cell types are organized along the rostrocaudal axis. In
      the developing mouse and chick neural tube, hindbrain serotonergic neurons and
      spinal glutamatergic V3 interneurons are produced from ventral p3 progenitors,
      which possess a common transcriptional identity but are confined to distinct
      anterior-posterior territories. In this study, we show that the expression of the
      transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the
      correct specification of p3-derived neurons. Gain- and loss-of-function
      manipulations in the chick and mouse embryo show that Neurog3 switches ventral
      progenitors from a serotonergic to V3 differentiation program by repressing Ascl1
      in spinal p3 progenitors through a mechanism dependent on Hes proteins. In this
      way, Neurog3 establishes the posterior boundary of the serotonergic system by
      actively suppressing serotonergic specification in the spinal cord. These results
      explain how equivalent p3 progenitors within the hindbrain and the spinal cord
      produce functionally distinct neuron cell types. 

PMID- 25392490
TI  - Excitatory effects of parvalbumin-expressing interneurons maintain hippocampal
      epileptiform activity via synchronous afterdischarges.
AB  - Epileptic seizures are characterized by periods of hypersynchronous,
      hyperexcitability within brain networks. Most seizures involve two stages: an
      initial tonic phase, followed by a longer clonic phase that is characterized by
      rhythmic bouts of synchronized network activity called afterdischarges (ADs).
      Here we investigate the cellular and network mechanisms underlying hippocampal
      ADs in an effort to understand how they maintain seizure activity. Using in vitro
      hippocampal slice models from rats and mice, we performed electrophysiological
      recordings from CA3 pyramidal neurons to monitor network activity and changes in
      GABAergic signaling during epileptiform activity. First, we show that the highest
      synchrony occurs during clonic ADs, consistent with the idea that specific
      circuit dynamics underlie this phase of the epileptiform activity. We then show
      that ADs require intact GABAergic synaptic transmission, which becomes excitatory
      as a result of a transient collapse in the chloride (Cl(-)) reversal potential.
      The depolarizing effects of GABA are strongest at the soma of pyramidal neurons,
      which implicates somatic-targeting interneurons in AD activity. To test this, we
      used optogenetic techniques to selectively control the activity of somatic
      targeting parvalbumin-expressing (PV(+)) interneurons. Channelrhodopsin-2
      mediated activation of PV(+) interneurons during the clonic phase generated
      excitatory GABAergic responses in pyramidal neurons, which were sufficient to
      elicit and entrain synchronous AD activity across the network. Finally,
      archaerhodopsin-mediated selective silencing of PV(+) interneurons reduced the
      occurrence of ADs during the clonic phase. Therefore, we propose that activity
      dependent Cl(-) accumulation subverts the actions of PV(+) interneurons to
      perpetuate rather than terminate pathological network hyperexcitability during
      the clonic phase of seizures. 

PMID- 25392492
TI  - Noradrenergic plasticity of olfactory sensory neuron inputs to the main olfactory
      bulb.
AB  - Sensory responses are modulated by internal factors including attention,
      experience, and brain state. This is partly due to fluctuations in
      neuromodulatory input from regions such as the noradrenergic locus ceruleus (LC)
      in the brainstem. LC activity changes with arousal and modulates sensory
      processing, cognition, and memory. The main olfactory bulb (MOB) is richly
      targeted by LC fibers and noradrenaline profoundly influences MOB circuitry and
      odor-guided behavior. Noradrenaline-dependent plasticity affects the output of
      the MOB; however. it is unclear whether noradrenergic plasticity also affects the
      input to the MOB from olfactory sensory neurons (OSNs) in the glomerular layer.
      Noradrenergic terminals are found in the glomerular layer, but noradrenaline
      receptors do not seem to acutely modulate OSN terminals in vitro. We investigated
      whether noradrenaline induces plasticity at the glomerulus. We used wide-field
      optical imaging to measure changes in odor responses following electrical
      stimulation of LC in anesthetized mice. Surprisingly, odor-evoked intrinsic
      optical signals at the glomerulus were persistently weakened after LC activation.
      Calcium imaging selectively from OSNs confirmed that this effect was due to
      suppression of presynaptic input and was prevented by noradrenergic antagonists.
      Finally, suppression of responses to an odor did not require precise coincidence
      of the odor with LC activation. However, suppression was intensified by LC
      activation in the absence of odors. We conclude that noradrenaline release from
      LC has persistent effects on odor processing already at the first synapse of the
      main olfactory system. This mechanism could contribute to arousal-dependent
      memories. 

PMID- 25392493
TI  - Reversible behavioral phenotypes in a conditional mouse model of TDP-43
      proteinopathies.
AB  - Transactive response DNA-binding protein 43 (TDP-43) mislocalization and
      aggregation are hallmark features of amyotrophic lateral sclerosis and
      frontotemporal dementia (FTD). We have previously shown in mice that inducible
      overexpression of a cytoplasmically localized form of TDP-43 (TDP-43-DeltaNLS) in
      forebrain neurons evokes neuropathological changes that recapitulate several
      features of TDP-43 proteinopathies. Detailed behavioral phenotyping could provide
      further validation for its usage as a model for FTD. In the present study, we
      performed a battery of behavioral tests to evaluate motor, cognitive, and social
      phenotypes in this model. We found that transgene (Tg) induction by doxycycline
      removal at weaning led to motor abnormalities including hyperlocomotion in the
      open field test, impaired coordination and balance in the rotarod test, and
      increased spasticity as shown by a clasping phenotype. Cognitive assessment
      demonstrated impaired recognition and spatial memory, measured by novel object
      recognition and Y-maze tests. Remarkably, TDP-43-DeltaNLS mice displayed deficits
      in social behavior, mimicking a key aspect of FTD. To determine whether these
      symptoms were reversible, we suppressed Tg expression for 14 d in 1.5-month-old
      mice showing an established behavioral phenotype but modest neurodegeneration and
      found that motor and cognitive deficits were ameliorated; however, social
      performance remained altered. When Tg expression was suppressed in 6.5-month-old
      mice showing overt neurodegeneration, motor deficits were irreversible. These
      results indicate that TDP-43-DeltaNLS mice display several core behavioral
      features of FTD with motor neuron disease, possibly due to functional changes in
      surviving neurons, and might serve as a valuable tool to unveil the underlying
      mechanisms of this and other TDP-43 proteinopathies. 

PMID- 25392494
TI  - The extracellular matrix protein laminin alpha2 regulates the maturation and
      function of the blood-brain barrier.
AB  - Laminins are major constituents of the gliovascular basal lamina of the blood
      brain barrier (BBB); however, the role of laminins in BBB development remains
      unclear. Here we report that Lama2(-/-) mice, lacking expression of the laminin
      alpha2 subunit of the laminin-211 heterotrimer expressed by astrocytes and
      pericytes, have a defective BBB in which systemically circulated tracer leaks
      into the brain parenchyma. The Lama2(-/-) vascular endothelium had significant
      abnormalities, including altered integrity and composition of the endothelial
      basal lamina, inappropriate expression of embryonic vascular endothelial protein
      MECA32, substantially reduced pericyte coverage, and tight junction
      abnormalities. Additionally, astrocytic endfeet were hypertrophic and lacked
      appropriately polarized aquaporin4 channels. Laminin-211 appears to mediate these
      effects at least in part by dystroglycan receptor interactions, as preventing
      dystroglycan expression in neural cells led to a similar set of BBB abnormalities
      and gliovascular disturbances, which additionally included perturbed vascular
      endothelial glucose transporter-1 localization. These findings provide insight
      into the cell and molecular changes that occur in congenital muscular dystrophies
      caused by Lama2 mutations or inappropriate dystroglycan post-translational
      modifications, which have accompanying brain abnormalities, including seizures.
      Our results indicate a novel role for laminin-dystroglycan interactions in the
      cooperative integration of astrocytes, endothelial cells, and pericytes in
      regulating the BBB. 

PMID- 25392495
TI  - ATP13A2/PARK9 regulates secretion of exosomes and alpha-synuclein.
AB  - Kufor-Rakeb syndrome (KRS) is caused by loss-of-function mutations in ATP13A2
      (PARK9) and characterized by juvenile-onset parkinsonism, pyramidal signs, and
      cognitive decline. Previous studies suggested that PARK9 deficiency causes
      lysosomal dysfunction and alpha-synuclein (alpha-syn) accumulation, whereas PARK9
      overexpression suppresses toxicity of alpha-syn. However, the precise mechanism
      of PARK9 effect on lysosomes and alpha-syn has been unknown. Here, we found that
      overexpressed PARK9 localized to multivesicular bodies (MVBs) in the human H4
      cell line. The results from patient fibroblasts showed that loss of PARK9
      function leads to decreased number of the intraluminal vesicles in MVBs and
      diminished release of exosomes into culture media. By contrast, overexpression of
      PARK9 results in increased release of exosomes in H4 cells and mouse primary
      cortical neurons. Moreover, loss of PARK9 function resulted in decreased
      secretion of alpha-syn into extracellular space, whereas overexpressed PARK9
      promotes secretion of alpha-syn, at least in part via exosomes. Finally, we found
      that PARK9 regulates exosome biogenesis through functional interaction with the
      endosomal sorting complex required for transport machinery. Together, these data
      suggest the involvement of PARK9 in the biogenesis of exosomes and alpha-syn
      secretion and raise a possibility that disruption of these pathways in patients
      with KRS contributes to the disease pathogenesis. 

PMID- 25392497
TI  - Sexual differentiation of the brain requires perinatal kisspeptin-GnRH neuron
      signaling.
AB  - Sex differences in brain function underlie robust differences between males and
      females in both normal and disease states. Although alternative mechanisms exist,
      sexual differentiation of the male mammalian brain is initiated predominantly by
      testosterone secreted by the testes during the perinatal period. Despite
      considerable advances in understanding how testosterone and its metabolite
      estradiol sexually differentiate the brain, little is known about the mechanism
      that generates the male-specific perinatal testosterone surge. In mice, we show
      that a male-specific activation of GnRH neurons occurs 0-2 h following birth and
      that this correlates with the male-specific surge of testosterone occurring up to
      5 h after birth. The necessity of GnRH signaling for the sexually differentiating
      effects of the perinatal testosterone surge was demonstrated by the persistence
      of female-like brain characteristics in adult male, GnRH receptor knock-out mice.
      Kisspeptin neurons have recently been identified to be potent, direct activators
      of GnRH neurons. We demonstrate that a population of kisspeptin neurons appears
      in the preoptic area of only the male between E19 and P1. The importance of
      kisspeptin inputs to GnRH neurons for the process of sexual differentiation was
      demonstrated by the lack of a normal neonatal testosterone surge, and disordered
      brain sexual differentiation of male mice in which the kisspeptin receptor was
      deleted selectively from GnRH neurons. These observations demonstrate the
      necessity of perinatal GnRH signaling for driving brain sexual differentiation
      and indicate that kisspeptin inputs to GnRH neurons are essential for this
      process to occur. 

PMID- 25392496
TI  - Dnmt3a in Sim1 neurons is necessary for normal energy homeostasis.
AB  - Obesity rates continue to rise throughout the world. Recent evidence has
      suggested that environmental factors contribute to altered energy balance
      regulation. However, the role of epigenetic modifications to the central control
      of energy homeostasis remains unknown. To investigate the role of DNA methylation
      in the regulation of energy balance, we investigated the role of the de novo DNA
      methyltransferase, Dnmt3a, in Single-minded 1 (Sim1) cells, including neurons in
      the paraventricular nucleus of the hypothalamus (PVH). Dnmt3a expression levels
      were decreased in the PVH of high-fat-fed mice. Mice lacking Dnmt3a specifically
      in the Sim1 neurons, which are expressed in the forebrain, including PVH, became
      obese with increased amounts of abdominal and subcutaneous fat. The mice were
      also found to have hyperphagia, decreased energy expenditure, and glucose
      intolerance with increased serum insulin and leptin. Furthermore, these mice
      developed hyper-LDL cholesterolemia when fed a high-fat diet. Gene expression
      profiling and DNA methylation analysis revealed that the expression of tyrosine
      hydroxylase and galanin were highly upregulated in the PVH of Sim1-specific
      Dnmt3a deletion mice. DNA methylation levels of the tyrosine hydroxylase promoter
      were decreased in the PVH of the deletion mice. These results suggest that Dnmt3a
      in the PVH is necessary for the normal control of body weight and energy
      homeostasis and that tyrosine hydroxylase is a putative target of Dnmt3a in the
      PVH. These results provide evidence for a role for Dnmt3a in the PVH to link
      environmental conditions to altered energy homeostasis. 

PMID- 25392498
TI  - Control of food intake and energy expenditure by Nos1 neurons of the
      paraventricular hypothalamus.
AB  - The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous
      cluster of Sim1-expressing cell types that comprise a major autonomic output
      nucleus and play critical roles in the control of food intake and energy
      homeostasis. The roles of specific PVH neuronal subtypes in energy balance have
      yet to be defined, however. The PVH contains nitric oxide synthase-1 (Nos1)
      expressing (Nos1(PVH)) neurons of unknown function; these represent a subset of
      the larger population of Sim1-expressing PVH (Sim1(PVH)) neurons. To determine
      the role of Nos1(PVH) neurons in energy balance, we used Cre-dependent viral
      vectors to both map their efferent projections and test their functional output
      in mice. Here we show that Nos1(PVH) neurons project to hindbrain and spinal cord
      regions important for food intake and energy expenditure control. Moreover,
      pharmacogenetic activation of Nos1(PVH) neurons suppresses feeding to a similar
      extent as Sim1(PVH) neurons, and increases energy expenditure and activity.
      Furthermore, we found that oxytocin-expressing PVH neurons (OXT(PVH)) are a
      subset of Nos1(PVH) neurons. OXT(PVH) cells project to preganglionic, sympathetic
      neurons in the thoracic spinal cord and increase energy expenditure upon
      activation, though not to the same extent as Nos1(PVH) neurons; their activation
      fails to alter feeding, however. Thus, Nos1(PVH) neurons promote negative energy
      balance through changes in feeding and energy expenditure, whereas OXT(PVH)
      neurons regulate energy expenditure alone, suggesting a crucial role for non-OXT
      Nos1(PVH) neurons in feeding regulation. 

PMID- 25392499
TI  - Effect of human auditory efferent feedback on cochlear gain and compression.
AB  - The mammalian auditory system includes a brainstem-mediated efferent pathway from
      the superior olivary complex by way of the medial olivocochlear system, which
      reduces the cochlear response to sound (Warr and Guinan, 1979; Liberman et al.,
      1996). The human medial olivocochlear response has an onset delay of between 25
      and 40 ms and rise and decay constants in the region of 280 and 160 ms,
      respectively (Backus and Guinan, 2006). Physiological studies with nonhuman
      mammals indicate that onset and decay characteristics of efferent activation are
      dependent on the temporal and level characteristics of the auditory stimulus
      (Bacon and Smith, 1991; Guinan and Stankovic, 1996). This study uses a novel
      psychoacoustical masking technique using a precursor sound to obtain a measure of
      the efferent effect in humans. This technique avoids confounds currently
      associated with other psychoacoustical measures. Both temporal and level
      dependency of the efferent effect was measured, providing a comprehensive measure
      of the effect of human auditory efferents on cochlear gain and compression.
      Results indicate that a precursor (>20 dB SPL) induced efferent activation,
      resulting in a decrease in both maximum gain and maximum compression, with
      linearization of the compressive function for input sound levels between 50 and
      70 dB SPL. Estimated gain decreased as precursor level increased, and increased
      as the silent interval between the precursor and combined masker-signal stimulus
      increased, consistent with a decay of the efferent effect. Human auditory
      efferent activation linearizes the cochlear response for mid-level sounds while
      reducing maximum gain. 

PMID- 25392500
TI  - Regulation of neuronal gene expression and survival by basal NMDA receptor
      activity: a role for histone deacetylase 4.
AB  - Neuronal gene expression is modulated by activity via calcium-permeable receptors
      such as NMDA receptors (NMDARs). While gene expression changes downstream of
      evoked NMDAR activity have been well studied, much less is known about gene
      expression changes that occur under conditions of basal neuronal activity. In
      mouse dissociated hippocampal neuronal cultures, we found that a broad NMDAR
      antagonist, AP5, induced robust gene expression changes under basal activity, but
      subtype-specific antagonists did not. While some of the gene expression changes
      are also known to be downstream of stimulated NMDAR activity, others appear
      specific to basal NMDAR activity. The genes altered by AP5 treatment of basal
      cultures were enriched for pathways related to class IIa histone deacetylases
      (HDACs), apoptosis, and synapse-related signaling. Specifically, AP5 altered the
      expression of all three class IIa HDACs that are highly expressed in the brain,
      HDAC4, HDAC5, and HDAC9, and also induced nuclear accumulation of HDAC4. HDAC4
      knockdown abolished a subset of the gene expression changes induced by AP5, and
      led to neuronal death under long-term tetrodotoxin or AP5 treatment in rat
      hippocampal organotypic slice cultures. These data suggest that basal, but not
      evoked, NMDAR activity regulates gene expression in part through HDAC4, and, that
      HDAC4 has neuroprotective functions under conditions of low NMDAR activity. 

PMID- 25392502
TI  - Mammalian target of rapamycin's distinct roles and effectiveness in promoting
      compensatory axonal sprouting in the injured CNS.
AB  - Mammalian target of rapamycin (mTOR) functions as a master sensor of nutrients
      and energy, and controls protein translation and cell growth. Deletion of
      phosphatase and tensin homolog (PTEN) in adult CNS neurons promotes regeneration
      of injured axons in an mTOR-dependent manner. However, others have demonstrated
      mTOR-independent axon regeneration in different cell types, raising the question
      of how broadly mTOR regulates axonal regrowth across different systems. Here we
      define the role of mTOR in promoting collateral sprouting of spared axons, a key
      axonal remodeling mechanism by which functions are recovered after CNS injury.
      Using pharmacological inhibition, we demonstrate that mTOR is dispensable for the
      robust spontaneous sprouting of corticospinal tract axons seen after pyramidotomy
      in postnatal mice. In contrast, moderate spontaneous axonal sprouting and induced
      sprouting seen under different conditions in young adult mice (i.e., PTEN
      deletion or degradation of chondroitin proteoglycans; CSPGs) are both reduced
      upon mTOR inhibition. In addition, to further determine the potency of mTOR in
      promoting sprouting responses, we coinactivate PTEN and CSPGs, and demonstrate
      that this combination leads to an additive increase in axonal sprouting compared
      with single treatments. Our findings reveal a developmental switch in mTOR
      dependency for inducing axonal sprouting, and indicate that PTEN deletion in
      adult neurons neither recapitulates the regrowth program of postnatal animals,
      nor is sufficient to completely overcome an inhibitory environment. Accordingly,
      exploiting mTOR levels by targeting PTEN combined with CSPG degradation
      represents a promising strategy to promote extensive axonal plasticity in adult
      mammals. 

PMID- 25392501
TI  - Advances in understanding mechanisms of thalamic relays in cognition and
      behavior.
AB  - The main impetus for a mini-symposium on corticothalamic interrelationships was
      the recent number of studies highlighting the role of the thalamus in aspects of
      cognition beyond sensory processing. The thalamus contributes to a range of basic
      cognitive behaviors that include learning and memory, inhibitory control,
      decision-making, and the control of visual orienting responses. Its functions are
      deeply intertwined with those of the better studied cortex, although the
      principles governing its coordination with the cortex remain opaque, particularly
      in higher-level aspects of cognition. How should the thalamus be viewed in the
      context of the rest of the brain? Although its role extends well beyond relaying
      of sensory information from the periphery, the main function of many of its
      subdivisions does appear to be that of a relay station, transmitting neural
      signals primarily to the cerebral cortex from a number of brain areas. In
      cognition, its main contribution may thus be to coordinate signals between
      diverse regions of the telencephalon, including the neocortex, hippocampus,
      amygdala, and striatum. This central coordination is further subject to
      considerable extrinsic control, for example, inhibition from the basal ganglia,
      zona incerta, and pretectal regions, and chemical modulation from ascending
      neurotransmitter systems. What follows is a brief review on the role of the
      thalamus in aspects of cognition and behavior, focusing on a summary of the
      topics covered in a mini-symposium held at the Society for Neuroscience meeting,
      2014. 

PMID- 25392503
TI  - The transcription factor GTF2IRD1 regulates the topology and function of
      photoreceptors by modulating photoreceptor gene expression across the retina.
AB  - The mechanisms that specify photoreceptor cell-fate determination, especially as
      regards to short-wave-sensitive (S) versus medium-wave-sensitive (M) cone
      identity, and maintain their nature and function, are not fully understood. Here
      we report the importance of general transcription factor II-I repeat domain
      containing protein 1 (GTF2IRD1) in maintaining M cone cell identity and function
      as well as rod function. In the mouse, GTF2IRD1 is expressed in cell-fate
      determined photoreceptors at postnatal day 10. GTF2IRD1 binds to enhancer and
      promoter regions in the mouse rhodopsin, M- and S-opsin genes, but regulates
      their expression differentially. Through interaction with the transcription
      factors CRX and thyroid hormone receptor beta 2, it enhances M-opsin expression,
      whereas it suppresses S-opsin expression; and with CRX and NRL, it enhances
      rhodopsin expression. In an apparent paradox, although GTF2IRD1 is widely
      expressed in multiple cell types across the retina, knock-out of GTF2IRD1 alters
      the retinal expression of only a limited number of annotated genes.
      Interestingly, however, the null mutation leads to altered topology of cone opsin
      expression in the retina, with aberrant S-opsin overexpression and M-opsin
      underexpression in M cones. Gtf2ird1-null mice also demonstrate abnormal M cone
      and rod electrophysiological responses. These findings suggest an important role
      for GTF2IRD1 in regulating the level and topology of rod and cone gene
      expression, and in maintaining normal retinal function. 

PMID- 25392505
TI  - Olfactory aversive conditioning during sleep reduces cigarette-smoking behavior.
AB  - Recent findings suggest that novel associations can be learned during sleep.
      However, whether associative learning during sleep can alter later waking
      behavior and whether such behavioral changes last for minutes, hours, or days
      remain unknown. We tested the hypothesis that olfactory aversive conditioning
      during sleep will alter cigarette-smoking behavior during ensuing wakefulness. A
      total of 66 human subjects wishing to quit smoking participated in the study (23
      females; mean age, 28.7 +/- 5.2 years). Subjects completed a daily smoking diary
      detailing the number of cigarettes smoked during 7 d before and following a 1 d
      or night protocol of conditioning between cigarette odor and profoundly
      unpleasant odors. We observed significant reductions in the number of cigarettes
      smoked following olfactory aversive conditioning during stage 2 and rapid eye
      movement (REM) sleep but not following aversive conditioning during wakefulness
      (p < 0.05). Moreover, the reduction in smoking following aversive conditioning
      during stage 2 (34.4 +/- 30.1%) was greater and longer lasting compared with the
      reduction following aversive conditioning during REM (11.9 +/- 19.2%, p < 0.05).
      Finally, the reduction in smoking following aversive conditioning during sleep
      was significantly greater than in two separate control sleep experiments that
      tested aversive odors alone and the effects of cigarette odors and aversive odors
      without pairing. To conclude, a single night of olfactory aversive conditioning
      during sleep significantly reduced cigarette-smoking behavior in a sleep stage
      dependent manner, and this effect persisted for several days. 

PMID- 25392504
TI  - Short-term increases in transient receptor potential vanilloid-1 mediate stress
      induced enhancement of neuronal excitation.
AB  - Progression of neurodegeneration in disease and injury is influenced by the
      response of individual neurons to stressful stimuli and whether this response
      includes mechanisms to counter declining function. Transient receptor potential
      (TRP) cation channels transduce a variety of disease-relevant stimuli and can
      mediate diverse stress-dependent changes in physiology, both presynaptic and
      postsynaptic. Recently, we demonstrated that knock-out or pharmacological
      inhibition of the TRP vanilloid-1 (TRPV1) capsaicin-sensitive subunit accelerates
      degeneration of retinal ganglion cell neurons and their axons with elevated
      ocular pressure, the critical stressor in the most common optic neuropathy,
      glaucoma. Here we probed the mechanism of the influence of TRPV1 on ganglion cell
      survival in mouse models of glaucoma. We found that induced elevations of ocular
      pressure increased TRPV1 in ganglion cells and its colocalization at excitatory
      synapses to their dendrites, whereas chronic elevation progressively increased
      ganglion cell Trpv1 mRNA. Enhanced TRPV1 expression in ganglion cells was
      transient and supported a reversal of the effect of TRPV1 on ganglion cells from
      hyperpolarizing to depolarizing, which was also transient. Short-term enhancement
      of TRPV1-mediated activity led to a delayed increase in axonal spontaneous
      excitation that was absent in ganglion cells from Trpv1(-/-) retina. In isolated
      ganglion cells, pharmacologically activated TRPV1 mobilized to discrete nodes
      along ganglion cell dendrites that corresponded to sites of elevated Ca(2+).
      These results suggest that TRPV1 may promote retinal ganglion cell survival
      through transient enhancement of local excitation and axonal activity in response
      to ocular stress. 

PMID- 25392506
TI  - Visualizing the engram: learning stabilizes odor representations in the olfactory
      network.
AB  - The nature of memory is a central issue in neuroscience. How does our
      representation of the world change with learning and experience? Here we use the
      transcription of Arc mRNA, which permits probing the neural representations of
      temporally separated events, to address this in a well characterized odor
      learning model. Rat pups readily associate odor with maternal care. In pups, the
      lateralized olfactory networks are independent, permitting separate training and
      within-subject control. We use multiday training to create an enduring memory of
      peppermint odor. Training stabilized rewarded, but not nonrewarded, odor
      representations in both mitral cells and associated granule cells of the
      olfactory bulb and in the pyramidal cells of the anterior piriform cortex. An
      enlarged core of stable, likely highly active neurons represent rewarded odor at
      both stages of the olfactory network. Odor representations in anterior piriform
      cortex were sparser than typical in adult rat and did not enlarge with learning.
      This sparser representation of odor is congruent with the maturation of lateral
      olfactory tract input in rat pups. Cortical representations elsewhere have been
      shown to be highly variable in electrophysiological experiments, suggesting
      brains operate normally using dynamic and network-modulated representations. The
      olfactory cortical representations here are consistent with the generalized
      associative model of sparse variable cortical representation, as normal responses
      to repeated odors were highly variable (~70% of the cells change as indexed by
      Arc). Learning and memory modified rewarded odor ensembles to increase stability
      in a core representational component. 

PMID- 25392507
TI  - Anatomical connections of the visual word form area.
AB  - The visual word form area (VWFA), a region systematically involved in the
      identification of written words, occupies a reproducible location in the left
      occipitotemporal sulcus in expert readers of all cultures. Such a reproducible
      localization is paradoxical, given that reading is a recent invention that could
      not have influenced the genetic evolution of the cortex. Here, we test the
      hypothesis that the VWFA recycles a region of the ventral visual cortex that
      shows a high degree of anatomical connectivity to perisylvian language areas,
      thus providing an efficient circuit for both grapheme-phoneme conversion and
      lexical access. In two distinct experiments, using high-resolution diffusion
      weighted data from 75 human subjects, we show that (1) the VWFA, compared with
      the fusiform face area, shows higher connectivity to left-hemispheric perisylvian
      superior temporal, anterior temporal and inferior frontal areas; (2) on a
      posterior-to-anterior axis, its localization within the left occipitotemporal
      sulcus maps onto a peak of connectivity with language areas, with slightly
      distinct subregions showing preferential projections to areas respectively
      involved in grapheme-phoneme conversion and lexical access. In agreement with
      functional data on the VWFA in blind subjects, the results suggest that
      connectivity to language areas, over and above visual factors, may be the primary
      determinant of VWFA localization. 

PMID- 25392508
TI  - PICK1 mediates synaptic recruitment of AMPA receptors at neurexin-induced
      postsynaptic sites.
AB  - In the CNS, synapse formation and maturation play crucial roles in the
      construction and consolidation of neuronal circuits. Neurexin and neuroligin
      localize on the opposite sides of synaptic membrane and interact with each other
      to promote the assembly and specialization of synapses. However, the excitatory
      synapses induced by the neurexin-neuroligin complex are initially immature
      synapses that lack AMPA receptors. Previously, PICK1 (protein interacting with C
      kinase 1) was shown to cluster and regulate the synaptic localization of AMPA
      receptors. Here, we report that during synaptogenesis induced by neurexin in
      cultured neurons from rat hippocampus, PICK1 recruited AMPA receptors to immature
      postsynaptic sites. This synaptic recruitment of AMPA receptors depended on the
      interaction between GluA2 and PICK1, and on the lipid-binding ability of PICK1,
      but not the interaction between PICK1 and neuroligin. Last, our results
      demonstrated that the recruitment of GluA2 to synapses could be prevented by
      ICA69 (islet cell autoantigen 69 kDa), a key binding partner of PICK1. Our study
      showed that PICK1, being negatively regulated by ICA69, could facilitate synapse
      maturation. 

PMID- 25392509
TI  - Accelerated changes in white matter microstructure during aging: a longitudinal
      diffusion tensor imaging study.
AB  - It is well established that human brain white matter structure changes with
      aging, but the timescale and spatial distribution of this change remain
      uncertain. Cross-sectional diffusion tensor imaging (DTI) studies indicate that,
      after a period of relative stability during adulthood, there is an accelerated
      decline in anisotropy and increase in diffusivity values during senescence; and,
      spatially, results have been discussed within the context of several anatomical
      frameworks. However, inferring trajectories of change from cross-sectional data
      can be challenging; and, as yet, there have been no longitudinal reports of the
      timescale and spatial distribution of age-related white matter change in healthy
      adults across the adult lifespan. In a longitudinal DTI study of 203 adults
      between 20 and 84 years of age, we used tract-based spatial statistics to
      characterize the pattern of annual change in fractional anisotropy, axial
      diffusivity, radial diffusivity, and mean diffusivity and examined whether there
      was an acceleration of change with age. We found extensive and overlapping
      significant annual decreases in fractional anisotropy, and increases in axial
      diffusivity, radial diffusivity, and mean diffusivity. Spatially, results were
      consistent with inferior-to-superior gradients of lesser-to-greater
      vulnerability. Annual change increased with age, particularly within superior
      regions, with age-related decline estimated to begin in the fifth decade.
      Charting white matter microstructural changes in healthy aging provides essential
      context to clinical studies, and future studies should compare age trajectories
      between healthy participants and at-risk populations and also explore the
      relationship between DTI rates of change and cognitive decline. 

PMID- 25392511
TI  - Differentiating intended sensory outcome from underlying motor actions in the
      human brain.
AB  - To achieve a certain sensory outcome, multiple actions can be executed. For
      example, unlocking a door might require clockwise or counterclockwise key turns
      depending on regional norms. Using fMRI in healthy human subjects, we examined
      the neural networks that dissociate intended sensory outcome from underlying
      motor actions. Subjects controlled a figure on a computer screen by performing
      pen traces on an MR-compatible digital tablet. Our design allowed us to
      dissociate intended sensory outcome (moving the figure in a certain direction)
      from the underlying motor action (horizontal/vertical pen traces). Using
      multivoxel pattern analysis and a whole-brain searchlight strategy, we found that
      activity patterns in left (contralateral) motor and parietal cortex and also
      right (ipsilateral) motor cortex significantly discriminated direction of pen
      traces regardless of intended direction of figure movement. Conversely, activity
      patterns in right superior parietal lobule and premotor cortex, and also left
      frontopolar cortex, significantly discriminated intended direction of figure
      movement regardless of underlying direction of hand movement. Together, these
      results highlight the role of ipsilateral motor cortex in coding movement
      directions and point to a network of brain regions involved in high order
      representation of intended sensory outcome that is dissociated from specific
      motor plans. 

PMID- 25392510
TI  - Auditory cortex is required for fear potentiation of gap detection.
AB  - Auditory cortex is necessary for the perceptual detection of brief gaps in noise,
      but is not necessary for many other auditory tasks such as frequency
      discrimination, prepulse inhibition of startle responses, or fear conditioning
      with pure tones. It remains unclear why auditory cortex should be necessary for
      some auditory tasks but not others. One possibility is that auditory cortex is
      causally involved in gap detection and other forms of temporal processing in
      order to associate meaning with temporally structured sounds. This predicts that
      auditory cortex should be necessary for associating meaning with gaps. To test
      this prediction, we developed a fear conditioning paradigm for mice based on gap
      detection. We found that pairing a 10 or 100 ms gap with an aversive stimulus
      caused a robust enhancement of gap detection measured 6 h later, which we refer
      to as fear potentiation of gap detection. Optogenetic suppression of auditory
      cortex during pairing abolished this fear potentiation, indicating that auditory
      cortex is critically involved in associating temporally structured sounds with
      emotionally salient events. 

PMID- 25392512
TI  - Target-specific properties of thalamocortical synapses onto layer 4 of mouse
      primary visual cortex.
AB  - In primary sensory cortices, thalamocortical (TC) inputs can directly activate
      excitatory and inhibitory neurons. In vivo experiments in the main input layer
      (L4) of primary visual cortex (V1) have shown that excitatory and inhibitory
      neurons have different tuning properties. The different functional properties may
      arise from distinct intrinsic properties of L4 neurons, but could also depend on
      cell type-specific properties of the synaptic inputs from the lateral geniculate
      nucleus of the thalamus (LGN) onto L4 neurons. While anatomical studies
      identified LGN inputs onto both excitatory and inhibitory neurons in V1, their
      synaptic properties have not been investigated. Here we used an optogenetic
      approach to selectively activate LGN terminal fields in acute coronal slices
      containing V1, and recorded monosynaptic currents from excitatory and inhibitory
      neurons in L4. LGN afferents made monosynaptic connections with pyramidal (Pyr)
      and fast-spiking (FS) neurons. TC EPSCs on FS neurons were larger and showed
      steeper short-term depression in response to repetitive stimulation than those on
      Pyr neurons. LGN inputs onto Pyr and FS neurons also differed in postsynaptic
      receptor composition and organization of presynaptic release sites. Together, our
      results demonstrate that LGN input onto L4 neurons in mouse V1 have target
      specific presynaptic and postsynaptic properties. Distinct mechanisms of
      activation of feedforward excitatory and inhibitory neurons in the main input
      layer of V1 are likely to endow neurons with different response properties to
      incoming visual stimuli. 

PMID- 25392513
TI  - White matter microstructure in transsexuals and controls investigated by
      diffusion tensor imaging.
AB  - Biological causes underpinning the well known gender dimorphisms in human
      behavior, cognition, and emotion have received increased attention in recent
      years. The advent of diffusion-weighted magnetic resonance imaging has permitted
      the investigation of the white matter microstructure in unprecedented detail.
      Here, we aimed to study the potential influences of biological sex, gender
      identity, sex hormones, and sexual orientation on white matter microstructure by
      investigating transsexuals and healthy controls using diffusion tensor imaging
      (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF)
      transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI
      at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were
      calculated using tract-based spatial statistics (TBSS) and fiber tractography.
      Results showed widespread significant differences in mean diffusivity between
      groups in almost all white matter tracts. FCs had highest mean diffusivities,
      followed by FtM transsexuals with lower values, MtF transsexuals with further
      reduced values, and MCs with lowest values. Investigating axial and radial
      diffusivities showed that a transition in axial diffusivity accounted for mean
      diffusivity results. No significant differences in fractional anisotropy maps
      were found between groups. Plasma testosterone levels were strongly correlated
      with mean, axial, and radial diffusivities. However, controlling for individual
      estradiol, testosterone, or progesterone plasma levels or for subjects' sexual
      orientation did not change group differences. Our data harmonize with the
      hypothesis that fiber tract development is influenced by the hormonal environment
      during late prenatal and early postnatal brain development. 

PMID- 25392514
TI  - Voluntary physical exercise promotes ocular dominance plasticity in adult mouse
      primary visual cortex.
AB  - Ocular dominance (OD) plasticity in the mouse primary visual cortex (V1) declines
      during aging and is absent beyond postnatal day (P) 110 when mice are raised in
      standard cages (SCs; Lehmann and Lowel, 2008). In contrast, raising mice in an
      enriched environment (EE) preserved a juvenile-like OD plasticity into late
      adulthood (Greifzu et al., 2014). EE raising provides the mice with more social
      interactions, voluntary physical exercise, and cognitive stimulation compared
      with SC, raising the question whether all components are needed or whether one of
      them is already sufficient to prolong plasticity. To test whether voluntary
      physical exercise alone already prolongs the sensitive phase for OD plasticity,
      we raised mice from 7 d before birth to adulthood in slightly larger than normal
      SCs with or without a running wheel (RW). When the mice were older than P135, we
      visualized V1 activity before and after monocular deprivation (MD) using
      intrinsic signal optical imaging. Adult RW-raised mice continued to show an OD
      shift toward the open eye after 7 d of MD, while age-matched SC mice without a RW
      did not show OD plasticity. Notably, running just during the 7 d MD period
      restored OD plasticity in adult SC-raised mice. In addition, the OD shift of the
      RW mice was mediated by a decrease of deprived-eye responses in V1, a signature
      of "juvenile-like" plasticity. We conclude that voluntary physical exercise alone
      is sufficient to promote plasticity in adult mouse V1. 

PMID- 25392515
TI  - Emerging roles of extracellular vesicles in the nervous system.
AB  - Information exchange executed by extracellular vesicles, including exosomes, is a
      newly described form of intercellular communication important in the development
      and physiology of neural systems. These vesicles can be released from cells, are
      packed with information including signaling proteins and both coding and
      regulatory RNAs, and can be taken up by target cells, thereby facilitating the
      transfer of multilevel information. Recent studies demonstrate their critical
      role in physiological processes, including nerve regeneration, synaptic function,
      and behavior. These vesicles also have a sinister role in the propagation of
      toxic amyloid proteins in neurodegenerative conditions, including prion diseases
      and Alzheimer's and Parkinson's diseases, in inducing neuroinflammation by
      exchange of information between the neurons and glia, as well as in aiding tumor
      progression in the brain by subversion of normal cells. This article provides a
      summary of topics covered in a symposium and is not meant to be a comprehensive
      review of the subject. 

PMID- 25392516
TI  - Gut microbes and the brain: paradigm shift in neuroscience.
AB  - The discovery of the size and complexity of the human microbiome has resulted in
      an ongoing reevaluation of many concepts of health and disease, including
      diseases affecting the CNS. A growing body of preclinical literature has
      demonstrated bidirectional signaling between the brain and the gut microbiome,
      involving multiple neurocrine and endocrine signaling mechanisms. While
      psychological and physical stressors can affect the composition and metabolic
      activity of the gut microbiota, experimental changes to the gut microbiome can
      affect emotional behavior and related brain systems. These findings have resulted
      in speculation that alterations in the gut microbiome may play a
      pathophysiological role in human brain diseases, including autism spectrum
      disorder, anxiety, depression, and chronic pain. Ongoing large-scale population
      based studies of the gut microbiome and brain imaging studies looking at the
      effect of gut microbiome modulation on brain responses to emotion-related stimuli
      are seeking to validate these speculations. This article is a summary of emerging
      topics covered in a symposium and is not meant to be a comprehensive review of
      the subject. 

PMID- 25392517
TI  - Attention, reward, and information seeking.
AB  - Decision making is thought to be guided by the values of alternative options and
      involve the accumulation of evidence to an internal bound. However, in natural
      behavior, evidence accumulation is an active process whereby subjects decide when
      and which sensory stimulus to sample. These sampling decisions are naturally
      served by attention and rapid eye movements (saccades), but little is known about
      how saccades are controlled to guide future actions. Here we review evidence that
      was discussed at a recent symposium, which suggests that information selection
      involves basal ganglia and cortical mechanisms and that, across different
      contexts, it is guided by two central factors: the gains in reward and gains in
      information (uncertainty reduction) associated with sensory cues. 

PMID- 25392518
TI  - Preventing the onset of psychosis: not quite there yet.

PMID- 25392519
TI  - Polygenic risk for schizophrenia associated with working memory-related
      prefrontal brain activation in patients with schizophrenia and healthy controls.
AB  - Schizophrenia is a highly heritable and polygenic disease, and identified common
      genetic variants have shown weak individual effects. Many studies have reported
      altered working memory (WM)-related brain activation in schizophrenia,
      preferentially in the frontal lobe. Such differences in brain activations could
      reflect inherited alterations possibly involved in the disease etiology, or
      rather secondary disease-related mechanisms. The use of polygenic risk scores
      (PGRS) based on a large number of risk polymorphisms with small effects is a
      valuable approach to examine the effect of cumulative genetic risk on brain
      functioning. This study examined the impact of cumulative genetic risk for
      schizophrenia on WM-related brain activations, assessed with functional magnetic
      resonance imaging. For each participant (63 schizophrenia patients and 118
      healthy controls), we calculated a PGRS for schizophrenia based on 18 862 single
      nucleotide polymorphism in a large multicenter genome-wide association study
      including 9146 schizophrenia patients and 12 111 controls, performed by the
      Psychiatric Genomics Consortium. As expected, the PGRS was significantly higher
      in patients compared with healthy controls. Further, the PGRS was related to
      differences in frontal lobe brain activation between high and low WM demand.
      Specifically, even in absence of main effects of diagnosis, increased PGRS was
      associated with decreased activation difference in the right middle-superior
      prefrontal cortex (BA 10/11) and the right inferior frontal gyrus (BA 45). This
      effect was seen in both cases and controls, and was not influenced by sex, age,
      or task performance. The findings support the notion of dysregulation of frontal
      lobe functioning as an inherited vulnerability factor in schizophrenia. 

PMID- 25392521
TI  - Validation of a Simple Screening Tool for Identifying Unmet Palliative Care Needs
      in Patients With Cancer.
AB  - PURPOSE: The National Comprehensive Cancer Network (NCCN) palliative care (PC)
      guideline recommends PC screening for all patients and provides criteria for
      identifying those in need of referral to a PC specialist. This two-step process
      has not yet been validated as accurately identifying patients in need. The aim of
      this study was to validate a simplified method for screening and referral based
      on the existing guideline criteria. METHODS: An 11-item screening tool was
      created, with scores from 0 to 14. Content validity was assessed by a panel of
      local PC experts. Construct and criterion validities were evaluated using data
      obtained from a previous study of guideline-based screening and referral.
      RESULTS: Content validity of the tool was high, with eight items rated as
      essential. Patients who were closer to death had significantly higher scores,
      indicating its construct validity. Scores were also higher in patients who were
      identified as needing a consult and in those who had worse pain and other
      symptoms, indicating its criterion validity. Using a score of >= 5 as the
      trigger, approximately one third of hospitalized patients in the previous study
      would have been referred to a PC specialist, twice as many as occurred when the
      attending oncologist relied on his or her clinical judgment. CONCLUSION: The tool
      seems to be a valid method for identifying patients with cancer with complex PC
      needs who would benefit from a PC consult. Reliability testing, external
      validation, and demonstration of the utility of the tool as a decision aid all
      await confirmation.

PMID- 25392520
TI  - Evidence from structural and diffusion tensor imaging for frontotemporal deficits
      in psychometric schizotypy.
AB  - BACKGROUND: Previous studies of nonclinical samples exhibiting schizotypal traits
      have provided support for the existence of a continuous distribution of psychotic
      symptoms in the general population. Few studies, however, have examined the
      neural correlates of psychometric schizotypy using structural and diffusion
      tensor imaging (DTI). METHODS: Healthy volunteers between the ages of 18 and 68
      were recruited from the community and assessed using the Schizotypal Personality
      Questionnaire and received structural and DTI exams. Participants with high (N =
      67) and low (N = 71) psychometric schizotypy were compared on gray and white
      matter volume, and cortical thickness in frontal and temporal lobe regions and on
      fractional anisotropy (FA) within 5 association tracts traversing the frontal and
      temporal lobes. RESULTS: Higher levels of schizotypy were associated with lower
      overall volumes of gray matter in both the frontal and temporal lobes and lower
      gray matter thickness in the temporal lobe. Regionally specific effects were
      evident in both white matter and gray matter volume of the rostral middle frontal
      cortex and gray matter volume in the pars orbitalis. Moreover, relative to
      individuals who scored low, those who scored high in schizotypy had lower FA in
      the inferior fronto-occipital fasciculus as well as greater asymmetry (right >
      left) in the uncinate fasciculus. CONCLUSIONS: These findings are broadly
      consistent with recent data on the neurobiological correlates of psychometric
      schizotypy as well as findings in schizotypal personality disorder and
      schizophrenia and suggest that frontotemporal lobe dysfunction may represent a
      core component of the psychosis phenotype.

PMID- 25392522
TI  - Are Physicians Choosing Wisely When Imaging for Distant Metastases in Women With
      Operable Breast Cancer?
AB  - PURPOSE: In 2012, the American Society of Clinical Oncology (ASCO) published its
      inaugural Top Five recommendations for "choosing wisely" in oncology. One
      recommendation was to avoid imaging for metastatic disease in asymptomatic
      patients with early-stage breast cancer. We assessed whether local practice is in
      keeping with provincial practice guidelines and whether publication of the ASCO
      recommendations had any significant impact on this. METHODS: A retrospective
      review of staging imaging for distant metastases was performed in patients with
      primary operable (early-stage) breast cancer seen at a large Canadian academic
      cancer center. RESULTS: A total of 200 patient medical records were reviewed: 100
      patients from 2011 (pre-ASCO Top Five), and 100 after September 2012 (post-ASCO
      Top Five). Baseline patient and tumor characteristics were similar in both
      groups. Overall, 169 patients (84.5%) underwent at least one imaging test (mean,
      3.6 tests per imaged patient); 154 patients (77.0%) underwent imaging that was
      not in keeping with the spirit of the local guideline recommendations. The
      frequency of imaging did not change after publication of the ASCO
      recommendations. Furthermore, imaging to clarify indeterminate initial imaging
      was required in 51 (30.2%) of 169 patients. None of the confirmatory imaging
      results ultimately revealed metastatic disease. CONCLUSION: Despite the presence
      of local imaging guidelines, patients with early-stage breast cancer still
      undergo imaging for distant metastases. There was no reduction in imaging after
      publication of the ASCO Top Five recommendations. Broader knowledge translation
      strategies beyond publication are needed if recommendations are to be implemented
      into routine clinical practice.

PMID- 25392523
TI  - Estimating the State-Level Supply of Cancer Care Providers: Preparing to Meet
      Workforce Needs in the Wake of Health Care Reform.
AB  - PURPOSE: This study describes the supply of cancer care providers-physicians,
      nurse practitioners (NPs), and physician assistants (PAs)-in Nebraska and
      analyzes changes in the supply over a 5-year period. METHOD: We used workforce
      survey data for the years 2008 to 2012 from the Health Professions Tracking
      Service to analyze the cancer care workforce supply in the state of Nebraska. The
      supply of cancer care providers was analyzed over the 5-year period on the basis
      of age, sex, specialty, and practice location; distribution of work hours for
      cancer care physicians was analyzed for 2012. RESULTS: From 2008 to 2012, there
      was a 3.3% increase in the number of cancer care physicians. Majority of the
      cancer care physicians (82.5%), NPs (81.1%), and PAs (80%) reported working in
      urban counties, whereas approximately half of the state's population resides in
      rural counties (47%). Compared with the national distribution, Nebraska has a
      lower proportion of medical oncologists, radiation oncologists, and pediatric
      hematologists/oncologists. The gap between the number of cancer care physicians
      age >= 64 years and the number younger than 40 years is slowly closing in
      Nebraska, with an increase in those age >= 64 years. CONCLUSION: Increasing
      cancer incidence and improved access to cancer care through the Affordable Care
      Act could increase demand for cancer care workers. Policymakers and legislators
      should consider a range of policies based on the best available data on the
      supply of cancer care providers and the demand for cancer care.

PMID- 25392524
TI  - Viral MHC class I-like molecule allows evasion of NK cell effector responses in
      vivo.
AB  - The outcome of mouse CMV (MCMV) infection varies among different inbred mouse
      strains depending on NK cell effector functions governed through recognition
      receptor triggering. NK cells from different mouse strains possess diverse
      repertoires of activating or inhibitory Ly49 receptors, which share some of their
      polymorphic MHC class I (MHC-I) ligands. By examining the NK cell response to
      MCMV infection in novel BALB substrains congenic for different MHC (or H-2 in
      mice) haplotypes, we show that recognition of viral MHC-I-like protein m157 by
      inhibitory Ly49C receptor allows escape from NK cell control of viral
      replication. Dominant inhibition by Ly49C bound to self-H-2(b) encoded MHC-I
      molecules masks this effect, which only becomes apparent in distinct H-2
      haplotypes, such as H-2(f). The recognition of m157-expressing cells by Ly49C
      resulted in both decreased NK cell killing in vitro and reduced rejection in
      vivo. Further, control of infection with m157-deletant (Deltam157) MCMV was
      improved in mice carrying H-2 molecules unrecognized by Ly49C but allowing
      expansion of NK cell effectors expressing activating Ly49L receptors. Hence, our
      study is the first, to our knowledge, to demonstrate that MHC-I mimicry
      strategies used by MCMV to avoid NK cell control are biologically relevant during
      in vivo viral infection. Of value for human studies is that only a few genetic
      assortments conditional on the repertoires of viral MHC-I-like proteins/host NK
      receptors/MHC haplotypes should allow efficient protection against CMV infection.

PMID- 25392525
TI  - CD4+ T cell epitopes of FliC conserved between strains of Burkholderia:
      implications for vaccines against melioidosis and cepacia complex in cystic
      fibrosis.
AB  - Burkholderia pseudomallei is the causative agent of melioidosis characterized by
      pneumonia and fatal septicemia and prevalent in Southeast Asia. Related
      Burkholderia species are strong risk factors of mortality in cystic fibrosis
      (CF). The B. pseudomallei flagellar protein FliC is strongly seroreactive and
      vaccination protects challenged mice. We assessed B. pseudomallei FliC peptide
      binding affinity to multiple HLA class II alleles and then assessed CD4 T cell
      immunity in HLA class II transgenic mice and in seropositive individuals in
      Thailand. T cell hybridomas were generated to investigate cross-reactivity
      between B. pseudomallei and the related Burkholderia species associated with
      Cepacia Complex CF. B. pseudomallei FliC contained several peptide sequences with
      ability to bind multiple HLA class II alleles. Several peptides were shown to
      encompass strong CD4 T cell epitopes in B. pseudomallei-exposed individuals and
      in HLA transgenic mice. In particular, the p38 epitope is robustly recognized by
      CD4 T cells of seropositive donors across diverse HLA haplotypes. T cell
      hybridomas against an immunogenic B. pseudomallei FliC epitope also cross-reacted
      with orthologous FliC sequences from Burkholderia multivorans and Burkholderia
      cenocepacia, important pathogens in CF. Epitopes within FliC were accessible for
      processing and presentation from live or heat-killed bacteria, demonstrating that
      flagellin enters the HLA class II Ag presentation pathway during infection of
      macrophages with B. cenocepacia. Collectively, the data support the possibility
      of incorporating FliC T cell epitopes into vaccination programs targeting both at
      risk individuals in B. pseudomallei endemic regions as well as CF patients. 

PMID- 25392526
TI  - Cutting edge: New chimeric NOD2/TLR2 adjuvant drastically increases vaccine
      immunogenicity.
AB  - TLR ligands are critical activators of innate immunity and are being developed as
      vaccine adjuvants. However, their usefulness in conjunction with NOD-like
      receptor agonists remains poorly studied. In this study, we evaluated a new
      ligand that targets both TLR2 and NOD2 receptors. We assessed its ability to
      enhance dendritic cell maturation in vitro in addition to improving systemic and
      mucosal immune responses in mice. The chimeric NOD2/TLR2 ligand induced
      synergistic upregulation of dendritic cell maturation markers, costimulatory
      molecules, and secretion of proinflammatory cytokines compared with combinations
      of separate ligands. Furthermore, when coadministered with biodegradable
      nanoparticles carrying a model Ag, the ligand was able to induce high Ag-specific
      IgA and IgG titers at both systemic and mucosal sites after parenteral
      immunizations. These findings point out the potential utility of chimeric
      molecules TLR/NOD as adjuvants for vaccines to induce systemic and mucosal immune
      responses. 

PMID- 25392528
TI  - PARP-1 mediates LPS-induced HMGB1 release by macrophages through regulation of
      HMGB1 acetylation.
AB  - The high-mobility group box protein 1 (HMGB1) is increasingly recognized as an
      important inflammatory mediator. In some cases, the release of HMGB1 is regulated
      by poly(ADP-ribose) polymerase-1 (PARP-1), but the mechanism is still unclear. In
      this study, we report that PARP-1 activation contributes to LPS-induced
      PARylation of HMGB1, but the PARylation of HMGB1 is insufficient to direct its
      migration from the nucleus to the cytoplasm; PARP-1 regulates the translocation
      of HMGB1 to the cytoplasm through upregulating the acetylation of HMGB1. In mouse
      bone marrow-derived macrophages, genetic and pharmacological inhibition of PARP-1
      suppressed LPS-induced translocation and release of HMGB1. Increased PARylation
      was accompanied with the nucleus-to-cytoplasm translocation and release of HMGB1
      upon LPS exposure, but PARylated HMGB1 was located at the nucleus, unlike
      acetylated HMGB1 localized at the cytoplasm in an import assay. PARP inhibitor
      and PARP-1 depletion decreased the activity ratio of histone acetyltransferases
      to histone deacetylases that elevated after LPS stimulation and impaired LPS
      induced acetylation of HMGB1. In addition, PARylation of HMGB1 facilitates its
      acetylation in an in vitro enzymatic reaction. Furthermore, reactive oxygen
      species scavenger (N-acetyl-l-cysteine) and the ERK inhibitor (FR180204) impaired
      LPS-induced PARP activation and HMGB1 release. Our findings suggest that PARP-1
      regulates LPS-induced acetylation of HMGB1 in two ways: PARylating HMGB1 to
      facilitate the latter acetylation and increasing the activity ratio of histone
      acetyltransferases to histone deacetylases. These studies revealed a new
      mechanism of PARP-1 in regulating the inflammatory response to endotoxin. 

PMID- 25392527
TI  - A novel mechanism of B cell-mediated immune suppression through CD73 expression
      and adenosine production.
AB  - Immune suppression by regulatory T cells and regulatory B cells is a critical
      mechanism to limit excess inflammation and autoimmunity. IL-10 is considered the
      major mediator of B cell-induced immune suppression. We report a novel mechanism
      for immune suppression through adenosine generation by B cells. We identified a
      novel population of B cells that expresses CD73 as well as CD39, two ectoenzymes
      that together catalyze the extracellular dephosphorylation of adenine nucleotides
      to adenosine. Whereas CD39 expression is common among B cells, CD73 expression is
      not. Approximately 30-50% of B-1 cells (B220(+)CD23(-)) and IL-10-producing B
      (B10) cells (B220(+)CD5(+)CD1d(hi)) are CD73(hi), depending on mouse strain,
      whereas few conventional B-2 cells (B220(+)CD23(+)AA4.1(-)) express CD73. In
      keeping with expression of both CD73 and CD39, we found that CD73(+) B cells
      produce adenosine in the presence of substrate, whereas B-2 cells do not. CD73(-/
      ) mice were more susceptible to dextran sulfate sodium salt (DSS)-induced colitis
      than wild type (WT) mice were, and transfer of CD73(+) B cells ameliorated the
      severity of colitis, suggesting that B cell CD73/CD39/adenosine can modulate DSS
      induced colitis. IL-10 production by B cells is not affected by CD73 deficiency.
      Interestingly, adenosine generation by IL-10(-/-) B cells is impaired because of
      reduced expression of CD73, indicating an unexpected connection between IL-10 and
      adenosine and suggesting caution in interpreting the results of studies with IL
      10(-/-) cells. Our findings demonstrate a novel regulatory role of B cells on
      colitis through adenosine generation in an IL-10-independent manner. 

PMID- 25392530
TI  - Nonenzymatic conversion of ADP-ribosylated arginines to ornithine alters the
      biological activities of human neutrophil peptide-1.
AB  - Activated neutrophils, recruited to the airway of diseased lung, release human
      neutrophil peptides (HNP1-4) that are cytotoxic to airway cells as well as
      microbes. Airway epithelial cells express arginine-specific ADP
      ribosyltransferase (ART)-1, a GPI-anchored ART that transfers ADP-ribose from NAD
      to arginines 14 and 24 of HNP-1. We previously reported that ADP-ribosyl-arginine
      is converted nonenzymatically to ornithine and that ADP-ribosylated HNP-1 and ADP
      ribosyl-HNP-(ornithine) were isolated from bronchoalveolar lavage fluid of a
      patient with idiopathic pulmonary fibrosis, indicating that these reactions occur
      in vivo. To determine effects of HNP-ornithine on the airway, three analogs of
      HNP-1, HNP-(R14orn), HNP-(R24orn), and HNP-(R14,24orn), were tested for their
      activity against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus
      aureus; their cytotoxic effects on A549, NCI-H441, small airway epithelial-like
      cells, and normal human lung fibroblasts; and their ability to stimulate IL-8 and
      TGF-beta1 release from A549 cells, and to serve as ART1 substrates. HNP and the
      three analogs had similar effects on IL-8 and TGF-beta1 release from A549 cells
      and were all cytotoxic for small airway epithelial cells, NCI-H441, and normal
      human lung fibroblasts. HNP-(R14,24orn), when compared with HNP-1 and HNP-1 with
      a single ornithine substitution for arginine 14 or 24, exhibited reduced
      cytotoxicity, but it enhanced proliferation of A549 cells and had antibacterial
      activity. Thus, arginines 14 and 24, which can be ADP ribosylated by ART1, are
      critical to the regulation of the cytotoxic and antibacterial effects of HNP-1.
      The HNP analog, HNP-(R14,24orn), lacks the epithelial cell cytotoxicity of HNP-1,
      but partially retains its antibacterial activity and thus may have clinical
      applications in airway disease. 

PMID- 25392529
TI  - The specialized proresolving mediator 17-HDHA enhances the antibody-mediated
      immune response against influenza virus: a new class of adjuvant?
AB  - Influenza viruses remain a critical global health concern. More efficacious
      vaccines are needed to protect against influenza virus, yet few adjuvants are
      approved for routine use. Specialized proresolving mediators (SPMs) are powerful
      endogenous bioactive regulators of inflammation, with great clinical
      translational properties. In this study, we investigated the ability of the SPM
      17-HDHA to enhance the adaptive immune response using an OVA immunization model
      and a preclinical influenza vaccination mouse model. Our findings revealed that
      mice immunized with OVA plus 17-HDHA or with H1N1-derived HA protein plus 17-HDHA
      increased Ag-specific Ab titers. 17-HDHA increased the number of Ab-secreting
      cells in vitro and the number of HA-specific Ab-secreting cells present in the
      bone marrow. Importantly, the 17-HDHA-mediated increased Ab production was more
      protective against live pH1N1 influenza infection in mice. To our knowledge, this
      is the first report on the biological effects of omega-3-derived SPMs on the
      humoral immune response. These findings illustrate a previously unknown
      biological link between proresolution signals and the adaptive immune system.
      Furthermore, this work has important implications for the understanding of B cell
      biology, as well as the development of new potential vaccine adjuvants. 

PMID- 25392532
TI  - Analysis of relationships between peptide/MHC structural features and naive T
      cell frequency in humans.
AB  - The structural rules governing peptide/MHC (pMHC) recognition by T cells remain
      unclear. To address this question, we performed a structural characterization of
      several HLA-A2/peptide complexes and assessed in parallel their antigenicity, by
      analyzing the frequency of the corresponding Ag-specific naive T cells in A2(+)
      and A2(-) individuals, as well as within CD4(+) and CD8(+) subsets. We were able
      to find a correlation between specific naive T cell frequency and peptide solvent
      accessibility and/or mobility for a subset of moderately prominent peptides.
      However, one single structural parameter of the pMHC complexes could not be
      identified to explain each peptide antigenicity. Enhanced pMHC antigenicity was
      associated with both highly biased TRAV usage, possibly reflecting favored
      interaction between particular pMHC complexes and germline TRAV loops, and
      peptide structural features allowing interactions with a broad range of
      permissive CDR3 loops. In this context of constrained TCR docking mode, an
      optimal peptide solvent exposed surface leading to an optimal complementarity
      with TCR interface may constitute one of the key features leading to high
      frequency of specific T cells. Altogether our results suggest that frequency of
      specific T cells depends on the fine-tuning of several parameters, the structural
      determinants governing TCR-pMHC interaction being just one of them. 

PMID- 25392531
TI  - Histone deacetylase inhibitors upregulate B cell microRNAs that silence AID and
      Blimp-1 expression for epigenetic modulation of antibody and autoantibody
      responses.
AB  - Class-switch DNA recombination (CSR) and somatic hypermutation (SHM), which
      require activation-induced cytidine deaminase (AID), and plasma cell
      differentiation, which requires B lymphocyte-induced maturation protein-1 (Blimp
      1), are critical for the generation of class-switched and hypermutated (mature)
      Ab and autoantibody responses. We show that histone deacetylase inhibitors
      valproic acid and butyrate dampened AICDA/Aicda (AID) and PRDM1/Prdm1 (Blimp-1)
      mRNAs by upregulating miR-155, miR-181b, and miR-361 to silence AICDA/Aicda, and
      miR-23b, miR-30a, and miR-125b to silence PRDM1/Prdm1, in human and mouse B
      cells. This led to downregulation of AID, Blimp-1, and X-box binding protein 1,
      thereby inhibiting CSR, SHM, and plasma cell differentiation without altering B
      cell viability or proliferation. The selectivity of histone deacetylase inhibitor
      mediated silencing of AICDA/Aicda and PRDM1/Prdm1 was emphasized by unchanged
      expression of HoxC4 and Irf4 (important inducers/modulators of AICDA/Aicda), Rev1
      and Ung (central elements for CSR/SHM), and Bcl6, Bach2, or Pax5 (repressors of
      PRDM1/Prdm1 expression), as well as unchanged expression of miR-19a/b, miR-20a,
      and miR-25, which are not known to regulate AICDA/Aicda or PRDM1/Prdm1. Through
      these B cell-intrinsic epigenetic mechanisms, valproic acid blunted class
      switched and hypermutated T-dependent and T-independent Ab responses in C57BL/6
      mice. In addition, it decreased class-switched and hypermutated autoantibodies,
      ameliorated disease, and extended survival in lupus MRL/Fas(lpr/lpr) mice. Our
      findings outline epigenetic mechanisms that modulate expression of an enzyme
      (AID) and transcription factors (Blimp-1 and X-box binding protein 1) that are
      critical to the B cell differentiation processes that underpin Ab and
      autoantibody responses. They also provide therapeutic proof-of-principle in
      autoantibody-mediated autoimmunity. 

PMID- 25392533
TI  - A signal integration model of thymic selection and natural regulatory T cell
      commitment.
AB  - The extent of TCR self-reactivity is the basis for selection of a functional and
      self-tolerant T cell repertoire and is quantified by repeated engagement of TCRs
      with a diverse pool of self-peptides complexed with self-MHC molecules. The
      strength of a TCR signal depends on the binding properties of a TCR to the
      peptide and the MHC, but it is not clear how the specificity to both components
      drives fate decisions. In this study, we propose a TCR signal-integration model
      of thymic selection that describes how thymocytes decide among distinct fates,
      not only based on a single TCR-ligand interaction, but taking into account the
      TCR stimulation history. These fates are separated based on sustained accumulated
      signals for positive selection and transient peak signals for negative selection.
      This spans up the cells into a two-dimensional space where they are either
      neglected, positively selected, negatively selected, or selected as natural
      regulatory T cells (nTregs). We show that the dynamics of the integrated signal
      can serve as a successful basis for extracting specificity of thymocytes to MHC
      and detecting the existence of cognate self-peptide-MHC. It allows to select a
      self-MHC-biased and self-peptide-tolerant T cell repertoire. Furthermore, nTregs
      in the model are enriched with MHC-specific TCRs. This allows nTregs to be more
      sensitive to activation and more cross-reactive than conventional T cells. This
      study provides a mechanistic model showing that time integration of TCR-mediated
      signals, as opposed to single-cell interaction events, is needed to gain a full
      view on the properties emerging from thymic selection. 

PMID- 25392536
TI  - Probability of eradication using vancomycin alone or in combination for
      methicillin-resistant Staphylococcus aureus bacteremia.

PMID- 25392534
TI  - Identification of antigen-specific B cell receptor sequences using public
      repertoire analysis.
AB  - High-throughput sequencing allows detailed study of the BCR repertoire
      postimmunization, but it remains unclear to what extent the de novo
      identification of Ag-specific sequences from the total BCR repertoire is
      possible. A conjugate vaccine containing Haemophilus influenzae type b (Hib) and
      group C meningococcal polysaccharides, as well as tetanus toxoid (TT), was used
      to investigate the BCR repertoire of adult humans following immunization and to
      test the hypothesis that public or convergent repertoire analysis could identify
      Ag-specific sequences. A number of Ag-specific BCR sequences have been reported
      for Hib and TT, which made a vaccine containing these two Ags an ideal
      immunological stimulus. Analysis of identical CDR3 amino acid sequences that were
      shared by individuals in the postvaccine repertoire identified a number of known
      Hib-specific sequences but only one previously described TT sequence. The
      extension of this analysis to nonidentical, but highly similar, CDR3 amino acid
      sequences revealed a number of other TT-related sequences. The anti-Hib avidity
      index postvaccination strongly correlated with the relative frequency of Hib
      specific sequences, indicating that the postvaccination public BCR repertoire may
      be related to more conventional measures of immunogenicity correlating with
      disease protection. Analysis of public BCR repertoire provided evidence of
      convergent BCR evolution in individuals exposed to the same Ags. If this finding
      is confirmed, the public repertoire could be used for rapid and direct
      identification of protective Ag-specific BCR sequences from peripheral blood. 

PMID- 25392537
TI  - Reply to "Probability of eradication using vancomycin alone or in combination for
      methicillin-resistant Staphylococcus aureus bacteremia".

PMID- 25392538
TI  - Feasibility and reproducibility of HIV-1 genotype resistance test in very-low
      level viremia.

PMID- 25392541
TI  - Intravenously injected human apolipoprotein A-I rapidly enters the central
      nervous system via the choroid plexus.
AB  - BACKGROUND: Brain lipoprotein metabolism is dependent on lipoprotein particles
      that resemble plasma high-density lipoproteins but that contain apolipoprotein
      (apo) E rather than apoA-I as their primary protein component. Astrocytes and
      microglia secrete apoE but not apoA-I; however, apoA-I is detectable in both
      cerebrospinal fluid and brain tissue lysates. The route by which plasma apoA-I
      enters the central nervous system is unknown. METHODS AND RESULTS: Steady-state
      levels of murine apoA-I in cerebrospinal fluid and interstitial fluid are 0.664
      and 0.120 MUg/mL, respectively, whereas brain tissue apoA-I is ~10% to 15% of its
      levels in liver. Recombinant, fluorescently tagged human apoA-I injected
      intravenously into mice localizes to the choroid plexus within 30 minutes and
      accumulates in a saturable, dose-dependent manner in the brain. Recombinant,
      fluorescently tagged human apoA-I accumulates in the brain for 2 hours, after
      which it is eliminated with a half-life of 10.3 hours. In vitro, human apoA-I is
      specifically bound, internalized, and transported across confluent monolayers of
      primary human choroid plexus epithelial cells and brain microvascular endothelial
      cells. CONCLUSIONS: Following intravenous injection, recombinant human apoA-I
      rapidly localizes predominantly to the choroid plexus. Because apoA-I mRNA is
      undetectable in murine brain, our results suggest that plasma apoA-I, which is
      secreted from the liver and intestine, gains access to the central nervous system
      primarily by crossing the blood-cerebrospinal fluid barrier via specific cellular
      mediated transport, although transport across the blood-brain barrier may also
      contribute to a lesser extent.

PMID- 25392543
TI  - An Oxidized Abasic Lesion as an Intramolecular Source of DNA Adducts.
AB  - 5'-(2-Phosphoryl-1,4-dioxobutane) (DOB) is a lesion produced in DNA via a variety
      of damaging agents. The DOB lesion spontaneously generates cis- and trans-but-2
      en-1,4-dial (1) via beta-elimination. Cis- and trans-but-2-en-1,4-dial forms
      exocyclic adducts with nucleosides. We used chemically synthesized DNA containing
      tritiated DOB incorporated at defined sites to examine the reactivity of cis- and
      trans-but-2-en-1,4-dial. Although the local DNA sequence does not appear to
      influence the distribution of nucleoside adducts, we find that DOB generates
      relatively high yields of cis- and trans-but-2-en-1,4-dial nucleoside adducts
      that likely are promutagenic.

PMID- 25392544
TI  - The importance of public relations and communications at the CVMA.

PMID- 25392542
TI  - Mitochondrial aldehyde dehydrogenase activation by Alda-1 inhibits
      atherosclerosis and attenuates hepatic steatosis in apolipoprotein E-knockout
      mice.
AB  - BACKGROUND: Mitochondrial dysfunction has been shown to play an important role in
      the development of atherosclerosis and nonalcoholic fatty liver disease (NAFLD).
      Mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme responsible for the
      detoxification of reactive aldehydes, is considered to exert protective function
      in mitochondria. We investigated the influence of Alda-1, an activator of ALDH2,
      on atherogenesis and on the liver steatosis in apolipoprotein E knockout (apoE(-/
      )) mice. METHODS AND RESULTS: Alda-1 caused decrease of atherosclerotic lesions
      approximately 25% as estimated by "en face" and "cross-section" methods without
      influence on plasma lipid profile, atherosclerosis-related markers of
      inflammation, and macrophage and smooth muscle content in the plaques. Plaque
      nitrotyrosine was not changed upon Alda-1 treatment, and there were no changes in
      aortic mRNA levels of factors involved in antioxidative defense, regulation of
      apoptosis, mitogenesis, and autophagy. Hematoxylin/eosin staining showed decrease
      of steatotic changes in liver of Alda-1-treated apoE(-/-) mice. Alda-1 attenuated
      formation of 4-hydroxy-2-nonenal (4-HNE) protein adducts and decreased
      triglyceride content in liver tissue. Two-dimensional electrophoresis coupled
      with mass spectrometry identified 20 differentially expressed mitochondrial
      proteins upon Alda-1 treatment in liver of apoE(-/-) mice, mostly proteins
      related to metabolism and oxidative stress. The most up-regulated were the
      proteins that participated in beta oxidation of fatty acids. CONCLUSIONS:
      Collectively, Alda-1 inhibited atherosclerosis and attenuated NAFLD in apoE(-/-)
      mice. The pattern of changes suggests a beneficial effect of Alda-1 in NAFLD;
      however, the exact liver functional consequences of the revealed alterations as
      well as the mechanism(s) of antiatherosclerotic Alda-1 action require further
      investigation.

PMID- 25392545
TI  - An ethicist's commentary on "ag-gag" laws.

PMID- 25392546
TI  - Canada: Porcine epidemic diarrhea in Canada: an emerging disease case study.

PMID- 25392547
TI  - Minimally invasive proximal interphalangeal joint arthrodesis using a locking
      compression plate and tissue engineering in horses: a pilot study.
AB  - This pilot study assessed the efficacy of 2 minimally invasive techniques for
      proximal interphalangeal (PIP) joint arthrodesis in horses. The PIP joints of
      both forelimbs (n = 6) were stabilized with locking compression plates (LCP)
      using a minimally invasive technique (LCP technique). Subsequently, for 1
      randomly selected PIP joint of each horse, surgical drilling (SurD) was performed
      and tissue engineering (TE) was applied (LCP/SurD/TE technique). Minimally
      invasive PIP joint arthrodesis with LCP demonstrated low postoperative infection
      rates. Gross and histological evaluations revealed considerable destruction of
      the articular cartilage in the LCP/SurD/TE-treated joints. In contrast, almost no
      destruction of the cartilage was observed in the LCP-treated joints. Our results
      suggest that the LCP technique alone is not sufficient for PIP joint arthrodesis
      and that the LCP/SurD/TE technique may be useful for PIP joint arthrodesis in
      horses. 

PMID- 25392548
TI  - Kinetic measurements of gait for osteoarthritis research in dogs and cats.
AB  - Over the past 2 decades the measurement of ground reaction forces (GRF) has been
      extensively used in dogs and cats to gain insights on normal locomotion,
      discrepancies under pathologic conditions, and biomechanical changes following
      surgical procedures. Ground reaction forces have become a well-established
      outcome measure of pain-related functional impairment in animals affected by
      experimental and naturally occurring osteoarthritis. This paper comprehensively
      reviews the nature of GRF and presents arguments regarding its measurement in
      osteoarthritis research. 

PMID- 25392549
TI  - Warfarin therapy in a dog with acute arterial thrombosis and pyometra.
AB  - This report describes the presentation of acute arterial thrombosis causing
      triparesis in a 6-year-old female Chihuahua with pyometra and its successful
      management in combination with warfarin therapy. This is the first case report of
      a dog with arterial thrombosis associated with pyometra. 

PMID- 25392550
TI  - Atlanto-axial approach for cervical myelography in a Thoroughbred horse with
      complete fusion of the atlanto-occipital bones.
AB  - A 2-year-old Thoroughbred gelding with clinical signs localized to the first 6
      spinal cord segments (C1 to C6) had complete fusion of the atlanto-occipital
      bones which precluded performing a routine myelogram. An ultrasound-assisted
      myelogram at the intervertebral space between the atlas and axis was successfully
      done and identified a marked extradural compressive myelopathy at the level of
      the atlas and axis, and axis and third cervical vertebrae. 

PMID- 25392551
TI  - Primary immune-mediated neutropenia in a cat.
AB  - An 18-month-old male castrated indoor Himalayan cat was presented for recurrent
      fever, lethargy, and uveitis. Persistent neutropenia was identified and tests for
      infectious disease and bone marrow cytology were performed. Primary immune
      mediated neutropenia was diagnosed and successfully treated. At the time of
      writing this report, 24 mo after the initial diagnosis. the patient was
      clinically normal and not receiving therapy. 

PMID- 25392552
TI  - Star gazing in a dog: atypical manifestation of upper gastrointestinal disease.
AB  - A Yorkshire terrier dog was presented for episodes of "star gazing" behavior
      expressed as upward raising of the head and neck extension with subsequent
      staring at the ceiling or sky. Erosive gastritis with reflux esophagitis was
      diagnosed. Treatment of these conditions was associated with resolution of the
      behavior, suggesting a causal link. 

PMID- 25392553
TI  - The use of alfaxalone and remifentanil total intravenous anesthesia in a dog
      undergoing a craniectomy for tumor resection.
AB  - A 7-year-old castrated border collie dog was anesthetised for surgical resection
      of a hippocampal mass. Anesthesia was maintained using a previously unreported
      TIVA protocol for craniectomy consisting of alfaxalone and remifentanil. Recovery
      was uneventful, and the patient was discharged from hospital. We describe the
      anesthetic management of this case. 

PMID- 25392554
TI  - Fatal diphenhydramine poisoning in a dog.
AB  - We report a fatal diphenhydramine poisoning of a 10-year-old, male poodle-cross
      dog with pre-existing conditions and suspected co-ingestion of ethanol. This case
      illustrates that diphenhydramine overdose can be fatal in certain circumstances
      and that analytical toxicology may play an important role in animal death
      investigations. 

PMID- 25392555
TI  - Fascioloides magna infection causing fatal pulmonary hemorrhage in a steer.
AB  - A feedlot steer died suddenly without exhibiting signs of clinical illness. Cysts
      containing Fascioloides magna were found in the liver and lung. Fatal pulmonary
      hemorrhage was associated with these flukes. Neither death nor clinical pulmonary
      disease has been previously attributed to infections of adult cattle by F. magna.

PMID- 25392556
TI  - Ileocecocolic volvulus in a German shepherd dog.
AB  - This report describes an ileocecocolic volvulus in a German shepherd dog with
      risk factors of previous abdominal surgeries and concurrent chronic enteropathy.
      Contrast-enhanced computed tomography (CT) with multiplanar reformatting was more
      sensitive than abdominal radiographs or ultrasound to obtain a diagnosis, because
      of the presence of a "whirl-sign" on CT. A combination of colopexy and cecopexy
      was succesfully used to treat the patient's condition. 

PMID- 25392557
TI  - A case of methicillin-resistant Staphylococcus pseudintermedius (MRSP) pyoderma
      in a Labrador retriever dog.
AB  - An 8-year-old, neutered male Labrador retriever dog with generalized pruritis had
      a history of recurring atopic dermatitis and superficial pyoderma. Cocci and
      yeast were found on cytology and methicillin-resistant Staphylococcus
      pseudintermedius was cultured. A regimen of marbofloxacin, dexamethasone,
      ketoconazole, and cyclosporine in addition to bathing with 2% chlorhexidine
      shampoo resulted in marked improvement. 

PMID- 25392558
TI  - How much does a vacation cost?

PMID- 25392559
TI  - Diagnostic ophthalmology.

PMID- 25392560
TI  - Nonlinear Dynamics of Neuronal Excitability, Oscillations, and Coincidence
      Detection.
AB  - We review some widely studied models and firing dynamics for neuronal systems,
      both at the single cell and network level, and dynamical systems techniques to
      study them. In particular, we focus on two topics in mathematical neuroscience
      that have attracted the attention of mathematicians for decades: single-cell
      excitability and bursting. We review the mathematical framework for three types
      of excitability and onset of repetitive firing behavior in single-neuron models
      and their relation with Hodgkin's classification in 1948 of repetitive firing
      properties. We discuss the mathematical dissection of bursting oscillations using
      fast/slow analysis and demonstrate the approach using single-cell and mean-field
      network models. Finally, we illustrate the properties of Type III excitability in
      which case repetitive firing for constant or slow inputs is absent. Rather,
      firing is in response only to rapid enough changes in the stimulus. Our case
      study involves neuronal computations for sound localization for which neurons in
      the auditory brain stem perform extraordinarily precise coincidence detection
      with submillisecond temporal resolution.

PMID- 25392561
TI  - Multi-Band Miniaturized Patch Antennas for a Compact, Shielded Microwave Breast
      Imaging Array.
AB  - We present a comprehensive study of a class of multi-band miniaturized patch
      antennas designed for use in a 3D enclosed sensor array for microwave breast
      imaging. Miniaturization and multi-band operation are achieved by loading the
      antenna with non-radiating slots at strategic locations along the patch. This
      results in symmetric radiation patterns and similar radiation characteristics at
      all frequencies of operation. Prototypes were fabricated and tested in a
      biocompatible immersion medium. Excellent agreement was obtained between
      simulations and measurements. The trade-off between miniaturization and radiation
      efficiency within this class of patch antennas is explored via a numerical
      analysis of the effects of the location and number of slots, as well as the
      thickness and permittivity of the dielectric substrate, on the resonant
      frequencies and gain. Additionally, we compare 3D quantitative microwave breast
      imaging performance achieved with two different enclosed arrays of slot-loaded
      miniaturized patch antennas. Simulated array measurements were obtained for a 3D
      anatomically realistic numerical breast phantom. The reconstructed breast images
      generated from miniaturized patch array data suggest that, for the realistic
      noise power levels assumed in this study, the variations in gain observed across
      this class of multi-band patch antennas do not significantly impact the overall
      image quality. We conclude that these miniaturized antennas are promising
      candidates as compact array elements for shielded, multi-frequency microwave
      breast imaging systems.

PMID- 25392562
TI  - Modified Solenoid Coil That Efficiently Produces High Amplitude AC Magnetic
      Fields With Enhanced Uniformity for Biomedical Applications.
AB  - In this paper, we describe a modified solenoid coil that efficiently generates
      high amplitude alternating magnetic fields (AMF) having field uniformity (<=10%)
      within a 125-cm3 volume of interest. Two-dimensional finite element analysis (2D
      FEA) was used to design a coil generating a targeted peak AMF amplitude along the
      coil axis of ~100 kA/m (peak-to-peak) at a frequency of 150 kHz while maintaining
      field uniformity to >90% of peak for a specified volume. This field uniformity
      was realized by forming the turns from cylindrical sections of copper plate and
      by adding flux concentrating rings to both ends of the coil. Following
      construction, the field profile along the axes of the coil was measured. An axial
      peak field value of 95.8 +/- 0.4 kA/m was measured with 650 V applied to the coil
      and was consistent with the calculated results. The region of axial field
      uniformity, defined as the distance over which field >=90% of peak, was also
      consistent with the simulated results. We describe the utility of such a device
      for calorimetric measurement of nanoparticle heating for cancer therapy and for
      magnetic fluid hyperthermia in small animal models of human cancer.

PMID- 25392563
TI  - Distance majorization and its applications.
AB  - The problem of minimizing a continuously differentiable convex function over an
      intersection of closed convex sets is ubiquitous in applied mathematics. It is
      particularly interesting when it is easy to project onto each separate set, but
      nontrivial to project onto their intersection. Algorithms based on Newton's
      method such as the interior point method are viable for small to medium-scale
      problems. However, modern applications in statistics, engineering, and machine
      learning are posing problems with potentially tens of thousands of parameters or
      more. We revisit this convex programming problem and propose an algorithm that
      scales well with dimensionality. Our proposal is an instance of a sequential
      unconstrained minimization technique and revolves around three ideas: the
      majorization-minimization principle, the classical penalty method for constrained
      optimization, and quasi-Newton acceleration of fixed-point algorithms. The
      performance of our distance majorization algorithms is illustrated in several
      applications.

PMID- 25392564
TI  - The Severity, Frequency, and Variety of Crime in Heroin-Dependent Prisoners
      Enrolled in a Buprenorphine Clinical Trial.
AB  - Data were obtained on four dimensions of criminal activity (frequency, variety,
      severity, and income) from male and female prisoners (N = 200) with
      preincarceration heroin dependence who participated in a randomized clinical
      trial of buprenorphine treatment. The article examines the above-mentioned
      dimensions of crime and their relationships with demographic characteristics,
      substance use, legitimate employment, drug treatment episodes, and psychological
      problems. Results largely show several important similarities to results on
      previous prison inmate cohorts with histories of heroin addiction, although the
      present sample may have more of a tendency toward violent crime than earlier
      cohorts of heroin-dependent offenders. This study's findings may have
      implications for the design of appropriate treatment interventions for prisoners
      with preincarceration heroin dependence that address not only substance use but
      also criminal activity.

PMID- 25392565
TI  - Social Capital and Human Mortality: Explaining the Rural Paradox with County
      Level Mortality Data.
AB  - The "rural paradox" refers to standardized mortality rates in rural areas that
      are unexpectedly low in view of well-known economic and infrastructural
      disadvantages there. We explore this paradox by incorporating social capital, a
      promising explanatory factor that has seldom been incorporated into residential
      mortality research. We do so while being attentive to spatial dependence, a
      statistical problem often ignored in mortality research. Analyzing data for
      counties in the contiguous United States, we find that: (1) the rural paradox is
      confirmed with both metro/non-metro and rural-urban continuum codes, (2) social
      capital significantly reduces the impacts of residence on mortality after
      controlling for race/ethnicity and socioeconomic covariates, (3) this attenuation
      is greater when a spatial perspective is imposed on the analysis, (4) social
      capital is negatively associated with mortality at the county level, and (5)
      spatial dependence is strongly in evidence. A spatial approach is necessary in
      county-level analyses such as ours to yield unbiased estimates and optimal model
      fit.

PMID- 25392566
TI  - Assessing the Significance of Cohort and Period Effects in Hierarchical Age
      Period-Cohort Models: Applications to Verbal Test Scores and Voter Turnout in
      U.S. Presidential Elections.
AB  - In recently developed hierarchical age-period-cohort (HAPC) models, inferential
      questions arise: How can one assess or judge the significance of estimates of
      individual cohort and period effects in such models? And how does one assess the
      overall statistical significance of the cohort and/or the period effects? Beyond
      statistical significance is the question of substantive significance. This paper
      addresses these questions. In the context of empirical applications of linear and
      generalized linear mixed-model specifications of HAPC models using data on verbal
      test scores and voter turnout in U.S. presidential elections, respectively, we
      describe a two-step approach and a set of guidelines for assessing statistical
      significance. The guidelines include assessments of patterns of effects and
      statistical tests both for the effects of individual cohorts and time periods as
      well as for entire sets of cohorts and periods. The empirical applications show
      strong evidence that trends in verbal test scores are primarily cohort driven,
      while voter turnout is primarily a period phenomenon.

PMID- 25392567
TI  - New insights into therapeutic strategies for the treatment of peritoneal
      fibrosis: learning from histochemical analyses of animal models.
AB  - Encapsulating peritoneal sclerosis (EPS) is a fatal complication that can occur
      in patients undergoing long-term peritoneal dialysis. It is characterized by
      bowel obstruction and marked sclerotic thickening of the peritoneal membrane.
      Although the mechanisms underlying the development of EPS are complex,
      angiogenesis, inflammation, and peritoneal fibrosis are known to be essential
      factors. Now, several animal models that exhibit EPS have pathophysiology similar
      to that of human EPS and have been proposed for use in research to provide
      insights into it. Recent histochemical methods also help us to understand the
      pathophysiology of EPS. Advances in basic research based on the findings in those
      animal models have enabled the development of several strategies for the
      prevention and treatment of EPS. We describe here interventional studies in some
      animal models for peritoneal fibrosis, one of the histological disorders findings
      characteristic to EPS, and we highlight the need for a sophisticated animal model
      that closely resembles human conditions. 

PMID- 25392568
TI  - Expression of p75(NGFR), a Proliferative and Basal Cell Marker, in the Buccal
      Mucosa Epithelium during Re-epithelialization.
AB  - We investigated the expression of p75(NGFR), a proliferative and basal cell
      marker, in the mouse buccal mucosa epithelium during wound healing in order to
      elucidate the role of epithelial stem cells. Epithelial defects were generated in
      the epithelium of the buccal mucosa of 6-week-old mice using CO2 laser
      irradiation. BrdU was immediately administered to mice following laser
      irradiation. They were then sacrificed after 1, 3, 7, and 14 days. Paraffin
      sections were prepared and the irradiated areas were analyzed using
      immunohistochemistry with anti-p75(NGFR), BrdU, PCNA, and CK14 antibodies. During
      re-epithelialization, PCNA (-)/p75(NGFR) (+) cells extended to the wound, which
      then closed, whereas PCNA (+)/p75(NGFR) (+) cells were not observed at the edge
      of the wound. In addition, p75(NGFR) (-)/CK14 (+), which reflected the presence
      of post-mitotic differentiating cells, was observed in the supra-basal layers of
      the extended epithelium. BrdU (+)/p75(NGFR) (+), which reflected the presence of
      epithelial stem cells, was detected sparsely in buccal basal epithelial cells
      after healing, and disappeared after 7 days. These results suggest that p75(NGFR)
      (+) keratinocytes are localized in the basal layer, which contains oral
      epithelial stem cells, and retain the ability to proliferate in order to
      regenerate the buccal mucosal epithelium. 

PMID- 25392569
TI  - A Histopathological Study of Multi-hormone Producing Proliferative Lesions in
      Estrogen-induced Rat Pituitary Prolactinoma.
AB  - Rats with estrogen-induced prolactin-producing pituitary adenoma (E2-PRLoma) have
      been employed as an animal model of human PRL-producing pituitary adenoma in a
      large number of studies. Presently, we found that long-term administration of
      estrogen to SD rats resulted in the development of E2-PRLomas, some of which
      included multi-hormone producing nodules. We herein report results of
      histopathological analyses of these lesions. PRLoma models were created in female
      SD rats by 22 weeks or longer administration of a controlled-release preparation
      of estradiol at a dose of 10 mg/kg/2 weeks. Ten of the 11 PRLoma model rats had
      proliferative nodular lesions composed of large eosinophilic cells like
      gonadotrophs inside the PRLoma. These lesions were positive for PRL, TSHbeta, and
      alpha subunits and were negative for GH, LHbeta, ACTH, and S-100. Double
      immunostaining revealed that these large eosinophilic cells showed coexpression
      of PRL and TSHbeta, PRL and alpha subunits, and TSHbeta and alpha subunits. Those
      results clarified that long-term estrogen administration to female SD rats
      induced multi-hormone producing neoplastic pituitary nodules that expressed PRL,
      TSHbeta, and alpha subunits. We studied these neoplastic nodules obtained by
      laser microdissection to acquire findings similar to those of the immuno
      histochemical analysis. We consider that this animal model is useful for
      pathogenesis analyses and therapeutic agent development concerning human multi
      hormone producing pituitary adenomas. 

PMID- 25392570
TI  - Expression of glucocorticoid receptor and coactivators in ependymal cells of male
      rats.
AB  - Glucocorticoid receptor (GR) is a ligand-activated nuclear receptor which is
      widely distributed in the brain. Many types of neurons and glial cells are known
      to express GR, but the expression of GR in ependymal cells has yet to be
      identified. The present study therefore was undertaken to determine whether
      ependymal cells express GR and coactivators of GR, such as steroid receptor
      coactivator 1 (SRC-1) and p300. GR immunoreactivity was found in cells
      immunopositive to vimentin, a marker of ependymal cells, around the third
      ventricle (3V), the lateral ventricle (LV), the cerebral aqueduct and the fourth
      ventricle (4V), whereas the expression of GR in vimentin-immunoreactive (ir)
      cells was significantly reduced by adrenalectomy (ADX) in male rats. Vimentin-ir
      cells also expressed both SRC-1 and p300 at around 3V, LV, the cerebral aqueduct
      and 4V. ADX had no effect on the expression of SRC-1 or p300 in vimentin-ir
      cells. These results suggest that glucocorticoid may exert effects on ependymal
      cells through binding to GR followed by association with SRC-1 and p300 to
      maintain brain environment under stressful conditions. 

PMID- 25392571
TI  - Notch signaling may be involved in the abnormal differentiation of epidermal
      keratinocytes in psoriasis.
AB  - Localization of each keratin isoform differs among epidermal layers.
      Proliferating basal cells synthesize keratin 14 (K14) and suprabasal cells
      express keratin 10 (K10) in normal skin. Notch signaling is essential for
      keratinocyte differentiation. Notch1 is expressed in all epidermal layers, Notch2
      in the basal cell layer and Notch3 in basal cell and spinous cell layers in
      normal epidermis. It has been poorly elucidated how localization and expression
      levels of Notch molecules are related to epidermal molecular markers K10 and K14
      in psoriatic skin with abnormal differentiation of epidermal tissue. This study
      aimed to investigate the relationship between abnormal differentiation of
      epidermal cells in psoriatic skin and expression of Notch molecules. We
      investigated keratins (K14 and K10) and Notches (1, 2, 3 and 4) using
      immunohistochemistry in psoriatic skin (n=30) and normal skin (n=10). In normal
      skin, K14 and K10 were discretely observed in the basal cell layer and suprabasal
      layer, respectively. In psoriatic skin, K14 was expressed in the pan epidermal
      layer while it and K10 were co-expressed in some middle suprabasal layer cells.
      Notch1, 2, 3, and 4 localized in all epidermal layers in normal skin. In
      psoriatic skin, Notch1, 2, and 4 mainly localized in suprabasilar layers and
      Notch3 is lacalized in pan epidermal, suprabasilar, and basilar layers. Protein
      and mRNA of Notch1, 2, and 3 isoforms decreased in psoriatic epidermis compared
      with normal epidermis. These data suggest that decrements in these Notch
      molecules might cause aberrant expression of K10 and K14 leading to anomalous
      differentiation of the epidermis in psoriatic lesions. 

PMID- 25392572
TI  - Alcohol-Related Information in Multi-Component Interventions and College
      Students' Drinking Behavior.
AB  - Education-only interventions produce little change in drinking behaviors; but,
      multi-component prevention programs, which include alcohol information as one
      feature, can decrease drinking. This study examined the role of alcohol knowledge
      in a multi-component intervention previously found to reduce first-year female
      college students' alcohol consumption. Intervention and control group students
      completed pre and postintervention assessments of drinking behaviors, and a
      postintervention assessment of alcohol-knowledge. Intervention students
      outperformed control students on the measure of alcohol knowledge. However
      knowledge did not predict drinking outcomes for this group, and it was positively
      correlated with drinking behaviors for control students. The findings suggest
      that, although learning took place through the intervention, it was not the
      mechanism by which the intervention reduced drinking behaviors.

PMID- 25392574
TI  - RAPD and SSR based genetic diversity analysis of elite-2 set of synthetic
      hexaploid wheats.
AB  - BACKGROUND: Synthetic hexaploid wheats are artificially reconstituted hexaploid
      wheats that possess high genetic variation which could be utilized for the
      development of new improved wheat varieties. One such group of synthetic wheats
      is called the Elite-II set of synthetic wheats that are derived from crossing
      durum wheat with different Aegilops tauschii wheats. MATERIALS AND METHODS: In
      the current study genetic diversity was investigated among 18 Elite-II synthetic
      hexaploid wheat lines at DNA level. Two types of molecular markers i.e. RAPD and
      SSR were used for this purpose. RESULTS: Both types of markers proved useful in
      estimating the overall genetic diversity among these lines. Based on RAPD data
      range of genetic distances in these lines was from 0 to 100 percent. Seven D
      genome specific SSRs were also used to get further estimation of the genetic
      diversity contributed by Aegilops tauschii parent. On the basis of results
      obtained it is inferred that the Aegilops tauschi accessions used in the
      production of these synthetic lines were genetically different and they
      contributed to the enhancement of genetic variation in the synthetic lines. These
      results could be helpful for future genome mapping programs. CONCLUSION: The
      overall extensive genitive diversity indicates that these lines are good
      candidates for development of improved wheat varieties by crossing with
      cultivated wheat varieties.

PMID- 25392573
TI  - The anti-oxidant effects of ginger and cinnamon on spermatogenesis dys-function
      of diabetes rats.
AB  - BACKGROUND: Diabetes rats have been linked to reproductive dysfunction and plant
      medicine has been shown to be effective in its treatment. Antioxidants have
      distinctive effects on spermatogenesis, sperm biology and oxidative stress, and
      changes in anti-oxidant capacity are considered to be involved in the
      pathogenesis of chronic diabetes mellitus. Ginger and cinnamon are strong anti
      oxidants and have been shown to reduce oxidative stress in the long-term
      treatment of streptozotocin (STZ)-induced diabetes in animal models. The present
      study examined the influence of combined ginger and cinnamon on spermatogenesis
      in STZ-induced diabetes in male Wistar rats. MATERIALS AND METHODS: Animals (n =
      80) were allocated randomly into eight groups, 10 each: Group 1: Control rats
      given only 5cc Normal saline (0.9% NaCl) daily;Group2: rats received ginger
      (100mg/kg/rat) daily; Group 3: rats received cinnamon (75mg/kg) daily; Group 4:
      rats received ginger and cinnamon, (100mg/kg/rat ginger and 75mg/kg cinnamon)
      daily; Group 5: Diabetic control rats received only normal saline. Group 6:
      Diabetic rats received 100mg/kg/day ginger; Group 7: Diabetic rats received 75mg
      /kg/ day cinnamon; Group 8: Diabetic rats received ginger and cinnamon
      (100mg/kg/day and 75mg/kg /day). Diabetes was induced with 55 mg/kg, single intra
      peritoneal injection of STZ in all groups. At the end of the experiment (56th
      day), blood samples were taken for determination of testosterone, LH,FSH, total
      anti-oxidant capacity, and levels of malondialdehyde, SOD, Catalase and GPX. All
      rats were euthanized, testes were dissected out and spermatozoa were collected
      from the epididymis for analysis. RESULTS: Sperm numbers, percentages of sperm
      viability and motility, and total serum testosterone increased in ginger and
      cinnamon and combined ginger and cinnamon treated diabetic rats compared with
      control groups. Serum testosterone, LH and FSH were higher compared to control
      group and also serum anti-oxidants (TAC, SOD, GPX and catalase) all were
      increased at the end of treatment. Combined ginger and cinnamon showed more
      intense increase in all parameters compare to ginger and cinnamon alone. Most of
      the results were significant (P<0.05). CONCLUSION: We concluded that combined
      ginger and cinnamon have significant beneficial effects on the sperm viability,
      motility, and serum total testosterone, LH,FSH and serum anti-oxidants' level and
      could be effective for maintaining healthy sperm parameters and male reproductive
      function in diabetics.

PMID- 25392575
TI  - Anti-oxidant effects of pomegranate juice on Saccharomyces cerevisiae cell
      growth.
AB  - BACKGROUND: Pomegranate juice has a number of positive effects on both human and
      animal subjects. MATERIAL AND METHODS: Four groups were used in this study. i:
      Control group, ii: H2O2 group, iii: Pomegranate juice (PJ) group and iv: PJ +
      H2O2 group. Following the sterilization method for pomegranate juice (10%) and
      H2O2 (6% v/v), Saccharomyces cerevisiae cultures were added and the cultivation
      incubated at 35 degrees C for 72 hours. Fatty acids and vitamin concentrations
      were measured using HPLC and GC and the total protein bands profile were
      determined by SDS-PAGE. RESULTS: According to our results statistically
      significant differences have been determined among the study groups in terms of
      fatty acids and vitamin (p<0,05). Fatty acid synthesis, vitamin control and cell
      density increased in groups to which PJ was given in comparison with the control
      group (p<0,05). Pomegranate juice increased vitamins, fatty acids and total
      protein expression in Saccharomyces cerevisiae in comparison with the control.
      CONCLUSION: Pomegranate juice has a positive effect on fatty acid, vitamin and
      protein synthesis by Saccharomyces cerevisiae. Accordingly, we believe that it
      has significantly decreased oxidative damage thereby making a positive impact on
      yeast development.

PMID- 25392576
TI  - Chemical composition profiling and antifungal activity of the essential oil and
      plant extracts of Mesembryanthemum edule (L.) bolus leaves.
AB  - BACKGROUND: Essential oil from Mesembryanthemum edule leaves have been used by
      the Eastern Cape traditional healers for the treatment of respiratory tract
      infections, tuberculosis, dysentery, diabetic mellitus, laryngitis and vaginal
      infections. The investigation of bioactive compounds in the essential oil of this
      plant could help to verify the efficacy of the plant in the management or
      treatment of these illnesses. MATERIALS AND METHODS: Various concentrations of
      the hydro-distilled essential oil, ranging from 0.005-5 mg/ml, were tested
      against some fungal strains, using the micro-dilution method. Minimum inhibitory
      activity was compared with four other different crude extracts of hexane,
      acetone, ethanol and aqueous samples from the same plant. The chemical
      composition of the essential oil, hexane, acetone and ethanol extracts was
      determined using GC-MS. RESULTS: GC/MS analysis of the essential oil resulted in
      the identification of 28 compounds, representing 99.99% of the total oil.
      Phytoconstituents of hexane, acetone and ethanol extracts yielded a total peak
      chromatogram of fifty nine compounds. A total amount of 10.6% and 36.61% of the
      constituents were obtained as monoterpenes and oxygenated monoterpenes.
      Sesquiterpene hydrocarbons (3.58%) were relatively low compared to the oxygenated
      sesquiterpenes (9.28%), while the major concentrated diterpenes and oxygenated
      diterpenes were 1.43% and 19.24 %, respectively and phytol 12.41%. Total amount
      of fatty acids and their methyl esters content, present in the oil extract, were
      found to be 19.25 %. Antifungal activity of the oil extract and four solvent
      extracts were tested against five pathogenic fungal strains. The oil extract
      showed antifungal activity against Candida albican, Candida krusei, Candida
      rugosa, Candida glabrata and Cryptococcus neoformans with MIC ranges of 0.02 0.31
      mg/ml. Hexane extract was active against the five fungal strains with MICs
      ranging between 0.02-1.25 mg/ml. Acetone extracts were active against C. krusei
      only at 0.04mg/ml. No appreciable antifungal activity was found in either ethanol
      or water extracts when compared with commercial antibiotics. CONCLUSION: The
      profile of chemical constituents found in M. edule essential oil and its
      antifungal properties support the use of M. edule by traditional healers as well
      as in the pharmaceutical and food industries as a natural antibiotic and food
      preservative.

PMID- 25392577
TI  - Biocompatibility of bio based calcium carbonate nanocrystals aragonite polymorph
      on NIH 3T3 fibroblast cell line.
AB  - BACKGROUND: Currently, there has been extensive research interest for inorganic
      nanocrystals such as calcium phosphate, iron oxide, silicone, carbon nanotube and
      layered double hydroxide as a drug delivery system especially in cancer therapy.
      However, toxicological screening of such particles is paramount importance before
      use as delivery carrier. In this study we examine the biocompatibility of CaCO3
      nanocrystal on NIH 3T3 cell line. MATERIAL AND METHODS: Transmission and field
      emission scanning electron microscopy (TEM and FESEM) were used for the
      characterisation of CaCO3 nanocrystals. Cytotoxicity and genotoxic effect of
      calcium carbonate nanocrystals in cultured mouse embryonic fibroblast NIH 3T3
      cell line using various bioassays including MTT, and Neutral red/Trypan blue
      double-staining assays. LDH, BrdU and reactive oxygen species were used for
      toxicity analysis. Cellular morphology was examined by scanning electron
      microscopy (SEM) and confocal fluorescence microscope. RESULTS: The outcome of
      the analyses revealed a clear rod-shaped aragonite polymorph of calcium carbonate
      nanocrystal. The analysed cytotoxic and genotoxicity of CaCO3 nanocrystal on NIH
      3T3 cells using different bioassays revealed no significance differences as
      compared to control. A slight decrease in cell viability was noticed when the
      cells were exposed to higher concentrations of 200 to 400 ug/ml, while increase
      in ROS generation and LDH released at 200 and 400 ug/ml was observed.
      CONCLUSIONS: The study has shown that CaCO3 nanocrystal is biocompatible and non
      toxic to NIH 3T3 fibroblast cells. The analysed results offer a promising
      potential of CaCO3 nanocrystal for the development of intracellular drugs, genes
      and other macromolecule delivery systems.

PMID- 25392578
TI  - Ultrastructure and elemental analysis of Hypoxis hemerocallidea: a multipurpose
      medicinal plant.
AB  - BACKGROUND: Herbal medicine is a popular means of medical management in some
      parts of the world especially in Africa. Hypoxis hemerocallidea Fisch.C.A.Mey. &
      Ave-Lall, also known as African potato of the Hypoxidaecae family, is one of the
      medicinal plants that have enjoyed long usage as an herbal medicine in South
      Africa. In this study, the morphology and elemental constituents of H.
      hemerocallidea leaf was investigated to correlate the functional role of the
      ultrastructure in the production of therapeutic compounds. MATERIALS AND METHODS:
      Fresh leaves of H. hemerocallidea were prepared for analysis using standard
      methods. The ultrastructure and crystal deposits of the plant were assessed using
      scanning electron microscopy (SEM), and energy dispersive x-ray (EDX). RESULTS:
      It was observed that the leaves were characterised by multicelullar glandular and
      non glandular trichomes which are sparsely distributed over the entire surfaces.
      The glandular trichomes (GTs) in H. hemerocallidea leaf have boulbous heads which
      are probably filled with secretions, while the non glandular trichomes were long,
      fibrous and sparse. EDX-SEM of Hypoxis hemerocallidea leaf revealed that carbon,
      oxygen, nitrogen and silicon are the major components of the deposits, while
      other elements such as iron, sulphur, sodium, calcium, magnesium, potassium,
      manganese, iodine, chromium and iodine were present in small but variable
      amounts. CONCLUSION: The presence of these elements which are crucial to
      maintaining good health, in addition to other bioactive constituents might be
      accountable for the multipurpose therapeutic uses of Hypoxis hemerocallidea in
      the treatment of cancers, HIV/AIDS related diseases, urinary tract infections,
      cardiovascular disorders, diabetes and other chronic ailments of humans.

PMID- 25392579
TI  - Laxative activities of Cassia sieberiana and Senna obtusifolia.
AB  - BACKGROUND: The root and stem bark of Cassia sieberiana DC. (Caesalpiniaceae) and
      the root of Senna obtusifolia (Linn) Irwin and Barneby (Caesalpiniaceae), used
      for constipation in Nigeria, were assayed for laxative properties in male albino
      rats using the official senna leaf (Senna alexandrina Mill. family
      Caesalpiniaceae) as the reference standard. This is with a view to finding
      alternative laxative drug to official senna which is presently being imported
      into Nigeria from the United Kingdom. MATERIALS AND METHODS: The mean percentage
      of wet faeces in rats, an indication of laxative activity, were obtained using
      established methods. The laxative activity was established at 500 mg/kg after the
      infusion of the drug was orally administered on male albino rats following
      established methods while a set of data was analyzed at 95 % confidence level.
      RESULTS: At 500 mg/kg, Senna obtusifolia root gave about 45 % wet faeces while
      Cassia sieberiana root gave about 40 % wet faeces while at the highest dose of
      700 mg/kg, they produced 60 % and 38 % wet faeces, respectively. At these two
      doses, the official Senna gave 50.6 % and 66 % wet faeces, respectively. Thus, S.
      obtusifolia and C. sieberiana roots exhibited 89 % and 80 % of the potency of S.
      alexandrina (the official drug), respectively. The analysis of variance revealed
      a significant statistical difference in the levels of wet faeces produced by rats
      dosed with C. sieberiana root. CONCLUSION: The results have shown that the roots
      of the two species could be developed as mild laxative drugs for children and
      pregnant women for whom the official senna will be contraindicated.

PMID- 25392580
TI  - Phytotherapeutic activity of Euphorbia cyparissias extracts on Ixodidae (Acari)
      female ticks.
AB  - BACKGROUND: Given its numerous biologically active components, Euphorbiaceae has
      been found to be a large plant family and polyvalent with quite interesting
      therapeutic activity that can be studied. MATERIALS AND METHODS: The ixodicidal
      activity of Euphorbia cyparissias extracts was studied in vitro and in vivo.
      Tested concentrations were 10, 5, 2, 1, 0.5 and 0.25%. RESULTS: For the in vitro
      study, conducted on field-collected female specimens of Dermacentor marginatus
      and Haemaphysalis punctata, the efficacy results showed that the ticks died after
      exposure in the case of 10, 5, and 2% tincture concentrations. The effects
      appeared after 30 minutes and became more visible 120 minutes after each
      exposure. The statistical differences regarding the used concentrations were
      found to be: F = 6.51, df = 5, P < 0.001. The in vivo study of the efficacy of E.
      cyparissias concentrations was performed on 35 naturally infested sheep and on 30
      bovines parasitized with Ixodes ricinus, sprayed with tincture and glycerinate
      dilutions (bovines) on days 0 and 7. The results revealed detrimental effects on
      the survivability of female ticks, the most prominent being the reduction of
      their movement capacity. In sheep in vivo efficiency observed within 24 hrs
      varied, between 1 and 23% for D. marginatus and between 7 and 27% for H. punctata
      and respectively between 2 and 53% after 24 hrs, for I. ricinus, comparable
      effects being also found 72 hrs after the second administration of Euphorbia
      extracts. CONCLUSION: Extracts from E. cyparissias may be used, with results, as
      an ecologic alternative tick control management method, being a cheap solution,
      with a sizeable role in reducing the use of synthetic and/or other harming and
      resistance source ixodicidal conditionings.

PMID- 25392581
TI  - The inhibitory activity of the extracts of popular medicinal herbs on CYP1A2,
      2C9, 2C19 and 3A4 and the implications for herb-drug interaction.
AB  - BACKGROUND: Studies have suggested an increasing practice of concurrent herb-drug
      consumption. One of the major clinical risks of such concomitant herb-drug use is
      pharmacokinetic herb-drug interaction (HDI). This is brought about by the ability
      of phytochemicals to inhibit or induce the activity of metabolic enzymes. The aim
      of this study was to investigate the potential of the crude aqueous extracts of
      three popular medicinal herbs used in South Africa to inhibit major cytochrome
      P450 (CYP) enzymes. MATERIALS AND METHODS: The extracts of Bowiea volubilis,
      Spirostachys africana and Tulbaghia violacea were incubated with human liver
      microsomes (HLM) to monitor the phenacetin O-deethylation, diclofenac 4'
      hydroxylation, S-mephenytoin 4'-hydroxylation and testosterone 6beta
      hydroxylation as respective probe reactions for CYP1A2, CYP2C9, CYP2C19 and
      CYP3A4. The inhibitory activity, where observed, was profiled against the extract
      concentration. RESULTS: Extracts of Bowiea volubilis inhibited the metabolic
      activity of CYP1A2 and CYP3A4 with IC50 values of 92.3 +/- 5.5 ug/mL and 8.1 +/-
      0.6 ug/mL respectively. Similar observation with Spirostachys africana showed
      inhibitory activity against CYP1A2 and CYP3A4 with respective IC50 values of 14.3
      +/- 0.6 ug/mL and 47.4 +/- 2.4 ug/mL. Tulbaghia violacea demonstrated relatively
      weak inhibitory activity against CYP1A2 (767.4 +/- 10.8 ug/mL) and CYP2C9 (921 +/
      15.3 ug/mL). CONCLUSION: The results suggest the potential for HDI between the
      herbs and the substrates of the affected enzymes, if sufficient in vivo
      concentration is attained.

PMID- 25392582
TI  - Cytotoxicity of selected medicinal plants used in Mt. Frere District, South
      Africa.
AB  - BACKGROUND: In South African traditional medicine, some are plants known to
      combat pediatric diseases and are commonly used by traditional healers. The aim
      was to evaluate cytotoxicity effects of plants. MATERIALS AND METHODS: The ground
      plant material was exhaustively extracted using methanol, acetone and water
      separately for 72 hrs. These organic solvents were removed from filtrates using a
      rotavapour. Stock solutions were prepared at 40 mg/ml Dimethyl sulfoxide (DMSO)
      and test solutions were transferred into vials and 10 brine shrimps introduced in
      each. The number of dead shrimps was counted to ascertain toxicity. Ten A. salina
      nauplii (larva) were transferred into each sample vial and filtered brine
      solution was added to make 5 ml. The nauplii were counted macroscopically in the
      stem of the pipette against a lighted background. A drop of dry yeast suspension
      was added as food to each vial. Probit analysis was used to determine the
      concentration at which lethality to brine shrimp represents 50 % (LC50). RESULTS:
      All the tested extracts showed that the concentration is directly proportional to
      death of brine shrimps. Fifty percent lethality (LC50) of the tested crude
      extract ranged between 4.1 and 4.6 ug/ml with methanol extract of B. abyssinica
      being the lowest and T. acutiloba the highest. CONCLUSION: This study revealed
      that 100% of plant crude extracts screened for activity against Artemisia salina
      larvae showed strong cytotoxicity below 10 ug/ml and plant species with LC50
      values < 1000 ug/ml may not make good paediatric remedies due to their inherent
      toxicity.

PMID- 25392583
TI  - Chemopreventive activity of methanol extract of Melastoma malabathricum leaves in
      DMBA-induced mouse skin carcinogenesis.
AB  - BACKGROUND: Melastoma malabathricum L. Smith (family Melastomaceae) is a shrub
      that has been used by the Malay practitioners of traditional medicine to treat
      various types of ailments. The present study aimed to determine the
      chemopreventive activity of methanol extract of M. malabathricum leaves (MEMM)
      using the standard 7,12-dimethylbenz(alpha)anthracene (DMBA)/croton oil-induced
      mouse skin carcinogenesis model. MATERIALS AND METHODS: In the initiation phase,
      the mice received a single dose of 100ul/100 ug DMBA (group I-V) or 100ul acetone
      (group VI) topically on the dorsal shaved skin area followed by the promotion
      phase involving treatment with the respective test solutions (100 ul of acetone,
      10 mg/kg curcumin or MEMM (30, 100 and 300mg/kg)) for 30 min followed by the
      topical application of tumour promoter (100ul croton oil). Tumors were examined
      weekly and the experiment lasted for 15 weeks. RESULTS: MEMM and curcumin
      significantly (p<0.05) reduced the tumour burden, tumour incidence and tumour
      volume, which were further supported by the histopathological findings.
      CONCLUSION: MEMM demonstrated chemoprevention possibly via its antioxidant and
      anti-inflammatory activities, and the action of flavonoids like quercitrin.

PMID- 25392584
TI  - Foliar micro-morphology of Gasteria bicolor haw. (Asphodelaceae) from South
      Africa.
AB  - BACKGROUND: The succulent genus, Gasteria, which comprises 16 species, is endemic
      to South Africa and has its main centre of distribution in the Savanna Region of
      the Eastern Cape. Whereas G. bicolor has been investigated phyto-chemically and
      pharmacologically, not much data concerning the anatomical and micro
      morphological features can be found in literature. MATERIALS AND METHODS: This
      study was undertaken, using light and scanning electron microscopy to obtain
      information on the micro-morphological features of this important medicinal plant
      to facilitate its identification and authentication. The elemental composition of
      the leaf was determined by energy dispersive X-ray spectroscopy (EDXS). RESULTS:
      The epidermal cells are either hexagonal or pentagonal in form, and are compactly
      arranged with undulate anti-clinal cell walls. The epidermal cell width was
      approximately 50 um. Stomata apertures are elliptical and the upper epidermis of
      the leaf has paracytic stomata which are slightly raised above the epidermal
      surface with 4 to 5 subsidiary cells surrounding each stoma. Based on the EDXS
      microanalysis, the mineral crystals present at the level of the mesophyll of G.
      bicolor were probably mixtures of calcium oxalate, calcium sulphate and silica.
      CONCLUSION: The co-occurrence of aluminum suggests the potential role of the
      crystals in detoxification of aluminum and heavy metals, as reported previously.

PMID- 25392585
TI  - Pigmentation and dermal conservative effects of the astonishing algae Sargassum
      polycystum and Padina tenuis on guinea pigs, human epidermal melanocytes (HEM)
      and Chang cells.
AB  - BACKGROUND: The preference for a fairer skin-tone has become a common trend among
      both men and women around the world. In this study, seaweeds Sargassum polycystum
      and Padina tenuis were investigated for their in vitro and in vivo potentials in
      working as skin whitening agents. Seaweed has been used as a revolutionary skin
      repairing agent in both traditional and modern preparations. The high antioxidant
      content is one of the prime reasons for its potent action. It has been employed
      in traditional Chinese and Japanese medicine. For centuries, most medical
      practitioners in the Asian cultures have known seaweed as an organic source of
      vitamins, minerals, fatty acids like omega-3 and omega-6 and antioxidants. The
      present objective of the study was to evaluate the potent dermal protective
      effect of the two seaweeds Sargassum polycystum and Padina tenuis on human cell
      lines and guinea pigs. MATERIAL AND METHODS: Seaweeds were extracted with ethanol
      and further fractionated with hexane, ethyl acetate and water. The extracts were
      tested for mushroom tyrosinase inhibitory activity, cytotoxicity in human
      epidermal melanocyte (HEM), and Chang cells. Extracts with potent
      melanocytotoxicity were formulated into cosmetic cream and tested on guinea pigs
      in dermal irritation tests and de-pigmentation assessments. RESULTS: Both
      Sargassum polycystum and Padina tenuis seaweeds showed significant inhibitory
      effect on mushroom tyrosinase in the concentration tested. SPEt showed most
      potent cytotoxicity on HEM (IC50 of 36ug/ml), followed by SPHF (65ug/ml), and
      PTHF (78.5ug/ml). SPHF and SPEt reduced melanin content in skin of guinea pigs
      when assessed histologically. CONCLUSION: SPEt, SPHF and PTHF were able to
      inhibit HEM proliferation in vitro, with SPHF being most potent and did not cause
      any dermal irritation in guinea pigs. The results obtained indicate that SPHF is
      a promising pharmacological or cosmetic agent.

PMID- 25392586
TI  - Larvicidal properties of simalikalactone D from Quassia africana (Simaroubaceae)
      Baill and Baill, on the malaria vector Anopheles gambiae.
AB  - BACKGROUND: Botanical and microbial insecticides have been increasingly used for
      the control of mosquito given their efficacy and documented nontoxic effects on
      non-target organisms. The discovery of new insecticides is imperative because of
      the development of resistance by the mosquitoes to the readily available
      insecticides. The aim of this study was therefore to isolate and characterize
      compounds from a local medicinal plant, Quassia africana Baill and Baill
      (Simaroubaceae) that were toxic to Anopheles gambiae. MATERIAL AND METHODS: The
      methanol extracts of the leaves, stem and roots of Quassia africana were tested
      against fourth instar larvae of An. gambiae. The root extract was partitioned
      into hexane, chloroform and ethyl acetate and the resulting extracts screened for
      larvicidal properties. The extracts and the fraction with the highest bioactivity
      were subjected to repeated column chromatography and isolated compounds evaluated
      for potential toxicity to An. gambiae larvae. The structure of the active
      compound was elucidated using spectroscopic techniques. The root extract showed
      the strongest activity profile (LC50 = 17.58 ug/mL). The chloroform soluble
      fraction obtained after partitioning the crude extract into solvents based on
      polarities was the most toxic. Further bio-activity-guided chromatographic
      separation of the chloroform fraction of the root extract led to the
      identification and isolation of a simalikalactone D as the larvicidal compound in
      Q. africana (LC50 = 1.25 ug/mL). RESULTS: Results suggest that Q. africana may
      serve as a source for vector control agent for malaria. CONCLUSION:
      Simalikalactone D was identified as the larvicidal compound in Q. africana (LC50
      = 1.25 ug/mL).

PMID- 25392587
TI  - Remedial applications of silencing ribonucleic acids and modalities for its
      delivery to the kidneys--a review.
AB  - BACKGROUND: The Kidney has been the target organ for the delivery of silencing
      ribonucleic acids (silencing RNA) administered systemically in comparison to
      other body tissues. MATERIALS AND METHOD: In this review, we discussed different
      approaches made to delivering proteins to the kidneys in different conditions
      like normal and pathological defects. Data from clinical experiments have been
      used to discuss and support the administration of silencing RNA for the treatment
      of kidney diseases. RESULTS: Results were achieved using the available genome
      wide RNA libraries. CONCLUSION: The research results are helpful in application
      to 3D and conventional models to find the involvement of signal pathways in
      kidney diseases.

PMID- 25392588
TI  - Effects of Ciji Hua'ai Baosheng granule formula (CHBGF) on life time, pathology,
      peripheral blood cells of tumor chemotherapy model mouse with H22 hepatoma
      carcinoma cells.
AB  - BACKGROUND: Ciji Hua'ai Baosheng Granule Formula (CHBGF) is a traditional Chinese
      empirical formula that can help the tumor patients who have received chemotherapy
      antagonize the toxin and side-effects so as to improve and prolong the life. This
      study is to evaluate the effects of CHBGF on improving life quality in terms of
      survival time, pathology of tumor tissue and ameliorating peripheral blood cells
      in mouse chemotherapy model with subcutaneous transplanted tumor or ascitic tumor
      of H22 hepatoma carcinoma cells at an overall level. MATERIALS AND METHODS: 71
      mice among the 92 Kunming mice were injected subcutaneously into the right
      anterior armpit with H22 hepatoma carcinoma cells, after 7 days, which had formed
      tumors and were used peritoneal injection of Cytoxan (CTX) (200mg/kg) to
      establish the mouse chemotherapy model with transplanted tumor, and then which
      were commensurately divided into 8 groups by random digits table. 21 mice were
      injected into peritoneal cavity to use CTX and the same method to establish the
      model. The groups for evaluating the effects on the survival time were the model,
      CHBGF and positive control group respectively with 7 mice in each group. The
      groups for evaluating the effects on anti-cancer were the model group, three
      treatment groups and positive control group with 10 mice in each group. The
      survival-time-observing groups were given intragastric administration of normal
      saline, CHBGF (64g/kg) once a day, and peritoneal injection of 5-Fluorouracil
      (25mg/kg) once every other day respectively. The survival time of each group was
      observed. The five anti-cancer-observing groups were given intragastric
      administration of normal saline, CHBGF (64g/kg, 32g/kg and 16g/kg) once a day,
      and peritoneal injection of 5-Fluorouracil (25mg/kg) once every other day
      respectively. After treatment for 21 days, the transplanted tumors were peeled
      off. Blood was collected through pricking eyeball and analyzed by hematology
      analyzer. And postchemotherapy transplanted tumor inhibition ratios were
      calculated. Pathological changes of tumor tissues and blood smears were observed
      with light microscope. RESULTS: The life prolonging rate of CHBGF (64g/kg) group
      with transplanted tumor is 20.14%, and their survival time was longer than that
      of the 5-Fluorouracil group (P<0.05). Life prolonging rate of CHBGF (64g/kg)
      group with ascitic tumor is 64.15%, the survival time was longer than that of the
      model group (P<0.01) and the 5-Fluorouracil group (P<0.05). The growth of the
      transplanted tumor in model group was faster than that in CHBGF (64g/kg) group
      and 5-Fluorouracil group (P<0.05). The tumor average weight of the positive drug
      and the CHBGF (64g/kg, 32g/kg) groups was lighter than that of the model group
      (P<0.05 or P<0.01). The inhibition ratios of CHBGF (64g/kg, 32g/kg and 16g/kg)
      groups are 31.15%, 21.31%, and 13.11% respectively. Under light microscope, in
      the positive drug and three CHBGF groups the pathological deteriorated severity
      of tumor tissue observed was milder than that in the model group, the
      distribution of WBC in CHBGF groups was more obvious than that of the model and 5
      Fluorouracil groups. The WBC and PLT decrease in CHBGF (64g/kg, 32g/kg and
      16g/kg) groups is less than the model and the 5-Fluorouracil group (P<0.05 or
      P<0.01), the number of RBC and HGB just in the CHBGF (64g/kg) group was more than
      that of the model group or the 5-Fluorouracil group (P<0.05). CONCLUSION: Ciji
      Hua'ai Baosheng Granule Formula can prolong the survival time of the mice
      chemotherapy model of both subcutaneous transplanted tumor and ascitic tumor of
      H22 hepatoma carcinoma cells, has some determinate inhibitory effects on the
      growth of subcutaneous transplanted tumor chemo-treated, and has the therapeutic
      effect on antagonizing decrease of WBC and PLT caused by chemotherapy.

PMID- 25392589
TI  - Da-cheng-qi decoction, a traditional Chinese herbal formula, for intestinal
      obstruction: systematic review and meta-analysis.
AB  - BACKGROUND: This study was aimed at determining the effects and safety of Da
      Cheng-Qi decoction (DCQD) or DCQD combined with conservative therapy in patients
      with intestinal obstruction. MATERIALS AND METHODS: PubMed, EMBASE, Cochrane
      Controlled Trials Register, and several other databases were searched. Randomised
      controlled trials (RCTs) of DCQD or DCQD plus conservative therapy in patients
      with intestinal obstruction were eligible. Therapeutic effect was estimated by
      the improvement of clinical manifestations and diagnostic imaging;
      dichotomous/ordinal data assessment of overall response to therapy, adverse
      effects; or continuous variable were identified, including time to first bowel
      movement, time to first flatus, length of hospital stay. RESULTS: Sixty eligible
      RCTs including 6,095 patients were identified. Response rate: (1) DCQD versus
      conservative therapy (6 RCTs, 361 patients, RR of respond =1.13; 95% CI 0.97 to
      1.31). (2) DCQD plus conservative therapy versus conservative therapy (48 RCTs,
      4,916 patients, RR of respond =1.25 which favoured DCQD plus conservative
      therapy; 95% CI 1.20 to 1.30). Treatment effect remained similar when RCTs at
      high risk of bias were excluded. Time to first flatus postoperatively: (1) DCQD
      versus conservative therapy (2 RCTs, 240 patients, SMD=-3.65; 95% CI -8.17 to
      0.87). (2) DCQD plus conservative therapy versus conservative therapy (11 RCTs,
      1,040 patients, SMD=-2.09 which favoured DCQD plus conservative therapy; 95% CI 
      3.04 to -1.15). CONCLUSION: DCQD combined with conservative therapy may increase
      the success rate of conservative therapy for intestinal obstruction significantly
      and can shorten the duration of postoperative ileus in patients undergoing
      abdominal surgery compared with conservative therapy alone.

PMID- 25392590
TI  - Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the
      rat bladder contractility.
AB  - BACKGROUND: Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its
      capsular fruit is commonly used in traditional Chinese medicine for the treatment
      of different urinary incontinence symptoms including frequency, urgency and
      nocturia. These symptoms are similar to the overactive bladder syndrome. In our
      lab, we found that the 95% ethanol extract of the capsular fruits exhibited
      significant anti-muscarinic activity. Some constituents in capsular fruits
      including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g.,
      yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are
      regarded as representative chemicals with putative pharmacological activities.
      OBJECTIVE: This study aimed to evaluate the in vitro antagonistic actions of
      izalpinin on carbachol-induced contraction of the rat detrusor muscle. MATERIALS
      AND METHODS: In vitro inhibition of rat detrusor contractile response to
      carbachol was used to study the functional activity of izalpinin. The isolated
      detrusor strips of rats were mounted in organ baths containing oxygenated Krebs'
      solution. The cumulative consecutive concentration-response curves to carbachol
      evoked contractions in strips of rat bladder were obtained. RESULTS: Carbachol
      induced concentration-dependent contractions of isolated rat bladder detrusor
      strips. The vehicle DMSO had no impact on the contraction response. The
      contraction effects were concentration-dependently antagonized by izalpinin, with
      a mean EC50 value of 0.35 uM. The corresponding cumulative agonist concentration
      response curves shifted right-ward. CONCLUSIONS: Izalpinin exhibits inhibitory
      role of muscarinic receptor-related detrusor contractile activity, and it may be
      a promising lead compound to treat overactive bladder.

PMID- 25392591
TI  - Prevalence and acceptability of male circumcision in South Africa.
AB  - BACKGROUND: The objectives of the current national study were to determine the
      rates of self-reported circumcision among South African men and, more
      importantly, evaluate the acceptability of male circumcision in South Africa by
      uncircumcised adult men and all adult women. MATERIALS AND METHODS: The study
      based on a population-based survey included a nationally representative subgroup
      of 6654 men aged 15 years and older who where included in the analysis on male
      circumcision prevalence, and a subgroup of 6796 women aged 15 to 49 years who
      were included in the analysis on male circumcision acceptance. RESULTS: An
      overall prevalence of self-reported male circumcision of 42.8% was found. Among
      the Black African population group the prevalence of male circumcision was 48.2%,
      32.1% were traditionally and 13.4% were medically circumcised. Among males not
      circumcised 45.7% of 15-24 years olds indicated that they would consider being
      circumcised compared to 28.3% among 25-49 years olds. In multivariate analysis
      among non-circumcised men Black African and Coloured population groups and having
      heard of the HIV protective effect of male circumcision were significant
      predictors for male circumcision acceptability, and among women with a non
      circumcised sexual partner, Black African and Coloured population groups and
      higher education were predictors for male circumcision acceptability. CONCLUSION:
      The study found high rates and high acceptability of male circumcision. Findings
      associated with the acceptability of male circumcision can be used to increase
      awareness of the benefits of male circumcision for HIV prevention.

PMID- 25392592
TI  - Is ingestion of Thasus gigas (Xamues) an alimentary culture or an auxiliary
      treatment for type II diabetes?
AB  - BACKGROUND: Diabetes is a disease characterized by high blood glucose levels that
      result from the body's inability to produce and/or use insulin. Among different
      types of diabetes, type II diabetes is the most common. This work studied the
      causes and effects of Thasus gigas on the population of Actopan, Hidalgo
      regarding its ingestion and utility in the treatment of type II diabetes.
      MATERIAL AND METHODS: An exploratory study was carried out based on a survey
      conducted among the residents of Actopan, Hidalgo suffering from diabetes
      mellitus (type II). In order to investigate the effect of the ingestion of
      insects "xohues" or "shamues", a study was conducted on 100 adults among the
      population of Actopan, Hidalgo in order to get information on Thasus gigas
      consumption. The study was designed to identify the relationships between its
      usage, effects on human health, the reasons for its consumption by the Actopan
      community; either for cultural matters or as an alternative treatment to manage
      type II diabetes. RESULTS: Of the 100 persons surveyed, 39 were diabetic, 29 made
      medical outpatient visits. Among these, 21 had eaten Xamues to manage their
      diabetes while 21.5% replaced their medical treatment with Xamues. Of the 53% of
      the people who ingested Xamues as an alternative for their disease, 13% abandoned
      their medical treatment while 33% consumed them for alimentary culture.
      CONCLUSION: People who have stopped attending medical checkups are at risk,
      because there is no evidence that ingestion of these insects can regulate blood
      glucose levels.

PMID- 25392593
TI  - Combinative effects of thanh hao miet giap thang (sweet wormwood and tortoise
      shell decoction) ingredients on antioxidative activity in vitro.
AB  - BACKGROUND: Traditional formulae usually exhibit therapeutic effects through the
      combinations of different ingredients. The purpose of this study was to
      investigate in vitro anti-oxidative activity of Thanh Hao Miet Giap Thang (THMGT)
      (Sweet Wormwood and Tortoise Shell Decoction) formula and the interactions of its
      ingredients leading to the overall anti-oxidative effect. MATERIALS AND METHODS:
      We prepared 31 combinations containing two to four of the five ingredients
      including Herba Artemisia apiacea L (HbA), Carapax Trionycis (Tryonix sinensis)
      (CT), Rhizoma Anemarrhenae (Anemarrhena asphodeloides) (RzA), Radix Rehmanniae
      (Rehmannia glutinosa Libosch) (RdR), Moutan Cortex (Paeonia suffruticosa) (MC).
      These combinations were tested for anti-oxidative activity using DCFH-DA and DPPH
      assays on Hep G2 cells. We also analyzed changes in expression of genes involved
      in antioxidant defense system including Nuclear Factor Erythroid-Derived 2-Like 2
      (NFE2L2), catalase (CAT), heme oxygenase-1 (HO-1), glutathione peroxidase (GPx),
      cytoplasmic superoxide dismutase (SOD1), mitochondrial superoxide dismutase
      (SOD2). RESULTS: The complete formula and all combinations containing Moutan
      Cortex showed high antioxidant activity in both radical solution-based chemical
      assay and cellular-based assay. On the contrary, Carapax Trionycis displayed
      inhibitory effect on the overall antioxidant activity when present in a
      combination, an effect clearly emphasized in cellular-based assay. Hep G2 cells
      treated with the formula showed increased gene expression of HO-1 and SOD2 while
      expression of CAT, SOD1, GPx was unchanged. CONCLUSION: Our results suggested
      that THMGT had anti-oxidative activity essentially through intrinsic reducing
      capacities and the overall activity of the formula resulted from enhancing and
      inhibiting interactions of ingredients.

PMID- 25392594
TI  - Evaluation of three medicinal plant extracts against Plasmodium falciparum and
      selected microganisms.
AB  - BACKGROUND: A great revival of scientific interests in drug discovery has been
      witnessed in recent years from medicinal plants for health maintenance. The aim
      of this work was to investigate three Nigerian medicinal plants collected in
      Nigeria for their in vitro antiplasmodial and antimicrobial activities. MATERIALS
      AND METHODS: Extracts obtained from parts of Persea americana, Jatropha podagrica
      and Picralima nitida and their fractions were evaluated for in vitro
      antiprotozoal and antimicrobial activity. RESULT: The methanol extract of P.
      nitida demonstrated activity against chloroquine-sensitive and chloroquine
      resistant P. falciparum clones with IC50 values of 6.3 and 6.0 ug/mL,
      respectively. Methanol and chloroform extracts of P. americana seed showed
      antifungal activity against Cryptococcus neoformans IC50 less than 8 and 8.211
      ug/mL respectively. Finally, the petroleum ether extract of P. americana had
      activity against methicillin-resistant Staphylococcus aureus (MRSA) with an IC50
      value of 8.7 ug/mL. CONCLUSION: The study revealed the antibacterial and
      antiplasmodial activities of the plants extracts at the tested concentrations.

PMID- 25392595
TI  - Phenolic composition, antioxidant capacity of Salvia verticcilata and effect on
      multidrug resistant bacteria by flow-cytometry.
AB  - BACKGROUND: Antioxidants are of great importance for preventing oxidative stress
      that may cause several degenerative diseases. Studies have indicated
      phytochemicals have high free-radical scavenging activity, which helps to reduce
      the risk of chronic diseases. The aim of the present study is the determination
      of antioxidant properties, polyphenolic content and multidrug resistant bacteria
      of Salvia verticcilata L. MATERIALS AND METHODS: Methanol was used as the
      extraction solvent. The total phenolic content was calculated using Folin
      Ciocalteau method and phenolic composition was determined by HPLC. The radical
      scavenging activity of plant was evaluated in vitro based on the reduction of the
      stable DPPH free radical. The reducing capacity was identified by using the FRAP
      method. The ability of Salvia verticcilata L. to increase the permeability of
      multidrug resistant bacterial cells was conducted by flow cytometric assay on
      Listeria innocua and E-coli. RESULTS: The amount of total phenolics was found to
      be 347.5 mg GA/g extract. The IC50 value and FRAP assay are 0.61, and 0.944
      respectively, Free radical scavenging effect and FRAP values are less than
      synthetic antioxidant compounds (BHA and BHT). Eight phenolic compounds were
      found in Salvia verticcilata L. Intense concentration of S. verticcilata L. has
      destroyed 97 % of living cells for Listeria innocua and 94.86% for E-coli.
      CONCLUSION: This study shows that methanolic extracts of Salvia verticcilata L.
      is a potential source of natural antioxidants and antimicrobial agent and can
      form the basis for pharmacological studies.

PMID- 25392596
TI  - Cognitive vulnerability to depression during middle childhood: Stability and
      associations with maternal affective styles and parental depression.
AB  - Theories of cognitive vulnerability to depression (CVD) imply that CVD is early
      emerging and trait-like; however, little longitudinal work has tested this
      premise in middle childhood, or examined theoretically relevant predictors of
      child CVD. We examined test-retest correlations of self-referent encoding task
      performance and self-reported attributional styles and their associations with
      parental characteristics in 205 seven-year-olds. At baseline, child CVD was
      assessed, structured clinical interviews were conducted with parents, and ratings
      of observed maternal affective styles were made. Children's CVD was re-assessed
      approximately one and two years later. Both measures of children's CVD were
      prospectively and concurrently associated with children's depressive symptoms and
      showed modest stability. Multilevel modeling indicated that maternal criticism
      and paternal depression were related to children's CVD. Findings indicate that
      even early-emerging CVD is a valid marker of children's depression risk.

PMID- 25392598
TI  - Enhancing the Cultural Sensitivity of Cognitive Behavioral Interventions for
      Anxiety in Diverse Populations.

PMID- 25392597
TI  - The association between bile salt export pump single-nucleotide polymorphisms and
      primary biliary cirrhosis susceptibility and ursodeoxycholic acid response.
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic and progressive
      cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile
      salt efflux system of hepatocytes. BSEP gene has been attached great importance
      in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA)
      treatment of PBC patients. METHODS: In this study, TaqMan assay was used to
      genotype four variants of BSEP, and the Barcelona criteria were used for
      evaluating the response rate of UDCA treatment. RESULTS: Variant A allele of BSEP
      rs473351 (dominant model, OR = 2.063; 95% CI, 1.254-3.393; P = 0.004) was highly
      associated with PBC susceptibility. On the contrary, variant A allele of BSEP
      rs2287618 (dominant model, OR = 0.617; 95% CI, 0.411-0.928; P = 0.020) provided a
      protective role and Barcelona evaluation criterion indicated that the frequency
      of variant allele at BSEP rs2287618 was significantly decreased in UDCA
      responsive PBC patients (P = 0.021). CONCLUSION: These results suggested that
      BSEP rs473351 was closely associated with the susceptibility of PBC and if people
      with BSEP rs2287618 were diagnosed as PBC, the UDCA treatment was not
      satisfactory. Larger studies with mixed ethnicity subjects and stratified by
      clinical and subclinical characteristics are needed to validate our findings.

PMID- 25392599
TI  - Effects of coarse-graining on the scaling behavior of long-range correlated and
      anti-correlated signals.
AB  - We investigate how various coarse-graining (signal quantization) methods affect
      the scaling properties of long-range power-law correlated and anti-correlated
      signals, quantified by the detrended fluctuation analysis. Specifically, for
      coarse-graining in the magnitude of a signal, we consider (i) the Floor, (ii) the
      Symmetry and (iii) the Centro-Symmetry coarse-graining methods. We find that for
      anti-correlated signals coarse-graining in the magnitude leads to a crossover to
      random behavior at large scales, and that with increasing the width of the coarse
      graining partition interval Delta, this crossover moves to intermediate and small
      scales. In contrast, the scaling of positively correlated signals is less
      affected by the coarse-graining, with no observable changes when Delta < 1, while
      for Delta > 1 a crossover appears at small scales and moves to intermediate and
      large scales with increasing Delta. For very rough coarse-graining (Delta > 3)
      based on the Floor and Symmetry methods, the position of the crossover
      stabilizes, in contrast to the Centro-Symmetry method where the crossover
      continuously moves across scales and leads to a random behavior at all scales;
      thus indicating a much stronger effect of the Centro-Symmetry compared to the
      Floor and the Symmetry method. For coarse-graining in time, where data points are
      averaged in non-overlapping time windows, we find that the scaling for both anti
      correlated and positively correlated signals is practically preserved. The
      results of our simulations are useful for the correct interpretation of the
      correlation and scaling properties of symbolic sequences.

PMID- 25392600
TI  - Antecedents of Physical Activity Among Family Caregivers.
AB  - OBJECTIVES: We examined exercise behaviors among family caregivers and the degree
      to which aspects of the caregiving role influenced exercise behaviors.
      Understanding factors associated with caregiver physical activity provides
      practitioners the means to design and tailor interventions to be effective for
      caregivers. METHODS: Caregivers (N=208) participating in a self-care intervention
      to promote caregiving skills were surveyed at baseline, prior to training.
      Measures included caregiver characteristics, care recipient characteristics,
      attitudes and intentions toward exercise and levels of physical activity.
      RESULTS: Mental health variables and self-efficacy for exercise were
      significantly related to exercise levels in bivariate analyses. Regression
      analyses revealed that caregiver and care recipient characteristics accounted for
      a small percentage of the variance in exercise behavior. DISCUSSION: Caregiver
      vitality and self-efficacy for exercise were key variables most significantly
      related to exercise behaviors. Findings suggest that mental health factors and
      attitudes about exercise may be more important predictors of exercise than
      caregiving factors.

PMID- 25392601
TI  - Ethnic Residential Segregation by Nativity in Great Britain and the United
      States*
AB  - This study examines patterns of ethnic residential integration in Great Britain
      and the United States. Using data from 2000/2001 censuses from these two
      countries, we compute segregation indexes for comparably-defined ethnic groups by
      nativity and for specific foreign-born groups. We find that blacks are much less
      segregated in Great Britain than in the U.S, and black segregation patterns by
      nativity tend to be consistent with spatial assimilation in the former country
      (the foreign born are more segregated than the native born) but not in the
      latter. Among Asian groups, however, segregation tends to be lower in the United
      States, and segregation patterns by nativity are more consistent with spatial
      assimilation in the U.S. but not in Great Britain. These findings suggest that
      intergenerational minority disadvantage persists among blacks in the U.S. and
      among Asians in Great Britain. We caution, however, that there are important
      differences in levels of segregation among specific foreign-born Asian groups,
      suggesting that assimilation trajectories likely differ by country of origin.
      Finally, the fact that segregation levels are considerably higher in the U.S. for
      a majority of groups, including white foreign-born groups, suggests that factors
      not solely related to race or physical appearance drive higher levels of ethnic
      residential segregation in the U.S.

PMID- 25392602
TI  - Neuroscientific Evidence About the Distinction Between Short- and Long-Term
      Memory.
AB  - What have neuroscientific techniques contributed to the development of
      psychological theory about short- and long-term memory? We argue that the
      contributions have been varied: In some cases, data about brain mechanisms have
      been vital to the advancement of psychological theory; in other cases,
      neuroscientific data and behavioral data from normal participants have made equal
      contributions; and in yet other cases, the data from neuroscientific approaches
      have actually led psychological theory astray. We illustrate these various
      contributions by focusing on the relationship of short- to long-term memory.

PMID- 25392603
TI  - SEMI-DEFINITE PROGRAMMING TECHNIQUES FOR STRUCTURED QUADRATIC INVERSE EIGENVALUE
      PROBLEMS.
AB  - In the past decade or so, semi-definite programming (SDP) has emerged as a
      powerful tool capable of handling a remarkably wide range of problems. This
      article describes an innovative application of SDP techniques to quadratic
      inverse eigenvalue problems (QIEPs). The notion of QIEPs is of fundamental
      importance because its ultimate goal of constructing or updating a vibration
      system from some observed or desirable dynamical behaviors while respecting some
      inherent feasibility constraints well suits many engineering applications. Thus
      far, however, QIEPs have remained challenging both theoretically and
      computationally due to the great variations of structural constraints that must
      be addressed. Of notable interest and significance are the uniformity and the
      simplicity in the SDP formulation that solves effectively many otherwise very
      difficult QIEPs.

PMID- 25392604
TI  - On the Origins of Disorganized Attachment and Internal Working Models: Paper I. A
      Dyadic Systems Approach.
AB  - Despite important recent progress in understanding disorganized attachment, we
      still lack a full understanding of the mechanisms of disorganized attachment
      formation and transmission prior to 12 months. In this paper we lay out our
      recommendations for the study of the 4-month origins of disorganized attachment.
      In our subsequent Paper II we report on the results of a large empirical study
      that was conducted along the lines we recommend in Paper I. Both Papers I and II
      are based on Beebe, Jaffe, Markese, Buck, Chen, Cohen, Bahrick, Andrews,
      Feldstein (2010). In Paper I we describe our proposal that a detailed
      microanalysis of 4-month mother-infant face-to-face communication would further
      inform our understanding of the process of disorganized attachment formation
      between mother and infant. Such a microanalysis would allow us to characterize
      the nature of the 4-month infant's procedural representations, or emerging
      "internal working models" of attachment.

PMID- 25392605
TI  - A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of
      Treatment Entry and Completion in Prison.
AB  - The present report is an intent-to-treat analysis involving secondary data drawn
      from the first randomized clinical trial of prison-initiated methadone in the
      United States. This study examined predictors of treatment entry and completion
      in prison. A sample of 211 adult male prerelease inmates with preincarceration
      heroin dependence were randomly assigned to one of three treatment conditions:
      counseling only (counseling in prison; n= 70); counseling plus transfer
      (counseling in prison with transfer to methadone maintenance treatment upon
      release; n= 70); and counseling plus methadone (methadone maintenance in prison,
      continued in a community-based methadone maintenance program upon release; n=
      71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001)
      were significantly predicted by the set of 10 explanatory variables and favored
      the treatment conditions receiving methadone. The present results indicate that
      individuals who are older in age and have longer prison sentences may have better
      outcomes than younger individuals with shorter sentences, meaning they are more
      likely to enter and complete prison-based treatment. Furthermore, implications
      for the treatment of prisoners with prior heroin dependence and for conducting
      clinical trials may indicate the importance of examining individual
      characteristics and the possibility of the examination of patient preference.

PMID- 25392606
TI  - Sexual Experience and Risky Alcohol Consumption among Incoming First-Year College
      Females.
AB  - This study examines the relationship between sexual experience and various
      drinking measures in 550 incoming first-year college females. During this
      transition period, sexually experienced participants reported stronger alcohol
      expectancies and endorsed higher drinking motives, and drank more frequently and
      in greater quantities than sexually inexperienced participants. Sexual status was
      also a significant predictor of alcohol-related nonsexual consequences, over and
      above amount consumed. Furthermore, controlling for drinking, sexual status
      moderated the relationship between coping motives and consequences. Among women
      who endorsed strong coping motives for drinking, sexual experience was linked to
      greater nonsexual alcohol-related consequences. Implications for prevention and
      intervention are discussed.

PMID- 25392607
TI  - Training surgery residents and fellows in the rigorous evaluation of academic
      literature.

PMID- 25392608
TI  - Lymphovascular space invasion in robotic surgery for endometrial cancer.
AB  - BACKGROUND: Minimally invasive surgery has become a standard treatment for
      endometrial cancer and offers significant benefits over abdominal approaches.
      There are discrepant data regarding lymphovascular space invasion (LVSI) and
      positive peritoneal cytology with the use of a uterine manipulator, with previous
      small-scale studies demonstrating an increased incidence of these prognostically
      important events. We sought to determine if there was a higher incidence of LVSI
      in patients who underwent robot-assisted surgery for endometrial cancer. METHODS:
      We performed a single-institution review of medical records for patients who
      underwent open abdominal or robot-assisted hysterectomy for endometrial cancer
      over a 24-month period. The following data were abstracted: age, tumor grade and
      stage, size, depth of invasion, LVSI, and peritoneal cytology. For patients with
      LVSI, slides were reviewed by 2 pathologists for confirmation of LVSI. RESULTS:
      Of 104 patients identified, LVSI was reported in 39 (37.5%) and positive
      peritoneal cytology in 6 (4.8%). Rates of peritoneal cytology were not
      significantly different between the 2 groups (odds ratio, 0.55; 95% confidence
      interval, 0.10-3.17; P=.50). LVSI was reported in significantly fewer robot
      assisted hysterectomies than open procedures (odds ratio, 0.39; 95% confidence
      interval, 0.17-0.92; P=.03). In subgroup analyses restricted to early-stage
      disease (stage<=II), there was no significant difference in LVSI between open and
      robot-assisted hysterectomies (odds ratio, 0.64; 95% confidence interval, 0.22
      1.85; P=.43). CONCLUSION: In this retrospective study, we found that use of a
      uterine manipulator in robot-assisted surgery did not increase the incidence of
      LVSI.

PMID- 25392609
TI  - Secondary hemorrhage after total laparoscopic hysterectomy.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study is to estimate the
      cumulative incidence, patient characteristics, and potential risk factors for
      secondary hemorrhage after total laparoscopic hysterectomy. METHODS: All women
      who underwent total laparoscopic hysterectomy at Paul's Hospital between January
      2004 and April 2012 were included in the study. Patients who had bleeding per
      vaginam between 24 hours and 6 weeks after primary surgery were included in the
      analysis. RESULTS: A total of 1613 patients underwent total laparoscopic
      hysterectomy during the study period, and 21 patients had secondary hemorrhage
      after hysterectomy. The overall cumulative incidence of secondary hemorrhage
      after total laparoscopic hysterectomy was 1.3%. The mean size of the uterus was
      541.4 g in the secondary hemorrhage group and 318.9 g in patients without
      hemorrhage, which was statistically significant. The median time interval between
      hysterectomy and secondary hemorrhage was 13 days. Packing was sufficient to
      control the bleeding in 13 patients, and 6 patients required vault suturing.
      Laparoscopic coagulation of the uterine artery was performed in 1 patient.
      Uterine artery embolization was performed twice in 1 patient to control the
      bleeding. CONCLUSIONS: Our data suggest that secondary hemorrhage is rare but may
      occur more often after total laparoscopic hysterectomy than after other
      hysterectomy approaches. Whether it is related to the application of thermal
      energy to tissues, which causes more tissue necrosis and devascularization than
      sharp culdotomy in abdominal and vaginal hysterectomies, is not clear. A large
      uterus size, excessive use of an energy source for the uterine artery, and
      culdotomy may play a role.

PMID- 25392610
TI  - Risk factors for perioperative anxiety in laparoscopic surgery.
AB  - BACKGROUND AND OBJECTIVES: Our aim is to investigate the anxiety status of the
      patient before elective cholecystectomy and to analyze the relation between the
      level of anxiety for a given operation type (laparoscopic and open
      cholecystectomy) and the corresponding demographic and social data. METHODS: A
      total of 333 patients undergoing cholecystectomy due to cholelithiasis were
      included in the study; 218 patients (66.1%) received laparoscopic cholecystectomy
      and 115 patients (33.9%) were treated with open cholecystectomy. The Beck Anxiety
      Inventory was given to all patients to be completed. We evaluated levels of
      anxiety in 3 groups as follows: 0 to 15, low to mild anxiety; 16 to 25, moderate
      anxiety; 26 to 63, severe anxiety. The following patient information remained
      confidential and was recorded: age and sex, associated disease, civil status,
      educational status, having open/laparoscopic cholecystectomy, previous knowledge
      of the operation, job status, economic status, health insurance, and having a
      child in need of care. RESULTS: The following criteria were determined: the most
      determinant factors in differentiating between the score groups were having a low
      level of education, being of the female sex, being single, and having
      laparoscopic operation; the factors of being a homemaker and over the age of 25
      years were determined to have significant effects. CONCLUSIONS: When analyzing
      the results that may appear during the intraoperative and postoperative period,
      understanding preoperative anxiety, analyzing the risk factors in depth, and
      taking the necessary precautions are all considerations that need to be the
      primary objectives of operators who are involved with laparoscopic, endoscopic,
      and robotic surgery.

PMID- 25392611
TI  - Sealing of vessels larger than 7 millimeters using Enseal in porcine aorta.
AB  - BACKGROUND: The Enseal (Ethicon Endo-Surgery, Blue Ash, Ohio) tissue-sealing
      device has proven efficacy for ligation of vessels<7 mm in diameter, even with
      significant supraphysiologic bursting pressures. We aimed to evaluate the safety
      of Enseal in porcine vessels>7 mm. MATERIALS AND METHODS: The lumbar aortas of
      pigs that were euthanized for unrelated procedures were harvested. A 5- to 6-cm
      segment of aorta was sealed using the Enseal device. The opposite end was
      attached to a pressure-testing device to measure pressures at leak or bursting.
      The bivariate Pearson correlation was used to determine the relationship between
      diameter and bursting pressure. One-way analysis of variance was used to
      determine differences between the groups of vessels on the basis of their
      diameter. RESULTS: Ninety samples of 5-cm aorta segments were used to assess
      bursting pressure. The median diameter was 14 mm (range, 7-18) and bursting
      pressure was 85 mm Hg (range, 24-650). The Pearson test showed a negative
      correlation between vessel diameter and bursting pressure (P=.25). One-way
      analysis of variance did not show any significant difference between vessel
      diameters grouped by size (P=.517), and neither did the Scheffe post hoc test
      when comparing diameter with bursting pressure; 31% of specimens failed to seal.
      CONCLUSIONS: Bursting pressures are low and inconsistent after tissue sealing
      with the Enseal device in porcine vessels>7 mm. These vessels also demonstrated a
      higher rate of failure to seal. The histologic results of the aorta segments (ie,
      a low collagen-elastin ratio) may be the cause of the low bursting pressures.

PMID- 25392612
TI  - Quality of life comparing dor and toupet after heller myotomy for achalasia.
AB  - BACKGROUND: Laparoscopic Heller cardiomyotomy (LHC) is standard therapy for
      achalasia. Traditionally, an antireflux procedure has accompanied the myotomy.
      This study was undertaken to compare quality-of-life outcomes between patients
      undergoing myotomy with Toupet versus Dor fundoplication. In addition, we
      investigated overall patient satisfaction after LHC in the treatment of
      achalasia. METHODS: One hundred thirty-five patients who underwent LHC over a 13
      year period were identified for inclusion. Symptoms queried included dysphagia,
      heartburn, and bloating using the Gastroesophageal Reflux Disease-Health-Related
      Quality of Life Scale and a second published scale for the assessment of
      gastroesophageal reflux disease and dysphagia symptoms. The patients' overall
      satisfaction after surgery was also rated. Data were compared on the basis of
      type of fundoplication. Symptom scores were analyzed using chi-square tests and
      Fisher's exact tests. RESULTS: Sixty-three patients completed the survey (47%).
      There were no perioperative deaths or reoperations. The mean length of stay was
      2.8 days. The mean operative time for LHC with Toupet fundoplication was 137.3+/
      30.91 minutes and for LHC with Dor fundoplication was 111.5+/-32.44 minutes
      (P=.006). There was no difference with respect to the incidence or severity of
      postoperative heartburn, dysphagia, or bloating. Overall satisfaction with Toupet
      fundoplication was 87.5% and with Dor fundoplication was 93.8% (P>.999).
      CONCLUSIONS: LHC with either Toupet or Dor fundoplication gave excellent patient
      satisfaction. Postoperative symptoms of heartburn and dysphagia were equivalent
      when comparing LHC with either antireflux procedure. Dor and Toupet
      fundoplication were found to have equivalent outcomes in the short term. We
      prefer Dor to Toupet fundoplication because of its decreased need for extensive
      dissection and better mucosal protection.

PMID- 25392613
TI  - Single-site Nissen fundoplication versus laparoscopic Nissen fundoplication.
AB  - BACKGROUND: Advances in minimally invasive surgery have led to the emergence of
      single-incision laparoscopic surgery (SILS). The purpose of this study is to
      assess the feasibility of SILS Nissen fundoplication and compare its outcomes
      with traditional laparoscopic Nissen fundoplication. METHODS: This is a
      retrospective study of 33 patients who underwent Nissen fundoplication between
      January 2009 and September 2010. RESULTS: There were 15 SILS and 18 traditional
      laparoscopic Nissen fundoplication procedures performed. The mean operative time
      was 129 and 182 minutes in the traditional laparoscopic and single-incision
      groups, respectively (P=.019). There were no conversions in the traditional
      laparoscopic group, whereas 6 of the 15 patients in the SILS group required
      conversion by insertion of 2 to 4 additional ports (P=.0004). At short-term
      follow-up, recurrence rates were similar between both groups. To date, there have
      been no reoperations. CONCLUSIONS: SILS Nissen fundoplication is both safe and
      feasible. Short-term outcomes are comparable with standard laparoscopic Nissen
      fundoplication. Challenges related to the single-incision Nissen fundoplication
      include overcoming the lengthy learning curve and decreasing the need for
      additional trocars.

PMID- 25392614
TI  - Laparoscopic ablative and reconstructive surgeries in genitourinary tuberculosis.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopy is the present standard of care for
      urologic diseases. Laparoscopy in renal tuberculosis (genitourinary tuberculosis)
      is difficult because of inflammation and fibrosis associated with the disease. We
      present the outcome of our experience of laparoscopy in genitourinary
      tuberculosis, both ablative and reconstructive. METHODS: The detailed data of
      patients with genitourinary tuberculosis who underwent laparoscopic surgeries
      between January 2011 and September 2012 were reviewed. Indications, type of
      surgery, duration, blood loss, intraoperative problems, postoperative outcomes,
      and follow-up details were noted. RESULTS: Overall, 7 laparoscopic procedures
      were performed: 5 nephrectomies, 1 ureteric reimplantation with psoas hitch, and
      1 combined nephrectomy and laparoscopy-assisted Mainz II pouch reconstruction.
      The mean operative time was 192 minutes for nephrectomy, 210 minutes for ureteric
      reimplantation, and 480 minutes for nephrectomy with Mainz II pouch
      reconstruction. There were no conversions to open surgery. The mean amount of
      blood loss was 70 mL for the nephrectomies, 100 mL for ureteric reimplantation,
      and 200 mL for nephrectomy with Mainz II pouch reconstruction. In 5 of 6 patients
      who underwent nephrectomy, there was severe perinephric and peripelvic fibrosis
      posing difficulty in dissection. However, the renal vessels could be controlled
      individually. The mean postoperative hospital stay was 3 days for the
      nephrectomies, 5 days for the ureteric reimplantation, and 10 days for the
      nephrectomy with Mainz II pouch reconstruction. In all cases the recovery was
      uneventful. CONCLUSIONS: Laparoscopy, though technically more demanding, is a
      feasible and safe option for ablative and complex reconstructive procedures in
      genitourinary tuberculosis. It offers the benefits of minimally invasive surgery.
      The difficulty with this procedure is mostly because of peripelvic and
      perinephric fibrosis, whereas the lower ureter and bladder are relatively easier
      to dissect.

PMID- 25392615
TI  - Modified retroperitoneoscopic port sites for surgery of upper urinary tract.
AB  - BACKGROUND AND OBJECTIVES: Our objective was to introduce our experience using
      modified retroperitoneoscopic port positions for operations of the upper urinary
      tract. METHODS: We designed different trocar positions or incisions according to
      different surgical procedures and specimen sizes. A total of 116 patients,
      comprising patients with common adrenal, kidney, and ureter diseases, underwent
      retroperitoneoscopic operations by use of modified incisions. These patients
      comprised 23 with adrenal diseases, 84 with kidney diseases, and 9 with ureter
      diseases. The specimen was retrieved, as much as possible, through a transverse
      incision to produce a hidden scar after recovery. By contrast, 143 patients
      underwent the same or similar procedures using classical 3-port incisions. The
      operative time was defined as the time from skin incision to skin closure.
      RESULTS: There were no significant differences in age, estimated blood loss, oral
      intake, and hospital stay between groups. A significant difference in favor of
      the modified group was noted with respect to analgesia use (diclofenac sodium, 50
      mg vs 100 mg; P<.05) in all 3 modified methods, as well as in cosmetic outcome in
      the groups undergoing the first modification (score, 8.9+/-2.2 VS 7.3+/-2.8;
      P<.05) and second modification (score, 8.7+/-2.5 VS 7.1+/-2.4; P<.05). In
      addition, the mean operative time in patients undergoing ureter operations was
      shorter than that in the conventional group using classical 3-port positions
      (55+/-11 minutes vs 70+/-15 minutes, P<.05). CONCLUSIONS: Our modified
      retroperitoneoscopic incision is a safe, cosmetic alternative procedure for
      operations of the upper urinary tract. Different diseases and specimen sizes can
      be treated with the personalized or suitable incisions that we have introduced.

PMID- 25392616
TI  - Laparoendoscopic single-site herniorrhaphy after gynecologic surgery.
AB  - BACKGROUND AND OBJECTIVES: Increased interest in laparoendoscopic single-site
      surgery has instigated research into trials of novel techniques. The procedure we
      propose may potentially improve patient satisfaction and cosmetic results while
      diminishing the incidence of trocar-site herniation. We report our initial
      experience with laparoendoscopic single-site totally extraperitoneal
      herniorrhaphy for postoperative incisional hernia to determine the procedure's
      feasibility and safety. METHODS: Three patients with incisional hernias after
      gynecologic surgery underwent laparoendoscopic single-site totally
      extraperitoneal procedures. We evaluated the patients' preoperative and
      postoperative condition, as well as the details of their original surgery. We
      performed the procedure through a 2-cm umbilical incision followed by mesh
      insertion and transabdominal suture placement in all patients. RESULTS:
      Laparoendoscopic single-site totally extraperitoneal herniorrhaphy was completed
      in 80 to 120 minutes. No intraoperative complications were encountered, and
      surgical blood loss was minimal. The duration of hospital stay ranged from 2 to 4
      days. One patient had a postoperative wound infection. The patients have shown no
      sign of recurrence at 9 months' follow-up. CONCLUSION: Laparoendoscopic single
      site totally extraperitoneal herniorrhaphy appears to be feasible and safe. It
      may be performed with readily available instruments, although further experience
      and practice are warranted for a more efficient repair. The procedure has similar
      advantages to a multiport laparoscopic totally extraperitoneal procedure but
      yields better cosmetic results. More studies are needed to assess the long-term
      benefits and complications of this procedure.

PMID- 25392617
TI  - Criteria for selection of laparoscopy for women with adnexal mass.
AB  - OBJECTIVES: We compared the indication of laparoscopy for treatment of adnexal
      masses based on the risk scores and tumor diameters with the indication based on
      gynecology-oncologists' experience. METHODS: This was a prospective study of 174
      women who underwent surgery for adnexal tumors (116 laparotomies, 58
      laparoscopies). The surgeries begun and completed by laparoscopy, with benign
      pathologic diagnosis, were considered successful. Laparoscopic surgeries that
      required conversion to laparotomy, led to a malignant diagnosis, or facilitated
      cyst rupture were considered failures. Two groups were defined for laparoscopy
      indication: (1) absence of American College of Obstetrics and Gynecology (ACOG)
      guideline for referral of high-risk adnexal masses criteria (ACOG negative)
      associated with 3 different tumor sizes (10, 12, and 14 cm); and (2) Index of
      Risk of Malignancy (IRM) with cutoffs at 100, 200, and 300, associated with the
      same 3 tumor sizes. Both groups were compared with the indication based on the
      surgeon's experience to verify whether the selection based on strict rules would
      improve the rate of successful laparoscopy. RESULTS: ACOG-negative and tumors<=10
      cm and IRM with a cutoff at 300 points and tumors<=10 cm resulted in the same
      best performance (78% success=38/49 laparoscopies). However, compared with the
      results of the gynecology-oncologists' experience, those were not statistically
      significant. DISCUSSION: The selection of patients with adnexal mass to
      laparoscopy by the use of the ACOG guideline or IRM associated with tumor
      diameter had similar performance as the experience of gynecology-oncologists.
      Both methods are reproducible and easy to apply to all women with adnexal masses
      and could be used by general gynecologists to select women for laparoscopic
      surgery; however, referral to a gynecology-oncologist is advisable when there is
      any doubt.

PMID- 25392618
TI  - Comparing the da Vinci si single console and dual console in teaching novice
      surgeons suturing techniques.
AB  - BACKGROUND AND OBJECTIVES: Robot-assisted laparoscopic surgery is often taught
      with the surgical mentor at the surgeon console and the trainee at the patient's
      bedside. The da Vinci dual console (Intuitive Surgical, Sunnyvale, California)
      allows a surgical mentor to teach with both the mentor and the trainee working at
      a surgeon console simultaneously. The purpose of this study is to evaluate the
      effectiveness of the dual console versus the single console for teaching medical
      students robotic tasks. METHODS: Forty novice medical students were randomized to
      either the da Vinci single-console or dual-console group and were taught 4 knot
      tying techniques by a surgical mentor. The students were timed while performing
      the tasks. RESULTS: No statistically significant differences in mean task times
      were observed between the single- and dual-console groups: interrupted stitch
      with a 2-handed knot (300 seconds for single vs 294 seconds for dual, P=.59),
      interrupted stitch with a 1-handed knot (198 seconds for single vs 212 seconds
      for dual, P=.88), figure-of-8 stitch with a 2-handed knot (261 seconds for single
      vs 219 seconds for dual, P=.20), and figure-of-8 stitch with a 1-handed knot (200
      seconds for single vs 199 seconds for dual, P=.53). CONCLUSION: No significant
      difference was observed in performance time when teaching knot-tying techniques
      to medical students using the da Vinci dual console compared with the single
      console. More research needs to be performed on the utility of the da Vinci dual
      console in surgical training.

PMID- 25392619
TI  - Surgical therapy of ovarian endometrioma: recurrence and pregnancy rates.
AB  - BACKGROUND AND OBJECTIVES: The study was designed to analyze preoperative
      clinical and surgical findings at enucleation of ovarian endometrioma with their
      impact on recurrence and pregnancy rates. METHODS: This is a retrospective study
      of 550 histologically verified ovarian endometriomas operated on at the
      Department of Obstetrics and Gynecology, University Hospital Kiel, Germany,
      between 1995 and 2004. Preoperative data, surgical findings, and postoperative
      outcomes of 289 cases were analyzed. The average follow-up period was 12.9 years.
      RESULTS: Ovarian endometriomas recurred in 23.9% of patients. Risk factors
      identified for recurrence of endometriomas were preoperative pain (P=.013),
      dysmenorrhea (P=.013), larger cyst size (>8 cm), younger age (<25 years), and
      preoperative cyst rupture. Factors associated with postoperative dysmenorrhea
      were younger age<25 years (P<.001), nulliparity (P=.020), and lager cyst size>8
      cm (P=.048). Recurrence of pain was influenced by previous surgery of
      endometrioma (P<.05). Laparoscopy had a higher percentage of symptom-free
      patients than laparotomy did (49.0% vs 33.3%). Additional postoperative hormonal
      treatment resulted in a higher spontaneous pregnancy rate (41.4% vs 12.6%;
      P<.001) but a lower recurrence-free interval rate (70.5% vs 82.6%; P=.050) when
      compared with surgery only. CONCLUSIONS: We identified preoperative and
      intraoperative findings associated with higher risk of recurrence of
      endometrioma, pain, and dysmenorrhea. Patients desiring pregnancy benefited from
      postoperative hormone treatment, but no favorable results from combined therapy
      were observed with regard to recurrence rate.

PMID- 25392620
TI  - Minimally invasive hysterectomy at a university teaching hospital.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the feasibility of a minimally invasive
      approach for hysterectomy for benign disease at a university teaching hospital.
      METHODS: Five hundred thirty-seven consecutive patients underwent hysterectomy
      for benign disease at Penn State Milton S. Hershey Medical Center in 2010. No
      cases were excluded. Minimally invasive approaches included total vaginal
      hysterectomy, laparoscopy-assisted vaginal hysterectomy, total laparoscopic
      hysterectomy, and laparoscopic supracervical hysterectomy. All surgeries were
      completed with the resident as the primary surgeon or first assistant. RESULTS:
      The median age was 45 years, the median body mass index was 30 kg/m2, the median
      estimated uterine size was 11 cm, and 22% of patients had a prior cesarean
      section. Of the 537 hysterectomies, 526 (98%) were started with a minimally
      invasive approach and 517 (96%) were completed in that fashion; thus only 9
      conversions (2%) were required. Of the cases in which a minimally invasive
      approach was used, 16% were vaginal and 84% were laparoscopic. The median
      operative time was 86 minutes, the median blood loss was 95 mL, the median
      hospital stay was 1 day, and the median uterine weight was 199 g. For the
      minimally invasive hysterectomies, there was a 5% major complication rate.
      CONCLUSION: Our residency training institution completed 96% of 537
      hysterectomies using a minimally invasive approach while maintaining an
      acceptable operative time, amount of blood loss, hospital stay, and complication
      rate. Thus our study supports that a minimally invasive approach for hysterectomy
      for benign disease at an academic resident teaching facility is feasible.

PMID- 25392621
TI  - Laparoscopy-assisted supracervical hysterectomy for ovarian cancer: cervical
      recurrence.
AB  - BACKGROUND AND OBJECTIVES: The purpose of our study is to evaluate the incidence
      of cervical recurrence after laparoscopic supracervical hysterectomy for ovarian
      cancer debulking or staging. METHODS: From a prospective surgical database, we
      identified 51 cases of laparoscopic supracervical hysterectomy for ovarian cancer
      debulking or staging. No cases were excluded. RESULTS: From 2009 to 2012, 51
      patients were identified. The median age was 62 years (range, 32-83 years), and
      the median body mass index was 29 kg/m2 (range, 16-41 kg/m2). Medical
      comorbidities were present in 40 patients (78%), and 53% had prior abdominal
      surgery. The median operative time was 2 hours (range, 1-3.5 hours), and the
      median blood loss was 200 mL (range, 50-900 mL). The median length of stay was 1
      day (range, 0-12 days). The stage was I in 12 patients, II in 6, and III/IV in
      33. At a median follow-up time of 1.7 years (range, 0.3-2.6 years), 20 patients
      (39%) had recurrence of cancer, with a median time of recurrence of 1.1 years
      (range, 0.3-2.3 years). All recurrences were in the abdomen or pelvis except for
      1 axillary node recurrence and 1 recurrence in the distal vagina. There were no
      recurrences in the remaining cervical stump. No patient had a postoperative
      vaginal cuff infection. Among the 104 cycles of intraperitoneal chemotherapy,
      there was no vaginal leakage of intraperitoneal chemotherapy. CONCLUSION:
      Laparoscopic supracervical hysterectomy for ovarian cancer debulking or staging
      does not result in cervical recurrence.

PMID- 25392622
TI  - Adoption of robotic sacrocolpopexy at an academic institution.
AB  - OBJECTIVES: To describe the introduction of robotic sacrocolpopexy (RSC) in a
      urogynecology fellowship program, including operative times and patient outcomes.
      METHODS: Data were retrospectively extracted from all women who underwent RSC
      between May 1, 2009 and December 31, 2011 by a single urogynecologist with fellow
      and resident assistance. Patient demographics, operative times, intraoperative
      complications, length of hospital stay, and postoperative course were analyzed.
      Cases were grouped chronologically in blocks of 10 for analysis. Trend analysis
      of operative time was done with linear and negative binomial regression. Fisher's
      exact test was used to compare complications among blocks. RESULTS: Fifty-two
      patients (mean age 58.5+/-8.4 years) underwent RSC. The majority (75%) had stage
      III prolapse. Forty-one patients (79%) had concomitant procedures, including
      supracervical hysterectomy (44%), bilateral salpingo-oophorectomy (9.6%),
      midurethral sling (9.6%), and lysis of adhesions (40.4%). There was no trend
      toward decreased operative time with increased surgical experience (linear
      regression P=.453, negative binomial regression P=.998). Mean operative time was
      301.1+/-53.1 minutes (range 205-440). Overall complication rate was not
      associated with number of robotic cases performed (P=.771). Nine cases (17.3%)
      were converted to laparotomy. Five of these occurred in the first 15 cases. There
      were 2 bladder injuries (3.8%) and no bowel injuries. CONCLUSIONS: Although a
      learning curve was not demonstrated, the adoption of RSC into a urogynecology
      fellowship program yields similar rates of bladder/bowel injuries, postoperative
      complications, and operative times when compared with other published studies.

PMID- 25392623
TI  - Laparoscopic adjustable gastric band: how to reduce the early morbidity.
AB  - BACKGROUND: Laparoscopic adjustable gastric band insertion is a safe weight
      reduction procedure, but serious complications can develop. The aim of this study
      was to evaluate our technique in preventing early band complications. METHODS:
      Patients were given the choice of procedure according to body mass index, the
      presence of diabetes, and preference. Weight loss data were not considered, as
      our aim was to evaluate the morbidity of band surgery using a specific technique.
      A pars flaccida approach and plication technique were used for all patients.
      Postoperative follow-up was provided at 1 month, 2 months, and every 3 months for
      the first year and then yearly for a further 2 years. Thereafter, general
      practitioners referred patients if late complications arose. RESULTS: From
      January 2007 to August 2011, 1149 patients (245 men [21.32%], 904 women [78.67%])
      underwent laparoscopic adjustable gastric band insertion under the care of a
      single bariatric surgeon. Patients were hospitalized for 1 night only unless they
      developed early complications. The primary and secondary outcomes were major and
      minor band complications, respectively. Patients' age range was 18 to 64 years
      (mean, 44 years). Body mass index ranged from 33 to 62 kg/m2 (mean, 42 kg/m2).
      There were 2 band erosions (0.17%), 6 cases of band prolapse (0.52%), 4 port
      problems (0.34%), 1 band leak (0.08%), 3 tight bands (0.26%), 2 port infections
      (0.17%), and no deaths. Five procedures (0.43%) were abandoned and excluded from
      this study, and 1 (0.17%) was converted to minilaparotomy to control abdominal
      wall bleeding. The duration of follow-up ranged from 16 to 60 months.
      CONCLUSIONS: A combined pars flaccida and plication technique is associated with
      a low early complication rate.

PMID- 25392624
TI  - Massive splenomegaly in children: laparoscopic versus open splenectomy.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic splenectomy for massive splenomegaly is
      still a controversial procedure as compared with open splenectomy. We aimed to
      compare the feasibility of laparoscopic splenectomy versus open splenectomy for
      massive splenomegaly from different surgical aspects in children. METHODS: The
      data of children aged <12 years with massive splenomegaly who underwent
      splenectomy for hematologic disorders were retrospectively reviewed in 2
      pediatric surgery centers from June 2004 until July 2012. RESULTS: The study
      included 32 patients, 12 who underwent laparoscopic splenectomy versus 20 who
      underwent open splenectomy. The mean ages were 8.5 years and 8 years in the
      laparoscopic splenectomy group and open splenectomy group, respectively. The mean
      operative time was 180 minutes for laparoscopic splenectomy and 120 minutes for
      open splenectomy. The conversion rate was 8%. The mean amount of intraoperative
      blood loss was 60 mL in the laparoscopic splenectomy group versus 110 mL in the
      open splenectomy group. Postoperative atelectasis developed in 2 cases in the
      open splenectomy group (10%) and 1 case in the laparoscopic splenectomy group
      (8%). Oral feeding postoperatively resumed at a mean of 7.5 hours in the
      laparoscopic splenectomy group versus 30 hours in the open splenectomy group. The
      mean hospital stay was 36 hours in the laparoscopic splenectomy group versus 96
      hours in the open splenectomy group. Postoperative pain was less in the
      laparoscopic splenectomy group. CONCLUSION: Laparoscopic splenectomy for massive
      splenomegaly in children is safe and feasible. Although the operative time was
      significantly greater in the laparoscopic splenectomy group, laparoscopic
      splenectomy was associated with statistically significantly less pain, less blood
      loss, better recovery, and shorter hospital stay. Laparoscopic splenectomy for
      pediatric hematologic disorders should be the gold-standard approach regardless
      of the size of the spleen.

PMID- 25392625
TI  - Laparoscopic varicocelectomy: virtual reality training and learning curve.
AB  - OBJECTIVES: To explore the role that virtual reality training might play in the
      learning curve of laparoscopic varicocelectomy. METHODS: A total of 1326
      laparoscopic varicocelectomy cases performed by 16 participants from July 2005 to
      June 2012 were retrospectively analyzed. The participants were divided into 2
      groups: group A was trained by laparoscopic trainer boxes; group B was trained by
      a virtual reality training course preoperatively. The operation time curves were
      drafted, and the learning, improving, and platform stages were divided and
      statistically confirmed. The operation time and number of cases in the learning
      and improving stages of both groups were compared. Testicular artery sparing
      failure and postoperative hydroceles rate were statistically analyzed for the
      confirmation of the learning curve. RESULTS: The learning curve of laparoscopic
      varicocelectomy was 15 cases, and with 14 cases more, it came into the platform
      stage. The number of cases for the learning stages of both groups showed no
      statistical difference (P=.49), but the operation time of group B for the
      learning stage was less than that of group A (P<.00001). The number of cases of
      group B for the improving stage was significantly less than that of group A
      (P=.005), but the operation time of both groups in the improving stage showed no
      difference (P=.30). The difference of testicular artery sparing failure rates
      among these 3 stages was proved significant (P<.0001), the postoperative
      hydroceles rate showed no statistical difference (P=.60). CONCLUSIONS: The
      virtual reality training shortened the operation time in the learning stage and
      hastened the trainees' steps in the improving stage, but did not shorten the
      learning curve as expected to.

PMID- 25392626
TI  - Routine cystoscopy after robotic gynecologic oncology surgery.
AB  - BACKGROUND AND OBJECTIVES: Our aim was to determine whether the use of routine
      cystoscopy increases lower urinary tract injury detection (bladder and/or ureter)
      after robotic surgery performed by gynecologic oncologists. METHODS: A
      retrospective chart review of patients who presented for robotic hysterectomy
      from 2009-2012 was performed at 2 separate academic medical centers, one that
      performed routine cystoscopy and one that did not. Statistical analysis was
      performed with t tests and chi2 tests. RESULTS: We identified 140 cases without
      cystoscopy and 109 cases with routine cystoscopy. There were no intraoperative or
      postoperative urinary injuries detected in either group. There were no
      significant differences in age and body mass index. In the non-cystoscopy group,
      a larger specimen size (P<.001), less blood loss (P=.013), and a longer mean
      operative time were observed (P<.0001). In the routine cystoscopy group, more
      lymphadenectomies were performed with hysterectomy (P=.007) and more patients
      underwent hysterectomy for ovarian cancer (P=.0192). There were no differences in
      surgical indications or secondary procedures including bilateral salpingo
      oophorectomy, radical hysterectomy, ureterolysis, and pelvic organ prolapse
      related procedures. The minimum follow-up period was 30 days in both groups.
      CONCLUSION: Routine use of cystoscopy did not appear to affect the detection rate
      of intraoperative lower urinary tract injury during robotic gynecologic surgery
      because this rate was zero in both groups. However, cystoscopy is relatively
      simple to perform and can be efficiently incorporated into robotic surgery to
      avoid the severe morbidity and possible litigation surrounding a urinary tract
      injury.

PMID- 25392627
TI  - Single-site robotic cholecystectomy.
AB  - BACKGROUND: Laparoscopic single-incision surgery is fraught with significant
      technical drawbacks but has witnessed increased growth mainly for its presumed
      aesthetic advantages. Recently, a single-site robotic platform has been
      introduced to alleviate some of the technical challenges with laparoscopic single
      site surgery, although literature on this topic is scant. The aim of this study
      is to analyze the experience of a single surgeon with single-site robotic
      cholecystectomies since the U.S. Food and Drug Administration gave its approval
      in December 2011, and to evaluate the robotic platform's safety and short-term
      surgical outcomes. METHODS: From February 1st 2012 to February 28th 2013,
      patients who underwent single-site cholecystectomy at an academic institution in
      the United States were retrospectively reviewed from a prospectively maintained
      database. The following variables were analyzed: age, sex, body mass index,
      previous surgeries, total operative time, port insertion time, docking time,
      console time, estimated blood loss, closure time, conversion to open or multiport
      approach, postoperative outcomes for wound infection, bile leak, biliary ductal
      injury, right hepatic artery injury, reoperations, readmission, and mortality.
      Indication for cholecystectomy was symptomatic gallbladder disease. No exclusion
      criteria were used and no cost analysis was performed. RESULTS: During the study
      period, 31 patients were enrolled. The mean patient age, body mass index, weight,
      and operative time was 33.6 years, 32.2 kg/m2, 86.3 kg, and 81.4 minutes,
      respectively. There were no conversions to the open or traditional multiport
      approach, and no major complications of biliary ductal or hepatic artery injury,
      bile leak, reoperations, or mortality occurred. There was 1 case of superficial
      wound infection. CONCLUSIONS: Single-site robotic cholecystectomy is feasible and
      safe and requires a minimal learning curve to transition from traditional
      multiport to single-port robotic cholecystectomy.

PMID- 25392628
TI  - Development of a measurement system for laparoendoscopic single-site surgery:
      reliability and repeatability of digital image correlation for measurement of
      surface deformations in SILS port.
AB  - OBJECTIVE: Analysis of mechanical measurements in laparoendoscopic single-site
      surgery (LESS) is important for instrument design and surgical simulators. The
      aim of this study was to develop a measuring system for different instruments and
      manipulations in LESS using a single-incision laparoscopic surgery (SILS) port.
      METHODS: The loads on the SILS port were applied and recorded by the universal
      material testing machine by the following method. The handle of the forceps
      inserted in the SILS port was connected with the machine by a fishing wire and
      pulled at a constant rate. The surface deformations (displacements and strains)
      of the SILS port were recorded with digital image correlation (DIC)
      simultaneously. The correlation between deformation measurements and loads were
      analyzed. This experiment was repeated 8 times. RESULTS: Strong correlations
      existed between deformation measurements calculated by DIC and objective criteria
      "loads" applied and recorded by the universal material testing machine (r>0.98).
      The correlation coefficients were statistically significant (P<.001). A high
      repeatability of the results appeared in all repetitions of the experiment.
      CONCLUSIONS: A DIC measurement system has been developed for LESS, and
      comprehensive mechanical parameters of a SILS port can be obtained precisely by
      using this system. It is reliable and repeatable for evaluation of instruments
      and manipulations in LESS.

PMID- 25392629
TI  - Endourological treatment of foreign bodies in the urinary system.
AB  - BACKGROUND AND OBJECTIVES: In this retrospective study, nature, clinical
      presentations, diagnostic modalities, and endoscopic treatment of urinary system
      foreign bodies were evaluated. METHODS: A total of 8 cases were treated with
      endoscopic surgery between February 15, 2007 and June 12, 2012. Clinical
      findings, radiologic diagnosis, and management were reviewed. RESULTS: We
      observed that urinary tract foreign bodies were generally secondary to iatrogenic
      causes; however, bladder/urethral foreign bodies could also be due to self
      insertion. Clinical findings were different secondary to their location in the
      urinary system. All foreign bodies were treated endoscopically. CONCLUSIONS:
      Foreign bodies of the urinary system can successfully be treated with endoscopic
      modalities without any complications.

PMID- 25392630
TI  - Laparoscopic transperitoneal left adrenalectomy and wandering spleen risk.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic transperitoneal left adrenalectomy (LTLA)
      has become the standard treatment for adrenal masses<6 cm. LTLA involves the
      dissection of splenic suspensory ligaments, which replicates their congenital
      absence or weakening, present in cases of wandering spleen (WS). WS is a rare
      condition in which the spleen migrates from the left upper quadrant to a more
      caudal location in the abdomen. A unique case of WS after LTLA was described by
      Corcione et al. In this prospective study, we investigated the possibility of WS
      as a consequence of LTLA. METHODS: Twenty-four patients, 8 men and 16 women, who
      underwent LTLA with the dissection of splenoparietal and splenorenal ligaments
      were selected. RESULTS: Clinical and ultrasonographic follow-up showed no
      evidence of postoperative WS. CONCLUSIONS: In the literature, WS is not commonly
      reported as a postoperative complication of LTLA. In effect, especially in the
      case of small adrenal masses, the spleen's repositioning in its seat is
      autonomous. However, the alarming possibility of WS should not be ignored,
      especially in the case of extensive dissection of the left colic flexure. It
      would be useful for other authors to signal this complication, so that different
      approaches and consequent results may be compared.

PMID- 25392631
TI  - Advanced gynecologic laparoscopy in a fast-track ambulatory surgery center.
AB  - BACKGROUND/OBJECTIVES: It has been shown that major gynecologic laparoscopy is
      safe in hospital ambulatory settings, but there is little data to suggest the
      same in freestanding ambulatory surgery centers. This study evaluates the safety
      and efficacy of advanced gynecologic laparoscopic surgery using a fast-track
      model in freestanding ambulatory surgery centers and discusses our institution
      protocols. METHODS: Retrospective, multicenter review was conducted of major
      gynecologic surgeries from August 1st 2010 to September 30th 2011 in 3 surgical
      centers with one primary surgeon. All patients were treated for symptomatic
      uterine leiomyomas and/or endometriosis. Primary outcome measures were unplanned
      admissions and discharge within 23 hours. RESULTS: One hundred and thirty-four
      patients underwent major laparoscopic gynecologic surgery with a total of 160
      procedures: 77 stage IV endometriosis treatment including 7 disk excisions of
      endometriosis from the large bowel, 3 ureteroneocystostomies and 1 partial
      bladder resection, 38 myomectomies, and 34 hysterectomies including 12 modified
      radical hysterectomies. The overall unplanned admission rate was 4.5%. One
      hundred and thirty-one patients (97.7%) were discharged within 24 hours after
      surgery. Three patients (2.2%) were transferred to the hospital postoperatively:
      1 patient for observation of postoperative anemia and 2 patients for
      postoperative fever. Three patients (2.2%) were admitted to the hospital after
      discharge: 1 patient for postoperative ileus, 1 patient for postoperative fever,
      and 1 patient with septic pelvic thrombophlebitis. These postoperative issues all
      resolved without complication, and all patients had an uneventful follow-up.
      CONCLUSIONS: With appropriate resources and an experienced surgeon, advanced
      laparoscopic surgery can be safely performed in a fast-track ambulatory surgery
      center with a high rate of discharge within 23 hours and low unplanned
      readmission rate.

PMID- 25392632
TI  - Needs assessment for electrosurgery training of residents and faculty in
      obstetrics and gynecology.
AB  - BACKGROUND AND OBJECTIVES: Effective application of electrosurgical techniques
      requires knowledge of energy sources and electric circuits to produce desired
      tissue effects. A lack of electrosurgery knowledge may negatively affect patient
      outcomes and safety. Our objective was to survey obstetrics-gynecology trainees
      and faculty to assess their basic knowledge of electrosurgery concepts as a needs
      assessment for formal electrosurgery training. METHODS: We performed an
      observational study with a sample of convenience at 2 academic hospitals (Beth
      Israel Deaconess Medical Center and Mount Auburn Hospital). Grand rounds
      dedicated to electrosurgery teaching were conducted at each department of
      obstetrics and gynecology, where a short electrosurgery multiple-choice
      examination was administered to attendees. RESULTS: The face validity of the test
      content was obtained from a gynecologic electrosurgery specialist. Forty-four
      individuals completed the examination. Test scores were analyzed by level of
      training to investigate whether scores positively correlated with more advanced
      career stages. The median test score was 45.5% among all participants
      (interquartile range, 36.4%-54.5%). Senior residents scored the highest (median
      score, 54.5%), followed by attendings (median score, 45.5%), junior residents and
      fellows (median score in both groups, 36.4%), and medical students (median score,
      27.3%). CONCLUSION: Although surgeons have used electrosurgery for nearly a
      century, it remains poorly understood by most obstetrician-gynecologists. Senior
      residents, attendings, junior residents, and medical students all show a general
      deficiency in electrosurgery comprehension. This study suggests that there is a
      need for formal electrosurgery training. A standardized electrosurgery curriculum
      with a workshop component demonstrating clinically useful concepts essential for
      safe surgical practice is advised.

PMID- 25392633
TI  - Bilateral laparoscopic totally extraperitoneal repair without mesh fixation.
AB  - BACKGROUND AND OBJECTIVES: Mesh fixation during laparoscopic totally
      extraperitoneal repair is thought to be necessary to prevent recurrence. However,
      mesh fixation may increase postoperative chronic pain. This study aimed to
      describe the experience of a single surgeon at our institution performing this
      operation. METHODS: We performed a retrospective review of the medical records of
      all patients who underwent bilateral laparoscopic totally extraperitoneal repair
      without mesh fixation for inguinal hernia from January 2005 to December 2011.
      Demographic, operative, and postoperative data were obtained for analysis.
      RESULTS: A total of 343 patients underwent simultaneous bilateral laparoscopic
      totally extraperitoneal repair of 686 primary and recurrent inguinal hernias from
      January 2005 to December 2011. The mean operative time was 33 minutes. One
      patient was converted to an open approach (0.3%), and 1 patient had
      intraoperative bladder injury. Postoperative hematoma/seroma occurred in 5
      patients (1.5%), wound infection in 1 (0.3%), hematuria in 2 (0.6%), and acute
      myocardial infarction in 1 (0.3%). Chronic pain developed postoperatively in 9
      patients (2.6%); 3 of them underwent re-exploration. All patients were discharged
      home a few hours after surgery except for 3 patients. Among the 686 hernia
      repairs, there were a total of 20 recurrences (2.9%) in 18 patients (5.2%). Two
      patients had bilateral recurrences, whereas 16 had unilateral recurrences. Twelve
      of the recurrences occurred after 1 year (60%). Fourteen recurrences occurred
      among direct hernias (70%). CONCLUSION: Compared with the literature, our
      patients had fewer intraoperative and postoperative complications, less chronic
      pain, and no increase in operative time or length of hospital stay but had a
      slight increase in recurrence rate.

PMID- 25392634
TI  - Laparoscopic varicocelectomy in the management of chronic scrotal pain.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the usefulness of laparoscopic
      varicocelectomy in the management of chronic scrotal pain. METHODS: Between 2009
      and 2011, 48 patients in total were treated with laparoscopic varicocelectomy for
      dull scrotal pain that worsened with physical activity and was attributed to
      varicoceles. All patients were followed up at 3 and 6 months and biannually
      thereafter with a physical examination, visual analog scale score, and
      ultrasonographic scan in selected cases. RESULTS: The mean age was 38.2 years
      (range, 23-54 years). The mean follow-up period was 19.6 months (range, 6-26
      months). Bilateral varicoceles were present in 7 patients (14.6%), and a
      unilateral varicocele was present in 41 (85.4%). The varicocele was grade 3 in 27
      patients (56.3%), grade 2 in 20 (41.6%), and grade 1 in 1 (2.1%). The mean
      preoperative visual analog scale score was 4.8 on a scale from 0 to 10. The mean
      postoperative visual analog scale score at 3 months was 0.8. After the procedure,
      42 patients (87.5%) had a significant improvement in the visual analog scale
      score (P<.001); 5 (10.4%) had symptom improvement, although it was not
      statistically significant; and 1 (2.1%) remained unchanged. During follow-up, we
      observed 5 recurrences (10.4%) whereas de novo hydrocele formation was identified
      in 4 individuals (8.3%). CONCLUSION: Laparoscopic varicocelectomy is efficient in
      the treatment of symptomatic varicoceles with a low complication rate. However,
      careful patient selection is necessary because it appears that individuals
      presenting with sharp, radiating testicular pain and/or a low-grade varicocele
      are less likely to benefit from this procedure.

PMID- 25392635
TI  - Clonidine versus nitroglycerin infusion in laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic surgery offers the advantages of
      minimally invasive surgery; however, pneumoperitoneum and the patient's position
      induce pathophysiological changes that may complicate anesthetic management. We
      studied the effect of clonidine and nitroglycerin on heart rate and blood
      pressure, if any, in association with these drugs or the procedure, as well as
      the effect of these drugs, if any, on end-tidal carbon dioxide pressure and
      intraocular pressure. METHODS: Sixty patients (minimum age of 20 years and
      maximum age of 65 years, American Society of Anesthesiologists class I or II)
      undergoing laparoscopic cholecystectomy were randomized into 3 groups and given
      an infusion of clonidine (group I), nitroglycerin (group II), or normal saline
      solution (group III) after induction and before creation of pneumoperitoneum. We
      observed and recorded the following parameters: heart rate, mean arterial blood
      pressure, end-tidal carbon dioxide pressure, and intraocular pressure. The mean
      and standard deviation of the parameters studied during the observation period
      were calculated for the 3 treatment groups and compared by use of analysis of
      variance tests. Intragroup comparison was performed with the paired t test. The
      critical value of P, indicating the probability of a significant difference, was
      taken as < .05 for comparisons. RESULTS: Statistically significant differences in
      heart rate were observed among the various groups, whereas comparisons of mean
      arterial pressure, intraocular pressure, and end-tidal carbon dioxide pressure
      showed statistically significant differences only between groups I and III and
      between groups II and III. CONCLUSION: We found clonidine to be more effective
      than nitroglycerin at preventing changes in hemodynamic parameters and
      intraocular pressure induced by carbon dioxide insufflation during laparoscopic
      cholecystectomy. It was also found not to cause hypotension severe enough to stop
      the infusion and warrant treatment.

PMID- 25392636
TI  - Multidisciplinary treatment for thoracic and abdominopelvic endometriosis.
AB  - BACKGROUND AND OBJECTIVES: Thoracic endometriosis is a rare form of extragenital
      endometriosis with important clinical ramifications. Up to 80% of women with
      thoracic endometriosis have concomitant abdominopelvic endometriosis, yet the
      surgical treatment is usually performed with separate procedures. This is the
      largest published series of the combination of video-assisted thoracoscopic
      surgery and traditional laparoscopy for the treatment of abdominopelvic and
      thoracic endometriosis. The objectives of this series are to further evaluate the
      manifestations of thoracic endometriosis, assess the multidisciplinary surgical
      approach, and discuss our institution's protocols. METHODS: This is a
      retrospective, institutional review board-approved case series of 25 consecutive
      women who underwent combined video-assisted thoracoscopic surgery and traditional
      laparoscopy for the treatment of abdominopelvic, diaphragmatic, and thoracic
      endometriosis from January 1, 2008, to September 30, 2013. All surgeries were
      performed at a tertiary referral center by the same primary surgeons. Data were
      collected by chart review. RESULTS: Twenty-five patients were included, with a
      mean age of 37.7 years. Eighty percent of patients had catamenial chest pain, and
      in 40% this was their only chest complaint. Shoulder pain was noted in 40% of
      patients, catamenial pneumothorax in 24%, and hemoptysis in 12%. One hundred
      percent of patients were found to have endometriosis in the pelvis, 100% in the
      diaphragm, 64% in the chest wall, and 40% in the parenchyma. There were 2 major
      postoperative complications: 1 diaphragmatic hernia and 1 vaginal cuff hematoma.
      CONCLUSION: Clinical suspicion and preoperative assessment are crucial in the
      diagnosis of thoracic endometriosis and allow for a multidisciplinary approach.
      The combination of video-assisted thoracoscopic surgery and traditional
      laparoscopy for the treatment of endometriosis optimally addresses the pelvis,
      diaphragm, and thoracic cavity in a single operation.

PMID- 25392637
TI  - How to build a simple and safe laparoscopic hydatid evaluation system.
AB  - BACKGROUND: One of the most common problems faced in laparoscopic treatment of
      hydatid cysts is the difficulty in evacuating the particulate contents (daughter
      cysts and laminated membrane). Although various instruments and laparoscopic
      techniques have been described to evacuate the contents of hydatid cysts, most
      are not available at many surgical centers. METHODS: By assembling disposable,
      cheap, and available anesthesia equipment with common laparoscopic instruments, a
      laparoscopic system was made to evacuate the contents of a hydatid cyst. Ten
      patients with hepatic hydatid disease underwent laparoscopic surgery using this
      new hydatid system between June 2011 and January 2013. RESULTS: The procedure was
      completely straightforward. Twelve hydatid cysts (2 patients had 2 separated
      cysts) were evacuated without any spillage. All patients were followed for at
      least 8 months, with no evidence of recurrence. CONCLUSIONS: This simple
      apparatus, which can be assembled anywhere, was safely used to evacuate the
      contents of hydatid cysts without causing any spillage.

PMID- 25392638
TI  - Laparoscopically assisted vaginal hysterectomy for women with anterior wall
      adherence after cesarean section.
AB  - OBJECTIVES: To share and report experiences of using lateral approach technique
      to perform laparoscopically assisted vaginal hysterectomy (LAVH) for women with
      anterior wall adherence after cesarean section. METHODS: We analyzed a
      retrospective chart review of 47 women with anterior wall adhesion after a
      cesarean section who underwent LAVH from March 1st 2003 to March 31st 2012,
      selected from a total of 1967 women who underwent LAVH during that period.
      RESULTS: The median age of the patients was 42 years (range 34-56 years). The
      median operating time was 120 minutes (range 85-240 minutes), and the median
      weight of the removed uterus was 247 g (range 50-896 g). The median change in
      hemoglobin level was 2.0 g/dL (range 0-3.0 g/dL). The median hospital stay was
      3.0 days (range 2-6 days). There were complications in 2 cases: bladder injury in
      one and postoperative ileus in the other. There were no conversions to
      laparotomy. CONCLUSIONS: Lateral approach technique to make a pneumoperitoneum
      and to perform adhesiolysis is effective in LAVH for women with anterior wall
      adherence after cesarean section.

PMID- 25392639
TI  - SILS sigmoidectomy versus multiport laparoscopic sigmoidectomy for
      diverticulitis.
AB  - BACKGROUND AND OBJECTIVES: In this single-institution study, we aimed to compare
      the safety, feasibility, and outcomes of single-incision laparoscopic
      sigmoidectomy (SILSS) with multiport laparoscopic sigmoidectomy (MLS) for
      recurrent diverticulitis. METHODS: Between October 2011 and February 2013, 60
      sigmoidectomies were performed by the same surgeon. Forty patients had a MLS and
      20 patients had a SILSS. Outcomes were compared. RESULTS: Patient characteristics
      were similar. There was no difference in morbidity, mortality or readmission
      rates. The mean operative time was longer in the SILSS group (P=.0012). In a
      larger proportion of patients from the SILSS group, 2 linear staplers were needed
      for transection at the rectum (P=.006). The total cost of disposable items was
      higher in the SILSS group (P<.0001). No additional ports were placed in the SILSS
      group. Return to bowel function or return to oral intake was faster in the SILSS
      group (P=.0446 and P=.0137, respectively). Maximum pain scores on postoperative
      days 1 and 2 were significantly less for the SILSS group (P=.0014 and P=.047,
      respectively). Hospital stay was borderline statistically shorter in the SILSS
      group (P=.0053). SILSS was also associated with better cosmesis (P<.0011).
      CONCLUSION: SILSS is feasible and safe and is associated with earlier recovery of
      bowel function, a significant reduction in postoperative pain, and better
      cosmesis.

PMID- 25392641
TI  - Single-incision laparoscopic combined cholecystectomy and appendectomy.
AB  - BACKGROUND AND OBJECTIVES: Single-incision laparoscopic surgery is becoming more
      widely used, but few combined procedures have been reported. Herein we share our
      experience with single-incision laparoscopic combined cholecystectomy and
      appendectomy. METHODS: We reviewed data from 26 patients who underwent single
      incision laparoscopic combined cholecystectomy and appendectomy between May 1,
      2009 and June 1, 2013 at Shengjing Hospital. All the procedures were performed
      with conventional laparoscopic instruments placed through a single operating
      portal of entry created within the umbilicus. RESULTS: All the operations were
      successfully completed without conversion to conventional laparoscopic or open
      surgery. No intraoperative complications occurred. Patients were satisfied with
      the therapeutic and cosmetic outcomes. CONCLUSIONS: Single-incision laparoscopic
      combined cholecystectomy and appendectomy appear to be a technically feasible
      alternative to the standard laparoscopic procedure in simultaneous management of
      coexisting benign gallbladder and appendix pathologies. Larger studies are
      required to confirm these findings.

PMID- 25392640
TI  - How to reduce the laparoscopic colorectal learning curve.
AB  - BACKGROUND: The laparoscopic approach for colorectal pathologies is becoming more
      widely used, and surgeons have had to learn how to perform this new technique.
      The purpose of this work is to study the indicators of the learning curve for
      laparoscopic colectomy in a community hospital and to find when the group begins
      to improve. METHODOLOGY: From January 1 2005 to December 31 2012, 313 consecutive
      laparoscopic colorectal surgeries were performed (105 rectal and 208 colonic) by
      at least 60% of the same surgical team (6 members) in each operation. We evaluate
      the learning curve by moving averages and cumulative sums (CUSUM) for different
      variables related to the surgery outcomes. RESULTS: Moving average curves for
      postoperative stay, fasting, and second step analgesia show a stabilizing trend
      toward improvement as we get more experience. However, intensive care unit stay,
      number of lymph nodes achieved, and operating time did not show a clear
      decreasing tendency. CUSUM curves of conversion, specimens<12 lymph nodes, and
      complications all show a clear turning point marked on all the charts around the
      procedure 60, accumulating a positive trend toward improvement. The CUSUM curve
      of the "learning variable" shows this improvement point at procedure 70.
      CONCLUSIONS: The laparoscopic colectomy learning curve accelerates with a
      collective team involvement in each procedure. The CUSUM and moving average
      curves are useful for initial and ongoing monitoring of new surgical procedures.
      The markers of the learning curve evidenced in our study are the conversion rate,
      postoperative surgical morbidity, and the number of patients with a lymph node
      count<12. WHAT IS NEW IN THIS PAPER?: The significance of this study is the
      evaluation of the learning curve, in laparoscopic colorectal surgery, of a
      surgical team in a community hospital, using moving average and CUSUM curves.
      This study demonstrated that the number of patients needed to achieve skilful
      practice decreased when there is collective team involvement in each procedure.

PMID- 25392642
TI  - Long-term patient satisfaction with thermal balloon ablation for abnormal uterine
      bleeding.
AB  - BACKGROUND AND OBJECTIVE: Thermal balloon ablation is a minimally invasive
      surgical technique that can be used to treat abnormal uterine bleeding/heavy
      menstrual bleeding (AUB/HMB). Most published studies to date provide information
      on short-term patient satisfaction and outcomes. The purpose of this study was to
      determine long-term patient satisfaction after thermal balloon endometrial
      ablation 7 to 10 years postoperatively in a population previously surveyed at the
      Penn State Milton S. Hershey Medical Center at 1 to 5 years postoperatively.
      METHODS: Two-hundred fourteen patients were identified who underwent thermal
      balloon ablation at our institution between January 1, 2001 and December 31,
      2004. These patients were mailed a 2-page survey asking for information on
      demographics, patient satisfaction, postoperative bleeding patterns, and the need
      for subsequent surgery. Satisfaction rates, amenorrhea rates, and the rates of
      women who required hysterectomy were calculated as percentages. RESULTS: Ninety
      seven patients returned completed surveys. The survey response rate was 62%,
      excluding 57 surveys that were returned as undeliverable. The follow-up interval
      was 93 to 129 months. Eighty-seven percent of respondents were satisfied with the
      results of their procedure compared with 88% in the original study. Subsequent
      hysterectomy was required in 21.6% of women after 7 to 10 years compared with 9%
      after the 1- to 5-year follow-up period. Of the 76 women who did not undergo
      hysterectomy, 58% reported amenorrhea and 35.5% reported minimal to light
      bleeding. CONCLUSION: This study demonstrates a consistently high patient
      satisfaction rate with thermal balloon ablation at our institution at 7 to 11
      years postoperatively compared with 1 to 5 years postoperatively. The
      hysterectomy rate, however, was 2.4 times greater in the long-term follow-up
      period.

PMID- 25392643
TI  - Single-incision laparoscopic intraperitoneal onlay mesh repair for the treatment
      of multiple recurrent inguinal hernias.
AB  - INTRODUCTION: Despite an exponential rise in laparoscopic surgery for inguinal
      herniorrhaphy, overall recurrence rates have remained unchanged. Therefore, an
      increasing number of patients present with recurrent hernias after having failed
      anterior and laparoscopic repairs. This study reports our experience with single
      incision laparoscopic (SIL) intraperitoneal onlay mesh (IPOM) repair for these
      hernias. MATERIALS AND METHODS: All patients referred with multiply recurrent
      inguinal hernias underwent SIL-IPOM from November 1 2009 to October 30 2013. A
      2.5-cm infraumbilical incision was made and a SIL surgical port was placed
      intraperitoneally. Modified dissection techniques, namely, "chopsticks" and
      "inline" dissection, 5.5 mm/52 cm/30 degrees  angled laparoscope and conventional
      straight dissecting instruments were used. The peritoneum was incised above the
      symphysis pubis and dissection continued laterally and proximally raising an
      inferior flap, below a previous extraperitoneal mesh, while reducing any
      direct/indirect/femoral/cord lipoma before placement of antiadhesive mesh that
      was fixed into the pubic ramus as well as superiorly with nonabsorbable tacks
      before fixing its inferior border with fibrin sealant. The inferior peritoneal
      flap was then tacked back onto the mesh. RESULTS: There were 9 male patients who
      underwent SIL-IPOM. Mean age was 55 years old and mean body mass index was 26.8
      kg/m2. Mean mesh size was 275 cm2. Mean operation time was 125 minutes with
      hospital stay of 1 day and umbilical scar length of 21 mm at 4 weeks' follow-up.
      There were no intraoperative/postoperative complications, port-site hernias,
      chronic groin pain, or recurrence with mean follow-up of 20 months. CONCLUSIONS:
      Multiply recurrent inguinal hernias after failed conventional anterior and
      laparoscopic repairs can be treated safely and efficiently with SIL-IPOM.

PMID- 25392644
TI  - Contamination resulting from aerosolized fluid during laparoscopic surgery.
AB  - BACKGROUND AND OBJECTIVES: Aerosolized droplets of blood can travel considerable
      distances on release of intra-abdominal pressure during laparoscopic surgery.
      This creates an environmental hazard for members of the surgical team. This study
      describes and provides a method of measurement of aerosolized blood contamination
      during evacuation of the pneumoperitoneum in laparoscopic surgery. METHODS:
      Samples were measured by removing a trocar from the abdomen while a
      pneumoperitoneum of 15 mm Hg was present. A white poster board was placed 24
      inches above the incision to catch the released blood spatter. By use of machine
      vision, luminol fluorescence, and computerized spatial analysis, data from the
      boards were recorded, analyzed, and scored based on the distance, size, and
      quantity of particulate contamination. RESULTS: We analyzed 27 boards. Spatter
      was present on every board. The addition of luminol to the boards increased the
      amount of visible spatter. Most tests created <1000 blood spatters. Fluids are
      typically ejected as a fine mist. Every test included at least 1 blood spatter.
      The range of the average blood spatter size was 0.53*10(-3) to 7.11*10(-3) sq in.
      The amount of spatter detected did not show any apparent correlation with the
      patient's body mass index, the estimated blood loss, or the type of operation
      performed. CONCLUSIONS: Evacuation of the pneumoperitoneum during laparoscopic
      surgery results in consistent contamination. Most blood spatter is not visible to
      the naked eye. Our results suggest that all surgical participants should wear
      appropriate protective barriers and conscious measures should be undertaken to
      prevent environmental contamination during pneumoperitoneal evacuation.

PMID- 25392645
TI  - Cost-effectiveness of office hysteroscopy for abnormal uterine bleeding.
AB  - BACKGROUND AND OBJECTIVES: Office diagnostic hysteroscopy allows physicians to
      directly view the endometrial cavity, tubal ostia, and endocervical canal without
      taking the patient to the operating room (OR). We sought to determine whether
      office hysteroscopy performed to evaluate abnormal uterine bleeding decreases the
      need for hysteroscopy performed in the OR and the associated financial and risk
      implications. METHODS: One hundred thirty patients who underwent office
      diagnostic hysteroscopy between January 2009 and March 2012 at 2 outpatient
      clinics in an academic university setting were identified. Records were reviewed
      from paper charts and electronic medical records. Hospital charts for patients
      who required hysteroscopy in the OR were reviewed as well. Charge estimates were
      obtained from our billing department. These results were analyzed for review of
      the data. RESULTS: Seventy-five of the 130 women who underwent diagnostic office
      hysteroscopy for abnormal bleeding did not need to undergo hysteroscopy in the
      OR. This represents estimated savings of $1498 per patient (95% confidence
      interval, $1051-$1923) in procedure charges. Among the 55 women who underwent OR
      hysteroscopy, there was 71% agreement between findings on hysteroscopy in the
      office and in the OR. CONCLUSION: Office hysteroscopy is a useful diagnostic tool
      that can help decrease the rate of diagnostic hysteroscopy in the OR under
      anesthesia when used in a select patient population.

PMID- 25392646
TI  - Transumbilical single-incision laparoscopic resection of focal hepatic lesions.
AB  - BACKGROUND AND OBJECTIVES: Transumbilical single-incision laparoscopic surgery
      (SILS) is gaining in popularity as a minimally invasive technique. The reduced
      pain and superior cosmetic appearance it affords make it attractive to many
      patients. For this study, we focused on SILS, analyzing the outcomes of
      transumbilical single-incision laparoscopic liver resection (SILLR) achieved at
      our institution between January 2010 and February 2013. PATIENTS AND METHODS: Pre
      and postoperative data from 17 patients subjected to transumbilical SILLR for
      various hepatic lesions (8 hemangiomas, 2 hepatocellular carcinomas, 2
      metastases, 2 calculi of left intrahepatic duct, and 3 adenomas) were assessed.
      Altogether, eight wedge resections, seven left lateral lobectomies, a combination
      wedge resection/left lateral lobectomy, and a proximal left hemihepatectomy
      segmentectomy were performed, as well as four simultaneous laparoscopic
      cholecystectomies. In each instance, three ports were installed through an
      umbilical incision. Once vessels and bleeding were controlled, the lesion(s) were
      resected with 5-mm margins of normal liver. Resected tissues were then bagged and
      withdrawn through the umbilical incision. The follow-up period lasted for a
      minimum of 6 months. RESULTS: All 17 patients were successfully treated through a
      single umbilical incision. The procedures required 55 to 185 minutes to complete,
      with blood loss of 30 to 830 mL. Subjects regained bowel activity 0.8 to 2.3 days
      postoperatively and were discharged after 3 to 10 days. There were few
      complications (23.5%), limited to pleural effusion, wound infection, and
      incisional hernia. CONCLUSIONS: Transumbilical SILLR is challenging to perform
      through conventional laparoscopic instrumentation. The risk of bleeding and
      technical difficulties is high for lesions of the posterosuperior hepatic
      segment. Surgical candidates should be carefully selected to optimize the
      benefits of this technique.

PMID- 25392647
TI  - The da vinci robot system eliminates multispecialty surgical trainees' hand
      dominance in open and robotic surgical settings.
AB  - BACKGROUND AND OBJECTIVES: Handedness, or the inherent dominance of one hand's
      dexterity over the other's, is a factor in open surgery but has an unknown
      importance in robot-assisted surgery. We sought to examine whether the robotic
      surgery platform could eliminate the effect of inherent hand preference. METHODS:
      Residents from the Urology and Obstetrics/Gynecology departments were enrolled.
      Ambidextrous and left-handed subjects were excluded. After completing a
      questionnaire, subjects performed three tasks modified from the Fundamentals of
      Laparoscopic Surgery curriculum. Tasks were performed by hand and then with the
      da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, California).
      Participants were randomized to begin with using either the left or the right
      hand, and then switch. Left:right ratios were calculated from scores based on
      time to task completion. Linear regression analysis was used to determine the
      significance of the impact of surgical technique on hand dominance. RESULTS: Ten
      subjects were enrolled. The mean difference in raw score performance between the
      right and left hands was 12.5 seconds for open tasks and 8 seconds for robotic
      tasks (P<.05). Overall left-right ratios were found to be 1.45 versus 1.12 for
      the open and robot tasks, respectively (P<.05). Handedness significantly differed
      between robotic and open approaches for raw time scores (P<.0001) and left-right
      ratio (P=.03) when controlling for the prior tasks completed, starting hand,
      prior robotic experience, and comfort level. These findings remain to be
      validated in larger cohorts. CONCLUSION: The robotic technique reduces hand
      dominance in surgical trainees across all task domains. This finding contributes
      to the known advantages of robotic surgery.

PMID- 25392648
TI  - Robotic surgery training in gynecologic fellowship programs in the United States.
AB  - BACKGROUND AND OBJECTIVES: The increasing use and acceptance of robotic platforms
      calls for the need to train not only established surgeons but also residents and
      fellow trainees within the context of the traditional residency and fellowship
      program. Our study aimed to clarify the current status of robotic training in
      gynecologic fellowship programs in the United States. METHODS: This was a Web
      based survey of four gynecology fellowship programs in the United States from
      November 2010 to March 2011. Programs were selected based on their geographic
      areas. A questionnaire with 43 questions inquiring about robotic surgery
      performance and training was sent to the programs and either a fellow or the
      fellowship director was asked to complete. Participation was voluntary. RESULTS:
      We had 102 responders (18% respond rate) with an almost equal response rate from
      all four gynecologic fellowships, with a median response rate of 25% (range 21
      29%). Minimally Invasive Surgery (MIS) and Gynecologic Oncology (Gyn Onc)
      fellowships had the highest rate of robotic training in their fellowship
      curriculum-95% and 83%, respectively. Simulator training was used as a training
      tool in 74% of Female Pelvic Medicine and Reconstructive Surgery (FPMRS);
      however, just 22% of Reproductive Endocrinology and Infertility fellowships had
      simulator training. Eighty-seven percent of Gyn Onc fellows graduate with >50
      robotic cases, but this was 0% for Reproductive Endocrinology Infertility
      fellows. CONCLUSION: Our study showed that the use of a robotic system was built
      into fellowship curriculum of >80% of MIS and Gyn Onc fellowship programs that
      were entered in our study. Simulator training has been used widely in Ob&Gyn
      fellowship programs as part of their robotic training curriculum.

PMID- 25392649
TI  - Antimullerian hormone level and endometrioma ablation using plasma energy.
AB  - OBJECTIVE: To investigate the impact of ovarian endometrioma vaporization using
      plasma energy on antimullerian hormone (AMH) level. METHOD: We report a
      prospective, noncomparative series (NCT01596985). Twenty-two patients with
      unilateral ovarian endometriomas>=30 mm, with no surgical antecedent and no
      ongoing pregnancy, underwent vaporization of ovarian endometriomas using plasma
      energy during the period of November 29, 2010 to November 28, 2012. We assessed
      AMH levels before surgery, 3 months postoperatively, and at the end of follow-up.
      RESULTS: The mean length of postoperative follow-up was 18.2+/-8 months. AMH
      level significantly varied through the 3 assessments performed in the study, as
      the mean values+/-SD were 3.9+/-2.6 ng/mL before the surgery, 2.3+/-1.1 ng/mL at
      3 months, and 3.1+/-2.2 ng/mL at the end of the follow-up (P=.001). There was a
      significant increase from 3 months postoperatively to the end of follow-up
      (median change 0.7 ng/mL, P=.01). Seventy-one percent of patients had an AMH
      level>2 ng/mL at the end of the follow-up versus 76% before the surgery (P=1).
      During the postoperative follow-up, 11 patients tried to conceive, of whom 8
      (73%) became pregnant. CONCLUSIONS: The ablation of unilateral endometriomas is
      followed in a majority of cases by a significant decrease in AMH level 3 months
      after surgery. In subsequent months, this level progressively increases, raising
      questions about the real factors that impact postoperative ovarian AMH
      production.

PMID- 25392650
TI  - Laparoscopic repair of paraesophageal hernias.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopy has quickly become the standard surgical
      approach to repair paraesophageal hernias. Although many centers routinely
      perform this procedure, relatively high recurrence rates have led many surgeons
      to question this approach. We sought to evaluate outcomes in our cohort of
      patients with an emphasis on recurrence rates and symptom improvement and their
      correlation with true radiologic recurrence seen on contrast imaging. METHODS: We
      retrospectively identified 126 consecutive patients who underwent laparoscopic
      repair of a large paraesophageal hernia between 2000 and 2010. Clinical outcomes
      were reviewed, and data were collected regarding operative details, perioperative
      and postoperative complications, symptoms, and follow-up imaging. Radiologic
      evidence of any size hiatal hernia was considered to indicate a recurrence.
      RESULTS: There were 95 female and 31 male patients with a mean age (+/-standard
      deviation) of 71+/-14 years. Laparoscopic repair was completed successfully in
      120 of 126 patients, with 6 operations converted to open procedures. Crural
      reinforcement with mesh was performed in 79% of patients, and 11% underwent a
      Collis gastroplasty. Fundoplications were performed in 90% of patients: Nissen
      (112), Dor (1), and Toupet (1). Radiographic surveillance, obtained at a mean
      time interval of 23 months postoperatively, was available in 89 of 126 patients
      (71%). Radiographic evidence of a recurrence was present in 19 patients (21%).
      Reoperation was necessary in 6 patients (5%): 5 for symptomatic recurrence (4%)
      and 1 for dysphagia (1%). The median length of stay was 4 days. CONCLUSION:
      Laparoscopic paraesophageal hernia repair results in an excellent outcome with a
      short length of stay when performed at an experienced center. Radiologic
      recurrence is observed relatively frequently with routine surveillance; however,
      many of these recurrences are small, and few patients require correction of the
      recurrence. Furthermore, these small recurrent hernias are often asymptomatic and
      do not seem to be associated with the same risk of severe complications
      developing as the initial paraesophageal hernia.

PMID- 25392651
TI  - Pregnancy outcomes after myomectomy with polytetrafluoroethylene placement.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to report preliminary data
      on pregnancy outcomes after myomectomy with placement of an expanded
      polytetrafluoroethylene adhesion barrier membrane. METHODS: In this retrospective
      case series, 68 women who underwent myomectomy with expanded
      polytetrafluoroethylene membrane placement between January 1, 2003, and December
      31, 2009, were identified. Of these women, 15 subsequently had documented
      pregnancies and were included in the final dataset. RESULTS: Eighteen pregnancies
      were documented among 15 women. There were no reported cases of preterm labor,
      preterm premature rupture of membranes, or uterine rupture. CONCLUSION: In this
      case series, there were no documented cases of preterm labor, preterm premature
      rupture of membranes, or uterine rupture after myomectomy with expanded
      polytetrafluoroethylene membrane placement.

PMID- 25392652
TI  - Laparoscopy and complicated meckel diverticulum in children.
AB  - BACKGROUND AND OBJECTIVES: Meckel diverticulum can present with a variety of
      complications but is often found incidentally during other surgical procedures.
      The role of laparoscopy in the management of Meckel diverticulum is established.
      We reviewed our experience with complicated cases of Meckel diverticulum in
      children managed with laparoscopy. METHODS: A 15-year retrospective chart review
      revealed 14 cases of complicated Meckel diverticulum managed with laparoscopy.
      Incidentally found Meckel diverticulum and cases done by laparotomy were
      excluded. Ages varied from 2 years to 16 years old. There were 10 males and four
      females. Eight cases had small bowel obstruction; of those, three had extensive
      intestinal gangrene. Four cases had significant rectal bleeding, three had acute
      diverticulitis, and two had intussusception caused by the diverticulum. RESULTS:
      Eleven cases were treated with laparoscopic Meckel diverticulectomy and three
      with laparoscopic-assisted bowel resection because of extensive gangrene of the
      intestine. Two of the three cases with significant intestinal gangrene returned
      several weeks later with small bowel obstruction secondary to adhesions. They
      were successfully managed with laparoscopic lysis of adhesions. There were no
      other complications. CONCLUSIONS: Laparoscopy is safe and effective in the
      management of complicated Meckel diverticulum in children. Most cases can be
      managed with simple diverticulectomy. Laparoscopy is useful when the diagnosis is
      uncertain. When extensive gangrene is present, laparoscopy can help to mobilize
      the intestine and evaluate the degree of damage, irrigate and cleanse the
      peritoneal cavity, and minimize the incision necessary to accomplish the bowel
      resection.

PMID- 25392653
TI  - Robotic-laparoscopic rectal cancer excision versus traditional laparoscopy.
AB  - BACKGROUND AND OBJECTIVES: Robotic surgery has been advocated for the radical
      excision of rectal cancer. Most data supporting its use have been reported from
      European and Asian centers, with a paucity of data from the United States
      documenting clear advantages of the robotic technique. This study compares the
      short-term outcome of robotic versus laparoscopic surgery. METHODS: Consecutive
      patients who underwent laparoscopic (group 1) or robotic (group 2) rectal cancer
      excision at a single institution over a 2-year period were retrospectively
      reviewed. The main outcome measures were operative time, blood loss, conversion
      rates, number of lymph nodes, margin positivity, length of hospital stay,
      complications, and readmission rates. RESULTS: Forty-two patients were analyzed.
      The median operative time was shorter in group 1 than that in group 2 (240
      minutes vs 260 minutes, P=.04). No difference was noted in blood loss,
      transfusion rates, intraoperative complications, or conversion rates. There was
      no difference in circumferential or distal margin positivity. The median length
      of stay was shorter in group 1 (5 days vs 6 days, P=.05). The 90-day complication
      rate was similar in both groups (33% vs 43%, P=.75), but there was a trend toward
      more anastomotic leaks in group 1 (14% vs 0%, P=.23). Similarly, a non
      statistically significant trend toward a higher readmission rate was noted in
      group 1 (24% vs 5%, P=.18). CONCLUSION: Robotic rectal cancer excision yielded a
      longer operative time and hospital length of stay, although immediate oncologic
      results were comparable. The need for randomized data is critical to determine
      whether the added resource utilization in robotic surgery is justifiable.

PMID- 25392654
TI  - Simplifying laparoscopic nephrectomy: the inferior approach with en bloc stapling
      of the renal hilum.
AB  - INTRODUCTION: Laparoscopic nephrectomy (LN) is likely the most common
      laparoscopic procedure performed by general urologists without formal
      laparoscopic training. The traditional technique is cumbersome because it entails
      making an early approach to the hilum with the risk of bleeding and need for
      conversion. We perform a different technique that we believe is simpler to learn
      and to teach. It consists of a complete dissection of the inferior and posterior
      aspects of the kidney, followed by en bloc stapling of the renal hilum. The
      present report is a detailed description of our technique including outcomes and
      complications. MATERIALS AND METHODS: Perioperative data of 129 consecutive
      patients who underwent LN between November 2003 and September 2007 were
      prospectively collected and retrospectively reviewed. Complications were reported
      using the Clavien classification system, and follow-up was performed according to
      our institution's protocol and included physical examination, blood count, blood
      chemistry, and renal function tests at every visit, in addition to abdominal
      computed tomography scan six months after surgery. Additional imaging was
      scheduled according to disease stage and grade. RESULTS: Mean patient age, tumor
      size, and operative time were 63+/-15.6 years, 6.3+/-2.4 cm, and 128+/-41.4
      minutes, respectively. Median estimated blood loss was 0 mL (0.200). Conversion
      to open surgery occurred in 3.1% of patients, and 8% of the patients had a blood
      transfusion. Complications were recorded in 26% of the patients; 91% of them had
      Clavien grade scores of 1 or 2. CONCLUSION: We present a standardized technique
      for LN. Its main advantage is that postpones any manipulation of the hilum to a
      later step during the procedure when it is easy to identify and control. This
      decreases early bleeding and main vascular complications.

PMID- 25392655
TI  - Single-port parastomal hernia repair by using 3-D textile implants.
AB  - BACKGROUND: Parastomal hernias (PSHs) are a frequent complication and remain a
      surgical challenge. We present a new option for single-port PSH repair with
      equilateral stoma relocation using preshaped, prosthetic 3-dimensional implants
      and flat mesh insertion in intraperitoneal onlay placement for additional
      augmentation of the abdominal wall. METHODS: We describe our novel technique in
      detail and performed an analysis of prospectively collected data from patients
      who underwent single-port PSH repair, focusing on feasibility, conversions, and
      complications. RESULTS: From September 2013 to January 2014, 9 patients with
      symptomatic PSHs were included. Two conversions to reduced-port laparoscopy using
      a second 3-mm trocar were required because of difficult adhesiolysis, dissection,
      and reduction of the hernia sac content. No major intra- or postoperative
      complications or reoperations were encountered. One patient incurred a peristomal
      wound healing defect that could be treated conservatively. CONCLUSION: We found
      that single-port PSH repair using preshaped, elastic 3-dimensional devices and
      additional flat mesh repair of the abdominal wall is feasible, safe, and
      beneficial, relating to optimal coverage of unstable stoma edges with wide
      overlap to all sides and simultaneous augmentation of the midline in the IPOM
      technique. The stoma relocation enables prolapse treatment and prevention. The
      features of a modular and rotatable multichannel port system offer benefits in
      clear dissection ongoing from a single port. Long-term follow-up data on an
      adequate number of patients are awaited to examine efficacy.

PMID- 25392656
TI  - Pain medication requirements after sacropexy and combination interventions.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic surgery is associated with reduced
      morbidity, and postoperative pain is reduced. The aim of this study was to assess
      postoperative pain intensity, analgesic requirements, and the influence of
      cofactors after laparoscopic sacral colpopexy. METHODS: The study assessed 287
      patients treated with laparoscopic sacropexy for genital prolapse with a Pelvic
      Organ Prolapse Quantification grade>1. Patients were asked to evaluate their pain
      postoperatively using a 4-point verbal pain rating scale. In addition, medical
      records were analyzed regarding the requirement for analgesic medication.
      RESULTS: Patients distinguished between abdominal pain and shoulder pain after
      laparoscopy. Abdominal pain reached maximum severity on day 1 and showed a good
      response to nonsteroidal antiphlogistics, whereas shoulder pain was rarely found
      (6.27%). Of the patients, 38% required no pain treatment or required 1 dose at
      most. The need for pain medication reached its climax on day 1 and decreased
      during the 5 following days. Non-opioid analgesics provided a sufficient
      therapeutic effect. CONCLUSION: Laparoscopic sacropexy is associated with a
      moderate degree of postoperative pain. Non-opioid analgesics should be preferred
      as first-line therapy. The typical shoulder-tip pain showed only a low prevalence
      in our study group. From our point of view, the low rate of shoulder-tip pain
      corresponded with the low intra-abdominal carbon dioxide pressure.

PMID- 25392657
TI  - The outcome of self-expanding metal stents in elderly patients.
AB  - BACKGROUND AND OBJECTIVES: Emergency surgery for large bowel obstruction is
      associated with high morbidity and mortality rates, especially in elderly
      patients. Colonic self-expanding metal stents may provide temporary relief of
      obstructions and enable preoperative evaluation. The aim of this retrospective
      study was to assess the clinical outcomes of emergency stenting in elderly
      patients with large bowel obstructions. METHODS: Between 1997 and 2010, patients
      presenting with large bowel obstructions were treated predominantly with self
      expanding metal stent insertion. Clinical data, including age, site of
      obstruction, success rate, and surgery and mortality rates, were collected.
      Patients were divided into 3 groups (I, II, and III) according to age: <69, 70 to
      79, or >80 years. RESULTS: One hundred thirty-two consecutive patients underwent
      stent implantation, with a mean age of 72.1 years (range, 28-95 years). Similar
      diversity of sex, indication, and stricture location was found. There were no
      significant differences in clinical success (88.7%, 73.8%, and 78.4%, P=.16) and
      stent-related mortality (2.1%, 3.3%, and 3.6%, P=1.00). Similar rates of stoma
      creation were also found (59.3%, 46.7%, and 60.0%, P=.76). In contrast, rates of
      surgery were lower in older patients (50.9%, 38.1%, and 13.5%, P=.0013), and
      mortality during the same admission was significantly higher in patients>70 years
      of age (4.0%, 15.0%, and 22.2%, P=.027). Kaplan-Meier 30-day survival curves for
      the 3 groups showed a trend toward earlier death among patients>70 years of age.
      CONCLUSIONS: This study demonstrates that stenting provides similar success rates
      in all age groups but is associated with higher mortality rates in older
      patients.

PMID- 25392658
TI  - Tranexamic acid and hyaluronate/carboxymethylcellulose create cell injury.
AB  - BACKGROUND AND OBJECTIVES: Postoperative pelvic adhesions are associated with
      chronic pelvic pain, dyspareunia, and infertility. The aim of this study was to
      evaluate the adhesion prevention effects of tranexamic acid (TA) and
      hyaluronate/carboxymethylcellulose (HA/CMC) barrier in the rat uterine horn
      models on the basis of macroscopic and microscopic adhesion scores and
      histopathological as well as biochemical parameters of inflammation. METHODS:
      Twenty-one Wistar rats were randomly divided into 3 groups. Ten lesions were
      created on the antimesenteric surface of both uterine horns by bipolar cautery.
      Three milliliters of 0.9% sodium chloride solution were administered in the
      control group. A single layer of 2*2 cm HA/CMC was plated in group 2. Two
      milliliters of TA was applied in the last group. All rats were sacrificed at
      postoperative day 21. RESULTS: No significant difference was found among the
      control group, the HA/CMC group, and the TA group in terms of macro-adhesion
      score (P=.206) and microadhesion score (P=.056). No significant difference was
      found among the 3 groups in terms of inflammation score (P=.815) and inflammatory
      cell activity (P=.835). Malondialdehyde levels were significantly lower in the
      control group than in the TA group and HA/CMC group (P=.028). Superoxide
      dismutase and glutathione S-transferase activities were found to be higher in the
      control group than in the TA group (P=.005) and HA/CMC group (P=.009).
      CONCLUSIONS: TA and HA/CMC had no efficacy in preventing macroscopic or
      microscopic adhesion formation and decreasing inflammatory cell activity or
      inflammation score in our rat models. TA and HA/CMC increased the levels of free
      radicals and reduced the activities of superoxide dismutase and glutathione S
      transferase enzymes, which act to reduce tissue injury.

PMID- 25392659
TI  - Complications of laparoscopic gynecologic surgery.
AB  - BACKGROUND AND OBJECTIVES: To analyze the frequency of complications during
      laparoscopic gynecologic surgery and identify associated risk factors. METHODS: A
      descriptive observational study was performed between January 2000 and December
      2012 and included all gynecologic laparoscopies performed at our center.
      Variables were recorded for patient characteristics, indication for surgery,
      length of hospital stay (in days), major and minor complications, and conversions
      to laparotomy. To identify risk factors and variables associated with
      complications, crude and adjusted odds ratios were calculated with unconditional
      logistic regression. RESULTS: Of all 2888 laparoscopies included, most were
      procedures of moderate difficulty (adnexal surgery) (54.2%). The overall
      frequency of major complications was 1.93%, and that of minor complications was
      4.29%. The level of technical difficulty and existence of prior abdominal surgery
      were associated with a higher risk of major complications and conversions to
      laparotomy. CONCLUSION: Laparoscopic gynecologic surgery is associated with a low
      frequency of complications but is a procedure that is not without risk. Greater
      technical difficulty and prior surgery were factors associated with a higher
      frequency of complications.

PMID- 25392660
TI  - Laparoscopic adrenalectomy for solitary adrenal metastasis from lung cancer.
AB  - BACKGROUND AND OBJECTIVES: Several studies have been reported on the problem of
      determining when laparoscopic adrenalectomy is indicated for solitary adrenal
      metastasis of malignant tumors. Our efforts at answering this question constitute
      the basis of this report. METHODS: From June 2010 to June 2011, laparoscopic
      adrenalectomy was performed in 10 lung cancer patients with solitary adrenal
      metastases (5 adenocarcinomas, 1 squamous cell carcinoma, 1 large cell carcinoma,
      1 small cell carcinoma, and 2 pleomorphic carcinomas). The surgical results of
      all 10 patients were examined. RESULTS: Adrenal swelling was detected by computed
      tomography in all patients except 1 case of pleomorphic carcinoma. The findings
      of positron emission tomography-computed tomography were positive in 8 patients,
      including the 2 cases with pleomorphic carcinomas. Laparoscopic surgery was
      successfully performed in 9 cases. In the eighth patient (a case of pleomorphic
      carcinoma with adrenal swelling), laparoscopic adrenalectomy was attempted but
      conversion to open surgery was required because of clear evidence of pancreatic
      invasion. CONCLUSION: The results obtained in this study, along with other
      published reports, support 4 criteria as operative indications for laparoscopic
      adrenalectomy in solitary adrenal metastasis from the lung: (1) the primary lung
      cancer is resected or can be cured by radical chemotherapy, (2) metastasis is
      limited to the adrenal gland only, (3) adrenal metastasis does not invade the
      surrounding organs, and (4) the size of the adrenal tumor does not exceed 10 cm.
      In cases of pleomorphic carcinoma, laparoscopic adrenalectomy should be performed
      when positron emission tomography-computed tomography results are positive.

PMID- 25392661
TI  - Laparoscopic hernia: umbilical-pubis length versus technical difficulty.
AB  - Laparoscopic hernia repair is more difficult than open hernia repair. The totally
      extraperitoneal procedure with 3 trocars on the midline is more comfortable for
      the surgeon. We studied the impact of the length between the umbilicus and the
      pubis on the totally extraperitoneal procedure (95 hernias operated on in 70
      patients). This length did not influence the totally extraperitoneal procedure in
      this study. BACKGROUND: The laparoscopic repair of hernias is considered to be
      difficult especially for the totally extra-peritoneal technique (TEP) due to a
      limited working space and different appreciation of the usual anatomical
      landmarks seen through an anterior approach. The aim of our study has been to
      answer a question: does the umbilical-pubic distance, which influences the size
      of the mesh, affect the TEP technique used in the treatment of inguinal hernias?
      METHODS: From January 2001 to May 2011, the umbilical-pubic (UP) distance was
      measured with a sterile ruler graduated in centimeters in all patients who
      underwent a symptomatic inguinal hernia by the TEP technique in two hernia
      surgery centers. The sex, age, BMI, hernia type, UP distance, operation time,
      hospital stay and complications were prospectively examined based on the medical
      records. RESULTS: Seventy patients underwent 95 inguinal hernia repairs by the
      TEP technique. The umbilical-pubic distance average was 14 cm (10 to 22) and a 25
      kg/m2 (16-30) average concerning the body mass index (BMI). Seventy percent of
      patients were treated on an outpatient basis. The postoperative course was very
      simple. There was no recurrence of hernia within this early postoperative period.
      CONCLUSION: The umbilical-pubic distance had no influence on the production of
      TEP with 3 trocars on the midline in this study.

PMID- 25392662
TI  - Updated hysterectomy surveillance and factors associated with minimally invasive
      hysterectomy.
AB  - BACKGROUND AND OBJECTIVES: The goal of this study is to obtain updated
      surveillance statistics for hysterectomy procedures in the United States and
      identify factors associated with undergoing a minimally invasive approach to
      hysterectomy. METHODS: A cross-sectional analysis of the 2009 United States
      Nationwide Inpatient Sample was performed. Subjects included all women aged 18
      years or older who underwent hysterectomy of any type. Logistic regression and
      multivariate analyses were performed to assess the proportion of hysterectomies
      performed by various routes, as well as factors associated with undergoing
      minimally invasive surgery (laparoscopic, vaginal, or robotic). RESULTS: A total
      of 479,814 hysterectomies were performed in the United States in 2009, 86.6% of
      which were performed for benign indications. Among the hysterectomies performed
      for benign indications, 56% were completed abdominally, 20.4% were performed
      laparoscopically, 18.8% were performed vaginally, and 4.5% were performed with
      robotic assistance. Factors associated with decreased odds of a minimally
      invasive hysterectomy included the following: minority race (P<.0001), fibroids
      (P<.0001), concomitant adnexal surgery (P<.0001), self-pay (P=.01) or Medicaid as
      insurer (P<.0001), and increased severity of illness (P<.0001). Factors
      associated with increased odds of a minimally invasive hysterectomy included the
      following: age>50 years (P<.0001), prolapse or menstrual disorder (P<.0001),
      median household income of $48,000-$62,999 (P=.007) or >=$63,000 (P=.009), and
      location in the West (P=.02). A length of stay>1 day was most common in abdominal
      hysterectomy cases (96.1%), although total mean charges were highest for robotic
      cases ($38,161). CONCLUSION: The US hysterectomy incidence in 2009 decreased from
      prior years' reports, with an increasing frequency of laparoscopic and robotic
      approaches. Racial and socioeconomic factors influenced hysterectomy mode.

PMID- 25392663
TI  - Robot-assisted sleeve gastrectomy in morbidly obese versus super obese patients.
AB  - BACKGROUND AND OBJECTIVES: This study evaluates our technique for robot-assisted
      sleeve gastrectomy for morbidly obese and super obese patients and our outcomes.
      METHODS: A retrospective analysis of patients who underwent robot-assisted sleeve
      gastrectomy at a single center was performed. The procedure was performed with
      the da Vinci Si HD Surgical System (Intuitive Surgical, Sunnyvale, California).
      The staple line was imbricated with No. 2-0 polydioxanone in all cases. The super
      obese (body mass index>=50 kg/m2) subset of patients was compared with the
      morbidly obese group in terms of demographic characteristics, comorbidities,
      operative times, perioperative complications, and excess body weight loss.
      RESULTS: A total of 35 patients (15 female and 20 male patients) with a mean body
      mass index of 48.17+/-11.7 kg/m2 underwent robot-assisted sleeve gastrectomy. Of
      these patients, 11 were super obese and 24 were morbidly obese. The mean
      operative time was 116.3+/-24.7 minutes, and the mean docking time was 8.9+/-5.4
      minutes. Mean blood loss was 19.36+/-4.62 mL, and there were no complications,
      conversions, or perioperative deaths. When compared with the morbidly obese
      patients, the super obese patients showed no significant difference in operative
      time, blood loss, and length of hospital stay. There was a steep decline in
      operating room times after 10 cases of robot-assisted sleeve gastrectomy.
      CONCLUSION: This study shows the feasibility and safety of robot-assisted sleeve
      gastrectomy. Robotic assistance might help overcome the operative difficulties
      encountered in super obese patients. It shows a rapid reduction in operative
      times with the growing experience of the entire operative team. Robot-assisted
      sleeve gastrectomy can be a good procedure by which to introduce robotics in a
      bariatric surgery center before going on to perform Roux-en-Y gastric bypass and
      revision procedures.

PMID- 25392664
TI  - Outcomes of a third bariatric procedure for inadequate weight loss.
AB  - BACKGROUND AND OBJECTIVES: The robust volume of bariatric surgical procedures has
      led to significant numbers of patients requiring reoperative surgery because of
      undesirable results from primary operations. The aim of this study was to assess
      the feasibility, safety, and outcomes of the third bariatric procedure after
      previous attempts resulted in inadequate results. METHODS: We retrospectively
      identified patients who underwent a third bariatric procedure for inadequate
      weight loss or significant weight regain after the second operation. Data were
      analyzed to establish patient demographic characteristics, perioperative
      parameters, and postoperative outcomes. RESULTS: A total of 12 patients were
      identified. Before the first, second, and third procedures, patients had a mean
      body mass index of 67.1+/-29.3 kg/m2, 60.9+/-28.3 kg/m2, and 49.4+/-19.8 kg/m2,
      respectively. The third operations (laparoscopic in 10 and open in 2) included
      Roux-en-Y gastric bypass (n=5), revision of pouch and/or stoma of Roux-en-Y
      gastric bypass (n=3), limb lengthening after Roux-en-Y gastric bypass (n=3), and
      sleeve gastrectomy (n=1). We encountered 5 early complications in 4 patients, and
      early reoperative intervention was needed in 2 patients. At 1-year follow-up, the
      excess weight loss of the cohort was 49.4%+/-33.8%. After a mean follow-up time
      of 43.0+/-28.6 months, the body mass index of the cohort reached 39.9+/-20.8
      kg/m2, which corresponded to a mean excess weight loss of 54.4%+/-44.0% from the
      third operation. At the latest follow-up, 64% of patients had excess weight
      loss>50% and 45% had excess weight loss>80%. CONCLUSION: Reoperative bariatric
      surgery can be carried out successfully (often laparoscopically), even after 2
      previous weight loss procedures.

PMID- 25392665
TI  - Comparison of ovulation induction protocols after endometrioma resection.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the in vitro
      fertilization (IVF) outcomes of long gonadotropin-releasing hormone agonist (GnRH
      a) and GnRH-antagonist (GnRH-ant) protocols in endometriosis patients who have
      undergone laparoscopic endometrioma resection surgery. To our knowledge, there is
      no study in the current literature that compares the effectiveness of long GnRH-a
      and GnRH-ant protocols in management of IVF cycles in endometriosis patients who
      underwent laparoscopic endometrioma resection surgery. METHODS: Eighty-six
      patients with stage III to IV endometriosis who had undergone laparoscopic
      resection surgery for endometrioma were divided into 2 groups: those who had
      ovarian stimulation with a long GnRH-a protocol (n=44), and those who had ovarian
      stimulation with a GnRH-ant protocol (n=42). RESULTS: The number of follicles on
      human chorionic gonadotropin injection day, duration of hyperstimulation, number
      of retrieved metaphase II oocytes, and total number of grade 1 embryos were
      statically significantly higher in the long GnRH-a protocol. There were no
      significant differences in positive beta-human chorionic gonadotropin pregnancy
      rates (25% vs 21.4%; P=.269) and ongoing pregnancy rates per patient (20.5% vs
      19.1%; P=.302) between the 2 protocols. CONCLUSIONS: Long GnRH-a and GnRH-ant
      protocols both present similar IVF outcomes in patients with endometriosis who
      have undergone laparoscopic endometrioma resection surgery. A long GnRH-a
      protocol may lead to a higher number of embryos that can be cryopreserved,
      providing the possibility of additional embryo transfers without having to go
      through the process of ovarian stimulation again.

PMID- 25392666
TI  - Ureteral injury after laparoscopic versus open colectomy.
AB  - BACKGROUND AND OBJECTIVES: Ureteral injury is an infrequent but potentially
      lethal complication of colectomy. We aimed to determine the incidence of
      intraoperative ureteral injury after laparoscopic and open colectomy and to
      determine the independent morbidity and mortality rates associated with ureteral
      injury. METHODS: We analyzed data from the National Surgical Quality Improvement
      Program for the years 2005-2010. All patients undergoing colectomy for benign,
      neoplastic, or inflammatory conditions were selected. Patients undergoing
      laparoscopic colectomy versus open colectomy were matched on disease severity and
      clinical and demographic characteristics. Multivariate logistic regression
      analyses and coarsened exact matching were used to determine the independent
      difference in the incidence of ureteral injury between the 2 groups. Multivariate
      models were also used to determine the independent association between
      postoperative complications associated with ureteral injury. RESULTS: Of a total
      of 94,526 colectomies, 33,092 (35%) were completed laparoscopically. Ureteral
      injury occurred in a total of 585 patients (0.6%). The crude incidence in the
      open group was higher than that in the laparoscopic group (0.66% versus 0.53%,
      P=.016). CEM produced 14 630 matching pairs. Matched analysis showed the
      likelihood of ureteral injury after laparoscopic colectomy to be 30% less than
      after open colectomy (odds ratio, 0.70; 95% confidence interval, 0.51-0.96).
      Patients with ureteral injury were independently more likely to have septic
      complications and have longer lengths of hospital stay than those without
      ureteral injury. CONCLUSION: Laparoscopic colectomy is associated with a lower
      incidence of intraoperative ureteral injury when compared with open procedures.
      Ureteral injury leads to significant postoperative morbidity even if identified
      and repaired during the colectomy.

PMID- 25392667
TI  - Major vascular injury in laparoscopic urology.
AB  - BACKGROUND AND OBJECTIVES: Major vascular injury is the most devastating
      complication of laparoscopy, occurring most commonly during the laparoscopic
      entry phase. Our goal is to report our experience with major vascular injury
      during laparoscopic entry with closed- and open-access techniques in urologic
      procedures. METHODS: All 5347 patients who underwent laparoscopic urologic
      procedures from 1996 to 2011 at our hospital were included in the study.
      Laparoscopic entry was carried out by either the closed Veress needle technique
      or the modified open Hasson technique. Patients' charts were reviewed
      retrospectively to investigate for access-related major vascular injuries.
      RESULTS: The closed technique was used in the first 474 operations and the open
      technique in the remaining 4873 cases. Three cases of major vascular injury were
      identified among our patients. They were 3 men scheduled for nephrectomy without
      any history of surgery. All injuries occurred in the closed-access group during
      the setup phase with insertion of the first trocar. The injury location was the
      abdominal aorta in 2 patients and the external iliac vein in 1 patient.
      Management was performed after conversion to open surgery, control of bleeding,
      and repair of the injured vessel. CONCLUSIONS: Given the high morbidity and
      mortality rates associated with major vascular injury, its clinically higher
      incidence in laparoscopic urologic procedures with the closed-access technique
      leads us to suggest using the open technique for the entry phase of laparoscopy.
      Using the open-access technique may decrease laparophobia and encourage a higher
      number of urologists to enter the laparoscopy field.

PMID- 25392668
TI  - Laparoscopic appendectomy is safer than open appendectomy in an elderly
      population.
AB  - BACKGROUND AND OBJECTIVES: This study describes perioperative patient safety
      outcomes comparing laparoscopic appendectomy with open appendectomy in the
      elderly population (defined as age>=65 years) during the diffusion of
      laparoscopic appendectomy into widespread clinical practice. METHODS: We
      performed a cross-sectional analysis of patients undergoing open or laparoscopic
      appendectomy in the US Nationwide Inpatient Sample, a 20% sample of inpatient
      discharges from 1056 hospitals, from 1998 to 2009, and used weighted sampling to
      estimate national trends. Multivariate logistic regression modeling was used to
      examine the association of laparoscopy with perioperative outcomes. RESULTS:
      Patients who met the inclusion criteria totaled 257,484. Of these, 87,209 (34%)
      underwent laparoscopic appendectomy. These patients were younger (P<.001); had
      lower Charlson comorbidity scores (P<.001); were more likely to be white
      (P<.001), to be privately insured (P=.005), and to undergo surgery in urban
      hospitals (P<.001); and were less likely to have appendiceal rupture (P<.001).
      Laparoscopic appendectomy was associated with a decreased length of stay (4.44
      days vs 7.86 days, P<.001), fewer total patient safety indicator events (1.8% vs
      3.5%, P<.001), and a decreased mortality rate (0.9% vs 2.8%, P<.001). On
      multivariate analyses, we observed a 32% (odds ratio, 0.68) decreased probability
      of patient safety events occurring in laparoscopic appendectomy cases versus open
      appendectomy cases as measured by patient safety indicators. CONCLUSION: The data
      suggest that laparoscopic appendectomy is associated with improved clinical
      outcomes in the elderly and that diffusion of laparoscopic appendectomy is not
      associated with adverse patient safety events in this population.

PMID- 25392669
TI  - Laparoscopic anterior resection: new anastomosis technique in a pig model.
AB  - BACKGROUND AND OBJECTIVES: Bowel anastomosis after anterior resection is one of
      the most difficult tasks to perform during laparoscopic colorectal surgery. This
      study aims to evaluate a new feasible and safe intracorporeal anastomosis
      technique after laparoscopic left-sided colon or rectum resection in a pig model.
      METHODS: The technique was evaluated in 5 pigs. The OrVil device (Covidien,
      Mansfield, Massachusetts) was inserted into the anus and advanced proximally to
      the rectum. A 0.5-cm incision was made in the sigmoid colon, and the 2 sutures
      attached to its delivery tube were cut. After the delivery tube was evacuated
      through the anus, the tip of the anvil was removed through the perforation. The
      sigmoid colon was transected just distal to the perforation with an endoscopic
      linear stapler. The rectosigmoid segment to be resected was removed through the
      anus with a grasper, and distal transection was performed. A 25-mm circular
      stapler was inserted and combined with the anvil, and end-to-side intracorporeal
      anastomosis was then performed. RESULTS: We performed the technique in 5 pigs.
      Anastomosis required an average of 12 minutes. We observed that the proximal and
      distal donuts were completely removed in all pigs. No anastomotic air leakage was
      observed in any of the animals. CONCLUSION: This study shows the efficacy and
      safety of intracorporeal anastomosis with the OrVil device after laparoscopic
      anterior resection.

PMID- 25392670
TI  - Single-incision laparoscopic splenectomy.
AB  - BACKGROUND AND OBJECTIVES: The single-incision approach in laparoscopic surgery
      is a relatively new concept. This systematic review of the literature was
      performed to appraise the existing clinical evidence concerning the use of the
      single-incision technique for spleen resection. METHODS: We performed a
      systematic search of the PubMed and Scopus databases, and the studies retrieved
      were included in our review. The references of the included studies were also
      hand searched. RESULTS: Thirty-one relevant studies were found in the field
      including 81 patients with an age range from 0.6 to 90 years and a body mass
      index range from 18 to 36.7 kg/m2. Splenomegaly (44.6%), idiopathic
      thrombocytopenic purpura (31%), and immune thrombocytopenic purpura (6.8%) were
      the most common indications for the procedure. Concerning the applied port
      system, multiple single ports (5 to 12 mm) were used in 54.4% of patients, the
      SILS port (Covidien, Mansfield, Massachusetts) was used in 26.6%, the TriPort
      (Advanced Surgical Concepts, Wicklow, Ireland) was used in 7.6%, glove ports were
      used in 6.3%, and the GelPort (Applied Medical, Rancho Santa Margarita,
      California) was used in 5.1%. The median operative time was 125 minutes (range,
      45-420 minutes), and the median quantity of blood loss was 50 mL (range, 10-450
      mL). No conversion to open surgery and no transfusion were needed. The length of
      hospital stay was between 1 and 9 days. Low rates of complications and no patient
      deaths were found. The existing evidence on cosmesis is limited. CONCLUSION:
      Single-site/single-port laparoscopic surgery is a minimally invasive procedure
      that seems to be a challenging alternative in the management of spleen resection.

PMID- 25392672
TI  - "Lapbotic" surgery: blending the expertise of an advanced minimally invasive
      surgeon with the precision of a robot to best serve the patient.

PMID- 25392671
TI  - Prospective randomized comparison between transperitoneal laparoscopic
      pyeloplasty and retroperitoneoscopic pyeloplasty for primary ureteropelvic
      junction obstruction.
AB  - BACKGROUND AND OBJECTIVES: To compare laparoscopic transperitoneal versus
      retroperitoneoscopic pyeloplasty for primary ureteropelvic junction obstruction
      in a prospective randomized manner and assess overall results with long-term
      follow-up. METHODS: In this prospective study, from 2008 to 2012, 112 cases of
      primary ureteropelvic junction obstruction were randomized in a 1:1 ratio into 2
      groups. Group I included patients who underwent transperitoneal laparoscopic
      pyeloplasty, and group II consisted of patients who underwent
      retroperitoneoscopic laparoscopic pyeloplasty. Demographic and clinical
      characteristics and postoperative and operative data were collected and analyzed.
      The statistical analysis was performed with the Fisher exact test, chi2 test, and
      Mann-Whitney U test for independent groups, and P<.05 was considered
      statistically significant. RESULTS: The total operative time and intracorporeal
      suturing time were significantly higher in group II than in group I (P<.001). The
      visual analog scale score for pain on postoperative day 1 and the requirement for
      tramadol were significantly higher in group I than in group II (P=.004). The
      hospital stay and the rate of temporary ileus were significantly greater (P<.036
      and P<.02, respectively) in group I than in group II. The success rate of
      transperitoneal laparoscopic pyeloplasty versus retroperitoneoscopic laparoscopic
      pyeloplasty was 96.4% versus 96.6% with a mean follow-up period of 30.75+/-4.85
      months versus 30.99+/-5.59 months (P<.88). CONCLUSION: Transperitoneal
      laparoscopic pyeloplasty is associated with significantly greater postoperative
      pain, a higher tramadol dose, a higher rate of ileus, and a longer hospital stay
      in comparison with retroperitoneoscopic laparoscopic pyeloplasty. Although the
      operative time for retroperitoneoscopic laparoscopic pyeloplasty is significantly
      longer, the success rate remains the same for both procedures.

PMID- 25392673
TI  - Preoperative change in 6-minute walk distance correlates with early weight loss
      after sleeve gastrectomy.
AB  - INTRODUCTION: The 6-minute walk test (6MWT) is an objective preoperative measure
      of functional capacity and response to intervention in patients with heart or
      lung disease. In bariatric surgery, there has been no reliable preoperative
      measure predictive of postoperative success. Here we investigated the impact of
      bariatric surgery on changes in distance traveled in the 6MWT (the 6MWD) and
      whether preoperative changes in 6MWD correlated with weight change after surgery.
      METHODS: This is a retrospective study of consecutive patients in which the 6MWT
      was performed before and after laparoscopic sleeve gastrectomy for weight loss.
      6MWD and total weight were measured. Pearson correlation was used to determine
      association between variables. RESULTS: Of 100 patients who underwent
      laparoscopic sleeve gastrectomy, 31 patients had a preoperative 6MWT. Thirty
      patients (97%) were available for follow-up after surgery. Percentage of excess
      weight loss was 45.7% over an average of 7 months after surgery. There was a weak
      correlation between the postoperative weight loss and the change in preoperative
      and postoperative 6MWD (r=0.28; P=.13). In a subset of patients who demonstrated
      a change in distance traveled in 2 separate preoperative 6MWD measurements
      (average 18.5% increase in distance), there was a strong correlation with
      postoperative weight loss (r=0.82; P=.02). CONCLUSIONS: A demonstrated increase
      in 6MWD before surgery correlates strongly with early postoperative weight loss
      after laparoscopic sleeve gastrectomy. A multidisciplinary team that includes a
      physical therapist is useful in preparing bariatric patients for surgery.

PMID- 25392674
TI  - Transperitoneal laparoscopic adrenalectomy in children.
AB  - PURPOSE: The use of a minimally invasive approach for adrenalectomy is poorly
      defined in pediatric patients, although laparoscopic adrenalectomy is considered
      a standard procedure in adults. The aim of our study was to describe the safety
      and feasibility of minimally invasive adrenalectomy in children on the basis of
      surgical skills and results. MATERIALS AND METHODS: This was a retrospective
      study of 4 pediatric laparoscopic adrenalectomies performed at our center between
      2009 and 2012. All patients underwent transperitoneal lateral laparoscopic
      adrenalectomies (2 right and 2 left adrenalectomies). RESULTS: Four laparoscopic
      adrenalectomies were performed. Indications for surgery were neuroblastoma in 2
      patients, secernent adrenocortical tumor in 1 patient, and adrenocortical nodular
      hyperplasia in 1 patient. Patients had a mean age of 87 months (range, 17-156
      months) at diagnosis, and the average lesion size was 3.23 cm (range, 0.7-6.4
      cm). All laparoscopic adrenalectomies were successful, no conversions to open
      surgery were required, and no postoperative complications or deaths occurred. The
      average operating time was 105 minutes (range, 80-130 minutes), blood loss during
      surgery was minimal, and the mean postoperative hospital stay was 3.75 days
      (range, 3-5 days). None of the patients showed signs of recurring disease at 15
      month follow-up. CONCLUSIONS: Laparoscopic adrenalectomy is a safe, feasible, and
      reproducible technique offering numerous advantages, including shortening of
      operating times and postoperative hospital stays, as well as reduction of blood
      loss and complications. It also provides good visibility and easy access to other
      organs.

PMID- 25392675
TI  - Effectiveness of gastric neurostimulation in patients with gastroparesis.
AB  - BACKGROUND: Patients with gastroparesis have significantly delayed gastric
      emptying because of impaired nerve function. Gastric neurostimulation from
      Enterra Therapy provides electrical pulses to the stomach tissue that promotes
      stimulation of stomach smooth muscle, thereby enhancing gastric emptying. This
      study evaluates the effectiveness of Enterra Therapy (Medtronic, Minneapolis,
      Minnesota) in reducing symptoms and improving the quality of life of patients
      with drug-refractory gastroparesis. MATERIAL AND METHODS: In this study 25
      patients underwent minimally invasive, laparoscopic placement of the Enterra
      Therapy device. Patients were asked to rank their severity of symptoms and
      quality of life retrospectively by completing the Gastrointestinal Symptoms
      Rating Scale and Short Form 36 Health Survey with respect to their condition
      before and 6 months after initiation of Enterra Therapy. RESULTS: Eighteen
      patients completed the surveys. Patients showed statistically significant
      improvement in their overall Gastrointestinal Symptoms Rating Scale scores and
      the mental health component of the Short Form 36 Health Survey. DISCUSSION:
      Currently, Enterra Therapy has Humanitarian Use Device status, which means that
      more clinical evidence is needed to prove its effectiveness in gastroparesis. By
      showing that Enterra Therapy reduces symptoms of gastroparesis and improves
      patient quality of life, this study contributes to the increasing amount of data
      supporting its use and potential Food and Drug Administration approval.

PMID- 25392676
TI  - Clinical use of a cordless laparoscopic ultrasonic device.
AB  - OBJECTIVE: On April 25, 2012, the first laparoscopic cordless ultrasonic device
      (Sonicision, Covidien, Mansfield, Massachusetts) was used in a clinical setting.
      We describe our initial experience. METHODS: The cordless device is assembled
      with a reusable battery and generator on a base hand-piece. It has a minimum and
      maximum power setting controlled by a single trigger for both coagulation and
      cutting. A laparoscopic radical nephrectomy was performed on a 56-year-old man
      with a 7-cm right renal mass. A laparoscopic pelvic lymphadenectomy was performed
      in a 51-year-old man with high-risk prostate cancer. Data on surgical team
      satisfaction, operative time, number of activations, and times the laparoscope
      was removed as a result of plume were collected. RESULTS: The surgical technician
      successfully assembled the device at the beginning of the cases with verbal
      instructions from the surgeon. Operative time for nephrectomy was 77 minutes,
      with 143 total activations (minimum = 86, maximum = 57). The operative time for
      the pelvic lymphadenectomy was 27 minutes, with 38 total activations (minimum =
      27, maximum = 11). One battery was used in each case. The laparoscope was removed
      twice during the nephrectomy and once during the lymphadenectomy. Surgical staff
      satisfaction survey results revealed easier and faster assembly, more space in
      the operating room, ergonomic handle, and comparable cutting/coagulation, weight,
      and plume generation with other devices (Table 1). [Table: see text]. CONCLUSION:
      The first clinical application of the pioneering cordless dissector was
      successfully performed, resulting in surgeons' perceptions of comparable results
      with other devices of easier and safer use and faster assembly.

PMID- 25392677
TI  - Hospital costs associated with laparoscopic and open inguinal herniorrhaphy.
AB  - PURPOSE: The purpose of this study was to compare the total hospital costs
      associated with elective laparoscopic and open inguinal herniorrhaphy. METHODS: A
      prospectively maintained database was used to identify patients who underwent
      elective inguinal herniorrhaphy from April 2009 to March 2011. A retrospective
      review of electronic patient records was performed along with a standardized case
      costing analysis using data from the Ontario Case Costing Initiative. The main
      outcomes were operating room (OR) and total hospital costs. RESULTS: Two hundred
      eleven patients underwent elective unilateral inguinal herniorrhaphy (117 open
      and 94 laparoscopic), and 33 patients underwent elective bilateral inguinal
      herniorrhaphy (9 open and 24 laparoscopic). OR and total hospital costs for open
      unilateral inguinal hernia repair were significantly lower than for the
      laparoscopic approach (median total cost, $3207.15 vs $3723.66; P < .001). OR and
      total hospital costs for repair of elective bilateral inguinal hernias were
      similar between the open and laparoscopic approaches (median total cost, $4574.02
      vs $4662.89; P = .827). CONCLUSIONS: In the setting of a Canadian academic
      hospital, when considering the repair of an elective unilateral inguinal hernia,
      the OR and total hospital costs of open surgery were significantly lower than for
      the laparoscopic techniques. There was no statistical difference between OR and
      total hospital costs when comparing open surgery and laparoscopic techniques for
      the repair of bilateral inguinal hernias. Given the perioperative benefits of
      laparoscopy, further studies incorporating hernia-specific outcomes are necessary
      to determine the cost-effectiveness of each approach and to define the optimal
      treatment strategy.

PMID- 25392679
TI  - Change-point diagnostics in competing risks models: Two posterior predictive p
      value approaches.
AB  - This paper presents a Bayesian diagnostic procedure for examining change-point
      assumption in the competing risks model framework. It considers the family of
      distributions arising from the cause-specific model as reported by Chiang
      (Introduction to stochastic processes in biostatistics. Wiley, New York, 1968)
      upon which change-points are added to accommodate possible distributional
      heterogeneity. Model departure, due to misspecification of change-points
      associated with either the overall survival distribution or cause-specific
      probabilities, is quantified in terms of a sequence of cumulative-sum statistics
      between each pair of adjacent change-points assumed. When assessing the
      asymptotic behavior of each sequence of cumulative-sum statistics using its
      posterior predictive p-values, see Rubin (Ann Stat 12:1151-1172, 1984) and
      partial posterior predictive p-values as reported by Bayarri and Berger (J Am
      Stat Assoc 95:1127-1142, 2000), we show that both types of p-values attain their
      greatest departure from 0.5 at the change-point that is missed in the assumed
      model, from which a diagnostic procedure is formalized. Statistical power of
      these two types of p-values is discussed.

PMID- 25392678
TI  - Advanced hysteroscopic surgery training.
AB  - Hysteroscopic surgery is pivotal in management of many gynecological pathologies.
      The skills required for performing advanced hysteroscopic surgery (AHS), eg,
      transcervical hysteroscopic endometrial resection (TCRE), hysteroscopic
      polypectomy and myomectomy in the management of menorrhagia, hysteroscopic
      septulysis in fertility-related gynecological problems and hysteroscopic removal
      of chronically retained products of conception and excision of intramural ectopic
      pregnancy ought to be practiced by contemporary gynecological surgeons in their
      day-to-day clinical practice. AHS is a minimally invasive procedure that
      preserves the uterus in most cases. Whilst the outcome is of paramount
      importance, proper training should be adopted and followed through so that
      doctors, nurses, and institutions may deliver the highest standard of patient
      care. 

PMID- 25392680
TI  - Optimization of Network Topology in Computer-Aided Detection Schemes Using Phased
      Searching with NEAT in a Time-Scaled Framework.
AB  - In the field of computer-aided mammographic mass detection, many different
      features and classifiers have been tested. Frequently, the relevant features and
      optimal topology for the artificial neural network (ANN)-based approaches at the
      classification stage are unknown, and thus determined by trial-and-error
      experiments. In this study, we analyzed a classifier that evolves ANNs using
      genetic algorithms (GAs), which combines feature selection with the learning
      task. The classifier named "Phased Searching with NEAT in a Time-Scaled
      Framework" was analyzed using a dataset with 800 malignant and 800 normal tissue
      regions in a 10-fold cross-validation framework. The classification performance
      measured by the area under a receiver operating characteristic (ROC) curve was
      0.856 +/- 0.029. The result was also compared with four other well-established
      classifiers that include fixed-topology ANNs, support vector machines (SVMs),
      linear discriminant analysis (LDA), and bagged decision trees. The results show
      that Phased Searching outperformed the LDA and bagged decision tree classifiers,
      and was only significantly outperformed by SVM. Furthermore, the Phased Searching
      method required fewer features and discarded superfluous structure or topology,
      thus incurring a lower feature computational and training and validation time
      requirement. Analyses performed on the network complexities evolved by Phased
      Searching indicate that it can evolve optimal network topologies based on its
      complexification and simplification parameter selection process. From the
      results, the study also concluded that the three classifiers - SVM, fixed
      topology ANN, and Phased Searching with NeuroEvolution of Augmenting Topologies
      (NEAT) in a Time-Scaled Framework - are performing comparably well in our
      mammographic mass detection scheme. 

PMID- 25392681
TI  - Inferring Aberrant Signal Transduction Pathways in Ovarian Cancer from TCGA Data.
AB  - This paper concerns a new method for identifying aberrant signal transduction
      pathways (STPs) in cancer using case/control gene expression-level datasets, and
      applying that method and an existing method to an ovarian carcinoma dataset. Both
      methods identify STPs that are plausibly linked to all cancers based on current
      knowledge. Thus, the paper is most appropriate for the cancer informatics
      community. Our hypothesis is that STPs that are altered in tumorous tissue can be
      identified by applying a new Bayesian network (BN)-based method (causal analysis
      of STP aberration (CASA)) and an existing method (signaling pathway impact
      analysis (SPIA)) to the cancer genome atlas (TCGA) gene expression-level
      datasets. To test this hypothesis, we analyzed 20 cancer-related STPs and 6
      randomly chosen STPs using the 591 cases in the TCGA ovarian carcinoma dataset,
      and the 102 controls in all 5 TCGA cancer datasets. We identified all the genes
      related to each of the 26 pathways, and developed separate gene expression
      datasets for each pathway. The results of the two methods were highly correlated.
      Furthermore, many of the STPs that ranked highest according to both methods are
      plausibly linked to all cancers based on current knowledge. Finally, CASA ranked
      the cancer-related STPs over the randomly selected STPs at a significance level
      below 0.05 (P = 0.047), but SPIA did not (P = 0.083). 

PMID- 25392682
TI  - Mining cancer-specific disease comorbidities from a large observational health
      database.
AB  - Cancer comorbidities often reflect the complex pathogenesis of cancers and
      provide valuable clues to discover the underlying genetic mechanisms of cancers.
      In this study, we systematically mine and analyze cancer-specific comorbidity
      from the FDA Adverse Event Reporting System. We stratified 3,354,043 patients
      based on age and gender, and developed a network-based approach to extract
      comorbidity patterns from each patient group. We compared the comorbidity
      patterns among different patient groups and investigated the effect of age and
      gender on cancer comorbidity patterns. The results demonstrated that the
      comorbidity relationships between cancers and non-cancer diseases largely depend
      on age and gender. A few exceptions are depression, anxiety, and metabolic
      syndrome, whose comorbidity relationships with cancers are relatively stable
      among all patients. Literature evidences demonstrate that these stable cancer
      comorbidities reflect the pathogenesis of cancers. We applied our comorbidity
      mining approach on colorectal cancer and detected its comorbid associations with
      metabolic syndrome components, diabetes, and osteoporosis. Our results not only
      confirmed known cancer comorbidities but also generated novel hypotheses, which
      can illuminate the common pathophysiology between cancers and their co-occurring
      diseases. 

PMID- 25392683
TI  - Feasibility and implementation of a literature information management system for
      human papillomavirus in head and neck cancers with imaging.
AB  - This work examines the feasibility and implementation of information service
      orientated architecture (ISOA) on an emergent literature domain of human
      papillomavirus, head and neck cancer, and imaging. From this work, we examine the
      impact of cancer informatics and generate a full set of summarizing clinical
      pearls. Additionally, we describe how such an ISOA creates potential benefits in
      informatics education, enhancing utility for creating enduring digital content in
      this clinical domain. 

PMID- 25392684
TI  - Modeling signal transduction from protein phosphorylation to gene expression.
AB  - BACKGROUND: Signaling networks are of great importance for us to understand the
      cell's regulatory mechanism. The rise of large-scale genomic and proteomic data,
      and prior biological knowledge has paved the way for the reconstruction and
      discovery of novel signaling pathways in a data-driven manner. In this study, we
      investigate computational methods that integrate proteomics and transcriptomic
      data to identify signaling pathways transmitting signals in response to specific
      stimuli. Such methods can be applied to cancer genomic data to infer perturbed
      signaling pathways. METHOD: We proposed a novel Bayesian Network (BN) framework
      to integrate transcriptomic data with proteomic data reflecting protein
      phosphorylation states for the purpose of identifying the pathways transmitting
      the signal of diverse stimuli in rat and human cells. We represented the proteins
      and genes as nodes in a BN in which edges reflect the regulatory relationship
      between signaling proteins. We designed an efficient inference algorithm that
      incorporated the prior knowledge of pathways and searched for a network structure
      in a data-driven manner. RESULTS: We applied our method to infer rat and human
      specific networks given gene expression and proteomic datasets. We were able to
      effectively identify sparse signaling networks that modeled the observed
      transcriptomic and proteomic data. Our methods were able to identify distinct
      signaling pathways for rat and human cells in a data-driven manner, based on the
      facts that rat and human cells exhibited distinct transcriptomic and proteomics
      responses to a common set of stimuli. Our model performed well in the SBV
      IMPROVER challenge in comparison to other models addressing the same task. The
      capability of inferring signaling pathways in a data-driven fashion may
      contribute to cancer research by identifying distinct aberrations in signaling
      pathways underlying heterogeneous cancers subtypes.

PMID- 25392686
TI  - Disease Biomarker Query from RNA-Seq Data.
AB  - As a revolutionary way to unveil transcription, RNA-Seq technologies are
      challenging bioinformatics for its large data volumes and complexities. A large
      number of computational models have been proposed for differential expression
      (DE) analysis and normalization from different standing points. However, there
      were no studies available yet to conduct disease biomarker discovery for this
      type of high-resolution digital gene expression data, which will actually be
      essential to explore its potential in clinical bioinformatics. Although there
      were many biomarker discovery algorithms available in traditional omics
      communities, they cannot be applied to RNA-Seq count data to seek biomarkers
      directly for its special characteristics. In this work, we have presented a
      biomarker discovery algorithm, SEQ-Marker for RNA-Seq data, which is built on a
      novel data-driven feature selection algorithm, nonnegative singular value
      approximation (NSVA), which contributes to the robustness and sensitivity of the
      following DE analysis by taking advantages of the built-in characteristics of RNA
      Seq count data. As a biomarker discovery algorithm built on network marker
      topology, the proposed SEQ-Marker not only bridges transcriptomics and systems
      biology but also contributes to clinical diagnostics. 

PMID- 25392685
TI  - Text mining in cancer gene and pathway prioritization.
AB  - Prioritization of cancer implicated genes has received growing attention as an
      effective way to reduce wet lab cost by computational analysis that ranks
      candidate genes according to the likelihood that experimental verifications will
      succeed. A multitude of gene prioritization tools have been developed, each
      integrating different data sources covering gene sequences, differential
      expressions, function annotations, gene regulations, protein domains, protein
      interactions, and pathways. This review places existing gene prioritization tools
      against the backdrop of an integrative Omic hierarchy view toward cancer and
      focuses on the analysis of their text mining components. We explain the
      relatively slow progress of text mining in gene prioritization, identify several
      challenges to current text mining methods, and highlight a few directions where
      more effective text mining algorithms may improve the overall prioritization task
      and where prioritizing the pathways may be more desirable than prioritizing only
      genes. 

PMID- 25392687
TI  - Prediction of MicroRNA Precursors Using Parsimonious Feature Sets.
AB  - MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate gene
      expression through base pairing with messenger RNAs. Due to the interest in
      studying miRNA dysregulation in disease and limits of validated miRNA references,
      identification of novel miRNAs is a critical task. The performance of different
      models to predict novel miRNAs varies with the features chosen as predictors.
      However, no study has systematically compared published feature sets. We
      constructed a comprehensive feature set using the minimum free energy of the
      secondary structure of precursor miRNAs, a set of nucleotide-structure triplets,
      and additional extracted sequence and structure characteristics. We then compared
      the predictive value of our comprehensive feature set to those from three
      previously published studies, using logistic regression and random forest
      classifiers. We found that classifiers containing as few as seven highly
      predictive features are able to predict novel precursor miRNAs as well as
      classifiers that use larger feature sets. In a real data set, our method
      correctly identified the holdout miRNAs relevant to renal cancer. 

PMID- 25392688
TI  - Exploiting Literature-derived Knowledge and Semantics to Identify Potential
      Prostate Cancer Drugs.
AB  - In this study, we report on the performance of an automated approach to discovery
      of potential prostate cancer drugs from the biomedical literature. We used the
      semantic relationships in SemMedDB, a database of structured knowledge extracted
      from all MEDLINE citations using SemRep, to extract potential relationships using
      knowledge of cancer drugs pathways. Two cancer drugs pathway schemas were
      constructed using these relationships extracted from SemMedDB. Through both
      pathway schemas, we found drugs already used for prostate cancer therapy and
      drugs not currently listed as the prostate cancer medications. Our study
      demonstrates that the appropriate linking of relevant structured semantic
      relationships stored in SemMedDB can support the discovery of potential prostate
      cancer drugs. 

PMID- 25392689
TI  - Inferring the Effects of Honokiol on the Notch Signaling Pathway in SW480 Colon
      Cancer Cells.
AB  - In a tumor cell, the development of acquired therapeutic resistance and the
      ability to survive in extracellular environments that differ from the primary
      site are the result of molecular adaptations in potentially highly plastic
      molecular networks. The accurate prediction of intracellular networks in a tumor
      remains a difficult problem in cancer informatics. In order to make truly
      rational patient-driven therapeutic decisions, it will be critical to develop
      methodologies that can accurately infer the molecular circuitry in the cells of a
      specific tumor. Despite enormous heterogeneity, cellular networks elicit
      deterministic digital-like responses. We discuss the use and limitations of
      methodologies that model molecular networks in cancer cells as a digital circuit.
      We also develop a network model of Notch signaling in colon cancer using a novel
      reverse engineering logic-based method and published western blot data to
      elucidate the interactions likely present in the circuits of the SW480 colon
      cancer cell line. Within this framework, we make predictions related to the role
      that honokiol may be playing as an anti-cancer drug. 

PMID- 25392690
TI  - Integrated DNA Copy Number and Gene Expression Regulatory Network Analysis of Non
      small Cell Lung Cancer Metastasis.
AB  - Integrative analysis of multi-level molecular profiles can distinguish
      interactions that cannot be revealed based on one kind of data in the analysis of
      cancer susceptibility and metastasis. DNA copy number variations (CNVs) are
      common in cancer cells, and their role in cell behaviors and relationship to gene
      expression (GE) is poorly understood. An integrative analysis of CNV and genome
      wide mRNA expression can discover copy number alterations and their possible
      regulatory effects on GE. This study presents a novel framework to identify
      important genes and construct potential regulatory networks based on these genes.
      Using this approach, DNA copy number aberrations and their effects on GE in lung
      cancer progression were revealed. Specifically, this approach contains the
      following steps: (1) select a pool of candidate driver genes, which have
      significant CNV in lung cancer patient tumors or have a significant association
      with the clinical outcome at the transcriptional level; (2) rank important driver
      genes in lung cancer patients with good prognosis and poor prognosis,
      respectively, and use top-ranked driver genes to construct regulatory networks
      with the COpy Number and EXpression In Cancer (CONEXIC) method; (3) identify
      experimentally confirmed molecular interactions in the constructed regulatory
      networks using Ingenuity Pathway Analysis (IPA); and (4) visualize the refined
      regulatory networks with the software package Genatomy. The constructed CNV/mRNA
      regulatory networks provide important insights into potential CNV-regulated
      transcriptional mechanisms in lung cancer metastasis. 

PMID- 25392691
TI  - Profiling the microRNA Expression in Human iPS and iPS-derived Retinal Pigment
      Epithelium.
AB  - The purpose of this study is to characterize the microRNA (miRNA) expression
      profiles of induced pluripotent stem (iPS) cells and retinal pigment epithelium
      (RPE) derived from induced pluripotent stem cells (iPS-RPE). MiRNAs have been
      demonstrated to play critical roles in both maintaining pluripotency and
      facilitating differentiation. Gene expression networks accountable for
      maintenance and induction of pluripotency are linked and share components with
      those networks implicated in oncogenesis. Therefore, we hypothesize that miRNA
      expression profiling will distinguish iPS cells from their iPS-RPE progeny. To
      identify and analyze differentially expressed miRNAs, RPE was derived from iPS
      using a spontaneous differentiation method. MiRNA microarray analysis identified
      155 probes that were statistically differentially expressed between iPS and iPS
      RPE cells. Up-regulated miRNAs including miR-181c and miR-129-5p may play a role
      in promoting differentiation, while down-regulated miRNAs such as miR-367, miR
      18b, and miR-20b are implicated in cell proliferation. Subsequent miRNA-target
      and network analysis revealed that these miRNAs are involved in cellular
      development, cell cycle progression, cell death, and survival. A systematic
      interrogation of temporal and spatial expression of iPS-RPE miRNAs and their
      associated target mRNAs will provide new insights into the molecular mechanisms
      of carcinogenesis, eye differentiation and development. 

PMID- 25392693
TI  - Co-expression Network Analysis of Human lncRNAs and Cancer Genes.
AB  - We used gene co-expression network analysis to functionally annotate long
      noncoding RNAs (lncRNAs) and identify their potential cancer associations. The
      integrated microarray data set from our previous study was used to extract the
      expression profiles of 1,865 lncRNAs. Known cancer genes were compiled from the
      Catalogue of Somatic Mutations in Cancer and UniProt databases. Co-expression
      analysis identified a list of previously uncharacterized lncRNAs that showed
      significant correlation in expression with core cancer genes. To further annotate
      the lncRNAs, we performed a weighted gene co-expression network analysis, which
      resulted in 37 co-expression modules. Three biologically interesting modules were
      analyzed in depth. Two of the modules showed relatively high expression in blood
      and brain tissues, whereas the third module was found to be downregulated in
      blood cells. Hub lncRNA genes and enriched functional annotation terms were
      identified within the modules. The results suggest the utility of this approach
      as well as potential roles of uncharacterized lncRNAs in leukemia and
      neuroblastoma. 

PMID- 25392692
TI  - Network-based identification of biomarkers coexpressed with multiple pathways.
AB  - Unraveling complex molecular interactions and networks and incorporating clinical
      information in modeling will present a paradigm shift in molecular medicine.
      Embedding biological relevance via modeling molecular networks and pathways has
      become increasingly important for biomarker identification in cancer
      susceptibility and metastasis studies. Here, we give a comprehensive overview of
      computational methods used for biomarker identification, and provide a
      performance comparison of several network models used in studies of cancer
      susceptibility, disease progression, and prognostication. Specifically, we
      evaluated implication networks, Boolean networks, Bayesian networks, and
      Pearson's correlation networks in constructing gene coexpression networks for
      identifying lung cancer diagnostic and prognostic biomarkers. The results show
      that implication networks, implemented in Genet package, identified sets of
      biomarkers that generated an accurate prediction of lung cancer risk and
      metastases; meanwhile, implication networks revealed more biologically relevant
      molecular interactions than Boolean networks, Bayesian networks, and Pearson's
      correlation networks when evaluated with MSigDB database. 

PMID- 25392694
TI  - Learning dysregulated pathways in cancers from differential variability analysis.
AB  - Analysis of gene sets can implicate activity in signaling pathways that is
      responsible for cancer initiation and progression, but is not discernible from
      the analysis of individual genes. Multiple methods and software packages have
      been developed to infer pathway activity from expression measurements for set of
      genes targeted by that pathway. Broadly, three major methodologies have been
      proposed: over-representation, enrichment, and differential variability. Both
      over-representation and enrichment analyses are effective techniques to infer
      differentially regulated pathways from gene sets with relatively consistent
      differentially expressed (DE) genes. Specifically, these algorithms aggregate
      statistics from each gene in the pathway. However, they overlook multivariate
      patterns related to gene interactions and variations in expression. Therefore,
      the analysis of differential variability of multigene expression patterns can be
      essential to pathway inference in cancers. The corresponding methodologies and
      software packages for such multivariate variability analysis of pathways are
      reviewed here. We also introduce a new, computationally efficient algorithm,
      expression variation analysis (EVA), which has been implemented along with a
      previously proposed algorithm, Differential Rank Conservation (DIRAC), in an open
      source R package, gene set regulation (GSReg). EVA inferred similar pathways as
      DIRAC at reduced computational costs. Moreover, EVA also inferred different
      dysregulated pathways than those identified by enrichment analysis. 

PMID- 25392695
TI  - Predicting cancer prognosis using functional genomics data sets.
AB  - Elucidating the molecular basis of human cancers is an extremely complex and
      challenging task. A wide variety of computational tools and experimental
      techniques have been used to address different aspects of this characterization.
      One major hurdle faced by both clinicians and researchers has been to pinpoint
      the mechanistic basis underlying a wide range of prognostic outcomes for the same
      type of cancer. Here, we provide an overview of various computational methods
      that have leveraged different functional genomics data sets to identify molecular
      signatures that can be used to predict prognostic outcome for various human
      cancers. Furthermore, we outline challenges that remain and future directions
      that may be explored to address them. 

PMID- 25392696
TI  - A Novel Subset of Human Tumors That Simultaneously Overexpress Multiple E2F
      responsive Genes Found in Breast, Ovarian, and Prostate Cancers.
AB  - Reasoning that overexpression of multiple E2F-responsive genes might be a useful
      marker for RB1 dysfunction, we compiled a list of E2F-responsive genes from the
      literature and evaluated their expression in publicly available gene expression
      microarray data of patients with breast cancer, serous ovarian cancer, and
      prostate cancer. In breast cancer, a group of tumors was identified, each of
      which simultaneously overexpressed multiple E2F-responsive genes. Seventy percent
      of these genes were concerned with cell cycle progression, DNA repair, or
      mitosis. These E2F-responsive gene overexpressing (ERGO) tumors frequently
      exhibited additional evidence of Rb/E2F axis dysfunction, were mostly triple
      negative, and preferentially overexpressed multiple basal cytokeratins,
      suggesting that they overlapped substantially with the basal-like tumor subset.
      ERGO tumors were also identified in serous ovarian cancer and prostate cancer. In
      these cancer types, there was no evidence for a tumor subset comparable to the
      breast cancer basal-like subset. A core group of about 30 E2F-responsive genes
      were overexpressed in all three cancer types. Thus, it appears that disorders of
      the Rb/E2F axis can arise at multiple organ sites and produce tumors that
      simultaneously overexpress multiple E2F-responsive genes. 

PMID- 25392697
TI  - Volitional Weight-Lifting in Rats Promotes Adaptation via Performance and Muscle
      Morphology prior to Gains in Muscle Mass.
AB  - Investigation of volitional animal models of resistance training has been
      instrumental in our understanding of adaptive training. However, these studies
      have lacked reactive force measurements, a precise performance measure, and
      morphological analysis at a distinct phase of training - when initial strength
      gains precede muscle hypertrophy. Our aim was to expose rats to one month of
      training (70 or 700 g load) on a custom-designed weight-lifting apparatus for
      analysis of reactive forces and muscle morphology prior to muscle hypertrophy.
      Exclusively following 700 g load training, forces increased by 21% whereas muscle
      masses remained unaltered. For soleus (SOL) and tibialis anterior (TA) muscles,
      700 g load training increased muscle fiber number per unit area by ~20% and
      decreased muscle fiber area by ~20%. Additionally, number of muscle fibers per
      section increased by 18% for SOL muscles. These results establish that distinct
      morphological alterations accompany early strength gains in a volitional animal
      model of load-dependent adaptive resistance training. 

PMID- 25392698
TI  - Evaluation of the Pulmonary Toxicity of a Fume Generated from a Nickel-, Copper
      Based Electrode to be Used as a Substitute in Stainless Steel Welding.
AB  - Epidemiology has indicated a possible increase in lung cancer among stainless
      steel welders. Chromium (Cr) is a primary component of stainless steel welding
      fume. There is an initiative to develop alternative welding consumables [nickel
      (Ni)- and copper (Cu)-based alloys] that do not contain Cr. No study has been
      performed to evaluate the toxicity of fumes generated from Ni- and Cu-based
      consumables. Dose-response and time-course effects on lung toxicity of a Ni- and
      Cu-based welding fume (Ni-Cu WF) were examined using an in vivo and in vitro
      bioassay, and compared with two other well-characterized welding fumes. Even
      though only trace amounts of Cr were present, a persistent increase in lung
      injury and inflammation was observed for the Ni-Cu WF compared to the other
      fumes. The difference in response appears to be due to a direct cytotoxic effect
      by the Ni-Cu WF sample on lung macrophages as opposed to an elevated production
      of reactive oxygen species (ROS). 

PMID- 25392699
TI  - Identification of larvicide-resistant catch basins from three years of larvicide
      trials in a suburb of chicago, IL.
AB  - The tens of thousands of catch basins found in many urban areas are a primary
      target of local vector control agencies for seasonal application of extended
      release larvicides. A concern with using larvicides in these structures is that
      active ingredients can be hampered by high flows, debris, and sediment, all of
      which are common to these structures. As such a certain proportion of basins may
      be "resistant" to larvicide treatments due to site specific characteristics that
      may promote these and other factors that hinder larvicide action and/or promote
      mosquito infestation. Analyses from three years of larvicide efficacy trials
      suggest that over a quarter of basins in the study area may not be receiving
      adequate protection from a single dose of larvicide that is routinely applied.
      Implications of increasing the dose and/or toxicity of larvicide treatments are
      discussed further. 

PMID- 25392700
TI  - Impact of d-Dimers on the Differential Diagnosis of Acute Chest Pain: Current
      Aspects Besides the Widely Known.
AB  - d-dimers are cleavage products of fibrin that occur during plasmin-mediated
      fibrinolysis of blood clots. In the emergency department, d-dimer measurement
      represents a valuable and cost-effective tool in the differential diagnosis of
      acute chest pain including the main life-threatening entities: acute coronary
      syndrome, pulmonary embolism, and acute aortic syndrome. Whereas the diagnostic
      and prognostic values of d-dimer testing in acute coronary syndrome is of less
      priority, increases of d-dimers are frequently found in venous thromboembolism
      and acute aortic syndromes, especially acute aortic dissection. As to the high
      negative predictive value of d-dimer in those disorders, patients with low to
      intermediate pretest probability may profit in terms of less necessity of further
      non-invasive or even invasive imaging, simultaneously reducing potential
      complications and healthcare-related costs. However, because of the low
      specificity of the different d-dimer tests in contrast to its frequent usage,
      adequate interpretation is required. Age-related adjustment of d-dimer levels may
      be used to increase its diagnostic power. 

PMID- 25392701
TI  - Unusual Case of a Free-floating Ball Thrombus with Preserved Attachment to the
      Left Atrial Appendage Causing Recurrent Obstruction of the Left Ventricular
      Outflow Tract.
AB  - Few cases of a left atrial thrombus without mitral valve disease have been
      reported. We present an unusual case in which a patient presented to the
      emergency department with syncope and acute cerebral ischemia caused by a ball
      thrombus originating from the left atrium (LA). An emergency bedside
      echocardiogram showed the LA ball thrombus intermittently obstructing the mitral
      orifice and, at times, compromising the left ventricular outflow tract. This
      thrombus was determined to be the source of cerebral embolization resulting in
      acute ischemia. Surgical excision of the mass was performed. At operation, the
      thrombus was found to be tethered to the left atrial appendage. This tethering
      was not apparent on the echocardiographic images, where the thrombus appeared to
      be free floating. This case demonstrates the utility of transthoracic
      echocardiography in establishing the etiology of emergent conditions seemingly
      unrelated to acute cardiac disease, in this situation a neurologic presentation
      with syncope and cerebral ischemia. 

PMID- 25392702
TI  - PET-directed, 3D Ultrasound-guided prostate biopsy.
AB  - Multimodatity imaging is a promising approach for improving prostate cancer
      detection and diagnosis. This article describes various concepts in PET-directed,
      ultrasound-guided biopsies and highlights a new PET/ultrasound fusion targeted
      biopsy system for prostate cancer detection.

PMID- 25392704
TI  - Exact Covariance Thresholding into Connected Components for Large-Scale Graphical
      Lasso.
AB  - We consider the sparse inverse covariance regularization problem or graphical
      lasso with regularization parameter lambda. Suppose the sample covariance graph
      formed by thresholding the entries of the sample covariance matrix at lambda is
      decomposed into connected components. We show that the vertex-partition induced
      by the connected components of the thresholded sample covariance graph (at
      lambda) is exactly equal to that induced by the connected components of the
      estimated concentration graph, obtained by solving the graphical lasso problem
      for the same lambda. This characterizes a very interesting property of a path of
      graphical lasso solutions. Furthermore, this simple rule, when used as a wrapper
      around existing algorithms for the graphical lasso, leads to enormous performance
      gains. For a range of values of lambda, our proposal splits a large graphical
      lasso problem into smaller tractable problems, making it possible to solve an
      otherwise infeasible large-scale problem. We illustrate the graceful scalability
      of our proposal via synthetic and real-life microarray examples.

PMID- 25392703
TI  - COMPARISON OF BASELINE DRINKING PRACTICES, KNOWLEDGE, AND ATTITUDES OF ADULTS
      RESIDING IN COMMUNITIES TAKING PART IN THE FAS PREVENTION STUDY IN SOUTH AFRICA.
AB  - Foetal Alcohol Syndrome (FAS) has been identified as among the most serious
      consequences associated with hazardous and harmful drinking in the Western Cape
      province, South Africa. Community surveys were conducted in two wine growing
      regions in this province to assess drinking behaviour, guide interventions and
      serve as a baseline for assessing the impact of population-level interventions.
      As part of a cross-sectional comparative study interviews were conducted with 384
      and 209 randomly selected adults in the prevention (PC) and comparison
      communities (CC) respectively. Over 80% of respondents resided in urban areas,
      except in the CC, where 61% of males resided on farms. Symptoms of hazardous or
      harmful drinking were reported by 16.0% of females and 32.5% of males in the PC,
      while 19.3% of females and 56.2% of males in the CC reported such drinking. Over
      two-thirds of respondents indicated that it was equally harmful for a woman to
      drink during any of the trimesters of pregnancy, but more than 30% of the women
      interviewed had never had a health worker speak to them about the effects of
      drinking during pregnancy. Over 10% had never heard of fetal alcohol syndrome.
      The findings reinforce the need for interventions to address hazardous/harmful
      use of alcohol in both communities and also to address gaps in knowledge
      regarding the effects of drinking during pregnancy.

PMID- 25392705
TI  - Certificates of Confidentiality: Protecting Human Subject Research Data in Law
      and Practice.
AB  - Researchers often require and collect sensitive information about individuals to
      answer important scientific questions that impact individual health and well
      being and the public health. Researchers recognize they have a duty to maintain
      the confidentiality of the data they collect and typically make promises, which
      are documented in the consent form. The legal interests of others, however, can
      threaten researchers' promises of confidentiality, if they seek access to the
      data through subpoena. Certificates of Confidentiality (Certificates), authorized
      by federal statute, are an important tool for protecting individually
      identifiable sensitive research data from compelled disclosure. However,
      questions persist in the research community about the strength of Certificate
      protections, and the evidence on which to judge the strength is scant. In this
      article, we address those questions through a careful examination of the
      legislation and regulations concerning Certificates and the reported and
      unreported cases we have identified through our legal research and interviews
      with legal counsel about their experiences with Certificates. We also analyze
      other statutes that protect research data to compare them to the Certificate's
      protections, and we review other legal strategies available for protecting
      research data. Based on our analysis, we conclude with recommendations for how to
      strengthen protection of sensitive research data.

PMID- 25392706
TI  - Influence of patterned sapphire substrates with different symmetry on the light
      output power of InGaN-based LEDs.
AB  - This paper aims to investigate the light output power (LOP) of InGaN-based light
      emitting diodes (LEDs) grown on patterned sapphire substrates (PSSs) with
      different symmetry. The GaN epitaxial layers grown on the hexagonal lattice
      arrangement PSS (HLAPSS) have a lower compressive strain than the ones grown on
      the square lattice arrangement PSS (SLAPSS). The quantum-confined Stark effect
      (QCSE) is also affected by the residual compressive strain. Based on the
      experimentally measured data and the ray tracing simulation results, the InGaN
      based LED with the HLAPSS has a higher LOP than the one with the SLAPSS due to
      the weaker QCSE within multiple-quantum wells (MQWs). 

PMID- 25392707
TI  - Controlling the morphological, structural, and optical properties of one
      dimensional PCDTBT nanotubes by template wetting.
AB  - In this study, the synthesis of poly [N-9'-heptadecanyl-2, 7-carbazole-alt-5, 5
      (4', 7'-di-2-thienyl-2', 1', 3'-benzothiadiazole)] (PCDTBT) nanotubes via a
      templating method is reported. PCDTBT nanotubes were successfully grown by
      immersing the porous alumina template into 15 mg/ml of solution concentration for
      2- and 24-h periods and annealed at 50 degrees C. Changes in morphological and
      optical properties between nanotubes of different infiltration times (2 and 24 h)
      as well as its thin films are observed. The longer infiltration time of 24 h
      produced nanotubes with enhanced morphological, structural, and optical
      properties. Nanotubes that are formed between 2 and 24 h of infiltration show
      enhancement in absorption, photoluminescence, and shift in Raman peak if compared
      to their thin films. 

PMID- 25392708
TI  - Ultrafast synthesis of Au(I)-dodecanethiolate nanotubes for advanced Hg(2+)
      sensor electrodes.
AB  - In this work, an ultrafast and facile method is developed to synthesize Au(I)
      dodecanethiolate nanotubes (Au(I)NTs) with the assistance of glycyl-glycyl
      glycine (G-G-G). Transmission electron microscopy (TEM) images reveal that the as
      prepared Au(I)NTs can be obtained in a 2-h reaction instead of a previous 24-h
      reaction and are uniform with a hollow structure and smooth surface by virtue of
      the G-G-G peptide tubular template. According to structural analysis, a possible
      preparative mechanism is proposed that the G-G-G peptide could help to curl into
      tube-like morphology in alkaline situation spontaneously to accelerate the
      formation of Au(I)NTs. Meanwhile, PVDF-stabilized Au(I)NT-modified glassy carbon
      electrodes present their promising potential for Hg(2+) detection. 

PMID- 25392709
TI  - Assessment of the influence of the patient's inflammatory state on the accuracy
      of a haptoglobin selected reaction monitoring assay.
AB  - BACKGROUND: The use of targeted LC-MS/MS methods for protein quantitation in
      clinical laboratories implies a careful evaluation of potential sources of
      analytical interference. In this study, we investigated whether inflammation,
      which is associated with both the release of proteolytic enzymes and increased
      expression of acute phase protease inhibitors, is affecting the accuracy of a
      haptoglobin selected reaction monitoring (SRM) assay. RESULTS: A SRM assay was
      developed and used to quantify haptoglobin in 57 human serum samples. The SRM
      assay had CVs (n = 6) of 12.9% at 698 mg/L and 11.8% at 1690 mg/L. Results of the
      SRM assay were compared to those of a commercial immunonephelometric test.
      Passing-Bablok regression gave a proportional bias of 0.92 (95% CI: 0.82 to 1.04)
      and a constant bias of 75.40 (95% CI: -71.09 to 251.04), indicating that SRM and
      immunonephelometric assays provided comparable results. We then investigated
      whether the accuracy of the SRM assay was influenced by the patient's
      inflammatory state by assessing the relationship between the serum CRP
      concentration and the bias between the two methods. No correlation was found
      between the SRM/immunoassay bias and the CRP concentration (Pearson correlation
      coefficient r = 0.0898). CONCLUSIONS: These data indicate that neither the
      release of proteolytic enzymes nor the increased level of protease inhibitors
      occurring during inflammation processes have a significant impact on the
      haptoglobin SRM assay accuracy. Such studies provide important information about
      potential sources of analytical interferences in protein SRM assays.

PMID- 25392711
TI  - Optical properties of quantum-dot-doped liquid scintillators.
AB  - Semiconductor nanoparticles (quantum dots) were studied in the context of liquid
      scintillator development for upcoming neutrino experiments. The unique optical
      and chemical properties of quantum dots are particularly promising for the use in
      neutrinoless double-beta decay experiments. Liquid scintillators for large scale
      neutrino detectors have to meet specific requirements which are reviewed,
      highlighting the peculiarities of quantum-dot-doping. In this paper, we report
      results on laboratory-scale measurements of the attenuation length and the
      fluorescence properties of three commercial quantum dot samples. The results
      include absorbance and emission stability measurements, improvement in
      transparency due to filtering of the quantum dot samples, precipitation tests to
      isolate the quantum dots from solution and energy transfer studies with quantum
      dots and the fluorophore PPO.

PMID- 25392710
TI  - Protein energy malnutrition increases arginase activity in monocytes and
      macrophages.
AB  - BACKGROUND: Protein energy malnutrition is commonly associated with immune
      dysfunctions and is a major factor in susceptibility to infectious diseases.
      METHODS: In this study, we evaluated the impact of protein energy malnutrition on
      the capacity of monocytes and macrophages to upregulate arginase, an enzyme
      associated with immunosuppression and increased pathogen replication. RESULTS:
      Our results show that monocytes and macrophages are significantly increased in
      the bone marrow and blood of mice fed on a protein low diet. No alteration in the
      capacity of bone marrow derived macrophages isolated from malnourished mice to
      phagocytose particles, to produce the microbicidal molecule nitric oxide and to
      kill intracellular Leishmania parasites was detected. However, macrophages and
      monocytes from malnourished mice express significantly more arginase both in
      vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show
      that following protein energy malnutrition, the increased parasite burden
      measured in the spleen of these mice coincided with increased arginase activity
      and that macrophages provide a more permissive environment for parasite growth.
      CONCLUSIONS: Taken together, these results identify a novel mechanism in protein
      energy malnutrition that might contributes to increased susceptibility to
      infectious diseases by upregulating arginase activity in myeloid cells.

PMID- 25392712
TI  - Importance of halide involving interactions at Hoogsteen sites in supramolecular
      architectures of some coordination metal complexes of N(6)-benzyl/furfuryl
      adenine.
AB  - BACKGROUND: Most of the benzyladenine and furfuryladenine derivatives inhibit
      tumor/cancer cell growth; their toxicity is lesser than the compounds used for
      the treatment of cancer now-a-days. Many cytokinin derivatives are tested for
      anticancer activity. RESULTS: A series of transition metal complexes containing
      N(6)-benzyl/furfuryl aminopurines of formula [Mn(FAH)2(H2O)(Cl3)]2.Cl2 (1),
      [Co(FAH)2(H2O)(Cl3)]2.Cl2 (2), [Co(FAH)2(Cl4)]2 .[Co(FAH)2(H3O)(Cl3)].Cl2 (3),
      [Ni(FAH)2(H2O)(Cl3)]2.Cl2. (H2O) (4), [Zn(BAH)Br3] (5) and [Cd2(BAH)2(MU
      Br)4Br2]n (6) (where BAH and FAH benzyladeninium and furfuryladeninium cations
      respectively) have been synthesized and characterized. Crystal structures of (1
      4) have similar distorted octahedral coordination geometry, while (5) and (6)
      have distorted tetrahedral geometry and octahedral geometries respectively. In (1
      4) two halide ions and two cytokinin cations (BAH(+)/FAH(+)) are laterally
      coordinated to the metal ion. A water molecule and a halide ion are axially
      coordinated. But the coordination sphere of (5) consists of N7 coordinated
      benzyladeninium ion and three halide ions. The complex (6) is a coordination
      polymer bridged by bromide anions. A common notable feature in (1-4) is the
      presence of one or more lattice chloride anions. They help in a chain formation
      by N-H...Cl halide involving hydrogen bonding interactions in between the
      Hoogsteen site hydrogen. CONCLUSIONS: The observed crystal structures emphasize
      the role of the halide ions in developing the supramolecular architectures by
      halide involving hydrogen bonding interactions. Also most of the reported cobalt
      cytokinin complexes possess tetrahedral coordination geometry, but some cobalt
      complexes have distorted octahedral coordination geometry, which are discussed
      and compared. Graphical AbstractSupramolecular architectures of some coordination
      metal complexes of N6-benzyl/furfuryl adenine.

PMID- 25392713
TI  - Risk factors for rehospitalization and inpatient care among pediatric psychiatric
      intake response center patients.
AB  - BACKGROUND: The study sought to explore the characteristics, risk factors for
      inpatient recommendation, and risk factors for revisits to a pediatric
      psychiatric intake response center (PIRC). There are three research questions: 1.
      What is the general profile of pediatric patients who present at the PIRC? 2.
      What are the risk factors for patients who repeatedly visit the PIRC? 3. What are
      the risk factors for PIRC patients who are recommended to inpatient care?
      METHODS: The study utilized a retrospective medical chart review of a random
      sample (n = 260). A PIRC profile was created using frequency and prevalence
      calculations, in addition to a survival analysis of patients who return to the
      PIRC in order to determine how long it takes for PIRC patients to return to the
      PIRC. Factors that contribute to increased odds of returning to PIRC and being
      recommended for inpatient treatment were calculated using two logistic regression
      analyses. RESULTS: The average pediatric PIRC patient is about 13 years old,
      Caucasian, with Medicaid and comes from a divorced or single parent household.
      About 43% of patients presented at PIRC for suicidal thoughts, ideation,
      intentions or actions. At least 63% of patients have a history of victimization.
      The average time to return to PIRC is about 90 days. Patients with a history of
      victimization, suicidal behavior, learning problems, problems with peers, and a
      history of violence were at an increased odds of returning to the PIRC. Those
      patients who were previously admitted to inpatient care and had a family history
      of mental health issues were at increased odds of being recommended to inpatient
      treatment. CONCLUSIONS: This sample presents with a multitude of issues that
      contribute to increased odds of revisits to PIRC and inpatient recommendation.
      These issues seem to come from multiple levels of influence. Future research
      should expand to similar treatment facilities and use a prospective design to
      confirm risk factors. Treatment for pediatric psychiatric patients may focus on
      multiple factors that influence patients' mental health.

PMID- 25392714
TI  - Pilot study: feasibility of using the Suicidal Ideation Questionnaire (SIQ)
      during acute suicidal crisis.
AB  - BACKGROUND: Assessing youths in acute suicidal crisis is a common jet pivotal
      task in child and adolescent psychiatry, usually relying primarily on the
      clinicians skills of assessment. The objective of this pilot-study was to
      evaluate feasibility and usefulness of questionnaires during assessment of youths
      in acute suicidal crisis. METHOD: 31 adolescents, presenting for suicide
      assessment, and their caregivers, were asked upon emergency presentation to fill
      in the Suicidal-Ideation-Questionnaire (SIQ) and the Youth Life Status
      Questionnaire (Y-LSQ) before receiving an assessment by a clinician. The SIQ has
      30 items, 8 of which are defined as critical items able to predict suicidality
      with the highest probability. The Y-LSQ (30 items) measures the overall level of
      psychological distress. It has one suicidal item, which was used in this study
      for validation of the SIQ result. Clinical judgment and test results were
      collected and analyzed by an independent researcher. RESULTS: It was feasible to
      ask adolescents in acute suicidal crisis to fill in a questionnaire. Clinical
      assessment of suicidality did not correlate significantly with the overall SIQ
      score (p = 0.089), however there was a significant correlation between the SIQ 8
      critical item result and clinical judgement of suicidality (p = 0.050).
      CONCLUSION: The 8 critical SIQ items can be used to support clinical judgment of
      suicidality in acute crisis.

PMID- 25392715
TI  - Genomic amplification of MYC as double minutes in a patient with APL-like
      leukemia.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid
      leukemia (AML) characterized by a PML-RARA fusion due to a translocation
      t(15;17). Its sensitivity to treatment with all-trans retinoic acid (ATRA), which
      causes differentiation of the abnormal promyelocytes, combined with anthracycline
      based chemotherapy makes it the best curable subtype of acute myeloid leukemia. A
      rapid and accurate diagnosis is needed in the first place to prevent (more)
      bleeding problems. Here we present a patient with a leukemia with an APL-like
      morphology but no detectable PML-RARA fusion, as demonstrated by RT-PCR and
      cytogenetic analysis. RESULTS: Unexpectedly, karyotyping revealed numerous double
      minutes (dmins). Fluorescence in situ hybridization (FISH) with DNA probes
      specific for the MYC-region showed the presence of multiple MYC amplicons. SNP
      array analysis uncovered amplification of the 8q24.13-q24.21 region, including
      the MYC-gene, flanked by deletions in 8q24.13 and 8q24.21-q24.22, and a
      homozygous deletion in 9p21.3, flanked by heterozygous deletions in the same
      chromosome region. CONCLUSIONS: The diagnosis was revised to AML, not otherwise
      specified (AML, NOS) and therefore therapy with ATRA was discontinued.

PMID- 25392716
TI  - Accurate prediction of major histocompatibility complex class II epitopes by
      sparse representation via l 1-minimization.
AB  - BACKGROUND: The major histocompatibility complex (MHC) is responsible for
      presenting antigens (epitopes) on the surface of antigen-presenting cells (APCs).
      When pathogen-derived epitopes are presented by MHC class II on an APC surface, T
      cells may be able to trigger an specific immune response. Prediction of MHC-II
      epitopes is particularly challenging because the open binding cleft of the MHC-II
      molecule allows epitopes to bind beyond the peptide binding groove; therefore,
      the molecule is capable of accommodating peptides of variable length. Among the
      methods proposed to predict MHC-II epitopes, artificial neural networks (ANNs)
      and support vector machines (SVMs) are the most effective methods. We propose a
      novel classification algorithm to predict MHC-II called sparse representation via
      l 1-minimization. RESULTS: We obtained a collection of experimentally confirmed
      MHC-II epitopes from the Immune Epitope Database and Analysis Resource (IEDB) and
      applied our l 1-minimization algorithm. To benchmark the performance of our
      proposed algorithm, we compared our predictions against a SVM classifier. We
      measured sensitivity, specificity abd accuracy; then we used Receiver Operating
      Characteristic (ROC) analysis to evaluate the performance of our method. The
      prediction performance of MHC-II epitopes of the l 1-minimization algorithm was
      generally comparable and, in some cases, superior to the standard SVM
      classification method and overcame the lack of robustness of other methods with
      respect to outliers. While our method consistently favoured DPPS encoding with
      the alleles tested, SVM showed a slightly better accuracy when "11-factor"
      encoding was used. CONCLUSIONS: l 1-minimization has similar accuracy than SVM,
      and has additional advantages, such as overcoming the lack of robustness with
      respect to outliers. With l 1-minimization no model selection dependency is
      involved.

PMID- 25392719
TI  - Bone tuberculosis simulating an exostosis.

PMID- 25392717
TI  - Staphylococcus aureus gene expression in a rat model of infective endocarditis.
AB  - BACKGROUND: Diabetes mellitus is a frequent underlying comorbidity in patients
      with Staphylococcus aureus endocarditis, and it represents a risk factor for
      complications and a negative outcome. The pathogenesis of staphylococcal
      endocardial infections in diabetic hosts has been poorly characterized, and
      little is known about S. aureus gene expression in endocardial vegetations.
      METHODS: We utilized a rat model of experimental S. aureus endocarditis to
      compare the pathogenesis of staphylococcal infection in diabetic and nondiabetic
      hosts and to study the global S. aureus transcriptome in endocardial vegetations
      in vivo. RESULTS: Diabetic rats had higher levels of bacteremia and larger
      endocardial vegetations than nondiabetic control animals. Microarray analyses
      revealed that 61 S. aureus genes were upregulated in diabetic rats, and the
      majority of these bacterial genes were involved in amino acid and carbohydrate
      metabolism. When bacterial gene expression in vivo (diabetic or nondiabetic
      endocardial vegetations) was compared to in vitro growth conditions, higher in
      vivo expression of genes encoding toxins and proteases was observed.
      Additionally, genes involved in the production of adhesins, capsular
      polysaccharide, and siderophores, as well as in amino acid and carbohydrate
      transport and metabolism, were upregulated in endocardial vegetations. To test
      the contribution of selected upregulated genes to the pathogenesis of
      staphylococcal endocarditis, isogenic deletion mutants were utilized. A mutant
      defective in production of the siderophore staphyloferrin B was attenuated in the
      endocarditis model, whereas the virulence of a surface adhesin (DeltasdrCDE)
      mutant was similar to that of the parental S. aureus strain. CONCLUSIONS: Our
      results emphasize the relevance of diabetes mellitus as a risk factor for
      infectious endocarditis and provide a basis for understanding gene expression
      during staphylococcal infections in vivo.

PMID- 25392718
TI  - VOXEL-LEVEL MAPPING OF TRACER KINETICS IN PET STUDIES: A STATISTICAL APPROACH
      EMPHASIZING TISSUE LIFE TABLES.
AB  - Most radiotracers used in dynamic positron emission tomography (PET) scanning act
      in a linear time-invariant fashion so that the measured time-course data are a
      convolution between the time course of the tracer in the arterial supply and the
      local tissue impulse response, known as the tissue residue function. In
      statistical terms the residue is a life table for the transit time of injected
      radiotracer atoms. The residue provides a description of the tracer kinetic
      information measurable by a dynamic PET scan. Decomposition of the residue
      function allows separation of rapid vascular kinetics from slower blood-tissue
      exchanges and tissue retention. For voxel-level analysis, we propose that
      residues be modeled by mixtures of nonparametrically derived basis residues
      obtained by segmentation of the full data volume. Spatial and temporal aspects of
      diagnostics associated with voxel-level model fitting are emphasized.
      Illustrative examples, some involving cancer imaging studies, are presented. Data
      from cerebral PET scanning with 18F fluoro-deoxyglucose (FDG) and 15O water (H2O)
      in normal subjects is used to evaluate the approach. Cross-validation is used to
      make regional comparisons between residues estimated using adaptive mixture
      models with more conventional compartmental modeling techniques. Simulations
      studies are used to theoretically examine mean square error performance and to
      explore the benefit of voxel-level analysis when the primary interest is a
      statistical summary of regional kinetics. The work highlights the contribution
      that multivariate analysis tools and life-table concepts can make in the recovery
      of local metabolic information from dynamic PET studies, particularly ones in
      which the assumptions of compartmental-like models, with residues that are sums
      of exponentials, might not be certain.

PMID- 25392720
TI  - Suspected azathioprine induced liver cirrhosis: an unusual side effect.
AB  - In recent years, the hepatotoxic potential of thiopurines, in particular 6
      thioguanine (6-TG) has been discussed in literature. However, cirrhosis was
      exceptionally reported. We report the case of a 56-year-old woman with ileocaecal
      Crohn's disease treated with azathioprine. After taking azathioprine (2 mg/kg
      daily) for four years, she underwent surgical treatment for acute intestinal
      obstruction. In peroperative, we noticed a cirrhotic liver. A surgical biopsy was
      performed and the diagnosis of cirrhosis was confirmed. Autoimmune and viral
      liver diseases were ruled out by laboratory parameters. Therefore, Azathioprine
      is believed to be the causative actor for inducing liver cirrhosis. Thus,
      treating inflammatory bowel disease effectively while trying to limit iatrogenic
      disease is a continuous struggle. 

PMID- 25392721
TI  - [Capillary hemangioma of the upper eyelid].

PMID- 25392722
TI  - Liver contusion in man reveals a Tako-tsubo cardiomyopathy without chest pain:
      reality or illusion?
AB  - Tako-tsubo syndrome is very rare in male patients, often overlooked by
      practitioners in its atypical form painless, and who did not always a good
      prognostic, often revealed in a context of acute stress at any time in the
      hospital or outside, its pathophysiology remains to discuss, the diagnosis is
      greatly facilitated by imaging including echocardiography with apical ballooning.
      We relate this clinical case of a patient admitted to the ICU for a liver
      contusion with a diagnosis incidentally this syndrome. 

PMID- 25392723
TI  - Pedro Pons' sign.

PMID- 25392724
TI  - [Feature of bilateral blindness with normal fundus revealing an unruptured
      aneurysm of the anterior communicating cerebral artery].

PMID- 25392725
TI  - Antimicrobial susceptibility patterns of enterobacteriaceae isolated from HIV
      infected patients in Kinshasa.
AB  - INTRODUCTION: People infected by Human Immunodeficiency Virus (HIV) are
      susceptible to develop severe bacterial infections. We set out to determine the
      frequency and the sensitivity to antibiotics of enterobaceriaceae isolated from
      urine and feces of HIV-infected persons. METHODS: Urine and feces samples were
      collected from HIV-infected patients of the Centre de Traitement Ambulatoire de
      Kabinda (CTA/Kabinda, Kinshasa) and analyzed at the Reference National Laboratory
      for HIV/AIDS and Sexually Transmitted Infections. The isolated enterobacteriaceae
      strains were identified by conventional microbiological methods. Antibiotic
      sensitivity pattern was carried out by disc diffusion method. RESULTS: THE
      FOLLOWING BACTERIA PATHOGENS WERE ISOLATED: Escherichia coli, Klebsiella,
      Enterobacter, Proteus, and Providencia. Most species were sensitive to cefotaxim,
      ceftriaxon, and gentamicin and resistant to chloramphenicol, cotrimoxazole,
      tetracycline, and norfloxacin. CONCLUSION: The results of the present study show
      that the most frequently bacteria isolated were Esherichia coli and cefotaxim,
      ceftriaxon, and gentamicin were the most active antibiotics.

PMID- 25392726
TI  - [Solitary bone plasmacytoma: experience of the National Institute of Oncology,
      Rabat (INO)].

PMID- 25392727
TI  - Lessons from an elective in Sierra Leone.

PMID- 25392728
TI  - Socio-demographic and clinical profile of immuno-histochemically confirmed breast
      cancer in a resource limited country.
AB  - INTRODUCTION: Breast cancer is the most common cancer in females. It is the most
      common cause of cancer-related death among women with fatality rates highest in
      low-income countries. The aim of this study is to determine the socio-demographic
      and clinical profile of patients with immunohistochemically confirmed breast
      cancer in a Nigerian tertiary health institution. METHODS: Patients with
      immunohistochemically confirmed breast cancer were reviewed. The information
      retrieved was entered into a proforma designed for the purpose of the study. Data
      was analysed using SPSS version 18.0. RESULTS: The peak incidence of age at
      presentation was in the 5th decade. More than 50% of the patients were
      premenopausal and perimenopausal at presentation. Only 11% of the patients
      presented with breast lumps less than 2 cm in size. Women in the age group 50-59
      years are more likely to present with larger breast lumps than women in other
      groups. More than 50% had clinically palpable lymph node at presentation.
      Mastectomy (simple mastectomy and modified radical mastectomy) and adjuvant
      chemotherapy were the main form of treatment. Most of the cases were estrogen
      receptor negative with majority of them having basal-like subtype. CONCLUSION:
      Most of the patients in this study were not only young but presented with locally
      advanced disease. Population screening, adequate health education, improved
      accessibility and availability of heath care will go a long way to improve the
      outcome of these patients.

PMID- 25392729
TI  - The Autism Simplex Collection: an international, expertly phenotyped autism
      sample for genetic and phenotypic analyses.
AB  - BACKGROUND: There is an urgent need for expanding and enhancing autism spectrum
      disorder (ASD) samples, in order to better understand causes of ASD. METHODS: In
      a unique public-private partnership, 13 sites with extensive experience in both
      the assessment and diagnosis of ASD embarked on an ambitious, 2-year program to
      collect samples for genetic and phenotypic research and begin analyses on these
      samples. The program was called The Autism Simplex Collection (TASC). TASC sample
      collection began in 2008 and was completed in 2010, and included nine sites from
      North America and four sites from Western Europe, as well as a centralized Data
      Coordinating Center. RESULTS: Over 1,700 trios are part of this collection, with
      DNA from transformed cells now available through the National Institute of Mental
      Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic
      Observation Schedule-Generic (ADOS-G) measures are available for all probands, as
      are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the
      Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and
      physical measures (height, weight, and head circumference). At almost every site,
      additional phenotypic measures were collected, including the Broad Autism
      Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as
      well as the non-word repetition scale, Communication Checklist (Children's or
      Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios,
      the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP
      genotyping and called copy number variation (CNV) in the samples, with data being
      made available through the National Institutes of Health (NIH). Whole exome
      sequencing (WES) has been carried out in over 500 probands, together with
      ancestry matched controls, and this data is also available through the NIH.
      Additional WES is being carried out by the Autism Sequencing Consortium (ASC),
      where the focus is on sequencing complete trios. ASC sequencing for the first
      1,000 samples (all from whole-blood DNA) is complete and data will be released in
      2014. Data is being made available through NIH databases (database of Genotypes
      and Phenotypes (dbGaP) and National Database for Autism Research (NDAR)) with DNA
      released in Dist 11.0. Primary funding for the collection, genotyping, sequencing
      and distribution of TASC samples was provided by Autism Speaks and the NIH,
      including the National Institute of Mental Health (NIMH) and the National Human
      Genetics Research Institute (NHGRI). CONCLUSIONS: TASC represents an important
      sample set that leverages expert sites. Similar approaches, leveraging expert
      sites and ongoing studies, represent an important path towards further enhancing
      available ASD samples.

PMID- 25392730
TI  - Ubiquitin-proteasome dependent degradation of GABAAalpha1 in autism spectrum
      disorder.
AB  - BACKGROUND: Although the neurobiological basis of autism spectrum disorder (ASD)
      is not fully understood, recent studies have indicated the potential role of
      GABAA receptors in the pathophysiology of ASD. GABAA receptors play a crucial
      role in various neurodevelopmental processes and adult neuroplasticity. However,
      the mechanism(s) of regulation of GABAA receptors in ASD remains poorly
      understood. METHODS: Postmortem middle frontal gyrus tissues (13 ASD and 13
      control subjects) were used. In vitro studies were performed in primary cortical
      neurons at days in vitro (DIV) 14. The protein levels were examined by western
      blotting. Immunofluorescence studies were employed for cellular localization. The
      gene expression was determined by RT-PCR array and qRT-PCR. RESULTS: A
      significant decrease in GABAAalpha1 protein, but not mRNA levels was found in the
      middle frontal gyrus of ASD subjects indicating a post-translational regulation
      of GABAA receptors in ASD. At the cellular level, treatment with proteasomal
      inhibitor, MG132, or lactacystin significantly increased GABAAalpha1 protein
      levels and Lys48-linked polyubiquitination of GABAAalpha1, but reduced proteasome
      activity in mouse primary cortical neurons (DIV 14 from E16 embryos). Moreover,
      treatment with betulinic acid, a proteasome activator significantly decreased
      GABAAalpha1 protein levels in cortical neurons indicating the role of
      polyubiquitination of GABAAalpha1 proteins with their subsequent proteasomal
      degradation in cortical neurons. Ubiquitination specific RT-PCR array followed by
      western blot analysis revealed a significant increase in SYVN1, an endoplasmic
      reticulum (ER)-associated degradation (ERAD) E3 ubiquitin ligase in the middle
      frontal gyrus of ASD subjects. In addition, the inhibition of proteasomal
      activity by MG132 increased the expression of GABAAalpha1 in the ER. The siRNA
      knockdown of SYVN1 significantly increased GABAAalpha1 protein levels in cortical
      neurons. Moreover, reduced association between SYVN1 and GABAAalpha1 was found in
      the middle frontal gyrus of ASD subjects. CONCLUSIONS: SYVN1 plays a critical
      role as an E3 ligase in the ubiquitin proteasome system (UPS)-mediated
      GABAAalpha1 degradation. Thus, inhibition of the ubiquitin-proteasome-mediated
      GABAAalpha1 degradation may be an important mechanism for preventing GABAAalpha1
      turnover to maintain GABAAalpha1 levels and GABA signaling in ASD.

PMID- 25392731
TI  - Gimme that old time religion: the influence of the healthcare belief system of
      chiropractic's early leaders on the development of x-ray imaging in the
      profession.
AB  - BACKGROUND: Chiropractic technique systems have been historically documented to
      advocate overutilization of radiography. Various rationales for this have been
      explored in the literature. However, little consideration has been given to the
      possibility that the healthcare belief system of prominent early chiropractors
      may have influenced the use of the diagnostic modality through the years. The
      original rationale was the visualisation of chiropractic subluxations, defined as
      bones slightly out of place, pressing on nerves, and ultimately causing disease.
      This paradigm of radiography has survived in parts of the chiropractic
      profession, despite lacking evidence of clinical validity. The purpose of this
      paper is to compare the characteristics of the chiropractic technique systems
      that have utilised radiography for subluxation detection with the characteristics
      of religion, and to discover potential historical links that may have facilitated
      the development of those characteristics. DISCUSSION: Twenty-three currently or
      previously existing technique systems requiring radiography for subluxation
      analysis were found using a search of the internet, books and consultation with
      experts. Evidence of religiosity from the early founders' writings was compared
      with textbooks, published papers, and websites of subsequently developed systems.
      Six criteria denoting religious thinking were developed using definitions from
      various sources. They are: supernatural concepts, claims of supremacy, rules and
      rituals, sacred artefacts, sacred stories, and special language. All of these
      were found to a greater or lesser degree in the publicly available documents of
      all the subluxation-based chiropractic x-ray systems. SUMMARY: The founders and
      early pioneers of chiropractic did not benefit from the current understanding of
      science and research, and therefore substituted deductive and inductive reasoning
      to arrive at conclusions about health and disease in the human body. Some of this
      thinking and rationalisation demonstrably followed a religion-like pattern,
      including BJ Palmer's use of radiography. Although access to scientific methods
      and research education became much advanced and more accessible during the past
      few decades, the publicly available documents of technique systems that used
      radiography for chiropractic subluxation detection examined in this paper
      employed a historically derived paradigm for radiography that displayed
      characteristics in common with religion.

PMID- 25392732
TI  - Herd diagnosis of low pathogen diarrhoea in growing pigs - a pilot study.
AB  - BACKGROUND: The major indication for antibiotic use in Danish pigs is treatment
      of intestinal diseases post weaning. Clinical decisions on antibiotic batch
      medication are often based on inspection of diarrhoeic pools on the pen floor. In
      some of these treated diarrhoea outbreaks, intestinal pathogens can only be
      demonstrated in a small number of pigs within the treated group (low pathogen
      diarrhoea). Termination of antibiotic batch medication in herds suffering from
      such diarrhoea could potentially reduce the consumption of antibiotics in the pig
      industry. The objective of the present pilot study was to suggest criteria for
      herd diagnosis of low pathogen diarrhoea in growing pigs. Data previously
      collected from 20 Danish herds were used to create a case series of clinical
      diarrhoea outbreaks normally subjected to antibiotic treatment. In the present
      study, these diarrhoea outbreaks were classified as low pathogen (<15% of the
      pigs having bacterial intestinal disease) (n =5 outbreaks) or high pathogen
      (>=15% of the pigs having bacterial intestinal disease) (n =15 outbreaks). Based
      on the case series, different diagnostic procedures were explored, and criteria
      for herd diagnosis of low pathogen diarrhoea were suggested. The effect of
      sampling variation was explored by simulation. RESULTS: The diagnostic procedure
      with the highest combined herd-level sensitivity and specificity was qPCR testing
      of a pooled sample containing 20 randomly selected faecal samples. The criteria
      for a positive test result (high pathogen diarrhoea outbreak) were an average of
      1.5 diarrhoeic faecal pools on the floor of each pen in the room under
      investigation and a pathogenic bacterial load >=35,000 per gram in the faecal
      pool tested by qPCR. The bacterial load was the sum of Lawsonia intracellularis,
      Brachyspira pilosicoli and Escherichia coli F4 and F18 bacteria per gram faeces.
      The herd-diagnostic performance was (herd-level) diagnostic sensitivity =0.99,
      diagnostic specificity =0.80, positive predictive value =0.94 and negative
      predictive value =0.96. CONCLUSIONS: The pilot study suggests criteria for herd
      diagnosis of low pathogen diarrhoea in growing pigs. The suggested criteria
      should now be evaluated, and the effect of terminating antibiotic batch
      medication in herds identified as suffering from low pathogen diarrhoea should be
      explored.

PMID- 25392733
TI  - Molecular analysis of bacterial diversity in mudflats along the salinity gradient
      of an acidified tropical Bornean estuary (South East Asia).
AB  - BACKGROUND: The Brunei River and Bay estuarine system (BES) in the northwest of
      Borneo is acidic and highly turbid. The system supports extensive intertidal
      mudflats and presents a potentially steep salinity and pH gradient along its
      length (45 km). Temporal variation in physical parameters is observed diurnally
      due to seawater flux during tidal forcing, and stochastically due to elevated
      freshwater inflow after rains, resulting in a salinity range between 0 and 34
      psu. High velocity freshwater run-off from acid sulphate formations during
      monsoon seasons results in highly variable and acidic conditions (pH 4) at the
      upper reaches of the BES, whereas the pH is relatively stable (pH 8) at the
      seaward extremes, due to mixing with seawater from the South China Sea. At their
      surfaces, the BES mudflats present microbial ecosystems driven by oxygenic
      phototrophs. To study the effect of various physical parameters on the bacterial
      diversity of the BES mudflats, surface samples were collected from six sites
      stretching over 40 km for molecular and phylogentic analysis. RESULTS: The
      bacterial diversity at these sites was compared by community fingerprinting
      analysis using 16S rRNA gene based denaturing gradient gel electrophoresis and by
      16S rRNA gene sequencing and phylogenetic analyses. Results revealed functionally
      conserved, diatom-driven microbial mudflat communities composed of mainly novel,
      uncultured species. Species composition was evaluated as 50-70% unique for each
      site along the BES. Clustering of the sequences commonly occurred and revealed
      that proteobacterial diversity was related to the salinity gradient. When
      considering all phyla, the diversity varied consistently with physical parameters
      (including anthropogenic) that are expected to influence microbial composition.
      CONCLUSION: The BES mudflats were found to comprise the typical functional groups
      of microorganisms associated with photosynthetic carbon flux, sulfur cycling
      (Gamma- and Deltaproteobacteria), and decomposition (Bacteroidetes). From a
      structural perspective, however, the mudflats constituted discretely distributed
      communities along the physical gradient of the BES, composed of largely novel
      species of Bacteria. This study provides first insights into patterns of
      bacterial community structure in tropical South East Asian coastal ecosystems
      that are potentially threatened by increasing variability in pH and salinity, in
      line with predicted future environmental change.

PMID- 25392734
TI  - Free breathing myocardial perfusion data sets for performance analysis of motion
      compensation algorithms.
AB  - BACKGROUND: Perfusion quantification by using first-pass gadolinium-enhanced
      myocardial perfusion magnetic resonance imaging (MRI) has proved to be a reliable
      tool for the diagnosis of coronary artery disease that leads to reduced blood
      flow to the myocardium. The image series resulting from such acquisition usually
      exhibits a breathing motion that needs to be compensated for if a further
      automatic analysis of the perfusion is to be executed. Various algorithms have
      been presented to facilitate such a motion compensation, but the lack of publicly
      available data sets hinders a proper, reproducible comparison of these
      algorithms. MATERIAL: Free breathing perfusion MRI series of ten patients
      considered clinically to have a stress perfusion defect were acquired; for each
      patient a rest and a stress study was executed. Manual segmentations of the left
      ventricle myocardium and the right-left ventricle insertion point are provided
      for all images in order to make a unified validation of the motion compensation
      algorithms and the perfusion analysis possible. In addition, all the scripts and
      the software required to run the experiments are provided alongside the data, and
      to enable interested parties to directly run the experiments themselves, the test
      bed is also provided as a virtual hard disk. FINDINGS: To illustrate the utility
      of the data set two motion compensation algorithms with publicly available
      implementations were applied to the data and earlier reported results about the
      performance of these algorithms could be confirmed. CONCLUSION: The data
      repository alongside the evaluation test bed provides the option to reliably
      compare motion compensation algorithms for myocardial perfusion MRI. In addition,
      we encourage that researchers add their own annotations to the data set, either
      to provide inter-observer comparisons of segmentations, or to make other
      applications possible, for example, the validation of segmentation algorithms.

PMID- 25392735
TI  - A comprehensive resource of genomic, epigenomic and transcriptomic sequencing
      data for the black truffle Tuber melanosporum.
AB  - BACKGROUND: Tuber melanosporum, also known in the gastronomic community as
      "truffle", features one of the largest fungal genomes (125 Mb) with an
      exceptionally high transposable element (TE) and repetitive DNA content (>58%).
      The main purpose of DNA methylation in fungi is TE silencing. As obligate
      outcrossing organisms, truffles are bound to a sexual mode of propagation, which
      together with TEs is thought to represent a major force driving the evolution of
      DNA methylation. Thus, it was of interest to examine if and how T. melanosporum
      exploits DNA methylation to maintain genome integrity. FINDINGS: We performed
      whole-genome DNA bisulfite sequencing and mRNA sequencing on different
      developmental stages of T. melanosporum; namely, fruitbody ("truffle"), free
      living mycelium and ectomycorrhiza. The data revealed a high rate of cytosine
      methylation (>44%), selectively targeting TEs rather than genes with a strong
      preference for CpG sites. Whole genome DNA sequencing uncovered multiple TE
      enriched, copy number variant regions bearing a significant fraction of
      hypomethylated and expressed TEs, almost exclusively in free-living mycelium
      propagated in vitro. Treatment of mycelia with 5-azacytidine partially reduced
      DNA methylation and increased TE transcription. Our transcriptome assembly also
      resulted in the identification of a set of novel transcripts from 614 genes.
      CONCLUSIONS: The datasets presented here provide valuable and comprehensive
      (epi)genomic information that can be of interest for evolutionary genomics
      studies of multicellular (filamentous) fungi, in particular Ascomycetes belonging
      to the subphylum, Pezizomycotina. Evidence derived from comparative methylome and
      transcriptome analyses indicates that a non-exhaustive and partly reversible
      methylation process operates in truffles.

PMID- 25392736
TI  - Evaluation of early implementations of antibiotic stewardship program initiatives
      in nine Dutch hospitals.
AB  - BACKGROUND: Antibiotic resistance is a global threat to patient safety and care.
      In response, hospitals start antibiotic stewardship programs to optimise
      antibiotic use. Expert-based guidelines recommend strategies to implement such
      programs, but local implementations may differ per hospital. Earlier published
      assessments determine maturity of antibiotic stewardship programs based on expert
      based structure indicators, but they disregard that there may be valid deviations
      from these expert-based programs. AIM: To analyse the progress and barriers of
      local implementations of antibiotic stewardship programs with stakeholders in
      nine Dutch hospitals and to develop a toolkit that guides implementing local
      antibiotic stewardship programs. METHODS: An online questionnaire based on
      published guidelines and recommendations, conducted with seven clinical
      microbiologists, seven infectious disease physicians and five clinical
      pharmacists at nine Dutch hospitals. RESULTS: Results show local differences in
      antibiotic stewardship programs and the uptake of interventions in hospitals.
      Antibiotic guidelines and antibiotic teams are the most extensively implemented
      interventions. Education, decision support and audit-feedback are deemed
      important interventions and they are either piloted in implementations at
      academic hospitals or in preparation for application in non-academic hospitals.
      Other interventions that are recommended in guidelines - benchmarking,
      restriction and antibiotic formulary - appear to have a lower priority. Automatic
      stop-order, pre-authorization, automatic substitution, antibiotic cycling are not
      deemed to be worthwhile according to respondents. CONCLUSION: There are extensive
      local differences in the implementation of antibiotic stewardship interventions.
      These differences suggest a need to further explore the rationale behind the
      choice of interventions in antibiotic stewardship programs. Rather than reporting
      this rationale, this study reports where rationale can play a key role in the
      implementation of antibiotic stewardship programs. A one-size-fits-all solution
      is unfeasible as there may be barriers or valid reasons for local experts to
      deviate from expert-based guidelines. Local experts can be supported with a
      toolkit containing advice based on possible barriers and considerations. These
      parameters can be used to customise an implementation of antibiotic stewardship
      programs to local needs (while retaining its expert-based foundation).

PMID- 25392737
TI  - A 'giant' paraganglioma in the testis.
AB  - Until now, less than ten cases of extra-adrenal chromaffin cell tumors have been
      reported to be localized to the spermatic cord area. All published studies report
      benign tumors with a diameter <2-3 cm and no invasion of the testis. In this
      article, we present one case of a giant malignant paraganglioma in the testis of
      a patient who had initially been operated for a giant mass in the scrotum. The
      mass developed in approximately 4 months. This is the first study reporting the
      following findings: i) paraganglioma was found exclusively in the testis,
      invading the testicle and not the spermatic cord, ii) it was malignant with lung
      metastasis, and iii) its size was 17.5 cm*10 cm*9.5 cm. We present the first -
      giant - malignant paraganglioma. Moreover, it is the first case report of a
      paraganglioma in the testis. LEARNING POINTS: This is the first study reporting
      the following findings:Paraganglioma found exclusively in the testis, invading
      the testicle and not the spermatic cord.It is malignant with lung metastasis.It
      is of the size 17.5 cm*10 cm*9.5 cm.

PMID- 25392738
TI  - Cilostazol increases patency and reduces adverse outcomes in percutaneous
      femoropopliteal revascularisation: a meta-analysis of randomised controlled
      trials.
AB  - BACKGROUND: Cilostazol is an oral antiplatelet agent currently indicated for
      treatment of intermittent claudication. There is evidence that cilostazol may
      reduce femoropopliteal restenosis after percutaneous endovascular intervention.
      METHODS: We searched PubMed, Scopus and Cochrane databases from 1966 through
      September 2013 for randomised controlled trials (RCTs) evaluating the addition of
      cilostazol to standard care in patients receiving femoropopliteal endovascular
      treatment. Restenosis, target lesion revascularisation and combined adverse
      outcomes (death, revascularisation and amputation) within 1-2 years postprocedure
      were evaluated. RESULTS: Of 205 articles, three RCTs were included in the
      analysis. The pooled data provided a total of 396 patients, 195 of whom received
      cilostazol. When compared to standard medical therapy alone, cilostazol
      significantly reduced the risk of restenosis (risk difference -0.20; 95% CI -0.29
      to -0.11; p<0.0001; number needed to treat 5), target lesion revascularisation
      (risk difference -0.17; 95% CI -0.25 to -0.09; p<0.0001; number needed to treat
      6). Death and amputation were not different in between groups. CONCLUSIONS AND
      LIMITATION: Cilostazol significantly increases femoropopliteal patency and
      decreases adverse outcomes in percutaneous endovascular intervention. However,
      further RCTs are needed because of limited sample size; this meta-analysis
      represents the best current evidence.

PMID- 25392739
TI  - Subcutaneous administration of D-luciferin is an effective alternative to
      intraperitoneal injection in bioluminescence imaging of xenograft tumors in nude
      mice.
AB  - Currently, intraperitoneal (IP) injection of D-luciferin is the preferred method
      of providing substrate for bioluminescent imaging (BLI); however it has a failure
      rate of 3-10% due to accidental intestinal injection. The present study evaluates
      the quality of BLI after subcutaneous (SC) injection of D-luciferin and
      demonstrates the effectiveness of SC injection in anatomically disparate tumor
      models. Mice bearing luciferase-expressing tumors underwent BLI after SC or IP
      injection of D-luciferin. The average time to maximal luminescence was 6 min
      (range 5-9 min) after SC injection and 8 min (range 5-8 min) after IP injection.
      Within 7 minutes of injection, SC and IP routes yielded similar luminescence in
      subcutaneous, intracranial, tongue, and lung xenograft tumor models. In a model
      of combined subcutaneous and intracranial xenografts, SC injection resulted in
      proportional luminescence at all sites, confirming that preferential delivery of
      substrate does not occur. While tumors were occasionally not visualized with IP
      injection, all tumors were visualized reliably with SC injection. Thus, SC
      injection of D-luciferin is a convenient and effective alternative to IP
      injection for BLI in nude mice. It may be a preferable approach, particularly for
      tumors with weaker signals and/or when greater precision is required.

PMID- 25392740
TI  - Endoplasmic Reticulum Stress and Microvascular Endothelial Dysfunction in
      Diabetes.

PMID- 25392741
TI  - Analysis of Drug Interactions with Lipoproteins by High-Performance Affinity
      Chromatography.
AB  - Lipoproteins such as high-density lipoprotein (HDL) and low-density lipoprotein
      (LDL) are known to interact with drugs and other solutes in blood. These
      interactions have been examined in the past by methods such as equilibrium
      dialysis and capillary electrophoresis. This chapter describes an alternative
      approach that has recently been developed for examining these interactions by
      using high-performance affinity chromatography. In this method, lipoproteins are
      covalently immobilized to a solid support and used within a column as a
      stationary phase for binding studies. This approach allows the same lipoprotein
      preparation to be used for a large number of binding studies, leading to precise
      estimates of binding parameters. This chapter will discuss how this technique can
      be applied to the identification of interaction models and be used to
      differentiate between systems that have interactions based on partitioning,
      adsorption or mixed-mode interactions. It is also shown how this approach can
      then be used for the measurement of binding parameters for HDL and LDL with
      drugs. Examples of these studies are provided, with particular attention being
      given to the use of frontal analysis to examine the interactions of R- and S
      propranolol with HDL and LDL. The advantages and possible limitations of this
      method are described. The extension of this approach to other types of drug
      lipoprotein interactions is also considered.

PMID- 25392742
TI  - Adoption of a High-Impact Innovation in a Homogeneous Population.
AB  - Adoption of innovations, whether new ideas, technologies, or products, is
      crucially important to knowledge societies. The landmark studies of adoption
      dealt with innovations having great societal impact (such as antibiotics or
      hybrid crops) but where determining the utility of the innovation was
      straightforward (such as fewer side effects or greater yield). Recent large-scale
      studies of adoption were conducted within heterogeneous populations and focused
      on products with little societal impact. Here, we focus on a case with great
      practical significance: adoption by small groups of highly trained individuals of
      innovations with large societal impact but for which it is impractical to
      determine the true utility of the innovation. Specifically, we study
      experimentally the adoption by critical care physicians of a diagnostic assay
      that complements current protocols for the diagnosis of life-threatening
      bacterial infections and for which a physician cannot estimate the true accuracy
      of the assay based on personal experience. We show through computational modeling
      of the experiment that infection-spreading models-which have been formalized as
      generalized contagion processes-are not consistent with the experimental data,
      while a model inspired by opinion models is able to reproduce the empirical data.
      Our modeling approach enables us to investigate the efficacy of different
      intervention schemes on the rate and robustness of innovation adoption in the
      real world. While our study is focused on critical care physicians, our findings
      have implications for other settings in education, research, and business, where
      small groups of highly qualified peers make decisions about the adoption of
      innovations whose utility is difficult if not impossible to gauge.

PMID- 25392743
TI  - Rationale for Using Social Media to Collect Patient-Reported Outcomes in Patients
      with Celiac Disease.
AB  - Patients with celiac disease (CD) are increasingly interconnected through social
      media, exchanging patient experiences and health-tracking information between
      individuals through various web-based platforms. Social media represents
      potentially unique communication interface between gastroenterologists and active
      social media users - especially young adults and adolescents with celiac disease
      regarding adherence to the strict gluten-free diet, gastrointestinal symptoms,
      and meaningful discussion about disease management. Yet, various social media
      platforms may be underutilized for research purposes to collect patient-reported
      outcomes data. In this commentary, we summarize the scientific rationale and
      potential for future growth of social media in patient-reported outcomes
      research, focusing on college freshmen with celiac disease as a case study and
      provide overview of the methodological approach. Finally, we discuss how social
      media may impact patient care in the future through increasing mobile technology
      use.

PMID- 25392744
TI  - Molecular Strategies of Deoxynucleotide Triphosphate Supply Inhibition Used in
      the Treatment of Gynecologic Malignancies.
AB  - Chemotherapies targeting deoxynucleotide triphosphate synthesis are of high
      medical interest in the treatment of gynecologic malignancies. In this article,
      we focus on targeted inhibitors of ribonucleotide reductase, an enzyme in charge
      of ribonucleotide reduction to their corresponding deoxyribonucleotide to be used
      as the building blocks of DNA. We also discuss human clinical trials have
      utilized ribonucleotide reductase subunit-specific inhibitors, particularly
      trials for women with cervical cancer.

PMID- 25392745
TI  - DL-PRO: A Novel Deep Learning Method for Protein Model Quality Assessment.
AB  - Computational protein structure prediction is very important for many
      applications in bioinformatics. In the process of predicting protein structures,
      it is essential to accurately assess the quality of generated models. Although
      many single-model quality assessment (QA) methods have been developed, their
      accuracy is not high enough for most real applications. In this paper, a new
      approach based on C-alpha atoms distance matrix and machine learning methods is
      proposed for single-model QA and the identification of native-like models.
      Different from existing energy/scoring functions and consensus approaches, this
      new approach is purely geometry based. Furthermore, a novel algorithm based on
      deep learning techniques, called DL-Pro, is proposed. For a protein model, DL-Pro
      uses its distance matrix that contains pairwise distances between two residues' C
      alpha atoms in the model, which sometimes is also called contact map, as an
      orientation-independent representation. From training examples of distance
      matrices corresponding to good and bad models, DL-Pro learns a stacked
      autoencoder network as a classifier. In experiments on selected targets from the
      Critical Assessment of Structure Prediction (CASP) competition, DL-Pro obtained
      promising results, outperforming state-of-the-art energy/scoring functions,
      including OPUS-CA, DOPE, DFIRE, and RW.

PMID- 25392746
TI  - Prospective Development of Small Molecule Targets to Oncogenic Ras Proteins.
AB  - Abnormal expression or mutations in Ras proteins has been found in up to 30% of
      cancer cell types, making them excellent protein models to probe structure
      function relationships of cell-signaling processes that mediate cell
      transformtion. Yet, there has been very little development of therapies to help
      tackle Ras-related diseased states. The development of small molecules to target
      Ras proteins to potentially inhibit abnormal Ras-stimulated cell signaling has
      been conceptualized and some progress has been made over the last 16 or so years.
      Here, we briefly review studies characterizing Ras protein-small molecule
      interactions to show the importance and potential that these small molecules may
      have for Ras-related drug discovery. We summarize recent results, highlighting
      small molecules that can be directly targeted to Ras using Structure-Based Drug
      Design (SBDD) and Fragment-Based Lead Discovery (FBLD) methods. The inactivation
      of Ras oncogenic signaling in vitro by small molecules is currently an attractive
      hurdle to try to and leap over in order to attack the oncogenic state. In this
      regard, important features of previously characterized properties of small
      molecule Ras targets, as well as a current understanding of conformational and
      dynamics changes seen for Ras-related mutants, relative to wild type, must be
      taken into account as newer small molecule design strategies towards Ras are
      developed.

PMID- 25392747
TI  - The influence of biofilms in the biology of plasmids.
AB  - The field of plasmid biology has historically focused on bacteria growing in
      liquid culture. Surface attached communities of bacterial biofilms have recently
      been understood to be the normal environment of bacteria in the natural world.
      Thus, studies examining plasmid replication, maintenance, and transfer in
      biofilms are essential for a true understanding of bacterial plasmid biology.
      This chapter reviews the current knowledge of the interplay between bacterial
      biofilms and plasmids, focusing on the role of plasmids in biofilm development
      and the role of biofilms in plasmid maintenance, copy number control, and
      transfer. The studies examined herein highlight the importance of biofilms as an
      important ecological niche in which bacterial plasmids play an essential role.

PMID- 25392749
TI  - Automatic identification of species with neural networks.
AB  - A new automatic identification system using photographic images has been designed
      to recognize fish, plant, and butterfly species from Europe and South America.
      The automatic classification system integrates multiple image processing tools to
      extract the geometry, morphology, and texture of the images. Artificial neural
      networks (ANNs) were used as the pattern recognition method. We tested a data set
      that included 740 species and 11,198 individuals. Our results show that the
      system performed with high accuracy, reaching 91.65% of true positive fish
      identifications, 92.87% of plants and 93.25% of butterflies. Our results
      highlight how the neural networks are complementary to species identification. 

PMID- 25392748
TI  - Testosterone Supplementation Improves Carbohydrate and Lipid Metabolism in Some
      Older Men with Abdominal Obesity.
AB  - BACKGROUND/OBJECTIVES: The effects of testosterone supplementation on
      carbohydrate and lipid metabolism in obese older men are uncertain. We conducted
      a single-arm open-label prospective pilot study to investigate the effects of
      testosterone supplementation on central and peripheral insulin sensitivity in
      older men with upper body obesity and insulin resistance. SUBJECTS/METHODS:
      Twenty men (62-78 years-old) with morning testosterone levels <13.9 nmol/L (400
      ng/dL), waist circumference >= 102 cm, and HOMA-IR >= 4.0 or HgbA1C 5.7-6.4%
      applied transdermal testosterone (10 mg) daily for 20 weeks. Insulin sensitivity
      (Si) was determined by a 2-stage glucose clamp, liver and intramyocellular lipid
      by 1H-MR spectroscopy and body composition by DEXA. RESULTS: Testosterone
      supplementation significantly reduced total fat (-.9 +/- 2.4 kg, p=0.002), trunk
      fat (-1.3 +/- 1.4 kg, p=0.0007) and extremity fat (-0.7 +/- 1.1 kg, p=0.01), and
      increased extremity lean tissue (+1.3 +/- 1.4 kg, p=0.0006). Whole body (WB) Si
      improved by 21% (0.76 +/- 1.57 dL/min per uU/mL, p=0.04) and insulin-stimulated
      glucose uptake (Rd) by 24% (0.91 +/- 1.74 dL/min per uU/mL, p=0.03). Improvements
      in glucose kinetics were limited to men with reductions in trunk and extremity
      fat greater than median declines for the entire group. Reductions in
      intramyocellular lipid were associated with improvements in WB Si (p=0.04) and Rd
      (p=0.03). Change in Rd accounted for 90% of the change in WB Si. Hepatic glucose
      output and liver lipid/H2O were unchanged (p>0.05). Multivariable analyses
      revealed that reductions in extremity fat, trunk fat, and FFA levels during the
      clamp accounted for 45% (p=0.004), 31% (p=0.002) and 8% (p=0.04) of respective
      changes in Rd. Triglycerides decreased by -0.40 +/- 0.67mmol/L (p=0.02), LDL-C by
      0.35 +/- 0.57 mmol/L (p=0.02), and HDL-C by -0.14 +/- 0.19 mmol/L (p=0.004).
      CONCLUSIONS: Testosterone supplementation that resulted in greater reductions in
      regional adiposity was associated with improved insulin sensitivity, lower LDL-C
      and fasting triglycerides, but lower HDL-C. Placebo controlled trials need to
      further examine the potential cardiometabolic risks/benefits of androgen
      supplementation for older men with low testosterone levels, central obesity, and
      insulin resistance.

PMID- 25392750
TI  - Utilization of maternal healthcare among adolescent mothers in urban India:
      evidence from DLHS-3.
AB  - Background. Low use of maternal healthcare services is one of the reasons why
      maternal mortality is still considerably high among adolescents mothers in India.
      To increase the utilization of these services, it is necessary to identify
      factors that affect service utilization. To our knowledge, no national level
      study in India has yet examined the issue in the context urban adolescent
      mothers. The present study is an attempt to fill this gap. Data and Methods.
      Using information from the third wave of District Level Household Survey (2007
      08), we have examined factors associated with the utilization of maternal
      healthcare services among urban Indian married adolescent women (aged 13-19
      years) who have given live/still births during last three years preceding the
      survey. The three outcome variables included in the analyses are 'full antenatal
      care (ANC)', 'safe delivery' and 'postnatal care within 42 days of delivery'. We
      have used Chi-square test to determine the difference in proportion and the
      binary logistic regression to understand the net effect of predictor variables on
      the utilization of maternity care. Results. About 22.9% of mothers have received
      full ANC, 65.1% of mothers have had at least one postnatal check-up within 42
      days of pregnancy. The proportion of mother having a safe delivery, i.e.,
      assisted by skilled personnel, is about 70.5%. Findings indicate that there is
      considerable amount of variation in use of maternity care by educational
      attainment, household wealth, religion, parity and region of residence. Receiving
      full antenatal care is significantly associated with mother's education,
      religion, caste, household wealth, parity, exposure to healthcare messages and
      region of residence. Mother's education, full antenatal care, parity, household
      wealth, religion and region of residence are also statistically significant in
      case of safe delivery. The use of postnatal care is associated with household
      wealth, woman's education, full antenatal care, safe delivery care and region of
      residence. Conclusion. Several socioeconomic and demographic factors affect the
      utilization of maternal healthcare services among urban adolescent women in
      India. Promoting the use of family planning, female education and higher age at
      marriage, targeting vulnerable groups such as poor, illiterate, high parity
      women, involving media and grass root level workers and collaboration between
      community leaders and health care system could be some important policy level
      interventions to address the unmet need of maternity services among urban
      adolescents. 

PMID- 25392751
TI  - Changes in species diversity of arboreal spiders in Mexican coffee
      agroecosystems: untangling the web of local and landscape influences driving
      diversity.
AB  - Agricultural intensification is implicated as a major driver of global
      biodiversity loss. Local management and landscape scale factors both influence
      biodiversity in agricultural systems, but there are relatively few studies to
      date looking at how local and landscape scales influence biodiversity in tropical
      agroecosystems. Understanding what drives the diversity of groups of organisms
      such as spiders is important from a pragmatic point of view because of the
      important biocontrol services they offer to agriculture. Spiders in coffee are
      somewhat enigmatic because of their positive or lack of response to agricultural
      intensification. In this study, we provide the first analysis, to our knowledge,
      of the arboreal spiders in the shade trees of coffee plantations. In the
      Soconusco region of Chiapas, Mexico we sampled across 38 sites on 9 coffee
      plantations. Tree and canopy connectedness were found to positively influence
      overall arboreal spider richness and abundance. We found that different
      functional groups of spiders are responding to different local and landscape
      factors, but overall elevation was most important variable influencing arboreal
      spider diversity. Our study has practical management applications that suggest
      having shade grown coffee offers more suitable habitat for arboreal spiders due
      to a variety of the characteristics of the shade trees. Our results which show
      consistently more diverse arboreal spider communities in lower elevations are
      important in light of looming global climate change. As the range of suitable
      elevations for coffee cultivation shrinks promoting arboreal spider diversity
      will be important in sustaining the viability of coffee. 

PMID- 25392752
TI  - Evidence for coal forest refugia in the seasonally dry Pennsylvanian tropical
      lowlands of the Illinois Basin, USA.
AB  - The Moscovian plant macroflora at Cottage Grove southeastern Illinois, USA, is a
      key example of Pennsylvanian (323-299 Million years ago) dryland vegetation.
      There is currently no palynological data from the same stratigraphic horizons as
      the plant macrofossils, leaves and other vegetative and reproductive structures,
      at this locality. Consequently, reconstructions of the standing vegetation at
      Cottage Grove from these sediments lack the complementary information and a more
      regional perspective that can be provided by sporomorphs (prepollen, pollen,
      megaspores and spores). In order to provide this, we have analysed the
      composition of fossil sporomorph assemblages in two rock samples taken from
      macrofossil-bearing inter-coal shale at Cottage Grove. Our palynological data
      differ considerably in composition and in the dominance-diversity profile from
      the macrofossil vegetation at this locality. Walchian conifers and pteridosperms
      are common elements in the macroflora, but are absent in the sporomorph
      assemblages. Reversely, the sporomorph assemblages at Cottage Grove comprise 17
      spore taxa (~16% and ~63% of the total assemblages) that are known from the
      lycopsid orders Isoetales, Lepidodendrales and Selaginallales, while Cottage
      Grove's macrofloral record fails to capture evidence of a considerable population
      of coal forest lycopsids. We interpret our results as evidence that the
      Pennsylvanian dryland glacial landscape at Cottage Grove included fragmented
      populations of wetland plants living in refugia. 

PMID- 25392753
TI  - Evolving California genotypes of Avena barbata are derived from multiple
      introductions but still maintain substantial population structure.
AB  - Multiple introductions are thought to enhance the chance of successful
      colonization, in part because recombination may generate adaptive variation to a
      new environment. Avena barbata (slender wild oat) is a successful colonist in
      California, historically noted for striking genetic divergence into two
      multilocus genotypes, but is still undergoing adaptive change. We sought to
      understand whether multiple introductions might be contributing to this change.
      We used cpDNA phylogeography of A. barbata within its home range and in its
      invaded range in California to determine the minimum number of separate
      introductions, and the spatial distribution of these introduced lineages. We
      collected from sites throughout the state of California, where it is an invasive
      species. Accessions from a representative portion of A. barbata's full native
      range were obtained from germplasm repositories. We sequenced seven intergenic
      chloroplast DNA loci for A. barbata individuals both in California (novel
      geographic range) and its ancestral range. 204 individuals were assayed for
      chloroplast haplotype within California using single strand conformational
      polymorphism SSCPs. Genome size was determined by flow cytometry. Californian
      accessions are tetraploid as expected, but their genome sizes were smaller than
      the Old World accessions. There were three haplotypes present in California that
      were identical to haplotypes in the native range. Within California, the presence
      of multiple haplotypes at a site was observed primarily in Northern and Central
      populations. Between populations there was still substantial structure with F ST
      ~ 0.33, due to a shallow latitudinal cline caused by a preponderance of xeric
      haplotypes in Southern California. There was a minimum of three seed
      introductions to California. Recombination is thus likely to occur, and
      contribute to adaptation in new range in this highly-selfing, invader. 

PMID- 25392754
TI  - Fish market prices drive overfishing of the 'big ones'.
AB  - The relationship between fish market price and body size has not been explored
      much in fisheries science. Here, the mean market prices and fish body size were
      collected in order to examine the hypothesis that large fish, both among- and
      within-species, are being selectively targeted by fisheries because they may
      yield greater profit. Trophic levels, vulnerability to fishing and global
      landings were also collected because these variables may also be related to the
      market fish price. These relationships were examined using generalized additive
      models (GAM), which showed that, among species, fish market price was positively
      dependent on maximum total length (P = 0.0024) and negatively on landings (P =
      0.0006), whereas it was independent of trophic level (P > 0.05) and vulnerability
      to fishing (P > 0.05). When the fish price vs. size relationship was tested
      within-species, large individuals were consistently attaining higher market
      prices compared to their medium and small-sized counterparts. We conclude that
      the selective removal of the larger fish, which is driven by their market price
      and to a lesser extent by their availability, may contribute to their
      overfishing. 

PMID- 25392755
TI  - Quantitative measurement of odor detection thresholds using an air dilution
      olfactometer, and association with genetic variants in a sample of diverse
      ancestry.
AB  - Genetic association studies require a quantitative and reliable method for odor
      threshold assessment in order to examine the contribution of genetic variants to
      complex olfactory phenotypes. Our main goal was to assess the feasibility of a
      portable Scentroid air dilution olfactometer for use in such studies. Using the
      Scentroid SM110C and the SK5 n-butanol Sensitivity Kit (IDES Canada Inc.), n
      butanol odor thresholds were determined for 182 individuals of diverse ancestry
      (mean age: 20.4 +/- 2.5 years; n = 128 female; n = 54 male). Threshold scores
      from repeat participants were used to calculate a test-retest reliability
      coefficient, which was statistically significant (r = 0.754, p < 0.001, n = 29),
      indicating that the Scentroid provides reliable estimates of odor thresholds. In
      addition, we performed a preliminary genetic analysis evaluating the potential
      association of n-butanol odor thresholds to six single-nucleotide polymorphisms
      (SNPs) putatively involved in general olfactory sensitivity (GOS). The results of
      multiple linear regression analysis revealed no significant association between
      the SNPs tested and threshold scores. However, our sample size was relatively
      small, and our study was only powered to identify genetic markers with strong
      effects on olfactory sensitivity. Overall, we find that the Scentroid provides
      reliable quantitative measures of odor detection threshold and is well suited for
      genetic studies of olfactory sensitivity. 

PMID- 25392756
TI  - Unipro UGENE NGS pipelines and components for variant calling, RNA-seq and ChIP
      seq data analyses.
AB  - The advent of Next Generation Sequencing (NGS) technologies has opened new
      possibilities for researchers. However, the more biology becomes a data-intensive
      field, the more biologists have to learn how to process and analyze NGS data with
      complex computational tools. Even with the availability of common pipeline
      specifications, it is often a time-consuming and cumbersome task for a bench
      scientist to install and configure the pipeline tools. We believe that a unified,
      desktop and biologist-friendly front end to NGS data analysis tools will
      substantially improve productivity in this field. Here we present NGS pipelines
      "Variant Calling with SAMtools", "Tuxedo Pipeline for RNA-seq Data Analysis" and
      "Cistrome Pipeline for ChIP-seq Data Analysis" integrated into the Unipro UGENE
      desktop toolkit. We describe the available UGENE infrastructure that helps
      researchers run these pipelines on different datasets, store and investigate the
      results and re-run the pipelines with the same parameters. These pipeline tools
      are included in the UGENE NGS package. Individual blocks of these pipelines are
      also available for expert users to create their own advanced workflows. 

PMID- 25392757
TI  - Training understanding of reversible sentences: a study comparing language
      impaired children with age-matched and grammar-matched controls.
AB  - Introduction. Many children with specific language impairment (SLI) have problems
      with language comprehension, and little is known about how to remediate these. We
      focused here on errors in interpreting sentences such as "the ball is above the
      cup", where the spatial configuration depends on word order. We asked whether
      comprehension of such short reversible sentences could be improved by
      computerized training, and whether learning by children with SLI resembled that
      of younger, typically-developing children. Methods. We trained 28 children with
      SLI aged 6-11 years, 28 typically-developing children aged from 4 to 7 years who
      were matched to the SLI group for raw scores on a test of receptive grammar, and
      20 typically-developing children who were matched to the SLI group on
      chronological age. A further 20 children with SLI were given pre- and post-test
      assessments, but did not undergo training. Those in the trained groups were given
      training on four days using a computer game adopting an errorless learning
      procedure, during which they had to select pictures to correspond to spoken
      sentences such as "the cup is above the drum" or "the bird is below the hat".
      Half the trained children heard sentences using above/below and the other half
      heard sentences using before/after (with a spatial interpretation). A total of 96
      sentences was presented over four sessions. Half the sentences were unique,
      whereas the remainder consisted of 12 repetitions of each of four sentences that
      became increasingly familiar as training proceeded. Results. Age-matched control
      children performed near ceiling (>= 90% correct) in the first session and were
      excluded from the analysis. Around half the trained SLI children also performed
      this well. Training effects were examined in 15 SLI and 16 grammar-matched
      children who scored less than 90% correct on the initial training session.
      Overall, children's scores improved with training. Memory span was a significant
      predictor of improvement, even after taking into account performance on training
      session 1. Unlike the grammar-matched controls, children with SLI showed greater
      accuracy with repeated sentences compared with unique sentences. Training did not
      improve children's performance on a standardized test of receptive grammar.
      Discussion. Overall, these results indicate that a subset of children with SLI
      perform well below ceiling on reversible sentences with three key words and
      simple syntactic structure. For these children, weak verbal short-term memory
      appears to impair comprehension of spoken sentences. In contrast to the general
      finding that rule-learning benefits from variable input, these children seem to
      do best if given repeated exposure to the same nouns used with a given sentence
      frame. Generalisation to other sentences using the same syntactic frame may be
      more effective if preceded by such item-specific learning. 

PMID- 25392758
TI  - Prior mating success can affect allocation towards future sexual signaling in
      crickets.
AB  - Fitness is often correlated with the expression level of a sexually selected
      trait. However, sexually selected traits are costly to express such that
      investment in their expression should be optimised to maximize their overall
      fitness gains. Social interactions, in the form of successful and unsuccessful
      matings, may offer males one type of feedback allowing them to gauge how to
      allocate their resources towards sexual signaling. Here we tested whether adult
      male black field crickets (Teleogryllus commodus) modify the extent of their
      calling effort (the sexually selected trait) in response to successful and
      unsuccessful matings with females. To examine the effect that mating interactions
      with females have on investment into sexual signaling, we monitored male calling
      effort after maturation and then provided males with a female at two points
      within their life, manipulating whether or not males were able to successfully
      mate each time. Our results demonstrate that males alter their investment towards
      sexual signaling in response to successful matings, but only if the experience
      occurs early in their life. Males that mated early decreased their calling effort
      sooner than males that were denied a mating. Our results demonstrate that social
      feedback in the form of successful and unsuccessful matings has the potential to
      alter the effort a male places towards sexual signaling. 

PMID- 25392760
TI  - Jumping performance in the highly aquatic frog, Xenopus tropicalis: sex-specific
      relationships between morphology and performance.
AB  - Frogs are characterized by a morphology that has been suggested to be related to
      their unique jumping specialization. Yet, the functional demands associated with
      jumping and swimming may not be that different as suggested by studies with semi
      aquatic frogs. Here, we explore whether features previously identified as
      indicative of good burst swimming performance also predict jumping performance in
      a highly aquatic frog, Xenopus tropicalis. Moreover, we test whether the
      morphological determinants of jumping performance are similar in the two sexes
      and whether jumping performance differs in the two sexes. Finally we test whether
      jumping capacity is positively associated with burst swimming and terrestrial
      endurance capacity in both sexes. Our results show sex-specific differences in
      jumping performance when correcting for differences in body size. Moreover, the
      features determining jumping performance are different in the two sexes. Finally,
      the relationships between different performance traits are sex-dependent as well
      with females, but not males, showing a trade-off between peak jumping force and
      the time jumped to exhaustion. This suggests that different selective pressures
      operate on the two sexes, with females being subjected to constraints on
      locomotion due to their greater body mass and investment in reproductive
      capacity. In contrast, males appear to invest more in locomotor capacity giving
      them higher performance for a given body size compared to females. 

PMID- 25392759
TI  - Ancestry-informative markers for African Americans based on the Affymetrix Pan
      African genotyping array.
AB  - Genetic admixture has been utilized as a tool for identifying loci associated
      with complex traits and diseases in recently admixed populations such as African
      Americans. In particular, admixture mapping is an efficient approach to
      identifying genetic basis for those complex diseases with substantial racial or
      ethnic disparities. Though current advances in admixture mapping algorithms may
      utilize the entire panel of SNPs, providing ancestry-informative markers (AIMs)
      that can differentiate parental populations and estimate ancestry proportions in
      an admixed population may particularly benefit admixture mapping in studies of
      limited samples, help identify unsuitable individuals (e.g., through genotyping
      the most informative ancestry markers) before starting large genome-wide
      association studies (GWAS), or guide larger scale targeted deep re-sequencing for
      determining specific disease-causing variants. Defining panels of AIMs based on
      commercial, high-throughput genotyping platforms will facilitate the utilization
      of these platforms for simultaneous admixture mapping of complex traits and
      diseases, in addition to conventional GWAS. Here, we describe AIMs detected based
      on the Shannon Information Content (SIC) or Fst for African Americans with genome
      wide coverage that were selected from ~2.3 million single nucleotide
      polymorphisms (SNPs) covered by the Affymetrix Axiom Pan-African array, a newly
      developed genotyping platform optimized for individuals of African ancestry. 

PMID- 25392761
TI  - Microsatellite frequencies vary with body mass and body temperature in mammals,
      suggesting correlated variation in mutation rate.
AB  - Substitution rate is often found to correlate with life history traits such as
      body mass, a predictor of population size and longevity, and body temperature.
      The underlying mechanism is unclear but most models invoke either natural
      selection or factors such as generation length that change the number of mutation
      opportunities per unit time. Here we use published genome sequences from 69
      mammals to ask whether life history traits impact another form of genetic
      mutation, the high rates of predominantly neutral slippage in microsatellites. We
      find that the length-frequency distributions of three common dinucleotide motifs
      differ greatly between even closely related species. These frequency differences
      correlate with body mass and body temperature and can be used to predict the
      phenotype of an unknown species. Importantly, different length microsatellites
      show complicated patterns of excess and deficit that cannot be explained by a
      simple model where species with short generation lengths have experienced more
      mutations. Instead, the patterns probably require changes in mutation rate that
      impact alleles of different length to different extents. Body temperature
      plausibly influences mutation rate by modulating the propensity for slippage.
      Existing hypotheses struggle to account for a link between body mass and mutation
      rate. However, body mass correlates inversely with population size, which in turn
      predicts heterozygosity. We suggest that heterozygote instability, HI, the idea
      that heterozygous sites show increased mutability, could provide a plausible link
      between body mass and mutation rate. 

PMID- 25392762
TI  - Structural models for the design of novel antiviral agents against Greek Goat
      Encephalitis.
AB  - The Greek Goat Encephalitis virus (GGE) belongs to the Flaviviridae family of the
      genus Flavivirus. The GGE virus constitutes an important pathogen of livestock
      that infects the goat's central nervous system. The viral enzymes of GGE,
      helicase and RNA-dependent RNA polymerase (RdRP), are ideal targets for inhibitor
      design, since those enzymes are crucial for the virus' survival, proliferation
      and transmission. In an effort to understand the molecular structure underlying
      the functions of those viral enzymes, the three dimensional structures of GGE NS3
      helicase and NS5 RdRP have been modelled. The models were constructed in silico
      using conventional homology modelling techniques and the known 3D crystal
      structures of solved proteins from closely related species as templates. The
      established structural models of the GGE NS3 helicase and NS5 RdRP have been
      evaluated for their viability using a repertoire of in silico tools. The goal of
      this study is to present the 3D conformations of the GGE viral enzymes as
      reliable structural models that could provide the platform for the design of
      novel anti-GGE agents. 

PMID- 25392763
TI  - Naive prey exhibit reduced antipredator behavior and survivorship.
AB  - Prey naivete has been hypothesized to be one of the major driving forces behind
      population declines following the introduction of novel predators or release of
      inexperienced prey into predator rich environments. In these cases, naive prey
      may lack sufficient antipredator behavior and, as a result, suffer increased
      mortality. Despite this, some evidence suggests that many prey utilize a
      generalized response to predators. Here, the naivete hypothesis is tested using a
      predator-prey pair sharing an evolutionary history: the red swamp crayfish
      (Procambarus clarkii Girard, 1852) and largemouth bass (Micropterus salmoides
      Lacepede, 1802). Using farm-reared, naive crayfish and wild-caught, experienced
      individuals, laboratory experiments demonstrated that naive, farmed crayfish lack
      behavioral responses to chemical cues from bass, both in terms of movement and
      use of structural refuge. In contrast, experienced crayfish responded strongly to
      the same cues. In a subsequent field tethering experiment, these naive
      individuals suffered a three-fold increase in predation rate. Based on these
      results, recognition of predators may not be innate in all prey, and previous
      experience and learning likely play a key role in the development of antipredator
      behavior. 

PMID- 25392764
TI  - Summary of the IADR Cariology Research, Craniofacial Biology, and Mineralized
      Tissue Groups Symposium, Iguacu Falls, Brazil, June 2012: Gene-environment
      Interactions and Epigenetics in Oral Diseases: Enamel Formation and its Clinical
      Impact on Tooth Defects, Caries, and Erosion.
AB  - Characteristics of enamel may influence or modulate individual susceptibility to
      caries and erosion. These characteristics are defined during development, which
      is under strict genetic control, but can easily be modified in many ways by
      environmental factors. In the symposium, translational aspects of embryology,
      biochemistry, and genetics of amelogenesis were presented. The symposium provided
      unique insight into how basic sciences integrate with clinically relevant
      problems. The need for improved understanding of risks at the individual level,
      taking into consideration both environmental exposures and genetic background,
      was presented. The symposium was divided into four stepwise and interconnected
      topics as follows: 1) The Many Faces of Enamel Development; 2) Enamel
      Pathogenesis: Biochemistry Lessons; 3) Environmental Factors on Enamel Formation;
      and, 4) Genetic Variation in Enamel Formation Genes.

PMID- 25392766
TI  - Foreword.

PMID- 25392765
TI  - Increased vitamin D is associated with decline of naive, but accumulation of
      effector, CD8 T cells during early aging.
AB  - Given the protective roles of 25-hydroxyvitamin D (25[OH]D or vitamin D) in
      musculoskeletal health and the potential beneficial effects of vitamin D
      supplementation in reducing the risk of various chronic diseases, intensive
      repletion of vitamin D has been widely advocated. Of note, CD8 T cells have the
      highest levels of the vitamin D receptor compared with other major immune cells.
      The effects of vitamin D on CD8 T cells during aging, however, remain unclear.
      This study determined the relationship between vitamin D levels and CD8 T-cell
      status in 34 healthy female subjects (all >60 years old). The CD8 T cell
      phenotype was defined by the surface expression of CD28 and CD95. The low-25(OH)D
      serum groups (<=30 ng/ml) had higher percentages of CD28+CD95-CD8+ (naive) T
      cells and lower percentages of CD28+CD95+CD8+ (effector) T cells. By contrast,
      subjects with high levels of 25(OH)D had very low percentages of naive CD8 T
      cells but very high percentages of effector CD8 T cells. There was a significant
      inverse correlation between 25(OH)D levels and the frequency of naive CD8 T
      cells. The results show that higher levels of vitamin D are correlated with
      decreased frequencies of naive CD8 T cells during early aging, suggesting that
      higher levels of 25(OH)D accelerate CD8 T-cell senescence. These results warrant
      the further evaluation of the effects of vitamin D supplementation in immune
      aging.

PMID- 25392767
TI  - Vertex collocation profiles: theory, computation, and results.
AB  - We describe the vertex collocation profile (VCP) concept. VCPs provide rich
      information about the surrounding local structure of embedded vertex pairs. VCP
      analysis offers a new tool for researchers and domain experts to understand the
      underlying growth mechanisms in their networks and to analyze link formation
      mechanisms in the appropriate sociological, biological, physical, or other
      context. The same resolution that gives the VCP method its analytical power also
      enables it to perform well when used to accomplish link prediction. We first
      develop the theory, mathematics, and algorithms underlying VCPs. We provide
      timing results to demonstrate that the algorithms scale well even for large
      networks. Then we demonstrate VCP methods performing link prediction
      competitively with unsupervised and supervised methods across different network
      families. Unlike many analytical tools, VCPs inherently generalize to
      multirelational data, which provides them with unique power in complex modeling
      tasks. To demonstrate this, we apply the VCP method to longitudinal networks by
      encoding temporally resolved information into different relations. In this way,
      the transitions between VCP elements represent temporal evolutionary patterns in
      the longitudinal network data. Results show that VCPs can use this additional
      data, typically challenging to employ, to improve predictive model accuracies. We
      conclude with our perspectives on the VCP method and its future in network
      science, particularly link prediction. 

PMID- 25392768
TI  - Application of the SP theory of intelligence to the understanding of natural
      vision and the development of computer vision.
AB  - ABSTRACT: The SP theory of intelligence aims to simplify and integrate concepts
      in computing and cognition, with information compression as a unifying theme.
      This article is about how the SP theory may, with advantage, be applied to the
      understanding of natural vision and the development of computer vision. Potential
      benefits include an overall simplification of concepts in a universal framework
      for knowledge and seamless integration of vision with other sensory modalities
      and other aspects of intelligence. Low level perceptual features such as edges or
      corners may be identified by the extraction of redundancy in uniform areas in the
      manner of the run-length encoding technique for information compression. The
      concept of multiple alignment in the SP theory may be applied to the recognition
      of objects, and to scene analysis, with a hierarchy of parts and sub-parts, at
      multiple levels of abstraction, and with family-resemblance or polythetic
      categories. The theory has potential for the unsupervised learning of visual
      objects and classes of objects, and suggests how coherent concepts may be derived
      from fragments. As in natural vision, both recognition and learning in the SP
      system are robust in the face of errors of omission, commission and substitution.
      The theory suggests how, via vision, we may piece together a knowledge of the
      three-dimensional structure of objects and of our environment, it provides an
      account of how we may see things that are not objectively present in an image,
      how we may recognise something despite variations in the size of its retinal
      image, and how raster graphics and vector graphics may be unified. And it has
      things to say about the phenomena of lightness constancy and colour constancy,
      the role of context in recognition, ambiguities in visual perception, and the
      integration of vision with other senses and other aspects of intelligence.

PMID- 25392770
TI  - Hidden gout- Ultrasound findings in patients with musculo-skeletal problems and
      hyperuricemia.
AB  - The goal of this study was to investigate the frequency of gout-specific
      ultrasonography findings in a cohort of hyperuricemic patients with various
      musculo-skeletal complaints. A blinded examiner regarding the patients' clinical
      and laboratory assessment performed standardized ultrasound examinations of 12
      joints in 74 individuals with diverse musculo-skeletal complaints. Gout-specific
      changes were assessed and combined with the patients' medical history (diagnosis
      gout vs. non-gout) and laboratory values of hyperuricemia. Of 74 patients, 58
      (mean age 55 yrs) had hyperuricemia (serum uric acid levels > 7 mg/dl/420
      MUmol/L). Of those, 27 (47%) had a history of gout attacks. In total, 888 joints
      were examined by ultrasound. With 44/324 joints (14%) the pathological finding
      most often found in joints of gout patients was the double contour sign compared
      to 29/372 joints (8%) in patients with asymptomatic hyperuricemia and 2/192
      joints (1%) in normouricemic controls. In patients with gout, the ultrasound
      showed pathological findings in 67/324 joints (21%). In 26/39 (67%) previously
      affected joints, gout-specific sonographic indications were found. With regard to
      the first metatarsophalangeal joint, sonographic pathologies were detectable in
      16/22 (73%) so far asymptomatic joints on the contralateral. Ultrasonographic
      gout-specific signs are not only found in joints affected by gout attacks, but
      often also in the corresponding contralateral, asymptomatic joint. Patients with
      asymptomatic hyperuricemia already showed sonographic features implicating an as
      yet "silent" precipitation of urate crystals. As the examined cohort represents
      patients at high risk, further research for gout-specific findings is indicated,
      especially for hyperuricemic patients. 

PMID- 25392769
TI  - An approach for aggregating upstream catchment information to support research
      and management of fluvial systems across large landscapes.
AB  - The growing quality and availability of spatial map layers (e.g., climate,
      geology, and land use) allow stream studies, which historically have occurred
      over small areas like a single watershed or stream reach, to increasingly explore
      questions from a landscape perspective. This large-scale perspective for fluvial
      studies depends on the ability to characterize influences on streams resulting
      from throughout entire upstream networks or catchments. While acquiring upstream
      information for a single reach is relatively straight-forward, this process
      becomes demanding when attempting to obtain summaries for all streams throughout
      a stream network and across large basins. Additionally, the complex nature of
      stream networks, including braided streams, adds to the challenge of accurately
      generating upstream summaries. This paper outlines an approach to solve these
      challenges by building a database and applying an algorithm to gather upstream
      landscape information for digitized stream networks. This approach avoids the
      need to directly use spatial data files in computation, and efficiently and
      accurately acquires various types of upstream summaries of landscape information
      across large regions using tabular processing. In particular, this approach is
      not limited to the use of any specific database software or programming language,
      and its flexibility allows it to be adapted to any digitized stream network as
      long as it meets a few minimum requirements. This efficient approach facilitates
      the growing demand of acquiring upstream summaries at large geographic scales and
      helps to support the use of landscape information in assisting management and
      decision-making across large regions. 

PMID- 25392771
TI  - Nonlinearities distribution Laplace transform-homotopy perturbation method.
AB  - This article proposes non-linearities distribution Laplace transform-homotopy
      perturbation method (NDLT-HPM) to find approximate solutions for linear and
      nonlinear differential equations with finite boundary conditions. We will see
      that the method is particularly relevant in case of equations with nonhomogeneous
      non-polynomial terms. Comparing figures between approximate and exact solutions
      we show the effectiveness of the proposed method. 

PMID- 25392772
TI  - Porosity and distribution of water in perlite from the island of Milos, Greece.
AB  - A perlite sample representative of an operating mine in Milos was investigated
      with respect to the type and spatial distribution of water. A set of different
      methods was used which finally provided a consistent view on the water at least
      in this perlite. Infrared spectroscopy showed the presence of different water
      species (molecular water and hydroxyl groups / strongly bound water). The
      presence of more than 0.5 mass% smectite, however, could be excluded considering
      the cation exchange capacity results. The dehydration measured by thermal
      analysis occurred over a wide range of temperatures hence confirming the infrared
      spectroscopical results. Both methods point to the existence of a continuous
      spectrum of water binding energies. The spatial distribution of water and/or
      pores was investigated using different methods (CT: computer tomography, FIB:
      scanning electron microscopy including focused ion beam technology, IRM: infrared
      microscopy). Computer tomography (CT) showed large macropores (20 - 100 MUm) and
      additionally revealed a mottled microstructure of the silicate matrix with low
      density areas up to a few MUm in diameter. Scanning electron microscopy (FIB)
      confirmed the presence of MUm sized pores and IRM showed the filling of these
      pores with water. In summary, two types of pores were found. Airfilled 20 - 100
      MUm pores and MUm-sized pores disseminated in the glass matrix containing at
      least some water. Porosity measurements indicate a total porosity of 26 Vol%, 11
      Vol% corresponding to the MUm-sized pores. It remains unsolved wether the water
      in the MUm-sized pores entered after or throughout perlite formation. However,
      the pores are sealed and no indications of cracks were found which indicated a
      primary source of the water, i.e. water was probably entrapped by quenching of
      the lava. The water in these pores may be the main reason for the thermal
      expandability which results in the extraordinarily porous expanded perlite
      building materials. 

PMID- 25392773
TI  - Peptaibols from Trichoderma asperellum TR356 strain isolated from Brazilian soil.
AB  - The Trichoderma genus consists of a group of free-living filamentous fungi,
      including species able to act as biological control agents (BCAs) against
      pathogenic fungi. It is believed that this ability is due to synergy between
      several mechanisms, including the production of a wide variety of secondary
      metabolites by these organisms. Among these, we highlight the production of
      peptaibols, an antibiotic peptide group characterized by the presence of non
      proteinogenic amino acids such as alpha-aminoisobutyrate (Aib), as well as by N
      terminal modifications and amino alcohols in the C-terminal region. This study
      aimed to outline a profile of peptaibol production and to identify secreted
      peptaibols from the Trichoderma asperellum TR356 strain, described as an
      efficient BCA against S. sclerotiorum. The fungus was grown on TLE 0.3% glucose
      medium for 5 days, with agitation at 120 rpm in the dark. Liquid medium filtrate
      was used as the metabolite source. These extracts were subjected to high
      performance liquid chromatography (HPLC) and subsequent analysis by matrix
      assisted laser desorption ionization mass spectrometry (MALDI-TOF). The results
      indicate the production of two classes of peptaibols for this T. asperellum
      strain. Primary structures of two asperelines (A and E) and five trichotoxins
      (T5D2, T5E, T5F, T5G and 1717A) have been elucidated. Most of these peptaibols
      had been previously described in T. viride and T. asperellum marine strains. This
      is the first report of some of these compounds being produced by a T. asperellum
      strain from soil. Future analyses will be necessary to elucidate the three
      dimensional structures and their activities against pathogens. 

PMID- 25392774
TI  - Situs inversus totalis with congenitally corrected transposition of the great
      arteries: insights from cardiac MRI.
AB  - INTRODUCTION: Situs inversus totalis with congenitally corrected transposition of
      the great arteries represents a relatively rare congenital condition. CASE
      DESCRIPTION: The current report describes the case of a 56 year old patient with
      an atrio-ventricular and ventricular-arterial discordance of the heart chambers
      without surgical correction, incidentally detected during hepatocellular
      carcinoma evaluation. The systemic venous blood arrived via the right atrium and
      a mitral valve in the morphologically left but pulmonary arterial ventricle that
      gave rise to a pulmonary trunk. The pulmonary venous blood passed the left atrium
      and the tricuspid valve into a morphologically right but systemic ventricle that
      gave rise to the aorta. DISCUSSION AND EVALUATION: The switched anatomy was
      incidentally detected on echocardiography. The patient was referred to cardiac
      magnetic resonance imaging (CMR) including flow measurements, volumetry and late
      enhancement. CMR results showed a mildly impaired function and the switched
      anatomy. During a follow-up period of 2 years the patient was suffering from only
      mild heart failure and dyspnea. CONCLUSIONS: Heart failure symptoms and
      arrhythmias can appear with increasing age in patients with congenitally
      corrected transposition. Early CMR allows accurate diagnosis and timely
      introduction of adequate therapy thereby avoiding disease progression.

PMID- 25392775
TI  - Selective versus comprehensive emergency management in Korea.
AB  - In spite of Korean governments' efforts, many emergency management practitioners
      wonder whether what is actually being practiced is selective or comprehensive
      management. Using a qualitative content analysis and experiences in practice, the
      article analyzes the barriers to selective emergency management and the paths to
      comprehensive emergency management via the same three management elements:
      stakeholders, phases of the emergency management lifecycle, and hazards and
      impacts. Four analytical levels are considered: central government level,
      industry level, community level, and household level. Korea, despite its self
      praise, has to transform its selective emergency management into comprehensive
      emergency management in time. 

PMID- 25392777
TI  - The influence of acute hypoxic exposure on isokinetic muscle force production.
AB  - To investigated whether an acute hypoxic stimulus affects muscle strength
      development assessed by isokinetic dynamometry during maximal knee extension. A
      total of 15 healthy young men participated in this study (61.9 +/- 6.1 kg; 1.72
      +/- 0.08 m; 20.9 +/- 2.6 years). We evaluated knee extension and flexion
      isokinetic dynamometer performance in normoxic and hypoxic conditions. The
      analyzed parameters, for concentric contraction, were peak torque and total work
      measured at 1.05 and 5.23 rad/s; and fatigue index measured at 5.23 rad/s. During
      isokinetic testing, heart rate and oxygen saturation (SpO2) were monitored.
      Hypoxic conditions (3,600 m) were simulated, via a mixing chamber, with the
      dilution being constantly controlled by a PO2 probe. Test reproducibility results
      (test-retest) for all isokinetic knee parameters were classified as moderate to
      almost perfect (ICC = 0.694 to 0.932). SpO2 was 88.4 +/- 3.4% in the hypoxic
      condition and 97.1 +/- 0.7% in the normoxic condition (p = 0.000, effect size =
      0.87). Heart rate was not significantly different between normoxic and hypoxic
      conditions at the end of the test. There were no significant differences in
      isokinetic variables evaluated for the extensor and flexor muscles at concentric
      contraction between the normoxic and hypoxic conditions. Our findings indicate
      that reduced arterial oxygenation per se has no effect on the muscular isokinetic
      strength of the knee extensors. 

PMID- 25392776
TI  - Gastrointestinal comorbidities associated with atrial fibrillation.
AB  - This observational study was conducted to describe the risk of gastrointestinal
      (GI) events among patients with atrial fibrillation (AF). We analyzed Thomson
      Reuters MarketScan(r) data from 2005 to 2009. Subjects aged >=18 years with >= 1
      AF diagnosis were selected. GI events were identified from claims with a primary
      or secondary diagnosis code for any GI condition. The risk of GI events was
      assessed using cumulative incidence (new GI events/patients with AF without GI
      condition at baseline) and incidence rates (IRs), calculated as the number of
      patients with new GI events divided by patient-years of observation. In addition,
      the CHADS2 score was evaluated at baseline to determine the patient's risk of
      stroke. A total of 557,123 AF patients were identified. The mean (median) AF
      patient age was 68.2 years (70); 45% were female. The cumulative incidences of
      any GI event and dyspepsia were 40% and 19%, respectively. The corresponding IRs
      were 38.8 and 14.7 events per 100 patient-years. IRs of any GI events for female
      and male patients were 43.6 and 35.5; for patients in the age groups <65, 65-74,
      75-84, and >=85 years, IRs were 32.3, 38.9, 44.6, and 52.7; for patients with a
      CHADS2 score of 0, 1-2, 3-4, and 5-6, IRs were 30.3, 41.6, 56.9, and 74.5,
      respectively. In this large claims database, 40% of AF patients experienced a GI
      event, predominantly dyspepsia. Physicians should take age and comorbidities into
      consideration when managing AF patients. 

PMID- 25392778
TI  - Arthritis Robustus: review of a case of an "abnormal" rheumatoid.
AB  - INTRODUCTION: Incidental discovery or diagnosis of Rheumatoid Arthritis where the
      patient remains blissfully unaware of his affection is a rare occurrence. CASE
      DESCRIPTION: We present the case of a telephone wireman in whom Rheumatoid
      Arthritis neither affected his activities of daily living nor caused any
      deformity to develop. It remained asymptomatic till its incidental discovery
      during his admission for treatment of myocardial infarction. DISCUSSION AND
      EVALUATION: This presentation of Rheumatoid Arthritis is termed 'Arthritis
      Robustus' and goes against the very tenets of the picture of Rheumatoid Arthritis
      we have in our minds. The name given to this entity stems from the fact that
      these patients are mostly physical labourers i.e. 'Robust'. CONCLUSION:
      Rheumatoid Arthritis can very rarely be asymptomatic. The rarity of the entity
      can be inferred from the paucity of published literature.

PMID- 25392779
TI  - Imaging findings of primary hepatic carcinoid tumor with an emphasis on MR
      imaging: case study.
AB  - Carcinoid tumors are slow-growing tumors originating in the neuroendocrine cells,
      and occur most frequently within the gastrointestinal tract. Although the liver
      is the most common site for metastatic carcinoid tumors, primary hepatic
      carcinoid tumors are exceedingly rare and reports of the imaging findings have
      been very scarce. We herein report imaging findings with an emphasis on magnetic
      resonance imaging in two cases of primary hepatic carcinoid tumors. In both
      cases, the tumors showed cystic areas with hemorrhagic components and early
      enhanced solid areas. 

PMID- 25392780
TI  - Physiological alterations after a marathon in the first 90-year-old male
      finisher: case study.
AB  - INTRODUCTION: Endurance performance decreases during ageing due to alterations in
      physiological characteristics, energy stores, and psychological factors. To
      investigate alterations in physiological characteristics and body composition of
      elderly master athletes in response to an extreme endurance event, we present the
      case of the first ninety-year-old official male marathon finisher. CASE
      DESCRIPTION: Before and directly after the marathon, a treadmill incremental
      test, dual-energy X-ray absorptiometry, peripheral quantitative computed
      tomography, mechanography, and dynamometry measurements were conducted. The
      athlete finished the marathon in 6 h 48 min 55 s, which corresponds to an average
      competition speed of 6.19 km h(-1). DISCUSSION AND EVALUATION: Before the
      marathon, [Formula: see text] was 31.5 ml min(-1) kg(-1) body mass and peak heart
      rate was 140 beats min(-1). Total fat mass increased in the final preparation
      phase (+3.4%), while leg fat mass and leg lean mass were slightly reduced after
      the marathon (-3.7 and -1.6%, respectively). Countermovement jump (CMJ) peak
      power and peak velocity decreased after the marathon (-16.5 and -14.7%,
      respectively). Total impulse during CMJ and energy cost of running were not
      altered by the marathon. In the left leg, maximal voluntary ground reaction force
      (F m1LH) and maximal isometric voluntary torque (MIVT) were impaired after the
      marathon (-12.2 and -14.5%, respectively). CONCLUSIONS: Side differences in F
      m1LH and MIVT could be attributed to the distinct non-symmetrical running pattern
      of the athlete. Similarities in alterations in leg composition and CMJ
      performance existed between the nonagenarian athlete and young marathon runners.
      In contrast, alterations in total body composition and m1LH performance were
      markedly different in the nonagenarian athlete when compared to his younger
      counterparts.

PMID- 25392781
TI  - HCC surveillance results in earlier HCC detection: results from an Indian cohort.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related
      death worldwide, with an increased incidence in South Asia. In order to describe
      the effect of surveillance for HCC with biannual ultrasound and alpha-fetoprotein
      (AFP) on diagnosis and survival in an Indian population a retrospective cohort
      control study was performed at two liver clinics in India. The medical records of
      3,258 patients with cirrhosis who received surveillance for HCC were reviewed,
      and 100 patients who developed HCC identified. Sixty-four cirrhotic patients
      diagnosed with HCC during the same time period without a history of surveillance
      were included and survival, BCLC stage at diagnosis, and treatment were compared.
      Patients who underwent surveillance were more likely to be diagnosed with
      potentially curable or treatable BCLC Stage 0/A disease and Stage B/C disease
      respectively, than late Stage D disease (chi2 = 0.0007). Patients diagnosed at an
      earlier stage of HCC lived significantly longer after diagnosis than patients
      diagnosed at a later stage (Stage 0/A: 15.6 +/- 14.2 months vs. Stage B/C: 9.43
      +/- 19.7 months vs. Stage D: 5.59 +/- 11.9 months; p = 0.0006). While treatment
      for HCC improved overall survival, only 28% of eligible patients received
      treatment, explaining the lack of survival benefit noted in the surveillance
      group. Surveillance for HCC led to detection of HCC at earlier stages. The impact
      of surveillance on improved mortality could not be evaluated given the limited
      number of patients who received treatment. HCC surveillance has the potential to
      improve survival in South Asian patients with cirrhosis only if improvements in
      access to appropriate treatment are made. 

PMID- 25392782
TI  - The factors that limit activities of certified diabetes educators in Japan: a
      questionnaire survey.
AB  - BACKGROUND: The certified diabetes educator (CDE) is a qualification awarded to
      health professionals with specialized knowledge, skills, and experiences in
      diabetes management and education. To clarify whether CDEs consider themselves to
      be working sufficiently, in other words, making sufficient use of their
      specialized skills or not, a questionnaire survey was conducted. The participants
      were persons involved in diabetes-related educational seminars and medical
      personnel engaged in diabetes care at the National Center for Global Health and
      Medicine. They were asked to complete a questionnaire regarding self -perception
      of CDE's activities and to describe the reasons for their answers. FINDINGS:
      Fewer than 40% of the responding CDEs in each of the professions surveyed were
      satisfied with the current state of their activities and contributions as a CDE.
      For CDEs, "lack of labor" is the most concerning issue that limits their
      satisfactory activities as CDEs, followed by "condition of facilities". Other
      factors such as insufficient "interprofessional teamwork", "limited personal
      ability", "mismatched allocation", and "low recognition for CDEs" also limited
      their activities. CONCLUSION: Many CDEs perceived they are not working
      sufficiently. Further efforts should be made to support CDEs to improve their
      working conditions.

PMID- 25392783
TI  - Metabolic syndrome and its components in patients with psoriasis.
AB  - Psoriasis is a chronic inflammatory disease of the skin which affects 1-3% of the
      population. A higher association of metabolic syndrome (MS) has been described
      amongst sufferers. The objective of this study was to assess the association of
      MS and its components amongst subjects suffering psoriasis and compare it with
      that found for the control group. The secondary objective was to study the
      relationship between the duration and severity of the psoriasis and the MS. This
      was a case-control study: 102 subjects with psoriasis and 102 control subjects
      paired by sex, age and body mass index. Anamnesis: history of diabetes mellitus,
      arterial hypertension, dyslipidaemia and psoriasis. Lifestyle. PHYSICAL
      EXAMINATION: weight, height, blood pressure, waist circumference. TESTS: lipid
      profile, oral glucose tolerance test and insulinemia (HOMA calculation). MS
      classified according to the 2009 consensus. The prevalence of MS amongst
      psoriasis patients was 52.9%, as compared to 34.31% in the control group. MS
      independent factors: age (OR 1.085), body mass index (OR 1.346), sex (OR 2.69 for
      men) and psoriasis (OR 3.634). A comparative study of patients with psoriasis
      with or without MS, revealed no relationship to the severity, age at time of
      diagnosis or time of evolution of the psoriasis. In conclusion, the association
      of MS amongst psoriasis sufferers is very high and the disease is considered as
      an independent risk factor for MS. Our results show no relationship between the
      different characteristics of psoriasis and the presence of MS. The main
      limitation of this study is that it does not enable to conclude whether psoriasis
      is a risk factor for MS or the opposite.

PMID- 25392784
TI  - Quantitative RT-PCR analysis of differentially expressed genes in Quercus suber
      in response to Phytophthora cinnamomi infection.
AB  - cDNA-AFLP methodology was used to gain insight into gene fragments differentially
      present in the mRNA profiles of Quercus suber roots infected with zoospores of
      Phytophthora cinnamomi at different post challenge time points. Fifty-three
      transcript-derived fragments (TDFs) were identified and sequenced. Six candidate
      genes were selected based on their expression patterns and homology to genes
      known to play a role in defence. They encode a cinnamyl alcohol dehydrogenase2
      (QsCAD2), a protein disulphide isomerase (QsPDI), a CC-NBS-LRR resistance protein
      (QsRPc), a thaumatin-like protein (QsTLP), a chitinase (QsCHI) and a 1,3-beta
      glucanase (QsGlu). Evaluation of the expression of these genes by quantitative
      polymerase chain reaction (qPCR) revealed that transcript levels of QsRPc, QsCHI,
      QsCAD2 and QsPDI increased during the first 24 h post-inoculation, while those of
      thaumatin-like protein decreased. No differential expression was observed for 1,3
      beta-glucanase (QsGlu). Four candidate reference genes, polymerase II (QsRPII),
      eukaryotic translation initiation factor 5A (QsEIF-5A), beta-tubulin (QsTUB) and
      a medium subunit family protein of clathrin adaptor complexes (QsCACs) were
      assessed to determine the most stable internal references for qRT-PCR
      normalization in the Phytophthora-Q. suber pathosystem in root tissues. Those
      found to be more stable, QsRPII and QsCACs, were used as internal reference in
      the present work. Knowledge on the Quercus defence mechanisms against biotic
      stress is scarce. This study provides an insight into the gene profiling of a few
      important genes of Q. suber in response to P. cinnamomi infection contributing to
      the knowledge of the molecular interactions involving Quercus and root pathogens
      that can be useful in the future to understand the mechanisms underlying oak
      resistance to soil-borne oomycetes. 

PMID- 25392785
TI  - Sequence exploration reveals information bias among molecular markers used in
      phylogenetic reconstruction for Colletotrichum species.
AB  - The Colletotrichum gloeosporioides species complex is among the most destructive
      fungal plant pathogens in the world, however, identification of isolates of
      quarantine importance to the intra-specific level is confounded by a number of
      factors that affect phylogenetic reconstruction. Information bias and quality
      parameters were investigated to determine whether nucleotide sequence alignments
      and phylogenetic trees accurately reflect the genetic diversity and phylogenetic
      relatedness of individuals. Sequence exploration of GAPDH, ACT, TUB2 and ITS
      markers indicated that the query sequences had different patterns of nucleotide
      substitution but were without evidence of base substitution saturation. Regions
      of high entropy were much more dispersed in the ACT and GAPDH marker alignments
      than for the ITS and TUB2 markers. A discernible bimodal gap in the genetic
      distance frequency histograms was produced for the ACT and GAPDH markers which
      indicated successful separation of intra- and inter-specific sequences in the
      data set. Overall, analyses indicated clear differences in the ability of these
      markers to phylogenetically separate individuals to the intra-specific level
      which coincided with information bias. 

PMID- 25392786
TI  - Carbon nanodots interference with lactate dehydrogenase assay in human monocyte
      THP-1 cells.
AB  - BACKGROUND: Carbon nanodots (CD), a new class of carbon nanomaterials with sizes
      below 10 nm, have recently attracted wide attention due to their superiority in
      water solubility, chemical inertness, and resistance to photobleaching. As a
      result, CD has found important and wide applications in energy, catalysis,
      biological labeling, bioimaging and drug delivery. On the other hand, due to the
      lack of available toxicity data, there is a growing concern regarding the
      potential risks of CD. Hence, accurate assessment of the cytotoxicity of CD has
      become more important than ever before. The lactate dehydrogenase (LDH) assay is
      widely used to detect cytotoxicity of various nanoparticles including CD. Many
      recent studies used LDH assay to study the CD toxicity in various cells. However,
      these studies failed to further examine whether the CD were interfering with the
      LDH assay which would alter their findings. FINDINGS: This study investigated the
      possible interference of carbon nanodots on the LDH assay in human monocyte THP-1
      cells. Monocytes are known to be involved in inflammable vascular diseases, and
      have been suggested to be the targets for CD exposure. In this study, the
      cytotoxicity of CD in concentrations ranging from 0.075 to 0.60 mg/mL, was
      determined by using the LDH assay. To validate the results of LDH assay, the cell
      counting method with trypan blue staining was used. With 24 hours incubation
      time, the cell viability of THP-1 was significantly decreased according to the
      trypan blue staining method. Whereas, in the LDH assay, the CD was found to
      interfere in a dose-dependent manner with the NADH absorbance measurements at 340
      nm. CONCLUSIONS: This study represents the first report on the negative
      interference of CD on LDH assay, and caution should be observed when evaluating
      the cytotoxicity of CD.

PMID- 25392787
TI  - Adenomyoma of the small intestine a rare pathological lead point for
      intussusception in an infant.
AB  - INTRODUCTION: Intussusception is a typical abdominal emergency in early
      childhood. CASE DESCRIPTION: We report a case of an infant in the typically
      affected age group with an intussusception triggered by a rare benign intramural
      intestinal adenomyoma as a pathological lead point. The infant had the typical
      symptoms of a recurrent idiopathic ileocolic intussusception. DISCUSSION AND
      EVALUATION: Idiopathic intussusception is frequent in the infant age group.
      Contrary to that, reports on pathological lead points for intussusceptions are
      sparse in the toddler age. CONCLUSIONS: That case illustrates that even in
      intussusceptions in the typically affected age group, it is important to be aware
      of pathological lead points, especially if the intussusceptions are recurrent.

PMID- 25392788
TI  - Identification of nucleotide sequence involved in Weissellicin L production.
AB  - BACKGROUND: Weissellicin L, a novel bacteriocin produced by Weissella hellenica 4
      7, was previously characterized but its full amino acid sequence remain unknown.
      The draft genome sequencing analysis of Weissella hellenica 4-7 was performed and
      the open reading frame (ORF) encoding the weissellicin L was identified and
      clarified. FINDINGS: The obtained results indicated that the mature bacteriocin
      consists of 29 amino acid residues with a molecular weight of approximately
      3205.64 Da. A conserved processing site of two glycine residues in positions -1
      and -2 was observed in the leader peptides. The possibility that bacteriocin
      secretion depended on ATP-binding cassette (ABC) transporter was therefore
      suggested. Furthermore, primers were designed from 5' and 3' flanking sequences
      of the weissellicin L structural gene. PCR presented a single product and was
      useful to detect weissellicin L structural gene. CONCLUSIONS: To our knowledge,
      this is the first report describing the full amino acid sequence of Weissellicin
      L. A rapid method to detect weissellicin L structural gene was also reported in
      this study.

PMID- 25392789
TI  - Vascularity of the urethra in continent women using colour doppler high-frequency
      endovaginal ultrasonography.
AB  - OBJECTIVES: To assess the urethral vascularity in continent women using colour
      doppler high frequency endovaginal ultrasonography (EVUS). METHODS: We recruited
      61 continent women attending gynaecology clinics between July and October 2009.
      Exclusion criteria included symptoms of urinary incontinence, voiding
      dysfunction, pelvic organ prolapse or urinary tract infection. The participants
      underwent EVUS using high frequency (9-12 MHz) biplane transducer (type 8848 BK
      Medical), according to a standardised protocol. Colour Doppler US was performed
      in sagittal plane and in transverse plane at the level of the mid-urethra. Ten
      seconds video files were recorded and following vascular parameters: flow
      velocity (Vmix), area of the vessels (Amix), intensity of vascularity (Imix),
      pulsatility index (PImix) and resistance index (RImix) was evaluated. RESULTS:
      There were 30 nulliparous (49.2%) women and 31 multiparous women (50.8%) with a
      mean (+/-SD) age of 32 (+/-4) and 46 (+/-6) years respectively. Significant
      impairment of vascularity was observed in multiparous patients as compared to
      nulliparous and was reflected by increased values of RImix (p < 0.001) and PImix
      (p < 0.001), and decreased values of Vmix (p < 0.001), Amix (p < 0.001), Imix (p
      < 0.001) in axial and midsagittal sections of the midurethra. A significant
      decrease of mean value +/- SD of Imix- from 0.02 +/- 0.02 in nulliparous to 0.005
      +/- 0.01 in multiparous was observed. Cronbach alpha, used to assess vascular
      correlations and parity demonstrated a reduction when expressed only for vascular
      parameters, indicating that number of deliveries is an important factor while
      assessing urethral vascularity. CONCLUSIONS: Compared to continent nulliparous
      women, continent multiparous women demonstrated a significant reduction in the
      vascularity parameters in all measured variables when parity was accounted for.
      ADVANCES IN KNOWLEDGE: This study provides the basis for further research in
      assessing urethral vascularity in women.

PMID- 25392790
TI  - High-sensitivity troponin T as a marker to predict cardiotoxicity in breast
      cancer patients with adjuvant trastuzumab therapy.
AB  - The humanized monoclonal antibody trastuzumab has been in routine use for
      chemotherapy for human epidermal growth factor receptor II (HER2)-positive breast
      cancer. A major adverse effect of trastuzumab is cardiotoxicity. Well-established
      biomarkers or echocardiographic parameters to predict trastuzumab-induced
      cardiotoxicity have not yet been determined. We attempted to identify useful
      biomarkers and/or echocardiographic parameters to predict trastuzumab-induced
      cardiotoxicity. We prospectively investigated the cases of 19 women who received
      chemotherapy including anthracyclines and trastuzumab for HER2-positive breast
      cancer. We measured cardiac biomarkers and echocardiographic parameters before
      their chemotherapy and every 3 months up to 15 months until the end of the
      adjuvant trastuzumab therapy. We divided the patients into two groups: group R
      was the nine patients who showed a reduction of left ventricular ejection
      fraction (LVEF) >=5%, and group N was the 10 patients who showed a reduction of
      LVEF <5%. The high-sensitivity troponin T (hs-TnT) level at 6 months was
      significantly higher in group R than in group N (11.0 +/- 7.8 pg/mL vs. 4.0 +/-
      1.4 pg/mL, p < 0.01). The hs-TnT level with a cutoff value of 5.5 pg/mL at 6
      months had 78% sensitivity and 80% specificity for predicting a reduction of LVEF
      at 15 months. In our evaluation of echocardiographic parameters at baseline, the
      diastolic function was more impaired in group R than in group N. The hs-TnT and
      echocardiographic parameters of diastolic function could be useful to predict
      trastuzumab-induced cardiotoxicity. 

PMID- 25392791
TI  - The complete alk sequences of Rhodococcus erythropolis from Lake Baikal.
AB  - BACKGROUND: Rhodococci are bacteria able to degrade a wide range of hydrocarbons,
      including the alkanes present in crude oil, due to alk genes in their genomes.
      FINDINGS: Genome sequencing of DNA from Rhodococcus erythropolis strain 4
      (obtained from a deep-water bitumen mound) revealed four alk genes, and the
      predicted amino acid sequences coded by these genes were highly conserved, having
      sections up to 11 amino acid residues. CONCLUSIONS: Obtained four genes from
      Rhodococcus erythropolis were similar to corresponding genes from other bacteria
      collected from other environments, including marine sources. This indicated a
      large-scale horizontal alk gene transfer between bacteria from different
      subgenera.

PMID- 25392792
TI  - Characterization of Actinomycetes and Trichoderma spp. for cellulase production
      utilizing crude substrates by response surface methodology.
AB  - Laboratory bench scaling was done and an average of 1.85 fold increase by
      Response Surface Methodology (RSM) optimization was obtained. It was found that
      the predicted value (4.96 IU/ml) obtained by RSM is in close accordance with
      observed activity 5.14 IU/ml. Endoglucanases are mainly induced by CMC while
      Wheat bran (natural substrate) exoglucanase is more active when induced by avicel
      and cellulose. Addition of substrate beyond a level caused inhibition of
      cellulase production. The molecular weight of protein as determined by SDS-PAGE
      is very similar to molecular weight of cellulase of Trichoderma viride (T.
      viride) cellulase and Trichoderma reesei (T. reesei) endoglucanase. T. reesei
      beta-glucosidase has high enzymatic activity on CMC substrate when compared with
      T. viride beta-glucosidase. Secondary structure analysed by using Circular
      Dichroism confirmed that composition of celluase system is very similar to other
      analysed species. The cellulase was found to be active in pH range of 4.8-5.5;
      while temperature range varied from 50 degrees C to 70 degrees C. Although the
      enzymatic activity produced by mutants were lesser than the parent, but in one
      case mutants of Trichoderma reesei's BGL has shown higher activity on cellulose. 

PMID- 25392793
TI  - Sequence of inequalities among fuzzy mean difference divergence measures and
      their applications.
AB  - This paper presents a sequence of fuzzy mean difference divergence measures. The
      validity of these fuzzy mean difference divergence measures is proved
      axiomatically. In addition, it introduces a sequence of inequalities among some
      of these fuzzy mean difference divergence measures. The applications of proposed
      fuzzy mean difference divergence measures in the context of pattern recognition
      have been presented using a numerical example. It is shown that the proposed
      fuzzy mean difference divergence measures are well suited to use with linguistic
      variables. Finally, on establishing inequalities, we find that our proposed
      measures are computationally much more efficient. 

PMID- 25392794
TI  - Measurement of muscle length-related electromyography activity of the hip flexor
      muscles to determine individual muscle contributions to the hip flexion torque.
AB  - This study aimed to investigate muscle length-related electromyography (EMG) of
      the iliopsoas (IL) and other hip flexor muscles to determine individual muscle
      contributions to the hip flexion torque. Ten healthy sedentary young men
      participated in the EMG experiment. A subgroup of six subjects underwent a
      magnetic resonance imaging (MRI) measurement to confirm the region of the skin
      over the IL. Surface EMG signals were sampled from the IL, rectus femoris (RF),
      sartorius (SA), and tensor fasciae latae (TFL) using an active electrode. The
      subjects performed maximum voluntary isometric hip flexion with the right hip
      joint set at -10 degrees , 0 degrees , 30 degrees , and 60 degrees . The root
      mean square (RMS) value for the TFL at 30 degrees  (0.81 +/- 0.19, p <0.005) and
      60 degrees  (0.66 +/- 0.17, p <0.001) and the SA at 60 degrees  (0.62 +/- 0.24, p
      <0.005) were significantly decreased compared with those at 0 degrees . However,
      the RMS value for the IL and RF did not change significantly. The RMS value and
      muscle length changes were significantly correlated in the IL (r =0.39, p <0.05),
      SA (r =0.51, p <0.001), and TFL (r =0.70, p <0.001), but not in the RF (r =0.22,
      p =0.180). We conclude that, in a hip joint flexed position, the contribution of
      the IL to hip flexion movement is relatively larger than that of the other hip
      flexor muscles. 

PMID- 25392795
TI  - Contribution of dynamic sentinel lymphoscintigraphy images to the diagnosis of
      patients with malignant skin neoplasms in the upper and lower extremities.
AB  - The aim of the present study was to confirm the contribution of dynamic images in
      sentinel lymphoscintigraphy in malignant skin neoplasms: precisely, to
      investigate if dynamic images were necessary and to observe if dynamic images
      could reduce the areas needed for biopsy and dissection. Twenty-five patients
      with malignant skin neoplasms of the lower (n = 21) and upper (n = 4) extremities
      were retrospectively investigated. Images were evaluated by two independent
      reviewers, an expert in diagnostic radiology and nuclear medicine and a
      diagnostic radiologist in training. Visualized hot spots were assessed to be
      sentinel nodes using only static planar images. Next, both static planar and
      dynamic images were assessed. Reviewers scored diagnostic confidence values of
      determined sentinel nodes as follows: 0, cannot be decided; 1, possible; 2,
      probable; and 3, definitive. Patterns of lymphatic drainage were categorized into
      six different pathways: (1) inguinal type, (2) popliteal type, (3) inguinal and
      popliteal type, (4) axillary type, (5) cubital type, and (6) axillary and cubital
      type. In cases in the lower extremities, with dynamic images, the expert reviewer
      changed assessment in three cases and the trainee reviewer changed it in one
      case. There were no cases in which a decision was changed to be the same between
      both reviewers. Although the average diagnostic confidence value of assessment is
      usually higher with dynamic images, significant differences were not present. In
      cases of the upper extremities, both reviewers changed their assessment in one
      patient. By mutual agreement, cases in which assessment was changed with dynamic
      images were the inguinal and popliteal type, and the axillary and cubital type.
      The expert reviewer noticed lymphatic channels only visualized on dynamic images
      and changed assessment. Determination of whether or not a lymph node is a
      sentinel node depends on visualization of the lymphatic network. In the present
      circumstances, all biopsies of hot spots determined to be lymph nodes should not
      be excluded. However, excessive biopsies should be avoided as much as possible.
      It is necessary to use dynamic images alongside skillful observation. 

PMID- 25392796
TI  - Temporal trend, clinicopathologic and sociodemographic characterization of age at
      diagnosis of breast cancer among US women diagnosed from 1990 to 2009.
AB  - ABSTRACT: This paper investigates the distribution of age at diagnosis of female
      breast cancer and its association with temporal trend, clinicopathologic and
      sociodemographic variables in the presence of two latent clusters that are
      directly unobservable. Such clusters help to identify two subpopulations of
      either young or old patients whose etiologies are thought to be different. A
      large sample drawn from registry data from the National Cancer Institute's
      Surveillance, Epidemiology, and End Results program from 1990 to 2009 was
      analyzed using a two-component Gaussian mixture model. Evidence of a steady delay
      of age at diagnosis and an increasing proportion of young patients being
      diagnosed during the 20-year period was found. Histopathologic effects indicate
      that duct and lobular carcinomas differ significantly in regard to subpopulation
      membership, which confirms that they represent different etiologies. While the
      presence of estrogen receptor status in the model overlaps the effects of other
      important variables it is highly correlated with, it is found that the grade,
      extension and size of the tumor along with lymph node involvement status, race
      and marital status are important predictors of age at diagnosis. The results
      highlight the significant impacts that such features can have on breast cancer
      control efforts, and point to the importance of ensuring that medical decision
      making should use them along with an indicator of the age subpopulation a patient
      may belong to.

PMID- 25392797
TI  - Isolation and molecular identification of the etiological agents of
      streptococcosis in Nile tilapia (Oreochromis niloticus) cultured in net cages in
      Lake Sentani, Papua, Indonesia.
AB  - Infections with Streptococcus spp. were observed in Nile tilapia cultured in net
      cages in Lake Sentani, Papua, Indonesia. Clinical signs included exophthalmia,
      erratic swimming, ascites in abdominal cavity, and external hemorrhages. Four
      types of bacterial colonies (SK, K10, P20, and M12) were isolated from the brain,
      kidney, and eyes. Based on phenotypic and genetic (16S rDNA sequencing)
      characteristics, the isolates were identified as Streptococcus iniae (SK),
      Streptococcus agalactiae (K10 and P20) and Lactococcus garvieae (M12). The latter
      species has not been previously isolated or reported from fish streptococcosis in
      Indonesia. Intraperitoneal injection of healthy tilapia with the bacterial
      species caused significant morbidity (70%) within 3 days and 100% mortality at 6
      days post injection. Experimental infections and reisolation of the bacteria from
      morbid and dead fish suggest they are the causative agents of streptococcosis,
      which rendered high mortality among cage cultured Nile tilapia in Lake Sentani.
      Our results suggest the need for developing diagnostic tools for accurate
      identification of the agents of streptococcosis. As tilapia aquaculture continues
      to expand as a means of food production and livelihood in Indonesia, it becomes
      crucial to ensure that fish resources are monitored and protected from the
      adverse effects of infectious diseases. 

PMID- 25392798
TI  - Docking study of novel antihyperlipidemic thieno[2,3-d]pyrimidine; LM-1554, with
      some molecular targets related to hyperlipidemia - an investigation into its
      mechanism of action.
AB  - An investigation into the mechanism of antihyperlipidemic action of 2
      chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-one (LM-1554)
      was carried out through docking experiments with six different molecular targets;
      Niemann Pick C1 Like1 protein (NPC1L1), ATP citrate lyase (ACL), C-reactive
      protein (CRP), lanosterol 14alpha-demethylase (LDM), squalene synthase (SqS) and
      farnesiod X-receptor (FXR) known to be implicated in the physiology of
      hyperlipidemia. The interactions of LM-1554 were compared with the interactions
      of their respective co-crystallized native ligands at the active sites of these
      receptors. These comparisons are based on their docking parameters, as well as,
      types of interactions and vicinity with various amino acids in the active site
      pockets. The interaction of LM-1554 with the target, NPC1L1 has been found to be
      the quite favourable as compared to those with the other targets assessed in this
      study. 

PMID- 25392799
TI  - In vitro screening of antifungal activity of marine sponge extracts against five
      phytopathogenic fungi.
AB  - The aim of our research is the screening of extracts of marine sponges for their
      antifungal activity against phytopathogenic fungi. The in vitro screening of
      hydroalcoholic and organic extracts of ten marine sponges from Atlantic coast of
      Morocco against five phytopathogenic fungi (Fusarium oxysporum f.sp. melonis,
      Fusarium oxysporum f.sp. radicis-lycopersici, Fusarium oxysporum f.sp. ciceris,
      Botrytis cinerea and Penicillium digitatum) showed that only two sponges
      (Haliclona viscosa and Cynachirella tarentina) are active against all
      phytopathogenic fungi studied. 

PMID- 25392800
TI  - Molecular diagnosis of bird-mediated pest consumption in tropical farmland.
AB  - Biodiversity loss will likely have surprising and dramatic consequences for human
      wellbeing. Identifying species that benefit society represents a critical first
      step towards predicting the consequences of biodiversity loss. Though natural
      predators prevent billions of dollars in agricultural pest damage annually,
      characterizing which predators consume pests has proven challenging. Emerging
      molecular techniques may illuminate these interactions. In the countryside of
      Costa Rica, we identified avian predators of coffee's most damaging insect pest,
      the coffee berry borer beetle (Coleoptera:Scolytidae Hypothenemus hampeii), by
      assaying 1430 fecal samples of 108 bird species for borer DNA. While feeding
      trials confirmed the efficacy of our approach, detection rates were low.
      Nevertheless, we identified six species that consume the borer. These species had
      narrow diet breadths, thin bills, and short wings; traits shared with borer
      predators in other systems. Borer predators were not threatened; therefore,
      safeguarding pest control necessitates managing species beyond those at risk of
      regional extinction by maintaining populations in farmland habitats. Generally,
      our results demonstrate potential for pairing molecular methods with ecological
      analyses to yield novel insights into species interactions. 

PMID- 25392801
TI  - Bioremoval of the synthetic dye malachite green by marine Trichoderma sp.
AB  - In the present study, a marine strain of Trichoderma sp was used for degradation
      of a synthetic dye, malachite green. Individual and interaction effects of the
      physical and chemical factors that influenced the percentage of dye degradation
      were tested by response surface methodology. For optimization, enzyme production
      and dye degradation were assessed under different temperatures (5-40 degrees C),
      pH values (3-11), yeast extract (5-9 g L(-1)) and incubation period (0-15 days).
      The optimum conditions found for dye degradation, were 30 degrees C, pH 5.8, 5.81
      mg L(-1) yeast extract for an incubation period of 10 days. Whereas for laccase
      production they were 29 degrees C, pH 5.3, 7.7 mg L(-1) yeast extract for an
      incubation period of 12 days. It was confirmed that laccase production required
      the higher nitrogen source. Degradation of dye was confirmed by using analytical
      techniques such as FTIR, UV-vis spectral and scanning electron microscope
      analysis. Furthermore, toxicity effect of degraded and undegraded dye solutions
      was tested with Artemia salina. Hundred percent mortality was observed in
      undegraded dye solution as against only 2-5% in degraded dye solution. This work
      proved the potential of marine strain of Trichoderma Hypocrea lixii on dye
      degradation. 

PMID- 25392802
TI  - Differentiation-inducing and anti-proliferative activities of lupeol on canine
      melanoma cells.
AB  - Canine melanoma is the most common oral malignant tumor reported in the field of
      veterinary medicine. We found that lupeol, a lupine triterpene, inhibited mouse
      melanoma cell growth in vitro and in vivo by inducing cell differentiation. In
      the present study, we examined the differentiation-inducing activities of lupeol
      on 4 canine melanoma cells in vitro and in vivo. The induction of canine melanoma
      cell differentiation by lupeol was confirmed by evaluating some differentiation
      markers such as tyrosinase with real-time RT-PCR. Furthermore, we transplanted
      canine melanoma cells into a severe combined immunodeficiency mouse, and studied
      the anti-progressive effects of lupeol on tumor tissue. The gene expression of
      microphthalmia-associated transcription factor, tyrosinase, and tyrosinase
      related protein-2, which are markers of pigment cell differentiation, was induced
      in 4 canine oral malignant melanoma cells by lupeol, and the agent markedly
      inhibited tumor progression in canine melanoma-bearing mice. 

PMID- 25392803
TI  - The use of intravenous Milrinone to treat cerebral vasospasm following traumatic
      subarachnoid hemorrhage.
AB  - INTRODUCTION: Traumatic subarachnoid hemorrhage (SAH) is a common intracranial
      lesion after traumatic brain injury (TBI). As in aneurysmal SAH, cerebral
      vasospasm is a common cause of secondary brain injury and is associated with the
      thickness of traumatic SAH. Unfortunately, there is limited literature on an
      effective treatment of this entity. The vasodilatory and inotropic agent,
      Milrinone, has been shown to be effective in treating vasospasm following
      aneurysmal SAH. The authors hypothesized that this agent could be useful and safe
      in treating vasospasm following tSAH. CASE DESCRIPTIONS: Case reports of 2 TBI
      cases from a level 1 trauma centre with tSAH and whom developed delayed ischemic
      neurological deficits (DINDs) are presented. Intravenous Milrinone treatment was
      provided to each patient following the "Montreal Neurological Hospital Protocol".
      DISCUSSION AND EVALUATION: Both patients had an improvement in their DINDs
      following the treatment protocol. There were no complications of treatment and
      the Glasgow Outcome Scores of the patients ranged from 4 to 5. CONCLUSION: This
      is the first report of the use of intravenous Milrinone to treat cerebral
      vasospasm following traumatic SAH. This treatment option appeared to be safe and
      potentially useful at treating post-traumatic vasospasm. Prospective studies are
      necessary to establish Milrinone's clinical effectiveness in treating this type
      of cerebral vasospasm.

PMID- 25392804
TI  - Plasma heat shock protein 27 is associated with coronary artery disease,
      abdominal aortic aneurysm and peripheral artery disease.
AB  - Low protein levels of Hsp27 have been reported in atherosclerotic plaques. In
      addition, human studies have indicated that circulating Hsp27 levels are lower in
      coronary artery disease patients compared with controls. It remains, however,
      unclear whether this applies to other forms of atherosclerotic disease. Plasma
      Hsp27 from 280 subjects was examined by ELISA. The cohort included 80 coronary
      artery disease (CAD), 40 peripheral artery disease (PAD) and 80 abdominal aortic
      aneurysm (AAA) patients. Eighty elderly subjects, without any clinical history of
      vascular diseases, were used as a control group. Receiver operating curve (ROC)
      and logistic regression model analysis were performed to evaluate the potential
      value of Hsp27 as a circulating biomarker. Patients with atherosclerotic vascular
      diseases had significantly lower levels of Hsp27 than control subjects (p <
      0.001). Moreover, Hsp27 was significantly lower in CAD patients than other
      atherosclerotic vascular disease groups (p < 0.001). There was no difference in
      Hsp27 levels between the AAA and PAD groups. Using the ROC-generated optimal cut
      off values for Hsp27, logistic regression modeling indicated that low plasma
      Hsp27 was independently associated with the presence of multiple forms of
      atherosclerotic disease. In conclusion, circulating Hsp27 is significantly lower
      in patients with multiple forms of atherosclerotic arterial disease. 

PMID- 25392805
TI  - Significance of debriefing methods in simulation-based sedation training courses
      for medical safety improvement in Japan.
AB  - Based on the American Society of Anesthesiologists' Practice Guidelines for
      Sedation and Analgesia by Non-Anesthesiologists (ASA-SED), a sedation training
      course aimed at improving medical safety was developed by the Japanese
      Association for Medical Simulation in 2011. This study evaluated the effect of
      debriefing on participants' perceptions of the essential points of the ASA-SED. A
      total of 38 novice doctors participated in the sedation training course during
      the research period. Of these doctors, 18 participated in the debriefing group,
      and 20 participated in non-debriefing group. Scoring of participants' guideline
      perceptions was conducted using an evaluation sheet (nine items, 16 points)
      created based on the ASA-SED. The debriefing group showed a greater perception of
      the ASA-SED, as reflected in the significantly higher scores on the evaluation
      sheet (median, 16 points) than the control group (median, 13 points; p < 0.05).
      No significant differences were identified before or during sedation, but the
      difference after sedation was significant (p < 0.05). Debriefing after sedation
      training courses may contribute to better perception of the ASA-SED, and may lead
      to enhanced attitudes toward medical safety during sedation and analgesia. 

PMID- 25392806
TI  - Efficacy of long-term maintenance therapy with mycophenolate mofetil in lupus
      nephritis.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) has long been used to manage lupus
      nephritis. Despite research on its long-term efficacy, it is still warranted to
      conduct further investigation regarding its indications, safety and outcome. This
      study was intended to evaluate our proposed protocol in maintenance therapy with
      MMF. Twenty-four lupus nephritis patients were registered prior to their
      receiving 3-6 month induction therapy with monthly iv pulses of cyclophosphamide
      (CYC), followed by 24 month maintenance therapy using MMF and steroid. We defined
      end points as achievement of complete and partial remission, relapse, refractory
      to therapy as well as end stage renal disease (ESRD) and death. Friedman and
      repeated measurement tests were used to assess the effect of treatment on
      parameters over time. Complete renal remission was achieved in 79.16% until the
      end of the last follow up with an average period of 12.45 +/- 7.37 months since
      treatment commenced. Significant statistical differences were seen regarding
      proteinuria, hematuria, leukocyturia, plasma creatinine, C3, C4 before and after
      therapy (P < 0.05): plasma creatinine and proteinurea falling from 0.96 +/- 0.65
      to 0.75 +/- 0.19 mg/dl (P < 0.14) and from 1.64 +/- 1.12 to 0.27 +/- 0.60 gr/24 h
      (P < 0.001). By the end of 24-month, 95.8% of patients had been in remission.
      Four episodes of relapse ended in remission followed by retreatment. No life
      threatening side effects were observed in 66.6% of patients with fourteen cases
      of infection (58.3%). None of them developed ESRD. Maintenance therapy with MMF
      was shown to yield favorable outcome with minimal complications, in treating
      lupus nephritis (IRCT2012071710313N1).

PMID- 25392807
TI  - The use of FOCUS Harmonic scalpel compared to conventional haemostasis (knot and
      tie ligation) for thyroid surgery: a prospective randomized study.
AB  - Haemostasis is crucial in thyroid surgery to avoid intraoperative and
      postoperative complications. In the present study, we evaluated the efficiency
      and the safety of Harmonic scalpel when compared to conventional suture ligation
      in open total thyroidectomy. We enrolled 265 patients who underwent total
      thyroidectomy for multinodular disease since October 2011 up to October 2013.
      They were randomized into two groups: 141 in group HS (Harmonic Scalpel), 124 in
      group CT (Conventional tecnique). We recorded the following data: operative time,
      post-operative blood loss, length of hospital stay and complications. The
      patients were monitored for 48 hours after surgery. Several differences were
      observed between the two groups (HS vs CT): the use of Harmonic scalpel was
      associated to a significant reduction of surgical operative time (110 min in CT
      vs 79.36 min in HS, p = 0.00001) and also associated to a lower blood loss (97.38
      ml in CT vs 68.72 ml in HS, p = 0.00001). The length of stay was significantly
      shorter in the HS group (2.75 days in CT vs 1.93 days in HS) Complication rate
      was similar in the two groups. According to our experience, the Harmonic scalpel
      represents a safe alternative to conventional haemostasis in thyroid surgery,
      allowing for a significant reduction of operative time, blood loss and
      hospitalization. The rate of complication demonstrated no significant difference
      among the two groups. 

PMID- 25392808
TI  - An unusual high bifurcation and variable branching of the axillary artery in a
      Greek male cadaver.
AB  - INTRODUCTION: The axillary artery presents abnormalities in its origin and course
      and a variable branching. CASE DESCRIPTION: A rare case of axillary artery
      bifurcation and branching was observed in a 60-years-old European male cadaver of
      Greek origin. The right axillary artery at the second part was bifurcated into a
      superficial and a deep brachial artery. The superficial brachial artery
      anteromedial to the median nerve and lateral to the ulnar nerve gave off the
      acromio-thoracic artery and two lateral thoracic arteries. The deep brachial
      artery behind the median nerve, after giving rise to the anterior circumflex
      humeral artery trifurcated into a branch that coursed distally, the posterior
      circumflex humeral artery and the subscapular artery. The latter subdivided into
      the circumflex scapular artery, a muscular branch for the subscapularis and the
      thoracodorsal artery. The continuation of the deep brachial artery divided
      laterally into a humeral nutrient artery and medially into a trunk which
      trifurcated into the profunda brachii artery, a deep muscular branch and a branch
      to the posterior compartment of the arm. The profunda brachii artery ended as
      radial and middle collateral arteries. DISCUSSION AND EVALUATION: Deviations from
      the normal arterial pattern are of immense significance for anatomists, plastic,
      cardiovascular and orthopedic surgeons, vascular radiologists and interventional
      cardiologists.

PMID- 25392809
TI  - Selection of high temperature and salinity tolerant Trichoderma isolates with
      antagonistic activity against Sclerotium rolfsii.
AB  - Trichoderma isolates were collected from varied agro-climatic zones of India and
      screened for high temperature and salinity tolerance. Among all the isolates
      tested, T. asperellum, TaDOR673 was highly tolerant to heat shock of 52 degrees C
      with a mean spore count (log c.f.u/ml) of 4.33. The isolate after recovery from
      heat shock possessed higher germination rate and biomass production compared to
      its wild counterpart, upon prolonged exposure to 37 degrees C. Under stress,
      TaDOR673 accumulated >15% of trehalose and >5% of mannose and raffinose compared
      to the wild type strain signifying their role in stress tolerance. T. asperellum,
      TaDOR693 and T. asperellum, TaDORS3 were identified as superior salt-tolerant
      isolates. Interestingly, TaDOR673 also possessed similar tolerance levels to
      increasing saline concentrations as indicated by its improved colony growth under
      stress conditions. T. asperellum, TaDOR673 and T. asperellum, TaDOR7316
      effectively controlled the collar rot disease in groundnut by 79.7% when screened
      in vitro and in vivo. Thus, the study identified a potential thermotolerant and
      saline tolerant strain of Trichoderma, TaDOR673 that could be used as potential
      bioagent in stressed soils. 

PMID- 25392810
TI  - Isolated panniculitis with vasculitis of the male breast suspicious for
      malignancy on CT and ultrasound: a case report and literature review.
AB  - INTRODUCTION: We report a case of a 54-year-old male patient with a hard, painful
      nodule within his right breast which was misdiagnosed preoperatively as breast
      cancer. CASE DESCRIPTION: Preoperative work-up included physical examination, non
      contrast chest computed tomography (CT), sonography, and sono-guided breast
      biopsy. Isolated breast panniculitis with vasculitis (BPWV), a rare disease, was
      diagnosed by histopathologic examination of tissue obtained from excisional
      biopsy. DISCUSSION AND EVALUATION: Subcutaneous panniculitis with or without
      vasculitis, a condition of nonsuppurative inflammatory process involving the
      subcutaneous fat layer of skin, is related to different causes. A palpable benign
      male breast lesion resembling a malignancy includes gynecomastia, panniculitis
      with or without vasculitis, fat necrosis, ruptured epidermal cyst,
      pseudoangiomatous stromal hyperplasia, subareolar abscess, intraductal papilloma,
      hematoma, and atypical fibroadenoma. To make an accurate preoperative diagnosis
      of a male breast mass, a physician has to carefully analyze various imaging
      findings. The cases of BPWV may present as an isolated breast lesion or as a
      component of a systemic disease. The diagnosis of the reported patient was
      compatible with an isolated BPWV because panniculitis and/or vasculitis were not
      present at other sites or organs at the time of diagnosis or during follow-up.
      CONCLUSIONS: Excisional biopsy and clinical data can provide the correct
      diagnosis and determined the appropriate treatment strategy of a male BPWV.

PMID- 25392812
TI  - Gamification and service marketing.
AB  - Our paper addresses the development of the gamification concept with business
      applications. We report on our survey of customers and managers seeking to
      participate in gamification on their websites. We examined both customer and
      manager perspectives and compare survey results in terms of service marketing and
      characteristics of consumers who engage with gamification platforms. Our data
      supported a design theory delineating four key characteristics in gamification
      platforms that attract consumers toward an enterprise's website. Those features
      attract individuals through (1) Progress Paths, (2) Feedback and Reward, (3)
      Social Connection, and (4) Attractiveness of the site. Results from the managers'
      survey reflected key characteristics that must exist for implementation of a
      gamification platform. The data revealed a particular demographic profile of a
      gamification individual drawn to a website. These findings may help company
      managers who wish to adopt a gamification platform in the future. 

PMID- 25392811
TI  - Epidemiology of hypertension and its relationship with type 2 diabetes and
      obesity in eastern Morocco.
AB  - The major objectives of this work are to estimate the hypertension (HT) frequency
      in the east of Morocco and to study the relationship between HT, type 2 diabetes
      and obesity. Our sample is composed of 1628 adults aged 40 years and older,
      recruited voluntarily by using the convenience sampling method through 26
      screening campaigns in urban and rural areas of the east of Morocco. We
      enumerated 516 hypertensive people (31.7%), without significant difference
      between women (32.5%) and men (30.2%). The known hypertensive people represent
      10.1% of the whole sample. The frequency of HT, increases with age and it is more
      marked in rural (39.9%) than in urban areas (29%) (p < 0.001). It is
      significantly very high in diabetic subjects (69.9%) than among the non-diabetic
      ones (27.4%) (p < 0.001). The odd ratio (OR) of the diabetics to HT is 6.16
      (IC95% [4.33-8.74]). Among the obese persons, HT is present at (40.8%) vs.
      (30.2%) among the subjects of normal weight (p < 0.05). The OR of the obese to HT
      is 1.6 (IC95% [1.26 - 2.04]). In conclusion, our results show a high frequency of
      HT in the east of Morocco; it affects nearly one third of the adult population
      aged 40 years and older. The relations between type 2 diabetes and obesity have
      also been identified and estimated. 

PMID- 25392813
TI  - Counselling versus Low-Intensity Cognitive Behavioural Therapy for persistent sub
      threshold and mild Depression (CLICD): study protocol for a pilot/feasibility
      randomised controlled trial.
AB  - BACKGROUND: Persistent sub-threshold depressive symptoms are important because
      almost all patients who experience symptoms for more than 2 years go on to
      develop major depressive episodes. The National Institute for Health and Care
      Excellence in the United Kingdom recommends research into the efficacy of person
      centred counselling and low-intensity cognitive behavioural therapy for
      persistent sub-threshold and mild depression. METHODS/DESIGN: A two-arm, parallel
      group, pilot randomised trial to test the key components of trial delivery. The
      participants will be 50 patients with the diagnosis of persistent sub-threshold
      depressive symptoms and mild depression, recruited at five general practices in
      Glasgow, Scotland. Eligible patients will be randomised to receive either Person
      Centred Counselling (PCC) or Low-Intensity Cognitive Behavioural Therapy (LI
      CBT). The primary outcome measures are recruitment, adherence and retention rates
      at six months from baseline. The secondary outcome measures are changes at 6
      months on GRID-HAMD-17; recovery from, or prevention of, depression according to
      DSM-IV diagnosis at 6 months; changes at 6 months on the PHQ-9, WSAS, EQ5D, and
      SF12v2 MH Enhanced. We will provide estimates, with adequate precision, to help
      design future studies, of the recruitment rate and the proportion followed-up at
      6 months; and identify potential moderators of outcome. DISCUSSION: Evidence of
      comparative effectiveness of commonly used psychological treatments such as
      person-centred counselling and low intensity cognitive behavioural therapy is
      lacking in patients with sub-threshold and mild depression. This study will
      provide the information needed to construct a trial comparing these two
      treatments. This would help to inform early intervention treatment strategies for
      these conditions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN Register
      ID: ISRCTN60972025.

PMID- 25392814
TI  - Role of histo-blood group antigens in primate enteric calicivirus infections.
AB  - Human noroviruses (NoV) are associated with large proportion of non-bacterial
      diarrhea outbreaks together with > 50% of food-associated diarrheas. The function
      of histo-blood group antigens (HBGAs) in pathogenesis of virus infection was
      implicated. Until recently however, due to lack of a robust animal and in vitro
      models of human NoV infection, only the partial knowledge concerning the virus
      pathogenesis (receptor, co-receptor and target cell) and absence of viable
      vaccine candidates were the frequently referenced attributes of this acute
      diarrheal illness. Recently, a novel group of enteric caliciviruses (CV) of
      rhesus macaque host origin was discovered and described. The new genus within the
      family Caliciviridae was identified: Rhesus Enteric CV, i.e., "Recovirus" (ReCV).
      ReCVs are genetically and biologically close relatives of human NoVs, exhibit
      similar genetic and biological features and are capable of being propagated in
      cell culture. ReCVs cause symptomatic disease (diarrhea and fever) in
      experimentally inoculated macaques. Formulation and evaluation of efficient NoV
      vaccine might take several years. As suggested by recent studies, inhibition of
      HBGAs or HBGA-based antivirals could meanwhile be exploited as vaccine
      alternatives. The purpose of this minireview is to provide the guidance in
      respect to newly available primate model of enteric CV infection and its
      similarities with human NoV in utilizing the HBGAs as potential virus co
      receptors to indirectly address the unresolved questions of NoV pathogenesis and
      immunity. 

PMID- 25392815
TI  - 'Cough officer' nurses in a general medical clinic successfully detect drug
      susceptible and -resistant tuberculosis.
AB  - SETTING: Intensive case finding (ICF) for tuberculosis (TB) is recommended by the
      World Health Organization among known human immunodeficiency virus (HIV)
      patients. However, ICF may also be appropriate in generalized patient
      populations. OBJECTIVE: To evaluate the yield of ICF in a general medical clinic
      in a high HIV prevalence setting. METHODS: A nurse designated as a 'cough
      officer' identified clinic attendees with cough of >2 weeks and collected sputum
      for evaluation at the hospital and provincial referral laboratories. We
      retrospectively evaluated the number and proportion of patients with
      microbiologically confirmed TB identified in 2007-2008. RESULTS: Among 56 207
      clinic attendees, 1442 (2.6%) TB suspects were identified and 122 (8.5%) were
      sputum Ziehl-Neelsen (ZN) positive. Of 389 available results, 72 (18.5%) were
      auramine-positive and 99 (25.4%) were culture-positive; multidrug-resistant and
      extensively drug-resistant TB were identified in 16 (16.2%). The number needed to
      screen was 11.8 patients to identify one ZN-positive case and 3.9 to identify one
      culture-positive case. CONCLUSIONS: A nurse-facilitated cough officer program
      successfully identified TB suspects and drug-susceptible and drug-resistant TB.
      Culture was more sensitive for TB screening and critical for identifying drug
      resistance. ICF is operationally feasible, and should be expanded to general
      medical clinics in high HIV and TB prevalence, resource-limited settings.

PMID- 25392816
TI  - Quantitative cardiovascular imaging.

PMID- 25392817
TI  - A comparative analysis of ECG-gated steady state free precession magnetic
      resonance imaging versus transthoracic echocardiography for evaluation of aortic
      root dimensions.
AB  - PURPOSE: Accurate and reproducible measurement of aortic root dimensions is
      essential to inform clinical decision making. Transthoracic echocardiography
      (TTE) is the first line test for assessment of the aortic root but has potential
      limitations due to its limited field of view and restricted acoustic windows.
      Cardiac magnetic resonance imaging (MRI) is considered the "gold standard"
      technique for assessment of cardiac morphology and recently MRI reference ranges
      for aortic root dimensions have been published. The purpose of this study was to
      retrospectively compare aortic root measurements obtained from TTE with those
      derived from cardiac MRI. MATERIALS AND METHODS: Sixty-eight patients (40 males,
      28 females) who had undergone both cardiac MRI and TTE imaging within a 4-month
      interval (mean 62 days) were included. Steady-state-free precession MRI cine
      imaging was performed with an acquisition plane perpendicular to the aortic root
      and through the true cross sectional aortic valve plane. A cusp-commissure
      dimension from inside wall to inside wall in end-diastole was recorded and
      compared with standardized TTE derived Valsalva sinus measurements. Pearson
      correlation coefficients and a paired t-test were used for statistical analysis.
      RESULTS: Mean aortic root dimension by TTE was 3.2+/-0.5 cm and MRI was 3.4+/-0.4
      cm with a Pearson correlation coefficient of >0.7. Mean difference between TTE
      and MRI was 0.2+/-0.3 (P<0.001) with MRI producing a consistently higher measure.
      In four patients with a dilated aortic root by MRI the TTE measurement was within
      the normal reference range. In patients with a dilated aortic root (n=19) the
      mean difference was 0.2+/-0.4 cm (P<0.05) with MRI consistently producing the
      larger measure. In patients with a non-dilated aortic root t (n=49) the mean
      difference was 0.2+/-0.3 cm (P<0.05) with MRI consistently producing the larger
      measure. CONCLUSIONS: There is a high level of correlation between TTE and MRI
      derived aortic root measurements at the Valsalva sinus level. MRI consistently
      measures the aortic root dimension higher than TTE which may under diagnose
      patients with a mildly dilated aortic root. Further investigation is required to
      properly integrate MRI into imaging assessment algorithms.

PMID- 25392818
TI  - CT-angiography protocol with low dose radiation and low volume contrast medium
      for non-cardiac chest pain.
AB  - AIM: To evaluate the diagnostic quality of a new multiple detector-row computed
      tomography angiography (MDCT-A) protocol using low dose radiation and low volume
      contrast medium techniques for evaluation of non-cardiac chest pain. METHODS:
      Forty-five consecutive patients with clinically suspected noncardiac chest pain
      and requiring contrast-enhanced chest computed tomography (CT) were examined. The
      patients were assigned to the protocol, with 80 kilovolt (peak) (kV[p]) and 150
      effective milliampere-second (eff mA-s). In our study group, 40 mL of low osmolar
      contrast material was administered at 3.0 mL/s. RESULTS: In the study group, four
      patients with pulmonary embolism, four with pleural effusion, two with ascending
      aortic aneurysm and eight patients with pneumonic consolidation were detected.
      The mean attenuation of the pulmonary truncus and ascendant aortic locations was
      considered 264+/-44 and 249+/-51 HU, respectively. The mean effective radiation
      dose was 0.83 mSv for MDCT-A. CONCLUSIONS: Pulmonary artery and the aorta
      scanning simultaneously was significantly reduced radiation exposure with the
      mentioned dose saving technique. Additionally, injection of low volume (40 cc)
      contrast material may reduce the risk of contrast induced nephropathy, therefore,
      facilitate the diagnostic approach. This technique can be applied to all cases
      and particularly patients at high risk of contrast induced nephropathy due to its
      similar diagnostic quality with a low dose and high levels of arteriovenous
      enhancement simultaneously.

PMID- 25392819
TI  - Real-time magnetic resonance imaging of cardiac function and flow-recent
      progress.
AB  - Cardiac structure, function and flow are most commonly studied by ultrasound, X
      ray and magnetic resonance imaging (MRI) techniques. However, cardiovascular MRI
      is hitherto limited to electrocardiogram (ECG)-synchronized acquisitions and
      therefore often results in compromised quality for patients with arrhythmias or
      inabilities to comply with requested protocols-especially with breath-holding.
      Recent advances in the development of novel real-time MRI techniques now offer
      dynamic imaging of the heart and major vessels with high spatial and temporal
      resolution, so that examinations may be performed without the need for ECG
      synchronization and during free breathing. This article provides an overview of
      technical achievements, physiological validations, preliminary patient studies
      and translational aspects for a future clinical scenario of cardiovascular MRI in
      real time. 

PMID- 25392820
TI  - Established and emerging cardiovascular magnetic resonance techniques for the
      assessment of stable coronary heart disease and acute coronary syndromes.
AB  - Coronary heart disease (CHD) is a leading cause of death and disability
      worldwide. International guidelines recommend cardiovascular magnetic resonance
      (CMR) as an investigative option in those presenting with chest pain to inform
      diagnosis, risk stratify and determine the need for revascularization. CMR offers
      a unique method to assess global and regional cardiac function, myocardial
      perfusion, myocardial viability, tissue characterisation and proximal coronary
      anatomy all within a single study. This results in high diagnostic accuracy for
      the detection of significant coronary stenoses and an established role in the
      management of both stable CHD and acute coronary syndromes (ACS). The growing
      evidence base for the prognostic value of CMR, emerging advances in acquisition
      techniques, improvements in hardware and the completion of current major multi
      centre clinical CMR trials will further raise its prominence in international
      guidelines and routine cardiological practice. This article will focus on the
      rapidly evolving role of the multi-parametric CMR examination in the assessment
      of patients with stable and unstable CHD. 

PMID- 25392821
TI  - Quantification of regional myocardial wall motion by cardiovascular magnetic
      resonance.
AB  - Cardiovascular magnetic resonance (CMR) is a versatile tool that also allows
      comprehensive and accurate measurement of both global and regional myocardial
      contraction. Quantification of regional wall motion parameters, such as strain,
      strain rate, twist and torsion, has been shown to be more sensitive to early
      stage functional alterations. Since the invention of CMR tagging by magnetization
      saturation in 1988, several CMR techniques have been developed to enable the
      measurement of regional myocardial wall motion, including myocardial tissue
      tagging, phase contrast mapping, displacement encoding with stimulated echoes
      (DENSE), and strain encoded (SENC) imaging. These techniques have been developed
      with their own advantages and limitations. In this review, two widely used and
      closely related CMR techniques, i.e., tissue tagging and DENSE, will be discussed
      from the perspective of pulse sequence development and image-processing
      techniques. The clinical and preclinical applications of tissue tagging and DENSE
      in assessing wall motion mechanics in both normal and diseased hearts, including
      coronary artery diseases, hypertrophic cardiomyopathy, aortic stenosis, and
      Duchenne muscular dystrophies, will be discussed. 

PMID- 25392822
TI  - An overview on development and application of an experimental platform for
      quantitative cardiac imaging research in rabbit models of myocardial infarction.
AB  - To exploit the advantages of using rabbits for cardiac imaging research and to
      tackle the technical obstacles, efforts have been made under the framework of a
      doctoral research program. In this overview article, by cross-referencing the
      current literature, we summarize how we have developed a preclinical cardiac
      research platform based on modified models of reperfused myocardial infarction
      (MI) in rabbits; how the in vivo manifestations of cardiac imaging could be
      closely matched with those ex vivo macro- and microscopic findings; how these
      imaging outcomes could be quantitatively analyzed, validated and demonstrated;
      and how we could apply this cardiac imaging platform to provide possible
      solutions to certain lingering diagnostic and therapeutic problems in
      experimental cardiology. In particular, tissue components in acute cardiac
      ischemia have been stratified and characterized, post-infarct lipomatous
      metaplasia (LM) as a common but hardly illuminated clinical pathology has been
      identified in rabbit models, and a necrosis avid tracer as well as an anti
      ischemic drug have been successfully assessed for their potential utilities in
      clinical cardiology. These outcomes may interest the researchers in the related
      fields and help strengthen translational research in cardiovascular diseases. 

PMID- 25392823
TI  - CT angiography in the diagnosis of cardiovascular disease: a transformation in
      cardiovascular CT practice.
AB  - Computed tomography (CT) angiography represents the most important technical
      development in CT imaging and it has challenged invasive angiography in the
      diagnostic evaluation of cardiovascular abnormalities. Over the last decades,
      technological evolution in CT imaging has enabled CT angiography to become a
      first-line imaging modality in the diagnosis of cardiovascular disease. This
      review provides an overview of the diagnostic applications of CT angiography
      (CTA) in cardiovascular disease, with a focus on selected clinical challenges in
      some common cardiovascular abnormalities, which include abdominal aortic aneurysm
      (AAA), aortic dissection, pulmonary embolism (PE) and coronary artery disease. An
      evidence-based review is conducted to demonstrate how CT angiography has changed
      our approach in the diagnosis and management of cardiovascular disease. Radiation
      dose reduction strategies are also discussed to show how CT angiography can be
      performed in a low-dose protocol in the current clinical practice. 

PMID- 25392824
TI  - The role of magnetic resonance imaging in hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common inheritable cardiac
      disorder, with an estimated prevalence of 1:500 in the general population. Most
      cases of HCM are phenotypically expressed in adolescence or early adulthood but
      age-related penetrance with certain phenotypes is increasingly recognized.
      Clinical manifestations of HCM are usually the result of systolic and/or
      diastolic dysfunction, left ventricular outflow tract (LVOT) obstruction,
      arrhythmias and sudden cardiac death (SCD). In recent years magnetic resonance
      imaging (MRI) has become established as an important tool for the evaluation of
      suspected HCM as it can reliably establish the diagnosis, help distinguish HCM
      from other causes of left ventricular hypertrophy (LVH) and identify those
      patients at greatest risk of SCD. This article reviews the current status of MRI
      in the evaluation of the HCM patient including imaging protocols, disease
      characterization and the emerging role of MRI for risk stratification and proband
      screening. 

PMID- 25392825
TI  - Cardiovascular magnetic resonance T2* for tissue iron assessment in the heart.
AB  - Until recently, even in Europe and the US, iron induced cardiomyopathy was the
      most common cause of death for patients with thalassemia major (TM). In order to
      prevent deaths from this potentially reversible condition, accurate measurement
      of myocardial iron is needed to detect iron early and guide chelation therapy.
      Cardiovascular magnetic resonance (CMR) T2* is the method of choice for the
      assessment of cardiac iron and in the UK, where it was first introduced
      clinically, 60% reductions in overall mortality for TM have been observed. The
      history of T2* development is described in this article. T2* image acquisition
      and post processing techniques are reviewed. Remaining challenges and emerging
      techniques to potentially improve characterization of tissue iron are also
      discussed. 

PMID- 25392826
TI  - Focus on China: should clinicians engage in research? and lessons from other
      countries.
AB  - Following tremendous economic progress, society in China is also undergoing
      fundamental changes, as is the healthcare system. Currently the training of
      Chinese young doctors and their future work placement are all undergoing re
      structuring. We compiled some thoughts and opinions on the topic of 'should
      clinicians in China engage in research?', and publish them as a special report in
      this issue of Quantitative Imaging in Medicine and Surgery (QIMS). The
      contributors included some editorial members of this journal, and a few personal
      friends. Besides a few minor linguistic corrections, opinions from the
      contributors have not been edited, as we want authors' to write their own
      independent views. However, it is possible there is a selection bias of the
      contributors of this paper; more likely those who are interested in the medical
      research are selected and therefore the views of the contributors may not be
      generalizable. To compare the structure and funding of China with other
      countries, authors from UK, The Netherlands, France, and USA are also invited. 

PMID- 25392828
TI  - Comment on: Zhang Z, et al. Focus on China: should clinicians engage in research?
      and lessons from other countries. Quant Imaging Med Surg 2014;4:413-25.

PMID- 25392827
TI  - Big data and clinical research: focusing on the area of critical care medicine in
      mainland China.
AB  - Big data has long been found its way into clinical practice since the advent of
      information technology era. Medical records and follow-up data can be more
      efficiently stored and extracted with information technology. Immediately after
      admission a patient immediately produces a large amount of data including
      laboratory findings, medications, fluid balance, progressing notes and imaging
      findings. Clinicians and clinical investigators should make every effort to make
      full use of the big data that is being continuously generated by electronic
      medical record (EMR) system and other healthcare databases. At this stage, more
      training courses on data management and statistical analysis are required before
      clinicians and clinical investigators can handle big data and translate them into
      advances in medical science. China is a large country with a population of 1.3
      billion and can contribute greatly to clinical researches by providing reliable
      and high-quality big data. 

PMID- 25392829
TI  - Multidetector CT assessment of partial anomalous pulmonary venous return in
      association with sinus venosus type atrial septal defect.
AB  - Sinus venosus defects account for 15% of all atrial septal defects. They are
      frequently associated with partial anomalous pulmonary venous drainage of the
      right superior pulmonary vein into the superior vena cava (SVC). These defects
      require surgical correction and accurate pre-operative imaging assessment is
      critical. We present a case of sinus venosus atrial septal defect in which
      multidetector computed tomography (MDCT) angiography identified separate sites of
      pulmonary venous return. 

PMID- 25392830
TI  - Multidetector CT angiography characterisation of Type 4 dual left anterior
      descending coronary artery.
AB  - Duplication of the left anterior descending (LAD) coronary artery is a rare
      anomaly (incidence 1%) characterized by a short LAD that terminates high in the
      anterior interventricular groove and a long LAD that has a proximal course
      outside the anterior interventricular groove and returns to the groove in its
      distal course. The Type 4 variant of this anomaly is extremely rare whereby a
      long LAD arises from the right coronary sinus with a short LAD arising from the
      left mainstem. We present a case of Type 4 dual LAD which was characterised with
      multi-detector computed tomography (CT). 

PMID- 25392831
TI  - A morbid coexistence: thrombosed descending thoracic aorta aneurysm and aortic
      insufficiency with aortic diastolic reverse flow.
AB  - A 76-year-old woman presented with difficulty in speech and weakness on right arm
      and leg. Her medical history was remarkable only for uncontrolled hypertension
      for a long period. Dysarthria, right central facial paralysis, right hemiparesis
      and hypoactive deep tendon reflexes were noticed on neurological examination.
      Moderate degree aortic insufficiency with aortic diastolic reverse flow was
      detected on transthoracic echocardiography. Thrombosed aortic aneurysm on
      descending thoracic aorta, and an acute hemorrhagic infarction in the
      distribution of the left middle cerebral artery were depicted on thorax, and
      brain computed tomography scans, respectively. Cerebrovascular event was
      medically managed and whereas conservative management was offered for thrombosed
      descending thoracic aorta aneurysm. 

PMID- 25392832
TI  - Maturation of HBP surgery: worldwide advances to address worldwide problems.

PMID- 25392833
TI  - Gallbladder cancer.
AB  - Gallbladder cancer is the fifth most common cancer involving gastrointestinal
      tract, but it is the most common malignancy of the biliary tract, accounting for
      80-95% of biliary tract cancers. This tumor is a highly lethal disease with an
      overall 5-year survival of less than 5% and mean survival mere than 6 months. An
      early diagnosis is essential as this malignancy progresses silently with a late
      diagnosis. The percentage of patients diagnosed to have gallbladder cancer after
      simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%.
      Patients with preoperative suspicion of gallbladder cancer should not be treated
      by laparoscopy. Epidemiological studies have identified striking geographic and
      ethnic disparities-inordinately high occurrence in American Indians, elevated in
      Southeast Asia, yet quite low elsewhere in the Americas and the world.
      Environmental triggers play a critical role in eliciting cancer developing in the
      gallbladder, best exemplified by cholelithiasis and chronic inflammation from
      biliary tract and parasitic infections. Improved imaging modalities and improved
      radical aggressive surgical approach in the last decade has improved outcomes and
      helped prolong survival in patients with gallbladder cancer. The overall 5-year
      survival for patients with gallbladder cancer who underwent R0 curative resection
      was from 21% to 69%. In the future, the development of potential diagnostic
      markers for disease will yield screening opportunities for those at risk either
      with ethnic susceptibility or known anatomic anomalies of the biliary tract. 

PMID- 25392834
TI  - Pre-resectional inflow vascular control: extrafascial dissection of Glissonean
      pedicle in liver resections.
AB  - BACKGROUND/AIMS: We are evaluated technique of anatomic major and minor hepatic
      resections using suprahilar-extrafascial dissection of Glissonean pedicle with
      vascular stapling device for transection of hepatic vessels intending to minimize
      operative time, and blood loss. METHODOLOGY: We prospectively analyzed the
      clinical records of 170 patients who underwent hepatic resection by suprahilar
      extrafascial pedicle isolation and stapling technique in our clinic for emergency
      surgery in Belgrade. Patients who underwent hilar extrahepatic intrafascial
      dissection were excluded from the study. RESULTS: We performed 102 minor liver
      resections and 68 major hepatectomies. The minor liver resections were associated
      with significantly shorter surgery duration (95.1+/-31.1 vs. 186.6+/-56.5) and
      transection time (35.9+/-14.5 vs. 65.3+/-17.2) than major hepatectomies (P<0.001
      for all). The mean blood loss was 255.6+/-129.9 mL in minor resection and 385.7+/
      200.1 mL in major resection (P=0.003). The mean blood transfusion requirement was
      300.8+/-99.5 mL for the patients with minor hepatectomy and 450.9+/-89.6 mL for
      those with major liver resection (P=0.067). There was no significant difference
      in morbidity and mortality between the groups (P=0.989; P=0.920). Major as well
      as minor liver resection were a superior oncologic operation with no significant
      difference in the 3-year overall survival rates. CONCLUSIONS: Extrafascial
      dissection of Glissonean pedicle with vascular stapling represents both an
      effective and safe surgical technique of anatomical liver resection. Presented
      approach allows early and easy ischemic delineation of appropriate anatomical
      liver territory to be removed (hemiliver, section, segment) with selective inflow
      vascular control. Also, it is not time consuming and it is very useful in re
      resection, as well as oncologically reasonable.

PMID- 25392835
TI  - Post-hepatectomy liver failure.
AB  - Hepatectomies are among some of the most complex operative interventions
      performed. Mortality rates after major hepatectomy are as high as 30%, with post
      hepatic liver failure (PHLF) representing the major source of morbidity and
      mortality. We present a review of PHLF, including the current definition,
      predictive factors, pre-operative risk assessment, techniques to prevent PHLF,
      identification and management. Despite great improvements in morbidity and
      mortality, liver surgery continues to demand excellent clinical judgement in
      selecting patients for surgery. Appropriate choice of pre-operative techniques to
      improve the functional liver remnant (FLR), fastidious surgical technique, and
      excellent post-operative management are essential to optimize patient outcomes. 

PMID- 25392837
TI  - Potential use of Doppler perfusion index in detection of occult liver metastases
      from colorectal cancer.
AB  - Many clinical and preclinical studies demonstrated that measurements of liver
      hemodynamic [Doppler perfusion index (DPI)] may be used to accurately diagnose
      and predict liver metastases from primary colorectal cancer in a research
      setting. However, Doppler measurements have some serious limitations when applied
      to general population. Ultrasound is very operator-dependent, and requires
      skilled examiners. Also, many conditions may limit the use of Doppler ultrasound
      and ultrasound in general, such as the presence of air in digestive tract,
      cardiac arrhythmias, vascular anomalies, obesity and other conditions. Therefore,
      in spite of the results from clinical studies, its value may be limited in
      everyday practice. On the contrary, scientific research of the DPI in detection
      of liver metastases is of great importance, since current research speaks
      strongly for the presence of systemic vasoactive substance responsible for
      observed hemodynamic changes. Identification of such a systemic vasoactive
      substance may lead to the development of a simple and reproducible laboratory
      test that may reliably identify the presence of occult liver metastases and
      therefore increase the success of adjuvant chemotherapy through better selection
      of patients. Further research in this subject is therefore of great importance. 

PMID- 25392836
TI  - Pancreatic surgery: evolution and current tailored approach.
AB  - Surgical resection of pancreatic cancer offers the only chance for prolonged
      survival. Pancretic resections are technically challenging, and are accompanied
      by a substantial risk for postoperative complications, the most significant
      complication being a pancreatic fistula. Risk factors for development of
      pancreatic leakage are now well known, and several prophylactic pharmacological
      measures, as well as technical interventions have been suggested in prevention of
      pancreatic fistula. With better postoperative care and improved radiological
      interventions, most frequently complications can be managed conservatively. This
      review also attempts to address some of the controversies related to optimal
      management of the pancreatic remnant after pancreaticoduodenectomy. 

PMID- 25392838
TI  - Pancreatic fistula and postoperative pancreatitis after pancreatoduodenectomy for
      pancreatic cancer.
AB  - The most serious complication after pancreatoduodenectomy (PD) is pancreatic
      fistula (PF) type C, either as a consequence or independently from postoperative
      pancreatitis (PP). Differentiating between these two types of complications is
      often very difficult, if not impossible. The most significant factor in early
      diagnosis of PP after PD is an abrupt change in clinical status. In our
      retrospective study we also observed significantly higher levels of serum
      concentrations of CRP and AMS comparing to PF without PP. Based on our findings,
      CT scan is not beneficial in the early diagnosis of PP. Meantime PF type C is
      indication to operative revision with mostly drainage procedure which is
      obviously not much technically demanding, there are no definite guidelines on how
      to proceed in PP. Therefore the surgeon's experience determines not only whether
      PP will be diagnosed early enough and will be differentiated from PF without PP,
      but also whether a completion pancreatectomy will be performed in indicated
      cases. 

PMID- 25392839
TI  - Techniques for prevention of pancreatic leak after pancreatectomy.
AB  - Pancreatic resections are some of the most technically challenging operations
      performed by surgeons, and post-operative pancreatic fistula (POPF) are not
      uncommon, developing in approximately 13% of pancreaticoduodenectomies and 30% of
      distal pancreatectomies. Multiple trials of various operative techniques in the
      creation of the pancreatic ductal anastomosis have been conducted throughout the
      years, and herein we review the literature and outcomes data regarding these
      techniques, although no one technique of pancreatic ductal anastomosis has been
      shown to be superior in decreasing rate of POPF. Similarly, we review the
      literature regarding techniques of pancreatic closure after distal
      pancreatectomy. Again, no one technique has been shown to be superior in
      preventing POPF; however the use of buttressing material on the pancreatic staple
      line in the future may be a successful means of decreasing POPF. We review
      adjunctive techniques to decrease POPF such as pancreatic ductal stenting, the
      use of various topical biologic glues, and the use of somatostatin analogue
      medications. We conclude that future trials will need to be conducted to find
      optimal techniques to decrease POPF, and meticulous attention to intra-operative
      details and post-operative care by surgeons is necessary to prevent POPF and
      optimally care for patients undergoing pancreatic resection. 

PMID- 25392840
TI  - Robotic liver surgery.
AB  - Robotic surgery is an evolving technology that has been successfully applied to a
      number of surgical specialties, but its use in liver surgery has so far been
      limited. In this review article we discuss the challenges of minimally invasive
      liver surgery, the pros and cons of robotics, the evolution of medical robots,
      and the potentials in applying this technology to liver surgery. The current data
      in the literature are also presented. 

PMID- 25392841
TI  - "Vanishing liver metastases"-A real challenge for liver surgeons.
AB  - Expanded surgical intervention in colorectal liver metastasis (LM) and improved
      chemotherapy led to increasing problem of disappearing liver metastases (DLM).
      Treatment of those continues to evolve and poses a real challenge for HPB
      surgeons. This review discusses a clinical approach to DLM, emphasizing crucial
      steps in clinical algorithm. Particular issues such as imaging, intraoperative
      detection and surgical techniques are addressed. A step-by-step algorithm is
      suggested. 

PMID- 25392843
TI  - The laparoscopic liver resections-an initial experience and the literature
      review.
AB  - The laparoscopic liver resection (LLR) represents a new pathway in hepatic
      surgery. Several studies have reported its application in both malignant and
      benign liver diseases. The most common liver resections performed
      laparoscopically are wedge, segmental resections and metastasectomy; although in
      large centers the laparoscopic right and left hepatectomies have begun to perform
      more frequently. We report the initial experience in LLRs at our department
      including a case of the first laparoscopic left lateral liver bisegmentectomy
      performed in patient with follicular nodular hyperplasia and the 15 cases of
      wedge laparoscopic resections of echinococcic liver cysts. According to
      literature the mortality rate in LLRs is up to 0.3% and morbidity rate up to
      10.5%. The most common cause of the death is liver failure, while the most
      frequent complication is the bile leakage. Advantages for patients include
      smaller incisions, less blood loss, and shorter lengths of hospital stay. The
      LLRs in experienced hands were shown to be safe with acceptable morbidity and
      mortality for both minor and major hepatic resections in benign and malignant
      diseases. 

PMID- 25392842
TI  - Small for size liver remnant following resection: prevention and management.
AB  - In the latest decades an important change was registered in liver surgery,
      however the management of liver cirrhosis or small size hepatic remnant still
      remains a challenge. Currently post-hepatectomy liver failure (PLF) is the major
      cause of death after liver resection often associated with sepsis and ischemia
      reperfusion injury (IRI). ''Small-for-size'' syndrome (SFSS) and PFL have similar
      mechanism presenting reduction of liver mass and portal hyper flow beyond a
      certain threshold. Few methods are described to prevent both syndromes, in the
      preoperative, perioperative and postoperative stages. Additionally to portal vein
      embolization (PVE), radiological examinations (mainly CT and/or MRI), and more
      recently 3D computed tomography are fundamental to quantify the liver volume (LV)
      at a preoperative stage. During surgery, in order to limit parenchymal damage and
      optimize regenerative capacity, some hepatoprotective measures may be employed,
      among them: intermittent portal clamping and hypothermic liver preservation.
      Regarding the treatment, since PLF is a quite complex disease, it is required a
      multi-disciplinary approach, where it management must be undertaken in
      conjunction with critical care, hepatology, microbiology and radiology services.
      The size of the liver cannot be considered the main variable in the development
      of liver dysfunction after extended hepatectomies. Additional characteristics
      should be taken into account, such as: the future liver remnant; the portal blood
      flow and pressure and the exploration of the potential effects of regeneration
      preconditioning are all promising strategies that could help to expand the
      indications and increase the safety of liver surgery. 

PMID- 25392844
TI  - Complications after percutaneous ablation of liver tumors: a systematic review.
AB  - BACKGROUND: Although ablation therapy has been accepted as a promising and safe
      technique for treatment of unrespectable hepatic tumors, investigation of its
      complications has been limited. A physician who performs ablation treatment of
      hepatic malignancies should be aware of the broad spectrum of complications.
      Proper management is possible only if the physician Performing ablation
      understands the broad spectrum of complications encountered after ablation.
      OBJECTIVES: TO SYSTEMATICALLY REVIEW THE COMPLICATIONS AFTER DIFFERENT ABLATION
      MODALITIES: Radiofrequency ablation (RFA), microwave ablation (MWA) and Nano
      knife for the treatment of liver tumors and analyze possible risk factors that
      precipitate these complications. SEARCH METHODS: WE PERFORMED ELECTRONIC SEARCHES
      IN THE FOLLOWING DATABASES: MEDLINE, EMBASE and COCHARNE. Current trials were
      identified through the Internet (from January 1, 2000 to January 1, 2014). We
      included only studies who specific mentioned complications after liver ablation
      therapy (RFA/MWA/Nano knife). MAIN RESULTS: A total of 2,588 publications were
      identified, after detailed examination only 32 publications were included in the
      review. The included studies involved 15,744 participants. According to the type
      of technique, 13,044 and 2,700 patients were included for RFA and MWA. Analysis
      showed a pooled mortality of 0.15% for RFA, and 0.23% for MWA. CONCLUSIONS: This
      systematic review gathers information from controlled clinical trials and
      observational studies which are vulnerable to different types of bias, never the
      less RFA and MWA can be considered safe techniques for the treatment of liver
      tumors.

PMID- 25392845
TI  - The surgical treatment of patients with colorectal cancer and liver metastases in
      the setting of the "liver first" approach.
AB  - A surgical resection is the only curative method in the therapy of colorectal
      carcinoma and liver metastases. Along with the development of interventional
      radiological techniques the indications for surgery widen. The number of
      metastases and patients age should not present a contraindication for surgical
      resection. However, there are still some doubts concerns what to resect first in
      cases of synchronous colorectal carcinoma and liver metastases and how to ensure
      the proper remnant liver volume in order to avoid postoperative liver failure and
      achieve the best results. Through this review the surgical therapy of colorectal
      carcinoma and liver metastases was revised in the setting of "liver-first"
      approach and the problem of ensuring of remnant liver volume. 

PMID- 25392846
TI  - Extending Findings of a Relation between Posttraumatic Stress Disorder and
      Emotion Dysregulation among African American Individuals: A Preliminary
      Examination of the Moderating Role of Gender.
AB  - Although previous literature highlights the robust relationship between
      posttraumatic stress disorder (PTSD) and emotion dysregulation across diverse
      racial/ethnic populations, few studies have examined factors that may influence
      levels of emotion dysregulation among African American individuals with PTSD. The
      goal of the current study was to extend previous findings by examining the
      moderating role of gender in the relationship between PTSD and emotion
      dysregulation in an African American sample. Participants were 107 African
      American undergraduates enrolled in a historically black college in the southern
      United States who reported exposure to a Criterion A traumatic event.
      Participants with probable PTSD (vs. no PTSD) reported significantly greater
      emotion dysregulation, both overall and across many of the specific dimensions.
      Although the main effect of gender on emotion dysregulation was not statistically
      significant, results revealed a significant interaction between gender and
      probable PTSD status for overall emotion dysregulation and the specific
      dimensions of difficulties controlling impulsive behaviors when distressed,
      limited access to emotion regulation strategies perceived as effective, and lack
      of emotional clarity. Specifically, post-hoc analyses revealed a significant
      association between probable PTSD and heightened emotion dysregulation among
      African American women but not African American men, with African American women
      with probable PTSD reporting significantly higher levels of these dimensions of
      emotion dysregulation than all other groups. Findings highlight the relevance of
      emotion dysregulation to PTSD among African American women in particular,
      suggesting the importance of assessing and treating emotion dysregulation within
      this population.

PMID- 25392847
TI  - Urinary phthalate metabolite concentrations among men with inflammatory bowel
      disease on mesalamine therapy.
AB  - BACKGROUND: Phthalates, a family of compounds used in a variety of consumer
      products, are reproductive and developmental toxicants in experimental animals.
      One of these phthalates, dibutyl phthalate (DBP), is an inactive ingredient in
      the coating of Asacol. AIM: To determine if men with inflammatory bowel disease
      taking Asacol have higher urinary concentrations of monobutyl phthalate (MBP), a
      metabolite of DBP, compared to the general population in the United States.
      METHODS: Five patients at the Massachusetts General Hospital Crohn's and Colitis
      Center, taking at least 800 mg of Asacol three times a day, provided one spot
      urine sample. Urinary MBP and other phthalate metabolite concentrations were
      measured by using online solid phase extraction coupled with isotope dilution
      high-performance liquid chromatography tandem mass spectrometry. RESULTS: In four
      of the five men, the urinary concentrations of MBP (9888 ng/mL, 12,308 ng/mL,
      10,124 ng/mL, and 41,590 ng/mL) and of a minor DBP metabolite, mono(3
      carboxypropyl) phthalate (MCPP, 116.4 ng/mL, 163.4 ng/mL 72.6 ng/mL, 5604 ng/mL)
      were orders of magnitude higher than the background concentrations among the US
      general population. One subject missed his morning Asacol dose and had urinary
      MBP concentrations (17.5 ng/mL) similar to background levels. CONCLUSION: We
      confirmed that men with inflammatory bowel disease taking Asacol have urinary
      concentrations of MBP and MCPP much higher than background levels.

PMID- 25392848
TI  - Welcome to the Journal of Surgery and Science!

PMID- 25392849
TI  - The Impact of Obesity and Weight Loss on Urinary and Bowel Incontinence Symptoms
      in Women.

PMID- 25392850
TI  - Conditional anomaly detection methods for patient-management alert systems.
AB  - Anomaly detection methods can be very useful in identifying unusual or
      interesting patterns in data. A recently proposed conditional anomaly detection
      framework extends anomaly detection to the problem of identifying anomalous
      patterns on a subset of attributes in the data. The anomaly always depends (is
      conditioned) on the value of remaining attributes. The work presented in this
      paper focuses on instance-based methods for detecting conditional anomalies. The
      methods rely on the distance metric to identify examples in the dataset that are
      most critical for detecting the anomaly. We investigate various metrics and
      metric learning methods to optimize the performance of the instance-based anomaly
      detection methods. We show the benefits of the instance-based methods on two real
      world detection problems: detection of unusual admission decisions for patients
      with the community-acquired pneumonia and detection of unusual orders of an HPF4
      test that is used to confirm Heparin induced thrombocytopenia - a life
      threatening condition caused by the Heparin therapy.

PMID- 25392851
TI  - Locally Weighted Multi-atlas Construction.
AB  - In image-based medical research, atlases are widely used in many tasks, for
      example, spatial normalization and segmentation. If atlases are regarded as
      representative patterns for a population of images, then multiple atlases are
      required for a heterogeneous population. In conventional atlas construction
      methods, the "unit" of representative patterns is images. Every input image is
      associated with its most similar atlas. As the number of subjects increases, the
      heterogeneity increases accordingly, and a big number of atlases may be needed.
      In this paper, we explore using region-wise, instead of image-wise, patterns to
      represent a population. Different parts of an input image is fuzzily associated
      with different atlases according to voxel-level association weights. In this way,
      regional structure patterns from different atlases can be combined together.
      Based on this model, we design a variational framework for multi-atlas
      construction. In the application to two T1-weighted MRI data sets, the method
      shows promising performance, in comparison with a conventional unbiased atlas
      construction method.

PMID- 25392852
TI  - Thrombin generation and low-molecular-weight heparin prophylaxis in pregnant
      women with thrombophilia.
AB  - Pregnancy is associated with increased risk of venous thromboembolism, especially
      in the presence of thrombophilia. However, there is no consensus on the optimal
      approach for thromboprophylaxis in this population. Recent evidence suggests that
      thrombin generation correlates with the overall procoagulant state of the plasma.
      Our aim was to evaluate thrombin generation in a prospective cohort of
      thrombophilic pregnant women, and investigate the effectiveness of low-molecular
      weight heparin (LMWH) prophylaxis in pregnancy. Women with severe (n=8), mild
      (n=47) and no (n=15) thrombophilia were followed throughout their pregnancies.
      Thrombin generation was evaluated in each trimester as well as five days and
      eight weeks postpartum (as a reference category). In women undergoing LMWH
      prophylaxis, thrombin generation and anti-Factor-Xa activity were measured just
      before and 4 hours after administration (peak effect). Thrombin generation was
      determined using Technothrombin TGA assay system. For the analysis, median peak
      thrombin and endogenous thrombin potential were used. Peak thrombin and
      endogenous thrombin potential were increased during pregnancy compared to the non
      pregnant state with the highest results in the severe thrombophilia group. In
      women receiving LMWH prophylaxis a decrease was observed in thrombin generation
      at peak effect but over the progression of pregnancy the extent of this decrease
      reduced in a stepwise fashion. Our results show that thrombin generation
      demonstrates the hypercoagulable state in thrombophilic pregnancies. In addition,
      we found the effect of LMWH prophylaxis to progressively decrease with advancing
      stages of pregnancy. 

PMID- 25392853
TI  - Serum NOX2 and urinary isoprostanes predict vascular events in patients with
      atrial fibrillation.
AB  - There are limited prospective data evaluating the role of urinary F2-IsoP and
      NOX2 as predictive markers in atrial fibrillation (AF). The aim of this study was
      to analyse the role of urinary prostaglandin PGF2alpha (8-iso-PGF2alpha) and
      NOX2, markers of systemic oxidative stress, in predicting cardiovascular (CV)
      events and mortality in anticoagulated non-valvular AF patients. This was a
      prospective study including 1,002 anticoagulated AF patients, followed for a
      median time of 25.7 months (interquartile range: 14.8-50.9). All major CV events,
      CV deaths and all-cause deaths were considered as primary outcomes of the study.
      CV events included fatal/nonfatal ischaemic stroke, fatal/nonfatal myocardial
      infarction (MI), cardiac revascularisation and transient ischaemic attack (TIA).
      Oxidative stress biomarkers, such as urinary 8-iso-PGF2alpha and serum sNOX2-dp,
      a marker of NOX2 activation, were measured. A CV event occurred in 125 patients
      (12.5 %); 78 CV deaths and 31 non-CV deaths were registered. 8-iso-PGF2alpha and
      sNOX2-dp were correlated (Rs=0.765 p< 0.001). A significant increased cumulative
      incidence of CV events and CV deaths was observed across tertiles for 8-iso
      PGF2alpha and sNOX2-dp. An increased rate of all-cause death was observed across
      tertiles of urinary 8-iso-PGF2alpha. In Cox or Fine and Gray models, 8-iso
      PGF2alpha predicted CV events and CV and non-CV deaths. The addition of tertiles
      of 8-iso-PGF2alpha to CHA2DS2-VASc score improved ROC curves for each outcome and
      NRI for CV events (0.24 [0.06-0.53] p=0.0067). The study shows that in AF
      patients 8-iso-PGF2alpha and NOX2 levels are predictive of CV events and total
      mortality. F2-IsoP may complement conventional risk factors in prediction of CV
      events.

PMID- 25392854
TI  - Platelet CCL5 links acute coronary syndrome and vascular inflammation.

PMID- 25392855
TI  - A genetic algorithm based multi-objective shape optimization scheme for
      cementless femoral implant.
AB  - The shape and geometry of femoral implant influence implant-induced
      periprosthetic bone resorption and implant-bone interface stresses, which are
      potential causes of aseptic loosening in cementless total hip arthroplasty (THA).
      Development of a shape optimization scheme is necessary to achieve a trade-off
      between these two conflicting objectives. The objective of this study was to
      develop a novel multi-objective custom-based shape optimization scheme for
      cementless femoral implant by integrating finite element (FE) analysis and a
      multi-objective genetic algorithm (GA). The FE model of a proximal femur was
      based on a subject-specific CT-scan dataset. Eighteen parameters describing the
      nature of four key sections of the implant were identified as design variables.
      Two objective functions, one based on implant-bone interface failure criterion,
      and the other based on resorbed proximal bone mass fraction (BMF), were
      formulated. The results predicted by the two objective functions were found to be
      contradictory; a reduction in the proximal bone resorption was accompanied by a
      greater chance of interface failure. The resorbed proximal BMF was found to be
      between 23% and 27% for the trade-off geometries as compared to ~39% for a
      generic implant. Moreover, the overall chances of interface failure have been
      minimized for the optimal designs, compared to the generic implant. The adaptive
      bone remodeling was also found to be minimal for the optimally designed implants
      and, further with remodeling, the chances of interface debonding increased only
      marginally. 

PMID- 25392856
TI  - Effects of different loading patterns on the trabecular bone morphology of the
      proximal femur using adaptive bone remodeling.
AB  - In this study, the changes in the bone density of human femur model as a result
      of different loadings were investigated. The model initially consisted of a solid
      shell representing cortical bone encompassing a cubical network of interconnected
      rods representing trabecular bone. A computationally efficient program was
      developed that iteratively changed the structure of trabecular bone by keeping
      the local stress in the structure within a defined stress range. The stress was
      controlled by either enhancing existing beam elements or removing beams from the
      initial trabecular frame structure. Analyses were performed for two cases of
      homogenous isotropic and transversely isotropic beams.Trabecular bone structure
      was obtained for three load cases: walking, stair climbing and stumbling without
      falling. The results indicate that trabecular bone tissue material properties do
      not have a significant effect on the converged structure of trabecular bone. In
      addition, as the magnitude of the loads increase, the internal structure becomes
      denser in critical zones. Loading associated with the stumbling results in the
      highest density;whereas walking, considered as a routine daily activity, results
      in the least internal density in different regions. Furthermore, bone volume
      fraction at the critical regions of the converged structure is in good agreement
      with previously measured data obtained from combinations of dual X-ray
      absorptiometry (DXA) and computed tomography (CT). The results indicate that the
      converged bone architecture consisting of rods and plates are consistent with the
      natural bone morphology of the femur. The proposed model shows a promising means
      to understand the effects of different individual loading patterns on the bone
      density.

PMID- 25392857
TI  - Viral load versus CD4+ monitoring and 5-year outcomes of antiretroviral therapy
      in HIV-positive children in Southern Africa: a cohort-based modelling study.
AB  - OBJECTIVES: Many paediatric antiretroviral therapy (ART) programmes in Southern
      Africa rely on CD4+ to monitor ART. We assessed the benefit of replacing CD4+ by
      viral load monitoring. DESIGN: A mathematical modelling study. METHODS: A
      simulation model of HIV progression over 5 years in children on ART,
      parameterized by data from seven South African cohorts. We simulated treatment
      programmes with 6-monthly CD4+ or 6- or 12-monthly viral load monitoring. We
      compared mortality, second-line ART use, immunological failure and time spent on
      failing ART. In further analyses, we varied the rate of virological failure, and
      assumed that the rate is higher with CD4+ than with viral load monitoring.
      RESULTS: About 7% of children were predicted to die within 5 years, independent
      of the monitoring strategy. Compared with CD4+ monitoring, 12-monthly viral load
      monitoring reduced the 5-year risk of immunological failure from 1.6 to 1.0% and
      the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with
      CD4+ compared with 12% with viral load monitoring switched to second-line ART.
      Differences became larger when assuming higher rates of virological failure. When
      assuming higher virological failure rates with CD4+ than with viral load
      monitoring, up to 4.2% of children with CD4+ compared with 1.5% with viral load
      monitoring experienced immunological failure; the mean time spent on failing ART
      was 27.3 months with CD4+ monitoring and 6.0 months with viral load monitoring.
      Conclusion: Viral load monitoring did not affect 5-year mortality, but reduced
      time on failing ART, improved immunological response and increased switching to
      second-line ART.

PMID- 25392858
TI  - Is it time to revise antiretrovirals dosing? a pharmacokinetic viewpoint.
AB  - We document our experience with therapeutic drug monitoring (TDM) of
      antiretroviral agents (1807 determinations) carried out as day-by-day clinical
      practice for the optimization of drug dosing in HIV-infected patients. A
      significant proportion of patients had lopinavir, atazanavir and nevirapine
      trough concentrations exceeding the upper therapeutic threshold. Further studies
      are needed to identify good candidates/drugs for TDM, eventually allowing the
      selection of patients who may benefit from TDM-driven adjustments in
      antiretrovirals dosage.

PMID- 25392859
TI  - Comparison of central and local HIV-1 RNA quantification from two international
      clinical trials.
AB  - Local and centrally measured plasma HIV RNA (pVL) were assessed for agreement in
      two trials, ENCORE1 and SECOND-LINE. The proportion less than 200 copies/ml at
      week 48 was qualitatively similar [ENCORE1 2.5% (95% confidence interval, 95% CI 
      1.6 to 6.6); 1.9% (95% CI -1.9 to 2.1); SECOND-LINE 0.3% (95% CI -6.4 to 10.0);
      1.8% (95% CI -4.7 to 8.3)]. The mean difference in log10 pVL copies/ml at weeks 0
      and 48 was less than 0.2 log10 copies/ml in both trials. Our data indicate that
      central testing of pVL in HIV therapeutic trials is not warranted.

PMID- 25392861
TI  - Author response.

PMID- 25392862
TI  - Author response.

PMID- 25392863
TI  - Statistical analysis of shear wave speed in the uterine cervix.
AB  - Although cervical softening is critical in pregnancy, there currently is no
      objective method for assessing the softness of the cervix. Shear wave speed (SWS)
      estimation is a noninvasive tool used to measure tissue mechanical properties
      such as stiffness. The goal of this study was to determine the spatial
      variability and assess the ability of SWS to classify ripened versus unripened
      tissue samples. Ex vivo human hysterectomy samples (n = 22) were collected; a
      subset (n = 13) were ripened. SWS estimates were made at 4 to 5 locations along
      the length of the canal on both anterior and posterior halves. A linear mixed
      model was used for a robust multivariate analysis. Receiver operating
      characteristic (ROC) analysis and the area under the ROC curve (AUC) were
      calculated to describe the utility of SWS to classify ripened versus unripened
      tissue samples. Results showed that all variables used in the linear mixed model
      were significant ( p < 0.05). Estimates at the mid location for the unripened
      group were 3.45 +/- 0.95 m/s (anterior) and 3.56 +/- 0.92 m/s (posterior), and
      2.11 +/- 0.45 m/s (anterior) and 2.68 +/- 0.57 m/s (posterior) for the ripened (
      p < 0.001). The AUCs were 0.91 and 0.84 for anterior and posterior, respectively,
      suggesting that SWS estimates may be useful for quantifying cervical softening.

PMID- 25392864
TI  - There is plenty of room at the bottom.

PMID- 25392865
TI  - The development of ever more advanced technologies depends very critically on the
      definitions of materials with appropriate characteristics.

PMID- 25392866
TI  - The bathe-saltpeter equation.

PMID- 25392867
TI  - Organic biomass.

PMID- 25392869
TI  - The massive exploitation of fossil fuels.

PMID- 25392868
TI  - About recent developments of synthetic polymers for a suitable cell
      adhesion/growth support in tissue engineering-based either augmentation
      cystoplasty or neobladder.
AB  - Among the regenerative medicine technologies, the tissue engineering has emerged,
      in recent years, as a prominent tool, particularly given the tremendous
      developments in the field of synthetic polymer-based scaffolds. Scaffold surface
      coatings with either extracellular matrix (ECM) proteins or integrin-binding
      bioactive peptide sequences, such as RDG, proved to be extremely useful to
      enhance cell adhesion and growth. Nevertheless, about it, excellent effects may
      be reached by electrospinning-obtained nanofiber-structured synthetic polymer
      scaffold - such as polyurethane or polyethylene-terephthalate electrospun
      nanofibers - without resorting to surface- coated adhesion proteins. As for
      bladder tissue engineering, properly cell-seeded synthetic biomaterial-based
      scaffolds allow today timely chances to obtain constructs provided with specific
      bladder native tissue-like both histological-immunohistochemical and functional
      dynamic features. Recent bright advances in the tissue engineering research,
      particularly in the area of materials science - together with increasing
      availability of suitable bioreactors - and stem cell biology, make foreseeable,
      in the near future, further technological improvements that might widen the
      clinical applications of bladder tissue engineering up to whole bladder
      replacement in radical tumor surgery.

PMID- 25392870
TI  - Regarding "Impact of transthoracic endoscopic sympathectomy om plantar
      hyperhidrosis".

PMID- 25392871
TI  - Author reply: To PMID 24479620.

PMID- 25392872
TI  - [Not Available].

PMID- 25392873
TI  - [Not Available].

PMID- 25392874
TI  - [Antiretroviral treatment regimens: less tablets for a better result].

PMID- 25392875
TI  - [Not providing results of UT colonization].

PMID- 25392876
TI  - The author file: Paola Picotti.

PMID- 25392877
TI  - Points of significance: nested designs. For studies with hierarchical noise
      sources, use a nested analysis of variance approach.

PMID- 25392878
TI  - A systems view of cellular reprogramming.

PMID- 25392879
TI  - A windowless peek into the brain.

PMID- 25392880
TI  - Transcription factors without footprints.

PMID- 25392881
TI  - Imaging without labels.

PMID- 25392882
TI  - Painting a picture of protein interaction.

PMID- 25392883
TI  - Deep mutational scans with targeted editing.

PMID- 25392884
TI  - A stir in the cytoplasm.

PMID- 25392885
TI  - Response.

PMID- 25392886
TI  - Response.

PMID- 25392887
TI  - Sentinel node biopsy is now part of routine staging in patients with clinically
      localized melanoma.

PMID- 25392888
TI  - Response.

PMID- 25392905
TI  - Tunnel conduction in epitaxial bilayers of ferromagnetic LaCoO3/La2/3Sr1/3MnO3
      deposited by a chemical solution method.
AB  - We report magnetic and electronic transport measurements across epitaxial
      bilayers of ferromagnetic insulator LaCoO3 and half-metallic ferromagnet
      La2/3Sr1/3MnO3 (LCO/LSMO: 3.5 nm/20 nm) fabricated by a chemical solution method.
      The I-V curves at room temperature and 4K measured with conducting atomic force
      microscopy (CAFM) on well-defined patterned areas exhibit the typical features of
      a tunneling process. The curves have been fitted to the Simmons model to
      determine the height (phi) and width (s) of the insulating LCO barrier. The
      results yield phi = 0.40 +/- 0.05 eV (0.50 +/- 0.01 eV) at room temperature (4K)
      and s = 3 nm, in good agreement with the structural analysis. Our results
      demonstrate that this chemical method is able to produce epitaxial
      heterostructures with the quality required for this type of fundamental studies
      and applications. 

PMID- 25392906
TI  - Excision of fascia in melanoma thicker than 2 mm: no evidence for improved
      clinical outcome.
AB  - BACKGROUND: Lack of evidence-based data causes significant variation among
      surgeons concerning the depth of wide excision for primary cutaneous melanomas.
      OBJECTIVES: To evaluate the clinical effect of excision of the deep fascia in
      melanomas thicker than 2 mm on patient outcome. METHODS: We performed a
      retrospective cohort review (1996-2012) of patients with melanomas thicker than 2
      mm. Included patients underwent excision with a 1-cm margin. Data collected
      included the patients' sex, age, tumour location, tumour type, Breslow depth and
      presence of ulceration. Local recurrences, locoregional and distant metastases,
      and disease-free and overall survival were compared between the fascia-excised
      and the fascia-preserved groups. RESULTS: Out of 2182 patients with malignant
      melanomas, 213 melanomas thicker than 2 mm, with a median follow-up of 1547 days,
      were included. The mean age of the patients was 62.6 years and the mean Breslow
      depth was 4.2 mm. Analysis of data for death attributable to melanoma (P = 0.72),
      local recurrence (P = 0.71), and locoregional (P = 0.87) and distant metastases
      (P = 0.34) were not significantly different between the study groups.
      Furthermore, Kaplan-Meier and Cox regression analysis of both groups showed no
      evidence of significant difference regarding disease-free [P = 0.35; hazard ratio
      (HR) 1.25; 95% confidence interval (CI) 0.79-1.97] and overall survival (P =
      0.63; HR 1.18; 95% CI 0.61-2.27). CONCLUSIONS: We believe that excision of the
      deep fascia does not improve the outcome of melanomas thicker than 2 mm.

PMID- 25392907
TI  - Accumulation of terpenoid phytoalexins in maize roots is associated with drought
      tolerance.
AB  - Maize (Zea mays) production, which is of global agro-economic importance, is
      largely limited by herbivore pests, pathogens and environmental conditions, such
      as drought. Zealexins and kauralexins belong to two recently identified families
      of acidic terpenoid phytoalexins in maize that mediate defence against both
      pathogen and insect attacks in aboveground tissues. However, little is known
      about their function in belowground organs and their potential to counter abiotic
      stress. In this study, we show that zealexins and kauralexins accumulate in roots
      in response to both biotic and abiotic stress including, Diabrotica balteata
      herbivory, Fusarium verticillioides infection, drought and high salinity. We find
      that the quantity of drought-induced phytoalexins is positively correlated with
      the root-to-shoot ratio of different maize varieties, and further demonstrate
      that mutant an2 plants deficient in kauralexin production are more sensitive to
      drought. The induction of phytoalexins in response to drought is root specific
      and does not influence phytoalexin levels aboveground; however, the accumulation
      of phytoalexins in one tissue may influence the induction capacity of other
      tissues.

PMID- 25392909
TI  - The impact of copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition in
      fullerene chemistry.
AB  - Click reactions largely cross the borders of organic synthetic chemistry and are
      now at the forefront of many interdisciplinary studies at the interfaces between
      chemistry, physics, and biology. As part of this research, our group is involved
      in a program on the development of clickable fullerene building blocks and their
      application in the preparation of a large variety of new advanced materials and
      bioactive compounds. Importantly, the introduction of the click chemistry concept
      in fullerene chemistry allowed us to produce compounds that would barely be
      accessible by using the classical tools of fullerene chemistry. This is
      particularly the case for the conjugation of fullerenes with other carbon
      nanoforms, such as carbon nanohorns and graphene. It is also the case for most of
      the sophisticated molecular ensembles constructed from clickable fullerene hexa
      adduct building blocks. In this paper, we have summarized our ongoing progress in
      this particular field.

PMID- 25392908
TI  - A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis
      without hemolytic anemia.
AB  - Aldolase A deficiency has been reported as a rare cause of hemolytic anemia
      occasionally associated with myopathy. We identified a deleterious homozygous
      mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without
      hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We
      show that the underlying mechanism involves an exacerbation of aldolase A
      deficiency at high temperatures that affected myoblasts but not erythrocytes. The
      aldolase A deficiency was rescued by arginine supplementation in vitro but not by
      glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting
      that arginine-mediated rescue operated by a mechanism other than protein
      chaperoning. Lipid droplets accumulated in patient myoblasts relative to control
      and this was increased by cytokines, and reduced by dexamethasone. Our results
      expand the clinical spectrum of aldolase A deficiency to isolated temperature
      dependent rhabdomyolysis, and suggest that thermolability may be tissue specific.
      We also propose a treatment for this severe disease. 

PMID- 25392910
TI  - Quality and age of shallow groundwater in the Bakken Formation production area,
      Williston Basin, Montana and North Dakota.
AB  - The quality and age of shallow groundwater in the Bakken Formation production
      area were characterized using data from 30 randomly distributed domestic wells
      screened in the upper Fort Union Formation. Comparison of inorganic and organic
      chemical concentrations to health based drinking-water standards, correlation
      analysis of concentrations with oil and gas well locations, and isotopic data
      give no indication that energy-development activities affected groundwater
      quality. It is important, however, to consider these results in the context of
      groundwater age. Most samples were recharged before the early 1950s and had 14C
      ages ranging from <1000 to >30,000 years. Thus, domestic wells may not be as well
      suited for detecting contamination associated with recent surface spills as
      shallower wells screened near the water table. Old groundwater could be
      contaminated directly by recent subsurface leaks from imperfectly cemented oil
      and gas wells, but horizontal groundwater velocities calculated from 14C ages
      imply that the contaminants would still be less than 0.5 km from their source.
      For the wells sampled in this study, the median distance to the nearest oil and
      gas well was 4.6 km. Because of the slow velocities, a long-term commitment to
      groundwater monitoring in the upper Fort Union Formation is needed to assess the
      effects of energy development on groundwater quality. In conjunction with that
      effort, monitoring could be done closer to energy-development activities to
      increase the likelihood of early detection of groundwater contamination if it did
      occur.

PMID- 25392911
TI  - Optimized UV detection of high-concentration antibody formulations using high
      throughput SE-HPLC.
AB  - High-concentration antibody solutions (>100 mg/mL) present significant challenges
      for formulation and process development, including formulation attributes such as
      increased solution viscosity, and the propensity for self-association. An
      additional challenge comes from the adaptation of analytical methods designed for
      low-concentration formulations to the high-concentration regime. The oligomeric
      state is a good example: it is a quality attribute monitored during
      pharmaceutical development and is one that can be affected by dilution; a typical
      first step in the analysis of high-concentration solutions. The objective of this
      work was to develop a size-exclusion HPLC (SE-HPLC) method that would allow the
      injection of high-concentration antibody formulations without the need for
      dilution prior to injection and their analysis in a high-throughput manner that
      does not create a bottleneck for the execution of complex formulation development
      studies. It was found that changing the UV detection wavelength from 215 to 235
      nm simplified sample preparation by allowing for an approximately fivefold
      increase in injection load while maintaining the signal within the linear range
      of detection. In addition, the chromatographic peak properties (i.e., peak
      symmetry, resolution, and sensitivity) were determined to be consistent when
      compared with analytical methods developed for formulations with lower antibody
      concentrations.

PMID- 25392912
TI  - High phylogenetic diversity of glycosyl hydrolase family 10 and 11 xylanases in
      the sediment of Lake Dabusu in China.
AB  - Soda lakes are one of the most stable naturally occurring alkaline and saline
      environments, which harbor abundant microorganisms with diverse functions. In
      this study, culture-independent molecular methods were used to explore the
      genetic diversity of glycoside hydrolase (GH) family 10 and GH11 xylanases in
      Lake Dabusu, a soda lake with a pH value of 10.2 and salinity of 10.1%. A total
      of 671 xylanase gene fragments were obtained, representing 78 distinct GH10 and
      28 GH11 gene fragments respectively, with most of them having low homology with
      known sequences. Phylogenetic analysis revealed that the GH10 xylanase sequences
      mainly belonged to Bacteroidetes, Proteobacteria, Actinobacteria, Firmicutes and
      Verrucomicrobia, while the GH11 sequences mainly consisted of Actinobacteria,
      Firmicutes and Fungi. A full-length GH10 xylanase gene (xynAS10-66) was directly
      cloned and expressed in Escherichia coli, and the recombinant enzymes showed high
      activity at alkaline pH. These results suggest that xylanase gene diversity
      within Lake Dabusu is high and that most of the identified genes might be novel,
      indicating great potential for applications in industry and agriculture. 

PMID- 25392914
TI  - Restriction of Francisella novicida genetic diversity during infection of the
      vector midgut.
AB  - The genetic diversity of pathogens, and interactions between genotypes, can
      strongly influence pathogen phenotypes such as transmissibility and virulence.
      For vector-borne pathogens, both mammalian hosts and arthropod vectors may limit
      pathogen genotypic diversity (number of unique genotypes circulating in an area)
      by preventing infection or transmission of particular genotypes. Mammalian hosts
      often act as "ecological filters" for pathogen diversity, where novel variants
      are frequently eliminated because of stochastic events or fitness costs. However,
      whether vectors can serve a similar role in limiting pathogen diversity is less
      clear. Here we show using Francisella novicida and a natural tick vector of
      Francisella spp. (Dermacentor andersoni), that the tick vector acted as a
      stronger ecological filter for pathogen diversity compared to the mammalian host.
      When both mice and ticks were exposed to mixtures of F. novicida genotypes,
      significantly fewer genotypes co-colonized ticks compared to mice. In both ticks
      and mice, increased genotypic diversity negatively affected the recovery of
      available genotypes. Competition among genotypes contributed to the reduction of
      diversity during infection of the tick midgut, as genotypes not recovered from
      tick midguts during mixed genotype infections were recovered from tick midguts
      during individual genotype infection. Mediated by stochastic and selective
      forces, pathogen genotype diversity was markedly reduced in the tick. We
      incorporated our experimental results into a model to demonstrate how vector
      population dynamics, especially vector-to-host ratio, strongly affected pathogen
      genotypic diversity in a population over time. Understanding pathogen genotypic
      population dynamics will aid in identification of the variables that most
      strongly affect pathogen transmission and disease ecology. 

PMID- 25392913
TI  - Global disease monitoring and forecasting with Wikipedia.
AB  - Infectious disease is a leading threat to public health, economic stability, and
      other key social structures. Efforts to mitigate these impacts depend on accurate
      and timely monitoring to measure the risk and progress of disease. Traditional,
      biologically-focused monitoring techniques are accurate but costly and slow; in
      response, new techniques based on social internet data, such as social media and
      search queries, are emerging. These efforts are promising, but important
      challenges in the areas of scientific peer review, breadth of diseases and
      countries, and forecasting hamper their operational usefulness. We examine a
      freely available, open data source for this use: access logs from the online
      encyclopedia Wikipedia. Using linear models, language as a proxy for location,
      and a systematic yet simple article selection procedure, we tested 14 location
      disease combinations and demonstrate that these data feasibly support an approach
      that overcomes these challenges. Specifically, our proof-of-concept yields models
      with r2 up to 0.92, forecasting value up to the 28 days tested, and several pairs
      of models similar enough to suggest that transferring models from one location to
      another without re-training is feasible. Based on these preliminary results, we
      close with a research agenda designed to overcome these challenges and produce a
      disease monitoring and forecasting system that is significantly more effective,
      robust, and globally comprehensive than the current state of the art.

PMID- 25392915
TI  - Persisting social participation restrictions among former Buruli ulcer patients
      in Ghana and Benin.
AB  - BACKGROUND: Buruli ulcer may induce severe disabilities impacting on a person's
      well-being and quality of life. Information about long-term disabilities and
      participation restrictions is scanty. The objective of this study was to gain
      insight into participation restrictions among former Buruli ulcer patients in
      Ghana and Benin. METHODS: In this cross-sectional study, former Buruli ulcer
      patients were interviewed using the Participation Scale, the Buruli Ulcer
      Functional Limitation Score to measure functional limitations, and the
      Explanatory Model Interview Catalogue to measure perceived stigma. Healthy
      community controls were also interviewed using the Participation Scale. Trained
      native interviewers conducted the interviews. Former Buruli ulcer patients were
      eligible for inclusion if they had been treated between 2005 and 2011, had ended
      treatment at least 3 months before the interview, and were at least 15 years of
      age. RESULTS: In total, 143 former Buruli ulcer patients and 106 community
      controls from Ghana and Benin were included in the study. Participation
      restrictions were experienced by 67 former patients (median score, 30, IQR;
      23;43) while 76 participated in social life without problems (median score 5,
      IQR; 2;9). Most restrictions encountered related to employment. Linear regression
      showed being female, perceived stigma, functional limitations, and larger lesions
      (category II) as predictors of more participation restrictions. CONCLUSION:
      Persisting participation restrictions were experienced by former BU patients in
      Ghana and Benin. Most important predictors of participation restrictions were
      being female, perceived stigma, functional limitations and larger lesions.

PMID- 25392916
TI  - Ca2+-induced PRE-NMR changes in the troponin complex reveal the possessive nature
      of the cardiac isoform for its regulatory switch.
AB  - The interaction between myosin and actin in cardiac muscle, modulated by the
      calcium (Ca2+) sensor Troponin complex (Tn), is a complex process which is yet to
      be fully resolved at the molecular level. Our understanding of how the binding of
      Ca2+ triggers conformational changes within Tn that are subsequently propagated
      through the contractile apparatus to initiate muscle activation is hampered by a
      lack of an atomic structure for the Ca2+-free state of the cardiac isoform. We
      have used paramagnetic relaxation enhancement (PRE)-NMR to obtain a description
      of the Ca2+-free state of cardiac Tn by describing the movement of key regions of
      the troponin I (cTnI) subunit upon the release of Ca2+ from Troponin C (cTnC).
      Site-directed spin-labeling was used to position paramagnetic spin labels in cTnI
      and the changes in the interaction between cTnI and cTnC subunits were then
      mapped by PRE-NMR. The functionally important regions of cTnI targeted in this
      study included the cTnC-binding N-region (cTnI57), the inhibitory region
      (cTnI143), and two sites on the regulatory switch region (cTnI151 and cTnI159).
      Comparison of 1H-15N-TROSY spectra of Ca2+-bound and free states for the spin
      labeled cTnC-cTnI binary constructs demonstrated the release and modest movement
      of the cTnI switch region (~10 A) away from the hydrophobic N-lobe of troponin C
      (cTnC) upon the removal of Ca2+. Our data supports a model where the non-bound
      regulatory switch region of cTnI is highly flexible in the absence of Ca2+ but
      remains in close vicinity to cTnC. We speculate that the close proximity of TnI
      to TnC in the cardiac complex is favourable for increasing the frequency of
      collisions between the N-lobe of cTnC and the regulatory switch region,
      counterbalancing the reduction in collision probability that results from the
      incomplete opening of the N-lobe of TnC that is unique to the cardiac isoform. 

PMID- 25392918
TI  - Gastrointestinal: esophageal traction diverticulum led to tuberculosis diagnosis.

PMID- 25392917
TI  - Gastrointestinal: rare and almost fatal case of upper gastrointestinal bleeding.

PMID- 25392919
TI  - Gastrointestinal: endoscopic treatment of an infected pancreatic pseudocyst post
      insertion of a covered self-expandable metal stent (CSEMS).

PMID- 25392920
TI  - Hepatology: hepatocellular carcinoma in a young man secondary to androgenic
      anabolic steroid abuse.

PMID- 25392921
TI  - Hepatology: Fitz-Hugh-Curtis syndrome: pelvic inflammatory disease with
      perihepatitis.

PMID- 25392922
TI  - Immunoglobulin expressions are only associated with MCPyV-positive Merkel cell
      carcinomas but not with MCPyV-negative ones: comparison of prognosis.
AB  - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, often
      associated with Merkel cell polyomavirus (MCPyV). Recently, immunoglobulin (Ig)
      expression was reported in MCC, thereby suggesting that B cells might be their
      cellular ancestors. We tested 30 MCCs (20 MCPyV-positive and 10 MCPyV-negative)
      using immunohistochemistry for the expressions of IgG, IgA, IgM, Igkappa,
      Iglambda, terminal desoxynucleotidyl transferase, paired box gene 5 (PAX5),
      octamer transcription factor-2 (Oct-2), and sex-determining region Y-box 11
      (SOX11). We performed in situ hybridization for Igkappa-mRNA or Iglambda-mRNA and
      Ig heavy chain (IgH) gene rearrangement (IgH-R) analyses. The expressions of
      PAX5, TdT, Oct-2, and SOX11 were not significantly different between MCPyV
      positive and MCPyV-negative MCCs. At least 1 of IgG, IgA, IgM, or Igkappa was
      expressed in MCPyV-positive (14/20, 70%) and none in MCPyV-negative MCCs
      (P=0.0003). There was a higher tendency for Igkappa-mRNA expression (7/19, using
      in situ hybridization) and IgH-R (10/20, using polymerase chain reaction) in
      MCPyV-positive than in MCPyV-negative MCCs (0/10 and 2/10, respectively), thus
      suggesting a different Ig production pattern and pathogenesis between the 2 types
      of MCC. Ig expression or IgH-R in MCPyV-positive MCCs might be associated with
      MCPyV gene integration or expression in cancer cells but do not necessarily
      suggest a B-cell origin for MCCs. IgH expression or IgH-R nonsignificantly
      correlated with improved prognosis. However, these might be important factors
      that influence the survival of neoplastic cells and might allow the development
      of novel therapies for patients with MCPyV-positive MCCs. 

PMID- 25392923
TI  - Surgical resection margins in desmoid-type fibromatosis: a critical reassessment.
AB  - The prognostic value of surgical resection margins in predicting recurrence of
      desmoid-type fibromatosis remains inconclusive, and appropriate resection margins
      are not defined. We analyzed whether specific factors related to margin status,
      including the adequacy of pathologic assessment, affect the prognostic impact of
      surgical resection margins in a retrospective cohort study. The distance
      (clearance) and tissue composition of resection margins were recorded for primary
      desmoid resections with negative margins. The number of positive margins and the
      linear extent of marginal involvement were recorded for cases with positive
      margins. The number of tissue sections submitted for histopathologic evaluation
      of resection margins was also noted. Factors predictive of a positive margin and
      local recurrence were evaluated by logistic regression and survival analyses. The
      probability of documenting a positive margin increased with the number of tissue
      sections submitted for assessment of margin status (odds ratio 1.16; P=0.007).
      Recurrence-free survival at 10 years for patients with positive (N=52) or
      negative (N=40) resection margins was 68% and 60%, respectively. Only tumor
      clearance was predictive of local recurrence. A positive or close (<1 mm)
      resection margin was an independent prognostic factor for local recurrence in a
      multivariate Cox regression model accounting for patient age and anatomic site
      (hazard ratio 9.52; P=0.028). Surgical resection margin status, as currently
      evaluated and reported, fails to predict recurrence-free survival for desmoid
      tumors. Instead, positive or close (<1 mm) resection margins are predictive of
      disease recurrence. In addition, multiple targeted sections are necessary for
      accurate assessment of surgical resection margins of desmoid-type fibromatosis. 

PMID- 25392924
TI  - Human adipose-derived mesenchymal stem cells as a new model of spinal and bulbar
      muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease is an X-linked
      CAG/polyglutamine expansion motoneuron disease, in which an elongated
      polyglutamine tract (polyQ) in the N-terminal androgen receptor (ARpolyQ) confers
      toxicity to this protein. Typical markers of SBMA disease are ARpolyQ
      intranuclear inclusions. These are generated after the ARpolyQ binds to its
      endogenous ligands, which promotes AR release from chaperones, activation and
      nuclear translocation, but also cell toxicity. The SBMA mouse models developed so
      far, and used in preclinical studies, all contain an expanded CAG repeat
      significantly longer than that of SBMA patients. Here, we propose the use of SBMA
      patients adipose-derived mesenchymal stem cells (MSCs) as a new human in vitro
      model to study ARpolyQ toxicity. These cells have the advantage to express only
      ARpolyQ, and not the wild type AR allele. Therefore, we isolated and
      characterized adipose-derived MSCs from three SBMA patients (ADSC from Kennedy's
      patients, ADSCK) and three control volunteers (ADSCs). We found that both ADSCs
      and ADSCKs express mesenchymal antigens, even if only ADSCs can differentiate
      into the three typical cell lineages (adipocytes, chondrocytes and osteocytes),
      whereas ADSCKs, from SBMA patients, showed a lower growth potential and
      differentiated only into adipocyte. Moreover, analysing AR expression on our
      mesenchymal cultures we found lower levels in all ADSCKs than ADSCs, possibly
      related to negative pressures exerted by toxic ARpolyQ in ADSCKs. In addition,
      with proteasome inhibition the ARpolyQ levels increased specifically in ADSCKs,
      inducing the formation of HSP70 and ubiquitin positive nuclear ARpolyQ
      inclusions. Considering all of this evidence, SBMA patients adipose-derived MSCs
      cultures should be considered an innovative in vitro human model to understand
      the molecular mechanisms of ARpolyQ toxicity and to test novel therapeutic
      approaches in SBMA. 

PMID- 25392925
TI  - Vaccine-induced protection of rhesus macaques against plasma viremia after
      intradermal infection with a European lineage 1 strain of West Nile virus.
AB  - The mosquito-borne West Nile virus (WNV) causes human and animal disease with
      outbreaks in several parts of the world including North America, the
      Mediterranean countries, Central and East Europe, the Middle East, and Africa.
      Particularly in elderly people and individuals with an impaired immune system,
      infection with WNV can progress into a serious neuroinvasive disease. Currently,
      no treatment or vaccine is available to protect humans against infection or
      disease. The goal of this study was to develop a WNV-vaccine that is safe to use
      in these high-risk human target populations. We performed a vaccine efficacy
      study in non-human primates using the contemporary, pathogenic European WNV
      genotype 1a challenge strain, WNV-Ita09. Two vaccine strategies were evaluated in
      rhesus macaques (Macaca mulatta) using recombinant soluble WNV envelope (E)
      ectodomain adjuvanted with Matrix-M, either with or without DNA priming. The DNA
      priming immunization was performed with WNV-DermaVir nanoparticles. Both
      vaccination strategies successfully induced humoral and cellular immune responses
      that completely protected the macaques against the development of viremia. In
      addition, the vaccine was well tolerated by all animals. Overall, The WNV E
      protein adjuvanted with Matrix-M is a promising vaccine candidate for a non
      infectious WNV vaccine for use in humans, including at-risk populations. 

PMID- 25392927
TI  - Assessment of a Cambridge Structural Database-driven overlay program.
AB  - We recently published an improved methodology for overlaying multiple flexible
      ligands and an extensive data set for validating pharmacophore programs. Here, we
      combine these two developments and present evidence of the effectiveness of the
      new overlay methodology at predicting correct superimpositions for systems with
      varying levels of complexity. The overlay program was able to generate correct
      predictions for 95%, 73%, and 39% of systems classified as easy, moderate, and
      hard, respectively. 

PMID- 25392926
TI  - Elevated soluble CD163 plasma levels are associated with disease severity in
      patients with hemorrhagic fever with renal syndrome.
AB  - BACKGROUND: Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic
      fever with renal syndrome (HFRS). Although HFRS pathogenesis has not been
      entirely elucidated, the importance of host-related immune responses in HFRS
      pathogenesis has been widely recognized. CD163, a monocyte and macrophage
      specific scavenger receptor that plays a vital function in the hosts can reduce
      inflammation, is shed during activation as soluble CD163 (sCD163). The aim of
      this study was to investigate the pathological significance of sCD163 in patients
      with HFRS. METHODS: Blood samples were collected from 81 hospitalized patients in
      Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls.
      The sCD163 plasma levels were measured using a sandwich ELISA, and the
      relationship between sCD163 and disease severity was analyzed. Furthermore, CD163
      expression in 3 monocytes subset was analyzed by flow cytometry. RESULTS: The
      results demonstrated that sCD163 plasma levels during the HFRS acute phase were
      significantly higher in patients than during the convalescent stage and the
      levels in the healthy controls (P<0.0001). The sCD163 plasma levels in the
      severe/critical group were higher than those in the mild/moderate group during
      the acute (P<0.0001). A Spearman correlation analysis indicated that the sCD163
      levels were positively correlated with white blood cell, serum creatine, blood
      urea nitrogen levels, while they were negatively correlated with blood platelet
      levels in the HFRS patients. The monocyte subsets were significantly altered
      during the acute stage. Though the CD163 expression levels within the monocyte
      subsets were increased during the acute stage, the highest CD163 expression level
      was observed in the CD14++CD16+ monocytes when compared with the other monocyte
      subsets. CONCLUSION: sCD163 may be correlated with disease severity and the
      disease progression in HFRS patients; however, the underlying mechanisms should
      be explored further.

PMID- 25392928
TI  - Different structural properties of high-amylose maize starch fractions varying in
      granule size.
AB  - Large-, medium-, and small-sized granules were separated from normal and high
      amylose maize starches using a glycerol centrifugation method. The different
      sized fractions of normal maize starch showed similar molecular weight
      distribution, crystal structure, long- and short-range ordered structure, and
      lamellar structure of starch, but the different-sized fractions of high-amylose
      maize starch showed markedly different structural properties. The amylose
      content, iodine blue value, amylopectin long branch-chain, and IR ratio of
      1045/1022 cm(-1) significantly increased with decrease of granule size, but the
      amylopectin short branch-chain and branching degree, relative crystallinity, IR
      ratio of 1022/995 cm(-1), and peak intensity of lamellar structure markedly
      decreased with decrease of granule size for high-amylose maize starch. The large
      sized granules of high-amylose maize starch were A-type crystallinity, native and
      medium-sized granules of high-amylose maize starch were CA-type crystallinity,
      and small-sized granules of high-amylose maize starch were C-type crystallinity,
      indicating that C-type starch might contain A-type starch granules. 

PMID- 25392929
TI  - Gait analysis in a Mecp2 knockout mouse model of Rett syndrome reveals early
      onset and progressive motor deficits.
AB  - Rett syndrome (RTT) is a genetic disorder characterized by a range of features
      including cognitive impairment, gait abnormalities and a reduction in purposeful
      hand skills. Mice harbouring knockout mutations in the Mecp2 gene display many
      RTT-like characteristics and are central to efforts to find novel therapies for
      the disorder. As hand stereotypies and gait abnormalities constitute major
      diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes
      will be of importance in assessing preclinical therapeutic outcomes. We therefore
      aimed to assess gait properties over the prodromal phase in a functional knockout
      mouse model of RTT. In male Mecp2 knockout mice, we observed alterations in
      stride, coordination and balance parameters at 4 weeks of age, before the onset
      of other overt phenotypic changes as revealed by observational scoring. These
      data suggest that gait measures may be used as a robust and early marker of MeCP2
      dysfunction in future preclinical therapeutic studies. 

PMID- 25392930
TI  - Genome-wide microarray expression and genomic alterations by array-CGH analysis
      in neuroblastoma stem-like cells.
AB  - Neuroblastoma has a very diverse clinical behaviour: from spontaneous regression
      to a very aggressive malignant progression and resistance to chemotherapy. This
      heterogeneous clinical behaviour might be due to the existence of Cancer Stem
      Cells (CSC), a subpopulation within the tumor with stem-like cell properties: a
      significant proliferation capacity, a unique self-renewal capacity, and
      therefore, a higher ability to form new tumors. We enriched the CSC-like cell
      population content of two commercial neuroblastoma cell lines by the use of
      conditioned cell culture media for neurospheres, and compared genomic gains and
      losses and genome expression by array-CGH and microarray analysis, respectively
      (in CSC-like versus standard tumor cells culture). Despite the array-CGH did not
      show significant differences between standard and CSC-like in both analyzed cell
      lines, the microarray expression analysis highlighted some of the most relevant
      biological processes and molecular functions that might be responsible for the
      CSC-like phenotype. Some signalling pathways detected seem to be involved in self
      renewal of normal tissues (Wnt, Notch, Hh and TGF-beta) and contribute to CSC
      phenotype. We focused on the aberrant activation of TGF-beta and Hh signalling
      pathways, confirming the inhibition of repressors of TGF-beta pathway, as SMAD6
      and SMAD7 by RT-qPCR. The analysis of the Sonic Hedgehog pathway showed
      overexpression of PTCH1, GLI1 and SMO. We found overexpression of CD133 and CD15
      in SIMA neurospheres, confirming that this cell line was particularly enriched in
      stem-like cells. This work shows a cross-talk among different pathways in
      neuroblastoma and its importance in CSC-like cells. 

PMID- 25392931
TI  - Influenza vaccine effectiveness in preventing influenza A(H3N2)-related
      hospitalizations in adults targeted for vaccination by type of vaccine: a
      hospital-based test-negative study, 2011-2012 A(H3N2) predominant influenza
      season, Valencia, Spain.
AB  - BACKGROUND: Most evidence of the effectiveness of influenza vaccines comes from
      studies conducted in primary care, but less is known about their effectiveness in
      preventing serious complications. Here, we examined the influenza vaccine
      effectiveness (IVE) against hospitalization with PCR-confirmed influenza in the
      predominant A(H3N2) 2011-2012 influenza season. METHODS: A hospital-based, test
      negative study was conducted in nine hospitals in Valencia, Spain. All emergency
      admissions with a predefined subset of symptoms were eligible. We enrolled
      consenting adults age 18 and over, targeted for influenza vaccination because of
      comorbidity, with symptoms of influenza-like-illness within seven days of
      admission. We estimated IVE as (1-adjusted vaccination odds ratio)*100 after
      accounting for major confounders, calendar time and recruitment hospital.
      RESULTS: The subjects included 544 positive for influenza A(H3N2) and 1,370
      negative for influenza admissions. Age was an IVE modifying factor. Regardless of
      vaccine administration, IVE was 72% (38 to 88%) in subjects aged under 65 and 21%
      (-5% to 40%) in subjects aged 65 and over. By type of vaccine, the IVE of
      classical intramuscular split-influenza vaccine, used in subjects 18 to 64, was
      68% (12% to 88%). The IVE for intradermal and virosomal influenza vaccines, used
      in subjects aged 65 and over, was 39% (11% to 58%) and 16% (-39% to 49%),
      respectively. CONCLUSIONS: The split-influenza vaccine was effective in
      preventing influenza-associated hospitalizations in adults aged under 65. The
      intradermal vaccine was moderately effective in those aged 65 and over.

PMID- 25392932
TI  - RNA processing factors Swd2.2 and Sen1 antagonize RNA Pol III-dependent
      transcription and the localization of condensin at Pol III genes.
AB  - Condensin-mediated chromosome condensation is essential for genome stability upon
      cell division. Genetic studies have indicated that the association of condensin
      with chromatin is intimately linked to gene transcription, but what transcription
      associated feature(s) direct(s) the accumulation of condensin remains unclear.
      Here we show in fission yeast that condensin becomes strikingly enriched at RNA
      Pol III-transcribed genes when Swd2.2 and Sen1, two factors involved in the
      transcription process, are simultaneously deleted. Sen1 is an ATP-dependent
      helicase whose orthologue in Saccharomyces cerevisiae contributes both to
      terminate transcription of some RNA Pol II transcripts and to antagonize the
      formation of DNA:RNA hybrids in the genome. Using two independent mapping
      techniques, we show that DNA:RNA hybrids form in abundance at Pol III-transcribed
      genes in fission yeast but we demonstrate that they are unlikely to faciliate the
      recruitment of condensin. Instead, we show that Sen1 forms a stable and abundant
      complex with RNA Pol III and that Swd2.2 and Sen1 antagonize both the interaction
      of RNA Pol III with chromatin and RNA Pol III-dependent transcription. When
      Swd2.2 and Sen1 are lacking, the increased concentration of RNA Pol III and
      condensin at Pol III-transcribed genes is accompanied by the accumulation of
      topoisomerase I and II and by local nucleosome depletion, suggesting that Pol III
      transcribed genes suffer topological stress. We provide evidence that this
      topological stress contributes to recruit and/or stabilize condensin at Pol III
      transcribed genes in the absence of Swd2.2 and Sen1. Our data challenge the idea
      that a processive RNA polymerase hinders the binding of condensin and suggest
      that transcription-associated topological stress could in some circumstances
      facilitate the association of condensin. 

PMID- 25392934
TI  - Catatonia in outpatients: analysis of a single clinical practice.

PMID- 25392935
TI  - Dimenhydrinate use disorder with chronic psychosis.

PMID- 25392933
TI  - Galectin-1 exerts inhibitory effects during DENV-1 infection.
AB  - Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and
      can infect a variety of immune and non-immune cells. Response to infection ranges
      from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever.
      Despite efforts to control the disease, there are no effective treatments or
      vaccines. In our search for new antiviral compounds to combat infection by dengue
      virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed
      mammalian lectin with functions in cell-pathogen interactions and
      immunoregulatory properties. We found that DENV-1 infection of cells in vitro
      exhibited caused decreased expression of Gal-1 in several different human cell
      lines, suggesting that loss of Gal-1 is associated with virus production. In test
      of this hypothesis we found that exogenous addition of human recombinant Gal-1
      (hrGal-1) inhibits the virus production in the three different cell types. This
      inhibitory effect was dependent on hrGal-1 dimerization and required its
      carbohydrate recognition domain. Importantly, the inhibition was specific for
      hrGal-1, since no effect was observed using recombinant human galectin-3.
      Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at
      least in part, during the early stages of DENV-1 infection, by inhibiting viral
      adsorption and its internalization to target cells. To test the in vivo role of
      Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the
      expression of endogenous Galectin-1 contributes to resistance of macrophages to
      in vitro-infection with DENV-1 and it is also important to physiological
      susceptibility of mice to in vivo infection with DENV-1. These results provide
      novel insights into the functions of Gal-1 in resistance to DENV infection and
      suggest that Gal-1 should be explored as a potential antiviral compound. 

PMID- 25392937
TI  - Bacillus subtilis spore display of laccase for evolution under extreme conditions
      of high concentrations of organic solvent.
AB  - Protein libraries were displayed on the spore coat of Bacillus subtilis, and this
      method was demonstrated as a tool for directed evolution under extreme
      conditions. Escherichia coli, yeast, and phage display suffer from protein
      folding, and viability issues. On the other hand, spores avoid folding concerns
      by the natural sporulation process, and they remain viable under harsh chemical
      and physical environments. The naturally occurring B. subtilis spore coat
      protein, CotA, was evolved for improved activity under conditions of high organic
      solvent concentrations. CotA is a laccase, which is a copper-containing oxidase
      enzyme. A CotA library was expressed on the spore coat, and ~ 3000 clones were
      screened at 60% dimethyl sulfoxide (DMSO). A Thr480Ala variant (Thr480Ala-CotA)
      was identified that was 2.38-fold more active than the wild-type CotA. In
      addition, Thr480Ala-CotA was more active with different concentrations of DMSO
      ranging from 0 to 70%. The mutant was also found to be more active compared with
      the wild-type CotA in different concentrations of methanol, ethanol, and
      acetonitrile.

PMID- 25392936
TI  - The urinary cytokine/chemokine signature of renal hyperfiltration in adolescents
      with type 1 diabetes.
AB  - OBJECTIVE: Urinary cytokine/chemokine levels are elevated in adults with type 1
      diabetes (T1D) exhibiting renal hyperfiltration. Whether this observation extends
      to adolescents with T1D remains unknown. Our first objective was to determine the
      relationship between hyperfiltration and urinary cytokines/chemokines in
      normotensive, normoalbuminuric adolescents with T1D using GFR(cystatin). Our
      second aim was to determine the relationship between urine and plasma levels of
      inflammatory biomarkers, to clarify the origin of these factors. METHODS: Urine
      and serum cytokines/chemokines (Luminex platform) and GFR(cystatin) were measured
      in normofiltering (n = 111, T1D-N, GFR<135 ml/min/1.73 m(2)) and hyperfiltering
      (n = 31, T1D-H, GFR >= 135 ml/min/1.73 m(2)) adolescents with T1D (ages 10-16),
      and in age and sex matched healthy control subjects (HC, n = 59). RESULTS: We
      noted significant step-wise increases in urinary cytokine/chemokine excretion
      according to filtration status with highest levels in T1D-H, with parallel trends
      in serum analyte concentrations. After adjusting for serum glucose at the time of
      sampling, differences in urinary cytokine excretion were not statistically
      significant. Only serum IL-2 significantly differed between HC and T1D (p =
      0.0076). CONCLUSIONS: Hyperfiltration is associated with increased urinary
      cytokine/chemokine excretion in T1D adolescents, and parallel trends in serum
      cytokine concentration. The GFR-associated trends in cytokine excretion may be
      driven by the effects of ambient hyperglycemia. The relationship between
      hyperfiltration, glycemia, and variations in serum and urine cytokine expression
      and their impact on future renal and systemic vascular complications requires
      further study.

PMID- 25392938
TI  - MRI quantification of non-Gaussian water diffusion in normal human kidney: a
      diffusional kurtosis imaging study.
AB  - Our aim was to prospectively evaluate the feasibility of diffusional kurtosis
      imaging (DKI) in normal human kidney and to report preliminary DKI measurements.
      Institutional review board approval and informed consent were obtained. Forty-two
      healthy volunteers underwent diffusion-weighted imaging (DWI) scans with a 3-T MR
      scanner. b values of 0, 500 and 1000 s/mm(2) were adopted. Maps of fractional
      anisotropy (FA), mean diffusivity (MD), radial diffusivity (D?), axial
      diffusivity (D||), mean kurtosis (MK), radial kurtosis (K?) and axial kurtosis
      (K||) were produced. Three representative axial slices in the upper pole, mid
      zone and lower pole were selected in the left and right kidney. On each selected
      slice, three regions of interest were drawn on the renal cortex and another three
      on the medulla. Statistical comparison was performed with t-test and analysis of
      variance. Thirty-seven volunteers successfully completed the scans. No
      statistically significant differences were observed between the left and right
      kidney for all metrics (p values in the cortex: FA, 0.114; MD, 0.531; D?, 0.576;
      D||, 0.691; MK, 0.934; K?, 0.722; K||, 0.891; p values in the medulla: FA, 0.348;
      MD, 0.732; D?, 0.470; D||, 0.289; MK, 0.959; K?, 0.780; K||, 0.287). Kurtosis
      metrics (MK, K||, K?) obtained in the renal medulla were significantly (p <0.001)
      higher than those in the cortex (0.552 +/- 0.04, 0.637 +/- 0.07 and 0.530 +/-
      0.08 in the medulla and 0.373 +/- 0.04, 0.492 +/- 0.06 and 0.295 +/- 0.06 in the
      cortex, respectively). For the diffusivity measures, FA of the medulla (0.356 +/-
      0.03) was higher than that of the cortex (0.179 +/- 0.03), whereas MD, D? and D||
      (mm(2) /ms) were lower in the medulla than in the cortex (3.88 +/- 0.09, 3.50 +/-
      0.23 and 4.65 +/- 0.29 in the cortex and 2.88 +/- 0.11, 2.32 +/- 0.20 and 3.47 +/
      0.31 in the medulla, respectively). Our results indicate that DKI is feasible in
      the human kidney. We have reported the preliminary DKI measurements of normal
      human kidney that demonstrate well the non-Gaussian behavior of water diffusion,
      especially in the renal medulla.

PMID- 25392939
TI  - Five-meter rope-climbing: a commando-specific power test of the upper limbs.
AB  - PURPOSE: To examine the concurrent validity and absolute and relative
      reliabilities of a commando-specific power test. PARTICIPANTS: 21 antiterrorism
      commandos. METHODS: All participants were assessed on a 5-m rope-climbing test
      (RCT) and the following tests: pull-ups, push-ups, estimated-1-repetition-maximum
      (est-1RM), medicine-ball put, and handgrip-strength test. The stopwatch method
      related to the execution time (ET) was validated by comparison with video motion
      analysis. The best individual attempt of 3 trials was kept for analysis, and the
      performance was expressed in absolute power output (APO) and body-mass relative
      power output (RPO). RESULTS: Stopwatch assessment had an excellent criterion
      validity (r=.99, P<.001), intraclass correlation coefficient (ICC3,1) of .98,
      standard errors of measurement (SEM%) of 1.19%, bias+/-the 95% limits of
      agreement of 0.03+/-0.26 s, and minimal detectable change (MDC95) of 0.51 s. The
      ET, APO, and RPO were significantly correlated (P<.05) with all cited tests
      (absolute-value r range .55-.98), while est-1RM was not significantly correlated
      with the other tests. Test-retest reliability coefficients were excellent for ET,
      APO, and RPO (ICC3,1>.90). The SEM% values for the ET, APO, and RPO were all
      under 5% (range 3.73-4.52%), all being smaller than the corresponding smallest
      worthwhile change. The coefficients of variation for the ET, APO, and RPO were
      all under 10%. %MDC95 ranged from 10.37% to 12.53%. CONCLUSIONS: Considering the
      strong concurrent validity and excellent test-retest reliability, the RCT is
      simple to administer, has ecological validity, and is a valid specific field test
      of upper-body power for commandos and, in addition, can be accurately assessed
      with a stopwatch.

PMID- 25392940
TI  - Rare-earth-metal methyl, amide, and imide complexes supported by a superbulky
      scorpionate ligand.
AB  - The reaction of monomeric [(Tp(tBu,Me) )LuMe2 ] (Tp(tBu,Me) =tris(3-Me-5-tBu
      pyrazolyl)borate) with primary aliphatic amines H2 NR (R=tBu, Ad=adamantyl) led
      to lutetium methyl primary amide complexes [(Tp(tBu,Me) )LuMe(NHR)], the solid
      state structures of which were determined by XRD analyses. The mixed
      methyl/tetramethylaluminate compounds [(Tp(tBu,Me) )LnMe({MU2 -Me}AlMe3 )] (Ln=Y,
      Ho) reacted selectively and in high yield with H2 NR, according to methane
      elimination, to afford heterobimetallic complexes: [(Tp(tBu,Me) )Ln({MU2 
      Me}AlMe2 )(MU2 -NR)] (Ln=Y, Ho). X-ray structure analyses revealed that the
      monomeric alkylaluminum-supported imide complexes were isostructural, featuring
      bridging methyl and imido ligands. Deeper insight into the fluxional behavior in
      solution was gained by (1) H and (13) C NMR spectroscopic studies at variable
      temperatures and (1) H-(89) Y HSQC NMR spectroscopy. Treatment of [(Tp(tBu,Me)
      )LnMe(AlMe4 )] with H2 NtBu gave dimethyl compounds [(Tp(tBu,Me) )LnMe2 ] as
      minor side products for the mid-sized metals yttrium and holmium and in high
      yield for the smaller lutetium. Preparative-scale amounts of complexes
      [(Tp(tBu,Me) )LnMe2 ] (Ln=Y, Ho, Lu) were made accessible through aluminate
      cleavage of [(Tp(tBu,Me) )LnMe(AlMe4 )] with N,N,N',N'-tetramethylethylenediamine
      (tmeda). The solid-state structures of [(Tp(tBu,Me) )HoMe(AlMe4 )] and
      [(Tp(tBu,Me) )HoMe2 ] were analyzed by XRD. 

PMID- 25392941
TI  - Investigation regarding the role of chloride in organic-inorganic halide
      perovskites obtained from chloride containing precursors.
AB  - As the photovoltaic performance of a device is strongly influenced by the
      morphology of perovskite, achieving precise control over the crystal formation of
      organic-inorganic halide perovskites synthesized in the ambience of chloride ions
      has garnered much attention. Although the resulting morphology dictates the
      performance of the device considerably, the understanding of the role of chloride
      ions has been scant. To unravel this mystery, we investigated three different
      organic-inorganic halide perovskite materials grown from the chloride-containing
      precursors under different but optimized conditions. Despite the presence of
      chloride ions in the reaction mixture, scanning transmission electron microscopy-
      energy dispersive spectroscopy (STEM-EDS) reveals that the CH3NH3PbI3 perovskites
      formed are chloride-free. Moreover bright field transmission electron microscopy
      indicates that chloride ions effect the growth of the CH3NH3PbI3. 

PMID- 25392942
TI  - Validation of an LC-MS/MS method for quantitative analysis of the 5 bioactive
      components of Wuzhi capsule in human plasma samples.
AB  - BACKGROUND: Wuzhi capsule (WZC) is an ethanol extract from the ripe fruit of
      Schisandra sphenanthera in traditional Chinese medicine that has long been used
      to treat viral and drug-induced hepatitis in China. The principal active
      components in WZC are Schisandra lignans. The clinical pharmacokinetics of these
      components in the form of an oral WZC preparation is unknown. To optimize the WZC
      dosage and develop WZC-related combination therapies, it is necessary to conduct
      a comprehensive pharmacokinetic study of the Schisandra lignans. METHODS: A
      method was developed for simultaneous quantification of multiple bioactive
      lignans in WZC in human plasma through liquid-liquid extraction followed by
      multiple reaction monitoring liquid chromatography/tandem mass spectrometry with
      positive-mode electrospray ionization. The 5 bioactive constituents were
      separated by isocratic elution using a mobile phase consisting of acetonitrile,
      methanol, and 0.1% aqueous formic acid at a flow rate of 0.3 mL/min. The total
      run time was 3.5 minutes. RESULTS: All analytes showed good linearity over a wide
      concentration range with a lower limit of quantification at 0.5 ng/mL. Using this
      method, we determined the 5 bioactive lignans in WZC from human plasma
      simultaneously and performed a pharmacokinetic study on the Schisandra lignans in
      healthy volunteers. CONCLUSIONS: Owing to simplicity, quickness, high
      sensitivity, and selectivity, and a sufficient lower limit of detection of the
      new liquid chromatography/tandem mass spectrometry method, it may be used as a
      routine technique for clinical monitoring of WZC, and for understanding
      interactions between herbal and conventional drug therapies.

PMID- 25392943
TI  - Advanced renal cell carcinoma in Australia, 2015: what should we do?

PMID- 25392945
TI  - Human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
      (ACMSD): a structural and mechanistic unveiling.
AB  - Human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
      determines the fate of tryptophan metabolites in the kynurenine pathway by
      controlling the quinolinate levels for de novo nicotinamide adenine dinucleotide
      biosynthesis. The unstable nature of its substrate has made gaining insight into
      its reaction mechanism difficult. Our electron paramagnetic resonance (EPR)
      spectroscopic study on the Cu-substituted human enzyme suggests that the native
      substrate does not directly ligate to the metal ion. Substrate binding did not
      result in a change of either the hyperfine structure or the super-hyperfine
      structure of the EPR spectrum. We also determined the crystal structure of the
      human enzyme in its native catalytically active state (at 1.99 A resolution), a
      substrate analogue-bound form (2.50 A resolution), and a selected active site
      mutant form with one of the putative substrate binding residues altered (2.32 A
      resolution). These structures illustrate that each asymmetric unit contains three
      pairs of dimers. Consistent with the EPR findings, the ligand-bound complex
      structure shows that the substrate analogue does not directly coordinate to the
      metal ion but is bound to the active site by two arginine residues through
      noncovalent interactions.

PMID- 25392946
TI  - Minimally invasive thyroid nodulectomy reduces post-operative hypothyroidism when
      compared with thyroid lobectomy.
AB  - BACKGROUND: It has been a long-standing surgical tenet that the minimum surgical
      procedure for a single thyroid nodule is lobectomy. Such an approach, however,
      has been associated with a significant incidence of post-operative hypothyroidism
      with patients becoming medication dependent for life. Thermal sealing devices
      have enabled local nodule excision to be undertaken safely with preservation of
      more residual thyroid mass. The aim of this study was to determine if this
      approach was associated with a reduction in post-operative hypothyroidism.
      METHODS: This is a retrospective cohort study comprising 351 patients treated
      between January 2010 and December 2012. Patients were assessed at 6-8-week
      review. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone
      (TSH) >4.5 mIU/L, with clinical hypothyroidism defined as both an elevated TSH
      and presence of clinical symptoms requiring thyroxine replacement. RESULTS: One
      hundred and ninety patients underwent open thyroid lobectomy, 86 a minimally
      invasive thyroid lobectomy and 75 a minimally invasive nodulectomy. There was no
      difference in post-operative hypothyroidism after lobectomy whether by the open
      (22.1%) or minimally invasive (22.1%) technique. However, after minimally
      invasive nodulectomy, post-operative hypothyroidism was less than one quarter
      (5.3%) of that following lobectomy overall (22.1%, P < 0.01). There were no
      differences in post-operative complications between any of the groups.
      CONCLUSION: Minimally invasive local nodule excision can be performed safely,
      with the potential for significantly reducing the rate of post-operative
      hypothyroidism. As such, the procedure should be considered for appropriately
      selected patients.

PMID- 25392947
TI  - Construction of Matryoshka-type structures from supercharged protein nanocages.
AB  - Designing nanoscaled hierarchical structures with increasing levels of complexity
      is challenging. Here we show that electrostatic interactions between two
      complementarily supercharged protein nanocages can be effectively utilized to
      create nested Matryoshka-type structures. Cage-within-cage complexes containing
      spatially ordered iron oxide nanoparticles spontaneously self-assemble upon
      mixing positively supercharged ferritin compartments with AaLS-13, a larger shell
      forming protein with a negatively supercharged lumen. Exploiting engineered
      Coulombic interactions and protein dynamics in this way opens up new avenues for
      creating hierarchically organized supramolecular assemblies for application as
      delivery vehicles, reaction chambers, and artificial organelles. 

PMID- 25392948
TI  - Enantioselective Friedel-Crafts alkylation of pyrrole with chalcones catalyzed by
      a dinuclear zinc catalyst.
AB  - A highly enantioselective Friedel-Crafts (F-C) alkylation of pyrrole with a wide
      range of simple nonchelating chalcone derivatives catalyzed by a chiral (Zn2EtL)n
      (L = (S,S)-1) complex has been developed. The catalyst (Zn2EtL)n complex was
      prepared in situ by reacting the chiral ligand (S,S)-1 with 2 equiv of
      diethylzinc. A series of beta-pyrrole-substituted dihydrochalcones were usually
      formed mostly in excellent yields (up to 99%) and excellent enantioselectivity
      [up to 99% enantiomeric excess (ee)] by using 15 mol % catalyst loading under
      mild conditions. The absolute stereochemistry of the products was determined to
      be the S-configuration by X-ray crystallographic analysis of 13g. Meanwhile, a
      weak negative nonlinear effect was observed. On the basis of the experimental
      results and previous reports, a possible mechanism was proposed to explain the
      origin of the asymmetric induction. 

PMID- 25392949
TI  - Elucidation of electron ionization induced fragmentations of adenine by
      semiempirical and density functional molecular dynamics.
AB  - The gas phase fragmentation pathways of the nucleobase adenine upon 70 eV
      electron ionization are investigated by means of a combined stochastic and first
      principles based molecular dynamics approach. We employ no preconceived
      fragmentation channels in our calculations, which simulate standard electron
      ionization mass spectrometry (EI-MS) conditions. The reactions observed compare
      well to a wealth of experimental and theoretical data available for this
      important nucleic acid building block. All significant peaks in the experimental
      mass spectrum of adenine are reproduced. Additionally, the fragment ion
      connectivities obtained from our simulations at least partially concur with
      results from previous experimental studies on selectively isotope labeled
      adenines. Moreover, we are able to assign noncyclic structures that are
      entropically favored and have not been proposed in nondynamic quantum chemical
      studies before to the decomposition products, which result automatically from our
      molecular dynamics procedure. From simulations under various conditions it is
      evident that most of the fragmentation reactions even at low internal excess
      energy (<10 eV) occur very fast within a few picoseconds. 

PMID- 25392950
TI  - Presence of neutrophil extracellular traps and citrullinated histone H3 in the
      bloodstream of critically ill patients.
AB  - Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are
      induced by inflammatory stimuli. Modification by citrullination of histone H3 is
      thought to be involved in the in vitro formation of NETs. The purposes of this
      study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are
      present in the bloodstream of critically ill patients and to identify
      correlations with clinical and biological parameters. Blood samples were
      collected from intubated patients at the time of ICU admission from April to June
      2011. To identify NETs, DNA and histone H3 were visualized simultaneously by
      immunofluorescence in blood smears. Cit-H3 was detected using a specific
      antibody. We assessed relationships of the presence of NETs and Cit-H3 with the
      existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and
      concentrations of IL-8, TNF-alpha, cf-DNA, lactate, and HMGB1. Forty-nine
      patients were included. The median of age was 66.0 (IQR: 52.5-76.0) years. The
      diagnoses included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from
      cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4,
      8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We
      identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were
      observed more frequently in "the presence of bacteria in tracheal aspirate" group
      (11/22, 50.0%) than in "the absence of bacteria in tracheal aspirate" group
      (4/27, 14.8%) (p<.01). Multiple logistic regression analysis showed that only the
      presence of bacteria in tracheal aspirate was significantly associated with the
      presence of NETs and/or Cit-H3. The presence of bacteria in tracheal aspirate may
      be one important factor associated with NET formation. NETs may play a pivotal
      role in the biological defense against the dissemination of pathogens from the
      respiratory tract to the bloodstream in potentially infected patients. 

PMID- 25392952
TI  - Origins of marronage: Mitochondrial lineages of Jamaica's Accompong Town Maroons.
AB  - OBJECTIVES: The Accompong Town Maroons are descendants of enslaved Africans who
      successfully waged war against British colonial rule and established an
      independent community in western Jamaica. There are discrepancies regarding
      Accompong Town Maroon ancestry with some scholars noting ancestry from both
      Africans and Tainos, Jamaica's indigenous population, while other scholars only
      acknowledge African ancestry. We considered the mitochondrial lineages of
      contemporary Accompong Town Maroons to address the question of ancestral origins.
      METHODS: We sequenced a section of the mitochondrial DNA control region (np
      16,024-16,569) and genotyped a panel of hierarchically selected haplogroup
      diagnostic SNPs for 50 individuals with genealogical ties to Accompong Town.
      Mitochondrial haplotypes were also compared with publically available Jamaican
      mitochondrial haplotypes using an exact test as well as haplotypes within the
      EMPOP public database to further access biogeographic origins. RESULTS: L-type
      mitochondrial haplogroups were observed in 96% of samples, and the remaining 4%
      belonged to haplogroup B2. Haplotype diversity was 0.922 (SD = 0.024) and not
      significantly different than the comparable Jamaican population. Of the two B2
      haplotypes, one matched haplotypes throughout the Americas and East Asia and the
      other matched only in East Asia. These results suggest both African and
      indigenous American maternal ancestries within Accompong Town. CONCLUSIONS: Our
      data suggested that the maternal ancestry of contemporary Accompong Town Maroons
      is predominantly African and, despite claims to suggest otherwise, also
      indigenous American. Our study complemented Maroon oral histories, archeological
      data, and illuminated how colonization shaped human genetic variation within the
      Caribbean.

PMID- 25392953
TI  - Polymorphism of LRP5 gene and emphysema severity are associated with osteoporosis
      in Japanese patients with or at risk for COPD.
AB  - BACKGROUND AND OBJECTIVE: Osteoporosis is an important systemic comorbidity of
      chronic obstructive pulmonary disease (COPD). However, neither its mechanisms nor
      its risk factors have been fully elucidated. With regard to genetic factors, low
      density lipoprotein receptor-related protein 5 (LRP5) A1330V is known to be
      associated with osteoporosis in the general population, but the influence of this
      polymorphism in COPD is unknown. The aim of this study was to investigate the
      potential risk factors of COPD-related bone loss and fracture. METHODS: Keio
      University and affiliated hospitals have enrolled an observational cohort to
      investigate the management of COPD comorbidities. To assess risk factors for
      osteopenia and osteoporosis, bone mineral density (BMD) of the hip and lumbar
      spine, presence of vertebral fracture, quantitative data on emphysema and airway
      wall on computed tomography, as well as LRP5 genotype were analysed in patients
      with or at risk for COPD (n = 270). RESULTS: The percentage of subjects with
      osteoporosis (T-score <= -2.5), osteopenia (T-score between -1 and -2.5) and a
      normal BMD (T-score >= -1) was 15.2%, 35.9% and 48.9%, respectively. T-score was
      significantly decreased in subjects with LRP5 TT genotype (n = 15) compared with
      that in those with CC/CT genotype (n = 255) (-1.83 vs. -0.98, P = 0.0167). On
      multivariate logistic regression analysis, female gender (odds ratio (OR) 10.4; P
      < 0.0001), severe emphysema (OR 2.3; P = 0.013) and LRP5 TT genotype (OR 3.7; P =
      0.031) independently increased the risk of osteopenia/osteoporosis. CONCLUSIONS:
      This study confirmed the complex pathophysiology of COPD-related osteoporosis,
      including the influence of gender, clinical phenotype and genetic factors.

PMID- 25392954
TI  - Exhaled air dispersion during noninvasive ventilation via helmets and a total
      facemask.
AB  - BACKGROUND: Noninvasive ventilation (NIV) via helmet or total facemask is an
      option for managing patients with respiratory infections in respiratory failure.
      However, the risk of nosocomial infection is unknown. METHODS: We examined
      exhaled air dispersion during NIV using a human patient simulator reclined at 45
      degrees  in a negative pressure room with 12 air changes/h by two different
      helmets via a ventilator and a total facemask via a bilevel positive airway
      pressure device. Exhaled air was marked by intrapulmonary smoke particles,
      illuminated by laser light sheet, and captured by a video camera for data
      analysis. Significant exposure was defined as where there was >= 20% of
      normalized smoke concentration. RESULTS: During NIV via a helmet with the
      simulator programmed in mild lung injury, exhaled air leaked through the neck
      helmet interface with a radial distance of 150 to 230 mm when inspiratory
      positive airway pressure was increased from 12 to 20 cm H2O, respectively, while
      keeping the expiratory pressure at 10 cm H2O. During NIV via a helmet with air
      cushion around the neck, there was negligible air leakage. During NIV via a total
      facemask for mild lung injury, air leaked through the exhalation port to 618 and
      812 mm when inspiratory pressure was increased from 10 to 18 cm H2O,
      respectively, with the expiratory pressure at 5 cm H2O. CONCLUSIONS: A helmet
      with a good seal around the neck is needed to prevent nosocomial infection during
      NIV for patients with respiratory infections.

PMID- 25392951
TI  - Fluconazole alters the polysaccharide capsule of Cryptococcus gattii and leads to
      distinct behaviors in murine Cryptococcosis.
AB  - Cryptococcus gattii is an emergent human pathogen. Fluconazole is commonly used
      for treatment of cryptococcosis, but the emergence of less susceptible strains to
      this azole is a global problem and also the data regarding fluconazole-resistant
      cryptococcosis are scarce. We evaluate the influence of fluconazole on murine
      cryptococcosis and whether this azole alters the polysaccharide (PS) from
      cryptococcal cells. L27/01 strain of C. gattii was cultivated in high fluconazole
      concentrations and developed decreased drug susceptibility. This phenotype was
      named L27/01F, that was less virulent than L27/01 in mice. The physical,
      structural and electrophoretic properties of the PS capsule of L27/01F were
      altered by fluconazole. L27/01F presented lower antiphagocytic properties and
      reduced survival inside macrophages. The L27/01F did not affect the central
      nervous system, while the effect in brain caused by L27/01 strain began after
      only 12 hours. Mice infected with L27/01F presented lower production of the pro
      inflammatory cytokines, with increased cellular recruitment in the lungs and
      severe pulmonary disease. The behavioral alterations were affected by L27/01, but
      no effects were detected after infection with L27/01F. Our results suggest that
      stress to fluconazole alters the capsule of C. gattii and influences the clinical
      manifestations of cryptococcosis. 

PMID- 25392955
TI  - Editorial comment to Infectious aortic aneurysms occurring 1 year after bacillus
      Calmette-Guerin bladder instillation therapy.

PMID- 25392956
TI  - A novel tyrosine-heme C-O covalent linkage in F43Y myoglobin: a new post
      translational modification of heme proteins.
AB  - Heme post-translational modification plays a key role in tuning the structure and
      function of heme proteins. We herein report a novel tyrosine-heme covalent C-O
      bond in an artificially produced sperm whale myoglobin (Mb) mutant, F43Y Mb,
      which formed spontaneously in vivo between the Tyr43 hydroxy group and the heme 4
      vinyl group. This highlights the diverse chemistry of heme post-translational
      modifications, and lays groundwork for further investigation of the structural
      and functional diversity of covalently-bound heme proteins.

PMID- 25392957
TI  - Cluster harvesting in the WBr6-P system.
AB  - A combined thermal scanning-X-ray diffraction (XRD) approach was performed for
      the WBr(6)-P system to detect and analyze phases in this system, including metal
      rich phases generated with increasing amounts of elemental (red) phosphorus under
      partial PBr(3) release. Phases were characterized by powder XRD. A black
      crystalline powder of W(4)(PBr)Br(10) was obtained after reduction of WBr(6) with
      elemental phosphorus at 450  degrees C. The crystal structure of the new compound
      was found to be isotypic with the structure of W(4)(PCl)Cl(10) on the basis of
      powder XRD data. The structure of W(4)(PBr)Br(10) is represented by a
      cyclobutadiene-like tetranuclear tungsten cluster interconnected into a layered
      (W(4)(MU(4)-PBr)Br(6)(i))Br(8)/(2)(a-a) arrangement via outer bromide ligands.
      The MU(4)-capping bromophosphinidene ligand was verified by solid-state magic
      angle spinning (31)P NMR spectroscopy.

PMID- 25392958
TI  - Treatment of alcohol dependence: recent progress and reduction of consumption.
AB  - Alcohol dependence (AD) is a major public health problem. Currently, three drugs
      for the treatment of AD have been approved by both the European Medicines Agency
      (EMA) and the Food and Drug Administration (FDA): acamprosate, disulfiram, and
      oral naltrexone. The FDA also approved the use of long-acting injectable
      naltrexone. In Austria and in Italy sodium oxybate is also approved. The EMA's
      Committee for Medicinal Products for Human Use has recently granted marketing
      authorization for nalmefene for the reduction of alcohol consumption. Many
      patients, while accepting the problem, are unable or unwilling to completely stop
      consuming alcohol, leading to an inevitable deterioration over time of their
      psycho-physical state, and social and family relationships. It is appropriate to
      offer these patients the opportunity to significantly reduce their consumption of
      alcohol. The reduction may be an opportunity to prepare the individual for
      achieving complete abstinence. Abstinence should always be the main goal.
      Currently, nalmefene is the only drug that has been authorized for the reduction
      of alcohol consumption. Its association with psycho-social support is mandatory;
      it is taken on an "as-needed" basis, which should preferably be 1-2 hours before
      the possible intake of alcohol. The trials showed a significant reduction in
      alcohol consumption, which resulted in a significant reduction in morbidity and
      mortality. Reducing consumption allows a decrease in the progression of numerous
      alcohol-induced chronic diseases, as well as a reduction in psycho-physical
      damage, acts of violence, motor vehicle accidents, and accidents at work, which
      in turn means fewer healthcare costs. 

PMID- 25392959
TI  - [Paracetamol-codeine, an always actual choice for the treatment of pain].
AB  - Acute pain of mild to moderate intensity is one of the problems most frequently
      encountered in primary care and emergency medicine and is a major reason of
      request for visit by patients. In recent years the focus has been more on the
      treatment of chronic pain, perhaps ignoring the negative impact of acute pain on
      quality of life and functional status of the patient, despite a growing number of
      evidence indicating the need to treat optimally also acute pain to avoid it
      prolongs in time. The remarkable progress achieved in the understanding of the
      physiological mechanisms of the nociceptive stimulus, as well as those common to
      biochemical inflammation and acute pain, highlighted the active and complex role
      of central nervous system in the genesis and maintenance of pain that from acute,
      if not promptly and adequately treated, can become chronic. In this article,
      after a brief introduction on the most recent advances on the transition from
      acute to chronic pain, we have focused on paracetamol, an analgesic drug widely
      used for over a century for its demonstrated efficacy and tolerability.
      Paracetamol that, thanks to a complex and not yet fully defined mechanism of
      action, certainly localized in the central nervous system, can have a significant
      role in the early treatment of acute pain aimed to reduce the risk of
      chronicization. Pharmacokinetic parameters and pharmacodynamic studies are
      outlined, as well as the latest acquisitions in terms of metabolism of this drug
      and the risks related to its misuse. Are also discussed the recommendations
      issued by scientific societies and recent articles that indicate paracetamol as
      the drug of first choice for mild to moderate pain in various clinical settings,
      such as post-operative pain, post-traumatic and osteoarticular diseases, alone or
      in association with weak opioids, in particular with codeine. Most recent
      findings about metabolism and analgesic effect of codeine and its metabolites are
      highlighted, and how, in combination with acetaminophen, there is an increase in
      analgesic efficacy without increasing side effects, offering the chance of
      obtaining a better pain control. 

PMID- 25392960
TI  - [Topical pharmacologic approach with 5% lidocaine medicated plaster in the
      treatment of localized neuropathic pain].
AB  - The treatment of neuropathic pain is a medical challenge. The responsiveness to
      the different classes of drugs is often unsatisfactory and frequently associated
      to a wide range of side effects. International guidelines suggest for the
      "localized" neuropathic pain the topical treatment with 5% lidocaine medicated
      plaster, alone or associated to systemic drugs, as the first choice since its
      favorable efficacy and tolerability profile. Many clinical experiences support
      the rationale for using 5% lidocaine medicated plaster in different kinds of
      localized neuropathic pain, such as postherpetic and trigeminal neuralgia,
      compressive syndromes, painful diabetic polyneuropathy and pain secondary to
      trauma or surgical interventions. This paper reports a series of clinical cases
      whose heterogeneity suggests the wide burden of applicability of the topical 5%
      lidocaine, either alone and associated to systemic drugs. All the described
      conditions were characterized by a highly intense pain, not adequately controlled
      by actual medications, which improved after the use of topical lidocaine. The
      good response to lidocaine allowed the reduction, of even the withdrawal, of
      concurrent drugs and improved the patients' quality of life. 

PMID- 25392961
TI  - The brown coat colour of Coppernecked goats is associated with a non-synonymous
      variant at the TYRP1 locus on chromosome 8.
AB  - The recent development of a goat SNP genotyping microarray enables genome-wide
      association studies in this important livestock species. We investigated the
      genetic basis of the black and brown coat colour in Valais Blacknecked and
      Coppernecked goats. A genome-wide association analysis using goat SNP50 BeadChip
      genotypes of 22 cases and 23 controls allowed us to map the locus for the brown
      coat colour to goat chromosome 8. The TYRP1 gene is located within the associated
      chromosomal region, and TYRP1 variants cause similar coat colour phenotypes in
      different species. We thus considered TYRP1 as a strong positional and functional
      candidate. We resequenced the caprine TYRP1 gene by Sanger and Illumina
      sequencing and identified two non-synonymous variants, p.Ile478Thr and
      p.Gly496Asp, that might have a functional impact on the TYRP1 protein. However,
      based on the obtained pedigree and genotype data, the brown coat colour in these
      goats is not due to a single recessive loss-of-function allele. Surprisingly, the
      genotype distribution and the pedigree data suggest that the (496) Asp allele
      might possibly act in a dominant manner. The (496) Asp allele was present in 77
      of 81 investigated Coppernecked goats and did not occur in black goats. This
      strongly suggests heterogeneity underlying the brown coat colour in Coppernecked
      goats. Functional experiments or targeted matings will be required to verify the
      unexpected preliminary findings. 

PMID- 25392965
TI  - Acute postoperative visual loss.

PMID- 25392966
TI  - Sudden-onset paracentral vision loss.

PMID- 25392967
TI  - Increased forest carbon storage with increased atmospheric CO2 despite nitrogen
      limitation: a game-theoretic allocation model for trees in competition for
      nitrogen and light.
AB  - Changes in resource availability often cause competitively driven changes in tree
      allocation to foliage, wood, and fine roots, either via plastic changes within
      individuals or through turnover of individuals with differing strategies. Here,
      we investigate how optimally competitive tree allocation should change in
      response to elevated atmospheric CO2 along a gradient of nitrogen and light
      availability, together with how those changes should affect carbon storage in
      living biomass. We present a physiologically-based forest model that includes the
      primary functions of wood and nitrogen. From a tree's perspective, wood is an
      offensive and defensive weapon used against neighbors in competition for light.
      From a biogeochemical perspective, wood is the primary living reservoir of stored
      carbon. Nitrogen constitutes a tree's photosynthetic machinery and the support
      systems for that machinery, and its limited availability thus reduces a tree's
      ability to fix carbon. This model has been previously successful in predicting
      allocation to foliage, wood, and fine roots along natural productivity gradients.
      Using game theory, we solve the model for competitively optimal foliage, wood,
      and fine root allocation strategies for trees in competition for nitrogen and
      light as a function of CO2 and nitrogen mineralization rate. Instead of down
      regulating under nitrogen limitation, carbon storage under elevated CO2 relative
      to carbon storage at ambient CO2 is approximately independent of the nitrogen
      mineralization rate. This surprising prediction is a consequence of both
      increased competition for nitrogen driving increased fine root biomass and
      increased competition for light driving increased allocation to wood under
      elevated CO2 . 

PMID- 25392968
TI  - Neural injury markers to predict neonatal complications in intrauterine growth
      restriction.
AB  - We assessed the neural injury markers (NIMs) in maternal and umbilical blood in
      preterm deliveries with and without intrauterine growth restriction (IUGR), and
      relationship between NIMs and neonatal complications. Deliveries between 24 and
      34 weeks' gestation with (study group) and without (control group) IUGR were
      included to the study. Three NIMs (s100B, neurone-specific enolase [NSE] and
      alpha-foetoprotein [AFP]) were investigated in umbilical arterial, umbilical
      venous and maternal venous serum. Thirty-two IUGR and twenty-nine non-IUGR
      pregnancies with preterm delivery were included. Maternal and umbilical arterial
      s100B levels were significantly higher in the study group, whereas there was no
      relationship among IUGR, AFP and NSE levels. In the study group, umbilical venous
      s100B and NSE levels were associated with perinatal mortality (p = 0.012, 0.005,
      respectively), necrotising enterocolitis (NEC) (p = 0.001, 0.04, respectively)
      and need for intubation (p = 0.001, 0.007, respectively). Negative predictive
      values for perinatal mortality and NEC were 100% and for need for intubation it
      was 92.8% when both s100B and NSE were below the cutoff line determined by the
      receiver-operating characteristic curves. Perinatal mortality, NEC and need for
      intubation can be predicted by assessment of umbilical venous s100B and NSE
      measurement during birth in IUGR newborns. 

PMID- 25392970
TI  - Great auricular nerve preservation in parotid gland surgery: Long-term outcomes.
AB  - OBJECTIVES/HYPOTHESIS: To assess sensory outcomes and quality of life (QoL) in
      two groups of patients with and without great auricular nerve (GAN) preservation
      during parotidectomy. STUDY DESIGN: Retrospective chart review. METHODS: The
      posterior branch of the GAN was preserved in 42 patients (group A) and sacrificed
      in 13 (group B). Tactile, heat, and cold sensitivities were investigated by
      dividing GAN territory into seven areas. Comparisons between operated (OS) and
      nonoperated sides (NS) within each group, and between the OS of the two groups
      were made. The QoL questionnaire was administered. RESULTS: In group A, normal
      tactile, heat, and cold sensitivities ranged from 16.7% to 66.7%, 11.9% to 73.8%,
      and 21.4% to 81%, respectively, in different OS areas. Significant differences
      between OS and NS were found, except for the preauricular superior area. In group
      B, normal tactile, heat, and cold sensitivities ranged from 0% to 61.5%, 0% to
      53.8%, and 7.7% to 76.9%, respectively, in different OS areas. Significant
      differences between OS and NS were found except for the preauricular superior
      (tactile sensitivity), and preauricular superior and helix/concha areas (cold
      sensitivity). Comparing the OS tactile and thermic sensitivities between the two
      groups, only the lobule area showed differences. The preauricular inferior area
      was different only for heat. The QoL questionnaire showed different hypoesthesia
      extension between the two groups. All other items were comparable. CONCLUSIONS:
      Sensory deficits are commonly reported despite GAN preservation. Lobule and
      preauricular inferior areas showed differences in terms of tactile and thermic
      sensitivities, with better outcomes in group A. QoL seems tolerable despite GAN
      sacrifice. LEVEL OF EVIDENCE: 4

PMID- 25392969
TI  - Predictive factors of stress incontinence after posterior sacral rhizotomy.
AB  - AIMS: The Brindley procedure, used since the 1980s, consists of implantation of a
      stimulator for sacral anterior root stimulation combined with a posterior sacral
      rhizotomy to enable micturition. Patients suitable for the procedure are patients
      with detrusor overactivity and a complete spinal cord lesion with intact sacral
      reflexes. S2 to S4 posterior sacral rhizotomy abolishes sacral hyperreflexia and
      may lead to decreased urethral closure pressure and loss of reflex adaptation of
      continence, leading to stress incontinence. METHODS: In this retrospective study
      of 96 patients from Nantes or Le Mans, implanted with a Finetech-Brindley
      stimulator, we analyzed the incidence of stress incontinence one year after
      surgery and looked for predictive factors of stress incontinence one year after
      posterior sacral rhizotomy: age, gender, level of injury between T10 and L2 ,
      previous urethral surgery, incompetent bladder neck, Maximum Urethral Closure
      Pressure before surgery less than 30 cmH2 O, compliance before surgery less than
      30 ml/cmH2 0. Patients with persistent involuntary detrusor contractions with or
      without incontinence after surgery were excluded. RESULTS: One year after
      surgery, 10.4% of the patients experienced stress incontinence. Urethral closure
      pressure was significantly decreased by 18% after posterior sacral rhizotomy (P =
      0.002). This study highlights the only significant predictive factor of stress
      incontinence after rhizotomy: incompetent bladder neck (P = 0.002). CONCLUSIONS:
      As screening of patients undergoing the Brindley procedure is essential to
      achieve optimal postoperative results, on the basis of this study, we propose
      preoperative assessment to select the population of patients most likely to
      benefit from the Brindley procedure.

PMID- 25392971
TI  - Morphological alterations of periodontal pocket epithelium following Nd:YAG laser
      irradiation.
AB  - OBJECTIVE: The purpose of this in vivo study was to examine morphologic
      alterations in the periodontal pocket epithelium with presence or absence of
      clinical inflammation following the use of the Neodymium: Yttrium-Aluminum-Garnet
      (Nd:YAG) laser irradiation. BACKGROUND DATA: Subgingival Nd:YAG laser irradiation
      has been proposed as an alternative technique for treatment of chronic
      periodontitis. Several published studies have reported the clinical outcomes of
      such treatment. METHODS: Twenty patients, diagnosed with moderate chronic
      periodontitis, were selected for the study. A total of 32 sites was identified
      and divided into a control (n=18) and laser-treated test groups (n=14). Probing
      depth (PD) and bleeding on probing (BOP) were recorded for all sites. Test sites
      were irradiated with an Nd:YAG laser using parameters of 2 W, 200 mJ pulse
      energy, and 10 pps delivered through a 320 MUm diameter tip. Total laser
      treatment time ranged from 1 to 2 min. Following treatment, all specimens were
      harvested via biopsy and processed for scanning electron microscopy (SEM) and
      histologic examination. RESULTS: Control group specimens, depending upon initial
      PD, exhibited either a relatively smooth and intact epithelium with little
      desquamation (PD<=3 mm), or increasing degrees of epithelial desquamation and
      leukocytic infiltration at a PD of >=4 mm. In the laser-treated test group, the
      specimens with PD<=3 mm that were BOP negative (-) exhibited a thin layer of
      epithelium that was disrupted. In the specimens with initial PD of >=4 mm,
      complete removal of the epithelium whose extent and degree were increasing, was
      observed in the inflamed portion, while epithelium remained in the uninflamed
      portion. CONCLUSIONS: The SEM and histologic findings demonstrated the
      feasibility of ablating pocket epithelium with an Nd:YAG laser irradiation using
      parameters of 2 W of power (200 mJ, 10 pps). Furthermore, the presence or absence
      of clinical inflammation appeared to have an impact on the degree of laser
      mediated epithelial ablation.

PMID- 25392972
TI  - Endoscopic ultrasound-guided gallbladder drainage for the management of acute
      cholecystitis (with video).
AB  - Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been introduced
      as an alternative to percutaneous transhepatic gallbladder drainage for the
      treatment of acute cholecystitis in non-surgical candidates. A systematic review
      of the English language literature through PubMed search until June 2014 was
      conducted. One hundred and fifty-five patients with acute cholecystitis treated
      with EUS-GBD in eight studies and 12 case reports, and two patients with EUS-GBD
      for other causes were identified. Overall, technical success was obtained in 153
      patients (97.45%) and clinical success in 150 (99.34%) patients with acute
      cholecystitis. Adverse events developed in less than 8% of patients, all of them
      managed conservatively. EUS-GBD has been performed with plastic stents,
      nasobiliary drainage tubes, standard or modified tubular self-expandable metal
      stents (SEMS) and lumen-apposing metal stents (LAMS) by different authors with
      apparently similar outcomes. No comparison studies between stent types for EUS
      GBD have been reported. EUS-GBD is a promising novel alternative intervention for
      the treatment of acute cholecystitis in high surgical risk patients. Feasibility,
      safety and efficacy in published studies from expert centers are very high
      compared to currently available alternatives. Further studies are needed to
      establish the safety and long-term outcomes of this procedure in other practice
      settings before EUS-GBD can be widely disseminated. 

PMID- 25392973
TI  - Determination of multiple phytohormones in fruits by high-performance liquid
      chromatography with fluorescence detection using dispersive liquid-liquid
      microextraction followed by precolumn fluorescent labeling.
AB  - Plant hormone determination in food matrices has attracted more and more
      attention because of their potential risks to human health. However, analytical
      methods for the analysis of multiple plant hormones remain poorly investigated.
      In the present study, a convenient, selective, and ultrasensitive high
      performance liquid chromatography method for the simultaneous determination of
      multiple classes of plant hormones has been developed successfully using
      dispersive liquid-liquid microextraction followed by precolumn fluorescent
      labeling. Eight plant hormones in fruits including jasmonic acid, 12-oxo
      phytodienoic acid, indole-3-acetic acid, 3-indolybutyric acid, 3-indolepropionic
      acid, gibberellin A3 , 1-naphthylacetic acid, and 2-naphthaleneacetic acid were
      analyzed by this method. The conditions employed for dispersive liquid-liquid
      microextraction were optimized systematically. The linearity for all plant
      hormones was found to be >0.9993 (R(2) values). This method offered low detection
      limits of 0.19-0.44 ng/mL (at a signal-to-noise ratio of 3), and method
      accuracies were in the range of 92.32-103.10%. The proposed method was applied to
      determine plant hormones in five kinds of food samples, and this method can
      achieve a short analysis time, low threshold levels of detection, and a high
      specificity for the analysis of targeted plant hormones present at trace level
      concentrations in complex matrices. 

PMID- 25392974
TI  - Decadelong profile of women in ophthalmic publications.
AB  - IMPORTANCE: In recent decades, there has been an increase in the number of women
      practicing medicine. We believe this shift may be reaching academic publications
      in ophthalmology and changing gender trends. OBJECTIVE: To determine whether
      there has been an increase in women publishing academic articles and editorials
      in ophthalmology during the past decade. DESIGN, SETTING, AND PARTICIPANTS: In
      this observational retrospective study, 3 ophthalmology journals were sampled
      from 2000 and 2010 for at least 100 articles per journal, per year, and all
      editorials published in both years. Data reviewed included the authors' gender,
      number of authors, number of references, subspecialty, and country of origin.
      EXPOSURE: Publication by women authors. MAIN OUTCOMES AND MEASURES: The primary
      outcome measure was an increase in women publishing in ophthalmology. The
      hypothesis was formulated before data collection. RESULTS: Our analysis included
      671 original articles (336 from 2000 and 335 from 2010) and 89 editorials. The
      percentage of original articles with a woman as first author increased from 23.2%
      in 2000 to 32.5% in 2010, a difference of 9.3% (95% CI, 23.3%-32.5%; P = .005).
      The percentage of original articles with a woman last author increased from 16.4%
      in 2000 to 24.2% in 2010, a difference of 7.8% (95% CI, 16.4%-24.2%; P = .01).
      The percentage of original articles with a woman first author increased in Asia
      from 1.2% in 2000 to 8.4% in 2010, a difference of 7.2% (95% CI, 1.2%-8.4%; P <
      .001). The percentage of articles with a woman last author increased in Europe
      from 2.2% in 2000 to 7.5% in 2010, a difference of 5.3% (95% CI, 2.2%-7.5%; P <
      .001) and in Asia from 0% in 2000 to 6.0% in 2010, a difference of 6.0% (95% CI,
      0%-6%; P < .001). Editorials were written predominantly by men: 33 of 38
      editorials (87%) in 2000 and 46 of 51 (90%) in 2010, a difference of 3% (95% CI,
      87%-90%; P = .62), showing a trend toward decreased editorial authorship by women
      during the past decade. CONCLUSIONS AND RELEVANCE: Our data suggest an increase
      in women publishing original investigations in ophthalmic literature, but no
      increase in editorial authorship.

PMID- 25392975
TI  - Linear-scaling self-consistent field calculations based on divide-and-conquer
      method using resolution-of-identity approximation on graphical processing units.
AB  - Graphical processing units (GPUs) are emerging in computational chemistry to
      include Hartree-Fock (HF) methods and electron-correlation theories. However, ab
      initio calculations of large molecules face technical difficulties such as slow
      memory access between central processing unit and GPU and other shortfalls of GPU
      memory. The divide-and-conquer (DC) method, which is a linear-scaling scheme that
      divides a total system into several fragments, could avoid these bottlenecks by
      separately solving local equations in individual fragments. In addition, the
      resolution-of-the-identity (RI) approximation enables an effective reduction in
      computational cost with respect to the GPU memory. The present study implemented
      the DC-RI-HF code on GPUs using math libraries, which guarantee compatibility
      with future development of the GPU architecture. Numerical applications confirmed
      that the present code using GPUs significantly accelerated the HF calculations
      while maintaining accuracy.

PMID- 25392976
TI  - Discussion: Financial conflicts of interests in plastic surgery: background,
      potential for bias, disclosure, and transparency.

PMID- 25392977
TI  - Discussion: Financial conflicts of interest in plastic surgery: background,
      potential for bias, disclosure, and transparency.

PMID- 25392978
TI  - Pitfalls in imaging the frail elderly.
AB  - The number of older people in the UK is rising and will continue to increase.
      Furthermore, there is evidence that (i) the number of investigations on the
      oldest patients is disproportionately increasing, (ii) inappropriate and/or
      futile radiological investigations are commonplace and (iii) the requests are
      coming from the most junior doctors. In this article, we argue that the approach
      to investigating the frail elderly is different and complex. Careful thought and
      discussion is necessary to safely and compassionately investigate treatable
      conditions without causing unnecessary distress and suffering. 

PMID- 25392979
TI  - In vivo proton MR spectroscopy of pancreatic neuroendocrine tumors in a multiple
      endocrine neoplasia type 1 conditional knockout mouse model.
AB  - PURPOSE: MR spectroscopy (MRS) can improve diagnosis and follow treatment in
      cancer. However, no study has yet reported application of in vivo (1)H-MRS in
      malignant pancreatic lesions. This study quantitatively determined whether in
      vivo (1)H-MRS on multiple endocrine neoplasia type 1 (Men1) conditional knockout
      (KO) mice and their wild type (WT) littermates could detect differences in total
      choline (tCho) levels between tumor and control pancreas. METHODS: Relative tCho
      levels in pancreatic tumors or pancreata from KO and WT mice were determined
      using in vivo (1)H-MRS at 9.4 T. The levels of Cho-containing compounds were also
      quantified using in vitro (1)H-NMR on extracts of pancreatic tissues from KO and
      WT mice, respectively, and on extracts of pancreatic tissues from patients with
      pancreatic neuroendocrine tumors (PNETs). RESULTS: tCho levels measured by in
      vivo (1)H-MRS were significantly higher in PNETs from KO mice compared to the
      normal pancreas from WT mice. The elevated choline-containing compounds were also
      identified in pancreatic tumors from KO mice and tissues from patients with PNETs
      via in vitro (1)H-NMR. CONCLUSION: These results indicate the potential use of
      tCho levels estimated via in vivo (1)H-MRS in differentiating malignant
      pancreatic tumors from benign tumors.

PMID- 25392980
TI  - Dedicated paediatric teaching remains critical to the undergraduate medical
      curriculum.

PMID- 25392981
TI  - Software-based evaluation of human age: a pilot study.
AB  - PURPOSE: This pilot study was to assess a smartphone application regarding its
      use as an objective evaluation tool for subject age in comparison to human raters
      and to identify potential factors influencing the estimation of age. MATERIALS
      AND METHODS: Ten Caucasian participants (six females, four males, mean age 42.1
      +/- 22.6 years) were randomly chosen, and frontal facial pictures of each
      participant were taken. The smartphone application PhotoAge (Version 1.5,
      (c)2012, Percipo Inc., San Francisco, CA, USA) was used to evaluate the age of
      the participants. For comparison, 100 randomly selected raters (60 females, 40
      males, mean age 29.3 +/- 1.3 years) were asked to evaluate the age of the same
      participants. The influence of participants' facial expression, age, and sex as
      well as raters' age, sex, and profession was investigated as well. Statistical
      analyses (linear mixed models with random intercepts; least square means,
      confidence interval 95%; p < 0.05) were implemented. RESULTS: PhotoAge resulted
      in a mean age of 43.1 +/- 18.2 years, with a difference from the true mean age of
      1.0 +/- 8.2 years (p = 0.5996). The evaluation by the raters revealed a mean age
      of 41.5 +/- 19.0 years, with a difference from the true mean age of -0.6 +/- 8.5
      years (p = 0.6078). There was no statistical significance between the two groups
      (p = 0.2783). CONCLUSION: The evaluation of age with the software application
      PhotoAge seems to be a reliable procedure with comparable results to human
      raters. CLINICAL SIGNIFICANCE: This study gives a better understanding about the
      reliability of a software-based evaluation tool for age and identifies factors
      (e.g., the visibility of the teeth) potentially affecting the estimation of age.
      Naturally looking teeth seem to have no influence on the evaluation of a person's
      age. Thus, the application of this specific application for dental purposes is
      questionable; however, in forensics, it might be a valuable tool for estimating a
      person's age.

PMID- 25392982
TI  - SAD effects on grantsmanship.
AB  - SAD is a state of depression induced by a lack of sufficient sunlight that occurs
      at high latitudes during the fall and winter. SAD causes people to be risk
      adverse. Granting agencies of high latitude countries should time high-risk
      research competitions so they do not coincide with the SAD months. 

PMID- 25392984
TI  - Oxidation potentials of N-modified derivatives of the analgesic flupirtine linked
      to potassium KV 7 channel opening activity but not hepatocyte toxicity.
AB  - Openers of neuronal voltage-gated potassium channels (KV ) are of interest as
      therapeutic agents for treating pain (flupirtine) and epilepsy (retigabine). In
      an effort to better understand the mechanisms of action and toxicity of
      flupirtine, we synthesized nine novel analogues with varying redox behavior.
      Flupirtine can be oxidatively metabolized into azaquinone diimines; thus, the
      oxidation potentials of flupirtine and its analogues were measured by cyclic
      voltammetry. KV 7.2/3 (KCNQ2/3) opening activity was determined by an established
      assay with HEK293 cells overexpressing these channels. A link was found between
      the oxidation potentials of the compounds and their EC50 values for potassium
      channel opening activity. On the other hand, no correlation was observed between
      oxidation potentials and cytotoxicity in cultures of transgenic mouse hepatocytes
      (TAMH). These results support the idea that oxidative metabolites of flupirtine
      contribute to the mechanism of action, similar to what was recently proposed for
      acetaminophen (paracetamol), but not to hepatotoxicity. 

PMID- 25392985
TI  - Development of a lexicon for caviar and its usefulness for determining consumer
      preference.
AB  - Although caviar is a premium product which offers nutritional benefits, few
      studies have characterized its sensory properties. As such, this study sought to
      develop a lexicon for sensory evaluation of caviar appearance, texture, aroma,
      and flavor/taste and to relate these attributes to consumer acceptance. A trained
      panel identified 16 sensory attributes for evaluation along a 15-cm scale and
      used CATA (check all that apply) methodology to indicate the less frequently
      encountered off-aromas, appearance traits, and persistent flavors. Using this
      lexicon, the trained panel described differences among caviar samples harvested
      from sturgeon fed varying diets. Acceptance of the caviar was also evaluated by a
      consumer panel. As evaluated by the trained panelists, analysis of variance
      (ANOVA) results indicated differences among caviar in the sensory attributes of
      tactile firmness, mustard color, egg size, in-mouth firmness, seafood fresh
      flavor, fresh butter flavor, earthy flavor, yeasty flavor, and bitterness (P <
      0.05). Logistic regression of CATA responses indicated that caviar varied by diet
      in several aroma and aftertaste attributes, and marbled appearance (P < 0.05).
      Using partial least squares analysis on the consumer and trained panel data,
      overall consumer acceptance of caviar was driven by tactile firmness, sea fresh
      flavor, fresh butter flavor, and black color. This overall acceptance was highly
      correlated with acceptance of texture (r = 0.867) and flavor/taste (r = 0.999).
      Overall, this lexicon allows for standardized sensory evaluation of caviar using
      a common set of descriptors. This lexicon and information regarding the drivers
      of caviar acceptance can be used by industry professionals to ensure optimal
      caviar quality. 

PMID- 25392983
TI  - Drep-2 is a novel synaptic protein important for learning and memory.
AB  - CIDE-N domains mediate interactions between the DNase Dff40/CAD and its inhibitor
      Dff45/ICAD. In this study, we report that the CIDE-N protein Drep-2 is a novel
      synaptic protein important for learning and behavioral adaptation. Drep-2 was
      found at synapses throughout the Drosophila brain and was strongly enriched at
      mushroom body input synapses. It was required within Kenyon cells for normal
      olfactory short- and intermediate-term memory. Drep-2 colocalized with
      metabotropic glutamate receptors (mGluRs). Chronic pharmacological stimulation of
      mGluRs compensated for drep-2 learning deficits, and drep-2 and mGluR learning
      phenotypes behaved non-additively, suggesting that Drep 2 might be involved in
      effective mGluR signaling. In fact, Drosophila fragile X protein mutants, shown
      to benefit from attenuation of mGluR signaling, profited from the elimination of
      drep-2. Thus, Drep-2 is a novel regulatory synaptic factor, probably intersecting
      with metabotropic signaling and translational regulation. 

PMID- 25392986
TI  - Protein-based functional nanomaterial design for bioengineering applications.
AB  - In this review article, we describe recent progress in the field of protein-based
      bionanomaterial design with focus on the four well-characterized proteins:
      mammalian elastin and collagen, and insect-derived silk and resilin. These
      proteins are important structural components and understanding their physical and
      biochemical properties has allowed us to not only replicate them but also create
      novel smart materials. The 'smart' properties of a material include its ability
      to self-assemble, respond to stimuli, and/or promote cell interactions. Such
      properties can be attributed to unique structural modules from elastin, collagen,
      silk, and resilin as well as functional modules identified from other proteins
      directly or using display techniques such as phage display. Thus, the goal of
      this article is to not only emphasize the types of protein-based peptide modules
      and their uses but also encourage and inspire the reader to create new toolsets
      of smart polypeptides to overcome their challenges.

PMID- 25392987
TI  - Uricosuric medications for chronic gout.
AB  - BACKGROUND: Uricosuric agents have long been used in the treatment of gout but
      there is little evidence regarding their benefit and safety in this condition.
      OBJECTIVES: To assess the benefits and harms of uricosuric medications in the
      treatment of chronic gout. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL, Issue 4, 2013), Ovid MEDLINE and Ovid
      EMBASE for studies to the 13 May 2013. We also searched the World Health
      Organization Clinical Trials Registry, ClinicalTrials.gov and the 2011 to 2012
      American College of Rheumatology and European League against Rheumatism
      abstracts. WE considered black box warnings and searched drug safety databases to
      identify and describe rare adverse events. SELECTION CRITERIA: We considered all
      randomised controlled trials (RCTs) or quasi-randomised controlled trials
      (controlled clinical trials (CCTs)) that compared uricosuric medications
      (benzbromarone, probenecid or sulphinpyrazone) alone or in combination with
      another therapy (placebo or other active uric acid-lowering medication, or non
      pharmacological treatment) in adults with chronic gout for inclusion. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected the studies
      for inclusion, extracted data and performed a risk of bias assessment. Main
      outcomes were frequency of acute gout attacks, serum urate normalisation, study
      participant withdrawal due to adverse events, total adverse events, pain
      reduction, function and tophus regression. MAIN RESULTS: The search identified
      four RCTs and one CCT that evaluated the benefit and safety of uricosurics for
      gout. One study (65 participants) compared benzbromarone with allopurinol for a
      duration of four months; one compared benzbromarone with allopurinol (36
      participants) for a duration of nine to 24 months; one study (62 participants)
      compared benzbromarone with probenecid for two months and one study (74
      participants) compared benzbromarone with probenecid. One study (37 participants)
      compared allopurinol with probenecid. No study was completely free from bias.Low
      quality evidence from one study (55 participants) comparing benzbromarone with
      allopurinol indicated uncertain effects in terms of frequency of acute gout
      attacks (4% with benzbromarone versus 0% with allopurinol; risk ratio (RR) 3.58,
      95% confidence interval (CI) 0.15 to 84.13), while moderate-quality evidence from
      two studies (101 participants; treated for four to nine months) indicated similar
      proportions of participants achieving serum urate normalisation (73.9% with
      benzbromarone versus 60% with allopurinol; pooled RR 1.27, 95% CI 0.90 to 1.79).
      Low-quality evidence indicated uncertain differences in withdrawals due to
      adverse events (7.1% with benzbromarone versus 6.1% with allopurinol; pooled RR
      1.25, 95% CI 0.28 to 5.62), and total adverse events (20% with benzbromarone
      versus 6.7% with allopurinol; RR 3.00, 95% CI 0.64 to 14.16). The study did not
      measure pain reduction, function and tophus regression.When comparing
      benzbromarone with probenecid, there was moderate-quality evidence based on one
      study (62 participants) that participants taking benzbromarone were more likely
      to achieve serum urate normalisation after two months (81.5% with benzbromarone
      versus 57.1% with probenecid; RR 1.43, 95% CI 1.02 to 2.00). This indicated that
      when compared with probenecid, five participants needed to be treated with
      benzbromarone in order to have one additional person achieve serum urate
      normalisation (number needed to treat for an additional beneficial outcome (NNTB)
      5). However, the second study reported no difference in the absolute decrease in
      serum urate between these groups after 12 weeks. Low-quality evidence from two
      studies (129 participants) indicated uncertain differences between treatments in
      the frequency of acute gout attacks (6.3% with benzbromarone versus 10.6% with
      probenecid; pooled RR 0.73, 95% CI 0.09 to 5.83); fewer withdrawals due to
      adverse events with benzbromarone (2% with benzbromarone versus 17% with
      probenecid; pooled RR 0.15, 95% CI 0.03 to 0.79, NNTB 7) and fewer total adverse
      events (21% with benzbromarone versus 47% with probenecid; pooled RR 0.43, 95% CI
      0.25 to 0.74; NNTB 4). The studies did not measure pain reduction, function and
      tophus regression.Low-quality evidence based on one small CCT (37 participants)
      indicated uncertainty around the difference in the incidence of acute gout
      attacks between probenecid and allopurinol after 18 to 20 months' treatment (53%
      with probenecid versus 55% with allopurinol; RR 0.96, 95% CI 0.53 to 1.75). The
      study did not measure or report the proportion achieving serum urate
      normalisation, pain reduction, function, tophus regression, withdrawal due to
      adverse events and total adverse events. AUTHORS' CONCLUSIONS: There was moderate
      quality evidence that there is probably no important difference between
      benzbromarone and allopurinol at achieving serum urate normalisation, but that
      benzbromarone is probably more successful than probenecid at achieving serum
      urate normalisation in people with gout. There is some uncertainty around the
      effect estimates, based on low-quality evidence from only one or two trials, on
      the number of acute gout attacks, the number of withdrawals due to adverse events
      or the total number of participants experiencing adverse events when comparing
      benzbromarone with allopurinol. However, when compared with probenecid,
      benzbromarone resulted in fewer withdrawals due to adverse events and fewer
      participants experiencing adverse events. Low-quality evidence from one small
      study indicated uncertain effects in the incidence of acute gout attacks when
      comparing probenecid with allopurinol therapy. We downgraded the evidence because
      of a possible risk of performance and other biases and imprecision.

PMID- 25392989
TI  - Observations of the "egg white injury" in ants.
AB  - A key determinant of the relationship between diet and longevity is the balance
      of protein to carbohydrate in the diet. Eating excess protein relative to
      carbohydrate shortens lifespan in solitary and social insects. Here we explored
      how lifespan and behavior in ants was affected by the quality of protein ingested
      and the presence of associated antinutrients (i.e. compounds that interfere with
      the absorption of nutrients). We tested diets prepared with either egg white
      protein only or a protein mixture. Egg white contains an anti-nutrient called
      avidin. Avidin binds to the B vitamin biotin, preventing its absorption. First,
      we demonstrate that an egg-white diet was twice as deleterious as a protein
      mixture diet. Second, we show that ingestion of egg-white diet drastically
      affected social behavior, triggering elevated levels of aggression within the
      colony. Lastly, we reveal that by adding biotin to the egg white diet we were
      able to lessen its detrimental effects. This latest result suggests that ants
      suffered biotin deficiency when fed the egg white diet. In conclusion, anti
      nutrients were known to affect health and performance of animals, but this is the
      first study showing that anti-nutrients also lead to severe changes in behavior. 

PMID- 25392990
TI  - Genetic analysis of a novel tubulin mutation that redirects synaptic vesicle
      targeting and causes neurite degeneration in C. elegans.
AB  - Neuronal cargos are differentially targeted to either axons or dendrites, and
      this polarized cargo targeting critically depends on the interaction between
      microtubules and molecular motors. From a forward mutagenesis screen, we
      identified a gain-of-function mutation in the C. elegans alpha-tubulin gene mec
      12 that triggered synaptic vesicle mistargeting, neurite swelling and
      neurodegeneration in the touch receptor neurons. This missense mutation replaced
      an absolutely conserved glycine in the H12 helix with glutamic acid, resulting in
      increased negative charges at the C-terminus of alpha-tubulin. Synaptic vesicle
      mistargeting in the mutant neurons was suppressed by reducing dynein function,
      suggesting that aberrantly high dynein activity mistargeted synaptic vesicles. We
      demonstrated that dynein showed preference towards binding mutant microtubules
      over wild-type in microtubule sedimentation assay. By contrast, neurite swelling
      and neurodegeneration were independent of dynein and could be ameliorated by
      genetic paralysis of the animal. This suggests that mutant microtubules render
      the neurons susceptible to recurrent mechanical stress induced by muscle
      activity, which is consistent with the observation that microtubule network was
      disorganized under electron microscopy. Our work provides insights into how
      microtubule-dynein interaction instructs synaptic vesicle targeting and the
      importance of microtubule in the maintenance of neuronal structures against
      constant mechanical stress. 

PMID- 25392991
TI  - Characterization of K-complexes and slow wave activity in a neural mass model.
AB  - NREM sleep is characterized by two hallmarks, namely K-complexes (KCs) during
      sleep stage N2 and cortical slow oscillations (SOs) during sleep stage N3. While
      the underlying dynamics on the neuronal level is well known and can be easily
      measured, the resulting behavior on the macroscopic population level remains
      unclear. On the basis of an extended neural mass model of the cortex, we suggest
      a new interpretation of the mechanisms responsible for the generation of KCs and
      SOs. As the cortex transitions from wake to deep sleep, in our model it
      approaches an oscillatory regime via a Hopf bifurcation. Importantly, there is a
      canard phenomenon arising from a homoclinic bifurcation, whose orbit determines
      the shape of large amplitude SOs. A KC corresponds to a single excursion along
      the homoclinic orbit, while SOs are noise-driven oscillations around a stable
      focus. The model generates both time series and spectra that strikingly resemble
      real electroencephalogram data and points out possible differences between the
      different stages of natural sleep. 

PMID- 25392992
TI  - Aminoterminal amphipathic alpha-helix AH1 of hepatitis C virus nonstructural
      protein 4B possesses a dual role in RNA replication and virus production.
AB  - Nonstructural protein 4B (NS4B) is a key organizer of hepatitis C virus (HCV)
      replication complex formation. In concert with other nonstructural proteins, it
      induces a specific membrane rearrangement, designated as membranous web, which
      serves as a scaffold for the HCV replicase. The N-terminal part of NS4B comprises
      a predicted and a structurally resolved amphipathic alpha-helix, designated as
      AH1 and AH2, respectively. Here, we report a detailed structure-function analysis
      of NS4B AH1. Circular dichroism and nuclear magnetic resonance structural
      analyses revealed that AH1 folds into an amphipathic alpha-helix extending from
      NS4B amino acid 4 to 32, with positively charged residues flanking the helix.
      These residues are conserved among hepaciviruses. Mutagenesis and selection of
      pseudorevertants revealed an important role of these residues in RNA replication
      by affecting the biogenesis of double-membrane vesicles making up the membranous
      web. Moreover, alanine substitution of conserved acidic residues on the
      hydrophilic side of the helix reduced infectivity without significantly affecting
      RNA replication, indicating that AH1 is also involved in virus production.
      Selective membrane permeabilization and immunofluorescence microscopy analyses of
      a functional replicon harboring an epitope tag between NS4B AH1 and AH2 revealed
      a dual membrane topology of the N-terminal part of NS4B during HCV RNA
      replication. Luminal translocation was unaffected by the mutations introduced
      into AH1, but was abrogated by mutations introduced into AH2. In conclusion, our
      study reports the three-dimensional structure of AH1 from HCV NS4B, and
      highlights the importance of positively charged amino acid residues flanking this
      amphipathic alpha-helix in membranous web formation and RNA replication. In
      addition, we demonstrate that AH1 possesses a dual role in RNA replication and
      virus production, potentially governed by different topologies of the N-terminal
      part of NS4B. 

PMID- 25392993
TI  - Atomistic detailed mechanism and weak cation-conducting activity of HIV-1 Vpu
      revealed by free energy calculations.
AB  - The viral protein U (Vpu) encoded by HIV-1 has been shown to assist in the
      detachment of virion particles from infected cells. Vpu forms cation-specific ion
      channels in host cells, and has been proposed as a potential drug target. An
      understanding of the mechanism of ion transport through Vpu is desirable, but
      remains limited because of the unavailability of an experimental structure of the
      channel. Using a structure of the pentameric form of Vpu--modeled and validated
      based on available experimental data--umbrella sampling molecular dynamics
      simulations (cumulative simulation time of more than 0.4 us) were employed to
      elucidate the energetics and the molecular mechanism of ion transport in Vpu.
      Free energy profiles corresponding to the permeation of Na+ and K+ were found to
      be similar to each other indicating lack of ion selection, consistent with
      previous experimental studies. The Ser23 residue is shown to enhance ion
      transport via two mechanisms: creating a weak binding site, and increasing the
      effective hydrophilic length of the channel, both of which have previously been
      hypothesized in experiments. A two-dimensional free energy landscape has been
      computed to model multiple ion permeation, based on which a mechanism for ion
      conduction is proposed. It is shown that only one ion can pass through the
      channel at a time. This, along with a stretch of hydrophobic residues in the
      transmembrane domain of Vpu, explains the slow kinetics of ion conduction. The
      results are consistent with previous conductance studies that showed Vpu to be a
      weakly conducting ion channel.

PMID- 25392994
TI  - Homozygosity mapping and whole exome sequencing reveal a novel homozygous COL18A1
      mutation causing Knobloch syndrome.
AB  - The aim of this study was to identify the genetic basis of a chorioretinal
      dystrophy with high myopia of unknown origin in a child of a consanguineous
      marriage. The proband and ten family members of Iranian ancestry participated in
      this study. Linkage analysis was carried out with DNA samples of the proband and
      her parents by using the Human SNP Array 6.0. Whole exome sequencing (WES) was
      performed with the patients' DNA. Specific sequence alterations within the
      homozygous regions identified by whole exome sequencing were verified by Sanger
      sequencing. Upon genetic analysis, a novel homozygous frameshift mutation was
      found in exon 42 of the COL18A1 gene in the patient. Both parents were
      heterozygous for this sequence variation. Mutations in COL18A1 are known to cause
      Knobloch syndrome (KS). Retrospective analysis of clinical records of the patient
      revealed surgical removal of a meningocele present at birth. The clinical
      features shown by our patient were typical of KS with the exception of
      chorioretinal degeneration which is a rare manifestation. This is the first case
      of KS reported in a family of Iranian ancestry. We identified a novel disease
      causing (deletion) mutation in the COL18A1 gene leading to a frameshift and
      premature stop codon in the last exon. The mutation was not present in SNP
      databases and was also not found in 192 control individuals. Its localization
      within the endostatin domain implicates a functional relevance of endostatin in
      KS. A combined approach of linkage analysis and WES led to a rapid identification
      of the disease-causing mutation even though the clinical description was not
      completely clear at the beginning. 

PMID- 25392995
TI  - Identification of a common non-apoptotic cell death mechanism in hereditary
      retinal degeneration.
AB  - Cell death in neurodegenerative diseases is often thought to be governed by
      apoptosis; however, an increasing body of evidence suggests the involvement of
      alternative cell death mechanisms in neuronal degeneration. We studied retinal
      neurodegeneration using 10 different animal models, covering all major groups of
      hereditary human blindness (rd1, rd2, rd10, Cngb1 KO, Rho KO, S334ter, P23H,
      Cnga3 KO, cpfl1, Rpe65 KO), by investigating metabolic processes relevant for
      different forms of cell death. We show that apoptosis plays only a minor role in
      the inherited forms of retinal neurodegeneration studied, where instead, a non
      apoptotic degenerative mechanism common to all mutants is of major importance.
      Hallmark features of this pathway are activation of histone deacetylase, poly-ADP
      ribose-polymerase, and calpain, as well as accumulation of cyclic guanosine
      monophosphate and poly-ADP-ribose. Our work thus demonstrates the prevalence of
      alternative cell death mechanisms in inherited retinal degeneration and provides
      a rational basis for the design of mutation-independent treatments. 

PMID- 25392996
TI  - Protein profiling of preeclampsia placental tissues.
AB  - Preeclampsia is a multi-system disorder involved in pregnancy without an
      effective treatment except delivery. The precise pathogenesis of this complicated
      disorder is still not completely understood. The objective of this study is to
      evaluate the alterations of protein expression and phosphorylations that are
      important in regulating placental cell function in preterm and term preeclampsia.
      Using the Protein Pathway Array, 38 proteins in placental tissues were found to
      be differentially expressed between preterm preeclampsia and gestational age
      matched control, while 25 proteins were found to be expressed differentially
      between term preeclampsia and matched controls. Among these proteins, 16 proteins
      and their associated signaling pathways overlapped between preterm and term
      preeclampsia, suggesting the common pathogenesis of two subsets of disease. On
      the other hand, many proteins are uniquely altered in either preterm or term
      preeclampsia and correlated with severity of clinical symptoms and outcomes,
      therefore, providing molecular basis for these two subsets of preeclampsia.
      Furthermore, the expression levels of some of these proteins correlated with
      neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt
      1) in women with preterm preeclampsia. These proteins could potentially be used
      as candidate biomarkers for predicting outcomes of preeclampsia. 

PMID- 25392997
TI  - TLR9 activation is triggered by the excess of stimulatory versus inhibitory
      motifs present in Trypanosomatidae DNA.
AB  - DNA sequences purified from distinct organisms, e.g. non vertebrate versus
      vertebrate ones, were shown to differ in their TLR9 signalling properties
      especially when either mouse bone marrow-derived- or human dendritic cells (DCs)
      are probed as target cells. Here we found that the DC-targeting immunostimulatory
      property of Leishmania major DNA is shared by other Trypanosomatidae DNA,
      suggesting that this is a general trait of these eukaryotic single-celled
      parasites. We first documented, in vitro, that the low level of immunostimulatory
      activity by vertebrate DNA is not due to its limited access to DCs' TLR9. In
      addition, vertebrate DNA inhibits the activation induced by the parasite DNA.
      This inhibition could result from the presence of competing elements for TLR9
      activation and suggests that DNA from different species can be discriminated by
      mouse and human DCs. Second, using computational analysis of genomic DNA
      sequences, it was possible to detect the presence of over-represented inhibitory
      and under-represented stimulatory sequences in the vertebrate genomes, whereas L.
      major genome displays the opposite trend. Interestingly, this contrasting
      features between L. major and vertebrate genomes in the frequency of these motifs
      are shared by other Trypanosomatidae genomes (Trypanosoma cruzi, brucei and
      vivax). We also addressed the possibility that proteins expressed in DCs could
      interact with DNA and promote TLR9 activation. We found that TLR9 is specifically
      activated with L. major HMGB1-bound DNA and that HMGB1 preferentially binds to L.
      major compared to mouse DNA. Our results highlight that both DNA sequence and
      vertebrate DNA-binding proteins, such as the mouse HMGB1, allow the TLR9
      signaling to be initiated and achieved by Trypanosomatidae DNA. 

PMID- 25392998
TI  - Plasmodium falciparum transfected with ultra bright NanoLuc luciferase offers
      high sensitivity detection for the screening of growth and cellular trafficking
      inhibitors.
AB  - Drug discovery is a key part of malaria control and eradication strategies, and
      could benefit from sensitive and affordable assays to quantify parasite growth
      and to help identify the targets of potential anti-malarial compounds.
      Bioluminescence, achieved through expression of exogenous luciferases, is a
      powerful tool that has been applied in studies of several aspects of parasite
      biology and high throughput growth assays. We have expressed the new reporter
      NanoLuc (Nluc) luciferase in Plasmodium falciparum and showed it is at least 100
      times brighter than the commonly used firefly luciferase. Nluc brightness was
      explored as a means to achieve a growth assay with higher sensitivity and lower
      cost. In addition we attempted to develop other screening assays that may help
      interrogate libraries of inhibitory compounds for their mechanism of action. To
      this end parasites were engineered to express Nluc in the cytoplasm, the
      parasitophorous vacuole that surrounds the intraerythrocytic parasite or exported
      to the red blood cell cytosol. As proof-of-concept, these parasites were used to
      develop functional screening assays for quantifying the effects of Brefeldin A,
      an inhibitor of protein secretion, and Furosemide, an inhibitor of new permeation
      pathways used by parasites to acquire plasma nutrients. 

PMID- 25392999
TI  - Mimicking hypoxia to treat anemia: HIF-stabilizer BAY 85-3934 (Molidustat)
      stimulates erythropoietin production without hypertensive effects.
AB  - Oxygen sensing by hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) is the
      dominant regulatory mechanism of erythropoietin (EPO) expression. In chronic
      kidney disease (CKD), impaired EPO expression causes anemia, which can be treated
      by supplementation with recombinant human EPO (rhEPO). However, treatment can
      result in rhEPO levels greatly exceeding the normal physiological range for
      endogenous EPO, and there is evidence that this contributes to hypertension in
      patients with CKD. Mimicking hypoxia by inhibiting HIF-PHs, thereby stabilizing
      HIF, is a novel treatment concept for restoring endogenous EPO production. HIF
      stabilization by oral administration of the HIF-PH inhibitor BAY 85-3934
      (molidustat) resulted in dose-dependent production of EPO in healthy Wistar rats
      and cynomolgus monkeys. In repeat oral dosing of BAY 85-3934, hemoglobin levels
      were increased compared with animals that received vehicle, while endogenous EPO
      remained within the normal physiological range. BAY 85-3934 therapy was also
      effective in the treatment of renal anemia in rats with impaired kidney function
      and, unlike treatment with rhEPO, resulted in normalization of hypertensive blood
      pressure in a rat model of CKD. Notably, unlike treatment with the
      antihypertensive enalapril, the blood pressure normalization was achieved without
      a compensatory activation of the renin-angiotensin system. Thus, BAY 85-3934 may
      provide an approach to the treatment of anemia in patients with CKD, without the
      increased risk of adverse cardiovascular effects seen for patients treated with
      rhEPO. Clinical studies are ongoing to investigate the effects of BAY 85-3934
      therapy in patients with renal anemia. 

PMID- 25393000
TI  - Normal and functional TP53 in genetically stable myxoid/round cell liposarcoma.
AB  - Myxoid/round-cell liposarcoma (MLS/RCLS) is characterized by either the fusion
      gene FUS-DDIT3 or the less commonly occurring EWSR1-DDIT3 and most cases carry
      few or no additional cytogenetic changes. There are conflicting reports
      concerning the status and role of TP53 in MLS/RCLS. Here we analysed four
      MLS/RCLS derived cell lines for TP53 mutations, expression and function. Three
      SV40 transformed cell lines expressed normal TP53 proteins. Irradiation caused
      normal posttranslational modifications of TP53 and induced P21 expression in two
      of these cell lines. Transfection experiments showed that the FUS-DDIT3 fusion
      protein had no effects on irradiation induced TP53 responses. Ion Torrent
      AmpliSeq screening, using the Cancer Hotspot panel, showed no dysfunctional or
      disease associated alleles/mutations. In conclusion, our results suggest that
      most MLS/RCLS cases carry functional TP53 genes and this is consistent with the
      low numbers of secondary mutations observed in this tumor entity. 

PMID- 25393001
TI  - Stomach virtual non-enhanced CT with second-generation, dual-energy CT: a
      preliminary study.
AB  - OBJECTIVES: To compare the true non-enhanced (TNE) and virtual non-enhanced (VNE)
      data sets in patients who underwent gastric preoperative dual-energy CT (DECT)
      and to evaluate potential radiation dose reduction by omitting a TNE scan.
      METHODS: A total of 74 patients underwent gastric DECT. The mean CT values,
      length, image quality and effective radiation doses for VNE and TNE images were
      compared. RESULTS: There was no statistical difference in maximal thickness of
      gastric tumors and maximal diameter of enlarged lymph nodes among the TNE and VNE
      images (P>0.05). The mean CT value differences between TNE and VNE were
      statistically significant for all tissue types, except for aorta attenuation
      measurements (P<0.05), but the absolute differences were under 10 HU. Lower noise
      was found for VNE images than TNE images (P<0.01). Image quality of VNE was
      diagnostic but lower than that of TNE (P<0.01). The dose reduction achieved by
      omitting the TNE acquisition was 21.40 +/- 4.44%. CONCLUSION: VNE scan may
      potentially replace TNE as part of a multi-phase gastric preoperative staging
      imaging protocol with consequent saving in radiation dose.

PMID- 25393002
TI  - Systematic comparison of the effects of alpha-synuclein mutations on its
      oligomerization and aggregation.
AB  - Aggregation of alpha-synuclein (ASYN) in Lewy bodies and Lewy neurites is the
      typical pathological hallmark of Parkinson's disease (PD) and other
      synucleinopathies. Furthermore, mutations in the gene encoding for ASYN are
      associated with familial and sporadic forms of PD, suggesting this protein plays
      a central role in the disease. However, the precise contribution of ASYN to
      neuronal dysfunction and death is unclear. There is intense debate about the
      nature of the toxic species of ASYN and little is known about the molecular
      determinants of oligomerization and aggregation of ASYN in the cell. In order to
      clarify the effects of different mutations on the propensity of ASYN to
      oligomerize and aggregate, we assembled a panel of 19 ASYN variants and compared
      their behaviour. We found that familial mutants linked to PD (A30P, E46K, H50Q,
      G51D and A53T) exhibited identical propensities to oligomerize in living cells,
      but had distinct abilities to form inclusions. While the A30P mutant reduced the
      percentage of cells with inclusions, the E46K mutant had the opposite effect.
      Interestingly, artificial proline mutants designed to interfere with the helical
      structure of the N-terminal domain, showed increased propensity to form
      oligomeric species rather than inclusions. Moreover, lysine substitution mutants
      increased oligomerization and altered the pattern of aggregation. Altogether, our
      data shed light into the molecular effects of ASYN mutations in a cellular
      context, and established a common ground for the study of genetic and
      pharmacological modulators of the aggregation process, opening new perspectives
      for therapeutic intervention in PD and other synucleinopathies.

PMID- 25393003
TI  - Serological investigation of food specific immunoglobulin G antibodies in
      patients with inflammatory bowel diseases.
AB  - OBJECTIVE: Dietary factors have been indicated to influence the pathogenesis and
      nature course of inflammatory bowel diseases (IBD) with their wide variances. The
      aim of the study was to assess the prevalence and clinical significance of 14
      serum food specific immunoglobulin G (sIgG) antibodies in patients with IBD.
      METHODS: This retrospective study comprised a total of 112 patients with IBD,
      including 79 with Crohn's disease (CD) and 33 with ulcerative colitis (UC).
      Medical records, clinical data and laboratory results were collected for
      analysis. Serum IgG antibodies against 14 unique food allergens were detected by
      semi-quantitative enzyme linked immunosorbent assay (ELISA). RESULTS: Food sIgG
      antibodies were detected in 75.9% (60/79) of CD patients, 63.6% (21/33) of UC
      patients and 33.1% (88/266) of healthy controls (HC). IBD patients showed the
      significantly higher antibodies prevalence than healthy controls (CD vs. HC, P =
      0.000; UC vs. HC, P = 0.001). However no marked difference was observed between
      CD and UC groups (P = 0.184). More subjects were found with sensitivity to
      multiple antigens (>= 3) in IBD than in HC group (33.9% vs.0.8%, P = 0.000). Egg
      was the most prevalent food allergen. There was a remarkable difference in the
      levels of general serum IgM (P = 0.045) and IgG (P = 0.041) between patients with
      positive and negative sIgG antibodies. Patients with multiple positive allergens
      (>= 3) were especially found with significant higher total IgG levels compared
      with sIgG-negative patients (P = 0.003). Age was suggested as a protective factor
      against the occurrence of sIgG antibodies (P = 0.002). CONCLUSIONS: The study
      demonstrates a high prevalence of serum IgG antibodies to specific food allergens
      in patients with IBD. sIgG antibodies may potentially indicate disease status in
      clinical and be utilized to guide diets for patients.

PMID- 25393004
TI  - Plasticity between MyoC- and MyoA-glideosomes: an example of functional
      compensation in Toxoplasma gondii invasion.
AB  - The glideosome is an actomyosin-based machinery that powers motility in
      Apicomplexa and participates in host cell invasion and egress from infected
      cells. The central component of the glideosome, myosin A (MyoA), is a motor
      recruited at the pellicle by the acylated gliding-associated protein GAP45. In
      Toxoplasma gondii, GAP45 also contributes to the cohesion of the pellicle,
      composed of the inner membrane complex (IMC) and the plasma membrane, during
      motor traction. GAP70 was previously identified as a paralog of GAP45 that is
      tailored to recruit MyoA at the apical cap in the coccidian subgroup of the
      Apicomplexa. A third member of this family, GAP80, is demonstrated here to
      assemble a new glideosome, which recruits the class XIV myosin C (MyoC) at the
      basal polar ring. MyoC shares the same myosin light chains as MyoA and also
      interacts with the integral IMC proteins GAP50 and GAP40. Moreover, a central
      component of this complex, the IMC-associated protein 1 (IAP1), acts as the key
      determinant for the restricted localization of MyoC to the posterior pole.
      Deletion of specific components of the MyoC-glideosome underscores the
      installation of compensatory mechanisms with components of the MyoA-glideosome.
      Conversely, removal of MyoA leads to the relocalization of MyoC along the
      pellicle and at the apical cap that accounts for residual invasion. The two
      glideosomes exhibit a considerable level of plasticity to ensure parasite
      survival. 

PMID- 25393005
TI  - A neural population model incorporating dopaminergic neurotransmission during
      complex voluntary behaviors.
AB  - Assessing brain activity during complex voluntary motor behaviors that require
      the recruitment of multiple neural sites is a field of active research. Our
      current knowledge is primarily based on human brain imaging studies that have
      clear limitations in terms of temporal and spatial resolution. We developed a
      physiologically informed non-linear multi-compartment stochastic neural model to
      simulate functional brain activity coupled with neurotransmitter release during
      complex voluntary behavior, such as speech production. Due to its state-dependent
      modulation of neural firing, dopaminergic neurotransmission plays a key role in
      the organization of functional brain circuits controlling speech and language and
      thus has been incorporated in our neural population model. A rigorous
      mathematical proof establishing existence and uniqueness of solutions to the
      proposed model as well as a computationally efficient strategy to numerically
      approximate these solutions are presented. Simulated brain activity during the
      resting state and sentence production was analyzed using functional network
      connectivity, and graph theoretical techniques were employed to highlight
      differences between the two conditions. We demonstrate that our model
      successfully reproduces characteristic changes seen in empirical data between the
      resting state and speech production, and dopaminergic neurotransmission evokes
      pronounced changes in modeled functional connectivity by acting on the underlying
      biological stochastic neural model. Specifically, model and data networks in both
      speech and rest conditions share task-specific network features: both the
      simulated and empirical functional connectivity networks show an increase in
      nodal influence and segregation in speech over the resting state. These
      commonalities confirm that dopamine is a key neuromodulator of the functional
      connectome of speech control. Based on reproducible characteristic aspects of
      empirical data, we suggest a number of extensions of the proposed methodology
      building upon the current model. 

PMID- 25393006
TI  - Development and validation of an instrument for measuring the quality of teamwork
      in teaching teams in postgraduate medical training (TeamQ).
AB  - BACKGROUND: Teamwork between clinical teachers is a challenge in postgraduate
      medical training. Although there are several instruments available for measuring
      teamwork in health care, none of them are appropriate for teaching teams. The aim
      of this study is to develop an instrument (TeamQ) for measuring teamwork, to
      investigate its psychometric properties and to explore how clinical teachers
      assess their teamwork. METHOD: To select the items to be included in the TeamQ
      questionnaire, we conducted a content validation in 2011, using a Delphi
      procedure in which 40 experts were invited. Next, for pilot testing the
      preliminary tool, 1446 clinical teachers from 116 teaching teams were requested
      to complete the TeamQ questionnaire. For data analyses we used statistical
      strategies: principal component analysis, internal consistency reliability
      coefficient, and the number of evaluations needed to obtain reliable estimates.
      Lastly, the median TeamQ scores were calculated for teams to explore the levels
      of teamwork. RESULTS: In total, 31 experts participated in the Delphi study. In
      total, 114 teams participated in the TeamQ pilot. The median team response was 7
      evaluations per team. The principal component analysis revealed 11 factors; 8
      were included. The reliability coefficients of the TeamQ scales ranged from 0.75
      to 0.93. The generalizability analysis revealed that 5 to 7 evaluations were
      needed to obtain internal reliability coefficients of 0.70. In terms of teamwork,
      the clinical teachers scored residents' empowerment as the highest TeamQ scale
      and feedback culture as the area that would most benefit from improvement.
      CONCLUSIONS: This study provides initial evidence of the validity of an
      instrument for measuring teamwork in teaching teams. The high response rates and
      the low number of evaluations needed for reliably measuring teamwork indicate
      that TeamQ is feasible for use by teaching teams. Future research could explore
      the effectiveness of feedback on teamwork in follow up measurements.

PMID- 25393007
TI  - Function-triggering antibodies to the adhesion molecule L1 enhance recovery after
      injury of the adult mouse femoral nerve.
AB  - L1 is among the few adhesion molecules that favors repair after trauma in the
      adult central nervous system of vertebrates by promoting neuritogenesis and
      neuronal survival, among other beneficial features. In the peripheral nervous
      system, L1 is up-regulated in Schwann cells and regrowing axons after nerve
      damage, but the functional consequences of this expression remain unclear. Our
      previous study of L1-deficient mice in a femoral nerve injury model showed an
      unexpected improved functional recovery, attenuated motoneuronal cell death, and
      enhanced Schwann cell proliferation, being attributed to the persistent synthesis
      of neurotrophic factors. On the other hand, transgenic mice over-expressing L1 in
      neurons led to improved remyelination, but not improved functional recovery. The
      present study was undertaken to investigate whether the monoclonal L1 antibody
      557 that triggers beneficial L1 functions in vitro would trigger these also in
      femoral nerve repair. We analyzed femoral nerve regeneration in C57BL/6J mice
      that received this antibody in a hydrogel filled conduit connecting the cut and
      sutured nerve before its bifurcation, leading to short-term release of antibody
      by diffusion. Video-based quantitative analysis of motor functions showed
      improved recovery when compared to mice treated with conduits containing PBS in
      the hydrogel scaffold, as a vehicle control. This improved recovery was
      associated with attenuated motoneuron loss, remyelination and improved precision
      of preferential motor reinnervation. We suggest that function-triggering L1
      antibodies applied to the lesion site at the time of injury over a limited time
      period will not only be beneficial in peripheral, but also central nervous system
      regeneration. 

PMID- 25393008
TI  - Leishmania infantum ecto-nucleoside triphosphate diphosphohydrolase-2 is an
      apyrase involved in macrophage infection and expressed in infected dogs.
AB  - BACKGROUND: Visceral leishmaniasis is an important tropical disease, and
      Leishmania infantum chagasi (synonym of Leishmania infantum) is the main
      pathogenic agent of visceral leishmaniasis in the New World. Recently, ecto
      nucleoside triphosphate diphosphohydrolases (E-NTPDases) were identified as
      enablers of infection and virulence factors in many pathogens. Two putative E
      NTPDases (~70 kDa and ~45 kDa) have been found in the L. infantum genome. Here,
      we studied the ~45 kDa E-NTPDase from L. infantum chagasi to describe its natural
      occurrence, biochemical characteristics and influence on macrophage infection.
      METHODOLOGY/PRINCIPAL FINDINGS: We used live L. infantum chagasi to demonstrate
      its natural ecto-nucleotidase activity. We then isolated, cloned and expressed
      recombinant rLicNTPDase-2 in bacterial system. The recombinant rLicNTPDase-2
      hydrolyzed a wide variety of triphosphate and diphosphate nucleotides (GTP> GDP 
      =  UDP> ADP> UTP  =  ATP) in the presence of calcium or magnesium. In addition,
      rLicNTPDase-2 showed stable activity over a pH range of 6.0 to 9.0 and was
      partially inhibited by ARL67156 and suramin. Microscopic analyses revealed the
      presence of this protein on cell surfaces, vesicles, flagellae, flagellar
      pockets, kinetoplasts, mitochondria and nuclei. The blockade of E-NTPDases using
      antibodies and competition led to lower levels of parasite adhesion and infection
      of macrophages. Furthermore, immunohistochemistry showed the expression of E
      NTPDases in amastigotes in the lymph nodes of naturally infected dogs from an
      area of endemic visceral leishmaniasis. CONCLUSIONS/SIGNIFICANCE: In this work,
      we cloned, expressed and characterized the NTPDase-2 from L. infantum chagasi and
      demonstrated that it functions as a genuine enzyme from the E-NTPDase/CD39
      family. We showed that E-NTPDases are present on the surface of promastigotes and
      in other intracellular locations. We showed, for the first time, the broad
      expression of LicNTPDases in naturally infected dogs. Additionally, the blockade
      of NTPDases led to lower levels of in vitro adhesion and infection, suggesting
      that these proteins are possible targets for rational drug design.

PMID- 25393009
TI  - Evaluation of the diagnostic performance of magnetic resonance spectroscopy in
      brain tumors: a systematic review and meta-analysis.
AB  - OBJECT: The aim of this study was to determine the suitability of magnetic
      resonance spectroscopy (MRS) for screening brain tumors, based on a systematic
      review and meta-analysis of published data on the diagnostic performance of MRS.
      METHODS: The PubMed and PHMC databases were systematically searched for relevant
      studies up to December 2013. The sensitivities and specificities of MRS in
      individual studies were calculated and the pooled diagnostic accuracies, with 95%
      confidence intervals (CI), were assessed under a fixed-effects model. RESULTS:
      Twenty-four studies were included, comprising a total of 1013 participants.
      Overall, no heterogeneity of diagnostic effects was observed between studies. The
      pooled sensitivity and specificity of MRS were 80.05% (95% CI = 75.97%-83.59%)
      and 78.46% (95% CI: 73.40%-82.78%), respectively. The area under the summary
      receiver operating characteristic curve was 0.78. Stratified meta analysis showed
      higher sensitivity and specificity in child than adult. CSI had higher
      sensitivity and SV had higher specificity. Higher sensitivity and specificity
      were obtained in short TE value. CONCLUSION: Although the qualities of the
      studies included in the meta-analysis were moderate, current evidence suggests
      that MRS may be a valuable adjunct to magnetic resonance imaging for diagnosing
      brain tumors, but requires selection of suitable technique and TE value.

PMID- 25393010
TI  - ATPase-independent type-III protein secretion in Salmonella enterica.
AB  - Type-III protein secretion systems are utilized by gram-negative pathogens to
      secrete building blocks of the bacterial flagellum, virulence effectors from the
      cytoplasm into host cells, and structural subunits of the needle complex. The
      flagellar type-III secretion apparatus utilizes both the energy of the proton
      motive force and ATP hydrolysis to energize substrate unfolding and
      translocation. We report formation of functional flagella in the absence of type
      III ATPase activity by mutations that increased the proton motive force and
      flagellar substrate levels. We additionally show that increased proton motive
      force bypassed the requirement of the Salmonella pathogenicity island 1 virulence
      associated type-III ATPase for secretion. Our data support a role for type-III
      ATPases in enhancing secretion efficiency under limited secretion substrate
      concentrations and reveal the dispensability of ATPase activity in the type-III
      protein export process. 

PMID- 25393012
TI  - Is it that time already?

PMID- 25393011
TI  - Seasonal variability in airborne biotic contaminants in swine confinement
      buildings.
AB  - Little is known about the seasonal dynamics of biotic contaminants in swine
      confinement buildings (SCBs). The biotic contaminants of seven SCBs were
      monitored during one visit in the winter and one during the summer. Paired-end
      Illumina sequencing of the 16S rRNA gene, V3 region, was used to examine seasonal
      shifts in bacterial community composition and diversity. The abundances of 16S
      rRNA genes and six tetracycline resistance genes (tetB, tetH, tetZ, tetO, tetQ,
      and tetW) were also quantified using real-time PCR. Bacterial abundances,
      community composition and diversity all showed strong seasonal patterns defined
      by winter peaks in abundance and diversity. Microclimatic variables of SCBs,
      particularly air speed, PM2.5 and total suspended particles (TSP) were found
      significantly correlated to abundances, community composition, and diversity of
      bacterial bioaerosols. Seasonal fluctuations were also observed for four
      tetracycline resistance genes, tetH, tetO, tetQ, and tetW. The frequency of
      occurrences of these resistance genes were significantly higher in samples
      collected during winter and was also significantly correlated with air speed,
      PM2.5 and TSP. Overall, our results indicate that biotic contaminants in SCBs
      exhibit seasonal trends, and these could be associated with the microclimatic
      variables of SCBs. The correlations established in the current study could be
      helpful in establishing better management strategies to minimize the potential
      health impacts on both livestock and humans working in this environment. 

PMID- 25393013
TI  - Effects of regular away travel on training loads, recovery, and injury rates in
      professional Australian soccer players.
AB  - The current study examined the acute and longitudinal effects of regular away
      travel on training load (TL), player wellness, and injury surrounding competitive
      football (soccer) matches. Eighteen male professional football players,
      representing a team competing in the highest national competition in Australia,
      volunteered to participate in the study. Training loads, player wellness and
      injury incidence, rate, severity, and type, together with the activity at the
      time of injury, were recorded on the day before, the day of, and for 4 d after
      each of the 27 matches of the 2012-13 season. This included 14 home and 13 away
      matches, further subdivided based on the midpoint of the season into early (1-13)
      and late competition (14-27) phases. While TLs were significantly greater on day
      3 at home compared with away during the early competition phase (P=.03), no other
      significant effects of match location were identified (P>.05). Total TL and mean
      wellness over the 6 d surrounding matches and TL on day 3 were significantly
      reduced during the late compared with the early competition phase at home and
      away (P<.05). Although not significantly (P>.05), training missed due to injury
      was 60% and 50% greater during the late than during the early competition phase
      at home and away, respectively. In conclusion, no significant interactions
      between match location and competition phase were evident during the late
      competition phase, which suggests that away travel had negligible cumulative
      effects on the reduction in player wellness in the latter half of the season.

PMID- 25393014
TI  - Chloroplast protrusions in leaves of Ranunculus glacialis L. respond
      significantly to different ambient conditions, but are not related to temperature
      stress.
AB  - The occurrence of chloroplast protrusions (CPs) in leaves of Ranunculus glacialis
      L. in response to different environmental conditions was assessed. CPs occur
      highly dynamically. They do not contain thylakoids and their physiological
      function is still largely unknown. Controlled in situ sampling showed that CP
      formation follows a pronounced diurnal rhythm. Between 2 and 27  degrees C the
      relative proportion of chloroplasts with CPs (rCP) showed a significant positive
      correlation to leaf temperature (TL; 0.793, P < 0.01), while irradiation
      intensity had a minor effect on rCP. In situ shading and controlled laboratory
      experiments confirmed the significant influence of TL. Under moderate irradiation
      intensity, an increase of TL up to 25  degrees C significantly promoted CP
      formation, while a further increase to 37  degrees C led to a decrease.
      Furthermore, rCP values were lower in darkness and under high irradiation
      intensity. Gas treatment at 2000 ppm CO2/2% O2 led to a significant decrease of
      rCP, suggesting a possible involvement of photorespiration in CP formation. Our
      findings demonstrate that in R. glacialis, CPs are neither a rare phenomenon nor
      a result of heat or light stress; on the contrary, they seem to be most abundant
      under moderate temperature and non-stress irradiation conditions.

PMID- 25393015
TI  - Bulk charge carrier transport in push-pull type organic semiconductor.
AB  - Operation of organic electronic and optoelectronic devices relies on charge
      transport properties of active layer materials. The magnitude of charge carrier
      mobility, a key efficiency metrics of charge transport properties, is determined
      by the chemical structure of molecular units and their crystallographic packing
      motifs, as well as strongly depends on the film fabrication approaches that
      produce films with different degrees of anisotropy and structural order. Probed
      by the time-of-flight and grazing incidence X-ray diffraction techniques, bulk
      charge carrier transport, molecular packing, and film morphology in different
      structural phases of push-pull type organic semiconductor, 7,7'-(4,4-bis(2
      ethylhexyl)-4H-silolo[3,2-b:4,5-b']dithiophene-2,6-diyl)bis(6-fluoro-4-(5'-hexyl
      [2,2'-bithiophen]-5yl)benzo[c][1,2,5] thiadiazole), one of the most efficient
      small-molecule photovoltaic materials to-date, are described herein. In the
      isotropic phase, the material is ambipolar with high mobilities for a fluid
      state. The electron and hole mobilities at the phase onset at 210.78  degrees C
      are 1.0 * 10(-3) cm(2)/(V s) and 6.5 * 10(-4) cm(2)/(V s), respectively. Analysis
      of the temperature and electric field dependences of the mobilities in the
      framework of Gaussian disorder formalism suggests larger energetic and positional
      disorder for electron transport sites. Below 210  degrees C, crystallization into
      a polycrystalline film with a triclinic unit cell symmetry and high degree of
      anisotropy leads to a 10-fold increase of hole mobility. The mobility is limited
      by the charge transfer along the direction of branched alkyl side chains. Below
      90  degrees C, faster cooling rates produce even higher hole mobilities up to 2 *
      10(-2) cm(2)/(V s) at 25  degrees C because of the more isotropic orientations of
      crystalline domains. These properties facilitate in understanding efficient
      material performance in photovoltaic devices and will guide further development
      of materials and devices. 

PMID- 25393016
TI  - Aging increases the susceptivity of MSCs to reactive oxygen species and impairs
      their therapeutic potency for myocardial infarction.
AB  - Myocardial infarction (MI) is one of the leading causes of death worldwide and
      Mesenchymal Stem Cells (MSCs) transplantation has been considered a promising
      therapy. Recently, it was reported that the therapeutic effectiveness of MSCs is
      dependent on the age of the donor, yet the underlying mechanism has not been
      thoroughly investigated. This study was designed to investigate whether this
      impaired therapeutic potency is caused by an increased susceptivity of MSCs from
      old donors to reactive oxygen species (ROS). The MSCs were isolated from the
      subcutaneous inguinal region of young (8-10 weeks) and old (18 months) Sprague
      Dawley (SD) rats. By exposing these MSCs to H2O2, we found that the adhesion of
      MSCs from old donors was damaged more severely. Specifically, decreased
      expression of integrin and reduced phosphorylation of focal adhesion kinase Src
      and FAK were observed. Furthemore, H2O2 triggered an increased apoptosis of MSCs
      from old donors. To study the viability and therapeutic potency of MSCs from
      young and old donors in vivo, these MSCs were transplanted into acute MI model
      rats. We observed a more rapidly decreased survival rate of the old MSCs in the
      infarct region, which may be caused by their increased susceptivity to the micro
      environmental ROS, as transplantation of the old MSCs with N-acetyl-L-cysteine
      (NAC), a ROS scavenger, protected them. The low viability of engrafted old MSCs
      consequently impaired their therapeutic effectiveness, judging by the histology
      and function of heart. Our study may help to understand the mechanism of MSCs
      host interaction during MI, as well as shed light on the design of therapeutic
      strategy in clinic. 

PMID- 25393017
TI  - An immunohistochemical analysis to validate the rationale behind the enhanced
      immunogenicity of D-ribosylated low density lipo-protein.
AB  - Advanced glycation end products (AGEs) are thought to contribute to the abnormal
      lipoprotein profiles and increased risk of cardiovascular disease in patients
      with diabetes and renal failure. D-ribose is one of the naturally occurring
      pentose monosaccharide present in all living cells and is a key component of
      numerous biomolecules involved in many important metabolic pathways. Formation of
      D-ribose derived glycated low density lipoprotein (LDL) has been previously
      demonstrated but no studies have been performed to assess the immune complex
      deposition in the kidney of rabbits immunized with glycated LDL. In this study,
      LDL was glycated with D-ribose, and it was further used as an immunogen for
      immunizing NZW female rabbits. The results showed that female rabbits immunized
      with D-ribose modified LDL induced antibodies as detected by direct binding and
      competitive ELISA. The modified LDL was found to be highly immunogenic eliciting
      high titer immunogen-specific antibodies, while the native forms were moderately
      immunogenic. The induced antibodies from modified LDL exhibited wide range of
      heterogeneity in recognizing various proteins and amino acids conformers.
      Furthermore, our histopathological results illustrated the deposits of immune
      complex in glomerular basement membrane in rabbits immunized with D-ribose-LDL. 

PMID- 25393018
TI  - FRET-FLIM investigation of PSD95-NMDA receptor interaction in dendritic spines;
      control by calpain, CaMKII and Src family kinase.
AB  - Little is known about the changes in protein interactions inside synapses during
      synaptic remodeling, as their live monitoring in spines has been limited. We used
      a FRET-FLIM approach in developing cultured rat hippocampal neurons expressing
      fluorescently tagged NMDA receptor (NMDAR) and PSD95, two essential proteins in
      synaptic plasticity, to examine the regulation of their interaction. NMDAR
      stimulation caused a transient decrease in FRET between the NMDAR and PSD95 in
      spines of young and mature neurons. The activity of both CaMKII and calpain were
      essential for this effect in both developmental stages. Meanwhile, inhibition of
      Src family kinase (SFK) had opposing impacts on this decrease in FRET in young
      versus mature neurons. Our data suggest concerted roles for CaMKII, SFK and
      calpain activity in regulating activity-dependent separation of PSD95 from GluN2A
      or GluN2B. Finally, we found that calpain inhibition reduced spine growth that
      was caused by NMDAR activity, supporting the hypothesis that PSD95-NMDAR
      separation is implicated in synaptic remodeling. 

PMID- 25393020
TI  - Confirmation through genetic analysis of the existence of many local phyloclades
      of the genus Simocephalus (Crustacea, Cladocera) in China.
AB  - Previously, a series of Simocephalus taxa (Cladocera: Daphniidae) from China were
      described. Most were proposed to be junior synonyms in the last revision of the
      genus. Using original material from China and data from GenBank, we investigate
      the biodiversity and phylogeny of Simocephalus using sequences of the cytochrome
      c oxidase subunit I (COI) and the nuclear 18S genes. In both cases, neighbor
      joining, maximum likelihood and Bayesian inference analyses led to highly
      congruent tree topologies. The grouping of the deeper clades agrees with the
      inter-generic classification of Orlova-Bienkowskaja (2001). Only the populations
      of S. serrulatus from Eurasia and North America seem to be closely related, and
      there are no other shared species between the two continents. Our study
      unambiguously confirms the existence of many lineages from the subgenera of
      Simocephalus (Echinocaudus) and Simocephalus s.str. in China, but their
      morphology needs to be reexamined by taking a wider range of characters (e.g., of
      female thoracic limbs and adult males) into consideration. 

PMID- 25393019
TI  - PUL21a-Cyclin A2 interaction is required to protect human cytomegalovirus
      infected cells from the deleterious consequences of mitotic entry.
AB  - Entry into mitosis is accompanied by dramatic changes in cellular architecture,
      metabolism and gene expression. Many viruses have evolved cell cycle arrest
      strategies to prevent mitotic entry, presumably to ensure sustained,
      uninterrupted viral replication. Here we show for human cytomegalovirus (HCMV)
      what happens if the viral cell cycle arrest mechanism is disabled and cells
      engaged in viral replication enter into unscheduled mitosis. We made use of an
      HCMV mutant that, due to a defective Cyclin A2 binding motif in its UL21a gene
      product (pUL21a), has lost its ability to down-regulate Cyclin A2 and, therefore,
      to arrest cells at the G1/S transition. Cyclin A2 up-regulation in infected cells
      not only triggered the onset of cellular DNA synthesis, but also promoted the
      accumulation and nuclear translocation of Cyclin B1-CDK1, premature chromatin
      condensation and mitotic entry. The infected cells were able to enter metaphase
      as shown by nuclear lamina disassembly and, often irregular, metaphase spindle
      formation. However, anaphase onset was blocked by the still intact anaphase
      promoting complex/cyclosome (APC/C) inhibitory function of pUL21a. Remarkably,
      the essential viral IE2, but not the related chromosome-associated IE1 protein,
      disappeared upon mitotic entry, suggesting an inherent instability of IE2 under
      mitotic conditions. Viral DNA synthesis was impaired in mitosis, as demonstrated
      by the abnormal morphology and strongly reduced BrdU incorporation rates of viral
      replication compartments. The prolonged metaphase arrest in infected cells
      coincided with precocious sister chromatid separation and progressive
      fragmentation of the chromosomal material. We conclude that the Cyclin A2-binding
      function of pUL21a contributes to the maintenance of a cell cycle state conducive
      for the completion of the HCMV replication cycle. Unscheduled mitotic entry
      during the course of the HCMV replication has fatal consequences, leading to
      abortive infection and cell death. 

PMID- 25393021
TI  - High variability in oral glucose tolerance among 1,128 patients with cystic
      fibrosis: a multicenter screening study.
AB  - BACKGROUND: In cystic fibrosis, highly variable glucose tolerance is suspected.
      However, no study provided within-patient coefficients of variation. The main
      objective of this short report was to evaluate within-patient variability of oral
      glucose tolerance. METHODS: In total, 4,643 standardized oral glucose tolerance
      tests of 1,128 cystic fibrosis patients (median age at first test: 15.5 [11.5;
      21.5] years, 48.8% females) were studied. Patients included were clinically
      stable, non-pregnant, and had at least two oral glucose tolerance tests, with no
      prior lung transplantation or systemic steroid therapy. Transition frequency from
      any one test to the subsequent test was analyzed and within-patient coefficients
      of variation were calculated for fasting and two hour blood glucose values. All
      statistical analysis was implemented with SAS 9.4. RESULTS: A diabetic glucose
      tolerance was confirmed in 41.2% by the subsequent test. A regression to normal
      glucose tolerance at the subsequent test was observed in 21.7% and to impaired
      fasting glucose, impaired glucose tolerance or both in 15.2%, 12.0% or 9.9%. The
      average within-patient coefficient of variation for fasting blood glucose was
      11.1% and for two hour blood glucose 25.3%. CONCLUSION: In the cystic fibrosis
      patients studied, a highly variable glucose tolerance was observed. Compared to
      the general population, variability of two hour blood glucose was 1.5 to 1.8-fold
      higher.

PMID- 25393023
TI  - Achieving population-level immunity to rabies in free-roaming dogs in Africa and
      Asia.
AB  - Canine rabies can be effectively controlled by vaccination with readily
      available, high-quality vaccines. These vaccines should provide protection from
      challenge in healthy dogs, for the claimed period, for duration of immunity,
      which is often two or three years. It has been suggested that, in free-roaming
      dog populations where rabies is endemic, vaccine-induced protection may be
      compromised by immuno-suppression through malnutrition, infection and other
      stressors. This may reduce the proportion of dogs that seroconvert to the vaccine
      during vaccination campaigns and the duration of immunity of those dogs that
      seroconvert. Vaccination coverage may also be limited through insufficient
      vaccine delivery during vaccination campaigns and the loss of vaccinated
      individuals from populations through demographic processes. This is the first
      longitudinal study to evaluate temporal variations in rabies vaccine-induced
      serological responses, and factors associated with these variations, at the
      individual level in previously unvaccinated free-roaming dog populations.
      Individual-level serological and health-based data were collected from three
      cohorts of dogs in regions where rabies is endemic, one in South Africa and two
      in Indonesia. We found that the vast majority of dogs seroconverted to the
      vaccine; however, there was considerable variation in titres, partly attributable
      to illness and lactation at the time of vaccination. Furthermore, >70% of the
      dogs were vaccinated through community engagement and door-to-door vaccine
      delivery, even in Indonesia where the majority of the dogs needed to be caught by
      net on successive occasions for repeat blood sampling and vaccination. This
      demonstrates the feasibility of achieving population-level immunity in free
      roaming dog populations in rabies-endemic regions. However, attrition of immune
      individuals through demographic processes and waning immunity necessitates repeat
      vaccination of populations within at least two years to ensure communities are
      protected from rabies. These findings support annual mass vaccination campaigns
      as the most effective means to control canine rabies. 

PMID- 25393024
TI  - Hyaluronidase modulates inflammatory response and accelerates the cutaneous wound
      healing.
AB  - Hyaluronidases are enzymes that degrade hyaluronan an important constituent of
      the extracellular matrix. They have been used as a spreading agent, improving the
      absorption of drugs and facilitating the subcutaneous infusion of fluids. Here,
      we investigated the influence of bovine testes hyaluronidase (HYAL) during
      cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the
      wound scratch assay that HYAL increased the migration and proliferation of
      fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell
      number by 20%. HYAL presented faster and higher reepithelialization in in vivo
      full-thickness excisional wounds generated on adult Wistar rats back skin already
      in the early phase at 2nd day post operatory compared to vehicle-control group.
      Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38%
      and 46% compared to 19% in the controls, respectively. Histological and
      biochemical analyses supported the clinical observations and showed that HYAL
      treated wounds exhibited increased granulation tissue, diminished edema formation
      and regulated the inflammatory response by modulating the release of pro and anti
      inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL
      increased gene expression of peroxisome proliferator-activated receptors (PPAR)
      gamma and PPAR beta/delta, the collagen content in the early stages of healing
      processes as well as angiogenesis. Altogether these data revealed that HYAL
      accelerates wound healing processes and might be beneficial for treating wound
      disorders. 

PMID- 25393025
TI  - Redifferentiation of adult human beta cells expanded in vitro by inhibition of
      the WNT pathway.
AB  - In vitro expansion of adult human islet beta cells is an attractive solution for
      the shortage of tissue for cell replacement therapy of type 1 diabetes. Using a
      lineage tracing approach we have demonstrated that beta-cell-derived (BCD) cells
      rapidly dedifferentiate in culture and can proliferate for up to 16 population
      doublings. Dedifferentiation is associated with changes resembling epithelial
      mesenchymal transition (EMT). The WNT pathway has been shown to induce EMT and
      plays key roles in regulating replication and differentiation in many cell types.
      Here we show that BCD cell dedifferentiation is associated with beta-catenin
      translocation into the nucleus and activation of the WNT pathway. Inhibition of
      beta-catenin expression in expanded BCD cells using short hairpin RNA resulted in
      growth arrest, mesenchymal-epithelial transition, and redifferentiation, as
      judged by activation of beta-cell gene expression. Furthermore, inhibition of
      beta-catenin expression synergized with redifferentiation induced by a
      combination of soluble factors, as judged by an increase in the number of C
      peptide-positive cells. Simultaneous inhibition of the WNT and NOTCH pathways
      also resulted in a synergistic effect on redifferentiation. These findings, which
      were reproducible in cells derived from multiple human donors, suggest that
      inhibition of the WNT pathway may contribute to a therapeutically applicable way
      for generation of functional insulin-producing cells following ex-vivo expansion.

PMID- 25393026
TI  - Regularized machine learning in the genetic prediction of complex traits.

PMID- 25393027
TI  - Assessing the utility of ICU readmissions as a quality metric: an analysis of
      changes mediated by residency work-hour reforms.
AB  - BACKGROUND: ICU readmissions are associated with increased mortality and costs;
      however, it is unclear whether these outcomes are caused by readmissions or by
      residual confounding by illness severity. An assessment of temporal changes in
      ICU readmission in response to a specific policy change could help disentangle
      these possibilities. We sought to determine whether ICU readmission rates changed
      after 2003 Accreditation Council for Graduate Medical Education Resident Duty
      Hours reform ("reform") and whether there were temporally corresponding changes
      in other ICU outcomes. METHODS: We used a difference-in-differences approach
      using Project IMPACT (Improved Methods of Patient Information Access of Core
      Clinical Tasks). Piecewise regression models estimated changes in outcomes
      immediately before and after reform in 274,491 critically ill medical and
      surgical patients in 151 community and academic US ICUs. Outcome measures
      included ICU readmission, ICU mortality, and in-hospital post-ICU-discharge
      mortality. RESULTS: In ICUs with residents, ICU readmissions increased before
      reform (OR, 1.5; 95% CI, 1.22-1.84; P < .01), and decreased after (OR, 0.85; 95%
      CI, 0.73-0.98; P = .03). This abrupt decline in ICU readmissions after reform
      differed significantly from an increase in readmissions observed in ICUs without
      residents at this time (difference-in-differences P < .01). No comparable changes
      in mortality were observed between ICUs with vs without residents. CONCLUSIONS:
      The changes in ICU readmission rates after reform, without corresponding changes
      in mortality, suggest that ICU readmissions are not causally related to other
      untoward patient outcomes. Instead, ICU readmission rates likely reflect
      operational aspects of care that are not patient-centered, making them less
      useful indicators of ICU quality.

PMID- 25393028
TI  - A Dyadic Perspective on Speech Accommodation and Social Connection: Both
      Partners' Rejection Sensitivity Matters.
AB  - Findings from confederate paradigms predict that mimicry is an adaptive route to
      social connection for rejection-sensitive individuals (Lakin, Chartrand, & Arkin,
      2008). However, dyadic perspectives predict that whether mimicry leads to
      perceived connection depends on the rejection sensitivity (RS) of both partners
      in an interaction. We investigated these predictions in 50 college women who
      completed a dyadic cooperative task in which members were matched or mismatched
      in being dispositionally high or low in RS. We used a psycholinguistics paradigm
      to assess, through independent listeners' judgments (N = 162), how much
      interacting individuals accommodate phonetic aspects of their speech toward each
      other. Results confirmed predictions from confederate paradigms in matched RS
      dyads. However, mismatched dyads showed an asymmetry in levels of accommodation
      and perceived connection: Those high in RS accommodated more than their low-RS
      partner but emerged feeling less connected. Mediational analyses indicated that
      low-RS individuals' nonaccommodation in mismatched dyads helped explain their
      high-RS partners' relatively low perceived connection to them. Establishing
      whether mimicry is an adaptive route to social connection requires analyzing
      mimicry as a dyadic process influenced by the needs of each dyad member. 

PMID- 25393029
TI  - Kinetic study of the scavenging reaction of the aroxyl radical by seven kinds of
      rice bran extracts in ethanol solution. Development of an aroxyl radical
      absorption capacity (ARAC) assay method.
AB  - Recently, a new assay method that can quantify the aroxyl radical (ArO*)
      absorption capacity (ARAC) of antioxidants (AOHs) was proposed. In the present
      work, the second-order rate constants (ks(Extract)) and ARAC values for the
      reaction of ArO* with seven kinds of rice bran extracts 1-7, which contain
      different concentrations of alpha-, beta-, gamma-, and delta-tocopherols and 
      tocotrienols (alpha-, beta-, gamma-, and delta-Tocs and -Toc-3s) and gamma
      oryzanol, were measured in ethanol at 25  degrees C using stopped-flow
      spectrophotometry. The ks(Extract) value (1.26 * 10(-2) M(-1) s(-1)) of
      Nipponbare (extract 1) with the highest activity was 1.5 times larger than that
      (8.29 * 10(-3)) of Milyang-23 (extract 7) with the lowest activity. The
      concentrations (in mg/100 g) of alpha-, beta-, gamma-, and delta-Tocs and -Toc-3s
      and gamma-oryzanol found in the seven extracts 1-7 were determined using HPLC
      MS/MS and UV-vis absorption spectroscopy, respectively. From the results, it has
      been clarified that the ArO*-scavenging rates (ks(Extract)) (that is, the
      relative ARAC value) obtained for the seven extracts 1-7 may be approximately
      explained as the sum of the product {Sigma ks(AOH-i) [AOH-i]/10(5)} of the rate
      constant (ks(AOH-i)) and the concentration ([AOH-i]/10(5)) of AOH-i (Tocs, Toc
      3s, and gamma-oryzanol) included in rice bran extracts. The contribution of gamma
      oryzanol to the ks(Extract) value was estimated to be between 3.0-4.7% for each
      extract. Taken together, these results suggest that the ARAC assay method is
      applicable to general food extracts. 

PMID- 25393031
TI  - Responses of phyto- and zooplankton communities to Prymnesium polylepis
      (Prymnesiales) bloom in the Baltic Sea.
AB  - A large bloom of Prymnesium polylepis occurred in the Baltic Sea during the
      winter 2007-spring 2008. Based on numerous reports of strong allelopathic effects
      on phytoplankton exerted by P. polylepis and its toxicity to grazers, we
      hypothesized that during this period negative correlations will be observed
      between P. polylepis and (1) main phytoplankton groups contributing to the spring
      bloom (i.e., diatoms and dinoflagellates), and (2) zooplankton growth and
      abundance. To test these hypotheses, we analyzed inter-annual variability in
      phytoplankton and zooplankton dynamics as well as growth indices (RNA:DNA ratio)
      in dominant zooplankton in relation to the Prymnesium abundance and biomass.
      Contrary to the hypothesized relationships, no measurable negative responses to
      P. polylepis were observed for either the total phytoplankton stocks or the
      zooplankton community. The only negative response, possibly associated with P.
      polylepis occurrence, was significantly lower abundance of dinoflagellates both
      during and after the bloom in 2008. Moreover, contrary to the expected negative
      effects, there were significantly higher total phytoplankton abundance as well as
      significantly higher winter abundance and winter-spring RNA:DNA ratio in dominant
      zooplankton species in 2008, indicating that P. polylepis bloom coincided with
      favourable feeding conditions for zooplankton. Thus, primary consumers, and
      consequently also zooplanktivores (e.g., larval fish and mysids), may benefit
      from haptophyte blooms, particularly in winter, when phytoplankton is scarce.

PMID- 25393030
TI  - Power laws from linear neuronal cable theory: power spectral densities of the
      soma potential, soma membrane current and single-neuron contribution to the EEG.
AB  - Power laws, that is, power spectral densities (PSDs) exhibiting 1/f(alpha)
      behavior for large frequencies f, have been observed both in microscopic (neural
      membrane potentials and currents) and macroscopic (electroencephalography; EEG)
      recordings. While complex network behavior has been suggested to be at the root
      of this phenomenon, we here demonstrate a possible origin of such power laws in
      the biophysical properties of single neurons described by the standard cable
      equation. Taking advantage of the analytical tractability of the so called ball
      and stick neuron model, we derive general expressions for the PSD transfer
      functions for a set of measures of neuronal activity: the soma membrane current,
      the current-dipole moment (corresponding to the single-neuron EEG contribution),
      and the soma membrane potential. These PSD transfer functions relate the PSDs of
      the respective measurements to the PSDs of the noisy input currents. With
      homogeneously distributed input currents across the neuronal membrane we find
      that all PSD transfer functions express asymptotic high-frequency 1/f(alpha)
      power laws with power-law exponents analytically identified as alphainfinity(I) =
      1/2 for the soma membrane current, alphainfinity(p) = 3/2 for the current-dipole
      moment, and alphainfinity(V) = 2 for the soma membrane potential. Comparison with
      available data suggests that the apparent power laws observed in the high
      frequency end of the PSD spectra may stem from uncorrelated current sources which
      are homogeneously distributed across the neural membranes and themselves exhibit
      pink (1/f) noise distributions. While the PSD noise spectra at low frequencies
      may be dominated by synaptic noise, our findings suggest that the high-frequency
      power laws may originate in noise from intrinsic ion channels. The significance
      of this finding goes beyond neuroscience as it demonstrates how 1/f(alpha) power
      laws with a wide range of values for the power-law exponent alpha may arise from
      a simple, linear partial differential equation.

PMID- 25393032
TI  - Characterizing the spatial variation of air pollutants and the contributions of
      high emitting vehicles in Pittsburgh, PA.
AB  - We used a mobile measurement platform to characterize a suite of air pollutants
      (black carbon (BC), particle-bound polycyclic aromatic hydrocarbons (PB-PAH),
      benzene, and toluene) in the city of Pittsburgh and surrounding areas. More than
      270 h of data were collected from forty-two sites which were selected based on
      analysis in the geographic information system (GIS). Mobile measurements were
      performed during three different times of day (mornings, afternoons/evenings, and
      overnight) in both winter (November 2011 to February 2012) and summer (June 2012
      to August 2012). Pollutant concentrations were elevated in river valleys by 9%
      (benzene) to 30% (PB-PAH) relative to upland areas. Traffic had strong impacts on
      measured pollutants. PB-PAH and BC concentrations at high traffic sites were a
      factor of 2 and 30% higher than at low traffic sites, respectively. Pollutant
      concentrations were highest in the morning sessions due to a combination of
      traffic and meteorological conditions. The highly time-resolved data indicated
      that elevated pollutant concentrations at high traffic sites were due to short
      duration plume events associated with high emitting vehicles. High emitting
      vehicles contributed up to 70% of the near road PB-PAH and 30% of BC; emissions
      from these vehicles drove substantial spatial variations in BC and PB-PAH
      concentrations. Many high emitting vehicles were presumably diesel trucks or
      buses, because plumes were strongly correlated with truck traffic volume. In
      contrast, PB-PAH and BC in the nonplume background air was weakly correlated with
      traffic, and their spatial patterns were more influenced by terrain and point
      source emissions. The spatial variability in contributions of high emitting
      vehicles suggests that the effect of potential control strategies vary for
      different pollutants and environments. 

PMID- 25393033
TI  - Ocular adnexal diffuse large B-cell lymphoma: a multicenter international study.
AB  - IMPORTANCE: The clinical features of diffuse large B-cell lymphoma (DLBCL)
      subtype of ocular adnexal lymphoma have not previously been evaluated in a large
      cohort to our knowledge. OBJECTIVE: To investigate the clinical features of
      ocular adnexal DLBCL (OA-DLBCL). DESIGN, SETTING, AND PARTICIPANTS: This
      retrospective international cooperative study involved 6 eye cancer centers.
      During 30 years, 106 patients with OA-DLBCL were identified, and 6 were excluded
      from the study. The median follow-up period was 52 months. MAIN OUTCOMES AND
      MEASURES: Overall survival, disease-specific survival (DSS), and progression-free
      survival were the primary end points. RESULTS: One hundred patients with OA-DLBCL
      were included in the study (median age, 70 years), of whom 54 (54.0%) were
      female. The following 3 groups of patients with lymphoma could be identified:
      primary OA-DLBCL (57.0%), OA-DLBCL and concurrent systemic lymphoma (29.0%), and
      ocular adnexal lymphoma relapse of previous systemic lymphoma (14.0%). Of 57
      patients with primary OA-DLBCL, 53 (93.0%) had Ann Arbor stage IE disease, and 4
      (7.0%) had Ann Arbor stage IIE disease. According to the TNM staging system, 43
      of 57 (75.4%) had T2 tumors. Among all patients, the most frequent treatments
      were external beam radiation therapy with or without surgery (31.0%) and
      rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, prednisone
      (CHOP) or rituximab-CHOP-like chemotherapy with or without external beam
      radiation therapy (21.0%). The 5-year overall survival among the entire cohort
      was 36.0% (median, 3.5 years; 95% CI, 2.5-4.5 years). Relapse occurred in 43.9%
      (25 of 57) of patients with primary OA-DLBCL. Increasing T category of the TNM
      staging system was predictive of DSS (P = .04) in primary OA-DLBCL, whereas the
      Ann Arbor staging system was not. However, when taking all 100 patients into
      account, Ann Arbor stage was able to predict DSS (P = .01). Women had a longer
      median DSS than men (9.8 years; 95% CI, 1.9-17.7 years vs 3.3 years; 95% CI, 1.6
      5.0; P = .03). CONCLUSIONS AND RELEVANCE: Most patients with primary OA-DLBCL
      were seen with Ann Arbor stage IE and TNM T2 disease. The 5-year overall survival
      was between 2.5 and 4.5 years, which is the 95% CI around the median of 3.5 years
      in this cohort. Increasing T category appears to be associated with decreased DSS
      among patients with primary OA-DLBCL. When taking all patients into account, sex
      and Ann Arbor stage also seem to be DSS predictors.

PMID- 25393034
TI  - Triple emission from p-dimethylaminobenzonitrile-cucurbit[8]uril triggers the
      elusive excimer emission.
AB  - The intriguing dual-emission behavior of p- dimethylaminobenzonitrile (DMABN) and
      the identity of the associated excited states is, arguably, the most extensively
      investigated and also controversially discussed molecule- specific phenomenon of
      modern photochemistry. We have now found a new, third fluorescence band when
      DMABN is encapsulated within the water-soluble molecular container
      cucurbit[8]uril (CB8). It is centered between the previously observed emissions
      and assigned to the elusive excimer emission from DMABN through 1:2 CB8:DMABN
      complex formation. Heating of the CB8?(DMABN)2 complex from 0 to 100  degrees C
      results in the dissociation of the ternary complex and restoration of the dual
      emission properties of the monomer. Alternatively, monomer emission can be
      obtained by selecting cucurbit[7]uril (CB7), a host homologue that is too small
      to accommodate two DMABN molecules, or by introducing ethyl instead of methyl
      groups at the amino terminus of the aminobenzonitrile guest. 

PMID- 25393035
TI  - Canaloplasty after failed trabeculectomy: a possible option.

PMID- 25393036
TI  - Phacoemulsification Versus Combined Phacoemulsification and Viscogonioplasty in
      Primary Angle-Closure Glaucoma: A Randomized Clinical Trial.
AB  - PURPOSE: To compare the effect of phacoemulsification (Phaco) versus combined
      phacoemulsification and viscogonioplasty (Phaco-VGP) on long-term intraocular
      pressure (IOP) in primary angle-closure glaucoma (PACG). METHODS: In this
      prospective randomized clinical trial, 92 eyes of 82 patients with PACG and
      coexisting cataract were randomized to undergo Phaco alone (46 eyes) or Phaco-VGP
      (45 eyes) and completed the trial. Anterior segment optical coherence tomography
      was performed preoperatively and at 1 year after surgery. Main outcome measures
      were IOP and the number of IOP-lowering medications. RESULTS: Phaco alone reduced
      the mean IOP from a preoperative level of 22.3+/-6.3 to 14.0+/-3.7 mm Hg at 12
      months after surgery (P<0.001). Phaco-VGP reduced the mean IOP from a
      preoperative level of 23.3+/-7.3 to 14.5+/-2.5 mm Hg (P<0.001). There were no
      statistically significant differences between the 2 groups in IOP and number of
      medications at all follow-up times. Trabecular-iris space-area measured by
      anterior segment optical coherence tomography increased significantly after Phaco
      alone and Phaco-VGP. The amount of the increase was higher in the Phaco-VGP.
      Although peripheral anterior synechiae (PAS) extent decreased significantly by
      Phaco alone, Phaco-VGP resulted in significantly greater reduction in PAS extent
      (P=0.004). The only variables that predicted change in IOP in the whole group
      were preoperative IOP (beta=-0.891, P<0.001) and female sex (beta=2.754, P=0.02).
      CONCLUSIONS: Phaco alone and Phaco-VGP resulted in widening of the drainage
      angle, reduction of IOP, and PAS extent in PACG eyes. Phaco-VGP resulted in
      significantly more reduction of PAS and more opening of angle. However, it seems
      that additional VGP has no significant effect on long-term IOP.

PMID- 25393037
TI  - Trabeculectomy With Mitomycin C or Ahmed Valve Implantation in Eyes With Uveitic
      Glaucoma.
AB  - PURPOSE: To report and compare the results of trabeculectomy with mitomycin C
      (MMC) and Ahmed valve implantation in the management of uveitic glaucoma.
      PATIENTS AND METHODS: The records of 41 eyes of 29 patients who underwent
      trabeculectomy with MMC or Ahmed valve implantation for uveitic glaucoma were
      retrospectively reviewed. Seventeen eyes underwent trabeculectomy with MMC, and
      24 eyes underwent Ahmed valve implantation. Outcomes included postoperative
      intraocular pressure (IOP), percent reduction from preoperative IOP,
      postoperative number of medications, time to failure, and complications. RESULTS:
      Mean follow-up was 21.2 months in the trabeculectomy group and 23.8 months in the
      valve group (P=0.06). Mean IOP was reduced from 29.2 to 18.4 mm Hg in the
      trabeculectomy group (31.3%), compared with a reduction from 33.4 to 15.5 mm Hg
      in the Ahmed valve group (42.7%, P=0.53). Postoperatively, 1.76 medications were
      used in the trabeculectomy group, compared with 1.83 medications in the Ahmed
      valve group (P=0.89). Cumulative success at 1 year was 66.7% in the
      trabeculectomy group, compared with 100% in the Ahmed valve group (P=0.02). Mean
      time to failure was 8.36 months with trabeculectomy, and 21.8 months with Ahmed
      valve (P=0.02). Complications in both groups were typically rare and self
      limited, with recurrent inflammation being most common. CONCLUSIONS: Although
      both trabeculectomy with MMC and Ahmed valve implantation are reasonable surgical
      options in the management of uncontrolled uveitic glaucoma, Ahmed valve
      implantation was associated with higher cumulative success rate at 1 year and a
      longer mean time to failure.

PMID- 25393039
TI  - Explantation of the novel Ahmed glaucoma valve M4 implant.
AB  - PURPOSE: To report a series of cases involving Ahmed Glaucoma Valve M4 (AGV)
      explantation and to discuss the surgical technique to remove the drainage device.
      METHODS: Four cases were identified that presented with AGV M4 postoperative
      complications necessitating tube shunt removal. Three patients presented with
      conjunctival erosion and 1 patient with persistent diplopia. AGV M4 implants were
      removed successfully between 1.5 and 9 months after implantation. RESULTS:
      Successful explantation of the AGV M4 novel implant was achieved in all cases
      without intraoperative or postoperative complications. CONCLUSIONS: If necessary,
      AGV M4 explantation can be successfully performed in the early postoperative
      period.

PMID- 25393038
TI  - Efficacy of Adjunctive Subconjunctival Bevacizumab on the Outcomes of Primary
      Trabeculectomy With Mitomycin C: A Prospective Randomized Placebo-controlled
      Trial.
AB  - PURPOSE: To evaluate the efficacy of subconjunctival bevacizumab (ScB) as
      adjuvant therapy to primary trabeculectomy with mitomycin C (MMC) in primary open
      angle glaucoma. MATERIALS AND METHODS: Forty-six eyes of primary open-angle
      glaucoma patients were randomized to receive ScB (1.25 mg/0.05 mL) injections
      (the MMC+ScB group) at the end of the operations, or sham-treated controls (the
      MMC group). Intraocular pressure (IOP) was the primary outcome and secondary
      outcomes included bleb appearance, visual acuity, number of medications,
      complications, and proportion of eyes achieving successful outcomes at the 12
      month follow-up. RESULTS: Of 39 eyes, 20 eyes from the MMC+ScB group, and 19 eyes
      from the MMC group completed the follow-up. The mean postoperative IOP was 15.5+/
      4.1 mm Hg in the MMC+ScB group (P<0.01; 40% reduction), and 14.7+/-4.3 mm Hg in
      the MMC group (P<0.01; 44% reduction). The differences in IOPs, at all follow-up
      visits, were not significant (P>0.05). The mean bleb vascularity score, at 1
      month, in the MMC+ScB group was lower than the MMC group (1.55+/-0.51 vs. 2.26+/
      0.6, respectively, P=0.01), but was not retained at follow-ups. The success rates
      at 12 months after surgery were 85% in the MMC+ScB group and 89.5% in the MMC
      group (P=0.53). The cumulative probabilities of surgical success were 80% and
      73.7% in the MMC+ScB and in the MMC group, respectively (P=0.52). CONCLUSION:
      Single adjunctive ScB injection did not appear to have an additive benefit on
      outcomes of MMC trabeculectomy, in terms of IOPs and success rates.

PMID- 25393040
TI  - Acute angle-closure glaucoma in a patient with miller fisher syndrome without
      pupillary dysfunction.
AB  - PURPOSE: To report a case of an angle-closure glaucoma in a patient with Miller
      Fisher syndrome (MFS) without pupillary dysfunction. METHODS: We present a case
      report of a 75-year-old male presenting with total ophthalmoplegia, complete
      bilateral ptosis, and gait disturbance. He was diagnosed with MFS without
      pupillary dysfunction, which precipitated unilateral acute angle-closure glaucoma
      (AACG) due to complete lid ptosis. RESULTS: The initial ocular examination
      revealed hand motion in the right eye. Intraocular pressure, as assessed by
      Goldmann applanation tonometry, was 50 mm Hg, and gonioscopic findings revealed a
      closed angle on the right eye. After maximal tolerated medical therapy, laser
      peripheral iridotomy was performed. The unilateral AACG with MFS resolved without
      further incident. CONCLUSIONS: This is the first reported case of a patient with
      MFS without autonomic dysfunction and AACG. We believe that pupillary dysfunction
      or lid ptosis due to neurological disorders may increase the possibility of AACG.

PMID- 25393042
TI  - Complementary surface second harmonic generation and molecular dynamics
      investigation of the orientation of organic dyes at a liquid/liquid interface.
AB  - The second-order nonlinear response of two dyes adsorbed at the dodecane/water
      interface was investigated by surface second harmonic generation (SSHG). These
      dyes consist of the same chromophoric unit, 2-pyridinyl-5-phenyloxazole, with an
      alkyl chain located at the two opposite ends. The analysis of the polarization
      dependence of the SSHG intensity as usually performed points to similar tilt
      angles of the two dyes with respect to the interface but does not give
      information on the absolute direction. Molecular dynamics (MD) simulations reveal
      that both dyes lie almost flat at the interface but have opposite orientations. A
      refined SSHG data analysis with the width of the orientational distribution
      yields tilt angles that are in very satisfactory agreement with the MD
      simulations. 

PMID- 25393041
TI  - Acetylation of Gly1 and Lys2 promotes aggregation of human gammaD-crystallin.
AB  - The human lens contains three major protein families: alpha-, beta-, and gamma
      crystallin. Among the several variants of gamma-crystallin in the human lens,
      gammaD-crystallin is a major form. gammaD-Crystallin is primarily present in the
      nuclear region of the lens and contains a single lysine residue at the second
      position (K2). In this study, we investigated the acetylation of K2 in gammaD
      crystallin in aging and cataractous human lenses. Our results indicated that K2
      is acetylated at an early age and that the amount of K2-acetylated gammaD
      crystallin increased with age. Mass spectrometric analysis revealed that in
      addition to K2, glycine 1 (G1) was acetylated in gammaD-crystallin from human
      lenses and in gammaD-crystallin acetylated in vitro. The chaperone ability of
      alpha-crystallin for acetylated gammaD-crystallin was lower than that for the
      nonacetylated protein. The tertiary structure and the microenvironment of the
      cysteine residues were significantly altered by acetylation. The acetylated
      protein exhibited higher surface hydrophobicity, was unstable against thermal and
      chemical denaturation, and exhibited a higher propensity to aggregate at 80 
      degrees C in comparison to the nonacetylated protein. Acetylation enhanced the
      GdnHCl-induced unfolding and slowed the subsequent refolding of gammaD
      crystallin. Theoretical analysis indicated that the acetylation of K2 and G1
      reduced the structural stability of the protein and brought the distal cysteine
      residues (C18 and C78) into close proximity. Collectively, these results indicate
      that the acetylation of G1 and K2 residues in gammaD-crystallin likely induced a
      molten globule-like structure, predisposing it to aggregation, which may account
      for the high content of aggregated proteins in the nucleus of aged and
      cataractous human lenses. 

PMID- 25393043
TI  - Alexithymia, Coping Styles and Traumatic Stress Symptoms in a Sample of Veterans
      Who Experienced Military Sexual Trauma.
AB  - The current study examined the association between alexithymia and coping styles
      (planning, positive reinterpretation and growth, social-emotion coping, and
      denial), and trauma symptoms in a clinical sample of 170 male and female veterans
      who experienced sexual trauma during military service. Denial was the only coping
      style positively associated with trauma symptoms, and it mediated the
      relationship between alexithymia and trauma symptoms. Alexithymia was negatively
      associated with planning. Likewise, alexithymia was negatively associated with
      social-emotional coping and with positive reinterpretation and growth. The
      results speak to the significant role that alexithymia has in predicting
      individual coping styles.

PMID- 25393044
TI  - Formation of an Endoperoxide upon Chromium-Catalyzed Allylic Oxidation of a
      Triterpene by Oxygen.
AB  - The chromium-catalyzed allylic oxidation of triterpene 1 with O2 and N
      hydroxyphthalimide (NHPI, 5 equiv) formed endoperoxide 2 in 76% yield at ambient
      temperature. Unlike standard allylic oxidations, this oxidation is catalytic in
      chromium because oxygen, not the chromium reagent, is the oxidant. This oxidation
      is sensitive to the precise structure of the substrate. The endoperoxide is only
      formed if ring A is unsaturated and ring C contains an enone. A mechanism is
      proposed that involves the coupling of two stabilized radicals on rings A and C
      to form endoperoxide 2. 

PMID- 25393045
TI  - High levels of CRP in morbid obesity: the central role of adipose tissue and
      lessons for clinical practice before and after bariatric surgery.
AB  - BACKGROUND: Obesity, characterized by low-grade inflammation both in blood and
      white adipose tissue (WAT) is associated with increased C-reactive protein (CRP),
      a well-known acute phase protein. The aim of this study was to determine factors
      associated with high levels of CRP in obesity. METHODS: In 674 obese patients
      candidates to bariatric surgery (mean body mass index [BMI]=47.4+/-7.4 kg/m2), we
      examined the relationships between CRP and a series of bioclinical markers and
      histologic features of subcutaneous and omental WAT (scWAT) and liver. We also
      compared the same parameters after separating patients with "high" inflammation
      (HI, CRP>=20 mg/L, n=52) and with "low" inflammation (LI, CRP<20 mg/L, n=622).
      RESULTS: Mean CRP was 8.9+/-6.9 mg/L and positively correlated with fat mass
      (P<10(-4)). The HI group included predominantly women (92% versus 79%), of a
      younger age, with higher BMI (50.9+/-8.8 versus 47.1+/-7.2 kg/m2, P=.003), and
      fat mass (51.6 versus 48.8%, P<.001), higher prevalence of obstructive sleep
      apnea (OSA) (73% versus 57%, P=.02), and had increased number of HAM56+ immune
      cells in scWAT (20.8 versus 14.5%, P=.05). There was no difference in metabolic
      status, WAT fibrosis or liver histology findings between the groups. After 1 year
      of surgery-induced weight loss, 48 out of 52 patients with HI returned to CRP
      levels<20 mg/L. CONCLUSION: Our results suggest that WAT inflammation is a major
      contributor to increased CRP in obesity. In obese patients presenting high CRP
      levels with no obvious explanation, age, gender, BMI, fat mass proportion, OSA,
      and WAT inflammation should be taken into account to decide to perform further
      additional medical investigations.

PMID- 25393046
TI  - Power-assisted liposuction (PAL) of multiple symmetric lipomatosis (MSL)--a
      longitudinal study.
AB  - BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare condition leading to
      grotesque disfigurement. Complete removal is almost impossible and recurrences
      inevitable. The objective of this study was to evaluate powered-assisted
      liposuction (PAL) for the treatment of MSL. METHODS: Magnetic resonance imaging
      (MRI) was performed before and after surgery for quality assessment. To exclude
      malignancy incisional biopsies were taken before surgery. Outcome measures
      included aspiration volumes, duration of surgery, early morbidity, recurrence
      rates, and overall patient satisfaction. RESULTS: Seven male patients aged
      between 43 and 70 years were identified. The mean liposuction volume equaled
      2948+/-1566 mL, the mean surgery time 74+/-28 minutes. One hematoma was observed,
      whereas 1 recurrence rate was noticed after a mean follow-up of 14 months.
      Malignancy was excluded by histology in 5 patients. Preoperative MRI confirmed
      the diagnosis with no signs for malignancy and showed an efficient removal of the
      lesions. After a mean follow-up of 18 months, a high patient satisfaction was
      achieved. CONCLUSION: PAL can serve as an efficient method for the treatment of
      MSL. It has a significant effect on tightening of the skin, leading to a high
      patient satisfaction.

PMID- 25393047
TI  - Short-term results of single-port sleeve gastrectomy in adolescents with severe
      obesity.
AB  - BACKGROUND: Dietary and lifestyle modifications, which are commonly proposed to
      overweight or obese youth, lack efficacy in individuals who are severely obese.
      Early results with bariatric procedures in obese adolescents suggest that weight
      loss and safety are comparable or better than seen in adults. One of these
      procedures, laparoscopic sleeve gastrectomy, is commonly performed using multiple
      ports. METHODS: We selected single-port sleeve gastrectomy (SPSG) as a minimally
      invasive surgery to be tested in severely obese adolescents. Prospective clinical
      and biochemical data were collected from 16 young severely obese patients who
      underwent SPSG. The setting was a university hospital. RESULTS: The mean age of
      the cohort was 17.8 years (12 girls, 4 boys). The individuals' average weight was
      125.5 kg and their average body mass index was 45.3 kg/m(2). All patients were
      insulin-resistant and 6 showed hypertriglyceridemia. The median operating time
      was 66 minutes, and there were no intraoperative complications. No conversion to
      open surgery was required. No patient required additional trocars and no patient
      had postoperative complications. The median hospital stay was 3 days. After a one
      year follow-up, the average weight decrease was 40.3 kg, resulting in a decrease
      in excess weight loss by 70.61%. Insulin-resistance decreased in 16/16 patients
      and hypertriglyceridemia decreased in 5/6 patients. CONCLUSION: SPSG seems safe
      and effective in the short term in severely obese adolescents.

PMID- 25393048
TI  - Revision LAGB to RYGBP in patients with BMI<35: not yet ready for prime time.

PMID- 25393050
TI  - Histology and ultrastructure of the caudal courtship glands of the red-backed
      salamander, Plethodon cinereus (Amphibia: Plethodontidae).
AB  - Caudal courtship glands (CCGs) are sexually dimorphic glands described in the
      skin of the dorsal tail base of some male salamanders in the genera Desmognathus,
      Eurycea, and Plethodon in the family Plethodontidae. These glands are believed to
      deliver pheromones to females during courtship, when the female rests her chin on
      the dorsal tail base during the stereotypic tail straddling walk unique to
      plethodontids. Although CCGs have been studied histologically, no investigations
      of their ultrastructure have been made. This article presents the first study on
      the fine structure and seasonal variation of CCGs, using the plethodontid
      Plethodon cinereus. The CCGs vary seasonally in height and secretory activity.
      The mature secretory granules observed in males collected in October and April
      consist of oval, biphasic granules that are eosinophilic and give positive
      reactions to periodic acid-Schiff for neutral carbohydrates but do not stain for
      acidic mucosusbtances or proteins with alcian blue and bromphenol blue,
      respectively. Granular glands, some of which contain mucous demilunes, are twice
      as large as CCGs, are syncytial (unlike CCGs), and stain for proteins. Mucous
      glands are similar in size to CCGs, but are basophilic, show no seasonal
      variation in secretory activity, and stain positive for acidic mucosubstances.
      CCGs do not resemble cytologically the sexually dimorphic mental glands of some
      plethodontids, which contain round or oval granules filled with an electron-dense
      amorphous substance. The CCGs are similar histologically to sexually dimorphic
      skin glands described in some anurans, but more comparative work is needed.

PMID- 25393049
TI  - Identification of muscarinic receptor subtypes involved in catecholamine
      secretion in adrenal medullary chromaffin cells by genetic deletion.
AB  - BACKGROUND AND PURPOSE: Activation of muscarinic receptors results in
      catecholamine secretion in adrenal chromaffin cells in many mammals, and
      muscarinic receptors partly mediate synaptic transmission from the splanchnic
      nerve, at least in guinea pigs. To elucidate the physiological functions of
      muscarinic receptors in chromaffin cells, it is necessary to identify the
      muscarinic receptor subtypes involved in excitation. EXPERIMENTAL APPROACH: To
      identify muscarinic receptors, pharmacological tools and strains of mice where
      one or several muscarinic receptor subtypes were genetically deleted were used.
      Cellular responses to muscarinic stimulation in isolated chromaffin cells were
      studied with the patch clamp technique and amperometry. KEY RESULTS: Muscarinic
      M1, M4 and M5 receptors were immunologically detected in mouse chromaffin cells,
      and these receptors disappeared after the appropriate gene deletion. Mouse cells
      secreted catecholamines in response to muscarinic agonists, angiotensin II and a
      decrease in external pH. Genetic deletion of M1, but not M3, M4 or M5, receptors
      in mice abolished secretion in response to muscarine, but not to other stimuli.
      The muscarine-induced secretion was suppressed by MT7, a snake peptide toxin
      specific for M1 receptors. Similarly, muscarine failed to induce an inward
      current in the presence of MT7 in mouse and rat chromaffin cells. The binding
      affinity of VU0255035 for the inhibition of muscarine-induced currents agreed
      with that for the M1 receptor. CONCLUSIONS AND IMPLICATIONS: Based upon the
      effects of genetic deletion of muscarinic receptors and MT7, it is concluded that
      the M1 receptor alone is responsible for muscarine-induced catecholamine
      secretion.

PMID- 25393051
TI  - Carbon dioxide insufflation vs conventional air insufflation for colonoscopy: a
      systematic review and meta-analysis of published randomized controlled trials.
AB  - AIM: Conventional air insufflation (AI) may cause prolonged abdominal bloating,
      excessive abdominal pain and discomfort during colonoscopy. Carbon dioxide may be
      an acceptable alternative to avoid these complications. The object of this study
      was to evaluate systematically the effectiveness of carbon dioxide insufflation
      (CI) for colonoscopy compared with AI. METHOD: Randomized controlled trials
      (RCTs) comparing the effectiveness of CI with that of AI during colonoscopy were
      retrieved from medical electronic databases and combined analysis was performed
      using the RevMan statistical package. The combined outcome of dichotomous and
      continuous variables was expressed as an odds ratio (OR) and standardized mean
      difference (SMD). RESULTS: Twenty-one RCTs comprising 3607 patients were included
      in the study. There was statistically significant heterogeneity among included
      studies. CI showed a significant trend towards reduced procedural pain [SMD 
      1.34; 95% confidence interval (95% CI) -2.23 to -0.45; z = 2.96; P < 0.003] and
      also postprocedural pain at 1 h (SMD -1.11; 95% CI -1.83 to -0.38; z = 2.97; P <
      0.003), 6 and 24 h (OR 0.44; 95% CI 0.23-0.85; z = 2.44; P < 0.01). CI was
      associated with faster caecal intubation (SMD -0.20; 95% CI -0.37 to -0.02; z =
      2.23; P < 0.03) but the caecal intubation rate was similar (P = 0.59) in both
      colonic insufflation techniques . CONCLUSION: CI seems to have clinical
      advantages over AI for colonoscopy with regard to pain during and after the
      procedure.

PMID- 25393052
TI  - Tunneling isomerization of small carboxylic acids and their complexes in solid
      matrixes: a computational insight.
AB  - We have studied hydrogen-atom tunneling in the cis-to-trans conformational change
      of some carboxylic acid monomers and formic acid (FA) complexes and dimers at the
      MP2(full) and CCSD(T) levels of theory within the Wentzel-Kramers-Brillouin
      approximation. The barrier for the minimum energy path, where the OH bond length
      and the COH bending angle are optimized, is found to be a good approximation for
      providing the highest barrier transparency. The matrix effect on the transmission
      coefficients of cis-FA monomer, trans-cis FA dimer (tc1), and cis-acetic acid
      monomer are modeled by the polarizable continuum model (PCM) at the MP2(full)
      level of theory in different environments. For the cis-FA monomer and trans-cis
      FA dimer (tc1), the calculated transmission coefficients agree with the
      experimental lifetimes observed in noble-gas solids. However, this method cannot
      reproduce the experimental results obtained for cis-acetic acid. Moreover, the
      long lifetime of cis-FA and cis-acetic acid in the N2 environment cannot be
      reproduced either, which is most probably due to specific interactions that are
      not included in the PCM. The calculation for cis-HCOOD shows a strong decrease of
      the barrier transparency compared to that for cis-HCOOH, which is consistent with
      the experiments. In general, good agreement is observed between the calculated
      barrier transparency (including PCM) and experimental tunneling rate. However,
      some exceptions are found, which shows that additional factors influence the
      tunneling rate. 

PMID- 25393053
TI  - RegionPlot: an R package for regional plot association results for pigs.

PMID- 25393054
TI  - Asian pacific digestive week, november 22, 2014, bali, indonesia.

PMID- 25393055
TI  - Ru-Zn heteropolynuclear complexes containing a dinucleating bridging ligand:
      synthesis, structure, and isomerism.
AB  - Mononuclear complexes in- and out-[Ru(Cl)(trpy)(Hbpp)](+) (in-0, out-0; Hbpp is
      2,2'-(1H-pyrazole-3,5-diyl)dipyridine and trpy is 2,2':6',2"-terpyridine) are
      used as starting materials for preparation of Ru-Zn heterodinuclear out
      {[Ru(Cl)(trpy)][ZnCl2](MU-bpp)} (out-2) and heterotrinuclear in,in- and out,out
      {[Ru(Cl)(trpy)]2(MU-[Zn(bpp)2])}(2+) (in-3, out-3) constitutional isomers.
      Further substitution of the Cl ligand from the former complexes leads to Ru-aqua
      out,out-{[Ru(trpy)(H2O)]2(MU-[Zn(bpp)2])}(4+) (out-4) and the oxo-bridged Ru-O-Ru
      complex in,in-{[Ru(III)(trpy)]2(MU-[Zn(bpp)2(H2O)]MU-(O)}(4+) (in-5). All
      complexes are thoroughly characterized by the usual analytical techniques as well
      as by spectroscopy by means of UV-vis, MS, and when diamagnetic NMR. CV and DPV
      are used to extract electrochemical information and monocrystal X-ray diffraction
      to characterize complexes out-2, in-3, out-3, and in-5 in the solid state.
      Complex out-3 photochemically isomerizes toward in-3, as can be observed by NMR
      spectroscopy and rationalized by density functional theory based calculations. 

PMID- 25393056
TI  - The polymorphic phase transformations in the chlorpropamide under pressure.
AB  - The crystal structure and vibrational spectra of the chlorpropamide have been
      studied by means of the X-ray diffraction and Raman spectroscopy at pressures up
      to 24.6 and 4.4 GPa, respectively. Two polymorphic phase transitions, between
      initial orthorhombic form-A and a monoclinic form-AI at P ~ 1.2 GPa and, in
      additional, to another monoclinic form-AII at P ~ 3.0 GPa, were observed. At
      pressures above 9.6 GPa, a transformation to the amorphous phase of
      chlorpropamide was revealed. The lattice parameters, unit cell volumes, and
      vibration modes as functions of pressure were obtained for the different
      polymorphic modifications of chlorpropamide.

PMID- 25393057
TI  - Arthroscopic Latarjet and Capsular Shift (ALCS) procedure: a new "freehand"
      technique for anterior shoulder instability associated with significant bone
      defects.
AB  - Anterior shoulder instability associated with significant bone loss has been
      described as "bony-instability," and this condition is usually treated with an
      anterior glenoid bone grafting procedure (Latarjet procedure). The Latarjet
      procedure involves transfer of the horizontal limb of the coracoid process along
      with the conjoint tendon to the anterior glenoid rim, and is traditionally
      performed as an open surgical procedure. Recently, an arthroscopic technique for
      the Latarjet procedure has been described; the technique necessitates the use of
      specialized instrumentation and involves excision of the entire anterior capsule
      to facilitate coracoid fixation. We describe a new "freehand" arthroscopic
      technique for the Latarjet procedure, and, in addition, a simultaneous capsular
      shift to further optimize mid and end range stability. This technique eliminates
      the use of additional instrumentation and can be done using routine arthroscopic
      instruments. Preliminary experience with this technique suggests that the
      arthroscopic Latarjet and capsular shift is a technically demanding procedure.
      Glenohumeral capsule can be preserved, and this should be attempted wherever
      possible to optimize stability. Additional specialized instrumentation would
      probably reduce surgical time; however, the procedure can be performed with
      routine instruments. 

PMID- 25393058
TI  - Clinical and radiographic changes after percutaneous endoscopic cervical
      discectomy: a long-term follow-up.
AB  - OBJECTIVE: Results following anterior cervical discectomy (ACD) without fusion
      are not well reported because of skepticism that the disturbed cervical spine
      anatomy after ACD might compromise clinical outcome. The purpose of this study
      was to determine whether ACD without fusion prompts the degenerative process
      significantly, and whether it is necessary to preserve disc height and cervical
      alignment for the sake of better clinical outcome following cervical spine
      surgery. BACKGROUND DATA: Out of 56 consecutive patients, 37 patients who replied
      and consequently underwent postoperative MRI from April to June 2009 were
      included in this study. MATERIAL AND METHODS: A total of 37 consecutive patients
      diagnosed as having cervical monoradiculopathy and treated with percutaneous
      endoscopic cervical discectomy (PECD) were investigated. Angle of cervical
      lordosis, change in cervical range of motion, disc height change, and degree of
      degenerative changes at the corresponding level were evaluated. The visual
      analogue scale (VAS) score for neck and arm pain and the neck disability index
      (NDI) were compared preoperatively and at the final follow-up. The mean follow-up
      period was 45.5 months. RESULTS: Despite prompted radiological deterioration such
      as loss of disc height (the posterior disc heights and central disc height ratio
      were significantly decreased from 3.6 to 2.6 mm, from 30.3% to 24.5%,
      respectively, p<0.05) or degenerative progression (from average grade of 2.8 to
      4.1, p<0.05), the patients achieved significant improvement in clinical outcomes
      (VAS for neck and arm dropped from mean 6.3 and 7.5 to 2.7 and 2.6, respectively,
      and NDI score improved from 46.8% to 17.2%, p<0.05) after PECD. CONCLUSIONS:
      Neither loss of disc height nor progression of degeneration at disc space
      compromised clinical outcome after PECD without fusion on long-term follow-up.

PMID- 25393060
TI  - Detection and quantification of chloramphenicol in milk and honey using
      molecularly imprinted polymers: Canadian penny-based SERS nano-biosensor.
AB  - We integrated molecularly imprinted polymers with surface-enhanced Raman
      spectroscopy (MIPs-SERS) to develop an innovative nano-biosensor for the
      determination of chloramphenicol (CAP) in milk and honey products. Template
      molecule (CAP), functional monomer (acrylamide), cross-linking agent (ethylene
      glycol dimethacrylate), initiator (2,2'-azobis(isobutyronitrile)), and porogen
      (methanol) were employed to form MIPs via "dummy" precipitation polymerization.
      Static and kinetic studies validated the specific selectivity of MIPs toward CAP
      over nonimprinted polymers (imprinting factor >4). Canadian penny-based silver
      nano-structure was synthesized as SERS-active substrate for determination of CAP
      in food matrices. Collected spectra were processed by principal component
      analysis to differentiate various concentrations of CAP in foods. Partial least
      squares regression models showed good prediction values (R > 0.9) of actual
      spiked contents (0, 0.1, 0.5, 1, 5 ppm) of CAP in milk and honey. This developed
      nano-biosensor is low cost, requires little sample pretreatment, and can provide
      reliable detection of trace level of chemical hazards in food systems within a
      total of 15 min. 

PMID- 25393059
TI  - Effectiveness of a new navigable percutaneous disc decompression device (L'DISQ)
      in patients with lumbar discogenic pain.
AB  - OBJECTIVE: This study is a pilot study to assess the clinical outcomes of
      percutaneous disc decompression using the L'DISQ in patients with lumbar
      discogenic pain. STUDY DESIGN: An institutional, prospective clinical data
      analysis. METHODS: We ablated the torn annulus using L'DISQ on 20 patients with
      axial low back pain for at least 3 months (average 29 months) unresponsive to
      conservative management. Before the therapeutic procedure, all the patients had
      been diagnosed with lumbar discogenic pain through provocation discography, which
      had confirmed the level of painful discs. The torn annulus was identified through
      lumbosacral magnetic resonance image and computed tomographic discogram. Baseline
      data were prospectively gathered before the procedure and at 1, 4, 12, 24, and 48
      weeks post-procedure. Data included pain intensity (visual analog scale [VAS]),
      measure of disability (Oswestry Disability Index [ODI] and Rolando-Morris
      Disability Questionnaire [RM]), and health-related quality of life (Bodily Pain
      Scale of Short Form-36 version 2 [SF-36 BP]). RESULTS: At 48 weeks, the VAS fell
      from 7.55 +/- 1.28 to 3.60 +/- 2.28 scores, the ODI and RM had decreased
      significantly, and the SF-36 BP showed significant improvement (P < 0.05). The
      success rates of procedure were 55.0% at 48 weeks. There were no complications
      with the exception of a minor venous bleeding at the site of needle puncture.
      CONCLUSIONS: The L'DISQ device is specifically designed to ablate adjacent disc
      tissue using a wand that can be navigated into a torn annulus. Following
      ablation, we measured clinically significant pain improvement and decreased
      disability for patients with axial low back pain.

PMID- 25393061
TI  - Recent developments in neurofibromatoses and RASopathies: management, diagnosis
      and current and future therapeutic avenues.
AB  - Neurofibromatosis type 1 (NF1) was the first RASopathy and is now one of many
      RASopathies that are caused by germline mutations in genes that encode components
      of the Ras/mitogen-activated protein kinase (MAPK) pathway. Their common
      underlying pathogenetic etiology causes significant overlap in phenotypic
      features which includes craniofacial dysmorphology, cardiac, cutaneous,
      musculoskeletal, GI and ocular abnormalities, and a predisposition to cancer. The
      proceedings from the symposium "Recent Developments in Neurofibromatoses (NF) and
      RASopathies: Management, Diagnosis and Current and Future Therapeutic Avenues"
      chronicle this timely and topical clinical translational research symposium. The
      overarching goal was to bring together clinicians, basic scientists, physician
      scientists, advocate leaders, trainees, students and individuals with Ras pathway
      syndromes to discuss the most state-of-the-art basic science and clinical issues
      in an effort to spark collaborations directed towards the best practices and
      therapies for individuals with RASopathies.

PMID- 25393062
TI  - Interventional pulmonology: the tipping point.

PMID- 25393064
TI  - Topographically-designed triboelectric nanogenerator via block copolymer self
      assembly.
AB  - Herein, we report a facile and robust route to nanoscale tunable triboelectric
      energy harvesters realized by the formation of highly functional and controllable
      nanostructures via block copolymer (BCP) self-assembly. Our strategy is based on
      the incorporation of various silica nanostructures derived from the self-assembly
      of BCPs to enhance the characteristics of triboelectric nanogenerators (TENGs) by
      modulating the contact-surface area and the frictional force. Our simulation data
      also confirm that the nanoarchitectured morphologies are effective for
      triboelectric generation. 

PMID- 25393063
TI  - Structure-Based Design and Synthesis of a Small Molecule that Exhibits Anti
      inflammatory Activity by Inhibition of MyD88-mediated Signaling to Bacterial
      Toxin Exposure.
AB  - Both Gram-positive and Gram-negative pathogens or pathogen-derived components,
      such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate
      MyD88-mediated pro-inflammatory cellular immunity for host defense. However,
      dysregulated MyD88-mediated signaling triggers exaggerated immune response that
      often leads to toxic shock and death. Previously, we reported a small molecule
      compound 1 mimicking BB-loop structure of MyD88 was capable of inhibiting pro
      inflammatory response to SEB exposure in mice. In this study, we designed a
      dimeric structure compound 4210 covalently linked with compound 1 by a non-polar
      cyclohexane linker which strongly inhibited the production of pro-inflammatory
      cytokines in human primary cells to SEB (IC50 1-50 MUm) or LPS extracted from
      Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC50 10-200
      MUm). Consistent with cytokine inhibition, in a ligand-induced cell-based
      reporter assay, compound 4210 inhibited Burkholderia mallei or LPS-induced MyD88
      mediated NF-kB-dependent expression of reporter activity (IC50 10-30 MUm).
      Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited
      MyD88 dimer formation which is critical for pro-inflammatory signaling.
      Importantly, a single administration of compound 4210 in mice showed complete
      protection from lethal toxin challenge. Collectively, these results demonstrated
      that compound 4210 inhibits toxin-induced inflated pro-inflammatory immune
      signaling, thus displays a potential bacterial toxin therapeutic. 

PMID- 25393065
TI  - Endoscopic endonasal resection of respiratory epithelial adenomatoid hamartomas
      of the sinonasal tract.
AB  - BACKGROUND: Respiratory epithelial adenomatoid hamartomas (REAHs) are rare benign
      tumors and may manifest as either isolated lesions or in association with
      sinonasal polyposis. The aim of this study is to report our experience in the
      management of patients with REAH and to analyze the long-term results of the
      endoscopic endonasal approach. METHODS: A retrospective analysis of a database
      dedicated to patients with REAH treated between May 2003 and December 2012 was
      performed. Clinical presentation, demographic, histologic and radiographic
      features, operative findings, and follow-up data were examined. RESULTS: Twenty
      seven patients with REAH, 14 males and 13 females, with a mean age of 51 years,
      underwent endoscopic sinus surgery (ESS). The most frequent reported symptoms
      were nasal obstruction (80%), headache (12%), mucous rhinorrhea (20%), and
      hyposmia (40%). Seventeen cases (first group) were present as isolated masses, 10
      cases (second group) were associated with nasal polyposis. The first group with a
      preoperative diagnosis of REAH was submitted to a more aggressive resection with
      subperiosteal dissection and drilling of the underlying bone. The patients in the
      second group, because of the unrevealed diagnosis of REAH and due to the presence
      of nasal polyposis, underwent standard ESS. No evidence of recurrence in either
      of the subgroups after a mean follow-up of 61.2 months. CONCLUSION: REAH is a
      benign well-defined pathological entity but is still unfamiliar. REAH should be
      kept in mind as a differential diagnosis from more aggressive lesions to avoid
      unnecessary surgical procedure. A complete but conservative endoscopic resection
      appears to be curative.

PMID- 25393071
TI  - 3 T MRI-based measurements for the integrity of the female pelvic floor in 25
      healthy nulliparous women.
AB  - AIMS: Measurements indicating a loss of integrity of the levator ani muscle,
      which is an integral part of the pelvic floor, have been subject of recent
      studies using translabial ultrasound and 3D-MRI-models. We transferred these
      measurements into 2D-3 T-MR-images for clinical routine, as it is objective and
      does not need exhaustive post-processing. METHODS: The trial was accepted by the
      local ethics committee. 25 healthy volunteers fulfilled the inclusion criteria
      and gave written informed consent. Using high-resolution T2-weighted images (TE
      5030-7810 ms, TR 88-112 ms, matrix 512, FOV 280-300 mm, ST 2-3 mm), measurements
      of anteroposterior hiatus (APH), laterolateral hiatus (LLH), hiatal area (HA),
      hiatal circumference (HC), levator area (LA), maximum muscle thickness (MMT) and
      levator urethra gap (LUG) were transferred from ultrasound, iliococcygeus width
      (IW), puborectalis attachment width (PAW), and levator symphysis gap (LSG) were
      transferred from 3D-MRI-models. We compared our results to previous studies in
      the literature. RESULTS: Mean value was 52.22 +/- 6.97 mm for APH, 33.15 +/- 4 mm
      for LLH, 13.22 +/- 3.05 cm(2) for HA, 14.19 +/- 1.61 cm for HC, 7.14 +/- 1.85
      cm(2) for LA, 6.45 +/- 2.07 mm for MMT, 19.47 +/- 2.38 mm for LUG, 45 +/- 3.97 mm
      for IW, 33.94 +/- 3.34 mm for PAW, 20.54 +/- 5.29 mm for LSG. Our results for
      APH, HA, LUG, and with limitations LA, were comparable to the literature, while
      HC, LLH, and MMT showed anatomical variances. Results for IW and LSG were
      comparable, but challenging to measure. We newly proposed a cutoff value for PAW.
      CONCLUSIONS: 2D-3 T-MRI combines high-resolution images with objective
      measurements of parameters regarding pelvic floor integrity, without resorting to
      exhaustive post-processing methods. Our results may provide a good foundation for
      further 2D-MR-studies.

PMID- 25393072
TI  - Nabumetone and 6-MNA Pharmacokinetics, Assessment of Intrasubject Variability and
      Gender Effect.
AB  - In this open-label, laboratory-blinded, 2-way single dose study in 24 volunteers
      of both sexes we found that (1) nabumetone reaches mean Cmax +/- SD of 0.56 +/-
      0.20 mg.L at mean tmax of 8.63 +/- 7.05 hours, and mean area under the curve
      (AUC)last of 18.07 +/- 7.19 h.mg.L; (2) there are no statistically significant
      differences between both sexes in pharmacokinetics of nabumetone; (3) 6-methoxy-2
      naphthylacetic acid (6-MNA) reaches higher AUClast in men compared with women
      (mean +/- SD, 721.23 +/- 185.53 h.mg.L and 545.27 +/- 97.69 h.mg.L, respectively;
      P = 0.013); (4) there is lower 6-MNA clearance in men (0.65 +/- 0.22 L.h) in
      comparison with women (0.88 +/- 0.18 L.h, P = 0.019), (5) intersubject
      variability of nabumetone and 6-MNA is between 35%-45% and 10%-30% for all
      assessed pharmacokinetics parameters (AUClast, Cmax, partial AUC values); (6)
      intrasubject variability (ISCV) for AUClast is low, 15.59% and 6.40% for
      nabumetone and 6-MNA, respectively, (7) ISCV for Cmax is 13.66% and 5.42% for
      nabumetone and 6-MNA, respectively. Nabumetone thus belongs to compounds with low
      to moderate ISCV and therefore this product is expected to produce consistent
      effects in clinical practice.

PMID- 25393073
TI  - Haloperidol, a Novel Treatment for Cannabinoid Hyperemesis Syndrome.
AB  - Cannabinoid hyperemesis syndrome (CHS) is typically unresponsive to conventional
      pharmacologic antiemetics, and patients often require excessive laboratory and
      radiographic testing and hospital admission. We report 4 cases of CHS that failed
      standard emergency department therapy but improved significantly after treatment
      with haloperidol. Although the exact mechanism for CHS remains unclear,
      dysregulation at cannabinoid type 1 seems to play a role. Recent animal data
      demonstrate complex interactions between dopamine and cannabinoid type 1
      signaling, a potential mechanism for haloperidol success in patients with CHS.
      Our success with haloperidol in these 4 patients warrants further investigation
      of haloperidol as an emergency department treatment for CHS.

PMID- 25393074
TI  - Using distributed temperature sensing for hydrogeological studies in China.

PMID- 25393075
TI  - Portal vein patency after pancreatoduodenectomy for periampullary cancer.
AB  - BACKGROUND: The fate of the portal vein (PV) after pancreatoduodenectomy,
      especially its long-term patency and associated complications, has received
      little attention. The aim of this study was to explore the long-term patency rate
      of the PV after pancreatoduodenectomy, focusing on risk factors for PV
      stenosis/occlusion and associated complications. METHODS: Serial CT images of
      patients who underwent pancreatoduodenectomy for periampullary cancer between
      January 2000 and June 2012 in a single institution were evaluated for PV stenosis
      or occlusion. RESULTS: A total of 826 patients were enrolled. The PV
      stenosis/occlusion rate after pancreatoduodenectomy was 19.6 per cent and the 5
      year patency rate 69.9 per cent. The most frequent cause of PV stenosis/occlusion
      was local recurrence followed by postoperative change and PV thrombosis. Patients
      who underwent PV resection had a higher PV stenosis/occlusion rate than those who
      did not (51 versus 17.4 per cent; P < 0.001). The 3-year patency rate was highest
      in patients with cancer of the ampulla of Vater and lowest in patients with
      pancreatic cancer (91.9 versus 55.5 per cent respectively; P < 0.001).
      Multivariable analysis showed that risk factors for PV stenosis/occlusion
      included primary tumour location, chemoradiotherapy and PV resection. PV stenosis
      or occlusion without disease recurrence was observed in 17.3 per cent of the
      patients. PV resection and grade B or C pancreatic fistula were independent risk
      factors for PV stenosis/occlusion. Among 162 patients with PV stenosis or
      occlusion, five (3.1 per cent) had fatal recurrent gastrointestinal bleeding.
      CONCLUSION: PV stenosis or occlusion is common after pancreatoduodenectomy,
      particularly if the PV has been resected and/or chemoradiotherapy was given after
      surgery. Although recurrence is the most frequent cause of PV stenosis/occlusion,
      this complication is found in a significant proportion of patients without
      disease recurrence.

PMID- 25393076
TI  - Accuracy of first-trimester ultrasound in diagnosis of intrauterine pregnancy
      prior to visualization of the yolk sac: a systematic review and meta-analysis.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of ultrasound in predicting the
      location of an intrauterine pregnancy before visualization of the yolk sac is
      possible. METHODS: This was a systematic review conducted in accordance with the
      PRISMA statement and registered with PROSPERO. We searched MEDLINE, EMBASE and
      The Cochrane Library for relevant citations. Studies were selected in a two-stage
      process and their data extracted by two reviewers. Accuracy measures were
      calculated for each ultrasound sign, i.e. gestational sac, double decidual sac
      sign, intradecidual sign, chorionic rim sign and yolk sac. Individual study
      estimates were plotted in summary receiver-operating characteristics curves and
      forest plots for examination of heterogeneity. The quality of included studies
      was assessed. RESULTS: Seventeen studies including 2564 women were selected from
      19 959 potential papers. Following meta-analysis, the presence of a gestational
      sac on ultrasound examination was found to predict an intrauterine pregnancy with
      a sensitivity of 52.8% (95% CI, 38.2-66.9%) and specificity of 97.6% (95% CI,
      94.3-99.0%). The corresponding performance of the double decidual sac sign,
      intradecidual sign, chorionic rim sign and yolk sac were: 81.8% (95% CI, 68.1
      90.4%) and 97.3% (95% CI, 76.1-99.8%); 66.1% (95% CI, 58.9-72.8%) and 100% (95%
      CI, 91.0-100%); 79.9% (95% CI, 73.0-85.7%) and 97.1% (95% CI, 89.9-99.6%); and
      42.2% (95% CI, 27.7-57.9%) and 100% (95% CI, 54.1-100%), respectively.
      CONCLUSION: Visualization of a gestational sac, double decidual sac sign,
      intradecidual sign or chorionic rim sign increases the probability of an
      intrauterine pregnancy but is not as accurate for diagnosis as the detection of
      the yolk sac. However, the findings were limited by the small number and poor
      quality of the studies included and heterogeneity in the index test and reference
      standard.

PMID- 25393078
TI  - Solution structure of a bacterial immunoglobulin-like domain of the outer
      membrane protein (LigB) from Leptospira.
AB  - Leptospiral immunoglobulin-like (Lig) proteins are surface proteins expressed in
      pathogenic strains of Leptospira. LigB, an outer membrane protein containing
      tandem repeats of bacterial Ig-like (Big) domains and a no-repeat tail, has been
      identified as a virulence factor involved in adhesion of pathogenic Leptospira
      interrogans to host cells. A Big domain of LigB, LigBCen2R, was reported
      previously to bind the GBD domain of fibronectin, suggesting its important role
      in leptospiral infections. In this study, we determined the solution structure of
      LigBCen2R by nuclear magnetic resonance (NMR) spectroscopy. LigBCen2R adopts a
      canonical immunoglobulin-like fold which is comprised of a beta-sandwich of ten
      strands in three sheets. We indicated that LigBCen2R is able to bind to Ca(2+)
      with a high affinity by isothermal titration calorimetry assay. NMR perturbation
      experiment identified a number of residues responsible for Ca(2+) binding.
      Structural comparison of it with other Big domains demonstrates that they share a
      similar fold pattern, but vary in some structural characters. Since Lig proteins
      play a vital role in the infection to host cells, our study will contribute a
      structural basis to understand the interactions between Leptospira and host
      cells.

PMID- 25393079
TI  - Effects of luteinizing hormone receptor signaling in prostate cancer cells.
AB  - BACKGROUND: The importance of androgen signaling in prostate cancer (PC) is well
      described and prostate cancer cells retain the ability to directly synthesize
      androgens. Luteinizing hormone (LH) can induce expression of steroidogenic
      enzymes and trigger androgen production, but the regulation of this process is
      not well-described. Here, we explored the impact of silencing LH receptor (LHR)
      silencing on androgen synthesis and on several relevant signaling pathways in PC.
      METHODS: LHR mRNA and protein expression was evaluated in LNCaP PC cells treated
      with LHR-siRNA. MTS assay was used to measure the effect of LHR-siRNA on
      proliferation in LNCaP and 22RV1 PC cells. Treated LNCaP and LAPC-3 cells were
      also assayed for differences in androgen synthesis and expression of
      steroidogenic enzymes, PSA, AR, and critical signaling molecules including PKA,
      ERK1/2, PI3K, AKT2, and HER2. RESULTS: We confirmed that functional LHR is
      expressed in both androgen-sensitive and castrate-resistant PC specimens.
      Treatment with LHR-siRNA effectively silenced LHR gene and protein expression and
      prevented LH-mediated proliferation and androgen synthesis in prostate cancer
      cells. LHR silencing also downregulated expression of AR, PSA, PKA, ERK1/2, PI3K,
      AKT2, and HER2. CONCLUSION: Collectively, these data demonstrate that silencing
      LHR expression suppresses androgen synthesis and signaling and the LH-LHR pathway
      may represent a viable therapeutic strategy in PC.

PMID- 25393077
TI  - New charge-bearing amino acid residues that promote beta-sheet secondary
      structure.
AB  - Proteinogenic amino acid residues that promote beta-sheet secondary structure are
      hydrophobic (e.g., Ile or Val) or only moderately polar (e.g., Thr). The design
      of peptides intended to display beta-sheet secondary structure in water typically
      requires one set of residues to ensure conformational stability and an orthogonal
      set, with charged side chains, to ensure aqueous solubility and discourage self
      association. Here we describe new amino acids that manifest substantial beta
      sheet propensity, by virtue of beta-branching, and also bear an ionizable group
      in the side chain. 

PMID- 25393082
TI  - Response.

PMID- 25393080
TI  - Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled
      pilot study.
AB  - OBJECTIVE: Melatonin has been shown to be neuroprotective in animal models. The
      objective of this study is to examine the effect of melatonin on clinical,
      biochemical, neurophysiological and radiological outcomes of neonates with
      hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We conducted a prospective
      trial on 45 newborns, 30 with HIE and 15 healthy controls. HIE infants were
      randomized into: hypothermia group (N=15; received 72-h whole-body cooling) and
      melatonin/hypothermia group (N=15; received hypothermia and five daily enteral
      doses of melatonin 10 mg kg(-1)). Serum melatonin, plasma superoxide dismutase
      (SOD) and serum nitric oxide (NO) were measured at enrollment for all infants
      (N=45) and at 5 days for the HIE groups (N=30). In addition to
      electroencephalography (EEG) at enrollment, all surviving HIE infants were
      studied with brain magnetic resonance imaging (MRI) and repeated EEG at 2 weeks
      of life. Neurologic evaluations and Denver Developmental Screening Test II were
      performed at 6 months. RESULT: Compared with healthy neonates, the two HIE groups
      had increased melatonin, SOD and NO. At enrollment, the two HIE groups did not
      differ in clinical, laboratory or EEG findings. At 5 days, the
      melatonin/hypothermia group had greater increase in melatonin (P<0.001) and
      decline in NO (P<0.001), but less decline in SOD (P=0.004). The
      melatonin/hypothermia group had fewer seizures on follow-up EEG and less white
      matter abnormalities on MRI. At 6 months, the melatonin/hypothermia group had
      improved survival without neurological or developmental abnormalities (P<0.001).
      CONCLUSION: Early administration of melatonin to asphyxiated term neonates is
      feasible and may ameliorate brain injury.

PMID- 25393081
TI  - Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report
      from the Children's Hospitals Neonatal Consortium HIE focus group.
AB  - OBJECTIVE: To characterize infants affected with perinatal hypoxic ischemic
      encephalopathy (HIE) who were referred to regional neonatal intensive care units
      (NICUs) and their related short-term outcomes. STUDY DESIGN: This is a
      descriptive study evaluating the data collected prospectively in the Children's
      Hospital Neonatal Database, comprised of 27 regional NICUs within their
      associated children's hospitals. A consecutive sample of 945 referred infants
      born ?36 weeks' gestation with perinatal HIE in the first 3 days of life over
      approximately 3 years (2010-July 2013) were included. Maternal and infant
      characteristics are described. Short-term outcomes were evaluated including
      medical comorbidities, mortality and status of survivors at discharge. RESULT:
      High relative frequencies of maternal predisposing conditions, cesarean and
      operative vaginal deliveries were observed. Low Apgar scores, profound metabolic
      acidosis, extensive resuscitation in the delivery room, clinical and
      electroencephalographic (EEG) seizures, abnormal EEG background and brain imaging
      directly correlated with the severity of HIE. Therapeutic hypothermia was
      provided to 85% of infants, 15% of whom were classified as having mild HIE.
      Electrographic seizures were observed in 26% of the infants. Rates of
      complications and morbidities were similar to those reported in prior clinical
      trials and overall mortality was 15%. CONCLUSION: Within this large contemporary
      cohort of newborns with perinatal HIE, the application of therapeutic hypothermia
      and associated neurodiagnostic studies appear to have expanded relative to
      reported clinical trials. Although seizure incidence and mortality were lower
      compared with those reported in the trials, it is unclear whether this
      represented improved outcomes or therapeutic drift with the treatment of milder
      disease.

PMID- 25393083
TI  - PLA2G2A overexpression is associated with poor therapeutic response and inferior
      outcome in rectal cancer patients receiving neoadjuvant concurrent
      chemoradiotherapy.
AB  - AIMS: The aim of this study was to investigate the prognostic impact of group IIA
      phospholipase A2 (PLA2G2A) expression and its role in predicting the response to
      neoadjuvant concurrent cheomoradiotherapy (CCRT) in rectal cancer. METHODS AND
      RESULTS: Through analysing a public transcriptome of rectal cancers, the PLA2G2A
      gene was identified as a significant predictor for CCRT response. We validated
      the expression of PLA2G2A using immunohistochemistry in the pretreatment tumour
      specimens from 172 patients with rectal cancer. The results were correlated with
      clinicopathological features, tumour regression grade, overall survival (OS),
      disease-free survival (DFS) and local recurrence-free survival (LRFS). High
      expression of PLA2G2A was associated with advanced pretreatment tumour status (P
      = 0.001), advanced pretreatment nodal status (P = 0.010), advanced post-treatment
      tumour status (P = 0.002) and lower tumour regression grade (P = 0.006).
      Furthermore, PLA2G2A expression was correlated negatively with gamma H2A histone
      family, member X (gamma-H2AX) expression (P < 0.001, r = -0.580). More
      importantly, high expression of PLA2G2A emerged as an adverse prognostic factor
      for OS (P = 0.0190), DFS (P < 0.0001) and LRFS (P < 0.0001). In multivariate
      analysis, it remained independently prognostic for shorter DFS (P = 0.014) and
      LRFS (P = 0.012). CONCLUSIONS: High expression of PLA2G2A was associated with
      poor therapeutic response and worse survival in patients with rectal cancer
      receiving neoadjuvant CCRT, justifying PLA2G2A as an important marker to predict
      CCRT response and outcome.

PMID- 25393084
TI  - A case of sarcoidosis mimicking recurrences of endometrial cancer.

PMID- 25393085
TI  - Nature of the water/aromatic parallel alignment interactions.
AB  - The water/aromatic parallel alignment interactions are interactions where the
      water molecule or one of its O-H bonds is parallel to the aromatic ring plane.
      The calculated energies of the interactions are significant, up to
      DeltaE(CCSD)(T)(limit) = -2.45 kcal mol(-1) at large horizontal displacement, out
      of benzene ring and CH bond region. These interactions are stronger than CH...O
      water/benzene interactions, but weaker than OH...pi interactions. To investigate
      the nature of water/aromatic parallel alignment interactions, energy
      decomposition methods, symmetry-adapted perturbation theory, and extended
      transition state-natural orbitals for chemical valence (NOCV), were used. The
      calculations have shown that, for the complexes at large horizontal
      displacements, major contribution to interaction energy comes from electrostatic
      interactions between monomers, and for the complexes at small horizontal
      displacements, dispersion interactions are dominant binding force. The NOCV-based
      analysis has shown that in structures with strong interaction energies charge
      transfer of the type pi -> sigma*(O-H) between the monomers also exists.

PMID- 25393086
TI  - A 9-year, bidirectional prospective analysis of depressive symptoms and
      adiposity: the African American Health Study.
AB  - OBJECTIVE: Depression may be a predictor and consequence of obesity. However,
      available evidence for racial minorities has been inconsistent, and more
      prospective studies are needed. Thus, this study's objective was to examine
      whether depressive symptom severity is a predictor and/or consequence of total
      adiposity over a 9-year period in a representative sample of late middle-aged
      African-Americans. METHODS: A total of 410 participants (aged 49-65 years;
      baseline) in the prospective cohort African American Health study were examined.
      Depressive symptom severity was assessed with the Center for Epidemiologic
      Studies-Depression Scale (CES-D). Total body fat percent (BF%) and body mass
      index (BMI; kg/m(2) ) were assessed. Structural equation models were tested.
      RESULTS: All model fit statistics, other than chi(2) , indicated good fit (RMSEA
      <= 0.058, SRMR <= 0.052, CFI >= 0.95). Baseline CES-D did not predict 9-year
      changes in BF% (beta = -0.01, P = 0.78) or BMI (beta = -0.01, P = 0.77). Baseline
      BF% (beta = 0.05, P = 0.39) and BMI (beta = 0.08, P = 0.095) did not predict 9
      year change in CES-D. CONCLUSIONS: Depressive symptom severity was not a
      predictor or consequence of excess total adiposity in late middle-aged African
      American adults. Including a depression module in obesity prevention and
      treatment programs specifically designed for late middle-aged African-Americans
      may not have a beneficial effect on obesity outcomes.

PMID- 25393087
TI  - Detailed structure-function correlations of Bacillus subtilis acetolactate
      synthase.
AB  - Isobutanol is deemed to be a next-generation biofuel and a renewable platform
      chemical.1 Non-natural biosynthetic pathways for isobutanol production have been
      implemented in cell-based and in vitro systems with Bacillus subtilis
      acetolactate synthase (AlsS) as key biocatalyst.2-6 AlsS catalyzes the
      condensation of two pyruvate molecules to acetolactate with thiamine diphosphate
      and Mg(2+) as cofactors. AlsS also catalyzes the conversion of 2-ketoisovalerate
      into isobutyraldehyde, the immediate precursor of isobutanol. Our phylogenetic
      analysis suggests that the ALS enzyme family forms a distinct subgroup of ThDP
      dependent enzymes. To unravel catalytically relevant structure-function
      relationships, we solved the AlsS crystal structure at 2.3 A in the presence of
      ThDP, Mg(2+) and in a transition state with a 2-lactyl moiety bound to ThDP. We
      supplemented our structural data by point mutations in the active site to
      identify catalytically important residues. 

PMID- 25393088
TI  - The role of ability, motivation, and opportunity to work in the transition from
      work to early retirement--testing and optimizing the Early Retirement Model.
AB  - OBJECTIVES: Determinants in the domains health, job characteristics, skills, and
      social and financial factors may influence early retirement through three central
      explanatory variables, namely, the ability, motivation, and opportunity to work.
      Based on the literature, we created the Early Retirement Model. This study aims
      to investigate whether data support the model and how it could be improved.
      METHODS: Employees aged 58-62 years (N=1862), who participated in the first three
      waves of the Dutch Study on Transitions in Employment, Ability and Motivation
      (STREAM) were included. Determinants were assessed at baseline, central
      explanatory variables after one year, and early retirement after two years.
      Structural equation modeling was applied. RESULTS: Testing the Early Retirement
      Model resulted in a model with good fit. Health, job characteristics, skills, and
      social and financial factors were related to the ability, motivation and/or
      opportunity to work (significant beta range: 0.05-0.31). Lower work ability
      (beta=-0.13) and less opportunity to work (attitude colleagues and supervisor
      about working until age 65: beta=-0.24) predicted early retirement, whereas the
      motivation to work (work engagement) did not. The model could be improved by
      adding direct effects of three determinants on early retirement, ie, support of
      colleagues and supervisor (beta=0.14), positive attitude of the partner with
      respect to early retirement (beta=0.15), and not having a partner (beta=-0.13).
      CONCLUSIONS: The Early Retirement Model was largely supported by the data but
      could be improved. The prolongation of working life might be promoted by work
      related interventions focusing on health, work ability, the social work climate,
      social norms on prolonged careers, and the learning environment.

PMID- 25393089
TI  - A comparative randomized study on the efficacy of a systemic steroid therapy vs.
      a thermal therapy in otitis media with effusion in children.
AB  - BACKGROUND: The aim of this study was to compare the effectiveness of a systemic
      steroid therapy vs. a thermal therapy based on sulphurous water insufflation. The
      therapy was performed in Telese Terme Spa based on the Salimbani-Politzer
      technique on children suffering of otitis media with effusion (OME), using the
      variations of the tympanogram as objective outcome in a short time follow-up.
      METHODS: Eighty children suffering of monolateral or bilateral OME (44 male, 36
      female, age 4-12 years, average age 7.2+/-2.83 ys.), enrolled in ENT or
      paediatrics offices, have been included in the study. Children were included in a
      randomization list in order to obtain two therapeutic groups, the first one to be
      treated through a systemic steroid therapy, the second one to be treated through
      sulphuruos water insufflation in Telese Spa. Children underwent
      otoscopic/otomicroscopic visit and tympanometry before the beginning of the
      therapy (T0), 7 days after the beginning of the therapy (T1), 7-10 days after the
      end of the therapy (T2), 30-35 days after the end of the therapy (T3). The
      variation of the type of tympanogram was considered the objective outcome. The
      shift either from a type B to a type C or o type A tympanogram and from a type C
      to a type A tympanogram was considered a positive outcome; the persistence either
      of the same type of tympanogram and the shift from a type C to a type B or from a
      type A to a type C or a type B were considered a negative outcome. RESULTS:
      Thermal therapy showed better outcomes at each time, with differences in
      improvement and healing often reaching the statistical significance. The most
      important prognostic indicator was the presence of an initial type B tympanogram,
      associated to a worst prognosis in both therapeutic groups and in each subgroup
      of OME. CONCLUSIONS: Sulphurous water insufflation therapy appeared a good
      therapeutic choose in the treatment of OME in a pediatric population.

PMID- 25393090
TI  - Combination topical therapy for conjunctival primary acquired melanosis with
      atypia and periocular lentigo maligna.
AB  - PURPOSE: To report the case of a patient who initially presented with primary
      acquired melanosis (PAM) without atypia of the conjunctiva and later developed
      lentigo maligna of the eyelids and PAM with atypia of the conjunctiva. We
      illustrate the utility of combination topical therapy with adjunctive cryotherapy
      to treat extensive eyelid and conjunctival lesions. METHODS: Case report with a
      review of the current literature. RESULTS: Combination of imiquimod 5% cream
      (Aldara, 3M Pharmaceuticals) and cryotherapy for periorbital lentigo maligna with
      topical interferon-alpha2b for conjunctival PAM with atypia led to clinical
      resolution of pigmented lesions for 21 months. CONCLUSIONS: In our experience,
      combination topical therapy provides an effective alternative to surgery with
      superior cosmetic and functional outcomes.

PMID- 25393091
TI  - Impact of donor characteristics on 2-year Descemet stripping automated
      endothelial keratoplasty outcomes in patients with Fuchs endothelial dystrophy.
AB  - PURPOSE: The aim of this study was to determine the relationship between donor
      tissue characteristics and surgical outcomes in patients with Fuchs endothelial
      dystrophy (FED) 2 years after undergoing Descemet stripping automated endothelial
      keratoplasty (DSAEK). METHODS: A retrospective chart review was performed
      identifying 70 eyes with FED that underwent DSAEK. Donor endothelial cell density
      (ECD), donor death to preservation time, donor storage time, donor age, and
      postoperative recipient ECD were evaluated. Statistical analysis was performed
      using univariate linear regression analysis and bidirectional elimination
      multiple stepwise linear regression. RESULTS: Cornea donor age was a predictor of
      postoperative ECD at postoperative years 1 and 2 (P = 0.02, adjusted R2 = 0.07
      and P = 0.002, adjusted R2 = 0.13, respectively). Donor age was also a predictor
      of postoperative ECD at years 1 and 2 after taking into account donor ECD, death
      to preservation time, and donor storage time (P = 0.02, adjusted R2 = 0.62 and P
      = 0.002, adjusted R2 = 0.12, respectively). Donor death to preservation time was
      a predictor of postoperative ECD at only postoperative year 2 (P = 0.03, adjusted
      R2 = 0.05). Donor storage time and donor ECD did not significantly impact
      postoperative ECD. CONCLUSIONS: Although donor age seems to have a statistically
      significant impact on postoperative ECD in patients with FED undergoing DSAEK,
      the relationship is weak. Other donor parameters did not have a consistent or
      significant impact on postoperative ECD.

PMID- 25393092
TI  - Repeatability, reproducibility, and age dependency of dynamic Scheimpflug-based
      pneumotonometer and its correlation with a dynamic bidirectional pneumotonometry
      device.
AB  - PURPOSE: To assess the repeatability, reproducibility, and age dependency of
      dynamic Scheimpflug-based pneumotonometry (Corvis)-generated parameters and their
      correlation with dynamic bidirectional pneumotonometry device [Ocular Response
      Analyzer (ORA)] measurements [corneal hysteresis (CH) and corneal resistance
      factor (CRF)]. METHODS: Eyes of 29 healthy participants between 20 and 30 years
      old were measured using Corvis and ORA. Measurements were performed twice in a
      row and repeated after 1 week. Repeatability and reproducibility were examined by
      calculating intraday and interday coefficients of variation (CVs). Corvis
      measurements were compared with measurements from 19 participants older than 65
      years. RESULTS: The most repeatable and reproducible Corvis-generated parameters,
      with intraday and interday CVs < 10% were as follows: intraocular pressure (IOP),
      pachymetry, time to first and second applanation (A1 time, A2 time), radius and
      amplitude at highest concavity (HC radius and HC deformation amplitude,
      respectively), time to highest concavity (HC time), deflection length and
      amplitude at highest concavity [HC deflection length and HC deflection amplitude
      (millimeter), respectively], and time to highest deflection amplitude [HC
      deflection amplitude (millisecond)]. However, 7 of 19 analyzed parameters showed
      CVs > 10%. HC-related parameters showed significant age dependency. The
      correlation between Corvis and ORA was weak (A2 time and CH, r = 0.36, A1 time
      and CRF, r = 0.41). Corvis-derived IOP was on average 2.2 +/- 2.3 mm Hg higher
      than cornea-compensated IOP, with large differences in patients with high-average
      IOP. CONCLUSIONS: The considerable variation in repeatability and reproducibility
      should be taken into account when using the Corvis. Corvis parameters showed poor
      correlation with CH and CRF obtained by ORA measurements.

PMID- 25393093
TI  - Clostridium perfringens endophthalmitis after penetrating keratoplasty with
      contaminated corneal allografts: a case series.
AB  - PURPOSE: To report the postoperative clinical course of 3 patients who underwent
      corneal transplantation with corneal allografts contaminated with Clostridium
      perfringens and to evaluate the risk factors for anaerobic contamination in 2
      donors. METHODS: Patient records and adverse reaction reports from a single eye
      bank related to cases of posttransplant C. perfringens endophthalmitis were
      reviewed. Records regarding the mated corneas, donor autopsy reports, and other
      pertinent data were also reviewed. RESULTS: Three adverse reactions associated
      with transplantation of corneal allografts contaminated with C. perfringens were
      reported. Two cases were from mated corneas. Both patients developed fulminant
      endophthalmitis after undergoing uncomplicated penetrating keratoplasty and
      required subsequent enucleation. Another isolated case (with no adverse reaction
      in the mate cornea) developed hypopyon postoperatively that resolved with
      intravitreal and topical antibiotics. Possible risk factors for anaerobic tissue
      contamination in the donors included illicit drug use in the first donor and
      exposure to sewage at the time of death in the second donor. CONCLUSIONS:
      Clostridial endophthalmitis is an aggressive rapidly progressive infection with
      potentially poor visual outcomes that can be transmitted from infected corneal
      allografts. Further investigation is needed to clarify the role of anaerobic
      donor rim cultures and the donor risk factors associated with recovering corneal
      allograft tissue contaminated with C. perfringens.

PMID- 25393094
TI  - Treatment of ocular surface squamous neoplasia with topical Aloe vera drops.
AB  - PURPOSE: To report a case of ocular surface squamous neoplasia (OSSN) that
      resolved with topical Aloe vera eye drop treatment. METHODS: A 64-year-old
      Hispanic woman with a lesion typical for OSSN in her left eye was followed up
      with multiple clinical examinations and ocular surface photographs to document
      changes over time with A. vera-based topical treatment. RESULTS: The patient
      refused biopsy of her lesion and traditional treatments and, instead, initiated
      using A. vera eye drops 3 times daily. At follow-up visits, the lesion was noted
      to regress until it finally resolved 3 months after commencing treatment. No
      additional topical medications were used, and she has remained tumor free for 6
      years. CONCLUSIONS: Ongoing research is warranted because A. vera may represent a
      new therapeutic class of medications for OSSN treatment.

PMID- 25393095
TI  - Treatment adherence after penetrating corneal transplant in a New Zealand
      population from 2000 to 2009.
AB  - PURPOSE: The aim of this study was to evaluate the extent of nonadherence after
      penetrating keratoplasty in Auckland, New Zealand, over a 10-year period and to
      identify predictive variables. METHODS: The New Zealand National Eye Bank records
      were analyzed for the decade January 1, 2000, to December 31, 2009, inclusive.
      Variables evaluated included age, gender, ethnicity, proximity to treatment
      center, level of deprivation, indication for surgery, previous ocular surgery.
      The number of scheduled appointments offered and attended by each patient was
      recorded. Outcome measures were appointment compliance and 2-year follow-up
      completion. RESULTS: Over the study period, 1055 corneal transplant procedures
      were identified. After applying exclusion criteria, data from 695 penetrating
      keratoplasty procedures were included in the study. Two-year follow-up
      information was available for 91.4%, of which 87.8% survived and 77 (12.1%)
      failed. Over the study period, 1065 (10.5%) appointments were not attended by
      patients. Appointment compliance was good in 68.5%, moderate in 26.3%, and poor
      in 4.9%. Maori and Pacific Island ethnicities were observed to be associated with
      the lowest level of attendance, whereas European and Indian ethnicities were the
      most likely to complete follow-up. Rates of appointment compliance were greater
      at private treatment centers (P = 0.009) and inversely associated with proximity
      to treatment center (P < 0.0001). CONCLUSIONS: The rate of nonattendance reported
      in this study is considerably higher than that observed in other forms of organ
      transplantation. Both ethnic and socioeconomic factors seem to have a significant
      influence on attendance compliance. Strategies to improve adherence should take
      these factors into account.

PMID- 25393096
TI  - Patients with dry eye without hepatitis C virus infection possess the viral RNA
      in their tears.
AB  - PURPOSE: Dry eye is one of the suggested extrahepatic complications associated
      with hepatitis C virus (HCV) infection. HCV RNA has been detected from the tear
      fluid of patients with chronic HCV. There has been no literature evidence on the
      presence of HCV RNA in the tear fluid of patients with dry eye without HCV
      infection. In this study, tear fluid of patients with dry eye with no HCV
      infection was screened for the presence of HCV RNA. METHODS: Tear fluid was
      collected from patients with dry eye (n = 36) and healthy controls (n = 20). Real
      time polymerase chain reaction was performed to detect HCV RNA in the tear fluid.
      Anti-HCV enzyme-linked immunosorbent assay, alkaline phosphatase, and alanine
      aminotransferase tests were performed in the serum samples collected from 15
      patients with dry eye. RESULTS: Viral RNA was detected in 58.3% of the patients.
      Serum samples collected from 15 patients with dry eye were negative for anti-HCV.
      Alkaline phosphatase levels were elevated in 12 of 15 patients. Alanine
      aminotransferase levels were normal in all 15 patients. The odds ratio for the
      presence of HCV RNA in patients with dry eye was 22.4. CONCLUSIONS: These results
      indicate a direct correlation between dry eye and HCV in non-HCV patients.

PMID- 25393097
TI  - Effect of glaucoma tube shunt parameters on cornea endothelial cells in patients
      with Ahmed valve implants.
AB  - PURPOSE: The aim of this study was to assess the effect of various tube
      parameters on corneal endothelial cell density (ECD) after insertion of Ahmed
      valves. METHODS: Thirty-nine eyes of 33 patients with previous superotemporal
      (ST) Ahmed valve implantation and 20 eyes of 13 participants with previous
      uncomplicated phacoemulsification and intraocular lens implantation but no
      history of glaucoma surgery were evaluated. Various tube parameters were measured
      with anterior segment optical coherence tomography. ST, central, and inferonasal
      (IN) ECD and pachymetry were measured. Endothelial cell loss and corneal
      thickness in the ST cornea was compared with those in the IN cornea. RESULTS: The
      mean age of the operated patients was 58 +/- 22 years, and the mean time since
      glaucoma surgery was 2.5 +/- 2.6 years. Thirty-two of the 39 study eyes were
      pseudophakic. The ECD was significantly lower in the ST endothelium than in the
      IN endothelium in eyes with glaucoma tube surgery (P < 0.001), although this
      relative reduction in ST ECD was not greater than that seen in pseudophakic
      control eyes (P = 0.16). In univariate analysis, tube angle relative to the
      cornea and distance from the tip of the tube to the cornea were significant risk
      factors for decreased ST endothelial cell loss when assessed relative to the IN
      ECD (P = 0.01 and P = 0.02, respectively). In multivariate analysis, only the
      distance of the tube tip to the cornea remained significantly associated with ST
      endothelial cell loss. CONCLUSIONS: Although this was a retrospective study with
      inherent limitations, tubes that are closer to the cornea seem to lead to
      increased loss of adjacent endothelial cells.

PMID- 25393098
TI  - Factors affecting fall down rates of dead aspen (Populus tremuloides) biomass
      following severe drought in west-central Canada.
AB  - Increases in mortality of trembling aspen (Populus tremuloides Michx.) have been
      recorded across large areas of western North America following recent periods of
      exceptionally severe drought. The resultant increase in standing, dead tree
      biomass represents a significant potential source of carbon emissions to the
      atmosphere, but the timing of emissions is partially driven by dead-wood dynamics
      which include the fall down and breakage of dead aspen stems. The rate at which
      dead trees fall to the ground also strongly influences the period over which
      forest dieback episodes can be detected by aerial surveys or satellite remote
      sensing observations. Over a 12-year period (2000-2012), we monitored the annual
      status of 1010 aspen trees that died during and following a severe regional
      drought within 25 study areas across west-central Canada. Observations of stem
      fall down and breakage (snapping) were used to estimate woody biomass transfer
      from standing to downed dead wood as a function of years since tree death. For
      the region as a whole, we estimated that >80% of standing dead aspen biomass had
      fallen after 10 years. Overall, the rate of fall down was minimal during the year
      following stem death, but thereafter fall rates followed a negative exponential
      equation with k = 0.20 per year. However, there was high between-site variation
      in the rate of fall down (k = 0.08-0.37 per year). The analysis showed that fall
      down rates were positively correlated with stand age, site windiness, and the
      incidence of decay fungi (Phellinus tremulae (Bond.) Bond. and Boris.) and wood
      boring insects. These factors are thus likely to influence the rate of carbon
      emissions from dead trees following periods of climate-related forest die-off
      episodes.

PMID- 25393099
TI  - Understanding increases in smoking prevalence: case study from France in
      comparison with England 2000-10.
AB  - AIM: In France, following a long-term decline in smoking prevalence, an increase
      in smoking was observed between 2005 and 2010, an unusual occurrence in countries
      in the 'mature' stage of the smoking epidemic. By contrast, smoking prevalence in
      England, the neighbouring country, continued its long-term decline. METHODS: We
      identified and translated recent reports on smoking and tobacco control in France
      and using these assessed the main data sources on smoking and compared them with
      similar sources in England, in order to explore possible explanations. In France,
      national smoking prevalence data are collected 5-yearly, minimizing opportunities
      for fine-grained analysis; the comparable study in England is implemented
      annually. RESULTS: We identified several probable causes of the recent increased
      prevalence of smoking in France, the primary one being the absence of sufficient
      price rises between 2005 and 2010, due probably to the lack of a robust tobacco
      control strategy, which also appeared to have empowered tobacco industry
      influence. Funding to compensate tobacconists appears to incentivize tobacco
      sales and is significantly higher than tobacco control funding. CONCLUSIONS:
      Mindful of the limitations of a case-study approach, the absence of sufficient
      price rises in the context of a weak tobacco control strategy seems the most
      likely explanation for the recent increase in smoking prevalence in France. A new
      cancer control plan and a national smoking reduction programme have been proposed
      by the French government in 2014 which, depending on implementation, may reverse
      the trend. In both countries, the higher levels of smoking among the more
      disadvantaged groups are of great concern and require greater political
      leadership for effective action.

PMID- 25393100
TI  - Efficient synthesis of aza-triquinacene derivatives via cycloaddition of 2,6
      diazasemibullvalenes with nitroso compounds.
AB  - The reaction between 2,6-diazasemibullvalenes and nitroso compounds was
      investigated. Aza-triquinacene derivatives of interesting structural and
      synthetic chemistry were generated highly selectively in good to excellent
      isolated yields. This reaction, which was rarely found between common aziridine
      derivatives and nitroso compounds, could be attributed to the rigid polycyclic
      ring system and the substitution patterns of 2,6-diazasemibullvalenes. Delta(1) 
      Bipyrroline derivatives were formed in excellent yields when these aza
      triquinacene derivatives were treated with SmI2 . 

PMID- 25393101
TI  - Efficient production of hyperpolarized bicarbonate by chemical reaction on a DNP
      precursor to measure pH.
AB  - PURPOSE: To produce hyperpolarized bicarbonate indirectly via chemical reaction
      from a hyperpolarized precursor and utilize it for the simultaneous regional
      measurement of metabolism and pH. METHODS: Alpha keto carboxylic acids are first
      hyperpolarized by dissolution dynamic nuclear polarization (DNP). These precursor
      molecules are rapidly reacted with hydrogen peroxide (H2O2) to decarboxylate the
      species, resulting in new target molecules. Unreacted H2O2 is removed from the
      system by reaction with sulfite. Interrogation of the ratio of dissolved carbon
      dioxide (CO2) to bicarbonate can be used to determine pH. RESULTS: Conversion of
      hyperpolarized alpha keto acids to bicarbonate and CO2 results in a minimal loss
      of the spin order. The reaction can be conducted to completion within seconds and
      preserves the nuclear spin polarization. CONCLUSION: Through a rapid chemical
      reaction, we can conserve the nuclear spin order of a DNP precursor to generate
      multiple hyperpolarized bioprobes otherwise unamenable to polarization. This
      indirect technique for the production of hyperpolarized agents can be applied to
      different precursor compounds to generate additional novel probes.

PMID- 25393102
TI  - Sequential control over thiol click chemistry by a reversibly photoactivated
      thiol mechanism of spirothiopyran.
AB  - A novel photocontrolled thiol click chemistry based on spirothiopyran and
      maleimide is reported. Upon irradiation with lambda=365 nm light, the
      spirothiopyran can isomerize to the open merocyanine form, a thiophenolate group,
      which can rapidly react with maleimide. The unreacted MC will readily isomerize
      back to the starting spirothiopyran, which can be repeatedly photoactivated as
      needed. Thus, this reversible photoactivated thiol confers spatiotemporal
      sequential control on the thiol-maleimide reaction using only one type of
      photochemical reaction. Polymer post-functionalization and hydrogel building with
      subsequent multipatterning using different maleimide molecules in a temporal
      sequential manner indicate that this photocontrolled Michael addition reaction
      can modulate the specific chemical events in a sequence. 

PMID- 25393103
TI  - Sialendoscopy for the management of juvenile recurrent parotitis: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To determine the effectiveness and safety of sialendoscopy for the
      treatment of juvenile recurrent parotitis (JRP). The study was conducted and
      reported in accordance with the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines. DATA SOURCES: A comprehensive search strategy in
      MEDLINE, EMBASE, the Cochrane library, and Google Scholar was completed and
      limited to studies published in English. Relevant reference lists were reviewed.
      STUDY SELECTION: Two independent reviewers selected prospective or retrospective
      studies of pediatric patients treated with interventional sialendoscopy for the
      management of JRP. Outcome measures included rates of successful treatment (no
      further episodes of parotid swelling or need for further sialendoscopy) and
      complications, DATA EXTRACTION: Two reviewers appraised the level of evidence
      using the Oxford Clinical Evidence-based Medicine (OCEBM) guidelines, extracted
      data, and resolved discrepancies by consensus. Weighted pooled proportion, 95%
      confidence interval (CI), and test results for heterogeneity and publication bias
      are reported. RESULTS: Seven studies were included. Levels of evidence varied
      from OCEBM level 3 to 4. The weighted pooled proportion of success rates for no
      further episodes by patient (n = 120) was 73% (95% CI: 64%-82%) and by gland (n =
      165) 81% (95% CI: 75%-87%). The weighted pooled proportion of success rates for
      no further sialendoscopy by patient was 87% (95% CI: 81%-93%). Heterogeneity was
      low, and publication bias was not detected. There were no major complications
      reported. Surgical techniques and endoscopic findings are summarized.
      CONCLUSIONS: The results from this analysis suggest that sialendoscopy is
      effective and safe for the treatment of JRP and may be offered to appropriate
      patients. LEVEL OF EVIDENCE: NA

PMID- 25393104
TI  - Salvage combined chemotherapy with paclitaxel, ifosfamide and nedaplatin for
      patients with advanced germ cell tumors.
AB  - OBJECTIVES: To investigate the efficacy of combined regimen with paclitaxel,
      ifosfamide and nedaplatin as salvage chemotherapy in patients with cisplatin
      refractory or multiple relapsed germ cell tumors. METHODS: A total of 65 patients
      refractory to cisplatin-based chemotherapy or with relapse after induction or
      salvage chemotherapy received paclitaxel 210 mg/m(2) on day 1, ifosfamide 1.2
      g/m(2) on days 2-6 and nedaplatin 100 mg/m(2) on day 2 of a 3-week cycle. The
      primary and secondary end-points were the response rate and overall survival,
      respectively. RESULTS: Paclitaxel, ifosfamide and nedaplatin therapy was carried
      out as second-line therapy in 17 patients, third-line in 31 and fourth-line or
      later in 17. Patients were pretreated with a median of six cycles of platinum
      based chemotherapy (range 3-15 cycles). The overall response rate was 62.9%,
      including one patient with complete response and 38 with partial response. Serum
      tumor marker levels normalized in 35 (56.5%) patients. Overall survival at a
      median follow up of 34 months was 59.3%, and median time to progression was 12
      months. Multivariate analysis showed that serum tumor marker normalization was
      the only independent predictor of better progression-free survival and overall
      survival. Grade 3/4 of neutropenia, anemia and thrombocytopenia was observed in
      96.9%, in 81.5%, and in 90.8% of patients, respectively. CONCLUSION: Paclitaxel,
      ifosfamide and nedaplatin chemotherapy appears to be effective when used as first
      or second salvage treatment in advanced relapsed germ cell tumors. Even after
      fourth-line therapy, patients with serum tumor marker normalization might have a
      chance for a cure.

PMID- 25393105
TI  - Clonal architectures and driver mutations in metastatic melanomas.
AB  - To reveal the clonal architecture of melanoma and associated driver mutations,
      whole genome sequencing (WGS) and targeted extension sequencing were used to
      characterize 124 melanoma cases. Significantly mutated gene analysis using 13 WGS
      cases and 15 additional paired extension cases identified known melanoma genes
      such as BRAF, NRAS, and CDKN2A, as well as a novel gene EPHA3, previously
      implicated in other cancer types. Extension studies using tumors from another 96
      patients discovered a large number of truncation mutations in tumor suppressors
      (TP53 and RB1), protein phosphatases (e.g., PTEN, PTPRB, PTPRD, and PTPRT), as
      well as chromatin remodeling genes (e.g., ASXL3, MLL2, and ARID2). Deep
      sequencing of mutations revealed subclones in the majority of metastatic tumors
      from 13 WGS cases. Validated mutations from 12 out of 13 WGS patients exhibited a
      predominant UV signature characterized by a high frequency of C->T transitions
      occurring at the 3' base of dipyrimidine sequences while one patient (MEL9) with
      a hypermutator phenotype lacked this signature. Strikingly, a subclonal mutation
      signature analysis revealed that the founding clone in MEL9 exhibited UV
      signature but the secondary clone did not, suggesting different mutational
      mechanisms for two clonal populations from the same tumor. Further analysis of
      four metastases from different geographic locations in 2 melanoma cases revealed
      phylogenetic relationships and highlighted the genetic alterations responsible
      for differential drug resistance among metastatic tumors. Our study suggests that
      clonal evaluation is crucial for understanding tumor etiology and drug resistance
      in melanoma. 

PMID- 25393111
TI  - Seasonal training-load quantification in elite English premier league soccer
      players.
AB  - PURPOSE: To quantify the seasonal training load completed by professional soccer
      players of the English Premier League. METHODS: Thirty players were sampled
      (using GPS, heart rate, and rating of perceived exertion [RPE]) during the daily
      training sessions of the 2011-12 preseason and in-season period. Preseason data
      were analyzed across 6*1-wk microcycles. In-season data were analyzed across 6*6
      wk mesocycle blocks and 3*1-wk microcycles at start, midpoint, and end-time
      points. Data were also analyzed with respect to number of days before a match.
      RESULTS: Typical daily training load (ie, total distance, high-speed distance,
      percent maximal heart rate [%HRmax], RPE load) did not differ during each week of
      the preseason phase. However, daily total distance covered was 1304 (95% CI 434
      2174) m greater in the 1st mesocycle than in the 6th. %HRmax values were also
      greater (3.3%, 1.3-5.4%) in the 3rd mesocycle than in the first. Furthermore,
      training load was lower on the day before match (MD-1) than 2 (MD-2) to 5 (MD-5)
      d before a match, although no difference was apparent between these latter time
      points. CONCLUSIONS: The authors provide the 1st report of seasonal training load
      in elite soccer players and observed that periodization of training load was
      typically confined to MD-1 (regardless of mesocycle), whereas no differences were
      apparent during MD-2 to MD-5. Future studies should evaluate whether this loading
      and periodization are facilitative of optimal training adaptations and match-day
      performance.

PMID- 25393108
TI  - Highly polygenic variation in environmental perception determines dauer larvae
      formation in growing populations of Caenorhabditis elegans.
AB  - BACKGROUND: Determining how complex traits are genetically controlled is a
      requirement if we are to predict how they evolve and how they might respond to
      selection. This requires understanding how distinct, and often more simple, life
      history traits interact and change in response to environmental conditions. In
      order to begin addressing such issues, we have been analyzing the formation of
      the developmentally arrested dauer larvae of Caenorhabditis elegans under
      different conditions. RESULTS: We find that 18 of 22 previously identified
      quantitative trait loci (QTLs) affecting dauer larvae formation in growing
      populations, assayed by determining the number of dauer larvae present at food
      patch exhaustion, can be recovered under various environmental conditions. We
      also show that food patch size affects both the ability to detect QTLs and
      estimates of effect size, and demonstrate that an allele of nath-10 affects dauer
      larvae formation in growing populations. To investigate the component traits that
      affect dauer larvae formation in growing populations we map, using the same
      introgression lines, QTLs that affect dauer larvae formation in response to
      defined amounts of pheromone. This identifies 36 QTLs, again demonstrating the
      highly polygenic nature of the genetic variation underlying dauer larvae
      formation. CONCLUSIONS: These data indicate that QTLs affecting the number of
      dauer larvae at food exhaustion in growing populations of C. elegans are highly
      reproducible, and that nearly all can be explained by variation affecting dauer
      larvae formation in response to defined amounts of pheromone. This suggests that
      most variation in dauer larvae formation in growing populations is a consequence
      of variation in the perception of the food and pheromone environment (i.e.
      chemosensory variation) and in the integration of these cues.

PMID- 25393109
TI  - Heterogeneity of Particle Deposition by Pixel Analysis of 2D Gamma Scintigraphy
      Images.
AB  - BACKGROUND: Heterogeneity of inhaled particle deposition in airways disease may
      be a sensitive indicator of physiologic changes in the lungs. Using planar gamma
      scintigraphy, we developed new methods to locate and quantify regions of high
      (hot) and low (cold) particle deposition in the lungs. METHODS: Initial
      deposition and 24 hour retention images were obtained from healthy (n=31) adult
      subjects and patients with mild cystic fibrosis lung disease (CF) (n=14)
      following inhalation of radiolabeled particles (Tc99m-sulfur colloid, 5.4 MUm
      MMAD) under controlled breathing conditions. The initial deposition image of the
      right lung was normalized to (i.e., same median pixel value), and then divided
      by, a transmission (Tc99m) image in the same individual to obtain a pixel-by
      pixel ratio image. Hot spots were defined where pixel values in the deposition
      image were greater than 2X those of the transmission, and cold spots as pixels
      where the deposition image was less than 0.5X of the transmission. The number
      ratio (NR) of the hot and cold pixels to total lung pixels, and the sum ratio
      (SR) of total counts in hot pixels to total lung counts were compared between
      healthy and CF subjects. Other traditional measures of regional particle
      deposition, nC/P and skew of the pixel count histogram distribution, were also
      compared. RESULTS: The NR of cold spots was greater in mild CF, 0.221+/-0.047(CF)
      vs. 0.186+/-0.038 (healthy) (p<0.005) and was significantly correlated with FEV1
      %pred in the patients (R=-0.70). nC/P (central to peripheral count ratio), skew
      of the count histogram, and hot NR or SR were not different between the healthy
      and mild CF patients. CONCLUSIONS: These methods may provide more sensitive
      measures of airway function and localization of deposition that might be useful
      for assessing treatment efficacy in these patients.

PMID- 25393107
TI  - Protein thermal stability enhancement by designing salt bridges: a combined
      computational and experimental study.
AB  - Protein thermal stability is an important factor considered in medical and
      industrial applications. Many structural characteristics related to protein
      thermal stability have been elucidated, and increasing salt bridges is considered
      as one of the most efficient strategies to increase protein thermal stability.
      However, the accurate simulation of salt bridges remains difficult. In this
      study, a novel method for salt-bridge design was proposed based on the
      statistical analysis of 10,556 surface salt bridges on 6,493 X-ray protein
      structures. These salt bridges were first categorized based on pairing residues,
      secondary structure locations, and Calpha-Calpha distances. Pairing preferences
      generalized from statistical analysis were used to construct a salt-bridge pair
      index and utilized in a weighted electrostatic attraction model to find the
      effective pairings for designing salt bridges. The model was also coupled with B
      factor, weighted contact number, relative solvent accessibility, and conservation
      prescreening to determine the residues appropriate for the thermal adaptive
      design of salt bridges. According to our method, eight putative salt-bridges were
      designed on a mesophilic beta-glucosidase and 24 variants were constructed to
      verify the predictions. Six putative salt-bridges leaded to the increase of the
      enzyme thermal stability. A significant increase in melting temperature of 8.8,
      4.8, 3.7, 1.3, 1.2, and 0.7 degrees C of the putative salt-bridges N437K-D49,
      E96R-D28, E96K-D28, S440K-E70, T231K-D388, and Q277E-D282 was detected,
      respectively. Reversing the polarity of T231K-D388 to T231D-D388K resulted in a
      further increase in melting temperatures by 3.6 degrees C, which may be caused by
      the transformation of an intra-subunit electrostatic interaction into an inter
      subunit one depending on the local environment. The combination of the
      thermostable variants (N437K, E96R, T231D and D388K) generated a melting
      temperature increase of 15.7 degrees C. Thus, this study demonstrated a novel
      method for the thermal adaptive design of salt bridges through inference of
      suitable positions and substitutions. 

PMID- 25393110
TI  - Retromer regulates HIV-1 envelope glycoprotein trafficking and incorporation into
      virions.
AB  - The envelope glycoprotein (Env) of the Human Immunodeficiency Virus Type-1 (HIV
      1) is a critical determinant of viral infectivity, tropism and is the main target
      for humoral immunity; however, little is known about the cellular machinery that
      directs Env trafficking and its incorporation into nascent virions. Here we
      identify the mammalian retromer complex as a novel and important cellular factor
      regulating Env trafficking. Retromer mediates endosomal sorting and is most
      closely associated with endosome-to-Golgi transport. Consistent with this
      function, inactivating retromer using RNAi targeting the cargo selective trimer
      complex inhibited retrograde trafficking of endocytosed Env to the Golgi.
      Notably, in HIV-1 infected cells, inactivating retromer modulated plasma membrane
      expression of Env, along with Env incorporation into virions and particle
      infectivity. Mutagenesis studies coupled with coimmunoprecipitations revealed
      that retromer-mediated trafficking requires the Env cytoplasmic tail that we show
      binds directly to retromer components Vps35 and Vps26. Taken together these
      results provide novel insight into regulation of HIV-1 Env trafficking and
      infectious HIV-1 morphogenesis and show for the first time a role for retromer in
      the late-steps of viral replication and assembly of a virus. 

PMID- 25393113
TI  - A system for heart sounds classification.
AB  - The future of quick and efficient disease diagnosis lays in the development of
      reliable non-invasive methods. As for the cardiac diseases - one of the major
      causes of death around the globe - a concept of an electronic stethoscope
      equipped with an automatic heart tone identification system appears to be the
      best solution. Thanks to the advancement in technology, the quality of
      phonocardiography signals is no longer an issue. However, appropriate algorithms
      for auto-diagnosis systems of heart diseases that could be capable of
      distinguishing most of known pathological states have not been yet developed. The
      main issue is non-stationary character of phonocardiography signals as well as a
      wide range of distinguishable pathological heart sounds. In this paper a new
      heart sound classification technique, which might find use in medical diagnostic
      systems, is presented. It is shown that by combining Linear Predictive Coding
      coefficients, used for future extraction, with a classifier built upon combining
      Support Vector Machine and Modified Cuckoo Search algorithm, an improvement in
      performance of the diagnostic system, in terms of accuracy, complexity and range
      of distinguishable heart sounds, can be made. The developed system achieved
      accuracy above 93% for all considered cases including simultaneous identification
      of twelve different heart sound classes. The respective system is compared with
      four different major classification methods, proving its reliability. 

PMID- 25393106
TI  - Molecular dynamics studies of the inhibitor C34 binding to the wild-type and
      mutant HIV-1 gp41: inhibitory and drug resistant mechanism.
AB  - Mutations on NHR (N-terminal heptad repeat) associated with resistance to fusion
      inhibitor were observed. In addition, mutations on CHR (C-terminal heptad repeat)
      accompanied NHR mutations of gp41 are noted in many cases, like N43D/S138A double
      mutation. In this work, we explored the drug resistant mechanism of N43D mutation
      and the role of S138A second mutation in drug resistance. The binding modes of
      the wild type gp41 and the two mutants, N43D and N43D/S138A, with the HIV-1
      fusion inhibitor C34, a 34-residue peptide mimicking CHR of gp41, were carried
      out by using molecular dynamics simulations. Based on the MD simulations, N43D
      mutation affects not only the stability of C34 binding, but also the binding
      energy of the inhibitor C34. Because N43D mutation may also affect the stable
      conformation of 6-HB, we introduced S138A second mutation into CHR of gp41 and
      determined the impact of this mutation. Through the comparative analysis of MD
      results of the N43D mutant and the N43D/S138A mutant, we found that CHR with
      S138A mutation shown more favorable affinity to NHR. Compelling differences in
      structures have been observed for these two mutants, particularly in the binding
      modes and in the hydrophobic interactions of the CHR (C34) located near the
      hydrophobic groove of the NHR. Because the conformational stability of 6-HB is
      important to HIV-1 infection, we suggested a hypothetical mechanism for the drug
      resistance: N43D single mutation not only impact the binding of inhibitor, but
      also affect the affinity between NHR and CHR of gp41, thus may reduce the rate of
      membrane fusion; compensatory mutation S138A would induce greater hydrophobic
      interactions between NHR and CHR, and render the CHR more compatible to NHR than
      inhibitors. 

PMID- 25393112
TI  - RNA-seq analysis of Quercus pubescens Leaves: de novo transcriptome assembly,
      annotation and functional markers development.
AB  - Quercus pubescens Willd., a species distributed from Spain to southwest Asia,
      ranks high for drought tolerance among European oaks. Q. pubescens performs a
      role of outstanding significance in most Mediterranean forest ecosystems, but few
      mechanistic studies have been conducted to explore its response to environmental
      constrains, due to the lack of genomic resources. In our study, we performed a
      deep transcriptomic sequencing in Q. pubescens leaves, including de novo
      assembly, functional annotation and the identification of new molecular markers.
      Our results are a pre-requisite for undertaking molecular functional studies, and
      may give support in population and association genetic studies. 254,265,700 clean
      reads were generated by the Illumina HiSeq 2000 platform, with an average length
      of 98 bp. De novo assembly, using CLC Genomics, produced 96,006 contigs, having a
      mean length of 618 bp. Sequence similarity analyses against seven public
      databases (Uniprot, NR, RefSeq and KOGs at NCBI, Pfam, InterPro and KEGG)
      resulted in 83,065 transcripts annotated with gene descriptions, conserved
      protein domains, or gene ontology terms. These annotations and local BLAST
      allowed identify genes specifically associated with mechanisms of drought
      avoidance. Finally, 14,202 microsatellite markers and 18,425 single nucleotide
      polymorphisms (SNPs) were, in silico, discovered in assembled and annotated
      sequences. We completed a successful global analysis of the Q. pubescens leaf
      transcriptome using RNA-seq. The assembled and annotated sequences together with
      newly discovered molecular markers provide genomic information for functional
      genomic studies in Q. pubescens, with special emphasis to response mechanisms to
      severe constrain of the Mediterranean climate. Our tools enable comparative
      genomics studies on other Quercus species taking advantage of large intra
      specific ecophysiological differences. 

PMID- 25393114
TI  - Naphthalene-, anthracene-, and pyrene-substituted fullerene derivatives as
      electron acceptors in polymer-based solar cells.
AB  - A series of aryl-substituted fullerene derivatives were prepared in which the
      aromatic moiety of [6,6]-phenyl C61-butyric acid methyl ester (PC61BM) was
      modified by replacing the monocyclic phenyl ring with bicyclic naphthalene
      (NC61BM), tricyclic anthracene (AC61BM), and tetracyclic pyrene (PyC61BM). The
      PC61BM derivatives were synthesized from C60 using tosylhydrazone and were tested
      as electron acceptors in poly(3-hexylthiophene) (P3HT)-based organic photovoltaic
      cells (OPVs). The lowest unoccupied molecular orbital (LUMO) energy level of
      NC61BM (-3.68 eV) was found to be slightly higher than those of PC61BM (-3.70
      eV), AC61BM (-3.75 eV), and PyC61BM (-3.72 eV). The electron mobility values
      obtained for the P3HT:PC61BM, P3HT:NC61BM, P3HT:AC61BM, and P3HT:PyC61BM blend
      films were 2.39 * 10(-4), 2.27 * 10(-4), 1.75 * 10(-4), and 2.13 * 10(-4) cm(2)
      V(-1) s(-1), respectively. P3HT-based bulk-heterojunction (BHJ) solar cells were
      fabricated using NC61BM, AC61BM, and PyC61BM as electron acceptors, and their
      performances were compared with that of the device fabricated using PC61BM. The
      highest power conversion efficiencies (PCEs) observed for devices fabricated with
      PC61BM, NC61BM, AC61BM, and PyC61BM were 3.80, 4.09, 1.14, and 1.95%,
      respectively, suggesting NC61BM as a promising electron acceptor for OPVs.

PMID- 25393115
TI  - Possible contribution of taurine to distorted glucagon secretion in intra-islet
      insulin deficiency: a metabolome analysis using a novel alpha-cell model of
      insulin-deficient diabetes.
AB  - Glycemic instability is a serious problem in patients with insulin-deficient
      diabetes, and it may be due in part to abnormal endogenous glucagon secretion.
      However, the intracellular metabolic mechanism(s) involved in the aberrant
      glucagon response under the condition of insulin deficiency has not yet been
      elucidated. To investigate the metabolic traits that underlie the distortion of
      glucagon secretion under insulin deficient conditions, we generated an alphaTC1-6
      cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro
      alpha-cell model for insulin-deficient diabetes, which exhibits an abnormal
      glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD
      alphaTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels
      differed markedly compared to those in control alphaTC1-6 cells, but also which
      could affect the glucagon release in IRKD cells. Of these candidates, taurine was
      remarkably increased in the IRKD cells and was identified as a stimulator of
      glucagon in alphaTC1-6 cells. Taurine also paradoxically exaggerated the glucagon
      secretion at a high glucose concentration in IRKD cells and islets with IRKD.
      These results indicate that the metabolic alterations induced by IRKD in alpha
      cells, especially the increase of taurine, may lead to the distorted glucagon
      response in IRKD cells, suggesting the importance of taurine in the paradoxical
      glucagon response and the resultant glucose instability in insulin-deficient
      diabetes. 

PMID- 25393116
TI  - A high-yield co-expression system for the purification of an intact Drs2p-Cdc50p
      lipid flippase complex, critically dependent on and stabilized by
      phosphatidylinositol-4-phosphate.
AB  - P-type ATPases from the P4 subfamily (P4-ATPases) are energy-dependent
      transporters, which are thought to establish lipid asymmetry in eukaryotic cell
      membranes. Together with their Cdc50 accessory subunits, P4-ATPases couple ATP
      hydrolysis to lipid transport from the exoplasmic to the cytoplasmic leaflet of
      plasma membranes, late Golgi membranes, and endosomes. To gain insights into the
      structure and function of these important membrane pumps, robust protocols for
      expression and purification are required. In this report, we present a procedure
      for high-yield co-expression of a yeast flippase, the Drs2p-Cdc50p complex. After
      recovery of yeast membranes expressing both proteins, efficient purification was
      achieved in a single step by affinity chromatography on streptavidin beads,
      yielding ~ 1-2 mg purified Drs2p-Cdc50p complex per liter of culture.
      Importantly, the procedure enabled us to recover a fraction that mainly contained
      a 1:1 complex, which was assessed by size-exclusion chromatography and mass
      spectrometry. The functional properties of the purified complex were examined,
      including the dependence of its catalytic cycle on specific lipids. The
      dephosphorylation rate was stimulated in the simultaneous presence of the
      transported substrate, phosphatidylserine (PS), and the regulatory lipid
      phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide that plays critical
      roles in membrane trafficking events from the trans-Golgi network (TGN).
      Likewise, overall ATP hydrolysis by the complex was critically dependent on the
      simultaneous presence of PI4P and PS. We also identified a prominent role for
      PI4P in stabilization of the Drs2p-Cdc50p complex towards temperature- or C12E8
      induced irreversible inactivation. These results indicate that the Drs2p-Cdc50p
      complex remains functional after affinity purification and that PI4P as a
      cofactor tightly controls its stability and catalytic activity. This work offers
      appealing perspectives for detailed structural and functional characterization of
      the Drs2p-Cdc50p lipid transport mechanism.

PMID- 25393117
TI  - The Glasgow Prognostic Score predicts poor survival in cisplatin-based treated
      patients with metastatic nasopharyngeal carcinoma.
AB  - BACKGROUND: Several inflammation-based prognostic scoring systems, including
      Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR) and platelet
      to lymphocyte ratio (PLR) have been reported to predict survival in many
      malignancies, whereas their role in metastatic nasopharyngeal carcinoma (NPC)
      remains unclear. The aim of this study is to evaluate the clinical value of these
      prognostic scoring systems in a cohort of cisplatin-based treated patients with
      metastatic NPC. METHODS: Two hundred and eleven patients with histologically
      proven metastatic NPC treated with first-line cisplatin-based chemotherapy were
      retrospectively evaluated. Demographics, disease-related characteristics and
      relevant laboratory data before treatment were recorded. GPS, NLR and PLR were
      calculated as described previously. Response to first-line therapy and survival
      data were also collected. Survival was analyzed in Cox regressions and stability
      of the models was examined by bootstrap resampling. The area under the receiver
      operating characteristics curve (AUC) was calculated to compare the
      discriminatory ability of each scoring system. RESULTS: Among the above three
      inflammation-based prognostic scoring systems, GPS (P<0.001) and NLR (P = 0.019)
      were independently associated with overall survival, which showed to be stable in
      a bootstrap resampling study. The GPS consistently showed a higher AUC value at 6
      month (0.805), 12-month (0.705), and 24-month (0.705) in comparison with NLR and
      PLR. Further analysis of the association of GPS with progression-free survival
      showed GPS was also associated independently with progression-free survival
      (P<0.001). CONCLUSIONS: Our study demonstrated that the GPS may be of prognostic
      value in metastatic NPC patients treated with cisplatin-based palliative
      chemotherapy and facilitate individualized treatment. However a prospective study
      to validate this prognostic model is still needed.

PMID- 25393118
TI  - Strengthening neglected tropical disease research through enhancing research-site
      capacity: an evaluation of a novel web application to facilitate research
      collaborations.

PMID- 25393119
TI  - Phylogenetic analysis of algal symbionts associated with four North American
      amphibian egg masses.
AB  - Egg masses of the yellow-spotted salamander Ambystoma maculatum form an
      association with the green alga "Oophila amblystomatis" (Lambert ex Wille),
      which, in addition to growing within individual egg capsules, has recently been
      reported to invade embryonic tissues and cells. The binomial O. amblystomatis
      refers to the algae that occur in A. maculatum egg capsules, but it is unknown
      whether this population of symbionts constitutes one or several different algal
      taxa. Moreover, it is unknown whether egg masses across the geographic range of
      A. maculatum, or other amphibians, associate with one or multiple algal taxa. To
      address these questions, we conducted a phylogeographic study of algae sampled
      from egg capsules of A. maculatum, its allopatric congener A. gracile, and two
      frogs: Lithobates sylvatica and L. aurora. All of these North American amphibians
      form associations with algae in their egg capsules. We sampled algae from egg
      capsules of these four amphibians from localities across North America,
      established representative algal cultures, and amplified and sequenced a region
      of 18S rDNA for phylogenetic analysis. Our combined analysis shows that symbiotic
      algae found in egg masses of four North American amphibians are closely related
      to each other, and form a well-supported clade that also contains three strains
      of free-living chlamydomonads. We designate this group as the 'Oophila' clade,
      within which the symbiotic algae are further divided into four distinct
      subclades. Phylogenies of the host amphibians and their algal symbionts are only
      partially congruent, suggesting that host-switching and co-speciation both play
      roles in their associations. We also established conditions for isolating and
      rearing algal symbionts from amphibian egg capsules, which should facilitate
      further study of these egg mass specialist algae. 

PMID- 25393121
TI  - Deep vision: an in-trawl stereo camera makes a step forward in monitoring the
      pelagic community.
AB  - Ecosystem surveys are carried out annually in the Barents Sea by Russia and
      Norway to monitor the spatial distribution of ecosystem components and to study
      population dynamics. One component of the survey is mapping the upper pelagic
      zone using a trawl towed at several depths. However, the current technique with a
      single codend does not provide fine-scale spatial data needed to directly study
      species overlaps. An in-trawl camera system, Deep Vision, was mounted in front of
      the codend in order to acquire continuous images of all organisms passing. It was
      possible to identify and quantify of most young-of-the-year fish (e.g. Gadus
      morhua, Boreogadus saida and Reinhardtius hippoglossoides) and zooplankton,
      including Ctenophora, which are usually damaged in the codend. The system showed
      potential for measuring the length of small organisms and also recorded the
      vertical and horizontal positions where individuals were imaged. Young-of-the
      year fish were difficult to identify when passing the camera at maximum range and
      to quantify during high densities. In addition, a large number of fish with
      damaged opercula were observed passing the Deep Vision camera during heaving;
      suggesting individuals had become entangled in meshes farther forward in the
      trawl. This indicates that unknown numbers of fish are probably lost in forward
      sections of the trawl and that the heaving procedure may influence the number of
      fish entering the codend, with implications for abundance indices and
      understanding population dynamics. This study suggests modifications to the Deep
      Vision and the trawl to increase our understanding of the population dynamics. 

PMID- 25393120
TI  - The talin head domain reinforces integrin-mediated adhesion by promoting adhesion
      complex stability and clustering.
AB  - Talin serves an essential function during integrin-mediated adhesion in linking
      integrins to actin via the intracellular adhesion complex. In addition, the N
      terminal head domain of talin regulates the affinity of integrins for their ECM
      ligands, a process known as inside-out activation. We previously showed that in
      Drosophila, mutating the integrin binding site in the talin head domain resulted
      in weakened adhesion to the ECM. Intriguingly, subsequent studies showed that
      canonical inside-out activation of integrin might not take place in flies.
      Consistent with this, a mutation in talin that specifically blocks its ability to
      activate mammalian integrins does not significantly impinge on talin function
      during fly development. Here, we describe results suggesting that the talin head
      domain reinforces and stabilizes the integrin adhesion complex by promoting
      integrin clustering distinct from its ability to support inside-out activation.
      Specifically, we show that an allele of talin containing a mutation that disrupts
      intramolecular interactions within the talin head attenuates the assembly and
      reinforcement of the integrin adhesion complex. Importantly, we provide evidence
      that this mutation blocks integrin clustering in vivo. We propose that the talin
      head domain is essential for regulating integrin avidity in Drosophila and that
      this is crucial for integrin-mediated adhesion during animal development. 

PMID- 25393123
TI  - Conserved and novel heat stress-responsive microRNAs were identified by deep
      sequencing in Saccharina japonica (Laminariales, Phaeophyta).
AB  - As a temperate-cold species, Saccharina japonica often suffers heat stress when
      it is transplanted to temperate and subtropical zones. Study the heat stress
      response and resistance mechanism of Saccharina is of great significance for
      understanding the acclimation to heat stress under domestication as well as for
      breeding new cultivars with heat stress resistance. In this study, we identified
      a set of heat stress-responsive miRNAs and analysed their regulation during the
      heat stress response. CO (control) and heat stress (HS) sRNA libraries were
      constructed and sequenced. Forty-nine known miRNAs and 75 novel miRNAs were
      identified, of which seven known and 25 novel miRNAs were expressed
      differentially under heat stress. Quantitative PCR of six selected miRNAs
      confirmed that these loci were responsive to heat stress. Thirty-nine and 712
      genes were predicted to be targeted by the seven known miRNAs and 25 novel
      miRNAs, respectively. Gene function and pathway analyses showed that these genes
      probably play important roles in S. japonica heat stress tolerance. The miRNAs
      identified represent the first set of heat-responsive miRNAs identified from S.
      japonica, and their identification can help elucidate the heat stress response
      and resistance mechanisms in S. japonica.

PMID- 25393125
TI  - Cue-induced craving in pathological buying: empirical evidence and clinical
      implications.
AB  - OBJECTIVE: Pathological buying is associated with marked distress and impaired
      functioning in important life domains. It is currently under debate whether
      pathological buying can be considered a behavioral addiction. In analogy to
      results reported in addicted individuals, craving reactions elicited by addiction
      related cues might be an underlying mechanism for the etiology and pathogenesis
      of pathological buying. METHODS: In the present study, 30 pathological buyers and
      30 matched control participants were examined with a cue-reactivity paradigm
      consisting of shopping and control cues. Skin conductance responses, as well as
      subjective ratings for arousal, valence, and urge to buy, were assessed.
      Subjective craving reactions were measured before and after the cue-reactivity
      paradigm. RESULTS: On a physiological level, skin conductance responses toward
      shopping cues were higher in pathological buyers (mean [M; standard deviation
      {SD}] = 0.26 [0.13]) compared with control participants (M [SD] = 0.19 [0.09];
      t(58) = 2.29, p = .025, d = 0.60). On a behavioral level, the individuals with
      pathological buying rated the shopping cues as more arousing and more positive,
      and reported a greater urge to buy compared with control participants and with
      control cues. An increase in subjective craving after completing the cue
      reactivity paradigm was observed only in the pathological buyers (Mpre [SD] =
      1.95 [1.47], Mpost [SD] = 2.87 [1.79]; t(29) = 5.07, p < .001, d = 0.97).
      CONCLUSIONS: Cue-reactivity and craving might be potential correlates for the
      development and maintenance of pathological buying. The results demonstrate
      similarities between pathological buying and substance or behavioral addictions
      and provide implications for clinical treatment.

PMID- 25393122
TI  - Poly(I:C) induces antiviral immune responses in Japanese flounder (Paralichthys
      olivaceus) that require TLR3 and MDA5 and is negatively regulated by Myd88.
AB  - Polyinosinic:polycytidylic acid (poly(I:C)) is a ligand of toll-like receptor
      (TLR) 3 that has been used as an immunostimulant in humans and mice against viral
      diseases based on its ability to enhance innate and adapt immunity. Antiviral
      effect of poly(I:C) has also been observed in teleost, however, the underling
      mechanism is not clear. In this study, we investigated the potential and
      signaling mechanism of poly(I:C) as an antiviral agent in a model of Japanese
      flounder (Paralichthys olivaceus) infected with megalocytivirus. We found that
      poly(I:C) exhibited strong antiviral activity and enhanced activation of head
      kidney macrophages and peripheral blood leukocytes. In vivo studies showed that
      (i) TLR3 as well as MDA5 knockdown reduced poly(I:C)-mediated immune response and
      antiviral activity to significant extents; (ii) when Myd88 was overexpressed in
      flounder, poly(I:C)-mediated antiviral activity was significantly decreased;
      (iii) when Myd88 was inactivated, the antiviral effect of poly(I:C) was
      significantly increased. Cellular study showed that (i) the NF-kappaB activity
      induced by poly(I:C) was upregulated in Myd88-overexpressing cells and unaffected
      in Myd88-inactivated cells; (ii) Myd88 overexpression inhibited and upregulated
      the expression of poly(I:C)-induced antiviral genes and inflammatory genes
      respectively; (iii) Myd88 inactivation enhanced the expression of the antiviral
      genes induced by poly(I:C). Taken together, these results indicate that poly(I:C)
      is an immunostimulant with antiviral potential, and that the immune response of
      poly(I:C) requires TLR3 and MDA5 and is negatively regulated by Myd88 in a manner
      not involving NK-kappaB. These results provide insights to the working mechanism
      of poly(I:C), TLR3, and Myd88 in fish. 

PMID- 25393126
TI  - Physiologic characterization of the chronic bronchitis phenotype in GOLD grade IB
      COPD.
AB  - BACKGROUND: Smokers with persistent cough and sputum production (chronic
      bronchitis [CB]) represent a distinct clinical phenotype, consistently linked to
      negative clinical outcomes. However, the mechanistic link between physiologic
      impairment, dyspnea, and exercise intolerance in CB has not been studied,
      particularly in those with mild airway obstruction. We, therefore, compared
      physiologic abnormalities during rest and exercise in CB to those in patients
      without symptoms of mucus hypersecretion (non-CB) but with similar mild airway
      obstruction. METHODS: Twenty patients with CB (>= 3 months cough/sputum in 2
      successive years), 20 patients without CB but with GOLD (Global Initiative for
      Chronic Obstructive Lung Disease) grade IB COPD, and 20 age- and sex-matched
      healthy control subjects underwent detailed physiologic testing, including tests
      of small airway function and a symptom-limited incremental cycle exercise test.
      RESULTS: Patients with CB (mean +/- SD postbronchodilator FEV1, 93% +/- 12%
      predicted) had greater chronic activity-related dyspnea, poorer health-related
      quality of life, and reduced habitual physical activity compared with patients
      without CB and control subjects (all P < .05). The degree of peripheral airway
      dysfunction and pulmonary gas trapping was comparable in both patient groups.
      Peak oxygen uptake was similarly reduced in patients with CB and those without
      compared with control subjects (% predicted +/- SD, 70 +/- 26, 71 +/- 29 and 106
      +/- 43, respectively), but those with CB had higher exertional dyspnea ratings
      and greater respiratory mechanical constraints at a standardized work rate than
      patients without CB (P < .05). CONCLUSIONS: Patients with CB reported greater
      chronic dyspnea and activity restriction than patients without CB and with
      similar mild airway obstruction. The CB group had greater dynamic respiratory
      mechanical impairment and dyspnea during exercise than patients without CB, which
      may help explain some differences in important patient-centered outcomes between
      the groups.

PMID- 25393127
TI  - Biofortified orange maize enhances beta-cryptoxanthin concentrations in egg yolks
      of laying hens better than tangerine peel fortificant.
AB  - The xanthophyll beta-cryptoxanthin provides vitamin A and has other purported
      health benefits. Laying hens deposit xanthophyll carotenoids into egg yolk. Hens
      (n = 8/group) were fed conventional-bred high beta-cryptoxanthin biofortified
      (orange) maize, tangerine peel-fortified white maize, lutein-fortified yellow
      maize, or white maize for 40 d to investigate yolk color changes using L*a*b*
      scales, yolk carotenoid enhancement, and hen vitamin A status. Yolks from hens
      fed orange maize had scores indicating a darker, orange color and mean higher
      beta-cryptoxanthin, zeaxanthin, and beta-carotene concentrations (8.43 +/- 1.82,
      23.1 +/- 4.8, 0.16 +/- 0.08 nmol/g, respectively) than other treatments (P <
      0.0001). Yolk retinol concentrations (mean: 14.4 +/- 3.42 nmol/g) were similar
      among groups and decreased with time (P < 0.0001). Hens fed orange maize had
      higher liver retinol (0.53 +/- 0.20 MUmol/g liver) than other groups (P <
      0.0001). beta-Cryptoxanthin-biofortified eggs could be another choice for
      consumers, providing enhanced color through a provitamin A carotenoid and
      supporting eggs' status as a functional food. 

PMID- 25393130
TI  - Cold temperature and biodiesel fuel effects on speciated emissions of volatile
      organic compounds from diesel trucks.
AB  - Speciated volatile organic compounds (VOCs) were measured in diesel exhaust from
      three heavy-duty trucks equipped with modern aftertreatment technologies.
      Emissions testing was conducted on a chassis dynamometer at two ambient
      temperatures (-7 and 22  degrees C) operating on two fuels (ultra low sulfur
      diesel and 20% soy biodiesel blend) over three driving cycles: cold start, warm
      start and heavy-duty urban dynamometer driving cycle. VOCs were measured
      separately for each drive cycle. Carbonyls such as formaldehyde and acetaldehyde
      dominated VOC emissions, making up ~ 72% of the sum of the speciated VOC
      emissions (?VOCs) overall. Biodiesel use led to minor reductions in aromatics and
      variable changes in carbonyls. Cold temperature and cold start conditions caused
      dramatic enhancements in VOC emissions, mostly carbonyls, compared to the warmer
      temperature and other drive cycles, respectively. Different 2007+ aftertreatment
      technologies involving catalyst regeneration led to significant modifications of
      VOC emissions that were compound-specific and highly dependent on test
      conditions. A comparison of this work with emission rates from different diesel
      engines under various test conditions showed that these newer technologies
      resulted in lower emission rates of aromatic compounds. However, emissions of
      other toxic partial combustion products such as carbonyls were not reduced in the
      modern diesel vehicles tested.

PMID- 25393131
TI  - General practitioners' knowledge, practices, and obstacles in the diagnosis and
      management of dementia.
AB  - OBJECTIVES: To identify general practitioners' (GPs) knowledge, practices, and
      obstacles with regard to the diagnosis and management of dementia. METHODS:
      Standardized questionnaires covering knowledge, practices, and obstacles were
      distributed among a purposive sample of GPs in Kathmandu, Nepal. Three hundred
      and eighty GPs responded (response rate = 89%). RESULTS: Knowledge of
      practitioners' with regard to the diagnosis and management of dementia was
      unsatisfactory (<50%). Diagnosis and management barriers are presented with
      regard to GP, patient, and carer factors. Specifically, the results address the
      following issues: communicating the diagnosis, negative views of dementia,
      difficulty diagnosing early-stage dementia, acceptability of specialists,
      responsibility for extra issues, knowledge of dementia and aging, less awareness
      of declining abilities, diminished resources to handle care, lack of specific
      guidelines, and poor awareness of epidemiology. CONCLUSIONS: Demographic changes
      mean that dementia will represent a significant problem in the future. The
      following paper outlines the problems and solutions that the Nepalese medical
      community needs to adopt to deal effectively with diagnosis, care, and management
      of dementia.

PMID- 25393132
TI  - A heteroleptic push-pull substituted iron(II) bis(tridentate) complex with low
      energy charge-transfer states.
AB  - A heteroleptic iron(II) complex [Fe(dcpp)(ddpd)](2+) with a strongly electron
      withdrawing ligand (dcpp, 2,6-bis(2-carboxypyridyl)pyridine) and a strongly
      electron-donating tridentate tripyridine ligand (ddpd, N,N'-dimethyl-N,N'
      dipyridine-2-yl-pyridine-2,6-diamine) is reported. Both ligands form six-membered
      chelate rings with the iron center, inducing a strong ligand field. This results
      in a high-energy, high-spin state ((5) T2 , (t2g )(4) (eg *)(2) ) and a low-spin
      ground state ((1) A1 , (t2g )(6) (eg *)(0) ). The intermediate triplet spin state
      ((3) T1 , (t2g )(5) (eg *)(1) ) is suggested to be between these states on the
      basis of the rapid dynamics after photoexcitation. The low-energy pi(*) orbitals
      of dcpp allow low-energy MLCT absorption plus additional low-energy LL'CT
      absorptions from ddpd to dcpp. The directional charge-transfer character is
      probed by electrochemical and optical analyses, Mobetabauer spectroscopy, and EPR
      spectroscopy of the adjacent redox states [Fe(dcpp)(ddpd)](3+) and
      [Fe(dcpp)(ddpd)](+) , augmented by density functional calculations. The combined
      effect of push-pull substitution and the strong ligand field paves the way for
      long-lived charge-transfer states in iron(II) complexes. 

PMID- 25393133
TI  - The Relationship Between Perceived Stress and Telomere Length: A Meta-analysis.
AB  - Telomeres protect the ends of chromosomes, and short telomere length is
      associated with poor health and mortality. This study reports a meta-analytic
      investigation of the relationship between perceived stress and telomere length,
      including results from eight studies with a total of 1143 participants. A meta
      analytic effect size of r = -0.25, p < 0.001, indicated that higher levels of
      perceived stress were associated with shorter telomere length. Examination of the
      studies for moderators of effect size identified some significant moderators,
      such as a difference in effect sizes between samples comprised of only women and
      mixed-sex samples. These results are only suggestive as they are based on a small
      set of studies, and funnel plot analyses indicated a publication bias. A
      significant relationship between more perceived stress and shorter telomere
      length is consistent with theoretical frameworks positing that stress induces
      physiological changes that result in shortened telomeres. Copyright (c) 2014 John
      Wiley & Sons, Ltd.

PMID- 25393129
TI  - Diabetes eye screening in urban settings serving minority populations: detection
      of diabetic retinopathy and other ocular findings using telemedicine.
AB  - IMPORTANCE: The use of a nonmydriatic camera for retinal imaging combined with
      the remote evaluation of images at a telemedicine reading center has been
      advanced as a strategy for diabetic retinopathy (DR) screening, particularly
      among patients with diabetes mellitus from ethnic/racial minority populations
      with low utilization of eye care. OBJECTIVE: To examine the rate and types of DR
      identified through a telemedicine screening program using a nonmydriatic camera,
      as well as the rate of other ocular findings. DESIGN, SETTING, AND PARTICIPANTS:
      A cross-sectional study (Innovative Network for Sight [INSIGHT]) was conducted at
      4 urban clinic or pharmacy settings in the United States serving predominantly
      ethnic/racial minority and uninsured persons with diabetes. Participants included
      persons aged 18 years or older who had type 1 or 2 diabetes mellitus and
      presented to the community-based settings. MAIN OUTCOMES AND MEASURES: The
      percentage of DR detection, including type of DR, and the percentage of detection
      of other ocular findings. RESULTS: A total of 1894 persons participated in the
      INSIGHT screening program across sites, with 21.7% having DR in at least 1 eye.
      The most common type of DR was background DR, which was present in 94.1% of all
      participants with DR. Almost half (44.2%) of the sample screened had ocular
      findings other than DR; 30.7% of the other ocular findings were cataract.
      CONCLUSIONS AND RELEVANCE: In a DR telemedicine screening program in urban clinic
      or pharmacy settings in the United States serving predominantly ethnic/racial
      minority populations, DR was identified on screening in approximately 1 in 5
      persons with diabetes. The vast majority of DR was background, indicating high
      public health potential for intervention in the earliest phases of DR when
      treatment can prevent vision loss. Other ocular conditions were detected at a
      high rate, a collateral benefit of DR screening programs that may be
      underappreciated.

PMID- 25393134
TI  - A moment of reflection.
AB  - Deborah Zimmermann, DNP, RN, Chair of the Commission on Magnet(r) Recognition,
      provides reflections regarding her 8 years on the Commission. Dr Zimmermann
      discusses how the standards have changed and how they have positively impacted
      nursing practice and patient outcomes. 

PMID- 25393135
TI  - Leading nursing through influence and structure: the system nurse executive role.
AB  - As health systems consolidate, the system chief nurse executive (SCNE) role is
      emerging as an important and strategic member of the health system leadership
      team. Based on a survey of incumbent SCNEs conducted by the American Organization
      of Nurse Executives (AONE), this article discusses the trends in this role
      including the structure and function in today's health systems. With the
      assistance of AONE, this group of leaders is creating a community of support and
      networking. Because of the broad influence of these roles, the SCNEs who serve in
      these roles are having a major influence on the practice of nursing in our
      nation's healthcare delivery system and clinical outcomes. 

PMID- 25393136
TI  - Nursing administration research: an evolving science.
AB  - The nature and focus of nursing administrative research have evolved over time.
      Recently, the research agenda has primarily reflected the national health policy
      agenda. Although nursing research has traditionally been dominated by clinical
      interests, nursing administrative research has historically addressed the
      interface of reimbursement, quality, and care delivery systems. This article
      traces the evolution of nursing administrative research to answer questions
      relevant to scope, practice, and policy and suggests future directions. 

PMID- 25393137
TI  - Postgraduate nurse practitioner training: what nurse executives need to know.
AB  - Nurse executives should be familiar with postgraduate nurse practitioner training
      programs. Supplemental training opportunities are gaining popularity across the
      country and are primarily funded by employers interested in recruiting and
      retaining qualified healthcare professionals. There is considerable variability
      in program learning objectives, clinical content, and titles used to describe
      participants' roles. This article offers program descriptions, associated costs,
      and a call for evidence of their impact on a growing constituent of the
      healthcare workforce. 

PMID- 25393138
TI  - Handle with care: the fragile nature of complex systems.

PMID- 25393139
TI  - Occupational stressors, stress perception levels, and coping styles of medical
      surgical RNs: a generational perspective.
AB  - OBJECTIVE: The purpose of this study was to compare the occupational stressors,
      the perceived stress levels, and coping styles of 3 generations of medical
      surgical (MS) nurses. BACKGROUND: The literature supports that the nurse's role
      is stressful based on a variety of factors including physical labor, human
      suffering, work hours, staffing, and interpersonal relationships. Data indicate
      that there are generational differences in the response to stress. The 3
      predominant nursing generations coexisting in the nursing workforce add to the
      complexity of the recognition and coping skills to address stress. METHODS: A
      correlational design was used. A convenience sample of MS nurses participated in
      this study by completing 4 questionnaires. RESULTS: Occupational stressors were
      found to be significant predictors for perceived stress among all generations of
      nurses in this sample. Also, the higher the level of stress perception among
      nurses, the higher the use of coping behaviors. Generation Y reported a higher
      level of perceived stress and higher use of escape avoidance coping behaviors,
      while baby boomers reported higher use of self-controlling coping behaviors.
      CONCLUSIONS: By identifying the needs of each of the generational cohorts, nurse
      leaders, nurse educators, and policy makers can better assist the nursing
      workforce to remain at the bedside, improve patient outcomes, and maintain a
      positive work environment.

PMID- 25393140
TI  - Clinical ethics residency for nurses: an education model to decrease moral
      distress and strengthen nurse retention in acute care.
AB  - The experience of unaddressed moral distress can lead to nurse attrition and/or
      distancing from patients, compromising patient care. Nurses who are confident in
      their ethical decision making abilities and moral agency have the antidote to
      moral distress for themselves and their colleagues and can act as local or
      institutional ethics resources. We describe a grant-funded model education
      program designed to increase ethics competence throughout the institution. 

PMID- 25393141
TI  - Evaluation of a toolkit to assist with implementation of the "80/20"
      recommendation.
AB  - OBJECTIVES: This project developed and evaluated a toolkit for use by nurse
      executives in New York State (NYS) hospitals in implementing the recommendation
      that 80% of the registered nursing workforce be prepared with a BSN by 2020.
      BACKGROUND: While the literature substantiates the link between BSN preparation
      for RNs and enhanced patient outcomes, few resources exist to assist nurse
      executives in increasing their proportion of BSN-prepared RNs. METHODS: Seven NYS
      nurse executives received the toolkit electronically and evaluated the efficacy
      of the contents. RESULTS: Nurse executives found the toolkit beneficial and
      shared it inside and outside their organizations. CONCLUSIONS: The toolkit was
      considered a valuable resource in increasing the proportion of BSN-prepared RNs
      in these organizations.

PMID- 25393142
TI  - Supporting a healthy culture: results of the Practice Environment Scale,
      Australia in a Magnet(r) designated hospital.
AB  - The Magnet Recognition Program(r) requires evidence that nursing practice
      environments support staff to provide optimal care, access professional
      development opportunities, and participate in hospital affairs. The research
      presented in this article aimed to assess clinical nurses' work environment at a
      recently designated, private Magnet(r) hospital in Sydney, Australia. Authors
      compare results with baseline data collected for a gap analysis before
      application for recognition. The outcomes challenge previously reported data
      suggesting that hospitals on the journey to Magnet recognition outperform already
      designated hospitals in this respect. 

PMID- 25393143
TI  - New graduate nurse transition programs and clinical leadership skills in novice
      RNs.
AB  - OBJECTIVE: The objective of this study was to determine predictors of clinical
      leadership skill (CLS) for RNs with 24 months of clinical experience or less.
      BACKGROUND: New graduate nurse transition programs (NGNTPs) have been proposed as
      a strategy to increase CLS. CLS is associated with positive patient outcomes.
      METHOD: Method used was hierarchical regression modeling to evaluate predictors
      of CLS among individual characteristics of RNs and characteristics of NGNTPs.
      RESULTS: Perceived overall quality of an NGNTP was the strongest predictor of CLS
      (R = 0.041, P < .01). Clinical experience and NGNTP characteristics accounted for
      6.9% of the variance in CLS and 12.6% of the variance among RNs with assigned
      mentors (P < .01). RNs participating in NGNTPs for more than 24 weeks were 21
      times more likely to remain employed within the organization when compared with
      NGNTPs of 12 weeks or less, a significant cost-benefit to the organization.
      CONCLUSION: Although perceived overall quality of a NGNTP was the strongest
      predictor of CLS, much of the variance in CLS remains unexplained.

PMID- 25393144
TI  - Nursing leadership education: an innovative executive solution.
AB  - As nursing leaders retire from the nursing workforce, too few nurses are
      preparing to replace them. The barriers to obtaining the educational credentials
      necessary to take this important step in a leadership career can appear
      insurmountable because of cost and time restraints. The authors present an
      executive format master of science program whose delivery method and content
      align with the professional and personal needs of emerging nurse leaders. 

PMID- 25393146
TI  - Stratified community responses to methane and sulfate supplies in mud volcano
      deposits: insights from an in vitro experiment.
AB  - Numerous studies on marine prokaryotic communities have postulated that a process
      of anaerobic oxidation of methane (AOM) coupled with sulfate reduction (SR) is
      the main methane sink in the world's oceans. AOM has also been reported in the
      deep biosphere. But the responses of the primary microbial players in eliciting
      changes in geochemical environments, specifically in methane and sulfate
      supplies, have yet to be fully elucidated. Marine mud volcanoes (MVs) expel a
      complex fluid mixture of which methane is the primary component, forming an
      environment in which AOM is a common phenomenon. In this context, we attempted to
      identify how the prokaryotic community would respond to changes in methane and
      sulfate intensities, which often occur in MV environments in the form of
      eruptions, diffusions or seepage. We applied an integrated approach, including
      (i) biochemical surveys of pore water originated from MV, (ii) in vitro
      incubation of mud breccia, and (iii) prokaryotic community structure analysis.
      Two distinct AOM regions were clearly detected. One is related to the sulfate
      methane transition zone (SMTZ) at depth of 30-55 cm below the sea floor (bsf);
      the second is at 165-205 cm bsf with ten times higher rates of AOM and SR. This
      finding contrasts with the sulfide concentrations in pore waters and supports the
      suggestion that potential AOM activity below the SMTZ might be an important
      methane sink that is largely ignored or underestimated in oceanic methane budget
      calculations. Moreover, the incubation conditions below the SMTZ favor the growth
      of methanotrophic archaeal group ANME-2 compared to ANME-1, and promote the rapid
      growth and high diversity of bacterial communities. These incubation conditions
      also promote the increase of richness in bacterial communities. Our results
      provide direct evidence of the mechanisms by which deep AOM processes can affect
      carbon cycling in the deep biosphere and global methane biochemistry. 

PMID- 25393147
TI  - Multi-level modeling of light-induced stomatal opening offers new insights into
      its regulation by drought.
AB  - Plant guard cells gate CO2 uptake and transpirational water loss through stomatal
      pores. As a result of decades of experimental investigation, there is an
      abundance of information on the involvement of specific proteins and secondary
      messengers in the regulation of stomatal movements and on the pairwise
      relationships between guard cell components. We constructed a multi-level dynamic
      model of guard cell signal transduction during light-induced stomatal opening and
      of the effect of the plant hormone abscisic acid (ABA) on this process. The model
      integrates into a coherent network the direct and indirect biological evidence
      regarding the regulation of seventy components implicated in stomatal opening.
      Analysis of this signal transduction network identified robust cross-talk between
      blue light and ABA, in which [Ca2+]c plays a key role, and indicated an absence
      of cross-talk between red light and ABA. The dynamic model captured more than
      10(31) distinct states for the system and yielded outcomes that were in
      qualitative agreement with a wide variety of previous experimental results. We
      obtained novel model predictions by simulating single component knockout
      phenotypes. We found that under white light or blue light, over 60%, and under
      red light, over 90% of all simulated knockouts had similar opening responses as
      wild type, showing that the system is robust against single node loss. The model
      revealed an open question concerning the effect of ABA on red light-induced
      stomatal opening. We experimentally showed that ABA is able to inhibit red light
      induced stomatal opening, and our model offers possible hypotheses for the
      underlying mechanism, which point to potential future experiments. Our modelling
      methodology combines simplicity and flexibility with dynamic richness, making it
      well suited for a wide class of biological regulatory systems.

PMID- 25393149
TI  - Involvement of MEK/ERK1/2 and PI3K/Akt pathways in the refractory behavior of
      GH3B6 pituitary tumor cells to the inhibitory effect of TGFbeta1.
AB  - Pituitary tumor cells have a poor response to the growth inhibitory effect of
      TGFbeta1, possibly resulting from the cross talk of TGFbeta/Smads signal with
      other signaling pathways, an undescribed mechanism in these tumoral cells. To
      address this hypothesis, we investigated whether the mitogen-activated
      extracellular signal-regulated kinase (MEK)/ERK1/2 and phosphoinositide-3
      kinase/protein kinase B (PI3K/Akt) pathways were able to regulate the
      antimitogenic effect of TGFbeta1 on GH3B6 cells. TGFbeta1 treatment decreased the
      cell proliferation and induced an activation of mothers against decapentaplegic
      homolog 2/3 (Smad2/3), effects that were potentiated by MEK and PI3K inhibitors,
      thus indicating the existence of a cross talk between TGFbeta1/Smad with the
      MEK/ERK1/2 or PI3K/Akt pathways. In addition, through immunoprecipitation assays,
      a direct interaction was observed between Smad2/3-ERK1/2 and Smad2/3-Akt, which
      decreased when the GH3B6 cells were incubated with TGFbeta1 in the presence of
      MEK or PI3K inhibitors, thereby suggesting that the ERK1/2- and Akt-activated
      states were involved. These Smad2/3-ERK1/2 and Smad2/3-Akt associations were also
      confirmed by confocal and transmission electron microscopy. These findings
      indicate that the TGFbeta1-antimitogenic effect in GH3B6 cells was attenuated by
      the MEK/ERK1/2 and PI3K/Akt pathways via modulating Smad2/3 phosphorylation. This
      molecular mechanism could explain in part the refractory behavior of pituitary
      tumor cells to the inhibitory effect of TGFbeta1.

PMID- 25393148
TI  - Combined inhibition of monoacylglycerol lipase and cyclooxygenases
      synergistically reduces neuropathic pain in mice.
AB  - BACKGROUND AND PURPOSE: Neuropathic pain is commonly treated with GABA analogues,
      steroids or non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit one or
      more COX isozymes but chronic COX inhibition paradoxically increases
      gastrointestinal inflammation and risk of unwanted cardiovascular events. The
      cannabinoids also have analgesic and anti-inflammatory properties and reduce
      neuropathic pain in animal models. The present study investigated the analgesic
      effects of inhibiting both monoacylglycerol lipase (MAGL) and COX enzymes, using
      low doses of both inhibitors. EXPERIMENTAL APPROACH: Mice subjected to chronic
      constriction injury (CCI) were tested for mechanical and cold allodynia after
      administration of the MAGL inhibitor, JZL184, or the non-selective COX inhibitor
      diclofenac. Then, both drugs were co-administered at fixed dose proportions of
      1:3, 1:1 and 3:1, based on their ED50 values. PGs, endocannabinoids and related
      lipids were quantified in lumbar spinal cord. KEY RESULTS: Combining low doses of
      JZL184 and diclofenac synergistically attenuated mechanical allodynia and
      additively reduced cold allodynia. The cannabinoid CB1 receptor antagonist,
      rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the analgesic
      effects of the JZL184 and diclofenac combination on mechanical allodynia,
      implying that CB1 receptors were primarily responsible for the anti-allodynia.
      Diclofenac alone and with JZL184 significantly reduced PGE2 and PGF2alpha in
      lumbar spinal cord tissue, whereas JZL184 alone caused significant increases in
      the endocannabinoid metabolite, N-arachidonoyl glycine. CONCLUSIONS AND
      IMPLICATIONS: Combining COX and MAGL inhibition is a promising therapeutic
      approach for reducing neuropathic pain with minimal side effects.

PMID- 25393150
TI  - Geometric morphometrics for the taxonomy of 11 species of Anopheles
      (Nyssorhynchus) mosquitoes.
AB  - The subgenus Anopheles (Nyssorhynchus) (Diptera: Culicidae) includes the primary
      vectors of Plasmodium spp. in Colombia. Most adult females of this subgenus are
      difficult to identify in the field using the available keys. With the objective
      of further investigating the discriminatory power of modern morphometrics, both
      landmark-based and outline-based approaches were explored using the wing venation
      geometry of 11 Anopheles (Nyssorhynchus) species. Wing shape was able to separate
      the closest species of the subgenus. When the 11 species were analysed together,
      validated classification scores on average 5.3-8.6 times higher than those
      expected by chance were observed. These scores computed from the total sample of
      11 species were not satisfactory for the recognition of Anopheles benarrochi B,
      Anopheles oswaldoi s.l. and Anopheles strodei. These sibling species were
      captured in sympatry. To improve the identification power of the morphometric
      tool, it was necessary to analyse these species separately from the remaining
      species. The best classification scores were obtained using a combination of 12
      landmarks collected not only on the intersections of wing veins, but also on
      spots. An outline approach also gave excellent reclassification scores. Another
      pair of sibling species, collected in allopatry, Anopheles nuneztovari and
      Anopheles rangeli, also showed high classification scores. 

PMID- 25393151
TI  - In situ generation of electron acceptor for photoelectrochemical biosensing via
      hemin-mediated catalytic reaction.
AB  - A novel photoelectrochemical sensing strategy is designed for DNA detection on
      the basis of in situ generation of an electron acceptor via the catalytic
      reaction of hemin toward H2O2. The photoelectrochemical platform was established
      by sequential assembly of near-infrared CdTe quantum dots, capture DNA, and a
      hemin-labeled DNA probe to form a triple-helix molecular beacon (THMB) structure
      on an indium tin oxide electrode. According to the highly catalytic capacity of
      hemin toward H2O2, a photoelectrochemical mechanism was then proposed, in which
      the electron acceptor of O2 was in situ-generated on the electrode surface,
      leading to the enhancement of the photocurrent response. The utilization of CdTe
      QDs can extend the absorption edge to the near-infrared band, resulting in an
      increase in the light-to-electricity efficiency. After introducing target DNA,
      the THMB structure is disassembled and releases hemin and, thus, quenches the
      photocurrent. Under optimized conditions, this biosensor shows high sensitivity
      with a linear range from 1 to 1000 pM and detection limit of 0.8 pM. Moreover, it
      exhibits good performance of excellent selectivity, high stability, and
      acceptable fabrication reproducibility. This present strategy opens an
      alternative avenue for photoelectrochemical signal transduction and expands the
      applications of hemin-based materials in photoelectrochemical biosensing and
      clinical diagnosis. 

PMID- 25393152
TI  - Detection of induced mutations in CaFAD2 genes by next-generation sequencing
      leading to the production of improved oil composition in Crambe abyssinica.
AB  - Crambe abyssinica is a hexaploid oil crop for industrial applications. An
      increase of erucic acid (C22:1) and reduction of polyunsaturated fatty acid
      (PUFA) contents in crambe oil is a valuable improvement. An increase in oleic
      acid (C18:1), a reduction in PUFA and possibly an increase in C22:1 can be
      obtained by down-regulating the expression of fatty acid desaturase2 genes
      (CaFAD2), which code for the enzyme that converts C18:1 into C18:2. We conducted
      EMS-mutagenesis in crambe, followed by Illumina sequencing, to screen mutations
      in three expressed CaFAD2 genes. Two novel analysis strategies were used to
      detect mutation sites. In the first strategy, mutation detection targeted
      specific sequence motifs. In the second strategy, every nucleotide position in a
      CaFAD2 fragment was tested for the presence of mutations. Seventeen novel
      mutations were detected in 1100 one-dimensional pools (11 000 individuals) in
      three expressed CaFAD2 genes, including non-sense mutations and mis-sense
      mutations in CaFAD2-C1, -C2 and -C3. The homozygous non-sense mutants for CaFAD2
      C3 resulted in a 25% higher content of C18:1 and 25% lower content of PUFA
      compared to the wild type. The mis-sense mutations only led to small changes in
      oil composition. Concluding, targeted mutation detection using NGS in a polyploid
      was successfully applied and it was found that a non-sense mutation in even a
      single CaFAD2 gene can lead to changes in crambe oil composition. Stacking the
      mutations in different CaFAD2 may gain additional changes in C18:1 and PUFA
      contents. 

PMID- 25393153
TI  - Intermediate long-term clinical performance of dental implants placed in sites
      with a previous early implant failure: a retrospective analysis.
AB  - PURPOSE: The aim of this retrospective case-control study was to evaluate the
      intermediate long-term clinical performance and success rate of dental implants
      inserted into sites of previous early implant failure. MATERIAL AND METHODS: A
      retrospective evaluation was conducted on 6456 patients with 10,234 implants from
      January 2004 to December 2011. The patients with early implant failure retreated
      in previous failed sites were enrolled in the study. The collected data included
      patient's characteristics, implants characteristics (failed and replaced), and if
      was the case, any additional surgery performed prior or at the same of implant
      placement to obtain proper hard tissues dimensions. Moreover, peri-implant
      clinical parameters, marginal bone loss (MBL), and the implant quality scale
      (IQS) of the replacement implants were recorded after delivering of the final
      prosthesis and annually thereafter. RESULTS: Ninety-six patients (100 implants)
      showed initial early failure (failure rate = 0.98%). Sixty-six patients (male:
      38; female: 28; mean age: 42.3 +/- 18.2 years old) with early implant failure
      received a total of 67 replacement dental implants. Three patients with three
      implants dropped out of the study during the mean follow-up of 69.4 +/- 27.0
      months. The implant length and diameter were varied for seven sites. The number
      of sites that required additional surgeries increased from 18 to 24 for first and
      replacement implant insertion, respectively. One of the 67 replacement implants
      failed before prosthesis delivery, and one implant failure occurred 20 months
      after prosthesis delivery, which represented a cumulative survival rate of 94.6%.
      At last follow-up evaluation, the overall mean MBL was 1.7 +/- 1.3 mm. Two of 64
      implants failed according to IQS criteria, three implants showed satisfactory
      survival, and one implant showed compromised survival. No pain or tenderness was
      observed in the rest 58 implants evaluated, showing a success rate (optimum
      health) of 90.6%. CONCLUSION: Within the limits of the present study, early
      implant failure was not an obstacle for implant replacement at the same site
      after an adequate soft and hard tissues healing period.

PMID- 25393154
TI  - Synthesis and spectroscopic characterization of high-spin mononuclear iron(II) p
      semiquinonate complexes.
AB  - Two mononuclear iron(II) p-semiquinonate (pSQ) complexes have been generated via
      one-electron reduction of precursor complexes containing a substituted 1,4
      naphthoquinone ligand. Detailed spectroscopic and computational analysis
      confirmed the presence of a coordinated pSQ radical ferromagnetically coupled to
      the high-spin Fe(II) center. The complexes are intended to model electronic
      interactions between (semi)quinone and iron cofactors in biology. 

PMID- 25393155
TI  - Impact of tert-butyl alcohol on crystallization kinetics of gemcitabine
      hydrochloride in frozen aqueous solutions.
AB  - The effect of tert-butyl alcohol (TBA) on isothermal crystallization kinetics of
      gemcitabine hydrochloride (GHCl) in frozen aqueous solutions was assessed by cold
      stage microscopy. Addition of TBA (0%-5%, w/w) increased the value of Johnson
      Mehl-Avrami rate constant (1.3-33.3 h-1) and reduced the Avrami exponent (2.5
      1.0). Thermodynamic parameters [enthalpy (DeltaH(?)), entropy (DeltaS(?)), and
      free energy (DeltaG(?)) of activation], calculated using Arrhenius and Eyring
      Polanyi equations, established that TBA (2%, w/w) accelerated GHCl
      crystallization by reducing its DeltaH(?) (53.9 cf. 96.5 kJ/mol-1) and DeltaG(?)
      (68.5 cf. 74.9 kJ/mol-1). Further, to explore insights into the effect of TBA on
      nucleation and crystal growth of GHCl, crystallization kinetics data were
      deconvolved using Finke-Watzky model. This revealed that addition of TBA
      decreased DeltaH(?) of nucleation and increased DeltaS(?) of crystal growth,
      thereby reducing DeltaG(?) of nucleation and crystal growth by 11.7% and 4.2%,
      respectively. Finkey-Watzky model also predicted a reduction in the crystal size
      upon TBA addition, which was confirmed by comparing particle size of GHCl
      lyophilized in the presence and absence of TBA. In conclusion, TBA reduces
      DeltaG(?) of nucleation and crystal growth in a differential manner, thereby
      enhancing the crystallization kinetics of GHCl and affecting its morphological
      features.

PMID- 25393156
TI  - Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) side effects often prompt dose reduction
      or discontinuation, and this MMF dose reduction (MDR) can lead to rejection and
      possibly graft loss. Unfortunately, little is known about what factors might
      cause or contribute to MDR. Frailty, a measure of physiologic reserve, is
      emerging as an important, novel domain of risk in kidney transplantation
      recipients. We hypothesized that frailty, an inflammatory phenotype, might be
      associated with MDR. METHODS: We measured frailty (shrinking, weakness,
      exhaustion, low physical activity, and slowed walking speed), other patient and
      donor characteristics, longitudinal MMF doses, and graft loss in 525 kidney
      transplantation recipients. Time-to-MDR was quantified using an adjusted Cox
      proportional hazards model. RESULTS: By 2 years after transplantation, 54% of
      frail recipients and 45% of nonfrail recipients experienced MDR; by 4 years,
      incidence was 67% and 51%. Frail recipients were 1.29 times (95% confidence
      interval [95% CI], 1.01-1.66; P = 0.04) more likely to experience MDR, as were
      deceased donor recipients (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.44-2.54,
      P < 0.001) and older adults (age >= 65 vs <65; aHR, 1.47; 95% CI, 1.10-1.96, P =
      0.01). Mycophenolate mofetil dose reduction was independently associated with a
      substantially increased risk of death-censored graft loss (aHR, 5.24; 95% CI,
      1.97-13.98, P = 0.001). CONCLUSION: A better understanding of risk factors for
      MMF intolerance might help in planning alternate strategies to maintain adequate
      immunosuppression and prolong allograft survival.

PMID- 25393157
TI  - Impact of Procedure-Related Complications on Long-term Islet Transplantation
      Outcome.
AB  - BACKGROUND: Pancreatic islet transplantation offers a promising biotherapy for
      the treatment of type 1 diabetes, but this procedure has met significant
      challenges over the years. One such challenge is to address why primary graft
      function still remains inconsistent after islet transplantation. Several
      variables have been shown to affect graft function, but the impact of procedure
      related complications on primary and long-term graft functions has not yet been
      explored. METHODS: Twenty-six patients with established type 1 diabetes were
      included in this study. Each patient had two to three intraportal islet infusions
      to obtain 10,000 islet equivalent (IEQ)/kg in body weight, equaling a total of 68
      islet infusions. Islet transplantation consisted of three sequential fresh islet
      infusions within 3 months. Islet infusions were performed surgically or under
      ultrasound guidance, depending on patient morphology, availability of the
      radiology suite, and patient medical history. Prospective assessment of adverse
      events was recorded and graded using "Common Terminology Criteria for adverse
      events in Trials of Adult Pancreatic Islet Transplantation." RESULTS: There were
      no deaths or patients dropouts. Early complications occurred in nine of 68
      procedures. beta score 1 month after the last graft and optimal graft function
      (beta score >=7) rate were significantly lower in cases of procedure-related
      complications (P = 0.02, P = 0.03). Procedure-related complications negatively
      impacted graft function (P = 0.009) and was an independent predictive factor of
      long-term graft survival (P = 0.033) in multivariate analysis. CONCLUSION:
      Complications occurring during radiologic or surgical intraportal islet
      transplantation significantly impair primary graft function and graft survival
      regardless of their severity.

PMID- 25393158
TI  - Safety events in kidney transplant recipients: results from the folic Acid for
      vascular outcome reduction in transplant trial.
AB  - BACKGROUND: Kidney transplant recipients are at increased risk for adverse safety
      events related to their reduced renal function and many medications. METHODS: We
      determined the incidence of adverse safety events based on previously defined
      Agency for Healthcare and Research Quality (AHRQ) International Classification of
      Diseases-9 (ICD-9) code-derived patient safety indicators (PSI) in the Folic Acid
      for Vascular Outcome Reduction in Transplant trial participants who had a
      hospitalization stratified by tertiles of estimated glomerular filtration rate
      (GFR). We also examined the frequency of Micromedex defined two precautionary
      drug-drug interactions, and two medications whose use may be contraindicated
      because of reduced GFR from the Folic Acid for Vascular Outcome Reduction in
      Transplant trial medication thesaurus at baseline, and annually among 4,110
      participants. Logistic regression was used to examine the relationship between
      patient safety events and baseline demographic and clinical variables at a
      participant level. Event rates were estimated at participant and visit levels.
      RESULTS: Of the 2,514 patients with a hospitalization, 978 (38.9%) experienced an
      AHRQ PSI. Factors which were associated with more common AHRQ PSI included: U.S.
      location, history of cardiovascular disease or diabetes, and lower tertile of
      estimated GFR. At a participant level, 2,524 of the 4,110 participants (61.4%)
      were taking calcineurin inhibitor and statin, 378 (9.2%) were taking azathioprine
      and an angiotensin-converting enzyme inhibitor, 171 (12.9%) were taking a
      sulfonylurea), 45 (3.4%) were taking metformin despite a baseline GFR below 40 mL
      per min per 1.73 m. CONCLUSION: We conclude that patient safety events are not
      uncommon in kidney transplant recipients. Careful monitoring is necessary to
      prevent adverse outcomes.

PMID- 25393159
TI  - Urinary Urea Excretion and Long-term Outcome After Renal Transplantation.
AB  - BACKGROUND: Little is known about optimal protein intake after transplantation.
      The aim of this study was to prospectively investigate associations of urinary
      urea excretion, a marker for protein intake, with graft failure and mortality in
      renal transplant recipients (RTR) and potential effect modification by body mass
      index (BMI) and estimated glomerular filtration rate (eGFR). METHODS: Urinary
      urea excretion was measured in repeated 24-hr urine collections between 6 and 18
      months after transplantation. RESULTS: In total, 940 RTR were included. During
      4.4 (2.3-7.8) years of follow-up for graft failure and 4.8 (2.5-8.3) years for
      all-cause mortality, 78 RTR developed graft failure and 158 RTR died. Urinary
      urea excretion was not associated with graft failure in the overall population,
      but was inversely associated with graft failure in RTR with BMI less than 25 kg/m
      (hazard ratio [HR], 0.64 [0.28-1.50] and 0.27 [0.09-0.83] for the second and
      third tertiles, respectively, P < 0.001), and in RTR with eGFR of 45 mL per min
      per 1.73 m or higher (HR, 0.34 [0.15-0.79], P = 0.015 and HR, 0.31 [0.11-0.86], P
      = 0.025 for the second and third tertiles, respectively), both independent of
      potential confounders. Compared to the first tertile, RTR in the second and third
      tertiles of urinary urea excretion were at a lower risk of all-cause mortality
      (HR, 0.47 [0.32-0.69]; P < 0.001 and HR, 0.42 [0.26-0.68]; P < 0.001,
      respectively), independent of potential confounders. Body mass index and eGFR did
      not influence this association. CONCLUSION: Urinary urea excretion, a marker for
      protein intake, was inversely related to graft failure in RTR with BMI less than
      25 kg/m and in RTR with an eGFR of 45 mL per min per 1.73 m or higher. In
      addition, urinary urea excretion was inversely related to mortality.

PMID- 25393160
TI  - Prevalence and risk factors of noncontrolled and resistant arterial hypertension
      in renal transplant recipients.
AB  - BACKGROUND: Arterial hypertension (HT) is common in renal transplant recipients
      (RTRs). Control of HT is not optimal in this high-risk population despite
      recommendations for target blood pressure levels under 130/80 mm Hg. METHODS: We
      performed a cross-sectional analysis of the prevalence of uncontrolled HT, and
      using a Cox regression model, we identified the risk factors associated with
      resistant HT. RESULTS: Eight hundred eleven RTRs (>1 year after transplantation)
      were included. A total of 10.5% were normotensive (<130/80 mm Hg without
      treatment), 41% had controlled HT, 32.5% uncontrolled HT, and 16% resistant HT.
      In univariate analysis, compared to controlled HT, the RH group had significantly
      higher body mass index and older donors, delayed graft function, prevalence of
      metabolic syndrome (69.2 vs. 51.9%), fast glycemia and glycated hemoglobin,
      albuminuria, triglycerides and uric acid levels, and worse measured glomerular
      filtration rate (mGFR). In multivariate analysis, recipient age (P < 0,001), mGFR
      (P = 0.037), albuminuria (P < 0.001), and metabolic syndrome (P = 0.007) were
      significantly associated with RH. Association of metabolic syndrome with RH was
      much stronger than each of its components. CONCLUSION: Our data show that despite
      the recommendations issued by scientific societies, blood pressure control in
      RTRs is far from the recommended targets. At least a third of our patients
      (uncontrolled HT) did not receive optimal treatment and suffered therapeutic
      inertia. Decreased mGFR, metabolic syndrome, and urinary albumin excretion
      emerged as strong predictors of poor HT control. Whether prevention and
      management of the metabolic syndrome and reduction of albuminuria could help to
      more consistently reach the blood pressure recommended targets deserves further
      investigation.

PMID- 25393161
TI  - Predictors of success for pulmonary rehabilitation in patients awaiting lung
      transplantation.
AB  - BACKGROUND: Numerous studies have shown the effectiveness of comprehensive
      pulmonary rehabilitation (PR) programs in chronic obstructive pulmonary disease
      (COPD). At present, it is uncertain whether PR is also effective in the
      management of patients with various diseases awaiting lung transplantation (LTx).
      METHODS: In a retrospective clinical preanalysis and postanalysis, we
      investigated the effects of a 5-week inpatient PR in LTx candidates. We compared
      data of patients with COPD, alpha-1-antitrypsin deficiency, interstitial lung
      disease, or cystic fibrosis before and after PR with regard to exercise capacity
      (6-min walking distance [6MWD]) and health-related quality of life (HRQL; SF36).
      Multivariate stepwise regression analysis was performed to detect predictors of
      PR outcome. RESULTS: Eight hundred eleven data sets from consecutive patients
      referred to our PR center before LTx could be analysed (COPD, 360; alpha-1
      antitrypsin deficiency, 127; interstitial lung disease, 195; cystic fibrosis, 69;
      other, 60). After PR 6MWD increased by 56 +/- 58 m (P < 0.001), the physical
      summary component of SF36 (0-100) improved by 1.9 +/- 8.5 points (P < 0.001), the
      mental summary component of SF36 by 8.7 +/- 13.5 points (P < 0.001). Stepwise
      regression analysis yielded no relevant predictors of success or nonsuccess of PR
      with regard to age, sex, disease, body mass index, 6MWD, and HRQL on admission.
      CONCLUSION: Short-term comprehensive PR can significantly improve exercise
      capacity and HRQL in LTx candidates to a clinically relevant extent independent
      of the underlying lung disease. No relevant predictor influencing PR outcome
      could be detected. Further research is needed to evaluate the relevance of PR
      before LTx and its impact on clinical outcome after transplantation.

PMID- 25393162
TI  - Notch affects the prodifferentiating effect of retinoic acid and PMA on leukemic
      cells.
AB  - Notch proteins determine cell fate decisions in the development of diverse
      tissues. Notch has been initially found in T-ALL but its role has been also
      studied in myelopoiesis and myeloid leukemias. Studies in different model systems
      have led to a widespread controversy as to whether Notch promotes or blocks
      myeloid differentiation. In this work, we evaluated the influence of Notch
      activation on leukemic cell differentiation along the monocytic and myelocytic
      pathway induced by phorbol 12-myristate 13-acetate (PMA) or all-trans retinoic
      acid (ATRA). We observed that differentiation of the human myeloblastic cell line
      HL-60 can be retarded or blocked by Delta/Notch interaction. ATRA induces
      complete remission in patients with acute promyelocytic leukemia, but it cannot
      completely eliminate the leukemic clone and to be effective it should be combined
      with chemotherapy. Our findings suggest that Notch signaling may contribute to
      the incomplete elimination of the leukemic cells after PMA or ATRA treatment and
      the blockage of Notch pathway may be beneficial in the treatment of myeloid
      leukemia. (c) 2014 International Society for Advancement of Cytometry. 

PMID- 25393163
TI  - Bacterial community dynamics of salted and fermented shrimp based on denaturing
      gradient gel electrophoresis.
AB  - The Korean traditional seafood jeotgal is consumed directly or as an additive in
      other foods to improve flavor or fermentation efficiency. Saeujot, made from
      salted and fermented tiny shrimp (SFS; Acetes japonicus), is the best-selling
      jeotgal in Korea. In this study, we reveal the microbial diversity and dynamics
      in naturally fermented shrimp by denaturing gradient gel electrophoresis (DGGE).
      The population fingerprints of the predominant microbiota and its succession were
      generated by DGGE analysis of universal V3 16S rDNA polymerase chain reaction
      (PCR) amplicons. Overall, 17 strains were identified from sequencing of 30 DGGE
      bands. The DGGE profiles showed diverse bacterial populations in the sample,
      throughout the fermentation of SFS. Staphylococcus equorum, Halanaerobium
      saccharolyticum, Salimicrobium luteum, and Halomonas jeotgali were the dominant
      bacteria, and their levels steadily increased during the fermentation process.
      Certain other bacteria, such as Psychrobacter jeotgali and Halomonas alimentaria
      appeared during the early-fermentation process, while Alkalibacterium
      putridalgicola, Tetragenococcus muriaticus, and Salinicoccus jeotgali appeared
      during the late-fermentation process. The members of the order Bacillales were
      found to be predominant during the fermentation of SFS. Furthermore, S. equorum
      was identified as the dominant bacterial isolate by the traditional method of
      culturing under aerobic and facultative anaerobic conditions. We expect that this
      information will facilitate the design of autochthonous starter cultures for the
      production of SFS with desired characteristic sensory profiles and shorter
      ripening times. 

PMID- 25393164
TI  - The effect of high-power ultrasound and gas phase plasma treatment on Aspergillus
      spp. and Penicillium spp. count in pure culture.
AB  - AIMS: The aim of this study was to investigate and compare two nonthermal
      techniques in the inactivation of moulds. METHODS AND RESULTS: High power
      ultrasound (20 kHz) and nonthermal gas phase plasma treatments were studied in
      the inactivation of selected moulds. Aspergillus spp. and Penicillium spp. were
      chosen as the most common mould present in or on food. Experimental design was
      introduced to establish and optimize working variables. For high power
      ultrasound, the greatest reduction of moulds (indicated by the total removal of
      viable cells) was obtained after ultrasound treatments at 60 degrees C
      (thermosonication) for 6 and 9 min (power applied, 20-39 W). For plasma
      treatment, the greatest inactivation of moulds was observed for the longest
      treatment time (5 min) and lowest sample volume (2 ml), (AP12, AP13, PP12 and
      PP13). CONCLUSIONS: The great amount of applied energy required for achieving a
      partial log reduction in viable cells is the limiting factor for using high-power
      ultrasound. However, both treatment methods could be combined in the future to
      produce beneficial outcomes. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      deals with nonthermal food processing techniques and the results and findings
      present in this study are the root for further prospective studies. The food
      industry is looking for nonthermal methods that will enable food preservation,
      reduce deterioration of food compounds and structure and prolong food shelf life.

PMID- 25393165
TI  - Endogenous motilin, but not ghrelin plasma levels fluctuate in accordance with
      gastric phase III activity of the migrating motor complex in man.
AB  - BACKGROUND: Fluctuations in motilin plasma levels have been implicated in the
      control of the migrating motor complex (MMC). A plasma peak of motilin is present
      before a gastric phase III. Furthermore, not only exogenous administration of
      motilin but also ghrelin induces a gastric phase III in man. Aim of this study
      was to investigate the role of endogenous ghrelin in the regulation of the MMC.
      METHODS: Plasma samples for motilin and ghrelin were taken in between two
      consecutive phases III of either origin measured using high-resolution manometry.
      KEY RESULTS: The duration of 1 complete MMC cycle was on average 95 +/- 12 min.
      Sixty percent of the first phases III and 40% of the second phases III had a
      gastric origin (p = 0.0574). Motilin (p < 0.05) plasma levels differed
      significantly between the phases of the MMC but total and octanoylated ghrelin
      did not. The percentage change in motilin during the MMC was dependent on the
      origin of phase III (p < 0.05). Motilin levels increased on average with 35 +/-
      10% right before a gastric phase III and with 3 +/- 4% before a duodenal phase
      III (p < 0.05). The percentage change in total and octanoylated ghrelin plasma
      levels was not affected by the origin of phase III. CONCLUSIONS & INFERENCES:
      These results confirm the role of motilin but not of ghrelin as an endogenous
      physiological regulator of the MMC with a gastric phase III.

PMID- 25393166
TI  - Rumors and Realities: Making Sense of HIV/AIDS Conspiracy Narratives and
      Contemporary Legends.
AB  - The social context of the early HIV/AIDS epidemic in the United States provided
      fertile ground for rumors about transmission. Today, however, rumors about
      HIV/AIDS persist only within the African American public. Focus group and public
      discourse data reveal the content and distribution of HIV/AIDS origin and
      conspiracy rumors. Rumor and contemporary legend theory allows reinterpretation
      of rumors as a measure of trust between the African American public and health
      professionals, not as evidence of ignorance or of historical racial oppression.
      To improve public health results in the African American community, HIV/AIDS
      efforts must acknowledge the sources and meanings of rumors, include rumors as a
      measure of trust, and address the underlying distrust that the rumors signify.

PMID- 25393167
TI  - Montez and Zajacova Respond.

PMID- 25393168
TI  - Systematic Review of Prevalence of Young Child Overweight and Obesity in the
      United States-Affiliated Pacific Region Compared With the 48 Contiguous States:
      The Children's Healthy Living Program.
AB  - We estimated overweight and obesity (OWOB) prevalence of children in US
      Affiliated Pacific jurisdictions (USAP) of the Children's Healthy Living Program
      compared with the contiguous United States. We searched peer-reviewed literature
      and government reports (January 2001-April 2014) for OWOB prevalence of children
      aged 2 to 8 years in the USAP and found 24 sources. We used 3 articles from
      National Health and Nutrition Examination Surveys for comparison. Mixed models
      regressed OWOB prevalence on an age polynomial to compare trends (n = 246 data
      points). In the USAP, OWOB prevalence estimates increased with age, from 21% at
      age 2 years to 39% at age 8 years, increasing markedly at age 5 years; the
      proportion obese increased from 10% at age 2 years to 23% at age 8 years. The
      highest prevalence was in American Samoa and Guam.

PMID- 25393169
TI  - Identifying Key Priorities for Future Palliative Care Research Using an
      Innovative Analytic Approach.
AB  - Using an innovative approach, we identified research priorities in palliative
      care to guide future research initiatives. We searched 7 databases (2005-2012)
      for review articles published on the topics of palliative and hospice-end-of-life
      care. The identified research recommendations (n = 648) fell into 2 distinct
      categories: (1) ways to improve methodological approaches and (2) specific topic
      areas in need of future study. The most commonly cited priority within the theme
      of methodological approaches was the need for enhanced rigor. Specific topics in
      need of future study included perspectives and needs of patients, relatives, and
      providers; underrepresented populations; decision-making; cost-effectiveness;
      provider education; spirituality; service use; and interdisciplinary approaches
      to delivering palliative care. This review underscores the need for additional
      research on specific topics and methodologically rigorous research to inform
      health policy and practice.

PMID- 25393170
TI  - Life Expectancy and Education.

PMID- 25393171
TI  - Community Mobilization to Reduce Drug Use, Quang Ninh, Vietnam.
AB  - Objectives. We implemented an intervention to reduce drug use in an urban commune
      in northern Vietnam. Methods. We encouraged the intervention commune to accept
      responsibility for developing their own intervention strategies based on a
      community mobilization model used in southern, rural China. We selected a
      comparison commune, which had demographic characteristics and a drug history
      similar to the intervention commune. The 2-year incidence of new drug users was
      estimated retrospectively in the intervention and comparison communes between
      baseline (2003) and follow-up (2009). Results. Increased incidence of new
      (noninjecting) drug users between 2003 and 2009 in the intervention commune was
      lower than that in the comparison commune, and these participants expressed more
      positive attitudes toward local authority and people with drug use and HIV/AIDS.
      Increased condom use during last intercourse with female sex workers and with
      female casual partners was observed in the intervention commune. HIV prevalence
      and positive opioid tests decreased more in the intervention commune.
      Conclusions. Our results suggested that the community mobilization had a positive
      influence in the intervention commune.

PMID- 25393173
TI  - Clinical Preventive Services Coverage and the Affordable Care Act.
AB  - The Affordable Care Act requires many health plans to provide coverage for
      certain recommended clinical preventive services without charging copays or
      deductible payments. This provision could lead to greater uptake of many services
      that can improve health and save lives. Although the coverage provision is broad,
      there are many caveats that also apply. It is important for providers and public
      health professionals to understand the nuances of the coverage rules to help
      maximize their potential to improve population health.

PMID- 25393172
TI  - Financial incentives for abstinence among socioeconomically disadvantaged
      individuals in smoking cessation treatment.
AB  - OBJECTIVES: We evaluated the effectiveness of offering adjunctive financial
      incentives for abstinence (contingency management [CM]) within a safety net
      hospital smoking cessation program. METHODS: We randomized participants (n = 146)
      from a Dallas County, Texas, Tobacco Cessation Clinic from 2011 to 2013 to usual
      care (UC; cessation program; n = 71) or CM (UC + 4 weeks of financial incentives;
      n = 75), and followed from 1 week before the quit date through 4 weeks after the
      quit date. A subset (n = 128) was asked to attend a visit 12 weeks after the
      scheduled quit date. RESULTS: Participants were primarily Black (62.3%) or White
      (28.1%) and female (57.5%). Most participants were uninsured (52.1%) and had an
      annual household income of less than $12 000 (55.5%). Abstinence rates were
      significantly higher for those assigned to CM than UC at all visits following the
      quit date (all Ps < .05). Point prevalence abstinence rates in the CM and UC
      groups were 49.3% versus 25.4% at 4 weeks after the quit date and 32.8% versus
      14.1% at 12 weeks after the quit date. CM participants earned an average of
      $63.40 ($150 possible) for abstinence during the first 4 weeks after the
      scheduled quit date. CONCLUSIONS: Offering small financial incentives for
      abstinence might be an effective means to improve abstinence rates among
      socioeconomically disadvantaged individuals participating in smoking cessation
      treatment.

PMID- 25393174
TI  - HIV/AIDS in Puerto Rican People Who Inject Drugs: Policy Considerations.

PMID- 25393175
TI  - Evaluating a Large-Scale Community-Based Intervention to Improve Pregnancy and
      Newborn Health Among the Rural Poor in India.
AB  - Objectives. We evaluated the effectiveness of the Sure Start project, which was
      implemented in 7 districts of Uttar Pradesh, India, to improve maternal and
      newborn health. Methods. Interventions were implemented at 2 randomly assigned
      levels of intensity. Forty percent of the areas received a more intense
      intervention, including community-level meetings with expectant mothers. A
      baseline survey consisted of 12 000 women who completed pregnancy in 2007; a
      follow-up survey was conducted for women in 2010 in the same villages. Our
      quantitative analyses provide an account of the project's impact. Results. We
      observed significant health improvements in both intervention areas over time; in
      the more intensive intervention areas, we found greater improvements in care
      seeking and healthy behaviors. The more intensive intervention areas did not
      experience a significantly greater decline in neonatal mortality. Conclusions.
      This study demonstrates that community-based efforts, especially mothers' group
      meetings designed to increase care-seeking and healthy behaviors, are effective
      and can be implemented at large scale.

PMID- 25393176
TI  - Unprotected Anal Intercourse With Casual Male Partners in Urban Gay, Bisexual,
      and Other Men Who Have Sex With Men.
AB  - Objectives. We investigated trends in, and predictors of, unprotected anal
      intercourse (UAI) with casual male partners of gay, bisexual, and other men who
      have sex with men (GBMSM). Methods. We analyzed data from cross-sectional
      intercept surveys conducted annually (2003-2008) at 2 large lesbian, gay, and
      bisexual community events in New York City. Survey data covered GBMSM's highest
      risk behaviors for HIV acquisition (HIV-negative or unknown status GBMSM, any
      UAI) and transmission (HIV-positive GBMSM, any serodiscordant unprotected UAI).
      Results. Across years, 32.3% to 51.5% of the HIV-negative or unknown status men
      endorsed any UAI, and 36.9% to 52.9% of the HIV-positive men endorsed
      serodiscordant UAI. We observed a few statistically significant fluctuations in
      engagement in high-risk behavior. However, these do not appear to constitute
      meaningful trends. Similarly, in some years, one or another demographic predictor
      of UAI was significant. Across years, however, no reliable pattern emerged.
      Conclusions. A significant proportion of urban GBMSM engage in high-risk sex,
      regardless of serostatus. No consistent demographic predictors emerged, implying
      a need for broad-based interventions that target all GBMSM.

PMID- 25393177
TI  - Disparities in Weight and Weight Behaviors by Sexual Orientation in College
      Students.
AB  - Objectives. We assessed disparities in weight and weight-related behaviors among
      college students by sexual orientation and gender. Methods. We performed cross
      sectional analyses of pooled annual data (2007-2011; n = 33 907) from students
      participating in a Minnesota state-based survey of 40 two- and four-year colleges
      and universities. Sexual orientation included heterosexual, gay or lesbian,
      bisexual, unsure, and discordant heterosexual (heterosexuals engaging in same-sex
      sexual experiences). Dependent variables included weight status (derived from
      self-reported weight and height), diet (fruits, vegetables, soda, fast food,
      restaurant meals, breakfast), physical activity, screen time, unhealthy weight
      control, and body satisfaction. Results. Bisexual and lesbian women were more
      likely to be obese than heterosexual and discordant heterosexual women. Bisexual
      women were at high risk for unhealthy weight, diet, physical activity, and weight
      control behaviors. Gay and bisexual men exhibited poor activity patterns, though
      gay men consumed significantly less regular soda (and significantly more diet
      soda) than heterosexual men. Conclusions. We observed disparities in weight-,
      diet-, and physical activity-related factors across sexual orientation among
      college youths. Additional research is needed to better understand these
      disparities and the most appropriate intervention strategies to address them.

PMID- 25393178
TI  - Human Papillomavirus Vaccination Among Young Adult Gay and Bisexual Men in the
      United States.
AB  - Objectives. We examined human papillomavirus (HPV) vaccination among gay and
      bisexual men, a population with high rates of HPV infection and HPV-related
      disease. Methods. A national sample of gay and bisexual men aged 18 to 26 years
      (n = 428) completed online surveys in fall 2013. We identified correlates of HPV
      vaccination using multivariate logistic regression. Results. Overall, 13% of
      participants had received any doses of the HPV vaccine. About 83% who had
      received a health care provider recommendation for vaccination were vaccinated,
      compared with only 5% without a recommendation (P < .001). Vaccination was lower
      among participants who perceived greater barriers to getting vaccinated (odds
      ratio [OR] = 0.46; 95% confidence interval [CI] = 0.27, 0.78). Vaccination was
      higher among participants with higher levels of worry about getting HPV-related
      disease (OR = 1.54; 95% CI =  1.05, 2.27) or perceived positive social norms of
      HPV vaccination (OR = 1.57; 95% CI =  1.02, 2.43). Conclusions. HPV vaccine
      coverage is low among gay and bisexual men in the United States. Future efforts
      should focus on increasing provider recommendation for vaccination and should
      target other modifiable factors.

PMID- 25393180
TI  - Survey of US Correctional Institutions for Routine HCV Testing.
AB  - To ascertain HCV testing practices among US prisons and jails, we conducted a
      survey study in 2012, consisting of medical directors of all US state prisons and
      40 of the largest US jails, that demonstrated a minority of US prisons and jails
      conduct routine HCV testing. Routine voluntary HCV testing in correctional
      facilities is urgently needed to increase diagnosis, enable risk-reduction
      counseling and preventive health care, and facilitate evaluation for antiviral
      treatment.

PMID- 25393179
TI  - Predictors of Tobacco Use Among New York State Addiction Treatment Patients.
AB  - Objectives. We used admissions data from the New York State addiction treatment
      system to assess patient self-reported tobacco use and factors associated with
      tobacco use. Methods. We compared prevalence of tobacco use in the state
      addiction treatment system with that of a national sample of people receiving
      addiction treatment and with that of the New York general population in 2005 to
      2008. A random effects logistic model assessed relationships between patient- and
      program-level variables and tobacco use. Results. Prevalence of tobacco use in
      the New York treatment system was similar to that in national addiction treatment
      data and was 3 to 4 times higher than that in the general population. Co
      occurring mental illness, opiate use, methadone treatment, and being a child of a
      substance-abusing parent were associated with higher rates of tobacco use.
      Conclusions. We call on federal leadership to build capacity to address tobacco
      use in addiction treatment, and we call on state leadership to implement tobacco
      free grounds policies in addiction treatment systems.

PMID- 25393181
TI  - Disparities in tuberculosis burden among South Asians living in New York City,
      2001-2010.
AB  - OBJECTIVES: We have described the characteristics of South Asian-born
      tuberculosis (TB) patients living in New York City (NYC) and compared them with
      other foreign-born patients to explore possible explanations for the
      disproportionate burden of TB in the South Asian population. METHODS: We used
      data on demographic and clinical characteristics for TB patients identified by
      the NYC Bureau of Tuberculosis Control from 2001 to 2010 to compare South Asian
      patients with other Asian and other foreign-born patients. We reviewed genotyping
      and cluster investigation data for South Asian patients to assess the extent of
      genotype clustering and the possibility of local transmission in this population.
      RESULTS: The observed disparity in TB rates and burden among South Asians was not
      explained by social or clinical characteristics. A large amount of TB strain
      diversity was observed among South Asians, and they were less likely than other
      foreign-born patients to be infected with the same TB strain as another NYC
      patient. CONCLUSIONS: The majority of South Asians were likely infected with TB
      abroad. South Asians represent a meaningful foreign-born subpopulation for
      targeted detection and treatment of TB infection in NYC.

PMID- 25393182
TI  - A Framework for Enhancing the Value of Research for Dissemination and
      Implementation.
AB  - A comprehensive guide that identifies critical evaluation and reporting elements
      necessary to move research into practice is needed. We propose a framework that
      highlights the domains required to enhance the value of dissemination and
      implementation research for end users. We emphasize the importance of transparent
      reporting on the planning phase of research in addition to delivery, evaluation,
      and long-term outcomes. We highlight key topics for which well-established
      reporting and assessment tools are underused (e.g., cost of intervention,
      implementation strategy, adoption) and where such tools are inadequate or lacking
      (e.g., context, sustainability, evolution) within the context of existing
      reporting guidelines. Consistent evaluation of and reporting on these issues with
      standardized approaches would enhance the value of research for practitioners and
      decision-makers.

PMID- 25393184
TI  - Enhancing the Quality of Prevention Research Supported by the National Institutes
      of Health.
AB  - As the nation's premier biomedical research agency, the National Institutes of
      Health (NIH) has supported most of the research that underlies the prevention
      services that are provided to citizens in the United States and around the world.
      Within the NIH, the Office of Disease Prevention (ODP) has as its mission to
      improve the public health by increasing the scope, quality, dissemination, and
      effect of prevention research supported by the NIH. In today's environment, the
      ODP needs to focus its efforts to address this mission. To do so, the ODP has
      developed a strategic plan for 2014 to 2018. We provide background on the ODP and
      key points from the strategic plan.

PMID- 25393185
TI  - Public Health and Solitary Confinement in the United States.
AB  - The history of solitary confinement in the United States stretches from the
      silent prisons of 200 years ago to today's supermax prisons, mechanized
      panopticons that isolate tens of thousands, sometimes for decades. We examined
      the living conditions and characteristics of the populations in solitary
      confinement. As part of the growing movement for reform, public health agencies
      have an ethical obligation to help address the excessive use of solitary
      confinement in jails and prisons in accordance with established public health
      functions (e.g., violence prevention, health equity, surveillance, and minimizing
      of occupational and psychological hazards for correctional staff). Public health
      professionals should lead efforts to replace reliance on this overly punitive
      correctional policy with models based on rehabilitation and restorative justice.

PMID- 25393183
TI  - Asian American problem drinking trajectories during the transition to adulthood:
      ethnic drinking cultures and neighborhood contexts.
AB  - OBJECTIVES: We aimed to identify problem drinking trajectories and their
      predictors among Asian Americans transitioning from adolescence to adulthood. We
      considered cultural and socioeconomic contextual factors, specifically ethnic
      drinking cultures, neighborhood socioeconomic status, and neighborhood coethnic
      density, to identify subgroups at high risk for developing problematic drinking
      trajectories. METHODS: We used a sample of 1333 Asian Americans from 4 waves of
      the National Longitudinal Study of Adolescent to Adult Health (1994-2008) in
      growth mixture models to identify trajectory classes of frequent heavy episodic
      drinking and drunkenness. We fitted multinomial logistic regression models to
      identify predictors of trajectory class membership. RESULTS: Two dimensions of
      ethnic drinking culture-drinking prevalence and detrimental drinking pattern in
      the country of origin-were predictive of problematic heavy episodic drinking and
      drunkenness trajectories. Higher neighborhood socioeconomic status in adolescence
      was predictive of the trajectory class indicating increasing frequency of
      drunkenness. Neighborhood coethnic density was not predictive of trajectory class
      membership. CONCLUSIONS: Drinking cultures in the country of origin may have
      enduring effects on drinking among Asian Americans. Further research on ethnic
      drinking cultures in the United States is warranted for prevention and
      intervention.

PMID- 25393186
TI  - Routine HIV Testing in Indiana Community Health Centers.
AB  - Objectives. We assessed routine HIV testing in Indiana community health centers
      (CHCs). Methods. CHC medical directors reported HIV services, testing behaviors,
      barriers, and health center characteristics via survey from April to May 2013.
      Standard of care testing was measured by the extent to which CHCs complied with
      national guidelines for routine HIV testing in clinical settings. Results. Most
      (85.7%) CHCs reported HIV testing, primarily at patient request or if the patient
      was symptomatic. Routine HIV testing was provided for pregnant women by 60.7% of
      CHCs. Only 10.7% provided routine testing for adolescents to adults up to age 65
      years. Routine testing was reported by 14.3% for gay and bisexual men, although
      46.4% of CHCs reported asking patients about sexual orientation. Linkage to care
      services for HIV-positive patients, counseling for HIV treatment adherence, and
      partner testing generally was not provided. Conclusions. Most CHCs reported HIV
      testing, but such testing did not reflect the standard of care, because it
      depended on patient request or symptoms. One approach in future studies may be to
      allow respondents to compare current testing with standard of care and then
      reflect on barriers to and facilitators of adoption and implementation of routine
      HIV testing.

PMID- 25393187
TI  - Legal Authority for Infectious Disease Reporting in the United States: Case Study
      of the 2009 H1N1 Influenza Pandemic.
AB  - Tracking of infectious diseases is a public health core function essential to
      disease prevention and control. Each state mandates reporting of certain
      infectious diseases to public health authorities. These laws vary by state, and
      the variation could affect the ability to collect critical information. The 2009
      H1N1 influenza pandemic served as a case study to examine the legal authority in
      the 50 states; Washington, DC; and New York City for mandatory infectious disease
      reporting, particularly for influenza and new or emerging infectious diseases.
      Our study showed reporting laws to be generally present and functioning well;
      nevertheless, jurisdictions should be mindful of their mandated parameters and
      review the robustness of their laws before they face a new or emerging disease
      outbreak.

PMID- 25393188
TI  - Prospective Associations Among Assets and Successful Transition to Early
      Adulthood.
AB  - Objectives. We investigated prospective associations among assets (e.g., family
      communication), which research has shown to protect youths from risk behavior,
      and successful transition to early adulthood (STEA). Methods. We included
      participants (n = 651) aged 18 years and older at study wave 5 (2007-2008) of the
      Youth Asset Study, in the Oklahoma City, Oklahoma, metro area, in the analyses.
      We categorized 14 assets into individual-, family-, or community-level groups. We
      included asset groups assessed at wave 1 (2003-2004) in linear regression
      analyses to predict STEA 4 years later at wave 5. Results. Individual- and
      community-level assets significantly (P < .05) predicted STEA 4 years later and
      the associations were generally linear, indicating that the more assets
      participants possessed the better the STEA outcome. There was a gender
      interaction for family-level assets suggesting that family-level assets were
      significant predictors of STEA for males but not for females. Conclusions. Public
      health programming should focus on community- and family-level youth assets as
      well as individual-level youth assets to promote positive health outcomes in
      early adulthood.

PMID- 25393189
TI  - Inside Maine's Medicine Cabinet: Findings From the Drug Enforcement
      Administration's Medication Take-Back Events.
AB  - Objectives. We evaluated the quantity and type of medications obtained in unused
      medications return programs and the proportion of medication waste. Methods. We
      analyzed data collected in 11 Maine cities in 2011 to 2013 during 6 Drug
      Enforcement Administration (DEA) national medication take-back events. Pharmacy
      doctoral student volunteers collected data under the supervision of law
      enforcement, independent of the DEA. Data entry into the Pharmaceutical
      Collection Monitoring System, through its interface with Micromedex, allowed for
      analysis of medication classification, controlled substance category, therapeutic
      class, and percentage of medication waste (units returned/units dispensed).
      Results. Medication take-back events resulted in return of 13 599 individual
      medications from 1049 participants. We cataloged 553 019 units (capsules,
      tablets, milliliters, patches, or grams), representing 69.7% medication waste.
      Noncontrolled prescription medications accounted for 56.4% of returns, followed
      by over-the-counter medications (31.4%) and controlled prescription medications
      (9.1%). Conclusions. The significant quantities of medications, including
      controlled substances, returned and high degree of medication waste emphasize the
      need for medication collection programs to further public health research and
      improve health in our communities.

PMID- 25393190
TI  - Variations in Asian Americans: How Neighborhood Concordance Is Associated With
      Health Care Access and Utilization.
AB  - We examined associations of different levels of same-ethnicity neighborhood
      concordance with health care access and utilization among all Asian American,
      Chinese, Filipino, and Vietnamese adults (aged 18-64 years) using the 2005, 2007,
      and 2009 California Health Interview Survey and the 2010 US Census. Although
      associations varied by subgroup, Asian Americans in highly concordant
      neighborhoods were more likely to lack a usual source of care but did not lack
      doctor visits or experience delays in medical care and prescriptions.

PMID- 25393191
TI  - Social Competence and Obesity in Elementary School.
AB  - Objectives. We examined the relationship between children's weight and social
      competence. Methods. We used data from the third- and fifth-grade waves of the
      nationally representative Early Childhood Longitudinal Study, Kindergarten Class
      of 1998-1999 (n = 8346) to examine changes in children's weight and social
      competence. Results. Obesity in third grade was not associated with subsequent
      changes in social competence between third and fifth grade, but social competence
      in third grade was associated with subsequent development of obesity. Among
      normal-weight children, having higher social competence in third grade was
      associated with lower odds of becoming overweight (odds ratio [OR] = 0.80 +/
      0.09; P < .05) or obese (OR = 0.20 +/-0.08; P < .001). In addition, obese
      children with higher social competence were more likely to lose weight between
      third and fifth grade (OR = 1.43 +/-0.25; P < .05). Conclusions. Obesity and
      impaired social competence often occur together and have serious implications for
      children's well-being. More knowledge about how weight and social competence
      affect one another could inform interventions to promote children's social
      development and reduce obesity.

PMID- 25393192
TI  - Professional Societies, Political Action Committees, and Party Preferences.
AB  - Societies representing physician specialties and other health care personnel
      commonly have political action committees (PACs). These PACs seek to advance
      their members' interests through advocacy and campaign contributions. We examined
      contribution data for health care workers' PACs from the 2010 to 2012 election
      cycles and found that higher annual income was strongly associated with greater
      giving to Republican candidates. Patterns of giving may offer insights into
      various medical workers' party preferences, political leanings, and views of
      health care reform.

PMID- 25393193
TI  - Coupled Ethical-Epistemic Analysis of Public Health Research and Practice:
      Categorizing Variables to Improve Population Health and Equity.
AB  - The categorization of variables can stigmatize populations, which is ethically
      problematic and threatens the central purpose of public health: to improve
      population health and reduce health inequities. How social variables (e.g.,
      behavioral risks for HIV) are categorized can reinforce stigma and cause
      unintended harms to the populations practitioners and researchers strive to
      serve. Although debates about the validity or ethical consequences of
      epidemiological variables are familiar for specific variables (e.g., ethnicity),
      these issues apply more widely. We argue that these tensions and debates
      regarding epidemiological variables should be analyzed simultaneously as ethical
      and epistemic challenges. We describe a framework derived from the philosophy of
      science that may be usefully applied to public health, and we illustrate its
      application.

PMID- 25393194
TI  - Cognitive Dissonance in the Early Thirties: The League of Nations Health
      Organization Confronts the Worldwide Economic Depression.

PMID- 25393195
TI  - Cochran and Mays Respond.

PMID- 25393196
TI  - Assessing the Expected Impact of Global Health Treaties: Evidence From 90
      Quantitative Evaluations.
AB  - We assessed what impact can be expected from global health treaties on the basis
      of 90 quantitative evaluations of existing treaties on trade, finance, human
      rights, conflict, and the environment. It appears treaties consistently succeed
      in shaping economic matters and consistently fail in achieving social progress.
      There are at least 3 differences between these domains that point to design
      characteristics that new global health treaties can incorporate to achieve
      positive impact: (1) incentives for those with power to act on them; (2)
      institutions designed to bring edicts into effect; and (3) interests advocating
      their negotiation, adoption, ratification, and domestic implementation.
      Experimental and quasiexperimental evaluations of treaties would provide more
      information about what can be expected from this type of global intervention.

PMID- 25393197
TI  - End-of-Life Care in Critical Condition.

PMID- 25393198
TI  - Deren et al. Respond.

PMID- 25393199
TI  - Changing Gender Norms and Reducing Intimate Partner Violence: Results From a
      Quasi-Experimental Intervention Study With Young Men in Ethiopia.
AB  - Objectives. We assessed the effects of a community-based project in Ethiopia that
      worked with young men to promote gender-equitable norms and reductions in
      intimate partner violence (IPV). Methods. A quasi-experimental design was used to
      assign young Ethiopian men 15 to 24 years of age (809 participants were surveyed
      at baseline in 2008) to an intervention involving community engagement (CE)
      activities in combination with interactive group education (GE) sessions
      promoting gender-equitable norms and violence prevention, an intervention
      involving CE activities alone, or a comparison group. Results. Participants in
      the GE + CE intervention were twice as likely (P < .01) as those in the
      comparison group to show increased support for gender-equitable norms between the
      baseline and end-line points. Also, the percentage of GE + CE participants who
      reported IPV toward their partner in the preceding 6 months decreased from 53% to
      38% between baseline and end line, and the percentage in the CE-only group
      decreased from 60% to 37%; changes were negligible in the comparison group.
      Conclusions. Promoting gender equity is an important strategy to reduce IPV.

PMID- 25393201
TI  - Misclassification and Undersampling of Sexual Minorities in Population Surveys.

PMID- 25393200
TI  - The Collateral Damage of Mass Incarceration: Risk of Psychiatric Morbidity Among
      Nonincarcerated Residents of High-Incarceration Neighborhoods.
AB  - Objectives. We examined whether residence in neighborhoods with high levels of
      incarceration is associated with psychiatric morbidity among nonincarcerated
      community members. Methods. We linked zip code-linked information on neighborhood
      prison admissions rates to individual-level data on mental health from the
      Detroit Neighborhood Health Study (2008-2012), a prospective probability sample
      of predominantly Black individuals. Results. Controlling for individual- and
      neighborhood-level risk factors, individuals living in neighborhoods with high
      prison admission rates were more likely to meet criteria for a current (odds
      ratio [OR] = 2.9; 95% confidence interval [CI] = 1.7, 5.5) and lifetime (OR =
      2.5; 95% CI = 1.4, 4.6) major depressive disorder across the 3 waves of follow-up
      as well as current (OR = 2.1; 95% CI = 1.0, 4.2) and lifetime (OR = 2.3; 95% CI =
      1.2, 4.5) generalized anxiety disorder than were individuals living in
      neighborhoods with low prison admission rates. These relationships between
      neighborhood-level incarceration and mental health were comparable for
      individuals with and without a personal history of incarceration. Conclusions.
      Incarceration may exert collateral damage on the mental health of individuals
      living in high-incarceration neighborhoods, suggesting that the public mental
      health impact of mass incarceration extends beyond those who are incarcerated.

PMID- 25393202
TI  - Implementing an HIV Rapid Testing-Linkage-to-Care Project Among Homeless
      Individuals in Los Angeles County: A Collaborative Effort Between Federal,
      County, and City Government.
AB  - Objectives. We developed and implemented an HIV rapid testing-linkage-to-care
      initiative between federal and local government. Methods. We used mixed
      methodology; HIV testing data were collected on-site, and qualitative data were
      collected via telephone. We used postintervention stakeholder and staff
      interviews to evaluate barriers and facilitators to this initiative. Results. We
      tested 817 individuals. We identified and confirmed 7 preliminary HIV positive
      individuals (0.86% seropositivity), 5 of whom were linked to care. Mean testing
      cost was $48.95 per client; cost per positive result was $5714. Conclusions. This
      initiative can be used as a template for other health departments and research
      teams focusing on homelessness and mitigation of the HIV/AIDS epidemic.

PMID- 25393204
TI  - Generic concept to program the time domain of self-assemblies with a self
      regulation mechanism.
AB  - Nature regulates complex structures in space and time via feedback loops,
      kinetically controlled transformations, and under energy dissipation to allow non
      equilibrium processes. Although man-made static self-assemblies realize excellent
      control over hierarchical structures via molecular programming, managing their
      temporal destiny by self-regulation is a largely unsolved challenge. Herein, we
      introduce a generic concept to control the time domain by programming the
      lifetimes of switchable self-assemblies in closed systems. We conceive dormant
      deactivators that, in combination with fast promoters, enable a unique kinetic
      balance to establish an autonomously self-regulating, transient pH-state, whose
      duration can be programmed over orders of magnitude-from minutes to days.
      Coupling this non-equilibrium state to pH-switchable self-assemblies allows
      predicting their assembly/disassembly fate in time, similar to a precise self
      destruction mechanism. We demonstrate a platform approach by programming self
      assembly lifetimes of block copolymers, nanoparticles, and peptides, enabling
      dynamic materials with a self-regulation functionality. 

PMID- 25393205
TI  - Re: Alt C, Hampel F, Hallscheidt P, Sohn C, Schlehe B, Brocker K. 3T MRI-based
      measurements for the integrity of the female pelvic floor in 25 healthy
      nulliparous women. Neurourol Urodyn 2016;35:218-23.

PMID- 25393203
TI  - Antibiotic adjuvants: diverse strategies for controlling drug-resistant
      pathogens.
AB  - The growing number of bacterial pathogens that are resistant to numerous
      antibiotics is a cause for concern around the globe. There have been no new broad
      spectrum antibiotics developed in the last 40 years, and the drugs we have
      currently are quickly becoming ineffective. In this article, we explore a range
      of therapeutic strategies that could be employed in conjunction with antibiotics
      and may help to prolong the life span of these life-saving drugs. Discussed
      topics include antiresistance drugs, which are administered to potentiate the
      effects of current antimicrobials in bacteria where they are no longer (or never
      were) effective; antivirulence drugs, which are directed against bacterial
      virulence factors; host-directed therapies, which modulate the host's immune
      system to facilitate infection clearance; and alternative treatments, which
      include such therapies as oral rehydration for diarrhea, phage therapy, and
      probiotics. All of these avenues show promise for the treatment of bacterial
      infections and should be further investigated to explore their full potential in
      the face of a postantibiotic era. 

PMID- 25393206
TI  - Controlling the dynamics of cell transition in heterogeneous cultures using
      surface chemistry.
AB  - Developing materials that can preferentially select defined cancer cell
      populations for biological characterization will greatly enhance our
      understanding of cancer cell growth, differentiation, and invasion. The
      transitional events between epithelial and mesenchymal phenotypes are
      particularly crucial, as primary tumors and secondary metastasis are generally
      epithelial in nature, whereas circulating mesenchymal cells derived from primary
      epithelial cells appear to facilitate the spread of disease and its resistance to
      therapy. This study describes an amino-functionalized material, which promotes
      the enrichment of an epithelial phenotype from a single cell line containing both
      epithelial and mesenchymal subpopulations of cancer cells. The isolation and
      transitional control of such subpopulations using functional materials will
      advance understanding of the disease process, have a significant impact on the
      downstream development of new targeted cancer therapeutics, and also be
      applicable to tissue engineering and regenerative medicine. 

PMID- 25393207
TI  - Targeted delivery of vaccine to dendritic cells by chitosan nanoparticles
      conjugated with a targeting peptide ligand selected by phage display technique.
AB  - The paper presents a novel dendritic cells (DC)-targeting peptide, TPAFRYS (TP)
      identified by phage display technique and conjugated to chitosan in order to
      develop an efficient DC-targeting vaccine delivery carrier. TP-conjugated
      chitosan nanoparticles (TPC-NPs) were prepared with ovalbumin (OVA) as a model
      vaccine by ionic gelation. Flow cytometry and immunocytochemistry studies
      demonstrated the higher targeting ability of TPC-NPs to DCs in compared to
      chitosan NPs. Moreover, TPC-NPs exhibited higher targeting specificity in DCs
      than macrophage and myoblasts. Furthermore, immunization of mice with OVA-loaded
      TPC-NPs enhanced OVA-specific serum IgG and IgG isotype antibodies production.
      Thus, DC-targeting strategy demonstrates a potential approach to enhance the
      effectiveness of vaccines. 

PMID- 25393208
TI  - Primary skin closure after damage control laparotomy.
AB  - BACKGROUND: Damage control laparotomy (DCL) is used widely in the management of
      patients with traumatic injuries but carries significant morbidity. Surgical-site
      infection (SSI) also carries potential morbidity, increased costs and prolonged
      hospital stay. The aim of this study was to determine whether primary skin
      closure after DCL increases the risk of SSI. METHODS: This was a retrospective
      institutional review of injured patients undergoing DCL between 2004 and 2012.
      Outcomes of patients who had primary skin closure at the time of fascial closure
      were compared with those of patients whose skin wound was left open to heal by
      secondary intention. The association between skin closure and SSI was evaluated
      using propensity score-adjusted multivariable logistic regression. RESULTS: Of
      510 patients who underwent DCL, primary fascial closure was achieved in 301.
      Among these, 111 (36.9 per cent) underwent primary skin closure and in 190 (63.1
      per cent) the skin wound was left open. Fascial closure at the initial take-back
      surgery was associated with having skin closure (P < 0.001), and colonic injury
      was associated with leaving the skin open (P = 0.002). On multivariable analysis,
      primary skin closure was associated with an increased risk of abdominal SSI (P =
      0.020), but not fascial dehiscence (P = 0.446). Of patients receiving skin
      closure, 85.6 per cent did not develop abdominal SSI and were spared the
      morbidity of managing an open wound at discharge. CONCLUSION: Primary skin
      closure after DCL is appropriate but may be associated with an increased risk of
      SSI.

PMID- 25393209
TI  - The first free flaps and the problems they addressed.

PMID- 25393210
TI  - Chromosomal microarray in fetuses with increased nuchal translucency.
AB  - OBJECTIVE: To assess the clinical value of using high-resolution chromosomal
      microarray (CMA) for the examination of genomic imbalances in prenatal uncultured
      chorionic villus samples from fetuses with increased nuchal translucency (NT) and
      a normal quantitative fluorescent polymerase chain reaction (QF-PCR) result, in a
      clinical setting in which more than 95% of pregnant women receive first-trimester
      combined screening. METHODS: From January 2013 to July 2014, we included 132
      chorionic villus samples from consecutive ongoing pregnancies, with fetal NT >=
      3.5  mm at 11-13 weeks' gestation, from obstetric units (publicly funded
      healthcare) in Central and North Denmark Regions. DNA was extracted directly from
      the samples and examined with QF-PCR (n = 132) and 180 kb oligonucleotide array
      based comparative genomic hybridization (n =  94). RESULTS: In 38 cases,
      aneuploidies for chromosomes 18, 21 or X, or triploidy, were detected by QF-PCR.
      Among the 94 cases with a normal QF-PCR result, we detected pathogenic copy
      number variants (CNVs) by CMA in 12 fetuses (12.8% (95% CI, 7.5-21.0%)). In an
      additional three (3.2%) cases, CNVs with uncertain clinical significance were
      detected. CONCLUSION: CMA is a valuable diagnostic technique in pregnancies with
      isolated fetal NT >= 3.5 mm.

PMID- 25393211
TI  - Tracer tomography: design concepts and field experiments using heat as a tracer.
AB  - Numerical and laboratory studies have provided evidence that combining hydraulic
      tomography with tomographic tracer tests could improve the estimation of
      hydraulic conductivity compared with using hydraulic data alone. Field
      demonstrations, however, have been lacking so far, which we attribute to
      experimental difficulties. In this study, we present a conceptual design and
      experimental applications of tracer tomography at the field scale using heat as a
      tracer. In our experimental design, we improve active heat tracer testing by
      minimizing possible effects of heat losses, buoyancy, viscosity, and changing
      boundary conditions. We also utilize a cost-effective approach of measuring
      temperature changes in situ at high resolution. We apply the presented method to
      the 8 m thick heterogeneous, sandy gravel, alluvial aquifer at the Lauswiesen
      Hydrogeological Research Site in Tubingen, Germany. Results of our tomographic
      heat-tracer experiments are in line with earlier work on characterizing the
      aquifer at the test site. We demonstrate from the experimental perspective that
      tracer tomography is applicable and suitable at the field scale using heat as a
      tracer. The experimental results also demonstrate the potential of heat-tracer
      tomography as a cost-effective means for characterizing aquifer heterogeneity. 

PMID- 25393213
TI  - Public attitudes about different types of anti-bullying laws: results from a
      national survey.
AB  - State anti-bullying laws have been enacted across the United States to address
      bullying both by and of youths. Although these statutes can provide critical
      protection to youth, there is debate about whether such laws should enumerate
      protected classes of youth. Weight-based bullying is an increasingly prevalent
      form of harassment and it has been overlooked in policy initiatives. Enumeration
      in existing laws might help protect overweight victims. As no research has
      examined this issue, we conducted a national survey of American adults (N=1155)
      to assess public opinion about enactment of anti-bullying laws that vary
      according to whether or not they enumerate distinguishing characteristics. Our
      results demonstrated substantial public agreement (ranging from 2/3 to 3/4 of
      participants) with enactment of state and federal anti-bullying laws that
      enumerate distinguishing characteristics, including physical appearance and
      weight, which are currently absent in most statutes. Our evidence can inform
      policy and legal approaches to protect youth effectively from bullying. 

PMID- 25393212
TI  - Characterization of genotoxic response to 15 multiwalled carbon nanotubes with
      variable physicochemical properties including surface functionalizations in the
      FE1-Muta(TM) mouse lung epithelial cell line.
AB  - Carbon nanotubes vary greatly in physicochemical properties. We compared
      cytotoxic and genotoxic response to 15 multiwalled carbon nanotubes (MWCNT) with
      varying physicochemical properties to identify drivers of toxic responses. The
      studied MWCNT included OECD Working Party on Manufactured Nanomaterials (WPMN)
      (NM-401, NM-402, and NM-403), materials (NRCWE-026 and MWCNT-XNRI-7), and three
      sets of surface-modified MWCNT grouped by physical characteristics (thin, thick,
      and short I-III, respectively). Each Groups I-III included pristine, hydroxylated
      and carboxylated MWCNT. Group III also included an amino-functionalized MWCNT.
      The level of surface functionalization of the MWCNT was low. The level and type
      of elemental impurities of the MWCNT varied by <2% of the weight, with
      exceptions. Based on dynamic light scattering data, the MWCNT were well-dispersed
      in stock dispersion of nanopure water with 2% serum, but agglomerated and
      sedimented during exposure. FE1-Muta(TM) Mouse lung epithelial cells were exposed
      for 24 hr. The levels of DNA strand breaks (SB) were evaluated using the comet
      assay, a screening assay suitable for genotoxicity testing of nanomaterials.
      Exposure to MWCNT (12.5-200 ug/ml) did not induce significant cytotoxicity
      (viability above 92%). Cell proliferation was reduced in highest doses of some
      MWCNT after 24 hr, and was associated with generation of reactive oxygen species
      and high surface area. Increased levels of DNA SB were only observed for Group II
      consisting of MWCNT with large diameters and high Fe2 O3 and Ni content.
      Significantly, increased levels of SB were only observed at 200 ug/ml of MWCNT
      042. Overall, the MWCNT were not cytotoxic and weakly genotoxic after 24 hr
      exposure to doses up to 200 ug/ml.

PMID- 25393214
TI  - Shading the TRF2 recruiting function: a new horizon in drug development.
AB  - The shelterin protein TRF2 has come to the limelight for its role in telomere
      maintenance and tumorigenesis. Herein, the application of rational design and
      synthesis allowed identifying the first TRF2TRFH binder able to elicit a marked
      DNA damage response in cancer cells. This work paves the way for the
      unprecedented employment of a chemical tool to finely tune specific mechanisms
      underlying telomere maintenance. 

PMID- 25393215
TI  - Comparative effectiveness of [(18) F]-fluorocholine PET-CT and pelvic MRI with
      diffusion-weighted imaging for staging in patients with high-risk prostate
      cancer.
AB  - BACKGROUND: Accurate staging is important before surgical decision in patients
      with high-risk prostate cancer (PCa). The purpose of this study was to
      prospectively compare the diagnostic performance of (18) F-FCholine and MRI with
      diffusion weighted imaging (DWIMRI) for local and regional lymph node (LN)
      staging before radical prostatectomy (RP) with extended pelvic lymphadenectomy
      (PLND). METHODS: We identified 47 patients who underwent (18) F-FCholine and
      DWIMRI followed by surgical treatment (either prostatectomy or LN dissection or
      an association of prostatectomy and LN dissection) between May 2010 and December
      2012 at Bordeaux University Hospital. These patients were part of a prospective
      study (EudraCT number 2009-014839-21) evaluating the interest of (18) F-FCholine
      in staging of high-risk PCa. Diagnostic performances were retrospectively
      determined for each of (18) F-FCholine and DWIMRI considering LN invasion, each
      of prostate sextants, capsular invasion and extension to seminal vesicles. (18) F
      FCholine and MR findings were correlated with histological findings. RESULTS: In
      a region-based LN analysis, the sensitivity and positive predictive value
      specificity were respectively, 56% and 98% for (18) F-Choline, and 17% and 97%
      for DWIMRI. In a patient-based analysis the sensitivity and positive predictive
      value were respectively 78% and 94% for (18) F-Choline and 33% and 84% for DWIMRI
      (P = 0.015). For tumor staging, DWIMRI showed better performances with a better
      specificity (69%) for sextants analysis and sensitivity to detect seminal vesicle
      invasion (73% vs. 36%). CONCLUSIONS: (18) F-FCholine imaging appears to provide
      helpful additional information in the staging of high-risk PCa. It appears
      essential for predicting LN status due to its higher sensitivity and specificity
      for LN involvement. However, despite excellent performance, it cannot replace MRI
      that remains better for tumoral localization and local evaluation, especially for
      seminal vesicle invasion. PATIENT SUMMARY: This study highlights the interest of
      (18) F-Choline in the staging of high risk prostate cancer in addition with DWI
      MRI, especially so in the evaluation of lymph node involvement due to its high
      sensitivity and excellent specificity.

PMID- 25393216
TI  - Impact of abuse-deterrent OxyContin on prescription opioid utilization.
AB  - PURPOSE: We quantified the degree to which the August 2010 reformulation of abuse
      deterrent OxyContin affected its use, as well as the use of alternative extended
      release and immediate-release opioids. METHODS: We used the IMS Health National
      Prescription Audit, a nationally representative source of prescription activity
      in the USA, to conduct a segmented time-series analysis of the use of OxyContin
      and other prescription opioids. Our primary time period of interest was 12 months
      prior to and following August 2010. We performed model checks and sensitivity
      analyses, such as adjusting for marketing and promotion, using alternative lag
      periods, and adding extra observation points. RESULTS: OxyContin sales were
      similar before and after the August 2010 reformulation, with approximately 550
      000 monthly prescriptions. After adjusting for declines in the generic extended
      release oxycodone market, the formulation change was associated with a reduction
      of approximately 18 000 OxyContin prescription sales per month (p = 0.02). This
      decline corresponded to a change in the annual growth rate of OxyContin use, from
      4.9% prior to the reformulation to -23.8% during the year after the
      reformulation. There were no statistically significant changes associated with
      the sales of alternative extended-release (p = 0.42) or immediate-release (p =
      0.70) opioids. Multiple sensitivity analyses supported these findings and their
      substantive interpretation. CONCLUSIONS: The market debut of abuse-deterrent
      OxyContin was associated with declines in its use after accounting for the
      simultaneous contraction of the generic extended-release oxycodone market.
      Further scrutiny into the effect of abuse-deterrent formulations on medication
      use and health outcomes is vital given their popularity in opioid drug
      development.

PMID- 25393217
TI  - Triple phase dynamic computed tomographic perfusion characteristics of
      spirocercosis induced esophageal nodules in non-neoplastic versus neoplastic
      canine cases.
AB  - Neoplastic transformation of Spirocerca lupi induced esophageal nodules carries a
      poor prognosis. Clinical, clinicopathological, endoscopic, and radiographic
      characteristics may be indicative of neoplastic transformation but variable
      sensitivity and specificity of these parameters makes their use questionable. We
      hypothesized that CT would be a better diagnostic modality to discriminate
      between non-neoplastic and neoplastic nodules. In this prospective study of 38
      dogs, the appearance and perfusion characteristics of confirmed spirocercosis
      induced neoplastic and non-neoplastic esophageal nodules were described using
      survey CT and triple phase dynamic CT angiography (CTA). Pre- and post-contrast
      early arterial, late arterial, and venous CTA images were evaluated. Non
      neoplastic nodules were smooth and nonmineralized with a higher proportion of
      hypoattenuating necropurulent cavities compared to neoplastic nodules that had a
      more irregular surface, with 93% having mineralized foci and rarely any
      hypoattenuating pockets. Non-neoplastic nodules were significantly more perfused
      than neoplastic nodules with the difference being up to 23 Hounsfield units. The
      difference was most marked in the early and late arterial phases (P = 0.0005 and
      0.00005, respectively). Ratios of the normal esophagus adjacent to the neoplastic
      and non-neoplastic nodules did not differ significantly from each other.
      Perfusion findings demonstrated relative hypoperfusion of the esophageal
      sarcomas. Findings from the current study indicated that CT characteristics of
      relative postcontrast hypoperfusion, combined with nodule irregularity and
      mineralization warrant a high level of concern for neoplastic transformation in
      canine spirocercosis-induced esophageal nodules. 

PMID- 25393218
TI  - Aspherical-atom modeling of coordination compounds by single-crystal X-ray
      diffraction allows the correct metal atom to be identified.
AB  - Single-crystal X-ray diffraction (XRD) is often considered the gold standard in
      analytical chemistry, as it allows element identification as well as
      determination of atom connectivity and the solid-state structure of completely
      unknown samples. Element assignment is based on the number of electrons of an
      atom, so that a distinction of neighboring heavier elements in the periodic table
      by XRD is often difficult. A computationally efficient procedure for aspherical
      atom least-squares refinement of conventional diffraction data of organometallic
      compounds is proposed. The iterative procedure is conceptually similar to
      Hirshfeld-atom refinement (Acta Crystallogr. Sect. A- 2008, 64, 383-393; IUCrJ.
      2014, 1,61-79), but it relies on tabulated invariom scattering factors (Acta
      Crystallogr. Sect. B- 2013, 69, 91-104) and the Hansen/Coppens multipole model;
      disordered structures can be handled as well. Five linear-coordinate 3d metal
      complexes, for which the wrong element is found if standard independent-atom
      model scattering factors are relied upon, are studied, and it is shown that only
      aspherical-atom scattering factors allow a reliable assignment. The influence of
      anomalous dispersion in identifying the correct element is investigated and
      discussed. 

PMID- 25393219
TI  - Nanog requires BRD4 to maintain murine embryonic stem cell pluripotency and is
      suppressed by bromodomain inhibitor JQ1 together with Lefty1.
AB  - Embryonic stem cells (ESCs) are maintained in an undifferentiated state through
      expression of the core transcriptional factors Nanog, Oct4, and Sox2. However,
      the epigenetic regulation of pluripotency is poorly understood. Differentiation
      of ESCs is accompanied by a global reduction of panacetylation of histones H3 and
      H4 suggesting that histone acetylation plays an important role in maintenance of
      ESC pluripotency. Acetylated lysine residues on histones are read by members of
      the bromodomain family that includes BET (bromodomain and extraterminal domain)
      proteins for which highly potent and selective inhibitors have been developed. In
      this study we demonstrate that the pan-BET bromodomain inhibitor JQ1 induces
      rapid spontaneous differentiation of murine ESCs by inducing marked
      transcriptional downregulation of Nanog as well as the stemness markers Lefty1
      and Lefty2, but not Myc, often used as a marker of BET inhibitor activity in
      cancer. We show that the effects of JQ1 are recapitulated by knockdown of the BET
      family member BRD4 implicating this protein in Nanog regulation. These data are
      also supported by chromatin immunoprecipitation experiments which confirm BRD4
      binding at the Nanog promoter that is known to require acetylation by the histone
      acetyltransferase MOF for transcriptional activity. In further support of our
      findings, we show that JQ1 antagonizes the stem cell-promoting effects of the
      histone deacetylase inhibitors sodium butyrate and valproic acid. Our data
      suggest that BRD4 is critical for the maintenance of ESC pluripotency and that
      this occurs primarily through the maintenance of Nanog expression. 

PMID- 25393220
TI  - Tobacco use among middle and high school students--United States, 2013.
AB  - Tobacco use is the leading preventable cause of disease and death in the United
      States, and nearly all tobacco use begins during youth and young adulthood. Among
      U.S. youths, cigarette smoking has declined in recent years; however, the use of
      some other tobacco products has increased, and nearly half of tobacco users use
      two or more tobacco products. CDC analyzed data from the 2013 National Youth
      Tobacco Survey to determine the prevalence of ever (at least once) and current
      (at least 1 day in the past 30 days) use of one or more of 10 tobacco products
      (cigarettes, cigars, hookahs, smokeless tobacco, electronic cigarettes [e
      cigarettes], pipes, snus, bidis, kreteks, and dissolvable tobacco) among U.S.
      middle school (grades 6-8) and high school (grades 9-12) students. In 2013, 22.9%
      of high school students reported current use of any tobacco product, and 12.6%
      reported current use of two or more tobacco products; current use of combustible
      products (i.e., cigarettes, cigars, pipes, bidis, kreteks, and/or hookahs) was
      substantially greater (20.7%) than use of other types of tobacco. Also, 46.0% of
      high school students reported having ever tried a tobacco product, and 31.4%
      reported ever trying two or more tobacco products. Among middle school students,
      3.1% reported current use of cigars, and 2.9% reported current use of cigarettes,
      with non-Hispanic black students more than twice as likely to report current use
      of cigars than cigarettes. Monitoring the prevalence of the use of all available
      tobacco products, including new and emerging products, is critical to support
      effective population-based interventions to prevent and reduce tobacco use among
      youths as part of comprehensive tobacco prevention and control programs. 

PMID- 25393221
TI  - Estimated burden of keratitis--United States, 2010.
AB  - Keratitis, inflammation of the cornea, can result in partial or total loss of
      vision and can result from infectious agents (e.g., microbes including bacteria,
      fungi, amebae, and viruses) or from noninfectious causes (e.g., eye trauma,
      chemical exposure, and ultraviolet exposure). Contact lens wear is the major risk
      factor for microbial keratitis; outbreaks of Fusarium and Acanthamoeba keratitis
      have been associated with contact lens multipurpose solution use, and poor
      contact lens hygiene is a major risk factor for a spectrum of eye complications,
      including microbial keratitis and other contact lens-related inflammation.
      However, the overall burden and the epidemiology of keratitis in the United
      States have not been well described. To estimate the incidence and cost of
      keratitis, national ambulatory-care and emergency department databases were
      analyzed. The results of this analysis showed that an estimated 930,000 doctor's
      office and outpatient clinic visits and 58,000 emergency department visits for
      keratitis or contact lens disorders occur annually; 76.5% of keratitis visits
      result in antimicrobial prescriptions. Episodes of keratitis and contact lens
      disorders cost an estimated $175 million in direct health care expenditures,
      including $58 million for Medicare patients and $12 million for Medicaid patients
      each year. Office and outpatient clinic visits occupied over 250,000 hours of
      clinician time annually. Developing effective prevention messages that are
      disseminated to contact lens users and investigation of additional preventive
      efforts are important measures to reduce the national incidence of microbial
      keratitis. 

PMID- 25393222
TI  - Possible eradication of wild poliovirus type 3--worldwide, 2012.
AB  - In 1988, the World Health Assembly resolved to eradicate polio worldwide. Since
      then, four of the six World Health Organization (WHO) regions have been certified
      as polio-free: the Americas in 1994, the Western Pacific Region in 2000, the
      European Region in 2002, and the South-East Asia Region in 2014. Currently,
      nearly 80% of the world's population lives in areas certified as polio-free.
      Certification may be considered when >=3 years have passed since the last
      isolation of wild poliovirus (WPV) in the presence of sensitive, certification
      standard surveillance. Although regional eradication has been validated in the
      European Region and the Western Pacific Region, outbreaks resulting from WPV type
      1 (WPV1) imported from known endemic areas were detected and controlled in these
      regions in 2010 and 2011, respectively. The last reported case associated with
      WPV type 2 (WPV2) was in India in 1999, marking global interruption of WPV2
      transmission. The completion of polio eradication was declared a programmatic
      emergency for public health in 2012, and the international spread of WPV1 was
      declared a public health emergency of international concern in May 2014. The
      efforts needed to interrupt all indigenous WPV1 transmission are now being
      focused on the remaining endemic countries: Nigeria, Afghanistan, and Pakistan.
      WPV type 3 (WPV3) has not been detected in circulation since November 11, 2012.
      This report summarizes the evidence of possible global interruption of
      transmission of WPV3, based on surveillance for acute flaccid paralysis (AFP) and
      environmental surveillance. 

PMID- 25393223
TI  - Progress toward regional measles elimination--worldwide, 2000-2013.
AB  - In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan with
      the objective to eliminate measles in four World Health Organization (WHO)
      regions by 2015. Member states of all six WHO regions have adopted measles
      elimination goals. In 2010, the World Health Assembly established three
      milestones for 2015: 1) increase routine coverage with the first dose of measles
      containing vaccine (MCV1) for children aged 1 year to >=90% nationally and >=80%
      in every district; 2) reduce global annual measles incidence to <5 cases per
      million; and 3) reduce global measles mortality by 95% from the 2000 estimate.
      This report updates the 2000-2012 report and describes progress toward global
      control and regional measles elimination during 2000-2013. During this period,
      annual reported measles incidence declined 72% worldwide, from 146 to 40 per
      million population, and annual estimated measles deaths declined 75%, from
      544,200 to 145,700. Four of six WHO regions have established regional
      verification commissions (RVCs); in the European (EUR) and Western Pacific
      regions (WPR), 19 member states successfully documented the absence of endemic
      measles. Resuming progress toward 2015 milestones and elimination goals will
      require countries and their partners to raise the visibility of measles
      elimination, address barriers to measles vaccination, and make substantial and
      sustained additional investments in strengthening health systems. 

PMID- 25393224
TI  - Combined hepatoid and serous carcinoma of the uterine corpus: an undescribed
      phenomenon.

PMID- 25393226
TI  - Making palliative care matter.

PMID- 25393225
TI  - Associations between use of pharmacological aids in a smoking cessation attempt
      and subsequent quitting activity: a population study.
AB  - BACKGROUND AND AIMS: Modelling the population impact and cost-effectiveness of
      smoking cessation aids is limited by lack of knowledge about how the use of aids
      changes across quit attempts. Here we test whether the quit method used in a
      previous attempt influences (i) future decisions to quit and/or (ii) treatment/s
      used during subsequent attempts. DESIGN AND SETTING: Data came from the Smoking
      Toolkit Study, a United Kingdom national household survey. PARTICIPANTS AND
      MEASURES: Smokers (n = 5489) who completed a baseline and 6-month follow-up
      questionnaire. Respondents were asked what treatment/s, grouped as: prescription
      medication/s [bupropion, varenicline or nicotine replacement therapy (NRT)], over
      the-counter NRT or unaided that they had used in their most recent quit attempt
      (at baseline), and any use of treatment/s for a quit attempt in the last 3 months
      at follow-up. RESULTS: Smokers who had tried to quit at baseline were more likely
      to report having tried to quit again prior to follow-up [all odds ratios >= 2.19
      relative to no attempt at baseline, P < 0.001]. Smokers who tried to quit using
      pharmacological aids were more likely to try to quit again at follow-up (all ORs
      >= 2.19 relative to no attempt at baseline, P < 0.001). Smokers tended to re-try
      aids used in baseline attempts in future attempts (all ORs >= 1.48 relative to no
      attempt at baseline, P < 0.01). CONCLUSIONS: Smokers who have tried to quit in
      the past year are more likely to try to quit again within 6 months regardless of
      whether they used a pharmacological aid, and they are more likely to re-try aids
      they had used previously.

PMID- 25393227
TI  - Direct cytosolic delivery of siRNA using nanoparticle-stabilized nanocapsules.
AB  - The use of nanoparticle-stabilized nanocapsules (NPSCs) for the direct cytosolic
      delivery of siRNA is reported. In this approach, siRNA is complexed with cationic
      arginine-functionalized gold nanoparticles by electrostatic interactions, with
      the resulting ensemble self-assembled onto the surface of fatty acid nanodroplets
      to form a NPSC/siRNA nanocomplex. The complex rapidly delivers siRNA into the
      cytosol through membrane fusion, a mechanism supported by cellular uptake
      studies. Using destabilized green fluorescent protein (deGFP) as a target, 90%
      knockdown was observed in HEK293 cells. Moreover, the delivery of siRNA targeting
      polo-like kinase 1 (siPLK1) efficiently silenced PLK1 expression in cancer cells
      with concomitant cytotoxicity.

PMID- 25393230
TI  - Nonlocal thermal transport across embedded few-layer graphene sheets.
AB  - Thermal transport across the interfaces between few-layer graphene sheets and
      soft materials exhibits intriguing anomalies when interpreted using the classical
      Kapitza model, e.g. the conductance of the same interface differs greatly for
      different modes of interfacial thermal transport. Using atomistic simulations, we
      show that such thermal transport follows a nonlocal flux-temperature drop
      constitutive law and is characterized jointly by a quasi-local conductance and a
      nonlocal conductance instead of the classical Kapitza conductance. The nonlocal
      model enables rationalization of many anomalies of the thermal transport across
      embedded few-layer graphene sheets and should be used in studies of interfacial
      thermal transport involving few-layer graphene sheets or other ultra-thin layered
      materials. 

PMID- 25393229
TI  - Gaseous emissions from management of solid waste: a systematic review.
AB  - The establishment of sustainable soil waste management practices implies
      minimizing their environmental losses associated with climate change (greenhouse
      gases: GHGs) and ecosystems acidification (ammonia: NH3 ). Although a number of
      management strategies for solid waste management have been investigated to
      quantify nitrogen (N) and carbon (C) losses in relation to varied environmental
      and operational conditions, their overall effect is still uncertain. In this
      context, we have analyzed the current scientific information through a systematic
      review. We quantified the response of GHG emissions, NH3 emissions, and total N
      losses to different solid waste management strategies (conventional solid
      storage, turned composting, forced aerated composting, covering, compaction,
      addition/substitution of bulking agents and the use of additives). Our study is
      based on a meta-analysis of 50 research articles involving 304 observations. Our
      results indicated that improving the structure of the pile (waste or manure heap)
      via addition or substitution of certain bulking agents significantly reduced
      nitrous oxide (N2 O) and methane (CH4 ) emissions by 53% and 71%, respectively.
      Turned composting systems, unlike forced aerated composted systems, showed
      potential for reducing GHGs (N2 O: 50% and CH4 : 71%). Bulking agents and both
      composting systems involved a certain degree of pollution swapping as they
      significantly promoted NH3 emissions by 35%, 54%, and 121% for bulking agents,
      turned and forced aerated composting, respectively. Strategies based on the
      restriction of O2 supply, such as covering or compaction, did not show
      significant effects on reducing GHGs but substantially decreased NH3 emissions by
      61% and 54% for covering and compaction, respectively. The use of specific
      additives significantly reduced NH3 losses by 69%. Our meta-analysis suggested
      that there is enough evidence to refine future Intergovernmental Panel on Climate
      Change (IPCC) methodologies from solid waste, especially for solid waste
      composting practices. More holistic and integrated approaches are therefore
      required to develop more sustainable solid waste management systems. 

PMID- 25393231
TI  - A chemoenzymatic and fully stereocontrolled total synthesis of the antibacterial
      natural product (-)-platencin.
AB  - The natural product (-)-platencin is a potent antibacterial agent that exerts its
      effects through a novel mode of action. As such, it is an important lead in the
      development of next-generation antibacterials that are urgently needed because of
      the rapidly developing resistance to current therapies. The work reported here
      concerns the development of a convergent and chemoenzymatic total synthesis of (
      )-platencin by methods that should provide access to a range of biologically
      relevant analogues. The key step involves a thermally promoted and facially
      selective intramolecular Diels-Alder (IMDA) cycloaddition reaction to give an
      adduct that embodies the tricarbocyclic core of (-)-platencin. This adduct was
      elaborated over thirteen steps to the natural product. The substrate for the IMDA
      reaction was prepared by Stille cross-coupling of a Z-configured alkenylstannane
      with an iodinated diene obtained in an enantiomerically pure form through the
      whole-cell biotransformation of iodobenzene. 

PMID- 25393233
TI  - Reliability of the Dynamic Strength Index in college athletes.
AB  - PURPOSE: To determine the reliability of the Dynamic Strength Index (DSI) in
      college athletes. METHOD: Nineteen male college athletes performed the squat jump
      (SJ) and isometric midthigh pull (IMTP) to determine peak force, on 2 separate
      days. Reliability was assessed by intraclass correlation coefficient (ICC),
      typical error (TE), percentage change in the mean, smallest worthwhile change
      (SWC), and coefficient of variation (%CV). RESULTS: Peak force for the SJ was
      2137+/-499 N and 2781+/-435 N for the IMTP, resulting in a mean DSI of 0.78+/
      0.19. Peak forces in the SJ (ICC=.99, TE=57.22 N, change in mean=0.2%, SWC=4.7%,
      CV=2.6%) and IMTP (ICC=.95, TE=104.22 N, change in mean=0.5%, SWC=3.1%, CV=3.8%)
      were considered highly reliable between sessions. However, IMTP peak force was
      the only variable with an overall TE<SWC. The DSI was also highly reliable
      (ICC=.97, TE=0.03, change in mean=-0.3%, SWC=5.1%, CV=4.6%) between sessions.
      CONCLUSION: This study demonstrates that peak force in the SJ and IMTP are
      reliable, resulting in a reliable assessment of dynamic-force-production
      capabilities via the DSI. The DSI may be used to guide individualized training
      interventions and monitor specific adaptations to training. Changes in SJ peak
      force, IMTP peak force, and DSI were >4.67%, 3.13%, and 5.13%, respectively,
      identifying meaningful changes in response to training or competition.

PMID- 25393234
TI  - Prioritizing tiger conservation through landscape genetics and habitat linkages.
AB  - Even with global support for tiger (Panthera tigris) conservation their survival
      is threatened by poaching, habitat loss and isolation. Currently about 3,000 wild
      tigers persist in small fragmented populations within seven percent of their
      historic range. Identifying and securing habitat linkages that connect source
      populations for maintaining landscape-level gene flow is an important long-term
      conservation strategy for endangered carnivores. However, habitat corridors that
      link regional tiger populations are often lost to development projects due to
      lack of objective evidence on their importance. Here, we use individual based
      genetic analysis in combination with landscape permeability models to identify
      and prioritize movement corridors across seven tiger populations within the
      Central Indian Landscape. By using a panel of 11 microsatellites we identified
      169 individual tigers from 587 scat and 17 tissue samples. We detected four
      genetic clusters within Central India with limited gene flow among three of them.
      Bayesian and likelihood analyses identified 17 tigers as having recent immigrant
      ancestry. Spatially explicit tiger occupancy obtained from extensive landscape
      scale surveys across 76,913 km(2) of forest habitat was found to be only 21,290
      km(2). After accounting for detection bias, the covariates that best explained
      tiger occupancy were large, remote, dense forest patches; large ungulate
      abundance, and low human footprint. We used tiger occupancy probability to
      parameterize habitat permeability for modeling habitat linkages using least-cost
      and circuit theory pathway analyses. Pairwise genetic differences (FST) between
      populations were better explained by modeled linkage costs (r>0.5, p<0.05)
      compared to Euclidean distances, which was in consonance with observed habitat
      fragmentation. The results of our study highlight that many corridors may still
      be functional as there is evidence of contemporary migration. Conservation
      efforts should provide legal status to corridors, use smart green infrastructure
      to mitigate development impacts, and restore habitats where connectivity has been
      lost.

PMID- 25393235
TI  - Identification of novel genetic risk loci in Maltese dogs with necrotizing
      meningoencephalitis and evidence of a shared genetic risk across toy dog breeds.
AB  - Necrotizing meningoencephalitis (NME) affects toy and small breed dogs causing
      progressive, often fatal, inflammation and necrosis in the brain. Genetic risk
      loci for NME previously were identified in pug dogs, particularly associated with
      the dog leukocyte antigen (DLA) class II complex on chromosome 12, but have not
      been investigated in other susceptible breeds. We sought to evaluate Maltese and
      Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk
      factors for NME development. Genome-wide association testing of single nucleotide
      polymorphisms (SNPs) in Maltese dogs with NME identified 2 regions of genome-wide
      significance on chromosomes 4 (chr4:74522353T>A, p = 8.1*10-7) and 15
      (chr15:53338796A>G, p = 1.5*10-7). Haplotype analysis and fine-mapping suggests
      that ILR7 and FBXW7, respectively, both important for regulation of immune system
      function, could be the underlying associated genes. Further evaluation of these
      regions and the previously identified DLA II locus across all three breeds,
      revealed an enrichment of nominal significant SNPs associated with chromosome 15
      in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed
      effect sizes the same direction in all three breeds for both the chromosome 15
      and DLA II loci (p = 8.6*10-11 and p = 2.5*10-7, respectively). This suggests a
      shared genetic background exists between all breeds and confers susceptibility to
      NME, but effect sizes might be different among breeds. In conclusion, we
      identified the first genetic risk factors for NME development in the Maltese,
      chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk
      between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R
      both have been implicated in human inflammatory diseases of the central nervous
      system such as multiple sclerosis, suggesting that similar pharmacotherapeutic
      targets across species should be investigated. 

PMID- 25393236
TI  - "Those comments last forever": parents and grandparents of preschoolers recount
      how they became aware of their own body weights as children.
AB  - BACKGROUND: Parents' and grandparents' willingness to talk about children's body
      weights may be influenced by their own childhood experiences of body weight
      awareness and 'weight talk' in the family; however, little is known about how
      adults describe their recollected weight-related childhood experiences. AIMS:
      This paper examines how parents and grandparents of preschoolers describe the
      emergence of their own body weight awareness in childhood or adolescence. The
      analysis highlights the sources that participants identify as having instigated
      their body weight awareness, the feelings and experiences participants associate
      with the experience of becoming aware of their body weights, and their framings
      of potential links between childhood experiences and attitudes and practices in
      adulthood. METHODS: 49 participants (22 parents, 27 grandparents, 70% women, 60%
      with overweight/obesity) from sixteen low-income families of children aged 3-5
      years (50% girls, 56% with overweight/obesity) in the Pacific Northwest were
      interviewed. The interviews were videotaped, transcribed, and analyzed
      qualitatively. RESULTS: Twenty-five participants (51%) said they became aware of
      their body weights in childhood or adolescence. Fourteen participants said their
      body weight awareness emerged through comments made by others, with the majority
      citing parents or peers. No participant described the emergence of body weight
      awareness in positive terms. Four participants directly linked their own negative
      experiences to the decision not to discuss body weight with their preschoolers.
      All four cited critical comments from their parents as instigating their own body
      weight awareness in childhood. CONCLUSIONS: In most cases, participants
      associated their emergent awareness of body weight with overtly negative feelings
      or consequences; some participants said these negative experiences continued to
      affect them as adults. Since family-based childhood obesity interventions involve
      open discussion of children's body sizes, the results suggest that clinicians
      should reframe the discussion to deconstruct obesity stigma and emphasize
      inclusive, affirmative, and health-focused messages.

PMID- 25393238
TI  - Facile and label-free detection of lung cancer biomarker in urine by magnetically
      assisted surface-enhanced Raman scattering.
AB  - Adenosine plays a crucial role in the regulation of physiological activity in
      various tissues and organs. As adenosine is a possible biomarker for cancer, the
      determination of its level presents a demanding task for deeply monitoring
      progress of diseases. Through the synthesis of Fe3O4/Au/Ag nanocomposites weaved
      and stabilized by phytic acid and its salt, we develop a magnetically assisted
      surface-enhanced Raman scattering (SERS) protocol to determine trace level
      adenosine in urine samples from both lung cancer patients and health human. The
      magnetic properties of the nanocomposites enable to realize the simple separation
      of targeted molecules from a complex matrix and the Au/Ag nanoparticles moieties
      act as the SERS platform. This label-free Fe3O4/Au/Ag-nanocomposites-based SERS
      protocol shows a good stability, reproducibility, time efficiency (less than 20
      min for one sample test), and huge sensitivity down to 1 * 10(-10) M. The
      protocol also has high selectivity because SERS signal of adenosine provides the
      molecular fingerprint information as well as an azo coupling pretreatment is
      performed to remove the interference of urea. Furthermore, a SERS array is
      designed for on-site screening adenosine in urine samples in a massive way using
      a portable Raman. Such a magnetically assisted SERS method as a powerful
      alternative can be expected as a smart and promising tool for effective
      assessment of healthcare. 

PMID- 25393237
TI  - Viral load, integration and methylation of E2BS3 and 4 in human papilloma virus
      (HPV) 16-positive vaginal and vulvar carcinomas.
AB  - OBJECTIVE: To investigate if viral load, integration and methylation of E2BS3 and
      4 represent different ways of tumor transformation in vaginal and vulvar
      carcinoma and to elucidate its clinical impact. METHODS: Fifty-seven samples,
      positive for HPV16, were selected for the study. Detection of viral load was made
      with realtime-PCR using copy numbers of E6 and integration was calculated from
      comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using
      bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing. RESULTS:
      Vaginal tumors were found to have a higher viral load (p = 0.024) compared to
      vulvar tumors but a high copy number (> median value, 15,000) as well as high
      methylation (>50%) was significantly (p = 0.010 and p = 0.045) associated with a
      worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal
      carcinoma. Four groups could be defined for the complete series using a Cluster
      Two step analysis; (1) tumors holding episomal viral DNA, viral load below
      150,000 copies not highly methylated (n = 25, 46.3%); (2) tumors harboring
      episomal viral DNA and being highly methylated (>50%; n = 6, 11.1%); (3) tumors
      with viral DNA fully integrated (n = 11, 20.4%), and (4) tumors harboring
      episomal viral DNA and being medium- or unmethylated (<50%) and having a high
      viral load (> total mean value 150,000; n = 12, 22.2%). The completely integrated
      tumors were found to be distinct group, whilst some overlap between the groups
      with high methylation and high viral load was observed. CONCLUSION: HPV16-
      related integration, methylation in E2BS3 and 4 and viral load may represent
      different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16-
      related parameters were found to be of clinical importance in the vulvar series
      only.

PMID- 25393239
TI  - Insights into RNA transcriptome profiling of cardiac tissue in obesity and
      hypertension conditions.
AB  - Several epidemiologic studies suggest that obesity and hypertension are
      associated with cardiac transcriptome modifications that could be further
      associated with inflammatory processes and cardiac hypertrophy. In this field,
      transcriptome studies have demonstrated their importance to elucidate physiologic
      mechanisms, pathways or genes involved in many biologic processes. Over the past
      decade, RNA microarray and RNA-seq analysis has become an essential component to
      examine metabolic pathways in terms of mRNA expression in cardiology. In this
      review, cardiac muscle gene expression in response to effects of obesity and
      hypertension will be focused, providing a broad view on cardiac transcriptome and
      physiologic and biochemical mechanisms involved in gene expression changes
      produced by these events, emphasizing the use of new technologies for gene
      expression analyses.

PMID- 25393240
TI  - The great roundleaf bat (Hipposideros armiger) as a good model for cold-induced
      browning of intra-abdominal white adipose tissue.
AB  - BACKGROUND: Inducing beige fat from white adipose tissue (WAT) is considered to
      be a shortcut to weight loss and increasingly becoming a key area in research
      into treatments for obesity and related diseases. However, currently, animal
      models of beige fat are restricted to rodents, where subcutaneous adipose tissue
      (sWAT, benign WAT) is more liable to develop into the beige fat under specific
      activators than the intra-abdominal adipose tissue (aWAT, malignant WAT) that is
      the major source of obesity related diseases in humans. METHODS: Here we induced
      beige fat by cold exposure in two species of bats, the great roundleaf bat
      (Hipposideros armiger) and the rickett's big-footed bat (Myotis ricketti), and
      compared the molecular and morphological changes with those seen in the mouse.
      Expression of thermogenic genes (Ucp1 and Pgc1a) was measured by RT-qPCR and
      adipocyte morphology examined by HE staining at three adipose locations, sWAT,
      aWAT and iBAT (interscapular brown adipose tissue). RESULTS: Expression of Ucp1
      and Pgc1a was significantly upregulated, by 729 and 23 fold, respectively, in
      aWAT of the great roundleaf bat after exposure to 10 degrees C for 7 days.
      Adipocyte diameters of WATs became significantly reduced and the white adipocytes
      became brown-like in morphology. In mice, similar changes were found in the sWAT,
      but much lower amounts of changes in aWAT were seen. Interestingly, the rickett's
      big-footed bat did not show such a tendency in beige fat. CONCLUSIONS: The great
      roundleaf bat is potentially a good animal model for human aWAT browning
      research. Combined with rodent models, this model should be helpful for finding
      therapies for reducing harmful aWAT in humans.

PMID- 25393241
TI  - Attitudes about tuberculosis prevention in the elimination phase: a survey among
      physicians in Germany.
AB  - BACKGROUND: Targeted and stringent measures of tuberculosis prevention are
      necessary to achieve the goal of tuberculosis elimination in countries of low
      tuberculosis incidence. METHODS: We ascertained the knowledge about tuberculosis
      risk factors and stringency of tuberculosis prevention measures by a standardized
      questionnaire among physicians in Germany involved in the care of individuals
      from classical risk groups for tuberculosis. RESULTS: 510 physicians responded to
      the online survey. Among 16 risk factors immunosuppressive therapy, HIV-infection
      and treatment with TNF-antagonist were thought to be the most important risk
      factors for the development of tuberculosis in Germany. Exposure to a patient
      with tuberculosis ranked on the 10th position. In the event of a positive
      tuberculin-skin-test or interferon-gamma release assay only 50%, 40%, 36% and 25%
      of physicians found that preventive chemotherapy was indicated for individuals
      undergoing tumor necrosis factor-antagonist therapy, close contacts of
      tuberculosis patients, HIV-infected individuals and migrants, respectively.
      CONCLUSIONS: A remarkably low proportion of individuals with latent infection
      with Mycobacterium tuberculosis belonging to classical risk groups for
      tuberculosis are considered candidates for preventive chemotherapy in Germany.
      Better knowledge about the risk for tuberculosis in different groups and more
      stringent and targeted preventive interventions will probably be necessary to
      achieve tuberculosis elimination in Germany.

PMID- 25393243
TI  - Selection of reference genes for quantitative real-time PCR normalization in
      Panax ginseng at different stages of growth and in different organs.
AB  - Quantitative real-time reverse transcription PCR (qRT-PCR) has become a widely
      used method for gene expression analysis; however, its data interpretation
      largely depends on the stability of reference genes. The transcriptomics of Panax
      ginseng, one of the most popular and traditional ingredients used in Chinese
      medicines, is increasingly being studied. Furthermore, it is vital to establish a
      series of reliable reference genes when qRT-PCR is used to assess the gene
      expression profile of ginseng. In this study, we screened out candidate reference
      genes for ginseng using gene expression data generated by a high-throughput
      sequencing platform. Based on the statistical tests, 20 reference genes (10
      traditional housekeeping genes and 10 novel genes) were selected. These genes
      were tested for the normalization of expression levels in five growth stages and
      three distinct plant organs of ginseng by qPCR. These genes were subsequently
      ranked and compared according to the stability of their expressions using geNorm,
      NormFinder, and BestKeeper computational programs. Although the best reference
      genes were found to vary across different samples, CYP and EF-1alpha were the
      most stable genes amongst all samples. GAPDH/30S RPS20, CYP/60S RPL13 and CYP/QCR
      were the optimum pair of reference genes in the roots, stems, and leaves. CYP/60S
      RPL13, CYP/eIF-5A, aTUB/V-ATP, eIF-5A/SAR1, and aTUB/pol IIa were the most stably
      expressed combinations in each of the five developmental stages. Our study serves
      as a foundation for developing an accurate method of qRT-PCR and will benefit
      future studies on gene expression profiles of Panax Ginseng. 

PMID- 25393245
TI  - Biophysical impacts of climate-smart agriculture in the Midwest United States.
AB  - The potential impacts of climate change in the Midwest United States present
      unprecedented challenges to regional agriculture. In response to these
      challenges, a variety of climate-smart agricultural methodologies have been
      proposed to retain or improve crop yields, reduce agricultural greenhouse gas
      emissions, retain soil quality and increase climate resilience of agricultural
      systems. One component that is commonly neglected when assessing the
      environmental impacts of climate-smart agriculture is the biophysical impacts,
      where changes in ecosystem fluxes and storage of moisture and energy lead to
      perturbations in local climate and water availability. Using a combination of
      observational data and an agroecosystem model, a series of climate-smart
      agricultural scenarios were assessed to determine the biophysical impacts these
      techniques have in the Midwest United States. The first scenario extended the
      growing season for existing crops using future temperature and CO2
      concentrations. The second scenario examined the biophysical impacts of no-till
      agriculture and the impacts of annually retaining crop debris. Finally, the third
      scenario evaluated the potential impacts that the adoption of perennial cultivars
      had on biophysical quantities. Each of these scenarios was found to have
      significant biophysical impacts. However, the timing and magnitude of the
      biophysical impacts differed between scenarios. 

PMID- 25393244
TI  - Clinical features and patient management of Lujo hemorrhagic fever.
AB  - BACKGROUND: In 2008 a nosocomial outbreak of five cases of viral hemorrhagic
      fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South
      Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus,
      to be recognized in Africa and the first in over 40 years. Because of the remote,
      resource-poor, and often politically unstable regions where Lassa fever and other
      viral hemorrhagic fevers typically occur, there have been few opportunities to
      undertake in-depth study of their clinical manifestations, transmission dynamics,
      pathogenesis, or response to treatment options typically available in
      industrialized countries. METHODS AND FINDINGS: We describe the clinical features
      of five cases of Lujo hemorrhagic fever and summarize their clinical management,
      as well as providing additional epidemiologic detail regarding the 2008 outbreak.
      Illness typically began with the abrupt onset of fever, malaise, headache, and
      myalgias followed successively by sore throat, chest pain, gastrointestinal
      symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial
      swelling over the first week of illness. No major hemorrhage was noted.
      Neurological signs were sometimes seen in the late stages. Shock and multi-organ
      system failure, often with evidence of disseminated intravascular coagulopathy,
      ensued in the second week, with death in four of the five cases. Distinctive
      treatment components of the one surviving patient included rapid commencement of
      the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors
      (statins), N-acetylcysteine, and recombinant factor VIIa. CONCLUSIONS: Lujo virus
      causes a clinical syndrome remarkably similar to Lassa fever. Considering the
      high case-fatality and significant logistical impediments to controlled treatment
      efficacy trials for viral hemorrhagic fever, it is both logical and ethical to
      explore the use of the various compounds used in the treatment of the surviving
      case reported here in future outbreaks. Clinical observations should be
      systematically recorded to facilitate objective evaluation of treatment efficacy.
      Due to the risk of secondary transmission, viral hemorrhagic fever precautions
      should be implemented for all cases of Lujo virus infection, with specialized
      precautions to protect against aerosols when performing enhanced-risk procedures
      such as endotracheal intubation.

PMID- 25393246
TI  - Optimising pre-analytical factors affecting quality of prostate biopsies: the
      case for site specific labelling and single core submission.

PMID- 25393247
TI  - In situ hybridisation for Epstein-Barr virus as a differential diagnostic tool
      for T- and natural killer/T-cell lymphomas in non-immunocompromised patients.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus infecting over 90% of
      humans and the infection persists for life. Although most people are
      asymptomatic, EBV infection may cause a continuous range of symptoms from
      transient to severe and protracted diseases depending on the immunological
      response of the individuals. EBV infects primarily B lymphocytes and rarely T and
      natural killer (NK) cells. It is implicated in around 1% of human tumours with
      the majority being haematological malignancies including Hodgkin lymphoma, B- and
      T-cell non-Hodgkin lymphomas, and immunodeficiency-associated lymphoproliferative
      disorders (LPDs). As it is a ubiquitous virus the confirmation of EBV-related
      LPDs depends on the demonstration of the viral DNA by in situ hybridisation for
      EBV-encoded mRNA (EBER). In current practice, CD3 and EBER positive cytotoxic
      extranodal lymphomas in non-immunocompromised patients are generally considered
      as extranodal NK/T-cell lymphoma and accordingly EBER should be performed for
      such tumours except for the few clinically typical entities such as mycosis
      fungoides. This review focuses on the application of EBER in the diagnosis of
      various types of T- and NK/T-cell lymphomas in non-immunocompromised patients and
      the diagnostic pitfalls, especially their distinction from infectious
      mononucleosis-related LPD of T- and NK-cell origins and the diagnostic dilemma
      between various T-cell lymphoma entities with or without EBV association,
      including nodal cytotoxic EBV positive peripheral T-cell lymphoma.

PMID- 25393249
TI  - Intimal sarcomas of the aorta and iliofemoral arteries: a clinicopathological
      study of 26 cases.
AB  - Aortic sarcomas are predominantly endoluminal tumours that are believed derived
      from the intima. Because of their rarity, relatively little is known about their
      pathological features. We report a series of 26 aortic and iliofemoral tumours
      with histopathological and clinical data.Of the 26 cases, there were 16 men (63.6
      +/- 13 years) and 10 women (58.6 +/- 18 years). Tumours occurred in the abdominal
      aorta (13), descending thoracic aorta (8), iliac or femoral arteries (4) and
      ascending aorta (1). Presenting tumour manifestations included claudication or
      peripheral vascular disease (6), pain (5), pulsatile aneurysm (2) abdominal
      aortic aneurysm (AAA; 2), occluded graft (2), renal artery stenosis (1), pain
      from bone metastasis (1), aortic rupture (1), fever (1), weight loss (1),
      vasculitis (1) impotence (1), incidental finding (1) and bowel ischaemia (1). The
      diagnosis was not suspected clinically in any case. The tumours were sampled by
      endarterectomy (9), aortic resection (8), repair of aneurysm (5), and in four the
      diagnosis was made at autopsy. Histologically and immunohistochemically, 13 were
      categorised as poorly differentiated angiosarcomas, seven as undifferentiated
      sarcomas, three as osteosarcomas, two as myxofibrosarcomas, and one as myxoid
      sarcoma, not otherwise specified. The undifferentiated sarcomas and angiosarcomas
      were histologically similar to one another and were characterised by tumour cells
      within and overlying thrombus. The angiosarcomas were defined by diffuse CD31
      expression with co-expression of pancytokeratin in 10 (77%). Undifferentiated
      sarcomas were composed of spindled and/or epithelioid cells and 71% expressed
      smooth muscle actin. Histological material from metastatic tumours was available
      in two osteosarcomas and two undifferentiated sarcomas, and showed
      undifferentiated pleomorphic sarcoma in all cases.In this series, half of aortic
      intimal sarcomas are histologically undifferentiated and express endothelial and
      epithelial markers (epithelioid angiosarcoma). The second largest group is
      undifferentiated sarcoma without immunohistochemical evidence of endothelial
      differentiation and frequent actin positivity. Rare types include
      myxofibrosarcoma and osteosarcoma.

PMID- 25393248
TI  - The Australian experience with the Bethesda classification system for thyroid
      fine needle aspiration biopsies.
AB  - Fine needle aspiration biopsy (FNAB) is the initial investigation of choice for
      thyroid nodules. The Bethesda system, which classifies thyroid FNABs into
      different categories each linked to a risk of malignancy, has been widely
      adopted. However, the risk of malignancy implied by each Bethesda category is
      likely to vary due to population characteristics and inconsistency in the
      application of diagnostic criteria.We present our experience of the Bethesda
      system in 2076 thyroid nodules from 1410 patients. Categories were as follows:
      266 (12.8%) were category 1 (B1) non-diagnostic, 1551 (74.7%) category 2 (B2)
      benign, 97 (4.7%) category 3 (B3) atypia of uncertain significance, 98 (4.7%)
      category 4 (B4) suspicious for follicular neoplasm, 16 (0.8%) category 5 (B5)
      suspicious for malignancy and 48 (2.3%) category 6 (B6) malignant.Surgery was
      performed on 425 nodules from 315 patients. Malignancy rates in the target
      nodules were B1 4.2%, B2 0.26%, B3 9.3%, B4 15.3%, B5 79% and B6 100%. Twelve
      patients with B3 nodules underwent repeat FNAB, with eight reclassified as B2,
      one as B3, one as B1 and two as B4. An incidental microcarcinoma separate to the
      target nodule was identified in 11.1%.As applied in our institution, and despite
      very sparing use of B3 and B5 categories, our audit has demonstrated risks of
      malignancy broadly in keeping with that predicted. Of note, the risk of
      malignancy in the clinically indeterminate categories of B1, B3 and B4 were all
      at the lower ranges of those predicted in the Bethesda atlas and mostly lower
      than those reported by other studies.

PMID- 25393250
TI  - Diffuse mesothelioma of the peritoneum: correlation between histological and
      clinical parameters and survival in 73 patients.
AB  - There are few studies addressing survival of diffuse peritoneal mesotheliomas
      (DPM).In this study, survival data were obtained retrospectively from 73 patients
      treated with intended cytoreductive surgery for DPM, with a mean follow-up of 42
      months. Mesotheliomas were classified as well differentiated papillary (WDPM, n =
      2), multicystic (MCM, n = 4), and epithelioid mesotheliomas were subclassified as
      tubulopapillary (TPM, n = 27), solid/deciduoid (S/DM, n = 34), and or biphasic
      mesothelioma (BPM, n = 6). Invasion was characterised as absent (grade 0), into
      stroma (grade 1), into fat (grade 2), and into adjacent structures (grade 3).
      Peritoneal cancer index (PCI) and completeness of cytoreduction (CCR) were
      assessed surgically.There were no deaths in the WDPM, MCM, and epithelioid DPM
      with <= grade 1 invasion. There was a stepwise decrease in overall survival from
      invasive TPM, S/DM, and BPM (p < 0.0001). By univariate analysis, advanced age (p
      = 0.01), incomplete CCR (p < 0.001), PCI (p = 0.004), mitotic count (p < 0.001),
      nuclear grade (p < 0.0001), stromal inflammation (p = 0.013), depth of invasion
      (p < 0.0001), necrosis (p = 0.002), and sarcomatoid growth (p < 0.0001) were
      associated with decreased overall survival. By multivariate analysis, only
      sarcomatoid growth (p = 0.0006), depth of invasion (p = 0.02), elevated CCR (CCR
      2-3) (p = 0.02), and presence of inflammatory stroma (p = 0.04) were significant
      variables associated with decreased overall survival.DPM form a spectrum of
      indolent to highly aggressive tumours. Solid epithelioid/deciduoid tumours have a
      prognosis intermediate between biphasic mesotheliomas and invasive TPM. The
      presence and degree of invasion, sarcomatoid features, and inflammatory stroma
      are poor prognostic indicators.

PMID- 25393251
TI  - Mycosis fungoides with large cell transformation: clinicopathological features
      and prognostic factors.
AB  - Large cell transformation of mycosis fungoides (MF-LCT) occurs in 20-50% of
      advanced MF, and is generally associated with poor prognosis, although some
      patients have indolent disease. We sought to identify clinicopathological
      prognostic factors in a large number of patients with MF-LCT.We identified
      patients with MF-LCT treated between 1991 and 2012 at a referral centre for
      cutaneous lymphoma. Clinical and pathological records, and histopathological
      slides were reviewed. Associations of clinicopathological variables with disease
      specific survival were analysed.In 51 patients with MF-LCT, factors significantly
      associated with shorter survival were: age >60 years (25 versus 61  months, p =
      0.01), stage III/IV (25 versus 44  months, p = 0.049), high serum lactate
      dehydrogenase (LDH; 24 versus 53  months, p = 0.007), absent papillary dermal
      involvement (8 versus 30  months, p = 0.008); follicular mucin at transformation
      (24 versus 42  months, p = 0.007); and the absence of fibrosis at transformation
      (21 versus 42  months, p = 0.03). Patients presenting with transformation at
      diagnosis had better survival than those who started with a small cell phenotype
      (p = 0.02). Age >60 years was independently associated with poorer survival (HR
      5.61, 95%CI 1.17-26.8, p = 0.03), and the presence of fibrosis at transformation
      was independently associated with improved survival (HR 0.30, 95%CI 0.09-0.97, p
      = 0.045).In patients with MF-LCT, clinical features (age, stage, serum LDH) are
      important in assessing prognosis. Additional clinical and pathological features
      identified in this study may also assist in prognostic stratification. Studies of
      larger cohorts should be performed to validate the prognostic significance of
      these features.

PMID- 25393252
TI  - High APRIL expression correlates with unfavourable survival of gastrointestinal
      stromal tumour.
AB  - A proliferation inducing ligand (APRIL) is a member of the tumour necrosis factor
      superfamily. High APRIL expression has been found to correlate with tumour
      development, suggesting that APRIL participates in oncogenesis. However, little
      is known about APRIL expression in gastrointestinal stromal tumours (GISTs) or
      the relationship between APRIL expression and the clinical characteristics of
      GIST. Therefore, we assessed the expression of APRIL immunohistochemically using
      a tissue microarray from 178 patients with GIST and evaluated the relationship
      between APRIL expression and patient prognosis. Strong APRIL expression was
      observed in 42.7% of GISTs, with APRIL expression significantly associated with
      tumour diameter, gross classification and tumour grade (p < 0.05 each). Kaplan
      Meier analysis suggested that low APRIL expression and tumour size <5 cm were
      associated with longer overall survival. These findings indicate that APRIL
      expression is correlated with malignant GIST phenotypes and it may serve as an
      unfavourable prognostic marker in patients with GIST.

PMID- 25393253
TI  - Expression of multidrug resistance 1 gene in association with CXCL12 in chronic
      myelogenous leukaemia.
AB  - Even though the BCR-ABL tyrosine kinase inhibitor imatinib significantly improves
      the prognosis of chronic myelogenous leukaemia (CML) patients, drug resistance is
      a major obstacle to better management. We examined the interaction of recently
      defined bone marrow microenvironment factors CXCL12 and ATP-binding cassette
      (ABC) transporters in the bone marrow of CML patients in the chronic phase and
      blast crisis.Expression levels of mRNA extracted from frozen specimens of CML
      patients were measured by real-time polymerase chain reaction. The expression of
      the ABC transporters MDR1, ABCC1, ABCG2, and CXCL12 was significantly higher in
      the bone marrow samples of CML blast crisis than in those of CML chronic phase.
      Immunohistochemical staining for CXCL12 revealed that the proportion of CXCL12
      positive reticular cell areas correlated well with the mRNA levels of CXCL12 in
      CML bone marrow. Finally, co-culture experiments of K562 CML cells with CXCL12
      expressing mesenchymal cells (OP9 cells or human CXCL12 transfected 3T3 cells)
      revealed enhanced mRNA levels for MDR1 in a CXCL12 rich environment.These results
      suggest that imatinib treatment restores the bone marrow microenvironment in CML
      with the presence of CXCL12 expressing reticular cells but in turn induces the
      overexpression of MDR1 in haematopoietic cells due to up-regulated expression of
      CXCL12.

PMID- 25393254
TI  - Hereditary protein C deficiency caused by compound heterozygous mutants in two
      independent Chinese families.
AB  - We report two compound heterozygous mutants that caused severe type I protein C
      (PC) deficiency in two independent Chinese families.PC antigen was determined by
      enzyme-linked immunosorbent assay (ELISA), and PC activity was measured by
      chromogenic assay. Genetic mutations were screened with polymerase chain reaction
      (PCR) followed by direct sequencing. PC mutants were transiently expressed in COS
      7 cells for the evaluation of PC secretory activity and function. The subcellular
      location was visualised by immunofluorescence assay. The structural analysis of
      mutation was performed as well.Compound heterozygous mutations of Arg178Trp and
      Asp255His with reduced PC activity and antigen levels were identified in Proband
      1, a 28-year-old male with deep vein thrombosis (DVT) and pulmonary embolism. The
      other mutations of Leu-34Pro and Thr295Ile with reduced PC activity and antigen
      levels were identified in Proband 2, a 19-year-old male with DVT. The PC
      activities with Arg178Trp, Asp255His, Leu-34Pro and Thr295Ile mutations decreased
      significantly. Immunofluorescence assay demonstrated that only trace amount of PC
      with novel Thr295Ile mutation was transported to the Golgi apparatus. Subsequent
      structural analysis indicated severe impairments of intracellular folding and
      secretion.The two rare compound heterozygous mutations could cause type I PC
      deficiency via impairment of secretory activity of PC.

PMID- 25393255
TI  - Clinical impact of reducing routine blood culture incubation time from 7 to 5
      days.
AB  - The aim of this study was to determine the clinical impact of reducing the blood
      culture incubation protocol from 7 to 5 days.A laboratory data extraction
      identified positive blood cultures occurring after 5 or more days of incubation
      at Canberra Hospital, Australia between 1 January 2001 and 31 August 2011.
      Isolates were identified as clinically significant using a pre-existing
      prospective bacteraemia database. Medical records review determined whether the
      positive result affected clinical management.Positive blood cultures after 5 or
      more days of incubation accounted for 2.65% (423/15979) of all positive blood
      cultures, although the majority were false positives or contaminants. Eighty-five
      were significant/indeterminate, representing an average of eight cases per year
      or 0.47% (85/15979) of all positive blood cultures sets. Forty-three were
      isolated for the first time, representing 1.1% of all significant/indeterminate
      blood culture episodes. Fungi and anaerobic bacteria compromised over 50% of
      isolates. In 26 cases (2.4 cases per year), the culture result led to a change in
      patient management.A 7 day incubation protocol is preferable due to late
      isolation of organisms; however, if space is required to accommodate increasing
      blood culture numbers, reducing to a 5 or 6 day protocol would miss only a small
      percentage of clinically significant isolates.

PMID- 25393256
TI  - RT-PCR testing of allograft musculoskeletal tissue: is it time for culture-based
      methods to move over?
AB  - Allograft musculoskeletal tissue samples are assessed for microbial bioburden to
      reduce the risk of post-transplant infection. Traditionally, solid agar and broth
      culture media have been used however, nucleic acid testing, such as real-time
      (RT) polymerase chain reaction (PCR), has been described as more sensitive. This
      study evaluated the recovery of low numbers of challenge organisms from
      inoculated swab and musculoskeletal biopsy samples using solid agar culture,
      cooked meat medium, blood culture bottles and a RT-PCR assay. It was found that
      broth culture methods were the most sensitive with RT-PCR unable to detect low
      numbers of bacteria from these samples. Investigation of other non-culture
      methods may be worthwhile.

PMID- 25393257
TI  - Human T-lymphotropic virus-1 serology in the Northern Territory: 2008-2011.
AB  - A retrospective observational study of human T-lymphotropic virus-1 (HTLV-1)
      serology requests made to the Northern Territory Government Pathology Service
      (NTGPS) between 2008 and 2011, was undertaken to review aspects of HTLV-1 sero
      epidemiology and performance of the assays. A total of 5686 HTLV-1 serology
      requests, representing 3555 individual patients, were received during the study
      period; 368 HTLV-1 confirmed positive serology results were identified from the
      3555 individual patients included in the sample. There was a distinct difference
      in the performance of the two antibody assays in use during this period, with the
      Serodia particle agglutination having a 5.7% indeterminate positivity rate
      compared to 18.1% indeterminate positivity rate of the Abbott HTLV 1/2 assay. We
      believe this is partially a serological anomaly related to current Australian
      western blot positive interpretative criteria, rather than false positive
      screening assay results.The majority (99.7%) of positive results occurred in
      Indigenous patients. The HTLV-1 positive rate varied geographically from a
      regional high of 51.7%, and falling inversely with distance from Central
      Australia. Patients with positive serology had a mean age of 49.9 (+/-13.9)
      years, with positivity occurring equally in males and females.

PMID- 25393258
TI  - Urgent cerebrospinal fluid analysis: is it necessary?

PMID- 25393259
TI  - Multidrug resistant, blaVEB positive Pseudomonas aeruginosa causing high
      mortality among haematology patients.

PMID- 25393260
TI  - An experience with dracunculiasis in Melbourne, Australia.

PMID- 25393261
TI  - Renal cell carcinoma with rhabdoid features and loss of INI1 expression in an
      individual without sickle cell trait.

PMID- 25393262
TI  - Adenocarcinoma arising within ectopic prostatic tissue in the urinary bladder.

PMID- 25393263
TI  - Thyroid-like follicular renal cell carcinoma: an emerging morphological variant.

PMID- 25393264
TI  - Lipid storing pyloric metaplasia of the gall bladder.

PMID- 25393265
TI  - Cytological features of pancreatic intraductal tubulopapillary neoplasm and an
      unexpected immunohistochemical profile.

PMID- 25393266
TI  - Endosalpingiosis in an axillary lymph node with synchronous micro-metastatic
      mammary carcinoma.

PMID- 25393267
TI  - Mammary analogue secretory carcinoma of minor salivary glands.

PMID- 25393268
TI  - Congenital coronary anomalies are not uncommon and consideration should be given
      to screening first degree relatives.

PMID- 25393269
TI  - Medical treatment of lower urinary tract symptoms/benign prostatic hyperplasia:
      anything new in 2015.
AB  - PURPOSE OF REVIEW: The purpose of this study is to provide an update on recent
      developments regarding the medical management of male lower urinary tract
      symptoms (LUTS). RECENT FINDINGS: Silodosin improves storage/voiding symptoms and
      nocturia and is effective within the framework of a trial without a catheter.
      5alpha-reductase inhibitors (5ARIs) are not associated with male breast cancer
      development. Alcohol consumption seems to increase the risk of high-grade
      prostate cancer under 5ARIs. The combination of alpha-blocker and 5ARIs remains a
      well established concept for benign prostatic hyperplasia/LUTS patients with an
      enhanced risk of disease progression. Tadalafil 5 mg/day monotherapy is a valid
      option particularly for men with LUTS and erectile dysfunction; the combination
      of Tadalafil 5 mg/day with a 5ARI is an interesting approach. The fixed-dose
      combination of alpha-blocker and antimuscarinic provides advantages regarding
      storage symptom improvement. This approach is currently primarily recommended as
      an add-on strategy. Mirabegron opens new horizons in the management of male LUTS
      and has no negative (but also no positive) urodynamic effects. Several
      encouraging novel approaches are currently in the experimental phase and might
      enhance our therapeutic armamentarium in the near future. SUMMARY: The recent
      literature refines our knowledge on current therapeutic options and provides
      further evidence for an individualized, risk-adapted approach for male LUTS
      mainly depending on symptoms status, comorbidities (i.e. erectile dysfunction)
      and risk of disease progression.

PMID- 25393270
TI  - GreenLight laser vaporization of the prostate: has it come of age?
AB  - PURPOSE OF REVIEW: To determine that GreenLight laser therapy is now an
      established treatment option for men with lower urinary tract symptoms (LUTS)
      associated with benign prostatic enlargement (BPE). RECENT FINDINGS: The three
      generations of the GreenLight laser, 80, 120 and 180 W, have been studied for
      efficacy and safety in the treatment of men with LUTS associated with BPE.
      Studies have also been conducted that compare outcome with transurethral
      resection of the prostate, historically considered the gold-standard treatment
      for this patient group. SUMMARY: GreenLight is an established therapeutic option
      for LUTS associated with BPE. It can be used safely and effectively in men on
      anticoagulants, in retention and with prostates of size greater than 80 ml. The
      safety and efficacy of this treatment are comparable to transurethral resection
      of the prostate.

PMID- 25393271
TI  - Lifestyle and lower urinary tract symptoms: what is the correlation in men?
AB  - PURPOSE OF REVIEW: The primary purpose of this review is to provide an overview
      of the current evidence linking lifestyle factors and lower urinary tract
      symptoms (LUTS), and their relevance in men. An extensive literature search from
      January 2013 to August 2014 was conducted, reviewed, and summarized in
      conjunction with key prior evidence. RECENT FINDINGS: The main findings from this
      review include 1) epidemiological data repeatedly show a favorable relationship
      between a healthy eating habits and regular physical activity level and a lower
      risk for LUTS or progression of LUTS, 2) certain specific nutrients or dietary
      factors may contribute to the link between diet and LUTS because of their anti
      inflammatory potential, and 3) very little research has been conducted to test
      the epidemiological findings in randomized controlled trials. SUMMARY: Rigorously
      designed clinical trials are needed to confirm the association between lifestyle
      factors and LUTS and the effect of lifestyle modification on the development or
      progression of LUTS. Nevertheless, a healthy lifestyle is known to closely relate
      with chronic diseases such as cardiovascular disease and diabetes. Thus,
      promoting a healthy lifestyle with good quality diet and regular physical
      activity is beneficial not only for potentially improving or reducing LUTS but
      also for cardiovascular and overall health. Clinicians are encouraged to include
      healthy lifestyle counseling in their routine care for patients with LUTS.

PMID- 25393272
TI  - New concepts for the treatment of male lower urinary tract symptoms.
AB  - PURPOSE OF REVIEW: New insights into how lower urinary tract symptoms (LUTS)
      develop in the presence (or absence) of benign prostatic hyperplasia (BPH) led to
      a change of terminology from BPH to LUTS, and to the revelation that several
      other (not only prostatic) molecular structures are of value in treating LUTS.
      This review aims to summarize what new we know about 'why the prostate grows
      large', and what kind of therapeutic implications that bears, and second to
      present several new compounds, which show promising results in preclinical
      testings in regards to LUTS. RECENT FINDINGS: Apart from the old concept of
      mainly hormone-dependent prostate growth, new concepts on BPH cause include
      genetic reasons, correlations with metabolic disorders, as well as an
      inflammatory origin. New pharmacological compound classes, which might be of
      value in treating LUTS, are transient receptor potential V member 1 antagonists,
      fatty acid amide hydrolase inhibitors, soluble guanylyl cyclase stimulators and
      activators, Rho-kinase inhibitors, and purinergic receptor antagonists. SUMMARY:
      New concepts on BPH cause show interesting approaches, but are still in early
      stages. They carry, however, the highest prospect to bring up causal treatments.
      Some new compounds related to LUTS are on the verge to switch 'from bench to
      bedside'.

PMID- 25393273
TI  - Genomic rearrangements in prostate cancer.
AB  - PURPOSE OF REVIEW: Genomic instability is a fundamental feature of human cancer,
      leading to the activation of oncogenes and inactivation of tumor suppressors. In
      prostate cancer (PCA), structural genomic rearrangements, resulting in gene
      fusions, amplifications, and deletions, are a critical mechanism effecting these
      alterations. Here, we review recent literature regarding the importance of
      genomic rearrangements in the pathogenesis of PCA and the potential impact on
      patient care. RECENT FINDINGS: Next-generation sequencing has revealed a striking
      abundance, complexity, and heterogeneity of genomic rearrangements in PCA. These
      recent studies have nominated a number of processes in predisposing PCA to
      genomic rearrangements, including androgen-induced transcription. SUMMARY:
      Structural rearrangements are the critical mechanism resulting in the
      characteristic genomic changes associated with PCA pathogenesis and progression.
      Future studies will determine whether the impact of these events on tumor
      phenotypes can be translated to clinical utility for patient prognosis and
      choices of management strategies.

PMID- 25393275
TI  - Outpatient surgery for lower urinary tract symptoms/benign prostatic hyperplasia:
      truth or myth?
AB  - PURPOSE OF REVIEW: Worldwide, lower urinary tract symptoms (LUTS) due to benign
      prostatic hyperplasia (BPH) is a common medical problem for aging men. Of
      patients who seek help with their symptoms, almost one-third do not respond to
      the medical therapy. These patients need a procedure that is safe, efficient, and
      durable, and at the same time carries minimal risk of side-effects. Many new
      technologies are introduced to our medical practice with the promise of being the
      ideal office-based procedure. In this review, we intend to review and discuss the
      role of three surgical procedures in an office setting. These include
      thermotherapy, 532-nm laser photo-selective vaporization of prostate, and bipolar
      plasma vaporization of prostate. RECENT FINDINGS: There are a few recent
      thermotherapy studies regarding the outcome of thermotherapy in LUTS/BPH
      patients. Data regarding the use of 532-ng laser photo-selective vaporization of
      prostate are scant but promising. The use of bipolar plasma vaporization is not
      well studied in an office setting. SUMMARY: In a select group of patients,
      thermotherapy and laser prostate surgery could be safely used to treat LUTS/BPH
      patients. Bipolar plasma vaporization is a promising technology, but its use in
      an office setting has not been completely evaluated yet.

PMID- 25393274
TI  - Serum markers in prostate cancer detection.
AB  - PURPOSE OF REVIEW: Prostate-specific antigen (PSA) testing provides significant
      benefits by reducing prostate cancer mortality, but also leads to important harms
      by detecting clinically insignificant cancers. Hence, there are urgent needs for
      complementary tools for middle-aged men with modest PSA elevations in blood. This
      review includes research on prostate cancer biomarkers in blood published from
      March 2013 through August 2014. RECENT FINDINGS: Research progress has been made
      mainly on PSA as a predictive marker and in the field of kallikrein-based tests:
      [-2] proPSA, the prostate health index, and a panel of four kallikrein markers.
      As men with PSA levels below age-median are at very low 20-year risk of
      metastatic prostate cancer, individualized screening intervals, based on PSA
      levels, may help in reducing screening costs, prostate biopsies, and detection of
      insignificant cancer. Statistical models based on kallikrein-markers in blood
      improve the specificity at modestly elevated PSA (2-10 ng/ml), eliminate
      unnecessary biopsies, and help selecting men at risk of significant prostate
      cancer for biopsy or imaging. SUMMARY: Individualized, risk-adapted PSA testing
      intervals and reflex-testing of kallikrein-markers for men with modestly
      increased PSA values may decrease the harms of screening. However, the clinical
      value of the proposed testing algorithms and additional tests awaits definitive
      confirmation in prospective trials.

PMID- 25393276
TI  - Patient compliance: the main drawback in the dermoscopic follow-up of melanocytic
      lesions.

PMID- 25393277
TI  - Application of 3-dimensional printing technology to construct an eye model for
      fundus viewing study.
AB  - OBJECTIVE: To construct a life-sized eye model using the three-dimensional (3D)
      printing technology for fundus viewing study of the viewing system. METHODS: We
      devised our schematic model eye based on Navarro's eye and redesigned some
      parameters because of the change of the corneal material and the implantation of
      intraocular lenses (IOLs). Optical performance of our schematic model eye was
      compared with Navarro's schematic eye and other two reported physical model eyes
      using the ZEMAX optical design software. With computer aided design (CAD)
      software, we designed the 3D digital model of the main structure of the physical
      model eye, which was used for three-dimensional (3D) printing. Together with the
      main printed structure, polymethyl methacrylate(PMMA) aspherical cornea, variable
      iris, and IOLs were assembled to a physical eye model. Angle scale bars were
      glued from posterior to periphery of the retina. Then we fabricated other three
      physical models with different states of ammetropia. Optical parameters of these
      physical eye models were measured to verify the 3D printing accuracy. RESULTS: In
      on-axis calculations, our schematic model eye possessed similar size of spot
      diagram compared with Navarro's and Bakaraju's model eye, much smaller than
      Arianpour's model eye. Moreover, the spherical aberration of our schematic eye
      was much less than other three model eyes. While in off- axis simulation, it
      possessed a bit higher coma and similar astigmatism, field curvature and
      distortion. The MTF curves showed that all the model eyes diminished in
      resolution with increasing field of view, and the diminished tendency of
      resolution of our physical eye model was similar to the Navarro's eye. The
      measured parameters of our eye models with different status of ametropia were in
      line with the theoretical value. CONCLUSIONS: The schematic eye model we designed
      can well simulate the optical performance of the human eye, and the fabricated
      physical one can be used as a tool in fundus range viewing research.

PMID- 25393278
TI  - The COP9 signalosome converts temporal hormone signaling to spatial restriction
      on neural competence.
AB  - During development, neural competence is conferred and maintained by integrating
      spatial and temporal regulations. The Drosophila sensory bristles that detect
      mechanical and chemical stimulations are arranged in stereotypical positions. The
      anterior wing margin (AWM) is arrayed with neuron-innervated sensory bristles,
      while posterior wing margin (PWM) bristles are non-innervated. We found that the
      COP9 signalosome (CSN) suppresses the neural competence of non-innervated
      bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron
      innervated, which is attributed to sustained expression of the neural-determining
      factor Senseless (Sens). The CSN suppresses Sens through repression of the
      ecdysone signaling target gene broad (br) that encodes the BR-Z1 transcription
      factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is
      initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and
      termination of the neural competence of PWM bristles. The role of ecdysone
      signaling to repress br after the prepupa-to-pupa transition is distinct from its
      conventional role in activation, and requires CSN deneddylating activity and
      multiple cullins, the major substrates of deneddylation. Several CSN subunits
      physically associate with ecdysone receptors to represses br at the
      transcriptional level. We propose a model in which nuclear hormone receptors
      cooperate with the deneddylation machinery to temporally shutdown downstream
      target gene expression, conferring a spatial restriction on neural competence at
      the PWM. 

PMID- 25393279
TI  - MR-based morphometry of the posterior fossa in fetuses with neural tube defects
      of the spine.
AB  - OBJECTIVES: In cases of "spina bifida," a detailed prenatal imaging assessment of
      the exact morphology of neural tube defects (NTD) is often limited. Due to the
      diverse clinical prognosis and prenatal treatment options, imaging parameters
      that support the prenatal differentiation between open and closed neural tube
      defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the
      clivus-supraocciput angle (CSA) and the maximum transverse diameter of the
      posterior fossa (TDPF) as morphometric parameters to aid in the reliable
      diagnosis of either ONTDs or CNTDs. METHODS: The TDPF and the CSA of 238 fetuses
      (20-37 GW, mean: 28.36 GW) with a normal central nervous system, 44 with ONTDS,
      and 13 with CNTDs (18-37 GW, mean: 24.3 GW) were retrospectively measured using
      T2-weighted 1.5 Tesla MR -sequences. RESULTS: Normal fetuses showed a significant
      increase in the TDPF (r = .956; p<.001) and CSA (r = .714; p<.001) with
      gestational age. In ONTDs the CSA was significantly smaller (p<.001) than in
      normal controls and CNTDs, whereas in CNTDs the CSA was not significantly smaller
      than in controls (p = .160). In both ONTDs and in CNTDs the TDPF was
      significantly different from controls (p<.001). CONCLUSIONS: The skull base
      morphology in fetuses with ONTDs differs significantly from cases with CNTDs and
      normal controls. This is the first study to show that the CSA changes during
      gestation and that it is a reliable imaging biomarker to distinguish between
      ONTDs and CNTDs, independent of the morphology of the spinal defect.

PMID- 25393280
TI  - Clinical application of estimating hepatitis B virus quasispecies complexity by
      massive sequencing: correlation between natural evolution and on-treatment
      evolution.
AB  - AIM: To evaluate HBV quasispecies (QA) complexity in the preCore/Core regions in
      relation to HBeAg status, and explore QA changes under natural evolution and
      nucleoside analogue (NUC) treatment. METHODS: Ultra-deep pyrosequencing of HBV
      preCore/Core regions in 30 sequential samples (baseline [diagnosis], treatment
      free, and treatment-nonresponse) from 10 retrospectively selected patients
      grouped according to HBeAg status over time: HBeAg+ (N = 4), HBeAg- (N = 2), and
      fluctuating HBeAg (transient seroreversion/seroconversion pattern) (N = 4). QA
      complexity was defined by Shannon entropy, mutation frequency, nucleotide
      diversity, and mutation frequency of amino acids (MfAA) in preCore and Core.
      RESULTS: The QA was less complex in HBeAg+ than in HBeAg- or fluctuating HBeAg.
      High complexity in preCore was associated with decreased viral replication
      (preCore MfAA negatively correlated with HBV-DNA, p = 0.005). QA complexity in
      the treatment-free period negatively correlated with values seen during
      treatment. Specific variants were mainly selected in the Core region in HBeAg-
      and fluctuating HBeAg patients, suggesting higher immune pressure than in HBeAg+.
      CONCLUSIONS: The negative correlation between QA natural evolution and on
      treatment evolution indicates the importance of pre-treatment QA study to predict
      QA changes in NUC nonresponders. Study of QA complexity could be useful for
      managing HBV infection.

PMID- 25393281
TI  - Incidence of HIV-associated tuberculosis among individuals taking combination
      antiretroviral therapy: a systematic review and meta-analysis.
AB  - BACKGROUND: Knowledge of tuberculosis incidence and associated factors is
      required for the development and evaluation of strategies to reduce the burden of
      HIV-associated tuberculosis. METHODS: Systematic literature review and meta
      analysis of tuberculosis incidence rates among HIV-infected individuals taking
      combination antiretroviral therapy. RESULTS: From PubMed, EMBASE and Global Index
      Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and
      11 from low tuberculosis burden settings) were included in the qualitative review
      and 33 in the quantitative review. Cohorts from high/intermediate burden settings
      were smaller in size, had lower median CD4 cell counts at study entry and fewer
      person-years of follow up. Tuberculosis incidence rates were higher in studies
      from Sub-Saharan Africa and from World Bank low/middle income countries.
      Tuberculosis incidence rates decreased with increasing CD4 count at study entry
      and duration on combination antiretroviral therapy. Summary estimates of
      tuberculosis incidence among individuals on combination antiretroviral therapy
      were higher for cohorts from high/intermediate burden settings compared to those
      from the low tuberculosis burden settings (4.17 per 100 person-years [95%
      Confidence Interval (CI) 3.39-5.14 per 100 person-years] vs. 0.4 per 100 person
      years [95% CI 0.23-0.69 per 100 person-years]) with significant heterogeneity
      observed between the studies. CONCLUSIONS: Tuberculosis incidence rates were high
      among individuals on combination antiretroviral therapy in high/intermediate
      burden settings. Interventions to prevent tuberculosis in this population should
      address geographical, socioeconomic and individual factors such as low CD4 counts
      and prior history of tuberculosis.

PMID- 25393282
TI  - TBL2 is a novel PERK-binding protein that modulates stress-signaling and cell
      survival during endoplasmic reticulum stress.
AB  - Under ER stress, PKR-like ER-resident kinase (PERK) phosphorylates translation
      initiation factor eIF2alpha, resulting in repression of global protein synthesis
      and concomitant upregulation of the translation of specific mRNAs such as
      activating transcription factor 4 (ATF4). This PERK function is important for
      cell survival under ER stress and poor nutrient conditions. However, mechanisms
      of the PERK signaling pathway are not thoroughly understood. Here we identify
      transducin (beta)-like 2 (TBL2) as a novel PERK-binding protein. We found that
      TBL2 is an ER-localized type-I transmembrane protein and preferentially binds to
      the phosphorylated form of PERK, but not another eIF2alpha kinase GCN2 or ER
      resident kinase IRE1, under ER stress. Immunoprecipitation analysis using various
      deletion mutants revealed that TBL2 interacts with PERK via the N-terminus
      proximal region and also associates with eIF2alpha via the WD40 domain. In
      addition, TBL2 knockdown can lead to impaired ATF4 induction under ER stress or
      poor nutrient conditions such as glucose and oxygen deprivation. Consistently,
      TBL2 knockdown rendered cells vulnerable to stresses similarly to PERK knockdown.
      Thus, TBL2 serves as a potential regulator of the PERK pathway. 

PMID- 25393283
TI  - Influence of exercise on bone remodeling-related hormones and cytokines in
      ovariectomized rats: a model of postmenopausal osteoporosis.
AB  - This study aims to explore the effects of exercise on postmenopausal osteoporosis
      and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar
      female rats were randomly divided into five groups: (1) control group, (2) sham
      operated group, (3) OVX (Ovariectomy) group, (4) DES-OVX (Diethylstilbestrol-OVX)
      group, and (5) Ex-OVX (Exercise-OVX) group. The rat osteoporosis model was
      established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters
      every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%),
      total resorption surface (TRS%), trabecular formation surface (TFS%),
      mineralization rate (MAR), bone cortex mineralization rate (mAR), and osteoid
      seam width (OSW) were determined by bone histomorphometry. The mRNA and protein
      levels of interleukin-1beta (IL-1beta2), interleukin-6 (IL-6), and cyclooxygenase
      2 (Cox-2) were determined by in situ hybridization and immunohistochemistry,
      respectively. Serum levels of estrogen estradiol (E2), calcitonin (CT),
      osteocalcin (BGP), and parathyroid hormone (PTH) were determined by ELISA assays.
      The investigation revealed that compared to the control and the sham-operated
      groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but
      much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed
      increased TBV% and serum levels of E2 and CT compared to the OVX group.
      Ovariectomy also led to a significant increase in IL-1beta mRNA and protein
      levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In
      addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6
      mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the
      study suggests that exercise can significantly increase bone mass in
      postmenopausal osteoporosis rat models by inhibiting bone resorption and
      increasing bone formation, especially in trabecular bones. 

PMID- 25393285
TI  - Global microRNA modification in cotton (Gossypium hirsutum L.).
AB  - MicroRNAs (miRNAs) are small noncoding RNAs participating in versatile biological
      processes via post-transcriptionally gene regulation. However, how miRNAs are
      modified or degraded remains unknown, despite years of studies have unravelled
      much details of miRNA biogenesis and function. Here, we systematically
      investigated miRNA modification using six small RNA sequencing libraries
      generated from cotton seedling as well as cotton fibre at five developmental
      stages. Our results show that 1-2-nt truncation and addition on both 5' and 3'
      ends of miRNAs are the major modification forms. The 5' and 3' end miRNA
      modification was almost equal in the six development stages. Truncation was more
      common than addition on both 5' and 3' end. Structure analysis of the 5' and 3'
      ends of miRNAs and isomiRs shows that uridine is the preferential nucleotide at
      the first position of both 5' and 3' ends. According to analysis of nucleotides
      truncated and tailed from miRNAs, both miRNAs and isomiRs share a similar
      positional structure distribution at their 5' and 3' ends, respectively.
      Furthermore, opposite to previous reports, cytodine is more frequently truncated
      and tailed from the two ends of isomiRs, implying existence of a complex cytodine
      balance in isomiRs. Comparison of isomiR expression shows differential miRNA
      modification amongst the six developmental stages in terms of selective
      modification form, development-dependent modification and differential expression
      abundance. Our results globally uncovered miRNA modification features in cotton,
      which could contribute us to understanding miRNA's postmature modification and
      its regulatory function. 

PMID- 25393286
TI  - Asymptotic properties of Pearson's rank-variate correlation coefficient under
      contaminated Gaussian model.
AB  - This paper investigates the robustness properties of Pearson's rank-variate
      correlation coefficient (PRVCC) in scenarios where one channel is corrupted by
      impulsive noise and the other is impulsive noise-free. As shown in our previous
      work, these scenarios that frequently encountered in radar and/or sonar, can be
      well emulated by a particular bivariate contaminated Gaussian model (CGM). Under
      this CGM, we establish the asymptotic closed forms of the expectation and
      variance of PRVCC by means of the well known Delta method. To gain a deeper
      understanding, we also compare PRVCC with two other classical correlation
      coefficients, i.e., Spearman's rho (SR) and Kendall's tau (KT), in terms of the
      root mean squared error (RMSE). Monte Carlo simulations not only verify our
      theoretical findings, but also reveal the advantage of PRVCC by an example of
      estimating the time delay in the particular impulsive noise environment. 

PMID- 25393288
TI  - p53- and ERK7-dependent ribosome surveillance response regulates Drosophila
      insulin-like peptide secretion.
AB  - Insulin-like signalling is a conserved mechanism that coordinates animal growth
      and metabolism with nutrient status. In Drosophila, insulin-producing median
      neurosecretory cells (IPCs) regulate larval growth by secreting insulin-like
      peptides (dILPs) in a diet-dependent manner. Previous studies have shown that
      nutrition affects dILP secretion through humoral signals derived from the fat
      body. Here we uncover a novel mechanism that operates cell autonomously in the
      IPCs to regulate dILP secretion. We observed that impairment of ribosome
      biogenesis specifically in the IPCs strongly inhibits dILP secretion, which
      consequently leads to reduced body size and a delay in larval development. This
      response is dependent on p53, a known surveillance factor for ribosome
      biogenesis. A downstream effector of this growth inhibitory response is an
      atypical MAP kinase ERK7 (ERK8/MAPK15), which is upregulated in the IPCs
      following impaired ribosome biogenesis as well as starvation. We show that ERK7
      is sufficient and essential to inhibit dILP secretion upon impaired ribosome
      biogenesis, and it acts epistatically to p53. Moreover, we provide evidence that
      p53 and ERK7 contribute to the inhibition of dILP secretion upon starvation.
      Thus, we conclude that a cell autonomous ribosome surveillance response, which
      leads to upregulation of ERK7, inhibits dILP secretion to impede tissue growth
      under limiting dietary conditions.

PMID- 25393287
TI  - Zinc supplementation inhibits complement activation in age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      Western world. AMD is a multifactorial disorder but complement-mediated
      inflammation at the level of the retina plays a pivotal role. Oral zinc
      supplementation can reduce the progression of AMD but the precise mechanism of
      this protective effect is as yet unclear. We investigated whether zinc
      supplementation directly affects the degree of complement activation in AMD and
      whether there is a relation between serum complement catabolism during zinc
      administration and the complement factor H (CFH) gene or the Age-Related
      Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study,
      72 randomly selected AMD patients in various stages of AMD received a daily
      supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months.
      Serum complement catabolism-defined as the C3d/C3 ratio-was measured at baseline,
      throughout the three months of supplementation and after discontinuation of zinc
      administration. Additionally, downstream inhibition of complement catabolism was
      evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the
      effect of zinc on complement activation in vitro. AMD patients with high levels
      of complement catabolism at baseline exhibited a steeper decline in serum
      complement activation (p<0.001) during the three month zinc supplementation
      period compared to patients with low complement levels. There was no significant
      association of change in complement catabolism and CFH and ARMS2 genotype. In
      vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays
      and membrane attack complex (MAC) deposition on RPE cells. This study provides
      evidence that daily administration of 50 mg zinc sulphate can inhibit complement
      catabolism in AMD patients with increased complement activation. This could
      explain part of the mechanism by which zinc slows AMD progression. TRIAL
      REGISTRATION: The Netherlands National Trial Register NTR2605.

PMID- 25393289
TI  - Psychometric properties of the participation scale among former buruli ulcer
      patients in Ghana and Benin.
AB  - BACKGROUND: Buruli ulcer is a stigmatising disease treated with antibiotics and
      wound care, and sometimes surgical intervention is necessary. Permanent
      limitations in daily activities are a common long term consequence. It is unknown
      to what extent patients perceive problems in participation in social activities.
      The psychometric properties of the Participation Scale used in other disabling
      diseases, such as leprosy, was assessed for use in former Buruli ulcer patients.
      METHODS: Former Buruli ulcer patients in Ghana and Benin, their relatives, and
      healthy community controls were interviewed using the Participation Scale, Buruli
      Ulcer Functional Limitation Score, and the Explanatory Model Interview Catalogue
      to measure stigma. The Participation Scale was tested for the following
      psychometric properties: discrimination, floor and ceiling effects, internal
      consistency, inter-item correlation, item-total correlation and construct
      validity. RESULTS: In total 386 participants (143 former Buruli ulcer patients
      with their relatives (137) and 106 community controls) were included in the
      study. The Participation Scale displayed good discrimination between former
      Buruli ulcer patients and healthy community controls. No floor and ceiling
      effects were found. Internal consistency (Cronbach's alpha) was 0.88. In Ghana,
      mean inter-item correlation of 0.29 and item-total correlations ranging from 0.10
      to 0.69 were found while in Benin, a mean inter-item correlation of 0.28 was
      reported with item-total correlations ranging from -0.08 to 0.79. With respect to
      construct validity, 4 out of 6 hypotheses were not rejected, though correlations
      between various constructs differed between countries. CONCLUSION: The results
      indicate the Participation Scale has acceptable psychometric properties and can
      be used for Buruli ulcer patients in Ghana and Benin. Future studies can use this
      Participation Scale to evaluate the long term restrictions in participation in
      daily social activities of former BU patients.

PMID- 25393291
TI  - NAD(P)H-hydrate dehydratase- a metabolic repair enzyme and its role in Bacillus
      subtilis stress adaptation.
AB  - BACKGROUND: One of the strategies for survival stress conditions in bacteria is a
      regulatory adaptive system called general stress response (GSR), which is
      dependent on the SigB transcription factor in Bacillus sp. The GSR is one of the
      largest regulon in Bacillus sp., including about 100 genes; however, most of the
      genes that show changes in expression during various stresses have not yet been
      characterized or assigned a biochemical function for the encoded proteins.
      Previously, we characterized the Bacillus subtilis168 osmosensitive mutant,
      defective in the yxkO gene (encoding a putative ribokinase), which was recently
      assigned in vitro as an ADP/ATP-dependent NAD(P)H-hydrate dehydratase and was
      demonstrated to belong to the SigB operon. METHODS AND RESULTS: We show the
      impact of YxkO on the activity of SigB-dependent Pctc promoter and adaptation to
      osmotic and ethanol stress and potassium limitation respectively. Using a 2DE
      approach, we compare the proteomes of WT and mutant strains grown under
      conditions of osmotic and ethanol stress. Both stresses led to changes in the
      protein level of enzymes that are involved in motility (flagellin), citrate cycle
      (isocitrate dehydrogenase, malate dehydrogenase), glycolysis (phosphoglycerate
      kinase), and decomposition of Amadori products (fructosamine-6-phosphate
      deglycase). Glutamine synthetase revealed a different pattern after osmotic
      stress. The patterns of enzymes for branched amino acid metabolism and cell wall
      synthesis (L-alanine dehydrogenase, aspartate-semialdehyde dehydrogenase, ketol
      acid reductoisomerase) were altered after ethanol stress. CONCLUSION: We
      performed the first characterization of a Bacillus subtilis168 knock-out mutant
      in the yxkO gene that encodes a metabolite repair enzyme. We show that such
      enzymes could play a significant role in the survival of stressed cells.

PMID- 25393292
TI  - Differential sensitivity of epithelial cells to extracellular matrix in polarity
      establishment.
AB  - Establishment of apical-basal polarity is crucial for epithelial sheets that form
      a compartment in the body, which function to maintain the environment in the
      compartment. Effects of impaired polarization are easily observed in three
      dimensional (3-D) culture systems rather than in two-dimensional (2-D) culture
      systems. Although the mechanisms for establishing the polarity are not completely
      understood, signals from the extracellular matrix (ECM) are considered to be
      essential for determining the basal side and eventually generating polarity in
      the epithelial cells. To elucidate the common features and differences in
      polarity establishment among various epithelial cells, we analyzed the formation
      of epithelial apical-basal polarity using three cell lines of different origin:
      MDCK II cells (dog renal tubules), EpH4 cells (mouse mammary gland), and R2/7
      cells (human colon) expressing wild-type alpha-catenin (R2/7 alpha-Cate cells).
      These cells showed clear apical-basal polarity in 2-D cultures. In 3-D cultures,
      however, each cell line displayed different responses to the same ECM. In MDCK II
      cells, spheroids with a single lumen formed in both Matrigel and collagen gel. In
      R2/7 alpha-Cate cells, spheroids showed similar apical-basal polarity as that
      seen in MDCK II cells, but had multiple lumens. In EpH4 cells, the spheroids
      displayed an apical-basal polarity that was opposite to that seen in the other
      two cell types in both ECM gels, at least during the culture period. On the other
      hand, the three cell lines showed the same apical-basal polarity both in 2-D
      cultures and in 3-D cultures using the hanging drop method. The three lines also
      had similar cellular responses to ECM secreted by the cells themselves.
      Therefore, appropriate culture conditions should be carefully determined in
      advance when using various epithelial cells to analyze cell polarity or 3-D
      morphogenesis. 

PMID- 25393293
TI  - Pattern of tick aggregation on mice: larger than expected distribution tail
      enhances the spread of tick-borne pathogens.
AB  - The spread of tick-borne pathogens represents an important threat to human and
      animal health in many parts of Eurasia. Here, we analysed a 9-year time series of
      Ixodes ricinus ticks feeding on Apodemus flavicollis mice (main reservoir
      competent host for tick-borne encephalitis, TBE) sampled in Trentino (Northern
      Italy). The tail of the distribution of the number of ticks per host was fitted
      by three theoretical distributions: Negative Binomial (NB), Poisson-LogNormal
      (PoiLN), and Power-Law (PL). The fit with theoretical distributions indicated
      that the tail of the tick infestation pattern on mice is better described by the
      PL distribution. Moreover, we found that the tail of the distribution
      significantly changes with seasonal variations in host abundance. In order to
      investigate the effect of different tails of tick distribution on the invasion of
      a non-systemically transmitted pathogen, we simulated the transmission of a TBE
      like virus between susceptible and infective ticks using a stochastic model.
      Model simulations indicated different outcomes of disease spreading when
      considering different distribution laws of ticks among hosts. Specifically, we
      found that the epidemic threshold and the prevalence equilibria obtained in
      epidemiological simulations with PL distribution are a good approximation of
      those observed in simulations feed by the empirical distribution. Moreover, we
      also found that the epidemic threshold for disease invasion was lower when
      considering the seasonal variation of tick aggregation. 

PMID- 25393295
TI  - Abstracts of the 30th Turkish cardiology congress with international
      participation. October 23-26, 2014, istanbul, Turkey.

PMID- 25393290
TI  - In vivo experiments reveal the good, the bad and the ugly faces of sFlt-1 in
      pregnancy.
AB  - OBJECTIVE: Soluble fms-like tyrosine kinase (sFlt)-1-e15a, a primate-specific
      sFlt-1-isoform most abundant in the human placenta in preeclampsia, can induce
      preeclampsia in mice. This study compared the effects of full-length human
      (h)sFlt-1-e15a with those of truncated mouse (m)sFlt-1(1-3) used in previous
      preeclampsia studies on pregnancy outcome and clinical symptoms in preeclampsia.
      METHODS: Mice were injected with adenoviruses or fiber-mutant adenoviruses
      overexpressing hsFlt-1-e15a, msFlt-1(1-3) or control GFP under the CMV or CYP19A1
      promoters on gestational day 8 (GD8) and GD11. Placentas and pups were delivered
      by cesarean section, and dams were monitored postpartum. Blood pressure was
      telemetrically recorded. Urine samples were collected with cystocentesis and
      examined for albumin/creatinine ratios. Tissue specimens were evaluated for
      transgene as well as endogenous mFlt-1 and msFlt-1-i13 expression. H&E-, Jones-
      and PAS-stained kidney sections were histopathologically examined. Placental GFP
      expression and aortic ring assays were investigated with confocal microscopy.
      RESULTS: Mean arterial blood pressure (MAP) was elevated before delivery in hsFlt
      1-e15a-treated mice compared to controls (GD18: DeltaMAP = 7.8 mmHg, p = 0.009),
      while DeltaMAP was 12.8 mmHg (GD18, p = 0.005) in msFlt-1(1-3)-treated mice.
      Urine albumin/creatinine ratio was higher in hsFlt-1-e15a-treated mice than in
      controls (GD18, p = 0.04; PPD8, p = 0.03), and msFlt-1(1-3)-treated mice had
      marked proteinuria postpartum (PPD8, p = 4 * 10(-5)). Focal glomerular changes
      were detected in hsFlt-1-e15a and msFlt-1(1-3)-treated mice. Aortic ring
      microvessel outgrowth was decreased in hsFlt-1-e15a (p = 0.007) and msFlt-1(1-3)
      treated (p = 0.02) mice. Full-length msFlt-1-i13 expression was unique for the
      placenta. In hsFlt-1-e15a-treated mice, the number of pups (p = 0.046), total
      weight of living pups (p = 0.04) and maternal weights (p = 0.04) were higher than
      in controls. These differences were not observed in truncated msFlt-1(1-3)
      treated mice. CONCLUSIONS: Truncated msFlt-1(1-3) simulated the preeclampsia
      promoting effects of full-length hsFlt-1. MsFlt-1(1-3) had strong effect on
      maternal endothelium but not on placentas and embryos. In contrast, hsFlt-1-e15a
      induced preeclampsia-like symptoms; however, it also increased litter size. In
      accord with the predominant placental expression of hsFlt-1-e15a and msFlt-1-i13,
      full-length sFlt-1 may have a role in the regulation of embryonic development.
      These observations point to the difference in the biological effects of full
      length and truncated sFlt-1 and the changes in the effect of full-length sFlt-1
      during pregnancy, and may have important implications in the management of
      preeclampsia.

PMID- 25393294
TI  - Comparison of longitudinal in vivo measurements of retinal nerve fiber layer
      thickness and retinal ganglion cell density after optic nerve transection in rat.
AB  - PURPOSE: To determine the relationship between longitudinal in vivo measurements
      of retinal nerve fiber layer thickness (RNFLT) and retinal ganglion cell (RGC)
      density after unilateral optic nerve transection (ONT). METHODS: Nineteen adult
      Brown-Norway rats were studied; N = 10 ONT plus RGC label, N = 3 ONT plus vehicle
      only (sans label), N = 6 sham ONT plus RGC label. RNFLT was measured by spectral
      domain optical coherence tomography (SD-OCT) at baseline then weekly for 1 month.
      RGCs were labeled by retrograde transport of fluorescently conjugated cholera
      toxin B (CTB) from the superior colliculus 48 hours prior to ONT or sham surgery.
      RGC density measurements were obtained by confocal scanning laser ophthalmoscopy
      (CSLO) at baseline and weekly for 1 month. RGC density and reactivity of
      microglia (anti-Iba1) and astrocytes (anti-GFAP) were determined from post mortem
      fluorescence microscopy of whole-mount retinae. RESULTS: RNFLT decreased after
      ONT by 17% (p<0.05), 30% (p<0.0001) and 36% (p<0.0001) at weeks 2, 3 and 4. RGC
      density decreased after ONT by 18%, 69%, 85% and 92% at weeks 1, 2, 3 and 4
      (p<0.0001 each). RGC density measured in vivo at week 4 and post mortem by
      microscopy were strongly correlated (R = 0.91, p<0.0001). In vivo measures of
      RNFLT and RGC density were strongly correlated (R = 0.81, p<0.0001). In ONT-CTB
      labeled fellow eyes, RNFLT increased by 18%, 52% and 36% at weeks 2, 3 and 4
      (p<0.0001), but did not change in fellow ONT-eyes sans CTB. Microgliosis was
      evident in the RNFL of the ONT-CTB fellow eyes, exceeding that observed in other
      fellow eyes. CONCLUSIONS: In vivo measurements of RNFLT and RGC density are
      strongly correlated and can be used to monitor longitudinal changes after optic
      nerve injury. The strong fellow eye effect observed in eyes contralateral to ONT,
      only in the presence of CTB label, consisted of a dramatic increase in RNFLT
      associated with retinal microgliosis.

PMID- 25393296
TI  - Effect of Interpersonal and Cognitive Stressors on Habituation and the Utility of
      Heart Rate Variability to Measure Habituation.
AB  - Habituation is a decrease in responding to a repeated stimulus. Operant
      responding and salivation measure habituation in eating behaviour research.
      Stress may increase eating by acting as a distractor, yielding spontaneous
      recovery and prolonging responding for food. Our research tested differences in
      the ability of cognitive and interpersonal stressors to recover responding for
      food. We also tested heart rate variability (HRV) as a measure of habituation.
      Twenty women worked for portions of macaroni and cheese for 15 trials on three
      separate laboratory visits. Between the 12th and 13th trial, one of three
      different stressor types (speech, stroop and subtraction) was presented during
      each visit. HRV was measured continuously throughout the laboratory visits.
      Responding for food declined across the 12 trials with no difference in rate of
      habituation by visit (p > 0.8) There was no difference between stressor type in
      the magnitude of spontaneous recovery after each stressor (p > 0.8). Rates of
      habituation of HRV variables correlated (p < 0.02) with the rate of operant
      responding habituation. Cognitive and interpersonal stressors do not differ in
      their ability to recover reduced responding for food. HRV variables may measure
      habituation to food similar to operant responding. Copyright (c) 2014 John Wiley
      & Sons, Ltd.

PMID- 25393298
TI  - What we expect is not always what we get: evidence for both the direction-of
      change and the specific-stimulus hypotheses of auditory attentional capture.
AB  - Participants were requested to respond to a sequence of visual targets while
      listening to a well-known lullaby. One of the notes in the lullaby was
      occasionally exchanged with a pattern deviant. Experiment 1 found that deviants
      capture attention as a function of the pitch difference between the deviant and
      the replaced/expected tone. However, when the pitch difference between the
      expected tone and the deviant tone is held constant, a violation to the direction
      of-pitch change across tones can also capture attention (Experiment 2). Moreover,
      in more complex auditory environments, wherein it is difficult to build a
      coherent neural model of the sound environment from which expectations are
      formed, deviations can capture attention but it appears to matter less whether
      this is a violation from a specific stimulus or a violation of the current
      direction-of-change (Experiment 3). The results support the expectation violation
      account of auditory distraction and suggest that there are at least two different
      expectations that can be violated: One appears to be bound to a specific stimulus
      and the other would seem to be bound to a more global cross-stimulus rule such as
      the direction-of-change based on a sequence of preceding sound events. Factors
      like base-rate probability of tones within the sound environment might become the
      driving mechanism of attentional capture--rather than violated expectations--in
      complex sound environments.

PMID- 25393297
TI  - Delineation of early and later adult onset depression by diffusion tensor
      imaging.
AB  - BACKGROUND: Due to a lack of evidence, there is no consistent age of onset to
      define early onset (EO) versus later onset (LO) major depressive disorder (MDD).
      Fractional anisotropy (FA), derived from diffusion tensor imaging (DTI), has been
      widely used to study neuropsychiatric disorders by providing information about
      the brain circuitry, abnormalities of which might facilitate the delineation of
      EO versus LO MDD. METHOD: In this study, 61 pairs of untreated, non-elderly,
      first-episode MDD patients and healthy controls (HCs) aged 18-45 years old
      received DTI scans. The voxel-based analysis method (VBM), classification
      analysis, using the Statistical Package for the Social Sciences (SPSS), and
      regression analyses were used to determine abnormal FA clusters and their
      correlations with age of onset and clinical symptoms. RESULTS: Classification
      analysis suggested in the best model that there were two subgroups of MDD
      patients, delineated by an age of onset of 30 years old, by which MDD patients
      could be divided into EO (18-29 years old) and LO (30-45 years old) groups. LO
      MDD was characterized by decreased FA, especially in the white matter (WM) of the
      fronto-occipital fasciculus and posterior limb of internal capsule, with a
      negative correlation with the severity of depressive symptoms; in marked
      contrast, EO MDD showed increased FA, especially in the WM of the corpus
      callosum, corticospinal midbrain and inferior fronto-occipital fasciculus, while
      FA of the WM near the midbrain had a positive correlation with the severity of
      depressive symptoms. CONCLUSION: Specific abnormalities of the brain circuitry in
      EO vs. LO MDD were delineated by an age of onset of 30 years old, as demonstrated
      by distinct abnormal FA clusters with opposite correlations with clinical
      symptoms. This DTI study supported the evidence of an exact age for the
      delineation of MDD, which could have broad multidisciplinary importance. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00703742.

PMID- 25393299
TI  - Hematopoietic stem/progenitor cell sources to generate reticulocytes for
      Plasmodium vivax culture.
AB  - The predilection of Plasmodium vivax (P. vivax) for reticulocytes is a major
      obstacle for its establishment in a long-term culture system, as this requires a
      continuous supply of large quantities of reticulocytes, representing only 1-2% of
      circulating red blood cells. We here compared the production of reticulocytes
      using an established in vitro culture system from three different sources of
      hematopoietic stem/progenitor cells (HSPC), i.e. umbilical cord blood (UCB), bone
      marrow (BM) and adult peripheral blood (PB). Compared to CD34+-enriched
      populations of PB and BM, CD34+-enriched populations of UCB produced the highest
      amount of reticulocytes that could be invaded by P. vivax. In addition, when
      CD34+-enriched cells were first expanded, a further extensive increase in
      reticulocytes was seen for UCB, to a lesser degree BM but not PB. As invasion by
      P. vivax was significantly better in reticulocytes generated in vitro, we also
      suggest that P. vivax may have a preference for invading immature reticulocytes,
      which should be confirmed in future studies. 

PMID- 25393300
TI  - Population structure of Geosmithia morbida, the causal agent of thousand cankers
      disease of walnut trees in the United States.
AB  - The ascomycete Geosmithia morbida and the walnut twig beetle Pityophthorus
      juglandis are associated with thousand cankers disease of Juglans (walnut) and
      Pterocarya (wingnut). The disease was first reported in the western United States
      (USA) on several Juglans species, but has been found more recently in the eastern
      USA in the native range of the highly susceptible Juglans nigra. We performed a
      comprehensive population genetic study of 209 G. morbida isolates collected from
      Juglans and Pterocarya from 17 geographic regions distributed across 12 U.S.
      states. The study was based on sequence typing of 27 single nucleotide
      polymorphisms from three genomic regions and genotyping with ten microsatellite
      primer pairs. Using multilocus sequence-typing data, 197 G. morbida isolates were
      placed into one of 57 haplotypes. In some instances, multiple haplotypes were
      recovered from isolates collected on the same tree. Twenty-four of the haplotypes
      (42%) were recovered from more than one isolate; the two most frequently
      occurring haplotypes (H02 and H03) represented 36% of all isolates. These two
      haplotypes were abundant in California, but were not recovered from Arizona or
      New Mexico. G. morbida population structure was best explained by four
      genetically distinct groups that clustered into three geographic regions. Most of
      the haplotypes isolated from the native range of J. major (Arizona and New
      Mexico) were found in those states only or present in distinct genetic clusters.
      There was no evidence of sexual reproduction or genetic recombination in any
      population. The scattered distribution of the genetic clusters indicated that G.
      morbida was likely disseminated to different regions at several times and from
      several sources. The large number of haplotypes observed and the genetic
      complexity of G. morbida indicate that it evolved in association with at least
      one Juglans spp. and the walnut twig beetle long before the first reports of the
      disease. 

PMID- 25393302
TI  - Effect of different fibre sources on performance, carcass characteristics and
      gastrointestinal tract development of growing Greylag geese.
AB  - 1. The effects of different fibre sources on the growth performance, carcass
      characteristics and gastrointestinal tract development were studied in growing
      Greylag geese (Anser anser). 2. Four experimental diets were formulated with corn
      (maize) straw silage (CSS), steam-exploded corn (maize) straw, steam-exploded
      wheat straw, and steam-exploded rice straw as fibre sources. A total of 224 male
      Greylag geese at 28 d of age were randomly assigned to one of the 4 experimental
      diets. 3. The birds fed on the CSS diets had higher average daily feed intakes
      than those fed on the steam-exploded straws. However, the 4 treatments had
      similar average daily gain, which contributed to significant differences in feed
      conversion ratios. The different fibre sources had no significant effects on the
      carcass characteristics. 4. The CSS-fed birds had larger gizzards and lower
      relative length of the caeca than the other three groups. However, the relative
      weights and lengths of the other gut segments, the relative weights of major
      organs and the pH values of the gastrointestinal contents were similar between
      the 4 treatments. It was concluded that straw fibres with different physico
      chemical properties exerted an effect on daily feed intake and gastrointestinal
      development, especially for the gizzard. The pretreatment of straw had a large
      effect on utilisation efficiency and animal performance. Steam explosion is a
      promising straw pretreatment for inclusion in diets for geese.

PMID- 25393303
TI  - The global one health paradigm: challenges and opportunities for tackling
      infectious diseases at the human, animal, and environment interface in low
      resource settings.
AB  - Zoonotic infectious diseases have been an important concern to humankind for more
      than 10,000 years. Today, approximately 75% of newly emerging infectious diseases
      (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic,
      socioeconomic, and climatic factors. These interrelated driving forces make it
      difficult to predict and to prevent zoonotic EIDs. Although significant
      improvements in environmental and medical surveillance, clinical diagnostic
      methods, and medical practices have been achieved in the recent years, zoonotic
      EIDs remain a major global concern, and such threats are expanding, especially in
      less developed regions. The current Ebola epidemic in West Africa is an extreme
      stark reminder of the role animal reservoirs play in public health and reinforces
      the urgent need for globally operationalizing a One Health approach. The complex
      nature of zoonotic diseases and the limited resources in developing countries are
      a reminder that the need for implementation of Global One Health in low-resource
      settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec)
      Global Consortium launched the International Congress on Pathogens at the Human
      Animal Interface (ICOPHAI) in order to address important challenges and needs for
      capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the
      second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to
      share and discuss issues related to zoonotic infectious diseases worldwide. In
      addition to strong scientific reports in eight thematic areas that necessitate
      One Health implementation, the congress identified four key capacity-building
      needs: (1) development of adequate science-based risk management policies, (2)
      skilled-personnel capacity building, (3) accredited veterinary and public health
      diagnostic laboratories with a shared database, and (4) improved use of existing
      natural resources and implementation. The aim of this review is to highlight
      advances in key zoonotic disease areas and the One Health capacity needs. 

PMID- 25393304
TI  - Predictive value of interferon-lambda gene polymorphisms for treatment response
      in chronic hepatitis C.
AB  - BACKGROUND: IL28B gene polymorphism is the best baseline predictor of response to
      interferon alfa-based antiviral therapies in chronic hepatitis C. Recently, a new
      IFN-L4 polymorphism was identified as first potential functional variant for
      induction of IL28B expression. Individualization of interferon alfa-based
      therapies based on a combination of IL28B/IFN-L4 polymorphisms may help to
      optimize virologic outcome and economic resources. METHODS: Optimization of
      treatment outcome prediction was assessed by combination of different IL28B and
      IFN-L4 polymorphisms in patients with chronic HCV genotype 1 (n = 385), 2/3 (n =
      267), and 4 (n = 220) infection treated with pegylated interferon alfa (PEG-IFN)
      and ribavirin with (n = 79) or without telaprevir. Healthy people from Germany (n
      = 283) and Egypt (n = 96) served as controls. RESULTS: Frequencies of beneficial
      IL28B rs12979860 C/C genotypes were lower in HCV genotype 1/4 infected patients
      in comparison to controls (20-35% vs. 46-47%) this was also true for ss469415590
      TT/TT (20-35% vs. 45-47%). Single interferon-lambda SNPs (rs12979860, rs8099917,
      ss469415590) correlated with sustained virologic response (SVR) in genotype 1, 3,
      and 4 infected patients while no association was observed for genotype 2.
      Interestingly, in genotype 3 infected patients, best SVR prediction was based on
      IFN-L4 genotype. Prediction of SVR with high accuracy (71-96%) was possible in
      genotype 1, 2, 3 and 4 infected patients who received PEG-IFN/ribavirin
      combination therapy by selection of beneficial IL28B rs12979860 C/C and/or
      ss469415590 TT/TT genotypes (p<0.001). For triple therapy with first generation
      protease inhibitors (PIs) (boceprevir, telaprevir) prediction of high SVR (90%)
      rates was based on the presence of at least one beneficial genotype of the 3 IFN
      lambda SNPs. CONCLUSION: IFN-L4 seems to be the best single predictor of SVR in
      genotype 3 infected patients. For optimized prediction of SVR by treatment with
      dual combination or first generation PI triple therapies, grouping of interferon
      lambda haplotypes may be helpful with positive predictive values of 71-96%.

PMID- 25393305
TI  - Risk prediction of emergency department revisit 30 days post discharge: a
      prospective study.
AB  - BACKGROUND: Among patients who are discharged from the Emergency Department (ED),
      about 3% return within 30 days. Revisits can be related to the nature of the
      disease, medical errors, and/or inadequate diagnoses and treatment during their
      initial ED visit. Identification of high-risk patient population can help device
      new strategies for improved ED care with reduced ED utilization. METHODS AND
      FINDINGS: A decision tree based model with discriminant Electronic Medical Record
      (EMR) features was developed and validated, estimating patient ED 30 day revisit
      risk. A retrospective cohort of 293,461 ED encounters from HealthInfoNet (HIN),
      Maine's Health Information Exchange (HIE), between January 1, 2012 and December
      31, 2012, was assembled with the associated patients' demographic information and
      one-year clinical histories before the discharge date as the inputs. To validate,
      a prospective cohort of 193,886 encounters between January 1, 2013 and June 30,
      2013 was constructed. The c-statistics for the retrospective and prospective
      predictions were 0.710 and 0.704 respectively. Clinical resource utilization,
      including ED use, was analyzed as a function of the ED risk score. Cluster
      analysis of high-risk patients identified discrete sub-populations with
      distinctive demographic, clinical and resource utilization patterns. CONCLUSIONS:
      Our ED 30-day revisit model was prospectively validated on the Maine State HIN
      secure statewide data system. Future integration of our ED predictive analytics
      into the ED care work flow may lead to increased opportunities for targeted care
      intervention to reduce ED resource burden and overall healthcare expense, and
      improve outcomes.

PMID- 25393306
TI  - Epigallocatechin-3-gallate attenuates impairment of learning and memory in
      chronic unpredictable mild stress-treated rats by restoring hippocampal
      autophagic flux.
AB  - Epigallocatechin gallate (EGCG) is a major polyphenol in green tea with
      beneficial effects on the impairment in learning and memory. Autophagy is a
      cellular process that protects neurons from stressful conditions. The present
      study was designed to investigate whether EGCG can rescue chronic unpredictable
      mild stress (CUMS)-induced cognitive impairment in rats and whether its
      protective effect involves improvement of autophagic flux. As expected, our
      results showed that CUMS significantly impaired memory performance and inhibited
      autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the
      same time, we observed an increased neuronal loss and activated mammalian target
      of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6k) signaling in the CA1
      regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p.)
      significantly improved those behavioral alterations, attenuated histopathological
      abnormalities in hippocampal CA1 regions, reduced amyloid beta1-42 (Abeta1-42)
      levels, and restored autophagic flux. However, blocking autophagic flux with
      chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG.
      Taken together, these findings suggest that the impaired autophagy in CA1 regions
      of CUMS rats may contribute to learning and memory impairment. Therefore, we
      conclude that EGCG attenuation of CUMS-induced learning and memory impairment may
      be through rescuing autophagic flux. 

PMID- 25393307
TI  - Distinct strains of Toxoplasma gondii feature divergent transcriptomes regardless
      of developmental stage.
AB  - Using high through-put RNA sequencing, we assayed the transcriptomes of three
      different strains of Toxoplasma gondii representing three common genotypes under
      both in vitro tachyzoite and in vitro bradyzoite-inducing alkaline stress culture
      conditions. Strikingly, the differences in transcriptional profiles between the
      strains, RH, PLK, and CTG, is much greater than differences between tachyzoites
      and alkaline stressed in vitro bradyzoites. With an FDR of 10%, we identified 241
      genes differentially expressed between CTG tachyzoites and in vitro bradyzoites,
      including 5 putative AP2 transcription factors. We also observed a close
      association between cell cycle regulated genes and differentiation. By Gene Set
      Enrichment Analysis (GSEA), there are a number of KEGG pathways associated with
      the in vitro bradyzoite transcriptomes of PLK and CTG, including pyrimidine
      metabolism and DNA replication. These functions are likely associated with cell
      cycle arrest. When comparing mRNA levels between strains, we identified 1,526
      genes that were differentially expressed regardless of culture-condition as well
      as 846 differentially expressed only in bradyzoites and 542 differentially
      expressed only in tachyzoites between at least two strains. Using GSEA, we
      identified that ribosomal proteins were expressed at significantly higher levels
      in the CTG strain than in either the RH or PLK strains. This association holds
      true regardless of life cycle stage. 

PMID- 25393308
TI  - Inferring viral dynamics in chronically HCV infected patients from the spatial
      distribution of infected hepatocytes.
AB  - Chronic liver infection by hepatitis C virus (HCV) is a major public health
      concern. Despite partly successful treatment options, several aspects of
      intrahepatic HCV infection dynamics are still poorly understood, including the
      preferred mode of viral propagation, as well as the proportion of infected
      hepatocytes. Answers to these questions have important implications for the
      development of therapeutic interventions. In this study, we present methods to
      analyze the spatial distribution of infected hepatocytes obtained by single cell
      laser capture microdissection from liver biopsy samples of patients chronically
      infected with HCV. By characterizing the internal structure of clusters of
      infected cells, we are able to evaluate hypotheses about intrahepatic infection
      dynamics. We found that individual clusters on biopsy samples range in size from
      4-50 infected cells. In addition, the HCV RNA content in a cluster declines from
      the cell that presumably founded the cluster to cells at the maximal cluster
      extension. These observations support the idea that HCV infection in the liver is
      seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the
      amount of intracellular HCV RNA is a proxy for how long a cell has been infected,
      we estimate based on models of intracellular HCV RNA replication and accumulation
      that cells in clusters have been infected on average for less than a week.
      Further, we do not find a relationship between the cluster size and the estimated
      cluster expansion time. Our method represents a novel approach to make inferences
      about infection dynamics in solid tissues from static spatial data.

PMID- 25393309
TI  - BDC12-4.1 T-cell receptor transgenic insulin-specific CD4 T cells are resistant
      to in vitro differentiation into functional Foxp3+ T regulatory cells.
AB  - The infusion of ex vivo-expanded autologous T regulatory (Treg) cells is
      potentially an effective immunotherapeutic strategy against graft-versus-host
      disease (GvHD) and several autoimmune diseases, such as type 1 diabetes (T1D).
      However, in vitro differentiation of antigen-specific T cells into functional and
      stable Treg (iTreg) cells has proved challenging. As insulin is the major
      autoantigen leading to T1D, we tested the capacity of insulin-specific T-cell
      receptor (TCR) transgenic CD4(+) T cells of the BDC12-4.1 clone to convert into
      Foxp3(+) iTreg cells. We found that in vitro polarization toward Foxp3(+) iTreg
      was effective with a majority (>70%) of expanded cells expressing Foxp3. However,
      adoptive transfer of Foxp3(+) BDC12-4.1 cells did not prevent diabetes onset in
      immunocompetent NOD mice. Thus, in vitro polarization of insulin-specific BDC12
      4.1 TCR transgenic CD4(+) T cells toward Foxp3+ cells did not provide dominant
      tolerance in recipient mice. These results highlight the disconnect between an in
      vitro acquired Foxp3(+) cell phenotype and its associated in vivo regulatory
      potential.

PMID- 25393310
TI  - A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast
      cancer.
AB  - INTRODUCTION: Triple-negative breast cancer (TNBC) is a heterogeneous disease
      with no definitive prognostic markers. As a major component of tight junctions,
      claudins (CLDNs) presumably play an important role in carcinogenesis and
      progression of breast cancer. This study was aimed at determining the
      relationship between the expression of CLDNs and the clinical outcomes of TNBCs.
      MATERIALS AND METHODS: The surgical specimens of primary breast tumors from a
      consecutive cohort of 173 TNBC patients were retrospectively collected. The
      membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by
      immunohistochemistry. Then, the associations between CLDN expression,
      clinicopathological features, and clinical outcomes were assessed. RESULTS:
      Positive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in
      44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of
      CLDN1 expression was related to only lymph node metastasis (P = 0.014). The rate
      of CLDN4-positive tumors was significantly increased in tumors of a higher grade
      (P = 0.003). Importantly, negative CLDN1 expression was associated with worse
      relapse-free survival (RFS) in both lymph node positive (LN+) and negative (LN-)
      cases (both P<0.001). Similarly it was also associated with shorter overall
      survival (OS)(P = 0.003 in LN+ cases; P = 0.018 in LN- cases). In the LN+
      subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P =
      0.008). Multivariate analysis revealed that negative CLDN1 expression was an
      independent prognostic factor for high risk of both recurrence and death (HR
      5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P = 0.002).
      However, neither CLDN4 nor CLDN7 expression was associated with survival.
      CONCLUSION: In TNBC, the CLDN1-negative phenotype predicts a high risk of
      recurrence and death. The absence of CLDN1 expression is strongly suggested to be
      an independent adverse prognostic factor in this heterogeneous subtype of breast
      cancer.

PMID- 25393312
TI  - Utilization of surveillance after polypectomy in the medicare population--a
      cohort study.
AB  - BACKGROUND: Surveillance in patients with previous polypectomy was underused in
      the Medicare population in 1994. This study investigates whether expansion of
      Medicare reimbursement for colonoscopy screening in high-risk individuals has
      reduced the inappropriate use of surveillance. METHODS: We used Kaplan-Meier
      analysis to estimate time to surveillance and polyp recurrence rates for Medicare
      beneficiaries with a colonoscopy with polypectomy between 1998 and 2003 who were
      followed through 2008 for receipt of surveillance colonoscopy. Generalized
      Estimating Equations were used to estimate risk factors for: 1) failing to
      undergo surveillance and 2) polyp recurrence among these individuals. Analyses
      were stratified into three 2-year cohorts based on baseline colonoscopy date.
      RESULTS: Medicare beneficiaries undergoing a colonoscopy with polypectomy in the
      1998-1999 (n = 4,136), 2000-2001 (n = 3,538) and 2002-2003 (n = 4,655) cohorts
      had respective probabilities of 30%, 26% and 20% (p<0.001) of subsequent
      surveillance events within 3 years. At the same time, 58%, 52% and 45% (p<0.001)
      of beneficiaries received a surveillance event within 5 years. Polyp recurrence
      rates after 5 years were 36%, 30% and 26% (p<0.001) respectively. Older age (>=
      70 years), female gender, later cohort (2000-2001 & 2002-2003), and severe
      comorbidity were the most important risk factors for failure to undergo a
      surveillance event. Male gender and early cohort (1998-1999) were the most
      important risk factors for polyp recurrence. CONCLUSIONS: Expansion of Medicare
      reimbursement for colonoscopy screening in high-risk individuals has not reduced
      underutilization of surveillance in the Medicare population. It is important to
      take action now to improve this situation, because polyp recurrence is
      substantial in this population.

PMID- 25393311
TI  - Methadone induction in primary care for opioid dependence: a pragmatic randomized
      trial (ANRS Methaville).
AB  - OBJECTIVE: Methadone coverage is poor in many countries due in part to methadone
      induction being possible only in specialized care (SC). This multicenter
      pragmatic trial compared the effectiveness of methadone treatment between two
      induction models: primary care (PC) and SC. METHODS: In this study, registered at
      ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone
      treatment for at least one month or receiving buprenorphine but needing to switch
      were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10
      sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary
      outcome was self-reported abstinence from street-opioids at 12 months (M12) (with
      an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were
      abstinence during follow-up, engagement in treatment (i.e. completing the
      induction period), retention and satisfaction with the explanations provided by
      the physician. Primary analysis used intention to treat (ITT). Mixed models and
      the log-rank test were used to assess the arm effect (PC vs. SC) on the course of
      abstinence and retention, respectively. RESULTS: In the ITT analysis (n = 155 in
      PC, 66 in SC), which compared the proportions of street-opioid abstinent
      participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as
      street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis
      showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and
      satisfaction with the explanations provided by the physician were significantly
      higher in PC than SC. Retention in methadone and abstinence during follow-up were
      comparable in both arms (p = 0.47, p = 0.39, respectively). CONCLUSIONS: Under
      appropriate conditions, methadone induction in primary care is feasible and
      acceptable to both physicians and patients. It is as effective as induction in
      specialized care in reducing street-opioid use and ensuring engagement and
      retention in treatment for opioid dependence. TRIAL REGISTRATION: Number Eudract
      2008-001338-28; ClinicalTrials.gov: NCT00657397; International Standard
      Randomized Controlled Trial Number Register ISRCTN31125511.

PMID- 25393314
TI  - Quantitative analysis of somatosensory cortex development in metatherians and
      monotremes, with comparison to the laboratory rat.
AB  - Metatherians and monotremes are born in an immature state, followed by prolonged
      nurturing by maternal lactation. Quantitative analysis of isocortical sections
      held in the collections at the Museum fur Naturkunde, Berlin was used to compare
      the pace of somatosensory cortex development relative to body size and pallial
      thickness between metatherian groups, monotremes, and the laboratory rat.
      Analysis indicated that the pace of pallial growth in the monotremes is much
      lower than that in the metatherians or laboratory rat, with an estimated 8.6-fold
      increase in parietal cortex thickness between 10 and 100 mm body length, compared
      to a 10- to 20-fold increase among the metatherians and the rat. It was found
      that aggregation of cortical plate neurons occurs at similar embryo size in the
      mammals studied (around 8-14 mm body length) and a similar pallial thickness
      (around 200 um), but that proliferative zone involution occurs at a much higher
      body size and pallial thickness in the monotremes compared to the metatherians
      and the laboratory rat. The observations suggest that cortical development in the
      monotremes is slower and subject to different regulatory signals to the therians
      studied. The slow pace may be related to either generally slower metabolism in
      monotremes or less efficient nutrient supply to the offspring due to the lack of
      teats.

PMID- 25393313
TI  - Functional diversity of carbohydrate-active enzymes enabling a bacterium to
      ferment plant biomass.
AB  - Microbial metabolism of plant polysaccharides is an important part of
      environmental carbon cycling, human nutrition, and industrial processes based on
      cellulosic bioconversion. Here we demonstrate a broadly applicable method to
      analyze how microbes catabolize plant polysaccharides that integrates
      carbohydrate-active enzyme (CAZyme) assays, RNA sequencing (RNA-seq), and
      anaerobic growth screening. We apply this method to study how the bacterium
      Clostridium phytofermentans ferments plant biomass components including glucans,
      mannans, xylans, galactans, pectins, and arabinans. These polysaccharides are
      fermented with variable efficiencies, and diauxies prioritize metabolism of
      preferred substrates. Strand-specific RNA-seq reveals how this bacterium responds
      to polysaccharides by up-regulating specific groups of CAZymes, transporters, and
      enzymes to metabolize the constituent sugars. Fifty-six up-regulated CAZymes were
      purified, and their activities show most polysaccharides are degraded by multiple
      enzymes, often from the same family, but with divergent rates, specificities, and
      cellular localizations. CAZymes were then tested in combination to identify
      synergies between enzymes acting on the same substrate with different catalytic
      mechanisms. We discuss how these results advance our understanding of how
      microbes degrade and metabolize plant biomass.

PMID- 25393315
TI  - Subtyping based on readiness and confidence: the identification of help-seeking
      profiles for gamblers accessing web-based counselling.
AB  - BACKGROUND AND AIMS: Problem gamblers are not a homogeneous group and recent data
      suggest that subtyping can improve treatment outcomes. This study administered
      three readiness rulers and aimed to identify subtypes of gamblers accessing a
      national web-based counselling service based on these rulers. METHODS:
      Participants were 1204 gamblers (99.4% problem gamblers) who accessed a single
      session of web-based counselling in Australia. Measures included three readiness
      rulers (importance, readiness and confidence to resist an urge to gamble),
      demographics and the Problem Gambling Severity Index (PGSI). RESULTS: Gamblers
      reported high importance of change [mean = 9.2, standard deviation (SD) = 1.51]
      and readiness to change (mean = 8.86, SD = 1.84), but lower confidence to resist
      an urge to gamble (mean = 3.93, SD = 2.44) compared with importance and
      readiness. The statistical fit indices of a latent class analysis identified a
      four-class model. Subtype 1 was characterized by a very high readiness to change
      and very low confidence to resist an urge to gamble (n = 662, 55.0%) and subtype
      2 reported high readiness and low confidence (n = 358, 29.7%). Subtype 3 reported
      moderate ratings on all three rulers (n = 139, 11.6%) and subtype 4 reported high
      importance of change but low readiness and confidence (n = 45, 3.7%). A
      multinomial logistic regression indicated that subtypes differed by gender (P <
      0.001), age (P = 0.01), gambling activity (P < 0.05), preferred mode of gambling
      (P < 0.001) and PGSI score (P < 0.001). CONCLUSIONS: Problem gamblers in
      Australia who seek web-based counselling comprise four distinct subgroups based
      on self-reported levels of readiness to change, confidence to resist the urge to
      gamble and importance of change.

PMID- 25393316
TI  - Platelets interact with Coxsackieviruses B and have a critical role in the
      pathogenesis of virus-induced myocarditis.
AB  - BACKGROUND: To further understand the role of platelets in the pathogenesis of
      viral infections we explored platelet interaction with Coxsackieviruses B (CVB) 1
      and 3. CVB is a group of viruses that cause the majority of human enterovirus
      related viral myocarditis; their receptor (CAR) is expressed on the platelet
      surface and there is a well-characterized CVB3-induced myocarditis murine model.
      METHODS: Human platelets were infected with CVB1 and 3 and viruses were detected
      in pellets and in supernatants. C57BL/6J mice with or without platelet depletion
      were inoculated with CVB3 and peripheral blood and heart samples collected at
      different times post-infection. RESULTS: CVB1 and 3 RNA and a capsid protein were
      detected in infected platelets. Despite the fact that titration assays in Vero
      cells showed increasing infectivity titers over time, supernatants and pellets
      from infected platelets showed similar levels, suggesting that platelets were not
      susceptible to a replicative infectivity cycle. CVB binding was CAR-independent
      and resulted in P-selectin and phosphatidylserine (PS) exposure. CVB3-infected
      mice showed a rapid thrombocytopenia that correlated with an increase in platelet
      PS exposure and platelet-leukocyte aggregates without modification of platelet P
      selectin expression or von Willebrand factor levels. Mortality, viremia, heart
      viral titers and myocarditis were significantly higher in platelet-depleted than
      normal animals. Type I IFN levels were not changed but IgG levels were lower in
      infected and platelet-depleted mice. CONCLUSIONS: Our data reveal that platelets
      play a critical role in host survival and immune response against CVB3 infection.

PMID- 25393317
TI  - Mammalian Non-CpG Methylation: Stem Cells and Beyond.
AB  - Although CpG dinucleotides remain the primary site for DNA methylation in
      mammals, there is emerging evidence that DNA methylation at non-CpG sites (CpA,
      CpT and CpC) is not only present in mammalian cells, but may play a unique role
      in the regulation of gene expression. For some time it has been known that non
      CpG methylation is abundant in plants and present in mammalian embryonic stem
      cells, but non-CpG methylation was thought to be lost upon cell differentiation.
      However, recent publications have described a role for non-CpG methylation in
      adult mammalian somatic cells including the adult mammalian brain, skeletal
      muscle, and hematopoietic cells and new interest in this field has been
      stimulated by the availability of high throughput sequencing techniques that can
      accurately measure this epigenetic modification. Genome wide assays indicate that
      non-CpG methylation is negligible in human fetal brain, but abundant in human
      adult brain tissue. Genome wide measurement of non-CpG methylation coupled with
      RNA-Sequencing indicates that in the human adult brain non-CpG methylation levels
      are inversely proportional to the abundance of mRNA transcript at the associated
      gene. Additionally specific examples where alterations in non-CpG methylation
      lead to changes in gene expression have been described; in PGC1alpha in human
      skeletal muscle, IFN-gamma in human T-cells and SYT11 in human brain, all of
      which contribute to the development of human disease. 

PMID- 25393319
TI  - Controlled dehydration of a ruthenium complex-DNA crystal induces reversible DNA
      kinking.
AB  - Hydration-dependent DNA deformation has been known since Rosalind Franklin
      recognized that the relative humidity of the sample had to be maintained to
      observe a single conformation in DNA fiber diffraction. We now report for the
      first time the crystal structure, at the atomic level, of a dehydrated form of a
      DNA duplex and demonstrate the reversible interconversion to the hydrated form at
      room temperature. This system, containing d(TCGGCGCCGA) in the presence of Lambda
      [Ru(TAP)2(dppz)](2+) (TAP = 1,4,5,8-tetraazaphenanthrene, dppz = dipyrido[3,2
      a:2',3'-c]phenazine), undergoes a partial transition from an A/B hybrid to the A
      DNA conformation, at 84-79% relative humidity. This is accompanied by an increase
      in kink at the central step from 22 degrees  to 51 degrees , with a large
      movement of the terminal bases forming the intercalation site. This transition is
      reversible on rehydration. Seven data sets, collected from one crystal at room
      temperature, show the consequences of dehydration at near-atomic resolution. This
      result highlights that crystals, traditionally thought of as static systems, are
      still dynamic and therefore can be the subject of further experimentation. 

PMID- 25393318
TI  - Role of the MPTP in conditioning the heart - translatability and mechanism.
AB  - Mitochondria have long been known to be the gatekeepers of cell fate. This is
      particularly so in the response to acute ischaemia-reperfusion injury (IRI).
      Following an acute episode of sustained myocardial ischaemia, the opening of the
      mitochondrial permeability transition pore (MPTP) in the first few minutes of
      reperfusion, mediates cell death. Preventing MPTP opening at the onset of
      reperfusion using either pharmacological inhibitors [such as cyclosporin A (CsA)
      ] or genetic ablation has been reported to reduce myocardial infarct (MI) size in
      animal models of acute IRI. Interestingly, the endogenous cardioprotective
      intervention of ischaemic conditioning, in which the heart is protected against
      MI by applying cycles of brief ischaemia and reperfusion to either the heart
      itself or a remote organ or tissue, appears to be mediated through the inhibition
      of MPTP opening at reperfusion. Small proof-of-concept clinical studies have
      demonstrated the translatability of this therapeutic approach to target MPTP
      opening using CsA in clinical settings of acute myocardial IRI. However, given
      that CsA is a not a specific MPTP inhibitor, more novel and specific inhibitors
      of the MPTP need to be discovered - the molecular identification of the MPTP
      should facilitate this. In this paper, we review the role of the MPTP as a target
      for cardioprotection, the potential mechanisms underlying MPTP inhibition in the
      setting of ischaemic conditioning, and the translatability of MPTP inhibition as
      a therapeutic approach in the clinical setting.

PMID- 25393320
TI  - Rational classification of portal vein thrombosis and its clinical significance.
AB  - Portal vein thrombosis (PVT) is commonly classified into acute (symptom duration
      <60 days and absence of portal carvernoma and portal hypertension) and chronic
      types. However, the rationality of this classification has received little
      attention. In this study, 60 patients (40 men and 20 women) with PVT were
      examined using contrast-enhanced computed tomography (CT). The percentage of vein
      occlusion, including portal vein (PV) and superior mesenteric vein (SMV), was
      measured on CT image. Of 60 patients, 17 (28.3%) met the criterion of acute PVT.
      Symptoms occurred more frequently in patients with superior mesenteric vein
      thrombosis (SMVT) compared to those without SMVT (p<0.001). However, there was no
      significant difference in PV occlusion between patients with and without
      symptoms. The frequency of cavernous transformation was significantly higher in
      patients with complete PVT than those with partial PVT (p<0.001). Complications
      of portal hypertension were significantly associated with cirrhosis (p<0.001)
      rather than with the severity of PVT and presence of cavernoma. These results
      suggest that the severity of PVT is only associated with the formation of portal
      cavernoma but unrelated to the onset of symptoms and the development of portal
      hypertension. We classified PVT into complete and partial types, and each was
      subclassified into with and without portal cavernoma. In conclusion, neither
      symptom duration nor cavernous transformation can clearly distinguish between
      acute and chronic PVT. The new classification system can determine the
      pathological alterations of PVT, patency of portal vein and outcome of treatment
      in a longitudinal study. 

PMID- 25393321
TI  - Production and characterization of bioactive metabolites from piezotolerant deep
      sea fungus Nigrospora sp. in submerged fermentation.
AB  - AIMS: To produce and characterize bioactive metabolites from piezotolerant marine
      fungus Nigrospora sp. in submerged fermentation. METHODS AND RESULTS: A distinct
      marine strain, Nigrospora sp. NIOT has been isolated from a depth of 800 m at the
      Arabian Sea. The 18S rRNA and internal transcribed spacers (ITS) analysis
      demonstrates its close association with the genus Nigrospora. Effect of pH,
      temperature, salinity, carbon source and amino acids was studied to optimize the
      fermentation conditions. Optimal mycelia growth and secondary metabolites
      production were observed at 6.0-8.0 pH, 20-30 degrees C temperature, 7.5%
      salinity, sucrose as carbon source and tryptophan as amino acid source. The
      extracellular secondary metabolites exhibited high antimicrobial activities
      against both gram-positive and gram-negative pathogenic bacteria with minimal
      inhibitory concentration (MIC) values higher than 30 MUg ml(-1). Strongest
      cytotoxicity was observed in all cell lines tested, GI50 (growth inhibition by
      50%) was calculated to be 1.35, 3.2, 0.13 and 0.35 MUg ml(-1) against U937, MCF
      7, A673 and Jurkat, respectively. Fourier transform infrared spectroscopy (FTIR)
      and gas chromatography-mass spectrometry (GC-MS) analyses of secondary
      metabolites confirmed the production of antimicrobial and anticancer substances.
      CONCLUSIONS: A piezotolerant fungus Nigrospora sp. NIOT isolated from deep sea
      environment was successfully cultured under submerged fermentation. The secondary
      metabolites produced from this organism showed potent antimicrobial and
      anticancer activities with immediate application to cosmetics and pharmaceutical
      industries. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study
      exploring Nigrospora sp. from 800 m in marine environment. This deep sea fungus
      under optimized culture conditions effectively produced bioactive secondary
      metabolites such as griseofulvin, spirobenzofuran and pyrone derivatives at
      higher concentrations.

PMID- 25393322
TI  - Spherical nucleic acid nanoparticle conjugates enhance G-quadruplex formation and
      increase serum protein interactions.
AB  - To understand the effect of three-dimensional oligonucleotide structure on
      protein corona formation, we studied the identity and quantity of human serum
      proteins that bind to spherical nucleic acid (SNA) nanoparticle conjugates. SNAs
      exhibit cellular uptake properties that are remarkably different from those of
      linear nucleic acids, which have been related to their interaction with certain
      classes of proteins. Through a proteomic analysis, this work shows that the
      protein binding properties of SNAs are sequence-specific and supports the
      conclusion that the oligonucleotide tertiary structure can significantly alter
      the chemical composition of the SNA protein corona. This knowledge will impact
      our understanding of how nucleic acid-based nanostructures, and SNAs in
      particular, function in complex biological milieu. 

PMID- 25393323
TI  - High-intensity warm-ups: effects during subsequent intermittent exercise.
AB  - High-intensity, short-duration warm-up techniques improve acute physical
      performance, but sparse research has examined their consequence when followed by
      intermittent activity, which is pertinent to team sports. The authors compared a
      5-repetitionmaximum (5RM) leg-press, a small-sided game (SSG), and a current team
      sport warm-up in 10 semiprofessional soccer players after 2 intermittent-activity
      protocols consisting of 15 repetitions of a 60-s circuit that included sprinting,
      slalom, walking, jogging, decelerations, changes of direction, backward running,
      and striding activities. There was a large improvement in countermovement-jump
      height in the 5RM after the 1st intermittent-activity protocol (mean, +/-90% CL
      6.0, +/-4.0%, P=.03) and a small improvement after the 2nd (4.6, +/-4.0%, P=.04)
      compared with team sport. Reactive agility was moderately faster via 5RM after
      the 1st intermittent-activity protocol (3.1, +/-2.6%: P=.04) and the 2nd (5.7, +/
      2.7%, P=.001) than via SSG. There was a small improvement in reactive agility
      after the 1st intermittent-activity protocol in the 5RM, compared with team sport
      (3.3, +/-2.9%, P=.04). There was a small improvement in mean 20-m-sprint times
      after both intermittent-activity protocols in the 5RM, compared with SSG (4.2, +/
      2.0%, P=.01, and 4.3, +/-2.0%, P=.01) and, after the 1st intermittent-activity
      protocol only, compared with team sport (4.2, +/-2.1%, P=0.02). Small increases
      in blood lactate concentration were observed (46.7, +/-18.6%, P=.01) in the 5RM
      compared with the SSG after the 2nd intermittent-activity protocol. Improved
      performances after the 5RM warm-up should encourage practitioners to reduce
      activity time and include high-intensity tasks in team-sport warmups aimed at
      inducing a potentiating effect.

PMID- 25393324
TI  - Solid-state NMR as an effective method of polymorphic analysis: solid dosage
      forms of clopidogrel hydrogensulfate.
AB  - Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling
      drugs in the world. In this paper, we have described a rapid and convenient
      method of verification which polymorph of HSCL is present in its final solid
      dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio
      gauge-including projector-augmented wave calculations of NMR shielding constants
      is appropriate for currently available commercial solid dosage forms of HSCL.
      Furthermore, such structural characterization can assist with the development of
      new pharmaceutical products containing HSCL and also be useful in the
      identification of counterfeit drugs.

PMID- 25393325
TI  - Fracturesis Jointitis: Causes, Symptoms, and Treatment in Groundwater
      Communities.
AB  - Fracturesis Jointitis is a grammatical disorder characterized by failure or
      inability to understand the difference between overarching and specific terms of
      brittle deformation features. The disorder leads to the use of the word
      "fracture" as a specific type of discontinuity rather than as an overarching term
      for mechanical breaks in rocks. This condition appears to be prevalent among
      groundwater practitioners working with fractured rocks. Common signs and symptoms
      of Fracturesis Jointitis include the use of terms such as "joints and fractures"
      and "joints, faults and fractures" when describing fractures in rocks. At best,
      such terms imply that a "fracture" is one of many kinds of features like joints
      and faults, and at worst that joints and faults are not fractures but something
      else. Using proper terms to identify specific fracture types is critical because
      fractures may act as either barriers to groundwater flow (e.g., faults or
      deformation bands) or conduits for flow (e.g., faults and joints), The treatment
      for Fracturesis Jointitis involves an education campaign highlighting to the
      groundwater community the different fracture types that exist, the modes by which
      fractures propagate and the role that these fractures play in facilitating or
      hindering groundwater flow. Those afflicted by Fracturesis Jointitis can be cured
      of the condition by avoiding the word "fractures" in phrases such as "joints and
      fractures" or by adding descriptive words before the word "fractures" to specify
      fracture types (e.g., "foliation-parallel" fractures). Only with a concerted
      education campaign can we rid our community of Fracturesis Jointitis. 

PMID- 25393326
TI  - Pentaplex PCR as screening assay for jellyfish species identification in food
      products.
AB  - Salted jellyfish, a traditional food in Asian Countries, is nowadays spreading on
      the Western markets. In this work, we developed a Pentaplex PCR for the
      identification of five edible species (Nemopilema nomurai, Rhopilema esculentum,
      Rhizostoma pulmo, Pelagia noctiluca, and Cotylorhiza tuberculata), which cannot
      be identified by a mere visual inspection in jellyfish products sold as food. A
      common degenerated forward primer and five specie-specific reverse primers were
      designed to amplify COI gene regions of different lengths. Another primer pair
      targeted the 28SrRNA gene and was intended as common positive reaction control.
      Considering the high level of degradation in the DNA extracted from acidified and
      salted products, the maximum length of the amplicons was set at 200 bp. The PCR
      was developed using 66 reference DNA samples. It gave successful amplifications
      in 85.4% of 48 ready to eat products (REs) and in 60% of 30 classical salted
      products (CPs) collected on the market. 

PMID- 25393328
TI  - CXCL12/CXCR4 chemokine signaling in spinal glia induces pain hypersensitivity
      through MAPKs-mediated neuroinflammation in bone cancer rats.
AB  - The activation of MAPK pathways in spinal cord and subsequent production of
      proinflammatory cytokines in glial cells contribute to the development of spinal
      central sensitization, the basic mechanism underlying bone cancer pain (BCP). Our
      previous study showed that spinal CXCL12 from astrocytes mediates BCP generation
      by binding to CXCR4 in both astrocyters and microglia. Here, we verified that
      CXCL12/CXCR4 signaling contributed to BCP through a MAPK-mediated mechanism. In
      naive rats, a single intrathecal administration of CXCL12 considerably induced
      pain hyperalgesia and phosphorylation expression of spinal MAPK members
      (including extracellular signal-regulated kinase, p38, and c-Jun N-terminal
      kinase), which could be partially prevented by pre-treatment with CXCR4 inhibitor
      AMD3100. This CXCL12-induced hyperalgesia was also reduced by MAPK inhibitors. In
      bone cancer rats, tumor cell inoculation into the tibial cavity caused prominent
      and persistent pain hyperalgesia, and associated with up-regulation of CXCL12 and
      CXCR4, activation of glial cells, phosphorylation of MAPKs, and production of
      proinflammatory cytokines in the spinal cord. These tumor cell inoculation
      induced behavioral and neurochemical alterations were all suppressed by blocking
      CXCL12/CXCR4 signaling or MAPK pathways. Taken together, these results
      demonstrate that spinal MAPK pathways mediated CXCL12/CXCR4-induced pain
      hypersensitivity in bone cancer rats, which could be druggable targets for
      alleviating BCP and glia-derived neuroinflammation. Following tumor cell
      inoculation, chemokine CXCL12 from astrocytes spreads around the spinal
      environment, resulting in functional activation of CXCR4-expressing astrocytes
      and microglia. Once glia are activated, they may initiate MAPK (mitogen-activated
      protein kinase) pathways, and subsequently produce proinflammatory cytokines and
      chemokines. Among them, CXCL12 could reinforce the astrocytic and microglial
      activation in autocrine and paracrine manners. Such positive feedback loops
      sustain perseverant neuroinflammation, facilitate glial activation, and finally
      lead to bone cancer pain. IL = interleukin; TNF = tumor necrosis factor.

PMID- 25393329
TI  - Inflammatory pseudotumours of the oesophagus--histological and
      immunohistochemical findings.
AB  - AIMS: Inflammatory oesophageal pseudotumours are rare lesions, thought to be
      reactive. Due to marked atypia of the stromal cells, these can be misdiagnosed as
      malignancies. The objective of this study was to characterize histological and
      immunohistochemical features of a series of inflammatory pseudotumours of the
      oesophagus. METHODS AND RESULTS: We present 12 cases of inflammatory oesophageal
      pseudotumours, occurring in seven females and five males, with a mean age of 57.3
      years. Clinical presentations were variable; dysphagia, abdominal pain and weight
      loss and upper gastrointestinal bleed. In a majority of the cases, nodules or
      masses in the distal oesophagus were identified at endoscopy. Microscopically,
      the lamina propria in all 12 cases contained inflammation and granulation tissue.
      Ten of 12 cases showed mucosal ulceration and 11 of 12 cases had acutely inflamed
      epithelium. Markedly atypical pleomorphic stromal cells with prominent nucleoli
      were identified in all 12 cases. Immunohistochemistry showed uniform positivity
      for vimentin in 11 of 11 cases, and two of seven cases demonstrated weak focal
      positivity for smooth muscle actin. The cells were negative for all other
      markers. CONCLUSIONS: Reactive oesophageal lesions can show marked nuclear atypia
      in stromal fibroblasts/myofibroblasts, which are easily mistaken for
      malignancies. Pathologists must consider the diagnosis of an inflammatory
      pseudotumour if stromal atypia is present in an inflammatory background.

PMID- 25393330
TI  - Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Cav 2.2
      Blocker Multitarget Ligands.
AB  - N-type voltage-dependent Ca(2+) channels (CaV 2.2) are located at nerve endings
      in the central and peripheral nervous systems and are strongly associated with
      the pathological processes of cerebral ischaemia and neuropathic pain. CaV 2.2
      blockers such as the omega-conotoxin MVIIA (Prialt) are analgesic and have opioid
      sparing effects. With the aim to develop new multitarget analgesic compounds, we
      designed the first omega-conotoxin/opioid peptidomimetics based on the enkephalin
      like sequence Tyr-D-Ala-Gly-Phe (for the opioid portion) and two fragments
      derived from the loop-2 pharmacophore of omega-conotoxin MVIIA. Antinociceptive
      activity evaluated in vitro and in vivo revealed differential affinity for CaV
      2.2 and opioid receptors and no significant synergistic activity. 

PMID- 25393333
TI  - Safety of flexible bronchoscopy, rigid bronchoscopy, and endobronchial ultrasound
      guided transbronchial needle aspiration in patients with malignant space
      occupying brain lesions.
AB  - BACKGROUND: Bronchoscopy in patients with space-occupying brain lesions is
      anecdotally felt to carry a high risk of neurologic complications. METHODS: We
      conducted a retrospective cohort study of patients with evidence of a malignant,
      space-occupying brain lesion who were referred for flexible or rigid bronchoscopy
      or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).
      The primary outcome of interest was the incidence of neurologic complications
      following the procedures in these patients. RESULTS: Of the 103 enrolled
      patients, flexible bronchoscopy was performed in 41, rigid bronchoscopy in 12,
      and EBUS-TBNA in 50. Among these patients, 41 (40%) had evidence suggestive of
      increased intracranial pressure on imaging. Among all study patients, none (95%
      CI, 0-0.035) had neurologic, procedure-specific, or sedation-specific
      complications, and the level of care was not escalated in any of these patients.
      CONCLUSIONS: On the basis of our findings, we recommend that procedures such as
      flexible or rigid bronchoscopy or EBUS-TBNA in patients with malignant space
      occupying brain lesions should be considered reasonably safe as long as
      neurologic findings are stable.

PMID- 25393334
TI  - Critical experimental evaluation of key methods to detect, size and quantify
      nanoparticulate silver.
AB  - Different analytical techniques, sedimentation flow field fractionation (SdFFF),
      asymmetrical flow field flow fractionation (AF4), centrifugal liquid
      sedimentation (CLS) and dynamic light scattering (DLS) have been used to give
      complementary size information about suspensions of silver nanoparticles (AgNPs)
      in the size range of 20-100 nm by taking advantage of the different physical
      principles on which are based. Particle morphology was controlled by TEM
      (Transmission Electron Microscopy). Both SdFFF and AF4 were able to accurately
      size all AgNPs; among sedimentation based techniques, CLS underestimated the
      average sizes of larger samples (70 and 100 nm), but it produced the best
      separation of bimodal mixtures Ag40/60 and Ag40/70 mix compared to SdFFF. On the
      contrary, DLS overestimated the average sizes of the smallest samples (20 and 30
      nm) and it was unable to deal with bimodal mixtures. Quantitative mass and number
      particle size distributions were also calculated starting from UV-vis signals and
      ICP-MS data and the results evaluated as a means to address the issue of
      determining nanoparticle size distributions as required for implementation of
      European regulations relating to labeling of nanomaterials in consumer products.
      The results are discussed in light of possible particle aggregation state,
      analysis repeatability, size resolution and quantitative recoveries. 

PMID- 25393336
TI  - Physiological, Perceptual and Psychological Responses of Career versus Volunteer
      Firefighters to Live-fire Training Drills.
AB  - A primary objective of the present study was to examine the effect of short-term
      live-fire firefighting activities on key physiological, perceptual and
      psychological variables and whether occupational status influenced these
      responses. It was also of interest to examine whether individual difference
      factors differentiated the occupational status groups and if so, whether such
      individual difference factors influenced perceptual and psychological responses
      to firefighting activities. Male firefighters (n = 52 career, n = 53 volunteer
      firefighters) participated in 18 min of simulated firefighting activity in a
      training structure that contained live fires. Measures of heart rate (HR) and
      Tcore were obtained before and after firefighting activities along with
      perceptions of thermal sensations, exertion, respiratory distress and affect.
      Firefighting activities resulted in significant elevations in HR and Tcore ,
      whereas thermal sensations, respiratory distress, exertion and affect all showed
      significant and sizable changes reflecting greater distress and dysphoria.
      Occupational status and individual difference factors accounted for some of this
      negative change. The findings replicate and extend previous work by demonstrating
      the influence of occupational status and individual difference factors in the
      psychological responses to firefighting activity. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 25393331
TI  - The association between acute respiratory distress syndrome, delirium, and in
      hospital mortality in intensive care unit patients.
AB  - RATIONALE: Both acute respiratory distress syndrome (ARDS) and intensive care
      unit (ICU) delirium are associated with significant morbidity and mortality.
      However, the risk of delirium and its impact on mortality in ARDS patients is
      unknown. OBJECTIVES: To determine if ARDS is associated with a higher risk for
      delirium compared with respiratory failure without ARDS, and to determine the
      association between ARDS and in-hospital mortality after adjusting for delirium.
      METHODS: Prospective observational cohort study of adult ICU patients admitted to
      two urban academic hospitals. MEASUREMENTS AND MAIN RESULTS: Delirium was
      assessed daily using the Confusion Assessment Method for the ICU and Richmond
      Agitation and Sedation Scale. Of the 564 patients in our cohort, 48 had ARDS
      (9%). Intubated patients with ARDS had the highest prevalence of delirium
      compared with intubated patients without ARDS and nonintubated patients (73% vs.
      52% vs. 21%, respectively; P < 0.001). After adjusting for common risk factors
      for delirium, ARDS was associated with a higher risk for delirium compared with
      mechanical ventilation without ARDS (odds ratio [OR], 6.55 [1.56-27.54]; P = 0.01
      vs. OR, 1.98 [1.16-3.40]; P < 0.013); reference was nonintubated patients.
      Although ARDS was significantly associated with hospital mortality (OR, 10.44
      [3.16-34.50]), the effect was largely reduced after adjusting for delirium and
      persistent coma (OR, 5.63 [1.55-20.45]). CONCLUSIONS: Our findings suggest that
      ARDS is associated with a greater risk for ICU delirium than mechanical
      ventilation alone, and that the association between ARDS and in-hospital
      mortality is weakened after adjusting for delirium and coma. Future studies are
      needed to determine if prevention and reduction of delirium in ARDS patients can
      improve outcomes.

PMID- 25393337
TI  - The clinical anatomy of the right ventricle.
AB  - Because the systemic and pulmonary circulations are arranged in series, the right
      and left ventricles of the human heart have similar stroke volumes (with only
      minute beat-to-beat changes). Besides propelling the same volume of blood through
      the corresponding circulations, the two ventricles also share common structures
      such as the pericardium, the interventricular septum and the coronary arteries
      and veins-all of which complete the dynamic and integrated picture of the human
      heart. However, there are marked differences between the left and right
      ventricles as each is adapted to separate and dissimilar vascular beds, including
      particular reactivity to stress, hormones, and drugs. Of the two, the right
      ventricle (RV) has so far been either more difficult to approach from the
      diagnostic point of view or even overlooked, while the left ventricle (LV) has
      been considered the main pump, and diagnostic and therapeutic measures have been
      considered to apply equally to the LV and RV. This review article presents an
      update, portraying the RV from the clinical anatomical point of view, and
      endeavors to underscore the main particulars of the RV with clinical and surgical
      applications.

PMID- 25393338
TI  - A systematic review of diastolic stress tests in heart failure with preserved
      ejection fraction, with proposals from the EU-FP7 MEDIA study group.
AB  - AIMS: Cardiac function should be assessed during stress in patients with
      suspected heart failure with preserved ejection fraction (HFPEF), but it is
      unclear how to define impaired diastolic reserve. METHODS AND RESULTS: We
      conducted a systematic review to identify which pathophysiological changes serve
      as appropriate targets for diagnostic imaging. We identified 38 studies of 1111
      patients with HFPEF (mean age 65 years), 744 control patients without HFPEF, and
      458 healthy subjects. Qualifying EF was >45-55%; diastolic dysfunction at rest
      was a required criterion in 45% of studies. The initial workload during bicycle
      exercise (25 studies) varied from 12.5 to 30 W (mean 23.1 +/- 4.6), with
      increments of 10-25 W (mean 19.9 +/- 6) and stage duration 1-5 min (mean 2.5 +/-
      1); targets were submaximal (n = 8) or maximal (n = 17). Other protocols used
      treadmill exercise, handgrip, dobutamine, lower body negative pressure,
      nitroprusside, fluid challenge, leg raising, or atrial pacing. Reproducibility of
      echocardiographic variables during stress and validation against independent
      reference criteria were assessed in few studies. Change in E/e' was the most
      frequent measurement, but there is insufficient evidence to establish this or
      other tests for routine use when evaluating patients with HFPEF. CONCLUSIONS: To
      meet the clinical requirements of performing stress testing in elderly subjects,
      we propose a ramped exercise protocol on a semi-supine bicycle, starting at 15 W,
      with increments of 5 W/min to a submaximal target (heart rate 100-110 b.p.m., or
      symptoms). Measurements during submaximal and recovery stages should include
      changes from baseline in LV long-axis function and indirect echocardiographic
      indices of LV diastolic pressure.

PMID- 25393339
TI  - Novel Clinical Scale for Evaluating Pre-Operative Risk of Cerebral Herniation
      from Traumatic Epidural Hematoma.
AB  - Secondary massive cerebral infarction (MCI) is the predominant prognostic factor
      for cerebral herniation from epidural hematoma (EDH) and determines the need for
      decompressive craniectomy. In this study, we tested the clinical feasibility and
      reliability of a novel pre-operative risk scoring system, the EDH-MCI scale, to
      guide surgical decision making. It is comprised of six risk factors, including
      hematoma location and volume, duration and extent of cerebral herniation, Glasgow
      Coma Scale score, and presence of preoperative shock, with a total score ranging
      from 0 to 18 points. Application of the EDH-MCI scale to guide surgical
      modalities for initial hematoma evacuation surgery for 65 patients (prospective
      cohort, 2012.02-2014.01) showed a significant improvement in the accuracy of the
      selected modality (95.38% vs. 77.95%; p = 0.002) relative to the results for an
      independent set of 126 patients (retrospective cohort, 2007.01-2012.01) for whom
      surgical modalities were decided empirically. Results suggested that simple
      hematoma evacuation craniotomy was sufficient for patients with low risk scores
      (<=9 points), whereas decompressive craniectomy in combination with duraplasty
      were necessary only for those with high risk scores (>=13 points). In patients
      with borderline risk scores (10-12 points), those having unstable vital signs,
      coexistence of severe secondary brainstem injury, and unresponsive dilated pupils
      after emergent burr hole hematoma drainage had a significantly increased
      incidence of post-traumatic MCI and necessity of radical surgical treatments. In
      conclusion, the novel pre-operative risk EDH-MCI evaluation scale has a
      satisfactory predictive and discriminative performance for patients who are at
      risk for the development of secondary MCI and therefore require decompressive
      craniectomy.

PMID- 25393340
TI  - Rapid and cost-efficient enumeration of rare cancer cells from whole blood by low
      loss centrifugo-magnetophoretic purification under stopped-flow conditions.
AB  - We present a substantially improved design and functionality of a centrifugo
      magnetophoretic platform which integrates direct immunoseparation and cost
      efficient, bright-field detection of cancer cells in whole blood. All liquid
      handling takes place in a disposable cartridge with geometry akin to a
      conventional compact disc (CD). The instrumentation required to process such a
      "lab-on-a-disc" cartridge can be as simple and cost-efficient as the rotor on a
      common optical disc drive. In a first step, target cells in a blood sample are
      specifically bound to paramagnetic microbeads. The sample is then placed into the
      disc cartridge and spun. In the second step, magnetically tagged target cells are
      separated by a co-rotating, essentially lateral magnetic field from the
      background population of abundant blood cells, and also from unbound magnetic
      beads. A stream of target cells centrifugally sediments through a stagnant liquid
      phase into a designated detection chamber. The continuous, multiforce
      immunoseparation proceeds very gently, i.e. the mechanical and hydrodynamic
      stress to the target cells is minimized to mitigate the risk of cell loss by
      collective entrapment in the background cells or vigorous snapping against a
      wall. We successfully demonstrate the extraction of MCF7 cancer cells at
      concentrations as low as 1 target cell per MUl from a background of whole blood,
      with capture efficiencies of up to 88%. Its short time-to-answer is a notable
      characteristic of this system, with 10% of target cells collected in the first
      minute after their loading to the system and the remainder captured within the
      following 10 min. All the above-mentioned factors synergetically combine to
      leverage the development of a prospective point-of-care device for CTC detection.

PMID- 25393341
TI  - Retreatment and outcomes of recurrent intracranial vertebral artery dissecting
      aneurysms after stent assisted coiling: a single center experience.
AB  - BACKGROUND AND PURPOSE: The retreatment of recurrent intracranial vertebral
      artery dissecting aneurysms (VADAs) after stent assisted coiling (SAC) has not
      yet been studied. The purpose of this study was to evaluate the strategies and
      outcomes for retreatment of recurrent VADAs after SAC. METHODS: Between September
      2009 and November 2013, six consecutive patients presenting with recurrent
      intracranial VADAs after SAC were enrolled in this study. They were all male with
      age ranging from 29 to 54 years (mean age, 46.2 years). The procedures of
      treatments and angiographic and clinical follow-up were reviewed retrospectively.
      Retreatment modalities were selected individually according to the
      characteristics of recurrence. The outcomes of retreatment were evaluated by
      angiographic and clinical follow-up. RESULTS: Six patients with recurrent
      intracranial VADAs after SAC were retreated, with second SAC in three patients,
      coil embolization, double overlapping stents placement and endovascular occlusion
      with aneurysm trapping in one patient, respectively. Immediate angiographic
      outcomes of retreatment were: complete occlusion in three patients, nearly
      complete occlusion in two patients, and contrast medium retention in dissecting
      aneurysm in one patient. All cases were technically successful. No complications
      related to endovascular procedures occurred. Angiographic follow-up was available
      in all five patients treated with second SAC or double overlapping stents, which
      was complete occlusion in four patients, obliteration of parent artery in one
      patient, showing no recurrence at 4-11 months (mean: 8.6 months). Clinical follow
      up was performed in all six patients at 11-51 months after initial endovascular
      treatment and at 9-43 months after retreatment. The mRS of last clinical follow
      up was excellent in five patients and mild disability in only one patient.
      CONCLUSIONS: Endovascular retreatment is feasible and effective for recurrent
      intracranial VADAs after SAC. Individualized strategies of retreatment should be
      enacted according to the characteristics and reasons for the recurrence.

PMID- 25393342
TI  - Differential signaling by regulatory subunits of phosphoinositide-3-kinase
      influences cell survival in INS-1E insulinoma cells.
AB  - Class 1A phosphoinositide 3-kinase (PI3K) is essential for beta-cell growth and
      survival. Although PI3K has been studied extensively in diabetes the effect of
      alternatively spliced isoforms of the catalytic subunit p85alpha on beta cell
      proliferation and survival remains to be defined.We examined expression and
      signaling of alternatively spliced PI3K regulatory subunits p85alpha, p55alpha
      and p50alpha in insulinoma cells (INS-1E), an insulin-producing beta cell line.
      PI3K regulatory isoforms were knocked down by siRNA transfection or overexpressed
      by adenoviral gene delivery.Knockdown of p85alpha elevated PI3K activation
      determined by Akt phosphorylation at baseline and after stimulation with growth
      factors. In contrast, Akt phosphorylation was inhibited by overexpression of all
      isoforms of p85alpha. Correspondingly, p55alpha and p85alpha overexpression
      decreased downstream kinase GSK-3 phosphorylation as well, whereas p50alpha
      overexpression resulted in an activation of GSK-3. Moreover, overexpression of
      p50alpha and p85alpha lead to retinoblastoma protein hyperphosphorylation and S
      phase entry. Upon challenge of INS-1E cells with a cytotoxic cytokine cocktail,
      levels of p85alpha were reduced and p50alpha was upregulated. Selective
      overexpression of p50alpha prevented cytokine induced apoptosis in INS-1E
      cells.In conclusion, signalling of p50alpha, p55alpha and p85alpha is similar at
      the level of Akt, but differentially influence downstream GSK-3 activation and
      cell cycle entry. PI3K isoform p50alpha induction by cytokines provides a link
      between regeneration and cell survival under cytotoxic stress in insulin
      producing pancreatic beta-cells. 

PMID- 25393343
TI  - Type 2 Diabetes Mellitus Non-genetic Rhesus Monkey Model Induced by High Fat and
      High Sucrose Diet.

PMID- 25393344
TI  - Preserving whole blood in formalin extends the specimen stability period for
      manual cell counts for fish.
AB  - BACKGROUND: Total blood cell counts for fish are challenging, especially due to
      cell fragility. Thrombocyte aggregation, cell distortion, and lysis can occur
      within hours of collection; therefore, hemocytometer counts may not be possible
      for large sample numbers. Preserving whole blood in formalin offers a simple way
      to extend the specimen stability period for cell counts. OBJECTIVES: The
      objectives of this study were to characterize and compare the analytical
      performance of the Natt-Herrick method for fish blood cell counts using freshly
      collected and formalin-fixed specimens. METHODS: Specimens from 11 elasmobranch
      species (n = 36) were compared for WBC counts. WBC, RBC, and thrombocyte counts
      from 50 striped bass, Morone saxatilis, were compared including 2 time points for
      the formalin-preserved cells (appr. 1-week and 1-month storage). Coefficient of
      variation (CV), bias, and total error (TEcalc ) were calculated. TEcalc was
      compared with allowable total error (TEa ) defined by the Clinical Laboratory
      Improvements Amendment (CLIA) for human blood cell counts. RESULTS: The CV and
      TEcalc for fresh and fixed WBC and thrombocyte counts met CLIA limits. In both
      the fresh and preserved cells, the RBC CV and TEcalc were nearly 3 times higher
      than the TEa . CONCLUSIONS: Preserving freshly collected blood in 10% formalin is
      a reliable method to maintain cell morphology for manual counts for up to 1 month
      post collection. This is especially useful for field studies, where laboratory
      access is limited. Further evaluation is needed to determine the clinical
      usefulness of the manual RBC count in fish.

PMID- 25393345
TI  - Polycyclic aromatic hydrocarbon exposure in household air pollution from solid
      fuel combustion among the female population of Xuanwei and Fuyuan counties,
      China.
AB  - Exposure to polycyclic aromatic hydrocarbons (PAHs) from burning "smoky"
      (bituminous) coal has been implicated as a cause of the high lung cancer
      incidence in the counties of Xuanwei and Fuyuan, China. Little is known about
      variations in PAH exposure from throughout the region nor how fuel source and
      stove design affects exposure. Indoor and personal PAH exposure resulting from
      solid fuel combustion in Xuanwei and Fuyuan was investigated using repeated 24 h
      particle bound and gas-phase PAH measurements, which were collected from 163
      female residents of Xuanwei and Fuyuan. 549 particle bound (283 indoor and 266
      personal) and 193 gas phase (all personal) PAH measurements were collected. Mixed
      effect models indicated that PAH exposure was up to 6 times higher when burning
      smoky coal than smokeless coal and varied by up to a factor of 3 between
      different smoky coal geographic sources. PAH measurements from unventilated
      firepits were up to 5 times that of ventilated stoves. Exposure also varied
      between different room sizes and season of measurement. These findings indicate
      that PAH exposure is modulated by a variety of factors, including fuel type, coal
      source, and stove design. These findings may provide valuable insight into
      potential causes of lung cancer in the area. 

PMID- 25393346
TI  - An Acoustic-Based Method to Detect and Quantify the Effect of Exhalation into a
      Dry Powder Inhaler.
AB  - BACKGROUND: Dry powder inhaler (DPI) users frequently exhale into their inhaler
      mouthpiece before the inhalation step. This error in technique compromises the
      integrity of the drug and results in poor bronchodilation. This study
      investigated the effect of four exhalation factors (exhalation flow rate,
      distance from mouth to inhaler, exhalation duration, and relative air humidity)
      on dry powder dose delivery. Given that acoustic energy can be related to the
      factors associated with exhalation sounds, we then aimed to develop a method of
      identifying and quantifying this critical inhaler technique error using acoustic
      based methods. METHODS: An in vitro test rig was developed to simulate this
      critical error. The effect of the four factors on subsequent drug delivery were
      investigated using multivariate regression models. In a further study we then
      used an acoustic monitoring device to unobtrusively record the sounds 22
      asthmatic patients made whilst using a Diskus(TM) DPI. Acoustic energy was
      employed to automatically detect and analyze exhalation events in the audio
      files. RESULTS: All exhalation factors had a statistically significant effect on
      drug delivery (p<0.05); distance from the inhaler mouthpiece had the largest
      effect size. Humid air exhalations were found to reduce the fine particle
      fraction (FPF) compared to dry air. In a dataset of 110 audio files from 22
      asthmatic patients, the acoustic method detected exhalations with an accuracy of
      89.1%. We were able to classify exhalations occurring 5 cm or less in the
      direction of the inhaler mouthpiece or recording device with a sensitivity of
      72.2% and specificity of 85.7%. CONCLUSIONS: Exhaling into a DPI has a
      significant detrimental effect. Acoustic based methods can be employed to
      objectively detect and analyze exhalations during inhaler use, thus providing a
      method of remotely monitoring inhaler technique and providing personalized
      inhaler technique feedback.

PMID- 25393347
TI  - Novel stacked double purse-string closure.

PMID- 25393348
TI  - The risorius muscle: anatomic considerations with reference to botulinum
      neurotoxin injection for masseteric hypertrophy.
AB  - BACKGROUND: The botulinum neurotoxin Type A (BTX) injection into the masseter
      muscle often causes a change in the facial expression. There is as yet no precise
      anatomic evidence to support this etiologic factor of constrained facial
      expressions. OBJECTIVE: The aim of this study was to clarify the location and
      boundaries of the risorius muscle and its topographical relationship with the
      surrounding structures. MATERIALS AND METHODS: This study involved the dissection
      of 48 hemifaces. The locations of origin and insertion points of the risorius
      muscle were measured, and the masseter muscle was divided into 6 equally sized
      rectangular areas. RESULTS: Cases where the masseter muscle was covered by the
      risorius muscle were classified into the following 4 types: in Type A, Area III
      was partially covered by the risorius (17.8%); in Type B, Area VI was partially
      covered (20.0%); in Type C, Areas III and VI were partially covered (53.3%); and
      in Type D, Areas II, III, and VI were covered (6.7%). CONCLUSION: These findings
      suggest that the medial part of the masseter muscle represents a hazard zone into
      which the injection of BTX may affect the risorius muscle, potentially resulting
      in iatrogenic unnatural facial expressions.

PMID- 25393349
TI  - Surgical smoke in dermatologic surgery.
AB  - BACKGROUND: Potential dangers associated with smoke generated during
      electrosurgery have been described. However, the use of smoke management in
      dermatology is unknown. There is no objective data showing the amount or the
      composition of the smoke generated in dermatologic surgeries. OBJECTIVE: To
      assess the use of smoke management in dermatologic surgery and provide data on
      the amount and chemical composition of surgical smoke. METHODS: A total of 997
      surveys were sent to dermatologic surgeons across the United States to assess the
      use of smoke management. Amounts and concentrations of particulates and chemical
      composition were measured during electrosurgery using a particulate meter and the
      Environmental Protection Agency-standardized gas chromatography-mass spectrometry
      analysis. RESULTS: Thirty-two percent of the surgeons responded to the survey,
      and 77% of the respondents indicated no use of smoke management at all. Only
      approximately 10% of surgeons reported consistent use of smoke management. Active
      electrosurgery produced significant amounts of particulates. In addition,
      surgical smoke contained high concentrations of known carcinogens, such as
      benzene, butadiene, and acetonitrile. CONCLUSION: Surgical smoke contains toxic
      compounds and particulates. Most dermatologic surgeons do not use smoke
      management within their practices. Raising the awareness of the potential risks
      can help increase the use of smoke management.

PMID- 25393350
TI  - Trends of keratinocyte carcinoma mortality rates in the United States as reported
      on death certificates, 1999 through 2010.
AB  - BACKGROUND: From 1969 to 1998, keratinocyte carcinoma (KC) mortality rates
      declined as reported on death certificates, despite increasing incidence of KC.
      OBJECTIVE: To estimate KC mortality trends from 1999 to 2010 in the United
      States. METHODS: Descriptive and linear regression analysis using population
      based death certificate data from the US National Center for Health Statistics.
      RESULTS: On average, 1,491 deaths from nongenital KC and 1,058 deaths from
      genital KC were reported annually. Keratinocyte carcinoma mortality rates were
      stable or increasing over the study period. Highest nongenital mortality rates
      were seen in those older than 85 years (p < .001), men (p < .001), whites (p <
      .001), the South for white males (p = .001) and white females (p = .018), and
      nonmetropolitan areas for white males (p <.001), white females (p < .001), and
      black females (p = .005). Correlation between state UV Index and KC mortality
      existed for men (p = .004) but not for women (p = .379). Genital KC deaths
      increased with age (p < .001), in women (p < .001), and in less urbanized areas
      for white males (p < .001). CONCLUSION: Keratinocyte carcinoma poses a serious
      health burden, which may be underestimated by death certificate reporting.
      Mortality rates are no longer declining. Increasing awareness of genital and
      nongenital KC, especially the elderly, and population-based studies with
      controlled reporting of KC mortality are needed.

PMID- 25393351
TI  - A reference (all-in-one) image demonstrating the outcome of suction blister
      formation in vitiligo surgery.

PMID- 25393352
TI  - Free margin distortion with fusiform closures: the apical angle relationship.

PMID- 25393354
TI  - Unique basaloid findings during Mohs surgery for basal cell carcinoma: a
      dermatopathology challenge.

PMID- 25393353
TI  - A prospective study of pain control by a 2-step irradiance schedule during
      topical photodynamic therapy of nonmelanoma skin cancer.
AB  - BACKGROUND: Topical photodynamic therapy (PDT) for selected nonmelanoma skin
      cancer using 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has
      yielded high long-term complete response rates with very good cosmesis. Pain
      during light activation of the photosensitizer can be a serious adverse event. A
      2-step irradiance protocol has previously been shown to minimize ALA-PDT pain.
      OBJECTIVE: To determine the irradiance-dependent pain threshold for MAL-PDT, to
      adapt the 2-step protocol to a light-emitting diode (LED) light source, and
      assess clinical response. METHODS: In this prospective study, 25 superficial
      basal cell carcinoma (sBCC) received an initial irradiance by laser at 40 or 50
      mW/cm2, or LED at 35 mW/cm2 followed by an irradiance at 70 mW/cm2 for a total of
      75 J/cm2. Pain levels were recorded for both irradiance steps. Efficacy was
      assessed at 6, 12, or 24 months. RESULTS: Pain was mild in the 40/70 mW/cm2 laser
      cohort. Three instances of irradiance-limiting pain occurred at 50/70 mW/cm2.
      Pain was minimal in the 35/70 mW/cm2 LED cohort. Clinical response rates were 80%
      in the 50/70 mW/cm2 laser cohort and 90% in the 35/70 mW/cm2 LED cohort.
      CONCLUSION: Topical PDT can be effectively delivered to sBCC with minimal
      treatment-related pain by a 2-step irradiance protocol.

PMID- 25393355
TI  - Repigmentation of vitiligo using the follicular unit extraction technique.

PMID- 25393356
TI  - Efficient charge separation in Li(+) @C60 supramolecular complexes with electron
      donors.
AB  - Lithium-ion-encapsulated fullerene (Li(+) @C60 ) exhibits greatly enhanced
      reactivity in photoinduced electron-transfer reduction with electron donors
      compared with pristine C60 . The enhanced reactivity of Li(+) @C60 results from
      the more positive one-electron reduction potential of Li(+) @C60 (+0.14 V versus
      a standard calomel electrode (SCE)) than that of C60 (-0.43 V versus SCE),
      whereas the reorganization energy of electron transfer of Li(+) @C60 (1.01 eV)
      becomes larger than that of C60 (0.73 eV) because of the change in electrostatic
      interactions of encapsulated Li(+) upon electron transfer. Li(+) @C60 can form
      strong supramolecular complexes with various anionic electron donors through
      electrostatic interactions. Li(+) @C60 can also form strong supramolecular pi
      complexes with various electron donors, such as cyclic porphyrin dimers,
      corannulene, and crown ether fused monopyrrolotetrathiafulvalenes. Photoinduced
      electron transfer from electron donors to Li(+) @C60 afforded long-lived charge
      separated states of supramolecular complexes between electron donors and Li(+)
      @C60 . A photoelectrochemical solar cell composed of supramolecular nanoclusters
      of Li(+) @C60 and zinc sulfonated meso-tetraphenylporphyrin exhibits significant
      enhancement in the photoelectrochemical performance than that of the reference
      system containing only a single component.

PMID- 25393358
TI  - Which is the preferred modality of renal access for a trainee urologist:
      ultrasonography or fluoroscopy? Results of a prospective randomized trial.
AB  - BACKGROUND AND PURPOSE: In percutaneous nephrolithotomy (PCNL), placement of the
      access tract into the kidney is an important aspect of the procedure and is
      responsible for the steep learning curve associated with the operation. The aim
      of the current prospective randomized trial was to assess the duration of
      radiation exposure along with the safety and efficacy of PCNL done by a trainee,
      utilizing either ultrasonography (US) or fluoroscopic guidance to obtain access.
      PATIENTS AND METHODS: Sixty-four patients with <=3 cm renal calculi undergoing
      single-tract PCNL by trainee urologists (experience of <25 PCNL's) were
      randomized into US- and fluoroscopic-guided access groups (32 in each). In Group
      1 (US guided), puncture was done using a 3.5/5 MHz US probe with a puncture
      attachment, whereas the triangulation technique with biplanar C-arm fluoroscopy
      was utilized in group 2 (fluoroscopic guided). Patient demographics, stone
      parameters, intraoperative characteristics, fluoroscopy durations, and
      postoperative outcomes were analyzed. RESULTS: Both groups were comparable as far
      as patient and stone characteristics were concerned. The fluoroscopy exposure
      during the puncture phase (T2) and overall (T) was significantly lower in the US
      group at 9.0+/-20.8 vs 43.8+/-34.8, (p<0.0001) and 204.3+/-84 vs 239.9+/-77.5,
      (p=0.04). Six patients in group1 required fluoroscopic adjustment (p=0.03). All
      other intra- and postoperative parameters were similar in both the groups.
      CONCLUSION: Both ultrasound and fluoroscopic guidance for renal access are
      equally safe and feasible in the hands of a trainee urologist. Total fluoroscopy
      duration and exposure time during puncture were both significantly less in the
      ultrasound group. Expertise in fluoroscopic-guided access is essential for a
      novice to effectively achieve access in all possible situations.

PMID- 25393357
TI  - Three-dimensional co-culture of C2C12/PC12 cells improves skeletal muscle tissue
      formation and function.
AB  - Engineered muscle tissues demonstrate properties far from native muscle tissue.
      Therefore, fabrication of muscle tissues with enhanced functionalities is
      required to enable their use in various applications. To improve the formation of
      mature muscle tissues with higher functionalities, we co-cultured C2C12 myoblasts
      and PC12 neural cells. While alignment of the myoblasts was obtained by culturing
      the cells in micropatterned methacrylated gelatin (GelMA) hydrogels, we studied
      the effects of the neural cells (PC12) on the formation and maturation of muscle
      tissues. Myoblasts cultured in the presence of neural cells showed improved
      differentiation, with enhanced myotube formation. Myotube alignment, length and
      coverage area were increased. In addition, the mRNA expression of muscle
      differentiation markers (Myf-5, myogenin, Mefc2, MLP), muscle maturation markers
      (MHC-IId/x, MHC-IIa, MHC-IIb, MHC-pn, alpha-actinin, sarcomeric actinin) and the
      neuromuscular markers (AChE, AChR-epsilon) were also upregulated. All these
      observations were amplified after further muscle tissue maturation under
      electrical stimulation. Our data suggest a synergistic effect on the C2C12
      differentiation induced by PC12 cells, which could be useful for creating
      improved muscle tissue. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 25393359
TI  - Awareness and Interest in the West Virginia Health Insurance Marketplace.
AB  - The objective of this study is to examine the level of awareness of and interest
      in the Health Insurance Marketplace in West Virginia. Primary survey data were
      collected in July/August 2013 from a stratified sampling of West Virginians. A
      mailed survey was completed by respondents in a cross-sectional study. Key
      variables included general awareness of the Health Insurance Marketplace and the
      availability of subsidies, the individual mandate, interest in using the
      Marketplace, and perceptions of respondents' ability to qualify for financial
      assistance. A total of 6000 surveys were mailed containing a 9-page
      questionnaire; 1198 completed surveys were returned. Two months prior to launch,
      awareness of the Health Insurance Marketplace was low in West Virginia, yet
      interest in the Marketplace was higher among those most likely to benefit--the
      uninsured and residents likely to qualify for financial subsidies. West
      Virginians reported being familiar with the individual mandate. Efforts should be
      increased among government and nongovernment organizations at the federal, state,
      and local levels to heighten awareness of the Health Insurance Marketplace in
      West Virginia and, particularly, the availability of subsidies. Many, once made
      aware, expressed interest in learning more.

PMID- 25393360
TI  - Risks of vaginal breech delivery at term compared with elective cesarean section 
      reply to comments by Walker and Powell, and Sholapurkar.

PMID- 25393361
TI  - Capacity building in obstetrics and gynaecology through academic partnerships to
      improve global women's health beyond 2015.

PMID- 25393362
TI  - Does Physician Dispensing Increase Drug Expenditures? Empirical Evidence from
      Switzerland.
AB  - This paper analyzes whether the opportunity for physicians to dispense drugs
      increases healthcare expenditures. We study the case of Switzerland, where
      dispensing physicians face financial incentives to overprescribe and sell more
      expensive pharmaceuticals. Using comprehensive physician-level data, we exploit
      the regional variation in the dispensing regime to estimate causal effects. The
      empirical strategy consists of a doubly-robust estimation that combines inverse
      probability weighting with regression. Our main finding suggests that dispensing
      leads to higher drug costs on the order of 34% per patient.

PMID- 25393363
TI  - Comment on: The prognostic significance of tumour-stroma ratio in oestrogen
      receptor-positive breast cancer.

PMID- 25393364
TI  - Statin use and risk for ovarian cancer: a Danish nationwide case-control study.
AB  - BACKGROUND: Limited data suggest that statin use reduces the risk for ovarian
      cancer. METHODS: Using Danish nationwide registries, we identified 4103 cases of
      epithelial ovarian cancer during 2000-2011 and age-matched them to 58,706 risk
      set sampled controls. Conditional logistic regression was used to estimate
      adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for epithelial
      ovarian cancer overall, and for histological types, associated with statin use.
      RESULTS: We observed a neutral association between ever use of statins and
      epithelial ovarian cancer risk (OR=0.98, 95% CI=0.87-1.10), and no apparent risk
      variation according to duration, intensity or type of statin use. Decreased ORs
      associated with statin use were seen for mucinous ovarian cancer (ever statin
      use: OR=0.63, 95% CI=0.39-1.00). CONCLUSIONS: Statin use was not associated with
      overall risk for epithelial ovarian cancer. The inverse association between
      statin use and mucinous tumours merits further investigation.

PMID- 25393365
TI  - The BMP pathway either enhances or inhibits the Wnt pathway depending on the
      SMAD4 and p53 status in CRC.
AB  - BACKGROUND: Constitutive Wnt activation is essential for colorectal cancer (CRC)
      initiation but also underlies the cancer stem cell phenotype, metastasis and
      chemosensitivity. Importantly Wnt activity is still modulated as evidenced by
      higher Wnt activity at the invasive front of clonal tumours termed the beta
      catenin paradox. SMAD4 and p53 mutation status and the bone morphogenetic protein
      (BMP) pathway are known to affect Wnt activity. The combination of SMAD4 loss,
      p53 mutations and BMP signalling may integrate to influence Wnt signalling and
      explain the beta-catenin paradox. METHODS: We analysed the expression patterns of
      SMAD4, p53 and beta-catenin at the invasive front of CRCs using
      immunohistochemistry. We activated BMP signalling in CRC cells in vitro and
      measured BMP/Wnt activity using luciferase reporters. MTT assays were performed
      to study the effect of BMP signalling on CRC chemosensitivity. RESULTS: Eighty
      four percent of CRCs with high nuclear beta-catenin staining are SMAD4 negative
      and/or p53 aberrant. BMP signalling inhibits Wnt signalling in CRC only when p53
      and SMAD4 are unaffected. In the absence of SMAD4, BMP signalling activates Wnt
      signalling. When p53 is lost or mutated, BMP signalling no longer influences Wnt
      signalling. The cytotoxic effects of 5-FU are influenced in a similar manner.
      CONCLUSIONS: The BMP signalling pathway differentially modulates Wnt signalling
      dependent on the SMAD4 and p53 status. The use of BMPs in cancer therapy, as has
      been proposed by previous studies, should be targeted to individual cancers based
      on the mutational status of p53 and SMAD4.

PMID- 25393366
TI  - Physical function as a prognostic biomarker among cancer survivors.
AB  - BACKGROUND: We tested the hypothesis that objectively measured physical function
      predicts mortality among cancer survivors. METHODS: We assessed objectively
      measured physical function including the short physical performance battery
      (SPPB) and fast walk speed in older adult cancer survivors. RESULTS: Among 413
      cancer survivors, 315 (76%) died during a median follow-up of 11.0 years. In
      multivariable-adjusted analyses, each 1-unit increase in the SPPB score and 0.1 m
      s(-1) increase in fast walk speed predicted a 12% reduction in mortality (hazard
      ratio (HR): 0.88 (95% confidence interval (CI): 0.82-0.94); P<0.001, and HR: 0.88
      (95% CI: 0.82-0.96); P=0.003, respectively). CONCLUSIONS: Objectively measured
      physical function may predict mortality among cancer survivors.

PMID- 25393367
TI  - Histone deacetylase inhibitor SAHA epigenetically regulates miR-17-92 cluster and
      MCM7 to upregulate MICA expression in hepatoma.
AB  - BACKGROUND: Epigenetic therapy using histone deacetylase inhibitors (HDACi) has
      shown promise in clinical trials for the treatment of human malignancies. In
      addition to the immediate effects on the tumour cell growth, HDACi upregulates
      the expression of MHC class I-related chain molecules A and B (MICA and MICB),
      resulting in an enhanced susceptibility of tumour cells to natural killer cell
      mediated lysis. The molecular mechanism underlying is still unclear. METHODS: The
      transcriptional regulation mechanism underlying suberoylanilide hydroxamic acid
      (SAHA)-mediated regulation of MICA and related miRNA expression was investigated
      using promoter acetylation assays, bioinformatics analysis and chromatin
      immunoprecipitation assay. RESULTS: SAHA upregulates the transcription of MICA/B
      by promoting MICA-associated histone acetylation while suppressing the MICA/B
      targeting miRNAs miR-20a, miR-93 and miR-106b. The mechanism by which SAHA
      repressed miRNAs transcription involved repression of their host genes (miR-17-92
      cluster and MCM7). SAHA downregulated the miR-17-92 cluster by abolishing
      tyrosine phosphorylation of STAT3 and decreased MCM7 transcription through
      localised histone deacetylation. CONCLUSIONS: The HDACi SAHA epigenetically
      upregulates MICA expression through regulating the expression of miR-17-92
      cluster and MCM7 in hepatoma, thus enhancing the sensitivity of HCC to natural
      killer cell-mediated lysis. This novel mechanism of action provides promise for
      HDACi in therapy of HCC.

PMID- 25393368
TI  - A Phase I study of cyclin-dependent kinase inhibitor, AT7519, in patients with
      advanced cancer: NCIC Clinical Trials Group IND 177.
AB  - BACKGROUND: AT7519 is a small-molecular inhibitor of multiple cyclin-dependent
      kinases (CDKs). It shows encouraging anti-cancer activity against multiple cell
      lines and in tumour xenografts. This phase I study was conducted to evaluate the
      safety and tolerability of AT7519 given as 1-h intravenous infusion on days 1, 4,
      8 and 11 every 3 weeks. METHODS: Patients with advanced refractory solid tumours
      or non-Hodgkin's lymphoma were enroled. Dose escalation occurred in a 3+3 manner
      based on toxicity assessment. Pharmacokinetic samples were collected after first
      AT7519 infusion, whereas pharmacodynamics (PD) samples were obtained in selected
      patients. RESULTS: Thirty-four patients were enroled, and 32 received study
      treatments over 4 dose levels. Dose-limiting toxicities included mucositis,
      febrile neutropenia, rash, fatigue and hypokalemia. The recommended phase II dose
      (RP2D) was 27.0 mg m(-2). Ten of 19 patients evaluable for efficacy had stable
      disease as the best response (median duration: 3.3 months; range: 2.5 to 11.1
      months). There was no clinically significant QTc prolongation. There was an
      apparent dose proportional increase in AT7519 exposure. The PD studies showed
      reduction in markers of CDK activity in selected patients' skin biopsies post
      treatment. CONCLUSIONS: AT7519, when administered as an intravenous infusion on
      days 1, 4, 8 and 11, was well tolerated. The RP2D is 27.0 mg m(-2). At this dose
      level, plasma AT7519 concentrations were above the biologically active
      concentrations, and preliminary anti-cancer activity was observed in patients.
      This dosing schedule is being further evaluated in multiple phase II studies.

PMID- 25393369
TI  - Reponse to: comment on, 'Tumour-stroma ratio (TSR) in oestrogen-positive breast
      cancer patients'.

PMID- 25393371
TI  - Kinetic modelling of heterogeneous catalytic systems.
AB  - The importance of heterogeneous catalysis in modern life is evidenced by the fact
      that numerous products and technologies routinely used nowadays involve catalysts
      in their synthesis or function. The discovery of catalytic materials is, however,
      a non-trivial procedure, requiring tedious trial-and-error experimentation. First
      principles-based kinetic modelling methods have recently emerged as a promising
      way to understand catalytic function and aid in materials discovery. In
      particular, kinetic Monte Carlo (KMC) simulation is increasingly becoming more
      popular, as it can integrate several sources of complexity encountered in
      catalytic systems, and has already been used to successfully unravel the
      underlying physics of several systems of interest. After a short discussion of
      the different scales involved in catalysis, we summarize the theory behind KMC
      simulation, and present the latest KMC computational implementations in the
      field. Early achievements that transformed the way we think about catalysts are
      subsequently reviewed in connection to latest studies of realistic systems, in an
      attempt to highlight how the field has evolved over the last few decades. Present
      challenges and future directions and opportunities in computational catalysis are
      finally discussed. 

PMID- 25393370
TI  - MicroRNA expression profiling in male and female familial breast cancer.
AB  - BACKGROUND: Gender-associated epigenetic alterations are poorly investigated in
      male and female familial breast cancer (fBC). MicroRNAs may contribute to the
      different biology in men and women particularly related to RASSF1A pathways.
      METHODS: Microarray technology was used to evaluate miRNA profile in 24 male and
      43 female fBC. Key results were validated using RT-qPCR in an external samples
      set. In vitro studies were carried out to verify microRNA-target gene
      interaction. RESULTS: Pathway enrichment analysis with the 287 differentially
      expressed microRNAs revealed several signalling pathways differently regulated in
      male and female cases. Because we previously hypothesised a peculiar involvement
      of RASSF1A in male fBC pathogenesis, we focussed on the MAPK and the Hippo
      signalling pathways that are regulated by RASSF1A. Male miR-152 and miR-497
      upregulation and RASSF1A and NORE1A interacting gene downregulation were
      observed, confirming a possible indirect interaction between miRNAs and the two
      genes. CONCLUSIONS: For the first time, a different microRNA expression pattern
      in male and female fBC has been shown. Moreover, the importance of RASSF1A
      pathway in male fBC carcinogenesis has been confirmed, highlighting a possible
      role for miR-152 and miR-497 in controlling MAPK and Hippo signalling pathways,
      regulated by RASSF1A.

PMID- 25393373
TI  - Quantum mechanical molecular interactions for calculating the excitation energy
      in molecular environments: a first-order interacting space approach.
AB  - Intermolecular interactions regulate the molecular properties in proteins and
      solutions such as solvatochromic systems. Some of the interactions have to be
      described at an electronic-structure level. In this study, a commutator for
      calculating the excitation energy is used for deriving a first-order interacting
      space (FOIS) to describe the environmental response to solute excitation. The
      FOIS wave function for a solute-in-solvent cluster is solved by second-order
      perturbation theory. The contributions to the excitation energy are decomposed
      into each interaction and for each solvent. 

PMID- 25393372
TI  - Cyclooxygenase-2 silencing for the treatment of colitis: a combined in vivo
      strategy based on RNA interference and engineered Escherichia coli.
AB  - Nonpathogenic-invasive Escherichia coli (InvColi) bacteria are suitable for
      genetic transfer into mammalian cells and may act as a vehicle for RNA
      Interference (RNAi) in vivo. Cyclooxygenase-2 (COX-2) is overexpressed in
      ulcerative colitis (UC) and Crohn's disease (CD), two inflammatory conditions of
      the colon and small intestine grouped as inflammatory bowel disease (IBD). We
      engineered InvColi strains for anti-COX-2 RNAi (InvColi(shCOX2)), aiming to
      investigate the in vivo feasibility of a novel COX-2 silencing strategy in a
      murine model of colitis induced by dextran sulfate sodium (DSS). Enema
      administrations of InvColi(shCOX2) in DSS-treated mice led to COX-2
      downregulation, colonic mucosa preservation, reduced colitis disease activity
      index (DAI) and increased mice survival. Moreover, DSS/InvColi(shCOX2)-treated
      mice showed lower levels of circulating pro-inflammatory cytokines and a reduced
      colitis-associated shift of gut microbiota. Considering its effectiveness and
      safety, we propose our InvColi(shCOX2) strategy as a promising tool for molecular
      therapy in intestinal inflammatory diseases. 

PMID- 25393374
TI  - Responsive block copolymer photonics triggered by protein-polyelectrolyte
      coacervation.
AB  - Ionic interactions between proteins and polyelectrolytes are demonstrated as a
      method to trigger responsive transitions in block copolymer (BCP) photonic gels
      containing one neutral hydrophobic block and one cationic hydrophilic block.
      Poly(2-vinylpyridine) (P2VP) blocks in lamellar poly(styrene-b-2-vinylpyridine)
      block copolymer thin films are quaternized with primary bromides to yield swollen
      gels that show strong reflectivity peaks in the visible range; exposure to
      aqueous solutions of various proteins alters the swelling ratios of the
      quaternized P2VP (QP2VP) gel layers in the PS-QP2VP materials due to the ionic
      interactions between proteins and the polyelectrolyte. Parameters such as charge
      density, hydrophobicity, and cross-link density of the QP2VP gel layers as well
      as the charge and size of the proteins play significant roles on the photonic
      responses of the BCP gels. Differences in the size and pH-dependent charge of
      proteins provide a basis for fingerprinting proteins based on their temporal and
      equilibrium photonic response. The results demonstrate that the BCP gels and
      their photonic effect provide a robust and visually interpretable method to
      differentiate different proteins. 

PMID- 25393375
TI  - Thermostable artificial enzyme isolated by in vitro selection.
AB  - Artificial enzymes hold the potential to catalyze valuable reactions not observed
      in nature. One approach to build artificial enzymes introduces mutations into an
      existing protein scaffold to enable a new catalytic activity. This process
      commonly results in a simultaneous reduction of protein stability as an undesired
      side effect. While protein stability can be increased through techniques like
      directed evolution, care needs to be taken that added stability, conversely, does
      not sacrifice the desired activity of the enzyme. Ideally, enzymatic activity and
      protein stability are engineered simultaneously to ensure that stable enzymes
      with the desired catalytic properties are isolated. Here, we present the use of
      the in vitro selection technique mRNA display to isolate enzymes with improved
      stability and activity in a single step. Starting with a library of artificial
      RNA ligase enzymes that were previously isolated at ambient temperature and were
      therefore mostly mesophilic, we selected for thermostable active enzyme variants
      by performing the selection step at 65  degrees C. The most efficient enzyme,
      ligase 10 C, was not only active at 65  degrees C, but was also an order of
      magnitude more active at room temperature compared to related enzymes previously
      isolated at ambient temperature. Concurrently, the melting temperature of ligase
      10 C increased by 35 degrees compared to these related enzymes. While low
      stability and solubility of the previously selected enzymes prevented a
      structural characterization, the improved properties of the heat-stable ligase 10
      C finally allowed us to solve the three-dimensional structure by NMR. This
      artificial enzyme adopted an entirely novel fold that has not been seen in
      nature, which was published elsewhere. These results highlight the versatility of
      the in vitro selection technique mRNA display as a powerful method for the
      isolation of thermostable novel enzymes.

PMID- 25393376
TI  - EPA-coated titanium implants promote osteoconduction in white New Zealand
      rabbits.
AB  - OBJECTIVES: To investigate the effect of eicosapentaenoic acid (EPA)-coated Ti
      implants on osteoconduction in white New Zealand rabbit mandibles. MATERIAL AND
      METHODS: Sandblasted and cleansed planar titanium specimens with a size of 5 * 5
      * 1 mm were coated on one side with 0.25 vol% eicosapentaenoic acid (EPA). The
      other side of the specimens was kept highly polished (the control side). These
      specimens were inserted in rabbit mandibles. Twelve rabbits were randomly
      assigned into three study groups (n = 4). The rabbits were sacrificed at 4, 8,
      and 12 weeks. The harvested specimens with the implants were assessed for new
      bone formation on both sides of the implant using CBCT, conventional radiographs,
      and the biaxial pullout test. The results were statistically analyzed by a
      nonparametric Kruskal-Wallis test and Friedman's test as multiple comparisons and
      by Brunner-Langer nonparametric mixed model approach (R Software). RESULTS: A
      significant osteoconductive bone formation was found on the EPA-coated Ti implant
      surface (P < 0.05) at 8 weeks when compared to the polished surface (control).
      Biaxial pullout test results showed a significant difference (P < 0.05) after 8
      and 12 weeks with a maximum force of 243.8 N, compared to 143.25 N after 4 week.
      CONCLUSION: EPA implant coating promoted osteoconduction on the Ti implant
      surfaces, enhancing the anchorage of the implant to the surrounding bone in white
      New Zealand rabbits.

PMID- 25393377
TI  - Withdrawing versus not offering cardiopulmonary resuscitation: Is there a
      difference?

PMID- 25393379
TI  - Strong emissive nanofibers of organogels for the detection of volatile acid
      vapors.
AB  - Two L-phenylalanine derivatives with 5,8-bis(2-(carbazol-3-yl)vinyl)quinoxaline
      (PCQ) and 5,8-bis[2-(carbazol-3-yl)]-2,3-dimethylquinoxaline (DCQ) as
      fluorophores were synthesized, and their photophysical properties were measured
      and compared. The two compounds were found to gelate some organic solvents and
      self-assemble into 1D nanofibers in gels. The wet gel of PCQ emitted a weak
      orange fluorescence, but the DCQ gel had a strong green one. This result can be
      due to the presence of two methyl groups and the nonplanar conformation of
      fluorophore in DCQ. The gel film of DCQ also showed significantly stronger
      fluorescence than that of PCQ. Thus, the wet gel and xerogel film of DCQ were
      selected to study their sensing properties to acids. The yellow wet gel of DCQ
      transformed into a brown sol upon the addition of 0.2 equiv trifluoroacetic acid
      (TFA), accompanied by emission quenching. The xerogel film of DCQ rapidly
      responded to volatile acids, such as TFA, HCl, and HOAc. The fluorescence of the
      xerogel film was gradually quenched with increased concentration of volatile acid
      vapors. The fibrous film exhibited low detection limits for volatile acid. The
      detection limits of the thin films for TFA, HCl, and HOAc reached 43, 122, and
      950 ppb, respectively. 

PMID- 25393380
TI  - Influence of a multiple emulsion, liposomes and a microemulsion gel on sebum,
      skin hydration and TEWL.
AB  - OBJECTIVE: In this study, the influence of three cosmetically relevant, priorly
      characterized vehicles on skin hydration, sebum content and transepidermal water
      loss was investigated. The chosen vehicles included a liposomal pre-formulation,
      a multiple W/O/W emulsion and a microemulsion gel. The in vivo effects of these
      vehicles were demonstrated and compared among them. METHODS: The stability of the
      prepared vehicles was determined visually, microscopically, rheologically by pH
      measurements and particle size. Interactions with skin were assessed by non
      invasive biophysical techniques using the Corneometer((r)), Aqua Flux((r)) and
      Sebumeter, measuring skin hydration, TEWL and skin sebum content, respectively.
      RESULTS: All vehicles remained stable over an observation period of 6 weeks. The
      multiple emulsion increased sebum content and skin hydration. In case of the
      liposomes, each monitored parameter remained almost constant. In contrast, the
      microemulsion gel lowered skin hydration and increased TEWL values, but even 1
      week after termination of the treatment TEWL decreased almost close to control
      levels. CONCLUSION: All produced vehicles were proven to remain physically stable
      over the duration of this study. The used multiple emulsion showed very skin
      friendly properties by increasing sebum and skin hydration. Likewise, the
      liposomal pre-formulation exhibited no negative effects. On the contrary, the
      investigated microemulsion gel seemed to have skin dehydrating and TEWL
      increasing features. However, the multiple emulsion as well as liposomes was
      identified to be well-tolerated vehicles for skin which might qualify them for
      the use in cosmetic formulations.

PMID- 25393383
TI  - Forward for the "papers from the membership of the northeastern society of
      plastic surgeons" supplement.

PMID- 25393378
TI  - Association of sickle cell trait with chronic kidney disease and albuminuria in
      African Americans.
AB  - IMPORTANCE: The association between sickle cell trait (SCT) and chronic kidney
      disease (CKD) is uncertain. OBJECTIVE: To describe the relationship between SCT
      and CKD and albuminuria in self-identified African Americans. DESIGN, SETTING,
      AND PARTICIPANTS: Using 5 large, prospective, US population-based studies (the
      Atherosclerosis Risk in Communities Study [ARIC, 1987-2013; n = 3402], Jackson
      Heart Study [JHS, 2000-2012; n = 2105], Coronary Artery Risk Development in Young
      Adults [CARDIA, 1985-2006; n = 848], Multi-Ethnic Study of Atherosclerosis [MESA,
      2000-2012; n = 1620], and Women's Health Initiative [WHI, 1993-2012; n = 8000]),
      we evaluated 15,975 self-identified African Americans (1248 participants with SCT
      [SCT carriers] and 14,727 participants without SCT [noncarriers]). MAIN OUTCOMES
      AND MEASURES: Primary outcomes were CKD (defined as an estimated glomerular
      filtration rate [eGFR] of <60 mL/min/1.73 m2 at baseline or follow-up), incident
      CKD, albuminuria (defined as a spot urine albumin:creatinine ratio of >30 mg/g or
      albumin excretion rate >30 mg/24 hours), and decline in eGFR (defined as a
      decrease of >3 mL/min/1.73 m2 per year). Effect sizes were calculated separately
      for each cohort and were subsequently meta-analyzed using a random-effects model.
      RESULTS: A total of 2233 individuals (239 of 1247 SCT carriers [19.2%] vs 1994 of
      14,722 noncarriers [13.5%]) had CKD, 1298 (140 of 675 SCT carriers [20.7%] vs
      1158 of 8481 noncarriers [13.7%]) experienced incident CKD, 1719 (150 of 665 SCT
      carriers [22.6%] vs 1569 of 8249 noncarriers [19.0%]) experienced decline in
      eGFR, and 1322 (154 of 485 SCT carriers [31.8%] vs 1168 of 5947 noncarriers
      [19.6%]) had albuminuria during the study period. Individuals with SCT had an
      increased risk of CKD (odds ratio [OR], 1.57 [95% CI, 1.34-1.84]; absolute risk
      difference [ARD], 7.6% [95% CI, 4.7%-10.8%]), incident CKD (OR, 1.79 [95% CI,
      1.45-2.20]; ARD, 8.5% [95% CI, 5.1%-12.3%]), and decline in eGFR (OR, 1.32 [95%
      CI, 1.07-1.61]; ARD, 6.1% [95% CI, 1.4%-13.0%]) compared with noncarriers. Sickle
      cell trait was also associated with albuminuria (OR, 1.86 [95% CI, 1.49-2.31];
      ARD, 12.6% [95% CI, 7.7%-17.7%]). CONCLUSIONS AND RELEVANCE: Among African
      Americans in these cohorts, the presence of SCT was associated with an increased
      risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers. These
      findings suggest that SCT may be associated with the higher risk of kidney
      disease in African Americans.

PMID- 25393382
TI  - Cell factory applications of the yeast Kluyveromyces marxianus for the
      biotechnological production of natural flavour and fragrance molecules.
AB  - Kluyveromyces marxianus is emerging as a new platform organism for the production
      of flavour and fragrance (F&F) compounds. This food-grade yeast has advantageous
      traits, such as thermotolerance and rapid growth, that make it attractive for
      cell factory applications. The major impediment to its development has been
      limited fundamental knowledge of its genetics and physiology, but this is rapidly
      changing. K. marxianus produces a wide array of volatile molecules and
      contributes to the flavour of a range of different fermented beverages. Advantage
      is now being taken of this to develop strains for the production of metabolites
      such as 2-phenylethanol and ethyl acetate. Strains that were selected from
      initial screens were used to optimize processes for production of these F&F
      molecules. Most developments have focused on optimizing growth conditions and the
      fermentation process, including product removal, with future advancement likely
      to involve development of new strains through the application of evolutionary or
      rational engineering strategies. This is being facilitated by new genomic and
      molecular tools. Furthermore, synthetic biology offers a route to introduce new
      biosynthetic pathways into this yeast for F&F production. Consumer demand for
      biologically-synthesized molecules for use in foods and other products creates an
      opportunity to exploit the unique potential of K. marxianus for this cell factory
      application.

PMID- 25393381
TI  - Thermoresponsive self-assembly of nanostructures from a collagen-like peptide
      containing diblock copolymer.
AB  - Temperature-triggered formation of nanostructures with distinct biological
      activity offers opportunities in selective modification of matrices and in drug
      delivery. Toward these ends, diblock polymers comprising poly(diethylene glycol
      methyl ether methacrylate) (PDEGMEMA) conjugated to a triple helix-forming
      collagen-like peptide were produced. Triggered by the collapse of the
      thermoresponsive domain above its LCST, the conjugate undergoes a reversible
      transition in aqueous solution to form well-defined nanovesicles with diameters
      of approximately 100 nm, with a transition temperature of 37  degrees C. The
      incorporation of CLP domains in these nanostructures may offer opportunities for
      the selective targeting of collagen-containing matrices.

PMID- 25393384
TI  - Complex wound management in ventricular assist device (VAD) patients: the role of
      aggressive debridement and vascularized soft tissue coverage.
AB  - BACKGROUND: Infections and complex wounds after ventricular assist device (VAD)
      placement can result in significant morbidity and mortality. The purpose of this
      study was to evaluate complex wound management in the VAD patient, and to
      describe a treatment protocol for these challenging and potentially mortal
      complications. METHODS: A retrospective study was performed to examine all
      patients who underwent continuous flow, second-generation VAD placement at the
      Hospital of the University of Pennsylvania between March 2008 and April 2013.
      RESULTS: Overall, 150 VADs were placed, with 12 (8%) patients requiring 15
      operative interventions by the plastic surgery services. The most common
      indication for operative intervention was a complicated wound with VAD exposure
      (5/12, 41.7%). All patients underwent aggressive operative debridement, and 11/12
      (92%) underwent vascularized soft tissue coverage. Flaps commonly utilized
      included rectus abdominus myocutaneous (n = 4), rectus abdominus muscle (n = 4),
      pectoralis major (n = 3), and omentum (n = 3). Three patients experienced
      complications which required a return to the operating room, including 1 flap
      loss, 1 hematoma, and 1 wound dehiscence requiring further soft tissue coverage.
      Salvage was achieved, yet a 50% mortality rate in follow-up was noted.
      CONCLUSION: Complex wound management in VAD patients can be achieved with
      aggressive debridement and vascularized soft tissue coverage, most commonly
      utilizing well-vascularized rectus abdominus muscle or omental flaps. Plastic
      surgeons should be familiar with the armamentarium at their disposal when
      approaching these challenging cases as VAD wound complications stand to become an
      increasingly prevalent issue.

PMID- 25393386
TI  - Recent advances in neurology 2013-2014.

PMID- 25393385
TI  - Power and sample size calculations for the Wilcoxon-Mann-Whitney test in the
      presence of death-censored observations.
AB  - We consider a clinical trial of a potentially lethal disease in which patients
      are randomly assigned to two treatment groups and are followed for a fixed period
      of time; a continuous endpoint is measured at the end of follow-up. For some
      patients; however, death (or severe disease progression) may preclude measurement
      of the endpoint. A statistical analysis that includes only patients with endpoint
      measurements may be biased. An alternative analysis includes all randomized
      patients, with rank scores assigned to the patients who are available for the
      endpoint measurement on the basis of the magnitude of their responses and with
      'worst-rank' scores assigned to those patients whose death precluded the
      measurement of the continuous endpoint. The worst-rank scores are worse than all
      observed rank scores. The treatment effect is then evaluated using the Wilcoxon
      Mann-Whitney test. In this paper, we derive closed-form formulae for the power
      and sample size of the Wilcoxon-Mann-Whitney test when missing measurements of
      the continuous endpoints because of death are replaced by worst-rank scores. We
      distinguish two approaches for assigning the worst-rank scores. In the tied worst
      rank approach, all deaths are weighted equally, and the worst-rank scores are set
      to a single value that is worse than all measured responses. In the untied worst
      rank approach, the worst-rank scores further rank patients according to their
      time of death, so that an earlier death is considered worse than a later death,
      which in turn is worse than all measured responses. In addition, we propose four
      methods for the implementation of the sample size formulae for a trial with
      expected early death. We conduct Monte Carlo simulation studies to evaluate the
      accuracy of our power and sample size formulae and to compare the four sample
      size estimation methods.

PMID- 25393387
TI  - Association between Helicobacter pylori burden and Alzheimer's disease.

PMID- 25393388
TI  - Response to comment: 'Association between Helicobacter pylori burden and
      Alzheimer's disease'.

PMID- 25393389
TI  - Interpretation of post-anoxic somatosensory evoked potentials--leave it to the
      experts!

PMID- 25393392
TI  - Synthetic-method-dependent magnetic relaxation in a cobalt(II) phosphonate chain
      compound.
AB  - A polar cobalt(II) phosphonate Co(bamdpH2)(H2O) (1) [bamdpH4 =
      (benzylazanediyl)bis(methylene)diphosphonic acid] is reported. It shows a linear
      chain structure. The neighboring chains are connected by moderately strong
      hydrogen bonds forming a supramolecular layer. The interlayer spaces are filled
      with the organic groups of the phosphonate ligands. Compound 1 displays the
      coexistence of single-chain magnet behavior and canted antiferromagnetism below
      2.8 K. Moreover, the magnetic dynamics is strongly dependent on the synthetic
      methods, a phenomenon that has not been documented before. 

PMID- 25393391
TI  - Pluripotent states of human embryonic stem cells.
AB  - Since human embryonic stem cells (hESCs) were first isolated and successfully
      cultured in vitro, the pluripotent potential of hESCs has been underestimated.
      The pluripotency of mouse embryonic stem cells (mESCs) can be categorized as
      naive and primed, depending on their corresponding in vivo developing phases.
      mESC morphology differs at distinct pluripotent states, which differ in signaling
      dependence, gene expression, epigenetic features, and developmental potential.
      hESCs resemble mouse stem cells at primed pluripotency, and consequently are
      believed to correspond to a later developmental stage in vivo than mESCs.
      Nevertheless, recent studies indicate that a naive state of pluripotency may
      exist in hESCs, and the pluripotency of hESCs also can be enhanced by genetic
      modification or optimized culture systems. These findings provide novel insight
      into the properties and differentiation potential of hESCs. Here, we review the
      recent advances in characterization of ESC states and investigate the mechanisms
      regulating hESC pluripotency. 

PMID- 25393393
TI  - Abdominal variant of benign symmetric lipomatosis (Launois-Bensaude syndrome)
      imitating obesity.

PMID- 25393394
TI  - Synthesis of functionalized cyanopyrazoles via magnesium bases.
AB  - 4-Alkyl- and 4-H-pyrazoles were sequentially metalated using TMPMgCl.LiCl, and
      their reaction with electrophiles afforded 3-aryl-4-alkyl-5-cyanopyrazoles. 

PMID- 25393395
TI  - Gender differences in the relationship between affect and adolescent smoking
      uptake.
AB  - AIMS: To evaluate gender differences in the role of positive and negative affect
      on smoking uptake. DESIGN: Prospective longitudinal cohort study of adolescent
      health behaviors. SETTING: Four suburban secondary schools outside Philadelphia,
      Pennsylvania, USA. PARTICIPANTS: Adolescents (n = 1357) were surveyed every 6
      months for 4 years (age 14-18 years). MEASUREMENTS: Smoking and affect were
      measured via survey at each of the eight time-points. FINDINGS: A two-group
      associative process latent growth curve model revealed that baseline positive
      affect was related negatively to smoking progression for females (b = -0.031, Z =
      -4.00, P < 0.0001) but not for males (P = 0.33). This gender difference was
      significant, chi(2)((df = 1))  = 8.24, P = 0.0041, indicating that for every
      standard deviation (SD) decrease in positive affect (SD = 2.90), there was a 10%
      increase [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.04, 1.14] in
      the odds of smoking progression for females. Baseline negative affect was related
      significantly and positively to smoking progression for males (b = 0.038, Z
      =2.874, P = 0.004) and females (b = 0.025, Z =3.609, P < 0.0001), but the gender
      difference was not significant, chi(2)((df = 1)) = 0.82, P = 0.37. Thus, on
      average, for every standard deviation (SD = 4.40) increase in baseline negative
      affect there was a 15% (OR = 1.15, 95% CI = 1.06, 1.26) increase in the odds of
      smoking progression for males and for females. CONCLUSIONS: The impact of affect
      on adolescent smoking uptake varies by gender. Low positive affect (low
      experience of positive feelings or emotions) for females and high negative affect
      (high experience of negative feelings or emotions) for both males and females
      increases the risk for adolescent smoking.

PMID- 25393396
TI  - Mapping current and potential distribution of non-native Prosopis juliflora in
      the Afar region of Ethiopia.
AB  - We used correlative models with species occurrence points, Moderate Resolution
      Imaging Spectroradiometer (MODIS) vegetation indices, and topo-climatic
      predictors to map the current distribution and potential habitat of invasive
      Prosopis juliflora in Afar, Ethiopia. Time-series of MODIS Enhanced Vegetation
      Indices (EVI) and Normalized Difference Vegetation Indices (NDVI) with 250 m2
      spatial resolution were selected as remote sensing predictors for mapping
      distributions, while WorldClim bioclimatic products and generated topographic
      variables from the Shuttle Radar Topography Mission product (SRTM) were used to
      predict potential infestations. We ran Maxent models using non-correlated
      variables and the 143 species- occurrence points. Maxent generated probability
      surfaces were converted into binary maps using the 10-percentile logistic
      threshold values. Performances of models were evaluated using area under the
      receiver-operating characteristic (ROC) curve (AUC). Our results indicate that
      the extent of P. juliflora invasion is approximately 3,605 km2 in the Afar region
      (AUC  = 0.94), while the potential habitat for future infestations is 5,024 km2
      (AUC  = 0.95). Our analyses demonstrate that time-series of MODIS vegetation
      indices and species occurrence points can be used with Maxent modeling software
      to map the current distribution of P. juliflora, while topo-climatic variables
      are good predictors of potential habitat in Ethiopia. Our results can quantify
      current and future infestations, and inform management and policy decisions for
      containing P. juliflora. Our methods can also be replicated for managing invasive
      species in other East African countries. 

PMID- 25393398
TI  - Mono(imidazolin-2-iminato) actinide complexes: synthesis and application in the
      catalytic dimerization of aldehydes.
AB  - The synthesis of the mono(imidazolin-2-iminato) actinide(IV) complexes
      [(Im(R)N)An(N{SiMe3)2}3] (3-8) was accomplished by the protonolysis reaction
      between the respective imidazolin-2-imine (Im(R)NH, R = tBu, Mes, Dipp) and the
      actinide metallacycles [{(Me3Si)N}2An{kappa(2)C,N-CH2SiMe2N(SiMe3)}] (1, An = U;
      2, M = Th). The thorium and uranium complexes were obtained in high yields, and
      their structures were established by single-crystal X-ray diffraction analysis.
      The mono(imidazolin-2-iminato) actinide complexes 3-8 display short An-N bonds
      together with large An-N-C angles, indicating strong electron donation from the
      imidazolin-2-iminato moiety to the metal, corroborating a substantial pi
      character to the An-N bond. The reactivity of complexes 3-8 toward benzaldehyde
      was studied in the catalytic dimerization of aldehydes (Tishchenko reaction),
      displaying low to moderate catalytic activities for the uranium complexes 3-5 and
      moderate to high catalytic activities for the thorium analogues 6-8, among which
      8 exhibited the highest catalytic activity. In addition, actinide coordination
      compounds showed unprecedented reactivity toward cyclic and branched aliphatic
      aldehydes in the catalytic Tishchenko reaction mediated by the thorium complex
      [(Im(Dipp)N)Th{N(SiMe3)2}3] (8), exhibiting high activity even at room
      temperature. Moreover, complex 8 was successfully applied in the crossed
      Tishchenko reaction between an aromatic or polyaromatic and an aliphatic cyclic
      and branched aldehyde, yielding selectively the asymmetrically substituted ester
      in high yields (80-100%). 

PMID- 25393397
TI  - An analysis of glucocorticoid receptor-mediated gene expression in BEAS-2B human
      airway epithelial cells identifies distinct, ligand-directed, transcription
      profiles with implications for asthma therapeutics.
AB  - BACKGROUND AND PURPOSE: International asthma guidelines recommend that inhaled
      glucocorticoids be used as a monotherapy in all patients with mild to moderate
      disease because of their ability to suppress airways inflammation. Current
      evidence suggests that the therapeutic benefit of glucocorticoids is due to the
      transactivation and transrepression of anti-inflammatory and pro-inflammatory
      genes respectively. However, the extent to which clinically relevant
      glucocorticoids are equivalent in their ability to modulate gene expression is
      unclear. EXPERIMENTAL APPROACH: A pharmacodynamics investigation of
      glucocorticoid receptor (GR)-mediated gene transactivation in BEAS-2B human
      airway epithelial cells was performed using a glucocorticoid response element
      luciferase reporter coupled with an analysis of glucocorticoid-inducible genes
      encoding proteins with anti-inflammatory and adverse-effect potential. KEY
      RESULTS: Using transactivation as a functionally relevant output, a given
      glucocorticoid displayed a unique, gene expression 'fingerprint' where intrinsic
      efficacy and GR density were essential determinants. We showed that depending on
      the gene selected for analysis, a given glucocorticoid can behave as an
      antagonist, partial agonist, full agonist or even 'super agonist'. In the likely
      event that different, tissue-dependent gene expression profiles are reproduced in
      vivo, then the anti-inflammatory and adverse-effect potential of many
      glucocorticoids currently available as asthma therapeutics may not be equivalent.
      CONCLUSIONS AND IMPLICATIONS: The generation of gene expression 'fingerprints' in
      target and off-target human tissues could assist the rational design of GR
      agonists with improved therapeutic ratios. This approach could identify compounds
      that are useful in the management of severe asthma and other inflammatory
      disorders where systemic exposure is desirable.

PMID- 25393399
TI  - Platelets and fibrin in progression of liver disease: friends or foes?

PMID- 25393400
TI  - Surgical and antimicrobial treatment of prosthetic vascular graft infections at
      different surgical sites: a retrospective study of treatment outcomes.
AB  - OBJECTIVE: Little is known about optimal management of prosthetic vascular graft
      infections, which are a rare but serious complication associated with graft
      implants. The goal of this study was to compare and characterize these infections
      with respect to the location of the graft and to identify factors associated with
      outcome. METHODS: This was a retrospective study over more than a decade at a
      tertiary care university hospital that has an established multidisciplinary
      approach to treating graft infections. Cases of possible prosthetic vascular
      graft infection were identified from the hospital's infectious diseases database
      and evaluated against strict diagnostic criteria. Patients were divided into
      groups according to the locations of their grafts: thoracic-aortic, abdominal
      aortic, or peripheral-arterial. Statistical analyses included evaluation of
      patient and infection characteristics, time to treatment failure, and factors
      associated specifically with cure rates in aortic graft infections. The primary
      endpoint was cure at one year after diagnosis of the infection. RESULTS:
      Characterization of graft infections according to the graft location did show
      that these infections differ in terms of their characteristics and that the
      prognosis for treatment seems to be influenced by the location of the infection.
      Cure rate and all-cause mortality at one year were 87.5% and 12.5% in 24 patients
      with thoracic-aortic graft infections, 37.0% and 55.6% in 27 patients with
      abdominal-aortic graft infections, and 70.0% and 30.0% in 10 patients with
      peripheral-arterial graft infections. In uni- and multivariate analysis, the type
      of surgical intervention used in managing infections (graft retention versus
      graft replacement) did not affect primary outcome, whereas a rifampicin-based
      antimicrobial regimen was associated with a higher cure rate. CONCLUSIONS: We
      recommend that future prospective studies differentiate prosthetic vascular graft
      infections according to the location of the grafts and that rifampicin-based
      antimicrobial regimens be evaluated in clinical trials involving vascular graft
      infections caused by staphylococci.

PMID- 25393401
TI  - Three-Dimensional Mapping of mRNA Export through the Nuclear Pore Complex.
AB  - The locations of transcription and translation of mRNA in eukaryotic cells are
      spatially separated by the nuclear envelope (NE). Plenty of nuclear pore
      complexes (NPCs) embedded in the NE function as the major gateway for the export
      of transcribed mRNAs from the nucleus to the cytoplasm. Whereas the NPC, perhaps
      one of the largest protein complexes, provides a relatively large channel for
      macromolecules to selectively pass through it in inherently three-dimensional
      (3D) movements, this channel is nonetheless below the diffraction limit of
      conventional light microscopy. A full understanding of the mRNA export mechanism
      urgently requires real-time mapping of the 3D dynamics of mRNA in the NPC of live
      cells with innovative imaging techniques breaking the diffraction limit of
      conventional light microscopy. Recently, super-resolution fluorescence microscopy
      and single-particle tracking (SPT) techniques have been applied to the study of
      nuclear export of mRNA in live cells. In this review, we emphasize the necessity
      of 3D mapping techniques in the study of mRNA export, briefly summarize the
      feasibility of current 3D imaging approaches, and highlight the new features of
      mRNA nuclear export elucidated with a newly developed 3D imaging approach
      combining SPT-based super-resolution imaging and 2D-to-3D deconvolution
      algorithms. 

PMID- 25393402
TI  - Expression of CNPY2 in mouse tissues: quantification and localization.
AB  - Canopy FGF signaling regulator 2 (CNPY2) is a FGF21-modulated protein containing
      a saposin B-type domain. In vitro studies have shown CNPY2 is able to enhance
      neurite outgrowth in neurons and stabilize the expression of low density
      lipoprotein receptor in macrophages and hepatocytes. However, no in vivo data are
      available on the normal expression of CNPY2 and information is lacking on which
      cell types express this protein in tissues. To address this, the present study
      examined CNPY2 expression at the mRNA and protein levels. Quantitative PCR and
      ELISA examination of mouse tissues showed that CNPY2 varies between organs, with
      the highest expression in the heart, lung and liver. Immunohistochemistry
      detected CNPY2 in a variety of cell types including skeletal, cardiac and smooth
      muscle myocytes, endothelial cells and epithelial cells. CNPY2 was also
      detectable in mouse blood and human and mouse uteri. These data demonstrate CNPY2
      is widely distributed in tissues and suggest the protein has biological functions
      that have yet to be identified. Using these new observations we discuss possible
      functions of the protein. 

PMID- 25393403
TI  - Distinct modes of transmission of tuberculosis in aboriginal and non-aboriginal
      populations in Taiwan.
AB  - Tuberculosis incidence among aborigines is significantly higher than for Han
      Chinese in Taiwan, but the extent to which Mycobacterium tuberculosis (MTB)
      strain characteristics contribute to this difference is not well understood. MTB
      isolates from aborigines and Han Chinese living in eastern and southern Taiwan,
      the major regions of aborigines, were analyzed by spoligotyping and 24-loci MIRU
      VNTR. In eastern Taiwan, 60% of aboriginal patients were <=20 years old,
      significantly younger than the non-aboriginal patients there; aborigines were
      more likely to have clustered MTB isolates than Han Chinese (odds ratio (OR) =
      5.98, p<0.0001). MTB lineages with high clustering were EAI (54.9%) among
      southern people, and Beijing (62.5%) and Haarlem (52.9%) among eastern
      aborigines. Resistance to first-line drugs and multidrug resistance (MDR) were
      significantly higher among eastern aborigines (>=15%) than in any other
      geographic and ethnic group (p<0.05); MDR was detected in 5 of 28 eastern
      aboriginal patients <=20 years old. Among patients from the eastern region,
      clustered strains (p = 0.01) and aboriginal ethnicity (p = 0.04) were independent
      risk factors for MDR. The lifestyles of aborigines in eastern Taiwan may explain
      why the percentage of infected aborigines is much higher than for their Han
      Chinese counterparts. The significantly higher percentage of the MDR-MTB strains
      in the aboriginal population warrants close attention to control policy and
      vaccination strategy. 

PMID- 25393404
TI  - A comprehensive assessment of lymphatic filariasis in Sri Lanka six years after
      cessation of mass drug administration.
AB  - BACKGROUND: The Sri Lankan Anti-Filariasis Campaign conducted 5 rounds of mass
      drug administration (MDA) with diethycarbamazine plus albendazole between 2002
      and 2006. We now report results of a comprehensive surveillance program that
      assessed the lymphatic filariasis (LF) situation in Sri Lanka 6 years after
      cessation of MDA. METHODOLOGY AND PRINCIPAL FINDINGS: Transmission assessment
      surveys (TAS) were performed per WHO guidelines in primary school children in 11
      evaluation units (EUs) in all 8 formerly endemic districts. All EUs easily
      satisfied WHO criteria for stopping MDA. Comprehensive surveillance was performed
      in 19 Public Health Inspector (PHI) areas (subdistrict health administrative
      units). The surveillance package included cross-sectional community surveys for
      microfilaremia (Mf) and circulating filarial antigenemia (CFA), school surveys
      for CFA and anti-filarial antibodies, and collection of Culex mosquitoes with
      gravid traps for detection of filarial DNA (molecular xenomonitoring, MX).
      Provisional target rates for interruption of LF transmission were community CFA
      <2%, antibody in school children <2%, and filarial DNA in mosquitoes <0.25%.
      Community Mf and CFA prevalence rates ranged from 0-0.9% and 0-3.4%,
      respectively. Infection rates were significantly higher in males and lower in
      people who denied prior treatment. Antibody rates in school children exceeded 2%
      in 10 study sites; the area that had the highest community and school CFA rates
      also had the highest school antibody rate (6.9%). Filarial DNA rates in
      mosquitoes exceeded 0.25% in 10 PHI areas. CONCLUSIONS: Comprehensive
      surveillance is feasible for some national filariasis elimination programs. Low
      level persistence of LF was present in all study sites; several sites failed to
      meet provisional endpoint criteria for LF elimination, and follow-up testing will
      be needed in these areas. TAS was not sensitive for detecting low-level
      persistence of filariasis in Sri Lanka. We recommend use of antibody and MX
      testing as tools to complement TAS for post-MDA surveillance.

PMID- 25393405
TI  - The skin microbiome: a focus on pathogens and their association with skin
      disease.

PMID- 25393406
TI  - Yeast Pif1 accelerates annealing of complementary DNA strands.
AB  - Pif1 is a helicase involved in the maintenance of nuclear and mitochondrial
      genomes in eukaryotes. Here we report a new activity of Saccharomyces cerevisiae
      Pif1, annealing of complementary DNA strands. We identified preferred substrates
      for annealing as those that generate a duplex product with a single-stranded
      overhang relative to a blunt end duplex. Importantly, we show that Pif1 can
      anneal DNA in the presence of ATP and Mg(2+). Pif1-mediated annealing also occurs
      in the presence of single-stranded DNA binding proteins. Additionally, we show
      that partial duplex substrates with 3'-single-stranded overhangs such as those
      generated during double-strand break repair can be annealed by Pif1. 

PMID- 25393407
TI  - High-level production of beta-1,3-1,4-glucanase by Rhizomucor miehei under solid
      state fermentation and its potential application in the brewing industry.
AB  - AIMS: To improve the beta-1,3-1,4-glucanase production by Rhizomucor miehei under
      solid-state fermentation (SSF) for industrial application. METHODS AND RESULTS:
      The fermentation conditions for beta-1,3-1,4-glucanase production by R. miehei
      CAU432 under SSF were optimized using a 'one-factor-at-a-time' method. Under the
      optimized fermentation conditions, viz. oatmeal (0.45-0.9 mm) as sole carbon
      source, 5% (w/w) peptone as sole nitrogen source, initial moisture of 80% (w/w),
      initial culture pH of 5.0, incubation temperature of 50 degrees C and incubation
      time of 6 days, the highest beta-1,3-1,4-glucanase activity of 20,025 U g(-1) dry
      substrate was achieved, which represents the highest yield for beta-1,3-1,4
      glucanase production ever reported. The crude enzyme was extracted and purified
      to homogeneity with a purification fold of 4.6 and a recovery yield of 9.0%. The
      addition of the purified beta-1,3-1,4-glucanase in mash obviously reduced its
      filtration time (24.6%) and viscosity (2.61%). CONCLUSIONS: The optimal
      fermentation conditions for maximal beta-1,3-1,4-glucanase production under SSF
      was obtained, and the enzyme was suitable for application in the malting process.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The high production yield and excellent
      capability of the enzyme may enable it great potential in industries, especially
      in brewing industry.

PMID- 25393408
TI  - In the multi-domain protein adenylate kinase, domain insertion facilitates
      cooperative folding while accommodating function at domain interfaces.
AB  - Having multiple domains in proteins can lead to partial folding and increased
      aggregation. Folding cooperativity, the all or nothing folding of a protein, can
      reduce this aggregation propensity. In agreement with bulk experiments, a coarse
      grained structure-based model of the three-domain protein, E. coli Adenylate
      kinase (AKE), folds cooperatively. Domain interfaces have previously been
      implicated in the cooperative folding of multi-domain proteins. To understand
      their role in AKE folding, we computationally create mutants with deleted inter
      domain interfaces and simulate their folding. We find that inter-domain
      interfaces play a minor role in the folding cooperativity of AKE. On further
      analysis, we find that unlike other multi-domain proteins whose folding has been
      studied, the domains of AKE are not singly-linked. Two of its domains have two
      linkers to the third one, i.e., they are inserted into the third one. We use
      circular permutation to modify AKE chain-connectivity and convert inserted
      domains into singly-linked domains. We find that domain insertion in AKE achieves
      the following: (1) It facilitates folding cooperativity even when domains have
      different stabilities. Insertion constrains the N- and C-termini of inserted
      domains and stabilizes their folded states. Therefore, domains that perform
      conformational transitions can be smaller with fewer stabilizing interactions.
      (2) Inter-domain interactions are not needed to promote folding cooperativity and
      can be tuned for function. In AKE, these interactions help promote conformational
      dynamics limited catalysis. Finally, using structural bioinformatics, we suggest
      that domain insertion may also facilitate the cooperative folding of other multi
      domain proteins. 

PMID- 25393409
TI  - Genomic signal processing methods for computation of alignment-free distances
      from DNA sequences.
AB  - Genomic signal processing (GSP) refers to the use of digital signal processing
      (DSP) tools for analyzing genomic data such as DNA sequences. A possible
      application of GSP that has not been fully explored is the computation of the
      distance between a pair of sequences. In this work we present GAFD, a novel GSP
      alignment-free distance computation method. We introduce a DNA sequence-to-signal
      mapping function based on the employment of doublet values, which increases the
      number of possible amplitude values for the generated signal. Additionally, we
      explore the use of three DSP distance metrics as descriptors for categorizing DNA
      signal fragments. Our results indicate the feasibility of employing GAFD for
      computing sequence distances and the use of descriptors for characterizing DNA
      fragments. 

PMID- 25393410
TI  - Different effects of adding white noise on cognitive performance of sub-, normal
      and super-attentive school children.
AB  - OBJECTIVES: Noise often has detrimental effects on performance. However, because
      of the phenomenon of stochastic resonance (SR), auditory white noise (WN) can
      alter the "signal to noise" ratio and improve performance. The Moderate Brain
      Arousal (MBA) model postulates different levels of internal "neural noise" in
      individuals with different attentional capacities. This in turn determines the
      particular WN level most beneficial in each individual case-with one level of WN
      facilitating poor attenders but hindering super-attentive children. The objective
      of the present study is to find out if added WN affects cognitive performance
      differently in children that differ in attention ability. METHODS: Participants
      were teacher-rated super- (N = 25); normal- (N = 29) and sub-attentive (N = 36)
      children (aged 8 to 10 years). Two non-executive function (EF) tasks (a verbal
      episodic recall task and a delayed verbal recognition task) and two EF tasks (a
      visuo-spatial working memory test and a Go-NoGo task) were performed under three
      WN levels. The non-WN condition was only used to control for potential
      differences in background noise in the group testing situations. RESULTS: There
      were different effects of WN on performance in the three groups-adding moderate
      WN worsened the performance of super-attentive children for both task types and
      improved EF performance in sub-attentive children. The normal-attentive
      children's performance was unaffected by WN exposure. The shift from moderate to
      high levels of WN had little further effect on performance in any group.
      SIGNIFICANCE: The predicted differential effect of WN on performance was
      confirmed. However, the failure to find evidence for an inverted U function
      challenges current theories. Alternative explanations are discussed. We propose
      that WN therapy should be further investigated as a possible non-pharmacological
      treatment for inattention.

PMID- 25393411
TI  - Circulatory responses to asphyxia differ if the asphyxia occurs in utero or ex
      utero in near-term lambs.
AB  - BACKGROUND: A cornerstone of neonatal resuscitation teaching suggests that a
      rapid vagal-mediated bradycardia is one of the first signs of perinatal
      compromise. As this understanding is based primarily on fetal studies, we
      investigated whether the heart rate and blood pressure response to total asphyxia
      is influenced by whether the animal is in utero or ex utero. METHODS: Fetal sheep
      were instrumented at ~ 139 days of gestation and then asphyxiated by umbilical
      cord occlusion until mean arterial blood pressure decreased to ~ 20 mmHg. Lambs
      were either completely submerged in amniotic fluid (in utero; n = 8) throughout
      the asphyxia or were delivered and then remained ex utero (ex utero; n = 8)
      throughout the asphyxia. Heart rate and arterial blood pressure were continuously
      recorded. RESULTS: Heart rate was higher in ex utero lambs than in utero lambs.
      Heart rates in in utero lambs rapidly decreased, while heart rates in ex utero
      lambs initially increased following cord occlusion (for ~ 1.5 min) before they
      started to decrease. Mean arterial pressure initially increased then decreased in
      both groups. CONCLUSIONS: Heart rate response to asphyxia was markedly different
      depending upon whether the lamb was in utero or ex utero. This indicates that the
      cardiovascular responses to perinatal asphyxia are significantly influenced by
      the newborn's local environment. As such, based solely on heart rate, the stage
      and severity of a perinatal asphyxic event may not be as accurate as previously
      assumed.

PMID- 25393413
TI  - A highly cis-selective and enantioselective metal-free hydrogenation of 2,3
      disubstituted quinoxalines.
AB  - A wide range of 2,3-disubstituted quinoxalines have been successfully
      hydrogenated with H2 using borane catalysts to produce the desired
      tetrahydroquinoxalines in 80-99% yields with excellent cis selectivity.
      Significantly, the asymmetric reaction employing chiral borane catalysts
      generated by the in situ hydroboration of chiral dienes with HB(C6F5)2 under mild
      reaction conditions has also been achieved with up to 96% ee, and represents the
      first catalytic asymmetric system to furnish optically active cis-2,3
      disubstituted 1,2,3,4-tetrahydroquinoxalines.

PMID- 25393412
TI  - Phylogenetically driven sequencing of extremely halophilic archaea reveals
      strategies for static and dynamic osmo-response.
AB  - Organisms across the tree of life use a variety of mechanisms to respond to
      stress-inducing fluctuations in osmotic conditions. Cellular response mechanisms
      and phenotypes associated with osmoadaptation also play important roles in
      bacterial virulence, human health, agricultural production and many other
      biological systems. To improve understanding of osmoadaptive strategies, we have
      generated 59 high-quality draft genomes for the haloarchaea (a euryarchaeal clade
      whose members thrive in hypersaline environments and routinely experience drastic
      changes in environmental salinity) and analyzed these new genomes in combination
      with those from 21 previously sequenced haloarchaeal isolates. We propose a
      generalized model for haloarchaeal management of cytoplasmic osmolarity in
      response to osmotic shifts, where potassium accumulation and sodium expulsion
      during osmotic upshock are accomplished via secondary transport using the proton
      gradient as an energy source, and potassium loss during downshock is via a
      combination of secondary transport and non-specific ion loss through
      mechanosensitive channels. We also propose new mechanisms for magnesium and
      chloride accumulation. We describe the expansion and differentiation of
      haloarchaeal general transcription factor families, including two novel
      expansions of the TATA-binding protein family, and discuss their potential for
      enabling rapid adaptation to environmental fluxes. We challenge a recent high
      profile proposal regarding the evolutionary origins of the haloarchaea by showing
      that inclusion of additional genomes significantly reduces support for a proposed
      large-scale horizontal gene transfer into the ancestral haloarchaeon from the
      bacterial domain. The combination of broad (17 genera) and deep (>=5 species in
      four genera) sampling of a phenotypically unified clade has enabled us to uncover
      both highly conserved and specialized features of osmoadaptation. Finally, we
      demonstrate the broad utility of such datasets, for metagenomics, improvements to
      automated gene annotation and investigations of evolutionary processes.

PMID- 25393414
TI  - A pilot RCT of psychodynamic group art therapy for patients in acute psychotic
      episodes: feasibility, impact on symptoms and mentalising capacity.
AB  - This pilot study aimed to evaluate the feasibility of an assessor-blind,
      randomised controlled trial of psychodynamic art therapy for the treatment of
      patients with schizophrenia, and to generate preliminary data on the efficacy of
      this intervention during acute psychotic episodes. Fifty-eight inpatients with
      DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions
      of psychodynamic group art therapy plus treatment as usual or to standard
      treatment alone. Primary outcome criteria were positive and negative psychotic
      and depressive symptoms as well as global assessment of functioning. Secondary
      outcomes were mentalising function, estimated with the Reading the mind in the
      eyes test and the Levels of emotional awareness scale, self-efficacy, locus of
      control, quality of life and satisfaction with care. Assessments were made at
      baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of
      patients randomised to art therapy, and 66% of patients receiving treatment as
      usual were examined. In the per-protocol sample, art therapy was associated with
      a significantly greater mean reduction of positive symptoms and improved
      psychosocial functioning at post-treatment and follow-up, and with a greater mean
      reduction of negative symptoms at follow-up compared to standard treatment. The
      significant reduction of positive symptoms at post-treatment was maintained in an
      attempted intention-to-treat analysis. There were no group differences regarding
      depressive symptoms. Of secondary outcome parameters, patients in the art therapy
      group showed a significant improvement in levels of emotional awareness, and
      particularly in their ability to reflect about others' emotional mental states.
      This is one of the first randomised controlled trials on psychodynamic group art
      therapy for patients with acute psychotic episodes receiving hospital treatment.
      Results prove the feasibility of trials on art therapy during acute psychotic
      episodes and justify further research to substantiate preliminary positive
      results regarding symptom reduction and the recovery of mentalising function.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01622166.

PMID- 25393415
TI  - Influence of the time of day and fasting duration on glucose level following a 1
      hour, 50-gram glucose challenge test in pregnant women.
AB  - BACKGROUND: Previous studies have shown that the time of day (TD) of glucose
      measurement and the fasting duration (FD) influence the glucose levels in adults.
      Few studies have examined the effects of the TD and FD on the glucose level
      following a 1-hour, 50-gram glucose challenge test (GCT) in pregnant women in
      screening for or diagnosing gestational diabetes mellitus (GDM). The objective of
      this study was to investigate the influence of the TD (morning, afternoon, night)
      and the FD (the time of the last food ingestion as follows: <=1 hour, 1-2 hours,
      and >2 hours) by examining their combined effects on the glucose levels following
      a 50-gram GCT in pregnant women. METHODS AND RESULTS: We analyzed the data of
      1,454 non-diabetic pregnant Taiwanese women in a prospective study. Multiple
      linear regression and multiple logistic regression were used to estimate the
      relationships between the 9 TD-FD groups and the continuous and binary glucose
      levels (cut-off at 140 mg/dL) following a 50-gram GCT, after adjusting for
      maternal age, nulliparity, pre-pregnancy body mass index, and weight gain.
      Different TD and FD groups were associated with variable glucose responses to the
      50-gram GCT, some of which were significant. The estimate coefficients (beta) of
      the TD-FD groups "night, <=1 hr" and "night, 1-2 hr" revealed significantly lower
      glucose concentrations [beta (95% confidence interval [CI]): -6.46 (-12.53, 
      0.38) and -6.85 (-12.50, -1.20)] compared with the "morning, >2 hr" group. The TD
      FD groups "afternoon, <=1 hr" and "afternoon, 1-2 hr" showed significantly lower
      odds ratios (OR) of a positive GCT; the adjusted ORs (95% CI) were 0.54 (0.31
      0.95) and 0.58 (0.35-0.96), respectively. CONCLUSIONS: Our findings demonstrate
      the importance of standardizing the TD and FD for the 1-hour, 50-gram GCT. In
      screening for and diagnosing GDM, the TD and FD are modifiable factors that
      should be considered in clinical practice and epidemiological studies.

PMID- 25393416
TI  - Video-based educational tool improves patient comprehension of common prostate
      health terminology.
AB  - BACKGROUND: Health care providers often counsel prostate cancer patients about
      treatment options with medical terminology. However, studies have demonstrated a
      severe lack of comprehension of these terms, particularly in underserved
      populations. It was hypothesized that a video-based educational tool would
      significantly improve the understanding of key terms related to prostate health
      in a predominantly lower literacy population. METHODS: A software application was
      developed by various experts, including urologists and human-computer interaction
      specialists, to serve as a video-based educational tool emphasizing narrated
      animations to promote understanding of terms related to urinary, bowel, and
      sexual function. This application was viewed by patients recruited from 2 low
      income safety net clinics, where a previously developed survey was administered
      to assess pre- and postintervention levels of comprehension. RESULTS: Fifty-six
      patients with a mean literacy level of 7th to 8th grade completed the study.
      Patients achieved statistically significant improvements in comprehension for the
      majority of the terms after the video intervention, with notable improvements
      including the terms incontinence (from 14% to 50%), bowels (from 14% to 46%), and
      impotence (from 58% to 84%). Patients demonstrated significant gains in their
      understanding of the function of the prostate (from 11% to 30%) and in their
      ability to locate the prostate on anatomic drawings (from 50% to 82%).
      CONCLUSIONS: This video-based educational tool is an effective method for
      overcoming the severe lack of comprehension of prostate health terminology among
      patients. The improvements achieved have the potential to enhance patient
      participation in shared and informed decision making and to support combined
      visual-audio multimedia as a promising tool for prostate cancer education.

PMID- 25393418
TI  - Assessment of the reproductive status of female veiled chameleons (Chamaeleo
      calyptratus) using hormonal, behavioural and physical traits.
AB  - Egg binding is a common reproductive disorder in captive female reptiles leading
      to premature loss of breeding potential, or in severe cases death. It can result
      from failure to ovulate (and reabsorb) follicles; follicular stasis, or failure
      to lay eggs; dystocia. Reproductive status of female veiled chameleons (Chamaeleo
      calyptratus) in a research colony was assessed using enzyme immunoassay (EIA) of
      fecal reproductive hormones (estradiol; E2, progesterone; P, and testosterone; T)
      and their metabolites, ultrasound imaging of the reproductive tract, and
      receptivity to conspecific males. Periods of follicular growth (vitellogenesis)
      corresponded with increasing levels of E2, and following ovulation, a distinct
      change in morphology from round (follicles) to oval (eggs) structures, which was
      accompanied by a surge in P (>20-fold above baseline). P levels remained elevated
      throughout the gravid phase until just prior to oviposition. Length/width ratios
      of follicles and eggs were statistically different, but distinguishing a follicle
      from an egg based on the ratio was unreliable due to a large overlap in values.
      In animals that failed to ovulate on their first cycle, follicles began to recede
      but were not fully reabsorbed and could be distinguished from a second batch of
      follicles based on their echogenicity. Female receptivity to conspecific males
      was not related to cycle stage (i.e., previtellogenesis, vitellogenesis, or
      gravid) or reproductive hormone levels. This study demonstrates the use of
      ultrasonography and reproductive hormone analysis to assess phase of the
      reproductive cycle (pre- or post-ovulatory), or confirm ongoing follicular
      stasis.

PMID- 25393417
TI  - Warfarin is an effective modifier of multiple UDP-glucuronosyltransferase
      enzymes: evaluation of its potential to alter the pharmacokinetics of zidovudine.
AB  - In this study, we aimed to determine the modulatory effects of warfarin (an
      extensively used anticoagulant drug) and its metabolites on UDP
      glucuronosyltransferase (UGT) activity and to assess the potential of warfarin to
      alter the pharmacokinetics of zidovudine (AZT). The effects of warfarin and its
      metabolites on glucuronidation were determined using human and rat liver
      microsomes (HLM and RLM) as well as expressed UGTs. The mechanisms of warfarin
      UGT interactions were explored through kinetic characterization and modeling.
      Pharmacokinetic studies with rats were performed to evaluate the potential of
      warfarin to alter the pharmacokinetics of AZT. We found that warfarin was an
      effective modifier of a panel of UGT enzymes. The effects of warfarin on
      glucuronidation were inhibitory for UGT1A1, 2B7, and 2B17, but activating for
      UGT1A3. Mixed effects were observed for UGT1A7 and 1A9. Consistent with its
      inhibitory effects on UGT2B7 activity, warfarin inhibited AZT glucuronidation in
      HLM (Ki = 74.9-96.3 MUM) and RLM (Ki = 190-230 MUM). Inhibition of AZT
      glucuronidation by UGT2B7, HLM, and RLM was also observed with several
      hydroxylated metabolites of warfarin. Moreover, the systemic exposure (AUC) of
      AZT in rats was increased by a 1.5- to 2.1-fold upon warfarin coadministration.
      The elevated AUC was associated with suppressed glucuronidation that was probably
      attained through a combined action of warfarin and its hydroxylated metabolites.
      In conclusion, the activities of multiple UGT enzymes can be modulated by
      warfarin and the nature of modulation was isoform dependent. Also,
      pharmacokinetic interactions of zidovudine with warfarin were highly possible
      through inhibition of UGT metabolism.

PMID- 25393419
TI  - Physical Activity and Sedentary Behavior Patterns of Singaporean Adolescents.
AB  - BACKGROUND: Adolescents require at least 60 minutes of daily moderate to vigorous
      intensity physical activity (PA) for optimum health benefits. Reduced active and
      increased sedentary time can adversely affect health independently. This study
      investigated the sedentary behavior and physical activity patterns of Singaporean
      adolescents. METHODS: 233 adolescents aged 13 to 15 years participated in the
      study. Accelerometry was used to assess the daily PA patterns for 3 weekdays and
      2 weekend days consecutively. Height, weight, BMI, waist circumference and waist
      hip ratio were determined as surrogate measures of health. RESULTS: None of the
      participants achieved the recommended 60 minutes of daily moderate-to-vigorous
      physical activity (MVPA) on all 5 days. Significantly more time was spent
      engaging in sedentary activity compared with MVPA on both weekdays and weekends.
      MVPA and sedentary time were positively associated on weekdays after controlling
      for gender (P < .001). Weekday MVPA was positively associated with waist
      circumference (P < .001) and waist-hip ratio (P < .001). CONCLUSION: Singaporean
      adolescents fall substantially short of meeting the daily PA recommendations.
      Separate strategies to promote PA may be necessary for adolescents of differing
      weight status and gender. Pragmatic rather than idealistic targets to promote PA
      need to be set based on population-specific baseline data.

PMID- 25393420
TI  - Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in
      patients with interstitial lung disease.
AB  - BACKGROUND: Human telomere disease consists of a wide spectrum of disorders,
      including pulmonary, hepatic, and bone marrow abnormalities. The extent of bone
      marrow and liver abnormalities in patients with interstitial lung disease (ILD)
      and short telomeres is unknown. METHODS: The lung transplant clinic established a
      prospective protocol to identify short telomeres in patients with ILD not related
      to connective tissue disease or sarcoidosis. Patients with short telomeres
      underwent bone marrow biopsies, liver biopsies, or both as part of the evaluation
      for transplant candidacy. RESULTS: One hundred twenty-seven patients met ILD
      categorization for inclusion. Thirty were suspected to have short telomeres, and
      15 had the diagnosis confirmed. Eight of 13 (53%) patients had bone marrow
      abnormalities. Four patients had hypocellular marrow associated with macrocytosis
      and relatively normal blood counts, which resulted in changes to planned
      immunosuppression at the time of transplant. Four patients with more severe
      hematologic abnormalities were not listed because of myelodysplastic syndrome
      (two); monoclonal gammopathy of unclear significance (one); and hypocellular
      marrow, decreased megakaryocyte lineage associated with thrombocytopenia (one).
      Seven patients underwent liver biopsies, and six had abnormal liver pathology.
      These abnormalities did not affect listing for lung transplant, and liver
      biopsies are no longer routinely obtained. CONCLUSIONS: Subclinical bone marrow
      and liver abnormalities can be seen in patients with ILD and short telomeres, in
      some cases in the absence of clinically significant abnormalities in peripheral
      blood counts and liver function tests. A larger study examining the implication
      of these findings on the outcome of patients with ILD and short telomeres is
      needed.

PMID- 25393421
TI  - Computed tomographic measurement of airway remodeling and emphysema in advanced
      chronic obstructive pulmonary disease. Correlation with pulmonary hypertension.
AB  - RATIONALE: Pulmonary hypertension (PH) is an established complication of advanced
      chronic obstructive pulmonary disease (COPD) associated with increased mortality.
      The mechanisms coupling PH and bronchial obstruction are unknown; in particular,
      PH appears to be unrelated to emphysema. We hypothesized that computed
      tomographic (CT) measurement of airway remodeling instead of emphysema may
      correlate with PH in COPD. OBJECTIVES: We aimed to describe the clinical and CT
      characteristics of patients with COPD with or without PH and to correlate CT
      measurements of airway remodeling and emphysema with PH. METHODS: Data were
      retrieved from 60 COPD patients who underwent both right heart catheterization
      and computed tomography in a period of stability and had no other disease known
      to cause PH. CT measurement of airway wall thickness (WT-Pi10) was used to assess
      airway remodeling and low lung area percentage (LAA%) to quantify emphysema
      extent. MEASUREMENTS AND MAIN RESULTS: Thirty-four of the sixty patients with
      COPD had PH (mean pulmonary arterial pressure [PAPm] >= 25 mm Hg). There was no
      difference between the two groups regarding age, sex, and spirometric results,
      whereas there was more profound hypoxemia in the PH group. WT-Pi10 was increased
      in the patients with COPD and PH and correlated with PAPm (rho = 0.62; P <
      0.001). Conversely, there was no difference or correlation between PAPm and LAA%
      (rho = 0.12; P = 0.33). In multivariate analysis (R(2) = 0.53), WT-Pi10 was the
      independent predictor most associated with PAPm elevation, as compared to hypoxia
      (PaO2) or pulmonary arterial enlargement (diameter ratio between the pulmonary
      arterial truncus and the ascending aorta). CONCLUSIONS: This study demonstrates,
      for the first time to our knowledge, an association between structural
      alterations of bronchi and PH in COPD. Unlike quantification of emphysema, CT
      measurement of airway remodeling correlates with PAPm and could be used to
      estimate the severity of PH in COPD. Airway remodeling burden is not limited to
      airflow limitation in the assessment of COPD severity and mortality.

PMID- 25393422
TI  - How to get published in groundwater.

PMID- 25393423
TI  - Single-layer MnO2 nanosheets suppressed fluorescence of 7-hydroxycoumarin:
      mechanistic study and application for sensitive sensing of ascorbic acid in vivo.
AB  - In this study, we systematically investigate the mechanism of single-layer MnO2
      nanosheets suppressing fluorescence of 7-hydroxycoumarin and, based on this,
      demonstrate a new fluorescent method for in vivo sensing of ascorbic acid (AA) in
      rat brain. The mechanism for the fluorescence suppression is attributed to a
      combination of inner filter effect (IFE) and static quenching effect (SQE), which
      is different from those reported for the traditional two-dimensional nanosheets,
      and Forster resonant energy transfer (FRET) mechanism reported for MnO2
      nanosheets. The combination of IFE and SQE leads to an exponential decay in
      fluorescence intensity of 7-hydroxycoumarin with increasing concentration of MnO2
      nanosheets in solution. Such a property allows optimization of the concentration
      of MnO2 nanosheets in such a way that the addition of reductive analyte (e.g.,
      AA) will to the greatest extent restore the MnO2 nanosheets-suppressed
      fluorescence of 7-hydroxycoumarin through the redox reaction between AA and MnO2
      nanosheets. On the basis of this feature, we demonstrate a fluorescent method for
      in vivo sensing of AA in the cerebral systems with an improved sensitivity.
      Compared with the turn-on fluorescent method through first decreasing the
      fluorescence to the lowest level by adding concentrated MnO2 nanosheets, the
      method demonstrated here possesses a higher sensitivity, lower limit of
      detection, and wider linear range. Upon the use of ascorbate oxidase to achieve
      the selectivity for AA, the turn-on fluorescence method demonstrated here can be
      used for in vivo sensing of AA in a simple but reliable way. 

PMID- 25393424
TI  - Opinions of dentists on the barriers in providing oral health care to community
      dwelling frail older people: a questionnaire survey.
AB  - OBJECTIVE: The aim of this study was to investigate to what extent dentists in
      the Netherlands experience barriers in providing oral health care to community
      dwelling older people. BACKGROUND: As most publications on the barriers in
      providing oral health care to older people consist of surveys on oral health care
      in care homes, it was decided to investigate the barriers dentists experience in
      their own dental practices while providing oral health care to community-dwelling
      frail older people. MATERIAL AND METHODS: A representative sample of 1592 of the
      approximately 8000 dentists in the Netherlands aged 64 or younger were invited to
      respond to a questionnaire online. The dentists were asked to respond to 15
      opinions concerning oral healthcare provision to community-dwelling frail older
      people aged 75 years or more who experience problems in physical, psychological
      and social areas, as well as possible financial problems. RESULTS: The total
      response rate was 37% (n = 595; male=76%; average age 49). The majority of those
      who responded agreed that the reimbursement of oral health care to older people
      is poor. Two thirds of those who responded (66%) agreed that there are limited
      opportunities to refer the frail and elderly with complex oral healthcare
      problems to a colleague with specific knowledge and skills. CONCLUSION: Dentists
      experienced barriers in two domains; a lack of knowledge and practical
      circumstances. It was concluded that the dentist's gender, age, year of
      graduation and the number of patients aged 75 years or more treated weekly were
      in some respect, related to the barriers encountered.

PMID- 25393425
TI  - S-allyl cysteine activates the Nrf2-dependent antioxidant response and protects
      neurons against ischemic injury in vitro and in vivo.
AB  - Stroke is a devastating clinical condition for which an effective neuroprotective
      treatment is currently unavailable. S-allyl cysteine (SAC), the most abundant
      organosulfur compound in aged garlic extract, has been reported to possess
      neuroprotective effects against stroke. However, the mechanisms underlying its
      beneficial effects remain poorly defined. The present study tests the hypothesis
      that SAC attenuates ischemic neuronal injury by activating the nuclear factor
      erythroid-2-related factor 2 (Nrf2)-dependent antioxidant response in both in
      vitro and in vivo models. Our findings demonstrate that SAC treatment resulted in
      an increase in Nrf2 protein levels and subsequent activation of antioxidant
      response element pathway genes in primary cultured neurons and mice. Exposure of
      primary neurons to SAC provided protection against oxygen and glucose deprivation
      induced oxidative insults. In wild-type (Nrf2(+/+) ) mice, systemic
      administration of SAC attenuated middle cerebral artery occlusion-induced
      ischemic damage, a protective effect not observed in Nrf2 knockout (Nrf2(-/-) )
      mice. Taken together, these findings provide the first evidence that activation
      of the Nrf2 antioxidant response by SAC is strongly associated with its
      neuroprotective effects against experimental stroke and suggest that targeting
      the Nrf2 pathway may provide therapeutic benefit for the treatment of stroke. The
      transcription factor Nrf2 is involved in cerebral ischemic disease and may be a
      promising target for the treatment of stroke. We provide novel evidence that SAC
      confers neuroprotection against ischemic stroke by activating the antioxidant
      Nrf2 signaling pathway. ARE, antioxidant response element; GCLC, glutathione
      cysteine ligase regulatory subunit; GCLM, glutathione cysteine ligase modulatory
      subunit; HO-1, heme oxygenase-1; JNK, c-Jun N-terminal kinase; Keap1, Kelch-like
      ECH-associated protein 1; Maf, musculoaponeurotic fibrosarcoma; Nrf2, nuclear
      factor erythroid-2-related factor 2; SAC, S-allyl cysteine; ROS, reactive oxygen
      species. 

PMID- 25393426
TI  - FD&C Yellow No. 5 (tartrazine) degradation via reactive oxygen species triggered
      by TiO2 and Au/TiO2 nanoparticles exposed to simulated sunlight.
AB  - When exposed to light, TiO2 nanoparticles (NPs) become photoactivated and create
      electron/hole pairs as well as reactive oxygen species (ROS). We examined the ROS
      production and degradation of a widely used azo dye, FD&C Yellow No. 5
      (tartrazine), triggered by photoactivated TiO2 NPs. Degradation was found to
      follow pseudo-first order reaction kinetics where the rate constant increased
      with TiO2 NP concentration. Depositing Au on the surface of TiO2 largely enhanced
      electron transfer and ROS generation, which consequently accelerated dye
      degradation. Alkaline conditions promoted ROS generation and dye degradation.
      Results from electron spin resonance spin-trap spectroscopy suggested that at pH
      7.4, both hydroxyl radical (*OH) and singlet oxygen ((1)O2) were responsible for
      dye discoloration, whereas at pH 5, the consumption of (1)O2 became dominant.
      Implications for dye degradation in foods and other consumer products that
      contain both TiO2 and FD&C Yellow No. 5 as ingredients are discussed. 

PMID- 25393428
TI  - Defective nitric oxide metabolism in sickle cell disease.

PMID- 25393427
TI  - Ethanol negatively regulates hepatic differentiation of hESC by inhibition of the
      MAPK/ERK signaling pathway in vitro.
AB  - BACKGROUND: Alcohol insult triggers complex events in the liver, promoting
      fibrogenic/inflammatory signals and in more advanced cases, aberrant matrix
      deposition. It is well accepted that the regenerative capacity of the adult liver
      is impaired during alcohol injury. The liver progenitor/stem cells have been
      shown to play an important role in liver regeneration -in response to various
      chronic injuries; however, the effects of alcohol on stem cell differentiation in
      the liver are not well understood. METHODS: We employed hepatic progenitor cells
      derived from hESCs to study the impact of ethanol on hepatocyte differentiation
      by exposure of these progenitor cells to ethanol during hepatocyte
      differentiation. RESULTS: We found that ethanol negatively regulated hepatic
      differentiation of hESC-derived hepatic progenitor cells in a dose-dependent
      manner. There was also a moderate cell cycle arrest at G1/S checkpoint in the
      ethanol treated cells, which is associated with a reduced level of cyclin D1 in
      these cells. Ethanol treatment specifically inhibited the activation of the ERK
      but not JNK nor the p38 MAP signaling pathway. At the same time, the WNT
      signaling pathway was also reduced in the cells exposed to ethanol. Upon
      evaluating the effects of the inhibitors of these two signaling pathways, we
      determined that the Erk inhibitor replicated the effects of ethanol on the
      hepatocyte differentiation and attenuated the WNT/beta-catenin signaling,
      however, inhibitors of WNT only partially replicated the effects of ethanol on
      the hepatocyte differentiation. CONCLUSION: Our results demonstrated that ethanol
      negatively regulated hepatic differentiation of hESC-derived hepatic progenitors
      through inhibiting the MAPK/ERK signaling pathway, and subsequently attenuating
      the WNT signaling pathway. Thus, our finding provides a novel insight into the
      mechanism by which alcohol regulates cell fate selection of hESC-derived hepatic
      progenitor cells, and the identified pathways may provide therapeutic targets
      aimed at promoting liver repair and regeneration during alcoholic injury.

PMID- 25393429
TI  - Isolation and Genetic Characterization of Toxoplasma gondii from Black Bears
      (Ursus americanus), Bobcats (Lynx rufus), and Feral Cats (Felis catus) from
      Pennsylvania.
AB  - Toxoplasma gondii infects virtually all warm-blooded hosts worldwide. Recently,
      attention has been focused on the genetic diversity of the parasite to explain
      its pathogenicity in different hosts. It has been hypothesized that interaction
      between feral and domestic cycles of T. gondii may increase unusual genotypes in
      domestic cats and facilitate transmission of potentially more pathogenic
      genotypes to humans, domestic animals, and wildlife. In the present study, we
      tested black bear (Ursus americanus), bobcat (Lynx rufus), and feral cat (Felis
      catus) from the state of Pennsylvania for T. gondii infection. Antibodies to T.
      gondii were found in 32 (84.2%) of 38 bears, both bobcats, and 2 of 3 feral cats
      tested by the modified agglutination test (cut off titer 1:25). Hearts from
      seropositive animals were bioassayed in mice, and viable T. gondii was isolated
      from 3 of 32 bears, 2 of 2 bobcats, and 2 of 3 feral cats. DNA isolated from
      culture-derived tachyzoites of these isolates was characterized using multilocus
      PCR-RFLP markers. Three genotypes were revealed, including ToxoDB PCR-RFLP
      genotype #1 or #3 (Type II, 1 isolate), #5 (Type 12, 3 isolates), and #216 (3
      isolates), adding to the evidence of genetic diversity of T. gondii in wildlife
      in Pennsylvania. Pathogenicity of 3 T. gondii isolates (all #216, 1 from bear,
      and 2 from feral cat) was determined in outbred Swiss Webster mice; all three
      were virulent causing 100% mortality. Results indicated that highly mouse
      pathogenic strains of T. gondii are circulating in wildlife, and these strains
      may pose risk to infect human through consuming of game meat.

PMID- 25393430
TI  - Spherical colloidal photonic crystals.
AB  - CONSPECTUS: Colloidal photonic crystals (PhCs), periodically arranged
      monodisperse nanoparticles, have emerged as one of the most promising materials
      for light manipulation because of their photonic band gaps (PBGs), which affect
      photons in a manner similar to the effect of semiconductor energy band gaps on
      electrons. The PBGs arise due to the periodic modulation of the refractive index
      between the building nanoparticles and the surrounding medium in space with
      subwavelength period. This leads to light with certain wavelengths or frequencies
      located in the PBG being prohibited from propagating. Because of this special
      property, the fabrication and application of colloidal PhCs have attracted
      increasing interest from researchers. The most simple and economical method for
      fabrication of colloidal PhCs is the bottom-up approach of nanoparticle self
      assembly. Common colloidal PhCs from this approach in nature are gem opals, which
      are made from the ordered assembly and deposition of spherical silica
      nanoparticles after years of siliceous sedimentation and compression. Besides
      naturally occurring opals, a variety of manmade colloidal PhCs with thin film or
      bulk morphology have also been developed. In principle, because of the effect of
      Bragg diffraction, these PhC materials show different structural colors when
      observed from different angles, resulting in brilliant colors and important
      applications. However, this angle dependence is disadvantageous for the
      construction of some optical materials and devices in which wide viewing angles
      are desired. Recently, a series of colloidal PhC materials with spherical
      macroscopic morphology have been created. Because of their spherical symmetry,
      the PBGs of spherical colloidal PhCs are independent of rotation under
      illumination of the surface at a fixed incident angle of the light, broadening
      the perspective of their applications. Based on droplet templates containing
      colloidal nanoparticles, these spherical colloidal PhCs can be generated by
      evaporation-induced nanoparticle crystallization or polymerization of ordered
      nanoparticle crystallization arrays. In particular, because microfluidics was
      used for the generation of the droplet templates, the development of spherical
      colloidal PhCs has progressed significantly. These new strategies not only ensure
      monodispersity, but also increase the structural and functional diversity of the
      PhC beads, paving the way for the development of advanced optoelectronic devices.
      In this Account, we present the research progress on spherical colloidal PhCs,
      including their design, preparation, and potential applications. We outline
      various types of spherical colloidal PhCs, such as close-packed, non-close
      packed, inverse opal, biphasic or multiphasic Janus structured, and core-shell
      structured geometries. Based on their unique optical properties, applications of
      the spherical colloidal PhCs for displays, sensors, barcodes, and cell culture
      microcarriers are presented. Future developments of the spherical colloidal PhC
      materials are also envisioned.

PMID- 25393432
TI  - Graph-based unsupervised segmentation algorithm for cultured neuronal networks'
      structure characterization and modeling.
AB  - Large scale phase-contrast images taken at high resolution through the life of a
      cultured neuronal network are analyzed by a graph-based unsupervised segmentation
      algorithm with a very low computational cost, scaling linearly with the image
      size. The processing automatically retrieves the whole network structure, an
      object whose mathematical representation is a matrix in which nodes are
      identified neurons or neurons' clusters, and links are the reconstructed
      connections between them. The algorithm is also able to extract any other
      relevant morphological information characterizing neurons and neurites. More
      importantly, and at variance with other segmentation methods that require
      fluorescence imaging from immunocytochemistry techniques, our non invasive
      measures entitle us to perform a longitudinal analysis during the maturation of a
      single culture. Such an analysis furnishes the way of individuating the main
      physical processes underlying the self-organization of the neurons' ensemble into
      a complex network, and drives the formulation of a phenomenological model yet
      able to describe qualitatively the overall scenario observed during the culture
      growth.

PMID- 25393433
TI  - [Cornea: endothelial dystrophies and degenerations].

PMID- 25393434
TI  - [Degenerative maculopathy (in younger patients)].

PMID- 25393435
TI  - [Unusual IOL Calcification following Vitreoretinal Surgery with Silicone Oil
      Endotamponade].
AB  - PURPOSE: Calcification of intraocular lenses (IOL), although nowadays less
      frequent than in the past, is a well-documented complication that can still
      necessitate their explantation. Although mostly noted in hydrophilic materials it
      has been rarely reported in hydrophobic intraocular lenses. We wish to report on
      two unusual cases of intraocular lense (one hydrophobic and one hydrophilic with
      hydrophobic surface) calcification following vitrectomy and silicon oil
      endotamponade. METHODS: In the course of treatment both patients underwent
      multiple ocular interventions due to re-detachment/persistent macular hole
      including local rt-PA or triamcinolone injection due to persistent postoperative
      anterior chamber inflammation/macular oedema. Finally and after thorough patient
      examination with characteristic visual complaints and difficulty in the retinal
      assessment the extraction of the calcified lenses was considered necessary. The
      configuration as well as the elemental analysis of the opacified surface of the
      IOLs was performed by means of high magnification microscopy, scanning electron
      microscopy and energy dispersive X-ray spectroscopy (EDX). Intraocular and
      systemic histories of both patients were summarised. RESULTS: The scanning
      electron microscopy and EDX analysis demonstrated massive calcium-based deposits
      on the surface of the hydrophilic and a diffuse vacuolation and calcification
      consisting of oxygen (O), silicon (Si), magnesium (Mg), aluminium (Al), sulphur
      (S) and phosphorus (P) on the surface of the hydrophobic IOL. CONCLUSION: The
      explantation of an IOL due to calcification represents an unusual event. The
      careful consideration of systemic and ocular factors that promote calcification
      processes can help reduce the incidence of calcification. Despite all efforts in
      material production and risk factor analysis, it is not always possible to define
      or even predict the exact cause of this phenomenon and in the presence of
      corresponding clinical symptoms IOL exchange remains as the sole option.

PMID- 25393436
TI  - [Glaucoma filtering surgery in the elderly over eighty years old: an analysis of
      postoperative risks].
AB  - BACKGROUND: Aim of this retrospective study was to identify the postoperative
      complications following trabeculectomy with mitomycin C in patients aged 80 years
      or older at the time of surgery. Additionally, the corresponding risk factors for
      postoperative complications were analysed. MATERIAL AND METHODS: During a defined
      period between 2005 and 2009 all trabeculectomies in this age group at the
      Department of Ophthalmology, University of Cologne were identified. Second eye
      surgery and re-trabeculectomies in the same eye were excluded from data
      collection. Postoperative ocular hypotony (< 6 mmHg) and hypertony (> 20 mmHg),
      bleeding, corneal erosion, re-surgery and prolonged postoperative duration of
      hospital stay were defined as complications. RESULTS: One hundred and twenty eyes
      of 120 patients were included. The mean age was 83.4 years, 62.5 % patients were
      female. Eighty nine percent of the eyes were pseudophakic, the mean visual field
      defect was - 17.3 dB, the mean preoperative intraocular pressure under pressure
      reducing medication was 24.1 mmHg. Considering the perioperative complications
      there was no significant difference depending on the age (80-85 years, n = 79 and
      > 85 years, n = 41), depending on the type of anesthesia (general, n = 80 and
      local, n = 40) or depending on antiplatelet (APT)/anticoagulative (ACT) therapy
      (APT, n = 55 and ACT, n = 16). The postoperative duration of the hospital stay
      showed significant correlations with the occurrence of corneal erosions,
      postoperative ocular hypertony, loss of anterior chamber and choroidal
      detachment. CONCLUSIONS: The postoperative risks of antiglaucomatous filtering
      surgery did not increase with age or comorbidity. However, even minor
      perioperative complications had direct implications on the duration of the
      hospital stay.

PMID- 25393437
TI  - [Surgical treatment of neovascular glaucoma].
AB  - PURPOSE: The neovascular glaucoma is one of the leading causes for an
      enucleation. The cyclocryocoagulation, the peripheral retinal cryocoagulation and
      the intravitreal injection of bevacizumab as combined therapy aim at the
      reduction of the intraocular pressure and of neovascularisation. MATERIALS AND
      METHODS: This study follows up 135 patients with neovascular glaucoma who
      underwent the above-mentioned combined therapy consisting of
      cyclocryocoagulation, peripheral retinal cryocoagulation and intravitreal
      injection of bevacizumab. RESULTS: The most common causes of neovascular glaucoma
      in our study are diabetic retinopathy and central retinal vein occlusion. The
      intraocular pressure was 37.4 mmHg (+/- 15.8) mmHg preoperatively under maximum
      antiglaucomatous therapy and was reduced to 19.0 (+/- 8.5) mmHg direct
      postoperatively. In the long-term intraocular pressure remained within the normal
      range in 93.33 % of patients. A successful reduction of the local
      antiglaucomatous drops of 1.9 substances to 1.7 substances was observed after 3
      months. The oral intake of acetazolamide was also statistically significantly
      reduced. 47.37 % of the patients were normotensive without local therapy and only
      3 patients were still on acetazolamide even after 1 year. The most serious
      complication was a phthisis bulbi in 1.5 % of patients. Overall 98.5 % of
      patients remained free of pain and maintained visual acuity after the end of the
      follow-up. CONCLUSION: Long-term pressure regulation and freedom from pain were
      successfully achieved. For decompensated neovascular glaucoma with poor vision
      and painful bulb, the combination of retinal cryocoagulation and intravitreal
      application of bevacizumab is an important therapeutic option.

PMID- 25393438
TI  - [Follow-up of postoperative endophthalmitis after cataract surgery and
      intravitreal injection of drugs - an analysis since 2009].
AB  - BACKGROUND: The frequency of intravitreal injection of drugs (IVI) has
      significantly increased recently and it is performed like cataract surgery as an
      outpatient procedure. The occurrence of postoperative endophthalmitis is rare,
      only few data of multicentre studies are available. METHODS: We analysed the data
      of 30 consecutive patients with endophthalmitis following cataract surgery (group
      1, n = 20) and IVI (group 2, n = 10) requiring therapy in a referral eye clinic
      from January 2009 to December 2013. All patients received topical and systemic
      anti-inflammatory and anti-infective therapy. Due to vitreous opacification and
      severe loss of vision 83 % of the eyes underwent immediately pars plana
      vitrectomy with diagnostic microbiological probe and intravitreal application of
      vancomycin and gentamicin. RESULTS: Endophthalmitis occurred independently in
      both groups 1 to 10 days, on average 4 days, postoperatively. Group 1 showed
      conjunctival infection in 80 % (n = 16), group 2 in 20 % (n = 2). Hypopyon was
      found in group 1 in 65 % (n = 13), in group 2 in 40 % (n = 4). Group 1 presented
      retinal haemorrhages and epiretinal fibrin membranes in 15 % (n = 3), group 2 in
      70 % (n = 7). Vitreous cultures were positive in 80 % (vancomycin-sensitive
      staphylococci). Staphylococcus was the most frequent bacteria, resistant to
      ceftazidime. In group 1 visual acuity was initially in 65 % (n = 13) of the eyes
      < 20/400 or worse, in group 2 90 % (n = 9) of the eyes had hand motions and in 10
      % (n = 1) worse than 20/400. Visual outcome was 20/30 on average for group 1, PVR
      retinal detachment occurred once. In group 2 no patient achieved better visual
      outcome than < 20/400, 40 % of the eyes required permanent silicon oil tamponade
      because of PVR retinal detachment. The major pathogens were staphylococci
      resistant to ceftazidim. CONCLUSION: Endophthalmitis following IVI had poor
      visual outcome compared to endophthalmitis following cataract surgery and showed
      less anterior segment symptoms.

PMID- 25393439
TI  - [Surgical managment of retinal detachment].
AB  - The detachment of the neurosensory retina from the underlying retinal pigment
      epithelium can be related to breaks of the retina allowing vitreous fluid to gain
      access to the subretinal space, to exudative changes of the choroid such as
      tumours or inflammatory diseases or to excessive tractional forces exerted by
      interactions of the collagenous vitreous and the retina. Tractional retinal
      detachment is usually treated by vitrectomy and exudative detachment can be
      addressed by treatment of the underlying condition in many cases. In
      rhegmatogenous retinal detachment two different surgical procedures, vitrectomy
      and scleral buckling, can be applied for functional and anatomic rehabilitation
      of our patients. The choice of the surgical procedure is not really standardised
      and often depends on the experience of the surgeon and other more ocular factors
      including lens status, the number of retinal breaks, the extent of the detachment
      and the amount of preexisting PVR. Using both techniques, anatomic success rates
      of over 90 % can be achieved. Especially in young phakic patients scleral
      buckling offers the true advantage to prevent the progression of cataract
      formation requiring cataract extraction and intraocular lens implantation.
      Therefore, scleral buckling should be considered in selected cases as an
      alternative surgical option in spite of the very important technical refinements
      in modern vitrectomy techniques. 

PMID- 25393440
TI  - [Basic in vitro studies on VEGF inhibition with aflibercept: similarities and
      differences to other VEGF-binding therapeutic proteins].
AB  - Patients suffering from various retinal diseases benefit from therapies directed
      against the vascular endothelial growth factor (VEGF). Aflibercept (Eylea) is
      another VEGF-binding protein available for intravitreal injection, in addition to
      the antibody bevacizumab (Avastin) and the F(ab) fragment ranibizumab (Lucentis).
      Aflibercept's distinct structure and broader binding specificity may have
      clinically relevant consequences, which is supported by basic in vitro studies
      and observations in animal eyes. All pathological processes involving
      neovascularisation are driven by the dominant action of VEGF, but other factors
      including placenta growth factor (PlGF), a mitogenic protein for retinal
      endothelial cells, potentially modulate its effects. Aflibercept is an inhibitor
      of both VEGF and PlGF and therefore may have superior therapeutic effects in some
      cases. However, whether or not aflibercept's broader binding specificity or
      different affinities for the different VEGF-binding proteins to VEGF result in
      substantially diverse therapeutic efficiencies has not yet been clarified. In
      vitro studies confirm that aflibercept efficiently prevents or normalises VEGF
      stimulation of retinal cells and disturbance of their barrier function. These
      experiments also show that aflibercept is taken up by important retinal cell
      types and affects their normal function, i.e., migration of endothelial cells and
      phagocytosis of pigment epithelial cells. In accordance with a role of the Fc
      domains of aflibercept and bevacizumab, substantial amounts of both proteins are
      internalised, whereas only a small portion of ranibizumab enters the cells.
      Internalisation and storage by ocular cells, also observed in vivo after
      intravitreal injection into eyes of monkeys, may result in not yet recognised
      side effects during long-term treatment of patients with certain VEGF-binding
      proteins. 

PMID- 25393441
TI  - Clinical evaluation of acoustic respiration rate monitoring compared with
      conventional systems in the postanaesthesia care unit.

PMID- 25393442
TI  - Health Care Coverage Decision Making in Low- and Middle-Income Countries:
      Experiences from 25 Coverage Schemes.
AB  - Lessons learned by countries that have successfully implemented coverage schemes
      for health services may be valuable for other countries, especially low- and
      middle-income countries (LMICs), which likewise are seeking to provide/expand
      coverage. The research team surveyed experts in population health management from
      LMICs for information on characteristics of health care coverage schemes and
      factors that influenced decision-making processes. The level of coverage provided
      by the different schemes varied. Nearly all the health care coverage schemes
      involved various representatives and stakeholders in their decision-making
      processes. Maternal and child health, cardiovascular diseases, cancer, and HIV
      were among the highest priorities guiding coverage development decisions.
      Evidence used to inform coverage decisions included medical literature, regional
      and global epidemiology, and coverage policies of other coverage schemes. Funding
      was the most commonly reported reason for restricting coverage. This exploratory
      study provides an overview of health care coverage schemes from participating
      LMICs and contributes to the scarce evidence base on coverage decision making.
      Sharing knowledge and experiences among LMICs can support efforts to establish
      systems for accessible, affordable, and equitable health care.

PMID- 25393443
TI  - Respiratory Tract Deposition of Inhaled Wood Smoke Particles in Healthy
      Volunteers.
AB  - BACKGROUND: Respiratory tract deposition of air pollution particles is a key to
      their adverse health effects. This study was aimed to determine the size-resolved
      deposition fraction (DF) of sooty wood smoke particles in the lungs of healthy
      subjects. The type of wood smoke investigated is typical for household air
      pollution from solid fuels, which is among the largest environmental health
      problems globally. METHODS: Twelve healthy volunteers inhaled diluted wood smoke
      from incomplete soot-rich combustion in a common wood stove. The DF of smoke
      particles (10-500 nm) was measured during three 15-min exposures in each subject
      during spontaneous breathing. Lung function was measured using standard
      spirometry. RESULTS: The total DFs by particle number concentration were 0.34+/
      0.08. This can be compared with DFs of 0.21-0.23 in healthy subjects during
      previous experiments with wood pellet combustion. For particle mass, the total
      DFs found in this study were 0.22+/-0.06. DF and breathing frequency were
      negatively correlated as expected from model calculations (p<0.01). CONCLUSIONS:
      The DF of the investigated sooty wood smoke particles was higher than for
      previously investigated particles generated during more efficient combustion of
      biomass. Together with toxicological studies, which have indicated that
      incomplete biomass combustion particles rich in soot and polycyclic aromatic
      hydrocarbons (PAHs) are especially harmful, these data highlight the health risks
      of inadequate wood combustion.

PMID- 25393450
TI  - Hydrocarbons preserved in a ~2.7 Ga outcrop sample from the Fortescue Group,
      Pilbara Craton, Western Australia.
AB  - The hydrocarbons preserved in an Archean rock were extracted, and their
      composition and distribution in consecutive slices from the outside to the inside
      of the rock were examined. The 2.7 Ga rock was collected from the Fortescue Group
      in the Pilbara region, Western Australia. The bitumen I (solvent-extracted rock)
      and bitumen II (solvent-extracted hydrochloric acid-treated rock) fractions have
      different hydrocarbon compositions. Bitumen I contains only trace amounts of
      aliphatic hydrocarbons and virtually no aromatic hydrocarbons. In contrast,
      bitumen II contains abundant aliphatic and aromatic hydrocarbons. The difference
      seems to reflect the weathering history and preservational environment of the
      investigated rock. Aliphatic hydrocarbons in bitumen I are considered to be
      mainly from later hydrocarbon inputs, after initial deposition and burial, and
      are therefore not indigenous. The lack of aromatic hydrocarbons in bitumen I
      suggests a severe weathering environment since uplift and exposure of the rock at
      the Earth's surface in the Cenozoic. On the other hand, the high abundance of
      aromatic hydrocarbons in bitumen II suggests that bitumen II hydrocarbons have
      been physically isolated from removal by their encapsulation within carbonate
      minerals. The richness of aromatic hydrocarbons and the relative scarcity of
      aliphatic hydrocarbons may reflect the original compositions of organic materials
      biosynthesised in ancient organisms in the Archean era, or the high thermal
      maturity of the rock. Cyanobacterial biomarkers were observed in the surficial
      slices of the rock, which may indicate that endolithic cyanobacteria inhabited
      the surface outcrop. The distribution of aliphatic and aromatic hydrocarbons
      implies a high thermal maturity, which is consistent with the lack of any
      specific biomarkers, such as hopanes and steranes, and the prehnite-pumpellyite
      facies metamorphic grade.

PMID- 25393452
TI  - Effectiveness of mitigation measures in reducing future primary particulate
      matter emissions from on-road vehicle exhaust.
AB  - This work evaluates the effectiveness of on-road primary particulate matter
      emission reductions that can be achieved by long-term vehicle scrappage and
      retrofit measures on regional and global levels. Scenario analysis shows that
      scrappage can provide significant emission reductions as soon as the measures
      begin, whereas retrofit provides greater emission reductions in later years, when
      more advanced technologies become available in most regions. Reductions are
      compared with a baseline that already accounts for implementation of clean
      vehicle standards. The greatest global emission reductions from a scrappage
      program occur 5 to 10 years after its introduction and can reach as much as 70%.
      The greatest reductions with retrofit occur around 2030 and range from 16-31%.
      Monte Carlo simulations are used to evaluate how uncertainties in the composition
      of the vehicle fleet affect predicted reductions. Scrappage and retrofit reduce
      global emissions by 22-60% and 15-31%, respectively, within 95% confidence
      intervals, under a midrange scenario in the year 2030. The simulations provide
      guidance about which strategies are most effective for specific regions. Retrofit
      is preferable for high-income regions. For regions where early emission standards
      are in place, scrappage is suggested, followed by retrofit after more advanced
      emission standards are introduced. The early implementation of advanced emission
      standards is recommended for Western and Eastern Africa. 

PMID- 25393453
TI  - Circular random motion in diatom gliding under isotropic conditions.
AB  - How cells migrate has been investigated primarily for the case of trajectories
      composed by joined straight segments. In contrast, little is known when cellular
      motion follows intrinsically curved paths. Here, we use time-lapse optical
      microscopy and automated trajectory tracking to investigate how individual cells
      of the diatom Nitzschia communis glide across surfaces under isotropic
      environmental conditions. We find a distinct kind of random motion, where
      trajectories are formed by circular arcs traveled at constant speed, alternated
      with random stoppages, direction reversals and changes in the orientation of the
      arcs. Analysis of experimental and computer-simulated trajectories show that the
      circular random motion of diatom gliding is not optimized for long-distance
      travel but rather for recurrent coverage of limited surface area. These results
      suggest that one main biological role for this type of diatom motility is to
      efficiently build the foundation of algal biofilms. 

PMID- 25393451
TI  - Regulation and disregulation of mammalian nucleotide excision repair: a pathway
      to nongermline breast carcinogenesis.
AB  - Nucleotide excision repair (NER) is an important modulator of disease, especially
      in constitutive deficiencies such as the cancer predisposition syndrome Xeroderma
      pigmentosum. We have found profound variation in NER capacity among normal
      individuals, between cell-types and during carcinogenesis. NER is a repair system
      for many types of DNA damage, and therefore many types of genotoxic carcinogenic
      exposures, including ultraviolet light, products of organic combustion, metals
      and oxidative stress. Because NER is intimately related to cellular metabolism,
      requiring components of both the DNA replicative and transcription machinery, it
      has a narrow range of functional viability. Thus, genes in the NER pathway are
      expressed at the low levels manifested by, for example, nuclear transcription
      factors. As NER activity and gene expression vary by cell-type, it is inherently
      epigenetically regulated. Furthermore, this epigenetic modulation is disregulated
      during sporadic breast carcinogenesis. Loss of NER is one basis of genomic
      instability, a required element in cellular transformation, and one that
      potentially influences response to therapy. In this study, we demonstrate
      differences in NER capacity in eight adult mouse tissues, and place this result
      into the context of our previous work on mouse extraembryonic tissues, normal
      human tissues and sporadic early stage human breast cancer. 

PMID- 25393454
TI  - Pediatric Medical Care System in China Has Significantly Reduced Abandonment of
      Acute Lymphoblastic Leukemia Treatment.
AB  - In this study, we have analyzed both administrative and clinical data from our
      hospital during 2002 to 2012 to evaluate the influence of government medical
      policies on reducing abandonment treatment in pediatric patients with acute
      lymphoblastic leukemia. Two policies funding for the catastrophic diseases and
      the new rural cooperative medical care system (NRCMS) were initiated in 2005 and
      2011, respectively. About 1151 children diagnosed with acute lymphoblastic
      leukemia were enrolled in our study during this period and 316 cases abandoned
      treatment. Statistical differences in sex, age, number of children in the family,
      and family financial status were observed. Of most importance, the medical
      insurance coverage was critical for reducing abandonment treatment. However, 92
      cases abandoning treatment after relapse did not show significant difference
      either in medical insurance coverage or in duration from first complete
      remission. In conclusion, financial crisis was the main reason for abandoning
      treatment. Government-funded health care expenditure programs reduced families'
      economic burden and thereby reduced the abandonment rate with resultant increased
      overall survival. 

PMID- 25393455
TI  - Impaired endothelial function in patients with mild primary hyperparathyroidism
      improves after parathyroidectomy.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with cardiovascular
      morbidity; however, data on the reversibility of cardiovascular disease in mild
      primary hyperparathyroidism are conflicting. The aim of this study was to assess
      endothelial function in patients with mild PHPT before and after
      parathyroidectomy (Ptx). METHODS: We prospectively evaluated 53 patients with
      mild PHPT (Group 1; 45 women, eight men; aged 52 +/- 3.1 years) and 46 healthy
      control subjects (Group 2; 38 women, eight men; aged 46 +/- 9.5 years).
      Endothelial function was measured as flow-mediated dilation (FMD) and carotid
      intima-media thickness (CIMT) using Doppler ultrasonography. Patients with
      diabetes mellitus, coronary heart disease, impaired renal function,
      hyperthyroidism, hypothyroidism and a history of smoking were excluded from the
      study. Patients were studied at baseline and 6-12 months after the first
      evaluation. RESULTS: There were no differences with respect to age, gender and
      BMI between the two groups. Hypertension prevalence was three times higher in
      group 1 than in controls. % FMD was lower in group 1 than in group 2 (2.6 +/- 1.2
      vs 14.8 +/- 9.6, P < 0.001). CIMT was higher in patients with PHPT than controls
      (0.69 +/- 0.18 vs 0.61 +/- 0.12, P = 0.045). This significance remained when
      hypertensive patients were excluded from the analysis. While FMD and CIMT
      improved significantly after Ptx, there were no differences in mild PHPT patients
      who followed without parathyroidectomy. CONCLUSION: FMD and CIMT are impaired in
      patients with mild PHPT compared to controls and improved significantly after a
      successful Ptx. Ptx improves endothelial function in patients with mild PHPT that
      may lead to decreased cardiovascular morbidity and mortality.

PMID- 25393456
TI  - Learning curve for robot-assisted neck dissection in head and neck cancer: a 3
      year prospective case study and analysis.
AB  - IMPORTANCE: Robot-assisted neck dissection (RAND) for the management of regional
      metastases is a recently developed technique in the field of head and neck cancer
      that uses a robotic surgical system. This is the first report that estimates the
      learning curve for RAND. OBJECTIVES: To evaluate a learning curve for RAND
      according to the types of neck dissection and report clinical outcomes. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective case study of 90 patients undergoing neck
      dissection between May 2010 and April 2013 at a university tertiary referral
      center. INTERVENTIONS: Fifty modified radical neck dissections (MRNDs) and 40
      supraomohyoid neck dissections (SONDs) were performed by a single surgeon using a
      robotic surgical system to treat head and neck cancer. The MRND and the SOND
      groups were subdivided into 5 and 4 consecutive subgroups of 10 patients each,
      respectively. MAIN OUTCOMES AND MEASURES: Perioperative parameters were compared,
      including mean operation time, duration and amount of drainage, length of
      hospital stay, and postoperative complications. RESULTS: Significant decreases in
      mean operation time were observed as experience performing RAND increased in both
      the MRND and the SOND groups. The mean operation time for the MRND group
      decreased by 29% over the course of our study (initial subgroup, 298.1 minutes;
      last subgroup, 212.4 minutes). The mean operation time for the SOND group
      decreased by 53% over the course of our study (initial subgroup, 226.5 minutes;
      last subgroup, 106.1 minutes). There were no significant differences between
      subgroups for the other perioperative parameters. CONCLUSIONS AND RELEVANCE: We
      explored the RAND learning curve in a single institution over a 3-year period.
      This study can be used as a timeline reference for institutions where the RAND
      procedure will be adopted as an alternative procedure.

PMID- 25393457
TI  - Continuing aspirin therapy during percutaneous nephrolithotomy: unsafe or under
      utilized?
AB  - INTRODUCTION: Aspirin, as an inhibitor of platelets, is traditionally
      discontinued prior to percutaneous nephrolithotomy (PCNL) given the concern for
      increased surgical hemorrhage. However, this practice is based on expert opinion
      only, and mounting evidence suggests holding aspirin perioperatively can be more
      harmful than once thought. We sought to compared PCNL outcomes and complications
      in patients continuing aspirin to those stopping aspirin perioperatively.
      METHODS: A retrospective review was performed of 321 consecutive PCNLs done
      between July 2012 and March 2014. Patients were separated into two groups. The on
      aspirin group consisted of patients continuing aspirin throughout the
      perioperative period. The off-aspirin group had aspirin held temporarily pre- and
      postoperatively. Surgical outcomes and complications were compared between
      groups. RESULTS: Of the 321 PCNLs, 60 (18.7%) occurred in patients chronically
      taking aspirin. The on-aspirin group included 17 PCNLs (5.2%), while the off
      aspirin group included 43 PCNLs (13.4%). There were no differences between groups
      in terms of operative time (77 minutes vs 74 minutes, p=0.212), hemoglobin change
      (p=0.522), stone size (21 mm vs 22 mm, p=1.0), stone-free rate (p=0.314), median
      length of hospitalization (p=0.642), transfusion rate (p=0.703), or total
      complications (p=1.0). No patient experienced a thromboembolic event.
      CONCLUSIONS: PCNL is safe in patients continuing aspirin perioperatively and does
      not result in more blood transfusions, angioembolization procedures, or
      complications. Patients with large stone burdens who are at high risk for
      thromboembolic events appear to be able to safely undergo PCNL without
      discontinuing aspirin.

PMID- 25393458
TI  - Post-traumatic stress disorder in veterans.
AB  - Over 2000 general practice encounters per year (2.3%) in BEACH are with
      repatriation health card holders, referred to here as veterans. The patients are
      veterans of Australia's defence force or war widows, widowers or dependent
      children. We compared the rate at which post-traumatic stress disorder (PTSD) was
      managed among veterans and non-veterans from April 2009 to June 2014. 

PMID- 25393459
TI  - PTSD--an update for general practitioners.
AB  - BACKGROUND: Australians are commonly exposed to traumatic events, which can lead
      to the development of post-traumatic stress disorder (PTSD). Several recent
      developments in the trauma field have led to significant changes in how PTSD is
      diagnosed and treated. OBJECTIVE: This article provides up-to-date guidance for
      general practitioners (GPs) in the recognition of PTSD and the current best
      practice recommendations for pharmacological and psychological treatment.
      DISCUSSION: Often the first port-of-call, GPs are well placed to help patients
      who have recently experienced a potentially traumatic event and are at risk of
      developing PTSD. The role of the GP can include initial support, assessment,
      treatment and, where indicated, appropriate specialist referral. There are recent
      clinical practice guidelines that GPs can use to assess and determine appropriate
      treatment for their patients with PTSD.

PMID- 25393460
TI  - Traumatic brain injury--support for injured people and their carers.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a major cause of lifelong disability
      and death worldwide, but is considered a 'silent epidemic' as society is largely
      unaware of the magnitude of the problem. TBI is a complex injury with a broad
      spectrum of symptoms and disabilities. Patients with a TBI may have a range of
      physical, mental, cognitive and social problems. OBJECTIVE: This article provides
      a summary of the available evidence for assessing TBI and managing the common
      mental health, physical and cognitive/behavioural issues associated with TBI.
      DISCUSSION: Translational and clinical research has revealed that TBI can no
      longer be regarded as a single clinical entity with a defined outcome. Each type
      of injury can lead to a distinct clinical condition that requires careful
      assessment and appropriate management to reduce long-term disability. In this
      article we discuss some of the more common health issues related to TBI.

PMID- 25393461
TI  - Beyond resettlement: long-term care for people who have had refugee-like
      experiences.
AB  - BACKGROUND: Since 1945, more than 700 000 refugees and displaced persons,
      survivors of conflicts in over 60 countries, have resettled in Australia. Every
      general practitioner (GP) will have patients who have had refugee-like
      experiences. OBJECTIVE: To describe the health needs of survivors of war and
      conflict in the immediate and long-term resettlement periods. DISCUSSION: In the
      immediate post-settlement period, refugees and asylum seekers will need
      assessment, catch-up primary healthcare and, in some cases, psychological
      support. Although refugees are generally a resilient group, enhanced support may
      be needed over key life periods: childbirth, rearing of young children and
      entering frail age. Asylum seekers (who do not have permanent visas) often face
      structural impediments to healthcare access and may be unable to meet basic
      health needs; GPs need to be aware of the enhanced need for psychological safety
      in addition to catch-up healthcare in this population.

PMID- 25393462
TI  - Family violence across the life cycle.
AB  - BACKGROUND: Family violence covers a range of abuse including child abuse and
      neglect, intimate partner violence and elder abuse. Each form of abuse has a
      significant negative impact on health and wellbeing, and patients present to
      general practice with varying physical and psychological issues. General practice
      is unique in that it often works with an entire family, which can be challenging
      and needs to be actively managed. OBJECTIVE: This article aims to address
      clinical questions that general practitioners (GPs) may have in identifying and
      responding to patients experiencing family violence. It takes into account the
      different types of abuse victims experience and how to respond to perpetrators.
      The recommendations in this article can also apply to same-sex relationships.
      DISCUSSION: Managing family violence requires a whole-of-practice approach to
      encourage a safe environment in which families can dis-close abuse and where GPs
      can respond appropriately. Abuse can be inter-generational and GPs have a role in
      identification, management and referral.

PMID- 25393463
TI  - How to write a medico-legal report.
AB  - BACKGROUND: The preparation and provision of medico-legal reports by the treating
      doctor is an inevitable but sometimes unwelcome part of general practice.
      OBJECTIVE: This article outlines the steps involved in preparing a 'good' medico
      legal report, including some of the common pitfalls to avoid. DISCUSSION: General
      practitioners play an important role in providing medico-legal reports about
      their patients for a wide variety of purposes. A medico-legal report may be seen
      by a diverse, non-medical audience. Once prepared, the report may be used as
      evidence in court proceedings and subjected to close scrutiny. A structured and
      comprehensive medico-legal report may minimise the chances of having to give
      evidence in court.

PMID- 25393464
TI  - Decreased fetal movements: a practical approach in a primary care setting.
AB  - BACKGROUND: The association between perceived decreased fetal movement (DFM) and
      adverse outcomes in pregnancy is widely acknowledged. However, in the general
      practice setting, a common first point-of-call for pregnant women, guidelines for
      appropriate management of DFM are lacking. OBJECTIVE: This article reviews the
      current evidence surrounding women presenting with DFM and suggests appropriate
      management in the community setting and the indications for hospital referral.
      DISCUSSION: Maternal perception of DFM is a common reason for women to make
      contact with their healthcare provider. Women presenting on multiple occasions
      with DFM are at increased risk of poor perinatal outcomes, including fetal death,
      intrauterine fetal growth restriction (IUFGR) or preterm birth. An evaluation of
      women presenting with DFM should involve a thorough history, examination and
      auscultation of fetal heart, cardiotocography (CTG) and ultrasound if indicated.

PMID- 25393465
TI  - Missed diagnosis of Sturge-Weber syndrome: sequelae in adulthood.

PMID- 25393466
TI  - Cutaneous manifestation of visceral malignancy: a case study.

PMID- 25393467
TI  - Whitish nodules on the fingers.

PMID- 25393468
TI  - Approach to low back pain--exercise physiology.

PMID- 25393469
TI  - Diabetes clinic attendance improves diabetes management in an urban Aboriginal
      and Torres Strait Islander population.
AB  - BACKGROUND: Optimal diabetes management involves frequent monitoring and
      achievement of outcome targets. A primary care diabetes clinic that provides a
      'one-stop shop' may facilitate more regular review and improve patient care.
      METHODS: A retrospective clinical audit was conducted of adult patients with type
      2 diabetes, who attended an urban Aboriginal Community Controlled Health Service
      (ACCHS) in Canberra during 2012 (n = 65). Diabetes clinic attendees were compared
      with non-attendees for the proportion meeting guidelines targets from The Royal
      Australian College of General Practitioners. RESULTS: The average age of the
      patients was 56 years and 29% were smokers. There was a statistically significant
      difference between diabetes clinic attendees and non-attendees in meeting
      diabetes check guidelines, pneumococcal vaccination and use of hypo-glycaemic
      medication. Despite this difference, clinical outcomes between the two groups
      were not statistically different. DISCUSSION: A comprehensive diabetes clinic may
      improve management in the ACCHS setting. The clinic promotes regular checks and
      higher vaccination rates, although insufficient evidence exists to show that this
      translates to better clinical outcomes. This model may be transferrable to other
      primary care settings.

PMID- 25393470
TI  - A user assessment of the potential for shared medical appointments in Australia.
AB  - BACKGROUND: In some countries, shared medical appointments (SMAs) have been shown
      to be more effective than single consultations for managing chronic diseases. Our
      study was designed as the first stage of a Royal Australian College of General
      Practitioners (RACGP) funded project to assess potential patient and provider
      support for SMAs if they were to become available in Australia. METHODS: We
      conducted focus groups with healthcare providers and patients with diabetes in
      four large regional health centres in NSW. The data were analysed using rigorous
      qualitative processes. RESULTS: Healthcare provider participants appeared
      overwhelmingly in favour of SMAs, while patients were divided on the process.
      Where opposed, patients cited concerns about confidentiality and their
      satisfaction with the status quo. DISCUSSION: There appears to be a groundswell
      of interest in SMAs that warrants further investigation in the Australian
      healthcare system. Issues of reimbursement, homogeneity of groups and training
      need further consideration.

PMID- 25393471
TI  - GP supervisors--an investigation into their motivations and teaching activities.
AB  - BACKGROUND: There is little empirical information on how general practitioner
      (GP) supervisors teach and the reasons for the variation in their teaching
      methods. Could the variation be due to differing motivations to teach? METHODS:
      Supervisors from one regional training provider who attended educational
      workshops in 2013 were surveyed, seeking infor-mation on their motivation to
      become and remain a supervisor, and the frequency of use of selected teaching
      activities. RESULTS: The majority of respondents cited intrinsic motivators,
      including enjoying teaching (84%), contribution to the profession and community
      (82%), adding variety (78%) and workforce/succession planning (69%), as reasons
      for becoming GP supervisors. The expected relationships between motivations and
      teaching activities were not found. DISCUSSION: Variation in teaching activities
      used by supervisors does not appear to be associated with differing motivations.
      Measuring the use of teaching activities is not a mechanism to determine a
      supervisor's commitment to teaching.

PMID- 25393472
TI  - A novel mutation in the XPA gene results in two truncated protein variants and
      leads to a severe XP/neurological symptoms phenotype.
AB  - BACKGROUND: The nucleotide excision repair (NER) pathway repairs UV-induced DNA
      lesions in an accurate fashion and prevents UV-irradiated areas of the skin from
      tumour formation. The XPA protein plays a major role in DNA damage demarcation as
      well as stabilization of other NER factors and was found to be defective in
      xeroderma pigmentosum (XP) complementation group A patients. OBJECTIVE:
      Characterization of four new XP-A patients. METHODS: Genomic and cDNA sequencing,
      post-UV cell survival of living cells, host-cell reactivation of patients'
      fibroblasts and Western blotting. RESULTS: One of the four investigated patients
      shows a novel mutation leading to two different truncated protein variants. Three
      patients contain the already described p.R228X mutation. All patient cell lines
      exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases
      stable protein expression was detected. CONCLUSION: We discovered four new XP-A
      patients and a novel XPA mutation resulting in two diverse patient alleles.

PMID- 25393473
TI  - Zoledronic acid induces apoptosis and S-phase arrest in mesothelioma through
      inhibiting Rab family proteins and topoisomerase II actions.
AB  - Zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, produced anti-tumor
      effects through apoptosis induction or S-phase arrest depending on human
      mesothelioma cells tested. An addition of isoprenoid, geranylgeraniol but not
      farnesol, negated these ZOL-induced effects, indicating that the ZOL-mediated
      effects were attributable to depletion of geranylgeranyl pyrophosphates which
      were substrates for prenylation processes of small guanine-nucleotide-binding
      regulatory proteins (small G proteins). ZOL-treated cells decreased a ratio of
      membrane to cytoplasmic fractions in RhoA, Cdc42 and Rab6 but less significantly
      Rac1 proteins, indicating that these proteins were possible targets for ZOL
      induced actions. We further analyzed which small G proteins were responsible for
      the three ZOL-induced effects, caspase-mediated apoptosis, S-phase arrest and
      morphological changes, using inhibitors for respective small G proteins and siRNA
      for Cdc42. ZOL-induced apoptosis is due to insufficient prenylation of Rab
      proteins because an inhibitor of geranlygeranyl transferase II that was specific
      for Rab family proteins prenylation, but not others inhibitors, activated the
      same apoptotic pathways that ZOL did. ZOL suppressed an endogenous topoisomerase
      II activity, which was associated with apoptosis and S-phase arrest in respective
      cells because we detected the same cell cycle changes in etoposide-treated cells.
      Inhibitors for geranlygeranyl transferase I and for RhoA produced morphological
      changes and disrupted actin fiber structures, both of which were similar to those
      by ZOL treatments. These data demonstrated that anti-tumor effects by ZOL were
      attributable to inhibited functions of respective small G proteins and
      topoisomerase II activity, and suggested that cellular factors were involved in
      the differential cell cycle changes.

PMID- 25393474
TI  - CBAP promotes thymocyte negative selection by facilitating T-cell receptor
      proximal signaling.
AB  - T-cell receptor (TCR)-transduced signaling is critical to thymocyte development
      at the CD4/CD8 double-positive stage, but the molecules involved in this process
      are not yet fully characterized. We previously demonstrated that GM-CSF/IL-3/IL-5
      receptor common beta-chain-associated protein (CBAP) modulates ZAP70-mediated T
      cell migration and adhesion. On the basis of the high expression of CBAP during
      thymocyte development, we investigated the function of CBAP in thymocyte
      development using a CBAP knockout mouse. CBAP-deficient mice showed normal early
      thymocyte development and positive selection. In contrast, several negative
      selection models (including TCR transgene, superantigen staphylococcal
      enterotoxin B, and anti-CD3 antibody treatment) revealed an attenuation of TCR
      induced thymocyte deletion in CBAP knockout mice. This phenotype correlated with
      a reduced accumulation of BIM upon TCR crosslinking in CBAP-deficient thymocytes.
      Loss of CBAP led to reduced TCR-induced phosphorylation of proteins involved in
      both proximal and distal signaling events, including ZAP70, LAT, PLCgamma1, and
      JNK1/2. Moreover, TCR-induced association of LAT signalosome components was
      reduced in CBAP-deficient thymocytes. Our data demonstrate that CBAP is a novel
      component in the TCR signaling pathway and modulates thymocyte apoptosis during
      negative selection. 

PMID- 25393475
TI  - The Hippo pathway is controlled by Angiotensin II signaling and its reactivation
      induces apoptosis in podocytes.
AB  - The Hippo pathway fulfills a crucial function in controlling the balance between
      proliferation, differentiation and apoptosis in cells. Recent studies showed that
      G protein-coupled receptors (GPCRs) serve as upstream regulators of Hippo
      signaling, that either activate or inactivate the Hippo pathway via the large
      tumor suppressor kinase (LATS) and its substrate, the co-transcription factor Yes
      associated protein (YAP). In this study, we focused on the Angiotensin II type 1
      receptor (AT1R), which belongs to the GPCR family and has an essential role in
      the control of blood pressure and water homeostasis. We found that Angiotensin II
      (Ang II) inactivates the pathway by decreasing the activity of LATS kinase;
      therefore, leading to an enhanced nuclear shuttling of unphosphorylated YAP in
      HEK293T cells. This shuttling of YAP is actin-dependent as disruption of the
      actin cytoskeleton inhibited dephosphorylation of LATS and YAP. Interestingly, in
      contrast to HEK293T cells, podocytes, which are a crucial component of the
      glomerular filtration barrier, display a predominant nuclear YAP localization in
      vivo and in vitro. Moreover, stimulation with Ang II did not alter Hippo pathway
      activity in podocytes, which show a deactivated pathway. Reactivation of the LATS
      kinase activity in podocytes resulted in an increased cytoplasmic YAP
      localization accompanied by a strong induction of apoptosis. Thus, our work
      indicates that the control of LATS activation and subsequent YAP localization is
      important for podocyte homeostasis and survival. 

PMID- 25393477
TI  - Mitochondrial dysfunction-associated OPA1 cleavage contributes to muscle
      degeneration: preventative effect of hydroxytyrosol acetate.
AB  - Mitochondrial dysfunction contributes to the development of muscle disorders,
      including muscle wasting, muscle atrophy and degeneration. Despite the knowledge
      that oxidative stress closely interacts with mitochondrial dysfunction, the
      detailed mechanisms remain obscure. In this study, tert-butylhydroperoxide (t
      BHP) was used to induce oxidative stress on differentiated C2C12 myotubes. t-BHP
      induced significant mitochondrial dysfunction in a time-dependent manner,
      accompanied by decreased myosin heavy chain (MyHC) expression at both the mRNA
      and protein levels. Consistently, endogenous reactive oxygen species (ROS)
      overproduction triggered by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone
      (FCCP), a mitochondrial oxidative phosphorylation inhibitor, was accompanied by
      decreased membrane potential and decreased MyHC protein content. However, the
      free radical scavenger N-acetyl-L-cysteine (NAC) efficiently reduced the ROS
      level and restored MyHC content, suggesting a close association between ROS and
      MyHC expression. Meanwhile, we found that both t-BHP and FCCP promoted the
      cleavage of optic atrophy 1 (OPA1) from the long form into short form during the
      early stages. In addition, the ATPase family gene 3-like 2, a mitochondrial inner
      membrane protease, was also markedly increased. Moreover, OPA1 knockdown in
      myotubes was accompanied by decreased MyHC content, whereas NAC failed to prevent
      FCCP-induced MyHC decrease with OPA1 knockdown, suggesting that ROS might affect
      MyHC content by modulating OPA1 cleavage. In addition, hydroxytyrosol acetate (HT
      AC), an important compound in virgin olive oil, could significantly prevent t-BHP
      induced mitochondrial membrane potential and cell viability loss in myotubes.
      Specifically, HT-AC inhibited t-BHP-induced OPA1 cleavage and mitochondrial
      morphology changes, accompanied by improvement on mitochondrial oxygen
      consumption capacity, ATP productive potential and activities of mitochondrial
      complex I, II and V. Moreover, both t-BHP- and FCCP-induced MyHC decrease was
      sufficiently inhibited by HT-AC. Taken together, our data provide evidence
      indicating that mitochondrial dysfunction-associated OPA1 cleavage may contribute
      to muscle degeneration, and olive oil compounds could be effective nutrients for
      preventing the development of muscle disorders. 

PMID- 25393478
TI  - Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone
      formation by increasing chondrocyte survival.
AB  - Endochondral ossification is the result of chondrocyte differentiation,
      hypertrophy, death and replacement by bone. The careful timing and progression of
      this process is important for normal skeletal bone growth and development, as
      well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen
      activated protein kinase (MAPK), which is activated by reactive oxygen species
      and other cellular stress events. Activation of ASK1 initiates a signaling
      cascade known to regulate diverse cellular events including cytokine and growth
      factor signaling, cell cycle regulation, cellular differentiation, hypertrophy,
      survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes,
      but the role of ASK1 in skeletal tissues has not been investigated. Herein, we
      report that ASK1 knockout (KO) mice display alterations in normal growth plate
      morphology, which include a shorter proliferative zone and a lengthened
      hypertrophic zone. These changes in growth plate dynamics result in accelerated
      long bone mineralization and an increased formation of trabecular bone, which can
      be attributed to an increased resistance of terminally differentiated
      chondrocytes to undergo cell death. Interestingly, under normal cell culture
      conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no
      differences in either MAPK signaling or osteogenic or chondrogenic
      differentiation when compared with wild-type (WT) MEFs. However, when cultured
      with stress activators, H2O2 or staurosporine, the KO cells show enhanced
      survival, an associated decrease in the activation of proteins involved in death
      signaling pathways and a reduction in markers of terminal differentiation.
      Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO
      mice endochondral bone formation was increased in an ectopic ossification model.
      These findings highlight a previously unrealized role for ASK1 in regulating
      endochondral bone formation. Inhibition of ASK1 has clinical potential to treat
      fractures or to slow osteoarthritic progression by enhancing chondrocyte survival
      and slowing hypertrophy.

PMID- 25393481
TI  - Charge delocalization in an organic mixed valent bithiophene is greater than in a
      structurally analogous biselenophene.
AB  - A series of selenophenes with redox-active amine end-capping groups was
      synthesized and investigated. A combination of cyclic voltammetry, optical
      absorption, EPR spectroscopy, and quantum-chemical calculations based on Kohn
      Sham density functional theory was used to explore charge delocalization in the
      monocationic mixed-valence forms of these selenophenes, and the results were
      compared to those obtained from analogous studies of structurally identical
      thiophenes. The striking finding is that the comproportionation constant (Kc) for
      the experimentally investigated biselenophene is more than 2 orders of magnitude
      lower than for its bithiophene counterpart (in CH3CN with 0.1 M TBAPF6), and the
      electronic coupling between the two amine end-capping groups in the mixed-valent
      biselenophene monocation is only roughly half as strong as in the corresponding
      bithiophene monocation. These are surprisingly large differences given the
      structural similarity between the respective biselenophene and bithiophene
      molecules. However, the computationally determined comproportionation constants
      for biselenophene and bithiophene are almost identical, and the electronic
      coupling in the monocationic biselenophene is only slightly smaller than that in
      the monocationic bithiophene. We assume that the external electric field may be
      responsible for the differences in monocation stabilities between experiment and
      computation. Our findings indicate that charge delocalization across individual
      selenophenes tends to be less pronounced than across individual thiophenes, and
      this may have important implications for long-range charge transfer across
      selenophene oligomers or polymers. 

PMID- 25393479
TI  - Neuritin can normalize neural deficits of Alzheimer's disease.
AB  - Reductions in hippocampal neurite complexity and synaptic plasticity are believed
      to contribute to the progressive impairment in episodic memory and the mild
      cognitive decline that occur particularly in the early stages of Alzheimer's
      disease (AD). Despite the functional and therapeutic importance for patients with
      AD, intervention to rescue or normalize dendritic elaboration and synaptic
      plasticity is scarcely provided. Here we show that overexpression of neuritin, an
      activity-dependent protein, promoted neurite outgrowth and maturation of synapses
      in parallel with enhanced basal synaptic transmission in cultured hippocampal
      neurons. Importantly, exogenous application of recombinant neuritin fully
      restored dendritic complexity as well as spine density in hippocampal neurons
      prepared from Tg2576 mice, whereas it did not affect neurite branching of neurons
      from their wild-type littermates. We also showed that soluble recombinant
      neuritin, when chronically infused into the brains of Tg2576 mice, normalized
      synaptic plasticity in acute hippocampal slices, leading to intact long-term
      potentiation. By revealing the protective actions of soluble neuritin against AD
      related neural defects, we provide a potential therapeutic approach for patients
      with AD. 

PMID- 25393480
TI  - Docosahexaenoic acid induces the degradation of HPV E6/E7 oncoproteins by
      activating the ubiquitin-proteasome system.
AB  - The oncogenic human papillomavirus (HPV) E6/E7 proteins are essential for the
      onset and maintenance of HPV-associated malignancies. Here, we report that
      activation of the cellular ubiquitin-proteasome system (UPS) by the omega-3 fatty
      acid, docosahexaenoic acid (DHA), leads to proteasome-mediated degradation of
      E6/E7 viral proteins and the induction of apoptosis in HPV-infected cancer cells.
      The increases in UPS activity and degradation of E6/E7 oncoproteins were
      associated with DHA-induced overproduction of mitochondrial reactive oxygen
      species (ROS). Exogenous oxidative stress and pharmacological induction of
      mitochondrial ROS showed effects similar to those of DHA, and inhibition of ROS
      production abolished UPS activation, E6/E7 viral protein destabilization, and
      apoptosis. These findings identify a novel role for DHA in the regulation of UPS
      and viral proteins, and provide evidence for the use of DHA as a mechanistically
      unique anticancer agent for the chemoprevention and treatment of HPV-associated
      tumors. 

PMID- 25393482
TI  - Chemical analysis and risk assessment of prohibited colouring agents in face
      paint with special regard to CI 15585 (D&C Red No. 9, Pigment Red 53:1).
AB  - OBJECTIVES: Face painting in the colours of the national flags has become a mass
      phenomenon during international mega sporting events. Face paints, belonging to
      the group of lipophilic decorative cosmetics, pose an analytical challenge,
      especially in the sample preparation steps to obtain sample extracts of the
      colouring agents of low solubility. METHODS: In the context of official cosmetics
      control, a sample of German flag-coloured face paints (n = 42) offered during the
      soccer world cup 2014 was analysed. Sample-clean-up of hydroalcoholic and
      dichloromethane sample extracts was conducted using preparative thin-layer
      chromatography (TLC). For identification, analytical TLC, spectrophotometry
      considering bathochromic effects, and high-performance liquid chromatography (LC)
      with diode array detector were applied. Nuclear magnetic resonance (NMR)
      spectroscopy and LC-tandem mass spectrometry (LC-MS/MS) were used in positive
      cases for confirmatory analysis. NMR spectroscopy was also applied to determine
      the identity and purity of reference substances. Risk assessment was provided
      using the margin of exposure (MOE) methodology. RESULTS: The prohibited red
      colouring agent CI 15585 (D&C Red No. 9, Pigment Red 53:1), which is carcinogenic
      in animals, was positively identified in 40% of the analysed samples. Per face
      painting event, about 0.04 mg kg(-1) bw (adult) or 0.11 mg kg(-1) bw (child) of
      CI 15585 is systemically absorbed. Assuming an annual use of five times (adult)
      or 20 times (child), the exposure would be 5.8E-04 mg kg(-1) bw per day (adult)
      or 5.8E-03 mg kg(-1) bw per day (child). The MOE in these worst-case scenarios
      would be 6871 (adult) and 695 (child). Because the mechanism of CI 15585 is non
      genotoxic and the MOE is higher than a safety factor of 100, CI 15585 does not
      pose a serious health risk to the consumer, but should be avoided for reasons of
      precautionary public health protection. CONCLUSION: An analytical strategy to
      determine colouring agents in face paints was developed and non-compliance with
      the European Union (EU) cosmetic products regulation in a considerable number of
      products was detected. An increased control frequency especially at the points of
      entry into the EU is recommended.

PMID- 25393491
TI  - Protein dynamics: tuning disorder propensity in p53.

PMID- 25393492
TI  - Neuroinflammation: modulating mighty microglia.

PMID- 25393497
TI  - Investigation of Mn, Fe, and Ni incorporation in CeCo2Al8.
AB  - Single crystals of CeCo(2-x)M(x)Al(8) (M = Mn, Fe, Ni; 0 <= x < 1) were grown and
      characterized by X-ray diffraction and magnetic susceptibility. The unit cell
      volumes of Mn-doped compounds increase and those of Ni-doped compounds decrease
      with increasing dopant concentration. All samples display a magnetic ordering
      near 6 K with magnetic moments of the analogues ranging from 2.61 to 2.81
      MU(B)/mol Ce and slightly higher than Ce(3+) only magnetic moment. The unit cell
      volumes of Fe-doped compounds also increase with increasing Fe concentration.
      However, the cell volume of CeCo(2-x)Fe(x)Al(8) decreases for x = 1.00 and is not
      Curie-Weiss possibly because of valence fluctuation.

PMID- 25393493
TI  - Recent strategies targeting HIV glycans in vaccine design.
AB  - Although efforts to develop a vaccine against HIV have so far met with little
      success, recent studies of HIV-positive patients with strongly neutralizing sera
      have shown that the human immune system is capable of producing potent and
      broadly neutralizing antibodies (bnAbs), some of which neutralize up to 90% of
      HIV strains. These antibodies bind conserved vulnerable sites on the viral
      envelope glycoprotein gp120, and identification of these sites has provided
      exciting clues about the design of potentially effective vaccines. Carbohydrates
      have a key role in this field, as a large fraction of bnAbs bind carbohydrates or
      combinations of carbohydrate and peptide elements on gp120. Additionally,
      carbohydrates partially mask some peptide surfaces recognized by bnAbs. The use
      of engineered glycoproteins and other glycostructures as vaccines to elicit
      antibodies with broad neutralizing activity is therefore a key area of interest
      in HIV vaccine design. 

PMID- 25393498
TI  - Reconstruction of Head and Neck Capillary Malformations With Free Perforator
      Flaps for Aesthetic Purposes.
AB  - BACKGROUND: Capillary malformations (CMs) are composed of dilated capillaries and
      venules in the dermis layer. They appear as pink- or purple-colored lesions on
      the involved skin and usually follow a dermatomal distribution. Generally, laser
      treatment is considered the treatment of choice; however, in some patients, a
      surgical approach should be considered. This article presents the authors'
      experiences with free perforator flap transfer to the head and neck after
      resection of CMs for aesthetic purposes. PATIENTS AND METHODS: A total of 5
      patients with CMs on their head and neck underwent operations for aesthetic
      purposes. After lesion debulking, defect sizes were measured and precise flaps
      were designed. A primary flap-thinning procedure was needed in obese patients
      before flap inset. The donor site was closed primarily in 4 cases. RESULTS:
      Thoracodorsal artery perforator free flaps were performed in all patients. The
      average size of harvested flaps was 146.8 cm. All flaps survived without
      recurrence of CM on the skin paddle of the transferred flap. Aesthetic
      restoration and high patient satisfaction were achieved after the surgery.
      CONCLUSIONS: The authors used free flaps to improve aesthetic outcomes, which
      have been used for reconstruction after trauma and malignancy. Free perforator
      flap transfer should be considered a valuable option for head and neck CMs.

PMID- 25393501
TI  - A general catalytic route to isoindolinones and tetrahydroisoquinolines:
      application in the synthesis of (+/-)-crispine A.
AB  - An unprecedented highly efficient Lewis acid catalyzed one-pot cascade has been
      demonstrated as a general catalytic system for the synthesis of diversely
      substituted isoindolinones and tetrahydroisoquinolines. The cascade effects one C
      C and two C-N bond-forming events in one pot. Several interesting transformations
      of the products into valuable synthetic intermediates are featured with the
      successful total synthesis of (+/-)-crispine A. 

PMID- 25393500
TI  - Effects of histone acetylation status on the early development of in vitro
      porcine transgenic cloned embryos.
AB  - The purpose of this study was to investigate the effects of the histone
      deacetylase (HDAC) inhibitor trichostatin A (TSA) on transgene expression and
      development of porcine transgenic cloned embryos, specifically focusing on
      effects derived from TSA-treated donor cells or TSA-treated reconstructed
      embryos. The results showed that TSA treatment on reconstructed embryos modified
      the acetylation status, which significantly improved the development of porcine
      somatic cell nuclear transfer (SCNT) embryos in vitro, but not donor cells.
      Furthermore, the treatment of reconstructed embryos with TSA enhanced expression
      of the pluripotency-related gene POU5F1 and stimulated expression of the anti
      apoptotic gene BCL-2. Enhanced green fluorescent protein (EGFP) mRNA expression
      of every group dropped drastically from donor cells to blastocysts.
      Interestingly, TSA is likely to prevent a decline in EGFP expression in nuclear
      reprogramming of porcine SCNT embryos. However DNA hypomethylation induced by
      modified histone acetylation of donor cells treated with TSA was significantly
      more effective in increasing EGFP expression in SCNT blastocysts. In conclusion,
      the acetylation status of both donor cells and reconstructed embryos modified by
      TSA treatment increased transgene expression and improved nuclear reprogramming
      and the developmental potential of porcine transgenic SCNT embryos. 

PMID- 25393499
TI  - Hardware Removal in Craniomaxillofacial Trauma: A Systematic Review of the
      Literature and Management Algorithm.
AB  - BACKGROUND: Craniomaxillofacial (CMF) fractures are typically treated with open
      reduction and internal fixation. Open reduction and internal fixation can be
      complicated by hardware exposure or infection. The literature often does not
      differentiate between these 2 entities; so for this study, we have considered all
      hardware exposures as hardware infections. Approximately 5% of adults with CMF
      trauma are thought to develop hardware infections. Management consists of either
      removing the hardware versus leaving it in situ. The optimal approach has not
      been investigated. Thus, a systematic review of the literature was undertaken and
      a resultant evidence-based approach to the treatment and management of CMF
      hardware infections was devised. MATERIALS AND METHODS: A comprehensive search of
      journal articles was performed in parallel using MEDLINE, Web of Science, and
      ScienceDirect electronic databases. Keywords and phrases used were maxillofacial
      injuries; facial bones; wounds and injuries; fracture fixation, internal; wound
      infection; and infection. Our search yielded 529 articles. To focus on CMF
      fractures with hardware infections, the full text of English-language articles
      was reviewed to identify articles focusing on the evaluation and management of
      infected hardware in CMF trauma. Each article's reference list was manually
      reviewed and citation analysis performed to identify articles missed by the
      search strategy. There were 259 articles that met the full inclusion criteria and
      form the basis of this systematic review. The articles were rated based on the
      level of evidence. There were 81 grade II articles included in the meta-analysis.
      RESULT: Our meta-analysis revealed that 7503 patients were treated with hardware
      for CMF fractures in the 81 grade II articles. Hardware infection occurred in 510
      (6.8%) of these patients. Of those infections, hardware removal occurred in 264
      (51.8%) patients; hardware was left in place in 166 (32.6%) patients; and in 80
      (15.6%) cases, there was no report as to hardware management. Finally, our review
      revealed that there were no reported differences in outcomes between groups.
      CONCLUSIONS: Management of CMF hardware infections should be performed in a
      sequential and consistent manner to optimize outcome. An evidence-based algorithm
      for management of CMF hardware infections based on this critical review of the
      literature is presented and discussed.

PMID- 25393502
TI  - Broader expression of the mouse platelet factor 4-cre transgene beyond the
      megakaryocyte lineage.
AB  - BACKGROUND: Transgenic mice expressing cre recombinase under the control of the
      platelet factor 4 (Pf4) promoter, in the context of a 100-kb bacterial artificial
      chromosome, have become a valuable tool with which to study genetic modifications
      in the platelet lineage. However, the specificity of cre expression has recently
      been questioned, and the time of its onset during megakaryopoiesis remains
      unknown. OBJECTIVES/METHODS: To characterize the expression of this transgene, we
      used double-fluorescent cre reporter mice. RESULTS: In the bone marrow, Pf4-cre
      mediated recombination had occurred in all CD42-positive megakaryocytes as early
      as stage I of maturation, and in rare CD42-negative cells. In circulating blood,
      all platelets had recombined, along with only a minor fraction of CD45-positive
      cells. However, we found that all tissues contained recombined cells of
      monocyte/macrophage origin. When recombined, these cells might potentially modify
      the function of the tissues under particular conditions, especially inflammatory
      conditions, which further increase recombination in immune cells. Unexpectedly, a
      subset of epithelial cells from the distal colon showed signs of recombination
      resulting from endogenous Pf4-cre expression. This is probably the basis of the
      unexplained colon tumors developed by Apc(flox/flox) ;Pf4-cre mice, generated in
      a separate study on the role of Apc in platelet formation. CONCLUSION:
      Altogether, our results indicate early recombination with full penetrance in
      megakaryopoiesis, and confirm the value of Pf4-cre mice for the genetic
      engineering of megakaryocytes and platelets. However, care must be taken when
      investigating the role of platelets in processes outside hemostasis, especially
      when immune cells might be involved.

PMID- 25393503
TI  - Restless legs syndrome and post polio syndrome: a case-control study.
AB  - BACKGROUND AND PURPOSE: The aim was to investigate the prevalence of restless
      legs syndrome (RLS), fatigue and daytime sleepiness in a large cohort of patients
      affected by post polio syndrome (PPS) and their impact on patient health-related
      quality of life (HRQoL) compared with healthy subjects. METHODS: PPS patients
      were evaluated by means of the Stanford Sleepiness Scale and the Fatigue Severity
      Scale (FSS). The Short Form Health Survey (SF-36) questionnaire was utilized to
      assess HRQoL in PPS. RLS was diagnosed when standard criteria were met. Age and
      sex matched healthy controls were recruited amongst spouses or friends of PPS
      subjects. RESULTS: A total of 66 PPS patients and 80 healthy controls were
      enrolled in the study. A significantly higher prevalence of RLS (P < 0.0005; odds
      ratio 21.5; 95% confidence interval 8.17-57) was found in PPS patients (PPS/RLS+
      63.6%) than in healthy controls (7.5%). The FSS score was higher in PPS/RLS+ than
      in PPS/RLS- patients (P = 0.03). A significant decrease of SF-36 scores,
      including the physical function (P = 0.001), physical role (P = 0.0001) and
      bodily pain (P = 0.03) domains, was found in PPS/RLS+ versus PPS/RLS- patients.
      Finally, it was found that PPS/RLS+ showed a significant correlation between
      International Restless Legs Scale score and FSS (P < 0.0001), as well as between
      International Restless Legs Scale score and most of the SF-36 items (physical
      role P = 0.0018, general health P = 0.0009, vitality P = 0.0022, social
      functioning P = 0.002, role emotional P = 0.0019, and mental health P = 0.0003).
      CONCLUSION: Our findings demonstrate a high prevalence of RLS in PPS, and that
      RLS occurrence may significantly influence the HRQoL and fatigue of PPS patients.
      A hypothetical link between neuroanatomical and inflammatory mechanisms in RLS
      and PPS is suggested.

PMID- 25393504
TI  - Compared with what? An analysis of control-group types in Cochrane and Campbell
      reviews of psychosocial treatment efficacy with substance use disorders.
AB  - BACKGROUND AND AIMS: A crucial, but under-appreciated, aspect in experimental
      research on psychosocial treatments of substance use disorders concerns what
      kinds of control groups are used. This paper examines how the distinction between
      different control-group designs have been handled by the Cochrane and the
      Campbell Collaborations in their systematic reviews of psychosocial treatments of
      substance abuse disorders. METHODS: We assessed Cochrane and Campbell reviews (n
      = 8) that were devoted to psychosocial treatments of substance use disorders. We
      noted what control groups were considered and analysed the extent to which the
      reviews provided a rationale for chosen comparison conditions. We also analysed
      whether type of control group in the primary studies influenced how the reviews
      framed the effects discussed and whether this was related to conclusions drawn.
      RESULTS: The reviews covered studies involving widely different control
      conditions. Overall, little attention was paid to the use of different control
      groups (e.g. head-to-head comparisons versus untreated controls) and what this
      implies when interpreting effect sizes. Seven of eight reviews did not provide a
      rationale for the choice of comparison conditions. CONCLUSIONS: Cochrane and
      Campbell reviews of the efficacy of psychosocial interventions with substance use
      disorders seem to underappreciate that the use of different control-group types
      yields different effect estimates. Most reviews have not distinguished between
      different control-group designs and therefore have provided a confused picture
      regarding absolute and relative treatment efficacy. A systematic approach to
      treating different control-group designs in research reviews is necessary for
      meaningful estimates of treatment efficacy.

PMID- 25393506
TI  - Clinical application of asparaginase activity levels following treatment with
      pegaspargase.
AB  - Asparaginase, an enzyme used to treat acute lymphoblastic leukemia and related
      forms of nonHodgkin lymphoma, depletes asparagine, which leads to lymphoblast
      cell death. Unlike most chemotherapeutic agents, asparaginase is a foreign
      protein that can result in clinical allergy and/or silent hypersensitivity with
      production of neutralizing antibodies that inactivate asparaginase. In North
      America, asparaginase activity levels can now be obtained via a commercially
      available assay, for therapeutic drug monitoring and investigation of potential
      allergic reactions. Herein, we provide recommendations and a corresponding
      algorithm for the clinical application of this assay after treatment with
      pegaspargase to evaluate suspected hypersensitivity reactions and/or silent
      inactivation.

PMID- 25393505
TI  - Advances in exploring the role of microRNAs in the pathogenesis, diagnosis and
      therapy of cardiac diseases in China.
AB  - Cardiovascular disease has become the most serious health threat and represents
      the major cause of morbidity and mortality in China, as in other industrialized
      nations. During the past few decades, China's economic boom has tremendously
      improved people's standard of living but has also changed their lifestyle,
      increasing the prevalence of cardiovascular disease, the so-called 'disease of
      modern civilization'. This new trend has attracted a significant amount of
      research. Many of the studies conducted by Chinese investigators are orientated
      towards understanding the molecular mechanisms of cardiovascular disease. At the
      molecular level, the long-standing consensus is that cardiovascular disease is
      associated with a sequence mutation (genetic anomaly) and expression deregulation
      (epigenetic disorder) of protein-coding genes. However, new research data have
      established the non-protein-coding genes microRNAs (miRNAs) as a central
      regulator of the pathogenesis of cardiac disease and a potential new therapeutic
      target for cardiovascular disease. These small non-coding RNAs have also been
      subjected to extensive, rigorous investigations by Chinese researchers. Over the
      years, a large body of studies on miRNAs in cardiovascular disease has been
      conducted by Chinese investigators, yielding fruitful research results and a
      better understanding of miRNAs as a new level of molecular mechanisms for the
      pathogenesis of cardiac disease. In this review, we briefly summarize the current
      status of research in the field of miRNAs and cardiovascular disease in China,
      highlighting the advances made in elucidating the role of miRNAs in various
      cardiac conditions, including cardiac arrhythmia, myocardial ischaemia, cardiac
      hypertrophy and heart failure. We have also examined the potential of miRNAs as
      novel diagnostic biomarkers and therapeutic targets.

PMID- 25393507
TI  - The structural basis for enhanced silver reflectance in Koi fish scale and skin.
AB  - Fish have evolved biogenic multilayer reflectors composed of stacks of
      intracellular anhydrous guanine crystals separated by cytoplasm, to produce the
      silvery luster of their skin and scales. Here we compare two different variants
      of the Japanese Koi fish; one of them with enhanced reflectivity. Our aim is to
      determine how biology modulates reflectivity, and from this to obtain a
      mechanistic understanding of the structure and properties governing the intensity
      of silver reflectance. We measured the reflectance of individual scales with a
      custom-made microscope, and then for each individual scale we characterized the
      structure of the guanine crystal/cytoplasm layers using high-resolution cryo-SEM.
      The measured reflectance and the structural-geometrical parameters were used to
      calculate the reflectance of each scale, and the results were compared to the
      experimental measurements. We show that enhanced reflectivity is obtained with
      the same basic guanine crystal/cytoplasm stacks, but the structural arrangement
      between the stack, inside the stacks, and relative to the scale surface is varied
      when reflectivity is enhanced. Finally, we propose a model that incorporates the
      basic building block parameters, the crystal orientation inside the tissue, and
      the resulting reflectance and explains the mechanistic basis for reflectance
      enhancement. 

PMID- 25393508
TI  - Potential roles of BMP9 in liver fibrosis.
AB  - Liver fibrosis is a common phenomenon that is associated with several pathologies
      and is characterized by excessive extracellular matrix deposition that leads to
      progressive liver dysfunction. Bone morphogenetic protein 9 (BMP9) is the most
      recently discovered member of the BMP family. BMP9 bound with high affinity to
      activin receptor-like kinase 1 (ALK1) and endoglin in non-parenchymal liver
      cells. In addition, BMP9 activated Smad1/Smad5/Smad8 and induced the expression
      of the target genes inhibitor of differentiation 1 (Id1), hepcidin, Snail and the
      co-receptor endoglin in liver cells. Although the role of BMP9 in liver fibrosis
      is currently poorly understood, the presence of BMP9-activated proteins and its
      target genes have been reported to be associated with liver fibrosis development.
      This review summarizes the indirect connection between BMP9 and liver fibrosis,
      with a focus on the BMP9 signaling pathway members ALK1, endoglin, Id1, hepcidin
      and Snail. The observations on the role of BMP9 in regulating liver fibrosis may
      help in understanding the pathology mechanisms of liver disease. Furthermore,
      BMP9 could be served as a potent biomarker and the target of potential
      therapeutic drugs to treat hepatocytes fibrosis. 

PMID- 25393509
TI  - Characterization of flavonoid glycosides from fenugreek (Trigonella foenum
      graecum) crude seeds by HPLC-DAD-ESI/MS analysis.
AB  - Fenugreek (Trigonella foenum-graecum) is a medicinal plant which is widely used
      for its pharmacological properties. In this study the phenolic composition of
      fenugreek crude seeds originating from Morocco has been investigated. Extraction
      was performed from defatted seeds by a hydromethanolic solution using an
      Accelerated Solvent Extractor. HPLC technique coupled to negative ion
      electrospray ionization mass spectrometry and diode array detection was employed
      to identify the polyphenol in the obtained extract. The obtained results allowed
      the detection of 32 phenolic compounds among which various flavonoid glycosides
      and phenolic acids have been tentatively identified on the basis of their UV and
      MS spectra, and comparisons with standards when available, as well as with
      literature data. A systematic study of the obtained MS spectra and the observed
      fragmentation showed that most of the identified compounds were acylated and non
      acylated flavonoids with apigenin, luteolin and kaempferol as aglycons.
      Hydroxycinnamic acids mostly dominated by caffeic acid derivatives were also
      detected. The quantitative analysis of the identified compounds showed that the
      phenolic composition of the studied crude fenugreek seeds was predominantly
      acylated and non-acylated flavone derivatives with apigenin as the main aglycon. 

PMID- 25393510
TI  - Berteroin present in cruciferous vegetables exerts potent anti-inflammatory
      properties in murine macrophages and mouse skin.
AB  - Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in
      cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and
      mustard oil. We examined whether berteroin exerts anti-inflammatory activities
      using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models.
      Berteroin decreased LPS-induced release of inflammatory mediators and pro
      inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced
      degradation of inhibitor of kappaBalpha (IkappaBalpha) and nuclear factor-kappaB
      p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin
      suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of
      transforming growth factor beta activated kinase-1. Berteroin also inhibited LPS
      induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin
      effectively suppressed TPA-induced edema formation and down-regulated iNOS and
      COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results
      demonstrate that berteroin exhibits potent anti-inflammatory properties and
      suggest that berteroin can be developed as a skin anti-inflammatory agent. 

PMID- 25393511
TI  - Microbial growth parameters obtained from the analysis of time to detection data
      using a novel rearrangement of the Baranyi-Roberts model.
AB  - AIMS: To explore the predictions of a novel rearrangement of the Baranyi-Roberts
      model (BRM) with time to detection data obtained from optical density data of
      microbial growth. METHODS AND RESULTS: Growth of Escherichia coli and Salmonella
      Typhimurium under mild conditions of temperature (25-37 degrees C), salt (0.086,
      0.51 and 1.03 mol l(-1)) and pH (6.85-4.5) was examined using optical density.
      Time to detection (TTD) data were fitted to a model based on a rearrangement of
      the BRM. Observations showed compatibility with standard viable count studies and
      produced highly accurate specific growth rates and lag phase durations. At high
      salt and low pH, however, there was a substantial dependency on the initial
      inoculum for the observation of visible growth. At 30 and 37 degrees C, with 1.03
      mol l(-1) salt, and at pH <5.75, no visible growth was recorded for E. coli at
      initial inoculum levels below 10(7) CFU ml(-1). CONCLUSIONS: The rearranged BRM
      can be used directly with TTD data obtained from optical density measurements.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A distinct advantage of the rearranged
      model is that it allows for a very simple interpretation of easily obtainable
      data using standard nonlinear regression. The rearranged model gives to TTD data
      the same modelling capability that the BRM gives to plate count data.

PMID- 25393512
TI  - Structure-function mapping of key determinants for hydrocarbon biosynthesis by
      squalene and squalene synthase-like enzymes from the green alga Botryococcus
      braunii race B.
AB  - Squalene and botryococcene are branched-chain, triterpene compounds that arise
      from the head-to-head condensation of two molecules of farnesyl diphosphate to
      yield 1'-1 and 1'-3 linkages, respectively. The enzymes that catalyze their
      formation have attracted considerable interest from the medical field as
      potential drug targets and the renewable energy sector for metabolic engineering
      efforts. Recently, the enzymes responsible for botryococcene and squalene
      biosynthesis in the green alga Botryococcus braunii race B were characterized. To
      better understand how the specificity for the 1'-1 and 1'-3 linkages was
      controlled, we attempted to identify the functional residues and/or domains
      responsible for this step in the catalytic cascade. Existing crystal structures
      for the mammalian squalene synthase and Staphylococcus dehydrosqualene synthase
      enzymes were exploited to develop molecular models for the B. braunii
      botryococcene and squalene synthase enzymes. Residues within the active sites
      that could mediate catalytic specificity were identified, and reciprocal mutants
      were created in an attempt to interconvert the reaction product specificity of
      the enzymes. We report here the identification of several amino acid positions
      contributing to the rearrangement of the cyclopropyl intermediate to squalene,
      but these same positions do not appear to be sufficient to account for the
      cyclopropyl rearrangement to give botryococcene. 

PMID- 25393514
TI  - Accounting for Sitting and Moving: An Analysis of Sedentary Behavior in Mass
      Media Campaigns.
AB  - BACKGROUND: Mass media campaigns are an important tool for promoting health
      related physical activity. The relevance of sedentary behavior to public health
      has propelled it to feature prominently in health campaigns across the world.
      This study explored the use of messages regarding sedentary behavior in health
      campaigns within the context of current debates surrounding the association
      between sedentary behavior and health, and messaging strategies to promote
      moderate-to-vigorous physical activity (MVPA). METHODS: A web-based search of
      major campaigns in the United Kingdom, United States, Canada, and Australia was
      performed to identify the main campaign from each country. A directed content
      analysis was then conducted to analyze the inclusion of messages regarding
      sedentary behavior in health campaigns and to elucidate key themes. Important
      areas for future research were illustrated. RESULTS: Four key themes from the
      campaigns emerged: clinging to sedentary behavior guidelines, advocating reducing
      sedentary behavior as a first step on the activity continuum and the importance
      of light activity, confusing the promotion of MVPA, and the demonization of
      sedentary behavior. CONCLUSIONS: Strategies for managing sedentary behavior as an
      additional complicating factor in health promotion are urgently required. Lessons
      learned from previous health communication campaigns should stimulate research to
      inform future messaging strategies.

PMID- 25393513
TI  - Incremental large and small muscle mass exercise in patients with heart failure:
      evidence of preserved peripheral haemodynamics and metabolism.
AB  - AIM: Doubt still remains as to whether peripheral vascular and skeletal muscle
      dysfunction accompanies the compromised cardiac function associated with heart
      failure with reduced ejection fraction (HFrEF). The aim of this study was to
      examine the effect of HFrEF on the haemodynamic and metabolic responses to
      exercise with both a large (cycle) and a small [knee extensor (KE)] muscle mass
      in comparison with well-matched healthy controls (Ctrls). METHODS: Utilizing
      blood sampling and thermodilution blood flow measurements, we studied incremental
      cycle and KE exercise in 12 patients with HFrEF (ejection fraction: 25 +/- 3%)
      and eight Ctrls. RESULTS: Incremental cycle exercise in both groups [heart
      failure with reduced ejection fraction (HFrEF): 23 +/- 1 to 116 +/- 10; Ctrls: 22
      +/- 1 to 137 +/- 5 W] resulted in a similar rise in blood flow (HFrEF: 1525 +/-
      132 to 4216 +/- 408; Ctrls: 1774 +/- 161 to 4713 +/- 448 mL min(-1)), oxygen
      uptake (HFrEF: 206 +/- 24 to 586 +/- 34; Ctrls: 252 +/- 21 to 747 +/- 89 mL min(
      1)) and lactate efflux across the leg (HFrEF: 479 +/- 122 to 4929 +/- 1255;
      Ctrls: 537 +/- 155 to 5776 +/- 1010 mm min(-1)). Vascular resistance fell
      similarly in both groups with increasing exercise intensity (HFrEF: 66 +/- 10 to
      24 +/- 3; Ctrls: 69 +/- 12 to 24 +/- 4 mmHg L(-1) min(-1) ). Incremental KE
      exercise also revealed similar haemodynamic and metabolic responses in both Ctrls
      and patients. CONCLUSION: Although assessed in a relatively small cohort, these
      data reveal that, when compared with well-matched healthy Ctrls, alterations in
      peripheral haemodynamics and skeletal muscle metabolism during exercise may not
      be an obligatory accompaniment to HFrEF.

PMID- 25393515
TI  - Minimizing morbidity in microvascular surgery: small-caliber anastomotic vessels
      and minimal access approaches.
AB  - IMPORTANCE: Minimizing morbidity when performing free flap reconstruction of the
      head and neck is important in the overall reconstructive paradigm. OBJECTIVE: To
      examine the indications and success rates of free tissue transfer using small
      caliber facial recipient vessels and minimal access incisions. DESIGN, SETTING,
      AND PARTICIPANTS: Retrospective medical record review of patients with head and
      neck defects undergoing free tissue transfer from May 2010 to June 2013 at 2
      tertiary care academic medical centers. INTERVENTIONS: Free tissue transfer using
      small-caliber recipient vessels and minimal access approaches. MAIN OUTCOMES AND
      MEASURES: Postoperative complications, including flap failure, requirement for
      revision surgery, and nerve dysfunction. RESULTS: Eighty-nine flaps in 86
      patients met inclusion criteria. Fifty flaps used the facial artery and vein
      distal to the facial notch, and 33 flaps used the superficial temporal vascular
      system. Six flaps used the angular artery and vein. A variety of flap donor sites
      were included. In most cases, free tissue transfer was indicated for the
      reconstruction of defects secondary to extirpation of malignant neoplasia.
      Overall success rate was 97.7% with 2 instances of total flap loss and 1 partial
      loss. One patient had transient nerve weakness (frontal branch), which resolved
      during a follow-up of 9 months. CONCLUSIONS AND RELEVANCE: Free tissue
      reconstruction of head and neck defects can be safely and reliably accomplished
      using small-caliber recipient vessels, such as the superficial temporal, distal
      facial, and angular vessels. Minimal access approaches for microvascular
      anastomosis may be performed with excellent cosmesis and minimal morbidity. LEVEL
      OF EVIDENCE: 4.

PMID- 25393518
TI  - Potential respiratory pathogens colonisation of the denture plaque of patients
      with chronic obstructive pulmonary disease.
AB  - INTRODUCTION: The role of bacterial infections in acute exacerbations of chronic
      obstructive pulmonary disease (COPD) is widely examined. Denture plaque in
      patients with COPD is an example of bacterial and fungal biofilm, which is a
      reservoir of potentially pathogenic respiratory tract microorganisms. Poor
      denture hygiene might cause acute exacerbations of COPD. OBJECTIVE: Assessment of
      prevalence of respiratory tract pathogens in denture plaque in stable patients
      with COPD and it influence on oral ontocenoses depending upon the therapy.
      MATERIALS AND METHODS: The study was based on the clinical assessment of oral
      mucosa and denture hygiene in 53 patients with COPD with mean age of 70 +/- 18
      years and 14 generally healthy participants with mean age of 65 +/- 14 years.
      Microbiological and mycological tests were performed by culturing direct denture
      swabs. RESULTS: The study showcased the presence of potential pathogenic micro
      organisms in denture plaque of 48 patients with COPD (90%) and nine healthy
      subjects (64.3%). Yeast-like fungi prevailed in denture surface swabs of 40 (75%)
      in patients with COPD and 8 (57%) in cases of control group. In 66% of patients,
      various degree of oral mucosa inflammation prevailed. CONCLUSIONS: Denture plaque
      could be a potential source of bacterial and fungal infections in patients with
      COPD.

PMID- 25393516
TI  - 2'-Deoxymugineic acid promotes growth of rice (Oryza sativa L.) by orchestrating
      iron and nitrate uptake processes under high pH conditions.
AB  - Poaceae plants release 2'-deoxymugineic acid (DMA) and related phytosiderophores
      to chelate iron (Fe), which often exists as insoluble Fe(III) in the rhizosphere,
      especially under high pH conditions. Although the molecular mechanisms behind the
      biosynthesis and secretion of DMA have been studied extensively, little
      information is known about whether DMA has biological roles other than chelating
      Fe in vivo. Here, we demonstrate that hydroponic cultures of rice (Oryza sativa)
      seedlings show almost complete restoration in shoot height and soil-plant
      analysis development (SPAD) values after treatment with 3-30 MUm DMA at high pH
      (pH 8.0), compared with untreated control seedlings at normal pH (pH 5.8). These
      changes were accompanied by selective accumulation of Fe over other metals. While
      this enhanced growth was evident under high pH conditions, DMA application also
      enhanced seedling growth under normal pH conditions in which Fe was fairly
      accessible. Microarray and qRT-PCR analyses revealed that exogenous DMA
      application attenuated the increased expression levels of various genes related
      to Fe transport and accumulation. Surprisingly, despite the preferential
      utilization of ammonium over nitrate as a nitrogen source by rice, DMA
      application also increased nitrate reductase activity and the expression of genes
      encoding high-affinity nitrate transporters and nitrate reductases, all of which
      were otherwise considerably lower under high pH conditions. These data suggest
      that exogenous DMA not only plays an important role in facilitating the uptake of
      environmental Fe, but also orchestrates Fe and nitrate assimilation for optimal
      growth under high pH conditions.

PMID- 25393517
TI  - Antigen-induced regulation of T-cell motility, interaction with antigen
      presenting cells and activation through endogenous thrombospondin-1 and its
      receptors.
AB  - Antigen recognition reduces T-cell motility, and induces prolonged contact with
      antigen-presenting cells and activation through mechanisms that remain unclear.
      Here we show that the T-cell receptor (TCR) and CD28 regulate T-cell motility,
      contact with antigen-presenting cells and activation through endogenous
      thrombospondin-1 (TSP-1) and its receptors low-density lipoprotein receptor
      related protein 1 (LRP1), calreticulin and CD47. Antigen stimulation induced a
      prominent up-regulation of TSP-1 expression, and transiently increased and
      subsequently decreased LRP1 expression whereas calreticulin was unaffected. This
      antigen-induced TSP-1/LRP1 response down-regulated a motogenic mechanism directed
      by LRP1-mediated processing of TSP-1 in cis within the same plasma membrane while
      promoting contact with antigen-presenting cells and activation through cis
      interaction of the C-terminal domain of TSP-1 with CD47 in response to N-terminal
      TSP-1 triggering by calreticulin. The antigen-induced TSP-1/LRP1 response
      maintained a reduced but significant motility level in activated cells. Blocking
      CD28 co-stimulation abrogated LRP1 and TSP-1 expression and motility. TCR/CD3
      ligation alone enhanced TSP-1 expression whereas CD28 ligation alone enhanced
      LRP1 expression. Silencing of TSP-1 inhibited T-cell conjugation to antigen
      presenting cells and T helper type 1 (Th1) and Th2 cytokine responses. The Th1
      response enhanced motility and increased TSP-1 expression through interleukin-2,
      whereas the Th2 response weakened motility and reduced LRP1 expression through
      interleukin-4. Ligation of the TCR and CD28 therefore elicits a TSP-1/LRP1
      response that stimulates prolonged contact with antigen-presenting cells and,
      although down-regulating motility, maintains a significant motility level to
      allow serial contacts and activation. Th1 and Th2 cytokine responses
      differentially regulate T-cell expression of TSP-1 and LRP1 and motility. 

PMID- 25393519
TI  - Implementing stationary-phase optimized selectivity in supercritical fluid
      chromatography.
AB  - The performance of stationary-phase optimized selectivity liquid chromatography
      (SOS-LC) for improved separation of complex mixtures has been demonstrated
      before. A dedicated kit containing column segments of different lengths and
      packed with different stationary phases is commercially available together with
      algorithms capable of predicting and ranking isocratic and gradient separations
      over vast amounts of possible column combinations. Implementation in
      chromatographic separations involving compressible fluids, as is the case in
      supercritical fluid chromatography, had thus far not been attempted. The
      challenge of this approach is the dependency of solute retention with the mobile
      phase density, complicating linear extrapolation of retention over longer or
      shorter columns segments, as is the case in conventional SOS-LC. In this study,
      the possibilities of performing stationary-phase optimized selectivity
      supercritical fluid chromatography (SOS-SFC) are demonstrated with typical low
      density mobile phases (94% CO2). The procedure is optimized with the commercially
      available column kit and with the classical isocratic SOS-LC algorithm. SOS-SFC
      appears possible without any density correction, although optimal correspondence
      between prediction and experiment is obtained when isopycnic conditions are
      maintained. As also the influence of the segment order appears significantly less
      relevant than expected, the use of the approach in SFC appears as promising as is
      the case in HPLC. Next to the classical use of SOS for faster baseline separation
      of all solutes in a mixture, the benefits of the approach for predicting as wide
      as possible separation windows around to-be-purified solutes in semipreparative
      SFC are illustrated, leading to significant production rate improvements in
      (semi)preparative SFC. 

PMID- 25393520
TI  - Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium
      complex lung disease.
AB  - RATIONALE: Although intermittent, three-times-weekly therapy is recommended for
      the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium
      complex (MAC) lung disease, supporting data are limited. OBJECTIVES: To evaluate
      the clinical efficacy of intermittent therapy compared with daily therapy for
      nodular bronchiectatic MAC lung disease. METHODS: A retrospective cohort study of
      217 patients with treatment-naive noncavitary nodular bronchiectatic MAC lung
      disease. All patients received either daily (n = 99) or intermittent therapy (n =
      118) that included clarithromycin or azithromycin, rifampin, and ethambutol.
      MEASUREMENTS AND MAIN RESULTS: Modification of the initial antibiotic therapy
      occurred more frequently in the daily therapy group than in the intermittent
      therapy group (46 vs. 21%; P < 0.001); in particular, ethambutol was more
      frequently discontinued in the daily therapy group than in the intermittent
      therapy group (24 vs. 1%; P <= 0.001). However, the rates of symptomatic
      improvement, radiographic improvement, and sputum culture conversion were not
      different between the two groups (daily therapy vs. intermittent therapy: 75 vs.
      82%, P = 0.181; 68 vs. 73%, P = 0.402; 76 vs. 67%, P = 0.154, respectively). In
      addition, the adjusted proportion of sputum culture conversion was similar
      between the daily therapy (71.3%; 95% confidence interval, 59.1-81.1%) and the
      intermittent therapy groups (73.6%; 95% confidence interval, 62.9-82.2%; P =
      0.785). CONCLUSIONS: These results suggest that intermittent three-times-weekly
      therapy with a macrolide, rifampin, and ethambutol is a reasonable initial
      treatment regimen for patients with noncavitary nodular bronchiectatic MAC lung
      disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00970801).

PMID- 25393521
TI  - Weak prediction power of the Framingham Risk Score for coronary artery disease in
      nonagenarians.
AB  - BACKGROUND: Coronary artery disease (CAD) is caused by an acute myocardial
      infarction and is still feared as a life-threatening heart disease worldwide. In
      order to identify patients at high risk for CAD, previous studies have proposed
      various risk assessment scores for the prevention of CAD. The most commonly used
      risk assessment score for CAD worldwide is the Framingham Risk Score (FRS). The
      FRS is used for middle-aged people; hence, its appropriateness has not been
      demonstrated to predict the likelihood of CAD occurrence in very elderly people.
      This article examines the possible predictive value of FRS for CAD in very
      elderly people over 90 years of age. METHODS: Data on all patients over 90 years
      of age who received a cardiac catheter were collected from hospital charts from
      the Department of Internal Medicine, Saarland University Medical Center, and
      HELIOS Hospital Wuppertal, Witten/Herdecke University Medical Center, Germany,
      within a study period from 2004 to 2013. The FRSs and cardiovascular risk
      profiles of patients over 90 years of age with and without CAD after cardiac
      catheterization were compared. RESULTS: One hundred and seventy-five (91.15%,
      mean age 91.51+/-1.80 years, 74 females [42.29%]; 95% confidence interval [CI],
      0.87-0.95) of a total 192 of the very elderly patients were found to have CAD.
      Based on the results of our study, the FRS seems to provide weak predictive
      ability for CAD in very elderly people (P = 0.3792). CONCLUSION: We found weak
      prediction power of FRS for CAD in nonagenarians.

PMID- 25393522
TI  - Analysis of trace microcystins in vegetables using solid-phase extraction
      followed by high performance liquid chromatography triple-quadrupole mass
      spectrometry.
AB  - A selective and sensitive method for the simultaneous detection of three common
      and hazardous microcystins (microcystins-LR, -RR, and -YR) in various vegetables
      was established using solid-phase extraction followed by high performance liquid
      chromatography coupled with mass spectrometry. The methanol-water proportion
      ratio of the extraction solvent and its acidity, as well as the efficiencies of
      solid-phase extraction, were evaluated to optimize a pretreatment procedure for
      extracting the microcystins from 10 vegetable matrices. The limits of detection
      and quantitation were below 7.5 MUg/kg (dw) and 25 MUg/kg (dw), respectively, in
      different vegetable matrices. The recoveries of the microcystins in the 10
      vegetable matrices ranged from 61.3 to 117.3%, with RSDs of 0.2-18.3%. The
      established method was used to analyze 28 field vegetable samples collected from
      the sides of Lake Dianchi, and microcystin-RR was found in almost all samples at
      concentrations of 36.4-2352.2 MUg/kg (dw). 

PMID- 25393523
TI  - Membrane protein oxidation determines neuronal degeneration.
AB  - Oxidative stress is an early hallmark in neurodegenerative disorders such as
      Alzheimer's and Parkinson's diseases. However, the critical biochemical effector
      mechanisms of oxidative neurotoxicity have remained surprisingly elusive. In
      screening various peroxides and potential substrates of oxidation for their
      effect on neuronal survival, we observed that intramembrane compounds were
      significantly more active than aqueous or amphiphilic compounds. To better
      understand this result, we synthesized a series of competitive and site-specific
      membrane protein oxidation inhibitors termed aminoacyllipids, whose structures
      were designed on the basis of amino acids frequently found at the protein-lipid
      interface of synaptic membrane proteins. Investigating the aminoacyllipids in
      primary neuronal culture, we found that the targeted protection of transmembrane
      tyrosine and tryptophan residues was sufficient to prevent neurotoxicity evoked
      by hydroperoxides, kainic acid, glutathione-depleting drugs, and certain
      amyloidogenic peptides, but ineffective against non-oxidative inducers of
      apoptosis such as sphingosine or Akt kinase inhibitors. Thus, the oxidative
      component of different neurotoxins appears to converge on neuronal membrane
      proteins, irrespective of the primary mechanism of cellular oxidant generation.
      Our results indicate the existence of a one-electron redox cycle based on
      membrane protein aromatic surface amino acids, whose disturbance or overload
      leads to excessive membrane protein oxidation and neuronal death. Membrane
      proteins have rarely been investigated as potential victims of oxidative stress
      in the context of neurodegeneration. This study provides evidence that excessive
      one-electron oxidation of membrane proteins from within the lipid bilayer,
      depicted in the graphic, is a functionally decisive step toward neuronal cell
      death in response to different toxins. 

PMID- 25393525
TI  - An extremely bulky tris(pyrazolyl)methanide: a tridentate ligand for the
      synthesis of heteroleptic magnesium(II) and ytterbium(II) alkyl, hydride, and
      iodide complexes.
AB  - The tris(pyrazolyl)methane compound HC(3-Ad-5-Mepz)3 [1, 3-Ad-5-Mepz=3-(1
      adamantyl)-5-methylpyrazolyl] and its regioisomer, HC(3-Ad-5-Mepz)2 (3-Me-5
      Adpz), were synthesized and crystallographically characterized. Deprotonation of
      1 with MeLi afforded the lithium complex [{kappa(3) -N-C(3-Ad-5-Mepz)3 }Li(thf)],
      which incorporates a tris(pyrazolyl)methanide ligand of unprecedented bulk.
      Reaction of 1 with MeMgI gave the ionic coordination complex [{kappa(3) -N-HC(3
      Ad-5-Mepz)3 }MgMe]I, which was readily deprotonated to afford the neutral
      compound [{kappa(3) -N-C(3-Ad-5-Mepz)3 }MgMe]. The related magnesium butyl
      compound [{kappa(3) -N-C(3-Ad-5-Mepz)3 }MgBu] was prepared from the reaction of 1
      and MgBu2 . Treating this with LiAlH4 or LiAlD4 led to rare examples of terminal
      magnesium hydride/deuteride complexes, [{kappa(3) -N-C(3-Ad-5-Mepz)3 }MgH/D]. All
      neutral magnesium alkyl and hydride compounds were crystallographically
      authenticated. Reaction of [{kappa(3) kappaN-C(3-Ad-5-Mepz)3 }Li(thf)] with [YbI2
      (thf)2 ] yielded the first structurally characterized f-block
      tris(pyrazolyl)methanide complex, [{kappa(3) -N-C(3-Ad-5-Mepz)3 }YbI(thf)]. 

PMID- 25393524
TI  - Fetal growth and preterm birth in children exposed to maternal or paternal
      rheumatoid arthritis: a nationwide cohort study.
AB  - OBJECTIVE: To assess indicators of fetal growth and risk of preterm birth in
      children of parents with rheumatoid arthritis (RA). METHODS: Through linkage of
      Danish national registries, we identified all children born in Denmark between
      1977 and 2008. We used general linear regression models to estimate mean
      differences in indicators of fetal growth among children with a parent with RA
      compared to unexposed children. Odds ratios (ORs) and 95% confidence intervals
      (95% CIs) of preterm birth were calculated using a logistic regression model.
      RESULTS: Of the 1,917,723 children included, a total of 13,556 children were
      exposed to maternal RA or maternal preclinical RA. Children exposed to maternal
      RA (n = 2,101) had approximately similar length, head circumference, and
      abdominal circumference at birth compared with children of mothers without RA.
      Birth weight was 87 gm lower (mean difference -87.04 gm [95% CI -111.23, -62.84])
      and placenta weight was 14 gm lower (-13.45 gm [95% CI -21.46, -5.43]) than those
      in children of mothers without RA. Rather similar results were found in children
      exposed to maternal preclinical RA (n = 11,455). Compared with unexposed
      children, a higher risk of preterm birth was found in children exposed to
      maternal RA (OR 1.48 [95% CI 1.20, 1.84]) and preclinical RA (OR 1.32 [95% CI
      1.07, 1.64]). No associations were found with paternal RA. CONCLUSION: Children
      exposed to either maternal RA or maternal preclinical RA are more often born
      preterm. However, indicators of fetal growth measured at birth were only slightly
      lower than those in unexposed children.

PMID- 25393526
TI  - Mesenchymal stem cells and ligand incorporation in biomimetic poly(ethylene
      glycol) hydrogels significantly improve insulin secretion from pancreatic islets.
AB  - The main goal of this study was to investigate pancreatic islet function with
      mesenchymal stem cells (MSCs) in a ligand-functionalized poly(ethylene glycol)
      (PEG) hydrogel for the treatment of type 1 diabetes (T1D). Rat bone marrow
      derived MSCs (rBM-MSCs) were encapsulated within synthetic PEG hydrogel, and cell
      viability and apoptosis within this 3D environment was examined in detail. ATP
      content and caspase-3 activity of encapsulated MSCs showed that fibronectin
      derived RGDS, laminin-derived IKVAV and/or insulinotropic glucagon-like peptide
      (GLP-1) were required to maintain MSC survival. Incorporation of these peptides
      into the hydrogel environment also improved pancreatic islet viability, where
      combinations of peptides had altered effects on islet survival. GLP-1 alone was
      the leading stimulator for insulin secretion. Cell adhesion peptides RGDS and
      IKVAV improved insulin secretion only when they were used in combination, but
      could not surpass the effect of GLP-1. Further, when pancreatic islets were co
      encapsulated with MSCs within synthetic PEG hydrogel, a two-fold increase in the
      stimulation index was measured. Synergistic effects of MSCs and peptides were
      observed, with a seven-fold increase in the stimulation index. The results are
      promising and suggest that simultaneous incorporation of MSCs and ECM-derived
      peptides and/or GLP-1 can improve pancreatic islet function in response to
      altered glucose levels in the physiological environment. Copyright (c) 2014 John
      Wiley & Sons, Ltd.

PMID- 25393528
TI  - Effect of latent heat in boiling water on the synthesis of gold nanoparticles of
      different sizes by using the Turkevich method.
AB  - The Turkevich method, involving the reduction of HAuCl4 with citrate in boiling
      water, allows the facile production of monodisperse, quasispherical gold
      nanoparticles (AuNPs). Although, it is well-known that the size of the AuNPs
      obtained with the same recipe vary slightly (as little as approximately 4 nm),
      but noticeably, from one report to another, it has rarely been studied. The
      present work demonstrates that this size variation can be reconciled by the
      small, but noticeable, effect that the latent heat in boiling water has on the
      size of the AuNPs obtained by using the Turkevich method. The increase in latent
      heat during water boiling caused an approximately 3 nm reduction in the size of
      the as-prepared AuNPs; this reduction in size is mainly a result of accelerated
      nucleation driven by the extra heat. It was further demonstrated that, the
      heating temperature can be utilized as an additional measure to adjust the growth
      rate of AuNPs during the reduction of HAuCl4 with citrate in boiling water.
      Therefore, the latent heat of boiling solvents may provide one way to control
      nucleation and growth in the synthesis of monodisperse nanoparticles. 

PMID- 25393527
TI  - Correlates of post-traumatic stress symptoms and growth in cancer patients: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study is to examine the relationships among
      demographic, medical, and psychosocial factors and post-traumatic stress symptoms
      (PTSS) and post-traumatic growth (PTG) in oncology populations. METHOD: A
      systematic search identified k = 116 relevant studies published between 1990 and
      2012. Meta-analyses synthesized results from studies that reported data on
      correlates of PTSS (k = 26) or PTG (k = 48). A meta-analysis was performed for k
      = 5 studies reporting the correlation between PTSS and PTG. RESULTS: Post
      traumatic stress symptoms were associated with depression (r = 0.56), anxiety (r
      = 0.65), distress (r = 0.62), social support (r = -0.33), and physical quality of
      life (r = -0.44). PTG was associated with age (r = -0.08), gender (r = -0.15),
      distress (r = -0.16), depression (r = -0.06), social support (r = 0.30), optimism
      (r = 0.27), positive reappraisal (r = 0.46), spirituality (r = 0.33), and
      religious coping (r = 0.36). There was a small positive relationship between PTSS
      and PTG (r = 0.13). CONCLUSIONS: Post-traumatic stress symptoms and PTG appear to
      be independent constructs, rather than opposite ends of a single dimension. This
      is reflected in a small relationship between these variables and different
      psychosocial correlates. PTSS were strongly associated with variables reflecting
      a general state of negative affect. Optimism, spirituality, and positive coping
      styles were associated with PTG. It remains unclear how they are associated with
      PTSS, given the lack of relevant studies. Longitudinal research is required to
      examine how psychosocial factors influence the relationship between PTSS and PTG.

PMID- 25393529
TI  - Multicolored-fluorescence switching of ICT-type organic solids with clear color
      difference: mechanically controlled excited state.
AB  - A donor-acceptor-type fluorophore containing a twisted diphenylacrylonitrile and
      triphenylamine has been developed by using the Suzuki reaction. The system
      indicates typical intramolecular charge-transfer properties. Upon mechanical
      grinding or hydrostatic pressure, the fluorophore reveals a multicolored
      fluorescence switching. Interestingly, a fluorescence color transition from green
      to red was clearly observed, and the change of photoluminescent (PL) wavelength
      gets close to 111 nm. The mechanisms of high-contrast mechanochromic behavior are
      fully investigated by techniques including powder XRD, PL lifetime, high-pressure
      PL lifetime, and Raman spectra analysis. The tremendous PL wavelength shift is
      attributed to gradual transition of excited states from the local excited state
      to the charge-transfer state.

PMID- 25393530
TI  - Bacterial community structure in Apis florea larvae analyzed by denaturing
      gradient gel electrophoresis and 16S rRNA gene sequencing.
AB  - This study characterizes the colonization and composition of bacterial flora in
      dwarf Asian honeybee (Apis florea) larvae and compares bacterial diversity and
      distribution among different sampling locations. A. florea larvae were collected
      from 3 locations in Chiang Mai province, Thailand. Bacterial DNA was extracted
      from each larva using the phenol-chloroform method. Denaturing gradient gel
      electrophoresis was performed, and the dominant bands were excised from the gels,
      cloned, and sequenced for bacterial species identification. The result revealed
      similarities of bacterial community profiles in each individual colony, but
      differences between colonies from the same and different locations. A. florea
      larvae harbor bacteria belonging to 2 phyla (Firmicutes and Proteobacteria), 5
      classes (Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Bacilli,
      and Clostridia), 6 genera (Clostridium, Gilliamella, Melissococcus,
      Lactobacillus, Saccharibacter, and Snodgrassella), and an unknown genus from
      uncultured bacterial species. The classes with the highest abundance of bacteria
      were Alphaproteobacteria (34%), Bacilli (25%), Betaproteobacteria (11%),
      Gammaproteobacteria (10%), and Clostridia (8%), respectively. Similarly,
      uncultured bacterial species were identified (12%). Environmental bacterial
      species, such as Saccharibacter floricola, were also found. This is the first
      study in which sequences closely related to Melissococcus plutonius, the causal
      pathogen responsible for European foulbrood, have been identified in Thai A.
      florea larvae.

PMID- 25393532
TI  - Total synthesis, stereochemical reassignment, and biological evaluation of (-)
      lyngbyaloside B.
AB  - (-)-Lyngbyaloside B is a 14-membered macrolide glycoside isolated from the marine
      cyanobacterium Lyngbya sp. as a cytotoxic substance by Moore and co-workers. The
      first total synthesis of (-)-lyngbyaloside B and the reassignment of its
      stereostructure is described. The synthesis features an Abiko-Masamune aldol
      reaction, a vinylogous Mukaiyama aldol reaction, and a macrocyclization involving
      an acyl ketene intermediate for the construction of the macrocyclic backbone,
      which contains an acylated tertiary alcohol. The antiproliferative activity of
      selected compounds against a small panel of human cancer cell lines is also
      reported. 

PMID- 25393531
TI  - Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone
      (SIH) analogs: iron chelation, anti-oxidant and cytotoxic properties.
AB  - Salicylaldehyde isonicotinoyl hydrazone (SIH) is a lipophilic, tridentate iron
      chelator with marked anti-oxidant and modest cytotoxic activity against
      neoplastic cells. However, it has poor stability in an aqueous environment due to
      the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a
      series of new SIH analogs (based on previously described aromatic ketones with
      improved hydrolytic stability). Their structure-activity relationships were
      assessed with respect to their stability in plasma, iron chelation efficacy,
      redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells.
      Furthermore, studies assessed the cytotoxicity of these chelators and their
      ability to afford protection against hydrogen peroxide-induced oxidative injury
      in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the
      presence of bulky alkyl substituents near the hydrazone bond, showed severely
      limited biological activity. The introduction of a bromine substituent increased
      ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A
      similar effect was observed when the phenolic ring was exchanged with pyridine
      (i.e., changing the ligating site from O, N, O to N, N, O), which led to pro
      oxidative effects. In contrast, compounds with long, flexible alkyl chains
      adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7
      breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence,
      this study highlights important structure-activity relationships and provides
      insight into the further development of aroylhydrazone iron chelators with more
      potent and selective anti-neoplastic effects. 

PMID- 25393534
TI  - Redesigning a Ministry of Health's organizational structure: exploring
      implementation challenges through Botswana's experiences.
AB  - INTRODUCTION: The Botswana's Ministry of Health redesigned and adopted a new
      organizational structure in 2005, which was poorly implemented. This article
      explores factors that influenced the implementation of this organizational
      structure. METHODS: This article draws from data collected through in-depth
      interviews with 54 purposively selected key informants comprising policy makers,
      senior managers and staff of the Ministry of Health (N = 40) and senior officers
      from various stakeholder organizations (N = 14). FINDINGS: Participants generally
      felt that the review of the Ministry of Health organizational structure was
      important. The previous structure was considered obsolete with fragmented
      functions that limited the overall performance of the health system. The new
      organizational structure was viewed to be aligned to current national priorities
      with potential to positively influence performance. Some key weaknesses
      identified included lack of consultation and information sharing with workers
      during the restructuring process, which affected the understanding of their new
      roles, failure to mobilize key resources to support implementation of the new
      structure and inadequate monitoring of the implementation process. CONCLUSION:
      Redesigning an organizational structure is a major change. There is a need for
      effective and sustained leadership to plan, direct, coordinate, monitor and
      evaluate the implementation phase of the reform. Copyright (c) 2014 John Wiley &
      Sons, Ltd.

PMID- 25393533
TI  - Comparative analysis of predicted plastid-targeted proteomes of sequenced higher
      plant genomes.
AB  - Plastids are actively involved in numerous plant processes critical to growth,
      development and adaptation. They play a primary role in photosynthesis, pigment
      and monoterpene synthesis, gravity sensing, starch and fatty acid synthesis, as
      well as oil, and protein storage. We applied two complementary methods to analyze
      the recently published apple genome (Malus * domestica) to identify putative
      plastid-targeted proteins, the first using TargetP and the second using a custom
      workflow utilizing a set of predictive programs. Apple shares roughly 40% of its
      10,492 putative plastid-targeted proteins with that of the Arabidopsis
      (Arabidopsis thaliana) plastid-targeted proteome as identified by the Chloroplast
      2010 project and ~57% of its entire proteome with Arabidopsis. This suggests that
      the plastid-targeted proteomes between apple and Arabidopsis are different, and
      interestingly alludes to the presence of differential targeting of homologs
      between the two species. Co-expression analysis of 2,224 genes encoding putative
      plastid-targeted apple proteins suggests that they play a role in plant
      developmental and intermediary metabolism. Further, an inter-specific comparison
      of Arabidopsis, Prunus persica (Peach), Malus * domestica (Apple), Populus
      trichocarpa (Black cottonwood), Fragaria vesca (Woodland Strawberry), Solanum
      lycopersicum (Tomato) and Vitis vinifera (Grapevine) also identified a large
      number of novel species-specific plastid-targeted proteins. This analysis also
      revealed the presence of alternatively targeted homologs across species. Two
      separate analyses revealed that a small subset of proteins, one representing 289
      protein clusters and the other 737 unique protein sequences, are conserved
      between seven plastid-targeted angiosperm proteomes. Majority of the novel
      proteins were annotated to play roles in stress response, transport, catabolic
      processes, and cellular component organization. Our results suggest that the
      current state of knowledge regarding plastid biology, preferentially based on
      model systems is deficient. New plant genomes are expected to enable the
      identification of potentially new plastid-targeted proteins that will aid in
      studying novel roles of plastids. 

PMID- 25393535
TI  - Matrix metalloproteinase 9 production by monocytes is enhanced by TNF and
      participates in the pathology of human cutaneous Leishmaniasis.
AB  - INTRODUCTION: Cutaneous leishmaniasis (CL) due to L.braziliensis infection is
      characterized by a strong inflammatory response with high levels of TNF and ulcer
      development. Less attention has been given to the role of mononuclear phagocytes
      to this process. Monocytes constitute a heterogeneous population subdivided into
      classical, intermediate and non-classical, and are known to migrate to
      inflammatory sites and secrete inflammatory mediators. TNF participates in the
      induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades
      basal membrane and its activity is controlled by the tissue inhibitor of
      metalloproteinase. METHODS: Mononuclear cells were obtained from ex-vivo labeling
      sub-populations of monocytes and MMP-9, and the frequency was determined by flow
      cytometry. Culture was performed during 72 hours, stimulating the cells with SLA,
      levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA. RESULTS:
      We observed that cells from CL lesions secrete high amounts of MMP-9 when
      compared to healthy subjects. Although MMP-9 was produced by monocytes, non
      classical ones were the main source of this enzyme. We also observed that TNF
      produced in high level during CL contributes to MMP-9 production. CONCLUSIONS:
      These observations emphasize the role of monocytes, TNF and MMP-9 in the
      pathogenesis of L. braziliensis infection.

PMID- 25393536
TI  - Effect of omega-3 fatty acid ethyl esters on the oxylipin composition of
      lipoproteins in hypertriglyceridemic, statin-treated subjects.
AB  - BACKGROUND: Oxylipins mediate inflammation, vascular tension, and more. Their
      presence in lipoproteins could explain why lipoproteins mediate nearly identical
      activities. METHODS: To determine how oxylipins are distributed in the
      lipoproteins of hypertriglyceridemic subjects, and whether omega-3 fatty acids
      alter them in a manner consistent with improved cardiovascular health, we
      recruited 15 dyslipidemic subjects whose levels of low density lipoprotein
      cholesterol (LDL-C) were at goal but who remained hypertriglyceridemic (200-499
      mg/dL). They were treated them with the indicated dose of 4 g/d omega-3 acid
      ethyl esters (P-OM3) for 8 weeks. Measured oxylipins included mid-chain alcohols
      (HETEs, HEPEs and HDoHEs), ketones (KETEs), epoxides (as EpETrEs, EpETEs, and
      EpDPEs). RESULTS: At baseline, arachidonate-oxylipins (HETEs, KETEs, and EpETrEs)
      were most abundant in plasma with the greatest fraction of total abundance (mean
      |95% CI|) being carried in high density lipoproteins (HDL); 42% |31, 57| followed
      by very low density lipoproteins (VLDL); 27% |20, 36|; and LDL 21% |16, 28|. EPA-
      and DHA-derived oxylipins constituted less than 11% of total. HDL carried
      alcohols and epoxides but VLDL was also rich in ketones. Treatment decreased AA
      derived oxylipins across lipoprotein classes (-23% |-33, -12|, p = 0.0003), and
      expanded EPA-(322% |241, 422|, p<0.0001) and DHA-derived oxylipins (123% |80,
      176|, p<0.0001). CONCLUSIONS: Each lipoprotein class carries a unique oxylipin
      complement. P-OM3 treatment alters the oxylipin content of all classes, reducing
      pro-inflammatory and increasing anti-inflammatory species, consistent with the
      improved inflammatory and vascular status associated with the treatment. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00959842.

PMID- 25393537
TI  - Intramuscular injection of AAV8 in mice and macaques is associated with
      substantial hepatic targeting and transgene expression.
AB  - Intramuscular (IM) administration of adeno-associated viral (AAV) vectors has
      entered the early stages of clinical development with some success, including the
      first approved gene therapy product in the West called Glybera. In preparation
      for broader clinical development of IM AAV vector gene therapy, we conducted
      detailed pre-clinical studies in mice and macaques evaluating aspects of delivery
      that could affect performance. We found that following IM administration of AAV8
      vectors in mice, a portion of the vector reached the liver and hepatic gene
      expression contributed significantly to total expression of secreted transgenes.
      The contribution from liver could be controlled by altering injection volume and
      by the use of traditional (promoter) and non-traditional (tissue-specific
      microRNA target sites) expression control elements. Hepatic distribution of
      vector following IM injection was also noted in rhesus macaques. These pre
      clinical data on AAV delivery should inform safe and efficient development of
      future AAV products. 

PMID- 25393538
TI  - Development of a gene-centered ssr atlas as a resource for papaya (Carica papaya)
      marker-assisted selection and population genetic studies.
AB  - Carica papaya (papaya) is an economically important tropical fruit. Molecular
      marker-assisted selection is an inexpensive and reliable tool that has been
      widely used to improve fruit quality traits and resistance against diseases. In
      the present study we report the development and validation of an atlas of papaya
      simple sequence repeat (SSR) markers. We integrated gene predictions and
      functional annotations to provide a gene-centered perspective for marker-assisted
      selection studies. Our atlas comprises 160,318 SSRs, from which 21,231 were
      located in genic regions (i.e. inside exons, exon-intron junctions or introns). A
      total of 116,453 (72.6%) of all identified repeats were successfully mapped to
      one of the nine papaya linkage groups. Primer pairs were designed for markers
      from 9,594 genes (34.5% of the papaya gene complement). Using papaya-tomato
      orthology assessments, we assembled a list of 300 genes (comprising 785 SSRs)
      potentially involved in fruit ripening. We validated our atlas by screening 73
      SSR markers (including 25 fruit ripening genes), achieving 100% amplification
      rate and uncovering 26% polymorphism rate between the parental genotypes (Sekati
      and JS12). The SSR atlas presented here is the first comprehensive gene-centered
      collection of annotated and genome positioned papaya SSRs. These features
      combined with thousands of high-quality primer pairs make the atlas an important
      resource for the papaya research community. 

PMID- 25393539
TI  - Genetic control of startle behavior in medaka fish.
AB  - Genetic polymorphisms are thought to generate intraspecific behavioral
      diversities, both within and among populations. The mechanisms underlying genetic
      control of behavioral properties, however, remain unclear in wild-type
      vertebrates, including humans. To explore this issue, we used diverse inbred
      strains of medaka fish (Oryzias latipes) established from the same and different
      local populations. Medaka exhibit a startle response to a visual stimulus
      (extinction of illumination) by rapidly bending their bodies (C-start) 20-ms
      after the stimulus presentation. We measured the rates of the response to
      repeated stimuli (1-s interval, 40 times) among four inbred strains, HNI-I, HNI
      II, HO5, and Hd-rR-II1, and quantified two properties of the startle response:
      sensitivity (response rate to the first stimulus) and attenuation of the response
      probability with repeated stimulus presentation. Among the four strains, the
      greatest differences in these properties were detected between HNI-II and Hd-rR
      II1. HNI-II exhibited high sensitivity (approximately 80%) and no attenuation,
      while Hd-rR-II1 exhibited low sensitivity (approximately 50%) and almost complete
      attenuation after only five stimulus presentations. Our findings suggested
      behavioral diversity of the startle response within a local population as well as
      among different populations. Linkage analysis with F2 progeny between HNI-II and
      Hd-rR-II1 detected quantitative trait loci (QTL) highly related to attenuation,
      but not to sensitivity, with a maximum logarithm of odds score of 11.82 on
      linkage group 16. The three genotypes (homozygous for HNI-II and Hd-rR-II1
      alleles, and heterozygous) at the marker nearest the QTL correlated with
      attenuation. Our findings are the first to suggest that a single genomic region
      might be sufficient to generate individual differences in startle behavior
      between wild-type strains. Further identification of genetic polymorphisms that
      define the behavioral trait will contribute to our understanding of the neural
      mechanisms underlying behavioral diversity, allowing us to investigate the
      adaptive significance of intraspecific behavioral polymorphisms of the startle
      response. 

PMID- 25393541
TI  - Allowing for uncertainty due to missing continuous outcome data in pairwise and
      network meta-analysis.
AB  - Missing outcome data are commonly encountered in randomized controlled trials and
      hence may need to be addressed in a meta-analysis of multiple trials. A common
      and simple approach to deal with missing data is to restrict analysis to
      individuals for whom the outcome was obtained (complete case analysis). However,
      estimated treatment effects from complete case analyses are potentially biased if
      informative missing data are ignored. We develop methods for estimating meta
      analytic summary treatment effects for continuous outcomes in the presence of
      missing data for some of the individuals within the trials. We build on a method
      previously developed for binary outcomes, which quantifies the degree of
      departure from a missing at random assumption via the informative missingness
      odds ratio. Our new model quantifies the degree of departure from missing at
      random using either an informative missingness difference of means or an
      informative missingness ratio of means, both of which relate the mean value of
      the missing outcome data to that of the observed data. We propose estimating the
      treatment effects, adjusted for informative missingness, and their standard
      errors by a Taylor series approximation and by a Monte Carlo method. We apply the
      methodology to examples of both pairwise and network meta-analysis with multi-arm
      trials.

PMID- 25393540
TI  - Dll4 blockade potentiates the anti-tumor effects of VEGF inhibition in renal cell
      carcinoma patient-derived xenografts.
AB  - BACKGROUND: The Notch ligand Delta-like 4 (Dll4) is highly expressed in vascular
      endothelium and has been shown to play a pivotal role in regulating tumor
      angiogenesis. Blockade of the Dll4-Notch pathway in preclinical cancer models has
      been associated with non-productive angiogenesis and reduced tumor growth. Given
      the cross-talk between the vascular endothelial growth factor (VEGF) and Delta
      Notch pathways in tumor angiogenesis, we examined the activity of a function
      blocking Dll4 antibody, REGN1035, alone and in combination with anti-VEGF therapy
      in renal cell carcinoma (RCC). METHODS AND RESULTS: Severe combined
      immunodeficiency (SCID) mice bearing patient-derived clear cell RCC xenografts
      were treated with REGN1035 and in combination with the multi-targeted tyrosine
      kinase inhibitor sunitinib or the VEGF blocker ziv-aflibercept.
      Immunohistochemical and immunofluorescent analyses were carried out, as well as
      magnetic resonance imaging (MRI) examinations pre and 24 hours and 2 weeks post
      treatment. Single agent treatment with REGN1035 resulted in significant tumor
      growth inhibition (36-62%) that was equivalent to or exceeded the single agent
      anti-tumor activity of the VEGF pathway inhibitors sunitinib (38-54%) and ziv
      aflibercept (46%). Importantly, combination treatments with REGN1035 plus VEGF
      inhibitors resulted in enhanced anti-tumor effects (72-80% growth inhibition),
      including some tumor regression. Magnetic resonance imaging showed a marked
      decrease in tumor perfusion in all treatment groups. Interestingly, anti-tumor
      efficacy of the combination of REGN1035 and ziv-aflibercept was also observed in
      a sunitinib resistant ccRCC model. CONCLUSIONS: Overall, these findings
      demonstrate the potent anti-tumor activity of Dll4 blockade in RCC patient
      derived tumors and a combination benefit for the simultaneous targeting of the
      Dll4 and VEGF signaling pathways, highlighting the therapeutic potential of this
      treatment modality in RCC.

PMID- 25393542
TI  - Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population,
      livestock and ticks in Kosovo.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is an acute, tick borne disease often
      associated with hemorrhagic presentations and high case fatality rate. Kosovo is
      a highly endemic area for CCHF, with a significant case fatality rate. The aim of
      our study was to determine the prevalence of CCHF in Kosovo. We tested 1105 serum
      samples from healthy population in both endemic and non-endemic areas in the
      country. Our results revealed a seroprevalence of 4.0% (range 0-9.3%) which is
      comparable to the seroprevalence in other countries. We show that seroprevalence
      is correlated to the disease incidence in each studied municipality. We also
      tested 401 animal sera (353 cow, 30 sheep, 10 goat and 8 chicken) in four endemic
      municipalities in Kosovo. We detected specific antibodies in all animals except
      in chicken. Seroprevalence in cows is comparable to other endemic areas and
      correlates to the seroprevalence in humans. No CCHF RNA could be detected in 105
      tick samples obtained in 2012 and 2013. Sequencing of CCHFV positive ticks from
      2001 revealed that the virus is most closely related to viral strains that were
      detected in CCHF patients from Kosovo. Results suggest that mild CCHF cases are
      most probably underdiagnosed and consequently that the burden of disease is
      higher than reported. Our study provides key information for CCHF surveillance
      and raises awareness for possible imported cases in CCHF non-endemic countries. 

PMID- 25393543
TI  - Differentiation between primary cerebral lymphoma and glioblastoma using the
      apparent diffusion coefficient: comparison of three different ROI methods.
AB  - OBJECTIVE: Apparent diffusion coefficients (ADC) can help differentiate between
      central nervous system (CNS) lymphoma and Glioblastoma (GBM). However, overlap
      between ADCs for GBM and lymphoma have been reported because of various region of
      interest (ROI) methods. Our aim is to explore ROI method to provide the most
      reproducible results for differentiation. MATERIALS AND METHODS: We studied 25
      CNS lymphomas and 62 GBMs with three ROI methods: (1) ROI1, whole tumor volume;
      (2) ROI2, multiple ROIs; and (3) ROI3, a single ROI. Interobserver variability of
      two readers for each method was analyzed by intraclass correlation(ICC). ADCs
      were compared between GBM and lymphoma, using two-sample t-test. The
      discriminative ability was determined by ROC analysis. RESULTS: ADCs from ROI1
      showed most reproducible results (ICC >0.9). For ROI1, ADCmean for lymphoma
      showed significantly lower values than GBM (p = 0.03). The optimal cut-off value
      was 0.98*10(-3) mm2/s with 85% sensitivity and 90% specificity. For ROI2, ADCmin
      for lymphoma was significantly lower than GBM (p = 0.02). The cut-off value was
      0.69*10(-3) mm2/s with 87% sensitivity and 88% specificity. CONCLUSION: ADC
      values were significantly dependent on ROI method. ADCs from the whole tumor
      volume had the most reproducible results. ADCmean from the whole tumor volume may
      aid in differentiating between lymphoma and GBM. However, multi-modal imaging
      approaches are recommended than ADC alone for differentiation.

PMID- 25393544
TI  - Negation's not solved: generalizability versus optimizability in clinical natural
      language processing.
AB  - A review of published work in clinical natural language processing (NLP) may
      suggest that the negation detection task has been "solved." This work proposes
      that an optimizable solution does not equal a generalizable solution. We
      introduce a new machine learning-based Polarity Module for detecting negation in
      clinical text, and extensively compare its performance across domains. Using four
      manually annotated corpora of clinical text, we show that negation detection
      performance suffers when there is no in-domain development (for manual methods)
      or training data (for machine learning-based methods). Various factors (e.g.,
      annotation guidelines, named entity characteristics, the amount of data, and
      lexical and syntactic context) play a role in making generalizability difficult,
      but none completely explains the phenomenon. Furthermore, generalizability
      remains challenging because it is unclear whether to use a single source for
      accurate data, combine all sources into a single model, or apply domain
      adaptation methods. The most reliable means to improve negation detection is to
      manually annotate in-domain training data (or, perhaps, manually modify rules);
      this is a strategy for optimizing performance, rather than generalizing it. These
      results suggest a direction for future work in domain-adaptive and task-adaptive
      methods for clinical NLP. 

PMID- 25393545
TI  - War and infectious diseases: challenges of the Syrian civil war.

PMID- 25393546
TI  - Quantitative analysis of tissue distribution of the B16BL6-derived exosomes using
      a streptavidin-lactadherin fusion protein and iodine-125-labeled biotin
      derivative after intravenous injection in mice.
AB  - We previously succeeded in the visualization of tissue distribution of B16BL6
      cells-derived exosomes by labeling with Gaussia luciferase (gLuc)-LA, a fusion
      protein of gLuc (a reporter protein) and lactadherin (LA; an exosome-tropic
      protein). However, total amount of B16BL6-derived exosomes delivered to each
      organ could not be evaluated because of the reduction of luminescent signal from
      gLuc-LA. The aim of the present study was to quantitatively evaluate the tissue
      distribution of B16BL6-derived exosomes. To this end, we labeled B16BL6-derived
      exosomes with iodine-125 ((125) I) based on streptavidin (SAV)-biotin system. A
      plasmid vector encoding fusion protein, SAV-LA, was constructed, and B16BL6 cells
      were transfected with the plasmid to obtain SAV-LA-coupled exosomes. SAV-LA
      coupled exosomes were incubated with (3-(125) I-iodobenzoyl) norbiotinamide
      ((125) I-IBB) to obtain (125) I-labeled B16BL6 exosomes. After intravenous
      injection of (125) I-labeled B16BL6 exosomes into mice, radioactivity quickly
      disappeared from the blood circulation. At 4 h, 28%, 1.6%, and 7% of the injected
      radioactivity/organ was detected in the liver, spleen, and lung, respectively.
      These results indicate that (125) I-labeling of exosomes using SAV-biotin system
      is a useful method to quantitatively evaluate the amount of exogenously
      administered exosomes delivered to each organ and that the liver is the major
      organ in the clearance of exogenously administered B16BL6-derived exosomes.

PMID- 25393547
TI  - Young children's difficulty with indirect speech acts: implications for
      questioning child witnesses.
AB  - Prior research suggests that infelicitous choice of questions can significantly
      underestimate children's actual abilities, independently of suggestiveness. One
      possibly difficult question type is indirect speech acts such as "Do you know..."
      questions (DYK, e.g., "Do you know where it happened?"). These questions directly
      ask if respondents know, while indirectly asking what respondents know. If
      respondents answer "yes," but fail to elaborate, they are either ignoring or
      failing to recognize the indirect question (known as pragmatic failure). Two
      studies examined the effect of indirect speech acts on maltreated and non
      maltreated 2- to 7-year-olds' post-event interview responses. Children were read
      a story and later interviewed using DYK and Wh- questions. Additionally, children
      completed a series of executive functioning tasks. Both studies revealed that
      using DYK questions increased the chances of pragmatic failure, particularly for
      younger children and those with lower inhibitory control skills.

PMID- 25393548
TI  - Spinal mechanisms may provide a combination of intermittent and continuous
      control of human posture: predictions from a biologically based
      neuromusculoskeletal model.
AB  - Several models have been employed to study human postural control during upright
      quiet stance. Most have adopted an inverted pendulum approximation to the
      standing human and theoretical models to account for the neural feedback
      necessary to keep balance. The present study adds to the previous efforts in
      focusing more closely on modelling the physiological mechanisms of important
      elements associated with the control of human posture. This paper studies
      neuromuscular mechanisms behind upright stance control by means of a biologically
      based large-scale neuromusculoskeletal (NMS) model. It encompasses: i)
      conductance-based spinal neuron models (motor neurons and interneurons); ii)
      muscle proprioceptor models (spindle and Golgi tendon organ) providing sensory
      afferent feedback; iii) Hill-type muscle models of the leg plantar and
      dorsiflexors; and iv) an inverted pendulum model for the body biomechanics during
      upright stance. The motor neuron pools are driven by stochastic spike trains.
      Simulation results showed that the neuromechanical outputs generated by the NMS
      model resemble experimental data from subjects standing on a stable surface.
      Interesting findings were that: i) an intermittent pattern of muscle activation
      emerged from this posture control model for two of the leg muscles (Medial and
      Lateral Gastrocnemius); and ii) the Soleus muscle was mostly activated in a
      continuous manner. These results suggest that the spinal cord anatomy and
      neurophysiology (e.g., motor unit types, synaptic connectivities, ordered
      recruitment), along with the modulation of afferent activity, may account for the
      mixture of intermittent and continuous control that has been a subject of debate
      in recent studies on postural control. Another finding was the occurrence of the
      so-called "paradoxical" behaviour of muscle fibre lengths as a function of
      postural sway. The simulations confirmed previous conjectures that reciprocal
      inhibition is possibly contributing to this effect, but on the other hand showed
      that this effect may arise without any anticipatory neural control mechanism. 

PMID- 25393549
TI  - Analysis of young children's abilities to cluster and switch during a verbal
      fluency task.
AB  - To investigate developmental changes that take place in verbal fluency (VF)
      performance during early childhood, a VF task was administered to 225 healthy,
      Dutch-speaking children aged between 4.14 and 6.89 years. Three categories of VF
      outcome measures were included: i.e., word productivity, mean cluster size, and
      number of switches. Age influenced performance on all VF outcome measures
      linearly; i.e., older children produced more words, made longer clusters, and
      switched more. Higher levels of intelligence were associated with increased VF
      word productivity, but not with measures of switching and clustering. When
      leaving intelligence out of these analyses, we additionally found an interaction
      between level of parental education (LPE) and sex on total word productivity,
      i.e., girls with parents who had lower LPE produced fewer words than the other
      children. Furthermore, a similar interaction of LPE and sex was found for the
      number of switches: i.e., girls who had parents with lower LPE made fewer
      switches than the other children. Findings suggest that even in 4 to 6-year-old
      children important changes take place over time in VF and in processes underlying
      successful performance. Attention should be paid to age-extrinsic factors, such
      as LPE and sex, since these have been found to influence VF performance in young
      children. 

PMID- 25393551
TI  - The successful merger of theoretical thermochemistry with fragment-based methods
      in quantum chemistry.
AB  - CONSPECTUS: Quantum chemistry and electronic structure theory have proven to be
      essential tools to the experimental chemist, in terms of both a priori
      predictions that pave the way for designing new experiments and rationalizing
      experimental observations a posteriori. Translating the well-established success
      of electronic structure theory in obtaining the structures and energies of small
      chemical systems to increasingly larger molecules is an exciting and ongoing
      central theme of research in quantum chemistry. However, the prohibitive
      computational scaling of highly accurate ab initio electronic structure methods
      poses a fundamental challenge to this research endeavor. This scenario
      necessitates an indirect fragment-based approach wherein a large molecule is
      divided into small fragments and is subsequently reassembled to compute its
      energy accurately. In our quest to further reduce the computational expense
      associated with the fragment-based methods and overall enhance the applicability
      of electronic structure methods to large molecules, we realized that the broad
      ideas involved in a different area, theoretical thermochemistry, are transferable
      to the area of fragment-based methods. This Account focuses on the effective
      merger of these two disparate frontiers in quantum chemistry and how new concepts
      inspired by theoretical thermochemistry significantly reduce the total number of
      electronic structure calculations needed to be performed as part of a fragment
      based method without any appreciable loss of accuracy. Throughout, the
      generalized connectivity based hierarchy (CBH), which we developed to solve a
      long-standing problem in theoretical thermochemistry, serves as the linchpin in
      this merger. The accuracy of our method is based on two strong foundations: (a)
      the apt utilization of systematic and sophisticated error-canceling schemes via
      CBH that result in an optimal cutting scheme at any given level of fragmentation
      and (b) the use of a less expensive second layer of electronic structure method
      to recover all the missing long-range interactions in the parent large molecule.
      Overall, the work featured here dramatically decreases the computational expense
      and empowers the execution of very accurate ab initio calculations (gold-standard
      CCSD(T)) on large molecules and thereby facilitates sophisticated electronic
      structure applications to a wide range of important chemical problems.

PMID- 25393550
TI  - Evolution of DNA methylation patterns in the Brassicaceae is driven by
      differences in genome organization.
AB  - DNA methylation is an ancient molecular modification found in most eukaryotes. In
      plants, DNA methylation is not only critical for transcriptionally silencing
      transposons, but can also affect phenotype by altering expression of protein
      coding genes. The extent of its contribution to phenotypic diversity over
      evolutionary time is, however, unclear, because of limited stability of
      epialleles that are not linked to DNA mutations. To dissect the relative
      contribution of DNA methylation to transposon surveillance and host gene
      regulation, we leveraged information from three species in the Brassicaceae that
      vary in genome architecture, Capsella rubella, Arabidopsis lyrata, and
      Arabidopsis thaliana. We found that the lineage-specific expansion and
      contraction of transposon and repeat sequences is the main driver of
      interspecific differences in DNA methylation. The most heavily methylated
      portions of the genome are thus not conserved at the sequence level. Outside of
      repeat-associated methylation, there is a surprising degree of conservation in
      methylation at single nucleotides located in gene bodies. Finally, dynamic DNA
      methylation is affected more by tissue type than by environmental differences in
      all species, but these responses are not conserved. The majority of DNA
      methylation variation between species resides in hypervariable genomic regions,
      and thus, in the context of macroevolution, is of limited phenotypic consequence.

PMID- 25393553
TI  - Argentophilic interactions.
AB  - The decade 1990-2000 saw a growing interest in aurophilic interactions in gold
      chemistry. These interactions were found to influence significantly a variety of
      structural and other physical characteristics of gold(I) compounds. The attention
      paid to this unusual and counterintuitive type of intra- and intermolecular
      bonding between seemingly closed-shell metal centers has rapidly been extended to
      also include silver chemistry. Hundreds of experimental and computational studies
      have since been dedicated to the argentophilicity phenomenon. The results of this
      development are reviewed herein focusing on molecular systems where two or more
      silver(I) centers are in close contact leading to specific structural
      characteristics and a variety of novel physical properties. These include
      strongly modified ligand-to-metal charge-transfer processes observed in
      absorption and emission spectroscopy, but also colossal positive and negative
      thermal expansion on the one hand and unprecedented negative linear
      compressibility of crystal parameters on the other. 

PMID- 25393552
TI  - Isolation and genotyping of acanthamoeba strains from soil sources from Jamaica,
      West Indies.
AB  - Acanthamoeba spp. are opportunistic pathogens that are ubiquitous in nature. Many
      species of this genus are responsible for a fatal encephalitis and keratitis in
      humans and other animals. Seventy-two soil samples were collected from the
      parishes across Jamaica and assessed for the presence of Acanthamoeba spp.
      Cultivation was carried out on non-nutrient agar plates seeded with heat killed
      Escherichia coli. PCR and sequencing of the DF3 region were carried out in order
      to genotype the isolated strains of Acanthamoeba. Thermotolerance and
      osmotolerance assays were utilized to investigate the pathogenic potential of the
      Acanthamoeba isolates. Acanthamoeba spp. was isolated from 63.9% of soil samples.
      Sequencing of the DF3 region of the 18S rDNA resulted in the identification of
      genotypes T4, T5, and T11. T4 genotype was most frequently isolated. Most
      isolates were thermotolerant or both thermotolerant and osmotolerant, indicating
      that they may present the potential to cause disease in humans and other animals.

PMID- 25393554
TI  - Quantifying the impact of development on phenotypic variation and evolution.
AB  - A primary goal of evolutionary biology is to identify the factors that shape
      phenotypic evolution. According to the theory of natural selection, phenotypic
      evolution occurs through the differential survival and reproduction of
      individuals whose traits are selectively advantageous relative to other
      individuals in the population. This implies that evolution by natural selection
      is contingent upon the distribution and magnitude of phenotypic variation among
      individuals, which are in turn the products of developmental processes.
      Development therefore has the potential to affect the trajectory and rate of
      phenotypic evolution. Recent research in diverse systems (e.g., mammalian teeth,
      cichlid skulls, butterfly wings, and marsupial limbs) supports the hypothesis
      that development biases phenotypic variation and evolution, but suggests that
      these biases might be system-specific.

PMID- 25393556
TI  - Influence of inspiratory flow pattern and nebulizer position on aerosol delivery
      with a vibrating-mesh nebulizer during invasive mechanical ventilation: an in
      vitro analysis.
AB  - BACKGROUND: Aerosol delivery during invasive mechanical ventilation (IMV) depends
      on nebulizer type, placement of the nebulizer and ventilator settings. The
      purpose of this study was to determine the influence of two inspiratory flow
      patterns on amikacin delivery with a vibrating-mesh nebulizer placed at different
      positions on an adult lung model of IMV equipped with a proximal flow sensor
      (PFS). METHODS: IMV was simulated using a ventilator connected to a lung model
      through an 8-mm inner-diameter endotracheal tube. The impact of a decelerating
      and a constant flow pattern on aerosol delivery was evaluated in volume
      controlled mode (tidal volume 500 mL, 20 breaths/min, inspiratory time of 1 sec,
      bias flow of 10 L/min). An amikacin solution (250 mg/3 mL) was nebulized with
      Aeroneb Solo((r)) placed at five positions on the ventilator circuit equipped
      with a PFS: connected to the endotracheal tube (A), to the Y-piece (B), placed at
      15 cm (C) and 45 cm upstream of the Y-piece (D), and placed at 15 cm of the
      inspiratory outlet of the ventilator (E). The four last positions were also
      tested without PFS. Deposited doses of amikacin were measured using the
      gravimetric residual method. RESULTS: Amikacin delivery was significantly reduced
      with a decelerating inspiratory flow pattern compared to a constant flow
      (p<0.05). With a constant inspiratory flow pattern, connecting the nebulizer to
      the endotracheal tube enabled similar deposited doses than these obtained when
      connecting the nebulizer close to the ventilator. The PFS reduced deposited doses
      only when the nebulizer was connected to the Y-piece with both flow patterns or
      placed at 15 cm of the Y-piece with a constant inspiratory flow (p<0.01).
      CONCLUSIONS: Using similar tidal volume and inspiratory time, a constant flow
      pattern (30 L/min) delivers a higher amount of amikacin through an endotracheal
      tube compared to a decelerating inspiratory flow pattern (peak inspiratory flow
      around 60 L/min). The optimal nebulizer position depends on the inspiratory flow
      pattern and the presence of a PFS.

PMID- 25393558
TI  - Who says population health is a long-term game? 100-day projects can generate
      short-term results for at-risk groups.

PMID- 25393557
TI  - Design and synthesis of highly potent and isoform selective JNK3 inhibitors: SAR
      studies on aminopyrazole derivatives.
AB  - The c-jun N-terminal kinase 3 (JNK3) is expressed primarily in the brain.
      Numerous reports have shown that inhibition of JNK3 is a promising strategy for
      treatment of neurodegeneration. The optimization of aminopyrazole-based JNK3
      inhibitors with improved potency, isoform selectivity, and pharmacological
      properties by structure-activity relationship (SAR) studies utilizing biochemical
      and cell-based assays, and structure-based drug design is reported. These
      inhibitors had high selectivity over JNK1 and p38alpha, minimal cytotoxicity,
      potent inhibition of 6-OHDA-induced mitochondrial membrane potential dissipation
      and ROS generation, and good drug metabolism and pharmacokinetic (DMPK)
      properties for iv dosing. 26n was profiled against 464 kinases and was found to
      be highly selective hitting only seven kinases with >80% inhibition at 10 MUM.
      Moreover, 26n showed good solubility, good brain penetration, and good DMPK
      properties. Finally, the crystal structure of 26k in complex with JNK3 was solved
      at 1.8 A to explore the binding mode of aminopyrazole based JNK3 inhibitors. 

PMID- 25393559
TI  - Functional characterization of CCR in birch (Betula platyphylla * Betula pendula)
      through overexpression and suppression analysis.
AB  - We cloned a Cinnamoyl-CoA Reductase gene (BpCCR1) from an apical meristem and
      first internode of Betula platyphylla and characterized its functions in lignin
      biosynthesis, wood formation and tree growth through transgenic approaches. We
      generated overexpression and suppression transgenic lines and analyzed them in
      comparison with the wild-type in terms of lignin content, anatomical
      characteristics, height and biomass. We found that BpCCR1 overexpression could
      increase lignin content up to 14.6%, and its underexpression decreased lignin
      content by 6.3%. Surprisingly, modification of BpCCR1 expression led to
      conspicuous changes in wood characteristics, including xylem vessel number and
      arrangement, and secondary wall thickness. The growth of transgenic trees in
      terms of height was also significantly influenced by the modification of BpCCR1
      genes. We discuss the functions of BpCCR1 in the context of a phylogenetic tree
      built with CCR genes from multiple species. 

PMID- 25393560
TI  - Proteome folding kinetics is limited by protein halflife.
AB  - How heterogeneous are proteome folding timescales and what physical principles,
      if any, dictate its limits? We answer this by predicting copy number weighted
      folding speed distribution - using the native topology - for E.coli and Yeast
      proteome. E.coli and Yeast proteomes yield very similar distributions with
      average folding times of 100 milliseconds and 170 milliseconds, respectively. The
      topology-based folding time distribution is well described by a diffusion-drift
      mutation model on a flat-fitness landscape in free energy barrier between two
      boundaries: i) the lowest barrier height determined by the upper limit of folding
      speed and ii) the highest barrier height governed by the lower speed limit of
      folding. While the fastest time scale of the distribution is near the
      experimentally measured speed limit of 1 microsecond (typical of barrier-less
      folders), we find the slowest folding time to be around seconds ([Formula: see
      text]8 seconds for Yeast distribution), approximately an order of magnitude less
      than the fastest halflife (approximately 2 minutes) in the Yeast proteome. This
      separation of timescale implies even the fastest degrading protein will have
      moderately high (96%) probability of folding before degradation. The overall
      agreement with the flat-fitness landscape model further hints that proteome
      folding times did not undergo additional major selection pressures - to make
      proteins fold faster - other than the primary requirement to "sufficiently beat
      the clock" against its lifetime. Direct comparison between the predicted folding
      time and experimentally measured halflife further shows 99% of the proteome have
      a folding time less than their corresponding lifetime. These two findings
      together suggest that proteome folding kinetics may be bounded by protein
      halflife. 

PMID- 25393561
TI  - Follicle-stimulating hormone promotes age-related endometrial atrophy through
      cross-talk with transforming growth factor beta signal transduction pathway.
AB  - It is widely believed that endometrial atrophy in postmenopausal women is due to
      an age-related reduction in estrogen level. But the role of high circulating
      follicle-stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here,
      we explored the role of high circulating FSH in physiological endometrial
      atrophy. We found that FSH exacerbated post-OVX endometrial atrophy in mice, and
      this effect was ameliorated by lowering FSH with Gonadotrophin-releasing hormone
      agonist (GnRHa). In vitro, FSH inhibited endometrial proliferation and promoted
      the apoptosis of primary cultured endometrial cells in a dose-dependent manner.
      In addition, upregulation of caspase3, caspase8, caspase9, autophagy-related
      proteins (ATG3, ATG5, ATG7, ATG12 and LC3) and downregulation of c-Jun were also
      observed in endometrial adenocytes. Furthermore, smad2 and smad3 showed a time
      dependent activation in endometrial cells which can be partly inhibited by
      blocking the transforming growth factor beta receptor II (TbetaRII). In
      conclusion, FSH regulated endometrial atrophy by affecting the proliferation,
      autophagy and apoptosis of endometrial cells partly through activation of the
      transforming growth factor beta (TGFbeta) pathway. 

PMID- 25393562
TI  - Accumulation of amorphous Cr(III)-Te(IV) nanoparticles on the surface of
      Shewanella oneidensis MR-1 through reduction of Cr(VI).
AB  - Industrial effluents constitute a major source of metal pollution of aquatic
      bodies. Moreover, due to their environmental persistence, toxic metal pollution
      is of special concern. Microbial reduction is considered a promising strategy for
      toxic metal removal among the several methods available for metal remediation.
      Here, we describe the coremediation of toxic Cr(VI) and Te(IV) by the
      dissimilatory metal reducing bacterium-Shewanella oneidensis MR-1. In the
      presence of both Cr(VI) and Te(IV), S. oneidensis MR-1 reduced Cr(VI) to the less
      toxic Cr(III) form, but not Te(IV) to Te(0). The reduced Cr(III) ions complexed
      rapidly with Te(IV) ions and were precipitated from the cell cultures. Electron
      microscopic analyses revealed that the Cr-Te complexed nanoparticles localized on
      the bacterial outer membranes. K-edge X-ray absorption spectrometric analyses
      demonstrated that Cr(III) produced by S. oneidensis MR-1 was rapidly complexed
      with Te(IV) ions, followed by formation of amorphous Cr(III)-Te(IV) nanoparticles
      on the cell surface. Our results could be applied for the simultaneous
      sequestration and detoxification of both Cr(VI) and Te(IV) as well as for the
      preparation of nanomaterials through environmental friendly processes.

PMID- 25393563
TI  - Obesity, adipokines and cancer: an update.
AB  - Obesity causes dysfunction of adipose tissue, with resultant chronic inflammation
      and adverse interplay of various adipokines, sex steroids and endocrine hormones.
      All these drive tumourigenesis and explain the epidemiological link between
      obesity and cancer. Over the past decade, the associations among obesity,
      adipokines and cancer have been increasingly recognized. Adipokines and their
      respective signalling pathways have drawn much research attention in the field of
      oncology and cancer therapeutics. This review will discuss the recent advances in
      the understanding of the association of several adipokines with common obesity
      related cancers and the clinical therapeutic implications. 

PMID- 25393564
TI  - A formula for human average whole-body SARwb under diffuse fields exposure in the
      GHz region.
AB  - A simple formula to determine the human average whole-body SAR (SAR(wb)) under
      realistic propagation conditions is proposed in the GHz region, i.e. from 1.45
      GHz to 5.8 GHz. The methodology is based on simulations of ellipsoidal human body
      models. Only the exposure (incident power densities) and the human mass are
      needed to apply the formula. Diffuse scattered illumination is addressed for the
      first time and the possible presence of a Line-of-Sight (LOS) component is
      addressed as well. As validation, the formula is applied to calculate the average
      whole-body SAR(wb) in 3D heterogeneous phantoms, i.e. the virtual family (34 year
      old male, 26 year-old female, 11 year-old girl, and 6 year-old boy) and the
      results are compared with numerical ones--using the Finite-Difference Time-Domain
      (FDTD) method--at 3 GHz. For the LOS exposure, the average relative error varies
      from 28% to 12% (resp. 14-12%) for the vertical polarization (resp. horizontal
      polarization), depending on the heteregeneous phantom. Regarding the diffuse
      illumination, relative errors of -39.40%, -11.70%, 10.70%, and 10.60% are
      obtained for the 6 year-old boy, 11 year-old girl, 26 year-old female, and 34
      year-old male, respectively. The proposed formula estimates well (especially for
      adults) the SAR(wb) induced by diffuse illumination in realistic conditions. In
      general, the correctness of the formula improves when the human mass increases.
      Keeping the uncertainties of the FDTD simulations in mind, the proposed formula
      might be important for the dosimetry community to assess rapidly and accurately
      the human absorption of electromagnetic radiation caused by diffuse fields in the
      GHz region. Finally, we show the applicability of the proposed formula to
      personal dosimetry for epidemiological research.

PMID- 25393565
TI  - The association between the polymorphisms in a sodium channel gene SCN7A and
      essential hypertension: a case-control study in the Northern Han Chinese.
AB  - Nax , an alpha-subunit of the sodium channel encoded by the SCN7A gene, has been
      deemed to be a sensor of the concentration of sodium in the brain and may be
      involved in salt intake behavior. We inferred that Nax /SCN7A may participate in
      the regulation of blood pressure and the pathogenesis of essential hypertension
      (EH). The present case-control study involving 615 hypertensives and 617
      normotensives was performed to investigate the association between SCN7A
      polymorphisms and EH in the Northern Han Chinese population. The three common
      single nucleotide polymorphisms (SNPs) (rs3791251, rs6738031, rs7565062) in the
      exons of SCN7A were genotyped with the TaqMan assay. Significant association
      between SNP rs7565062 and EH was found under the addictive and dominant genetic
      models (P = 0.024, OR = 1.283, 95%CI [1.033-1.592]; P = 0.013, OR = 1.203, 95%CI
      [1.040-1.392]; respectively). The three SNPs were in close pair-wise linkage
      disequilibrium with each other and the haplotype analyses indicated that
      haplotype G-A-T was significantly associated with increased risk of EH (P =
      0.023, OR = 1.290). In conclusion, our data showed that SNP rs7565062 of SCN7A
      was significantly associated with EH and the allele T of rs7565062 or the related
      haplotype G-A-T will be a genetic risk factor for EH in the Northern Han Chinese
      population. 

PMID- 25393566
TI  - Is Prone Position Ideal for Manipulation and Pinning of Displaced Pediatric
      Extension-type Supracondylar Fractures of Humerus? A Randomized Control Trial.
AB  - BACKGROUND: Closed reduction and percutaneous pin fixation is the standard of
      care for displaced supracondylar fractures of humerus in children. Although it is
      routinely performed in supine position, some authors recommend prone position to
      be advantageous as it aids in gravity reduction and avoids elbow hyperflexion.
      This study was conducted to compare the ease of manipulation and pinning,
      clinical, and radiologic outcomes in supine versus prone position. METHODS: Fifty
      two children with acute, grade III supracondylar humerus fractures without
      vascular injury were included in the study. They were grouped into prone (n=26)
      and supine (n=26) based on computer-generated block randomization. The duration
      of procedure, number of radiation exposures, attempts at closed reduction, and
      attempts at placing the pins were analyzed. Functional and radiologic outcomes
      were assessed for a minimum follow-up of 1 year. RESULTS: There was no
      significant difference between the 2 groups in the duration of procedure
      (P=0.422), number of radiation exposure (P=0.470), attempts at closed reduction
      (P=0.904), and attempts for pinning (P=0.745) and the final clinical and
      radiologic outcomes. One patient in prone group had cubitus varus of 8 degrees.
      Functionally, 2 in the supine group and 3 in prone group had poor outcomes.
      CONCLUSIONS: There is no significant difference in the ease of reduction and
      pinning between supine and prone positions. Grossly displaced fractures with skin
      puckering are difficult to manipulate in prone position. Supine position is ideal
      for closed reduction and pinning of all patterns of type III supracondylar
      fractures.

PMID- 25393567
TI  - Results of Displaced Pediatric Tibial Spine Fractures: A Comparison Between Open,
      Arthroscopic, and Closed Management.
AB  - BACKGROUND: Displaced tibial spine fractures are frequently treated with surgical
      reduction and fixation, but no comparison studies have been performed. This study
      was undertaken to compare fragment reduction and adverse outcomes between open
      arthrotomy [open reduction and internal fixation (ORIF)], arthroscopy
      [arthroscopic-assisted internal fixation (AAIF)], and closed management [closed
      management and casting (CMC)] of pediatric tibial spine fractures. METHODS: A
      retrospective review of children treated for displaced tibial spine fractures
      from 2003 to 2011 was performed after categorizing into the 3 treatment groups.
      Demographics, mechanism of injury, radiographic measures (plain film and computed
      tomography), treatment, duration of immobilization and follow-up, final range of
      motion, and complications were recorded. Families were contacted to obtain long
      term Lysholm scores, return to activity, pain, and satisfaction with treatment.
      RESULTS: Seventy-six children (mean age, 12.4 y) met criteria with 29 ORIF, 28
      AAIF, and 19 CMC. Radiographic measurements between x-ray and computed tomography
      scans found a mean error of 1 mm (SD=1.33 mm; inter-class coefficient = 0.977, P
      < 0.001). Initial fracture displacement was similar between AAIF and ORIF, 10.3
      +/- 4.4 mm and 10.8 +/- 3.9 mm; but, less in CMC group (5.3 +/- 2.6 mm). The mean
      reduction amount was 8.6 +/- 4.7, 9.1 +/- 4.0, and 2.3 +/- 2.6 mm, respectively.
      A Bonferroni post hoc analysis revealed a difference between surgical and
      nonoperative reduction (P < 0.001), but not between AAIF and ORIF (P=0.9).
      Arthrofibrosis occurred with equal frequency in surgical cohorts (AAIF 12.5%,
      ORIF 11.1%), compared with none in the CMC group. Yet, the CMC group had a 16.7%
      risk for reoperation secondary to instability, loose bodies, or impingement.
      Twenty-four percent of each cohort was available (at mean 6.0 y) for interview
      with mean (median) Lysholm score: ORIF 97.4 (99), AAIF 95 (100), and CMC 86
      (97.5), P = 0.35. CONCLUSIONS: Open or arthroscopic treatment of displaced tibial
      spine fractures affords a better reduction than closed management, but with
      higher risk for arthrofibrosis. Closed management may be successful when
      displacement is < 5 mm, and advanced imaging may not be necessary to delineate
      the amount of displacement.

PMID- 25393568
TI  - Results of Surgical Management of Osteochondritis Dissecans of the Ankle in the
      Pediatric and Adolescent Population.
AB  - BACKGROUND: There is a paucity of published literature on operative management of
      osteochondritis dissecans (OCD) in the ankle in adolescents. This study seeks to
      elucidate patient and lesion characteristics associated with surgical success and
      failure as well as reporting functional outcomes. METHODS: Retrospective chart
      review identified all patients aged 18 years old or younger surgically treated
      for OCD of the ankle at our institution from 2001 to 2010. This included 109
      ankles in 100 patients (75 female, 25 male), mean age 14.3 +/- 2.3 years (range,
      7 to 18 y), with a median follow-up of 3.3 years (range, 1 to 10.8 y). Patient
      and lesion data, surgical procedure, clinical results, and complications were
      recorded. Postoperative radiographs were reviewed in 80 ankles. A return to sport
      survey and a Foot and Ankle Outcome Score (FAOS) was sent to all patients.
      Multivariate statistical analysis evaluated predictors of reoperation rate,
      Berndt and Harty clinical grade, and FAOS scores. Kaplan-Meier analysis was
      applied to determine freedom from reoperation. RESULTS: The OCD lesion was most
      commonly found on the medial talus (80, 73%). The most common procedures
      performed included transarticular drilling (59, 54%), fixation (22, 20%), and
      excision microfracture (27, 26%). The overall rate of reoperation was 27%
      (29/109). Berndt and Harty clinical grade was poor (33, 30%), fair (23, 21%), and
      good (53, 49%). Reoperation rates were significantly higher for OCD lesions in
      which postoperative radiographs had no change or looked worse (10/16, 63%) (P =
      0.002). Thirty-six of 44 survey respondents (82%) were satisfied and 37 (84%)
      returned to sports at a median time of 6 months. Average FAOS score was 77 +/-
      18. Multiple linear regression confirmed that female sex and elevated body mass
      index were significant negative predictors for FAOS score. CONCLUSIONS: The
      reoperation rate following surgical intervention for OCD of the ankle is high.
      Females and those with a higher body mass index may have worse subjective
      functional ankle outcomes.

PMID- 25393569
TI  - Can Radiographs Predict Outcome in Patients With Idiopathic Clubfeet Treated With
      the Ponseti Method?
AB  - BACKGROUND: The aim of this study was to determine if radiographic measurements,
      taken before tenotomy, can predict outcome in children with idiopathic clubfoot
      treated by the Ponseti method. METHODS: A retrospective chart and radiographic
      review was performed on children with idiopathic clubfoot treated with the
      Ponseti method over a 10-year period with minimum 2-year follow-up that had a
      forced dorsiflexion lateral foot radiograph before tenotomy. All angles were
      measured in duplicate on the pretenotomy radiographs, including: foot
      dorsiflexion (defined as the 90 minus the angle between the tibial shaft and a
      plastic plate used to dorsiflex the foot), tibio-calcaneal, talo-calcaneal, and
      talo-first metatarsal angles. Clinical review of patient records identified
      different patient outcomes: no additional treatment required, relapse (additional
      casting and/or surgery required), recurrence (any additional surgery required),
      or reconstruction (surgery not including repeat tenotomy). RESULTS: Forty-five
      patients (71 feet) were included in the study. The median age at follow-up was
      4.6 years. The intrareader reliability was acceptable for all measures. Thirteen
      of the 71 (18%) feet required additional surgery, occurring at a median age of
      3.6 years. Of the 4 radiographic measures, only pretenotomy foot dorsiflexion
      predicted recurrence (hazard ratio=0.96, P=0.03). Youden's method identified 16.6
      degrees of dorsiflexion as the optimal cutoff. Feet with at least that amount of
      dorsiflexion pretenotomy (n=21) experienced no recurrences; feet with less than
      that amount of dorsiflexion (n=50) experienced 13 recurrences (P=0.007).
      CONCLUSIONS: Reduced foot dorsiflexion on lateral forced dorsiflexion pretenotomy
      radiograph was associated with an increased risk of recurrence. Radiographic
      dorsiflexion to 15 degrees past neutral before tenotomy appears to predict
      successful treatment via the Ponseti method.

PMID- 25393570
TI  - The Inadequacy of Pediatric Fracture Care Information in Emergency Medicine and
      Pediatric Literature and Online Resources.
AB  - BACKGROUND: Emergency medicine and pediatric physicians often provide initial
      pediatric fracture care. Therefore, basic knowledge of the various treatment
      options is essential. The purpose of this study was to determine the accuracy of
      information commonly available to these physicians in textbooks and online
      regarding the management of pediatric supracondylar humerus and femoral shaft
      fractures. METHODS: The American Academy of Orthopaedic Surgeons Clinical
      Practice Guidelines for pediatric supracondylar humerus and femoral shaft
      fractures were used to assess the content of top selling emergency medicine and
      pediatric textbooks as well as the top returned Web sites after a Google search.
      Only guidelines that addressed initial patient management were included.
      Information provided in the texts was graded as consistent, inconsistent, or
      omitted. RESULTS: Five emergency medicine textbooks, 4 pediatric textbooks, and 5
      Web sites were assessed. Overall, these resources contained a mean 31.6%
      (SD=32.5) complete and correct information, whereas 3.6 % of the information was
      incorrect or inconsistent, and 64.8% was omitted. Emergency medicine textbooks
      had a mean of 34.3% (SD=28.3) correct and complete recommendations, 5.7%
      incorrect or incomplete recommendations, and 60% omissions. Pediatric textbooks
      were poor in addressing any of the American Academy of Orthopaedic Surgeons
      guidelines with an overall mean of 7.14% (SD=18.9) complete and correct
      recommendations, a single incorrect/incomplete recommendation, and 91.1%
      omissions. Online resources had a mean of 48.6% (SD=33.1) complete and correct
      recommendations, 5.72% incomplete or incorrect recommendations, and 45.7%
      omissions. CONCLUSIONS: This study highlights important deficiencies in resources
      available to pediatric and emergency medicine physicians seeking information on
      pediatric fracture management. Information in emergency medicine and pediatric
      textbooks as well as online is variable, with both inaccuracies and omissions
      being common. This lack of high-quality information could compromise patient
      care. Resources should be committed to ensuring accurate and complete information
      is readily available to all physicians providing pediatric fracture care. In
      addition, orthopaedic surgeons should take an active role to ensure that
      nonorthopaedic textbooks and online resources contain complete and accurate
      information.

PMID- 25393571
TI  - Long-term Outcomes of Triple Arthrodesis in Cerebral Palsy Patients.
AB  - BACKGROUND: Triple arthrodesis in the appropriately indicated cerebral palsy
      patient with a painful and/or rigid foot deformity can significantly alleviate
      pain and improve function. Limited data on long-term outcomes of triple
      arthrodesis in this patient population exist. In addition, there have been
      concerns about the long-term consequences of altered biomechanics in these
      patients on the tibiotalar (ankle) joint. METHODS: We retrospectively reviewed 21
      cerebral palsy patients who had undergone triple arthrodesis for a painful and/or
      rigid foot deformity at our institution with at least 10 years of clinical or
      radiographic follow-up. Preoperative, and the most recent, clinical evaluations
      and radiographs were reviewed. In addition, all 21 patients and/or caretakers
      responded to a questionnaire at the time of this study by means of telephone to
      assess subjective pain, analgesia use, walking aid necessity, walking distance,
      and satisfaction with the procedure. RESULTS: In this series of 21 cerebral palsy
      patients, 5 patients had bilateral surgery, resulting in 26 operative feet. The
      mean age at the time of surgery was 19.4 years and most recent clinical or
      radiographic follow-up was 22.1 years postoperatively. Preoperative foot
      deformity was characterized by hindfoot valgus in 66.7% (14/21) and varus in
      33.3% (7/21) of patients. Postoperatively, fusion was achieved in 96.2% (25/26)
      of feet. At final follow-up, 3 feet (11.5%) demonstrated tibiotalar joint
      arthritis, 1 (3.8%) had midfoot arthritis, and 10 (38.5%) had residual deformity.
      Of the total patients, 95.2% (20/21) were satisfied with the outcome and 61.9%
      (13/21) reported pain-free ambulation. There was no association between eventual
      functional outcome and preoperative diagnosis, preoperative foot deformity,
      postoperative tibiotalar joint arthritis, or postoperative residual deformity.
      CONCLUSIONS: Triple arthrodesis is a surgical option in cerebral palsy patients
      with painful and/or rigid foot deformities. From this series, successful outcomes
      can be expected as long as bony union is achieved. The incidence of tibiotalar
      arthritis is relatively low and not associated with long-term functional outcome.
      In addition, preoperative and residual postoperative foot deformity is not
      associated with long-term outcome.

PMID- 25393572
TI  - Osteosynthesis in situ for lateral condyle nonunion in children.
AB  - BACKGROUND: This study investigated the efficacy of osteosynthesis in situ by
      evaluating the functional and cosmetic results in children with nonunion of
      lateral condyle fractures. METHODS: Sixteen consecutive patients were treated
      with in situ fixation consisting of minimal curettage of fracture gap and screw
      compression of metaphyseal fragments without bone grafting. The mean age at the
      time of surgery was 5.6 years (range, 1 to 10 y). The mean interval between the
      initial lateral condylar fracture and surgery was 4.8 months (range, 3 to 12 mo).
      The average amount of displacement measured on radiographs was 6.6 mm medially
      and 7.4 mm laterally. Outcome was assessed by clinical and radiologic evaluation
      at the latest follow-up. RESULTS: All patients achieved bony union. The mean
      duration of follow-up was 45.4 months (range, 24 to 67 mo). The range of motion
      and flexion contracture improved postoperatively in all patients. There was no
      evidence of premature growth arrest, osteonecrosis, or fishtail deformity until
      last follow-up. The overall result was excellent in 5, good in 10, and fair in 1
      patient. However, 3 patients developed valgus or varus deformities of >10
      degrees. CONCLUSIONS: Osteosynthesis in situ can be an effective and safe
      treatment for achieving bone union and improved elbow motion and preventing
      avascular necrosis. However, valgus or varus deformities may occur after this
      procedure and corrective osteotomy may be necessary. LEVEL OF EVIDENCE: Level IV 
      case series.

PMID- 25393573
TI  - Surgical Treatment of Spinal Deformity in Patients With CLOVES Syndrome: A Report
      of 4 Cases.
AB  - BACKGROUND: CLOVES syndrome is a rare genetic condition manifested by lipomatous
      overgrowth of the trunk, vascular, and epidermal abnormalities, and skeletal
      anomalies including spinal deformity. The treatment of spinal deformity in these
      patients has not been described in the literature. METHODS: A retrospective
      review of the clinical and radiographic data on patient with CLOVES syndrome.
      RESULTS: Four patients were operated on at our institutions with CLOVES syndrome
      and resultant spinal deformity. One patient had postlaminoplasty cervical
      kyphosis and 3 patients had thoracic spinal deformities. All patients had
      paraspinal/intraspinal infiltration with high-flow vascular lesions and 3 of the
      patients had previous neurosurgical treatment for intraspinal disease. All
      patients obtained fusion with no neurological sequelae from deformity surgery.
      There was 1 complication, a patient had an intraoperative pulmonary embolus
      despite having an inferior caval filter requiring termination of surgery. The
      patient survived and underwent posterior fusion 4 months later, after recovery
      and placement of a superior caval filter. The unique characteristics of this
      disorder and resultant challenges encountered during care are described.
      CONCLUSIONS: CLOVES syndrome is a rare and challenging disorder with unique
      characteristics placing patients at risk for complications related to surgery for
      spinal deformity. Multidisciplinary approaches along with understanding of the
      potential pitfalls in treatment are paramount to successful treatment.

PMID- 25393574
TI  - Evaluation of Patient Satisfaction Surveys in Pediatric Orthopaedics.
AB  - BACKGROUND: Patient satisfaction survey scores are increasingly being tied to
      incentive compensation, impact how we practice medicine, influence decisions on
      where patients seek care, and in the future may be required for accreditation.
      The goal of this study is to compare the results of an internal distribution of
      patient satisfaction surveys at the point of care to responses received by mail
      in a hospital-based, high-volume pediatric orthopaedic practice. METHODS: A
      pediatric outpatient survey is used at our institution to evaluate patient
      satisfaction. Surveys are randomly mailed out to families seen in our clinic by
      the survey vendor, and the results are determined on a quarterly basis. We
      distributed the same survey in a similar manner in our clinic. The results of the
      surveys, external/mailed (EXM) versus internal/point of care (INP) over the same
      3-month time period (second quarter 2013) were compared. The survey questions are
      dichotomized from an ordinal scale into either excellent (9 to 10) or not
      excellent (0 to 8) commonly used in patient satisfaction methodology. We
      evaluated the raw data from the INP surveys for the question on provider rating
      by evaluating the mean score, the standard excellent response (9 to 10), and an
      expanded excellent response (8 to 10). RESULTS: Response rate was 72/469 (15.4%)
      for EXM, and 231/333 (69.4%) for INP. An excellent response for the "rating your
      provider" question was 72.2% (EXM) versus 84.8% (INP) (P=0.015). Our analysis of
      the raw data (INP) has a mean rating of 9.42. The expanded scale (8 to 10) for an
      excellent response increased the provider rating to 94.4% (P=0.001). Waiting time
      response within 15 minutes was the only item that correlated with rating of
      provider (P=0.02). For the majority of the items, the INP responses were
      consistently higher than the EXM responses, including 6/7 responses that were
      statistically significant (P<0.05). CONCLUSIONS: As mandated by the Centers for
      Medicare and Medicaid Services, patient satisfaction surveys will be important in
      determining health care outcomes. Properly designed and administered surveys
      provide robust measures of quality. Our study reinforces methodological concerns
      about patient satisfaction surveys distributed in a high-volume pediatric
      subspecialty practice. Further research is needed to evaluate the patients'
      health care experience and true quality of care in pediatric subspecialty
      ambulatory settings.

PMID- 25393575
TI  - The Relationship Between Accessory Navicular and Flat Foot: A Radiologic Study.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      accessory navicular (AN) and flat foot and to evaluate the association between
      flat foot and the symptoms of patients with AN. METHODS: We enrolled 196 patients
      with painful or asymptomatic AN in this study. Patients who were older than 18
      years or who had no weight-bearing radiographs of the feet were not included.
      Another 46 normal participants were used as a control group. The AN group was
      divided into 3 subgroups: a group with asymptomatic AN; a symptomatic group that
      had not undergone excision; and a symptomatic group that had undergone surgery.
      Seven radiographic indices were measured including calcaneal pitch angle,
      tibiocalcaneal angle, talocalcaneal angle, naviculocuboid overlap, talonavicular
      coverage angle, lateral talo-first metatarsal angle, and AP talo-first metatarsal
      angle. Groups were compared regarding age, sex, presence of pain at the time of
      surgery, and radiographic parameters. RESULTS: The calcaneal pitch angle in the
      AN group was significantly smaller than that of controls (P=0.004).
      Naviculocuboid overlap (P=0.001), talonavicular coverage angle (P<0.001), lateral
      talo-first metatarsal angle (P=0.014), and AP talo-first metatarsal angle
      (P<0.001) were significantly larger in the AN group than in controls. No
      significant radiologic differences were seen between patients with symptomatic
      and asymptomatic AN. No significant radiographic differences were found between
      the groups of patients who had and who had not had bone excised. CONCLUSIONS: AN
      associated with radiographic parameters felt to be representative of a flat foot;
      however, the degree of flat foot was not associated with the development and
      severity of symptoms in patients with AN.

PMID- 25393577
TI  - Epidemiology and treatment of lacrimal gland tumors: a population-based cohort
      analysis.
AB  - IMPORTANCE: Primary tumors of the lacrimal gland are rare and are associated with
      substantial morbidity and mortality. The literature regarding these tumors is
      limited to case series and case reports. OBJECTIVE: To examine the incidence,
      treatment, and overall survival (OS) and disease-specific survival (DSS) of
      patients with cancer of the lacrimal gland. DESIGN, SETTING, AND PARTICIPANTS:
      Population-based cohort analysis using the Surveillance, Epidemiology, and End
      Results (SEER) database to identify patients with primary tumors of the lacrimal
      gland from 1973 to 2010. MAIN OUTCOMES AND MEASURES: Overall survival and DSS.
      RESULTS: A total of 321 patients with nonlymphoid tumors of the lacrimal gland
      were identified. The most common histological subtypes were adenoid cystic
      carcinoma (ACC) (32.1%) and squamous cell carcinoma (SCC) (29.9%). Survival
      analysis revealed a 5-year OS and DSS for all lacrimal gland tumors of 60% and
      75%, respectively. On univariate analysis, low tumor grade (P = .04) and surgical
      treatment (P < .001) were associated with significantly better OS. For ACC
      tumors, surgery (P = .009), but not radiotherapy (P = .44), was found to
      significantly improve OS. For SCC tumors, surgical treatment significantly
      improved both OS (P < .001) and DSS (P = .004); radiation therapy also
      significantly improved OS (P = .03). Using a multivariable analysis model, age
      (hazard ratio [HR], 1.03 [95% CI, 1.01-1.04]; P < .001), surgery (HR, 0.43 [95%
      CI, 0.25-0.75]; P = .003), and T stage at presentation (HR, 1.18 [95% CI, 1.01
      1.37]; P = .03) were found to be independent predictors of OS. For ACC alone, age
      (HR, 1.04 [95% CI, 1.02-1.06]; P < .001) and surgery (HR, 0.35 [95% CI, 0.13
      0.91]; P = .03) were independent predictors of OS. For SCC, age (HR, 1.05 [95%
      CI, 1.02-1.09]; P = .005), surgical resection (HR, 0.31 [95% CI, 0.12-0.83]; P =
      .02), and radiation therapy (HR, 0.33 [95% CI, 0.14-0.80]; P = .01) were
      independent predictors of OS. CONCLUSIONS AND RELEVANCE: Our study demonstrates
      that ACC is the most common malignant epithelial neoplasm of the lacrimal gland.
      Determinants of survival for tumors of the lacrimal gland include age at
      diagnosis and surgical therapy. Radiation therapy is associated with improved DSS
      in SCC but not in ACC.

PMID- 25393578
TI  - Quantitative analysis of single amino acid variant peptides associated with
      pancreatic cancer in serum by an isobaric labeling quantitative method.
AB  - Single amino acid variations are highly associated with many human diseases. The
      direct detection of peptides containing single amino acid variants (SAAVs)
      derived from nonsynonymous single nucleotide polymorphisms (SNPs) in serum can
      provide unique opportunities for SAAV associated biomarker discovery. In the
      present study, an isobaric labeling quantitative strategy was applied to identify
      and quantify variant peptides in serum samples of pancreatic cancer patients and
      other benign controls. The largest number of SAAV peptides to date in serum
      including 96 unique variant peptides were quantified in this quantitative
      analysis, of which five variant peptides showed a statistically significant
      difference between pancreatic cancer and other controls (p-value < 0.05).
      Significant differences in the variant peptide SDNCEDTPEAGYFAVAVVK from
      serotransferrin were detected between pancreatic cancer and controls, which was
      further validated by selected reaction monitoring (SRM) analysis. The novel
      biomarker panel obtained by combining alpha-1-antichymotrypsin (AACT),
      Thrombospondin-1 (THBS1) and this variant peptide showed an excellent diagnostic
      performance in discriminating pancreatic cancer from healthy controls (AUC =
      0.98) and chronic pancreatitis (AUC = 0.90). These results suggest that large
      scale analysis of SAAV peptides in serum may provide a new direction for
      biomarker discovery research. 

PMID- 25393585
TI  - Effects of JNK1/2 on the inflammation cytokine TNF-alpha-enhanced production of
      MMP-3 in human dental pulp fibroblast-like cells.
AB  - AIM: To investigate the effects of the c-Jun N-terminal kinase (JNK1/2) on the
      inflammation cytokine tumour necrosis factor-alpha (TNF-alpha)-enhanced
      production of matrix metalloproteinase-3 (MMP-3) in human dental pulp fibroblast
      like cells (HPFs). METHODOLOGY: HPFs were grown from pulp explants from healthy
      donors. Primary cultures were established by culturing the cells for 20 to 30
      days. The experiments with HPFs were performed between passages 3 and 10. The
      HPFs were incubated in serum-free medium containing TNF-alpha for 24 h. The
      medium in each well was prepared in SDS sample buffer and was analysed for MMP-3
      by Western blotting. RESULTS: JNK inhibitor SP601245 markedly inhibited the
      production of MMP-3 in TNF-alpha-stimulated human dental pulp fibroblasts. MMP-3
      production was enhanced by TNF-alpha in HPFs; silencing JNK1 and JNK2 expression
      inhibited this activation. cAMP response element-binding protein (CREB) was
      activated by TNF-alpha in HPFs; silencing JNK1 and JNK2 expression inhibited this
      activation. CONCLUSION: The activation of CREB via JNK pathways in the presence
      of TNF-alpha occurred with enhancement of MMP-3 production in dental pulp
      fibroblasts.

PMID- 25393584
TI  - SpoIIID-mediated regulation of sigmaK function during Clostridium difficile
      sporulation.
AB  - The spore-forming bacterial pathogen Clostridium difficile is a leading cause of
      health-care-associated diarrhea worldwide. Although C. difficile spore formation
      is essential for disease transmission, the regulatory pathways that control this
      developmental process have only been partially characterized. In the well-studied
      spore-former Bacillus subtilis, the highly conserved sigma(E) , SpoIIID and
      sigma(K) regulatory proteins control gene expression in the mother cell to ensure
      proper spore formation. To define the precise requirement for SpoIIID and
      sigma(K) during C. difficile sporulation, we analyzed spoIIID and sigK mutants
      using heterologous expression systems and RNA-Seq transcriptional profiling.
      These analyses revealed that expression of sigK from a SpoIIID-independent
      promoter largely bypasses the need for SpoIIID to produce heat-resistant spores.
      We also observed that sigma(K) is active upon translation, suggesting that
      SpoIIID primarily functions to activate sigK. SpoIIID nevertheless plays
      auxiliary roles during sporulation, as it enhances levels of the exosporium
      morphogenetic protein CdeC in a sigma(K) -dependent manner. Analyses of purified
      spores further revealed that SpoIIID and sigma(K) control the adherence of the
      CotB coat protein to C. difficile spores, indicating that these proteins regulate
      multiple stages of spore formation. Collectively, these results highlight that
      diverse mechanisms control spore formation in the Firmicutes.

PMID- 25393586
TI  - Mutant KRAS and GNAS DNA Concentrations in Secretin-Stimulated Pancreatic Fluid
      Collected from the Pancreatic Duct and the Duodenal Lumen.
AB  - OBJECTIVES: The analysis of secretin-stimulated pancreatic fluid is being
      evaluated as an approach to improve the early detection of pancreatic cancer and
      pancreatic precursor neoplasms. The method of pancreatic fluid sampling may have
      a significant impact on tumor marker measurements. The aim of this study was to
      compare concentrations of mutant DNA in pancreatic fluid from patients who had
      samples collected from both the pancreatic duct and duodenal lumen. METHODS:
      Thirty-six participants enrolled in the Cancer of the Pancreas Screening studies
      at Johns Hopkins Hospital who had secretin-stimulated pancreatic fluid collected
      from the duodenum during endoscopic ultrasound (EUS) and from the pancreatic duct
      during subsequent endoscopic retrograde cholangiopancreatography. Mutant KRAS and
      GNAS DNA concentrations were measured in pancreatic fluid samples using digital
      high-resolution melt-curve analysis and pyrosequencing and were related total DNA
      concentrations in these samples. RESULTS: Thirty-four patients had subtle
      parenchymal abnormalities by EUS; seven had small pancreatic cysts; none had
      pancreatic cancer. KRAS mutations were detected in 29 of 36 (80.6%) pancreatic
      duct fluid samples. Of these 29 patients, 23 had mutations detected in their
      duodenal fluid (79.3%). Patients with detectable pancreatic fluid but not
      duodenal fluid KRAS mutations had lower average pancreatic duct fluid KRAS
      mutation concentrations (P=0.01). Patients with KRAS or GNAS mutations detected
      in pancreatic fluid but not duodenal fluid had higher total DNA concentrations in
      their duodenal compared with pancreatic fluid (P=0.03). KRAS and GNAS mutation
      concentrations were higher in pancreatic duct fluid samples than in matching
      duodenal fluid samples (for KRAS: 2.62 vs. 0.39%, P<0.0001). CONCLUSIONS: KRAS
      and GNAS mutation concentrations are significantly lower in secretin-stimulated
      pancreatic fluid samples collected from the duodenum compared with samples
      collected from the pancreatic duct. Efforts to improve the purity of pancreatic
      fluid collections from the duodenum could improve the detection of mutations
      arising from the pancreas.

PMID- 25393587
TI  - Magical thinking.

PMID- 25393588
TI  - Palladium-catalyzed sequential C-N/C-O bond formations: synthesis of oxazole
      derivatives from amides and ketones.
AB  - A highly efficient method for the synthesis of oxazole derivatives from simple
      amides and ketones has been established via a Pd(II)-catalyzed sp(2) C-H
      activation pathway in one step. The reaction is supposed to proceed through a C-N
      bond formation followed by a C-O bond formation closing the ring. Because of the
      simple and readily available starting materials, easy operation, and high
      bioactivity of oxazoles, this strategy can be broadly applied to medical
      chemistry. 

PMID- 25393589
TI  - Are caudal blocks for pain control safe in children? an analysis of 18,650 caudal
      blocks from the Pediatric Regional Anesthesia Network (PRAN) database.
AB  - BACKGROUND: The caudal block is the most commonly performed regional anesthesia
      technique in pediatric patients undergoing surgical procedures, but safety
      concerns raised by previous reports remain to be addressed. Our main objective in
      current investigation was to estimate the overall and specific incidence of
      complications associated with the performance of caudal block in children.
      METHODS: This was an observational study using the Pediatric Regional Anesthesia
      Network database. A complication after a caudal block was defined by the presence
      of at least 1 of the following: block failure, vascular puncture, intravascular
      test dose, dural puncture, seizure, cardiac arrest, sacral pain, or neurologic
      symptoms. In addition, if a complication was also coded, the presence of
      temporary or permanent sequelae was evaluated. Additional exploratory analyses
      were performed to identify patterns of local anesthetic dosage. RESULTS: Eighteen
      thousand six hundred-fifty children who received a caudal block were included in
      the study. The overall estimated incidence (95% confidence interval [CI]) of
      complications after caudal blocks was 1.9% (1.7%-2.1%). Patients who developed
      complications were younger, median (interquartile range) of 11 (5-24) months,
      compared to those who did not develop any complications, 14 (7-29) months, P =
      0.001. The most common complications were block failure, blood aspiration, and
      intravascular injection. No cases of temporary or permanent sequelae were
      identified leading to an estimated incidence (95% CI) of 0.005% (- % to 0.03%).
      Four thousand four hundred-six of 17,867 (24.6%; 95% CI, 24%-25.2%) subjects
      received doses (>2 mg of bupivacaine equivalents/kg) that could be potentially
      unsafe. CONCLUSIONS: Safety concerns should not be a barrier to the use of caudal
      blocks in children assuming an appropriate selection of local anesthetic dosage.

PMID- 25393590
TI  - Blood/Gas partition coefficients for isoflurane, sevoflurane, and desflurane in a
      clinically relevant patient population.
AB  - BACKGROUND: The blood/gas partition coefficient of a certain volatile anesthetic
      is of clinical importance because it determines its velocity of uptake into and
      elimination from the body of a patient and thus its pharmacokinetic behavior. To
      date, the blood/gas partition coefficients of isoflurane, sevoflurane, and
      desflurane have been measured in small numbers of subjects or in particular study
      groups, for example, healthy volunteers, patients experiencing a common kind of
      disease, or mothers immediately after giving birth. The objective of this study
      was to determine the blood/gas partition coefficients of these volatile
      anesthetics at 37 degrees C in a larger clinically relevant and adult patient
      population. Furthermore, we tested whether age, gender, body mass index,
      hemoglobin concentration, or hematocrit had an influence on the coefficients.
      METHODS: Blood samples were taken from 120 fasting operative patients with ASA
      physical status I to III and aged 19 to 86 years. All subjects were randomly
      enrolled in study groups for the separate determinations of the blood/gas
      partition coefficients of isoflurane (n = 41), sevoflurane (n = 41), and
      desflurane (n = 38) by headspace gas chromatography. To check the quality of the
      measurements, we determined the distilled water/gas partition coefficients of
      those anesthetics and compared them with previously published values. RESULTS: We
      found a blood/gas partition coefficient of 1.45 +/- 0.12 (mean +/- SD) for
      isoflurane, 0.74 +/- 0.06 for sevoflurane, and 0.57 +/- 0.04 for desflurane.
      Values of this study are 5.07%, 12.12%, and 7.55% higher for isoflurane,
      sevoflurane, and desflurane, respectively, than the previously published mean
      values (all P <= 0.001). There were only trends for small correlations between
      the blood/gas partition coefficient of isoflurane and hemoglobin concentration
      (Pearson r = 0.32; P = 0.041) and hematocrit (r = 0.37; P = 0.016). We found no
      other potentially significant correlations of the partition coefficients with
      patient age, body mass index, hemoglobin concentration, or hematocrit (all
      remaining P > 0.069). Furthermore, the coefficients did not differ significantly
      between female and male patients. The evaluation of the distilled water/gas
      partition coefficients of isoflurane (0.59 +/- 0.04), sevoflurane (0.37 +/-
      0.04), and desflurane (0.27 +/- 0.03) proved the validity of the gas
      chromatography method used in this study. CONCLUSIONS: The blood/gas partition
      coefficients of the modern volatile anesthetics, in particular, those of
      sevoflurane and desflurane, may be higher than that has been hitherto reported.
      Therefore, their uptake and elimination may occur more slowly in some patients
      than has been supposed. The blood/gas partition coefficients of isoflurane,
      sevoflurane, and desflurane measured in this study appear to be representative
      because they were determined in a clinically and numerically relevant patient
      cohort.

PMID- 25393591
TI  - Visualization of fibrinogen alphaC regions and their arrangement during fibrin
      network formation by high-resolution AFM.
AB  - BACKGROUND: Fibrinogen has been intensively studied with transmission electron
      microscopy and x-ray diffraction. But until now, a complete 3D structure of the
      molecule has not yet been available because the two highly flexible alphaC
      regions could not be resolved in fibrinogen crystals. This study was aimed at
      determining whether the alphaC regions can be visualized by high-resolution
      atomic force microscopy. METHODS: Atomic force microscopy with super high
      resolution was used to image single molecules of fibrinogen and fibrin
      associates. The key approach was to use a graphite surface modified with the
      monolayer of amphiphilic carbohydrate-glycine molecules and unique supersharp
      cantilevers with 1 nm tip diameter. RESULTS: Fibrinogen alphaC regions were
      visualized along with the complete domain structure of the protein. In almost all
      molecules at pH 7.4 the D domain regions had one or two protrusions of average
      height 0.4 +/- 0.1 nm and length 21 +/- 6 nm. The complex, formed between
      thrombin and fibrinogen, was also visualized. Images of growing fibrin fibers
      with clearly visible alphaC regions have been obtained. CONCLUSIONS: Fibrin
      alphaC regions were visible in protofibrils and large fibers; alphaC regions
      intertwined near a branchpoint and looked like a zipper. These results support
      the idea that alphaC regions are involved in the thickening of fibrin fibers. In
      addition, new details were revealed about the behavior of individual fibrin
      molecules during formation of the fibrin network. Under the diluted condition,
      the positioning of the alphaC regions could suggest their involvement in long
      range interactions between fibrin but not fibrinogen molecules.

PMID- 25393592
TI  - DSM-IV and DSM-5 alcohol use disorder among young Swiss men.
AB  - BACKGROUND AND AIMS: Previous studies suggest that the new DSM-5 criteria for
      alcohol use disorder (AUD) will increase the apparent prevalence of AUD. This
      study estimates the 12-month prevalence of AUD using both DSM-IV and DSM-5
      criteria and compares the characteristics of men in a high risk sample who meet
      both, only one and neither sets of diagnostic criteria. DESIGN, SETTING AND
      PARTICIPANTS: 5943 Swiss men aged 18-25 years who participated in the Cohort
      Study on Substance Use Risk Factors (C-SURF), a population-based cohort study
      recruited from three of the six military recruitment centres in Switzerland
      (response rate = 79.2%). MEASUREMENTS: DSM-IV and DSM-5 criteria, alcohol use
      patterns, and other substance use were assessed. FINDINGS: Approximately 31.7%
      (30.5-32.8) of individuals met DSM-5 AUD criteria [21.2% mild (20.1-22.2); 10.5%
      moderate/severe (9.7-11.3)], which was less than the total rate when DSM-IV
      criteria for alcohol abuse (AA) and alcohol dependence (AD) were combined [36.8%
      overall (35.5-37.9); 26.6% AA (25.4-27.7); 10.2% AD (9.4-10.9)]. Of 2479
      respondents meeting criteria for either diagnoses, 1585 (63.9%) met criteria for
      both. For those meeting DSM-IV criteria only (n = 598, 24.1%), hazardous use was
      most prevalent, whereas the criteria larger/longer use than intended and
      tolerance to alcohol were most prevalent for respondents meeting DSM-5 criteria
      only (n = 296, 11.9%). Two in five DSM-IV alcohol abuse cases and one-third of
      DSM-5 mild AUD individuals fulfilled the diagnostic criteria due to the hazardous
      use criterion. The addition of the craving and excluding of legal criterion,
      respectively, did not affect estimated AUD prevalence. CONCLUSIONS: In a high
      risk sample of young Swiss males, prevalence of alcohol use disorder as diagnosed
      by DSM-5 was slightly lower than prevalence of DSM-IV diagnosis of dependence
      plus abuse; 63.9% of those who met either criterion met criteria for both.

PMID- 25393593
TI  - Comparison of survival at adult versus pediatric treatment centers for rare
      pediatric tumors in an adolescent and young adult (AYA) population in the State
      of Georgia.
AB  - BACKGROUND: The type of treatment center where 15-21-year-old adolescent and
      young adult (AYA) patients with rare pediatric tumors achieve their best clinical
      outcome is unknown. PROCEDURE: We performed a retrospective analysis using the
      Georgia Cancer Registry (GCR) of 15-21-year old patients with a malignant, rare
      pediatric tumor diagnosed during the period from 2000-2009. Patients were
      identified as being treated at one of five Georgia pediatric cancer centers or at
      an adult center. Data were analyzed for 10 year overall survival, patient
      characteristics associated with death, and patient characteristics present at
      diagnosis associated with choice of treatment center. RESULTS: There was a total
      of 479 patients in our final study population, of which 379 (79.1%) were treated
      at an adult center and 100 (20.9%) were treated at a pediatric center. Patients
      treated at an adult center had a 10 year overall survival of 86% compared to 85%
      for patients treated at a pediatric center (P = 0.31). Race and poverty were not
      significantly associated with death. Patients with nasopharyngeal carcinoma (OR =
      7.38; 95% CI = 2.30-23.75) and 'other carcinomas' (OR = 2.64; 95% CI = 1.25-5.60)
      were more likely to be treated at a pediatric center. Patients with higher-stage
      disease (OR = 4.24; 95% CI = 1.71-10.52) and higher poverty (OR = 2.32; 95% CI =
      1.23-4.37) were also more likely to be treated at a pediatric center. CONCLUSION:
      Our data suggest that there is no difference in survival for 15-21-year old
      patients with rare pediatric tumors when treated at an adult or pediatric center.

PMID- 25393594
TI  - Unfamiliar face matching: Pairs out-perform individuals and provide a route to
      training.
AB  - Matching unfamiliar faces is known to be difficult. Here, we ask whether
      performance can be improved by asking viewers to work in pairs, a manipulation
      known to increase accuracy for low-level visual discrimination tasks. Across four
      experiments we consistently find that face matching accuracy is higher for pairs
      of viewers than for individuals. This 'pairs advantage' is generally driven by
      adopting the response of the higher scoring partner. However, when the task
      becomes difficult, both partners' performance is improved by working in a pair.
      In two experiments, we find evidence that working in a pair can lead to
      subsequent improvements in individual performance, specifically for viewers whose
      accuracy is initially low. The pairs' technique therefore offers the opportunity
      for substantial improvements in face matching performance, along with an added
      training benefit. 

PMID- 25393595
TI  - Marked improvement in photoinduced cell death by a new tris-heteroleptic complex
      with dual action: singlet oxygen sensitization and ligand dissociation.
AB  - The new tris-heteroleptic complex [Ru(bpy)(dppn)(CH3CN)2](2+) (3, bpy = 2,2'
      bipyridine, dppn = benzo[i]dipyrido[3,2-a;2',3'-c]phenazine) was synthesized and
      characterized in an effort to generate a molecule capable of both singlet oxygen
      ((1)O2) production and ligand exchange upon irradiation. Such dual reactivity has
      the potential to be useful for increasing the efficacy of photochemotherapy drugs
      by acting via two different mechanisms simultaneously. The photochemical
      properties and photoinduced cytotoxicity of 3 were compared to those of
      [Ru(bpy)2(dppn)](2+) (1) and [Ru(bpy)2(CH3CN)2](2+) (2), since 1 sensitizes the
      production of (1)O2 and 2 undergoes ligand exchange of the monodentate CH3CN
      ligands with solvent when irradiated. The quantum yield of (1)O2 production was
      measured to be 0.72(2) for 3 in methanol, which is slightly lower than that of 1,
      Phi = 0.88(2), in the same solvent (lambdairr = 460 nm). Complex 3 also undergoes
      photoinduced ligand exchange when irradiated in H2O (lambdairr = 400 nm), but
      with a low quantum efficiency (<1%). These results are explained by the presence
      of the low-lying ligand-centered (3)pipi* excited state of 3 localized on the
      dppn ligand, thus decreasing the relative population of the higher energy (3)dd
      state; the latter is associated with ligand dissociation. Cytotoxicity data with
      HeLa cells reveal that complex 3 exhibits a greater photocytotoxicity index,
      1110, than does either 1 and 2, indicating that the dual-action complex is more
      photoactive toward cells in spite of its low ligand exchange quantum yield. 

PMID- 25393596
TI  - Flexible Organic Electronics in Biology: Materials and Devices.
AB  - At the convergence of organic electronics and biology, organic bioelectronics
      attracts great scientific interest. The potential applications of organic
      semiconductors to reversibly transmit biological signals or stimulate biological
      tissues inspires many research groups to explore the use of organic electronics
      in biological systems. Considering the surfaces of movable living tissues being
      arbitrarily curved at physiological environments, the flexibility of organic
      bioelectronic devices is of paramount importance in enabling stable and reliable
      performances by improving the contact and interaction of the devices with
      biological systems. Significant advances in flexible organic bio-electronics have
      been achieved in the areas of flexible organic thin film transistors (OTFTs),
      polymer electrodes, smart textiles, organic electrochemical ion pumps (OEIPs),
      ion bipolar junction transistors (IBJTs) and chemiresistors. This review will
      firstly discuss the materials used in flexible organic bioelectronics, which is
      followed by an overview on various types of flexible organic bioelectronic
      devices. The versatility of flexible organic bioelectronics promises a bright
      future for this emerging area. 

PMID- 25393597
TI  - Femtosecond laser spectroscopy of the rhodopsin photochromic reaction: a concept
      for ultrafast optical molecular switch creation (ultrafast reversible
      photoreaction of rhodopsin).
AB  - Ultrafast reverse photoreaction of visual pigment rhodopsin in the femtosecond
      time range at room temperature is demonstrated. Femtosecond two-pump probe
      experiments with a time resolution of 25 fs have been performed. The first rump
      pulse at 500 nm initiated cis-trans photoisomerization of rhodopsin chromophore,
      11-cis retinal, which resulted in the formation of the primary ground-state
      photoproduct within a mere 200 fs. The second pump pulse at 620 nm with a varying
      delay of 200 to 3750 fs relative to the first rump pulse, initiated the reverse
      phototransition of the primary photoproduct to rhodopsin. The results of this
      photoconversion have been observed on the differential spectra obtained after the
      action of two pump pulses at a time delay of 100 ps. It was found that optical
      density decreased at 560 nm in the spectral region of bathorhodopsin absorption
      and increased at 480 nm, where rhodopsin absorbs. Rhodopsin photoswitching
      efficiency shows oscillations as a function of the time delay between two rump
      pulses. The quantum yield of reverse photoreaction initiated by the second pump
      pulse falls within the range 15%+/-1%. The molecular mechanism of the ultrafast
      reversible photoreaction of visual pigment rhodopsin may be used as a concept for
      the development of an ultrafast optical molecular switch.

PMID- 25393598
TI  - Chitin and chitosan nanofibers: preparation and chemical modifications.
AB  - Chitin nanofibers are prepared from the exoskeletons of crabs and prawns, squid
      pens and mushrooms by a simple mechanical treatment after a series of
      purification steps. The nanofibers have fine nanofiber networks with a uniform
      width of approximately 10 nm. The method used for chitin-nanofiber isolation is
      also successfully applied to the cell walls of mushrooms. Commercial chitin and
      chitosan powders are also easily converted into nanofibers by mechanical
      treatment, since these powders consist of nanofiber aggregates. Grinders and high
      pressure waterjet systems are effective for disintegrating chitin into
      nanofibers. Acidic conditions are the key factor to facilitate mechanical
      fibrillation. Surface modification is an effective way to change the surface
      property and to endow nanofiber surface with other properties. Several
      modifications to the chitin NF surface are achieved, including acetylation,
      deacetylation, phthaloylation, naphthaloylation, maleylation, chlorination, TEMPO
      mediated oxidation, and graft polymerization. Those derivatives and their
      properties are characterized. 

PMID- 25393600
TI  - Propagation of electrical activity in uterine muscle during pregnancy: a review.
AB  - The uterine muscle (the myometrium) plays its most evident role during pregnancy,
      when quiescence is required for adequate nourishment and development of the
      foetus, and during labour, when forceful contractions are needed to expel the
      foetus and the other products of conception. The myometrium is composed of smooth
      muscle cells. Contraction is initiated by the spontaneous generation of
      electrical activity at the cell level in the form of action potentials. The
      mechanisms underlying uterine quiescence during pregnancy and electrical
      activation during labour remain largely unknown; as a consequence, the clinical
      management of preterm contractions during pregnancy and inefficient uterine
      contractility during labour remains suboptimal. In an effort to improve clinical
      management of uterine contractions, research has focused on understanding the
      propagation properties of the electrical activity of the uterus. Different
      perspectives have been undertaken, from animal and in vitro experiments up to
      clinical studies and dedicated methods for non-invasive parameter estimation. A
      comparison of the results is not straightforward due to the wide range of
      different approaches reported in the literature. However, previous studies
      unanimously reveal a unique complexity as compared to other organs in the pattern
      of uterine electrical activity propagation, which necessarily needs to be taken
      into consideration for future studies to be conclusive. The aim of this review is
      to structure current variegated knowledge on the properties of the uterus in
      terms of pacemaker position, pattern, direction and speed of the electrical
      activity during pregnancy and labour. 

PMID- 25393599
TI  - Valuation of depression co-occurring with a somatic condition: feasibility of the
      time trade-off task.
AB  - BACKGROUND: Health state valuations obtained from the general population are used
      for cost-utility analyses of health-care interventions. Currently, most studies
      have focused on valuations of somatic conditions, to a much lesser extent of
      mental states, that is, depression and even less on valuations of depression co
      occurring with somatic conditions. OBJECTIVE: We tested the feasibility of the
      time trade-off (TTO) task to elicit valuations for depression solitary or co
      occurring with a somatic condition. Moreover, we explored person- and state
      related factors that may affect valuations. DESIGN: During semi-structured
      interviews, 10 individuals (five women, mean age: 36 years) used a TTO task to
      value vignettes describing mild and severe depression; and mild depression co
      occurring with moderate and severe states of cancer, diabetes or heart disease.
      During valuations, participants were thinking aloud. Feasibility criteria were
      successful completion and difficulty/concentration (1-10); logical consistency of
      values; and comprehension of the TTO, based on qualitative analysis of think
      aloud data. Factors influencing valuations were generated from think aloud data.
      RESULTS: Participants reported satisfactory levels of difficulty (mean: 1.9) and
      concentration (mean: 8.3) and assigned consistent values. Qualitative analysis
      revealed difficulties with imagining: living with depression for lifetime (n =
      4); reaching the age of 80 (n = 6); and living with a somatic condition and
      mentally healthy (n = 6). Person- and state-related factors, for example
      perceived susceptibility to depression (n = 4), appeared to affect valuations.
      CONCLUSION: Quantitative findings supported feasibility of the valuation
      protocol, yet qualitative findings indicated that certain task aspects should be
      readdressed. Factors influencing valuations can be explored to better understand
      valuations.

PMID- 25393601
TI  - Adolescents' Physical Activity and Sedentary Behavior: A Pathway in Reducing
      Overweight and Obesity. The PRALIMAP 2-Year Cluster Randomized Controlled Trial.
AB  - BACKGROUND: explaining why and how overweight prevention programs were effective
      was a real need; especially the potential role of physical activity (PA) and
      sedentary behavior (SB) should be highlighted. This study aimed to evaluate the 2
      year effectiveness of a screening and care strategy in adolescents' weight
      reduction with regards to PA and SB change. METHODS: 1745 adolescents aged 15.1
      years from PRALIMAP trial was included (n = 840 for screening and care group and
      n = 905 for control group). PA and SB time (international physical activity
      questionnaire: IPAQ), body mass index (BMI), and BMI z-score were assessed at
      inclusion and after 2-year intervention. Hierarchical mixed models were applied.
      RESULTS: Compared with the control group, screening and care strategy was
      associated with an increase in global PA (58 min/week), a moderate PA (43
      min/week), the adherence to the French PA guidelines (OR = 1.3), and a decrease
      in SB (-198 min/week). The 2-year weight change decreased when adjusted for PA
      and SB suggesting that the effect of screening and care strategy was partly
      mediated by PA and SB. CONCLUSION: Screening and care intervention seemed to be
      effective in increasing PA and decreasing SB. The induced PA and SB modifications
      contributed to the observed weight change.

PMID- 25393602
TI  - Ultrasonographic biomicroscopy in lens-induced glaucoma.

PMID- 25393604
TI  - Integrating pharmacy services in primary care.

PMID- 25393603
TI  - Exploring the role of quantitative feedback in inhaler technique education: a
      cluster-randomised, two-arm, parallel-group, repeated-measures study.
AB  - BACKGROUND: Feedback is a critical component of any educational intervention.
      When it comes to feedback associated with inhaler technique education, there is a
      lack of knowledge on its role or its potential to solve the major issue of poor
      inhaler technique. AIMS: This study aims to explore the role of feedback in
      inhaler technique education and its impact on the inhaler technique of patients
      over time. METHODS: A parallel-group, repeated-measures study was conducted in
      the community pharmacy in which the effectiveness of current best practice
      inhaler technique education utilising qualitative visual feedback (Group 1) was
      compared with a combination of qualitative and quantitative visual feedback
      (Group 2). The impact of these two interventions on inhaler technique maintenance
      was evaluated. Community pharmacists were randomly allocated to recruit people
      with asthma who were using a dry powder inhaler. At Visit 1 their inhaler
      technique was evaluated and education delivered and they were followed up at
      Visit 2 (1 month later). RESULTS: Both educational interventions resulted in an
      increase in the proportion of patients with correct inhaler technique: from 4% to
      51% in Group 1 and from 6% to 83% in Group 2 (Pearson's Chi-Squared, P=0.03,
      n=49, and Pearson's Chi-Squared, P=0.01, n=48, respectively). The magnitude of
      improvement was statistically significantly higher for Group 2 compared with
      Group 1 (n=97, P=0.02, Pearson's Chi-Square test). CONCLUSIONS: The nature of
      feedback has an impact on the effectiveness of inhaler technique education with
      regard to correct inhaler technique maintenance over time.

PMID- 25393605
TI  - Use of Candida-specific chicken egg yolk antibodies to inhibit the adhering of
      Candida to denture base materials: prevention of denture stomatitis.
AB  - OBJECTIVES: Polyclonal anti-Candida chicken egg yolk antibodies (anti-IgY) were
      used to investigate the prevention of adherence of Candida species to denture
      base material in vitro. BACKGROUND: Candida is a potential virulence factor that
      can cause systemic infection and even death in immunocompromised individuals.
      Because long-term antifungal treatment may lead to the emergence of drug
      resistant strains, it is necessary to develop novel preventive measures and
      treatments for candidiasis. MATERIALS AND METHODS: Three types of chicken egg
      yolk antibodies were used in this study: non-specific antibody (control IgY),
      Candida albicans-specific antibody (anti-C.a.IgY) and Candida glabrata-specific
      antibody (anti-C.g.IgY). A mixture of different dilutions of each antibody with a
      suspension of Candida species and denture base material was incubated for 3 h,
      and then the colony-forming units of Candida on the denture base material were
      counted. RESULTS: Compared with control IgY, anti-C.a.IgY and anti-C.g.IgY
      significantly inhibited the adherence of C. albicans, but anti-C.a.IgY tended to
      be more potent than anti-C.g.IgY. The adherence of C. glabrata was also inhibited
      significantly by anti-C.a.IgY and anti-C.g.IgY with almost equivalent potency,
      indicating that their actions against C. glabrata were comparable. CONCLUSIONS:
      This study revealed the inhibitory effects of anti-C.a.IgY and anti-C.g.IgY
      against the adherence of C. albicans and C. glabrata to denture base material.
      This finding indicates the possibility of a beneficial effect of IgYs for the
      prevention of denture stomatitis and candidiasis in clinical settings.

PMID- 25393606
TI  - Political priority of oral health in Italy: an analysis of reasons for national
      neglect.
AB  - PURPOSE: Oral health remains a neglected area and its political priority on most
      national agendas is low. This analysis aimed to identify the political priority
      of oral health in Italy. BACKGROUND: Italian public health services are
      decentralised at the regional level and are financed by both central and local
      authorities. Despite certain legally guaranteed public oral health services,
      access to oral health care seems to be inhomogeneous. METHODS: Appraisal of the
      political priority of oral health in Italy uses the Political Power Framework as
      proposed by Shiffman and Smith. RESULTS AND DISCUSSION: There is no clear mandate
      for leadership or coordination within the oral health sector, resulting in
      fragmentation and in dominance of the private sector. As a consequence, oral
      diseases are mainly addressed through a curative rather than a preventive public
      health approach. Current, systematic and representative data are lacking.
      Therefore, the real burden of oral diseases is unknown and thus cannot be
      addressed adequately. Evidence-based, cost-effective and sustainable population
      wide public dental health interventions are not implemented on a large scale, and
      growing inequities in terms of access to care are not seen as a concern.
      CONCLUSION: Lack of relevant policies with a public health focus, absence of
      systematic oral health surveillance and limited access to care for large
      population groups are strong indicators that oral health is not a political
      priority. However, opportunities in the wider political environment could be used
      to facilitate analysis, discussion and change in order to improve political
      priority of oral health in Italy.

PMID- 25393607
TI  - Intracellular detection of ATP using an aptamer beacon covalently linked to
      graphene oxide resisting nonspecific probe displacement.
AB  - Fluorescent aptamer probes physisorbed on graphene oxide (GO) have recently
      emerged as a useful sensing platform. A signal is generated by analyte-induced
      probe desorption. To address nonspecific probe displacement and the false
      positive signal, we herein report a covalently linked aptamer probe for adenosine
      triphosphate (ATP) detection. A fluorophore and amino dual modified aptamer was
      linked to the carboxyl group on GO with a coupling efficiency of ~50%. The
      linearity, specificity, stability, and regeneration of the covalent sensor were
      systematically studied and compared to the physisorbed probe. Both sensors have
      similar sensitivity, but the covalent one is more resistant to nonspecific probe
      displacement by proteins. The covalent sensor has a dynamic range from 0.125 to 2
      mM ATP in buffer at room temperature and is resistance to DNase I. Intracellular
      ATP imaging was demonstrated using the covalent sensor, which generated a higher
      fluorescence signal than the physisorbed sensor. After the cells were stimulated
      with 5 mM Ca(2+) for ATP production, the intracellular signal enhanced by 31.8%.
      This work highlights the advantages of covalent aptamer sensors using GO as both
      a quencher and a delivery vehicle for intracellular metabolite detection. 

PMID- 25393608
TI  - Quality evaluation of sake treated with a two-stage system of low pressure carbon
      dioxide microbubbles.
AB  - To determine optimal temperature of a two-stage system of low pressure carbon
      dioxide microbubbles (MB-CO2) for inactivating enzymes in unpasteurized sake
      (UPS), the effect of two-stage MB-CO2 containing a heating coil at various
      temperatures on the inactivation of the alpha-glucosidase in UPS was
      investigated, and the quality of the sake treated by two-stage MB-CO2 was
      estimated by sensory evaluation and component analysis. alpha-Glucosidase
      activity in the UPS was completely inactivated by two-stage MB-CO2 with a heating
      coil at 45  degrees C for 50 min, 55  degrees C for 5 min, 65  degrees C for 10 s
      (MB65), and 75  degrees C for 1 s, respectively. The quality of the MB65's sake
      was determined to be significantly excellent by the sensory evaluation. The
      reason was suggested to be due to relatively low contents of free amino acids,
      change in organic acid balance, and less damage to volatile compounds. 

PMID- 25393610
TI  - Iridium-catalyzed synthesis of diaryl ethers by means of chemoselective C-F bond
      activation and the formation of B-F bonds.
AB  - Transition-metal-catalyzed C?F activation, in comparison with C?H activation, is
      more difficult to achieve and therefore less fully understood, mainly because
      carbon-fluorine bonds are the strongest known single bonds to carbon and have
      been very difficult to cleave. Transition-metal complexes are often more
      effective at cleaving stronger bonds, such as C(sp(2) )?X versus C(sp(3) )?X.
      Here, the iridium-catalyzed C?F activation of fluorarenes was achieved through
      the use of bis(pinacolato)diboron with the formation of the B?F bond and self
      coupling. This strategy provides a convenient method with which to convert
      fluoride aromatic compounds into symmetrical diaryl ether compounds. Moreover,
      the chemoselective products of the C?F bond cleavage were obtained at high yields
      with the C?Br and C?Cl bonds remaining. 

PMID- 25393609
TI  - Pre-synaptic C-terminal truncated tau is released from cortical synapses in
      Alzheimer's disease.
AB  - The microtubule-associated protein tau has primarily been associated with axonal
      location and function; however, recent work shows tau release from neurons and
      suggests an important role for tau in synaptic plasticity. In our study, we
      measured synaptic levels of total tau using synaptosomes prepared from
      cryopreserved human postmortem Alzheimer's disease (AD) and control samples. Flow
      cytometry data show that a majority of synaptic terminals are highly
      immunolabeled with the total tau antibody (HT7) in both AD and control samples.
      Immunoblots of synaptosomal fractions reveal increases in a 20 kDa tau fragment
      and in tau dimers in AD synapses, and terminal-specific antibodies show that in
      many synaptosome samples tau lacks a C-terminus. Flow cytometry experiments to
      quantify the extent of C-terminal truncation reveal that only 15-25% of
      synaptosomes are positive for intact C-terminal tau. Potassium-induced
      depolarization demonstrates release of tau and tau fragments from pre-synaptic
      terminals, with increased release from AD compared to control samples. This study
      indicates that tau is normally highly localized to synaptic terminals in cortex
      where it is well-positioned to affect synaptic plasticity. Tau cleavage may
      facilitate tau aggregation as well as tau secretion and propagation of tau
      pathology from the pre-synaptic compartment in AD. Results demonstrate the
      abundance of tau, mainly C-terminal truncated tau, in synaptic terminals in aged
      control and in Alzheimer's disease (AD) samples. Tau fragments and
      dimers/oligomers are prominent in AD synapses. Following depolarization, tau
      release is potentiated in AD nerve terminals compared to aged controls. We
      hypothesize (i) endosomal release of the different tau peptides from AD synapses,
      and (ii) together with phosphorylation, fragmentation of synaptic tau exacerbates
      tau aggregation, synaptic dysfunction, and the spread of tau pathology in AD.
      Abeta = amyloid-beta.

PMID- 25393611
TI  - Exploring the free energy and conformational landscape of tRNA at high
      temperature and pressure.
AB  - A combined temperature- and pressure-dependent study was employed to reveal the
      conformational and free-energy landscape of phenylalanine transfer RNA (tRNA(Phe)
      ), a known model for RNA function, to elucidate the features that are essential
      in determining its stability. These studies also help explore its structural
      properties under extreme environmental conditions, such as low/high temperatures
      and high pressures. To this end, fluorescence and FTIR spectroscopies,
      calorimetric and small-angle scattering measurements were carried out at
      different ion concentrations over a wide range of temperatures and pressures up
      to several hundred MPa. Compared with the pronounced temperature effect, the
      pressure-dependent structural changes of tRNA(Phe) are small. A maximum of only
      15 % unpaired bases is observed upon pressurization up to 1 GPa. RNA unfolding
      differs not only from protein unfolding, but also from DNA melting. Its pressure
      stability seems to be similar to that of noncanonical DNA structures. 

PMID- 25393612
TI  - Structure of framework aluminum Lewis sites and perturbed aluminum atoms in
      zeolites as determined by 27Al{1H} REDOR (3Q) MAS NMR spectroscopy and
      DFT/molecular mechanics.
AB  - Zeolites are highly important heterogeneous catalysts. Besides Bronsted SiOHAl
      acid sites, also framework AlFR Lewis acid sites are often found in their H
      forms. The formation of AlFR Lewis sites in zeolites is a key issue regarding
      their selectivity in acid-catalyzed reactions. The local structures of AlFR Lewis
      sites in dehydrated zeolites and their precursors--"perturbed" AlFR atoms in
      hydrated zeolites--were studied by high-resolution MAS NMR and FTIR spectroscopy
      and DFT/MM calculations. Perturbed framework Al atoms correspond to (SiO)3AlOH
      groups and are characterized by a broad (27)Al NMR resonance (deltai = 59-62 ppm,
      CQ = 5 MHz, and eta = 0.3-0.4) with a shoulder at 40 ppm in the (27)Al MAS NMR
      spectrum. Dehydroxylation of (SiO)3AlOH occurs at mild temperatures and leads to
      the formation of AlFR Lewis sites tricoordinated to the zeolite framework. Al
      atoms of these (SiO)3Al Lewis sites exhibit an extremely broad (27)Al NMR
      resonance (deltai ~ 67 ppm, CQ ~ 20 MHz, and eta ~ 0.1).

PMID- 25393613
TI  - Clinical markers for identifying cholinergic deficits in Parkinson's disease.
AB  - BACKGROUND: Cholinergic projection systems degeneration is associated with
      dopamine nonresponsive features of Parkinson's disease (PD). Cholinergic deficits
      are variable in nondemented PD. Identification of cholinergic deficits in PD may
      help with selection of suitable patients for targeted cholinergic drug treatment
      in PD. The objective of this retrospective multivariate predictor analysis study
      was to identify clinical markers indicative of cholinergic deficits in PD
      patients, as assessed by acetylcholinesterase ([(11) C]PMP) positron emission
      tomography. METHODS: One hundred thirty-seven PD patients (34 female)
      participated; median modified Hoehn and Yahr score was 2.5 (range, 1-4), average
      age 65.6 +/- 7.4 years, and average duration of motor disease symptoms of 6.0 +/-
      4.2 years. Subjects were dichotomized as "normocholinergic" or "hypocholinergic"
      based on a 5(th) percentile cutoff from normal for the basal forebrain-cortical
      and pedunculopontine nucleus-thalamic cholinergic projection systems. Previously
      identified clinical indices of cholinergic denervation were used for statistical
      prediction of cholinergic deficits. Logistic regression determined which risk
      factors predicted cholinergic deficits. Sensitivity, specificity, and accuracy
      were determined for the (combinations of) significant predictor variables.
      RESULTS: Forty-nine (35.8%) hypocholinergic PD subjects were identified. The
      combination of rapid eye movement (REM) sleep behavior disorder (RBD) symptoms
      and fall history showed highest diagnostic accuracy (81.1%) for predicting
      combined thalamic and cortical cholinergic deficits. A combined assessment of 8.5
      m walk time and lower score on the Montreal cognitive assessment scale provided
      diagnostic accuracy of 80.7% for predicting isolated cortical cholinergic
      denervation. CONCLUSION: Assessment of clinical indices of cholinergic
      denervation may be useful for identifying suitable subjects for trials of
      targeted cholinergic drug treatments in PD.

PMID- 25393614
TI  - The sleeping beauty: how reproductive diapause affects hormone signaling,
      metabolism, immune response and somatic maintenance in Drosophila melanogaster.
AB  - Some organisms can adapt to seasonal and other environmental challenges by
      entering a state of dormancy, diapause. Thus, insects exposed to decreased
      temperature and short photoperiod enter a state of arrested development, lowered
      metabolism, and increased stress resistance. Drosophila melanogaster females can
      enter a shallow reproductive diapause in the adult stage, which drastically
      reduces organismal senescence, but little is known about the physiology and
      endocrinology associated with this dormancy, and the genes involved in its
      regulation. We induced diapause in D. melanogaster and monitored effects over 12
      weeks on dynamics of ovary development, carbohydrate and lipid metabolism, as
      well as expression of genes involved in endocrine signaling, metabolism and
      innate immunity. During diapause food intake diminishes drastically, but
      circulating and stored carbohydrates and lipids are elevated. Gene transcripts of
      glucagon- and insulin-like peptides increase, and expression of several target
      genes of these peptides also change. Four key genes in innate immunity can be
      induced by infection in diapausing flies, and two of these, drosomycin and
      cecropin A1, are upregulated by diapause independently of infection. Diapausing
      flies display very low mortality, extended lifespan and decreased aging of the
      intestinal epithelium. Many phenotypes induced by diapause are reversed after one
      week of recovery from diapause conditions. Furthermore, mutant flies lacking
      specific insulin-like peptides (dilp5 and dilp2-3) display increased diapause
      incidence. Our study provides a first comprehensive characterization of
      reproductive diapause in D. melanogaster, and evidence that glucagon- and insulin
      like signaling are among the key regulators of the altered physiology during this
      dormancy. 

PMID- 25393615
TI  - T-cell STAT3 is required for the maintenance of humoral immunity to LCMV.
AB  - STAT3 is a critical transcription factor activated downstream of cytokine
      signaling and is integral for the function of multiple immune cell types. Human
      mutations in STAT3 cause primary immunodeficiency resulting in impaired control
      of a variety of infections, including reactivation of latent viruses. In this
      study, we investigate how T-cell functions of STAT3 contribute to responses to
      viral infection by inducing chronic lymphocytic choriomeningitis virus (LCMV)
      infection in mice lacking STAT3 specifically in T cells. Although mice with
      conditional disruption of STAT3 in T cells were able to mount early responses to
      viral infection similar to control animals, including expansion of effector T
      cells, we found generation of T-follicular helper (Tfh) cells to be impaired. As
      a result, STAT3 T cell deficient mice produced attenuated germinal center
      reactions, and did not accumulate bone marrow virus specific IgG-secreting cells,
      resulting in failure to maintain levels of virus-specific IgG or mount
      neutralizing responses to LCMV in the serum. These effects were associated with
      reduced control of viral replication and prolonged infection. Our results
      demonstrate the importance of STAT3 in T cells for the generation of functional
      long-term humoral immunity to viral infections. 

PMID- 25393616
TI  - Arachidonic acid enhances reproduction in Daphnia magna and mitigates changes in
      sex ratios induced by pyriproxyfen.
AB  - Arachidonic acid is 1 of only 2 unsaturated fatty acids retained in the ovaries
      of crustaceans and an inhibitor of HR97g, a nuclear receptor expressed in adult
      ovaries. The authors hypothesized that, as a key fatty acid, arachidonic acid may
      be associated with reproduction and potentially environmental sex determination
      in Daphnia. Reproduction assays with arachidonic acid indicate that it alters
      female:male sex ratios by increasing female production. This reproductive effect
      only occurred during a restricted Pseudokirchneriella subcapitata diet. Next, the
      authors tested whether enriching a poorer algal diet (Chlorella vulgaris) with
      arachidonic acid enhances overall reproduction and sex ratios. Arachidonic acid
      enrichment of a C. vulgaris diet also enhances fecundity at 1.0 uM and 4.0 uM by
      30% to 40% in the presence and absence of pyriproxyfen. This indicates that
      arachidonic acid is crucial in reproduction regardless of environmental sex
      determination. Furthermore, the data indicate that P. subcapitata may provide a
      threshold concentration of arachidonic acid needed for reproduction. Diet-switch
      experiments from P. subcapitata to C. vulgaris mitigate some, but not all, of
      arachidonic acid's effects when compared with a C. vulgaris-only diet, suggesting
      that some arachidonic acid provided by P. subcapitata is retained. In summary,
      arachidonic acid supplementation increases reproduction and represses
      pyriproxyfen-induced environmental sex determination in D. magna in restricted
      diets. A diet rich in arachidonic acid may provide protection from some
      reproductive toxicants such as the juvenile hormone agonist pyriproxyfen. Environ
      Toxicol Chem 2015;34:527-535. (c) 2014 SETAC. 

PMID- 25393617
TI  - A Bayesian approach for instrumental variable analysis with censored time-to
      event outcome.
AB  - Instrumental variable (IV) analysis has been widely used in economics,
      epidemiology, and other fields to estimate the causal effects of covariates on
      outcomes, in the presence of unobserved confounders and/or measurement errors in
      covariates. However, IV methods for time-to-event outcome with censored data
      remain underdeveloped. This paper proposes a Bayesian approach for IV analysis
      with censored time-to-event outcome by using a two-stage linear model. A Markov
      chain Monte Carlo sampling method is developed for parameter estimation for both
      normal and non-normal linear models with elliptically contoured error
      distributions. The performance of our method is examined by simulation studies.
      Our method largely reduces bias and greatly improves coverage probability of the
      estimated causal effect, compared with the method that ignores the unobserved
      confounders and measurement errors. We illustrate our method on the Women's
      Health Initiative Observational Study and the Atherosclerosis Risk in Communities
      Study.

PMID- 25393618
TI  - Morphological and molecular characterization of a new Trichuris species (Nematoda
      Trichuridae), and phylogenetic relationships of Trichuris species of Cricetid
      rodents from Argentina.
AB  - Populations of Trichuris spp. isolated from six species of sigmodontine rodents
      from Argentina were analyzed based on morphological characteristics and ITS2
      (rDNA) region sequences. Molecular data provided an opportunity to discuss the
      phylogenetic relationships among the Trichuris spp. from Noth and South America
      (mainly from Argentina). Trichuris specimens were identified morphologically as
      Trichuris pardinasi, T. navonae, Trichuris sp. and Trichuris new species,
      described in this paper. Sequences analyzed by Maximum Parsimony, Maximum
      Likelihood and Bayesian inference methods showed four main clades corresponding
      with the four different species regardless of geographical origin and host
      species. These four species from sigmodontine rodents clustered together and
      separated from Trichuris species isolated from murine and arvicoline rodents
      (outgroup). Different genetic lineages observed among Trichuris species from
      sigmodontine rodents which supported the proposal of a new species. Moreover,
      host distribution showed correspondence with the different tribes within the
      subfamily Sigmodontinae. 

PMID- 25393619
TI  - Otitis media in sperm-associated antigen 6 (Spag6)-deficient mice.
AB  - Mammalian SPAG6 protein is localized to the axoneme central apparatus, and it is
      required for normal flagella and cilia motility. Recent studies demonstrated that
      the protein also regulates ciliogenesis and cilia polarity in the epithelial
      cells of brain ventricles and trachea. Motile cilia are also present in the
      epithelial cells of the middle ear and Eustachian tubes, where the ciliary system
      participates in the movement of serous fluid and mucus in the middle ear. Cilia
      defects are associated with otitis media (OM), presumably due to an inability to
      efficiently transport fluid, mucus and particles including microorganisms. We
      investigated the potential role of SPAG6 in the middle ear and Eustachian tubes
      by studying mice with a targeted mutation in the Spag6 gene. SPAG6 is expressed
      in the ciliated cells of middle ear epithelial cells. The orientation of the
      ciliary basal feet was random in the middle ear epithelial cells of Spag6
      deficient mice, and there was an associated disrupted localization of the planar
      cell polarity (PCP) protein, FZD6. These features are associated with disordered
      cilia orientation, confirmed by scanning electron microscopy, which leads to
      uncoordinated cilia beating. The Spag6 mutant mice were also prone to develop OM.
      However, there were no significant differences in bacterial populations,
      epithelial goblet cell density, mucin expression and Eustachian tube angle
      between the mutant and wild-type mice, suggesting that OM was due to accumulation
      of fluid and mucus secondary to the ciliary dysfunction. Our studies demonstrate
      a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in
      the regulation of cilia/basal body polarity through the PCP-dependent mechanisms
      in the middle ear and Eustachian tubes. 

PMID- 25393620
TI  - Association between footwear use and neglected tropical diseases: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The control of neglected tropical diseases (NTDs) has primarily
      focused on preventive chemotherapy and case management. Less attention has been
      placed on the role of ensuring access to adequate water, sanitation, and hygiene
      and personal preventive measures in reducing exposure to infection. Our aim was
      to assess whether footwear use was associated with a lower risk of selected NTDs.
      METHODOLOGY: We conducted a systematic review and meta-analysis to assess the
      association between footwear use and infection or disease for those NTDs for
      which the route of transmission or occurrence may be through the feet. We
      included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma,
      myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH)
      infections, particularly hookworm infection and strongyloidiasis. We searched
      Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases,
      contacted experts, and hand-searched reference lists for eligible studies. The
      search was conducted in English without language, publication status, or date
      restrictions up to January 2014. Studies were eligible for inclusion if they
      reported a measure of the association between footwear use and the risk of each
      NTD. Publication bias was assessed using funnel plots. Descriptive study
      characteristics and methodological quality of the included studies were
      summarized. For each study outcome, both outcome and exposure data were
      abstracted and crude and adjusted effect estimates presented. Individual and
      summary odds ratio (OR) estimates and corresponding 95% confidence intervals
      (CIs) were calculated as a measure of intervention effect, using random effects
      meta-analyses. PRINCIPAL FINDINGS: Among the 427 studies screened, 53 met our
      inclusion criteria. Footwear use was significantly associated with a lower odds
      of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI:
      0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48;
      95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84),
      strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95%
      CI: 0.37-0.94). No significant association between footwear use and podoconiosis
      (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma,
      myiasis, and snakebite. The main limitations were evidence of heterogeneity and
      poor study quality inherent to the observational studies included.
      CONCLUSIONS/SIGNIFICANCE: Our results show that footwear use was associated with
      a lower odds of several different NTDs. Access to footwear should be prioritized
      alongside existing NTD interventions to ensure a lasting reduction of multiple
      NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION:
      PROSPERO International prospective register of systematic reviews CRD42012003338.

PMID- 25393621
TI  - Quantitative proteomic analysis of serum from pregnant women carrying a fetus
      with conotruncal heart defect using isobaric tags for relative and absolute
      quantitation (iTRAQ) labeling.
AB  - OBJECTIVE: To identify differentially expressed proteins from serum of pregnant
      women carrying a conotruncal heart defects (CTD) fetus, using proteomic analysis.
      METHODS: The study was conducted using a nested case-control design. The 5473
      maternal serum samples were collected at 14-18 weeks of gestation. The serum from
      9 pregnant women carrying a CTD fetus, 10 with another CHD (ACHD) fetus, and 11
      with a normal fetus were selected from the above samples, and analyzed by using
      isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two
      dimensional liquid chromatography-tandem mass spectrometry(2D LC-MS/MS). The
      differentially expressed proteins identified by iTRAQ were further validated with
      Western blot. RESULTS: A total of 105 unique proteins present in the three groups
      were identified, and relative expression data were obtained for 92 of them with
      high confidence by employing the iTRAQ-based experiments. The downregulation of
      gelsolin in maternal serum of fetus with CTD was further verified by Western
      blot. CONCLUSIONS: The identification of differentially expressed protein
      gelsolin in the serum of the pregnant women carrying a CTD fetus by using
      proteomic technology may be able to serve as a foundation to further explore the
      biomarker for detection of CTD fetus from the maternal serum.

PMID- 25393623
TI  - Cloning of Gossypium hirsutum sucrose non-fermenting 1-related protein kinase 2
      gene (GhSnRK2) and its overexpression in transgenic Arabidopsis escalates drought
      and low temperature tolerance.
AB  - The molecular mechanisms of stress tolerance and the use of modern genetics
      approaches for the improvement of drought stress tolerance have been major
      focuses of plant molecular biologists. In the present study, we cloned the
      Gossypium hirsutum sucrose non-fermenting 1-related protein kinase 2 (GhSnRK2)
      gene and investigated its functions in transgenic Arabidopsis. We further
      elucidated the function of this gene in transgenic cotton using virus-induced
      gene silencing (VIGS) techniques. We hypothesized that GhSnRK2 participates in
      the stress signaling pathway and elucidated its role in enhancing stress
      tolerance in plants via various stress-related pathways and stress-responsive
      genes. We determined that the subcellular localization of the GhSnRK2-green
      fluorescent protein (GFP) was localized in the nuclei and cytoplasm. In contrast
      to wild-type plants, transgenic plants overexpressing GhSnRK2 exhibited increased
      tolerance to drought, cold, abscisic acid and salt stresses, suggesting that
      GhSnRK2 acts as a positive regulator in response to cold and drought stresses.
      Plants overexpressing GhSnRK2 displayed evidence of reduced water loss, turgor
      regulation, elevated relative water content, biomass, and proline accumulation.
      qRT-PCR analysis of GhSnRK2 expression suggested that this gene may function in
      diverse tissues. Under normal and stress conditions, the expression levels of
      stress-inducible genes, such as AtRD29A, AtRD29B, AtP5CS1, AtABI3, AtCBF1, and
      AtABI5, were increased in the GhSnRK2-overexpressing plants compared to the wild
      type plants. GhSnRK2 gene silencing alleviated drought tolerance in cotton
      plants, indicating that VIGS technique can certainly be used as an effective
      means to examine gene function by knocking down the expression of distinctly
      expressed genes. The results of this study suggested that the GhSnRK2 gene, when
      incorporated into Arabidopsis, functions in positive responses to drought stress
      and in low temperature tolerance. 

PMID- 25393622
TI  - Longitudinal analysis of T and B cell phenotype and function in renal transplant
      recipients with or without rituximab induction therapy.
AB  - BACKGROUND: Prevention of rejection after renal transplantation requires
      treatment with immunosuppressive drugs. Data on their in vivo effects on T- and B
      cell phenotype and function are limited. METHODS: In a randomized double-blind
      placebo-controlled study to prevent renal allograft rejection, patients were
      treated with tacrolimus, mycophenolate mofetil (MMF), steroids, and a single dose
      of rituximab or placebo during transplant surgery. In a subset of patients, we
      analyzed the number and phenotype of peripheral T and B cells by multiparameter
      flow cytometry before transplantation, and at 3, 6, 12, and 24 months after
      transplantation. RESULTS: In patients treated with tacrolimus/MMF/steroids the
      proportion of central memory CD4+ and CD8+ T cells was higher at 3 months post
      transplant compared to pre-transplant levels. In addition, the ratio between the
      percentage of central memory CD4+ and CD4+ regulatory T cells was significantly
      higher up to 24 months post-transplant compared to pre-transplant levels.
      Interestingly, treatment with tacrolimus/MMF/steroids resulted in a shift toward
      a more memory-like B-cell phenotype post-transplant. Addition of a single dose of
      rituximab resulted in a long-lasting B-cell depletion. At 12 months post
      transplant, the small fraction of repopulated B cells consisted of a high
      percentage of transitional B cells. Rituximab treatment had no effect on the T
      cell phenotype and function post-transplant. CONCLUSIONS: Renal transplant
      recipients treated with tacrolimus/MMF/steroids show an altered memory T and B
      cell compartment post-transplant. Additional B-cell depletion by rituximab leads
      to a relative increase of transitional and memory-like B cells, without affecting
      T-cell phenotype and function. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00565331.

PMID- 25393624
TI  - Resequencing and association analysis of PTPRA, a possible susceptibility gene
      for schizophrenia and autism spectrum disorders.
AB  - BACKGROUND: The PTPRA gene, which encodes the protein RPTP-alpha, is critical to
      neurodevelopment. Previous linkage studies, genome-wide association studies,
      controlled expression analyses and animal models support an association with both
      schizophrenia and autism spectrum disorders, both of which share a substantial
      portion of genetic risks. METHODS: We sequenced the protein-encoding areas of the
      PTPRA gene for single nucleotide polymorphisms or small insertions/deletions
      (InDel) in 382 schizophrenia patients. To validate their association with the
      disorders, rare (minor allele frequency <1%), missense mutations as well as one
      InDel in the 3'UTR region were then genotyped in another independent sample set
      comprising 944 schizophrenia patients, 336 autism spectrum disorders patients,
      and 912 healthy controls. RESULTS: Eight rare mutations, including 3 novel
      variants, were identified during the mutation-screening phase. In the following
      association analysis, L59P, one of the two missense mutations, was only observed
      among patients of schizophrenia. Additionally, a novel duplication in the 3'UTR
      region, 174620_174623dupTGAT, was predicted to be located within a Musashi
      Binding Element. MAJOR CONCLUSIONS: No evidence was seen for the association of
      rare, missense mutations in the PTPRA gene with schizophrenia or autism spectrum
      disorders; however, we did find some rare variants with possibly damaging effects
      that may increase the susceptibility of carriers to the disorders.

PMID- 25393625
TI  - Different expression of protein kinase A (PKA) regulatory subunits in normal and
      neoplastic thyroid tissues.
AB  - The four regulatory subunits (R1A, R1B, R2A, R2B) of protein kinase A (PKA) are
      differentially expressed in several cancer cell lines and exert distinct roles in
      both cell growth and cell differentiation control. Mutations of the PRKAR1A gene
      have been found in patients with Carney complex and in a minority of sporadic
      anaplastic thyroid carcinomas. The aim of the study was to retrospectively
      evaluate the expression of different PKA regulatory subunits in benign and non
      benign human thyroid tumours and to correlate their expression with clinical
      phenotype. Immunohistochemistry demonstrated a significant increase in PRKAR2B
      expression in both differentiated and undifferentiated (anaplastic) thyroid
      tumors in comparison with normal thyroid tissues. Conversely, a significant
      increase in PRKAR1A expression was only demonstrated in undifferentiated thyroid
      carcinomas in comparison with normal thyroid tissue and differentiated thyroid
      tumors. In thyroid cancers without lymph nodal metastases PRKAR1A expression was
      higher in tumours of more than 2 cm in size (T2 and T3) compared to smaller ones
      (T1). In conclusion, our data shows that an increased PRKAR1A expression is
      associated with aggressive and undifferentiated thyroid tumors.

PMID- 25393627
TI  - Are policy decisions on surgical procedures informed by robust economic evidence?
      A systematic review.
AB  - OBJECTIVES: The aim of this study was to examine the empirical and methodological
      cost-effectiveness evidence of surgical interventions for breast, colorectal, or
      prostate cancer. METHODS: A systematic search of seven databases including
      MEDLINE, EMBASE, and NHSEED, research registers, the NICE Web site and conference
      proceedings was conducted in April 2012. Study quality was assessed in terms of
      meeting essential, preferred and UK NICE specific requirements for economic
      evaluations. RESULTS: The seventeen (breast = 3, colorectal = 7, prostate = 7)
      included studies covered a broad range of settings (nine European; eight non
      European) and six were published over 10 years ago. The populations,
      interventions and comparators were generally well defined. Very few studies were
      informed by literature reviews and few used synthesized clinical evidence.
      Although the interventions had potential differential effects on recurrence and
      mortality rates, some studies used relatively short time horizons. Univariate
      sensitivity analyses were reported in all studies but less than a third
      characterized all uncertainty with a probabilistic sensitivity analysis. Although
      a third of studies incorporated patients' health-related quality of life data,
      only four studies used social tariff values. CONCLUSIONS: There is a dearth of
      recent robust evidence describing the cost-effectiveness of surgical
      interventions in the management of breast, colorectal and prostate cancers. Many
      of the recent publications did not satisfy essential methodological requirements
      such as using clinical evidence informed by a systematic review and synthesis.
      Given the ratio of potential benefit and harms associated with cancer surgery and
      the volume of resources consumed by these, there is an urgent need to increase
      economic evaluations of these technologies.

PMID- 25393626
TI  - Low dose cranial irradiation-induced cerebrovascular damage is reversible in
      mice.
AB  - BACKGROUND: High-dose radiation-induced blood-brain barrier breakdown contributes
      to acute radiation toxicity syndrome and delayed brain injury, but there are few
      data on the effects of low dose cranial irradiation. Our goal was to measure
      blood-brain barrier changes after low (0.1 Gy), moderate (2 Gy) and high (10 Gy)
      dose irradiation under in vivo and in vitro conditions. METHODOLOGY: Cranial
      irradiation was performed on 10-day-old and 10-week-old mice. Blood-brain barrier
      permeability for Evans blue, body weight and number of peripheral mononuclear and
      circulating endothelial progenitor cells were evaluated 1, 4 and 26 weeks
      postirradiation. Barrier properties of primary mouse brain endothelial cells co
      cultured with glial cells were determined by measurement of resistance and
      permeability for marker molecules and staining for interendothelial junctions.
      Endothelial senescence was determined by senescence associated beta-galactosidase
      staining. PRINCIPLE FINDINGS: Extravasation of Evans blue increased in cerebrum
      and cerebellum in adult mice 1 week and in infant mice 4 weeks postirradiation at
      all treatment doses. Head irradiation with 10 Gy decreased body weight. The
      number of circulating endothelial progenitor cells in blood was decreased 1 day
      after irradiation with 0.1 and 2 Gy. Increase in the permeability of cultured
      brain endothelial monolayers for fluorescein and albumin was time- and radiation
      dose dependent and accompanied by changes in junctional immunostaining for
      claudin-5, ZO-1 and beta-catenin. The number of cultured brain endothelial and
      glial cells decreased from third day of postirradiation and senescence in
      endothelial cells increased at 2 and 10 Gy. CONCLUSION: Not only high but low and
      moderate doses of cranial irradiation increase permeability of cerebral vessels
      in mice, but this effect is reversible by 6 months. In-vitro experiments suggest
      that irradiation changes junctional morphology, decreases cell number and causes
      senescence in brain endothelial cells.

PMID- 25393628
TI  - Liposomes modified with superhydrophilic polymer linked to a nonphospholipid
      anchor exhibit reduced complement activation and enhanced circulation.
AB  - We report the synthesis of an acyl-anchored superhydrophilic polymer (SHP) for
      external surface modification of liposome surface. N1-(2-aminoethyl)-N4-hexadecyl
      2-tetradecylsuccinamide conjugated with SHP (HDAS-SHP) was synthesized and used
      for modifying the liposome surface. Unlike polyethylene glycol (PEG)
      phospholipids, which are commonly used for manufacturing stealth liposomes, HDAS
      SHP is devoid of both PEG and phosphoryl groups and possesses a zwitterionic
      polymeric chain. Circulation persistence of the 99(m)Tc-labeled HDAS-SHP
      liposomes was documented by gamma camera imaging. After 24 h postinjection,
      approximately 30% of injected HDAS-SHP liposomes were present in blood as
      compared with only 4.5% of the plain liposomes. HDAS-SHP liposomes inhibited
      complement activation. They were found to be amenable to pH-gradient-based active
      loading of Adriamycin in a stable manner. At 37 degrees C, HDAS-SHP liposomes
      provided better encapsulation efficiencies than the liposomes modified with DSPE
      PEG2000. These results provide a strong basis for HDAS-SHP as a viable
      alternative to PEG-phospholipids for imparting stealth characteristics to drug
      delivery vehicles such as liposomes. (c) 2014 Wiley Periodicals, Inc. and the
      American Pharmacists Association J Pharm Sci 104:114-123, 2015.

PMID- 25393629
TI  - Impacts of diffuse radiation on light use efficiency across terrestrial
      ecosystems based on Eddy covariance observation in China.
AB  - Ecosystem light use efficiency (LUE) is a key factor of production models for
      gross primary production (GPP) predictions. Previous studies revealed that
      ecosystem LUE could be significantly enhanced by an increase on diffuse
      radiation. Under large spatial heterogeneity and increasing annual diffuse
      radiation in China, eddy covariance flux data at 6 sites across different
      ecosystems from 2003 to 2007 were used to investigate the impacts of diffuse
      radiation indicated by the cloudiness index (CI) on ecosystem LUE in grassland
      and forest ecosystems. Our results showed that the ecosystem LUE at the six sites
      was significantly correlated with the cloudiness variation (0.24 <= R(2) <=
      0.85), especially at the Changbaishan temperate forest ecosystem (R(2) = 0.85).
      Meanwhile, the CI values appeared more frequently between 0.8 and 1.0 in two
      subtropical forest ecosystems (Qianyanzhou and Dinghushan) and were much larger
      than those in temperate ecosystems. Besides, cloudiness thresholds which were
      favorable for enhancing ecosystem carbon sequestration existed at the three
      forest sites, respectively. Our research confirmed that the ecosystem LUE at the
      six sites in China was positively responsive to the diffuse radiation, and the
      cloudiness index could be used as an environmental regulator for LUE modeling in
      regional GPP prediction.

PMID- 25393630
TI  - The association between meteorological parameters and aneurysmal subarachnoid
      hemorrhage: a nationwide analysis.
AB  - Prior research has suggested that regional weather patterns impact the risk of
      rupture of cerebral aneurysms, but the findings in the literature have been
      inconsistent. Furthermore, no nationwide analysis to date has examined the
      association between meteorological factors and the post-procedural outcomes of
      patients after the treatment for ruptured cerebral aneurysms. The purpose of this
      study was to use a nationwide sample to analyze the association between specific
      meteorological parameters--temperature, precipitation, sunlight, and humidity-
      and hospital admission rate for and outcome after aneurysmal subarachnoid
      hemorrhage. Patients were identified using the Nationwide Inpatient Sample (2001
      2010): Those with an ICD-9 diagnosis code for subarachnoid hemorrhage and a
      procedural code for aneurysm repair were included. Climate data were obtained
      from the State of the Climate Report 2010 released by the National Climatic Data
      Center. Multivariate regression models were constructed to analyze the
      association between average state monthly temperature, precipitation, and percent
      possible sunlight, as well as relative morning humidity and both monthly hospital
      admission rate, adjusted for annual state population in millions, and in-hospital
      mortality. 16,970 admissions were included from 723 hospitals across 41 states.
      Decreased daily sunlight and lower relative humidity were associated with an
      increased rate of admission for ruptured cerebral aneurysms (p<0.001), but had no
      association with differential inpatient mortality. No significant changes in
      these observed associations were seen when multivariate analyses were
      constructed. This is the first nationwide study to suggest that decreased
      sunlight and lower relative humidity are associated with admission for ruptured
      cerebral aneurysms. While it has been postulated that external atmospheric
      factors may cause hormonal and homeostatic changes that impact the risk of
      rupture of cerebral aneurysms, additional research is needed to confirm and
      further understand these relationships.

PMID- 25393632
TI  - The sudden vector projection model for reactivity: mode specificity and bond
      selectivity made simple.
AB  - CONSPECTUS: Mode specificity is defined by the differences in reactivity due to
      excitations in various reactant modes, while bond selectivity refers to selective
      bond breaking in a reaction. These phenomena not only shed light on reaction
      dynamics but also open the door for laser control of reactions. The existence of
      mode specificity and bond selectivity in a reaction indicates that not all forms
      of energy are equivalent in promoting the reactivity, thus defying a statistical
      treatment. They also allow the enhancement of reactivity and control product
      branching ratio. As a result, they are of central importance in chemistry. This
      Account discusses recent advances in our understanding of these nonstatistical
      phenomena. In particular, the newly proposed sudden vector projection (SVP) model
      and its applications are reviewed. The SVP model is based on the premise that the
      collision in many direct reactions is much faster than intramolecular vibrational
      energy redistribution in the reactants. In such a sudden limit, the coupling of a
      reactant mode with the reaction coordinate at the transition state, which
      dictates its ability to promote the reaction, is approximately quantified by the
      projection of the former onto the latter. The SVP model can be considered as a
      generalization of the venerable Polanyi's rules, which are based on the location
      of the barrier. The SVP model is instead based on properties of the saddle point
      and as a result capable of treating the translational, rotational, and multiple
      vibrational modes in reactions involving polyatomic reactants. In case of surface
      reactions, the involvement of surface atoms can also be examined. Taking
      advantage of microscopic reversibility, the SVP model has also been used to
      predict product energy disposal in reactions. This simple yet powerful rule of
      thumb has been successfully demonstrated in many reactions including uni- and
      bimolecular reactions in the gas phase and gas-surface reactions. The success of
      the SVP model underscores the importance of the transition state in controlling
      mode-specific and bond-selective chemistry.

PMID- 25393631
TI  - Chronic kidney disease and risk of renal cell carcinoma: differences by race.
AB  - BACKGROUND: The incidence of renal cell carcinoma in the United States differs by
      race/ethnicity. To better understand these disparities, we conducted a nested
      case-control study investigating renal cell carcinoma risk factors across
      racial/ethnic groups within the Kaiser Permanente Northern California health care
      network. METHODS: Our study included 3136 renal cell carcinoma cases (2152
      whites, 293 blacks, 425 Hispanics, and 255 Asians) diagnosed between 1998 and
      2008 and 31031 individually matched controls (21478 whites, 2836 blacks, 4147
      Hispanics, and 2484 Asians). Risk of renal cell carcinoma was assessed in
      relation to smoking status, body mass index (BMI), hypertension, and chronic
      kidney disease. We calculated odds ratios (ORs) and 95% confidence intervals
      (CIs) using conditional logistic regression, and population attributable risk
      (PAR) to estimate by race the proportion of cases attributable to hypertension
      and chronic kidney disease. RESULTS: The association between chronic kidney
      disease and renal cell carcinoma differed markedly by race (Pinteraction <
      0.001), with associations observed among blacks (OR = 10.4 [95% CI = 6.0-17.9]),
      Asians (5.1 [2.2-11.7]), and Hispanics (2.3 [1.1-4.6]) but not whites (1.1 [0.6
      1.9]). Hypertension, high BMI, and smoking were associated with renal cell
      carcinoma, but findings generally did not differ by race. Relative to other
      racial/ethnic groups, blacks had the highest proportion of renal cell carcinoma
      incidence attributable to hypertension and chronic kidney disease (combined, PAR
      = 37%; hypertension only, PAR = 27%; chronic kidney disease, PAR = 10%).
      CONCLUSIONS: Our findings suggest that hypertension and chronic kidney disease
      likely have contributed to the observed excess in renal cell carcinoma incidence
      among blacks compared with whites.

PMID- 25393633
TI  - The evolution of breast cancer navigation and survivorship care.
AB  - Over the last several decades, breast screening, diagnosis, and treatment have
      evolved. With that evolutionary process, so have the complexities of oncology
      care, especially from the perspective of more fragmented care occurring. The
      majority of breast care is outpatient based. The need for patient navigation has
      heightened as this fragmentation and financial issues set before the oncologist
      and the patient continue to occur and in many situations increase. Without
      effective navigation, breast patients can fall through the cracks and not get
      diagnosed as early as possible, or not receive all appropriate treatment they
      need. We are also seeing a steady increase in the actual number of breast cancer
      patients being diagnosed and surviving long term. Unfortunately simultaneous to
      this happen there is also a growing shortage of oncology specialists in the USA.
      This results in a need to transition survivors back to their community physicians
      after the completion of their acute treatment, and to do so in an organized,
      anticipated manner that prepares the survivor and her PCP and gynecologist, the
      tools they all need for effective cancer survivorship management. 

PMID- 25393634
TI  - The Manchester Uveitis Clinic: The first 3000 patients, 2: Uveitis
      Manifestations, Complications, Medical and Surgical Management.
AB  - PURPOSE: To demonstrate the manifestations and complications of uveitis, and
      their medical and surgical management, in a very large group of patients
      attending the Manchester Uveitis Clinic (MUC), a specialist uveitis clinic in the
      Northwest of England, UK. METHODS: Retrospective retrieval of data on a
      computerized database incorporating all new referrals to MUC from 1991 to 2013.
      RESULTS: A total of 3000 new patients with uveitis were seen during a 22-year
      period, of which 25.2% had a single acute episode, 13.6% had acute recurrent
      uveitis, 20.2% had chronic fluctuating uveitis, and 41.0% had chronic unremitting
      uveitis. The commonest complications were cataract (35% of patients), macular
      edema (20.5%), and glaucoma (19.5%). Oral steroids were required in 36% of
      patients, oral immunosuppression in 16%, and biologic treatment in 2%. Major
      intraocular surgery was required in 28%. CONCLUSIONS: Oral steroid usage is not
      an independent risk factor for cataract formation in patients with uveitis. Oral
      immunosuppression usage has increased 4-fold during this study period.

PMID- 25393635
TI  - From vitamin K antagonists to liver international normalized ratio: a historical
      journey and critical perspective.
AB  - Adoption of international normalized ratio (INR) to harmonize prothrombin time
      has greatly improved the safety and effectiveness of vitamin K antagonists (VKA)
      oral anticoagulant therapy. INR is also a major laboratory variable in
      calculating the widely used Model for End-Stage Liver Disease (MELD) score for
      liver transplant organ prioritization. However, since the conventional INR
      (INRVKA) is calibrated specifically for VKA patients, its interlaboratory
      variation has a significant impact on the accuracy of MELD score. Though still
      requiring further clinical validation in large numbers of waitlisted patients,
      the alternative liver INR calibrated by using plasma from liver disease patients
      instead of VKA patients may harmonize the differences and thus more suitable for
      MELD score calculation. The objective of this article is to review the history of
      INR, MELD score, and liver INR, and discuss the challenges and solutions of liver
      INR implementation. 

PMID- 25393636
TI  - Mast cell-derived heparin proteoglycans as a model for a local antithrombotic.
AB  - Mast cell-derived heparin proteoglycans (HEP-PG) reside in vascular tissue and
      serve as a local antithrombotic. Heparin, as used clinically, is isolated from
      its protein backbone from porcine and bovine gut mucosa. The isolated heparin is
      an anticoagulant; however, when bound to a protein carrier the heparin conjugates
      will become antiplatelet agents by inhibiting collagen-induced platelet
      aggregation and procoagulant activity, as distinct from soluble heparin. HEP-PG,
      whether soluble or immobilized to a surface, inhibit platelet deposition on the
      collagen surface in flowing blood. Mimics of HEP-PG, can be tailored to molecules
      carrying both antiplatelet and anticoagulant (APAC) properties. These molecules
      can target the vascular injury site and take residence there. Inhibition of
      thrombus growth using these APACs under these conditions has been demonstrated in
      several animal models. Although efficacious for antiplatelet and anticoagulant
      effects, the bleeding time is shorter with APACs than with unfractionated
      heparin, suggestive of beneficial efficacy/safety ratio. These strategies may be
      utilized in drug development, where many vascular injury-related problems can be
      tackled locally. 

PMID- 25393637
TI  - Short term preservation of hide using vacuum: influence on properties of hide and
      of processed leather.
AB  - The objective of this work was to investigate vacuum influence on hide
      preservation time and how it affects hide structure. It was established that
      vacuum prolongs the storage time without hide tissue putrefaction up to 21 days
      when the storage temperature is 4 degrees C. The microorganisms act for all
      storage times, but the action is weak and has no observable influence on the
      quality of hide during the time period mentioned. The hide shrinkage temperature
      decrease is negligible, which shows that breaking of intermolecular bonds does
      not occur. Optical microscopy, infrared spectroscopy and differential scanning
      calorimetry also did not show any structural changes which can influence the
      quality of leather produced from such hide. The qualitative indexes of wet blue
      processed under laboratory conditions and of leather produced during industrial
      trials are presented. Indexes such as chromium compounds exhaustion, content of
      chromium in leather, content of soluble matter in dichloromethane, strength
      properties, and shrinkage temperature were determined. Properties of the leather
      produced from vacuumed hide under industrial conditions conformed to the
      requirements of shoe upper leather. 

PMID- 25393638
TI  - Exploring parent-child discussions of crime and their influence on children's
      memory.
AB  - When children witness or experience criminal events, the first people they go to
      are generally parents. Typically, no one else is privy to these conversations,
      and consequently little is known about their specific content. Research has shown
      that children can be quite accurate witnesses at times. However, they can also
      incorporate information from misleading and suggestive questions into their
      recall, and once their event memory has been changed, children may be unable to
      provide accurate reports. It is important then to assess parent-child discussions
      about crime. In the present study, 7- to 10-year-old children watched a video of
      a theft and talked about it with a parent immediately afterwards, and half had a
      second immediate interview with a researcher. All were interviewed by a different
      interviewer 1 week later. Results showed that: parents relied on direct and
      yes/no questions; children made errors of commission in response to questions;
      some parents asked leading or misleading questions; children incorporated all
      correct information from leading questions and nearly 40% of incorrect
      information from misleading questions; children provided additional information
      when interviewed by an interviewer 1 week later; and children remained relatively
      accurate in their descriptions but some were more accurate with parents than with
      an interviewer 1 week later.

PMID- 25393639
TI  - Proteomics of follicular fluid from women with polycystic ovary syndrome suggests
      molecular defects in follicular development.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS), a major cause of anovulatory
      infertility, is characterized by arrested follicular growth. Altered protein
      levels in the follicular fluid surrounding the ovum may reflect the molecular
      defects of folliculogenesis in these women. OBJECTIVE: To identify differentially
      regulated proteins in PCOS by comparing the follicular fluid protein repertoire
      of PCOS with healthy women. METHODS: The follicular fluid samples were collected
      from PCOS and normo-ovulatory women undergoing in vitro fertilization. Follicular
      fluid proteins were subjected to digestion using trypsin, and resultant peptides
      were labeled with isobaric tags for relative and absolute quantification reagents
      and analyzed by liquid chromatography tandem mass spectrometry. Differential
      abundance of selected proteins was confirmed by ELISA. RESULTS: A total of 770
      proteins were identified, of which 186 showed differential abundance between
      controls and women with PCOS. Proteins involved in various processes of
      follicular development including amphiregulin; heparan sulfate proteoglycan 2;
      tumor necrosis factor, alpha-induced protein 6; plasminogen; and lymphatic vessel
      endothelial hyaluronan receptor 1 were found to be deregulated in PCOS. We also
      identified a number of new proteins from follicular fluid, whose function in the
      ovary is not yet clearly established. These include suprabasin; S100 calcium
      binding protein A7; and helicase with zinc finger 2, transcriptional coactivator.
      CONCLUSIONS: Proteins indispensable for follicular growth were found to be
      differentially expressed in follicular fluid of women with PCOS, which may in
      part explain the aberrant folliculogenesis observed in these women.

PMID- 25393640
TI  - Liraglutide reduces oxidative stress and restores heme oxygenase-1 and ghrelin
      levels in patients with type 2 diabetes: a prospective pilot study.
AB  - CONTEXT: Liraglutide is a glucagon-like peptide-1 analog and glucose-lowering
      agent whose effects on cardiovascular risk markers have not been fully
      elucidated. OBJECTIVE: We evaluated the effect of liraglutide on markers of
      oxidative stress, heme oxygenase-1 (HO-1), and plasma ghrelin levels in patients
      with type-2 diabetes mellitus (T2DM). DESIGN AND SETTING: A prospective pilot
      study of 2 months' duration has been performed at the Unit of Diabetes and
      Cardiovascular Prevention at University of Palermo, Italy. Patients and
      Intervention(s): Twenty subjects with T2DM (10 men and 10 women; mean age: 57 +/-
      13 y) were treated with liraglutide sc (0.6 mg/d for 2 wk, followed by 1.2 mg/d)
      in addition to metformin (1500 mg/d orally) for 2 months. Patients with liver
      disorders or renal failure were excluded. MAIN OUTCOME MEASURE(S): Plasma ghrelin
      concentrations, oxidative stress markers, and heat-shock proteins, including HO-1
      were assessed. RESULTS: The addition of liraglutide resulted in a significant
      decrease in glycated hemoglobin (HbA1c) (8.5 +/- 0.4 vs 7.5 +/- 0.4%, P < .0001).
      In addition, plasma ghrelin and glutathione concentrations increased (8.2 +/- 4.1
      vs 13.6 +/- 7.3 pg/ml, P = .0007 and 0.36 +/- 0.06 vs 0.44 +/- 0.07 nmol/ml, P =
      .0002, respectively), whereas serum lipid hydroperoxides and HO-1 decreased (0.11
      +/- 0.05 vs 0.04 +/- 0.07 pg/ml, P = .0487 and 7.7 +/- 7.7 vs 3.6 +/- 1.8 pg/ml,
      P = .0445, respectively). These changes were not correlated with changes in
      fasting glycemia or HbA1c. CONCLUSIONS: In a 2-months prospective pilot study,
      the addition of liraglutide to metformin resulted in improvement in oxidative
      stress as well as plasma ghrelin and HO-1 concentrations in patients with T2DM.
      These findings seemed to be independent of the known effects of liraglutide on
      glucose metabolism.

PMID- 25393641
TI  - Sex steroids, precursors, and metabolite deficiencies in men with isolated
      hypogonadotropic hypogonadism and panhypopituitarism: a GCMS-based comparative
      study.
AB  - CONTEXT: Both testicular and adrenal steroid secretions are impaired in men with
      panhypopituitarism (Hypo-Pit), whereas only testicular steroid secretion is
      impaired in men with isolated gonadotropin deficiency (IHH) caused by normosmic
      congenital hypogonadotropic hypogonadism or Kallmann syndrome. OBJECTIVE: The
      objective of the study was to compare the serum levels of sex steroids,
      precursors, and metabolites between men with complete IHH and those with Hypo
      Pit. PATIENTS: We studied 42 healthy men, 16 untreated men with IHH (normosmic
      congenital hypogonadotropic hypogonadism/Kallmann syndrome) and 23 men with Hypo
      Pit (14 with craniopharyngioma, 9 with congenital hypopituitarism) receiving
      hydrocortisone, thyroxine, and GH replacement therapy but not T. METHODS: Gas
      chromatography/mass spectrometry (GCMS) was used to measure the serum levels of
      sex steroids [T, dihydrotestosterone (DHT), and estradiol (E2)], their precursors
      (pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenediol,
      progesterone, 17-hydroxyprogesterone, and androstenedione), and their metabolites
      (androsterone, estrone, and estrone sulfate) as well as pregnenolone and
      dehydroepiandrosterone sulfate esters. RESULTS: All the above-mentioned steroids,
      and notably T, DHT, and E2, were significantly lower in IHH patients than in
      controls but remained well above the detection limit of the relevant assays. In
      Hypo-Pit men, all these steroids were dramatically and significantly lower than
      in IHH. Interestingly, T, DHT, and E2, as well as pregnenolone and
      dehydroepiandrosterone sulfate esters, were undetectable or barely detectable in
      the Hypo-Pit men. CONCLUSIONS: Steroid deficiencies are marked but partial in men
      with complete IHH. In contrast, men with Hypo-Pit have a very severe overall
      steroid deficiency. These deficiencies could affect health and quality of life.

PMID- 25393642
TI  - Total body fat and central fat mass independently predict insulin resistance but
      not hyperandrogenemia in women with polycystic ovary syndrome.
AB  - CONTEXT/OBJECTIVE: Obesity is a common feature of women with polycystic ovary
      syndrome (PCOS). The aim of this study was to assess the role of body fat on
      insulin resistance and androgen excess in these subjects. PATIENTS/DESIGN: One
      hundred sixteen consecutive Caucasian women with PCOS, diagnosed by the Rotterdam
      criteria, underwent accurate assessment of clinical, anthropometric, hormonal,
      and metabolic features. In particular, total fat mass and fat distribution were
      assessed by dual-energy x-ray absorptiometry, serum-free T by liquid
      chromatography mass spectrometry and equilibrium dialysis and insulin sensitivity
      by the glucose clamp technique. RESULTS: Total fat mass and truncal fat were
      significantly higher in insulin-resistant than in insulin-sensitive PCOS subjects
      (+89% and +127%, respectively, both P < .001), and both tended to be higher in
      hyperandrogenemic than in normoandrogenemic women (+22% and +28%, respectively, P
      = .087 and P = .090). All parameters of adiposity correlated inversely with
      insulin sensitivity (P < .001) and directly with serum-free T (P <= .001). A
      statistically significant inverse relationship was observed between insulin
      sensitivity and serum-free T concentrations (r = -0.527, P < .001). In a multiple
      regression analysis, either total fat mass or truncal fat, in addition to serum
      free T and age, were independent predictors of insulin sensitivity. However,
      insulin sensitivity, but not total fat mass or truncal fat, was an independent
      predictor of free T concentrations. CONCLUSIONS: These data suggest that body fat
      contributes to determining insulin resistance in PCOS women. However, the
      association between body fat and hyperandrogenism seems to be to a large extent
      explained by insulin resistance.

PMID- 25393643
TI  - Cancer-related worry in Canadian thyroid cancer survivors.
AB  - CONTEXT: Little is known about cancer-related worry in thyroid cancer survivors.
      OBJECTIVES: We quantified cancer-related worry in Canadian thyroid cancer
      survivors and explored associated factors. DESIGN, SETTING, AND PARTICIPANTS: We
      performed a cross-sectional, self-administered, written survey of thyroid cancer
      survivor members of the Thyroid Cancer Canada support group. Independent factors
      associated with cancer-related worry were identified using a multivariable linear
      regression analysis. MAIN OUTCOME MEASURE: We used the Assessment of Survivor
      Concerns (ASC) questionnaire, which includes questions on worry about diagnostic
      tests, second primary malignancy, recurrence, dying, health, and children's
      health. RESULTS: The response rate for eligible members was 60.1% (941 of 1567).
      Most respondents were women (89.0%; 837 of 940), and the age was < 50 years in
      54.0% of participants (508 of 941). Thyroid cancer was diagnosed within <= 5
      years in 66.1% of participants (622 of 940). The mean overall ASC score was 15.34
      (SD, 4.7) (on a scale from 6 [least worry] to 24 [most worry]). Factors
      associated with increased ASC score included: younger age (P < .001), current
      suspected or proven recurrent/persistent disease (ie, current proven active
      disease or abnormal diagnostic tests) (P < .001), partnered marital status (P =
      .021), having children (P = .029), and <=5 years since thyroid cancer diagnosis
      (P = .017). CONCLUSIONS: In a population of Canadian thyroid cancer survivors,
      cancer-related worry was greatest in younger survivors and those with either
      confirmed or suspected disease activity. Family status and time since thyroid
      cancer diagnosis were also associated with increased worry. More research is
      needed to confirm these findings and to develop effective preventative and
      supportive strategies for those at risk.

PMID- 25393644
TI  - 11beta-Hydroxysteroid dehydrogenase activity in the brain does not contribute to
      systemic interconversion of cortisol and cortisone in healthy men.
AB  - CONTEXT AND OBJECTIVE: 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1)
      catalyses regeneration of cortisol in liver, adipose tissue, and skeletal muscle,
      making a substantial contribution to circulating cortisol as demonstrated in
      humans by combining stable isotope tracer infusion with arteriovenous sampling.
      In the brain, 11betaHSD1 is a potential therapeutic target implicated in age
      associated cognitive dysfunction. We aimed to quantify brain 11betaHSD1 activity,
      both to assess its contribution to systemic cortisol/cortisone turnover and to
      develop a tool for measuring 11betaHSD1 in dementia and following administration
      of 11betaHSD1 inhibitors. DESIGN, SETTING, AND PARTICIPANTS: With ethical
      approval and informed consent, 8 healthy men aged 38.1 years (sd 16.5) underwent
      an ECG-gated phase-contrast magnetic resonance scan to quantify internal jugular
      vein blood flow and were infused with 1,2 [(2)H]2-cortisone and 9,11,12,12
      [(2)H]4-cortisol for 3 h before samples were obtained from the internal jugular
      vein and an arterialized hand vein. Steroids were quantified by liquid
      chromatography-tandem mass spectrometry. MAIN OUTCOME MEASURES AND RESULTS:
      Steady state tracer enrichments were achieved and systemic indices of
      cortisol/cortisone interconversion were consistent with previous studies in
      healthy men. However, there was no measurable release or production of cortisol,
      9,12,12 [(2)H]3-cortisol or cortisone into the internal jugular vein.
      CONCLUSIONS: Although cerebral 11betaHSD1 reductase activity may be greater in
      cognitively impaired patients, in healthy men any contribution of 11betaHSD1 in
      the brain to systemic cortisol/cortisone turnover is negligible. The influence of
      11betaHSD1 in the brain is likely confined to subregions, notably the
      hippocampus. Alternative approaches are required to quantify pharmacodynamics
      effects of 11betaHSD1 inhibitors in the human brain.

PMID- 25393645
TI  - Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on
      bone mineral density in postmenopausal women with osteoporosis.
AB  - CONTEXT: Abaloparatide is a novel synthetic peptide analog of parathyroid hormone
      related protein (PTHrP) that is currently being developed as a potential anabolic
      agent in the treatment of postmenopausal osteoporosis. OBJECTIVE: This study
      sought to assess the effects of abaloparatide on bone mineral density (BMD) at
      the lumbar spine, total hip, and femoral neck in postmenopausal women with
      osteoporosis. DESIGN: Multi-center, multi-national, double-blind placebo
      controlled trial in which postmenopausal women were randomly assigned to receive
      24 weeks of treatment with daily sc injections of placebo, abaloparatide, 20, 40,
      or 80 MUg, or teriparatide, 20 MUg. A 24-week extension was also performed in a
      subset of subjects. PARTICIPANTS: Postmenopausal women with osteoporosis (n =
      222). MAIN OUTCOME MEASURES: BMD by dual-x-ray absorptiometry and biochemical
      markers of bone turnover. RESULTS: At 24 weeks, lumbar spine BMD increased by
      2.9, 5.2, and 6.7% in the abaloparatide, 20-, 40-, and 80-MUg groups,
      respectively, and 5.5% in the teriparatide group. The increases in the 40- and 80
      MUg abaloparatide groups and the teriparatide group were significantly greater
      than placebo (1.6%). Femoral neck BMD increased by 2.7, 2.2, and 3.1% in
      abaloparatide, 20-, 40-, and 80-MUg groups, respectively, and 1.1% in the
      teriparatide group. The increase in femoral neck BMD with abaloparatide, 80 MUg
      was significantly greater than placebo (0.8%). Total hip BMD increased by 1.4,
      2.0, and 2.6% in the abaloparatide, 20-, 40-, and 80-MUg groups, respectively.
      The total hip increases in the 40- and 80-MUg abaloparatide groups were greater
      than both placebo (0.4%) and teriparatide (0.5%). CONCLUSIONS: Compared with
      placebo, 24 weeks of daily sc abaloparatide increases BMD of the lumbar spine,
      femoral neck, and total hip in a dose-dependent fashion. Moreover, the
      abaloparatide-induced BMD increases at the total hip are greater than with the
      marketed dose of teriparatide. These results support the further investigation of
      abaloparatide as an anabolic therapy in postmenopausal osteoporosis.

PMID- 25393647
TI  - Solid state isostructural behavior and quantified limiting substitution kinetics
      in Schiff-base bidentate ligand complexes fac-[Re(O,N-Bid)(CO)3(MeOH)](n).
AB  - A range of N,O-donor atom salicylidene complexes of the type fac-[M(O,N
      Bid)(CO)3(L)](n) (O,N-Bid = anionic N,O-bidentate ligands; L = neutral
      coordinated ligand) have been studied. The unique feature of the complexes which
      crystallize in a monoclinic isostructural space group for complexes containing
      methanol in the sixth position (L = MeOH) is highlighted. The reactivity and
      stability of the complexes were evaluated by rapid stopped-flow techniques, and
      the methanol substitution by a range of pyridine type ligands indicates
      significant activation by the N,O-salicylidene type of bidentate ligands as
      observed from the variation in the second-order rate constants. In particular,
      following the introduction of the sterically demanding and electron rich
      cyclohexyl salicylidene moiety on the bidentate ligand, novel limiting kinetic
      behavior is displayed by all entering ligands, thus enabling a systematic probe
      and manipulation of the limiting kinetic constants. Clear evidence of an
      interchange type of intimate mechanism for the methanol substitution is produced.
      The equilibrium and rate constants (25  degrees C) for the two steps in the
      dissociative interchange mechanism for methanol substitution in fac-[Re(Sal
      Cy)(CO)3(MeOH)] (5) by the pyridine type ligands 3-chloropyridine, pyridine, 4
      picoline, and DMAP are k3 (s(-1)), 40 +/- 4, 13 +/- 2, 10.4 +/- 0.7, and 2.11 +/-
      0.09, and K2 (M(-1)), 0.13 +/- 0.01, 0.21 +/- 0.03, 0.26 +/- 0.02, and 1.8 +/-
      0.1, respectively. 

PMID- 25393646
TI  - Binding mode and potency of N-indolyloxopyridinyl-4-aminopropanyl-based
      inhibitors targeting Trypanosoma cruzi CYP51.
AB  - Chagas disease is a chronic infection in humans caused by Trypanosoma cruzi and
      manifested in progressive cardiomyopathy and/or gastrointestinal dysfunction.
      Limited therapeutic options to prevent and treat Chagas disease put 8 million
      people infected with T. cruzi worldwide at risk. CYP51, involved in the
      biosynthesis of the membrane sterol component in eukaryotes, is a promising drug
      target in T. cruzi. We report the structure-activity relationships (SAR) of an N
      arylpiperazine series of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors
      designed to probe the impact of substituents in the terminal N-phenyl ring on
      binding mode, selectivity and potency. Depending on the substituents at C-4, two
      distinct ring binding modes, buried and solvent-exposed, have been observed by X
      ray structure analysis (resolution of 1.95-2.48 A). The 5-chloro-substituted
      analogs 9 and 10 with no substituent at C-4 demonstrated improved selectivity and
      potency, suppressing >= 99.8% parasitemia in mice when administered orally at 25
      mg/kg, b.i.d., for 4 days.

PMID- 25393650
TI  - Synthesis of nitrogen-doped mesoporous carbon spheres with extra-large pores
      through assembly of diblock copolymer micelles.
AB  - The synthesis of highly nitrogen-doped mesoporous carbon spheres (NMCS) is
      reported. The large pores of the NMCS were obtained through self-polymerization
      of dopamine (DA) and spontaneous co-assembly of diblock copolymer micelles. The
      resultant narrowly dispersed NMCS possess large mesopores (ca. 16 nm) and small
      particle sizes (ca. 200 nm). The large pores and small dimensions of the N
      heteroatom-doped carbon spheres contribute to the mass transportation by reducing
      and smoothing the diffusion pathways, leading to high electrocatalytic activity. 

PMID- 25393649
TI  - Mobilization in severe sepsis: an integrative review.
AB  - Severe sepsis is a leading cause of long-term morbidity in the United States. Up
      to half of severe sepsis is treated in non-intensive care unit (ICU) settings,
      making it applicable to hospitalist practice. Evidence has demonstrated benefits
      from physical therapy (PT) in myriad conditions; whether PT may benefit severe
      sepsis patients either within or outside the ICU is unknown. Therefore, we
      conducted a review of the literature to understand whether early mobilization
      improves outcomes in patients with severe sepsis in non-ICU settings. We
      summarized the pathophysiology of functional decline in severe sepsis, the
      efficacy of PT in other patient populations, and the potential rationale for PT
      interventions in patients with severe sepsis. Multiple databases were searched
      for keywords including length of stay, mortality,costs, mobilization, and PT. Two
      authors (S.G. and V.C.) independently determined the eligibility of each study.A
      secondary review including studies of any infectious pathology with PT
      interventions or sepsis patients within the ICU was also conducted. Our search
      did not yield any primary literature regarding the impact of mobilization on
      severe sepsis outcomes in non-ICU settings. Only 1 retrospective study showed
      potential benefit of therapy in sepsis patients in the ICU. Similarly, in non-ICU
      settings, only 1 study that included patients with bacterial pneumonia reported
      outcomes after implementing an intervention consisting of early mobilization.
      These findings suggest that scant data regarding the efficacy of early
      mobilization following severe sepsis exist. Because hospitalists often care for
      this patient population, an opportunity for research in this area exists.

PMID- 25393648
TI  - Activation of HIV transcription with short-course vorinostat in HIV-infected
      patients on suppressive antiretroviral therapy.
AB  - Human immunodeficiency virus (HIV) persistence in latently infected resting
      memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone
      deacetylases (HDACs) are important in maintaining HIV latency and histone
      deacetylase inhibitors (HDACi) may reverse latency by activating HIV
      transcription from latently infected CD4+ T-cells. We performed a single arm,
      open label, proof-of-concept study in which vorinostat, a pan-HDACi, was
      administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals
      on suppressive antiretroviral therapy (ART). The primary endpoint was change in
      cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day
      14. The study is registered at ClinicalTrials.gov (NCT01365065). Vorinostat was
      safe and well tolerated and there were no dose modifications or study drug
      discontinuations. CA-US HIV RNA in blood increased significantly in 18/20
      patients (90%) with a median fold change from baseline to peak value of 7.4 (IQR
      3.4, 9.1). CA-US RNA was significantly elevated 8 hours post drug and remained
      elevated 70 days after last dose. Significant early changes in expression of
      genes associated with chromatin remodeling and activation of HIV transcription
      correlated with the magnitude of increased CA-US HIV RNA. There were no
      statistically significant changes in plasma HIV RNA, concentration of HIV DNA,
      integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation.
      Vorinostat induced a significant and sustained increase in HIV transcription from
      latency in the majority of HIV-infected patients. However, additional
      interventions will be needed to efficiently induce virus production and
      ultimately eliminate latently infected cells. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01365065.

PMID- 25393651
TI  - Mutations in the plant-conserved MTERF9 alter chloroplast gene expression,
      development and tolerance to abiotic stress in Arabidopsis thaliana.
AB  - The control of organelle gene expression in plants is far from fully understood.
      The characterization of mutants in Arabidopsis thaliana is assigning an
      increasingly prominent role to the mitochondrial transcription termination
      factors (mTERFs) in this process. To gain insight into the function of mTERF
      genes in plants, we took a reverse genetics approach to identify and characterize
      A. thaliana mTERF-defective mutants. Here we report the characterization of the
      mterf9 mutant, affected in an mTERF protein functionally conserved in plants and
      targeted to chloroplasts. Loss of MTERF9 results in defective chloroplast
      development, which is likely to cause paleness, stunted growth and reduced
      mesophyll cell numbers. Expression analysis of different plastid genes revealed
      reduced levels of plastid-encoded polymerase (PEP)-dependent transcripts and
      increased levels of transcripts dependent of nucleus-encoded polymerase. mterf9
      plants exhibited altered responses to sugars, abscisic acid (ABA), salt and
      osmotic stresses, and the microarray data analysis showed modifications in MTERF9
      expression after salt or mannitol treatments. Our genetic interactions results
      indicate a functional relationship between MTERF9 and the previously
      characterized MDA1 gene, and between MDA1 and some plastid ribosomal genes. MDA1
      and MTERF9 were upregulated in the mterf9 and mda1 mutants, respectively.
      Moreover, 21 of 50 genes were commonly co-expressed with MDA1 and MTERF9. The
      analysis of the MDA1 and MTERF9 promoters showed that both were rich in stress
      related cis-regulatory elements. Our results highlight the role of the MTERF9
      gene in plant biology and deepens the understanding of the functional
      relationship of plant mTERF genes. 

PMID- 25393652
TI  - Self-reported sleep lengths >= 9 hours among Swedish patients with stress-related
      exhaustion: Associations with depression, quality of sleep and levels of fatigue.
AB  - BACKGROUND: Insomnia-type sleep disturbances are frequent among patients
      suffering from stress-related exhaustion disorder. However, clinical observations
      indicate that a subgroup suffer from sleep lengths frequently exceeding 9 hours,
      coupled with great daytime sleepiness. AIMS: The aim of the present study was to
      investigate differences in socio-demographic variables, use of medications, sleep
      parameters, anxiety, depression and fatigue, between individuals with varying
      sleep lengths, in a sample of 420 Swedish patients (mean age 42 +/- 9 years; 77%
      women) referred to treatment for exhaustion disorder. Patients were allocated to
      the groups: "never/seldom >= 9 hours" (n = 248), "sometimes >= 9 hours" (n = 115)
      and "mostly/always >= 9 hours" (n = 57), based on their self-rated frequency of
      sleep lengths >= 9 hours. METHODS: The design was cross-sectional and data was
      collected by means of questionnaires at pre-treatment. RESULTS: Univariate
      analyses showed that patients in the "mostly/always >= 9 hours" group were more
      often on sick leave, and reported more depression and fatigue, better sleep
      quality and more daytime sleepiness, than patients in the other groups.
      Multivariate analyses showed that these patients scored higher on measures of
      fatigue than the rest of the sample independently of gender, use of
      antidepressants, sick leave, depression and quality of sleep. CONCLUSIONS:
      Patients suffering from exhaustion disorder and reporting excessive sleep seem to
      have a generally poorer clinical picture but better quality of sleep than their
      counterparts with shorter sleep lengths. The mechanisms underlying these
      differences, together with their prognostic value and implications for treatment
      remain to be elucidated in future studies.

PMID- 25393653
TI  - Validation of the work behavior inventory.
AB  - BACKGROUND: The Work Behavior Inventory (WBI) was developed in the USA for the
      assessment of vocational functioning for people with severe mental illness. It is
      rated in a work setting by an employment specialist through observation and an
      interview with the immediate supervisor. AIMS: The present study aims to examine
      the psychometric properties of the Norwegian version of the WBI. METHODS: The
      participants (n = 148) of the Job Management Program (JUMP) study for psychotic
      disorders were assessed with the WBI around the fourth week of work. A principal
      component analysis identified three substantial factors. RESULTS: The three
      corresponding scales were termed Social Skills revised, Work Quality revised and
      Compliance with work norms. The scales had a high internal consistency.
      Correlations with the Social Functioning Scale, education and previous work
      history supported the validity of the subscales. CONCLUSION: The results indicate
      that the Norwegian version of the WBI maintains good psychometric properties, and
      that vocational functioning can be reliably and validly assessed in a Norwegian
      setting. CLINICAL IMPLICATIONS: There has been a lack of validated assessment
      tools for this group in Norway. Functional assessment with the WBI provides a
      comprehensive evaluation of the individuals' strengths and challenges in the
      vocational setting, and provides goals for the vocational rehabilitation.

PMID- 25393654
TI  - Digital breast tomosynthesis: computer-aided detection of clustered
      microcalcifications on planar projection images.
AB  - This paper describes a new approach to detect microcalcification clusters (MCs)
      in digital breast tomosynthesis (DBT) via its planar projection (PPJ) image. With
      IRB approval, two-view (cranio-caudal and mediolateral oblique views) DBTs of
      human subject breasts were obtained with a GE GEN2 prototype DBT system that
      acquires 21 projection angles spanning 60 degrees  in 3 degrees  increments. A
      data set of 307 volumes (154 human subjects) was divided by case into independent
      training (127 with MCs) and test sets (104 with MCs and 76 free of MCs). A
      simultaneous algebraic reconstruction technique with multiscale bilateral
      filtering (MSBF) regularization was used to enhance microcalcifications and
      suppress noise. During the MSBF regularized reconstruction, the DBT volume was
      separated into high frequency (HF) and low frequency components representing
      microcalcifications and larger structures. At the final iteration, maximum
      intensity projection was applied to the regularized HF volume to generate a PPJ
      image that contained MCs with increased contrast-to-noise ratio (CNR) and reduced
      search space. High CNR objects in the PPJ image were extracted and labeled as
      microcalcification candidates. Convolution neural network trained to recognize
      the image pattern of microcalcifications was used to classify the candidates into
      true calcifications and tissue structures and artifacts. The remaining
      microcalcification candidates were grouped into MCs by dynamic conditional
      clustering based on adaptive CNR threshold and radial distance criteria. False
      positive (FP) clusters were further reduced using the number of candidates in a
      cluster, CNR and size of microcalcification candidates. At 85% sensitivity an FP
      rate of 0.71 and 0.54 was achieved for view- and case-based sensitivity,
      respectively, compared to 2.16 and 0.85 achieved in DBT. The improvement was
      significant (p-value = 0.003) by JAFROC analysis.

PMID- 25393655
TI  - Quantitative CT measurements of small pulmonary vessels in chronic obstructive
      pulmonary disease: do they change on follow-up scans?
AB  - The aims of this study were to perform a longitudinal evaluation of the cross
      sectional area (CSA) of small pulmonary vessels and the extent of emphysema
      measured on computed tomography (CT) scans of patients with chronic obstructive
      pulmonary disease (COPD), and to correlate the pulmonary vascular measurements
      with extent of emphysema. The institutional review board approved this
      retrospective study and waived the need for patients' informed consent. Seventy
      four patients with COPD who underwent both initial and follow-up CT scans at an
      interval of >=12 months were analysed. The CSA of small pulmonary vessels <5
      mm(2) was measured, and the percentage of total CSA of the area of the lung
      (%CSA<5 ) was calculated. The extent of emphysema was assessed as the percentage
      of low attenuation area (%LAA, <-950 Hounsfield units). Comparisons between
      initial and follow-up measurements were performed using the Wilcoxon signed-rank
      test. The relationship between longitudinal changes in %CSA<5 and %LAA during the
      follow-up period was assessed using the Spearman rank correlation. The %LAA
      increased significantly on follow-up CT scans (P<0.0001). The %CSA<5 was slightly
      decreased on follow-up scans, but the difference was not significant. Although
      longitudinal change in %LAA was positively correlated with duration of follow-up
      period (rho = 0.505, P<0.0001), longitudinal change in %CSA<5 was not. In
      conclusion, there was a progressive increase in the extent of emphysema over
      time, but no significant decrease in the CSA of small pulmonary vessels over the
      same time period.

PMID- 25393656
TI  - A low postoperative nonstimulated serum thyroglobulin level excludes the presence
      of persistent disease in low-risk papillary thyroid cancer patients: implication
      for radioiodine indication.
AB  - OBJECTIVE: To evaluate the presence of persistent disease, including on post
      therapy whole-body scan (RxWBS), in low-risk patients with papillary thyroid
      carcinoma (PTC) >1 cm who have low nonstimulated thyroglobulin (Tg) (measured
      with a sensitive assay), negative anti-Tg antibodies (TgAb) and neck ultrasound
      (US) showing no metastases after total thyroidectomy. PATIENTS: We studied 154
      patients with PTC >1 cm classified as low risk, who had US without metastases,
      negative TgAb, nonstimulated Tg <= 0.25 ng/ml and TSH <= 2 mIU/l about 3 months
      after total thyroidectomy. RESULTS: Tg measured immediately before (131) I was <=
      1 ng/ml in 89.5% of the patients and >1 ng/ml in 10.5%. None of the patients
      showed ectopic uptake on RxWBS. Uptake in the thyroid bed was observed in 146
      (94.8%) patients and was <= 2% in all of them. In the control assessment 9-12
      months after ablation, stimulated Tg (sTg) <= 1 ng/ml was achieved in 150
      patients (97.4%). Only one patient had sTg >2 ng/ml (2.5 ng/ml) and none of the
      patients had apparent disease detected by imaging methods. During further short
      term follow-up after control assessment (median of 24 months), none of the
      patients had tumour recurrence. CONCLUSIONS: The combination of nonstimulated Tg
      <=0.25 ng/ml, negative TgAb and US without metastases after thyroidectomy rules
      out the presence of persistent disease (including on RxWBS) in low-risk patients
      with PTC >1 cm. This demonstration weakens the indication of ablation with (131)
      I in these cases.

PMID- 25393657
TI  - Tumors of the pediatric maxillofacial skeleton: a 20-year clinical study.
AB  - IMPORTANCE: Pediatric jaw tumors are a rare clinical entity and are not well
      addressed in the otolaryngology literature. It is important that
      otolaryngologists be familiar with the clinical features, management, and
      outcomes associated with these lesions. OBJECTIVE: To review the clinical
      presentation, management, and outcomes of jaw tumors in children treated at a
      tertiary care academic center. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      medical record review of children 16 years or younger who presented to the
      departments of Oral-Maxillofacial Surgery and Otorhinolaryngology at the
      University of Maryland Medical Center between 1992 and 2012 and were diagnosed as
      having a jaw tumor. A PubMed review of literature from 1992 to 2013 on jaw tumors
      in children was also conducted. MAIN OUTCOMES AND MEASURES: Medical records were
      reviewed for data on symptoms, physical findings, pathologic diagnosis,
      intervention, and outcomes. RESULTS: The medical records of 76 patients evaluated
      for a jaw mass were reviewed, and 20 were found to have a diagnosis of a jaw
      tumor. The 2 most common pathologic diagnoses were ameloblastoma (n = 5) and
      juvenile ossifying fibroma (n = 4). Two tumors were malignant, a rhabdomyosarcoma
      and a teratoma. Thirteen patients presented with evidence of a mass or swelling,
      5 patients were asymptomatic with a lesion found on surveillance panoramic
      radiography, and 1 patient presented with epistaxis and 1 with facial weakness
      and pain. All tumors excluding a lymphangioma and a rhabdomyosarcoma were managed
      surgically. Eight patients underwent more than 1 procedure including secondary
      reconstruction prior to a satisfactory outcome. CONCLUSIONS AND RELEVANCE:
      Pediatric jaw tumors are rare lesions most commonly presenting with a swelling or
      mass. Patients can be asymptomatic with the lesion identified on routine imaging.
      Certain clinical features such as age, location of tumor, and presence or absence
      of bone and soft tissue can narrow the differential diagnosis and identify tumors
      that may be malignant. Incisional biopsy is an important first step. A majority
      of jaw tumors are benign but require surgical intervention for eradication of
      disease. Multiple procedures, including reconstruction, may be required for
      certain lesions prior to cure.

PMID- 25393658
TI  - Autosomal dominant hearing loss resulting from p.R75Q mutation in the GJB2 gene:
      nonsyndromic presentation in a South Indian family.
AB  - Mutations in the GJB2 gene encoding the gap junction protein Connexin 26 have
      been associated with autosomal recessive as well as dominant nonsyndromic hearing
      loss. Owing to the involvement of connexins in skin homeostasis, GJB2 mutations
      have also been associated with syndromic forms of hearing loss showing various
      skin manifestations. We report an assortatively mating hearing impaired family of
      south Indian origin with three affected members spread over two generations,
      having p.R75Q mutation in the GJB2 gene in the heterozygous condition. The
      inheritance pattern was autosomal dominant with mother and son being affected.
      Dermatological and histopathologic examinations showed absence of palmoplantar
      keratoderma. To the best of our knowledge, this is the first report from India on
      p.R75Q mutation in the GJB2 gene with nonsyndromic hearing loss. 

PMID- 25393661
TI  - Evolution of all-or-none strategies in repeated public goods dilemmas.
AB  - Many problems of cooperation involve repeated interactions among the same groups
      of individuals. When collective action is at stake, groups often engage in Public
      Goods Games (PGG), where individuals contribute (or not) to a common pool,
      subsequently sharing the resources. Such scenarios of repeated group interactions
      materialize situations in which direct reciprocation to groups may be at work.
      Here we study direct group reciprocity considering the complete set of reactive
      strategies, where individuals behave conditionally on what they observed in the
      previous round. We study both analytically and by computer simulations the
      evolutionary dynamics encompassing this extensive strategy space, witnessing the
      emergence of a surprisingly simple strategy that we call All-Or-None (AoN). AoN
      consists in cooperating only after a round of unanimous group behavior
      (cooperation or defection), and proves robust in the presence of errors, thus
      fostering cooperation in a wide range of group sizes. The principles encapsulated
      in this strategy share a level of complexity reminiscent of that found already in
      2-person games under direct and indirect reciprocity, reducing, in fact, to the
      well-known Win-Stay-Lose-Shift strategy in the limit of the repeated 2-person
      Prisoner's Dilemma. 

PMID- 25393664
TI  - A response to the New England Journal of Medicine article: a randomized trial of
      epidural glucocorticoid injections for spinal stenosis.

PMID- 25393660
TI  - Increased adult hippocampal neurogenesis is not necessary for wheel running to
      abolish conditioned place preference for cocaine in mice.
AB  - Recent evidence suggests that wheel running can abolish conditioned place
      preference (CPP) for cocaine in mice. Running significantly increases the number
      of new neurons in the hippocampus, and new neurons have been hypothesised to
      enhance plasticity and behavioral flexibility. Therefore, we tested the
      hypothesis that increased neurogenesis was necessary for exercise to abolish
      cocaine CPP. Male nestin-thymidine kinase transgenic mice were conditioned with
      cocaine, and then housed with or without running wheels for 32 days. Half of the
      mice were fed chow containing valganciclovir to induce apoptosis in newly divided
      neurons, and the other half were fed standard chow. For the first 10 days, mice
      received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. On
      the last 4 days, mice were tested for CPP, and then euthanized for measurement of
      adult hippocampal neurogenesis by counting the number of BrdU-positive neurons in
      the dentate gyrus. Levels of running were similar in mice fed valganciclovir
      containing chow and normal chow. Valganciclovir significantly reduced the numbers
      of neurons (BrdU-positive/NeuN-positive) in the dentate gyrus of both sedentary
      mice and runner mice. Valganciclovir-fed runner mice showed similar levels of
      neurogenesis as sedentary, normal-fed controls. However, valganciclovir-fed
      runner mice showed the same abolishment of CPP as runner mice with intact
      neurogenesis. The results demonstrate that elevated adult hippocampal
      neurogenesis resulting from running is not necessary for running to abolish
      cocaine CPP in mice.

PMID- 25393665
TI  - Variation in the management of thoracolumbar trauma and postoperative infection.
AB  - STUDY DESIGN: Multinational survey of spine trauma surgeons. OBJECTIVES: To
      survey spine trauma surgeons, examine the variety of management practices for
      thoracolumbar fractures, and investigate the need for future areas of study.
      BACKGROUND: Attempts to develop a universal thoracolumbar classification system
      represent the first step in standardizing treatment of thoracolumbar injuries,
      but there is little consensus regarding diagnosis and management of these
      injuries. METHODS: A survey questionnaire regarding a fictional neurologically
      intact patient with a burst fracture was administered to 46 spine surgeons. The
      questionnaire consisted of 2 domains: management of thoracolumbar fractures and
      management of postoperative infection. Survey results were compiled and evaluated
      and consensus arbitrarily assumed when the majority of surgeons agreed on a
      single question answer. RESULTS: Although majority consensus was reached on most
      questions, the interobserver reliability was poor. Consensus was achieved that
      magnetic resonance imaging should be performed during initial imaging. The
      majority would also operate regardless of magnetic resonance imaging findings,
      and would not operate at night. The favored technique was a posterior approach
      with decompression. Percutaneous fusion was considered a viable option by the
      majority of surgeons. No consensus was reached regarding instrumentation levels
      or construct length. The majority would use posterolateral bone grafting, and
      would not remove instrumentation nor perform an anterior reconstruction.
      Consensus was reached that postoperative bracing is unnecessary. Regarding
      management of infection, consensus was reached to use intraoperative vancomycin
      powder but not culture the nares before surgery. The majority used a set time
      period for antibiotic treatment when a drain was required, and would not apply
      supplementary bone graft at the time of final debridement and closure.
      CONCLUSIONS: There is lack of consensus regarding the appropriate management of
      thoracolumbar fractures. In the future, multicenter prospective studies are
      necessary to establish guidelines for the management of thoracolumbar fractures.

PMID- 25393667
TI  - How accurately can tokuhashi score system predict survival in the current
      practice for spinal metastases?: prospective analysis of 145 consecutive patients
      between 2007 and 2013.
AB  - STUDY DESIGN: Prospective observational study. SUMMARY OF BACKGROUND DATA:
      Tokuhashi score (TS) system was developed in 1990s and widely used for the
      prediction of survival in patients with spinal metastases. There were no reports
      about how accurately TS system predicts survival in the current practice.
      OBJECTIVE: To validate the accuracy of TS system using a recent series of the
      patients with metastatic spinal tumors, focusing on the primary tumor type.
      METHODS: Between January 2007 and March 2013, 145 patients who underwent surgical
      treatment for metastatic spinal tumors were followed up prospectively. The
      subjects were divided into 3 prognosis group according to TS system. The actual
      and predicted survivals were compared with calculate the accuracy rate. RESULTS:
      The mean age was 60.0 years. There were 96 male and 49 female patients. There are
      106 patients in poor prognosis group (A), 30 in intermediate prognosis group (B),
      and 9 in good prognosis group (C). The overall accuracy to predict the survival
      time was 57.2%. The accuracy rate was especially poor in breast cancer (44.4%)
      and rectal cancer (42.9%). Forty-three patients (40.6%) in group A and 9 patients
      (30.0%) in group B survived longer than predicted. The mean survival time was
      8.5, 18.1, and 41.6 months for group A, B, and C, respectively. Patients with
      rectal cancer showed poor survival profile than expected. CONCLUSIONS: The
      accuracy of TS system was suboptimal (57.2%). The predicted survival time needs
      to be increased in response to the recent population's data. The score given to
      the rectal cancer subgroup should be lowered.

PMID- 25393668
TI  - The association between cervical spine pathology and rotator cuff dysfunction.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the
      relationship between cervical spine (C-spine) and rotator cuff (RTC) pathology.
      SUMMARY OF BACKGROUND DATA: Cervical spine and RTC pathology cause significant
      shoulder pain in isolation and in tandem, but there is limited information about
      the relationship between these 2 entities. METHODS: Patients with a diagnosis of
      C-spine and/or RTC pathology between 2005 and 2011 were identified using a large
      national database composed of private payer as well as Medicare patient records.
      Patients with concomitant C-spine and RTC diagnoses were then stratified by age
      group and sex. Patients with lumbar spine (L-spine) and RTC pathology were used
      as a comparative group, and multivariate logistic regression was used for
      statistical analysis. RESULTS: Concomitant C-spine and RTC diagnoses were
      identified in 86,928 patients representing 13% of 679,112 patients with a RTC
      diagnosis and 16% of 531,177 patients with a C-spine diagnosis. The association
      between C-spine and RTC pathology increased significantly with age as RTC
      diagnoses were present in 13% of patients with C-spine pathology younger than 60
      years old but increased to 25% in C-spine patients older than 60 years
      (P<0.0001). For patients over 60 years old who developed a new C-spine diagnosis,
      11% would develop a new RTC diagnosis or undergo an operation for a RTC disorder
      within 5 years. Lumbar diagnosis codes (2,297,480 patients) were over 4 times
      more common than C-spine codes but RTC pathology had a significantly higher
      correlation with C-spine pathology than L-spine pathology (odds ratio, 2.32) and
      patients with C-spine pathology were more likely to develop new rotator cuff
      pathology (odds ratio, 1.53). CONCLUSIONS: The association between cervical spine
      and RTC pathology is significantly greater than that between L-spine and RTC
      pathology and increases substantially with patient age. Further studies are
      needed to elucidate the cause of this relationship.

PMID- 25393669
TI  - An outbreak of multiple serotypes of salmonella in New Zealand linked to
      consumption of contaminated tahini imported from Turkey.
AB  - A widespread salmonellosis outbreak linked to consumption of hummus made from
      contaminated tahini imported from Turkey occurred in New Zealand in November
      2012. This article summarizes the outbreak detection, investigation, and control.
      The New Zealand Enteric Reference Laboratory alerted public health units
      regarding a cluster of 11 persons with Salmonella Montevideo infection identified
      from different regions of the North Island of New Zealand. A multiagency outbreak
      investigation commenced to determine the source of illness and prevent further
      transmission. Salmonellosis is a notifiable disease in New Zealand. Outbreak
      cases were identified through routine salmonellosis notifications, and
      interviewed using a standardized questionnaire to identify common exposures.
      Clinical and food isolates were initially characterized by serotyping and then
      further typed by pulsed-field gel electrophoresis (PFGE). PFGE profiles were sent
      to PulseNet and international alerts were posted. The scope of the investigation
      widened to include persons with either Salmonella Maastricht and Salmonella
      Mbandaka infection following detection of these serotypes in tahini
      epidemiologically linked to laboratory-confirmed cases. All three of the tahini
      associated serotypes were detected in people who had consumed tahini, and these
      were found to have PFGE profiles indistinguishable from the tahini isolates.
      Twenty-seven salmonellosis cases infected with at least one of the three tahini
      associated Salmonella serotypes were detected between September 1 and December
      31, 2012; of these, 16 (59%) cases (12 with Salmonella Montevideo, 3 with
      Salmonella Mbandaka, and 1 with Salmonella Maastricht infection) had PFGE
      patterns indistinguishable from the outbreak profile. The investigation led to a
      trade withdrawal and consumer recall for tahini sesame paste from the consignment
      and products containing this tahini. The outbreak ceased following the recall.
      The importer of the implicated tahini was reminded of his duties as a food
      importer, including ensuring appropriate product testing. Changes to New Zealand
      legislation strengthened food safety responsibilities of food importers.

PMID- 25393670
TI  - Radiation resistance and injury in starved Escherichia coli O157:H7 treated with
      electron-beam irradiation in 0.85% saline and in apple juice.
AB  - This study evaluated the influence of starvation on the radiation resistance and
      injury in Escherichia coli O157:H7, following electron beam irradiation in 0.85%
      (wt/vol) saline and in apple juice. Washed exponential-phase cells of E. coli
      O157:H7 that were grown in tryptic soy broth (TSB) at 35 degrees C were starved
      in 0.85% saline (25 degrees C) for 10 days. Exponential- or stationary-phase
      cells grown in TSB (35 degrees C) served as controls. Samples of 0.85% saline or
      pasteurized apple juice, inoculated with control cells or cells starved for 8
      days, were exposed to electron beam irradiation at doses ranging from 0.0
      (control) to 0.70 kGy. The E. coli survivors were enumerated by plating diluted
      samples on tryptic soy agar or on Sorbitol McConkey agar and counting bacterial
      colonies after incubation (35 degrees C) for 24 h. Starved cells consistently
      exhibited higher irradiation D-values than controls (p<0.05). The D-values for
      control and starved E. coli O157:H7 in 0.85% saline were 0.11 and 0.26 kGy,
      respectively; D-values in apple juice were 0.16, 0.19, and 0.33 kGy for
      exponential, stationary, and starved cells, respectively. Irradiation (0.70 kGy)
      of E. coli O157:H7 in apple juice reduced numbers of exponential- and stationary
      phase cells by ~4.32 and 3.74 logs, respectively, whereas starved cells were
      reduced by only 2.20 logs. Exponential-phase cells exhibited the lowest
      resistance to irradiation, and sublethal injury in survivors of this group was
      higher than that of stationary-phase or starved cells irradiated at 0.50 or 0.70
      kGy (p<0.05). The results of this study indicate that starvation-induced stress
      cross-protects E. coli O157:H7 from ionizing radiation and should be considered
      an important factor when determining irradiation D-values for this pathogen.

PMID- 25393671
TI  - Study of the antibacterial activity in the gas phase of a chemical formulation
      for household waste management.
AB  - The aim of this study was to formulate a product (microbicide mixture) that could
      slow down the bacterial proliferation during the storage of household waste. We
      used harmless and natural components, known for their antimicrobial properties,
      in the liquid phase at direct contact with the microbes. The antimicrobial
      activity of the microbicide mixture formulated was evaluated over a range of
      concentration in two types of tests, in the liquid and in the gas phase. Once the
      efficacy of antimicrobial agent in the liquid phase in direct contact with the
      microbe (Escherichia coli) was confirmed, we adopted a new approach to evaluate
      the effect of the vapour phase both on the microbes' growth and on its duration.
      Here, we show that the perfect combination that gives rise to an antimicrobial
      mixture useful to control microbial growth (Staphylococcus aureus, Escherichia
      coli, Debaryomyces hansenii or Penicillium citrinum) up to 4 weeks is the one
      between more volatile agents (2-propanol and limonene) and a less volatile agent
      (cinnamaldehyde). The pleasant smell as well as the synergic antibacterial and
      antifungal function of the natural components of this mixture makes it attractive
      in domestic waste management. SIGNIFICANCE AND IMPACT OF THE STUDY: The novelty
      of this work is two-fold: on the one hand, to test various antimicrobial
      components of different volatility in a single microbicide mixture, and on the
      other, to study antimicrobial activity in the gas phase, other than the liquid
      phase. While previous authors tested the components individually as antimicrobial
      agents in the liquid phase at direct contact with the microbes, we tested them
      altogether as a mixture both in the liquid and in gas phase. The aim of this
      study was to disinfect small environments, such as garbage containers, by
      favouring the diffusion of the vapour phase to avoid the growth of microbes. This
      study proposes a new approach in the management and storage of household waste by
      inhibiting bacterial proliferation in the garbage can.

PMID- 25393672
TI  - NMR metabolomic analysis of exhaled breath condensate of asthmatic patients at
      two different temperatures.
AB  - Exhaled breath condensate (EBC) collection is a noninvasive method to investigate
      lung diseases. EBC is usually collected with commercial/custom-made condensers,
      but the optimal condensing temperature is often unknown. As such, the physical
      and chemical properties of exhaled metabolites should be considered when setting
      the temperature, therefore requiring validation and standardization of the
      collecting procedure. EBC is frequently used in nuclear magnetic resonance (NMR)
      based metabolomics, which unambiguously recognizes different pulmonary
      pathological states. Here we applied NMR-based metabolomics to asthmatic and
      healthy EBC samples collected with two commercial condensers operating at -27.3
      and -4.8  degrees C. Thirty-five mild asthmatic patients and 35 healthy subjects
      were included in the study, while blind validation was obtained from 20 asthmatic
      and 20 healthy different subjects not included in the primary analysis. We
      initially analyzed the samples separately and assessed the within-day, between
      day, and technical repeatabilities. Next, samples were interchanged, and,
      finally, all samples were analyzed together, disregarding the condensing
      temperature. Partial least-squares discriminant analysis of NMR spectra correctly
      classified samples, without any influence from the temperature. Input variables
      were either integral bucket areas (spectral bucketing) or metabolite
      concentrations (targeted profiling). We always obtained strong regression models
      (95%), with high average-quality parameters for spectral profiling (R(2) = 0.84
      and Q(2) = 0.78) and targeted profiling (R(2) = 0.91 and Q(2) = 0.87). In
      particular, although targeted profiling clustering is better than spectral
      profiling, all models reproduced the relative metabolite variations responsible
      for class differentiation. This warrants that cross comparisons are reliable and
      that NMR-based metabolomics could attenuate some specific problems linked to
      standardization of EBC collection. 

PMID- 25393673
TI  - Putting radiotherapy into orbit.

PMID- 25393674
TI  - Structural genomic alterations in primary mediastinal large B-cell lymphoma.
AB  - Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive non-Hodgkin
      lymphoma that displays phenotypic and genotypic similarity to Hodgkin lymphoma
      and diffuse large B-cell lymphoma. Studies using genome-wide discovery tools have
      revealed specific, recurrent structural aberrations as critical somatic events in
      the pathogenesis of PMBCL. These structural alterations prominently include
      transcript and protein altering rearrangements and copy number variations of the
      programmed death ligands 1 (CD274) and 2 (PDCD1LG2), CIITA, JAK2 and REL.
      Importantly, evidence is emerging that these acquired structural genomic changes,
      in synergy with other somatic alterations, contribute to PMBCL pathogenesis by
      influencing tumor microenvironment interactions that favor malignant B-cell
      growth. The means by which these rearrangements arise are not well understood.
      However, analysis of breakpoint junctions at base-pair resolution provides
      preliminary insight into putative rearrangement mechanisms. As the field also
      anticipates predictive value and therapeutic targeting of structural changes
      involving programmed death ligands and JAK2, a review of therapies that will
      likely shape future lymphoma treatment is needed. 

PMID- 25393675
TI  - Treatment of elderly patients with acute myeloid leukemia adjusted for
      performance status and presence of comorbidities: a Polish Adult Leukemia Group
      study.
AB  - This prospective study estimated outcomes in 509 elderly patients with acute
      myeloid leukemia (AML) with different treatment approaches depending on Eastern
      Cooperative Oncology Group (ECOG) performance status and Charlson Comorbidity
      Index (CCI). Patients were stratified into fit (ECOG 0-2 and CCI 0-2) or frail
      (ECOG>2 and/or CCI>2) groups. Fit patients with CCI 0 received intensive
      chemotherapy whilst reduced-intensive chemotherapy (R-IC) was given to those with
      CCI 1-2. Frail patients received best supportive therapy. Fit patients presented
      a longer overall survival (OS) than frail subjects, but 8-week mortality rates
      were similar. The complete response (CR) rate between fit CCI 0 and CCI 1-2
      subgroups was significantly different. Both of the fit subgroups showed similar 8
      week mortality rates and OS probabilities. Allocating fit patients with CCI 1-2
      to R-IC enabled an increase in the group of elderly patients who could be treated
      with the intention of inducing remission.

PMID- 25393676
TI  - Gemtuzumab ozogamicin in combination with intensive chemotherapy in relapsed or
      refractory acute myeloid leukemia.
AB  - The prognosis of refractory/relapsed acute myeloid leukemia (AML) remains poor.
      The complete response (CR) rate after relapse is around 25%, with 11% of patients
      still alive after 5 years. The efficacy and toxicity of fractionated gemtuzumab
      ozogamicin (fGO; 3 mg/m2, days 1, 4, 7) in combination with intensive
      chemotherapy were retrospectively evaluated in patients with refractory/relapsed
      AML. Thirty-six patients (median age 54 years) were included. European
      LeukemiaNet classification was as follows: favorable (n=6), intermediate-I
      (n=13), intermediate-II (n=8), adverse (n=9). Median CR duration was 7.16 months
      (1.63-96.8). The overall response rate was 38.8%, with CR in eight patients
      (22.2%) and CR with incomplete platelet recovery (CRp) in six patients (16.7%).
      Two-year overall survival was 26% (95% confidence interval [CI]: 12-42) and 2
      year relapse free-survival was 18.5% (95% CI: 6.6-35.0). Salvage therapy with
      fractionated GO in patients with very high-risk disease produced a 38.8% response
      rate and may be considered as a bridge therapy to transplant.

PMID- 25393677
TI  - Ceramide participates in lysosome-mediated cell death induced by type II anti
      CD20 monoclonal antibodies.
AB  - Considering the variable and often modest therapeutic efficacy of rituximab for a
      substantial proportion of patients suffering from non-Hodgkin lymphomas (NHLs),
      various type II anti-CD20 monoclonal antibodies (mAbs) with excellent ability in
      inducing programmed cell death (PCD) are currently being developed for their
      enhanced therapeutic index. Although homotypic adhesion (HA) and lysosome leakage
      are proven to be of vital importance in type II mAb-induced PCD in NHL cells, the
      detailed relationship between them remains unclear. Herein, for the first time we
      discovered that improved intracellular ceramide level is an important mediator
      between HA and lysosome leakage in tositumomab-induced cell death. Further
      experimental results revealed that the generation of intracellular ceramide acts
      as the outcome of HA and major cause of lysosome leakage. The clarification of
      ceramide involvement in type II anti-CD20 mAb-induced PCD may provide new ideas
      on CD20-based immunotherapy against NHLs. 

PMID- 25393678
TI  - GPA: a statistical approach to prioritizing GWAS results by integrating
      pleiotropy and annotation.
AB  - Results from Genome-Wide Association Studies (GWAS) have shown that complex
      diseases are often affected by many genetic variants with small or moderate
      effects. Identifications of these risk variants remain a very challenging
      problem. There is a need to develop more powerful statistical methods to leverage
      available information to improve upon traditional approaches that focus on a
      single GWAS dataset without incorporating additional data. In this paper, we
      propose a novel statistical approach, GPA (Genetic analysis incorporating
      Pleiotropy and Annotation), to increase statistical power to identify risk
      variants through joint analysis of multiple GWAS data sets and annotation
      information because: (1) accumulating evidence suggests that different complex
      diseases share common risk bases, i.e., pleiotropy; and (2) functionally
      annotated variants have been consistently demonstrated to be enriched among GWAS
      hits. GPA can integrate multiple GWAS datasets and functional annotations to seek
      association signals, and it can also perform hypothesis testing to test the
      presence of pleiotropy and enrichment of functional annotation. Statistical
      inference of the model parameters and SNP ranking is achieved through an EM
      algorithm that can handle genome-wide markers efficiently. When we applied GPA to
      jointly analyze five psychiatric disorders with annotation information, not only
      did GPA identify many weak signals missed by the traditional single phenotype
      analysis, but it also revealed relationships in the genetic architecture of these
      disorders. Using our hypothesis testing framework, statistically significant
      pleiotropic effects were detected among these psychiatric disorders, and the
      markers annotated in the central nervous system genes and eQTLs from the Genotype
      Tissue Expression (GTEx) database were significantly enriched. We also applied
      GPA to a bladder cancer GWAS data set with the ENCODE DNase-seq data from 125
      cell lines. GPA was able to detect cell lines that are biologically more relevant
      to bladder cancer. The R implementation of GPA is currently available at
      http://dongjunchung.github.io/GPA/.

PMID- 25393680
TI  - Multiple-stimulus-responsive supramolecular gels of two components and dual
      chiroptical switches.
AB  - A new class of L-glutamic gelators, LG12(CH2)nCOOH, containing different lengths
      of methylene spacer were synthesized. It was found that the gelation ability of
      these compounds themselves was very weak. However, when another compound, p
      xylylenediamine (XEA), was introduced, the gelation ability was improved greatly.
      In particular, LG12(CH2)10COOH showed super-gelation ability in the presence of
      XEA, which could immobilize almost all of the solvents except methanol. Moreover,
      the formed supramolecular gels even could be molded. Interestingly, some
      supramolecular gels of LG12(CH2)nCOOH and XEA could respond to multiple stimuli,
      such as heating, shaking, sonication, and acid/base. The studies of CD spectra
      suggested that the supramolecular chirality induced by self-assembled chiral
      gelator molecules in gels could be tuned by the length of methylene spacer. In
      addition, the supramolecular chirality could be regulated as on/off by heating
      cooling or external NH3/HCl. This would facilitate the development of dual
      chiroptical switches by temperature and acid/base.

PMID- 25393679
TI  - Dihydroflavonol 4-reductase genes encode enzymes with contrasting substrate
      specificity and show divergent gene expression profiles in Fragaria species.
AB  - During fruit ripening, strawberries show distinct changes in the flavonoid
      classes that accumulate, switching from the formation of flavan 3-ols and
      flavonols in unripe fruits to the accumulation of anthocyanins in the ripe
      fruits. In the common garden strawberry (Fragaria*ananassa) this is accompanied
      by a distinct switch in the pattern of hydroxylation demonstrated by the almost
      exclusive accumulation of pelargonidin based pigments. In Fragaria vesca the
      proportion of anthocyanins showing one (pelargonidin) and two (cyanidin) hydroxyl
      groups within the B-ring is almost equal. We isolated two dihydroflavonol 4
      reductase (DFR) cDNA clones from strawberry fruits, which show 82% sequence
      similarity. The encoded enzymes revealed a high variability in substrate
      specificity. One enzyme variant did not accept DHK (with one hydroxyl group
      present in the B-ring), whereas the other strongly preferred DHK as a substrate.
      This appears to be an uncharacterized DFR variant with novel substrate
      specificity. Both DFRs were expressed in the receptacle and the achenes of both
      Fragaria species and the DFR2 expression profile showed a pronounced dependence
      on fruit development, whereas DFR1 expression remained relatively stable. There
      were, however, significant differences in their relative rates of expression. The
      DFR1/DFR2 expression ratio was much higher in the Fragaria*ananassa and enzyme
      preparations from F.*ananassa receptacles showed higher capability to convert DHK
      than preparations from F. vesca. Anthocyanin concentrations in the F.*ananassa
      cultivar were more than twofold higher and the cyanidin:pelargonidin ratio was
      only 0.05 compared to 0.51 in the F. vesca cultivar. The differences in the fruit
      colour of the two Fragaria species can be explained by the higher expression of
      DFR1 in F.*ananassa as compared to F. vesca, a higher enzyme efficiency (Kcat/Km
      values) of DFR1 combined with the loss of F3'H activity late in fruit development
      of F.*ananassa. 

PMID- 25393682
TI  - Overdominance interacts with linkage to determine the rate of adaptation to a new
      optimum.
AB  - Overdominance, or a fitness advantage of a heterozygote over both homozygotes,
      can occur commonly with adaptation to a new optimum phenotype. We model how such
      overdominant polymorphisms can reduce the evolvability of diploid populations,
      uncovering a novel form of epistatic constraint on adaptation. The fitness load
      caused by overdominant polymorphisms can most readily be ameliorated by evolution
      at tightly linked loci; therefore, traits controlled by multiple loosely linked
      loci are predicted to be strongly constrained. The degree of constraint is also
      sensitive to the shape of the relationship between phenotype and fitness, and the
      constraint caused by overdominance can be strong enough to overcome the effects
      of clonal interference on the rate of adaptation for a trait. These results point
      to novel influences on evolvability that are specific to diploids and interact
      with genetic architecture, and they predict a source of stochastic variability in
      eukaryotic evolution experiments or cases of rapid evolution in nature. 

PMID- 25393681
TI  - Excited state proton transfer of natural flavonoids and their chromophores in
      duplex and tetraplex DNAs.
AB  - Fisetin (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'
      pentahydroxyflavone) are the bioactive plant flavonoids that are potentially
      useful therapeutic drugs for the treatment of a broad spectrum of diseases,
      including atherosclerosis, cardiovascular disease, obesity, hypertension, and
      cancer. 3-Hydroxyflavone (3HF) and 7-hydroxyflavone (7HF) are the synthetic
      chromophores of fisetin and quercetin. We have exploited dual luminescence
      properties of fisetin and quercetin along with 3-HF and 7HF to examine their
      efficacy of binding and compare their interactions with DNA, which is one of the
      macromolecular targets of flavonoids in physiological systems. Following the
      sequence of the human telomeric DNA 5'-d (CCCTAA-)n/(-TTAGGG)n-5', two single
      stranded DNA oligonucleotides, 5'-d(C3TA2)3C3-3' and 5'-d(T2AG3)4-3', and their
      duplex were used as receptors to study binding by the ligands quercetin, fisetin,
      and their chromophores. Circular dichroism, differential absorption, UV thermal
      melting, and size exclusion chromatographic studies indicated the formation of
      unusual DNA structures (such as C4 and G4 tetraplexes) for both the C- and G-rich
      single-stranded DNAs. Upon binding to DNA, dramatic changes were observed in the
      intrinsic fluorescence behavior of the flavonoids. Molecular docking studies were
      performed to describe the likely binding sites for the ligands. The spectroscopic
      studies on flavonoid-DNA interactions described herein demonstrate a powerful
      approach for examining their DNA binding through exploiting the highly sensitive
      intrinsic fluorescence properties of the flavonoids as their own "reporter" for
      their interactions with macromolecular targets. 

PMID- 25393683
TI  - Charles Buys (1942-2014).

PMID- 25393685
TI  - A rotary molecular motor gated by electrical energy.
AB  - DFT calculations predict that the chiral pentiptycene derivative E-1 possesses
      distinct rotational potential energy surfaces in the neutral vs the radical
      anionic (E-1(*-)) form such that continued electrochemical switching between E-1
      and E-1(*-) could lead to a directional rotation of the pentiptycene rotor about
      the exocyclic C-C bond. The time scale of random Brownian rotation is ~10(6) s
      for E-1 and ~170 s for E-1(*-) at 150 K, and thus a switching time scale of 0.2 s
      could readily bias the rotation direction to >99% at 150 K. The synthetic
      feasibility, line-shape analysis on the VT (1)H NMR spectra, and electrochemical
      redox switching of E-1 are demonstrated. 

PMID- 25393686
TI  - Assessing anthracycline-treated childhood cancer survivors with advanced stress
      echocardiography.
AB  - BACKGROUND: Surveillance for anthracycline cardiotoxicity in cancer survivors
      typically utilizes resting M-mode and two-dimensional echocardiography, which are
      insensitive to detection of subtle myocardial changes. We examined childhood
      cancer survivors treated with anthracyclines during exercise using various
      echocardiography techniques to investigate if these tools can better detect
      subclinical cardiac dysfunction. PROCEDURE: We recruited asymptomatic survivors
      at least five years post treatment. Echocardiography was performed at rest and at
      termination of exercise utilizing tissue Doppler techniques and strain rate
      imaging. RESULTS: Eighty participants were characterized by cardiotoxicity risk
      status (high [12], moderate [23], low [24], no risk [21]) as defined by the
      Children's Oncology Group Long Term Follow-Up Guidelines v3.0. The high-risk
      group had a higher resting heart rate than controls (100 vs. 88 bpm [P for trend
      = 0.049]). Peak aerobic capacity in all groups was similar. Compared to controls
      at rest, the high-risk group had evidence of diastolic dysfunction with lower E/A
      ratios (1.4 vs. 2.0, P = 0.008) and higher septal early diastolic velocities
      (E/E') of 11.7 versus 9.9 (P = 0.165). With exercise, this difference resolved
      and myocardial contractile reserve was preserved. CONCLUSIONS: Asymptomatic,
      pediatric cancer survivors at high-risk for anthracycline cardiotoxicity have
      some evidence of diastolic filling abnormalities at rest. With exercise, they
      augment their systolic and diastolic function to achieve normal maximal aerobic
      capacity suggesting they are able to compensate for mild cardiac dysfunction in
      the early years after exposure. Additionally, findings suggest that routine
      exercise echocardiography may not be a useful surveillance tool to assess
      anthracycline cardiotoxicity.

PMID- 25393687
TI  - Comparative analysis of colorimetric staining in skin using open-source software.
AB  - Colorimetric staining techniques such as immunohistochemistry (IHC),
      immunofluorescence (IF) and histochemistry (HC) provide useful information
      regarding the localization and relative amount of a molecule/substance in skin.
      We have developed a novel, straightforward method to assess colorimetric staining
      by combining features from two open-source software programs. As a proof of
      principle, we demonstrate the utility of this approach by analysing changes in
      skin melanin deposition during the radiation-induced tanning response of Yucatan
      mini-pigs. This method includes a visualization step to validate the accuracy of
      colour selection before quantitation to ensure accuracy. The data show that this
      method is robust and will provide a means to obtain accurate comparative analyses
      of staining in IHC/IF/HC samples. 

PMID- 25393689
TI  - Quality of vegetable oil prior to fortification is an important criteria to
      achieve a health impact.
AB  - Unbranded palm cooking oil has been fortified for several years and can be found
      in the market with different oxidation levels. This study aimed to investigate
      the stability and shelf life of unbranded, bulk, vitamin A-fortified palm oils
      with the most commonly observed oxidation levels in Indonesia. Three types of
      cooking oils were tested: (i) cooking oil with a peroxide value (PV) below 2 mEq
      O2/kg (PO1); (ii) cooking oil with a PV around 4 mEq O2/kg (PO2); and (iii)
      cooking oil with a PV around 9 mEq O2/kg (PO3). The oil shelf life was determined
      by using accelerated shelf life testing (ASLT), where the product was stored at
      60, 75 and 90  degrees C, and then PV, free fatty acid and vitamin A
      concentration in the oil samples were measured. The results showed that PO1 had a
      shelf life of between 2-3 months, while PO2's shelf life was a few weeks and
      PO3's only a few days. Even given those varying shelf lives, the vitamin A loss
      in the oils was still acceptable, at around 10%. However, the short shelf life of
      highly oxidized cooking oil, such as PO3, might negatively impact health, due to
      the potential increase of free radicals of the lipid peroxidation in the oil.
      Based on the results, the Indonesian government should prohibit the sale of
      highly-oxidized cooking oil. In addition, government authorities should promote
      and endorse the fortification of only cooking oil with low peroxide levels to
      ensure that fortification is not associated with any health issues associated
      with high oxidation levels of the cooking oil. 

PMID- 25393690
TI  - Current controversies in prenatal diagnosis 1: NIPT for chromosome abnormalities
      should be offered to women with low a priori risk.
AB  - In its successful annual cycle of controversies and debates, the International
      Society of Prenatal Diagnosis and Therapy once again addressed non-invasive
      prenatal testing (NIPT) by following up on the 2013 controversy, 'Should non
      invasive DNA testing be the standard screening test for Down syndrome in all
      pregnant women'? with the proposition, 'NIPT for chromosomel abnormalities should
      be offered to women with low a priori risk'.

PMID- 25393688
TI  - Interactions between C-reactive protein genotypes with markers of nutritional
      status in relation to inflammation.
AB  - Inflammation, as indicated by C-reactive protein concentrations (CRP), is a risk
      factor for chronic diseases. Both genetic and environmental factors affect
      susceptibility to inflammation. As dietary interventions can influence
      inflammatory status, we hypothesized that dietary effects could be influenced by
      interactions with single nucleotide polymorphisms (SNPs) in the CRP gene. We
      determined 12 CRP SNPs, as well as various nutrition status markers in 2010 black
      South Africans and analyzed their effect on CRP. Interactions were observed for
      several genotypes with obesity in determining CRP. Lipid intake modulated the pro
      inflammatory effects of some SNPs, i.e., an increase in both saturated fatty acid
      and monounsaturated fatty acid intake in those homozygous for the polymorphic
      allele at rs2808630 was associated with a larger increase in CRP. Those harboring
      the minor alleles at rs3093058 and rs3093062 presented with significantly higher
      CRP in the presence of increased triglyceride or cholesterol intake. When
      harboring the minor allele of these SNPs, a high omega-6 to -3 ratio was,
      however, found to be anti-inflammatory. Carbohydrate intake also modulated CRP
      SNPs, as HbA1C and fasting glucose levels interacted with some SNPs to influence
      the CRP. This investigation highlights the impact that nutritional status can
      have on reducing the inherent genetic susceptibility to a heightened systemic
      inflammatory state. 

PMID- 25393691
TI  - Arsenic: bioaccessibility from seaweed and rice, dietary exposure calculations
      and risk assessment.
AB  - Arsenic is a metalloid that occurs in food and the environment in different
      chemical forms. Inorganic arsenic is classified as a class I carcinogen. The
      inorganic arsenic intake from food and drinking water varies depending on the
      geographic arsenic background. Non-dietary exposure to arsenic is likely to be of
      minor importance for the general population within the European Union. In Europe,
      arsenic in drinking water is on average low, but food products (e.g. rice and
      seaweed) are imported from all over the world including from regions with
      naturally high arsenic levels. Therefore, specific populations living in Europe
      could also have a high exposure to inorganic arsenic due to their consumption
      pattern. Current risk assessment is based on exposure via drinking water. For a
      good estimation of the risks of arsenic in food, it is important to investigate
      if the bioavailability of inorganic arsenic from food is different from drinking
      water. The present study further explores the issue of European dietary exposure
      to inorganic arsenic via rice and seaweed and its associated health risks. The
      bioavailability of inorganic arsenic was measured in in vitro digestion
      experiments. The data indicate that the bioavailability of inorganic arsenic is
      similar for rice and seaweed compared with drinking water. The calculated dietary
      intake for specific European Union populations varied between 0.44 and 4.51 ug kg
      1 bw day-1. The margins of exposure between the inorganic intake levels and the
      BMDL0.5 values as derived by JECFA are low. Decreasing the intake of inorganic
      arsenic via Hijiki seaweed could be achieved by setting legal limits similar to
      those set for rice by the Codex Alimentarius Commission in July 2014.

PMID- 25393692
TI  - Unicompartmental and bicompartmental knee osteoarthritis show different patterns
      of mononuclear cell infiltration and cytokine release in the affected joints.
AB  - It is still controversial which cell types are responsible for synovial
      inflammation in osteoarthritic (OA) joints. The aim of this study was to quantify
      the mononuclear cell populations and their cytokines in patients with different
      knee OA subtypes. Synovial membrane (SM), synovial fluid (SF) and peripheral
      blood (PB) were harvested from patients with unicompartmental (UC) and
      bicompartmental (BC) knee OA. Frequencies of mononuclear cells were assessed by
      flow cytometry in PB and SM. Naive SF samples were analysed for a broad variety
      of cytokines by multiplex analysis. SM of both groups displayed a distinct
      mononuclear cell infiltration, with CD14(+) macrophages being the major cell
      population, followed by CD4(+) T cells and only small numbers of CD8(+) T,
      CD19(+) B and CD16(+) CD56(+) natural killer (NK) cells. Between the two groups,
      SM of BC OA showed significantly higher amounts of mononuclear cells (135.7 +/-
      180 versus 805 +/- 675 cells/mg, P = 0.0009) and higher CD4(+) T cell presence
      (3.4 +/- 4.6 versus 9.1 +/- 7.5%, P = 0.0267). SF of BC OA displayed
      significantly higher concentrations for a number of proinflammatory cytokines
      [CXCL1, eotaxin, interferon (IFN)-gamma, interleukin (IL)-7, IL-8, IL-9, IL-12].
      UC and BC OA show significant differences in their synovial inflammatory pattern.
      Whereas in UC OA CD14(+) macrophages are the predominant cell population, BC OA
      has a higher inflammatory profile and seems to be driven by CD14(+) macrophages
      and CD4(+) T cells. Inclusion of clinical information into the analysis of
      cellular and molecular results is pivotal in understanding the pathophysiology of
      OA. 

PMID- 25393693
TI  - HER2 expression in fine needle aspirates of lymph nodes detected by preoperative
      axillary ultrasound in breast cancer patients.
AB  - The purpose of this study was to assess the usefulness of HER2 levels in
      ultrasonographically guided fine-needle aspiration biopsy (US-FNA) aspirates of
      axillary lymph nodes (ALNs) in the determination of lymph node metastasis or the
      characterization of primary breast cancer, and to correlate the HER2 levels in US
      FNA aspirates (FNA-HER2s) of metastatic ALNs with the HER2 statuses of
      corresponding primary breast cancers. An institutional review board approved the
      study. Between January and October 2010, 164 patients with 167 ALNs examined by
      US-FNA were included. FNA-HER2s of ALNs were measured by chemiluminescence
      immunoassay, and they were correlated with cytologic/final diagnoses. Receiver
      operating characteristics (ROC) curve analysis was performed to evaluate the
      diagnostic ability to differentiate benign and metastatic ALNs. Additionally, FNA
      HER2s of metastatic ALNs were correlated with HER2 status and other
      clinicopathologic variables of the primary breast cancers. Among the 167 ALNs,
      138 were metastatic and 29 were benign. The mean FNA-HER2 (6.3 ng/ml) of
      metastatic ALNs was higher than that of benign ALNs. All 29 benign ALNs showed no
      measurable value of FNA-HER2 (0.0 ng/ml). The area under the ROC curves of FNA
      HER2 of ALNs was 0.679 for the diagnosis of ALN metastasis. The FNA-HER2 statuses
      of 108 metastatic ALNs (79.4%) were concordant with the HER2 statuses of the
      corresponding primary breast cancers. In a subgroup analysis of HER2-positive
      cancers with ALN metastasis, distant metastasis was significantly associated with
      FNA-HER2-negativity of metastatic ALNs (P = 0.04). Although FNA-HER2 of ALNs did
      not improve the diagnostic performance of FNA cytology in preoperative diagnosis
      of ALN metastasis of overall patients, FNA-HER2-positive metastatic ALNs were
      significantly associated with HER2-positivity of primary breast cancers.
      Additionally, FNA-HER2 analysis of ALN may help to develop more personalized
      treatment protocol for breast cancer patients by determining the concordance or
      discordance of HER2 status between primary cancers and metastatic ALNs. 

PMID- 25393694
TI  - Dynamics and nature of support in the personal networks of people with type 2
      diabetes living in Europe: qualitative analysis of network properties.
AB  - BACKGROUND: Living with and self-managing a long-term condition implicates a
      diversity of networked relationships. This qualitative study examines the
      personal communities of support of people with type 2 diabetes. METHODS: We
      conducted 170 biographical interviews in six European countries (Bulgaria,
      Greece, the Netherlands, Norway, Spain and UK) to explore social support and
      networks. Analysis was framed with reference to three predetermined social
      support mechanisms: the negotiation of support enabling engagement with healthy
      practices, navigation to sources of support and collective efficacy. Each
      interview was summarized to describe navigation and negotiation of participants'
      networks and the degree of collective efficacy. RESULTS: Analysis highlighted the
      similarities and differences between countries and provided insights into
      capacities of networks to support self-management. The network support mechanisms
      were identified in all interviews, and losses and gains in networks impacted on
      diabetes management. There were contextual differences between countries, most
      notably the impact of financial austerity on network dynamics. Four types of
      network are suggested: generative, diverse and beneficial to individuals; proxy,
      network members undertook diabetes management work; avoidant, support not engaged
      with; and struggling, diabetes management a struggle or not prioritized.
      CONCLUSIONS: It is possible to differentiate types of network input to living
      with and managing diabetes. Recognizing the nature of active, generative aspects
      of networks support is likely to have relevance for self-management support
      interventions either through encouraging continuing development and maintenance
      of these contacts or intervening to address struggling networks through
      introducing the means to connect people to additional sources of support.

PMID- 25393695
TI  - The Rockefeller University Graduate Tracking Survey System.
AB  - BACKGROUND: It is essential to track the careers and accomplishments of the
      graduates of translational research training programs to assess the impact of the
      programs and to improve them. The major obstacle is the lack of a convenient
      method to collect the information in a comprehensive and standardized manner.
      METHODS: We have developed a Web-based electronic Graduate Tracking Survey System
      (GTSS) that prepopulates the graduate's information on publications, grants,
      patents, and clinical trials from public data sources, thus insuring a uniform
      data format, facilitating survey completion, and facilitating the aggregation of
      data at individual or multiple sites. GTSS questions are designed to assess
      whether trainees make important contributions that improve human health, and to
      track related "surrogate" career development indicators of likely future success.
      RESULTS: The GTSS has been in use at Rockefeller University since 2011 and has
      been adopted by 21 other Clinical and Translational Science Award programs.
      CONCLUSIONS: The GTSS provides an efficient and convenient mechanism to track the
      graduates of a wide variety of training programs. It has the potential to
      aggregate standardized data across institutions, thus providing benchmarks for
      the assessment of individual training programs and data for program improvement.

PMID- 25393697
TI  - Cherchez la femme.

PMID- 25393696
TI  - Coincident pre-diabetes is associated with dysregulated cytokine responses in
      pulmonary tuberculosis.
AB  - BACKGROUND: Cytokines play an important role in the pathogenesis of pulmonary
      tuberculosis (PTB)--Type 2 diabetes mellitus co-morbidity. However, the cytokine
      interactions that characterize PTB coincident with pre-diabetes (PDM) are not
      known. METHODS: To identify the influence of coincident PDM on cytokine levels in
      PTB, we examined circulating levels of a panel of cytokines in the plasma of
      individuals with TB-PDM and compared them with those without PDM (TB-NDM).
      RESULTS: TB-PDM is characterized by elevated circulating levels of Type 1
      (IFNgamma, TNFalpha and IL-2), Type 17 (IL-17A and IL-17F) and other pro
      inflammatory (IL-1beta, IFNbeta and GM-CSF) cytokines. TB-PDM is also
      characterized by increased systemic levels of Type 2 (IL-5) and regulatory (IL-10
      and TGFbeta) cytokines. Moreover, TB antigen stimulated whole blood also showed
      increased levels of pro-inflammatory (IFNgamma, TNFalpha and IL-1beta) cytokines
      as well. However, the cytokines did not exhibit any significant correlation with
      HbA1C levels or with bacterial burdens. CONCLUSION: Our data reveal that pre
      diabetes in PTB individuals is characterized by heightened cytokine
      responsiveness, indicating that a balanced pro and anti - inflammatory cytokine
      milieu is a feature of pre-diabetes--TB co-morbidity.

PMID- 25393698
TI  - Improvement of communication and interpersonal competence in telenursing-
      development of a self-assessment tool.
AB  - AIMS AND OBJECTIVES: The aim of this study was to develop a self-assessment tool
      aiming to raise telenurses' awareness of their communication and interpersonal
      competence, and highlight areas in need of improvement. BACKGROUND: Several
      studies have revealed the need for development of communication competence in
      telenursing. Structured analyses of conversations with patients/callers, is one
      way to increase telenurses' awareness of their unique communication and
      interpersonal competence. DESIGN: Instrument development, Validation assessment
      using the method Content Validity Index. METHOD: The process to determine content
      validity was done in two stages; the development stage and the assessment stage.
      The development stage started with a literature search. The assessment stage was
      separated into two phases, assessment by an expert group and assessment and test
      by telenurses. The telenurses also participated in consensus discussions.
      RESULTS: A telenursing self-assessment tool with 58 items was developed. The
      items were sorted into five sections according to the nursing process.
      CONCLUSION: This study describes the thorough development process of the
      telenursing self-assessment tool to be used by telenurses in order to become
      aware of their unique communication and interpersonal competence when analysing
      their own conversations with patients/callers. As a formative tool it is meant to
      provide self-direction, feedback and coaching, and create learning opportunities.
      RELEVANCE TO CLINICAL PRACTICE: The self-assessment tool helps the telenurse to
      follow the nursing process, to be patient-centred, and it is meant to provide
      self-direction, feedback, and coaching, as well as create learning opportunities.
      The tool can contribute to the development of communication and interpersonal
      competence in telephone advice nursing. Further development of the tool may
      provide an objective scoring instrument for evaluating communication training and
      education in the field.

PMID- 25393699
TI  - Comparison of the Full Outline of UnResponsiveness score and the Glasgow Coma
      Scale in predicting mortality in critically ill patients*.
AB  - OBJECTIVE: Impaired consciousness has been incorporated in prediction models that
      are used in the ICU. The Glasgow Coma Scale has value but is incomplete and
      cannot be assessed in intubated patients accurately. The Full Outline of
      UnResponsiveness score may be a better predictor of mortality in critically ill
      patients. SETTING: Thirteen ICUs at five U.S. hospitals. SUBJECTS: One thousand
      six hundred ninety-five consecutive unselected ICU admissions during a six-month
      period in 2012. DESIGN: Glasgow Coma Scale and Full Outline of UnResponsiveness
      score were recorded within 1 hour of admission. Baseline characteristics and
      physiologic components of the Acute Physiology and Chronic Health Evaluation
      system, as well as mortality were linked to Glasgow Coma Scale/Full Outline of
      UnResponsiveness score information. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: We recruited 1,695 critically ill patients, of which 1,645 with complete
      data could be linked to data in the Acute Physiology and Chronic Health
      Evaluation system. The area under the receiver operating characteristic curve of
      predicting ICU mortality using the Glasgow Coma Scale was 0.715 (95% CI, 0.663
      0.768) and using the Full Outline of UnResponsiveness score was 0.742 (95% CI,
      0.694-0.790), statistically different (p = 0.001). A similar but nonsignificant
      difference was found for predicting hospital mortality (p = 0.078). The
      respiratory and brainstem reflex components of the Full Outline of
      UnResponsiveness score showed a much wider range of mortality than the verbal
      component of Glasgow Coma Scale. In multivariable models, the Full Outline of
      UnResponsiveness score was more useful than the Glasgow Coma Scale for predicting
      mortality. CONCLUSIONS: The Full Outline of UnResponsiveness score might be a
      better prognostic tool of ICU mortality than the Glasgow Coma Scale in critically
      ill patients, most likely a result of incorporating brainstem reflexes and
      respiration into the Full Outline of UnResponsiveness score.

PMID- 25393700
TI  - Accuracy of brain multimodal monitoring to detect cerebral hypoperfusion after
      traumatic brain injury*.
AB  - OBJECTIVE: To examine the accuracy of brain multimodal monitoring-consisting of
      intracranial pressure, brain tissue PO2, and cerebral microdialysis--in detecting
      cerebral hypoperfusion in patients with severe traumatic brain injury. DESIGN:
      Prospective single-center study. PATIENTS: Patients with severe traumatic brain
      injury. SETTING: Medico-surgical ICU, university hospital. INTERVENTION:
      Intracranial pressure, brain tissue PO2, and cerebral microdialysis monitoring
      (right frontal lobe, apparently normal tissue) combined with cerebral blood flow
      measurements using perfusion CT. MEASUREMENTS AND MAIN RESULTS: Cerebral blood
      flow was measured using perfusion CT in tissue area around intracranial
      monitoring (regional cerebral blood flow) and in bilateral supra-ventricular
      brain areas (global cerebral blood flow) and was matched to cerebral physiologic
      variables. The accuracy of intracranial monitoring to predict cerebral
      hypoperfusion (defined as an oligemic regional cerebral blood flow < 35 mL/100
      g/min) was examined using area under the receiver-operating characteristic
      curves. Thirty perfusion CT scans (median, 27 hr [interquartile range, 20-45]
      after traumatic brain injury) were performed on 27 patients (age, 39 yr [24-54
      yr]; Glasgow Coma Scale, 7 [6-8]; 24/27 [89%] with diffuse injury). Regional
      cerebral blood flow correlated significantly with global cerebral blood flow
      (Pearson r = 0.70, p < 0.01). Compared with normal regional cerebral blood flow
      (n = 16), low regional cerebral blood flow (n = 14) measurements had a higher
      proportion of samples with intracranial pressure more than 20 mm Hg (13% vs 30%),
      brain tissue PO2 less than 20 mm Hg (9% vs 20%), cerebral microdialysis glucose
      less than 1 mmol/L (22% vs 57%), and lactate/pyruvate ratio more than 40 (4% vs
      14%; all p < 0.05). Compared with intracranial pressure monitoring alone (area
      under the receiver-operating characteristic curve, 0.74 [95% CI, 0.61-0.87]),
      monitoring intracranial pressure + brain tissue PO2 (area under the receiver
      operating characteristic curve, 0.84 [0.74-0.93]) or intracranial pressure +
      brain tissue PO2+ cerebral microdialysis (area under the receiver-operating
      characteristic curve, 0.88 [0.79-0.96]) was significantly more accurate in
      predicting low regional cerebral blood flow (both p < 0.05). CONCLUSION: Brain
      multimodal monitoring-including intracranial pressure, brain tissue PO2, and
      cerebral microdialysis--is more accurate than intracranial pressure monitoring
      alone in detecting cerebral hypoperfusion at the bedside in patients with severe
      traumatic brain injury and predominantly diffuse injury.

PMID- 25393702
TI  - Coenrollment in a randomized trial of high-frequency oscillation: prevalence,
      patterns, predictors, and outcomes*.
AB  - OBJECTIVE: Enrollment of individual patients into more than one study has been
      poorly evaluated. The objective of this study was to describe the characteristics
      of patients, researchers and centers involved in coenrollment, studies precluding
      coenrollment, and the prevalence, patterns, predictors, and outcomes of
      coenrollment in a randomized clinical trial. DESIGN, SETTING, METHODS: We
      conducted an observational study nested within the OSCILLation for Acute
      Respiratory Distress Syndrome Treated Early Trial, which compared high-frequency
      oscillatory ventilation to conventional ventilation. We collected patient,
      center, and study data on coenrollment in randomized patients. Multilevel
      regression examined factors independently associated with coenrollment,
      considering clustering within centers. We examined the effect of coenrollment on
      safety and the trial outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Overall, 127 of 548 randomized patients (23.2%) were coenrolled in 25 unique
      studies. Coenrollment was reported in 17 of 39 centers (43.6%). Patients were
      most commonly coenrolled in one additional randomized clinical trial (76; 59.8%).
      Coenrollment was less likely in older patients (odds ratio, 0.87; 95% CI, 0.76
      0.997), and in ICUs with greater than 26 beds (odds ratio, 0.56; 95% CI, 0.34
      0.94), and more likely by investigators with more than 11 years of experience
      (odds ratio, 1.73; 95% CI, 1.06-2.82), by research coordinators with more than 8
      years of experience (odds ratio, 1.87; 95% CI, 1.11-3.18) and in Canada (odds
      ratio, 4.66; 95% CI, 1.43-15.15). Serious adverse events were similar between
      coenrolled high-frequency oscillatory ventilation and control patients.
      Coenrollment did not modify the treatment effect of high-frequency oscillatory
      ventilation on hospital mortality. CONCLUSIONS: Coenrollment occurred in 23% of
      patients, commonly in younger patients, in smaller centers with more research
      infrastructure, and in Canada. Coenrollment did not influence patient safety or
      trial results.

PMID- 25393701
TI  - A clinical classification of the acute respiratory distress syndrome for
      predicting outcome and guiding medical therapy*.
AB  - OBJECTIVE: Current in-hospital mortality of the acute respiratory distress
      syndrome (ARDS) is above 40%. ARDS outcome depends on the lung injury severity
      within the first 24 hours of ARDS onset. We investigated whether two widely
      accepted cutoff values of PaO2/FIO2 and positive end-expiratory pressure (PEEP)
      would identify subsets of patients with ARDS for predicting outcome and guiding
      therapy. DESIGN: A 16-month (September 2008 to January 2010) prospective,
      multicenter, observational study. SETTING: Seventeen multidisciplinary ICUs in
      Spain. PATIENTS: We studied 300 consecutive, mechanically ventilated patients
      meeting American-European Consensus Conference criteria for ARDS (PaO2/FIO2 <=
      200 mm Hg) on PEEP greater than or equal to 5 cm H2O, and followed up until
      hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Based on
      threshold values for PaO2/FIO2 (150 mm Hg) and PEEP (10 cm H2O) at ARDS onset and
      at 24 hours, we assigned patients to four categories: group I (PaO2/FIO2 >= 150
      on PEEP < 10), group II (PaO2/FIO2 >= 150 on PEEP >= 10), group III (PaO2/FIO2 <
      150 on PEEP < 10), and group IV (PaO2/FIO2 < 150 on PEEP >= 10). The primary
      outcome was all-cause in-hospital mortality. Overall hospital mortality was
      46.3%. Although at study entry, patients with PaO2/FIO2 less than 150 had a
      higher mortality than patients with a PaO2/FIO2 greater than or equal to 150 (p =
      0.044), there was minimal variability in mortality among the four groups (p =
      0.186). However, classification of patients in each group changed markedly after
      24 hours of usual care. Group categorization at 24 hours provided a strong
      association with in-hospital mortality (p < 0.00001): group I had the lowest
      mortality (23.1%), whereas group IV had the highest mortality (60.3%).
      CONCLUSIONS: The degree of lung dysfunction established by a PaO2/FIO2 of 150 mm
      Hg and a PEEP of 10 cm H2O demonstrated that ARDS is not a homogeneous disorder.
      Rather, it is a series of four subsets that should be considered for enrollment
      in clinical trials and for guiding therapy. A major contribution of our study is
      the distinction between survival after 24 hours of care versus survival at the
      time of ARDS onset.

PMID- 25393704
TI  - Immediate effects of transcutaneous electrical stimulation on physiological
      swallowing effort in older versus young adults.
AB  - OBJECTIVE: This study compared the immediate impact of different transcutaneous
      electrical stimulation (TES) amplitudes on physiological swallowing effort in
      healthy older adults versus young adults. BACKGROUND: Swallowing physiology
      changes with age. Reduced physiological swallowing effort in older adults
      including lower lingua-palatal and pharyngeal pressures may increase risk for
      swallowing dysfunction (i.e. dysphagia). Transcutaneous electrical stimulation
      (TES) has been advocated as an adjunctive modality to enhance outcomes in
      exercise-based therapy for individuals with dysphagia. However, significant
      variation in how TES is applied during therapy remains and the physiological
      swallowing response to TES is poorly studied, especially in older adults.
      MATERIALS AND METHODS: Physiological change in swallowing associated with no
      stimulation, sensory stimulation and motor stimulation was compared in 20 young
      adults versus 14 older adults. Lingua-palatal and pharyngeal manometric pressures
      assessed physiological swallowing effort. RESULTS: Multivariate analyses
      identified interactions between age and stimulation amplitude on lingual and
      pharyngeal functions. Motor stimulation reduced anterior tongue pressure in both
      age groups but selectively reduced posterior lingua-palatal pressures in young
      adults only. Sensory stimulation increased base of tongue (BOT) pressures in
      older adults but decreased BOT pressures in young adults. Motor stimulation
      increased hypopharyngeal pressures in both groups. CONCLUSION: Age and TES level
      interact in determining immediate physiological responses on swallow performance.
      A one-size-fit-all approach to TES in dysphagia rehabilitation may be
      misdirected.

PMID- 25393703
TI  - ABCD1 deletion-induced mitochondrial dysfunction is corrected by SAHA:
      implication for adrenoleukodystrophy.
AB  - X-linked Adrenoleukodystrophy (X-ALD), an inherited peroxisomal metabolic
      neurodegenerative disorder, is caused by mutations/deletions in the ATP-binding
      cassette transporter (ABCD1) gene encoding peroxisomal ABC transporter
      adrenoleukodystrophy protein (ALDP). Metabolic dysfunction in X-ALD is
      characterized by the accumulation of very long chain fatty acids >= C22:0) in the
      tissues and plasma of patients. Here, we investigated the mitochondrial status
      following deletion of ABCD1 in B12 oligodendrocytes and U87 astrocytes. This
      study provides evidence that silencing of peroxisomal protein ABCD1 produces
      structural and functional perturbations in mitochondria. Activities of electron
      transport chain-related enzymes and of citric acid cycle (TCA cycle) were
      reduced; mitochondrial redox status was dysregulated and the mitochondrial
      membrane potential was disrupted following ABCD1 silencing. A greater reduction
      in ATP levels and citrate synthase activities was observed in oligodendrocytes as
      compared to astrocytes. Furthermore, most of the mitochondrial perturbations
      induced by ABCD1 silencing were corrected by treating cells with suberoylanilide
      hydroxamic acid, an Histone deacetylase inhibitor. These observations indicate a
      novel relationship between peroxisomes and mitochondria in cellular homeostasis
      and the importance of intact peroxisomes in relation to mitochondrial integrity
      and function in the cell types that participate in the pathobiology of X-ALD.
      These observations suggest suberoylanilide hydroxamic acid as a potential therapy
      for X-ALD. Schematic description of the effects of loss of peroxisomal ATP
      binding cassette transporter D1 (ABCD1) gene on cellular Redox and mitochondrial
      activities and their correction by suberoylanilide hydroxamic acid (SAHA)
      treatment. Pathogenomic accumulation of very long chain fatty acids (VLCFA) as a
      result of loss of ABCD1 leads to dysfunctions of mitochondrial biogenesis and its
      activities. Treatment with SAHA corrects mitochondrial dysfunctions. These
      studies describe unique cooperation between mitochondria and peroxisome for
      cellular activities.

PMID- 25393705
TI  - Chronic cocaine administration induces long-term impairment in the drive to
      obtain natural reinforcers in high- but not low-demanding tasks.
AB  - Repeated drug exposure induces short- and long-term neuroadaptations in brain
      reward circuitries that are normally involved in the regulation of motivation.
      Hence, repeated drug exposure has been suggested to also affect the drive to
      acquire natural reinforcers. Here, we tested how chronic exposure of rats to
      cocaine, as well as a subsequent withdrawal period, affects acquisition of
      natural reinforcers in high- and low-demanding tasks (HD and LD tasks,
      respectively). We chronically administered cocaine (i.p., 15 mg/kg once daily, or
      saline in control) for 30 days, followed by a 30-day withdrawal period. We tested
      the effect of this treatment on the acquisition of two natural appetitive
      reinforcers, namely self-administering a 10% sucrose solution and mounting a
      receptive female, under LD and HD conditions. During the cocaine exposure period,
      behavioral testing took place 18 hours after cocaine injection, namely after the
      acute pharmacologic effect of the drug dissipated. We show that chronic i.p.
      cocaine exposure decreased procurement of both reinforcers in HD but not in LD
      tasks. The effect was observed throughout the administration period with partial
      recovery after withdrawal. Taken together, we present empirical evidence that
      chronic exposure to a constant dose of cocaine is sufficient to reduce natural
      reinforcement, and that this decrease can outlast drug exposure. Importantly,
      such effects are observed only when high demands are opposing the consumption of
      the natural reinforcer.

PMID- 25393706
TI  - Evidence for the chain-growth synthesis of statistical pi-conjugated donor
      acceptor copolymers.
AB  - The synthesis of a series of dithienosilole-benzotriazole donor-acceptor
      statistical copolymers with various donor-acceptor ratios is reported, prepared
      by Kumada catalyst-transfer polymerization. Statistical copolymer structure is
      verified by (1) H NMR and optical absorption spectroscopy, and supported by
      density functional theory (DFT) calculations. The copolymers exhibit a single
      optical absorption band that lies between dithienosilole and benzotriazole
      homopolymers, which shifts with varying donor-acceptor content. A chain extension
      experiment using a partially consumed benzotriazole solution as a macroinitiator
      followed by addition of dithienosilole leads to the synthesis of a statistical
      dithienosilole-benzotriazole block copolymer from a pure benzotriazole block,
      demonstrating that both chain extension and simultaneous monomer incorporation
      are possible using this methodology. 

PMID- 25393707
TI  - A novel approach to monitor the hydrolysis of barley (Hordeum vulgare L) malt: a
      chemometrics approach.
AB  - Malting barley is a process that has been profusely studied and is known to be
      influenced by several physical and biochemical properties of the grain. In
      particular, the amount of material that can be extracted from the malt (malt
      extract) is an important measure of brewing performance and end quality. The
      objectives of this study were (a) to compare the time course of hydrolysis of
      different malting barley (Hordeum vulgare L) varieties and (b) to evaluate the
      usefulness of mid-infrared (MIR) spectroscopy as high-throughput method to
      monitor malt hydrolysis. Differences in the pattern of hydrolysis were observed
      between the malt samples analyzed where samples from the same variety that have
      similar hot water extract (HWE) values tend to have the same pattern of
      hydrolysis. Principal component score plots based on the MIR spectra showed
      similar results. Partial least-squares discriminate analysis (PLS-DA) was used to
      classify malt samples according to their corresponding variety and time course of
      hydrolysis. The coefficient of determination (R(2)) and the standard error of
      cross validation (SECV) obtained for the prediction of variety and time course of
      hydrolysis were 0.67 (1.01) and 0.38 (19.90), respectively. These differences
      might be the result of the different composition in sugars between the barley
      varieties analyzed after malting, measured as wort density and not observed when
      only the HWE value at the end point is reported. This method offers the
      possibility to measure several parameters in malt simultaneously, reducing the
      time of analysis as well as requiring minimal sample preparation. 

PMID- 25393708
TI  - Changes of flavor compounds of hydrolyzed chicken bone extracts during Maillard
      reaction.
AB  - Flavor quality, including non-volatile and volatile compounds, of hydrolyzed
      chicken bone extracts (HCBE) during Maillard reaction (MR) was evaluated with
      HPLC, tasting sensory system, Electronic-Nose (E-nose), and GC-MS. Results showed
      that flavor amino acids (AA) accounted for 72% to 74% of total free AA in HCBE.
      Taste of umami increased first and then decreased during MR, while equivalent
      umami concentration remained at a stable level. Results of taste sensing system
      and bitter AA showed that MR could reduce the bitter taste of HCBE significantly.
      E-Nose test showed there are great changes of volatile flavor during MR. And
      total of 59 volatile compounds were identified in HCBE during MR, which should
      responsible for the increase of flavor in HCBE. Our results indicated that MR
      could be used as an effective way to change the flavor compounds in HCBE, and
      therefore provide a strategy for preparation of meaty flavor enhancer from bone
      residue as a byproduct of meat industry. 

PMID- 25393709
TI  - Online two-dimensional porous graphitic carbon/reversed phase liquid
      chromatography platform applied to shotgun proteomics and glycoproteomics.
AB  - A novel fully automatable two-dimensional liquid chromatography (2DLC) platform
      has been integrated into a modified commercial off-the-shelf LC instrument,
      incorporating porous graphitic carbon (PGC) separation and conventional low-pH
      reversed-phase (RP) separation for both proteomics and N-glycomics analyses; the
      dual-trap column configuration of this platform offers desirable high-throughput
      analyses with almost no idle time, in addition to a miniaturized setup and
      simplified operation. The total run time per analysis was only 19 h when using
      eight PGC fractions for unattended large-scale qualitative and quantitative
      proteomic analyses; the identification of 2678 nonredundant proteins and 11,984
      unique peptides provided one of the most comprehensive proteome data sets for
      primary cerebellar granule neurons (CGNs). The effect of pH on the PGC column was
      investigated for the first time to improve the hydrophobic peptide coverage; the
      performance of the optimized system was first benchmarked using tryptic digests
      of Saccharomyces cerevisiae cell lysates and then evaluated through duplicate
      analyses of Macaca fascicularis cerebral cortex lysates using isobaric tags for
      relative and absolute quantitation (iTRAQ) technology. An additional plug-and
      play PGC module functioned in a complementary manner to recover unretained
      hydrophilic solutes from the low-pH RP column; synchronization of the
      fractionations between the PGC-RP system and the PGC module facilitated
      simultaneous analyses of hydrophobic and hydrophilic compounds from a single
      sample injection event. This methodology was applied to perform, for the first
      time, detailed glycomics analyses of Macaca fascicularis plasma, resulting in the
      identification of a total 130 N-glycosylated plasma proteins, 705 N
      glycopeptides, and 254 N-glycosylation sites.

PMID- 25393710
TI  - Automated method for determination of dissolved organic carbon-water distribution
      constants of structurally diverse pollutants using pre-equilibrium solid-phase
      microextraction.
AB  - Dissolved organic carbon (DOC) plays a key role in determining the environmental
      fate of semivolatile organic environmental contaminants. The goal of the present
      study was to develop a method using commercially available hardware to rapidly
      characterize the sorption properties of DOC in water samples. The resulting
      method uses negligible-depletion direct immersion solid-phase microextraction
      (SPME) and gas chromatography-mass spectrometry. Its performance was evaluated
      using Nordic reference fulvic acid and 40 priority environmental contaminants
      that cover a wide range of physicochemical properties. Two SPME fibers had to be
      used to cope with the span of properties, 1 coated with polydimethylsiloxane and
      1 coated with polystyrene divinylbenzene polydimethylsiloxane, for nonpolar and
      semipolar contaminants, respectively. The measured DOC-water distribution
      constants showed reasonably good reproducibility (standard deviation <= 0.32) and
      good correlation (R(2)  = 0.80) with log octanol-water partition coefficients for
      nonpolar persistent organic pollutants. The sample pretreatment is limited to
      filtration, and the method is easy to adjust to different DOC concentrations.
      These experiments also utilized the latest SPME automation that largely decreases
      total cycle time (to 20 min or shorter) and increases sample throughput, which is
      advantageous in cases when many samples of DOC must be characterized or when the
      determinations must be performed quickly, for example, to avoid precipitation,
      aggregation, and other changes of DOC structure and properties. The data
      generated by this method are valuable as a basis for transport and fate modeling
      studies.

PMID- 25393711
TI  - Capric Acid Absorption in the Presence of Hydroxypropyl-beta-Cyclodextrin in the
      Rat Ileum using the In Situ Single-Pass Perfusion Technique.
AB  - The purpose of the present study was to gain quantitative mechanistic insight
      into the role cyclodextrin carriers may play in the intestinal absorption of
      highly lipophilic molecules. The physical model approach was employed to
      investigate capric acid absorption in the rat ileum using the in situ single-pass
      method with 2-hydroxypropyl-beta-cyclodextrin (HPB) present in the perfusate. Two
      physical models were examined: the flat surface model in which the intestinal
      wall was treated as a hollow, smooth, circular cylinder, and the villus model in
      which the intestinal surface allowed for the presence of villi. Capric acid
      absorption was found to be essentially 100% aqueous boundary layer controlled at
      low HPB concentrations and increasingly membrane controlled at the higher HPB
      concentrations. Theoretical calculations based on the experimental data and model
      parameters were found to be consistent with: at low HPB concentrations, capric
      acid was mainly absorbed at the villus tips and there was very little capric acid
      penetration into the intervillus space; in contrast, at 50 mM HPB, there was
      considerable capric acid penetration into the intervillus space, this
      corresponding to around a 4.5-fold increase in the accessible area for absorption
      when compared with 0 mM HPB.

PMID- 25393712
TI  - Pinosylvin at a high concentration induces AMPK-mediated autophagy for preventing
      necrosis in bovine aortic endothelial cells.
AB  - Pinosylvin is a known functional compound of the Pinus species. Pinosylvin at low
      concentrations (~ pmol/L) was reported to promote cell proliferation in
      endothelial cells. However, this study found that pinosylvin at a high
      concentration (100 MUmol/L) induces cell death in bovine aortic endothelial
      cells. Therefore, we examined how pinosylvin was associated with apoptosis,
      autophagy, and necrosis. Pinosylvin at a high concentration appeared to promote
      caspase-3 activation, nuclear condensation, and the "flip-flop" of
      phosphatidylserine, indicating that pinosylvin induces apoptosis. However, based
      on flow cytometry data obtained from double-staining with annexin V and propidium
      iodide, pinosylvin was shown to inhibit necrosis, a postapoptotic process.
      Pinosylvin induced LC3 conversion from LC3-I to LC3-II and p62 degradation, which
      are important indicators of autophagy. In addition, AMP-activated protein kinase
      (AMPK) appeared to be activated by pinosylvin, and an AMPK inhibitor was markedly
      shown to reduce the LC3 conversion. The inhibitory effect of an AMPK inhibitor
      was reversed by pinosylvin. These results suggest that pinosylvin induces
      autophagy via AMPK activation. Further, necrosis was found to be promoted by an
      autophagy inhibitor and then restored by pinosylvin, while the caspase-3
      inhibitor had no effect on necrosis. These findings indicate that pinosylvin
      induced autophagy blocks necrotic progress in endothelial cells.

PMID- 25393713
TI  - Recombinant human soluble thrombomodulin and mortality in severe pneumonia
      patients with sepsis-associated disseminated intravascular coagulation: an
      observational nationwide study.
AB  - BACKGROUND: The association between recombinant human soluble thrombomodulin
      (rhTM) use and mortality in patients with sepsis-associated disseminated
      intravascular coagulation (DIC) remains controversial. OBJECTIVES: To examine the
      hypothesis that rhTM could be effective in the treatment of patients with sepsis
      associated DIC following severe pneumonia. METHODS: Propensity score and
      instrumental variable analyses using a nationwide administrative database, the
      Japanese Diagnosis Procedure Combination inpatient database, were used. The main
      outcome was 28-day in-hospital all-cause mortality. RESULTS: Eligible patients (n
      = 6342) from 936 hospitals were categorized into the rhTM group (n = 1280) or
      control group (n = 5062). Propensity score matching created a matched cohort of
      1140 pairs with and without rhTM. No significant difference in 28-day mortality
      was documented between the two groups in the unmatched analysis (rhTM vs.
      control, 37.0%, 474/1280 vs. 36.9%, 1866/5062; odds ratio [OR], 1.00; 95%CI, 0.98
      1.03), nor in the propensity-matched analysis (37.6%, 429/1140 vs. 37.0%,
      886/1140; OR, 1.01; 95%CI, 0.93-1.10). The logistic regression analysis did not
      show a significant association between the use of rhTM and 28-day mortality in
      propensity-matched patients (OR, 1.00; 95%CI, 0.87-1.22). An analysis using the
      hospital rhTM-prescribing rate as an instrumental variable found that receipt of
      rhTM was not associated with reduction in mortality at 28 days (risk difference,
      0.008; 95% CI, -0.08-0.98). CONCLUSIONS: This large retrospective nationwide
      study demonstrated that there might be little association between the use of rhTM
      and mortality in severe pneumonia patients with sepsis-associated DIC. A
      multinational randomized trial is required to confirm this.

PMID- 25393714
TI  - Using the Transtheoretical Model to Examine the Effects of Exergaming on Physical
      Activity Among Children.
AB  - BACKGROUND: The Transtheoretical Model (TTM) has been widely used to understand
      individuals' physical activity (PA) correlates and behavior. However, the
      theory's application among children in exergaming remains unknown. PURPOSE:
      Investigate the effects of an exergaming program on children's TTM-based PA
      correlates and PA levels. METHODS: At pretest and posttest, 212 upper elementary
      children (mean age = 11.17 years) from the greater Mountain West Region were
      administered measures regarding stages of change (SOC) for PA behavior,
      decisional balance for PA behaviors, PA self-efficacy, and self-reported PA
      levels. Following the pretest, a weekly 30-minute, 18-week Dance Dance Revolution
      (DDR) program was implemented. Children were classified into 3 SOC groups:
      progressive children (ie, progressed to a higher SOC stage); stable children (ie,
      remained at the same SOC stage); and regressive children (ie, regressed to a
      lower SOC stage). RESULTS: Progressive children had greater increased PA levels
      than regressive children (P < .01) from pretest to posttest. Similarly,
      progressive children had greater increased self-efficacy (P < .05) and decision
      balance (P < .05) than regressive children. CONCLUSIONS: The findings indicate
      that progressive children had more improvements on self-efficacy, decisional
      balance, and PA levels than regressive children over time. Implications of
      findings are discussed.

PMID- 25393715
TI  - Back-propagation operation for analog neural network hardware with synapse
      components having hysteresis characteristics.
AB  - To realize an analog artificial neural network hardware, the circuit element for
      synapse function is important because the number of synapse elements is much
      larger than that of neuron elements. One of the candidates for this synapse
      element is a ferroelectric memristor. This device functions as a voltage
      controllable variable resistor, which can be applied to a synapse weight.
      However, its conductance shows hysteresis characteristics and dispersion to the
      input voltage. Therefore, the conductance values vary according to the history of
      the height and the width of the applied pulse voltage. Due to the difficulty of
      controlling the accurate conductance, it is not easy to apply the back
      propagation learning algorithm to the neural network hardware having memristor
      synapses. To solve this problem, we proposed and simulated a learning operation
      procedure as follows. Employing a weight perturbation technique, we derived the
      error change. When the error reduced, the next pulse voltage was updated
      according to the back-propagation learning algorithm. If the error increased the
      amplitude of the next voltage pulse was set in such way as to cause similar
      memristor conductance but in the opposite voltage scanning direction. By this
      operation, we could eliminate the hysteresis and confirmed that the simulation of
      the learning operation converged. We also adopted conductance dispersion
      numerically in the simulation. We examined the probability that the error
      decreased to a designated value within a predetermined loop number. The
      ferroelectric has the characteristics that the magnitude of polarization does not
      become smaller when voltages having the same polarity are applied. These
      characteristics greatly improved the probability even if the learning rate was
      small, if the magnitude of the dispersion is adequate. Because the dispersion of
      analog circuit elements is inevitable, this learning operation procedure is
      useful for analog neural network hardware. 

PMID- 25393716
TI  - Seroprevalence and spatial epidemiology of Lymphatic Filariasis in American Samoa
      after successful mass drug administration.
AB  - BACKGROUND: As part of the Global Programme to Eliminate Lymphatic Filariasis
      (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006, and
      passed transmission assessment surveys in 2011-2012. We examined the
      seroprevalence and spatial epidemiology of LF post-MDA to inform strategies for
      ongoing surveillance and to reduce resurgence risk. METHODS: ELISA for LF antigen
      (Og4C3) and antibodies (Wb123, Bm14) were performed on a geo-referenced serum
      bank of 807 adults collected in 2010. Risk factors assessed for association with
      sero-positivity included age, sex, years lived in American Samoa, and occupation.
      Geographic clustering of serological indicators was investigated to identify
      spatial dependence and household-level clustering. RESULTS: Og4C3 antigen of >128
      units (positive) were found in 0.75% (95% CI 0.3-1.6%) of participants, and >32
      units (equivocal plus positive) in 3.2% (95% CI 0.6-4.7%). Seroprevalence of
      Wb123 and Bm14 antibodies were 8.1% (95% CI 6.3-10.2%) and 17.9% (95% CI 15.3
      20.7%) respectively. Antigen-positive individuals were identified in all ages,
      and antibody prevalence higher in older ages. Prevalence was higher in males, and
      inversely associated with years lived in American Samoa. Spatial distribution of
      individuals varied significantly with positive and equivocal levels of Og4C3
      antigen, but not with antibodies. Using Og4C3 cutoff points of >128 units and >32
      units, average cluster sizes were 1,242 m and 1,498 m, and geographical proximity
      of households explained 85% and 62% of the spatial variation respectively.
      CONCLUSIONS: High-risk populations for LF in American Samoa include adult males
      and recent migrants. We identified locations and estimated the size of possible
      residual foci of antigen-positive adults, demonstrating the value of spatial
      analysis in post-MDA surveillance. Strategies to monitor cluster residents and
      high-risk groups are needed to reduce resurgence risk. Further research is
      required to quantify factors contributing to LF transmission at the last stages
      of elimination to ensure that programme achievements are sustained.

PMID- 25393718
TI  - PET-CT for assessing mediastinal lymph node involvement in patients with
      suspected resectable non-small cell lung cancer.
AB  - BACKGROUND: A major determinant of treatment offered to patients with non-small
      cell lung cancer (NSCLC) is their intrathoracic (mediastinal) nodal status. If
      the disease has not spread to the ipsilateral mediastinal nodes, subcarinal (N2)
      nodes, or both, and the patient is otherwise considered fit for surgery,
      resection is often the treatment of choice. Planning the optimal treatment is
      therefore critically dependent on accurate staging of the disease. PET-CT
      (positron emission tomography-computed tomography) is a non-invasive staging
      method of the mediastinum, which is increasingly available and used by lung
      cancer multidisciplinary teams. Although the non-invasive nature of PET-CT
      constitutes one of its major advantages, PET-CT may be suboptimal in detecting
      malignancy in normal-sized lymph nodes and in ruling out malignancy in patients
      with coexisting inflammatory or infectious diseases. OBJECTIVES: To determine the
      diagnostic accuracy of integrated PET-CT for mediastinal staging of patients with
      suspected or confirmed NSCLC that is potentially suitable for treatment with
      curative intent. SEARCH METHODS: We searched the following databases up to 30
      April 2013: The Cochrane Library, MEDLINE via OvidSP (from 1946), Embase via
      OvidSP (from 1974), PreMEDLINE via OvidSP, OpenGrey, ProQuest Dissertations &
      Theses, and the trials register www.clinicaltrials.gov. There were no language or
      publication status restrictions on the search. We also contacted researchers in
      the field, checked reference lists, and conducted citation searches (with an end
      date of 9 July 2013) of relevant studies. SELECTION CRITERIA: Prospective or
      retrospective cross-sectional studies that assessed the diagnostic accuracy of
      integrated PET-CT for diagnosing N2 disease in patients with suspected resectable
      NSCLC. The studies must have used pathology as the reference standard and
      reported participants as the unit of analysis. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted data pertaining to the study characteristics and
      the number of true and false positives and true and false negatives for the index
      test, and they independently assessed the quality of the included studies using
      QUADAS-2. We calculated sensitivity and specificity with 95% confidence intervals
      (CI) for each study and performed two main analyses based on the criteria for
      test positivity employed: Activity > background or SUVmax >= 2.5 (SUVmax =
      maximum standardised uptake value), where we fitted a summary receiver operating
      characteristic (ROC) curve using a hierarchical summary ROC (HSROC) model for
      each subset of studies. We identified the average operating point on the SROC
      curve and computed the average sensitivities and specificities. We checked for
      heterogeneity and examined the robustness of the meta-analyses through
      sensitivity analyses. MAIN RESULTS: We included 45 studies, and based on the
      criteria for PET-CT positivity, we categorised the included studies into three
      groups: Activity > background (18 studies, N = 2823, prevalence of N2 and N3
      nodes = 679/2328), SUVmax >= 2.5 (12 studies, N = 1656, prevalence of N2 and N3
      nodes = 465/1656), and Other/mixed (15 studies, N = 1616, prevalence of N2 to N3
      nodes = 400/1616). None of the studies reported (any) adverse events. Under
      reporting generally hampered the quality assessment of the studies, and in 30/45
      studies, the applicability of the study populations was of high or unclear
      concern.The summary sensitivity and specificity estimates for the 'Activity >
      background PET-CT positivity criterion were 77.4% (95% CI 65.3 to 86.1) and 90.1%
      (95% CI 85.3 to 93.5), respectively, but the accuracy estimates of these studies
      in ROC space showed a wide prediction region. This indicated high between-study
      heterogeneity and a relatively large 95% confidence region around the summary
      value of sensitivity and specificity, denoting a lack of precision. Sensitivity
      analyses suggested that the overall estimate of sensitivity was especially
      susceptible to selection bias; reference standard bias; clear definition of test
      positivity; and to a lesser extent, index test bias and commercial funding bias,
      with lower combined estimates of sensitivity observed for all the low 'Risk of
      bias' studies compared with the full analysis.The summary sensitivity and
      specificity estimates for the SUVmax >= 2.5 PET-CT positivity criterion were
      81.3% (95% CI 70.2 to 88.9) and 79.4% (95% CI 70 to 86.5), respectively.In this
      group, the accuracy estimates of these studies in ROC space also showed a very
      wide prediction region. This indicated very high between-study heterogeneity, and
      there was a relatively large 95% confidence region around the summary value of
      sensitivity and specificity, denoting a clear lack of precision. Sensitivity
      analyses suggested that both overall accuracy estimates were marginally sensitive
      to flow and timing bias and commercial funding bias, which both lead to slightly
      lower estimates of sensitivity and specificity.Heterogeneity analyses showed that
      the accuracy estimates were significantly influenced by country of study origin,
      percentage of participants with adenocarcinoma, (18F)-2-fluoro-deoxy-D-glucose
      (FDG) dose, type of PET-CT scanner, and study size, but not by study design,
      consecutive recruitment, attenuation correction, year of publication, or
      tuberculosis incidence rate per 100,000 population. AUTHORS' CONCLUSIONS: This
      review has shown that accuracy of PET-CT is insufficient to allow management
      based on PET-CT alone. The findings therefore support National Institute for
      Health and Care (formally 'clinical') Excellence (NICE) guidance on this topic,
      where PET-CT is used to guide clinicians in the next step: either a biopsy or
      where negative and nodes are small, directly to surgery. The apparent difference
      between the two main makes of PET-CT scanner is important and may influence the
      treatment decision in some circumstances. The differences in PET-CT accuracy
      estimates between scanner makes, NSCLC subtypes, FDG dose, and country of study
      origin, along with the general variability of results, suggest that all large
      centres should actively monitor their accuracy. This is so that they can make
      reliable decisions based on their own results and identify the populations in
      which PET-CT is of most use or potentially little value.

PMID- 25393717
TI  - Effects of oral and intravenous administration of buspirone on food-cocaine
      choice in socially housed male cynomolgus monkeys.
AB  - Drugs acting at D3 dopamine receptors have been suggested as medications for
      cocaine dependence. These experiments examined the effects of intravenously and
      orally administered buspirone, a D2-like receptor antagonist with high affinity
      for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group
      housed male cynomolgus monkeys. Use of socially housed monkeys permitted the
      assessment of whether social status, known to influence D2-like receptor
      availability, modulates the behavioral effects of buspirone. Buspirone was
      administered acutely to monkeys self-administering cocaine under a food-drug
      choice procedure in which a cocaine self-administration dose-effect curve was
      determined daily. When administered by either route, buspirone significantly
      decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys,
      however, i.v. buspirone was ineffective on average, and oral buspirone increased
      choice of lower cocaine doses. The effects of buspirone only differed according
      to route of administration in subordinate monkeys. Moreover, it is noteworthy
      that the effects of buspirone were similar to those of the D3 receptor-selective
      antagonist PG01037 and qualitatively different than those of less selective drugs
      that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly
      D4 receptor mechanism of action for buspirone. Taken together, the data support
      the utility of drugs targeting D3/D4 receptors as potential treatments for
      cocaine addiction, particularly in combination with enriching environmental
      manipulations. 

PMID- 25393719
TI  - DNAJC13 genetic variants in parkinsonism.
AB  - BACKGROUND: A novel mutation (p.N855S) in DNAJC13 has been linked to familial,
      late-onset Lewy body parkinsonism in a Dutch-German-Russian Mennonite multi
      incident kindred. METHODS: DNAJC13 was sequenced in 201 patients with
      parkinsonism and 194 controls from Canada. Rare (minor allele frequency < 0.01)
      missense variants identified in patients were genotyped in two Parkinson's
      disease case-controls cohorts. RESULTS: Eighteen rare missense mutations were
      identified; four were observed in controls, three were observed in both patients
      and controls, and eleven were identified only in patients. Subsequent genotyping
      showed p.E1740Q and p.L2170W to be more frequent in patients, and p.R1516H being
      more frequent in controls. Additionally, p.P336A, p.V722L, p.N855S, p.R1266Q were
      seen in one patient each, and p.T1895M was found in two patients. CONCLUSION:
      Although the contribution of rare genetic variation in DNAJC13 to parkinsonisms
      remains to be further elucidated, this study suggests that, in addition to
      p.N855S, other rare variants might affect disease susceptibility.

PMID- 25393720
TI  - Modelling the influence of Major Baltic Inflows on near-bottom conditions at the
      entrance of the Gulf of Finland.
AB  - A coupled hydrodynamic-biogeochemical model was implemented in order to estimate
      the effects of Major Baltic Inflows on the near-bottom hydrophysical and
      biogeochemical conditions in the northern Baltic Proper and the western Gulf of
      Finland during the period 1991-2009. We compared results of a realistic reference
      run to the results of an experimental run where Major Baltic Inflows were
      suppressed. Further to the expected overall decrease in bottom salinity, this
      modelling experiment confirms that in the absence of strong saltwater inflows the
      deep areas of the Baltic Proper would become more anoxic, while in the shallower
      areas (western Gulf of Finland) near-bottom average conditions improve. Our
      experiment revealed that typical estuarine circulation results in the sporadic
      emergence of short-lasting events of near-bottom anoxia in the western Gulf of
      Finland due to transport of water masses from the Baltic Proper. Extrapolating
      our results beyond the modelled period, we speculate that the further deepening
      of the halocline in the Baltic Proper is likely to prevent inflows of anoxic
      water to the Gulf of Finland and in the longer term would lead to improvement in
      near-bottom conditions in the Baltic Proper. Our results reaffirm the importance
      of accurate representation of salinity dynamics in coupled Baltic Sea models
      serving as a basis for credible hindcast and future projection simulations of
      biogeochemical conditions. 

PMID- 25393721
TI  - ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh
      syndrome.
AB  - The human ECHS1 gene encodes the short-chain enoyl coenzyme A hydratase, the
      enzyme that catalyzes the second step of beta-oxidation of fatty acids in the
      mitochondrial matrix. We report on a boy with ECHS1 deficiency who was diagnosed
      with Leigh syndrome at 21 months of age. The patient presented with hypotonia,
      metabolic acidosis, and developmental delay. A combined respiratory chain
      deficiency was also observed. Targeted exome sequencing of 776 mitochondria
      associated genes encoded by nuclear DNA identified compound heterozygous
      mutations in ECHS1. ECHS1 protein expression was severely depleted in the
      patient's skeletal muscle and patient-derived myoblasts; a marked decrease in
      enzyme activity was also evident in patient-derived myoblasts. Immortalized
      patient-derived myoblasts that expressed exogenous wild-type ECHS1 exhibited the
      recovery of the ECHS1 activity, indicating that the gene defect was pathogenic.
      Mitochondrial respiratory complex activity was also mostly restored in these
      cells, suggesting that there was an unidentified link between deficiency of ECHS1
      and respiratory chain. Here, we describe the patient with ECHS1 deficiency; these
      findings will advance our understanding not only the pathology of mitochondrial
      fatty acid beta-oxidation disorders, but also the regulation of mitochondrial
      metabolism.

PMID- 25393722
TI  - Multi-parametric representation of voxel-based quantitative magnetic resonance
      imaging.
AB  - The aim of the study was to explore the possibilities of multi-parametric
      representations of voxel-wise quantitative MRI data to objectively discriminate
      pathological cerebral tissue in patients with brain disorders. For this purpose,
      we recruited 19 patients with Multiple Sclerosis (MS) as benchmark samples and 19
      age and gender matched healthy subjects as a reference group. The subjects were
      examined using quantitative Magnetic Resonance Imaging (MRI) measuring the tissue
      structure parameters: relaxation rates, R(1) and R(2), and proton density. The
      resulting parameter images were normalized to a standard template. Tissue
      structure in MS patients was assessed by voxel-wise comparisons with the
      reference group and with correlation to a clinical measure, the Expanded
      Disability Status Scale (EDSS). The results were visualized by conventional
      geometric representations and also by multi-parametric representations. Data
      showed that MS patients had lower R(1) and R(2), and higher proton density in
      periventricular white matter and in wide-spread areas encompassing central and
      sub-cortical white matter structures. MS-related tissue abnormality was
      highlighted in posterior white matter whereas EDSS correlation appeared
      especially in the frontal cortex. The multi-parameter representation highlighted
      disease-specific features. In conclusion, the proposed method has the potential
      to visualize both high-probability focal anomalies and diffuse tissue changes.
      Results from voxel-based statistical analysis, as exemplified in the present
      work, may guide radiologists where in the image to inspect for signs of disease.
      Future clinical studies must validate the usability of the method in clinical
      practice.

PMID- 25393723
TI  - RSV: Immunoprophylaxis and non-invasive respiratory support in ex-preterms: A
      northern UK perspective.
AB  - Recent guidance has suggested that immunoprophylaxis with monoclonal antibody
      against respiratory syncytial virus (RSV) should be extended to ex-preterm
      infants who are moderate-to-late-preterm and discharged home during the RSV
      season. Noninvasive respiratory support (NIV) for infants with bronchiolitis is
      becoming widespread with little supporting evidence for efficacy over nonpressure
      support methods. We used multicentre prospective audit and service evaluation to
      evaluate whether extension of current practice in line with the guidance would
      provide a clinical or cost benefit, and whether NIV provides any benefits in the
      ex-preterm population. The prevalence of bronchiolitic illness requiring
      admission in our population was similar to other studies (2.5%). We found that
      the majority of ex-preterm infants with RSV positive bronchiolitis who required
      NIV did not meet the extended criteria for immunisation. Our data suggest that
      extending RSV prophylaxis as recommended would be unlikely to reduce numbers of
      infants requiring respiratory support for RSV. NIV use has been widely adopted
      (9% of 'bronchiolitic' admissions) in our region but the data do not support it
      as a useful adjunct for ex-preterms with RSV positive illness requiring
      respiratory support: it does not appear to reduce the need for subsequent formal
      ventilation. Our study does not support a case for change to more widespread,
      protocol driven immunisation for RSV. Further research is needed in a randomised,
      controlled setting to examine the use of NIV in bronchiolitis in a wider context.

PMID- 25393727
TI  - Construction of nitronyl nitroxide-based 3d-4f clusters: structure and magnetism.
AB  - Three unprecedented nitronyl nitroxide radical-bridged 3d-4f clusters, [Ln2 Cu2
      (hfac)10 (NIT-3py)2 (H2 O)2 ](Ln(III) =Y, Gd, Dy), have been obtained from the
      self-assembly of Ln(hfac)3 , Cu(hfac)2 , and the radical ligand. The Dy complex
      shows a slow relaxation of magnetization, representing the first nitronyl
      nitroxide radical-based 3d-4f cluster with single-molecule magnet behavior. 

PMID- 25393728
TI  - Functional supramolecular polymers for biomedical applications.
AB  - As a novel class of dynamic and non-covalent polymers, supramolecular polymers
      not only display specific structural and physicochemical properties, but also
      have the ability to undergo reversible changes of structure, shape, and function
      in response to diverse external stimuli, making them promising candidates for
      widespread applications ranging from academic research to industrial fields. By
      an elegant combination of dynamic/reversible structures with exceptional
      functions, functional supramolecular polymers are attracting increasing attention
      in various fields. In particular, functional supramolecular polymers offer
      several unique advantages, including inherent degradable polymer backbones, smart
      responsiveness to various biological stimuli, and the ease for the incorporation
      of multiple biofunctionalities (e.g., targeting and bioactivity), thereby showing
      great potential for a wide range of applications in the biomedical field. In this
      Review, the trends and representative achievements in the design and synthesis of
      supramolecular polymers with specific functions are summarized, as well as their
      wide-ranging biomedical applications such as drug delivery, gene transfection,
      protein delivery, bio-imaging and diagnosis, tissue engineering, and biomimetic
      chemistry. These achievements further inspire persistent efforts in an emerging
      interdisciplin-ary research area of supramolecular chemistry, polymer science,
      material science, biomedical engineering, and nanotechnology. 

PMID- 25393729
TI  - Short sleep duration and childhood obesity: cross-sectional analysis in Peru and
      patterns in four developing countries.
AB  - BACKGROUND: We aimed to describe the patterns of nutritional status and sleep
      duration in children from Ethiopia, India, Peru and Vietnam; to assess the
      association between short sleep duration and overweight and obesity, and if this
      was similar among boys and girls in Peru. METHODS AND FINDINGS: Analysis of the
      Young Lives Study, younger cohort, third round. In Ethiopia there were 1,999
      observations, 2,011, 2,052 and 2,000 in India, Peru and Vietnam, respectively.
      Analyses included participants with complete data for sleep duration, BMI, sex
      and age; missing data: 5.9% (Ethiopia), 4.1% (India), 6.0% (Peru) and 4.5%
      (Vietnam). Exposure was sleep duration per day: short (<10 hours) versus regular
      (10-11 hours). Outcome was overweight and obesity. Multivariable analyses were
      conducted using a hierarchical approach to assess the effect of variables at
      different levels. Overweight/obesity prevalence was 0.5%/0.2% (Ethiopia),
      1.3%/0.3% (India), 6.1%/2.8% (Vietnam), and 15.8%/5.4% (Peru). Only Peruvian data
      was considered to explore the association between short sleep duration and
      overweight and obesity, with 1,929 children, aged 7.9+/-0.3 years, 50.3% boys.
      Short and regular sleep duration was 41.6% and 55.6%, respectively. Multivariable
      models showed that obesity was 64% more prevalent among children with short sleep
      duration, an estimate that lost significance after controlling for individual-
      and family-related variables (PR: 1.15; 95%CI: 0.81-1.64). Gender was an effect
      modifier of the association between short sleep duration and overweight (p =
      0.030) but not obesity (p = 0.533): the prevalence ratio was greater than one
      across all the models for boys, yet it was less than one for girls. CONCLUSIONS:
      Childhood overweight and obesity have different profiles across developing
      settings. In a sample of children living in resource-limited settings in Peru
      there is no association between short sleep duration and obesity; the crude
      association was slightly attenuated by children-related variables but strongly
      diminished by family-related variables.

PMID- 25393730
TI  - Mammalian target of rapamycin complex 2 signaling pathway regulates transient
      receptor potential cation channel 6 in podocytes.
AB  - Transient receptor potential cation channel 6 (TRPC6) is a nonselective cation
      channel, and abnormal expression and gain of function of TRPC6 are involved in
      the pathogenesis of hereditary and nonhereditary forms of renal disease. Although
      the molecular mechanisms underlying these diseases remain poorly understood,
      recent investigations revealed that many signaling pathways are involved in
      regulating TRPC6. We aimed to examine the effect of the mammalian target of
      rapamycin (mTOR) complex (mTOR complex 1 [mTORC1] or mTOR complex 2 [mTORC2])
      signaling pathways on TRPC6 in podocytes, which are highly terminally
      differentiated renal epithelial cells that are critically required for the
      maintenance of the glomerular filtration barrier. We applied both pharmacological
      inhibitors of mTOR and specific siRNAs against mTOR components to explore which
      mTOR signaling pathway is involved in the regulation of TRPC6 in podocytes. The
      podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a
      dual inhibitor of mTORC1 and mTORC2. In addition, specific siRNA-mediated
      knockdown of the mTORC1 component raptor and the mTORC2 component rictor was
      employed. The TRPC6 mRNA and protein expression levels were examined via real
      time quantitative PCR and Western blot, respectively. Additionally, fluorescence
      calcium imaging was performed to evaluate the function of TRPC6 in podocytes.
      Rapamycin displayed no effect on the TRPC6 mRNA or protein expression levels or
      TRPC6-dependent calcium influx in podocytes. However, ku0063794 down-regulated
      the TRPC6 mRNA and protein levels and suppressed TRPC6-dependent calcium influx
      in podocytes. Furthermore, knockdown of raptor did not affect TRPC6 expression or
      function, whereas rictor knockdown suppressed TRPC6 protein expression and TRPC6
      dependent calcium influx in podocytes. These findings indicate that the mTORC2
      signaling pathway regulates TRPC6 in podocytes but that the mTORC1 signaling
      pathway does not appear to exert an effect on TRPC6. 

PMID- 25393731
TI  - Assessing temporal agreement between central and local progression-free survival
      times.
AB  - In oncology clinical trials, progression-free survival (PFS), generally defined
      as the time from randomization until disease progression or death, has been a key
      endpoint to support licensing approval. In the U.S. Food and Drug Administration
      guidance for industry, May 2007, concerning the PFS as the primary or co-primary
      clinical trial endpoint, it is recommended to have tumor assessments verified by
      an independent review committee blinded to study treatments, especially in open
      label studies. It is considered reassuring about the lack of reader-evaluation
      bias if treatment effect estimates from the investigators' and independent review
      committees' evaluations agree. The agreement between these evaluations may vary
      for subjects with short or long PFS, while there exist no such statistical
      quantities that can completely account for this temporal pattern of agreements.
      Therefore, in this paper, we propose a new method to assess temporal agreement
      between two time-to-event endpoints, while the two event times are assumed to
      have a positive probability of being identical. This method measures agreement in
      terms of the two event times being identical at a given time or both being
      greater than a given time. Overall scores of agreement over a period of time are
      also proposed. We propose a maximum likelihood estimation to infer the proposed
      agreement measures using empirical data, accounting for different censoring
      mechanisms, including reader's censoring (event from one reader dependently
      censored by event from the other reader). The proposed method is demonstrated to
      perform well in small samples via extensive simulation studies and is illustrated
      through a head and neck cancer trial.

PMID- 25393732
TI  - [Treatment Strategies for Septic Arthritis of the Sternoclavicular Joint].
AB  - Septic arthritis of the sternoclavicular joint (SCJ) is a relatively rare
      disease. Due to serious complications including mediastinitis and generalised
      sepsis early diagnosis and rapid onset of treatment are mandatory. The disease
      often affects immunocompromised patients, diabetics, or patients with other
      infectious diseases. The therapeutic options range from administration of
      antibiotics to extended surgery including reconstructive procedures. Apart from
      rare situations where conservative treatment with antibiotics is sufficient,
      joint resection followed by plastic surgical procedures are required. We present
      a retrospective analysis with data from two hospitals. From January 2008 to
      December 2012 23 patients with radiographically confirmed septic arthritis of
      various aetiology were included. Fourteen (60.8 %) male, nine (39.2 %) female
      patients with an average age of 60.3 +/- 14.2 years (range: 23-88 years) with
      septic arthritis of the SCJ were treated. Seven (30.4 %) patients suffered from
      Diabetes mellitus, nine (39.1 %) had underlying diseases with a compromised
      immune system. In 14 (60.8 %) out of 23 patients a bacterial focus was detected.
      Only six (26 %) patients suffered from confined septic arthritis of the SCG, in
      17 (73,9 %) patients osteomyelitis of the adjacent sternum, and the clavicle was
      present. In addition, 15 (65.2 %) patients already suffered from mediastinitis at
      the time of diagnosis, eight (35 %) patients even from septicaemia. In
      conclusion, septic arthritis requires an active surgical treatment. Limited
      incision of the joint and debridement alone is only successful at early stages of
      the disease. The treatment concept has to include the local joint and bone
      resection as well as complications like mediastinitis. After successful treatment
      of the infection, the defect of the chest wall requires secondary reconstructive
      surgery using a pedicled pectoralis muscle flap.

PMID- 25393733
TI  - [Differential Vascular Medical Management of Visceral Artery Aneurysms in a
      Single-Centre Consecutive Patient Cohort as Part of an Ongoing Disease-Specific
      Systematic Clinical Prospective Observational Study].
AB  - AIM, PATIENTS AND METHODS: By means of a systematic single-centre prospective
      observational study, spectrum (symptomatology, frequency) and diagnostics of the
      different visceral artery aneurysm sites as well as the postinterventional course
      of the various therapeutic options used according to local finding and patient's
      clinical status as well as risk factors were analysed to contrast the different
      procedures (conservative, image-guided radiological intervention, open vascular
      surgery) in consideration of their decision-making criteria and their early
      postinterventional outcome (on the basis of complication rate, peri
      interventional morbidity and hospital lethality) including relevant references
      from the literature. RESULTS: During a time period of 14 years, 22 patients (sex
      ratio: 12 males/10 females; mean age: 54.3 [range: 22-76] years) were registered.
      Most frequently, visceral artery aneurysms occurred in the splenic artery (50 %).
      The gastroduodenal artery, the hepatic artery and the right renal artery were
      affected in each with 13.6 % (n = 3/22), the superior mesenteric artery in 9.1 %
      (n = 2/22). The majority of patients (54.5 %) were treated with image-guided
      radiological intervention, whereas in 31.8 %, the patient underwent open vascular
      surgery and 13.6 % of cases were managed with "watchful waiting". While morbidity
      was 21.1 % (n = 4/19), overall lethality was 9.1 % (n = 2/22). CONCLUSION:
      Decision-making for a specific therapeutic approach should be made (i) after
      adequate diagnostic measures (transabdominal ultrasound, MR angiography, duplex
      ultrasonography, CT-A/DSA if required), (ii) on an individual case-adapted base,
      (iii) in a vascular surgical centre, (iv) case-associated to the specific local
      finding (in particular, according to size/specific probability of rupture [cave:
      gravidity]) and (v) according to the individual risk profile using the whole
      spectrum of therapeutic options (conservative vs. interventional; image-guided
      radiological intervention [endovascular repair such as embolisation, stent or
      stent graft] vs. open vascular surgery [according to a step-up approach]; open
      vascular ligation vs. reconstruction after exclusion of the aneurysm) including
      sufficient quality assurance of the treatment results as well as control
      investigations (duplex ultrasonography; MR-A if required) in a specialised
      vascular surgical out-patient centre within appropriate time intervals.

PMID- 25393734
TI  - [Surgical History Taking and Clinical Examination: Establishing a Standardised
      System by Means of a Nation-Wide Academic Teaching Project].
AB  - Background: History taking and systematic clinical examination are central
      techniques of physicians. Medicine in general and surgery in particular
      frequently require immediate decisions and start of therapies. So far, a
      standardised surgical system for history taking and clinical examination in
      teaching has been lacking at our faculty. A consensus of all medical faculties on
      a standardised system could be a tool to improve the medical teaching and
      education at our teaching institutions. Methods: The established Anglo-Saxonian
      system of history taking and clinical examination was adapted to our own clinical
      needs. Thereafter, this system was sent out to all chairmen of general and
      visceral surgery departments in German University Hospitals asking for evaluation
      and improvements. We adapted the system according to the chairmen's comments and
      suggestions. Since winter semester 2011 this system has been integrated into the
      clinical course of history taking and examination. It is compulsory for all 5th
      semester students (first clinical year/graduate course) at the
      Universitatsmedizin Greifswald. In addition, a video was produced demonstrating
      all major techniques of clinical examination. This video is available for all
      students on a password blocked site of the World Wide Web. Results: Altogether,
      89 % of all contacted chairmen returned their comments and suggestions for
      improvements. After implementation of the new system, positive evaluations of
      students increased significantly from 63.5 to 77.0 % in general and abdominal
      surgery (p < 0.0001) and from 76.4 to 83.5 % in vascular and thoracic surgery (p
      < 0.0001). Conclusions: The presented system is a standardised tool of history
      taking and clinical examination applicable for students as well as qualified
      surgeons in daily routine work. It has been approved by the majority of the
      departments of surgery of all German university hospitals. Furthermore, it can be
      applied by other medical specialties, in particular, internal medicine.
      Furthermore, the standardisation of history taking and clinical examination can
      contribute to improve patients' safety as well as medical documentation. Also,
      the standardisation will be a sound basis for expert medical opinions in legal
      actions. Finally, it has improved the value of medical education at our medical
      faculty and could form the basis for the development of national medical
      standards.

PMID- 25393735
TI  - [Surgery Meets Nephrology: Opioid Therapy of Patients with Renal Failure].

PMID- 25393736
TI  - [Venous Aneurysms of the Lower Extremities - Clinical Significance and Therapy].
AB  - Isolated venous aneurysms are very rare. In clinical practice it is predominantly
      seen in the course of a random diagnosis to find the cause of pulmonary embolism
      or venous thrombosis. Due to an increased use of duplex scans there is also an
      increase in the number of diagnoses of venous aneurysms even if patients are
      still asymptomatic. The precise prevalence is yet unknown. The choice of
      therapeutic procedure is dependent on each individual clinic as well as the size
      and morphology (fusiform or saccular) of the aneurysm. At present, the available
      data are still insufficient. We discuss our own surgical treatment of 7 patients
      with primary aneurysms involving the vena cava, iliac vein, great saphenous vein
      junction and popliteal vein in consideration of the latest literature. 

PMID- 25393737
TI  - Cadmium exposure and incidence of diabetes mellitus--results from the Malmo Diet
      and Cancer study.
AB  - BACKGROUND: Cadmium is a pollutant with multiple adverse health effects: renal
      dysfunction, osteoporosis and fractures, cancer, and probably cardiovascular
      disease. Some studies have reported associations between cadmium and impaired
      fasting glucose and diabetes. However, this relationship is controversial and
      there is a lack of longitudinal studies. OBJECTIVES: To examine prospectively
      whether cadmium in blood is associated with incidence of diabetes mellitus.
      METHODS: The study population consists of 4585 subjects without history of
      diabetes (aged 46 to 67 years, 60% women), who participated in the Malmo Diet and
      Cancer study during 1991-1994. Blood cadmium levels were estimated from
      hematocrit and cadmium concentrations in erythrocytes. Incident cases of diabetes
      were identified from national and local diabetes registers. RESULTS: Cadmium
      concentrations in blood were not associated with blood glucose and insulin levels
      at the baseline examination. However, cadmium was positively associated with
      HbA1c in former smokers and current smokers. During a mean follow-up of 15.2 +/-
      4.2 years, 622 (299 men and 323 women) were diagnosed with new-onset of diabetes.
      The incidence of diabetes was not significantly associated with blood cadmium
      level at baseline, neither in men or women. The hazard ratio (4th vs 1st
      quartile) was 1.11 (95% confidence interval 0.82-1.49), when adjusted for
      potential confounders. CONCLUSIONS: Elevated blood cadmium levels are not
      associated with increased incidence of diabetes. The positive association between
      HbA1c and blood cadmium levels has a likely explanation in mechanisms related to
      erythrocyte turnover and smoking.

PMID- 25393738
TI  - Radial growth of two dominant montane conifer tree species in response to climate
      change in North-Central China.
AB  - North-Central China is a region in which the air temperature has clearly
      increased for several decades. Picea meyeri and Larix principis-rupprechtii are
      the most dominant co-occurring tree species within the cold coniferous forest
      belt ranging vertically from 1800 m to 2800 m a.s.l. in this region. Based on a
      tree-ring analysis of 292 increment cores sampled from 146 trees at different
      elevations, this study aimed to examine if the radial growth of the two species
      in response to climate is similar, whether the responses are consistent along
      altitudinal gradients and which species might be favored in the future driven by
      the changing climate. The results indicated the following: (1) The two species
      grew in different rhythms at low and high elevation respectively; (2) Both
      species displayed inconsistent relationships between radial growth and climate
      data along altitudinal gradients. The correlation between radial growth and the
      monthly mean temperature in the spring or summer changed from negative at low
      elevation into positive at high elevation, whereas those between the radial
      growth and the total monthly precipitation displayed a change from positive into
      negative along the elevation gradient. These indicate the different influences of
      the horizontal climate and vertical mountainous climate on the radial growth of
      the two species; (3) The species-dependent different response to climate in
      radial growth appeared mainly in autumn of the previous year. The radial growth
      of L. principis-rupprechtii displayed negative responses both to temperature and
      to precipitation in the previous September, October or November, which was not
      observed in the radial growth of P. meyeri. (4) The radial growth of both species
      will tend to be increased at high elevation and limited at low elevation, and L.
      principis-rupprechtii might be more favored in the future, if the temperature
      keeps rising. 

PMID- 25393739
TI  - In silico design and biological evaluation of a dual specificity kinase inhibitor
      targeting cell cycle progression and angiogenesis.
AB  - BACKGROUND: Protein kinases play a central role in tumor progression, regulating
      fundamental processes such as angiogenesis, proliferation and metastasis. Such
      enzymes are an increasingly important class of drug target with small molecule
      kinase inhibitors being a major focus in drug development. However, balancing
      drug specificity and efficacy is problematic with off-target effects and toxicity
      issues. METHODOLOGY: We have utilized a rational in silico-based approach to
      demonstrate the design and study of a novel compound that acts as a dual
      inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin
      dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro
      angiogenic signal transduction and cell cycle progression in primary endothelial
      cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and
      CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual
      inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated
      signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic
      activity both in an endothelial-fibroblast co-culture model and a murine ex vivo
      model of angiogenesis. CONCLUSIONS: We deduce that JK-31 reduces the growth of
      both human endothelial cells and human breast cancer cells in vitro. This novel
      synthetic molecule has broad implications for development of similar multi-kinase
      inhibitors with anti-angiogenic and anti-cancer properties. In silico design is
      an attractive and innovative method to aid such drug discovery.

PMID- 25393740
TI  - Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization
      responses.
AB  - In response to hypoxia and other stress, the sympathetic (adrenergic) nervous
      system regulates arterial contractility and blood flow, partly through
      differential activities of the alpha1 (alpha1) - adrenergic receptor (AR)
      subtypes (alpha1A-, alpha1B-, and alpha1D-AR). Thus, we tested the hypothesis
      that with acclimatization to long-term hypoxia (LTH), contractility of middle
      cerebral arteries (MCA) is regulated by changes in expression and activation of
      the specific alpha1-AR subtypes. We conducted experiments in MCA from adult
      normoxic sheep maintained near sea level (300 m) and those exposed to LTH (110
      days at 3801 m). Following acclimatization to LTH, ovine MCA showed a 20%
      reduction (n = 5; P<0.05) in the maximum tension achieved by 10-5 M phenylephrine
      (PHE). LTH-acclimatized cerebral arteries also demonstrated a statistically
      significant (P<0.05) inhibition of PHE-induced contractility in the presence of
      specific alpha1-AR subtype antagonists. Importantly, compared to normoxic
      vessels, there was significantly greater (P<0.05) alpha1B-AR subtype mRNA and
      protein levels in LTH acclimatized MCA. Also, our results demonstrate that
      extracellular regulated kinase 1 and 2 (ERK1/2)-mediated negative feedback
      regulation of PHE-induced contractility is modulated by alpha1B-AR subtype.
      Overall, in ovine MCA, LTH produces profound effects on alpha1-AR subtype
      expression and function. 

PMID- 25393741
TI  - Evolution of Early Repolarization Patterns after 5 Years in a Military Population
      at Low Cardiovascular Risk and Practical Implications in Military Medical
      Expertise.
AB  - BACKGROUND: The French military population is a young and athletic population
      with a high prevalence of early repolarization patterns (ERP) compared to the
      general population. Screening of military officers at risk of sudden death (SD)
      is a priority in military medical expertise. The aim of our study was to evaluate
      the prevalence of ERP and its evolution over a period of 5 years in a specific
      asymptomatic population, free of heart disease and cardiovascular risk factors.
      METHODS: From March to December 2008, we prospectively collected the
      electrocardiograms (ECGs) of military officers enlisted into the submarine forces
      of France. For 5 years (until 2012), the military officers included in the study
      underwent a clinical examination twice per year. A new ECG was carried out 5
      years after the initial one. RESULTS: A total of 250 male subjects were included
      (mean age 22.87 +/- 0.5 years). The prevalence of ERP was 19.2%. The most common
      appearance was an elevation of a slurring type J point (31/48 or 64.5%) in
      inferolateral leads (18/48 or 37.8%). After 5 years, the prevalence of ERP was
      identical to that of the previous period (19.2%) with no change in appearance,
      distribution, and amplitude in 47 subjects (97.9%). Repolarization changed in two
      patients (one occurrence of ERP and one disappearance). During the 5 years of
      follow-up, the subjects remained asymptomatic CONCLUSION: ERP is common in our
      population of young, athletic, and asymptomatic military officers and changes
      little in 5 years.

PMID- 25393744
TI  - AgF-mediated fluorinative cross-coupling of two olefins: facile access to alpha
      CF3 alkenes and beta-CF3 ketones.
AB  - A AgF-mediated fluorination with a concomitant cross-coupling between a gem
      difluoroolefin and a non-fluorinated olefin is reported. This highly efficient
      method provides facile access to both alpha-CF3 alkenes and beta-CF3 ketones,
      which otherwise remain challenging to be directly prepared. The application of
      this method is further demonstrated by the synthesis of bioactive isoxazoline
      derivatives. This approach represents a conceptually novel route to
      trifluoromethylated compounds that combines the in situ generation of the CF3
      moiety and a C-H functionalization in a single reaction system.

PMID- 25393745
TI  - Tracking youth self-inflicted injury hospitalizations to target high-risk
      communities, leverage resources, and unify stakeholder efforts: Illinois
      Department of Public Health.

PMID- 25393742
TI  - The plasmodesmal protein PDLP1 localises to haustoria-associated membranes during
      downy mildew infection and regulates callose deposition.
AB  - The downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa) is a filamentous
      oomycete that invades plant cells via sophisticated but poorly understood
      structures called haustoria. Haustoria are separated from the host cell cytoplasm
      and surrounded by an extrahaustorial membrane (EHM) of unknown origin. In some
      interactions, including Hpa-Arabidopsis, haustoria are progressively encased by
      host-derived, callose-rich materials but the molecular mechanisms by which
      callose accumulates around haustoria remain unclear. Here, we report that
      PLASMODESMATA-LOCATED PROTEIN 1 (PDLP1) is expressed at high levels in Hpa
      infected cells. Unlike other plasma membrane proteins, which are often excluded
      from the EHM, PDLP1 is located at the EHM in Hpa-infected cells prior to
      encasement. The transmembrane domain and cytoplasmic tail of PDLP1 are sufficient
      to convey this localization. PDLP1 also associates with the developing encasement
      but this association is lost when encasements are fully mature. We found that the
      pdlp1,2,3 triple mutant is more susceptible to Hpa while overexpression of PDLP1
      enhances plant resistance, suggesting that PDLPs enhance basal immunity against
      Hpa. Haustorial encasements are depleted in callose in pdlp1,2,3 mutant plants
      whereas PDLP1 over-expression elevates callose deposition around haustoria and
      across the cell surface. These data indicate that PDLPs contribute to callose
      encasement of Hpa haustoria and suggests that the deposition of callose at
      haustoria may involve similar mechanisms to callose deposition at plasmodesmata. 

PMID- 25393746
TI  - Trends in diabetes and cardiometabolic conditions in a Canadian First Nation
      community, 2002-2003 to 2011-2012.
AB  - INTRODUCTION: The burden of diabetes and cardiovascular disease among the
      Canadian First Nation population is disproportionately high compared with the
      general Canadian population. Continuous monitoring of the diabetes epidemic among
      the Canadian First Nations population is necessary to inform public health
      practice. The purpose of the study was to compare the prevalence of diabetes and
      cardiometabolic conditions in a Manitoba First Nation between 2 periods. METHODS:
      Study data were from 2 diabetes screening studies in Sandy Bay Ojibway First
      Nation in Manitoba, collected in 2002-2003 and 2011-2012. All adults aged 18
      years or older were invited to participate in both studies. Crude and sex- and
      age-standardized prevalence of diabetes and cardiometabolic conditions for each
      period were estimated and compared with each other by using chi(2) tests.
      RESULTS: Sex- and age-standardized prevalence of diabetes was estimated at 39.4%
      (95% confidence interval [CI], 35.1-43.8) in 2002-2003 and was not significantly
      different (P = .99) in 2011-2012. Sex- and age-standardized obesity prevalence
      was significantly lower in 2011-2012, at 48.7% (95% CI, 44.6-52.7), compared with
      60.8% (95% CI, 56.4-65.2) in 2002-2003 (P < .001). However, this finding was
      accounted for by a lower prevalence of obesity among men aged 40 to 49 and aged
      50 years or older in 2011-2012 compared with 2002-2003. Sex- and age-standardized
      prevalence of hypertension (P = .97), abdominal obesity (P = .26), dyslipidemia
      (P = .73), and metabolic syndrome (P = .67) were not significantly different
      between periods. Significantly higher crude prevalence of obesity, abdominal
      obesity, dyslipidemia, and metabolic syndrome among women compared with men
      persisted from 2002-2003 to 2011-2012. CONCLUSION: The diabetes epidemic remains
      a serious problem in this First Nation community. The gap in cardiometabolic
      burden between men and women has also persisted.

PMID- 25393747
TI  - Impact of the Arthritis Foundation's Walk With Ease Program on arthritis symptoms
      in African Americans.
AB  - INTRODUCTION: Inadequate program design and lack of access to evidence-based
      programs are major barriers to the management of chronic diseases such as
      arthritis, particularly for African Americans. This study evaluates the
      effectiveness of the Arthritis Foundation's Walk With Ease Program (WWE) in a
      subsample of African Americans who were part of a larger study that established
      evidence of the program's efficacy. METHODS: Participants were African Americans
      (N = 117) with self-reported arthritis who chose to participate in either a self
      directed (n = 68) or group (n = 49) 6-week WWE program. Arthritis-related
      symptoms (ie, pain, fatigue, stiffness; measured using visual analog scales) were
      assessed at baseline, 6 weeks, and 1 year. Independent samples t tests were
      conducted to examine group differences (ie, self-directed vs group) in arthritis
      related symptoms at baseline, and paired sample t tests were conducted to examine
      differences over time (ie, baseline to 6 weeks and baseline to 1 year) in
      symptoms. Satisfaction was examined by descriptive statistics. RESULTS: Younger,
      more educated individuals chose the self-directed format (P < .001, P = .008;
      respectively). After the 6-week intervention, participants reported a decrease in
      pain (P < .001), fatigue (P = .002), and stiffness (P < .001). At 1 year, the
      decrease in pain (P = .04) and stiffness (P = .002) remained constant. Overall,
      participants were satisfied with both program formats. CONCLUSION: The
      individualized and group formats of the WWE program improved arthritis-related
      pain, fatigue, and stiffness in African Americans. Culturally appealing arthritis
      interventions ultimately may increase the use of existing arthritis
      interventions.

PMID- 25393748
TI  - Testing for human immunodeficiency virus among cancer survivors under age 65 in
      the United States.
AB  - INTRODUCTION: Knowing the human immunodeficiency virus (HIV) serostatus of
      patients at the time of cancer diagnosis or cancer recurrence is prerequisite to
      coordinating HIV and cancer treatments and improving treatment outcomes. However,
      there are no published data about HIV testing among cancer survivors in the
      United States. We sought to provide estimates of the proportion of cancer
      survivors tested for HIV and to characterize factors associated with having had
      HIV testing. METHODS: We used data from the 2009 Behavioral Risk Factor
      Surveillance System to calculate the proportion of cancer survivors under age 65
      who had undergone HIV testing, by demographic and health-related factors and by
      state. Adjusted proportion estimates were calculated by multivariable logistic
      regression. RESULTS: Only 41% of cancer survivors in the United States under the
      age of 65 reported ever having had an HIV test. The highest proportion of
      survivors tested was among patients aged 25 to 34 years (72.2%), non-Hispanic
      blacks (59.5%), and cervical cancer survivors (51.2%). The proportion tested was
      highest in the District of Columbia (68.3%) and lowest in Nebraska (24.1%).
      Multivariable analysis showed that factors associated with HIV testing included
      being non-Hispanic black or Hispanic, being younger, having higher education, not
      being married or living with a partner, not being disabled, and having medical
      cost concerns. Having an AIDS-related cancer was associated with HIV testing only
      among females. CONCLUSION: The proportions of HIV testing varied substantially by
      demographic and health-related factors and by state. Our study points to the need
      for public health interventions to promote HIV testing among cancer survivors.

PMID- 25393749
TI  - Evolution in obesity and chronic disease prevention practice in California public
      health departments, 2010.
AB  - INTRODUCTION: Local health departments (LHDs) are dedicating resources and
      attention to preventing obesity and associated chronic diseases, thus expanding
      their work beyond traditional public health activities such as surveillance. This
      study investigated practices of local health departments in California to prevent
      obesity and chronic disease. METHODS: We conducted a web-based survey in 2010
      with leaders in California's LHDs to obtain diverse perspectives on LHDs'
      practices to prevent obesity and chronic disease. The departmental response rate
      for the 2010 survey was 87% (53 of California's 61 LHDs). RESULTS: Although staff
      for preventing obesity and chronic disease decreased at 59% of LHDs and stayed
      the same at 26% of LHDs since 2006, LHDs still contributed the same (12%) or a
      higher (62%) level of effort in these areas. Factors contributing to internal
      changes to address obesity and chronic disease prevention included momentum in
      the field of obesity prevention, opportunities to learn from other health
      departments, participation in obesity and chronic disease prevention initiatives,
      and flexible funding streams for chronic disease prevention. LHDs that received
      foundation funding or had a lead person or organizational unit coordinating or
      taking the lead on activities related to obesity and chronic disease prevention
      were more likely than other LHDs to engage in some activities related to obesity
      prevention. CONCLUSION: California LHDs are increasing the intensity and breadth
      of obesity and chronic disease prevention. Findings provide a benchmark from
      which further changes in the activities and funding sources of LHD chronic
      disease prevention practice may be measured.

PMID- 25393750
TI  - Laverne K. Eveland--a compassionate person, and a scientist with humility (1940
      2014).

PMID- 25393755
TI  - Spectral-domain-optical coherence tomography in uveitis.

PMID- 25393756
TI  - High-definition optical coherence tomography findings in acute idiopathic blind
      spot enlargement (AIBSE) syndrome.

PMID- 25393751
TI  - Dynamics on networks: the role of local dynamics and global networks on the
      emergence of hypersynchronous neural activity.
AB  - Graph theory has evolved into a useful tool for studying complex brain networks
      inferred from a variety of measures of neural activity, including fMRI, DTI, MEG
      and EEG. In the study of neurological disorders, recent work has discovered
      differences in the structure of graphs inferred from patient and control cohorts.
      However, most of these studies pursue a purely observational approach;
      identifying correlations between properties of graphs and the cohort which they
      describe, without consideration of the underlying mechanisms. To move beyond this
      necessitates the development of computational modeling approaches to
      appropriately interpret network interactions and the alterations in brain
      dynamics they permit, which in the field of complexity sciences is known as
      dynamics on networks. In this study we describe the development and application
      of this framework using modular networks of Kuramoto oscillators. We use this
      framework to understand functional networks inferred from resting state EEG
      recordings of a cohort of 35 adults with heterogeneous idiopathic generalized
      epilepsies and 40 healthy adult controls. Taking emergent synchrony across the
      global network as a proxy for seizures, our study finds that the critical
      strength of coupling required to synchronize the global network is significantly
      decreased for the epilepsy cohort for functional networks inferred from both
      theta (3-6 Hz) and low-alpha (6-9 Hz) bands. We further identify left frontal
      regions as a potential driver of seizure activity within these networks. We also
      explore the ability of our method to identify individuals with epilepsy,
      observing up to 80% predictive power through use of receiver operating
      characteristic analysis. Collectively these findings demonstrate that a computer
      model based analysis of routine clinical EEG provides significant additional
      information beyond standard clinical interpretation, which should ultimately
      enable a more appropriate mechanistic stratification of people with epilepsy
      leading to improved diagnostics and therapeutics.

PMID- 25393757
TI  - Multiply bonded metal(II) acetate (rhodium, ruthenium, and molybdenum) complexes
      with the trans-1,2-bis(N-methylimidazol-2-yl)ethylene ligand.
AB  - The synthesis and structural characterization of new coordination polymers with
      the N,N-donor ligand trans-1,2-bis(N-methylimidazol-2-yl)ethylene (trans-bie) are
      reported. It was found that the acetate-bridged paddlewheel metal(II) complexes
      [M2(O2CCH3)4(trans-bie)]n with M = Rh, Ru, Mo, and Cr are linked by the trans-bie
      ligand to give a one-dimensional alternating chain. The metal-metal multiple
      bonds were analyzed with density functional theory and CASSCF/CASPT2 calculations
      (bond orders: Rh, 0.8; Ru, 1.7; Mo, 3.3). 

PMID- 25393758
TI  - Dicarba analogues of alpha-conotoxin RgIA. Structure, stability, and activity at
      potential pain targets.
AB  - alpha-Conotoxin RgIA is both an antagonist of the alpha9alpha10 nicotinic
      acetylcholine receptor (nAChR) subtype and an inhibitor of high-voltage-activated
      N-type calcium channel currents. RgIA has therapeutic potential for the treatment
      of pain, but reduction of the disulfide bond framework under physiological
      conditions represents a potential liability for clinical applications. We
      synthesized four RgIA analogues that replaced native disulfide pairs with
      nonreducible dicarba bridges. Solution structures were determined by NMR,
      activity assessed against biological targets, and stability evaluated in human
      serum. [3,12]-Dicarba analogues retained inhibition of ACh-evoked currents at
      alpha9alpha10 nAChRs but not N-type calcium channel currents, whereas [2,8]
      dicarba analogues displayed the opposite pattern of selectivity. The [2,8]
      dicarba RgIA analogues were effective in HEK293 cells stably expressing human
      Cav2.2 channels and transfected with human GABAB receptors. The analogues also
      exhibited improved serum stability over the native peptide. These selectively
      acting dicarba analogues may represent mechanistic probes to explore analgesia
      related biological receptors. 

PMID- 25393759
TI  - The multitentaculate Cirratulidae of the genera Cirriformia and Timarete
      (Annelida: Polychaeta) from shallow waters of Brazil.
AB  - A large number multitentaculate cirratulids have been described worldwide but
      most are only known through the original descriptions. Type material, voucher and
      recently collected specimens from Brazil were revisited in order to reveal their
      true identity and confirm the records of widely distributed species in this
      region. Six species are described, three of which are new, Cirriformia
      capixabensis sp. nov., Cirriformia chicoi sp. nov. and Timarete ceciliae sp. nov.
      COI and 16S sequences were obtained and used for inter-specific comparisons.
      Timarete caribous is reported from several localities along the Brazilian coast
      and a new synonym, Cirratulus melanacanthus, is proposed. The species Timarete
      oculata, originally described from Brazil and lumped into the Timarete filigera
      species complex, is herein revalidated and redescribed. The occurrence of the
      species Timarete filigera and Cirriformia tentaculata is not confirmed from the
      Brazilian coast. Descriptions, illustrations and a key to genera and species are
      provided. 

PMID- 25393760
TI  - A method for estimating radiation interaction coefficients for tissues from
      single energy CT.
AB  - A parametric model for the x-ray linear attenuation coefficient is used to
      describe the compositional dependence of Hounsfield numbers measured by medical
      CT scanners. Measurements with materials of known density and composition, that
      span and evenly sample the compositional range of tissues, are written as linear
      simultaneous equations and solved for model coefficients. An algorithm is
      identified for this purpose. Results are expressed as atomic cross-sections in
      units of barn per electron divided by the attenuation coefficient for water. With
      the CT scanner characterised, a virtual CT scan can be simulated to predict HN
      for tissues based upon their known density and composition. Similar calculations
      using the tabulations and mixture rule deliver attenuation coefficients and mass
      energy absorption coefficients for mono-energetic radiation 10 keV to 20 MeV.
      Results are presented for measurements with a radiotherapy CT simulator, the RMI
      467 phantom with tissue substitute materials, plus common polymer materials and
      silicon. Published measurements with earlier generations of the phantom and
      tissue substitutes using different CT scanners are also considered. Measured
      atomic cross-sections differ from expectations for mono-energetic radiation due
      to the use of a filtered spectrum and energy integrating detection system. The
      cross-sections for different CT scanners are similar, without large variations
      with kVp. Results are presented showing the relationship between predicted HN for
      tissues, electron density and photon interaction coefficients for healthy tissues
      and mono-energetic radiation. A strategy is suggested for accommodating strongly
      attenuating materials such as calculi and metallic implants.

PMID- 25393761
TI  - Synthesis and characterization of 12-pyridinium derivatives of the [closo-1
      CB11H12]- anion.
AB  - Diazotization of [closo-1-CB11H10-1-R-12-NH2](-)[NMe4](+) (4[NMe4]) in neat 4
      methoxypyridine leads to 12-(4-methoxypyridinium) zwitterions [closo-1-CB11H10-1
      R-12-(4-MeOC5H4N)] (2) in ~50% yield. Demethylation of 2 with LiCl in
      dimethylformamide provides access to 12-pyridones 5[NMe4], which can be O
      alkylated with alkyl triflates giving 12-(4-alkoxypyridinium) zwitterions, such
      as 1. This three-step process is more efficient than direct diazotization of
      amine 4[NMe4] in neat higher 4-alkoxypyridine. The new method was demonstrated
      for the synthesis of [closo-1-CB11H10-1-C5H11-12-(4-C7H15OC5H4N)] (1c), which
      exhibits a smectic A phase. Molecular and electronic structures of 4
      methoxypyridinium zwitterion 2b and its C(1) isomer [closo-1-CB11H11-1-(4
      MeOC5H4N)] (3b) were investigated by single-crystal X-ray diffraction and
      spectroscopic methods, respectively, and the experimental results were compared
      to those obtained with density functional theory methods. Lastly, the mechanism
      for formation of zwitterions 2 was investigated computationally revealing low
      energy for dediazoniation of the [closo-1-CB11H10-1-R-12-N2] (14) intermediate
      (DeltaG298 ~ 25 kcal/mol) to form boronium ylide 15, with weak dependence on
      substituent R. Dinitrogen derivative 14c was observed by (11)B NMR spectroscopy. 

PMID- 25393762
TI  - The red queen model of recombination hotspots evolution in the light of archaic
      and modern human genomes.
AB  - Recombination is an essential process in eukaryotes, which increases diversity by
      disrupting genetic linkage between loci and ensures the proper segregation of
      chromosomes during meiosis. In the human genome, recombination events are
      clustered in hotspots, whose location is determined by the PRDM9 protein. There
      is evidence that the location of hotspots evolves rapidly, as a consequence of
      changes in PRDM9 DNA-binding domain. However, the reasons for these changes and
      the rate at which they occur are not known. In this study, we investigated the
      evolution of human hotspot loci and of PRDM9 target motifs, both in modern and
      archaic human lineages (Denisovan) to quantify the dynamic of hotspot turnover
      during the recent period of human evolution. We show that present-day human
      hotspots are young: they have been active only during the last 10% of the time
      since the divergence from chimpanzee, starting to be operating shortly before the
      split between Denisovans and modern humans. Surprisingly, however, our analyses
      indicate that Denisovan recombination hotspots did not overlap with modern human
      ones, despite sharing similar PRDM9 target motifs. We further show that high
      affinity PRDM9 target motifs are subject to a strong self-destructive drive,
      known as biased gene conversion (BGC), which should lead to the loss of the
      majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is
      expected to decrease fitness, and thereby to favor new PRDM9 alleles binding
      different motifs. Our refined estimates of the age and life expectancy of human
      hotspots provide empirical evidence in support of the Red Queen hypothesis of
      recombination hotspots evolution.

PMID- 25393763
TI  - In vitro evolution and affinity-maturation with Coliphage qbeta display.
AB  - The Escherichia coli bacteriophage, Qbeta (Coliphage Qbeta), offers a favorable
      alternative to M13 for in vitro evolution of displayed peptides and proteins due
      to high mutagenesis rates in Qbeta RNA replication that better simulate the
      affinity maturation processes of the immune response. We describe a benchtop in
      vitro evolution system using Qbeta display of the VP1 G-H loop peptide of foot
      and-mouth disease virus (FMDV). DNA encoding the G-H loop was fused to the A1
      minor coat protein of Qbeta resulting in a replication-competent hybrid phage
      that efficiently displayed the FMDV peptide. The surface-localized FMDV VP1 G-H
      loop cross-reacted with the anti-FMDV monoclonal antibody (mAb) SD6 and was found
      to decorate the corners of the Qbeta icosahedral shell by electron microscopy.
      Evolution of Qbeta-displayed peptides, starting from fully degenerate coding
      sequences corresponding to the immunodominant region of VP1, allowed rapid in
      vitro affinity maturation to SD6 mAb. Qbeta selected under evolutionary pressure
      revealed a non-canonical, but essential epitope for mAb SD6 recognition
      consisting of an Arg-Gly tandem pair. Finally, the selected hybrid phages induced
      polyclonal antibodies in guinea pigs with good affinity to both FMDV and hybrid
      Qbeta-G-H loop, validating the requirement of the tandem pair epitope. Qbeta
      display emerges as a novel framework for rapid in vitro evolution with affinity
      maturation to molecular targets. 

PMID- 25393764
TI  - Familial Mediterranean fever associated with MEFV mutations in a large cohort of
      Cypriot patients.
AB  - Familial Mediterranean fever (FMF) is caused by mutations in the MEFV gene and
      the spectrum of mutations among Greek-Cypriots with FMF-related symptoms was
      examined. Sequence analysis for exons 2, 3, 5, and 10 of the MEFV gene was
      performed in a cohort of 593 patients. A total of 70 patients carried mutations
      in the homozygote or compound heterozygote state, 128 were identified with one
      MEFV mutation and 395 had no mutations. Of the 268 identified alleles,
      p.Val726Ala (27.61%) was the most frequent followed by p.Met694Val (19.40%). The
      missense mutations p.Arg761His (3.73%) and p.Ala744Ser (2.24%) were identified as
      the rarest. An interesting finding is the high frequency (18.28%) of the complex
      p.Phe479Leu-p.Glu167Asp that was identified in 49 of the mutated alleles. The
      MEFV genotypes did not follow a binomial distribution and proved not to satisfy
      the HWE (P < 0.001). The high percentage (66.61%) of patients with unidentified
      mutations could be due to mutations in the rest of the coding or noncoding MEFV
      gene or due to mutations in other genes that are also causing Hereditary
      Recurrent Fevers. Results from this work indicate the high incidence of FMF in
      Cyprus and describe the spectrum of the mutations which occur in the country. 

PMID- 25393765
TI  - Progranulin facilitates conversion and function of regulatory T cells under
      inflammatory conditions.
AB  - The progranulin (PGRN) is known to protect regulatory T cells (Tregs) from a
      negative regulation by TNF-alpha, and its levels are elevated in various kinds of
      autoimmune diseases. Whether PGRN directly regulates the conversion of CD4+CD25-T
      cells into Foxp3-expressing regulatory T cells (iTreg), and whether PGRN affects
      the immunosuppressive function of Tregs, however, remain unknown. In this study
      we provide evidences demonstrating that PGRN is able to stimulate the conversion
      of CD4+CD25-T cells into iTreg in a dose-dependent manner in vitro. In addition,
      PGRN showed synergistic effects with TGF-beta1 on the induction of iTreg. PGRN
      was required for the immunosuppressive function of Tregs, since PGRN-deficient
      Tregs have a significant decreased ability to suppress the proliferation of
      effector T cells (Teff). In addition, PGRN deficiency caused a marked reduction
      in Tregs number in the course of inflammatory arthritis, although no significant
      difference was observed in the numbers of Tregs between wild type and PGRN
      deficient mice during development. Furthermore, PGRN deficiency led to
      significant upregulation of the Wnt receptor gene Fzd2. Collectively, this study
      reveals that PGRN directly regulates the numbers and function of Tregs under
      inflammatory conditions, and provides new insight into the immune regulatory
      mechanism of PGRN in the pathogenesis of inflammatory and immune-related
      diseases. 

PMID- 25393767
TI  - Molecularly imprinted protein recognition cavities bearing exchangeable binding
      sites for postimprinting site-directed introduction of reporter molecules for
      readout of binding events.
AB  - Protein-imprinted cavities bearing exchangeable domains to be used for
      postimprinting fluorophore introduction to transform binding events into
      fluorescence changes were constructed in molecularly imprinted polymer (MIPs)
      matrixes prepared on glass substrates. Copolymerization was performed with
      acrylamide, N,N'-methylenebisaclylamide, and a newly designed functional group
      exchangeable monomer, ({[2-(2
      methacrylamido)ethyldithio]ethylcarbamoyl}methoxy)acetic acid (MDTA), in the
      presence of a model basic protein, lysozyme (Lyso); MDTA can interact with Lyso
      and assemble close to Lyso in the resulting polymer. After removal of Lyso,
      followed by a disulfide reduction to cleave the (ethylcarbamoylmethoxy)acetic
      acid moiety from the MDTA residues, the exposed thiol groups within the imprinted
      cavities were modified by aminoethylpyridyldisulfide to be transformed into
      aminoethyl groups that function as active sites for amine-reactive fluorophores.
      Fluorescein isothiocyanate (FITC) was then coupled with the aminoethyl groups,
      yielding site specifically FITC-modified signaling imprinted cavities for Lyso
      binding. Because the in-cavity fluorescent labeling was achieved via a disulfide
      linkage, it was easy to remove, exchange, and/or replace amine-reactive
      fluorophores. This facilitated the screening of fluorophores to select the
      highest readout for binding events, replace fluorophores when photobleaching
      occurred, and introduce other functions. The proposed molecular imprinting
      process, combined with postimprinting modifications, is expected to provide an
      affordable route to develop multifunctional MIPs for specific detection of
      protein binding events. 

PMID- 25393766
TI  - Biocompatible infinite-coordination-polymer nanoparticle-nucleic-acid conjugates
      for antisense gene regulation.
AB  - Herein, we report the synthesis of DNA-functionalized infinite-coordination
      polymer (ICP) nanoparticles as biocompatible gene-regulation agents. ICP
      nanoparticles were synthesized from ferric nitrate and a ditopic 3-hydroxy-4
      pyridinone (HOPO) ligand bearing a pendant azide. Addition of Fe(III) to a
      solution of the ligand produced nanoparticles, which were colloidally unstable in
      the presence of salts. Conjugation of DNA to the Fe(III)-HOPO ICP particles by
      copper-free click chemistry afforded colloidally stable nucleic-acid
      nanoconstructs. The DNA-ICP particles, when cross-linked through sequence
      specific hybridization, exhibited narrow, highly cooperative melting transitions
      consistent with dense DNA surface loading. The ability of the DNA-ICP particles
      to enter cells and alter protein expression was also evaluated. Our results
      indicate that these novel particles carry nucleic acids into mammalian cells
      without the need for transfection agents and are capable of efficient gene
      knockdown.

PMID- 25393768
TI  - Low-SES children's eyewitness memory: the effects of verbal labels and vocabulary
      skills.
AB  - This study examined the effects of the verbal labels procedure and vocabulary
      skills on low-socioeconomic status (SES) preschool children's eyewitness memory.
      Children (N = 176) aged 3-5 years witnessed a conflict event and were then
      questioned about it in either a standard or a verbal labels interview. Findings
      revealed that children with higher rather than lower vocabulary skills produced
      more complete and accurate memories. Children who were given the verbal labels
      interview recalled more information, which included both correct and incorrect
      details. Overall, the verbal labels procedure did not improve children's
      performance on direct questions, but children with low vocabulary skills answered
      direct questions more accurately if they were given the verbal labels interview
      than when they were not. Implications of the findings for memory performance of
      low-SES children are discussed.

PMID- 25393769
TI  - Oxygen isotope fractionation in double carbonates.
AB  - Oxygen isotope fractionations in double carbonates of different crystal
      structures were calculated by the increment method. Synthesis experiments were
      performed at 60  degrees C and 100  degrees C to determine oxygen and carbon
      isotope fractionations involving PbMg[CO3]2. The calculations suggest that the
      double carbonates of calcite structure are systematically enriched in (18)O
      relative to those of aragonite and mixture structures. Internally consistent
      oxygen isotope fractionation factors are obtained for these minerals with respect
      to quartz, calcite and water at a temperature range of 0-1200  degrees C. The
      calculated fractionation factors for double carbonate-water systems are generally
      consistent with the data available from laboratory experiments. The
      experimentally determined fractionation factors for PbMg[CO3]2, BaMg[CO3]2 and
      CaMg[CO3]2 against H2O not only fall between fractionation factors involving pure
      carbonate end-members but are also close to the calculated fractionation factors.
      In contrast, experimentally determined carbon isotope fractionation factors
      between PbMg[CO3]2 and CO2 are much closer to theoretical predictions for the
      cerussite-CO2 system than for the magnesite-CO2 system, similar to the
      fractionation behavior for BaMg[CO3]2. Therefore, the combined theoretical and
      experimental results provide insights into the effects of crystal structure and
      exchange kinetics on oxygen isotope partitioning in double carbonates.

PMID- 25393770
TI  - Heritability of racing performance in the Australian Thoroughbred racing
      population.
AB  - Performance data for 164,046 Thoroughbreds entered in a race or official barrier
      trial in Australia were provided by Racing Information Services Australia.
      Analyses estimating the heritability for a range of racing performance traits
      using a single-trait animal model were performed using ASREML-R. Log of
      cumulative earnings (LCE; 0.19 +/- 0.01), log of earnings per race start (0.23 +/
      0.02) and best race distance (0.61 +/- 0.03) were all significantly heritable.
      Fixed effects for sex were significant (P < 0.001) for all performance traits
      aside from LCE (P = 0.382). With the exception of annual earnings, trainer was
      also significant for all performance traits. As the application of modern genetic
      selection methodologies continues to gain popularity in the racing industry,
      contemporary heritability estimates from the current population of Thoroughbreds
      will play a vital role in identifying which traits are better suited to selection
      and in the development of more accurate genomic evaluations for racing
      performance.

PMID- 25393771
TI  - Computational survey of sequence specificity for protein terminal tags covering
      nine organisms and its application to protein identification.
AB  - In 1998, Wilkins et al. (J. Mol. Biol. 1998, 278, 599-608) reported high
      specificity in terminal regions (terminal tags) of 15 519 proteins from five
      organisms and proposed a methodology for identifying proteins by terminal tags.
      However, their examined sequence data were not based on complete genome
      sequences. Here, we examined current proteome data (217 249 entries from UniProt
      2013_6 complete/reference proteome for nine organisms including human) in terms
      of the specificity of terminal tags and their computational annotation. One
      example from the results indicated that the specificity of N-terminal tags
      plateaued at 28% at a length of six residues for human; even when using both N-
      and C-terminal tags, specificity was merely 66%. In order to determine the cause
      of these low specificities, the annotation of proteins sharing terminal tags with
      other proteins was examined. The results suggested that a large majority were
      phylogenetically or functionally related, whereas nonrelated proteins sharing
      terminal tags made up less than 1% of human proteome data. On the basis of these
      findings, we constructed the terminal tag sequence database ProteinCarta
      (http://ms3d.jp/software/proteincarta/), which includes all terminal tags of
      proteomes from the nine organisms analyzed here, in order to confirm the
      specificity of terminal tags and to identify the parent protein.

PMID- 25393773
TI  - The diagnostic performance of cardiac magnetic resonance in detection of
      myocardial involvement in AL amyloidosis.
AB  - BACKGROUND: The non-invasive assessment of amyloid heart disease may be
      challenging. Cardiac magnetic resonance (CMR) represents a method of choice for
      assessment of left ventricular (LV) morphology and function, and it also provides
      a unique possibility to evaluate the presence of amyloid deposition by the late
      gadolinium enhancement (LGE) technique. However, so far, published studies have
      not been consistent in terms of described LGE patterns associated with amyloid
      cardiomyopathy. AIMS: To compare echocardiographic and CMR assessment of LV
      morphology and function and to evaluate the presence and pattern of LGE in a
      population of patients with AL amyloid cardiomyopathy. METHODS: Twenty-two
      consecutive patients with newly diagnosed AL amyloid cardiomyopathy and without
      contraindications to CMR were comprehensively examined by echocardiography and
      CMR. RESULTS: Echocardiography and CMR did not differ in the evaluation of
      interventricular septal thickness, LV end-diastolic diameter and ejection
      fraction. Significant differences were found between echocardiographic and CMR
      estimates of LV end-diastolic volume (P<0.01) and LV mass (P<0.001). Various
      global LGE patterns (transmural homogenous or heterogeneous, subendocardial) were
      present in 17 patients (77%), patchy LGE was observed in one case (4.5%) and
      suboptimal nulling of the myocardium was reported in two subjects (9%).
      CONCLUSIONS: Echocardiography significantly overestimates LV mass and
      underestimates LV volumes in patients with AL amyloid cardiomyopathy as compared
      to CMR. As it is present in more than three quarters of individuals with AL
      amyloid cardiomyopathy, any type of global LGE pattern may be considered as
      pathogenomic for amyloid heart disease.

PMID- 25393772
TI  - Effects of storage-aged red blood cell transfusions on endothelial function in
      hospitalized patients.
AB  - BACKGROUND: Clinical and animal studies indicate that transfusions of older
      stored red blood cells (RBCs) impair clinical outcomes as compared to fresh RBC
      transfusions. It has been suggested that this effect is due to inhibition of
      nitric oxide (NO)-mediated vasodilation after transfusion of older RBC units.
      However, to date this effect has not been identified in human transfusion
      recipients. STUDY DESIGN AND METHODS: Forty-three hospitalized patients with
      transfusion orders were randomly assigned to receive either fresh (<14 days) or
      older stored (>21 days) RBC units. Before transfusion, and at selected time
      points after the start of transfusion, endothelial function was assessed using
      noninvasive flow-mediated dilation assays. RESULTS: After transfusion of older
      RBC units, there was a significant reduction in NO-mediated vasodilation at 24
      hours after transfusion (p = 0.045), while fresh RBC transfusions had no effect
      (p = 0.231). CONCLUSIONS: This study suggests for the first time a significant
      inhibitory effect of transfused RBC units stored more than 21 days on NO-mediated
      vasodilation in anemic hospitalized patients. This finding lends further support
      to the hypothesis that deranged NO signaling mediates adverse clinical effects of
      older RBC transfusions. Future investigations will be necessary to address
      possible confounding factors and confirm these results.

PMID- 25393774
TI  - Sweating chloride bullets: understanding the role of calcium in eccrine sweat
      glands and possible implications for hyperhidrosis.

PMID- 25393775
TI  - Fluctuations in nucleus accumbens extracellular glutamate and glucose during
      motivated glucose-drinking behavior: dissecting the neurochemistry of reward.
AB  - While motivated behavior involves multiple neurochemical systems, few studies
      have focused on the role of glutamate, the brain's excitatory neurotransmitter,
      and glucose, the energetic substrate of neural activity in reward-related neural
      processes. Here, we used high-speed amperometry with enzyme-based substrate
      sensitive and control, enzyme-free biosensors to examine second-scale
      fluctuations in the extracellular levels of these substances in the nucleus
      accumbens shell during glucose-drinking behavior in trained rats. Glutamate rose
      rapidly after the presentation of a glucose-containing cup and before the
      initiation of drinking (reward seeking), decreased more slowly to levels below
      baseline during consumption (sensory reward), and returned to baseline when the
      ingested glucose reached the brain (metabolic reward). When water was substituted
      for glucose, glutamate rapidly increased with cup presentation and in contrast to
      glucose drinking, increased above baseline after rats tasted the water and
      refused to drink further. Therefore, extracellular glutamate show distinct
      changes associated with key events of motivated drinking behavior and opposite
      dynamics during sensory and metabolic components of reward. In contrast to
      glutamate, glucose increased at each stimulus and behavioral event, showing a
      sustained elevation during the entire behavior and a robust post-ingestion rise
      that correlated with the gradual return of glutamate levels to their baseline. By
      comparing active drinking with passive intra-gastric glucose delivery, we
      revealed that fluctuations in extracellular glucose are highly dynamic,
      reflecting a balance between rapid delivery because of neural activity, intense
      metabolism, and the influence of ingested glucose reaching the brain.

PMID- 25393776
TI  - Silver nanoparticle toxicity to Atlantic killifish (Fundulus heteroclitus) and
      Caenorhabditis elegans: a comparison of mesocosm, microcosm, and conventional
      laboratory studies.
AB  - The use of silver nanoparticles (AgNPs) in consumer products and industrial
      applications, as well as their recent detection in waste streams, has created
      concern about potential impacts on aquatic ecosystems. The effect of complex
      environmental media on AgNP toxicity was investigated using wetland mesocosms and
      smaller scale microcosms. Mesocosms were dosed with 2.5 mg Ag/L as gum arabic
      (GA)-coated AgNPs, polyvinylpyrrolidone (PVP)-coated AgNPs, or AgNO3. Water
      samples were taken from mesocosms 24 h after dosing for acute toxicity tests with
      embryos and larvae of Atlantic killifish (Fundulus heteroclitus) and the nematode
      Caenorhabditis elegans. Acute toxicity tests were also performed on Atlantic
      killifish with AgNO3, GA AgNPs, and PVP AgNPs prepared in the laboratory with
      similar water. For killifish embryos, mesocosm samples were much less toxic than
      laboratory samples for all types of silver. For larvae, in contrast, all 3 silver
      mesocosm treatments exhibited toxicity. Interestingly, mesocosm samples of AgNO3
      were less toxic than laboratory samples; samples containing GA AgNPs were similar
      in toxicity, and samples containing PVP AgNPs were more toxic. For C. elegans,
      results were similar to killifish larvae. Results obtained from the mesocosms
      were not replicated on the smaller scale of the microcosms. These results
      indicate that environmental factors unique to the mesocosms acted differentially
      on AgNO3 to reduce its toxicity in a manner that does not translate to AgNPs for
      larval fish.

PMID- 25393777
TI  - Differential centrifugation-based biochemical fractionation of the Drosophila
      adult CNS.
AB  - Drosophila is widely used as a genetic model in questions of development,
      cellular function and disease. Genetic screens in flies have proven to be
      incredibly powerful in identifying crucial components for synapse formation and
      function, particularly in the case of the presynaptic release machinery. Although
      modern biochemical methods can identify individual proteins and lipids (and their
      binding partners), they have typically been excluded from use in Drosophila for
      technical reasons. To bridge this essential gap between genetics and
      biochemistry, we developed a fractionation method to isolate various parts of the
      synaptic machinery from Drosophila, thus allowing it to be studied in
      unprecedented biochemical detail. This is only possible because our protocol has
      unique advantages in terms of enriching and preserving endogenous protein
      complexes. The procedure involves decapitation of adult flies, homogenization and
      differential centrifugation of fly heads, which allow subsequent purification of
      presynaptic (and to a limited degree postsynaptic) components. It is designed to
      require only a rudimentary knowledge of biochemical fractionation, and it takes
      ~3.5 h. The yield is typically 4 mg of synaptic membrane protein per gram of
      Drosophila heads. 

PMID- 25393778
TI  - Using pancreas tissue slices for in situ studies of islet of Langerhans and
      acinar cell biology.
AB  - Studies on the cellular function of the pancreas are typically performed in vitro
      on its isolated functional units, the endocrine islets of Langerhans and the
      exocrine acini. However, these approaches are hampered by preparation-induced
      changes of cell physiology and the lack of an intact surrounding. We present here
      a detailed protocol for the preparation of pancreas tissue slices. This procedure
      is less damaging to the tissue and faster than alternative approaches, and it
      enables the in situ study of pancreatic endocrine and exocrine cell physiology in
      a conserved environment. Pancreas tissue slices facilitate the investigation of
      cellular mechanisms underlying the function, pathology and interaction of the
      endocrine and exocrine components of the pancreas. We provide examples for
      several experimental applications of pancreas tissue slices to study various
      aspects of pancreas cell biology. Furthermore, we describe the preparation of
      human and porcine pancreas tissue slices for the validation and translation of
      research findings obtained in the mouse model. Preparation of pancreas tissue
      slices according to the protocol described here takes less than 45 min from
      tissue preparation to receipt of the first slices. 

PMID- 25393779
TI  - CRISPR/Cas9-mediated conversion of eGFP- into Gal4-transgenic lines in zebrafish.
AB  - Here we present a protocol for the conversion of eGFP-transgenic zebrafish lines
      into lines expressing Gal4 from the same locus. This conversion allows the in
      depth analysis of the former eGFP-expressing cell population; with the Gal4
      upstream activating sequence (UAS) system, diverse UAS transgenes can be
      transactivated. Site-specific targeting of the gene encoding eGFP is achieved
      using the clustered regularly interspaced short palindromic repeats/CRISPR
      associated 9 (CRISPR/Cas9) system. A single-guide RNA (sgRNA) that targets eGFP
      is injected into embryos together with a donor vector containing an optimized
      version of Gal4 (KalTA4) to trigger integration of the donor into the targeted
      eGFP genomic location. To enable screening for successful integration events,
      injection is performed in a UAS:RFP transgenic background; fish showing mosaic
      eGFP-to-RFP conversion are raised to adulthood. The progeny of these adult fish
      are then screened for stable germline transmission, and converted progeny are
      used to generate stable lines. We have been able to generate two stably converted
      transgenic lines within 4 months. 

PMID- 25393780
TI  - The influence of feeding on the evolution of sensory signals: a comparative test
      of an evolutionary trade-off between masticatory and sensory functions of skulls
      in southern African horseshoe bats (Rhinolophidae).
AB  - The skulls of animals have to perform many functions. Optimization for one
      function may mean another function is less optimized, resulting in evolutionary
      trade-offs. Here, we investigate whether a trade-off exists between the
      masticatory and sensory functions of animal skulls using echolocating bats as
      model species. Several species of rhinolophid bats deviate from the allometric
      relationship between body size and echolocation frequency. Such deviation may be
      the result of selection for increased bite force, resulting in a decrease in
      snout length which could in turn lead to higher echolocation frequencies. If so,
      there should be a positive relationship between bite force and echolocation
      frequency. We investigated this relationship in several species of southern
      African rhinolophids using phylogenetically informed analyses of the allometry of
      their bite force and echolocation frequency and of the three-dimensional shape of
      their skulls. As predicted, echolocation frequency was positively correlated with
      bite force, suggesting that its evolution is influenced by a trade-off between
      the masticatory and sensory functions of the skull. In support of this, variation
      in skull shape was explained by both echolocation frequency (80%) and bite force
      (20%). Furthermore, it appears that selection has acted on the nasal capsules,
      which have a frequency-specific impedance matching function during vocalization.
      There was a negative correlation between echolocation frequency and capsule
      volume across species. Optimization of the masticatory function of the skull may
      have been achieved through changes in the shape of the mandible and associated
      musculature, elements not considered in this study.

PMID- 25393782
TI  - Fast human detection for intelligent monitoring using surveillance visible
      sensors.
AB  - Human detection using visible surveillance sensors is an important and
      challenging work for intruder detection and safety management. The biggest
      barrier of real-time human detection is the computational time required for dense
      image scaling and scanning windows extracted from an entire image. This paper
      proposes fast human detection by selecting optimal levels of image scale using
      each level's adaptive region-of-interest (ROI). To estimate the image-scaling
      level, we generate a Hough windows map (HWM) and select a few optimal image
      scales based on the strength of the HWM and the divide-and-conquer algorithm.
      Furthermore, adaptive ROIs are arranged per image scale to provide a different
      search area. We employ a cascade random forests classifier to separate candidate
      windows into human and nonhuman classes. The proposed algorithm has been
      successfully applied to real-world surveillance video sequences, and its
      detection accuracy and computational speed show a better performance than those
      of other related methods. 

PMID- 25393781
TI  - Acute cutaneous graft-vs.-host disease compared to drug hypersensitivity reaction
      with vacuolar interface changes: a blinded study of microscopic and
      immunohistochemical features.
AB  - BACKGROUND: Complications from graft-vs.-host disease (GVHD), a major contributor
      to morbidity and mortality following hematopoietic cell transplantation, may be
      mitigated by early diagnosis and intervention. However, differentiation between
      acute cutaneous GVHD and other common skin eruptions that develop in the post
      transplantation period, such as drug hypersensitivity reaction, can be
      challenging clinically and microscopically. Because recent evidence indicates
      that CD123, a marker of plasmacytoid dendritic cells, can help to distinguish
      gastrointestinal GVHD from the clinicopathologic mimic cytomegalovirus colitis,
      we aimed to determine whether CD123 could aid in the diagnosis of acute cutaneous
      GVHD. METHODS: We studied 12 skin specimens of patients with grades I-II
      cutaneous GVHD and 12 from patients who had drug hypersensitivity reaction with
      vacuolar interface changes on biopsy. RESULTS: No differences were seen between
      the two groups with regards to density or distribution of CD123 expression.
      Specimens representing GVHD showed significantly less spongiosis (P < 0.001) and
      fewer dermal eosinophils (P = 0.03) compared to those representing drug
      hypersensitivity reaction. CONCLUSIONS: We conclude that CD123 does not appear to
      be a useful ancillary test in the diagnosis of acute cutaneous GVHD. Careful
      correlation between clinical findings and features with microscopy remains the
      cornerstone of accurate diagnosis of acute cutaneous GVHD.

PMID- 25393783
TI  - The influence of random element displacement on DOA estimates obtained with
      (Khatri-Rao-)root-MUSIC.
AB  - Although a wide range of direction of arrival (DOA) estimation algorithms has
      been described for a diverse range of array configurations, no specific
      stochastic analysis framework has been established to assess the probability
      density function of the error on DOA estimates due to random errors in the array
      geometry. Therefore, we propose a stochastic collocation method that relies on a
      generalized polynomial chaos expansion to connect the statistical distribution of
      random position errors to the resulting distribution of the DOA estimates. We
      apply this technique to the conventional root-MUSIC and the Khatri-Rao-root-MUSIC
      methods. According to Monte-Carlo simulations, this novel approach yields a
      speedup by a factor of more than 100 in terms of CPU-time for a one-dimensional
      case and by a factor of 56 for a two-dimensional case. 

PMID- 25393784
TI  - Online variational Bayesian filtering-based mobile target tracking in wireless
      sensor networks.
AB  - The received signal strength (RSS)-based online tracking for a mobile node in
      wireless sensor networks (WSNs) is investigated in this paper. Firstly, a multi
      layer dynamic Bayesian network (MDBN) is introduced to characterize the target
      mobility with either directional or undirected movement. In particular, it is
      proposed to employ the Wishart distribution to approximate the time-varying RSS
      measurement precision's randomness due to the target movement. It is shown that
      the proposed MDBN offers a more general analysis model via incorporating the
      underlying statistical information of both the target movement and observations,
      which can be utilized to improve the online tracking capability by exploiting the
      Bayesian statistics. Secondly, based on the MDBN model, a mean-field variational
      Bayesian filtering (VBF) algorithm is developed to realize the online tracking of
      a mobile target in the presence of nonlinear observations and time-varying RSS
      precision, wherein the traditional Bayesian filtering scheme cannot be directly
      employed. Thirdly, a joint optimization between the real-time velocity and its
      prior expectation is proposed to enable online velocity tracking in the proposed
      online tacking scheme. Finally, the associated Bayesian Cramer-Rao Lower Bound
      (BCRLB) analysis and numerical simulations are conducted. Our analysis unveils
      that, by exploiting the potential state information via the general MDBN model,
      the proposed VBF algorithm provides a promising solution to the online tracking
      of a mobile node in WSNs. In addition, it is shown that the final tracking
      accuracy linearly scales with its expectation when the RSS measurement precision
      is time-varying. 

PMID- 25393785
TI  - The influence of nanopore dimensions on the electrochemical properties of
      nanopore arrays studied by impedance spectroscopy.
AB  - The understanding of the electrochemical properties of nanopores is the key
      factor for better understanding their performance and applications for nanopore
      based sensing devices. In this study, the influence of pore dimensions of
      nanoporous alumina (NPA) membranes prepared by an anodization process and their
      electrochemical properties as a sensing platform using impedance spectroscopy was
      explored. NPA with four different pore diameters (25 nm, 45 nm and 65 nm) and
      lengths (5 MUm to 20 MUm) was used and their electrochemical properties were
      explored using different concentration of electrolyte solution (NaCl) ranging
      from 1 to 100 MUM. Our results show that the impedance and resistance of
      nanopores are influenced by the concentration and ion species of electrolytes,
      while the capacitance is independent of them. It was found that nanopore
      diameters also have a significant influence on impedance due to changes in the
      thickness of the double layer inside the pores. 

PMID- 25393787
TI  - Using floating car data to analyse the effects of its measures and eco-driving.
AB  - The road transportation sector is responsible for around 25% of total man-made
      CO2 emissions worldwide. Considerable efforts are therefore underway to reduce
      these emissions using several approaches, including improved vehicle
      technologies, traffic management and changing driving behaviour. Detailed traffic
      and emissions models are used extensively to assess the potential effects of
      these measures. However, if the input and calibration data are not sufficiently
      detailed there is an inherent risk that the results may be inaccurate. This
      article presents the use of Floating Car Data to derive useful speed and
      acceleration values in the process of traffic model calibration as a means of
      ensuring more accurate results when simulating the effects of particular
      measures. The data acquired includes instantaneous GPS coordinates to track and
      select the itineraries, and speed and engine performance extracted directly from
      the on-board diagnostics system. Once the data is processed, the variations in
      several calibration parameters can be analyzed by comparing the base case model
      with the measure application scenarios. Depending on the measure, the results
      show changes of up to 6.4% in maximum speed values, and reductions of nearly 15%
      in acceleration and braking levels, especially when eco-driving is applied. 

PMID- 25393786
TI  - PERFORM: a system for monitoring, assessment and management of patients with
      Parkinson's disease.
AB  - In this paper, we describe the PERFORM system for the continuous remote
      monitoring and management of Parkinson's disease (PD) patients. The PERFORM
      system is an intelligent closed-loop system that seamlessly integrates a wide
      range of wearable sensors constantly monitoring several motor signals of the PD
      patients. Data acquired are pre-processed by advanced knowledge processing
      methods, integrated by fusion algorithms to allow health professionals to
      remotely monitor the overall status of the patients, adjust medication schedules
      and personalize treatment. The information collected by the sensors
      (accelerometers and gyroscopes) is processed by several classifiers. As a result,
      it is possible to evaluate and quantify the PD motor symptoms related to end of
      dose deterioration (tremor, bradykinesia, freezing of gait (FoG)) as well as
      those related to over-dose concentration (Levodopa-induced dyskinesia (LID)).
      Based on this information, together with information derived from tests performed
      with a virtual reality glove and information about the medication and food
      intake, a patient specific profile can be built. In addition, the patient
      specific profile with his evaluation during the last week and last month, is
      compared to understand whether his status is stable, improving or worsening.
      Based on that, the system analyses whether a medication change is needed--always
      under medical supervision--and in this case, information about the medication
      change proposal is sent to the patient. The performance of the system has been
      evaluated in real life conditions, the accuracy and acceptability of the system
      by the PD patients and healthcare professionals has been tested, and a comparison
      with the standard routine clinical evaluation done by the PD patients' physician
      has been carried out. The PERFORM system is used by the PD patients and in a
      simple and safe non-invasive way for long-term record of their motor status, thus
      offering to the clinician a precise, long-term and objective view of patient's
      motor status and drug/food intake. Thus, with the PERFORM system the clinician
      can remotely receive precise information for the PD patient's status on previous
      days and define the optimal therapeutical treatment.

PMID- 25393788
TI  - Prospective study of sickle cell trait and venous thromboembolism incidence.
AB  - BACKGROUND: Sickle cell trait may increase risk of venous thromboembolism, but
      this is not fully established. OBJECTIVES: We sought to determine the association
      of sickle cell trait with deep vein thrombosis and pulmonary embolism. METHODS:
      Middle-aged African Americans participating in a prospective, population-based
      cohort investigation, the Atherosclerosis Risk in Communities Study, were
      followed from 1987 through 2011 for incident hospitalized pulmonary embolism (n =
      111) or isolated deep vein thrombosis (n = 138), verified by physician review of
      medical records. Sickle cell trait (heterozygosity for hemoglobin S, n = 268) was
      compared with no sickle cell trait (n = 3748). RESULTS: Over a median of 22 years
      of follow-up, 249 participants had an incident venous thromboembolism. The hazard
      ratio of venous thromboembolism was 1.50 (95% confidence interval [CI] 0.96-2.36)
      for participants with vs. without sickle cell trait, after adjustment for age,
      sex, ancestry, hormone replacement therapy (women), body mass index, diabetes,
      and estimated glomerular filtration rate. This hazard ratio was 2.05 (95% CI 1.12
      3.76) for pulmonary embolism and 1.15 (95% CI 0.58-2.27) for deep vein thrombosis
      without pulmonary embolism. CONCLUSIONS: Sickle cell trait in African Americans
      carries a 2-fold increased risk of pulmonary embolism but does not elevate deep
      vein thrombosis risk. Because neonatal screening for sickle hemoglobin is being
      conducted in the United States, consideration should be paid to the increased
      pulmonary embolism risk of individuals with sickle cell trait.

PMID- 25393790
TI  - Thymic tumors: adopting an orphan thoracic tumor as a model of personalized
      medicine.

PMID- 25393791
TI  - Forty years of the international association for study of lung cancer pathology
      committee.
AB  - Lung cancer classification during the last four decades has undergone major
      changes and evolution, mostly lead by pathologists who were actively involved in
      the International Association for the Study of Lung Cancer (IASLC) Pathology
      Committee. The Committee members have led the development and writing of the
      second (1981), third (1999 and 2004), and fourth (2015) editions of the World
      Health Organization classifications on lung tumors. Committee members were
      responsible for defining and refining the classifications of small-cell carcinoma
      and adenocarcinoma subtypes that are relevant to their clinical behavior.
      Particularly notable was development of the 2011 IASLC/American Thoracic
      Society/European Respiratory Society international, multidisciplinary lung
      adenocarcinoma classification. The multidisciplinary approach that represents the
      IASLC culture in research, education, and practice in clinical management of lung
      cancer patients have paved the way for integrating pathology practice into the
      new era of personalized cancer care. 

PMID- 25393792
TI  - Long-term results after treatment for recurrent thymoma: a multicenter analysis.
AB  - OBJECTIVES: The treatment for recurrent thymoma remains a very controversial
      issue. This study aims to investigate the long-term outcomes in patients with
      relapse according to treatment strategies and clinicopathological features.
      METHODS: We retrospectively analyzed the database of three tertiary centers of
      thoracic surgery with the aim of reviewing the clinical records of 81 patients
      who experienced a recurrent thymoma after radical thymectomy, in the period
      between January 2001 and June 2013. The staging of both primitive and recurrent
      thymomas were based on the surgical and pathological criteria described by
      Masaoka. Experienced pathologists reassessed independently the histology of the
      initial thymoma and its relapse, according to the WHO classification. To the
      purposes of this study R+ resection or thymic carcinoma were considered as
      exclusion criteria. The overall outcome for long-term (5 years and 10 years)
      survival and disease-free survival after initial thymectomy and after treatment
      of recurrent thymoma were analyzed using standard statistics. RESULTS: The
      population was gender balanced (41 M, 40 F), mean age: 46.4 +/- 12.3 years. Fifty
      four patients (66.7%) were affected by myasthenia gravis, while the other 14 by
      other paraneoplastic conditions. Surgery was performed in 61 patients (75.3%,),
      and radiotherapy and/or chemotherapy in 14 patients (17.3%). The mean follow-up
      duration after recurrence onset was 66.3 +/- 56.4 months. Adjuvant therapy had no
      effect on prolonging the disease-free survival: no differences were found when
      investigating the administration of adjuvant chemotherapy (no CHT = 91.5 +/- 76.4
      months versus yes CHT=64.0 +/- 41.3) and radiotherapy (no RT=86.2 +/- 72.8 months
      versus yes RT= 93.0 +/- 62.3; p = 0.8). Relapses were mostly local (mediastinum:
      15 cases, pleura: 44 cases); hematogenous distant recurrences were observed in 15
      cases (lung: 12; liver: 1; bone: 2 cases). An upgrade in the WHO class (defined
      as the "migration" of WHO class at initial thymectomy to more aggressive WHO
      class assigned at thymic recurrence resection) was found in 25/61 cases (40.9%),
      but this phenomenon apparently did not influence patient's prognosis. Overall,
      the 5- and 10-year survival rates after the initial thymectomy were 94.8% and
      71.7%, respectively, while the 5- and 10-year survival rates after the treatment
      of the recurrence at the thymic level were 73.6% and 48.3%, respectively (82.4%
      at 5 years and 65.4% at 10 years when a R0-re-resection was obtained). The
      analysis on the trends of disease-free survival indicated that the site of
      recurrence (hematogenous diffusion) seems to be associated to a higher risk of re
      relapse (p = 0.01). CONCLUSIONS: Even following a thymectomy performed with
      radical intent, thymoma may recur several years later, usually as a locoregional
      relapse. A rewarding long-term survival may be expected after treatment,
      especially when a re-resection (radical) is performed (82.4% at 5 years). An
      histopathological "WHO upgrade" (from "low-risk" WHO classes at thymectomy to
      "high-risk classes" at relapse) may be observed in a remarkable percentage of
      patients (nearly 40% in this series), but this phenomenon seems to be not
      correlated with any worsening of the prognosis.

PMID- 25393793
TI  - Phase II study of Amrubicin combined with carboplatin for thymic carcinoma and
      invasive thymoma: North Japan Lung Cancer group study 0803.
AB  - BACKGROUND: There has been no standard chemotherapy for advanced or recurrent
      thymic malignancies including thymic carcinoma (TC) and invasive thymoma (IT),
      though platinum and anthracycline have been reported as effective agents for the
      treatment of these diseases. The objective of this study was to evaluate the
      efficacy and safety of the combination of amrubicin (AMR), a new anthracycline
      agent, and carboplatin (CBDCA) in patients with advanced thymic malignancies.
      METHODS: Patients with histologically confirmed thymic malignancies received AMR
      (35 mg/m, days 1-3) and CBDCA (area under the curve 4.0, day 1) every 3 weeks.
      Patients who had received previous chemotherapy were treated with a reduced dose
      of AMR (30 mg/m). The primary end point was objective response rate (ORR), and
      secondary endpoints were progression-free survival, overall survival, and
      toxicity profile. RESULTS: From December 2008 to October 2012, 51 patients (33 TC
      and 18 IT) were enrolled. The median number of treatment cycles was four in each
      group. The ORR and progression-free survival were 30% (95% confidence interval,
      14-46) and 7.6 months in the TC group, and 17% (95% confidence interval, 0-34)
      and 7.6 months in the IT group, respectively. The ORR of TC patients without
      previous chemotherapy (n = 19) was 42%. Although grade 3 or 4 hematological
      toxicities were common including neutropenia (82%) and febrile neutropenia (22%),
      these were transient and manageable. Nonhematological toxicities were moderate
      and no treatment-related death was observed. CONCLUSIONS: The combination of AMR
      with CBDCA was active for TC with acceptable toxicity, although it was not
      effective for IT. Further investigation of this regimen for advanced TC is
      warranted.

PMID- 25393794
TI  - Clinical characteristics and outcomes for patients with thymic carcinoma:
      evaluation of Masaoka staging.
AB  - BACKGROUND: Thymic carcinomas are rare cancers with limited data regarding
      outcomes, particularly for those patients with advanced disease. METHODS: We
      identified patients with thymic carcinomas diagnosed between 1993 and 2012.
      Patient characteristics, recurrence-free survival (RFS), and overall survival
      (OS) were analyzed. RESULTS: One hundred twenty-one patients with thymic
      carcinomas were identified. Higher Masaoka stage was associated with worse OS and
      RFS (5-year OS of 100%, 81%, 51%, 24%, and 17% for stage I, II, III, IVa, and IVb
      respectively, p < 0.001 and 5-year RFS of 80%, 28%, and 7% for stage I/II, III,
      and IV respectively, p < 0.001). Patients with stage IVb lymph node (LN) only
      disease had a better 5-year OS as compared with patients with distant metastasis
      (24% versus 7%, p = 0.025). Of the 61 patients with stage IVb disease, 22 of 29
      patients (76%) with LN-only disease underwent curative intent resection versus 3
      of 32 patients (9%) with distant metastasis. Twenty-two patients with LN
      involvement were treated with multimodality therapy. Three (14%) remain free of
      disease with long-term follow-up (range, 3.4+ years- to 6.8+ years). CONCLUSIONS:
      We describe the clinical features of a large series of patients with thymic
      carcinoma in North America. The Masaoka staging system effectively prognosticated
      OS and RFS. Patients with stage IVb LN-only disease had significantly better OS
      as compared with patients with distant metastasis with a subset of patients
      sustaining long-term RFS with multimodality therapy. If validated, these data
      would support a revised staging system with subclassification of stage IVb
      disease into two groups.

PMID- 25393795
TI  - Assessment of ALK status by FISH on 1000 Spanish non-small cell lung cancer
      patients.
AB  - INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) harboring
      anaplastic lymphoma kinase (ALK) rearrangement selectively respond to ALK
      inhibitors. Thus, identification of ALK rearrangements has become a standard
      diagnostic test in advanced NSCLC patients. Our institution has been a referral
      center in Spain for ALK determination by Fluorescent in situ hybridization
      (FISH). The aim of our study was to assess the feasibility and the FISH patterns
      of the ALK gene and to evaluate the clinical and pathological features of
      patients with ALK alterations. METHODS: Between 2010 and 2014, 1092 samples were
      evaluated for ALK using FISH technique (927 histological samples, 165 cytological
      samples). Correlation with available clinical-pathological information was
      assessed. RESULTS: ALK rearrangement was found in 35 patients (3.2%). Cytological
      samples (using either direct smears or cell blocks), were more frequently non
      assessable than histological samples (69% versus 89%, respectively) (p < 0.001).
      Within the ALK-rearranged cases the majority were female, non-smokers, and stage
      IV. CONCLUSIONS: Although assessable in cytological samples, biopsies are
      preferred when available for ALK evaluation by FISH. The ALK translocation
      prevalence and the associated clinico-pathological features in Spanish NSCLC
      patients are similar to those previously reported.

PMID- 25393796
TI  - Identification of a novel HIP1-ALK fusion variant in Non-Small-Cell Lung Cancer
      (NSCLC) and discovery of ALK I1171 (I1171N/S) mutations in two ALK-rearranged
      NSCLC patients with resistance to Alectinib.
AB  - Huntingtin-interacting protein 1 (HIP1) has recently been identified as a new
      fusion partner fused to anaplastic lymphoma kinase (ALK) in non-small-cell lung
      cancer (NSCLC). To date, two variants of HIP1-ALK (H21; A20) and (H28; A20) have
      been identified in NSCLC. However, the response of patients with NSCLC harboring
      HIP1-ALK to ALK inhibitors and potential resistance mechanisms to such remain
      unknown. Here, we report a patient with NSCLC harboring a novel HIP1-ALK fusion
      variant (H30; A20). This patient and another patient with EML4-ALK variant 3a/b
      initially responded sequentially to crizotinib and then alectinib, a next
      generation ALK inhibitor, but developed acquired resistance to alectinib with the
      presence of a mutation in amino acid residue 1171 (I1171N and I1171S
      respectively) located in the hydrophobic regulatory spine (R-spine) of the ALK
      kinase in both the cases as identified by a comprehensive next-generation
      sequencing-based assay performed on biopsies of new liver metastases that
      developed during alectinib treatment. 

PMID- 25393797
TI  - Resection of a solitary pulmonary metastasis from prostatic Adenocarcinoma
      misdiagnosed as a Bronchocele: usefulness of 18F-choline and 18F-FDG PET/CT.

PMID- 25393798
TI  - Secondary mutations at I1171 in the ALK gene confer resistance to both Crizotinib
      and Alectinib.

PMID- 25393799
TI  - The European Young Chemist Award 2014.
AB  - The future's bright! The European Young Chemist Award for 2014 was awarded at the
      5th EuCheMS Chemistry Congress in Instanbul. Impressions and reflections from the
      Convener of the event, Professor Bruno Pignataro, are given in the Guest
      Editorial. 

PMID- 25393800
TI  - Effectiveness of maxillary protraction using a hybrid hyrax-facemask combination:
      a controlled clinical study.
AB  - OBJECTIVE: To evaluate the treatment effects of a hybrid hyrax-facemask (FM)
      combination in growing Class III patients. MATERIAL AND METHODS: A sample of 16
      prepubertal patients (mean age, 9.5 +/- 1.6 years) was investigated by means of
      pre- and posttreatment cephalograms. The treatment comprised rapid palatal
      expansion with a hybrid hyrax, a bone- and toothborne device. Simultaneously,
      maxillary protraction using an FM was performed. Mean treatment duration was 5.8
      +/- 1.6 months. The treatment group was compared with a matched control group of
      16 untreated Class III subjects. Statistical comparisons were performed with the
      Mann-Whitney U-test. RESULTS: Significant improvement in skeletal sagittal values
      could be observed in the treatment group over controls: SNA: 2.4 degrees , SNB: 
      1.7 degrees , Co-Gn: -2.3 mm, Wits appraisal: 4.5 mm. Regarding vertical changes,
      maintenance of vertical growth was obtained as shown by a small nonsignificant
      increase of FMA and a small significant decrease of the Co-Go-Me angle.
      CONCLUSIONS: The hybrid hyrax-FM combination was found to be effective for
      orthopedic treatment in growing Class III patients in the short term. Favorable
      skeletal changes were observed both in the maxilla and in the mandible. No
      dentoalveolar compensations were found.

PMID- 25393801
TI  - Contribution of cone beam computed tomography to the detection of apical root
      resorption after orthodontic treatment in root-filled and vital teeth.
AB  - OBJECTIVE: To investigate whether root-filled teeth are similar to vital pulp
      teeth in terms of apical root resorption (ARR) after orthodontic treatment.
      MATERIALS AND METHODS: An original sample of cone beam computed tomography (CBCT)
      images of 1256 roots from 30 orthodontic patients were analyzed. The inclusion
      criteria demanded root-filled teeth and their contralateral vital teeth, while
      teeth with history of trauma had to be excluded to comply with exclusion
      criteria. CBCT images of root-filled teeth were compared before and after
      orthodontic treatment in a split-mouth design study. Tooth measurements were made
      with multiplanar reconstruction using axial-guided navigation. The statistical
      difference between the treatment effects was compared using the paired t-test.
      RESULTS: Twenty posterior root-filled teeth and their contralaterals with vital
      pulp were selected before orthodontic treatment from six adolescents (two boys
      and four girls; mean [SD] age 12.8 [1.8] years). No differences were detected
      between filled and vital root lengths before treatment (P  =  .4364). The mean
      differences in root length between preorthodontic and postorthodontic treatment
      in filled- and vital roots were -0.30 mm and -0.16 mm, respectively, without any
      statistical difference (P  =  .4197) between them. CONCLUSION: There appears to
      be no increase in ARR after orthodontic treatment in root-filled teeth with no
      earlier ARR.

PMID- 25393802
TI  - Interproximal reduction of teeth: differences in perspective between
      orthodontists and dentists.
AB  - OBJECTIVE: To determine if interproximal reduction of teeth (IPR) is perceived
      differently by orthodontists and general dentists. MATERIALS AND METHODS: A Web
      based survey containing statements about IPR was developed and randomly
      distributed to orthodontists and general dentists. RESULTS: The majority of
      orthodontists and general dentists strongly agreed that IPR is a minimally
      invasive procedure that poses little risk for the development of interproximal
      decay. However, general dentists were more likely to perform post-IPR polishing
      and to apply topical fluoride than are orthodontists (P < .0001). A greater
      percentage of orthodontists strongly believed that the esthetic and occlusal
      benefits of IPR outweigh the potential risk of tooth decay when IPR was performed
      (P < .0001). A greater percentage of general dentists were hesitant to perform
      IPR, despite research supporting that IPR has little negative effect on the
      health of teeth. CONCLUSIONS: The results of this study disproved the null
      hypothesis that orthodontists and general dentists share similar views regarding
      the use of IPR during orthodontic treatment. General dentists were more
      conservative in their views of IPR and were less comfortable with performing IPR
      as a routine procedure. General dentists felt more strongly about the importance
      of post-IPR polishing and application of topical fluoride. Orthodontists were
      more likely to have researched the long-term effects of IPR on the health of
      teeth and therefore felt more comfortable performing IPR during orthodontic
      treatment.

PMID- 25393803
TI  - Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10-60
      containing fusion protein in the marmoset experimental autoimmune
      encephalomyelitis model.
AB  - Current therapies for multiple sclerosis (MS), a chronic autoimmune
      neuroinflammatory disease, mostly target general cell populations or immune
      molecules, which may lead to a compromised immune system. A more directed
      strategy would be to re-enforce tolerance of the autoaggressive T cells that
      drive tissue inflammation and injury. In this study, we have investigated whether
      the course of experimental autoimmune encephalomyelitis (EAE) in mice and
      marmosets can be altered by a potent tolerizing fusion protein. In addition, a
      multi-parameter immunological analysis was performed in marmosets to assess
      whether the treatment induces modulation of EAE-associated cellular and humoral
      immune reactions. The fusion protein, CTA1R9K-hMOG10-60-DD, contains a mutated
      cholera toxin A1 subunit (CTA1R9K), a dimer of the Ig binding D region of
      Staphylococcus aureus protein A (DD), and the human myelin oligodendrocyte
      glycoprotein (hMOG) sequence 10-60. We observed that intranasal application of
      CTA1R9K-hMOG10-60-DD seems to skew the immune response against myelin
      oligodendrocyte glycoprotein (MOG) towards a regulatory function. We show a
      reduced number of circulating macrophages, reduced MOG-induced expansion of
      mononuclear cells in peripheral blood, reduced MOG-induced production of
      interleukin (IL)-17A in spleen, increased MOG-induced production of IL-4 and IL
      10 and an increased percentage of cells expressing programmed cell death-1 (PD-1)
      and CC chemokine receptor 4 (CCR4). Nevertheless, the treatment did not
      detectably change the EAE course and pathology. Thus, despite a detectable effect
      on relevant immune parameters, the fusion protein failed to influence the
      clinical and pathological outcome of disease. This result warrants further
      development and improvement of this specifically targeted tolerance inducing
      therapy. 

PMID- 25393804
TI  - Regulatory T-cell and T-helper 17 balance in chronic lymphocytic leukemia
      progression and autoimmune cytopenias.
AB  - The reasons for progression and autoimmune cytopenias (AIC) in chronic
      lymphocytic leukemia (CLL) are not entirely clear, with previous studies
      suggesting a role for regulatory T-cells (Treg). In this study we prospectively
      studied Treg (CD3+CD4+CD25highCD127low), interleukin-10 (IL-10) producing Treg
      and T-helper 17 (Th17) (CD3+CD4+IL-17+) cells in 40 treatment-naive patients with
      CLL. The percentage of Th17 and not Treg cells was significantly higher in the
      AIC cohort than in those without AIC (p<0.0001). The Treg:Th17 ratio was skewed
      in favor of Th17 in the AIC cohort (p=0.02). Th17 cells are responsible for AIC
      of CLL. Analysis of lymph-node aspirates showed that the percentage of Treg and
      IL-10 expression in Treg and not Th17 was significantly higher than in peripheral
      blood (p<0.01). Treg cells play a major role in the microenvironment where
      disease progression occurs. This shows the importance of maintaining the
      Treg:Th17 equilibrium, for imbalance leads to CLL progression or AIC.

PMID- 25393805
TI  - Changes in the use of radiation therapy for early classical Hodgkin lymphoma in
      adolescents and young adults: implications for survival and second malignancies.
AB  - Omission of radiation therapy (RT) in adolescents and young adults (AYA) with
      early classical Hodgkin lymphoma (cHL) may affect survival and risk of second
      malignancies (SMN). Using the Surveillance, Epidemiology and End Results database
      we found reduction in RT use from 60.8% among 2614 cases from 1995 to 2002 to
      52.9% among 2542 cases from 2003 to 2010, p<0.001. Survival at 5 years with and
      without RT was 95.1% vs. 93.3%, p=0.013 for 1995-2002 and 97.7% vs. 96.4%,
      p=0.021 for 2003-2010. Omission of RT was affected by 2003-2010 era, race
      ethnicity, income and education and independently increased the risk of death
      (hazard ratio 1.34, p=0.011). The cumulative risk of SMN at 150 months was 3.3%
      vs. 3.0% (p=0.87) while the risk of death without SMN (competing risk) was 5.7%
      vs. 8.8% for RT and no-RT patients, respectively (p=0.0009). Omission of RT for
      early cHL in AYA may increase mortality without reduction in SMN.

PMID- 25393806
TI  - Cost-effectiveness of the sequential application of tyrosine kinase inhibitors
      for the treatment of chronic myeloid leukemia.
AB  - Several tyrosine kinase inhibitors (TKIs) are approved for chronic myeloid
      leukemia (CML) therapy. We evaluated the long-term cost-effectiveness of seven
      sequential therapy regimens for CML in Austria. A cost-effectiveness analysis was
      performed using a state-transition Markov model. As model parameters, we used
      published trial data, clinical, epidemiological and economic data from the
      Austrian CML registry and national databases. We performed a cohort simulation
      over a life-long time-horizon from a societal perspective. Nilotinib without
      second-line TKI yielded an incremental cost-utility ratio of 121,400 ?/quality
      adjusted life year (QALY) compared to imatinib without second-line TKI after
      imatinib failure. Imatinib followed by nilotinib after failure resulted in
      131,100 ?/QALY compared to nilotinib without second-line TKI. Nilotinib followed
      by dasatinib yielded 152,400 ?/QALY compared to imatinib followed by nilotinib
      after failure. Remaining strategies were dominated. The sequential application of
      TKIs is standard-of-care, and thus, our analysis points toward imatinib followed
      by nilotinib as the most cost-effective strategy.

PMID- 25393807
TI  - A nasal mass discovered during intubation. Schwannoma.

PMID- 25393809
TI  - Development of the Universal Form Of Treatment Options (UFTO) as an alternative
      to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders: a cross
      disciplinary approach.
AB  - RATIONALE AIMS AND OBJECTIVES: Problems exist with Do Not Attempt Cardiopulmonary
      Resuscitation (DNACPR) orders: they are often misinterpreted by clinicians to
      mean that other treatments should be withheld; resuscitation decision discussions
      are difficult; patients remain inappropriately for resuscitation. We developed an
      alternative approach. METHODS: An adapted Delphi method was used. Senior
      clinicians were interviewed about the strengths and weakness of current practice.
      Teams who had initiated alternative approaches internationally were contacted.
      Focus groups were conducted with doctors, nurses and patients to further
      understand problems with DNACPR orders and establish essential aspects of a new
      approach. A behavioral economist and management consultant contributed advice.
      The resulting form was recirculated and further refined. It was: snowballed out
      to others with specialist expertise (palliative care physicians, intensivists,
      etc) for further feedback; assessed in simulated clinical encounters before being
      piloted; further adjusted once in clinical practice. In parallel, a patient
      information leaflet was developed along with education materials. RESULTS:
      Consensus was achieved that the new approach should: be universal; have
      discussions and clinical conditions documented first; clarify goals of overall
      treatment (active treatment or optimal supportive care); contextualize the
      resuscitation decision among other treatment decisions; have a free text box for
      'opting out' of invasive treatments, rather than tick boxes; be green; be limited
      to one page. CONCLUSIONS: The Universal Form of Treatment Options was developed
      iteratively with patients, doctors and nurses as an alternative approach to
      resuscitation decisions. This paper illustrates a cross-disciplinary approach to
      developing practical alternatives in health care.

PMID- 25393810
TI  - Detection of contaminating enzymatic activity in plant-derived recombinant
      biotechnology products.
AB  - Residual impurities in recombinantly produced protein biologics, such as host
      cell proteins (HCP), can potentially cause unwanted toxic or immunogenic
      responses in patients. Additionally, undetected impurities found in recombinant
      proteins used in cell culture may adversely impact basic research and
      biotechnology applications. Currently, the enzyme-linked immunosorbent assay
      (ELISA) is the standard for detection of residual HCP contamination in
      recombinantly produced biologics. Alternatively, two-dimensional liquid
      chromatography coupled to mass spectrometry is being developed as a tool for
      assessing this critical quality attribute. Both of these methods rely on the
      direct detection of HCPs and some previous knowledge of the contaminant. For
      contaminating enzymes, the mass level of the impurity may fall below the
      threshold of detection of these methods and underestimate the true impact. To
      address this point, here we demonstrate facile detection and characterization of
      contaminating phytase activity in rice-derived recombinant human serum albumin
      (rHSA) using a sensitive, label-free nuclear magnetic resonance (NMR)
      spectroscopy assay. We observed varying degrees of phytase contamination in
      biotechnology-grade rHSA from various manufacturers by monitoring the degradation
      of adenosine-5'-triphosphate and myo-inositol-1,2,3,4,5,6-hexakisphosphate by
      (31)P NMR. The observed lot-to-lot variability may result in irreproducible cell
      culture results and should be evaluated as a possible critical quality attribute
      in plant-derived biotherapeutics. 

PMID- 25393808
TI  - The relationship between obsessive-compulsive symptoms and PARKIN genotype: The
      CORE-PD study.
AB  - BACKGROUND: Few studies have systematically investigated the association between
      PARKIN genotype and psychiatric co-morbidities of Parkison's disease (PD). PARKIN
      associated PD is characterized by severe nigral dopaminergic neuronal loss, a
      finding that may have implications for behaviors rooted in dopaminergic circuits
      such as obsessive-compulsive symptoms (OCS). METHODS: The Schedule of Compulsions
      and Obsessions Patient Inventory (SCOPI) was administered to 104 patients with
      early-onset PD and 257 asymptomatic first-degree relatives. Carriers of one and
      two PARKIN mutations were compared with noncarriers. RESULTS: Among patients,
      carriers scored lower than noncarriers in adjusted models (one-mutation: 13.9
      point difference, P = 0.03; two-mutation: 24.1, P = 0.001), where lower scores
      indicate less OCS. Among asymptomatic relatives, a trend toward the opposite was
      seen: mutation carriers scored higher than noncarriers (one mutation, P = 0.05;
      two mutations, P = 0.13). CONCLUSIONS: First, a significant association was found
      between PARKIN mutation status and obsessive-compulsive symptom level in both PD
      and asymptomatic patients, suggesting that OCS might represent an early non-motor
      dopamine-dependent feature. Second, irrespective of disease status, heterozygotes
      were significantly different from noncarriers, suggesting that PARKIN
      heterozygosity may contribute to phenotype. (c) 2014 International Parkinson and
      Movement Disorder Society.

PMID- 25393811
TI  - Evaluation of a digital learning object (DLO) to support the learning process in
      radiographic dental diagnosis.
AB  - AIMS: Studies have shown that inappropriate therapeutic strategies may be adopted
      if crown and root changes are misdiagnosed, potentially leading to undesirable
      consequences. Therefore, the aim of this study was to evaluate a digital learning
      object, developed to improve skills in diagnosing radiographic dental changes.
      MATERIALS AND METHODS: The object was developed using the Visual Basic
      Application (VBA) software and evaluated by 62 undergraduate students (male: 24
      and female: 38) taking an imaging diagnosis course. Participants were divided in
      two groups: test group, which used the object and control group, which attended
      conventional classes. After 3 weeks, students answered a 10-question test and
      took a practice test to diagnose 20 changes in periapical radiographs. RESULTS:
      The results show that test group performed better that control group in both
      tests, with statistically significant difference (P = 0.004 and 0.003,
      respectively). In overall, female students were better than male students.
      Specific aspects of object usability were assessed using a structured
      questionnaire based on the System Usability Scale (SUS), with a score of 90.5 and
      81.6 by male and female students, respectively. CONCLUSIONS: The results obtained
      in this study suggest that students who used the DLO performed better than those
      who used conventional methods. This suggests that the DLO may be a useful
      teaching tool for dentistry undergraduates, on distance learning courses and as a
      complementary tool in face-to-face teaching.

PMID- 25393813
TI  - Adult Physical Activity Counseling by Health Professionals in Brazil: A National
      Urban Population Survey.
AB  - BACKGROUND: Physical activity counseling is an attribution of health
      professionals. As such, this paper aims to analyze the receipt of this form of
      counseling. METHODS: Cross-sectional national study interviewing 12,402 adults
      living in the urban area of 100 Brazilian municipalities. RESULTS: Overall
      counseling prevalence was 30%, falling to 20% when considering only counseling
      provided by health professionals. Counseling was significantly more frequent
      among women and among individuals who were older, married, had higher
      socioeconomic status, were former smokers, physically active, and reporting
      hypertension, diabetes, and excess weight. CONCLUSIONS: Little counseling was
      found to be done, this being a missed opportunity for health promotion. Health
      services and professionals therefore need to be trained and encouraged to provide
      adequate information to all health service users on the benefits of leading
      healthy lifestyles.

PMID- 25393812
TI  - The scars of childhood adversity: minor stress sensitivity and depressive
      symptoms in remitted recurrently depressed adult patients.
AB  - BACKGROUND: Childhood adversity may lead to depressive relapse through its long
      lasting influence on stress sensitivity. In line with the stress sensitization
      hypothesis, minor (daily) stress is associated with depressive relapse.
      Therefore, we examine the impact of childhood adversity on daily stress and its
      predictive value on prospectively assessed depressive symptoms in recurrently
      depressed patients. METHOD: Daily stress was assessed in recurrently depressed
      adult patients, enrolled into two randomized trials while remitted. The reported
      intensity and frequency of dependent and independent daily stress was assessed at
      baseline. Independent stress is externally generated, for example an accident
      happening to a friend, while dependent stress is internally generated, for
      example getting into a fight with a neighbor. Hierarchical regression analyses
      were performed with childhood adversity, independent and dependent daily stress
      as predictor variables of prospectively measured depressive symptoms after three
      months of follow-up (n = 138). RESULTS: We found that childhood adversity was not
      significantly associated with a higher frequency and intensity of daily stress.
      The intensity of both independent and dependent daily stress was predictive of
      depressive symptom levels at follow-up (unadjusted models respectively: B = 0.47,
      t = 2.05, p = 0.041, 95% CI = 0.02-0.92; B = 0.29, t = 2.20, p = 0.028, 95% CI =
      0.03-0.55). No associations were found between childhood adversity and depressive
      symptoms at follow-up. CONCLUSION: No evidence was found supporting stress
      sensitization due to the experience of childhood adversity in this recurrently
      depressed but remitted patient group. Nevertheless, our research indicates that
      daily stress might be a target for preventive treatment. TRIAL REGISTRATION:
      Trial A: Nederlands Trial Register NTR1907 Trial B: Nederlands Trial Register
      NTR2503.

PMID- 25393814
TI  - Urbanization increases Aedes albopictus larval habitats and accelerates mosquito
      development and survivorship.
AB  - INTRODUCTION: Aedes albopictus is a very invasive and aggressive insect vector
      that causes outbreaks of dengue fever, chikungunya disease, and yellow fever in
      many countries. Vector ecology and disease epidemiology are strongly affected by
      environmental changes. Urbanization is a worldwide trend and is one of the most
      ecologically modifying phenomena. The purpose of this study is to determine how
      environmental changes due to urbanization affect the ecology of Aedes albopictus.
      METHODS: Aquatic habitats and Aedes albopictus larval population surveys were
      conducted from May to November 2013 in three areas representing rural, suburban,
      and urban settings in Guangzhou, China. Ae. albopictus adults were collected
      monthly using BG-Sentinel traps. Ae. albopictus larva and adult life-table
      experiments were conducted with 20 replicates in each of the three study areas.
      RESULTS: The urban area had the highest and the rural area had the lowest number
      of aquatic habitats that tested positive for Ae. albopictus larvae. Densities in
      the larval stages varied among the areas, but the urban area had almost two-fold
      higher densities in pupae and three-fold higher in adult populations compared
      with the suburban and rural areas. Larvae developed faster and the adult
      emergence rate was higher in the urban area than in suburban and rural areas. The
      survival time of adult mosquitoes was also longer in the urban area than it was
      in suburban and rural areas. Study regions, surface area, water depth, water
      clearance, surface type, and canopy coverage were important factors associated
      with the presence of Ae. albopictus larvae. CONCLUSIONS: Urbanization
      substantially increased the density, larval development rate, and adult survival
      time of Ae. albopictus, which in turn potentially increased the vector capacity,
      and therefore, disease transmissibility. Mosquito ecology and its correlation
      with dengue virus transmission should be compared in different environmental
      settings.

PMID- 25393821
TI  - Hematopoietic stem cell transplantation in infants.
AB  - BACKGROUND: It is rare for infants, who are less than 365 days old, to receive
      hematopoietic stem cell transplantation (HSCT). Our objective was to review the
      indications, survival, and late effects of infants who received HSCT. PROCEDURE:
      Between April 1992 and March 2010, a total of 1,363 children underwent HSCT (775
      allogeneic [allo]; 588 autologous [auto]) in the Hospital for Sick Children,
      Toronto. Of these, 51 (3.7%) were infants. RESULTS: Seventeen infants received
      allo HSCT for a genetic metabolic disorder. The median age at HSCT was 211 days
      (29-334 days). After median follow-up of 8.9 years (2.9-20.2 years), 12 patients
      remained alive, representing an overall survival rate of 70%. Infants with non
      metabolic disorders (n = 34); 10 (three neuroblastoma [NBL], three brain tumor,
      two acute meylogenous leukemia [AML], one rhabdomyosarcoma, and one
      retinoblastoma) received auto HSCT, and 24 (eight hemophagocytic
      lymphohistiocytosis [HLH], four juvenile meylomonocytic leukemia [JMML], four
      Wiscott-Aldrych Syndrome [WAS], three acute lymphoblastic leukemia [ALL], two
      AML, one severe aplastic anemia [SAA], one chronic granulomatous disease [CGD],
      and one amegakaryocytic thrombocytopenia) received allo HSCT. Their median age at
      HSCT was 255 days (142-365 days). At median follow-up of 8.7 years (2.5-17.6
      years), 26 infants remained alive, representing an overall survival rate of 76%.
      In the auto HSCT category, eight of 10 infants are long-term survivors. Late
      effects such as organ dysfunction, endocrinopathy, and secondary tumors were
      within accepted range. CONCLUSION: The survival rate of infants who receive HSCT
      is encouraging.

PMID- 25393822
TI  - Current controversies in prenatal diagnosis 3: the ethical and counseling
      implications of new genomic technologies: all pregnant women should be offered
      prenatal diagnostic genome-wide testing for prenatally identified fetal
      congenital anomalies.

PMID- 25393815
TI  - Dopamine D2 receptors preferentially regulate the development of light responses
      of the inner retina.
AB  - Retinal light responsiveness measured via electroretinography undergoes
      developmental modulation, and is thought to be critically regulated by both
      visual experience and dopamine. The primary goal of this study was to determine
      whether dopamine D2 receptors regulate the visual experience-dependent functional
      development of the retina. Accordingly, we recorded electroretinograms from wild
      type mice and mice with a genetic deletion of the gene that encodes the D2
      receptor raised under normal cyclic light conditions and constant darkness. Our
      results demonstrate that D2 receptor mutation preferentially increases the
      amplitude of the inner retinal light responses evoked by high-intensity light
      measured as oscillatory potentials in adult mice. During postnatal development,
      all three major components of electroretinograms, i.e. a-waves, b-waves, and
      oscillatory potentials, increase with age. Comparatively, D2 receptor mutation
      preferentially reduces the age-dependent increase in b-waves evoked by low
      intensity light. Light deprivation from birth reduces b-wave amplitudes and
      completely abolishes the increased amplitude of oscillatory potentials of D2
      receptor mutants. Taken together, these results demonstrate that D2 receptors
      play an important role in the activity-dependent functional development of the
      mouse retina. 

PMID- 25393823
TI  - Improving postpartum glucose screening after gestational diabetes mellitus: a
      cohort study to evaluate the multicentre IMPACT initiative.
AB  - AIMS: To evaluate a mobilization campaign, the IMPACT initiative, which included
      multidisciplinary meetings, provision of information and a systematic
      prescription of an oral glucose tolerance test to improve the rate of glucose
      screening in women with gestational diabetes mellitus in the four largest
      maternity units in our area, starting in March 2011. METHODS: We retrospectively
      compared the level of self-reported screening during the first 6 months
      postpartum of women who gave birth after having been diagnosed with gestational
      diabetes before (January 2009 to December 2010) and after the IMPACT campaign
      (April 2011 to February 2012). RESULTS: We included 961 women (589 in the period
      before and 372 in the period after the campaign was initiated) with a mean +/- SD
      age of 33.2 +/- 5.3 years and BMI of 27.8 +/- 5.3 kg/m2. Multivariate analysis,
      stratified using a propensity score in order to limit bias caused by imbalance
      between both periods, showed that the postpartum screening rate was higher after
      the campaign began (48.9 vs 33.3%, odds ratio 1.7, 95% CI 1.1-2.5; P = 0.019) and
      higher in women who received insulin treatment during pregnancy (odds ratio 2.3,
      95% CI 1.5-3.6; P < 0.001), consumed fruit and vegetables daily (odds ratio 1.6,
      95% CI 1.1-2.4; P = 0.035) and did not smoke (smoking vs non-smoking: odds ratio
      0.3, 95% CI 0.1-0.7; P = 0.01). There was no interaction between the campaign
      effect and these particular conditions. The proportion of oral glucose tolerance
      tests performed in women who underwent screening increased from 6.3 to 33.0%.
      CONCLUSIONS: The IMPACT campaign increased postpartum screening, and the use the
      oral glucose tolerance test in particular. The effect of this initiative might be
      reinforced in women who are non-daily consumers of fruit and vegetables, smokers
      and those who do not receive insulin treatment during pregnancy.

PMID- 25393824
TI  - Infrared decontamination of oregano: effects on Bacillus cereus spores, water
      activity, color, and volatile compounds.
AB  - Infrared (IR) heating, a novel technology for decontaminating oregano, was
      evaluated by investigating the reduction of inoculated Bacillus cereus spores and
      the effect on water activity (a(w)), color, and headspace volatile compounds
      after exposure to IR treatment. Conditioned oregano (a(w) 0.88) was IR-treated in
      a closed heating unit at 90 and 100  degrees C for holding times of 2 and 10 min,
      respectively. The most successful reduction in B. cereus spore numbers (5.6 log
      units) was achieved after a holding time of 10 min at 90  degrees C, while
      treatment at 100  degrees C for the same time resulted in a lower reduction
      efficiency (4.7 log units). The lower reduction at 100  degrees C was probably
      due to a reduced aw (aw 0.76) during IR treatment or possibly to the alteration
      or loss of volatile compounds possessing antimicrobial properties. The green
      color of oregano was only slightly affected, while the composition of volatile
      compounds was clearly altered by IR heating. However, two of the key aroma
      compounds, carvacrol and thymol, were only slightly affected, compared to the
      effect on the other studied compounds, indicating that the typical oregano aroma
      can likely be preserved. In conclusion, IR heating shows potential for the
      successful decontamination of oregano without severe alteration of its color or
      the key aroma compounds, carvacrol and thymol.

PMID- 25393825
TI  - Assessment of stresses in the cervical spine caused by posture and position of
      the head.
AB  - Preamble. Billions of people are using cell phone devices on the planet,
      essentially in poor posture. The purpose of this study is to assess the forces
      incrementally seen by the cervical spine as the head is tilted forward, into
      worsening posture. This data is also necessary for cervical spine surgeons to
      understand in the reconstruction of the neck. 

PMID- 25393826
TI  - Verruca plana as a complication of CO2 laser treatment: a case report.
AB  - Carbon dioxide (CO2) laser treatment is a common therapeutic modality for many
      dermatologic conditions. It uses a high energy, infrared beam of light, which
      selectively targets water-containing tissue resulting in controlled ablative
      resurfacing. This modality, however, can manifest significant cosmetic side
      effects. Here we report a case of verruca plana manifesting as a response to CO2
      laser treatment. A 74-year-old female with recent Mohs surgery for a basal cell
      carcinoma, presented for full-face-fractionated CO2 treatment to address her
      surgical scars in addition to treating her mild diffuse actinic damage. Six weeks
      post treatment, the patient developed erythematous thin plaques over the areas
      that had been treated. Histology was consistent with verruca plana. Lesions
      showed mild improvement with topical tretinoin. Verruca plana are benign and
      typically self-limited; however, they can present a significant cosmetic burden
      to patients and are an important complication to consider when performing
      elective cosmetic procedures. 

PMID- 25393827
TI  - Cobalt-catalyzed C(sp(2))-H alkoxylation of aromatic and olefinic carboxamides.
AB  - The cobalt-catalyzed alkoxylation of C(sp(2) )?H bonds in aromatic and olefinic
      carboxamides has been developed. The reaction proceeded under mild conditions in
      the presence of Co(OAc)2 ?4H2 O as the catalyst and tolerates a wide range of
      both alcohols and benzamide substrates, including even olefinic carboxamides. In
      addition, this reaction is the first example of the direct alkoxylation of
      alkenes through C?H bond activation. 

PMID- 25393830
TI  - Identifying splicing regulatory elements with de Bruijn graphs.
AB  - Splicing regulatory elements (SREs) are short, degenerate sequences on pre-mRNA
      molecules that enhance or inhibit the splicing process via the binding of
      splicing factors, proteins that regulate the functioning of the spliceosome.
      Existing methods for identifying SREs in a genome are either experimental or
      computational. Here, we propose a formalism based on de Bruijn graphs that
      combines genomic structure, word count enrichment analysis, and experimental
      evidence to identify SREs found in exons. In our approach, SREs are not
      restricted to a fixed length (i.e., k-mers, for a fixed k). As a result, we
      identify 2001 putative exonic enhancers and 3080 putative exonic silencers for
      human genes, with lengths varying from 6 to 15 nucleotides. Many of the predicted
      SREs overlap with experimentally verified binding sites. Our model provides a
      novel method to predict variable length putative regulatory elements
      computationally for further experimental investigation.

PMID- 25393832
TI  - Measuring nursing informatics competencies of practicing nurses in Korea: Nursing
      Informatics Competencies Questionnaire.
AB  - Informatics competencies are a necessity for contemporary nurses. However, few
      researchers have investigated informatics competencies for practicing nurses. A
      full set of Informatics competencies, an instrument to measure these
      competencies, and potential influencing factors have yet to be identified for
      practicing nurses. The Nursing Informatics Competencies Questionnaire was
      designed, tested for psychometrics, and used to measure beginning and experienced
      levels of practice. A pilot study using 54 nurses ensured item comprehension and
      clarity. Internal consistency and face and content validity were established. A
      cross-sectional survey was then conducted on 230 nurses in Seoul, Korea, to
      determine construct validity, describe a complete set of informatics
      competencies, and explore possible influencing factors on existing informatics
      competencies. Principal components analysis, descriptive statistics, and multiple
      regression were used for data analysis. Principal components analysis gives
      support for the Nursing Informatics Competencies Questionnaire construct
      validity. Survey results indicate that involvement in a managerial position and
      self-directed informatics-related education may be more influential for improving
      informatics competencies, whereas general clinical experience and workplace
      settings are not. This study provides a foundation for understanding how
      informatics competencies might be integrated throughout nurses' work lives and
      how to develop appropriate strategies to support nurses in their informatics
      practice in clinical settings.

PMID- 25393831
TI  - Synthesis of bicyclic guanidines via cascade hydroamination/Michael additions of
      mono-N-acryloylpropargylguanidines.
AB  - A cascade silver(I)-catalyzed hydroamination/Michael addition sequence has been
      developed to deliver highly substituted bicyclic guanidines. This transformation
      gives rise to geometrically and constitutionally stable ene-guanidines and
      generates a remote stereocenter with moderate to high diastereoselectivity. 

PMID- 25393833
TI  - Utilizing social networking sites to promote adolescents' health: a pragmatic
      review of the literature.
AB  - Social networking site use has exploded among youth in the last few years and is
      being adapted as an important tool for healthcare interventions and serving as a
      platform for adolescents to gain access to health information. The aim of this
      study was to examine the strengths, weaknesses, and best practices of utilizing
      Facebook in adolescent health promotion and research via pragmatic literature
      review. We also examine how sites can facilitate ethically sound healthcare for
      adolescents, particularly at-risk youth. We conducted a literature review of
      health and social sciences literature from the past 5 years related to adolescent
      health and social network site use. Publications were grouped by shared content
      then categorized by themes. Five themes emerged: access to healthcare
      information, peer support and networking, risk and benefits of social network
      site use in care delivery, overcoming technological barriers, and social network
      site interventions. More research is needed to better understand how such Web
      sites can be better utilized to provide access to adolescents seeking healthcare.
      Given the broad reach of social network sites, all health information must be
      closely monitored for accurate, safe distribution. Finally, consent and privacy
      issues are omnipresent in social network sites, which calls for standards of
      ethical use. 

PMID- 25393834
TI  - Mosquito surveillance revealed lagged effects of mosquito abundance on mosquito
      borne disease transmission: a retrospective study in Zhejiang, China.
AB  - Mosquito-borne diseases (MBDs) are still threats to public health in Zhejiang. In
      this study, the associations between the time-lagged mosquito capture data and
      MBDs incidence over five years were used to examine the potential effects of
      mosquito abundance on patterns of MBDs epidemiology in Zhejiang during 2008-2012.
      Light traps were used to collect adult mosquitoes at 11 cities. Correlation tests
      with and without time lag were performed to investigate the correlations between
      MBDs incidence rates and mosquito abundance by month. Selected MBDs consisted of
      Japanese encephalitis (JE), dengue fever (DF) and malaria. A Poisson regression
      analysis was performed by using a generalized estimating equations (GEE)
      approach, and the most parsimonious model was selected based on the quasi
      likelihood based information criterion (QICu). We identified five mosquito
      species and the constituent ratio of Culex pipiens pallens, Culex
      tritaeniorhynchus, Aedes albopictus, Anopheles sinensis and Armigeres subalbatus
      was 66.73%, 21.47%, 6.72%, 2.83% and 2.25%, respectively. The correlation
      analysis without and with time lag showed that Culex mosquito abundance at a lag
      of 0 or 1 month was positively correlated with JE incidence during 2008-2012, Ae.
      albopictus abundance at a lag of 1 month was positively correlated with DF
      incidence in 2009, and An. sinensis abundance at a lag of 0-2 months was
      positively correlated with malaria incidence during 2008-2010. The Poisson
      regression analysis showed each 0.1 rise of monthly mosquito abundance
      corresponded to a positive increase of MBD cases for the period of 2008-2012. The
      rise of mosquito abundance with a lag of 0-2 months increased the risk of human
      MBDs infection in Zhejiang. Our study provides evidence that mosquito monitoring
      could be a useful early warning tool for the occurrence and transmission of MBDs.

PMID- 25393835
TI  - Vintage progressive outer retinal necrosis.

PMID- 25393837
TI  - Intercrop movement of convergent lady beetle, Hippodamia convergens (Coleoptera:
      Coccinellidae), between adjacent cotton and alfalfa.
AB  - A 2-year study was conducted to characterize the intercrop movement of convergent
      lady beetle, Hippodamia convergens Guerin-Meneville (Coleoptera: Coccinellidae)
      between adjacent cotton and alfalfa. A dual protein-marking method was used to
      assess the intercrop movement of the lady beetles in each crop. In turns field
      collected lady beetles in each crop were assayed by protein specific ELISA to
      quantify the movement of beetles between the crops. Results indicated that a high
      percentage of convergent lady beetles caught in cotton (46% in 2008; 56% in 2009)
      and alfalfa (46% in 2008; 71% in 2009) contained a protein mark, thus indicating
      that convergent lady beetle movement was largely bidirectional between the
      adjacent crops. Although at a much lower proportion, lady beetles also showed
      unidirectional movement from cotton to alfalfa (5% in 2008 and 6% in 2009) and
      from alfalfa to cotton (9% in 2008 and 14% in 2009). The season-long
      bidirectional movement exhibited by the beetles was significantly higher in
      alfalfa than cotton during both years of the study. The total influx of lady
      beetles (bidirectional and unidirectional combined) was significantly higher in
      alfalfa compared with that in cotton for both years. While convergent lady
      beetles moved between adjacent cotton and alfalfa, they were more attracted to
      alfalfa when cotton was not flowering and/or when alfalfa offered more
      opportunities for prey. This study offers much needed information on intercrop
      movement of the convergent lady beetle that should facilitate integrated pest
      management decisions in cotton utilizing conservation biological control. 

PMID- 25393836
TI  - Diabetes, glucose metabolism, and glaucoma: the 2005-2008 National Health and
      Nutrition Examination Survey.
AB  - BACKGROUND: Diabetes may affect vascular autoregulation of the retina and optic
      nerve and may be associated with an increased risk of glaucoma,but the
      association of prediabetes, insulin resistance, markers of glucose metabolismwith
      glaucoma has not beenevaluated in general population samples. OBJECTIVE: To
      examine the relation between diabetes, pre-diabetes, metabolic syndrome and its
      components and the levels of fasting glucose, HbA1c and HOMA-IR with the
      prevalence of glaucoma in the general U.S. population. METHODS: Cross-sectional
      study of 3,299 adult men and women from the 2005-2008 National Health and
      NutritionExamination Survey (NHANES). The presence of diabetes, prediabetes, the
      metabolic syndrome and its individual components and biomarkers of glucose
      metabolisms were based on standardized questionnaire and physical exam data and
      laboratory tests. The history of glaucoma was assessed through questionnaire
      during the home interview. RESULTS: Diabetes was strongly associated with
      prevalent glaucoma.In fully adjusted models, the odds ratiofor glaucoma comparing
      participants with diabetes with participants in the reference group with neither
      pre-diabetes nor diabetes was 2.12 (95% CI: 1.23, 3.67). The corresponding odd
      ratio comparing participants with pre-diabetes to those in the reference group
      was 1.01 (95% CI: 0.57, 1.82). Patients with 5 or more years of diabetes duration
      hadan OR for glaucoma of 3.90 (95% CI: 1.63, 9.32) compared with patients with <5
      years of diabetes duration. We also found a hockey-stick shaped associations
      between biomarkers of glucose metabolisms and the prevalence of glaucoma.
      CONCLUSIONS: Diabetes was associated with higher risk of glaucoma. Participants
      without diabetes but at the higher levels of fasting glucose, fasting insulin,
      HbA1c and HOMA-IR spectrum may also be at greater risk of glaucoma.

PMID- 25393838
TI  - Patient-specific risk factors of adverse drug events in adult inpatients -
      evidence detected using the Global Trigger Tool method.
AB  - AIMS AND OBJECTIVES: To identify the prevalence, preventability, and severity of
      adverse drug events in randomly selected adult hospital inpatients, and to study
      the association between adverse drug events and patient-specific factors.
      BACKGROUND: Adverse drug events represent one of the major concerns in patient
      safety. DESIGN: A retrospective record review. METHODS: The study was conducted
      in an 800-bed university hospital in Finland within a 12-month period.
      Retrospective reviews of randomly selected discharged patients' (n = 463) records
      using the Global Trigger Tool method were undertaken. The prevalence,
      preventability, and severity of adverse drug events were studied, and the
      association between patient-specific factors and adverse drug events were
      examined using a binary logistic regression model and Pearson's chi-squared
      tests. RESULTS: A total of 180 adverse drug events were detected in 125 (27%)
      patients, of which 74 (41.1%) were preventable, and 94.4% caused temporary harm.
      An abnormal level of potassium in the blood was the most frequent adverse drug
      event (n = 37). The risk of adverse drug events increased with the length of
      hospital stay and the increased number of drugs patients used. The patients with
      coronary diseases (n = 130) had a 2.5 times higher risk of experiencing adverse
      drug events. In addition, the risk of adverse drug events during hospitalisation
      increased together with the co-morbidity of patients. CONCLUSIONS: Adverse drug
      events were experienced by a quarter of inpatients, while severe adverse drug
      events were rare. The risk of adverse drug events increased with patients'
      prolonged hospital stay, polypharmacy, and morbidity. In addition, information of
      the usefulness of the Global Trigger tool can be used for future development of
      the method. RELEVANCE TO CLINICAL PRACTICE: Patient-specific risk factors were
      identified using the Global Trigger Tool method revealing that more efficient
      monitoring of inpatients with these risk factors may be profitable for decreasing
      adverse drug events.

PMID- 25393840
TI  - Copper-catalyzed aerobic C - C bond cleavage of lactols with N-hydroxy
      phthalimide for synthesis of lactones.
AB  - The transformation of cyclic hemiacetals (lactols) into lactones has been
      achieved by Cu-catalyzed aerobic C?C bond cleavage in the presence of N-hydroxy
      phthalimide (NHPI). The present process is composed of a multistep sequence
      including a) formation of exo-cyclic enol ethers by dehydration; b) addition of
      phthalimide N-oxyl radical to the enol ethers followed by trapping of the
      resulting C-radicals with molecular oxygen to form peroxy radicals; c) reductive
      generation of oxy radicals and subsequent beta-radical fragmentation to generate
      lactones. 

PMID- 25393841
TI  - A systematic evaluation of the use of physiologically based pharmacokinetic
      modeling for cross-species extrapolation.
AB  - Transfer of knowledge along the different phases of drug development is a
      fundamental process in pharmaceutical research. In particular, cross-species
      extrapolation between different laboratory animals and further on to first-in
      human trials is challenging because of the uncertain comparability of
      physiological processes. Physiologically based pharmacokinetic (PBPK) modeling
      allows translation of mechanistic knowledge from one species to another by
      specifically considering physiological and biochemical differences in between. We
      here evaluated different knowledge-driven approaches for cross-species
      extrapolation by systematically incorporating specific model parameter domains of
      a target species into the PBPK model of a reference species. Altogether, 15
      knowledge-driven approaches were applied to murine and human PBPK models of 10
      exemplary drugs resulting in 300 different extrapolations. Statistical analysis
      of the quality of the different extrapolations revealed not only species-specific
      physiology as the key determinant in cross-species extrapolation but also
      identified a synergistic effect when considering both kinetic rate constants and
      gene expression profiles of relevant enzymes and transporters. Moreover, we show
      that considering species-specific physiology, plasma protein binding, enzyme and
      transport kinetics, as well as tissue-specific gene expression profiles in PBPK
      modeling increases accuracy of cross-species extrapolations and thus supports
      first-in-human trials based on prior preclinical knowledge.

PMID- 25393842
TI  - Identification, quantification, and sensory characterization of steviol
      glycosides from differently processed Stevia rebaudiana commercial extracts.
AB  - Stevia rebaudiana is known for its sweet-tasting ent-kaurene diterpenoid
      glycosides. Several manufacturing strategies are currently employed to obtain
      Stevia sweeteners with the lowest possible off-flavors. The chemical composition
      of four commercial S. rebaudiana extracts, obtained by different technologies,
      was characterized using UHPLC-ESI-MS(n). The composition of one of the ethanol
      crystallized extracts (EC2) was entirely rebaudioside A, whereas the
      enzymatically modified (EM) extract contained the lowest concentration of this
      compound (2.7 mg/100 mg). The membrane-purified (MP) extract had the highest
      content of minor natural steviol glycosides (23.7 mg/100 mg total extract) versus
      an average of 2.4 mg/100 mg total extract for the EC samples. Thirteen trained
      panelists evaluated sweetness, bitterness, licorice, and metallic attributes of
      all four extracts. The highest licorice intensity (p <= 0.05) was found for MP.
      Both samples EC1 and EC2, despite their different chemical compositions, showed
      no significant differences in sensory perception. 

PMID- 25393839
TI  - Changes in corticostriatal connectivity during reinforcement learning in humans.
AB  - Many computational models assume that reinforcement learning relies on changes in
      synaptic efficacy between cortical regions representing stimuli and striatal
      regions involved in response selection, but this assumption has thus far lacked
      empirical support in humans. We recorded hemodynamic signals with fMRI while
      participants navigated a virtual maze to find hidden rewards. We fitted a
      reinforcement-learning algorithm to participants' choice behavior and evaluated
      the neural activity and the changes in functional connectivity related to trial
      by-trial learning variables. Activity in the posterior putamen during choice
      periods increased progressively during learning. Furthermore, the functional
      connections between the sensorimotor cortex and the posterior putamen
      strengthened progressively as participants learned the task. These changes in
      corticostriatal connectivity differentiated participants who learned the task
      from those who did not. These findings provide a direct link between changes in
      corticostriatal connectivity and learning, thereby supporting a central
      assumption common to several computational models of reinforcement learning.

PMID- 25393843
TI  - Fourfold alkoxy-substituted [2.2.2]paracyclophane-1,9,17-trienes-ROMP into PPVs
      with unusual topologies.
AB  - The synthesis of two 4,7,12,15-tetrakisalkoxy-substituted [2.2.2]-paracyclophane
      1,9,17-trienes and their polymerization employing ring opening metathesis
      polymerization (ROMP) using Ru-carbenes (third-generation Grubbs catalyst) is
      reported. Phenylene ethynylene trimers are reduced via a Grignard reagent,
      followed by an intramolecular McMurry cyclization to give the cyclophenes. The
      cyclophenes are polymerized into soluble poly(para-phenylene vinylene)s (PPV),
      which are analyzed in solution by NMR, UV-vis, and fluorescence spectroscopy.
      They are spin coated into amorphous, fluorescent thin films, and investigated by
      optical spectroscopy and cyclic voltammetry.

PMID- 25393844
TI  - 3D printing of reduced graphene oxide nanowires.
AB  - 3D printing of reduced graphene oxide (rGO) nanowires is realized at room
      temperature by local growth of GO at the meniscus formed at a micropipette tip
      followed by reduction of GO by thermal or chemical treatment. 3D rGO nanowires
      with diverse and complicated forms are successfully printed, demonstrating their
      ability to grow in any direction and at the selected sites. 

PMID- 25393845
TI  - Purification of equine chorionic gonadotropin (eCG) using magnetic ion exchange
      adsorbents in combination with high-gradient magnetic separation.
AB  - Current purification of the glycoprotein equine chorionic gonadotropin (eCG) from
      horse serum includes consecutive precipitation steps beginning with
      metaphosphoric acid pH fractionation, two ethanol precipitation steps, and
      dialysis followed by a numerous of fixed-bed chromatography steps up to the
      specific activity required. A promising procedure for a more economic
      purification procedure represents a simplified precipitation process requiring
      only onethird of the solvent, followed by the usage of magnetic ion exchange
      adsorbents employed together with a newly designed 'rotor-stator' type High
      Gradient Magnetic Fishing (HGMF) system for large-scale application, currently up
      to 100 g of magnetic adsorbents. Initially, the separation process design was
      optimized for binding and elution conditions for the target protein in mL scale.
      Subsequently, the magnetic filter for particle separation was characterized.
      Based on these results, a purification process for eCG was designed consisting of
      (i) pretreatment of the horse serum; (ii) binding of the target protein to
      magnetic ion exchange adsorbents in a batch reactor; (iii) recovery of loaded
      functionalized adsorbents from the pretreated solution using HGMF; (iv) washing
      of loaded adsorbents to remove unbound proteins; (v) elution of the target
      protein. Finally, the complete HGMF process was automated and conducted with
      either multiple single-cycles or multicycle operation of four sequential cycles,
      using batches of pretreated serum of up to 20 L. eCG purification with yields of
      approximately 53% from single HGMF cycles and up to 80% from multicycle
      experiments were reached, with purification and concentration factors of around
      2,500 and 6.7, respectively.

PMID- 25393846
TI  - Outcome of assisted reproductive technology (ART) and subsequent self-reported
      life satisfaction.
AB  - OBJECTIVE: To compare life satisfaction between women with successful or
      unsuccessful outcome after assisted reproductive treatment (ART) by taking into
      account the time since the last ART. DESIGN: Cohort study. SETTING: Tertiary
      hospital. PATIENTS: A total of 987 consecutive women who had undergone ART during
      1996-2007 were invited and altogether 505 women participated in the study.
      INTERVENTIONS: A postal enquiry with a life satisfaction scale. MAIN OUTCOME
      MEASURE: Self-reported life satisfaction in respect to the time since the last
      ART. RESULTS: In general, women who achieved a live birth after ART had a
      significantly higher life satisfaction than those who had unsuccessful ART,
      especially when compared in the first three years. The difference disappeared in
      the time period of 6-9 years after ART. The unsuccessfully treated women who had
      a child by some other means before or after the unsuccessful ART had comparable
      life satisfaction with successfully treated women even earlier. CONCLUSIONS: Even
      if unsuccessful ART outcome is associated with subsequent lower level of life
      satisfaction, it does not seem to threaten the long-term wellbeing.

PMID- 25393847
TI  - Multicenter retrospective analysis regarding the clinical manifestations and
      treatment results in patients with hairy cell leukemia: twenty-four year Turkish
      experience in cladribine therapy.
AB  - In this multicenter retrospective analysis, we aimed to present clinical,
      laboratory and treatment results of 94 patients with Hairy cell leukemia
      diagnosed in 13 centers between 1990 and 2014. Sixty-six of the patients were
      males and 28 were females, with a median age of 55. Splenomegaly was present in
      93.5% of cases at diagnosis. The laboratory findings that came into prominence
      were pancytopenia with grade 3 bone marrow fibrosis. Most of the patients with an
      indication for treatment were treated with cladribine as first-line treatment.
      Total and complete response of cladribine was 97.3% and 80.7%. The relapse rate
      after cladribine was 16.6%, and treatment related mortality was 2.5%. Most
      preferred therapy (95%) was again cladribine at second-line, and third line with
      CR rate of 68.4% and 66.6%, respectively. The 28-month median OS was 91.7% in all
      patients and 25-month median OS 96% for patients who were given cladribine as
      first-line therapy. In conclusion, the first multicenter retrospective Turkish
      study where patients with HCL were followed up for a long period has revealed
      demographic characteristics of patients with HCL, and confirmed that cladribine
      treatment might be safe and effective in a relatively large series of the Turkish
      study population.

PMID- 25393848
TI  - Dual-source CT imaging to plan transcatheter aortic valve replacement: accuracy
      for diagnosis of obstructive coronary artery disease.
AB  - PURPOSE: To assess the accuracy of computed tomographic (CT) examinations
      performed for the purpose of transcatheter aortic valve replacement (TAVR)
      planning to diagnose obstructive coronary artery disease (CAD). MATERIALS AND
      METHODS: With institutional review board approval, waivers of informed consent,
      and in compliance with HIPAA, 100 consecutive TAVR candidates (61 men, mean age
      79.6 years +/- 9.9) who underwent both TAVR planning CT (with a dual-source CT
      system) and coronary catheter (CC) angiographic imaging were retrospectively
      analyzed. At both modalities, the presence of stenosis in the native coronary
      arteries was assessed. Additionally, all coronary bypass grafts were rated as
      patent or occluded. With CC angiographic imaging as the reference standard, the
      accuracy of CT for lesion detection on a per-vessel and per-patient basis was
      calculated. The accuracy of CT for the assessment of graft patency was also
      analyzed. RESULTS: For per-vessel and per-patient analysis for the detection of
      stenosis that was 50% or more in the native coronary arteries, CT imaging had,
      respectively, 94.4% and 98.6% sensitivity, 68.4% and 55.6% specificity, 94.7% and
      93.8% negative predictive value (NPV), and 67.0% and 85.7% positive predictive
      value. Per-patient sensitivity of stenosis 50% or greater with CT for greater
      than 70% stenosis at CC angiographic imaging was 100%. All 12 vessels in which
      percutaneous coronary intervention was performed were correctly identified as
      demonstrating stenosis 50% or greater with CT. There was agreement between CT and
      CC angiographic imaging regarding graft patency in 114 of 115 grafts identified
      with CC angiographic imaging. CONCLUSION: TAVR planning CT has high sensitivity
      and NPV in excluding obstructive CAD. An additional preprocedural CC angiographic
      examination may not be required in TAVR candidates with a CT examination that
      does not show obstructive CAD.

PMID- 25393850
TI  - When should fQRS be evaluated as a noninvasive prognostic marker in patients
      undergoing primary PCI with STEMI?

PMID- 25393849
TI  - Targeted screening of individuals at high risk for pancreatic cancer: results of
      a simulation model.
AB  - PURPOSE: To identify when, from the standpoint of relative risk, magnetic
      resonance (MR) imaging-based screening may be effective in patients with a known
      or suspected genetic predisposition to pancreatic cancer. MATERIALS AND METHODS:
      The authors developed a Markov model of pancreatic ductal adenocarcinoma (PDAC).
      The model was calibrated to National Cancer Institute Surveillance, Epidemiology,
      and End Results registry data and informed by the literature. A hypothetical
      screening strategy was evaluated in which all population individuals underwent
      one-time MR imaging screening at age 50 years. Screening outcomes for individuals
      with an average risk for PDAC ("base case") were compared with those for
      individuals at an increased risk to assess for differential benefits in
      populations with a known or suspected genetic predisposition. Effects of varying
      key inputs, including MR imaging performance, surgical mortality, and screening
      age, were evaluated with a sensitivity analysis. RESULTS In the base case,
      screening resulted in a small number of cancer deaths averted (39 of 100 000 men,
      38 of 100 000 women) and a net decrease in life expectancy (-3 days for men, -4
      days for women), which was driven by unnecessary pancreatic surgeries associated
      with false-positive results. Life expectancy gains were achieved if an
      individual's risk for PDAC exceeded 2.4 (men) or 2.7 (women) times that of the
      general population. When relative risk increased further, for example to 30 times
      that of the general population, averted cancer deaths and life expectancy gains
      increased substantially (1219 of 100 000 men, life expectancy gain: 65 days; 1204
      of 100 000 women, life expectancy gain: 71 days). In addition, results were
      sensitive to MR imaging specificity and the surgical mortality rate. CONCLUSION:
      Although PDAC screening with MR imaging for the entire population is not
      effective, individuals with even modestly increased risk may benefit.

PMID- 25393851
TI  - Discovery of BI 207524, an indole diamide NS5B thumb pocket 1 inhibitor with
      improved potency for the potential treatment of chronic hepatitis C virus
      infection.
AB  - The development of interferon-free regimens for the treatment of chronic HCV
      infection constitutes a preferred option that is expected in the future to
      provide patients with improved efficacy, better tolerability, and reduced risk
      for emergence of drug-resistant virus. We have pursued non-nucleoside NS5B
      polymerase allosteric inhibitors as combination partners with other direct acting
      antivirals (DAAs) having a complementary mechanism of action. Herein, we describe
      the discovery of a potent follow-up compound (BI 207524, 27) to the first thumb
      pocket 1 NS5B inhibitor to demonstrate antiviral activity in genotype 1 HCV
      infected patients, BILB 1941 (1). Cell-based replicon potency was significantly
      improved through electronic modulation of the pKa of the carboxylic acid function
      of the lead molecule. Subsequent ADME-PK optimization lead to 27, a predicted low
      clearance compound in man. The preclinical profile of inhibitor 27 is discussed,
      as well as the identification of a genotoxic metabolite that led to the
      discontinuation of the development of this compound. 

PMID- 25393852
TI  - Reproductive physiology and ovarian folliculogenesis examined via 1H-NMR
      metabolomics signatures: a comparative study of large and small follicles in
      three mammalian species (Bos taurus, Sus scrofa domesticus and Equus ferus
      caballus).
AB  - The aim of this study was to characterize the composition of follicular fluid
      (FF) collected from the small and large follicles of three mammalian species, Bos
      taurus, Sus scrofa domesticus, and Equus ferus caballus, that display distinct
      ovulatory properties. For each species, five large FF samples and five small FF
      samples were analyzed using 1H-NMR spectroscopy. The FF metabolic profiles of the
      three species were very distinct. In cows and mares, the metabolic profiles of
      large FF and small FF were also very distinct. The concentrations of seventeen
      identified metabolites differed significantly between the sample groups. In
      mares, fourteen metabolites were found at much greater concentrations in large FF
      than in small FF (p<0.05). In cows, four metabolites differed in concentration
      between the large FF and small FF samples (p<0.05). A common feature of the
      monovulatory species was that the concentrations of alpha- and beta-glucose were
      much greater in large FF compared with small FF (p<0.05). Sow FF was
      characterized by the apparent absence of citrate (detected in cow and mare FF),
      and the presence of succinate (not detected in cow and mare FF). Another obvious
      difference between species was the concentration of lactate, which was minimal in
      mare FF compared with cow and sow FF (p<0.05). The findings provide valuable
      insights into reproductive physiology broadly, and indicate that the activities
      of central metabolic enzymes differ enormously between these species. Future
      investigations into species-specific differences in follicle metabolism would
      increase our understanding of the processes critical to folliculogenesis and the
      acquisition of oocyte developmental competence.

PMID- 25393854
TI  - Feasibility of fast track discharge in breast cancer patients undergoing
      definitive surgery and impact on quality of life: a prospective study from
      tertiary care center in India.
AB  - OBJECTIVE: To evaluate the feasibility and impact of fast track discharge in
      patients undergoing definitive breast cancer surgery. METHODS: One hundred six
      breast cancer patients older than 20 years of age were assigned to undergo
      definitive breast cancer surgery. It was ensured that enrolled patients had a
      ready access to hospital, reasonable home circumstances. They were assessed by
      using post-anesthesia discharge scoring system (PADSS) for fast track discharge.
      Quality of life both in preoperative and postoperative period was assessed by
      Functional Assessment of Cancer Therapy-Breast cancer version 4 (FACT-B4)
      questionnaires. RESULT: Overall 90 patients (84.9%) were fit for fast track
      discharge. Eighty-nine patients (83.96%) were successfully discharged within 48
      hr. One patient (0.94%) could not be discharged despite being fit as she was of
      concern that it would put too much responsibility on the family. Mean duration of
      postoperative hospital stay in patients fit for fast track surgery was 42.27 +/-
      5.73 hr with a median of 44 hr. All patients undergoing breast conservation could
      be discharged on fast track basis with a mean postoperative hospital stay of
      32.12 hr. CONCLUSION: Fast track discharges in breast cancer patients after
      definitive surgery are feasible in Indian setting.

PMID- 25393855
TI  - One pot, two phases: individual orthorhombic and face-centered cubic ZnSnO3
      obtained synchronously in one solution.
AB  - Many modern technologies rely on the functional materials that are subject to
      their phase purity. The topic of obtaining pure crystals from the concomitant
      allotropes is ever before the eyes of numerous researchers. Here we adopt a
      template-inducing route and obtain the isolated allotropes located in the
      appointed regions in the same reaction system. As a typical example, well-defined
      individual face-centered cubic and orthorhombic ZnSnO3 crystals were successfully
      synthesized assisted by a ZnO inducing template or without it in an identical
      solution, respectively. And the different growing mechanisms of the ZnSnO3
      allotropes were also proposed, which takes a pivotal step toward the realization
      of allotropes dividing. Moreover, the two individual pure-phased ZnSnO3
      allotropes obtained in one reaction system exhibit porous microspherical
      morphologies constructed by the tiny nanograins, resulting in their high
      sensitivities to ethanol with fast response and recovery and good selectivity and
      stability. 

PMID- 25393853
TI  - Dysregulated B cell expression of RANKL and OPG correlates with loss of bone
      mineral density in HIV infection.
AB  - HIV infection is associated with high rates of osteopenia and osteoporosis, but
      the mechanisms involved are unclear. We recently reported that bone loss in the
      HIV transgenic rat model was associated with upregulation of B cell expression of
      the key osteoclastogenic cytokine receptor-activator of NF-kappaB ligand (RANKL),
      compounded by a simultaneous decline in expression of its physiological
      moderator, osteoprotegerin (OPG). To clinically translate these findings we
      performed cross-sectional immuno-skeletal profiling of HIV-uninfected and
      antiretroviral therapy-naive HIV-infected individuals. Bone resorption and
      osteopenia were significantly higher in HIV-infected individuals. B cell
      expression of RANKL was significantly increased, while B cell expression of OPG
      was significantly diminished, conditions favoring osteoclastic bone resorption.
      The B cell RANKL/OPG ratio correlated significantly with total hip and femoral
      neck bone mineral density (BMD), T- and/or Z-scores in HIV infected subjects, but
      revealed no association at the lumbar spine. B cell subset analyses revealed
      significant HIV-related increases in RANKL-expressing naive, resting memory and
      exhausted tissue-like memory B cells. By contrast, the net B cell OPG decrease in
      HIV-infected individuals resulted from a significant decline in resting memory B
      cells, a population containing a high frequency of OPG-expressing cells,
      concurrent with a significant increase in exhausted tissue-like memory B cells, a
      population with a lower frequency of OPG-expressing cells. These data validate
      our pre-clinical findings of an immuno-centric mechanism for accelerated HIV
      induced bone loss, aligned with B cell dysfunction. 

PMID- 25393856
TI  - Acute kidney injury in schistosomiasis: a retrospective cohort of 60 patients in
      Brazil.
AB  - The aim of this study is to investigate renal involvement in schistosomiasis.
      This is a retrospective cohort of 60 consecutive patients with schistosomiasis
      admitted to a university hospital in Maceio, Brazil. The patients were divided
      into 2 groups: patients with and without acute kidney injury (AKI) according to
      the RIFLE criteria. We compared the groups for differences in clinical
      manifestations and laboratory tests. Patients' mean age was 58 +/- 16 yr, and
      56.7% were female. The average length of hospital stay was 16.4 +/- 12.1 days.
      Patients with hypertension and diabetes were 35% and 21.7% respectively. The main
      clinical symptoms and signs presented were ascites (86.7%), splenomegaly (80%),
      and hepatomegaly (63.3%). Current or previous history of upper gastrointestinal
      bleeding was found in 45% of patients, esophageal varices on endoscopy were
      present in 92%, and periportal fibrosis on ultrasound examination in 81% of
      patients. AKI incidence was 43.3% during hospital stay. Mean age and length of
      hospitalization were higher in the AKI group. Diuretic use, such as furosemide
      and spironolactone, ascites, and AST levels were also associated with AKI. Death
      occurred in 5 cases (8.5%), 4 of them in the AKI group. The classifications Child
      Pugh score (CHILD) and Model for End-Stage Liver Disease (MELD), used to assess
      the severity and prognosis of chronic liver disease, presented higher scores
      among patients with AKI (CHILD: 9.5 +/- 1.5 vs. 8.4 +/- 1.7, P = 0.02; MELD: 19
      +/- 5.8 vs. 13 +/- 3.9, P < 0.001). Renal dysfunction is an important feature of
      schistosomiasis, which is associated with significant morbidity and possible
      increased mortality. Further studies are necessary to establish the mechanisms
      through which schistosomiasis can lead to renal dysfunction. 

PMID- 25393857
TI  - [Space medicine].

PMID- 25393858
TI  - [Study of the polymorphism R353Q in the coagulation factor VII gene and the N700S
      in the thrombospondin-1 gene in young patients with acute myocardial infarction].
AB  - BACKGROUND: Acute myocardial infarction is the first cause of morbidity and
      mortality in the world, resulting in the combination of genetic and environmental
      factors. It has been postulated that the R353Q polymorphism of the coagulation
      FVII gene represents a protective factor for acute myocardial infarction, whereas
      the N700S polymorphism in the thrombospondin-1 gene is associated with an
      increased risk for acute myocardial infarction; however, the results are still
      contradicted. The objective of the study was to examine the possible association
      of the FVII R353Q and N700S polymorphism and acute myocardial infarction in
      Mexican patients with acute myocardial infarction younger than 45 years old.
      METHODS: Case-control study that included 252 patients who were diagnosed with
      acute myocardial infarction and 252 apparently healthy, age- and gender-matched
      individuals without a history of coronary artery disease. R353Q and N700S
      polymorphisms were determined in all participants by PCR-RFLP. RESULTS: There was
      no statistical significant difference in genotype distribution (p = 0.06) between
      the acute myocardial infarction and control groups. Also, there was a similar
      genotype distribution of N700S polymorphism between stroke and control groups (p
      = 0.50). Hypertension, diabetes mellitus, family history of coronary disease and
      dyslipidemia represented independent risk factors for acute myocardial
      infarction. CONCLUSIONS: Polymorphisms R353Q and N700S do not represent a
      protective or risk factor for acute myocardial infarction in young Mexican
      individuals.

PMID- 25393859
TI  - [Determination of von Willebrand factor multimers in Mexican population].
AB  - BACKGROUND: Von Willebrand disease is an inherited disease in which the
      structure, function, and concentration of von Willebrand factor are altered, as
      well as the platelet von Willebrand factor endothelium interaction. In Mexico
      there are no epidemiological records of the disease. Only a few isolated studies
      have been reported from the clinical and hematological standpoint. METHODS: We
      studied 155 Mexican Mestizos: 75 with presumptive diagnosis of von Willebrand
      disease, 15 with suspected diagnosis ofhemophilia A and 65 healthy donors
      (controls). Basic coagulation tests, special tests and classification test
      (analysis of multimeric composition) were carried out. RESULTS: There were 15
      patients with clinical diagnosis of hemophilia A, 75 patients with suspected von
      Willebrand disease of which 50 were diagnosed as the following types and
      subtypes: Type 1 (62%), Type 2 (22%) [subtypes: 2A (14%), 2B (2%), and 2N (6%)]
      and Type 3 (16%). CONCLUSION: It has been reported that analysis of von
      Willebrand factor is a method that meets the characteristics for the diagnosis of
      von Willebrand disease. It is necessary to implement this methodology to study
      and improve the specific diagnoses.

PMID- 25393860
TI  - [Seroprevalence of antinuclear antibodies in blood donors in the Yaqui Valley].
AB  - BACKGROUND: Antinuclear antibodies are immunoglobulins that recognize autologous
      nuclear and cytoplasmic cellular components. In healthy persons they are not
      associated with autoimmune disease. However, they may be related to an immune
      risk phenotype that has not been sufficiently studied. We undertook this study to
      examine the presence of antinuclear antibodies in serum from blood donors.
      METHODS: Cross-sectional study on 379 blood donors between 18 and 65 years old.
      Serum for the presence of antinuclear antibodies by indirect immunofluorescence
      in HEp-2 cells was analyzed. The prevalence and pattern of expression were
      compared with age, gender, and history of rheumatic or thyroid disease. RESULTS:
      Prevalence of antinuclear antibodies in the study population was 13%. Most of the
      positive subjects were between 21 and 40 years old. Male gender expressed a
      greater proportion of positivity (11%) than females (2%). Likewise, 82% of males
      had low titers (1:80) and nucleolar type in 66% of cases (OR = 10.66 [1.83 to
      62.18], p = 0.007). CONCLUSIONS: The presence of antinuclear antibodies in
      healthy individuals at low levels may not mean an autoimmune condition; however,
      it could reflect exposure to environmental factors that have not been
      sufficiently studied. New studies of healthy individuals are necessary in order
      to explain the association between the presence of these antibodies and toxic and
      environmental factors and their effects on health.

PMID- 25393861
TI  - [Costs of appendicitis treatment by diagnosis-related groups in a third-level
      pediatric hospital].
AB  - BACKGROUND: Diagnosis-related groups (DRGs) are widely used in Europe. They allow
      performing comparisons in hospitals and incurrent hospital payment systems,
      defining the payment categories. We undertook this study to classify children who
      underwent appendectomy according to DRGs. METHODS: Cross-sectional study.
      Comorbidities, length of hospitalization, histopathologic classification, and DRG
      classifications were analyzed. RESULTS: We included 313 patients, 62% males, with
      an average age of 8 +/- 3 years; 91% were referred by another hospital and 67%
      were treated at night. Average length of hospitalization was 4 +/- 3 days. There
      were comorbidities in 8% and surgical complications in 11%. According to
      histopathology, appendicitis was edematous (11%), suppurative (36%), gangrenous
      (22%), perforated (29%), and abscessed (2%). At discharge, 97% of the patients
      were healthy. Total cost for DRG 343 was $10,470,173.00 (Mexican pesos), DRG 342
      was $1,227,592.00 and DRG 340 was $511,521.00. The global amount was
      $12,209,286.00 (Mexican pesos). CONCLUSION: The unitary cost for treatment of
      appendectomy for DRG 343 was $37,935.00, for DRG 342 was $49,103.00 and for DRG
      340 was $42,626.00 (Mexican pesos). Because 88% of the cases of appendicitis were
      uncomplicated, this amount of money could be spent to treat these patients in a
      second-level hospital, using reimbursement 343 without generating additional
      expenses.

PMID- 25393862
TI  - [The role of contrast-enhanced computed tomography scan in clinical decision in
      the management of adhesive small bowel obstruction].
AB  - BACKGROUND: Computed tomography (CT) is currently the exam of choice for bowel
      obstruction. The test reports the etiology, site and grade of obstruction, and
      the presence of bowel ischemia, affecting the surgical decision. We undertook
      this study to determine the diagnostic accuracy of CT for bowel ischemia and the
      probability of surgery depending on signs of bowel ischemia and grade of bowel
      obstruction observed in CT in patients with adhesive small bowel obstruction.
      METHODS: We carried out a retrospective study including patients from 2007-2010
      admitted due to adhesive bowel obstruction and with intravenous contrast-enhanced
      abdominopelvic CT at admission. Tomographic signs of bowel ischemia were
      established and diagnostic accuracy was calculated. We also determined the
      probability of surgery depending on tomographic grade of obstruction and signs of
      bowel ischemia by subgroup analysis. RESULTS: This was a cohort of 164 patients
      with a mean age of 60.4 +/- 20 years; 87% had previous abdominal surgery and 86
      patients required surgery (52%). In regard to tomographic signs of bowel
      ischemia, sensitivity was 72.5%, specificity 97.5%, positive predictive value
      90%, negative predictive value 91%, positive likelihood ratio 29.9, and negative
      likelihood ratio 0.28. Tomographic signs of bowel ischemia simultaneously with
      high-grade obstruction presented an 83% probability of surgery; high-grade
      obstruction alone presented a 57% probability and in absence of both signs was
      36%. CONCLUSIONS: There is good diagnostic accuracy for tomographic signs of
      bowel ischemia and its definitive presence. Tomographic signs of bowel ischemia
      simultaneously with high-grade bowel obstruction significantly increase the
      probability of surgery.

PMID- 25393863
TI  - [Transplant coordinator: organ donation process].
AB  - BACKGROUND: Spain is a leader in organ donations although it seems that this
      number does not increase in the same proportion that the waiting list and it is
      necessary to decrease the refusal situations, which are ~16%. METHOD: Analytic
      study. We review the reports prepared by the coordinators of transplants archived
      at the hospital La Fe during the period between May 1, 2004 and December 31,
      2007, resulting in conceptualization and categorization. RESULTS: Sixty-nine
      topics were obtained from the point of view of the family and 11 from the point
      of view of the interviewer. After its conceptualization, codification and
      classification, we proceeded to create an appropriate text. CONCLUSIONS: Certain
      guidelines may be offered that allow us to standardize the action of transplant
      coordinators during the interview and to be more effective.

PMID- 25393864
TI  - [Zenker's diverticulum: election of surgical treatment and outcome. Case
      presentation].
AB  - BACKGROUND: Zenker's diverticulum is a protrusion of the pharyngeal mucosa
      through a weak area of the posterior wall. It is a rare disorder with an
      incidence in Mexico of ~0.04% of the population. Its pathophysiology is not yet
      completely understood. Treatment is surgical and is performed in case of
      complications. Clinic case: We present the case of a 67 year-old male patient
      without comorbidities. Symptoms appeared 15 months prior to admission with
      occasional dysphagia to solids and liquids, breathing difficulty at night,
      drooling, halitosis, 3 kg weight loss in 2 months, and adequate appetite.
      Diagnosis of Zenker's diverticulum was established by imaging method and
      endoscopy. A diverticulectomy with cricopharyngeal muscle myotomy was
      successfully performed. Liquid diet was started the third postoperative day and
      progressed without complications; the patient was discharged on the sixth
      postoperative day without complications. Follow-up at 1 year was successful
      without recurrence. CONCLUSION: Minimally invasive procedures are useful in
      patients with comorbidities and for the short anesthesia time and
      hospitalization. Referring to our field of work, the open treatment is best to
      relieve symptoms rather than endoscopic procedures because the training for
      advanced endoscopic procedures is a problem due to lack of infrastructure and
      specialized personnel.

PMID- 25393865
TI  - [Type IV paraesophageal hernia with 60% of gastric necrosis. Case report].
AB  - BACKGROUND: Paraesophageal hernias are rare and, when associated with symptoms,
      the risk of complications increases, becoming a surgical emergency. CLINICAL
      CASE: We report a case of a 53 year-old female with 3 weeks of clinical evolution
      including abdominal pain, nausea and occasional vomiting; 24 h prior to admission
      she presented intestinal occlusion. Radiographic and tomographic findings showed
      a paraesophageal hernia, requiring exploratory laparotomy, which demonstrated a 9
      cm paraesophageal diaphragmatic defect with a hernia sac containing transverse
      colon, omentum, fundus and body of the stomach (this last one presented ~60% of
      necrosis), performing nonanatomic gastrectomy and simple diaphragmatic
      reconstruction. The patient had a complicated postoperative period requiring two
      additional surgeries attempting to correct gastrectomy dehiscence and ending with
      a third procedure for cervical esophagostomy and Witzel jejunostomy. CONCLUSIONS:
      Elective repair is recommended in all patients with asymptomatic paraesophageal
      hernia in order to avoid possible complications. The approach method is dependent
      on the surgeon's experience and the conditions of the hernia and involved
      structures at the time of diagnosis.

PMID- 25393866
TI  - [Esophagectomy with immediate reconstruction in esophageal trauma. Case report].
AB  - BACKGROUND: Noniatrogenic traumatic injuries of the esophagus are rare and are
      associated with considerable morbidity and mortality. This result is influenced
      by the time elapsed, severity of injury and concomitant organ damage. Current
      management is controversial. Different treatment options exist; however, choice
      should be individualized to obtain the best result. OBJECTIVE: To discuss the
      current management of esophageal trauma. CLINICAL CASE: We report the case of a
      19 year-old male with a grade V esophageal injury caused by shotgun and treated
      by esophagectomy and immediate gastric reconstruction. CONCLUSION: Current
      treatment of traumatic iatrogenic esophageal injury should be individualized for
      a better clinical outcome.

PMID- 25393867
TI  - [Hepatic artery pseudoaneurysm: report of two cases].
AB  - BACKGROUND: Hepatic pseudoaneurysm is rare and potentially fatal. It occurs as a
      consequence of injury to the vascular wall, erosion diathermy through clips,
      biliary leakage and secondary infection. The main symptom is intra-abdominal
      bleeding. OBJECTIVE: To communicate the case of two patients with hepatic
      pseudoaneurysm. CLINICAL CASES: Case 1: We present a 43 year-old male with a
      history of grade IV liver injury due to blunt abdominal trauma and managed
      surgically. Case 2: A 67 year-old man with bile duct injury after laparoscopic
      cholecystectomy. Both patients presented with biliary leakage, abdominal sepsis
      and late intra-abdominal bleeding. Tomographic studies showed the lesion.
      Superselective embolization was performed proximal and distal to the lesion with
      good results. During follow-up, none of them showed signs of recurrent bleeding.
      CONCLUSIONS: Hepatic artery pseudoaneurysm is rare and usually secondary to bile
      duct injury associated with vascular injury after cholecystectomy or liver
      trauma. Arteriography with embolization is the best diagnostic and therapeutic
      procedure. Surgery is indicated for hemodynamically unstable patients,
      embolization failure or rebleeding. Early diagnosis reduces morbidity and
      mortality of this complication.

PMID- 25393868
TI  - [Therapeutic options for portal hypertensive biliopathy: case series and
      literature review].
AB  - BACKGROUND: Portal hypertensive biliopathy is an underdiagnosed condition because
      only some patients have symptoms. The major clinical manifestations include
      cholestasis and cholangitis. The aim of this study is to present a series of
      cases evaluated, treated and followed at a tertiary-care public institution.
      CLINICAL CASE: Four patients with portal hypertensive biliopathy were exposed to
      different therapeutic approaches focused on the management of portal hypertension
      and biliary decompression. They were followed for ~5 years. Three cases achieved
      a favorable outcome with symptom remission, but one patient died while attempting
      dilatation of the bile duct. Finally, we carried out a literature review about
      actual portal hypertensive biliopathy therapeutics. CONCLUSIONS: There is
      currently no consensus on the optimal treatment for this condition. The goal is
      to decompress the biliary tree. Each case should be individually evaluated to
      choose the best treatment option.

PMID- 25393869
TI  - [Severe lower gastrointestinal bleeding due to GIST tumor. Radiological
      embolization and surgery].
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST) were identified only recently.
      These tumors usually have no symptoms, although they are localized, operable and
      curable. Although rare, if they are not diagnosed and treated early, they become
      very aggressive. The most common manifestation is gastrointestinal bleeding from
      mucosal erosion. Their presentation as severe lower gastrointestinal bleeding is
      exceptional. CLINICAL CASE: We report a patient with severe lower
      gastrointestinal bleeding stabilized by interventional radiology that
      subsequently required surgery for definitive care. CONCLUSIONS: Therapeutic use
      of radiological embolization is increasingly widespread in bleeding at various
      levels, achieving hemodynamic stabilization of patients. However, it must be kept
      in mind that, in cases of unknown etiology of lower gastrointestinal bleeding,
      possible causes must be investigated.

PMID- 25393870
TI  - [Surgical Medical Meetings in the Mexican Social Security Institute: 17 years of
      existence].
AB  - The Surgical Medical Meetings Program aims to make highly specialized medical
      services to the marginalized rural population. Surgical Medical Encounters
      highlight the experience and results of an innovative strategy characterized by
      continuous improvement and the desire to continue transcending health for the
      most vulnerable populations. During 17 years of its inception, it is interesting
      to describe the evolution and achievements of the program. 

PMID- 25393871
TI  - [Twenty years of bioethics in Mexico: development and perspectives of the
      National Bioethics Commission].
AB  - Bioethics in Mexico has a history that reveals the vision and ethical commitment
      of iconic characters in the fields of health sciences and humanities, leading to
      the creation of the National Bioethics Commission responsible for promoting a
      bioethics culture in Mexico. Its development and consolidation from the higher
      perspective of humanism had the aim to preserve health, life and its environment,
      while at the same time the bases of ethics and professional practice from
      different perspectives have been the building blocks of medical practice. 

PMID- 25393873
TI  - A voxel-based investigation for MRI-only radiotherapy of the brain using ultra
      short echo times.
AB  - Radiotherapy (RT) based on magnetic resonance imaging (MRI) as the only modality,
      so-called MRI-only RT, would remove the systematic registration error between MR
      and computed tomography (CT), and provide co-registered MRI for assessment of
      treatment response and adaptive RT. Electron densities, however, need to be
      assigned to the MRI images for dose calculation and patient setup based on
      digitally reconstructed radiographs (DRRs). Here, we investigate the geometric
      and dosimetric performance for a number of popular voxel-based methods to
      generate a so-called pseudo CT (pCT). Five patients receiving cranial
      irradiation, each containing a co-registered MRI and CT scan, were included. An
      ultra short echo time MRI sequence for bone visualization was used. Six methods
      were investigated for three popular types of voxel-based approaches; (1)
      threshold-based segmentation, (2) Bayesian segmentation and (3) statistical
      regression. Each approach contained two methods. Approach 1 used bulk density
      assignment of MRI voxels into air, soft tissue and bone based on logical masks
      and the transverse relaxation time T2 of the bone. Approach 2 used similar bulk
      density assignments with Bayesian statistics including or excluding additional
      spatial information. Approach 3 used a statistical regression correlating MRI
      voxels with their corresponding CT voxels. A similar photon and proton treatment
      plan was generated for a target positioned between the nasal cavity and the
      brainstem for all patients. The CT agreement with the pCT of each method was
      quantified and compared with the other methods geometrically and dosimetrically
      using both a number of reported metrics and introducing some novel metrics. The
      best geometrical agreement with CT was obtained with the statistical regression
      methods which performed significantly better than the threshold and Bayesian
      segmentation methods (excluding spatial information). All methods agreed
      significantly better with CT than a reference water MRI comparison. The mean
      dosimetric deviation for photons and protons compared to the CT was about 2% and
      highest in the gradient dose region of the brainstem. Both the threshold based
      method and the statistical regression methods showed the highest dosimetrical
      agreement.Generation of pCTs using statistical regression seems to be the most
      promising candidate for MRI-only RT of the brain. Further, the total amount of
      different tissues needs to be taken into account for dosimetric considerations
      regardless of their correct geometrical position.

PMID- 25393872
TI  - Hidden disease susceptibility and sexual dimorphism in the heterozygous knockout
      of Cyp51 from cholesterol synthesis.
AB  - We examined the genotype-phenotype interactions of Cyp51+/- mice carrying one
      functional allele of lanosterol 14alpha-demethylase from cholesterol
      biosynthesis. No distinct developmental or morphological abnormalities were
      observed by routine visual inspection of Cyp51+/- and Cyp51+/+ mice and fertility
      was similar. We further collected a large data-set from female and male Cyp51+/-
      mice and controls fed for 16 weeks with three diets and applied linear regression
      modeling. We used 3 predictor variables (genotype, sex, diet), and 39 response
      variables corresponding to the organ characteristics (7), plasma parameters (7),
      and hepatic gene expression (25). We observed significant differences between
      Cyp51+/- and wild-type mice in organ characteristics and blood lipid profile.
      Hepatomegaly was observed in Cyp51+/- males, together with elevated total and low
      density lipoprotein cholesterol. Cyp51+/- females fed high-fat, high-cholesterol
      diet were leaner and had elevated plasma corticosterone compared to controls. We
      observed elevated hepatocyte apoptosis, mitosis and lipid infiltration in
      heterozygous knockouts of both sexes. The Cyp51+/- females had a modified lipid
      storage homeostasis protecting them from weight-gain when fed high-fat high
      cholesterol diet. Malfunction of one Cyp51 allele therefore initiates disease
      pathways towards cholesterol-linked liver pathologies and sex-dependent response
      to dietary challenge. 

PMID- 25393875
TI  - Insights into the electronic structure of Cu(II) bound to an imidazole analogue
      of westiellamide.
AB  - Three synthetic analogues of westiallamide, H3L(wa), have previously been
      synthesized (H3L(1-3)) that have a common backbone (derived from l-valine) with
      H3L(wa) but differ in their heterocyclic rings (imidazole, oxazole, thiazole, and
      oxazoline). Herein we explore in detail through high-resolution pulsed electron
      paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy
      in conjunction with density functional theory (DFT) the geometric and electronic
      structures of the mono- and dinuclear Cu(II) complexes of these cyclic pseudo
      hexapeptides. Orientation-selective hyperfine sublevel correlation, electron
      nuclear double resonance, and three-pulse electron spin echo envelope modulation
      spectroscopy of [Cu(II)(H2L(1))(MeOH)2](+) reveal delocalization of the unpaired
      electron spin onto the ligating and distal nitrogens of the coordinated
      heterocyclic rings and that they are magnetically inequivalent. DFT calculations
      confirm this and show similar spin densities on the distal heteroatoms in the
      heterocyclic rings coordinated to the Cu(II) ion in the other cyclic pseudo
      hexapeptide [Cu(II)(H2L(2,3,wa))(MeOH)2](+) complexes. The magnetic
      inequivalencies in [Cu(II)(H2L(1))(MeOH)2](+) arise from different orientations
      of the heterocyclic rings coordinated to the Cu(II) ion, and the delocalization
      of the unpaired electron onto the distal heteroatoms within these N
      methylimidazole rings depends upon their location with respect to the Cu(II)
      d(x(2)-y(2)) orbital. A systematic study of DFT functionals and basis sets was
      undertaken to examine the ability to reproduce the experimentally determined spin
      Hamiltonian parameters. Inclusion of spin-orbit coupling (SOC) using MAG-ReSpect
      or ORCA with a BHLYP/IGLO-II Wachters setup with SOC corrections and ~38% Hartree
      Fock exchange gave the best predictions of the g and A((63)Cu) matrices. DFT
      calculations of the (14)N hyperfine and quadrupole parameters for the distal
      nitrogens of the coordinated heterocyclic rings in [Cu(II)(H2L(1))(MeOH)2](+)
      with the B1LYP functional and the SVP basis set were in excellent agreement with
      the experimental data, though other choices of functional and basis set also
      provided reasonable values. MCD, EPR, mass spectrometry, and DFT showed that
      preparation of the dinuclear Cu(II) complex in a 1:1 MeOH/glycerol mixture
      (necessary for MCD) resulted in the exchange of the bridging methoxide ligand for
      glycerol with a corresponding decrease in the magnitude of the exchange coupling.

PMID- 25393874
TI  - A statistical method of identifying interactions in neuron-glia systems based on
      functional multicell Ca2+ imaging.
AB  - Crosstalk between neurons and glia may constitute a significant part of
      information processing in the brain. We present a novel method of statistically
      identifying interactions in a neuron-glia network. We attempted to identify
      neuron-glia interactions from neuronal and glial activities via maximum-a
      posteriori (MAP)-based parameter estimation by developing a generalized linear
      model (GLM) of a neuron-glia network. The interactions in our interest included
      functional connectivity and response functions. We evaluated the cross-validated
      likelihood of GLMs that resulted from the addition or removal of connections to
      confirm the existence of specific neuron-to-glia or glia-to-neuron connections.
      We only accepted addition or removal when the modification improved the cross
      validated likelihood. We applied the method to a high-throughput, multicellular
      in vitro Ca2+ imaging dataset obtained from the CA3 region of a rat hippocampus,
      and then evaluated the reliability of connectivity estimates using a statistical
      test based on a surrogate method. Our findings based on the estimated
      connectivity were in good agreement with currently available physiological
      knowledge, suggesting our method can elucidate undiscovered functions of neuron
      glia systems. 

PMID- 25393876
TI  - Identification of allelic heterogeneity at type-2 diabetes loci and impact on
      prediction.
AB  - Although over 60 single nucleotide polymorphisms (SNPs) have been identified by
      meta-analysis of genome-wide association studies for type-2 diabetes (T2D) among
      individuals of European descent, much of the genetic variation remains
      unexplained. There are likely many more SNPs that contribute to variation in T2D
      risk, some of which may lie in the regions surrounding established SNPs--a
      phenomenon often referred to as allelic heterogeneity. Here, we use the summary
      statistics from the DIAGRAM consortium meta-analysis of T2D genome-wide
      association studies along with linkage disequilibrium patterns inferred from a
      large reference sample to identify novel SNPs associated with T2D surrounding
      each of the previously established risk loci. We then examine the extent to which
      the use of these additional SNPs improves prediction of T2D risk in an
      independent validation dataset. Our results suggest that multiple SNPs at each of
      3 loci contribute to T2D susceptibility (TCF7L2, CDKN2A/B, and KCNQ1; p<5*10(
      8)). Using a less stringent threshold (p<5*10(-4)), we identify 34 additional
      loci with multiple associated SNPs. The addition of these SNPs slightly improves
      T2D prediction compared to the use of only the respective lead SNPs, when
      assessed using an independent validation cohort. Our findings suggest that some
      currently established T2D risk loci likely harbor multiple polymorphisms which
      contribute independently and collectively to T2D risk. This opens a promising
      avenue for improving prediction of T2D, and for a better understanding of the
      genetic architecture of T2D.

PMID- 25393877
TI  - Prospective randomized trial of enoxaparin, pentoxifylline and ursodeoxycholic
      acid for prevention of radiation-induced liver toxicity.
AB  - BACKGROUND/AIM: Targeted radiotherapy of liver malignancies has found to be
      effective in selected patients. A key limiting factor of these therapies is the
      relatively low tolerance of the liver parenchyma to radiation. We sought to
      assess the preventive effects of a combined regimen of pentoxifylline (PTX),
      ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on
      focal radiation-induced liver injury (fRILI). METHODS AND MATERIALS: Patients
      with liver metastases from colorectal carcinoma who were scheduled for local
      ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy)
      were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks
      (treatment) or no medication (control). Focal RILI at follow-up was assessed
      using functional hepatobiliary magnetic resonance imaging (MRI). A minimal
      threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly
      exposed to, was quantified by merging MRI and dosimetry data. RESULTS: Results
      from an intended interim-analysis made a premature termination necessary. Twenty
      two patients were included in the per-protocol analysis. Minimal mean hepatic
      threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly
      higher in the study treatment-group compared with the control (19.1 Gy versus
      14.6 Gy, p = 0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed
      in 45.5% of patients in the treatment versus 90.9% of the control group. No
      significant differences between the groups were observed at the 12-week follow
      up. CONCLUSIONS: The post-therapeutic application of PTX, UDCA and low-dose LMWH
      significantly reduced the extent and incidence fRILI at 6 weeks after
      radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after
      cessation of PTX, UDCA and LMWH during weeks 1-8) in the treatment group was
      comparable to the control group thus supporting the observation that the agents
      mitigated fRILI. TRIAL REGISTRATION: EU clinical trials register 2008-002985-70
      ClinicalTrials.gov NCT01149304.

PMID- 25393879
TI  - Ambient stable zwitterionic perylene bisimide-centered radical.
AB  - The unexpected introduction of a cationic imidazolium substituent in the 2
      position of a tetrachloro-substituted perylene-3,4:9,10-tetracarboxylic acid
      bisimide (PBI) by the reaction of PBI-Cl4 1 with the N-heterocyclic carbene 1,3
      di-iso-propyl-imidazolin-2-ylidene ((i)Pr2Im 2) enables the isolation of an
      ambient stable zwitterionic radical. The remarkable stability of this
      unprecedented PBI-centered radical facilitates the complete characterization by
      several spectroscopic methods as well as single crystal structure analysis. Redox
      studies revealed that (i)Pr2Im-PBI-Cl4 4 can be transferred reversibly to the
      corresponding anion and cation, respectively, even on a preparative scale.

PMID- 25393878
TI  - NIAM-deficient mice are predisposed to the development of proliferative lesions
      including B-cell lymphomas.
AB  - Nuclear Interactor of ARF and Mdm2 (NIAM, gene designation Tbrg1) is a largely
      unstudied inhibitor of cell proliferation that helps maintain chromosomal
      stability. It is a novel activator of the ARF-Mdm2-Tip60-p53 tumor suppressor
      pathway as well as other undefined pathways important for genome maintenance. To
      examine its predicted role as a tumor suppressor, we generated NIAM mutant
      (NIAM(m/m)) mice homozygous for a beta-galactosidase expressing gene-trap
      cassette in the endogenous gene. The mutant mice expressed significantly lower
      levels of NIAM protein in tissues compared to wild-type animals. Fifty percent of
      aged NIAM deficient mice (14 to 21 months) developed proliferative lesions,
      including a uterine hemangioma, pulmonary papillary adenoma, and a Harderian
      gland adenoma. No age-matched wild-type or NIAM(+/m) heterozygous animals
      developed lesions. In the spleen, NIAM(m/m) mice had prominent white pulp
      expansion which correlated with enhanced increased reactive lymphoid hyperplasia
      and evidence of systemic inflammation. Notably, 17% of NIAM mutant mice had
      splenic white pulp features indicating early B-cell lymphoma. This correlated
      with selective expansion of marginal zone B cells in the spleens of younger,
      tumor-free NIAM-deficient mice. Unexpectedly, basal p53 expression and activity
      was largely unaffected by NIAM loss in isolated splenic B cells. In sum, NIAM
      down-regulation in vivo results in a significant predisposition to developing
      benign tumors or early stage cancers. These mice represent an outstanding
      platform for dissecting NIAM's role in tumorigenesis and various anti-cancer
      pathways, including p53 signaling.

PMID- 25393880
TI  - A family-based joint test for mean and variance heterogeneity for quantitative
      traits.
AB  - Traditional quantitative trait locus (QTL) analysis focuses on identifying loci
      associated with mean heterogeneity. Recent research has discovered loci
      associated with phenotype variance heterogeneity (vQTL), which is important in
      studying genetic association with complex traits, especially for identifying gene
      gene and gene-environment interactions. While several tests have been proposed to
      detect vQTL for unrelated individuals, there are no tests for related
      individuals, commonly seen in family-based genetic studies. Here we introduce a
      likelihood ratio test (LRT) for identifying mean and variance heterogeneity
      simultaneously or for either effect alone, adjusting for covariates and family
      relatedness using a linear mixed effect model approach. The LRT test statistic
      for normally distributed quantitative traits approximately follows chi(2)
      distributions. To correct for inflated Type I error for non-normally distributed
      quantitative traits, we propose a parametric bootstrap-based LRT that removes the
      best linear unbiased prediction (BLUP) of family random effect. Simulation
      studies show that our family-based test controls Type I error and has good power,
      while Type I error inflation is observed when family relatedness is ignored. We
      demonstrate the utility and efficiency gains of the proposed method using data
      from the Framingham Heart Study to detect loci associated with body mass index
      (BMI) variability.

PMID- 25393881
TI  - The melatonin-N,N-dibenzyl(N-methyl)amine hybrid ITH91/IQM157 affords
      neuroprotection in an in vitro Alzheimer's model via hemo-oxygenase-1 induction.
AB  - We have investigated the protective effects of ITH91/IQM157, a hybrid of
      melatonin and N,N-dibenzyl(N-methyl)amine, in an in vitro model of Alzheimer's
      disease (AD)-like pathology that combines amyloid beta (Abeta) and tau
      hyperphosphorylation induced by okadaic acid (OA), in the human neuroblastoma
      cell line SH-SY5Y. Combination of subtoxic concentrations of Abeta and OA caused
      a significant toxicity of 40% cell death, which mainly was apoptotic; this effect
      was accompanied by retraction of the cells' prolongations and accumulation of
      thioflavin-S stained protein aggregates. In this toxicity model, ITH91/IQM157 (1
      1000 nM) reduced cell death measured as MTT reduction; at 100 nM, it prevented
      apoptosis, retraction of prolongations, and Abeta aggregates. The protective
      actions of ITH91/IQM157 were blocked by mecamylamine, luzindol, chelerythrine,
      PD98059, LY294002, and SnPP. We show that the combination of melatonin with a
      fragment endowed with AChE inhibition in a unique chemical structure,
      ITH91/IQM157, can reduce neuronal cell death induced by Abeta and OA by a
      signaling pathway that implicates both nicotinic and melatonin receptors, PKC,
      Akt, ERK1/2, and induction of hemoxygenase-1. 

PMID- 25393882
TI  - Fitness to fly in patients with lung disease.
AB  - Patients with chronic lung disease may have mild hypoxemia at sea level. Some of
      these cases may go unrecognized, and even among those who are known to be
      hypoxemic, some do not use supplemental oxygen. During air travel in a hypobaric
      hypoxic environment, compensatory pulmonary mechanisms may be inadequate in
      patients with lung disease despite normal sea-level oxygen requirements. In
      addition, compensatory cardiovascular mechanisms may be less effective in some
      patients who are unable to increase cardiac output. Air travel also presents an
      increased risk of venous thromboembolism. Patients with cystic lung disease may
      also be at increased risk of pneumothorax. Although overall this risk appears to
      be relatively low, should a pneumothorax occur, it could present a significant
      challenge to the patient with chronic lung disease, particularly if hypoxemia is
      already present. As such, a thorough assessment of patients with chronic lung
      disease and cardiac disease who are contemplating air travel should be performed.
      The duration of the planned flight, the anticipated levels of activity, comorbid
      illnesses, and the presence of risk factors for venous thromboembolism are
      important considerations. Hypobaric hypoxic challenge testing reproduces an
      environment most similar to that encountered during actual air travel; however,
      it is not widely available. Assessment for hypoxia is otherwise best performed
      using a normobaric hypoxic challenge test. Patients in need of supplemental
      oxygen need to contact the airline and request this accommodation during flight.
      They should also be advised on arranging portable oxygen concentrators before air
      travel, and a discussion of the potential risks of travel should take place.

PMID- 25393883
TI  - Simulation-based education for transfusion medicine.
AB  - BACKGROUND: The administration of blood products is frequently determined by
      physicians without subspecialty training in transfusion medicine (TM). Education
      in TM is necessary for appropriate utilization of resources and maintaining
      patient safety. Our institution developed an efficient simulation-based TM course
      with the goal of identifying key topics that could be individualized to learners
      of all levels in various environments while also allowing for practice in an
      environment where the patient is not placed at risk. STUDY DESIGN AND METHODS: A
      2.5-hour simulation-based educational activity was designed and taught to
      undergraduate medical students rotating through anesthesiology and TM elective
      rotations and to all Clinical Anesthesia Year 1 (CA-1) residents. Content and
      process evaluation of the activity consisted of multiple-choice tests and course
      evaluations. RESULTS: Seventy medical students and seven CA-1 residents were
      enrolled in the course. There was no significant difference on pretest results
      between medical students and CA-1 residents. The posttest results for both
      medical students and CA-1 residents were significantly higher than pretest
      results. The results of the posttest between medical students and CA-1 residents
      were not significantly different. CONCLUSION: The TM knowledge gap is not a
      trivial problem as transfusion of blood products is associated with significant
      risks. Innovative educational techniques are needed to address the ongoing
      challenges with knowledge acquisition and retention in already full curricula.
      Our institution developed a feasible and effective way to integrate TM into the
      curriculum. Educational activities, such as this, might be a way to improve the
      safety of transfusions.

PMID- 25393884
TI  - Ribavirin shows immunomodulatory effects on activated microglia.
AB  - Abstract Ribavirin (RBV) is synthetic purine nucleoside analogue, licensed as
      anti-viral drug that displays immunomodulatory actions on various immune cells.
      Our previous ex vivo studies have demonstrated immunosuppressive effects of RBV
      on reactive T-lymphocytes in experimental autoimmune encephalomyelitis. Here, we
      examined the effects of RBV on inflammatory response of microglia. RBV potency to
      down-regulate microglia inflammatory response was assessed by measuring microglia
      cell body size, and the production of nitric oxide (NO) and pro- and anti
      inflammatory cytokines. RBV exerted cytotoxic effects on LPS-stimulated
      microglia, leaving non-stimulated microglia unaffected. The exposure of activated
      microglia to RBV led to: decrease in the level of NO as a result of decreased
      cell number, lower average cell surface, the reduction of membrane ruffling, the
      suppression of interleukin-6 release and promoted interleukin-10 production. On
      the other hand, RBV promoted LPS-induced interleukin-1 beta release. Our results
      imply that RBV is a complex immunomodulator showing both anti- and pro
      inflammatory effects on activated microglia. 

PMID- 25393885
TI  - Hydrogen bonding induced enhancement of Fermi resonances: ultrafast vibrational
      energy flow dynamics in aniline-d5.
AB  - With hydrogen bonding of the amino group of aniline-d5 we can identify the roles
      of Fermi enhanced combination and overtone states in intramolecular vibrational
      re-distribution (IVR) pathways for N-H stretching excitations. Using linear
      Fourier transform infrared (FT-IR) spectroscopy, ultrafast one- and two-color IR
      pump-IR-probe spectroscopy, and femtosecond two-dimensional IR spectroscopy, we
      can identify the primary accepting modes for N-H stretching excitations. In
      particular, a key role is played by the delta(NH2) bending degree of freedom,
      either via its delta = 2 overtone state or via a combination state with the
      nu(C?C) ring stretching mode. No significant transient population in these Fermi
      enhanced combination/overtone states can be observed, a consequence of similar
      decay rates of these Fermi enhanced combination/overtone states and of the N-H
      stretching states. A similar magnitude of the transient response of the two
      fingerprint modes regardless of direct excitation of the Fermi enhanced
      combination/overtone levels or of the N-H stretching states suggests an
      underlying coupling mechanism facilitating common IVR pathways. This mechanism is
      expected to be of general importance for other organic compounds with hydrogen
      bonded amino groups, including DNA bases. 

PMID- 25393886
TI  - A propensity score-matched case-control comparative study of laparoscopic and
      open liver resection for hepatocellular carcinoma.
AB  - BACKGROUND: The aim of this study was to compare the perioperative and long-term
      oncologic outcomes of laparoscopic liver resection (LLR) and open liver resection
      (OLR) for single hepatocellular carcinoma (HCC) in case-controlled patient groups
      using the propensity score. PATIENTS AND METHODS: Between January 2005 and
      February 2013, 292 patients underwent surgical resection for HCC. Of these, 202
      patients who underwent surgical resection for initial treatment for a single mass
      were enrolled. These patients were divided into two groups according to the
      method of operation: the Lap group (patients who underwent LLR) and the Open
      group (patients who underwent OLR). To correct different demographic and clinical
      factors in the two groups, propensity score matching was used at a 1:1 ratio,
      and, finally, 102 patients were enrolled in this study, 51 patients in each
      group. Preoperative characteristics, perioperative results, and long-term results
      were retrospectively analyzed based on the prospectively recorded database.
      RESULTS: Preoperative baseline variables were well balanced in both groups. There
      were no differences of extent of surgery and rate of anatomical resection between
      the two groups. With the exception of a shorter postoperative hospital stay in
      the Lap group than that of the Open group (8.2 days versus 12.3 days; P=.004),
      there were no significant differences in perioperative, pathological, and long
      term outcomes. The 5-year overall survival rates were 80.1% in the Lap group and
      85.7% in the Open group, respectively (P=.173). The 5-year disease-free survival
      rates were 67.8% in the Lap group and 54.8% in the Open group, respectively
      (P=.519). CONCLUSIONS: LLR for HCC is safe, and long-term oncologic outcomes in
      selected patients were comparable to those who underwent OLR.

PMID- 25393887
TI  - Stable but reactive perfluoroalkylzinc reagents: application in ligand-free
      copper-catalyzed perfluoroalkylation of aryl iodides.
AB  - The aromatic perfluoroalkylation catalyzed by a copper(I) salt with
      bis(perfluoroalkyl)zinc reagents Zn(RF)2(DMPU)2, which were prepared and then
      isolated as a stable white powder from perfluoroalkyl iodide and diethylzinc, was
      accomplished to provide the perfluoroalkylated products in good-to-excellent
      yields. The advantages of this reliable and practical catalytic reaction are 1)
      air-stable and easy-to-handle bis(perfluoroalkyl)zinc reagents can be utilized,
      2) the reagent is reactive and hence the operation without activators and ligands
      is simple, and 3) not only trifluoromethylation but also perfluoroalkylation can
      be attained.

PMID- 25393888
TI  - A pioneer of Australian paediatrics: Dr Henry Edward Brown (1858-1931).
AB  - The emergence of paediatrics as a specialty in Australian medicine dates from the
      last two decades of the 19th century. Among the pioneers of pre-Federation
      paediatrics, we include Dr Henry Edward Brown (1858-1931), an Irish-born
      physician and surgeon who became the first paediatrician to practise in the
      northern half of the Australian continent. In 1885, he was appointed as the
      medical superintendent of the Rockhampton Children's Hospital, itself a pioneer
      institution in the care of sick and injured children. Dr H.E. Brown also served
      as medical officer of health concurrently in three Queensland shires. He was a
      leader in the literary and sporting life of the busy port town of Rockhampton and
      a scholar and significant philanthropist in the domain of French literature. His
      life was and remains an exemplar of a class of pre-Federation paediatricians who
      established the ethos of clinical and societal service, which remains as a core
      feature of the speciality discipline of paediatrics in the 21st century.

PMID- 25393889
TI  - Are antidepressants equally effective in the long-term treatment of major
      depressive disorder?
AB  - OBJECTIVE: Few studies have compared simultaneously different antidepressants in
      long-term treatment of major depressive disorder (MDD). Long-term prevention of
      recurrences should be the main goal of MDD treatment. The purpose of this study
      was to compare antidepressants of different pharmacological classes in terms of
      retention in treatment (no discontinuation for recurrences, hospitalizations,
      side effects). METHODS: One hundred and fifty outpatients with an MDD diagnosis,
      treated with antidepressants in mono-therapy, were included. Follow-up period was
      set at 24 months, and information have been obtained from charts, interviews with
      patients and their relatives, and from the Lombardy regional register. A survival
      analysis (Kaplan-Meier) was performed, considering recurrences, hospitalizations,
      or discontinuation due to side effects as 'death' events. RESULTS: In our sample,
      48.7% of the patients presented a recurrence within the first 2 years of
      treatment. Bupropion appears less effective in long-term treatment of MDD than
      the other compared antidepressants, with exception of fluoxetine (p = 0.09),
      amitriptyline (p = 0.13), fluvoxamine (p = 0.83), venlafaxine (p = 0.5), and
      trazodone (p = 0.58). Fluvoxamine appears to be less effective than citalopram (p
      = 0.036), paroxetine (p = 0.037), clomipramine (p = 0.05), sertraline (p =
      0.011), and duloxetine (p = 0.024). CONCLUSIONS: Bupropion and fluvoxamine appear
      less effective in long-term treatment of MDD. These results should be confirmed
      by randomized placebo-controlled prospective studies with larger samples.

PMID- 25393890
TI  - Integrated semi-physiological pharmacokinetic model for both sunitinib and its
      active metabolite SU12662.
AB  - AIMS: Previously published pharmacokinetic (PK) models for sunitinib and its
      active metabolite SU12662 were based on a limited dataset or lacked important
      elements such as correlations between sunitinib and its metabolite. The current
      study aimed to develop an improved PK model that circumvented these limitations
      and to prove the utility of the PK model in treatment optimization in clinical
      practice. METHODS: One thousand two hundred and five plasma samples from 70
      cancer patients were collected from three PK studies with sunitinib and SU12662.
      A semi-physiological PK model for sunitinib and SU12662 was developed
      incorporating pre-systemic metabolism using non-linear mixed effects modelling
      (nonmem). Allometric scaling based on body weight was applied. The final model
      was used for simulation of the PK of different treatment regimens. RESULTS:
      Sunitinib and SU12662 PK were best described by a one and two compartment model,
      respectively. Introduction of pre-systemic formation of SU12662 strongly improved
      model fit, compared with solely systemic metabolism. The clearance of sunitinib
      and SU12662 was estimated at 35.7 (relative standard error (RSE) 5.7%) l h(-1)
      and 17.1 (RSE 7.4%) l h(-1), respectively for 70 kg patients. Correlation
      coefficients were estimated between inter-individual variability of both
      clearances, both volumes of distribution and between clearance and volume of
      distribution of SU12662 as 0.53, 0.48 and 0.45, respectively. Simulation of the
      PK model predicted correctly the ratio of patients who did not reach proposed PK
      targets for efficacy. CONCLUSIONS: A semi-physiological PK model for sunitinib
      and SU12662 in cancer patients was presented including pre-systemic metabolism.
      The model was superior to previous PK models in many aspects.

PMID- 25393891
TI  - Enzymatic saccharification of cassava residues and glucose inhibitory kinetics on
      beta-glucosidase from Hypocrea orientalis.
AB  - Cassava residues are byproducts of the starch industry containing abundant
      cellulose for bioproduction of green fuel. To obtain maximum sugar yields from
      cassava residues, the optimal conditions for hydrolyzing the residues were
      determined using cellulase prepared from a novel Hypocrea orientalis strain. The
      optimal pH value and optimal temperature for the cellulase hydrolysis were 5.0
      and 50  degrees C, respectively. The concentration of NaOH was determined to be
      1% for pretreatment of cassava residues to gain enough soluble sugars suitably.
      The yield of released sugars was 10 mg/mL in the optimal conditions after 24 h of
      reaction, which was similar to that of bagasse and wheat grass. Inhibition
      kinetics of H. orientalis beta-glucosidase (BG) by glucose was first studied
      using the progress-of-substrate-reaction method as described by Tsou (Tsou, C. L.
      Adv. Enzymol. Related Areas Mol. Biol. 1988, 61, 381-436), and the microscopic
      inhibition rate constants of glucose were determined. The results showed that
      glucose could inhibit BG reversibly and competitively. The rate constants of
      forward (k(+0)) and reverse (k(-0)) reaction were measured to be 4.88 * 10(-4)
      (mM.s)(-1) and 2.7 * 10(-4) s(-1), respectively. Meanwhile, the inhibition was
      more significant than that of L-glucose, D-mannose, D-galactose, D-aminoglucose,
      acetyl-D-glucose, and D-fructose. This work reveals how to increase sugar yields
      and reduce product inhibition during enzymatic saccharification of cellulose.

PMID- 25393892
TI  - Ethylene-producing bacteria that ripen fruit.
AB  - Ethylene is a plant hormone widely used to ripen fruit. However, the synthesis,
      handling, and storage of ethylene are environmentally harmful and dangerous. We
      engineered E. coli to produce ethylene through the activity of the ethylene
      forming enzyme (EFE) from Pseudomonas syringae. EFE converts a citric acid cycle
      intermediate, 2-oxoglutarate, to ethylene in a single step. The production of
      ethylene was placed under the control of arabinose and blue light responsive
      regulatory systems. The resulting bacteria were capable of accelerating the
      ripening of tomatoes, kiwifruit, and apples. 

PMID- 25393893
TI  - Variation at the 3'-UTR of the goat alphaS2 - and beta-casein genes is not
      associated with milk protein and dry matter contents in Murciano-Granadina goats.

PMID- 25393894
TI  - Posterior capsular opacification and Nd:YAG capsulotomy rates with the iMics Y
      60H and Micro AY intra-ocular lenses: 3-year results of a randomized clinical
      trial.
AB  - PURPOSE: To compare the incidence and intensity of posterior capsular
      opacification (PCO) and neodymium:yttrium-aluminium-garnet (Nd:YAG) capsulotomy
      rates between two microincision intra-ocular lenses (IOLs) 3 years after surgery.
      METHODS: Sixty-five patients randomly received a Y-60H IOL (HOYA Surgical Optics,
      Singapore) in one eye and a Micro AY IOL (PhysIOL, Liege, Belgium) in the
      contralateral eye during same-day bilateral cataract surgery. Eyes were examined
      1 week, 20 months and 3 years after surgery. The amount of PCO (score: 0-10) was
      assessed subjectively at the slit lamp and objectively using automated image
      analysis software (aqua). Additionally, the Nd:YAG capsulotomy rate was noted.
      RESULTS: Three years postoperatively, the objective PCO score of Y-60H IOLs was
      1.9 +/- 1.7 compared to PCO score of 1.7 +/- 2.2 for the Micro AY IOLs (p =
      0.66). Thirty-four percentage of the Y-60H eyes had undergone Nd:YAG capsulotomy,
      compared to 49% of the Micro AY eyes (p = 0.04). Significantly, more capsular
      folds were observed in the Y-60H IOL group (p = 0.001). There was no significant
      difference in best-corrected visual acuity, rhexis/IOL overlap and anterior
      capsule opacification 3 years after surgery. CONCLUSION: Both microincision IOLs
      showed high YAG rates and comparable PCO scores 3 years after surgery. In the
      light of this unsatisfying PCO performance, the advantage of the present
      microincision IOLs over conventional IOLs must be questioned.

PMID- 25393896
TI  - Mosquito-borne viruses and suppressors of invertebrate antiviral RNA silencing.
AB  - The natural maintenance cycles of many mosquito-borne viruses require
      establishment of persistent non-lethal infections in the invertebrate host. While
      the mechanisms by which this occurs are not well understood, antiviral responses
      directed by small RNAs are important in modulating the pathogenesis of viral
      infections in disease vector mosquitoes. In yet another example of an
      evolutionary arms race between host and pathogen, some plant and insect viruses
      have evolved to encode suppressors of RNA silencing (VSRs). Whether or not
      mosquito-borne viral pathogens encode VSRs has been the subject of debate. While
      at first there would seem to be little evolutionary benefit to mosquito-borne
      viruses encoding proteins or sequences that strongly interfere with RNA
      silencing, we present here a model explaining how the expression of VSRs by these
      viruses in the vector might be compatible with the establishment of persistence.
      We also discuss the challenges associated with interrogating these viruses for
      the presence of suppressor proteins or sequences, as well as the candidates that
      have been identified in the genomes of mosquito-borne pathogens thus far.

PMID- 25393895
TI  - The insect microbiome modulates vector competence for arboviruses.
AB  - Diseases caused by arthropod-borne viruses (arboviruses), such as Dengue, West
      Nile, and Chikungunya, constitute a major global health burden and are increasing
      in incidence and geographic range. The natural microbiota of insect vectors
      influences various aspects of host biology, such as nutrition, reproduction,
      metabolism, and immunity, and recent studies have highlighted the ability of
      insect-associated bacteria to reduce vector competence for arboviruses and other
      pathogens. This reduction can occur through mechanisms, such as immune response
      activation, resource competition, or the production of anti-viral molecules.
      Studying the interactions between insect vectors and their microbiota is an
      important step toward developing alternative strategies for arbovirus
      transmission control.

PMID- 25393897
TI  - CMV-promoter driven codon-optimized expression alters the assembly type and
      morphology of a reconstituted HERV-K(HML-2).
AB  - The HERV-K(HML-2) family contains the most recently integrated and best preserved
      endogenized proviral sequences in the human genome. All known elements have
      nevertheless been subjected to mutations or deletions that render expressed
      particles non-infectious. Moreover, these post-insertional mutations hamper the
      analysis of the general biological properties of this ancient virus family. The
      expression of consensus sequences and sequences of elements with reverted post
      insertional mutations has therefore been very instrumental in overcoming this
      limitation. We investigated the particle morphology of a recently reconstituted
      HERV-K113 element termed oriHERV-K113 using thin-section electron microscopy (EM)
      and could demonstrate that strong overexpression by substitution of the 5'LTR for
      a CMV promoter and partial codon optimization altered the virus assembly type and
      morphology. This included a conversion from the regular C-type to an A-type
      morphology with a mass of cytoplasmic immature cores tethered to the cell
      membrane and the membranes of vesicles. Overexpression permitted the release and
      maturation of virions but reduced the envelope content. A weaker boost of virus
      expression by Staufen-1 was not sufficient to induce these morphological
      alterations.

PMID- 25393899
TI  - Role of resistin in the inflammatory response induced by nicotine plus
      lipopolysaccharide in human periodontal ligament cells in vitro.
AB  - BACKGROUND AND OBJECTIVE: Resistin was recently reported to play a role in
      inflammation-related diseases such as arthritis. However, the precise role of
      resistin in chronic inflammatory diseases, such as periodontal disease, remains
      unclear. The aim of this study was to investigate the combined effects of
      nicotine and lipopolysaccharide (LPS) on the expression of resistin and to assess
      whether resistin expression influences the levels of inflammatory cytokines,
      extracellular matrix (ECM) molecules and MMPs in human periodontal ligament cells
      (PDLCs) stimulated with both nicotine and LPS. MATERIAL AND METHODS: PDLCs were
      pretreated with isoproterenol or resistin-specific small interfering RNA (siRNA),
      stimulated with LPS plus nicotine for 24 h, and then monitored for the production
      of inflammatory mediators. The concentrations of prostaglandin E2 (PGE2) and
      nitric oxide (NO) were measured by radioimmunoassay and the Griess method,
      respectively. RT-PCR and western blot analysis were used to measure the levels of
      mRNA and protein, respectively. Western blot analysis was also used to assess the
      activation of various signal-transduction pathways. RESULTS: Treatment with
      nicotine plus LPS up-regulated the expression of resistin mRNA and the production
      of resistin protein in PDLCs in a time- and concentration-dependent manner.
      Isoproterenol-mediated interference with the function of resistin, or siRNA
      mediated knockdown of resistin expression, markedly attenuated the LPS plus
      nicotine-mediated stimulation of PGE2 and NO production, the production of
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase proteins and the
      expression of proinflammatory cytokines [tumor necrosis factor-alpha, interleukin
      (IL)-1beta, IL-6 and IL-12] and MMPs (MMP-1, MMP-2 and MMP-9); however, these
      treatments restored the expression of ECM molecules. Furthermore, pretreatment
      with isoproterenol or resistin-specific siRNA blocked nicotine plus LPS-induced
      activation of phosphoinositide-3-kinase, glycogen synthase kinase-3 beta, beta
      catenin, p38, ERK, JNK and nuclear factor-kappaB. CONCLUSION: This is the first
      study to show that the inhibition of resistin, by either a pharmacological or a
      genetic silencing approach, has anti-inflammatory effects. These effects include
      decreased levels of inflammatory cytokines and the prevention of ECM breakdown in
      a nicotine plus LPS-stimulated PDLC model.

PMID- 25393900
TI  - Analysis of yellowish skin color from an optical image and the development of 3D
      Skin Chroma Diagram(TM).
AB  - BACKGROUND/PURPOSE: This study was conducted to define yellowish skin color,
      which is a major concern of Asian women, and to develop a 3D skin-pigment color
      model. METHODS: A total of 22 Korean females were enrolled in this study. These
      women were asked to use a functional cosmetic product with whitening agents for 8
      weeks. We photographed the subsurface reflection of each subject's face using
      polarized light. The color of the subsurface reflection is a result of diffusive
      light transports that are attenuated by various skin pigments such as melanin,
      hemoglobin, and skin base colors. In this subsurface photo image, we eliminated
      the color effects of melanin and hemoglobin distribution by skin color analysis
      resulting in skin base color. Based on a variety of observed skin base colors
      from which the melanin and hemoglobin pigments have been removed, we defined a
      standard skin color for the entire subject group, and then, we gained a
      particular yellowish skin color by excluding the standard skin color from the
      skin base color again. RESULTS: After applying whitening cosmetic products, the
      amount of melanin and hemoglobin was reduced by 7.3% and 18.6%, respectively.
      Also, through using our new analysis method, yellowish skin color has been
      improved by 2.8%. We showed the improvement on 3D Skin Chroma Diagram(TM) three
      dimensionally. CONCLUSION: It became possible to diagnose yellowish color on
      human skin and to analyze the improvement in skin tone both quantitatively and
      visually.

PMID- 25393898
TI  - Long-distance retinoid signaling in the zebra finch brain.
AB  - All-trans retinoic acid (ATRA), the main active metabolite of vitamin A, is a
      powerful signaling molecule that regulates large-scale morphogenetic processes
      during vertebrate embryonic development, but is also involved post-natally in
      regulating neural plasticity and cognition. In songbirds, it plays an important
      role in the maturation of learned song. The distribution of the ATRA-synthesizing
      enzyme, zRalDH, and of ATRA receptors (RARs) have been described, but information
      on the distribution of other components of the retinoid signaling pathway is
      still lacking. To address this gap, we have determined the expression patterns of
      two obligatory RAR co-receptors, the retinoid X receptors (RXR) alpha and gamma,
      and of the three ATRA-degrading cytochromes CYP26A1, CYP26B1, and CYP26C1. We
      have also studied the distribution of zRalDH protein using immunohistochemistry,
      and generated a refined map of ATRA localization, using a modified reporter cell
      assay to examine entire brain sections. Our results show that (1) ATRA is more
      broadly distributed in the brain than previously predicted by the spatially
      restricted distribution of zRalDH transcripts. This could be due to long-range
      transport of zRalDH enzyme between different nuclei of the song system:
      Experimental lesions of putative zRalDH peptide source regions diminish ATRA
      induced transcription in target regions. (2) Four telencephalic song nuclei
      express different and specific subsets of retinoid-related receptors and could be
      targets of retinoid regulation; in the case of the lateral magnocellular nucleus
      of the anterior nidopallium (lMAN), receptor expression is dynamically regulated
      in a circadian and age-dependent manner. (3) High-order auditory areas exhibit a
      complex distribution of transcripts representing ATRA synthesizing and degrading
      enzymes and could also be a target of retinoid signaling. Together, our survey
      across multiple connected song nuclei and auditory brain regions underscores the
      prominent role of retinoid signaling in modulating the circuitry that underlies
      the acquisition and production of learned vocalizations. 

PMID- 25393901
TI  - Adult-onset recurrent respiratory papillomatosis: a review of disease
      pathogenesis and implications for patient counseling.
AB  - IMPORTANCE: A new diagnosis of adult-onset recurrent respiratory papillomatosis
      (AO-RRP) prompts many questions related to disease acquisition, course, and
      transmission. Recent attention to the human papillomavirus (HPV), along with
      emerging data on AO-RRP, provides a foundation for patient counseling. OBJECTIVE:
      To provide a framework for these discussions, including an overview of the
      current literature on HPV-mediated disease across organs. EVIDENCE REVIEW: The
      peer-reviewed literature was culled to provide a comprehensive review
      encompassing AO-RRP and anogenital papilloma, as well as general HPV virology and
      pathophysiology. PubMed and Google Scholar databases were searched from 1975 to
      July 2014. FINDINGS: Most HPV infections in healthy adults are cleared within 2
      years without clinical significance. Adult-onset RRP is a rare manifestation of
      HPV and may be homologous to anogenital HPV, which is highly transmissible
      between sexual partners. Horizontal transmission of AO-RRP has not been
      characterized. Our laboratory, however, recently found that nearly 100% of
      patients with AO-RRP had concurrent oral cavity HPV infection. Historically, an
      increased number of oral sex partners was thought to be associated with AO-RRP,
      but recent data from our group did not corroborate this finding. Recent data also
      question the dogma that smoking and laryngopharyngeal reflux play a role in
      recidivistic disease. Management of AO-RRP is often symptom based and includes
      lesion excision or ablation with adjuvant therapies including cidofovir for
      refractory cases. CONCLUSIONS AND RELEVANCE: Recurrent respiratory papillomatosis
      may be related to a new or latent HPV infection, potentially obtained at birth,
      and the mechanism(s) underlying the progression from HPV infection to RRP remains
      unknown. Recommendations with regard to sexual practices in patients with AO-RRP
      cannot be made at this time. Unlike human immunodeficiency virus, patients with
      AO-RRP are not obligated to discuss infection status with partners. Despite the
      nebulous nature of the disease, clinicians should be a resource to discuss the
      current state of the literature with both the patient and partner.

PMID- 25393902
TI  - The Use of a Polyetheretherketone (PEEK) Implant to Reconstruct the Midface
      Region.
AB  - A good functional and cosmetic result after midfacial reconstructive surgical
      procedures is of paramount importance. We describe the use of a
      Polyetheretherketone (PEEK) implant to reconstruct the midface area, after
      extensive mutilating surgery due to an infiltrative skin tumor. A 67-year-old
      male patient underwent multiple and extensive surgeries to the left cheek and
      lower lid because of a highly aggressive metatypical basal cell carcinoma.
      Complete resection of the recurrent tumor resulted in a cosmetically evident
      absent cheek contour and facial deformity. The PEEK implant was used to restore
      the bony cheek contour, with good aesthetic outcome and restoration of the facial
      symmetry. Preoperative planning with 3-dimensional CT scans allow for
      customization of the implant. PEEK implants have been scantily described in the
      periorbital region. The material has a very low reported morbidity and also has
      the advantage of improving intraoperative predictability and reducing surgical
      time in complex reconstructive procedures.

PMID- 25393903
TI  - Assessment of Office-Based Practice Patterns on Protective Eyewear Counseling for
      Patients With Monocular Vision.
AB  - PURPOSE: To investigate the practice patterns of office-based counseling on the
      importance of protective eyeglasses in monocular patients and to offer our
      counseling recommendations. METHODS: In this cross-sectional study, data were
      collected in the form of surveys. Surveys were administered at an oculoplastic
      ophthalmology clinic in Michigan. Inclusion criteria included adults with vision
      of 20/400 or worse in only 1 eye. Survey questions were focused on whether
      patients with monocular vision recall being previously counseled by their primary
      ophthalmologist about wearing eye protection. RESULTS: A total of 60 surveys were
      completed. The average age was 62.2 years old (range: 23-90 years old). Of the
      completed surveys, 56.7% (34/60) did not recall receiving education about wearing
      protective glasses over their better seeing eye, while 35.0% (21/60) recalled
      having received education from their referring ophthalmologist about eye
      protection, and 8.3% (5/60) were uncertain about receiving eye protection
      counseling. Twenty (33.3%) patients reported the reason for decreased vision. Of
      those, 35% (7/20) of patients reported monocular vision resulting from trauma,
      while 65% (13/20) reported vision loss due to other reasons. There was no
      significant difference in recall of receiving counseling about the importance of
      eye protection between the 2 groups (p = 0.74). CONCLUSIONS: The results of this
      study highlight the current counseling short-comings, as more than half (56.7%)
      of patients surveyed did not recall being counseled on the importance of
      protecting their better seeing-eye, or ways of doing so. More counseling on
      protective eyewear needs to be incorporated into the preferred practice pattern
      for care of patients with monocular visual impairment because these patients are
      vulnerable to the devastating consequences of complete blindness as a result of
      an injury to their functioning eye.

PMID- 25393904
TI  - Small-incision frontalis muscle transposition flap for lateral eyebrow ptosis
      repair.
AB  - PURPOSE: To describe a novel technique to correct lateral eyebrow ptosis using a
      frontalis muscle transposition flap. METHODS: The charts of all patients
      undergoing eyebrow ptosis repair using a frontalis muscle transposition flap from
      December 2013 through April 2014 were reviewed to describe the surgical
      technique. RESULTS: Sixteen patients underwent eyebrow ptosis repair using a
      frontalis muscle pedicle flap during the study period. Briefly, after local
      infiltration, a lateral forehead rhytid was marked and incised for approximately
      1.5 cm. Blunt dissection exposed the frontalis-orbicularis angle, the frontalis
      orbicularis insertion, and the lateral extent of the frontalis muscle. A pedicle
      flap of lateral frontalis muscle was created, trimmed, and transposed laterally
      in graded fashion to achieve the optimal eyebrow height and contour. The incision
      was closed with 5-0 polypropylene suture. All patients reported improvement in
      eyebrow position. CONCLUSIONS: This novel technique provides frontalis muscle
      elevatory force to the lateral eyebrow through a small incision to improve
      eyebrow ptosis. Further study, including objective measures of long-term results,
      is required.

PMID- 25393905
TI  - Nodular Fasciitis of the Orbit.
AB  - A 13-month-old boy was presented with new onset proptosis of the right eye. CT
      scan and MRI showed an enhancing mass in the right superior orbit with local bone
      remodeling and erosion. A craniotomy was performed for biopsy and sub-total
      resection. Histopathology and immunohistochemistry confirmed the lesion to be
      nodular fasciitis. Nodular fasciitis lesions are classically found in the
      anterior ocular adnexa, especially in pediatric patients. This is the first
      reported case of nodular fasciitis arising in the posterior orbit of a child
      younger than 16.

PMID- 25393906
TI  - Foreign Body Granuloma Following Orbital Reconstruction with Porous Polyethylene.
AB  - Porous polyethylene is commonly used in the orbit for fracture repair and
      anophthalmic reconstruction; it reportedly has a good safety profile and
      integrates well into host tissue. Foreign body reaction to porous polyethylene
      has been reported in facial tissue, but to our knowledge, not in the orbit. The
      authors report 2 cases of foreign body inflammatory giant cell reaction in
      patients who underwent orbital fracture repairs with porous polyethylene
      implants.

PMID- 25393907
TI  - Unilateral Prostaglandin-Associated Periorbitopathy: A Syndrome Involving Upper
      Eyelid Retraction Distinguishable From the Aging Sunken Eyelid.
AB  - PURPOSE: To study the effects of prostaglandin analogue drops on the eyelids and
      adnexa in unilaterally treated subjects with the intention of qualifying,
      quantifying, and categorizing the characteristics of prostaglandin-associated
      periorbitopathy (PAP). METHODS: Patients using prostaglandin analogue drops in
      only 1 eye for at least 1 year were evaluated by masked examiners. Orbital and
      eyelid measurements were obtained for each patient, and adnexal photographs were
      taken. PAP was divided into 3 grades based on the presence and severity of fat
      atrophy and the existence and depth of superior sulcus deformity. Statistical
      analysis was performed comparing data between treated and untreated eyes.
      RESULTS: Thirty-three patients meeting eligibility criteria were enrolled, with
      equal numbers of subjects using latanoprost, travoprost, and bimatoprost. Treated
      eyes had a statistically significant increase in lagophthalmos (0.62 mm, p <
      0.001), superior sulcus deformity/PAP grade (0.72, p < 0.001), and eyelid redness
      (1.08, p < 0.001). Treated eyes had significantly greater marginal reflex
      distance 1 measurements (0.89 mm, p = 0.02), highest with bimatoprost and
      moderate PAP. Treated eyes had relatively greater enophthalmos than untreated
      eyes. Very few patients noticed or complained about eyelid changes. CONCLUSION:
      Prostaglandin analogue drops cause adnexal changes and orbital fat atrophy
      leading to eyelid redness, superior sulcus deformity, higher eyelid crease, and
      enophthalmos. In contrast to previous studies showing ptosis in PAP, relative
      upper eyelid retraction was seen in most of our treated eyes. Our novel PAP
      grading scale may help objectify and categorize this syndrome. Awareness of these
      signs is critical, as the eyelids and eyes may be affected even in the absence of
      patient recognition.

PMID- 25393908
TI  - C-Reactive Protein As a Marker for Initiating Steroid Treatment in Children With
      Orbital Cellulitis.
AB  - PURPOSE: To determine both the benefit of systemic steroids in pediatric patients
      with orbital cellulitis and to assess the usefulness of C-reactive protein (CRP)
      levels as a marker for starting steroids. METHODS: Prospective, comparative
      interventional study. Pediatric patients aged 1 to 18 years admitted to a
      tertiary care children's hospital with a diagnosis of orbital cellulitis from
      October 2012 to March 2014 were included in the study. All patients were treated
      with intravenous antibiotics, and patients with subperiosteal abscess who met
      previously published criteria for surgical decompression underwent combined
      transorbital drainage and/or endoscopic sinus surgery. CRP was measured daily as
      a biomarker of inflammation, and when below 4 mg/dl, patients were started on
      oral prednisone 1 mg/kg per day for 7 days. Patients whose families did not
      consent to steroid treatment served as the control group. Patients were followed
      after discharge until symptoms resolved and all medications were discontinued.
      RESULTS: Thirty-one children were diagnosed with orbital cellulitis during the
      study period. Of these 31 children, 24 received oral steroids (77%) and 7 did not
      (23%). There were 19 males and 5 females in the steroid group with an average age
      of 8.1 years, and 6 males and 1 female in the nonsteroid group with an average
      age of 7.1 years (p = 0.618). Thirteen patients (54%) in the steroid group and 2
      patients (29%) in the nonsteroid group underwent sinus surgery with or without
      orbitotomy (p = 0.394). The average CRP at the onset of steroid treatment was 2.8
      mg/dl (range: 0.5-4). Patients who received oral steroids were admitted for an
      average of 3.96 days. In comparison, patients who did not receive steroids were
      admitted for an average of 7.17 days (p < 0.05). Once CRP was <=4 mg/dl, patients
      treated with steroids remained in the hospital for another 1.1 days, while
      patients who did not receive steroids remained hospitalized for another 4.9 days
      (p < 0.01). In the steroid group, 2 families reported increased hyperactivity in
      their children while on steroids. There was 1 case in each group of recurrence of
      symptoms after discharge from the hospital. Average follow-up time was 2.4 months
      in the steroid group and 2 months in the nonsteroid group (p = 0.996). At last
      visit, all patients returned to their baseline ophthalmic examination. There were
      no cases of vision loss or permanent ocular disability in either group.
      CONCLUSIONS: Our results give further evidence of the safety and benefit of
      systemic steroids in children with orbital cellulitis. Futhermore, this is the
      first study to suggest a standardized starting point (CRP <= 4 mg/dl) and dosing
      schedule (oral prednisone 1 mg/kg for 7 days) for children with orbital
      cellulitis. Patients who received systemic steroids after CRP dropped below 4
      mg/dl were discharged from the hospital earlier than patients who did not receive
      systemic steroids.

PMID- 25393909
TI  - Family Communication about Donor Conception: A Qualitative Study with Lesbian
      Parents.
AB  - In this qualitative study of 10 lesbian couples who built their families through
      anonymous donor conception, we explore how lesbian parents experience
      communication about the donor conception within the family. While for these
      families "disclosure" of donor conception is often seen as evident, the way
      parents and children discuss this subject and how this is experienced by the
      parents themselves has not received much research attention. To meet this gap in
      the literature, in-depth interviews with lesbian couples were conducted. An
      Interpretative Phenomenological Analysis showed that this family communication
      process can be understood within the broader relational context of parent-child
      relationships. Even though parents handled this family communication in many
      different ways, these were all inspired by the same motives: acting in the
      child's best interest and-on a more implicit level-maintaining good relations
      within the family. Furthermore, parents left the initiative for talking about the
      DC mostly to the child. Overall, parents aimed at constructing a donor conception
      narrative that they considered acceptable for both the children and themselves.
      They used different strategies, such as gradual disclosure, limiting the meaning
      of the donor, and justifying the donor conception. Building an acceptable donor
      conception narrative was sometimes challenged by influences from the social
      environment. In the discussion, we relate this qualitative systemic study to the
      broader issues of selective disclosure and bidirectionality within families. 

PMID- 25393911
TI  - Algebraic method to synthesize specified modal currents in ladder resonators:
      Application to noncircular birdcage coils.
AB  - PURPOSE: Detectors such as birdcage coils often consist of networks of coupled
      resonant circuits that must produce specified magnetic field distributions. In
      many cases, such as quadrature asymmetric insert body coils, calculating the
      capacitance values required to achieve specified currents and frequencies
      simultaneously is a challenging task that previously had only approximate or
      computationally inefficient solutions. THEORY AND METHODS: A general algebraic
      method was developed that is applicable to linear networks having planar
      representations such as birdcage coils, transverse electromagnetic (TEM) coils,
      and numerous variants of ladder networks. Unlike previous iterative or
      approximate methods, the algebraic method is computationally efficient and
      determines current distribution and resonant frequency using a single matrix
      inversion. The method was demonstrated by specifying irregular current
      distributions on a highly elliptical birdcage coil at 3 Tesla. RESULTS:
      Measurements of the modal frequency spectrum and transmit field distribution of
      the two specified modes agrees with the theory. Accuracy is limited in practice
      only by how accurately the matrix of self and mutual inductances of the network
      is known. CONCLUSION: The algebraic method overcomes the inability of the
      existing inductance equalization method to account for all elements of the
      inductance matrix and the inability to accommodate modal currents that are not
      (co)sinusoidal.

PMID- 25393913
TI  - FeCl3/ZnI2-catalyzed synthesis of benzo[d]imidazo[2,1-b]thiazole through aerobic
      oxidative cyclization between 2-aminobenzothiazole and ketone.
AB  - The FeCl3/ZnI2-catalyzed aerobic oxidative cyclization between 2
      aminobenzothiazole and ketone/chalcone for the synthesis of benzo[d]imidazo[2,1
      b]thiazole is described. A variety of fused benzoimidazothiazole derivatives are
      obtained by this protocol. 

PMID- 25393912
TI  - Segregated labeling of olfactory bulb projection neurons based on their
      birthdates.
AB  - Mitral and tufted cells are the projection neurons of the olfactory bulb (OB). We
      previously reported that somata location and innervation patterns were different
      between early- and late-born mitral cells (Imamura et al., 2011). Here, we
      introduced a plasmid that drives the expression of a GFP gene into the mouse OB
      using in utero electroporation, and demonstrated that we can deliver the plasmid
      vectors into distinct subsets of OB projection neurons by changing the timing of
      electroporation after fertilisation. The electroporation performed at embryonic
      day (E)10 preferentially labeled mitral cells in the accessory OB and main OB
      mitral cells in dorsomedial mitral cell layer (MCL). In contrast, the E12
      electroporation introduced the plasmid vectors preferentially into main OB mitral
      cells in the ventrolateral MCL and tufted cells. Combining these data with BrdU
      injections, we confirmed that E10 and E12 electroporation preferentially labeled
      early- and late-born projection neurons, respectively. This work introduces a
      novel method for segregated labeling of mouse olfactory bulb projection neurons
      based on their birthdates. With this technique we found that early- and late-born
      projection neurons extend their secondary dendrites in the deep and superficial
      external plexiform layer (EPL), respectively. Although a similar segregation has
      been suggested for mitral vs. tufted cell dendrites, we found mitral cells
      projecting secondary dendrites into the superficial EPL in E12-electroporated
      main OB. Our observations indicate that timing of neurogenesis regulates not only
      somata location and innervation patterns but also the laminar organisation of
      projection neuron dendrites in the EPL.

PMID- 25393914
TI  - Childcare arrangements and infant feeding practices by family structure and
      household income among US children aged 0 to 2 years.
AB  - The primary objective of this study is to examine the disparities in childcare
      and infant feeding practices by family structure (single-mother vs. two-parent
      households) and whether household income level may modify the observed
      associations by family structure. The cross-sectional data analysis was conducted
      using a nationally representative sample of children aged 0 to 2 years enrolled
      in the 2007 National Survey of Children's Health. The analytic sample is children
      from single mothers (n = 1801, 16.0%) and children from two parents (n = 11 337,
      84.0%). Children of single mothers used more non-parental childcare [adjusted
      odds ratios (AOR) = 2.67, 95% confidence intervals (CI) = 1.99-3.58], especially
      relative care and centre care, than children of two parents. Lower rates of any
      breastfeeding for 6 months (AOR = 0.57, 95% CI = 0.43-0.77) and ever breastfed
      (AOR = 0.66, 95% CI = 0.50-0.89) were reported among children of single mothers
      than those of two parents. The many observed differences in childcare
      arrangements and breastfeeding by family structure remained significant in both
      low- and high-income households. However, children of low-income single mothers
      had more last-minute changes of childcare arrangement (AOR = 2.34, 95% CI = 1.55
      3.52) than children of low-income two-parent households and children of high
      income single mothers had more early introduction of complementary foods (AOR =
      1.92, 95% CI = 1.12-3.29) than children of high-income two-parent households.
      This study documented disparities in childcare arrangements and infant feeding
      practices by family structure, regardless of income level. These findings support
      the need to for comprehensive policies that address maternal employment leave,
      childcare support and workplace accommodations and support for breastfeeding for
      children 0 to 2 years, especially among single mothers, regardless of income.

PMID- 25393910
TI  - The translation inhibitor silvestrol exhibits direct anti-tumor activity while
      preserving innate and adaptive immunity against EBV-driven lymphoproliferative
      disease.
AB  - Treatment options for patients with Epstein-Barr Virus-driven lymphoproliferative
      diseases (EBV-LPD) are limited. Chemo-immunotherapeutic approaches often lead to
      immune suppression, risk of lethal infection and EBV reactivation, thus it is
      essential to identify agents that can deliver direct anti-tumor activity while
      preserving innate and adaptive host immune surveillance. Silvestrol possesses
      direct anti-tumor activity in multiple hematologic malignancies while causing
      minimal toxicity to normal mononuclear cells. However, the effects of silvestrol
      on immune function have not been described. We utilized in vitro and in vivo
      models of EBV-LPD to simultaneously examine the impact of silvestrol on both
      tumor and normal immune function. We show that silvestrol induces direct anti
      tumor activity against EBV-transformed lymphoblastoid cell lines (LCL), with
      growth inhibition, decreased expression of the EBV oncogene latent membrane
      protein-1, and inhibition of the downstream AKT, STAT1 and STAT3 signaling
      pathways. Silvestrol promoted potent indirect anti-tumor effects by preserving
      expansion of innate and EBV antigen-specific adaptive immune effector subsets
      capable of effective clearance of LCL tumor targets in autologous co-cultures. In
      an animal model of spontaneous EBV-LPD, silvestrol demonstrated significant
      therapeutic activity dependent on the presence of CD8-positive T-cells. These
      findings establish a novel immune-sparing activity of silvestrol, justifying
      further exploration in patients with EBV-positive malignancies. 

PMID- 25393915
TI  - Effectiveness of Telemedicine for Controlling Asthma Symptoms: A Systematic
      Review and Meta-analysis.
AB  - BACKGROUND: The effectiveness of telemedicine for the management of chronic
      diseases is unclear. This study examined the effectiveness of telemedicine in
      relieving asthma symptoms. MATERIALS AND METHODS: A systematic review of the
      Medline, Cochrane, EMBASE, and Google Scholar databases was conducted until
      December 31, 2013 using the following key words: "asthma," "telemedicine,"
      "telehealth," "e-health," "mobile health," "Internet," "telecommunication,"
      "telemanagement," "remote," and "short message service." Inclusion criteria were
      randomized controlled trial, a diagnosis of asthma, the majority of the patients
      were >=18 years of age, and intervention involved any format of telemedicine. A
      meta-analysis of eligible studies was conducted with the primary outcome being
      change of asthma symptoms. RESULTS: Of 813 articles identified, 11 were included
      in the qualitative synthesis, and 6 were included in the meta-analysis. Among the
      11 studies, there were 1,460 patients in the intervention groups and 1,349 in the
      control groups, and the total numbers of participants ranged from 12 to 481 in
      the intervention groups and from 12 to 487 in the control groups. The mean age of
      patients ranged in the intervention groups from 34.4 to 54.6 years and in the
      control groups from 30.7 to 56.4 years. The treatment duration ranged from 0.5 to
      12 months. The meta-analysis of six eligible studies revealed no significant
      difference in asthma symptom score change between the telemedicine and control
      groups (pooled Hedges's g=0.34, 95% confidence interval=-0.05 to 0.74, Z=1.69,
      p=0.090). CONCLUSIONS: Telemedicine interventions do not appear to improve asthma
      function scores, but other benefits may be present.

PMID- 25393917
TI  - Editorial: microbes and insects.

PMID- 25393916
TI  - Clinical value and safety of liver biopsies in patients transplanted for
      hepatitis C virus-related end-stage liver disease.
AB  - BACKGROUND: Hepatitis C is the leading indication for liver transplantation.
      Differentiation between recurrent graft hepatitis C (RGH-C) and graft rejection
      (GR) is challenging. Liver biopsy is standard to diagnose both conditions;
      however, little information is available regarding this procedure in hepatitis C
      virus (HCV)-infected liver transplant recipients. METHODS: Liver biopsies (n =
      211) from all consecutive patients (n = 138) transplanted for hepatitis C at
      Hannover Medical School between January 2000 and October 2011 were screened, and
      a final cohort of 96 patients with 196 biopsies was included. Indications,
      histopathological findings, and biopsy-related complications were documented.
      Modifications in the treatment based on the biopsy result and the biochemical
      outcome were analyzed. RESULTS: Most biopsies (196/211, 93%) were representative.
      Five patients (2.5%) developed non-fatal biopsy-related complications. Biopsy
      results were GR (35%), RGH-C (31%), and other diagnoses (34%). GR was
      independently associated with lower albumin (P = 0.025) and higher bilirubin
      levels (P = 0.011). Treatment was modified based on the biopsy result in 25% of
      cases. Alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and
      bilirubin levels improved in 41%, 25%, and 31% of cases 4 weeks post biopsy
      respectively. ALT improvements were more significant in patients with GR than in
      those with RGH-C. CONCLUSION: Liver biopsy in HCV-infected liver transplant
      recipients is safe and representative in >90% of cases. GR is independently
      associated with lower albumin and higher bilirubin levels.

PMID- 25393920
TI  - Atmospheric pressure plasma treatment of black peppercorns inoculated with
      Salmonella and held under controlled storage.
AB  - Spices, including black pepper, are a source of microbial contamination and have
      been linked to outbreaks of salmonellosis when added to products that undergo no
      further processing. Traditional thermal processing employed to reduce microbial
      contamination can lead to losses of heat-sensitive compounds. Thus, alternative
      processes such as atmospheric pressure plasma (APP) are desirable. The purpose of
      this research was to determine the efficacy of APP in the destruction of
      Salmonella inoculated on the surface of peppercorns. Secondarily, we examined the
      effect of storage on the subsequent inactivation of Salmonella on the surfaces of
      black peppercorns by APP. Black peppercorns inoculated with a cocktail of
      Salmonella enterica serotypes Oranienburg, Tennessee, Anatum, and Enteritidis
      were stored at 25  degrees C, 33% relative humidity (RH); 25  degrees C, 97% RH;
      and, 37  degrees C, 33% RH for 10 d and additionally at 25  degrees C, 33% RH for
      1 and 30 d then treated with APP. Results showed that Salmonella populations
      decreased significantly (P < 0.05) with respect to the treatment time, but where
      not related to previous storage conditions (P > 0.05). Approximately a 4.5- to
      5.5-log10 reduction in population was achieved after 60 to 80 s treatment. A
      combination of treatments, storage and 80 s of plasma, may achieve a total
      reduction on the order of 7-log10 CFU/g. These findings support the potential of
      APP to decontaminate Salmonella on the surfaces of black peppercorns and other
      dry foods and illustrate that a multiple hurdle approach may prove effective for
      achieving significant reductions of Salmonella in many low-moisture foods. 

PMID- 25393921
TI  - Hypofractionated radiation therapy for the treatment of microscopic canine soft
      tissue sarcoma.
AB  - Soft tissue sarcomas (STSs) are locally invasive and surgery with or without
      radiation therapy is the current standard of care in dogs. Typical protocols for
      treating incompletely excised STSs involve curative intent radiation with total
      dose in excess of 50 Gy. Forty-eight dogs with histologically confirmed
      incomplete or closely excised STSs were treated with a hypofractionated protocol
      that is typically reserved for palliative radiation therapy (RT) (6-8 Gy/weekly
      fractions to a total dose of 24-32 Gy). Ten dogs (21%) developed local
      recurrence, 11 dogs (23%) developed metastasis, and 3 dogs developed both
      (included in each group). The median progression free survival was 698 days. The
      local failure-free probability at 1 and 3 years was 81 and 73%. The 1 and 3 years
      tumour-specific overall survival was 81 and 61%. Long-term local tumour control
      was achieved in the majority of dogs. This protocol is reasonable to prescribe in
      older patients or when financial limitations exist.

PMID- 25393922
TI  - Cardiac biomarkers indicate a need for sensitive cardiac imaging among long-term
      childhood cancer survivors exposed to anthracyclines.
AB  - AIM: The role that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP)
      and cardiac troponins T (cTnT) and I (cTnI) play in supplementing imaging to
      screen for cardiac late effects remains controversial and the impact of high
      sensitivity cTnT and troponin-specific autoantibodies (cTnAAbs) remains
      unexplored. We studied the role of cardiac biomarkers as indicators of the late
      effects of anthracyclines among childhood cancer survivors. METHODS: We measured
      NT-proBNP, cTnT, high-sensitivity cTnT, cTnI and cTnAAbs in 76 childhood cancer
      survivors at a median of 9 years after primary diagnosis. The survivors underwent
      conventional and real-time three-dimensional echocardiography and 62 underwent
      cardiac magnetic resonance imaging (MRI). RESULTS: Of the survivors, four (5.3%)
      without risk factors for cardiotoxicity were cTnAAb-positive with an impaired
      cardiac function in MRI. Another four (5.3%) had an abnormal NT-proBNP level
      associated with an abnormal cardiac function and risk factors for cardiotoxicity.
      None showed measurable cardiac troponins, determined by the three different
      methods, with even the high-sensitivity cTnT-levels remaining normal. CONCLUSION:
      Elevated plasma NT-proBNP or cTnAAbs indicated that childhood cancer survivors
      benefitted from being evaluated with modern imaging, despite normal function in
      conventional echocardiography. However, troponins did not seem to provide
      additional information on the late cardiotoxicity of anthracyclines.

PMID- 25393923
TI  - A coverage criterion for spaced seeds and its applications to support vector
      machine string kernels and k-mer distances.
AB  - Spaced seeds have been recently shown to not only detect more alignments, but
      also to give a more accurate measure of phylogenetic distances, and to provide a
      lower misclassification rate when used with Support Vector Machines (SVMs). We
      confirm by independent experiments these two results, and propose in this article
      to use a coverage criterion to measure the seed efficiency in both cases in order
      to design better seed patterns. We show first how this coverage criterion can be
      directly measured by a full automaton-based approach. We then illustrate how this
      criterion performs when compared with two other criteria frequently used, namely
      the single-hit and multiple-hit criteria, through correlation coefficients with
      the correct classification/the true distance. At the end, for alignment-free
      distances, we propose an extension by adopting the coverage criterion, show how
      it performs, and indicate how it can be efficiently computed.

PMID- 25393924
TI  - Functional response, host stage preference and interference of two whitefly
      parasitoids.
AB  - The functional responses of two parasitoids, Eretmocerus hayati Zolnerowich &
      Rose and Encarsia sophia Girault & Dodd, of whitefly Bemisia tabaci Gennadius
      Middle East-Asia Minor 1 were studied under laboratory conditions. In addition,
      the influence of host density and host stage on the competitive interactions
      between the two parasitoids, and biological control effect on whitefly were
      evaluated. In the functional response study, adult parasitoids were tested
      individually, with a conspecific or heterospecific competitor. Both Er. hayati
      and En. sophia exhibited a type II response to increasing host density, whether a
      conspecific or heterospecific competitor was present or not. Difference of
      searching rates and handling times between treatments suggested interference
      interactions existed between two parasitoid species. In the host stage preference
      study, two parasitoid species were jointly tested. Er. hayati had a competitive
      advantage over En. sophia when provided young host instars (first and second
      instar), whereas no advantage was found on old host instars (third and fourth
      instar). The biological control effect of Er. hayati and En. sophia in different
      introductions varied with host density. However, the effect of host instar on
      host mortality was not significant. These findings provide information for the
      practice of biological control and give better insight into how parasitoid
      species may coexist in diverse environments. 

PMID- 25393925
TI  - Is combination therapy for resistant vitreous seeds really essential?

PMID- 25393926
TI  - Highly enantioselective intramolecular 1,3-dipolar cycloaddition: a route to
      piperidino-pyrrolizidines.
AB  - Enantioselective catalytic intermolecular 1,3-dipolar cycloadditions are powerful
      methods for the synthesis of heterocycles. In contrast, intramolecular
      enantioselective 1,3-dipolar cycloadditions are virtually unexplored. A highly
      enantioselective synthesis of natural-product-inspired pyrrolidino-piperidines by
      means of an intramolecular 1,3-dipolar cycloaddition with azomethine ylides is
      now reported. The method has a wide scope and yields the desired cycloadducts
      with four tertiary stereogenic centers with up to 99% ee. Combining the
      enantioselective catalytic intramolecular 1,3-dipolar cycloaddition with a
      subsequent diastereoselective intermolecular 1,3-dipolar cycloaddition yielded
      complex piperidino-pyrrolizidines with very high stereoselectivity in a one-pot
      tandem reaction.

PMID- 25393927
TI  - Primary packaging considerations in developing medicines for children: oral
      liquid and powder for constitution.
AB  - The packaging presentation of oral liquid pediatric medicines is a critical step
      in maintaining chemical and physical stability, compliance, adherence, and proper
      handling by the target patient population, guardians, caregivers, and health-care
      professionals. The common packaging presentations for commercial oral liquid
      pediatric drug products are glass bottle, plastic bottle, sachet, and stick pack
      configurations. The type of pack presentation selected is driven by the quality
      target product profile (QTPP) that is designed around the physicochemical
      properties of the drug substance and the desired drug product suitability for the
      target population. The QTPP defines the intended use of the drug product, drug
      product quality criteria, dose strength, dosage form, container closure system,
      storage conditions, stability criteria, dosing device, shelf life, and attributes
      affecting the pharmacokinetic characteristics. Oral liquid pediatric formulations
      are typically prepared from a powder that is constituted at the time of use as a
      suspension or a solution for single or multiple use depending on the stability of
      the constituted formulation. Active ingredients with high aqueous solubility can
      be developed as a powder for oral solution and presented in a bottle for multiple
      use product and a stick pack, packet, or sachet for single-use product. Active
      ingredients with low aqueous solubility can be developed as a powder for oral
      suspension and presented in a bottle for multiple use product and a stick pack or
      sachet for single-use product. A secondary package may be used in cases where the
      primary pack failed to provide adequate protection against light degradation.
      This work will help formulation scientists select the most appropriate pack
      presentation in the early stages of pediatric clinical development.

PMID- 25393928
TI  - A method for prioritizing interventions following root cause analysis (RCA):
      lessons from philosophy.
AB  - RATIONALE, AIMS AND OBJECTIVES: Root cause analysis (RCA) is widely used to
      investigate adverse events in health care and is mandated by many organizations
      and governments. RCA employs a combination of techniques to establish the factors
      contributing to a harmful outcome. Once the factors are identified, then
      interventions are usually designed in order to prevent further harms from
      occurring. Prior to deciding which intervention(s) to implement, we must make
      judgements of causal importance in the context of multiple, interacting
      conditions. Clearly, we must take action to prevent adverse events, but we need
      not take action against every contributing cause. I aim to show that many causal
      factors can be identified by RCA, but current approaches do not adequately
      distinguish among these causes, leaving numerous potential targets of
      intervention. I argue that this is because the literature on RCA (with few
      exceptions) has largely neglected the literature on philosophy of causation and
      explanation. METHOD: In this paper, I focus on demonstrating how Strevens'
      kairetic approach to explanation and Tinbergen's four questions to explain
      behaviour have the potential to work synergistically with the present RCA
      methods. RESULT: There are important lessons we can bring to RCA from the
      literature on causation and explanation, particularly from the philosophy of
      science and biology. CONCLUSION: This work could enhance the effectiveness of RCA
      by identifying and understanding the causes that really make a difference to
      adverse events. This ought to reduce the number of targets and focus intervention
      following RCA.

PMID- 25393929
TI  - Efficient sugar release by acetic acid ethanol-based organosolv pretreatment and
      enzymatic saccharification.
AB  - Acetic acid ethanol-based organosolv pretreatment of sugar cane bagasse was
      performed to enhance enzymatic hydrolysis. The effect of different parameters
      (including temperature, reaction time, solvent concentration, and acid catalyst
      dose) on pretreatment prehydrolyzate and subsequent enzymatic digestibility was
      determined. During the pretreatment process, 11.83 g of xylose based on 100 g of
      raw material could be obtained. After the ethanol-based pretreatment, the
      enzymatic hydrolysis was enhanced and the highest glucose yield of 40.99 g based
      on 100 g of raw material could be obtained, representing 93.8% of glucose in
      sugar cane bagasse. The maximum total sugar yields occurred at 190  degrees C, 45
      min, 60:40 ethanol/water, and 5% dosage of acetic acid, reaching 58.36 g
      (including 17.69 g of xylose and 40.67 g of glucose) based on 100 g of raw
      material, representing 85.4% of total sugars in raw material. Furthermore,
      characterization of the pretreated sugar cane bagasse using X-ray diffraction and
      scanning electron microscopy analyses were also developed. The results suggested
      that ethanol-based organosolv pretreatment could enhance enzymatic
      digestibilities because of the delignification and removal of xylan. 

PMID- 25393930
TI  - Balancing immunity and tolerance: genetic footprint of natural selection in the
      transcriptional regulatory region of HLA-G.
AB  - Human leukocyte antigen-G (HLA-G) has well-recognized immunosuppressive
      properties modulating the activity of many immune system cells, and polymorphisms
      observed at the HLA-G 5' upstream regulatory region (5'URR) may influence gene
      transcriptional regulation. In this study, we characterized the sequence
      variation and haplotype structure of the HLA-G 5'URR in worldwide populations to
      investigate the evolutionary history of the HLA-G promoter and shed some light
      into the mechanisms that may underlie HLA-G expression control. A 1.4-kb region,
      encompassing the known HLA-G regulatory elements, was sequenced in three African
      populations from Senegal, Benin and Congo, and data were combined with those
      available in the literature, resulting in a total of 1411 individuals from 21
      worldwide populations. High levels of nucleotide and haplotype diversities,
      excess of intermediate-frequency variants and reduced population differentiation
      were observed at this locus when compared with the background genomic variation.
      These features support a strong molecular signature of balancing selection at HLA
      G 5'URR, probably as a result of the competing needs to maintain both a maternal
      fetal immune tolerance and an efficient host immune response to invading
      pathogens during human evolution. An extended analysis of a 300-kb region
      surrounding HLA-G revealed that this region is not involved in a hitchhiking
      effect and may be the direct target of selection. 

PMID- 25393932
TI  - Effects of palm and sunflower oils on serum cholesterol and fatty liver in rats.
AB  - Palm oil is a common cooking ingredient used in the commercial food industry as
      the second largest consumed vegetable oil in the world. Because of its lower cost
      and highly saturated nature, it usually maintains a solid form at room
      temperature and is used as a cheap substitute for butter. However, there has been
      a growing health concern about palm oil because of the link between dietary fats
      and coronary heart disease. Palm oil contains ~49% saturated fat, a relatively
      high concentration compared with other vegetable oils. Consequently, high intakes
      of saturated fat from palm oil induce a larger increase in plasma concentrations
      of total cholesterol and low-density lipoproteins. In the present study, we
      examined the hyperlipidemia of palm oil and the risk of cardiovascular disease
      (CVD) using a rat model in comparison with sunflower oil with a relatively low
      level of saturated fat. On in vivo examination using Sprague-Dawley (SD) rats for
      22 days, there were no significant differences in serum lipid levels, suggesting
      that palm oil may not cause hyperlipidemia and elevate CVD risk. However, liver
      samples obtained from SD rats fed with palm oil showed a lot of large lipid
      inclusions stained with the Oil Red O working solution, but not much lipid
      accumulation was observed in rats treated with sunflower oil. In addition, lipid
      accumulation in the mixed oil group fed the combination of palm and sunflower
      (1:1) oil was shown to be at an intermediary level between the palm oil group and
      sunflower oil group. Taken together, these results indicate that palm oil, a
      highly saturated form of vegetable oil, may induce dysfunction of the liver lipid
      metabolism before affecting serum lipid levels. On the other hand, sunflower oil,
      a highly unsaturated vegetable oil, was shown to be well metabolized in liver. 

PMID- 25393931
TI  - Methylation of NKG2D ligands contributes to immune system evasion in acute
      myeloid leukemia.
AB  - Engagement of the activating receptor NKG2D (natural killer group 2 member D)
      with its ligands (NKG2DL) major histocompatibility complex class I related-A and 
      B (MICA/B), UL-16 binding protein families (ULBPs 1-6) is important to ensure the
      innate immunity to tumor cells. However, these cells have developed strategies to
      downregulate NKG2DL expression and avoid immune recognition. We demonstrate that
      DNA methylation can contribute to the absence of NKG2DL expression during tumor
      progression. We analyzed the DNA methylation profiles for each NKG2DL by
      pyrosequencing in acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL),
      hepatocellular carcinoma (HC), breast cancer and colon cancer cell lines. High
      levels of DNA methylation for NKG2DL were found in some tumor cell lines, mainly
      in AML cells. This hypermethylation was correlated with the absence of
      transcription for NKG2DL. Higher DNA methylation levels for MICA, ULBP1 and ULBP2
      were observed in AML patients (n=60) compared with healthy donors (n=25).
      However, no DNA methylation for NKG2DL was found in colon cancer patients (n=44).
      Treatment with demethylating agents (5-azacytidine and 5-aza-2'-deoxycytidine)
      restored the expression of NKG2DL on the cell surface of AML cells, leading to an
      enhanced recognition by NKG2D-expressing cells. Our data suggest that NKG2DL may
      be aberrantly silenced by DNA methylation as a consequence of tumor development
      in AML patients. 

PMID- 25393933
TI  - Parental perception of healthy eating and physical activity: results from a
      preliminary Photovoice study.

PMID- 25393934
TI  - Effects of overnight fasting on working memory-related brain network: an fMRI
      study.
AB  - Glucose metabolism serves as the central source of energy for the human brain.
      Little is known about the effects of blood glucose level (BGL) on higher-order
      cognitive functions within a physiological range (e.g., after overnight fasting).
      In this randomized, placebo-controlled, double blind study, we assessed the
      impact of overnight fasting (14 h) on brain activation during a working memory
      task. We sought to mimic BGLs that occur naturally in healthy humans after
      overnight fasting. After standardized periods of food restriction, 40 (20 male)
      healthy participants were randomly assigned to receive either glucagon to balance
      the BGL or placebo (NaCl). A parametric fMRI paradigm, including 2-back and 0
      back tasks, was used. Subclinically low BGL following overnight fasting was found
      to be linked to reduced involvement of the bilateral dorsal midline thalamus and
      the bilateral basal ganglia, suggesting high sensitivity of those regions to
      minimal changes in BGLs. Our results indicate that overnight fasting leads to
      physiologically low levels of glucose, impacting brain activation during working
      memory tasks even when there are no differences in cognitive performance.

PMID- 25393935
TI  - Metabolomics reveals significant impairments in the immune system of the APP/PS1
      transgenic mice of Alzheimer's disease.
AB  - Inflammatory processes and other failures related to the immune system are common
      features associated with Alzheimer's disease (AD), in both brain and the
      peripheral system. Thus, the study of the main organs of the immune system may
      have a great potential for the elucidation of pathological mechanisms underlying
      these abnormalities. This is the first metabolomic investigation performed in
      spleen and thymus from transgenic mice of AD. Tissues were fingerprinted using a
      metabolomic platform comprising GC-MS and ultra-HPLC-MS. Multivariate statistics
      demonstrated significant differences in numerous metabolites between the APP/PS1
      mice and wild-type controls, and it was proven that multiple biochemical pathways
      are disturbed in these organs including abnormal metabolism of phospholipids,
      energy deficiencies, altered homeostasis of amino acids, oxidative stress, and
      others. Therefore, these findings highlight the importance of the proper
      metabolic functioning of peripheral immune system in the development of
      neurodegenerative disorders such as AD. 

PMID- 25393936
TI  - Enhanced performance of mixed-matrix membranes through a graft copolymer-directed
      interface and interaction tuning approach.
AB  - Herein, a high performance mixed-matrix membrane (MMM) is reported with
      simultaneously large improvements in the CO2 permeability by 880 % from 70.2 to
      687.7 Barrer (1 Barrer=1*10(-10)  cm(3)  cm cm(-2)  s(-1)  cmHg(-1) ) and CO2 /N2
      selectivity by 14.4 % from 30.5 to 34.9. These findings represent one of the most
      dramatic improvements ever reported for MMMs. These improvements are obtained
      through an interface and interaction tuning approach based on an amphiphilic
      grafted copolymer. Poly(vinyl chloride)-g-poly(oxyethylene methacrylate) (PVC-g
      POEM) graft copolymer plays a key role as a soft organic matrix to provide good
      permeation properties, uniform distribution of zeolite imidazole frameworks-8
      (ZIF-8), and better interfacial contact with inorganic compounds. In particular,
      the CO2 /C3 H8 and CO2 /C3 H6 selectivities reached 10.5 and 42.7, respectively,
      for PVC-g-POEM/ZIF (40 %) MMMs; this indicates that it could be a promising
      membrane material for the purification of C3 hydrocarbons. 

PMID- 25393937
TI  - Effects of climate change on the toxicity of soils polluted by metal mine wastes
      to Enchytraeus crypticus.
AB  - The present study aimed to assess the effects of climate change on the toxicity
      of metal-polluted soils. Bioassays with Enchytraeus crypticus were performed in
      soils polluted by mine wastes (mine tailing, forest, and watercourse) and under
      different combinations of temperature (20  degrees C and 25  degrees C) and soil
      moisture content (50% and 30% of the soil water-holding capacity). Survival and
      reproduction were set as endpoints. No effect was observed on survival (average
      survival >= 80%). Reproduction was the most sensitive endpoint, and it was
      reduced between 65% and 98% compared with control after exposure to watercourse
      soil (lower pH, higher salinity, and higher available metal(loid)
      concentrations). In this soil, effective concentrations at 50% and 10% (EC50 and
      EC10) significantly decreased with decreasing soil moisture content. In general,
      the worst-case scenario was found in the driest soil, but the toxicity under a
      climate change scenario differed among soil types in relation to soil properties
      (e.g., pH, salinity) and available metal(loid) concentrations.

PMID- 25393938
TI  - Spectroscopic examinations of hydrogen bonding in hydroxy-functionalized ADMET
      chemistry.
AB  - Wide-angle X-ray scattering (WAXS) and temperature-dependent Fourier transform
      infrared spectroscopy (FTIR) spectroscopy are used to study hydrogen bonding
      interactions of a hydroxyl-functionalized polyethylene (PE) prepared by acyclic
      diene metathesis (ADMET) chemistry. The hydroxyl polymer exhibits an orthorhombic
      unit cell structure with characteristic reflection planes at (110) and (200),
      comparable to pure crystalline PE. These data unequivocally demonstrate that the
      OH branch is excluded from the PE lamellae. Furthermore, the polymer melts 100 
      degrees C higher than all previous analogous polymers possessing precision placed
      long aliphatic branches that also are excluded from PE lamellae. Temperature
      dependent FTIR spectroscopy from ambient to 150  degrees C, followed by cooling
      to 125  degrees C supports exclusion of the hydroxyl group from the crystalline
      lattice. It is concluded that these hydroxyl groups form stable physical networks
      in the amorphous region via hydrogen bonding and are important for the overall
      morphology of such polymers. 

PMID- 25393939
TI  - Antiretroviral therapy in HIV-infected elite controllers: impact on gut
      immunology, microbial translocation, and biomarkers of serious non-AIDS
      conditions.
AB  - Elite controllers (ECs) maintain undetectable HIV viral loads without
      antiretroviral therapy (ART) but are at increased risk of serious non-AIDS
      conditions (SNA). We assessed the impact of ART in ECs on gut immune dysfunction
      and biomarkers predicting SNA (blood CD4/CD8 ratio, plasma IL-6, D-dimer levels).
      At baseline, ECs had elevated IL-6 and D-dimer levels and reduced CD4/CD8 ratio
      compared with HIV-uninfected controls, but no difference in microbial
      translocation or gut CD4 subsets. ART increased CD4/CD8 ratio but did not
      normalize IL-6 and D-dimer levels. EC SNA pathogenesis may be independent of gut
      immune dysfunction, and resolution may require prolonged ART.

PMID- 25393940
TI  - Interleukin-6, high sensitivity C-reactive protein, and the development of type 2
      diabetes among HIV-positive patients taking antiretroviral therapy.
AB  - BACKGROUND: HIV infection is associated with increased levels of inflammatory
      markers. Inflammation is hypothesized to play a role in the development of type 2
      diabetes. Data addressing this issue among HIV-positive participants are limited.
      METHODS: A cohort of 3695 participants without diabetes, taking antiretroviral
      therapy and with an average CD4+ count of 523 cells/mm3, were followed for an
      average of 4.6 years. Diabetes risk associated with baseline levels of high
      sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) was assessed
      using Cox proportional hazards regression models. Analyses considered baseline
      levels of factors associated with diabetes risk and HIV-related measures.
      RESULTS: One hundred thirty-seven patients developed diabetes requiring drug
      treatment during follow-up (8.18 per 1000 person-years). Median levels of IL-6
      and hsCRP were significantly higher among those who developed diabetes compared
      with those who did not: 3.45 versus 2.50 pg/mL for IL-6 and 4.91 versus 3.29
      ug/mL for hsCRP (P < 0.001). Adjusted hazard ratios associated with a doubling of
      IL-6 and hsCRP were 1.29 (95% confidence interval: 1.08 to 1.55; P = 0.005) and
      1.22 (95% confidence interval: 1.10 to 1.36; P < 0.001), respectively. Body mass
      index (P < 0.001), age (P = 0.013), coinfection with hepatitis B or C (P = 0.03),
      nonsmoking status (P = 0.034), and use of lipid-lowering treatment (P = 0.008)
      were also associated with an increased risk of diabetes. CONCLUSIONS: These
      findings indicate that low-grade systemic inflammation is an underlying factor in
      the pathogenesis of diabetes.

PMID- 25393941
TI  - Incidence rate of Kaposi sarcoma in HIV-infected patients on antiretroviral
      therapy in Southern Africa: a prospective multicohort study.
AB  - BACKGROUND: The risk of Kaposi sarcoma (KS) among HIV-infected persons on
      antiretroviral therapy (ART) is not well defined in resource-limited settings. We
      studied KS incidence rates and associated risk factors in children and adults on
      ART in Southern Africa. METHODS: We included patient data of 6 ART programs in
      Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in
      patients on ART measuring time from 30 days after ART initiation to KS diagnosis,
      last follow-up visit, or death. We assessed risk factors (age, sex, calendar
      year, WHO stage, tuberculosis, and CD4 counts) using Cox models. FINDINGS: We
      analyzed data from 173,245 patients (61% female, 8% children aged <16 years) who
      started ART between 2004 and 2010. Five hundred and sixty-four incident cases
      were diagnosed during 343,927 person-years (pys). The overall KS incidence rate
      was 164/100,000 pys [95% confidence interval (CI): 151 to 178]. The incidence
      rate was highest 30-90 days after ART initiation (413/100,000 pys; 95% CI: 342 to
      497) and declined thereafter [86/100,000 pys (95% CI: 71 to 105), >2 years after
      ART initiation]. Male sex [adjusted hazard ratio (HR): 1.34; 95% CI: 1.12 to
      1.61], low current CD4 counts (>=500 versus <50 cells/MUL, adjusted HR: 0.36; 95%
      CI: 0.23 to 0.55), and age (5-9 years versus 30-39 years, adjusted HR: 0.20; 95%
      CI: 0.05 to 0.79) were relevant risk factors for developing KS. INTERPRETATION:
      Despite ART, KS risk in HIV-infected persons in Southern Africa remains high.
      Early HIV testing and maintaining high CD4 counts is needed to further reduce KS
      related morbidity and mortality.

PMID- 25393943
TI  - Bending nanofibers into nanospirals: coordination chemistry as a tool for shaping
      hydrophobic assemblies.
AB  - In the current work, we demonstrate how coordination chemistry can be employed to
      direct self-assembly based on strong hydrophobic interactions. To investigate the
      influence of coordination sphere geometry on aqueous self-assembly, we
      synthesized complexes of the amphiphilic perylene diimide terpyridine ligand with
      the first-row transition-metal centers (zinc, cobalt, and nickel). In aqueous
      medium, aggregation of these complexes is induced by hydrophobic interactions
      between the ligands. However, the final shapes of the resulting assemblies depend
      on the preferred geometry of the coordination spheres typical for the particular
      metal center. The self-assembly process was characterized by UV/Vis spectroscopy,
      zeta potential measurements, and cryogenic transmission electron microscopy (cryo
      TEM). Coordination of zinc(II) and cobalt(II) leads to the formation of unique
      nanospiral assemblies, whereas complexation of nickel(II) leads to the formation
      of straight nanofibers. Notably, coordination bonds are utilized not as
      connectors between elementary building blocks, but as directing interactions,
      enabling control over supramolecular geometry. 

PMID- 25393944
TI  - Field-induced multiple relaxation mechanism of Co(III)2Dy(III) compound with the
      dysprosium ion in a low-symmetrical environment.
AB  - A defective cubane-shaped heterometallic trinuclear Co(III)2Dy(III) compound with
      only one magnetically interesting ion (Dy(III)) has been assembled by virtue of a
      multifunctional acylhydrazone ligand. Because of the nonaxial ground state of
      Dy(III) ion derived from a low-symmetrical crystal field, the title compound
      displays field-induced multiple relaxation processes which are of molecular and a
      dipolar-dipolar coupling origin, as revealed by combined experimental and
      theoretical investigations. The results demonstrate that such a mononuclear
      dysprosium(III) compound with a low-symmetrical environment of magnetic center
      appears to be a model system for further investigations to shed light on the
      complex relaxation mechanism of lanthanide-based single ion magnets. 

PMID- 25393942
TI  - Perception of HIV risk and adherence to a daily, investigational pill for HIV
      prevention in FEM-PrEP.
AB  - BACKGROUND: FEM-PrEP was unable to demonstrate the effectiveness of oral
      emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as pre-exposure prophylaxis
      for HIV prevention because of low adherence. We hypothesized that one reason for
      the poor adherence was low perceived HIV risk. METHODS: At enrollment and at
      quarterly follow-up visits, we assessed participants' perceived HIV risk for the
      subsequent 4 weeks. We used logistic regression to assess factors associated with
      some (small, moderate, or high) perceived HIV risk. We also used logistic
      regression with robust variance estimation to assess the association between risk
      perceptions (none versus some) reported at enrollment and at weeks 12, 24, and 36
      and good adherence based on drug concentrations of plasma tenofovir and
      intracellular tenofovir diphosphate in specimens collected 4 weeks later (at
      weeks 4, 16, 28, and 40) among 150 randomly selected participants assigned
      FTC/TDF. RESULTS: Multiple factors were statistically associated with having some
      perceived risk, including having sex without a condom, having multiple partners,
      and not knowing if a partner has HIV. We observed a significant association
      between having some risk perception and good adherence (odds ratio: 2.0; 95%
      confidence interval: 1.1 to 3.5; P = 0.016). CONCLUSIONS: Data suggest that
      participants are likely knowledgeable about factors that increase their HIV risk.
      Perceived risk seemed to have influenced some participants' decisions to adhere
      to the study pill within the context of a placebo-controlled clinical trial.
      Future research can explore the role of risk perception in the uptake of and
      adherence to pre-exposure prophylaxis, now that FTC/TDF has been shown
      efficacious.

PMID- 25393945
TI  - Myocardial T1: quantification by using an ECG-triggered radial single-shot
      inversion-recovery MR imaging sequence.
AB  - PURPOSE: To develop and validate a fast cardiac magnetic resonance imaging T1
      mapping technique with high spatial resolution based on a radial inversion
      recovery (IR) spoiled gradient-echo acquisition. MATERIALS AND METHODS: Approval
      for the study was granted by the local institutional review board, and all
      subjects gave written informed consent. An electrocardiographically triggered
      radial single-shot IR (TRASSI) sequence was developed in conjunction with a
      custom-written fitting algorithm. The proposed imaging technique was validated in
      phantom measurements and then used for cardiac T1 mapping in 62 subjects with or
      without cardiac disease. The study population included 51 healthy subjects, three
      patients with arrhythmia, and eight patients with myocardial infarction. The
      potential heart rate dependency of the TRASSI method was tested by using linear
      regression analysis. Statistically significant differences between the sexes and
      various section orientations were analyzed with a Student t test for independent
      groups and a repeated-measures analysis of variance for dependent groups.
      RESULTS: High-spatial-resolution T1 maps (1.17 * 1.17 mm) without motion
      artifacts and without heart rate dependency (slope = -0.0303, R(2) = 0.0000887, P
      = .899) were acquired with an acquisition time of less than 6 seconds in all
      subjects. The mean T1 of healthy left ventricular myocardium across all examined
      subjects was 1031 msec +/- 33 (standard deviation). Testing for reproducibility
      in three individuals with 34 repetitive measurements revealed a mean standard
      deviation of 4.1 msec (0.412%). Subacute and chronic myocardial infarction could
      be detected in all eight patients. T1 disturbances due to arrhythmia proved to be
      minimal in three patients (standard deviation, <1.2%). CONCLUSION: Fast and
      accurate cardiac T1 mapping is feasible within a single-shot IR experiment.

PMID- 25393946
TI  - Shear-wave elastography for the estimation of liver fibrosis in chronic liver
      disease: determining accuracy and ideal site for measurement.
AB  - PURPOSE: To evaluate the accuracy of shear-wave elastography (SWE) for staging
      liver fibrosis in patients with diffuse liver disease (including patients with
      hepatitis C virus [HCV]) and to determine the relative accuracy of SWE
      measurements obtained from different hepatic acquisition sites for staging liver
      fibrosis. MATERIALS AND METHODS: The institutional review board approved this
      single-institution prospective study, which was performed between January 2010
      and March 2013 in 136 consecutive patients who underwent SWE before their
      scheduled liver biopsy (age range, 18-76 years; mean age, 49 years; 70 men, 66
      women). Informed consent was obtained from all patients. SWE measurements were
      obtained at four sites in the liver. Biopsy specimens were reviewed in a blinded
      manner by a pathologist using METAVIR criteria. SWE measurements and biopsy
      results were compared by using the Spearman correlation and receiver operating
      characteristic (ROC) curve analysis. RESULTS: SWE values obtained at the upper
      right lobe showed the highest correlation with estimation of fibrosis (r = 0.41,
      P < .001). Inflammation and steatosis did not show any correlation with SWE
      values except for values from the left lobe, which showed correlation with
      steatosis (r = 0.24, P = .004). The area under the ROC curve (AUC) in the
      differentiation of stage F2 fibrosis or greater, stage F3 fibrosis or greater,
      and stage F4 fibrosis was 0.77 (95% confidence interval [CI]: 0.68, 0.86), 0.82
      (95% CI: 0.75, 0.91), and 0.82 (95% CI: 0.70, 0.95), respectively, for all
      subjects who underwent liver biopsy. The corresponding AUCs for the subset of
      patients with HCV were 0.80 (95% CI: 0.67, 0.92), 0.82 (95% CI: 0.70, 0.95), and
      0.89 (95% CI: 0.73, 1.00). The adjusted AUCs for differentiating stage F2 or
      greater fibrosis in patients with chronic liver disease and those with HCV were
      0.84 and 0.87, respectively. CONCLUSION: SWE estimates of liver stiffness
      obtained from the right upper lobe showed the best correlation with liver
      fibrosis severity and can potentially be used as a noninvasive test to
      differentiate intermediate degrees of liver fibrosis in patients with liver
      disease.

PMID- 25393948
TI  - Airport surveys at travel destinations--underutilized opportunities in travel
      medicine research?
AB  - BACKGROUND: Research in destination airports, especially in resource-poor areas,
      allows unique immediate access to travelers at the conclusion of their trip.
      Response rates are high and the recall gap small. Trip-related health matters can
      be elicited relatively easily. An insight into travelers' decision-making
      processes on location would fill large gaps in our knowledge regarding travel
      health advice provision; yet, this approach is still much underutilized. METHODS:
      Using PubMed, ScienceDirect, Google Scholar, and ProQuest, a review of the
      literature on airport surveys was conducted to determine where they were used,
      their response rates and purpose, and location-relevant methodological
      information. RESULTS: The lack of methodological guidelines in the reviewed
      literature resulted in recommendations for planning and conducting an airport
      survey at a destination airport. CONCLUSIONS: Millions of travelers in airports
      around the world represent an underutilized sample of potential study
      participants for topics that cannot be studied adequately in other settings.
      Benefiting from close cooperation between travel health professionals and airport
      authorities, researchers can expect not only large-scale convenience samples for
      surveys, but also opportunities to explore exciting and creative research topics
      to broaden our understanding of travel medicine and health.

PMID- 25393949
TI  - Borrelidin B: isolation, biological activity, and implications for nitrile
      biosynthesis.
AB  - Borrelidin (1) is a nitrile-containing bacterially derived polyketide that is a
      potent inhibitor of bacterial and eukaryotic threonyl-tRNA synthetases. We now
      report the discovery of borrelidin B (2), a tetrahydro-borrelidin derivative
      containing an aminomethyl group in place of the nitrile functionality in
      borrelidin. The discovery of this new metabolite has implications for both the
      biosynthesis of the nitrile group and the bioactivity of the borrelidin compound
      class. Screening in the SToPS assay for tRNA synthetase inhibition revealed that
      the nitrile moiety is essential for activity, while profiling using our in-house
      image-based cytological profiling assay demonstrated that 2 retains biological
      activity by causing a mitotic stall, even in the absence of the nitrile motif. 

PMID- 25393950
TI  - Three-dimensional frameworks based on dodecanuclear Dy-hydroxo wheel cluster with
      slow relaxation of magnetization.
AB  - Two new heterometallic coordination polymers, [Na4Ln12(stp)8(OH)16(H2O)12].10H2O
      [Ln = Dy (1) and Ho (2)], have been prepared from monosodium 2-sulfoterephthalate
      (NaH2stp), dysprosium acetate, or holmium acetate. They are isostructural,
      possessing a [Ln12(MU3-OH)16](20+) wheel-cluster core based on four vertex
      sharing cubane-like [Ln4(MU3-OH)4](8+) units. The Ln12 cores are linked by stp
      ligands into a three-dimensional (3D) architecture. Magnetic studies indicate
      that complex 1 exhibits slow relaxation of magnetization, and it can be regarded
      as the first 3D coordination assembly of a Dy12 cluster single-molecule magnet. 

PMID- 25393951
TI  - Ecosystem services and opportunity costs shift spatial priorities for conserving
      forest biodiversity.
AB  - Inclusion of spatially explicit information on ecosystem services in conservation
      planning is a fairly new practice. This study analyses how the incorporation of
      ecosystem services as conservation features can affect conservation of forest
      biodiversity and how different opportunity cost constraints can change spatial
      priorities for conservation. We created spatially explicit cost-effective
      conservation scenarios for 59 forest biodiversity features and five ecosystem
      services in the county of Telemark (Norway) with the help of the heuristic
      optimisation planning software, Marxan with Zones. We combined a mix of
      conservation instruments where forestry is either completely (non-use zone) or
      partially restricted (partial use zone). Opportunity costs were measured in terms
      of foregone timber harvest, an important provisioning service in Telemark.
      Including a number of ecosystem services shifted priority conservation sites
      compared to a case where only biodiversity was considered, and increased the area
      of both the partial (+36.2%) and the non-use zone (+3.2%). Furthermore,
      opportunity costs increased (+6.6%), which suggests that ecosystem services may
      not be a side-benefit of biodiversity conservation in this area. Opportunity cost
      levels were systematically changed to analyse their effect on spatial
      conservation priorities. Conservation of biodiversity and ecosystem services
      trades off against timber harvest. Currently designated nature reserves and
      landscape protection areas achieve a very low proportion (9.1%) of the
      conservation targets we set in our scenario, which illustrates the high
      importance given to timber production at present. A trade-off curve indicated
      that large marginal increases in conservation target achievement are possible
      when the budget for conservation is increased. Forty percent of the maximum
      hypothetical opportunity costs would yield an average conservation target
      achievement of 79%. 

PMID- 25393952
TI  - Inactivation of human salivary glutathione transferase P1-1 by hypothiocyanite: a
      post-translational control system in search of a role.
AB  - Glutathione transferases (GSTs) are a superfamily of detoxifying enzymes over
      expressed in tumor tissues and tentatively proposed as biomarkers for localizing
      and monitoring injury of specific tissues. Only scarce and contradictory reports
      exist about the presence and the level of these enzymes in human saliva. This
      study shows that GSTP1-1 is the most abundant salivary GST isoenzyme, mainly
      coming from salivary glands. Surprisingly, its activity is completely obscured by
      the presence of a strong oxidizing agent in saliva that causes a fast and
      complete, but reversible, inactivation. Although salivary alpha-defensins are
      also able to inhibit the enzyme causing a peculiar half-site inactivation, a
      number of approaches (mass spectrometry, site directed mutagenesis,
      chromatographic and spectrophotometric data) indicated that hypothiocyanite is
      the main salivary inhibitor of GSTP1-1. Cys47 and Cys101, the most reactive
      sulfhydryls of GSTP1-1, are mainly involved in a redox interaction which leads to
      the formation of an intra-chain disulfide bridge. A reactivation procedure has
      been optimized and used to quantify GSTP1-1 in saliva of 30 healthy subjects with
      results of 42+/-4 mU/mg-protein. The present study represents a first indication
      that salivary GSTP1-1 may have a different and hitherto unknown function. In
      addition it fulfills the basis for future investigations finalized to check the
      salivary GSTP1-1 as a diagnostic biomarker for diseases. 

PMID- 25393954
TI  - Carbon nanoparticle-based ratiometric fluorescent sensor for detecting mercury
      ions in aqueous media and living cells.
AB  - A novel nanohybrid ratiometric fluorescence sensor is developed for selective
      detection of mercuric ions (Hg(2+)), and the application has been successfully
      demonstrated in HEPES buffer solution, lake water, and living cells. The sensor
      comprises water-soluble fluorescent carbon nanoparticles (CNPs) and Rhodamine B
      (RhB) and exhibits their corresponding dual emissions peaked at 437 and 575 nm,
      respectively, under a single excitation wavelength (350 nm). The
      photoluminescence of the CNPs in the nanohybrid system can be completely quenched
      by Hg(2+) through effective electron or energy transfer process due to synergetic
      strong electrostatic interaction and metal-ligand coordination between the
      surface functional group of CNPs and Hg(2+), while that of the RhB remains
      constant. This results in an obviously distinguishable fluorescence color
      variation (from violet to orange) of the nanohybrid solution. This novel sensor
      can effectively identify Hg(2+) from other metal ions with relatively low
      background interference even in a complex system such as lake water. The
      detection limit of this method is as low as 42 nM. Furthermore, the sensing
      technique is applicable to detect Hg(2+) in living cells. 

PMID- 25393955
TI  - Methods for the selection of platelet products for alloimmune-refractory
      patients.
AB  - The ability to efficiently and accurately diagnose the cause(s) of platelet (PLT)
      refractoriness is paramount in providing effective PLT products for transfusion.
      Recent advances in methods for detecting and identifying alloantibodies against
      human leukocyte antigens (HLAs) and human PLT antigens, combined with accurate
      molecular techniques for HLA typing, have provided a framework for the
      development of clinical algorithms to support such patients. Alloantibodies may
      be detected and/or identified by several methods, including complement-dependent
      cytotoxicity, enzyme-linked immunosorbent assays (ELISA), and microbead-based
      assays using Luminex or flow cytometry. The primary difference in these assays is
      the sensitivity of detection and the range of antibody specificities that may be
      reliably identified. Direct PLT cross-matching to identify compatible PLTs can be
      accomplished by several methods, including solid-phase red cell adherence,
      modified antigen capture ELISA, and flow cytometry. A survey of blood centers and
      laboratories providing transfusion support has identified the heterogeneity of
      testing options available, areas of concern and need for improvement, and common
      obstacles in providing appropriate and timely support to immune-refractory PLT
      patients. Depending on the testing methods and the pool of HLA-typed PLT donors
      available, there are numerous options for developing suitable algorithms to
      provide effective support to immune-refractory PLT patients. 

PMID- 25393953
TI  - Loss of dopamine D2 receptors increases parvalbumin-positive interneurons in the
      anterior cingulate cortex.
AB  - Disruption to dopamine homeostasis during brain development has been implicated
      in a variety of neuropsychiatric disorders, including depression and
      schizophrenia. Inappropriate expression or activity of GABAergic interneurons are
      common features of many of these disorders. We discovered a persistent
      upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate
      cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron
      markers were unaffected. Interneuron distribution and number were not altered in
      the striatum or in the dopamine-poor somatosensory cortex. The changes were
      already present by postnatal day 14, indicating a developmental etiology. D2eGFP
      BAC transgenic mice demonstrated the presence of D2 receptor expression within a
      subset of parvalbumin-expressing cortical interneurons, suggesting the
      possibility of a direct cellular mechanism through which D2 receptor stimulation
      regulates interneuron differentiation or survival. D2 receptor knockout mice also
      exhibited decreased depressive-like behavior compared with wild-type controls in
      the tail suspension test. These data indicate that dopamine signaling modulates
      interneuron number and emotional behavior and that developmental D2 receptor loss
      or blockade could reveal a potential mechanism for the prodromal basis of
      neuropsychiatric disorders. 

PMID- 25393956
TI  - Free radical scavengers improve liver function but not morphological changes
      induced by reperfusion injury.
AB  - OBJECTIVE: Reperfusion injury (RI) is associated with high generation of reactive
      oxygen species (ROS), but the extent of involvement of these agents in the injury
      remains controversial. The present study aimed to examine the effectiveness of
      ROS scavengers against hepatic reperfusion injury in the rat. METHODS: The RI was
      induced in the liver using an isolated slow-flow, reflow perfused rat liver in
      both anterograde and retrograde perfusion. The effects of gentisic acid, N-acetyl
      cysteine, and trolox C on the superoxide production, liver function, and
      morphological changes were examined using different biochemical and histological
      assays. RESULTS: The hepatic RI caused a significant (p < 0.05) increase in
      superoxide production and enzyme releases and a decrease in bile flow in both
      directions. Histological changes induced by RI include apoptosis, necrosis, pale
      cytoplasm, cell vacuolation, and attenuation of cell cords. Although the
      production of superoxide in retrograde direction was significantly less than the
      anterograde, the extent of the injury in the retrograde was greater than the
      anterograde direction. Pretreatment of the livers with each of the test compounds
      significantly reduced the release of lactate dehydrogenase and aspartate
      aminotransferase and improved bile flow in the liver exposed to
      hypoxia/reperfusion. However, they failed to protect the liver against the
      structural alterations induced by RI. CONCLUSION: ROS scavengers can reduce
      superoxide-induced damage and improve the liver function, but they are not able
      to prevent the structural changes. It shows that ROS are not the sole causative
      mechanism of hepatic RI and other mechanisms and mediators may be involved.

PMID- 25393957
TI  - Effect of hydrophobic interactions on the folding mechanism of beta-hairpins.
AB  - Hydrophobic interactions are essential in stabilizing protein structures. How
      they affect the folding pathway and kinetics, however, is less clear. We used
      time-resolved infrared spectroscopy to study the dynamics of hydrophobic
      interactions of beta-hairpin variants of the sequence Trpzip2 (SWTWENGKWTWK-NH2)
      that is stabilized by two cross-strand Trp-Trp pairs. The hydrophobicity strength
      was varied by substituting the tryptophans pairwise by either tyrosines or
      valines. Relaxation dynamics were induced by a laser-excited temperature jump,
      which separately probed for the loss of the cross-strand beta-hairpin interaction
      and the rise of the disordered structure. All substitutions tested result in
      reduced thermal stability, lower transition temperatures, and faster dynamics
      compared to Trpzip2. However, the changes in folding dynamics depend on the amino
      acid substituted for Trp. The aromatic substitution of Tyr for Trp results in the
      same kinetics for the unfolding of sheet and growth of disorder, with similar
      activation energies, independent of the substitution position. Substitution of
      Trp with a solely hydrophobic Val results in even faster kinetics than
      substitution with Tyr but is additionally site-dependent. If the hairpin has a
      Val pair close to its termini, the rate constants for loss of sheet and gain of
      disorder are the same, but if the pair is close to the turn, the sheet and
      disorder components show different relaxation kinetics. The Trp -> Val
      substitutions reveal that hydrophobic interactions alone weakly stabilize the
      hairpin structure, but adding edge-to-face aromatic interaction strengthens it,
      and both modify the complex folding process. 

PMID- 25393958
TI  - Function-based mutation-resistant synthetic signaling device activated by HIV-1
      proteolysis.
AB  - The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) virus
      is a major problem since it evades the function of antibodies and chemical
      inhibitors. Here, we demonstrate a viral detection strategy based on synthetic
      biology principles to detect a specific viral function rather than a particular
      viral protein. The resistance caused by mutations can be circumvented since the
      mutations that cause the loss of function also incapacitate the virus. Many
      pathogens encode proteases that are essential for their replication and that have
      a defined substrate specificity. A genetically encoded sensor composed of a fused
      membrane anchor, viral protease target site, and an orthogonal transcriptional
      activator was engineered into a human cell line. The HIV-1 protease released the
      transcriptional activator from the membrane, thereby inducing transcription of
      the selected genes. The device was still strongly activated by clinically
      relevant protease mutants that are resistant to protease inhibitors. In the
      future, a similar principle could be applied to detect also other pathogens and
      functions. 

PMID- 25393960
TI  - Post-market safety warnings for drugs approved in Canada under the Notice of
      Compliance with conditions policy.
AB  - AIMS: Health Canada has developed a pathway to approve drugs that have limited
      efficacy and safety data, the Notice of Compliance with conditions (NOC/c)
      policy. Increased safety reporting is required for these drugs but there has not
      been any systematic review of their post-market safety. This study compares
      safety warnings for NOC/c drugs with drugs with a priority and a standard review.
      METHODS: A list of drugs approved between January 1 1998 and March 31 2013 was
      developed and serious safety warnings for these drugs were identified. Drugs were
      put into one of three groups based on the way that they were approved. Kaplan
      Meier curves were generated to examine the likelihood of NOC/c drugs receiving a
      serious safety warning compared with drugs with a priority and a standard review.
      The time spent in the review process for each of the groups was also measured.
      RESULTS: Compared with drugs with a priority review, NOC/c drugs were not more
      likely to receive a serious safety warning (P = 0.5940) but were more likely than
      drugs with a standard review (P = 0.0113). NOC/c drugs spent less time in the
      review process compared with drugs with a standard review. CONCLUSIONS: Possible
      reasons for the increase likelihood of a serious safety warning are the limited
      knowledge of the safety of NOC/c drugs when they are approved and the length of
      time that they spend in the review process. Health Canada should consider
      spending longer reviewing these drugs and monitor their post-market safety more
      closely.

PMID- 25393959
TI  - Inhibition of platelet activation and thrombus formation by adenosine and
      inosine: studies on their relative contribution and molecular modeling.
AB  - BACKGROUND: The inhibitory effect of adenosine on platelet aggregation is
      abrogated after the addition of adenosine-deaminase. Inosine is a naturally
      occurring nucleoside degraded from adenosine. OBJECTIVES: The mechanisms of
      antiplatelet action of adenosine and inosine in vitro and in vivo, and their
      differential biological effects by molecular modeling were investigated. RESULTS:
      Adenosine (0.5, 1 and 2 mmol/L) inhibited phosphatidylserine exposure from 52+/
      4% in the control group to 44+/-4 (p<0.05), 29+/-2 (p<0.01) and 20+/-3%
      (p<0.001). P-selectin expression in the presence of adenosine 0.5, 1 and 2 mmol/L
      was inhibited from 32+/-4 to 27+/-2 (p<0.05), 14+/-3 (p<0.01) and 9+/-3%
      (p<0.001), respectively. At the concentrations tested, only inosine to 4 mmol/L
      had effect on platelet P-selectin expression (p<0.05). Adenosine and inosine
      inhibited platelet aggregation and ATP release stimulated by ADP and collagen.
      Adenosine and inosine reduced collagen-induced platelet adhesion and aggregate
      formation under flow. At the same concentrations adenosine inhibited platelet
      aggregation, decreased the levels of sCD40L and increased intraplatelet cAMP. In
      addition, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent
      adenosine receptor A2A antagonist) attenuated the effect of adenosine on platelet
      aggregation induced by ADP and intraplatelet level of cAMP. Adenosine and inosine
      significantly inhibited thrombosis formation in vivo (62+/-2% occlusion at 60 min
      [n = 6, p<0.01] and 72+/-1.9% occlusion at 60 min, [n = 6, p<0.05], respectively)
      compared with the control (98+/-2% occlusion at 60 min, n = 6). A2A is the
      adenosine receptor present in platelets; it is known that inosine is not an A2A
      ligand. Docking of adenosine and inosine inside A2A showed that the main
      difference is the formation by adenosine of an additional hydrogen bond between
      the NH2 of the adenine group and the residues Asn253 in H6 and Glu169 in EL2 of
      the A2A receptor. CONCLUSION: Therefore, adenosine and inosine may represent
      novel agents lowering the risk of arterial thrombosis.

PMID- 25393961
TI  - Microstructural abnormality in left nucleus accumbens predicts dysfunctional
      beliefs in treatment-resistant obsessive-compulsive disorder.
AB  - BACKGROUND: The aim of this study was to determine whether dysfunctional beliefs
      might predict treatment-resistance and to examine the relationship between
      fractional anisotropy (FA) in diffusion tensor imaging (DTI) and cognitive biases
      for optimal treatment choice. MATERIAL/METHODS: We recruited 11 non-resistant
      obsessive-compulsive disorder (OCD) patients, 11 resistant OCD patients, and 11
      healthy subjects. RESULTS: OCD patients had higher Obsessive Beliefs
      Questionnaire (OBQ-87) subscale scores than subjects in non-resistant and
      resistant groups. A significant difference was found between non-resistant and
      resistant OCD patients in R-Scale and I-Scale. A significant decrease in FA was
      found in left dorsal frontal gyrus and left inferior parietal lobule in the non
      resistant group as compared to the control group. FA also decreased significantly
      in left anterior cingulate cortex, putamen, and nucleus accumbens in the
      resistant group as compared to the control group. There was a significant
      decrease in FA in nucleus accumbens in the resistant group as compared to the non
      resistant group. Reduced FA in left nucleus accumbens was negatively associated
      with OBQ-87 factor R and I and the total Yale-Brown Obsessive-Compulsive Scale (Y
      BOCS). CONCLUSIONS: Abnormalities in cortical-striatal white matter networks may
      contribute to the dysfunctional beliefs in patients with treatment-resistant OCD,
      and the left nucleus accumbens may be an important and promising target for the
      treatment of OCD.

PMID- 25393962
TI  - Accuracy of predicting genomic breeding values for carcass merit traits in Angus
      and Charolais beef cattle.
AB  - Accuracy of predicting genomic breeding values for carcass merit traits including
      hot carcass weight, longissimus muscle area (REA), carcass average backfat
      thickness (AFAT), lean meat yield (LMY) and carcass marbling score (CMAR) was
      evaluated based on 543 Angus and 400 Charolais steers genotyped on the Illumina
      BovineSNP50 Beadchip. For the genomic prediction within Angus, the average
      accuracy was 0.35 with a range from 0.32 (LMY) to 0.37 (CMAR) across different
      training/validation data-splitting strategies and statistical methods. The within
      breed genomic prediction for Charolais yielded an average accuracy of 0.36 with a
      range from 0.24 (REA) to 0.46 (AFAT). The across-breed prediction had the lowest
      accuracy, which was on average near zero. When the data from the two breeds were
      combined to predict the breeding values of either breed, the prediction accuracy
      averaged 0.35 for Angus with a range from 0.33 (REA) to 0.39 (CMAR) and averaged
      0.33 for Charolais with a range from 0.18 (REA) to 0.46 (AFAT). The prediction
      accuracy was slightly higher on average when the data were split by animal's
      birth year than when the data were split by sire family. These results
      demonstrate that the genetic relationship or relatedness of selection candidates
      with the training population has a great impact on the accuracy of predicting
      genomic breeding values under the density of the marker panel used in this study.

PMID- 25393963
TI  - Cilostazol does not improve peripheral arterial disease-linked oxidative stress.
AB  - AIM: Cilostazol is a drug widely used to treat peripheral arterial disease (PAD)
      in patients with advanced atherosclerosis. It is an inhibitor of platelet
      aggregation and causes arterial vasodilatation. It has been speculated that
      cilostazol might act to improve oxidative stress in these patients. METHODS: We
      analyzed 25 patients with demonstrated lower limb peripheral arterial disease to
      determine whether lipid peroxidation (LPO) or total antioxidant capacity (TAC)
      were modified after 6 months of cilostazol treatment (postintervention phase)
      with respect to the basal phase. RESULTS: Analysis of plasma samples determined
      that LPO levels decreased significantly over the postintervention phase (26+/-15
      vs. 11+/-7 pM, P=0.0003). However, when TAC levels were analyzed, no significant
      differences were observed (0.80+/-0.21 vs. 0.85+/-0.17 mM, P=0.42). Under basal
      conditions, LPO showed a positive correlation to treatment as judged by the ankle
      brachial index (r=0.800, P=0.002) as well as uric acid (r=0.508, P=0.03) and CRP
      (r=0.481, P=0.05) levels. In contrast, TAC negatively correlated with
      triglycerides (r=-0.879, P<0.0001) and microalbuminuria (r=-0.868, P<0.0001). In
      the postintervention phase, TAC negatively correlated with HbA1c (r=-0.570,
      P=0.02) and triglycerides (r=-0.864, P<0.0001). CONCLUSIONS: Our data indicate
      that cilostazol treatment does not improve oxidative stress in PAD patients after
      6 months of treatment. However, lipid peroxidation and total antioxidant capacity
      were affected by cilostrazol treatment, which could be related to altered
      reactive oxygen species production. Further research may be needed to determine
      the critical dose of cilostazol to clarify the protective role of this drug in
      PAD.

PMID- 25393964
TI  - Medical intervention in parent-reported infant gastro-oesophageal reflux: A
      population-based study.
AB  - AIM: To report the cumulative incidence, health-seeking behaviour and medical
      intervention of infants with gastro-oesophageal reflux (GOR) in the first year of
      life. METHODS: The HealthNuts study is a longitudinal, population-based study. At
      12 months of age, infants underwent skin prick testing to food allergens,
      including cows milk. Parents completed a questionnaire on GOR symptoms, food
      allergy and treatments. Factors associated with seeking health care for infants
      with GOR were modelled using logistic regression. RESULTS: Of 4674 infants,
      parents reported GOR in 1054 (23%; 95% confidence interval (CI) 21.4-23.8).
      Parents consulted a medical practitioner in 662 (64%) cases. Symptoms commenced
      in the first month in 411 (48%) and resolved within 6 months in 703 (75%)
      infants. Factors associated with doctor consultation for GOR were prematurity
      (adjusted odds ratio (aOR) 1.94; 95% CI 1.43-2.63) and family history of atopy
      (aOR 1.64; 95% CI 1.1-2.43). Eight per cent of infants (371/4674; 95% CI 7.2-8.7)
      received anti-reflux medication and 6% (296/4674; 95% CI 5.7-7.1) changed
      formula. Parents were more likely to seek treatment if they perceived their
      infant to be unsettled (aOR 2.55; 95% CI 1.26-5.17) and if the duration of GOR
      was prolonged (aOR 3.36 for symptoms >6 months; 95% CI 1.83-6.17). CONCLUSIONS:
      In the first year of life, approximately 14% of the population seek medical
      advice for GOR symptoms. The use of anti-reflux medication in the general
      community remains high, despite the absence of evidence that it is appropriate or
      effective for uncomplicated GOR.

PMID- 25393965
TI  - The Effect of Porous Medium Storage on Unstable Density-Driven Solute Transport.
AB  - Unstable density-driven groundwater flow and solute transport (i.e., free
      convection) leads to spatiotemporal variations in pressure. Specific storage (So
      ) indicates the capability of a confined aquifer to release or store groundwater
      associated with a pressure change. Although So is known to dampen pressure
      propagation, So has been implicitly assumed to have a negligible impact on the
      unstable free convective process in prior studies. This work explores the effect
      of So on both the classic onset criterion and the fingering process using
      numerical models. Results show that the classic onset criterion is applicable
      when So is smaller than 10(-1) m(-1) . Results also demonstrate that So does not
      play a significant role in the free convective fingering process unless it is
      greater than 10(-3) m(-1) . For most practical purposes in hydrogeology (large
      Rayleigh number and small So ), the implicit assumption of small or zero So is
      appropriate. 

PMID- 25393966
TI  - Modeling the tight focusing of beams in absorbing media with Monte Carlo
      simulations.
AB  - A severe drawback to the scalar Monte Carlo (MC) method is the difficulty of
      introducing diffraction when simulating light propagation. This hinders, for
      instance, the accurate modeling of beams focused through microscope objectives,
      where the diffraction patterns in the focal plane are of great importance in
      various applications. Here, we propose to overcome this issue by means of a
      direct extinction method. In the MC simulations, the photon paths' initial
      positions are sampled from probability distributions which are calculated with a
      modified angular spectrum of the plane waves technique. We restricted our study
      to the two-dimensional case, and investigated the feasibility of our approach for
      absorbing yet nonscattering materials. We simulated the focusing of collimated
      beams with uniform profiles through microscope objectives. Our results were
      compared with those yielded by independent simulations using the finite
      difference time-domain method. Very good agreement was achieved between the
      results of both methods, not only for the power distributions around the focal
      region including diffraction patterns, but also for the distribution of the
      energy flow (Poynting vector).

PMID- 25393967
TI  - Morphological phenotyping of mouse hearts using optical coherence tomography.
AB  - Transgenic mouse models have been instrumental in the elucidation of the
      molecular mechanisms behind many genetically based cardiovascular diseases such
      as Marfan syndrome (MFS). However, the characterization of their cardiac
      morphology has been hampered by the small size of the mouse heart. In this
      report, we adapted optical coherence tomography (OCT) for imaging fixed adult
      mouse hearts, and applied tools from computational anatomy to perform
      morphometric analyses. The hearts were first optically cleared and imaged from
      multiple perspectives. The acquired volumes were then corrected for refractive
      distortions, and registered and stitched together to form a single, high
      resolution OCT volume of the whole heart. From this volume, various structures
      such as the valves and myofibril bundles were visualized. The volumetric nature
      of our dataset also allowed parameters such as wall thickness, ventricular wall
      masses, and luminal volumes to be extracted. Finally, we applied the entire
      acquisition and processing pipeline in a preliminary study comparing the cardiac
      morphology of wild-type mice and a transgenic mouse model of MFS.

PMID- 25393968
TI  - Delayed luminescence to monitor programmed cell death induced by berberine on
      thyroid cancer cells.
AB  - Correlation between apoptosis and UVA-induced ultraweak photon emission delayed
      luminescence (DL) from tumor thyroid cell lines was investigated. In particular,
      the effects of berberine, an alkaloid that has been reported to have anticancer
      activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell
      lines, as representative of follicular and anaplastic thyroid human cancer,
      respectively, were chosen. The results show that berberine is able to arrest cell
      cycle and activate apoptotic pathway as shown in both cell lines by
      deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein
      overexpression. In parallel, changes in DL spectral components after berberine
      treatment support the hypothesis that DL from human cells originates mainly from
      mitochondria, since berberine acts especially at the mitochondrial level. The
      decrease of DL blue component for both cell lines could be related to the
      decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a
      hallmark of induced apoptosis. In contrast, the response in the red spectral
      range is different for the two cell lines and may be ascribed to a different iron
      homeostasis.

PMID- 25393969
TI  - Cardiac-induced localized thoracic motion detected by a fiber optic sensing
      scheme.
AB  - The cardiovascular health of the human population is a major concern for medical
      clinicians, with cardiovascular diseases responsible for 48% of all deaths
      worldwide, according to the World Health Organization. The development of new
      diagnostic tools that are practicable and economical to scrutinize the
      cardiovascular health of humans is a major driver for clinicians. We offer a new
      technique to obtain seismocardiographic signals up to 54 Hz covering both
      ballistocardiography (below 20 Hz) and audible heart sounds (20 Hz upward), using
      a system based on curvature sensors formed from fiber optic long period gratings.
      This system can visualize the real-time three-dimensional (3-D) mechanical motion
      of the heart by using the data from the sensing array in conjunction with a
      bespoke 3-D shape reconstruction algorithm. Visualization is demonstrated by
      adhering three to four sensors on the outside of the thorax and in close
      proximity to the apex of the heart; the sensing scheme revealed a complex motion
      of the heart wall next to the apex region of the heart. The detection scheme is
      low-cost, portable, easily operated and has the potential for ambulatory
      applications.

PMID- 25393970
TI  - Pulsed versus continuous wave low-level light therapy on osteoarticular signs and
      symptoms in limited scleroderma (CREST syndrome): a case report.
AB  - Limited cutaneous systemic sclerosis (lcSSc) was formerly known as CREST syndrome
      in reference to the associated clinical features: calcinosis, Raynaud's
      phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasias. The
      transforming growth factor beta has been identified as a major player in the
      pathogenic process, where low-level light therapy (LLLT) has been shown to
      modulate this cytokine superfamily. This case study was conducted to assess the
      efficacy of 940 nm using millisecond pulsing and continuous wave (CW) modes on
      osteoarticular signs and symptoms associated with lcSSc. The patient was treated
      two to three times a week for 13 weeks using a sequential pulsing mode on one
      elbow and a CW mode on the other. Efficacy assessments included inflammation,
      symptoms, pain, health scales, patient satisfaction, clinical global impression,
      and adverse effects monitoring. Considerable functional and morphologic
      improvements were observed after LLLT, with the best results seen with the
      pulsing mode. No adverse effects were noted. Pulsed LLLT represents a treatment
      alternative for osteoarticular signs and symptoms in limited scleroderma (CREST
      syndrome).

PMID- 25393971
TI  - Sp1 and the 'hallmarks of cancer'.
AB  - For many years, transcription factor Sp1 was viewed as a basal transcription
      factor and relegated to a role in the regulation of so-called housekeeping genes.
      Identification of Sp1's role in recruiting the general transcription machinery in
      the absence of a TATA box increased its importance in gene regulation,
      particularly in light of recent estimates that the majority of mammalian genes
      lack a TATA box. In this review, we briefly consider the history of Sp1, the
      founding member of the Sp family of transcription factors. We review the evidence
      suggesting that Sp1 is highly regulated by post-translational modifications that
      positively and negatively affect the activity of Sp1 on a wide array of genes.
      Sp1 is over-expressed in many cancers and is associated with poor prognosis.
      Targeting Sp1 in cancer treatment has been suggested; however, our review of the
      literature on the role of Sp1 in the regulation of genes that contribute to the
      'hallmarks of cancer' illustrates the extreme complexity of Sp1 functions. Sp1
      both activates and suppresses the expression of a number of essential oncogenes
      and tumor suppressors, as well as genes involved in essential cellular functions,
      including proliferation, differentiation, the DNA damage response, apoptosis,
      senescence and angiogenesis. Sp1 is also implicated in inflammation and genomic
      instability, as well as epigenetic silencing. Given the apparently opposing
      effects of Sp1, a more complete understanding of the function of Sp1 in cancer is
      required to validate its potential as a therapeutic target. 

PMID- 25393972
TI  - Stapedotomy in cochlear implant candidates with far advanced otosclerosis: a
      systematic review of the literature and meta-analysis.
AB  - OBJECTIVE: To evaluate the effect of stapedotomy in cochlear implant candidates
      with far-advanced otosclerosis (FAO). DESIGN: Systematic review of literature and
      meta-analysis. DATA SOURCES: PubMed, EMBASE, and Cochrane databases were searched
      for "stapedotomy" and "far-advanced otosclerosis" and their synonyms. The search
      was carried out on November 28, 2013; no language restrictions were applied.
      STUDY SELECTION: The initial search yielded 243 articles; a total of nine
      articles met our inclusion criteria (i.e., patients with FAO and aided speech
      recognition scores of <=50%) and were included in this review. In addition, a
      group of five patients (seven stapedotomies) of our own center was also included
      in this meta-analysis. DATA EXTRACTION: The methodologic quality of included
      studies was assessed by examining the study design, level of evidence, method of
      measurement, and adequacy of outcome reporting. The speech recognition scores
      before and after stapedotomy as well as the pure-tone average before and after
      stapedotomy were extracted. DATA SYNTHESIS: A random-effects model was fitted for
      calculating weighted means. The mean preoperative speech recognition score was
      11%; stapedotomy resulted in a mean postoperative speech recognition score of
      59%. The mean preoperative and postoperative pure-tone averages were 112 dB HL
      and 80 dB HL, respectively. Seventy-two percent of the patients no longer met the
      criterion for cochlear implantation (CI) (i.e., <50% speech recognition), and 35%
      of the patients reached a postoperative aided speech recognition of more than
      80%. CONCLUSION: Stapedotomy combined with hearing aid fitting results in a good
      outcome in a substantial amount of CI candidates with FAO. We feel that a
      stapedotomy should be attempted before considering CI in all patients with FAO.
      In patients with bilateral otosclerosis, a contralateral stapedotomy may offer
      patients the benefits of binaural processing. If bilateral stapedotomy yields an
      unsatisfactory outcome, the option for CI is still open.

PMID- 25393973
TI  - The clinical value of three-dimensional fluid-attenuated inversion recovery
      magnetic resonance imaging in patients with idiopathic sudden sensorineural
      hearing loss: a meta-analysis.
AB  - OBJECTIVE: To investigate the correlation between findings of three-dimensional
      fluid-attenuated inversion recovery magnetic resonance imaging (3D FLAIR MRI) and
      baseline as well as outcome variables of idiopathic sudden sensorineural hearing
      loss (ISSHL). DATA SOURCES: Publications of all languages listed in PubMed and
      EMBASE STUDY SELECTION: Studies of ISSHL patients without primary treatment and
      precontrast 3D FLAIR MRI scan was performed. DATA EXTRACTION: Demographical and
      clinical characteristics of patients were extracted and the quality of studies
      was evaluated using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Continuous and
      dichotomous data was synthesized in Inverse Variance and Mantel-Haenszel models,
      respectively. The aggregate results were estimated and displayed in forest plots.
      CONCLUSIONS: The presence of high signal (HS) in inner ear on 3D FLAIR MRI
      indicated more severe initial hearing loss, and the existence of HS in inner ear
      on 3D FLAIR MRI increased the incidence of vertigo by 2.88 times. Meta-analysis
      of the dichotomous data of hearing recovery rate showed the hazard of recovery in
      HS group was significantly less than the one in no signal (NS) group. The pooled
      hearing improvement in decibels also favored NS group, but statistically the
      difference was not significant.

PMID- 25393974
TI  - Otologic outcomes after blast injury: the Boston Marathon experience.
AB  - OBJECTIVE: Otologic trauma was the most common physical injury sustained after
      the April 15, 2013, Boston Marathon bombings. The goal of this study is to
      describe the resultant otologic morbidity and to report on early outcomes. STUDY
      DESIGN: Multi-institutional prospective cohort study. METHODS: Children and
      adults seen for otologic complaints related to the Boston Marathon bombings
      comprised the study population. Participants completed symptom assessments,
      quality-of-life questionnaires, and audiograms at initial and 6-month visits.
      Otologic evaluation and treatment, including tympanoplasty results, were
      reviewed. RESULTS: More than 100 patients from eight medical campuses have been
      evaluated for blast-related otologic injuries; 94 have enrolled. Only 7% had any
      otologic symptoms before the blasts. Ninety percent of hospitalized patients
      sustained tympanic membrane perforation. Proximity to blast (RR = 2.7, p < 0.01)
      and significant nonotologic injury (RR = 2.7, p < 0.01) were positive predictors
      of perforation. Spontaneous healing occurred in 38% of patients, and
      tympanoplasty success was 86%. After oral steroid therapy in eight patients,
      improvement in hearing at 2 and 4 kHz was seen, although changes did not reach
      statistical significance. Hearing loss, tinnitus, hyperacusis, and difficulty
      hearing in noise remain persistent and, in some cases, progressive complaints for
      patients. Otologic-specific quality of life was impaired in this population.
      CONCLUSION: Blast-related otologic injuries constitute a major source of ongoing
      morbidity after the Boston Marathon bombings. Continued follow-up and care of
      this patient population are warranted.

PMID- 25393975
TI  - Cotton-based diagnostic devices.
AB  - A good diagnostic procedure avoids wasting medical resources, is easy to use,
      resists contamination, and provides accurate information quickly to allow for
      rapid follow-up therapies. We developed a novel diagnostic procedure using a
      "cotton-based diagnostic device" capable of real-time detection, i.e., in vitro
      diagnostics (IVD), which avoids reagent contamination problems common to existing
      biomedical devices and achieves the abovementioned goals of economy, efficiency,
      ease of use, and speed. Our research reinforces the advantages of an easy-to-use,
      highly accurate diagnostic device created from an inexpensive and readily
      available U.S. FDA-approved material (i.e., cotton as flow channel and
      chromatography paper as reaction zone) that adopts a standard calibration curve
      method in a buffer system (i.e., nitrite, BSA, urobilinogen and uric acid assays)
      to accurately obtain semi-quantitative information and limit the cross
      contamination common to multiple-use tools. Our system, which specifically
      targets urinalysis diagnostics and employs a multiple biomarker approach,
      requires no electricity, no professional training, and is exceptionally portable
      for use in remote or home settings. This could be particularly useful in less
      industrialized areas. 

PMID- 25393976
TI  - Regulation of vesicular traffic at the T cell immune synapse: lessons from the
      primary cilium.
AB  - The signals that orchestrate the process of T cell activation are coordinated at
      the specialized interface that forms upon contact with an antigen presenting cell
      displaying a specific MHC-associated peptide ligand, known as the immune synapse.
      The central role of vesicular traffic in the assembly of the immune synapse has
      emerged only in recent years with the finding that sustained T-cell receptor
      (TCR) signaling involves delivery of TCR/CD3 complexes from an intracellular pool
      associated with recycling endosomes. A number of receptors as well as membrane
      associated signaling mediators have since been demonstrated to exploit this
      process to localize to the immune synapse. Here, we will review our current
      understanding of the mechanisms responsible for TCR recycling, with a focus on
      the intraflagellar transport system, a multimolecular complex that is responsible
      for the assembly and function of the primary cilium which we have recently
      implicated in polarized endosome recycling to the immune synapse. 

PMID- 25393977
TI  - Measuring health-related quality of life with the EQ-5D-Y instrument in children
      and adolescents with asthma.
AB  - AIM: Asthma is one of the most common chronic paediatric diseases worldwide and
      affects different dimensions of health-related quality of life. This study tested
      the feasibility and convergent validity of using the EQ-5D-Y instrument on
      children and adolescents with asthma. METHODS: A cross-sectional design was
      chosen, and children with asthma, aged from 8 to 16 years, were recruited from
      clinics in Stockholm, Sweden. To test convergent validity, the EQ-5D-Y instrument
      was combined with the Paediatric Quality of Life Questionnaire. RESULTS: The EQ
      5D-Y proved feasible as nearly 96% of the 94 respondents completed all items on
      the questionnaire. High and moderate correlations between the two instruments
      were found for the dimensions of 'doing usual activities' and 'activity
      limitations' and for 'having pain or discomfort' and 'symptoms'. The visual
      analogue scale of the ED-5D-Y correlated with the Paediatric Quality of Life
      Questionnaire total score and the self-rated health question. The dimensions on
      the EQ-5D-Y with most reported problems were 'usual activities', 'pain or
      discomfort' and 'worried, sad or unhappy'. CONCLUSION: The EQ-5D-Y instrument
      seemed to provide feasibility and convergent validity for measuring health
      related quality of life in children and adolescents with asthma.

PMID- 25393978
TI  - Principal component analysis of binding energies for single-point mutants of
      hT2R16 bound to an agonist correlate with experimental mutant cell response.
AB  - Directed evolution is a technique that enables the identification of mutants of a
      particular protein that carry a desired property by successive rounds of random
      mutagenesis, screening, and selection. This technique has many applications,
      including the development of G protein-coupled receptor-based biosensors and
      designer drugs for personalized medicine. Although effective, directed evolution
      is not without challenges and can greatly benefit from the development of
      computational techniques to predict the functional outcome of single-point amino
      acid substitutions. In this article, we describe a molecular dynamics-based
      approach to predict the effects of single amino acid substitutions on agonist
      binding (salicin) to a human bitter taste receptor (hT2R16). An experimentally
      determined functional map of single-point amino acid substitutions was used to
      validate the whole-protein molecular dynamics-based predictive functions.
      Molecular docking was used to construct a wild-type agonist-receptor complex,
      providing a starting structure for single-point substitution simulations. The
      effects of each single amino acid substitution in the functional response of the
      receptor to its agonist were estimated using three binding energy schemes with
      increasing inclusion of solvation effects. We show that molecular docking
      combined with molecular mechanics simulations of single-point mutants of the
      agonist-receptor complex accurately predicts the functional outcome of single
      amino acid substitutions in a human bitter taste receptor.

PMID- 25393979
TI  - Sequential Sonagashira and Larock indole synthesis reactions in a general
      strategy to prepare biologically active beta-carboline-containing alkaloids.
AB  - A general synthetic approach to beta-carboline-containing alkaloids was
      developed. Two consecutive palladium-mediated processes, a Sonagashira coupling
      and a Larock indole annulation reaction, are central to the method. The scope of
      the approach was investigated and found to be amenable for constructing a variety
      of biologically significant natural products and also for preparing substituted
      analogues for optimization and analysis of their biological properties. 

PMID- 25393980
TI  - Targeting IL-17 for pancreatic cancer prevention.

PMID- 25393981
TI  - Rethinking glioma treatment strategy.

PMID- 25393982
TI  - Galectin-3 leads to attenuation of apoptosis through Bax heterodimerization in
      human thyroid carcinoma cells.
AB  - Cancer cells survive escaping normal apoptosis and the blocks in apoptosis that
      keep cancer cells alive are promising candidates for targeted therapy. Galectin-3
      (Gal-3) is, a member of the lectin family, which is involved in cell growth,
      adhesion, proliferation and apoptosis. It remains elusive to understand the role
      of Gal-3 on apoptosis in thyroid carcinoma cells. Here, we report that Gal-3
      heterodimerizes Bax, mediated by the carbohydrate recognition domain (CRD) of Gal
      3, leading to anti-apoptotic characteristic. Gal-3/Bax interaction was suppressed
      by an antagonist of Gal-3, in which in turn cells became sensitive to apoptosis.
      The data presented here highlight that Gal-3 is involved in the anti-apoptosis of
      thyroid carcinoma cells. Thus, it suggests that targeting Gal-3 may lead to an
      improved therapeutic modality for thyroid cancer. 

PMID- 25393983
TI  - Micro- and macrosurgical techniques in the coverage of gingival recession using
      connective tissue graft: 2 years follow-up.
AB  - OBJECTIVE: The aim was to evaluate the clinical results of micro- and
      macrosurgical approaches in the coverage of gingival recession using connective
      tissue graft. MATERIAL AND METHODS: Twenty-one teeth in microsurgical group (test
      group) and 21 in macrosurgical group (control group) were treated using coronally
      positioned flap and subgingival connective tissue graft. Recession depth (RD),
      recession width (RW), root surface area (RSA), keratinized tissue width (KTW),
      probing depth, clinical attachment level, pain level during healing, and
      aesthetic results were evaluated for 24 months. RESULTS: RD, RW, and RSA were
      significantly lower at 1, 3, 6, and 24th months compared with baseline in both
      groups. RD was also significantly lower in the 1st month compared with 24th month
      in control group. RD and RSA at 24th month were significantly lower in
      microsurgical group. KTW significantly and similarly increased by 6th month in
      both groups. The pain levels in the donor and the recipient area decreased
      earlier in the microsurgical group, and aesthetic scores improved similarly in
      both groups. CONCLUSION: A microsurgical approach to root coverage with gingival
      recession is likely to preserve the clinical outcomes longer than macrosurgical
      approach, at least for 24 months. Healing appears to be faster using
      microsurgery, but aesthetic outcomes are similar. CLINICAL SIGNIFICANCE: This
      study evaluated the clinical results of microsurgical versus macrosurgical
      approaches to root coverage in cases of gingival recession. Based on the results
      of the study, pain levels in the donor and the recipient areas decreased earlier
      in the microsurgical group, and microsurgical approach resulted in significantly
      greater amount of root coverage at 24 months.

PMID- 25393984
TI  - Spatial distribution of bacterial communities and related biochemical properties
      in Luzhou-flavor liquor-fermented grains.
AB  - Grain fermenting with separate layers in a fermentation pit is the typical and
      experiential brewing technology for Chinese Luzhou-flavor liquor. However, it is
      still unclear to what extent the bacterial communities in the different layers of
      fermented grains (FG) effects the liquor's quality. In this study, the spatial
      distributions of bacterial communities in Luzhou-flavor liquor FG (top, middle,
      and bottom layers) from 2 distinctive factories (Jiannanchun and Fenggu) were
      investigated using culture-independent approaches (phospholipid fatty acid [PLFA]
      and polymerase chain reaction-denaturing gel electrophoresis [DGGE]). The
      relationship between bacterial community and biochemical properties was also
      assessed by Canonical correspondence analysis (CCA). No significant variation in
      moisture was observed in spatial samples, and the highest content of acidity and
      total ester was detected in the bottom layer (P < 0.05). A high level of ethanol
      was observed in the top and middle layers of Fenggu and Jiannanchun,
      respectively. Significant spatial distribution of the total PLFA was only shown
      in the 50-y-old pits (P < 0.05), and Gram negative bacteria was the prominent
      community. Bacterial 16S rDNA DGGE analysis revealed that the most abundant
      bacterial community was in the top layers of the FG both from Fenggu and
      Jiannanchun, with Lactobacillaceae accounting for 30% of the total DGGE bands and
      Lactobacillus acetotolerans was the dominant species. FG samples from the same
      pit had a highly similar bacterial community structure according to the
      hierarchal cluster tree. CCA suggested that the moisture, acidity, ethanol, and
      reducing sugar were the main factors affecting the distribution of L.
      acetotolerans. Our results will facilitate the knowledge about the spatial
      distribution of bacterial communities and the relationship with their living
      environment. 

PMID- 25393985
TI  - Curbing the epidemic on both sides of the Atlantic: a public health perspective.
AB  - HIV/AIDS continues to place a devastating toll on individuals, families and
      communities globally, and western industrialized countries are by no means
      exempt. Today, there are more than 1 million Americans and 100,000 Britons living
      with HIV, with a disproportionate burden of new and prevalent HIV infections
      borne by gay, bisexual and other men who have sex with men (MSM), racial/ethnic
      minorities, migrants and persons who use drugs. Epidemic concentration in urban
      areas, especially among: population sub-groups with high prevalence of risk
      behaviours; the socio-economically marginalized; or those with poor access to
      services, has been well documented. Recent increases in HIV incidence in the
      rural south US, and in MSM in both countries, reflect the dynamic and evolving
      nature of these epidemics. New national HIV prevention strategies in both
      countries have refocused attention on these domestic epidemics, prioritizing HIV
      testing scaling up, linkage to quality care and tackling long-standing health
      inequalities. There are also significant differences between the two countries -
      in part a reflection of the different health and social care systems; historical
      approaches to the funding and coordination of HIV prevention; and underlying
      patterns of health inequalities and their social and structural determinants. In
      addition, the social-political acceptability of using the sexual health frame to
      guide more holistic and integrated approaches to HIV prevention efforts remains a
      key difference. This presentation will compare and contrast HIV prevention
      responses in the US and UK over the past decade, identifying opportunities for
      enhancing the prevention response in these and other western industrialized
      countries in the 21st century. 

PMID- 25393986
TI  - Mechanisms underlying abnormalities of immune activation/coagulation in HIV
      infection.
AB  - Immune activation has been recognized as an important component of the
      pathogenesis of HIV infection since the first recognition of cases of AIDS in the
      early 1980s. Early in the AIDS epidemic, patients with HIV infection were noted
      to have elevated levels of serum immunoglobulins. CD38 expression on CD4+ T cells
      was shown to be an independent predictor of survival in 1999. The
      characterization of HIV-associated immune activation has become progressively
      sophisticated over the past several years. A consistent finding has been an
      association of poor clinical outcomes with markers of monocyte activation (IL-6
      and sCD14) and/or coagulation (D-dimer). These relationships have been shown to
      exist even in patients with plasma levels of HIV-1<50 copies/ml. While it is
      generally accepted that immune activation is related to HIV infection, there is
      less clarity regarding the pathways that lead to its expression. Among the forces
      reported to drive HIV-associated immune activation are innate and adaptive immune
      responses to HIV and related co-infections, homeostatic responses to CD4+ T cell
      depletion and translocation of microbial products across the intestinal wall.
      Recent work has identified a potential role for "defective" HIV-1 transcripts in
      driving immune activation. Studies examining the connections between the adaptive
      immune system and the coagulation cascade have led to the identification of PAR-1
      as a potential target for therapeutic intervention. Despite the successes
      experienced with cART, persistent immune activation in association with HIV
      infection remains a scientific and clinical problem that is yet to be solved. 

PMID- 25393987
TI  - 30 years of HIV: what have we learned?
AB  - I saw my first patient with severe immune deficiency in 1979 - a very low CD4
      count had been noted, but it was not until the first reports of an epidemic
      occurred in 1981 that the correct diagnosis was made. Subsequently, I have seen
      more than 15,000 patients with HIV-related immune deficiency, and my life has
      changed from helping terminally ill patients to die with dignity, in the early
      part of the epidemic to now providing drugs for an eminently treatable condition 
      a true miracle. I have a number of observations about the epidemic. Firstly, the
      courage with which many young people faced death and disablement was truly awe
      inspiring, and was the chief reason many of the earlier doctors treating these
      patients stayed in the field. Secondly, the role of activists was overwhelmingly
      positive forcing the epidemic to the top of the scientific and political agenda
      and keeping it there. It is also important that activism helped move an ethical
      agenda reducing the stigma of HIV infection and producing a liberal legal
      framework which allowed testing and treatment to be acceptable. The right of the
      world population to health as espoused by Jonathan Mann and others is also
      crucial. Thirdly, the combination of academic research, activist pressure (and
      scientific input) and mammon in the form of the pharmaceutical industry acting in
      concert produced knowledge which led to effective treatment in a breathtakingly
      short time. Particular tribute in my mind needs to be paid to the pharmaceutical
      companies in this regard. I believe that the scientific achievements of HIV
      research illustrate two things. First, science builds from one generation to the
      next and most (but not all of us) need to be humble about our personal
      contribution. Second, HIV treatment illustrates the primacy of well conducted
      randomized control trials. While cohort studies can add to our detailed knowledge
      of the epidemic, randomised controlled trials remain the cornerstone of most
      major advances. Fourthly, when human beings act in concert towards a common goal,
      amazing things can be achieved. In the late 1990s, the possibility of treatment
      for the millions of people with HIV in the developing world was seen as a distant
      dream. The present situation whilst not perfect is a tribute to individuals,
      volunteers, government (particularly American government under President Bush)
      and personal philanthropy (the Bill & Melinda Gates Foundation, and the Clinton
      Foundation) that have used scientific knowledge to benefit the global population.

PMID- 25393988
TI  - Towards an HIV cure.
AB  - Given the challenge of delivering complex, expensive and potentially harmful
      antiretroviral therapy (ART) on a global level, there is intense interest in the
      development of short-term, well-tolerated regimens that allow individuals to
      interrupt therapy indefinitely without experiencing a rebound in viremia. This so
      called "cure" or "remission" might be due to complete eradication of all
      replication-competent HIV during ART or durable host-mediated control of
      persistent virus in absence of ART. Recent heroic interventions such as
      hematopoietic stem cell transplant and very early initiation of antiretroviral
      therapy suggest that dramatic reductions in the reservoir size can be achieved,
      but that complete eradication will be difficult if not impossible to achieve.
      Most attempts to stimulate effective host-mediated control of HIV have failed. It
      is likely that for a true cure to be achieved, both approaches - reductions in
      the reservoir size and durable immune surveillance - will be needed, a state that
      is similar to that observed in "elite" controllers and post-treatment
      controllers. The implications for recent advances and setbacks in achieving HIV
      remission for future research priorities will be discussed. 

PMID- 25393989
TI  - Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in
      primary HIV infection.
AB  - INTRODUCTION: Despite normalization of total CD4 counts, ongoing immune
      dysfunction is noted amongst those on antiretroviral therapy (ART). Low CD4/CD8
      ratio is associated with a high risk of AIDS and non-AIDS events and may act as a
      marker of immune senescence [1]. This ratio is improved by ART although
      normalization is uncommon (~7%) [2]. The probability of normalization of CD4
      count is improved with immediate ART initiation in primary HIV infection (PHI)
      [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs.
      deferred ART at PHI. MATERIAL AND METHODS: Using data from the SPARTAC trial and
      the UK Register of HIV Seroconverters, we examined the effect of ART with time
      (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (>=1) adjusted for
      sex, risk group, ethnicity, enrolment from an African site and both CD4 count and
      age at ART initiation. We also examined that effect by dichotomizing HIV duration
      at ART initiation (ART started within six months of SC: early ART; ART
      initiated>six months after SC: deferred). We also considered time to CD4 count
      normalization (>=900 cells/mm(3)). RESULTS: In total, 353 initiated ART with
      median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early
      ART, 100 deferred ART. At one year after starting ART, 114/253 (45%) early ART
      had normalized CD4/8 ratio, compared with 11/99 (11%) in the deferred group,
      whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99
      (3%) in the deferred group. Individuals initiating within six months of PHI were
      significantly more likely to reach normal ratio than those initiating later (HR,
      95% CI 2.96, 1.75 - 5.01, p<0.001). The longer after SC ART was initiated, the
      reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI
      0.96 - 0.99 for each 30-day increase). CD4 count at ART initiation was also
      associated with normalization, as expected (HR 1.002, 95% CI 1.001 - 1.002,
      p<0.001). There was an association between normal CD4/CD8 ratio and being virally
      suppressed (<400 copies HIV RNA/ml) p<0.001. CD4 count normalization was also
      significantly more likely for those initiating early (HR 5.00, 95% CI 1.52 -
      16.41, p=0.008). CONCLUSIONS: The likelihood of achieving normalization of
      CD4/CD8 ratios was increased if ART was initiated within six months of PHI.
      Higher CD4/CD8 ratio may reflect a more "normal" immune phenotype conferring
      enhanced prognosis and predict post-treatment control.

PMID- 25393990
TI  - CD4+ cell count recovery in naive patients initiating cART, who achieved and
      maintained plasma HIV-RNA suppression.
AB  - INTRODUCTION: A key objective of combined antiretroviral therapy (cART) is to
      reach and maintain high CD4 cell counts to provide long-term protection against
      AIDS-defining opportunistic infections and malignancies, as well as other
      comorbidities. However, a high proportion of patients present late for care. Our
      objective was to assess CD4 cell count recovery up to seven years in naive
      patients initiating cART with at least three drugs in usual clinical care.
      METHODS: From the French Hospital Database on HIV, we selected naive individuals
      initiating cART from 2000 with at least two years of follow-up. Participants were
      further required to have achieved viral load suppression by six months after
      initiating cART and were censored in case of virological failure. We calculated
      the proportion of patients (Kaplan-Meier estimates) who achieved CD4 recovery to
      >500/mm(3) according to baseline CD4 cell count. RESULTS: A total of 15,025
      patients were analyzed with a median follow-up on ART of 65.5 months (IQR: 42.3
      96.0). At cART initiation, the median age was 38.6 years (IQR: 32.2-46.0), 9734
      (64.8%) were men, median CD4 cell count was 239 (IQR: 130-336) and 2668 (17.8%)
      had a prior AIDS event. RESULTS are presented in the Table 1. CONCLUSIONS: This
      study shows that CD4 cell counts continue to increase seven years after cART
      initiation, whatever the baseline CD4 cell count. Failing to achieve CD4 recovery
      with continuous viral load suppression is rare for naive patients initiating cART
      in routine clinical practice, but takes substantially longer in patients who
      initiate antiretroviral therapy at low CD4 cell counts.

PMID- 25393991
TI  - Determinants of IL-6 levels during HIV infection.
AB  - INTRODUCTION: Elevated IL-6 levels have been linked to increased risk of
      cardiovascular disease (CVD), cancer and death. Compared to the general
      population, treated HIV+ persons have 50-100% higher IL-6 levels, but few data on
      the determinants of IL-6 levels during HIV infection currently exist. MATERIAL
      AND METHODS: Participants in three international HIV trials (SMART, ESPRIT and
      SILCAAT) with IL-6 plasma levels measured at baseline were included (N=9864).
      Factors independently associated with log2-transformed IL-6 level were identified
      by multivariate linear regression; exponentiated estimates corresponding to fold
      differences (FDs) in IL-6 were calculated. Demographics (age, gender, race, BMI)
      and HIV-specific variables (nadir and entry CD4 counts, HIV-RNA, use of different
      ART regimens) were investigated in all three trials. In SMART (N=4498), smoking,
      comorbidities (CVD, diabetes, hepatitis B/C [HBV/HCV]), HDL-cholesterol, renal
      function (eGFR) and educational level were also assessed. RESULTS: Demographics
      associated with higher IL-6 were older age (FD [95% CI]: 1.09 [1.08-1.11] per 10
      yr) and higher BMI (1.02 [1.01-1.04] per 5 kg/m(2)), whereas black race was
      associated with reduced IL-6 (0.96 [0.93-0.99]). As for HIV variables, patients
      not receiving ART (1.36 [1.29-1.43]) and with higher HIV-RNA (1.24 [1.01-1.52]
      for >100,000 vs. <=500 copies/mL) had increased IL-6. Participants taking
      protease inhibitors (PI) had higher IL-6 (1.14[1.09-1.19]). Higher nadir CD4
      count (0.98 [0.97-0.99]/100 cells/uL) was related to lower IL-6. All evaluated
      comorbidities were related to higher IL-6; FDs in IL-6 were 1.08 [1.04-1.12] for
      smoking, 1.12 [1.02-1.24] for CVD, 1.07 [1.00-1.16] for diabetes and 1.12 [1.02
      1.24] for HBV (1.15 [1.02-1.30]) and 1.53 [1.45-1.62] for HCV. IL-6 increased
      with decreasing eGFR (0.98 [0.97-1.00]/10 mL/min) and HDL-cholesterol (0.98 [0.96
      0.99]/10 mg/mL). Lower education was related to higher IL-6 (1.09 [1.03-1.15] for
      high school vs. bachelor's degree). CONCLUSIONS: Higher IL-6 levels were
      associated with older age and non-black race, higher BMI and lower HDL
      cholesterol, ongoing HIV replication, low nadir CD4 counts, comorbidities and
      decreased renal function. This suggests that there are multiple causes of
      inflammation in treated HIV infection. A possible contribution from PI use was
      also observed. Contribution from inflammation to explain variation in clinical
      outcomes for these factors should be investigated.

PMID- 25393992
TI  - Orphans of the HIV epidemic: the challenges from toddlerhood to adolescence and
      beyond.
AB  - This presentation focuses on the challenges and practical issues faced each day
      by orphans of the HIV epidemic and the holistic care that can be provided, as
      they continue to grow from toddlerhood to adolescence and beyond. An HIV Research
      Trust Scholarship enabled me to spend quality time in a sub-Saharan African
      province worst hit by the HIV epidemic and to interact with local experts and
      learn from mutual clinical experience. It was an immensely useful exercise as the
      clinical spectra of the diseases are very similar to ours and they have ongoing
      active research programs very relevant to our setting. India is arguably home to
      the largest number of orphans of the HIV epidemic. The responsibility of caring
      for orphaned children overwhelms and pushes many extended families beyond their
      ability to cope. Many countries are experiencing large increases in the number of
      families headed by women and grandparents, or even young children. These
      households are often unable to meet basic needs, and so the number of children
      living on the streets is rising. Orphaned children are disadvantaged in many
      devastating ways. In addition to the trauma of witnessing the sickness and death
      of one or both parents and perhaps siblings, they lack the necessary parental
      guidance through crucial life-stages of identity formation and transition into
      adulthood. They are more likely to suffer damage to their cognitive and emotional
      development and be subjected to; exploitation in terms of labour, social
      exclusion, extreme economic uncertainty, physical and sexual abuse, illiteracy,
      malnutrition and illness. Education remains a distant dream. With stigma and
      discrimination, they lack legal protection, lose inheritance rights, access to
      essential services available to other community members and professional help
      from doctors, teachers and lawyers. The implications for these unfortunate
      children are extraordinarily grave but governments, international agencies, non
      governmental organizations, schools, other community groups and individuals can
      still alter the course of the crisis. The Committed Communities Development Trust
      (CCDT) is a voluntary secular Trust, reaching out to 300,000 people annually,
      focusing intensively on children affected and infected by HIV/AIDS, mainly
      orphans, child headed families, children living in street situations, brothels,
      institutions and children at risk of drug addiction, abuse and exploitation in
      Mumbai. We run several comprehensive HIV/AIDS programmes addressing issues of
      prevention, care, support, education, awareness, empowerment, training and
      research through strongly structured home-based care programs, community based
      programs and temporary residential shelters. The CCDT recognizes and understands
      the daunting challenges these children face and helps them overcome these as a
      team by providing comprehensive care and support, giving them an opportunity in
      life and enabling them to become productive citizens of tomorrow. 

PMID- 25393993
TI  - Efavirenz- but not nevirapine-based antiretroviral therapy decreases exposure to
      the levonorgestrel released from a sub-dermal contraceptive implant.
AB  - INTRODUCTION: Sub-dermal hormone implants, such as levonorgestrel (LNG), are a
      safe and desirable form of long-acting contraception, but their use among HIV
      positive women on antiretroviral therapy (ART) may be compromised given the
      potential for a cytochrome P450 3A-mediated drug-drug interaction. Our study
      aimed to characterize the pharmacokinetics of LNG released from a sub-dermal
      implant over six months in HIV-positive Ugandan women on nevirapine (NVP)- or
      efavirenz (EFV)-based ART. MATERIAL AND METHODS: This non-randomized, parallel
      group study compared LNG pharmacokinetics between HIV-positive Ugandan women not
      yet eligible for ART (control group, n=18) and those on stable NVP- (n=20) or EFV
      (n=20) based ART. The two-rod (75 mg/rod) LNG sub-dermal implant was inserted at
      study enrolment. LNG sampling was obtained pre-implant and at weeks 1, 4, 12 and
      24 post-insertion. LNG concentrations were analyzed using a validated LC-MS/MS
      method, with an assay calibration range of 50-1500 pg/mL. Safety monitoring,
      including a pregnancy test, was conducted at each study visit. RESULTS: At
      enrolment, participants had a mean age of 31 years; CD4+ cell counts were similar
      between the control, NVP and EFV groups (758, 645 and 568 cells/mm(3),
      respectively; p=0.09); all women in the NVP and EFV groups had an undetectable
      HIV-RNA. Women in the control group had a higher baseline body weight (73 kg)
      compared to those in the NVP (63 kg; p=0.03) or EFV groups (60 kg; p<0.01). By
      linear regression, weight was a significant predictor of LNG concentrations (1 kg
      increase in weight=5 pg/mL decrease in LNG, p=0.03). LNG concentrations are
      reported in the table. CONCLUSIONS: Over a 24-week period, LNG concentrations
      were 40-54% lower in women on EFV-based ART, despite their having a significantly
      lower body weight, compared to those not on ART. In women on NVP-based ART, LNG
      concentrations were 32-39% higher than those observed in the control group, a
      difference partially explained by body weight. These data confirm a significant
      drug interaction occurs between the LNG implant and EFV, adding to growing
      concern for reduced contraceptive efficacy with their combined use. In contrast,
      these data support use of the LNG implant with NVP-based ART.

PMID- 25393994
TI  - Darunavir pharmacokinetics throughout pregnancy and postpartum.
AB  - INTRODUCTION: Antiretroviral therapy is recommended during pregnancy for
      prevention of mother-to-child transmission (MTCT) of HIV. Physiological changes
      during pregnancy are known to affect the pharmacokinetics (PK) of protease
      inhibitors (PIs), leading to lower exposures in pregnant women. Here we examine
      the PK of DRV/r 800/100 mg once daily (OD) over the course of pregnancy and
      postpartum (PP). MATERIAL AND METHODS: In this prospective open-labelled study,
      HIV-positive pregnant women receiving darunavir/ritonavir as part of their
      routine maternity care were enrolled. DRV plasma trough concentrations [DRV] were
      determined in the first (T1) and/or second (T2) and/or third (T3) trimester and
      PP using a validated HPLC-MS/MS methodology (Lab21, Cambridge UK). Where possible
      paired maternal and cord blood samples were taken at delivery. RESULTS: To date
      20 women (12 black African, 8 Caucasian) have been enrolled. Median (range)
      baseline CD4 count was 338 cells/uL (108-715), and median baseline plasma viral
      load was 555 copies/mL (<40-8,188,943). All but 2 women were virally suppressed
      at time of delivery (114 and 176 copies/mL; 1 sub-therapeutic at T3) and median
      CD4 count was 410 cells/uL (92-947). There were 20 live births, all term
      deliveries and there were no cases of MTCT. [DRV] (geometric mean; 95% CI) was
      3790 ng/mL at T1 (n=1); 1288 ng/mL (663-1913) at T2 (n=9); 1086 ng/mL (745-1428)
      at T3 (n=18, 1 undetectable) and 2324 ng/mL (1369-3279) at PP (n=14, 1
      undetectable). There was no significant difference in [DRV] between T2 and PP
      (p=0.158); however, there was between T3 and PP (p=0.021). Nineteen of twenty
      (95%) and 16 of 20 (80%) women achieved [DRV] above the estimated MEC for WT (55
      ng/mL) and PI resistant HIV-1 (550 ng/mL) throughout pregnancy. Maternal and cord
      [DRV] were available for 10 mother-baby pairs. Mean maternal [DRV] at delivery
      was 2235 ng/mL (+/-1557 ng/mL), while mean cord [DRV] was 337 ng/mL (+/-217
      ng/mL). The median cord to maternal blood ratio (C/M) was 0.11 (0.06-0.49).
      CONCLUSIONS: In most cases examined, DRV/r 800/100 mg once daily was effective at
      achieving adequate therapeutic drug levels (>550 ng/ml) during pregnancy.
      However, reduced DRV plasma concentrations in the second/third trimesters
      highlights the need for TDM in this population and warrants further study of
      pregnancy-associated changes in DRV pharmacokinetics. The low C/M ratios reported
      here are consistent with previous reports [1] and suggest low transplacental
      transfer of DRV.

PMID- 25393995
TI  - Does pregnancy increase the risk of ART-induced hepatotoxicity among HIV-positive
      women?
AB  - INTRODUCTION: High rates of hepatotoxicity have been observed among HIV-positive
      pregnant women using antiretroviral therapy (ART). However, the extent to which
      pregnancy affects the risk of ART-induced hepatotoxicity is unclear since studies
      in this area have generated conflicting results. MATERIAL AND METHODS: Combined
      data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland
      National Study of HIV in Pregnancy and Childhood (NSHPC) were used. Alanine
      aminotransferase (ALT) data were assessed according to the Division of AIDS
      toxicity guidelines to identify factors associated with liver enzyme elevation
      (LEE) (grade 1-4). Women starting ART in 2000-11 aged 16-49 years were included
      irrespective of pregnancy status at ART start. Cox proportional hazards were used
      to assess the associations between fixed (ethnicity, exposure group, HBV/HCV co
      infection, prior ART use, and age, year, pregnancy status, viral load and CD4
      count at ART start) and time-dependent covariates (pregnancy status, age, year,
      CD4 count, viral load, duration on ART) and the risk of LEE. RESULTS: Of the 3426
      women included, one-quarter (25.0%, n=857) were pregnant during follow-up and
      14.4% (n=492) started ART during pregnancy. The rate of LEE was 15/100 person
      years (PY) during pregnancy and 6.1/100 PY outside pregnancy. The risk of LEE was
      increased during pregnancy (adjusted hazard ratio (aHR) 1.61 [1.26-2.06],
      p<0.001), including in secondary analysis excluding 493 women pregnant when
      starting ART. Other factors independently associated with LEE were lower CD4
      count (<250 cells/mm(3) vs. 251-350 cells/mm(3) aHR 1.25 [1.02-1.54], p=0.03),
      HBV/HCV co-infection (aHR 1.94 [1.58-2.39], p<0.001), HIV acquired via injecting
      drug use (aHR 1.61 [1.15-2.24], p=0.01 vs. heterosexually) and calendar year (aHR
      1.05 [1.02-1.08], p<0.001 per one year increase). Three ART drugs were associated
      with increased risk of LEE (efavirenz aHR 1.27 [1.06-1.50], p-value 0.008;
      maraviroc 4.19 [1.34-13.1], p=0.01; and nevirapine 1.59 [1.30-1.95], p-value
      <0.001). Use of zidovudine was associated with decreased risk of LEE (aHR 0.74
      [0.63-0.87], p<0.001) as was increasing time on an NNRTI-based regimen (aHR 0.91
      [0.86-0.96], p<0.001 per additional year). CONCLUSIONS: Pregnant women were at
      increased risk of LEE, highlighting the importance of close monitoring of
      toxicity biomarkers during pregnancy.

PMID- 25393996
TI  - From guidelines to action: implementation opportunities and realities.
AB  - The past decade has seen notable progress in confronting the HIV epidemic. By the
      end of 2013, almost 13 million persons living with HIV had access to
      antiretroviral therapy (ART) in low- and middle-income countries (LMIC). In
      addition, progress has also been achieved in terms of HIV prevention with 26 LMIC
      achieving a 50% decrease in number of new infections including 15 countries in
      sub-Saharan Africa. New research findings also offer new efficacious prevention
      interventions that offer new opportunities for further mitigation of new HIV
      infections. Such progress has inspired ambitious pronouncements such as achieving
      "The End of AIDS" or "An AIDS Free Generation." This progress has also motivated
      the development of new guidelines aimed to achieving these goals. Implementation
      of guideline recommendations, however, requires translation of these guidelines
      into actionable steps and then their successful delivery within established
      health services. The opportunities offered by new guidelines frequently meet the
      realities of the frailties of the health system. Achieving current ambitious
      global targets must confront the specific deficits in the health system that
      inhibit access and acceptability of programmes as well as hinder achievement of
      high quality or desired coverage. 

PMID- 25393997
TI  - Choice of initial therapy.
AB  - Current international and national treatment guidelines such as EACS, BHIVA, DHHS
      or IAS update regularly recommendations on the choice of initial combination
      antiretroviral treatment (cART) regimens. Preferred cART regimens include a
      backbone with two nucleoside (nucleotide) reverse transcriptase inhibitors
      combined either with one non-nucleoside reverse transcriptase inhibitor or one
      ritonavir boosted protease inhibitor or more recently one integrase inhibitor.
      Response rates according to viral load measurements increased in recent years, in
      particular due to better tolerability. The choice of initial therapy is flexible
      and influenced by several factors such as height of viral load, genotypic
      resistance testing, CD4 cell count, co-morbidities, interactions, potential
      adverse events, (potential for) pregnancy, convenience, adherence, costs as well
      as physician's and patient's preferences. Diverse highly potent initial cART
      regimens exist. Following the many possibilities, the choice of a regimen is
      based on a mixture of evidence-informed data and individualized concepts, some of
      the latter only partly supported by strong evidence. For example, different
      perceptions and personal experiences exist about boosted protease inhibitors
      compared to non-nucleoside reverse transcriptase inhibitors or integrase
      inhibitors and vice versa which may influence the initial choice. This lecture
      will discuss choices of initial cART in view of international guidelines and the
      evidence for individualization of initial HIV therapy. 

PMID- 25393998
TI  - Managing first-line failure.
AB  - WHO standard of care for failure of a first regimen, usually 2N(t)RTI's and an
      NNRTI, consists of a ritonavir-boosted protease inhibitor with a change in
      N(t)RTI's. Until recently, there was no evidence to support these recommendations
      which were based on expert opinion. Two large randomized clinical trials, SECOND
      LINE and EARNEST both showed excellent response rates (>80%) for the WHO standard
      of care and indicated that a novel regimen of a boosted protease inhibitor with
      an integrase inhibitor had equal efficacy with no difference in toxicity. In
      EARNEST, a third arm consisting of induction with the combined protease and
      integrase inhibitor followed by protease inhibitor monotherapy maintenance was
      inferior and led to substantial (20%) protease inhibitor resistance. These
      studies confirm the validity of the current recommendations of WHO and point to a
      novel public health approach of using two new classes for second line when
      standard first-line therapy has failed, which avoids resistance genotyping.
      Notwithstanding, adherence must be stressed in those failing first-line
      treatments. Protease inhibitor monotherapy is not suitable for a public health
      approach in low- and middle-income countries. 

PMID- 25393999
TI  - Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in
      treatment-naive HIV-1-positive individuals: 96 week results from FLAMINGO.
AB  - INTRODUCTION: Dolutegravir (DTG) 50 mg once daily was superior to
      darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily through Week 48, with 90%
      vs. 83% of participants achieving HIV RNA 50 c/mL (p=0.025) [1]. We present data
      through Week 96. MATERIAL AND METHODS: FLAMINGO is a multicentre, randomized,
      open-label, Phase IIIb non-inferiority study, in which HIV-1-positive ART-naive
      adults with HIV-1 RNA>=1000 c/mL and no evidence of viral resistance were
      randomized 1:1 to receive DTG or DRV/r, with investigator-selected backbone NRTIs
      (TDF/FTC or ABC/3TC). Participants were stratified by screening HIV-1 RNA (<=100K
      c/mL) and NRTI backbone. RESULTS: A total of 484 adults were randomized and
      treated; 25% had baseline HIV RNA 100K c/mL. At Week 96, the proportion of
      participants with HIV RNA 50 c/mL was 80% in the DTG arm vs. 68% in the DRV/r arm
      (adjusted difference 12.4%; 95% CI 4.7, 20.2%; p=0.002). Secondary analyses
      supported primary results: per-protocol [(DTG 83% vs. DRV/r 70%), 95% CI 12.9
      (5.3, 20.6)] and treatment-related discontinuation = failure [(98% vs. 95%), 95%
      CI 3.2 (-0.3, 6.7)]. Overall virologic non-response (DTG 8%; DRV/r 12%) and non
      response due to other reasons (DTG 12%; DRV/r 21%) occurred less frequently on
      DTG. As at Week 48, the difference between arms was most pronounced in
      participants with high baseline viral load (82% vs. 52% response through Week 96)
      and in the TDF/FTC stratum (79% vs. 64%); consistent responses were seen in the
      ABC/3TC stratum (82% vs. 75%). Six participants (DTG 2, none post-Week 48; DRV/r
      4, two post-Week 48) experienced protocol-defined virologic failure (PDVF;
      confirmed viral load 200 c/mL on or after Week 24); none had treatment-emergent
      resistance to study drugs. Most frequent drug-related adverse events (AEs) were
      diarrhoea, nausea and headache, with diarrhoea significantly more common on DRV/r
      (24%) than DTG (10%). Significantly more participants had Grade 2 fasting LDL
      toxicities on DRV/r (22%) vs. DTG (7%), p<0.001; mean changes in creatinine for
      DTG (~0.18 mg/dL) observed at Week 2 were stable through Week 96. CONCLUSIONS:
      Once-daily DTG was superior to once-daily DRV/r in treatment-naive HIV-1-positive
      individuals, with no evidence of emergent resistance to DTG in virologic failure
      and relatively similar safety profiles for DTG and DRV/r through 96 Weeks.

PMID- 25394000
TI  - More virological failure with lamivudine than emtricitabine in efavirenz and
      nevirapine regimens in the Dutch nationwide HIV Cohort.
AB  - INTRODUCTION: Lamivudine (3TC) and emtricitabine (FTC) are considered
      interchangeable by HIV-1 guidelines in first-line tenofovir/efavirenz (TDF/EFV)
      and TDF/nevirapine (NVP) combination antiretroviral therapy (cART). Data from
      trials on equivalence of 3TC and FTC are inconsistent. We examined the
      effectiveness of 3TC and FTC in the national HIV cohort in the Netherlands.
      MATERIAL AND METHODS: Observational cohort study on cART naive HIV-1 patients.
      Therapy was initiated as 3TC or FTC with TDF/EFV or TDF/NVP between 2002 and
      2012. Patients with baseline resistance or prior cART experience were excluded.
      Main outcomes were Week 48 virological failure (VF) by on treatment analysis,
      time to HIV-RNA <400 copies/mL within 48 weeks and VF within 240 weeks after at
      least one HIV-RNA <400 copies/mL. Acquired resistance to reverse transcriptase
      was evaluated. Analyses were done by logistic regression and Cox proportional
      hazard models. Propensity score adjusted models and intention to treat
      evaluations were included as sensitivity analysis. RESULTS: A total of 4836
      patients initiated 3TC/TDF/EFV (n=546), FTC/TDF/EFV (n=3391), 3TC/TDF/NVP (n=207)
      or FTC/TDF/NVP (n=692). Ninety-six patients were excluded for baseline resistance
      or prior cART experience. By Week 48, VF proportions were higher for 3TC/TDF/EFV
      (10.8%) compared to FTC/TDF/EFV (3.6%) and for 3TC/TDF/NVP (27.0%) compared to
      FTC/TDF/NVP (11.0%). The multivariable adjusted odds ratio (OR) on VF was 1.78
      (95% CI 1.11-2.84; p=0.016) with 3TC/TDF/EFV compared to FTC/TDF/EFV and 2.09
      (95% CI 1.25-3.52; p=0.005) with 3TC/TDF/NVP compared to FTC/TDF/NVP. Propensity
      score adjusted models and intention to treat analyses showed comparable results.
      The time to virological suppression within 48 weeks was not influenced by using
      3TC or FTC in cART. If HIV-RNA <400 copies/mL was achieved on initial cART first,
      no differences in VF within 240 weeks were observed between 3TC and FTC with
      TDF/EFV (p=0.090) or TDF/NVP (P=0.255). Patients failing 3TC-containing cART had
      higher median HIV-RNA at VF compared to FTC containing cART (p<0.001) and 89.8%
      had acquired resistance on 3TC compared to 81.2% on FTC. CONCLUSIONS: Including
      FTC in cART is associated with better virological responses compared to 3TC. As
      cost constraints may call for the use of generic 3TC, a well-powered randomized
      trial to confirm the presumed equivalence of 3TC and FTC is needed.

PMID- 25394001
TI  - Rational allocation of resources available for healthcare: understanding cost
      effectiveness analyst.
AB  - Health systems around the world are grappling with the difficult issue of how to
      allocate scare healthcare resources. Within Europe many different approaches to
      healthcare resource allocation exist, but it is clear that the formal techniques
      of cost-effectiveness analysis are becoming increasingly important. This
      presentation will first address the fundamental economic principles of scarcity
      and opportunity cost, before looking at how different European systems are
      attempting to address the economic challenge of providing healthcare for their
      population from a limited budget. The presentation will go on to consider general
      issues in health economic evaluation that are likely important for clinical
      community focused on HIV treatment: appropriate comparator treatments for
      defining opportunity cost, patient heterogeneity and the potential for
      personalized/stratified medicine to control costs and target treatment
      appropriately. 

PMID- 25394002
TI  - The challenge: streamlining HIV treatment and care while improving outcomes.
AB  - ART coverage among HIV-positive population varies, depending on the countries,
      between 10% (e.g. Indonesia) and 65% (Botswana). Death rates and new HIV
      infections have been linked to ART coverage. Therefore, streamlining tasks and
      roles to expand treatment and care and to provide quality and equitable health is
      an ongoing concern globally. One concept that has been applied to improve the
      delivery of HIV services is that of task shifting. Defined as the systematic
      delegation of tasks from doctors to cadre with less training such as nurses or
      lay workers, task shifting has been used as an effective strategy to address the
      current healthcare worker shortage in many African countries. A body of
      literature supports the use of task shifting as a successful approach in
      delivering healthcare services including HIV testing, counselling and ART
      treatment. In addition, in a time of economic burden and scare resources, task
      shifting may also help to relieve the situation. This concern is highlighted in
      recommendation of WHO to strengthen and expand human capacity among healthcare
      workers. The major issues that are raised are: How can task shifting be
      implemented in a way that is sustainable? How can clinical care services be
      organized to maximize the potential of the task-shifting approach while ensuring
      safety, efficiency and effectiveness? What preconditions must be met, what are
      the country-specific factors that will guide decision-making in the
      implementation of task shifting? In addition, task shifting should be implemented
      alongside other efforts to increase the numbers of skilled health workers.
      Quality assurances mechanisms should provide the necessary checks balances to
      protect both service users and health workers. 

PMID- 25394003
TI  - Models of care and delivery.
AB  - Marked regional differences in HIV-related clinical outcomes exist across Europe.
      Models of outpatient HIV care, including HIV testing, linkage and retention for
      positive persons, also differ across the continent, including examples of sub
      optimal care. Even in settings with reasonably good outcomes, existing models are
      scrutinized for simplification and/or reduced cost. Outpatient HIV care models
      across Europe may be centralized to specialized clinics only, primarily handled
      by general practitioners (GP), or a mixture of the two, depending on the setting.
      Key factors explaining this diversity include differences in health policy,
      health insurance structures, case load and the prevalence of HIV-related
      morbidity. In clinical stable populations, the current trend is to gradually
      extend intervals between HIV-specific visits in a shared care model with GPs. A
      similar shared-model approach with community clinics for injecting drug-dependent
      persons is also being implemented. Shared care models require oversight to ensure
      that primary responsibility is defined for the persons overall health situation,
      for screening of co-morbidities, defining indication to treat comorbidities,
      prescription of non-HIV medicines, etc. Intelligent bioinformatics platforms
      (i.e. generation of alerts if course of care deviates from a prior defined
      normality) are being developed to assist in providing this oversight and to
      provide measure of quality. Although consensus exists to assess basic quality
      indicators of care, a comprehensive set of harmonized indicators are urgently
      needed to define best practise standards via benchmarking. Such a tool will be
      central to guide ongoing discussions on restructuring of models, as quality of
      care should not be compromised in this process. 

PMID- 25394004
TI  - Integrated care pathways and task shifting.
AB  - Delivery of HIV care has evolved over the last 10 years, and nurse specialists
      are a driving force in developing new pathways to enhance patient care. Despite
      the continued rise in numbers of people living with HIV, the financial
      constraints on the NHS have unfortunately resulted in a reduction in service
      provision. Experienced nurses are integral to patient care management. They not
      only provide standardized care for stable patients, therefore increasing
      consultant capacity for the more complex medical patient, but have a degree of
      flexibility that allows newly diagnosed patients quick access to care and
      support. With a strong emphasis being placed on an integrated and collaborative
      multidisciplinary team approach, to ensure patients receive the same standard of
      care, Scotland's HIV centres follow an integrated care pathway. The nurse
      oversees the completion of this document and co-ordinates the pathway of care
      depending on the clinical need. Nurses develop and maintain necessary
      partnerships between primary care, specialist care, psychological services,
      social care and third sector support services. The nurse case load continues to
      expand and diversify. Stable patients may be maintained on therapy but are living
      with a stigmatized long-term chronic condition and rely on the nurse as a point
      of contact to access advice and support readily. The more chaotic and vulnerable
      clients with complex care needs require the nurse to co-ordinate their care,
      ensuring the appropriate agencies remain involved. Overseeing the transition of
      care to other units and tracing patients who are lost to follow up is also a
      necessity, as retention in care is paramount for the continued improvement in
      clinical outcomes. The contribution that specialist nurses make to the provision
      of HIV care is valuable and will continue to play a large role in the delivery of
      such care. 

PMID- 25394005
TI  - Enhancing patient self-management.
AB  - In the context of HIV as a chronic disease, care being delivered with more
      constrained budgets and being more complex as many patients are ageing, the need
      for disease self-management is increasingly recognized. Like in other chronic
      diseases, HIV care and treatment guidelines increasingly promote the enhancement
      of health management by patients, within a framework of closer collaboration with
      their healthcare providers. Therefore, patients progressively become key
      resources on which health systems should count for efficiency and improvement. Is
      this a principle or is this reality? We are aware that to count in healthcare,
      resources must be allocated the necessary support. How does the required support
      translate into patients' real lives? Do patient education programmes respond
      adequately to these needs? Are chronic care models really applicable in contexts
      where care is not yet sufficiently coordinated, especially with regards to people
      who are ageing with HIV and the multiple types of care they need? How far should
      a patient take responsibility for making best of healthcare resources? From the
      perspective of a person living and ageing with HIV, the role of patients in the
      management of their own health will be discussed. 

PMID- 25394006
TI  - Predicted savings to the UK National Health Service from switching to generic
      antiretrovirals, 2014-2018.
AB  - INTRODUCTION: In other disease areas, generic drugs are normally used after
      patent expiry. Patents on zidovudine, lamivudine, nevirapine and efavirenz have
      already expired. Patents will expire for abacavir in late 2014, lopinavir/r in
      2016, and tenofovir, darunavir and atazanavir in 2017. However, patents on single
      tablet regimens do not expire until after 2026. METHODS: The number of people
      taking each antiretroviral in the UK was estimated from 23,655 individuals in the
      UK CHIC cohort (2012 database). Costs of patented drugs were taken from the
      British National Formulary database, assuming a 30% discount. Costs of generic
      antiretrovirals were estimated using an 80% discount from patented prices, or
      actual costs where available. Two options were analysed: 1 - all patients use
      single-tablet regimens and patented versions of drugs; prices remain stable over
      time; 2 - all people switch from patented to generic drugs when available, after
      patent expiry (dates shown above). RESULTS: There were an estimated 67,000 people
      taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until
      2018 (in line with previous rises). The most widely used antiretrovirals in the
      CHIC cohort were tenofovir (TDF) (75%), emtricitabine (FTC) (69%), efavirenz
      (EFV) (39%), lamivudine (3TC) (23%), abacavir (ABC) (18%), darunavir (DRV) (21%)
      and atazanavir (ATV) (16%). The predicted annual UK cost of generic ABC/3TC/EFV
      (three generic tablets once daily) was L1018 per person-year. Costs of patented
      single-tablet regimens ranged from L5000 to L7500 per person-year. Assuming
      continued use of patented antiretrovirals in the UK, the predicted total national
      costs of antiretroviral treatment were predicted to rise from L425 million in
      2014 to L459 m in 2015, L495 m in 2016, L536 m in 2017 and L578 m in 2018. With a
      100% switch to generics, total predicted costs were L337 m in 2014, L364 m in
      2015, L382 m in 2016, L144 m in 2017 and L169 m in 2018. The total predicted
      saving over five years from a switch to generics was L1.1 billion. CONCLUSIONS:
      Systematic switching from patented to generic antiretrovirals could potentially
      save approximately L1.1 billion in the UK over the next five years, compared with
      continued use of patented versions: this money could be spent on urgently needed
      HIV prevention programmes. Similar savings are feasible for other European
      countries, given parallel patent expiry dates. More detailed economic evaluation
      is required to show when patented single-tablet regimens provide value for money,
      compared to bioequivalent generic versions of 3-4 pills once daily.

PMID- 25394007
TI  - Cost-effectiveness analysis of protease inhibitor monotherapy vs. ongoing triple
      therapy in the long-term management of HIV patients.
AB  - INTRODUCTION: Protease inhibitors might be sufficient to maintain complete
      virological suppression when used as monotherapy for HIV-1-positive patients who
      have achieved sustained virological suppression on combination antiretroviral
      therapy (ART). The present study estimated the cost-effectiveness of a strategy
      of switching the ART to protease inhibitor monotherapy (PIM) with prompt return
      to combination therapy in the event of viral load rebound compared to continuing
      the ongoing triple-therapy (OTT) in the long-term management of HIV-1-positive
      patients. MATERIALS AND METHODS: A within-trial cost-effectiveness analysis and
      modelling of lifetime cost-effectiveness was performed based on a randomized
      controlled trial of Protease Inhibitor monotherapy Versus Ongoing Triple-therapy
      (PIVOT). The setting was HIV outpatient care in the UK National Health Service,
      and the trial involved 587 patients, aged 18 years or more, who achieved
      sustained virological suppression and have a CD4+ cell count >100 cells/mm(3).
      Outcomes were NHS costs (2012 UK pounds sterling) and quality-adjusted life-years
      (QALY) with comparative results presented as incremental cost-effectiveness
      ratios (ICERs). RESULTS: Overall, PIM was cost-effective compared to OTT. PIM was
      cost-saving due to large savings in the ART drug costs while being no less
      effective in terms of QALYs in the within-trial analysis and only marginally less
      effective with modelling. In the base-case within-trial analysis, the incremental
      total cost per patient was -L6,424.11 (95% confidence interval:-L7,418.84 to 
      L5,429.38) and the incremental QALY was 0.0051 (95% confidence interval: -0.0479
      to 0.0582) making PIM dominant compared to OTT. Multiple sensitivity analyses
      were conducted to assess the importance of assumptions surrounding drug costs,
      missing data, trial protocol driven costs and mortality. In all sensitivity
      analyses, PIM was cost-saving and no marked difference in QALY was observed.
      Modelling of life time costs and QALYs showed significant cost-savings and
      marginally less effectiveness such that switching to PIM appeared cost-effective
      at accepted cost-effectiveness thresholds. CONCLUSIONS: The results suggest that
      PIM is a cost-effective treatment strategy compared to OTT for HIV-1-positive
      patients who have achieved sustained virological suppression.

PMID- 25394008
TI  - Hepatitis C, from screening to treatment, a revolution.
AB  - Initially associated with blood transfusions and hospital care, the hepatitis C
      virus (HCV) epidemic has since moved rapidly onwards to intravenous drug users,
      where it poses a major problem still today. Despite numerous harm reduction
      programs, such as needle exchange, opiate substitution and controlled shooting
      galleries, drug addiction remains the number one route of HCV transmission around
      the world. However, in HIV-positive patients, the HCV epidemic experienced a
      major shift in the mid-90s, with sexual transmission among particularly men who
      have sex with men (MSM) surfacing as a major route of HCV acquisition. Until
      recently, therapeutic options in HCV infection had been quite limited, based
      largely on the use of combined Peg-interferon and ribavirin, with disappointing
      results in HIV-positive patients. With the recent, exciting developments in HCV
      research, new targets on the virus replication cycle have been discovered. After
      the release in 2011 of the first direct antiviral agents inhibiting the NS3/4
      antiprotease, the development of drugs with newer mode of action, more efficient
      and with higher tolerance profiles has greatly accelerated. They may greatly
      change the course of treatment: once daily, highly active and easily-tolerated
      regimens, administered for a short period of time with HCV eradication in more
      than 90% of patients, independently of prior treatment, level of fibrosis and
      comorbidities such as HIV co-infection. This definitely has the potential to curb
      the HCV epidemic towards an HCV cure, provided that advocacy for broad-access to
      treatment is successful for those most in need. Their use in resource-constrained
      settings may also be the next political challenge for HCV. 

PMID- 25394009
TI  - Safety and efficacy of ombitasvir - 450/r and dasabuvir and ribavirin in HCV/HIV
      1 co-infected patients receiving atazanavir or raltegravir ART regimens.
AB  - OBJECTIVE: Whether concomitant HIV antiretroviral therapy (ART) affects the
      safety and efficacy of interferon-free HCV therapies or whether HCV treatment may
      negatively affect HIV control is unclear. We assessed the 3 direct-acting
      antiviral (3D) regimen of ombitasvir, ABT-450 (identified by AbbVie and Enanta;
      co-dosed with ritonavir) and dasabuvir with ribavirin (RBV) in HCV/HIV-1 co
      infected patients with and without cirrhosis, including HCV treatment
      experienced, receiving atazanavir (ATV)- or raltegravir (RAL)-based ART therapy.
      METHODS: HCV genotype 1-positive treatment-naive or pegIFN/RBV-experienced
      patients, with or without Child-Pugh A cirrhosis, CD4+ count >=200 cells/mm(3) or
      CD4 + % >=14%, and plasma HIV-1 RNA suppressed on stable ART received open-label
      3D + RBV for 12 or 24 weeks. Rates of HCV-sustained virologic response at post
      treatment weeks 4 and 12 (SVR4 and SVR12, respectively) and bilirubin-related
      adverse events (AEs) are reported from post-hoc analyses for subgroups defined by
      treatment duration and ART regimen. RESULTS: The SVR12 rate for patients
      receiving 12 weeks of 3D + RBV was 93.5% with comparable rates in patients
      receiving either ATV (93.8%) or RAL therapy (93.3%) (Table 1). The SVR4 rate for
      the 24-week arm was 96.9% with a single virologic breakthrough at treatment week
      16 in a patient receiving RAL therapy. Patients receiving concomitant ATV had
      more AEs related to indirect hyperbilirubinemia including ocular icterus,
      jaundice and grade 3 or 4 elevations in total bilirubin (predominantly indirect).
      No patient discontinued the study due to AEs, and no serious AEs were reported
      during or after treatment. No patient had a confirmed plasma HIV-1 RNA value
      >=200 copies/mL during the treatment period. CONCLUSIONS: In this first study to
      evaluate an IFN-free regimen in HCV genotype 1-positive treatment-naive and
      experienced patients with HIV-1 co-infection, including those with cirrhosis,
      high rates of SVR were comparable to those with HCV monoinfection. Indirect
      hyperbilirubinemia was consistent with the known ABT-450 inhibition of the
      OATP1B1 bilirubin transporter, RBV-related haemolytic anaemia and inhibitory
      effect of ATV on bilirubin conjugation. The laboratory abnormalities and AEs
      observed did not negatively affect treatment response or lead to treatment
      discontinuation.

PMID- 25394010
TI  - Drug use, HIV, HCV and TB: major interlinked challenges in Eastern Europe and
      Central Asia.
AB  - Eastern Europe and Central Asia have the largest drug epidemic globally and the
      fastest and still expanding HIV epidemic. The Russian Federation and Ukraine
      together account for over 90% of the reported AIDS cases in the region. If small
      in absolute numbers, the epidemics are however significant in prevalence rate in
      most countries of Central Asia. Most heroin and many of the new synthetic or home
      made drugs are injected, which has led to high prevalence levels (up to 90%) of
      HCV infection in people who inject drugs (PWID). The two epidemics of HIV and HCV
      are in turn interlinked with TB and MDR-TB that are highly prevalent among
      marginalized populations in the region. Despite progress in the last two years,
      access to antiretroviral treatment remains far below global levels and increases
      more slowly than new reported cases of HIV. Access to prevention is limited with
      low coverage of needle exchange programs and very low or inexistent access to
      opioid substitutive therapy. There are few exceptions to this situation,
      including Ukraine where harm reduction programs are being scaled up together with
      significant peer outreach programs for PWIDs. This is likely to be the reason why
      the epidemic curves in the Russian Federation and Ukraine are now diverging. The
      region faces many structural, cultural, societal and political obstacles in
      responding to these quadruple epidemics. Without a significantly expanded and
      strengthened response, these epidemics will remain major causes of illness and
      premature deaths in the region. 

PMID- 25394011
TI  - HIV epidemic in Russia and neighbouring countries.
AB  - Reports of HIV/AIDS cases attributed to sexual transmission from foreigners were
      published in the USSR in the mid of 80s. In the initial decade of the epidemic,
      the subtype B was found in men who have sex with men (MSM) population and several
      non-B subtypes were identified in heterosexual persons. The first case of HIV
      infection in intravenous drug users (IVDU) was reported in 1993 and since then a
      specific subtype A and its recombinants invaded the intravenous drug users (IVDU)
      populations of the region with the highest rate in Estonia, Russia and Ukraine.
      The concentrated HIV epidemic in IVDUs is still the main problem in the Eastern
      Europe; however, the rate of heterosexual transmission is increasing and many
      evidences of HIV prevalence rise in MSM are published. UNAIDS estimations for the
      number of HIV-positive persons living in the region range from 980,000 to
      1,300,000 but distribution of HIV-cases is uneven and the prevalence rate of HIV
      infection in separate regions is over 1%. Mass seasonal labour migration from
      Central Asia and Caucasian republics to Russia transmits HIV to these countries.
      Prevention programs in the region are limited, and ART coverage is not more than
      20% of the total HIV-positive population. The lack of concern about the epidemic,
      absence of effective national strategies and limited allocated resources are the
      main barriers to prevention and care in many countries. Local conflicts, rising
      religiosity and discrimination are adverse factors. The near-term forecast for
      the epidemic in the region is pessimistic and further international advocacy is
      needed to improve the situation. 

PMID- 25394012
TI  - Treatment and care of TB across Europe.
AB  - There continues to be profound differences in TB incidences as well as in TB
      treatment and care across Europe in recent years. High TB incidences are observed
      in Eastern Europe and especially among injecting drug users (IDUs), and there are
      large overlaps with a HIV epidemic, which is also far from being under control in
      this region. Further, mortality rates among HIV-positive patients with TB in
      Eastern Europe were in the 2000s 3-5 fold higher compared with other parts of
      Europe. As of 2014, there remain many challenges in the organizational set-up of
      TB care in Eastern Europe and often only limited possibilities of support for the
      vulnerable IDU populations, including in particular opioid substitution therapy.
      Further, high prevalences of multi-drug-resistant TB (MR-TB) are an increasing
      problem in Eastern Europe which in several settings reached beyond 50% among
      patients previously treated for TB. Obviously, this causes problems for immediate
      therapy of the individual patients and for development of secondary resistance
      during therapy. The panel of TB drugs available in TB clinics in Eastern Europe
      is often limited, and a quick TB diagnosis and acknowledgement of the resistance
      pattern to guide initial therapy seems to be a priority. For HIV-positive
      patients in particular, better access to cART may also be an important tool to
      reduce the TB incidence among these patients. Thus, treatment and care of TB
      patients in especially Eastern Europe are facing a variety of diagnostic and
      therapeutic challenges in the coming years. 

PMID- 25394013
TI  - Regional differences in self-reported HIV care and management in the EuroSIDA
      study.
AB  - INTRODUCTION: EuroSIDA has previously reported a poorer clinical prognosis for
      HIV-positive individuals in Eastern Europe (EE) as compared with patients from
      other parts of Europe, not solely explained by differences in patient
      characteristics. We explored regional variability in self-reported HIV management
      at individual EuroSIDA clinics, with a goal of identifying opportunities to
      reduce the apparent inequalities in health. METHODS: A survey
      (www.chip.dk/eurosida/csurvey) on HIV management was conducted in early 2014 in
      all currently active EuroSIDA clinics. Responders in EE were compared with
      clinics in all other EuroSIDA regions combined (non-EE). Characteristics were
      compared between regions using Fishers exact test. RESULTS: A total of 80/97
      clinics responded (82.5%, 12/15 in EE, 68/82 in non-EE). Participating clinics
      reported seeing a total of 133,532 patients [a median of 1300 per clinic (IQR 700
      2399)]. The majority of clinics requested viral load and CD4 measurements at
      least every six months for patients on as well as off ART (EE 66.7%, non-EE 75%,
      p=0,72). Significantly fewer EE clinics performed resistance tests before ART as
      well as upon treatment failure (Figure 1). Half of the EE clinics indicated
      following WHO guidelines (EE 50%, non-EE 7.4%, p<0.0001), whereas most non-EE
      clinics followed EACS guidelines (non-EE 76.5%, EE 41.7%, p=0.017). The majority
      of EE clinics and 1/4 non-EE clinics indicated deferral of ART initiation in
      asymptomatic individuals until CD4 <=350 cells/mm(3) (Figure 1). There were no
      significant regional differences in screening haematology, liver or renal
      function, which the majority of clinics reported to do routinely. However, EE
      clinics reported screening significantly less for cardiovascular disease (CVD),
      and only about half screened for tobacco use, alcohol consumption and drug use
      (Figure 1). Screening for cervical cancer and for anorectal cancer was low in
      both regions (Figure 1). CONCLUSIONS: We found significant regional variability
      in self-reported HIV management across Europe, with less resistance testing,
      screening for CVD and substance use in EE. EE clinics indicated deferral of ART
      initiation for longer than non-EE clinics. Adherence to international guidelines
      for cervical cancer screening was poor in both regions. Whether differences in
      HIV management are reflected in clinical outcomes deserves further investigation.

PMID- 25394014
TI  - Major challenges in clinical management of TB/HIV co-infected patients in Eastern
      Europe compared with Western Europe and Latin America.
AB  - INTRODUCTION: Rates of both TB/HIV co-infection and multi-drug-resistant (MDR) TB
      are increasing in Eastern Europe (EE). Data on the clinical management of TB/HIV
      co-infected patients are scarce. Our aim was to study the clinical
      characteristics of TB/HIV patients in Europe and Latin America (LA) at TB
      diagnosis, identify factors associated with MDR-TB and assess the activity of
      initial TB treatment regimens given the results of drug-susceptibility tests
      (DST). MATERIAL AND METHODS: We enrolled 1413 TB/HIV patients from 62 clinics in
      19 countries in EE, Western Europe (WE), Southern Europe (SE) and LA from January
      2011 to December 2013. Among patients who completed DST within the first month of
      TB therapy, we linked initial TB treatment regimens to the DST results and
      calculated the distribution of patients receiving 0, 1, 2, 3 and >=4 active drugs
      in each region. Risk factors for MDR-TB were identified in logistic regression
      models. RESULTS: Significant differences were observed between EE (n=844), WE
      (n=152), SE (n=164) and LA (n=253) for use of combination antiretroviral therapy
      (cART) at TB diagnosis (17%, 40%, 44% and 35%, p<0.0001), a definite TB diagnosis
      (culture and/or PCR positive for Mycobacterium tuberculosis; 47%, 71%, 72% and
      40%, p<0.0001) and MDR-TB prevalence (34%, 3%, 3% and 11%, p <0.0001 among those
      with DST results). The history of injecting drug use [adjusted OR (aOR) = 2.03,
      (95% CI 1.00-4.09)], prior TB treatment (aOR = 3.42, 95% CI 1.88-6.22) and living
      in EE (aOR = 7.19, 95% CI 3.28-15.78) were associated with MDR-TB. For 569
      patients with available DST, the initial TB treatment contained >=3 active drugs
      in 64% of patients in EE compared with 90-94% of patients in other regions
      (Figure 1a). Had the patients received initial therapy with standard therapy
      [Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RHZE)], the corresponding
      proportions would have been 64% vs. 86-97%, respectively (Figure 1b).
      CONCLUSIONS: In EE, TB/HIV patients had poorer exposure to cART, less often a
      definitive TB diagnosis and more often MDR-TB compared to other parts of Europe
      and LA. Initial TB therapy in EE was sub-optimal, with less than two-thirds of
      patients receiving at least three active drugs, and improved compliance with
      standard RHZE treatment does not seem to be the solution. Improved management of
      TB/HIV patients requires routine use of DST, initial TB therapy according to
      prevailing resistance patterns and more widespread use of cART.

PMID- 25394015
TI  - The cascade of HIV care in Russia, 2011-2013.
AB  - INTRODUCTION: The cascade of HIV care is one of the main tools to assess the
      individual and public health benefits of antiretroviral therapy (ART) and
      identify barriers of treatment as prevention (TasP) concept realization. We aimed
      to characterize the changes in engagement of HIV-positive persons in care in
      Russia during three years (2011-2013). METHODS: We defined seven steps in the
      cascade of care framework: HIV infected (estimation data), HIV diagnosed, linked
      to HIV care, retained in HIV care, need ART, on ART and viral suppressed (VL <
      1000 copies/mL during 12 month ART). Information was extracted from the Federal
      AIDS Centre database and from the national monitoring forms of Rospotrebnadzor
      from the beginning of 2011 to 31 December 2013. RESULTS: Nearly 668,032 HIV
      diagnosed Russian residents were alive by the end of 2013, which consisted 49% of
      the estimated 1,363,330 people living with HIV. Among the alive HIV-diagnosed
      patients, 516,403 (77%) were linked to care and 481,783 (72%) were retained. Of
      163,822 (25% of HIV diagnosed) patients who were eligible for ART, 156,858 (96%)
      were on treatment while 127,054 (81%) had viral suppression. However, only 19% of
      HIV-diagnosed patients achieved viral suppression which is necessary to prevent
      viral transmission. We noted substantial improvements over time in the proportion
      of individuals on ART. The proportion of patients who received ART increased from
      24% in 2011 to 34% in 2013. The most significant leakages of patients during
      three years were on steps: "HIV infected -> HIV diagnosed" (loss -55% in 2011, 
      53% in 2012, and -51% in 2013), "HIV diagnosed -> Linked to care" (-23% yearly)
      and "Retained in care -> Need ART" (-76%, -70%, and -66%, respectively).
      CONCLUSION: The stages of HIV diagnosis and estimation of ART eligibility were
      the most vulnerable to leakage. Encouraging HIV testing and earlier ART
      initiation are needed to maximize the effects of TasP interventions and to
      contain the spread of HIV in Russia.

PMID- 25394016
TI  - Large disparities in HIV treatment cascades between eight European and high
      income countries - analysis of break points.
AB  - INTRODUCTION: Patients on antiretroviral treatment with undetectable HIV RNA
      levels have a significantly lower risk of clinical disease progression and onward
      HIV transmission. This study aimed to estimate and compare the percentage of all
      HIV-positive people who are diagnosed, are linked to care, are taking
      antiretroviral treatment and have undetectable HIV RNA, in eight European and
      high-income countries: the United States, the United Kingdom, France, the
      Netherlands, Denmark, Australia, British Columbia (Canada) and Georgia. MATERIALS
      AND METHODS: For each country, the number of people in five key stages of the HIV
      treatment cascade was collected: 1. HIV infected, 2. Known to be HIV positive, 3.
      Linked to care, 4. Taking antiretroviral treatment, and 5. Having undetectable
      HIV RNA. Estimates were extracted from national reports (1-3), the UNAIDS
      database, conference proceedings (4) and peer-reviewed articles (5-7). The
      quality of the estimates and reporting methods were assessed individually for
      each country, with selection criteria such as availability of nationwide database
      and routinely collected data. Treatment cascades were constructed using estimates
      from 2010 to 2012. RESULTS: As shown in Table 1, the percentage of all infected
      people with undetectable HIV RNA ranged from 20% in Georgia to 59% in Denmark. Of
      the high-income countries, the United States has the lowest percentage of
      individuals with undetectable viral load (25% to median 52%), associated with the
      highest HIV incidence rate (15.30 per 100,000 to median 6.07 per 100,000). The
      pattern of the cascades differed between countries: in the United States, there
      is a fall from 66% to 33% (-33%) between linkage to care and start of
      antiretroviral treatment. However, in Georgia, the greatest loss in continuum was
      zat diagnosis, with 48% of undiagnosed HIV-positive individuals. CONCLUSIONS:
      There are great disparities among European and high-income countries in the
      percentage of HIV-positive individual with undetectable HIV RNA. Furthermore, the
      treatment cascades show different key break points, underlying inequalities in
      HIV care between countries.

PMID- 25394017
TI  - Management of drug-resistant TB in patients with HIV co-infection.
AB  - The World Health Organization estimates that 450,000 cases of drug-resistant (DR)
      tuberculosis (TB) occurred worldwide in 2012. In South Africa, over 15,000 cases
      were diagnosed. Over half of patients in South Africa with TB are HIV co
      infected. The management of drug-resistant TB is complex, prolonged, costly,
      associated with multiple toxicities and thus difficult for patients to complete.
      Disengagement from follow-up is common. Co-infection with HIV presents a number
      of additional challenges in DR TB management including shared drug toxicities
      between TB and HIV drugs, potential for increased drug toxicity due to underlying
      HIV-related organ disease such as nephropathy, pharmacokinetic drug-drug
      interactions and immune reconstitution inflammatory syndrome including
      manifestations at extrapulmonary sites. Mortality with multi-drug-resistant (MDR)
      TB is higher in HIV-positive patients. Mortality is similar for HIV-positive and
      uninfected patients with extremely drug-resistant (XDR) TB, given the current
      lack of effective therapy, with over 70% case fatality by five years. ART
      improves survival in patients with DR TB, and timing of ART initiation in
      relation to TB treatment should be similar to patients with drug-susceptible TB.
      New (e.g. bedaquiline and delaminid) and repurposed (e.g. linezolid and
      clofazamine) drugs promise to improve the prognosis of patients with DR TB.
      Several clinical trials of new regimens are ongoing and planned, and early data
      from the Bedaquiline Clinical Access Programme in South Africa suggests much
      improved short-term outcomes when bedaquiline +/- linezolid and/or clofazamine
      are included in the regimen of patients with XDR and pre-XDR TB including
      patients with HIV co-infection. There are important considerations with respect
      to QT prolongation and ART drug interactions related to bedaquiline that need to
      be factored in treatment decisions and monitoring plans. 

PMID- 25394018
TI  - CD4 cell count and the risk of infective and non-infective serious non-AIDS
      events in HIV-positive persons seen for care in Italy.
AB  - INTRODUCTION: Serious non-AIDS events (SNAE) are frequent in HIV patients
      receiving cART. Current CD4 count was shown to be more strongly associated with
      infective compared to not-infective SNAE and unable to predict cardiovascular
      events. We investigated the relationship between baseline and current CD4 count
      and the risk of both infective and non-infective SNAE in HIV-positive patients
      according to current ART use. METHODS: We included all HIV-positive persons
      enrolled in the ICONA Foundation Study cohort who had at least one follow-up
      visit. SNAE were grouped in infective (pneumonia, sepsis, endocarditis and
      meningitis) and non-infective (malignancies, chronic kidney disease,
      cardiovascular events, hepatic events and pancreatitis) aetiology. Incidence of
      these event groups were calculated overall and according to baseline and current
      CD4 count (grouped as 0-200, 201-350, 351-500, 501-750, and >750 cells/mm(3)).
      Participants' follow-up accrued from the date of enrolment (baseline) to a
      diagnosis of SNAE or their last visit. An event was defined the first time one of
      the considered SNAE occurred so that each person contributed a single event. A
      Poisson regression model for each of the two endpoints was used. RESULTS: A total
      of 10,822 patients were included (25.3% females, 38.2% heterosexuals) and 26.6%
      had hepatitis co-infections. Median age was 36 (IQR 31-42) years. Overall, 423
      not-infective and 385 infective SNAE were included. The most frequent non
      infective SNAE were malignancies (n=202) and the most frequent infective SNAE
      were pneumonia (n=289). Crude rates of non-infective SNAE were 0.78, 1.08 and
      0.80/100 PYFU, and those of infective SNAE were 1.00, 0.51 and 0.66/100 PYFU in
      ART naive, currently off and currently on ART patients, respectively. Higher
      current CD4 count was associated with reduced risk of both infective and non
      infective SNAE in naives and in patients on ART (Table 1). The association was
      less strong in the group which suspended ART (for non-infective SNAE the p value
      for interaction between current log-CD4 and ART-status, p=0.004). Conversely, we
      found no association between baseline CD4 count and risk of non-infective SNAE in
      people treated with ART (p value for interaction = 0.0001). When CVD were
      considered separately, there was no association with CD4 count (not shown).
      CONCLUSIONS: Our findings show that, differently from ART naive, in ART-treated
      patients, non-infective SNAE are predicted by current but not by baseline CD4,
      suggesting that immune restoration is crucial to prevent these events.

PMID- 25394019
TI  - Predictive value of prostate-specific antigen for prostate cancer: a nested case
      control study in EuroSIDA.
AB  - INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than
      in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this
      population is not well defined and may have higher false negative rates than in
      HIV- men. We aimed to describe the kinetics and predictive value of PSA in HIV+
      men. METHODS: Men with PCa (n=21) and up to two matched controls (n=40) with
      prospectively stored plasma samples before PCa (or matched date in controls) were
      selected. Cases and controls were matched on date of first and last sample, age,
      region of residence and CD4 count at first sample date. Total PSA (tPSA), free
      PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured.
      Conditional logistic regression models investigated associations between markers
      and PCa. Sensitivity and specificity of using tPSA >4 ug/L to predict PCa was
      calculated. Mixed models were used to describe kinetics. RESULTS: Sixty-one men
      were included with a median six (IQR 2-9) years follow-up. Time between last
      sample and PCa was seven (4-11) months. Cases and controls were well matched at
      first sample, with a median age of 51 (IQR 48-57) and CD4 of 437 (243-610)
      cells/mm(3). Median tPSA [2.8 (IQR: 1.6-4.6) and 0.8 (0.5-1.2) ug/L] and fPSA
      [0.4 (0.2-0.8) and 0.3 (0.2-0.4) ug/L] levels were higher in cases than controls
      at first sample. Both tPSA and fPSA increased significantly over time in cases
      (Figure 1), to a median at last sample of 6.1 (4.7-9.5) and 0.9 (0.6-1.3) ug/L,
      respectively, but were stable in controls, with a median at last sample of 0.8
      (0.5-1.4) and 0.2 (0.2-0.4) ug/L (Figure). Higher levels of tPSA and fPSA were
      associated with higher odds of PCa at first sample [OR for 2-fold higher 4.7 (CI:
      1.7-12.9) and 5.4 (1.7-17.4)]. Elevated tPSA values in cases were detectable >=5
      years before PCa (p<0.01). Testosterone [overall median 19.4 (IQR 15.3-23.9)
      nmol/L at first sample) and SHBG [50.0 (34.0-66.0) nmol/L] levels were similar in
      cases and controls at first and last sample (all p>0.7). The most informative
      predictor of PCa was tPSA (AUC=0.9), followed by fPSA (0.8). Testosterone (AUC =
      0.5) and SHBG (0.5) were poor predictors of PCa. Overall, tPSA level >4 ug/L had
      99% specificity and 37% sensitivity. Performance was best in the year prior to
      PCa (specificity: 99%, sensitivity: 88%). CONCLUSIONS: PSA was highly predictive
      of PCa in HIV+ men. Our results indicate that PSA screening in HIV+ men may be
      useful, and further work is needed to identify potentially age-related cut-offs
      to maximize sensitivity and specificity to identify those for further evaluation
      at early stages of PCa.

PMID- 25394020
TI  - Effects of age on symptom burden, mental health and quality of life amongst
      people with HIV in the UK.
AB  - INTRODUCTION: The evolving HIV epidemic, coupled with advances in HIV treatment,
      has resulted in an ageing HIV-diagnosed population. It has been suggested that
      adverse physical and psychological effects of HIV may be higher among older
      people. However, few studies have examined the effect of older age on well-being
      for people with HIV. MATERIALS AND METHODS: The ASTRA study included 3258 HIV
      diagnosed individuals (2248 MSM; 373 heterosexual men; 637 women) recruited from
      eight UK clinics in 2011-12 (64% response rate). Participants completed a
      questionnaire that included standard inventories on symptoms and health-related
      quality of life (HrQoL). Associations of age group with: physical symptom
      distress (reporting significant distress for >=1 of 26 symptoms), depression and
      anxiety (score >=10 on PHQ-9 and GAD-7, respectively) and HrQoL problem
      (reporting problems on >=1 of 5 Eurqol-5D domains) were assessed; adjustment was
      made for gender/sexuality and time with diagnosed HIV. RESULTS: Of all
      participants, 87% were taking ART, 76% had VL <=50c/mL and 19% had CD4
      <350/mm(3). Mean age was 45 years (range 18-88) with 5% <30, 23% 30-39, 43% 40
      49, 22% 50-59 and 7% >=60 years. The most prevalent distressing physical symptoms
      were: lack of energy/tiredness (26%), difficulty sleeping (24%), muscle
      ache/joint pain (21%) and pain (18%). With older age, there was no clear trend in
      prevalence of physical symptom distress, but prevalence of depression and anxiety
      decreased, while prevalence of HrQoL problems increased. This pattern remained
      after adjustment for gender/sexuality and time diagnosed with HIV. The increase
      with age in overall prevalence of HrQoL problem was due to increased problems for
      "mobility," "self-care" and "performing usual activities" domains, not an
      increase in "depression/anxiety." Longer time with diagnosed HIV was strongly
      associated with higher prevalence of all symptoms measures and HrQoL problem
      (p<0.001 for trend, adjusted models). CONCLUSIONS: Physical and psychological
      symptoms are common among people living with HIV, but the burden of these
      symptoms is not highest among the older age group. While HrQoL tended to worsen
      with older age, physical symptom distress did not, and mental health improved.
      This may reflect greater resilience in older adults, or the potential for
      "successful ageing": maintaining mental health despite age-related health losses.

PMID- 25394021
TI  - Lack of association between use of efavirenz and death from suicide: evidence
      from the D:A:D study.
AB  - INTRODUCTION: A recent meta-analysis of 4 RCTs showed an increased rate of
      suicidality events (suicidal ideation or attempted/completed suicide) associated
      with efavirenz (EFV) compared to other regimens, but only a trend towards a
      higher rate of completed/attempted suicides, as only 17 events occurred. We
      investigated the association between EFV use and completed suicide. MATERIALS AND
      METHODS: All D:A:D participants were followed from study entry to the first of
      death, last study visit or 1 February 2013. Deaths are centrally validated using
      cause of death methodology, which assigns underlying, immediate and up to four
      contributing causes of death. Two endpoints were considered: 1) suicide or
      psychiatric disease as the underlying cause, and 2) suicide or psychiatric
      disease mentioned as an underlying, immediate or contributing cause of death
      (anywhere). Adjusted rate ratios were calculated using Poisson regression.
      RESULTS: A total of 4420 deaths occurred in 49,717 people over 371,333 person
      years (PY) (rate 11.9 per 1000 PY; 95% CI 11.6-12.3). A total of 193 deaths (rate
      0.52; 0.45-0.59) had an underlying cause of suicide or psychiatric disease, and
      482 deaths (1.30; 1.18-1.41) had suicide or psychiatric disease mentioned
      anywhere. A strong association with current CD4 count was seen: for suicide or
      psychiatric disease mentioned anywhere, rates were: 3.18 (2.55-3.80) for <200
      cells/uL, 1.60 (1.29-1.90) for 201-350 cells/uL, 1.07 (0.86-1.29) for 351-500
      cells/uL, 0.95 (0.80-1.09) for >500 cells/uL and 1.30 (1.18-1.41) for unknown.
      Highest rate of suicide or psychiatric deaths were seen in ART-experienced people
      currently off ART, but no differences were seen according to current ART regimen,
      which remained after adjustment (Table 1). Consistent results were obtained when
      considering additional endpoints of suicide alone as the underlying cause and
      death from suicide or any possibly related cause (psychiatric disease, drug
      overdose, alcohol related, accidental or violent), as well as considering recent
      EFV use in the previous 3 and 6 months. CONCLUSIONS: The finding of no higher
      death rates from suicide amongst those receiving EFV is reassuring. However,
      there is likely confounding by indication in our observational study. In light of
      conflicting results from RCTs, this potentially could suggest that in clinical
      practice EFV may be less frequently prescribed in those with underlying
      psychiatric conditions.

PMID- 25394022
TI  - Adverse events: ART and the kidney: alterations in renal function and renal
      toxicity.
AB  - Renal dysfunction is common in HIV-positive patients who receive antiretroviral
      therapy (ART). Several antiretrovirals have been associated with kidney disease
      progression, inhibition of renal tubular transporters that mediate creatinine
      secretion or impaired reabsorption of phosphate and low-molecular weight
      proteins. These aberrations of renal function are typically non-treatment
      limiting and of unclear clinical significance. By contrast, severe renal toxicity
      is infrequent in well-managed patents. Tenofovir-DF and atazanavir may cause
      acute tubular injury, tubule-interstitial nephritis or nephrolithiasis.
      Discontinuation of the offending drug is required to mitigate the adverse effects
      on kidney or bone. This presentation will discuss ART-associated changes in renal
      function and treatment-limiting renal toxicity in terms of incidence, risk
      factors, putative mechanism and provide recommendations for clinical practice. 

PMID- 25394023
TI  - A clinically useful risk-score for chronic kidney disease in HIV infection.
AB  - INTRODUCTION: Development of a simple, widely applicable risk score for chronic
      kidney disease (CKD) allows comparisons of risks or benefits of starting
      potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen.
      MATERIALS AND METHODS: A total of 18,055 HIV-positive persons from the Data on
      Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs)
      >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir
      (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other
      boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73
      m(2) after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months
      apart) eGFR <60. Poisson regression was used to develop a score predicting low
      (<0 points), medium (1-4 points) and high (>5 points) risk of developing CKD.
      Increased incidence of CKD associated with starting ARVs was modelled by
      including ARVs as time-updated variables. The risk score was externally validated
      on two independent cohorts. RESULTS: A total of 641 persons developed CKD during
      103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7-6.7). Older age, intravenous
      drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4
      nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were
      included in the risk score (Figure 1). The incidence of CKD in those at low,
      medium and high risk was 0.8/1000 PYFU (95% CI 0.6-1.0), 5.6 (95% CI 4.5-6.7) and
      37.4 (95% CI 34.0-40.7) (Figure 1). The risk score showed good discrimination
      (Harrell's c statistic 0.92, 95% CI 0.90-0.93). The number needed to harm (NNTH)
      in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those
      with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low,
      medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally
      validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events,
      incidence 5.1/1000 PYFU; 95% CI 4.1-6.1) and 2013 persons from the control arms
      of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5-5.1). External
      validation showed consistent CKD rates across risk groups (Figure 2).
      INTERPRETATION: Traditional and HIV-related risk factors were predictive of CKD;
      all are routinely available, making the risk score easy to incorporate into
      clinical practise and of direct relevance for clinical decision making. NNTH in
      persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and
      alternative ARVs may be more appropriate.

PMID- 25394024
TI  - Cardiovascular risk evaluation of HIV-positive patients in a case-control study:
      comparison of the D:A:D and Framingham equations.
AB  - INTRODUCTION: Patients with HIV infection are at increased risk of developing
      cardiovascular disease (CVD) due to complex interactions between traditional CVD
      risk factors, antiretroviral therapy (ART) and HIV infection itself (1).
      Prevention of CVD is essential as it remains the most common serious non-AIDS
      event and contributes significantly to all-cause mortality. A cardiovascular risk
      assessment model tailored to HIV population is thus essential. MATERIALS AND
      METHODS: We conducted a retrospective case-control study within the HIV cohort of
      the Saint-Pierre Hospital, Brussels. Cases (n=73) presented a first CVD (ischemic
      heart disease or stroke) between January 2002 and December 2012. Controls (n=142)
      were patients without any CVD and were matched for age, race, sex and follow-up
      duration. We used Wilcoxon test to identify predictors of cardiovascular risk
      among the data collected. We compared Framingham (2) and DAD (Data Collection on
      Adverse Events of anti-HIV drugs) (3) equations calculated in all patients at
      time of event, two, four and six years before. We then simulated the impact on
      the DAD scores if different therapeutic interventions had been introduced when
      patient cardiovascular risk at ten years exceeded 20%. RESULTS: Comparison of
      cases and controls showed that C-reactive protein (CRP) >3 mg/L (p=0.008) and HIV
      viral load >50 copies/ml (p=0.007) at time of event, as well as slower increase
      in CD4 cell count (p=0.035), were significantly more frequent in cases. DAD and
      Framingham median scores in cases and controls are shown in Figure 1 and Table 1.
      Smoking cessation lowered the DAD score of cases at time of event from 21.6% to
      18.3%, modification of ART (discontinuation of indinavir, lopinavir and abacavir)
      lowered it from 21.6% to 17%, while both interventions with control of blood
      pressure and cholesterol lowered it from 21.6% to 12.4%. CONCLUSIONS: Increased
      CRP levels, uncontrolled HIV viral load at time of event and slower immunologic
      response were found to be associated with increased CVD risk. DAD score in cases
      increased more and faster over time than the Framingham score and seems therefore
      to be more accurate in identifying HIV-positive patients at high risk of CVD.
      Different therapeutic interventions could have led to a significant reduction of
      the DAD score in these patients and should remain a priority in patient
      management.

PMID- 25394025
TI  - Gender differences in HIV-positive persons in use of cardiovascular disease
      related interventions: D:A:D study.
AB  - INTRODUCTION: There is a lack of data on potential gender differences in the use
      of interventions to prevent and treat cardiovascular disease (CVD) in HIV
      positive individuals. We investigated whether such differences exist in the D:A:D
      study. MATERIALS AND METHODS: Follow-up was from 01/02/99 until the earliest of
      death, 6 months after last visit or 01/02/13. Rates of initiation of lipid
      lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti
      hypertensives and receipt of invasive cardiovascular procedures (ICPs; bypass,
      angioplasty, endarterectomy) were calculated in those without a myocardial
      infarction (MI) or stroke at baseline, overall and in groups known to be at
      higher CVD risk: (i) age >50, (ii) total cholesterol >6.2 mmol/l, (iii)
      triglyceride >2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or
      (vii) predicted 10-year CVD risk >10%. Poisson regression was used to assess
      whether rates of initiation were higher in men than women, after adjustment for
      these factors. RESULTS: At enrolment, women (n=13,039; median (interquartile
      range) 34 (29-40) years) were younger than men (n=36,664, 39 (33-46) years,
      p=0.001), and were less likely to be current smokers (29% vs. 39%, p=0.0001), to
      have diabetes (2% vs. 3%, p=0.0001) or to have hypertension (7% vs. 11%,
      p=0.0001). Of 49,071 individuals without a MI/stroke at enrolment, 0.6% women vs.
      2.1% men experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall,
      women received ICPs at a rate of 0.07/100 person-years (PYRS) compared to
      0.29/100 PYRS in men. Similarly, the rates of initiation of LLDs (1.28 vs. 2.46),
      anti-hypertensives (1.11 vs. 1.38) and ACEIs (0.82 vs. 1.37) were all
      significantly lower in women than men (Table 1). As expected, initiation rates of
      each intervention were higher in the groups determined to be at moderate/high CVD
      risk; however, within each high-risk group, initiation rates of most
      interventions (with the exception of anti-hypertensives) were generally lower in
      women than men. These gender differences persisted after adjustment for potential
      confounders (Table 1). CONCLUSION: Use of most CVD interventions was lower among
      women than men in the D:A:D study. Our findings suggest that actions should be
      taken to ensure that both men and women are monitored for CVD and, if eligible,
      receive appropriate CVD interventions.

PMID- 25394026
TI  - Resistance: what is new and on the horizon, and a time to teach old dogs new
      tricks?
AB  - Understanding HIV drug resistance has played a key role in the success of
      antiretroviral therapy. This knowledge allowed for the prediction of resistance
      evolution when a specific drug or combinations of drugs were administered,
      informing strategies implemented for initial and subsequent drug regimens.
      Resistance testing of individual patients detects transmitted as well as acquired
      drug resistance as a result of treatment failure, leading to improved treatment
      choices in drug naive and drug experienced patients accordingly. The last two
      decades has seen a great deal of evolution, improvement and change in the care of
      HIV-positive individuals. Much of this was aimed at preventing, reducing or
      minimizing the impact of HIV drug resistance. Drugs with much improved resistance
      characteristics were designed and gained widespread use, as well as those with
      superior pharmacology and toxicity profiles assisting in better adherence and far
      reduced failure rates. Patient management strategies and monitoring technologies
      were refined, and education of clinicians and patients on optimal aspects of care
      routinely was implemented. All these have led to a new world of HIV clinical care
      and require a rethinking of how best to use our knowledge of resistance and when,
      how and in whom to test for it. What lays ahead for HIV drug resistance in the
      near and distant future, and is it time to teach old dogs new tricks? 

PMID- 25394027
TI  - The R263K mutation in HIV integrase that is selected by dolutegravir may actually
      prevent clinically relevant resistance to this compound.
AB  - INTRODUCTION: Drug resistance against dolutegravir (DTG) or the nucleosides with
      which it has been co-administered has never been observed in patients receiving
      this drug in first-line therapy. In contrast, a R263K mutation that confers low
      level resistance (3-4 fold) to DTG has been selected by DTG in culture. Our group
      has ascribed the absence of resistance to DTG to the high fitness cost exacted by
      the R263K mutation and an inability of HIV to generate compensatory mutations.
      MATERIALS AND METHODS: We generated recombinant integrase enzymes and viruses
      containing various combinations of mutations and studied these enzymatically and
      in culture. We also selected for resistance against raltegravir (RAL) using
      viruses containing the R263K mutation. RESULTS: The R263K mutation alone
      conferred an approximate 3-fold level of resistance to DTG and a 40% loss in
      viral replicative capacity and recombinant integrase activity. Secondary
      mutations selected at positions H51Y or E138K did not individually affect either
      enzyme activity or DTG resistance, but the combination of R263K together with
      H51Y or E138K increased DTG resistance to about 7-fold accompanied by a ~75% loss
      in each of viral replication capacity, and both in vitro and in vivo integrase
      activity. Conversely, combinations of R263K together with multiple resistance
      mutations for RAL and/or EVG at positions 92,143, 148 and 155 resulted in even
      further diminished enzymatic activity that may be incompatible with viral
      survival. Modelling of the 3-dimensional structure of integrase suggests that
      R263K is located in a region that may not permit further mutagenesis if secondary
      mutations at H51Y or E138K are also present. Moreover, integrase that contains
      R263K together with substitutions at positions 92, 143, 148 and 155 may be
      enzymatically inactive. The use of the R263K-containing virus to select for
      resistance to RAL led to the appearance of RAL-containing mutations but the loss
      of R263K. CONCLUSIONS: Secondary mutations to R263K following selection with DTG
      have all led to diminished viral and enzymatic fitness, helping to explain why
      resistance to DTG in previously drug-naive subjects has never been observed. The
      use of DTG in first-line therapy may prevent the facile development of drug
      resistance and help to forestall ongoing HIV transmission.

PMID- 25394028
TI  - First prospective comparison of genotypic vs phenotypic tropism assays in
      predicting virologic responses to Maraviroc (MVC) in a phase 3 study: MODERN.
AB  - INTRODUCTION: MODERN (A4001095) was the first prospective phase 3 study comparing
      genotype vs phenotype (TrofileTM) tropism assessments. MATERIALS AND METHODS:
      Treatment-naive adults with HIV-1 RNA >1000 copies/mL were randomized 1:1 at
      screening to either genotype or Trofile for tropism assessment. Genotype was
      determined using the geno2pheno algorithm to assess triplicate HIV-1 gp120 V3
      loop sequences (plasma); false-positive rate=10%. R5-virus-infected subjects were
      then randomized 1:1 to receive Maraviroc (MVC) 150 mg QD or Truvada 200/300 mg QD
      each with DRV/r 800/100 mg QD. Tropism of screening samples from enrolled
      subjects was also retrospectively determined using the alternate testing method.
      Positive predictive values (PPV) were estimated by%R5 subjects with Week 48 HIV-1
      RNA < 50 c/mL. PPV for each assay was estimated using the response rate among
      those randomized to that assay and using model-based response estimates in those
      with R5 by that assay (at screening or retest). RESULTS: The observed response
      rate was 146/181 (80.7%) for genotype vs 160/215 (74.4%) for Trofile
      (stratification adjusted difference=6.9%, 95% CI 1.3% to 15%). The model-based
      estimates of PPV (+/-SE) were 79.1% (+/-2.42) and 76.3% (+/-2.38), respectively
      (difference = 2.8%, 95% CI -2.1% to 7.2%). There was no difference in response
      rate between assays in the Truvada arm (observed difference=- 0.1%, 95% CI -6.8%
      to 6.6%). Most enrolled subjects had R5 results at screening using both assays
      (285/396 (72%)), and of these subjects, 79.3% (226/285) had HIV-1 RNA <50 c/mL at
      week 48 (Table 1). The few subjects classified as non-R5 by the alternate assay
      had similar virologic responses to the concordant R5 group. CONCLUSION: There was
      a higher MVC response rate and model-based positive predictive value with
      genotype compared to Trofile, but this difference did not reach statistical
      significance. The majority of subjects had concordant R5 tropism results. Either
      phenotype or genotype can effectively predict MVC response.

PMID- 25394029
TI  - Genotypic tropism testing in proviral DNA to guide maraviroc initiation in
      aviremic subjects: 48-week analysis of the PROTEST study.
AB  - INTRODUCTION: In a previous interim 24-week virological safety analysis of the
      PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse
      transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism
      testing of proviral HIV-1 DNA was associated with low rates of virological
      failure. Here we present the final 48-week analysis of the study. METHODS:
      PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910)
      carried on in 24 HIV care centres in Spain. Maraviroc-naive HIV-1-positive adults
      with HIV-1 RNA (VL) <50 c/mL on stable ART during the previous 6 months,
      requiring an ART change due to toxicity, with no antiretroviral resistance to the
      ART started, and R5 HIV by proviral DNA genotypic tropism testing (defined as a
      G2P FPR >10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48
      weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent
      adherence was calculated as: (# pills taken/# pills prescribed during the
      previous week)*100. RESULTS: Tropism results were available from 141/175 (80.6%)
      subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in
      the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had
      CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+
      counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143
      cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%)
      and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change
      were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity
      (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%),
      AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained
      VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%)
      withdrew informed consent, one (1%) had a R5->X4 shift in HIV tropism between the
      screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed
      an ART-related adverse event (rash), two (3%) died due to non-study-related
      causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five
      (7%) developed protocol-defined virological failure, although two of them
      regained VL<50 c/mL with the same MVC regimen (Table 1). CONCLUSIONS: Initiation
      of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of
      proviral HIV-1 DNA is associated with low rates of virological failure up to one
      year.

PMID- 25394030
TI  - Treatment as Prevention: unanswered questions and progress to date.
AB  - Prevention of HIV infection has recently acquired new effective tools, based on
      the provision of antiretrovirals, to both decrease the "source" of HIV infection
      and/or to decrease host susceptibility to HIV infection. The milestone concept of
      using antiretrovirals for prevention has been tested already in the 1990s, to
      interrupt maternal-child. The suggestion of using antiretrovirals to decrease
      inter-human HIV transmission was born already in 2006, and definitely proven by a
      randomized controlled study on HIV-discordant couples demonstrating an
      astonishing 96% efficacy, and with numerous studies proving the efficacy of pre
      exposure prophylaxis. It now appears clear that antiretroviral therapy not only
      provides clinical benefit to the individual (although the exact starting time
      remains controversial, in terms of risk-benefit ratio and public health policy)
      but has the potential of decreasing the incidence of new infections at a
      population level. The concept of Treatment as Prevention is now gaining momentum,
      as a way to progressively end the AIDS epidemic by expanding the access to
      antiretrovirals, with "test and treat" being the ultimate possibility, although
      not already tested in the field and with huge implementation barriers. The
      presentation will deal with successes, failures, and foreseen barriers of using
      antiretrovirals for prevention, at the individual and population level, also
      including the social issues, the need to target key-affected populations, and,
      finally, the perspectives of new technologies under development. 

PMID- 25394031
TI  - A community perspective on pre-exposure prophylaxis.
AB  - The history of pre-exposure prophylaxis (PrEP) is notable for being a community
      rather than industry-driven development. This talk will review this history,
      covering factors that include community demand, study results, regulatory
      challenges, commercial interests and practical issues of public health. It will
      also look at some of the controversies that appear to limit broader access, and
      important changes since US approval for PrEP in 2012. If PrEP had been discovered
      in the 1980s, the demand for access is likely to have been very different and it
      would now be universally available. Yet in many health settings, the willingness
      to include the option of PrEP appears to be inversely correlated with the
      increasingly impressive data showing its effectiveness. The limitations of
      condoms are shown in continued rates of new HIV infections in high-risk
      populations. These rates have remained persistently high for the last decade,
      even with the dramatic impact of treatment as prevention (TasP) on reducing
      further transmission. Within the last year, the polarized debate about PrEP
      appears to be shifting to a middle ground focused on individual choice. Together
      with TasP, this has started a new dialogue on the potential benefits on quality
      of life. This has brought a new focus on the cumulative and largely unmeasured
      impact for HIV negative gay men who live for decades focused on a fear of HIV.
      Looking forwards, the rate-limiting steps of cost and adherence have the
      potential to be overcome with lower priced generic tenofovir in 2017 and the
      development of long-acting formulations. 

PMID- 25394032
TI  - Efavirenz 400 mg daily remains non-inferior to 600 mg: 96 week data from the
      double-blind, placebo-controlled ENCORE1 study.
AB  - INTRODUCTION: ENCORE1 compared the efficacy and safety of reduced versus standard
      dose efavirenz (EFV) with tenofovir/emtricitabine (TDF/FTC) as first-line HIV
      therapy. The primary analysis at 48 weeks showed 400 mg EFV was safe and
      virologically non-inferior to 600 mg. This analysis explores over 96 weeks the
      durability of efficacy and safety. MATERIALS AND METHODS: A multinational, double
      blind, placebo-controlled, non-inferiority trial in treatment-naive HIV-positive
      adults randomized to TDF/FTC plus reduced (400 mg, EFV400) or standard dose (600
      mg, EFV600) EFV. The difference between proportions of participants with plasma
      HIV RNA (VL) <200 log10 copies/mL by intention-to-treat (ITT missing=failure) was
      compared using a non-inferiority margin of -10%. Non-inferiority was also
      examined in per protocol (PP) and non-completer = failure (NC=F) populations.
      Adverse events (AEs) and serious adverse events (SAEs) were summarized by
      treatment arm. RESULTS: The ITT population comprised 630 patients (EFV400 = 321;
      EFV600 = 309); 32% were female; 37%, 33% and 30% were African, Asian and
      Caucasian, respectively. A total of 585 (EFV400 = 299; EFV600 = 286) completed 96
      weeks on randomized therapy. At 96 weeks, proportions with VL <200 copies/mL were
      EFV400 (90.0%) and EFV600 (90.6%) (difference -0.6; 95% CI -5.2 to 4.0; p=0.72)
      demonstrating continued non-inferiority. Non-inferior efficacy was also observed
      for VL thresholds of <50 and <400 copies/mL irrespective of baseline VL (<100,000
      versus >=100,000 copies/mL). There was no between-arm difference in time to loss
      of virological response (>200 copies/mL) (p=0.47) or mean change from baseline VL
      (p=0.74). Mean change from baseline in CD4 T-cell counts at week 96 remained
      significantly higher for EFV400 than EFV600 (difference 25 cells/uL; 95% CI 2-48;
      p=0.03). There was no difference in the frequency or severity of AEs (EFV400 =
      89.4%, EFV600 = 89.3%; difference 0.09; 95% CI -4.73 to 4.90; p=0.97). The
      proportions ever reporting an AE definitely or probably EFV-related were EFV400
      (37.7%) and EFV600 (47.9%) (difference -10.2%; 95% CI -17.9 to -2.51; p=0.01).
      SAEs did not differ in frequency (EFV400 = 7.5%, EFV600 = 10.4%; difference 
      2.9%; 95% CI -7.3 to 1.6; p=0.20). CONCLUSIONS: Non-inferiority of EFV 400 mg to
      EFV 600 mg when combined with TDF/FTC as initial HIV therapy was confirmed at
      week 96. Both doses demonstrated similar safety profiles. These results support
      the use of a lower EFV dose as part of routine HIV management.

PMID- 25394033
TI  - Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance
      antiretroviral therapy with the guidance of therapeutic drug monitoring.
AB  - INTRODUCTION: Wide inter-patient variation of plasma efavirenz (EFV)
      concentrations has been observed, and a substantial proportion of HIV-positive
      patients may have unnecessarily higher plasma EFV concentrations than recommended
      while receiving EFV-containing combination antiretroviral therapy (cART) at the
      currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV
      has recently been demonstrated to be as efficacious as the recommended 600 mg
      when combined with tenofovir/mtricitabine in a multinational clinical trial, with
      a lower incidence of adverse effects. We aimed to use a therapeutic drug
      monitoring (TDM)-guided strategy to optimize the EFV dose in HIV-positive
      Taiwanese patients. MATERIALS AND METHODS: The plasma EFV concentrations at 12
      hours (C12) after taking the previous dose were determined among HIV-positive
      adults who had received EFV-containing cART with viral suppression (plasma HIV
      RNA load (PVL) <200 copies/mL). For those with EFV C12 >2.0 mg/L, EFV (Stocrit,
      MSD) was reduced to half a tablet daily. Determinations of EFV C12 were repeated
      4-12 weeks after switch using high-performance liquid chromatography. CYP2B6
      G516T polymorphisms were determined using polymerase-chain-reaction restriction
      fragment-length polymorphism. RESULTS: Between April 2013 and June 2014, 111
      patients (95.5% male; mean age, 39 years; 96.4% with PVL <40 copies/ml; 26.4%
      HBsAg-positive and 7.5% anti-HCV-positive) with plasma C12 efavirenz >2.0 mg/L
      were switched to a reduced dose (1/2# hs) of EFV; 45.5% of them had CYP2B6 G516T
      or TT genotypes; and 32.4% weighed 60 kg or less. The mean baseline EFV C12
      before switch was 3.65 mg/L (interquartile range (IQR), 2.62-4.17) for 111
      patients, which decreased to 1.96 mg/L (IQR, 1.53-2.33) for 64 patients who had
      completed follow-up of C12 EFV 4 weeks after switch, with a reduction of 49.4%
      (IQR, 38.9-57.0%). As of 10 July, 2014, all of the 38 patients (100%) who had
      completed at least one follow-up of PVL achieved undetectable PVL (<40 copies/ml)
      following switch to a reduced dose of EFV after a mean observation of 13 weeks
      (IQR, 7-15 weeks). CONCLUSIONS: Switch to cART containing a half tablet of EFV
      (1/2#) in HIV-positive Taiwanese patients with higher plasma EFV concentrations
      who had achieved viral suppression could maintain successful viral suppression
      with the guidance of TDM.

PMID- 25394034
TI  - The PROTEA trial: darunavir/ritonavir with or without nucleoside analogues, for
      patients with HIV-1 RNA below 50 copies/mL.
AB  - INTRODUCTION: In previous studies, protease inhibitor (PI) monotherapy has shown
      trends for higher low-level elevations in HIV-1 RNA compared to triple therapy,
      but no increase in the risk of drug resistance. METHODS: A total of 273 patients
      with HIV-1 RNA <50 copies/mL for over 24 weeks on current antiretrovirals
      switched to DRV/r (darunavir/ritonavir) 800/100 mg once-daily, either as
      monotherapy (n=137) or with 2NRTIs (nucleoside reverse-transcriptase inhibitors)
      (n=136), after a 4 week run-in phase with DRV/r + 2NRTI. Treatment failure was
      defined as HIV-1 RNA levels above 50 copies/mL (FDA Snapshot method) by Week 48,
      or switches off study treatment. Patients with elevations in HIV-1 RNA on DRV/r
      monotherapy could be re-intensified with NRTIs. The trial had 80% power to show
      non-inferiority for the monotherapy arm (delta = - 12%). RESULTS: Patients were
      83% male and 87% Caucasian, with mean age 42 years; 10% were HCV antibody
      positive. In the DRV/r monotherapy arm, there were more patients with nadir CD4
      count below 200 cells/uL (30% versus 22%). In the primary efficacy analysis, HIV
      1 RNA <50 copies/mL by Week 48 (intent-to-treat (ITT)) was 118/137 (86.1%) in the
      DRV/r monotherapy arm versus 129/136 (94.9%) in the triple therapy arm; DRV/r
      monotherapy did not show non-inferiority versus triple therapy in the primary
      analysis (difference=- 8.7%, 95% CI -15.5 to -1.8%). In the multivariate
      analysis, the main predictor of treatment failure was nadir CD4 count. For
      patients with nadir CD4 counts <200 cells/uL, HIV-1 RNA suppression rates at Week
      48 were 27/41 (66%) in the DRV/r monotherapy arm and 29/30 (97%) in the triple
      therapy arm; for patients with CD4 nadir at least 200 cells/uL, HIV-1 RNA
      suppression rates were 91/96 (95%) in the DRV/r monotherapy arm and 100/106 (94%)
      in the triple therapy arm. In the overall population, by a switch included
      analysis, efficacy was 92.0% versus 96.3%, showing non-inferiority (difference=-
      4.3%, 95% CI=-9.7 to +1.2%). No treatment-emergent primary PI mutations were
      detected in three patients with sustained elevations in HIV-1 RNA at least 400
      copies/mL (two on PI monotherapy, one on triple therapy). CD4 counts remained
      stable during the trial in both arms. CONCLUSIONS: In this study for patients
      with HIV-1 RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy showed
      lower efficacy versus triple antiretroviral therapy at Week 48 in the primary
      switch equals failure analysis (86% versus 95%). However, this lower efficacy was
      seen mainly in patients with CD4 nadir levels below 200 cells/uL. There was no
      development of PI resistance.

PMID- 25394035
TI  - Analysis of neurocognitive function and CNS endpoints in the PROTEA trial:
      darunavir/ritonavir with or without nucleoside analogues.
AB  - INTRODUCTION: During treatment with protease inhibitor monotherapy, the number of
      antiretrovirals with therapeutic concentrations in the cerebrospinal fluid (CSF)
      is lower, compared to standard triple therapy. However, the clinical consequences
      are unclear. METHODS: A total of 273 patients with HIV RNA <50 copies/mL for over
      24 weeks on current antiretrovirals randomized to darunavir/ritonavir (DRV/r)
      800/100 mg once-daily, either as monotherapy (n=137) or with 2NRTIs (n=136).
      Neurocognitive function was evaluated in all patients by the Hopkins Verbal
      Learning Tests, the Colour Trail Tests and the Grooved Pegboard Test at
      screening, baseline and at Week 48. A global neurocognitive score (NPZ-5) was
      derived by averaging the standardized results of the five domains. In a central
      nervous system (CNS) sub-study (n=70), HIV RNA levels in the CNS were evaluated
      at baseline and Week 48. Clinical adverse events related to the CNS were
      collected at each visit. RESULTS: Patients were 83% male and 88% White, with
      median age 43 years. There were more patients with nadir CD4 count below 200
      cells/uL in the DRV/r monotherapy arm (41/137, 30%) than the triple therapy arm
      (30/136, 22%). At Week 48, there was no difference between the treatment arms for
      the five combined domains of the neurocognitive score. At Week 48, the percentage
      of patients with an abnormal neurocognitive score among the five domains was
      12.2% for DRV/r monotherapy and 14.9% for triple therapy. However, one patient on
      DRV/r monotherapy with a CD4 nadir of 17 cells/uL was hospitalized with HIV
      encephalomyelitis at Week 24, with HIV RNA 2500 copies/mL in the CSF and 125
      copies/mL in the plasma. Symptoms resolved after intensification with high dose
      zidovudine. A second patient on DRV/r monotherapy with CD4 nadir of 166 cells/uL
      had a rise in HIV RNA in CSF from <40 copies/mL at baseline to 654 copies/mL at
      Week 48, with concurrent plasma HIV RNA of 77 copies/mL. CONCLUSIONS: In this
      study for patients with HIV RNA <50 copies/mL at baseline, there was no
      difference in neurocognitive function between the treatment arms. However two
      patients on PI monotherapy with CD4 nadir <200 cells/uL developed viraemia in
      both CSF and plasma, with one symptomatic case. DRV/r monotherapy should be used
      with caution in patients with nadir CD4 counts below 200 cells/uL.

PMID- 25394036
TI  - Rate of viral load failure over time in people on ART in the UK Collaborative HIV
      Cohort (CHIC) study.
AB  - INTRODUCTION: Most people achieve and maintain viral load (VL) suppression on
      first-line antiretroviral therapy (ART) but for a minority this does not happen.
      It is unclear whether those who have maintained VL suppression for several years
      will be able to continue to do so, or if rates of VL failure - due to poor
      adherence, ART interruption and/or resistance - remain at appreciable levels.
      METHODS: Eligible participants were ART-naive and started treatment after 1st
      January 2000, with >=3 antiretrovirals and >=9 months follow-up. VL failure was
      defined as failure to achieve VL suppression (<=50 copies/mL) by 9 months on ART
      or a single VL >200 copies/mL after 9 months after start of ART. Kaplan-Meier
      estimates were used to examine the cumulative probability of experiencing a VL
      >200 copies/mL over time, irrespective of treatment interruption (Figure 1).
      Follow-up was censored at last VL assessment but not at treatment interruption.
      In a sensitivity analysis, VL failure was instead defined as two consecutive VL
      >1000 copies/mL. RESULTS: A total of 13,556 participants were included. Median
      (IQR) age at start of ART was 37 (32-43), median follow-up 4.1 (2.3-6.7) years,
      pre-ART VL 71,400 (17,400-221,900) copies/mL and pre-ART CD4 count 204 (110-290)
      cells/mm(3). Fifty-one percent were white, 71% male and 50% MSM. Of which, 5,351
      (39%) participants experienced a VL >200 copies/mL. In sub-groups of participants
      the proportion experiencing a VL >200 copies/mL by one year after start of ART
      were: <50 years 22%, >=50 years 17%, men 20%, women 26%, MSM 19%, black
      heterosexuals 23%, white heterosexuals 26% and other 23%. The median time to VL
      >200 copies/ml was 8 years. In sensitivity analyses based on 12,811 participants,
      4274 (33%) experienced two consecutive VL >1000 copies/mL. Table 1 presents the
      rate of experiencing a VL >200 copies/mL (two consecutive VL >1000 copies/mL) by
      time since start of ART. The rate of VL >200 copies/mL declines over time, from
      30 per 100 person-years after up to two years after ART, to two per 100 person
      years after up to 11.5 years after ART. A sum of 2,047 (15%) participants stopped
      ART at some point (10, 14 and 17% had stopped ART by 1, 3, and 5 years,
      respectively). CONCLUSIONS: Although resistance will often not be present and,
      even if present, several drug options will likely remain, first occurrence of VL
      > 200 copies/mL after having attained viral suppression continues to occur after
      10 years on ART.

PMID- 25394037
TI  - HIV treatment 2020: what will it look like?
AB  - Currently there are 28 approved antiretroviral drugs in six mechanistic classes,
      and recommended first-line regimens are highly potent, well tolerated, and as
      convenient as one pill, once-a-day. How will HIV treatment change by 2020? Over
      the next few years, we are likely to see potent 2-drug regimens tested head-to
      head with standard three-drug regimens, and some of these will likely become
      standard-of-care. Newer agents with novel drug resistance profiles (e.g.
      doravirine, an NNRTI) or new mechanisms of action (e.g. BMS 663068, a CD4
      attachment inhibitor) will provide virologic activity in patients with drug
      resistant viral strains. Comparative studies of current and newer agents such as
      the investigational prodrug of tenofovir (TAF) will help define less toxic
      regimens. We will see additional convenient co-formulations developed; with them,
      we are likely to have second- and even third-line regimens administered one pill,
      once-daily. Long-acting injectable investigational formulations currently in
      clinical trials such as rilpivirine LA (administered monthly) and cabotegravir
      (administered quarterly), and others (including combinations of these agents)
      could provide additional convenient treatment options. Other novel formulations
      (e.g. patches, implants, rings) and combinations of antiretrovirals with other
      kinds of medications (e.g. contraceptives) may be developed and tested. In the
      developing world, we will see increasing numbers of patients taking potent, well
      tolerated convenient first-line and subsequent regimens with the goal of "20 by
      20" - 20 million treated people by 2020. Generic formulations of antiretroviral
      drugs, including combinations, will be increasingly available and used worldwide.
      With the current appreciation that inflammation and immune activation play an
      important role in the natural history of treated HIV infection, anti-inflammatory
      agents will be tested and may supplement (or even be co-formulated with) standard
      antiretroviral regimens. Recognizing our progress to date, these and other
      innovations will further improve HIV therapy by 2020. 

PMID- 25394038
TI  - HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced
      subjects: week 24 sub-group analysis.
AB  - INTRODUCTION: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that
      binds directly to HIV-1 gp120, preventing initial viral attachment and entry into
      the host CD4+ T-cell. AI438011 is a Phase IIb, randomized, active-controlled
      trial investigating the safety, efficacy and dose-response of BMS-663068 versus
      atazanavir/ritonavir (ATV/r) in treatment-experienced (TE), HIV-1-positive
      subjects. MATERIALS AND METHODS: Antiretroviral TE subjects (exposure to >=1
      antiretroviral for >=1 week) with susceptibility to all study drugs (BMS-626529
      IC50 100 nM), were randomized equally to four BMS-663068 arms (400 or 800 mg,
      BID; 600 or 1200 mg, QD) and a control group (ATV/r 300/100 mg QD) with tenofovir
      disoproxil fumarate (TDF) + raltegravir (RAL). A sub-group analysis of viral
      efficacy and immunologic reconstitution is presented. RESULTS: A total of 251
      subjects were treated. Median age was 39 years, 60% were male and 38% were white.
      Median baseline (BL) viral load (VL) was 4.85 log10 c/mL (43%; 100,000 c/mL) and
      median CD4+ T-cell count was 230 cells/mm(3) (38%; 200 CD4 cells/mm(3)). Through
      Week 24, response rates (HIV-1 RNA 50 c/mL) were comparable across all BMS-663068
      arms and the ATV/r arm regardless of gender, age and race. Response rates for
      subjects with BL VL 100,000 c/mL (BMS-663068, 82-96%; ATV/r, 93%) were higher
      than those for subjects with BL VL >=100,000 c/mL (BMS-663068, 70-87%; ATV/r,
      73%); however, there were no substantial differences in response across the BMS
      663068 and ATV/r arms in either sub-group. Response rates for subjects with BL
      CD4+ cell counts >=200 cells/mm(3) (87-96%) were higher than those for subjects
      with BL CD4+ cell counts 200 cells/mm(3) (62-82%); however, no substantial
      differences in response were seen across the BMS-663068 and ATV/r arms in either
      sub-group. Mean changes in CD4+ T-cell counts from BL were similar across all
      arms regardless of gender, age and BL CD4+ T-cell count. CONCLUSION: Virologic
      response rates were similar across the BMS-663068 and ATV/r arms in TE subjects,
      regardless of BL demographic characteristics (gender, race, age), BL HIV-1 RNA,
      or BL CD4+ T-cell count. Mean increases in CD4+ T-cell counts across the BMS
      663068 arms were consistent with ATV/r, regardless of gender, age and BL CD4+ T
      cell count. These results support continued development of BMS-663068. Note:
      Previously submitted at IDWeek, Philadelphia, PA, 8 October 2014.

PMID- 25394039
TI  - Safety profile of HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral
      experienced subjects: week 24 analysis.
AB  - INTRODUCTION: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that
      binds directly to HIV-1 gp120, preventing initial viral attachment and entry into
      the host CD4+ T-cell. AI438011 is an ongoing, Phase IIb, randomized, active
      controlled trial investigating the safety, efficacy and dose-response of BMS
      663068 vs. atazanavir/ritonavir (ATV/r) in treatment-experienced (TE), HIV-1
      positive subjects. At Week 24, response rates across the BMS-663068 arms were
      consistent with ATV/r. MATERIALS AND METHODS: Antiretroviral TE subjects
      (exposure to >=1 antiretroviral for >=1 week) with susceptibility to all study
      drugs (including BMS-626529 IC50 100 nM) were randomized equally to four BMS
      663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control arm (ATV/r
      300/100 mg QD), with tenofovir disoproxil fumarate (TDF) + raltegravir (RAL). The
      complete safety profile through Week 24 is reported. RESULTS: In total, 251
      subjects were treated (BMS-663068, 200; ATV/r, 51). No BMS-663068-related adverse
      events (AEs) led to discontinuation. Grade 2-4 drug-related AEs occurred in
      17/200 (8.5%) subjects across the BMS-633068 arms; however, these events were
      mostly single instances and no dose-relationship was seen. Similarly, no
      noticeable trend for Grade 3-4 laboratory abnormalities was seen and Grade 3-4
      hematologic changes and liver chemistry elevations were uncommon (neutropenia,
      2.5%; AST/ALT elevations, 1% (n=196)). In the ATV/r arm, Grade 2-4 drug-related
      AEs occurred in 14/51 (27.5%) subjects and were mostly secondary to
      gastrointestinal and/or hepatobiliary disorders. Serious adverse events (SAEs)
      occurred in 13/200 (6.5%) and 5/51 (9.8%) subjects receiving BMS-663068 and
      ATV/r, respectively; most were secondary to infections and none were related to
      study drugs. The most common AE reported for BMS-663068 was headache (28/200,
      14%), occurring in 5/51 (10%) subjects in the ATV/r arm; in the BMS-663068 arms,
      this was not dose-related. There were no deaths. CONCLUSIONS: BMS-663068 was
      generally well tolerated across all arms, with no related SAEs or AEs leading to
      discontinuation and no dose-related safety signals. There were no trends for
      Grade 2-4 AEs or clinical laboratory abnormalities. These results support
      continued development of BMS-663068. Note: Previously submitted at IDWeek,
      Philadelphia, PA, 8 October 2014.

PMID- 25394040
TI  - Cenicriviroc blocks HIV entry but does not lead to redistribution of HIV into
      extracellular space like maraviroc.
AB  - INTRODUCTION: Cenicriviroc (CVC), a once-daily, dual CCR5/CCR2 co-receptor
      antagonist, has completed Phase 2b development. CVC demonstrated favourable
      safety and similar efficacy compared with efavirenz (EFV) in Study 202
      (NCT01338883); an ex vivo sub-analysis evaluated treatment effects on HIV entry,
      measured by intracellular HIV DNA declines, in subjects with virologic success at
      Week 24. In addition, in vitro assays determined and compared the extent of any
      cell-free virion redistribution that CVC or maraviroc (MVC) may cause. METHODS:
      Ex vivo: intracellular DNA (frozen PBMCs) from 30 subjects with virologic success
      at Week 24 (10, 13 and 7 subjects on CVC 100 mg, CVC 200 mg and EFV,
      respectively). Early (strong-stop) and late (full-length) reverse transcript
      levels were measured by qPCR. In vitro: PM-1 cells were infected with CCR5-tropic
      HIV-1 BaL in the presence or absence of inhibitory concentrations of CVC (20 nM),
      MVC (50 nM) or controls. P24 and viral load levels were measured by ELISA and qRT
      PCR after 4 hours. RESULTS: Ex vivo analysis showed full-length HIV DNA declines
      were similar across all groups (CVC 100 mg, CVC 200 mg and EFV) at Week 24.
      Strong-stop HIV DNA declines (a marker of HIV entry) at Week 24 were pronounced
      for both CVC arms (CVC 100 mg, 51% decline; CVC 200 mg, 37% decline) compared to
      no decline for the EFV arm. In vitro experiments revealed that CVC-treated cells
      had lower levels of supernatant P24 at 4 hours versus baseline (0 hrs: 506 ng/mL;
      4 hrs: 192 ng/mL), but P24 levels remained constant for MVC-treated cells after 4
      hours (0 hrs: 506 ng/mL; 4 hrs: 520 ng/mL). Viral load levels for CVC-treated
      cells remained stable after 4 hours (0 hrs: 1.19*10(10) copies/mL; 4 hrs:
      1.26*10(10) copies/mL). MVC-treated cells exhibited a slight increase in viral
      load after 4 hours (0 hrs: 1.19*10(10) copies/mL; 4 hrs: 1.67*10(10) copies/mL).
      CONCLUSIONS: Ex vivo analysis confirmed that CVC treatment blocks HIV entry
      (strong-stop HIV DNA declines), while in vitro analysis showed that CVC-treated
      cells do not repel virus back into the extracellular space, as seen with MVC.
      Experiments are underway to determine whether or not interactions between CVC and
      HIV at the binding site may explain these unanticipated findings.

PMID- 25394041
TI  - Forty-eight-week efficacy and safety and early CNS tolerability of doravirine (MK
      1439), a novel NNRTI, with TDF/FTC in ART-naive HIV-positive patients.
AB  - INTRODUCTION: Doravirine (DOR) is an investigational NNRTI (aka MK-1439) that
      retains activity against common NNRTI-resistant mutants. We have previously
      reported the Part 1 results from a two-part, randomized, double-blind, Phase IIb
      study in ART-naive HIV-1-positive patients (1). At doses of 25, 50, 100 and 200
      mg qd, DOR plus open-label tenofovir/emtricitabine (TDF/FTC) demonstrated potent
      antiretroviral activity comparable to EFV 600 mg qhs plus TDF/FTC and was
      generally well tolerated at week 24. DOR 100 mg was selected for use in patients
      continuing in Part 1 and those newly enrolled in Part 2. METHODS: Patients
      receiving DOR 25, 50 or 200 mg in Part 1 were switched to 100 mg after dose
      selection. In Part 2, 132 additional patients were randomized 1:1 to DOR 100 mg
      qd or EFV 600 mg qhs (each with TDF/FTC). We present week 48 efficacy and safety
      results for all patients in Part 1, and early (week 8) CNS tolerability only for
      patients randomized to DOR 100 mg or to EFV in Parts 1 and 2 combined. The
      primary safety endpoint is the % of patients with pre-specified CNS events (all
      causality) by week 8 for DOR 100 mg qd vs EFV (Parts 1 + 2 combined). RESULTS:
      Part 1 week 48 efficacy and safety results are shown below. CONCLUSIONS: In ART
      naive, HIV-1-positive patients also receiving TDF/FTC, DOR 100 mg qd demonstrated
      potent antiretroviral activity and immunological effect at week 48 and was
      generally safe and well tolerated. Patients who received DOR 100 mg qd had
      significantly fewer treatment-emergent CNS AEs by week 8 than those who received
      EFV.

PMID- 25394042
TI  - Socio-economic factors and virological suppression among people diagnosed with
      HIV in the United Kingdom: results from the ASTRA study.
AB  - INTRODUCTION: In the United Kingdom, rates of virological suppression on
      antiretroviral therapy (ART) are very high, but there remain a small but
      significant number of people on ART with detectable viraemia. The impact of socio
      economic factors on virological suppression has been little studied. MATERIALS
      AND METHODS: We used data from ASTRA, a cross-sectional, questionnaire study of
      >3000 individuals from 8 clinics in the United Kingdom in 2011-2012, linked to
      clinical records to address this question. Included participants had received ART
      for >6 months with a recorded current viral load (VL) (latest at the time of
      questionnaire). Participants provided data on demographic factors: gender, sexual
      orientation, ethnicity and age; and socio-economic factors: UK birth/English
      reading ability, employment, housing, education and financial hardship. To assess
      non-adherence, participants were asked if in the past 3 months, they had missed
      ART for >=2 days at a time. Virological suppression was defined as VL<=50 cps/mL.
      For each socio-economic factor, we calculated prevalence ratios using modified
      Poisson regression, first adjusting for demographic factors, then also for non
      adherence. RESULTS: A total of 2445 people fulfilled the inclusion criteria (80%
      male, 69% MSM, median age: 46 years, median CD4 count: 556 cells/mm(3)); 10%
      (234/2445) had VL>50 cps/mL. After adjusting for demographic factors, non-fluent
      English, not being employed, not home owning, education below university level
      and increasing financial hardship were each associated with higher prevalence of
      VL>50 cps/mL. Additional adjustment for non-adherence largely attenuated each
      association, but did not fully explain them (see Table 1). After adjustment for
      non-adherence and demographic factors, younger age was also associated with VL>50
      cps/mL: for each additional 10 years an individual was 0.80 (95% CI 0.70-0.92)
      times as likely to have VL>50 cps/mL (p=0.0019). Adjusted prevalence ratios for
      VL>50cps/mL were 0.91 (0.62-1.34) for women and 1.25 (0.85-1.84) for non-MSM men
      versus MSM, and 1.29 (0.92-1.80) for white versus non-white people. CONCLUSIONS:
      Among people on ART in the United Kingdom, the proportion with detectable VL is
      low. Poorer socio-economic status is associated with increased probability of
      virological non-suppression. It is likely that much of this association is
      mediated through difficulties in taking ART. Emphasis should be put on aiding the
      adherence of people in these higher risk groups.

PMID- 25394043
TI  - Factors associated with the continuum of care of HIV-infected patients in
      Belgium.
AB  - INTRODUCTION: We studied factors associated with the continuum of HIV care in
      Belgium. METHODS: Data of the national registration of new HIV diagnosis and of
      the national cohort of HIV-infected patients in care were combined to obtain
      estimates of and factors related with proportions of HIV-infected patients in
      each step of the continuum of care from diagnosis to suppressed viral load (VL).
      Factors associated with ignorance of HIV seropositivity were analyzed among
      patients co-infected with HIV and STI in the Belgian STI sentinel surveillance
      network. Associated factors were identified by multivariate logistic regression.
      RESULTS: Among 4038 individuals diagnosed with HIV between 2007 and 2010, 90.3%
      were linked to care. Of 11684 patients in care in 2010, 90.8% were retained in
      care up to the following year, 88.3% of those were on ART, of whom 95.3% had
      suppressed VL (<500 cp/ml) (Figure 1). In multivariate analyses, factors
      associated with ignoring HIV+ status were being younger (p<0.001), being
      heterosexual compared to MSM, and of a region of origin other than Belgium, Sub
      Saharan Africa and Europe. Non-Belgian regions of origin were associated with
      lower entry and retention in care (p<0.001 for both). Preoperative HIV testing
      was associated with lower entry in care (p=0.003). MSM had a higher retention in
      care (p<0.001), whilst IDU had lower retention (p=0.004). Low CD4 at first
      clinical contact and clinical reasons for HIV testing were independently
      associated with being on ART (p<0.001 for both); whilst prenatal HIV diagnosis
      was associated with lower proportion on ART (p=0.016) and lower proportion with
      suppressed VL among those on ART (p=0.005). Older age was associated with both
      being on ART and having suppressed VL among those on ART (p=0.007 and p<0.001
      respectively), independently of time since HIV diagnosis (Table 1). CONCLUSIONS:
      Regions of origin and risk groups (MSM/heterosexual/IDU) are the main factors
      associated with ignorance of HIV seropositivity, entry and retention in care, but
      once the HIV patient is retained in care, no effect of these factors on the
      proportions on ART and with suppressed VL are observed. The association of
      prenatal HIV diagnosis and proportions on ART and with suppressed VL could be
      biased by transitory CD4 disturbances during pregnancy and ART discontinuation
      after pregnancy. The higher probabilities of older patients to be on ART and have
      suppressed VL once retained in care could be influenced by factors not studied
      here like comorbidities, adherence or duration on ART.

PMID- 25394044
TI  - Loss to follow-up of HIV-infected women after delivery: The Swiss HIV Cohort
      Study and the Swiss Mother and Child HIV Cohort Study.
AB  - INTRODUCTION: HIV-infected pregnant women are very likely to engage in HIV
      medical care to prevent transmission of HIV to their newborn. After delivery,
      however, childcare and competing commitments might lead to disengagement from HIV
      care. The aim of this study was to quantify loss to follow-up (LTFU) from HIV
      care after delivery and to identify risk factors for LTFU. METHODS: We used data
      on 719 pregnancies within the Swiss HIV Cohort Study from 1996 to 2012 and with
      information on follow-up visits available. Two LTFU events were defined: no
      clinical visit for >180 days and no visit for >360 days in the year after
      delivery. Logistic regression analysis was used to identify risk factors for a
      LTFU event after delivery. RESULTS: Median maternal age at delivery was 32 years
      (IQR 28-36), 357 (49%) women were black, 280 (39%) white, 56 (8%) Asian and 4%
      other ethnicities. One hundred and seven (15%) women reported any history of IDU.
      The majority (524, 73%) of women received their HIV diagnosis before pregnancy,
      most of those (413, 79%) had lived with diagnosed HIV longer than three years and
      two-thirds (342, 65%) were already on antiretroviral therapy (ART) at time of
      conception. Of the 181 women diagnosed during pregnancy by a screening test, 80
      (44%) were diagnosed in the first trimester, 67 (37%) in the second and 34 (19%)
      in the third trimester. Of 357 (69%) women who had been seen in HIV medical care
      during three months before conception, 93% achieved an undetectable HIV viral
      load (VL) at delivery. Of 62 (12%) women with the last medical visit more than
      six months before conception, only 72% achieved an undetectable VL (p=0.001).
      Overall, 247 (34%) women were LTFU over 180 days in the year after delivery and
      86 (12%) women were LTFU over 360 days with 43 (50%) of those women returning.
      Being LTFU for 180 days was significantly associated with history of intravenous
      drug use (aOR 1.73, 95% CI 1.09-2.77, p=0.021) and not achieving an undetectable
      VL at delivery (aOR 1.79, 95% CI 1.03-3.11, p=0.040) after adjusting for maternal
      age, ethnicity, time of HIV diagnosis and being on ART at conception.
      CONCLUSIONS: Women with a history of IDU and women with a detectable VL at
      delivery were more likely to be LTFU after delivery. This is of concern regarding
      their own health, as well as risk for sexual partners and subsequent pregnancies.
      Further strategies should be developed to enhance retention in medical care
      beyond pregnancy.

PMID- 25394045
TI  - Patients' willingness to take separate component antiretroviral therapy regimens
      for HIV in the Netherlands.
AB  - INTRODUCTION: The costs of combination antiretroviral therapy (cART) consisting
      of separate, particularly generic, components are generally much lower than of a
      single tablet regimen (STR) including the same active ingredients. Our aim was to
      evaluate whether patients in care in the Netherlands would be willing to take
      separate component regimens (SCR) instead of an STR and to examine whether
      willingness was associated with particular patient characteristics. MATERIALS AND
      METHODS: Data from the HIV Monitoring Foundation of all adult HIV-1-infected
      patients in care taking cART>6 months were used to randomly select 1000 patients.
      As part of a questionnaire developed for a study assessing patient experience,
      patients were asked whether they were willing to take an SCR instead of an STR.
      Logistic regression was used to examine associations between age, gender, region
      of origin, mode of HIV transmission, socioeconomic status, duration of cART and
      answering "yes" to the question versus "maybe" or "no." Variables with p<0.1 in
      the univariate analysis were entered in a multivariate model. RESULTS: Of the 300
      patients who completed the questionnaire, 49% answered "yes," 24% "maybe" and 27%
      "no" to the question whether they would be willing to use a SCR. Reasons for
      answering "no" included difficulties swallowing pills, convenience of STR
      (especially when travelling/at work), and concerns about side effects.
      Respondents who answered "maybe" often indicated that they preferred STRs,
      emphasized the importance of taking the pills once daily, and pointed out that
      efficacy/safety of an SCR should not be less. Having to pay for medication was
      reported as a reason to consider switching to an SCR. In the multivariate
      analysis, respondents who were born outside the Netherlands were less likely; and
      those with cART use >=15 yrs were more likely to answer "yes" (Table 1).
      CONCLUSIONS: Half of the respondents were willing to take SCRs instead of an STR.
      The likelihood of accepting to switch to SCR seems less for migrants and for
      those who have commenced treatment more recently. Duration of cART use and region
      of origin may therefore be factors to take into account when considering to
      prescribe SCR. Future studies should investigate whether an expressed willingness
      to switch will translate into maintained high levels of adherence and viral
      suppression.

PMID- 25394046
TI  - Real-world medication persistence with single versus multiple tablet regimens for
      HIV-1 treatment.
AB  - INTRODUCTION: Adherence to antiretroviral (ARV) treatment for HIV-1 is crucial to
      achieving optimal clinical outcomes. Simplification of regimens with once-daily
      single-tablet regimens (STRs) can improve adherence compared to multi-tablet
      regimens (MTRs). This study compared real-world persistence (a proxy for
      treatment effectiveness and adherence) between HIV-1 infected patients receiving
      STRs versus MTRs. MATERIALS AND METHODS: Adult HIV-1 infected patients starting
      their first observed ARV regimen (with at least six prior months of no ARV
      treatment) were identified in the MarketScan claims database (10/2008-03/2014).
      Persistence was measured as the time from the index regimen start date to the end
      of the first 90-day gap between fills for any ARV in the index regimen, or to the
      start date of an ARV not in the index regimen. Persistence was described using
      Kaplan-Meier curves and compared using log-rank tests, and Cox proportional
      hazards models adjusted for age, gender, insurance type, region, employment
      status, Charlson Comorbidity Index, other comorbidities, hospitalizations,
      emergency room visits and office visits. STRs were further stratified by regimen.
      RESULTS: A total of 3257 patients (37%) initiated MTRs, and 5484 (63%) initiated
      STRs, including 4409 on efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC), 484
      on rilpivirine (RPV)/TDF/FTC, and 591 on elvitegravir (EVG)/cobicistat
      (COBI)/TDF/FTC. Median persistence was 45.0 months for STRs versus 15.2 months
      for MTRs (P<0.001; Figure 1). Median persistence was not reached for RPV/TDF/FTC
      or EVG/COBI/TDF/FTC; 31 months after RPV/TDF/FTC approval for the treatment of
      HIV-1 infection, more than 65% of patients who started on it remained persistent,
      and 19 months after EVG/COBI/TDF/FTC approval, more than 72% of patients who
      started on it remained persistent. Compared with MTRs, STRs had an approximately
      50% lower hazard of discontinuation (adjusted hazard ratio [HR]=0.54, 95% CI 0.50
      0.58). EVG/COBI/TDF/FTC and RPV/TDF/FTC had significantly longer unadjusted and
      adjusted persistence compared with EFV/TDF/FTC (Figure 2, Table 1). CONCLUSIONS:
      Among HIV-1 infected patients, the use of STRs was associated with longer regimen
      persistence compared with MTRs. Among STRs, EVG/COBI/TDF/FTC and RPV/TDF/FTC were
      associated with significantly longer persistence than EFV/TDF/FTC.

PMID- 25394047
TI  - No difference in persistence to treatment with atazanavir or darunavir in HIV
      patients in a real-world setting.
AB  - INTRODUCTION: There is a lack of data comparing the protease inhibitors (PIs)
      atazanavir (ATV) and darunavir (DRV) in a real-world setting. This study compared
      persistence (time to switch/discontinuation) to therapy between ATV-treated and
      DRV-treated patients with human immunodeficiency virus (HIV). MATERIALS AND
      METHODS: Retrospective, observational cohort study using US insurance claims for
      commercially and Medicaid-insured patients. Patients were aged >=18 years and
      initiated an ATV- or DRV-based regimen boosted with ritonavir between 7/1/2006
      and 3/31/2013, with >=6 months of continuous enrolment prior to and >=3 months of
      continuous enrolment following initiation; patients were required to have >=1
      inpatient or outpatient medical claim with an ICD-9-CM diagnosis code for HIV
      during that time period of enrolment. Patients with no claims for antiretroviral
      therapy (ART) any time prior to initiation were considered to be ART-naive. Time
      to switch/discontinuation was defined as the number of days from initiation of
      the regimen until earliest of: (1) a >=30-day continuous gap in therapy in ATV or
      DRV; (2) a prescription claim for an ART agent that was not part of the initial
      regimen (with the exception of changes in concomitant nucleoside reverse
      transcriptase inhibitors or the addition of integrase inhibitors); (3) censoring
      at a >=30-day continuous gap in therapy in ritonavir; (4) censoring at
      disenrolment from insurance benefits or (5) censoring at the study end date
      (9/30/2013 in the commercial data and 12/31/2013 in the Medicaid data). Time to
      switch/discontinuation was compared using incidence rates and multivariable Cox
      proportional hazards models adjusted for calendar time, patient demographics and
      clinical characteristics. RESULTS: Table 1 displays the study results and cohort
      sample sizes. Mean ages across the cohorts were 41-42 years. The proportions of
      patients who were ART-naive were 58-59% among the ATV/r cohorts and 53-55% among
      the DRV/r cohorts. There were no significant differences in the adjusted hazards
      of switch/discontinuation between the cohorts. CONCLUSIONS: The incidence of
      switch/discontinuation was higher among Medicaid patients (who may be
      socioeconomically disadvantaged) than Commercial patients. There were no
      significant differences in persistence (time to switch/discontinuation) with the
      initiated PI among HIV patients who initiated an ATV-based regimen versus a DRV
      based regimen.

PMID- 25394048
TI  - Patient preferences for characteristics of antiretroviral therapies: results from
      five European countries.
AB  - INTRODUCTION: Patient preference to antiretroviral therapy (ART) characteristics
      should be a key consideration in treatment decisions. ART options exist for
      people living with HIV (PLWH), however concerns remain related to PLWH
      satisfaction with current ARTs. The current study examines patient preferences
      and the strength of preferences for treatment characteristics associated with
      ART. MATERIALS AND METHODS: Patients' preferences to ART were explored using a
      discrete choice experiment (DCE). Seven defined treatment characteristics (each
      with three categories) were identified from a literature review, input from
      experts, PLWH and physicians. A total of 1582 PLWH from France, Germany, Spain,
      Italy and the UK were recruited for the study. An adjusted odds ratio <1
      signified lower odds of selecting a treatment with this characteristic category,
      compared to the reference category, independently of other characteristics.
      RESULTS: The patient preference analyses showed that participants preferred
      treatments with a rapid reduction in viral load (OR=0.78; 95% CI 0.74-0.81) and
      CD4 count (OR=0.86; 95% CI=0.82-0.89). Participants had a strong preference for
      avoiding diarrhoea (Odds ratio, OR=0.36 95% CI=0.33-0.38) and long term health
      problems (OR=0.30, 95% CI=0.28-0.32). Convenience related issues related to
      restrictions on taking drugs because of food or drug interactions were important
      to avoid (OR=0.80, 95% CI=0.76-0.83 and OR=0.72 95% CI=0.69-0.76 respectively).
      Participants also had a strong preference to avoid drugs which limited the
      effectiveness of future treatments (OR=0.70, 95% CI=0.67-0.73). CONCLUSIONS:
      Avoidance of diarrhoea and long-term complications were the most important
      drivers of patient choice. This study, from a large sample of European patients,
      demonstrates the importance to patients when different aspects of HIV treatment
      are considered simultaneously.

PMID- 25394049
TI  - Cerebrospinal-fluid exposure of efavirenz and its major metabolites when dosed at
      400 and 600 mg once daily; a randomized controlled trial.
AB  - INTRODUCTION: The optimal penetration of antiretroviral agents into central
      nervous system (CNS) may be a balance between providing adequate drug exposure to
      inhibit HIV-replication whilst avoiding concentrations associated with
      toxicities. METHODS: Cerebrospinal-fluid (CSF) exposure of efavirenz and
      metabolites 7-hydroxy (7OH-) and 8OH-efavirenz were assessed after at least 12
      weeks of antiretroviral therapy in HIV-infected subjects randomized to commence
      antiretroviral regimens containing efavirenz at either 400 mg or 600 mg once
      daily. Clinical, pharmacokinetic and pharmacogenomic factors associated with CSF
      efavirenz and its metabolite concentrations were assessed. RESULTS: Of 28
      subjects who completed all study procedures (14/14 on efavirenz 400 mg/600 mg),
      CSF HIV RNA was below 20 copies/mL in all at the time of examination.
      Concentrations of efavirenz and 7OH-efavirenz in the CSF were slightly lower when
      dosed at 400 mg versus 600 mg, although this was not statistically significant. A
      different trend was observed regarding 8OH-efavirenz concentrations where CSF
      exposure was slightly increased in the 400 mg efavirenz arm (see Table 1).
      Efavirenz concentration in the CSF was above 0.51 ng/mL (proposed CSF IC50 for WT
      virus) in all subjects and 8OH-efavirenz concentration in the CSF was above 3.3
      ng/mL (a proposed toxicity threshold, reference) in 11/14 and 7/14 subjects
      randomized to the 400 mg and 600 mg doses of efavirenz, respectively. Whilst CSF
      efavirenz concentration was significantly associated with plasma concentration
      (P<0.001) and CYP2B6 genotype (CSF efavirenz GG to GT/TT GM ratio 0.56, 90% CI
      0.42-0.74), CSF 8OH-efavirenz concentration was not (P=0.242 for association with
      plasma concentration and CSF 8OH-efavirenz GG to GT/TT GM ratio 1.52, 90% CI 0.97
      2.36). Lastly, CSF 8OH-efavirenz concentration was associated with efavirenz
      symptom questionnaire results at one year (Spearman's correlation 0.13, P=0.05).
      CONCLUSIONS: With both doses of efavirenz studied, CSF concentrations were
      considered adequate to inhibit HIV-replication, although concentrations of 8OH
      efavirenz were greater than that reportedly associated with neuronal toxicity.
      CSF exposure of 8OH-efavirenz was not dependent on plasma exposure and we
      postulate may be subject to saturable pharmacokinetic effects.

PMID- 25394050
TI  - Rates of cardiovascular events and deaths are associated with advanced stages of
      HIV-infection: results of the HIV HEART study 7, 5 year follow-up.
AB  - INTRODUCTION: Cardiovascular diseases are increasing in aging HIV-positive
      patients (HIV+). Impact of traditional cardiovascular risk factors, HIV-specific
      parameters and antiretroviral therapy (ART) on the incidence of cardiovascular
      events (CVE) and on the mortality rate are investigated in different HIV+
      cohorts. METHODS: The HIV HEART (HIVH) study is an ongoing prospective
      observational cohort study in the German Ruhr area to assess the frequency and
      clinical course of cardiac disorders in 1481 HIV+ by standardized non-invasive
      cardiovascular screening. CVE were defined as diagnosed or documented myocardial
      infarction, coronary heart disease, arterial coronary intervention, stent
      implantation, bypass operation and stroke. RESULTS: 1481 HIV+ subjects (mean age:
      49.3+/-10.7 years (y), female: 15.6%) were included. 130 CVE and 90 deaths were
      documented until the end of 7, 5 year follow-up of HIVH. Mean duration of the HIV
      infection was 12.9+/-6.8 y. HIV+ were treated with ART on average for 8.6+/-6.8
      y. According to the CDC classification of the HIV-infection, HIV+ were
      distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9%) while
      more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%;
      III:50.7%). Advanced clinical and immunological stages were significantly
      (p<0.001) associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7%
      and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%;
      II:32.3%; III:64.6%) but not with the duration of HIV-infection (per y: Hazard
      ratio (HR): 0.91 [0.88-0.94]) and ART (per y: HR: 0.81 [0.79-0.84]) adjusted for
      age. The proportion of deceased HIV+ with HIV-RNA >=50 copies/mL and lower CD4
      cell counts at their last visit is significantly higher compared with living HIV+
      without CVE (HIV-RNA >=50 copies/mL: 25.6% vs 14.7%). Median CD4-cells: 286.5
      cells/uL (IQR: 168.8-482.8) versus 574 cells/uL (IQR: 406-786). 96.1% of the
      living HIV+ with CVE had HIV-RNA<50 copies/mL and median CD4-cells 542.5 cells/uL
      (IQR: 370-793.5). CONCLUSIONS: Advanced clinical and immunological stages of HIV
      infection, but not the duration of ART, were associated with higher incidences of
      CVE and deaths in the HIVH cohort. These observations support an earlier
      initiation of ART in HIV+. Special cardiovascular risk calculations for HIV+
      should consider immunological and clinical categories of the HIV-infection.

PMID- 25394051
TI  - Comparison of oxidative stress markers in HIV-infected patients on efavirenz or
      atazanavir/ritonavir-based therapy.
AB  - INTRODUCTION: Chronic low-grade inflammation and immune activation may persist in
      HIV patients despite effective antiretroviral therapy (ART). These abnormalities
      are associated with increased oxidative stress (OS). Bilirubin (BR) may have a
      beneficial role in counteracting OS. Atazanavir (ATV) inhibits UGT1A1, thus
      increasing unconjugated BR levels, a distinctive feature of this drug. We
      compared changes in OS markers in HIV patients on ATV/r versus efavirenz (EFV)
      based first-line therapies. MATERIALS AND METHODS: Cohort of the Spanish Research
      Network (CoRIS) is a multicentre, open, prospective cohort of HIV-infected
      patients naive to ART at entry and linked to a biobank. We identified hepatitis C
      virus/hepatitis B virus (HCV/HBV) negative patients who started first-line ART
      with either ATV/r or EFV, had a baseline biobank sample and a follow-up sample
      after at least nine months of ART while maintaining initial regimen and being
      virologically suppressed. Lipoprotein-associated Phospholipase A2 (Lp-PLA2),
      Myeloperoxidase (MPO) and Oxidized LDL (OxLDL) were measured in paired samples.
      Marker values at one year were interpolated from available data. Multiple
      imputations using chained equations were used to deal with missing values. Change
      in the OS markers was modelled using multiple linear regressions adjusting for
      baseline marker values and baseline confounders. Correlations between continuous
      variables were explored using Pearson's correlation tests. RESULTS: 145 patients
      (97 EFV; 48 ATV/r) were studied. Mean (SD) baseline values for OS markers in EFV
      and ATV/r groups were: Lp-PLA2 [142.2 (72.8) and 150.1 (92.8) ng/mL], MPO [74.3
      (48.2) and 93.9 (64.3) ug/L] and OxLDL [76.3 (52.3) and 82.2 (54.4) ug/L]. After
      adjustment for baseline variables patients on ATV/r had a significant decrease in
      Lp-PLA2 (estimated difference -16.3 [CI 95%: -31.4, -1.25; p=0.03]) and a
      significantly lower increase in OxLDL (estimated difference -21.8 [-38.0, -5.6;
      p<0.01] relative to those on EFV, whereas no differences in MPO were found.
      Adjusted changes in BR were significantly higher for the ATV/r group (estimated
      difference 1.33 [1.03, 1.52; p<0.01]). Changes in BR and changes in OS markers
      were significantly correlated. CONCLUSIONS: In virologically suppressed patients
      on stable ART, OS was lower in ATV/r-based regimens compared to EFV. We
      hypothesize these changes could be in part attributable to increased BR plasma
      levels.

PMID- 25394052
TI  - Epi-aortic lesions, pathologic FMD, endothelial activation and inflammatory
      markers in advanced naive HIV-infected patients starting ART therapy.
AB  - INTRODUCTION: PREVALEAT II (PREmature VAscular LEsions and Antiretroviral Therapy
      II) is an ongoing multicenter, longitudinal cohort study aimed to the evaluation
      of cardiovascular (CV) risk in advanced HIV-infected antiretroviral (ARV) naive
      patients starting their first antiretroviral therapy (ART). PATIENTS AND METHODS:
      All consecutive naive patients with CD4 cell count<200/mL starting any PI/r-based
      or NNRTI-based + 2 NRTIs regimen from January 2010 to January 2013 in the
      participant centres were enrolled. At baseline and after 3 (T1), 6 (T2) and 12
      (T3) months patients were subjected to epi-aortic vessels ultrasonography and
      brachial artery flow mediated dilation (FMD). Viral load, CD4+ cell count, serum
      lipid values, serum glucose, endothelial activation (ICAM-1 and VCAM-1) and
      inflammatory markers (IL-6 and hsCRP) values were recorded at the same time. Data
      about independent risk factors for HIV infection and CV disease are taken at time
      0. We enrolled 94 patients: 81% males, 87% caucasians, 40% smokers, 8.2% HCV co
      infected and 3.5% with lipodystrophy; 33% of them were homosexuals, 12% drug
      addicts; 23% were AIDS at presentation. Statistical data analysis has been
      conducted by the chi(2) nonparametric method. RESULTS: In Table 1 it is reported
      the percentage of patients with pathologic values, moreover, at T3, 60.46% showed
      undetectable viraemia and 69.77% had CD4 + > 200. CONCLUSIONS: Our data evidence
      at baseline has a relevant deterioration of CV conditions in terms of
      ultrasonographic data, FMD, inflammation and cytokine markers among advanced
      naives. During follow-up epi-aortic lesions tend to worsen but not significantly,
      percentage of pathologic FMD remains stable. Regarding markers of endothelial
      activation ICAM-1 significantly worsens during the period of observation; also
      VCAM-1 has a trend towards the worsening while not significantly. Conversely, a
      significant improvement was observed for the markers of inflammation D-dimers and
      high sensitivity C-reactive protein (hsCRP). IL-6 improved but not significantly.
      Serum lipid profile shows an increase of HDLc and total cholesterol, but not of
      LDLc. In conclusion, after a twelve-month follow-up period, CV risk of the
      patients remains high. ARV therapy seems in fact to improve only non-specific and
      poor sensitive inflammation biomarkers and HDLc; markers of endothelial
      activations tend to worsen, intima-media ultrasonography and FMD do not show
      relevant modifications. Further data are warranted to better understand the role
      of the different ARV regimens.

PMID- 25394053
TI  - Effectiveness of a team intervention in reducing modifiable cardiovascular
      disease risk in HIV-infected subjects on antiretroviral therapy.
AB  - INTRODUCTION: The increasing age, higher modifiable and inherent cardiovascular
      disease (CVD) risk of HIV-infected patients [1] necessitates improved approaches
      to reducing co-morbidities. We aimed to assess the effectiveness of a team
      intervention in reducing modifiable CVD risk. MATERIALS AND METHODS: HIV-infected
      patients >=50 years attending a large HIV caseload primary-care practice, who
      were virologically suppressed on antiretroviral therapy (ART), with moderate or
      severe 10-year CVD Framingham risk (>=10%) were recruited for this prospective
      case-control study. Intervention participants were provided a team approach to
      care, which involved treatment by study doctors for lipid, hypertension and ART
      management, and monthly review by a team of research nurses and dieticians for
      smoking cessation, exercise and dietary advice over 12 months. Controls were
      matched on age and smoking status, and were given standard of care (SOC) by non
      study doctors. Outcomes included CVD risk factors, body composition and CVD risk
      assessment, including Framingham 10-yr risk [2] and D:A:D 5-year estimated risk
      of coronary heart disease (CHD) [3]. Repeated measures analysis of variance was
      used to examine pre- and post-intervention differences, with p-values used to
      assess time and main effects of approach to care (Intervention, SOC). RESULTS: A
      total of 33 patients completed the intervention, with 33 controls (58.0+/-6.8 and
      59.1+/-6.9 years, respectively). Smoking cessation occurred in 25% cases versus
      nil controls. There was a significant change in CVD risk between intervention and
      control groups, in both Framingham scores (time and group*time interaction) and
      D:A:D scores (group*time interaction only) (Table 1). There was also a
      significant difference in change in total cholesterol over the study period (time
      and group*time interaction). Body composition was only measured in intervention
      patients, with a significant loss in % body fat observed in pre- and post
      intervention. CONCLUSIONS: Team intervention was significantly more effective
      than standard of care in reducing CVD risk in HIV-infected patients on ART. A
      team approach to care may be an important component of reducing CVD risk in this
      population.

PMID- 25394054
TI  - Evolution of Framingham cardiovascular risk score in HIV-infected patients
      initiating EFV- and LPV/r-based HAART in a Latin American cohort.
AB  - INTRODUCTION: Epidemiological studies suggest that some antiretroviral drugs may
      contribute to increase cardiovascular risk in HIV-infected patients. However,
      data from Latin American countries are limited, as impact of HAART on
      cardiovascular risk remains understudied. In this context, we aimed to evaluate
      if 10-year Framingham Cardiovascular Risk Score (FCRS) increases in patients
      following exposure to EFV- and LPV/r-based HAART in a Latin American cohort.
      MATERIALS AND METHODS: Retrospective 48-week cohort study. We reviewed clinical
      charts of randomly selected samples of patients initiating (according to national
      guidelines) EFV first-line HAART and LPV/r first- or second-line (but first PI
      based) HAART assisted at a reference HIV centre in Buenos Aires, Argentina
      (period 2004-2012). Each patient could only be included in one arm. FCRS was
      calculated according to National Institutes of Health risk assessment tool
      (http://cvdrisk.nhlbi.nih.gov/). RESULTS: A total of 357 patients were included:
      249 in EFV arm and 108 in LPV/r arm (80 as first line and 28 as second line, but
      first PI-based HAART). Baseline characteristics (median, interquartile range):
      age, 38 (33-45) years; male, 247 (69%); viral load, 98200 (20550-306000)
      copies/mL; CD4 T-cell count, 115 (60-175) cel/uL; total cholesterol, 159 (135
      194) mg/dL; HDL: 39 (31-41) mg/dL; LDL: 94 (72-123) mg/dL; current smoker, 29%;
      on antihypertensive drugs: 14 (4%), diabetic: 4 (1%). Most frequent accompanying
      nucleoside reverse transcriptase inhibitors (NRTIs) were 3TC (92%) and zidovudine
      (AZT; 76%). Baseline FCRS was low, moderate and high for 93%, 7% and 0% of
      patients on EFV arm and 96.7%, 1.7% and 1.7% on LPV/r arm. On EFV arm, an
      increase in FCRS category (low to moderate or moderate to high) was observed in 1
      patient (0.9%) at 24 weeks and 6 (5,6%) at 48 weeks; 5 (4.7%) decreased category.
      On LPV/r arm no one varied FCRS category at 24 weeks and 2 (3.4%) increased from
      low to moderate at 48 weeks (no patient decreased FCRS category). Cumulative
      incidence of overall cardiovascular events was 1.6% on EFV and 1.8% on LPV/r arms
      respectively. Probability of increasing FCRS category or having a cardiovascular
      event did not differ between arms at a significance level of 5%. CONCLUSIONS:
      Probability of increasing FCRS category and cardiovascular events was low and
      similar in patients exposed to EFV versus LPV/r-based HAART in a Latin American
      cohort. ClinicalTrials.gov Identifier: NCT01705873.

PMID- 25394055
TI  - Cardiovascular markers of inflammation and serum lipid levels in HIV-infected
      patients with undetectable viraemia.
AB  - INTRODUCTION: Successfully treated HIV-infected patients may still have an
      increased risk for cardiovascular morbidity and mortality, which might be related
      not only to traditional risks, but also to inflammation and dyslipidemia induced
      by HIV and/or antiretroviral therapy [1, 2]. We examined the relationship of
      serum lipid levels with plasma biomarkers of inflammation using a composite
      inflammatory burden score (IBS) from the following seven markers of inflammation:
      CD40L, tPA, MCP-1, IL-8, IL-6, hCRP and P-selectin. MATERIALS AND METHODS:
      Subjects were selected among consecutive HIV-infected males >=18 years of age
      with an undetectable viral load (<50 copies/mL of HIV1-RNA), seen at the
      University Hospital for Infectious Diseases, Zagreb, Croatia, in the period from
      January 2012 to March 2013. Plasma inflammatory biomarkers (CD40L, tPA, MCP-1, IL
      8, IL-6, hCRP and P-selectin, quantified by bead-based cytometry) >75th
      percentile were considered elevated and an IBS was constructed as the presence of
      zero, one, two, or three or more elevated biomarkers. Correlations between the
      IBS and lipid parameters were examined using Spearman's Rho and by ordered
      logistic regression proportional odds model to estimate the odds of more elevated
      (>75th percentile) biomarkers. RESULTS: 181 male patients were included into the
      study, the median age was 46.7 (Q1-Q3, 39.9-55.0) years and the median current
      CD4 cell count was 553.0 (Q1-Q3, 389-729) per microliter. The patients were
      mainly treated with two nucleoside reverse transcriptase inhibitor (NRTI) plus
      one non-NRTI (NNRTI) (N=100, 60.8%) or two NRTI plus lopinavir (N=50, 27.6%).
      There was a significant correlation between the IBS and serum cholesterol
      (Rho=0.23, 95% CI, 0.09-0.37), triglycerides (Rho=0.30, 95% CI, 0.16-0.42) and
      cholesterol/HDL-cholesterol ratio (Rho=0.25, 95% CI 0.11-0.38). In the
      multivariable model a one unit increase in cholesterol/HDL-cholesterol ratio was
      associated with a 1.72-fold (95% CI, 1.27-2.33) increased odds of having a
      greater IBS. One unit increase (mmol/L) of cholesterol and triglycerides was
      associated with a 1.41-fold (95% CI, 1.13-1.76) and 1.37-fold (95% CI, 1.18-1.60)
      increased odds of having a greater IBS, respectively. CONCLUSIONS: Our study
      suggests that in virologically suppressed patients there is a significant
      association between markers of inflammation and serum levels of cholesterol and
      triglycerides as well as the cholesterol/HDL-cholesterol ratio.

PMID- 25394056
TI  - Prevalence and concordance of high cardiovascular disease scores in HIV/AIDS
      patients from Croatia and Serbia with four international algorithms.
AB  - INTRODUCTION: We evaluated cardiovascular risks in HIV-infected patients from
      Croatia and Serbia and the eligibility for statin therapy as recommended by the
      2013 American College of Cardiology/American Heart Association (ACC/AHA)
      guidelines, European AIDS Clinical Society (EACS) Guidelines and European Society
      of Cardiology and the European Atherosclerosis Society (ESC/EAS) guidelines for
      cardiovascular disease (CVD) prevention [1-3]. MATERIALS AND METHODS: A cross
      sectional analysis of consecutive patients between 40 and 79 years old who had
      received antiretroviral therapy for at least 12 months was performed. RESULTS: Of
      254 (132 from Croatia and 122 from Serbia) persons included in the study, 76%
      were male; median age was 49 years. Up to 51.6% of persons had a high CVD risk.
      The prevalence of current smoking was 42.9%, hypertension 31.5% and
      hypercholesterolaemia (>6.2 mmol/L) 35.4%. Statins would be recommended to 21.3%
      (95% CI, 16.3% to 27.4%) of persons by the EACS, 25.6% (95% CI, 20.2% to 31.9%)
      by ESC/EAS and 37.9% (95% CI, 31.6 to 44.6%) by the ACC/AHA guidelines. A high 5
      year data collection on adverse effects of anti-HIV drugs study risk score (>5%)
      had a moderate agreement with the high (>=20%) 10-year CVD Framingham risk score
      (kappa=0.47) and high (>=5%) 10-year European systematic coronary risk evaluation
      score algorithm (kappa=0.47), and substantial agreement with the elevated
      (>=7.5%) 10-year Pooled Cohort Atherosclerotic CVD risk equation score
      (kappa=0.63). CONCLUSION: We found a high prevalence of CVD risks in patients
      from Croatia and Serbia. The ACC/AHA guideline would recommend statins more often
      than ESC/EAS and EACS guidelines.

PMID- 25394057
TI  - Randomized, crossover, double-blind, placebo-controlled trial to assess the lipid
      lowering effect of co-formulated TDF/FTC.
AB  - INTRODUCTION: Previous studies have described improvements on lipid parameters
      when switching from other antiretroviral drugs to tenofovir (TDF) and impairments
      in lipid profile when discontinuing TDF. [1-3] It is unknown, however, if TDF has
      an intrinsic lipid-lowering effect or such findings are due to the addition or
      removal of other offending agents or other reasons. MATERIALS AND METHODS: This
      was a randomized, crossover, double-blind, placebo-controlled clinical trial (NCT
      01458977). Subjects with HIV-1 RNA <50 copies/mL during at least 6 months on
      stable DRV/r (800/100 mg QD) or LPV/r (400/100 mg BID) monotherapy, with
      confirmed fasting total cholesterol >=200 or LDL-cholesterol >=130 mg/dL and not
      taking lipid-lowering drugs were randomized to (A) adding TDF/FTCduring 12 weeks
      followed by 24 weeks without TDF/FTC, or (B) continuing without TDF/FTC for 12
      weeks, adding TDF/FTC for 12 weeks and then withdrawing TDF/FTC for 12 additional
      weeks. Randomization was stratified by DRV/r or LPV/r use at study entry. All
      subjects received a specific dietary counselling. Primary endpoints were changes
      in median fasting total, LDL and HDL-cholesterol 12 weeks after TDF/FTC addition.
      Analyses were performed by ITT. RESULTS: 46 subjects with a median age of 43 (40
      48) years were enrolled in the study: 70% were male, 56% received DRV/r and 44%
      LPV/r. One subject withdrew the study voluntarily at week 4 and another one
      interrupted due to diarrhoea at week 24. Treatment with TDF/FTC decreased total,
      LDL and HDL-cholesterol from 235.9 to 204.9 (p<0.001), 154.7 to 127.6 (p<0.001)
      and 50.3 to 44.5 mg/dL (p<0.001), respectively. In comparison, total, LDL and HDL
      cholesterol levels remained stable during placebo exposure. Week 12 total
      cholesterol (p<0.001), LDL-cholesterol (p<0.001) and HDL-cholesterol (p=0.011)
      levels were significantly lower in TDF/FTC versus placebo. Treatment with TDF/FTC
      reduced the fraction of subjects with abnormal fasting total-cholesterol (>=200
      mg/dL) from 86.7% to 56.8% (p=0.001) and LDL-cholesterol (>=130 mg/dL) from 87.8%
      to 43.9% (p<0.001), which was not observed with placebo. There were no
      virological failures, and CD4 and triglyceride levels remained stable regardless
      of exposure. CONCLUSION: Coformulated TDF/FTC has an intrinsic lipid-lowering
      effect, likely attributable to TDF.

PMID- 25394058
TI  - Early changes in coagulation but not inflammatory biomarkers under intermittent
      ART: the randomized ANRS 106 WINDOW trial.
AB  - INTRODUCTION: In the SMART trial, baseline plasma hsCRP, IL6 and D-dimer levels
      were strongly correlated to all-cause mortality. A case-control study has shown
      an increase of IL-6 and D-dimer levels after one month of antiretroviral therapy
      (ART) interruption, which was correlated to viral load. Restarting ART was
      associated to a decrease in D-dimer but not IL-6 or hsCRP levels. We assessed
      biomarkers levels up to 96 weeks in ART-experienced adults with plasma HIV RNA
      levels <400 c/mL randomized in the ANRS 106 WINDOW trial to intermittent ART (IT:
      six cycles of eight weeks of ART interruption followed by eight weeks of ART)
      versus continuous treatment (CT). METHODS: Stored plasma for 160 participants (80
      IT and 80 CT), matched by age, sex and CDC classification, were analyzed blinded
      for IL-6, sCD-14, hsCRP and D-dimer levels at baseline, week 8 (IT group only),
      week 16 and week 96. Lower levels of detection for IL-6, sCD14, hsCRP and D-Dimer
      were 1.5 pg/mL, 250 ng/mL, 0.03 ug/mL and 0.21 ug/mL, respectively. The primary
      objective was to compare changes in IL-6, hsCRP, sCD14 and D-dimer plasma levels
      from baseline to week 8, 16 and 96 in the IT and CT arms. Biomarkers levels were
      log10 transformed prior to analysis. RESULTS: At baseline, patients were mostly
      men (86%), with a median age of 40 years, a CD4+ T-cell count of 768/mm(3), have
      received a median of 4.7 years of ART and 85% had HIV RNA <50 c/mL. Proportion of
      patients with plasma HIV RNA levels<400 c/mL were 6% and 99%, 81% and 97%, 86%
      and 92% at weeks 8, 16 and 96 in the IT and CT arms, respectively. Plasma
      biomarkers levels are shown in the Table 1. CONCLUSION: Coagulation and
      inflammatory biomarkers levels remained stable over 96 weeks in well-suppressed
      HIV-infected patient on ART. Following ART interruption there was a significant
      increase in D-dimer but not in inflammatory biomarkers levels. This increase was
      reversed upon reintroduction of ART. These data suggest that ART interruption
      increases coagulation rather than inflammatory biomarkers.

PMID- 25394059
TI  - Higher rates of metabolic syndrome among women taking zidovudine as compared to
      tenofovir in rural Africa: preliminary data from the CART-1 study.
AB  - INTRODUCTION: Due to its side effects stavudine (D4T) has been replaced by
      zidovudine (AZT) and tenofovir (TDF) in most low- and middle-income countries
      (LMICs). In 2014 about 38% of adult first-line regimens contain AZT and 62% TDF
      [1]. Whereas the unfavourable metabolic outcomes of D4T in comparison to TDF have
      been described extensively, studies from LMICs comparing metabolic profiles
      between patients on AZT and TDF are scarce. Given the high number of patients in
      LMICs still taking AZT, data on their metabolic profile are needed. We present
      rates of metabolic syndrome (MS) in adult patients taking either AZT- or TDF
      containing first-line, non-nucleoside reverse transcriptase (NNRTI)-based
      regimens. MATERIALS AND METHODS: Data derived from a cross-sectional multi
      disease screening conducted in ten facilities in two rural districts of Lesotho,
      Southern Africa [2]. Patients were eligible if aged >=25 years and on NNRTI
      containing first-line ART >=6 months. The MS definition for Africa of the
      International Diabetes Federation was applied [3]. Assessed potential predictors
      for MS were age, time on ART, virologic suppression, body-mass index (BMI),
      alcohol consumption, wealth quintile, NNRTI (nevirapine (NVP) or Efavirenz
      (EFV)), history of previous D4T exposure and ART-backbone (AZT or TDF).
      Statistical analyses - stratified for sex - comprised univariate logistic
      regression for each predictor variable with subsequent construction of a
      multivariate model including all predictors with an association to MS at a
      significance level<0.1 in univariate analysis. RESULTS: Out of 1026 patients, 660
      (64.3%) were female. MS prevalence was 9.8% (95% CI 6.9-13.4) in men and 22.9%
      (19.7-26.3) in women. In women, aged >=35 years, AZT-backbone, NVP-base, BMI
      >=25kg/m2 and taking ART for >=4.5 years were associated with MS in univariate
      analysis. In the multivariate model only AZT (adjusted odds-ratio: 2.2, 95% CI
      1.4-3.6; p=0.001) and BMI >=25kg/m2 (9.8; 2.8-34.1, p<0.001) were associated with
      MS. For men, age, higher wealth quintile, history of D4T exposure and BMI were
      associated with MS in univariate analysis. In the multivariate model only a BMI
      >=25kg/m2 was associated with MS (8.9; 3.8-20.9, p<0.001). CONCLUSIONS: In rural
      Lesotho, Southern Africa, the use of AZT instead of TDF among women who are on
      ART for >=6 months predisposes to the development of metabolic syndrome. Given
      that, still 38% of first-line regimens in LMIC contain AZT, this finding needs to
      be verified in other settings in Sub-Saharan Africa.

PMID- 25394060
TI  - Long-term fat redistribution in ARV-naive HIV+ patients initiating a non
      thymidine containing regimen in clinical practice.
AB  - INTRODUCTION: Lipodystrophy is still a matter of concern in HIV+ patients
      receiving ART. However, long-term fat change in patients taking non-thymidine
      regimens is not well known. MATERIALS AND METHODS: A prospective ongoing fat
      change assessment including clinical evaluation and dexa scans (Hologic QDR 4500)
      is being conducted in all consecutive patients initiating ART from January 2008.
      Arm, leg, trunk and total fat as well as fat mass ratio (FMR=% trunk fat/% leg
      fat) were determined. Patients with data at baseline (BL), 12 and 36 m are
      included in this analysis. ITT and OT were performed. Multivariate general linear
      models were used to assess changes in fat measures. RESULTS: One hundred patients
      were included. 81% men, 42.9 years, 18% AIDS, CD4 218.5 (6-756), viral load 5 log
      (2.9-6.8), leg fat 4644g, trunk fat 6693g, FMR 0.94. Around 40 patients (40%)
      initiated a PIr (17 LPVr, 11 ATVr, 9 DRVr, 3 FPVr), 34 (34%) NVP and 21 (21%)
      EFV. About 83% received TDF/FTC and 10% ABC/3TC. Groups were comparable at BL
      except for a lower viral load in NVP patients (p=0.047) and lower c-LDL in PI
      patients (p=0.043). After 36 m, no patient presented a clinically evident
      lipodystrophy. At 12 m, an overall significant increase was found from baseline
      in trunk, leg and FMR (median 759 g, 479.4 g and 0.03, respectively, p<0.05) and
      at 36 m in trunk and leg fat (median 989.9 g, 566 g, respectively, p<0.05).
      According to ART, at 12 m a significant increase in trunk and leg fat was
      observed in EFV and PIr. At 36 m, in NVP patients trunk and leg fat as well as
      FMR increased, whereas in PIr patients only leg fat increased (see figure). In
      ITT analysis, adjusted by age, sex, risk practice and BL CD4, EFV was associated
      with a greater increase in FMR (p=0.036) at 36 m vs PIr. In OT analysis, at 12 m,
      NVP was associated with a smaller percentage increase in trunk fat (vs PIr and
      EFV, p=0.006) and in leg fat (vs PIr, p=0.046). These differences did not persist
      at 36 m. CONCLUSIONS: In this cohort of patients taking non-thymidine-based
      regimens, after 36 m without a clinically evident lipodystrophy, no significant
      changes in FMR were observed. However, some differences in fat redistribution
      according to ART were present: PIr was associated with an initial and continuous
      increase in trunk and leg fat, NVP with a slower and progressive increase in both
      fat compartments, while in EFV patients, the initial fat increase was followed by
      a decrease in peripheral fat at 36 m. Longer follow up will help to confirm these
      trends.

PMID- 25394062
TI  - Association between lipid genetic and immunological status in chronically HIV
      infected patients.
AB  - INTRODUCTION: Polymorphisms in some host genes have a significant impact on
      susceptibility to HIV-1 infection and rate of disease progression (1, 2). The
      purpose of the current sub-study was to find out the relationship between
      polymorphisms in genes involved in the lipid metabolism and the CD4/CD8 T-cell
      counts. METHODS: Sub-study of a cross-sectional, observational study conducted in
      468 patients with HIV infection attended at the outpatient clinic to investigate
      individual genetic predisposition to atherogenic dyslipidemia (AD). All patients
      were genetically characterized and all polymorphisms were in Hardy-Weinberg
      equilibrium. Thirteen polymorphisms were selected from nine genes: APOA5
      (rs662799 and rs3135506); APOC3 (rs5128 and rs4520); LPL (rs328 and rs268); CETP
      (rs708272); HL (rs1800588); MTP (rs1800591); APOE (rs7412 and rs429358); LRP5
      (rs7116604); and VLDLR (rs1454626). Lipid and lipoprotein parameters, CD4 and CD8
      T-cell counts and plasma HIV-RNA were determinate. The statistical analysis was
      performed using SPSS statistical software version 19 (SPSS Inc., Chicago, IL,
      USA). RESULTS: We studied 468 HIV-infected patients (men, 77%), with a mean (SD)
      age of 45.9 (19.7) years. The mean CD4 T-cell count and nadir CD4 was 547 (459)
      and 193 (159) cells/uL, respectively; 78.7% of participants were virologically
      suppressed. Patients carrying rs3135506 in the APOA5 gene presented a 9% increase
      in circulating TG levels (p=0.002) and 10% decrease in HDLc levels (p=0.005).
      Such association of APOA5 towards dyslipidemia was accompanied by a 21% decrease
      of the CD4 T-cell count (p=0.024) and a 19% increase in CD8 T-cell count
      (p=0.002) in carriers of the rare allele in the APOA5 rs662799 polymorphism
      adjusted by age and gender. Patients carrying the rare allele in rs5128 (APOC3)
      had a 16% decrease in circulating CD4 T cells (p=0.029); patients carrying
      rs1800591 (MTP) had a 29% decrease in CD4 T cells and 14% decrease in CD8 T cells
      (p=0.018 and p=0.008, respectively); patients carrying the rare allele rs1800588
      in HL had a 11% increase in CD4 T cells (p=0.043); and carriers of the rs145626
      in the VLDLR gene had 10% decrease in CD4 circulating T cells (p=0.013).
      CONCLUSION: Variants in genes involved in the development of AD may also
      influence the immunological host-virus equilibrium in chronically HIV-infected
      subjects (2, 3).

PMID- 25394061
TI  - Changes in lipid levels after 48 weeks of dual versus triple therapy observed in
      the GARDEL study.
AB  - INTRODUCTION: Treatment with ritonavir-boosted protease inhibitors and nucleoside
      analogues frequently leads to rises in lipids, which might increase the
      cardiovascular risk. The aim of this study was to describe changes in lipid
      levels among HIV positive patients participating in the GARDEL study. MATERIALS
      AND METHODS: The GARDEL study compared the efficacy and safety of a dual therapy
      (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT)
      with LPV/r 400/100 mg BID+3TC or FTC and a third investigator-selected NRTI in
      fixed-dose combination among HIV+ treatment naive patients. We compared changes
      in lipid levels from baseline to week 48 in both arms. RESULTS: Patient's
      characteristics were well balanced regarding mean baseline total cholesterol (157
      mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL-C (94
      mg/dL DT, 91 mg/dL TT) and HDL-C (36 mg/dL DT, 35 mg/dL TT). Changes in total
      cholesterol, LDL-C and HDL-C were higher in DT arm, compared to TT (32% DT vs 26%
      TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL).
      Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT)
      (Table 1). In TT arm LDL-C and total cholesterol elevations were lower among
      patients receiving TDF compared to those treated with ZDV or ABC. CONCLUSION:
      Changes in lipid parameters were observed in both arms. Albeit the increase was
      numerically higher for cholesterol (total and LDL-C) in DT arm while TT arm had
      higher increases in TG; no difference was observed when week 48 values were
      compared with the NCEP ATP III goals for cardiovascular risk reduction (1). So,
      the DT strategy, even missing the lipid-lowering effect observed with tenofovir,
      does not seem to add significant risk to patients treated with this novel
      strategy.

PMID- 25394063
TI  - Lipid-lowering agents for dyslipidemia in patients who were infected with HIV in
      Taoyuan, Taiwan.
AB  - INTRODUCTION: There is no doubt that highly active antiretroviral therapy (ART)
      has decreased the total mortality of HIV-infected populations drastically, and
      HIV has become a chronic and manageable condition. However, complications after
      long-term treatment of ART tarnished the great efforts. We aimed to study the
      effects of add-on lipid-lowering agents on ART for patients who developed
      hyperlipidemia after HIV treatment. The risk factors for failure to normalize
      lipid profile were analyzed. MATERIALS AND METHODS: HIV-infected patients who
      visited outpatient clinics of Taoyuan General Hospital between July 2013 and
      January 2014 were retrospectively reviewed. Subjects who needed the management of
      dyslipidemia were enrolled. Total cholesterol (TC), triglyceride (TG), high
      density lipoprotein (HDL) and low-density lipoprotein (LDL) were regularly
      followed up for at least 6 months. ART modification and add-on lipid-lowering
      agents for dyslipidemia were analyzed. RESULTS: There were 926 HIV-infected
      patients undertaking ART in the hospital during the study period. Among them,
      23.2% of patients undergoing lopinavir-based regimen, 8.4% efavirenz-based
      regimen, 4.2% darunavir-based regimen, 3.3% nevirapine-based regimen, 2.4%
      raltegravir-based regimen and 2.3% atazanavir-based regimen developed
      dyslipidemia. There were 76 patients (8.2%) who needed management of dyslipidemia
      (Table 1). Among them, 97% received lipid-lowering agents, and 17% switched to
      lipid-friendly ART (atazanavir, boosted atazanavir, boosted darunavir, nevirapine
      or raltegravir) despite statins or fibrates used. Mean values (mg/dL) of TC/
      TG/LDL were, respectively, 279/422/139 before enrolment, 209/270/114 at 4-12
      weeks and 206/250/121 at 48 weeks (p<0.05 for baseline compared to 4-12 weeks and
      1 year, respectively). No obvious changes in HDL were noted. In Cox proportional
      hazard model, patients who received lopinavir (adjusted hazard ratio [aHR],
      0.293; 95% confidence interval [CI], 0.110-0.784; p=0.015) or efavirenz (aHR,
      0.185; 95% CI, 0.072-0.447; p=0.005) were less likely to achieve normalization of
      TC (<200 mg/dL) and TG (<200 mg/dL). Modification of ART (aHR, 1.807; 95% CI,
      0.828-3.944; p=0.137) did not change the outcome (Figure 1). CONCLUSIONS:
      Efavirenz and lopinavir were independent factors for the persistence of
      dyslipidemia despite adding lipid-lowering agents. ART associated with a
      favourable lipid profile would be considered in the modern era, and this
      certainly leaves the question of cost versus benefit.

PMID- 25394064
TI  - Polymorphisms in LPL, CETP, and HL protect HIV-infected patients from atherogenic
      dyslipidemia in an allele-dose-dependent manner.
AB  - INTRODUCTION: HIV-infected patients treated with Highly Active Antiretroviral
      Therapy (HAART) may be predisposed to hypertriglyceridemia, which gives rise to a
      highly atherogenic lipid profile known as atherogenic dyslipidemia (AD). We
      propose that genetic variability leaves some HIV-infected patients more
      predisposed to AD than others (1, 2). METHODS: This was a cross-sectional,
      observational study conducted in 468 antiretroviral-treated HIV-infected patients
      attending at the outpatient clinic of a tertiary hospital over a 6-month period,
      who were classified as normolipidemic (n=173) or presenting with AD
      (triglycerides: 1.7 mmol/L and HDLc < 1.02 [men] or 1.28 mmol/L [women]) (n=148).
      Polymorphisms were identified in the APOA5, APOC3, LPL, CETP, HL, MTP, APOE, LRP5
      and VLDLR genes. RESULTS: Atherogenic dyslipidemia was detected in 31% of
      patients, most of whom were men (77%). This group was also older and had higher
      levels of remnant lipoprotein cholesterol (RLPc) than normolipidemic patients.
      The polymorphisms rs328 in LPL, rs708272 in CETP and rs1800588 in HL were 10-40%
      significantly more frequent in normolipidemic patients. At least 1 of these
      polymorphisms was detected in 90% of normolipidemic patients; in AD patients, the
      percentage decreased to 75% (p=0.003). This effect was dependent on both the
      allele and the dose of HAART and independent of the regimen administered. The
      protective combination showed a trend towards higher HDLc (1.13 [0.40] vs 1.24
      [0.23] mmol/L), lower triglycerides (2.23 [2.34] vs 1.89 [1.24] mmol/L) and lower
      RLPc (16.41 [11.42] vs 12.99 [11.69] mmol/L). CONCLUSIONS: Polymorphisms in LPL,
      CETP and HL protect HIV-infected patients from developing AD in a dose-dependent
      manner (3).

PMID- 25394065
TI  - Estimation of the true incidence of lactic acidosis within the Lighthouse Clinic
      cohort, and the likely magnitude of missed diagnoses in the region.
AB  - INTRODUCTION: Lactic acidosis is one of the most serious side effects associated
      with ART, most commonly associated with stavudine. Clinical features are non
      specific and specialist laboratory capabilities are essential to confirm the
      diagnosis, making under-diagnosis likely in resource-constrained settings.
      Lighthouse Trust is a tertiary referral ART centre with over 23,500 patients on
      ART. The adjacent University of North Carolina Project laboratory, also serving
      Kamuzu Central Hospital, has been the only site processing lactate tests in
      Central Zone for many years. Our objective was to quantify the true incidence
      within our cohort, and estimate the likely degree of historical missed diagnoses
      from less central ART clinics. METHODS: All high lactate results between June
      2010 and June 2013 were treated as cases, and cross referenced with the
      Lighthouse database. Patients transferring in to Lighthouse within one month
      prior to diagnosis were assumed to have been referred due to their lactic
      acidosis, and moved to the Central Zone cohort to avoid referral bias. Routinely
      collected quarterly ART cohort data for both Lighthouse and the entire Central
      Zone were analyzed. RESULTS: Over the three-year period, from within the
      Lighthouse cohort, there were 138 cases: 74% were female, median duration on ART
      was 14 months (IQR 10-26), and 98.5% were attributable to stavudine (only two
      cases to zidovudine). Over this period, the average number of patients taking
      stavudine at Lighthouse was 10,960 (3,600 on zidovudine). For the whole Central
      Zone (minus Lighthouse patients) there were 61,000 on stavudine (4,830 on
      zidovudine), yet only 124 cases of lactic acidosis were apparently diagnosed from
      within this cohort. CONCLUSIONS: Although cases may, of course, also have been
      missed at Lighthouse, as a tertiary referral centre the rate observed is likely
      to be closer to the true incidence. Over the three years, with 138 cases from the
      10,960 patients taking stavudine at Lighthouse, it is likely that somewhere in
      the region of 700 additional cases occurred amongst the 61,000 patients elsewhere
      in the Central Zone. This equates to somewhere in the region of 550 missed
      diagnoses or 80% of all cases. Given that the clinical sequelae of undiagnosed
      lactic acidosis are either death or at best ART default, this provides further
      vindication for the decision to phase out stavudine in Malawi.

PMID- 25394066
TI  - Lipohypertrophy and metabolic disorders in HIV patients on antiretroviral
      therapy: a systematic multidisciplinary clinical approach.
AB  - INTRODUCTION: Morphological and metabolic complications in HIV patients on
      antiretroviral therapy remain a challenge. While new cases of lipoatrophy (LA)
      disappear, irreducible central lipohypertrophy (LH) and metabolic complications
      require highly specialized management. We described a day hospital dedicated to
      lipodystrophy (LD) and metabolic disorders in HIV patients on treatment in
      Geneva, Switzerland, with a focus on LH. MATERIALS AND METHODS: The "Groupe Lipo
      & Metabolism" is a multidisciplinary consultation where patients undergo a
      standard evaluation including questionnaire, physical examination, dual-energy x
      ray absorptiometry (DEXA) and L5-level CT scans, blood tests and consultations
      with various specialists. Based on prospectively maintained data, we describe
      clinical, biological and radiological characteristics of patients >=18 years who
      attended the consultation between 2008 and 2013. We defined LH by CT scan, the
      gold standard method, as abdominal visceral adipose tissue (VAT) >=130 cm(2),
      value associated with increased risk of cardiovascular event. RESULTS: A total of
      195 patients attended the consultation during study period. Reasons for referral
      included LH in 28.3%, LA in 25% and mixed syndrome in 15.5% of cases. Metabolic
      disorders accounted for 19% of referrals with or without LD features. Among
      patients with a CT scan performed (n=183), 46 (25%) had LH with a VAT >=130
      cm(2). In this population, mean age was 49.1 years and 53.6% were male. HIV viral
      load was <50 cp/ml in 87% of patients. Mean body mass index was 24.6 kg/m(2).
      Mean waist to hip ratio (WHR) was 0.98 for males and 0.89 for females. A total of
      9.8%, 29.5% and 35% of patients had abnormal levels of total cholesterol (>=6.5
      mmol/L), triglycerides (>=2.0 mmol/L) and HDL cholesterol (<=1.0 mmol/L),
      respectively. Mean fasting glycaemia was 5.7 mmol/L and HbA1c was >6% in 10.5% of
      patients. Vitamin-D level was <75 nmol/L in 70.7% of patients. Respectively 31.2%
      and 12.1% of patients had osteopenia and osteoporosis on the spine and 44.8% and
      6.6% on the hip neck. Factors associated with a VAT>=130 cm(2) included male
      gender (OR 3.7 [95% CI 1.7-8.2] p<0.001), triglycerides >=2 mmol/L (OR 2.6 [95%
      CI 1.3-5.4] P<0.01) and increase in BMI category (OR 1.8 [95% CI 1.2-2.8]
      p<0.01). CONCLUSIONS: Lipohypertrophy is a prevalent feature of fat
      redistribution among HIV patients on treatment. Risk factors for LH include male
      gender, dyslipidemia and overweight. Glucose impairment and bone disorders are
      also common. A multidisciplinary approach is important to identify and promptly
      address these disorders. Acknowledgments: The "Groupe Lipo & Metabolism" team.

PMID- 25394067
TI  - Nephrolithiasis and renal failure among patients exposed to atazanavir, other PIs
      and PI-free regimens.
AB  - INTRODUCTION: Recent single-site studies and case reports have linked atazanavir
      (ATV) with the occurrence of nephrolithiasis. The purpose of this study was to
      estimate and compare the incidence rate of nephrolithiasis and to characterize
      the occurrence of subsequent renal failure among patients on ATV, other protease
      inhibitors (PIs) and PI-free regimens using real world data. MATERIALS AND
      METHODS: This was a retrospective cohort analysis using claims data from a US
      commercial and a US public health insurance database (Medicaid) spanning 2003
      2011 and 2006-2011, respectively. We identified adult HIV patients who were
      prescribed ATV, other PIs or PI-free regimens with at least 6 months of
      continuous enrolment prior to the index claim. Nephrolithiasis was defined as an
      inpatient or outpatient ICD-9 diagnosis code for nephrolithiasis or an associated
      condition, plus an imaging/corrective procedure code. Renal failure was also
      identified using diagnosis codes among patients experiencing nephrolithiasis.
      Hazard ratios were estimated using propensity score (PS) adjusted Cox regression,
      crude and adjusted for demographics, baseline comorbidities and comedications.
      RESULTS: A total of 14,477 patients (ATV: 4,150; other PIs: 4,153; PI-free:
      6,174) were identified in the commercial database: 83% male and 20% age >=50
      years. In the Medicaid database, 9,104 patients (ATV: 3,460; other PIs: 3,117; PI
      free: 2,527) were identified: 53% male and 25% age >=50 years. There were
      significant baseline differences in demographics, comorbidities and concomitant
      medications among the three cohorts. In adjusted analyses, ATV use was not
      significantly associated with nephrolithiasis when compared to other PIs. When
      ATV was compared to PI-free regimens, a positive association was observed in the
      commercial insurance but not the Medicaid database. In both databases, previous
      history of nephrolithiasis was the strongest predictor of nephrolithiasis in the
      ATV/PI-free regimens contrast, but not the ATV/other PIs contrast. For the renal
      failure outcomes, there were insufficient cases across all cohorts to conduct
      crude or adjusted analyses (see Table 1). CONCLUSIONS: In this analysis of two
      large real world databases, we did not find evidence of an increased risk of
      nephrolithiasis among patients on ATV compared to other PIs. However, when ATV
      was compared to PI-free regimens, the results differed across the two databases,
      requiring further study. Additionally, renal failure following nephrolithiasis
      was infrequent and not significantly different across the three cohorts.

PMID- 25394068
TI  - The prevalence and predictive value of dipstick urine protein in HIV-positive
      persons in Europe.
AB  - INTRODUCTION: Proteinuria (PTU) is an important marker for the development and
      progression of renal disease, cardiovascular disease and death, but there is
      limited information about the prevalence and factors associated with confirmed
      PTU in predominantly white European HIV+ persons, especially in those with an
      estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m(2). PATIENTS AND
      METHODS: Baseline was defined as the first of two consecutive dipstick urine
      protein (DPU) measurements during prospective follow-up >1/6/2011 (when
      systematic data collection began). PTU was defined as two consecutive DUP >1+
      (>30 mg/dL) >3 months apart; persons with eGFR <60 at either DPU measurement were
      excluded. Logistic regression investigated factors associated with PTU. RESULTS:
      A total of 1,640 persons were included, participants were mainly white (n=1,517,
      92.5%), male (n=1296, 79.0%) and men having sex with men (n=809; 49.3%). Median
      age at baseline was 45 (IQR 37-52 years), and CD4 was 570 (IQR 406-760/mm(3)).
      The median baseline date was 2/12 (IQR 11/11-6/12), and median eGFR was 99 (IQR
      88-109 mL/min/1.73 m(2)). Sixty-nine persons had PTU (4.2%, 95% CI 3.2-4.7%).
      Persons with diabetes had increased odds of PTU, as were those with a prior non
      AIDS (1) or AIDS event and those with prior exposure to indinavir. Among females,
      those with a normal eGFR (>90) and those with prior abacavir use had lower odds
      of PTU (Figure 1). CONCLUSIONS: One in 25 persons with eGFR>60 had confirmed
      proteinuria at baseline. Factors associated with PTU were similar to those
      associated with CKD. The lack of association with antiretrovirals, particularly
      tenofovir, may be due to the cross-sectional design of this study, and additional
      follow-up is required to address progression to PTU in those without PTU at
      baseline. It may also suggest other markers are needed to capture the
      deteriorating renal function associated with antiretrovirals may be needed at
      higher eGFRs. Our findings suggest PTU is an early marker for impaired renal
      function.

PMID- 25394069
TI  - Impact of NRTI backbone on renal, bone and cardiovascular markers in HIV-infected
      individuals receiving a boosted protease inhibitor.
AB  - INTRODUCTION: We have previously shown in the SSAT 044 study that unconjugated
      hyperbilirubinaemia in subjects receiving a boosted protease inhibitor (PI/r) has
      limited impact on renal, cardiovascular (CV) and bone biomarkers, as well as on
      neurocognitive performance, relative to those receiving PI/r with a normal
      bilirubin. We present here a secondary analysis comparing markers in those
      receiving abacavir- vs tenofovir- based antiretroviral therapy (ART). MATERIALS
      AND METHODS: This cross-sectional study included 101 HIV-1 infected individuals
      stable (HIV RNA<50 cps/ml, >6 months) on antiretroviral regimens including
      tenofovir (TDF)/emtricitabine or abacavir/lamivudine plus a ritonavir boosted PI.
      RESULTS: Forty-three subjects had normal bilirubin (NBR) levels and 35 had high
      bilirubin (>2.5 times upper limit); the remaining 23 patients had intermediate
      bilirubin levels or violated the protocol. The mean age of participants was 48
      years; 93% were male and 84% Caucasian; 22 received ABC-based therapy and 78 TDF.
      No differences were seen in cardiovascular markers: Framingham (10-year risk %
      median, IQR): ABC 8.1, 5.6-15.3; TDF 9.5, 4.8-13.4 (p=ns); pulse wave velocity
      and carotid intimal thickness also showed no significant differences. No
      differences were seen in bone parameters: Calcaneal Stiffness Index (median
      score, IQR): ABC -0.5, -0.8 to 0.8; TDF -0.5, 1.4-0.4 (p=ns); 10 year FRAX score
      (% median, IQR): ABC 5.0, 2.4-6.2; TDF 3.6, 2.5-5.8 (p=ns). There were
      differences in renal parameters as shown in Table 1. We show statistically
      significant differences in urine protein/creatinine ratio (uPCR) (10 vs 7;
      p=0.004) and urine albumin/creatinine ratio (uACR) (15 vs 8; p=0.002), with both
      being higher in the TDF group. CONCLUSIONS: Tenofovir use is associated with
      excess loss of proteins including those typically resorbed in the renal tubule.
      Abacavir use was not associated with an increase in biomarkers of CV risk or
      vascular dysfunction.

PMID- 25394070
TI  - Attitudes of serodiscordant couples towards antiretroviral-based HIV prevention
      strategies in Kenya: a qualitative study.
AB  - INTRODUCTION: Transmission in serodiscordant couples (SDCs) accounts for
      approximately half of all new HIV infections, both in Kenya and the wider sub
      Saharan region (1). With evidence to suggest inconsistent condom use within this
      population (2), the World Health Organization has recommended two new methods of
      HIV prevention for SDCs: Treatment as Prevention (TasP) and Pre-Exposure
      Prophylaxis (PrEP). However, there has been little research about the attitudes
      of SDCs towards these strategies (3, 4); knowledge that is paramount for
      successfully predicting the acceptability and efficacy of each method, as well as
      for informing decisions regarding HIV policy changes in Kenya. METHODS: An
      exploratory, qualitative study was conducted in the Muhoroni constituency of
      Nyando district, Kenya from January to March 2013. Purposive sampling was
      predominately used to recruit 21 HIV-positive and 17 HIV-negative individuals in
      a serodiscordant relationship from four hospitals and health centres. During face
      to-face semi-structured interviews, topic guides were used to elicit information
      about participants' attitudes and preferences towards TasP and PrEP. Collected
      data underwent framework analysis, allowing the development of overarching
      categories, sub-themes and inductive interpretation. RESULTS: The majority of
      participants, irrespective of gender and HIV status, found TasP more acceptable
      than PrEP. A key factor influencing this decision was HIV-negative participants'
      limited motivation to take and adhere to antiretrovirals (ARVs), primarily due to
      a predominantly external health locus of control, a lack of cultural acceptance
      of prophylactic medication and concerns about side effects. In addition to this,
      the likely health improvements TasP offers HIV-positive partners, as well as the
      attitude that the sick individual should be the first to receive HIV medication,
      also contributed to this conclusion. Issues of risk compensation were raised,
      with some HIV-negative partners indicating a desire to stop using condoms if ARV
      based prevention methods were available. CONCLUSIONS: Findings from the study
      indicate that TasP may represent a more viable approach to HIV prevention in
      Kenya than PrEP. Couples' preferences, however, may differ depending on local
      attitudes towards prophylaxis and health locus of control.

PMID- 25394071
TI  - Prevalence and European AIDS Clinical Society (EACS) criteria evaluation for
      proximal renal tubular dysfunction diagnosis in patients under antiretroviral
      therapy in routine setting.
AB  - INTRODUCTION: Tenofovir (TDF) is an antiretroviral drug often used in combination
      regimen in HIV-positive patients. Adverse effects affecting kidneys consist in an
      increase or a new onset proteinuria, a decrease of glomerular filtration rate
      (GFR), and/or a proximal renal tubular dysfunction (PRTD) that rarely leads to
      Fanconi's syndrome. EACS guidelines propose to screen PRTD in patients with
      chronic renal insufficiency, with a sudden decrease of eGFR, with
      hypophosphataemia (if non-renal causes such as vitamin D deficiency are excluded)
      and with a new onset proteinuria. We aim to evaluate the prevalence of PRTD by
      comparing the group of patients under TDF to the group free of TDF, in our cohort
      of 300 patients. We also aim to evaluate the accuracy of EACS criteria for
      screening PRTD in routine settings and to assess the utility of urinary samples
      in PRTD diagnosis. MATERIALS AND METHODS: During two consecutive years, we
      collected annually blood and urine samples at the same time in our outpatient
      clinic. We assessed kidney function, plasma levels and fractional excretion of
      phosphate, uric acid, potassium, plasma glucose and proteinuria. PRTD was defined
      by the presence of at least two out of the five following criteria: fractional
      excretion (FE) of phosphate >20% (or >10% when serum phosphate <0.8 mmol/L), non
      diabetic glycosuria (positive urine glucose with plasma glucose <70 mg/dL), renal
      tubular acidosis (urinary pH >5.5 and serum bicarbonate <21 mmol/L), uric acid FE
      >10% or potassium FE >10%. After the first year, patients with TDF regimen who
      were diagnosed with PRTD were shifted to TDF-free regimen and included again in
      the study. RESULTS: For PRTD (first line), they are expressed in number of
      diagnoses/total number of patients in this group. The second line resumes the
      number of PRTD diagnose patients who should have been screened according to EACS
      criteria. CONCLUSIONS: PRTD screening according to EACS criteria is not
      sufficient to diagnose every case, especially minor PRTD, mainly because the
      prevalence is low and its diagnosis remains difficult in routine settings. We
      recommend performing a urine test including proteinuria every year for patients
      undergoing TDF treatment. The next step will be to follow PRTD patients to
      evaluate the time laps until full recovery after TDF shift.

PMID- 25394072
TI  - The impact of tenofovir disoproxil fumarate on kidney function: four-year data
      from the HIV-infected outpatient cohort.
AB  - INTRODUCTION: With improvements in survival and disease progression in the era of
      combined antiretroviral therapy, complications such as kidney disease are
      becoming increasingly prevalent in HIV-infected patients. Tenofovir disoproxil
      fumarate (TDF) has been associated with nephrotoxicity, including decline in
      glomerular filtration rate, proximal tubular damage and acute kidney injury.
      OBJECTIVE: Characterize kidney safety of TDF-containing antiretroviral treatment
      (ART) regimens in HIV-infected patients. METHODS: Non-controlled, observational,
      retrospective study was based on the clinical files registry of HIV patients who
      started TDF between January and December 2008. We assessed outpatients followed
      at a single Portuguese center. Demographic, clinical, virological and
      immunological data at baseline were collected. Serum creatinine, estimated
      glomerular filtration rate (eGFR) and creatinine clearance (CrCL) were assessed
      at baseline, after six months and every year up to four years. CrCL and eGFR were
      calculated by Cockroft-Gault and Modification of Diet in Renal Disease equations,
      respectively. RESULTS: A total of 176 patients (71.6% males) with a mean age of
      43 years were enrolled. Ninety-six (52%) were ART-naive patients at TDF
      initiation. At baseline 12.5% had hypertension, 4% diabetes, 25% chronic
      hepatitis C and 9% chronic hepatitis B infections; 58% had normal renal function
      (eGFR >=90 ml/min/1.73 m(2)), 36% had mild (eGFR 60-89 ml/min/1.73 m(2)) renal
      dysfunction and 2.3% had moderate (eGFR 30-59 ml/min/1.73 m(2)) renal dysfunction
      at initiation of TDF. Eighty-three (47%) patients were on protease inhibitors and
      the remaining on NNRTIs containing regimens. During 48 months follow-up, 5%
      experienced moderate renal dysfunction and 1.7% severe renal dysfunction. Twenty
      one (12%) patients met the definition criteria of rapid decline of renal function
      (annual decline of eGFR >=3 ml/min/1.73 m(2) in two consecutive years). The
      development of kidney events was associated with age above 50 years, presence of
      comorbidities and advanced stage HIV infection (p>0.05 in univariate analysis).
      CONCLUSIONS: These data reveal a favourable renal safety profile of TDF, during a
      four-year follow-up. Screening for kidney disease markers, regular follow-up and
      control and prevention of risk factors for renal failure are crucial for adequate
      management of HIV-infected patients.

PMID- 25394073
TI  - Investigating presentations and outcomes of a joint HIV-renal clinic.
AB  - INTRODUCTION: HIV patients are at risk of renal dysfunction directly from HIV,
      indirectly from chronic inflammation as well as from antiretroviral drug
      toxicity. In particular, tenofovir (TDF) has been associated with proximal renal
      tubular dysfunction. A joint HIV-renal clinic was set up in 2009 to facilitate a
      timely review and minimize additional follow-up appointments. Brighton has a
      cohort of 2,150 HIV patients, 90% are on ARVs with 910/1,935 (47.0%) on regimens
      including TDF. This study aims to investigate the utility of this clinic and
      describe renal disease in this cohort. MATERIALS AND METHODS: Notes of patients
      scheduled for assessment at the clinic between 2012 and 2014 were reviewed.
      Demographics, HIV history, number of visits, reason for referral and outcome
      information were collected. RESULTS: Sixty-five patients, median age 51 years (28
      88) and median duration of HIV 163 months (20-335), were reviewed. Forty-two were
      taking TDF for a mean of 55.8 months (9-122). Forty-two patients were reviewed
      once with a median number of visits of 1 (1-4). CONCLUSIONS: TDF toxicity was the
      commonest reason for referral but only a minority (13.2%) needed to discontinue
      immediately. Optimizing BP control was the most frequent outcome suggesting this
      is an underappreciated cause for renal dysfunction amongst HIV physicians, as
      were other causes such as creatine and protein supplement usage. Running a "one
      stop-shop" clinic supports continuation of tenofovir in patients with
      proteinuria, and supports the diagnosis and management of poorly controlled
      hypertension and streamlines the management of these patients.

PMID- 25394074
TI  - Prevalence of low bone mineral density among HIV patients on long-term
      suppressive antiretroviral therapy in resource limited setting of western India.
AB  - INTRODUCTION: Bone mineral density (BMD) assessment in HIV patients is sparsely
      done in resource limited settings. MATERIALS AND METHODS: We conducted a cross
      sectional study of BMD amongst HIV patients following up in our clinic from 1
      June to 1 December 2013 by performing dual-energy X-ray absorptiometry scan
      (Lunar Prodigy Advanced DXA System, GE Healthcare) of lumbar spine and hip.
      Patients on long term (>=12 months), virologically suppressive antiretroviral
      therapy (ART) were included. Patients who were ART naive were included as control
      population. Virologic failures were excluded. Low BMD was defined by WHO T-score
      criteria (normal: T score >=-1;osteopenia: T score between -1 and -2.5 SD;
      osteoporosis: T score <=-2.5 SD). Baseline risk factors associated with low BMD
      like age, low BMI, lipoatrophy, diabetes mellitus, current smoking, current
      alcohol intake, steroid exposure and menopause were recorded. ART-related factors
      associated with low BMD like ART duration, exposure to tenofovir and exposure to
      protease inhibitors (PI) were studied. RESULTS: A total of 536 patients (66%
      males, 496 ART experienced and 40 ART naive) were included in this analysis.
      Median age was 42 years, mean BMI 23.35 kg/m(2) and median CD4 count 146
      cells/mm(3). All ART experienced patients had plasma viral load<400 copies/ml.
      CONCLUSIONS: Extremely high prevalence of accelerated BMD loss amongst ART naive
      and ART experienced patients in our cohort is a matter of deep concern due to its
      association with pathological fractures. Bone mineral loss was seen irrespective
      of ART used. Association of low BMD with low baseline CD4 count strengthens the
      case for early ART.

PMID- 25394075
TI  - No association between vitamin D deficiency and parathyroid hormone, bone density
      and bone turnover in a large cohort of HIV-infected men on tenofovir.
AB  - INTRODUCTION: Combination antiretroviral therapy (cART) may affect vitamin D
      [25(OH)D], parathyroid hormone (PTH), bone mineral density (BMD) and bone
      turnover (BT). Reduced BMD and secondary hyperparathyroidism have been reported
      with tenofovir (TDF). We investigated the associations between TDF and bone
      markers, especially in 25(OH)D-deficient patients. MATERIALS AND METHODS: In a
      single-centre longitudinal study investigating BMD in HIV-positive men, serum
      25(OH)D, calcium, phosphate, PTH and alkaline phosphatase (ALP) were measured.
      Lumbar spine, non-dominant total hip and non-dominant femoral neck BMD (g/cm(2))
      were measured using dual-energy X-ray absorptiometry. BT was assessed by serum
      type 1 procollagen (P1NP) and carboxy-terminal collagen cross-links (CTX). Mann
      Whitney U tests compared serum markers and BT, and t-tests compared BMD according
      to TDF in all and 25(OH)D-deficient patients. RESULTS: A total of 422 men were
      recruited: mean age 47 (SD 9.8) years, 94% white ethnicity, 93% MSM, diagnosed
      HIV positive for median 9.6 (IQR 5.0,15.5) years, median CD4 547 (IQR 411,696)
      cells/uL, HIV RNA <40 copies/mL in 87% (96% of those on cART). 25(OH)D (nmol/L)
      was normal (>75), insufficient (50-75), deficient (25-50) and severely deficient
      (<25) in 14%, 29%, 50% and 7%, respectively. Of 381 men on cART, 77% were
      currently on TDF. TDF was not associated with median calcium (p=0.69) or
      phosphate (p=0.52), but patients had higher (but normal) median ALP [81 (IQR
      69,103) vs. 73 (IQR 60,89) IU/L, p=0.005) compared to non-TDF cART. There was no
      difference in the association between vitamin D and PTH according to whether
      someone currently was (r=0.11, p=0.06, Figure 1) or was not using TDF (r=0.12,
      p=0.29, Figure 1). TDF was also not associated with PTH, BMD or BT in either all
      patients on cART (Table 1a) or in patients with 25(OH)D deficiency (Table 1b).
      CONCLUSIONS: In this largely TDF-experienced cohort of HIV-positive men, there
      was no association between TDF and 25(OH)D deficiency, hyperparathyroidism,
      reduced BMD or increased BT, although patients on TDF had higher but normal ALP.
      We found no evidence to support additional monitoring of bone markers in patients
      on TDF regardless of 25(OH)D status.

PMID- 25394076
TI  - Relationship between body mass index and bone mineral density in HIV-infected
      patients referred for DXA.
AB  - INTRODUCTION: Reduced bone mass density (BMD) is a frequent observation in HIV
      infected persons. Relationship between body mass index (BMI), weight, height and
      BMD was reported for many populations. In particular, BMI has been found to be
      inversely related to the risk of osteoporosis. METHODS: This is a cross
      sectional, monocentric study where all HIV-infected patients referred to first
      DXA scan in clinical routine during 2010-2013 were included. Osteopenia and
      osteoporosis were defined by T- score <-1 and <-2.5, respectively. Patients were
      categorized according to WHO BMI classification: underweight <18.5 kg/m(2);
      normal weight 18.5-24.9 kg/m(2); over weight 25-29.9 kg/m(2); obese >30 kg/m(2).
      Statistical analysis was carried using logistic regression. RESULTS: A total of
      918 patients were included: median age 49 years (IQR, 44-55); 59.4% male; 93%
      Caucasian. Median anthrometric characteristics were: 68 kg (IQR, 59-78); 1.7 m
      (IQR, 1.6-1.75); 23.5 kg/m(2) (IQR, 21.4-26.2). Underweight was found in 5%,
      normal weight in 61%, overweight in 26% and obesity in 8% of patients. According
      to T-scores, 110 (11.2%) patients were osteoporotic and 502 (54.7%) had
      osteopenia. In the femoral neck area, the prevalence of osteoporosis was slightly
      lower (5.7%) than lumbar spine site (9.2%). Agreements between sites of T-scores
      for the diagnosis of osteoporosis were 26 and 172 and 346 for osteopenia and
      normal BMD values, respectively. T-scores at femoral neck or lumbar spine
      positively correlated with BMI (p<0.001) (Figure 1). Among predictors of
      osteopenia/osteoporosis, univariable analysis showed: older age (p<0.0001); lower
      weight (p<0.0001); increasing height (p<0.002). Patients underweight had a higher
      risk of osteopenia (p=0.02) as well as of osteoporosis (p=0.003). Patients with
      BMI above normal had a reduced risk of low BMD (osteopenia p<0.0001; osteoporosis
      p<0.03). Controlling for calendar year, gender, ethnicity, and age, BMI was
      confirmed as risk factor if below normal (AdjOR of osteopenia 2.42 [95% CI 1.16
      5.07] p=0.02; AdjOR of osteoporosis 3.22 [95% CI 1.60-6.49] p=0.001).
      CONCLUSIONS: Our findings indicate that almost 66% of HIV-infected patients have
      subnormal bone mass. Further, as in other patient populations, in the HIV
      infection also low BMI is an important risk factor for osteopenia/osteoporosis.
      This finding highlights the compelling need for standardized screening actions,
      particularly in patients weighting below normal.

PMID- 25394077
TI  - Prevalence of osteoporosis and predictors of low BMD in a cohort of HIV-1
      infected patients in Rome: features of a population at high risk.
AB  - INTRODUCTION: Ageing of HIV-infected patients led to an increasing rate of
      osteopenia and osteoporosis. The cause is multifactorial, including virus
      activity, drug toxicity and host factors. The aim of our analysis is to quantify
      this issue according to our department experience and to evaluate predictors of
      low BMD. MATERIALS AND METHODS: HIV-1-infected patients, on stable HAART, were
      consecutively enrolled in this cross-sectional study and underwent DEXA. We
      analyzed the prevalence and evaluated predictors of low BMD in our population.
      RESULTS: We collected data from 208 patients, 148 of whom were male, with 49
      years median age (IQR 24.1-68.3). About 39% of patients were heterosexuals, 33.7
      MSM and 12.5% were IDU, 40.4% were smokers. Caucasians were 93.3%, and 13.9% were
      co-infected with HCV virus. Around 6.7% of patients were on their first HAART
      regimen and all of them started TDF. Their median time of HAART exposure was 1.17
      years (IQR 0.8-1.6). Conversely, median time of HAART exposure of multi
      experienced patients was 8.5 years (IQR 3.1-12.0). We stratified DEXA results for
      patients on first-line regimen versus multi-experienced one. We found that 42.9%
      of patients on first-line HAART had low BMD of lumbar spine and 7.1% had
      osteoporosis. Regarding the multi-experienced group of patients, lumbar spine
      osteopenia was observed in 36.6% of patients and 15.5% of them had osteoporosis.
      Median age of patients with low BMD of lumbar spine was 45.6 (IQR 24.1-68.3) for
      patients on first-line regimen and 49.8 years for multi-experienced (IQR 44.2
      54.0) regimen. We found similar data for BMD of hip, but no patients in the first
      group had hip osteoporosis. We also analyzed predictors of low BMD in our
      population. MSM patients showed a 3.4-fold higher risk to have osteoporosis of
      lumbar spine (OR 3.41, CI 1,105-9,269, p=0.03). As expected, we found that non
      Caucasian patients had 13.5-fold higher risk to have osteoporosis of the hip (OR
      13.52, CI 1.5-122.7, p=0.02). Exposure to HAART was also evaluated, but no
      predictors were found. CONCLUSIONS: Our data confirm how osteoporosis is highly
      prevalent and occurs earlier in HIV-infected patients. Antiretrovirals play a
      crucial role. In our experience loss of BMD can occur within a year of treatment,
      when almost half of our patients starting TDF had a low BMD. MSM patients have a
      higher risk to develop spine osteoporosis and non-Caucasian patients are more
      likely to have hip osteoporosis. We remark the importance of BMD assessment for
      HIV-infected patients especially during their first months of treatment.

PMID- 25394078
TI  - Co-administration of ritonavir-boosted protease inhibitors and rate of tenofovir
      discontinuation in clinical practice.
AB  - INTRODUCTION: In clinical trials, toxicity leading to discontinuation of
      tenofovir (TDF) is a rare occurrence (3% by two years)[1, 2]; however, in
      clinical practice it seems to be higher. Previous studies suggested that TDF
      toxicity is higher when it is co-administered with ritonavir-boosted protease
      inhibitors (PI/r)[3, 4]. The aim of this study is to assess the rate of TDF
      discontinuations in clinical practice and to explore associated factors. METHODS:
      All previously antiretroviral-naive patients initiating a TDF-containing regimen
      were selected from the ICONA cohort, unless they were positive for hepatitis B.
      The primary outcome was TDF discontinuation (>30 days) regardless of the reason,
      the secondary was TDF discontinuation due to toxicity. All analyses were repeated
      for the isolated stop of TDF (no stop of associated drugs). The main reason for
      discontinuation as reported by the treating physicians was used to classify
      stops. Kaplan-Meier (KM) analysis and Cox proportional hazards model were used.
      RESULTS: A total of 3,303 naive patients were enrolled: 674 (20.4%) were female,
      the median age was 38 years (32-45), 55% were on PI/r-based regimen and 45% on
      NNRTI; 80% of calculated estimated glomerular filtration rates (eGFR) were >90
      ml/min. The probability of discontinuation of TDF regardless of the reason was
      10% (95% CI 8-11) at two years, 20% by eight years. The causes of discontinuation
      were: toxicity (33%), failure (10%), non-adherence (21%), simplification (16%)
      and other/unknown causes (20%). The five-year KM estimates in the PI/r vs. not
      PI/r groups were 23% vs. 10%, respectively (log-rank p=0.0001), for the outcome
      of stopping regardless of the reason, and 8% vs. 4% (p=0.18) for discontinuation
      due to toxicity. In a multivariable Cox model, PI/r use and lower body weight
      were associated with increased risk of discontinuing TDF regardless of the
      reason; lower eGFR at baseline was associated with TDF discontinuation for
      toxicity and PI/r use was associated with isolated stop of TDF (Figure). No
      differences in rates of TDF discontinuations between PIs were found. CONCLUSION:
      In our cohort, the observed frequency of TDF discontinuations was low although
      higher than estimated in clinical trials (10% by two years). Co-administration of
      TDF with PI/r was associated with an increased rate of TDF discontinuations. This
      finding should guide further investigations of the mechanism that may have led to
      discontinuation of TDF in patients using PI/r.

PMID- 25394079
TI  - Acceptance rate of clinical study endpoints and adequacy of source documentation:
      experience from clinical study endpoint review in NEAT001/ANRS143.
AB  - INTRODUCTION: NEAT001/ANRS143 was an open-label, randomized, non-inferiority
      study comparing raltegravir+darunavir/r(RGV+DRV/r) vs.
      tenofovir/emtricitabine+darunavir/r (TDF/FTC+DRV/r) in HIV-infected
      antiretroviral naive adults. Primary efficacy outcome was a composite of
      virological and clinical events by week 96. MATERIALS AND METHODS: Clinical trial
      units collected and translated supporting documentation (SD) related to the
      investigator-reported events. A coordinator checked events and SD for consistency
      and completeness. The Endpoint Review Committee (ERC) determined if clinical
      events met pre-defined diagnostic criteria in categories "confirmed" or
      "probable". The ERC of 12 experienced, independent clinicians served in groups of
      three conducting individual reviews in writing, blinded to treatment arm.
      Differences of opinion were adjudicated in a second review by direct dialogue
      between reviewers. "Confirmed" events required adequate SD like laboratory,
      radiographic or pathology diagnostic reports. "Probable" events were typically
      based on clinical criteria. RESULTS: Of the 164 serious and 3,964 adverse events
      reported in the study, 133 qualified for endpoint review, for a total of 153
      adjudications: CONCLUSIONS: Blinded endpoint review prevented unacceptably high
      false positive event rates documenting that real-time ascertainment of clinical
      endpoints is crucial for appropriateness of the overall results. Non-confirmed
      events jeopardize the statistical power in this and probably all kinds of
      clinical studies. The rejection rate was not indicative of poor study conduct -
      on the contrary over-reporting prevented missing events, which would have
      adversely impacted the trial. Adequacy of SD and investigator training on
      possible differences in event criteria in daily pragmatic clinical management
      compared to protocol defined criteria is essential.

PMID- 25394080
TI  - Safety of darunavir/ritonavir (DRV/r) in HIV-1-infected DRV/r-experienced and 
      naive patients: analysis of data in the real-world setting in Italy.
AB  - INTRODUCTION: This descriptive, non-interventional study on HIV-1-infected
      patients treated with DRV/r in the usual clinical setting, with a single-arm
      prospective observational design, collected data on utilization of
      darunavir/ritonavir (DRV/r) under the conditions described in marketing
      authorization in usual clinical practice in Italy to evaluate efficacy and safety
      of DRV/r-based antiretroviral (ARV) treatment. This analysis focussed on the
      safety profile of DRV/r in HIV-1 infected patients. MATERIALS AND METHODS: Data
      were analyzed from four cohorts of HIV-1-infected patients treated with DRV/r in
      the real-world setting, including an ARV-naive-DRV/r-naive cohort (Cohort 1), an
      ARV-experienced-DRV/r-naive cohort (Cohort 2) and two ARV-DRV/r-experienced
      cohorts (Cohorts 3 and 4), one of which (Cohort 3) was from the DRV/r Early
      Access Program. The objective of this analysis was to examine the safety data
      obtained in these four cohorts in patients enrolled from June 2009 to November
      2011 and observed until December 2012 or DRV/r discontinuation. RESULTS: Safety
      data from 875 patients were analyzed. DRV/r-based treatment was well tolerated,
      with 36.2% of patients reporting >=1 adverse event (AE) and very few
      discontinuations due to study drug-related AEs (3.0% overall). The most frequent
      AEs were diarrhoea (2.7%), reduced bone density (2.6%) and hypercholesterolaemia
      (2.1%) (Table 1). Regarding metabolic parameters, levels of liver enzymes alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) remained stable from
      baseline to the last study visit (LSV) in DRV-experienced patients and decreased
      in DRV-naive patients. Blood glucose concentrations remained stable in all
      cohorts. Serum triglyceride and cholesterol concentrations remained stable in DRV
      experienced patients but increased in naive patients, yet were still within
      normal range. CONCLUSIONS: In HIV-1-infected patients treated with DRV/r in these
      settings, the tolerability profile was favourable and similar to (or better than)
      that reported in controlled clinical trials. These data confirm DRV/r to be a
      safe treatment choice in DRV/r-experienced and naive patients.

PMID- 25394081
TI  - Efficacy and safety of etravirine-containing regimens in a large cohort of
      HIV/HCV coinfected patients according to liver fibrosis.
AB  - INTRODUCTION: Etravirine has become an alternative in HIV/HCV coinfected patients
      because of safety and lack of interactions with anti-HCV drugs. The aim of this
      study was to establish the risk of liver toxicity in HIV/HCV coinfected patients
      receiving etravirine in the clinical setting, according to the degree of liver
      fibrosis and different accompanying drugs. MATERIAL AND METHODS: Cohort study of
      211 patients initiating etravirine as part of their antiretroviral regimen. HCV
      coinfection was defined as a positive RNA-HCV, whereas baseline liver fibrosis
      was assessed by transient elastography at baseline. Hepatotoxicity was defined as
      an increased AST/ALT, 5-fold higher over upper, normal limits for patients with
      normal baseline values, or 3.5-fold if altered at baseline. RESULTS: HCV
      coinfection was observed in 145 patients (69%) with a longer time of HIV
      infection and time on HAART than mono-infected patients, and a lower nadir (182
      vs 227 cells/mL; p=0.02) and baseline CD4+ count (446 vs 552 cells/mL; p=0.02).
      Etravirine was used with two nucleoside analogues in 62%, with boosted darunavir
      in 17%, with raltegravir in 10%, and with darunavir plus raltegravir or maraviroc
      in 10% of patients without differences according to HCV serostatus. Transient
      elastography in 117 patients performed at etravirine initiation (median, 33 days)
      showed fibrosis 1 and fibrosis 4 in 37% and 24% of cases, and median stiffness
      value was 8.25 kPa (3.5-69). During an accumulated follow-up of 449.3 patient
      years (median, 611 days), only one coinfected patient with fibrosis 4 (stiffness
      value, 50.1 kPa), receiving a rescue regimen including darunavir/r plus maraviroc
      plus two nucleoside analogues, developed a grade 3-4 of liver toxicity (0.5%).
      There were no other episodes of liver toxicity, as defined, and only 6 (3%) and 9
      patients (4%) had a grade 1 and 2 of toxicity, respectively, in most cases
      related to HCV coinfection (6 and 6 cases). Moreover, HCV coinfection or advanced
      fibrosis was not associated to a higher risk of etravirine discontinuation (26%
      vs 21%; p=0.27, log-rank test) or virologic failure (9% vs 11%, p=0.56). CD4+
      cell count increase was lower in HCV patients (+23 vs +86 at 6 month; p=0.02).
      CONCLUSIONS: Etravirine is safe in HIV/HCV coinfected patients, even in presence
      of moderate and advanced liver fibrosis and as part of different antiretroviral
      regimens.

PMID- 25394082
TI  - Sex differences in apolipoprotein A1 and nevirapine-induced toxicity.
AB  - Nevirapine (NVP) is associated with severe liver and skin toxicity through
      sulfotransferase (SULT) bioactivation of the phase I metabolite 12-hydroxy-NVP [1
      3]. The female sex, a well-known risk factor for NVP-induced toxicity, is
      associated with higher SULT expression (4) and lower plasma levels of 12-hydroxy
      NVP [3]. Interestingly, apolipoprotein A1 (ApoA1) increases SULT2B1 activity and
      ApoA1 synthesis is increased by NVP [5, 6]. Herein, we explore the effect of
      ApoA1 levels on NVP metabolism and liver function. The study protocol was firstly
      approved by the hospitals' Ethics Committees. All included individuals were HIV
      infected patients treated with NVP for at least one month. The plasma
      concentrations of NVP and its phase I metabolites were quantified by HPLC [7].
      ApoA1 levels were assessed by an immunoturbidimetric assay. Forty-nine HIV
      infected patients on NVP were included (53% men, 59% Caucasian). NVP plasma
      levels were correlated with HDL-cholesterol (Spearman r=0.2631; p=0.0441) and
      ApoA1 (Spearman r=0.3907; p=0.0115). Women had higher ApoA1 levels than men
      (Student's t Test; p=0.0051). In both sexes, 12-hydroxy-NVP levels were
      negatively correlated with ApoA1 (male: Spearman r=-0.3810; p=0.0499 female:
      Spearman r=-0.5944; p=0.0415). In men, ApoA1 was positively correlated with
      aspartate aminotransferase (AST, Spearman r=0.5507; p=0.0413), while in women
      ApoA1 was associated (Spearman r=0.6408; p=0.0056) with alanine aminotransferase
      (ALT). These results show sex differences in NVP-induced ApoA1 synthesis. The
      higher ApoA1 levels in women might stabilize SULT2B1 [6]. This would explain the
      lower levels of 12-hydroxy-NVP [3] and the higher hepatotoxicity found in women,
      due to increased sulfonation of this metabolite. These data support a role for
      ApoA1 in the sex dimorphic mechanism leading to NVP-induced toxicity. 

PMID- 25394083
TI  - Prevalence and risk factors of sleep disturbances in a large HIV-infected adult
      population.
AB  - INTRODUCTION: Sleep disturbances are frequently reported in HIV-infected patients
      but there is a lack of large studies on prevalence and risk factors, particularly
      in the context of current improved immuno-clinical status and use of the newest
      antiretrovirals (ARV). METHOD: Cross-sectional study to evaluate the prevalence
      and factors associated with sleep disturbance in adult HIV-infected patients in
      six French centres of the region "Pays de la Loire". Patients filled a self
      administered questionnaire on their health behaviour, sleep attitudes (Pittsburgh
      Sleep Quality Index PSQI), quality of life (WHO QOL HIV BREF questionnaire) and
      depression (Beck depression Inventory (BDI)-II questionnaire). Socio-demographic
      and immunovirologic data, medical history, ARVs were collected. RESULTS: From
      November 2012 to May 2013, 1354 consecutive non-selected patients were enrolled.
      Patients' characteristics were: 73.5% male, median age 47 years, active
      employment 56.7%, France-native 83% and Africa-native 14.7%, CDC stage C 21%,
      hepatitis co-infection 13%, lipodystrophy 11.8%, dyslipidemia 20%, high BP 15.1%,
      diabetes 3%, tobacco smokers 39%, marijuana and cocaine users, 11.7% and 1.7%
      respectively, and excessive alcohol drinkers 9%. Median (med) duration of HIV
      infection was 12.4 years, med CD4 count was 604/mm(3); 94% of Patients were on
      ARVs, 87% had undetectable viral load. Median sleeping time was 7 hours. Sleep
      disturbances (defined as PSQI score >5) were observed in 47% of the patients,
      more frequently in female (56.4%) than in male (43.9%) (p<0.05) and moderate to
      serious depressive symptoms (BDI score>19) in 19.7% of the patients. In
      multivariate analysis, factors associated with sleep disturbances (p<0.05) were
      depression (odds ratio [OR] 4.6; 95% confidence interval [CI] 3.2-6.8), male
      gender (OR 0.7; CI 0.5-0.9), active employment (OR 0.7; CI 0.5-0.9), living
      single (OR 1.5; CI 1.2-2.0), tobacco-smoking (OR 1.3; CI 1.0-1.8), duration of
      HIV infection (>10 vs. <10 y.) (OR 1.5; CI 1.1-2.0), ARV regimen containing
      nevirapine (OR 0.7; CI 0.5-0.9) or efavirenz (OR 0.5; CI 0.3-0.7). CONCLUSIONS:
      Prevalence of sleep disturbances is high in this HIV population and roughly
      similar to the French population. Associated factors are rather related to social
      and psychological status than HIV infection. Depression is frequent and should be
      taken in care to improve sleep quality.

PMID- 25394084
TI  - Proton 1H- and Phosphorus 31P-MR spectroscopy (MRS) in asymptomatic HIV-positive
      patients.
AB  - INTRODUCTION: HIV infection is accompanied by a variety of neurological
      disorders. Depression of cell-mediated immunity is followed by the development of
      central nervous system opportunistic infections/tumours, and frequently by the
      occurrence of the AIDS dementia complex (ADC). However, the pathophysiology of
      the emergence of neuro-AIDS is still unknown. Despite the development of
      cognitive impairments, the early diagnosis, objectification and quantification of
      the existence and extent of this impairment during infection are difficult to
      recognize in each individual case. To support the early diagnosis of ADC, there
      is a need for additional, non-invasive diagnostic methods. In this study, it is
      of interest to answer the clinically relevant question of whether magnetic
      resonance spectroscopy can detect changes in the cerebral metabolism of
      asymptomatic HIV-positive patients and is possibly suitable for the early
      diagnosis and prevention of HIV encephalopathy. METHODS: A group of 13
      asymptomatic, HIV-positive patients with combined antiretroviral therapy (cART)
      and 13 healthy controls were examined with 2D 1H-MRS and 3D 31P-MRS at 3T. The
      patients were treated with cART for at least 12 months. Changes in the absolute
      concentrations of phosphorylated metabolites (ATP), N-acetyl-aspartate, creatine,
      myo-Isonitol, glutamate/glutamine and choline-containing compounds were compared
      with that of control subjects. RESULTS: Asymptomatic HIV-positive patients had
      significantly lower N-acetyl-aspartate in the white matter in a frontal and
      parietal target region. The other evaluated metabolites in the 1H MRS showed no
      significant difference between the HIV-positive patients and healthy controls.
      The 31P-MRS detected significant elevated values regarding the choline-containing
      compounds PEth, GPE and PCho. CONCLUSIONS: This spectroscopic study revealed a
      significantly lower N-acetyl-aspartate in the white matter in a frontal and
      parietal cerebral target region in asymptomatic, HIV-positive patients as an
      early sign of neuronal disintegration. The 31P-MRS detected significant elevated
      values regarding the choline-containing compounds PEth, GPE and PCho as an early
      sign of gliosis. Furthermore we could show that with the use of 1H-MRS and 31P
      MRS cerebral metabolites can be reliably detected and measured in HIV-positive
      patients. The 1H-MRS and 31P-MRS is therefore suited as a diagnostic tool for
      early cerebral metabolic changes in HIV-positive patients.

PMID- 25394085
TI  - Cerebral volumes, neuronal integrity and brain inflammation measured by MRI in
      patients receiving PI monotherapy or triple therapy.
AB  - INTRODUCTION: Penetration of protease inhibitors (PI) in the central nervous
      system (CNS) is limited. Therefore, there are concerns about the capacity of PI
      monotherapy (MT) to control HIV in CNS and preserve brain integrity. METHODS:
      Exploratory case-control study designed to compare neuronal integrity and brain
      inflammation in HIV-suppressed patients (>2 years) with and without
      neurocognitive impairment (NI), treated with MT or triple therapy (TT), 3-Tesla
      cerebral magnetic resonance image (MRI) and spectroscopy (MRS) were used to
      evaluate neuronal integrity (volume of cerebral structures and MRS levels of N
      acetyl-aspartate (NAA)) and brain inflammation (MRS levels of myo-inositol (MI)
      and choline (CHO)). MRS biomarkers were measured in 4 voxels located in basal
      ganglia, frontal (2) and parietal lobes. A comprehensive battery of tests (14
      tests - 7 domains) was used to diagnose neurocognitive impairment (1). RESULTS:
      We included 18 neurocognitively impaired patients (MT: 10, TT: 8) and 21 without
      NI (MT: 9; TT: 12, Table 1). Subset of patients with NI: cerebral volumes and MRS
      biomarkers were mostly similar between MT and TT with exception of the right
      cingulate nucleolus volume (MT: 8854+/-1851 vs TT: 10482+/-1107 mm(3); p<0.04),
      CHO levels in basal ganglia (MT: 0.44+/-0.05 vs TT: 0.37+/-0.03 MMOL/L; p<0.01)
      and the NAA levels in parietal lobe (MT: 1.49+/-0.12 vs 1.70+/-0.13 MMOL/L;
      p<0.01). Subset of patients without NI: cerebral volumes and MRS biomarkers were
      mostly similar between MT and TT with exception of MI levels in frontal lobe (MT:
      1.20+/-0.36 vs 0.81+/-0.25 MMOL/L; p=0.01). CONCLUSIONS: We did not find
      significant differences in cerebral volumes or MRS biomarkers in most areas of
      the brain. However, we found higher levels of inflammation and neuronal damage in
      some brain areas of patients who received MT. This observation has to be taken
      into caution while we could not adjust our results by potential confounders.
      Further investigation is needed to confirm these preliminary results.

PMID- 25394086
TI  - Clinical significance of the UGT1A1*28 allele detection in HIV-infected patients.
AB  - INTRODUCTION: The UGT1A1*28 (rs8175347) polymorphism is associated with
      hyperbilirubinemia. The presence of 6 TA-repeats in the UGT1A1 gene promoter
      region corresponds to normal UGT1TA1 activity. A detection of 7 TA-repeats in
      hetero- or homozygous individuals [(TA)6/(TA)7 and (TA)7/(TA)7] is associated
      with lower UGT1TA1 activity, which may eventually result in the development of
      Gilbert syndrome and/or modified individual response to drugs metabolized by this
      enzyme. ATV contributes to the decreased levels of UGT1A1, which may lead to
      elevations of indirect bilirubin, jaundice and even to therapy discontinuation.
      We evaluated the prevalence of the UGT1A1*28 among HIV-infected patients and the
      dependence of the frequency and severity of AE during ATV treatment on individual
      genetic characteristics. MATERIALS AND METHODS: 47 HIV-infected patients was
      screen for UGT1A1 genotype and the presence of UGT1A1*28. All patients received
      ATV in the HAART regimen for 48 weeks. Changes in the total, direct and indirect
      bilirubin, ALT, AST, GGT and jaundice were evaluated. Statistical analysis was
      performed using Microsoft Office Excel for Windows XP Professional 2007 and
      Biostat. RESULTS: All patients were followed up in the AIDS Center (males 72.3%,
      median age 33 years, median CD4+ count-282 cells/ul (19.5%)). HBV/HCV was in
      36.2% patients. Ten patients had risk factors that could affect bilirubin
      turnover (chronic cholecystitis, biliary dyskinesia, etc.). Genotype (TA)6/(TA)6
      was found in 42.6% patients, (TA)6/(TA)7-42.6% and (TA)7/(TA)7-14.9%. Overall
      prevalence of UGT1A1*28 was 57.4%, and homozygous allele frequency was 14.9%.
      G3/4 of indirect bilirubin were detected in 36.2% patients [(TA)6/(TA)6 in 10
      20%, (TA)6/(TA)7-25-40%, (TA)7/(TA)7-72-86%], and significant jaundice in 10.6%
      [80% with (TA)7/(TA)7]. The OR for hyperbilirubinemia>40 umol/L in patients with
      heterozygous UGT1A1*28 was increased 3 times over patients without this allele
      (OR 3.07, 95% CI 1.54-4.6) and 34 times as compared with homozygotes (OR 33.9,
      95% CI 31.45-36.35). The presence of additional risk factors increased the
      probability of G3/4 hyperbilirubinemia. No significant changes in the ALT, AST,
      and GGT levels were observed. CONCLUSIONS: The risk of severe hyperbilirubinemia
      during ATV treatment is minimal for patients without UGT1A1*28 and no more than
      one additional risk factor and for patients with UGT1A1*28 and no additional risk
      factors; patients with homozygous genotype UGT1A1*28 are at the highest risk.

PMID- 25394087
TI  - Safety of rilpivirine plus nucleoside reverse-transcriptase inhibitors in HIV
      infected Taiwanese with a higher prevalence of hepatitis virus infection.
AB  - INTRODUCTION: Combination antiretroviral therapy (cART) containing rilpivirine
      plus 2 NRTIs are effective antiretroviral (ARV) regimens for ARV-naive HIV
      infected patients who had baseline plasma HIV RNA load (PVL) <5 log10 copies/mL
      and as switch therapy for those with viral suppression. In this study, we aimed
      to assess the short-term safety of rilpivirine-containing regimens among HIV
      infected patients who initiated or switched to rilpivirine plus two NRTIs in
      Taiwan. MATERIALS AND METHODS: Between January and June 2014, medical records of
      all HIV-infected patients who initiated or switched to rilpivirine plus two
      NRTIs, during the follow-up were reviewed to assess the tolerance and adverse
      effects. Using a standardized data collection form, we recorded data of PVL and
      CD4 count, serologies for hepatitis B and C virus (HBV and HCV, respectively),
      haemogram, aminotransferases, bilirubin and serum creatinine before starting
      rilpivirine-containing regimens at four weeks and every 12 weeks thereafter.
      RESULTS: During the study period, medical records of 246 patients initiated their
      first ARV therapy with rilpivirine-containing regimens (n=90) or switched to
      rilpivirine-containing regimen from other regimens (156). Of the 246 patients,
      73.4% were men who have sex with men and 9.1% and 25.6% tested positive for HBsAg
      and anti-HCV antibody, respectively. Baseline CD4 was 395 cells/mm(3) (range, 2
      1581) and PVL, 2.76 log10 copies/mL (range, <1.3>7.0 log10 copies/mL). As of 10
      July, 23 patients (9.3%) stopped rilpivirine-containing regimens due to
      gastrointestinal upset (n=4), skin rash (2), depression (2), poor sleep (3),
      anaemia (4, all being with zidovudine/lamivudine), nail hyperpigmentation (1),
      presence of transmitted drug resistance (4), and elevated aminotransferase levels
      (1). The proportion of the patients with aminotransferases of fivefold or higher
      than the upper limit of normal (ULN) was 1.7% and 1.5% for AST and ALT,
      respectively, before starting rilpivirine-containing regimens; the respective
      value was 1.4% and 2.4% after 12 weeks of cART. CONCLUSIONS: Rilpivirine
      containing regimens were generally well tolerated and less than 10% of the
      patients had to stop rilpivirine due to various reasons. Despite a higher
      prevalence of chronic HBV or HCV infection, rilpivirine-containing regimens did
      not cause significant changes of aminotransferases from baseline.

PMID- 25394088
TI  - Quality of life of people living with HIV, preliminary results from IANUA
      (Investigation on Antiretroviral Therapy) study.
AB  - INTRODUCTION: The introduction of combined antiretroviral treatment (cART) has
      reduced HIV-associated morbidity and mortality, and changed the patients'
      perspective of life. As a result, Health Related Quality of Life (HRQOL) has
      become a crucial clinical issue. OBJECTIVE: Assessment of HRQOL in a sample of
      Italian patients from IANUA study. Investigate correlation between CD4 cell
      counts, viral load and changes in HRQOL. MATERIALS AND METHODS: EQ-5D-3L self
      reported questionnaire has been used in the evaluation of HRQOL. It assesses five
      dimensions: "mobility," "self care," "usual activities," "pain/discomfort" and
      "anxiety/depression." Each dimension has three levels: no problems, some problems
      and extreme problems. In addition, it includes a Visual Analogue Scale (VAS)
      where one's own health "today" is rated from 0 "worst imaginable health" to 100
      "best imaginable health." The respondents provide information on marital status,
      education, employment/unemployment, other treatments used in addition to HAART
      (1,2,3,4,5 or more) and number of hospitalizations due to HIV/AIDS. RESULTS: 684
      patients completed the questionnaire: 231 females and 453 males. The mean age of
      the sample was 51 years (range 21-78). The mean VAS score was 69.9. 558 patients
      (81.5%) reported no problems in mobility. 642 patients (93.5%) had no problems in
      self care. 423 patients (61.8%) had no pain/discomfort while 219 had some
      problems. 326 patients (46.1%) had some problems in anxiety/depression.
      CONCLUSIONS: The analysis of self-reported questionnaires indicates that HRQOL in
      our sample group is not deeply affected by HIV/AIDS. The dimensions that are
      affected in the least are "mobility" and "self care" while the major problem is
      "anxiety/depression" with half of the sample reporting moderate or high level.

PMID- 25394089
TI  - Should the dose of tenofovir be reduced to 200-250 mg/day, when combined with
      protease inhibitors?
AB  - INTRODUCTION: The approved dose of tenofovir disproxil fumarate, 300 mg once
      daily, was established in clinical trials in combination with efavirenz, which
      does not significantly affect tenofovir concentrations. Combining tenofovir with
      lopinavir/r, darunavir/r or atazanavir/r increases tenofovir concentrations,
      which could raise the risk of renal adverse events. Newly approved tenofovir
      tablets are available at lower strength (200 or 250 mg) for use in paediatrics.
      METHODS: A literature search was used to assess the effects of lopinavir/r,
      darunavir/r and atazanavir/r on tenofovir plasma Cmax, AUC and Cmin (Geometric
      Mean Ratio and 90% confidence intervals). Assuming linear dose-proportional
      pharmacokinetics (as observed in dose-ranging studies), the 250 mg tablet was
      predicted to achieve plasma concentrations 17% lower than the 300 mg dose, and
      the 200 mg tablet to achieve plasma levels 33% lower. Effects on tenofovir plasma
      Cmax, AUC and Cmin concentrations were assessed for combined dosing of each
      protease inhibitor with 250 or 200 mg daily doses of tenofovir, versus standard
      dose tenofovir (300 mg daily) without protease inhibitors. RESULTS: In drug-drug
      interaction studies, lopinavir/ritonavir significantly increased tenofovir Cmax,
      AUC and Cmin. Effects of each PI on tenofovir Cmin were greater than effects on
      Cmax or AUC. Using a 250 mg paediatric dose of tenofovir with
      lopinavir/ritonavir, tenofovir Cmin was predicted to remain higher than tenofovir
      300 mg used with efavirenz (GMR=1.26, 95% CI 1.14-1.38). Similar results were
      observed for use of tenofovir 250 mg with atazanavir/ritonavir (GMR=1.07, 95% CI
      1.01-1.13) and with darunavir/ritonavir (GMR=1.14, 95% CI 0.99-1.31). Predicted
      tenofovir AUC levels for the 250 mg dose with protease inhibitors were all within
      the bioequivalence range, relative to use with efavirenz. Using a 200 mg
      paediatric dose of tenofovir with lopinavir/ritonavir, the tenofovir Cmin was
      predicted to be bioequivalent to tenofovir 300 mg used with efavirenz (GMR=1.02,
      95% CI 0.92-1.11). Similar results were observed for use of tenofovir 200 mg with
      atazanavir/ritonavir (GMR=0.86, 95% CI 0.82-0.91) and with darunavir/ritonavir
      (GMR=0.92, 95% CI 0.80-1.05). All three results were within the bioequivalence
      limits of 0.8-1.25. CONCLUSIONS: Use of approved paediatric doses of tenofovir
      (200-250 mg once daily) in combination with lopinavir/r,darunavir/r or
      atazanavir/r could compensate for known drug interactions. This dose modification
      could potentially improve renal safety.

PMID- 25394090
TI  - The effect of dolutegravir on the pharmacokinetics of metformin in healthy
      subjects.
AB  - INTRODUCTION: Dolutegravir (DTG) is an HIV integrase strand transfer inhibitor
      approved for use in combination with other antiretrovirals for the treatment of
      HIV-infection in adults and adolescents. Metformin is a drug frequently used in
      diabetic HIV-infected patients, which requires titration to optimize dosing. In
      vitro, DTG inhibits organic cation transporter 2 (OCT2) and multidrug and toxin
      extrusion transporter 1 (MATE 1) which are known to be involved in the
      disposition of metformin. The objective of this study was to assess the drug
      interaction between DTG and metformin. MATERIALS AND METHODS: This was an open
      label, parallel-group, three-period crossover study in healthy adult subjects.
      Eligible subjects were enrolled into one of the two treatment cohorts (15
      subjects/cohort). Subjects received metformin 500 mg q12h for 5 days in Period 1;
      metformin 500 mg q12h plus DTG 50 mg q24h (Cohort 1) or 50 mg q12h (Cohort 2) for
      7 days in Period 2; and metformin 500 mg q12h for 10 days in Period 3. There were
      no washout periods between treatments. All doses of study drug were taken with a
      moderate-fat meal. Serial plasma PK samples and safety assessments were obtained
      throughout the study. Non-compartmental PK analysis was performed and geometric
      least squares (GLS) mean ratios and 90% confidence intervals (CI) were generated
      by the mixed effect model for within-subject treatment comparisons for each
      cohort. RESULTS: Fourteen and thirteen subjects completed study in Cohort 1 and
      Cohort 2, respectively. Plasma exposures of metformin were significantly
      increased when co-administered with DTG (Table 1). CONCLUSIONS: Co-administration
      of DTG and metformin was well tolerated, yet significantly increased metformin
      plasma exposure; effects were DTG dose dependent. Though metformin has a wide
      therapeutic index and alone is not associated with hypoglycemia, close monitoring
      is recommended when co-administering metformin and DTG. Dose adjustments of
      metformin may be considered.

PMID- 25394091
TI  - Low isoniazid and rifampicin concentrations in TB/HIV co-infected patients in
      Uganda.
AB  - INTRODUCTION: There is limited data available on exposure to anti-tuberculosis
      (TB) drugs in this region. Peloquin has described reference ranges [1] however
      some studies have demonstrated that patients actually achieve concentrations
      below these ranges [2]. There is limited data about exposure to anti-TB drugs in
      the HIV/TB co-infected population in Sub-Saharan Africa. Our objective is to
      describe the concentration of anti-TB drug levels in a well characterized
      prospective cohort of adult patients starting treatment for pulmonary TB.
      METHODS: This study is an ongoing study carried out in the TB/HIV integrated
      clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture
      and microscopy was done for all patients. We performed pharmacokinetic blood
      sampling of anti-TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8
      weeks and 24 weeks after initiation of anti-TB treatment using ultraviolet high
      performance liquid chromatography (UV-HPLC). We described the maximum
      concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and
      pyrazinamide (Z) and compare them with the values observed by Peloquin et al.
      referenced in other studies. RESULTS: We started 113 HIV infected adults on a
      fixed dose combination of HREZ. The median age of our population was 33 years, of
      which 52% were male with a median BMI of 19 kg/m(2) and a median CD4 cell count
      of 142 cells/uL. In 90% of the participants, the diagnosis of TB was based on
      microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H
      and R. CONCLUSION: We observed lower concentrations of isoniazid and rifampicin
      in our study population of HIV/TB co-infected patients. The implications of these
      findings are not yet clear. We therefore need to correlate our findings with the
      response to TB treatment.

PMID- 25394092
TI  - Simulation of the impact of rifampicin on darunavir/ritonavir PK and dose
      adjustment strategies in HIV-infected patients: a population PK approach.
AB  - INTRODUCTION: Treatment of HIV/TB co-infection is challenging due to high drug
      drug interaction potential between antiretrovirals and rifamycins, such as
      rifampicin (RIF). The PK interaction between darunavir/ritonavir (DRV/RTV) and
      RIF has not been studied. Utilizing other protease inhibitor data, population PK
      modelling and simulation was applied to assess the impact of RIF on DRV/RTV PK
      and generate alternative dosing strategies to aid future clinical trial design.
      MATERIALS AND METHODS: A previously developed model describing DRV/RTV PK
      including data from three studies in HIV patients was used [n=51, 7 female,
      DRV/RTV 800/100 mg (n=32) or 900/100 mg once daily (qd; n=19) (1). The PK
      interaction between DRV/RTV and RIF was assumed to mimic that observed in HIV
      infected, TB negative patients receiving lopinavir (LPV)/RTV (n=21) (2).
      Simulations of DRV/RTV 800/100 mg qd (n=1000) were performed (-RIF). The model
      was adapted to increase the typical value of apparent oral clearance (CL/F) by
      71% and 36% and decrease relative bioavailability (F) by 20% and 45% for DRV and
      RTV, respectively (2); 1000 simulations were generated (+RIF). Dose adjustments
      of DRV/RTV 1200/200 mg qd, 800/100 mg and 1200/150 mg twice daily (bid) were
      simulated to overcome the interaction. DRV trough (Ctrough) for each dosing
      scenario was compared to the reference (-RIF) by GMR (90% CI). RESULTS: DRV and
      RTV were described by a 1 and 2-compartment model, respectively. A maximum effect
      model, with RTV inhibiting DRV CL/F, best described the relationship between the
      drugs. Compared to the reference (-RIF), simulated DRV Ctrough was 70%, 46% and
      20% lower for 800/100 mg qd, 1200/200 mg qd and 800/100 mg bid all +RIF,
      respectively. Ctrough was 38% higher with 1200/150 mg bid +RIF (Table 1).
      CONCLUSIONS: Modelling and simulation was used to investigate the theoretical
      impact of RIF on DRV/RTV PK. Based on simulations, 800/100 mg and 1200/150 mg
      both bid could largely overcome the impact of the interaction. However, the risk
      of increased RTV-related side effects and higher pill burden should be
      considered. In vitro work is ongoing to develop a physiologically based model
      characterizing the interaction and informing simulations.

PMID- 25394093
TI  - CSF LPV concentrations and viral load in viral suppressed patients on LPV/r
      monotherapy given once daily.
AB  - INTRODUCTION: Plasma trough concentrations of lopinavir (LPV) given as LPV/r
      800/200 mg once daily (OD) are reduced in comparison with 400/100 mg twice daily
      (BID). While OD dosage of LPV/r is sufficient to achieve viral suppression in
      plasma, data about drug penetration and viral suppression in central nervous
      system (CNS) is needed, mainly if LPVr is used as maintenance monotherapy
      strategy in selected patients. The objective of this study was to evaluate CSF
      HIV-1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD
      (LPVrMOD). MATERIAL AND METHODS: This is a cross-sectional sub-study within a
      prospective, open-label pilot simplification study to evaluate the efficacy and
      safety of LPV/rMOD in virologically suppressed patients previously receiving a
      BID LPV/r monotherapy regimen (LPV/rMBID), the "Kmon study" (NCT01581853). To
      assess LPV concentrations and HIV-1 RNA in CSF, a lumbar puncture (LP) was
      performed in a subgroup of patients after at least one month of LPVrMOD
      treatment. Plasma-paired samples of all patients were also obtained. HIV-1 RNA
      was determined by real-time PCR (limit of detection 40 copies/mL). Liquid
      chromatography-tandem mass spectrometry (Tandem labs, NJ) was used to determine
      CSF and blood plasma LPV concentrations. RESULTS: Nine patients were included.
      Median (range) age was 48 (34-56) years, median CD4 cell count 672 (252-1,408)
      cells/mL, median nadir CD4 count 125 (35-537) cells/mL and 40% of subjects were
      HCV-positive. Before starting LPV/rMOD median time on a LPV/r-containing regimen
      and on LPV/rMBID were 9 (4-11) years and 15 (7-24) months respectively, median
      time with undetectable HIV viral load was 5 (3-12) years and 2 patients had a
      previous documented blip. LP was performed a median of 24 (8-36) weeks after
      starting LPV/rMOD and 24 (11-28) hours after the last LPV/rMOD dose CSF and
      plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was
      9.78 (1.93-78.3) ng/mL, median LPV plasma concentration 1,103 (377-16,700) ng/mL
      and median LPV CSF/plasma ratio 0.3% (0.1-1.2). CONCLUSIONS: No CSF viral escape
      was detected and LPV concentrations were above the IC50 for wtHIV-1 (1.9 ng/mL).
      However, as concentrations were close to IC50 in some patients, a careful
      clinical follow up of patients receiving this regimen would be advisable. Larger
      longitudinal studies will be helpful for a better understanding of the CNS
      antiviral activity of LPVr monotherapy.

PMID- 25394094
TI  - Potential implications of CYP3A4, CYP3A5 and MDR-1 genetic variants on the
      efficacy of Lopinavir/Ritonavir (LPV/r) monotherapy in HIV-1 patients.
AB  - INTRODUCTION: Several genetic single nucleotide polymorphisms (SNPs) in
      biotransformation enzymes (CYP3A4, CYP3A5) or transporter proteins (multidrug
      resistance MDR1 gene product, P-gp) are involved in PI metabolism so that PI
      pharmacokinetics is characterized by a large inter-individual variability. The
      aim of this study was: (i) to develop an in-house PCR/direct sequencing, based on
      DNA purification of full-length CYP3A4 and CYP3A5 genes (SNPs) and MDR1 C3435T
      variant; (ii) to investigate association of CYP3A4 and CYP3A5 reported or
      unreported genetic polymorphisms and MDR1-C3435T (CC homozygote, CT heterozygote,
      TT homozygote) with clinical outcome of HIV-1 infected subjects treated with PI.
      METHODS: Overall, 39 HIV-1 infected patients receiving boosted Lopinavir (LPV/r)
      monotherapy after virological suppression were genotyped and analyzed through PCR
      and direct sequencing of full-length CYP3A4 and CYP3A5 gene sequences (1) and
      MDR1 gene (C3435T). CD4+T-cell counts and plasma viral load were analyzed before
      and after LPV/r initiation; LPV/r therapeutic drug monitoring (TDM) was
      determined at 12-hours. RESULTS: LPV/r TDM (ng/ml) did not show significant
      differences among CYP3A4 or CYP3A5 SNPs, although a mean lower level of LPV/r was
      associated with detection of several SNPs: CYP3A5*3 rs776746; CYP3A5 rs28365088,
      CYP3A5 rs15524, CYP3A4 rs2687116, and a not already described polymorphism CYP3A4
      nt20338. In follow-up analysis, <90% adherence was the main factor associated
      with virological failure of LPV/r monotherapy (83.3% of failure vs 34.4%, p<0.001
      at log-rank test). Adjusting for adherence, the detection of a single CYP3A5*3
      rs776746 and CYP3A5 rs15524 SNPs was associated with higher probability of LPV/r
      monotherapy failure (p<0.01), and in general, detection of any CYP3A5 SNP was
      associated with failure (26.2% vs 58.3%, p=0.067). No-association with detection
      of any CYP3A4 SNPs was found. MDR1 TT variants showed significant lower frequency
      of treatment failure (0.0% vs 47.7%, p=0.026), since non-TT homozygote patient
      failed LPV/r monotherapy. CONCLUSIONS: Efficacy of PI monotherapy is strongly
      dependent from patient adherence, but, in adherent patients, genetic factors,
      such as CYP3A5 and MDR1-C3435T gene variants, may affect the response to
      treatment, though their role, as well of other genetic variants, need further
      investigation.

PMID- 25394095
TI  - Efficacy, safety, and lack of interactions with the use of raltegravir in HIV
      infected patients undergoing antineoplastic chemotherapy.
AB  - INTRODUCTION: Concomitant use of combination antiretroviral regimen (cART) and
      cancer chemotherapy is difficult due to complex interactions and increased
      toxicity. Raltegravir could be an adequate option through its favourable drug
      drug interaction profile. METHODS: Prospective longitudinal study of HIV patients
      with cancer, AIDS related or not, undergoing chemotherapy. Patients without
      resistance or previous failure were switched or initiated raltegravir plus two
      nucleoside analogues. Plasma trough levels of raltegravir were measured. RESULTS:
      Overall, 28 patients receiving a raltegravir-based regimen (4 naive) with
      tenofovir-emtricitabine (18 cases) or abacavir-lamivudine (10 cases) were
      included. Mean age was 46.2 years (IQR, 39-52.7), and 79% were male. Median time
      of HIV was 201.7 months, CD4+ nadir was 268 cells/mm(3), and 75% had previous
      AIDS. At the diagnosis of neoplasia, 17 were on protease inhibitors and 4 with
      efavirenz. Ten patients had a non-HIV-related cancer (three breast, two
      pancreatic, one Ewing sarcoma, one myeloblastic leukemia, one melanoma, one
      parotid adenocarcinoma, one lung), and 18 had an HIV-related cancer (nine non
      Hodgkin lymphoma, seven Hodgkin disease, two anal). Overall, 43% of patients
      received more than one line of chemotherapy, including antimetabolites in 12
      patients (5-FU, capecitabine, methotrexate, gemcitabine), alkylating agents in 12
      cases (ciclophosphamide, iphosphamide), vinca alkaloids in 20 patients
      (vincristine, vinblastine, vindesine), antitumor antibiotics in 16 cases
      (adriamycin), cisplatin o carboplatin in six and monoclonal antibodies in six
      patients (rituximab, trastuzumab, cetuximab). Six patients modified the doses of
      antineoplastic agents due to toxicity (four neutropenia), not related to
      raltegravir. During a median follow up of 12.7 patients-year in concomitant
      therapy, there was only 1 case of virological failure and no patient discontinued
      raltegravir. Plasma concentrations of raltegravir in eight patients showed a
      median concentration of 143 ng/mL (79-455). Four patients (14%) died during the
      study, not related to AIDS progression. Raltegravir was continued after
      chemotherapy in all the cases. CONCLUSIONS: A raltegravir-based therapy is safe
      and effective in HIV patients undergoing antineoplastic chemotherapy, regardless
      of the type of tumour, and type and duration of chemotherapy. Pharmacokinetic
      data show adequate raltegravir levels.

PMID- 25394096
TI  - Should we offer routine hepatitis C antibody testing in men who have sex with
      men?
AB  - INTRODUCTION: There has been a significant rise in the number of HIV positive men
      who have sex with men (MSM) co-infected with hepatitis C (HCV). Most infections
      are thought to occur through high risk sexual practices, exacerbated by drug use.
      Previous data has suggested no need for routine screening in HIV negative MSM. We
      looked at HCV antibody testing and HCV risk assessment in all MSM clinic
      attenders as part of a Public Health England initiative. MATERIALS AND METHODS:
      Routine HCV antibody testing was offered to all MSM attending a large inner city
      sexual health clinic from April to June 2014. Patients were asked to fill in a
      questionnaire assessing HCV risk. Demographic data, HIV status and STI results
      were collected and compared. RESULTS: We collected 471 HCV risk assessment
      questionnaires during the eight-week period. The median age was 34 (range 18-71)
      and 403 (85.6%) were White British. Ten (2.1%) patients were known to be HCV
      positive, of which 3 were on treatment and 5 (1.1%) had cleared HCV. One hundred
      and forty-nine (31.6%) patients were HIV negative, 254 (53.9%) were HIV positive
      and 68 (14.5%) had unknown HIV status at time of clinic visit. In the last three
      months 151 (32.1%) reported unprotected receptive anal intercourse, 58 (12.3%)
      reported group sex, 11 (2.3%) reported receptive fisting and 32 (6.8%) reported
      more than 10 partners. Eighty-seven (18.5%) patients had shared notes/straws to
      snort drugs and 29 (6.2%) reported injecting drugs or slamming. One hundred and
      forty-two (30.0%) patients reported recreational drug use in the last 12 months,
      with cocaine, methadrone and ketamine most popular. One hundred and fifteen
      (24.4%) patients reported sex under the influence of recreational drugs. There
      were no statistical differences between HIV positive and HIV negative patients in
      their risk, sexual behaviour and drug use. STI screens were performed on 269
      patients with nine (3.3%) new HIV diagnoses, four (1.5%) early syphilis, and 28
      (10.4%) rectal gonorrhoea infections. There were three (1.1%) new HCV diagnoses,
      and one (33.3%) was in an HIV negative patient. CONCLUSIONS: Our results show
      increased risk behaviour for both HIV positive and HIV negative MSM. There are a
      high number of patients using party drugs, participating in group sex and not
      using condoms, leading to high rates of new STI diagnoses. With similar rates of
      risk we believe HCV testing and risk assessment should be considered in all MSM
      regardless of HIV status.

PMID- 25394097
TI  - HIV positive asylum seekers receiving the order to leave the Belgian territory.
AB  - INTRODUCTION: In a human rights based approach, the Parliamentary Assembly of the
      Council of Europe has recently released a resolution about migrants and refugees
      and the fight against HIV (1). It states that "an HIV positive migrant should
      never be expelled when it is clear that he will not receive adequate health care
      and assistance in the country to which he is being sent back. To do otherwise
      would amount to a death sentence for that person." Nevertheless, in Belgium, for
      the last 2 years, none of the HIV-infected migrants in care in the AIDS Reference
      Centers (ARC) received the right to stay in Belgium for medical reasons. METHODS:
      We identified all HIV-infected asylum seekers in care between 1 July 2012 and 1
      July 2014 in the ARC of Charleroi, Belgium, and we analyzed their medical and
      social files. RESULTS: Among the 302 patients in active follow up in our ARC, 45
      HIV positive asylum seekers were in care during the last 2 years. Male/female
      ratio was 0/96. Mean age was 35 years. Countries of origin and reasons for
      migration are detailed in the Table 1. 18% (8/45) knew their seropositivity
      before arriving in Europe. All the patients introduced an asylum request, 29
      (64%) have received a negative answer and an order to leave the territory, 4 (9%)
      were regularized for non-medical reasons (see Table 1), 4 (9%) are waiting for an
      answer and for 8 (18%) outcome is unknown due to lost follow up (LFU). 31 (69%)
      patients have also introduced a request to stay for medical reasons: 18 (58%)
      have received a refusal, 7 (23%) are still waiting for an answer, and 6 (19%) are
      LFU. Only 23 (51%) patients are still in care in our ARC on 1 July 2014 (see
      Table 1). The immigration office bases its decisions on availability of the
      treatment in the country even if accessible only to a limited number of patients.
      CONCLUSIONS: Decisions taken by the Belgian authorities for the last two years
      concerning HIV-infected asylum seekers do not guarantee the continuity of care of
      those patients and push them towards illegality. Such decisions ignore the
      international commitments of Belgium in the fight against HIV (2) and are
      contradictory with the recommendations of the recent resolution of the Council of
      Europe (1). An approach more respectful of Human Rights in the decisions
      concerning the seropositive asylum seekers patients taken by the authorities is
      urgently needed in Belgium. We invite our European colleagues to describe the
      situation of the HIV asylum seekers in their countries.

PMID- 25394098
TI  - EATG training academy STEP-UP: skills training to empower patients.
AB  - INTRODUCTION: Most existing conventional capacity building and educational
      programs are currently executed on ad-hoc basis. Such approach no longer responds
      to the needs and capabilities of patients, supporters and healthcare providers in
      their engagement with and contribution to response to HIV/AIDS. In contrast, long
      term, course-like trainings have considerably broader thematic scope and are
      conducive to more effective and sustainable learning, exchange of experience and
      best practices. METHOD: Over the period of one year, the Academy trains a cohort
      of 20 activists (10 from East Europe and Central Asia and 10 from Western and
      Southern Europe). The Academy goes beyond "treatment only" paradigm.
      Conceptually, five training modules are grouped under three larger domains:
      treatment literacy, treatment advocacy and treatment activism, thus covering most
      of the topics pertinent to the current discourse of HIV and related co
      infections. To ensure cascade effect and sustainability of the learning, the
      trainees are offered participation in pan-European HIV conferences (EACS and HIV
      Glasgow) and resources for follow-up activities. RESULTS: The trainees
      empirically applied the knowledge to the benefits of their communities. In
      Uzbekistan, a trainee introduced EACS treatment guidelines to fellow medical
      students and junior doctors. In Armenia and Albania a series of small-scale
      trainings were held, outreaching to young homeless people who were traditionally
      excluded from HIV treatment and prevention discourse in the two countries. A
      trainee from Spain used the materials of the Academy in his work in Mozambique
      and the Spanish Ministry of Health. Five trainees engaged in a joint European
      cross-countries project on treatment literacy for young people who are most at
      risk of infection. CONCLUSIONS: EATG Training Academy is a unique initiative in
      the WHO Europe region that both trains future treatment activists and addresses
      treatment literacy, advocacy and advocacy topics. This type of capacity building
      can respond to existing HIV-related problems more effectively using less limited
      resources and reaching out to larger communities.

PMID- 25394099
TI  - Using social network methods to reach out-of-care or ART-nonadherent HIV+
      injection drug users in Russia: addressing a gap in the treatment cascade.
AB  - INTRODUCTION: HIV treatment to reduce downstream HIV incidence and to decrease
      disease mortality and morbidity at a population level both require that hidden,
      out-of-care people living with HIV (PLH) in the community be reached and engaged
      to enter care. This research evaluated the feasibility of reaching out-of-care or
      non-adherent PLH through members of their social networks in St Petersburg,
      Russia. MATERIALS AND METHODS: To recruit a social network sample of HIV-positive
      injection drug users, 16 HIV+ seeds were enrolled into the study through PLH
      oriented websites and online forums using recruitment ads or approached in needle
      exchange sites. Interested persons called the study phone number and completed a
      brief eligibility interview. Seed inclusion criteria were HIV+ status, being 18
      years or older, having ever injected drugs, and having not visited an HIV doctor
      in the past 6 months. Seeds provided blood specimens tested for HIV to confirm
      their self-reported status. Eligible seeds were enrolled, completed brief network
      elicitation interview, and were asked to invite their own HIV+ friends into the
      study. Incentives were provided as compensation for participants' time and
      additional smaller incentives were provided for inviting each HIV+ network member
      to also participate. The seed's PLH friends established the first ring of
      participants who, in turn were asked to invite their own PLH friends (second
      ring). All study participants completed assessment of psychosocial wellbeing and
      sexual and injection-related HIV risk behaviour. Blood samples were collected
      from all participants to confirm their HIV+ status. RESULTS: Through this chain
      referral process, the initial 16 seeds led to the enrolment of a total of 66 PLH
      from the community (mean=4 per initial seed), most of whom - like the seed - were
      not presently in HIV care or were ART non-adherent. CONCLUSIONS: Implementation
      of treatment cascade goals requires complementing conventional paths of
      identifying PLH with feasible and effective community-based approaches such as
      described in this study. This research establishes that PLH are connected in
      their day-to-day social networks with other HIV+ persons and shows that social
      network methods can be employed to reach infected persons through their
      connections with other PLH. This method has the potential to expand the reach of
      medical care efforts and ART uptake.

PMID- 25394100
TI  - Transmission route and reasons for HIV testing among recently diagnosed HIV
      patients in HIV-TR cohort, 2011-2012.
AB  - INTRODUCTION: Routes of transmission and reasons for HIV testing are important
      epidemiologic data to analyze the epidemic and to tailor the response to AIDS.
      The aim of this study was to analyze reasons for testing and transmission ways of
      HIV among recently diagnosed HIV patients registered in the multicenter HIV-TR
      cohort in Turkey. METHODS: Transmission ways and reasons for testing of all
      patients diagnosed in 2011 and 2012 were recorded on a web-based data collection
      system and were analyzed retrospectively. RESULTS: The study included 693
      patients (561 male, 132 female) from 24 sites. Reason for HIV testing was
      available in 640 patients (92%). The most common reason for HIV testing was
      diagnostic workout for other conditions or illness followed by patient-initiated
      testing. The reasons for testing were listed in Table 1. The most common routes
      of HIV transmission were heterosexual intercourse (62.7%) and sex among men who
      have sex with men (MSM) (22.6%). At the time of HIV diagnosis, the mean CD4
      lymphocyte cell count was 355/mm(3) (3-1433/mm(3)). Primary HIV infection was
      determined in 42/693 (6%) patients and 9/693 (% 1, 2) cases were considered
      "probable primary HIV infection." The majority of the cases presented to a clinic
      for follow-up right after the diagnosis. On the other hand 32/616 (5.2%) patients
      delayed their presentation for more than 3 months. The longest delay was 11
      months. CONCLUSIONS: The results of the database suggest that targeted testing is
      lacking in the country. The shift toward homosexual transmission during the last
      2 years emphasizes the need for targeted interventions. Patients present
      relatively late and HIV infection could only be diagnosed when immunosuppression
      related findings appeared. Patient-initiated testing,an indicator of awareness,
      was very low suggesting a need to scale-up awareness raising interventions.

PMID- 25394101
TI  - HIV infection early diagnosis experience in primary care.
AB  - INTRODUCTION: Traditional screening system focus on classic risk factors "lost" a
      substantial proportion of HIV-infected patients. Several organizations such as
      CDC or USPS Task Force favour universal screening for HIV infection for good cost
      effectiveness profile. In a previous study prevalence of HIV infection in
      patients attending our infectious diseases department was high (5.4%). OBJECTIVE:
      To determine prevalence of HIV infection in patients aged 20-55 years in primary
      care (PC). MATERIAL AND METHODS: A propsective observational study was undertaken
      between February and June 2013. We performed a screening of HIV infection type
      "Opt-out" (offering voluntary rejection) in 4 PC centers (32 Physicians) in San
      Juan-Alicante. Sample size (n=318) for a prevalence of 1% and a confidence level
      of 97% was calculated. Nevertheless, other PC physician not recruiting patients
      performed HIV testing according clinical risk factors. RESULTS: HIV testing was
      offered to 508 patients. Mean age 38.9+/-10 years (58.5% female). Overall, 430
      (83.8%) agreed to participate. Finally, 368 patients (71.7% of total) were tested
      for HIV. No patient had a positive result (100% ELISA HIV negative). However,
      following clinical practice, 3 patients were diagnosed of HIV in the same period
      by non-recruiting physicians. In 2 cases, serology was performed at the patient's
      request and in one case by constitutional syndrome. The 3 patients were MSM.
      CONCLUSIONS: 1) In our study, we detected no new cases of HIV infection through
      universal screening. 2) Our screened population could be lower-risk because of
      high percentage of women included (58.5%). 3) Performing HIV opt-in screening
      (clinical practice), we detected 3 cases in the same period, all having HIV risk
      factors (MSM). 4) These results suggest that opt-out screening should be
      developed in high-risk populations. It is still to be determined what is the best
      screening strategy in low-risk populations such as ours.

PMID- 25394102
TI  - HIV test: which is your best? A National survey on testing preferences among MSM
      in Italy.
AB  - INTRODUCTION: HIV testing opportunities in Italy are frequently limited to the
      hospital setting. Experiences in other countries show that offering HIV testing
      in other facilities could improve HIV testing uptake. METHODS: An internet-based
      survey was conducted between March 10 and April 3, 2014. RESULTS: A total number
      of 348 questionnaires were collected. Responders were 88% male. Most represented
      age groups were 25-34 (35%) and 35-44 (25%). Most of the responders identify
      themselves as homosexual (81%) or bisexual (9%). Half of responders had an HIV
      test within 2 years (56%) while 18% never tested for HIV. Among all responders,
      61% had more than 2 sexual partners in the past year. Reported condom use in the
      past year was: always 39%, always but once 11%, sometimes 27%, never 14%. Most
      known places to have an HIV test is the hospital (95%), STI clinic (58%) and
      chemical analysis laboratory (54%); most used places are hospital (73%), STI
      clinic (30%), laboratory (22%) while 5 responders reported having had a self-test
      at home. Preferred places where to have an HIV test is self-testing at home
      (53%), hospital (36%), pharmacy (32%) and headquarter of an organization (31%).
      Most known testing method is draw blood from vein (97%), which is also most used
      (80%) but the least preferred (31%) while saliva (65%) and finger prick (56%) are
      the preferred choices. Most responders know that physicians (84%) and nurses
      (77%) are those who perform HIV tests and most of them had an HIV test with them
      (60% and 65% respectively). Physicians are the preferred operators (54%) followed
      by self-testing (46%), nurses (46%) and peer-volunteers (39%). The ideal HIV test
      should be: reliable (86%), with no medical prescription (75%), free (63%), rapid
      (55%), with no personal information collected (45%), with the opportunity to
      speak with a peer-counsellor (36%). CONCLUSIONS: Changing HIV testing policies in
      Italy is urgently needed in order to grant a better access to the service:
      waiting for the results and bureaucratic obligations represent the major barriers
      to be removed. Home-testing and community-based testing seem to be among the best
      ways to offer new opportunities though they may require a change in the legal,
      social and cultural context to be implemented and home testing will not allow any
      kind of support for newly diagnosed people.

PMID- 25394103
TI  - Health literacy, source of information and impact on adherence to therapy in
      people living with HIV.
AB  - INTRODUCTION: Adequate information and health literacy (HL) has a high impact on
      patients understanding on the causes and consequences of many chronic diseases,
      including HIV, and is a crucial prerequisite to ensure adherence to therapy
      regimens. Several Austrian patient organizations developed an online survey
      together with MSD (the so-called "PAB-test") aimed to evaluate how people living
      with HIV perceive the level of care in Austria. MATERIALS AND METHODS: An online
      survey has been developed to assess HL in people living with HIV and to evaluate
      the impact of HL on therapy adherence. HL was assessed with seven items regarding
      the self-rated comprehension of HIV related information, which showed a high
      reliability (Cronbach's alpha=0.876). A low health literacy was defined by
      reaching a score below the median of 20 points in the related indicator. RESULTS:
      A total of 303 subjects completed the questionnaire. Women slightly had more
      often a low HL than men (57.1% vs 44.7%, p=0.335). Heterosexual subjects had more
      often a low HL compared to homosexual ones (58.3% vs 38.1%, p=0.007). Health
      literacy slightly increased with age (not significant). An increasing education
      level correlated with higher HL, (66.7%, 46.2%, and 38.9% of persons showed low
      HL with primary, secondary and tertiary education, respectively, p=0.037). The
      number of missed appointments with the HIV physician was significantly higher in
      the low HL population (30.0% vs 14.4%, p=0.002), which also showed to be more
      prone to interrupt the therapy without consulting a physician (22.4% vs 9.8%,
      p=0.006). The low HL population, however, did not report of having forgotten the
      medication intake more often than the one with high HL (33.1% vs 39.1%, p=0.305).
      The most important source of information is the treating physician, followed by
      NGOs/patient organizations and the internet (Figure 1). CONCLUSIONS: There are
      significant differences in HL between different sub-groups in the HIV community.
      Low HL is significantly associated with a higher frequency of missed doctor
      appointments and interruptions of treatment, but does not impact adherence to
      therapy (self-reported). The identified information providers (medical doctors,
      NGOs/patient organizations) should be encouraged to contribute towards increased
      HL in HIV patients.

PMID- 25394104
TI  - Involvement of HIV patients in treatment-related decisions.
AB  - INTRODUCTION: The improvement of antiretroviral therapy in the past decades has
      had a major impact on life expectancy and quality of life of people living with
      HIV, and also on the relationship between patients and their physicians. What
      used to be an acute treatment for life threatening complications, and an end-of
      life therapy in the beginning of the epidemic, turned over the time into a
      lifelong care. The good relationship between patients and physicians represents
      the cornerstone of an optimal long-term therapy. Shared decision making between
      patients and physicians is a crucial prerequisite for the success of this
      approach. Several Austrian patient organizations developed an online survey
      together with MSD (the so-called "PAB-test") aimed to evaluate how people living
      with HIV perceive the level of care in Austria. MATERIALS AND METHODS: An online
      survey has been developed to evaluate how people living with HIV feel about the
      relationship with their physicians and to what extent they feel involved in
      treatment related decisions. RESULTS: A total of 303 subjects completed the
      questionnaire. 44% felt "totally" involved in their therapy, 40% "strongly
      involved", 12% "fairly involved", 3% "poorly involved" and 1% "not at all
      involved" in their therapy. The proportion of subjects who felt totally involved
      in the therapy was equally distributed between sex, sexual orientation, age
      groups, groups of various education level, and between patients treated
      predominantly in intramural or extramural medical care. The most important factor
      for people living with HIV to feel involved in their therapy is a low amount of
      long-term ART-related side-effects (Figure 1). CONCLUSIONS: The results show that
      the majority of people living with HIV in Austria feel involved in therapy
      related decisions. This proportion is equally distributed in patients with
      different socio-demographic or socio-economic characteristics or level of medical
      care delivery. According to the survey, the most important reason for people
      living with HIV to be involved in their therapy is to avoid long-term side
      effects.

PMID- 25394105
TI  - Improve screening of HCV infection by targeting high prevalence aged groups:
      analysis of a cohort of HCV and HIV co-infected patients.
AB  - INTRODUCTION: Hepatitis C constitutes a major public health burden. In Portugal,
      the prevalence is estimated at 1-1.5% (1). Of these, only 30% are presumed to be
      diagnosed, which reveals that most infections go unknown. The objective of this
      study is to identify the age-range distribution at HCV diagnosis and to identify
      the high-prevalence birth groups that could be targeted for screening, as a
      strategy to increase diagnosis and identify patients who would benefit most from
      treatment. METHODS: Retrospective observational study of a cohort of chronic HCV
      infected and HIV co-infected patients followed at an Infectious Diseases Center,
      diagnosed between 1979 and 2014 (Figure 1). Hepatic fibrosis evaluation was
      performed by real time elastography using METAVIR score. Epidemiological,
      demographic, clinical, virological and therapeutic data was retrieved from
      clinical registries. Statistical analysis was performed using Microsoft Excel
      2010(r). Chi2, Student T were used for a significant p value of <0.05. RESULTS:
      Our study assessed a cohort of 665 patients: 442 (66.5%) HCV/HIV co-infected and
      223 (33.5%) HCV monoinfected. There was a male predominance in both groups (74.9%
      vs 70.9%). The mean age was 47 HCV/HIV vs 49 years; Portuguese origin in 80% vs
      83% and African in 14% vs 12%. The most frequently assumed transmission route was
      by intravenous drug use (IVDU) (81% vs 72%), followed by sexual contact (18% vs
      20%). Mean age at diagnosis was 32 vs 40 years. Mean time since HCV diagnosis was
      14, 6 vs 9, 6 years. Fibrosis stage evaluation by real time elastography was
      available for 133 (30%) and 99 (44.4%) patients (HCV/HIV vs HCV): 16% vs 13% F1;
      32% vs 33% F2; 31% vs 35% F3; 21% vs 18% F4. The peak prevalence occurred between
      the birth intervals of 1960-1969 and 1970-1979 for both groups, corresponding to
      81% vs 66,8% (p=0.003) (Figure 1). About three quarters of all patients (76%)
      were born between the year of 1960 and 1979, with a prevalence of 70% of IVDU.
      CONCLUSIONS: In our cohort we identify a high risk population for chronically HCV
      infection, which comprises people born between 1960 and 1979, findings common to
      those with mono or HIV co-infection. This finding is concordant with the epidemic
      of IVDU in Portugal around 1980-1990. These patients should be screened for
      diagnosis in order to be treated and to prevent further disease progression.

PMID- 25394106
TI  - Future prospectives of sub-Saharan women living with HIV residing in France for
      more than seven years: prospective pilot study.
AB  - INTRODUCTION: In 2011, a French national survey of people living with HIV (PLHIV)
      has shown that 40% of persons diagnosed since 2003 are originated from sub
      Saharan Africa, two thirds of them being women. For them, in the short term,
      access to social rights is a priority. Today, over 90% of PLHIV are treated
      effectively and with the aging of this population, questions about their future
      perspectives arise. Our service provides a multidisciplinary (medical,
      psychological, social) approach to PLHIV. The aim of our study is to describe the
      future perspectives of sub-Saharan women living with HIV residing in France for
      more than 7 years, because it is the time required for the implementation of
      fundamental rights and social insertion. Do they plan to return to their country
      of origin after their retirement? Does the HIV infection force them to stay in
      France? MATERIALS AND METHODS: Prospective pilot mono-centric study. Between
      January and April 2014, every HIV-infected woman born in a sub-Saharan country,
      resident in France for at least 7 years, attending for their routine outpatient
      visit was consecutively included. Data were collected through a structured, semi
      directed interview made by their usual hospital physician or social worker.
      RESULTS: Consecutively, 76 women agreed to participate to the interview, none
      refused. Mean age: 42 years [26-70], time since HIV diagnosis: 12 years [1-25].
      HIV diagnosis was made before arriving in France for 3% of them; in 33% diagnosis
      was made in the year of arrival; diagnosis made several years after arrival in
      63%. Even if 69% of these women had been irregularly residing in France for a
      period, all of them had obtained a regular situation for residence and 50%
      acquired the French nationality. Mean duration of residence was 15 years [7-33].
      Two thirds of them are employed. In the future, although 50% plan to have a
      shared residence between France and Africa, only 20% of them plan to settle back
      definitely in Africa and no woman declared that she would look for a medical
      follow up in Africa for their HIV infection. CONCLUSIONS: This study shows a good
      integration in France of HIV-infected sub-Saharan woman. Their links with Africa
      remain strong but very few plan to return in their country of origin due to lack
      of confidence in the African health infrastructures.

PMID- 25394107
TI  - Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the
      dual therapy with LPV/r+3TC for initial ART in HIV infected adults.
AB  - INTRODUCTION: The National AIDS Plan and the Spanish AIDS study group (GESIDA)
      panel of experts propose "preferred regimens" of antiretroviral treatment (ART)
      as initial therapy in HIV-infected patients for 2013 [1]. All these regimens are
      triple therapy regimens. The Gardel Study assessed the efficacy and safety of a
      dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) 400/100 mg BID+
      lamivudine (3TC) 150 mg BID [2]. The objective of this study is to evaluate the
      costs and efficiency of initiating treatment with the GESIDA "preferred regimens"
      and DT. MATERIALS AND METHODS: Economic assessment of costs and efficiency
      (cost/efficacy) through decision tree analysis models. Efficacy was defined as
      the probability of having viral load <50 copies/mL at week 48, in an intention-to
      treat analysis. Cost of initiating treatment with an ART regime was defined as
      the costs of ART and its consequences (adverse effects, changes of ART regime and
      drug resistance tests) during the first 48 weeks. The payer perspective (Spanish
      National Health System) was applied considering only differential direct costs:
      ART (official prizes), management of adverse effects, resistance tests, and
      determination of HLA B*5701. The setting is Spain and the costs are those of
      2013. A sensitivity deterministic analysis was conducted, building three
      scenarios for each regime: base, most favourable and most unfavourable cases.
      RESULTS: In the base case scenario, the cost of initiating treatment ranges from
      5138 euros for DT, to 12,059 euros for tenofovir DF/emtricitabine
      (TDF/FTC)+raltegravir (RAL). The efficacy ranges between 0.66 for abacavir
      (ABC)/3TC+LPV/r and ABC/3TC+atazanavir (ATV)/r, and 0.88 for DT. Efficiency, in
      terms of cost/efficacy, varies between 5817 and 13,930 euros per responder at 48
      weeks, for DT and TDF/FTC+RAL respectively. DT is the most efficient regimen in
      the most favourable (5503 euros per responder) and most unfavourable (6169 euros
      per responder) scenarios. CONCLUSIONS: Considering the ART official Spanish
      prizes, the most efficient regimen was DT, followed by the triple therapy with
      non-nucleoside containing regimens. The sensitivity analysis confirms the
      robustness of these findings.

PMID- 25394108
TI  - Prices of second-line antiretroviral treatment for middle-income countries inside
      versus outside sub-Saharan Africa.
AB  - INTRODUCTION: Antiretrovirals are available at low prices in sub-Saharan Africa,
      but these prices may not be consistently available for middle-income countries in
      other regions with large HIV epidemics. Over 30% of HIV infected people live in
      countries outside sub-Saharan Africa. Several key antiretrovirals are still on
      patent, with generic production restricted. We assessed price variations for key
      antiretroviral drugs inside versus outside sub-Saharan Africa. METHODS: HIV drug
      prices used in national programmes (2010-2014) were extracted from the WHO Global
      Price Reporting Mechanism database for all reporting middle-income countries as
      classified by the World Bank. Treatment costs (branded and generic) were compared
      for countries inside sub-Saharan Africa versus those outside. Five key second
      line antiretrovirals were analysed: abacavir, atazanavir, darunavir,
      lopinavir/ritonavir, raltegravir. RESULTS: Prices of branded antiretrovirals were
      significantly higher outside sub-Saharan Africa (p<0.001, adjusted for year of
      purchase) (see Table 1). For example, the median (interquartile range) price of
      darunavir from Janssen was $732 (IQR $732-806) per person-year in sub-Saharan
      Africa versus $4689 (IQR $4075-5717) in non-African middle-income countries, an
      increase of 541%. However, when supplied by generic companies, most
      antiretrovirals were similarly priced between countries in sub-Saharan Africa and
      other regions. CONCLUSIONS: Pharmaceutical companies are selling antiretrovirals
      to non-African middle-income countries at prices 74-541% higher than African
      countries with similar gross national incomes. However, generic companies are
      selling most of these drugs at similar prices across regions. Mechanisms to
      ensure fair pricing for patented antiretrovirals across both African and non
      African middle-income countries need to be improved, to ensure sustainable
      treatment access.

PMID- 25394109
TI  - Cost-effectiveness of DTG+ABC/3TC versus EFV/TDF/FTC for first-line treatment of
      HIV-1 in the United States.
AB  - INTRODUCTION: Data from the SINGLE trial demonstrated that 88% of treatment-naive
      HIV-1 patients treated with dolutegravir and abacavir/lamivudine (DTG+ABC/3TC)
      achieved viral suppression at 48 weeks compared with 81% of patients treated with
      efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC). It is
      unclear how this difference in short-term efficacy impacts long-term cost
      effectiveness of these regimens. This study sought to evaluate the long-term cost
      effectiveness of DTG+ABC/3TC versus EFV/TDF/FTC from a US payer perspective.
      MATERIALS AND METHODS: An individual discrete-event simulation model tracked the
      disease status and treatment pathway of HIV-1 patients. The model simulated
      treatment over a lifetime horizon by tracking change in patients' CD4 count,
      occurrence of clinical events (opportunistic infections, cancer and
      cardiovascular events), treatment switch and death. The model included up to four
      lines of treatment. Baseline patient characteristics, efficacy and safety of
      DTG+ABC/3TC and EFV/TDF/FTC were informed by data from the SINGLE trial. The
      efficacy of subsequent lines of treatment, clinical event risks, mortality, cost
      and utility inputs were based on literature and expert opinion. Outcomes were
      lifetime medical costs, quality-adjusted life-years (QALYs) (both discounted at
      3% per annum) and the incremental cost-effectiveness ratio (ICER). RESULTS:
      Compared with EFV/TDF/FTC, DTG+ABC/3TC increased lifetime costs by $58,188 and
      per-person survival by 0.12 QALYs, resulting in an ICER of $482,717/QALY. In
      sensitivity analyses testing conservative assumptions about EFV/TDF/FTC's
      efficacy beyond the trial period, ICERs comparing DTG+ABC/3TC to EFV/TDF/FTC
      remained high (lowest reported ICER of $365,662/QALY). In a scenario in which the
      price of EFV/TDF/FTC was reduced by 10% to reflect the potential for price
      reduction as EFV goes off patent, DTG+ABC/3TC's ICER compared to EFV/TDF/FTC was
      $600,916/QALY. When DTG+ABC/3TC's price was reduced by 10%, the resulting ICER
      comparing DTG+ABC/3TC to EFV/TDF/FTC was $302,171/QALY. CONCLUSIONS: Compared
      with EFV/TDF/FTC, DTG+ABC/3TC resulted in substantially higher cost, slightly
      better QALY over lifetime, and ICERs far exceeding standard cost-effectiveness
      thresholds, indicating that the incremental benefit in efficacy associated with
      DTG+ABC/3TC may not be worth the incremental increase in costs.

PMID- 25394110
TI  - Incremental cost per newly diagnosed HIV infection (NDHI): routine (RTS),
      targeted (TTS), and current clinical practice testing strategies (CPTS).
AB  - INTRODUCTION: Although RTS as HIV Diagnosis was considered cost effectiveness
      [1], overall budget may be unaffordable for some countries. We explore
      Incremental cost per NDHI associated with different TS. MATERIALS AND METHODS:
      From a health care perspective, using direct costs and Euros currency, we
      calculated budget and cost per NDHI of RTS (all patients were tested), TTS
      (Universal risk practices and clinical conditions-RP&CC - only positive were
      tested), and CPTS (Only patients physicians considered were tested). We
      considered DRIVE (Spanish acronym of HIV infection Rapid Diagnosis) study and
      clinical Practice outcomes. Population between 18-60 years, attending to a
      Hospital Emergency Room or to a Primary Care Center performed an HIV RP&CC
      questionnaire (Q) and an HIV rapid test (HIV RT). Unitary costs considered were:
      HIV RT, nurse, registry, transport and HIV confirmation when necessary, imputed
      to all population in RTS and CPTS and only in HIV RP&CC-Q positive in TTS
      analysis, while HIV RP&CC-Q costs were added to all population in TTS.
      Sensitivity analyses were performed with varying rates of NDHI and of positive
      HIV RP&CC-Q population, and different RP&CC Q sensitivity (SE) to predict HIV
      infection. RESULTS: 5,329 HIV RP&CC-Q and HIV RT were performed to 49.64% women,
      median age 37 years old, 74.9% Spaniards. In DRIVE and CP, NDHI were 4.10/00, and
      1.60/00, while HIV RP&CC-Q was positive in 51.2%. HIV RP&CC-Q SE was 100%.
      Overall budget employed in HIV testing was in RTS 43,503?, in TTS 24,472? and in
      CPTS 5,032?. Cost per 1 NDHI was 1,977?, 1,112? and 5,032?, respectively. A
      reduction in cost of 865?, favouring TTS vs. RTS, while an increased cost of 824?
      in CPTS vs. RTS was obtained. Considering NDHI rate of 2.60/00 saving costs
      increased to 1379? in TTS, while were reduced to 576? if NDHI rate increases
      6.20/00. Effect of RP&CC-Q positivity rate was similar, if 25% saving costs were
      1368?, while if 75% were reduced to 399?. Varying SE of RP&CC-Q to 95%, 91% and
      50% cost saving was 810?, 754?, and 208?, and number of MHI one, two and 11.
      CONCLUSIONS: In DRIVE study Targeted TS with universal screening of RP&CC before
      an HIV rapid test is cost saving, without missing NDHI, with respect to Routine
      TS. Lower rates of HIV infection and RP&CC in the population, increase costs
      savings.

PMID- 25394111
TI  - Reducing turnaround time for laboratory test results does not improve retention
      of stable HIV-infected adults on POV program: experience from Uganda.
AB  - INTRODUCTION: HIV/ AIDS clinics in resource limited settings (RLS) face
      increasing numbers of patients and workforce shortage [1, 2]. To address these
      challenges, efficient models of care like pharmacy only visits (POV) and nurse
      only visits (NOV) are recommended [3]. The Makerere University Joint AIDS Program
      (MJAP), a PEPFAR funded program providing care to over 42,000 HIV infected adults
      has implemented the POV model since 2009. In this model, stable patients on
      antiretroviral therapy (ART) with adherence to ART >95% and Karnofsky score >90%
      are reviewed by a doctor every four months but visit pharmacy for ART re-fills
      every two months. A study conducted in August 2011 showed low retention on the
      POV program with symptomatic diseases, pending CD4 count, complete blood count
      results, and poor adherence to ART as the major reasons for the non-retention in
      the POV program. To improve retention on POV, the TAT (Turnaround Time) for
      laboratory results (the main reason for non-retention in the previous study) was
      reduced from one month to one week. In August 2012, the study was repeated to
      assess the effect of reducing TAT on improving retention one year after patients
      were placed on POV. MATERIALS AND METHODS: A cohort analysis of data from
      patients in August 2011 and in August 2012 on POV was done. We compared retention
      of POV before and after reducing the TAT for laboratory results. RESULTS:
      Retention on POV was 12.0% (95% CI 9.50-14.7) among 619 patients in 2011, (70%
      Females), mean age was 33 years, Standard Deviation (SD) 8.5 compared to 11.1%
      (95% CI 9.15-13.4) among 888 patients (70% Females), mean age 38.3 years, SD 8.9
      in 2012 (p=0.59). The main reasons for non-retention on the POV program in 2012
      were poor adherence to ART (23%) and missed clinic appointments (14%).
      CONCLUSIONS: Reducing TAT for laboratory test results did not improve retention
      of stable HIV-infected adults on POV in our clinic. Strategies for improving
      adherence to ART and keeping clinic appointments need to be employed to balance
      workload and management of patients without compromising quality of care,
      patients' clinical, immunological and adherence outcome.

PMID- 25394112
TI  - Acceptability and confidence in antiretroviral generics of physicians and HIV
      infected patients in France.
AB  - INTRODUCTION: Switching brand name medications to generics is recommended in
      France in the interest of cost effectiveness but patients and physicians are
      sometimes not convinced that switching is appropriate. Some antiretroviral (ARV)
      generics (ZDV, 3TC, NVP) have been marketed in France since 2013. MATERIALS AND
      METHODS: A multicentric cross-sectional survey was performed in September 2013 to
      evaluate the perception of generics overall and ARV generics in physicians and
      HIV-infected patients and factors associated to their acceptability. Adult HIV
      outpatients were asked to complete a self-questionnaire on their perception of
      generics. Physicians completed a questionnaire on the acceptability of generics
      and ARV generics. Socio-demographic data, medical history and HIV history were
      collected. RESULTS: 116 physicians in 33 clinics (68% in University Hospital)
      included 556 patients (France-native 77%, active employment 59%, covered by
      social Insurance 100%, homosexual/bisexual contamination 47%, median HIV duration
      13 years, hepatitis coinfection 16%, on ARV therapy 95%). Overall, patients
      accepted and had confidence in generics in 76% and 55% of the cases,
      respectively. Switching ARVs for generics was accepted by 44% of the patients but
      only by 17% if the pill burden was going to increase. 75% of the physicians would
      prescribe generics, but this decreased to only 26% if the combo had to be broken.
      The main reasons for non-prescription of generics were previous brand name ARV
      induced side effects (35%), refusal of generics overall (37%), lack of
      understanding of generics (26%), risk of non-observance of treatment (44%),
      anxiety (47%) and depressive symptoms (25%). In multivariate analysis, factors
      associated with the acceptability of ARV generics in patients were the use of
      generics overall (p<0.001) and in physicians, the absence of concern regarding
      the drug efficacy (p<0.001) and being aware that the patient would accept
      generics overall (p=0.03) and ARV generics (p=0.04). No factors related to
      sociodemographic conditions, HIV status or comorbidities had a constrictive
      influence on the use of ARV generics. CONCLUSION: Acceptability of ARV generics
      in this French population is mostly dictated by the patient's and physician's
      knowledge and use of generics overall. Switching ARV brand name to a generic
      would be better accepted if the pill burden remained unchanged.

PMID- 25394113
TI  - Hidden costs of HIV treatment in Spain: inefficiency of the antiretroviral drug
      packaging.
AB  - INTRODUCTION: Antiretroviral drugs in Spain are delivered by law only in hospital
      pharmacies. Commercial packages meet variable quality standards when dispensed
      drugs are returned due to treatment changes or adherence problems Nearly 20-25%
      of the initial regimens will be changed at 48 weeks for different reasons. We
      evaluated the economic impact on public health system of the inability of using
      returned drugs due to inefficient packaging. MATERIALS AND METHODS: We defined
      socially efficient packaging as the best adapted one to being delivered in unit
      dose to outpatients and classified: Class A - Drug packed in unit doses with
      complete info (name of drug, dosage in mg, lot, and expiring date) in each unit,
      maintaining complete information of the drug if returned when the external
      package is opened. Class B - packed in blisters with complete info in the
      blister, but not in unit doses, without special conservation conditions (should
      be re-packed in unit doses in the pharmacy before its dispensation to assure a
      class A excellence). Class C - packed in plastic containers with complete info
      written only on a label over the container, would allow repackaging only before
      its initial delivery, but not when returned. Class D - drug packed in plastic
      containers with manufacturer's warning that the product cannot be placed outside
      of the original package due to special conditions of conservation (fridge,
      humidity) that doesn't allow a unit dose repackaging or reusing an opened
      container. We analysed a 12-month period (July 2011-June 2012) in a hospital
      based HIV outpatient pharmacy that serves 2413 treated individuals. RESULTS:
      Patients generated 23,574 visits to pharmacy, and received 48,325 drug packages,
      with 2.529.137 pills delivered. The patients suffered 1051 treatment changes for
      any reason. A total amount of 122.945? in treatment were returned to pharmacy in
      opened packages during the study period. 47.139.91? would be totally lost, mainly
      due to being packaged in class C and D boxes, the equivalent of treating 78
      patients with rilpivirine/TDF/FTC during 1 month. Class A and B packages in bad
      condition represented only 1.1% of the cost. However, 75.805? came from returned
      packages in good condition that could potentially be reused. Most of the
      treatment changes were not foreseeable. CONCLUSIONS: A significant economic
      budget is lost through socially inefficient antiretroviral packages. Newer
      treatments are packaged in C and D categories, therefore maintaining these hidden
      costs in the near future. Any improvement in the excellence of packaging by the
      manufacturer, and favouring the choice of drugs supplied through efficient
      packages (when efficacy, toxicity and convenience are similar) should minimize
      the treatment expenditures paid by national health budgets.

PMID- 25394114
TI  - The cost-effectiveness in the use of HIV counselling and testing-mobile
      outreaches in reaching men who have sex with men (MSM) in northern Nigeria.
AB  - INTRODUCTION: Men who have sex with men (MSM) are at increased risk of HIV and
      other STI infections in Nigeria. This is because MSM are afraid to seek medical
      help because the healthcare workers in various facilities are afraid of the
      consequences if they provide services for MSM citing the law as a reason not to
      intervene. MSM in northern states of Nigeria are facing double-jeopardy because
      the few international partners working in MSM in Nigeria are pulling out of these
      volatile areas because of the fear of attacks by the Boko Haram and the Nigerian
      law enforcement agencies. OBJECTIVES: The intervention was conducted to promote
      affordable and sustainable HIV care and treatment for MSM in Nigeria. METHODS:
      This intervention was conducted in the Boko Haram ravaged cities of Kano and
      Maiduguri (North-East Nigeria). Twenty MSM-key influencers from the two cities
      were identified and trained on HIV counselling and testing, caregivers, case
      managers and on initiation process for ARV treatment for new HIV+MSM as well as
      ethical considerations. RESULTS: The mean age of the key influencers was 24 years
      +/-SD. Each of the trained 20 key influencers reached 20 MSM-peer with condom
      promotion, HCT, referral to identified MSM-community health centers and follow
      up/caregiving within the space of one month. The project was able to reach 400
      MSM in the two cities. 89% of the peers consented to HCT. HIV prevalence among
      the participants was at 18%. The project recorded ARV-successful referral to
      healthcare facilities for the respondents that tested positive. The key
      influencers have been following up for ARV-adherence. CONCLUSIONS: Use of
      community members should be promoted for sustainability and ownership. It also
      helps in eradicating socio-cultural barrier to HIV intervention for MSM.
      Moreover, this proves to be one of the safest and affordable methods of reaching
      MSM in Nigeria in this ugly time of legalization of homophobia in the country's
      constitution.

PMID- 25394115
TI  - Determinants of HIV outpatient service utilization according to HIV parameters.
AB  - INTRODUCTION: The increased life expectancy of HIV patients in the era of highly
      active antiretroviral therapy has had profound consequences for the healthcare
      systems that provide their care. It is useful to assess whether healthcare
      resources need to be adapted to the different stages of HIV infection or to
      patient characteristics [1]. To study how patient features influence utilization
      of out patient services, we retrospectively analyzed the electronic health record
      of HIV-positive patients who had followed day-care programs at the AIDS Center of
      the University of Palermo, Italy. MATERIALS AND METHODS: 223 HIV-infected
      subjects were recruited and divided into two groups according to CD4 cell counts
      (117 with a CD4 count <=500/mm(3) and 106 with CD4 count >=500/mm(3)). Data on
      age, gender, race, lifestyle habits (including educational level, drug abuse
      history, smoking status, alcohol consumption, sexual behaviour) BMI, HIV-RNA,
      CD4+ T-cell count, antiretroviral therapy (ART), comorbidities such as HCV co
      infection, osteoporosis biomarker, dyslipidemia, diabetes, renal function and
      systolic and diastolic blood pressure were recorded in a purposely designed
      database and were analyzed in relation to AIN by uni- and multivariable logistic
      regression. RESULTS: Table 1 shows the characteristics of enrolled patients; the
      average age of the recruited patients was 45.4+/-9.5 years. 163 individuals were
      male (73%), 26 were immigrants (12%) and 91 (40%) were treatment-naive. Mean day
      care access for laboratory tests to evaluate stage of HIV and for treatment
      monitoring was 6.5 days for CD4 cell count measurements and 9.6 for HIV RNA/drug
      resistance testing. When patients were stratified according to CD4 count, mean
      day care access for laboratory tests to evaluate HIV stage and to monitor
      treatment was negatively correlated with CD4 cell counts. CONCLUSIONS: Only
      patients with CD4 counts <=500/mm(3) showed higher rates of healthcare
      utilization; these data may be useful for monitoring and revising implementation
      plans for the different phases of HIV disease.

PMID- 25394116
TI  - High rates of viral suppression in a cohort of HIV-positive adults receiving ART
      in Ethiopian health centers irrespective of concomitant tuberculosis.
AB  - INTRODUCTION: Antiretroviral therapy (ART) initiation during treatment for
      tuberculosis (TB) improves survival in HIV/TB co-infected patients. Data on ART
      outcome for HIV/TB co-infected patients managed in primary health care in low
      income regions is limited. We compared virological suppression rates, mortality
      and retention in care in HIV-positive adults receiving care in five Ethiopian
      health centres with regard to TB co-infection. MATERIALS AND METHODS: HIV
      positive ART-naive adults eligible for ART initiation were prospectively
      recruited from October 2011 until March 2013. At inclusion, all patients
      submitted sputum for microbiological TB testing (smear microscopy, liquid culture
      and PCR). Virological suppression rates after six months of ART (VS; viral load
      <40 and <400 copies/mL) with regard to TB status was the primary outcome. The
      impact of HIV/TB co-infection on VS rates was determined by multivariate
      regression analysis. Mortality and retention in care were analyzed by
      proportional hazard models. RESULTS: Among 812 participants (TB 158; non-TB 654),
      678 started ART during the follow-up period (TB 135; non-TB 543). Median CD4 cell
      counts at ART initiation were 161 cells/uL (interquartile range [IQR], 98-243)
      and 184 (IQR, 118-256) for TB and non-TB patients, respectively (p=0.05). No
      difference in retention in care between TB and non-TB patients was observed
      during follow-up; 25 (3.7%) patients died and 17 (2.5%) were lost to follow-up
      (p=0.30 and p=0.83, respectively). Overall rates of VS at six months were 72.1%
      (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects
      with and without TB co-infection (<40 copies/mL: 65/92 (70.7%) vs. 304/420
      (72.4%), p=0.74; <400 copies/mL: 77/92 (83.7%) vs. 377/420 (89.8%), p=0.10,
      respectively). CD4 cell count increase during treatment was 87 (IQR, 26-178) and
      103 cells/uL (IQR, 38-173) for TB and non-TB patients, respectively, with no
      significant difference between the two groups (p=0.49). CONCLUSIONS: High rates
      of VS were achieved in adults receiving ART at Ethiopian health centres managed
      by non-physician clinicians, with no significant difference with regard to TB co
      infection. These findings demonstrate the feasibility of combined ART and anti-TB
      treatment at primary health care level in low-income countries. This study is
      registered with clinicaltrial.gov, NCT01433796.

PMID- 25394117
TI  - Outcomes related to 4864 pregnancies with exposure to lopinavir/ritonavir
      (LPV/r).
AB  - INTRODUCTION: During pregnancy, LPV/r is a common anchor drug employed to treat
      the mother's HIV-1 infection in addition to reducing the risk of mother-to-child
      transmission (MTCT). The National Study of HIV in Pregnancy and Childhood (NSHPC)
      conducts a comprehensive population-based surveillance of HIV infection in
      pregnant women exposed to antiretroviral therapy (ART) in the UK and Ireland; in
      2003-2012 over a third of pregnancies reported to the NSHPC involved exposure to
      LPV/r. METHODS: We undertook a retrospective were descriptive analysis of
      individual NSHPC patient data, using pregnancy as the unit of observation.
      Clinical outcomes for pregnancies reported by June 2013, where women were exposed
      to LPV/r and due to deliver between January 2003 and December 2012, are
      described. RESULTS: A total of 4864 LPV/r exposed pregnancies in 4118 women were
      identified. These resulted in 4702 deliveries with 4759 live and 46 stillborn
      infants. Seventy five percent of women were born in sub-Saharan Africa, 13% in
      the UK or Ireland. Median maternal age at conception was 30 years. Nine hundred
      and eighty (20%) pregnancies were conceived while taking LPV/r, with a median
      duration of LPV/r exposure of 270 days. A total of 3884 (80%) pregnancies
      initiated LPV/r after conception, with a median duration of LPV/r exposure of 107
      days. Viral load (VL) close to delivery was available for 4083/4702 (87%)
      deliveries, with VL <50 c/mL in 73% and <1000 c/mL in 94% of women. VL by timing
      of LPV/r initiation is shown in Table 1. Sixty three percent of deliveries were
      by C-section, of which 62% were classified as elective and 38% as emergency.
      Among singleton liveborn infants, 13% were born prior to 37 weeks gestation (2.5%
      <32 weeks) and 15% had birth weight <2500 g (2.3% <1500 g). HIV infection status
      was available for 4039 (89%) singleton infants. For the periods 2003-2007 and
      2008-2012, MTCT rates were 1.1% (95% CI 0.6-1.6) and 0.5% (95% CI 0.2-0.8)
      respectively. Hundred and thirty four live born children (2.8%) had at least one
      congenital abnormality reported. CONCLUSIONS: In the NSHPC database, in women
      exposed to LPV/r during pregnancy in the UK and Ireland, MTCT rates are low and
      continue to decline, and are similar to rates in the entire NSHPC cohort of women
      with diagnosed HIV [1]. The congenital abnormality rate is comparable with that
      reported for the uninfected population in this geographic region.

PMID- 25394118
TI  - Results from a national treatment database - does it matter which ART combination
      is prescribed in the real world?
AB  - INTRODUCTION: Clinical trials frequently show differences in viral load (VL)
      response between antiretroviral therapy (ART) regimes. Patterns of prescribing
      vary from country to country (Mocroft et al. Infection 2014 Jun 6 [epub ahead of
      print]), and are likely to vary between individual clinics. Scotland has a
      national database that records VL results and specific ART regimes for every
      patient under care, thus allowing different prescribing patterns between clinical
      centres to be monitored. Does this reveal any difference in achievement of
      undetectable VL? MATERIALS AND METHODS: We interrogated the database held by
      Health Protection Scotland (HPS) that contains a record of every VL result
      matched against prescribed ART. RESULTS were censored at the end of December 2013
      and are based on the latest attendance of patients who have been under monitoring
      for at least six months. For simplicity, we have broken the results into class of
      drug rather than individual drugs for example, nucleoside reverse transcriptase
      inhibitor (NRTI) rather than lamivudine, abacavir etc. The data were analyzed
      using univariate Poisson regression. RESULTS: The anonymized records of 3302
      individual patients who attended in 11 separate regions were scrutinized. Sixty
      eight different combinations of antiretroviral regimes were identified. The
      prescribing patterns for the five most frequently prescribed regimes in the four
      largest clinics are shown in Table 1, along with the overall percentage of
      patients with undetectable VL. A higher proportion of patients in Scotland who
      are prescribed regimes of NRTI*2 or NRTI/NtRTI plus PI have detectable VL but
      this is not statistically significant. Although the percentage of patients with
      VL<50 varies between regions 1 and 4 versus regions 2 and 3, this is also not
      statistically significant. CONCLUSIONS: Overall, a high proportion of Scottish
      patients on ART have undetectable VL. Patterns of ART prescribing in Scotland do
      vary by region but there are no significant differences in outcome with regard to
      undetectable VL. There is a non-significant trend which may be accounted for by
      differing levels of PI prescribing.

PMID- 25394119
TI  - Determinants of HIV-1 drug resistance in treatment-naive patients and its
      clinical implications in an antiretroviral treatment program in Cameroon.
AB  - INTRODUCTION: Facing the rapid scale-up of antiretroviral treatment (ART)
      programs in resource-limited settings, monitoring of treatment outcome is
      essential in order to timely detect and tackle drawbacks [1]. METHODS: In a
      prospective cohort study, 300 consecutive patients starting first-line ART were
      enrolled between 2009 and2010 in a large HIV treatment centre in rural Cameroon.
      Patients were followed up for 12 months. Virologic failure was defined as a VL
      >1000 cop/mL at month 12. Besides CD4 and viral load (VL) analysis, HIV-1 drug
      resistance testing was performed in patients with VL>1000 copies (c)/mL plasma.
      In those patients and controls, minority HIV-1 drug resistance mutations at
      baseline, and plasma drug levels were analyzed in order to identify the risk
      factors for virologic failure. RESULTS: Most enrolled patients (71%) were female.
      At baseline median CD4 cell count was 162/uL (IQR 59-259), median log10 VL was
      5.4 (IQR 5.0-5.8) c/mL, and one-third of patients had World Health Organisation
      (WHO) stage 3 or 4; 30 patients died during follow-up. Among all patients who
      completed follow-up 38/238 had virologic failure. These patients were younger,
      had lower CD4 cell counts and more often had WHO stage 3 or 4 at baseline
      compared to patients with VL<1000c/mL. Sixty-three percent of failing patients
      (24/38) had at least one mutation associated with high-level drug resistance. The
      M184V mutation was the most frequently detected nucleoside reverse transcriptase
      inhibitor (NRTI) mutation (n=18) followed by TAMs (n=5) and multi-NRTI resistance
      mutations (n=4). The most commonly observed non-nucleoside reverse-transcriptase
      inhibitor (NNRTI) resistance mutations were K103N (n=10), Y181C (n=7), and G190A
      (n=6). Drug resistance mutations at baseline were detected in 12/65 (18%)
      patients, in 6 patients with and 6 patients without virological failure (p=0.77).
      Subtherapeutic NNRTI levels (OR 6.67, 95% CI 1.98-22.43, p<0.002) and poorer
      adherence (OR 1.54, 95% CI 1.00-2.39, p=0.05) were each associated with higher
      risk of virologic failure in the matched pair analysis. Unavailability of ART at
      the treatment centre was the single most common cause (37%) for incomplete
      adherence in these patients. CONCLUSIONS: Virologic failure after one year of
      first-line ART in rural Cameroon was not associated with transmitted drug
      resistance, but with reduced drug plasma levels and incomplete adherence.
      Strategies to assure adherence and uninterrupted drug supply are important
      factors for therapy success.

PMID- 25394120
TI  - Reduced HIV symptoms and improved health-related quality of life correlate with
      better access to care for HIV-1 infected women: the ELLA study.
AB  - INTRODUCTION: Global HIV-1 prevalence is 35.3 million [1]; women comprise >50% of
      those infected. The majority of women may lack regular care and only one-fourth
      are virologically suppressed [2]. ELLA is a cross-sectional, non-interventional
      study conducted across Europe, Latin America, Canada and Asia that describes
      barriers to care for HIV-infected women and associations with disease stage,
      symptoms and health-related quality of life (HRQoL). METHODS: HIV-infected women
      eligible for ELLA (>=18 years) completed: Barrier to Care Scale (BACS) comprising
      12 items in four domains (Index range 0-12, Overall range 1-4, greater=more
      barriers, Overall score >=2 considered severe); AIDS Clinical Trials Group (ACTG)
      Health Status Assessment comprising 21 items assessing 9 HRQoL domains (range 0
      100, greater=better); and ACTG Symptom Distress Module comprising 20 symptoms
      rated on bother (range 0-4, greater=more bother). Healthcare providers documented
      medical history and HIV clinical data. Correlations of BACS response and last
      reported VL/CD4 count with HIV symptoms and HRQoL were analyzed. Spearman rank
      order was used to test correlations with statistical significance set at p<0.05.
      RESULTS: Enrollment: 1931 women from 30 countries; mean age 40 years (16.9% >50
      years); 47.7% education <12 years; 36% unemployed; 82.9% urban residence. HIV was
      acquired heterosexually in 83.0%; 88.2% of subjects were on ART; 57.5% had VL<50
      c/ml; mean CD4 was 540.5 c/uL. Mean [SD] BACS Index and Overall scores were 6.19
      [3.47] (N=1818) and 2.09 [0.71] (N=1922), respectively. Stigma was a prominent
      barrier. Lower (better) BACS Index and Overall scores correlated with better
      HRQoL on all nine domains (p<0.0001). Lower VL and greater CD4 count were both
      correlated with better HRQoL for eight of nine domains (p<0.04, p<=0.0002,
      respectively) excepting pain. Lower BACS Index and Overall scores correlated with
      fewer symptom count and less symptom bother (p<0.0001). Fewer symptom count and
      less symptom bother correlated with better HRQoL on all nine domains (p<0.0001).
      While greater CD4 count correlated with fewer HIV symptoms and less bother
      (p<0.0001), VL did not significantly correlate with either. CONCLUSIONS: In HIV
      infected women, reduced barriers to care correlated with fewer symptoms, less
      symptom bother and better HRQoL. Improved HRQoL may be mediated by greater CD4
      counts and fewer symptoms. Better access to care may improve HRQoL outcomes in
      this population.

PMID- 25394121
TI  - Analysis of causes of death among HIV-infected patients of Kiev Regional AIDS
      Center during 2013.
AB  - Ukraine is a leader in Europe in the prevalence of HIV infection. There are up to
      270 thousand people, who are living with HIV. Since 1987, in Ukraine, 33,149 HIV
      infected people died. During the first six months of 2013, of all the dead, who
      were suffering from HIV and in need of antiretroviral treatment (ART) at the time
      of death, 41% received treatment and only 5.7% received ART for more than one
      year. Specialists of Kiev Regional AIDS Center analyzed mortality among the
      patients of the centre, in order to determine the most frequent cause of death,
      set the group most at risk and to develop effective measures to reduce mortality
      among HIV-infected patients. In Kiev AIDS Center, 10,000 people are under medical
      observation and 4004 of them are taking ART. During 2013, 305 persons died: 217
      were women and 88 were men which included 3 children under 14 years. Most of the
      dead - 272 (89%) were aged 25-49. Among the total number of the dead, 125 people
      (41%) were receiving ART, 53 of them (17%) were receiving ART for at least one
      year and 39 of them (13%) were receiving ART for less than one month. Hundred and
      fifty-eight people (52%) required ART and 22 (7%) did not need therapy. Hundred
      and ninety-two patients (63%) were in four clinical stage of HIV infection.
      Hundred and ten of them had HIV+TB co-infection. Twenty patients died due to TB
      and 12 patients died due to hepatitis b virus/hepatitis c virus (HBV/HCV). Among
      these patients, 87 people (39%) were taking ART and 136 persons (61%) were in
      need of ART, but did not get it. Nineteen patients were diagnosed with cancer.
      Sixteen patients, who were co-infected HIV+TB had a CD4 cell count of more than
      300. Based on this analysis, we can conclude that the main causes of high
      mortality among HIV-infected patients in 2013 were late diagnosis of HIV, besides
      a large number (52%) of patients, who were in need of ART did not take it. A
      large number (40%) among those who died were patients co-infected with HIV+TB,
      HIV+HBV/HCV. This reinforces the necessity to introduce new schemes for the
      integrated treatment of these patients, including patients with MDR, XDR TB. Also
      all HIV-infected patients who died in 2013, were diagnosed multiple pathology of
      various organs, which demonstrates the necessity of the introduction of schemes
      of early diagnosis and approaches to treatment of this disease. A large number of
      deaths (24%) of patients receiving ART for more than a year, highlight the
      necessity for changes to existing treatment regimen in HIV patients, with the
      possibility of the development of viral resistance to certain drugs and taking
      into account the latest international experience in the treatment of HIV-infected
      patient. 

PMID- 25394122
TI  - Stigma reduces and social support increases engagement in medical care among
      persons with HIV infection in St. Petersburg, Russia.
AB  - INTRODUCTION: The proportion of people living with HIV (PLH) in care and on
      antiretroviral therapy (ART) in Russia is lower than in Sub-Saharan Africa (1).
      This is undoubtedly due to a variety of systems and structural issues related to
      poor treatment access, linkage and care delivery models. However, little research
      has explored the reasons that PLH are not in care from their own perspectives.
      This information can help to guide the development of approaches for improving
      HIV care engagement in the country. MATERIALS AND METHODS: In-depth interviews
      were undertaken with 80 PLH in St. Petersburg who had never been in HIV medical
      care, had previously been out of care, or had always been in care. Participants
      were recruited through online PLH forums and Websites, outreach needle exchange
      and non-government organisation (NGO) programs, and chain referral. The
      interviews elicited detailed information about participants' experiences and
      circumstances responsible for being out of care, and factors contributing to
      nonretention in HIV treatment. Verbatim transcriptions of the interviews were
      coded and analyzed using MAXQDA software to identify emerging themes. RESULTS:
      Two types of care engagement barriers most often emerged. Some related to medical
      services, and others to the family and social environment. The most frequent
      medical service barriers were poor treatment infrastructure conditions and
      access; dissatisfaction with quality of services and medical staff; and concerns
      over confidentiality and HIV status disclosure. Social barriers were fears of
      potential harm to family relationships, negative consequences if status became
      known at work, and public stigmatization and myths associated having an HIV+
      status. Social support from the PLH community and from family and close friends
      facilitated care engagement, as did motivation to take care of oneself and one's
      family. Most participants also described circumstances in which engaging into HIV
      care was brought about by an urgent issue (opportunistic infections) or was
      enforced through hospitalization or imprisonment. Trust in one's doctor and
      simply not wanting to die were also common motives. CONCLUSIONS: Stigma was a
      major barrier to care engagement, including fear that others would learn of one's
      HIV+ status, whether at work, in one's family, or in the general community. By
      contrast, support from family, friends and the PLH community contributed to care
      engagement.

PMID- 25394123
TI  - Early HIV diagnosis through use of rapid diagnosis test (RDT) in the community
      and direct link to HIV care: a pilot project for vulnerable populations in
      Athens, Greece.
AB  - INTRODUCTION: An increase in the incidence of HIV new infections among
      intravenous drug users (IDUs) by 1500%, was noted in the center of Athens in
      2011. Increasing problematic drug use, homelessness, health cuts amidst the
      economic crisis, have contributed to the epidemic. New cases doubled within a
      year, challenging the HIV care delivery system (1). MATERIALS AND METHODS: A
      pilot project funded by the National Strategic Reference Framework (NSRF) 2007
      2013 of the European Union (EU), was launched from August 2012 to March 2014. It
      was a partnership between the HIV Clinic of Evangelismos Hospital and the NGO
      PRAKSIS. The project is aimed at offering early diagnosis and comprehensive care
      to hard to reach populations. RDT diagnosis through mobile units, direct linkage
      to care, elimination of waiting times, flexibility, psychosocial support and link
      to harm reduction services for active IDUs were offered to the beneficiaries.
      RESULTS: A total of 117 people enrolled in the program following HIV RDT offered
      by mobile units of the NGO PRAKSIS in community sites. Sixty-eight percent were
      IDUs, 12% were men who have sex with men (MSM) and 19.5% were heterosexuals. Men
      were 74.3% and women were 25.6%. Country born patients were 43.5% and non-country
      born patients were 56.4%. Nine people were HIV negative but needed post-exposure
      prophylaxis (PEP), treatment for Hepatitis C and one test was false positive. Two
      deaths occurred and six people were deported. Of the remaining 100 patients, 84
      enrolled in the care program. Of those 77% (65/84) remain in care for three
      months after the end of the project. Care retention was 73.5% (39/53) for IDUs,
      91% (10/11) for MSM, 80% (16/20) for heterosexuals, 73% (25/35) for country born
      and 82% (40/49) for non-country born individuals. Among those that remain in
      care, 77.7% (42/54) with <350 CD4 are on antiretroviral therapy (ART). Among
      those on ART >90% have undetectable viral load. Mean value of CD4 cells at
      enrollment was 298 cells/mm(3). At follow up, three months after the end of the
      program, the mean value of CD4 cells was 464 cells/mm(3). CONCLUSIONS: The
      project has proven the feasibility of a novel approach of active case finding in
      the community with direct link to care. Retention to care was satisfactory as
      most of those patients would not have been able to access care through the normal
      ART delivery mode of the Public Health System. However, more obstacles to care
      remain. Being homeless, poor nutrition, complicated access to harm reduction
      services, lack of One Stop Shop services and police operations in the city center
      impede further progress [2,3].

PMID- 25394124
TI  - HIV/AIDS mortality in a south east European country versus a west European
      country.
AB  - INTRODUCTION: Antiretroviral (ARV) treatment available in low-middle income
      countries differs as suggested in international HIV-treatment guidelines. Thus,
      we compared ARV regimens introduced as a first-line therapy, time of initiation,
      frequency of making combination antiretroviral therapy (cART) switches, frequency
      of viral and immunological monitoring and treatment outcome in south east
      European (SEE) country (i.e. HIV Centre in Belgrade, Serbia, (HCB)) and west
      European country (i.e. Royal Free Centre for HIV Medicine at the Royal Free
      Hospital London, UK (RFH)). MATERIALS AND METHODS: ARV naive patients starting
      cART from 2003 to 2012 were included. Comparisons of the two cohorts were made
      using a chi-square test or Fisher's exact test for categorical variables and a
      Mann-Witney U test for continuous variables. Kaplan Meier survival curves were
      compared using the log rank test. RESULTS: Of 597 patients from HCB, 361 (61%)
      initiated cART with prior AIDS diagnosed, while 337 (19%) of 1763 patients from
      RFH. Average baseline CD4+ T cell counts were significantly lower in Serbia than
      in UK (177 cells/mm(3) vs 238 cells/mm(3)). The total (mediana, IQR) CD4+ T cell
      count measurements in the first year of cART was 2 (1, 2) at the HCB, while it
      was statistically significant higher at the RFH 5 (3, 7), respectively
      (p<0.0001). At the RFH, it appeared that the cART switching is due to patient's
      preference or toxicity (46%), while the lack of supply and toxicity (37%) were
      the most important reasons for treatment change in HCB, within the same period of
      time (p<0.05). Mortality rates were higher at the HCB versus RFH (p<0.0001).
      After 12, 24 and 36 months of cART, 3%, 5% and 8% of patients died in HCB,
      whereas 2%, 3% and 4% of patients died in RFH, respectively (Figure 1).
      CONCLUSIONS: In south European countries, as a consequence of low testing rate,
      ARV treatment is introduced at an advanced stage of disease, having a high
      mortality rate as a consequence. Switching within ARV drugs appears often due to
      lack of drug supplies and frequently drug-related toxicity in south east Europe,
      while in the east European country due to patient's preferences and rarely due to
      drug-related toxicity.

PMID- 25394125
TI  - AIDS defining opportunistic infections in patients with high CD4 counts in the
      combination antiretroviral therapy (cART) era: things ain't what they used to be.
AB  - INTRODUCTION: According to reports from observational databases, classic AIDS
      defining opportunistic infections (ADOIs) occur in patients with CD4 counts above
      500/uL on and off cART. Adjudication of these events is usually not performed.
      However, ADOIs are often used as endpoints, for example, in analyses on when to
      start cART. MATERIALS AND METHODS: In the database, Swiss HIV Cohort Study (SHCS)
      database, we identified 91 cases of ADOIs that occurred from 1996 onwards in
      patients with the nearest CD4 count >500/uL. Cases of tuberculosis and recurrent
      bacterial pneumonia were excluded as they also occur in non-immunocompromised
      patients. Chart review was performed in 82 cases, and in 50 cases we identified
      CD4 counts within six months before until one month after ADOI and had chart
      review material to allow an in-depth review. In these 50 cases, we assessed
      whether (1) the ADOI fulfilled the SHCS diagnostic criteria (www.shcs.ch), and
      (2) HIV infection with CD4 >500/uL was the main immune-compromising condition to
      cause the ADOI. Adjudication of cases was done by two experienced clinicians who
      had to agree on the interpretation. RESULTS: More than 13,000 participants were
      followed in SHCS in the period of interest. Twenty-four (48%) of the chart
      reviewed 50 patients with ADOI and CD4 >500/uL had an HIV RNA <400 copies/mL at
      the time of ADOI. In the 50 cases, candida oesophagitis was the most frequent
      ADOI in 30 patients (60%) followed by pneumocystis pneumonia and chronic
      ulcerative HSV disease (Table 1). Overall chronic HIV infection with a CD4 count
      >500/uL was the likely explanation for the ADOI in only seven cases (14%). Other
      reasons (Table 1) were ADOIs occurring during primary HIV infection in 5 (10%)
      cases, unmasking IRIS in 1 (2%) case, chronic HIV infection with CD4 counts
      <500/uL near the ADOI in 13 (26%) cases, diagnosis not according to SHCS
      diagnostic criteria in 7 (14%) cases and most importantly other additional immune
      compromising conditions such as immunosuppressive drugs in 14 (34%). CONCLUSIONS:
      In patients with CD4 counts >500/ uL, chronic HIV infection is the cause of ADOIs
      in only a minority of cases. Other immuno-compromising conditions are more likely
      explanations in one-third of the patients, especially in cases of candida
      oesophagitis. ADOIs in HIV patients with high CD4 counts should be used as
      endpoints only with much caution in studies based on observational databases.

PMID- 25394126
TI  - Investigating barriers in HIV-testing oncology patients. The IBITOP study: phase
      I.
AB  - BACKGROUND: Since the advent of combined antiretroviral therapy (ART), the
      incidence of non-AIDS-defining cancers (non-ADCs) among HIV-positive patients is
      rising. We previously described HIV testing rates of <5% in our oncology centre,
      against a local HIV prevalence of 0.4% (1). We have since worked with the Service
      of Oncology to identify, how HIV testing can be optimized, we have conducted a
      study on investigating barriers in HIV-testing oncology patients (IBITOP) among
      treating oncologists and their patients. METHODS: After an initial two-month
      pilot study to examine feasibility (2), we conducted the first phase of the
      IBITOP study between 1st July and 31st October 2013. Patients of unknown HIV
      status, newly diagnosed with solid-organ non-AIDS-defining cancer, and treated at
      Lausanne University Hospital were invited to participate. Patients were offered
      HIV testing as a part of their initial oncology work-up. Oncologist testing
      proposals and patient acceptance were the primary endpoints. RESULTS: Of 235
      patients with a new oncology diagnosis, 10 were excluded (7 with ADCs and 3 of
      known HIV-positive status). Mean age was 62 years; 48% were men and 71% were
      Swiss. Of 225 patients, 75 (33%) were offered HIV testing. Of these, 56 (75%)
      accepted, of whom 52 (93%) were tested. A further ten patients were tested
      (without documentation of being offered a test), which gave a total testing rate
      of 28% (62/225). Among the 19 patients who declined testing, reasons cited
      included self-perceived absence of HIV risk, previous testing and palliative
      care. Of the 140 patients not offered HIV testing and not tested, reasons were
      documented for 35 (25%), the most common being previous testing and follow-up
      elsewhere. None of the 62 patients HIV tested had a reactive test. CONCLUSIONS:
      In this study, one third of patients seen were offered testing and the HIV
      testing rate was fivefold higher than that of previously observed in this
      service. Most patients accepted testing when offered. As HIV-positive status
      impacts on the medical management of cancer patients, we recommend that HIV
      screening should be performed in settings, where HIV prevalence is >0.1%. Phase
      II of the IBITOP study is now underway to explore barriers to HIV screening among
      oncologists and patients following the updated national HIV testing guidelines
      which recommend testing in non-ADC patients undergoing chemotherapy.

PMID- 25394127
TI  - Profile and mortality outcome of patients admitted with cryptococcal meningitis
      to an urban district hospital in KwaZulu-Natal, South Africa.
AB  - INTRODUCTION: Cryptococcal meningitis (CCM) is one of the leading causes of early
      mortality among HIV-infected patients. This study was a part of clinical audit
      (1) aimed at improving care for patients with CCM at an urban district hospital
      in South Africa. METHODS: Clinical records of all patients (age>13 years)
      admitted to the hospital with a diagnosis of CCM (based on a positive India ink,
      positive cryptococcal latex agglutination test (CLAT) or a positive culture of
      Cryptococcus neoformans) between June 2011 and December 2012 were retrospectively
      reviewed. Descriptive statistics and Chi-square analysis were generated with Epi
      Info 7.1.2.0. 95% confidence intervals were reported where appropriate. RESULTS:
      Of the 127 patients admitted with CCM, only 97 (76.4%) knew their HIV status.
      Only 44.8% (43/96) of those who knew they were HIV positive were on
      antiretroviral therapy (ART). Seventeen out of 25 patients (68%) previously
      treated for CCM had defaulted fluconazole and only 60% (15/25) were on ART. Acute
      mortality (death within 14 days of CCM diagnosis) was 55.9% (71/127). The median
      time to death from diagnosis was four days (IQR 2-9). The association between CSF
      WBC count<20cells/mL and increased risk of death within 14 days was statistically
      significant (OR 2.2; 95% CI 1.1-4.6, p=0.03). Patients with heavy cryptococcal
      burden (reported as numerous yeasts seen on microscopy) at diagnosis were three
      times more likely to die within 14 days of diagnosis of CCM (OR 3.2; 95% CI 0.9
      10.7, p=0.06). Even though a CD4 count<100cells/mm(3) was associated with a 1.6
      times increased acute mortality risk, the association was not statistically
      significant (OR 1.6; 95% CI 0.6-4.6, p=0.3). The role of elevated CSF opening
      pressure at diagnosis was not assessed because only two (1.6%) patients had their
      baseline opening pressure measured. CONCLUSIONS: Acute CCM-related mortality
      remains high. The number of patients who do not know their HIV status, the number
      of HIV positive patients not on ART, the high level of non-adherence to
      fluconazole and the proportion of patients not on ART after at least one previous
      CCM episode all point to the need of developing comprehensive strategies aimed at
      encouraging HIV testing and improving patient's retention in HIV care and
      support.

PMID- 25394128
TI  - Improved outcomes from HIV/TB co-infection in Singapore following a switch to
      earlier anti-retroviral therapy.
AB  - INTRODUCTION: Recent clinical trials have provided clear evidence to support
      early anti-retroviral therapy (ART) in patients with HIV/TB co-infection and low
      CD4 counts. We investigated how this has changed treatment and outcomes in
      Singapore. MATERIALS AND METHODS: A retrospective review was performed with
      inpatient and outpatient records for all subjects diagnosed with HIV/TB co
      infection from 2006 to 2011 attending the Tuberculosis Control Unit, Tan Tock
      Seng Hospital, Singapore. Data for subjects with a presenting CD4<200 cell/mm(3)
      were extracted and split into two groups, "Delayed": ART more than 8/52 after
      starting TB treatment, and "Early": ART within 8/52 of starting TB treatment.
      RESULTS: One hundred thirty-four out of 180 subjects in the database met the
      inclusion criteria for this study, 89 in the delayed group and 45 in the early.
      No statistically significant differences in baseline demographics between the two
      groups were identified. Both groups presented with markedly low CD4 counts, with
      overall 60% <50cells/mm(3). Median CD4 counts were lower in the delayed ART group
      (37 vs 50, p=0.015). Prevalence of other opportunistic infections at TB diagnosis
      was not significantly different (20%), but TB in the early ART group was more
      likely to include extra-pulmonary disease (46% vs 57%, p=0.038). Four cases were
      culture negative, 2 multi-drug resistant and 10 (7.8%) were isoniazid mono
      resistant. There was a significant trend to earlier ART with more recent TB
      diagnosis (p<0.001). In the first 365 days after TB diagnosis, 11 deaths occurred
      in the delayed ART group, and 0 in the early (p=0.033). A Kaplan-Meier time-to
      event analysis demonstrated a clear separation in the frequency of death or
      opportunistic infections at eight weeks (Figure 1, p<0.001). Immune
      reconstitution disease was significantly more likely in the early ART group, but
      did not result in death (9% vs 38%, p<0.001). Treatment interruptions due to
      adverse drug events (ADE) developed in a median of 25 days (IQR 15-43).
      Interestingly, early ART was associated with a significantly lower number of
      treatment interruptions attributed to ADEs, with a higher proportion of patients
      completing two months of pyrazinamide induction (66% vs 85%, p=0.054) and
      rifampicin consolidation (79% vs 95%, p=0.03) - after excluding resistance or
      death. A trend to longer duration TB treatment was observed with delayed ART.
      CONCLUSIONS: Significant improvements in HIV/TB infection outcomes correlate with
      the switch to earlier ART.

PMID- 25394129
TI  - Alarming increase in tuberculosis and hepatitis C virus (HCV) among HIV infected
      intravenous drug users.
AB  - INTRODUCTION: In the last years, we observed an alarming increase in the number
      of newly diagnosed HIV infected intravenous drug users (IDUs) co-infected with
      hepatitis viruses or with severe bacterial infections. The aim of our study was
      to assess the incidence, the demographic and clinical characteristics of IDUs
      diagnosed with HIV, HCV and tuberculosis (TB). MATERIALS AND METHODS: Prospective
      study on HIV infected IDUs with HCV and TB admitted in a single centre between
      January 2009 and April 2014. Data were compared to a group of HIV infected IDUs
      without TB. Statistical analysis was performed using Graphpad Prism 4.01.
      RESULTS: Out of 450 HIV infected IDUs, 134 (29.7%) were diagnosed with HIV, HCV
      and TB. TB incidence among IDUs increases from 0% in 2009 to 30.2% in 2013. The
      TB coinfected patients had a mean age at diagnosis of 30 [15-56] years; were in
      majority males, 106 (84.4%); from urban areas, 120 (89.5%); and had significantly
      lower education level (85% vs 68.3%, p<0.0001) and higher rates of unemployment
      (80% vs 55%, p<0.0001) than those without TB. The median CD4 cell count was lower
      in the TB versus non TB IDUs (143 vs 472/mm(3), p<0.0001). TB infected IDUs tend
      to be more frequently late presenters (59.7 vs 24.6, p<0.0001) and to have
      advanced HIV disease (47.7 vs 7.59%, p<0.0001) than those without TB. TB cultures
      were positive in 64 (47.7%) patients, 3 (2.2%) had multidrug resistant TB and 2
      (1.5%) had extended drug resistance. Disseminated and/or extrapulmonary TB was
      diagnosed in 51 patients (38%). The overall mortality rate was higher in TB
      compared to non TB IDUs (19.4% vs 8.2%, p=0.0007), disseminated TB being
      associated with the most severe immunosuppression (median CD4 cell count
      42/mm(3)) and the highest mortality rate (27.4%). CONCLUSIONS: The incidence of
      TB in HIV/HCV coinfected IDUs was high and rose over the time. TB infection was
      more frequent in patients with severe immunosuppression and the mortality rate
      was higher in IDUs with disseminated and/or extrapulmonary disease. IDUs are
      important candidates for acquiring and transmitting HIV infection, viral
      hepatitis and TB, being difficult to control due to their high-risk behaviours.
      Strengthening of HIV transmission prevention strategies, particularly in
      identified risk groups, is mandatory.

PMID- 25394130
TI  - Telaprevir combination therapy in HCV/HIV co-infected patients (INSIGHT study):
      sustained virologic response at 12 weeks final analysis.
AB  - INTRODUCTION: We report the SVR12 final analysis of a phase 3 study of telaprevir
      in combination with peginterferon (P)/ribavirin (R) in HCV-genotype 1, treatment
      naive and -experienced patients with HCV/HIV co-infection (INSIGHT). MATERIALS
      AND METHODS: Patients receiving stable, suppressive HIV antiretroviral (ARV)
      therapy, containing atazanavir/ritonavir, efavirenz, darunavir/ritonavir,
      raltegravir, etravirine or rilpivirine, received telaprevir 750 mg q8h (1125 mg
      q8h if on efavirenz) plus P (180 ug once-weekly) and R (800 mg/day) for 12 weeks,
      followed by an additional 12 weeks (non-cirrhotic HCV treatment-naive and relapse
      patients with extended rapid viral response [eRVR]) or 36 weeks (all others) of
      PR alone. Analysis was performed when all patients had completed the follow-up
      visit of 12 weeks after last planned dose. RESULTS: One hundred sixty-two
      patients were enrolled and treated (65 efavirenz, 59 atazanavir/ritonavir, 17
      darunavir/ritonavir, 17 raltegravir, 4 etravirine). Mean age was 45 years, 78%
      were male, 92% were Caucasian; mean CD4 count was 687 cells/mm(3). Sixty four
      patients (40%) were HCV treatment-naive and 98 (60%) were treatment experienced
      (29 relapsers, 18 partial responders and 51 null responders). 64% were subtype
      1a. 30% had bridging fibrosis (17%) or cirrhosis (13%). 19% of patients
      discontinued telaprevir, including 9% due to an adverse event (AE), 8% reaching a
      virologic endpoint and 2% for other reasons (non compliance or not defined).
      Treatment responses are shown in Table 1. There were no HIV RNA breakthroughs.
      Most frequently reported (>=20% patients) AEs were pruritus 43%; fatigue 27%;
      rash 34%, anorectal events 30% and influenza-like illness (25%). Anemia was
      reported in 15% of patients; grade >=3 haemoglobin decrease occurred in 2.5% of
      patients. 6% of patients experienced serious AEs. CONCLUSIONS: In this phase 3
      study of HIV-infected, HCV treatment-naive and -experienced patients, 49%
      achieved eRVR and 57% reached SVR12. In patients with an eRVR, SVR12 rates were
      >80%, irrespective of prior treatment history.

PMID- 25394131
TI  - Monitoring renal function during combination therapy with telaprevir in HIV/HCV
      co-infected patients with advanced/fibrosis cirrhosis.
AB  - INTRODUCTION: Telaprevir (TVR) plus peg interferon (PEG-IFN) and ribavirin (RBV)
      substantially increase treatment efficacy for genotype 1 chronic hepatitis C
      virus (HCV) infection but data about its safety in HIV patients with cirrhosis
      are lacking. Our purpose was to evaluate estimated Glomerular Filtration Rates
      (eGFR) variations during combination therapy in a difficult-to-treat HIV/HCV
      population with advanced fibrosis/cirrhosis through three different scores
      commonly used in clinical practice: CKD-EPI (Chronic Kidney Disease Epidemiology
      Collaboration), Modification of Diet in Renal Disease (MDRD) scores (that
      consider gender, ethnicity, age, serum creatinine level [SCL]) and MDRD 6
      variable (that considers the previous parameters plus blood urea nitrogen and
      serum albumin). Second objective was to identify any association between
      creatinin clearance and haemoglobin (Hb) variation during combination therapy.
      MATERIALS AND METHODS: We conducted an observational retrospective study
      including 18 HIV/HCV patients attending our clinic who started combination
      therapy for HCV, including in the analysis the first 16 weeks of therapy.
      Treatment included TVR 1125 mg BID (twice a day) for 12 weeks, PEG-IFN alpha-2a
      180 mcg QW and RBV daily dose according to body weight (800 mg in individuals <60
      kg; 1000 mg in individuals 60-75 kg; 1200 mg in individuals >75 kg). Advanced
      fibrosis was defined as Metavir score=F3 or Ishak 3-4 and cirrhosis was defined
      as Metavir score F4 or Ishak 5-6 assessed by liver biopsy or transient
      elastography respectively. P per trend were assessed to evaluate any change of
      SCL and eGFR (according to different formulas). Multilevel linear regression
      analysis was performed to estimate factors associated with reduction of Hb.
      RESULTS: Baseline characteristics and HCV virological responses were collected.
      Figure 1 shows median SCL and eGFR trends across follow-up period: SCR p-per
      trend was 0.28, for CKD-EPI was 0.50, for MDRD was 0.48, for MDRD-6 variables was
      0.27. Hb trend was also assessed and a significant decrease of Hb across follow
      up (p per trend <0.001) was noted. Multilevel regression analysis found an
      association between SCL and Hb change, after adjustment for age, sex, basal BMI,
      tenofovir exposure and proteinuria (assessed at baseline) as shown in Table 1.
      CONCLUSIONS: In our experience, combination therapy with TPV in cirrhotic HIV-HCV
      patients did not significantly affect renal function. As expected, Hb levels
      decreased during treatment and it is likely related to RBV exposure. In
      multivariable analysis, reduction of Hb appeared to be related to SCL higher
      levels, thus suggesting even a mild decrease of renal function.

PMID- 25394132
TI  - Evaluation of drug-drug interaction between daclatasvir and methadone or
      buprenorphine/naloxone.
AB  - INTRODUCTION: Daclatasvir (DCV) is a potent hepatitis C virus (HCV) NS5A
      replication complex inhibitor with pangenotypic (1-6) activity in vitro.
      Methadone (MET) and buprenorphine (BUP) are opioid medications used to treat
      opioid addiction; patients on HCV therapy may require MET or BUP treatment. The
      effect of DCV on the pharmacokinetics (PK) of MET or BUP/naloxone (NLX) was
      assessed in subjects on stable MET or BUP. MATERIALS AND METHODS: An open-label,
      two-part study assessed the effect of steady-state oral administration of DCV on
      the PK of MET (Part 1, P1) or BUP/NAL (Part 2, P2). Safety/tolerability and
      pharmacodynamics (PD, opioid withdrawal scales/overdose assessment) were also
      assessed. Subjects (P1, N=14; P2, N=11) received daily single-dose oral MET (40
      120mg) or BUP/NLX (8/2-24/6mg) based on their prescribed stable dose throughout,
      in addition to DCV (60mg QD) on Days 2-9. Serial PK sampling occurred predose and
      postdose till 24 hours on Day 1 (MET/BUP) and Day 10 (MET/BUP/DCV).
      Noncompartmental PK were derived. Geometric mean ratios (GMR) and 90% confidence
      intervals (90% CI) for MET/BUP/norBUP Cmax and AUCTAU were derived from linear
      mixed effects models. RESULTS: Subjects were aged 19-39 years, mostly white (P1,
      93%; P2, 100%) and male (P1, 71%; P2, 91%). All subjects completed the study. No
      clinically meaningful effect was demonstrated as the GMR and 90% CIs fell within
      the prespecified interval (P1, 0.7-1.4; P2, 0.5-2.0: see Table 1). DCV
      coadministration was well-tolerated: overall, six (43%) subjects had adverse
      events (AEs) (all mild and resolved without treatment). DCV had no clinically
      significant effect on the PD of MET or BUP/NLX. CONCLUSIONS: Steady-state
      administration of DCV 60mg QD had no clinically meaningful effect on the PK of
      MET or BUP/NLX and was generally well-tolerated, suggesting that no dose
      adjustments will be required.

PMID- 25394133
TI  - HCV triple therapy in co-infection HIV/HCV is not associated with a different
      risk of developing major depressive disorder.
AB  - INTRODUCTION: Hepatitis C (HCV) treatment options have changed with the
      development of direct activity antivirals (DAAs) and the availability of triple
      therapies have improved HCV cure rates. A common neuropsychiatric side effect of
      pegylated-interferon and ribavirin treatment is major depressive disorder (MDD),
      however little is known about such adverse events with protease inhibitor-based
      triple therapy. The aim of this study was to assess the rate of MDD in co
      infected HIV HCV patients undergoing different HCV treatments. METHODS: All
      participants were co-infected HIV HCV attending the Royal Sussex County Hospital
      Brighton hepatology outpatient clinic between 2010 and 2014. Participants were
      assessed for DSM-IV MDD and depression severity (using the Hamilton depression
      scale (HAMD)) at baseline and monthly after treatment initiation. HIV and HCV
      stages, genotype, reinfection and standard demographic variables were recorded.
      Influence of HCV stage (acute vs. chronic) and type of treatment (classic vs
      triple), emergence of MDD and clearance outcomes were analyzed using repeated
      measures and logistic regression models. RESULTS: Fifty participants with a mean
      age of 42.65 years (SD=10.32) were included; most were male (98%). The majority
      had contracted HCV genotype 1 (64%) or 4 (26%). The HCV stage and treatment
      groups were matched for age and depression at baseline. No significant
      differences were found on virological outcomes considering HCV stage and
      treatment. From baseline to SVR, there was a significant increase in HAMD scores,
      F(4,36)=10.09, p<.001; this was not significantly influenced by HCV stage,
      F(4,35)=0.54, p=.708 or HCV treatment group, F(4,35)=0.60, p=.664. Those with
      chronic HCV were more likely to transition to MDD than acute infection (OR 7.77,
      95% CI 2.04-29.54, p=.003). No differences were found for depression emergence by
      HCV treatment group (OR 0.83, 95% CI 0.22-3.13, p=.787). CONCLUSIONS: HCV triple
      therapy was not associated with a different risk of emergence of MDD versus
      classic treatment. MDD should be assessed before therapy initiation and monitored
      throughout treatment for any HCV treatment regime. Future research could usefully
      clarify mechanisms of MDD emergence and risk factors for this.

PMID- 25394134
TI  - Sexual behaviour, recreational drug use and hepatitis C co-infection in HIV
      diagnosed men who have sex with men in the United Kingdom: results from the ASTRA
      study.
AB  - INTRODUCTION: Transmission of Hepatitis C virus (HCV) among HIV-positive men who
      have sex with men (MSM) in the United Kingdom is ongoing. We explore associations
      between self-reported sexual behaviours and drug use with cumulative HCV
      prevalence, as well as new HCV diagnosis. METHODS: ASTRA is a cross-sectional
      questionnaire study including 2,248 HIV-diagnosed MSM under care in the United
      Kingdom during 2011-2012. Socio-demographic, lifestyle, HIV-related and sexual
      behaviour data were collected during the study. One thousand seven hundred and
      fifty two (>=70%) of the MSM who consented to linkage of ASTRA and clinical
      information (prior to and post questionnaire) were included. Cumulative
      prevalence of HCV was defined as any positive anti-HCV or HCV-RNA test result at
      any point prior to questionnaire completion. We excluded 536 participants with
      clinical records only after questionnaire completion. Among the remaining 1,216
      MSM, we describe associations of self-reported sexual behaviours and recreational
      drug use in the three months prior to ASTRA with cumulative HCV prevalence, using
      modified Poisson regression with robust error variances. New HCV was defined as
      any positive anti-HCV or HCV-RNA after questionnaire completion. We excluded 591
      MSM who reported ever having a HCV diagnosis at questionnaire, any positive HCV
      result prior to questionnaire or did not have any HCV tests after the
      questionnaire. Among the remaining 1,195 MSM, we describe occurrence of new HCV
      diagnosis during follow-up according to self-reported sexual behaviours and
      recreational drug use three months prior to questionnaire (Fisher's exact test).
      RESULTS: Cumulative HCV prevalence among MSM prior to ASTRA was 13.3% (95% CI
      11.5-15.4). Clinic- and age-adjusted prevalence ratios (95% CI) for cumulative
      HCV prevalence were 4.6 (3.1-6.7) for methamphetamine, 6.5 (3.5-12.1) for
      injection drugs, 2.3 (1.6-3.4) for gamma hydroxybutyrate (GHB), 1.6 (1.3-2.0) for
      nitrites, 1.7 (1.5-2.0) for all condom-less sex (CLS), 2.1 (1.7-2.5) for CLS-HIV
      seroconcordant, 1.3 (0.9-1.9) for CLS-HIV-serodiscordant, 2.0 (1.6-2.5) for group
      sex, 1.5 (1.2-1.9) for more than 10 new sexual partners in the past year. Among
      1,195 MSM with 2.2 years [IQR 1.5-2.4] median follow-up, there were 7 new HCV
      cases during 2,033 person-years at risk. Incidence was 3.5 per 1,000 person-years
      (95% CI 1.6-7.2). New HCV was recorded in 1.3% MSM who used methamphetamine
      versus 0.5% MSM who did not (p=0.385); 3.7% MSM who injected recreational drugs
      versus 0.5% MSM who did not (p=0.148); 2.9% MSM who used GHB versus 0.4% MSM who
      did not (p=0.003); 1.5% MSM who used nitrites versus 0.2% MSM who did not
      (p=0.019); 1.1% MSM having CLS versus 0.3% MSM who did not (p=0.084); 1.7% MSM
      having CLS-HIV-serodiscordant versus 0.4% MSM who did not (p=0.069); 0.9% MSM who
      had CLS-HIV-seroconcordant versus 0.5% MSM who did not (p=0.318); 0.8% MSM who
      had group sex versus 0.5% MSM who did not (p=0.463); and 1.6% MSM with =10 new
      sexual partners in the previous year versus 0.2% MSM with no or up to 9 new
      partners (p=0.015). CONCLUSIONS: Self-reported recent use of recreational and
      injection drugs, condom-less sex and multiple new sexual partners are associated
      with pre-existing HCV infection and, with the exception of injection drugs,
      appear to be predictive of new HCV co-infection among HIV-diagnosed MSM.

PMID- 25394135
TI  - Hepatic safety of RPV/FTC/TDF single tablet regimen in HIV/HCV-coinfected
      patients. Preliminary results of the hEPAtic Study.
AB  - INTRODUCTION: Although hepatotoxicity related to antiretroviral treatment (ART)
      has become less frequent, hepatotoxic events, such as transaminase elevations
      (TE), are still a matter of concern. RPV/FTC/TDF (EPA) is a new single tablet
      regimen which is widely used in real life practice. Clinical trials showed an
      adequate profile of liver safety in the sub-population of HIV/HCV-coinfected
      patients receiving rilpivirine. However, the number of individuals included in
      these analyses is low (1). The aim of this ongoing study is to evaluate the
      incidence of TE and total bilirubin elevations (TBE) during the first 48 weeks of
      EPA-based therapy in a large population of HIV/HCV-coinfected subjects outside of
      clinical trials. PATIENTS AND METHODS: This is a retrospective analysis of
      HIV/HCV-coinfected subjects who started EPA at the infectious diseases units of
      14 centres throughout Spain, included as cases. Subjects who started an ART
      different to EPA during the study period at the same hospitals were selected as
      controls. The primary outcome variables were grade 3 or 4 TE and grade 4 TBE.
      RESULTS: Of the 191 patients included, 31 (16.2%) subjects were naive to ART.
      Eighty-seven individuals started EPA and the remaining ones were controls. The
      most common NRTI backbone among the controls was TDF/FTC [59 (56.7%) patients]
      followed by NRTI-sparing regimens [24 (23.1%) individuals] and ABC/3TC [17
      (16.3%) subjects]. Among controls, 67 (64.4%) started a ritonavir-boosted
      protease inhibitor, mainly DRV/r [41 (39.4%) patients] followed by ATV/r [16
      (15.4%) subjects]. EFV, ETV and RAL were started in 16 (15.4%), 12 (11.5%) and 13
      (12.5%) subjects, respectively. The median (Q1-Q3) follow-up was 5.79 (3.65-8.61)
      months for the cases and 11.44 (5.8-12.88) months for the controls. TE was
      observed in two (2.3%) cases versus five (4.8%) controls (p=0.358), accounting
      for a density of incidence of 4.32/100 person-years versus 5.51/100 person-years
      [incidence rate difference (95% confidence interval): -1.88 (-9.95-6.2),
      p=0.354]. All TE were grade 3 and no patient discontinued ART due to TE. None of
      the cases developed TBE versus four (3.8%) controls, all of them receiving ATV/r.
      CONCLUSIONS: The frequency of grade 3-4 TE associated with EPA in HIV/HCV
      coinfected patients under real life conditions is very low. In addition, TE in
      HIV/HCV-coinfected patients treated with EPA are usually mild and do not lead to
      treatment discontinuation. TBE was not seen in patients taking EPA. All these
      data confirm that EPA is safe in this particular subpopulation.

PMID- 25394136
TI  - Hepatitis B virus (HBV) status of children born to HIV/HBV co-infected women in a
      French hospital: a cross-sectional study.
AB  - INTRODUCTION: Human Immunodeficiency Virus (HIV) Mother-To-Child-Transmission
      (MTCT) and prevention by combined antiretroviral therapy (cART) have been
      extensively studied. Hepatitis B Virus (HBV) MTCT from HIV/HBV co-infected women
      and prevention by antiretroviral therapy with dual activity have been poorly
      studied. The aim of the study was to assess HBV MTCT from HIV/HBV co-infected
      women in a developed country with a large access to cART. MATERIALS AND METHODS:
      HIV/HBV co-infected pregnant women attending the Obstetrics Department from 1st
      January 2000 to 1st January 2012 could be included in the study (NCT02044068).
      Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or
      vaccine to newborns was retrospectively recorded. We assessed HBV status of
      children at least as old as two years. RESULTS: Forty nine (9.2%) from 530 HIV
      infected women followed in the hospital were HIV/HBV co-infected. 34 (69.4%) had
      given birth to 57 children in the hospital. 13 of these women (22 children) were
      lost-to-follow-up, 21 women (35 children) could be studied. Twenty six children
      (74.3%) had HBs Ab at a protective level, 22 of them had received immunoglobulin
      at birth; 24 had received a complete vaccine schedule during the first six months
      of life (with immunoglobulin in 21 cases). The women had been given lamivudine or
      tenofovir/emtricitabine during eight and nine pregnancies respectively. Eight
      children (22.8%) were tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%)
      had received immunoglobulin and a complete vaccine schedule; in two children,
      immunoglobulin was uncertain; in one child, the vaccine schedule was incomplete;
      in the last one, data about immunoglobulin and the vaccine schedule were lacking.
      The women had been given lamivudine or tenofovir/emtricitabine during five and
      two pregnancies respectively. One child had HBc Ab and HBs Ab, immunoglobulin was
      uncertain and the vaccine schedule was incomplete. The woman had been given
      lamivudine during the last trimester. CONCLUSIONS: Three quarters of the children
      were protected. HBs Ab were negative in more than a tenth of the children who had
      received immunoglobulin and a complete vaccine schedule, questioning on long-term
      protection and underlining the need of control.

PMID- 25394137
TI  - Efficacy and tolerability of telaprevir (TVR)-based triple therapy in HIV/HCV
      coinfected patients.
AB  - INTRODUCTION: Clinical trials (CT) on triple therapy against HCV infection in HIV
      infected patients including TVR plus pegylated interferon and ribavirin (PR) have
      reported considerably higher response rates than with PR alone. This study was
      aimed to evaluate the efficacy and safety of triple therapy including TVR in
      HIV/HCV-coinfected patients in real-life conditions. MATERIALS AND METHODS:
      HIV/HCV genotype 1 patients seen at four Hospitals in Madrid who received therapy
      including TVR plus PR for at least two weeks were included. The response was
      evaluated during treatment, and sustained viral response (SVR) was evaluated 12
      and 24 weeks after the end of the treatment. RESULTS: Fifty-eight patients have
      been included; 79% male, median age 48 y.o.; 38% were IL28B rs12979860 genotype
      CT or TT, 58.6% of patients presented cirrhosis and 24.1% presented fibrosis F3.
      Infection with genotype 1a was observed in 53.4% of patients. Median baseline HCV
      RNA was 3,282,263 IU/mL (77.5% had >800,000 IU/mL). The most commonly used
      antiretroviral (ARV) drugs were tenofovir/emtricitabine [36 (62%) patients],
      etravirine [21 (36%) patients], abacavir/lamivudine [18 (31%) patients], boosted
      protease inhibitors [16 (27.5%) patients] and raltegravir [12 (20.6%) patients].
      Of the 42 (72.4%) patients who had received previous HCV treatment, 13.7% were
      null responders, 25.8% were partial responders and 31% had relapsed. In an ITT
      approach, proportions of patients with undetectable HCV RNA were 67.8% (38/56) at
      TW4, 83.3% (40/48) at TW12, 80% (36/45) at TW24, 79.4% at TW36 (31/39) and 72%
      (26/36) at TW48. Fifteen (25.8%) patients discontinued HCV therapy [8 (13.8%)
      because they fulfilled stopping rules, 5 (8.6%) individuals due to adverse events
      and 2 (3.4%) were lost to follow-up]. Rash associated with TVR (grade 1) was
      observed in two cases (3.4%) and all the patients showed anaemia at some point of
      treatment. In an analysis by ITT in the 31 patients who had a 60 week follow-up
      after starting therapy, SVR-12 was observed in 21 (67.7%) patients. And in the
      analysis by ITT in 28 patients who had a 72 week follow-up after starting
      therapy, SVR-24 was observed in 17 (60.7%) patients. CONCLUSIONS: Response to
      triple therapy with TVR plus PR in HIV/HCV-patients under real-life conditions,
      and therefore, including a high proportion of difficult to treat patients, is
      similar to that found in CT. The safety profile of TVR-based therapy is also
      comparable to that shown in CT, with only a rate of discontinuation of 8.6% of
      individuals related to toxicity.

PMID- 25394138
TI  - Telaprevir or boceprevir in HIV/HCV-1 co-infected patients in a real-life
      setting. Interim analysis (24 weeks). COINFECOVA-SEICV study.
AB  - INTRODUCTION: In general, HIV co-infected patients included in clinical trials
      evaluating the hepatitis C virus (HCV) therapy with telaprevir (TVR) or
      boceprevir (BOC) with advanced fibrosis, are scarce. We analyze data concerning
      the use of these drugs in a real-life clinical setting with patients affected by
      a more advanced degree of fibrosis in a Spanish cohort. METHODS: We evaluated
      safety and efficacy in an interim analysis encompassing the first 24 weeks of
      triple therapy with peginterferon (alfa-2a or alfa-2b), ribavirin and TVR or BOC
      in an observational, multicentre study. HIV/HCV genotype 1 co-infected patients
      beginning therapy from January 2012 to July 2013 were included. RESULTS: Enrolled
      patients were 155 (144 patients on TVR and 11 on BOC), average age was 47 years,
      83% were male. With respect to HCV treatment, 44% were naive, 13% relapsers, 17%
      partial responders, 21% null responders, and in seven patients, the previous
      response was unknown. All but three (98%) were under antiretroviral therapy (ART)
      (other than reverse transcriptase inhibitors, the backbone was raltegravir 43%,
      atazanavir 35%, and etravirine 28%). Median HCV-RNA at baseline was 6.1 log10,
      54% were cirrhotic and 38% F3. At week 4, 93% of patients continued on therapy,
      81% at w12, and 73% at w24. Virological failure was observed more frequently in:
      cirrhotic patients (19% [95% CI, 11-27]) vs F3 (12% [CI, 4-20]); patients with TT
      allele of the IL28B polymorphism (40% [CI, 18-61]) vs CT (21% [CI, 12-31]), or CC
      (2,2% [CI, -2-6]); previous null responders (37.5% [CI, 21-54]) vs partial
      responders (15.4% [CI, 1-29]), naive (13% [CI, 5-21]) or relapsers (0% [CI, 0
      0]); and in patients with a genotype subtype 1a (23.6% [CI, 57-76]) vs 1b (8.1%
      [CI, -1-17]). Overall, 17% had virological failure and in 8% treatment was
      discontinued due to adverse events. Severe adverse events occurred in 30 patients
      (19%). Haematologic disorders were the most common type including severe anaemia
      in 12 (7.7%) patients. Erythropoietin was employed in 41 patients (26.4%) and 11
      (7.1%) received blood transfusions. Nineteen patients (12.2%) were treated with G
      CSF, and 17 (11%) with thrombopoietin-receptor agonists. Five patients died
      (3.2%), three due to hepatic decompensation, one due to pneumonia and one due to
      pulmonary hypertension. CONCLUSIONS: In a real-life setting, therapy against HCV
      in co-infected patients with advanced liver fibrosis shows high virologic success
      at 24 weeks. However, frequent haematologic disorders are observed and a close
      monitoring and an intensive therapy are needed to optimize the results.

PMID- 25394139
TI  - Effect of HIV infection-related factors on SVR rate in HCV treatment in HIV
      infected patients.
AB  - INTRODUCTION: Factors that have an effect on the rate of sustained virological
      response (SVR) in chronic hepatitis C (CHC) patients include: genotype of
      hepatitis C virus (HCV); level of HCV RNA replication and rate of its reduction
      in the course of treatment; original hepatic fibrosis level; genotype of
      Interleukin-28B (especially for Genotype 1 HCV - G1); daily ribavirin (RBV) dose.
      This study evaluated the effect of the HIV infection-related factors on the SVR
      rate in HCV treatment in patients with concurrent infection (HIV/HCV). METHODS:
      The follow-up included 232 HIV/HCV-infected patients. Ninety-nine of 232 patients
      with HIV/HCV-infection received antiretroviral therapy (ART) for at least three
      months before the initiation of the CHC treatment. Before the HCV therapy, the
      median of CD4+cells was 406/mm(3) (with ART) and 507/mm(3) (without ART).
      Patients received HCV treatment with pegylated interferon (PEG-IFN) and RBV
      (1000/12,000 mg/day) during 24-48 weeks. RESULTS: SVR was received in 50% of
      patients with G1 HCV, and 80.1% of patients with Genotypes 2/3 (G2/3; p<0.0001).
      The SVR rate in the group of patients without ART was reliably higher, 74.4%
      (with ART - 58.6%; p=0.0053). No significant differences in the SVR rate (62.3%
      and 69.6%, accordingly) were detected after the differentiation of patients based
      on the initial absolute values of CD4+cells count (<350 cells/mm(3) and >350
      cells/mm(3)). In 127 patients with the HIV/HCV-infection, the percentage of
      CD4+cells before the CHC treatment was >25% and more (Group 1 [Gr. 1]), and in
      105 patients <=25% (Group 2 [Gr. 2]). The SVR rate for Gr. 1 patient was 74.6%,
      and for Gr. 2 patients -58.1% (p=0.0023). The SVR rate in patients with G1 HCV
      was 56.8% (Gr. 1) and 44.2% (Gr. 2; p=0.1095), whereas the rate for G2 and 3 was
      85.5% and 71.7%, accordingly (p=0.0242). Forty patients in Gr. 1 and 59 patients
      in Gr. 2 received ART. The comparison of the SVR rate for these patients showed
      no significant differences: 60% and 57.6%, accordingly. SVR rate in the patients
      without ART demonstrated that for Gr.1 patients (CD4+>25%) was reliably higher,
      82.8% (compared to Gr.2 with 58.7%; p=0.0012). CONCLUSIONS: Along with factors
      related to HCV and the patient, the SVR rate in the HCV treatment with PEG-IFN
      and RBV may be affected in patients with the concurrent infection by the use of
      ART and original relative content of CD4+cells. The maximum SVR rate was achieved
      in the patients without ART and with the CD4+cells >25% (baseline). When
      indicted, it is reasonable to provide HCV treatment to HIV-infected patients as
      long as the percentage of CD4+cells remains high and there is no need of ART.

PMID- 25394140
TI  - Liver Fibrosis progression using Fibroscan in HIV/HCV coinfected patients with
      undetectable HIV viral load.
AB  - INTRODUCTION: Several factors such as duration of infection, age, male gender,
      consumption of alcohol, HIV infection and low CD4 count have been associated with
      fibrosis progression rate. However, it is relatively scarce, the knowledge about
      the liver fibrosis progression rate in HIV-infected patients with undetectable
      HIV viral load (VL). For this reason, we performed the present study. MATERIALS
      AND METHODS: Observational and multicenter study (2008-2012) conducted in four
      hospitals of the northern Spain. HIV/HCV (hepatitis c) virus coinfected patients
      >=18 years on stable combination antiretroviral therapy (cART) (>=6 months) and
      with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis
      progression. Fibrosis progression was assessed using a Fibroscan(r) (502 STEP 3
      model) and measuring a basal test and a second one at least 12 months apart from
      baseline. This evolution was compared with different variables such as duration
      of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype,
      CD4 lymphocyte counts and the cART employed at the basal test. RESULTS: A total
      of 608 patients were included (median age 29.4 years, 71.7% men). Of these, 463
      patients met the inclusion criteria. In these patients, the liver fibrosis
      progression was nearly flat and the only variables related to a higher liver
      fibrosis progression were the increasing age of the patients (p=0.02) and the
      duration of the coinfection (p=0.001). CD4 lymphocyte counts showed a tendency to
      improved liver fibrosis (p=0.056). CONCLUSIONS: In HIV/HCV coinfected patients on
      stable cART and HIV undetectable VL, the increase in liver fibrosis rate
      progression was nearly flat, although it was significantly associated with the
      duration of the coinfection and the age of the patient. The beneficial effects of
      the cART were independent of the antiretroviral drug employed. A tendency to a
      lower fibrosis progression was observed in those patients with a higher CD4
      count.

PMID- 25394141
TI  - Evaluation of the degree of liver fibrosis and genetical characteristics in HIV
      patients with spontaneous clearance of HCV in Cartagena, Spain.
AB  - INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in the region of the
      Interleukin 28B (IL28B) gene on chromosome 19, coding for the interferon (IFN)
      lambda3, are involved in hepatitis c virus (HCV), spontaneous clearance. There is
      little information on the degree of liver fibrosis (LF) in HIV patients, who have
      had spontaneous clearance of HCV. Our objective in this study is to assess the
      degree of liver fibrosis in this population, as well as to identify key genetic
      characteristics associated with spontaneous clearance. MATERIALS AND METHODS:
      Retrospective descriptive study that evaluated from 1 January 2013 to 30 May
      2014, the HIV-HCV coinfected patients in which it has been demonstrated
      spontaneous clearance of HCV infection. The main variables analyzed were (1)
      genetics: Haplotype determination of genetic polymorphism SNP rs12979860 in the
      region of IL 28B gene and (2) grade of LF measured in kilopascals (kPa) by
      transient elastography (TE). RESULTS: We evaluated 205 patients with HIV and HCV
      coinfection, of whom, 17 patients (8.3%), presented spontaneous clearance.
      Fourteen patients (82.4%) had HIV CV<20 copies/mL, while the mean CD4 cell count
      was 396 (SD: 245) cells/mcL. Nine (53%) patients were analyzed for SNP rs12979860
      of IL 28B gene. Nine patients (100%) had the CC haplotypes, and no cases of CT
      and TT haplotypes were detected (p<0.001). LF was measured by TE in 12 (70.6%)
      patients. The median of LF (Kpa) was 5.95 (IQR 4.78). In four patients (33.3%)
      were observed significant LF (F3-F4). In the univariate analysis, no significant
      differences in the median of LF (Kpa) of HIV patients with spontaneous clearance
      of HCV were observed with respect to the coinfected HIV-HCV patients with SVR to
      antiviral therapy (N=34; median 9.6 Kpa; IQR: 10.7; p=0.92) or the coinfected HIV
      HCV group who did not receive antiviral therapy (N=124; median 8.5 kPa; IQR:
      7.65; p=0.85). CONCLUSIONS: Spontaneous clearance of HCV in our series of
      patients coinfected with HIV infection represents an uncommon clinical
      phenomenon. The immune status was preserved and most patients had HIV virological
      suppression. In all patients in which the IL 28B genetic polymorphism was
      determined, CC haplotypes were found. The degree of LF (Kpa) in this population
      was low (<9.5 Kpa) and a low proportion of subjects showed significant LF (F3
      F4). No differences in the degree of LF were found in this group compared to
      coinfected patients receiving HCV treatment with SVR and compared to untreated
      patients coinfected with HIV-HCV.

PMID- 25394142
TI  - Acute hepatitis C virus (HCV) infection in the setting of HIV coinfection: a
      single-centre 10-year follow-up.
AB  - INTRODUCTION: Acute hepatitis C virus (HCV) infection has emerged as a major
      cause of morbidity in the HIV-infected population. Most guidelines recommend
      early treatment with pegylated interferon and ribavirin due to higher cure rates.
      The impact of acute HCV and its treatment on the outcome of the HIV-infected
      population is unknown. With new treatment options for HCV, early treatment of
      acute HCV has to be questioned. Here, we report a long-term analysis on patients
      with acute HCV. METHODS: Retrospective analysis from an outpatient clinic from
      Berlin. All patients with the diagnosis of acute HCV according to The European
      AIDS Treatment Network (NEAT) criteria were included in the database at their
      date of HCV diagnosis and followed-up until the last medical contact. Demographic
      data was taken from the medical file. A fibrosis estimation was performed using
      transient elastography (Fibroscan((r)). A Fibroscan value above 7 kPa was
      considered as significant fibrosis, above 12.4 kPa as liver cirrhosis. The
      following outcomes were documented: (a) liver-related: hepatic decompensation,
      cirrhosis, hepatocellular carcinoma. (b) non-liver-related: death, myocardial
      infarction, AIDS-defining event, psychiatric hospitalisation. RESULTS: A total of
      207 cases of acute HCV infection in HIV-infected patients were diagnosed between
      May 2002 and September 2013. All patients were male and declared homosexual
      contacts as their risk factor for having acquired HIV. The mean age was 39 years,
      162 patients (78%) were on antiretroviral treatment, and the median CD4 cell
      count was 593/mm(3) (IQR 443-749). At HCV diagnosis, the highest median alanine
      aminotransferase (ALT) level was 408 IU/mL (159-871), the HCV viral load was
      800,000 IU/mL (45x103-2.8x106). 22 cases (11%) cleared their infection
      spontaneously, 161 (77%) underwent interferon-based treatment. Of those treated,
      58% had a sustained virological response. 36 cases of HCV reinfection were
      documented. All patients were followed-up over an interval of 806 patient-years.
      The median liver stiffness was 5.3 kPa (4-7) after a median interval of 34
      months. 33 patients developed significant fibrosis, and 11 patients (6%)
      developed cirrhosis. Nine (5%) patients died during follow-up, and 11 developed
      non-liver-related endpoints. All but one deceased patients had interferon-based
      treatment. CONCLUSIONS: Severe hepatic disease and death rarely occurs in a
      highly treated HCV population. As interferon-based treatment may induce side
      effects, it is from now on justified to await new HCV treatment options.

PMID- 25394143
TI  - Experience of acute hepatitis C and HIV co-infection in an inner city clinic in
      the UK.
AB  - INTRODUCTION: Acute hepatitis C infection (HCV) is increasing in the HIV-infected
      population, particularly among men who have sex with men (MSM). Patients co
      infected with HCV and HIV progress more rapidly to liver cirrhosis and are at
      higher risk of hepatocellular carcinoma. We looked at our management of acute HCV
      to assess treatment outcome. MATERIALS AND METHODS: We performed a retrospective
      and prospective case note review of HIV-HCV co-infected patients attending a
      large inner city sexual health clinic from 2006-to date. Acute HCV infections
      (less than six months) were identified and data was collected on demographics,
      transmission and treatment outcomes. Treatment regime was 48 weeks of weight
      based ribavirin and pegylated interferon alpha2a. RESULTS: Sixty-seven acute HCV
      infections were identified among 142 co-infected patients, all of whom were male
      and 66 (98.5%) were MSM. Median age at diagnosis was 37 (range 20-59) and 58
      (86.6%) were White British. Sixty patients (89.6%) were genotype 1, 3 (4.5%) were
      genotype 4 and 2 (3.0%) were genotype 2/3. A further 2 (3.0%) were re-infections.
      A peak in new HCV diagnoses was seen in 2013 with 17 (25.4%). Route of
      transmission was sexual in all cases with 13 (19.4%) also injecting drugs,
      pointing to mixed transmission routes. Nine (69.2%) of these occurred in 2013.
      Nine (13.4%) patients cleared HCV themselves. Of the 58 who didn't clear HCV, 12
      (20.7%) were lost to follow up/transferred care, 4 (6.9%) declined treatment
      awaiting newer agents, and 10 (17.2%) are waiting to start. A total of 32
      patients started treatment. Six (18.8%) patients are currently on treatment and
      three (9.4%) await a final sustained virological response (SVR) test. Six out of
      twenty-four (25.0%) stopped treatment due to lack of response and 1 stopped due
      to side effects. Fifteen (62.5%) achieved SVR and 2 (8.3%) failed to achieve SVR.
      Eight out of ten (80.0%) patients who had an early virological response (EVR)
      achieved SVR. CONCLUSIONS: Our data shows good treatment outcomes for acute HCV
      infection in HIV patients with an SVR rate of 62.5%. We've seen a steady increase
      in acute HCV infection, particularly in MSM injecting party drugs. Changing risk
      behaviours, particularly a rise in chem sex parties and club drug use, along with
      more anonymous partners and disclosure issues create difficulties in managing the
      HCV epidemic. More education is needed to raise awareness of HCV transmission and
      disclosure in our MSM population.

PMID- 25394144
TI  - Incidence of recent HCV infection among persons seeking voluntary counselling and
      testing for HIV and sexually transmitted infections in Taiwan.
AB  - INTRODUCTION: The incidence of recent hepatitis C virus infection (HCV) infection
      has been noted to be increasing among men who have sex with men (MSM), especially
      those with HIV infection, in several resource-rich settings. In Taiwan, the
      incidence of recent HCV infection increased from 0 in 1994-2000, 2.29 in 2001
      2005 to 10.13 per 1000 person-years of follow-up (PYFU) in 2006-2010. In this
      study, we aimed to estimate the incidence rate of recent HCV infection among
      those individuals who sought voluntary counselling and testing (VCT) service at a
      University Hospital. METHODS: Between May 2006 and December 2013, 18,246 tests
      for HIV antibody were performed among 12,143 individuals at the VCT services. A
      total of 2157 clients without HIV or HCV infection at baseline were included for
      estimation of incidence rate of recent HCV infection. Antibodies to HCV were
      determined with a third-generation enzyme immunoassay. A nested case-control
      study with four matched controls without HCV seroconversion for one HCV
      seroconverter was conducted to investigate the factors associated with recent HCV
      infection. Phylogenetic analysis was performed among the HCV strains obtained
      from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013.
      RESULTS: During the study period, 2157 clients received a total of 8260 tests.
      The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV-negative clients who
      contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35
      per 1000 PYFU; 95% CI, 1.76-4.94); the rate increased from 2.28 per 1000 PYFU
      (95% CI, 0.05-4.51) in 2006-2009, to 3.33 per 1000 PYFU (95% CI, 0.86-5.80) in
      2010-2011, to 4.94 per 1000 PYFU (95% CI, 0.99-8.99) in 2012-2013. In case
      control study, HCV seroconverters were more likely to have HIV-infected partners,
      recent syphilis and a Rapid Plasma Reagin (RPR) titre of 4 or greater. In
      multivariate analysis, having HIV-infected partners remained as the only
      independent associated factors with HCV seroconversion (AOR, 6.931; 95% CI, 1.064
      45.163). Phylogenetic analysis revealed transmission pairs and clusters, with
      most clustered sequences derived from MSM. CONCLUSIONS: Similar to the
      observation among HIV-infected patients who are not IDUs, increasing trends of
      recent HCV infection also occur among the individuals who sought VCT services in
      Taiwan. Having HIV-infected partners is independently associated with recent HCV
      seroconversion.

PMID- 25394145
TI  - Risk of liver decompensation assessed in HIV/HCV co-infected individuals with
      advanced liver fibrosis: a faster countdown experience.
AB  - INTRODUCTION: Cirrhosis secondary to HCV infection is expected to peak in the
      next decade, particularly in the HIV co-infected subgroup and has become a
      leading cause of morbidity among these individuals. Efforts must be done to
      estimate the risk of liver decompensation (LD) in the short term, in order to
      define the appropriate time for HCV treatment. MATERIALS AND METHODS:
      Retrospective observational cohort study aimed to assess the risk of LD among a
      group of HIV/HCV co-infected patients diagnosed in the past 23 years in a central
      hospital of Lisbon. INCLUSION CRITERIA: (1) advanced liver fibrosis >=F3; (2) HCV
      treatment naive or without sustained virologic response (SVR). Patients had a one
      to five years period of follow-up. Multiple linear regression, Mann-Whitney and
      Kendall were the statistical tests performed. RESULTS: From 444 HIV/HCV co
      infections, 66 met the inclusion criteria, with preponderance of male gender
      (82%), 35-45 years of age (55%), genotype 1a (52%), a mean of 13 years of co
      infection and an AIDS stage documented in 65%, though the majority is under
      antiretroviral therapy (86%) and have TCD4+>500 u/L (59%). Half (52%) showed
      evidence of steatosis, many of these (41%) presenting a history of alcoholism or
      overweight (BMI >=25 Kg/m(2)). Pre-cirrhotic (F3 or F3/4) or cirrhotic (F4) stage
      was documented in 36 and 30 patients respectively. After staging, 28 (42%)
      initiated HCV treatment and SVR was achieved in 8 (29%) of those. Five (14%) pre
      cirrhotic and twelve (40%) cirrhotic patients experienced at least one LD
      episode: 8 vs 28 cumulative events at five years and 2.8 vs 1.8 average years up
      to the first LD episode for pre-cirrhotic vs cirrhotic. The probability of
      remaining free of LD for pre-cirrhotic vs cirrhotic patients was 97% vs 78%
      (p<=0.01) at one year; 88% vs 65% (p<=0.001) at three years and 71% vs 44%
      (p<=0.001) at five years. Positive correlation was found between LD and the
      cirrhotic stage (vs pre-cirrhosis, p<=0.001), baseline AST >=100 u/L (vs <100
      u/L, p<=0.01) and platelet count <120 x 109/L (vs >120 x 109/L, p<=0.05).
      CONCLUSIONS: Cirrhosis accounts for a significant superior risk of LD. The time
      up to the first LD event differed in only one year between pre-cirrhotic and
      cirrhotic, standing for the importance of a rapid treatment referral in both
      subgroups. Modifiable risk factors that accelerate fibrosis are prevalent in
      HIV/HCV co-infected patients. Low platelet count, elevated AST and F4 stage
      predict the rapid progression to LD and the need for early HCV treatment. Large
      studies are required for further support of these results.

PMID- 25394146
TI  - Plasmacytoid Dendritic cells (pDCs) in HIV-infected and HIV/HCV-co-infected
      patients receiving successful treatment.
AB  - INTRODUCTION: Depletion of cellular pool and constant activation of plasmacytoid
      dendritic cells (pDCs) in HIV-infected persons (HIV+) are associated with disease
      progression and manifestation of opportunistic infections. The influence of
      highly-active antiretroviral treatment (HAART) and suppressed HCV-co-infection
      (HIV+/HCV+) on the extent of these changes remains unknown. OBJECTIVE: To study
      parameters of pDCs in peripheral blood of HIV+ and HIV+/HCV+ patients on HAART.
      METHODS: Twelve uninfected with HIV or HCV volunteers and 37 patients (12 HIV+, 9
      HIV+/HCV+ and 16 HCV+) were enrolled. All HIV+ patients received HAART and had
      undetermined HIV viral load. All HCV+ patients had finished antiviral therapy
      (Pegasys/ribavirin) with sustained viral response for six months and more. The
      pDC population was enumerated by flow cytometry. In vitro IFN production in the
      whole blood in response to pDC-specific stimulus unmethylated CpG
      oligonucleotides was determined by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The percentage of pDCs of peripheral blood mononuclear cells (PBMC) in
      HIV+/HCV+ was the lowest (0.08+/-0.02) but statistically not different from HIV+
      (0.15+/-0.03; p=0.11) and significantly lower than HCV+ (0.17+/-0.015; p=0.4) and
      controls (0.27+/-0.045; p=0.03). Absolute number of pDCs in HIV+ on HAART (6.3+/
      1.3) was not significantly lower than the control (10.25+/-1.75; p=0.09) but in
      HIV+/HCV+ (5.1+/-1.2; p=0.03), the difference was valid. IFN-alpha production by
      pDCs in patients on HAART in HIV+ (2.4+/-0.9 pg/ul) and in HIV+/HCV+ (3.7+/-1
      pg/ul) patients were significantly higher than in controls (in controls IFN-alpha
      production by pDCs in the native plasma was below the level of detection (3
      pg/ul), p=0.02 and p=0.0014). CONCLUSIONS: Absolute number of pDC in HIV-positive
      person on HAART with sustained viral response to treatment of HCV-co-infection
      was lower than in HIV-mono-infected. IFN-alpha production by pDC in HIV+ and in
      HIV+/HCV+ patients receiving HAART remains higher than in uninfected persons.

PMID- 25394147
TI  - The effects of Maraviroc on liver fibrosis in HIV/HCV co-infected patients.
AB  - INTRODUCTION: The fibrogenesis analysis in quimeric CCR1 and CCR5 mice revealed
      that CCR5 mediates its pro-fibrogenic effects in hepatic cells and promoting
      stellate cells. The blockage of co-receptors could preserve the progression of
      hepatic fibrosis in HIV/HCV co-infected patients. OBJECTIVE: To evaluate the
      beneficial effects on hepatic fibrosis in HIV/HCV co-infected patients that are
      on antiretroviral therapy (ART) with CCR5 co-receptor antagonists. METHOD AND
      MATERIALS: A multicentre, retrospective pilot study of the evaluation of hepatic
      fibrosis at mid- and long-term by non-invasive methods in a HIV/HCV co-infected
      patients cohort in the Valencian Community (Spain) that received ART with a CCR5
      co-receptor antagonist. The cut-off points of serum marker tests of hepatic
      fibrosis were: AST to Platelet Ratio Index (APRI)<0.5 (F0-F1); >1.5 F2; >2
      Cirrhosis and Forns Index<4.2 excludes fibrosis; >6.9>F2 fibrosis. Inclusion
      criteria was established for HIV/HCV co-infected patients on ART with CCR5 co
      receptor antagonists that had no previous history of interferon and ribavirin
      treatment or those who were null-responders and received CCR5 co-receptor
      antagonist treatment in the previous year. Patients with HBV infection were
      excluded. RESULTS: A total of 71 male patients (69%) were reported. A CD4 nadir
      <100 cells/uL was observed in 42% of patients and 62% (44/71) had a basal CD4
      level >350 cells/uL. According to genotypes, 50% were G-1a, 14% G-1b, 11% G-3 and
      25% G-4. The median duration of treatment with Maraviroc (MVC) was the following:
      45% took it over a year, 41% over two years and 14% over three years. Before
      starting treatment with MVC, we observed an initial fibrosis of F0-F1 in 49% of
      patients, F2-F3 in 24% and F4 in 27%. The medium follow-up was of 18.45 months.
      Progression to a higher fibrosis level was observed in five patients, 11 patients
      improved at least one stage and the others were stable over time. There were 38
      patients taking MVC over two years, 27 patients in this group (59.38%) did not
      modify their fibrosis, 3 patients (11%) progressed and 8 (29.62%) showed
      regression of liver fibrosis in one stage. CONCLUSIONS: The data above shows a
      benefit over fibrosis progression with MVC, expressed by fibrosis serum marker
      tests in HIV/HCV co-infected patients with CCR5 tropism. The prolong treatment
      with MVC (over two years) has a better effect on liver fibrosis.

PMID- 25394148
TI  - Safety analysis of raltegravir/truvada regimen in HIV/HCV co-infected patients
      without switchback after HCV treatment.
AB  - INTRODUCTION: Due to drug-drug interactions of HIV- and HCV-specific antivirals
      when initiating an HCV-therapy, the antiretroviral therapy (ART) often has to be
      changed. The spectrum of applicable antiretrovirals is small, therefore many
      patients were switched to raltegravir/truvada (RAL/TVD) in our cohort. Due to the
      relatively low genetic barrier of RAL, this regimen may be endangered to fail, if
      the NRTI backbone is not fully active because of pre-existing NRTI resistance. We
      investigated the long-term follow-up and safety of RAL/TVD in co-infected
      patients after hepatitis C virus (HCV) therapy was stopped and the protective
      antiretroviral effect of interferon ended. MATERIALS AND METHODS: Twenty patients
      initiated a direct-acting antiviral (DAA) containing HCV therapy (8x faldaprevir,
      6x telaprevir, 2x daclatasvir and 4x simeprevir) between 11/2011 and 01/2013.
      Seventeen were switched to RAL/TVD, three patients were not treated before, but
      started with the regimen. Diagnosis of HIV infection was dated between 1985 and
      2010. The HI-viral suppression was monitored retrospectively to date. RESULTS:
      Thirteen of the twenty patients (65%) remained on RAL/TVD after finishing HCV
      treatment, for seven patients, no data about their ART continuation was
      available, after HCV therapy had stopped. All remaining thirteen patients showed
      an HI-viral load below detection limit up to date (for 15 to 22 months, median 20
      months). Only for four patients, historic resistance data were available but none
      showed NRTI mutations. CONCLUSIONS: Switch to RAL/TVD as HIV ART due to
      initiating HCV therapy was safe for the observed small cohort even in long-term
      follow-up without switchback or a second ART switch. However, resistance data for
      the cohort was little, showing no NRTI mutations, indicating a relatively safe
      setting. Since no further data is available, physicians should keep in mind ART
      history, historical therapy failure and HIV-resistance while switching ART to
      treat HCV in co-infected patients. Further investigation in larger cohorts is
      needed, especially thinking of upcoming interferon-free HCV regimen in heavily
      pre-treated co-infected patients.

PMID- 25394149
TI  - Analysis of hepatitis non-treatment causes in a cohort of HCV and HCV/HIV
      infected patients.
AB  - INTRODUCTION: The decision to start hepatitis C virus (HCV) treatment and its
      timing remains controversial. As new treatment regimens are approved, it is
      essential to identify patients eligible for each regimen in a timed and tailored
      approach. This study aims to identify the reasons to defer treatment of chronic
      hepatitis C infection in both HCV and HCV/HIV infected patients. MATERIALS AND
      METHODS: Retrospective observational study of a cohort of HCV chronically
      infected patients with or without HIV infection, followed in an infectious
      disease clinic in Lisbon. Demographic, epidemiological, clinical, immunologic and
      virologic data were collected. Statistical analysis was performed with Microsoft
      Office((r))- Excel 2012. Kolmogorov-Smirnov, t-test, Chi-square and correlation
      analysis were performed for a significant p value<0.05. RESULTS: The study
      included 669 patients, 225 patients infected with HCV (group A) and 444 patients
      co-infected with HCV/HIV (group B). The comparative analysis of those groups (A
      vs. B) showed: mean age was 49.4 years versus 46.9 (p<0.01), mean time since HCV
      diagnosis was 9.5 versus 14.6 years (p=0.558) both groups shared a male
      predominance and HCV acquisition due to intravenous drug use. Regarding genotype
      characterization, the predominant was 1a in both groups (p<0.01). Evaluation of
      IL28B polymorphism revealed CC 15.5% (A) versus 9.45% (B) (p<0.01). Group B mean
      TCD4 count was 585 cells/uL (mean percentage 27.1%). There was spontaneous viral
      clearance in 10.7% (A) versus 4.1% (B) (p<0.01). There were treated 52.0% (A)
      versus 32.2% (B) patients (p<0.01). For the untreated ones (107 - group A vs 270 
      group B), no reason was identified for treatment deferral in 32.5% (A) versus
      48.0% (B) patients. The most frequent reasons for deferring treatment were:
      withdrawal to follow-up (33.7%), active staging of disease (7.2%), alcohol abuse
      (6.0%) and advanced age (6.0%) in group A versus low TCD4 cell count (17.1%),
      loss to follow-up (7.5%), poor adherence (7.5%) and alcohol abuse (3.2%) in group
      B. CONCLUSIONS: One of the highlighted cause for treatment deferral in both mono
      and co-infected patients was withdrawal to follow-up. In co-infected patients,
      low TCD4 cell count and poor adherence, also gain prominence, suggesting that
      strategies to improve retention in care may be needed. Additionally, emergence of
      direct-acting antiviral agents is expected to reduce these determinants in
      starting treatment, namely reduce the impact of low TCD4 count in co-infected
      patients.

PMID- 25394150
TI  - Incidence of cervical dysplasia and cervical cancer in women living with HIV in
      Denmark: comparison with the general population.
AB  - INTRODUCTION: Women living with HIV (WLWH) are reportedly at increased risk of
      invasive cervical cancer (ICC). WLWH in Denmark attend the National ICC screening
      program less often than women in the general population. We aimed to estimate the
      incidence of cervical dysplasia and ICC in WLWH in Denmark. METHODS: We studied a
      nationwide cohort of WLWH and a cohort of age-matched females from the general
      population in the period 1999-2010. Pathology samples were obtained from The
      Danish Pathology Data Bank containing nationwide records of all pathology
      specimens. The cumulative incidence and hazard ratios (HRs) for time from
      inclusion to first cervical intraepithelial neoplasia (CIN)/ICC and time from
      first normal cervical cytology to first CIN/ICC were estimated. Sensitivity
      analyses were performed to include prior screening outcome, screening intensity
      and treatment of CIN/ICC in the interpretation of results. RESULTS: We followed
      1,143 WLWH and 17,145 controls with no prior history of ICC for 9,509 and 157,362
      person-years. Compared to controls, the overall incidence of CIN1 or worse
      (CIN1+), CIN2+ and CIN3+ was higher in WLWH and predicted by young age and CD4
      count <200 cells/uL. In women with normal baseline cytology, incidences of CIN1+
      and CIN2+ were higher in WLWH. However, incidences were comparable between WLWH
      and controls adherent to the National ICC screening program. CONCLUSIONS:
      Overall, WLWH develop more cervical disease than controls. However, incidences of
      CIN are comparable amongst WLWH and controls adherent to the National ICC
      screening program and with a normal baseline cytology.

PMID- 25394151
TI  - Bladder cancer in HIV-infected adults: an emerging concern?
AB  - INTRODUCTION: As HIV-infected patients get older more non-AIDS-related
      malignancies are to be seen. Cancer now represents almost one third of all causes
      of deaths among HIV-infected patients (1). Albeit bladder cancer is one of the
      most common malignancy worldwide (2), only 13 cases of bladder cancer in HIV
      infected patients have been reported in the literature so far (3). MATERIALS AND
      METHODS: We conducted a monocentric study in our hospital. We selected all
      patients who were previously admitted (from 1998 to 2013) in our hospital with
      diagnoses of HIV and bladder cancer. The objective was to assess the prevalence
      and characteristics of bladder cancers in HIV-infected patients in our hospital.
      RESULTS: Based on our administrative HIV database (6353 patients), we found 15
      patients (0.2%) with a bladder cancer. Patients' characteristics are presented in
      Table 1. Patients were mostly men and heavy smokers. Their median nadir CD4 cell
      count was below 200 and most had a diagnosis of AIDS. A median time of 14 years
      was observed in those patients, between the diagnosis of HIV-infection and the
      occurrence of bladder cancer, although in patients much younger (median age 56)
      than those developing bladder cancer without HIV infection (71.1 years) (4).
      Haematuria was the most frequent diagnosis circumstance in HIV-infected patients
      who had relatively preserved immune function on highly active antiretroviral
      therapy (HAART). Histopathology showed relatively advanced cancers at diagnosis
      with a high percentage of non transitional cell carcinoma (TCC) tumor and of TCC
      with squamous differentiation, suggesting a potential role for human papilloma
      virus (HPV) co-infection. Death rate was high in this population. CONCLUSIONS:
      Bladder cancers in HIV-infected patients remain rare but occur in relatively
      young HIV-infected patients with a low CD4 nadir, presenting with haematuria,
      most of them being smokers, and have aggressive pathological features that are
      associated with severe outcomes.

PMID- 25394152
TI  - Autologous stem cell transplantation in HIV-related lymphoma in the rituximab era
      - a feasibility study in a monocentric cohort.
AB  - INTRODUCTION: Since the introduction of highly active antiretroviral therapy
      (HAART) (1) and later on the availability of anti-CD20 monoclonal antibody
      treatment (2), the therapeutic options as well as the prognosis of AIDS related
      lymphoma (ARL) have been improved. There is however no uniform agreement on how
      to treat patients who do not achieve a partial remission, who experience a
      relapse or who have very aggressive subtypes. Autologous hematopoietic stem cell
      transplantation (ASCT) has become an option for those patients. We
      retrospectively examined ARL patients to elucidate the feasibility of high-dose
      chemotherapy and autologous stem cell transplantation. PATIENTS AND METHODS: Data
      of seven male and one female HIV+ patients with ARL was collected and informed
      consent was obtained. Age, HIV disease characteristics (CD4 count, HIV-RNA-PCR,
      ART) and transplantation-related details (histopathology, myeloablative therapy,
      neutrophil engraftment and NCI-CTCAE during/after transplantation as well as
      follow up and survival) were obtained from the patients' medical records.
      RESULTS: Eight patients were treated with the intent of ASCT. The median age was
      at 64 years. Four patients had experienced prior AIDS. The median CD4 NADIR was
      at 157/ul, the median CD4 count at diagnosis of lymphoma at 81/ul. Five patients
      were receiving combination antiretroviral therapy (cART) at the time of lymphoma
      diagnosis, four of which had achieved a viral load of less than 50/ul. Two
      patients have died, due to (Nr. 8) a transplant-related complication (non
      infectious leukoencephalophathy). The other patient died of an unknown reason
      (351 days after transplantation). The median survival is at 345 days to date. The
      time until engraftment was well at 11 days. Grade 3/4 haematological toxicity was
      present in all patients. Five out of three patients developed infectious
      complications, but there were no infection-related deaths. One patients (Nr. 4)
      developed a Kaposi Sarcoma reactivation that necessitated further chemotherapy.
      CONCLUSIONS: ASCT is feasible in high risk ARL with good engraftment. Toxicity
      was substantial and studies are needed to define which patients have an unduly
      high risk of toxicity.

PMID- 25394153
TI  - Prevalence of monoclonal gammopathy in HIV patients in 2014.
AB  - INTRODUCTION: In non-HIV patients, Monoclonal Gammopathy of Undetermined
      Significance (MGUS) is associated with an increased risk of subsequent
      development of haematologic malignancies, especially multiple myeloma (MM) and it
      has been recently demonstrated that MM is always preceded by a MGUS phase. A
      higher prevalence of MGUS and MM has been observed in HIV patients compared to
      the general population. Nevertheless, it has been shown that MGUS in the context
      of HIV can disappear with antiretroviral therapy (ART). So, measuring MGUS
      prevalence in HIV patients in the recent period appears of special interest.
      MATERIALS AND METHODS: From January to June 2014, in each out-patient seen in our
      unit, a serum protein electrophoresis was performed. RESULTS: A total of 393
      patients were screened. Eight patients with HIV2 and one patient with HIV1+HIV2
      infection were excluded. Finally, 383 patients (173 female, 210 male) with HIV1
      infection were analyzed. Characteristics of patients were as follows: median age
      42.2 years (19.1-79.1), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co
      infection 47 (18.8%), median CD4 610 (2-1758), CD8 793 (113-4010), presence of a
      past AIDS event for 88 patients (23%). Median time with HIV infection was 11
      years (0-30). Three hundred fifty-nine patients (93.7%) were on ART for a median
      duration of 105 months (0-287). For 320 patients (83.6%), viral load was below 50
      viral copies/ml. Twelve cases of MGUS (3.1%) were observed: IgG Kappa (five
      cases), IgG Lambda (five cases), biclonal with two IgG Kappa (one case) and in
      one case, three monoclonal immunoglobulins were observed (IgG Kappa*2+IgG
      Lambda). The monoclonal immunoglobulin's level was low and below 1 g/l in all
      cases except two (2.1 and 11.6 g/l). No factor was found to be predictive of the
      presence of MGUS in particular age, CD4, HBV/HCV co-infection, viral load or ART.
      CONCLUSIONS: In the context of modern ART, the prevalence of MGUS remains above
      those observed in the general population. Even if the level of monoclonal spike
      observed in our cohort is generally low, an excess risk of subsequent development
      of MM could be present. Nevertheless, a prospective follow-up of HIV patients
      with MGUS is necessary to determine this risk.

PMID- 25394154
TI  - Haemophagocytic syndrome and elevated EBV load as initial manifestation of
      Hodgkin lymphoma in a HIV patient: case report and review of the literature.
AB  - INTRODUCTION: In HIV patients, haemophagocytic syndrome (HPS) may occur in the
      presence of cancer, concomitant viral infection, HIV primo-infection or at the
      initiation of highly active antiretroviral therapy (HAART). Hodgkin lymphoma
      remains a rare cause of HPS. We describe a case of HPS with very high Epstein
      Barr virus (EBV) load in a HIV patient as initial manifestation of Hodgkin
      lymphoma. MATERIALS AND METHODS: A 29-year-old HIV positive man, successfully
      treated with HAART with an undetectable viral load and CD4 cells count of 438/ul,
      was admitted for high fever of unknown origin. Laboratory results showed a
      pancytopenia with haemoglobin at 82 g/l, lymphocyte count at 0.36G/l and
      platelets count at 47G/l; a highly elevated ferritine >7500 ug/l; increased
      lactate dehydrogenase at 885U/l and soluble IL2 receptor (CD25) >60 ng/ml. EBV
      load was measured and confirmed at 2,600,000 copies/ml. A PET-CT imaging showed
      diffuse elevated metabolic activity in the bone marrow and in two lesions in the
      spleen without lymphadenopathy. Bone marrow and liver biopsies revealed images of
      haemophagocytosis and lymphocyte depleted Hodgkin lymphoma. Treatment consisted
      in etoposid, steroids, and R-ABVD (rituximab, doxorubicin, bleomycin,
      vinblastine, dacarbazine) chemotherapy. The patient completed six cycles of
      chemotherapy. We reviewed the literature in PubMed with the following keywords:
      HPS, HIV, EBV, Hodgkin lymphoma. RESULTS: We identified four publications and two
      reviews reporting cases of HPS associated with Hodgkin lymphoma in HIV patients
      with either a positive EBV load either the presence of encoded EBV RNA in tumour
      cells. Twenty-two cases (including one pediatric case) were described. Among
      adults, mostly men, the median age was <50 years and immune suppression was
      marked with a median CD4 cell count<100 cells/ul, even in patients receiving
      HAART. When measured, EBV load in the serum was high. Prognosis was poor with a
      high mortality despite adequate treatment consisting in steroids and
      chemotherapy, with or without etoposide (Table 1). CONCLUSIONS: Our case report
      and the review of literature suggest that physicians should be aware of the
      association between EBV infection/reactivation and Hodgkin lymphoma as a cause of
      HPS in HIV patients, even if successfully treated with HAART. The pathogenesis of
      these three interrelated conditions (viral infection, oncogenesis and immunologic
      reaction) remains unclear.

PMID- 25394155
TI  - Cancer prevalence in a metropolitan HIV clinic.
AB  - INTRODUCTION: Morbidity and mortality rates from AIDs defining cancers have
      fallen significantly since the introduction of highly active antiretroviral
      therapy (HAART). Patients are now living longer with HIV and are at a greater
      risk of other HIV- and non-HIV related malignancies. We report what we believe to
      be the first UK cancer prevalence study in the modern HAART era. METHODS: A
      retrospective review of electronic clinic letters was performed for all patients
      currently receiving, and those who had died whilst receiving, their HIV care at
      our centre. Demographics of patients with pre-cancerous changes, an active or
      previous cancer were recorded. RESULTS: There were 438 active patients (369 male,
      69 female) and 18 deceased patients (12 male, 6 female) in April 2014. Thirty-six
      out of four hundred fifty-six (8%) cancer diagnoses were found overall. Thirty
      one out of four hundred thirty-eight (7%) diagnoses in active patients and 5/18
      (28%) in deceased patients. More than half of those diagnosed with cancer were
      aged 50 or over (17/31 [55%]). In active patients 17/31 (55%) were AIDs defining
      cancers, with the most common type of cancer diagnosis overall being Kaposi's
      sarcoma (12/31 [39%]). There were 5/31 (16%) cases of non-Hodgkin's lymphoma. The
      most common non-AIDs defining cancer was basal cell carcinoma of which there were
      5/31 (16%) cases, followed by squamous cell carcinoma (3/31 [10%]) and testicular
      cancer (3/31 [10%]). Other cancers included colorectal (2/31 [6%]) and prostate
      cancer (1/31 [3%]). In all five deceased patients, cancer was the cause of death.
      There were four acute presentations with an aggressive glioma, Burkitt's
      lymphoma, an undiagnosed primary lung malignancy and a late diagnosed cervical
      cancer. The fifth patient died following the recurrence of a transitional cell
      cancer of the bladder after an initial diagnosis of seven years earlier. Eighteen
      out of sixty-nine (26%) of females were found to have at least mild dyskariosis
      on cervical screening. Anal intraepithelial neoplasia was diagnosed in 4/438 (1%)
      of patients. CONCLUSIONS: Non-AIDS defining malignancies account for almost half
      of the cancers in our cohort. This number may rise further as patients live
      longer with HIV. Good communication between oncologists and HIV physicians is
      paramount to manage the complex interactions of HIV and cancer, increase HIV
      testing in cancer services and address cancer risk factors in existing HIV
      patients.

PMID- 25394156
TI  - Prevalence and predictors of malignancies in a polycentric cohort of HIV patients
      from Italy.
AB  - INTRODUCTION: HIV infected patients have a higher risk of developing cancer than
      the general population. Kaposi's sarcoma, non-Hodgkin's lymphoma, primary CNS
      lymphoma and invasive cervical cancers are considered as AIDS defining [1]. An
      increased incidence in recent years has been reported also for other malignancies
      after the introduction of cART [2,3]. MATERIALS AND METHODS: We performed a
      retrospective multicentric evaluation of all HIV infected patients with both AIDS
      and non-AIDS defining neoplasms at six Infectious Disease Units spread throughout
      Italy since 1991 through 2013. Cases were compared with equal number of controls
      without neoplasia followed at the same institutions, matched for length of HIV
      infection. RESULTS: Since 1991, 339 consecutive cases of malignancy were
      collected from the six convening centres, including approximately an equal
      proportion of AIDS (51.2%) and non-AIDS defining tumours. Mean prevalence of
      tumours among centres was 8.3% (r. 6.1%-9.6%). Mean age at tumour diagnosis was
      significantly lower than in controls (42.6+/-11.0 vs 46.8+/-10.6 years,
      respectively, p<0.0001). As to risk factors for HIV infection, approximately 1/4
      (26.1%) of patients were drug abusers, in equal proportion as in controls. A
      remarkable higher proportion of cancer patients had CD4 T-cell counts <200 c/mmc
      at time of diagnosis (45.2% vs 13.3%, p<0.0001). Seventy percent of tumours
      occurred in males; 52.8% of tumour patients were diagnosed with AIDS before and
      19.0% at the time of tumour diagnosis. Ninety (28.1%) tumour patients were dead
      at the time of data collection, a much higher proportion than among cases (12.9%,
      p<0.0001). Deaths among non-AIDS (20.8%) and AIDS defining tumour patients
      (35.0%) were significantly different (p=0.005). Predictors of AIDS defining
      tumours at the time of data collection were: male sex (57.9% vs 40.6%, p=0.004),
      CD4 T-cell counts <200 c/mmc (63.6% vs 44.1%, p<0.0001), whereas being cART
      treated at the time of tumour diagnosis was protective (38.0% vs 68.0%,
      p<0.0001). In the final multivariate model of logistic regression, male sex
      (OR=2.0, p=0.03) and not being cART treated (OR=2.5, p=0.001) held as independent
      predictors. CONCLUSIONS: Our retrospection revealed a considerably high
      proportion of non-AIDS defining tumours, apparently at rise in recent years. We
      registered high prevalence of tumours in each centre. Absence of cART seemed
      related with AIDS defining tumours: once more prevention of late presentation
      appeared the way to avoid worse prognosis in this setting.

PMID- 25394157
TI  - Increased incidence of sexually transmitted diseases in the recent years: data
      from the ICONA cohort.
AB  - INTRODUCTION: Sexually transmitted diseases (STDs) data collected in HIV+
      patients could be used as indicator of risky sexual behaviour possibly linked to
      HIV transmission. We described the STDs incidence over time and identified higher
      incidence factors. METHODOLOGY: All patients in the ICONA Foundation Study
      enrolled after 1998 were included. STDs considered: any-stage syphilis, human
      papilloma virus (HPV) diseases, gonococcal and non-gonococcal urethritis, herpes
      simplex virus (HSV) genital ulcers, vaginitis and acute hepatitis B virus (HBV),
      hepatitis A virus (HAV), and hepatitis C virus (HCV) infections (only for non
      IVDU (intravenous drug user) patients). STDs incidence rate (IR): number of STDs
      divided by person years of follow-up (PYFU). Calendar periods: 1998-2002, 2003
      2007 and 2008-2012. Predictors of STDs occurrence were identified using Poisson
      regression and sandwich estimates for the standard errors were used for multiple
      STD events. RESULTS: Data of 9,168 patients were analyzed (median age 37.3
      (SD=9.3), 74% male, 30% MSM). Over 46,736 PYFU, 996 episodes of STDs were
      observed (crude IR 17.3/1,000 PYFU). Median (IQR) CD4/mmc and HIV-RNA/mL at STD:
      433 (251-600) and 10,900 (200-63,000). Highest crude IRs were observed for any
      stage syphilis (3.95, 95% CI 3.59-4.35), HPV diseases (1.96, 1.71-2.24) and acute
      hepatitis (1.72, 1.49-1.99). At multivariable analysis (variables of adjustment
      shown in Figure 1), age (IRR 0.82 per 10 years younger, 95% CI 0.77-0.89), MSM
      contacts (IRR 3.03, 95% CI 2.52-3.64 vs heterosexual) and calendar period (IRR
      1.67, 95% CI 1.42-1.96, comparing 2008-2012 with 1998-2002) significantly
      increased the risk of acquiring STDs. Moreover, having a HIV-RNA >50 c/mL (IRR
      1.44, 95% CI 1.19-1.74 vs HIV-RNA <50 c/mL) and current CD4+ cell count <100/mmc
      (IRR 4.66, 95% CI 3.69-5.89, p<0.001 vs CD4+ cell count >500) showed an increased
      risk of STDs. Being on ARV treatment significantly reduced the risk of developing
      an STD (IRR 0.37, 95% CI 0.32-0.43) compared to ART-naive people, even in the
      situation of temporary interruption of treatment (IRR 0.51, 95% CI 0.39-0.43)
      (see Figure 1). CONCLUSIONS: The overall incidence of STDs has been increasing in
      the recent years. Interventions to prevent STDs and potential further spread of
      HIV infection should target the recently HIV diagnosed, the young population and
      MSM. Being on ARV treatment (potentially an indicator of whether a person is
      regularly seen for care) seems to reduce the risk of acquiring STDs independently
      of its viro-immunological effect.

PMID- 25394158
TI  - Predictors of lack of serological response to syphilis treatment in HIV-infected
      subjects.
AB  - INTRODUCTION: The aim of this study was to determine factors associated with lack
      of serological response (LSR) to treatment of syphilis among HIV-infected
      subjects. MATERIALS AND METHODS: Retrospective, longitudinal study on HIV
      infected subjects diagnosed and treated for syphilis and with an assessable
      serological response between 1 January 2004 and 15 September 2013. LSR was
      defined as a <4-fold decline of rapid plasma reagin (RPR) titer or a failed
      reversion to nonreactive (if RPR <=1:4 at diagnosis) after one year since
      treatment. Diagnoses of syphilis were staged in early syphilis (primary,
      secondary and early latent) or late syphilis (tertiary and late latent) according
      to clinical examination and patient's history. Syphilis was classified in new
      infections [NI: positive RPR and TPHA (Treponema pallidum Haemagglutination
      assay) titers in subjects without previous history of syphilis] or re-infections
      [ReI: a >=4-fold increase of RPR titer in subjects previously successfully
      treated for syphilis]. Syphilis treatment was prescribed according to CDC
      guidelines. The crude incidence rates (IRs) of LSR were calculated per 1000
      person months of follow-up (PMFU) as the total number of LSR episodes divided by
      the cumulative time contributed by all subjects (interval time since each
      syphilis diagnosis and the date of ascertainment of response). RESULTS are
      described as median (IQR) or frequency (%). RESULTS: 565 diagnoses of syphilis
      with an assessable serological response in 421 patients; 458 (81%) were early
      syphilis, 189 (33%) were NI, 376 (67%) were ReI. At first, diagnosis of syphilis
      median age was 41 (36-47) years, 419 (99.5%) males, 391 (93%) MSM, HIV-infected
      since 7.7 (3.5-12.9) years, 75 (18%) HCV or HBV co-infected, 56 (13%) with a
      previous AIDS diagnosis, 82 (19%) antiretroviral treatment naive, 102 (24%) with
      HIV-RNA >=50 cp/mL, CD4+=576 (437-749) cells/mm(3), nadir CD4+=308 (194-406)
      cells/mm(3). LSRs were observed in 70/565 (12.4%) treated syphilis. Incidence of
      LSR decreased over time [2004-2008 IR=25.1 (17.2-33.1)/1000 PMFU; 2009-2010
      IR=21.1 (12.3-29.9)/1000 PMFU; 2011-2013 IR=10.6 (5.1-18.2)/1000 PMFU; Poisson
      regression: p=0.001]. RESULTS of univariate and multivariate analysis on the risk
      of LSR are reported in Table 1. CONCLUSIONS: In HIV-infected subjects we observed
      12% of LSR to treatment of syphilis. LSR was associated with an older age, late
      syphilis, lower nadir CD4+ and detectable HIV viral load.

PMID- 25394159
TI  - Central nervous system penetration-effectiveness rank does not reliably predict
      neurocognitive impairment in HIV-infected individuals.
AB  - INTRODUCTION: Central nervous system (CNS) penetration-effectiveness (CPE) rank
      was proposed in 2008 as an estimate of penetration of ARV regimen into the CNS,
      and validated as predictor of CSF HIV-1 replication. RESULTS on predictive role
      of CPE on neurocognitive and clinical outcome were conflicting. MATERIALS AND
      METHODS: Retrospective, cross-sectional analysis of neurocognitive profile in HIV
      infected cART-treated patients. All patients underwent neuropsychological (NP)
      assessment by standardized battery of 14 tests on 5 different domains. People
      were classified as having NCI if they scored >1 standard deviation (SD) below the
      normal mean in at least two tests, or >2 SD below in one test. Linear and
      logistic regression analyses were fitted using as outcome Npz8 and impaired/not
      impaired respectively. RESULTS: A total of 660 HIV-infected cART-treated
      individuals from 2009 to 2014, contributing a total of 1003 tests (mean age 49
      (IQR 43-56), male 82%; median current CD4 586/mm(3); 18% HCV infected; HIV-RNA
      <40 cp/mL in 84%). Current ARV regimen was 2NRTIs+1NNRTI 50.3%, 2NRTI+1PI/r in
      32.6%, NRTI sparing in 11.1%. Mean CPE of current regimens was 6.6 (95% CI 6.5
      6.7). As per test multivariable analysis, higher CPE values were associated to
      poor NP tasks (Beta=-0,09; 95% CI -0,14 -0,03; p=0.002 at multivariable linear
      regression). The association between higher CPE and increased NCI risk was
      confirmed at multivariable logistic regression, with a 1.24-fold risk of NCI
      occurrence for each point increase of CPE of current regimen at the time of NP
      testing (see Table 1). In a sensitivity analysis performed only on patients at
      the first NP test, the association between higher CPE and poor NP tasks and
      enhanced NCI risk was only marginally confirmed (Beta=-0,05; [-0,12-0,02];
      p=0,19; OR 1,13 [0,95-1,34]; p=0.17). Older age, longer time from HIV diagnosis,
      current CD4 count <350 cell/mm(3) and lower education level were all associated
      to an increased risk of NCI. CONCLUSIONS: In our analysis, higher CPE rank is
      associated to poorly performing at NP tasking. Even if selection bias could not
      be excluded due to retrospective cross-sectional design, these results fitted
      with the direct correlation between high CPE and HIV dementia recently recorded
      in a large observational database. We think that CPE use to guide ART in patients
      neurocognitively impaired should be revised.

PMID- 25394161
TI  - Ongoing epidemic of lymphogranuloma venereum in HIV-positive men who have sex
      with men: how symptoms should guide treatment.
AB  - INTRODUCTION: Lymphogranuloma venereum (LGV) is a sexually transmitted infection
      (STI) caused by chlamydia trachomatis (CT) genotype L (L1, L2 and L3). Recent
      outbreaks of LGV in Europe and North America affected mainly men who have sex
      with men (MSM). Infections with CT serotypes D-K are mostly associated with mild
      symptoms or may be clinically silent. However, infections with L genotypes are
      more invasive and induce anogenital ulcer or inguinal lymphadenopathy. MATERIALS
      AND METHODS: Between 2003 and 2013, anal or genital CT infections were diagnosed
      in 471 symptomatic patients attending the Infectious Diseases Center Hamburg
      (ICH). CT DNA was detected by PCR. CT genotyping of positive samples was
      performed by sequence analyses of omp1 PCR products (samples between 2003 and
      2010). Samples between 2012 and 2013 were analyzed by genotype L specific real
      time PCR. RESULTS: In total, 221 LGV patients were identified (3 in 2003; 11 in
      2004; 26 in 2005; 33 in 2006; 24 in 2007; 16 in 2008; 18 in 2009; 15 in 2010; 17
      in 2011; 26 in 2012 and 32 in 2013). One hundred ninety-eight of 221 (89.6%)
      patients with LGV were HIV-infected; 10 of 221 (4.5%) were HIV-negative, and the
      HIV-status unknown in 13 (5.9%). The majority of LGV positive patients (204/221;
      92%) had anorectal symptoms (bloody proctitis, rectal pain, purulent or mucous
      discharge, tenesmus, constipation), compared to 17/221 (8%) who presented with
      genital symptoms as urethritis, genital ulcer or inguinal lymphadenopathy. Of 283
      CT-positive patients with anorectal symptoms, genotype L was detected in 205
      (72%), while non-L genotypes (D-K) were found in 78 (28%). In contrast, genotype
      L was found in only 6% of patients with genital symptoms (11/177), whereas 94%
      (166/177) were infected with non-L genotypes only. CONCLUSIONS: The epidemic of
      LGV among predominantly HIV+ MSM is ongoing. LGV might be underdiagnosed,
      especially in patients with anorectal symptoms. Infections with CT serotypes D-K
      are more often associated with urogenital symptoms or asymptomatic infection,
      whereas LGV genotypes are found most frequently in patients with
      rectal/intestinal symptoms. Anorectal CT infections in MSM should be further
      characterized by genotyping for LGV, as for LGV three weeks of doxycycline
      treatment are recommended. CT genotypes D-K generally require shorter antibiotic
      treatment. If CT genotyping is not available, the duration of treatment should be
      prolonged to three weeks empirically for CT-positive patients with anorectal or
      intestinal symptoms.

PMID- 25394160
TI  - CNS safety at 48-week of switching to ATV/r plus 3TC or two nucleos(t)ides in HIV
      suppressed patients on stable ART: the SALT neurocognitive sub-study.
AB  - INTRODUCTION: Due to their low CNS penetrance, there are concerns about the
      capacity of non-conventional PI-based ART (monotherapy and dual therapies) to
      preserve neurocognitive performance (NP). METHODS: We evaluated the NP change of
      aviremic participants of the SALT clinical trial (1) switching therapy to dual
      therapy (DT: ATV/r+3TC) or triple therapy (TT: ATV/r+2NRTI) who agreed to perform
      an NP assessment (NPZ-5) at baseline and W48. Neurocognitive impairment and NP
      were assessed using AAN-2007 criteria (2) and global deficit scores (GDS) (3).
      Neurocognitive change (GDS change: W48 - baseline) and the effect of DT on NP
      evolution crude and adjusted by significant confounders were determined using
      ANCOVA. RESULTS: A total of 158 patients were included (Table 1). They had
      shorter times because HIV diagnosis, ART initiation and HIV-suppression and their
      virologic outcome at W48 by snapshot was higher (79.1% vs 72.7%; p=0.04) compared
      to the 128 patients not included in the sub-study. By AAN-2007 criteria, 51
      patients in each ART group (68% vs 63%) were neurocognitively impaired at
      baseline (p=0.61). Forty-seven patients were not reassessed at W48: 30 lost of
      follow-up (16 DT-14 TT) and 17 had non-evaluable data (6 DT-11 TT). Patients
      retested were more likely to be men (78.9% vs 61.4%) and had neurological
      cofounders (9.6% vs 0%) than patients non-retested. At W48, 3 out of 16 (5.7%)
      patients on DT and 6 out of 21 (10.5%) on TT who were non-impaired at baseline
      became impaired (p=0.49) while 10 out of 37 (18.9%) on DT and 7 out of 36 (12.3%)
      on TT who were neurocognitively impaired at baseline became non-impaired
      (p=0.44). Mean GDS changes (95% CI) were: Overall -0.2 (-0.3 to -0.04): DT -0.26
      (-0.4 to -0.07) and TT -0.08 (-0.2 to 0.07). NP was similar between DT and TT
      (0.15). This absence of differences was also observed in all cognitive tests.
      Effect of DT: -0.16 [-0.38 to 0.06]) (r(2)=0.16) on NP evolution was similar to
      TT (reference), even after adjusting (DT: -0.11 [-0.33 to 0.1], TT: reference) by
      significant confounders (geographical origin, previous ATV use and CD4 cell
      count) (r(2)=0.25). CONCLUSIONS: NP stability was observed after 48 weeks of
      follow up in the majority of patients whether DT or TT was used to maintain HIV
      suppression. Incidence rates of NP impairment or NP impairment recovery were also
      similar between DT and TT.

PMID- 25394162
TI  - APRI and FIB-4 scores are not associated with neurocognitive impairment in HIV
      infected persons.
AB  - INTRODUCTION: Chronic liver disease leads to neurocognitive impairment (NCI) and
      more advanced liver fibrosis is associated with greater deficits. Further,
      cognitive performances do not differ significantly among patients affected by
      diverse types of chronic liver diseases. Thus, it would be useful to have a
      clinical tool associated with early cognitive change applicable to the HIV
      infected population with high HCV prevalence. Aim of the analysis was to assess
      the association between NCI and aspartate aminotransferase-platelet ratio index
      (APRI) or Fibrosis-4, which are non-invasive scores used to assess liver
      fibrosis. MATERIALS AND METHODS: Single-centre, retrospective, cross-sectional
      analysis of cART-treated HIV-infected patients undergoing neuropsychological
      assessment (NPA) by a set of 14 standardized and comprehensive tests on five
      different domains: concentration and speed of mental processing; mental
      flexibility; memory, fine motor functioning; visual-spatial and constructional
      abilities. NPA obtained from the same patient were included, if collected while
      receiving different cART. Patients were classified as having NCI, if they scored
      >1 SD below the normative mean in at least two tests, or below >2 SD in one test.
      HIV-associated neurocognitive disorders (HAND) were classified according to
      Frascati's criteria, controlling for confounding comorbidities. Univariable
      analysis and multivariable logistic regression models were carried out. RESULTS:
      A total of 556 HIV-infected cART-treated patients from 2006 to 2013 were
      included: male 78%; IVDUs 14%; CDC stage C 31%; median CD4 nadir 200/mm(3);
      median current CD4 501/mm(3); undetectable HIV-RNA in 368 (67%); and HCV
      positivity in 150 (29%). Frequency among score levels was for FIB-4: min-1.44=404
      (73%), 1.45-3.25=118 (21%), 3.26-max=28 (5%); for APRI: min-0.5=414 (75%), 0.5
      1.5=112 (20%), 1.5-max=24 (4%). Median FIB-4 and APRI were 0.98 and 0.27 in
      HIV+/HCV- and 1.40 and 0.50 in HIV+/HCV+ individuals, respectively. HAND was
      found in 176 (32%): 91 ANI, 73 MND, 12 HAD. Association of variables with NCI are
      shown in Table 1. CONCLUSIONS: In this large population, HAND was not associated
      with commonly used non-invasive liver fibrosis scores. As aetiology of cognitive
      dysfunction in HIV mono- and HCV co-infected patients is multifactorial and
      partially unknown, our results support the hypothesis of a direct or indirect
      effect on cognitive function of the viruses, rather than the consequence of
      alterations residing outside the brain.

PMID- 25394163
TI  - Low clinical relevance of risky alcohol consumption in a selected group of high
      adherent HIV-infected patients attended in the United Kingdom.
AB  - INTRODUCTION: The prevalence of risky alcohol consumption, associated factors and
      its impact on the brain is not well established in clinically stable HIV
      patients. MATERIALS AND METHODS: Within the PIVOT neurocognitive sub-study,
      effectively suppressed HIV-infected adults on either standard cART or ritonavir
      boosted PI monotherapy completed the Alcohol Use Disorders Identification Test
      (AUDIT) designed to detect risky alcohol consumption. They also completed a brief
      neuropsychological assessment (NPZ 5) composed by five measures. For this cross
      sectional analysis, we calculated rates of hazardous (AUDIT=8-15) or harmful
      (AUDIT=16-19) consumption and likely dependence (AUDIT>20). We explored the
      association between risky alcohol intakes (AUDIT>8) and clinical/demographical
      variables, conducting logistic regressions when significant association was found
      (p<.05). Also, the association between cognitive performance and alcohol
      consumption was calculated and adjusted by potential confounders. RESULTS: Of the
      146 included participants, the majority were male (86.3%), white (81.5%) and
      educated (mean years on formal education=15, SD=3.9). Average age was 47.6 years
      (SD=8.7), and 36.3% had risky consumption (29.5% hazardous, 6.2% harmful, 0.7%
      likely dependence). White ethnicity and male sex were positively associated with
      risky consumption (Table 1). After adjustments, white ethnicity remained
      significantly associated with risky consumption (1.64 [95% CI 0.34-2.95];
      p=0.013). Better cognitive performance was associated with risky alcohol
      consumption in the univariate analysis (p<.001). After adjustment by ethnicity,
      sex and years of education, cognitive performance and risky alcohol consumption
      maintained significant association (0.45 [95% CI 0.19-0.70] p=0.001).
      CONCLUSIONS: Despite the substantially high prevalence of risky alcohol
      consumption, it was not associated with worse adherence, immunological or quality
      of life measures in this cohort of effectively suppressed patients but prevalence
      of likely alcohol dependency was extremely low. White patients were more
      vulnerable to risky consumption. Moreover, positive association between cognitive
      performance and risky alcohol consumption remained after adjustment. In our
      study, the association we found between cognitive function and alcohol
      consumption does not reflect the effect of alcohol dependency on cognition.

PMID- 25394164
TI  - Predictors of emphysema progression in HIV-positive patients.
AB  - INTRODUCTION: The aim of the study was to find factors associated with emphysema
      progression (EP), assessed on sequential thoracic CT scans, in a large cohort of
      HIV-positive patients. MATERIALS AND METHODS: This was an observational,
      prospective study of 448 consecutive HIV-positive patients on antiretroviral
      therapy who underwent two sequential ECG-gated coronary artery calcium scoring CT
      scans. Images were reviewed by three radiologists by consensus to assess lung
      emphysema using a visual semi-quantitative score (0 to 4) for each of six lobes.
      EP was defined as an increase in emphysema score. Heavy smoking habit was defined
      as a self-reported number of cigarettes per day smoked greater than 10. Immune
      reconstitution was defined as the change in CD4 cell count between first CT scan
      and CD4 nadir and it was divided into tertiles. Progressors and non-progressors
      were compared using X2-test for categorical variables and T-test of Mann-Whitney
      U test for continuous variables where appropriate. Factors independently
      associated with EP were explored using multivariable logistic regression
      analyses. A p-value <.05 was considered statistically significant. RESULTS: The
      mean age of the included patients was 47,9+/-7,7 years, 24,1% of them were
      females and 39,3% were smokers. The median interval between the two CT scans was
      2,4 years (interquartile range 0,69-5,9 years). EP was significantly associated
      with HIV-infection duration (p=0,056), smoking (p=0,007) and in particular heavy
      smoking habit (p=0,015) and time interval between the two scans (p=0,021), while
      the highest tertile of immune reconstitution was borderline in significance
      (p=0,075). Age and sex were not significantly related to EP and were not included
      in further analyses. HIV infection duration (OR=1,01; p=0,013), time interval
      between the two scans (OR=1,51; p=0,032) and heavy smoking habit (OR=3,36;
      p=0,041) remained independently associated with EP in multivariate analysis.
      CONCLUSIONS: In this large cohort of HIV positive patients on antiretroviral
      therapy, HIV infection duration, time between CT scans and continued heavy
      cigarette smoking were independently associated with EP.

PMID- 25394165
TI  - Vintage progressive outer retinal necrosis - reply.

PMID- 25394166
TI  - Frequency and characteristics of intraocular inflammation after aflibercept
      injection.
AB  - PURPOSE: To report the frequency and characteristics of intraocular inflammation
      after intravitreal aflibercept injection. METHODS: A single-center retrospective
      study was performed in patients who received intravitreal aflibercept from
      November 2011 through June 2013. RESULTS: There were 28 cases of intraocular
      inflammation after a total of 5,905 aflibercept injections among 1,660 patients.
      The mean baseline acuity was 20/57, which decreased to 20/179 at diagnosis (P <
      0.0001) but recovered to 20/59 at Month 1, 20/57 at Month 3, and 20/52 at Month 6
      (P = not significant). Vitreous culture and injection of antibiotics were
      performed in eight cases, and all were culture negative; the remainder received
      only topical corticosteroids. CONCLUSION: The frequency of inflammation after
      aflibercept was 0.47% per injection. Visual acuity and inflammation returned to
      baseline within 1 month in most cases with topical corticosteroid treatment.

PMID- 25394167
TI  - Malnutrition in the nursing home.
AB  - PURPOSE OF REVIEW: Malnutrition in the nursing home is increasingly recognized as
      a major international research priority, given the expanding geriatric
      populations, serious consequences, and challenges conducting research in nursing
      homes. This review examines the recent literature and suggests implications for
      research and practice. RECENT FINDINGS: Across the recent studies, approximately
      20% of nursing home residents had some form of malnutrition. However,
      malnutrition definitions were variable and prevalence ranged from 1.5 to 66.5%.
      Depression, cognitive impairment, functional impairment, and swallowing
      difficulty were consistently associated with malnutrition. Mortality was the
      major consequence of malnutrition among nursing home residents, whereas higher
      BMIs had lower risks of mortality. Beneficial interventions to reduce
      malnutrition in the nursing home included dietary supplements, greater resident
      role in food choice, and staff training programs. SUMMARY: To truly tackle the
      issue of malnutrition in the nursing home setting, a consistent definition is
      needed. We strongly recommend that an expert consensus panel identify a standard
      set of measures to more accurately compare the prevalence across countries. Given
      the mortality consequences of malnutrition and the paucity of intervention
      studies, research on interventions for malnutrition in the nursing home needs to
      be a higher priority for facilities, researchers, and funding agencies.

PMID- 25394168
TI  - An epistemological shift: from evidence-based medicine to epistemological
      responsibility.
AB  - In decision making concerning the diagnosis and treatment of patients, doctors
      have a responsibility to do this to the best of their abilities. Yet we argue
      that the current paradigm for best medical practice - evidence-based medicine
      (EBM) - does not always support this responsibility. EBM was developed to promote
      a more scientific approach to the practice of medicine. This includes the use of
      randomized controlled trials in the testing of new treatments and prophylactics
      and rule-based reasoning in clinical decision making. But critics of EBM claim
      that such a scientific approach does not always work in the clinic. In this
      article, we build on this critique and argue that rule-based reasoning and the
      use of general guidelines as promoted by EBM does not accommodate the complex
      reasoning of doctors in clinical decision making. Instead, we propose that a new
      medical epistemology is needed that accounts for complex reasoning styles in
      medical practice and at the same time maintains the quality usually associated
      with 'scientific'. The medical epistemology we propose conforms to the
      epistemological responsibility of doctors, which involves a specific professional
      attitude and epistemological skills. Instead of deferring part of the
      professional responsibility to strict clinical guidelines, as EBM allows for, our
      alternative epistemology holds doctors accountable for epistemic considerations
      in clinical decision making towards the diagnosis and treatment plan of
      individual patients. One of the key intellectual challenges of doctors is the
      ability to bring together heterogeneous pieces of information to construct a
      coherent 'picture' of a specific patient. In the proposed epistemology, we
      consider this 'picture' as an epistemological tool that may then be employed in
      the diagnosis and treatment of a specific patient.

PMID- 25394169
TI  - Toddler's self-regulation strategies in a challenge context are nap-dependent.
AB  - Early childhood represents a time of developmental changes in both sleep and self
      regulation, a construct reflecting the ability to control one's behaviour,
      attention and emotions when challenged. Links between sleep and self-regulation
      processes have been proposed, but experimental evidence with young children is
      lacking. In the current study, we tested the effects of acute sleep restriction
      (nap deprivation) on toddlers' self-regulation. Healthy children (n = 12; four
      males; aged 30-36 months (33.9 +/- 1.7)) slept on a strict schedule (verified
      with actigraphy and sleep diaries) for 5 days before each of two afternoon
      assessments following a nap and a no-nap condition (~11-day protocol). Children
      were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive
      self-regulation strategies were later coded. On average, children lost ~90 min of
      sleep on the no-nap versus the nap day. Nap deprivation resulted in moderate-to
      large effects on self-regulation strategies, with decreases in scepticism (d =
      0.77; 7% change), negative self-appraisal (d = 0.92; 5% change) and increases in
      physical self-soothing (d = 0.68; 10% change), focus on the puzzle piece that
      would not fit (perseveration; d = 0.50; 9% change) and insistence on completing
      the unsolvable puzzle (d = 0.91; 10% change). Results suggest that sleep serves
      an important role in the way that toddlers respond to challenging events in their
      daily lives. After losing daytime sleep, toddlers were less able to engage
      effectively in a difficult task and reverted to less mature self-regulation
      strategies than when they were well rested. Over time, chronically missed sleep
      may impair young children's self-regulation abilities, resulting in risk for
      social-emotional, behavioural and school problems.

PMID- 25394170
TI  - Isoflavone content and profile comparisons of cooked soybean-rice mixtures:
      electric rice cooker versus electric pressure rice cooker.
AB  - This study examined the effects of heat and pressure on the isoflavone content
      and profiles of soybeans and rice cooked together using an electric rice cooker
      (ERC) and an electric pressure rice cooker (EPRC). The total isoflavone content
      of the soybean-rice mixture after ERC and EPRC cooking relative to that before
      cooking was ~90% in soybeans and 14-15% in rice. Malonylglucosides decreased by
      an additional ~20% in EPRC-cooked soybeans compared to those cooked using the
      ERC, whereas glucosides increased by an additional ~15% in EPRC-cooked soybeans
      compared to those in ERC-cooked soybeans. In particular, malonylgenistin was
      highly susceptible to isoflavone conversion during soybean-rice cooking. Total
      genistein and total glycitein contents decreased in soybeans after ERC and EPRC
      cooking, whereas total daidzein content increased in EPRC-cooked soybeans (p <
      0.05). These results may be useful for improving the content of nutraceuticals,
      such as isoflavones, in soybeans. 

PMID- 25394171
TI  - The cost-effectiveness of returning incidental findings from next-generation
      genomic sequencing.
AB  - PURPOSE: The American College of Medical Genetics and Genomics (ACMG) recommended
      that clinical laboratories performing next-generation sequencing analyze and
      return pathogenic variants for 56 specific genes it considered medically
      actionable. Our objective was to evaluate the clinical and economic impact of
      returning these results. METHODS: We developed a decision-analytic policy model
      to project the quality-adjusted life-years and lifetime costs associated with
      returning ACMG-recommended incidental findings in three hypothetical cohorts of
      10,000 patients. RESULTS: Returning incidental findings to cardiomyopathy
      patients, colorectal cancer patients, or healthy individuals would increase costs
      by $896,000, $2.9 million, and $3.9 million, respectively, and would increase
      quality-adjusted life-years by 20, 25.4, and 67 years, respectively, for
      incremental cost-effectiveness ratios of $44,800, $115,020, and $58,600,
      respectively. In probabilistic analyses, returning incidental findings cost less
      than $100,000/quality-adjusted life-year gained in 85, 28, and 91%, respectively,
      of simulations. Assuming next-generation sequencing costs $500, the incremental
      cost-effectiveness ratio for primary screening of healthy individuals was
      $133,400 (<$100,000/quality-adjusted life-year gained in 10% of simulations).
      Results were sensitive to the cohort age and assumptions about gene penetrance.
      CONCLUSION: Returning incidental findings is likely cost-effective for certain
      patient populations. Screening of generally healthy individuals is likely not
      cost-effective based on current data, unless next-generation sequencing costs
      less than $500.

PMID- 25394173
TI  - Reporting genomic secondary findings: ACMG members weigh in.
AB  - PURPOSE: The aim of this study was to survey American College of Medical Genetics
      and Genomics members about secondary findings from clinical genome-scale
      sequencing. METHODS: A Web-based survey was mailed to 1,687 members of the
      American College of Medical Genetics and Genomics. Exploratory factor analysis
      identified underlying factors assessed by survey items. Linear regression
      assessed associations between factor scores and respondent characteristics.
      RESULTS: The response rate was 29%. Four factors explained 51% of the survey
      variance: best practices, patient preferences, guidance, and informed consent.
      Most agreed with "best practice" items describing seeking and reporting of
      secondary findings as consistent with medical standards, having sufficient
      evidence, and, for adults, the benefits generally outweighing potential harms.
      There was lack of agreement regarding benefits versus harms for children and
      impact on health-care resources. The majority agreed that patient preferences
      should be considered, including ability to opt out, and that informed consent was
      feasible and critical. Characteristics significantly associated with factor
      scores included country of residence, sequencing experience, and years in
      practice. CONCLUSION: The American College of Medical Genetics and Genomics
      should update a list of genes to be assessed when clinical genome-scale
      sequencing is performed. Informed consent is necessary, and reporting of
      secondary findings should be optional. Research on implementation of secondary
      findings reporting is needed.

PMID- 25394172
TI  - Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a
      clinical entity with a high frequency of FGFR1 mutations.
AB  - PURPOSE: Congenital hypogonadotropic hypogonadism (CHH) and split hand/foot
      malformation (SHFM) are two rare genetic conditions. Here we report a clinical
      entity comprising the two. METHODS: We identified patients with CHH and SHFM
      through international collaboration. Probands and available family members
      underwent phenotyping and screening for FGFR1 mutations. The impact of identified
      mutations was assessed by sequence- and structure-based predictions and/or
      functional assays. RESULTS: We identified eight probands with CHH with (n = 3;
      Kallmann syndrome) or without anosmia (n = 5) and SHFM, seven of whom (88%)
      harbor FGFR1 mutations. Of these seven, one individual is homozygous for p.V429E
      and six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A,
      p.V688L, or p.L712P. All mutations were predicted by in silico analysis to cause
      loss of function. Probands with FGFR1 mutations have severe gonadotropin
      releasing hormone deficiency (absent puberty and/or cryptorchidism and/or
      micropenis). SHFM in both hands and feet was observed only in the patient with
      the homozygous p.V429E mutation; V429 maps to the fibroblast growth factor
      receptor substrate 2alpha binding domain of FGFR1, and functional studies of the
      p.V429E mutation demonstrated that it decreased recruitment and phosphorylation
      of fibroblast growth factor receptor substrate 2alpha to FGFR1, thereby resulting
      in reduced mitogen-activated protein kinase signaling. CONCLUSION: FGFR1 should
      be prioritized for genetic testing in patients with CHH and SHFM because the
      likelihood of a mutation increases from 10% in the general CHH population to 88%
      in these patients.

PMID- 25394174
TI  - Inbreeding among Caribbean Hispanics from the Dominican Republic and its effects
      on risk of Alzheimer disease.
AB  - BACKGROUND: Inbreeding can be associated with a modification of disease risk due
      to excess homozygosity of recessive alleles affecting a wide range of phenotypes.
      We estimated the inbreeding coefficient in Caribbean Hispanics and examined its
      effects on risk of late-onset Alzheimer disease. METHODS: The inbreeding
      coefficient was calculated in 3,392 subjects (1,451 late-onset Alzheimer disease
      patients and 1,941 age-matched healthy controls) of Caribbean Hispanic ancestry
      using 177,997 nearly independent single-nucleotide polymorphisms from genome-wide
      array. The inbreeding coefficient was estimated using the excess homozygosity
      method with and without adjusting for admixture. RESULTS: The average inbreeding
      coefficient in Caribbean Hispanics without accounting for admixture was F = 0.018
      (+/-0.048), suggesting a mating equivalent to that of second cousins or second
      cousins once removed. Adjusting for admixture from three parent populations, the
      average inbreeding coefficient was found to be 0.0034 (+/-0.019) or close to
      third-cousin mating. Inbreeding coefficient was a significant predictor of
      Alzheimer disease when age, sex, and APOE genotype were used as adjusting
      covariates (P = 0.03). CONCLUSION: The average inbreeding coefficient of this
      population is significantly higher than that of the general Caucasian populations
      in North America. The high rate of inbreeding resulting in increased frequency of
      recessive variants is advantageous for the identification of rare variants
      associated with late-onset Alzheimer disease.Genet Med 17 8, 639-643.

PMID- 25394177
TI  - The combination of bortezomib with enzastaurin or lenalidomide enhances
      cytotoxicity in follicular and mantle cell lymphoma cell lines.
AB  - We analyzed the combination of a proteasome inhibitor (bortezomib) with
      enzastaurin (PKC/AKT-inhibitor) or lenalidomide (immunomodulatory agent) for the
      inhibition of proliferation and induction of apoptosis in B-cell lymphoma cell
      lines and primary malignant cells. The effects of bortezomib, enzastaurin or
      lenalidomide, alone or in combinations, on cell viability and apoptosis were
      evaluated using the Cell Proliferation Kit and flow cytometry analysis. The
      interaction between drugs was examined by the Chou-Talalay method. Cell cycle
      analysis was performed by flow cytometry. The PI3K/AKT, PKC and MAPK/ERK
      signaling pathways were analyzed using western blot. Bortezomib with either
      enzastaurin or lenalidomide synergistically induced anti-proliferative and pro
      apoptotic effects in B-cell lymphoma cells, even in the presence of the bone
      marrow microenvironment. The direct cytotoxicity is mediated by signaling events
      involving the PI3K/AKT, PKC and MAPK/ERK pathways leading to cell death. The
      significant increase of apoptosis was mediated by an increased ratio of pro
      apoptotic proteins (Bax, Bad and Bim) to anti-apoptotic proteins (Bcl-2, Bcl-xL
      and Mcl-1), triggering the cleavage of caspases -3, -9, -8 and PARP. Further
      evaluation of the combination of bortezomib with enzastaurin or lenalidomide for
      the treatment of B-cell lymphoma is warranted, with the goal to improve the
      quality of life and survival of patients.

PMID- 25394175
TI  - A practice guideline from the American College of Medical Genetics and Genomics
      and the National Society of Genetic Counselors: referral indications for cancer
      predisposition assessment.
AB  - DISCLAIMER: The practice guidelines of the American College of Medical Genetics
      and Genomics (ACMG) and the National Society of Genetic Counselors (NSGC) are
      developed by members of the ACMG and NSGC to assist medical geneticists, genetic
      counselors, and other health-care providers in making decisions about appropriate
      management of genetic concerns, including access to and/or delivery of services.
      Each practice guideline focuses on a clinical or practice-based issue and is the
      result of a review and analysis of current professional literature believed to be
      reliable. As such, information and recommendations within the ACMG and NSGC joint
      practice guidelines reflect the current scientific and clinical knowledge at the
      time of publication, are current only as of their publication date, and are
      subject to change without notice as advances emerge. In addition, variations in
      practice, which take into account the needs of the individual patient and the
      resources and limitations unique to the institution or type of practice, may
      warrant approaches, treatments, and/or procedures that differ from the
      recommendations outlined in this guideline. Therefore, these recommendations
      should not be construed as dictating an exclusive course of management, nor does
      the use of such recommendations guarantee a particular outcome. Genetic
      counseling practice guidelines are never intended to displace a health-care
      provider's best medical judgment based on the clinical circumstances of a
      particular patient or patient population. Practice guidelines are published by
      the ACMG or the NSGC for educational and informational purposes only, and neither
      the ACMG nor the NSGC "approve" or "endorse" any specific methods, practices, or
      sources of information.Cancer genetic consultation is an important aspect of the
      care of individuals at increased risk of a hereditary cancer syndrome. Yet
      several patient, clinician, and system-level barriers hinder identification of
      individuals appropriate for cancer genetics referral. Thus, the purpose of this
      practice guideline is to present a single set of comprehensive personal and
      family history criteria to facilitate identification and maximize appropriate
      referral of at-risk individuals for cancer genetic consultation. To develop this
      guideline, a literature search for hereditary cancer susceptibility syndromes was
      conducted using PubMed. In addition, GeneReviews and the National Comprehensive
      Cancer Network guidelines were reviewed when applicable. When conflicting
      guidelines were identified, the evidence was ranked as follows: position papers
      from national and professional organizations ranked highest, followed by
      consortium guidelines, and then peer-reviewed publications from single
      institutions. The criteria for cancer genetic consultation referral are provided
      in two formats: (i) tables that list the tumor type along with the criteria that,
      if met, would warrant a referral for a cancer genetic consultation and (ii) an
      alphabetical list of the syndromes, including a brief summary of each and the
      rationale for the referral criteria that were selected. Consider referral for a
      cancer genetic consultation if your patient or any of their first-degree
      relatives meet any of these referral criteria.

PMID- 25394176
TI  - Toward an improved definition of the genetic and tumor spectrum associated with
      SDH germ-line mutations.
AB  - The tricarboxylic acid, or Krebs, cycle is central to the cellular metabolism of
      sugars, lipids, and amino acids; it fuels the mitochondrial respiratory chain for
      energy generation. In the past decade, mutations in the Krebs-cycle enzymes
      succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase have
      been documented to be causally involved in carcinogenesis. This review is focused
      on the relationship between SDH mutations and the carcinogenic phenotype. The
      succinate dehydrogenase complex catalyzes the oxidation of succinate to fumarate;
      mutations in its subunits SDHA, SDHB, SDHC, and SDHD, and in the assembly factor
      SDHAF2, result in syndromes with distinct tumor types, including
      pheochromocytoma/paraganglioma, gastrointestinal stromal tumor, and, less often,
      renal-cell carcinoma and pituitary adenoma. In this study we collected all
      previously reported SDH mutations with the aim of defining their nature and tumor
      spectrum. In addition, genotype-phenotype correlations as well as mechanisms of
      biallelic inactivation were analyzed in the SDH-deficient setting. Finally, we
      performed bioinformatics analysis using SIFT, Polyphen2, and Mutation Assessor to
      predict the functional impact of nonsynonymous mutations. The prediction of the
      latter was further compared with available SDHA and/or SDHB immunohistochemistry
      data.

PMID- 25394178
TI  - Functional components of bamboo shavings and bamboo leaf extracts and their
      antioxidant activities in vitro.
AB  - This study was designed to detect characteristic compounds and evaluate the free
      radical scavenging capacity of the bamboo leaves extract and bamboo shavings
      extract (BSE). The antioxidant capacity of bamboo leaf n-butanol fraction (AOB)
      exhibited the highest total phenolic content (49.93%), total flavonoids content
      (24.11%), and characteristic flavonoids and phenolic acids, such as chlorogenic
      acid, caffeic acid, ferulic acid, p-coumaric acid, orientin, homoorientin,
      vitexin, and isovitexin. Available data obtained with in vitro models suggested
      that AOB had higher free radical scavenging capacity with IC(50) values of 1.04,
      4.48, 5.37, and 1.12 MUg/mL on DPPH(*), O(2)(*-), (*)OH, and H(2)O(2),
      respectively, than the other two extracts, bamboo leaf water extract and BSE. The
      results indicated that the extracts from different parts of the bamboo possess
      excellent antioxidant activity, which can be used potentially as a readily
      accessible and valuable bioactive source of natural antioxidants.

PMID- 25394180
TI  - Inhibitors of polyhydroxyalkanoate (PHA) synthases: synthesis, molecular docking,
      and implications.
AB  - Polyhydroxyalkanoate (PHA) synthases (PhaCs) catalyze the formation of
      biodegradable PHAs that are considered to be ideal alternatives to non
      biodegradable synthetic plastics. However, study of PhaCs has been challenging
      because the rate of PHA chain elongation is much faster than that of initiation.
      This difficulty, along with lack of a crystal structure, has become the main
      hurdle to understanding and engineering PhaCs for economical PHA production. Here
      we report the synthesis of two carbadethia CoA analogues--sT-CH2-CoA (26 a) and
      sTet-CH2-CoA (26 b)--as well as sT-aldehyde (saturated trimer aldehyde, 29), as
      new PhaC inhibitors. Study of these analogues with PhaECAv revealed that 26 a/b
      and 29 are competitive and mixed inhibitors, respectively. Both the CoA moiety
      and extension of PHA chain will increase binding affinity; this is consistent
      with our docking study. Estimation of the Kic values of 26 a and 26 b predicts
      that a CoA analogue incorporating an octameric hydroxybutanoate (HB) chain might
      facilitate the formation of a kinetically well-behaved synthase.

PMID- 25394182
TI  - Atlas stumbled: kinesin light chain-1 variant E triggers a vicious cycle of
      axonal transport disruption and amyloid-beta generation in Alzheimer's disease.
AB  - Substantial evidence implicates fast axonal transport (FAT) defects in
      neurodegeneration. In Alzheimer's disease (AD), it is controversial whether
      transport defects cause or arise from amyloid-beta (Abeta)-induced toxicity.
      Using a novel, unbiased genetic screen, Morihara et al. identified kinesin light
      chain-1 splice variant E (KLC1vE) as a modifier of Abeta accumulation. Here, we
      propose three mechanisms to explain this causal role. First, KLC1vE reduces APP
      transport, leading to Abeta accumulation. Second, reduced transport of APP by
      KLC1vE triggers an ER stress response that activates the amyloidogenic pathway.
      Third, KLC1vE impairs transport of other KLC1 cargos that regulate
      amyloidogenesis, promoting Abeta retention within the secretory pathway.
      Collectively, KLC1vE perpetuates a vicious cycle of Abeta generation, kinase
      dysregulation, and global FAT impairment that inevitably leads to cellular
      toxicity. These concepts implicate alternative splicing of KLC1 in AD and suggest
      that the reciprocal influence of transport mechanisms on disease states
      contributes to neurodegeneration. 

PMID- 25394181
TI  - Removal of cerebrospinal fluid partial volume effects in quantitative
      magnetization transfer imaging using a three-pool model with nonexchanging water
      component.
AB  - PURPOSE: Parameters of the two-pool model describing magnetization transfer (MT)
      in macromolecule-rich tissues may be significantly biased in partial volume (PV)
      voxels containing cerebrospinal fluid (CSF). The purpose of this study was to
      develop a quantitative MT (qMT) method that provides indices insensitive to CSF
      PV averaging. THEORY AND METHODS: We propose a three-pool MT model, in which PV
      macro-compartment is modeled as an additional nonexchanging water pool. We
      demonstrate the feasibility of model parameter estimation from several MT
      weighted spoiled gradient echo datasets. We validated the three-pool model in
      numerical, phantom, and in vivo studies. RESULTS: PV averaging with the free
      water compartment reduces all qMT parameters, most significantly affecting
      macromolecular proton fraction (MPF) and cross-relaxation rate. Monte-Carlo
      simulations confirmed stability of the three-pool model fit. Unlike the standard
      two-pool model, the three-pool model qMT parameters were not affected by PV
      averaging in simulations and phantom studies. The three-pool model fit allowed
      CSF PV correction in brain PV voxels and resulted in good correlation with
      standard two-pool model parameters in non-PV voxels. CONCLUSION: Quantitative MT
      imaging based on a three-pool model with a non-exchanging water component yields
      a set of CSF-insensitive qMT parameters, which may improve MPF-based assessment
      of myelination in structures strongly affected by CSF PV averaging such as brain
      gray matter.

PMID- 25394183
TI  - Regulatory elements retained during chordate evolution: coming across tunicates.
AB  - Understanding the role of conserved noncoding elements (CNEs) throughout the
      genome is taking advantage of the improved efficiency of genome-sequencing
      techniques and bioinformatics tools. Tunicates diverged before the vertebrate
      whole genome duplications and, therefore, represent an optimal model system to
      study the evolution of complex regulatory networks. Here, we review the current
      knowledge on the characterization of CNEs during embryonic development, focusing
      on the evolutionary similarity and divergence between tunicates and other
      chordates. Many vertebrate specific CNEs that regulate developmental processes
      were identified based on high level of sequence conservation, but only few of
      them have been recognized in tunicates or other invertebrates because of genomic
      sequences divergence. We discuss recent studies demonstrating that a combination
      of different methodologies, based not only on high sequence identity, can
      collectively be used to identify CNEs with regulatory activity in
      phylogenetically distant species. Here, a low sequence constraints approach was
      successfully used to search orthologous chordate gene regions for cross-species
      conserved regulatory elements that control developmental genes.

PMID- 25394184
TI  - Drosophila melanogaster brain invasion: pathogenic Wolbachia in central nervous
      system of the fly.
AB  - The pathogenic Wolbachia strain wMelPop rapidly over-replicates in the brain,
      muscles, and retina of Drosophila melanogaster, causing severe tissue
      degeneration and premature death of the host. The unique features of this
      endosymbiont make it an excellent tool to be used for biological control of
      insects, pests, and vectors of human diseases. To follow the dynamics of
      bacterial morphology and titer in the nerve cells we used transmission electron
      microscopy of 3-d-old female brains. The neurons and glial cells from central
      brain of the fly had different Wolbachia titers ranging from single bacteria to
      large accumulations, tearing cell apart and invading extracellular space. The
      neuropile regions of the brain were free of wMelPop. Wolbachia tightly interacted
      with host cell organelles and underwent several morphological changes in nerve
      cells. Based on different morphological types of bacteria described we propose
      for the first time a scheme of wMelPop dynamics within the somatic tissue of the
      host. 

PMID- 25394185
TI  - Evaluation of the combination of a dispersive liquid-liquid microextraction
      method with micellar electrokinetic chromatography coupled to mass spectrometry
      for the determination of estrogenic compounds in milk and yogurt.
AB  - In this work, the suitability of a methodology based on dispersive liquid-liquid
      microextraction (DLLME) has been evaluated for the extraction of four
      endoestrogens (estriol, 17alpha-estradiol, 17beta-estradiol, and estrone), an
      exoestrogen (17alpha-etynylestradiol), and a mycotoxin (zearalenone), together
      with some of their major metabolites (2-methoxyestradiol, alpha-zearalanol, beta
      zearalanol, alpha-zearalenol, and beta-zearalenol) from different types of milk
      (whole and skimmed cow milk and semiskimmed goat milk) and whole natural yogurt.
      The methodology includes a previous protein precipitation with acidified ACN and
      a defatting step with n-hexane. Separation of the analytes, determination, and
      quantification were developed by MEKC coupled to ESI-MS using a BGE containing an
      aqueous solution of ammonium perfluorooctanoate as MS friendly surfactant.
      Calibration, precision, and accuracy studies of the described DLLME-MEKC-MS/MS
      method were evaluated obtaining a good linearity and LODs in the low micrograms
      per liter range. 

PMID- 25394186
TI  - Cobalt-manganese-based spinels as multifunctional materials that unify catalytic
      water oxidation and oxygen reduction reactions.
AB  - Recently, there has been much interest in the design and development of
      affordable and highly efficient oxygen evolution reaction (OER) and oxygen
      reduction reaction (ORR) catalysts that can resolve the pivotal issues that
      concern solar fuels, fuel cells, and rechargeable metal-air batteries. Here we
      present the synthesis and application of porous CoMn2 O4 and MnCo2 O4 spinel
      microspheres as highly efficient multifunctional catalysts that unify the
      electrochemical OER with oxidant-driven and photocatalytic water oxidation as
      well as the ORR. The porous materials were prepared by the thermal degradation of
      the respective carbonate precursors at 400  degrees C. The as-prepared spinels
      display excellent performances in electrochemical OER for the cubic MnCo2 O4
      phase in comparison to the tetragonal CoMn2 O4 material in an alkaline medium.
      Moreover, the oxidant-driven and photocatalytic water oxidations were performed
      and they exhibited a similar trend in activity to that of the electrochemical
      OER. Remarkably, the situation is reversed in ORR catalysis, that is, the oxygen
      reduction activity and stability of the tetragonal CoMn2 O4 catalyst outperformed
      that of cubic MnCo2 O4 and rivals that of benchmark Pt catalysts. The superior
      catalytic performance and the remarkable stability of the unifying materials are
      attributed to their unique porous and robust microspherical morphology and the
      intrinsic structural features of the spinels. Moreover, the facile access to
      these high-performance materials enables a reliable and cost-effective production
      on a large scale for industrial applications. 

PMID- 25394187
TI  - A mixture of environmental organic contaminants in lake sediments affects
      hatching from Daphnia resting eggs.
AB  - Despite the relevance of resting eggs for ecology and evolution of many aquatic
      organisms and their exposure to contaminants accumulating in sediments,
      ecotoxicological studies using resting eggs are vastly underrepresented. The
      authors established a method to perform exposure assays with resting eggs
      produced by the Daphnia longispina species complex, key species in large lake
      ecosystems. A mixture of organic contaminants previously detected in sediments of
      Lake Greifensee was selected to test the potential effect of organic contaminants
      present in sediments on the hatching process. Resting eggs were exposed to a mix
      of 10 chemicals, which included corrosion inhibitors, biocides, pesticides, and
      personal care products, for a period of 15 d. Using an automated counting
      software, the authors found a significant increase in hatching success in the
      exposed resting eggs compared with controls. Such an effect has not yet been
      reported from ecotoxicological assays with resting eggs. Possible mechanistic
      explanations as well as the potential implications on the ecology and evolution
      of aquatic species that rely on a resting egg banks are discussed. Observed
      increased mortality and developmental abnormalities for hatchlings in the
      exposure treatments can be explained by toxic contaminant concentrations. The
      results of the present study highlight the need for additional studies assessing
      the effects of organic contaminants on resting egg banks and aquatic ecosystems.

PMID- 25394188
TI  - Development of a convenient ex vivo model for the study of the transcorneal
      permeation of drugs: histological and permeability evaluation.
AB  - In this paper, an ex vivo model for the study of the transcorneal permeation of
      drugs, based on porcine tissues, was evaluated. The setup is characterized by
      ease of realization, absence of O2 and CO2 bubbling and low cost; additionally,
      the large availability of porcine tissue permits a high throughput. Histological
      images showed the comparability between porcine and human corneas and confirmed
      the effectiveness of the isolation procedure. A new de-epithelization procedure
      based on a thermal approach was also set up to simulate cornea permeability in
      pathological conditions. The procedure did not affect the integrity of the
      underlying layers and allowed the characterization of the barrier properties of
      epithelium and stroma. Six compounds with different physicochemical properties
      were tested: fluorescein, atenolol, propranolol, diclofenac, ganciclovir and
      lidocaine. The model highlighted the barrier function played by epithelium toward
      the diffusion of hydrophilic compounds and the permselectivity with regard to
      more lipophilic molecules. In particular, positively charged compounds showed a
      significantly higher transcorneal permeability than negatively charged compounds.
      The comparability of results with literature data supports the goodness and the
      robustness of the model, especially taking into account the behavior of
      fluorescein, which is generally considered a marker of tissue integrity.

PMID- 25394189
TI  - Comparison of analytical and clinical performances of the digene HC2 HPV DNA
      assay and the INNO-LiPA HPV genotyping assay for detecting high-risk HPV
      infection and cervical neoplasia among HIV-positive African women.
AB  - OBJECTIVES: To compare the Hybrid Capture 2 human papillomaviruses (HPV) DNA
      assay (HC2) and the INNO-LiPA HPV Genotyping Extra assay (INNO-LiPA) for cervical
      cancer screening in HIV-1-infected African women. DESIGN: The tests were compared
      for agreement in detecting high-risk HPV (hr-HPV) and performance to detect
      squamous intraepithelial lesions (SIL), by cytology, and cervical intraepithelial
      neoplasia, by histology, in cervical samples from 1224 women in Burkina Faso (N =
      604) and South Africa (N = 620). RESULTS: When considering the 13 hr-HPV types
      detected by HC2, 634 (51.8%) and 849 (69.4%) samples were positive by HC2 and
      INNO-LiPA, respectively. Agreement between assays was 73.9% [adjusted kappa
      coefficient value, 0.44 (95% confidence interval: 0.43 to 0.53)]. Agreement
      improved with analysis restricted to women with high-grade cervical lesions
      [adjusted kappa coefficient value, 0.83 (95% confidence interval: 0.74 to 0.91)].
      The prevalence of hr-HPV, as determined by HC2 and INNO-LiPA, was 34.5% and
      54.5%, respectively, in samples with normal cytology, 48.0% and 68.0%,
      respectively, in samples with atypical squamous cells of undetermined
      significance, 51.8% and 75.2%, respectively, in samples with low-grade SIL, and
      86.3% and 89.8%, respectively, in samples with high-grade SIL/atypical squamous
      cells that cannot exclude HSIL. Sensitivity, specificity, positive, and negative
      predictive values for the diagnosis of histological high-grade lesions (CIN2+)
      were 88.8%, 55.2%, 24.7% and 96.7%, and 92.5%, 35.1%, 19.1% and 96.6% for HC2 and
      INNO-LiPA, respectively. CONCLUSIONS: HC2 has lower analytical sensitivity but
      higher specificity than INNO-LiPA for diagnosing high-grade lesions; the 2 tests
      presented a comparable clinical sensitivity. HC2 might be suitable for cervical
      cancer screening in HIV-1-infected African women, but its use in resource-limited
      settings merits to be further evaluated in comparison with other prevention
      strategies.

PMID- 25394190
TI  - Performance of rapid HIV testing by lay counselors in the field during the
      behavioral and biological surveillance survey among female sex workers and men
      who have sex with men in Botswana.
AB  - : The study assessed the performance of rapid HIV testing with whole blood using
      Kehua Bio-engineering HIV (1 + 2) and Uni-Gold HIV test kits by trained and
      certified lay counselors, offered to female sex workers and men who have sex with
      men during the 2012 survey fieldwork. The results of rapid HIV testing were
      compared with enzyme-linked immunosorbent assay testing performed in a parallel
      algorithm at the HIV Reference Laboratory. The sensitivity and the specificity of
      rapid HIV testing were high for men who have sex with men and female sex workers,
      with 98.1% and 100%, and 98.2% and 98.5%, respectively. Misclassifications
      occurred with rapid testing. 

PMID- 25394192
TI  - Monitoring outcomes for newly diagnosed and prevalent HIV cases using a care
      continuum created with New York city surveillance data.
AB  - BACKGROUND: The HIV care continuum has been used to show the proportion of
      persons living with HIV/AIDS (PWHA) who are engaged in each stage of HIV care. We
      present 1 care continuum for persons newly diagnosed with HIV and 1 for PWHA
      using New York City HIV surveillance registry data. METHODS: Persons newly
      diagnosed with HIV in 2011 or PWHA as of December 31, 2011, were included. We
      constructed each continuum for persons engaged at each stage of HIV care and
      calculated the proportion achieving each step as both dependent on or independent
      of preceding steps. RESULTS: Of the 3408 newly diagnosed persons, 67% had timely
      linkage to care (<=3 months after diagnosis), 58% were established in care 3-9
      months after timely linkage, and 43% achieved viral suppression (<=200 copies/mL)
      <=6 months after establishment in care; losses were highest from diagnosis to
      linkage. Independent measures showed 84% linked, 72% established, and 61%
      suppressed <=18 months after diagnosis. Of the 87,268 PWHA, 83% were in care in
      2011 (>=1 visit), 70% retained in care (>=2 visits >=3 months apart), and 52%
      suppressed at their last visit; losses were highest from retention to
      suppression. When measured independently, suppression increased to 58%.
      CONCLUSIONS: A minority of persons newly diagnosed with HIV and a narrow majority
      of PWHA achieved viral suppression and all intermediate care-related steps.
      Outcomes measured independently of previous care-related steps were higher,
      particularly for newly diagnosed persons. To improve outcomes among persons with
      HIV and reduce transmissibility, clinical and public health efforts should focus
      on linkage to care among newly diagnosed persons and viral suppression among
      PWHA.

PMID- 25394191
TI  - Traumatic stress and the mediating role of alcohol use on HIV-related sexual risk
      behavior: results from a longitudinal cohort of South African women who attend
      alcohol-serving venues.
AB  - BACKGROUND: In South Africa, alcohol contributes to the HIV epidemic, in part, by
      influencing sexual behaviors. For some, high levels of alcohol consumption may be
      driven by previous traumatic experiences that result in traumatic stress. The
      purpose of this study was to quantify the longitudinal association between
      traumatic stress and unprotected sex among women who attend drinking venues and
      to assess whether this association was explained by mediation through alcohol
      use. METHODS: Data were collected in 4 waves over a year from a prospective
      cohort of 560 women who regularly attended alcohol-serving venues in a Cape Town
      township. Longitudinal mixed models examined (1) the relationship between
      traumatic stress and counts of unprotected sex and (2) whether alcohol use
      mediated the association between traumatic stress and unprotected sex. RESULTS:
      Most women reported elevated traumatic stress (80%) and hazardous alcohol use
      (88%) at least once during the study period. In models adjusted for covariates,
      traumatic stress was associated with unprotected sex (b = 0.28, SE = 0.06, t =
      4.82, P < 0.001). In addition, traumatic stress was associated with alcohol use
      (b = 0.27, SE = 0.02, t = 14.25, P < 0.001) and was also associated with
      unprotected sex (b = 0.20, SE = 0.06, t = 3.27, P < 0.01) while controlling for
      alcohol use (b = 0.28, SE = 0.07, t = 4.25, P < 0.001). The test for the mediated
      effect established that alcohol use was a significant mediator, accounting for
      27% of the total effect of traumatic stress on unprotected sex. CONCLUSIONS:
      These results highlight the need to address traumatic stress among female venue
      patrons as an important precursor of HIV risk due to alcohol use.

PMID- 25394193
TI  - The impact of transfer patients on the local cascade of HIV care continuum.
AB  - BACKGROUND: The Cascade of Care (COC) visualizes stages of HIV care progression
      within a population. It is predicated on a local population model and thus may
      not address the impact on the COC of HIV-experienced individuals diagnosed and
      cared for elsewhere who move into the area. METHODS: All individuals with a
      confirmed HIV+ test in Calgary, Canada, between January 1, 2006, and January 1,
      2013 were included. Individuals were categorized as "local" if diagnosed within
      the area, or "transfer" if diagnosed elsewhere. Subgroups were separately placed
      within the COC and then aggregated. RESULTS: Of 1019 new cases, 47% were
      transfers. Transfer patients were more likely female (35% vs. 23%; P < 0.01), non
      white (61% vs. 46%; P < 0.001), heterosexual (56% vs. 38%; P < 0.001), and have
      higher CD4 counts (400 vs. 282/mm) with undetectable viremia in 57% [63% on
      antiretroviral therapy (ART)] at baseline. Engagement was higher at every stage
      for transfer patients: 94% of transfer vs. 92% of local patients linked to HIV
      care, 90% vs. 76% (P < 0.001) were retained, 86% vs. 67% (P < 0.001) received
      ART, and at study's end, 75% vs. 58% (P < 0.001) had undetectable viremia. When
      patients were aggregated, linkage increased by 1%, retention by 6%, patient use
      of ART by 8%, and patients with viral suppression by 7%. CONCLUSIONS: The COC of
      local and transfer patients differs so significantly that both need to be
      considered separately in measuring COC, adding a previously under-recognized
      level of complexity. Use of aggregate COC without considering different levels of
      engagement could lead to imprecise information for public health initiatives and
      program metrics.

PMID- 25394194
TI  - HIV-specific ADCC improves after antiretroviral therapy and correlates with
      normalization of the NK cell phenotype.
AB  - BACKGROUND: Natural killer (NK) cell phenotype and function have recently gained
      much attention as playing crucial roles in antibody-dependent cellular
      cytotoxicity (ADCC). We investigated NK cell function, as measured by ADCC, in
      HIV-1-positive individuals before and 6 months after highly active antiretroviral
      therapy (HAART) initiation. METHOD: The ability of antibodies and NK cells to
      mediate ADCC was investigated separately and in combination in an autologous
      model. The NK cell subset distribution and NK cell phenotype (ie, expression of
      maturation and activation markers within NK cell subsets) were analyzed. RESULTS:
      The ability of NK cells to mediate ADCC was significantly increased after only 6
      months of HAART and was not explained by a normalization of NK cell subsets (CD56
      CD16 and CD56 CD16 NK cells) but rather by normalization in the frequency of NK
      cells expressing CCR7 and CD27. For individuals with no increase in ADCC after 6
      months of HAART, the frequency of NK cells expressing NKp46 was downregulated.
      The ability of antibodies to mediate ADCC alone and in combination in an
      autologous model was not improved. CONCLUSIONS: HAART improves the ability of NK
      cells to mediate ADCC after 6 months. This improvement does not correlate with
      general immune restoration, as measured by CD4 T-cell counts, but rather to a
      decrease in the frequency of NK cells expressing CCR7 and CD27.

PMID- 25394195
TI  - Intrafollicular classical Hodgkin lymphoma mimicking nodular lymphocyte
      predominant Hodgkin lymphoma: a report of two cases.
AB  - We here report on two rare cases of intrafollicular classical Hodgkin lymphoma
      (CHL). Case 1 was a 34-year-old man who underwent left supraclavicular lymph node
      biopsy. Case 2 was a 28-year-old woman who underwent surgical resection of an
      anterior mediastinal mass. The histology and microenvironment of both specimens
      resembled those of nodular lymphocyte predominant Hodgkin lymphoma. Nodular
      architecture was observed, which comprised normal-appearing small lymphocytes and
      scattered lymphocyte predominant (LP)-like cells. CD23(+) follicular dendritic
      cell meshworks were present in the nodules, surrounded by a mantle zone
      containing IgD(+) B cells. The LP-like cells were ringed by CD3(+) and PD-1(+) T
      cells, and numerous CD20(+) B cells were present in the background. However, the
      immunophenotypes of the LP-like cells resembled those of Hodgkin/Reed-Sternberg
      cells of CHL; they were positive for CD15, CD30, and PAX5, and negative for CD20,
      Bcl6, Oct2, and Bob1. These histopathological findings indicate that CHL can be
      derived from the germinal center. 

PMID- 25394196
TI  - The miR-302 cluster transcriptionally regulated by POUV, SOX and STAT5B controls
      the undifferentiated state through the post-transcriptional repression of PBX3
      and E2F7 in early chick development.
AB  - Early chick development is a systematic process governed by the concerted action
      of multiple mechanisms that regulate transcription and post-transcriptional
      processes. Post-transcriptional microRNA-mediated regulation, with regard to
      lineage specification and differentiation in early chick development, requires
      further investigation. Here, we characterize the transcriptional and post
      transcriptional regulation mechanisms in undifferentiated chick blastodermal
      cells. Expression of the miR-302 cluster, POUV, SOX2, and STAT5B decreased in a
      time-dependent manner in early chick development. We found that POUV, SOX2, and
      STAT5B regulate the transcription of the miR-302 cluster, as its 5'-flanking
      region contains binding elements for each transcription factor. Additionally,
      POUV, SOX2, and STAT5B maintain pluripotency by regulating genes containing the
      miR-302 cluster target sequence. For example, microRNAs from the miR-302 cluster
      can bind to PBX3 and E2F7 transcripts, thus acting as a post-transcriptional
      regulator that maintains the undifferentiated state of blastodermal cells by
      balancing the expression of genes related to pluripotency and differentiation.
      Based on these results, we suggest that both transcriptional and post
      transcriptional regulation of the miR302 cluster is critical for intrinsically
      controlling the undifferentiated state of chick embryonic blastodermal cells.
      These findings may help our understanding of the cellular and molecular
      mechanisms that underlie developmental decisions during early chick development.

PMID- 25394197
TI  - Using accelerometry to quantify deceleration during a high-intensity soccer
      turning manoeuvre.
AB  - Abstract The mechanics of cutting movements have been investigated extensively,
      but few studies have considered the rapid deceleration phase prior to turning
      which has been linked to muscle damage. This study used accelerometry to examine
      the influence of turning intensity on the last three steps of a severe turn. Ten
      soccer players performed 135 degrees  "V" cuts at five different intensities.
      Resultant decelerations were recorded from a trunk-mounted tri-axial
      accelerometer. Lower limb kinematics and ground reaction forces (GRF) from the
      pivot foot-ground contact (FGC) were also monitored. Average peak trunk
      decelerations were larger at the two preceding steps (4.37 +/- 0.12 g and 4.58 +/
      0.11 g) compared to the PIVOT step (4.10 +/- 0.09 g). Larger peak joint flexion
      angular velocities were observed at PRE step (ankle: 367 +/- 192 deg.s-1; knee
      493 +/- 252  deg.s-1) compared to PIVOT step (ankle 255 +/- 183 deg.s-1; knee 377
      +/- 229 deg.s-1). Turn intensity did not influence peak GRF at PIVOT step. This
      study highlights the importance of steps prior to turning and their high
      frequency loading characteristics. It is suggested that investigations of lower
      limb loading during turning should include this deceleration phase and not focus
      solely on pivot FGC.

PMID- 25394198
TI  - Frontopolar activity and connectivity support dynamic conscious augmentation of
      creative state.
AB  - No ability is more valued in the modern innovation-fueled economy than thinking
      creatively on demand, and the "thinking cap" capacity to augment state creativity
      (i.e., to try and succeed at thinking more creatively) is of broad importance for
      education and a rich mental life. Although brain-based creativity research has
      focused on static individual differences in trait creativity, less is known about
      changes in creative state within an individual. How does the brain augment state
      creativity when creative thinking is required? Can augmented creative state be
      consciously engaged and disengaged dynamically across time? Using a novel "thin
      slice" creativity paradigm in 55 fMRI participants performing verb-generation, we
      successfully cued large, conscious, short-duration increases in state creativity,
      indexed quantitatively by a measure of semantic distance derived via latent
      semantic analysis. A region of left frontopolar cortex, previously associated
      with creative integration of semantic information, exhibited increased activity
      and functional connectivity to anterior cingulate gyrus and right frontopolar
      cortex during cued augmentation of state creativity. Individual differences in
      the extent of increased activity in this region predicted individual differences
      in the extent to which participants were able to successfully augment state
      creative performance after accounting for trait creativity and intelligence.

PMID- 25394199
TI  - Pimaradienoic acid inhibits inflammatory pain: inhibition of NF-kappaB activation
      and cytokine production and activation of the NO-cyclic GMP-protein kinase G-ATP
      sensitive potassium channel signaling pathway.
AB  - Pimaradienoic acid (1) is a pimarane diterpene (ent-pimara-8(14),15-dien-19-oic
      acid) extracted at high amounts from various plants including Vigueira arenaria
      Baker. Compound 1 inhibited carrageenan-induced paw edema and acetic acid-induced
      abdominal writhing, which are its only known anti-inflammatory activities.
      Therefore, it is important to further investigate the analgesic effects of 1.
      Oral administration of 1 (1, 3, and 10 mg/kg) inhibited the acetic acid-induced
      writhing. This was also observed at 10 mg/kg via sc and ip routes. Both phases of
      the formalin- and complete Freund's adjuvant (CFA)-induced paw flinch and time
      spent licking the paw were inhibited by 1. Compound 1 inhibited carrageenan-, CFA
      , and PGE2-induced mechanical hyperalgesia. Treatment with 1 inhibited
      carrageenan-induced production of TNF-alpha, IL-1beta, IL-33, and IL-10 and
      nuclear factor kappaB activation. Pharmacological inhibitors also demonstrated
      that the analgesic effects of 1 depend on activation of the NO-cyclic GMP-protein
      kinase G-ATP-sensitive potassium channel signaling pathway. Compound 1 did not
      alter plasma levels of AST, ALT, or myeloperoxidase activity in the stomach.
      These results demonstrate that 1 causes analgesic effects associated with the
      inhibition of NF-kappaB activation, reduction of cytokine production, and
      activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel
      signaling pathway. 

PMID- 25394200
TI  - Hydroxyl-functionalized 1-(2-hydroxyethyl)-3-methyl imidazolium ionic liquids:
      thermodynamic and structural properties using molecular dynamics simulations and
      ab initio calculations.
AB  - The influences of hydroxyl functional group (-OH) on the thermodynamic and
      structural properties of ionic liquids (ILs) composed of 1-(2-Hydroxyethyl)-3
      methyl imidazolium ([C2OHmim](+)) cation and the six different conventional
      anions, including [Cl](-), [NO3](-), [BF4](-), [PF6](-), [TfO](-), and [Tf2N](-)
      have been extensively investigated using classical molecular dynamics (MD)
      simulations combined with ab initio calculations over a wide range of temperature
      (298-550 K). The volumetric thermodynamic properties, enthalpy of vaporization,
      cohesive energy density, Hildebrand solubility parameter, and heat capacity at
      constant pressure were estimated at desired temperature. The simulated densities
      were in good agreement with the experimental data with a slight overestimation.
      The interionic interaction of selected ILs was also computed using both the MD
      simulations and ab initio calculations. It was found that the highest association
      of cation and anion is attributed to [C2OHmim][Cl] followed by [C2OHmim][NO3],
      and [C2OHmim][Tf2N] with the bulkiest anion has the weakest interionic
      interaction among chosen ILs. The similar trend of interactions energies was
      nearly observed from cohesive energy density results. Additional structural
      details were comprehensively yielded by calculating radial distribution functions
      (RDFs) and spatial distribution function (SDFs) at 358 K. The most stable
      configurations of isolated and dimer ion pairs of these ILs were in excellent
      consistency with RDFs and SDFs results. Significant changes in arrangement of
      anions around the [C2OHmim](+) cation in comparison with conventional imidazolium
      based ILs can be inferred from the MD simulations and ab initio results. Also,
      microscopic structural properties disclosed that the most strong cation-cation
      interaction is ascribed to the hydroxyl-functionalized ILs composed of bulkier
      anions, whereas ILs incorporating [Cl](-) and [NO3](-) anions are mainly involved
      in cation-anion interactions. The formation of the intramolecular hydrogen
      bonding in the [C2OHmim](+) cation is another interesting result of the present
      study. 

PMID- 25394201
TI  - High ionic conductivity in a LiFeO2-LiAlO2 composite under H2/air fuel cell
      conditions.
AB  - New ionic conducting materials for electrolytes for electrochemical devices have
      been attracting the interest of researchers in energy materials. Here, for the
      first time, we report a conductive composite with high ionic conductivity derived
      from an electronic conductor alpha-LiFeO2 and an insulator gamma-LiAlO2. High
      conductivity was observed in the alpha-LiFeO2-gamma-LiAlO2 composite when
      prepared by a solid state reaction method. However, the conductivity enhancement
      in alpha-LiFeO2-gamma-LiAlO2 composite was not observed when the two oxides were
      mechanically mixed. The alpha-LiFeO2-gamma-LiAlO2 composite also exhibits O(2-)
      or/and H(+) ionic conduction which was confirmed through H2/air fuel cell
      measurements. An exceptionally high conductivity of 0.50 S cm(-1) at 650  degrees
      C was observed under H2/air fuel cell conditions. This provides a new approach to
      discover novel ionic conductors from composite materials derived from electronic
      conductors.

PMID- 25394202
TI  - Triplet state formation in homo- and heterometallic diketopyrrolopyrrole
      chromophores.
AB  - The synthesis, structural characterization, and excited-state dynamics of series
      of diketopyrrolopyrrole (DPP) bridged homodinuclear Ir(III) and heterodinuclear
      Ir(III)/Pt(II) complexes is described. Steady-state and time-resolved
      photoluminescence along with transient absorption measurements were used to probe
      the nature of the emissive and long-lived excited states. Upon excitation into
      the (1)DPP ligand-localized excited state in the presence of coordinated Ir(III)
      or Pt(II) metal centers, the intersystem crossing is enhanced, leading to a
      quenching of the (1)DPP fluorescence and the formation of the long-lived (tau ~
      30-40 MUs) (3)DPP excited state in all instances. 

PMID- 25394203
TI  - Tuning transthyretin amyloidosis inhibition properties of iododiflunisal by
      combinatorial engineering of the nonsalicylic ring substitutions.
AB  - Two series of iododiflunisal and diflunisal analogues have been obtained by using
      a two step sequential reaction solution-phase parallel synthesis. The synthesis
      combined an aqueous Suzuki-Miyaura cross-coupling and a mild electrophilic
      aromatic iodination step using a new polymer-supported iodonium version of
      Barluenga's reagent. From a selected set of 77 noniodinated and 77 iodinated
      diflunisal analogues, a subset of good transthyretin amyloid inhibitors has been
      obtained with improved turbidimetry inhibition constants, high binding affinity
      to transthyretin, and good selectivity for TTR compared to other thyroxine
      binding proteins. 

PMID- 25394205
TI  - Self-assembly of polyhedral indium-organic nanocages.
AB  - A synthetic strategy to construct discrete indium-organic polyhedra has been
      illustrated based on small three-membered windows from a 2,5
      pyridinedicarboxylate (PDC) ligand with an angle of 120 degrees .
      [Et2NH2]6[In6(PDC)12] (InOF-10) is a high-symmetry octahedron with eight three
      membered windows, and [Et2NH2]18[In18(BPDC)6(PDC)30] (InOF-11) is a complex
      polyhedron derived from 3-edge-removed octahedra with an auxiliary biphenyl-3,3'
      dicarboxylate (BPDC) ligand. Moreover, the sorption behavior of the latter is
      also well investigated. 

PMID- 25394204
TI  - Discovery of novel membrane binding structures and functions.
AB  - The function of a protein is determined by its intrinsic activity in the context
      of its subcellular distribution. Membranes localize proteins within cellular
      compartments and govern their specific activities. Discovering such membrane
      protein interactions is important for understanding biological mechanisms and
      could uncover novel sites for therapeutic intervention. We present a method for
      detecting membrane interactive proteins and their exposed residues that insert
      into lipid bilayers. Although the development process involved analysis of how
      C1b, C2, ENTH, FYVE, Gla, pleckstrin homology (PH), and PX domains bind
      membranes, the resulting membrane optimal docking area (MODA) method yields
      predictions for a given protein of known three-dimensional structures without
      referring to canonical membrane-targeting modules. This approach was tested on
      the Arf1 GTPase, ATF2 acetyltransferase, von Willebrand factor A3 domain, and
      Neisseria gonorrhoeae MsrB protein and further refined with membrane interactive
      and non-interactive FAPP1 and PKD1 pleckstrin homology domains, respectively.
      Furthermore we demonstrate how this tool can be used to discover unprecedented
      membrane binding functions as illustrated by the Bro1 domain of Alix, which was
      revealed to recognize lysobisphosphatidic acid (LBPA). Validation of novel
      membrane-protein interactions relies on other techniques such as nuclear magnetic
      resonance spectroscopy (NMR), which was used here to map the sites of micelle
      interaction. Together this indicates that genome-wide identification of known and
      novel membrane interactive proteins and sites is now feasible and provides a new
      tool for functional annotation of the proteome. 

PMID- 25394206
TI  - Nanoparticle encapsulated lipopeptide conjugate of antitubercular drug isoniazid:
      in vitro intracellular activity and in vivo efficacy in a Guinea pig model of
      tuberculosis.
AB  - Considering that Mycobacterium tuberculosis (Mtb) can survive in host phagocytes
      for decades and currently applied drugs are largely ineffective in killing
      intracellular Mtb, novel targeted delivery approaches to improve tuberculosis
      chemotherapy are urgently needed. In order to enhance the efficacy of a
      clinically used antitubercular agent (isoniazid, INH) a novel lipopeptide carrier
      was designed based on the sequence of tuftsin, which has been reported as a
      macrophage-targeting molecule. The conjugate showed relevant in vitro activity on
      Mtb H37Rv culture with low cytotoxicity and hemolytic activity on human cells.
      The conjugate directly killed intracellular Mtb and shows much greater efficacy
      than free INH. To improve bioavailability, the conjugate was encapsulated into
      poly(lactide-co-glycolide) (PLGA) nanoparticles and tested in vivo in a guinea
      pig infection model. External clinical signs, detectable mycobacterial colonies
      in the organs, and the histopathological findings substantiate the potent
      chemotherapeutic effect of orally administered conjugate-loaded nanoparticles. 

PMID- 25394207
TI  - A genome-wide association study for the incidence of persistent bovine viral
      diarrhea virus infection in cattle.
AB  - Bovine viral diarrhea viruses (BVDV) comprise a diverse group of viruses that
      cause disease in cattle. BVDV may establish both transient and persistent
      infections depending on the developmental stage of the animal at exposure. The
      objective was to determine whether genomic regions harboring single nucleotide
      polymorphisms (SNPs) could be associated with the presence or absence of
      persistent BVDV infection. A genome-wide association approach based on 777,000
      SNP markers was used. Samples of animals identified as positive (n = 1200) or
      negative (n = 1200) for the presence of BVDV in skin samples (n = 1200) were
      used. DNA samples were combined in 24 pools (100 animals per pool). One SNP,
      significant at the 5 percent genome-wide level (P = 9.41 * 10(-8) ), was detected
      on chromosome 14, located at position 80 675 176 bp. Fifteen SNPs, residing on
      chromosomes 1, 2, 6, 8, 10, 15 and 18, were moderately associated (P < 1 * 10(-5)
      ) with persistent BVDV infection. Results show that genes harboring or
      neighboring significant SNPs are involved in leucopenia, signal transduction, RNA
      splicing and DNA methylation processes.

PMID- 25394208
TI  - Coryphoid palm leaf fossils from the Maastrichtian-Danian of Central India with
      remarks on phytogeography of the Coryphoideae (Arecaceae).
AB  - PREMISE OF RESEARCH: A large number of fossil coryphoid palm wood and fruits have
      been reported from the Deccan Intertrappean beds of India. We document the oldest
      well-preserved and very rare costapalmate palm leaves and inflorescence like
      structures from the same horizon. METHODOLOGY: A number of specimens were
      collected from Maastrichtian-Danian sediments of the Deccan Intertrappean beds,
      Ghughua, near Umaria, Dindori District, Madhya Pradesh, India. The specimens are
      compared with modern and fossil taxa of the family Arecaceae. PIVOTAL RESULTS:
      Sabalites dindoriensis sp. nov. is described based on fossil leaf specimens
      including basal to apical parts. These are the oldest coryphoid fossil palm
      leaves from India as well as, at the time of deposition, from the Gondwana-
      derived continents. CONCLUSIONS: The fossil record of coryphoid palm leaves
      presented here and reported from the Eurasian localities suggests that this is
      the oldest record of coryphoid palm leaves from India and also from the Gondwana-
      derived continents suggesting that the coryphoid palms were well established and
      wide spread on both northern and southern hemispheres by the Maastrichtian
      Danian. The coryphoid palms probably dispersed into India from Europe via Africa
      during the latest Cretaceous long before the Indian Plate collided with the
      Eurasian Plate.

PMID- 25394209
TI  - Anti-SSA antibodies are present in immunoglobulin preparations.
AB  - BACKGROUND: Anti-SSA autoantibodies are among the most frequently detected
      autoantibodies and have traditionally been associated with Sjogren's syndrome
      (SjS) and systemic lupus erythematosus. The unexpected finding of anti-SSA
      antibodies in a patient with common variable immunodeficiency disorder (CVID)
      treated with intravenous immunoglobulin (IVIG), who developed discoid lupus
      erythematosus, prompted us to investigate the presence of anti-SSA antibodies in
      IVIG preparations. Since anti-SSA antibodies may be present in apparently healthy
      individuals without overt autoimmune features, IVIG preparations may also contain
      anti-SSA antibodies. STUDY DESIGN AND METHODS: IVIG consists of polyclonal
      immunoglobulin G isolated from the plasma of more than 1000 blood donors. Several
      IVIG batches from different suppliers and serum samples of patients receiving
      these IVIG products were tested for the presence of anti-nuclear antibodies
      (ANAs) and extractable nuclear antibodies (ENAs). In addition, we tested several
      plasma pools for the presence of anti-SSA and subsequent serum samples of
      individual donors. RESULTS: Several CVID-patients receiving IVIG tested positive
      for ANA and anti-SSA. The IVIG products administered also contained clearly
      detectable concentrations of these antibodies. The frequency of apparently
      healthy blood donors with anti-SSA positivity was 0.69% and one of 1894 donors
      (0.05%) showed a very high titer of anti-SSA of more than 10,000 U/mL.
      CONCLUSION: Anti-SSA is present in IVIG products and in blood donors without
      clinical symptoms. IVIG replacement can interfere with ANA and ENA serology by
      passive transfer of autoantibodies. We hypothesize that such autoantibodies may
      be causally related to disease manifestations in some recipients.

PMID- 25394210
TI  - Comparison of bone mineral density changes in pediatric thalassemic patients with
      and without hematopoietic stem cell transplant.
AB  - OBJECTIVES: Beta thalassemia major is a genetic hemoglobin disorder that affects
      bone density. The disease leads to deteriorating bone structure but can be
      treated with hematopoietic stem cell transplant. We aimed to assess bone mineral
      density changes in pediatric beta thalassemia major patients who had undergone a
      hematopoietic stem cell transplant compared with similarly affected patients who
      had not undergone a hematopoietic stem cell transplant. MATERIALS AND METHODS:
      Forty beta thalassemia major patients, 20 transplant and 20 nontransplant,
      younger than 16 years of age were enrolled. The mean age of transplant patients
      was 8.15 years and nontransplant patients was 9.5 years (P = .242). The
      female:male ratio was 1:1 in both groups. None of the patients reached puberty
      during this study. Bone mineral density was evaluated in transplant patients
      before and 1 year after hematopoietic stem cell transplant. Bone mineral density
      of nontransplant patients also was evaluated 1 year after their initial bone
      mineral density test. A Norland XR-46 densitometer was used to make all bone
      mineral density measurements. None of the patients had a z score < -2. RESULTS:
      Mean bone mineral density changes in the femur and spine during this study were
      0.008 +/- 0.075 g/cm2 and 0.048 +/- 0.045 g/cm2 in transplant patients and 0.045
      +/- 0.072 g/cm2 and 0.036 +/- 0.058 g/cm2 in nontransplant patients. No
      significant differences between bone mineral density changes in transplant and
      nontransplant patients were detected during the study. CONCLUSIONS: No
      significant effects on bone mineral density were detected in hematopoietic stem
      cell transplant pediatric beta thalassemia major patients compared with similarly
      affected nontransplant patients. Studies of longer duration may be required to
      identify significant changes in bone mineral density in hematopoietic stem cell
      transplant patients.

PMID- 25394211
TI  - A population model of early rheumatoid arthritis disease activity during
      treatment with methotrexate, sulfasalazine and hydroxychloroquine.
AB  - AIMS: To develop a population model describing the disease activity (DAS28) time
      course in patients with early rheumatoid arthritis (RA) treated with triple
      disease-modifying anti-rheumatic drug (DMARD) therapy (methotrexate,
      sulfasalazine and hydroxychloroquine). METHODS: DAS28 was obtained in 263
      patients with early RA from initiation of therapy until 60 weeks. Using
      NONMEM((r)), base models (DAS28 vs. time) and covariate influences were
      investigated for the population. RESULTS: The best model was an exponential model
      of DAS28 vs. time that was additive to baseline DAS28, with covariance between
      parameters, and a combined residual error model. Age and patient smoking history
      were covariates significantly affecting response to therapy. Population estimates
      were baseline DAS28 (5.7), extent of change in DAS28 (-2.8) and the half-life of
      disease activity (6.2 weeks; time to steady disease state achieved within
      approximately 30 weeks). Older individuals exhibited more severe baseline DAS28,
      described by a power function centred around 57 years (baseline DAS28 for 40- and
      70-year-old patients were 5.4 vs. 5.8, respectively) and current smokers took
      longer to achieve a steady disease state (approximately 50 weeks). There was
      considerable within-patient random variability in DAS28 over time (empirical 90%
      CI for DAS28 in a population typical patient at 60 weeks: 1.8, 4.2 with median
      value of 2.8). CONCLUSIONS: This is the first report of a disease activity model
      for early RA treated with triple DMARD therapy. Smoking and age were identified
      as covariates.

PMID- 25394212
TI  - Use of infliximab in toxic epidermal necrolysis: a still opened challenge.
AB  - Toxic epidermal necrolysis (TEN), also known as Lyell syndrome, is a potential
      life-threatening muco-cutaneous disease with important systemic implications. It
      affects the skin and mucous membranes, with involvement of more than 30% of body
      surface and it is mostly caused by drugs. Although the pathogenesis is not fully
      elucidated, it is probably linked to the inability to detoxicate reactive
      metabolites of drugs, to genetic susceptibility and to immune factors leading to
      cellular apoptosis. Currently, there are no randomized control trials and
      stardardized therapeutical approaches for the management of Lyell syndrome;
      therefore controversial clinical responses to the most common used drug in TEN
      make it difficult for the clinical-therapeutic approach. The authors reported
      their experience on three patients affected by Lyell syndrome treated with
      infliximab. 

PMID- 25394213
TI  - The intraday reliability of the Reactive Strength Index calculated from a drop
      jump in professional men's basketball.
AB  - PURPOSE: To evaluate the reliability of the Reactive Strength Index (RSI) and
      jump-height (JH) performance from multiple drop heights in an elite population.
      METHODS: Thirteen professional basketball players (mean+/-SD age 25.8+/-3.5 y,
      height 1.96+/-0.07 m, mass 94.8+/-8.2 kg) completed 3 maximal drop-jump attempts
      onto a jump mat at 4 randomly assigned box heights and 3 countermovement-jump
      trials. RESULTS: No statistical difference was observed between 3 trials for both
      the RSI and JH variable at all the tested drop heights. The RSI for drop-jump
      heights from 20 cm resulted in a coefficient of variation (CV)=3.1% and an
      intraclass correlation (ICC alpha)=.96, 40 cm resulted in a CV=3.0% and an ICC
      alpha=.95, and 50 cm resulted in a CV=2.1% and an ICC alpha=.99. The JH variable
      at the 40-cm drop-jump height resulted in the highest reliability CV=2.8% and an
      ICC alpha=.98. CONCLUSION: When assessing the RSI the 20-, 40-, and 50-cm drop
      heights are recommended with this population. When assessing large groups it
      appears that only 1 trial is required when assessing the RSI variable from the
      20, 40-, and 50-cm drop heights.

PMID- 25394214
TI  - Introduction to 'gums and joints' special issue. Introduction.

PMID- 25394215
TI  - Nonalcoholic steatohepatits and liver steatosis modify partial hepatectomy
      recovery.
AB  - BACKGROUND: The impact of nonalcoholic fatty liver disease (NAFLD) comprising
      simple steatosis (NAFL) and steatohepatitis (NASH) on liver recovery after
      partial hepatectomy has not been evaluated. This pilot study investigated whether
      there is an effect of proven NAFLD on liver recovery. METHODS: Thirty-one
      patients elected for partial hepatectomy were characterized and included into a
      prospective study. Liver samples were staged according to the NAFLD activity
      score. Liver function was measured by using the LiMAx method on postoperative
      days (POD) 1, 3, 5, and 10. RESULTS: Nineteen patients were identified to suffer
      from NAFLD (NAFL, n = 11; NASH, n = 8). In NAFL, preoperative liver function (p =
      .48) and hepatic recovery on POD 1, 3, and 5 was comparable to controls (p > .05,
      respectively), while it was impaired on POD 10 (p = .022). NASH patients had
      preoperative enzymatic function comparable to controls (p = .10), but there was a
      trend to reduced levels on POD 1 (p = .082) and 5 (p = .062), which became
      significant on POD 10 (p = .003). CONCLUSION: This study suggests that NAFLD
      impairs functional recovery assessed by LiMAx after partial hepatectomy.

PMID- 25394216
TI  - Laparoscopic endoscopic cooperative surgery.
AB  - Laparoscopic and endoscopic cooperative surgery (LECS) is a newly developed
      concept for tumor dissection of the gastrointestinal tract that was first
      investigated for local resection of gastric gastrointestinal stromal tumors
      (GIST). The first reported version of LECS for GIST has been named 'classical
      LECS' to distinguish it from other modified LECS procedures, such as inverted
      LECS, a combination of laparoscopic and endoscopic approaches to neoplasia with a
      non-exposure technique (CLEAN-NET), and non-exposed endoscopic wall-inversion
      surgery (NEWS). These modified LECS procedures were developed for dissection of
      malignant tumors which may seed tumor cells into the abdominal cavity. While
      these LECS-related procedures might prevent tumor seeding, their application is
      limited by several factors, such as tumor size, location and technical
      difficulty. Currently, classical LECS is a safe and useful procedure for gastric
      submucosal tumors without mucosal defects, independent of tumor location, such as
      proximity to the esophagogastric junction or pyloric ring. For future
      applications of LECS-related procedures for other malignant diseases with mucosal
      lesions such as GIST with mucosal defects and gastric cancer, some improvements
      in the techniques are needed. 

PMID- 25394218
TI  - Vitamin D status and its predictors among pre-school children in Adelaide.
AB  - AIM: To assess vitamin D status and its predictors in a representative population
      sample of pre-school children in Adelaide (latitude of 35 degrees S). METHODS:
      Cross-sectional survey of children aged between 1 and 5 years from areas of low,
      medium and high socio-economic status as identified from the 2001 Census data,
      Australian Bureau of Statistics. Children were recruited between September 2005
      and July 2007 using a door knocking protocol based on a stratified sampling
      method to obtain a representative sample of this age group. Serum 25
      hydroxyvitamin D (25(OH)D) was determined using a radio-immunoassay kit. Vitamin
      D deficiency was defined as serum 25(OH)D) <30 nmol/L and insufficiency defined
      as serum 25(OH)D >=30 and <50 nmol/L according to the Institute of Medicine.
      RESULTS: Fifty-two per cent of eligible children took part in the study. Mean
      (standard deviation) serum 25(OH)D was 73 (26) nmol/L (n = 221). The prevalence
      of vitamin D deficiency and insufficiency was 4% and 16%, respectively, with the
      prevalence being higher in winter (8% and 22%, respectively). Season of the year
      of blood collection and mother being born in Australia were significant
      predictors of serum 25(OH)D concentration, but age, sex, socio-economic status,
      BMI category or dietary supplement use were not related to vitamin D status.
      CONCLUSIONS: Vitamin D status of this representative sample of pre-school
      children in Australia is adequate, and the prevalence of vitamin D deficiency is
      low based on the Institute of Medicine criteria.

PMID- 25394217
TI  - The association between the use of proton pump inhibitors and the risk of
      hypomagnesemia: a systematic review and meta-analysis.
AB  - BACKGROUND: Although many case reports have described patients with proton pump
      inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia
      has not been fully clarified through comparative studies. We aimed to evaluate
      the association between the use of PPI and the risk of developing hypomagnesemia
      by conducting a systematic review with meta-analysis. METHODS: We conducted a
      systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary
      keywords "proton pump," "dexlansoprazole," "esomeprazole," "ilaprazole,"
      "lansoprazole," "omeprazole," "pantoprazole," "rabeprazole," "hypomagnesemia,"
      "hypomagnesaemia," and "magnesium." Studies were included if they evaluated the
      association between PPI use and hypomagnesemia and reported relative risks or
      odds ratios or provided data for their estimation. Pooled odds ratios with 95%
      confidence intervals were calculated using the random effects model. Statistical
      heterogeneity was assessed with Cochran's Q test and I2 statistics. RESULTS: Nine
      studies including 115,455 patients were analyzed. The median Newcastle-Ottawa
      quality score for the included studies was seven (range, 6-9). Among patients
      taking PPIs, the median proportion of patients with hypomagnesemia was 27.1%
      (range, 11.3-55.2%) across all included studies. Among patients not taking PPIs,
      the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3
      52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775
      (95% confidence interval 1.077-2.924). Significant heterogeneity was identified
      using Cochran's Q test (df = 7, P<0.001, I2 = 98.0%). CONCLUSIONS: PPI use may
      increase the risk of hypomagnesemia. However, significant heterogeneity among the
      included studies prevented us from reaching a definitive conclusion.

PMID- 25394219
TI  - A new species of sucking louse (Phthiraptera: Anoplura: Linognathidae) from
      Gunther's Dikdik (Madoqua guentheri) in Kenya.
AB  - Linognathus samburi n. sp. is described from adult male and female specimens
      collected from a juvenile female Gunther's dikdik (Madoqua guentheri) live
      trapped near Olturot Village, Samburu district (Rift Valley Province) in northern
      Kenya. The new species is distinguished from other species of Linognathus
      including Linognathus geigyi and Linognathus damarensis, both of which parasitize
      Kirk's dikdik (Madoqua kirkii). A dichotomous key to the species of Linognathus
      that are known to parasitize dikdiks is included.

PMID- 25394220
TI  - Lowering targets for hemoglobin A1c in children with type 1 diabetes: raising the
      bar.

PMID- 25394222
TI  - Chloromethane release from carbonaceous meteorite affords new insight into Mars
      lander findings.
AB  - Controversy continues as to whether chloromethane (CH3Cl) detected during
      pyrolysis of Martian soils by the Viking and Curiosity Mars landers is indicative
      of organic matter indigenous to Mars. Here we demonstrate CH3Cl release (up to 8
      MUg/g) during low temperature (150-400 degrees C) pyrolysis of the carbonaceous
      chondrite Murchison with chloride or perchlorate as chlorine source and confirm
      unequivocally by stable isotope analysis the extraterrestrial origin of the
      methyl group (delta(2)H +800 to +11000/00, delta(13)C -19.2 to +100/00,). In the
      terrestrial environment CH3Cl released during pyrolysis of organic matter derives
      from the methoxyl pool. The methoxyl pool in Murchison is consistent both in
      magnitude (0.044%) and isotope signature (delta(2)H +1054 +/- 6260/00, delta(13)C
      +43.2 +/- 38.80/00,) with that of the CH3Cl released on pyrolysis. Thus CH3Cl
      emissions recorded by Mars lander experiments may be attributed to methoxyl
      groups in undegraded organic matter in meteoritic debris reaching the Martian
      surface being converted to CH3Cl with perchlorate or chloride in Martian soil.
      However we cannot discount emissions arising additionally from organic matter of
      indigenous origin. The stable isotope signatures of CH3Cl detected on Mars could
      potentially be utilized to determine its origin by distinguishing between
      terrestrial contamination, meteoritic infall and indigenous Martian sources. 

PMID- 25394223
TI  - Irregular narrowing of the main pancreatic duct in association with a wall
      thickening is a key sign at endoscopic ultrasonography for the diagnosis of
      autoimmune pancreatitis.
AB  - OBJECTIVES: The aim of this study was to assess the accuracy of key signs
      identified at endoscopic ultrasonography in diagnosing an autoimmune pancreatitis
      (AIP). METHODS: Between January 2007 and December 2011, a retrospective case
      control study was conducted in 177 patients with AIP (n = 30), pancreatic
      adenocarcinoma (n = 42), pancreatic neuroendocrine tumor (n = 21), alcoholic
      chronic pancreatitis (n = 32), and symptomatic common bile duct stones (n = 52).
      RESULTS: An irregular narrowing of the main pancreatic duct in association with a
      wall thickening was seen in 28 of 30 AIP, 1 of 42 pancreatic adenocarcinoma, 0 of
      21 pancreatic neuroendocrine tumor, 0 of 32 alcoholic chronic pancreatitis, and 0
      of 52 common bile duct stones (P < 0.05). Sensitivity, specificity, positive and
      negative predictive values, and overall diagnostic accuracy of this sign for the
      diagnosis of AIP were 93%, 99.3%, 96.3%, 98.6%, and 98.3%, respectively. In type
      1 AIP, hyperechoic parietal thickening was more frequent (92.3% vs 33.3%, P <
      0.05). In type 2 AIP, hypoechoic parietal thickening was more frequent (83.3% vs
      23.1%, P < 0.05). CONCLUSIONS: An irregular narrowing of the main pancreatic duct
      in association with a wall thickening seen at endoscopic ultrasonography is
      accurate in diagnosing AIP. The type of echogenicity of the thickening is well
      correlated with the type of AIP.

PMID- 25394221
TI  - Dimethyloxalylglycine prevents bone loss in ovariectomized C57BL/6J mice through
      enhanced angiogenesis and osteogenesis.
AB  - Hypoxia-inducible factor 1-alpha (HIF-1alpha) plays a critical role in
      angiogenesis-osteogenesis coupling during bone development and bone regeneration.
      Previous studies have shown that 17beta-estradiol activates the HIF-1alpha
      signaling pathway and that mice with conditional activation of the HIF-1alpha
      signaling pathway in osteoblasts are protected from ovariectomy (OVX)-induced
      bone loss. In addition, it has been shown that hypoxia facilitates the osteogenic
      differentiation of mesenchymal stem cells (MSCs) and modulates Wnt/beta-catenin
      signaling. Therefore, we hypothesized that activation of the HIF-1alpha signaling
      pathway by hypoxia-mimicking agents would prevent bone loss due to estrogen
      deficiency. In this study, we confirmed the effect of dimethyloxalylglycine
      (DMOG), a hypoxia-mimicking agent, on the HIF-1alpha signaling pathway and
      investigated the effect of DMOG on MSC osteogenic differentiation and the
      Wnt/beta-catenin signaling pathway. We then investigated the effect of DMOG
      treatment on OVX-induced bone loss. Female C57BL/6J mice were divided into sham,
      OVX, OVX+L-DMOG (5 mg/kg/day), and OVX+H-DMOG (20 mg/kg/day) groups. At
      sacrifice, static and dynamic bone histomorphometry were performed with micro
      computed tomography (micro-CT) and undecalcified sections, respectively. Bone
      strength was assessed with the three-point bending test, and femur vessels were
      reconstructed and analyzed by micro-CT. Serum vascular endothelial growth factor
      (VEGF), osteocalcin, and C-terminal telopeptides of collagen type(CTX) were
      measured by ELISA. Tartrate-resistant acid phosphatase staining was used to
      assess osteoclast formation. Alterations in the HIF-1alpha and Wnt/beta-catenin
      signaling pathways in the bone were detected by western blot. Our results showed
      that DMOG activated the HIF-1alpha signaling pathway, which further activated the
      Wnt/beta-catenin signaling pathway and enhanced MSC osteogenic differentiation.
      The micro-CT results showed that DMOG treatment improved trabecular bone density
      and restored the bone microarchitecture and blood vessels in OVX mice. Bone
      strength was also partly restored in DMOG-treated OVX mice. Dynamic bone
      histomorphometric analysis of the femur metaphysic revealed that DMOG increased
      the mineralizing surface, mineral apposition rate, and bone formation rate. The
      serum levels of VEGF and osteocalcin were higher in DMOG-treated OVX mice.
      However, there were no significant differences in serum CTX or in the number of
      tartrate-resistant acid phosphatase-stained cells between DMOG-treated OVX mice
      and OVX mice. Western blot results showed that DMOG administration partly rescued
      the decrease in HIF-1alpha and beta-catenin expression following ovariectomy.
      Collectively, these results indicate that DMOG prevents bone loss due to
      ovariectomy in C57BL/6J mice by enhancing angiogenesis and osteogenesis, which
      are associated with activated HIF-1alpha and Wnt/beta-catenin signaling pathways.

PMID- 25394224
TI  - Possible conduit-matrix water exchange signatures outlined at a karst spring.
AB  - During a significant flood event, reversible water exchanges may occur between a
      karst conduit and its adjacent porous rock (frequently designated as "matrix"):
      while the flood pulse rises, some conduit-derived water is forced into the
      matrix; then, as the flood recedes, the same water flows back into the stream
      passage. The present note addresses such a karst setting in the Carpathian
      Mountains (Romania), where in addition, a usually stable flux of chloride
      originating in a natural saline inflow, was being mixed with a variable flow of
      karst freshwater. For that particular case, with the above-mentioned process of
      matrix storage/release from storage assumedly taking place downstream of the
      mixing site, two distinct chemical signatures could be noticed during a flood
      event: an initial depletion in the spring flow chloride flux, subsequently
      followed by a comparable chloride flux enrichment (the depletion and the
      enrichment being outlined with respect to the essentially stable chloride flux
      value that had been noticed to persist at the spring over a long period of flow
      rate recession). Concomitantly with such flood-induced fluctuations in the spring
      chloride flux, the spring discharge displayed, for long periods, abnormally slow
      variations: the latter likely indicated that the spring supply rate actual
      oscillations were buffered by the reversible water exchanges which took place
      between the karst conduit and its adjacent matrix. On the whole, these results
      show that conduit-matrix water exchanges could be interpreted by simple mass
      balance calculations that involved fluxes of a conservative tracer (the chloride
      ion in that particular case). 

PMID- 25394225
TI  - Cognitive outcome varies in adolescents born preterm, depending on gestational
      age, intrauterine growth and neonatal complications.
AB  - AIM: The aim of this study was to investigate long-term cognitive outcome in a
      cohort of 18-year-olds born preterm and previously assessed at the age of 5.5.
      METHODS: We tested 134 adolescents born preterm with a very low birthweight of
      <1500 g and 94 term-born controls with a comprehensive cognitive battery at 18
      years of age. The cohort was subdivided into 73 extremely preterm, 42 very
      preterm and 19 moderately preterm infants with gestational ages of 23-27, 28-31
      and 32-36 weeks, respectively. The moderately preterm group was dominated by
      adolescents born small for gestational age. RESULTS: Very preterm adolescents
      performed on a par with term-born controls. In contrast, extremely preterm
      adolescents displayed inferior results on all cognitive tests, more so if they
      had suffered neonatal complications. Moderately preterm adolescents scored lower
      than very preterm and full-term born adolescents, particularly on complex
      cognitive tasks. CONCLUSION: Adolescents born at 28 weeks of gestation or later,
      with appropriate birthweight and no perinatal complications, functioned like term
      born peers at 18 years of age. Extremely preterm birth per se posed a risk for
      long-term cognitive deficits, particularly executive deficits. Adolescents born
      moderately preterm but small for gestational age were at risk of general
      cognitive deficits.

PMID- 25394226
TI  - Current and future directions in clinical fatigue management: An update for
      emergency medicine practitioners.
AB  - Physicians worldwide are working round the clock to meet the demands of
      healthcare systems, especially in acute medical settings such as EDs. Demanding
      shift work schedules cause fatigue and thus deterioration in mood and motor
      performance. This article explores the effects of sleep deprivation, focusing on
      cognition, executive decision-making and the implications for clinical care.
      Humans are capable of functioning and even adapting to sleep restriction;
      however, clinicians should be aware of pitfalls and absolute minimums for sleep.
      Fatigue management training shows promise in enhancing safety in aviation and
      might have a role in medical shift work. Strategic napping improves performance
      during night shift in the ED, but does not fully negate fatigue. Drugs offer
      limited benefit for performance under sleep-deprived conditions, and whenever
      possible, sleep and/or strategic napping takes precedence. 

PMID- 25394227
TI  - Continuous flow synthesis of chiral amines in organic solvents: immobilization of
      E. coli cells containing both omega-transaminase and PLP.
AB  - E. coli cells containing overexpressed (R)-selective omega-transaminase and the
      cofactor PLP were immobilized on methacrylate beads suitable for continuous flow
      applications. The use of an organic solvent suppresses leaching of PLP from the
      cells; no additional cofactor was required after setting up the packed-bed
      reactor containing the biocatalyst (omega-TA-PLP). Non-natural ketone substrates
      were transformed in flow with excellent enantioselectivity (>99% ee). Features of
      this novel system include high-throughput (30-60 min residence time), clean
      production (no quench, workup, or purification required), high enzyme stability
      (the packed-bed reactor can be continuously operated for 1-10 days), and
      excellent mass recovery. 

PMID- 25394228
TI  - Friction of water on graphene and hexagonal boron nitride from ab initio methods:
      very different slippage despite very similar interface structures.
AB  - Friction is one of the main sources of dissipation at liquid water/solid
      interfaces. Despite recent progress, a detailed understanding of water/solid
      friction in connection with the structure and energetics of the solid surface is
      lacking. Here, we show for the first time that ab initio molecular dynamics can
      be used to unravel the connection between the structure of nanoscale water and
      friction for liquid water in contact with graphene and with hexagonal boron
      nitride. We find that although the interface presents a very similar structure
      between the two sheets, the friction coefficient on boron nitride is ~ 3 times
      larger than that on graphene. This comes about because of the greater corrugation
      of the energy landscape on boron nitride arising from specific electronic
      structure effects. We discuss how a subtle dependence of the friction on the
      atomistic details of a surface, which is not related to its wetting properties,
      may have a significant impact on the transport of water at the nanoscale, with
      implications for the development of membranes for desalination and for osmotic
      power harvesting.

PMID- 25394229
TI  - Effect of rooibos (Aspalathus linearis) on growth control of Clostridium
      perfringens and lipid oxidation of ready-to-eat Jokbal (pig's trotters).
AB  - This study investigated the antimicrobial effects of rooibos (tea extract),
      potassium lactate (PL) and sodium diacetate (SDA) mixture alone or in
      combinations on the growth of Clostridium perfringens vegetative cell and spore
      in ready-to-eat (RTE) Jokbal (pig's trotters). Addition of a combination of 10%
      rooibos and 4% PL + SDA inhibit growth of C. perfringens vegetative cell in
      Jokbal at 24  degrees C and 36  degrees C. The significant inhibition on
      germination and growth of C. perfringens spores was also observed in Jokbal with
      a combination of 10% rooibos and 4% PL + SDA (PL: 2.24%, SDA: 0.16%) at 24 
      degrees C. The Jokbal treated with 10% rooibos and 4% PL + SDA mixture had
      significantly (P < 0.05) lower TBARS values than the control at 10 and 24 
      degrees C. The lipid oxidation inhibition effect was the highest (P < 0.05) in
      anaerobic packed Jokbal with 10% rooibos. The addition of a combination of 10%
      rooibos and 4% PL + SDA during the processing of Jokbal prevented the growth of
      C. perfringens and the germination and growth of C. perfringens spores at room
      temperature. This study shows rooibos tea as a valuable natural food preservative
      in meat products. 

PMID- 25394230
TI  - An open tubular ion chromatograph.
AB  - We describe an open tubular ion chromatograph (OTIC) that uses anion exchange
      latex coated 5 MUm radius silica and 9.8 MUm radius poly(methyl methacrylate)
      tubes and automated time/pressure based hydrodynamic injection for pL-nL scale
      injections. It is routinely possible to generate 50,000 plates or more (up to
      150,000 plates/m, columns between 0.3 and 0.8 m have been used), and as such,
      fast separations are possible, comparable to or in some cases better than the
      current practice of IC. With an optimized admittance detector, nonsuppressed
      detection permits LODs of submicromolar to double digit micromolar for a variety
      of analytes. However, large volume injections are possible and can significantly
      improve on this. A variety of eluents, the use of organic modifiers, and
      variations of eluent pH can be used to tailor a given separation. The approach is
      discussed in the context of extraterrestrial exploration, especially Mars, where
      the existence of large amounts of perchlorate in the soil needs to be confirmed.
      These columns can survive drying and freezing, and small footprint, low power
      consumption, and simplicity make OTIC a good candidate for such a mission.

PMID- 25394231
TI  - Is combination therapy for resistant vitreous seeds really essential? - reply.

PMID- 25394232
TI  - Recent developments in colorectal imaging.
AB  - PURPOSE OF REVIEW: The aim of this review is to provide an update on important
      recent advances in radiologic colorectal imaging, with emphasis on detection,
      staging, and surveillance of colorectal neoplasia. RECENT FINDINGS: Colorectal
      imaging advances with magnetic resonance (MR), computed tomography colonography
      (CTC), and positron emission tomography (PET) over the past year or so have been
      substantial. Progress in MRI for rectal cancer was most notable in terms of
      assessment of response to neoadjuvant therapy. Continued maturation and clinical
      validation of CTC was observed for the evaluation of advanced neoplasia, among
      other areas. Multimodality approaches to colorectal imaging that incorporate
      functional PET data have also made impressive strides forward. SUMMARY: Recent
      advances in cross-sectional and functional radiologic imaging of the colorectum
      will positively impact the clinical capabilities for noninvasive evaluation of
      colorectal neoplasia.

PMID- 25394233
TI  - The intestinal protozoa: emerging impact on global health and development.
AB  - PURPOSE OF REVIEW: To highlight new findings on the relevance of gastrointestinal
      protozoan infections to global public health in low-income and middle-income
      countries and suggest new large-scale interventions. RECENT FINDINGS: New disease
      burden assessments and epidemiological studies highlight the role of the major
      intestinal protozoa as important etiologic disease agents in low-income and
      middle-income countries. Despite their prevalence and adverse health impact, such
      information has not yet translated to the implementation of large-scale
      interventions as exist for helminth infections and other neglected tropical
      diseases. There are also several key research and development questions that must
      be addressed for intestinal protozoan infections and the potential need for new
      tools, for example, drugs, diagnostics, and vaccines. Additional studies have
      identified new and emerging species of intestinal protozoa relevant to global
      public health such as Dientamoeba fragilis and Blastocystis hominis and how they
      too might emerge as important gastrointestinal pathogens in the coming years.
      SUMMARY: New and emerging information on intestinal protozoa are reviewed with
      emphasis on aspects considered relevant to global health policymakers including
      prospects for scaling up interventions against intestinal protozoan infections in
      resource-poor countries.

PMID- 25394234
TI  - Constipation: pathophysiology and management.
AB  - PURPOSE OF REVIEW: Continuing advances in pharmaceutical development are
      providing an expanding array of treatment approaches for patients with chronic
      constipation. More comprehensive characterization of pancolonic motility carries
      the promise of improved understanding of the pathophysiology of this common
      disorder. Chronic constipation which responds poorly to laxatives may result from
      the use of drugs such as opioids, or from defecation disorders and advanced
      colonic dysmotility. RECENT FINDINGS: This article highlights improved
      characterization of pancolonic motility, evidence of efficacy of established and
      novel drugs for both idiopathic and opioid-induced constipation and a new
      algorithm for the evaluation of patients with chronic idiopathic constipation who
      respond inadequately to available laxatives. SUMMARY: The articles cited in this
      review inform the reader of new developments in the evaluation and treatment of
      patients with chronic constipation.

PMID- 25394235
TI  - The molecular basis of Clostridium difficile disease and host response.
AB  - PURPOSE OF REVIEW: Clostridium difficile infection (CDI) ranges from asymptomatic
      colonization to severe colitis and death. The physiologic and molecular
      mechanisms determining disease outcome are thus far poorly understood. Here, we
      review recent advances in the relationship between host response to infection and
      disease outcome. Furthermore, we review recent studies on the relationship
      between intestinal microbial ecology and pathogenesis of CDI. RECENT FINDINGS:
      Severe CDI is characterized by toxin-induced epithelial injury and marked
      intestinal inflammation. Recent studies demonstrate that systemic markers of
      inflammation correlate with disease outcome. Peripheral neutrophil count, C
      reactive protein, and proinflammatory cytokines are elevated in patients with
      severe disease as compared with asymptomatic controls. Furthermore, fecal
      inflammatory biomarkers are better predictors of disease severity and diarrhea
      persistence than C. difficile abundance. A landmark study reported higher than
      80% success rate of fecal microbiota transplantation for treatment of recurrent
      CDI. The commensal microbes responsible for C. difficile protection, and the
      molecular basis by which microbial ecology impacts disease outcome, are under
      active investigation. SUMMARY: Under conditions of altered microbial ecology, C.
      difficile incites epithelial injury and marked intestinal inflammation, the
      primary determinant of disease outcome. Restoration of a diverse intestinal
      microbial population by fecal microbiota transplantation attenuates disease and
      prevents recurrence by mechanisms that are yet to be fully elucidated.

PMID- 25394236
TI  - The gut microbiome in health and in disease.
AB  - PURPOSE OF REVIEW: Recent technological advancements and expanded efforts have
      led to a tremendous growth in the collective knowledge of the human microbiome.
      This review will highlight some of the important recent findings in this area of
      research. RECENT FINDINGS: Studies have described the structure and functional
      capacity of the bacterial microbiome in the healthy state and in a variety of
      disease states. Downstream analyses of the functional interactions between the
      host and its microbiome are starting to provide mechanistic insights into these
      interactions. These data are anticipated to lead to new opportunities for
      diagnosis, prognosis, and treatment of a variety of human diseases. SUMMARY:
      There is a fast growing collection of data describing the structure and
      functional capacity of the microbiome in a variety of conditions available to the
      research community for consideration and further exploration. Ongoing efforts to
      further characterize the functions of the microbiome and the mechanisms
      underlying host-microbe interactions will provide a better understanding of the
      role of the microbiome in health and disease.

PMID- 25394237
TI  - Update on molecular epidemiology of Shigella infection.
AB  - PURPOSE OF REVIEW: Shigella spp. are important etiologic agents of diarrhea
      worldwide. This review summarizes the recent findings on the epidemiology,
      diagnosis, virulence genes, and pathobiology of Shigella infection. RECENT
      FINDINGS: Shigella flexneri and Shigella sonnei have been identified as the main
      serogroups circulating in developing and developed countries, respectively.
      However, a shift in the dominant species from S. flexneri to S. sonnei has been
      observed in countries that have experienced recent improvements in socioeconomic
      conditions. Despite the increasing usage of molecular methods in the diagnosis
      and virulence characterization of Shigella strains, researchers have been
      unsuccessful in finding a specific target gene for this bacillus. New research
      has demonstrated the role of proteins whose expressions are temperature
      regulated, as well as genes involved in the processes of adhesion, invasion,
      dissemination, and inflammation, aiding in the clarification of the complex
      pathobiology of shigellosis. SUMMARY: Knowledge about the epidemiologic profile
      of circulating serogroups of Shigella and an understanding of its pathobiology as
      well as of the virulence genes is important for the development of preventive
      measures and interventions to reduce the worldwide spread of shigellosis.

PMID- 25394239
TI  - Fluorofenidone attenuates TGF-beta1-induced lung fibroblast activation via
      restoring the expression of caveolin-1.
AB  - Caveolin-1 plays an important role in the pathogenesis of idiopathic pulmonary
      fibrosis. We previously showed that fluorofenidone (FD), a novel pyridine agent,
      can attenuate bleomycin-induced experimental pulmonary fibrosis and restore the
      production of caveolin-1. In this study, we explore mainly whether caveolin-1
      plays a critical role in the anti-pulmonary fibrosis effects of FD in vitro. The
      normal human lung fibroblasts (NHLFs) were cultured with transforming growth
      factor-beta1 (TGF-beta1) and then were treated with FD. Subsequently, NHLFs
      transfected with cav-1-siRNA were treated with TGF-beta1 and/or FD. The
      expressions of alpha-smooth muscle actin (alpha-SMA), fibronectin, collagen I,
      caveolin-1, phosphorylated extracellular signal-regulated kinase (p-ERK),
      phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated P38 were
      measured by Western blot and/or real-time polymerase chain reaction.
      Fluorofenidone attenuated TGF-beta1-induced expressions of alpha-SMA,
      fibronectin, and collagen I; inhibited phosphorylation of ERK, JNK, and P38; and
      restored caveolin-1 protein expression but cannot increase caveolin-1 mRNA level
      in vitro. After caveolin-1 was silenced, FD could not downregulate TGF-beta1
      induced expressions of alpha-SMA, fibronectin, and collagen I or phosphorylation
      of ERK, JNK, and P38. These studies demonstrate that FD, a potential antifibrotic
      agent, may attenuate TGF-beta1-induced activation of NHLFs by restoring the
      expression of caveolin-1. 

PMID- 25394238
TI  - Autophagy and checkpoints for intracellular pathogen defense.
AB  - PURPOSE OF REVIEW: Autophagy plays a crucial role in intracellular defense
      against various pathogens. Xenophagy is a form of selective autophagy that
      targets intracellular pathogens for degradation. In addition, several related,
      yet distinct, intracellular defense responses depend on autophagy-related genes.
      This review gives an overview of these processes, pathogen strategies to subvert
      them, and their crosstalk with various cell death programs. RECENT FINDINGS: The
      recruitment of autophagy-related proteins plays a key role in multiple
      intracellular defense programs, specifically xenophagy, microtubule-associated
      protein 1 light chain 3 alpha (LC3)-associated phagocytosis, and the interferon
      gamma-mediated elimination of pathogens, such as Toxoplasma gondii and murine
      norovirus. Recent progress has revealed methods employed by pathogens to resist
      these intracellular defense mechanisms and/or persist in spite of them. The
      intracellular pathogen load can tip the balance between cell survival and cell
      death. Further, it was recently observed that LC3-associated phagocytosis is
      indispensable for the efficient clearance of dying cells. SUMMARY: Autophagy
      dependent and autophagy-related gene-dependent pathways are essential in
      intracellular defense against a broad range of pathogens.

PMID- 25394240
TI  - Protection by enteral glutamine is mediated by intestinal epithelial cell
      peroxisome proliferator-activated receptor-gamma during intestinal
      ischemia/reperfusion.
AB  - We have demonstrated that enteral glutamine provides protection to the
      postischemic gut, and that peroxisome proliferator-activated receptor-gamma
      (PPARgamma) plays a role in this protection. Using Cre/lox technology to generate
      an intestinal epithelial cell (IEC)-specific PPARgamma null mouse model, we now
      investigated the contribution of IEC PPARgamma to glutamine's local and distant
      organ-protective effects. These mice exhibited absence of expression of PPARgamma
      in the intestine but normal PPARgamma expression in other tissues. After 1 h of
      intestinal ischemia under isoflurane anesthesia, wild-type and null mice received
      enteral glutamine (60 mM) or vehicle followed by 6 h of reperfusion or 7 days in
      survival experiments and compared with shams. Small intestine, liver, and lungs
      were analyzed for injury and inflammatory parameters. Glutamine provided
      significant protection against gut injury and inflammation, with similar
      protection in the lung and liver. Changes in systemic tumor necrosis factor-alpha
      reflected those seen in the injured organs. Importantly, mice lacking IEC
      PPARgamma had worsened injury and inflammation, and glutamine lost its protective
      effects in the gut and lung. The survival benefit found in glutamine-treated wild
      type mice was not observed in null mice. Using an IEC-targeted loss-of-function
      approach, these studies provide the first in vivo confirmation in native small
      intestine and lung that PPARgamma is responsible for the protective effects of
      enteral glutamine in reducing intestinal and lung injury and inflammation and
      improving survival. These data suggest that early enteral glutamine may be a
      potential therapeutic modality to reduce shock-induced gut dysfunction and
      subsequent distant organ injury. 

PMID- 25394241
TI  - Circulating iFABP Levels as a marker of intestinal damage in trauma patients.
AB  - Both the initial trauma and the subsequent hemodynamic instability may contribute
      to intestinal damage, which is of great importance in (immunological) posttrauma
      complications. This study assesses intestinal damage using the biomarker
      intestinal Fatty Acid Binding Protein (iFABP) in trauma patients during the first
      days of their hospital admission and the risk factors involved. Plasma iFABP
      levels were measured in blood samples obtained from adult multiple trauma
      patients (n = 93) at the trauma scene by the Helicopter Emergency Medical
      Services, at arrival at the emergency department (ED), and at days 1, 3, 5, 7,
      10, and 14 after trauma and related to injury severity and hemodynamic
      parameters. Plasma iFABP concentrations showed highest levels immediately after
      trauma at time points Helicopter Emergency Medical Services and ED. Nonsurvivors
      demonstrated higher iFABP levels at the ED compared with survivors. Furthermore,
      iFABP values at the ED correlated with Injury Severity Scores, and patients
      suffering from abdominal trauma demonstrated significantly higher iFABP
      concentrations in comparison with patients with other types of trauma or healthy
      controls. Also, patients presenting with a mean arterial pressure (MAP) less than
      70 mmHg at the ED demonstrated significantly higher plasma iFABP concentrations
      in comparison with patients with a normal (70-99 mmHg) or high (>100 mmHg) MAP or
      healthy controls. Finally, patients with a low hemoglobin (Hb) (<80% of reference
      value) displayed significantly higher iFABP concentrations in comparison with
      patients with a normal Hb or healthy controls. Plasma iFABP levels, indicative of
      intestinal injury, are increased immediately after trauma in patients with
      abdominal trauma, low MAP, or low Hb and are related to the severity of the
      trauma. As intestinal injury is suggested to be related to late complications,
      such as multiorgan dysfunction syndrome or sepsis in trauma patients, strategies
      to prevent intestinal damage after trauma could be of benefit to these patients. 

PMID- 25394242
TI  - Soluble RAGE and the RAGE ligands HMGB1 and S100A12 in critical illness: impact
      of glycemic control with insulin and relation with clinical outcome.
AB  - Systemic inflammation often leads to complications in critically ill patients.
      Activation of the receptor for advanced glycation end-products (RAGE) generates
      inflammatory cytokines, proteases, and oxidative stress and may link inflammation
      to subsequent organ damage. Furthermore, hyperglycemia-induced oxidative stress
      increases RAGE ligands and RAGE expression. We hypothesized that preventing
      hyperglycemia during critical illness reduces the risk of excessively enhanced
      RAGE signaling, which could relate to clinical outcomes and risk of death. In 405
      long-stay surgical intensive care unit patients randomized to intensive or
      conventional insulin treatment, serum concentrations of soluble RAGE (decoy
      receptor) and the RAGE ligands high-mobility group box 1 (HMGB1) and S100A12 were
      measured on admission, day 7, and last day. These were compared with levels in 71
      matched control subjects and with C-reactive protein (CRP) as a routinely
      monitored inflammation marker. On admission, soluble RAGE, HMGB1, S100A12, and
      CRP were higher in patients than in controls. The HMGB1, S100A12, and CRP
      remained elevated throughout intensive care unit stay, whereas soluble RAGE
      decreased to levels lower than in controls by day 7. Unexpectedly, insulin
      treatment did not affect the circulating levels of these markers. In univariable
      analysis, elevated levels of soluble RAGE on admission were associated with
      adverse outcome, including circulatory failure, kidney failure, liver
      dysfunction, and mortality. The associations with circulatory and kidney failure
      remained significant in multivariable logistic regression analysis corrected for
      baseline risk factors. Critical illness affects components of RAGE signaling,
      unaffected by insulin treatment. Elevated on-admission soluble RAGE was
      associated with adverse outcomes. 

PMID- 25394243
TI  - Comparison of Decision-Assist and Clinical Judgment of Experts for Prediction of
      Lifesaving Interventions.
AB  - Early recognition of hemorrhage during the initial resuscitation of injured
      patients is associated with improved survival in both civilian and military
      casualties. We tested a transfusion and lifesaving intervention (LSI) prediction
      algorithm in comparison with clinical judgment of expert trauma care providers.
      We collected 15 min of pulse oximeter photopletysmograph waveforms and extracted
      features to predict LSIs. We compared this with clinical judgment of LSIs by
      individual categories of prehospital providers, nurses, and physicians and a
      combined judgment of all three providers using the Area Under Receiver Operating
      Curve (AUROC). We obtained clinical judgment of need for LSI from 405 expert
      clinicians in135 trauma patients. The pulse oximeter algorithm predicted
      transfusion within 6 h (AUROC, 0.92; P < 0.003) more accurately than either
      physicians or prehospital providers and as accurately as nurses (AUROC, 0.76; P =
      0.07). For prediction of surgical procedures, the algorithm was as accurate as
      the three categories of clinicians. For prediction of fluid bolus, the diagnostic
      algorithm (AUROC, 0.9) was significantly more accurate than prehospital providers
      (AUROC, 0.62; P = 0.02) and nurses (AUROC, 0.57; P = 0.04) and as accurate as
      physicians (AUROC, 0.71; P = 0.06). Prediction of intubation by the algorithm
      (AUROC, 0.92) was as accurate as each of the three categories of clinicians. The
      algorithm was more accurate (P < 0.03) for blood and fluid prediction than the
      combined clinical judgment of all three providers but no different from the
      clinicians in the prediction of surgery (P = 0.7) or intubation (P = 0.8).
      Automated analysis of 15 min of pulse oximeter waveforms predicts the need for
      LSIs during initial trauma resuscitation as accurately as judgment of expert
      trauma clinicians. For prediction of emergency transfusion and fluid bolus, pulse
      oximetry features were more accurate than these experts. Such automated decision
      support could assist resuscitation decisions, trauma team, and operating room and
      blood bank preparations. 

PMID- 25394244
TI  - Inhibition of glycogen synthase kinase-3beta attenuates organ injury and
      dysfunction associated with liver ischemia-reperfusion and thermal injury in the
      rat.
AB  - Glycogen synthase kinase 3 (GSK-3) is a serine-threonine kinase discovered
      decades ago to have an important role in glycogen metabolism. Today, we know that
      this kinase is involved in the regulation of many cell functions, including
      insulin signaling, specification of cell fate during embryonic development, and
      the control of cell division and apoptosis. Insulin and TDZD-8 (4-benzyl-2-methyl
      1,2,4-thiadiazolidine-3,5-dione) are inhibitors of GSK-3beta that have been shown
      to possess organ-protective effects in inflammatory-mediated organ injury models.
      We aimed to evaluate the cytoprotective effect of GSK-3beta inhibition on rat
      models of liver ischemia-reperfusion and thermal injury. In the liver ischemia
      reperfusion model, TDZD-8 and insulin were administered at 5 mg/kg (i.v.) and 1.4
      IU/kg (i.v.), respectively, 30 min before induction of ischemia and led to the
      significant reduction of the serum concentration of aspartate aminotransferase,
      alanine aminotransferase, gamma-glutamyltransferase, and lactate dehydrogenase.
      Beneficial effects were found to be independent from blood glucose levels. In the
      thermal injury model, TDZD-8 was administered at 5 mg/kg (i.v.) 5 min before
      induction of injury and significantly reduced multiple organ dysfunction markers
      (liver, neuromuscular, and lung). In the lung, TDZD-8 reduced the histological
      signs of tissue injury, inflammatory markers (cytokines), and neutrophil
      chemotaxis/infiltration; reduced GSK-3beta, nuclear factor-kappaB, and Akt
      activation; reduced caspase-3 and metalloproteinase-9 activation. Our study
      provides a new insight on the beneficial effects of GSK-3beta inhibition on
      systemic inflammation and further elucidates the mechanism and pathway crosstalks
      by which TDZD-8 reduces the multiple organ injury elicited by thermal injury. 

PMID- 25394245
TI  - Expression profile of MicroRNAs in gram-negative bacterial sepsis.
AB  - Bacterial lipopolysaccharide (LPS) is an effective trigger of the inflammatory
      response during infection with gram-negative bacilli (GNB), which implicates the
      pathogenesis of sepsis and septic shock. MicroRNAs (miRNAs) are shown to have a
      significant role in the fine-tuning of toll-like receptor (TLR)-mediated
      inflammatory response. We profiled miRNA expression levels in peripheral
      leukocytes of GNB urosepsis patients and compared them with those of healthy
      controls. We further explored the regulatory mechanism of endotoxin-responsive
      miRNAs in TLR and cytokine signaling by using human monocytic cell line (THP-1
      cells) treated with LPS antigen stimulation. The expression of two miRNAs, that
      is, let-7a (P < 0.001) and miR-150 (P < 0.001), were confirmed to be
      significantly downregulated in GNB urosepsis patients compared with healthy
      controls. The expression of let-7a is first to be identified as a biomarker of
      GNB sepsis. By using an in vitro model with the human monocytic cell line, we
      demonstrated that LPS stimulation downregulated the THP-1 cell expression of let
      7a. The downregulation of let-7a is correlated with the induced expression of
      cytokine-inducible Src homology 2-containing protein without change in cytokine
      inducible Src homology 2-containing protein mRNA levels in THP-1 cells via TLR
      signaling pathway activation. Moreover, gain of function by overexpression of let
      7a revealed that let-7a significantly decreased tumor necrosis factor-alpha and
      interleukin-1beta production in response to LPS. Reduced let-7a and miR-150
      levels in peripheral leukocytes correlate with GNB urosepsis patients.
      Furthermore, let-7a is relevant to the regulation of TLR-mediated innate immune
      response. 

PMID- 25394246
TI  - Prediction of ATLS hypovolemic shock class in rats using the perfusion index and
      lactate concentration.
AB  - It is necessary to quickly and accurately determine Advanced Trauma Life Support
      (ATLS) hemorrhagic shock class for triage in cases of acute hemorrhage caused by
      trauma. However, the ATLS classification has limitations, namely, with regard to
      primary vital signs. This study identified the optimal variables for appropriate
      triage of hemorrhage severity, including the peripheral perfusion index and serum
      lactate concentration in addition to the conventional primary vital signs. To
      predict the four ATLS classes, three popular machine learning algorithms with
      four feature selection methods for multicategory classification were applied to a
      rat model of acute hemorrhage. A total of 78 anesthetized rats were divided into
      four groups for ATLS classification based on blood loss (in percent). The support
      vector machine one-versus-one model with the Kruskal-Wallis feature selection
      method performed best, with 80.8% accuracy, relative classifier information of
      0.629, and a kappa index of 0.732. The new hemorrhage-induced severity index
      (lactate concentration/perfusion index), diastolic blood pressure, mean arterial
      pressure, and the perfusion index were selected as the optimal variables for
      predicting the four ATLS classes by support vector machine one-versus-one with
      the Kruskal-Wallis method. These four variables were also selected for binary
      classification to predict ATLS classes I and II versus III and IV for blood
      transfusion requirement. The suggested ATLS classification system would be
      helpful to first responders by indicating the severity of patients, allowing
      physicians to prepare suitable resuscitation before hospital arrival, which could
      hasten treatment initiation. 

PMID- 25394247
TI  - Cardiopulmonary Arrest and Resuscitation in Severe Sepsis and Septic Shock: A
      Research Model.
AB  - Cardiopulmonary resuscitation in patients with severe sepsis and septic shock is
      challenging and usually unsuccessful. The aim of the present study is to describe
      our swine model of cardiac arrest and resuscitation in severe sepsis and septic
      shock. In this prospective randomized animal study, 10 healthy female Landrace
      Large White pigs with an average weight of 20 +/- 1 kg (aged 19 - 21 weeks) were
      the study subjects. Septicemia was induced by an intravenous infusion of a bolus
      of 20-mL bacterial suspension in 2 min, followed by a continuous infusion during
      the rest of the experiment. After septic shock was confirmed, the animals were
      left untreated until cardiac arrest occurred. All animals developed pulseless
      electrical activity between the fifth and sixth hours of septicemia, whereas five
      (50%) of 10 animals were successfully resuscitated. Coronary perfusion pressure
      was statistically significantly different between surviving and nonsurviving
      animals. We found a statistically significant correlation between mean arterial
      pressure and unsuccessful resuscitation (P = 0.046), whereas there was no
      difference in end-tidal carbon dioxide (23.05 +/- 1.73 vs. 23.56 +/- 1.70; P =
      0.735) between animals with return of spontaneous circulation and nonsurviving
      animals. During the 45-min postresuscitation monitoring, we noted a significant
      decrease in hemodynamic parameters, although oxygenation indices and lactate
      clearance were constantly increased (P = 0.001). This successful basic swine
      model was for the first time developed and may prove extremely useful in future
      studies on the periarrest period in severe sepsis and septic shock. 

PMID- 25394248
TI  - Long-term outcomes after severe shock.
AB  - Severe shock is a life-threatening condition with very high short-term mortality.
      Whether the long-term outcomes among survivors of severe shock are similar to
      long-term outcomes of other critical illness survivors is unknown. We therefore
      sought to assess long-term survival and functional outcomes among 90-day
      survivors of severe shock and determine whether clinical predictors were
      associated with outcomes. Seventy-six patients who were alive 90 days after
      severe shock (received >=1 MUg/kg per minute of norepinephrine equivalent) were
      eligible for the study. We measured 3-year survival and long-term functional
      outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the
      EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event
      Scale-Revised, and an employment instrument. We also assessed the relationship
      between in-hospital predictors and long-term outcomes. The mean long-term
      survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were
      eligible for follow-up. Patients who died were older than patients who survived.
      Thirty-six patients completed a telephone interview a mean of 5 years after
      hospital admission. The patients' Physical Functioning scores were below U.S.
      population norms (P < 0.001), whereas mental health scores were similar to
      population norms. Nineteen percent of the patients had symptoms of depression,
      39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress
      disorder. Thirty-six percent were disabled, and 17% were working full-time. Early
      survivors of severe shock had a high 3-year survival rate. Patients' long-term
      physical and psychological outcomes were similar to those reported for cohorts of
      less severely ill intensive care unit survivors. Anxiety and depression were
      relatively common, but only a few patients had symptoms of posttraumatic stress
      disorder. This study supports the observation that acute illness severity does
      not determine long-term outcomes. Even extremely critically ill patients have
      similar outcomes to general intensive care unit survivor populations.

PMID- 25394249
TI  - Hyperactive Human Glucocorticoid Receptor Isoforms and their Implications for the
      Stress Response.
AB  - Glucocorticoids are indispensable therapeutic agents in diseases of inflammation,
      but their effectiveness in treating advanced septic shock has been inconsistent.
      Our understanding of the mechanisms causing this variability to steroid therapy
      remains limited. Previous studies in our laboratory have implicated human
      glucocorticoid receptor (hGR) polymorphisms as one of the likely reasons for this
      variability. We examined the effect of two single-nucleotide polymorphisms (SNPs)
      on the transactivation potential of the hGR in the absence and presence of
      exogenous steroids. An isoform containing a novel naturally occurring human SNP,
      T1463C, was found to have a hyperactive response with treatment of all three
      steroids examined while maintaining low activity in the absence of steroids,
      relative to reference hGR. In comparison, another hGR isoform with the A2297G
      SNP, previously identified in our laboratory, demonstrated hyperactive
      transactivational response in the absence of steroids; however, it had a
      significant increase in activity after treatment with only one of the
      glucocorticoids (hydrocortisone) tested. These results offer a possible
      explanation for the clinical variability seen among individuals in response to
      stress or shock. 

PMID- 25394250
TI  - Role of Serotonin in MODS: Deficiency of Serotonin Protects Against Zymosan
      Induced Multiple Organ Failure in Mice.
AB  - Zymosan-induced multiple organ dysfunction syndrome (MODS) is a multifactorial
      pathology that involves the deterioration of function of several organs. 5
      Hydroxytryptamine (5-HT) is a small monoamine molecule that is primarily known
      for its role as a neurotransmitter. Previous studies have shown that 5-HT could
      serve as an important inflammatory mediator in the peripheral immune system. In
      the present study, we investigated the effect of 5-HT on the development of non
      septic shock caused by zymosan in mice. Tryptophan hydroxylase 1-knockout mice
      (TPH1, leading to the absence of 5-HT), TPH1 + 5-hydroxytryptophan (precursor of
      5-HT) treatment mice, wild-type (TPH1) mice, and wild-type plus p
      chlorophenylalanine (PCPA, TPH1 inhibitor) treatment mice received zymosan
      intraperitoneally at a dose of 500 mg/kg. Organ failure and systemic inflammation
      in the mice were assessed 18 h after the administration of zymosan. Deficiency of
      5-HT caused a significant reduction of the 1) peritoneal exudate formation, 2)
      neutrophil infiltration, 3) MODS, 4) nitrosative stress, and 5) cytokine
      formation. In addition, at the end of the observation period (7 days), deficiency
      of 5-HT in the mice was shown to be able to alleviate the severe illness
      characterized as systemic toxicity, significant loss of body weight, and high
      mortality caused by zymosan. In conclusion, the lack of 5-HT by genetic knockout
      or by pharmacologic inhibition of the TPH1 enzyme significantly attenuated
      zymosan-induced MODS. 

PMID- 25394251
TI  - Cytidine 5'-diphosphocholine differentially affects hemostatic parameters in
      diverse conditions in rats: an investigation via thromboelastography.
AB  - Cytidine 5'-diphosphocholine (CDP-choline) has several physiological and
      pharmacological effects on various bodily functions, including hemostasis. This
      study determined the impact of CDP-choline on hemostasis in a trauma-hemorrhage
      (T-H) model in rats or under in vitro conditions or after chronic treatment via
      thromboelastography. Trauma-hemorrhage resuscitation was induced, and either
      saline (1 mL/kg) or CDP-choline (50 mg/kg) was injected intravenously just prior
      to resuscitation in the T-H group and at the same time point in the sham-control
      group. The effects of CDP-choline on thromboelastogram parameters, coagulation
      markers, and platelet aggregation were investigated under in vitro conditions
      (1.5 mM, 30- or 3-min incubation in blood or plasma) and after chronic use (50
      mg/kg, i.p., 10 days). Acute CDP-choline treatment was shown to decrease the
      initial and maximum clot formation time, accelerate clotting rapidity, reduce the
      lysis percentage, and increase the coagulation index in the T-H resuscitation
      group, whereas the same treatment in the sham-control rats did not alter any of
      the thromboelastogram parameters. However, the incubation of whole blood with CDP
      choline prolonged the initial and maximum clot formation time, and CDP-choline
      treatment significantly decreased the slopes of the disaggregation and
      aggregation curves when platelets were stimulated with ADP and collagen,
      respectively. Interestingly, the chronic use of this drug did not influence any
      of these hemostatic parameters. These data implicate that acute but not chronic
      CDP-choline administration may differentially alter the hemostatic parameters
      under diverse conditions. The drug may produce a hypercoagulable state in
      activated situations but cause opposite effects under normal in vitro conditions.

PMID- 25394252
TI  - Integrin antagonist augments the therapeutic effect of adenovirus-mediated
      REIC/Dkk-3 gene therapy for malignant glioma.
AB  - Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) was identified
      as a gene whose expression is reduced in many human cancers. REIC/Dkk-3
      expression is also downregulated in malignant glioma and regulates cell growth
      through caspase-dependent apoptosis. cRGD (EMD121974), an antagonist of
      integrins, has demonstrated preclinical efficacy against malignant glioma. In
      this study, we investigated the antiglioma effect of combination therapy using an
      adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) and cRGD. Quantitative real-time
      reverse-transcription PCR revealed the reduction of REIC/Dkk-3 mRNA levels in
      malignant glioma cell lines. The reduction of REIC/Dkk-3 protein expression in
      malignant glioma cell lines was also confirmed with western blot analysis. After
      treatment with Ad-REIC and cRGD, the proliferative rate of malignant glioma cells
      was significantly reduced in a time-dependent manner. In vivo, there was a
      statistically significant increase in the survival of mice treated with Ad-REIC
      and cRGD combination therapy compared with Ad-REIC monotherapy. We identified an
      apoptotic effect following monotherapy with Ad-REIC. Moreover, cRGD augmented the
      antiglioma efficacy of Ad-REIC. These results may lead to a promising new
      approach for the treatment of malignant glioma. 

PMID- 25394253
TI  - Prevention of hepatitis C virus infection by adoptive allogeneic immunotherapy
      using suicide gene-modified lymphocytes: an in vitro proof-of-concept.
AB  - Hepatitis C virus (HCV)-induced, end-stage liver disease is a major indication
      for liver transplantation, but systematic graft reinfection accelerates liver
      disease recurrence. Transplantation recipients may be ineligible for direct
      acting antivirals, owing to toxicity, resistance or advanced liver disease.
      Adoptive immunotherapy with liver graft-derived, ex vivo-activated lymphocytes
      was previously shown to prevent HCV-induced graft reinfections. Alternatively,
      the applicability and therapeutic efficacy of adoptive immunotherapy may be
      enhanced by 'ready for use' suicide gene-modified lymphocytes from healthy blood
      donors; moreover, conditional, prodrug-induced cell suicide may prevent potential
      side effects. Here, we demonstrate that allogeneic suicide gene-modified
      lymphocytes (SGMLs) could potently, dose- and time-dependently, inhibit viral
      replication. The effect occurs at effector:target cell ratios that exhibits no
      concomitant cytotoxicity toward virus-infected target cells. The effect, mediated
      mostly by CD56+ lymphocytes, is interleukin-2-dependent, IFN-gamma-mediated and,
      importantly, resistant to calcineurin inhibitors. Thus, post-transplant
      immunosuppression may not interfere with this adoptive cell immunotherapy
      approach. Furthermore, these cells are indeed amenable to conditional cell
      suicide; in particular, the inducible caspase 9 suicide gene is superior to the
      herpes simplex virus thymidine kinase suicide gene. Our data provide in vitro
      proof-of-concept that allogeneic, third-party, SGMLs may prevent HCV-induced
      liver graft reinfection.

PMID- 25394254
TI  - Acute flaccid paralysis following enterovirus D68 associated pneumonia, France,
      2014.
AB  - Human enterovirus D68 (EV-D68) is known to be associated with mild to severe
      respiratory infections. Recent reports in the United States and Canada of acute
      flaccid paralysis (AFP) in children with detection of EV-D68 in respiratory
      samples have raised concerns about the aetiological role of this EV type in
      severe neurological disease. This case study is the first report of AFP following
      EV-D68 infection in Europe.

PMID- 25394255
TI  - High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in
      France, March 2014.
AB  - We report the first case in France of a high-level azithromycin-resistant
      Neisseria gonorrhoeae (minimum inhibitory concentration (MIC) = 96 mg/L) assigned
      to MLST7363 (NG-MAST ST6360), also resistant to ciprofloxacin and tetracycline
      but susceptible to ceftriaxone. The patient was a 51 year-old heterosexual man
      who returned following 1g azithromycin monotherapy. Mechanisms of azithromycin
      resistance were a C2599T mutation in the four copies of the rrl gene and a novel
      mutation in the promoter of the mtrR gene.

PMID- 25394256
TI  - Did introduction of pneumococcal vaccines in the Netherlands decrease the need
      for respiratory antibiotics in children? Analysis of 2002 to 2013 data.
AB  - To estimate the effect of the introduction of the 7- and 10-valentpneumococcal
      vaccines in 2006 and 2011, respectively in the Netherlands, we assessed
      respiratory antibiotic use in one to nine year-old children between 2002 and
      2013. Seasonal autoregressive integrated moving-average models were applied to
      estimate the percentage reduction in respiratory antibiotic use. When compared
      with the pre-vaccination period, the proportion of respiratory antibiotic
      prescriptions fell by 4.94% (95% CI: 4.63 to 5.26) and 9.02% (95% CI: 2.83 to
      14.82) after the introduction of the 7-valent vaccine in children aged three and
      four years, respectively. After the introduction of the 10-valent vaccine, we
      observed a reduction of 13.04% (95% CI: 2.76 to 22.23), 20.31% (95% CI: 13.50 to
      26.58), 16.92% (95% CI: 3.07 to 28.80), 22.34% (95% CI: 3.73 to 37.35), 23.75%
      (95% CI: 2.37 to 40.44) in two, three, four, six and seven year-old children,
      respectively. Thus, our results indicate a reduction in respiratory antibiotic
      prescriptions in young children after introduction of the pneumococcal vaccines.
      As only children in our study population aged one and two years born after March
      2011 had received the 10-valent vaccine, the effects of the 10-valent vaccine in
      children aged three to nine years likely reflect the effects of the 7-valent
      vaccine and herd immunity.

PMID- 25394257
TI  - The experience of West Nile virus integrated surveillance system in the Emilia
      Romagna region: five years of implementation, Italy, 2009 to 2013.
AB  - Predicting West Nile virus (WNV) circulation and the risk of WNV epidemics is
      difficult due to complex interactions of multiple factors involved. Surveillance
      systems that timely detect virus activity in targeted areas, and allow evidence
      based risk assessments may therefore be necessary. Since 2009, a system
      integrating environmental (mosquitoes and birds) and human surveillance has been
      implemented and progressively improved in the Emilia-Romagna region, Italy. The
      objective is to increase knowledge of WNV circulation and to reduce the
      probability of virus transmission via blood, tissue and organ donation. As of
      2013, the system has shown highly satisfactory results in terms of early
      detection capacity (the environmental surveillance component allowed detection of
      WNV circulation 3-4 weeks before human cases of West Nile neuroinvasive disease
      (WNND) occurred), sensitivity (capacity to detect virus circulation even at the
      enzootic level) and area specificity (capacity to indicate the spatial
      distribution of the risk for WNND). Strong correlations were observed between the
      vector index values and the number of human WNND cases registered at the province
      level. Taking into consideration two scenarios of surveillance, the first with
      environmental surveillance and the second without, the total costs for the period
      from 2009 to 2013 were reduced when environmental surveillance was considered
      (EUR 2.093 million for the first scenario vs EUR 2.560 million for the second).
      Environmental surveillance helped to reduce costs by enabling a more targeted
      blood unit testing strategy. The inclusion of environmental surveillance also
      increased the efficiency of detecting infected blood units and further allowed
      evidence-based adoption of preventative public health measures.

PMID- 25394258
TI  - Four-month outbreak of invasive meningococcal disease caused by a rare serogroup
      B strain, identified through the use of molecular PorA subtyping, England, 2013.
AB  - Molecular PorA subtyping provides information that increasingly requires the
      adaptation of standard public health approaches to outbreak management. We report
      an outbreak of a rare subtype of meningococcal infection not previously
      identified in the United Kingdom (UK). The outbreak occurred in the Warwickshire
      area in England between February and June 2013. Molecular subtyping allowed the
      identification of additional cases, prompting an enhanced public health response
      that included efforts to identify potential social networks that might benefit
      from chemoprophylaxis. It also prompted swabbing to define nasopharyngeal
      carriage in the focal nursery and helped explain the unusual epidemiological
      pattern. Without subtyping to identify a link, the additional cases would have
      been managed as sporadic cases in accordance with current UK guidance.

PMID- 25394261
TI  - A decision theoretic approach to optimization of multiple testing procedures.
AB  - This paper focuses on the concept of optimizing a multiple testing procedure
      (MTP) with respect to a predefined utility function. The class of Bonferroni
      based closed testing procedures, which includes, for example, (weighted) Holm,
      fallback, gatekeeping, and recycling/graphical procedures, is used in this
      context. Numerical algorithms for calculating expected utility for some MTPs in
      this class are given. The obtained optimal procedures, as well as the gain
      resulting from performing an optimization are then examined in a few, but
      informative, examples. 

PMID- 25394263
TI  - Arterio-venous malformations of uterus - diagnostic and management dilemmas.
AB  - Keeping in mind the life-threatening consequences of curettage in cases of
      undiagnosed uterine arterio-venous malformation (AVM), its possibility should be
      considered in patients presenting with abnormal heavy uterine bleeding and
      negative Human Chorionic Gonadotropin (beta-hCG) values. We collected a series of
      cases in which the patients presented with abnormal heavy uterine bleeding, some
      not responding to conservative treatment. In the presence of declining or low
      serum beta-hCG levels and ultrasound Doppler showing increased vascularity,
      patients were investigated to detect the possible presence of uterine AVM. In
      those patients in whom angiographic confirmation of uterine AVM was made,
      embolisation was done and the outcome was followed. In those patients in whom
      hysterectomy was done the histopathogy specimen was studied for the possible
      cause of increased vascularity. Arterio-venous shunting seen on ultrasound does
      not always imply a uterine AVM and some cases can present diagnostic and
      management dilemmas. 

PMID- 25394262
TI  - Modifications of human growth differentiation factor 9 to improve the generation
      of embryos from low competence oocytes.
AB  - Growth differentiation factor 9 (GDF9) is an oocyte-derived growth factor that
      plays a critical role in ovarian folliculogenesis and oocyte developmental
      competence and belongs to the TGF-beta family of proteins. Recombinant human GDF9
      (hGDF9) is secreted in a latent form, which in the case of the fully processed
      protein, has the proregion noncovalently associated with the mature region. In
      this study, we investigated a number of amino acid residues in the mature region
      of hGDF9 that are different from the corresponding residues in the mouse protein,
      which is not latent. We designed, expressed, and purified 4 forms of chimeric
      hGDF9 (M1-M4) that we found to be active in a granulosa cell bioassay. Using a
      porcine in vitro maturation model with inherent low developmental competence
      (yielding 10%-20% blastocysts), we tested the ability of the chimeric hGDF9
      proteins to improve oocyte maturation and developmental competence.
      Interestingly, one of the chimeric proteins, M3, was able to significantly
      increase the level of embryo production using such low competence oocytes. Our
      molecular modeling studies suggest that in the case of hGDF9 the Gly(391)Arg
      mutation probably increases receptor binding affinity, thereby creating an active
      protein for granulosa cells in vitro. However, for an improvement in oocyte
      developmental competence, a second mutation (Ser(412)Pro), which potentially
      decreases the affinity of the mature region for the proregion, is also required. 

PMID- 25394264
TI  - Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin
      and hesperetin: an updated review of their molecular mechanisms and experimental
      models.
AB  - Inflammation and oxidative stress are two major causes of various life
      threatening diseases. Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are
      two flavonoids from citrus species that have numerous biological properties,
      particularly antioxidant and anti-inflammatory. New findings showed that the
      antioxidant activity of Hsd/Hst was not only limited to its radical scavenging
      activity, but it augmented the antioxidant cellular defenses via the ERK/Nrf2
      signaling pathway as well. Various in vitro and in vivo studies have been
      conducted to evaluate Hsd, its metabolites, or its synthetic derivatives at
      reducing inflammatory targets including NF-kappaB, iNOS, and COX-2, and the
      markers of chronic inflammation. In this review, new findings regarding the
      molecular targets of Hsd and Hst in the reduction of oxidative stress are
      discussed. Also, in the anti-inflammatory section, we provide a summary of
      significant investigations concerning the mechanisms of action based on the
      studied inflammation models.

PMID- 25394265
TI  - Unambiguous assignment of short- and long-range structural restraints by solid
      state NMR spectroscopy with segmental isotope labeling.
AB  - We present an efficient method for the reduction of spectral complexity in the
      solid-state NMR spectra of insoluble protein assemblies, without loss of signal
      intensity. The approach is based on segmental isotope labeling by using the split
      intein DnaE from Nostoc punctiforme. We show that the segmentally (13)C, (15)N
      labeled prion domain of HET-s exhibits significantly reduced spectral overlap
      while retaining the wild-type structure and spectral quality. A large number of
      unambiguous distance restraints were thus collected from a single two-dimensional
      (13)C, (13)C cross-correlation spectrum. The observed resonances could be
      unambiguously identified as intramolecular without the need for preparing a
      dilute, less sensitive sample.

PMID- 25394266
TI  - Programmed photodegradation of polymeric/oligomeric materials derived from
      renewable bioresources.
AB  - Renewable polymeric materials derived from biomass with built-in phototriggers
      were synthesized and evaluated for degradation under irradiation of UV light.
      Complete decomposition of the polymeric materials was observed with recovery of
      the monomer that was used to resynthesize the polymers. 

PMID- 25394268
TI  - Parallel-plate waveguide for volume radio frequency transmission in MRI.
AB  - PURPOSE: Radiofrequency coils in MRI are narrowband resonant structures. The high
      quality factor makes their performance sensitive to loading and other operating
      conditions. We developed a new coil to provide volume transmit in a broad
      frequency band. METHODS: The proposed coil is a parallel-plate waveguide. When
      operating in the transverse electromagnetic mode, a uniform magnetic field is
      generated between the plates for imaging. The impedance of the transverse
      electromagnetic mode is matched by a broadband matching circuit. The two plates
      are actively driven with broadband Wilkinson power dividers and combiners. Re
      entrant design is further applied to improve the overall efficiency. RESULTS: We
      developed a prototype of a coil to image the human forearm with a bandwidth of
      more than one octave. Its feasibility was demonstrated by proton imaging and
      phosphorous spectroscopy at 7T. CONCLUSIONS: The proposed coil structure is
      compact and relatively easier to construct. It can be applied for volume
      radiofrequency transmit in MRI in a broad frequency band.

PMID- 25394269
TI  - Hox and ParaHox genes: a review on molluscs.
AB  - Hox and ParaHox genes are involved in patterning the anterior-posterior body axis
      in metazoans during embryo development. Body plan evolution and diversification
      are affected by variations in the number and sequence of Hox and ParaHox genes,
      as well as by their expression patterns. For this reason Hox and ParaHox gene
      investigation in the phylum Mollusca is of great interest, as this is one of the
      most important taxa of protostomes, characterized by a high morphological
      diversity. The comparison of the works reviewed here indicates that species of
      molluscs, belonging to different classes, share a similar composition of Hox and
      ParaHox genes. Therefore evidence suggests that the wide morphological diversity
      of this taxon could be ascribed to differences in Hox gene interactions and
      expressions and changes in the Hox downstream genes rather than to Hox cluster
      composition. Moreover the data available on Hox and ParaHox genes in molluscs
      compared with those of other Lophotrochozoa shed light on the complex and
      controversial evolutionary histories that these genes have undergone within
      protostomes.

PMID- 25394267
TI  - Multiple dimensions of epigenetic gene regulation in the malaria parasite
      Plasmodium falciparum: gene regulation via histone modifications, nucleosome
      positioning and nuclear architecture in P. falciparum.
AB  - Plasmodium falciparum is the most deadly human malarial parasite, responsible for
      an estimated 207 million cases of disease and 627,000 deaths in 2012. Recent
      studies reveal that the parasite actively regulates a large fraction of its genes
      throughout its replicative cycle inside human red blood cells and that
      epigenetics plays an important role in this precise gene regulation. Here, we
      discuss recent advances in our understanding of three aspects of epigenetic
      regulation in P. falciparum: changes in histone modifications, nucleosome
      occupancy and the three-dimensional genome structure. We compare these three
      aspects of the P. falciparum epigenome to those of other eukaryotes, and show
      that large-scale compartmentalization is particularly important in determining
      histone decomposition and gene regulation in P. falciparum. We conclude by
      presenting a gene regulation model for P. falciparum that combines the described
      epigenetic factors, and by discussing the implications of this model for the
      future of malaria research. 

PMID- 25394270
TI  - Virtual reality improves sleep quality amongst older adults with disabilities.

PMID- 25394271
TI  - Determining a cutoff score of caregiver burden for predicting depression among
      family caregivers in a large population-based sample.

PMID- 25394272
TI  - Staff confidence, morale and attitudes in a specialist unit for general hospital
      patients with dementia and delirium--a qualitative study.

PMID- 25394273
TI  - Ultrasonography and electrodiagnostic studies in ulnar neuropathy: an examination
      of the sensitivity and specificity and the correlations between both diagnostic
      tools.
AB  - PURPOSE: This study determines the sensitivity and specificity of ultrasonography
      (US) and electrodiagnostic studies in ulnar neuropathy at the elbow (UNE) in
      clinical practice and explores the correlation between both diagnostic tools.
      METHODS: Patients were classified on clinical grounds as UNE or patient controls.
      Electrodiagnostic studies were performed, and nerve cross-sectional area was
      measured by US. RESULTS: Sensitivity and specificity were examined in 30 cases of
      UNE and 33 patient controls. Electrodiagnostic studies had a sensitivity for UNE
      of 63.3% and a specificity of 87.9%. Ultrasonography had a sensitivity of 76.7%
      and a specificity of 72.7%. Ultrasonography is more sensitive if complaints exist
      for 6 months or less. If complaints persisted for more than 6 months, sensitivity
      and specificity of the electrodiagnostic studies were superior. Correlation was
      examined in 30 cases of UNE. There was no significant correlation between cross
      sectional area and absolute motor nerve conduction velocities across the elbow,
      motor nerve conduction velocities slowing across the elbow, and compound muscle
      action potentials amplitude reduction. CONCLUSIONS: Ultrasonography is more
      sensitive if complaints exist for 6 months or less. Electrodiagnostic studies are
      more sensitive and specific compared with US for longer existing cases of UNE. No
      significant correlation could be demonstrated between both diagnostic tools.

PMID- 25394274
TI  - Hybrid MPI/OpenMP parallelization of the effective fragment potential method in
      the libefp software library.
AB  - A new hybrid MPI/OpenMP parallelization scheme is introduced for the Effective
      Fragment Potential (EFP) method implemented in the libefp software library. The
      new implementation employs dynamic load balancing algorithm that uses a
      master/slave model. The software shows excellent parallel scaling up to several
      hundreds of CPU-cores across multiple nodes. The code uses functions only from
      the well-established MPI-1 standard that simplifies portability of the library.
      This new parallel EFP implementation greatly expands the applicability of the EFP
      and QM/EFP methods by extending attainable time- and length-scales.

PMID- 25394275
TI  - Diversity of small RNAs expressed in Pseudomonas species.
AB  - RNA sequencing (RNA-seq) has revealed several hundreds of previously undetected
      small RNAs (sRNAs) in all bacterial species investigated, including strains of
      Pseudomonas aeruginosa, Pseudomonas putida and Pseudomonas syringae. Nonetheless,
      only little is known about the extent of conservation of expressed sRNAs across
      strains and species. In this study, we have used RNA-seq to identify sRNAs in P.
      putida DOT-T1E and Pseudomonas extremaustralis 14-3b. This is the first strain of
      P. extremaustralis and the second strain of P. putida to have their
      transcriptomes analysed for sRNAs, and we identify the presence of around 150
      novel sRNAs in each strain. Furthermore, we provide a comparison based on
      sequence conservation of all the sRNAs detected by RNA-seq in the Pseudomonas
      species investigated so far. Our results show that the extent of sRNA
      conservation across different species is very limited. In addition, when
      comparing the sRNAs expressed in different strains of the same species, we
      observe that numerous sRNAs exhibit a strain-specific expression pattern. These
      results support the idea that the evolution of most bacterial sRNAs is rapid,
      which limits the extent of both interspecies and intraspecies conservation.

PMID- 25394276
TI  - Influence of animal husbandry practices on void spot assay outcomes in C57BL/6J
      male mice.
AB  - AIMS: Mice are increasingly being used as models to investigate aspects of
      urinary dysfunction that humans with lower urinary tract symptoms (LUTS)
      experience. One method used to examine voiding function is the spontaneous void
      spot assay. The purpose of this study was to characterize and identify animal
      husbandry conditions that might confound results of the spontaneous void spot
      assay in male C57Bl/6J mice. METHODS: Mice were placed in cages lined with filter
      paper for 4 hr and urine was visualized with UV transillumination. Voiding
      parameters including urine spot number, spot size, total urine area, primary void
      area, corner and center voiding were quantified. RESULTS: Adult male mice void
      more frequently with advancing age and a subpopulation (5-10%) display a frequent
      spotting pattern at 6-9 weeks of age. Voiding was not significantly different in
      male mice weaned to group housing (4-6 per cage) versus single housing, and was
      not altered when they were used as breeders. Voiding was changed upon
      transferring group housed adult males to single density cages, which decreased
      total urine area. Repeated assays of male voiding behavior over three consecutive
      days increased primary void area by the third day of monitoring and revealed that
      voiding behavior is impacted by routine cage changes and time of day.
      CONCLUSIONS: Together these results identify housing and husbandry practices that
      influence male voiding behaviors in the spontaneous void spot assay and will
      inform voiding behavior analyses conducted with male C57Bl/6J mice.

PMID- 25394277
TI  - Dialysis headache in patients undergoing peritoneal dialysis and hemodialysis.
AB  - OBJECTIVES: Headache is among most frequently encountered neurological symptom
      during hemodialysis (HD), but still under investigated in peritoneal dialysis
      (PD) patients. The aim of this study was to assess the incidence and clinical
      characteristics of dialysis headache (DH) in HD and PD patients. MATERIAL AND
      METHODS: A total of 409 patients (91 on PD and 318 on HD) were interviewed using
      a structured questionnaire, designed according to the diagnostic criteria of the
      International Headache Classification of Headache Disorders from 2004. Patients
      with DH underwent a thorough neurological examination. RESULTS: DH was reported
      by 21 (6.6%) HD patients and 0 PD patients. PD patients had significantly lower
      serum sodium, potassium, calcium, phosphate, urea and creatinine, calcium
      phosphate product, and diastolic blood pressure than HD patients. HD patients had
      significantly lower hemoglobin compared to PD patients. Primary renal disease was
      mostly parenchymal in HD patients, and vascular in PD patients. DH appeared more
      frequently in men, mostly during the third hour of HD. It lasted less than four
      hours, was bilateral, non-pulsating and without associated symptoms. CONCLUSION:
      Biochemical alterations may be implicated in the pathophysiology of DH. Specific
      features of DH might contribute to better understanding of this secondary
      headache disorder.

PMID- 25394278
TI  - Familial versus environmental factors in Balkan endemic nephropathy in Mehedinti
      county, Romania, by means of albuminuria and tubular biomarkers: preliminary
      study.
AB  - INTRODUCTION AND AIMS: Balkan endemic nephropathy (BEN), a regional
      tubulointerstitial kidney disease encountered in South-Eastern Europe, with still
      undefined etiology and inexorable evolution towards end stage renal disease,
      raises the question of the relative contribution of family and environmental
      factors in its etiology. In order to evaluate the intervention of these factors,
      markers of tubular injury have been assessed, this lesion being considered an
      early renal involvement in BEN. METHODS: The paper studies relatives of BEN
      patients currently included in dialysis programmes (for involvement of the family
      factor) and their neighbors (for involvement of environmental factors) and
      analyzes them with regard to tubular injury by means of tubular biomarkers (N
      acetyl-beta-d-glucosaminidase-NAG and alpha-1-microglobulin), and albuminuria. At
      the same time, glomerular filtration rate (GFR) (CKD-EPI) was measured. It is
      considered that, in order to acquire the disease, one should have lived for 20
      years in the BEN area. The relatives have been classified according to this
      criterion. RESULTS: More evident tubular injury was found in the neighbors of BEN
      patients living for more than 20 years in the endemic area, which argues in favor
      of environmental factors. Higher levels of urinary alpha-1-microglobulin and
      albumin in relatives of BEN patients who had been living for more than 20 years
      in the area than in relatives with a residence under 20 years, plead for the same
      hypothesis. GFR was lower in persons who had been living for more than 20 years
      in the BEN area (neighbors and relatives). CONCLUSIONS: Environmental factors
      could be more important in BEN than family factors.

PMID- 25394279
TI  - Towards high water permeability in triazine-framework-based microporous membranes
      for dehydration of ethanol.
AB  - The microstructural evolution of a series of triazine framework-based microporous
      (TFM) membranes under different conditions has been explored in this work. The
      pristine TFM membrane is in situ fabricated in the course of polymer synthesis
      via a facile Bronsted-acid-catalyzed cyclotrimerizaiton reaction. The as
      synthesized polymer exhibits a microporous network with high thermal stability.
      The free volume size of the TFM membranes gradually evolved from a unimodal
      distribution to a bimodal distribution under annealing, as analyzed by positron
      annihilation lifetime spectroscopy (PALS). The emergence of the bimodal
      distribution is probably ascribed to the synergetic effect of quenching and
      thermal cyclization reaction. In addition, the fractional free volume (FFV) of
      the membranes presents a concave trend with increasing annealing temperature.
      Vapor sorption tests reveal that the mass transport properties are closely
      associated with the free volume evolution, which provides an optimal condition
      for dehydration of biofuels. A promising separation performance with extremely
      high water permeability has been attained for dehydration of an 85 wt % ethanol
      aqueous solution at 45  degrees C. The study on the free volume evolution of the
      TFM membranes may provide useful insights about the microstructure and mass
      transport behavior of the microporous polymeric materials. 

PMID- 25394280
TI  - IgG1 adsorption to siliconized glass vials-influence of pH, ionic strength, and
      nonionic surfactants.
AB  - In this study, the adsorption of an IgG1 antibody to siliconized vials was
      investigated with focus on the formulation parameters pH, ionic strength, and
      nonionic surfactants. Electrophoretic mobility measurements were performed to
      investigate the charge characteristics of protein and siliconized glass particles
      at different pH values. Calculation of the electrokinetic charge density allowed
      further insight into the energetic conditions in the protein-sorbent interface.
      Maximum adsorption of IgG1 was found at acidic pH values and could be correlated
      with energetically favorable minimal ion incorporation into the interface. The
      importance of electrostatic interactions for IgG1 adsorption at acidic pH values
      was also confirmed by the efficient adsorption reduction at decreased solution
      ionic strength. A second adsorption maximum around the pI of the protein was
      assigned to hydrophobic interactions with the siliconized surface. Addition of
      the nonionic surfactants poloxamer 188 or polysorbate 80 resulted in almost
      complete suppression of adsorption at pH 7.2, and a strong but less efficient
      effect at pH 4 on siliconized glass vials. This adsorption suppression was much
      less pronounced on borosilicate glass vials. From these results, it can be
      concluded that electrostatic interactions contribute substantially to IgG1
      adsorption to siliconized glass vials especially at acidic formulation pH.

PMID- 25394281
TI  - Ionic-liquid-based, manual-shaking- and ultrasound-assisted, surfactant-enhanced
      emulsification microextraction for the determination of three fungicide residues
      in juice samples.
AB  - A novel manual-shaking- and ultrasound-assisted surfactant-enhanced
      emulsification microextraction method was developed for the determination of
      three fungicides in juice samples. In this method, the ionic liquid, 1-ethyl-3
      methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, instead of a volatile
      organic solvent was used as the extraction solvent. The surfactant, NP-10, was
      used as an emulsifier to enhance the dispersion of the water-immiscible ionic
      liquid into an aqueous phase, which accelerated the mass transfer of the
      analytes. Organic dispersive solvent typically required in common dispersive
      liquid-liquid microextraction methods was not necessary. In addition, manual
      shaking for 15 s before ultrasound to preliminarily mix the extraction solvent
      and the aqueous sample could greatly shorten the time for dispersing the ionic
      liquid into aqueous solution by ultrasound irradiation. Several experimental
      parameters affecting the extraction efficiency, including type and volume of
      extraction solvent, type and concentration of surfactant, extraction time, and
      pH, were optimized. Under the optimized conditions, good linearity with the
      correlation coefficients (gamma) higher than 0.9986 and high sensitivity with the
      limit of detection ranging from 0.4 to 1.6 MUg/L were obtained. The average
      recoveries ranged from 61.4 to 86.0% for spiked juice, with relative standard
      deviations from 1.8 to 9.7%. The proposed method was demonstrated to be a simple,
      fast, and efficient method for the analysis of the target fungicides in juice
      samples. 

PMID- 25394282
TI  - Understanding cage effects in imidazolium ionic liquids by 129Xe NMR: MD
      simulations and relativistic DFT calculations.
AB  - (129)Xe NMR has been recently employed to probe the local structure of ionic
      liquids (ILs). However, no theoretical investigation has been yet reported
      addressing the problem of the dependence of the chemical shift of xenon on the
      cage structure of the IL. Therefore, we present here a study of the chemical
      shift of (129)Xe in two ionic liquids, [bmim][Cl] and [bmim][PF6], by a
      combination of classical MD simulations and relativistic DFT calculations of the
      xenon shielding constant. The bulk structure of the two ILs is investigated by
      means of the radial distribution functions, paying special attention to the local
      structure, volume, and charge distribution of the cage surrounding the xenon
      atom. Relativistic DFT calculations, based on the ZORA formalism, on clusters
      extracted from the trajectory files of the two systems, yield an average relative
      chemical shift in good agreement with the experimental data. Our results
      demonstrate the importance of the cage volume and the average charge surrounding
      the xenon nucleus in the IL cage as the factors determining the effective
      shielding. 

PMID- 25394283
TI  - Gene delivery targeted to oligodendrocytes using a lentiviral vector.
AB  - BACKGROUND: Most leukodystrophies result from mutations in genes expressed in
      oligodendrocytes that may cause autonomous loss of function of cell structural
      proteins. Therefore, effective gene delivery to oligodendrocytes is necessary to
      develop future treatments. MATERIALS: To achieve this, we cloned a lentiviral
      vector in which the enhanced green fluorescent protein (EGFP) expression was
      driven by the oligodendrocyte specific 2,3-cyclic nucleotide 3-phosphodiesterase
      promoter. The vector was inserted into C57BL/6 neonatal mouse brain by combined
      intraventricular and parenchymal injections. RESULTS: Assessment of EGFP
      expression revealed a widespread distribution, specifically in cells of the
      oligodendrocyte linage, starting from postnatal day 6 (P6) in the subventricular
      zone and spreading through migrating oligodendrocyte precursors. By P30, it was
      detectable throughout the brain and persisted for at least 3 months, showing an
      increase both in the number of expressing cells and in intensity over time. EGFP
      expression was restricted to oligodendrocyte linage cells. On average, 20.3 +/-
      2.56% of all oligodendrocytes in different central nervous system areas were EGFP
      positive, with regional variations. CONCLUSIONS: Lentiviral gene delivery using
      an oligodendrocyte-specific promoter may achieve widespread and long-lasting
      expression selectively in oligodendrocytes, offering a possibility for gene
      therapy in certain leukodystrophies, although the relatively low rates of
      oligodendrocyte transduction are a limitation that remains to be overcome.

PMID- 25394284
TI  - Silver-free activation of ligated gold(I) chlorides: the use of [Me3NB12Cl11]- as
      a weakly coordinating anion in homogeneous gold catalysis.
AB  - Phosphane and N-heterocyclic carbene ligated gold(I) chlorides can be effectively
      activated by Na[Me3NB12Cl11] (1) under silver-free conditions. This activation
      method with a weakly coordinating closo-dodecaborate anion was shown to be
      suitable for a large variety of reactions known to be catalyzed by homogeneous
      gold species, ranging from carbocyclizations to heterocyclizations. Additionally,
      the capability of 1 in a previously unknown conversion of 5-silyloxy-1,6
      allenynes was demonstrated.

PMID- 25394285
TI  - Activation barriers in the growth of molecular clusters derived from sulfuric
      acid and ammonia.
AB  - Unraveling the chemical mechanism of atmospheric new particle formation (NPF) has
      important implications for the broader understanding of the role of aerosols in
      global climate. We present computational results of the transition states and
      activation barriers for growth of atmospherically relevant positively charged
      molecular clusters containing ammonia and sulfuric acid. Sulfuric acid uptake
      onto the investigated clusters has a small activation free-energy barrier,
      consistent with nearly collision-limited uptake. Ammonia uptake requires
      significant reorganization of ions in the preexisting cluster, which yields an
      activation barrier on the order of 29-53 kJ/mol for the investigated clusters.
      For this reason, ammonia uptake onto positively charged clusters may be too slow
      for cluster growth to proceed by the currently accepted mechanism of stepwise
      addition of sulfuric acid followed by ammonia. The results presented here may
      have important implications for modeling atmospheric NPF and nanoparticle growth,
      which typically does not consider an activation barrier along the growth pathway
      and usually assumes collision-limited molecular uptake. 

PMID- 25394286
TI  - Dairy Products and Health: Recent Insights.
AB  - Milk, cheese, yogurt, and other dairy products have long been known to provide
      good nutrition. Major healthful contributors to the diets of many people include
      the protein, minerals, vitamins, and fatty acids present in milk. Recent studies
      have shown that consumption of dairy products appears to be beneficial in muscle
      building, lowering blood pressure and low-density lipoprotein cholesterol, and
      preventing tooth decay, diabetes, cancer, and obesity. Additional benefits might
      be provided by organic milk and by probiotic microorganisms using milk products
      as a vehicle. New research on dairy products and nutrition will improve our
      understanding of the connections between these products, the bioactive compounds
      in them, and their effects on the human body. 

PMID- 25394287
TI  - Molybdenum complex with bulky chelates as a functional model for molybdenum
      oxidases.
AB  - The novel bulky Schiff base chelate ligand [(4,5-diisopropyl-1H-pyrrole-2
      yl)methylene]-4-(tert-butyl)aniline ((iPr2)HL) bearing two isopropyl groups close
      to the pyrrole nitrogen atom reacts with MoCl2(dme)O2 (dme = 1,2-dimethoxyethane)
      to give the sterically congested complex Mo(VI)((iPr2)L)2O2 ((iPr2)1; OC-6-4-4
      configuration). In spite of the increased steric shielding of the [MoO2] unit
      (iPr2)1 is active in oxygen-atom transfer to PMe3 and PPh3 to give OPMe3 and
      OPPh3, respectively. Because of the increased steric bulk of the chelate ligand,
      formation of dinuclear complexes [Mo(V)((iPr2)L)2O]2(MU-O) ((iPr2)3) by
      comportionation is effectively prevented in contrast to the highly favored
      formation of [Mo(V)((H2)L)2O]2(MU-O) ((H2)3) with the less bulky ligand (H2)HL.
      Instead, the smaller PMe3 ligand coordinates to the resulting pentacoordinate
      intermediate Mo(IV)((iPr2)L)2O ((iPr2)5), giving the hexacoordinate complex
      Mo(IV)((iPr2)L)2O(PMe3) ((iPr2)2) with OC-6-3-3 configuration. The larger
      potential ligands PPh3 and OPPh3 are only able to weakly coordinate to (iPr2)5,
      giving labile and sensitive Mo(IV)((iPr2)L)2O(L) complexes ((iPr2)6, L = PPh3;
      (iPr2)7, L = OPPh3). Traces of water and dioxygen in solutions of (iPr2)6/(iPr2)7
      yield the di(MU-oxido) complex [Mo(V)((iPr2)L)O]2(MU-O)2 ((iPr2)4) with reduced
      steric congestion due to dissociation of the bulky chelate ligands. According to
      electron paramagnetic resonance studies, the much more strongly bound small PMe3
      ligand in (iPr2)2 can be slowly liberated by one-electron oxidation to Mo(V),
      with Ag(+) leaving a free coordination site at Mo(V). Hence, essentially
      pentacoordinate Mo(IV) and Mo(V) complexes are accessible as a result of the
      increased steric bulk. 

PMID- 25394288
TI  - Anaemia in chronic obstructive pulmonary disease: an insight into its prevalence
      and pathophysiology.
AB  - Chronic obstructive pulmonary disease (COPD) is a major health problem, with
      increasing morbidity and mortality. There is a growing literature regarding the
      extra-pulmonary manifestations of COPD, which can have a significant impact on
      symptom burden and disease progression. Anaemia is one of the more recently
      identified co-morbidities, with a prevalence that varies between 4.9% and 38%
      depending on patient characteristics and the diagnostic criteria used. Systemic
      inflammation seems to be an important factor for its establishment and repeated
      bursts of inflammatory mediators during COPD exacerbations could further inhibit
      erythropoiesis. However, renal impairment, malnutrition, low testosterone levels,
      growth hormone level abnormalities, oxygen supplementation, theophylline
      treatment, inhibition of angiotensin-converting enzyme and aging itself are
      additional factors that could be associated with the development of anaemia. The
      present review evaluates the published literature on the prevalence and
      significance of anaemia in COPD. Moreover, it attempts to elucidate the reasons
      for the high variability reported and investigates the complex pathophysiology
      underlying the development of anaemia in these patients. 

PMID- 25394289
TI  - Pound the alarm: danger signals in rheumatic diseases.
AB  - Damage-associated molecular patterns (DAMPs) are chemically heterogeneous
      endogenous host molecules rapidly released from damaged or dying cells that
      incite a sterile inflammatory response mediated via pattern recognition receptors
      (PRRs). The sources of DAMPs are dead or dying cells or the extracellular matrix
      and can signal through the PRRs, the Toll-like receptors or cytosolic Nod-like
      receptors, culminating in nuclear factor kappaB (NF-kappaB) activation and pro
      inflammatory cytokine secretion. Together, these molecules are involved in
      sterile inflammation and many are associated with rheumatic autoimmune diseases
      such as rheumatoid arthritis, systemic lupus erythromatosus, psoriatic arthritis
      and systemic sclerosis. These diseases are associated with inflammation and many
      danger signals are found in sites of sterile inflammation and mediate
      inflammation. The present review examines the role of DAMPs in rheumatic
      conditions and suggests avenues for their therapeutic modulation. 

PMID- 25394290
TI  - Hydrogen sulfide: an old gas with new cardioprotective effects.
AB  - Diabetic cardiovascular complications are reaching epidemic proportions and the
      risk of HF (heart failure) is increased 2-3-fold by diabetes mellitus. H2S
      (hydrogen sulfide) is emerging as a new gaseous signalling molecule in the
      cardiovascular system which possesses multifactorial effects on various
      intracellular signalling pathways. The proven cardioprotective and vasodilator
      activities of H2S warrant a detailed investigation into its role in diabetic
      cardiomyopathy. In the present issue of Clinical Science, Zhou et al. demonstrate
      an important therapeutic potential of the H2S pathway in diabetic cardiomyopathy.

PMID- 25394291
TI  - Hydrogen sulfide attenuates the development of diabetic cardiomyopathy.
AB  - There is growing evidence that H2S has beneficial effects in treatment of various
      cardiovascular diseases. However, it remains unclear whether H2S can attenuate
      the development of diabetic cardiomyopathy (DCM). The present study was designed
      to investigate the protective effects of H2S against DCM. Diabetic rats were
      induced by intraperitoneal injection of streptozotocin and administered with the
      H2S donor sodium hydrosulfide (NaHS) for 16 weeks. Neonatal rat cardiomyocytes
      (NRCMs) transfected with nuclear factor erythroid 2-related factor 2 (Nrf2)
      specific siRNA or pre-treated with SP600125, SB203580 or LY294002 prior to high
      glucose exposure were used to confirm the involvement of Nrf2/antioxidant
      response element (ARE), mitogen-activated protein kinases (MAPKs) and
      phosphoinositide 3-kinase (PI3K)/Akt signalling pathways in the protective
      effects of H2S. The echocardiographical and histopathological data indicated that
      H2S improved left ventricular function and prevented cardiac hypertrophy and
      myocardial fibrosis in diabetic rats. H2S was also found to attenuate
      hyperglycaemia-induced inflammation, oxidative stress and apoptosis in the
      cardiac tissue. In addition, H2S could activate the Nrf2/ARE signalling pathway
      and up-regulate the expression of antioxidant proteins haem oxygenase-1 (HO-1)
      and NAD(P)H: quinone oxidoreductase 1 (NQO1) in the diabetic myocardium.
      Moreover, H2S was found to reduce high glucose-induced apoptosis both in vitro
      and in vivo by inhibiting c-Jun N-terminal kinase (JNK) and p38 MAPK pathways and
      activating PI3K/Akt signalling. In conclusion, our study demonstrates that H2S
      alleviates the development of DCM via attenuation of inflammation, oxidative
      stress and apoptosis.

PMID- 25394292
TI  - Essential regional nerve blocks for the dermatologist: Part 2.
AB  - Following on from Part 1 of the series (regional nerve blocks for the face and
      scalp), we guide the clinician through the anatomy and cutaneous innervation of
      the digits, wrist and ankle, providing a practical step-by-step guide to regional
      nerve blockade of these areas. 

PMID- 25394293
TI  - Cutaneous drug eruption induced by antihistamines.
AB  - Topical application of antihistamines commonly leads to sensitization for
      patients, but systemic administration of antihistamines rarely induces allergic
      hypersensitivity, which is mainly linked to phenothiazine-derived and piperazine
      derived compounds. We report a 70-year-old woman whose medical history included
      lichen planus, and who was referred by the dermatology department of our hospital
      for suspected allergy to corticosteroids. The reason for referral was that on the
      fourth day of treatment with prednisone and hydroxyzine, the patient presented a
      bilateral highly pruritic palmar erythema that evolved to a generalized
      morbilliform rash with subsequent complete desquamation. At a later time, she
      took cetirizine for a cold, and developed palmar erythema and desquamation. Skin
      tests (prick and intradermal tests) were performed with steroids, and patch tests
      (read after 48 and 96 h) with corticosteroids and antihistamines. Controlled oral
      challenge tests were performed with prednisone and with an alternative
      antihistamine. Skin tests were negative for all corticosteroids. Patch tests were
      negative for all corticosteroids, but the antihistamine test was positive for
      hydroxyzine. Oral challenge with prednisone and dexchlorpheniramine was negative.
      The patient was diagnosed with cutaneous drug eruption from hydroxyzine and
      cetirizine. We consider it is important to assess every patient whose skin
      condition worsens after treatment with antihistamines, especially hydroxyzine,
      because it is known that antihistamines are often not recognised as the culprit
      in cases of cutaneous eruption. 

PMID- 25394294
TI  - Force-production asymmetry in male and female athletes of differing strength
      levels.
AB  - The purpose of this investigation was to determine the existence of bilateral
      strength and force-production asymmetry and evaluate possible differences based
      on sex, as well as strength level. Asymmetry was assessed during weight
      distribution (WtD) testing, unloaded and lightly loaded static- (SJ) and
      countermovement-jump (CMJ) testing, and isometric midthigh-pull (IMTP) strength
      testing. Subjects included 63 athletes (31 male, 32 female) for WtD, SJ, and CMJ
      tests, while 129 athletes (64 male, 65 female) participated in IMTP testing.
      Independent-samples t tests were used to determine possible differences in
      asymmetry magnitude between males and females, as well as between strong and weak
      athletes. Cohen d effect-size (ES) estimates were also used to estimate
      difference magnitudes. Statistically different asymmetry levels with moderate to
      strong ESs were seen between males and females in WtD, 0-kg SJ (peak force [PF]),
      20-kg SJ (peak power [PP]), 0-kg CMJ (PF, PP, net impulse), and 20-kg CMJ (PF),
      but no statistical differences were observed in IMTP variables. Dividing the
      sample into strong and weak groups produced statistically significant differences
      with strong ES estimates in IMTP PF and rate of force development, and many ESs
      in jump symmetry variables increased. The results of this investigation indicate
      that females may be more prone to producing forces asymmetrically than males
      during WtD and jumping tasks. Similarly, weaker athletes displayed more asymmetry
      than stronger athletes. This may indicate that absolute strength may play a
      larger role in influencing asymmetry magnitude than sex. 

PMID- 25394296
TI  - Diagnostic and therapeutic utility of SpyGlass((r)) peroral cholangioscopy in
      intraductal biliary disease: single-center, retrospective, cohort study.
AB  - BACKGROUND AND AIM: SpyGlass(r) cholangiopancreatoscopy system has shown early
      success in aiding diagnosis and management of pancreaticobiliary diseases. We
      aimed to assess the technical success, clinical success, diagnostic yield,
      therapeutic yield, and safety of the SpyGlass(r) system at a single institution.
      METHODS: A retrospective, single-center review of consecutive patients who
      underwent endoscopic retrograde cholangiopancreatography with SpyGlass(r) between
      January 2008 and August 2013 for a variety of indications. Technical success was
      defined as the procedure being completed as planned. Clinical success was defined
      as a successful outcome using diagnostic, clinical, laboratory, or imaging
      evidence. RESULTS: SpyGlass(r) cholangioscopy was carried out in 88 patients (49
      females, mean age 56.9 +/- 15.5 years). Indications were diagnostic in 67 and
      therapeutic in 21. Overall, technical success was seen in 87.5% and clinical
      success in 77.3%. Thirty-nine patients with indeterminate biliary stricture had
      technical and clinical success rates of 92.3% and 74.4%, respectively. In this
      subgroup, malignancy was ultimately diagnosed in 13 with 12 patients diagnosed by
      SpyGlass(r) and confirmed by surgical specimens in 12/12 cases; positive
      predictive value 100%). In the 23 remaining patients with indeterminate biliary
      strictures, one was later found to have malignancy (negative predictive value
      95.8%) after 1 year of follow up. In the 13 therapeutic cases of stone removal,
      technical and clinical success was seen in 77.0% for both. Overall, adverse
      events were seen in 15.9%. CONCLUSIONS: SpyGlass(r) demonstrated acceptable
      technical and clinical success rates in both diagnostic and therapeutic
      procedures. In particular, it allows for an accurate rate of diagnosis of
      indeterminate biliary strictures.

PMID- 25394295
TI  - Bupivacaine mandibular nerve block affects intraoperative blood pressure and
      heart rate in a Yucatan miniature swine mandibular condylectomy model: a pilot
      study.
AB  - PURPOSE/AIM: The primary objective was to evaluate the effect of a bupivacaine
      mandibular nerve block on intraoperative blood pressure (BP) and heart rate (HR)
      in response to surgical stimulation and the need for systemic analgesics
      postoperatively. We hypothesized that a mandibular nerve block would decrease the
      need for systemic analgesics both intraoperatively and postoperatively. MATERIALS
      AND METHODS: Fourteen adult male Yucatan pigs were purchased. Pigs were
      chemically restrained with ketamine, midazolam, and dexmedetomidine and
      anesthesia was maintained with isoflurane inhalant anesthesia. Pigs were
      randomized to receive a mandibular block with either bupivacaine (bupivacaine
      group) or saline (control group). A nerve stimulator was used for administration
      of the block with observation of masseter muscle twitch to indicate the injection
      site. Invasive BP and HR were measured with the aid of an arterial catheter in
      eight pigs. A rescue analgesic protocol consisting of fentanyl and lidocaine was
      administered if HR or BP values increased 20% from baseline. Postoperative pain
      was quantified with a customized ethogram. HR and BP were evaluated at base line,
      pre-rescue, 10 and 20 min post-rescue. RESULTS: Pre-rescue mean BP was
      significantly increased (p = .001) for the bupivacaine group. Mean intraoperative
      HR was significantly lower (p = .044) in the bupivacaine versus saline group. All
      other parameters were not significant. CONCLUSION: Addition of a mandibular nerve
      block to the anesthetic regimen in the miniature pig condylectomy model may
      improve variations in intraoperative BP and HR. This study establishes the
      foundation for future studies with larger animal numbers to confirm these
      preliminary findings.

PMID- 25394297
TI  - Prenatal Exposure to Angiotensin II Receptor Blockers and Hemodynamic Effects on
      the Newborn.
AB  - Angiotensin II receptor blockers (ARBs) are potent antihypertensive agents that
      block the renin angiotensin aldosterone system (RAS). Their use in pregnancy may
      cause malformations, oligoanuria, hypotension, and death. Hypotension is observed
      up to 15% of cases and is described as refractory to volume and inotropic
      support, although its pathophysiology is unknown. We present a case of prenatal
      exposure to ARBs in order to characterize the hemodynamic compromise in the
      newborn, help in decision-making, and guide the therapeutic approach to these
      patients. 

PMID- 25394298
TI  - Laminations and microgranule formation in pediatric glomerular basement
      membranes.
AB  - Glomerular basement membrane (GBM) splitting, laminations, and microgranular
      formation are classically encountered with Alport disease, but can be found in
      other glomerular diseases. We found moderate to marked GBM
      laminations/microgranular formations in 51 of 724 (7%) pediatric diagnostic renal
      biopsies. These included 12 Alport disease, 12 thin basement membrane disease
      (TBM), 13 mesangial hypercellularity (MH), 6 focal segmental glomerulosclerosis
      (FSGS), and 8 other diseases. Follow-up demonstrated progression in most of the
      Alport disease and FSGS, as expected, but also in 40% of TBM and 30% of MH.
      Basement membrane laminations/microgranular formations are not specific for
      Alport disease, may represent a non-specific injury, and may herald a progressive
      clinical course. 

PMID- 25394299
TI  - Variations in lipid screening frequency in family medicine patients with
      cardiovascular risk factors.
AB  - RATIONALE, AIMS AND OBJECTIVES: This study was undertaken to assess the frequency
      of lipid screening in comparison with the United States Preventive Services Task
      Force guideline in a sample of family medicine patients. In addition, we sought
      to determine the association between testing frequency and achievement of lipid
      targets. METHODS: A random sample was extracted from 271 patients from among all
      patients cared for in our Department of Family Medicine for whom lipid screening
      was ordered from March to September 2012 and who had >=2 well-defined
      cardiovascular risk factors. Lipid testing frequency was classified in three
      ways: semi-annual or less often (0-12 tests over 6 years), annual or less often
      (0-6 tests), or biennial (0-3 tests). RESULTS: Multiple logistic regression
      analysis revealed that the predictors of lipid screening more often than semi
      annually were age >=60 years [odds ratio (OR) = 3.7] and diabetes mellitus (DM)
      (OR = 30.6). Predictors of screening more often than annually were DM (OR = 4.3),
      hypertension (OR = 2.1), family history of premature coronary artery disease (OR
      = 5.6) and statin treatment (OR = 3.5). Lipid goal attainment was not associated
      with testing frequency except with regard to low-density lipoprotein levels (P =
      0.043, P < 0.001, P = 0.005, by semi-annual, annual and biennial, respectively)
      and total cholesterol levels (P = 0.015, P = 0.025 by semi-annual and annual,
      respectively). CONCLUSIONS: Questionable high frequency of lipid testing was
      detected even when the more conservative approach of annual monitoring was
      assumed. Frequency of testing was not associated with goal attainment for most
      parameters. Physicians should request the lipid testing based on overall risk
      assessment and person variability in accordance with published guidelines.

PMID- 25394300
TI  - LEF-1 is frequently expressed in colorectal carcinoma and not in other
      gastrointestinal tract adenocarcinomas: an immunohistochemical survey of 602
      gastrointestinal tract neoplasms.
AB  - LEF-1 is a DNA-binding protein that interacts with beta-catenin and activates Wnt
      responsive target genes. We analyzed the immunohistochemical expression of LEF-1
      in 602 gastrointestinal and pancreatobiliary neoplasms in an attempt to (1)
      investigate the utility of LEF-1 immunohistochemistry as an ancillary marker in
      gastrointestinal/pancreatobiliary neoplasia, and (2) to perform a
      clinicopathologic and survival analysis of colorectal carcinoma stratified by LEF
      1 expression. LEF-1 nuclear positivity was frequently identified in colorectal
      carcinoma (89/241, 37%) and only infrequently identified in other neoplasms: 11%
      esophagus/esophagogastric adenocarcinomas, 7% gastric adenocarcinomas, 1%
      pancreatic ductal adenocarcinomas, 4% pancreatic intraductal papillary mucinous
      neoplasms, and in no cases of appendiceal mucinous neoplasms or pancreatic
      mucinous cystic neoplasms. LEF-1 expression was identified in 35% of colorectal
      carcinomas that lacked CK20 and CDX2 expression. In colorectal carcinomas, LEF-1
      positive tumors more frequently harbored KRAS mutations compared with LEF-1
      negative tumors (39% vs. 16%, P=0.005). Patients with moderate/strong LEF-1
      positive colorectal carcinoma had a trend of worse overall survival compared with
      patients with colorectal carcinomas with weak/negative LEF-1 expression (5 y
      overall survival, 31% vs. 47%, P=0.15). In conclusion, LEF-1 is most commonly
      expressed in colorectal carcinoma and infrequently observed in the upper
      gastrointestinal tract and pancreatic adenocarcinoma. LEF-1 Immunohistochemistry
      may be especially useful as an ancillary diagnostic marker in colorectal
      carcinomas, which lack the expression of both CK20 and CDX2. LEF-1 expression is
      associated with the presence of KRAS mutations and may have prognostic value as a
      trend of worse overall survival is seen in patients with LEF-1-positive
      colorectal carcinoma. 

PMID- 25394301
TI  - Total synthesis of Deoxy-solomonamide B by mimicking biogenesis.
AB  - A total synthesis of Deoxy-solomonamide B was accomplished starting from
      tryptophan in an efficient manner by mimicking the proposed biogenetic route. The
      present synthesis utilizes a crotylation, oxidative cleavage of the indole
      moiety, and macrolactamization as key steps. The use of the indole nucleus as a
      masked anthranilic acid unit paves the way for the easy synthesis of related
      macrocycles and natural products where the ortho-acyl aniline moiety is embedded
      into them, which otherwise is difficult to synthesize. 

PMID- 25394302
TI  - The significance for epidemiological studies anti-measles antibody detection
      examined by enzyme immunoassay (EIA) and plaque reduction neutralization test
      (PRNT).
AB  - The paper discusses the role of anti-measles antibodies for protection and
      significance for epidemiological studies determination of antibodies by different
      serological methods. The comparison of anti-measles virus antibodies levels
      measured by enzyme immunoassay (EIA) and Plaque Reduction Neutralization Test
      (PRNT) was described. It was found that the 200 mIU/ml of anti-measles activity
      measured by PRNT (level protection against symp- tomatic disease) is equivalent
      of 636 mIU/ml measured by EIA (Enzygnost(r)Anti-Measles Virus/IgG, Simens).

PMID- 25394304
TI  - Standards of hepatitis C treatment. Recommendations of Polish Group of Experts-
      2014.

PMID- 25394303
TI  - Lyme disease with effusion either in hip or knee in children from Podlaskie
      region treated in clinic in 2004-2010.
AB  - OBJECTIVES: Lyme disease (LB) relatively commonly causes arthritis among
      patients, especially in LB endemic area. The aim of the study was to analyze the
      prevalence of LB in children with hip and knee effusion in the North Eastern
      region of Poland. Conclusions from our study should justify the need of taking
      into account LB in the diagnosis of hip or knee effusion in children. MATERIALS
      AND METHODS: The medical records of 321 children, aged 2-18 years, with synovitis
      of the hip or knee were reviewed. RESULTS: In 273 cases with hip effusion: 32
      (11.72%) patients were diagnosed with LB, 233 (85.74%) with transient arthritis,
      6 (2.19%) with purulent arthritis, and 2 (0.73%) with juvenile idiopathic
      arthritis. In 48 cases with knee effusion: 12 (25%) patients were diagnosed with
      Lyme arthritis, 24 (50%) with transient arthritis, 5 (10.42%) with reactive
      arthritis, 4 (8.33%) with juvenile idiopathic arthritis, and 3 (6.25%) with
      purulent arthritis. CONCLUSIONS: The high prevalence of LB in children with hip
      or knee effusion in endemic areas suggests the need of diagnostics also for LB in
      all patients presenting with acute monoarticular arthritis. Antibiotic treatment
      results in complete recovery.

PMID- 25394305
TI  - Effect of nanostructures on the meniscus shape and disjoining pressure of
      ultrathin liquid film.
AB  - The stability of thin liquid films on nanostructured surfaces is important but
      poorly understood. Here, we develop a general model of the meniscus shape and
      disjoining pressure for thin liquid films on nanostructured surfaces based on the
      minimization of the free energy and the Derjaguin approximation. This model is
      then compared with molecular dynamics simulations for a water-gold system with
      triangular and square nanostructures of varying depth and film thickness,
      demonstrating the robustness of the analytical model. 

PMID- 25394306
TI  - Diagnosis of vocal fold paresis: current opinion and practice.
AB  - OBJECTIVES/HYPOTHESIS: No accepted standard exists for the diagnosis of vocal
      fold paresis (VFP). Laryngeal specialists are surveyed to establish expert
      opinion on diagnostic methodology and criteria. STUDY DESIGN: Cross-sectional
      survey. METHODS: Questionnaires were distributed at laryngology conferences in
      fall 2013. Responses were collated anonymously and subjected to cross-tabulated
      data analysis. RESULTS: Fifty-eight responses completed by posttraining
      physicians whose practice focused in laryngology >= 75% were analyzed. One (1.7%)
      relied principally on laryngeal electromyography, one (1.7%) on history, 10 (17%)
      on laryngoscopy, and 42 (72%) on strobovideolaryngoscopy for diagnosis. Only 12
      (21%) performed laryngeal electromyography on > 50% of vocal fold paresis
      patients. Laryngeal electromyography sensitivity was considered moderate (61 +/-
      3.7%, sigma = 28). Laryngoscopic/stroboscopic findings considered to have the
      strongest positive predictive value for VFP were slow/sluggish vocal fold motion
      (75 +/- 3.0%, sigma = 23), decreased adduction (67 +/- 3.5%, sigma = 27),
      decreased abduction (65 +/- 3.4%, sigma = 26), and decreased vocal fold tone (61
      +/- 3.5%, sigma = 26). Asymmetric mucosal wave amplitude (52 +/- 4.2%, sigma =
      32), asymmetric mucosal wave phase (60 +/- 4.1%, sigma = 31), hemilaryngeal
      atrophy (60 +/- 4.0%, sigma = 31), and asymmetric mucosal wave frequency (49 +/-
      4.0%, sigma = 30) generated greatest disagreement. CONCLUSIONS: Surveyed expert
      laryngologists diagnose vocal fold paresis predominantly on stroboscopic
      examination. Gross motion abnormalities had the highest positive predictive
      value. Laryngeal electromyography was infrequently used to assess for vocal fold
      paresis.

PMID- 25394307
TI  - Blocking CD40-TRAF6 interactions by small-molecule inhibitor 6860766 ameliorates
      the complications of diet-induced obesity in mice.
AB  - BACKGROUND: Immune processes contribute to the development of obesity and its
      complications, such as insulin resistance, type 2 diabetes mellitus and
      cardiovascular disease. Approaches that target the inflammatory response are
      promising therapeutic strategies for obesity. In this context, we recently
      demonstrated that the interaction between the costimulatory protein CD40 and its
      downstream adaptor protein tumor necrosis factor receptor-associated factor 6
      (TRAF6) promotes adipose tissue inflammation, insulin resistance and hepatic
      steatosis in mice in the course of diet-induced obesity (DIO). METHODS: Here we
      evaluated the effects of a small-molecule inhibitor (SMI) of the CD40-TRAF6
      interaction, SMI 6860766, on the development of obesity and its complications in
      mice that were subjected to DIO. RESULTS: Treatment with SMI 6860766 did not
      result in differences in weight gain, but improved glucose tolerance. Moreover,
      SMI 6860766 treatment reduced the amount of CD45(+) leucocytes in the epididymal
      adipose tissue by 69%. Especially, the number of adipose tissue CD4(+) and CD8(+)
      T cells, as well as macrophages, was significantly decreased. CONCLUSIONS: Our
      results indicate that small-molecule-mediated inhibition of the CD40-TRAF6
      interaction is a promising therapeutic strategy for the treatment of metabolic
      complications of obesity by improving glucose tolerance, by reducing the
      accumulation of immune cells to the adipose tissue and by skewing of the immune
      response towards a more anti-inflammatory profile.

PMID- 25394309
TI  - A trip to remember, with strings attached: researchers begin sorting through the
      tangled ethical and legal implications of medical tourism.

PMID- 25394308
TI  - Energy balance measurement: when something is not better than nothing.
AB  - Energy intake (EI) and physical activity energy expenditure (PAEE) are key
      modifiable determinants of energy balance, traditionally assessed by self-report
      despite its repeated demonstration of considerable inaccuracies. We argue here
      that it is time to move from the common view that self-reports of EI and PAEE are
      imperfect, but nevertheless deserving of use, to a view commensurate with the
      evidence that self-reports of EI and PAEE are so poor that they are wholly
      unacceptable for scientific research on EI and PAEE. While new strategies for
      objectively determining energy balance are in their infancy, it is unacceptable
      to use decidedly inaccurate instruments, which may misguide health-care policies,
      future research and clinical judgment. The scientific and medical communities
      should discontinue reliance on self-reported EI and PAEE. Researchers and
      sponsors should develop objective measures of energy balance. 

PMID- 25394310
TI  - Neutrophilic dermatosis: disease mechanism and treatment.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the
      physiopathological and therapeutic aspects of neutrophilic dermatosis, taking
      into account their most frequent associated conditions. RECENT FINDINGS: In
      autoinflammatory syndromes featuring neutrophilic dermatosis, the role of
      interleukin-1 and tumor necrosis factor (TNF)-alpha cytokines in the
      immunopathogenesis of neutrophilic dermatosis has supported their classification
      as autoinflammatory diseases. In malignancy-associated neutrophilic dermatosis,
      the role of the malignant clone in myeloid neoplasms and the role of the
      monoclonal gammopathy and/or of the malignant plasmocyte clone in myeloma have
      been underlined. SUMMARY: Recent insights into neutrophilic dermatosis'
      pathophysiology have encouraged the use of targeted biological therapies for
      their treatment. Although systemic glucocorticoids remain the mainstay of
      treatment for Sweet's syndrome and pyoderma gangrenosum, anti-TNF-alpha is
      becoming the preferred treatment when pyoderma gangrenosum is accompanied by
      inflammatory bowel disease or rheumatoid arthritis. Interleukin-1 receptor
      inhibitor anakinra is a promising therapeutic alternative for refractory Sweet's
      syndrome.

PMID- 25394311
TI  - The role of neutrophils in causing antineutrophil cytoplasmic autoantibody
      associated vasculitis.
AB  - PURPOSE OF REVIEW: Antineutrophil cytoplasmic antibody (ANCA)-activated
      phagocytes cause vasculitis and necrotizing crescentic glomerulonephritis.
      Experimental data support the notion that activation of neutrophils and monocytes
      by ANCA immunoglobulin G with generation of reactive oxygen species,
      degranulation of proteases, and formation of neutrophil extracellular traps play
      a role in tissue injury. RECENT FINDINGS: We discuss novel findings regarding the
      expression of ANCA antigens and the mechanisms involved in myeloid cell
      activation by ANCA immunoglobulin G. The contribution of neutrophil serine
      proteases and their specific role in the generation of interleukin-1beta (IL
      1beta) is highlighted. ANCA-induced reactive oxygen species generation plays an
      important role in downregulating inflammation by inhibition of the inflammasome
      dependent caspase-1 activation and subsequent IL-1beta generation. Neutrophil
      extracellular trap generation by ANCA-activated neutrophils and their potential
      role in the pathogenesis of the disease will be discussed. Lastly, the pathogenic
      role of the complement system will be discussed. SUMMARY: ANCA-induced activation
      of both neutrophils and monocytes is one of the main pathogenic mechanisms
      involved in disease induction. Therefore, a better understanding of the
      fundamental processes involved here are necessary. Specifically, the mechanisms
      involved in IL-1beta generation have been recently identified and could lead to
      better targeted novel therapies.

PMID- 25394312
TI  - Chronic granulomatous disease - conventional treatment vs. hematopoietic stem
      cell transplantation: an update.
AB  - PURPOSE OF REVIEW: We update and summarize the recent findings in conventional
      treatment and hematopoietic stem cell transplantation in chronic granulomatous
      disease (CGD). We also summarize the contemporary view on when hematopoietic stem
      cell transplantation should be the preferred treatment of choice in CGD. RECENT
      FINDINGS: Azole antifungal treatment in CGD has improved survival. With prolonged
      survival, inflammatory complications are an emerging problem in CGD. Several
      studies now present excellent results with stem cell transplantation in severe
      CGD, also with reduced intensity conditioning. SUMMARY: Several lines of evidence
      now suggest that stem cell transplantation should be the preferred treatment of
      choice in severe CGD, if there is an available donor. This should be performed as
      soon as possible to avoid severe sequelae from infection and inflammation.

PMID- 25394314
TI  - Radiological improvements in global sagittal alignment after lumbar decompression
      without fusion.
AB  - STUDY DESIGN: A retrospective, radiographical study. OBJECTIVE: To evaluate short
      term radiological changes in sagittal alignment after lumbar decompression
      without fusion for lumbar canal stenosis. SUMMARY OF BACKGROUND DATA: Although
      the importance of global sagittal balance is underscored recently, little is
      known about the changes in sagittal alignment after lumbar canal decompression.
      METHODS: We retrospectively reviewed 88 patients who underwent lumbar
      decompression without fusion at a single institution between November 2008 and
      May 2013, with a minimum follow-up of 5 months. Standing radiographs at the
      preoperative period and the final follow-up were assessed. Radiological
      parameters included the sagittal vertical axis (SVA), lumbar lordosis (LL),
      pelvic tilt, pelvic incidence (PI), occipital 7th cervical angle, and thoracic
      kyphosis, which were measured by 2 spine surgeons. The Zurich Claudication
      Questionnaire and visual analogue scale scores were obtained to assess the
      patient-based clinical outcomes. RESULTS: Both LL and thoracic kyphosis
      significantly increased postoperatively, whereas SVA, PI-LL (PI minus LL), and
      pelvic tilt significantly decreased (P<0.05). There were no significant
      differences between the preoperative and postoperative occipital 7th cervical
      angle and PI. The amount of increment in LL was greater in patients with small
      preoperative LL. The improvement in SVA was greater in those with a large
      preoperative SVA. The Zurich Claudication Questionnaire and visual analogue scale
      scores showed no significant correlation with the radiological parameters.
      CONCLUSION: Lumbar decompression without fusion can induce a reactive improvement
      in the lumbar and global sagittal alignment even if a sagittal imbalance exists
      preoperatively. LEVEL OF EVIDENCE: 4.

PMID- 25394313
TI  - How methicillin-resistant Staphylococcus aureus evade neutrophil killing.
AB  - PURPOSE OF REVIEW: Methicillin-resistant strains of the important human pathogen
      Staphylococcus aureus pose a significant public health threat in the community,
      as they are easily transmitted, especially prone to cause invasive disease, and
      infect otherwise healthy individuals. The mechanistic basis for the ability of
      these organisms to evade the innate immune responses remains incompletely
      defined. RECENT FINDINGS: The success of pathogens such as S. aureus rests, in
      part, on their capacity to overcome neutrophil-mediated host defense to establish
      infection and cause human disease. S. aureus has the potential to thwart
      effective neutrophil chemotaxis, and phagocytosis, and succeeds in evading
      killing by neutrophils. Furthermore, S. aureus surviving within neutrophils
      promotes neutrophil cytolysis, with release of host-derived molecules that
      promote local inflammation. Here, we provide a brief overview of our
      understanding of the mechanisms by which S. aureus - including methicillin
      resistant S. aureus - avoids neutrophil-mediated host defense and causes disease.
      SUMMARY: Understanding the molecular mechanisms by which S. aureus avoids
      neutrophil-mediated responses and initiates signaling cascades that culminate in
      neutrophil lysis will provide insights prerequisite to the development of novel
      targets for treating staphylococcal infections.

PMID- 25394315
TI  - The association between spinal cord injury and acute myocardial infarction in a
      nationwide population-based cohort study.
AB  - STUDY DESIGN: A spinal cord injury (SCI) retrospective cohort study was derived
      from the National Health Insurance Research Database of Taiwan. OBJECTIVE: We
      evaluated risk of acute myocardial infarction (AMI) in patients newly diagnosed
      with SCI. SUMMARY OF BACKGROUND DATA: According to information of the World
      Health Organization, cardiovascular diseases are the most frequent causes of
      death in patients with SCI compared with those in the general population.
      METHODS: We obtained claims data from the National Health Insurance Research
      Database for this cohort study. The SCI group comprised 22,197 patients with a
      diagnosis of SCI. Case and control patients were based on risk-set sampling in a
      1:4 ratio, and we excluded patients with a prior diagnosis of AMI. Comorbidities
      were categorized as the proportion of prior illnesses in the SCI and non-SCI
      groups. We used the Cox proportion model to explore adjusted hazard ratio (aHR)
      for developing AMI between case and control patients. RESULTS: Patients with SCI
      were significantly more likely to exhibit pre-existing illnesses associated with
      AMI than patients without SCI. Patients with a diagnosis of SCI exhibited
      significantly higher aHRs for developing AMI than patients without SCI (aHR=1.17;
      P<0.05). Patients with SCI, compared with patients without SCI, were associated
      with a subsequent AMI risk (aHR=1.17; P<0.05). Several comorbidities, such as
      cardiovascular disease (aHR=1.29; P<0.05), chronic obstructive pulmonary disease
      (aHR=1.51; P<0.05), hypertension (aHR=1.34; P<0.01), and renal disease (aHR=1.76;
      P<0.05), were associated with an increased AMI risk. Furthermore, T-spine SCI was
      significantly associated with an AMI risk (aHR=1.38; P<0.05). CONCLUSION:
      Patients with as diagnosis of SCI exhibited an increased risk of AMI compared
      with patients without SCI. These findings have broad implications for
      surveillance among patients with SCI, and future studies should evaluate whether
      risk factor modification can decrease AMI risk among patients with SCI. LEVEL OF
      EVIDENCE: 3.

PMID- 25394316
TI  - Reconsidering the Roland-Morris Disability Questionnaire: time for a
      multidimensional framework?
AB  - STUDY DESIGN: Cross-sectional design. OBJECTIVE: To explore (1) the factor
      structure of the Roland-Morris Disability Questionnaire (RMDQ), (2) whether there
      is a dominant factor, and (3) whether the potential factors are unique predictors
      of other aspects related to back pain. SUMMARY OF BACKGROUND DATA: The RMDQ is
      one of the most recommended back-specific questionnaires assessing disability.
      The RMDQ is scored as a unidimensional scale summarizing answers to all 24
      questions (Yes/No) regarding daily life functioning. However, there are
      indications that the scale is multidimensional. METHODS: Patients (n = 457; age,
      18-60 yr) with 8 to 12 weeks of back pain filled in questionnaires assessing
      subjective health complaints, emotional distress, instrumental and emotion
      focused coping, and fear voidance behavior at baseline. A total of 371 patients
      (81.7%) filled in the RMDQ. Exploratory factor analysis was used to examine the
      factor structure of RMDQ items. Multiple regression analyses were used to assess
      whether the derived factors predicted relevant problems in back pain differently.
      RESULTS: Exploratory factor analysis showed indices of model fit for a 3-factor
      solution after removing 2 items because of low prevalence (19 and 24). Two items
      were removed because of cross-loadings and low loadings (2 and 22). No support
      for a dominant factor was found as the 3 factors were only moderately correlated
      (r = 0.34-0.40), and the ratio between the first and second eigenvalue was 2.6,
      not supporting essential unidimensionality. "Symptoms" were the factor that most
      strongly predicted subjective health complaints, whereas "avoidance of activity
      and participation" predicted fear avoidance behavior, instrumental and emotional
      coping. "Limitation in daily activities" did not predict any of these variables.
      CONCLUSION: The main findings of our study are that the RMDQ consists of 3
      independent factors, and not 1 dominant factor as suggested previously. We think
      the time is now ripe to start treating and scoring the RMDQ as a multidimensional
      scale. LEVEL OF EVIDENCE: N/A.

PMID- 25394317
TI  - Effect of indirect neural decompression through oblique lateral interbody fusion
      for degenerative lumbar disease.
AB  - STUDY DESIGN: Prospective consecutive clinical study to assess the decompressive
      benefit and outcome of oblique lateral interbody fusion for lumbar degenerative
      diseases. OBJECTIVE: To evaluate radiologically the effect of interbody
      distraction upon neural patency via an anterolateral retroperitoneal approach for
      the treatment of lumbar degenerative diseases. SUMMARY OF BACKGROUND DATA:
      Traditional treatment for symptomatic lumbar stenosis uses direct posterior
      decompression with or without fusion. Symptoms of radiculopathy and neurological
      claudication may also be alleviated indirectly through restoration of
      intervertebral and foraminal heights and correction of spinal alignment. METHODS:
      Twenty-eight consecutive patients presenting with degenerative conditions that
      included concomitant lumbar stenosis underwent oblique lateral interbody fusion
      combined with percutaneous pedicle screw fixation at 52 lumbar levels without
      neuromonitoring. Magnetic resonance images were obtained successfully for 48 of
      52 levels. The cross-sectional area of the thecal sac (CSA) was measured
      preoperatively and postoperatively on T2-weighted axial magnetic resonance
      images. Differences in CSA were compared, and the relationship between the ratio
      of CSA extension and that of the preoperative CSA was assessed. The change in
      disc height and segmental disc angle were measured. The relationships between
      CSA, disc height, segmental disc angle, and clinical results were assessed by
      correlational analysis. RESULTS: Twenty-eight oblique lateral interbody fusions
      were performed successfully without neural complications. There was clinical
      improvement in all cases. The mean CSA increased from 99.6 mm preoperatively to
      134.3 mm postoperatively (P<0.001). The median CSA extension ratio was 30.2% and
      this correlated inversely with preoperative CSA. Disc height, segmental disc
      angle, and clinical results improved significantly. Multivariate regression
      analysis demonstrated that the preoperative CSA was the only independent factor
      that correlated inversely with the CSA extension ratio (corrected R=0.361;
      P<0.001). CONCLUSION: Spinal stenosis was resolved successfully by indirect
      decompression through a miniopen anterolateral retroperitoneal approach without
      the need for neuromonitoring. LEVEL OF EVIDENCE: 3.

PMID- 25394318
TI  - Predicting the DRAM mZDI using the PROMIS anxiety and depression.
AB  - STUDY DESIGN: Data were collected at a university orthopedic clinic in 2012. The
      final sample consisted of 316 patients. Sample included new and annual follow-up
      adult patients for all operative and nonoperative spine care. Outcome measures
      consisted of the patient-reported outcome measurement information system (PROMIS)
      anxiety 4-item short form (SF-4), the PROMIS depression SF-4, and the distress
      and risk assessment method modified Zung Depression Index (mZDI). OBJECTIVE: The
      objective of this study was to assess whether the PROMIS anxiety 4-item short
      form (anxiety SF-4) or the PROMIS depression SF-4 (depression SF-4) can be used
      in place of the distress and risk assessment method mZDI. SUMMARY OF BACKGROUND
      DATA: Studies comparing the PROMIS short forms with the existing instruments are
      limited. In particular, there is not any published study comparing the PROMIS
      anxiety and depression short forms with the distress and risk assessment method
      mZDI. METHODS: Regression analyses were carried out to predict the mZDI total
      scores from the PROMIS anxiety SF-4 T scores and the PROMIS depression SF-4 T
      scores. Intraclass correlation coefficients were computed on the actual and
      predicted mZDI scores. RESULTS: All 3 instruments were highly correlated with
      each other. The PROMIS anxiety SF-4 and the PROMIS depression SF-4 were both able
      to explain a significant amount of variance in the mZDI. The intraclass
      correlation coefficients for the actual and predicted mZDI scores were high. The
      actual mZDI scores and predicted mZDI scores using either the PROMIS anxiety SF-4
      or the PROMIS depression SF-4 across age and sex were similar. CONCLUSION: This
      study indicates that the PROMIS anxiety SF-4 scores and the depression SF-4
      scores can accurately predict the mZDI scores. The PROMIS anxiety and depression
      short forms can be used as surrogates for the mZDI. LEVEL OF EVIDENCE: 3.

PMID- 25394319
TI  - Comparison of Smith-Petersen osteotomy versus pedicle subtraction osteotomy
      versus anterior-posterior osteotomy types for the correction of cervical spine
      deformities.
AB  - STUDY DESIGN: Retrospective case controlled study. OBJECTIVE: To describe the
      amount of correction obtained with different types of osteotomies in the cervical
      spine when treating cervical deformity. SUMMARY OF BACKGROUND DATA: Although the
      corrective power of various osteotomies in the thoracic and lumbar spine are well
      described, there are no reports in the literature on the corrective capabilities
      of osteotomies in the cervical spine to guide preoperative planning for cervical
      and cervicothoracic deformities. METHODS: Patients who underwent cervical
      osteotomies for cervical deformity were identified in a 10-year period from 2000
      to 2010. Demographics, surgery type, osteotomy type (Smith-Petersen Osteotomy
      [SPO], pedicle subtraction osteotomy [PSO], anterior-osteotomy [ATO]), operative
      details, and radiographs were collected for preoperative and ultimate
      postoperative time points. Cervical lordosis and basion plumb line were collected
      to assess angular and translational corrections. RESULTS: A total of 61 patients
      had surgery for cervical deformity in the study period. The mean angular
      correction generated through 1 SPO was 10.1 degrees  per level (range, 1.0
      degrees -24.9 degrees /level) and the mean translational correction was 1.8 cm
      (range, 0.5-4.0 cm/SPO). A PSO generated a mean angular correction of 34.5
      degrees  (range, 28.2 degrees - 80.0 degrees /level, maximum 1/case) per PSO and
      translational correction of 2.5 cm per PSO (range, 0.2-5.6 cm). An ATO generated
      a mean angular correction of 17.1 degrees  per osteotomy (range, 3.5 degrees 
      32.1 degrees /level) and translational correction of 1.0 cm per osteotomy (range,
      0.1-3.0 cm/level; total, 0.5-3 cm). Combined ATO and SPO with posterior cervical
      fusion generated a mean angular correction of 27.8 degrees  per osteotomy (range,
      3.7 degrees -66.7 degrees /level) and translational correction of 2.6 cm per
      osteotomy (range, 0.2-7.0 cm/level). CONCLUSION: Posteriorly based osteotomies
      provided better translational correction than ATOs. The angular correction
      achieved by 1 PSO was similar to ATO+SPOs. ATO+SPOs provided equal or better
      corrections than isolated PSOs, with equal length of stay and less estimated
      blood loss. LEVEL OF EVIDENCE: 4.

PMID- 25394320
TI  - A multiple testing method for hypotheses structured in a directed acyclic graph.
AB  - We present a novel multiple testing method for testing null hypotheses that are
      structured in a directed acyclic graph (DAG). The method is a top-down method
      that strongly controls the familywise error rate and can be seen as a
      generalization of Meinshausen's procedure for tree-structured hypotheses. Just as
      Meinshausen's procedure, our proposed method can be used to test for variable
      importance, only the corresponding variable clusters can be chosen more freely,
      because the method allows for multiple parent nodes and partially overlapping
      hypotheses. An important application of our method is in gene set analysis, in
      which one often wants to test multiple gene sets as well as individual genes for
      their association with a clinical outcome. By considering the genes and gene sets
      as nodes in a DAG, our method enables us to test both for significant gene sets
      as well as for significant individual genes within the same multiple testing
      procedure. The method will be illustrated by testing Gene Ontology terms for
      evidence of differential expression in a survival setting and is implemented in
      the R package cherry. 

PMID- 25394322
TI  - Communicating uncertainty--Ebola, public health, and the scientific process.

PMID- 25394321
TI  - Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy.
AB  - BACKGROUND: Idiopathic membranous nephropathy is an autoimmune disease. In
      approximately 70% of patients, it is associated with autoantibodies against the
      phospholipase A2 receptor 1 (PLA2R1). Antigenic targets in the remaining patients
      are unknown. METHODS: Using Western blotting, we screened serum samples from
      patients with idiopathic membranous nephropathy, patients with other glomerular
      diseases, and healthy controls for antibodies against human native glomerular
      proteins. We partially purified a putative new antigen, identified this protein
      by means of mass spectrometry of digested peptides, and validated the results by
      analysis of recombinant protein expression, immunoprecipitation, and
      immunohistochemical analysis. RESULTS: Serum samples from 6 of 44 patients in a
      European cohort and 9 of 110 patients in a Boston cohort with anti-PLA2R1
      negative idiopathic membranous nephropathy recognized a glomerular protein that
      was 250 kD in size. None of the serum samples from the 74 patients with
      idiopathic membranous nephropathy who were seropositive for anti-PLA2R1
      antibodies, from the 76 patients with other glomerular diseases, and from the 44
      healthy controls reacted against this antigen. Although this newly identified
      antigen is clearly different from PLA2R1, it shares some biochemical features,
      such as N-glycosylation, membranous location, and reactivity with serum only
      under nonreducing conditions. Mass spectrometry identified this antigen as
      thrombospondin type-1 domain-containing 7A (THSD7A). All reactive serum samples
      recognized recombinant THSD7A and immunoprecipitated THSD7A from glomerular
      lysates. Moreover, immunohistochemical analyses of biopsy samples from patients
      revealed localization of THSD7A to podocytes, and IgG eluted from one of these
      samples was specific for THSD7A. CONCLUSIONS: In our cohort, 15 of 154 patients
      with idiopathic membranous nephropathy had circulating autoantibodies to THSD7A
      but not to PLA2R1, a finding that suggests a distinct subgroup of patients with
      this condition. (Funded by the French National Center for Scientific Research and
      others.).

PMID- 25394323
TI  - Collyricloides massanae (Digenea, Collyriclidae): spermatozoon ultrastructure and
      phylogenetic importance.
AB  - The spermatological characteristics of Collyricloides massanae (Digenea:
      Collyriclidae), a parasite of Apodemus sylvaticus caught in France, were studied
      by means of transmission electron microscopy. The mature sperm of C. massanae
      presents two axonemes of different lengths with the 9 + "1" pattern of the
      Trepaxonemata, two bundles of parallel cortical microtubules, external
      ornamentation of the plasma membrane, spine-like bodies, one mitochondrion, a
      nucleus and granules of glycogen. An analysis of spermatological organisation
      emphasised some differences between the mature spermatozoon of C. massanae and
      those reported in the Gorgoderoidea species studied to date, specially belonging
      to the families Dicrocoeliidae, Paragonimidae and Troglotrematidae. The
      ultrastructural criteria described in C. massanae such as the morphology of both
      anterior and posterior spermatozoon extremities, the association "external
      ornamentation+cortical microtubules", the type 2 of external ornamentation and
      the spine-like bodies would allow us to bring closer the Collyriclidae to
      Microphalloidea. However, further ultrastructural and molecular studies are
      needed particularly in the unexplored taxa in order to fully resolve the
      phylogenetic position of the Collyriclidae.

PMID- 25394324
TI  - 1H MRS characterization of neurochemical profiles in orthotopic mouse models of
      human brain tumors.
AB  - Glioblastoma (GBM), the most common primary brain tumor, is resistant to
      currently available treatments. The development of mouse models of human GBM has
      provided a tool for studying mechanisms involved in tumor initiation and growth
      as well as a platform for preclinical investigation of new drugs. In this study
      we used (1) H MR spectroscopy to study the neurochemical profile of a human
      orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to
      evaluate differences in metabolite concentrations in the GBM HOT mice when
      compared with normal mouse brain in order to determine if MRS could reliably
      differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was
      used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels
      for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were
      reliably detected in all mouse spectra. The tumors had significantly lower
      concentrations of total creatine, GABA, glutamate, total N-acetylaspartate,
      aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm
      than did the brains of normal mice. The concentrations of glycine and lactate,
      however, were significantly higher in tumors than in normal brain.

PMID- 25394325
TI  - POCS-based reconstruction of multiplexed sensitivity encoded MRI (POCSMUSE): A
      general algorithm for reducing motion-related artifacts.
AB  - PURPOSE: A projection onto convex sets reconstruction of multiplexed sensitivity
      encoded MRI (POCSMUSE) is developed to reduce motion-related artifacts, including
      respiration artifacts in abdominal imaging and aliasing artifacts in interleaved
      diffusion-weighted imaging. THEORY: Images with reduced artifacts are
      reconstructed with an iterative projection onto convex sets (POCS) procedure that
      uses the coil sensitivity profile as a constraint. This method can be applied to
      data obtained with different pulse sequences and k-space trajectories. In
      addition, various constraints can be incorporated to stabilize the reconstruction
      of ill-conditioned matrices. METHODS: The POCSMUSE technique was applied to
      abdominal fast spin-echo imaging data, and its effectiveness in respiratory
      triggered scans was evaluated. The POCSMUSE method was also applied to reduce
      aliasing artifacts due to shot-to-shot phase variations in interleaved diffusion
      weighted imaging data corresponding to different k-space trajectories and matrix
      condition numbers. RESULTS: Experimental results show that the POCSMUSE technique
      can effectively reduce motion-related artifacts in data obtained with different
      pulse sequences, k-space trajectories and contrasts. CONCLUSION: POCSMUSE is a
      general post-processing algorithm for reduction of motion-related artifacts. It
      is compatible with different pulse sequences, and can also be used to further
      reduce residual artifacts in data produced by existing motion artifact reduction
      methods.

PMID- 25394326
TI  - A depressive endophenotype of poorer cognition among cognitively healthy
      community-dwelling adults: results from the Western Australia memory study.
AB  - OBJECTIVE: The objective was to evaluate in a cognitively normal population the
      utility of an endophenotype of the depression-cognition link previously shown to
      be related to cognitive functioning in mild cognitive impairment and Alzheimer's
      disease. METHODS: The data of 460 cognitively normal adults aged 32-92 years (M =
      63.5, standard deviation = 9.24) from the Western Australian Memory Study with
      the Cross-national comparisons of the Cambridge Cognitive Examination-revised
      (CAMCOG-R) scores and 30-item Geriatric Depression Scale (GDS) scores were
      analyzed to determine the relationship between the five-item depressive
      endophenotype (DepE) scale drawn from the GDS and level of performance on a
      measure of cognitive functioning. RESULTS: For the entire sample, there was a
      nonsignificant trend toward a negative relationship between DepE and CAMCOG-R
      scores. When analyzed for those 65 years and older, there was a significant
      negative relationship between the two measures (p = 0.001) with DepE scores
      significantly increasing the risk for performing more poorly on the CAMCOG-R
      (odds ratio = 1.53). Analysis of data for those 70 years and older showed that
      DepE was the only predictor significantly related to poorer CAMCOG-R performance
      (p = 0.001). For the 70 years and older group, DepE scores significantly
      increased the risk of poorer CAMCOG-R scores (odds ratio = 2.23). Analysis of the
      entire sample on the basis of ApoEepsilon4 carrier status revealed that DepE
      scores were significantly negatively related only to ApoEepsilon4 noncarrier
      regardless of age. CONCLUSIONS: Elevated DepE scores are associated with poor
      neuropsychological performance among cognitively normal older adults. Use of the
      DepE may allow for the identification of a subset of older adults where
      depression is a primary factor in cognitive decline and who may benefit from
      antidepressant therapies.

PMID- 25394327
TI  - Genomic organization of Hox and ParaHox clusters in the echinoderm, Acanthaster
      planci.
AB  - The organization of echinoderm Hox clusters is of interest due to the role that
      Hox genes play in deuterostome development and body plan organization, and the
      unique gene order of the Hox complex in the sea urchin Strongylocentrotus
      purpuratus, which has been linked to the unique development of the axial region.
      Here, it has been reported that the Hox and ParaHox clusters of Acanthaster
      planci, a corallivorous starfish found in the Pacific and Indian oceans,
      generally resembles the chordate and hemichordate clusters. The A. planci Hox
      cluster shared with sea urchins the loss of one of the medial Hox genes, even
      skipped (Evx) at the anterior of the cluster, as well as organization of the
      posterior Hox genes.

PMID- 25394328
TI  - Enzymatic halogenation of tryptophan on a gram scale.
AB  - Halogenated arenes are important building blocks in medicinal and agrochemistry.
      Chemical electrophilic aromatic halogenation requires molecular halogen, whereas
      FAD-dependent halogenases form halogenated arenes with high regioselectivity
      while only halide salts and O2 are required. This reaction proceeds at room
      temperature in aqueous media. However, enzymatic halogenation is considered
      inefficient, mainly because halogenases are not stable. Thus, the preparative
      application remained elusive. We were able to show that the long-term stability
      and, hence, the preparative efficiency of the tryptophan-7-halogenase RebH can be
      significantly improved by immobilization together with the other enzymes required
      for cofactor regeneration. We established a facile scalable method suitable for
      the halogenation of tryptophan and its derivatives on a gram scale using a solid,
      multifunctional, and recyclable biocatalyst; this immobilization strategy might
      also be applicable for other FAD-dependent halogenases. 

PMID- 25394329
TI  - The evolution of eukaryotic cells from the perspective of peroxisomes:
      phylogenetic analyses of peroxisomal beta-oxidation enzymes support mitochondria
      first models of eukaryotic cell evolution.
AB  - Beta-oxidation of fatty acids and detoxification of reactive oxygen species are
      generally accepted as being fundamental functions of peroxisomes. Additionally,
      these pathways might have been the driving force favoring the selection of this
      compartment during eukaryotic evolution. Here we performed phylogenetic analyses
      of enzymes involved in beta-oxidation of fatty acids in Bacteria, Eukaryota, and
      Archaea. These imply an alpha-proteobacterial origin for three out of four
      enzymes. By integrating the enzymes' history into the contrasting models on the
      origin of eukaryotic cells, we conclude that peroxisomes most likely evolved non
      symbiotically and subsequent to the acquisition of mitochondria in an archaeal
      host cell. 

PMID- 25394330
TI  - Highly ordered nanoporous carbon films with tunable pore diameters and their
      excellent sensing properties.
AB  - Ordered porous carbon films with tunable pore diameters, immobilized with glucose
      oxidase (GOD) have been fabricated and employed for the construction of a
      biosensor for glucose molecules. The as-prepared porous films have large specific
      surface areas and highly ordered porous structure with uniform pore sizes, which
      are critical for the immobilization of large amounts of GOD and support the
      promotion of heterogeneous electron transfer. The developed biosensors give
      enough room for the encapsulation of a high amount of GOD molecules and show
      excellent biosensing performance with a linear response to glucose concentration
      ranging from 0.5 to 9 mM and a detection limit of 1.5 MUM. It is also
      demonstrated that the sensitivity of the biosensor can be easily tuned by
      modulating the pore size of carbon film as it dictates the amount of
      immobilization of GOD in the porous channels. The fabricated carbon-film-based
      biosensor has a good stability and a high reproducibility, which opens the
      gateway for the commercialization of this excellent technology. 

PMID- 25394331
TI  - The fluence effects of low-level laser therapy on inflammation, fibroblast-like
      synoviocytes, and synovial apoptosis in rats with adjuvant-induced arthritis.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser
      therapy (LLLT) operating at low and high fluences on joint inflammation,
      fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant
      induced arthritis. BACKGROUND DATA: Rheumatoid arthritis (RA) is characterized by
      pronounced inflammation and FLS proliferation within affected joints. Certain
      data indicate that LLLT is effective in patients with inflammation caused by RA;
      however, the fluence effects of LLLT on synovium are unclear. METHODS:
      Monoarthritis was induced in adult male Sprague-Dawley rats (250-300 g) via
      intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal
      joint. Animals were irradiated 72 h after CFA administration with a 780 nm GaAlAs
      laser at 4.5 J/cm2 (30 mW, 30 sec/spot) and 72 J/cm2 (80 mW, 180 sec/spot) daily
      for 10 days. After LLLT, the animals were euthanized and their arthritic ankles
      were collected for histopathological analysis, immunoassays of tumor necrosis
      factor (TNF)-alpha, matrix metallopeptidase (MMP)3 and 5B5, and terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: LLLT
      at a fluence of 4.5 J/cm2 significantly reduced infiltration of inflammatory
      cells and expressions of TNF-alpha-, MMP3- and 5B5-like immunoreactivities, as
      well as resulting in more TUNEL-positive apoptotic cells in the synovium. No
      significant changes were observed in these biochemicals and inflammation in
      arthritic animals treated with 72 J/cm2. CONCLUSIONS: LLLT with low fluence is
      highly effective in reducing inflammation to sites of injury by decreasing the
      numbers of FLS, inflammatory cells, and mediators in the CFA-induced arthritic
      model. These data will be of value in designing clinical trials of LLLT for RA.

PMID- 25394332
TI  - Connecting carbon and nitrogen storage in rural wetland soil to groundwater
      abstraction for urban water supply.
AB  - We investigated whether groundwater abstraction for urban water supply diminishes
      the storage of carbon (C), nitrogen (N), and organic matter in the soil of rural
      wetlands. Wetland soil organic matter (SOM) benefits air and water quality by
      sequestering large masses of C and N. Yet, the accumulation of wetland SOM
      depends on soil inundation, so we hypothesized that groundwater abstraction would
      diminish stocks of SOM, C, and N in wetland soils. Predictions of this hypothesis
      were tested in two types of subtropical, depressional-basin wetland: forested
      swamps and herbaceous-vegetation marshes. In west-central Florida, >650 ML
      groundwater day(-1) are abstracted for use primarily in the Tampa Bay metropolis.
      At higher abstraction volumes, water tables were lower and wetlands had shorter
      hydroperiods (less time inundated). In turn, wetlands with shorter hydroperiods
      had 50-60% less SOM, C, and N per kg soil. In swamps, SOM loss caused soil bulk
      density to double, so areal soil C and N storage per m(2) through 30.5 cm depth
      was diminished by 25-30% in short-hydroperiod swamps. In herbaceous-vegetation
      marshes, short hydroperiods caused a sharper decline in N than in C. Soil organic
      matter, C, and N pools were not correlated with soil texture or with wetland
      draining-reflooding frequency. Many years of shortened hydroperiod were probably
      required to diminish soil organic matter, C, and N pools by the magnitudes we
      observed. This diminution might have occurred decades ago, but could be
      maintained contemporarily by the failure each year of chronically drained soils
      to retain new organic matter inputs. In sum, our study attributes the contraction
      of hydroperiod and loss of soil organic matter, C, and N from rural wetlands to
      groundwater abstraction performed largely for urban water supply, revealing
      teleconnections between rural ecosystem change and urban resource demand. 

PMID- 25394333
TI  - From ergolines to indoles: improved inhibitors of the human H3 receptor for the
      treatment of narcolepsy.
AB  - Ergolines were recently identified as a novel class of H3 receptor (H3R) inverse
      agonists. Although their optimization led to drug candidates with encouraging
      properties for the treatment of narcolepsy, brain penetration remained low. To
      overcome this issue, ergoline 1 ((6aR,9R,10aR)-4-(2-(dimethylamino)ethyl)-N
      phenyl-9-(pyrrolidine-1-carbonyl)-6,6a,8,9,10,10a-hexahydroindolo[4,3
      fg]quinoline-7(4H)-carboxamide)) was transformed into a series of indole
      derivatives with high H3R affinity. These new molecules were profiled by
      simultaneous determination of their brain receptor occupancy (RO) levels and
      pharmacodynamic (PD) effects in mice. These efforts culminated in the discovery
      of 15 m ((R)-1-isopropyl-5-(1-(2-(2-methylpyrrolidin-1-yl)ethyl)-1H-indol-4
      yl)pyridin-2(1H)-one), which has an ideal profile showing a strong correlation of
      PD effects with RO, and no measurable safety liabilities. Its desirably short
      duration of action was confirmed by electroencephalography (EEG) measurements in
      rats.

PMID- 25394334
TI  - Superior ion-conducting hybrid solid electrolyte for all-solid-state batteries.
AB  - Herein, we developed a high-performance lithium ion conducting hybrid solid
      electrolyte, consisted of LiTFSI salt, Py14 TFSI ionic liquid, and TiO2
      nanoparticles. The hybrid solid electrolyte prepared by a facile method had high
      room temperature ionic conductivity, excellent thermal stability and low
      interface resistance with good contact. In addition, the lithium transference
      number was highly increased by the scavenger effect of TiO2 nanoparticles. With
      the hybrid solid electrolyte, the pouch-type solid-state battery exhibited high
      initial discharge capacity of 150 mA h g(-1) at room temperature, and even at 1
      C, the reversible capacity was as high as 106 mA h g(-1) . 

PMID- 25394335
TI  - Increasing parental age at childbirth is associated with greater insulin
      sensitivity and more favorable metabolic profile in overweight adult male
      offspring.
AB  - OBJECTIVE: To assess the effect of parental age at childbirth on insulin
      sensitivity and other metabolic outcomes in overweight middle-aged males.
      METHODS: We studied 73 men aged 46.0+/-5.4 years, who were overweight (body mass
      index, BMI 25-30 kg/m(2) ) but otherwise healthy. Insulin sensitivity was
      assessed by the Matsuda method from an oral glucose tolerance test. Other
      assessments included dual-energy X-ray absorptiometry-derived body composition,
      lipid profile, 24-hour ambulatory blood pressure, and carotid intima-media
      thickness. Maternal and paternal ages were highly correlated (r = 0.71; P <
      0.0001), and the main parameter of interest in this study was the mean parental
      age at childbirth (MPAC), calculated as the average of maternal and paternal
      ages. RESULTS: Increasing MPAC was associated with a continuous increase in
      insulin sensitivity (beta = 0.193; P = 0.008), as well as reductions in insulin
      resistance (HOMA-IR; beta = -0.064; P = 0.011), fasting insulin (beta = -0.221; P
      = 0.018) and fasting glucose (beta = -0.030; P = 0.033) concentrations.
      Increasing MPAC was also associated with reductions in night time systolic (beta
      = -0.500; P = 0.020) and diastolic (beta = -0.325; P = 0.047) blood pressure, as
      well as with improved (greater) nocturnal diastolic blood pressure dipping (beta
      = 0.413; P = 0.046). Subgroup analyses on participants of European descent (n =
      64) showed that increasing MPAC was associated with reduced carotid intima-media
      thickness (beta = -0.008; P = 0.018) and lower low-density lipoprotein
      cholesterol concentrations (beta = -0.042; P = 0.028). CONCLUSIONS: Increasing
      parental age at childbirth was associated with a more favorable metabolic
      phenotype in overweight middle-aged males. However, it is unknown whether the
      effect was maternal, paternal, or both. Future studies on the effects of parental
      age at childbirth on the metabolism of males and females across the BMI range are
      required.

PMID- 25394336
TI  - Interprofessionalism: Educating to meet patient needs.
AB  - Interprofessional teams in health care are showing promise in achieving the
      triple aim-providing better care for the individual patient, reducing costs, and
      improving population health. To complement current changes in health care
      delivery in the United States, there is a growing consensus among health
      professions educators that students should be trained in interprofessional models
      prior to entering clinical practice. Current interprofessional education (IPE)
      efforts in anatomy education are producing positive results in enhancing
      professional respect, collaboration, and teamwork among health professions
      students. In spite of existing structural and cultural barriers to IPE, health
      professions educators must continue to lead and grow IPE efforts as a critical
      component to improving the health of our nation.

PMID- 25394337
TI  - Good-Turing frequency estimation in a finite population.
AB  - Good-Turing frequency estimation (Good, ) is a simple, effective method for
      predicting detection probabilities of objects of both observed and unobserved
      classes based on observed frequencies of classes in a sample. The method has been
      used widely in several disciplines, such as information retrieval, computational
      linguistics, text recognition, and ecological diversity estimation. Nevertheless,
      existing studies assume sampling with replacement or sampling from an infinite
      population, which might be inappropriate for many practical applications. In
      light of this limitation, this article presents a modification of the Good-Turing
      estimation method to account for finite population sampling. We provide three
      practical extensions of the modified method, and we examine performance of the
      modified method and its extensions in simulation experiments. 

PMID- 25394338
TI  - Analysis of left ventricular function of the mouse heart during experimentally
      induced hyperthyroidism and recovery.
AB  - Many of the clinical manifestations of hyperthyroidism are due to the ability of
      thyroid hormones to alter myocardial contractility and cardiovascular
      hemodynamics, leading to cardiovascular impairment. In contrast, recent studies
      highlight also the potential beneficial effects of thyroid hormone administration
      for clinical or preclinical treatment of different diseases such as
      atherosclerosis, obesity and diabetes or as a new therapeutic approach in
      demyelinating disorders. In these contexts and in the view of developing thyroid
      hormone-based therapeutic strategies, it is, however, important to analyze
      undesirable secondary effects on the heart. Animal models of experimentally
      induced hyperthyroidism therefore represent important tools for investigating and
      monitoring changes of cardiac function. In our present study we use high-field
      cardiac MRI to monitor and follow-up longitudinally the effects of prolonged
      thyroid hormone (triiodothyronine) administration focusing on murine left
      ventricular function. Using a 9.4 T small horizontal bore animal scanner,
      cinematographic MRI was used to analyze changes in ejection fraction, wall
      thickening, systolic index and fractional shortening. Cardiac MRI investigations
      were performed after sustained cycles of triiodothyronine administration and
      treatment arrest in adolescent (8 week old) and adult (24 week old) female
      C57Bl/6 N mice. Triiodothyronine supplementation of 3 weeks led to an impairment
      of cardiac performance with a decline in ejection fraction, wall thickening,
      systolic index and fractional shortening in both age groups but with a higher
      extent in the group of adolescent mice. However, after a hormonal treatment
      cessation of 3 weeks, only young mice are able to partly restore cardiac
      performance in contrast to adult mice lacking this recovery potential and
      therefore indicating a presence of chronically developed heart pathology.

PMID- 25394340
TI  - [Dental screening in patients with rheumatic disease].
AB  - Dental screening features of patients having rheumatic diseases are reviewed
      concerning such factors as examination and oral hygiene sessions frequency,
      specific rheumatic disease (rheumatoid arthritis, system lupus erythematosus and
      systemic sclerosis), oral and dental disorders (periodontal disease, dental
      caries, salivary glands disorders).

PMID- 25394339
TI  - Structure based computational assessment of channel properties of assembled ORF
      8a from SARS-CoV.
AB  - ORF 8a is a short 39 amino acid bitopic membrane protein encoded by severe acute
      respiratory syndrome causing corona virus (SARS-CoV). It has been identified to
      increase permeability of the lipid membrane for cations. Permeability is
      suggested to occur due to the assembly of helical bundles. Computational models
      of a pentameric assembly of 8a peptides are generated using the first 22 amino
      acids, which include the transmembrane domain. Low energy structures reveal a
      hydrophilic pore mantled by residues Thr-8, and -18, Ser-11, Cys-13, and Arg-22.
      Potential of mean force (PMF) profiles for mono (Na(+) , K(+) , Cl(-) ) and
      divalent (Ca(2+) ) ions along the pore are calculated. The data support
      experimental findings of a weak cation selectivity of the channel. Calculations
      on 8a are compared to data derived for a pentameric bundle consisting of the M2
      helices of the bacterial pentameric ligand gated ion channel GLIC (3EHZ). PMF
      curves of both, bundles 8a and M2, show sigmoidal shaped profiles. In comparison
      to the data for the M2-GLIC model, data of the 8a bundle show lower amplitude of
      the PMF values between maximum and minimum and less discrimination amongst ions.

PMID- 25394341
TI  - [In memorial of outstanding historian of medicine and dentistry G.N. Troyanskiy
      (on the occasion of 90th anniversary)].

PMID- 25394342
TI  - [Prof. V.N. Kopeykin (on the occasion of 85th anniversary)].

PMID- 25394343
TI  - [The creative career of professor Iu. I. Krasil'nikov, the honoured physician of
      the Russian federation].

PMID- 25394344
TI  - [Genotyping on Yersinia pestis isolated from Yunnan province by clustered
      regularly-interspaced-short palindromic-repeats].

PMID- 25394345
TI  - [Study on the bactericidal antibody of healthy population against the prevalent
      Neisseria meningitides strain of serogroup C in Shanghai].

PMID- 25394346
TI  - Anonymity.  HIV-positive man's request to proceed anonymously denied.

PMID- 25394348
TI  - SSI.  Woman with HIV capable of performing work, court says.

PMID- 25394347
TI  - Woman who acquired HIV from transplant granted new trial.

PMID- 25394349
TI  - Warren Keith Sinclair (1924 to 2014).

PMID- 25394350
TI  - Sexual and reproductive health and rights post 2015--challenges and
      opportunities.

PMID- 25394351
TI  - Robuvit(r) (Quercus robur extract) supplementation in subjects with chronic
      fatigue syndrome and increased oxidative stress. A pilot registry study.
AB  - AIM: The aim of this registry study was to evaluate the effects of
      supplementation with Robuvit(r) (French Quercus robur extract) capsules in
      subjects with Chronic Fatigue Syndrome (CFS) associated with an increased
      oxidative stress. Robuvit is a wood extract from Quercus robur (Horphag Research)
      used to improve liver dysfunction and chronic fatigue. After excluding any
      disease, subjects observed a defined management plan to improve CFS.
      Signs/symptoms had been present for more than 6 months in association with an
      increase in oxidative stress (measured as plasma free radicals). Blood tests were
      within normal values. METHODS: The registry study included 38 CFS subjects and 42
      comparable controls. There were no dropouts in the 4 weeks of follow-up; the
      subjects were evaluated for a further period of 6 months. The management plan
      included: improved/increased sleep; reduction/abolition in smoking and alcohol or
      any other agent that may have affected them; control of diet, increase in dietary
      proteins; good hydration; rest (1/2-1 h/day) and exercise (at least 30 min/day);
      planned relaxation time; increased time in open spaces. In the Robuvit(r)
      supplementation group 300 mg/day of Robuvit(r) was used. RESULTS: Symptoms
      improved in both groups with a significantly more important improvement in the
      supplement group (P<0.05). The single items in the Multidimensional Assessment of
      Fatigue (MAF) questionnaire were statistically better improved (P<0.05) in the
      supplement group. A parallel improvement in oxidative stress was observed in the
      supplemented subjects. In the follow up, at 6 months no organic disease was
      discovered or disease markers found. CONCLUSION: This preliminary registry
      indicates that supplementation with Robuvit(r) improves CFS in otherwise healthy
      subjects with no presence of clinical disease or risk conditions. The effects of
      Robuvit(r) in CFS may be partially mediated by a clear reduction of plasma free
      radicals and oxidative stress.

PMID- 25394354
TI  - [Patient safety in education and training of healthcare professionals in
      Germany].
AB  - In order to improve patient safety, healthcare professionals who care for
      patients directly or indirectly are required to possess specific knowledge and
      skills. Patient safety education is not or only poorly represented in education
      and examination regulations of healthcare professionals in Germany; therefore, it
      is only practiced rarely and on a voluntary basis. Meanwhile, several training
      curricula and concepts have been developed in the past 10 years internationally
      and recently in Germany, too. Based on these concepts the German Coalition for
      Patient Safety developed a catalogue of core competencies required for safety in
      patient care. This catalogue will serve as an important orientation when patient
      safety is to be implemented as a subject of professional education in Germany in
      the future. Moreover, teaching staff has to be trained and educational and
      training activities have to be evaluated. Patient safety education and training
      for (undergraduate) healthcare professional will require capital investment. 

PMID- 25394353
TI  - Splicing mutation analysis reveals previously unrecognized pathways in lymph node
      invasive breast cancer.
AB  - Somatic mutations reported in large-scale breast cancer (BC) sequencing studies
      primarily consist of protein coding mutations. mRNA splicing mutation analyses
      have been limited in scope, despite their prevalence in Mendelian genetic
      disorders. We predicted splicing mutations in 442 BC tumour and matched normal
      exomes from The Cancer Genome Atlas Consortium (TCGA). These splicing defects
      were validated by abnormal expression changes in these tumours. Of the 5,206
      putative mutations identified, exon skipping, leaky or cryptic splicing was
      confirmed for 988 variants. Pathway enrichment analysis of the mutated genes
      revealed mutations in 9 NCAM1-related pathways, which were significantly
      increased in samples with evidence of lymph node metastasis, but not in lymph
      node-negative tumours. We suggest that comprehensive reporting of DNA sequencing
      data should include non-trivial splicing analyses to avoid missing clinically
      significant deleterious splicing mutations, which may reveal novel mutated
      pathways present in genetic disorders. 

PMID- 25394355
TI  - [Safety of medical devices].

PMID- 25394356
TI  - A duplication of the whole KIAA2022 gene validates the gene role in the
      pathogenesis of intellectual disability and autism.

PMID- 25394357
TI  - Deciphering ligands' interaction with Cu and Cu2O nanocrystal surfaces by NMR
      solution tools.
AB  - The hydrogenolysis of [Cu2{(iPrN)2(CCH3)}2] in the presence of hexadecylamine
      (HDA) or tetradecylphosphonic acid (TDPA) in toluene leads to 6-9 nm copper
      nanocrystals. Solution NMR spectroscopy has been used to describe the
      nanoparticle surface chemistry during the dynamic phenomenon of air oxidation.
      The ligands are organized as multilayered shells around the nanoparticles. The
      shell of ligands is controlled by both their intermolecular interactions and
      their bonding strength on the nanocrystals. Under ambient atmosphere, the
      oxidation rate of colloidal copper nanocrystals closely relies on the chemical
      nature of the employed ligands (base or acid). Primary amine molecules behave as
      soft ligands for Cu atoms, but are even more strongly coordinated on surface
      Cu(I) sites, thus allowing a very efficient corrosion protection of the copper
      core. On the contrary, the TDPA ligands lead to a rapid oxidation rate of Cu
      nanoparticles and eventually to the re-dissolution of Cu(II) species at the
      expense of the nanocrystals.

PMID- 25394358
TI  - Generalized approach to the microstructure direction in metal oxide ceramics via
      polymerization-induced phase separation.
AB  - When three-dimensionally ordered macroporous (3DOM) materials are synthesized in
      polymeric colloidal crystal templates using a Pechini-type approach,
      polymerization-induced phase separation (PIPS) can occur. Depending on the
      reaction conditions, the porous products have a variety of morphologies,
      including an extended inverse opal structure, bicontinuous networks of 3DOM
      materials interrupted by extended voids, uniform 3DOM microspheres, sheet
      structures of templated macroporous oxides, and hollow particles obtained by
      structural disassembly. In this study, the mechanism underpinning morphology
      control of 3DOM metal oxides through PIPS is elucidated for Ce(0.5)Mg(0.5)O(1.5)
      and CeO(2) systems. The mechanistic information is then applied to synthesize
      target morphologies for Mn(3)O(4) and Fe(2)O(3)/Fe(3)O(4) systems, demonstrating
      the more general nature of the synthetic approach for aqueous metal precursors
      that can be complexed with citric acid. The effects of reactant balance,
      complexation behavior, processing temperature, and template sphere size are
      related directly to the microstructures obtained. The predominant controlling
      factor of microstructural evolution in PIPS Pechini precursors is found to be the
      degree of polymerization of the polyester, which can be controlled through
      tailoring the reagent imbalance. 3DOM microspheres produced by the method are
      between 0.5 and 3 MUm in size, with polydispersities below 25%.

PMID- 25394359
TI  - Emerging role of microRNAs in modulating endothelin-1 expression in gastric
      cancer.
AB  - Endothelin-1 (ET-1) is a small 21-amino acid peptide that is known to exert
      diverse biological effects on a wide variety of tissues and cell types through
      its own receptors. The ET-1-ETRA axis is frequently dysfunctional in numerous
      types of carcinomas, and contributes to the promotion of cell growth and
      migration. microRNAs (miRNAs) are small non-coding RNAs that play a critical role
      in carcinogenesis through mRNA degradation or the translational inhibition of
      cancer-associated protein-coding genes. However, the role of ET-1 and the
      relationship between ET-1 and miRNAs in gastric cancer remain unknown. Results of
      the analysis of the database of The Cancer Genome Atlas (TCGA) revealed that ET-1
      is significantly overexpressed in gastric cancer cells when compared with its
      expression in adjacent normal cells. Exogenous ET-1 significantly enhanced
      gastric cancer cell proliferation, implying that ET-1 plays an oncogenic role in
      gastric cancer carcinogenesis. Using a luciferase reporter assay we showed that
      18 miRNA candidates had a significant silencing effect on ET-1 expression by up
      to 20% in HEK293T cells. Among them, 5 miRNAs (miR-1, miR-101, miR-125A, miR-144
      and let-7c) were shown to be involved in ET-1 silencing through post
      transcriptional modulation in gastric cancer. Our data also revealed that DNA
      hypermethylation contributes to the silenced miR-1 expression in gastric cancer
      cells. The ectopic expression of miR-1 significantly inhibited AGS cell
      proliferation by suppressing ET-1 expression. Overall, our study revealed that ET
      1 overexpression may be due to DNA hypermethylation resulting in the silencing of
      miR-1 expression in gastric cancer cells. In addition, we identified several
      miRNAs as potential modulators for ET-1 in gastric cancer, which may be used as
      targets for gastric cancer therapy.

PMID- 25394360
TI  - Rapid measurement of molecular transport and interaction inside living cells
      using single plane illumination.
AB  - The ability to measure biomolecular dynamics within cells and tissues is very
      important to understand fundamental physiological processes including cell
      adhesion, signalling, movement, division or metabolism. Usually, such information
      is obtained using particle tracking methods or single point fluctuation
      spectroscopy. We show that image mean square displacement analysis, applied to
      single plane illumination microscopy data, is a faster and more efficient way of
      unravelling rapid, three-dimensional molecular transport and interaction within
      living cells. From a stack of camera images recorded in seconds, the type of
      dynamics such as free diffusion, flow or binding can be identified and quantified
      without being limited by current camera frame rates. Also, light exposure levels
      are very low and the image mean square displacement method does not require
      calibration of the microscope point spread function. To demonstrate the
      advantages of our approach, we quantified the dynamics of several different
      proteins in the cyto- and nucleoplasm of living cells. For example, from a single
      measurement, we were able to determine the diffusion coefficient of free clathrin
      molecules as well as the transport velocity of clathrin-coated vesicles involved
      in endocytosis. Used in conjunction with dual view detection, we further show how
      protein-protein interactions can be quantified. 

PMID- 25394361
TI  - Popularizing dissent: A civil society perspective.
AB  - This article theorizes civil society groups' attempts to popularize opposition to
      genetic modification in New Zealand as deliberative interventions that seek to
      open up public participation in science-society governance. In this case, the
      popularization strategies were designed to intensify concerns about social
      justice and democratic incursions, mobilize dissent and offer meaningful
      mechanisms for navigating and participating in public protest. Such civic
      popularization efforts, we argue, are more likely to succeed when popularity and
      politicization strategies are judiciously integrated to escalate controversy, re
      negotiate power relations and provoke agency and action. 

PMID- 25394362
TI  - Author's reply to Agius and Verdolini.

PMID- 25394363
TI  - Decoupling of evolutionary changes in transcription factor binding and gene
      expression in mammals.
AB  - To understand the evolutionary dynamics between transcription factor (TF) binding
      and gene expression in mammals, we compared transcriptional output and the
      binding intensities for three tissue-specific TFs in livers from four closely
      related mouse species. For each transcription factor, TF-dependent genes and the
      TF binding sites most likely to influence mRNA expression were identified by
      comparing mRNA expression levels between wild-type and TF knockout mice.
      Independent evolution was observed genome-wide between the rate of change in TF
      binding and the rate of change in mRNA expression across taxa, with the exception
      of a small number of TF-dependent genes. We also found that binding intensities
      are preferentially conserved near genes whose expression is dependent on the TF,
      and the conservation is shared among binding peaks in close proximity to each
      other near the TSS. Expression of TF-dependent genes typically showed an
      increased sensitivity to changes in binding levels as measured by mRNA abundance.
      Taken together, these results highlight a significant tolerance to evolutionary
      changes in TF binding intensity in mammalian transcriptional networks and suggest
      that some TF-dependent genes may be largely regulated by a single TF across
      evolution. 

PMID- 25394364
TI  - Gas Chromatographic Method for the Analysis of Organic Acids in the Bio-Catalytic
      Conversion Process.
AB  - An analytical method for the quantification of acrylic acid (AA), 1,3-propanediol
      (1,3-PD) and 3-hydroxypropionic acid (3-HP) in the bio-catalytic conversion
      process has been developed by gas chromatography. A simple liquid-liquid
      extraction (LLE) procedure was used in the sample preparation. Organic acid
      additives such as trifluoroacetic acid were used to improve the extraction
      efficiency in the LLE procedure. Under optimum analysis conditions, all analytes
      were satisfactorily separated with no interference. In standard calibration, all
      correlation coefficients (r(2)) were better than or equal to 0.994. In culture
      media, the intra-batch precision (% relative standard deviation) and recovery (%)
      as the average value of the quality control samples were 2.3 and 102.4%,
      respectively. In addition, the inter-batch precision and recovery as the average
      value of the quality control samples were 5.0 and 104.0%, respectively. In
      phosphate buffer, the intra-batch precision and recovery as the average value of
      the quality control samples were 2.7 and 101.6%, respectively. In addition, the
      inter-batch precision and recovery as the average value of the quality control
      samples were 2.9 and 101.7%, respectively. The limit of detection (S/N ratio: 3)
      and limit of quantification (S/N ratio: 10) were 1.0 and 3.5 ug/mL, 3.0 and 10.0
      ug/mL, and 9.0 and 30.0 ug/mL, respectively, for AA, 1,3-PD and 3-HP.
      Consequently, this method was demonstrated to be acceptable for the quantitative
      analysis of AA, 1,3-PD and 3-HP in culture media and phosphate buffer. 

PMID- 25394365
TI  - Anti-endotoxic activity and structural basis for human MD-2.TLR4 antagonism of
      tetraacylated lipid A mimetics based on betaGlcN(1<->1)alphaGlcN scaffold.
AB  - Interfering with LPS binding by the co-receptor protein myeloid differentiation
      factor 2 (MD-2) represents a useful approach for down-regulation of MD-2.TLR4
      mediated innate immune signaling, which is implicated in the pathogenesis of a
      variety of human diseases, including sepsis syndrome. The antagonistic activity
      of a series of novel synthetic tetraacylated bis-phosphorylated glycolipids based
      on the betaGlcN(1<->1)alphaGlcN scaffold was assessed in human monocytic
      macrophage-like cell line THP-1, dendritic cells and human epithelial cells. Two
      compounds were shown to inhibit efficiently the LPS-induced inflammatory
      signaling by down-regulation of the expression of TNF-alpha, IL-6, IL-8, IL-10
      and IL-12 to background levels. The binding of the tetraacylated by (R)-3-hydroxy
      fatty acids (2 * C12, 2 * C14), 4,4'-bisphosphorylated betaGlcN(1<->1)alphaGlcN
      based lipid A mimetic DA193 to human MD-2 was calculated to be 20-fold stronger
      than that of Escherichia coli lipid A. Potent antagonistic activity was related
      to a specific molecular shape induced by the beta,alpha(1<->1)-diglucosamine
      backbone. 'Co-planar' relative arrangement of the GlcN rings was inflicted by the
      double exo-anomeric conformation around both glycosidic torsions in the rigid
      beta,alpha(1<->1) linkage, which was ascertained using NOESY NMR experiments and
      confirmed by molecular dynamics simulation. In contrast to the native lipid A
      ligands, the binding affinity of betaGlcN(1<->1)alphaGlcN-based lipid A mimetics
      to human MD-2 was independent on the orientation of the diglucosamine backbone of
      the synthetic antagonist within the binding pocket of hMD-2 (rotation by 180
      degrees ) allowing for two equally efficient binding modes as shown by molecular
      dynamics simulation. 

PMID- 25394366
TI  - Real-time simultaneous and proportional myoelectric control using intramuscular
      EMG.
AB  - OBJECTIVE: Myoelectric prostheses use electromyographic (EMG) signals to control
      movement of prosthetic joints. Clinically available myoelectric control
      strategies do not allow simultaneous movement of multiple degrees of freedom
      (DOFs); however, the use of implantable devices that record intramuscular EMG
      signals could overcome this constraint. The objective of this study was to
      evaluate the real-time simultaneous control of three DOFs (wrist rotation, wrist
      flexion/extension, and hand open/close) using intramuscular EMG. APPROACH: We
      evaluated task performance of five able-bodied subjects in a virtual environment
      using two control strategies with fine-wire EMG: (i) parallel dual-site
      differential control, which enabled simultaneous control of three DOFs and (ii)
      pattern recognition control, which required sequential control of DOFs. MAIN
      RESULTS: Over the course of the experiment, subjects using parallel dual-site
      control demonstrated increased use of simultaneous control and improved
      performance in a Fitts' Law test. By the end of the experiment, performance using
      parallel dual-site control was significantly better (up to a 25% increase in
      throughput) than when using sequential pattern recognition control for tasks
      requiring multiple DOFs. The learning trends with parallel dual-site control
      suggested that further improvements in performance metrics were possible.
      Subjects occasionally experienced difficulty in performing isolated single-DOF
      movements with parallel dual-site control but were able to accomplish related
      Fitts' Law tasks with high levels of path efficiency. SIGNIFICANCE: These results
      suggest that intramuscular EMG, used in a parallel dual-site configuration, can
      provide simultaneous control of a multi-DOF prosthetic wrist and hand and may
      outperform current methods that enforce sequential control.

PMID- 25394367
TI  - Reversing effect and mechanism of soluble resistance-related calcium-binding
      protein on multidrug resistance in human lung cancer A549/DDP cells.
AB  - Lung cancer is the primary malignancy of the lung and is the leading cause of
      cancer-associated mortality in China. Multidrug resistance (MDR) is an essential
      aspect of lung cancer treatment failure and a popular topic of investigation in
      tumor studies. Previous studies have demonstrated that soluble resistance-related
      calcium-binding protein (Sorcin) is involved in the MDR of various types of human
      tumor, and that silencing Sorcin was able to reverse the MDR of several types of
      cultured human cancer cells. However, the effect and potential mechanism
      underlying the ability of Sorcin to reverse MDR in human lung cancer remains to
      be fully elucidated. The present study examined the role of Sorcin in the
      reversal of MDR in human lung cancer A549/DDP cells. The effects included
      increased drug sensitivity to cisplatin, apoptotic rate, cell cycle arrest in the
      G2/M phase and intracellular accumulation of rhodamine-123, and decreased
      expression of multidrug resistance gene 1, lung resistance protein, multidrug
      resistance-associated protein, glutathione S-transferase pi, ATP-binding cassette
      transporter A2 (ABCA2), ABCA5, B-cell lymphoma 2 and P-glycoprotein, and the
      depletion of glutathione in Sorcin-silenced A549/DDP cells. The present study
      also revealed that there was a downregulation of p-Akt and phosphorylated
      extracellular signal-regulated kinase (p-ERK), and a decreased transcriptional
      activation of nuclear factor kappaB, signal transducer and activator of
      transcription (STAT)3, STAT5 and nuclear factor of activated T-cells following
      silencing of Sorcin. The results indicated that Sorcin may be used as a potential
      therapeutic target for MDR through inhibiting the Akt and ERK pathways in human
      lung cancer.

PMID- 25394368
TI  - Selective efficacy of zoledronic acid on metastasis in a patient-derived
      orthotopic xenograph (PDOX) nude-mouse model of human pancreatic cancer.
AB  - BACKGROUND AND OBJECTIVES: Patient-derived orthotopic xenograft (PDOX) nude-mouse
      models replicate the behavior of clinical cancer, including metastasis. The
      objective of the study was to determine the efficacy of zoledronic acid (ZA) on
      metastasis of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of
      pancreatic cancer. METHODS: In the present study, we examined the efficacy of ZA
      on pancreatic cancer growth and metastasis in a PDOX nude-mouse model. RESULTS:
      ZA monotherapy did not significantly suppress primary tumor growth. However, the
      primary tumor weight of gemcitabine (GEM) and combination GEM + ZA-treated mice
      was significantly decreased compared to the control group (GEM: P = 0.003; GEM +
      ZA: P = 0.002). The primary tumor weight of GEM + ZA-treated mice was
      significantly decreased compared to GEM-treated mice (P = 0.016). The metastasis
      weight decreased in ZA- or GEM-treated mice compared to the control group (ZA: P
      = 0.009; GEM: P = 0.007. No metastasis was detected in combination GEM + ZA
      treated mice compared to the control group (GEM + ZA; P = 0.005). CONCLUSIONS:
      The results of the present study indicate that ZA can selectively target
      metastasis in a pancreatic cancer PDOX model and that the combination of ZA and
      GEM should be evaluated clinically in the near future for this highly treatment
      resistant disease.

PMID- 25394370
TI  - Polarity of bacterial magnetotaxis is controlled by aerotaxis through a common
      sensory pathway.
AB  - Most motile bacteria navigate within gradients of external chemical stimuli by
      regulating the length of randomly oriented swimming episodes. Magnetotactic
      bacteria are characterized by chains of intracellular ferromagnetic nanoparticles
      and their ability to sense the geomagnetic field, which is believed to facilitate
      directed motion, but is not well understood at the behavioural and molecular
      level. Here, we show that cells of Magnetospirillum gryphiswaldense unexpectedly
      display swimming polarity that depends on aerotactic signal transduction through
      one of its four chemotaxis operons (cheOp1). Growth of cells in magnetic fields
      superimposed on oxygen gradients results in a gradual inherited bias of swimming
      runs with one of the cell poles leading, such that the resulting overall swimming
      direction of entire populations can be reversed by changes in oxygen
      concentration. These findings clearly show that there is a direct molecular link
      between aerotactic sensing and the determination of magnetotactic polarity,
      through the sensory pathway, CheOp1. 

PMID- 25394369
TI  - The association of polymorphisms of TLR4 and CD14 genes with susceptibility to
      sepsis in a Chinese population.
AB  - BACKGROUND: Sepsis is now the leading cause of death in the non-cardiovascular
      intensive care unit (ICU). Recent research suggests that sepsis is likely to be
      due to an interaction between genetic and environmental factors. Genetic
      mutations of toll-like receptor 4 (TLR4) and cluster of differentiation 14 (CD14)
      genes are involved in the immune and (or) inflammatory response. These may
      contribute to the susceptibility to sepsis in patients. This study was designed
      to evaluate whether the TLR4 and cluster CD14 gene polymorphisms are associated
      with susceptibility to sepsis. METHODS: The single nucleotide polymorphisms
      (SNPs) of TLR4 (rs10759932, rs11536889, rs7873784, rs12377632, rs1927907,
      rs1153879) and CD14 (rs2569190 and rs2563298) in patients with sepsis and control
      subjects in the Guangxi Province were analyzed by using the polymerase chain
      reaction-single base extension (PCR-SBE) and DNA sequencing methods. RESULTS: The
      rs11536889 polymorphism in TLR4 and rs2563298 polymorphism in CD14 were
      significantly associated with the risk of sepsis when compared to the control
      group. The frequencies of rs11536889 and rs2563298 polymorphisms in the group
      with sepsis were higher than that in the control group (OR = 1.430, 95% CI, 1.032
      1.981, P<0.05; OR = 2.454, 95% CI, 1.458-4.130, P<0.05, respectively). Followed
      up haplotype analysis suggested that there were two haplotypes in which increased
      risk factors for sepsis were indicated. CONCLUSIONS: The rs11536889 polymorphism
      in TLR4 and rs2563298 polymorphism in CD14, and two haplotypes were associated
      with increased susceptibility to sepsis.

PMID- 25394372
TI  - Changing times in the United Kingdom: The Centre for the Advancement of
      Interprofessional Education responds to the challenges.

PMID- 25394371
TI  - Adolescent health and adaptation in Canada: examination of gender and age aspects
      of the healthy immigrant effect.
AB  - INTRODUCTION: A longstanding and widely held assumption is that immigrants suffer
      from ill health and adaptation problems. Yet recent studies show that immigrants
      report the same or better state of health compared to their native-born
      counterparts. This phenomenon, known as the healthy immigrant effect, has been
      found in studies of specific health conditions of adults. The present study
      focuses instead on adolescents and extends its examination of the healthy
      immigrant effect, measuring both health and adaptation. METHODS: Using data from
      population samples in the Canadian Community Health Survey (2007), foreign-born
      immigrant adolescents (n = 920) were compared to non-immigrant adolescents (n =
      13,572) for their self-report to questionnaire items for health (general health,
      mental health, chronic illnesses with psychosomatic symptoms, and psychological
      illnesses) and adaptation (daily life stress, life satisfaction, and sense of
      belonging). Adolescents' gender, age, and length of residence were analyzed for
      the effects. RESULTS: Immigrant adolescents were better than non-immigrant peers
      on the four health measures, and did not differ from non-immigrants on the three
      adaptation measures despite having less household income and more family members
      in the household. Immigrant girls exhibited more resilient adaptability, while
      young immigrant boys and older non-immigrant girls displayed some potential
      vulnerability. Length of residence, on the other hand, did not contribute to
      differences for the health and adaptation of immigrant adolescents. CONCLUSIONS:
      The healthy immigrant effect was confirmed in a community population sample of
      adolescents in Canada. Foreign-born immigrant adolescents experience better
      health, as well as good adaptation equal to their native-born peers. These
      outcomes call for further research on sustaining good health and adaptation of
      the immigrant population, in particular by providing age-related effective
      services and prevention strategies.

PMID- 25394373
TI  - Psychiatric symptoms in vertiginous patients.
AB  - BACKGROUNDS: Psychiatric comorbidity is common in vertiginous patients. The risk
      of psychiatric disorder is increased in patients with previous mental problems,
      but earlier mentally healthy may develop symptoms as well. Especially in chronic
      phase of vertigo, psychological factors have a significant role in the morbidity.
      AIMS: The aim of this study was to evaluate the prevalence of psychiatric
      problems in vertiginous patients in a community sample. METHODS: A prospective
      evaluation of psychiatric symptoms based on self-rating scales [Beck Depression
      Inventory (BDI), Zung Anxiety Scale (SAS), DSM-IV and ICD-10 Personality
      Questionnaire (DIP-Q)] in a community sample of 100 vertiginous subjects in the
      Academic Tertiary Otolaryngology Department at the Helsinki University Hospital,
      Finland. RESULTS: The prevalence of any psychiatric problem was 68% (68
      patients); 19% had depressiveness and 12% symptoms of anxiety. Altogether 63
      (63%) patients met the criteria of personality disorder. The most prevalent
      personality disorder was obsessive-compulsive (46 patients). Personality disorder
      alone seems not to affect functional capacity and is of importance only when
      comorbid with symptoms of anxiety and depression. The prevalence of psychiatric
      symptoms did not correlate with severity of vertigo symptoms or other co
      occurring diseases. CONCLUSIONS: The prevalence of any psychiatric symptoms was
      high among vertiginous patients. In the chronic phase of vertigo, it seems that
      vertigo symptoms themselves do not influence on subjective feelings of
      debilitation. Psychiatric disorders worsen the clinical picture of vertigo along
      a more debilitating and disabling course. Psychiatric differential diagnoses
      should accompany the neuro-otology diagnostic procedure in patients with a
      chronic state of vertigo and greater disability.

PMID- 25394374
TI  - The catalytic asymmetric Abramov reaction.
AB  - The first catalytic enantioselective Abramov reaction is described. The process
      is based on the utilization of a chiral disulfonimide catalyst, which efficiently
      avoids the difficulties encountered with metal-based catalysts. Several
      functionalized alpha-hydroxy phosphonates were synthesized in good yields and
      with excellent enantiomeric ratios of up to >99:1. The process was shown to be
      scalable and up to 1 g of starting material could be employed under mild reaction
      conditions. 

PMID- 25394375
TI  - Exploring the meaning of recovery-oriented care: an action-research study.
AB  - The present study describes participants' perspectives of the meaning of recovery
      oriented care in developing services for people with psychosocial disability
      associated with mental illness. Participants were involved in a 12-month
      cooperative inquiry action-research group from August 2012 to July 2013, with six
      consumers, four clinicians, and a carer. A major finding was the importance of
      the facilitation of dialogue that acknowledged the asymmetrical power differences
      between participants. Thematically-analysed data identified an overarching global
      theme: 'I want services to hear me'. The theme reflected a shared view that
      participation is important in service development. Actions included mapping the
      integration of consumer participation within a mental health service and
      developing workshops to support change. Addressing the asymmetrical power
      relationship inherent in traditional mental health design is important. Using
      participatory processes, structural discrimination is revealed, and tensions
      associated with clinical mental health services and psychiatric practice can be
      discussed. A partnership approach to service development enables the social
      determinants of health to be addressed more effectively, as well as supporting
      individual recovery. These approaches create the potential for genuine
      transformational change. Approaches that support coproduction and codesign have
      the potential to enable solutions. 

PMID- 25394376
TI  - Age, insulin requirements, waist circumference, and triglycerides predict
      hypogonadotropic hypogonadism in patients with type 1 diabetes.
AB  - INTRODUCTION: The prevalence of hypogonadotropic hypogonadism (HH) in patients
      with type 2 diabetes mellitus is higher than in the general population and leads
      to detrimental effects on metabolic control, lipid profile, and body composition.
      Few studies have examined its role in type 1 diabetes mellitus. AIM: To determine
      the prevalence of HH in patients with type 1 diabetes and associated risk
      factors. MAIN OUTCOME MEASURES: Clinical and biochemical parameters were gathered
      on initial evaluation. An HH score creating different experimental models was
      devised to calculate the risk of HH for an individual with type 1 diabetes.
      METHODS: Cross-sectional study of 181 male patients with type 1 diabetes
      consecutively admitted to the Diabetes outpatient clinics of three urban
      hospitals. All participants were Caucasians aged >= 18 years with type 1 diabetes
      duration of more than 6 months. RESULTS: One hundred and eighty-one male patients
      with a mean age of 44.2 +/- 13.2 years and a type 1 diabetes duration of 18.9 +/-
      12.7 years were included. Fifteen patients had HH, representing a prevalence of
      8.3% (95% confidence interval [CI]: 4.3-12.3%). Age (odds ratio [OR] 1.066 [95%
      CI: 1.002-1.134]), waist circumference (OR 1.112 [95% CI: 1028-1203]), and
      insulin requirements ([IU/Kg] *10 [OR 1.486 {95% CI: 1052-2.098}]) were
      independently associated with the presence of HH. The model that best predicted
      HH generated this formula: HH-score = (1.060 * age) + (1.084 * waist
      circumference) + (14.00 * insulin requirements) + triglycerides, where age was
      expressed in years, waist circumference in cm, insulin requirements in IU/kg/d,
      and triglycerides in mg/dL. An HH score > 242.4 showed 100% sensitivity and 53.2%
      specificity for HH diagnosis; positive and negative predictive values were 17.0 %
      and 100%, respectively. CONCLUSIONS: One in 10 men with type 1 diabetes presents
      HH. This condition is associated with age, waist circumference, and insulin
      requirements. A simple formula based on clinical parameters can rule out its
      presence.

PMID- 25394377
TI  - A novel concept for continuous peripheral nerve blocks. Presentation of a new
      ultrasound-guided device.
AB  - BACKGROUND: Existing techniques for placing and maintaining the position of
      peripheral nerve catheters are associated with variable success rates and
      frequent secondary failures. These factors may affect the clinical efficacy and
      usefulness of peripheral nerve catheters. METHODS: We developed a new concept and
      prototype for ultrasound-guided in-plane positioning and readjustment of
      peripheral nerve catheters (patent pending). The integrated catheter-needle
      prototype comprises three parts: a curved needle, a catheter with clear echogenic
      markings attached to the needle tail and a detachable hub allowing injection of
      local anesthetic while advancing the needle in the tissue. The system works like
      a suture and is introduced through the skin, passes in close relation to the
      nerve and exits through the skin. This allows in-plane ultrasound guidance
      throughout the procedure both during initial positioning as well as during later
      in-plane readjustment of the catheter. We tested the system in the popliteal
      region of two fresh cadavers in a preliminary proof of concept study. RESULTS:
      Both initial placement and secondary readjustment were precise, judged by the
      catheter orifices placed close to the sciatic nerve in the popliteal fossa.
      Circumferential spread of 3-ml isotonic saline around the sciatic nerve was
      observed on ultrasound images in both conditions. CONCLUSION: Preliminary proof
      of concept of this novel method demonstrates that precise in-plane ultrasound
      guided initial placement and secondary in-plane readjustment is possible in fresh
      cadavers. Future studies should address the clinical efficacy and usefulness of
      this novel concept.

PMID- 25394378
TI  - Use of CTLA4Ig for induction of mixed chimerism and renal allograft tolerance in
      nonhuman primates.
AB  - We have previously reported successful induction of renal allograft tolerance via
      a mixed chimerism approach in nonhuman primates. In those studies, we found that
      costimulatory blockade with anti-CD154 mAb was an effective adjunctive therapy
      for induction of renal allograft tolerance. However, since anti-CD154 mAb is not
      clinically available, we have evaluated CTLA4Ig as an alternative agent for
      effecting costimulation blockade in this treatment protocol. Two CTLA4Igs,
      abatacept and belatacept, were substituted for anti-CD154 mAb in the conditioning
      regimen (low dose total body irradiation, thymic irradiation, anti-thymocyte
      globulin and a 1-month posttransplant course of cyclosporine [CyA]). Three
      recipients treated with the abatacept regimen failed to develop comparable
      lymphoid chimerism to that achieved with anti-CD154 mAb treatment and these
      recipients rejected their kidney allografts early. With the belatacept regimen,
      four of five recipients developed chimerism and three of these achieved long-term
      renal allograft survival (>861, >796 and >378 days) without maintenance
      immunosuppression. Neither chimerism nor long-term allograft survival were
      achieved in two recipients treated with the belatacept regimen but with a lower,
      subtherapeutic dose of CyA. This study indicates that CD28/B7 blockade with
      belatacept can provide a clinically applicable alternative to anti-CD154 mAb for
      promoting chimerism and renal allograft tolerance. 

PMID- 25394380
TI  - G206D Mutation of Presenilin-1 Reduces Pen2 Interaction, Increases
      Abeta42/Abeta40 Ratio and Elevates ER Ca(2+) Accumulation.
AB  - Early-onset familial Alzheimer's disease (AD) is most commonly associated with
      the mutations in presenilin-1 (PS1). PS1 is the catalytic component of the gamma
      secretase complex, which cleaves amyloid precursor protein to produce amyloid
      beta (Abeta), the major cause of AD. Presenilin enhancer 2 (Pen2) is critical for
      activating gamma-secretase and exporting PS1 from endoplasmic reticulum (ER).
      Among all the familial AD-linked PS1 mutations, mutations at the G206 amino acid
      are the most adjacent position to the Pen2 binding site. Here, we characterized
      the effect of a familial AD-linked PS1 G206D mutation on the PS1-Pen2 interaction
      and the accompanied alteration in gamma-secretase-dependent and -independent
      functions. We found that the G206D mutation reduced PS1-Pen2 interaction, but did
      not abolish gamma-secretase formation and PS1 endoproteolysis. For gamma
      secretase-dependent function, the G206D mutation increased Abeta42 production but
      not Notch cleavage. For gamma-secretase-independent function, this mutation
      disrupted the ER calcium homeostasis but not lysosomal calcium homeostasis and
      autophagosome maturation. Impaired ER calcium homeostasis may due to the reduced
      mutant PS1 level in the ER. Although this mutation did not alter the cell
      survival under stress, both increased Abeta42 ratio and disturbed ER calcium
      regulation could be the mechanisms underlying the pathogenesis of the familial AD
      linked PS1 G206D mutation.

PMID- 25394381
TI  - Ameliorative Effects of p75NTR-ED-Fc on Axonal Regeneration and Functional
      Recovery in Spinal Cord-Injured Rats.
AB  - As a co-receptor of Nogo-66 receptor (NgR) and a critical receptor for paired
      immunoglobulin-like receptor (PirB), p75 neurotrophin receptor (p75NTR) mediates
      the inhibitory effects of myelin-associated inhibitors on axonal regeneration
      after spinal cord injury. Therefore, the p75NTR antagonist, such as recombinant
      p75NTR protein or its homogenates may block the inhibitory effects of myelin and
      promote the axonal regeneration and functional recovery. The purposes of this
      study are to subclone and express the extracellular domain gene of human p75NTR
      with IgG-Fc (hp75NTR-ED-Fc) in prokaryotic expression system and investigate the
      effects of the recombinant protein on axonal regeneration and functional recovery
      in spinal cord-injured rats. The hp75NTR-ED-Fc coding sequence was amplified from
      pcDNA-hp75NTR-ED-Fc by polymerase chain reaction (PCR) and subcloned into vector
      pET32a (+), then the effects of the purified recombinant protein on neurite
      outgrowth of dorsal root ganglion (DRG) neurons cultured with myelin-associated
      glycoprotein (MAG) were determined, and the effects of the fusion protein on
      axonal regeneration, functional recovery, and its possible mechanisms in spinal
      cord-injured rats were further investigated. The results indicated that the
      purified infusion protein could promote neurite outgrowth of DRG neurons, promote
      axonal regeneration and functional recovery, and decrease RhoA activation in
      spinal cord-injured rats. Taken together, the findings revealed that p75NTR still
      may be a potential and novel target for therapeutic intervention for spinal cord
      injury and that the hp75NTR-ED-Fc fusion protein treatment enhances functional
      recovery by limiting tissue loss and stimulating axonal growth in spinal cord
      injured rats, which may result from decreasing the activation of RhoA. 

PMID- 25394379
TI  - MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine
      Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic
      Treatment Under a Theranostic Perspective.
AB  - Despite dopamine-glutamate aberrant interaction that has long been considered a
      relevant landmark of psychosis pathophysiology, several aspects of these two
      neurotransmitters reciprocal interaction remain to be defined. The emerging role
      of postsynaptic density (PSD) proteins at glutamate synapse as a molecular "lego"
      making a functional hub where different signals converge may add a new piece of
      information to understand how dopamine-glutamate interaction may work with regard
      to schizophrenia pathophysiology and treatment. More recently, compelling
      evidence suggests a relevant role for microRNA (miRNA) as a new class of dopamine
      and glutamate modulators with regulatory functions in the reciprocal interaction
      of these two neurotransmitters. Here, we aimed at addressing the following
      issues: (i) Do miRNAs have a role in schizophrenia pathophysiology in the context
      of dopamine-glutamate aberrant interaction? (ii) If miRNAs are relevant for
      dopamine-glutamate interaction, at what level this modulation takes place? (iii)
      Finally, will this knowledge open the door to innovative diagnostic and
      therapeutic tools? The biogenesis of miRNAs and their role in synaptic plasticity
      with relevance to schizophrenia will be considered in the context of dopamine
      glutamate interaction, with special focus on miRNA interaction with PSD elements.
      From this framework, implications both for biomarkers identification and
      potential innovative interventions will be considered. 

PMID- 25394382
TI  - Guanosine Protects Against Cortical Focal Ischemia. Involvement of Inflammatory
      Response.
AB  - Stroke is the major cause of death and the most frequent cause of disability in
      the adult population worldwide. Guanosine plays an important neuroprotective role
      in several cerebral ischemic models and is involved in the modulation of
      oxidative responses and glutamatergic parameters. Because the excessive reactive
      oxygen species produced during an ischemic event can trigger an inflammatory
      response, the purpose of this study was to evaluate the hypothesis that guanosine
      is neuroprotective against focal cerebral ischemia, inhibits
      microglia/macrophages activation, and mediates an inflammatory response
      ameliorating the neural damage. Permanent focal cerebral ischemia was induced in
      adult rats, and guanosine was administered immediately, 1, 3, and 6 h after
      surgery. Twenty-four hours after ischemia, the asymmetry scores were evaluated by
      the cylinder test; neuronal damage was evaluated by Fluoro-Jade C (FJC) staining
      and propidium iodide (PI) incorporation; microglia and immune cells were
      evaluated by anti-Iba-1 antibody; and inflammatory parameters such as
      interleukins (IL): IL-1, IL-6, IL-10; tumor necrosis factors alpha (TNF-alpha);
      and interferon-gamma (INF-gamma) were evaluated in the brain tissue and
      cerebrospinal fluid. The ischemic event increased the levels of Iba-1-positive
      cells and pro-inflammatory cytokines and decreased IL-10 levels (an anti
      inflammatory cytokine) in the lesion periphery. The guanosine treatment
      attenuated the changes in these inflammatory parameters and also reduced the
      infarct volume, PI incorporation, and number of FJC-positive cells, improving the
      functional recovery. Thus, guanosine may have been a promising therapeutic agent
      for the treatment of ischemic brain injury by reduction of inflammatory process
      triggered in an ischemic event.

PMID- 25394383
TI  - The Upshot of LRRK2 Inhibition to Parkinson's Disease Paradigm.
AB  - Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are implicated in
      autosomal dominant familial and sporadic Parkinson's disease (sPD). Given its
      relative frequency in PD and its putative function in several cellular pathways
      that are known to be impaired in the disease, we wanted to tackle LRRK2
      physiological role and to address its potential as a PD therapeutic target. We
      investigated the impact of pharmacological inhibition of LRRK2 kinase activity in
      control and PD cell function. We provide evidence that physiologically LRRK2,
      through its kinase activity, regulates mitochondrial fission events and
      facilitates autophagic degradation by modulating lysosomal cellular localization.
      Upon LRRK2 inhibition, normal fission decreases, leading to the elongation of
      mitochondrial network which contributes to a poor degradation of deficient
      mitochondria. Moreover, LRRK2 inhibition promotes lysosomal perinuclear
      clustering, through Rab7 that further hinders autophagosomes degradation. These
      events induce a decrease in the autophagic flow, which contributed directly to a
      decreased proteolytic degradation of damaged mitochondria. These data resembled
      the results observed in sPD cells. Interestingly, the LRRK2 kinase activity is
      increased in sPD cells, and despite its inhibition recovers mitochondrial
      cellular localization, it did not improve microtubule network-dependent
      trafficking. Our results provide novel insights into the multiple mechanisms that
      dictate the association between LRRK2 and mitophagy in sPD, and contribute with
      new findings that could have important therapeutic implications. 

PMID- 25394385
TI  - Current status of management of malignant disease: what are the options for
      premalignant lesions of the esophagus and stomach?
AB  - INTRODUCTION: Premalignant lesions of the foregut (esophagus and stomach) are
      common entities usually incidentally identified on either endoscopic or
      radiographic imaging studies. SYMPTOMS: These lesions are often asymptomatic or
      associated with vague gastrointestinal symptoms. TREATMENT: Current management of
      benign and premalignant lesions of the foregut includes primarily ablative and
      resective endoscopic techniques as well as thoracoscopic, laparoscopic, and open
      surgical techniques of enucleation and segmental resections. The appropriate
      procedure, however, is based on the depth of penetration, lesion location, and
      suspicion for underlying malignant potential.

PMID- 25394384
TI  - MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy.
AB  - Emerging evidence indicates that certain microRNAs (miRNAs) play important roles
      in epileptogenesis. MiR-219 is a brain-specific miRNA and has been shown to
      negatively regulate the function of N-methyl-D-aspartate (NMDA) receptors by
      targeting Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)gamma. Herein, we
      found that the level of miR-219 was decreased in both the kainic acid (KA)
      induced epilepsy model and in cerebrospinal fluid specimens of epilepsy patients.
      Importantly, silencing of miR-219 by its antagomir in vivo resulted in seizure
      behaviors, abnormal cortical electroencephalogram (EEG) recordings in the form of
      high-amplitude and high-frequency discharges, and increased levels of CaMKIIgamma
      and an NMDA receptor component, NR1, in a pattern similar to that found in KA
      treated mice. Moreover, treatments with the miR-219 agomir in vivo alleviated
      seizures, abnormal EEG recordings, and decreased levels of CaMKIIgamma and NR1 in
      KA-treated mice. Furthermore, treatment with MK-801, an antagonist of NMDA
      receptors, significantly alleviated abnormal EEG recordings induced by miR-219
      antagomir. Together, these results demonstrate that miR-219 plays a crucial role
      in suppressing seizure formation in experimental models of epilepsy through
      modulating the CaMKII/NMDA receptor pathway and that miR-219 supplement may be a
      potential anabolic strategy for ameliorating epilepsy. 

PMID- 25394386
TI  - Prognostic significance of metastatic lymph node number, ratio and station in
      gastric neuroendocrine carcinoma.
AB  - The objective of this study was to analyze the prognostic significance of
      metastatic lymph node status in gastric neuroendocrine carcinoma (GNEC) patients
      following radical gastrectomy. A consecutive series of 73 patients who underwent
      gastrectomy between 1999 and 2011 for GNEC was retrospectively reviewed. Indexes
      of lymph node involvement (the pN classification, metastatic lymph node number
      [MLNn], ratio [MLNr], and station [MLNs]) and other clinicopathological data were
      analyzed. Fifty-four patients met the inclusion criteria and were enrolled in the
      study. Among them, 44 patients (81 %) were found to have lymph node metastases.
      The median survival time of the entire cohort was 63.2 (range, 14-153) months
      with 3- and 5-year survival rates of 88.9 and 47.9 %, respectively. The median
      total number of lymph nodes, MLNn, and MLNr were 19 (range, 10-56), 5 (range, 1
      21), and 25 % (6-100 %), respectively. Cox regression analysis revealed pN
      classification = 1, MLNn >2, MLNr >0.1, and MLNs = 2, and distant metastases
      influenced prognosis independently (P = 0.0266, 0.0091, 0.0031, 0.0119, and
      0.0021, respectively). In addition to the pN classification, indexes of
      metastatic lymph node involvement, including MLNn, MLNr, and MLNs, were all
      significant predictors of survival in GNEC patients. Distant metastasis was also
      a significant prognostic factor. These indexes proved to be accurate and
      important supplements to survival factors, which may improve risk classification
      of GNEC patients.

PMID- 25394387
TI  - Robotic versus laparoscopic total mesorectal excision for rectal cancer: a meta
      analysis of eight studies.
AB  - BACKGROUND: Robotic surgery has been used successfully in many branches of
      surgery, but there is little evidence in the literature on its use in rectal
      cancer (RC). We conducted this meta-analysis of randomized controlled trials
      (RCTs) and non-randomized controlled trials (NRCTs) to evaluate whether the
      safety and efficacy of robotic total mesorectal excision (RTME) in patients with
      RC are equivalent to those of laparoscopic TME (LTME). METHODS: Pubmed, Embase,
      Cochrane Library, Ovid, and Web of Science databases were searched. Studies
      clearly documenting a comparison of RTME with LTME for RC were selected.
      Operative and recovery outcomes, early postoperative morbidity, and oncological
      parameters were evaluated. RESULTS: Eight studies were identified that included
      1229 patients in total, 554 (45.08 %) in the RTME group and 675 (54.92 %) in the
      LTME group. Compared with LTME, RTME was associated with lower conversion rate
      (OR 0.23, 95 % CI [0.10, 0.52]; P = 0.0004), lower positive rate of
      circumferential resection margins (CRM) (2.74 % vs 5.78 %, OR 0.44, 95 % CI
      [0.20, 0.96], P = 0.04), and lesser incidence of erectile dysfunction (ED) (OR
      0.09, 95 % CI [0.02, 0.41]; P = 0.002). Operation time, estimated blood loss,
      recovery outcome, postoperative morbidity and mortality, length of hospital stay,
      number of lymph nodes harvested, distal resection margin (DRM), proximal
      resection margin (PRM), and local recurrence had no significant differences
      between the two groups. CONCLUSIONS: RTME is safe and feasible and may be an
      alternative treatment for RC. More international multicenter prospective large
      sample RCTs investigating the long-term oncological and functional outcomes are
      needed to determine the advantages of RTME over LTME in RC.

PMID- 25394389
TI  - A biomimetic heteroditopic receptor for zwitterions in protic media.
AB  - The efficient synthesis of calix[6]cryptothiourea 6 was achieved through a two
      step sequence that involves a key [1+1] macrocyclization step. It was shown by
      NMR spectroscopy that this heteroditopic receptor can bind zwitterions in protic
      media with an outstanding selectivity for beta-alanine betaine G5, which is
      likely due to a high complementarity between the two partners. This result
      constitutes a rare example of cavity complexation of a zwitterion by a
      calix[6]arene. In comparison with the parent urea-based receptors, 6 behaves as a
      much more efficient host for betaines. This strengthening of the binding
      properties is due to the better preorganization of the tripodal hydrogen-bonding
      cap as well as to the higher acidity of the thiourea groups and their poor
      ability to self-associate. Remarkably, host 6 is able to perform solid-liquid as
      well as liquid-liquid extraction of G5. Finally, 6 provides an excellent
      structural model for the binding site of glycine betaine G4 encountered in
      natural systems. 

PMID- 25394388
TI  - The toxic effect of R350P mutant desmin in striated muscle of man and mouse.
AB  - Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant,
      autosomal recessive and sporadic forms of protein aggregation myopathies and
      cardiomyopathies. We generated R349P desmin knock-in mice, which harbor the
      ortholog of the most frequently occurring human desmin missense mutation R350P.
      These mice develop age-dependent desmin-positive protein aggregation pathology,
      skeletal muscle weakness, dilated cardiomyopathy, as well as cardiac arrhythmias
      and conduction defects. For the first time, we report the expression level and
      subcellular distribution of mutant versus wild-type desmin in our mouse model as
      well as in skeletal muscle specimens derived from human R350P desminopathies.
      Furthermore, we demonstrate that the missense-mutant desmin inflicts changes of
      the subcellular localization and turnover of desmin itself and of direct desmin
      binding partners. Our findings unveil a novel principle of pathogenesis, in which
      not the presence of protein aggregates, but disruption of the extrasarcomeric
      intermediate filament network leads to increased mechanical vulnerability of
      muscle fibers. These structural defects elicited at the myofiber level finally
      impact the entire organ and subsequently cause myopathy and cardiomyopathy. 

PMID- 25394390
TI  - Current controversies in prenatal diagnosis 2: prediction and prevention of
      adverse pregnancy outcomes requires a genomic rather than proteomic solution.
AB  - From both presentations, it is clear that understanding the APO associated with
      placental dysfunction represents one of the greatest challenges in the field of
      prenatal screening, diagnosis, and therapy. Their clinical impact on the health
      of the mother and child was well recognized by the debaters, and both have agreed
      that there is a paucity of knowledge in the etiophysiopathology of placental
      dysfunction and the associated clinical phenotypes. They also agreed that this
      marked limitation in our understanding is a significant problem when designing a
      research protocol, and both stressed the importance of proper study designs. When
      focusing on the specific topics of the debate, they showed different opinions
      about the role of genomics in the search for relevant answers. Leslie Myatt
      pointed out that the genome does not define the cellular phenotype, and although
      the proteome itself does not define phenotype, it is much closer to it than the
      genome. Conversely, Rossa Chiu suggested that genomic approaches offer a better
      chance of achieving the answers than by proteomics alone. Actually, she
      hypothesized that through genomic approaches, or rather through systems biology,
      that is, including genomics, epigenomics, transcriptomics, and proteomics, there
      would be a better chance of obtaining the best answers. She also raised the
      possibility of the potential use of cell-free fetal nucleic acids in maternal
      plasma, which in turn are mainly of placental origin. Finally, both debaters and
      the audience agreed that there was not an exclusive proteomic or genomic
      'solution', but that we need a larger spectrum of research strategies to include
      both proteomics and genomics and other systems biology approaches, combined with
      detailed and standardized clinical, laboratory, and epidemiological criteria in
      appropriately designed studies in order to start filling the significant gaps in
      our knowledge about this highly complex area of placental mediated adverse
      pregnancy outcomes.

PMID- 25394391
TI  - Case of vascular air embolism during holmium laser enucleation of the prostate.
AB  - Vascular air embolism is a rare complication during transurethral surgery. A case
      of air embolism during holmium laser enucleation of the prostate in a 76-year-old
      man is presented. During the step of morcellation, the patient's blood pressure
      suddenly oscillated up and down, and end-tidal CO2 and arterial saturation
      decreased. Transesophageal and transthoracic echocardiography showed air
      collection in the right atrium. It was also discovered that incorrect assembly of
      the tube from the morcellator caused rapid entrainment of air into the vein.
      Computed tomography and abdominal X-ray showed niveau formation in the femoral
      vein and air collection in the pelvic retroperitoneal space. The patient
      recovered with careful observation and was discharged 7 days after the operation
      with no sequelae. This report is presented to remind urologists of this unusual
      complication that can occur during holmium laser enucleation of the prostate
      procedures. 

PMID- 25394393
TI  - Throughfall under a teak plantation in Thailand: a multifactorial analysis on the
      effects of canopy phenology and meteorological conditions.
AB  - Valuable teak (Tectona grandis Linn. f.) plantations cover vast areas throughout
      Southeast Asia. This study sought to increase our understanding of throughfall
      inputs under teak by analyzing the abiotic and biotic factors governing
      throughfall amounts and ratios in relation to three canopy phenophases (leafless,
      leafing, and leafed). There was no rain during the brief leaf senescence
      phenophase in our study. Leveraging detailed field observations, we employed
      boosted regression tree (BRT) analysis to identify the primary controls on
      throughfall amount and ratio during each canopy phenophase. Whereas throughfall
      amounts were always dominated by rainfall magnitude (as expected), throughfall
      ratios were governed by a suite of predictor variables during each phenophase.
      The BRT analysis demonstrated that throughfall ratio in the leafless phase was
      most influenced (in descending order of importance) by air temperature, rainfall
      amount, maximum wind speed, and rainfall intensity. Throughfall ratio in the
      leafed phenophase was dominated by rainfall amount. The leafing phenophase was an
      intermediate case where rainfall amount, air temperature, and vapor pressure
      deficit were most important. Our results highlight the fact that throughfall
      ratios are differentially influenced by a suite of meteorological variables
      during each canopy phenophase. Abiotic variables, such as rainfall amount and air
      temperature, trumped leaf area index and stand density in their effect on
      throughfall ratio. The leafing phenophase, while transitional in nature and short
      in duration, has a detectable and unique impact on water inputs to teak
      plantations. Further work is needed to better understand the biogeochemistry of
      leaf emergence in teak plantations. 

PMID- 25394392
TI  - Susceptibility to deltamethrin of wild and domestic populations of Triatoma
      infestans of the Gran Chaco and the Inter-Andean Valleys of Bolivia.
AB  - BACKGROUND: The persistence of Triatoma infestans and the continuous transmission
      of Trypanosoma cruzi in the Inter-Andean Valleys and in the Gran Chaco of Bolivia
      are of great significance. Coincidentally, it is in these regions the reach of
      the vector control strategies is limited, and reports of T. infestans resistance
      to insecticides, including in wild populations, have been issued. This study aims
      to characterize the susceptibility to deltamethrin of wild and domestic
      populations of T. infestans from Bolivia, in order to better understand the
      extent of this relevant problem. METHODS: Susceptibility to deltamethrin was
      assessed in nine, wild and domestic, populations of T. infestans from the Gran
      Chaco and the Inter-Andean Valleys of Bolivia. Serial dilutions of deltamethrin
      in acetone (0.2 MUL) were topically applied in first instar nymphs (F1, five days
      old, fasting, weight 1.2 +/- 0.2 mg). Dose response results were analyzed with
      PROBIT version 2, determining the lethal doses, slope and resistance ratios (RR).
      Qualitative tests were also performed. RESULTS: Three wild T. infestans dark
      morph samples of Chaco from the Santa Cruz Department were susceptible to
      deltamethrin with RR50 of <2, and 100% mortality to the diagnostic dose (DD);
      however, two domestic populations from the same region were less susceptible than
      the susceptibility reference lineage (RR50 of 4.21 and 5.04 respectively and 93%
      DD). The domestic population of Villa Montes from the Chaco of the Tarija
      Department presented high levels of resistance (RR50 of 129.12 and 0% DD).
      Moreover, the domestic populations from the Valleys of the Cochabamba Department
      presented resistance (RR50 of 8.49 and 62% DD), the wild populations were less
      susceptible than SRL and T. infestans dark morph populations (RR50 < 5).
      CONCLUSION: The elimination of T. infestans with pyrethroid insecticides in
      Brazil, Uruguay, Chile, and its drastic reduction in large parts of Paraguay and
      Argentina, clearly indicates that pyrethroid resistance was very uncommon in non
      Andean regions. The pyrethroid susceptibility of non-Andean T. infestans dark
      morph population, and the resistance towards it, of Andean T. infestans wild and
      domestic populations, indicates that the Andean populations from Bolivia are less
      susceptible.

PMID- 25394394
TI  - Placement of temperature probe in bovine vagina for continuous measurement of
      core-body temperature.
AB  - There has been increasing interest to measure core-body temperature in cattle
      using internal probes. This study examined the placement of HOBO water
      temperature probe with an anchor, referred to as the "sensor pack" (Hillman et
      al. Appl Eng Agric ASAE 25(2):291-296, 2009) in the vagina of multiparous
      Holstein cows under grazing conditions. Two types of anchors were used: (a) long
      "fingers" (4.5-6 cm), and (b) short "fingers" (3.5 cm). The long-finger anchors
      stayed in one position while the short-finger anchors were not stable in one
      position (rotate) within the vagina canal and in some cases came out. Vaginal
      temperatures were recorded every minute and the data collected were then analyzed
      using exponential mixed model regression for non-linear data. The results showed
      that the core-body temperatures for the short-finger anchors were lower than the
      long-finger anchors. This implied that the placement of the temperature sensor
      within the vagina cavity may affect the data collected.

PMID- 25394395
TI  - Influence of Panax ginseng on the offspring of adult rats exposed to prenatal
      stress.
AB  - The exposure of pregnant females to stress during a critical period of fetal
      brain development is an environmental risk factor for the development of
      schizophrenia in adult offspring. Schizophrenia is a group of common mental
      disorders of unclear origin, affecting approximately 1% of the global population,
      showing a generally young age at onset. In the present study, a repeated variable
      stress paradigm was applied to pregnant rats during the final week of gestation.
      The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to
      prenatal stress (PNS) were investigated in terms of behavioral activity and
      protein expression analyses. In the behavioral tests, grooming behavior in a
      social interaction test, line-crossing behavior in an open-field test and
      swimming activity in a forced-swim test were decreased in the rats exposed to PNS
      compared with the non-stressed offspring; the changes in behavioral activity were
      reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot
      analysis and immunohistochemical analyses of the prefrontal cortex and
      hippocampus revealed that the downregulation of several neurodevelopmental genes
      which occurred following exposure to PNS was reversed upon treatment with PG. The
      current findings demonstrate that the downregulation of several genes following
      exposure to PNS may affect subsequent behavioral changes, and that these
      phenomena are reversed following treatment with PG during pregnancy. Our results
      suggest that oral treatment with PG reduces the incidence of psychiatric
      disorders, such as schizophrenia.

PMID- 25394396
TI  - Effect of the cognitive-motor dual-task using auditory cue on balance of
      surviviors with chronic stroke: a pilot study.
AB  - OBJECTIVE: To investigate the effect of a cognitive-motor dual-task using
      auditory cues on the balance of patients with chronic stroke. DESIGN: Randomized
      controlled trial. SETTING: Inpatient rehabilitation center. SUBJECTS: Thirty
      seven individuals with chronic stroke. INTERVENTIONS: The participants were
      randomly allocated to the dual-task group (n=19) and the single-task group
      (n=18). The dual-task group performed a cognitive-motor dual-task in which they
      carried a circular ring from side to side according to a random auditory cue
      during treadmill walking. The single-task group walked on a treadmill only. All
      subjects completed 15 min per session, three times per week, for four weeks with
      conventional rehabilitation five times per week over the four weeks. MAIN
      MEASURES: Before and after intervention, both static and dynamic balance were
      measured with a force platform and using the Timed Up and Go (TUG) test. RESULTS:
      The dual-task group showed significant improvement in all variables compared to
      the single-task group, except for anteroposterior (AP) sway velocity with eyes
      open and TUG at follow-up: mediolateral (ML) sway velocity with eye open (dual
      task group vs. single-task group: 2.11 mm/s vs. 0.38 mm/s), ML sway velocity with
      eye close (2.91 mm/s vs. 1.35 mm/s), AP sway velocity with eye close (4.84 mm/s
      vs. 3.12 mm/s). After intervention, all variables showed significant improvement
      in the dual-task group compared to baseline. CONCLUSION: The study results
      suggest that the performance of a cognitive-motor dual-task using auditory cues
      may influence balance improvements in chronic stroke patients.

PMID- 25394397
TI  - The effects of aquatic therapy on mobility of individuals with neurological
      diseases: a systematic review.
AB  - OBJECTIVE: To summarize evidence on the effects of aquatic therapy on mobility in
      individuals with neurological diseases. DATA SOURCES: MEDLINE, EMBASE, PsycInfo,
      CENTRAL, CINAHL, SPORTDiscus, PEDro, PsycBITE and OT Seeker were searched from
      inception to 15 September 2014. Hand-searching of reference lists was performed
      in the selected studies. REVIEW METHODS: The search included randomized
      controlled trials and quasi-experimental studies that investigated the use of
      aquatic therapy and its effect on mobility of adults with neurological diseases.
      One reviewer screened titles and abstracts of retrieved studies from the search
      strategy. Two reviewers independently examined the full texts and conducted the
      study selection, data extraction and quality assessment. A narrative synthesis of
      data was applied to summarize information from included studies. The Downs and
      Black Scale was used to assess methodological quality. RESULTS: A total of 116
      articles were obtained for full text eligibility. Twenty studies met the
      specified inclusion criteria: four Randomized Controlled Trials (RCTs), four non
      randomized studies and 12 before-and-after tests. Two RCTs (30 patients with
      stroke in the aquatic therapy groups), three non-randomized studies and three
      before-and-after studies showed "fair" evidence that aquatic therapy increases
      dynamic balance in participants with some neurological disorders. One RCT (seven
      patients with stroke in the aquatic therapy group) and two before-and-after tests
      (20 patients with multiple sclerosis) demonstrated "fair" evidence on improvement
      of gait speed after aquatic therapy. CONCLUSION: Our synthesis showed "fair"
      evidence supporting the use of aquatic therapy to improve dynamic balance and
      gait speed in adults with certain neurological conditions.

PMID- 25394398
TI  - Hepatic proteome analysis of Atlantic salmon (Salmo salar) after exposure to
      environmental concentrations of human pharmaceuticals.
AB  - Pharmaceuticals are pseudopersistent aquatic pollutants with unknown effects at
      environmentally relevant concentrations. Atlantic salmon (Salmo salar) were
      exposed to Acetaminophen: 54.77 +/- 34.67; Atenolol: 11.08 +/- 7.98, and
      Carbamazepine: 7.85 +/- 0.13 MUg.L(-1) for 5 days. After Acetaminophen treatment,
      19 proteins were differently expressed, of which 11 were significant with respect
      to the control group (eight up-regulated and three down-regulated). After
      Atenolol treatment, seven differently expressed proteins were obtained in
      comparison with the control, of which six could be identified (four up-regulated
      and two down-regulated). Carbamazepine exposure resulted in 15 differently
      expressed proteins compared with the control, with 10 of them identified (seven
      up-regulated and three down-regulated). Out of these, three features were common
      between Acetaminophen and Carbamazepine and one between Carbamazepine and
      Atenolol. One feature was common across all treatments. Principal component
      analysis and heat map clustering showed a clear grouping of the variability
      caused by the applied treatments. The obtained data suggest (1) that exposure to
      environmentally relevant concentrations of the pharmaceuticals alters the hepatic
      protein expression profile of the Atlantic salmon; and (2) the existence of
      treatment specific processes that may be useful for biomarker development. 

PMID- 25394399
TI  - Comprehensive and reproducible phosphopeptide enrichment using iron immobilized
      metal ion affinity chromatography (Fe-IMAC) columns.
AB  - Advances in phosphopeptide enrichment methods enable the identification of
      thousands of phosphopeptides from complex samples. Current offline enrichment
      approaches using TiO(2), Ti, and Fe immobilized metal ion affinity chromatography
      (IMAC) material in batch or microtip format are widely used, but they suffer from
      irreproducibility and compromised selectivity. To address these shortcomings, we
      revisited the merits of performing phosphopeptide enrichment in an HPLC column
      format. We found that Fe-IMAC columns enabled the selective, comprehensive, and
      reproducible enrichment of phosphopeptides out of complex lysates. Column
      enrichment did not suffer from bead-to-sample ratio issues and scaled linearly
      from 100 MUg to 5 mg of digest. Direct measurements on an Orbitrap Velos mass
      spectrometer identified >7500 unique phosphopeptides with 90% selectivity and
      good quantitative reproducibility (median cv of 15%). The number of unique
      phosphopeptides could be increased to more than 14,000 when the IMAC eluate was
      subjected to a subsequent hydrophilic strong anion exchange separation. Fe-IMAC
      columns outperformed Ti-IMAC and TiO(2) in batch or tip mode in terms of
      phosphopeptide identification and intensity. Permutation enrichments of flow
      throughs showed that all materials largely bound the same phosphopeptide species,
      independent of physicochemical characteristics. However, binding capacity and
      elution efficiency did profoundly differ among the enrichment materials and
      formats. As a result, the often quoted orthogonality of the materials has to be
      called into question. Our results strongly suggest that insufficient capacity,
      inefficient elution, and the stochastic nature of data-dependent acquisition in
      mass spectrometry are the causes of the experimentally observed complementarity.
      The Fe-IMAC enrichment workflow using an HPLC format developed here enables rapid
      and comprehensive phosphoproteome analysis that can be applied to a wide range of
      biological systems.

PMID- 25394400
TI  - Benchmarking coupled cluster methods on singlet excited states of nucleobases.
AB  - In this paper, coupled cluster methods CC2, CCSD, CCSDR(3) and EOM-CCSD(T) have
      been benchmarked against CC3 for the transition energies of nucleobases. Beside
      presenting vertical excitation energies for about 30 singlet transitions of four
      molecules, the results are analyzed statistically and problematic cases have been
      discussed in detail. It is concluded that the mean deviation of the CC2 results
      is smaller than that of the CCSD. However, the latter seems to be more
      systematic, i.e. it usually overestimates excitation energies by about 0.2 eV but
      with somewhat smaller standard deviation. Unfortunately, with decreasing single
      excitation contribution in the wave function CCSD gives large error, which can
      not be corrected by the non-iterative triples methods CCSDR(3) and EOM-CCSD(T). 

PMID- 25394401
TI  - Discovery of novel covalent proteasome inhibitors through a combination of
      pharmacophore screening, covalent docking, and molecular dynamics simulations.
AB  - The ubiquitin-proteasome pathway plays a pivotal role in the regulation of
      cellular protein processing and degradation. Proteasome inhibitors (PIs) have
      enormous potential to treat multiple myeloma, solid tumors, parasites,
      inflammation, and immune diseases, which is spurring the development of new types
      of PIs with enhanced efficacy, fewer side effects, and reduced drug resistance.
      Nevertheless, virtual screening for covalent PIs has rarely been reported because
      calculating the covalent binding energy is a challenging task. The aim of this
      study was to discover new covalent inhibitors of the 20S proteasome. The
      structures of PIs were manually divided into two parts: a noncovalent binding
      part resulting from virtual screening, and an epoxyketone group that was pre
      selected as a covalent binding part. The SPECS database was screened by
      noncovalent docking and a pharmacophore model built with the 20S proteasome.
      After validating the covalent conjugation, 88 hits with epoxyketone were
      covalently docked into the 20S proteasome to analyze the intermolecular
      interactions. Four compounds were selected after multiple filtration and
      validations. Molecular dynamics simulations were performed to check the stability
      of the noncovalent and covalent docked ligand-enzyme complexes and investigate
      the interaction patterns of the screened inhibitors. Finally, two compounds with
      novel aromatic backbones, reasonable interactions, and stable covalent binding
      modes were retained. These compounds can serve as potential hits for further
      biological evaluation. 

PMID- 25394402
TI  - A case of pulmonary hamartoma with distinctive histopathological features: a
      discussion of its differential diagnosis and histogenesis.
AB  - We herein describe a case of a benign pulmonary tumor with distinctive
      histopathological features. A 55-year-old Japanese male presented with a well
      demarcated tumor in the left upper lobe of his lung, which gradually increased in
      size from 18 to 21 mm over 24 months. The resected tumor consisted of an
      epithelial component of compact irregular glands and mesenchymal component of
      fascicles between the glands. The differentiation of pneumocytes and smooth
      muscle cells was immunohistochemically detected in the epithelial component and
      the mesenchymal component, respectively. No mitosis, necrosis, bleeding, or
      invasion was observed. A histopathologic diagnosis of fibroleiomyomatous
      hamartoma was made. We also review previously reported tumors with similar
      histopathological features and discuss their differential diagnosis and
      histogenesis. 

PMID- 25394403
TI  - Mood, anxiety and psychotic phenomena measure a common psychopathological factor.
AB  - BACKGROUND: Psychotic phenomena are common in the general population but are
      excluded from diagnostic criteria for mild to moderate depression and anxiety
      despite their co-occurrence and shared risk factors. We used item response theory
      modelling to examine whether the co-occurrence of depressive, anxiety and
      psychotic phenomena is best explained by: (1) a single underlying factor; (2) two
      separate, uncorrelated factors; (3) two separate yet linked factors; or (4) two
      separate domains along with an underlying 'common mental distress' (CMD) factor.
      We defined where, along any latent continuum, the psychopathological items
      contributed most information. METHOD: We performed a secondary analysis of cross
      sectional, item-level information from measures of depression, anxiety and
      psychotic experiences in 6617 participants aged 13 years from the Avon
      Longitudinal Study of Parents and Children (ALSPAC) birth cohort and 977
      participants aged 18 years from the ROOTS schools-based sample. We replicated
      results from one sample in the other and validated the latent factors against an
      earlier parental measure of mental state. RESULTS: In both cohorts depression,
      anxiety and psychotic items were best represented as a bi-factor model with a
      single, unitary CMD factor on which psychotic items conveyed information about
      the more severe end (model 4); residual variation remained for psychotic items.
      The CMD factor was significantly associated with the prior parental measure.
      CONCLUSIONS: Psychotic phenomena co-occur with depression and anxiety in
      teenagers and may be a marker of severity in a single, unitary dimension of CMD.
      Psychotic phenomena should be routinely included in epidemiological assessments
      of psychiatric morbidity, otherwise the most severe symptomatology remains
      unmeasured.

PMID- 25394404
TI  - Level of nutrition knowledge and its association with weight loss behaviors among
      low-income reproductive-age women.
AB  - To examine influence of nutrition knowledge on weight loss behaviors among low
      income reproductive-age women. We conducted a self-administered cross-sectional
      survey of health behaviors including socio-demographic characteristics, nutrition
      knowledge, and weight loss behaviors of 16-40 year old women (n = 1,057)
      attending reproductive health clinics located in Southeast Texas between July
      2010 and February 2011. Multiple linear regression and multivariable logistic
      regression analyses were performed to identify correlates of nutrition knowledge
      and examine its association with various weight loss behaviors after adjusting
      for confounders. The mean nutrition knowledge score was low (5.7 +/- 2.8)
      (possible score 0-15). It was significantly lower among African American women
      than whites (P < .001). Obese women (P = .002), women with high school
      enrollment/diploma (P = .030), and some college hours/degree (P < .001) had
      higher nutrition knowledge scores than their counterparts. The higher score of
      nutrition knowledge was significantly associated with higher odds of engaging in
      healthy weight loss behaviors: eating less food [odds ratio (OR) 1.12, 95%
      confidence interval (CI) 1.06-1.18], switching to foods with fewer calories (OR
      1.10, 95% CI 1.04-1.16), exercising (OR 1.10, 95% CI 1.04-1.16), eating more
      fruits/vegetables/salads (OR 1.11, 95% CI 1.06-1.17) and less sugar/candy/sweets
      (OR 1.09, 95% CI 1.04-1.15). However, it was not associated with unhealthy weight
      loss behaviors, such as using laxatives/diuretics or inducing vomiting. Nutrition
      knowledge is low among reproductive-age women. An increase in nutrition knowledge
      may promote healthy weight loss behaviors.

PMID- 25394405
TI  - Pathophysiology, diagnosis and treatment of varicoceles: a review.
AB  - In this article we reviewed the pathophysiology, diagnosis and treatment of
      varicoceles. The etiology and pathogenesis of varicoceles cannot be explained by
      one theory. Valve dysfunction, ontogenetic collateral formation and the
      nutcracker phenomenon seem to act synergistically. Hyperthermia, elevated
      hydrostatic pressure and antisperm agents are suggested as possible causes for
      the pathophysiology how varicoceles induce infertility. However the combination
      of patient's lifestyle, genetic factors and the consequences of reflux into the
      pampiniform plexus are believed to contribute to the infertility. Although
      venography stays the gold standard, the combination of physical examination,
      color Doppler ultrasound and thermography has the highest sensitivity and
      specificity to diagnose a varicocele. Regarding infertility, we are still
      searching for strict criteria or grading, to decide which patients with a
      varicocele may or may not have benefit from treatment. Treatment of varicoceles
      can be performed by different open surgical or percutaneous techniques. Treatment
      of varicoceles for infertility or to prevent infertility remains controversial,
      because the majority of men with varicoceles are still fertile. At the moment,
      inguinal or subinguinal microscopic surgery gave the highest pregnancy rates, the
      lowest recurrence and lowest complication rates. But retrograde superselective
      glue embolization or sclerosing of the ISV are the best percutaneous alternative
      and can be performed on an outpatient basis under local anesthesia and with
      faster return to normal activities than surgery. 

PMID- 25394406
TI  - Microbial electricity generation in rice paddy fields: recent advances and
      perspectives in rhizosphere microbial fuel cells.
AB  - Microbial fuel cells (MFCs) are devices that use living microbes for the
      conversion of organic matter into electricity. MFC systems can be applied to the
      generation of electricity at water/sediment interfaces in the environment, such
      as bay areas, wetlands, and rice paddy fields. Using these systems, electricity
      generation in paddy fields as high as ~80 mW m(-2) (based on the projected anode
      area) has been demonstrated, and evidence suggests that rhizosphere microbes
      preferentially utilize organic exudates from rice roots for generating
      electricity. Phylogenetic and metagenomic analyses have been conducted to
      identify the microbial species and catabolic pathways that are involved in the
      conversion of root exudates into electricity, suggesting the importance of
      syntrophic interactions. In parallel, pot cultures of rice and other aquatic
      plants have been used for rhizosphere MFC experiments under controlled laboratory
      conditions. The findings from these studies have demonstrated the potential of
      electricity generation for mitigating methane emission from the rhizosphere.
      Notably, however, the presence of large amounts of organics in the rhizosphere
      drastically reduces the effect of electricity generation on methane production.
      Further studies are necessary to evaluate the potential of these systems for
      mitigating methane emission from rice paddy fields. We suggest that paddy-field
      MFCs represent a promising approach for harvesting latent energy of the natural
      world.

PMID- 25394407
TI  - Arthrodesis of the proximal interphalangeal joints of a hindlimb in a heifer.
AB  - A two-year-old Braunvieh heifer was presented with a traumatic luxation of the
      second phalanx of the medial digit and concurrent subluxation of the second
      phalanx of the lateral digit of the right hindlimb. Closed reduction of both
      luxations was possible. Surgical arthrodesis was achieved using one narrow 4.5 mm
      three-hole equine locking compression plate for each joint. Placement of the bone
      plates resulted in stable arthrodesis of both proximal interphalangeal joints of
      the right hindlimb but there was persistent residual lameness. The heifer
      delivered a healthy calf but was slaughtered eight months after surgery because
      of varus deformity of the contralateral limb. Radiographs taken post-mortem
      revealed pronounced periosteal reactions involving both proximal interphalangeal
      joints and only partial bony bridging of the joint spaces. 

PMID- 25394408
TI  - Establishment of human pancreatic cancer gemcitabine-resistant cell line with
      ribonucleotide reductase overexpression.
AB  - A gemcitabine (GEM)-resistant human pancreatic cancer cell line (PANC-1RG7) was
      established in vitro by gradually increasing GEM concentrations and cloning cell
      cultures to develop a cellular model of acquired drug resistance studies. We
      found that PANC-1RG7 cells exhibited significantly different morphological
      characteristics from parental cells. PANC-1RG7 cells grew slowly (p<0.05), yet
      the cell cycle remained unchanged (p>0.05). PANC-1RG7, with a resistance index to
      GEM of 39.9, showed cross-resistance characteristics to methotrexate, gefitinib,
      cisplatin and 5-fluorouracil. The proliferation inhibition of GEM was
      significantly reduced in vivo (p<0.05). The known resistance-associated genes and
      proteins we detected remained unchanged, with the exception of cytidine
      deaminase, multidrug resistance-related protein and breast cancer resistance
      protein genes, which decreased; by contrast, 5'-nucleotidase, ribonucleotide
      reductase (RRM) 1 and RRM2 proteins increased (p<0.05). Therefore, a cell line
      with acquired GEM resistance was established successfully. Resistance was
      acquired by overexpressing RRM1 and RRM2 proteins.

PMID- 25394409
TI  - Inverse correlation between Alzheimer's disease and cancer: implication for a
      strong impact of regenerative propensity on neurodegeneration?
AB  - BACKGROUND: Recent studies have revealed an inverse epidemiological correlation
      between Alzheimer's disease (AD) and cancer - patients with AD show a reduced
      risk of cancer, while cancer survivors are less likely to develop AD. These late
      discoveries in human subjects call for explorative studies to unlock the
      underlying biological mechanism, but also may shed new light on conceptual
      interrogation of the principal pathogenic players in AD etiology. DISCUSSION:
      Here we hypothesize that this negative correlation reflects a rebalance of
      biosynthetic propensity between body systems under the two disease statuses. In
      normal condition the body cellular systems are maintained homeostatically under a
      balanced cell degenerative vs. surviving/regenerative propensities, determined by
      biosynthetic resources for anabolic processing. AD pathogenesis involves
      neurodegeneration but also aberrant regenerative, or reactive anabolic, burden,
      while cancer development is driving by uncontrolled proliferation inherent with
      excessive anabolic activity. The aberrant neural regenerative propensity in AD
      pathogenesis and the uncontrolled cellular proliferative propensity in cancer
      pathogeneses can manifest as competitive processes, which could result in the
      inverse epidemiological correlation seen among the elderly. SUMMARY: The reduced
      prevalence of AD in cancer survivors may implicate a strong impact of aberrant
      neural regenerative burden in neurodegeneration. Further explorative studies into
      the inverse correlation between AD and cancer should include examinations of the
      proliferative propensity of tumor cells in AD models, and the development of AD
      like neuropathology in cancer models as well as following anti-proliferative drug
      treatment.

PMID- 25394410
TI  - Fabrication of thickness controllable free-standing sandwich-structured hybrid
      carbon film for high-rate and high-power supercapacitor.
AB  - Hybrid carbon films composed of graphene film and porous carbon film may give
      full play to the advantages of both carbon materials, and have great potential
      for application in energy storage and conversion devices. Unfortunately, there
      are very few reports on fabrication of hybrid carbon films. Here we demonstrate a
      simple approach to fabricate free-standing sandwich-structured hybrid carbon film
      composed of porous amorphous carbon film and multilayer graphene film by chemical
      vapor deposition in a controllable and scalable way. Hybrid carbon films reveal
      good electrical conductivity, excellent flexibility, and good compatibility with
      substrate. Supercapacitors assembled by hybrid carbon films exhibit ultrahigh
      rate capability, wide frequency range, good capacitance performance, and high
      power density. Moreover, this approach may provide a general path for fabrication
      of hybrid carbon materials with different structures by using different metals
      with high carbon solubility, and greatly expands the application scope of carbon
      materials. 

PMID- 25394411
TI  - Correction.
AB  - [This corrects the article DOI: 10.1136/lupus-2014-000048.]. 

PMID- 25394413
TI  - Omentin-1 promotes the growth of neural stem cells via activation of Akt
      signaling.
AB  - Omentin is a novel adipokine, which is expressed in and released from omental
      adipose tissue. In the present study, the effect of omentin on neural stem cells
      (NSCs) was investigated. NSCs are a subtype of stem cell in the nervous system,
      which are able to self-renew and generate neurons and glia for repairing neural
      lesions. Mouse NSCs were isolated and cultured in vitro. Treatment with
      recombinant omentin for 3 and 5 days significantly increased the size of NSC
      neurospheres (P<0.01) and enhanced NSC cell viability in normal conditions. In
      addition, omentin protected against the decrease in cell viability induced by the
      pro-inflammatory cytokine tumor necrosis factor-alpha. In the NSCs, incubation of
      omentin for 2, 4, 6, 8 and 16 h enhanced the phosphorylation of Akt at the Thr308
      site and of AS160 at the Ser318 site, peaking 6 h after treatment. Additionally,
      treatment with LY294002 (10 uM), a specific inhibitor of phosphatidylinositol 3
      kinase/Akt signaling, eliminated the omentin-induced increase in neurosphere size
      and cell viability. Overall, the present study provided the first evidence, to
      the best of our knowledge, that omentin promotes the growth and survival of NSCs
      in vitro through activation of the Akt signaling pathway. These results may
      contribute to the understanding of the role of omentin in the nervous system.

PMID- 25394414
TI  - AACE safety alert--glucose monitoring systems AACE-.

PMID- 25394412
TI  - Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of
      mouse mammary tumor virus (MMTV).
AB  - BACKGROUND: One of the hallmarks of retroviral life cycle is the efficient and
      specific packaging of two copies of retroviral gRNA in the form of a non-covalent
      RNA dimer by the assembling virions. It is becoming increasingly clear that the
      process of dimerization is closely linked with gRNA packaging, and in some
      retroviruses, the latter depends on the former. Earlier mutational analysis of
      the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants
      comprise sequences both within the 5' untranslated region (5' UTR) and the
      beginning of gag. RESULTS: The RNA secondary structure of MMTV gRNA packaging
      sequences was elucidated employing selective 2'hydroxyl acylation analyzed by
      primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long
      range interaction (U5/Gag LRI), not predicted by minimum free-energy structure
      predictions that potentially stabilizes the global structure of this region.
      Structure conservation along with base-pair covariations between different
      strains of MMTV further supported the SHAPE-validated model. The 5' region of the
      MMTV gRNA contains multiple palindromic (pal) sequences that could initiate
      intermolecular interaction during RNA dimerization. In vitro RNA dimerization,
      SHAPE analysis, and structure prediction approaches on a series of pal mutants
      revealed that MMTV RNA utilizes a palindromic point of contact to initiate
      intermolecular interactions between two gRNAs, leading to dimerization. This
      contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a
      canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization
      initiation site (DIS). Further analyses of these pal mutants employing in vivo
      genetic approaches indicate that pal II, as well as pal sequences located in the
      primer binding site (PBS) are both required for efficient MMTV gRNA packaging.
      CONCLUSIONS: Employing structural prediction, biochemical, and genetic
      approaches, we show that pal II functions as a primary point of contact between
      two MMTV RNAs, leading to gRNA dimerization and its subsequent encapsidation into
      the assembling virus particles. The results presented here enhance our
      understanding of the MMTV gRNA dimerization and packaging processes and the role
      of structural motifs with respect to RNA-RNA and possibly RNA-protein
      interactions that might be taking place during MMTV life cycle.

PMID- 25394415
TI  - Decreased tumorigenesis in mice with a Kras point mutation at C118.
AB  - KRAS, NRAS or HRAS genes are mutated to encode an active oncogenic protein in a
      quarter of human cancers. Redox-dependent reactions can also lead to Ras
      activation in a manner dependent upon the thiol residue of cysteine 118 (C118).
      Here, to investigate the effect of mutating this residue on tumorigenesis, we
      introduce a C118S mutation into the endogenous murine Kras allele and expose the
      resultant mice to the carcinogen urethane, which induces Kras mutation-positive
      lung tumours. We report that Kras(+/C118S) and Kras(C118S/C118S) mice develop
      fewer lung tumours. Although the Kras(C118S) allele does not appear to affect
      tumorigenesis when the remaining Kras allele is conditionally oncogenic, there is
      a moderate imbalance of oncogenic mutations favouring the native Kras allele in
      tumours from Kras(+/C118S) mice treated with urethane. We conclude that the
      Kras(C118S) allele impedes urethane-induced lung tumorigenesis. 

PMID- 25394416
TI  - Elastic properties of the young aorta: ex vivo perfusion experiments in a porcine
      model.
AB  - OBJECTIVES: To investigate the regional and directional compliance/distensibility
      of the healthy aorta. METHODS: Complete fresh porcine aortas (n = 11) were
      perfused ex vivo under defined haemodynamic parameters using a custom-made pulse
      duplicator. Both circumferential and longitudinal compliance were measured
      optically. RESULTS: The pulse duplicator was able to perfuse the entire aorta
      with arbitrary haemodynamic parameters, generating a physiological pulse curve.
      Aortic compliance is pressure dependent, as we observed a linear relationship
      between pressure and distension in the range of 5-200 mmHg; however, above 200
      mmHg, the porcine aorta behaved in an inelastic manner. Circumferential
      compliance was highest in the ascending aorta (24%/100 mmHg) but significantly (P
      < 0.05) decreased in both the arch (18%/100 mmHg) and the descending aorta
      (15%/100 mmHg). Longitudinal compliance was highest in the ascending aorta and
      clearly exceeded circumferential compliance. Compliance was significantly (P <
      0.05) higher in the outer curvatures of the ascending aorta and the aortic arch
      compared with the compliance of the inner curvature at these locations (30%/100
      vs 23%/100 mmHg in the ascending aorta and 20%/100 vs 9%/100 mmHg in the arch,
      respectively). CONCLUSIONS: Longitudinal compliance of the ascending aorta,
      particularly the outer curvature, is predominantly responsible for the
      'Windkessel effect'. Pathological changes such as elongation and pronounced
      angulation of the ascending aorta increase stress on the outer curvature and may
      be important factors in the development of aortic dissection.

PMID- 25394417
TI  - Bilateral pulmonary sequestration with mixed infection caused by two types of non
      tuberculous mycobacteria in pregnancy.

PMID- 25394418
TI  - Identification of six New World Leishmania species through the implementation of
      a High-Resolution Melting (HRM) genotyping assay.
AB  - BACKGROUND: Leishmaniases are tropical zoonotic diseases, caused by parasites
      from the genus Leishmania. New World (NW) species are related to sylvatic cycles
      although urbanization processes have been reported in some South American
      Countries such as Colombia. This eco-epidemiological complexity imposes a
      challenge to the detection of circulating parasite species, not only related to
      human cases but also infecting vectors and reservoirs. Currently, no harmonized
      methods have been deployed to discriminate the NW Leishmania species. FINDINGS:
      Herein, we conducted a systematic and mechanistic High-Resolution Melting (HRM)
      assay targeted to HSP70 and ITS1. Specific primers were designed that coupled
      with a HRM analyses permitted to discriminate six NW Leishmania species. In order
      to validate the herein described algorithm, we included 35 natural isolates
      obtained from human cases, insect vectors and mammals. Our genotyping assay
      allowed the correct assignment of the six NW Leishmania species (L. mexicana, L.
      infantum (chagasi), L. amazonensis, L. panamensis, L. guyanensis and L.
      braziliensis) based on reference strains. When the algorithm was applied to a set
      of well-characterized strains by means of PCR-RFLP, MLEE and monoclonal
      antibodies (MA) we observed a tailored concordance between the HRM and PCR
      RFLP/MLEE/MA (KI = 1.0). Additionally, we tested the limit of detection for the
      HRM method showing that this is able to detect at least 10 equivalent-parasites
      per mL. CONCLUSIONS: This is a rapid and reliable method to conduct molecular
      epidemiology and host-parasite association studies in endemic areas.

PMID- 25394419
TI  - Parietal neural prosthetic control of a computer cursor in a graphical-user
      interface task.
AB  - OBJECTIVE: To date, the majority of Brain-Machine Interfaces have been used to
      perform simple tasks with sequences of individual targets in otherwise blank
      environments. In this study we developed a more practical and clinically relevant
      task that approximated modern computers and graphical user interfaces (GUIs).
      This task could be problematic given the known sensitivity of areas typically
      used for BMIs to visual stimuli, eye movements, decision-making, and attentional
      control. Consequently, we sought to assess the effect of a complex, GUI-like task
      on the quality of neural decoding. APPROACH: A male rhesus macaque monkey was
      implanted with two 96-channel electrode arrays in area 5d of the superior
      parietal lobule. The animal was trained to perform a GUI-like 'Face in a Crowd'
      task on a computer screen that required selecting one cued, icon-like, face image
      from a group of alternatives (the 'Crowd') using a neurally controlled cursor. We
      assessed whether the crowd affected decodes of intended cursor movements by
      comparing it to a 'Crowd Off' condition in which only the matching target
      appeared without alternatives. We also examined if training a neural decoder with
      the Crowd On rather than Off had any effect on subsequent decode quality. MAIN
      RESULTS: Despite the additional demands of working with the Crowd On, the animal
      was able to robustly perform the task under Brain Control. The presence of the
      crowd did not itself affect decode quality. Training the decoder with the Crowd
      On relative to Off had no negative influence on subsequent decoding performance.
      Additionally, the subject was able to gaze around freely without influencing
      cursor position. SIGNIFICANCE: Our results demonstrate that area 5d recordings
      can be used for decoding in a complex, GUI-like task with free gaze. Thus, this
      area is a promising source of signals for neural prosthetics that utilize
      computing devices with GUI interfaces, e.g. personal computers, mobile devices,
      and tablet computers.

PMID- 25394420
TI  - Classification and grading of muscle injuries: a narrative review.
AB  - A limitation to the accurate study of muscle injuries and their management has
      been the lack of a uniform approach to the categorisation and grading of muscle
      injuries. The goal of this narrative review was to provide a framework from which
      to understand the historical progression of the classification and grading of
      muscle injuries. We reviewed the classification and grading of muscle injuries in
      the literature to critically illustrate the strengths, weaknesses, contradictions
      or controversies. A retrospective, citation-based methodology was applied to
      search for English language literature which evaluated or utilised a novel muscle
      classification or grading system. While there is an abundance of literature
      classifying and grading muscle injuries, it is predominantly expert opinion, and
      there remains little evidence relating any of the clinical or radiological
      features to an established pathology or clinical outcome. While the categorical
      grading of injury severity may have been a reasonable solution to a clinical
      challenge identified in the middle of the 20th century, it is time to recognise
      the complexity of the injury, cease trying to oversimplify it and to develop
      appropriately powered research projects to answer important questions. 

PMID- 25394421
TI  - Cardiovascular evaluation of middle-aged individuals engaged in high-intensity
      sport activities: implications for workload, yield and economic costs.
AB  - BACKGROUND: The European Association of Cardiovascular Prevention and
      Rehabilitation (EACPR) recommends cardiovascular evaluation of middle-aged
      individuals engaged in sport activities. However, very few data exist concerning
      the impact of such position stand. We assessed the implications on workload,
      yield and economic costs of this preventive strategy. METHODS: Individuals aged
      35-65 years engaged in high-intensity sports were examined following the EACPR
      protocol. Athletes with abnormal findings or considered at high-cardiovascular
      risk underwent additional examinations. The costs of the overall evaluation until
      diagnosis were calculated according to Swiss medical rates. RESULTS: 785 athletes
      (73% males, 46.8+/-7.3 years) were enrolled over a 13-month period. Among them,
      14.3% required additional examinations: 5.1% because of abnormal ECG, 4.7% due to
      physical examination, 4.1% because of high-cardiovascular risk and 1.6% due to
      medical history. A new cardiovascular abnormality was established in 2.8% of
      athletes, severe hypercholesterolaemia in 1% and type 2 diabetes in 0.1%. Three
      (0.4%) athletes were considered ineligible for high-intensity sports, all of them
      discovered through an abnormal ECG. No athlete was diagnosed with significant
      coronary artery disease on the basis of a high-risk profile or an exercise ECG.
      The cost was US$199 per athlete and US$5052 per new finding. CONCLUSIONS:
      Cardiovascular evaluation of middle-aged athletes detected a new cardiovascular
      abnormality in about 3% of participants and a high-cardiovascular risk profile in
      about 4%. Some of these warranted exclusion of the athlete from high-intensity
      sport. The overall evaluation seems to be feasible at reasonable costs.

PMID- 25394422
TI  - Plantaris excision in the treatment of non-insertional Achilles tendinopathy in
      elite athletes.
AB  - BACKGROUND: Achilles tendinopathy is a serious and frequently occurring problem,
      especially in elite athletes. Recent research has suggested a role for the
      plantaris tendon in non-insertional Achilles tendinopathy. AIM: To assess whether
      excising the plantaris tendon improved the symptoms of Achilles tendinopathy in
      elite athletes. METHODS: This prospective consecutive case series study
      investigated 32 elite athletes who underwent plantaris tendon excision using a
      mini-incision technique to treat medially located pain associated with non
      insertional Achilles tendinopathy. Preoperative and postoperative visual analogue
      scores (VAS) for pain and the foot and ankle outcome score (FAOS) as well as time
      to return to sport and satisfaction scores were assessed. RESULTS: At a mean
      follow-up of 22.4 months (12-48), 29/32 (90%) of athletes were satisfied with the
      results. Thirty of the 32 athletes (94%) returned to sport at a mean of 10.3
      weeks (5-27). The mean VAS score improved from 5.8 to 0.8 (p<0.01) and the mean
      FAOS improved in all domains (p<0.01). Few complications were seen, four athletes
      experienced short-term stiffness and one had a superficial wound infection.
      CONCLUSIONS: The plantaris tendon may be responsible for symptoms in some
      athletes with non-insertional Achilles tendinopathy. Excision carries a low risk
      of complications and may provide significant improvement in symptoms enabling an
      early return to elite-level sports.

PMID- 25394424
TI  - Diverse melting modes and structural collapse of hollow bimetallic core-shell
      nanoparticles: a perspective from molecular dynamics simulations.
AB  - Introducing hollow structures into metallic nanoparticles has become a promising
      route to improve their catalytic performances. A fundamental understanding of
      thermal stability of these novel nanostructures is of significance for their
      syntheses and applications. In this article, molecular dynamics simulations have
      been employed to offer insights into the thermodynamic evolution of hollow
      bimetallic core-shell nanoparticles. Our investigation reveals that for hollow Pt
      core/Au-shell nanoparticle, premelting originates at the exterior surface, and a
      typical two-stage melting behavior is exhibited, similar to the solid ones.
      However, since the interior surface provides facilitation for the premelting
      initiating at the core, the two-stage melting is also observed in hollow Au
      core/Pt-shell nanoparticle, remarkably different from the solid one. Furthermore,
      the collapse of hollow structure is accompanied with the overall melting of the
      hollow Pt-core/Au-shell nanoparticle while it occurs prior to that of the hollow
      Au-core/Pt-shell nanoparticle and leads to the formation of a liquid-core/solid
      shell structure, although both of them finally transform into a mixing alloy with
      Au-dominated surface. Additionally, the existence of stacking faults in the
      hollow Pt-core/Au-shell nanoparticle distinctly lowers its melting point. This
      study could be of great importance to the design and development of novel
      nanocatalysts with both high activity and excellent stability. 

PMID- 25394423
TI  - Pulmonary and hemostatic toxicity of multi-walled carbon nanotubes and zinc oxide
      nanoparticles after pulmonary exposure in Bmal1 knockout mice.
AB  - BACKGROUND: Pulmonary exposure to nanoparticles (NPs) may affect, in addition to
      pulmonary toxicity, the cardiovascular system such as procoagulant effects,
      vascular dysfunction and progression of atherosclerosis. However, only few
      studies have investigated hemostatic effects after pulmonary exposure. METHODS:
      We used Bmal1 (brain and muscle ARNT-like protein-1) knockout (Bmal1(-/-)) mice
      which have a disturbed circadian rhythm and procoagulant phenotype, to study the
      pulmonary and hemostatic toxicity of multi-walled carbon nanotubes (MWCNTs) and
      zinc oxide (ZnO) NPs after subacute pulmonary exposure. Bmal1(-/-) and wild-type
      (Bmal1(+/+)) mice were exposed via oropharyngeal aspiration, once a week, during
      5 consecutive weeks, to a cumulative dose of 32 or 128 MUg MWCNTs or 32 or 64 MUg
      ZnO NPs. RESULTS: MWCNTs caused a pronounced inflammatory response in the lung
      with increased cell counts in the broncho-alveolar lavage and increased secretion
      of interleukin-1beta and cytokine-induced neutrophil chemo-attractant (KC),
      oxidative stress (increased ratio of oxidized versus reduced glutathione and
      decreased total glutathione) as well as anemic and procoagulant effects as
      evidenced by a decreased prothrombin time with increased fibrinogen
      concentrations and coagulation factor (F)VII. In contrast, the ZnO NPs seemed to
      suppress the inflammatory (decreased neutrophils in Bmal1(-/-) mice) and
      oxidative response (increased total glutathione in Bmal1(-/-) mice), but were
      also procoagulant with a significant increase of FVIII. The procoagulant effects,
      as well as the significant correlations between the pulmonary endpoints
      (inflammation and oxidative stress) and hemostasis parameters were more
      pronounced in Bmal1(-/-) mice than in Bmal1(+/+) mice. CONCLUSIONS: The Bmal1(-/
      ) mouse is a sensitive animal model to study the procoagulant effects of
      engineered NPs. The MWCNTs and ZnO NPs showed different pulmonary toxicity but
      both NPs induced procoagulant effects, suggesting different mechanisms of
      affecting hemostasis. However, the correlation analysis suggests a causal
      association between the observed pulmonary and procoagulant effects.

PMID- 25394425
TI  - Effectiveness of passive physical modalities for shoulder pain: systematic review
      by the Ontario protocol for traffic injury management collaboration.
AB  - BACKGROUND: Shoulder pain is a common musculoskeletal condition in the general
      population. Passive physical modalities are commonly used to treat shoulder pain.
      However, previous systematic reviews reported conflicting results. PURPOSE: The
      aim of this study was to evaluate the effectiveness of passive physical
      modalities for the management of soft tissue injuries of the shoulder. DATA
      SOURCES: MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of
      Controlled Trials were searched from January 1, 1990, to April 18, 2013. STUDY
      SELECTION: Randomized controlled trials (RCTs) and cohort and case-control
      studies were eligible. Random pairs of independent reviewers screened 1,470 of
      1,760 retrieved articles after removing 290 duplicates. Twenty-two articles were
      eligible for critical appraisal. Eligible studies were critically appraised using
      the Scottish Intercollegiate Guidelines Network criteria. Of those, 11 studies
      had a low risk of bias. DATA EXTRACTION: The lead author extracted data from low
      risk of bias studies and built evidence tables. A second reviewer independently
      checked the extracted data. DATA SYNTHESIS: The findings of studies with a low
      risk of bias were synthesized according to principles of best evidence synthesis.
      Pretensioned tape, ultrasound, and interferential current were found to be
      noneffective for managing shoulder pain. However, diathermy and corticosteroid
      injections led to similar outcomes. Low-level laser therapy provided short-term
      pain reduction for subacromial impingement syndrome. Extracorporeal shock-wave
      therapy was not effective for subacromial impingement syndrome but provided
      benefits for persistent shoulder calcific tendinitis. LIMITATIONS: Non-English
      studies were excluded. CONCLUSIONS: Most passive physical modalities do not
      benefit patients with subacromial impingement syndrome. However, low-level laser
      therapy is more effective than placebo or ultrasound for subacromial impingement
      syndrome. Similarly, shock-wave therapy is more effective than sham therapy for
      persistent shoulder calcific tendinitis.

PMID- 25394426
TI  - Erratum: EMSAM (deprenyl patch): how a promising antidepressant was underutilized
      [Corrigendum].
AB  - [This corrects the article on p. 1911 in vol. 10, PMID: 25336957.]. 

PMID- 25394428
TI  - Assessment of allograft function using diffusion-weighted magnetic resonance
      imaging in kidney transplant patients.
AB  - Developing a non-invasive method such as diffusion-weighted magnetic resonance
      imaging (DWMRI) could be used as a feasible and reproducible modality in the
      differential diagnosis of allograft dysfunction. We assessed the functional
      status of the renal allograft by DWMRI and its applicability in assessment of
      graft dysfunction on all end-stage renal transplant patients who attained normal
      renal function on the 7th day post-transplantation. Follow-up imaging of the
      recipient allograft was performed at the end of 90 and 180 days and in case of
      graft dysfunction. Kidney biopsies were performed to correlate with the
      corresponding MRI. The apparent diffusion coefficient (ADC) maps of the cortex
      and medulla were obtained by studying the DWMRI. The ADC values were
      significantly lower in the medulla compared with the cortex in normal donor
      kidneys and normally functioning transplanted kidneys, while they decreased
      significantly when rejection occurred. The reduction in ADC values occurred both
      in the cortex and in the medulla, and correlated with the degree of rejection on
      the kidney biopsies. The ADC values increased significantly during the recovery
      from rejection. We conclude that DWMRI can be beneficial in the diagnosis and
      follow-up of transplant patients during acute rejection.

PMID- 25394427
TI  - Codon optimization and factorial screening for enhanced soluble expression of
      human ciliary neurotrophic factor in Escherichia coli.
AB  - BACKGROUND: Neurotrophic factors influence survival, differentiation,
      proliferation and death of neuronal cells within the central nervous system.
      Human ciliary neurotrophic factor (hCNTF) has neuroprotective properties and is
      also known to influence energy balance. Consequently, hCNTF has potential
      therapeutic applications in neurodegenerative, obesity and diabetes related
      disorders. Clinical and biological applications of hCNTF necessitate a
      recombinant expression system to produce large amounts of functional protein in
      soluble form. Earlier attempts to express hCNTF in Escherichia coli (E. coli)
      were limited by low amounts and the need to refold from inclusion bodies.
      RESULTS: In this report, we describe a strategy to effectively identify
      constructs and conditions for soluble expression of hCNTF in E. coli. Small-scale
      expression screening with soluble fusion tags identified many conditions that
      yielded soluble expression. Codon optimized 6-His-hCNTF construct showed soluble
      expression in all the conditions tested. Large-scale culture of the 6-His-hCNTF
      construct yielded high (10 - 20 fold) soluble expression (8 - 9 fold) as compared
      to earlier published reports. Functional activity of recombinant 6-His-hCNTF
      produced was confirmed by its binding to hCNTF receptor (hCNTFRalpha) with an
      EC50 = 36 nM. CONCLUSION: Our results highlight the combination of codon
      optimization and screening soluble fusion tags as a successful strategy for high
      yielding soluble expression of hCNTF in E. coli. Codon optimization of the hCNTF
      sequence seems to be sufficient for soluble expression of hCNTF. The combined
      approach of codon optimization and soluble fusion tag screen can be an effective
      strategy for soluble expression of pharmaceutical proteins in E. coli.

PMID- 25394429
TI  - Effect of intraoperative human albumin on early graft function in renal
      transplantation.
AB  - Adequate intravascular volume maintenance is essential to ensure early graft
      function during renal transplantation. Various recommendations on optimum fluid
      therapy are based, at best, on sparse evidence, and that too only from
      observational studies. This prospective randomized controlled study was done to
      evaluate the effect of 20% human albumin on the early graft function in living
      donor renal transplantation. Eighty patients undergoing renal transplantation
      were randomly assigned to one of the intraoperative fluid regimens, 0.9% normal
      saline with 20% human albumin (albumin group) or 0.9% normal saline alone (saline
      group), after confirming the exclusion criteria. Intravenous fluid infusion was
      given to keep central venous pressure (CVP) between 12 to 15 mm Hg. The
      statistical package of social sciences, SPSS version 12, was used for statistical
      analysis. The intraoperative fluid volume infused [albumin group--3381+/-1021.2
      vs. saline group--3487+/-978.5 (mL)] to maintain target CVP was comparable
      between the two groups (P value>0.05). Statistically, no significant difference
      was found between the two groups in terms of post transplant serum creatinine
      [day one; 2.76+/-1.0 vs. 2.58+/-0.94, day three; 1.48+/-0.53 vs. 1.43+/-0.71, day
      seven; 1.42+/-0.6 vs. 1.42+/-0.53 (mg/dL)] and urine output [day one; 13122.5+/
      5767.8 vs. 13909.4+/-5324.7, day three; 9233.9+/-3267.4 vs. 9250+/-4794.2, day
      seven; 7517.6+/-3043.6 vs. 6921.4+/-3170 (mL)] (P value>0.05). Postoperative
      change in body weight [1.89+/-3.82 vs. 2.48+/-3.89 (kg)], tissue edema (10% vs.
      7.5%), and pulmonary edema (2.5% vs. 5%) did not differ significantly (P>0.05).
      Twenty percent human albumin given intraoperatively, as a volume expander, does
      not improve early graft function in living donor renal transplantation. It should
      be used selectively rather than as a routine protocol.

PMID- 25394430
TI  - The effect of mannitol administration to kidney donor on short-term outcomes of
      kidney transplantation.
AB  - As the cases of kidney transplant are increasing, the need to apply the factors
      to increase the success of transplant seems necessary. Mannitol increases the
      osmotic pressure and urine volume as a protective agent on renal tubules. We
      aimed to evaluate the effect of mannitol on short-term outcome of kidney
      transplantation by comparing two groups based on prescribing mannitol to donors.
      In a randomized clinical trial, 60 kidney recipients were assigned in two groups
      (30 in each), except that in one group donors received mannitol. They were
      studied with respect to age, gender, weight, blood urea nitrogen (BUN),
      creatinine (Cr), sodium (Na), potassium (K) and arterial blood gas (ABG) before
      and after surgery, and their pulse rate (PR) and blood pressure (BP) before,
      during and after surgery. Their urine volume was assessed in the operation room
      and the first 24 h after surgery. The short-term outcome, including BUN and Cr in
      the first 10 days after transplant, have been charted. Both the case (mannitol
      positive donor patient) and the control (mannitol negative) groups were the same
      regarding the results gained for pre- and post-operative parameters. Follow-up
      assessments showed no significant differences in renal function. Based on this,
      we conclude that mannitol administration to donors does not have a beneficial
      effect on the prognosis and short-term outcome of transplantation on recipients;
      therefore, we feel that it should not be advised for kidney donors. 

PMID- 25394431
TI  - Influence of p53 (rs1625895) polymorphism in kidney transplant recipients.
AB  - Reperfusion injury predisposes the kidney allograft to acute rejection. Apoptosis
      is a mechanism that results in graft injury, and TP53 is an important involved
      gene. To determine the association between single nucleotide polymorphism (SNP)
      in the pro-apoptotic protein p53 (rs1625895) and acute rejection in renal
      transplants, we studied 100 recipients of kidney allografts and 100 healthy
      individuals served as controls. The polymorphism was determined by the polymerase
      chain reaction restriction-fragment length polymorphism (PCR-RFLP) test. Overall,
      31 recipients developed rejection. There was no difference in the genotype
      frequencies between the recipients and the controls. However, we found a
      difference of genotype and allele frequencies between recipients with and those
      without rejection. The WW genotype was more frequent in recipients with
      rejection. Although rejection is a complex immunologic event and functional
      importance of SNPs has not been confirmed yet, we suggest that wild type p53 may
      promote apoptosis during inflammation. 

PMID- 25394432
TI  - Trends of elevated parathormone serum titers in hemodialysis patients on
      intensive therapy for bone disease: a multicenter study.
AB  - To determine the prevalence of controlled parathyroid hormone (PTH) serum levels
      with intensified therapy for chronic kidney disease mineral and bone disorder
      (CKD-MBD) in the dialysis population, we studied 563 chronic hemodialysis
      patients recruited from three different dialysis centers from three different
      major cities in the Kingdom of Saudi Arabia. The trend of the routine monthly
      chemistries related to CKD-MBD was evaluated besides the whole-molecule PTH serum
      levels over 28 months (January 2011 to April 2013). The cost ratios of the
      medications to the estimated dialysis total cost were calculated. There were 323
      (57.4%) males in the study, and the mean age of the patients was 50.2+/-15.2
      years; 371 (65.9%) patients were initiated on dialysis before 2011. The causes of
      the original kidney disease included diabetes mellitus in 163 (29%) patients.
      Parathyroidectomy was performed in 23 (4.1%) patients and only six (23%) patients
      underwent the operation during the study period; most of the parathyroidectomies
      (69%) were performed before 2011. The trend of the medians of monthly serum
      levels of calcium, phosphorus, albumin, bicarbonate, alkaline phosphatase, serum
      levels of PTH and vitamin D25 assays showed better control of the levels with
      time. The added cost of cinacalcet was more significant than the other drugs,
      including vitamin D and phosphate binders, but the cost was minimal in comparison
      with the whole dialysis bill. The ratios of the discontinuation rates to the
      total patient-months of treatment for the different drugs were in the range of 3
      4% and mostly due to transient overdosing of medications. We conclude that the
      trends of the median serum levels of PTH and related minerals in the CKD patients
      in our dialysis patients suggested a good inclination toward control and
      prevention of the vascular calcifications prevalent in the CKD-MBD. The
      popularity of use of new drugs such as cinacalcet is promising and does not seem
      to add much to the current out-patient cost of chronic dialysis.

PMID- 25394433
TI  - The relationship between aortic knob width and various demographic, clinical, and
      laboratory parameters in stable hemodialysis patients.
AB  - Accelerated atherosclerosis is very common in hemodialysis (HD) patients and is
      related to morbidity and mortality. The aortic knob width (AKW), which can easily
      be calculated on chest radiographs has also been found to be related to
      atherosclerosis in patients with normal renal function. The importance of AKW in
      HD patients is not known. The current study is aimed to investigate factors
      associated with increased AKW in HD patients. The study participants had their
      medical history taken and a physical examination conducted, with calculation of
      dialysis adequacy and AKW. AKW was calculated from the chest x-rays at the end of
      the dialysis session, when the patients were in their dry weight. A total of 91
      HD patients and 65 patients with normal renal function (as a control group) were
      included. The mean of the AKW was 35.0+/-5.8 mm in HD patients and 26.6+/-4.3 mm
      in the control group (P<0.0001). Stepwise linear regression analysis of both
      groups combined revealed that age (P: 0.001), male gender (P<0.0001), systolic BP
      (P<0.0001), presence of HD treatment (P: 0.016), and albumin levels (P: 0.021)
      were inde-pendently related with increased AKW. On the other hand, in HD patients
      stepwise linear regression showed that age (P<0.0001), pre-dialysis systolic BP
      (P: 0.003), male gender (P<0.0001), being a non-smoker (P: 0.002), total
      cholesterol (P: 0.001), and intact parathormone levels (P: 0.005) were
      independently associated with increased AKW. In conclusion, AKW is increased in
      HD patients when compared with the normal population. These preliminary findings
      may enhance the use of chest radiography as a screening method, and if confirmed,
      can assist risk stratification in HD patients.

PMID- 25394434
TI  - The effect of a membrane dialyzer during hemodialysis on the antioxidant status
      and lipid peroxidation of patients with end-stage renal disease.
AB  - Renal failure is accompanied by oxidative stress, which is caused by enhanced
      production of reactive oxygen species (ROS) and an impaired antioxidant defense.
      We studied 73 hemodialysis (HD) patients (39 males and 34 females) aged 24-75
      years; the patients were randomized into two subgroups according to the type of
      hemodialysis membrane (35 patients were dialyzed on cellulose and 38 patients on
      polysulfone F7/F9 membrane dialyzers) and we assessed their antioxidant and lipid
      peroxidation status levels. The total antioxidant status (TAS) levels including
      whole blood levels of malondialdehyde (MDA) and glutathione (GSH); glutathione
      peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities
      were measured, before and after hemodialysis. The MDA levels significantly
      increased 52.0% and 16.9% post dialysis among the cellulose and the polysulfone
      dialyzer users, respectively, (P<0.05). The TAS levels significantly decreased,
      22.0 and 16.5% in the cellulose and polysulfone dialyzer users, respectively,
      (P<0.05). The erythrocyte SOD activity decreased 25.1 and 19.1% in the cellulose
      and the polysulfone dialyzer users, respectively, (P<0.05). The GSH
      concentrations, post dialysis, decreased 49.9 and 6.8% in the cellulose and
      polysulfone dialyzer users, respectively, (P<0.05). In contrast, the erythrocyte
      activity of CAT, post dialysis, increased 15.0 and 37.3% in the polysulfone and
      the cellulose dialyzer users, respectively, (P<0.05). We conclude that the type
      of the dialysis membrane affects the oxidative status after HD with possible
      consequences on patient morbidity and mortality.

PMID- 25394435
TI  - Percutaneous versus laparoscopic placement of peritoneal dialysis catheters:
      simplicity and favorable outcome.
AB  - Implantation of peritoneal dialysis (PD) catheters via the laparoscopic technique
      is expanding, but none of the studies concerning this technique have compared its
      outcome with the percutaneous insertion done by the nephrologist. We compared the
      technical survival and outcome of 52 PD catheters placed in 43 patients with end
      stage renal disease (ESRD) in our center from March 2006 to October 2007. Of
      these, 27 PD catheters were inserted percutaneously by a nephrologist (group 1)
      and 25 were placed by a surgeon using the conventional laparoscopic technique
      (group 2). Very obese patients, those with previous abdominal surgery, and those
      who refused local anesthesia were excluded from the study. All catheters were
      evaluated for mechanical and infectious complications and the overall technique
      survival was analyzed. The incidence of complications in PD catheters did not
      largely differ between the two groups. Early catheter-related infection episodes
      (within two weeks of catheter placement) occurred in three of 22 (13.6%) patients
      in group 1, versus three of 21 (14.3%) patients in group 2 (P>0.05). The
      incidence of exit site leak was higher in group 2 (19.0%) compared to (4.5%)
      group 1 (P<0.001). Moreover, catheter survival was comparable in both groups
      (81.8% at 12 months and 77.3% at 18 months in group 1) versus (85.7% at 12 months
      and 80.9% at 18 months in group 2) (P>0.05). We conclude that in our study, the
      percutaneous bedside placements of PD catheters done by nephrologists were
      comparable with the laparoscopic insertions performed by surgeons where the high
      risk patients were avoided, and the former provided a safer and more reliable
      access that allowed a rapid initiation of PD.

PMID- 25394436
TI  - Do the outcomes of living donor renal allograft recipients differ with peritoneal
      dialysis and hemodialysis as a bridge renal replacement therapy?
AB  - This study was undertaken to compare the outcomes of living donor renal
      transplant recipients using peritoneal dialysis (PD) and hemodialysis (HD) as a
      bridge modality for renal replacement therapy till renal transplantation. The
      demographic profiles of the recipients and donors, the patients' native kidney
      disease (diabetic versus non-diabetic), duration on dialysis, requirement of anti
      hypertensive drugs, number of blood transfusions, human leukocyte antigen (HLA)
      mismatch status, pre- and post-transplant infectious complications, and post
      transplant outcomes of patients were compared between the two groups. The
      demographic features of the study patients were similar in the two groups. The
      duration of dialysis prior to transplant was significantly longer in the PD group
      than in the HD group of patients. The anti-hypertensive drug requirement was
      lower and the hemoglobin level and residual urine volume at the time of
      transplant were relatively better in the PD patients compared to the HD patients.
      The number of acute rejection episodes, delayed graft function, surgical
      complications, glomerular filtration rate at one month and at the last follow-up,
      were also similar in both groups. The short-term and long-term graft survival was
      similar in both groups of patients. The one-, two-, five-, and eight-year death
      censored graft survival rates of the PD patients were 98, 95, 85, and 73%,
      respectively, and in the HD group of patients, they were 100, 93, 84, and 79%,
      respectively. The one-, two-, five-, and eight-year patient survival rates in the
      PD group were 97, 92, 77, and 66%, respectively, and in the HD group, they were
      97, 92, 79, and 69%, respectively. Our study suggests that the outcomes of the
      living donor renal allograft recipients did not differ between the groups of
      patients who used PD or HD as renal replacement therapy prior to renal
      transplantation. 

PMID- 25394437
TI  - Follow-up study of post-infectious glomerulonephritis in adults: analysis of
      predictors of poor renal outcome.
AB  - Post-infectious glomerulonephritis (PIGN) still remains one of the most common
      glomerulonephritis in the developing world. We studied the epidemiology and
      clinical spectrum of PIGN in adults to identify the clinical, biochemical and
      histological factors that would predict renal outcome. Data of 102 adult PIGN
      patients treated between 2009 and 2011 with a mean follow-up of 12 months (6-36
      months) were analyzed retrospectively. The mean age of the patients was 32.7+/-15
      years, with a male to female ratio of 1.2:1. At presentation, 99% of the patients
      had edema and oliguria, 73% had hypertension, 55% had macrohematuria and 60% had
      nephrotic range proteinuria. About 14% presented with complications (pulmonary
      edema-6%, seizure-1%, dialysis requiring renal failure-7%) and 9% had comorbid
      illness. Sixty percent of the patients had serum creatinine>2 mg/dL at
      presentation, which was persistent in 30% at the end of one week and 68% had hypo
      complementemia. Renal biopsy revealed diffuse proliferative glomerulonephritis in
      70% of the patients. At 12 months, 2% had persistent hypertension, 10% had
      persistent proteinuria and hematuria and 11% had serum creatinine>1.5 mg/dL.
      Univariate analysis with the Fischer Exact test revealed age>40 years, male
      gender, serum creatinine>2 mg/dL at one week, comorbid illness, requirement of
      dialysis, crescents in >30% glomeruli and persistent proteinuria and microscopic
      hematuria at 12 months as significant risk factors for poor renal outcome. Serum
      creatinine>2 mg/dL at one week and persistent proteinuria at 12 months were the
      independent risk factors that predicted poor renal outcome at one year.

PMID- 25394438
TI  - Comparison between three supportive treatments for prevention of contrast-induced
      nephropathy in high-risk patients undergoing coronary angiography.
AB  - Contrast-induced nephropathy is the third most common cause of acute renal
      failure in hospitalized patients. The purpose of this study was to compare three
      supportive treatments for prevention of contrast-induced nephropathy in high-risk
      patients undergoing coronary angiography. In this randomized clinical trial
      study, 150 patients with at least one risk factor, such as, congestive heart
      failure, history of diabetes mellitus, age>65 years or renal failure were
      randomly assigned to three equal groups: First group (Sodium (Na) bicarbonate
      infusion), second group [(N-Acetylcysteine (NAC)+Sodium Chloride (Nacl)], third
      group (Nacl). Angiography was performed with 350 mgI/mL of Iohexol (Omnipaque).
      Serum creatinine (Cr), blood blood urea nitrogen (BUN), and urine pH were
      measured at the start of angiography and 48 hours later. The three groups had no
      significant difference in demographic characteristics or other risk factors
      before intervention (P>0.05). Forty eight hours after exposure, the Cr level
      increased significantly in the Nacl group (P=0.039), while these changes were not
      significant in the other groups (P>0.05). The incidence of contrast-induced
      nephropathy was not statistically significant between all the groups (P=0.944).
      Although the Cr clearance had no statistically significant difference, it was
      lower in the NaCl group. Therefore, Na bicarbonate may be the treatment of choice
      in the prevention of contrast-induced nephropathy, because of less prescribed
      fluid volume and a lesser time required for infusion of the fluid.

PMID- 25394439
TI  - Neurocognitive functions and behavioral profiles in children with nephropathic
      cystinosis.
AB  - Children with nephropathic cystinosis (NCTN) have evidence of defective
      intellectual functions and behavioral disorders. This prospective study was
      performed to detect the cognitive dysfunctions in patients with this rare
      hereditary lysosomal storage disease, define their behavioral phenotypes, and
      study the findings on magnetic resonance imaging (MRI) of the brain. Thirteen
      patients with confirmed diagnosis of cystinosis (mean age+/-SD 5.9+/-3.0, range
      1.5-12 years) were subjected to the Stanford Binet test, Porteus Maze test, Child
      Behavior Checklist, and MRI brain. Thirteen age- and sex-matched children served
      as the control subjects (mean age+/-SD 5.9+/-2.9, range 1.7-12 years). The
      intelligence quotient (IQ) was significantly lower in patients with cystinosis
      (P<0.001), with a significant defect in verbal (language, memory, and
      comprehension) and non-verbal abilities (visual perception and visiospatial and
      motor performance). A discrepancy between both abilities was detected--the non
      verbal ability being lower; however, it did not reach statistical significance.
      Furthermore, analysis revealed the visiospatial ability to be significantly lower
      compared to the visual perception. In comparison to healthy controls, children
      with NCTN had evidence of increased incidence of behavioral problems, mainly
      social (P=0.023). An MRI of the brain revealed varying degrees of atrophic
      changes in seven patients. Patients with NCTN need a wider scope of attention and
      care, encompassing not only the metabolic multisystem derangement, but also the
      neuropsychological impairment in the context of multidisciplinary management.
      This approach is crucial in formulating comprehensive plans for social and
      educational rehabilitation.

PMID- 25394440
TI  - Preinduction hemodynamic fluctuations in renal transplant recipients--comparison
      of two combined anesthesia regimens.
AB  - An ideal anesthetic technique for a renal allograft recipient must ensure
      hemodynamic stability, enhance graft reperfusion, and provide good postoperative
      pain relief. Hence, a combined general and epidural anesthesia is preferred. In
      our clinical practice, it has been observed that in chronically ill end-stage
      renal disease (ESRD) patients, a bolus injection of epidural local anesthetics
      invariably necessitated the use of vasopressor agents. Such hemodynamic
      fluctuations may not be favorable for the graft. A prospective, randomized,
      double-blind study was conducted on 50 ESRD adults, 18-55 years, scheduled for
      elective live related kidney transplantation. The patients randomly received
      either epidural fentanyl (50 MUg) and normal saline (10 mL) or epidural fentanyl
      (50 MUg) and bupivacaine (0.5%; 10 mL) followed by standardized general
      anesthesia. Perioperative hemodynamics and vasopressor requirements were compared
      with both regimens. Early graft function was assessed by the onset of diuresis
      after declamping, serial creatinine values, glomerular filtration rate, and 24
      hour urine output estimation. In the preoperative period, statistically
      significant reduction in the mean arterial pressure and the cardiac index
      occurred in 60% of the patients receiving epidural bupivacaine boluses. These
      hypotensive episodes required a therapeutic intervention prior to general
      anesthesia, that is, intravenous mephenteramine (3-6 mg; 9.60+/-2.32 mg) and
      crystalloid infusion (189.28+/-21.29 mL). Intraoperative hemodynamic parameters,
      surgical blood loss, and transplanted kidney function were comparable between the
      groups. We concluded that the use of regional anesthetics needed to administered
      cautiously in renal transplant recipients to maintain hemodynamic parameters.

PMID- 25394441
TI  - Performance of QuantiFERON TB Gold test in detecting latent tuberculosis
      infection in brain-dead organ donors in Iran: a brief report.
AB  - With regard to the significant morbidity and mortality due to tuberculosis in
      lung transplant recipients, the identification of brain-dead organ donors with
      latent tuberculosis by use of the QuantiFERON TB Gold (QFT-G) test may be of help
      to reduce the risk of TB reactivation and mortality in lung recipients. This
      study was conducted in the National Research Institute of Tuber-culosis and Lung
      Diseases (NRITLD) in Iran, from January to March 2013. A total of 38 conse-cutive
      brain-dead donors, not currently infected with active tuberculosis, were
      recruited. The medi-cal records of all the study enrollees were reviewed. A whole
      blood IFN- release assay (IGRA) in reaction to early secreted antigenic target 6
      (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7 antigens, was performed
      and the released Interferon- was measured via enzyme-linked immunosorbent assay
      (ELISA). The data was analyzed with QFT-G software which was provided by the
      company. The demographic, characteristics and other variables were entered into
      SPSS version 11.5. The QFT-G test results of three donors (7.9%) turned out to be
      positive, negative for 24 donors (63.1%), and indeterminate for 11 cases (28.9%).
      Our study revealed the potential advantages of QFT-G in lowering the incidence of
      donor-derived post-transplant tuberculosis among lung recipients. However, a high
      rate of indeterminate results restricted the performance of QFT-G in this study. 

PMID- 25394442
TI  - Post-partum acute kidney injury.
AB  - To determine the risk factors, course of hospital stay and mortality rate among
      women with post-partum acute kidney injury (AKI), we studied (of 752 patients
      with AKI admitted to a tertiary care center during the study period between
      November 2009 and August 2012) 27 (3.59%) women with post-partum AKI. The data
      regarding age, parity, cause of renal failure, course of hospital stay and
      requirement of dialysis were recorded. Sepsis was the major cause (70.3%) of post
      partum AKI. Other causes included disseminated intravascular coagulation (55.5%),
      pre-eclampsia/eclampsia (40.7%), ante- and post-partum hemorrhage (40.7% and
      22.2%) and hemolytic anemia and elevated liver enzymes and low platelet count
      syndrome (29.6%); most patients had more than one cause of AKI. We found a very
      high prevalence (18.5%) of cortical necrosis in our study patients. A significant
      correlation was also found between the creatinine level on admission and the
      period of onset of disease after delivery. In conclusion, several factors are
      involved in causing post-partum AKI in our population, and sepsis was the most
      common of them. 

PMID- 25394443
TI  - Skin, subcutaneous tissue, and allograft infection with Mycobacterium fortuitum
      in a renal transplant recipient.
AB  - Different types of skin disorders are prevalent among kidney transplant
      recipients. The development of nodular skin lesions in these patients would
      usually raise a suspicion of Kaposi's sarcoma. We report a patient, who presented
      with nodular skin lesions one year post transplant, but the biopsy revealed a
      rare diagnosis - Mycobacterium fortuitum (M. fortuitum) infection of the skin,
      subcutaneous, and renal allograft. He was treated successfully with an initial
      two-week course of intravenous cefoxitin, followed by a six-month course of
      ciprofloxacin, clarithromycin, and co-trimoxazole. There are a few reported cases
      of M. fortuitum infection in renal transplant recipients in the literature -
      notably urinary tract infection, allograft infection, and psoas abscess, but to
      the best of our knowledge this is the first case demonstrating extensive
      infection involving the skin, subcutaneous tissue, and renal allograft.
      Physicians vested with the care of renal transplant patients should be aware of
      this rare infection in these patients. 

PMID- 25394444
TI  - Double primary carcinoma in a renal allograft recipient.
AB  - We report a renal allograft recipient on triple immunosuppression with
      prednisolone, azathioprine and cyclosporine who presented with ductal
      infiltrating carcinoma of the right breast eight years post-transplant, followed
      two years later with left ovarian papillary carcinoma. 

PMID- 25394445
TI  - Continuous venovenous hemodiafiltration along with charcoal hemoperfusion for the
      management of life-threatening lercanidipine and amlodipine overdose.
AB  - Overdose with calcium channel blockers is uncommon, but is associated with high
      mortality. The management includes fluid resuscitation, calcium gluconate,
      glucagon, vasopressors, and high-dose insulin-euglycemia therapy. We describe a
      rare case of massive overdose of lercanidipine with shock, refractory to
      conventional therapies and multi-organ failure. Charcoal hemoperfusion with
      continuous venovenous hemodiafiltration was then used successfully and the
      patient showed remarkable recovery. 

PMID- 25394446
TI  - Snake bite complicated by acute kidney injury secondary to necrotizing
      glomerulonephritis.
AB  - We present a 38-year-old man who presented to the emergency department with
      complaints of a snake bite. He developed acute kidney injury (AKI) and the kidney
      biopsy showed necrotizing glomerulonephritis, which is rarely reported in AKI
      after snake bite. 

PMID- 25394447
TI  - Concurrent emphysematous pyelonephritis and thigh necrotizing fasciitis after
      intramuscular administration of diclofenac.
AB  - Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening soft tissue
      infection. NF may result from any injury to the skin or from hematogenous spread.
      However, con-current emphysematous pyelonephritis and necrotizing fasciitis of
      the left thigh has not been reported. We report a case of emphysematous
      pyelonephritis and necrotizing fasciitis of the left thigh after intramuscular
      administration of diclofenac that improved with aggressive management including
      broad-spectrum antibiotics, nephrectomy and surgical intervention.

PMID- 25394448
TI  - Invasive Saccharomyces cerevisiae infection: a friend turning foe?
AB  - We report a very rare case of acute pyelonephritis in a 51-year-old female with a
      history of chronic kidney disease (CKD) and diabetes caused by a normally benign
      and a well-known human commensal organism, Saccharomyces cerevisiae that is very
      often prescribed as a probiotic in modern medical practice. The causal role of S.
      cerevisiae was confirmed by its isolation in blood, urine, stool as well as
      vaginal swabs thus proving its virulent nature in suitable situations. 

PMID- 25394449
TI  - Warburg's effect on solid tumors.
AB  - Lactic acidosis is the result of imbalance between the systemic formation of
      lactate and its hepatic metabolism. In cancer patients, lactic acidosis is mainly
      associated with hematologic malignancies (leukemia and lymphomas) and the
      mechanism is known as Warburg's effect. We report a 76-year-old male known to
      have hypertension and coronary artery disease, who presented with abdominal
      distension and lactic acidosis. His initial evaluation showed multiple liver
      masses that were biopsied and the patient was diagnosed with undifferentiated
      carcinoma of unknown primary, involving the liver. The patient had progression of
      lactic acidosis leading to his death on day-15. As the lactic acidosis was not in
      the setting of hypoxia or hemodynamic instability, we made the diagnosis of
      malignancy-associated type B lactic acidosis, also known as the Warburg's effect.
      Warburg's effect can occur in solid cancer if the tumor involves the liver. It
      has bad prognostic implications. The use of intravenous bicarbonate as a
      temporary measure is of controversial benefit, as it can potentially worsen the
      metabolic acidosis and its use should be limited to patients with very low pH. In
      cancer patients, the use of lactatebased intravenous fluids can be potentially
      harmful and can increase the risk of tumor metastasis, at least in animal
      malignancy models. 

PMID- 25394450
TI  - Retroperitoneum: a forgotten and fatal aspect of kidney biopsy.
AB  - A kidney biopsy is an important tool for nephrologists in the diagnosis of renal
      conditions, but not without the risk of bleeding due to its invasive nature.
      There is abundance of literature on bleeding complications secondary to this
      procedure in high-risk patient groups such as amyloidosis and chronic
      hypertension. An undefined and unrecognized risk is a peritoneal penetration. We
      report here a case where, despite adequately preparing a patient for a kidney
      biopsy, distortion of the peritoneum and retroperitoneum from previous surgery
      resulted in a fatal outcome. This was due to loss of peritoneal integrity and the
      consequent loss of local anatomical hemostatic mechanism. 

PMID- 25394451
TI  - Reno-invasive fungal infection presenting as acute renal failure: importance of
      renal biopsy for early diagnosis.
AB  - Renal zygomycosis, caused by invasive fungi, is a rare and potentially fatal
      infection. The patient usually presents with non-specific symptoms and renal
      failure. A 34-year-old male non-diabetic and without any predisposing factors for
      systemic fungal infection presented to the emergency department with diffuse
      abdominal pain, high-grade fever and acute renal failure with a serum creatinine
      of 6.5. A computed tomography showed bilateral diffuse globular nephromegaly. A
      urine smear for fungal examination showed right angle branching hyphae and kidney
      biopsy showed fungal hyphae within the glomeruli, tubules and interstitium.
      Although radiological investigations can give us a clue, the definitive diagnosis
      can only be made by kidney biopsy. A high index of suspicion and timely diagnosis
      is important for a proper management.

PMID- 25394452
TI  - Ocular changes in renal allograft recipients and patients of chronic kidney
      disease.

PMID- 25394453
TI  - Burkitt's lymphoma developing post liver transplantation: posttransplant
      lymphoproliferative disorders international survey.

PMID- 25394454
TI  - Significance of CD20 expression by lymphoproliferative lesions developing after
      liver transplantation: post-transplant lymphoproliferative disorders
      international survey.

PMID- 25394455
TI  - Eosinophilic cystitis and idiopathic hypereosinophilic syndrome in an eight-year
      old girl.

PMID- 25394456
TI  - Macrothrombocytopenia, psychomotor retardation, and nephropathy: a novel familial
      syndrome.

PMID- 25394457
TI  - A case of minimal change disease complicated by acute kidney injury in systemic
      lupus erythematosus.

PMID- 25394458
TI  - Irreversible fatal renal failure resulting from isolated renal mucormycosis.

PMID- 25394459
TI  - Impact of hepatitis C infection on renal transplant patients: a single-center
      experience in Libya.
AB  - The objective of this study was to assess the effect of hepatitis C virus (HCV)
      infection on graft and patient survival in a cohort of Libyan renal transplant
      recipients. Medical records of 241 renal transplant (RT) patients who have been
      followed-up at the Benghazi Nephrology Center up to February 2010 were reviewed.
      Based on the presence or absence of anti-HCV antibodies and HCV-RNA in the serum,
      patients were divided into two groups: HCV-positives and HCV-negatives. Anti-HCV
      antibodies were detected by the enzyme-linked immunosorbent assay technique and
      HCV-RNA by the polymerase chain reaction. Of the 241 RT patients, 162 were male
      and 79 were female. One hundred and ten patients (45.6%) were HCV-positives and
      131 (54.4%) were HCV-negatives. Acute graft rejection was significantly higher
      among HCV-negative than HCV-positive patients (42 patients versus 28 patients,
      respectively; P<0.001). Conversely, chronic graft rejection was higher among HCV
      positives than that among HCV-negative patients (35 patients versus 24 patients,
      respectively; P<0.05), and this difference became more significant after a 12
      month period of transplantation (P<0.01). Seventeen patients died during the
      follow-up: Seven HCV-positives (6.3%) and 10 HCV-negatives (7.6%), and there was
      no significant difference in the death rate following RT between the two groups
      (P=0.08). Among the seven deaths of HCV-positives, liver disease-related
      complications were the main cause of death in three (42.8%) HCV-positive patients
      compared with none in the HCV-negative patients. The presence of HCV infection
      influenced chronic graft survival in RT patients and a higher proportion of HCV
      infected patients had hepatic dysfunctions after RT. An increase in fatal liver
      complications was noted in HCV-positive patients with RT. In addition to pre-RT
      specific therapy of HCV infection, all measures should be taken to prevent HCV
      infection pre- and post-RT. HCV-infected RT recipients need close monitoring for
      graft and liver function to prolong allograft and patient survival.

PMID- 25394460
TI  - Fifteen years of kidney biopsies in children: a single center in Egypt.
AB  - This study retrospectively investigates the indications and results of renal
      biopsy in children to determine the patterns of childhood kidney disease in a
      single tertiary children's hospital in Egypt. We included all the patients who
      underwent ultrasound-guided renal biopsy from 1998 to 2012. All the kidney
      biopsies were studied under light microscopy, while immunofluorescence and
      electron microscopy were performed when indicated. A total of 1246 renal biopsies
      were performed over 15 years, on 1096 patients. The mean age of the patients at
      the time of biopsy was 9.2+/-3.7 years. The main indication for a biopsy was the
      steroid-resistant nephrotic syndrome (n=354, 28.4%), followed by the atypical
      nephrotic syndrome (n=250, 20.1%), and renal abnormalities in the systemic
      diseases (n=228, 18.3 %). In the 1226 pathologically diagnosed specimens, primary
      glomerulonephritis was the most common finding (n=826, 67.4%), followed by
      secondary glomerulonephritis (n=238, 19.4%). The most common causes of primary
      glomerulonephritis were Minimal Change Disease (MCD) (n=267, 21.8%), diffuse
      proliferative glomerulonephritis (n=188, 15. 3%), and focal proliferative
      glomerulonephritis (n=164, 13.3%). Lupus nephritis (n=209, 17%) was the most
      common cause of secondary glomerulonephritis. We conclude that the steroid
      resistant nephrotic syndrome was the most frequent indication for biopsy and
      minimal change disease was the most common histopathological finding in our
      population.

PMID- 25394461
TI  - Hypertension care in Aseer region, Saudi Arabia: barriers and solutions.
AB  - The aim of this study is to assess the current situation of hypertension (HTN)
      care, to explore the barriers and to suggest the practical solutions to improve
      the quality of HTN care in primary health care centers (PHCC) in the Aseer
      region, KSA. This cross-sectional study was conducted in PHCCs in this region in
      2010. Data collection sheets used to achieve the aims of this study consisted of
      three checklists, the first one derived from the quality assurance manual and HTN
      records used at the PHCCs giving details of the structural base of HTN care.
      Satisfaction with HTN care was assessed by using a five-point Likert scale
      questionnaire, while the third part was assessed by a checklist designed for the
      HTN care processes. Data were coded, entered and analyzed using SPSS version 16.
      The total number of HTN patients registered at PHCCs in Aseer region was 23,156
      patients. Of them, 15,942 (69%) had files at PHCCs. Most of the essential
      infrastructures were acceptable, except training of doctors and nurses on HTN,
      which were 75% and 89%, respectively. About 40% of patients were on Beta blockers
      or ACE inhibitors and 30% were being given Aspirin in addition. HTN was
      uncontrolled among 45% of patients, while the defaulter rate was 22%. The rates
      of complications ranged from 0.7% for stroke to 7% for ischemic heart diseases.
      It was found that more than one-third of the patients had obesity and diabetes,
      while 10% suffered from dyslipidemia. Health teams were unsatisfied with the
      community participation (43%), patient compliance with appointment (32%) and
      coordination with hospitals (20%). They were satisfied with the health team
      (85%), while satisfaction with other items ranged from 60% to 75%. This study
      revealed that HTN patients received insufficient care, which could be attributed
      to many different barriers. In order to improve the quality of HTN care for HTN,
      these barriers should be overcome by implementation of the recommendations. 

PMID- 25394462
TI  - Survival of living donor renal transplant recipients in Sri Lanka: a single
      center study.
AB  - Chronic kidney disease is one of the main public health concerns in Sri Lanka. In
      comparison with dialysis, successful kidney transplantation improves both patient
      survival and quality of life, relieves the burden of dialysis in patients
      suffering from end-stage renal disease and decreases the cost of healthcare to
      the society and government. The objective of this retrospective cohort study was
      to evaluate graft and patient survival rates in patients who were transplanted
      from living donors at the Nephrology Unit of the National Hospital of Sri Lanka
      from January 2005 to January 2011. Data were collected using an interviewer
      administered questionnaire and through a review of past medical records. The
      Kaplan-Meier method was used to determine the survival rate, the log rank test
      was used to compare survival curves and the Cox proportional hazard model was
      used for multivariate analysis. Mean follow-up was 26.44+/-16.6 months. The five
      year death-censored graft survival of kidney transplant recipients from living
      donors in our center was 93.5% and the five-year patient survival was 82.2%,
      which is comparable with other transplant programs around the world. The number
      of acute rejection episodes was an independent risk factor for graft survival.
      Delayed graft function, younger recipient age and unknown cause of end-stage
      renal disease were found to be risk factors for graft failure but after adjusting
      for confounding factors, and the difference was not apparent.

PMID- 25394463
TI  - Trends in hepatitis C infection among hemodialysis patients in Senegal: results
      of a decade of prevention.
AB  - Chronic kidney disease is an emerging public health issue in Africa. At end-stage
      renal disease (ESRD), patients need hemodialysis (HD), which may expose them to
      blood transmitted infections, such as the hepatitis C virus (HCV). Sub-Saharan
      Africa has the highest HCV prevalence in the world, but data on HD patients is
      scarce and shows an exceptionally high rate in Senegal. To assess the efficacy of
      preventive measures in reducing HCV infection among dialysis patients, we
      retrospectively conducted a cross-sectional study in three Senegalese HD centers,
      including all HD patients who performed HCV serology between 1 st and 31 st
      August 2011. The demographical, clinical, and biological data were collected for
      each patient. We included 106 patients with a mean age of 43.4+/-15.8 years
      (range from 18 to 80 years), with 52.8% males. HD vintage was 60.5+/-15 months
      (range from six to 206 months). The main causes of kidney disease included
      nephrosclerosis (36%) and diabetes (24%). The prevalence of HCV was 5.6%, with
      one patient co-infected with the hepatitis B virus. After adjusting for age and
      sex, HD vintage was the only risk factor for HCV infection, while nutritional
      status and the number of blood transfusions did not significantly correlate with
      HCV infection. We conclude that during the past decade, the prevalence of HCV
      infection in HD patients living in Senegal has declined considerably, mainly
      because of improved transfusion measures and better clinical practice in the HD
      centers. Such efforts should be maintained and reinforced to reduce the
      seroprevalence of HCV infection.

PMID- 25394464
TI  - Quality of life of patients with end-stage renal disease in Guinea.
AB  - This questionnaire-based study included 69 patients from the Republic of Guinea
      with end-stage renal disease (ESRD) and was conducted over 12 months. The factors
      that affected their quality of life (QoL) were determined. The included ESRD
      patients had an estimated creatinine clearance (CCr) of <15 mL/minute using MDRD
      formula. We used the SF36 question-naire and classified the results into two
      groups: Scores<50/100 as poor QoL and scores 50/100 as good QoL. Factors that
      determined the QoL were cessation of all activities and additional effort
      required, severe or mild pain, good or bad health, and reduced or not reduced
      social and physical activities. Of the 69 patients, 32 (46.3%) had a good QoL and
      37 (53.7%) had a poor QoL. The estimated CCr was similar in both groups. The
      average age of the poor QoL group was 54+/-4 years, the good-QoL group's average
      age was of 47.6+/-4 years (P=0.01). Patients with a good QoL had better overall
      health, but this was not statistically significant [OR=0.42 (0.14-1.28); P=0.14].
      Patients with a poor QoL had more severe pain (P=0.002); however, good QoL did
      not protect against mental problems [OR=46.67 (8.18-351.97); P=0.0001]. Mental
      status (P=0.01) and social activities (P=0.001) were reduced, and there were more
      comorbidities in the poor-QoL group (29.7%, with >4, P=0.01). Good QoL was
      associated with younger age, fewer comorbidities, less severe physical pain, and
      fewer physical or social limitations. QoL could be increased by improving
      comorbidity treatments, giving more effective pain control, and providing more
      assistance for social and physical limitations.

PMID- 25394465
TI  - Black water fever associated with acute renal failure among Congolese children in
      Kinshasa.
AB  - Acute renal failure (ARF) is reported in some severe forms of malaria such as
      black water fever (BWF). It is associated with a high mortality rate and can be
      managed effectively with adequate renal replacement. A prospective survey of
      children with dark urine after a malarial infection with Plasmodium falciparum
      was coupled with a chart review study of patients managed in the past 11 years in
      the Pediatrics' Kinshasa University Hospital. Eighty-nine cases of ARF were
      identified, but data from only 63 patients were available, of whom 44 (69.8%) had
      severe malaria (39 with BWF and 5 with cerebral malaria). The mean age of the
      patients was 8.2+/-1.73 years. Of the 39 cases of BWF, an association with
      quinine ingestion was observed in 32 children (82%). Urea and creatinine levels
      were elevated in all cases (135.4+/-88.2 and 3.83+/-2.81 mg/dL, respectively).
      Oligo-anuria was observed in 44.4%, severe metabolic acidosis (bicarbonate<15
      mEq/L) in 61.5% and hyponatremia (<130 mEq/L) in 33.3%. Peritoneal dialysis was
      required in 36 patients, including 20 with BWF. The remaining patients were
      managed with conservative treatment. Twenty-eight children (44.4%), including 20
      on dialysis, fully recovered and 14 died (22.2%), including eight cases of BWF.
      Our study suggests that ARF is commonly associated with BWF in Congolese
      children. Elevated urea and creatinine and severe metabolic acidosis were
      observed more often than other clinical/metabolic disturbances. Severe renal
      impairment remains a significant complication with a high mortality rate in low
      resource settings.

PMID- 25394466
TI  - Effects of the suppression of lactate dehydrogenase A on the growth and invasion
      of human gastric cancer cells.
AB  - Lactate dehydrogenase A (LDH-A), which regulates glycolytic flux by catalyzing
      pyruvate to lactate in the cytoplasm, is believed to be one of the highly
      attractive therapeutic targets for cancers. Firstly, we detected the expression
      of LDH-A in gastric cancer (GC) cells. LDH-A inhibitor oxamate was then used to
      suppress the LDH-A activity in GC cells. Cell proliferation, lactic acid
      production, Transwell migration assay and apoptosis were assessed, respectively.
      The results showed that inhibition of LDH-A by oxamate decreased the lactate
      production. In the presence of glucose, oxamate inhibited cell proliferation in a
      dose-dependent manner. Flow cytometry assay further confirmed a pro-apoptotic
      effect of oxamate, and this was likely through increased expression of Bax,
      activated caspase-3, and decreased expression of Bcl-2. Therefore, we believe
      that oxamate inhibits cell growth, suppresses tumor invasion, and induces
      apoptosis in GC cells. LDH-A may be a potential therapeutic target for GC.

PMID- 25394467
TI  - Synthesis, characterization and in vitro and in vivo investigation of C3F8-filled
      poly(lactic-co-glycolic acid) nanoparticles as an ultrasound contrast agent.
AB  - The present study aimed to prepare perfluoropropane (C3F8)-filled poly(lactic-co
      glycolic acid) (PLGA) nanoparticles and investigate the feasibility of using PLGA
      nanoparticles as an ultrasound contrast agent. The PLGA nanoscale ultrasound
      contrast agent was prepared using a modified double-emulsion solvent evaporation
      method. Camphor in the form of a sublimable porogen was added to render the
      nanoparticles hollow and enable C3F8 gas introduction. Various physicochemical
      properties of PLGA nanoparticles, including morphology, size and dispersion, were
      analyzed by electron microscopy and dynamic laser scattering. In vitro ultrasound
      imaging of C3F8-filled PLGA nanoparticles was also investigated under various
      imaging conditions. Further in vivo ultrasound imaging was conducted on male rats
      following intratesticular injection of PLGA nanoparticles. C3F8-filled PLGA
      nanoparticles with a mean diameter of 152.0+/-58.08 nm were obtained. Electron
      microscopy revealed spherical-shaped nanoparticles with smooth surfaces, a
      capsular morphology and a large hollow within. In vitro ultrasound imaging of
      hollow PLGA nanoparticles indicated marked signal enhancement. Local intensity of
      the acoustical signal continued to increase during PLGA-nanoparticle injection
      into the testicle and the ability of hollow PLGA nanoparticles to enhance
      ultrasound imaging in vivo was demonstrated. The enhancement image of testicular
      tissue following injection with C3F8-filled PLGA nanoparticles was sustained for
      a minimum of five minutes. In conclusion, the hollow C3F8-filled PLGA
      nanoparticles were demonstrated to have potential for applications as a novel
      ultrasound contrast agent.

PMID- 25394468
TI  - Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion.
AB  - Synaptic adhesion molecules orchestrate synaptogenesis. The presynaptic leukocyte
      common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs)
      regulate synapse development by interacting with postsynaptic Slit- and Trk-like
      family proteins (Slitrks), which harbour two extracellular leucine-rich repeats
      (LRR1 and LRR2). Here we identify the minimal regions of the LAR-RPTPs and
      Slitrks, LAR-RPTPs Ig1-3 and Slitrks LRR1, for their interaction and synaptogenic
      function. Subsequent crystallographic and structure-guided functional analyses
      reveal that the splicing inserts in LAR-RPTPs are key molecular determinants for
      Slitrk binding and synapse formation. Moreover, structural comparison of the two
      Slitrk1 LRRs reveal that unique properties on the concave surface of Slitrk1 LRR1
      render its specific binding to LAR-RPTPs. Finally, we demonstrate that lateral
      interactions between adjacent trans-synaptic LAR-RPTPs/Slitrks complexes observed
      in crystal lattices are critical for Slitrk1-induced lateral assembly and
      synaptogenic activity. Thus, we propose a model in which Slitrks mediate
      synaptogenic functions through direct binding to LAR-RPTPs and the subsequent
      lateral assembly of LAR-RPTPs/Slitrks complexes. 

PMID- 25394469
TI  - Automatic quantitative analysis of t-tubule organization in cardiac myocytes
      using ImageJ.
AB  - The transverse tubule system in mammalian striated muscle is highly organized and
      contributes to optimal and homogeneous contraction. Diverse pathologies such as
      heart failure and atrial fibrillation include disorganization of t-tubules and
      contractile dysfunction. Few tools are available for the quantification of the
      organization of the t-tubule system. We developed a plugin for the ImageJ/Fiji
      image analysis platform developed by the National Institutes of Health. This
      plugin (TTorg) analyzes raw confocal microscopy images. Analysis options include
      the whole image, specific regions of the image (cropping), and z-axis analysis of
      the same image. Batch analysis of a series of images with identical criteria is
      also one of the options. There is no need to either reorientate any specimen to
      the horizontal or to do a thresholding of the image to perform analysis. TTorg
      includes a synthetic "myocyte-like" image generator to test the plugin's
      efficiency in the user's own experimental conditions. This plugin was validated
      on synthetic images for different simulated cell characteristics and acquisition
      parameters. TTorg was able to detect significant differences between the
      organization of the t-tubule systems in experimental data of mouse ventricular
      myocytes isolated from wild-type and dystrophin-deficient mice. TTorg is freely
      distributed, and its source code is available. It provides a reliable, easy-to
      use, automatic, and unbiased measurement of t-tubule organization in a wide
      variety of experimental conditions.

PMID- 25394470
TI  - Characterization of a subpopulation of developing cortical interneurons from
      human iPSCs within serum-free embryoid bodies.
AB  - Production and isolation of forebrain interneuron progenitors are essential for
      understanding cortical development and developing cell-based therapies for
      developmental and neurodegenerative disorders. We demonstrate production of a
      population of putative calretinin-positive bipolar interneurons that express
      markers consistent with caudal ganglionic eminence identities. Using serum-free
      embryoid bodies (SFEBs) generated from human inducible pluripotent stem cells
      (iPSCs), we demonstrate that these interneuron progenitors exhibit morphological,
      immunocytochemical, and electrophysiological hallmarks of developing cortical
      interneurons. Finally, we develop a fluorescence-activated cell-sorting strategy
      to isolate interneuron progenitors from SFEBs to allow development of a purified
      population of these cells. Identification of this critical neuronal cell type
      within iPSC-derived SFEBs is an important and novel step in describing cortical
      development in this iPSC preparation. 

PMID- 25394471
TI  - Human SLC4A11-C functions as a DIDS-stimulatable H+(OH-) permeation pathway:
      partial correction of R109H mutant transport.
AB  - The SLC4A11 gene mutations cause a variety of genetic corneal diseases, including
      congenital hereditary endothelial dystrophy 2 (CHED2), Harboyan syndrome, some
      cases of Fuchs' endothelial dystrophy (FECD), and possibly familial keratoconus.
      Three NH2-terminal variants of the human SLC4A11 gene, named SLC4A11-A, -B, and 
      C are known. The SLC4A11-B variant has been the focus of previous studies. Both
      the expression of the SLC4A11-C variant in the cornea and its functional
      properties have not been characterized, and therefore its potential
      pathophysiological role in corneal diseases remains to be explored. In the
      present study, we demonstrate that SLC4A11-C is the predominant SLC4A11 variant
      expressed in human corneal endothelial mRNA and that the transporter functions as
      an electrogenic H(+)(OH(-)) permeation pathway. Disulfonic stilbenes, including
      4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS), 4,4'
      diisothiocyanatodihydrostilbene-2,2'-disulfonate (H2DIDS), and 4-acetamido-4'
      isothiocyanato-stilbene-2,2'-disulfonate (SITS), which are known to bind
      covalently, increased SLC4A11-C-mediated H(+)(OH(-)) flux by 150-200% without
      having a significant effect in mock-transfected cells. Noncovalently interacting
      4,4'-diaminostilbene-2,2'-disulfonate (DADS) was without effect. We tested the
      efficacy of DIDS on the functionally impaired R109H mutant (SLC4A11-C numbering)
      that causes CHED2. DIDS (1 mM) increased H(+)(OH(-)) flux through the mutant
      transporter by ~40-90%. These studies provide a basis for future testing of more
      specific chemically modified dilsulfonic stilbenes as potential therapeutic
      agents to improve the functional impairment of specific SLC4A11 mutant
      transporters. 

PMID- 25394472
TI  - Identification and characterization of the minimal 5'-regulatory region of the
      human riboflavin transporter-3 (SLC52A3) in intestinal epithelial cells.
AB  - The human riboflavin (RF) transporter-3 (product of the SLC52A3 gene) plays an
      important role in intestinal RF absorption. Our aims in this study were to
      identify the minimal 5'-regulatory region of the SLC52A3 gene and the regulatory
      element(s) involved in its activity in intestinal epithelial cells, as well as to
      confirm promoter activity and establish physiological relevance in vivo in
      transgenic mice. With the use of transiently transfected human intestinal
      epithelial HuTu 80 cells and 5'-deletion analysis, the minimal SLC52A3 promoter
      was found to be encoded between -199 and +8 bp (using the start of the
      transcription start site as position 1). Although several putative cis-regulatory
      elements were predicted in this region, only the stimulating protein-1 (Sp1)
      binding site (at position -74/-71 bp) was found to play a role in promoter
      activity, as indicated by mutational analysis. Binding of Sp1 to the minimal
      SLC52A3 promoter was demonstrated by means of EMSA and supershift assays and by
      chromatin immunoprecipitation analysis. Studies with Drosophila SL2 cells (which
      lack Sp activity) confirmed the importance of Sp1 in driving the activity of the
      SLC52A3 minimal promoter; they further showed that Sp3 can also do the
      activation. Finally, with the use of luciferase gene fusions, the activity of the
      cloned SLC52A3 promoter was confirmed in vivo in transgenic mice. These studies
      report, for the first time, on the identification and characterization of the
      SLC52A3 promoter and also demonstrate the importance of Sp1 in regulating its
      activity in intestinal epithelial cells. 

PMID- 25394473
TI  - Systemic pentraxin-3 levels reflect vascular enhancement and progression in
      Takayasu arteritis.
AB  - INTRODUCTION: Progression of arterial involvement is often observed in patients
      with Takayasu arteritis (TA) thought to be in remission. This reflects the
      failure of currently used biomarkers and activity criteria to detect smouldering
      inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble
      pattern recognition receptor produced at sites of inflammation and could reveal
      systemic as well as localized inflammatory processes. We verified whether the
      blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with
      Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by
      signal enhancement after contrast media administration, and the progression of
      arterial involvement. METHODS: A cross-sectional single-centre study was carried
      out on 42 patients with TA that comprised assessment of PTX3, of CRP and
      erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20
      patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular
      imaging was carried out by magnetic resonance angiography, doppler
      ultrasonography and computed tomography angiography. RESULTS: Patients with TA
      and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P
      = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of
      CRP. Patients with active systemic TA had significantly higher concentrations of
      CRP but similar levels of PTX3 than patients with quiescent disease. In contrast,
      patients with vascular inflammation detectable at imaging had higher PTX3
      concentrations (P = 0.016) than those in which vessel inflammation was not
      evident, while CRP levels were similar. The concentration of PTX3 but not that of
      CRP was significantly higher in TA patients with worsening arterial lesions that
      were not receiving antagonists of tumor necrosis factor-alpha or interleukin-6.
      CONCLUSIONS: Arterial inflammation and progression of vascular involvement
      influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the
      burden of systemic inflammation. These results support the contention that PTX3
      reflects different aspects of inflammation than CRP and might represent a
      biomarker of actual arteritis in TA.

PMID- 25394475
TI  - The effects of foot type and heritability on balance and plantar pressure
      distribution of female twins.
AB  - AIM: Posture and plantar pressure distribution can influence several factors,
      including both foot type and heritability. Therefore, the purpose was to assess
      the influence of foot type and heritability and their effects on foot
      characteristics. Static and dynamic balance and plantar pressure distribution was
      assessed, and the participants were pairs of female twins. METHODS: Sixteen
      monozygotic and fourteen dizygotic pairs with no history of injuries were
      included in this causal-comparative study, divided into three foot types by
      navicular drop test: pes planus, pes rectus and pes cavus. Static balance was
      measured using the stork test and dynamic balance using the SEBT test. Plantar
      pressure distributions were measured by the emed platform. Two-way ANOVA, F test,
      heritability estimate, intraclass correlation coefficient and Fisher Z test were
      used for statistical analysis. RESULTS: No significant differences were found
      between foot types or zygosities in static and dynamic balance and peak pressure
      (P>0.05). Within-pair variances were significantly different in dynamic balance
      in PL and L directions (P<0.05). Heritability was 0.43, 0.52, 0.62, 0.65 and 0.39
      in static balance and dynamic balance variables in P, PL, L and mean of eight
      directions, respectively. Genetic factors revealed no influence on peak pressure.
      Within-pair correlations were significantly different in dynamic balance results
      in PL and L directions (P<0.05). CONCLUSION: Foot type and zygosities had no
      influence on balance or peak pressure. Genetic factors moderately influenced
      postural balance, but not peak pressure. The current study is an asset to
      identify and manage influential factors in these variables for female twins.

PMID- 25394474
TI  - Photodynamic therapy as a novel treatment for halitosis in adolescents: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Halitosis is a common problem that affects a large portion of the
      population worldwide. The origin of this condition is oral in 90% and systemic in
      10% of cases. The unpleasant odor is mainly the result of volatile sulfur
      compounds produced by Gram-negative bacteria. However, it has recently been found
      that anaerobic Gram-positive bacteria also produce hydrogen sulfide (H2S) in the
      presence of amino acids, such as cysteine. Light, both with and without the use
      of chemical agents, has been used to induce therapeutic and antimicrobial
      effects. In photodynamic therapy, the antimicrobial effect is confined to areas
      covered by photosensitizing dye. The aim of the present study is to evaluate the
      antimicrobial effect of photodynamic therapy on halitosis in adolescents through
      the analysis of volatile sulfur compounds measured using gas chromatography and
      microbiological analysis of coated tongue. METHODS/DESIGN: A quantitative
      clinical trial will be carried out involving 60 adolescents randomly divided into
      the following groups: group 1 will receive treatment with a tongue scraper, group
      2 will receive photodynamic therapy applied to the posterior two-thirds of the
      dorsum of the tongue, and group 3 will receive combined treatment (tongue scraper
      and photodynamic therapy). Gas chromatography (OralChromaTM) and microbiological
      analysis will be used for the diagnosis of halitosis at the beginning of the
      study. Post-treatment evaluations will be conducted at one hour and 24 hours
      after treatment. The statistical analysis will include the Shapiro-Wilk test for
      the determination of the distribution of the data. If normal distribution is
      demonstrated, analysis of variance followed by Tukey's test will be used to
      compare groups. The Kruskal-Wallis test followed by the Student-Newman-Keuls test
      will be used for data with non-normal distribution. Either the paired t-test or
      the Wilcoxon test will be used to compare data before and after treatment,
      depending on the distribution of the data. DISCUSSION: The results of this trial
      will determine the efficacy of using photodynamic therapy alone or in combination
      with a tongue scraper to treat bad breath in adolescents. TRIAL REGISTRATION: The
      protocol for this study was registered with Clinical Trials (registration number
      NCT02007993) on 10 December 2013.

PMID- 25394476
TI  - Penetration of silver nanoparticles into porcine skin ex vivo using fluorescence
      lifetime imaging microscopy, Raman microscopy, and surface-enhanced Raman
      scattering microscopy.
AB  - In order to investigate the penetration depth of silver nanoparticles (Ag NPs)
      inside the skin, porcine ears treated with Ag NPs are measured by two-photon
      tomography with a fluorescence lifetime imaging microscopy (TPT-FLIM) technique,
      confocal Raman microscopy (CRM), and surface-enhanced Raman scattering (SERS)
      microscopy. Ag NPs are coated with poly-N-vinylpyrrolidone and dispersed in pure
      water solutions. After the application of Ag NPs, porcine ears are stored in the
      incubator for 24 h at a temperature of 37 degrees C. The TPT-FLIM measurement
      results show a dramatic decrease of the Ag NPs' signal intensity from the skin
      surface to a depth of 4 MUm. Below 4 MUm, the Ag NPs' signal continues to
      decline, having completely disappeared at 12 to 14 MUm depth. CRM shows that the
      penetration depth of Ag NPs is 11.1 +/- 2.1 MUm. The penetration depth measured
      with a highly sensitive SERS microscopy reaches 15.6 +/- 8.3 MUm. Several results
      obtained with SERS show that the penetration depth of Ag NPs can exceed the
      stratum corneum (SC) thickness, which can be explained by both penetration of
      trace amounts of Ag NPs through the SC barrier and by the measurements inside the
      hair follicle, which cannot be excluded in the experiment.

PMID- 25394477
TI  - A longitudinal twin study of cluster A personality disorders.
AB  - BACKGROUND: While cluster A personality disorders (PDs) have been shown to be
      moderately heritable, we know little about the temporal stability of these
      genetic risk factors. METHOD: Paranoid PD (PPD) and schizotypal PD (STPD) were
      assessed using the Structured Interview for DSM-IV Personality in 2793 young
      adult twins from the Norwegian Institute of Public Health Twin Panel at wave 1
      and 2282 twins on average 10 years later at wave 2. Using the program Mx, we
      fitted a longitudinal latent factor model using the number of endorsed criteria
      for PPD and STPD. RESULTS: The stability over time of the criteria counts for PPD
      and STPD, estimated as polychoric correlations, were +0.34 and +0.40,
      respectively. The best-fit longitudinal model included only additive genetic and
      individual-specific environmental factors with parameter estimates constrained to
      equality across the two waves. The cross-wave genetic and individual-specific
      environmental correlations for a latent cluster A factor were estimated to equal
      +1.00 and +0.13, respectively. The cross-time correlations for genetic and
      environmental effects specific to the individual PDs were estimated at +1.00 and
      +0.16-0.20, respectively. We found that 68% and 71% of the temporal stability of
      PPD and STPD derived, respectively, from the effect of genetic factors.
      CONCLUSION: Shared genetic risk factors for two of the cluster A PDs are highly
      stable in adults over a 10-year period while environmental risk factors are
      relatively transient. Over two-thirds of the long-term stability of the common
      cluster A PD liability can be attributed to genetic influences.

PMID- 25394478
TI  - Effects of Tet-mediated oxidation products of 5-methylcytosine on DNA
      transcription in vitro and in mammalian cells.
AB  - 5-methylcytosine (5-mC) is a well-characterized epigenetic regulator in mammals.
      Recent studies showed that Ten-eleven translocation (Tet) proteins can catalyze
      the stepwise oxidation of 5-mC to produce 5-hydroxymethylcytosine (5-HmC), 5
      formylcytosine (5-FoC) and 5-carboxylcytosine (5-CaC). The exciting discovery of
      these novel cytosine modifications has stimulated substantial research interests
      about their roles in epigenetic regulation. Here we systematically examined the
      effects of the oxidized 5-mC derivatives on the efficiency and fidelity of DNA
      transcription using a recently developed competitive transcription and adduct
      bypass assay. Our results showed that, when located on the transcribed strand, 5
      FoC and 5-CaC exhibited marginal mutagenic and modest inhibitory effects on DNA
      transcription mediated by single-subunit T7 RNA polymerase or multi-subunit human
      RNA polymerase II in vitro and in human cells. 5-HmC displayed relatively milder
      blocking effects on transcription, and no mutant transcript could be detectable
      for 5-HmC in vitro or in cells. The lack of considerable mutagenic effects of the
      oxidized 5-mC derivatives on transcription was in agreement with their functions
      in epigenetic regulation. The modest blocking effects on transcription suggested
      that 5-FoC and 5-CaC may function in transcriptional regulation. These findings
      provided new evidence for the potential functional interplay between cytosine
      methylation status and transcription. 

PMID- 25394479
TI  - A gene therapy induced emphysema model and the protective role of stem cells.
AB  - BACKGROUND: Chronic obstructive pulmonary disease presents with two different
      phenotypes: chronic bronchitis and emphysema with parenchymal destruction.
      Decreased expression of vascular endothelial growth factor and increased
      endothelial cell apoptosis are considered major factors for emphysema. Stem cells
      have the ability of vascular regeneration and function as a repair mechanism for
      the damaged endothelial cells. Currently, minimally invasive interventional
      procedures such as placement of valves, bio-foam or coils are performed in order
      to improve the disturbed mechanical function in emphysema patients. However,
      these procedures cannot restore functional lung tissue. Additionally stem cell
      instillation into the parenchyma has been used in clinical studies aiming to
      improve overall respiratory function and quality of life. METHODS: In our current
      experiment we induced emphysema with a DDMC non-viral vector in BALBC mice and
      simultaneously instilled stem cells testing the hyposthesis that they might have
      a protective role against the development of emphysema. The mice were divided
      into four groups: a) control, b) 50.000 cells, c) 75.000 and d) 100.000 cells.
      RESULTS: Lung pathological findings revealed that all treatment groups had less
      damage compared to the control group. Additionally, we observed that emphysema
      lesions were less around vessels in an area of 10 MUm. CONCLUSIONS: Our findings
      indicate that stem cell instillation can have a regenerative role if applied upon
      a tissue scaffold with vessel around. VIRTUAL SLIDES: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_195.

PMID- 25394480
TI  - A novel serine hydroxymethyltransferase from Arthrobacter nicotianae:
      characterization and improving catalytic efficiency by rational design.
AB  - BACKGROUND: Serine hydroxymethyltransferase (SHMT) is the key enzyme in L-serine
      enzymatic production, suggesting the importance of obtaining a SHMT with high
      activity. RESULTS: Here, a novel SHMT gene, glyA, was obtained through degenerate
      oligonucleotide-primed PCR and encoded a novel SHMT with 54.3% similarity to the
      known SHMT from Escherichia coli. The obtained protein AnSHMT showed the optimal
      activity at 40  degrees C and pH 7.5, and was more stable in weakly alkali
      conditions (pH 6.5-8.5) than Hyphomicrobium methylovorum's SHMT (pH 6.0-7.5), In
      order to improve the catalytic efficiency of the wild type, the site-directed
      mutagenesis based on sequences alignment and bioinformatics prediction, was used
      and the catalytic efficiency of the mutant I249L was found to be 2.78-fold higher
      than that of the wild-type, with the replacement of isoleucine by leucine at the
      249 position. CONCLUSIONS: This research provides useful information about the
      interesting site, and the application of DOP-PCR in cloning a novel glyA gene.

PMID- 25394482
TI  - Explaining why simple liquids are quasi-universal.
AB  - It has been known for a long time that many simple liquids have surprisingly
      similar structure as quantified, for example, by the radial distribution
      function. A much more recent realization is that the dynamics are also very
      similar for a number of systems with quite different pair potentials. Systems
      with such non-trivial similarities are generally referred to as 'quasi
      universal'. From the fact that the exponentially repulsive pair potential has
      strong virial potential-energy correlations in the low-temperature part of its
      thermodynamic phase diagram, we here show that a liquid is quasi-universal if its
      pair potential can be written approximately as a sum of exponential terms with
      numerically large prefactors. Based on evidence from the literature we moreover
      conjecture the converse, that is, that quasi-universality only applies for
      systems with this property. 

PMID- 25394481
TI  - Heat shock protein 72 suppresses apoptosis by increasing the stability of X
      linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury.
AB  - X-linked inhibitor of apoptosis protein (XIAP) negatively regulates apoptotic
      pathways at a post-mitochondrial level. XIAP functions by directly binding and
      inhibiting activation of specific caspases. Upon apoptotic stimuli, mitochondrial
      second mitochondria-derived activator of caspases (Smac)/direct IAP-binding
      protein with low PI (Diablo) is released into the cytosol, which results in
      displacement of XIAP from caspases. Heat shock protein 72 (HSP72), an anti
      apoptotic protein, prevents mitochondrial injury resulting from acute renal
      ischemia/reperfusion (I/R), its role in Smac/Diablo and XIAP signaling remains to
      be elucidated. In the present study, the hypothesis that HSP72 prevents XIAP
      degradation in vivo and in vitro was assessed. To this purpose, a rat model of
      I/R injury was used to investigate the renoprotective role of HSP72 by treatment
      with geranylgeranylacetone (GGA), a specific inducer of HSP72. The mechanism of
      the cytoprotective properties of HSP72 was also investigated in vitro using
      adenovirus-mediated overexpression of HSP72 in adenosine triphosphate (ATP)
      depleted human kidney 2 (HK-2) cells. Pre-conditioning rats with GGA attenuated
      renal tubular cell damage, reduced cell apoptosis, preserved XIAP protein content
      and improved renal function following I/R injury. An in vitro study was performed
      in which cells were transiently exposed to 5 mM sodium cyanide in a glucose-free
      medium in order to induce apoptosis. Compared with the control, overexpression of
      HSP72 inhibited Smac/Diablo release from the mitochondria and increased levels of
      XIAP and pro-caspase 3 in ATP-depleted HK-2 cells. In addition, HSP72 interacted
      with Smac/Diablo. The present data demonstrates that HSP72 preserves renal
      function in I/R injury through its anti-apoptotic effects, which act by
      suppressing mitochondrial Smac/Diablo release and preserving XIAP protein
      content.

PMID- 25394483
TI  - Kazinol C from Broussonetia kazinoki activates AMP-activated protein kinase to
      induce antitumorigenic effects in HT-29 colon cancer cells.
AB  - Kazinol C is a 1,3-diphenylpropane, obtained from Broussonetia kazinoki, that has
      been employed in folk medicine as an edema suppressant. It exerts beneficial
      effects in oxidative stress-related diseases, such as cancer. However, the
      molecular mechanism involved in the anticancer effects remains to be determined.
      AMP-activated protein kinase (AMPK) has emerged as a possible anticancer target
      molecule. The present study investigated the effect of kazinol C on AMPK
      activation as well as subsequent HT-29 colon cancer cell viability, apoptosis and
      migration. Kazinol C markedly induced AMPK phosphorylation and significantly
      attenuated HT-29 colon cancer cell growth and viability. Compound C, as a well
      known AMPK inhibitor, blocked the kazinol C-induced cell death, and stable
      transduction of dominant-negative (DN) AMPK in colon cancer cells also inhibited
      kazinol C-induced cell apoptosis. In addition, kazinol C inhibited HT-29 cell
      migration and anchorage-independent growth. AMPK inhibition using stable
      transduction with DN AMPK significantly abrogated the kazinol C-induced
      inhibition of cancer cell migration. Thus, AMPK is a critical and novel regulator
      of kazinol C-mediated cancer cell apoptosis and inhibition of migration,
      suggesting that AMPK is a prime cancer target.

PMID- 25394484
TI  - Cloning of the transketolase gene from erythritol-producing yeast Candida
      magnoliae.
AB  - The entire nucleotide sequence of the TKL1 gene encoding transketolase (TKL) in
      an erythritolproducing yeast of Candida magnoliae was determined by degenerate
      polymerase chain reaction and genome walking. Sequence analysis revealed an open
      reading frame of C. magnoliae TKL1 (CmTKL1) that spans 2,088 bp and encodes 696
      amino acids, sharing 61.7% amino acid identity to Kluyveromyces lactis TKL.
      Functional analysis showed that CmTKL1 complemented a Saccharomyces cerevisiae
      tkl1 tkl2 double mutant for growth in the absence of aromatic amino acids and
      restored transketolase activity in this mutant. An enzyme activity assay and RT
      PCR revealed that the expression of CmTKL1 is induced by fructose, H2O2, and KCl.
      The GenBank accession number for C. magnoliae TKL1 is KF751756.

PMID- 25394485
TI  - Cdc42 expression in cervical cancer and its effects on cervical tumor invasion
      and migration.
AB  - The aim of the present study was to examine Cdc42 expression in cervical cancer
      and explore its effects on invasion and migration capability of cervical cancer
      cells. Immunohistochemistry was used to detect Cdc42 expression in normal
      cervical tissues as well as CIN I or below, CIN II or above, and cervical cancer
      tissues. Western blot analysis was used to explore Cdc42 expression in normal
      cervical cell line Crl-2614 and cervical cancer cell line HeLa. Plasmids of
      constitutively active Cdc42 (Cdc42 CA), wild-type Cdc42 (Cdc42 WT) and dominant
      negative Cdc42 (Cdc42 DN) were transfected, respectively, into HeLa cells to
      investigate the impacts of Cdc42 on migration and invasion of cervical cancer
      cells using Transwell and on cytoskeleton microfilaments using confocal
      microscopy after immunofluorescence staining. Cdc42 expression was gradually
      increased in the order of cervical tissues with CIN I or below, CIN II or above
      and cancer, showing significant difference (P<0.05), and was significantly higher
      in HeLa cells than in Crl-2614 cells (P<0.05). Migration ability of HeLa cells
      transfected with Cdc42 CA was significantly higher than that of non-transfected,
      as well as Cdc42 WT- or Cdc42 DN-transfected HeLa cells (P<0.05). Overexpression
      of Cdc42 CA can promote filopodia formation in HeLa cells. We concluded that
      Cdc42 overexpression significantly improved the ability of cervical cancer cells
      to migrate possibly due to improved pseudopodia formation. 

PMID- 25394486
TI  - Oligomeric Abeta-induced synaptic dysfunction in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a devastating disease characterized by synaptic and
      neuronal loss in the elderly. Compelling evidence suggests that soluble amyloid
      beta peptide (Abeta) oligomers induce synaptic loss in AD. Abeta-induced synaptic
      dysfunction is dependent on overstimulation of N-methyl-D-aspartate receptors
      (NMDARs) resulting in aberrant activation of redox-mediated events as well as
      elevation of cytoplasmic Ca2+, which in turn triggers downstream pathways
      involving phospho-tau (p-tau), caspases, Cdk5/dynamin-related protein 1 (Drp1),
      calcineurin/PP2B, PP2A, Gsk-3beta, Fyn, cofilin, and CaMKII and causes
      endocytosis of AMPA receptors (AMPARs) as well as NMDARs. Dysfunction in these
      pathways leads to mitochondrial dysfunction, bioenergetic compromise and
      consequent synaptic dysfunction and loss, impaired long-term potentiation (LTP),
      and cognitive decline. Evidence also suggests that Abeta may, at least in part,
      mediate these events by causing an aberrant rise in extrasynaptic glutamate
      levels by inhibiting glutamate uptake or triggering glutamate release from glial
      cells. Consequent extrasynaptic NMDAR (eNMDAR) overstimulation then results in
      synaptic dysfunction via the aforementioned pathways. Consistent with this model
      of Abeta-induced synaptic loss, Abeta synaptic toxicity can be partially
      ameliorated by the NMDAR antagonists (such as memantine and NitroMemantine). PSD
      95, an important scaffolding protein that regulates synaptic distribution and
      activity of both NMDA and AMPA receptors, is also functionally disrupted by
      Abeta. PSD-95 dysregulation is likely an important intermediate step in the
      pathological cascade of events caused by Abeta. In summary, Abeta-induced
      synaptic dysfunction is a complicated process involving multiple pathways,
      components and biological events, and their underlying mechanisms, albeit as yet
      incompletely understood, may offer hope for new therapeutic avenues. 

PMID- 25394487
TI  - Epo-induced erythroid maturation is dependent on Plcgamma1 signaling.
AB  - Erythropoiesis is a tightly regulated process. Development of red blood cells
      occurs through differentiation of hematopoietic stem cells (HSCs) into more
      committed progenitors and finally into erythrocytes. Binding of erythropoietin
      (Epo) to its receptor (EpoR) is required for erythropoiesis as it promotes
      survival and late maturation of erythroid progenitors. In vivo and in vitro
      studies have highlighted the requirement of EpoR signaling through Janus kinase 2
      (Jak2) tyrosine kinase and Stat5a/b as a central pathway. Here, we demonstrate
      that phospholipase C gamma 1 (Plcgamma1) is activated downstream of EpoR-Jak2
      independently of Stat5. Plcgamma1-deficient pro-erythroblasts and erythroid
      progenitors exhibited strong impairment in differentiation and colony-forming
      potential. In vivo, suppression of Plcgamma1 in immunophenotypically defined HSCs
      (Lin(-)Sca1(+)KIT(+)CD48(-)CD150(+)) severely reduced erythroid development. To
      identify Plcgamma1 effector molecules involved in regulation of erythroid
      differentiation, we assessed changes occurring at the global transcriptional and
      DNA methylation level after inactivation of Plcgamma1. The top common downstream
      effector was H2afy2, which encodes for the histone variant macroH2A2 (mH2A2).
      Inactivation of mH2A2 expression recapitulated the effects of Plcgamma1 depletion
      on erythroid maturation. Taken together, our findings identify Plcgamma1 and its
      downstream target mH2A2, as a 'non-canonical' Epo signaling pathway essential for
      erythroid differentiation. 

PMID- 25394488
TI  - MicroRNA-221 inhibits autophagy and promotes heart failure by modulating the
      p27/CDK2/mTOR axis.
AB  - MicroRNAs have emerged as crucial regulators of cardiac homeostasis and
      remodeling in various cardiovascular diseases. We previously demonstrated that
      miR-221 regulated cardiac hypertrophy in vitro. In the present study, we
      demonstrated that the cardiac-specific overexpression of miR-221 in mice evoked
      cardiac dysfunction and heart failure. The lipidated form of microtubule
      associated protein 1 light chain 3 was significantly decreased and sequestosome 1
      was accumulated in cardiac tissues of transgenic (TG) mice, indicating that
      autophagy was impaired. Overexpression of miR-221 in vitro reduced autophagic
      flux through inhibiting autophagic vesicle formation. Furthermore, mammalian
      target of rapamycin (mTOR) was activated by miR-221, both in vivo and in vitro.
      The inactivation of mTOR abolished the miR-221-induced inhibition of autophagy
      and cardiac remodeling. Our previous study has demonstrated that cyclin-dependent
      kinase (CDK) inhibitor p27 was a direct target of miR-221 in cardiomyocytes.
      Consistently, the expression of p27 was markedly suppressed in the myocardia of
      TG mice. Knockdown of p27 by siRNAs was sufficient to mimic the effects of miR
      221 overexpression on mTOR activation and autophagy inhibition, whereas
      overexpression of p27 rescued miR-221-induced autophagic flux impairment.
      Inhibition of CDK2 restored the impaired autophagic flux and rescued the cardiac
      remodeling induced by either p27 knockdown or miR-221 overexpression. These
      findings reveal that miR-221 is an important regulator of autophagy balance and
      cardiac remodeling by modulating the p27/CDK2/mTOR axis, and implicate miR-221 as
      a therapeutic target in heart failure. 

PMID- 25394489
TI  - PTEN induces apoptosis and cavitation via HIF-2-dependent Bnip3 upregulation
      during epithelial lumen formation.
AB  - The tumor suppressor phosphatase and tensin homolog (PTEN) dephosphorylates PIP3
      and antagonizes the prosurvival PI3K-Akt pathway. Targeted deletion of PTEN in
      mice led to early embryonic lethality. To elucidate its role in embryonic
      epithelial morphogenesis and the underlying mechanisms, we used embryonic stem
      cell-derived embryoid body (EB), an epithelial cyst structurally similar to the
      periimplantation embryo. PTEN is upregulated during EB morphogenesis in parallel
      with apoptosis of core cells, which mediates EB cavitation. Genetic ablation of
      PTEN causes Akt overactivation, apoptosis resistance and cavitation blockade.
      However, rescue experiments using mutant PTEN and pharmacological inhibition of
      Akt suggest that the phosphatase activity of PTEN and Akt are not involved in
      apoptosis-mediated cavitation. Instead, hypoxia-induced upregulation of Bnip3, a
      proapoptotic BH3-only protein, mediates PTEN-dependent apoptosis and cavitation.
      PTEN inactivation inhibits hypoxia- and reactive oxygen species-induced Bnip3
      elevation. Overexpression of Bnip3 in PTEN-null EBs rescues apoptosis of the core
      cells. Mechanistically, suppression of Bnip3 following PTEN loss is likely due to
      reduction of hypoxia-inducible factor-2alpha (HIF-2alpha) because forced
      expression of an oxygen-stable HIF-2alpha mutant rescues Bnip3 expression and
      apoptosis. Lastly, we show that HIF-2alpha is upregulated by PTEN at both
      transcriptional and posttranscriptional levels. Ablation of prolyl hydroxylase
      domain-containing protein 2 (PHD2) in normal EBs or inhibition of PHD activities
      in PTEN-null EBs stabilizes HIF-2alpha and induces Bnip3 and caspase-3
      activation. Altogether, these results suggest that PTEN is required for apoptosis
      mediated cavitation during epithelial morphogenesis by regulating the expression
      of HIF-2alpha and Bnip3. 

PMID- 25394490
TI  - GSK-3beta dysregulation contributes to parkinson's-like pathophysiology with
      associated region-specific phosphorylation and accumulation of tau and alpha
      synuclein.
AB  - Aberrant posttranslational modifications (PTMs) of proteins, namely
      phosphorylation, induce abnormalities in the biological properties of recipient
      proteins, underlying neurological diseases including Parkinson's disease (PD).
      Genome-wide studies link genes encoding alpha-synuclein (alpha-Syn) and Tau as
      two of the most important in the genesis of PD. Although several kinases are
      known to phosphorylate alpha-Syn and Tau, we focused our analysis on GSK-3beta
      because of its accepted role in phosphorylating Tau and to increasing evidence
      supporting a strong biophysical relationship between alpha-Syn and Tau in PD.
      Therefore, we investigated transgenic mice, which express a point mutant (S9A) of
      human GSK-3beta. GSK-3beta-S9A is capable of activation through endogenous
      natural signaling events, yet is unable to become inactivated through
      phosphorylation at serine-9. We used behavioral, biochemical, and in vitro
      analysis to assess the contributions of GSK-3beta to both alpha-Syn and Tau
      phosphorylation. Behavioral studies revealed progressive age-dependent impairment
      of motor function, accompanied by loss of tyrosine hydroxylase-positive (TH+ DA
      neurons) neurons and dopamine production in the oldest age group. Magnetic
      resonance imaging revealed deterioration of the substantia nigra in aged mice, a
      characteristic feature of PD patients. At the molecular level, kinase-active p
      GSK-3beta-Y216 was seen at all ages throughout the brain, yet elevated levels of
      p-alpha-Syn-S129 and p-Tau (S396/404) were found to increase with age exclusively
      in TH+ DA-neurons of the midbrain. p-GSK-3beta-Y216 colocalized with p-Tau and p
      alpha-Syn-S129. In vitro kinase assays showed that recombinant human GSK-3beta
      directly phosphorylated alpha-Syn at a single site, Ser129, in addition to its
      known ability to phosphorylate Tau. Moreover, alpha-Syn and Tau together
      cooperated with one another to increase the magnitude or rate of phosphorylation
      of the other by GSK-3beta. Together, these data establish a novel upstream role
      for GSK-3beta as one of several kinases associated with PTMs of key proteins
      known to be causal in PD. 

PMID- 25394491
TI  - Neurocognitive and familial moderators of psychiatric risk in velocardiofacial
      (22q11.2 deletion) syndrome: a longitudinal study.
AB  - BACKGROUND: Although risk for psychosis in velocardiofacial (22q11.2 deletion)
      syndrome (VCFS) is well established, the cognitive and familial factors that
      moderate that risk are poorly understood. METHOD: A total of 75 youth with VCFS
      were assessed at three time points, at 3-year intervals. Time 1 (T1) psychiatric
      risk was assessed with the Behavior Assessment System for Children (BASC). Data
      reduction of BASC scores yielded avoidance-anxiety and dysregulation factors.
      Time 2 (T2) neuropsychological and family function and time 3 (T3)
      prodromal/overt psychosis were assessed. Poisson regression models tested
      associations between T3 positive prodromal symptoms/overt psychosis and T1
      psychiatric risk, T2 cognitive and familial factors, and their interactions.
      RESULTS: T1 avoidance-anxiety ratings predicted T3 prodromal/overt psychosis. T2
      verbal learning scores moderated this association, such that individuals with low
      avoidance-anxiety scores and stronger verbal learning skills were the least
      likely to demonstrate prodromal/overt psychosis at T3. Low scores on a T2 visual
      vigilance task also predicted T3 prodromal/overt psychosis, independently of the
      effect of T1 avoidance-anxiety scores. T1 dysregulation scores did not predict T3
      prodromal/overt psychosis in a linear manner. Instead, the association between
      dysregulation and prodromal/overt psychosis was amplified by T2 levels of family
      organization, such that individuals with low dysregulation scores and low family
      organization scores were the most likely to exhibit T3 prodromal/overt psychosis.
      CONCLUSIONS: Significant moderators of psychiatric risk in VCFS include verbal
      learning skills as well as levels of family organization, carrying implications
      for early identification and preventative treatment of youth with VCFS at highest
      risk for psychosis.

PMID- 25394492
TI  - MicroRNA-7 directly targets insulin-like growth factor 1 receptor to inhibit
      cellular growth and glucose metabolism in gliomas.
AB  - BACKGROUND: Recent studies observed that altered energy metabolism has become
      widespread in cancer cells along with other cancer-associated traits that have
      been accepted as hallmarks of cancer. Akt signaling pathway is involved in the
      aerobic glycolysis program. However, mechanisms underlying the regulation of
      aerobic glycolysis and Akt activity in gliomas remain unclear. MicroRNAs are a
      group of small non-coding RNAs that can function as endogenous RNA interference
      to regulate expression of targeted genes. This study was conducted to detect the
      function of miR-7 targeting insulin-like growth factor 1 receptor (IGF-1R), which
      is an upstream regulator of Akt. METHODS: MicroRNA expression data for gliomas
      and normal controls were downloaded from The Cancer Genome Atlas (TCGA) database.
      Quantitative real-time PCR was used to measure the microRNA-7 (miR-7) expression
      level, and Western blot was performed to detect protein expression in U87 and
      U251 cells. Colony formation assay and glycolysis stress test were also
      conducted. Luciferase reporter assay was used to identify the mechanism of IGF-1R
      and miR-7 regulation. RESULTS: miR-7 was downregulated in human glioma tissues
      based on TCGA database. Forced expression of miR-7 or IGF-1R knockdown inhibited
      colony formation and glucose metabolic capabilities of glioma cells in vitro and
      decreased the p-Akt expression level. Bioinformatics analysis results indicated
      that IGF-1R could be a target of miR-7. Western blot and luciferase reporter
      assays showed that miR-7 modulated IGF-1R expression by directly targeting the
      binding site within the 3'-untranslated region. CONCLUSIONS: This study provides
      the first evidence that miR-7 inhibits cellular growth and glucose metabolism in
      gliomas, at least partially, by regulating the IGF-1R/Akt signaling pathway.
      Therefore, miR-7 is a promising molecular drug for glioma treatment. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_211.

PMID- 25394493
TI  - Metal-organic framework based highly selective fluorescence turn-on probe for
      hydrogen sulphide.
AB  - Hydrogen sulphide (H2S) is known to play a vital role in human physiology and
      pathology which stimulated interest in understanding complex behaviour of H2S.
      Discerning the pathways of H2S production and its mode of action is still a
      challenge owing to its volatile and reactive nature. Herein we report azide
      functionalized metal-organic framework (MOF) as a selective turn-on fluorescent
      probe for H2S detection. The MOF shows highly selective and fast response towards
      H2S even in presence of other relevant biomolecules. Low cytotoxicity and H2S
      detection in live cells, demonstrate the potential of MOF towards monitoring H2S
      chemistry in biological system. To the best of our knowledge this is the first
      example of MOF that exhibit fast and highly selective fluorescence turn-on
      response towards H2S under physiological conditions. 

PMID- 25394494
TI  - A comparison of commercially-available automated and manual extraction kits for
      the isolation of total RNA from small tissue samples.
AB  - BACKGROUND: This study compared the performance of five commercially available
      kits in extracting total RNA from small eukaryotic tissue samples (<15 mg). Total
      RNA was isolated from fathead minnow (Pimephales promelas) tissues (spleen,
      blood, kidney, embryo, and larvae) using the Qiagen RNeasy(r) Plus Mini, Qiagen
      RNeasy(r) Plus Universal, Promega Maxwell(r) 16 LEV simplyRNA, Ambion MagMAXTM-96
      and Promega SimplyRNA HT kits. Kit performance was evaluated via measures of RNA
      quantity (e.g., total RNA amount) and quality (e.g., ratio of absorbance at 260
      and 280 nm, RNA integrity number (RIN), presence of gDNA). RESULTS: With the
      exception of embryos, each kit generally extracted >=5 MUg of total RNA from each
      sample. With regard to RNA quality, the RINs of RNA samples isolated via the Plus
      Mini and Maxwell(r) 16 kits were consistently higher than those of samples
      extracted via the remaining three kits and for all tissues, these kits produced
      intact RNA with average RIN values >=7. The Plus Universal and SimplyRNA HT kits
      produced moderately degraded (RIN values <7, but >=5), while the RNA recovered
      via the MagMAXTM kit tended to exhibit a high degree of degradation (RIN values
      <5). CONCLUSIONS: Each kit was generally capable of extracting the amount of RNA
      required for most downstream gene expression applications suggesting that RNA
      yield is unlikely to be a limiting factor for any of the kits evaluated. However,
      differences in the quality of RNA extracted via each of the kits indicate that
      these kits may differ in their ability to yield RNA acceptable for some
      applications. Overall, the findings of this study demonstrate that there are
      practical differences between commercially available RNA extraction kits that
      should be taken into account when selecting extraction methods to be used for
      isolating RNA designated for gene expression analysis.

PMID- 25394495
TI  - Docosahexanoic acid modifies low-density lipoprotein receptor abundance in HepG2
      cells via suppression of the LXRalpha-Idol pathway.
AB  - As a daily supplement, omega-3 fatty acid is confirmed to be of benefit in
      hypertriglyceridemia. However, the effect of omega-3 fatty acids on the low
      density lipoprotein cholesterol (LDL-C) metabolism remains a controversial issue.
      In this study, we focused on the regulatory effect of docosahexanoic acid (DHA),
      one type of omega-3 fatty acid, exerted on the LDL receptor (LDLR), a determinant
      regulator of the LDL-C metabolism, and explored the potential mechanism. We
      observed that DHA increased hepatic LDLR protein in the presence of 25
      hydroxycholesterol in HepG2 cells but did not alter the mRNA level. Previous
      studies have identified inducible degrader of the LDLR (Idol) as a novel negative
      post-translational modulator of LDLR and a direct transcriptional target of liver
      X receptor alpha (LXRalpha). Since DHA had no effect on the transcriptional level
      of LDLR, we speculated that the post-transcriptional pathway LXRalpha-Idol
      participated in this regulation. The results reveal that DHA downregulated the
      expression of LXRalpha and Idol in coordination with the upregulation of LDLR
      expression. Multiple mechanisms are involved in the regulation of LDLR by DHA,
      and the suppression of the LXRalpha-Idol pathway is one of these mechanisms.

PMID- 25394496
TI  - Interlaced crystals having a perfect Bravais lattice and complex chemical order
      revealed by real-space crystallography.
AB  - The search for optimal thermoelectric materials aims for structures in which the
      crystalline order is disrupted to lower the thermal conductivity without
      degradation of the electron conductivity. Here we report the synthesis and
      characterisation of ternary nanoparticles (two cations and one anion) that
      exhibit a new form of crystalline order: an uninterrupted, perfect, global
      Bravais lattice, in which the two cations exhibit a wide array of distinct
      ordering patterns within the cation sublattice, forming interlaced domains and
      phases. Partitioning into domains and phases is not unique; the corresponding
      boundaries have no structural defects or strain and entail no energy cost. We
      call this form of crystalline order 'interlaced crystals' and present the example
      of hexagonal CuInS2. Interlacing is possible in multi-cation tetrahedrally bonded
      compound with an average of two electrons per bond. Interlacing has minimal
      effect on electronic properties, but should strongly reduce phonon transport,
      making interlaced crystals attractive for thermoelectric applications. 

PMID- 25394497
TI  - Flavonoids in Ginkgo biloba fallen leaves induce apoptosis through modulation of
      p53 activation in melanoma cells.
AB  - The aim of the present study was to examine the apoptotic effect of flavonoids in
      methanol extracts of Ginkgo biloba fallen leaves (MEGFL) on melanoma cells.
      Ginkgo biloba is a deciduous castle chaplain and its leaves include various types
      of flavonoids such as flavonol-O-glycosides. Ginkgo biloba is known to have
      therapeutic properties against a number of diseases such as cerebrovascular
      diseases, blood circulation disease and hypertension. In the present study MEGFL
      exhibited a higher cytotoxic effect on melanoma cells than Ginkgo biloba leaves
      (MEGL). It was also found that MEGFL induced apoptotic cell death which was
      characterized by DNA fragmentation. During the cell death process following
      treatment with MEGFL, the expression of a variety of death-associated proteins
      including p53, caspase-3, caspase-9, cytochrome c and Bax were analyzed in the
      cytosol of melanoma cells. MEGFL significantly increased the expression levels of
      caspase-3, caspase-9 and p53 in a dose-dependent manner. Our results indicate
      that MEGFL induced apoptotic cell death by increasing the expression of cell
      death-associated proteins in melanoma cells.

PMID- 25394498
TI  - An unusual cause of dysphagia: "DISHphagia".
AB  - Progressive dysphagia and dyspnoea presenting after major neck trauma can
      occasionally be secondary to post-traumatic inflammation and mass effect
      associated with a calcified osteophytic anterior longitudinal ligament, a
      frequent finding in diffuse idiopathic skeletal hyperostosis, though rarely
      enough to cause such symptoms. In these circumstances, surgical decompression may
      prove effective. 

PMID- 25394499
TI  - Dermoscopy of Naevus-associated Melanomas.
AB  - In order to determine dermoscopic parameters, a case-control test set of naevus
      associated melanomas vs de novo melanomas paired by Breslow thickness and
      histopathological subtype was analysed by 2 blinded experienced dermoscopists,
      according to presence of naevus, pattern analysis and ABCD dermoscopy score. The
      ability to identify naevus-associated melanomas by pattern analysis was low for
      both blinded dermoscopists (kappa < 0.2). Dermoscopy features associated with
      naevus-associated melanomas were: presence of negative pigment network (OR 9.915,
      CI 95% 2.182-45.049), globules (OR 2.383, CI 95% 1.15-4.95) and streaks (OR
      2.439, CI 95% 1.271-4.680). In contrast, the presence of blue-white veil was
      related to absence of associated naevus (OR 0.520, CI 95% 0.273-0.991). With the
      results obtained, 2 different algorithms were proposed. The use of the proposed
      algorithms could help raise awareness of naevus-associated melanomas and avoid
      the possibility of incorrectly diagnosing a naevus-associated melanoma if partial
      biopsies are performed.

PMID- 25394500
TI  - Septic arthritis caused by Brucella melitensis in urban Shenzhen, China: a case
      report.
AB  - INTRODUCTION: Brucellosis is a systemic infectious disease which is still a
      challenging medical problem in rural areas such as northern China. It rarely
      occurs in urban areas such as Shenzhen in southern China. Osteoarticular
      involvements are frequently seen in brucellosis, and rarely is arthritis the only
      clinical presentation. We report a case of hip septic arthritis caused by
      Brucella melitensis in an urban area of Shenzhen, China. CASE PRESENTATION: A 29
      year-old Chinese woman, Han ethnical group presented to our hospital with left
      hip pain persisting for one month. She had a history of contact with goats one
      month before admission. Her clinical examination showed marked tenderness and
      limited movement of her left hip. Further imaging showed effusion of her left hip
      joint. Inflammatory markers including erythrocyte sedimentation rate (ESR) and c
      reactive protein (CRP) were raised. Our clinical diagnosis was septic arthritis
      of the left hip. A left hip arthroscopy was performed and the culture was
      positive for Brucella melitensis. She returned to normal activity after
      completing a standard antibiotic regimen, including gentamicin at 120mg daily for
      2 weeks, doxycycline at 100mg daily and rifampicin at 450mg for a total of 12
      weeks. CONCLUSIONS: Brucellosis is endemic in some rural areas of China, but rare
      in urban areas such as Shenzhen in southern China. However, more cases will be
      expected in urban areas due to increasing migration within China. Physicians
      should consider brucellosis as one of the differential diagnosis of arthritis.
      Early surgical intervention is recommended to prevent further joint destruction.

PMID- 25394501
TI  - Winter is coming: vaccine negotiations should be concluded swiftly.

PMID- 25394502
TI  - Economic evaluation of nebulized magnesium sulphate in acute severe asthma in
      children.
AB  - OBJECTIVES: The aim of this study was to estimate the cost-effectiveness of
      nebulized magnesium sulphate (MgSO4) in acute asthma in children from the
      perspective of the UK National Health Service and personal social services.
      METHODS: An economic evaluation was conducted based on evidence from a randomized
      placebo controlled multi-center trial of nebulized MgSO4 in severe acute asthma
      in children. Participants comprised 508 children aged 2-16 years presenting to an
      emergency department or a children's assessment unit with severe acute asthma
      across thirty hospitals in the United Kingdom. Children were randomly allocated
      to receive nebulized salbutamol and ipratropium bromide mixed with either 2.5 ml
      of isotonic MgSO4 or 2.5 ml of isotonic saline on three occasions at 20-min
      intervals. Cost-effectiveness outcomes were constructed around the Yung Asthma
      Severity Score (ASS) after 60 min of treatment; whilst cost-utility outcomes were
      constructed around the quality-adjusted life-year (QALY) metric. The
      nonparametric bootstrap method was used to present cost-effectiveness
      acceptability curves at alternative cost-effectiveness thresholds for either: (i)
      a unit reduction in ASS; or (ii) an additional QALY. RESULTS: MgSO4 had a 75.1
      percent probability of being cost-effective at a GBP 1,000 (EUR 1,148) per unit
      decrement in ASS threshold, an 88.0 percent probability of being more effective
      (in terms of reducing the ASS) and a 36.6 percent probability of being less
      costly. MgSO4 also had a 67.6 percent probability of being cost-effective at a
      GBP 20,000 (EUR 22,957) per QALY gained threshold, an 8.5 percent probability of
      being more effective (in terms of generating increased QALYs) and a 69.1 percent
      probability of being less costly. Sensitivity analyses showed that the results of
      the economic evaluation were particularly sensitive to the methods used for QALY
      estimation. CONCLUSIONS: The probability of cost-effectiveness of nebulized
      isotonic MgSO4, given as an adjuvant to standard treatment of severe acute asthma
      in children, is less than 70 percent across accepted cost-effectiveness
      thresholds for an additional QALY.

PMID- 25394503
TI  - Novel and enhanced anti-melanoma DNA vaccine targeting the tyrosinase protein
      inhibits myeloid-derived suppressor cells and tumor growth in a syngeneic
      prophylactic and therapeutic murine model.
AB  - Melanoma is the most deadly type of skin cancer, constituting annually ~ 75% of
      all cutaneous cancer-related deaths due to metastatic spread. Currently, because
      of metastatic spread, there are no effective treatment options for late-stage
      metastatic melanoma patients. Studies over the past two decades have provided
      insight into several complex molecular mechanisms as to how these malignancies
      evade immunological control, indicating the importance of immune escape or
      suppression for tumor survival. Thus, it is essential to develop innovative
      cancer strategies and address immune obstacles with the goal of generating more
      effective immunotherapies. One important area of study is to further elucidate
      the role and significance of myeloid-derived suppressor cells (MDSCs) in the
      maintenance of the tumor microenvironment. These cells possess a remarkable
      ability to suppress immune responses and, as such, facilitate tumor growth. Thus,
      MDSCs represent an important new target for preventing tumor progression and
      escape from immune control. In this study, we investigated the role of MDSCs in
      immune suppression of T cells in an antigen-specific B16 melanoma murine system
      utilizing a novel synthetic tyrosinase (Tyr) DNA vaccine therapy in both
      prophylactic and therapeutic models. This Tyr vaccine induced a robust and broad
      immune response, including directing CD8 T-cell infiltration into tumor sites.
      The vaccine also reduced the number of MDSCs in the tumor microenvironment
      through the downregulation of monocyte chemoattractant protein 1, interleukin-10,
      CXCL5 and arginase II, factors important for MDSC expansion. This novel synthetic
      DNA vaccine significantly reduced the melanoma tumor burden and increased
      survival in vivo, due likely, in part, to the facilitation of a change in the
      tumor microenvironment through MDSC suppression.

PMID- 25394504
TI  - Knockdown of EGFR inhibits growth and invasion of gastric cancer cells.
AB  - The epidermal growth factor receptor (EGFR) is an oncogenic trans-membranous
      receptor, which is overexpressed in multiple human cancers. However, the role of
      EGFR in gastric cancer (GC) is still elusive. In this study, we aimed to
      investigate the expression and molecular mechanisms of EGFR in GC cells. Forty
      cases of GC and the corresponding adjacent non-cancerous tissues (ANCT) were
      collected, and the expression of EGFR was assessed using immunohistochemistry in
      biopsy samples. Furthermore, EGFR signaling was blocked by constructed
      recombinant small hairpin RNA lentiviral vector (Lv-shRAGE) used to transfect
      into human GC SGC-7901 cells. The expression of AKT, proliferating cell nuclear
      antigen (PCNA) and matrix metallopeptidase-9 (MMP-9) was detected by real-time
      PCR and western blotting assays. Cell proliferative activities and invasive
      capability were, respectively, determined by MTT (3-[4,5-dimethylthiazol-2-yl]
      2,5 diphenyl tetrazolium bromide) and Transwell assays. Cell apoptosis and cycle
      distribution were analyzed by flow cytometry. EGFR was found highly expressed in
      cancer tissues compared with the ANCT and correlated with lymph node metastases.
      Knockdown of EGFR reduced cell proliferation and invasion of GC with decreased
      expression of AKT, PCNA and MMP-9 and induced cell apoptosis and cycle arrest.
      Upregulation of EGFR expression is associated with lymph node metastases of GC,
      and blockade of EGFR signaling suppresses growth and invasion of GC cells through
      AKT pathway, suggesting that EGFR may represent a potential therapeutic target
      for this aggressive malignancy. 

PMID- 25394506
TI  - Downregulation of Msi1 suppresses the growth of human colon cancer by targeting
      p21cip1.
AB  - Musashi1 (Msi1), a member of the RNA-binding protein (RBP) family, is highly
      expressed in neural progenitor or stem cells for the maintenance of stemness as
      well as in various cancers. Emerging studies have demonstrated that it regulates
      cell processes by translational activation or suppresses specifically bound mRNA.
      In the present study, we initially reported remarkably increased expression of
      Msi1 in colon cancer tissues compared with adjacent non-tumor tissues. Knockdown
      of Msi1 significantly suppressed the proliferation, colony formation, tumorsphere
      formation and the progression of implanted colon cancers, and induced cell cycle
      attest at G0/G1 phase, along with the upregulated expression of p21(cip1).
      Reporter assays using a chimeric mRNA that combined luciferase and the 3'-UTR of
      p21(cip1) revealed that Msi1 decreased the reporter activity through the specific
      motif. Thus, the current results suggested that downregulation of Msi1 could
      inhibit the growth of colon cancers and Msi1 may be a promising therapeutic
      target molecule for human colon cancers.

PMID- 25394507
TI  - Effect of herbicide combinations on Bt-maize rhizobacterial diversity.
AB  - Reports of herbicide resistance events are proliferating worldwide, leading to
      new cultivation strategies using combinations of pre-emergence and post-emergence
      herbicides. We analyzed the impact during a one-year cultivation cycle of several
      herbicide combinations on the rhizobacterial community of glyphosate-tolerant Bt
      maize and compared them to those of the untreated or glyphosate-treated soils.
      Samples were analyzed using pyrosequencing of the V6 hypervariable region of the
      16S rRNA gene. The sequences obtained were subjected to taxonomic, taxonomy
      independent, and phylogeny-based diversity studies, followed by a statistical
      analysis using principal components analysis and hierarchical clustering with
      jackknife statistical validation. The resilience of the microbial communities was
      analyzed by comparing their relative composition at the end of the cultivation
      cycle. The bacterial communites from soil subjected to a combined treatment with
      mesotrione plus s-metolachlor followed by glyphosate were not statistically
      different from those treated with glyphosate or the untreated ones. The use of
      acetochlor plus terbuthylazine followed by glyphosate, and the use of aclonifen
      plus isoxaflutole followed by mesotrione clearly affected the resilience of their
      corresponding bacterial communities. The treatment with pethoxamid followed by
      glyphosate resulted in an intermediate effect. The use of glyphosate alone seems
      to be the less aggressive one for bacterial communities. Should a combined
      treatment be needed, the combination of mesotrione and s-metolachlor shows the
      next best final resilience. Our results show the relevance of comparative
      rhizobacterial community studies when novel combined herbicide treatments are
      deemed necessary to control weed growth.. 

PMID- 25394505
TI  - Measles Edmonston vaccine strain derivatives have potent oncolytic activity
      against osteosarcoma.
AB  - Osteosarcoma (OS) is the most common primary bone tumor affecting children and
      young adults, and development of metastatic disease is associated with poor
      prognosis. The purpose of this study was to evaluate the antitumor efficacy of
      virotherapy with engineered measles virus (MV) vaccine strains in the treatment
      of OS. Cell lines derived from pediatric patients with OS (HOS, MG63, 143B, KHOS
      312H, U2-OS and SJSA1) were infected with MV expressing green fluorescent protein
      (MV-GFP) and MV-expressing sodium iodide symporter (MV-NIS) strains. Viral gene
      expression and cytotoxicity as defined by syncytial formation, cell death and
      eradication of cell monolayers were demonstrated. Findings were correlated with
      in vivo efficacy in subcutaneous, orthotopic (tibial bone) and lung metastatic OS
      xenografts treated with the MV derivative MV-NIS via the intratumoral or
      intravenous route. Following treatment, we observed decrease in tumor growth of
      subcutaneous xenografts (P=0.0374) and prolongation of survival in mice with
      orthotopic (P<0.0001) and pulmonary metastatic OS tumors (P=0.0207). Expression
      of the NIS transgene in MV-NIS infected tumors allowed for single photon emission
      computed tomography and positron emission tomography-computed tomography imaging
      of virus infected tumors in vivo. Our data support the translational potential of
      MV-based virotherapy approaches in the treatment of recurrent and metastatic OS. 

PMID- 25394508
TI  - Molecular cloning and characterization of a novel cold-adapted family VIII
      esterase from a biogas slurry metagenomic library.
AB  - A novel esterase gene, est01, was successfully unearthed from a biogas digester
      microbiota metagenomic library. The 1,194 bp est01 gene encodes a protein of
      44,804 Da (designated Est01). The amino acid sequence of Est01 shows only
      moderate (33%) identity to a lipase/ esterase. Phylogenetic analysis and
      biochemical characterization confirmed that Est01 is a new member of family VIII
      esterases. The purified Est01 from recombinant Escherichia coli BL21 (DE3) showed
      high hydrolytic activity against short-chain fatty acid esters, suggesting that
      it is a typical carboxylesterase rather than a lipase. Furthermore, the Est01 was
      even active at 10 degrees C (43% activity remained), with the optimal temperature
      at 20 degrees C, and had a broad pH range from 5.0 to 10.0, with the optimal pH
      of 8.0. These properties suggest that Est01 is a cold-adaptive esterase and could
      have good potential for low-temperature hydrolysis application. 

PMID- 25394509
TI  - Genome of betaproteobacterium Caenimonas sp. strain SL110 contains a coenzyme
      F420 biosynthesis gene cluster.
AB  - To probe the genomic properties of microbes thriving in desert lakes, we
      sequenced the full genome of a betaproteobacterial strain (SL110) belonging to
      the understudied genus Caenimonas of the family Comamonadaceae. This strain was
      isolated from a freshwater lake in the western Gobi Desert, Northern China. Its
      genome contains genes encoding carbon monoxide dehydrogenase, nitrate reductase,
      nitrite reductase, nitric oxide reductase, and sulfur oxidation enzymes,
      highlighting the potentially important contribution of this group of bacteria to
      the cycling of inorganic elements in nature. Unexpectedly, a coenzyme F420
      biosynthesis gene cluster was identified. A further search for F420 biosynthesis
      gene homologs in genomic databases suggests the possible widespread presence of
      F420 biosynthesis gene clusters in proteobacterial genomes. 

PMID- 25394510
TI  - Correlation between Pr1 and Pr2 gene content and virulence in Metarhizium
      anisopliae strains.
AB  - Metarhizium anisopliae is a widely studied model to understand the virulence
      factors that participate in pathogenicity. Proteases such as subtilisin-like
      enzymes (Pr1) and trypsin-like enzymes (Pr2) are considered important factors for
      insect cuticle degradation. In four M. anisopliae strains (798, 6342, 6345, and
      6347), the presence of pr1 and pr2 genes, as well as the enzymatic activity of
      these genes, was correlated with their virulence against two different insect
      pests. The 11 pr1 genes (A, B, C, D, E, F, G, H, I, J, and K) and pr2 gene were
      found in all strains. The activity of individual Pr1 and Pr2 proteases exhibited
      variation in time (24, 48, 72, and 96 h) and in the presence or absence of chitin
      as the inductor. The highest Pr1 enzymatic activity was shown by strain 798 at 48
      h with chitin. The highest Pr2 enzymatic activity was exhibited by the 6342 and
      6347 strains, both grown with chitin at 24 and 48 h, respectively. Highest
      mortality on S. exigua was caused by strain 6342 at 48 h, and strains 6342, 6345,
      and 6347 caused the highest mortality 7 days later. Mortality on Prosapia reached
      30% without variation. The presence of subtilisin and trypsin genes and the
      activity of these proteases in M. anisopliae strains cannot be associated with
      the virulence against the two insect pests. Probably, subtilisin and trypsin
      enzyme production is not a vital factor for pathogenicity, but its contribution
      is important to the pathogenicity process. 

PMID- 25394511
TI  - Effects of volatile solid concentration and mixing ratio on hydrogen production
      by co-digesting molasses wastewater and sewage sludge.
AB  - Co-digesting molasses wastewater and sewage sludge was evaluated for hydrogen
      production by response surface methodology (RSM). Batch experiments in accordance
      with various dilution ratios (40- to 5-fold) and waste mixing composition ratios
      (100:0, 80:20, 60:40, 40:60, 20:80, and 0:100, on a volume basis) were conducted.
      Volatile solid (VS) concentration strongly affected the hydrogen production rate
      and yield compared with the waste mixing ratio. The specific hydrogen production
      rate was predicted to be optimal when the VS concentration ranged from 10 to 12
      g/l at all the mixing ratios of molasses wastewater and sewage sludge. A hydrogen
      yield of over 50 ml H2/g VS(removed) was obtained from mixed waste of 10% sewage
      sludge and 10 g/l VS (about 10-fold dilution ratio). The optimal chemical oxygen
      demand/ total nitrogen ratio for co-digesting molasses wastewater and sewage
      sludge was between 250 and 300 with a hydrogen yield above 20 ml H2/g
      VS(removed).

PMID- 25394512
TI  - Biochemical characterization of a GDSL-motif esterase from Bacillus sp. K91 with
      a new putative catalytic mechanism.
AB  - The esterase gene Est8 from the thermophilic bacterium Bacillus sp. K91 was
      cloned and expressed in Escherichia coli. The monomeric enzyme exhibited a
      theoretical molecular mass of 24.5 kDa and an optimal activity around 50 degrees
      C at pH 9.0. A model of Est8 was constructed using a hypothetical YxiM precursor
      structure (2O14_A) from Bacillus subtilis as template. The structure showed an
      alpha/beta-hydrolase fold and indicated the presence of a typical catalytic triad
      consisting of Ser-11, Asp-182, and His-185, which were investigated by site
      directed replacements coupled with kinetic characterization. Asp-182 and His-185
      residues were more critical than the Ser-11 residue in the catalytic activity of
      Est8. A comparison of the amino acid sequence showed that Est8 could be grouped
      into the GDSL family and further classified as an SGNH hydrolase. Est8 is a new
      member of the SGNH hydrolase subfamily and may employ a different catalytic
      mechanism. 

PMID- 25394513
TI  - Lactobacillus brevis G101 inhibits the absorption of monosodium glutamate in
      mice.
AB  - To evaluate the effect of Lactobacillus brevis G-101 on absorption of monosodium
      glutamate (MSG), we orally administered MSG with or without G-101 in mice and
      measured the maximum concentration (Cmax) and blood concentration curve (AUC) of
      MSG and gamma- aminobutyric acid (GABA). Oral administration of G-101 (1 * 10(9)
      CFU/mouse) potently inhibited Cmax and AUC of MSG by 97.8% and 94.3%,
      respectively (p < 0.05), but increased those of GABA by 32.1% and 67.7%,
      respectively (p < 0.05). G-101 inhibited the absorption of MSG. These results
      suggest that G-101 may reduce the side effect of MSG by inhibiting the absorption
      of MSG. 

PMID- 25394514
TI  - Calcium ions promote primary renal epithelial cell differentiation into cells
      with bone-associated phenotypes via transforming growth factor-beta1-induced
      epithelial-mesenchymal transition in idiopathic hypercalciuria patients.
AB  - The present study aimed to identify the characteristics and cross-talk between
      transforming growth factor beta1 (TGF-beta1) and calcium ions in nephrolithiasis
      patients with idiopathic hypercalciuria (IH) in order to elucidate the potential
      mechanisms underlying changes in cell phenotype induced by bone-associated
      factors and their influence on renal nephrolithiasis formation. Blood samples
      from a total of 29 nephrolithiasis patients with IH, 29 renal stone patients
      without IH and 29 healthy age-matched normal controls were subjected to
      quantification of peripheral serum TGF-beta1, osteopontin (OPN) and bone
      morphogenetic protein 2 (BMP2) using ELISA. This was followed by detection of
      BMP2, OPN and 1,25-dihydroxyvitamin D3 receptor (VDR) mRNA and protein levels in
      primary renal epithelial cells (PRECs) of IH and HK-2 human proximal tubular cell
      lines (control) using reverse transcription quantitative polymerase chain
      reaction (RT-qPCR) and western blot analyses. The mRNA expression levels of BMP2,
      OPN and VDR in PRECs and HK-2 were evaluated following stimulation with various
      concentrations of TGF-beta1 (0.5, 2.0 and 5.0 ng/ml), Ca2+ (0.5, 1.5 and 2.5 mM)
      or TGF-beta1 and Ca2+ combined using RT-qPCR, respectively. TGF-beta1, BMP2 and
      OPN expression levels in patients with IH were all significantly higher than
      those in the control group. The mRNA and protein expression levels of BMP2 and
      VDR were significantly higher in PRECs than those in HK-2 cells. Following
      incubation with TGF-beta1 and/or Ca2+, the mRNA expression levels of BMP2, OPN
      and VDR in PRECs increased in a dose-dependent manner; however, no significant
      differences were observed in HK-2 cells with increasing TGF-beta1 dosage. Co
      incubation with TGF-beta1 and Ca2+ in PRECs and HK-2 cell lines resulted in
      similar effects and the expression of BMP2, OPN and VDR mRNA increased in a time
      dependent manner. In conclusion, the results of the present study demonstrated
      that TGF-beta1 regulated the expression of BMP2, OPN and VDR in PRECs, but not in
      HK-2 cells. Co-incubation with TGF-beta1 and Ca2+ significantly increased the
      expression levels of bone-associated factors in PRECs and HK-2 cells, which
      suggested that this process may be partially responsible for the pathogenesis of
      calcium stone development, and also associated with bone formation and the TGF
      beta1-induced epithelial to mesenchymal transition.

PMID- 25394516
TI  - Vaccination with OVA-bound nanoparticles encapsulating IL-7 inhibits the growth
      of OVA-expressing E.G7 tumor cells in vivo.
AB  - Immunotherapy has gained special attention due to its specific effects on tumor
      cells and systemic action to block metastasis. We recently demonstrated that
      ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) can
      manipulate humoral immune responses. In the present study, we aimed to ascertain
      whether vaccination with OVA-NPs entrapping IL-7 (OVA-NPs-IL-7) are able to
      induce antitumor immune responses in vivo. Pretreatment with a subcutaneous
      inoculation of OVA-NPs delayed the growth of thymic lymphoma cells expressing a
      model tumor antigen OVA (E.G7-OVA), and OVA-NPs-IL-7 substantially blocked the
      growth of E.G7-OVA tumor cells, although NPs-IL-7 alone had a meager effect, as
      assessed by the mean tumor size and the percentage of tumor-free mice. However,
      pretreatment with OVA-NPs-IL-7 failed to reduce the growth of parental thymic
      tumor cells, suggesting that the antitumor effect was antigen-specific. A
      tetramer assay revealed that vaccination with OVA-NPs-IL-7 tended to enhance the
      proportion of cytotoxic T cells (CTLs) specific for OVA. When the tumor-free mice
      inoculated with OVA-NPs-IL-7 plus EG.7 cells were rechallenged with E.G7-OVA
      cells, they demonstrated reduced growth compared with that in the control mice.
      Thus, a single subcutaneous injection of OVA-NPs-IL-7 into mice induced tumor
      specific and also memory-like immune responses, resulting in regression of tumor
      cells. Antigens on NPs entrapping IL-7 would be a promising carrier to develop
      and enhance immune responses, including humoral and cellular immunity as well as
      a method of drug delivery to a specific target of interest.

PMID- 25394515
TI  - Genomic landscape of metastatic colorectal cancer.
AB  - Response to drug therapy in individual colorectal cancer (CRC) patients is
      associated with tumour biology. Here we describe the genomic landscape of tumour
      samples of a homogeneous well-annotated series of patients with metastatic CRC
      (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number
      aberrations of 349 patients are determined. Within three treatment arms, 194
      chromosomal subregions are associated with progression-free survival (PFS;
      uncorrected single-test P-values <0.005). These subregions are filtered for
      effect on messenger RNA expression, using an independent data set from The Cancer
      Genome Atlas which returned 171 genes. Three chromosomal regions are associated
      with a significant difference in PFS between treatment arms with or without
      irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with
      sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape
      of mCRC reveals a number of DNA copy number aberrations associated with response
      to drug therapy. 

PMID- 25394517
TI  - Phase-controlled synthesis of alpha-NiS nanoparticles confined in carbon nanorods
      for high performance supercapacitors.
AB  - A facile and phase-controlled synthesis of alpha-NiS nanoparticles (NPs) embedded
      in carbon nanorods (CRs) is reported by in-situ sulfurating the preformed Ni/CRs.
      The nanopore confinement by the carbon matrix is essential for the formation of
      alpha-NiS and preventing its transition to beta-phase, which is in strong
      contrast to large aggregated beta-NiS particles grown freely without the
      confinement of CRs. When used as electrochemical electrode, the hybrid
      electrochemical charge storage of the ultrasmall alpha-NiS nanoparticels
      dispersed in CRs is benefit for the high capacitor (1092, 946, 835, 740 F g(-1)
      at current densities of 1, 2, 5, 10 A g(-1), respectively.). While the high
      electrochemical stability (approximately 100% retention of specific capacitance
      after 2000 charge/discharge cycles) is attributed to the supercapacitor-battery
      electrode, which makes synergistic effect of capacitor (CRs) and battery (NiS
      NPs) components rather than a merely additive composite. This work not only
      suggests a general approach for phase-controlled synthesis of nickel sulfide but
      also opens the door to the rational design and fabrication of novel nickel
      based/carbon hybrid supercapacitor-battery electrode materials.

PMID- 25394518
TI  - Understanding Afghan healthcare providers: a qualitative study of the culture of
      care in a Kabul maternity hospital.
AB  - OBJECTIVE: To analyse the culture of a Kabul maternity hospital to understand the
      perspectives of healthcare providers on their roles, experiences, values and
      motivations and the impact of these determinants on the care of perinatal women
      and their babies. DESIGN: Qualitative ethnographic study. SETTING: A maternity
      hospital, Afghanistan. POPULATION: Doctors, midwives and care assistants.
      METHODS: Six weeks of observation followed by 22 semi-structured interviews and
      four informal group discussions with staff, two focus group discussions with
      women and 41 background interviews with Afghan and non-Afghan medical and
      cultural experts. MAIN OUTCOME MEASURES: The culture of care in an Afghan
      maternity hospital. RESULTS: A large workload, high proportion of complicated
      cases and poor staff organisation affected the quality of care. Cultural values,
      social and family pressures influenced the motivation and priorities of
      healthcare providers. Nepotism and cronyism created inequality in clinical
      training and support and undermined the authority of management to improve
      standards of care. Staff without powerful connections were vulnerable in a
      punitive inequitable environment-fearing humiliation, blame and the loss of
      employment. CONCLUSIONS: Suboptimal care put the lives of women and babies at
      risk and was, in part, the result of conflicting priorities. The underlying
      motivation of staff appeared to be the socio-economic survival of their own
      families. The hospital culture closely mirrored the culture and core values of
      Afghan society. In setting priorities for women's health post-2015 Millennium
      Development Goals, understanding the context-specific pressures on staff is key
      to more effective programme interventions and sustainability.

PMID- 25394519
TI  - Evidence of sigma- and pi-dimerization in a series of phenalenyls.
AB  - Phenalenyl and a wide variety of its derivatives form stable radicals, which
      often associate in various aggregates with interesting properties that include
      magnetism and high electrical conductivity. The two main modes of aggregation
      involve pi-stacking pancake multicenter bond formation and sigma-bond formation.
      We explore the energetics of the various sigma- and pi-dimers for six phenalenyl
      derivatives with both computational and experimental methods. A modern density
      functional theory (M05-2X) is used to survey the potential energy surface
      revealing the mechanism of the aggregation. In order to enrich experimental data,
      the triphenyl and trimethyl derivatives are newly prepared and their aggregation
      behaviors are investigated by various analytical methods including ESR, (1)H NMR,
      UV-vis, and single-crystal X-ray diffraction. The agreement between computations
      and experiments are very good forming the basis of describing trends in this
      series. We find that pi-dimer formation can proceed via an asynchronous concerted
      path from the monomers or in a stepwise process via sigma-dimers. The strength of
      the pi-stacking pancake interaction depends strongly on substituents and covers a
      wide range both in terms of binding energies and contact distances. The spin
      densities in the pi-stacking dimers reflect these trends and display a wide range
      of diradicaloid characters. Many sigma-dimer configurations compete some of which
      are separated by small barriers leading to fluxional structures between sigma
      bonded configurations or sigma- and pi-bonded configurations. 

PMID- 25394520
TI  - Childhood ADHD Potentiates the Association Between Problematic Drinking and
      Intimate Partner Violence.
AB  - OBJECTIVE: Excessive alcohol consumption increases risk of perpetrating intimate
      partner violence (IPV). ADHD is associated with problematic drinking and IPV, but
      it is unclear whether problem drinkers with ADHD are more likely than those
      without ADHD to perpetrate IPV. METHOD: We compared the strength of association
      between problem drinking trajectories and IPV perpetration among 19- to 24-year
      old men with ( n = 241) and without ( n = 180) childhood ADHD. RESULTS: Men with
      ADHD who reported higher heavy episodic drinking or alcohol use problems at age
      19, and slower decreases in alcohol use problems from age 19 to 24, were more
      likely to perpetrate IPV than problem drinkers without ADHD, among whom the same
      associations were non-significant. Associations between problem drinking and IPV
      were not attenuated in adults with ADHD upon controlling for antisocial
      personality disorder. CONCLUSION: Study findings highlight the heightened risk of
      problem drinkers with ADHD perpetrating IPV.

PMID- 25394521
TI  - [Dermatologic surgery on the scalp].
AB  - Soft tissue defects of the scalp can be closed with varying techniques depending
      on size and depth of the defect. While small and superficial defects can be
      closed primarily or be left open for secondary intention healing, larger and
      deeper defects may need flaps or skin grafts. Extensive defects may require
      combined flaps or vacuum assisted closure techniques. Defects of the periosteum
      with denuded skull bone must be treated immediately to avoid bony complications.
      Usually, the tabula externa is fenestrated with holes or abraded totally to
      create better healing conditions. Granulation tissue may be induced on the
      properly prepared skull with vacuum-assisted closure, by using collagen sheets or
      with dermal skin substitutes. New developments in tissue engineering will surely
      provide new techniques for dealing with deep and extensive soft tissue defects.

PMID- 25394522
TI  - [Psoriasis and eczema on the scalp].
AB  - BACKGROUND: Diseases of the scalp are a severe burden for affected patients
      because they are often visible, frequently pruritic and hard to treat. Therefore,
      a proper diagnosis is extremely important. DIAGNOSIS: If the patient presents
      with erythematous, scaly skin lesions of the scalp, psoriasis has to be
      differentiated from atopic eczema, seborrheic eczema and contact eczema (allergic
      or toxic). The inspection of the entire body as well as a detailed history are
      essential for establishing the diagnosis. THERAPY: Topical corticosteroids are
      the therapeutic agents of choice for all of these scalp diseases. In individual
      cases immunosuppressive systemic treatments may be required. Azole antimycotics
      are not only used for seborrheic dermatitis but may also be indicated for
      treatment of atopic dermatitis or psoriasis of the scalp. OBJECTIVES: This review
      provides an overview of the clinical differences between scalp psoriasis and the
      various forms of eczema and of their therapeutic options. It also highlights the
      differential diagnosis between toxic and allergic contact eczema of the scalp.

PMID- 25394523
TI  - [Pigment accumulation in a sentinel lymph node patient with malignant melanoma.
      Lymph node tattoo].

PMID- 25394524
TI  - [Frequent pathogen-induced diseases of the scalp].
AB  - BACKGROUND: The scalp represents a special region for the manifestation of
      pathogen-induced diseases. OBJECTIVE: This article describes practice-relevant
      pathogen-induced skin diseases caused by bacteria, fungi, viruses and parasites.
      MATERIAL AND METHODS: Currently available publications were evaluated with
      special reference to therapeutic developments. RESULTS: Bacterial infections of
      the scalp must be treated consistently in the initial stages in order to avoid
      severe consequences. Skin diseases caused by fungi must be treated topically
      (e.g. neonatal cephalic pustulosis) or systemically and topically (e.g. tinea).
      Varicella zoster diseases in children and adults are treated differently. A safe
      and highly effective physically effective substance is now available for
      pediculosis capitis (head lice). CONCLUSION: Dermatologically relevant pathogen
      induced diseases of the scalp can be well treated; however, tinea capitis still
      proves to be a special problem due to a lack of approved substances and long-term
      therapy.

PMID- 25394525
TI  - Medication-administration errors in an urban mental health hospital: a direct
      observation study.
AB  - In the present study, we aimed to identify the incidence, type, and potential
      clinical consequence of medication-administration errors made in a mental health
      hospital, and to investigate factors that might increase the risk of error. A
      prospective, direct observational technique was used to collect data from nurse
      medication rounds on each of the hospital's 43 inpatient wards. Regression
      analysis was used to identify potential error predictors. During the 172
      medication rounds observed, 139 errors were detected in 4177 (3.3%)
      opportunities. The most common error was incorrect dose omission (52/139, 37%).
      Other common errors included incorrect dose (25/139, 18%), incorrect form
      (16/139, 12%), and incorrect time (12/139, 9%). Fifteen (11%) of the errors were
      of serious clinical severity; the rest were of negligible or minor severity.
      Factors that increased the risk of error included the nurse interrupting the
      medication round to attend to another activity, an increased number of 'when
      required' doses of medication administered, a higher number of patients on the
      ward, and an increased number of doses of medication due. These findings suggest
      that providers of inpatient mental health-care services should adopt medicine
      administration systems that minimize task interruption and the use of 'when
      required' medication, as well as taking steps to reduce nursing workload. 

PMID- 25394526
TI  - Pubic hair preferences, reasons for removal, and associated genital symptoms:
      comparisons between men and women.
AB  - INTRODUCTION: Pubic hair grooming and removal are common behaviors among men and
      women. However, little is known about the reasons for grooming, preferred pubic
      hairstyle of sexual partners, and symptoms associated with regular grooming.
      AIMS: This study aims to assess pubic hair removal/grooming practices, pubic
      hairstyle preferences, and genital outcomes associated with pubic hair removal
      among men and women in a college sample. METHODS: Data were gathered from 1,110
      participants (671 women and 439 men) at a large public Midwestern university and
      a small Southern public university. MAIN OUTCOME MEASURES: Items assessed
      demographics, pubic hair grooming and removal practices in the past 4 weeks,
      reasons for pubic hair status, preference for pubic hairstyle of sexual partners,
      and symptoms associated with removal and grooming. RESULTS: Most (95%)
      participants had removed their pubic hair on at least one occasion in the past 4
      weeks with shaving being the most commonly reported hair removal technique by
      women (82%) and men (49%). Women were significantly more likely to report their
      typical status as hair-free (50% vs. 19%; chi(2) = 165.528, P < 0.001) and men
      were significantly more likely to prefer a hair-free sexual partner (60% vs. 24%;
      chi(2) = 211.712, P < 0.001). Genital itching was experienced on at least one
      occasion by 80.3% of pubic hair groomers and was the most commonly reported side
      effect. CONCLUSION: Genital grooming and pubic hair removal are common practices
      among both men and women of college-age. Women are likely to report stronger
      associations with feelings of cleanliness, comfort, sex appeal, social norms of
      their peer group, and affordability as reasons for their chosen pubic hair style.
      Women also report more experiences with genital side effects of pubic hair
      removal, an expected result as women are removing pubic hair more frequently and
      more completely than their male counterparts.

PMID- 25394527
TI  - Early markers of cardiovascular risk in chronic kidney disease.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) present a markedly
      increased cardiovascular (CV) morbidity and mortality since the early stages and
      have a high prevalence of accelerated atherosclerosis, inflammation and
      endothelial dysfunction. Nontraditional cardiovascular risk factors and serum
      cardiac biomarkers would contribute to explain this increased morbidity. AIM: The
      aim is to investigate the relation among serum cardiac biomarkers (N-terminal pro
      brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), nontraditional
      cardiovascular risk factors (serum uric acid, homocysteine), inflammatory indexes
      (C-reactive protein (CRP) serum ferritin, fibrinogen) and noninvasive predictors
      of atherosclerosis (carotid intima-media thickness (cIMT), brachial artery flow
      mediated dilation (baFMD), and left ventricular mass index (LVMI)) in CKD
      patients. MATERIALS AND METHODS: In 50 patients with CKD in stage 2/3 kidney
      disease outcomes quality initiative (KDOQI) and 18 age- and sex-matched healthy
      controls, the following parameters were measured: cardiac markers (cTnT and NT
      proBNP), renal function, inflammatory markers (CRP, serum ferritin and
      fibrinogen), serum uric acid and homocysteine. We have also evaluated LVMIs, cIMT
      and baFMD. RESULTS: In our study, we showed an increase of NT-proBNP and the
      serum cTnT, of serum uric acid and homocysteine with a positive correlation with
      the increase of cIMT and LVMI and reduced baFMD compared with the controls.
      CONCLUSIONS: Serum cardiac biomarkers and nontraditional cardiovascular risk
      factors increase already in the stage 2/3 KDOQI contributing to explain the high
      cardiovascular morbidity and mortality of these patients. The NT-proBNP seems to
      have a rise earlier compared with serum cTnT; however, both seemed to be a useful
      clinical biomarker for evaluating noninvasive predictors of atherosclerosis in
      CKD patients.

PMID- 25394528
TI  - Inflammatory markers as mortality predictors in continuous ambulatory peritoneal
      dialysis patients.
AB  - BACKGROUND/AIM: Besides peritonitis, the most common complication, indicators of
      chronic inflammation are also present in patients treated by peritoneal dialysis.
      The aim of this study was to analyze the predictive value of inflammatory
      parameters on mortality of continuous ambulatory peritoneal dialysis (CAPD)
      patients. METHODS: Eighty-seven patients (57 males), aged from 30 to 85 [62.92
      (10.61)] years who had been treated by a chronic program of CAPD for 3-113 months
      were analyzed. The basal period lasted 3 months with a follow-up of 30 months.
      Clinical parameters, dialysis adequacy and laboratory parameters including some
      inflammatory markers: serum amyloid-A (SAA), high sensitive C-reactive protein
      (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR) and leukocytes were
      determined for each patient. Cox regression analysis selected the parameters of
      univariate and multivariate survival analysis. RESULTS: During the follow-up
      period, 37 patients (42.5%) died. Univariate analysis selected the following
      potential mortality predictors (p<0.10): age, months on CAPD, residual urine
      output, presence of cerebrovascular insult (CVI), KT/V, serum urea and albumin
      concentrations, SAA, hs-CRP, fibrinogen and ESR. In the multivariate survival
      analysis four models were created, each with a single inflammatory parameter. In
      all of these models, besides the age and CVI, inflammatory parameters were the
      most significant mortality predictors. When the inflammatory markers were
      analyzed altogether, multivariate analysis established that independent mortality
      predictors in this group of patients were: SAA, age and CVI. CONCLUSION: It may
      be concluded that in this studied group treated by CAPD, SAA was the most
      significant independent mortality predictor among the analyzed inflammatory
      markers.

PMID- 25394529
TI  - Can neutrophil-lymphocyte ratio be independent risk factor for predicting acute
      kidney injury in patients with severe sepsis?
AB  - AIM: Neutrophil-lymphocyte ratio (NLR) is an easily calculated, sensitive, and
      accurate marker for prognosis and diagnosing sepsis, cardiovascular disease and
      cancer. As sepsis and septic shock are main causes of acute kidney injury (AKI)
      intensive care unit (ICU), we investigated whether NLR is an early predictor of
      AKI in patients with severe sepsis. We compared NLR's predictive power with that
      of other inflammation-related variables. METHODS: Between December 2011 and
      November 2013, we enrolled 118 consecutive cases with severe sepsis admitted to
      ICU in this retrospective study. Levels of C-reactive protein (CRP), NLR, and
      white blood cell count (WBC) were recorded on admission and patients' renal
      function was monitored for seven consecutive days. RESULTS: The rate of AKI
      occurrence 7 days after enrollment was 57.6%. NLR levels were higher in the AKI
      group (Group 1) than in the non-AKI group (Group 2) on the day of ICU admission
      (p<0.001). AKI development was independently associated with NLR, Acute
      Physiology and Chronic Health Evaluation II (APACHE II) and duration of invasive
      mechanical ventilation (MV) in multivariate logistic regression analysis. The
      area under the receiver-operating characteristic (ROC) curve of NLR for
      predicting AKI was 0.986, which was superior to WBC and CRP (p<0.05). The cut-off
      value of 10.15 for NLR had the highest validity for predicting AKI in patients
      with severe sepsis. The sensitivity, specificity, negative-predictive value
      (NPV), and positive-predictive value (PPV), for this cut-off value was 90.2%,
      92.9%, 90.4%, and 92.7%, respectively. CONCLUSION: NLR is superior to CRP, and
      WBC for predicting the development of AKI in patients with severe sepsis.

PMID- 25394530
TI  - Bcii--RFLP profiles for serum amiloid A1 and mutated MEFV gene prevalence in
      chronic renal failure patients requiring long-term hemodialysis.
AB  - BACKGROUND AND AIM: There is an increased mortality risk in long-term
      hemodialysis patients of renal failure due to the chronic inflammation. The
      relationship between the chronic renal failure (CRF) and the role of familial
      genetic markers remains incompletely understood. In the current study, it was
      aimed to find out the prevalence of common MEFV gene mutations and BcII
      polymorphism in serum amyloid A1 (SAA1) gene in chronic renal patients (CRF) who
      require long-term hemodialysis. METHOD: Current cohort includes 242 CRF patients
      and 245 healthy individuals from the same population. Total genomic DNA was
      isolated from peripheral blood-EDTA samples and genotyping of target MEFV gene
      was carried out by reverse hybridization Strip Assay and real-time techniques.
      The SAA1 gene was genotyped by the BclI-RFLP method. RESULTS: Increased mutated
      MEFV genotypes were found in current CRF patients when compared with the control
      group from the same ethnicity and the difference was statistically significant
      (Table 2) (OR: 4.9401, 95% CI: 3.0694-7.9509), p<0.0001. The most frequent point
      mutations were M694V and E148Q. The mutated T allel frequency in the SAA1 gene
      was also different when compared with the healthy controls and the difference was
      found to be statistically significant (chi2: 13.18; p=0.000). CONCLUSIONS: The
      current results indicate the germ-line mutations in both genetic biomarkers (MEFV
      and SAA1 genes) that are related to inflammation and amyloidosis processes may
      play a crucial role in CRF pathogenesis due to the long-term chronic
      inflammation.

PMID- 25394531
TI  - Tear function in patients with chronic renal failure undergoing hemodialysis.
AB  - OBJECTIVES: To evaluate dry eye symptoms and clinical tear film alterations in
      patients with chronic renal failure (CRF). MATERIALS AND METHODS: Thirty-five non
      diabetic CRF patients undergoing hemodialysis, and 31 healthy individuals were
      enrolled. An ocular surface disease index questionnaire (OSDI) was administered,
      and after a complete ocular examination, Schirmer and tear break-up time (TBUT)
      tests were performed. RESULTS: OSDI scores were significantly higher (p<0.01) and
      TBUT tests were significantly lower (p=0.01) in CRF patients than in the control
      group. Schirmer test results were also lower in the CRF patients group, but
      lacked statistical significance (p=0.20). CONCLUSION: Patients with CRF should be
      advised to obtain an ophthalmic examination, especially for dry eye.

PMID- 25394533
TI  - Grass-green urine from propofol infusion.
AB  - Green urine from propofol infusion is a benign and rare side effect. The
      discolouration appears when clearance of propofol exceeds hepatic elimination,
      and extrahepatic elimination of propofol occurs. This case report presents a 24
      year-old male with grass green discolouration of urine based on propofol
      infusion. 

PMID- 25394532
TI  - Role of MTA2 in human cancer.
AB  - Metastasis is the ultimate cause of death for most cancer patients. While many
      mechanisms have been delineated for regulation of growth and tumor initiation of
      the primary tumor, very little is known about the process of metastasis.
      Metastasis requires dynamic alteration of cellular processes in order for cells
      to disseminate from the primary tumor to distant sites. These alterations often
      involve dramatic changes in the regulation of cytoskeletal and cell-environment
      interactions. Furthermore, controlled refinement of these interactions requires
      feedback to regulatory networks in the nucleus. MTA2 is a member of the
      metastasis tumor-associated family of transcriptional regulators and is a central
      component of the nucleosome remodeling and histone deacetylation complex. MTA2
      acts as a central hub for cytoskeletal organization and transcription and
      provides a link between nuclear and cytoskeletal organization. We will focus on
      MTA2 in this chapter, especially its role in breast cancer metastasis. 

PMID- 25394534
TI  - Enteric fever imported to the Czech Republic: epidemiology, clinical
      characteristics and antimicrobial susceptibility.
AB  - The aim of this study was to describe epidemiological and clinical
      characteristics of imported enteric fever in Czech travellers and to determine
      the antimicrobial susceptibility of isolated strains. Retrospective descriptive
      study included adult patients treated with enteric fever at Hospital Na Bulovce
      during January 2004-December 2012. A case of typhoid or paratyphoid fever was
      defined as isolation of Salmonella Typhi or Paratyphi from blood or stool. During
      the study period, there have been diagnosed 19 cases of enteric fever (12 males
      and 7 females) with age median of 30 years; 14 cases were caused by Salmonella
      Typhi and 5 cases by S. Paratyphi A. The infection has been acquired in South
      Asia (16 patients; 84.2 %), in Africa (Egypt, Angola) in two cases (10.5 %), and
      in Mexico (1; 5.3 %). Symptoms included fever (all patients), diarrhoea (16
      cases; 84.2 %), headache (9; 47.4 %), and abdominal pain (7; 36.8 %). Seventeen
      patients (89.5 %) were treated with fluoroquinolones; however, the treatment
      failure was observed in seven of them (41.2 %). Decreased ciprofloxacin
      susceptibility was detected in eight strains (66.7 %), and one strain (8.3 %) was
      multidrug resistant. Sequence analysis of quinolone resistance-determining
      regions (QRDR) of the gyrA gene revealed the presence of amino acid substitutions
      in all tested isolates with decreased ciprofloxacin susceptibility. Typhoid and
      paratyphoid fevers represent epidemiologically important diseases that may lead
      to potentially life-threatening complications. Major issue in the management of
      enteric fever represents the non-susceptibility of Salmonella strains to
      fluoroquinolones and other antimicrobials.

PMID- 25394535
TI  - Extraction of brewer's yeasts using different methods of cell disruption for
      practical biodiesel production.
AB  - The methods of preparation of fatty acids from brewer's yeast and its use in
      production of biofuels and in different branches of industry are described.
      Isolation of fatty acids from cell lipids includes cell disintegration (e.g.,
      with liquid nitrogen, KOH, NaOH, petroleum ether, nitrogenous basic compounds,
      etc.) and subsequent processing of extracted lipids, including analysis of fatty
      acid and computing of biodiesel properties such as viscosity, density, cloud
      point, and cetane number. Methyl esters obtained from brewer's waste yeast are
      well suited for the production of biodiesel. All 49 samples (7 breweries and 7
      methods) meet the requirements for biodiesel quality in both the composition of
      fatty acids and the properties of the biofuel required by the US and EU
      standards. 

PMID- 25394536
TI  - Nudging physician prescription decisions by partitioning the order set: results
      of a vignette-based study.
AB  - BACKGROUND: Healthcare professionals are rapidly adopting electronic health
      records (EHRs). Within EHRs, seemingly innocuous menu design configurations can
      influence provider decisions for better or worse. OBJECTIVE: The purpose of this
      study was to examine whether the grouping of menu items systematically affects
      prescribing practices among primary care providers. PARTICIPANTS: We surveyed 166
      primary care providers in a research network of practices in the greater Chicago
      area, of whom 84 responded (51% response rate). Respondents and non-respondents
      were similar on all observable dimensions except that respondents were more
      likely to work in an academic setting. DESIGN: The questionnaire consisted of
      seven clinical vignettes. Each vignette described typical signs and symptoms for
      acute respiratory infections, and providers chose treatments from a menu of
      options. For each vignette, providers were randomly assigned to one of two menu
      partitions. For antibiotic-inappropriate vignettes, the treatment menu either
      listed over-the-counter (OTC) medications individually while grouping
      prescriptions together, or displayed the reverse partition. For antibiotic
      appropriate vignettes, the treatment menu either listed narrow-spectrum
      antibiotics individually while grouping broad-spectrum antibiotics, or displayed
      the reverse partition. MAIN MEASURES: The main outcome was provider treatment
      choice. For antibiotic-inappropriate vignettes, we categorized responses as
      prescription drugs or OTC-only options. For antibiotic-appropriate vignettes, we
      categorized responses as broad- or narrow-spectrum antibiotics. KEY RESULTS:
      Across vignettes, there was an 11.5 percentage point reduction in choosing
      aggressive treatment options (e.g., broad-spectrum antibiotics) when aggressive
      options were grouped compared to when those same options were listed individually
      (95% CI: 2.9 to 20.1%; p = .008). CONCLUSIONS: Provider treatment choice appears
      to be influenced by the grouping of menu options, suggesting that the layout of
      EHR order sets is not an arbitrary exercise. The careful crafting of EHR order
      sets can serve as an important opportunity to improve patient care without
      constraining physicians' ability to prescribe what they believe is best for their
      patients.

PMID- 25394537
TI  - Azithromycin and the treatment of lymphocytic airway inflammation after lung
      transplantation.
AB  - Lymphocytic airway inflammation is a major risk factor for chronic lung allograft
      dysfunction, for which there is no established treatment. We investigated whether
      azithromycin could control lymphocytic airway inflammation and improve allograft
      function. Fifteen lung transplant recipients demonstrating acute allograft
      dysfunction due to isolated lymphocytic airway inflammation were prospectively
      treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC,
      FEV1 , FEF25-75 , Tiffeneau index) and FeNO were assessed before and up to 12
      months after initiation of azithromycin. Radiologic features, local inflammation
      assessed on airway biopsy (rejection score, IL-17(+)  cells/mm(2) lamina propria)
      and broncho-alveolar lavage fluid (total and differential cell counts, chemokine
      and cytokine levels); as well as systemic C-reactive protein levels were compared
      between baseline and after 3 months of treatment. Airflow improved and FeNO
      decreased to baseline levels after 1 month of azithromycin and were sustained
      thereafter. After 3 months of treatment, radiologic abnormalities, submucosal
      cellular inflammation, lavage protein levels of IL-1beta, IL-8/CXCL-8, IP-10/CXCL
      10, RANTES/CCL5, MIP1-alpha/CCL3, MIP-1beta/CCL4, Eotaxin, PDGF-BB, total cell
      count, neutrophils and eosinophils, as well as plasma C-reactive protein levels
      all significantly decreased compared to baseline (p < 0.05). Administration of
      azithromycin was associated with suppression of posttransplant lymphocytic airway
      inflammation and clinical improvement in lung allograft function. 

PMID- 25394538
TI  - Molecular progress on the mapping and cloning of functional genes for blast
      disease in rice (Oryza sativa L.): current status and future considerations.
AB  - Rice blast disease, which is caused by the fungal pathogen Magnaporthe oryzae, is
      a recurring problem in all rice-growing regions of the world. The use of
      resistance (R) genes in rice improvement breeding programmes has been considered
      to be one of the best options for crop protection and blast management.
      Alternatively, quantitative resistance conferred by quantitative trait loci
      (QTLs) is also a valuable resource for the improvement of rice disease
      resistance. In the past, intensive efforts have been made to identify major R
      genes as well as QTLs for blast disease using molecular techniques. A review of
      bibliographic references shows over 100 blast resistance genes and a larger
      number of QTLs (~500) that were mapped to the rice genome. Of the blast
      resistance genes, identified in different genotypes of rice, ~22 have been cloned
      and characterized at the molecular level. In this review, we have summarized the
      reported rice blast resistance genes and QTLs for utilization in future molecular
      breeding programmes to introgress high-degree resistance or to pyramid R-genes in
      commercial cultivars that are susceptible to M. oryzae. The goal of this review
      is to provide an overview of the significant studies in order to update our
      understanding of the molecular progress on rice and M. oryzae. This information
      will assist rice breeders to improve the resistance to rice blast using marker
      assisted selection which continues to be a priority for rice-breeding programmes.

PMID- 25394539
TI  - Phage antibody display libraries: a powerful antibody discovery platform for
      immunotherapy.
AB  - Phage display technology (PDT), a combinatorial screening approach, provides a
      molecular diversity tool for creating libraries of peptides/proteins and
      discovery of new recombinant therapeutics. Expression of proteins such as
      monoclonal antibodies (mAbs) on the surface of filamentous phage can permit the
      selection of high affinity and specificity therapeutic mAbs against virtually any
      target antigen. Using a number of diverse selection platforms (e.g. solid phase,
      solution phase, whole cell and in vivo biopannings), phage antibody libraries
      (PALs) from the start point provides great potential for the isolation of
      functional mAb fragments with diagnostic and/or therapeutic purposes. Given the
      pivotal role of PDT in the discovery of novel therapeutic/diagnostic mAbs, in the
      current review, we provide an overview on PALs and discuss their impact in the
      advancement of engineered mAbs. 

PMID- 25394540
TI  - Hooked on alpha-d-galactosidases: from biomedicine to enzymatic synthesis.
AB  - alpha-d-Galactosidases (EC 3.2.1.22) are enzymes employed in a number of useful
      bio-based applications. We have depicted a comprehensive general survey of alpha
      d-galactosidases from different origin with special emphasis on marine
      example(s). The structures of natural alpha-galactosyl containing compounds are
      described. In addition to 3D structures and mechanisms of action of alpha-d
      galactosidases, different sources, natural function and genetic regulation are
      also covered. Finally, hydrolytic and synthetic exploitations as free or
      immobilized biocatalysts are reviewed. Interest in the synthetic aspects during
      the next years is anticipated for access to important small molecules by green
      technology with an emphasis on alternative selectivity of this class of enzymes
      from different sources. 

PMID- 25394541
TI  - Soft tissue injury of the shoulder after single non-dislocating trauma:
      prevalence and spectrum of intraoperative findings during shoulder arthroscopy
      and treatment results.
AB  - BACKGROUND AND PURPOSE: The purpose of our study was to present the spectrum and
      prevalence of intraarticular lesions in patients with shoulder pain after a
      single non-dislocating shoulder trauma and to evaluate the clinical results
      according to pathology and workers' compensation status. METHODS: Sixty
      consecutive patients (61 shoulders) with shoulder pain following a single non
      dislocating shoulder trauma had shoulder arthroscopy. The indication for surgery
      was either persistent pain for 3 months or longer after trauma and/or an
      intraarticular lesion on MRI. Patients with history of shoulder complaints,
      previous shoulder surgery, a complete rotator cuff tear or a fracture of the
      shoulder girdle were excluded. Intraarticular findings during shoulder
      arthroscopy were retrospectively analyzed. After a minimum follow-up of 1 year
      patients were contacted by telephone interview and ASES score, Simple Shoulder
      Test, Subjective Shoulder Value and residual pain were assessed for the entire
      population and for patients with and without workers' compensation. RESULTS: The
      most common intraarticular findings were SLAP (44.3 %) and Pulley (19.7 %)
      lesions followed by lesions of the anterior or posterior labrum (14.8 %). The
      mean age of the 13 women and 47 men was 41.9 years (SD 10.9). Patients with
      workers' compensation had significantly lower scores than patients without and
      had a significantly lower return to work rate than patients without.
      INTERPRETATION: In patients with persistent shoulder pain after sprain or
      contusion arthroscopy revealed a broad spectrum of intraarticular findings.
      Patients with workers' compensation claims had worse results than those without.
      LEVEL OF EVIDENCE: Case series (Level IV).

PMID- 25394542
TI  - Susceptibility of Sporothrix brasiliensis isolates to amphotericin B, azoles, and
      terbinafine.
AB  - The in vitro activity of the antifungal agents amphotericin B (AMB), itraconazole
      (ITC), posaconazole (PSC), voriconazole (VRC), and terbinafine (TRB) against 32
      Brazilian isolates of Sporothrix brasiliensis, including 16 isolates from a
      recent (2011-2012) epidemic in Rio de Janeiro state, was examined. We describe
      and genotype new isolates and clustered them with 16 older (from 2004 or earlier)
      S. brasiliensis isolates by phylogenetic analysis. We tested both the yeast and
      the mycelium form of all isolates using broth microdilution methods based on the
      reference protocols M38-A2 and M27-A3 (recommended by the Clinical and Laboratory
      Standards Institute). Considering minimum inhibitory concentrations (MICs) and
      minimum fungicidal concentrations (MFCs), TRB was found to be the most active
      drug in vitro for both fungal forms, followed by PSC. Several isolates showed
      high MICs for AMB and/or ITC, which are currently used as first-line therapy for
      sporotrichosis. VRC displayed very low activity against S. brasiliensis isolates.
      The primary morphological modification observed on treated yeasts by transmission
      electron microscopy analysis was changes in cell wall. Our results indicate that
      TRB is the antifungal with the best in vitro activity against S. brasiliensis and
      support the use of TRB as a promising option for the treatment of cutaneous
      and/or lymphocutaneous sporotrichosis. 

PMID- 25394543
TI  - The importance of EN ISO 15189 accreditation of allergen-specific IgE
      determination for reliable in vitro allergy diagnosis.
AB  - BACKGROUND: Allergen-specific serum immunoglobulin E detection and quantification
      have become an important step in allergy diagnosis and follow-up. In line with
      the current trend of laboratory test accreditation to international standards, we
      set out to design and assess an accreditation procedure for allergen-specific
      serum IgE. METHODS: Method validation according to the accreditation procedure
      under the EN ISO 15189 standard was carried out for allergen-specific
      immunoglobulin E determination using the fluoroimmunoenzymatic method
      ImmunoCAP((r)) (ThermoFisher). Data were produced by 25 hospital laboratories in
      France. A total of 29 allergen specificities including mixes, extracts, and
      molecular allergens were assayed. Allergen-specific serum immunoglobulin E
      concentrations ranged from 0.1 to 100 kUA /l. RESULTS: Repeatability,
      reproducibility, and accuracy results fulfilled method validation criteria for
      automated laboratory tests and proved similar irrespective of the allergen
      specificity, allergen-specific serum immunoglobulin E concentration, or
      individual laboratory. CONCLUSION: Allergen-specific serum immunoglobulin E
      determination with the fluoroimmunoenzymatic method ImmunoCAP((r)) is a highly
      repeatable, reproducible, and accurate method which may be considered as a single
      analyte assay in view of the EN ISO 15189 accreditation procedure.

PMID- 25394544
TI  - Structural and developmental variability in the female gametophyte of
      Griffithella hookeriana, Polypleurum stylosum, and Zeylanidium lichenoides and
      its bearing on the occurrence of single fertilization in Podostemaceae.
AB  - Angiosperms are characterized by the phenomenon of double fertilization with
      Podostemaceae as an exception that appears to extend to the entire family. Our
      earlier work demonstrated the cause of failure of double fertilization and
      ascertained the occurrence of single fertilization in Dalzellia zeylanica
      (Tristichoideae, Podostemaceae). In continuation with this work, three more
      members, i.e., Griffithella hookeriana (Tul.) Warming, Polypleurum stylosum
      (Wight) Hall, and Zeylanidium lichenoides (Kurz) Engl. (Podostemoideae), have
      been investigated in the present work. We studied the ontogenetic development of
      female gametophyte and tracked the path of the two sperm cells from the time of
      their formation in the pollen tube through their entry into the synergid and
      gamete fusion. We report the occurrence of a remarkably reduced 3-nucleate, 3
      celled mature female gametophyte consisting of an egg cell and two synergids in
      all the three genera. Interestingly, the central cell is formed during female
      gametophyte development, but exhibits a species-specific, limited life span, and
      eventually degenerates prior to the entry of the pollen tube into the synergid,
      resulting in a failure of double fertilization. Sperm dimorphism on the basis of
      fluorochrome stainability has been recorded in Z. lichenoides. Further,
      morphogenetic constraints on the part of male (sperm selection, functional
      reductionism) and female gametophyte (structural reductionism, inaccessibility of
      central cell) presumably ensure the failure of double fertilization in these
      species. Thus, loss of double fertilization in this family is likely a derived
      condition.

PMID- 25394545
TI  - Gleaning after the European Headache Federation consensus statement on refractory
      chronic migraine.

PMID- 25394546
TI  - Better-than-average and worse-than-average hospitals may not significantly differ
      from average hospitals: an analysis of Medicare Hospital Compare ratings.
AB  - BACKGROUND: Public report card designers aim to provide comprehensible provider
      performance information to consumers. Report cards often display classifications
      of providers into performance tiers that reflect whether performance is
      statistically significantly above or below average or not statistically
      significantly different from average. To further enhance the salience of public
      reporting to consumers, report card websites often allow a user to compare a
      subset of selected providers on tiered performance rather than direct statistical
      comparisons of the providers in a consumer's personal choice set. OBJECTIVE: We
      illustrate the differences in conclusions drawn about relative provider
      performance using tiers versus conducing statistical tests to assess performance
      differences. METHODS: Using publicly available cross-sectional data from Medicare
      Hospital Compare on three mortality and three readmission outcome measures, we
      compared each provider in the top or bottom performance tier with those in the
      middle tier and assessed the proportion of such comparisons that exhibited no
      statistically significant differences. RESULTS: Across the six outcomes, 1.3-6.1%
      of hospitals were classified in the top tier. Each top-tier hospital did not
      statistically significantly differ in performance from at least one mid-tier
      hospital. The percentages of mid-tier hospitals that were not statistically
      significantly different from a given top-tier hospital were 74.3-81.1%. The
      percentages of hospitals classified as bottom tier were 0.6-4.0%. Each bottom
      tier hospital showed no statistically significant difference from at least one
      mid-tier hospital. The percentage of mid-tier hospitals that were not
      significantly different from a bottom-tier hospital ranged from 60.4% to 74.8%.
      CONCLUSIONS: Our analyses illustrate the need for further innovations in the
      design of public report cards to enhance their salience for consumers.

PMID- 25394547
TI  - Particulate versus non-particulate steroids for lumbar transforaminal or
      interlaminar epidural steroid injections: an update.

PMID- 25394548
TI  - Heme-binding-mediated negative regulation of the tryptophan metabolic enzyme
      indoleamine 2,3-dioxygenase 1 (IDO1) by IDO2.
AB  - Indoleamine 2,3-dioxygenases (IDOs) are tryptophan-catabolizing enzymes with
      immunomodulatory functions. However, the biological role of IDO2 and its
      relationship with IDO1 are unknown. To assess the relationship between IDO2 and
      IDO1, we investigated the effects of co-expression of human (h) IDO2 on hIDO1
      activity. Cells co-expressing hIDO1 and hIDO2 showed reduced tryptophan metabolic
      activity compared with those expressing hIDO1 only. In a proteomic analysis,
      hIDO1-expressing cells exhibited enhanced expression of proteins related to the
      cell cycle and amino acid metabolism, and decreased expression of proteins
      related to cell survival. However, cells co-expressing hIDO1 and hIDO2 showed
      enhanced expression of negative regulators of cell apoptosis compared with those
      expressing hIDO1 only. Co-expression of hIDO1 and hIDO2 rescued the cell death
      induced by tryptophan-depletion through hIDO1 activity. Cells expressing only
      hIDO2 exhibited no marked differences in proteome profiles or cell growth
      compared with mock-transfectants. Cellular tryptophan metabolic activity and cell
      death were restored by co-expressing the hIDO2 mutant substituting the histidine
      360 residue for alanine. These results demonstrate that hIDO2 plays a novel role
      as a negative regulator of hIDO1 by competing for heme-binding with hIDO1, and
      provide information useful for development of therapeutic strategies to control
      cancer and immunological disorders that target IDO molecules. 

PMID- 25394549
TI  - Effect of abdomen massage for prevention of feeding intolerance in preterm
      infants.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of abdominal
      massage on feeding tolerance in stable preterm infants fed minimal enteral
      nutrition. METHODS: The study was conducted on a control-grouped pre-test, post
      test quasi-experimental design at the neonatal intensive care unit of a
      university hospital in Turkey between March and July 2012. Abdominal massage was
      applied to the massage group subjects for 15 minutes, 2 times daily, before the
      subject was fed starting in the 5-day study period. RESULTS: The study was
      conducted with 27 subjects, 14 in the massage group and 13 in the control group.
      When frequency of defecation measurements were analysed, the difference between
      the first day and last day of the study was not statistically significant in the
      massage group. However, when daily weight gain, frequency of vomiting, abdominal
      circumference and gastric residual volume excess measurements were analysed, the
      differences between the first day and last day of the study were statistically
      significant in the massage group. CONCLUSIONS: In accordance with the results of
      the study, we suggest that nurses should apply abdominal massage twice a day as
      an intervention helping to prevent gastric residual volume excess and abdominal
      distension in enterally fed preterm infants.

PMID- 25394550
TI  - Usability of online psychoeducation for siblings of people with psychosis.
AB  - OBJECTIVES: The E Sibling Project aims to address the needs of siblings of
      individuals affected by psychosis through provision of a comprehensive online
      intervention. The online intervention comprises four core elements, including:
      information on psychosis; various coping and promoting well-being strategies;
      siblings' blogs and discussion forum with peers; and an "Ask the Experts"
      function. After the intervention-prototype was developed, we tested its
      feasibility, usability and acceptability by siblings. METHODS: We evaluated the
      usability of the intervention-prototype using a non-randomised usability study
      with siblings of individuals diagnosed with psychosis. The usability study
      adapted Poulson et al's framework to collect subjective feedback from
      participants on ease of use, perceived usefulness and acceptability, together
      with objective usage data on the intervention. RESULTS: Twenty siblings were
      recruited to the usability test; 19 tried out the resource-prototype over a 4
      week period and 17 completed the online evaluation after using the intervention.
      In total, 906 page-views were made by the participants and each spent about two
      hours using the resource. Participants evaluated the intervention as helpful,
      relevant and useful in terms of content, design and usability. Developments are
      needed to improve the navigation and intuitiveness of the resource. CONCLUSIONS:
      Using an internet-based information-giving and peer support intervention to
      promote wellbeing and coping is feasible and acceptable to siblings of people
      with psychosis.

PMID- 25394551
TI  - Delineating margins of lentigo maligna using a hyperspectral imaging system.
AB  - Lentigo maligna (LM) is an in situ form of melanoma which can progress into
      invasive lentigo maligna melanoma (LMM). Variations in the pigmentation and thus
      visibility of the tumour make assessment of lesion borders challenging. We tested
      hyperspectral imaging system (HIS) in in vivo preoperative delineation of LM and
      LMM margins. We compared lesion margins delineated by HIS with those estimated
      clinically, and confirmed histologically. A total of 14 LMs and 5 LMMs in 19
      patients were included. HIS analysis matched the histo-pathological analysis in
      18/19 (94.7%) cases while in 1/19 (5.3%) cases HIS showed lesion extension not
      confirmed by histopathology (false positives). Compared to clinical examination,
      HIS defined lesion borders more accurately in 10/19 (52.6%) of cases (wider, n =
      7 or smaller, n = 3) while in 8/19 (42.1%) cases lesion borders were the same as
      delineated clinically as confirmed histologically. Thus, HIS is useful for the
      detection of subclinical LM/LMM borders.

PMID- 25394553
TI  - 'A great beneficial disease': colonial medicine and imperial authority in J.G.
      Farrell's The Siege of Krishnapur.
AB  - This article examines J. G. Farrell's depictions of colonial medicine as a means
      of analysing the historical reception of the further past and argues that the end
      of-Empire context of the 1970s in which Farrell was writing informed his
      reappraisal of Imperial authority with particular regard to the limits of medical
      knowledge and treatment. The article illustrates how in The Siege of Krishnapur
      (1973), Farrell repeatedly sought to challenge the authority of medical and
      colonial history by making direct use of period material in the construction of
      his fictional narrative; by using these sources with deliberate critical intent,
      Farrell directly engages with the received historical narrative of colonial
      India, that the British presence brought progress and development, particularly
      in matters relating to medicine and health. To support these assertions the paper
      examines how Farrell employed primary sources and period medical practices such
      as the nineteenth-century debate between miasma and waterborne Cholera
      transmission and the popularity of phrenology within his novels in order to cast
      doubt over and interrogate the British right to rule. Overall the paper will
      argue that Farrell's critique of colonial medical practices, apparently based on
      science and reason, was shaped by the political context of the 1970s and used to
      question the wider moral position of Empire throughout his fiction. 

PMID- 25394554
TI  - Neurogenesis in the septal and temporal part of the adult rat dentate gyrus.
AB  - Structural and functional dissociation between the septal and the temporal part
      of the dentate gyrus predispose for possible differentiations in the ongoing
      neurogenesis process of the adult hippocampus. In this study, BrdU-dated
      subpopulations of the rat septal and temporal dentate gyrus (coexpressing GFAP,
      DCX, NeuN, calretinin, calbindin, S100, caspase-3 or fractin) were quantified
      comparatively at 2, 5, 7, 14, 21, and 30 days after BrdU administration in order
      to examine the successive time-frames of the neurogenesis process, the glial or
      neuronal commitment of newborn cells and the occurring apoptotic cell death.
      Newborn neurons' migration from the neurogenic subgranular zone to the inner
      granular cell layer and expression of glutamate NMDA and AMPA receptors were also
      studied. BrdU immunocytochemistry revealed comparatively higher numbers of
      BrdU(+) cells in the septal part, but stereological analysis of newborn and total
      granule cells showed an identical ratio in the two parts, indicating an
      equivalent neurogenic ability, and a common topographical pattern along each
      part's longitudinal and transverse axis. Similarly, both parts exhibited
      extremely low levels of newborn glial and apoptotic cells. However, despite the
      initially equal division rate and pattern of the septal and temporal
      proliferating cells, their later proliferative profile diverged in the two parts.
      Dynamic differences in the differentiation, migration and maturation process of
      the two BrdU-incorporating subpopulations of newborn neurons were also detected,
      along with differences in their survival pattern. Therefore, we propose that
      various factors, including developmental date birth, local DG microenvironment
      and distinct functionality of the two parts may be the critical regulators of the
      ongoing neurogenesis process, leading the septal part to a continuous, rapid, and
      less-disciplined genesis rate, whereas the quiescent temporal microenvironment
      preserves a quite steady, less-demanding neurogenesis process.

PMID- 25394555
TI  - Improving the care of older persons in Australian prisons using the Policy Delphi
      method.
AB  - There are currently no internationally recognised and approved processes relating
      to the care of older persons with dementia in prison. This research aimed to
      develop tools and procedures related to managing the care of, including the
      identification and assessment of, older persons with dementia who are imprisoned
      in New South Wales, Australia. A modified approach to the Policy Delphi method,
      using both surveys and facilitated discussion groups, enabled experts to come
      together to discuss improving the quality of care provision for older persons
      with dementia in prison and achieve research aims. 

PMID- 25394556
TI  - The experience of family carers of people with dementia who are hospitalised.
AB  - Hospital admission of a person with dementia can have a significant impact on the
      family carer, who temporarily relinquishes caring to health professionals. A
      descriptive qualitative design using in-depth interviews with a conversational
      approach was used to elicit data. Adjusting to the change in the carer's role can
      be challenging and result in feelings of helplessness, loneliness, loss of
      control and being undervalued. Family support can assist with the transition but
      family conflict increases anxiety. Good communication between clinicians and the
      carer is vital. The carer should be included in decision-making as the 'expert'
      in the care of the person with dementia. This article discusses findings of a
      larger study specifically related to the emotional support required for the
      carers of people with dementia, who are admitted to hospital. The carer and the
      patient must be considered as a dyad in relation to discharge planning. 

PMID- 25394557
TI  - Abdominal compartment syndrome--the prevention and treatment of possible lethal
      complications following hip arthroscopy: a case report.
AB  - INTRODUCTION: Intra-abdominal hypertension and abdominal compartment syndrome
      have been increasingly recognized as a hip arthroscopy complication over the past
      decade. In the absence of consensus definitions and treatment guidelines, the
      diagnosis and management of intra-abdominal hypertension and abdominal
      compartment syndrome remains variable from institution to institution. CASE
      PRESENTATION: We report the occurrence of the extravasation of fluid into the
      abdomen during arthroscopic treatment of femoroacetabular impingement combined
      with resection of trochanteric bursa and our management of the condition in a 55
      year old Caucasian woman. CONCLUSIONS: We present an algorithm of treatment of
      abdominal compartment syndrome, as a hip arthroscopy complication, according to
      the consensus definitions and recommendations of the World Society of the
      Abdominal Compartment Syndrome. In the algorithm options, we have included
      paracentesis and percutaneous catheter decompression as the main point of
      treatment. Our algorithm will have a broader clinical impact on orthopedic
      surgery, anesthesiology and emergency medicine.

PMID- 25394558
TI  - Expression and anticancer activity analysis of recombinant human uPA1-43
      melittin.
AB  - The present study is focused on expression of a target fusion protein which can
      be used in ovarian cancer target therapy. It aimed to construct human urokinase
      type plasminogen activator (uPA)(1-43)-melittin eukaryotic expression vector to
      express recombinant human uPA(1-43)-melittin (rhuPA(1-43)-melittin) in P.
      pastoris and to detect its anticancer effects on ovarian cancer cells. The DNA
      sequences that encode uPA1-43 amino acids and melittin were synthesized according
      to its native amino acid sequences and consequently inserted into pPICZalphaC
      vector. Then uPA1-43-melittin -pPICZalphaC was transformed into P. pastoris X-33,
      and rhuPA(1-43)-melittin was expressed by methonal inducing. The bioactivities of
      recombinant fusion protein were detected with inhibition effects on growth of
      ovarian cancer cells, cell cycle detection and TUNEL assay. The results of DNA
      sequence analysis of the recombinant vector uPA(1-43)-melittin -pPICZalphaC
      demonstrated that the DNA encoding human uPA 1-43 amino acids and 1-26 amino
      acids of melittin was correctly inserted into the pPICZalphaC vector. After being
      induced by methonal, fusion protein with molecular weight 7.6 kDa was observed on
      the basis of SDS-PAGE and western blot analysis. The recombinant protein was able
      to suppress growth of SKOV3, induce cell cycle arrest and apoptosis of SKOV3
      cells. The fusion protein does not have any obvious toxicity on normal tissues.
      RhuPA(1-43)-melittin was successfully expressed in P. pastoris. Taking uPA(1-43)
      amino acids specifically binding to uPAR as targeted part of fusion protein, and
      making use of antitumor activity of melittin, the recombinant fusion protein it
      was able to inhibit growth of ovarian tumors and to be applied for effective
      targeted treatment.

PMID- 25394559
TI  - Assisting allied health in performance evaluation: a systematic review.
AB  - BACKGROUND: Performance evaluation raises several challenges to allied health
      practitioners and there is no agreed approach to measuring or monitoring allied
      health service performance. The aim of this review was to examine the literature
      on performance evaluation in healthcare to assist in the establishment of a
      framework that can guide the measurement and evaluation of allied health clinical
      service performance. This review determined the core elements of a performance
      evaluation system, tools for evaluating performance, and barriers to the
      implementation of performance evaluation. METHODS: A systematic review of the
      literature was undertaken. Five electronic databases were used to search for
      relevant articles: MEDLINE, Embase, CINAHL, PsychInfo, and Academic Search
      Premier. Articles which focussed on any allied health performance evaluation or
      those which examined performance in health care in general were considered in the
      review. Content analysis was used to synthesise the findings from individual
      articles. RESULTS: A total of 37 articles were included in the review. The
      literature suggests there are core elements involved in performance evaluation
      which include prioritising clinical areas for measurement, setting goals,
      selecting performance measures, identifying sources of feedback, undertaking
      performance measurement, and reporting the results to relevant stakeholders. The
      literature describes performance evaluation as multi-dimensional, requiring
      information or data from more than one perspective to provide a rich assessment
      of performance. A range of tools or instruments are available to capture various
      perspectives and gather a comprehensive picture of health care quality.
      CONCLUSIONS: Every allied health care delivery system has different performance
      needs and will therefore require different approaches. However, there are core
      processes that can be used as a framework to evaluate allied health performance.
      A careful examination of barriers to performance evaluation and subsequent
      tailoring of strategies to overcome these barriers should be undertaken to
      achieve the aims of performance evaluation. The findings of this review should
      inform the development of a standardised framework that can be used to measure
      and evaluate allied health performance. Future research should explore the
      utility and overall impact of such framework in allied health service delivery.

PMID- 25394560
TI  - Protective effect of carboxymethylated chitosan on hydrogen peroxide-induced
      apoptosis in nucleus pulposus cells.
AB  - Although the etiology of intervertebral disc degeneration is poorly understood,
      one approach to prevent this process may be to inhibit apoptosis. In the current
      study, the anti-apoptotic effects of carboxymethylated chitosan (CMCS) in nucleus
      pulposus (NP) cells were investigated with the aim to enhance disc cell survival.
      Rat NP cells were isolated and cultured in vitro, and hydrogen peroxide (H2O2)
      was used to build the NP cell apoptosis model. Cell viability was assessed with a
      cell counting kit-8 assay. The ratio of apoptotic cells was surveyed by annexin V
      fluorescein isothiocyanate (FITC) and propidium iodide (PI) double staining
      analysis, and the morphology was observed by Hoechst 33342 staining. The
      mitochondrial membrane potential of NP cells was evaluated by rhodamine 123
      fluorescence staining. Reverse transcription (RT)-quantitative polymerase chain
      reaction (qPCR) was performed to measure mRNA levels of inducible nitric oxide
      synthase (iNOS), caspase-3, B-cell lymphoma (Bcl)-2, type II collagen and
      aggrecan. Western blot analysis was performed to detect protein levels of iNOS
      and Bcl-2. The annexin V-FITC/PI and Hoechst 33342 staining results indicated
      that CMCS was able to prevent NP cells from apoptosis in a dose-dependent manner.
      Rhodamine 123 staining clarified that CMCS reduced the impairment of the
      mitochondrial membrane potential in H2O2-treated NP cells. Reduced caspase-3 and
      increased Bcl-2 activity were detected in CMCS-treated NP cells by RT-qPCR and
      western blot analysis. CMCS also promoted the proliferation and secretion of type
      II collagen and aggrecan in H2O2-treated NP cells. CMCS was indicated to be
      effective in preventing apoptotic cell death in vitro, demonstrating the
      potential advantages of this therapeutic approach in regulating disc
      degeneration.

PMID- 25394561
TI  - The relationship between the inflammatory response and cell adhesion on alginate
      chitosan-alginate microcapsules after transplantation.
AB  - Cell microencapsulation technology is a potential alternative therapy, but cell
      overgrowth and adhesion on the microcapsules after transplantation shortens their
      time of therapeutic efficacy. Inflammatory cells were the main cells that adhered
      to the microcapsules, so understanding the body's inflammatory processes would
      help to better identify the mechanisms of cell adhesion to the outer surface of
      the microcapsules. Our study measured the inflammatory cells and the cytokines
      and characterized the associated changes in the alginate-chitosan-alginate (ACA)
      microcapsules 1, 7, 14, and 28 days after implantation in the peritoneal cavity.
      Then the relationship between the inflammatory response and cell adhesion on the
      microcapsules was evaluated by multiple regression analysis. The results showed
      that the microcapsules did not evoke a systemic inflammatory response, but
      initiated a local inflammatory response in the peritoneal cavity. Furthermore,
      the correlation analysis showed that the level of cell adhesion on the
      microcapsules was related to the number of lymphocytes and macrophages, and the
      amount of IL-6, IL-10, and MCP-1 in the peritoneal cavity. Our results may
      provide a foundation for reducing the immune response to these microcapsules,
      prolonging graft survival and improving the efficacy of these treatments.

PMID- 25394562
TI  - Ethical issues experienced by mental health nurses in the administration of
      antipsychotic depot and long-acting intramuscular injections: a qualitative
      study.
AB  - The ethical issues experienced by mental health nurses in administering
      antipsychotic depot and long-acting intramuscular injections (LAI) were explored
      in the present study. Mental health nurses face ethically-difficult situations
      when administering these medications. A phenomenological research method guided
      by Max van Manen's human science approach describes and interprets the ethical
      issues involved in performing the procedure. Purposive and snowball sampling was
      used to select eight participants from two mental health hospitals.
      Semistructured interviews were carried out to collect data. A thematic analysis
      was conducted on the data. The four main themes that emerged from the analyses
      were: (i) lack of alternatives; (ii) safety; (iii) feeling uncomfortable; and
      (iv) difficulty maintaining the therapeutic relationship. The findings suggest
      that mental health nurses face ethical challenges in administering LAI. The
      findings raise much needed awareness of the need for mental health nurses and
      nurse educators to consider the ethical issues experienced while performing the
      procedure. There is a need for nurse education providers and organizations to
      provide opportunities for mental health nurses to address their 'lived
      experiences'. Educational courses are needed to equip mental health nurses with
      the technical and critical thinking skills to administer safe and effective
      antipsychotic depot and LAI. 

PMID- 25394563
TI  - Downregulation of Ras GTPase-activating protein 1 is associated with poor
      survival of breast invasive ductal carcinoma patients.
AB  - Ras GTPase-activating protein 1 (RASA1) functions to inactivate Ras-GTPase and
      inhibit the mitogenic signal. Reduction or loss of RASA1 expression occurs during
      human cancer development and progression. This study investigated RASA1
      expression in normal and breast cancer tissue specimens to determine the
      association with prognosis of breast cancer patients. Two sets of patient samples
      (45 fresh tissues and 373 paraffin-embedded tissues) were analyzed for RASA1
      expression using RT-qPCR and immunohisto-chemistry. The results showed that the
      expression of RASA1 mRNA was lower in breast cancer tissues than in the
      corresponding normal tissues (P<0.001). Additionally, RASA1 expression was
      reduced in 60.6% (226/373) of breast cancer tissues. The reduced RASA1 expression
      was significantly associated with tumor lymph node metastasis (P=0.002), advanced
      TNM stages (P=0.017), estrogen receptor (ER) expression (P=0.002), Ki-67
      (P=0.009), higher histological grade (P<0.001), and triple-negative breast cancer
      (P=0.041). Moreover, the reduced RASA1 expression was associated with shorter
      disease-free survival (P=0.036) and overall survival (P<0.001) of breast cancer
      patients. RASA1 expression, together with tumor lymph-node metastasis, TNM stage,
      Her-2 expression, and triple-negative breast cancer were independent factors in
      predicting survival of breast cancer patients. In conclusion, RASA1 expression is
      frequently reduced in breast cancer tissues, and the reduced RASA1 expression is
      associated with breast cancer progression and poor survival and disease-free
      survival of patients.

PMID- 25394564
TI  - "On-off-on" switchable sensor: a fluorescent spiropyran responds to extreme pH
      conditions and its bioimaging applications.
AB  - A novel spiropyran that responds to both extreme acid and extreme alkali and has
      an "on-off-on" switch is reported. Benzoic acid at the indole N-position and
      carboxyl group at the indole 6-position contribute to the extreme acid response.
      The ionizations of carboxyl and phenolic hydroxyl groups cause the extreme alkali
      response. Moreover, the fluorescent imaging in bacterial cells under extreme pH
      conditions supports the mechanism of pH response. 

PMID- 25394565
TI  - A regioselective synthesis of benzopinacolones through aerobic dehydrogenative
      alpha-arylation of the tertiary sp3 C-H bond of 1,1-diphenylketones with aromatic
      and heteroaromatic compounds.
AB  - A regioselective synthesis of symmetrical and unsymmetrical benzopinacolones
      through aerobic dehydrogenative alpha-arylation at the tertiary sp(3) C-H bond of
      substituted 1,1-diphenylketones with aromatic and heteroaromatic compounds, in
      the presence of K2S2O8 in CF3COOH at room temperature, is described. The reaction
      is proposed to go via a carbocation intermediate, which could be generated
      directly from cleavage of the sp(3) C-H bond of 1,1-diphenylketone. Subsequent
      alpha-arylation was achieved at the methene sp(3) carbon atom of the substituted
      ketone. A variety of substituted aromatic and heteroaromatic compounds were
      compatible with this reaction. In addition, benzopinacolones were converted into
      sterically hindered, tetrasubstituted alkenes and polycyclic aromatic compounds.

PMID- 25394566
TI  - Evaluation of genotype-phenotype relationships in patients referred for endocrine
      assessment in suspected Pendred syndrome.
AB  - DESIGN: Patients with Pendred syndrome have genotypic and phenotypic variability,
      leading to challenges in definitive diagnosis. Deaf children with enlarged
      vestibular aqueducts are often subjected to repeated investigations when tests
      for mutations in SLC26A4 are abnormal. This study provides genotype and phenotype
      information from patients with suspected Pendred syndrome referred to a single
      clinical endocrinology unit. METHODS: A retrospective analysis of 50 patients
      with suspected Pendred syndrome to investigate the correlation between genetic,
      perchlorate discharge test (PDT) and endocrine status. RESULTS: Eight patients
      with monoallelic SLC26A4 mutations had normal PDT. Of the 33 patients with
      biallelic mutations, ten of 12 patients with >30% discharge developed
      hypothyroidism. In our cohort, c.626G>T and c.3-2A>G result in milder clinical
      presentations with lower median perchlorate discharge of 9.3% (interquartile
      range 4-15%) compared with 40% (interquartile range 21-60%) for the remaining
      mutations. Eight novel mutations were detected. All patients with PDT <30%
      remained euthyroid to date, although the majority are still under the age of 30.
      There was a significant correlation between PDT and goitre size (R=0.61,
      P=0.0009) and the age of onset of hypothyroidism (R=-0.62, P=0.0297). In our
      population, the hazard of becoming hypothyroid increased by 7% per percentage
      point increase in PDT (P<0.001). CONCLUSION: There is a correlation between
      SLC26A4 genotype and thyroid phenotype. If results hold true for larger patient
      numbers and longer follow-up, then for patients with monoallelic mutations, PDT
      could be unnecessary. Patients with biallelic mutations and PDT discharge >30%
      have a high risk of developing goitre and hypothyroidism, and should have
      lifelong monitoring.

PMID- 25394567
TI  - Thyroid status and its association with cognitive functioning in healthy boys at
      10 years of age.
AB  - OBJECTIVE: Thyroid hormones (THs) are crucial for the correct maturation of the
      CNS and the neurodevelopment of the child. We aimed to investigate the
      association of TSH and free thyroxine (FT4) levels with cognitive functioning in
      children from the INMA-Granada cohort studied during their follow-up at the age
      of 9-11 years. DESIGN: We evaluated 300 children from the original cohort, which
      comprised 668 eligible mother-son pairs recruited at birth from 2000 to 2002 in
      Granada (Spain). METHODS: FT4 and TSH concentrations were measured, and cognitive
      development was assessed using neuropsychological tests (n=187). Children with
      chronic disease related to thyroid function and/or cognitive development were
      excluded. RESULTS: Median TSH and FT4 levels were 3.1 MUIU/ml and 1.2 ng/dl
      respectively. In multivariable regression analyses adjusted for maternal and
      child characteristics, children with TSH levels in the top tertile had worse
      verbal comprehension and immediate and long-term recall. Children with FT4 levels
      in the top tertile had better attention and lower impulsivity and were at a lower
      risk of scoring below the 20th percentile in intelligence quotient (OR=0.24; 95%
      CI=0.08-0.74; P=0.013) and in abstract reasoning ability (OR=0.28; 95% CI=0.09
      0.88; P=0.029). CONCLUSION: Our findings indicate that circulating THs and TSH
      may in the top tertile have an impact on cognitive functions; thus, higher TSH
      slightly but significantly increased the risk of a lower score in certain
      neuropsychological tests.

PMID- 25394568
TI  - Extreme synergistic mutational effects in the directed evolution of a baeyer
      villiger monooxygenase as catalyst for asymmetric sulfoxidation.
AB  - Structure-based directed evolution utilizing iterative saturation mutagenesis
      (ISM) has been applied to phenyl acetone monooxygenase (PAMO), a thermally robust
      Baeyer-Villiger monooxygenase, in the quest to access a mutant which displays
      reversed enantioselectivity in the asymmetric sulfoxidation of prochiral
      thioethers. Whereas WT PAMO leads to 90% ee in the sulfoxidation of p
      methylbenzyl methyl thioether with preference for the (S)-sulfoxide, the evolved
      mutant I67Q/P440F/A442N/L443I is 95% (R)-selective in the reaction of this and
      other thioethers. Partial deconvolution of the (R)-selective mutant with
      generation of the respective four single mutants shows that all of them are (S)
      selective, which points to pronounced synergism (cooperative nonadditivity) when
      they interact in concert. Complete deconvolution with formation of all
      combinatorial forms of the respective double and triple mutants allows the
      designed construction of a fitness landscape featuring all 24 upward pathways
      leading from WT to the (R)-selective quadruple mutant. In all 24 trajectories
      strong cooperative mutational effects were found as well, which indicates that
      such mutational changes in enzymes constitute nonlinear systems. A theoretical
      analysis based on induced fit docking explains many of the observed effects on a
      molecular level. 

PMID- 25394569
TI  - Congenital talipes equinovarus: frequency of associated malformations not
      identified by prenatal ultrasound.
AB  - OBJECTIVES: To establish the frequency of prenatally undetected associated
      malformations (identified at birth) in infants with apparent "isolated" club foot
      deformity. METHODS: A cohort study of all infants with unilateral or bilateral
      club foot deformity identified at birth among 311 480 infants surveyed between
      1972 and 2012 at Brigham and Women's Hospital in Boston. Those with talipes
      equinovarus were divided into "isolated" and "complex", based on the findings in
      examination and by chromosome analysis. RESULTS: One hundred and forty-two
      infants had "isolated" talipes equinovarus (TEV), and 66 had the "complex" type.
      Six (4.2%) of the 142 infants with "isolated" TEV were found at birth to have
      associated malformations that had not been identified by imaging during
      pregnancy. These abnormalities included hip dislocation (n = 2), bilateral post
      axial polydactyly of the feet (n = 1), penile chordee (n = 1), and hypospadias (n
      = 2). CONCLUSION: In this consecutive series of infants with isolated talipes
      equinovarus, 95.8% had no additional malformations identified by examination at
      birth. None of the additional findings were severe enough to affect the medical
      prognosis of the affected infant. (c) 2014 John Wiley & Sons, Ltd.

PMID- 25394570
TI  - Low-temperature N2 binding to two-coordinate L2Fe(0) enables reductive trapping
      of L2FeN2(-) and NH3 generation.
AB  - The two-coordinate [(CAAC)2Fe] complex [CAAC = cyclic (alkyl)(amino)carbene]
      binds dinitrogen at low temperature (T<-80  degrees C). The resulting putative
      three-coordinate N2 complex, [(CAAC)2Fe(N2)], was trapped by one-electron
      reduction to its corresponding anion [(CAAC)2FeN2](-) at low temperature. This
      complex was structurally characterized and features an activated dinitrogen unit
      which can be silylated at the beta-nitrogen atom. The redox-linked complexes
      [(CAAC)2Fe(I)][BAr(F)4], [(CAAC)2Fe(0)], and [(CAAC)2Fe(-I)N2](-) were all found
      to be active for the reduction of dinitrogen to ammonia upon treatment with KC8
      and HBAr(F)4?2 Et2O at -95  degrees C [up to (3.4+/-1.0) equivalents of ammonia
      per Fe center]. The N2 reduction activity is highly temperature dependent, with
      significant N2 reduction to NH3 only occurring below -78  degrees C. This
      reactivity profile tracks with the low temperatures needed for N2 binding and an
      otherwise unavailable electron-transfer step to generate reactive [(CAAC)2FeN2](
      ) .

PMID- 25394571
TI  - Potential long term vaccine benefits poorly translate in cost effectiveness
      modelling.

PMID- 25394572
TI  - Penguins significantly increased phosphine formation and phosphorus contribution
      in maritime Antarctic soils.
AB  - Most studies on phosphorus cycle in the natural environment focused on
      phosphates, with limited data available for the reduced phosphine (PH3). In this
      paper, matrix-bound phosphine (MBP), gaseous phosphine fluxes and phosphorus
      fractions in the soils were investigated from a penguin colony, a seal colony and
      the adjacent animal-lacking tundra and background sites. The MBP levels (mean
      200.3 ng kg(-1)) in penguin colony soils were much higher than those in seal
      colony soils, animal-lacking tundra soils and the background soils. Field PH3
      flux observation and laboratory incubation experiments confirmed that penguin
      colony soils produced much higher PH3 emissions than seal colony soils and animal
      lacking tundra soils. Overall high MBP levels and PH3 emissions were modulated by
      soil biogeochemical processes associated with penguin activities: sufficient
      supply of the nutrients phosphorus, nitrogen, and organic carbon from penguin
      guano, high soil bacterial abundance and phosphatase activity. It was proposed
      that organic or inorganic phosphorus compounds from penguin guano or seal excreta
      could be reduced to PH3 in the Antarctic soils through the bacterial activity.
      Our results indicated that penguin activity significantly increased soil
      phosphine formation and phosphorus contribution, thus played an important role in
      phosphorus cycle in terrestrial ecosystems of maritime Antarctica.

PMID- 25394573
TI  - Can we use viral kinetic models to individualize treatment?

PMID- 25394574
TI  - Real-time estimation and biofeedback of single-neuron firing rates using local
      field potentials.
AB  - The long-term stability and low-frequency composition of local field potentials
      (LFPs) offer important advantages for robust and efficient neuroprostheses.
      However, cortical LFPs recorded by multi-electrode arrays are often assumed to
      contain only redundant information arising from the activity of large neuronal
      populations. Here we show that multichannel LFPs in monkey motor cortex each
      contain a slightly different mixture of distinctive slow potentials that
      accompany neuronal firing. As a result, the firing rates of individual neurons
      can be estimated with surprising accuracy. We implemented this method in a real
      time biofeedback brain-machine interface, and found that monkeys could learn to
      modulate the activity of arbitrary neurons using feedback derived solely from
      LFPs. These findings provide a principled method for monitoring individual
      neurons without long-term recording of action potentials. 

PMID- 25394576
TI  - [Hyponatremia: differential diagnosis and therapy].
AB  - Hyponatremia is the most commonly occurring electrolyte disorder and is
      associated with increased morbidity and mortality-independent of the underlying
      disease. Despite its high prevalence, hyponatremia is often underestimated and
      inadequately addressed in clinical routine. Depending on disease stage and
      severity, the electrolyte disorder can present with a wide spectrum of
      neurological signs and symptoms, ranging from adynamia and gait disturbances, to
      syncope or coma. While the underlying causes of hyponatremia may be manifold,
      their identification is crucial to initiating adequate therapeutic measures for
      symptomatic and causal therapy. The syndrome of inappropriate antidiuretic
      hormone (ADH) secretion (SiADH) is the most common cause of hyponatremia, present
      in 1/3 of hyponatremic patients and usually a result of medication, neurological,
      respiratory or malignant disease. A differential diagnostic approach using a
      simple algorithm that includes clinical and laboratory parameters is essential
      for identifying the underlying cause of hyponatremia and administering goal
      directed therapy. The development of vaptans has provided new options in the
      treatment of SiADH-associated hyponatremia.

PMID- 25394577
TI  - [Commentary to the article "Should a cardioverter-defibrillator be implanted in
      an Andersen-Tawil syndrome patient with severe ventricular arrhythmias and
      syncope?"].

PMID- 25394578
TI  - Circulating androgens are associated with mood disturbances in young
      postmenopausal women.
AB  - OBJECTIVES: We aimed to evaluate the association between circulating androgens
      and the presence of psychological symptoms in a sample of healthy middle-aged
      women. METHODS: Psychological and depressive symptoms were evaluated in a total
      of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the
      Zung Depression Scale, respectively. We investigated the associations between the
      SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well
      as serum levels of androgens. RESULTS: The free androgen index was positively
      associated with scores of depression (b-coefficient +/- standard error (SE) = 0.2
      +/- 0.2, p = 0.040), anxiety (b-coefficient +/- SE = 0.2 +/- 0.2, p = 0.028),
      anger/aggressiveness (b-coefficient +/- SE = 0.3 +/- 0.2, p = 0.026), psychotism
      (b-coefficient +/- SE = 0.3 +/- 0.1, p = 0.013) as well as with the global index
      of the SCL-90R scale (b-coefficient +/- SE = 0.2 +/- 0.1, p = 0.036), while sex
      hormone binding globulin was negatively associated with depression (b-coefficient
      +/- SE = -0.2 +/- 0.0, p = 0.046) and psychotism (b-coefficient +/- SE = -0.2 +/-
      0.0, p = 0.047). These associations were independent of vasomotor symptomatology,
      smoking and hormone therapy intake and were more pronounced in younger (<= 5.5
      years) compared to older postmenopausal women. Levels of dehydroepiandrosterone
      sulfate were positively associated with interpersonal sensitivity (b-coefficient
      +/- SE = 0.3 +/- 0.3, p = 0.042), psychotism (b-coefficient +/- SE = 0.4 +/- 0.2,
      p = 0.007) and the global index (b-coefficient +/- SE = 0.3 +/- 0.2, p = 0.040)
      in women < 5.5 years postmenopausal. No significant associations were observed
      between the Zung or Greene Scale scores and levels of androgens. CONCLUSION:
      Higher androgenicity was positively associated with symptoms of anxiety and
      depression in postmenopausal women. These associations were stronger in women
      closer to the menopausal transition, a finding which may suggest that menopause
      rather than aging may mediate the association of androgens with mood disorders.

PMID- 25394579
TI  - Nasal IL-17F is related to bronchial IL-17F/neutrophilia and exacerbations in
      stable atopic severe asthma.
AB  - Severe asthma (SA) is associated with neutrophil recruitment and T helper (TH )17
      chemokine overexpression in bronchial biopsies. We aimed to evaluate IL-17A and
      IL-17F expression in nasal/bronchial lamina propria of atopic mild-to-severe
      asthmatics and controls in relation to neutrophilia and asthma exacerbations.
      Cryostat sections of nasal/bronchial biopsies obtained from 14 SA and 14 mild
      asthma (MA) stable atopic patients with rhinitis, and seven healthy controls were
      analyzed by immunohistochemistry for neutrophils, IL-17A and IL-17F expression.
      Atopic SA showed an increase in asthma exacerbations number, IL-17F and IL-17A
      expression in nasal/bronchial lamina propria compared to MA and controls, and a
      higher expression of bronchial neutrophils in SA compared to MA and controls. In
      all asthmatics, significant relationships were found between bronchial IL-17F and
      neutrophils/FEV1 , nasal IL-17F and bronchial neutrophil/IL-17 markers and
      between the latter and exacerbations, suggesting that nasal IL-17F might be
      informative on bronchial IL17-driven neutrophilia in atopic SA. 

PMID- 25394582
TI  - Effects of sumatriptan nasal spray (Imigran) on isolated rat's tracheal smooth
      muscle.
AB  - Sumatriptan (Imigran) is a potent and highly selective 5-HT1 receptor agonist
      often used in treating acute migraine. Intranasal sumatriptan is well absorbed
      and is generally effective in relieving headache. However, the effects of Imigran
      given intratracheally have rarely been well explored. We aimed to verify the
      effect of Imigran, which acts on the tracheal smooth muscle directly in vitro. We
      examined the effectiveness of Imigran on isolated rat tracheal smooth muscle by
      testing: (1) effect on tracheal smooth muscle resting tension; (2) effect on
      contraction caused by 10(-6) M methacholine as a parasympathetic mimetic; (3)
      effect of the drugs on electrically induced tracheal smooth muscle contractions.
      The results indicated that the addition of methacholine to the incubation medium
      caused the trachea to contract in a dose-dependent manner. The addition of
      Imigran at doses of 10(-5) M or above elicited a significant relaxation response
      to 10(-6) M methacholine-induced contraction. Imigran could inhibit electrical
      field stimulation-induced spike contraction. It also had a minimal effect on the
      basal tension of trachea as the concentration increased. The study indicated high
      concentrations of Imigran could cause bronchodilation to reduce asthma attacks
      not only by blocking parasympathetic tone, but also by directly antagonizing the
      effect of cholinergic receptors.

PMID- 25394583
TI  - Chromosome landmarks and autosome-sex chromosome translocations in Rumex
      hastatulus, a plant with XX/XY1Y2 sex chromosome system.
AB  - Rumex hastatulus is the North American endemic dioecious plant with heteromorphic
      sex chromosomes. It is differentiated into two chromosomal races: Texas (T) race
      characterised by a simple XX/XY sex chromosome system and North Carolina (NC)
      race with a polymorphic XX/XY1Y2 sex chromosome system. The gross karyotype
      morphology in NC race resembles the derived type, but chromosomal changes that
      occurred during its evolution are poorly understood. Our C-banding/DAPI and
      fluorescence in situ hybridization (FISH) experiments demonstrated that Y
      chromosomes of both races are enriched in DAPI-positive sequences and that the
      emergence of polymorphic sex chromosome system was accompanied by the break of
      ancestral Y chromosome and switch in the localization of 5S rDNA, from autosomes
      to sex chromosomes (X and Y2). Two contrasting domains were detected within North
      Carolina Y chromosomes: the older, highly heterochromatinised, inherited from the
      original Y chromosome and the younger, euchromatic, representing translocated
      autosomal material. The flow-cytometric DNA estimation showed ~3.5 % genome
      downsizing in the North Carolina race. Our results are in contradiction to
      earlier reports on the lack of heterochromatin within Y chromosomes of this
      species and enable unambiguous identification of autosomes involved in the
      autosome-heterosome translocation, providing useful chromosome landmarks for
      further studies on the karyotype and sex chromosome differentiation in this
      species. 

PMID- 25394580
TI  - Biochemical markers for assessment of calcium economy and bone metabolism:
      application in clinical trials from pharmaceutical agents to nutritional
      products.
AB  - Nutrition plays an important role in osteoporosis prevention and treatment.
      Substantial progress in both laboratory analyses and clinical use of biochemical
      markers has modified the strategy of anti-osteoporotic drug development. The
      present review examines the use of biochemical markers in clinical research aimed
      at characterising the influence of foods or nutrients on bone metabolism. The two
      types of markers are: (i) specific hormonal factors related to bone; and (ii)
      bone turnover markers (BTM) that reflect bone cell metabolism. Of the former,
      vitamin D metabolites, parathyroid hormone, and insulin-like growth factor-I
      indicate responses to variations in the supply of bone-related nutrients, such as
      vitamin D, Ca, inorganic phosphate and protein. Thus modification in bone
      remodelling, the key process upon which both pharmaceutical agents and nutrients
      exert their anti-catabolic or anabolic actions, is revealed. Circulating BTM
      reflect either osteoclastic resorption or osteoblastic formation. Intervention
      with pharmacological agents showed that early changes in BTM predicted bone loss
      and subsequent osteoporotic fracture risk. New trials have documented the
      influence of nutrition on bone-tropic hormonal factors and BTM in adults,
      including situations of body-weight change, such as anorexia nervosa, and weight
      loss by obese subjects. In osteoporosis-prevention studies involving dietary
      manipulation, randomised cross-over trials are best suited to evaluate influences
      on bone metabolism, and insight into effects on bone metabolism may be gained
      within a relatively short time when biochemical markers are monitored. 

PMID- 25394584
TI  - Treatment satisfaction of patients with psoriasis.
AB  - Treatment satisfaction of patients with psoriasis largely depends on the
      treatment modality, but evidence on preferences for specific medications is
      scarce. Here we assessed treatment satisfaction of 200 participants with moderate
      to-severe psoriasis from a German University hospital with a 5-point scale and
      the Treatment Satisfaction Questionnaire for Medication (TSQM) and determined
      sociodemographic and disease-related influence factors. Participants obtaining
      biologicals and traditional systemic medications were significantly more
      satisfied than those receiving phototherapy or topical agents (TSQM = 323.3,
      288.0, 260.6 or 266.8; p < 0.001). The highest TSQM score was calculated for
      ustekinumab (350.1), followed by acitretin (338.1), adalimumab (323.0), fumaric
      acid esters (304.7), infliximab (300.2), etanercept (298.8), and methotrexate
      (272.3; p < 0.001). High disease-related quality of life impairment (beta = 
      0.437, p < 0.001) and psoriatic arthritis (beta = -0.185, p = 0.005) were
      associated with decreased satisfaction. Optimising satisfaction is essential to
      improve adherence and outcome. We show high preferences for biologicals,
      particularly ustekinumab, but also good satisfaction with certain traditional
      medications.

PMID- 25394585
TI  - Gender difference in acquired seizure susceptibility in adult rats after early
      complex febrile seizures.
AB  - Gender differences are involved in many neurological disorders including
      epilepsy. However, little is known about the effect of gender difference on the
      risk of epilepsy in adults with a specific early pathological state such as
      complex febrile seizures (FSs) in infancy. Here we used a well-established
      complex FS model in rats and showed that: (1) the susceptibility to seizures
      induced by hyperthermia, pentylenetetrazol (PTZ), and maximal electroshock (MES)
      was similar in male and female rat pups, while males were more susceptible to PTZ
      and MES-induced seizures than age-matched females in normal adult rats; (2)
      adult rats with complex FSs in infancy acquired higher seizure susceptibility
      than normal rats; importantly, female FS rats were more susceptible to PTZ and
      MES than male FS rats; and (3) the protein expression of interleukin-1beta, an
      inflammatory factor associated with seizure susceptibility, was higher in adult
      FS females than in males, which may reflect a gender-difference phenomenon of
      seizure susceptibility. Our results provide direct evidence that the acquired
      seizure susceptibility after complex FSs is gender-dependent.

PMID- 25394586
TI  - Ultrasound evaluation of visceral and subcutaneous fat reduction in morbidly
      obese subjects undergoing laparoscopic gastric banding, sleeve gastrectomy, and
      Roux-en-Y gastric bypass: a prospective comparison study.
AB  - BACKGROUND: Visceral fat (VF) plays a major role in the development of metabolic
      syndrome associated with obesity. The aim of our study is to compare VF and
      subcutaneous fat (SCF) reduction measured by ultrasonography (US) after
      laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy
      (LSG), and laparoscopic Roux-En-Y gastric bypass (LRYGB). METHODS: Thirty-nine
      morbidly obese patients were prospectively evaluated by US before surgery and 3,
      6, and 12 months following surgery to determine VF and SCF thickness. RESULTS:
      Three statistically comparable groups of morbidly obese patients underwent LRYGB
      (n = 13), LSG (n = 15), and LAGB (n = 11). The three groups did not differ in
      initial age, gender, body mass index (BMI), VF, or SCF. Final excess weight loss
      (EWL%) was highest after LSG and LRYGB followed by LAGB (81 +/- 5.8 vs. 69.5 +/-
      4.5 vs. 43.4 +/- 5.2, p < 0.001). LSG and LRYGB were significantly more efficient
      in VF reduction (DeltaVF) compared with LAGB (7.1 +/- 0.5 vs. 5.6 +/- 0.6 vs. 3.6
      +/- 0.8, p = 0.004). SCF reduction (DeltaSCF) was also highest after LSG followed
      by LRYGB and LAGB (3 +/- 0.2 vs. 2.2 +/- 0.4 vs. 1.9 +/- 0.4, p = 0.08). The
      change in fat distribution, determined as Delta(VF/SCF), showed a preferential VF
      reduction in the LSG and LRYGB patients compared with patients that underwent
      LAGB (0.59 +/- 0.1 vs. 0.52 +/- 0.2 vs. 0.19 +/- 0.2, p = 0.42). In a subgroup
      analysis comparing only LSG to LRYGB, no statistically significant difference was
      seen in EWL%, DeltaVF, DeltaSCF, or in fat distribution Delta(VF/SCF).
      CONCLUSION: LSG and LRYGB show better preferential and overall VF reduction than
      LAGB. US may serve as a simple tool of evaluating postoperative fat distribution.

PMID- 25394587
TI  - Comparability of weight loss reporting after gastric bypass and sleeve
      gastrectomy using BOLD data 2008-2011.
AB  - BACKGROUND: Weight loss after bariatric surgery is commonly reported as either a
      percentage of initial body weight (%IBW) or 100% minus %IBW which is a percentage
      of total weight loss (%TWL). These are basically equivalent expressions. Weight
      loss is also reported as %EWL or as a percentage of excess body mass index loss
      (%EBMIL). These last two expressions incorporate the concepts of ideal body
      weight and BMI = 25 as reference points. More straightforward but less commonly
      used is absolute weight loss. This study compares these various measures using
      the Bariatric Outcomes Longitudinal Database (BOLD). METHODS: BOLD data, 2008
      2011, was accessed for outcomes on 239,659 gastric bypass (GB) and sleeve
      gastrectomy (SG) patients with approval of the Surgical Review Corporation. The
      outcome data was converted into %TWL, %EWL, and %EBMIL. %EBMIL was varied by
      changing the reference BMI from 1 to 25 kg/m(2). The post operation data was
      analyzed for both procedures. Variation coefficients (VC) were compared using
      different measurements on the same data pool. We assumed that the lesser the
      variation, the more reliable the measure is, and therefore, we made use of the VC
      to compare the different reporting methods. RESULTS: There were 164,247 patients
      who remained after removal of errors and missing data. Demographics are as
      follows: 78.1% female, 73.1% white, 12.5% black, 8.71% Hispanic, 81.6% GB, 18.4%
      SG, mean age of 44.8 years, height of 167.0 cm, weight of 132.0 kg, and BMI of
      47.1 kg/m(2). GB patients had 26.8%TWL at 6 months (VC = 21.5) and 34.2%TWL at 12
      months (VC = 27.0). %EWL was 54.7 at 6 months (VC = 27.3) and 69.4 at 12 months
      (VC = 30.9). Varying the reference BMI for %EBMIL showed the lowest VC to be 0-2
      kg/m(2) for GB up to 12 months post operation. SG patients had 24.0%TWL at 6
      months (VC = 25.4) and 29.5 at 12 months (VC = 30.5). %EWL was 50.0% at 6 months
      (VC = 31.4) and 60.2% at 12 months (VC = 34.5). Varying the reference BMI for
      %EBMIL showed that the lowest VC occurred when the reference weight was chosen as
      0 kg/m(2) for both GB and SG. %TWL or, equivalently, %IBW had the lowest
      variation coefficient and therefore is the more accurate measure of weight loss
      following bariatric surgery. CONCLUSIONS: For ease and accuracy of comparison,
      the percentage of initial body weight or percentage of total weight loss should
      be used for the expression of weight loss after surgery.

PMID- 25394588
TI  - Prevalence of anemia and related deficiencies 10 years after gastric bypass--a
      retrospective study.
AB  - BACKGROUND: Bariatric surgery has gained wide acceptance as treatment for severe
      obesity and is associated with decreased overall mortality. The aims of this
      study were to evaluate the prevalence of anemia long term after Roux-en-Y gastric
      bypass (RYGB) and to search for factors predicting anemia. METHODS: All 745
      patients who underwent RYGB between 1993 and 2003 at either Orebro or Uppsala
      University Hospital and who were living in Sweden were invited to participate by
      providing a fasting blood sample and completing a questionnaire about their
      health status. Full blood count, serum iron, transferrin, vitamin B12, and folic
      acid were determined. RESULTS: Follow-up was completed in 431 patients (58 %)
      with mean age 51.3 +/- 10 years. Of all patients, 27 % had anemia postoperatively
      and related deficiencies; iron, folic acid, and vitamin B12 were seen in 20, 12,
      and 2 %, respectively. There was no correlation between anemia and sex, follow-up
      time, 25-OH vitamin D level, and preoperative or postoperative BMI. An inverse
      correlation was found between anemia and regular medical checkups concerning
      gastric bypass surgery. CONCLUSION: Twenty-seven percent of patients had anemia
      more than 10 years after RYGB. Anemia does not seem to progress with time and was
      less common in patients with regular medical checkups. Thus, improved long-term
      follow-up is needed.

PMID- 25394589
TI  - Technique evolution, learning curve, and outcomes of 200 robot-assisted gastric
      bypass procedures: a 5-year experience.
AB  - BACKGROUND: We evaluate our 5-year experience, evolution of technique, and
      clinical outcomes with robot-assisted RYGB. METHODS: Two hundred consecutive
      patients who underwent robot-assisted RYGB at our center were included. Among
      them, 118 patients underwent a hybrid robot-assisted laparoscopic RYGB (LRRYGB),
      and 82 patients underwent a totally robotic RYGB (TRRYGB). Patient demographics,
      clinical characteristics, comorbidities, operative parameters, conversions,
      morbidity, mortality, and excess weight loss were analyzed. RESULTS: Most of the
      patients (88 %) were female with a mean age of 41.9 years and mean BMI of 46.6
      kg/m(2). The outcomes of patients who underwent LRRYGB (n = 118) were compared to
      those who underwent TRRYGB (n = 82). The mean operative time in TRRYGB group was
      170.9 +/- 51.4 min which was significantly lower than LRRYGB group (216 +/- 54.1
      min). The mean operative time for the last 100 patients was significantly lower
      than that for the first 100 patients. The excess weight loss (EWL) was 58.3 % at
      6 months, 67.7 % at 1 year, 71.6 % at 2 years, and 65 % at 3 years. There were
      three conversions to open, three reoperations and four readmissions. There were
      no anastomotic leak, major bleed, gastrojejunostomy stricture, or mortality seen
      in our series. CONCLUSIONS: Use of robot assistance to perform RYGB is safe and
      may reduce the associated complications, namely, anastomotic leak,
      gastrojejunostomy (GJ) stricture, and hemorrhage. Excess weight loss at 2 years
      after RRYGB is comparable to laparoscopic RYGB.

PMID- 25394590
TI  - Aortic dissection during rivaroxaban therapy: a challenging care.

PMID- 25394591
TI  - The impact of cleft lip and palate repair on maxillofacial growth.
AB  - Surgical correction is central to current team-approached cleft treatment. Cleft
      surgeons are always concerned about the impact of their surgical maneuver on the
      growth of the maxilla. Hypoplastic maxilla, concaved mid-face and deformed dental
      arch have constantly been reported after cleft treatments. It is very hard to
      completely circumvent these postoperative complications by current surgical
      protocols. In this paper, we discussed the factors that inhibit the maxillofacial
      growth on cleft patients. These factors included pre-surgical intervention, the
      timing of cleft palate and alveolae repair, surgical design and treatment
      protocol. Also, we made a review about the influence on the maxillary growth in
      un-operated cleft patients. On the basis of previous researches, we can conclude
      that most of scholars express identity of views in these aspects: early
      palatoplasty lead to maxilla growth inhibition in all dimensions; secondary
      alveolar bone graft had no influence on maxilla sagittal growth; cleft lip repair
      inhibited maxilla sagittal length in patients with cleft lip and palate; Veau's
      pushback palatoplasty and Langenbeck's palatoplasty with relaxing incisions were
      most detrimental to growth; Furlow palatoplasty showed little detrimental effect
      on maxilla growth; timing of hard palate closure, instead of the sequence of hard
      or soft palate repair, determined the postoperative growth. Still, scholars hold
      controversial viewpoints in some issues, for example, un-operated clefts have
      normal growth potential or not, pre-surgical intervention and pharyngoplasty
      inhibited maxillofacial growth or not. 

PMID- 25394592
TI  - Chlorogenic acid alters the voltage-gated potassium channel currents of
      trigeminal ganglion neurons.
AB  - Chlorogenic acid (5-caffeoylquinic acid, CGA) is a phenolic compound that is
      found ubiquitously in plants, fruits and vegetables and is formed via the
      esterification of caffeic acid and quinic acid. In addition to its notable
      biological functions against cardiovascular diseases, type-2 diabetes and
      inflammatory conditions, CGA was recently hypothesized to be an alternative for
      the treatment of neurological diseases such as Alzheimer's disease and
      neuropathic pain disorders. However, its mechanism of action is unclear. Voltage
      gated potassium channel (Kv) is a crucial factor in the electro-physiological
      processes of sensory neurons. Kv has also been identified as a potential
      therapeutic target for inflammation and neuropathic pain disorders. In this
      study, we analysed the effects of CGA on the two main subtypes of Kv in
      trigeminal ganglion neurons, namely, the IK,A and IK,V channels. Trigeminal
      ganglion (TRG) neurons were acutely disassociated from the rat TRG, and two
      different doses of CGA (0.2 and 1 mmol?L(-1)) were applied to the cells. Whole
      cell patch-clamp recordings were performed to observe alterations in the
      activation and inactivation properties of the IK,A and IK,V channels. The results
      demonstrated that 0.2 mmol?L(-1) CGA decreased the peak current density of IK,A.
      Both 0.2 mmol?L(-1) and 1 mmol?L(-1) CGA also caused a significant reduction in
      the activation and inactivation thresholds of IK,A and IK,V. CGA exhibited a
      strong effect on the activation and inactivation velocities of IK,A and IK,V.
      These findings provide novel evidence explaining the biological effects of CGA,
      especially regarding its neurological effects. 

PMID- 25394593
TI  - Bivalent histone modifications during tooth development.
AB  - Histone methylation is one of the most widely studied post-transcriptional
      modifications. It is thought to be an important epigenetic event that is closely
      associated with cell fate determination and differentiation. To explore the
      spatiotemporal expression of histone H3 lysine 4 trimethylation (H3K4me3) and
      histone H3 lysine 27 trimethylation (H3K27me3) epigenetic marks and methylation
      or demethylation transferases in tooth organ development, we measured the
      expression of SET7, EZH2, KDM5B and JMJD3 via immunohistochemistry and
      quantitative polymerase chain reaction (qPCR) analysis in the first molar of
      BALB/c mice embryos at E13.5, E15.5, E17.5, P0 and P3, respectively. We also
      measured the expression of H3K4me3 and H3K27me3 with immunofluorescence staining.
      During murine tooth germ development, methylation or demethylation transferases
      were expressed in a spatial-temporal manner. The bivalent modification
      characterized by H3K4me3 and H3K27me3 can be found during the tooth germ
      development, as shown by immunofluorescence. The expression of SET7, EZH2 as
      methylation transferases and KDM5B and JMJD3 as demethylation transferases
      indicated accordingly with the expression of H3K4me3 and H3K27me3 respectively to
      some extent. The bivalent histone may play a critical role in tooth organ
      development via the regulation of cell differentiation. 

PMID- 25394594
TI  - Evaluation of a thermoprotective gel for hydrodissection during percutaneous
      microwave ablation: in vivo results.
AB  - PURPOSE: To evaluate whether thermoreversible poloxamer 407 15.4 % in water
      (P407) can protect non-target tissues adjacent to microwave (MW) ablation zones
      in a porcine model. MATERIALS AND METHODS: MW ablation antennas were placed
      percutaneously into peripheral liver, spleen, or kidney (target tissues) under US
      and CT guidance in five swine such that the expected ablation zones would extend
      into adjacent diaphragm, body wall, or bowel (non-target tissues). For
      experimental ablations, P407 (a hydrogel that transitions from liquid at room
      temperature to semi-solid at body temperature) was injected into the potential
      space between target and non-target tissues, and the presence of a gel barrier
      was verified on CT. No barrier was used for controls. MW ablation was performed
      at 65 W for 5 min. Thermal damage to target and non-target tissues was evaluated
      at dissection. RESULTS: Antennas were placed 7 +/- 3 mm from the organ surface
      for both control and gel-protected ablations (p = 0.95). The volume of gel
      deployed was 49 +/- 27 mL, resulting in a barrier thickness of 0.8 +/- 0.5 cm.
      Ablations extended into non-target tissues in 12/14 control ablations (mean
      surface area = 3.8 cm(2)) but only 4/14 gel-protected ablations (mean surface
      area = 0.2 cm(2); p = 0.0005). The gel barrier remained stable at the injection
      site throughout power delivery. CONCLUSION: When used as a hydrodissection
      material, P407 protected non-targeted tissues and was successfully maintained at
      the injection site for the duration of power application. Continued
      investigations to aid clinical translation appear warranted.

PMID- 25394595
TI  - Percutaneous lung thermal ablation of non-surgical clinical N0 non-small cell
      lung cancer: results of eight years' experience in 87 patients from two centers.
AB  - PURPOSE: To evaluate the survival outcomes of percutaneous thermal ablation (RFA
      + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC)
      ineligible for surgery. MATERIALS AND METHODS: Eighty-seven patients from two
      comprehensive cancer centers were included. Eighty-two patients were treated with
      RFA electrodes and five with microwave antenna. Overall survival (OS) and disease
      free survival (DFS) were estimated and predictive factors of local tumor
      progression, OS and DFS identified and compared by univariate and multivariate
      analyses RESULTS: Median follow-up was 30.5 months (interquartile range 16.7-51)
      and tumor size was 21 mm (range 10-54 mm). Treatment was incomplete for 14
      patients with a local tumor progression of 11.5, 18.3, and 21.1 % at 1, 2, and 3
      years, respectively. Two patients presented with neurological (grade III or IV)
      complications, and one died of respiratory and multivisceral failure as a result
      of the procedure at 29 days. In univariate analysis, increasing tumor size (P =
      0.003) was the only predictive factor related to risk of local tumor progression.
      5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology
      (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In
      multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032)
      were independent prognostic factors for DFS. CONCLUSIONS: Oversized and
      overlapping ablation of N0 NSCLC was well tolerated, effective, with few local
      tumor progressions, even over long-term follow-up. Increasing tumor size was the
      main prognostic factor linked to OS, DFS, and local tumor progression.

PMID- 25394597
TI  - CLAD: does the Emperor have new clothes?

PMID- 25394596
TI  - Update of the trauma risk adjustment model of the TraumaRegister DGUTM: the
      Revised Injury Severity Classification, version II.
AB  - INTRODUCTION: The TraumaRegister DGUTM (TR-DGU) has used the Revised Injury
      Severity Classification (RISC) score for outcome adjustment since 2003. In recent
      years, however, the observed mortality rate has fallen to about 2% below the
      prognosis, and it was felt that further prognostic factors, like pupil size and
      reaction, should be included as well. Finally, an increasing number of cases did
      not receive a RISC prognosis due to the missing values. Therefore, there was a
      need for an updated model for risk of death prediction in severely injured
      patients to be developed and validated using the most recent data. METHODS: The
      TR-DGU has been collecting data from severely injured patients since 1993. All
      injuries are coded according to the Abbreviated Injury Scale (AIS, version 2008).
      Severely injured patients from Europe (ISS >= 4) documented between 2010 and 2011
      were selected for developing the new score (n = 30,866), and 21,918 patients from
      2012 were used for validation. Age and injury codes were required, and
      transferred patients were excluded. Logistic regression analysis was applied with
      hospital mortality as the dependent variable. Results were evaluated in terms of
      discrimination (area under the receiver operating characteristic curve, AUC),
      precision (observed versus predicted mortality), and calibration (Hosmer-Lemeshow
      goodness-of-fit statistic). RESULTS: The mean age of the development population
      was 47.3 years; 71.6% were males, and the average ISS was 19.3 points. Hospital
      mortality rate was 11.5% in this group. The new RISC II model consists of the
      following predictors: worst and second-worst injury (AIS severity level), head
      injury, age, sex, pupil reactivity and size, pre-injury health status, blood
      pressure, acidosis (base deficit), coagulation, haemoglobin, and cardiopulmonary
      resuscitation. Missing values are included as a separate category for every
      variable. In the development and the validation dataset, the new RISC II
      outperformed the original RISC score, for example AUC in the development dataset
      0.953 versus 0.939. CONCLUSIONS: The updated RISC II prognostic score has several
      advantages over the previous RISC model. Discrimination, precision and
      calibration are improved, and patients with partial missing values could now be
      included. Results were confirmed in a validation dataset.

PMID- 25394598
TI  - [Not Available].

PMID- 25394600
TI  - Feedback informed treatment: evidence-based practice meets social construction.
AB  - This article explores the challenges presented by the mandate for evidence-based
      practice for family therapists who identify with the philosophical stance of
      social construction. The history of psychotherapy outcome research is reviewed,
      as are current findings that provide empirical evidence for an engaged, dialogic
      practice. The authors suggest that the binary between empiricism and social
      construction may be unhinged by understanding empiricism as a particular
      discursive frame (i.e., a particular way of talking, acting, and being in the
      world), one of many available as a way of understanding and talking about our
      work. Through a case vignette, the authors introduce the evidence-based practice
      of Feedback Informed Treatment as an elaboration of social construction, and as
      an example of bridging the gap between the discursive frames of empiricism and
      social construction. 

PMID- 25394601
TI  - The morphology and electrophysiology of the cochlea of the miniature pig.
AB  - To report the cochlear morphology and electrophysiology of Chinese experimental
      miniature pigs. Twenty Chinese experimental miniature pigs were used in this
      study. Auditory brainstem responses (ABR), cochlear endolymphatic potentials
      (EP), and the potassium concentrations of cochlear endolymph were recorded. Hair
      cell morphology was examined using electron microscopy. The capsule of cochlea of
      the miniature pig has three and one-half turns which contains a 39-mm long
      membranous labyrinth. The organ of Corti in the labyrinth encompasses three rows
      of outer hair cells and one row of inner hair cells. The stereocilia of the hair
      cells in the apical turn of the cochlea were significantly longer than those in
      the basal turn. The vestibular apparatus consists of three semicircular canals
      and the otolith organs. The average threshold of the ABR was 35-45 dB SPL (n=20)
      from 4 to 32 kHz. There was no significant difference in the threshold or latency
      of the ABR between 1-day-old and 30-day-old miniature pigs. The average EP value
      was 77.3+/-14 mV (n=9) and the average potassium concentration was 147.1+/-13 mM
      (n=5) recorded from the second turn of the cochlea. These studies on the cochlear
      morphology and electrophysiology of the miniature pigs help to establish the
      Chinese experimental miniature pig as an animal model for future studies in
      otology and audiology.

PMID- 25394602
TI  - Preventing mental health problems in offspring by targeting dietary intake of
      pregnant women.
AB  - BACKGROUND: The concept of 'early life programming' considers the importance of
      very early environmental exposures throughout the gestational period on the
      subsequent health outcomes of offspring. The role of maternal dietary intake,
      specifically, has been highlighted after recent studies have shown maternal diet
      quality to predict mental health problems in offspring. Even in the pre
      conception period, maternal nutrition can have permanent and sustained phenotypic
      consequences for offspring. DISCUSSION: Here, we consider these findings in the
      context of the primary prevention of mental disorders and argue that
      interventions that target maternal diet could be of significant value. SUMMARY:
      It is clear that, in order to reduce the burden of mental health issues across
      the lifespan, urgent action is required, particularly in the field of prevention.
      We thus call for the application and evaluation of targeted, primary prevention
      strategies that focus on dietary intake with the view to improve mental health
      outcomes of mothers and offspring during the postnatal period and beyond.

PMID- 25394603
TI  - Protection of mice against pandemic H1N1 influenza virus challenge after
      immunization with baculovirus-expressed stabilizing peptide fusion hemagglutinin
      protein.
AB  - Current influenza vaccines are produced in embryonated chicken eggs. However, egg
      based vaccines have various problems. To address these problems, recombinant
      protein vaccines have been developed as new vaccine candidates. Unfortunately,
      recombinant proteins frequently encounter aggregation and low stability during
      their biogenesis. It has been previously demonstrated that recombinantly
      expressed proteins can be greatly stabilized with high solubility by fusing
      stabilizing peptide (SP) derived from the C-terminal acidic tail of human
      synuclein (ATS). To investigate whether SP fusion proteins can induce protective
      immunity in mice, we produced influenza HA and SP fusion protein using a
      baculovirus expression system. In in vitro tests, SP-fused recombinant HA1 (SP
      rHA1) was shown to be more stable than recombinant HA1 (rHA1). Mice were
      immunized intramuscularly with baculovirus-expressed rHA1 protein or SP-rHA1
      protein (2 MUg/mouse) formulated with aluminum hydroxide. Antibody responses were
      determined by ELISA and hemagglutination inhibition assay. We observed that SP
      rHA1 immunization elicited HA-specific antibody responses that were comparable to
      rHA1 immunization. These results indicate that fusion of SP to rHA1 does not
      negatively affect the immunogenicity of the vaccine candidate. Therefore, it is
      possible to apply SP fusion technology to develop stable recombinant protein
      vaccines with high solubility. 

PMID- 25394604
TI  - Identification and Characterization of an Antifungal Protein, AfAFPR9, Produced
      by Marine-Derived Aspergillus fumigatus R9.
AB  - A fungal strain, R9, was isolated from the South Atlantic sediment sample and
      identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified
      from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified
      to be restrictocin, which is a member of the ribosome-inactivating proteins
      (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant
      pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum
      gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum
      inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 MUg/disc, respectively.
      Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion
      and denaturant tolerance. The iodoacetamide assay showed that the disulfide
      bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding
      for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed
      in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity
      against C. gloeosporioides, T. viride, and A. longipes. These results reveal the
      antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus
      fumigatus and indicated its potential application in controlling plant pathogenic
      fungi.

PMID- 25394605
TI  - A Putative Histone Deacetylase Modulates the Biosynthesis of Pestalotiollide B
      and Conidiation in Pestalotiopsis microspora.
AB  - Fungi of the genus Pestalotiopsis have drawn attention for their capability to
      produce an array of bioactive secondary metabolites that have potential for drug
      development. Here, we report the determination of a polyketide derivative
      compound, pestalotiollide B, in the culture of the saprophytic fungus
      Pestalotiopsis microspora NK17. Structural information acquired by analyses with
      a set of spectroscopic and chromatographic techniques suggests that
      pestalotiollide B has the same skeleton as the penicillide derivatives,
      dibenzodioxocinones, which are inhibitors of cholesterol ester transfer protein
      (CETP), and as purpactins A and C', inhibitors of acyl-CoA:cholesterol
      acyltransferase (ACAT). Strain NK17 can make a fairly high yield of
      pestalotiollide B (i.e., up to 7.22 mg/l) in a constitutive manner in liquid
      culture. Moreover, we found that a putative histone deacetylase gene, designated
      as hid1, played a role in the biosynthesis of pestalotiollide B. In the hid1 null
      mutant, the yield of pestalotiollide B increased approximately 2-fold to 15.90
      mg/l. In contrast, deletion of gene hid1 led to a dramatic decrease of conidia
      production of the fungus. These results suggest that hid1 is a modulator,
      concerting secondary metabolism and development such as conidiation in P.
      microspora. Our work may help with the investigation into the biosynthesis of
      pestalotiollide B and the development for new CETP and ACAT inhibitors.

PMID- 25394606
TI  - Complete Genome Sequence of Salmonella enterica Serovar Pullorum Multidrug
      Resistance Strain S06004 from China.
AB  - As Salmonella enterica serovar Pullorum remains a major economic problem for the
      poultry industries of countries with no efficient control measures, we presented
      a multidrug resistance strain S06004 (isolated from a clinically sick chicken in
      China in 2006) for genome sequencing. The genome comparison showed that the
      strain contained two prophages, the ST104 and prophage-4 (Fels2) of E. coli LF82,
      which were not detected in the only published genomes of S. Pullorum RKS5078 and
      CDC1983-67. In addition, the GyrA Ser83 point mutation, drugresistant genes, and
      many antibiotic pump systems that are present in S06004 may be contributing to
      the multidrug resistance of this strain.

PMID- 25394607
TI  - Accessory mental foramen: an anatomical study on dry mandibles and review of the
      literature.
AB  - PURPOSE: Since numerous surgical procedures in oral and maxillofacial surgery as
      well as several aspects of dental practice involve the mental region, the
      knowledge of its anatomical variations is essential for the clinician. Therefore,
      the aim of the present study was to evaluate the incidence and the anatomical
      features of the accessory mental foramen, which is occasionally traced
      additionally to the main mental foramen. MATERIAL AND METHODS: Ninety-six dry
      human mandibles of a Greek population and of unknown sex and age were examined in
      order to notice the presence of possible accessory mental foramina. The frequency
      of the accessory mental foramen was calculated, and its dimensions and its
      topographical relationship to the teeth of the mandible and the mental foramen
      were determined as well. RESULTS: A single accessory mental foramen was
      identified in 4.17% of the sample, while its mean transverse diameter was
      measured to be 1.09 mm and its mean distance from the mental foramen was 5.24 mm.
      CONCLUSIONS: The present study revealed an appreciable incidence of the accessory
      mental foramen in the Greek population, recognizably higher than the discovered
      incidence of past studies involving the Greek population. Consequently, the
      clinician should always be prepared to deal with an accessory mental foramen
      during surgical procedures.

PMID- 25394608
TI  - The lifestyle modification project: limiting pregnancy weight gain in obese
      women.
AB  - OBJECTIVE: To assess the impact of a group lifestyle intervention on gestational
      weight gain in a cohort of obese pregnant women. METHODS: A cohort study
      comparing 60 pregnant women enrolled in an educational intervention with controls
      from the same institution who receive routine prenatal care. Subjects were
      matched with controls by pre-pregnancy body mass index, parity and ethnicity.
      Subjects participated in group and individual counseling sessions focused on
      diet, exercise and weight goals. The primary outcome was gestational weight gain.
      RESULTS: A greater number of patients in the intervention group met the Institute
      of Medicine weight gain recommendations (35 versus 24, p = 0.0446). Mean
      gestational weight gain of participants was lower than the control group, but
      this was not statistically significant. Number of sessions attended was
      associated with a decrease in total weight gained. CONCLUSION: Educational
      interventions targeting obese pregnant women may be an effective way to limit
      gestational weight gain. Participation in educational sessions likely influences
      total weight gain.

PMID- 25394609
TI  - Evidence for association of the rs605059 polymorphism of HSD17B1 gene with
      recurrent spontaneous abortions.
AB  - OBJECTIVE: To investigate whether the missense rs605059 polymorphism of HSD17B1
      gene, which is expressed mainly in the placenta, is associated with recurrent
      spontaneous abortions (RSA). METHODS: This study group consisted of 138 women
      with three or more unexplained spontaneous abortions, before the 20th week of
      gestation, with the same partner, while 140 healthy women served as controls. To
      genotype the individuals, we used the polymerase chain reaction-restriction
      fragment length polymorphism method. RESULTS: The genotyping of the rs605059
      polymorphism revealed the frequencies 0.22, 0.45 and 0.33, for AA, GA and GG
      genotypes, respectively, for the patient group and 0.37, 0.41 and 0.22,
      respectively, for the control group. The A allele frequencies were 0.44 and 0.57
      for the patient and control group, respectively, and the G allele frequencies
      were 0.56 and 0.43 for the patient and control group, respectively. Statistical
      analysis of the results indicated the existence of significant differences in
      genotype and allele frequencies between the two groups. CONCLUSION: The rs605059
      polymorphism of the HSD17B1 gene is associated with increased risk of RSA in our
      Caucasian Greek population. Thus it could be used as a prognostic genetic marker
      for RSA.

PMID- 25394610
TI  - Association between maternal periodontitis and preterm and/or low birth weight
      infants in normal pregnancies.
AB  - OBJECTIVE: To relate the periodontal condition with the presence of periodontal
      bacteria in pregnant that had babies with preterm delivery or/and low weight at
      birth (PTLBW). METHODS: We recruited 134 pregnant women without systemic diseases
      attending at the Gynaecology and Obstetrics Room, from Maternal Provincial
      Hospital, Cordoba, Argentine. Pregnant were grouped according to the
      International Classification for a System of Periodontal Disease. A sample from
      periodontal pocket was extracted to identify Porphyromonas gingivalis (Pg),
      Treponema denticola (Td), Tannerella forsythia (Tf) Prevotella intermedia (Pi)
      and Agreggatibacter actinomycemcomitans (Aa). RESULTS: We identified 7 (5%) cases
      of children born underweight or preterm of mothers diagnosed with Gingivitis, 6
      (4%) in Mild Periodontitis and 4 (3%) in Moderate Periodontitis. We estimated
      that when Pi and/or Aa were not detected in the periodontal pockets of mothers,
      the infants had more than 129% chance of having normal birth weights (OR 3.47 for
      Pi and OR and 2.29 for Aa). The average age of the mothers who has PTLBW was 21
      +/- 3.5. The age showed an association with PTLBW (p < 0.0008). CONCLUSIONS: The
      presences of periodontal pathogens in periodontal pockets from pregnant with
      different periodontal status would associate with PTLBW infants when the mothers
      are young, and the normal term and normal birth weight infant are associated with
      the absence of periodonto bacteria like Pi and Aa.

PMID- 25394611
TI  - Does concurrent in utero exposure to buprenorphine and antidepressant medications
      influence the course of neonatal abstinence syndrome?
AB  - OBJECTIVE: To determine whether concurrent in utero exposure to buprenorphine and
      antidepressants impacts the course of neonatal abstinence syndrome (NAS) in
      infants. METHODS: A retrospective cohort study of 148 infants who were exposed to
      buprenorphine during pregnancy. Univariate and bivariate analyses were used to
      examine associations between concurrent maternal use of buprenorphine and
      antidepressants as compared to maternal use of buprenorphine alone. RESULTS: The
      time to onset of NAS resolution was significantly longer in infants exposed to
      both buprenorphine and antidepressants during pregnancy when compared to those
      exposed to buprenorphine alone (129.8 h versus 70.2 h, p = 0.042). CONCLUSIONS:
      Women who are prescribed both antidepressants and buprenorphine during pregnancy
      should be counseled about the possibility of a prolonged course of neonatal
      abstinence syndrome.

PMID- 25394612
TI  - Fetal bronchopulmonary malformations.
AB  - INTRODUCTION: Fetal body tumors are rare, but the ability to diagnose them has
      improved over recent years. Most masses discovered in the chest results from
      fetal bronchopulmonary malformations, such as congenital cystic adenomatoid
      malformation and bronchopulmonary sequestration. Congenital cystic adenomatoid
      malformation and bronchopulmonary sequestration have a reported incidence of 50%
      and 33% of all prenatally diagnosed lung lesions, respectively. MATERIAL AND
      METHODS: Retrospective analysis of the congenital cystic adenomatoid malformation
      and bronchopulmonary sequestration cases diagnosed or surveilled at our
      department, between January 2003 and March 2013. Prenatal examination, evolution,
      management and patient outcome were analyzed. RESULTS: A total of 918 fetal
      malformations were diagnosed at our hospital, 17 of them representing fetal
      bronchopulmonary malformations. The majority were diagnosed during the second
      trimester and stabilized or regressed during the third trimester of pregnancy.
      The pregnancies and deliveries had no other relevant findings or complications,
      except in three cases. Nine children required surgery. All of the children are
      healthy and have a normal development, with regular surveillance by the
      pediatricians. DISCUSSION: The majority of these fetal lung masses are isolated
      findings that partially regress during intrauterine life. With adequate postnatal
      surveillance and eventual surgery the prognosis is good.

PMID- 25394614
TI  - Does timing of initial surfactant treatment make a difference in rates of chronic
      lung disease or mortality in premature infants? An observational regional study.
AB  - OBJECTIVE: To compare two treatment strategies in preterm infants with or at risk
      of respiratory distress syndrome: early surfactant administration (within one
      hour of birth) versus late surfactant administration, in a geographically defined
      population. OUTCOME: The primary outcome was chronic lung disease (CLD) and
      mortality before/at 36 weeks. Secondary outcomes included: duration of mechanical
      ventilation and continuous positive airway pressure (CPAP), post-natal steroids
      for CLD and major neonatal morbidities. SUBJECTS: Premature infants born at 22-32
      weeks' gestation between January 2006 and December 2009. SETTING: Ten neonatal
      intensive care units (NICUs) in New South Wales (NSW) and Australian Capital
      Territory (ACT), Australia. DESIGN: Retrospective analysis of prospectively
      collected data from the regional NICU database in NSW and ACT. RESULTS: Of the
      2170 infants who received surfactant, 1182 (54.5%) and 988 (45.5%) received early
      and late surfactant, respectively. The early surfactant group was less mature
      (27.1 +/- 2.1 versus 29.4 +/- 2.1 weeks) and had more CLD and mortality (40.2%
      versus 20.0%). The multivariable analysis showed early surfactant to be
      associated with less duration of ventilation, longer duration of CPAP and longer
      hospital stay but had little or no impact on CLD/mortality. CONCLUSION: Early
      surfactant administration is associated with shorter duration of ventilation but
      does not appear to be significantly protective against CLD/mortality among
      premature infants. This may support the growing evidence for consideration of
      CPAP as an alternative to routine intubation and early surfactant administration.
      Further investigation from large randomized clinical trials is warranted to
      confirm these results.

PMID- 25394613
TI  - Fetal exposures and perinatal influences on the stool microbiota of premature
      infants.
AB  - OBJECTIVE: To test the hypothesis that maternal complications significantly
      affect gut colonization patterns in very low birth weight infants. METHODS: Forty
      nine serial stool samples were obtained weekly from nine extremely premature
      infants enrolled in a prospective longitudinal study. Sequencing of the bacterial
      16S rRNA gene from stool samples was performed to approximate the intestinal
      microbiome. Linear mixed effects models were used to evaluate relationships
      between perinatal complications and intestinal microbiome development. RESULTS:
      Subjects with prenatal exposure to a non-sterile intrauterine environment, i.e.
      prolonged preterm premature rupture of membranes (PPPROM) and chorioamnionitis
      exposure, were found to have a relatively higher abundance of potentially
      pathogenic bacteria in the stool across all time points compared to subjects
      without those exposures, irrespective of exposure to postnatal antibiotics.
      Compared with those delivered by Caesarean section, vaginally delivered subjects
      were found to have significantly lower diversity of stool microbiota across all
      time points, with lower abundance of many genera, most in the family
      Enterobacteriaceae. CONCLUSIONS: We identified persistently increased potential
      pathogen abundance in the developing stool microbiota of subjects exposed to a
      non-sterile uterine environment. Maternal complications appear to significantly
      influence the diversity and bacterial composition of the stool microbiota of
      premature infants, with findings persisting over time.

PMID- 25394615
TI  - Birth weight is associated with placental fat mass- and obesity-associated gene
      expression and promoter methylation in a Chinese population.
AB  - OBJECTIVE: To explore the relationship between birth weight and fat mass- and
      obesity-associated (FTO) gene expression and promoter methylation status in the
      Chinese population. METHODS: Seventy-five neonates and their mothers were
      recruited from Yuying Children's Hospital of Wenzhou Medical University. Subjects
      were divided into three groups by birth weight: low (< 3,500 g, n = 20), medium
      (3,500-3,999 g, n = 30) and high (>= 4,000 g, n = 25). Placental FTO transcript
      levels and promoter methylation were determined by quantitative PCR and Sequenom
      MassARRAY(r). RESULTS: Placental FTO mRNA expression was significantly increased
      in the high- and medium-weight groups compared to the low-weight group (p =
      0.023). Methylation rates of CpG11 sites were significantly decreased in high
      birth weight newborns (p = 0.018). Multiple linear regressions showed placental
      FTO mRNA, maternal pre-pregnancy body mass index (BMI) and CpG11 methylation rate
      were independently associated with increased fetal birth weight. Additionally,
      FTO mRNA expression was negatively associated with CpG6.7.8.9 methylation in
      mothers that underwent C-section. CONCLUSIONS: High placental FTO expression is
      associated with increased birth weight in Chinese neonates, and FTO promoter
      methylation level at a specific CpG site is negatively associated with birth
      weight. Further work is needed to determine the functionality of this CpG site in
      placentas.

PMID- 25394616
TI  - Association between renal function and cognitive ability domains in the Einstein
      aging study: a cross-sectional analysis.
AB  - BACKGROUND: The relationships between renal function and specific domains of
      cognitive function have rarely been explored in representative, community-based
      samples of older adults. We assessed the association between renal and cognitive
      function based on an extensive battery of neurocognitive tests. METHODS: In a
      sample of Einstein Aging Study participants (n = 649, age = 70+ years) we
      calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney
      Disease Epidemiology Collaboration formula. We predefined three groups based on
      eGFR units of mL/min/1.73 m(2) as low (<45), medium (45-59), and high (>=60).
      Thirteen neurocognitive tests were subjected to principle component analysis
      revealing three components: a global component, an episodic memory component, and
      a frontal-executive component. We first examined the relationship of eGFR group
      to cognitive performance in each domain and then examined subtests for the
      domains which proved to be statistically significant. RESULTS: The sample (mean =
      79.2, 61% = female) was distributed among eGFR categories as follows: low (n =
      67), medium (n = 151), and high (n = 431). The frontal-executive domain was
      significantly associated with poor cognitive performance in the low eGFR group (p
      <.001). When we examined the neuropsychological test components for frontal
      executive domain, performance was lower on two of four contributing tests (Trail
      Making Test Part B and the Digit Symbol Substitution test). Other domains of
      cognitive function were not associated with eGFR. CONCLUSIONS: Low eGFR is
      associated with reduced performance on executive function. Individuals with poor
      renal function should be assessed for cognitive impairment. Potential mechanisms
      are discussed.

PMID- 25394617
TI  - Association of Body Mass Index and Waist Circumference With Physical Functioning:
      The Vitality 90+ Study.
AB  - BACKGROUND: Both obesity and underweight are associated with impaired physical
      functioning, but related information on the oldest old population is scarce. Our
      purpose was to examine whether body mass index, waist circumference (WC), and
      their combination are associated with physical performance and activities of
      daily living (ADL) disability in 90-year-old women and men. METHODS: Data are
      from the Vitality 90+ Study, which is a population-based study of persons with
      age >=90 years living in the area of Tampere, Finland. Altogether 416 women and
      153 men, aged 90-91 years, provided data on body mass index, WC, chair stand, and
      Barthel Index. Comorbidity, physical exercise, smoking history, living residence,
      and sample year were used as covariates in multinomial logistic and logistic
      regression models. RESULTS: Women in the highest WC tertile had lower physical
      performance and were more likely unable to perform the chair stand than women in
      the lowest WC tertile. Women in the highest WC tertile were also more likely to
      have ADL disability, compared to the lowest WC tertile. In women, overweight and
      obesity were associated with ADL disability, but not when WC was included in the
      model. Men with body mass index >=25 kg/m(2) and WC < sex-specific median were
      less likely to have ADL disability. Similarly classified women were less likely
      to have low performance or unable to perform chair stand (marginally
      significant). CONCLUSIONS: High WC in the oldest old women, but not in men, is
      associated with both poor physical performance and ADL disability.

PMID- 25394618
TI  - Temporal trends of functional dependence and survival among older adults from
      1991 to 2010 in Sweden: toward a healthier aging.
AB  - BACKGROUND: Declines in functional dependence among older adults were observed
      before the 1990s, but there is uncertainty about subsequent trends. Our study
      aimed to verify the temporal trends in disability during 1991-2010 in an older
      Swedish population and to estimate the associated changes in survival. METHODS:
      Functional status in octogenarians and nonagenarians was assessed at seven
      occasions with intervals of 2-3 years. Sample size varied at each assessment with
      an average of 646 (range 212-1096). Disability was defined as difficulty in one
      or more of personal activities of daily living. We compared prevalence and
      incidence, as well as mortality, and survival associated with disability over the
      20-year period. RESULTS: Sex-standardized prevalence of disability remained
      steady over time with a tendency toward a gradual decline, and a statistically
      significant decrease was present among nonagenarians. Sex-standardized cumulative
      incidence also remained steady. The proportion of people with prevalent
      disability who died <3 years remained stable, as did the survival time of people
      with incident disability. In contrast, among nondisabled persons, 3-year
      mortality decreased significantly, and for octogenarians median survival time was
      1.3 years longer at the more recent assessment than a decade earlier.
      CONCLUSIONS: Both prevalence and incidence of disability remained stable over the
      last two decades in this urban Swedish population, with a trend toward a slow
      decline. Mortality remained steady among disabled persons but decreased among
      persons without disability, suggesting that increased life expectancy during the
      last two decades may be essentially driven by longer lives of functionally
      independent people.

PMID- 25394620
TI  - Dynamics of syndesmophyte growth in AS as measured by quantitative CT:
      heterogeneity within and among vertebral disc spaces.
AB  - OBJECTIVE: Syndesmophytes in AS typically grow slowly, but it is not known
      whether growth is uniform among syndesmophytes in the same intervertebral disc
      space (IDS) or among different IDSs in the same patient or if growth is
      heterogeneous. We examined the dynamics of syndesmophyte growth over 24 months
      using CT, with the main aim of determining if syndesmophytes in the same IDS or
      the same patient grow at similar rates. METHODS: We performed lumbar spine CT
      scans on 33 patients and measured syndesmophytes in four IDSs using a validated
      computer algorithm. Scans were done at baseline and 12 and 24 months. We compared
      absolute and percentage changes in volume from baseline to 12 months and to 24
      months among syndesmophytes in the same IDS and among four IDSs of each patient.
      We also examined whether growth among all IDSs differed between study years.
      RESULTS: Among 60 IDSs with at least two syndesmophytes at baseline (range 2-6),
      there was substantial heterogeneity in both absolute (P < 0.0001) and percentage
      (P = 0.0002) volume increases among syndesmophytes in the same IDS. Several IDSs
      had both syndesmophytes with no growth and syndesmophytes that increased by >100
      mm(3). Similarly there was significant heterogeneity in syndesmophyte growth
      among IDSs of individual patients. Increases in total syndesmophyte volume for
      each patient also tended to differ between study years (P = 0.07). CONCLUSION:
      Syndesmophytes in AS do not all grow continuously. Rates of growth over 24 months
      commonly differ between syndesmophytes in the same IDS and between different IDSs
      in the same patient, suggesting that local factors regulate syndesmophyte growth.

PMID- 25394619
TI  - Mitochondrial DNA Sequence Variation Associated With Peripheral Nerve Function in
      the Elderly.
AB  - BACKGROUND: Mitochondrial dysfunction is a prominent hallmark of many sensory
      neuropathies. The purpose of this study was to assess the influence of
      mitochondrial DNA sequence variation on peripheral nerve function in the
      population-based Health, Aging, and Body Composition Study. METHODS: We
      investigated the role of common mitochondrial DNA variation (n = 1,580) and
      complete mitochondrial DNA sequences (n = 138) on peroneal motor nerve conduction
      velocity and amplitude, average vibration detection threshold, and monofilament
      sensitivity. RESULTS: Nominal associations among common mitochondrial DNA
      variants and haplogroups were identified but were not statistically significant
      after adjustment for multiple comparisons. Sequence-based approaches were used to
      identify aggregate variant associations across the 16S rRNA (weighted-sum, p = 2E
      05 and variable threshold, p = 9E-06) for nerve conduction velocity. Several of
      these rare 16S variants occurred at or near sites with earlier disease
      associations and are also in close proximity to the peptidyl transferase center,
      which is the catalytic center of the 16S rRNA CONCLUSIONS: These results suggest
      that sequence variation related to mitochondrial protein synthesis/assembly is
      associated with peripheral nerve function and may provide insight into targets
      for intervention or new clinical strategies to preserve nerve function in late
      life.

PMID- 25394622
TI  - Cost effectiveness has its place, but so does common sense.

PMID- 25394621
TI  - Featured Article: Isolation, characterization, and cultivation of human
      hepatocytes and non-parenchymal liver cells.
AB  - Primary human hepatocytes (PHH) are considered to be the gold standard for in
      vitro testing of xenobiotic metabolism and hepatotoxicity. However, PHH
      cultivation in 2D mono-cultures leads to dedifferentiation and a loss of
      function. It is well known that hepatic non-parenchymal cells (NPC), such as
      Kupffer cells (KC), liver endothelial cells (LEC), and hepatic stellate cells
      (HSC), play a central role in the maintenance of PHH functions. The aims of the
      present study were to establish a protocol for the simultaneous isolation of
      human PHH and NPC from the same tissue specimen and to test their suitability for
      in vitro co-culture. Human PHH and NPC were isolated from tissue obtained by
      partial liver resection by a two-step EDTA/collagenase perfusion technique. The
      obtained cell fractions were purified by Percoll density gradient centrifugation.
      KC, LEC, and HSC contained in the NPC fraction were separated using specific
      adherence properties and magnetic activated cell sorting (MACS(r)). Identified
      NPC revealed a yield of 1.9 * 10(6) KC, 2.7 * 10(5) LEC and 4.7 * 10(5) HSC per
      gram liver tissue, showing viabilities >90%. Characterization of these NPC showed
      that all populations went through an activation process, which influenced the
      cell fate. The activation of KC strongly depended on the tissue quality and donor
      anamnesis. KC became activated in culture in association with a loss of viability
      within 4-5 days. LEC lost specific features during culture, while HSC went
      through a transformation process into myofibroblasts. The testing of different
      culture conditions for HSC demonstrated that they can attenuate, but not prevent
      dedifferentiation in vitro. In conclusion, the method described allows the
      isolation and separation of PHH and NPC in high quality and quantity from the
      same donor.

PMID- 25394623
TI  - Cell growth on pore-graded biomimetic TiO2 bone scaffolds.
AB  - In order to prevent soft tissue down-growth into osseous defect areas, membranes
      are used when placing bone graft materials. These membranes still show
      shortcomings in their performance and applications. In the current study, we
      choose an approach to integrate micro-porous surface structures into a macro
      porous scaffold. Low porous surfaces were fabricated by dip-coatings. Four
      different material compositions (titanium dioxide, polycaprolactone,
      polycaprolactone/water, polycaprolactone/beta-tricalcium phosphate) were
      characterised in terms of their appearance, architecture, topographical features
      and cell response. Titanium dioxide surfaces exhibited rougher and more complex
      textures, resulting in the highest number of osteosarcoma cells and distinct
      morphologies in terms of cell spreading. Polycaprolactone-based surfaces showed a
      smoother topography and enhanced microporosity, but the effect on secretion of
      the bone markers sclerostin and interleukin-6 from human osteoblasts was lower
      compared to secretion from cells cultured on titanium dioxide. beta-Tricalcium
      phosphate modification of polycaprolactone did not show any significant
      improvement regarding cell-material interaction. Nevertheless, surfaces show
      potential in the mechanical blockage of epithelial and soft tissue cells and may
      still permit sufficient nutrient transport. 

PMID- 25394624
TI  - The energetic benefits of tendon springs in running: is the reduction of muscle
      work important?
AB  - The distal muscle-tendon units of cursorial species are commonly composed of
      short muscle fibres and long, compliant tendons. It is assumed that the ability
      of these tendons to store and return mechanical energy over the course of a
      stride, thus avoiding the cyclic absorption and regeneration of mechanical energy
      by active muscle, offers some metabolic energy savings during running. However,
      this assumption has not been tested directly. We used muscle ergometry and
      myothermic measurements to determine the cost of force production in muscles
      acting isometrically, as they could if mechanical energy was stored and returned
      by tendon, and undergoing active stretch-shorten cycles, as they would if
      mechanical energy was absorbed and regenerated by muscle. We found no detectable
      difference in the cost of force production in isometric cycles compared with
      stretch-shorten cycles. This result suggests that replacing muscle stretch
      shorten work with tendon elastic energy storage and recovery does not reduce the
      cost of force production. This calls into question the assumption that reduction
      of muscle work drove the evolution of long distal tendons. We propose that the
      energetic benefits of tendons are derived primarily from their effect on muscle
      and limb architecture rather than their ability to reduce the cyclic work of
      muscle. 

PMID- 25394625
TI  - Total body water and water turnover rates in the estuarine diamondback terrapin
      (Malaclemys terrapin) during the transition from dormancy to activity.
AB  - Water and salt concentrations in an animal's body fluids can fluctuate with
      changing environmental conditions, posing osmoregulatory challenges that require
      behavioral and physiological adjustments. The purpose of this study was to
      investigate body water dynamics in the estuarine diamondback terrapin (Malaclemys
      terrapin), a species that undergoes seasonal dormancy in salt marsh habitats. We
      conducted a field study to determine the total body water (%TBW), water turnover
      rate (WTR) and daily water flux (DWF) of female terrapins in south eastern North
      Carolina pre- and post-emergence from winter dormancy. Terrapins were injected
      with [(2)H]deuterium on two occasions and washout of the isotope was monitored by
      taking successive blood samples during the period of transition from dormancy to
      activity. The WTR and DWF of dormant terrapins were significantly lower than
      those of active terrapins (WTR(dormant)=49.70+/-15.94 ml day(-1),
      WTR(active)=100.20+/-20.36 ml day(-1), DWF(dormant)=10.52+/-2.92%TBW day(-1),
      DWF(active)=21.84+/-7.30%TBW day(-1)). There was no significant difference in
      %TBW between dormant and active terrapins (75.05+/-6.19% and 74.54+/-4.36%,
      respectively). The results from this field study provide insight into the
      terrapin's ability to maintain osmotic homeostasis while experiencing shifts in
      behavioral and environmental conditions.

PMID- 25394626
TI  - Different transcription regulation routes are exerted by L- and D-amino acid
      enantiomers of peptide hormones.
AB  - Conversion of one or more amino acids in eukaryotic peptides to the D-enantiomer
      configuration is catalyzed by specific L/D-peptide isomerases and it is a poorly
      investigated post-translational modification. No common modified amino acid or
      specific modified position has been recognized, and mechanisms underlying changes
      in the peptide function provided by this conversion are not widely studied. The
      72 amino acid crustacean hyperglycemic hormone (CHH) in Astacidea crustaceans
      exhibits a co-existence of two peptide enantiomers with either D- or L
      phenylalanine as their third residue. It is a pleiotropic hormone regulating
      several physiological processes in different target tissues and along different
      time scales. CHH enantiomers differently affect time courses and intensities of
      examined processes. The short-term effects of the two isomers on gene expression
      were examined in the hepatopancreas, gills, hemocytes and muscles of the astacid
      Pontastacus leptodactylus. Gene expression in muscles and hemocytes was not
      affected by either of the isomers. Two modes of action for CHH were elucidated in
      the hepatopancreas and the gills: specific gene induction in both organs by D
      CHH, and targeted attenuation caused by both enantiomers in the gills.
      Consequently, a two-receptor system is proposed for conveying the effect of the
      two CHH isomers.

PMID- 25394627
TI  - Geographic variation in thermal physiological performance of the intertidal crab
      Petrolisthes violaceus along a latitudinal gradient.
AB  - Environmental temperature has profound effects on the biological performance and
      biogeographical distribution of ectothermic species. Variation of this abiotic
      factor across geographic gradients is expected to produce physiological
      differentiation and local adaptation of natural populations depending on their
      thermal tolerances and physiological sensitivities. Here, we studied geographic
      variation in whole-organism thermal physiology of seven populations of the
      porcelain crab Petrolisthes violaceus across a latitudinal gradient of 3000 km,
      characterized by a cline of thermal conditions. Our study found that populations
      of P. violaceus show no differences in the limits of their thermal performance
      curves and demonstrate a negative correlation of their optimal temperatures with
      latitude. Additionally, our findings show that high-latitude populations of P.
      violaceus exhibit broader thermal tolerances, which is consistent with the
      climatic variability hypothesis. Interestingly, under a future scenario of
      warming oceans, the thermal safety margins of P. violaceus indicate that lower
      latitude populations can physiologically tolerate the ocean-warming scenarios
      projected by the IPCC for the end of the twenty-first century. 

PMID- 25394629
TI  - Anaemia only causes a small reduction in the upper critical temperature of sea
      bass: is oxygen delivery the limiting factor for tolerance of acute warming in
      fishes?
AB  - To address how the capacity for oxygen transport influences tolerance of acute
      warming in fishes, we investigated whether a reduction in haematocrit, by means
      of intra-peritoneal injection of the haemolytic agent phenylhydrazine, lowered
      the upper critical temperature of sea bass. A reduction in haematocrit from 42+/
      2% to 20+/-3% (mean +/- s.e.m.) caused a significant but minor reduction in upper
      critical temperature, from 35.8+/-0.1 to 35.1+/-0.2 degrees C, with no
      correlation between individual values for haematocrit and upper thermal limit.
      Anaemia did not influence the rise in oxygen uptake between 25 and 33 degrees C,
      because the anaemic fish were able to compensate for reduced blood oxygen
      carrying capacity with a significant increase in cardiac output. Therefore, in
      sea bass the upper critical temperature, at which they lost equilibrium, was not
      determined by an inability of the cardio-respiratory system to meet the thermal
      acceleration of metabolic demands. 

PMID- 25394628
TI  - Air breathing in the Arctic: influence of temperature, hypoxia, activity and
      restricted air access on respiratory physiology of the Alaska blackfish Dallia
      pectoralis.
AB  - The Alaska blackfish (Dallia pectoralis) is an air-breathing fish native to
      Alaska and the Bering Sea islands, where it inhabits lakes that are ice-covered
      in the winter, but enters warm and hypoxic waters in the summer to forage and
      reproduce. To understand the respiratory physiology of this species under these
      conditions and the selective pressures that maintain the ability to breathe air,
      we acclimated fish to 5 degrees C and 15 degrees C and used respirometry to
      measure: standard oxygen uptake (M(O2)) in normoxia (19.8 kPa P(O2)) and hypoxia
      (2.5 kPa), with and without access to air; partitioning of standard M(O2) in
      normoxia and hypoxia; maximum M(O2) and partitioning after exercise; and critical
      oxygen tension (P(crit)). Additionally, the effects of temperature acclimation on
      haematocrit, haemoglobin oxygen affinity and gill morphology were assessed.
      Standard M(O2) was higher, but air breathing was not increased, at 15 degrees C
      or after exercise at both temperatures. Fish acclimated to 5 degrees C or 15
      degrees C increased air breathing to compensate and fully maintain standard M(O2)
      in hypoxia. Fish were able to maintain M(O2) through aquatic respiration when air
      was denied in normoxia, but when air was denied in hypoxia, standard M(O2) was
      reduced by ~30-50%. P(crit) was relatively high (5 kPa) and there were no
      differences in P(crit), gill morphology, haematocrit or haemoglobin oxygen
      affinity at the two temperatures. Therefore, Alaska blackfish depends on air
      breathing in hypoxia and additional mechanisms must thus be utilised to survive
      hypoxic submergence during the winter, such as hypoxia-induced enhancement in the
      capacities for carrying and binding blood oxygen, behavioural avoidance of
      hypoxia and suppression of metabolic rate.

PMID- 25394630
TI  - Antioxidant defence and stress protein induction following heat stress in the
      Mediterranean snail Xeropicta derbentina.
AB  - The Mediterranean snail Xeropicta derbentina (Pulmonata, Hygromiidae), being
      highly abundant in Southern France, has the need for efficient physiological
      adaptations to desiccation and over-heating posed by dry and hot environmental
      conditions. As a consequence of heat, oxidative stress manifests in these
      organisms, which, in turn, leads to the formation of reactive oxygen species
      (ROS). In this study, we focused on adaptations at the biochemical level by
      investigation of antioxidant defences and heat shock protein 70 (Hsp70)
      induction, both essential mechanisms of the heat stress response. We exposed
      snails to elevated temperature (25, 38, 40, 43 and 45 degrees C) in the
      laboratory and measured the activity of the antioxidant enzymes catalase (CAT)
      and glutathione peroxidase (GPx), determined the Hsp70 level and quantified lipid
      peroxidation. In general, we found a high constitutive level of CAT activity in
      all treatments, which may be interpreted as a permanent protection against ROS,
      i.e. hydrogen peroxide. CAT and GPx showed temperature-dependent activity: CAT
      activity was significantly increased in response to high temperatures (43 and 45
      degrees C), whereas GPx exhibited a significantly increased activity at 40
      degrees C, probably in response to high levels of lipid peroxides that occurred
      in the 38 degrees C treatment. Hsp70 showed a maximum induction at 40 degrees C,
      followed by a decrease at higher temperatures. Our results reveal that X.
      derbentina possesses a set of efficient mechanisms to cope with the damaging
      effects of heat. Furthermore, we demonstrated that, besides the well-documented
      Hsp70 stress response, antioxidant defence plays a crucial role in the snails'
      competence to survive extreme temperatures. 

PMID- 25394631
TI  - Buzzing during biosonar-based interception of prey in the delphinids Tursiops
      truncatus and Pseudorca crassidens.
AB  - Echolocating bats and toothed whales probe their environment with ultrasonic
      sound pulses, using returning echoes to navigate and find prey in a process that
      appears to have resulted from a remarkable convergence of the two taxa. Here, we
      report the first detailed quantification of echolocation behaviour during prey
      capture in the most studied delphinid species, a false killer whale and a
      bottlenose dolphin. Using acoustic DTAGs, we demonstrate that just prior to prey
      interception these delphinids change their acoustic gaze dramatically by reducing
      inter-click intervals and output >10-fold in a high repetition rate, low output
      buzz. Buzz click rates of 250-500 Hz for large but agile animals suggest that
      sampling rates during capture are scaled with the whale's manoeuvrability. These
      observations support the growing notion that fast sonar sampling accompanied by a
      low output level is critical for high rate feedback to inform motor patterns
      during prey interception in all echolocating toothed whales. 

PMID- 25394632
TI  - Bats coordinate sonar and flight behavior as they forage in open and cluttered
      environments.
AB  - Echolocating bats use active sensing as they emit sounds and listen to the
      returning echoes to probe their environment for navigation, obstacle avoidance
      and pursuit of prey. The sensing behavior of bats includes the planning of 3D
      spatial trajectory paths, which are guided by echo information. In this study, we
      examined the relationship between active sonar sampling and flight motor output
      as bats changed environments from open space to an artificial forest in a
      laboratory flight room. Using high-speed video and audio recordings, we
      reconstructed and analyzed 3D flight trajectories, sonar beam aim and acoustic
      sonar emission patterns as the bats captured prey. We found that big brown bats
      adjusted their sonar call structure, temporal patterning and flight speed in
      response to environmental change. The sonar beam aim of the bats predicted the
      flight turn rate in both the open room and the forest. However, the relationship
      between sonar beam aim and turn rate changed in the forest during the final stage
      of prey pursuit, during which the bat made shallower turns. We found flight
      stereotypy developed over multiple days in the forest, but did not find evidence
      for a reduction in active sonar sampling with experience. The temporal patterning
      of sonar sound groups was related to path planning around obstacles in the
      forest. Together, these results contribute to our understanding of how bats
      coordinate echolocation and flight behavior to represent and navigate their
      environment. 

PMID- 25394633
TI  - Metabolism and water loss rate of the haematophagous insect Rhodnius prolixus:
      effect of starvation and temperature.
AB  - Haematophagous insects suffer big changes in water needs under different levels
      of starvation. Rhodnius prolixus is the most important haematophagous vector of
      Chagas disease in the north of South America and a model organism in insect
      physiology. Although there have been some studies on patterns of gas exchange and
      metabolic rates, there is little information regarding water loss in R. prolixus.
      We investigated whether there is any modulation of water loss and metabolic rate
      under different requirements for saving water. We measured simultaneously CO2
      production, water emission and activity in individual insects in real time by
      open-flow respirometry at different temperatures (15, 25 and 35 degrees C) and
      post-feeding days (0, 5, 13 and 29). We found: (1) a clear drop in metabolic rate
      between 5 and 13 days after feeding that cannot be explained by activity and (2)
      a decrease in water loss rate with increasing starvation level, by a decrease in
      cuticular water loss during the first 5 days after feeding and a drop in the
      respiratory component thereafter. We calculated the surface area of the insects
      and estimated cuticular permeability. In addition, we analysed the pattern of gas
      exchange; the change from a cyclic to a continuous pattern was affected by
      temperature and activity, but it was not affected by the level of starvation.
      Modulation of metabolic and water loss rates with temperature and starvation
      could help R. prolixus to be more flexible in tolerating different periods of
      starvation, which is adaptive in a changing environment with the uncertainty of
      finding a suitable host. 

PMID- 25394634
TI  - Graded behavioral responses and habituation to sound in the common cuttlefish
      Sepia officinalis.
AB  - Sound is a widely available and vital cue in aquatic environments, yet most
      bioacoustic research has focused on marine vertebrates, leaving sound detection
      in invertebrates poorly understood. Cephalopods are an ecologically key taxon
      that likely use sound and may be impacted by increasing anthropogenic ocean
      noise, but little is known regarding their behavioral responses or adaptations to
      sound stimuli. These experiments identify the acoustic range and levels that
      elicit a wide range of secondary defense behaviors such as inking, jetting and
      rapid coloration change. Secondarily, it was found that cuttlefish habituate to
      certain sound stimuli. The present study examined the behavioral responses of 22
      cuttlefish (Sepia officinalis) to pure-tone pips ranging from 80 to 1000 Hz with
      sound pressure levels of 85-188 dB re. 1 MUPa rms and particle accelerations of 0
      17.1 m s(-2). Cuttlefish escape responses (inking, jetting) were observed between
      frequencies of 80 and 300 Hz and at sound levels above 140 dB re. 1 MUPa rms and
      0.01 m s(-2) (0.74 m s(-2) for inking responses). Body patterning changes and fin
      movements were observed at all frequencies and sound levels. Response intensity
      was dependent upon stimulus amplitude and frequency, suggesting that cuttlefish
      also possess loudness perception with a maximum sensitivity around 150 Hz.
      Cuttlefish habituated to repeated 200 Hz tone pips, at two sound intensities.
      Total response inhibition was not reached, however, and a basal response remained
      present in most animals. The graded responses provide a loudness sensitivity
      curve and suggest an ecological function for sound use in cephalopods. 

PMID- 25394635
TI  - Supervised accelerometry analysis can identify prey capture by penguins at sea.
AB  - Determining where, when and how much animals eat is fundamental to understanding
      their ecology. We developed a technique to identify a prey capture signature for
      little penguins from accelerometry, in order to quantify food intake remotely. We
      categorised behaviour of captive penguins from HD video and matched this to time
      series data from back-mounted accelerometers. We then trained a support vector
      machine (SVM) to classify the penguins' behaviour at 0.3 s intervals as either
      'prey handling' or 'swimming'. We applied this model to accelerometer data
      collected from foraging wild penguins to identify prey capture events. We
      compared prey capture and non-prey capture dives to test the model predictions
      against foraging theory. The SVM had an accuracy of 84.95+/-0.26% (mean +/- s.e.)
      and a false positive rate of 9.82+/-0.24% when tested on unseen captive data. For
      wild data, we defined three independent, consecutive prey handling observations
      as representing true prey capture, with a false positive rate of 0.09%. Dives
      with prey captures had longer duration and bottom times, were deeper, had faster
      ascent rates, and had more 'wiggles' and 'dashes' (proxies for prey encounter
      used in other studies). The mean (+/-s.e.) number of prey captures per foraging
      trip was 446.6+/-66.28. By recording the behaviour of captive animals on HD video
      and using a supervised machine learning approach, we show that accelerometry
      signatures can classify the behaviour of wild animals at unprecedentedly fine
      scales. 

PMID- 25394636
TI  - Burning down the house: IRF7 makes the difference for microglia.

PMID- 25394637
TI  - Radioiodine therapy in patients with type II amiodarone-induced thyrotoxicosis.
AB  - INTRODUCTION: The treatment of amiodarone-induced thyrotoxicosis (AIT) still
      remains a clinical challenge, requiring the cooperation of both endocrinologists
      and cardiologists. Unfortunately, even today AIT is related to significantly
      increased mortality. OBJECTIVES: The aim of this study was to compare the
      efficacy of radioidine therapy for type II AIT in 2 groups of patients: with high
      or normal radioiodine uptake and treated by amiodarone (AM) in the past (AM-
      group) and with low radioiodine uptake and currently treated with AM (AM+ group).
      PATIENTS AND METHODS: The AM- group included 57 patients and the AM+ group, 49.
      All patients received iodine-131 at a dose of 22mCi~800. Patient data were
      collected for over 2 years. RESULTS: After radioiodine administration, serum
      thyroid-stimulating hormone levels in the AM- group and AM+ group were 0.0 +/-0.0
      and 0.0 +/-0.0, respectively, at 1 month; 1.2 +/-3.3 and 0.6 +/-1.2,
      respectively, at 12 months; and 4.2 +/-3.6 and 1.9 +/-0.8, respectively, at 2
      years. All differences between the groups were statistically significant (P
      <0.0001). Free triiodothyronine and thyroxine levels were significantly higher in
      the AM+ group compared with the AM- group. During follow-up, death occurred in 22
      patients in the AM+ group and 6 patients in the AM- group. CONCLUSIONS:
      Radioiodine treatment is a safe and effective therapeutic modality for patients
      with type II AIT despite low radioiodine uptake, especially for patients with
      contraindications to other types of treatment (eg, thyroidectomy). Moreover,
      since thyrotoxicosis in patients with AIT is a significant risk factor for
      increased mortality, and since there are no alternative antiarrythmic treatments,
      radioiodine administration seems to be the only effective therapeutic modality.

PMID- 25394638
TI  - Absolute Theta Power in the Frontal Cortex During a Visuomotor Task: The Effect
      of Bromazepam on Attention.
AB  - Bromazepam is a benzodiazepine, which has been widely employed in the treatment
      of anxiety. We investigated the electrophysiological changes in absolute theta
      power within the frontal cortex when individuals performed a visuomotor task
      under bromazepam. The sample of 17 healthy individuals was randomized into 2
      experimental conditions, under which bromazepam 6 mg and placebo were
      administered on different days. All subjects were right -handed, with no mental
      or physical illness and were not using any psychoactive or psychotropic substance
      during the entire period of the study. We found an increase in reaction time
      under bromazepam compared with placebo . With regard to the electrophysiological
      variable, we found a lower theta power value in the prefrontal cortex prior to
      task execution, compared with after. We therefore suggested that this could be an
      increase of neural activity in this region, because of the subjects' readiness to
      perform the task, that is, because of their higher alertness. The right lateral
      frontal region showed lower theta power under bromazepam for pre- and post-finger
      movement. This could have occurred because of more effort to execute the task. In
      the left frontal region: premovement did not demonstrate any difference between
      conditions, possibly because the proposed task was simple to execute. In
      conclusion, theta power plays an important role in the analysis of visuomotor
      performance, assuming that bromazepam causes impairment on sustained attention
      and sensory perception. 

PMID- 25394639
TI  - Authors' reply to Rappuoli and colleagues, Black, and Glennie and colleagues.

PMID- 25394640
TI  - Neutrophil release of myeloperoxidase in systemic vasculature of obese women may
      put them at risk for preeclampsia.
AB  - Obesity is a risk factor for preeclampsia, but the reason for this risk is
      unknown. Neutrophils infiltrate into systemic blood vessels of both obese and
      preeclamptic women. Neutrophils are a major source of myeloperoxidase (MPO),
      which is associated with hypertension. We tested the hypothesis that systemic
      vasculature of both obese and preeclamptic women will have a significant presence
      of MPO as a result of neutrophil infiltration. We found that immunohistochemical
      staining of MPO was significantly greater in subcutaneous fat blood vessels of
      obese women than overweight women, which was significantly greater than normal
      weight women. Expression of MPO was significantly greater in maternal blood
      vessels of preeclamptic women than normal pregnant or normal nonpregnant women.
      In general, when vessels of overweight or normal pregnant women were stained it
      was primarily for leukocytes in the lumen and not infiltrated into the vessel. In
      contrast, in obese and preeclamptic women staining was present for leukocytes in
      the lumen, flattened, and adhered to the endothelium and infiltrated into the
      vessel wall. There was also extensive diffuse staining for MPO in vessels of
      obese and preeclamptic women. In conclusion, both obese and preeclamptic women
      have increased presence of MPO in systemic vasculature as a result of neutrophil
      infiltration. We speculate that obese women may be at risk of preeclampsia
      because their vasculature is already prone to hypertension. 

PMID- 25394641
TI  - Smoking and Preterm Birth.
AB  - Premature birth is a significant global problem and the leading cause of newborn
      deaths. Tobacco smoking has been associated with premature birth for over 50
      years. The mechanisms through which smoking exerts its effects on pregnancy
      outcomes remain unclear. In this review, we discuss rates of prematurity and
      smoking in pregnancy, the evidence of a causal relationship between tobacco and
      preterm birth, and proposed biochemical pathways through which the interaction is
      mediated. The suggested mechanisms include nicotine-induced vasoconstriction,
      carbon monoxide-induced fetal hypoxia, cadmium disruption of calcium signaling,
      altered steroid hormone production, disruption of prostaglandin synthesis, and
      changed responses to oxytocin. The relative importance of each of these pathways
      is yet to be ascertained. Further research is necessary to explore the mechanisms
      through which smoking exerts its effect on gestational length and the process of
      parturition. Moreover, the risks of nicotine replacement in pregnancy should be
      investigated further. 

PMID- 25394642
TI  - Exposing mouse oocytes to necrostatin 1 during in vitro maturation improves
      maturation, survival after vitrification, mitochondrial preservation, and
      developmental competence.
AB  - Necrostatin 1 (Nec1) is widely used in disease models to examine the contribution
      of receptor-interacting protein kinase 1 in cell death. The biological actions of
      Nec1 are blocking necrotic cell death. The purpose of this study was to
      investigate whether adding Nec1 into in vitro maturation (IVM) media, followed by
      vitrification procedures, could enhance the survival and developmental competency
      of oocytes. Germinal vesicle oocytes were matured in IVM medium containing 2
      different doses of Nec1 (0.5 and 1 MUmol/L). After IVM, the oocytes were
      vitrified using a 2-step exposure to equilibrium and vitrification solutions.
      After warming, the rates of survival, fertilization, embryonic development up to
      blastocyst in vitro, morphology of spindle and chromosome, membrane integrity,
      mitochondria integrity, and several gene expressions were evaluated. The survival
      and developmental competency of oocytes were higher in the 1 MUmol/L Nec1-treated
      group than control. The proportion with intact spindles/chromosomes and stable
      membranes was similar in all the groups. The mitochondrial integrity of all Nec1
      treated groups showed a higher score with strong staining. The 1 MUmol/L Nec1
      showed significantly increased expressions of Mad2, Gdf9, and Bcl2. The Cirp
      level had a tendency to be downregulated in the 0.5 umol/L Nec1 but upregulated
      in the 1 MUmol/L Nec1, compared with the control. The Mtgenome expressions were
      significantly decreased in both Nec1 groups. The supplementation of 1 MUmol/L
      Nec1 into the IVM medium could be beneficial for the survival and development of
      immature oocytes after vitrification. 

PMID- 25394643
TI  - Early Pregnancy Maternal Lipid Profiles and the Risk of Gestational Diabetes
      Mellitus Stratified for Body Mass Index.
AB  - OBJECTIVE: To determine associations between lipid profiles in early pregnancy
      stratified by body mass index (BMI) and risk of developing gestational diabetes
      mellitus (GDM). STUDY DESIGN: A total of 2488 healthy pregnant women were
      enrolled prospectively. Fasting plasma lipid profiles were measured at mean 11
      weeks of gestation including triglycerides (TGs), total cholesterol, high-density
      lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol (CHO). We
      assessed early pregnancy maternal lipid concentrations in different tertiles in
      association with the risk of GDM stratified for BMI. Multivariable logistic
      regression analyses were used to estimate the relative risk of GDM by calculating
      odds ratios and 95% confidence intervals (CIs). RESULTS: In univariate analyses,
      pregnant women with GDM had significantly increased serum TG, CHO, LDL
      concentrations, LDL/HDL ratio, and decreased LDL concentrations, compared to
      control groups, each P < .01, respectively. After adjustment for confounders,
      there was a 1.8-fold increase in risk for GDM in the lean group (95% CI: 1.2-2.7)
      and 2.7-fold increase in the obese group (95% CI: 1.1-6.6), respectively, if TG
      >= 1.58 mmol/L. About a 50% decrease in the risk of GDM was observed in lean
      women with HDL >= 2.22 mmol/L (95% CI: 0.3-0.9). No significant correlations of
      other lipid profiles with the risk of developing GDM were observed. CONCLUSION:
      Early pregnancy dyslipidemia is associated with the risk of developing GDM. Lean
      or obese women with higher TG concentrations are at an increased risk for
      developing GDM while lean women with high HDL are protected.

PMID- 25394644
TI  - Effectiveness and Safety of Lower Doses of Mifepristone Combined With Misoprostol
      for the Termination of Ultra-Early Pregnancy: A Dose-Ranging Randomized
      Controlled Trial.
AB  - This study aimed to investigate the effectiveness and safety of lower doses of
      mifepristone combined with misoprostol for the termination of ultra-early
      pregnancy. A total of 2500 women with ultra-early pregnancy (amenorrhea <= 35
      days) were randomly divided into 5 groups with gradually decreased dose of oral
      mifepristone from 150 to 50 mg followed by 200 ug of oral misoprostol 24 hours
      later. The primary end point was complete abortion without surgical intervention.
      Secondary end points were vaginal bleeding, return of menses, and side effects.
      Rates of complete abortion were high in all groups. Moreover, the lower doses of
      mifepristone led to shorter vaginal bleeding period, the return of menses on the
      expected date, and fewer side effects. Lower doses of mifepristone combined with
      200 ug of misoprostol are as effective and safe as higher doses of this
      combination for the termination of ultra-early pregnancy with lower possibility
      of vaginal bleeding and side effects. 

PMID- 25394645
TI  - Establishment of a New Ovarian Cancer Cell Line CA5171.
AB  - A new cell line, CA5171, derived from a chemotherapy-naive, high-grade
      undifferentiated ovarian carcinoma was established and characterized. The CA5171
      cells presented with cobblestone morphology and a doubling time of 24 hours. Gene
      mutation analysis showed that the cells belonged to the type II ovarian cancer
      pathway with mutations of PIK3CA, PTEN, and TP53. Single-nucleotide polymorphism
      array analysis showed no homozygous gene deletion; however, several loci of gene
      copy number gains were noted in chromosome 1, 2, 5, 9, 10, 12, 15, 16, 20, and X.
      The in vitro and in vivo experiments showed that the cells were sensitive to
      paclitaxel and doxorubicin, but resistant to cisplatin. The cells also presented
      epithelial-mesenchymal transition properties that may have been related to their
      invasion and migration potential. The CA5171 cells show the potential as a new
      cell line for studies on epithelial ovarian carcinoma. 

PMID- 25394646
TI  - Pelvic pain and quality of life of women with endometriosis during quadriphasic
      estradiol valerate/dienogest oral contraceptive: a patient-preference prospective
      24-week pilot study.
AB  - OBJECTIVE: The progestin dienogest (DNG) given alone effectively reduces pelvic
      pain of women with endometriosis. It is not clear whether the same occurs when
      DNG is associated with estradiol (E2). DESIGN: Patient preference prospective
      observational study. SETTING: Outpatient centre of university hospital. PATIENTS:
      40 patients with endometriosis and menstrual pain. INTERVENTIONS: 24-week
      treatment with a quadriphasic association of E2 valerate (E2V) and DNG or a
      nonsteroidal anti-inflammatory drug (NSAID) to be used only in case of pain
      (ketoprofene 200-mg tablets). MAIN OUTCOME MEASURES: Menstrual pain and, when
      present, intermenstrual pain, and dyspareunia were investigated by means of a 10
      cm visual analogue scale (VAS). Quality of life was investigated by the short
      form 36 (SF-36) of the health-related quality of life questionnaire. RESULTS:
      Final study group consists of 34 patients, 19 in the E2V/DNG group and 15 in the
      NSAID group. After 24 weeks, no significant modification of menstrual pain,
      intermenstrual pain, dyspareunia, or SF-36 score was observed in the NSAID group.
      Treatment with E2V/DNG reduced the VAS score of menstrual pain by 61% (P <
      .0001). In the subgroups of women with intermenstrual pain or dyspareunia,
      E2V/DNG reduced these complaints by 65% (P = .013) and 52% (P = .016),
      respectively. The reduction in menstrual (P = .0001) and intermenstrual pain (p =
      0.03) was significantly greater during E2V/DNG than NSAID. Quality of life
      improved during E2V/DNG (P = .0002), both in physical (P = .0003) and mental
      domains (P = .0065). Only a few minor adverse effects were described during
      E2V/DNG, and none caused withdrawal from treatment. CONCLUSION: In patients with
      endometriosis and pelvic pain, the 24-week administration of the quadriphasic
      association of E2V/DNG decreases pelvic pain and improves quality of life.

PMID- 25394647
TI  - Assessing metastasis risk after pre-operative anti-angiogenic therapy.
AB  - Anti-angiogenic drugs are approved for the treatment of several cancer types,
      generally in the inoperable locally advanced or metastatic setting and in
      combination with other anti-cancer agents. Recent clinical studies also suggest
      that anti-angiogenic drugs can be useful in the pre-operative (neoadjuvant)
      setting, by facilitating the shrinkage of the primary tumour and its surgical
      resection. However, the effects of neoadjuvant anti-angiogenic therapy on the
      ability of tumours to form distant metastases are unclear. In this issue of EMBO
      Molecular Medicine, Ebos et al (2014) present carefully performed pre-clinical
      studies in mice that analyse the effects of pre-operative anti-angiogenic therapy
      on tumour metastasis and survival.

PMID- 25394648
TI  - Resveratrol treatment of mice with pressure-overload-induced heart failure
      improves diastolic function and cardiac energy metabolism.
AB  - BACKGROUND: Although resveratrol has multiple beneficial cardiovascular effects,
      whether resveratrol can be used for the treatment and management of heart failure
      (HF) remains unclear. In the current study, we determined whether resveratrol
      treatment of mice with established HF could lessen the detrimental phenotype
      associated with pressure-overload-induced HF and identified physiological and
      molecular mechanisms contributing to this. METHODS AND RESULTS: C57Bl/6 mice were
      subjected to either sham or transverse aortic constriction surgery to induce HF.
      Three weeks post surgery, a cohort of mice with established HF (% ejection
      fraction <45) was administered resveratrol (~320 mg/kg per day). Despite a lack
      of improvement in ejection fraction, resveratrol treatment significantly
      increased median survival of mice with HF, lessened cardiac fibrosis, reduced
      gene expression of several disease markers for hypertrophy and extracellular
      matrix remodeling that were upregulated in HF, promoted beneficial remodeling,
      and improved diastolic function. Resveratrol treatment of mice with established
      HF also restored the levels of mitochondrial oxidative phosphorylation complexes,
      restored cardiac AMP-activated protein kinase activation, and improved myocardial
      insulin sensitivity to promote glucose metabolism and significantly improved
      myocardial energetic status. Finally, noncardiac symptoms of HF, such as
      peripheral insulin sensitivity, vascular function, and physical activity, were
      improved with resveratrol treatment. CONCLUSIONS: Resveratrol treatment of mice
      with established HF lessens the severity of the HF phenotype by lessening cardiac
      fibrosis, improving molecular and structural remodeling of the heart, and
      enhancing diastolic function, vascular function, and energy metabolism.

PMID- 25394649
TI  - Estimation of the contribution of short-lived radioiodines to the thyroid dose
      for the public in case of inhalation intake following the Fukushima accident.
AB  - The purpose of this paper is to present (1) the method of assessing the
      contribution of short-lived radioiodines to the thyroid for members of the public
      in Fukushima and neighbouring prefectures based on available data and (2) the
      results of a realistic assessment of such a contribution. The estimates of that
      contribution for the inhalation intake that occurred on the day of the main
      fallout (15 March 2011) are within 15 % of the dose to the thyroid from (131)I.
      The contribution to the thyroid dose from intake of (132)Te is higher than that
      from the intake of (133)I by a factor of ~3. The contribution of short-lived
      radioiodines to the thyroid dose for the public in the case of inhalation intake
      occurring as early as March 12 might be as great as 30-40 %. 

PMID- 25394650
TI  - Risk management policies and practices regarding radio frequency electromagnetic
      fields: results from a WHO survey.
AB  - This study aims to describe current risk management practices and policies across
      the world in relation to personal exposures from devices emitting radiofrequency
      fields, environmental exposures from fixed installations and exposures in the
      work environment. Data from 86 countries representing all WHO regions were
      collected through a survey. The majority of countries (76.8 %) had set exposure
      limits for mobile devices, almost all (90.7 %) had set public exposure limits for
      fixed installations and 76.5 % had specified exposure limits for personnel in
      occupational settings. A number of other policies had been implemented at the
      national level, ranging from information provisions on how to reduce personal
      exposures and restrictions of usage for certain populations, such as children or
      pregnant women to prevention of access around base stations. This study suggests
      that countries with higher mobile subscriptions tend to have set radiofrequency
      exposure limits for mobile devices and to have provisions on exposure
      measurements about fixed installations. 

PMID- 25394651
TI  - A composite model including visfatin, tissue polypeptide-specific antigen,
      hyaluronic acid, and hematological variables for the diagnosis of moderate-to
      severe fibrosis in nonalcoholic fatty liver disease: a preliminary study.
AB  - INTRODUCTION: Histopathological risk factors for end-stage liver failure in
      patients with nonalcoholic fatty liver disease (NAFLD) include nonalcoholic
      steatohepatitis (NASH) and advanced liver fibrosis. There is a need for
      noninvasive diagnostic methods for these 2 conditions. OBJECTIVES: The aim of
      this study was to investigate new laboratory variables with a predictive
      potential to detect advanced fibrosis (stages 2 and 3) in NAFLD. PATIENTS AND
      METHODS: The study involved 70 patients with histologically proven NAFLD of
      varied severity. Additional laboratory variables included zonulin, haptoglobin,
      visfatin, adiponectin, leptin, tissue polypeptide-specific antigen (TPSA),
      hyaluronic acid, and interleukin 6. RESULTS: Patients with NASH (NAFLD activity
      score of >=5) had significantly higher HOMA-IR values and serum levels of
      visfatin, haptoglobin, and zonulin as compared with those without NASH on
      histological examination. Advanced fibrosis was found in 16 patients (22.9%) and
      the risk factors associated with its prevalence were age, the ratio of
      erythrocyte count to red blood cell distribution width, platelet count, and serum
      levels of visfatin and TPSA. Based on these variables, we constructed a scoring
      system that differentiated between NAFLD patients with and without advanced
      fibrosis with a sensitivity of 75% and specificity of 100% (area under the
      receiver operating characteristic curve, 0.93). CONCLUSIONS: The scoring system
      based on the above variables allows to predict advanced fibrosis with high
      sensitivity and specificity. However, its clinical utility should be verified in
      further studies involving a larger number of patients.

PMID- 25394652
TI  - Body image in women with primary and secondary provoked vestibulodynia: a
      controlled study.
AB  - INTRODUCTION: Provoked vestibulodynia (PVD) is a women's genito-pelvic pain
      condition associated with psychosexual impairments, including depression. Body
      image (BI) has been found to be different in women with primary (PVD1) and
      secondary (PVD2) PVD. No controlled study has compared BI in women with PVD1 and
      PVD2 and investigated its associations with sexual satisfaction, sexual function,
      and pain. AIMS: The aims of this study were to (i) compare BI in women with PVD1,
      PVD2, and asymptomatic controls and (ii) to examine associations between BI and
      sexual satisfaction, sexual function, and pain during intercourse in women with
      PVD. METHODS: Fifty-seven women (20 with PVD1, 19 with PVD2, and 18 controls)
      completed measures of BI, sexual satisfaction, sexual function, pain during
      intercourse, and depression. MAIN OUTCOME MEASURES: The main outcome measures
      were (i) Global Measure of Sexual Satisfaction Scale, (ii) Female Sexual Function
      Index, and (iii) pain numerical rating scale. RESULTS: Controlling for
      depression, women with PVD1 reported more body exposure anxiety during sexual
      activities than women with PVD2 and controls F(2,51)=4.23, P=0.02. For women with
      PVD, more negative BI during sexual activities was associated with lower sexual
      satisfaction (beta=-0.45, P=0.02) and function (beta=-0.39, P=0.04) and higher
      pain during intercourse (beta=0.59, P=0.004). More positive body esteem was
      associated with higher sexual function (beta=0.34, P=0.05). CONCLUSIONS: Findings
      suggest that women with PVD1 present more body exposure anxiety during sexual
      activities than women with PVD2 and asymptomatic women. Body esteem and general
      attitudes toward women's genitalia were not significantly different between
      groups. Higher body exposure anxiety during sexual activities was associated with
      poorer sexual outcomes in women with PVD. Further studies assessing interventions
      targeting BI during sexual activities in this population are needed, as improving
      BI during sexual interactions may enhance sexual outcomes in women with PVD.

PMID- 25394653
TI  - Ambivalent journeys of hope: embryonic stem cell therapy in a clinic in India.
AB  - Stem cell therapy in non-Western countries such as India has received a lot of
      attention. Apart from media reports, there are a number of social science
      analyses of stem cell policy, therapy, and research, their ethical implications,
      and impact of advertising on patients. Nevertheless, in the media reports as well
      as in academic studies, experiences of patients, who undertake overseas journeys
      for stem cell therapy, have largely been either ignored or presented reductively,
      often as a "false hope." In this article, I analyze the experiences of patients
      and their "journeys of hope" to NuTech Mediworld, an embryonic stem cell therapy
      clinic in New Delhi, India. My analysis, which draws on my observations in the
      clinic and patients' experiences, instead of seeking to adjudicate whether
      embryonic stem cell therapy in clinics such as NuTech is right or wrong, true or
      false, focuses on how patients navigate and contest these concerns. I utilize
      Gilles Deleuze and Felix Guattari's "concepts," lines of flight and
      deterritorialization, to highlight how embryonic stem cell therapy's "political
      economy of hope" embodies deterritorialization of several "regimes of truth" and
      how these deterritorializations impact patients' experiences. 

PMID- 25394654
TI  - Contingencies of the will: Uses of harm reduction and the disease model of
      addiction among health care practitioners.
AB  - The concept of addiction as a disease is becoming firmly established in medical
      knowledge and practice at the same time as the logics of the harm reduction
      approach are gaining broader acceptance. How health care practitioners understand
      and intervene upon drug use among their patients is complicated by these two
      models. While harm reduction can be understood as a form of governmentality
      wherein drug-taking individuals express their regulated autonomy through self
      governance, the notion of addiction as a disease removes the option of self
      governance through negating the will of the individual. Through analysis of
      qualitative interviews conducted with 13 health care practitioners who provide
      care for economically marginalized people who use drugs in New York City, it was
      found that the absence of will articulated in constructions of addiction as
      disease offered a gateway through which health care practitioners could bring in
      ideological commitments associated with harm reduction, such as the de
      stigmatization of drug use. Despite differences in the attribution of agency,
      sewing together these two approaches allowed health care practitioners to work
      with drug-using patients in practical and compassionate ways. This resembles the
      strategic deployment of diverse subjectivities found in feminist, post-structural
      liberatory projects wherein differential subjectification proves tactical and
      productive. Although drug-using patients may enjoy the benefits of practical and
      compassionate health care, the conjoint facilitation and denouncement of their
      will occasioned by the use of both harm reduction and the disease model of
      addiction imply their management by both pastoral and disciplinary technologies
      of power. 

PMID- 25394655
TI  - Structural and functional correlates of behavioral pattern separation in the
      hippocampus and medial temporal lobe.
AB  - Structures of the medial temporal lobe (MTL) are known to be involved in
      declarative memory processes. However, little is known about how age-related
      changes in MTL structures, white matter integrity, and functional connectivity
      affect pattern separation processes in the MTL. In this study, we used magnetic
      resonance imaging (MRI) to measure the volumes of MTL regions of interest,
      including hippocampal subfields (dentate gyrus, CA3, CA1, and subiculum) in
      healthy older and younger adults. Additionally, we used diffusion tensor imaging
      to measure white matter integrity for both groups. Finally, we used functional
      MRI to acquire resting functional connectivity measures for both groups. We show
      that, along with age, the volume of left CA3/dentate gyrus predicts memory
      performance. Differences in fractional anisotropy and the strength of resting
      functional connections between the hippocampus and other cortical structures
      implicated in memory processing were not significant predictors of performance.
      As previous studies have only hinted, it seems that the size of left CA3/dentate
      gyrus contributes more to successful discrimination between similar mnemonic
      representations than other hippocampal sub-fields, MTL structures, and other
      neuroimaging correlates. Accordingly, the implications of aging and atrophy on
      lure discrimination capacities are discussed.

PMID- 25394656
TI  - Strong interplay between the electron spin lifetime in chemically synthesized
      graphene multilayers and surface-bound oxygen.
AB  - The electron spin lifetime in an assembly of chemically synthesized graphene
      sheets was found to be extremely sensitive to oxygen. Introducing small
      concentrations of physisorbed O2 onto the graphene surface reduced the
      exceptionally long 140 ns electron spin lifetime by an order of magnitude. This
      effect was completely reversible: Removing the O2 by using a dynamic vacuum
      restored the spin lifetime. The presence of covalently bound oxygen also
      decreased the electron spin lifetime in graphene, although to a far lesser extent
      compared to physisorbed O2 . The conduction electrons in graphene were found to
      play a significant role by counter-balancing the spin depolarization caused by
      oxygen molecules. Our results highlight the importance of chemical environment
      control and device packing in practical graphene-based spintronic applications. 

PMID- 25394657
TI  - Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial
      restitution, migration, and Rac1 activation.
AB  - Identification of pathways involved in wound healing is important for
      understanding the pathogenesis of various intestinal diseases. Cellular inhibitor
      of apoptosis protein 2 (cIAP2) regulates proliferation and migration in
      nonepithelial cells and is expressed in human colonocytes. The aim of the study
      was to investigate the role of cIAP2 for wound healing in the normal human colon.
      Wound tissue was generated by taking rectosigmoidal biopsies across an
      experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental
      ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells
      (IECs) was increased at the wound edge after 24 h (P < 0.05), returned to normal
      after reepithelialization, and correlated with the inflammatory reaction in the
      experimental wounds (P < 0.001). cIAP2 was induced in vitro in regenerating Caco2
      IECs after wound infliction (P < 0.01). Knockdown of cIAP2 caused a substantial
      impairment of the IEC regeneration through inhibition of migration (P < 0.005).
      cIAP2 overexpression lead to formation of migrating IECs and upregulation of
      expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming
      growth factor-beta1 enhanced the expression of cIAP2 but was not upregulated in
      wounds in vivo and in vitro. NF-kappaB and MAPK pathways did not affect cIAP2
      expression. cIAP2 is in conclusion a regulator of human intestinal wound healing
      through enhanced migration along with activation of Rac1, and the findings
      suggest that cIAP2 could be a future therapeutic target to improve intestinal
      wound healing. 

PMID- 25394658
TI  - Estradiol decreases taurine level by reducing cysteine sulfinic acid
      decarboxylase via the estrogen receptor-alpha in female mice liver.
AB  - Cysteine sulfinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO) are
      two rate-limiting enzymes in taurine de novo synthesis, and their expressions are
      associated with estrogen concentration. The present study was designed to
      determine the relationship between 17beta-estradiol (E2) and taurine in female
      mice liver. We initially observed the mice had lower levels of CSAD, CDO, and
      taurine during estrus than diestrus. We then, respectively, treated the
      ovariectomized mice, the cultured hepatocytes, and Hep G2 cells with different
      doses of E2, and the CSAD and CDO expressions and taurine levels were analyzed.
      The results showed that E2 decreased taurine level in the serum and the cultured
      cells by inhibiting CSAD and CDO expressions. Furthermore, we identified the
      molecular receptor types through which E2 plays its role in regulating taurine
      synthesis, and our results showed that estrogen receptor-alpha (ERalpha)
      expression was much higher than estrogen receptor-beta (ERbeta) in the liver and
      hepatocytes, and the inhibiting effects of E2 on CSAD, CDO, and taurine level
      were partially abrogated in the ICI-182,780-pretreated liver and hepatocytes, and
      in ERalpha knockout mice. These results indicate that estradiol decreases taurine
      content by reducing taurine biosynthetic enzyme expression in mice liver.

PMID- 25394659
TI  - Neurally mediated propagating discrete clustered contractions superimposed on
      myogenic ripples in ex vivo segments of human ileum.
AB  - Narrow muscle strips have been extensively used to study intestinal
      contractility. Larger specimens from laboratory animals have provided detailed
      understanding of mechanisms that underlie patterned intestinal motility. Despite
      progress in animal tissue, investigations of motor patterns in large, intact
      specimens of human gut ex vivo have been sparse. In this study, we tested whether
      neurally dependent motor patterns could be detected in isolated specimens of
      intact human ileum. Specimens (n = 14; 7-30 cm long) of terminal ileum were
      obtained with prior informed consent from patients undergoing colonic surgery for
      removal of carcinomas. Preparations were set up in an organ bath with an array of
      force transducers, a fiberoptic manometry catheter, and a video camera.
      Spontaneous and distension-evoked motor activity was recorded, and the effects of
      lidocaine, which inhibits neural activity, were studied. Myogenic contractions
      (ripples) occurred in all preparations (6.17 +/- 0.36/min). They were of low
      amplitude and formed complex patterns by colliding and propagating in both
      directions along the specimen at anterograde velocities of 4.1 +/- 0.3 mm/s and
      retrogradely at 4.9 +/- 0.6 mm/s. In five specimens, larger amplitude clusters of
      contractions were seen (discrete clustered contractions), which propagated
      aborally at 1.05 +/- 0.13 mm/s and orally at 1.07 +/- 0.09 mm/s. These consisted
      of two to eight phasic contractions that aligned with ripples. These motor
      patterns were abolished by addition of lidocaine (0.3 mM). The ripples continued
      unchanged in the presence of this neural blocking agent. These results
      demonstrate that both myogenic and neurogenic motor patterns can be studied in
      isolated specimens of human small intestine. 

PMID- 25394660
TI  - Deletion of intestinal epithelial insulin receptor attenuates high-fat diet
      induced elevations in cholesterol and stem, enteroendocrine, and Paneth cell
      mRNAs.
AB  - The insulin receptor (IR) regulates nutrient uptake and utilization in multiple
      organs, but its role in the intestinal epithelium is not defined. This study
      developed a mouse model with villin-Cre (VC) recombinase-mediated intestinal
      epithelial cell (IEC)-specific IR deletion (VC-IR(Delta/Delta)) and littermate
      controls with floxed, but intact, IR (IR(fl/fl)) to define in vivo roles of IEC
      IR in mice fed chow or high-fat diet (HFD). We hypothesized that loss of IEC-IR
      would alter intestinal growth, biomarkers of intestinal epithelial stem cells
      (IESC) or other lineages, body weight, adiposity, and glucose or lipid handling.
      In lean, chow-fed mice, IEC-IR deletion did not affect body or fat mass, plasma
      glucose, or IEC proliferation. In chow-fed VC-IR(Delta/Delta) mice, mRNA levels
      of the Paneth cell marker lysozyme (Lyz) were decreased, but markers of other
      differentiated lineages were unchanged. During HFD-induced obesity, IR(fl/fl) and
      VC-IR(Delta/Delta) mice exhibited similar increases in body and fat mass, plasma
      insulin, mRNAs encoding several lipid-handling proteins, a decrease in Paneth
      cell number, and impaired glucose tolerance. In IR(fl/fl) mice, HFD-induced
      obesity increased circulating cholesterol; numbers of chromogranin A (CHGA)
      positive enteroendocrine cells (EEC); and mRNAs encoding Chga, glucose-dependent
      insulinotrophic peptide (Gip), glucagon (Gcg), Lyz, IESC biomarkers, and the
      enterocyte cholesterol transporter Scarb1. All these effects were attenuated or
      lost in VC-IR(Delta/Delta) mice. These results demonstrate that IEC-IR is not
      required for normal growth of the intestinal epithelium in lean adult mice.
      However, our findings provide novel evidence that, during HFD-induced obesity,
      IEC-IR contributes to increases in EEC, plasma cholesterol, and increased
      expression of Scarb1 or IESC-, EEC-, and Paneth cell-derived mRNAs. 

PMID- 25394662
TI  - Increased gastrin gene expression provides a physiological advantage to mice
      under hypoxic conditions.
AB  - Hypoxia, or a low concentration of O2, is encountered in humans undertaking
      activities such as mountain climbing and scuba diving and is important
      pathophysiologically as a limiting factor in tumor growth. Although data on the
      interplay between hypoxia and gastrins are limited, gastrin expression is
      upregulated by hypoxia in gastrointestinal cancer cell lines, and gastrins
      counterbalance hypoxia by stimulating angiogenesis in vitro and in vivo. The aim
      of this study was to determine if higher concentrations of the gastrin precursor
      progastrin are protective against hypoxia in vivo. hGAS mice, which overexpress
      progastrin in the liver, and mice of the corresponding wild-type FVB/N strain
      were exposed to normoxia or hypoxia. Iron status was assessed by measurement of
      serum iron parameters, real-time PCR for mRNAs encoding critical iron regulatory
      proteins, and Perls' stain and atomic absorption spectrometry for tissue iron
      concentrations. FVB/N mice lost weight at a faster rate and had higher sickness
      scores than hGAS mice exposed to hypoxia. Serum iron levels were lower in hGAS
      than FVB/N mice and decreased further when the animals were exposed to hypoxia.
      The concentration of iron in the liver was strikingly lower in hGAS than FVB/N
      mice. We conclude that increased circulating concentrations of progastrin provide
      a physiological advantage against systemic hypoxia in mice, possibly by
      increasing the availability of iron stores. This is the first report of an
      association between progastrin overexpression, hypoxia, and iron homeostasis.

PMID- 25394661
TI  - SCFA transport in rat duodenum.
AB  - Bacterial or ingested food-derived short-chain fatty acids (SCFAs) are present in
      the duodenal lumen. Acetate, the most abundant SCFA in the foregut lumen, is
      absorbed immediately after ingestion, although the mechanism by which this
      absorption occurs is not fully understood. We investigated the distribution and
      function of candidate SCFA transporters in rat duodenum. The Na(+)-coupled
      monocarboxylate transporter-1 (SMCT1) was localized to the brush border, whereas
      the pH-dependent monocarboxylate transporter (MCT) 1 and MCT4 were localized to
      the duodenocyte basolateral membrane. In Ussing chambered duodenal mucosa,
      luminal acetate dose-dependently increased short-circuit current (Isc) in the
      presence of serosal bumetanide and indomethacin by a luminal Na(+)-dependent,
      ouabain-sensitive mechanism. The Isc response was inhibited dose-dependently by
      the SMCT1 nonsubstrate inhibitor ibuprofen, consistent with net electrogenic
      absorption of acetate via SMCT1. Other SCFAs and lactate also increased Isc.
      Furthermore, duodenal loop perfusion of acetate increased portal venous acetate
      concentration, inhibited by coperfusion of ibuprofen or a MCT inhibitor. Luminal
      acetate perfusion increased duodenal HCO3 (-) secretion via capsaicin-sensitive
      afferent nerve activation and cyclooxygenase activity, consistent with absorption
      mediated HCO3 (-) secretion. These results suggest that absorption of luminal
      SCFA via SMCT1 and MCTs increases duodenal HCO3 (-) secretion. In addition to
      SCFA sensing via free fatty acid receptors, the presence of rapid duodenal SCFA
      absorption may be important for the suppression of luminal bacterial colonization
      and implicated in the generation of functional dyspepsia due to bacterial
      overgrowth. 

PMID- 25394663
TI  - Enhancement of chondrocyte proliferation, distribution, and functions within
      polycaprolactone scaffolds by surface treatments.
AB  - Enhancement of porcine chondrocyte growth, distribution and functions within
      polycaprolactone (PCL) scaffolds was attempted using alkaline hydrolysis and
      oxygen plasma treatment. The hydrolysis of PCL was performed either before or
      after scaffold fabrication in the preparations of pre-hydrolyzed PCL (pre-HPCL)
      or post-HPCL scaffolds, respectively. The PCL, pre-HPCL, and post-HPCL scaffolds
      were subsequently plasma-treated to yield plasma-treated PCL, plasma-treated pre
      HPCL, and plasma-treated post-HPCL scaffolds, respectively. All scaffolds were
      comparatively characterized, in terms of surface morphology, hydrophilicity, and
      atomic composition using scanning electron microscopy, contact angle measurement
      and X-ray photoelectron spectroscopy, respectively. The interactions of
      chondrocytes with individual scaffolds were assessed, in terms of cartilage-gene
      expression and cartilaginous matrix production using reverse transcription
      polymerase chain reaction analysis and glycosaminoglycans (GAGs) assay,
      respectively. The cell infiltration and cartilaginous matrix distribution were
      investigated by histological and immunofluorescence analysis. The results
      revealed that the plasma treatment exhibited a more prominent effect on the
      enhancement of surface roughness and hydrophilicity of the scaffolds than the
      alkaline hydrolysis. The scaffolds subjected to both surface treatments
      stimulated the cells to secret more GAGs and type II collagen. The sequence of
      hydrolysis of PCL also evidently played a crucial role in the hydrophilicity of
      the materials and the cartilage-gene expression and cartilaginous matrix
      production of the cultured chondrocytes. The hydrolysis of PCL prior to the
      fabrication, followed by the oxygen plasma treatment of the resulting fabricated
      scaffold, yielded plasma-treated pre-HPCL scaffold with homogeneous hydrophilic
      characteristics all over the material. Consequently, the cells could proliferate
      well, infiltrate most deeply and ultimately produce the highest amounts of the
      cartilage-specific substances throughout this scaffold.

PMID- 25394664
TI  - A Matter of Low Self-Control? Exploring Differences Between Child Pornography
      Possessors and Child Pornography Producers/Distributers Using Self-Control
      Theory.
AB  - This study examined the demographic and background characteristic differences
      between those arrested for child pornography (CP) possession (only), or CP
      production/distribution, or an attempted or completed sexual exploitation of a
      minor (SEM) that involved the Internet in some capacity within the context of
      self-control theory using data from the second wave of the National Juvenile
      Online Victimization Study (N-JOV2). Results indicate few demographic
      similarities, which thereby suggest these are largely heterogeneous groupings of
      individuals. Results also indicate CP producers/distributers engaged in a greater
      number of behaviors indicative of low self-control compared with CP possessors.
      Specifically, offenders arrested for CP production/distribution were more likely
      to have (a) had problems with drugs/alcohol at the time of the crime and (b) been
      previously violent. In contrast, the only indicator of low self-control that
      reached statistical significance for CP possessors was the previous use of
      violence. Moreover, in contrast to CP producers/distributers, full-time
      employment and marital status may be important factors to consider in the
      likelihood of arrest for CP possessors, which is congruent with the tenets of
      self-control theory. 

PMID- 25394666
TI  - Should we use intensive hypoglycemic treatment in patients with advanced type 2
      diabetes?

PMID- 25394665
TI  - Schizophrenia genetics: building the foundations of the future.

PMID- 25394667
TI  - Investigating fruit and vegetable claims on Australian food packages.
AB  - OBJECTIVES: Fruit and vegetable claims on food packages are not regulated under
      Australian food standards. The present study aimed to: (i) investigate the number
      and healthiness of products carrying fruit and vegetable claims in Australia; and
      (ii) compare the nutrition composition of these products with fresh fruit and/or
      vegetables. DESIGN: Content analysis of fruit and vegetable claims on food
      packages. The Australian food standards nutrient profiling model was used to
      determine the proportion of products not meeting nutrient profiling criteria. The
      nutrient composition of products carrying claims referencing the servings of
      fruit and vegetables in the product were compared with that of the dominant fruit
      and/or vegetables in each product. SETTING: The five largest supermarket chains
      in Australia. SUBJECTS: All available products in the fruit snacks, soups and
      fruit and vegetable juices/fruit drinks categories (n 762) were surveyed.
      Nutrition composition, ingredients and claims were recorded for each product.
      RESULTS: Of the products surveyed, 48 % (n 366) carried at least one claim, of
      which 34 % (n 124) did not meet nutrient profiling. Products carrying claims
      referencing the number of servings of fruit and vegetables had more energy,
      sodium, saturated fat and sugar, and less fibre, than fresh fruit and/or
      vegetables (all P<0.001). CONCLUSIONS: Many products carried fruit and vegetable
      claims and were significantly higher in energy, saturated fat, sugars and sodium
      than fresh fruit and vegetables. Marketing these products as a way of meeting
      fruit and vegetable intake is inaccurate and potentially misleading. Fruit and
      vegetable claims should be regulated using nutrient profiling.

PMID- 25394668
TI  - Near-infrared fluorescent semiconducting polymer dots with high brightness and
      pronounced effect of positioning alkyl chains on the comonomers.
AB  - In recent years, semiconducting polymer dots (Pdots) have emerged as a novel
      class of extraordinarily bright fluorescent probes with burgeoning applications
      in bioimaging and sensing. While the desire for near-infrared (NIR)-emitting
      agents for in vivo biological applications increases drastically, the direct
      synthesis of semiconducting polymers that can form Pdots with ultrahigh
      fluorescence brightness is extremely lacking due to the severe aggregation-caused
      quenching of the NIR chromophores in Pdots. Here we describe the synthesis of
      dithienylbenzoselenadiazole (DBS)-based NIR-fluorescing Pdots with ultrahigh
      brightness and excellent photostability. More importantly, the fluorescence
      quantum yields of these Pdots could be effectively increased by the introduction
      of long alkyl chains into the thiophene rings of DBS to significantly inhibit the
      aggregation-caused emission quenching. Additionally, these new series of DBS
      based Pdots can be excited by a commonly used 488 nm laser and show a
      fluorescence quantum yield as high as 36% with a Stokes shift larger than 200 nm.
      Single-particle analysis indicates that the per-particle brightness of the Pdots
      is at least 2 times higher than that of the commercial quantum dot (Qdot705)
      under identical laser excitation and acquisition conditions. We also
      functionalized the Pdots with carboxylic acid groups and then linked biomolecules
      to Pdot surfaces to demonstrate their capability for specific cellular labeling
      without any noticeable nonspecific binding. Our results suggest that these DBS
      based NIR-fluorescing Pdots will be very practical in various biological imaging
      and analytical applications.

PMID- 25394669
TI  - Coinage metals binding as main group elements: structure and bonding of the
      carbene complexes [TM(cAAC)2] and [TM(cAAC)2](+) (TM = Cu, Ag, Au).
AB  - Quantum chemical calculations using density functional theory have been carried
      out for the cyclic (alkyl)(amino)carbene (cAAC) complexes of the group 11 atoms
      [TM(cAAC)2] (TM = Cu, Ag, Au) and their cations [TM(cAAC)2](+). The nature of the
      metal-ligand bonding was investigated with the charge and energy decomposition
      analysis EDA-NOCV. The calculations show that the TM-C bonds in the charged
      adducts [TM(cAAC)2](+) are significantly longer than in the neutral complexes
      [TM(cAAC)2], but the cations have much higher bond dissociation energies than the
      neutral molecules. The intrinsic interaction energies DeltaEint in [TM(cAAC)2](+)
      take place between TM(+) in the (1)S electronic ground state and (cAAC)2. In
      contrast, the metal-ligand interactions in [TM(cAAC)2] involve the TM atoms in
      the excited (1)P state yielding strong TM p(pi) -> (cAAC)2 pi backdonation, which
      is absent in the cations. The calculations suggest that the cAAC ligands in
      [TM(cAAC)2] are stronger pi acceptors than sigma donors. The trends of the
      intrinsic interaction energies and the bond dissociation energies of the metal
      ligand bonds in [TM(cAAC)2] and [TM(cAAC)2](+) give the order Au > Cu > Ag.
      Calculations at the nonrelativistic level give weaker TM-C bonds, particularly
      for the gold complexes. The trend for the bond strength in the neutral and
      charged adducts without relativistic effects becomes Cu > Ag > Au. The EDA-NOCV
      calculations suggest that the weaker bonds at the nonrelativistic level are
      mainly due to stronger Pauli repulsion and weaker orbital interactions. The NBO
      picture of the C-TM-C bonding situation does not correctly represent the nature
      of the metal-ligand interactions in [TM(cAAC)2]. 

PMID- 25394670
TI  - In response to Admission after sleep surgery is unnecessary in patients without
      cardiovascular disease.

PMID- 25394671
TI  - SOS1 and Ras regulate epithelial tight junction formation in the human airway
      through EMP1.
AB  - The human airway is lined with respiratory epithelial cells, which create a
      critical barrier through the formation of apical tight junctions. To investigate
      the molecular mechanisms underlying this process, an RNAi screen for guanine
      nucleotide exchange factors (GEFs) was performed in human bronchial epithelial
      cells (16HBE). We report that SOS1, acting through the Ras/MEK/ERK pathway, is
      essential for tight junction formation. Global microarray analysis identifies
      epithelial membrane protein 1 (EMP1), an integral tetraspan membrane protein, as
      a major transcriptional target. EMP1 is indispensable for tight junction
      formation and function in 16HBE cells and in a human airway basal progenitor-like
      cell line (BCi-NS1.1). Furthermore, EMP1 is significantly downregulated in human
      lung cancers. Together, these data identify important roles for SOS1/Ras and EMP1
      in tight junction assembly during airway morphogenesis. 

PMID- 25394672
TI  - Comparison of pulmonary involvement between patients expressing anti-PL-7 and
      anti-Jo-1 antibodies.
AB  - Anti-PL-7 is an anti-tRNA synthetase antibody, and interstitial lung disease
      (ILD) is the most frequent complication of anti-PL-7-associated antisynthetase
      syndrome. However, the features of ILD have not been fully elucidated. The
      present study retrospectively compares 7 and 15 patients who were positive for
      anti-PL-7 and anti-Jo-1 antibodies, respectively. The features of ILD did not
      significantly differ between the two groups, but the ratio of lymphocytes in
      bronchoalveolar lavage fluid was higher in the Jo-1 than in the PL-7 group. High
      resolution computed tomography revealed nonspecific interstitial pneumonia in all
      patients in the PL-7 group and organizing pneumonia in four of the 15 patients in
      the Jo-1 group. These findings suggest that pulmonary complications slightly
      differ between patients expressing anti-PL-7 and anti-Jo-1 antibodies. Further
      studies are required to clarify the features of ILD associated with PL-7.

PMID- 25394673
TI  - Diagnostic value of pleural fluid obtained from a chest tube collection system.
AB  - BACKGROUND: Pleural fluid is typically drawn directly from the pleural space for
      diagnostic studies, but occasionally analyses are desired when a chest tube is
      already in place and a traditional approach is not feasible. The diagnostic value
      of analyzing fluid samples obtained from the pleural fluid collection system
      after chest tube insertion is unknown. METHODS: We performed a prospective
      observational study of patients in whom chest tube placement was planned for
      clinical indications. Diagnostic studies were performed on fluid obtained from
      the pleural space at the time of tube insertion and then repeated 2, 6, and 24 h
      later on samples obtained from the fluid collection system. RESULTS: Fifty-five
      percent of the 23 effusions studied met light's criteria for exudate at baseline.
      Lactate dehydrogenase (LDH) varied considerably over time from baseline measures
      with only 25 % of measures at 24 h falling within 25 % of baseline levels. The
      sensitivity for exudate by LDH remained 100 % with poor specificity ranging 50-69
      % with repeat measures. Total protein exhibited less variability with 85 % of
      measures at 24 h falling within 25 % of baseline measure. Sensitivity and
      specificity at 24 h were 88 and 82 %, respectively. Repeat measures of
      cholesterol, albumin, and triglycerides generally correlated well (Spearman's rho
      > 0.90) with baseline values. Measures of glucose and cell counts varied
      considerably from baseline. CONCLUSIONS: Analysis of pleural fluid from a chest
      tube collection system is feasible and can provide useful diagnostic information.
      Practitioners should consider the test characteristics of each measure when
      interpreting samples obtained.

PMID- 25394674
TI  - Good coercion: patients' moral evaluation of coercion in mental health care.
AB  - The use of coercion in mental health care is not self-evident and requires moral
      justification. A joint understanding is difficult to achieve, because patients
      and health professionals often evaluate coercion differently. The present study
      aims to discuss patients' 'moral' evaluation of coercion. We believe that such a
      focus can form the basis for a better and more differentiated understanding of
      how we evaluate coercion. This is a qualitative study based on participant
      observation and interviews with patients. In order to focus specifically on the
      moral evaluation of coercion, we looked within patients' narratives to examine
      whether we could differentiate between how they experienced coercion and how they
      morally evaluated its use, and how they envision/describe good coercion. We found
      that patients differentiated implicitly between experiences and moral evaluation.
      The findings have been ordered into three types of reactions: agreeing and
      accepting, fighting or resisting, and resignation. Further reflection upon
      patients' positive and negative moral evaluations of coercion resulted in the
      formulation of different concrete elements at three levels: threshold elements,
      process elements, and empathic elements. These elements helped us to understand
      what these patients considered 'good coercion'. The implications are that good
      clinical practice cannot be separated from the formal, moral evaluation of
      coercion. A differentiated moral understanding of coercion can form the basis for
      better and more sensitive communication about coercion among all those involved.
      A more respectful dialogue on the moral evaluation of coercion might also raise
      awareness during both the decision-making process and the actual practising of
      coercion. 

PMID- 25394675
TI  - Sperm competition generates evolution of increased paternal investment in a sex
      role-reversed seed beetle.
AB  - When males provide females with resources at mating, they can become the limiting
      sex in reproduction, in extreme cases leading to the reversal of typical
      courtship roles. The evolution of male provisioning is thought to be driven by
      male reproductive competition and selection for female fecundity enhancement. We
      used experimental evolution under male- or female-biased sex ratios and limited
      or unlimited food regimes to investigate the relative roles of these routes to
      male provisioning in a sex role-reversed beetle, Megabruchidius tonkineus, where
      males provide females with nutritious ejaculates. Males evolving under male
      biased sex ratios transferred larger ejaculates than did males from female-biased
      populations, demonstrating a sizeable role for reproductive competition in the
      evolution of male provisioning. Although larger ejaculates elevated female
      lifetime offspring production, we found little evidence of selection for larger
      ejaculates via fecundity enhancement: males evolving under resource-limited and
      unlimited conditions did not differ in mean ejaculate size. Resource limitation
      did, however, affect the evolution of conditional ejaculate allocation. Our
      results suggest that the resource provisioning that underpins sex role reversal
      in this system is the result of male-male reproductive competition rather than of
      direct selection for males to enhance female fecundity.

PMID- 25394676
TI  - Anti-inflammatory activity of SMP30 modulates NF-kappaB through protein tyrosine
      kinase/phosphatase balance.
AB  - Recent studies on senescence marker protein-30 (SMP30) have shown that it has an
      important functional role in the aging process, but its precise participation in
      cellular works has not been fully determined. We hypothesize that SMP30 plays
      crucial roles in signaling processes by modulating the balance of protein
      tyrosine kinase (PTK)/protein tyrosine phosphatase (PTP) and in activating
      proinflammatory NF-kappaB. An experimental paradigm of gain and loss of SMP30
      function was established using SMP30-overexpressed YPEN-1 cells (herein referred
      to as "SMP30(+) cells") and SMP30 (Y/-) knockout mouse kidneys. The resulting
      data show that SMP30 expression suppressed oxidative stress-induced PTK/PTP
      dysregulation and PP1/2A inactivation in SMP30(+) cells, leading to the
      suppression of NF-kappaB activation. In the kidneys of SMP30 (Y/-) mice, SMP30
      deficiency was found to induce NF-kappaB activation via the upstream signaling of
      NIK/IKK and MAPKs and to upregulate downstream NF-kappaB-responsive gene
      expression. In this study, we also demonstrate for the first time that SMP30
      deficiency induced PTK activity in SMP30 (Y/-) kidneys, thereby significantly
      increasing the tyrosine phosphorylation of a catalytic subunit of PP2A (PP2Ac
      Tyr307). Based on these findings, we propose that SMP30 involves NF-kappaB
      regulation through the PTK/PTP balance and that the age-related decrease of SMP30
      causes NF-kappaB activation, which contributes to an exacerbation of the
      inflammatory process during aging. KEY MESSAGES: SMP30-deficient mice induced a
      shorter lifespan and redox changes. Overexpression of SMP30 prevented oxidative
      stress insults. The depletion of SMP30 increased redox-related PTK/PTP imbalance
      and PP1/PP2A inactivation. The depletion of SMP30 caused an elevation of NF
      kappaB-responsive inflammatory markers. SMP30 may be a potent inhibitory protein
      against oxidative stress and chronic inflammation.

PMID- 25394677
TI  - Resveratrol prevents pathological but not physiological cardiac hypertrophy.
AB  - The mechanisms responsible for how resveratrol inhibits pathological left
      ventricular hypertrophy (LVH) but not physiological LVH have not been elucidated.
      Herein, we show that in rat cardiomyocytes, lower concentrations of resveratrol
      (0.1 and 1 MUM) are efficient at selectively inhibiting important regulators
      involved in pathological LVH (such as nuclear factor of activated T cells (NFAT))
      while not affecting pathways involved in physiological LVH (Akt and p70S6 kinase
      (p70S6K)). These differential responses are also observed in both mouse and rat
      models of in vivo physiological and pathological LVH. Interestingly, in all of
      the experiments involving a low concentration of resveratrol (1 MUM), the
      observed effects on Akt, p70S6K, and NFAT were independent from AMP-activated
      protein kinase (AMPK) activation while these effects at higher concentrations of
      resveratrol (50 MUM) were potentiated by AMPK activation. In summary, we show
      that resveratrol can concentration/dose selectively inhibit various pro
      hypertrophic signaling pathways and that resveratrol has differential effects on
      the modification of these signaling cascades in response to pathological stimuli
      versus physiological stimuli. This has important clinical implications as our
      findings support the concept that resveratrol may be useful in the selective
      treatment of pathological LVH. KEY MESSAGE: Resveratrol differentially regulates
      pathological and physiological cardiac hypertrophy. Resveratrol dose selectively
      inhibits pathological cardiac signaling pathways. Resveratrol inhibits NFAT
      dependent transcription. At low concentrations, effects of resveratrol are AMPK
      independent. Resveratrol may be used to selectively treat pathological cardiac
      hypertrophy.

PMID- 25394678
TI  - Gene therapy for haemophilia.
AB  - BACKGROUND: Haemophilia is a genetic disorder which is characterized by
      spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and
      other soft tissues. Current methods of treatment are expensive, challenging and
      involve regular administration of clotting factors. Gene therapy has recently
      been prompted as a curative treatment modality. OBJECTIVES: To evaluate the
      safety and efficacy of gene therapy for treating people with haemophilia A or B.
      SEARCH METHODS: We searched the Cochrane Cystic Fibrosis & Genetic Disorders
      Group's Coagulopathies Trials Register, compiled from electronic database
      searches and handsearching of journals and conference abstract books. We also
      searched the reference lists of relevant articles and reviews.Date of last
      search: 06 November 2014. SELECTION CRITERIA: Eligible trials included randomised
      or quasi-randomised clinical trials, including controlled clinical trials
      comparing gene therapy (with or without standard treatment) with standard
      treatment (factor replacement) or other 'curative' treatment such as stem cell
      transplantation individuals with haemophilia A or B of all ages who do not have
      inhibitors to factor VIII or IX. DATA COLLECTION AND ANALYSIS: No trials of gene
      therapy for haemophilia were found. MAIN RESULTS: No trials of gene therapy for
      haemophilia were identified. AUTHORS' CONCLUSIONS: No randomised or quasi
      randomised clinical trials of gene therapy for haemophilia were identified. Thus,
      we are unable to determine the effects of gene therapy for haemophilia. Gene
      therapy for haemophilia is still in its nascent stages and there is a need for
      well-designed clinical trials to assess the long-term feasibility, success and
      risks of gene therapy for people with haemophilia.

PMID- 25394680
TI  - Puffy skin disease (PSD) in rainbow trout, Oncorhynchus mykiss (Walbaum): a case
      definition.
AB  - Puffy skin disease (PSD) is a disease that causes skin pathology in rainbow
      trout, Oncorhynchus mykiss (Walbaum). Incidence of PSD in UK fish farms and
      fisheries has increased sharply in the last decade, with growing concern from
      both industry sectors. This paper provides the first comprehensive case
      definition of PSD, combining clinical and pathological observations of diseased
      rainbow trout from both fish farms and fisheries. The defining features of PSD,
      as summarized in the case definition, were focal lateral flank skin lesions that
      appeared as cutaneous swelling with pigment loss and petechiae. These were
      associated with lethargy, poor body condition, inappetance and low level
      mortality. Epidermal hyperplasia and spongiosis, oedema of the dermis stratum
      spongiosum and a mild diffuse inflammatory cellularity were typical in
      histopathology of skin. A specific pathogen or aetiology was not identified.
      Prevalence and severity of skin lesions was greatest during late summer and
      autumn, with the highest prevalence being 95%. Atypical lesions seen in winter
      and spring were suggestive of clinical resolution. PSD holds important
      implications for both trout aquaculture and still water trout fisheries. This
      case definition will aid future diagnosis, help avoid confusion with other skin
      conditions and promote prompt and consistent reporting. 

PMID- 25394679
TI  - Sepsis-associated hyperlactatemia.
AB  - There is overwhelming evidence that sepsis and septic shock are associated with
      hyperlactatemia (sepsis-associated hyperlactatemia (SAHL)). SAHL is a strong
      independent predictor of mortality and its presence and progression are widely
      appreciated by clinicians to define a very high-risk population. Until recently,
      the dominant paradigm has been that SAHL is a marker of tissue hypoxia.
      Accordingly, SAHL has been interpreted to indicate the presence of an 'oxygen
      debt' or 'hypoperfusion', which leads to increased lactate generation via
      anaerobic glycolysis. In light of such interpretation of the meaning of SAHL,
      maneuvers to increase oxygen delivery have been proposed as its treatment.
      Moreover, lactate levels have been proposed as a method to evaluate the adequacy
      of resuscitation and the nature of the response to the initial treatment for
      sepsis. However, a large body of evidence has accumulated that strongly
      challenges such notions. Much evidence now supports the view that SAHL is not due
      only to tissue hypoxia or anaerobic glycolysis. Experimental and human studies
      all consistently support the view that SAHL is more logically explained by
      increased aerobic glycolysis secondary to activation of the stress response
      (adrenergic stimulation). More importantly, new evidence suggests that SAHL may
      actually serve to facilitate bioenergetic efficiency through an increase in
      lactate oxidation. In this sense, the characteristics of lactate production best
      fit the notion of an adaptive survival response that grows in intensity as
      disease severity increases. Clinicians need to be aware of these developments in
      our understanding of SAHL in order to approach patient management according to
      biological principles and to interpret lactate concentrations during sepsis
      resuscitation according to current best knowledge. 

PMID- 25394681
TI  - Effects of branched-chain amino acids and zinc-enriched nutrients on
      prognosticators in HCV-infected patients: a multicenter randomized controlled
      trial.
AB  - Branched-chain amino acids (BCAAs) and trace element deficiencies are associated
      with poor prognosis in hepatitis C virus (HCV)-infected patients. The aim of this
      study was to investigate the effects of BCAA and zinc-enriched supplementation on
      prognostic factors in HCV-infected patients. Fifty-three HCV-infected patients
      were enrolled in this multicenter randomized controlled trial. The patients were
      assigned to either the placebo (n=27) or supplement group (n=26; 6,400 mg/day
      BCAAs and 10 mg/day zinc) and were followed up for 60 days. Primary outcomes were
      prognostic factors for chronic liver disease, including the serum BCAA-to
      tyrosine ratio (BTR), zinc levels and alpha-fetoprotein (AFP) levels. There were
      no significant differences in any of the prognostic factors between the placebo
      and supplement groups at baseline. In the supplement group, the BTR and zinc
      levels were significantly increased compared with the placebo group (BTR: 5.14 +/
      1.59 vs. 4.23 +/- 1.14, P=0.0290; zinc: 76 +/- 11 vs. 68 +/- 11 ug/dl,
      P=0.0497). No significant differences were observed in AFP levels between the
      groups in the whole analysis. However, a stratification analysis showed a
      significant reduction in DeltaAFP levels in the supplement group, with elevated
      AFP levels compared with the other groups (-2.72 +/- 3.45 ng/ml, P=0.0079). It
      was demonstrated that BCAA and zinc-enriched supplementation increased the BTR
      and zinc levels in the HCV-infected patients. Furthermore, the supplementation
      reduced the serum AFP levels in patients who had elevated serum AFP levels at
      baseline. Thus, BCAA and zinc-enriched supplementation may prolong the survival
      of HCV-infected patients by improving amino acid imbalance and zinc deficiency,
      and by partly downregulating AFP.

PMID- 25394683
TI  - Threading chalcogenide layers with polymer chains.
AB  - Inserting polymers into a crystalline inorganic matrix to understand the
      structure, position, and the structure-property relationships of the resulting
      composites is important for designing new inorganic-organic materials and tuning
      their properties. Single crystals of polymer-chalcogenide composites were
      successfully prepared by trapping polyethyleneglycol within a selenidostannate
      matrix under surfactant-thermal conditions. This work might provide a new
      strategy for preparing novel crystalline polymer-inorganic composites through
      encapsulating polymer chains within inorganic matrices. 

PMID- 25394682
TI  - Analog modulation of spike-evoked transmission in CA3 circuits is determined by
      axonal Kv1.1 channels in a time-dependent manner.
AB  - Synaptic transmission usually depends on action potentials (APs) in an all-or
      none (digital) fashion. Recent studies indicate, however, that subthreshold
      presynaptic depolarization may facilitate spike-evoked transmission, thus
      creating an analog modulation of spike-evoked synaptic transmission, also called
      analog-digital (AD) synaptic facilitation. Yet, the underlying mechanisms behind
      this facilitation remain unclear. We show here that AD facilitation at rat CA3
      CA3 synapses is time-dependent and requires long presynaptic depolarization (5-10
      s) for its induction. This depolarization-induced AD facilitation (d-ADF) is
      blocked by the specific Kv1.1 channel blocker dendrotoxin-K. Using fast voltage
      imaging of the axon, we show that somatic depolarization used for induction of d
      ADF broadened the AP in the axon through inactivation of Kv1.1 channels. Somatic
      depolarization enhanced spike-evoked calcium signals in presynaptic terminals,
      but not basal calcium. In conclusion, axonal Kv1.1 channels determine glutamate
      release in CA3 neurons in a time-dependent manner through the control of the
      presynaptic spike waveform. 

PMID- 25394684
TI  - Serum cortisol concentrations during induced hypothermia for perinatal asphyxia
      are associated with neurological outcome in human infants.
AB  - Birth asphyxia is a cause of neonatal death or adverse neurological sequelae.
      Biomarkers can be useful to clinicians in order to optimize intensive care
      management and communication of prognosis to parents. During perinatal adverse
      events, increased cortisol secretion is due to hypothalamo-pituitary-adrenal axis
      activation. We aimed to investigate if cortisol variations during therapeutic
      hypothermia are associated with neurodevelopmental outcome. We compared 18 cases
      (neonates with birth asphyxia) with 18 controls (healthy term newborns) and
      confirmed increased serum cortisol concentrations following the peri-partum
      adverse event. Among cases, we stratified patients according to neurological
      outcome at 18 months (group A - good; group B - adverse) and found that after 24
      h of therapeutic hypothermia serum cortisol concentration was significantly lower
      in group A vs group B (28.7 ng/mL vs 344 ng/mL, *p = 0.01). In group B serum,
      cortisol concentration decreased more gradually during therapeutic hypothermia.
      We conclude that monitoring serum cortisol concentration during neonatal
      therapeutic hypothermia can add information to clinical evaluation of neonates
      with birth asphyxia; cortisol values after the first 24 h of hypothermia can be a
      biomarker associated with neurodevelopmental outcome at 18 months of age.

PMID- 25394685
TI  - Over-limiting current and control of dendritic growth by surface conduction in
      nanopores.
AB  - Understanding over-limiting current (faster than diffusion) is a long-standing
      challenge in electrochemistry with applications in desalination and energy
      storage. Known mechanisms involve either chemical or hydrodynamic instabilities
      in unconfined electrolytes. Here, it is shown that over-limiting current can be
      sustained by surface conduction in nanopores, without any such instabilities, and
      used to control dendritic growth during electrodeposition. Copper electrodeposits
      are grown in anodized aluminum oxide membranes with polyelectrolyte coatings to
      modify the surface charge. At low currents, uniform electroplating occurs,
      unaffected by surface modification due to thin electric double layers, but the
      morphology changes dramatically above the limiting current. With negative surface
      charge, growth is enhanced along the nanopore surfaces, forming surface dendrites
      and nanotubes behind a deionization shock. With positive surface charge,
      dendrites avoid the surfaces and are either guided along the nanopore centers or
      blocked from penetrating the membrane. 

PMID- 25394686
TI  - Secretion of small/microRNAs including miR-638 into extracellular spaces by
      sphingomyelin phosphodiesterase 3.
AB  - A recent study demonstrated that intracellular small/microRNAs are released from
      cells, and some of these extracellular RNAs are embedded in vesicles, such as
      ceramide-rich exosomes, on lipid-bilayer membranes. In the present study, we
      examined the effects of sphingomyelin phosphodiesterase 3 (SMPD3), which
      generates ceramide from sphingomyelin, on the release of small/microRNAs from
      intracellular to extracellular spaces. In these experiments, SW480 human
      colorectal and HuH-7 human hepatocellular cancer cells were cultured for 48 h in
      serum-free media. Culture supernatants were then collected, and floating cells
      and debris were removed by centrifugation and filtration through a 0.22-um
      filter. Extracellular small RNAs in purified culture supernatants were stable for
      4 weeks at room temperature, after 20 freeze-thaw cycles and exposure to pH 2.0,
      and were resistant to ribonuclease A degradation. Amino acid sequence analyses of
      SMPD3 showed high homology between mammals, indicating evolutionary conservation.
      Therefore, to investigate the mechanisms of cellular small/microRNA export, SW480
      and HuH-7 cells were treated with the SMPD3 inhibitor GW4869 in serum-free media.
      Culture supernatants were collected for microarray and/or reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) experiments. The number of
      microRNAs in culture supernatants was decreased following treatment with GW4869.
      Among these, extracellular and intracellular miR-638 were dose-dependently
      decreased and increased, respectively. These data suggest that SMPD3 plays an
      important role in the release of microRNAs into extracellular spaces.

PMID- 25394687
TI  - Factors related to the need for surgical reconstruction after anterior cruciate
      ligament rupture: a systematic review of the literature.
AB  - STUDY DESIGN: Systematic literature review. OBJECTIVES: To summarize and evaluate
      research on factors predictive of progression to surgery after nonoperative
      treatment for an anterior cruciate ligament (ACL) rupture. BACKGROUND: Anterior
      cruciate ligament rupture is a common injury among young, active individuals.
      Surgical reconstruction is often required for patients who do not regain
      satisfactory knee function following nonsurgical rehabilitation. Knowledge of
      factors that predict the need for surgical reconstruction of the ACL would be
      helpful to guide the decision-making process in this population. METHODS: A
      search was performed for studies predicting the need for surgery after
      nonoperative treatment for ACL rupture in the Embase, MEDLINE (OvidSP), Web of
      Science, CINAHL, Cochrane Central Register of Controlled Trials, PubMed, and
      Google Scholar digital databases from inception to October 2013. Two reviewers
      independently selected the studies and performed a quality assessment. Best
      evidence synthesis was used to summarize the evidence of factors predicting the
      need for surgical reconstruction after nonoperative treatment for an ACL rupture.
      RESULTS: Seven studies were included, 3 of which were of high quality. Based on
      these studies, neither sex (strong evidence) nor the severity of knee joint
      laxity (moderate evidence) can predict whether, soon after ACL injury, a patient
      will need ACL reconstruction following nonoperative treatment. All other factors
      identified in this review either had conflicting or only minimal evidence as to
      their level of association with the need for surgical reconstruction. Noteworthy
      is that 1 high-quality study reported that the spherical shape of the femoral
      condyle was predictive of the need for ACL reconstruction. CONCLUSION: Sex and
      knee joint laxity tests do not predict the need for ACL reconstruction soon after
      an ACL rupture. Independent validation in future research will be necessary to
      establish whether knee shape is a predictive factor. LEVEL OF EVIDENCE:
      Prognosis, level 1a-.

PMID- 25394688
TI  - Validity of the QuickDASH in patients with shoulder-related disorders undergoing
      surgery.
AB  - STUDY DESIGN: Validity study. OBJECTIVE: To determine the validity of the
      shortened version of the Disabilities of the Arm, Shoulder and Hand questionnaire
      (QuickDASH) in comparison to the full DASH in patients undergoing total shoulder
      arthroplasty (TSA) and rotator cuff repair (RCR). BACKGROUND: The QuickDASH is a
      shorter version of the DASH that may reduce respondent burden while retaining
      similar measurement properties. METHODS: One hundred thirty-two patients
      undergoing TSA or RCR were assessed at baseline and at 3 and 6 months
      postoperatively. The patients completed the DASH, American Shoulder and Elbow
      Surgeons Standardized Shoulder Assessment Form self-report section, and the
      Western Ontario Rotator Cuff index, and were tested to determine their shoulder
      range of motion and isometric strength. The differences between scores on the
      DASH and QuickDASH across the scale range were evaluated using the Bland-Altman
      technique. Item difficulty, correlations with other patient-reported outcome
      measures, and physical impairments were used to assess validity. Known group
      validity was assessed by examining differentiation of work status. Responsiveness
      was assessed through standardized response means. RESULTS: QuickDASH scores were
      slightly higher than DASH scores, with a mean difference of 1 to 1.3 points for
      the TSA group and 1 to 3 points for the RCR group tested preoperatively, and at 3
      months and 6 months postoperatively, although limits of agreement were wide
      (ranging from -10 to 13 across all estimates). The QuickDASH items were
      distributed across the full DASH, when ranked by item difficulty, for both
      patient groups. The correlation between the QuickDASH and DASH was almost perfect
      (r>0.92). Correlations between the DASH/QuickDASH and other patient-reported
      outcome measures ranged from moderate to very large (American Shoulder and Elbow
      Surgeons Standardized Shoulder Assessment Form self-report section, r=0.47-0.85;
      Western Ontario Rotator Cuff index, r=0.83-0.91), whereas correlations to
      impairments were small to moderate. Correlation estimates varied by less than
      0.07, depending on whether the DASH or QuickDASH was used, suggesting equivalent
      construct validity. Both the DASH and QuickDASH discriminated between working and
      nonworking patients, with similar group differences and statistical significance
      (P<.01). The QuickDASH and DASH showed similar responsiveness between presurgery
      and 6-month follow-up (standardized response mean, 1.1 following TSA and 0.8
      following RCR). CONCLUSION: When substituting the QuickDASH for the full DASH,
      similar score estimates, discrimination of clinically relevant subgroups, and
      responsiveness can be expected across patients following TSA and RCR.

PMID- 25394689
TI  - Translation, cross-cultural adaptation, and psychometric properties of the German
      version of the hip disability and osteoarthritis outcome score.
AB  - STUDY DESIGN: Clinical measurement. OBJECTIVES: To translate and cross-culturally
      adapt the Hip disability and Osteoarthritis Outcome Score (HOOS) from English
      into German, and to study its psychometric properties in patients after hip
      surgery. BACKGROUND: There is no specific hip questionnaire in German that not
      only measures symptoms and function but also contains items about hip-related
      quality of life. METHODS: The translation and cross-cultural adaptation involved
      forward translation, harmonization, cognitive debriefing, back translation, and
      comparison to the original HOOS following international guidelines. The German
      version was tested in 51 Swiss inpatients 8 weeks after different types of hip
      surgery, mainly total hip replacement. The mean age of the participants was 62.5
      years, and the age range was from 27 to 87 years. Thirty (58.8%) of the
      participants were women. Internal consistency and test-retest reliability were
      estimated using Cronbach alpha and intraclass correlation coefficients for
      agreement. For construct validity, total scores of the German HOOS were
      correlated with those of the Western Ontario and McMaster Universities
      Osteoarthritis Index. The HOOS was also compared to the Medical Outcomes Study 36
      Item Short-Form Health Survey. RESULTS: Cronbach alpha values for all German HOOS
      subscales were between .87 and .93. For test-retest reliability, the intraclass
      correlation coefficient for agreement was 0.85 for the total scores of the German
      HOOS. The Spearman rho for the Medical Outcomes Study 36-Item Short-Form Health
      Survey physical functioning subscale compared to the sum of all HOOS subscales
      was 0.71, and that for the Medical Outcomes Study 36-Item Short-Form Health
      Survey physical component summary was 0.97. CONCLUSION: The German HOOS has
      demonstrated adequate reliability and validity. Use of the German HOOS is
      recommended for assessment of patients after hip surgery, with the proviso that
      additional psychometric testing should be done in future research.

PMID- 25394690
TI  - Test-retest and interrater reliability of the functional lower extremity
      evaluation.
AB  - STUDY DESIGN: Repeated-measures clinical measurement reliability study.
      OBJECTIVES: To establish the reliability and face validity of the Functional
      Lower Extremity Evaluation (FLEE). BACKGROUND: The FLEE is a 45-minute battery of
      8 standardized functional performance tests that measures 3 components of lower
      extremity function: control, power, and endurance. The reliability and normative
      values for the FLEE in healthy athletes are unknown. METHODS: A face validity
      survey for the FLEE was sent to sports medicine personnel to evaluate the level
      of importance and frequency of clinical usage of each test included in the FLEE.
      The FLEE was then administered and rated for 40 uninjured athletes. To assess
      test-retest reliability, each athlete was tested twice, 1 week apart, by the same
      rater. To assess interrater reliability, 3 raters scored each athlete during 1 of
      the testing sessions. Intraclass correlation coefficients were used to assess the
      test-retest and interrater reliability of each of the FLEE tests. RESULTS: In the
      face validity survey, the FLEE tests were rated as highly important by 58% to 71%
      of respondents but frequently used by only 26% to 45% of respondents. Interrater
      reliability intraclass correlation coefficients ranged from 0.83 to 1.00, and
      test-retest reliability ranged from 0.71 to 0.95. CONCLUSION: The FLEE tests are
      considered clinically important for assessing lower extremity function by sports
      medicine personnel but are underused. The FLEE also is a reliable assessment
      tool. Future studies are required to determine if use of the FLEE to make return
      to-play decisions may reduce reinjury rates.

PMID- 25394691
TI  - ''The association of normal tension glaucoma with Buerger's disease: a case
      report''.
AB  - BACKGROUND: To report a case of a 48-year-old man with Buerger's disease who
      presented with bilateral normal-tension glaucoma (NTG). CASE PRESENTATION: A 48
      year-old man who had been diagnosed with Buerger's disease 12 years ago, and
      received bilateral below-the-knee amputations for ischemic ulcers of the lower
      limbs, presented at our clinic due to a sudden loss of visual acuity in the left
      eye. A fundus exam revealed a cup-to-disc ratio of 0.5 for the right eye and 0.8
      for the left eye, arteriolar constriction in both eyes, retinal edema in the
      inferopapillary area, and splinter hemorrhages and soft exudate in the left eye.
      We diagnosed the patient as having acute nasal branch retinal artery occlusion in
      the left eye and bilateral NTG, as a result of the ophthalmologic examination and
      the other findings. CONCLUSION: Although the pathomechanism of NTG is still
      unknown, previous studies have suggested that patients with NTG show a higher
      prevalence of vasospastic disorders. We present the second report of NTG
      associated with Buerger's disease to be described in the literature.

PMID- 25394693
TI  - Erratum to: Time seizures and the self: institutional temporalities and self
      preservation among homeless women.

PMID- 25394692
TI  - Effects of omega-3 on metabolic markers in postmenopausal women with metabolic
      syndrome.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of diet alone or
      combined with omega-3 supplementation on metabolic and inflammatory markers in
      postmenopausal women with metabolic syndrome. METHODS: This randomized,
      controlled trial included 87 Brazilian women (age >= 45 years and with amenorrhea
      >= 12 months). Exclusion criteria were: cardiovascular disease, insulin-dependent
      diabetes, cancer, autoimmune diseases and use of either statins or hormone
      therapy. Participants were randomized to diet alone (n = 43, control) or diet
      plus omega-3 supplementation, 900 mg/day orally (n = 44). All women were provided
      with an individualized dietary prescription. Clinical, anthropometrical (body
      mass index and waist circumference) and biochemical variables were measured. The
      inflammatory profile included C-reactive protein, tumor necrosis factor alpha and
      interleukins (IL-1beta and IL-6). The intervention time was 6 months, with
      assessments at initiation and completion. Data were analyzed according to
      intention-to-treat, using the independent t-test and ANOVA. RESULTS: There were
      significant reductions in body mass index and waist circumference in both groups
      (p < 0.05) without significant changes in body fat or muscle mass. Intervention
      with diet plus omega-3 was associated with significant reduction in systolic (<
      12.2%) and diastolic (< 8.2%) blood pressure, serum triglyceride concentration (<
      21.4%), and insulin resistance (< 13.1%) (p < 0.05), as well as a reduction in
      serum IL-6 concentration (< 28.5%) (p = 0.034). CONCLUSION: In postmenopausal
      women with metabolic syndrome, dietary intervention plus supplementation of omega
      3 resulted in a further decrease in triglycerides and blood pressure and also in
      an improvement in insulin resistance and inflammatory markers, important
      components of metabolic syndrome.

PMID- 25394694
TI  - Music as Illness; Music as Healing.
AB  - Throughout the Soviet Union, the arts became tied to ethnicity through the
      project of Socialist Realism. When, in 1991, the Kyrgyz Republic became
      independent from the Soviet Union, its national narrative continued to be built
      upon tropes of Kyrgyz ethnicity. Through their engagement with images of the
      ethno-national self, the arts provide a great source of beauty. Defining beauty
      as a representation of the self that is pure whole, and stable, Julia Kristeva
      asserts that beauty and suffering are part of the same phenomena. Arthur Kleinman
      argues that suffering is best understood as existing within the triangulated
      relationship of cultural representation, collective experience, and subjectivity.
      Music too is part of this triangulated relationship, and therefore, a part of
      suffering. Drawing upon ten months of ethnographic fieldwork in Kyrgyzstan, this
      article explores the illness experience of a single Kyrgyz musician. In doing so,
      it illustrates music's role in self-formation and the development of social,
      economic, and political ties and the shifts that occur in these during illness.
      In drawing forth the role of music in the construction of racialized ethnicities,
      this article demonstrates how the experience of transformative beauty can coexist
      with turmoil, marginalization, and violence. 

PMID- 25394695
TI  - Psychiatry with teeth: notes on coercion and control in France and the United
      States.

PMID- 25394696
TI  - Determination of sterigmatocystin in grain using gas chromatography-mass
      spectrometry with an on-column injector.
AB  - Sterigmatocystin (STC) is a mycotoxin produced by several species of Aspergillus
      and other fungi. STC is a precursor of the carcinogen aflatoxin B1 and exerts
      carcinogenic, teratogenic, and mutagenic effects. A reliable GC-MS-based
      analytical method using on-column injection was developed and validated to
      determine STC content in grain. In this method, STC was extracted with
      acetonitrile (84%), and the filtered extract was diluted with phosphate buffer
      before immunoaffinity column (IAC) cleanup. After elution and N2 evaporation, the
      sample containing STC was dissolved in acetone and injected into the GC-MS system
      without derivatization. Separation of STC was carried out by a capillary column
      (0.25 mm i.d.*30 m, 0.25 MUm) with a deactivated pre-column (0.53 mm i.d.*0.6 m).
      The matrix effect was investigated in maize, wheat, and rice, and an
      insignificant matrix effect was observed after IAC cleanup. The calibration curve
      was linear in the range of 20-300 pg (equivalent to 8-120 MUg/kg in grain) with a
      coefficient of determination (R2) of 0.999, and the relative standard deviation
      of repeatability (RSDr) was less than 10 %. The limit of detection (LOD) of the
      method was 6 pg (equivalent to 2.4 MUg/kg in grain), and the limit of
      quantification (LOQ) was 20 pg (equivalent to 8 MUg/kg). The method described in
      this report is sensitive, reliable, and can be used to monitor STC contamination
      in grain.

PMID- 25394697
TI  - Snippet.

PMID- 25394698
TI  - Placebos in regional anaesthesia research.

PMID- 25394699
TI  - Using Jaques Nelaton catheter as an introducer for nasotracheal intubation.

PMID- 25394700
TI  - Editor-in-Chief's reply.

PMID- 25394701
TI  - Trismus and the limits of laryngoscopy.

PMID- 25394702
TI  - Disposable C-MAC((r)) videolaryngoscope blade - not the same as the re-usable
      blade.

PMID- 25394703
TI  - Femoral nerve block dose after hip fracture.

PMID- 25394704
TI  - Another difficult neonatal intubation using a disposable laryngoscope blade.

PMID- 25394705
TI  - A reply.

PMID- 25394706
TI  - Ulnar 'dive' identification of the median nerve in the forearm.

PMID- 25394707
TI  - Cytological detection of fat globules after embolism.

PMID- 25394708
TI  - Histoacryl((r)) for securing central venous catheters: not so sticky!

PMID- 25394709
TI  - Teaching novice anaesthetists.

PMID- 25394710
TI  - Development of a lack of appetite item bank for computer-adaptive testing (CAT).
AB  - PURPOSE: A significant proportion of oncological patients experiences lack of
      appetite. Precise measurement is relevant to improve the management of lack of
      appetite. The so-called computer-adaptive test (CAT) allows for adaptation of the
      questionnaire to the individual patient, thereby optimizing measurement
      precision. The EORTC Quality of Life Group is developing a CAT version of the
      widely used EORTC QLQ-C30 questionnaire. Here, we report on the development of
      the lack of appetite CAT. METHODS: The EORTC approach to CAT development
      comprises four phases: literature search, operationalization, pre-testing, and
      field testing. Phases 1-3 are described in this paper. First, a list of items was
      retrieved from the literature. This was refined, deleting redundant and
      irrelevant items. Next, new items fitting the "QLQ-C30 item style" were created.
      These were evaluated by international samples of experts and cancer patients.
      RESULTS: The literature search generated a list of 146 items. After a
      comprehensive item selection procedure, the list was reduced to 24 items. These
      formed the basis for 21 new items fitting the QLQ-C30 item style. Expert
      evaluations (n = 10) and patient interviews (n = 49) reduced the list to 12 lack
      of appetite items. CONCLUSIONS: Phases 1-3 resulted in 12 lack of appetite
      candidate items. Based on a field testing (phase 4), the psychometric
      characteristics of the items will be assessed and the final item bank will be
      generated. This CAT item bank is expected to provide precise and efficient
      measurement of lack of appetite while still being backward compatible to the
      original QLQ-C30 scale.

PMID- 25394711
TI  - Supportive care needs and preferences of lung cancer patients: a semi-structured
      qualitative interview study.
AB  - PURPOSE: Lung cancer patients report both high levels of unmet supportive care
      need and underutilisation of support services, but the existing literature offers
      limited understanding of their specific needs and preferences for help. This
      study aimed to address this research gap through qualitative exploration of the
      supportive care needs and preferences of lung cancer patients. METHODS: Semi
      structured interviews were conducted with ten lung cancer patients recruited from
      the Chest Clinic, Royal Adelaide Hospital (South Australia). Interviews
      particularly focussed on four key supportive care domains: medical information,
      physical symptoms, activities of daily living and emotional needs. RESULTS:
      Participants reported low use of supportive care services and resources in all
      four domains. Verbal information from doctors was preferred over printed or
      online information, and upfront and honest communication was highly valued.
      Attitude was viewed as important for coping with physical symptoms. Participants
      demonstrated strong determination to manage activities of daily living
      independently and, when this was not possible, preferred to seek help from family
      over external organisations. Support groups and helplines were not utilised for a
      variety of reasons, although several benefits of connecting with fellow cancer
      patients were identified. CONCLUSIONS: The reasons behind underutilisation of
      supportive care services by lung cancer patients are more complex than simple
      lack of awareness or availability of services. Information about patients' needs
      and preferences reveals opportunities for service improvement and alternative
      models of supportive care.

PMID- 25394713
TI  - GAPDH enhances the aggressiveness and the vascularization of non-Hodgkin's B
      lymphomas via NF-kappaB-dependent induction of HIF-1alpha.
AB  - Deregulated expression of glycolytic enzymes contributes not only to the
      increased energy demands of transformed cells but also has non-glycolytic roles
      in tumors. However, the contribution of these non-glycolytic functions in tumor
      progression remains poorly defined. Here, we show that elevated expression of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but not of other glycolytic
      enzymes tested, increased aggressiveness and vascularization of non-Hodgkin's
      lymphoma. Elevated GAPDH expression was found to promote nuclear factor-kappaB
      (NF-kappaB) activation via binding to tumor necrosis factor receptor-associated
      factor-2 (TRAF2), enhancing the transcription and the activity of hypoxia
      inducing factor-1alpha (HIF-1alpha). Consistent with this, inactive mutants of
      GAPDH failed to bind TRAF2, enhance HIF-1 activity or promote lymphomagenesis.
      Furthermore, elevated expression of gapdh mRNA in biopsies from diffuse large B
      cell non-Hodgkin's lymphoma patients correlated with high levels of hif-1alpha,
      vegf-a, nfkbia mRNA and CD31 staining. Collectively, these data indicate that
      deregulated GAPDH expression promotes NF-kappaB-dependent induction of HIF-1alpha
      and has a key role in lymphoma vascularization and aggressiveness. 

PMID- 25394714
TI  - PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active
      against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I
      mutation.
AB  - Targeting BCR/ABL with tyrosine kinase inhibitors (TKIs) is a proven concept for
      the treatment of Philadelphia chromosome-positive (Ph+) leukemias. Resistance
      attributable to either kinase mutations in BCR/ABL or nonmutational mechanisms
      remains the major clinical challenge. With the exception of ponatinib, all
      approved TKIs are unable to inhibit the 'gatekeeper' mutation T315I. However, a
      broad spectrum of kinase inhibition increases the off-target effects of TKIs and
      may be responsible for cardiovascular issues of ponatinib. Thus, there is a need
      for more selective options for the treatment of resistant Ph+ leukemias. PF-114
      is a novel TKI developed with the specifications of (i) targeting T315I and other
      resistance mutations in BCR/ABL; (ii) achieving a high selectivity to improve
      safety; and (iii) overcoming nonmutational resistance in Ph+ leukemias. PF-114
      inhibited BCR/ABL and clinically important mutants including T315I at nanomolar
      concentrations. It suppressed primary Ph+ acute lymphatic leukemia-derived long
      term cultures that either displayed nonmutational resistance or harbor the T315I.
      In BCR/ABL- or BCR/ABL-T315I-driven murine leukemia as well as in xenograft
      models of primary Ph+ leukemia harboring the T315I, PF-114 significantly
      prolonged survival to a similar extent as ponatinib. Our work supports clinical
      evaluation of PF-114 for the treatment of resistant Ph+ leukemia. 

PMID- 25394716
TI  - Bilateral auricular involvement: a rare presenting sign of chronic lymphocytic
      leukemia, and successful treatment with electron beam therapy.

PMID- 25394715
TI  - Myelodysplasia is in the niche: novel concepts and emerging therapies.
AB  - Myelodysplastic syndromes (MDSs) represent clonal disorders mainly of the elderly
      that are characterized by ineffective hematopoiesis and an increased risk of
      transformation into acute myeloid leukemia. The pathogenesis of MDS is thought to
      evolve from accumulation and selection of specific genetic or epigenetic events.
      Emerging evidence indicates that MDS is not solely a hematopoietic disease but
      rather affects the entire bone marrow microenvironment, including bone
      metabolism. Many of these cells, in particular mesenchymal stem and progenitor
      cells (MSPCs) and osteoblasts, express a number of adhesion molecules and
      secreted factors that regulate blood regeneration throughout life by contributing
      to hematopoietic stem and progenitor cell (HSPC) maintenance, self-renewal and
      differentiation. Several endocrine factors, such as erythropoietin, parathyroid
      hormone and estrogens, as well as deranged iron metabolism modulate these
      processes. Thus, interactions between MSPC and HSPC contribute to the
      pathogenesis of MDS and associated pathologies. A detailed understanding of these
      mechanisms may help to define novel targets for diagnosis and possibly therapy.
      In this review, we will discuss the scientific rationale of 'osteohematology' as
      an emerging research field in MDS and outline clinical implications. 

PMID- 25394717
TI  - Prenatal extra-abdominal bowel dilatation is a risk factor for intrapartum fetal
      compromise for fetuses with gastroschisis.
AB  - OBJECTIVE: The aim of this study was to investigate the prenatal ultrasound
      features that were associated with intrapartum fetal distress in fetuses with
      gastroschisis. METHODS: This was a retrospective observational study of all cases
      of gastroschisis referred to and delivering at the Mater Mothers' Hospital in
      Brisbane, Australia. Maternal demographics, prenatal ultrasound features
      including the presence of bowel dilatation, umbilical artery and middle cerebral
      artery Doppler indices and amniotic fluid volume as well as intrapartum outcome
      details were analysed using univariate and multivariate logistic regression to
      ascertain factors predictive of intrapartum compromise. RESULTS: The study cohort
      included 155 cases of gastroschisis over a 16-year period. The overall perinatal
      loss rate was 5.9% (four intrauterine fetal deaths, four neonatal deaths and one
      termination of pregnancy). The live birth rate was 96.8% (150/155). Fetal heart
      rate abnormalities occurred in 55.1% of cases. The overall caesarean section rate
      was 40.9% (63/154), of which 63.5% (40/63) was emergency procedures. Both
      univariate and multivariate analysis confirmed that only extra-abdominal bowel
      dilatation was a risk factor for intrapartum fetal compromise necessitating
      emergency delivery. CONCLUSIONS: Extra-abdominal bowel dilatation is a risk
      factor for intrapartum fetal compromise (OR 2.2; 95%CI 1.03-4.7) and emergent
      delivery.

PMID- 25394718
TI  - Genetic and phenotypic characterization of a hybrid zone between polyandrous
      Northern and Wattled Jacanas in Western Panama.
AB  - BACKGROUND: Hybridization provides a unique perspective into the ecological,
      genetic and behavioral context of speciation. Hybridization is common in birds,
      but has not yet been reported among bird species with a simultaneously
      polyandrous mating system; a mating system where a single female defends a harem
      of males who provide nearly all parental care. Unlike simple polyandry,
      polyandrous mating is extremely rare in birds, with only 1% of bird species
      employing this mating system. Although it is classically held that females are
      "choosy" in avian hybrid systems, nearly-exclusive male parental care raises the
      possibility that female selection against heterospecific matings might be reduced
      compared to birds with other mating systems. RESULTS: We describe a narrow hybrid
      zone in southwestern Panama between two polyandrous freshwater waders: Northern
      Jacana, Jacana spinosa and Wattled Jacana, J. jacana. We document coincident
      cline centers for three phenotypic traits, mtDNA, and one of two autosomal
      introns. Cline widths for these six markers varied from seven to 142 km, with
      mtDNA being the narrowest, and five of the six markers having widths less than
      100 km. Cline tails were asymmetrical, with greater introgression of J. jacana
      traits extending westward into the range of J. spinosa. Likewise, within the
      hybrid zone, the average hybrid index of phenotypic hybrids was significantly
      biased towards J. spinosa. Species distribution models indicate that the hybrid
      zone is located at the edge of a roughly 100 km wide overlap where habitat is
      predicted to be suitable for both species, with more westerly areas suitable only
      for spinosa and eastward habitats suitable only for J. jacana. CONCLUSION: The
      two species of New World jacanas maintain a narrow, and persistent hybrid zone in
      western Panama. The hybrid zone may be maintained by the behavioral dominance of
      J. spinosa counterbalanced by unsuitable habitat for J. spinosa east of the
      contact zone. Although the two parental species are relatively young,
      mitochondrial cline width was extremely narrow. This result suggests strong
      selection against maternally-inherited markers, which may indicate either
      mitonuclear incompatibilities and/or female choice against heterospecific matings
      typical of avian hybrid systems, despite jacana sex role reversal.

PMID- 25394719
TI  - The first two cases of MYH9 disorders in Thailand: an international collaborative
      study.

PMID- 25394720
TI  - Remission induction with lenalidomide in a patient with relapsed diffuse large B
      cell lymphoma of the leg type.

PMID- 25394721
TI  - The assessment and treatment of back and neck pain: an initial investigation in a
      primary care practice-based research network.
AB  - AIM: The purpose of this study was to conduct an exploratory examination of the
      current state of non-malignant acute and chronic back and neck pain assessment
      and management among primary care providers in a multi-site, practice-based
      research network. BACKGROUND: Acute and chronic pain are distinct conditions that
      often require different assessment and management approaches, however, little
      research has examined assessment and management of acute and chronic pain as
      separate conditions. The large majority of patients with acute and chronic back
      and neck pain are managed in primary care settings. Given the differences between
      acute and chronic pain, it is necessary to identify differences in patient
      characteristics, practitioner evaluation, treatment and management in primary
      care settings. METHODS: Over a two-week period, 24 practitioners in a multi-site
      practice-based research network completed 196 data cards about 39 patients
      experiencing acute back and neck pain and 157 patients suffering from chronic
      back and neck pain. Findings There were significant differences between the
      patients experiencing acute and chronic pain in regards to practitioner
      evaluation, current medication management and current treatment for depression.
      In addition, diagnostics differed between patients experiencing acute versus
      chronic back and neck pain. Further, primary care providers' review of online
      drug monitoring program reports during the current visit was associated with
      current medication management using short term opioids, long-term opioids or
      tramadol. Most research examining acute and chronic pain focuses on the low back.
      Additional research needs to be conducted to explore and compare acute and
      chronic pain across the whole spine.

PMID- 25394722
TI  - Administration of low doses of IL-2 combined to rapamycin promotes allogeneic
      skin graft survival in mice.
AB  - Human CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) prevent allogeneic graft
      rejection by inhibiting T cell activation, as has been shown in mouse models.
      Recently, low-dose IL-2 administration was shown to specifically activate Tregs
      but not pathogenic conventional T cells, leading to resolution of type 1 diabetes
      in nonobese diabetic mice. We therefore tested the ability of low-dose IL-2 to
      prevent allogeneic skin graft rejection. We found that while IL-2 alone was
      inefficient in preventing rejection, combined with rapamycin, IL-2 treatment
      promoted skin graft survival both in minor disparate and semi-allogeneic skin
      graft combinations. Tregs are activated by this combined treatment while
      conventional CD4(+) cell expansion and activation are markedly inhibited. Co
      administration of anti-CD25 antibodies dramatically reduces the effect of the IL
      2/rapamycin treatment, strongly supporting a central role for Treg activation.
      Thus, we provide the first preclinical data showing that low-dose IL-2 combined
      with rapamycin can significantly delay transplant rejection in mice. These
      findings may form the rational for clinical evaluation of this novel approach for
      the prevention of transplant rejection. 

PMID- 25394723
TI  - Geomicrobial ecotoxicology as a new subject in environmental sciences is
      proposed.
AB  - Environmental sciences is an interdisciplinary subject and current development
      allows investigation of environmental issues from physical, chemical, geological,
      biological and toxicological approaches. Based on such development, geomicrobial
      ecotoxicology or microbial ecotoxicology is proposed to advance the information
      gathering on ecosystem processes and function because microorganisms are numerous
      and fundamental to the cycling of nutrients and energy flow. 

PMID- 25394724
TI  - The role of maternal-specific H3K9me3 modification in establishing imprinted X
      chromosome inactivation and embryogenesis in mice.
AB  - Maintaining a single active X-chromosome by repressing Xist is crucial for
      embryonic development in mice. Although the Xist activator RNF12/RLIM is present
      as a maternal factor, maternal Xist (Xm-Xist) is repressed during preimplantation
      phases to establish imprinted X-chromosome inactivation (XCI). Here we show,
      using a highly reproducible chromatin immunoprecipitation method that facilitates
      chromatin analysis of preimplantation embryos, that H3K9me3 is enriched at the
      Xist promoter region, preventing Xm-Xist activation by RNF12. The high levels of
      H3K9me3 at the Xist promoter region are lost in embryonic stem (ES) cells, and ES
      cloned embryos show RNF12-dependent Xist expression. Moreover, lack of Xm-XCI in
      the trophectoderm, rather than loss of paternally expressed imprinted genes, is
      the primary cause of embryonic lethality in 70-80% of parthenogenotes immediately
      after implantation. This study reveals that H3K9me3 is involved in the imprinting
      that silences Xm-Xist. Our findings highlight the role of maternal-specific
      H3K9me3 modification in embryo development. 

PMID- 25394725
TI  - The improved accuracy of planar bone scintigraphy by adding single photon
      emission computed tomography (SPECT-CT) to detect skeletal metastases from
      prostate cancer.
AB  - BACKGROUND: Planar bone scintigraphy (PBS) is a standard radiological technique
      to detect skeletal metastases from prostate cancer (PC), the addition of SPECT-CT
      to PBS improves its diagnostic accuracy. The aim of this study was to assess the
      additional value of targeted SPECT-CT with PBS in detecting skeletal metastasis
      form prostate cancer, considering resource implications in an Irish hospital
      setting. METHODS: 54 PC patients with increased radiotracer uptake on PBS were
      retrospectively recruited from 2012 to 2013. All underwent targeted evaluation
      with SPECT-CT. PBS and SPECT-CT images were reviewed by two nuclear medicine
      radiologists and reported independently. The final diagnosis was made based on
      the CT finding corresponding to the area of radiotracer uptake. RESULTS: The mean
      age was 70.9 years (48-88 years) and median PSA at presentation was 13.9 ng/ml
      (4.2-215 ng/ml). 68.5 % (n = 37) men received treatment for PC while 31.5 % (n =
      17) patients had not received treatment prior to PBS. 164 areas of increased
      radiotracer uptake were identified on PBS; 13 areas were characterised as
      metastatic on SPECT-CT; iliac bone (n = 3), ribs (n = 1), skull (n = 2), sacrum
      (n = 1), ischium (n = 1), femur (n = 3), thoracic spine (n = 1) and cervical
      spine (n = 1). 151 areas were characterised as benign on SPECT-CT. One area of
      increased radiotracer uptake in the ribs was subsequently described as
      indeterminate after evaluation with SPECT-CT. CONCLUSION: SPECT-CT improves the
      diagnostic accuracy of PBS in detecting skeletal metastasis from PC and is
      superior to PBS alone in differentiating benign from malignant lesions.
      Notwithstanding resource implications of increased cost, specialist equipment and
      specialist manpower hours; we recommend the use of SPECT-CT in conjunction with
      PBS for targeted evaluation of suspicious bony lesions in this cohort of
      patients.

PMID- 25394726
TI  - Truncating mutations in the last exon of NOTCH3 cause lateral meningocele
      syndrome.
AB  - Lateral meningocele syndrome (LMS, OMIM%130720), also known as Lehman syndrome,
      is a very rare skeletal disorder with facial anomalies, hypotonia and meningocele
      related neurologic dysfunction. The characteristic lateral meningoceles represent
      the severe end of the dural ectasia spectrum and are typically most severe in the
      lower spine. Facial features of LMS include hypertelorism and telecanthus, high
      arched eyebrows, ptosis, midfacial hypoplasia, micrognathia, high and narrow
      palate, low-set ears and a hypotonic appearance. Hyperextensibility, hernias and
      scoliosis reflect a connective tissue abnormality, and aortic dilation, a high
      pitched nasal voice, wormian bones and osteolysis may be present. Lateral
      meningocele syndrome has phenotypic overlap with Hajdu-Cheney syndrome. We
      performed exome resequencing in five unrelated individuals with LMS and
      identified heterozygous truncating NOTCH3 mutations. In an additional unrelated
      individual Sanger sequencing revealed a deleterious variant in the same exon 33.
      In total, five novel de novo NOTCH3 mutations were identified in six unrelated
      patients. One had a 26 bp deletion (c.6461_6486del, p.G2154fsTer78), two carried
      the same single base pair insertion (c.6692_93insC, p.P2231fsTer11), and three
      individuals had a nonsense point mutation at c.6247A > T (pK2083*), c.6663C > G
      (p.Y2221*) or c.6732C > A, (p.Y2244*). All mutations cluster into the last coding
      exon, resulting in premature termination of the protein and truncation of the
      negative regulatory proline-glutamate-serine-threonine rich PEST domain. Our
      results suggest that mutant mRNA products escape nonsense mediated decay. The
      truncated NOTCH3 may cause gain-of-function through decreased clearance of the
      active intracellular product, resembling NOTCH2 mutations in the clinically
      related Hajdu-Cheney syndrome and contrasting the NOTCH3 missense mutations
      causing CADASIL.

PMID- 25394727
TI  - Plasmon-induced photoluminescence immunoassay for tuberculosis monitoring using
      gold-nanoparticle-decorated graphene.
AB  - Metal-nanoparticle-functionalized graphene, in particular, graphene sheets
      containing Au nanoparticles (Au NPs), have generated considerable interest
      because of their unique optical and electrical characteristics. In this study, we
      successfully produced graphene sheets decorated with Au NPs (AuGrp) using
      phytochemicals as reducing agents. During this reaction, Au ions intercalated
      into the layered graphene flakes and were then reduced into NPs, exfoliating the
      graphene sheets. The physicochemical properties of the AuGrp nanocomposites were
      characterized, and the exfoliation process was investigated using a molecular
      dynamics simulation of Au NPs between graphene sheets. Our proposed technique is
      advantageous because the phytochemicals are mild reducing agents that preserve
      the graphene structure during exfoliation and NP decoration. The dispersity of
      the NPs on the graphene sheets was drastically improved due to the use of metal
      ion intercalation. Moreover, the electrical conductivity was 6-30 times higher
      than that of bare graphene and reduced graphene oxide. Using antibody (Ab)
      modified AuGrp sheets and quantum dots, a plasmonic-induced photoluminescence
      immunoassay of tuberculosis (TB) antigen (aG) CFP-10 was demonstrated for a
      potential application of these materials. The enhancement of photoluminescence
      (PL) response was monitored depending on the various TB aG concentrations from
      5.1 pg/mL to 51 MUg/mL, and the detection limit for CFP-10 was 4.5 pg/mL.
      Furthermore, the selectivity was demonstrated with Ag85 as the other TB aG, and
      PL enhancement was not observed in this case. Therefore, AuGrp-based immunoassay
      showed the potential for biosensor application. 

PMID- 25394728
TI  - Obalon intragastric balloon in the treatment of paediatric obesity: a pilot
      study.
AB  - BACKGROUND: Lifestyle interventions are often ineffective in the treatment of
      pediatric obesity. Weight loss devices have been introduced for the temporary
      nonsurgical treatment of morbid obesity. OBJECTIVE: The aim of the study is to
      evaluate the efficacy of Obalon Intragastric Balloon on weight loss and on
      metabolic and cardiovascular parameters in a pediatric population with severe
      obesity. METHODS: We enrolled 10 children with severe obesity. In all patients
      anthropometric parameters, biochemical tests, ultrasound liver examination and
      blood pressure monitoring were evaluated at the time of insertion and after
      removal of device. RESULTS: The Obalon had a positive effect on decrease of
      weight, body mass index and percentage of excess body weight within 3 months from
      placement. Moreover, this safe minimally invasive device improves the cardio
      metabolic profiles of obese children. CONCLUSIONS: The Obalon could be a useful
      tool in the difficult management of pediatric patients with morbid obesity,
      inducing in short-term a meaningful weight loss.

PMID- 25394729
TI  - High-content phenotypic screening and triaging strategy to identify small
      molecules driving oligodendrocyte progenitor cell differentiation.
AB  - Multiple Sclerosis is a demyelinating disease of the CNS and the primary cause of
      neurological disability in young adults. Loss of myelinating oligodendrocytes
      leads to neuronal dysfunction and death and is an important contributing factor
      to this disease. Endogenous oligodendrocyte precursor cells (OPCs), which on
      differentiation are responsible for replacing myelin, are present in the adult
      CNS. As such, therapeutic agents that can stimulate OPCs to differentiate and
      remyelinate demyelinated axons under pathologic conditions may improve neuronal
      function and clinical outcome. We describe the details of an automated, cell
      based, morphometric-based, high-content screen that is used to identify small
      molecules eliciting the differentiation of OPCs after 3 days. Primary screening
      was performed using rat CG-4 cells maintained in culture conditions that normally
      support a progenitor cell-like state. From a library of 73,000 diverse small
      molecules within the Sanofi collection, 342 compounds were identified that
      increased OPC morphological complexity as an indicator of oligodendrocyte
      maturation. Subsequent to the primary high-content screen, a suite of cellular
      assays was established that identified 22 nontoxic compounds that selectively
      stimulated primary rat OPCs but not C2C12 muscle cell differentiation. This
      rigorous triaging yielded several chemical series for further expansion and bio-
      or cheminformatics studies, and their compelling biological activity merits
      further investigation. 

PMID- 25394730
TI  - Tetracycline-based system for controlled inducible expression of group III
      metabotropic glutamate receptors.
AB  - A stable and inducible expression of metabotropic glutamate receptor type 4, 7,
      and 8 was obtained in T-REx 293 cells using the tetracycline system. Tetracycline
      administration to the cell medium resulted in rapid induction and time-dependent
      expression of mGlu receptors, which also correlates with its functionality in a
      cAMP accumulation assay. The pharmacological properties of recombinant mGlu
      receptors were verified using orthosteric and allosteric ligands. Data suggest
      that the Tet-on inducible system is suitable for functional mGlu receptors'
      expression and characterization by means of the cAMP accumulation assay. It makes
      this system a precise, reproducible, and large-scale screening method, as well as
      a reasonable tool to study signaling properties of mGlu receptors. 

PMID- 25394731
TI  - JBS: advancing the science of drug discovery for 20 years!

PMID- 25394732
TI  - Patient perspectives on peer mentoring: type 1 diabetes management in adolescents
      and young adults.
AB  - PURPOSE: The purpose of the study was to identify attitudes and topics relevant
      to peer mentoring as an adherence-promoting intervention for adolescents and
      young adults (YAs) with type 1 diabetes (T1D). METHODS: Self-administered survey
      data were collected in 2 diabetes clinics from a convenience sample of
      adolescents as prospective mentees (ages 13-18) and YAs as prospective mentors
      (ages 19-25) with T1D. Survey topics included demographics, disease history,
      glycemic control, adherence, depression, barriers to disease management, social
      support, and interest in peer mentoring. Descriptive statistical analyses,
      thematic coding, and stepwise multivariate logistic regression were performed.
      RESULTS: A majority of the 54 adolescents and 46 YAs expressed interest in a peer
      mentoring program. Having supportive friends and living in a large household
      positively predicted adolescent interest in having a peer mentor. Approximately
      one-third of all participants experienced social barriers to diabetes management.
      For adolescents, barriers included inflexible schedules, unfamiliar foods, and
      the embarrassment of checking blood glucose in front of others. Young adults
      reported barriers in tracking food consumption and remembering to check blood
      glucose. Various diabetes management skills were in high demand by adolescents,
      who especially desired to learn about managing T1D on their own and in college.
      Participants were open to multiple communication modes, including in-person
      meetings, phone, text messaging, and social media. CONCLUSIONS: Many adolescents
      and young adults with T1D are interested in peer mentoring as a way to facilitate
      learning and sharing essential diabetes management skills and experiences.

PMID- 25394733
TI  - Mortality from thoracic aortic diseases and associations with cardiovascular risk
      factors.
AB  - BACKGROUND: Temporal trends in mortality from thoracic aortic disease are
      unclear. This study examined trends in mortality from thoracic aortic aneurysm
      (TAA) and aortic dissection (AD) with the aim of identifying associations with
      trends in established cardiovascular risk factors. METHODS AND RESULTS: TAA and
      AD mortality (1994-2010) using International Classification of Diseases codes was
      extracted from the World Health Organization mortality database and age
      standardized. World Health Organization InfoBase and International Mortality and
      Smoking Statistics provided risk factor data. Eighteen World Health Organization
      member states were included (Europe=13, Australasia=2, North America=2, Asia=1).
      Ecological regression was performed of temporal trends in cardiovascular risk
      factors (1946-2010) and independent correlations to mortality trends. TAA and AD
      mortality trends show substantial heterogeneity but are generally declining. TAA
      mortality has increased in Hungary, Romania, Japan, and Denmark, and AD mortality
      has increased in Romania and Japan; therefore, the mortality decline is not
      universal. A linear relationship exists between trends in systolic blood
      pressure, cholesterol, and body mass index and mortality from TAA. Body mass
      index demonstrated a negative linear association with female AD mortality,
      whereas trends in systolic blood pressure demonstrated a positive linear
      relationship with male AD mortality. Trends in smoking prevalence were not
      associated with TAA or AD mortality trends. CONCLUSIONS: This population-level
      ecological regression provides evidence that mortality secondary to TAA and
      mortality secondary to AD are both in decline. Differences between countries
      could be explained by population-level changes in common cardiovascular risk
      factors. Public health measures could further reduce mortality from TAA and AD.

PMID- 25394734
TI  - Trends in thoracic aortic aneurysms and dissection: out of the shadows and into
      the light.

PMID- 25394735
TI  - Effects of mild induced hypothermia on hippocampal connexin 43 and glutamate
      transporter 1 expression following traumatic brain injury in rats.
AB  - Traumatic brain injury (TBI) is a common cause of worldwide disability and
      mortality. Currently, the incidence and prevalence of TBI is markedly increasing
      and an effective therapy is lacking. Therapeutic hypothermia (32-35C) has been
      reported to reduce intracranial pressure and induce putative neuroprotective
      effects. However, the underlying molecular mechanisms remain to be elucidated.
      The aim of the present study was to investigate the effects of mild induced
      hypothermia (MIH) on the expression of connexin 43 (Cx43) and glutamate
      transporter 1 (GLT-1) in the hippocampus following TBI in rats. A rat model of
      TBI was created using a modified weight-drop device, followed by 4 h of
      hypothermia (33C) or normothermia (37C). A wet-dry weight method was used to
      assess brain edema and spatial learning ability was evaluated using a Morris
      water maze. The levels of Cx43 and GLT-1 were detected by immunohistochemical and
      western blot analysis, respectively. The results demonstrated that MIH treatment
      improved TBI-induced brain edema and neurological function deficits. In addition,
      therapeutic MIH significantly downregulated Cx43 expression and upregulated the
      levels of GLT-1 in the hippocampus post-TBI. These findings suggested that
      treatment with MIH may provide a novel neuroprotective therapeutic strategy for
      TBI through reversing the increase in Cx43 protein and the decrease in GLT-1.

PMID- 25394736
TI  - Myeloproliferative neoplasms and recurrent thrombotic events in patients
      undergoing liver transplantation for Budd-Chiari syndrome: a single-center
      experience.
AB  - BACKGROUND: Budd-Chiari syndrome is a heterogeneous disease. The role of liver
      transplantation as a treatment option has been discussed since 1976. Many cases
      are related to underlying myeloproliferative neoplasms associated with
      prothrombotic propensity. The aim of this study was to evaluate the long-term
      clinical outcome after liver transplantation for Budd-Chiari syndrome at our
      center, with special emphasis on recurrent thrombosis and underlying
      myeloproliferative disorders. MATERIAL/METHODS: A medical records search revealed
      25 patients transplanted at our center for Budd-Chiari syndrome between 2000 and
      2009. Indications for transplantation were complications of end-stage liver
      disease or acute liver failure. RESULTS: Ten patients were men (40.0%). Median
      age of recipients at transplantation was 29.0 (17-51) years. Eighteen patients
      (72%) had evidence of myeloproliferation, 1 had paroxysmal nocturnal
      hemoglobinuria, and 6 had idiopathic disease. In 55.5% of cases eventually
      diagnosed with myeloproliferative neoplasms, Budd-Chiari syndrome was their
      initial presentation. All patients were maintained on long-term post-transplant
      anticoagulation protocol. The median follow-up time was 58.8 months. Four
      patients (16%) died during follow-up. Acute graft rejection occurred in 16% of
      cases. During the observation period, 5 patients had recurrent thrombotic events.
      The 5-year patient and graft survival rate was 84%. No case of transformation to
      acute leukemia was seen. CONCLUSIONS: Our data show satisfactory long-term
      survival of patients and grafts in the study group. Occult course of
      myeloproliferative neoplasms is frequent in this population and exceeds 50%. We
      observed recurrent thrombosis in 20% of recipients.

PMID- 25394738
TI  - Fluorination of isotopically labeled turbostratic and Bernal stacked bilayer
      graphene.
AB  - Fluorination of graphene opens up a bandgap, which creates opportunities for
      optoelectronics, and also paves the way for the creation of extremely thin
      insulating layers, which can be important for applications in devices. However,
      in spite of many interesting features offered by, for example, unequally doped
      layers in multilayered systems, most of the work has concerned the fluorination
      of graphene monolayers. Here, the fluorination process of graphene bilayers is
      investigated through high-resolution Raman mapping followed by analysis of more
      than 10,000 spectra of bilayer graphene. Isotopically labeled bilayers are used,
      allowing each individual layer in bilayer graphene to be addressed unambiguously.
      The fluorinated graphene is prepared through exposure to XeF2. Monolayer graphene
      is found to be significantly more sensitive to fluorination than bilayer
      graphene. Through comparison of the D/G area ratio and the position of the G band
      for turbostratic and Bernal stacked (AB) bilayers, it is found that the
      fluorination process is more effective for turbostratic than for AB-stacked
      bilayer graphene. The fluorination changes the electronic structure similarly for
      the top and bottom layers in turbostratic bilayers. However, the top layer is
      more sensitive than the bottom layer in AB-stacked bilayers.

PMID- 25394737
TI  - Photoperiod is associated with hippocampal volume in a large community sample.
AB  - Although animal research has demonstrated seasonal changes in hippocampal volume,
      reflecting seasonal neuroplasticity, seasonal differences in human hippocampal
      volume have yet to be documented. Hippocampal volume has also been linked to
      depressed mood, a seasonally varying phenotype. Therefore, we hypothesized that
      seasonal differences in day-length (i.e., photoperiod) would predict differences
      in hippocampal volume, and that this association would be linked to low mood.
      Healthy participants aged 30-54 (M=43; SD=7.32) from the University of Pittsburgh
      Adult Health and Behavior II project (n=404; 53% female) were scanned in a 3T MRI
      scanner. Hippocampal volumes were determined using an automated segmentation
      algorithm using FreeSurfer. A mediation model tested whether hippocampal volume
      mediated the relationship between photoperiod and mood. Secondary analyses
      included seasonally fluctuating variables (i.e., sleep and physical activity)
      which have been shown to influence hippocampal volume. Shorter photoperiods were
      significantly associated with higher BDI scores (R(2)=0.01, beta=-0.12, P=0.02)
      and smaller hippocampal volumes (R(2)=0.40, beta=0.08, P=0.04). However, due to
      the lack of an association between hippocampal volume and Beck Depression
      Inventory scores in the current sample, the mediation hypothesis was not
      supported. This study is the first to demonstrate an association between season
      and hippocampal volume. These data offer preliminary evidence that human
      hippocampal plasticity could be associated with photoperiod and indicates a need
      for longitudinal studies.

PMID- 25394739
TI  - Effectiveness of switching to the rivastigmine transdermal patch from oral
      cholinesterase inhibitors: a naturalistic prospective study in Alzheimer's
      disease.
AB  - Oral donepezil and rivastigmine are two commonly used cholinesterase inhibitors
      (ChEIs) used in Alzheimer's disease (AD). The rivastigmine transdermal patch
      formulation has high tolerability profile, allowing patients to achieve optimal
      therapeutic doses and providing potential advantages over oral ChEIs. This is a 6
      month, multicentre, observational efficacy and tolerability study of switching
      from oral ChEIs to rivastigmine patch in AD patients who failed to show benefit
      from previous treatment. The reasons of the switch were: (1) lack/loss of benefit
      from previous oral ChEI treatment; (2) tolerability problems. The primary outcome
      was cognitive changes measured with the mini-mental state examination (MMSE)
      test. Secondary outcomes were modifications of functional independence and
      behavioral disturbances and occurrence of adverse events (AEs) after switching.
      174 patients, over 180 patients screened, entered the study (lack/loss of
      efficacy: 57 %, tolerability problems: 33 %, both reasons: 10 %). 6 months after
      switching 56 % of patients stabilized or increased the MMSE score respect to
      baseline. The only predictor of this outcome was the response at 3 months. In the
      group with lack/loss of response to oral ChEI, the decline of the MMSE score
      changed from -3.4 +/- 2.5 points in the 6 months before switching to -0.5 +/- 3.2
      in the 6 months after the switch (p < 0.001). There were no significant changes
      in the IADL or NPI scores. Drug discontinuation rate was 20 %, due to AEs (18 %)
      and lack of compliance (2 %). Switching from an unsuccessful oral ChEI therapy to
      rivastigmine patch is effective and safe in more than half of the switched
      patients after a 6-month period.

PMID- 25394740
TI  - Periodical assessment of electrophysiological recovery following sciatic nerve
      crush via surface stimulation in rats.
AB  - When evaluating peripheral nerve regeneration, electrophysiological test is
      recognized as an optimal assessment, which is a quantitative, objective, and
      direct evidence reflecting function as compared to morphological examinations. In
      murine models of nerve regeneration, however, it remains a challenge to record
      compound muscle action potentials (CMAPs) periodically and non-invasively, i.e.,
      with no insult to the nerve. In the present study, we recorded CMAPs in the
      gastrocnemius muscle weekly until 8 weeks after sciatic nerve crush by
      stimulating the nerve in a surface manner, and the electric stimuli were
      delivered to the skin between ischial tuberosity and major trochanter using
      bipolar hook electrodes. The CMAPs were reproducibly recorded in this way from 3
      weeks post-injury, and both amplitude and latency were well correlated to post
      operative time. Furthermore, a strong positive correlation was observed between
      CMAP amplitude and sciatic function index (SFI), a well-recognized assessment for
      sciatic nerve function. CMAP recordings by direct nerve stimulation at 8 weeks
      post-injury showed no significant difference in amplitude compared to surface
      stimulation, but the peak latency was relatively longer than the latter. This
      study indicated that non-invasive surface stimulation-based periodical recording
      of CMAPs was a practical electrophysiological approach to monitor the progression
      of peripheral nerve regeneration in murine models.

PMID- 25394741
TI  - Bilateral subthalamic stimulation for advanced Parkinson disease: early
      experience at an Eastern center.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can improve the
      life quality of patients with advanced Parkinson disease (PD). However, previous
      studies have stemmed mainly from Western centers. Present study analyzed the 6
      month outcomes of bilateral STN-DBS therapy that were observed during a 9-year
      period at a Taiwanese institute. We retrospectively reviewed 72 consecutive
      patients, whose mean disease history was 8 years when they underwent surgery. The
      median "drug-off" Hoehn and Yahr stage was 3. The STN was targeted using T2
      weighted magnetic resonance imaging and electrophysiological guidance. The over
      time mean differences in the Unified PD Rating Scale (UPDRS) scores and daily
      levodopa-equivalent dose (LED) were assessed using the repeated measurements
      ANOVA at 3 and 6 months relative to those of presurgical drug-off baseline. At 6
      months postsurgery, the mean UPDRS total, Part II and Part III subscores
      significantly decreased by 27, 30 and 25 %, respectively, with clinically high
      effect size. Tremors were markedly (66 %) ameliorated. Moreover, problems of
      akinesia, rigidity, and locomotion were significantly improved by 20 %. The mean
      daily LED needs decreased by 25 %; thus, drug-induced dyskinesia was markedly (80
      %) diminished. STN-DBS therapy could provide similarly effective impacts to
      Eastern and Western PD patients. Preoperative optimal selection of patients and
      postoperative delicate programming ensure a better surgical improvement.

PMID- 25394742
TI  - Isolating cells from female/male blood mixtures using florescence in situ
      hybridization combined with low volume PCR and its application in forensic
      science.
AB  - To obtain single-source short tandem repeat (STR) profiles in trace female/male
      blood mixture samples, we combined florescence in situ hybridization (FISH),
      laser microdissection, and low volume PCR (LV-PCR) to isolate male/female cells
      and improve sensitivity. The results showed that isolation of as few as 10
      leukocytes was sufficient to yield full STR profiles in fresh female or male
      blood samples for 32 independent tests with a low additional alleles rate (3.91%)
      and drop-out alleles rate (5.01%). Moreover, this procedure was tested in two
      fresh blood mixture series at three ratios (1:5, 1:10, and 1:20), two mock
      female/male blood mixture casework samples, and one practical casework sample.
      Male and female STR profiles were successfully detected in all of these samples,
      showing that this procedure could be used in forensic casework in the future.

PMID- 25394743
TI  - Length heteroplasmy of the polyC-polyT-polyC stretch in the dog mtDNA control
      region.
AB  - Previously, the mitochondrial control region of 214 Belgian dogs was sequenced.
      Analysis of this data indicated length heteroplasmy of the polyT stretch in the
      polyC-polyT-polyC stretch from positions 16661 to 16674. Nine polyC-polyT-polyC
      haplotype combinations were observed, consisting of seven major haplotypes
      (highest signal intensity) combined with minor haplotypes (lower signal
      intensity) one T shorter than the major haplotype in all but three dogs. The
      longer the polyT stretch, the smaller was the difference in signal intensity
      between the major and minor haplotype peaks. Additional sequencing, cloning, and
      PCR trap experiments were performed to further study the intra-individual
      variation of this mitochondrial DNA (mtDNA) region. Cloning experiments
      demonstrated that the proportion of clones displaying the minor haplotypes also
      increased with the length of the polyT stretch. Clone amplification showed that
      in vitro polymerase errors might contribute to the length heteroplasmy of polyT
      stretches with at least 10 Ts. Although major and minor polyC-polyT-polyC
      haplotypes did not differ intra-individually within and between tissues in this
      study, interpretation of polyT stretch variation should be handled with care in
      forensic casework. 

PMID- 25394744
TI  - Assets and pitfalls of chemical and microscopic analyses on gunshot residues in
      skeletonized bodies: a report of five cases.
AB  - In case of gunshot wounds, forensic anthropologists and pathologists have many
      tools at hand, and the assistance that chemical and microscopic investigations
      can provide in such scenarios is often valuable and crucial. However, the results
      of such analyses in the search of gunshot residues (GSR) ought not to be
      acritically considered. We report five cases where chemical (sodium rhodizonate)
      and microscopic (scanning electron microscopy-energy dispersive X-ray
      spectroscopy (SEM-EDX)) analyses were performed for the search of GSR. Four cases
      concerned the forensic field and analyses on buried, charred, or submerged
      remains, whereas one case concerned the historical remains of a soldier of the
      First World War. In every case, the search for GSR with these techniques showed
      their persistence even after long periods and preservation in peculiar
      environments. However, chemical analyses provided their contribution, but in two
      cases, anthropological analyses provided crucial and solving results. The five
      cases show the indisputable usefulness of chemical and microscopic analyses in
      the search of GSR in gunshot wounds and especially how such residues may survive
      in time and in adverse environmental conditions. However, experts should always
      be dubious about some pitfalls (such as contamination) one can frequently find in
      these scenarios. 

PMID- 25394745
TI  - Sexual dimorphism in cranial morphology among modern South Africans.
AB  - Pattern expressions of morphoscopic cranial traits vary across populations with
      classification accuracies being highly dependent on the reference collection to
      which unknown skulls are compared. Despite recent developments in population
      specific standards for South Africans, researchers have not addressed the
      accuracy of morphological methods. Several studies demonstrate differences in
      sexual dimorphism between South Africans and North Americans, warranting a need
      to re-evaluate sex estimation methods in South Africa. The purposes of this study
      were to test the reliability and accuracy of the Walker (2008) method and to
      examine patterns of sexual dimorphism among South Africans. A total of 245 modern
      Black and White South African male and female crania from the Pretoria Bone
      Collection, University of Pretoria, were scored using the Walker (2008)
      methodology. Cohen's kappa was used to evaluate reliability of the method, and
      percent correct assessed validity of the method. Logistic regression was utilised
      to create modified population-specific formulae. Inter- and intra-observer
      agreement was moderate to excellent (0.60-0.90), except for the mental eminence
      (0.40). The percent correct results for sex were 80% or higher for combinations
      of glabella, mastoid and menton and between 68% and 73% for menton, mastoid,
      orbital and nuchal margin using logistic equations of Walker (2008). White males
      had the highest (94-97%) and White females had the lowest (31-62%) percent
      correct. The low accuracies obtained when using Walker's (2008) equations
      emphasised the need for population-specific sex estimation models. Modified
      formulae for South Africans were created, yielding higher classification rates
      (84-93%) than when North American standards were employed.

PMID- 25394746
TI  - Accuracies of facial soft tissue depth means for estimating ground truth skin
      surfaces in forensic craniofacial identification.
AB  - Facial soft tissue thickness means have long been used as a proxy to estimate the
      soft tissue envelope, over the skull, in craniofacial identification. However,
      estimation errors of these statistics are not well understood, making casework
      selection of the best performing estimation models impossible and overarching
      method accuracies controversial. To redress this situation, residuals between
      predicted and ground truth values were calculated in two experiments: (1) for 27
      suites of means drawn from 10 recently published studies, all examining the same
      10 landmarks (N >= 3051), and tested against six independent raw datasets of
      contemporary living adults (N = 797); and (2) pairwise tests of the above six,
      and five other, raw datasets (N = 1063). In total, 380 out-of-sample tests of 416
      arithmetic means were conducted across 11 independent samples. Experiment 1
      produced an overarching mean absolute percentage error (MAE) of 29% and a
      standard error of the estimate (S(est)) of 2.7 mm. Experiment 2 yielded MAE of
      32% and S(est) of 2.8 mm. In any instance, MAE was always >=20% of the ground
      truth value. The overarching 95% limits of the error, for contemporary samples,
      was large (11.4 mm). CT-derived means from South Korean males and Black South
      African females routinely performed well across the test samples and produced the
      smallest errors of any tests (but did so for Black American male reference
      samples). Sample-specific statistics thereby performed poorly despite discipline
      esteem. These results-and the practice of publishing means without prior model
      validation-demand major reforms in the field.

PMID- 25394747
TI  - Airway responses towards allergens - from the airway epithelium to T cells.
AB  - The prevalence of allergic diseases such as allergic rhinitis is increasing,
      affecting up to 30% of the human population worldwide. Allergic sensitization
      arises from complex interactions between environmental exposures and genetic
      susceptibility, resulting in inflammatory T helper 2 (Th2) cell-derived immune
      responses towards environmental allergens. Emerging evidence now suggests that an
      epithelial dysfunction, coupled with inherent properties of environmental
      allergens, can be responsible for the inflammatory responses towards allergens.
      Several epithelial-derived cytokines, such as thymic stromal lymphopoietin
      (TSLP), IL-25 and IL-33, influence tissue-resident dendritic cells (DCs) as well
      as Th2 effector cells. Exposure to environmental allergens does not elicit Th2
      inflammatory responses or any clinical symptoms in nonatopic individuals, and
      recent findings suggest that a nondamaged, healthy epithelium lowers the DCs'
      ability to induce inflammatory T-cell responses towards allergens. The purpose of
      this review was to summarize the current knowledge on which signals from the
      airway epithelium, from first contact with inhaled allergens all the way to the
      ensuing Th2-cell responses, influence the pathology of allergic diseases. 

PMID- 25394748
TI  - Perinatal transmission of dengue: a case report.
AB  - BACKGROUND: Dengue in pregnancy is associated with many maternal and foetal
      outcomes including perinatal transmission of dengue infection. CASE PRESENTATION:
      A baby was born by emergency caesarean section due to foetal distress and
      meconium stained liquor, to a 27-year old primi-gravidae, Sinhalese female, who
      was febrile during and 2 days prior to labour. The baby had evidence of
      respiratory distress due to meconium aspiration and was cared for in the special
      care baby unit for 3 days. On the 4th day he developed fever and serial blood
      counts showed a gradual rise in the haematocrit (>20% of baseline value) and
      lowering of platelet counts. The baby was treated for sepsis and as Sri Lanka was
      experiencing a massive dengue epidemic was also tested for dengue. His dengue NS1
      antigen test was strongly positive and the dengue IgM antibodies weakly positive
      on day 3 of illness. The mother was positive for both dengue IgM and IgG
      antibodies. CONCLUSION: Although rare, vertical transmission of the dengue virus
      has been reported and the baby most likely developed dengue due to perinatal
      transmission of dengue.

PMID- 25394749
TI  - Of mice and the 'Age of Discovery': the complex history of colonization of the
      Azorean archipelago by the house mouse (Mus musculus) as revealed by
      mitochondrial DNA variation.
AB  - Humans have introduced many species onto remote oceanic islands. The house mouse
      (Mus musculus) is a human commensal and has consequently been transported to
      oceanic islands around the globe as an accidental stowaway. The history of these
      introductions can tell us not only about the mice themselves but also about the
      people that transported them. Following a phylogeographic approach, we used
      mitochondrial D-loop sequence variation (within an 849- to 864-bp fragment) to
      study house mouse colonization of the Azores. A total of 239 sequences were
      obtained from all nine islands, and interpretation was helped by previously
      published Iberian sequences and 66 newly generated Spanish sequences. A Bayesian
      analysis revealed presence in the Azores of most of the D-loop clades previously
      described in the domesticus subspecies of the house mouse, suggesting a complex
      colonization history of the archipelago as a whole from multiple geographical
      origins, but much less heterogeneity (often single colonization?) within islands.
      The expected historical link with mainland Portugal was reflected in the pattern
      of D-loop variation of some of the islands but not all. A more unexpected
      association with a distant North European source area was also detected in three
      islands, possibly reflecting human contact with the Azores prior to the 15th
      century discovery by Portuguese mariners. Widening the scope to colonization of
      the Macaronesian islands as a whole, human linkages between the Azores, Madeira,
      the Canaries, Portugal and Spain were revealed through the sharing of mouse
      sequences between these areas. From these and other data, we suggest mouse
      studies may help resolve historical uncertainties relating to the 'Age of
      Discovery'. 

PMID- 25394750
TI  - Perceptions of treatment adherence among people with mental health problems and
      health care professionals.
AB  - AIMS: To explore patients' and mental healthcare professionals' perceptions of
      supportive and restrictive indicators of adherence to treatment in patients with
      mental health problems. BACKGROUND: People with mental health problems may have
      difficulties adhering to their treatment, causing relapses and hospitalizations.
      It is, therefore, important to learn more about how patients' treatment adherence
      can be supported and what jeopardizes adherence. DESIGN: A descriptive
      qualitative study. METHODS: Nine focus groups and semi-structured interviews were
      conducted in Finland during 2010-2011. The patients (n = 19) were recruited from
      patient associations and the healthcare professionals (n = 42) from healthcare
      organizations. The data were analysed using inductive content analysis. FINDINGS:
      Participants agreed that treatment adherence can be supported. Suggestions
      focused on treatment planning mindful of both patient involvement and needs. A
      structured daily routine helps patients manage their everyday issues and further
      facilitates adherence. On the other hand, patients found that their adherence was
      affected by factors related to the mental health system, including arrangements
      for follow-up care, access to services, the receptiveness of providers to meet
      patient needs and a disconnect time between hospital and community life.
      CONCLUSION: Patient adherence should already be taken into account when treatment
      is planned. The content of treatment should be individually designed according to
      the patient's activities of daily life. In addition, stressing the importance of
      medication and listening to the patient's opinions and experiences of taking
      medication may improve the patient's willingness to adhere.

PMID- 25394751
TI  - Building up quarternary stereocenters of chromans by asymmetric redox
      organocatalysis: a new entry to vitamin E.
AB  - High-turnover catalysis offers a novel concept for the efficient chemo- and
      enantioselective preparation of chroman intermediates, which are useful for the
      synthesis of tocopherols (vitamin E components) and other biologically active
      compounds. A chiral ammonium iodide catalyst mediates the cycloetherification in
      combination with a cooxidant and an inorganic base in excellent yield and up to
      93 % ee. OTs=para-toluenesulfonyl. 

PMID- 25394753
TI  - [Epidemiology of multidrug-resistant organisms in travellers: Results of a 2-year
      screening in a German level 1 trauma center].
AB  - INTRODUCTION: Antibiotic resistance has emerged as one of the eminent public
      health concerns. Infections can cause prolonged illness and are related to a high
      mortality. Expanding tourism and global travelling is one risk factor for
      spreading of "superbugs" (multidrug-resistant organisms, MDRO) from endemic
      countries with less hygiene conditions and an overuse of antibiotics. Persons
      that have had contact with foreign healthcare systems are at a high risk of being
      contaminated with these bacteria. Returning home they can transmit them to other
      patients and release nosocomial infections. MATERIAL AND METHODS: To improve the
      prevention of nosocomial infections at the Unfallkrankenhaus Berlin (ukb), at the
      beginning of 2011 the hospital hygiene commission decided to expand the existing
      testing for methicillin-resistant Staphylococcus aureus (MRSA) to screening of
      incoming patients with contact to foreign healthcare systems to identify
      colonization or infection with multidrug-resistant bacteria. RESULTS: In a 24
      month period 155 patients were screened for MDROs, 31 patients (20%) were found
      to be positive, 18 showed colonization,13 patients showed infection and a
      multifold colonization was found in 10 patients. A total of 26 multiresistant
      gram-negative resistant rod-shaped bacilli resistant to 3 of the 4 classes of
      antibiotics (3MRGNs) were detected, 12 cases of 4MRGNs and 9 MRSAs. The average
      isolation time was 39 days and the calculated costs for isolation of MDRO
      positive patients were approximately 205,000 ?. The average case mix index of
      MDRO positive patients was 9.54. CONCLUSION: The high percentage of patients with
      MDROs who had had contact with foreign healthcare systems or stayed in foreign
      countries shows the importance of screening to identify these persons and thus
      help avoid nosocomial infections of other patients as well as to protect
      healthcare workers. No transmissions or nosocomial infections were observed
      during the study period.

PMID- 25394754
TI  - Determination of the myocardial performance index in deteriorating grades of
      intrauterine growth restriction and its link to adverse outcomes.
AB  - AIM: The aim of this study is to determine the fetal modified myocardial
      performance index (Mod-MPI) and E-wave/A-wave peak velocities (E/A ratio) in
      deteriorating grades of intrauterine growth restriction (IUGR) and its link to
      adverse outcomes defined as perinatal death, hypoxic ischemic encephalopathy,
      neonatal resuscitation, neonatal cord pH <7.15, intraventricular hemorrhage and
      bronchopulmonary dysplasia. METHOD: Forty three pregnant women with IUGR defined
      as the abdominal circumference <10th percentile for gestational age and umbilical
      resistance index >2 standard deviations in the third trimester of pregnancy were
      matched for gestational age and maternal age with 43 women with appropriate-for
      gestational-age fetuses. The IUGR group was subdivided on the basis of
      multivessel Doppler anomalies into different grades of growth restriction. Mod
      MPI and E/A ratio were determined and linked to perinatal outcome. RESULTS: The
      median Mod-MPI was significantly higher in growth-restricted fetuses compared
      with controls (0.59 vs 0.37, p < 0.001) and increased with severity of IUGR, the
      classification of which was based on degree of abnormality of the umbilical
      resistance index, presence of arterial redistribution and degree of abnormality
      of the ductus venosus (DV) Doppler indices. A cut-off Mod-MPI value of 0.54
      conferred a sensitivity of 87% [confidence interval (CI): 66-97%], specificity of
      75% (CI: 55-91%) and a likelihood ratio (LR) of 3.47 for an adverse outcome. A
      cut-off Mod-MPI value of 0.67 conferred a sensitivity of 100% (CI: 54-100%),
      specificity of 81% (CI: 65-92%) and LR of 5.28 for perinatal death. No abnormal
      outcomes occurred in controls. In logistic regression analysis, the MPI remained
      a significant predictor of adverse outcome after adjusting for gestational age of
      delivery, fetal weight, E/A ratio, maternal age, DV Doppler indices, amniotic
      fluid index and umbilical artery resistance index [adjusted odds ratio, 95% CI:
      2.60 (1.15-5.83), p-value 0.02]. MPI fared significantly better than the E/A
      ratio as a predictor of adverse outcome (area under the receiver operating
      characteristic curve of 0.94 and 0.76, p < 0.001). CONCLUSION: Fetal myocardial
      performance deteriorates with severity of growth restriction. There is an
      association between severity of the MPI elevation and rates of adverse perinatal
      outcome. The Mod-MPI and E/A ratio have the potential to be integrated into
      routine surveillance techniques of the growth-restricted fetus. (c) 2014 John
      Wiley & Sons, Ltd.

PMID- 25394755
TI  - The Dutch national summit on preconception care: a summary of definitions,
      evidence and recommendations.

PMID- 25394756
TI  - MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and
      proliferation by targeting FASLG.
AB  - To investigate whether miR-21 can affect the apoptosis and proliferation of
      glioblastoma cancer stem cells (GSCs) from down-regulating FASLG. The expression
      of miRNA-21 was detected by quantitative real-time PCR in normal brain tissue and
      glioblastoma samples, and the changes of miRNA-21 expression between GSCs and non
      GSCs were also detected. The apoptosis and proliferation ability of miR-21 in
      GSCs were analyzed by MTT and flow cytometry assay after anti-miR-21
      transfection. For the regulation mechanism analysis of miR-21, TargetScan, PicTar
      and microRNA were selected to predict some potential target genes of miR-21. The
      predicted gene was identified to be the direct and specific target gene of miR-21
      by luciferase activities assay and western blot. RNA interference technology was
      used to confirm the apoptosis and proliferation effects of miR-21 were directly
      induced by FASLG. The expression of miR-21 increased significantly in
      glioblastoma contrast to normal brain tissue, and miR-21 up-regulated in GSCs
      remarkably. The proliferation of GSCs cell could be inhibited with high
      expression of miR-21 and this effect could be restored by miR-21 knocked down.
      Mechanism analysis revealed that FASLG was a specific and direct target gene of
      miR-21. The advanced effects of anti-miR-21 on GSCs apoptosis and proliferation
      were mediated by expression of silenced FASLG. In summary, aberrantly expressed
      miR-21 regulates GSCs apoptosis and proliferation partly through directly down
      regulating FASLG protein expression in GSCs and this might offer a new potential
      therapeutic stratagem for glioblastoma. 

PMID- 25394757
TI  - Cloning and expression of a CYP720B orthologue involved in the biosynthesis of
      diterpene resin acids in Pinus brutia.
AB  - Cytochrome P450 monooxygenases mediate a broad range of oxidative reactions
      involved in the biosynthesis of both primary and secondary metabolites in plants.
      Until now, only two P450 genes, CYP720B1 from Pinus taeda and CYP720B4 from Picea
      sitchensis, have been functionally characterised and described in the literature.
      The purpose of this study was to describe the cloning and expression of CYP720B
      from Pinus brutia due to its suggested role in the synthesis of bioactive
      compounds used for chemical defence against insects. A PCR product of the P.
      brutia CYP720B gene was cloned into the pCR8/GW/TOPO cloning vector. After
      optimising the sequence for codon usage in yeast, it was transferred into the
      inducible expression vector pYES-DEST52 and transfected into the S. cerevisiae
      INVSc1 strain. Sequence analysis showed that the P. brutia CYP720B gene contains
      an open reading frame of 1,464 nucleotides, which encodes a 53,570 Da putative
      protein of 487 amino acid residues. The putative protein contains the classic
      heme-binding sequence motif that is conserved in all P450 enzymes. It shares 99
      and 61% identity with the deduced amino acid sequences of CYP720B1 from Pinus
      taeda and CYP720B4 from Picea sitchensis, respectively. Recombinant CYP720B
      protein expression was confirmed using western blot analysis. Furthermore,
      recombinant CYP720B was functionally active, showing a Soret peak at
      approximately 448 nm in the reduced CO difference spectra. These data suggest
      that the cloned gene is an orthologue of CYP720B in P. brutia and might be
      involved in DRA biosynthesis.

PMID- 25394758
TI  - "Turn-on" fluorescence probe integrated polymer nanoparticles for sensing
      biological thiol molecules.
AB  - A "turn-on" thiol-responsive fluorescence probe was synthesized and integrated
      into polymeric nanoparticles for sensing intracellular thiols. There is a photo
      induced electron transfer process in the off state of the probe, and this process
      is terminated upon the reaction with thiol compounds. Configuration interaction
      singles (CIS) calculation was performed to confirm the mechanism of this process.
      A series of sensing studies were carried out, showing that the probe-integrated
      nanoparticles were highly selective towards biological thiol compounds over non
      thiolated amino acids. Kinetic studies were also performed to investigate the
      relative reaction rate between the probe and the thiolated amino acids.
      Subsequently, the Gibbs free energy of the reactions was explored by means of the
      electrochemical method. Finally, the detection system was employed for sensing
      intracellular thiols in cancer cells, and the sensing selectivity could be
      further enhanced with the use of a cancer cell-targeting ligand in the
      nanoparticles. This development paves a path for the sensing and detection of
      biological thiols, serving as a potential diagnostic tool in the future. 

PMID- 25394760
TI  - Endothelial nanomedicine for the treatment of pulmonary disease.
AB  - INTRODUCTION: Even though pulmonary diseases are among the leading causes of
      morbidity and mortality in the world, exceedingly few life-prolonging therapies
      have been developed for these maladies. Relief may finally come from nanomedicine
      and targeted drug delivery. AREAS COVERED: Here, we focus on four conditions for
      which the pulmonary endothelium plays a pivotal role: acute respiratory distress
      syndrome, primary graft dysfunction occurring immediately after lung
      transplantation, pulmonary arterial hypertension and pulmonary embolism. For each
      of these diseases, we first evaluate the targeted drug delivery approaches that
      have been tested in animals. Then we suggest a 'need specification' for each
      disease: a list of criteria (e.g., macroscale delivery method, stability, etc.)
      that nanomedicine agents must meet in order to warrant human clinical trials and
      investment from industry. EXPERT OPINION: For the diseases profiled here,
      numerous nanomedicine agents have shown promise in animal models. However, to
      maximize the chances of creating products that reach patients, nanomedicine
      engineers and clinicians must work together and use each disease's need
      specification to guide the design of practical and effective nanomedicine agents.

PMID- 25394759
TI  - Association of red blood cell transfusion and in-hospital mortality in patients
      admitted to the intensive care unit: a systematic review and meta-analysis.
AB  - INTRODUCTION: Previous research has debated whether red blood cell (RBC)
      transfusion is associated with decreased or increased mortality in patients
      admitted to the intensive care unit (ICU). We conducted a systematic review and
      meta-analysis to assess the relationship of RBC transfusion with in-hospital
      mortality in ICU patients. METHODS: We carried out a literature search on Medline
      (1950 through May 2013), Web of Science (1986 through May 2013) and Embase (1980
      through May 2013). We included all prospective and retrospective studies on the
      association between RBC transfusion and in-hospital mortality in ICU patients.
      The relative risk for the overall pooled effects was estimated by random effects
      model. Sensitivity analyses were conducted to assess potential bias. RESULTS: The
      meta-analysis included 28,797 participants from 18 studies. The pooled relative
      risk for transfused versus nontransfused ICU patients was 1.431 (95% CI, 1.105 to
      1.854). In sensitivity analyses, the pooled relative risk was 1.211 (95% CI,
      0.975 to 1.505) if excluding studies without adjustment for confounders, 1.178
      (95% CI, 0.937 to 1.481) if excluding studies with relative high risk of bias,
      and 0.901 (95% CI, 0.622 to 1.305) if excluding studies without reporting hazard
      ratio (HR) or relative risk (RR) as an effect size measure. Subgroup analyses
      revealed increased risks in studies enrolling patients from all ICU admissions
      (RR 1.513, 95%CI 1.123 to 2.039), studies without reporting information on
      leukoreduction (RR 1.851, 95%CI 1.229 to 2.786), studies reporting unadjusted
      effect estimates (RR 3.933, 95%CI 2.107 to 7.343), and studies using odds ratio
      as an effect measure (RR 1.465, 95%CI 1.049 to 2.045). Meta-regression analyses
      showed that RBC transfusion could decrease risk of mortality in older patients
      (slope coefficient -0.0417, 95%CI -0.0680 to -0.0154). CONCLUSIONS: There is lack
      of strong evidence to support the notion that ICU patients who receive RBC
      transfusion have an increased risk of in-hospital death. In studies adjusted for
      confounders, we found that RBC transfusion does not increase the risk of in
      hospital mortality in ICU patients. Type of patient, information on
      leukoreduction, statistical method, mean age of patient enrolled and publication
      year of the article may account for the disagreement between previous studies.

PMID- 25394761
TI  - u-Opioid receptor activation by tramadol and O-desmethyltramadol (M1).
AB  - Tramadol has been used as an analgesic for several decades. u-Opioid receptors
      (uORs) are the major receptors that mediate the analgesic effects of opioids.
      Although uORs have been thought to be one of the sites of action of tramadol,
      there has been no report that directly proves whether tramadol is an agonist of
      MUOR or not. In this study, we examined the effects of tramadol and its main
      active metabolite O-desmethyltramadol (M1), on the function of uORs using Xenopus
      oocytes expressing cloned human uORs. The effects of tramadol and M1 were
      evaluated using the Ca(2+)-activated Cl(-) current assay method for G(i/o)
      protein-coupled receptors by using a uOR fused to G(qi5) (uOR-G(qi5)) in Xenopus
      oocytes. DAMGO [(D-Ala(2), N-MePhe(4), Gly(5)-ol)-enkephalin] evoked Cl(-)
      currents in oocytes expressing uOR-G(qi5) in a concentration-dependent manner.
      Tramadol and M1 also evoked Cl(-) currents in the oocytes expressing uOR-G(qi5);
      however, relatively higher concentrations (compared to DMAGO) were necessary to
      induce such currents. Tramadol and M1 had a direct effect on uORs expressed in
      Xenopus oocytes. Although the monoamine uptake system and several types of ligand
      gated ion channels are thought to be one of the targets for tramadol, tramadol
      induced antinociception may be mediated at least in part, by the direct
      activation of uORs.

PMID- 25394765
TI  - Andreas Radbruch: winner of the Avery-Landsteiner Prize for Immunology 2014.

PMID- 25394762
TI  - A randomized controlled trial of the effect of preoperative dexmedetomidine on
      the half maximal effective concentration of propofol for successful i-gel
      insertion without muscle relaxants.
AB  - BACKGROUND: Dexmedetomidine is a useful anesthetic adjuvant for general
      anesthesia. We determined whether preoperative dexmedetomidine administration
      could reduce the half maximal effective concentration (EC50) of propofol for
      successful i-gel insertion without muscle relaxants. METHODS: Thirty-seven
      patients were randomly allocated to one of two groups. In the dexmedetomidine
      group (n = 19), dexmedetomidine (1 ug/kg) was loaded for 10 min preoperatively.
      In the control group (n = 20), the same volume of 0.9% normal saline was
      administered in the same manner. The EC50 of propofol for successful i-gel
      insertion was determined using Dixon's up-and-down method. The EC50 of propofol
      was calculated as the midpoint concentration after at least six crossover points
      had been obtained. For successful i-gel insertion, all of the following four
      factors were required-(1) no major movement of the body within 1 min of
      insertion, (2) no significant resistance to mouth opening, (3) cough <=2, and (4)
      visible square wave capnogram without air leakage at a peak airway pressure of
      <10 cmH2O. Mean blood pressure (MBP) and heart rate (HR) were monitored during
      the peri-insertion period of i-gel. RESULTS: The EC50 of propofol for successful
      i-gel insertion was 3.18 MUg/mL in the dexmedetomidine group and 6.75 MUg/mL in
      the control group (p < 0.001). The incidence of hypotension (MBP <80% of the
      baseline) during the peri-insertion period of i-gel was higher in the control
      group (p = 0.001), whereas the incidence of bradycardia (HR <80% of the baseline)
      was higher in the dexmedetomidine group (p = 0.001). CONCLUSIONS: Preoperative
      dexmedetomidine reduced the EC50 of propofol for successful i-gel insertion
      without muscle relaxants.

PMID- 25394769
TI  - Delineating optimal settlement areas of juvenile reef fish in Ngederrak Reef,
      Koror state, Republic of Palau.
AB  - Establishing the effectiveness of habitat features to act as surrogate measures
      of diversity and abundance of juvenile reef fish provides information that is
      critical to coral reef management. When accurately set on a broader spatial
      context, microhabitat information becomes more meaningful and its management
      application becomes more explicit. The goal of the study is to identify coral
      reef areas potentially important to juvenile fishes in Ngederrak Reef, Republic
      of Palau, across different spatial scales. To achieve this, the study requires
      the accomplishment of the following tasks: (1) structurally differentiate the
      general microhabitat types using acoustics; (2) quantify microhabitat association
      with juvenile reef fish community structure; and (3) conduct spatial analysis of
      the reef-wide data and locate areas optimal for juvenile reef fish settlement.
      The results strongly suggest the importance of branching structures in
      determining species count and abundance of juvenile reef fish at the outer reef
      slope of Ngederrak Reef. In the acoustic map, the accurate delineation of these
      features allowed us to identify reef areas with the highest potential to harbor a
      rich aggregation of juvenile reef fish. Using a developed spatial analysis tool
      that ranks pixel groups based on user-defined parameters, the reef area near the
      Western channel of Ngederrak is predicted to have the most robust aggregation of
      juvenile reef fish. The results have important implications not only in
      management, but also in modeling the impacts of habitat loss on reef fish
      community. At least for Ngederrak Reef, the results advanced the utility of
      acoustic systems in predicting spatial distribution of juvenile fish. 

PMID- 25394770
TI  - Baseline assessment of heavy metal concentrations in surficial sediment from
      Kachemak Bay, Alaska.
AB  - Heavy metal inputs to coastal Alaska ecosystems are driven by sediment loads from
      glacial meltwater and river outflows. This study characterized the spatial
      distribution of 16 major and trace metals in five strata in Kachemak Bay, as well
      as sediment total organic carbon content and grain size. Homer Harbor, a shallow
      harbor within the study area, contained elevated metal concentrations compared to
      the other strata. Outside the harbor, several metals, including Cr, Ni, Pb, and
      Zn, were significantly higher in the eastern strata than in the western portions
      of the bay. The opposite was true for a few other metals, such as Hg. However,
      most metal concentrations were below the National Oceanic and Atmospheric
      Administration's sediment quality guidelines for sediment toxicity to benthic
      communities. 

PMID- 25394771
TI  - Natural peste des petits ruminants virus infection in Black Bengal goats:
      virological, pathological and immunohistochemical investigation.
AB  - BACKGROUND: Peste des Petits Ruminants (PPR), also known as Goat Plague, occurs
      in goats, sheep and related species. It is caused by a morbillivirus in the
      family Paramyxoviridae. In Bangladesh PPR is endemic and it causes serious
      economic losses. Pathology of PPR has been reported in different goat and sheep
      breeds from natural and experimental infections. Field results are better
      indicators of pathogenicity of the circulating virus. The severity of the disease
      varies with species, breed and immune status of the host. Pathological
      investigations of natural outbreaks of PPR in Balck Bengal goats are very
      limited. The current investigation was aimed at describing pathology and antigen
      localization in natural PPR infections in Black Bengal goats. RESULTS: A total of
      28 outbreaks were investigated clinically and virologically. Average flock
      morbidity and mortality were 75% and 59%, respectively, with case fatality rate
      of 74%. Necropsy was conducted on 21 goats from 15 outbreaks. The major gross
      lesions were congestion of gastrointestinal tract, pneumonia, engorged spleen,
      and oedematous lymphnodes. Histopathological examination revealed severe
      enteritis with denudation of intestinal epithelium, severe broncho-interstitial
      pneumonia with macrophages within lung alveoli and extensive haemorrhages with
      depletion of lymphoid cells and infiltration of macrophages in the sinuses of
      spleen. In lymph nodes, the cortical nodules were replaced by wide sinusoids with
      severe depletion of lymphocytes, infiltration of mononuclear cells and some giant
      cells in sub-capsular areas and medullary sinuses. PPR virus antigen was found in
      pneumocytes and alveolar macrophages in lungs. Viral RNA could be detected by RT
      PCR in 69 out of 84 nasal swab, 59 out of 84 blood and 21 out of 21 lymph node
      samples. Sequence analyses revealed closeness of Bangladeshi strains with other
      recent Asian isolates. CONCLUSION: Natural outbreaks of PPR in Black Bengal goats
      in Bangladesh resulted in 75% and 59% flock morbidity and mortality,
      respectively, with a case fatality rate of 74%. The striking histo-morphologic
      diagnosis of PPR was acute pneumonia and severe gastro-enteritis. A detailed
      experimental pathological study on Black Bengal goats infected with recent
      isolates is required.

PMID- 25394772
TI  - Transgenic fish systems and their application in ecotoxicology.
AB  - The use of transgenics in fish is a relatively recent development for advancing
      understanding of genetic mechanisms and developmental processes, improving
      aquaculture, and for pharmaceutical discovery. Transgenic fish have also been
      applied in ecotoxicology where they have the potential to provide more advanced
      and integrated systems for assessing health impacts of chemicals. The zebrafish
      (Daniorerio) is the most popular fish for transgenic models, for reasons
      including their high fecundity, transparency of their embryos, rapid
      organogenesis and availability of extensive genetic resources. The most commonly
      used technique for producing transgenic zebrafish is via microinjection of
      transgenes into fertilized eggs. Transposon and meganuclease have become the most
      reliable methods for insertion of the genetic construct in the production of
      stable transgenic fish lines. The GAL4-UAS system, where GAL4 is placed under the
      control of a desired promoter and UAS is fused with a fluorescent marker, has
      greatly enhanced model development for studies in ecotoxicology. Transgenic fish
      have been developed to study for the effects of heavy metal toxicity (via heat
      shock protein genes), oxidative stress (via an electrophile-responsive element),
      for various organic chemicals acting through the aryl hydrocarbon receptor,
      thyroid and glucocorticoid response pathways, and estrogenicity. These models
      vary in their sensitivity with only very few able to detect responses for
      environmentally relevant exposures. Nevertheless, the potential of these systems
      for analyses of chemical effects in real time and across multiple targets in
      intact organisms is considerable. Here we illustrate the techniques used for
      generating transgenic zebrafish and assess progress in the development and
      application of transgenic fish (principally zebrafish) for studies in
      environmental toxicology. We further provide a viewpoint on future development
      opportunities.

PMID- 25394773
TI  - Pancreas transplantation with enteroanastomosis to native duodenum poses
      technical challenges--but offers improved endoscopic access for scheduled
      biopsies and therapeutic interventions.
AB  - To facilitate endoscopic access for rejection surveillance and stenting of the
      pancreas, we have abandoned the duodenojejunostomy (DJ) in favor of
      duodenoduodenostomy (DD) in pancreas transplantation (PTx). From September 2012
      to September 2013 we performed 40 PTx with DD; 20 solitary-PTx (S-PTx) and 20
      simultaneous pancreas and kidney transplantation (SPK). We compared the outcomes
      with results from 40 PTx-DJ (10 S-PTx and 30 SPK) from the preceding era. The DD
      enteroanastomoses were performed successfully. Endoscopic pancreas biopsies
      (endoscopic ultrasound examination [EUS]) yielded representative material in half
      of the cases. One exocrine fistula was treated by endoscopic stenting. PTxs-DD
      were associated with a higher rate of thrombosis compared to PTx-DJ (23% vs. 5%)
      and reoperations (48% vs. 30%), as well as inferior graft survival (80% vs. 88%).
      Time on waiting list, HLA A + B mismatches and reoperations were associated with
      graft loss. Only recipient age remained an independent predictor of patient death
      in multivariate analysis. PTx-DD showed a higher rate of thrombosis and inferior
      results, but facilitated a protocol biopsy program by EUS that was feasible and
      safe. Given that technical difficulties can be solved, the improved endoscopic
      access might confer long-term benefits, yet this remains to be proven.

PMID- 25394775
TI  - Utility of obesity indicators for metabolically healthy obesity: an observational
      study using the Korean National Health and Nutrition Examination Survey (2009
      2010).
AB  - BACKGROUND: Obese individuals who are not at an elevated risk for cardiovascular
      disease are described as having metabolically healthy obesity (MHO). We sought to
      identify clinically useful indicators of MHO. METHODS: Records of the Korean
      National Health and Nutrition Examination Survey (2009-2010) were used to analyze
      3,770 obese subjects (body mass index >= 25 kg/m2), who were divided into
      metabolic syndrome and MHO groups. Persons who met less than 3 of the criteria of
      metabolic syndrome (MS) were defined as having MHO. We estimated age-specific
      prevalence rates according to the number of MS criteria that were satisfied
      (patients meeting 0, <=1, and <=2 criteria of MS). Receiver operating
      characteristic analysis was performed to identify the best indicators of MHO.
      RESULTS: The prevalence of MHO among obese patients decreased with age. When MHO
      was defined by the fulfillment of <=2 criteria of MS, the areas under the curves
      (AUC) for waist circumference and waist-to-height ratio were 0.743 and 0.747 in
      men and 0.712 and 0.741 in women, respectively. Waist circumference and waist-to
      height ratio were the most accurate predictors of MHO for all investigated
      definitions. CONCLUSIONS: Waist circumference and waist-to-height ratio provide
      useful indicators for diagnosing MHO, and are more accurate than body mass index,
      fat percentage, or weight-adjusted appendicular skeletal muscle mass in the
      Korean population.

PMID- 25394774
TI  - TrkB inhibition by GNF-4256 slows growth and enhances chemotherapeutic efficacy
      in neuroblastoma xenografts.
AB  - PURPOSE: Neuroblastoma (NB) is one of the most common and deadly pediatric solid
      tumors. NB is characterized by clinical heterogeneity, from spontaneous
      regression to relentless progression despite intensive multimodality therapy.
      There is compelling evidence that members of the tropomyosin receptor kinase
      (Trk) family play important roles in these disparate clinical behaviors. Indeed,
      TrkB and its ligand, brain-derived neurotrophic factor (BDNF), are expressed in
      50-60 % of high-risk NBs. The BDNF/TrkB autocrine pathway enhances survival,
      invasion, metastasis, angiogenesis and drug resistance. METHODS: We tested a
      novel pan-Trk inhibitor, GNF-4256 (Genomics Institute of the Novartis Research
      Foundation), in vitro and in vivo in a nu/nu athymic xenograft mouse model to
      determine its efficacy in inhibiting the growth of TrkB-expressing human NB cells
      (SY5Y-TrkB). Additionally, we assessed the ability of GNF-4256 to enhance NB cell
      growth inhibition in vitro and in vivo, when combined with conventional
      chemotherapeutic agents, irinotecan and temozolomide (Irino-TMZ). RESULTS: GNF
      4256 inhibits TrkB phosphorylation and the in vitro growth of TrkB-expressing NBs
      in a dose-dependent manner, with an IC50 around 7 and 50 nM, respectively.
      Furthermore, GNF-4256 inhibits the growth of NB xenografts as a single agent (p <
      0.0001 for mice treated at 40 or 100 mg/kg BID, compared to controls), and it
      significantly enhances the antitumor efficacy of irinotecan plus temozolomide
      (Irino-TMZ, p < 0.0071 compared to Irino-TMZ alone). CONCLUSIONS: Our data
      suggest that GNF-4256 is a potent and specific Trk inhibitor capable of
      significantly slowing SY5Y-TrkB growth, both in vitro and in vivo. More
      importantly, the addition of GNF-4256 significantly enhanced the antitumor
      efficacy of Irino-TMZ, as measured by in vitro and in vivo growth inhibition and
      increased event-free survival in a mouse xenograft model, without additional
      toxicity. These data strongly suggest that inhibition of TrkB with GNF-4256 can
      enhance the efficacy of current chemotherapeutic treatment for
      recurrent/refractory high-risk NBs with minimal or no additional toxicity.

PMID- 25394776
TI  - Stratification based on methylation of TBX2 and TBX3 into three molecular grades
      predicts progression in patients with pTa-bladder cancer.
AB  - The potential risk of recurrence and progression in patients with non-muscle
      invasive bladder cancer necessitates followup by cystoscopy. The risk of
      progression to muscle-invasive bladder cancer is estimated based on the European
      Organisation of Research and Treatment of Cancer score, a combination of several
      clinicopathological variables. However, pathological assessment is not objective
      and reproducibility is insufficient. The use of molecular markers could
      contribute to the estimation of tumor aggressiveness. We recently demonstrated
      that methylation of GATA2, TBX2, TBX3, and ZIC4 genes could predict progression
      in Ta tumors. In this study, we aimed to validate the markers in a large patient
      set using DNA from formalin-fixed and paraffin-embedded tissue. PALGA: the Dutch
      Pathology Registry was used for patient selection. We included 192 patients with
      pTaG1/2 bladder cancer of whom 77 experienced progression. Methylation analysis
      was performed and log-rank analysis was used to calculate the predictive value of
      each methylation marker for developing progression over time. This analysis
      showed better progression-free survival in patients with low methylation rates
      compared with the patients with high methylation rates for all markers (P<0.001)
      during a followup of ten-years. The combined predictive effect of the methylation
      markers was analyzed with the Cox-regression method. In this analysis, TBX2,
      TBX3, and ZIC4 were independent predictors of progression. On the basis of
      methylation status of TBX2 and TBX3, patients were divided into three new
      molecular grade groups. Survival analysis showed that only 8% of patients in the
      low molecular grade group progressed within 5 years. This was 29 and 63% for the
      intermediate- and high-molecular grade groups. In conclusion, this new molecular
      grade based on the combination of TBX2 and TBX3 methylation is an excellent
      marker for predicting progression to muscle-invasive bladder cancer in patients
      with primary pTaG1/2 bladder cancer. 

PMID- 25394777
TI  - Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the
      Merkel cell polyomavirus.
AB  - Merkel cell carcinoma is a rare, highly aggressive cutaneous neuroendocrine
      carcinoma most commonly seen in sun-damaged skin. Histologically, the tumor
      consists of primitive round cells with fine chromatin and numerous mitoses.
      Immunohistochemical stains demonstrate expression of neuroendocrine markers. In
      addition, cytokeratin 20 (CK20) is expressed in ~95% of cases. In 2008, Merkel
      cell carcinoma was shown to be associated with a virus now known as Merkel cell
      polyomavirus in ~80% of cases. Prognostic and mechanistic differences between
      Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative Merkel
      cell carcinoma may exist. There has been the suggestion that CK20-negative Merkel
      cell carcinomas less frequently harbor Merkel cell polyomavirus, but a systematic
      investigation for Merkel cell polyomavirus incidence in CK20-negative Merkel cell
      carcinoma has not been done. To test the hypothesis that Merkel cell polyomavirus
      is less frequently associated with CK20-negative Merkel cell carcinoma, we
      investigated 13 CK20-negative Merkel cell carcinomas from the files of the
      Cleveland Clinic and the University of Michigan for the virus. The presence or
      absence of Merkel cell polyomavirus was determined by quantitative PCR performed
      for Large T and small T antigens, with sequencing of PCR products to confirm the
      presence of Merkel cell polyomavirus. Ten of these (77%) were negative for Merkel
      cell polyomavirus and three (23%) were positive for Merkel cell polyomavirus.
      Merkel cell polyomavirus is less common in CK20-negative Merkel cell carcinoma.
      Larger series and clinical follow-up may help to determine whether CK20-negative
      Merkel cell carcinoma is mechanistically and prognostically unique. 

PMID- 25394779
TI  - Marital status, childlessness, and social support among older Canadians.
AB  - Despite evidence of increasing diversification of family structures, little is
      known regarding implications of marital and parental status for access to social
      support in later life. Using data from Statistics Canada's 2007 General Social
      Survey, this study assessed the impact of marital and parental status
      intersections on social support among adults aged 60 and older (n = 11,503). Two
      stage probit regression models indicated that among those who were currently
      married or separated/divorced, childless individuals were more likely to report
      instrumental (domestic, transportation) and emotional support from people outside
      the household. Conversely, among never-married or widowed older adults, being
      childless was associated with reduced domestic support but without differences in
      other support domains. Findings suggest that marital and parental status
      intersections are not uniformly positive, neutral, or negative regarding
      implications for extra-household social support. Future work should address
      complexities of these relationships in order to better understand rapidly
      changing family structures.

PMID- 25394778
TI  - Clinicopathological analysis of endometrial carcinomas harboring somatic POLE
      exonuclease domain mutations.
AB  - The Cancer Genome Atlas described four major genomic groups of endometrial
      carcinomas, including a POLE ultramutated subtype comprising ~10% of endometrioid
      adenocarcinoma, characterized by POLE exonuclease domain mutations, ultrahigh
      somatic mutation rates, and favorable outcome. Our aim was to examine the
      morphological and clinicopathological features of ultramutated endometrial
      carcinomas harboring somatic POLE exonuclease domain mutations. Hematoxylin and
      eosin slides and pathology reports for 8/17 POLE-mutated endometrial carcinomas
      described in the Cancer Genome Atlas study were studied; for the remaining cases,
      virtual whole slide images publicly available at cBioPortal (www.cbioportal.org)
      were examined. A second cohort of eight POLE mutated endometrial carcinomas from
      University of Calgary was also studied. Median age was 55 years (range 33-87
      years). Nineteen patients presented as stage I, 1 stage II, and 5 stage III. The
      majority of cases (24 of the 25) demonstrated defining morphological features of
      endometrioid differentiation. The studied cases were frequently high grade (60%)
      and rich in tumor-infiltrating lymphocytes and/or peri-tumoral lymphocytes (84%);
      many tumors showed morphological heterogeneity (52%) and ambiguity (16%). Foci
      demonstrating severe nuclear atypia led to concern for serous carcinoma in 28% of
      cases. At the molecular level, the majority of the Cancer Genome Atlas POLE
      mutated tumors were microsatellite stable (65%), and TP53 mutations were present
      in 35% of cases. They also harbored mutations in PTEN (94%), FBXW7 (82%), ARID1A
      (76%), and PIK3CA (71%). All patients from both cohorts were alive without
      disease, and none of the patients developed recurrence at the time of follow-up
      (median 33 months; range 2-102 months). In conclusion, the recognition of
      ultramutated endometrial carcinomas with POLE exonuclease domain mutation is
      important given their favorable outcome. Our histopathological review revealed
      that these tumors are commonly high grade, have obvious lymphocytic infiltrates,
      and can show ambiguous morphology. As they frequently harbor TP53 mutations, it
      is important not to misclassify them as serous carcinoma. 

PMID- 25394780
TI  - Impact of providing care on the risk of leaving employment in Canada.
AB  - Population aging is likely to lead to an increase in the number of people in need
      of assistance. It is well known that a large part of this assistance originates,
      and will continue to originate, from the network of relatives and friends.
      However, the effects of the provision of care on individuals' employment
      trajectories when this care is combined with employment of varying intensity or
      with childcare responsibilities have rarely been examined. The present study used
      proportional hazards models with the General Social Survey, Cycles 20 and 21, to
      assess the impact of providing care to a partner, a parent or parent-in-law,
      another relative, or a non-relative on the risk of leaving employment. The
      analyses show that providing care to a parent or parent-in-law increases the
      probability of leaving employment only among women employed full-time and among
      men and women who have no children or only adult children.

PMID- 25394781
TI  - Development of reverse-transcription loop-mediated isothermal amplification assay
      for rapid detection of novel avian influenza A (H7N9) virus.
AB  - BACKGROUND: The emerged human infection with avian influenza A (H7N9) virus in
      China since 2013 has aroused global concerns. There is great demand for simple
      and rapid diagnostic method for early detection of H7N9 to provide timely
      treatment and disease control. The aim of the current study was to develop a
      rapid, accurate and feasible reverse-transcription loop-mediated isothermal
      amplification (RT-LAMP) assay for detection of H7N9 virus. RESULTS: The detection
      limits of the H7- and N9-specific RT-LAMP assay were both approximately 0.2 PFU
      per reaction. No cross-reactivity was observed with other subtype of influenza
      viruses or common respiratory viral pathogens. The assay worked well with
      clinical specimens from patients and chickens, and exhibited high specificity and
      sensitivity. CONCLUSIONS: The H7/N9 specific RT-LAMP assay was sensitive and
      accurate, which could be a useful alternative in clinical diagnostics of
      influenza A (H7N9) virus, especially in the hospitals and laboratories without
      sophisticated diagnostic systems.

PMID- 25394782
TI  - Detection of long-chain non-encoding RNA differential expression in non-small
      cell lung cancer by microarray analysis and preliminary verification.
AB  - Long-chain non-coding RNAs (lncRNAs) have been shown to be involved in the
      development and progression of non-small cell lung cancer (NSCLC). However, the
      roles of lncRNAs in NSCLC are not well understood. In this study, a high
      throughput microarray was used to compare the lncRNA and mRNA expression profiles
      in NSCLC and normal tissue (NT) samples. Several candidate adenocarcinoma
      associated lncRNAs were verified by reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR). Using abundant and varied probes, we were able to
      assess 30,586 lncRNAs and 26,109 coding transcripts in our microarray. It was
      observed that 1,242 lncRNAs and 1,102 mRNAs were differentially expressed (>=2
      fold change) in NSCLC compared with NT samples, indicating that numerous lncRNAs
      were significantly upregulated or downregulated in NSCLC. We also observed via RT
      qPCR that 10 lncRNAs were aberrantly expressed in NSCLC compared with
      histologically matched normal lung tissues. Among these, RP11-385J1.2 and TUBA4B
      were the most aberrantly expressed lncRNAs, as estimated by RT-qPCR in 90 pairs
      of NSCLC and NT samples. In conclusion, the present study detected the lncRNA
      expression patterns in NSCLC by microarray. The results revealed that a number of
      lncRNAs were differentially expressed in NSCLC tissues, suggesting that they may
      play a key role in tumor development.

PMID- 25394783
TI  - Evaluation of HAAH/humbug quantitative detection in the diagnosis of
      hepatocellular carcinoma.
AB  - Human aspartyl-(asparaginyl)-beta-hydroxylase (HAAH) is a type 2 transmembrane
      protein and an alpha-ketoglutarate-dependent dioxygenase that can
      stereospecifically catalyze the post-translational hydroxylation reaction of beta
      carbon atoms of aspartic acid and asparagine residues present in epidermal growth
      factor-like domains of certain specific proteins. Humbug is a truncated isoform
      of aspartyl (asparaginyl) beta-hydroxylase that lacks the catalytic domain. A
      series of reports demonstrated that overexpression of HAAH/humbug was identified
      in hepatocellular carcinoma (HCC) and various tumor tissues. However, the
      prognostic value of HAAH/humbug expression in HCC remains unclear. The purpose of
      this study was to investigate the expression of the HAAH/humbug gene at the mRNA
      and protein levels in HCC and to assess the overexpression of HAAH/humbug as a
      diagnostic and prognostic marker in HCC. HAAH/humbug mRNA levels were measured in
      120 HCCs and 40 paired non-tumor liver tissues by molecular beacon (MB)
      quantitative RT-PCR. Immunohistochemical staining was used to detect the protein
      level of the HAAH/humbug in the same specimens. ROC analysis was performed based
      on the expression levels of the HAAH/humbug gene in 120 cases of HCC tissues and
      40 cases of adjacent non-tumor liver tissues. The results showed that 117 (97.5%)
      of the 120 frozen sections of patients with HCCs had HAAH/humbug-positive
      immunoreactivity, whereas the 40 adjacent non-tumor liver tissues exhibited no
      staining. Higher levels of HAAH/humbug mRNA were found in 114 (95%) of the 120
      HCC tissues relative to the adjacent cancer-free tissue. ROC curve analysis
      exhibited that the sensitivity was 90.1%, specificity was 97.6% and ROC AUC was
      0.986. The specific value of HAAH/beta-actin abundance used as a cut-off point
      was 0.315, while the gene copy number (7.35 copies/ul) was used a as cut-off
      point, with sensitivity being 99.2%, specificity 96.7% and the ROC AUC used
      0.990. No statistically significant difference was observed for these two
      factors. HAAH/humbug expression levels were upregulated in almost all the HCC
      tissues when compared to the adjacent cancer-free tissue, irrespective of the cut
      off point used. Results of the present study suggested that HAAH/humbug is a
      potential diagnostic and prognostic biomarker for the treatment of HCC.

PMID- 25394784
TI  - Melasma Improving Spontaneously upon Switching from a Combined Oral Contraceptive
      to a Hormone-releasing Intrauterine Device: A Report of Four Cases.

PMID- 25394785
TI  - Exaggerated smooth muscle contraction segments on esophageal high-resolution
      manometry: prevalence and clinical relevance.
AB  - BACKGROUND: Two smooth muscle contraction segments (S2, S3) on esophageal high
      resolution manometry (HRM) demonstrate varying contraction vigor in symptomatic
      patients. Significance of isolated exaggerated smooth muscle contraction remains
      unclear. METHODS: High-resolution manometry studies were reviewed in 272
      consecutive patients (56.4 +/- 0.8 years, 62% F) and compared to 21 healthy
      controls (27.6 +/- 0.6 years, 52% F), using HRM tools (distal contractile
      integral, DCI; distal latency, DL; integrated relaxation pressure, IRP), Chicago
      Classification (CC) and multiple rapid swallows (MRS). Segments were designated
      merged when the trough between S2 and S3 was >=150 mmHg, and exaggerated S3 when
      peak S3 amplitude was >=150 mmHg without merging with S2. Presenting symptoms and
      global symptom severity (on 100 mm visual analog scale) were recorded. Prevalence
      of merged and exaggerated segments was determined, and characteristics compared
      to symptomatic patients with normal HRM, and to healthy controls. KEY RESULTS:
      Merged segments were identified in 5.6%, and exaggerated S3 in another 12.5%, but
      only 17-50% had a CC diagnosis; one healthy control had merged segments. DCI with
      wet swallows was similar in cohorts with merged and exaggerated segments (p =
      0.7), significantly higher than symptomatic patients with normal HRM and healthy
      controls (p <= 0.003 for each comparison). Incomplete inhibition and prominent
      DCI augmentation on MRS (p <= 0.01), and presenting symptoms (chest pain and
      dysphagia, p = 0.04) characterized exaggerated segments, but not demographics or
      symptom burden. CONCLUSIONS & INFERENCES: Merged esophageal smooth muscle
      segments and exaggerated S3 may represent hypermotility phenomena from abnormal
      inhibition and/or excitation, and are not uniformly identified by the CC
      algorithm.

PMID- 25394787
TI  - First-principles analysis of defect-mediated Li adsorption on graphene.
AB  - To evaluate the possible utility of single layer graphene for applications in Li
      ion batteries, an extensive series of periodic density functional theory (DFT)
      calculations are performed on graphene sheets with both point and extended
      defects for a wide range of lithium coverages. Consistent with recent reports, it
      is found that Li adsorption on defect-free single layer graphene is not
      thermodynamically favorable compared to bulk metallic Li. However, graphene
      surfaces activated by defects are generally found to bind Li more strongly, and
      the interaction strength is sensitive to both the nature of the defects and their
      densities. Double vacancy defects are found to have much stronger interactions
      with Li as compared to Stone-Wales defects, and increasing defect density also
      enhances the interaction of the Stone-Wales defects with Li. Li interaction with
      one-dimensional extended defects on graphene is additionally found to be strong
      and leads to increased Li adsorption. A rigorous thermodynamic analysis of these
      data establishes the theoretical Li storage capacities of the defected graphene
      structures. In some cases, these capacities are found to approach, although not
      exceed, those of graphite. The results provide new insights into the fundamental
      physics of adsorbate interactions with graphene defects and suggest that careful
      defect engineering of graphene might, ultimately, provide anode electrodes of
      suitable capacity for lithium ion battery applications. 

PMID- 25394786
TI  - Dopaminergic system dysfunction in recreational dexamphetamine users.
AB  - Dexamphetamine (dAMPH) is a stimulant drug that is widely used recreationally as
      well as for the treatment of attention-deficit hyperactivity disorder (ADHD).
      Although animal studies have shown neurotoxic effects of dAMPH on the
      dopaminergic system, little is known about such effects on the human brain. Here,
      we studied the dopaminergic system at multiple physiological levels in
      recreational dAMPH users and age, gender, and IQ-matched dAMPH-naive healthy
      controls. We assessed baseline D2/3 receptor availability, in addition to changes
      in dopamine (DA) release using single-photon emission computed tomography and DA
      functionality using pharmacological magnetic resonance imaging, following a dAMPH
      challenge. Also, the subjective responses to the challenge were determined. dAMPH
      users displayed significantly lower striatal DA D2/3 receptor binding compared
      with healthy controls. In dAMPH users, we further observed a blunted DA release
      and DA functionality to an acute dAMPH challenge, as well as a blunted subjective
      response. Finally, the lower D2/3 availability, the more pleasant the dAMPH
      administration was experienced by control subjects, but not by dAMPH users. Thus,
      in agreement with preclinical studies, we show that the recreational use of dAMPH
      in human subjects is associated with dopaminergic system dysfunction. These
      findings warrant further (longitudinal) investigations and call for caution when
      using this drug recreationally and for ADHD. 

PMID- 25394788
TI  - Gene expression profiling and association of circulating lactoferrin level with
      obesity-related phenotypes in Latino youth.
AB  - BACKGROUND/OBJECTIVES: Low-grade inflammation is an underlying feature of obesity
      and identifying inflammatory markers is crucial to understanding this disease.
      Therefore, the purpose of this study was twofold: (i) to perform a global
      microarray analysis and (ii) to investigate the role of lactoferrin (LTF), one of
      the most altered genes, in relation to obesity in Latino youth. METHODS: Non
      diabetic Latino youth (71 males/92 females; 15.6 +/- 3.2 years) were studied. A
      subset of 39 participants was randomly selected for global microarray analysis
      profiling from the whole blood sample. Serum LTF was compared between lean (n =
      78) and overweight/obese (n = 85) participants. RESULTS: Microarray analysis
      revealed that a total of 1870 probes were altered in expression >=1.2-fold and P
      < 0.05 in overweight/obese participants compared with lean. KEGG (Kyoto
      Encyclopedia of Genes and Genomes) analysis revealed significant enrichment for
      pathways including toll-like receptor (TLR) and B cell receptor signalling
      pathways. LTF and TLR5 were increased in expression by 2.2 and 1.5 fold,
      respectively, in the overweight/obese participants. Increased LTF concentrations
      were significantly associated with high risk of obesity-related phenotypes (all P
      < 0.05). CONCLUSIONS: Our data suggest that increased LTF is associated with
      obesity risk among Latino youth. This finding is discordant to what has been
      shown in adults and suggests that age may modulate the association between LTF
      and obesity-related health.

PMID- 25394789
TI  - Berberine targets epidermal growth factor receptor signaling to suppress prostate
      cancer proliferation in vitro.
AB  - Berberine is a well-known component of the Chinese herbal medicine Huanglian
      (Coptis chinensis), and is capable of inhibiting the proliferation of multiple
      cancer cell lines. However, information available regarding the effect of
      berberine on prostate cancer cell growth is limited. In the present study, LnCaP
      and PC-3 human prostate cancer cell lines were selected as in vitro models in
      order to assess the efficacy of berberine as an anticancer agent. A cell
      proliferation assay demonstrated that berberine inhibited cell growth in a dose
      and time-dependent manner. Further investigation revealed berberine significantly
      accumulated inside cells that were in the G1 phase of the cell cycle and enhanced
      apoptosis. Western blot analysis demonstrated that berberine inhibited the
      expression of prostate-specific antigen and the activation of epidermal growth
      factor receptor (EGFR), and it attenuated EGFR activation following EGF treatment
      in vitro. In conclusion, the results indicate that berberine inhibits the
      proliferation of prostate cancer cells through apoptosis and/or cell cycle arrest
      by inactivation of the EGFR signaling pathway.

PMID- 25394790
TI  - Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation
      of a noncoding intergenic element.
AB  - In certain human cancers, the expression of critical oncogenes is driven from
      large regulatory elements, called super-enhancers, that recruit much of the
      cell's transcriptional apparatus and are defined by extensive acetylation of
      histone H3 lysine 27 (H3K27ac). In a subset of T-cell acute lymphoblastic
      leukemia (T-ALL) cases, we found that heterozygous somatic mutations are acquired
      that introduce binding motifs for the MYB transcription factor in a precise
      noncoding site, which creates a super-enhancer upstream of the TAL1 oncogene. MYB
      binds to this new site and recruits its H3K27 acetylase-binding partner CBP, as
      well as core components of a major leukemogenic transcriptional complex that
      contains RUNX1, GATA-3, and TAL1 itself. Additionally, most endogenous super
      enhancers found in T-ALL cells are occupied by MYB and CBP, which suggests a
      general role for MYB in super-enhancer initiation. Thus, this study identifies a
      genetic mechanism responsible for the generation of oncogenic super-enhancers in
      malignant cells. 

PMID- 25394792
TI  - Paleomagnetism. Solar nebula magnetic fields recorded in the Semarkona meteorite.
AB  - Magnetic fields are proposed to have played a critical role in some of the most
      enigmatic processes of planetary formation by mediating the rapid accretion of
      disk material onto the central star and the formation of the first solids.
      However, there have been no experimental constraints on the intensity of these
      fields. Here we show that dusty olivine-bearing chondrules from the Semarkona
      meteorite were magnetized in a nebular field of 54 +/- 21 microteslas. This
      intensity supports chondrule formation by nebular shocks or planetesimal
      collisions rather than by electric currents, the x-wind, or other mechanisms near
      the Sun. This implies that background magnetic fields in the terrestrial planet
      forming region were likely 5 to 54 microteslas, which is sufficient to account
      for measured rates of mass and angular momentum transport in protoplanetary
      disks. 

PMID- 25394793
TI  - Cross-generational trans fat intake modifies BDNF mRNA in the hippocampus: Impact
      on memory loss in a mania animal model.
AB  - Recently, we have described the influence of dietary fatty acids (FA) on mania
      like behavior of first generation animals. Here, two sequential generations of
      female rats were supplemented with soybean oil (SO, rich in n-6 FA, control
      group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich
      in trans FA) from pregnancy and during lactation. In adulthood, half of each
      group was exposed to an amphetamine (AMPH)-induced mania animal model for
      behavioral, biochemical and molecular assessments. FO supplementation was
      associated with lower reactive species (RS) generation and protein carbonyl (PC)
      levels and increased dopamine transporter (DAT) levels, while HVF increased RS
      and PC levels, thus decreasing catalase (CAT) activity and DAT levels in
      hippocampus after AMPH treatment. AMPH impaired short- (1 h) and long- (24 h)
      term memory in the HVF group. AMPH exposure was able to reduce hippocampal BDNF-
      mRNA expression, which was increased in FO. While HVF was related to higher trans
      FA (TFA) incorporation in hippocampus, FO was associated with increased
      percentage of n-3 polyunsaturated FA (PUFA) together with lower n-6/n-3 PUFA
      ratio. Interestingly, our data showed a positive correlation between brain
      derived neurotrophic factor (BDNF) mRNA and short- and long-term memory (r(2)  =
      0.53; P = 0.000/r(2)  = 0.32; P = 0.011, respectively), as well as a negative
      correlation between PC and DAT levels (r(2)  = 0.23; P = 0.015). Our findings
      confirm that provision of n-3 or TFA during development over two generations is
      able to change the neuronal membrane lipid composition, protecting or impairing
      the hippocampus, respectively, thus affecting neurothrophic factor expression
      such as BDNF mRNA. In this context, chronic consumption of trans fats over two
      generations can facilitate the development of mania-like behavior, so leading to
      memory impairment and emotionality, which are related to neuropsychiatric
      conditions.

PMID- 25394791
TI  - Patient-derived models of acquired resistance can identify effective drug
      combinations for cancer.
AB  - Targeted cancer therapies have produced substantial clinical responses, but most
      tumors develop resistance to these drugs. Here, we describe a pharmacogenomic
      platform that facilitates rapid discovery of drug combinations that can overcome
      resistance. We established cell culture models derived from biopsy samples of
      lung cancer patients whose disease had progressed while on treatment with
      epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)
      tyrosine kinase inhibitors and then subjected these cells to genetic analyses and
      a pharmacological screen. Multiple effective drug combinations were identified.
      For example, the combination of ALK and MAPK kinase (MEK) inhibitors was active
      in an ALK-positive resistant tumor that had developed a MAP2K1 activating
      mutation, and the combination of EGFR and fibroblast growth factor receptor
      (FGFR) inhibitors was active in an EGFR mutant resistant cancer with a mutation
      in FGFR3. Combined ALK and SRC (pp60c-src) inhibition was effective in several
      ALK-driven patient-derived models, a result not predicted by genetic analysis
      alone. With further refinements, this strategy could help direct therapeutic
      choices for individual patients. 

PMID- 25394794
TI  - Localization of tobacco germin-like protein 1 in leaf intercellular space.
AB  - To characterize leaf cell wall proteins relating the architectural changes of
      leaves, we analyzed Nicotiana tabacum leaf cell wall proteins that were extracted
      by the treatment with lithium chloride. Some of these proteins showed amino acid
      sequence homology to some germin-like proteins (GLP). Based of those sequences,
      we isolated the cDNA encoding the GLPs (NtGLP1-1, NtGLP2-1). Phylogenetic
      analysis including de novo assembled tobacco GLPs using EST clones, revealed that
      tobacco GLPs belong to at least 5 different subgroups of GLP and both NtGLP1 and
      NtGLP2 belong to GLP subfamily 3. We showed that the NtGLP1 actually localizes to
      cell wall and revealed that it predominantly localized at specific sites on the
      leaf cell wall where intercellular attachment was just bifurcated. Expression of
      the NtGLP1 mRNA was mainly detected in leaves especially at elongating stage.
      NtGLP1 is possibly relevant to development of leaf intercellular space.

PMID- 25394795
TI  - Enzymatic conversion from pyridoxal to pyridoxine caused by  microorganisms
      within tobacco phyllosphere.
AB  - Vitamin B6 (VB6) comprises six interconvertible pyridine compounds (vitamers),
      among which pyridoxal 5'-phosphate (PLP) is a coenzyme involved in a high
      diversity of biochemical reactions. In plants, PLP is de novo synthesized, and
      pyridoxine (PN) is usually maintained as the predominant B6 vitamer. Although the
      conversion from pyridoxal (PL) to PN catalyzed by PL reductase in plants has been
      confirmed, the enzyme itself remains largely unknown. We previously found pre
      incubation at 35  degrees C dramatically enhanced PL reductase activity in
      tobacco leaf homogenate. In this study, we demonstrated that the increase in the
      reductase activity was a consequence of phyllosphere microbial proliferation. VB6
      was detected from tobacco phyllosphere, and PL level was the highest among three
      non-phosphorylated B6 vitamers. When the sterile tobacco rich in PL were kept in
      an open, warm and humid environment to promote microorganism proliferation, a
      significant change from PL to PN was observed. Our results suggest that there may
      be a plant-microbe interaction in the conversion from PL to PN within tobacco
      phyllosphere.

PMID- 25394796
TI  - Streptomyces rhizobacteria modulate the secondary metabolism of  Eucalyptus
      plants.
AB  - The genus Eucalyptus comprises economically important species, such as Eucalyptus
      grandis and Eucalyptus globulus, used especially as a raw material in many
      industrial sectors. Species of Eucalyptus are very susceptible to pathogens,
      mainly fungi, which leads to mortality of plant cuttings in rooting phase. One
      alternative to promote plant health and development is the potential use of
      microorganisms that act as agents for biological control, such as plant growth
      promoting rhizobacteria (PGPR). Rhizobacteria Streptomyces spp have been
      considered as PGPR. This study aimed at selecting strains of Streptomyces with
      ability to promote plant growth and modulate secondary metabolism of E. grandis
      and E. globulus in vitro plants. The experiments assessed the development of
      plants (root number and length), changes in key enzymes in plant defense
      (polyphenol oxidase and peroxidase) and induction of secondary compounds(total
      phenolic and quercetinic flavonoid fraction). The isolate Streptomyces PM9 showed
      highest production of indol-3-acetic acid and the best potential for root
      induction. Treatment of Eucalyptus roots with Streptomyces PM9 caused alterations
      in enzymes activities during the period of co-cultivation (1-15 days), as well as
      in the levels of phenolic compounds and flavonoids. Shoots also showed alteration
      in the secondary metabolism, suggesting induced systemic response. The ability of
      Streptomyces sp. PM9 on promoting root growth, through production of IAA, and
      possible role on modulation of secondary metabolism of Eucalyptus plants
      characterizes this isolate as PGPR and indicates its potential use as a
      biological control in forestry.

PMID- 25394797
TI  - Cultivar variability of iron uptake mechanisms in rice (Oryza sativa L.).
AB  - Rice (Oryza sativa L.) is the most important staple food in the world. It is rich
      in genetic diversity and can grow in a wide range of environments. Iron (Fe)
      deficiency is a major abiotic stress in crop production and in aerobic soils,
      where Fe forms insoluble complexes, and is not readily available for uptake. To
      cope with Fe deficiency, plants developed mechanisms for Fe uptake, and although
      rice was described as a Strategy II plant, recent evidence suggests that it is
      capable of utilizing mechanisms from both Strategies. The main objective of this
      work was to compare two cultivars, Bico Branco (japonica) and Nipponbare
      (tropical japonica), to understand if the regulation of Fe uptake mechanisms
      could be cultivar (cv.)dependent. Plants of both cultivars were grown under Fe
      deficient and -sufficient conditions and physiological and molecular responses to
      Fe deficiency were evaluated. Bico Branco cv. developed more leaf chlorosis and
      was more susceptible to Fe deficiency, retaining more nutrients in roots, than
      Nipponbare cv., which translocated more nutrients to shoots. Nipponbare cv.
      presented higher levels of Fe reductase activity, which was significantly up
      regulated by Fe deficiency, and had higher expression levels of the Strategy I
      OsFRO2 gene in roots, while Bico Branco cv. induced more genes involved in
      Strategy II.These new findings show that rice cultivars have different responses
      to Fe deficiency and that the induction of Strategy I or II may be rice cultivar
      dependent, although the utilization of the reduction mechanisms seems to be an
      ubiquitous advantage.

PMID- 25394798
TI  - Overexpression of codA gene confers enhanced tolerance to abiotic stresses in
      alfalfa.
AB  - We generated transgenic alfalfa plants (Medicago sativa L. cv. Xinjiang Daye)
      expressing a bacterial codA gene in chloroplasts under the control of the SWPA2
      promoter (referred to as SC plants) and evaluated the plants under various
      abiotic stress conditions. Three transgenic plants (SC7, SC8, and SC9) were
      selected for further characterization based on the strong expression levels of
      codA in response to methylviologen (MV)-mediated oxidative stress. SC plants
      showed enhanced tolerance to NaCl and drought stress on the whole plant level due
      to induced expression of codA. When plants were subjected to 250 mM NaCl
      treatment for 2 weeks, SC7 and SC8 plants maintained higher chlorophyll contents
      and lower malondialdehyde levels than non-transgenic (NT) plants. Under drought
      stress conditions, all SC plants showed enhanced tolerance to drought stress
      through maintaining high relative water contents and increased levels of
      glycinebetaine and proline compared to NT plants. Under normal conditions, SC
      plants exhibited increased growth due to increased expression of auxin-related
      IAA genes compared to NT plants. These results suggest that the SC plants
      generated in this study will be useful for enhanced biomass production on global
      marginal lands, such as high salinity and arid lands, yielding a sustainable
      agricultural product.

PMID- 25394799
TI  - Salts and nutrients present in regenerated waters induce changes in  water
      relations, antioxidative metabolism, ion accumulation and  restricted ion uptake
      in Myrtus communis L. plants.
AB  - The use of reclaimed water (RW) constitutes a valuable strategy for the efficient
      management of water and nutrients in landscaping. However, RW may contain levels
      of toxic ions, affecting plant production or quality, a very important aspect for
      ornamental plants. The present paper evaluates the effect of different quality
      RWs on physiological and biochemical parameters and the recovery capacity in
      Myrtus communis L. plants. M. communis plants were submitted to 3 irrigation
      treatments with RW from different sources (22 weeks): RW1 (1.7 dS m(-1)), RW2
      (4.0 dS m(-1)) and RW3 (8.0 dS m(-1)) and one control (C, 0.8 dS m(-1)). During a
      recovery period of 11 weeks, all plants were irrigated with the control water.
      The RW treatments did not negatively affect plant growth, while RW2 even led to
      an increase in biomass. After recovery,only plants irrigated with RW3 showed some
      negative effects on growth, which was related to a decrease in the net
      photosynthesis rate, higher Na accumulation and a reduction in K levels. An
      increase in salinity was accompanied by decreases in leaf water potential,
      relative water content and gas exchange parameters, and increases in Na and Cl
      uptake. Plants accumulated Na in roots and restricted its translocation to the
      aerial part. The highest salinity levels produced oxidative stress, as seen from
      the rise in electrolyte leakage and lipid peroxidation. The use of regenerated
      water together with carefully managed drainage practices, which avoid the
      accumulation of salt by the substrate, will provide economic and environmental
      benefits.

PMID- 25394800
TI  - Xanthomonas campestris lipooligosaccharides trigger innate immunity  and
      oxidative burst in Arabidopsis.
AB  - Plants lack the adaptive immunity mechanisms of jawed vertebrates, so they rely
      on innate immune responses to defense themselves from pathogens. The plant immune
      system perceives the presence of pathogens by recognition of molecules known as
      pathogen-associated molecular patterns (PAMPs). PAMPs have several common
      characteristics, including highly conserved structures, essential for the
      microorganism but absent in host organisms. Plants can specifically recognize
      PAMPs using a large set of receptors and can respond with appropriate defenses by
      activating a multicomponent and multilayered response. Lipopolysaccharides (LPSs)
      and lipooligosaccharides (LOSs) are major components of the cell surface of Gram
      negative bacteria with diverse roles in bacterial pathogenesis of animals and
      plants that include elicitation of host defenses. Little is known on the
      mechanisms of perception of these molecules by plants and the associated signal
      transduction pathways that trigger plant immunity.Here we addressed the question
      whether the defense signaling pathway in Arabidopsis thaliana was triggered by
      LOS from Xanthomonas campestris pv. campestris (Xcc), using proteomic and
      transcriptomic approaches. By using affinity capture strategies with immobilized
      LOS and LC-MS/MS analyses, we identified 8 putative LOS protein ligands. Further
      investigation of these interactors led to the definition that LOS challenge is
      able to activate a signal transduction pathway that uses nodal regulators in
      common with salicylic acid-mediated pathway. Moreover, we proved evidence that
      Xcc LOS are responsible for oxidative burst in Arabidopsis either in infiltrated
      or systemic leaves. In addition, gene expression studies highlighted the presence
      of gene network involved in reactive oxygen species transduction pathway.

PMID- 25394801
TI  - Aluminum stress inhibits root growth and alters physiological and  metabolic
      responses in chickpea (Cicer arietinum L.).
AB  - Chickpea (Cicer arietinum L.) roots were treated with aluminum (Al3+) in calcium
      chloride (CaCl2) solution (pH 4.7) and growth responses along with physiological
      and metabolic changes were investigated. Al3+ treatment for 7d resulted in a dose
      dependent decline of seed germination and inhibition of root growth. A
      significant (p <= 0.05) decline in fresh and dry biomass were observed after 7d
      of Al3+ stress.The root growth (length) was inhibited after 24 and 48 h of stress
      imposition. The hydrogen peroxide (H2O2) levels increased significantly (p <=
      0.05) with respect to control in Al3+ treated roots. The hematoxylin and Evans
      blue assay indicated significant (p <= 0.05) accumulation of Al3+ in the roots
      and loss of plasma membrane integrity respectively. The time-course evaluation of
      lipid peroxidation showed increase in malondialdehyde (MDA) after 12, 24 and 48 h
      of stress imposition. Al3+ treatment did not alter the MDA levels after 2 or 4 h
      of stress, however, a minor increase was observed after 6 and 10 h of treatment.
      The proton (1H) nuclear magnetic resonance (NMR) spectrum of the perchloric acid
      extracts showed variation in the abundance of metabolites and suggested a major
      metabolic shift in chickpea root during Al3+ stress. The key differences that
      were observed include changes in energy metabolites. Accumulation of phenolic
      compounds suggested its possible role in Al3+ exclusion in roots during stress.
      The results suggested that Al3+ alters growth pattern in chickpea and induces
      reactive oxygen species (ROS) production that causes physiological and metabolic
      changes.

PMID- 25394802
TI  - Effect of desiccation on the dynamics of genome-wide DNA  methylation in orthodox
      seeds of Acer platanoides L.
AB  - 5-methylcytosine, an abundant epigenetic mark, plays an important role in the
      regulation of plant growth and development, but there is little information about
      stress-induced changes in DNA methylation in seeds. In the present study, changes
      in a global level of m5C were measured in orthodox seeds of Acer platanoides L.
      during seed desiccation from a WC of 1.04 to 0.05-0.06 g H2O g g(-1) dry mass (g
      g(-1)). Changes in the level of DNA methylation were measured using 2D TLC e
      based method. Quality of desiccated seeds was examined by germination and
      seedling emergence tests. Global m5C content (R2)increase was observed in
      embryonic axes isolated from seeds collected at a high WC of 1.04 g g(-1) after
      their desiccation to significantly lower WC of 0.17 and 0.19 g g(-1). Further
      desiccation of these seeds to a WC of 0.06 g g(-1), however, resulted in a
      significant DNA demethylation to R2 1/4 11.52-12.22%. Similar m5C decrease was
      observed in seeds which undergo maturation drying on the tree and had four times
      lower initial WC of 0.27 g g(-1) at the time of harvest, as they were dried to a
      WC of 0.05 g g(-1). These data confirm that desiccation induces changes in seed
      m5C levels. Results were validated by seed lots derived from tree different A.
      platanoides provenances. It is plausible that sine wave-like alterations in m5C
      amount may represent a specific response of orthodox seeds to drying and play a
      relevant role in desiccation tolerance in seeds.

PMID- 25394803
TI  - Functional reconstitution of a rice aquaporin water channel, PIP1;1, by a micro
      batchwise methodology.
AB  - Assessing the selectivity, regulation and physiological relevance of aquaporin
      membrane channels (AQPs)requires structural and functional studies of wild type
      and modified proteins. In particular, when characterizing their transport
      properties, reconstitution in isolation from native cellular or membrane
      processes is of pivotal importance. Here, we describe rapid and efficient
      incorporation of OsPIP1;1, a rice AQP, in liposomes at analytical scale. PIP1;1
      was produced as a histidine-tagged form, 10 His-OsPIP1;1, in an Escherichia coli
      based expression system. The recombinant protein was purified by affinity
      chromatography and incorporated into liposomes by a micro-batchwise technology
      using egg-yolk phospholipids and the non-polar Amberlite resin. PIP1;1
      proteoliposomes and control empty liposomes had good size homogeneity as seen by
      quasi-elastic light scattering and electron microscopy analyses. By stopped-flow
      light scattering, indicating correct protein folding of the incorporated protein,
      the osmotic water permeability exhibited by the PIP1;1 proteoliposomes was
      markedly higher than empty liposomes. Functional reconstitution of OsPIP1;1 was
      further confirmed by the low Arrhenius activation energy (3.37 kcal/mol) and
      sensitivity to HgCl2, a known AQP blocker, of the PIP1;1-mediated osmotic water
      conductance. These results provide a valuable contribution in fully elucidating
      the regulation and water-conducting property of PIP1;1, an AQP that needs to
      hetero-multimerize with AQPs of the PIP2 subgroupto reach the native plasma
      membrane and play its role. The micro-batchwise methodology is suitable for the
      functional reconstitution of whichever AQPs and other membrane transport
      proteins.

PMID- 25394804
TI  - Effects of UV-B radiation on anatomical characteristics, phenolic  compounds and
      gene expression of the phenylpropanoid pathway in  highbush blueberry leaves.
AB  - The effects of increased doses of UV-B radiation on anatomical, biochemical and
      molecular features of leaves of two highbush blueberry (Vaccinium corymbosum L.
      cv. Brigitta and Bluegold) genotypes were investigated. Plants were grown in a
      solid substrate and exposed to 0, 0.07, 0.12 and 0.19 Wm(-2) of biologically
      effective UV-B radiation for up to 72 h. Leaf thickness and the adaxial epidermis
      thickness fell more than 3-fold in both genotypes at the highest UV-B dose.
      Moreover, in Bluegold an evident disorganization in the different cell layers was
      observed at the highest UV-B radiation. A significant decrease in chlorophyll a/b
      after 6 h in Brigitta under the greater UV-B doses was observed. Anthocyanin and
      total phenolics were increased, especially at 0.19 Wm(-2), when compared to the
      control in both genotypes.Chlorogenic acid was the most abundant hydroxycinnamic
      acid in Brigitta, and was significantly higher (P <= 0.05) than in Bluegold
      leaves. Regarding the expression of phenylpropanoid genes, only the transcription
      factor VcMYBPA1 showed a significant and sustained induction at higher doses of
      UV-B radiation in both genotypes compared to the controls. Thus, the reduction of
      leaf thickness concomitant with a lower lipid peroxidation and rapid enhancement
      of secondary metabolites, accompanied by a stable induction of the VcMYBPA1
      transcription factor suggest a better performance against UV-B radiation of the
      Brigitta genotype.

PMID- 25394805
TI  - Effects of a randomized controlled recurrent fall prevention program on risk
      factors for falls in frail elderly living at home in rural communities.
AB  - BACKGROUND: Falling can lead to severe health issues in the elderly and
      importantly contributes to morbidity, death, immobility, hospitalization, and
      early entry to long-term care facilities. The aim of this study was to devise a
      recurrent fall prevention program for elderly women in rural areas.
      MATERIAL/METHODS: This study adopted an assessor-blinded, randomized, controlled
      trial methodology. Subjects were enrolled in a 12-week recurrent fall prevention
      program, which comprised strength training, balance training, and patient
      education. Muscle strength and endurance of the ankles and the lower extremities,
      static balance, dynamic balance, depression, compliance with preventive behavior
      related to falls, fear of falling, and fall self-efficacy at baseline and
      immediately after the program were assessed. Sixty-two subjects (mean age 69.2+/
      4.3 years old) completed the program--31 subjects in the experimental group and
      31 subjects in the control group. RESULTS: When the results of the program in the
      2 groups were compared, significant differences were found in ankle heel rise
      test, lower extremity heel rise test, dynamic balance, depression, compliance
      with fall preventative behavior, fear of falling, and fall self-efficacy
      (p<0.05), but no significant difference was found in static balance. CONCLUSIONS:
      This study shows that the fall prevention program described effectively improves
      muscle strength and endurance, balance, and psychological aspects in elderly
      women with a fall history.

PMID- 25394806
TI  - Structures and unexpected dynamic properties of phosphine oxides adsorbed on
      silica surfaces.
AB  - Solid-state NMR spectroscopy of selected phosphine oxides adsorbed on silica
      surfaces establishes the surface mobilities, even of phosphine oxides with high
      melting points. Crystal structures of the adducts Ph3 PO?HOSiPh3 and Cy3 PO?H2 O
      indicate that the interactions with silica involve hydrogen bonding of the P=O
      group to adsorbed water and surface silanol groups.

PMID- 25394807
TI  - Investigating the molecular genetic basis of heterosis for internode expansion in
      maize by microRNA transcriptomic deep sequencing.
AB  - Heterosis has been used widely in the breeding of maize and other crops and plays
      an important role in increasing yield, improving quality, and enhancing stress
      resistance, but its molecular mechanism is far from clear. To determine whether
      microRNA (miRNA)-dependent gene regulation is responsible for heterosis of
      elongating internodes below the ear and ear height in maize, a deep-sequencing
      strategy was applied to the elite hybrid Xundan20, which is currently cultivated
      widely in China, and its two parents. RNA was extracted from the eighth internode
      because it shows clear internode length heterosis. A total of 99 conserved maize
      miRNAs were detected in both the hybrid and parental lines. Most of these miRNAs
      were expressed nonadditively in the hybrid compared with its parental lines.
      These results indicated that miRNAs might participate in heterosis during
      internode expansion in maize and exert an influence on ear and plant height via
      the repression of their target genes. In total, eight novel miRNAs belonging to
      four miRNA families were predicted in the expanding internode. Global repression
      of miRNAs in the hybrid, which might result in enhanced gene expression, might be
      one reason why the hybrid shows longer internodes and taller seedlings compared
      with its parental lines.

PMID- 25394808
TI  - Reproducibility of Acetabular Landmarks and a Standardized Coordinate System
      Obtained from 3D Hip Ultrasound.
AB  - Two-dimensional (2D) ultrasound detection of developmental dysplasia of the hip
      (DDH) is limited by variation in acetabular appearance and alpha angle
      measurements, which change with position of the ultrasound probe. Three
      dimensional (3D) ultrasound captures the entire acetabular shape, and a
      reproducible "standard central plane" may be generated, from two landmarks
      located on opposite ends of the acetabulum, for measurement of alpha angle and
      other indices. Two users identified landmarks on 51 3D ultrasounds, with ranging
      severity of disease, and inter- and intra-observer reproducibility of landmark
      and "standard plane" locations was compared; landmarks were chosen within 2 mm,
      and the "standard plane" rotation was reproducible within 10 degrees  between
      observers. We observed no difference in variability between alpha angles measured
      on the "standard plane" in comparison with 2D ultrasound. Applications of the
      standardized 3D ultrasound central plane will be to fuse serial ultrasounds for
      follow-up and development of new indices of 3D deformity. 

PMID- 25394809
TI  - Eccentric exercise 48 h prior to simulated diving has no effect on vascular
      bubble formation in rats.
AB  - PURPOSE: Decompression sickness (DCS) caused by vascular bubble formation is a
      major risk when diving. Prior studies have shown that physical exercise has a
      significant impact in both reducing and increasing bubble formation. There is
      limited knowledge about the mechanisms, but there are indications that exercise
      induced muscle injury prior to diving may cause increased bubble formation. The
      purpose of this study was to investigate the role of exercise-induced muscle
      injury as a possible mechanism of bubble formation during diving. METHODS: Muscle
      injury was induced by exposing female Sprague-Dawley rats (n = 30) to a single
      bout of eccentric exercise, 100 min intermittent, downhill (-16 degrees )
      treadmill running. Forty-eight hours later, the animals were exposed to a 50-min
      simulated saturation dive (709 kPa) in a pressure chamber, when the degree of
      muscle injury and inflammation would be the most pronounced. Bubble formation
      after the dive was observed by ultrasonic imaging for 4 h. RESULTS: No difference
      in bubble loads was found between the groups at any time despite evident muscle
      injury. Maximum bubble loads (bubbles cm(-2) heart cycle(-1)) were not different,
      exercise: 1.6 +/- 3.5 SD vs control: 2.2 +/- 4.1 SD, P = 0.90, n = 15 in each
      group. CONCLUSIONS: Eccentric exercise performed 48 h prior to diving causes
      skeletal muscle injury but does not increase the amount of vascular bubbles in
      rats. The prevailing recommendation is that physical activity prior to diving is
      a risk factor of DCS. However, present and previous studies implicate that pre
      dive physical activity does not increase the DCS risk.

PMID- 25394810
TI  - Immunosuppression with tacrolimus improved reproductive outcome of women with
      repeated implantation failure and elevated peripheral blood TH1/TH2 cell ratios.
AB  - PROBLEM: We evaluated the clinical efficacy of immunosuppressive treatment with
      tacrolimus for repeated implantation failure (RIF) patients who have elevated in
      T helper (Th1)/Th2 cytokine producing cell ratios. METHOD OF STUDY: This was a
      prospective cohort study of treatment for RIF patients (n = 42) with elevated
      peripheral blood Th1 (CD4(+) /IFN-gamma(+) )/Th2 (CD4(+) /IL-4(+) ) cell ratios
      at the Sugiyama clinic between November 2011 and October 2013. Twenty-five
      patients were treated with tacrolimus (treatment group) and 17 received no
      treatment (control group). Treatment group received tacrolimus 2 days before
      embryo transfer and continued until the day of the pregnancy test, for a total of
      16 days. The daily dose of tacrolimus (1-3 mg) was determined based on the degree
      of the Th1/Th2 cell ratio. RESULTS: The clinical pregnancy rate of the treatment
      group was 64.0%, which was significantly higher than that of the control group
      (0%) (P < 0.0001). In the treatment group, the miscarriage rate was 6.3%, the
      live birthrate was 60.0% (P < 0.0001). There was no significant side-effect from
      tacrolimus in treatment group. No one developed obstetrical complications during
      pregnancy. CONCLUSION: An immunosuppressive treatment using tacrolimus improved
      pregnancy outcome of repeated implantation failure patients with elevated Th1/Th2
      ratios.

PMID- 25394811
TI  - Evidence-based practice versus evidence-informed practice: a debate that could
      stall forward momentum in improving healthcare quality, safety, patient outcomes,
      and costs.

PMID- 25394812
TI  - N-heterocyclic carbene catalyzed enantioselective alpha-fluorination of aliphatic
      aldehydes and alpha-chloro aldehydes: synthesis of alpha-fluoro esters, amides,
      and thioesters.
AB  - The asymmetric fluorination of azolium enolates that are generated from readily
      available simple aliphatic aldehydes or alpha-chloro aldehydes and N-heterocyclic
      carbenes (NHCs) is described. The process significantly expands the synthetic
      utility of NHC-catalyzed fluorination and provides facile access to a wide range
      of alpha-fluoro esters, amides, and thioesters with excellent enantioselectivity.
      Pyrazole was identified as an excellent acyl transfer reagent for catalytic amide
      formation. 

PMID- 25394813
TI  - Maternal diet and its influence on the development of allergic disease.
AB  - The early presentation of childhood allergies and the rise in their prevalence
      suggest that changes in early-life exposures may increase the predisposition.
      Very early-life exposures may act upon the developing foetal immune system and
      include infection, environmental tobacco smoke, other pollutants and nutrients
      provided via the mother. Three nutrients have come under close scrutiny: vitamin
      D, omega 3 polyunsaturated fatty acids (PUFAs) and folate (or the synthetic form,
      folic acid). Much of the data on these nutrients are observational although some
      randomised, placebo-controlled trials have been conducted with omega 3 PUFAs and
      one with vitamin D. Some studies with omega 3 PUFA supplements in pregnancy have
      demonstrated immunomodulatory effects on the neonate and a reduction in risk of
      early sensitisation to allergens. A few studies with omega 3 polyunsaturated
      fatty acid supplements in pregnancy have shown a reduction in proportion of
      children affected by allergic symptoms (food allergy) or in symptom severity
      (atopic dermatitis). Observational studies investigating the association of
      maternal vitamin D intake or maternal or neonatal vitamin D status have been
      inconsistent. One randomised, controlled trial of vitamin D supplementation
      during pregnancy did not show any significant effect on allergic outcome in the
      offspring. Studies investigating the association between maternal folic acid or
      folate intake or maternal or neonatal folate status and offspring risk of
      allergic disease have been equivocal. Further evidence is required to clarify
      whether increased intake of these nutrients during pregnancy influences allergic
      disease in the offspring. In the light of current evidence, mothers should not
      either increase or avoid consuming these nutrients to prevent or ameliorate
      allergic disease in their offspring. However, these essential nutrients each have
      important roles in foetal development. This is reflected in current government
      recommendations for intake of these nutrients by pregnant women. 

PMID- 25394814
TI  - Force is a signal that cells cannot ignore.
AB  - Cells sense biochemical, electrical, and mechanical cues in their environment
      that affect their differentiation and behavior. Unlike biochemical and electrical
      signals, mechanical signals can propagate without the diffusion of proteins or
      ions; instead, forces are transmitted through mechanically stiff structures,
      flowing, for example, through cytoskeletal elements such as microtubules or
      filamentous actin. The molecular details underlying how cells respond to force
      are only beginning to be understood. Here we review tools for probing force
      sensitive proteins and highlight several examples in which forces are
      transmitted, routed, and sensed by proteins in cells. We suggest that local
      unfolding and tension-dependent removal of autoinhibitory domains are common
      features in force-sensitive proteins and that force-sensitive proteins may be
      commonplace wherever forces are transmitted between and within cells. Because
      mechanical forces are inherent in the cellular environment, force is a signal
      that cells must take advantage of to maintain homeostasis and carry out their
      functions. 

PMID- 25394816
TI  - Do weight perceptions among obese adults in Great Britain match clinical
      definitions? Analysis of cross-sectional surveys from 2007 and 2012.
AB  - OBJECTIVES: To assess the proportion of the adult obese population in Great
      Britain who would describe their weight using the terms 'obese' and 'very
      overweight' in 2007 and 2012, and identify factors associated with more accurate
      weight perceptions. DESIGN: Analysis of weight perception data from two
      population-based surveys. SETTING: Population surveys conducted in Great Britain.
      PARTICIPANTS: Survey respondents (N=657) whose self-reported weight and height
      placed them in the obese category: body mass index (BMI) >=30. PRIMARY OUTCOME
      MEASURE: Self-identification using the terms 'obese' and 'very overweight'.
      RESULTS: The proportion of obese adults selecting the term 'obese' to describe
      their body size was very low in both women (13% in 2007 and 11% in 2012) and men
      (4% in 2007 and 7% in 2012) and did not change significantly. Recognition of a
      substantial degree of overweight (as indexed by endorsement of either of the
      terms 'obese' or 'very overweight') declined substantially in women, from 50% in
      2007 to 34% in 2012. It was not significantly changed in men (27% in 2007 and 23%
      in 2012). Having a higher BMI, and being able to identify the BMI threshold for
      obesity were associated with self-identifying as obese or very overweight.
      CONCLUSIONS: The majority of the adult obese population of Great Britain do not
      identify themselves as either 'obese' or even 'very overweight'. Public health
      initiatives to tackle obesity are likely to be hampered by this lack of
      recognition of weight status. It is important to understand whether moves to
      increase personal awareness of weight status in the obese population can
      facilitate beneficial behaviour change, and what role health professionals can
      play in increasing awareness of weight status in obese patients.

PMID- 25394817
TI  - Can the painDETECT Questionnaire score and MRI help predict treatment outcome in
      rheumatoid arthritis: protocol for the Frederiksberg hospital's Rheumatoid
      Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study.
AB  - INTRODUCTION: Pain in rheumatoid arthritis (RA) is traditionally considered to be
      of inflammatory origin. Despite better control of inflammation, some patients
      still report pain as a significant concern, even when being in clinical
      remission. This suggests that RA may prompt central sensitisation-one aspect of
      chronic pain. In contrast, other patients report good treatment response,
      although imaging shows signs of inflammation, which could indicate a possible
      enhancement of descending pain inhibitory mechanisms. When assessing disease
      activity in patients with central sensitisation, the commonly used disease
      activity scores (eg, DAS28-CRP (C reactive protein)) will yield constant high
      total scores due to high tender joint count and global health assessments,
      whereas MRI provides an isolated estimate of inflammation. The objective of this
      study is, in patients with RA initiating anti-inflammatory treatment, to explore
      the prognostic value of a screening questionnaire for central sensitisation, hand
      inflammation assessed by conventional MRI, and the interaction between them
      regarding treatment outcome evaluated by clinical status (DAS28-CRP). For the
      purpose of further exploratory analyses, dynamic contrast-enhanced MRI (DCE-MRI)
      is performed. METHOD AND ANALYSIS: The painDETECT Questionnaire (PDQ), originally
      developed to screen for a neuropathic pain component, is applied to indicate the
      presence of central sensitisation. Adults diagnosed with RA are included when
      either (A) initiating disease-modifying antirheumatic drug treatment, or (B)
      initiating or switching to biological therapy. We anticipate that 100 patients
      will be enrolled, tested and reassessed after 4 months of treatment. DATA
      COLLECTION INCLUDES: Clinical data, conventional MRI, DCE-MRI, blood samples and
      patient-reported outcomes. ETHICS AND DISSEMINATION: This study aims at
      supporting rheumatologists to define strategies to reach optimal treatment
      outcomes in patients with RA based on chronic pain prognostics. The study has
      been approved by The Capital region of Denmark's Ethics Committee; identification
      number H-3-2013-049. The results will be published in international peer-reviewed
      journals.

PMID- 25394818
TI  - PC6 acupoint stimulation for the prevention of postcardiac surgery nausea and
      vomiting: a protocol for a two-group, parallel, superiority randomised clinical
      trial.
AB  - INTRODUCTION: Postoperative nausea and vomiting (PONV) are frequent but unwanted
      complications for patients following anaesthesia and cardiac surgery, affecting
      at least a third of patients, despite pharmacological treatment. The primary aim
      of the proposed research is to test the efficacy of PC6 acupoint stimulation
      versus placebo for reducing PONV in cardiac surgery patients. In conjunction with
      this we aim to develop an understanding of intervention fidelity and factors that
      support, or impede, the use of PC6 acupoint stimulation, a knowledge translation
      approach. METHODS AND ANALYSIS: 712 postcardiac surgery participants will be
      recruited to take part in a two-group, parallel, superiority, randomised
      controlled trial. Participants will be randomised to receive a wrist band on each
      wrist providing acupressure to PC six using acupoint stimulation or a placebo.
      Randomisation will be computer generated, use randomly varied block sizes, and be
      concealed prior to the enrolment of each patient. The wristbands will remain in
      place for 36 h. PONV will be evaluated by the assessment of both nausea and
      vomiting, use of rescue antiemetics, quality of recovery and cost. Patient
      satisfaction with PONV care will be measured and clinical staff interviewed about
      the clinical use, feasibility, acceptability and challenges of using acupressure
      wristbands for PONV. ETHICS AND DISSEMINATION: Ethics approval will be sought
      from appropriate Human Research Ethics Committee/s before start of the study. A
      systematic review of the use of wrist acupressure for PC6 acupoint stimulation
      reported minor side effects only. Study progress will be reviewed by a Data
      Safety Monitoring Committee (DSMC) for nausea and vomiting outcomes at n=350.
      Dissemination of results will include conference presentations at national and
      international scientific meetings and publications in peer-reviewed journals.
      Study participants will receive a one-page lay-summary of results. TRIAL
      REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry-
      ACTRN12614000589684.

PMID- 25394819
TI  - Governmental designation of spine specialty hospitals, their characteristics,
      performance and designation effects: a longitudinal study in Korea.
AB  - OBJECTIVES: This study compares the characteristics and performance of spine
      specialty hospitals versus other types of hospitals for inpatients with spinal
      diseases in South Korea. We also assessed the effect of the government's
      specialty hospital designation on hospital operating efficiency. SETTING: We used
      data of 823 hospitals including 17 spine specialty hospitals in Korea.
      PARTICIPANTS: All spine disease-related inpatient claims nationwide (N=645 449)
      during 2010-2012. INTERVENTIONS: No interventions were made. OUTCOME MEASURES:
      Using a multilevel generalised estimating equation and multilevel modelling, this
      study compared inpatient charges, length of stay (LOS), readmission within 30
      days of discharge and in-hospital death within 30 days of admission in spine
      specialty versus other types of hospitals. RESULTS: Spine specialty hospitals had
      higher inpatient charges per day (27.4%) and a shorter LOS (23.5%), but per case
      charges were similar after adjusting for patient-level and hospital-level
      confounders. After government designation, spine specialty hospitals had 8.8%
      lower per case charges, which was derived by reduced per day charge (7.6%) and
      shorter LOS (1.0%). Rates of readmission also were lower in spine specialty
      hospitals (OR=0.796). Patient-level and hospital-level factors both played
      important roles in determining outcome measures. CONCLUSIONS: Spine specialty
      hospitals had higher per day inpatient charges but a much shorter LOS than other
      types of hospitals due to their specialty volume and experience. In addition,
      their readmission rate was lower. Spine specialty hospitals also endeavoured to
      be more efficient after governmental 'specialty' designation.

PMID- 25394820
TI  - Prevalence and risk factors associated with prehypertension in Shunde District,
      southern China.
AB  - OBJECTIVE: To explore the prevalence and combined cardiovascular risk factors of
      prehypertension in southern China. DESIGN: A retrospective study; the logistic
      regression model was used to find the risk factors of prehypertension. SETTING:
      The study was conducted in Shunde District, southern China, using the community
      based health check-up information. PARTICIPANTS: Participants aged >=35 years
      with complete health check-up information data between January 2011 and December
      2013 were enrolled and divided into hypertension, prehypertension and optimal
      blood pressure (BP) groups. Prehypertension was further divided into low-range
      (BP 120-129/80-84 mm Hg) and high-range (BP 130-139/85-89 mm Hg) subgroups.
      OUTCOME MEASURES: The prevalence of prehypertension and the combined
      cardiovascular risk factors within the prehypertensive subgroups. RESULTS: Of the
      5362 initially reviewed cases (aged >=35 years), 651 were excluded because of
      missing data. The proportions of optimal BP, prehypertension and hypertension
      were 39.1%, 38.6% and 22.3%, respectively. The average age, proportion of male
      sex, overweight, impaired fasting glucose (IFG), dyslipidaemia and hyperuricaemia
      were significantly higher in the prehypertension group than in the optimal BP
      group (all p <0.05). Compared with low-range prehypertension, the proportions of
      overweight, dyslipidaemia and IFG were higher in the high-range prehypertension
      group (all p<0.05). Multivariate logistic regression analysis showed that
      overweight (OR=2.84, 95% CI 1.55 to 5.20), male sex (OR=2.19, 95% CI 1.39 to
      3.45), age (per 10 years, OR=1.21, 95% CI 1.02 to 1.44, p=0.03) and
      hyperuricaemia (OR=1.70, 95% CI 1.14 to 2.54) were independent risk factors of
      prehypertension. CONCLUSIONS: Prehypertension is highly prevalent in southern
      China. Prehypertensive individuals presented with many other cardiovascular risk
      factors. There was heterogeneity of combined risk factors within the
      prehypertensive subgroups.

PMID- 25394821
TI  - Finding medical care for colorectal cancer symptoms: experiences among those
      facing financial barriers.
AB  - Financial barriers can substantially delay medical care seeking. Using patient
      narratives provided by 252 colorectal cancer patients, we explored the experience
      of financial barriers to care seeking. Of the 252 patients interviewed, 84
      identified financial barriers as a significant hurdle to obtaining health care
      for their colorectal cancer symptoms. Using verbatim transcripts of the
      narratives collected from patients between 2008 and 2010, three themes were
      identified: insurance status as a barrier (discussed by n = 84; 100% of
      subsample), finding medical care (discussed by n = 30; 36% of subsample) and,
      insurance companies as barriers (discussed by n = 7; 8% of subsample). Our
      analysis revealed that insurance status is more nuanced than the categories
      insured/uninsured and differentially affects how patients attempt to secure
      health care. While barriers to medical care for the uninsured have been well
      documented, the experiences of those who are underinsured are less well
      understood. To improve outcomes in these patients it is critical to understand
      how financial barriers to medical care are manifested. Even with anticipated
      changes of the Affordable Care Act, it remains important to understand how
      perceived financial barriers may be influencing patient behaviors, particularly
      those who have limited health care options due to insufficient health insurance
      coverage. 

PMID- 25394822
TI  - Aligning cost assessment with community-based participatory research: the Kin
      KeeperSM intervention.
AB  - The few existing economic evaluations of community-based health promotion
      interventions were reported retrospectively at the end of the trial. We report an
      evaluation of the costs of the Kin Keeper(SM) Cancer Prevention Intervention, a
      female family-focused educational intervention for underserved women applied to
      increase breast and cervical cancer screening by enhancing cancer literacy. The
      cost analysis was performed from the perspective of a health organization with
      established community partnerships adding the Kin Keeper family intervention in
      the future to an existing community health worker program. The cost of delivering
      the Kin Keeper intervention, including two cancer education home visits, was
      $151/family. Kin Keeper is an inexpensive educational intervention delivered by
      community health workers to promote breast and cervical screening, with strong
      fidelity and quality. Prospecting cost evaluations of community-based
      interventions are needed for making informed timely decisions on the adaptation
      and expansion of such programs. 

PMID- 25394823
TI  - Organizational member involvement in physical activity coalitions across the
      United States: development and testing of a novel survey instrument for assessing
      coalition functioning.
AB  - INTRODUCTION: Coalitions are often composed of member organizations. Member
      involvement is thought to be associated with coalition success. No instrument
      currently exists for evaluating organizational member involvement in physical
      activity coalitions. This study aimed to develop a survey instrument for
      evaluating organizational member involvement in physical activity coalitions. The
      study was carried out in three phases: (a) developing a draft survey, (b)
      assessing the content validity of the draft survey, and (c) assessing the
      underlying factor structure, reliability, and validity of the survey. METHOD: A
      cross-sectional design was employed. In Phase 1, a team of experts in survey
      development produced a draft survey. In Phase 2, the content validity of the
      draft survey was evaluated by a panel of individuals with expertise in physical
      activity coalitions. In Phase 3, the survey was administered to 120 individuals
      on local-, state-, and national-level physical activity coalitions. Responses
      were subjected to an exploratory factor analysis in order to determine the
      survey's underlying factor structure, reliability, and validity. RESULTS: Phases
      1 and 2yielded a survey instrument with demonstrated content validity. Phase 3
      yielded a three-factor model with three subscales: Strategic Alignment,
      Organizational Alignment, and Providing Input. Each subscale demonstrated high
      internal consistency reliability and construct validity. DISCUSSION: The survey
      instrument developed here demonstrated sound psychometric properties and provides
      new insight into organizational member involvement in physical activity
      coalitions. This instrument may be an important tool in developing a more
      complete picture of coalition functioning in physical activity coalitions
      specifically and health-based coalitions overall.

PMID- 25394824
TI  - The association of social support and education with breast and cervical cancer
      screening.
AB  - BACKGROUND: Disparities in breast and cervical cancer screening by socioeconomic
      status persist in the United States. It has been suggested that social support
      may facilitate screening, especially among women of low socioeconomic status.
      However, at present, it is unclear whether social support enables mammogram and
      Pap test compliance. PURPOSE: This study examines the association between social
      support and compliance with mammogram and Pap test screening guidelines, and
      whether social support provides added value for women of low education. METHOD:
      Data were from a countywide 2009-2010 population-based survey, which included
      records of 2,588 women 40 years and older (mammogram) and 2,123 women 21 to 65
      years old (Pap test). Compliance was determined using the guidelines in effect at
      the time of data collection. RESULTS: Social support was significantly related to
      mammogram (adjusted odds ratio = 1.43; 95% confidence interval [1.16, 1.77]) and
      Pap test (adjusted odds ratio = 1.71; 95% confidence interval [1.27, 2.29])
      compliance after controlling for age, race, having a regular health care
      provider, and insurance status. The interaction between social support and
      education had a significant effect on Pap test compliance only among women
      younger than 40; the effect was not significant for mammogram compliance.
      CONCLUSION: Social support is associated with breast and cervical cancer
      screening compliance. The association between education and cancer screening
      behavior may be moderated by social support; however, results hold only for Pap
      tests among younger women. Practitioners and researchers should focus on
      interventions that activate social support networks as they may help increase
      both breast and cervical cancer screening compliance among women with low
      educational attainment.

PMID- 25394825
TI  - Beneficial effect of a high number of copies of salivary amylase AMY1 gene on
      obesity risk in Mexican children.
AB  - AIMS/HYPOTHESIS: Childhood obesity is a major public health problem in Mexico,
      affecting one in every three children. Genome-wide association studies identified
      genetic variants associated with childhood obesity, but a large missing
      heritability remains to be elucidated. We have recently shown a strong
      association between a highly polymorphic copy number variant encompassing the
      salivary amylase gene (AMY1 also known as AMY1A) and obesity in European and
      Asian adults. In the present study, we aimed to evaluate the association between
      AMY1 copy number and obesity in Mexican children. METHODS: We evaluated the
      number of AMY1 copies in 597 Mexican children (293 obese children and 304 normal
      weight controls) through highly sensitive digital PCR. The effect of AMY1 copy
      number on obesity status was assessed using a logistic regression model adjusted
      for age and sex. RESULTS: We identified a marked effect of AMY1 copy number on
      reduced risk of obesity (OR per estimated copy 0.84, with the number of copies
      ranging from one to 16 in this population; p = 4.25 * 10(-6)). The global
      association between AMY1 copy number and reduced risk of obesity seemed to be
      mostly driven by the contribution of the highest AMY1 copy number. Strikingly,
      all children with >10 AMY1 copies were normal weight controls.
      CONCLUSIONS/INTERPRETATION: Salivary amylase initiates the digestion of dietary
      starch, which is highly consumed in Mexico. Our current study suggests putative
      benefits of high number of AMY1 copies (and related production of salivary
      amylase) on energy metabolism in Mexican children.

PMID- 25394826
TI  - Effect of body position and oxygen tension on foramen ovale recruitment.
AB  - While there is an increased prevalence of stroke at altitude in individuals who
      are considered to be low risk for thrombotic events, it is uncertain how venous
      thrombi reach the brain. The patent foramen ovale (PFO) is a recruitable
      intracardiac shunt between the right and left atrium. We aimed to determine
      whether body position and oxygen tension affect blood flow through the PFO in
      healthy adults. We hypothesized that hypoxia and body positions that promote
      right atrial filling would independently recruit the PFO. Subjects with a PFO (n
      = 11) performed 11 trials, combining four different fractions of inhaled oxygen
      (FiO2) (1.0, 0.21, 0.15, and 0.10) and three positions (upright, supine, and 45
      degrees  head down), with the exception of FiO2 = 0.10, while 45 degrees  head
      down. After 5 min in each position, breathing the prescribed oxygen tension,
      saline bubbles were injected into an antecubital vein and a four-chamber
      echocardiogram was obtained to evaluate PFO recruitment. We observed a high
      incidence of PFO recruitment in all conditions, with increased recruitment in
      response to severe hypoxia and some contribution of body position at moderate
      levels of hypoxia. We suspect that increased pulmonary vascular pressure,
      secondary to hypoxia-induced pulmonary vasoconstriction, increased right atrial
      pressure enough to recruit the PFO. Additionally, we hypothesize that the minor
      increase in breathing resistance that was added by the mouthpiece, used during
      experimental trials, affected intrathoracic pressure and venous return
      sufficiently to recruit the PFO.

PMID- 25394827
TI  - Propranolol, but not naloxone, enhances spinal reflex bladder activity and
      reduces pudendal inhibition in cats.
AB  - This study examined the role of beta-adrenergic and opioid receptors in spinal
      reflex bladder activity and in the inhibition induced by pudendal nerve
      stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder
      contractions were induced by intravesical infusion of 0.25% acetic acid in alpha
      chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the
      thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal
      reflex contractions at 2 and 4 times the threshold intensity (T) for inducing
      anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and
      4T significantly (P < 0.05) increased bladder capacity from 58.0 +/- 4.7% to 85.8
      +/- 10.3% and 96.5 +/- 10.7%, respectively, of saline control capacity, while TNS
      failed to inhibit spinal reflex bladder contractions. After administering
      propranolol (3 mg/kg iv, a beta1/beta2-adrenergic receptor antagonist), the
      effects of 2T and 4T PNS on bladder capacity were significantly (P < 0.05)
      reduced to 64.5 +/- 9.5% and 64.7 +/- 7.3%, respectively, of the saline control
      capacity. However, the residual PNS inhibition (about 10% increase in capacity)
      was still statistically significant (P < 0.05). Propranolol treatment also
      significantly (P = 0.0019) increased the amplitude of bladder contractions but
      did not change the control bladder capacity. Naloxone (1 mg/kg iv, an opioid
      receptor antagonist) had no effect on either spinal reflex bladder contractions
      or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a
      ganglionic blocker) significantly (P < 0.05) reduced the amplitude of the reflex
      bladder contractions. This study indicates an important role of beta1/beta2
      adrenergic receptors in pudendal inhibition and spinal reflex bladder activity.

PMID- 25394828
TI  - NMDA-type glutamate receptors participate in reduction of food intake following
      hindbrain melanocortin receptor activation.
AB  - Hindbrain injection of a melanocortin-3/4 receptor agonist, MTII, reduces food
      intake primarily by reducing meal size. Our previously reported results indicate
      that N-methyl-D-aspartate-type glutamate receptors (NMDAR) in the nucleus of the
      solitary tract (NTS) play an important role in the control of meal size and food
      intake. Therefore, we hypothesized that activation of NTS NMDARs contribute to
      reduction of food intake in response to fourth ventricle or NTS injection of
      MTII. We found that coinjection of a competitive NMDAR antagonist (d-CPP-ene)
      with MTII into the fourth ventricle or directly into the NTS of adult male rats
      attenuated MTII-induced reduction of food intake. Hindbrain NMDAR antagonism also
      attenuated MTII-induced ERK1/2 phosphorylation in NTS neurons and prevented
      synapsin I phosphorylation in central vagal afferent endings, both of which are
      cellular mechanisms previously shown to participate in hindbrain
      melanocortinergic reduction of food intake. Together, our results indicate that
      NMDAR activation significantly contributes to reduction of food intake following
      hindbrain melanocortin receptor activation, and it participates in
      melanocortinergic signaling in NTS neural circuits that mediate reduction of food
      intake.

PMID- 25394829
TI  - The sleep-wake cycle and motor activity, but not temperature, are disrupted over
      the light-dark cycle in mice genetically depleted of serotonin.
AB  - We examined the role that serotonin has in the modulation of sleep and
      wakefulness across a 12-h:12-h light-dark cycle and determined whether
      temperature and motor activity are directly responsible for potential disruptions
      to arousal state. Telemetry transmitters were implanted in 24 wild-type mice
      (Tph2(+/+)) and 24 mice with a null mutation for tryptophan hydroxylase 2 (Tph2(
      /-)). After surgery, electroencephalography, core body temperature, and motor
      activity were recorded for 24 h. Temperature for a given arousal state (quiet and
      active wake, non-rapid eye movement, and paradoxical sleep) was similar in the
      Tph2(+/+) and Tph2(-/-) mice across the light-dark cycle. The percentage of time
      spent in active wakefulness, along with motor activity, was decreased in the
      Tph2(+/+) compared with the Tph2(-/-) mice at the start and end of the dark
      cycle. This difference persisted into the light cycle. In contrast, the time
      spent in a given arousal state was similar at the remaining time points. Despite
      this similarity, periods of non-rapid-eye-movement sleep and wakefulness were
      less consolidated in the Tph2(+/+) compared with the Tph2(-/-) mice throughout
      the light-dark cycle. We conclude that the depletion of serotonin does not
      disrupt the diurnal variation in the sleep-wake cycle, motor activity, and
      temperature. However, serotonin may suppress photic and nonphotic inputs that
      manifest at light-dark transitions and serve to shorten the ultraradian duration
      of wakefulness and non-rapid-eye-movement sleep. Finally, alterations in the
      sleep-wake cycle following depletion of serotonin are unrelated to disruptions in
      the modulation of temperature. 

PMID- 25394830
TI  - Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis
      in vitro and adrenal gene expression.
AB  - The classic renin-angiotensin system is partly responsible for controlling
      aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG
      II). In addition, there is a local adrenocortical renin-angiotensin system that
      may be involved in the control of aldosterone synthesis in the zona glomerulosa
      (ZG). To characterize the long-term control of adrenal steroidogenesis, we
      utilized adrenal glands from renin knockout (KO) rats and compared
      steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT)
      controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and
      subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were
      separately dispersed and studied in vitro. Plasma renin activity and ANG II
      concentrations were extremely low in the KO rats. Basal and cAMP-stimulated
      aldosterone production was significantly reduced in renin KO ZG cells, whereas
      corticosterone production was not different between WT and KO ZFR cells. As
      expected, adrenal renin mRNA expression was lower in the renin KO compared with
      the WT rat. Real-time PCR and immunohistochemical analysis showed a significant
      decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the
      renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO
      adrenal seems to be accounted for by a specific decrease in P450aldo and may be
      due to the absence of chronic stimulation of the ZG by circulating ANG II or to a
      reduction in locally released ANG II within the adrenal gland. 

PMID- 25394831
TI  - General practitioner views of an electronic high-risk medicine proforma to
      facilitate information transfer.
AB  - BACKGROUND: The potential of warfarin related harm is increased if clinicians
      lack the full patient specific information to make informed decisions-an e
      proforma has been developed to communicate this information on hospital
      discharge. OBJECTIVE: To determine the views of general practitioners (GPs) on a
      warfarin discharge e-proforma. METHOD: A cross-sectional survey of all GPs (n =
      272) within the Raigmore Hospital catchment area of NHS Highland, Scotland.
      RESULTS: The response rate was 39.3 % (107/272). 84 (78.5 %) noticed recent
      changes to information supplied on discharge for warfarin patients. 64 (59.8 %)
      respondents thought this would result in more informed prescribing with regards
      to dosing, while 65 (60.7 %) felt this would improve safety. Accurate completion,
      timely receipt of the e-proforma and a realistic date for subsequent INR tests
      were considered important by GPs. CONCLUSION: This study suggests the use of an e
      proforma to communicate information about a high-risk medication, warfarin, to
      GPs on discharge optimises safe, informed prescribing and monitoring in primary
      care. The development of a discharge e-proforma for other high-risk medication as
      a patient safety improvement measure should be explored.

PMID- 25394832
TI  - The real-life clinical effects of 52 weeks of omalizumab therapy for severe
      persistent allergic asthma.
AB  - BACKGROUND: Omalizumab was introduced in Malta in 2011. To date, no local data
      have been published. OBJECTIVE: To obtain baseline characteristics of our local
      cohort, determine effectiveness of omalizumab at 52 weeks, compare clinical
      outcomes 52 weeks pre- and postomalizumab therapy and to assess its safety and
      tolerability. SETTING: The Mater Dei Hospital in Malta. METHOD: All consented
      adult patients who were eligible to start treatment with omalizumab for asthma
      were enrolled in this open, prospective observational real-life study. A
      questionnaire was completed and an Asthma Control Test and spirometry performed.
      Patients were reviewed on a regular basis. Any undesirable symptoms were
      recorded. Treatment effectiveness was evaluated at 16 and 52 weeks, during which
      a decision was taken whether patients were responders. Outcomes were compared 52
      weeks pre- and post- treatment initiation. Main outcome measure To determine
      effectiveness of treatment following 1 year of omalizumab by assessing its impact
      on the rate of asthma-related exacerbations and health care utilization including
      hospitalizations. RESULTS: Our cohort included 22 patients, all non-smokers (mean
      age 52.7 +/- 11, 64 % males). The mean baseline IgE level was 448.6 +/- 444
      IU/ml. At week 12, treatment was stopped in one patient due to arthralgias. The
      drug was stopped in two patients at week 16 due to treatment ineffectiveness. At
      week 20, treatment was stopped in another patient in view of arthralgias. A
      significant reduction in the number of asthma exacerbations (p = .03) and number
      of systemic steroid courses required (p = .03) was identified at 52 weeks. There
      was a significant improvement in the ACT score (p < .001) after 52 weeks but no
      significant improvement in FEV1. There was a non-significant decline in the
      number of hospitalizations (p = .6), asthma-related healthcare visits (p = .2)
      and days off work (p = .09). Adverse events occurred in 10 % of patients. Costs
      related to asthma hospital-stay and medicines administered during
      hospitalisations were decreased by half following 1 year on omalizumab.
      CONCLUSION: Omalizumab treatment resulted in an improved asthma control, with a
      significant reduction in asthma exacerbations and systemic steroid courses
      required and improvement on ACT score. Adverse events were infrequent and the
      drug was well tolerated.

PMID- 25394833
TI  - An audit of the pharmacological management of ischaemic stroke patients in a
      metropolitan Australian hospital.
AB  - BACKGROUND: According to the Australian Bureau of Statistics, stroke is the
      second leading cause of death in Australia. The clinical Guidelines for stroke
      management published by the National Stroke Foundation provide a series of
      evidence based recommendations to assist clinicians in the management of stroke
      patients. Appropriate management of patients admitted to stroke units reduces
      death and disability by 20 %. Moreover, a multidisciplinary team approach also
      improves patient outcomes. OBJECTIVE: To retrospectively review the
      pharmacological management of ischaemic stroke patients in a metropolitan
      Australian hospital, and to compare adherence with the guidelines for stroke
      management with the national stroke foundation data with and without pharmacist
      intervention. METHOD: A retrospective audit of medical records was undertaken of
      all patients admitted to a large teaching hospital with the diagnosis of stroke
      or cerebral infarction from January 2013 to May 2013. RESULTS: A total of 124
      patients were included in the study. Most patients were discharged on appropriate
      pharmacological intervention for the prevention of secondary stroke:
      antihypertensive agents (71 %), lipid lowering agents (67 %) and antithrombotic
      (85 %) medications. CONCLUSION: The majority of the cohort was discharged on the
      appropriate evidence based medications for the management of secondary stroke.
      Further improvement may be achieved by pharmacist intervening as part of a
      multidisciplinary team.

PMID- 25394834
TI  - Development and Evaluation of the Curriculum for BOLD (Bronx Oncology Living
      Daily) Healthy Living: a Diabetes Prevention and Control Program for Underserved
      Cancer Survivors.
AB  - Underserved minority communities have few resources for addressing comorbidity
      risk reduction among long-term cancer survivors. To address this community need,
      we developed and piloted the Bronx Oncology Living Daily (BOLD) Healthy Living
      program, the first known diabetes prevention and control program to target cancer
      survivors and co-survivors in Bronx County, NY. The program aimed to facilitate
      lifestyle change and improve health-related quality of life (HRQoL) through
      weekly group nutrition education (60-90 min) and exercise (60 min) classes. We
      examined baseline characteristics of participants using simple descriptive
      statistics and evaluated program implementation and impact using the Reach,
      Efficacy, Adoption, Implementation and Maintenance (RE-AIM) framework. The
      curriculum, which drew from the social-ecological framework and motivational and
      cognitive behavioral strategies, consisted of 12 culturally and medically
      tailored modules with options for implementation as a 12- or 4-week program.
      Seven programs (four 12 weeks and three 4 weeks in length, respectively) were
      implemented at five community site locations. Sixty-six cancer survivors and 17
      cancer co-survivors (mean age 60.5 +/- 10.2 years) enrolled in one of the
      programs. Most participants were female (95.2 %) minority (55.4 % black, 26.5 %
      Hispanic/Latino) breast cancer survivors (75.7 %). Median program attendance was
      62.5 % and did not significantly differ by program length; however, 67.3 % of
      participants achieved >=60 % attendance among the 12-week programs, compared to
      41.9 % among the 4-week programs, and this difference was statistically
      significant (p = 0.02). Overall, participants reported significant pre/post
      improvements in perceived health as good/excellent (66.0 to 75.5 %; p = 0.001)
      and borderline significant decreases in perceived pain as moderate/severe (45.5
      to 38.2 %; p = 0.05). More than 90 % of participants reported that the program
      helped them to achieve their short-term goals, motivated them to engage in
      healthier behaviors, and felt that the nutrition and exercise classes were
      relevant to their needs. These results indicate that a short-term lifestyle
      intervention program for adult cancer survivors was acceptable in our community
      and motivated cancer survivors to improve their HRQoL. The curriculum can be used
      as a tool to facilitate development of similar programs in the future.

PMID- 25394837
TI  - Folic acid supplemented goat milk has beneficial effects on hepatic physiology,
      haematological status and antioxidant defence during chronic Fe repletion.
AB  - The aim of the current study was to asses the effect of goat or cow milk-based
      diets, either normal or Fe-overloaded and folic acid supplement on some aspects
      of hepatic physiology, enzymatic antioxidant defence and lipid peroxidation in
      liver, brain and erythrocyte of control and anaemic rats after chronic Fe
      repletion. 160 male Wistar rats were placed on 40 d in two groups, a control
      group receiving normal-Fe diet and the Fe-deficient group receiving low Fe diet.
      Lately, the rats were fed with goat and cow milk-based diets during 30 d, with
      normal-Fe content or Fe-overload and either with normal folic or folic acid
      supplemented. Fe-overload increased plasma alanine transaminase and aspartate
      transaminase levels when cow milk was supplied. Dietary folate supplementation
      reduced plasma transaminases levels in animals fed goat milk with chronic Fe
      overload. A remarkable increase in the superoxide dismutase activity was observed
      in the animals fed cow milk. Dietary folate supplement lead to a decrease on the
      activity of this enzyme in all the tissues studied with both milk-based diets. A
      concomitant increment in catalase was also observed. The increase in lipid
      peroxidation products levels in rats fed cow milk with Fe-overload, suggest an
      imbalance in the functioning of the enzymatic antioxidant defence. In conclusion,
      dietary folate-supplemented goat milk reduces both plasma transaminases levels,
      suggesting a hepatoprotective effect and has beneficial effects in situation of
      Fe-overload, improving the antioxidant enzymes activities and reducing lipid
      peroxidation. 

PMID- 25394838
TI  - [Valproate can induce reversible encephalopathy].
AB  - Valproate (VPA) is a widely used antiepileptic drug - also in the elderly. A
      female patient was diagnosed with epilepsy at the age of 60 years and treated
      with VPA for 16 years before developing tremor, rigidity, cognitive impairment
      and descending consciousness progressing to coma. After discontinuation of VPA
      she regained full consciousness, could talk and feed herself. The extrapyramidal
      and cognitive symptoms completely subsided during the following months. VPA
      induced encephalopathy is an uncommon but serious adverse effect that should be
      considered in patients with cognitive decline during VPA treatment. 

PMID- 25394836
TI  - Albumin administration is associated with acute kidney injury in cardiac surgery:
      a propensity score analysis.
AB  - INTRODUCTION: The risk of acute kidney injury (AKI) with the use of albumin
      containing fluids compared to starches in the surgical intensive care setting
      remains uncertain. We evaluated the adjusted risk of AKI associated with colloids
      following cardiac surgery. METHODS: We performed a retrospective cohort study of
      patients undergoing on-pump cardiac surgery in a tertiary care center from 2008
      to 2010. We assessed crystalloid and colloid administration until 36 hours after
      surgery. AKI was defined by the RIFLE (risk, injury, failure, loss and end-stage
      kidney disease) risk and Acute Kidney Injury Network (AKIN) stage 1 serum
      creatinine criterion within 96 hours after surgery. RESULTS: Our cohort included
      984 patients with a baseline glomerular filtration rate of 72 +/- 19 ml/min/1.73
      m(2). Twenty-three percent had a reduced left ventricular ejection fraction
      (LVEF), thirty-one percent were diabetics and twenty-three percent underwent
      heart valve surgery. The incidence of AKI was 5.3% based on RIFLE risk and 12.0%
      based on the AKIN criterion. AKI was associated with a reduced LVEF, diuretic
      use, anemia, heart valve surgery, duration of extracorporeal circulation,
      hemodynamic instability and the use of albumin, pentastarch 10% and transfusions.
      There was an important dose-dependent AKI risk associated with the administration
      of albumin, which also paralleled a higher prevalence of concomitant risk factors
      for AKI. To address any indication bias, we derived a propensity score predicting
      the likelihood to receive albumin and matched 141 cases to 141 controls with a
      similar risk profile. In this analysis, albumin was associated with an increased
      AKI risk (RIFLE risk: 12% versus 5%, P = 0.03; AKIN stage 1: 28% versus 13%, P =
      0.002). We repeated this methodology in patients without postoperative
      hemodynamic instability and still identified an association between the use of
      albumin and AKI. CONCLUSIONS: Albumin administration was associated with a dose
      dependent risk of AKI and remained significant using a propensity score
      methodology. Future studies should address the safety of albumin-containing
      fluids on kidney function in patients undergoing cardiac surgery.

PMID- 25394839
TI  - [Starvation is a rare cause of metabolic ketoacidosis].
AB  - A 79-year-old woman with no medical history was admitted under the diagnosis of
      stroke. Two months prior she had a fractured tibia, complicated by osteomyelitis.
      Physical examination showed dehydration and malnourishment. Chest X-ray revealed
      pneumonia and laboratory data revealed signs of infection, dehydration and
      normoglycaemic metabolic acidosis with elevated P-3-hydroxybutyrate. The case
      presents a starvation- (weight loss ~ 13 kg) and infection-induced non-diabetic
      metabolic ketoacidosis treated with intravenous supplementation of isotonic
      saline, potassium, bicarbonate and insulin. 

PMID- 25394840
TI  - [Cardiac myxomas may cause cerebral aneurysms].
AB  - Cerebral aneurysm following a cardiac myxoma is a rare neurological complication.
      We report a 50-year-old man who developed cerebral aneurysms one year after
      resection of a cardiac myxoma. Magnetic resonance imaging of the brain showed
      features of intracranial haemorrhage. Digital subtraction angiography showed
      several fusiform intracranial aneurysms bilaterally in the middle cerebral
      artery. Finally, we discuss potential molecular mechanisms of the development of
      myxomatous aneurysms. 

PMID- 25394841
TI  - [Amphetamine abuse and drug interactions].
AB  - Party drug consumption is a growing problem in Denmark. Often these drugs are
      taken in combination. In this article we review the pharmacodynamic and
      pharmacokinetic interactions between amphetamine, other illicit drugs and
      prescription medicine. 

PMID- 25394842
TI  - [Surprising squamous cell carcinoma in the right upper lobe at bronchoscopy in a
      heavy smoker].
AB  - A 60-year-old male heavy smoker surprisingly presented with a squamous cell
      carcinoma in the right upper lobe at bronchoscopy. Combined PET-CT classified the
      lung cancer as T1aN0M0. However, the endoscopic classification was T2a, which
      radically reversed the treatment schedule. CONCLUSIONS: 1) A careful bronchoscopy
      is important even in cases where lung cancer is not expected. 2) Accurate
      endobronchial classification can be crucial. 3) There is need for training
      requirements to obtain a satisfactory level of competence in bronchoscopy.

PMID- 25394843
TI  - [Late diagnostics and inadequate follow-up of asthma exacerbation].
AB  - Late diagnostics and inadequate follow-up of an asthma patient could have been
      avoided by use of accessible initiatives. Several differential diagnoses to
      dyspnoea and oppression of the chest exist and in this case a spirometry would
      have established the asthma diagnosis. Increasing specialization causes necessity
      to focus on differential diagnosis from nearby specialities. After
      hospitalization with asthma, the patient should be followed closely until asthma
      control is achieved and the necessary education is given so that inhalation
      technique and adherence is optimized. 

PMID- 25394844
TI  - [Cannabinoid hyperemesis syndrome should be considered by recurrent vomiting].
AB  - Cannabinoid hyperemesis syndrome (CHS) is characterised by unrelenting nausea,
      recurrent vomiting, abdominal pain and compulsive, hot bathing behaviour. The
      symptoms contrast the traditional effects associated with cannabis use. We report
      a "textbook example" of a 26-year-old man with CHS. CHS is an important
      differential diagnosis to consider in patients with similar symptoms and the
      distinctive symptom relief in hot water. Early recognition may prevent extensive,
      unnecessary medical examinations and frequent hospital admissions. 

PMID- 25394845
TI  - Let-7 microRNAs regenerate peripheral nerve regeneration by targeting nerve
      growth factor.
AB  - Peripheral nerve injury is a common clinical problem. Nerve growth factor (NGF)
      promotes peripheral nerve regeneration, but its clinical applications are limited
      by several constraints. In this study, we found that the time-dependent
      expression profiles of eight let-7 family members in the injured nerve after
      sciatic nerve injury were roughly similar to each other. Let-7 microRNAs (miRNAs)
      significantly reduced cell proliferation and migration of primary Schwann cells
      (SCs) by directly targeting NGF and suppressing its protein translation.
      Following sciatic nerve injury, the temporal change in let-7 miRNA expression was
      negatively correlated with that in NGF expression. Inhibition of let-7 miRNAs
      increased NGF secretion by primary cultured SCs and enhanced axonal outgrowth
      from a coculture of primary SCs and dorsal root gangalion neurons. In vivo tests
      indicated that let-7 inhibition promoted SCs migration and axon outgrowth within
      a regenerative microenvironment. In addition, the inhibitory effect of let-7
      miRNAs on SCs apoptosis might serve as an early stress response to nerve injury,
      but this effect seemed to be not mediated through a NGF-dependent pathway.
      Collectively, our results provide a new insight into let-7 miRNA regulation of
      peripheral nerve regeneration and suggest a potential therapy for repair of
      peripheral nerve injury. 

PMID- 25394846
TI  - Non-invasive indicators associated with the milk yield response after
      anthelmintic treatment at calving in dairy cows.
AB  - BACKGROUND: Gastrointestinal nematodes are an important cause of reduced
      performance in cattle. Previous studies in Europe showed that after anthelmintic
      treatment an average gain in milk production of around 1 kg per day/cow can be
      expected. However, (1) these studies have mainly evaluated group-based
      anthelmintic treatments during the grazing season or at housing and (2) little is
      known about parameters affecting variations in the treatment response amongst
      cows. A better knowledge of such parameters could help to select animals that
      benefit most from treatment and thus lead to a more rational use of
      anthelmintics. Therefore, a randomized, non-blinded, controlled clinical trial
      was performed on 11 commercial dairy farms (477 animals) in Belgium, aiming (1)
      to study the effect of eprinomectin treatment at calving on milk production and
      (2) to investigate whether the milk yield response was related to non-invasive
      animal parameters such that these could be used to inform targeted selective
      treatment decisions. RESULTS: Analyses show that eprinomectin treatment around
      calving resulted in an average (+/- standard error) increase of 0.97 (+/-0.41) kg
      in daily milk yield that was followed up over 274 days on average. Milk yield
      responses were higher in multiparous compared to primiparous cows and in cows
      with a high (4(th) quartile) anti-O. ostertagi antibody level in a milk sample
      from the previous lactation. Nonetheless, high responses were also seen in
      animals with a low (1(st) quartile) anti-O. ostertagi antibody level. In
      addition, positive treatment responses were associated with higher faecal egg
      counts and a moderate body condition score at calving (2(nd) quartile).
      CONCLUSIONS: In conclusion, this study provides novel insights into the
      production response after anthelmintic treatment at calving and factors which
      influence this. The data could be used to support the development of evidence
      based targeted selective anthelmintic treatment strategies in dairy cattle.

PMID- 25394847
TI  - Comparative effectiveness of Di'ao Xin Xue Kang capsule and Compound Danshen
      tablet in patients with symptomatic chronic stable angina.
AB  - A high proportion of patients with stable angina remains symptomatic despite
      multiple treatment options. Di'ao Xinxuekang (XXK) capsule and Compound Danshen
      (CDS) tablet have been approved for treating angina pectoris for more than 20
      years in China. We compare the anti-anginal effectiveness of XXK capsule and CDS
      tablet in patients with symptomatic chronic stable angina. A randomized,
      multicenter, double-blind, parallel-group, superiority trial was conducted in 4
      study sites. 733 patients with symptomatic chronic stable angina were included in
      the full analysis set. The primary outcomes were the proportion of patients who
      were angina-free and the proportion of patients with normal electrocardiogram
      (ECG) recordings during 20 weeks treatment. Compared with CDS, XXK significantly
      increased the proportion of angina-free patients, but no significant difference
      was noted in the proportion of patients with normal ECG recordings. Weekly angina
      frequency and nitroglycerin use were significantly reduced with XXK versus CDS at
      week 20. Moreover, XXK also improved the quality of life of angina patients as
      measured by the SAQ score and Xueyu Zheng (a type of TCM syndrome) score. We
      demonstrate that XXK capsule is more effective for attenuating anginal symptoms
      and improving quality of life in patients with symptomatic chronic stable angina,
      compared with CDS tablet. 

PMID- 25394848
TI  - Metabolism of the taxanes including nab-paclitaxel.
AB  - INTRODUCTION: The classical taxanes (paclitaxel, docetaxel), the newer taxane
      cabazitaxel and the nanoparticle-bound nab-paclitaxel are among the most widely
      used anticancer drugs. Despite years of research, the optimal dosing regimen
      (weekly vs 3-weekly) and optimal dose is still controversial, as is the value of
      pharmacological personalization of taxane dosing. AREAS COVERED: This review
      provides an overview of the pharmacological properties of the taxanes, including
      metabolism, pharmacokinetics-pharmacodynamics and aspects in the clinical use of
      taxanes. The latter includes the ongoing debate on the most active and safe
      regimen (paclitaxel, docetaxel, nab-paclitaxel), the recommended initial dose
      (cabazitaxel) and pharmacological dosing individualization. EXPERT OPINION:
      Taxanes share the characteristics of extensive hepatic metabolism and biliary
      excretion, the need for dose adaptation in patients with liver dysfunction, and
      substantial pharmacokinetic variability even after taking into account known
      covariates. Data from clinical studies suggest that optimal scheduling of the
      taxanes is dependent not only on the specific taxane compound, but also on the
      tumor type and line of treatment. Finally, treating oncologists should be aware
      of the substantial risk for drug-drug interactions that is a direct consequence
      of the complex hepatic metabolism of the taxanes.

PMID- 25394849
TI  - Socioeconomic inequality and caries: a systematic review and meta-analysis.
AB  - Dental caries is the most prevalent disease worldwide, with the majority of
      caries lesions being concentrated in few, often disadvantaged social groups. We
      aimed to systematically assess current evidence for the association between
      socioeconomic position (SEP) and caries. We included studies investigating the
      association between social position (determined by own or parental educational or
      occupational background, or income) and caries prevalence, experience, or
      incidence. Risk of bias was assessed using the Newcastle-Ottawa Scale for
      observational studies. Reported differences between the lowest and highest SEP
      were assessed and data not missing at random imputed. Random-effects inverse
      generic meta-analyses were performed, and subgroup and meta-regression analyses
      were used to control for possible confounding. Publication bias was assessed via
      funnel plot analysis and the Egger test. From 5539 screened records, 155 studies
      with mostly low or moderate quality evaluating a total of 329,798 individuals
      were included. Studies used various designs, SEP measures, and outcome
      parameters. Eighty-three studies found at least one measure of caries to be
      significantly higher in low-SEP compared with high-SEP individuals, while only 3
      studies found the opposite. The odds of having any caries lesions or caries
      experience (decayed missing filled teeth [DMFT]/dmft > 0) were significantly
      greater in those with low own or parental educational or occupational background
      or income (between odds ratio [95% confidence interval] = 1.21 [1.03-1.41] and
      1.48 [1.34-1.63]. The association between low educational background and having
      DMFT/dmft > 0 was significantly increased in highly developed countries (R (2) =
      1.32 [0.53-2.13]. Publication bias was present but did not significantly affect
      our estimates. Due to risk of bias in included studies, the available evidence
      was graded as low or very low. Low SEP is associated with a higher risk of having
      caries lesions or experience. This association might be stronger in developed
      countries. Established diagnostic and treatment concepts might not account for
      the unequal distribution of caries (registered with PROSPERO [CRD42013005947]). 

PMID- 25394850
TI  - Acetylsalicylic acid treatment improves differentiation and immunomodulation of
      SHED.
AB  - Stem cells from exfoliated deciduous teeth (SHED) possess multipotent
      differentiation and immunomodulatory properties. They have been used for
      orofacial bone regeneration and autoimmune disease treatment. In this study, we
      show that acetylsalicylic acid (ASA) treatment is able to significantly improve
      SHED-mediated osteogenic differentiation and immunomodulation. Mechanistically,
      ASA treatment upregulates the telomerase reverse transcriptase (TERT)/Wnt/beta
      catenin cascade, leading to improvement of SHED-mediated bone regeneration, and
      also upregulates TERT/FASL signaling, leading to improvement of SHED-mediated T
      cell apoptosis and ameliorating disease phenotypes in dextran sodium sulfate
      induced colitis mice. These data indicate that ASA treatment is a practical
      approach to improving SHED-based cell therapy. 

PMID- 25394851
TI  - Perceval Sutureless Valve - are Sutureless Valves Here?
AB  - With the advent of transcatheter aortic valve implantation (TAVI) techniques, a
      renewed interest has developed in sutureless aortic valve concepts in the last
      decade. The main feature of sutureless aortic valve implantation is the speed of
      insertion, thus making implantation easier for the surgeon. As a result, cross
      clamp times and myocardial ischemia may be reduced. The combined procedures (CABG
      with AVR in particular) can be done with a short cross clamp time. Perceval valve
      also provides an increased effective orifice area as compared with a stented
      bioprosthesis. Sutureless implantation of the Perceval valve is not only
      associated with shorter cross-clamp and cardiopulmonary bypass times but improved
      clinical outcomes too. This review covers the sutureless aortic valves and their
      evolution, with elaborate details on Perceval S valve in particular (which is the
      most widely used sutureless valve around the globe). 

PMID- 25394852
TI  - Glycolysis inhibitor 2-deoxy-D-glucose suppresses carcinogen-induced rat
      hepatocarcinogenesis by restricting cancer cell metabolism.
AB  - The abnormal metabolism of cancer cells is a crucial feature of tumors and
      provides promising therapeutic targets for cancer treatments. Aerobic glycolysis
      in cancer cells, termed the Warburg effect, is a highlighted characteristic of
      cancer-specific metabolism. However, the effect of glycolysis inhibition on
      hepatocarcinogenesis remains to be elucidated. In the present study, the effects
      of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) on the N-diethylnitrosamine
      (DEN)-induced rat hepatocarcinoma model and its underlying mechanisms were
      investigated. It was observed that 2-DG significantly delayed
      hepatocarcinogenesis and effectively prolonged survival time in the DEN-treated
      rats. The glycolysis inhibitor, 2-DG prominently decreased cell proliferation and
      increased cell apoptosis in the DEN-induced rat hepatoma and had no evident
      impact on the pericarcinomatous liver tissues. Further investigation revealed
      that 2-DG resulted in a reduction of glycolysis products, the compensatory
      increase of hexokinase 2 expression and a decrease in 6-phosphofructo-2-kinase,
      pyruvate kinase M2 and lactate dehydrogenase A expression in the hepatoma
      tissues. The inhibition of glycolysis further suppressed the tricarboxylic acid
      cycle, fatty acid and cholesterol biosynthesis and ATP production, while it
      promoted autophagic activation. In addition, the in vitro study demonstrated that
      hypoxia, an important factor in the tumor microenvironment, may assist in
      increasing 2-DG-induced inhibition of cell viability, cell cycle retardation and
      the decrease of colony formation ability in hepatoma cells. Taken together, the
      present results suggested that 2-DG may inhibit hepatocarcinogenesis in the DEN
      treated rats via restricting cancer cell metabolism. This finding provides a
      promising measure in the prevention and treatment of hepatoma.

PMID- 25394853
TI  - Burden of Illness in Hereditary Angioedema: A Conceptual Model.
AB  - The objective of the Hereditary Angioedema Burden of Illness Study in Europe was
      to assess the real-world experience of hereditary angioedema (HAE) from the
      patient perspective. Based on open-ended qualitative interviews with 30 patients
      from Spain, Germany and Denmark, 5 key themes emerged characterizing the impact
      of HAE on health-related quality of life (HRQoL): (i) unnecessary treatments and
      procedures, (ii) symptom triggers, (iii) attack impacts, (iv) caregiver impacts,
      and (v) long-term impacts. Patients for example experience unnecessary medical
      procedures due to diagnostic delays; anxiety and fear about attacks, and passing
      HAE to children; reduced work/school productivity; and limited career/educational
      achievement. Patient caregivers also experience worry and work/activity
      interruption during the attacks. In conclusion, a conceptual model was developed
      illustrating the hypothesized relationships among the wide-ranging short- and
      long-term HRQoL impacts of HAE. These findings can be used to highlight important
      issues in clinical management, raise awareness of the patients' experience among
      policymakers and help guide measurement of HRQoL outcomes in future studies in
      HAE.

PMID- 25394854
TI  - Effects of VBMDMP on the reversal of cisplatin resistance in human lung cancer
      A549/DDP cells.
AB  - Tumor drug resistance is a major obstacle to cancer chemotherapy. We previously
      constructed a fusion protein based on two tumstatin-derived sequences named
      recombinant VBMDM (rVBMDMP). We preliminarily confirmed its inhibition of HUVEC
      and colon cancer cell growth. The present study further systematically observed
      the inhibitory effect of rVBMDMP on lung cancer cell growth and analyzed a
      possible mechanism to provide a theoretical basis for the development of new
      antitumor protein drugs. The effect of rVBMDMP on human lung adenocarcinoma
      (A549) and cisplatin-resistant human lung adenocarcinoma (A549/DDP) cell
      proliferation was evaluated by MTS assay. Hoechst 33342 staining performed
      together with fluorescence microscopy and immunoblot analysis were used to
      examine the effects of rVBMDMP on the apoptosis of A549/DDP cells. A protein
      phosphorylation chip was used to identify changes in rVBMDMP-induced signaling
      protein phosphorylation. Changes in the phosphatidylinositol 3 kinase (PI3K)/Akt
      signal transduction pathway and expression of multidrug resistance protein (MRP
      2)-related molecules following rVBMDMP treatment in A549/DDP cells were evaluated
      by western blot analysis. A lung cancer xenograft model was used to evaluate the
      reversal effect of rVBMDMP on drug-resistance of A549/DDP cell tumors to
      cisplatin in vivo. The results demonstrated that rVBMDMP increased the
      phosphorylation of 79 signaling proteins, including focal adhesion kinase (FAK),
      caspase-6, Fas, FasL and FAF1 and downregulated 30 signaling proteins, including
      integrin alphaV, integrin beta3, PI3K/Akt, NF-kappaB and MRP-2 compared with the
      controls. rVBMDMP also increased the sensitivity of A549 and A549/DDP cells to
      cisplatin and directly induced apoptosis, which may be related to MRP-2 and Bcl-2
      downregulation. The effects of growth inhibition and apoptosis induction of
      rVBMDMP on A549/DDP cells may be related to the inhibition of integrin
      alphaVbeta3 and PI3K/Akt protein phosphorylation. Finally, we observed an
      increase in cancer cell sensitivity to cisplatin by rVBMDMP using the A549/DDP
      cell xenograft model in nude mice. Our study suggests that rVBMDMP may be an
      effective potential chemotherapy sensitizer and may be a viable drug candidate in
      anticancer therapies.

PMID- 25394856
TI  - Adjunctive glycine powder air-polishing for the treatment of peri-implant
      mucositis: an observational clinical trial.
AB  - OBJECTIVES: The aim of this study was to make a comparative evaluation of
      professional oral hygiene with or without the adjunct of glycine air-powder
      system for the treatment of peri-implant mucositis. METHODS: After the
      application of inclusion and exclusion criteria, patients were divided in two
      groups: in control group, patients were treated with professional oral hygiene
      manoeuvres (POH) while in the test group, glycine air-powder system (SGA) was
      adjuncted to professional oral hygiene. Probing depth (PD), bleeding index (BI)
      and plaque index (PI) were measured at baseline, and 3 and 6 months after the
      treatment. RESULTS: A total of 30 patients (15 per group) were selected for the
      study. In POH e SGA group, PD was, 2.86 +/- 0.37 and 3.00 +/- 0.36 mm at
      baseline, 2.90 +/- 0.53 and 2.62 +/- 0.50 mm after 3 months, 2.96 +/- 0.56 and
      2.41 +/- 0.54 mm after 6 months, respectively, significantly lower in SGA group
      in the last follow-up visit. In both groups, both PI and BI decreased over time.
      CONCLUSIONS: The present reports showed that both techniques were useful for the
      treatment of peri-implant mucositis. In the test group (with glycine powder), a
      significant reduction of probing depth was observed.

PMID- 25394855
TI  - The efficacy and safety of cilostazol in ischemic stroke patients with peripheral
      arterial disease (SPAD): protocol of a randomized, double-blind, placebo
      controlled multicenter trial.
AB  - RATIONALE: It is not uncommon for patients with ischemic stroke to have
      peripheral arterial disease (PAD). Patients with polyvascular diseases carry
      greater burden of atherosclerosis and higher risks of developing vascular events
      and death. More effective regimens, such as dual antiplatelet agents, may be more
      effective for controlling progression of atherosclerosis in secondary prevention.
      AIM: This study aims to evaluate whether cilostazol plus aspirin is more
      efficacious than aspirin alone for preventing progression of atherosclerosis in
      patients with ischemic stroke or transient ischemic attack (TIA) who also have
      peripheral arterial disease. DESIGN: The Safety and Efficacy of Cilostazol in
      Ischemic Stroke Patients with Peripheral Arterial Disease (SPAD) study is a
      randomized double-blinded placebo-controlled trial. Patients with previous
      ischemic stroke or TIA who had been taking aspirin (100 mg per day), aged 50
      years or older, with PAD in the lower limbs based on ankle-brachial index (ABI)
      <1.0 will be randomized into the treatment group with cilostazol (200 mg/day) or
      the placebo group on 1:1 basis. STUDY OUTCOMES: Patients will be evaluated at 1,
      3, 6, 9 and 12 months after randomization. The primary endpoint is difference in
      change in ABI between groups. The secondary and tertiary endpoints are the
      difference between groups in change in carotid intima-media thickness (IMT) and
      incidence rate of major cardiovascular events, including recurrent stroke,
      myocardial infarction, unstable angina, other vascular events, and death; and the
      safety measures, including major bleeding events, hemorrhagic stroke and death of
      any cause. CONCLUSION: The SPAD trial is the first study to evaluate the safety
      and efficacy of dual antiplatelet agents, aspirin plus cilostazol, in comparison
      with aspirin alone in patients with both ischemic stroke or TIA and PAD. Results
      from this trial will provide important information on the merit of adding
      cilostazol to aspirin for slowing down progression of atherosclerosis in patients
      with ischemic stroke and PAD.

PMID- 25394857
TI  - Linking ecosystem characteristics to final ecosystem services for public policy.
AB  - Governments worldwide are recognising ecosystem services as an approach to
      address sustainability challenges. Decision-makers need credible and legitimate
      measurements of ecosystem services to evaluate decisions for trade-offs to make
      wise choices. Managers lack these measurements because of a data gap linking
      ecosystem characteristics to final ecosystem services. The dominant method to
      address the data gap is benefit transfer using ecological data from one location
      to estimate ecosystem services at other locations with similar land cover.
      However, benefit transfer is only valid once the data gap is adequately resolved.
      Disciplinary frames separating ecology from economics and policy have resulted in
      confusion on concepts and methods preventing progress on the data gap. In this
      study, we present a 10-step approach to unify concepts, methods and data from the
      disparate disciplines to offer guidance on overcoming the data gap. We suggest:
      (1) estimate ecosystem characteristics using biophysical models, (2) identify
      final ecosystem services using endpoints and (3) connect them using ecological
      production functions to quantify biophysical trade-offs. The guidance is
      strategic for public policy because analysts need to be: (1) realistic when
      setting priorities, (2) attentive to timelines to acquire relevant data, given
      resources and (3) responsive to the needs of decision-makers. 

PMID- 25394859
TI  - Treatment considerations for MGMT-unmethylated glioblastoma.
AB  - Prognosis for patients with glioblastoma continues to be limited, despite an
      aggressive, multimodal treatment including alkylating chemotherapy. Temozolomide,
      the most widely used alkylating agent in glioblastoma, is cytotoxic to cells by
      inducing DNA damage but can be rapidly repaired by the protein O (6)
      methylguanine DNA methyltransferase (MGMT). In a subset of glioblastomas, the
      MGMT promoter is methylated, impairing the repair mechanism and conferring
      chemosensitivity. However, MGMT is overexpressed in 60 % of glioblastomas
      providing an inherent resistance to alkylating agents and challenging the role of
      temozolomide in this population. This article reviews the data establishing MGMT
      promoter methylation as a prognostic factor in glioblastoma and its potential
      role as a predictor of temozolomide response. It focuses on results from recent
      studies in newly diagnosed glioblastoma, and the role of temozolomide in MGMT
      unmethylated patients. We then turn the discussion to alternatives to
      temozolomide for newly diagnosed patients as well as therapeutic options at the
      time of recurrence.

PMID- 25394858
TI  - Nanotheragnostic applications for ischemic and hemorrhagic strokes: improved
      delivery for a better prognosis.
AB  - Stroke is the second leading cause of death worldwide and a major cause of long
      term severe disability representing a global health burden and one of the highly
      researched medical conditions. Nanostructured material synthesis and engineering
      have been recently developed and have been largely integrated into many fields
      including medicine. Recent studies have shown that nanoparticles might be a
      valuable tool in stroke. Different types, shapes, and sizes of nanoparticles have
      been used for molecular/biomarker profiling and imaging to help in early
      diagnosis and prevention of stroke and for drug/RNA delivery for improved
      treatment and neuroprotection. However, these promising applications have
      limitations, including cytotoxicity, which hindered their adoption into clinical
      use. Future research is warranted to fully develop and effectively and safely
      translate nanoparticles for stroke diagnosis and treatment into the clinic. This
      work will discuss the emerging role of nanotheragnostics in stroke diagnosis and
      treatment applications. 

PMID- 25394860
TI  - Identification of virulence associated loci in the emerging broad host range
      plant pathogen Pseudomonas fuscovaginae.
AB  - BACKGROUND: Pseudomonas fuscovaginae (Pfv) is an emerging plant pathogen of rice
      and also of other gramineae plants. It causes sheath brown rot disease in rice
      with symptoms that are characterized by brown lesions on the flag leaf sheath,
      grain discoloration and sterility. It was first isolated as a high altitude
      pathogen in Japan and has since been reported in several countries throughout the
      world. Pfv is a broad host range pathogen and very little is known about its
      virulence mechanisms. RESULTS: An in planta screen of 1000 random independent Tn5
      genomic mutants resulted in the isolation of nine mutants which showed altered
      virulence. Some of these isolates are mutated for functions which are known to be
      virulence associated factors in other phytopathogenic bacteria (eg. pil gene,
      phytotoxins and T6SS) and others might represent novel virulence loci.
      CONCLUSIONS: Being an emerging pathogen worldwide, the broad host range pathogen
      Pfv has not yet been studied for its virulence functions. The roles of the nine
      loci identified in the in planta screen are discussed in relation to
      pathogenicity of Pfv. In summary, this article reports a first study on the
      virulence of this pathogen involving in planta screening studies and suggests the
      presence of several virulence features with known and novel functions in the
      Pseudomonas group of bacteria.

PMID- 25394861
TI  - Candida albicans phospholipomannan: a sweet spot for controlling host
      response/inflammation.
AB  - Fungal cell walls contain several types of glycans, which play important roles in
      the pathogenesis of fungal infection and host immune response. Among them,
      glycosphingolipids have attracted much attention lately since they contribute
      actively to the fungi development and fungal-induced pathogenesis. Although
      glycosphingolipids are present in pathogenic and non-pathogenic fungi, pathogenic
      strains exhibit distinct glycan structures on their sphingolipids, which
      contribute to the regulatory processes engaged in inflammatory response. In
      Candida albicans, phospholipomannan (PLM) represents a prototype of these
      sphingolipids. Through its glycan and lipid moieties, PLM induces activation of
      host signaling pathways involved in the initial recognition of fungi, causing
      immune system disorder and persistent fungal disease. In this review, first we
      describe the general aspects of C. albicans sphingolipids synthesis with a
      special emphasize on PLM synthesis and its insertion into the cell wall. Then, we
      discuss the role of PLM glycosylation in regulating immune system activation and
      its contribution to the chronic persistent inflammation found in Candida
      infections and chronic inflammatory diseases. 

PMID- 25394862
TI  - Three-column osteotomies of the lower cervical and upper thoracic spine:
      comparison of early outcomes, radiographic parameters, and peri-operative
      complications in 48 patients.
AB  - PURPOSE: To evaluate and compare early radiographic and clinical outcomes of
      lower cervical and upper thoracic three-column osteotomies (3CO) for
      cervicothoracic kyphosis correction. METHODS: Patients who underwent 3CO at the
      cervicothoracic junction at two institutions were retrospectively reviewed.
      Patients were divided into two groups: lower cervical osteotomy (LCO) and upper
      thoracic osteotomy (UTO: T1-T5). Operative data, radiographic alignment, peri
      operative complications, and clinical outcomes were compared between the groups.
      RESULTS: Forty-eight patients [male: 24; female: 24; average age 61 years (range
      18-92 years); mean follow-up: 22 months] met inclusion criteria. A total of 24
      pedicle subtraction osteotomies and 24 vertebral column resections were
      performed. Compared to UTO, LCO operative time was significantly shorter, average
      ICU and hospital stays were significantly longer, and the average pre-operative
      cervical sagittal vertical axis (SVA) and kyphosis were significantly greater (p
      < 0.05). For both groups, there was significant improvement in cervical SVA,
      cervical lordosis, segmental angle, Neck Disability Index (NDI), SRS Activity,
      and pain visual analog score (p < 0.05). Reoperation rates were similar between
      the groups (LCO: 33.3 %; UTO: 18 %, p = 0.28). Significantly, more patients
      required tracheostomy/gastrostomy tubes after LCO (3 vs. 0 in the UTO group, p =
      0.03). CONCLUSIONS: Three-column posterior osteotomies at the cervicothoracic
      junction restored regional sagittal alignment and improved quality of life in
      this series of patients with rigid cervicothoracic deformity, albeit with high
      complication rates. Lower cervical osteotomies provided greater cervical SVA
      correction and were shorter operations, although they were associated with more
      complications and longer hospital and ICU stays compared to upper thoracic
      osteotomies.

PMID- 25394863
TI  - Selective colorectal cancer cell lysates enhance the immune function of mature
      dendritic cells in vitro.
AB  - The aim of the present study was to determine the most effective antigen with
      which to mature dendritic cells (DCs). The immune function of DCs loaded with
      lysates from three different colorectal cancer cell lines was compared. DCs were
      induced using granulocyte macrophage colony-stimulating factor, interleukin (IL)
      4 and tumor necrosis factor-alpha from the peripheral blood mononuclear cells of
      patients with colorectal cancer, and loaded with lysates from Colo320, SW480 and
      SW620 colorectal cancer cell lines, respectively. Autogenous T cells were co
      cultured with mature DCs. Surface markers and the secretory function of mature
      DCs and stimulated T cells were then analyzed. MTT assays were used to evaluate
      the killing capacity of autogenous cytotoxic T lymphocytes (CTLs). Compared with
      control, cluster of differentiation (CD)1a, CD83 and CD86, and human leukocyte
      antigen-DR expression levels were significantly higher in DCs matured using
      cancer cell lysates. In addition, IL-12 secretion levels were elevated.
      Autogenous T cells stimulated with DCs that were matured using cancer cell
      lysates showed a higher proliferation capacity, increased interferon-gamma
      secretion levels and stronger cytotoxic abilities compared with control cells.
      Among the three cell lines, SW480 lysates were most effective at promoting DC and
      T cell function. The results showed that SW480 lysates are more efficient than
      Colo320 and SW620 lysates in inducing DC immune function and activating the
      antitumor function of autogenous T cells.

PMID- 25394864
TI  - Connectivity cluster analysis for discovering discriminative subnetworks in
      schizophrenia.
AB  - In this manuscript, we present connectivity cluster analysis (CoCA), a novel
      computational framework that takes advantage of structure of the brain networks
      to magnify reproducible signals and quash noise. Resting state functional
      Magnetic Resonance Imaging (fMRI) data that is used in estimating functional
      brain networks is often noisy, leading to reduced power and inconsistent findings
      across independent studies. There is a need for techniques that can unearth
      signals in noisy datasets, while addressing redundancy in the functional
      connections that are used for testing association. CoCA is a data driven approach
      that addresses the problems of redundancy and noise by first finding groups of
      region pairs that behave in a cohesive way across the subjects. These cohesive
      sets of functional connections are further tested for association with the
      disease. CoCA is applied in the context of patients with schizophrenia, a
      disorder characterized as a disconnectivity syndrome. Our results suggest that
      CoCA can find reproducible sets of functional connections that behave cohesively.
      Applying this technique, we found that the connectivity clusters joining thalamus
      to parietal, temporal, and visuoparietal regions are highly discriminative of
      schizophrenia patients as well as reproducible using retest data and replicable
      in an independent confirmatory sample.

PMID- 25394865
TI  - The incidence of hip fractures in Norway -accuracy of the national Norwegian
      patient registry.
AB  - BACKGROUND: Hip fractures incur the greatest medical costs of any fracture. Valid
      epidemiological data are important to monitor for time-dependent changes. In
      Norway, hip fractures are registered in the Norwegian Patient Registry (NPR), but
      no published national validation exists. The aim of the present study was a
      national validation of NPR as a register for hip fractures using diagnostic codes
      (ICD-10 S 72.0-2) and/or procedure codes (NOMESCO version 1.14 NFBxy (x=0-9, y=0
      2) or NFJxy (x=0-9, y=0-2). METHOD: A nationwide, population-based cohort
      comprising a random sub-sample of 1,000 hip fracture-related entries for the
      years 2008-09 was drawn from the NPR. 200 entries were defined by a combination
      of diagnostic and procedure codes (subsample 1), 400 entries were defined by
      diagnostic codes only (subsample 2) and 400 entries were defined by procedure
      codes only (subsample 3). Accuracy was ascertained through comparison with
      discharge summaries, procedure notes and X-ray reports requested from 40 health
      institutions. Comparisons between groups were done by chi2 for categorical and t
      test for continuous variables. RESULTS: 792 health records from 32 institutions
      were reviewed. High accuracy (98.2%, 95% C.I. 96.5-99.9%) was found for subsample
      1, a combination of diagnostic and procedure codes. Coding errors were prominent
      in other subsamples. Defining fractures by a combination of diagnostic and
      procedure codes, annual average hip fracture incidence in Norway was 9,092 (95%
      C.I. 8,934 -9,249), excluding only 6.5% of all hip fractures defined by wider
      definitions. CONCLUSIONS: Based on current coding practice in Norway, a reliable
      national estimate of hip fracture incidences is found by a combination of
      relevant ICD-10 and NOMESCO codes in the NPR. This method may be used for
      monitoring epidemiological changes.

PMID- 25394869
TI  - Obesity: Adenosine protects from diet-induced obesity.

PMID- 25394870
TI  - Regulatory watch: Outcomes of EMA marketing authorization applications: does
      partnering have an influence?

PMID- 25394871
TI  - Metabolic disease: Mitochondrial uncoupler reverses diabetes.

PMID- 25394868
TI  - SCF ubiquitin ligase-targeted therapies.
AB  - The clinical successes of proteasome inhibitors for the treatment of cancer have
      highlighted the therapeutic potential of targeting this protein degradation
      system. However, proteasome inhibitors prevent the degradation of numerous
      proteins, which may cause adverse effects. Increased specificity could be
      achieved by inhibiting the components of the ubiquitin-proteasome system that
      target specific subsets of proteins for degradation. F-box proteins are the
      substrate-targeting subunits of SKP1-CUL1-F-box protein (SCF) ubiquitin ligase
      complexes. Through the degradation of a plethora of diverse substrates, SCF
      ubiquitin ligases control a multitude of processes at the cellular and organismal
      levels, and their dysregulation is implicated in many pathologies. SCF ubiquitin
      ligases are characterized by their high specificity for substrates, and these
      ligases therefore represent promising drug targets. However, the potential for
      therapeutic manipulation of SCF complexes remains an underdeveloped area. This
      Review explores and discusses potential strategies to target SCF-mediated
      biological processes to treat human diseases. 

PMID- 25394873
TI  - Trial watch: Self-inactivating gene-therapy vector alleviates safety concerns.

PMID- 25394875
TI  - Gender specific effects of neonatal limited nesting on viscerosomatic sensitivity
      and anxiety-like behavior in adult rats.
AB  - BACKGROUND: Evidence exists to suggest that early life stress (ELS), such as
      neglect or abuse has profound effects on the developing brain. The current study
      tests the hypothesis that ELS in the form of neonatal limited nesting (LN) may
      serve as a predisposing factor for the development of altered nociceptive
      processing and comorbid increases in anxiety-like behavior in adulthood. METHODS:
      Both male and female neonatal Sprague-Dawley rats were subjected to LN from
      postnatal day (PND) 2-9, while a control group was exposed to standard cage
      bedding. In adulthood, visceral sensitivity was assessed by quantifying a
      visceromotor behavioral response to graded isobaric pressures of colorectal
      distension. Hindpaw withdrawal thresholds in response to von Frey filaments were
      used to measure somatic sensitivity. Anxiety-like behavior was assessed in adult
      life using both the elevated plus maze and open field assay. KEY RESULTS: Early
      life stress in the form of neonatal LN induced visceral and somatic
      hypersensitivity in adult male rats and augmented anxiety-like behavior. However,
      in adult cycling females, neonatal LN did not alter nociceptive processing or
      lead to changes in the levels of anxiety-like behavior. CONCLUSIONS & INFERENCES:
      Our findings suggest that in male rats the LN model is a novel tool to
      investigate the long-term consequences of adverse early life experience on adult
      health.

PMID- 25394876
TI  - Patient height as a risk factor for poor outcome in acute type B aortic
      dissection.
AB  - BACKGROUND: Height has been shown in epidemiological studies to have mixed
      associations with long-term mortality. Shorter stature is related to higher all
      cause and coronary disease mortality, and taller stature is related to higher
      cancer and aortic aneurysm mortality. We evaluated height as a predictor of acute
      aortic dissection complexity and long-term mortality in a cohort of patients with
      acute type B aortic dissection. METHODS: Between February 2001 and January 2014
      we treated 461 acute type B aortic dissections. Median age was 60 years (range 16
      to 98). 175/461 (38%) were female, and 286 (62%) were male. Patients with
      uncomplicated dissection were managed medically, with blood pressure control and
      anti-impulse therapy as the main objectives. Patients with symptomatic
      malperfusion were managed by a variety of techniques, including open aortic
      surgical repair or stent grafting, branch vessel bypasses and flap fenestration
      as appropriate. Patients were followed with imaging and management of new
      symptoms. The upper quartile of height in our population (>180 cm) was considered
      tall for the analysis. RESULTS: Malperfusion or persistent symptoms were present
      in 154/461 (33.4%) patients at some time during the acute presentation. Presence
      of malperfusion-related complications was monotonically related to height, with
      complication rates of 23% in patients with height less than 165 cm, 31% in those
      with height between 166 and 173 cm, 39% at height between 173 and 180 cm, and 40%
      above 180 cm of height (P<0.02). Occurrence of complicated dissection was
      estimated to be nearly 50% at a height of 190 cm by logistic regression analysis.
      Independent predictors of long-term mortality were complication (Hazard Ratio-HR
      1.67, P<0.006), glomerular filtration rate (GFR) below 60 (HR 2.33, P<0.0001),
      and height >180 cm (HR 1.60, P<0.02). Five year survival estimates (adjusted for
      GFR and presence of complications) were 81% in the group with 180 cm or less in
      height and 63% in the group with height above 180 cm. CONCLUSIONS: Optimal
      management of acute type B aortic dissection is controversial. Identifying
      correlates of complicated acute dissection, such as height, could help to clarify
      the setting in which intervention is most appropriate. Height above 180 cm is an
      independent risk factor for long-term mortality, and should be considered in
      planning the management of acute type B aortic dissection.

PMID- 25394877
TI  - Eptifibatide infusion versus placebo in high risk patients with non-st segment
      elevation acute coronary syndromes managed with urgent coronary artery bypass
      graft surgery. a prospective multicenter randomized placebo-controlled clinical
      trial.
AB  - AIM: This randomized prospective clinical trial aimed to evaluate safety and
      efficacy of preoperative use of eptifibatide in high risk patients with non--ST-
      segment elevation acute coronary syndrome (NSTE--ACS), requiring urgent coronary
      artery bypass graft surgery (CABG). METHODS: A total of 140 patients with NSTE-
      ACS eligible for urgent surgical revascularization received either eptifibatide
      (bolus plus infusion) 12--48 hours prior to surgery (n=72 patients) or placebo
      (normal saline; n=68 patients) followed by routinely administered enoxaparin and
      aspirin. Patients were regarded as unsuitable for percutaneous coronary
      intervention by the heart team. CABG was performed 4 hours after discontinuation
      of eptifibatide or placebo infusion. The primary end point was major adverse
      cardiac and cerebrovascular events (MACCE) defined as death, nonfatal myocardial
      infarction (MI), stroke and the need for re--hospitalization due to recurrent
      ischaemia at 12 months follow--up. Secondary endpoints included MACCE rate at 1
      month, bleeding complications, platelet inhibition efficacy and correlation of
      platelet activity with MACCE rate. RESULTS: Cumulative one year MACCE rate was
      35% vs 14% in the control and treated group respectively (p=0.012). Mortality
      rate at 30 days follow--up was 10% vs 3% (p=0.021) and was not changed at 12
      months follow--up. There was a significant difference between both groups
      regarding perioperative MI (22% vs. 8%, p=0.03). The rates of stroke, blood loss
      and blood transfusion were similar in both groups. CONCLUSION: Preoperative use
      of eptifibatide vs. placebo is linked to significantly reduced 12--month MACCE
      rate in patients with NSTE--ACS requiring urgent CABG, while it simultaneously
      seems not to confer a greater risk of postoperative bleeding.

PMID- 25394878
TI  - Endovascular approaches to the ascending aorta for repair with straight and
      branched endografts: techniques and for what lesions.
AB  - Traditionally ascending aortic lesions have been repaired in open fashion:
      stenotomy, cardiopulmonary bypass, with or without deep hypothermic circulatory
      arrest. However, a subsegment of patients are deemed too high risk for open
      intervention. In the advent of endovascular advancement, this subset of patients
      may be treated with the use of stents (physician made, off-label use), branched
      stents, through a variety of methods and approaches. Although there are currently
      no large randomized, prospective studies, success has been seen in smaller case
      series. This review article addresses the identification of anatomy amenable to
      endovascular repair for management of type A aortic dissection, pseudoaneurysm,
      and zone 0 lesions. Different approaches to repair, including transapical,
      transeptal, femoral, common carotid, and axillary graft insertion are also
      examined. For endovascular treatment of ascending aortic lesions to grow as a
      field, devices made specifically for the ascending aorta need to be designed and
      larger trials are necessary to evaluate the rates of complications, morbidity,
      and mortality, and graft patency. 

PMID- 25394879
TI  - Organic/inorganic composite membranes based on poly(L-lactic-co-glycolic acid)
      and mesoporous silica for effective bone tissue engineering.
AB  - Fabrication of membranes with excellent biocompatibility and bioactivity remains
      an important technical challenge in bone tissue engineering. In this paper,
      poly(l-lactic-co-glycolic acid) (PLGA)-SBA15 (Santa Barbara Amorphous 15)
      composite membranes were prepared by using an electrospinning technique; PLGA was
      used as a biocompatible and biodegradable polymer and SBA15 was used as a
      mesoporous silica. The PLGA-SBA15 composite membrane facilitates the cell
      attachment and the cell proliferation versus pure PLGA membrane where human bone
      marrow-derived mesenchymal stem cells (hMSCs) were seeded. Furthermore, the
      analysis of alkaline phosphatase (ALP) activity indicated that this PLGA-SBA15
      composite membrane has better osteogenic induction compared with the pure PLGA
      membrane. Moreover, the presence of SBA15 increased the loading efficiency of the
      recombinant human bone morphogenetic protein-2 (rhBMP-2) to the membranes.
      Furthermore, the composite membrane had optimized sustained release of rhBMP-2.
      Overall, this PLGA-SBA15 composite is an excellent material for bone tissue
      engineering. 

PMID- 25394880
TI  - Coarse-grained modeling of peptidic/PDMS triblock morphology.
AB  - The morphology and chain packing structures in block copolymers strongly impact
      their mechanical response; therefore, to design and develop high performance
      materials that utilize block copolymers, it is imperative to have an
      understanding of their self-assembly behavior. In this research, we utilize
      coarse-grained (CG) molecular dynamics to study the effects of peptidic volume
      fraction and secondary structure on the morphological development and chain
      assembly of the triblocks poly(gamma-benzyl-L-glutamate)-b-poly(dimethylsiloxane)
      b-poly(gamma-benzyl-L-glutamate) (GSG) and poly(dimethylsiloxane)-b-poly(gamma
      benzyl-L-glutamate)-b-poly(dimethylsiloxane) (SGS). This necessitated developing
      a complete coarse-grained parameter set for poly(dimethylsiloxane) that closely
      captures the radial pair distribution of a united atom model and the experimental
      density at 300 K. These parameters are combined with the MARTINI amino acid CG
      force field and validated against prior reported values of domain spacing and
      peptide chain packing for GSG. The combined CG parameter set is then used to
      model SGS, a triblock currently in development for nature-inspired mechanically
      enhanced hybrid materials. The results reveal that the peptide side chain
      strongly influences the final morphology. For instance, lamellar or hexagonally
      packed cylindrical domain formation can result from the variation in side-chain
      interactions, namely, side-chain sterics preventing curved interface formation by
      increasing interfacial free volume. Ultimately, this research lays the foundation
      for future studies involving systems with dispersity, mixtures of secondary
      structures, and larger multiblock copolymers, such as polyurethanes and
      polyureas.

PMID- 25394881
TI  - Asymmetric hydrogenation of furans and benzofurans with iridium-pyridine
      phosphinite catalysts.
AB  - Enantioselective hydrogenation of furans and benzofurans remains a challenging
      task. We report the hydrogenation of 2- and 3-substituted furans by using iridium
      catalysts that bear bicyclic pyridine-phosphinite ligands. Excellent
      enantioselectivities and high conversions were obtained for monosubstituted
      furans with a 3-alkyl or 3-aryl group. Furans substituted at the 2-position and
      2,4-disubstituted furans proved to be more difficult substrates. The best results
      (80-97% conversion, 65-82% enantiomeric excess) were obtained with
      monosubstituted 2-alkylfurans and 2-[4-(trifluoromethyl)phenyl]furan. Benzofurans
      with an alkyl substituent at the 2- or 3-position also gave high conversions and
      enantioselectivity, whereas 2-aryl derivatives showed essentially no reactivity.
      The asymmetric hydrogenation of a 3-methylbenzofuran derivative was used as a key
      step in the formal total synthesis of the cytotoxic naphthoquinone natural
      product (-)-thespesone.

PMID- 25394882
TI  - The role of the posterior parietal cortex in stereopsis and hand-eye coordination
      during motor task behaviours.
AB  - The field of 'Neuroergonomics' has the potential to improve safety in high-risk
      operative environments through a better appreciation of the way in which the
      brain responds during human-tool interactions. This is especially relevant to
      minimally invasive surgery (MIS). Amongst the many challenges imposed on the
      surgeon by traditional MIS (laparoscopy), arguably the greatest is the loss of
      depth perception. Robotic MIS platforms, on the other hand, provide the surgeon
      with a magnified three-dimensional view of the environment, and as a result may
      offload a degree of the cognitive burden. The posterior parietal cortex (PPC)
      plays an integral role in human depth perception. Therefore, it can be
      hypothesized that differences in PPC activation between monoscopic and
      stereoscopic vision may be observed. In order to investigate this hypothesis, the
      current study explores disparities in PPC responses between monoscopic and
      stereoscopic visual perception to better de-couple the burden imposed by
      laparoscopy and robotic surgery on the operator's brain. Fourteen participants
      conducted tasks of depth perception and hand-eye coordination under both
      monoscopic and stereoscopic visual feedback. Cortical haemodynamic responses were
      monitored throughout using optical functional neuroimaging. Overall, recruitment
      of the bilateral superior parietal lobule was observed during both depth
      perception and hand-eye coordination tasks. This occurred contrary to our
      hypothesis, regardless of the mode of visual feedback. Operator technical
      performance was significantly different in two- and three-dimensional visual
      displays. These differences in technical performance do not appear to be
      explained by significant differences in parietal lobe processing. 

PMID- 25394883
TI  - Ready, set, go! Motivation and lifestyle habits in parents of children referred
      for obesity management.
AB  - BACKGROUND: Parents play a fundamental role in helping children with obesity to
      make and maintain healthy lifestyle changes. OBJECTIVE: This study aimed to
      characterize stages of engagement to change nutrition and physical activity
      habits among parents whose children with obesity were enrolled in obesity
      management and examine differences in parents' own nutrition and physical
      activity habits according to their stage of engagement. METHODS: Medical records
      of 113 children (body mass index [BMI] >=95th percentile) enrolled in an
      outpatient weight management clinic were reviewed for baseline (cross-sectional)
      data. Parents completed the Weight Loss Behavior-Stage of Change Scale to assess
      the degree of engagement in making healthy changes to their lifestyle behaviours.
      Latent class analysis was used to classify parents into distinct clusters by
      grouping individuals with similar ratings of stages of engagement regarding
      nutrition- and physical activity-related behaviours. RESULTS: Parents' engagement
      in healthy lifestyle behaviours varied (more engaged [n = 43]; less engaged [n =
      70]). A greater proportion of parents in the more engaged group was in action
      and/or maintenance stages of changing their lifestyle habits. The more engaged
      group was less overweight than the less engaged group (BMI = 28.5 vs. 33.3 kg m(
      2); P < 0.05). Further, the more engaged group consumed fewer total calories,
      calories from fat, trans fat and carbohydrates vs. their less engaged peers (P <
      0.05). Compared with the less engaged group, the more engaged group consumed more
      daily servings of vegetables and fruits (4.9 vs. 3.9, P < 0.05) and accumulated
      more steps per day (9130 vs. 7225; P < 0.05). The more engaged group was also
      more likely to meet daily recommendations for vegetable and fruit intake (48.8
      vs. 24.3%; P < 0.05) and physical activity (42.9 vs. 22.9%, P < 0.05).
      CONCLUSIONS: Parents of children with obesity varied in their degree of
      engagement in making healthy changes to their lifestyle behaviours, and those
      categorized as more engaged already demonstrated positive lifestyle behaviours.
      Information regarding parents' degree of engagement in healthy behaviours can
      inform clinical recommendations, especially when parents represent the primary
      agents of change in families trying to manage paediatric obesity.

PMID- 25394885
TI  - The effect of cathepsin K inhibitor on osteoclastic activity compared to
      alendronate and enamel matrix protein.
AB  - BACKGROUND/AIM: There have been several attempts to treat delayed replantation
      with agents that inhibit root resorption. The purpose of this study was to assess
      the effectiveness of cathepsin K inhibitor in inhibiting osteoclastic activity
      compared to that of alendronate and enamel matrix protein. MATERIALS AND METHODS:
      Murine RAW 264.7 cells were cultured in the presence of the receptor activator of
      NF-kB and lipopolysaccharide, followed by treatment with odanacatib, alendronate,
      or Emdogain at various concentrations. After drug treatment, an MTT assay was
      performed to evaluate cytotoxicity, while reverse transcription polymerase chain
      reaction and enzyme-linked immunosorbent assays were performed to determine the
      expression levels of interleukin-1beta, interleukin-6, prostaglandin E2, and
      tumor necrosis factor-alpha. Data were analyzed by one-way anova and Tukey's post
      hoc test (P < 0.05). RESULTS: Of all tested agents, Emdogain resulted in the
      least cytotoxicity on RAW 264.7 cells, while 10(-9) M odanacatib had the largest
      suppressive effects on the expression levels of inflammatory cytokines.
      CONCLUSIONS: Odanacatib inhibits osteoclastic activity, showing the possibility
      as a treatment agent for delayed replantation of avulsed teeth.

PMID- 25394884
TI  - Glucose and metformin modulate human first trimester trophoblast function: a
      model and potential therapy for diabetes-associated uteroplacental insufficiency.
AB  - PROBLEM: Diabetes confers an increased risk of preeclampsia, but its pathogenic
      role in preeclampsia is poorly understood. The objective of this study was to
      elucidate the effects of excess glucose on trophoblast function and whether any
      changes could be reversed by metformin. METHOD OF STUDY: The human first
      trimester trophoblast cell line (Sw.71) was treated with glucose at 5, 10, 25,
      and 50 mm, in the presence and absence of metformin. Trophoblast migration was
      quantified and supernatant cytokine, chemokine, and angiogenic factors measured.
      RESULTS: Increasing concentrations of glucose significantly increased trophoblast
      secretion of the inflammatory cytokines/chemokines: IL-1beta, IL-6, IL-8, GRO
      alpha, RANTES, and G-CSF; significantly increased trophoblast secretion of the
      anti-angiogenic factors sFlt-1 and sEndoglin; and significantly decreased
      trophoblast migration. Excess glucose-induced trophoblast IL-1beta production was
      inhibited by disabling the Nalp3/ASC inflammasome. Metformin partially reduced
      the glucose-induced inflammatory response, but had no effect on the anti
      angiogenic or antimigratory response. CONCLUSION: Excess glucose induced a pro
      inflammatory, anti-angiogenic, and antimigratory state in first trimester
      trophoblast cells. Glucose-induced trophoblast IL-1beta secretion was mediated by
      the inflammasome. Glucose-induced inflammation was partially reversed by
      metformin. These findings demonstrate the pleiotropic effects of hyperglycaemia
      on the trophoblast, providing potential explanations for the strong link between
      diabetes and preeclampsia.

PMID- 25394886
TI  - Lack of the serum- and glucocorticoid-inducible kinase SGK1 improves muscle force
      characteristics and attenuates fibrosis in dystrophic mdx mouse muscle.
AB  - Duchenne muscular dystrophy (DMD) is a human genetic disease characterized by
      fibrosis and severe muscle weakness. Currently, there is no effective treatment
      available to prevent progressive fibrosis in skeletal muscles. The serum- and
      glucocorticoid-inducible kinase SGK1 regulates a variety of physiological
      functions and participates in fibrosis stimulation. Here, we investigated whether
      SGK1 influences structure, function and/or fibrosis of the muscles from the mdx
      mouse, an animal model for DMD. As expected, mdx muscles showed the typical
      pathological features of muscular dystrophy including fiber size variations,
      central nuclei of muscle fibers, fibrosis in the diaphragm, and force reduction
      by 30-50 %. Muscles from sgk1 (-/-) mice were histologically overall intact and
      specific force was only slightly reduced compared to wild-type muscles.
      Surprisingly, soleus and diaphragm muscles of mdx/sgk1 (-/-) mice displayed
      forces close to wild-type levels. Most muscle fibers of the double mutants
      contained central nuclei, but fibrosis was not observed in any of the tested limb
      and diaphragm muscles. We conclude that the sole lack of SGK1 in mouse muscle
      does not lead to pronounced changes in muscle structure and function. However,
      dystrophin-deficient mdx muscle seems to benefit from SGK1 deficiency. SGK1
      appears to be an important enzyme in the process of fibrotic remodeling and
      subsequent weakness of dystrophin-deficient mouse muscle. 

PMID- 25394887
TI  - Treatment of symptomatic coral reef aorta with an uncovered stent graft.
AB  - Coral reef aorta is a rare condition characterised by extreme calcific growths
      affecting the juxta and suprarenal aorta. It can cause symptoms due to visceral
      ischaemia, lower limb hypoperfusion, and distal embolisation. We present a case
      of a 61-year-old man with unresponsive hypertension, who was found to have an
      occluded right renal artery, and an extensive coral reef aorta with a marked
      pressure gradient across the lesion. Renal hypoperfusion secondary to aortic
      coral reef aorta was thought to be the cause for his hypertension. Endovascular
      placement of a balloon expandable uncovered stent resolved his hypertension
      within one month, with no adverse effects noted at subsequent follow-up.
      Endovascular treatment of coral reef aorta is technically possible and avoids a
      major vascular procedure. 

PMID- 25394888
TI  - A rod-packing microporous hydrogen-bonded organic framework for highly selective
      separation of C2H2/CO2 at room temperature.
AB  - Self-assembly of a trigonal building subunit with diaminotriazines (DAT)
      functional groups leads to a unique rod-packing 3D microporous hydrogen-bonded
      organic framework (HOF-3). This material shows permanent porosity and
      demonstrates highly selective separation of C2H2/CO2 at ambient temperature and
      pressure.

PMID- 25394889
TI  - Major metropolis rail system access to dental care for the retired and elderly: a
      high-resolution geographic study of Sydney, Australia.
AB  - OBJECTIVE: This study examined the spatial accessibility of the Sydney Dental
      Hospital, to the people of metropolitan Sydney, using a geographic information
      systems approach. BACKGROUND: Sydney, Australia's largest city and the state
      capital of New South Wales, has 4.6 million people, with one-fifth of the
      Australian population (4.6 million people). Public dental services exist, but
      accessibility is limited to some specific population groups, who meet specific
      eligibility criteria. METHODS: All adults (those older than 15 years) were
      included in the study, and two subsets of this population, retirees (older than
      65 years) and elderly (older than 85 years), were also examined according to
      their proximity to the Sydney Dental Hospital, which is located immediately
      adjacent to the central train station. Census data (population data) and train
      station geo-coding data were integrated with high-resolution geographic
      information systems to analyse population spatial accessibility. RESULTS:
      Irrespective of the socioeconomic status, it was found that 43% of all the
      adults, 42.5% of the retirees and 41.6% of elders lived 2 km away from the
      nearest train station. Two-thirds of those in lower socioeconomic status lived
      within 2 km of a train station, whilst half of those in the higher socioeconomic
      status groups lived within 2 km from a train station. CONCLUSION: Metropolitan
      Sydney is an example of good urban planning where train stations are
      appropriately placed in high population density and low socioeconomic areas. The
      same should be investigated in other major metropolises, especially those still
      in growth and planning transportation systems.

PMID- 25394890
TI  - Distinct phenotype of hepatotoxicity associated with illicit use of anabolic
      androgenic steroids.
AB  - BACKGROUND: We have observed an increase in hepatotoxicity (DILI) reporting
      related to the use of anabolic androgenic steroids (AAS) for bodybuilding. AIM:
      To characterise phenotype presentation, outcome and severity of AAS DILI.
      METHODS: Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin
      American (5) DILI Registries were collated and compared with previously published
      cases. RESULTS: AAS DILI increased from representing less than 1% of the total
      cases in the Spanish DILI Registry in the period 2001-2009 to 8% in 2010-2013.
      Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury
      and jaundice were predominating features among the AAS cases. AAS DILI caused
      significantly higher bilirubin values independent of type of damage when compared
      to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases
      presented significantly higher mean peak bilirubin (P = 0.029) and serum
      creatinine values (P = 0.0002), compared to the hepatocellular cases. In a
      logistic regression model, the interaction between peak bilirubin values and
      cholestatic damage was associated with the development of AAS-induced acute
      kidney impairment (AKI) [OR 1.26 (95% CI: 1.035-1.526); P = 0.021], with 21.5
      *ULN being the best bilirubin cut-off point for predicting AKI risk (AUCROC
      0.92). No fatalities occurred. CONCLUSIONS: Illicit recreational AAS use is a
      growing cause of reported DILI that can lead to severe hepatic and renal injury.
      AAS DILI is associated with a distinct phenotype, characterised by considerable
      bilirubin elevations independent of type of damage. Although hepatocellular
      injury predominates, acute kidney injury develops in cholestatic cases with
      pronounced jaundice.

PMID- 25394891
TI  - The analysis of volatile organic compounds in exhaled breath and biomarkers in
      exhaled breath condensate in children - clinical tools or scientific toys?
AB  - Current monitoring strategies for respiratory diseases are mainly based on
      clinical features, lung function and imaging. As airway inflammation is the
      hallmark of many respiratory diseases in childhood, noninvasive methods to assess
      the presence and severity of airway inflammation might be helpful in both
      diagnosing and monitoring paediatric respiratory diseases. At present, the
      measurement of fractional exhaled nitric oxide is the only noninvasive method
      available to assess eosinophilic airway inflammation in clinical practice. We
      aimed to evaluate whether the analysis of volatile organic compounds (VOCs) in
      exhaled breath (EB) and biomarkers in exhaled breath condensate (EBC) is helpful
      in diagnosing and monitoring respiratory diseases in children. An extensive
      literature search was conducted in Medline, Embase and PubMed on the analysis and
      applications of VOCs in EB and EBC in children. We retrieved 1165 papers, of
      which nine contained original data on VOCs in EB and 84 on biomarkers in EBC.
      These were included in this review. We give an overview of the clinical
      applications in childhood and summarize the methodological issues. Several VOCs
      in EB and biomarkers in EBC have the potential to distinguish patients from
      healthy controls and to monitor treatment responses. Lack of standardization of
      collection methods and analysis techniques hampers the introduction in clinical
      practice. The measurement of metabolomic profiles may have important advantages
      over detecting single markers. There is a lack of longitudinal studies and
      external validation to reveal whether EB and EBC analysis have added value in the
      diagnostic process and follow-up of children with respiratory diseases. In
      conclusion, the use of VOCs in EB and biomarkers in EBC as markers of
      inflammatory airway diseases in children is still a research tool and not
      validated for clinical use. 

PMID- 25394892
TI  - A multicenter, prospective trial to evaluate mesh-augmented sacrospinous
      hysteropexy for uterovaginal prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: Hysterectomy is often part of pelvic organ prolapse
      repair. However, this may offer no benefit when compared to uterine preservation.
      We aimed to prospectively evaluate a minimally invasive bilateral sacrospinous
      hysteropexy using polypropylene mesh. We hypothesized that anatomic success and
      patient satisfaction can be achieved with this technique. METHODS: Women with
      uterovaginal prolapse desiring surgery who had completed childbearing were
      enrolled. Preoperative assessment included standardized prolapse examination and
      validated symptom and pain scale questionnaires. Women with prior pelvic organ
      prolapse repair or any contraindication to uterine preservation were excluded.
      Data including demographic, operative and postoperative information was collected
      on patients for 1 year following surgery. Continuous variables are summarized as
      means (standard deviation) and categorical variables are summarized as
      frequencies and percentages. A mixed-effects model was used to evaluate the
      changes in questionnaire scores and outcomes at 6 months and 12 months after
      surgery with random effects accounting for the center effect with adjustment for
      age. RESULTS: The study group comprised 99 women from three female pelvic
      medicine and reconstructive surgery (urogynecology) centers. The average age of
      the participants was 67.0 years (11.32 years), BMI 26.04 kg/m(2) (3.56 kg/m(2)),
      and the majority were multiparous (98.9%) and menopausal (90.9%). Overall success
      at 12 months, as measured by composite outcome was 97.7% (with the Ba point as
      the anatomic landmark) and 96.6% (with the C point as the anatomic landmark). The
      overall exposure rate was 6.52% and reoperation rate was 7.53%. All subjective
      questionnaire scores and anatomic outcomes had improved at 12 months.
      CONCLUSIONS: Sacrospinous hysteropexy using a minimally invasive polypropylene
      mesh kit is an effective and safe technique for addressing uterovaginal prolapse
      as an alternative to hysterectomy at the time of pelvic reconstructive surgery.

PMID- 25394893
TI  - Population norms for the EQ-5D index scores using Singapore preference weights.
AB  - PURPOSE: To provide norms for the EQ-5D index scores based on Singapore
      preference weights according to age, sex, ethnicity, and language version and
      compare the EQ-5D index scores for respondents with and without psychiatric
      disorders and chronic medical conditions. METHODS: The Singapore Mental Health
      Study was a cross-sectional epidemiological survey of a nationally representative
      sample of the resident (citizens and permanent residents) population in
      Singapore. The diagnoses of psychiatric disorders were established using the
      World Mental Health Composite International Diagnostic Interview version 3.0
      (CIDI 3.0). Index scores were derived using the Singapore preference weights.
      RESULTS: In general, the mean EQ-5D index score using Singapore preference
      weights decreased with increased age. The EQ-5D Malay version reported lower mean
      EQ-5D index than the English version. In multivariate analysis, the mean EQ-5D
      index for respondents with MDD, dysthymia, bipolar disorder, GAD, OCD, diabetes,
      hypertension, arthritis or rheumatism, neurological condition, stroke or major
      paralysis, heart attack, back problems, stomach ulcer, kidney failure, migraine
      headaches, and chronic lung disease was significantly lower than those without
      these conditions. CONCLUSIONS: These findings support the use of the Singapore
      preference weights for EQ-5D valuations when measuring health-related quality of
      life and comparing the health burden of psychiatric and chronic physical
      conditions among adults in Singapore.

PMID- 25394894
TI  - Support and negativity in interpersonal relationships impact caregivers' quality
      of life in pediatric food allergy.
AB  - PURPOSE: This study examined interpersonal relationship processes as they relate
      to health-related quality of life (HRQL) in caregivers of food-allergic children.
      Research questions explored the relative contributions of social support and
      social negativity to caregivers' adaptation as well as mechanisms of moderation,
      mediation, and moderated mediation through which these influences affect the
      association of time since children's food allergy diagnosis to caregivers' HRQL.
      METHODS: Caregivers (N = 299) of food-allergic children were recruited from
      parent groups associated with a food allergy nonprofit organization. Participants
      completed web-based questionnaires assessing demographics and child allergy
      characteristics, the extent of support and negativity experienced in their social
      relationships related caregiving, and their HRQL. Multiple regression analyses
      were used to examine relations among time since diagnosis, interpersonal
      relationship processes, and caregiver HRQL. RESULTS: Social negativity was
      directly related to diminished caregiver HRQL and was a stronger predictor of
      caregiver HRQL than social support. The effect of time since diagnosis on
      caregiver HRQL was indirect through social support, and this mediating effect did
      not depend on caregivers' experience of social negativity. CONCLUSIONS:
      Interpersonal relationship processes appear influential in the adaptation of
      caregivers in the context of pediatric food allergy. Psychosocial interventions
      targeting support and negativity in caregivers' social relationships may help
      improve their HRQL.

PMID- 25394895
TI  - Cross-cultural measurement equivalence of the EQ-5D-5L items for English-speaking
      Asians in Singapore.
AB  - PURPOSE: To investigate how the response labels of the 5-level EQ-5D (EQ-5D-5L)
      items are interpreted and used by English-speaking Chinese and non-Chinese
      Singaporeans, as a means to assessing whether those items are cross-culturally
      equivalent health-status measures in this Asian population. METHODS: In face-to
      face interviews, Chinese, Malay and Indian visitors to a primary care institution
      in Singapore were asked to rate the relative severity conveyed by EQ-5D-5L
      response labels, each containing the keyword of 'no(t),' 'slight(ly),'
      'moderate(ly),' 'severe(ly),' or 'unable'/'extreme(ly),' using a 0-100 numerical
      rating scale. Participants were also asked to describe 25 hypothetical health
      states using the EQ-5D-5L response labels. Differences between Chinese and
      Malay/Indian participants in label interpretation and selection were examined
      using multivariate regression analysis to adjust for participant characteristics.
      RESULTS: The differences in adjusted mean severity scores for individual EQ-5D-5L
      labels between Chinese (n = 148) and non-Chinese (Malay: n = 53; Indian: n = 56)
      participants ranged from 0.0 to 9.0. The relative severity of the labels to the
      participants supported the ordinality of the EQ-5D-5L response labels and was
      similar across ethnic groups. Chinese and non-Chinese participants selected
      similar response labels to describe each hypothetical health state, with the
      adjusted odds ratios of selecting any type of the five response labels for non
      Chinese versus Chinese participants ranging from 0.92 to 1.15 (p > 0.05 for all).
      CONCLUSIONS: The EQ-5D-5L items are likely to generate equivalent health outcomes
      between English-speaking Chinese and non-Chinese Singaporeans.

PMID- 25394896
TI  - Association between RECQL5 genetic polymorphisms and susceptibility to breast
      cancer.
AB  - Previous studies indicated that the RECQL5 gene polymorphism was associated with
      human cancers. However, the association of RECQL5 gene polymorphism with breast
      cancer remains unclear. In the present study, we investigated the association
      between polymorphisms of the RECQL gene and breast cancer in a Chinese
      population. We selected four polymorphisms of the RECQL5 gene (rs820186,
      rs820196, rs820200, and rs4789223) for the present study. The genotyping was
      performed using the TaqMan method in 510 patients with breast cancer and 510 age-
      and sex-matched non-cancer controls. We found that rs820196 and rs828200
      polymorphisms of RECQL5 were associated with breast cancer. For rs820196, the CC
      genotype (16.7 vs 9.4 %, P < 0.001) and C allele (42.5 vs 34.3 %, P < 0.001) were
      common in the breast cancer patients than in the control subjects, respectively.
      For rs828200, the GG genotype (23.7 vs 18.0 %, P < 0.001) and G allele (52.7 vs
      43.8 %, P < 0.001) were common in the breast cancer patients than in the control
      subjects, respectively. Haplotype analysis showed that C-G (odds ratio (OR) =
      2.247, 95 % confidence interval (CI) 1.854~2.722; P < 0.001) was associated with
      increased risk for breast cancer. However, the C-T (OR = 0.175, 95 % CI
      0.110~0.278; P < 0.001) and T-G (OR = 0.544; 95 % CI 0.428~0.692; P < 0.001) were
      associated with decreased risk for breast cancer, respectively. The present study
      indicated that the RECQL5 genetic polymorphism and haplotypes were associated
      with breast cancer in a Chinese population. 

PMID- 25394897
TI  - Targeting platelet-derived growth factor (PDGF) signaling in gastrointestinal
      cancers: preclinical and clinical considerations.
AB  - The prognosis of advanced gastrointestinal malignancies has been generally
      dreadful prompting robust search for better, more personalized, and more tailored
      treatments. In recent years, important signaling pathways leading to tumor
      progression and metastasis have been discovered with the subsequent development
      of targeted therapies to target these pathways. These include epidermal growth
      factor receptor (EGFR), vascular endothelial growth factor (VEGF), platelet
      derived growth factor (PDGF), mammalian target of rapamycin (mTOR), and
      mesenchymal epithelial transition (MET). In this review, we will revise the
      different biological and clinical aspects related to the use of PDGF pathway
      targeted therapies in gastrointestinal cancers with particular focus on the
      future prospective in that regard. 

PMID- 25394898
TI  - Tag SNPs of CFI contributed to the susceptibility for non-small cell lung cancer
      in Chinese population.
AB  - Complement factor I (CFI) plays an important role in the development of non-small
      cell lung cancer (NSCLC). This study aims to examine the association of CFI
      genetic variants with the risk of developing NSCLC in Chinese population. A
      hospital-based case-control study was conducted in 470 patients with NSCLC and
      470 controls in Chinese population. Totally, 13 tag single nucleotide
      polymorphisms (tag SNPs) of CFI were selected by Haploview software using the
      HapMap database. Genotyping was performed using iPLEX Gold Genotyping Assay and
      Sequenom MassARRAY. The odds ratios (ORs) and 95% confidence interval (95% CI)
      were calculated by logistic regression model. Our results showed that individuals
      with rs6822976 GG genotype had a significant decreased risk of NSCLC (OR = 0.64;
      95% CI = 0.42-0.98) when compared with rs6822976 AA genotype carriers. We also
      found that rs7671905 TT genotype exhibited a significant decreased risk of NSCLC
      compared with CC genotype with OR (95% CI) of 0.55 (0.33-0.91). There was no
      significant association between other selected SNPs and the risk of NSCLC. When
      stratified by smoking status, the decreased risk of NSCLC was observed to be
      associated with the genotype with at least one rs6822976 G allele among non
      smokers (OR = 0.66; 95% CI = 0.47-0.93), but not among smokers (OR = 1.01; 95% CI
      = 0.67-1.53). For CFI rs7671905 polymorphism, the individuals with at least one T
      allele have a decreased risk of NSCLC with OR (95 % CI) of 0.71 (0.51-0.99), but
      not among smokers (OR = 0.93; 95% CI = 0.61-1.41). When stratified by age, we
      found that rs7671905 TT genotype has contributed to the decreased risk of NSCLC
      among older subjects with OR (95% CI) of 0.46 (0.23-0.95), but not among younger
      subjects with OR (95% CI) of 0.64 (0.31-1.34) (P(interaction) = 0.03). After
      stratifying by sex, our study showed that rs7671905 TT genotype was related to
      the risk of NSCLC among males (OR = 0.53; 95% CI = 0.29-0.98), but not among
      females (OR = 0.62; 95% CI = 0.25-1.57) (P(interaction) = 0.03). CFI genetic
      variants played an important role in the development of NSCLC in Chinese
      population.

PMID- 25394899
TI  - Methylation of miR124a-1, miR124a-2, and miR124a-3 in Hodgkin lymphoma.
AB  - Deregulation of the microRNA miR124a by DNA methylation has been implicated in
      various malignancies, but no study reported its methylation status in Hodgkin
      lymphoma (HL). We evaluated the methylation of the three loci encoding for
      miR124a using methylation-specific PCR in 64 HL patients and 15 reactive lymph
      nodes obtained from patients with nonmalignant diseases. Results were correlated
      with clinicopathological parameters. Methylation rates of miR124a-1, miR124a-2,
      and miR124a-3 in HL were 17, 50, and 28%, respectively. None of the nontumoral
      samples showed aberrant hypermethylation in any of the miR tested. In HL cases,
      we found that miR124a-1 methylation correlates with high-risk International
      Prognostic Score (IPS) (score >3, p = 0.04) and that miR124a-2 methylation was
      more frequent in children (82.3%, p = 0.006) and men (63.9%, p = 0.01).
      Methylation of miR124a-3 was associated with advanced Ann-Arbor stages (p =
      0.007). The survival analysis showed that methylation of at least one of the
      miR124a genes was associated with shortened event-free survival in univariate (p
      = 0.03) and multivariate (p = 0.02) analyses. These results suggest that miR124a
      methylation is associated with aggressive HL disease and may be an interesting
      factor for predicting treatment response.

PMID- 25394900
TI  - MicroRNA-224 and its target CAMKK2 synergistically influence tumor progression
      and patient prognosis in prostate cancer.
AB  - We previously demonstrated that microRNA (miR)-224 expression was significantly
      reduced in human prostate cancer (PCa) tissues and predicted unfavorable
      prognosis in patients. However, the underlying mechanisms of miR-224 have not
      been fully elucidated. In this study, calcium/calmodulin-dependent protein kinase
      kinase 2 (CAMKK2) was identified as a target gene of miR-224. Then, we found that
      enforced expression of miR-224 could suppress PCa cell proliferation and cell
      cycle by regulating the expression of CAMKK2 in vitro. In addition, the
      expression levels of miR-224 in PCa tissues were negatively correlated with those
      of CAMKK2 mRNA significantly (Spearman's correlation: r = -0.66, P = 0.004).
      Moreover, combined low miR-224 expression and high CAMKK2 expression (miR-224
      low/CAMKK2-high) was closely correlated with advanced clinical stage (P = 0.028).
      Furthermore, PCa patients with miR-224-low/CAMKK2-high expression more frequently
      had shorter overall survival than those in groups with other expression patterns
      of two molecules. In conclusion, our data offer the convincing evidence that miR
      224 and its target gene CAMKK2 may synergistically contribute to the malignant
      progression of PCa. Combined detection of miR-224 and CAMKK2 expressions
      represents an efficient predictor of patient prognosis and may be a novel marker
      which can provide additional prognostic information in PCa.

PMID- 25394901
TI  - MiR-218 regulates cisplatin chemosensitivity in breast cancer by targeting BRCA1.
AB  - Cisplatin resistance presents a major challenge in the successful treatment of
      breast cancer, and its mechanism has not been documented well. In this study, to
      determine the relationship between chemotherapy resistance and microRNA (miRNA)
      expression during the development of cisplatin resistance in breast cancer, we
      used microRNA microarrays analysis successfully identified 19 miRNAs that were
      either overexpressed or underexpressed (8 upregulated and 11 downregulated) in
      the MCF-7 cell line and its cisplatin-resistant variant MCF-7/DDP. Among them,
      the miR-218 was most downregulated in cisplatin-resistant cell lines and
      identified that breast cancer 1 (BRCA1) was the cellular targets of miR-218. In
      vivo assay also demonstrated that restoring miR-218 expression in MCF-7/DDP cell
      line could sensitize cells against cisplatin, thereby increasing cisplatin
      mediated tumor cell apoptosis and reducing DNA repair. Kaplan-Meier survival
      analysis indicated that patients with breast cancer display high levels of miR
      218 and low levels of BRCA1 expression; these patients may gain the greatest
      benefits in terms of increased survival when treated with cisplatin. All of these
      results indicated that miR-218 has a significant function in the development of
      cisplatin resistance in breast cancer. Restoring miR-218 expression may
      constitute a novel therapeutic approach by which to increase cisplatin
      sensitivity in breast cancer. 

PMID- 25394903
TI  - The combination of agomelatine and ritanserin exerts a synergistic interaction in
      passive avoidance task.
AB  - Agomelatine is a potent agonist at melatonergic 1 and 2 (MT1 and MT2) receptors
      and an antagonist at serotonin-2C (5HT-2C) receptors. It was suggested that
      psychotropic effects of agomelatine is associated with its melatonergic and
      serotonergic effects. In this study, we aimed to evaluate the effects of
      agomelatine alone or in combination with ritanserin (5HT-2A/2C antagonist) on
      memory and learning. Male Balb-C mice (25-30 g) were used, and all drugs and
      saline were administrated by intraperitoneal (i.p.) route 30 min prior to
      evaluating retention time. Whilst agomelatine was administered at the doses of 1,
      10 and 30 mg/kg, ritanserin was administered at the doses of 0.1, 1 and 10 mg/kg.
      To evaluate memory function, passive avoidance test was used. On the first day,
      acquisition time and on the second day (after 24h), retention time of mice were
      recorded. To evaluate the synergistic activity, only the least doses of
      agomelatine and ritanserine were used, that is, 1 and 0.1 mg/kg, respectively.
      Scopolamine (1 mg/kg) was used as a reference drug, so it was combined with drug
      groups. Our results show that 5HT-2A/2C receptor antagonist ritanserin (1 and 4
      mg/kg, i.p.) and agomelatine (10 and 30 mg/kg, i.p.) improve memory deficit
      induced by scopolamine, whilst a synergistic interaction is observed between
      ritanserin and agomelatine (0.1 mg/kg and 1 mg/kg, i.p., respectively) when they
      were administered at their ineffective doses. According to our findings, we
      concluded that agomelatine improves memory deficit and thus improves the effect
      of agomelatine arises from its 5HT-2C receptor antagonist activity. 

PMID- 25394902
TI  - MiR-183/-96/-182 cluster is up-regulated in most breast cancers and increases
      cell proliferation and migration.
AB  - INTRODUCTION: The miR-183/-96/-182 cluster is a conserved polycistronic microRNA
      (miRNA) cluster which is highly expressed in most breast cancers. Although there
      are some sporadic reports which demonstrate the importance of each miRNA in this
      cluster in breast cancer, the biological roles of this cluster as a whole and its
      regulation mechanisms in breast cancer are still unclear. We compared the
      expression of this cluster in different cancer types, analyzed the regulation
      mechanism of this cluster, identified new target genes, and examined the impact
      of this cluster on breast cancer cells. METHODS: The miRNA level was detected by
      LNA-based northern blot and Real-time PCR, and was also analyzed from TCGA
      dataset. Bioinformatics research and luciferase assay were applied to find the
      promoter regions and transcription factors. To investigate the biological effects
      of the miR-183/-96 /-182 cluster in breast cancer, we generated miR-96, miR-182
      and miR-183 overexpression stable cell lines to check the overdose effects; we
      also used miR-DownTM antagomir for each miRNA as well as miR-183/-96 /-182
      cluster sponge lentivirus to check the knockdown effects. Growth, migration, cell
      cycle profile and survival of these cells was then monitored by colony formation
      assay, MTT assay, cell wound healing assay, flow cytometry and microscopy. The
      target gene was validated by Real-time PCR, luciferase assay, Western blot and
      Phalloidin/DAPI counterstaining. RESULTS: The miR-183/-96/-182 cluster was highly
      expressed in most breast cancers, and its transcription is disordered in breast
      cancer. The miR-183/-96/-182 cluster was transcribed in the same pri-miRNA and
      its transcription was regulated by ZEB1 and HSF2. It increased breast cell growth
      by promoting more rapid completion of mitosis, promoted cell migration and was
      essential for cell survival. MiR-183 targeted the RAB21 mRNA directly in breast
      cancer. CONCLUSION: The miR-183/-96/-182 cluster is up-regulated in most breast
      cancer. It functions as an oncogene in breast cancer as it increases cell
      proliferation and migration.

PMID- 25394904
TI  - Evolution of context dependent regulation by expansion of feast/famine regulatory
      proteins.
AB  - BACKGROUND: Expansion of transcription factors is believed to have played a
      crucial role in evolution of all organisms by enabling them to deal with dynamic
      environments and colonize new environments. We investigated how the expansion of
      the Feast/Famine Regulatory Protein (FFRP) or Lrp-like proteins into an eight
      member family in Halobacterium salinarum NRC-1 has aided in niche-adaptation of
      this archaeon to a complex and dynamically changing hypersaline environment.
      RESULTS: We mapped genome-wide binding locations for all eight FFRPs,
      investigated their preference for binding different effector molecules, and
      identified the contexts in which they act by analyzing transcriptional responses
      across 35 growth conditions that mimic different environmental and nutritional
      conditions this organism is likely to encounter in the wild. Integrative analysis
      of these data constructed an FFRP regulatory network with conditionally active
      states that reveal how interrelated variations in DNA-binding domains, effector
      molecule preferences, and binding sites in target gene promoters have tuned the
      functions of each FFRP to the environments in which they act. We demonstrate how
      conditional regulation of similar genes by two FFRPs, AsnC (an activator) and
      VNG1237C (a repressor), have striking environment-specific fitness consequences
      for oxidative stress management and growth, respectively. CONCLUSIONS: This study
      provides a systems perspective into the evolutionary process by which gene
      duplication within a transcription factor family contributes to environment
      specific adaptation of an organism.

PMID- 25394906
TI  - Profile of memory impairment as a prognostic marker in amnestic mild cognitive
      impairment.
AB  - We aimed to evaluate whether recognition memory can be used to identify patients
      with amnestic mild cognitive impairment (aMCI) at greater risk for converting to
      dementia. We recruited 2172 aMCI patients. They were divided into two groups:
      aMCI with impaired recall but normal recognition (aMCI-IRNR) vs aMCI with
      impaired recall and impaired recognition (aMCI-IRIR). We compared demographic
      findings and neuropsychological performance and illustrated the difference in
      converting to dementia between the two groups. Study subjects consisted of 1022
      (47.0%) patients with aMCI-IRNR and 1150 (53.0%) patients with aMCI-IRIR. In most
      neuropsychological tests except for digit span forward, patients with aMCI-IRIR
      were more impaired than patients with aMCI-IRNR even after adjustment of their
      age and sex. Cox analysis adjusting age and gender revealed that the risk of
      dementia conversion was higher in patients with aMCI-IRIR than in patients with
      aMCI-IRNR [hazard ratio (HR)=1.400, 95% CI 1.009-1.943; P=0.044]. This study
      showed that recognition memory can be used to identify patients with amnestic
      mild cognitive impairment (aMCI) at greater risk for converting to dementia.

PMID- 25394905
TI  - Histone H3.3 and its proteolytically processed form drive a cellular senescence
      programme.
AB  - The process of cellular senescence generates a repressive chromatin environment,
      however, the role of histone variants and histone proteolytic cleavage in
      senescence remains unclear. Here, using models of oncogene-induced and
      replicative senescence, we report novel histone H3 tail cleavage events mediated
      by the protease Cathepsin L. We find that cleaved forms of H3 are nucleosomal and
      the histone variant H3.3 is the preferred cleaved form of H3. Ectopic expression
      of H3.3 and its cleavage product (H3.3cs1), which lacks the first 21 amino acids
      of the H3 tail, is sufficient to induce senescence. Further, H3.3cs1 chromatin
      incorporation is mediated by the HUCA histone chaperone complex. Genome-wide
      transcriptional profiling revealed that H3.3cs1 facilitates transcriptional
      silencing of cell cycle regulators including RB/E2F target genes, likely via the
      permanent removal of H3K4me3. Collectively, our study identifies histone H3.3 and
      its proteolytically processed forms as key regulators of cellular senescence. 

PMID- 25394907
TI  - Helicobacter cinaedi meningitis: a case report and review of previous cases.

PMID- 25394908
TI  - Serial MR spectroscopy in hypertensive encephalopathy.

PMID- 25394909
TI  - Inhibition of the signal transducer and activator of transcription 3 signaling
      pathway by Qianliening capsules suppresses the growth and induces the apoptosis
      of human prostate cells.
AB  - The signal transducer and activator of transcription 3 (STAT3) pathway is one of
      the main growth factor-mediated signal transduction pathways and is closely
      associated with the occurrence and development of benign prostatic hyperplasia
      (BPH). Qianliening capsules (QC) have significant therapeutic effects on BPH;
      however, the precise mechanism underlying its anti-BPH activity remains to be
      elucidated. To further elucidate the molecular mechanism of the therapeutic
      effect of QC on BPH, the present study used epidermal growth factor (EGF), which
      has a role in the pathogenesis of BPH, to stimulate the growth of human prostate
      WPMY-1 cells and activate the STAT3 pathway in the WPMY-1 cells. The cell
      viability was determined using an MTT assay and the cell morphology was observed
      by phase-contrast microscopy. Fluorescence activated cell sorting analysis with
      Annexin-V/propidium iodide (PI) staining and PI staining were performed to
      examine cell apoptosis and the cell cycle. The activation of caspase-9 and -3
      were evaluated by colorimetric assay. STAT3 phosphorylation and transcriptional
      activity were detected by western blot analysis and the luciferase gene reporter,
      respectively. The mRNA and protein expression levels of B-cell lymhoma 2 (Bcl-2),
      Bcl-2-associated X protein (Bax), cyclin D1, cyclin-dependent kinase 4 (CDK4) and
      p21 were measured by reverse transcription quantitative polymerase chain reaction
      and western blot analysis, respectively. In the present study, QC was found to
      significantly and dose-dependently inhibit the EGF-stimulated growth of WPMY-1
      cells, as evidenced by QC-induced cell -morphological changes and a reduction in
      cell viability. In addition, QC treatment markedly induced the activation of
      caspase-9 and -3. QC treatment also inhibited the EGF-mediated increase of STAT3
      phosphorylation levels and transcriptional activity in WPMY-19 cells, accompanied
      by downregulation of the expression of Bcl-2, cyclin D1 and CDK4 and upregulation
      of the expression of Bax and p21. These results suggested that QC effectively
      inhibited the proliferation and promoted the apoptosis of human prostate cells
      via modulation of the STAT3 signaling pathway and its target genes, which is
      likely to be one of the mechanisms underlying its activity in BPH treatment.

PMID- 25394910
TI  - An introduced pentastomid parasite (Raillietiella frenata) infects native cane
      toads (Rhinella marina) in Panama.
AB  - The pentastomid parasite, Raillietiella frenata, is native to Asia where it
      infects the Asian House gecko, Hemidactylus frenatus. This gecko has been widely
      introduced and recently R. frenata was found in introduced populations of cane
      toads (Rhinella marina) in Australia, indicating a host-switch from introduced
      geckos to toads. Here we report non-native adult R. frenata infecting the lungs
      of native cane toads in Panama. Eight of 64 toads were infected (median = 2.5,
      range = 1-80 pentastomids/toad) and pentastomid prevalence was positively
      associated with the number of buildings at a site, though further sampling is
      needed to confirm this pattern. We postulate that this pattern is likely due to a
      host shift of this parasite from an urban-associated introduced gecko. This is
      the first record of this parasite infecting cane toads in their native range, and
      the first instance of this parasite occurring in Central America.

PMID- 25394911
TI  - Epileptic seizures as a manifestation of cow's milk allergy: a studied
      relationship and description of our pediatric experience.
AB  - Adverse reactions after ingestion of cow's milk proteins can occur at any age,
      from birth and even amongst exclusively breast-fed infants, although not all of
      these are hypersensitivity reactions. The most common presentations related to
      cow's milk protein allergy are skin reactions, failure to thrive, anaphylaxis as
      well as gastrointestinal and respiratory disorders. In addition, several cases of
      cow's milk protein allergy in the literature have documented neurological
      involvement, manifesting with convulsive seizures in children. This may be due to
      CNS spread of a peripheral inflammatory response. Furthermore, there is evidence
      that pro-inflammatory cytokines are responsible for disrupting the blood-brain
      barrier, causing focal CNS inflammation thereby triggering seizures, although
      further studies are needed to clarify the pathogenic relationship between atopy
      and its neurological manifestations. This review aims to analyze current
      published data on the link between cow's milk protein allergy and epileptic
      events, highlighting scientific evidence for any potential pathogenic mechanism
      and describing our clinical experience in pediatrics. 

PMID- 25394912
TI  - Clinician Perspectives on Delaying Initiation of Antiretroviral Therapy for
      Clinically Eligible HIV-Infected Patients.
AB  - OBJECTIVES: Guidelines for antiretroviral therapy (ART) initiation have evolved,
      but consistently note that adherence problems should be considered and addressed.
      Little is known regarding the reasons providers delay ART initiation in
      clinically eligible patients. METHODS: In 2009, we surveyed a probability sample
      of HIV care providers in 582 outpatient facilities in the United States and
      Puerto Rico with an open-ended question about nonclinical reasons for delaying
      ART initiation in otherwise clinically eligible patients. RESULTS: Very few
      providers (2%) reported never delaying ART. Reasons for delaying ART were
      concerns about patient adherence (68%), patient acceptance (60%), and structural
      barriers (33%). Provider and practice characteristics were associated with
      reasons for delaying ART. CONCLUSION: Reasons for delaying ART were consistent
      with clinical guidelines and were both patient level and structural. Providers
      may benefit from training and access to referrals for ancillary services to
      enhance their ability to monitor and address these issues with their patients.

PMID- 25394913
TI  - A likelihood ratio test for nested proportions.
AB  - For policy and medical issues, it is important to know if the proportion of an
      event changes after an intervention is administered. When the later proportion
      can only be calculated in a portion of the sample used to compute the previous
      proportion, the two proportions are nested. The motivating example for this work
      comes from the need to test whether admission rates in emergency departments are
      different between the first and a return visit. Here, subjects who contribute to
      the admission rate at the return visit must be included in the first rate and
      also return, but not vice versa. This conditionality means that existing methods,
      including the basic test of equality of two proportions, longitudinal data
      analysis methods, and recurrent event approaches are not directly applicable.
      Currently, researchers can only explore this question by the use of descriptive
      statistics. We propose a likelihood ratio test to compare two nested proportions
      by using the product of conditional probabilities. This test accommodates the
      conditionality, subject dependencies, and cluster effects and can be implemented
      in SAS PROC NLMIXED allowing for the proposed method to be readily used in an
      applied setting. Simulation studies showed that our approach provides unbiased
      estimates and reasonable power. Moreover, it generally outperforms the two-sample
      proportion z-test, in the presence of heterogeneity, and the Cochran-Mantel
      Haenszel test. An example based on readmission rates through an emergency
      department is used to illustrate the proposed method.

PMID- 25394914
TI  - Vertical forces assessment according to radiographic hip grade in German shepherd
      dogs.
AB  - OBJECTIVE: To investigate the correlation between radiographic hip grade and
      kinetic parameters in German shepherd dogs. METHODS: Dogs were distributed into
      five groups of eight dogs each according to hip grade (A, B, C, D or E). Dogs
      were submitted to clinical evaluation and kinetic analysis. Five valid passages
      were analysed using data collected from a pressure walkway. Peak vertical force,
      vertical impulse and stance phase duration were evaluated at velocity (1 . 2 to 1
      . 4 m/s) +/-0 . 1 m/s(2) acceleration. Kinetic data between groups were compared.
      RESULTS: In pelvic limbs, mean peak vertical force decreased progressively from
      grade C (mild) to grade E (severe) hip dysplasia. The vertical impulse was
      decreased in groups C and E compared to groups A, B and D; stance phase duration
      did not differ significantly between groups. CLINICAL SIGNIFICANCE: Mean peak
      vertical force was lower in dogs with severe hip dysplasia compared with mildly
      dysplastic dogs. These results suggest that hip dysplasia degree can affect
      lameness severity.

PMID- 25394915
TI  - Retraction: CCNs, fibulin-1C and S100A4 expression in leiomyoma and myometrium:
      inverse association with TGF-beta and regulation by TGF-beta in leiomyoma and
      myometrial smooth muscle cells.

PMID- 25394916
TI  - Retraction: The expression profile of micro-RNA in endometrium and endometriosis
      and the influence of ovarian steroids on their expression.

PMID- 25394917
TI  - A complicated case of metastatic thymoma.
AB  - This report describes the case of a 49-year-old man who presented to the hospice
      with severe neuropathic pain, cramps, muscle twitching, generalised sweating,
      insomnia and anxiety in the context of metastatic thymoma. The symptoms were
      exquisitely corticosteroid sensitive raising the possibility of an immunogenic
      aetiology. Morvan's syndrome, a paraneoplastic, immune-mediated syndrome
      characterised by peripheral nerve hyperexcitability, dysautonomia and central
      nervous system dysfunction was thus considered. Nerve conduction studies and
      electromyography were negative as were initial serological assays. Subsequent
      assays for antibodies to leucine-rich, glioma inactivated one protein and
      contactin-associated protein-2, recently discovered to be associated with
      Morvan's syndrome, confirmed the diagnosis. By the time the diagnosis of Morvan's
      syndrome was reached the patient was too unwell to receive disease-modifying
      treatments. An awareness of Morvan's syndrome in Palliative and Supportive care
      is essential to improve the outcome of patients with this devastating syndrome. 

PMID- 25394918
TI  - Increasing inpatient hospice use versus patient preferences in the USA: are
      patients able to die in the setting of their choice?
AB  - BACKGROUND: Growth in hospice utilisation has been accompanied by an increase in
      the proportion of hospice patients who die in an inpatient hospice setting rather
      than at home. OBJECTIVE: To determine whether this increase in inpatient
      utilisation is consistent with patient preferences. DESIGN: Retrospective cohort
      study. SETTING: Seven hospices in the Coalition of Hospices Organised to
      Investigate Comparative Effectiveness (CHOICE) network. PATIENTS: 70 488 patients
      admitted between 1 July 2008 and 31 May 2012. MEASUREMENTS: We measured changes
      in patients' stated preferences at the time of admission regarding site of death,
      including weights to adjust for non-response bias. We also assessed patients'
      actual site of death and concordance with patients' preferences. RESULTS: More
      patients died receiving inpatient care in 2012 as compared to 2008 (1920 (32.7%),
      2537 (18.5%); OR 1.21; 95% CI 1.19 to 1.22; p<0.001). However, patients also
      expressed an increasing preference for dying in inpatient settings (weighted
      preferences 27.5% in 2012 vs 7.9% in 2008; p<0.001). The overall proportion of
      patients who died in the setting of their choice (weighted preferences) increased
      from 74% in 2008 to 78% in 2012 (p<0.001). LIMITATIONS: This study included only
      seven hospices, and results may not be representative of the larger hospice
      population. CONCLUSIONS: Although more patients are dying while receiving
      inpatient care, these changes in site of death seem to reflect changing patient
      preferences. The net effect is that patients in this sample were more likely to
      die in the setting of their choice in 2012 than they were in 2008.

PMID- 25394919
TI  - Structural insight into the central element assembly of the synaptonemal complex.
AB  - The key step in meiosis is synaptonemal complex formation, which mediates
      homologous chromosome alignment and synapsis. False pairing between homologous
      chromosomes produces infertility. Here, we present a crystal structure of the
      mouse meiosis-specific protein SYCE3, which is a component of the synaptonemal
      complex central element. Our studies show that functional SYCE3 most likely forms
      a dimer or higher order oligomer in cells. Furthermore, we demonstrate that the
      SYCE3 N-helix interacts with the SYCE1 C-helix, which is another central element
      component. Our results suggest that helical packing may mediate intra- or inter
      association of each central element protein component, thereby playing an
      essential role in forming the synaptonemal complex central elements. 

PMID- 25394921
TI  - [Metastasis from breast cancer to the pituitary gland causing hyponatriaemia].
AB  - Breast cancer is the most common cancer in Danish women. Pituitary metastases are
      rare events. We report a 75-year-old woman with metastatic breast cancer who
      presented with pituitary insufficiency nine years after her initial cancer
      diagnosis. MRI of the pituitary region showed a parasellar mass and thickening of
      the infundibulum. Her condition progressed within months and deterioration of
      visual field and acuity developed. A transsphenoidal resection was performed to
      rescue her vision and pathology confirmed metastasis from a breast invasive
      ductal adenocarcinoma. 

PMID- 25394920
TI  - Scutellarein inhibits cancer cell metastasis in vitro and attenuates the
      development of fibrosarcoma in vivo.
AB  - Fibrosarcoma is an aggressive and highly metastatic cancer of the connective
      tissue, for which effective therapeutic methods are limited. Recently, there has
      been a renewed interest in small molecular compounds from natural products in the
      treatment of cancer. In the present study, we investigated the compound,
      scutellarein, extracted from the perennial herb Scutellaria lateriflora, and it
      was found to possess anticancer potential. Cell proliferation assay and cell
      cycle analysis revealed that the proliferation rate of HT1080 human fibrosarcoma
      cells was significantly suppressed by treatment with scutellarein through the
      induction of apoptosis. Moreover, an in vivo experiment using Balb/c nude mice
      revealed that the volume and weight of the tumors were markedly reduced following
      treatment with scutellarein. We also analyzed the effects of scutellarein on the
      markers of metastasis, using the HT1080 cells. The results indicated that
      scutellarein potently inhibited cell migration, invasion and the expression and
      activity of matrix metalloproteinase (MMP)-2, -9 and -14. Furthermore, MMP
      activation and cell survival were suppressed due to the scutellarein-mediated
      downregulation of nuclear factor kappa-light-chain-enhancer of activated B cells
      (NF-kappaB) activation. In conclusion, our data suggest that scutellarein has the
      ability to attenuate the development of fibrosarcoma and inhibit cancer cell
      metastasis.

PMID- 25394922
TI  - [Eclipse retinopathy].
AB  - Eclipse retinopathy is a condition with macular damage resulting from viewing of
      a solar eclipse. This case report illustrates how eclipse retinopathy was
      diagnosed with a delay of more than 30 years. The report also summarises how
      solar eclipse can be observed without risk of retinal damage. 

PMID- 25394923
TI  - [Subcutaneous atrophy following steroid injection in the treatment of trigger
      finger].
AB  - Trigger finger (TF), also known as stenosing tenosynovitis, is a rather common
      condition that causes entrapment of the flexor tendon at the site of the annular
      pulley. The accepted first-line treatment for TF is injection of long-acting
      corticosteroid in the involved flexor tendon sheath. This treatment is
      characterized by a high success rate and a low level of reported adverse effects
      in the literature. We report a case of subcutaneous atrophy after steroid
      injection in the treatment of TF. 

PMID- 25394924
TI  - [White matter alterations in schizophrenia].
AB  - Schizophrenia is a brain disorder characterized by fundamental changes in
      thinking and beliefs. Alterations in white matter integrity may underlie the
      characteristic psychotic symptoms. This review focuses on diffusion tensor
      imaging studies in schizophrenia patients. Overall, schizophrenia appears to be
      associated with white matter deficits particularly in the fronto-temporal
      connections. To dissect potential medication effects from myelination deficits
      related to symptoms, longitudinal studies in initially antipsychotic-naive first
      episode patients with schizophrenia are needed. 

PMID- 25394925
TI  - [Diagnosis and treatment of pancreatic cysts].
AB  - Incidental cystic lesions of the pancreas are often detected due to the increased
      use of cross-sectional imaging. Since mucinous cysts have a malignant potential,
      whereas pseudocysts and serous cystadenomas are benign, the distinction is of key
      clinical importance. Current recommendations advocate the use of multiple imaging
      modalities (CT/MRI/endoscopic US/endoscopic US & fine-needle aspiration) during
      evaluation and follow-up. This review describes the most frequent cystic lesions
      of the pancreas and suggests a simple investigation and treatment algorithm. 

PMID- 25394926
TI  - [Cholesterol crystals in synovial fluid in patients with rheumatoid arthritis may
      be linked with a poor prognosis].
AB  - We report two cases of cholesterol crystals (CC) in synovial fluid (SF) in
      patients with rheumatoid arthritis (RA). Injection of triamcinolone had
      satisfactory effect on the bursitis in one patient which is in contrast to
      previous reports. Both patients died short after presentation. There is evidence
      suggesting that RA synovium is more permeable to low-density lipoprotein and high
      density lipoprotein than healthy synovium. It has been hypothesised that the
      cholesterol lowering statins (HMG-CoA reductase inhibitors) might have an anti
      inflammatory effect in RA. 

PMID- 25394928
TI  - [In Process Citation].

PMID- 25394927
TI  - [MRI of the pineal gland].
AB  - The pineal gland (CP) is located centrally in the brain and produces melatonin.
      Cysts and concrements are frequent findings on MRI but their significance is
      still unclear. The visualization of CP is difficult due to its location and
      surrounding structures and so far, no standardized method exists. New studies
      suggest a correlation between CP-morphology and melatonin secretion as well as a
      connection between melatonin, disturbed circadian rhythm, and the development of
      cancer and cardiovascular diseases, underlining the need for a standardized
      approach to CP on MRI. 

PMID- 25394929
TI  - [The genome and the consumer].
AB  - Consumergenetics has developed so fast that it became possible for consumers to
      obtain genome risk information based on single nucleotide polymorphisms data of
      over 250 diseases/conditions for just 99 USD. In November 2013, the American Food
      and Drug Administration (FDA) ordered the company 23andMe to stop returning
      health results because they found a lack of scientific evidence of the reposted
      disease risks. The ethical dilemmas associated with this are reviewed, and the
      recommendations are described in genome testing. Ethical dilemmas in relation
      direct-to-consumer testing are discussed. 

PMID- 25394930
TI  - [Medical genetics and the genome].
AB  - Next generation sequencing, a remarkable progress in medical genetics, analyses
      the exome for disease-causing mutations (exome sequencing) especially in cases
      with genetic heterogeneity or cases where single gene approach has not revealed
      the diagnosis. Many unsolved questions exist such as unsolicited findings in
      genes not related to the patients' symptoms or variants of unknown significance.
      Informed consent is crucial before analysis but post-test genetic counselling and
      strategies for reporting back results to family members are necessary. 

PMID- 25394931
TI  - [The genome in terms of audiology and ophthalmology].
AB  - The article briefly reviews the impact of genetics and genomics in audiology and
      ophthalmology, respectively. The discovery of an increasing number of genes
      associated with hearing and visual impairment creates a foundation for a better
      understanding of pathophysiology, eventually leading to novel and more
      individualized treatments. Furthermore, genetic evaluation and counselling can
      contribute to molecular diagnosis, better prognostication, and mode of
      inheritance. Next generation sequencing is a technology well suited to dissect
      the vast genetic heterogeneity in these conditions. 

PMID- 25394932
TI  - [Genomics of mental disorders].
AB  - The heritability of mental disorders is high, but it has been very difficult to
      unravel the genetic architecture. In the past five years, unprecedented progress
      has been made on the insight of the genetic background of several mental
      disorders, and the present article describes the current results. The disorders
      are extremely polygenic with thousands of common as well as rare risk variants,
      some of which are shared across disorders. Epigenetic modifications and
      potentially gene-environment interactions are adding further complexity to the
      picture. 

PMID- 25394933
TI  - [The genome and cardiology].
AB  - Several cardiac diseases are autosomal dominantly inherited. This includes
      cardiomyopathies, primary arrhythmias (channelopathies), dyslipidaemias,
      premature ischaemic heart diseases and diseases of the thoracic aorta. Sudden
      cardiac death in the young is also often due to one of the inherited cardiac
      diseases. Clinical and genetic cascade family screening of the relatives to
      patients with inherited cardiac diseases is now organized in a national network
      of centres of cardiology, sharing pedigrees, clinical and genetic information.
      This gives unique opportunities for offering focused prophylaxis in the group of
      high-risk relatives. 

PMID- 25394934
TI  - [The genome and cancer treatment].
AB  - Basic research has uncovered the molecular pathogenesis of both sporadic and
      hereditary cancer and this has paved the way for the use of genome-wide
      technologies to depict the molecular drivers of individual tumours and for
      development of personalized and targeted treatment. This review describes the
      recent application of next generation sequencing and microarrays in the
      classification of cancers and the prospects of personalized medicine in oncology.

PMID- 25394935
TI  - [The genome and diabetes].
AB  - In terms of their genetic architecture monogenic diabetes and type 2 diabetes
      represent two extremes. Whereas each subtype of monogenic diabetes is caused by
      one penetrant, rare mutation in a single gene, the genetic susceptibility to type
      2 diabetes can be attributed to many low-penetrant variants across the genome. At
      present, only 10% of the genetic susceptibility to type 2 diabetes can be
      explained by the hitherto identified 90 genomic loci. Here we briefly review the
      genetics of monogenic diabetes and type 2 diabetes and outline future directions
      of research within this field. 

PMID- 25394936
TI  - [The genome and ageing].
AB  - Lifespan, longevity and healthy aging are complex phenotypes, and unravelling of
      the genetic background has been challeng-ing. Excess of advantageous gene
      variants seems to be of more importance for longevity than absence of known
      disease-sus-ceptibility genes. Animal studies have pointed to candidate path-
      ways related to ageing, but only a few genes have repeatedly been associated to
      human lifespan. Research into the genetic contribution to a long and healthy life
      is currently focusing on epigenetic phenomena and the importance of rare variants
      in families enriched for longevity. 

PMID- 25394937
TI  - [The genome and pharmacology].
AB  - Pharmacogenetics is the science about how germ line mutations affect the response
      to drugs, and the role of single nucleotide polymorphisms in cytochrome P450
      (CYP) genes has been particularly well studied during the last 25 years. The
      current knowledge about CYP2C9, VKORC1 and warfarin, CYP2C19 and clopidogrel,
      CYP2D6 and tamoxifen and CYP3A5 and tacrolimus is summarized, and it is concluded
      that genotyping before treatment seems to be of little practical use for all four
      drugs. The same applies to simvastatin and SLCOB1 and metformin and OCT1
      transporter polymorphisms. 

PMID- 25394938
TI  - The fungal pathogen Cryptococcus neoformans manipulates macrophage phagosome
      maturation.
AB  - Phagocytosis by cells of the innate immune system, such as macrophages, and the
      subsequent successful maturation of the phagosome, is key for the clearance of
      pathogens. The fungal pathogen Cryptococcus neoformans is known to overcome
      killing by host phagocytes and both replicate within these cells and also escape
      via a non-lytic process termed vomocytosis. Here we demonstrate that, during
      intracellular growth, cryptococci modify phagolysosome maturation. Live
      cryptococci, but not heat-killed pathogens or inert targets, induce the premature
      removal of the early phagosome markers Rab5 and Rab11. In addition, significant
      acidification of the phagosome, calcium flux and protease activity is hindered,
      thus rendering the phagosome permissive for cryptococcal proliferation.
      Interestingly, several attenuated cryptococcal mutants retain this ability to
      subvert phagosomal maturation, suggesting that hitherto unidentified pathogen
      mechanisms regulate this process.

PMID- 25394939
TI  - Diadenosine pentaphosphate modulates glomerular arteriolar tone and glomerular
      filtration rate.
AB  - INTRODUCTION: Mechanisms and participating substances involved in the reduction
      of glomerular filtration (GFR) in contrast-induced acute kidney injury (CI-AKI)
      are still matter of debate. We hypothesized that diadenosine polyphosphates are
      released by the action of contrast media on tubular cells and may act on
      glomerular arterioles and reduce GFR. METHODS: Freshly isolated rat tubules were
      treated with the contrast medium iodixanol (47 mg iodine per mL) at 37  degrees C
      for 20 min. The content of Apn A (n = 3-6) in the supernatant of treated tubules
      and in the plasma of healthy persons and patients with AKI was analysed using
      reversed-phase chromatography, affinity chromatography and mass spectrometry. GFR
      was obtained in conscious mice by inulin clearance. Concentration response curves
      for Apn A (n = 3-6, 10(-12) -10(-5)  mol L(-1) ) were measured in isolated
      perfused glomerular arterioles. RESULTS: Iodixanol treatment of tubules
      significantly increased the concentration of Apn A (n = 3-5) in the supernatant.
      Ap6 A was below the detection limit. AKI patient shows higher concentrations of
      Apn A compared to healthy. Application of Ap5 A significantly reduced the GFR in
      conscious mice. Ap5 A reduced afferent arteriolar diameters, but did not
      influence efferent arterioles. The constrictor effect on afferent arterioles was
      strong immediately after application, but weakened with time. Then, non-selective
      P2 inhibitor suramin blocked the Ap5 A-induced constriction. CONCLUSION: The data
      suggest that Ap5 A plays a role in the pathophysiology of CI-AKI. We show a
      contrast media-induced release of Ap5 A from tubules, which might increase
      afferent arteriolar resistance and reduce the GFR.

PMID- 25394940
TI  - Management of spondylolysis and low-grade spondylolisthesis in fine athletes. A
      comprehensive review.
AB  - OBJECTIVE: To provide evidence-based data about the aetiology, incidence,
      diagnosis and treatment of isthmic lumbar spondylolysis and low-grade
      spondylolisthesis and return to athletic activities in fine athlete. DESIGN: This
      is a comprehensive literature review. A thorough MEDLINE search in the period
      from 1973 to 2014 with the keywords: athlete, spondylolysis, low-grade
      spondylolisthesis, treatment and return to athletic activities was conducted.
      RESULTS: A total of 228 articles were initially enrolled from the search, and 74
      case series and reviews were finally included because they referred to incidence,
      diagnosis, treatment and return to play in fine athletes with symptomatic isthmic
      spondylolysis and low-grade (Meyerding I and II) spondylolisthesis. There were 13
      studies reporting surgical treatment (194 patients of average age 19 years) and
      14 studies with conservative treatment (589 patients of average age 15.7). The
      percentage of athletes who were successfully treated with conservative or
      operative treatment was 85 and 87.8%, respectively. CONCLUSION: Conservative
      treatment including physiotherapy and bracing is the mainstay in the treatment of
      symptomatic spondylolysis and low-grade isthmic spondylolisthesis in fine
      athletes. If consequent treatment fails, the operative treatment (pars repair and
      short fusion) is decided. Return to play following surgery varies from 6 to 12
      months with prohibition in collision sports. Return to play is mostly depended on
      specific sport activity.

PMID- 25394941
TI  - The safety and immunogenicity of a MF59-adjuvanted H5N1 prepandemic influenza
      vaccine in healthy adults primed with homologous or heterologous H5N1 vaccines:
      an observational study.
AB  - BACKGROUND: World Health Organization (WHO) has recommended individuals with
      increased risk of contracting influenza A H5N1 infection to be immunized against
      the virus during the inter-pandemic period. Safety and immunogenicity of H5N1
      vaccine among participants primed with homologous or heterologous H5N1 vaccines
      produced by diverse manufactures have not been reported. METHODS: Healthy
      individuals aged 20 to 60 years old were recruited and stratified into three
      groups: participants without priming (control group), participants primed with
      A/Indonesia/05/2005 vaccine, participants primed with A/Vietnam/1194/2004 vaccine
      and A/Indonesia/05/2005 vaccine. Enrolled participants received two doses of MF59
      adjuvanted A/Vietnam/1194/2004 vaccine (study vaccine). Solicited reactions were
      recorded by vaccine recipients. Blood samples were obtained for hemagglutination
      inhibition test. RESULTS: A total of 131 participants were enrolled. No
      significant adverse events were recorded. Tenderness, fatigue and general muscle
      ache were the most common solicited reactions which alleviated within one week of
      immunization. Three weeks after two doses of the study vaccine, 63%, 68% and 88%
      were in seroprotective status in the control group, A/Indonesia/05/2005 primed
      group and A/Vietnam/1194/2004 and A/Indonesia/05/2005 primed group, respectively.
      Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 showed high
      immune response after booster with one dose of the study vaccine. CONCLUSION: The
      study vaccine did not cause severe adverse events. It elicited mostly mild to
      moderate reactions among participants. Participants primed with
      A/Vietnam/1194/2004 and A/Indonesia/05/2005 vaccine showed higher immune response
      than those without priming or primed with A/Indonesia/05/2005 vaccine. The report
      suggested those with an increased risk of influenza A H5N1 virus exposure may
      benefit from receiving influenza A H5N1 priming during the inter-pandemic period
      if the antigenicity of the pandemic influenza strain is similar to that of the
      priming strain.

PMID- 25394943
TI  - Cell death: breaking down memory.

PMID- 25394942
TI  - Complement--tapping into new sites and effector systems.
AB  - Complement is traditionally known to be a system of serum proteins that provide
      protection against pathogens through direct cell lysis and the mobilization of
      innate and adaptive immunity. However, recent work indicates that the complement
      system has additional physiological roles beyond those in host defence. In this
      Opinion article, we describe the new modes and locations of complement activation
      that enable it to interact with other cell effector systems, such as growth
      factor receptors, inflammasomes and metabolic pathways. We propose that the
      location of complement activation dictates its function.

PMID- 25394944
TI  - Mucosal immunology: sick of the flu.

PMID- 25394945
TI  - Infectious disease: the tolerance of superspreaders.

PMID- 25394946
TI  - Tumour immunology: anticancer drugs copy bugs.

PMID- 25394947
TI  - Autoimmunity: troublemaker T cells target ribosomal protein.

PMID- 25394948
TI  - Impact of COMT Val158Met-polymorphism on appetitive conditioning and
      amygdala/prefrontal effective connectivity.
AB  - Appetitive conditioning is an important mechanism for the development,
      maintenance, and treatment of psychiatric disorders like substance abuse.
      Therefore, it is important to identify genetic variations, which impact
      appetitive conditioning. It has been suggested that the Val(158) Met-polymorphism
      in the Catechol-O-Methyl-Transferase (COMT) is associated with the alteration of
      neural processes of appetitive conditioning due to the central role of the
      dopaminergic system in reward processing. However, no study has so far
      investigated the relationship between variations in the COMT Val(158) Met
      polymorphism and appetitive conditioning. In this fMRI study, an appetitive
      conditioning paradigm was applied, in which one neutral stimulus (CS+) predicted
      appetitive stimuli (UCS) while a second neutral stimulus (CS-) was never paired
      with the UCS. As a main result, we observed a significant association between the
      COMT Val(158) Met-genotype and appetitive conditioning: skin conductance
      responses (SCRs) revealed a significant difference between CS+ and CS- in Val/Val
      allele carriers but not in the other genotype groups. Val/Val-allele carriers
      showed increased hemodynamic responses in the amygdala compared with the Met/Met
      allele group in the contrast CS+ > CS-. In addition, psychophysiological
      interaction analysis revealed increased effective amygdala/ventromedial
      prefrontal cortex connectivity in Met/Met-allele carriers. The increased amygdala
      activity points to facilitated appetitive conditioning in Val/Val-allele carriers
      while the amygdala/prefrontal connectivity results could be regarded as a marker
      for altered emotion regulation during conditioning, which potentially impacts
      appetitive learning sensitivity. The SCRs finding indicates a stronger
      conditioned response in the Val/Val-allele group and dovetails with the neural
      differences between the groups. These findings contribute to the current research
      on COMT in emotional processing.

PMID- 25394949
TI  - Prehabilitation for men undergoing radical prostatectomy: a multi-centre, pilot
      randomized controlled trial.
AB  - BACKGROUND: An emerging field of research describes the role of preoperative
      health behaviours, known as prehabilitation. The preoperative period may be a
      more physically and emotionally salient time to introduce and foster chronic
      adherence to health behaviours, such as exercise, in patients compared to post
      treatment during recovery. Moreover, physical and psychosocial improvements
      during the preoperative period may translate into an enhanced recovery trajectory
      with reduced operative complications and postoperative adverse effects. No
      studies have assessed prehabilitation for men with prostate cancer undergoing
      radical prostatectomy. METHODS/DESIGN: This is a multi-centre, pilot randomized
      control trial conducted at two Canadian urban teaching hospitals. 100 men
      undergoing radical prostatectomy for prostate cancer with no contraindications to
      exercise will be recruited and randomized to the prehabiliation program or usual
      care. Prehabilitation participants will engage in a preoperative, individualized
      exercise program including pelvic floor muscle strengthening instructions and a
      healthy lifestyle guide for men with prostate cancer. These participants will be
      asked to engage in 60 minutes of home-based, unsupervised, moderate-intensity
      exercise on 3-4 days per week. Usual care participants will receive the same
      pelvic floor muscle strengthening instructions and healthy lifestyle guide only.
      We will assess the feasibility of conducting an adequately powered trial of the
      same design via recruitment rate, programmatic adherence/contamination,
      attrition, and safety. Estimates of intervention efficacy will be captured
      through measurements at baseline (4-8 weeks preoperatively), within 1 week prior
      to surgery, and postoperatively at 4, 12, and 26 weeks. Efficacy outcomes
      include: fatigue, quality of life, urinary incontinence, physical fitness, body
      composition, aerobic fitness, pain, and physical activity volume. DISCUSSION: The
      primary outcome of this study is to determine the feasibility of conducting a
      full-scale, randomized controlled trial of prehabilitation versus usual care and
      to estimate effect sizes that will inform sample size determinations for
      subsequent trials in this field. To our knowledge, this is the first study to
      examine a structured presurgical exercise program for men undergoing radical
      prostatectomy for prostate cancer. This trial will advance our understanding of
      strategies to efficiently and effectively use the preoperative period to optimize
      postoperative recovery. TRIAL REGISTRATION: Clinicaltrials.gov Identifier:
      NCT02036684.

PMID- 25394950
TI  - mRNA expression of glucocorticoid receptor and serological and virological
      markers of chronic hepatitis B.
AB  - Glucocorticoid receptor (GR) function is essential for glucocorticoid action on
      various effector cells. The aim of the present study was to investigate the mRNA
      expression profiles of GRalpha and GRbeta in peripheral blood mononuclear cells
      (PBMC) and examine the association between the expression levels of the GR
      isoforms and the serological and virological hepatitis B virus (HBV) status in
      patients with chronic hepatitis B (CHB). A total of 29 CHB patients were examined
      in the present study, which were divided into subgroups according to serological
      and virological markers. The levels of GRalpha and GRbeta in PBMCs, HBV viral
      loads, HBV surface antigen (HBsAg), HBV e antigen (HBeAg) and pre-S1Ag were
      measured. A total of 43 healthy individuals served as controls. GRalpha was
      present in the PBMCs of all CHB patients and healthy controls, whereas GRbeta
      specific products were present in only 93.1% of the CHB patients and 86.0% of the
      healthy controls. The GRalpha levels were positively correlated with the
      expression of GRbeta in the CHB patients (r=0.419; P<0.05) and were significantly
      lower compared with those observed in the healthy controls (60.51 +/- 23.73, vs.
      100.00 +/- 40.75; P<0.001). Compared with the healthy controls, significant
      differences were observed in the mRNA expression of GRalpha in the CHB patients
      when stratified according to the HBeAg, pre-S1Ag and HBV viral load status
      (P<0.05), but not in the pre-S1Ag-positive patients. These data demonstrated that
      the mRNA expression profile of GRalpha differed between the CHB patients and the
      healthy controls. In addition, the HBV serological and virological markers were
      not associated with the mRNA levels of the GR isoforms in the CHB patients.

PMID- 25394951
TI  - Food access and children's BMI in Toronto, Ontario: assessing how the food
      environment relates to overweight and obesity.
AB  - OBJECTIVES: The objective was to examine how access to fast food restaurants,
      less healthy/healthier food outlets and supermarkets relate to measured levels of
      overweight and obesity among grade 5 and 6 students. METHODS: Measured height and
      weight data were obtained to measure BMI. The location and type of food outlet
      were derived from Toronto Public Health. The density of fast food, less
      healthy/healthy food outlets and supermarkets within a 1-km walk of the child's
      home was calculated along with the distance to the closest. Logistic regression
      models examined the relationship between food access and overweight/obesity.
      RESULTS: Lower income residents were more likely to be overweight or obese, as
      were boys. Living in an area with a higher density of healthy food outlets and in
      close proximity to a supermarket decreased the odds of being overweight or obese.
      CONCLUSIONS: Addressing several limitations in the literature, the findings
      confirm an association between the food retail environment and body weight.
      Density of healthy food outlets and distance to the nearest supermarket are
      important factors to be considered in addressing the childhood obesity pandemic.

PMID- 25394952
TI  - Homocysteine as a risk factor of restenosis after carotid endarterectomy.
AB  - AIM: Homocysteine (Hcy) has been identified as a potential risk factor for
      vascular disease. This study investigates the role of serum Hcy as clinical risk
      factor for restenosis after carotid endarterectomy (CEA). METHODS: In a
      prospective design, we studied patients who underwent carotid endarterectomy with
      venous patch closure technique with respect to alterations of Hcy levels pre and
      postoperatively. The patients studied were subjected to reevaluation for possible
      restenosis at time-points 3, 6, 9, 12, 18 and 24 months postoperatively. RESULTS:
      Fifty-three symptomatic and 37 asymptomatic patients with stenosis of internal
      carotid artery >70% were studied. Restenosis appeared in 7.25% of the patients
      within 24 months postoperatively. Hcy was the only parameter that correlated
      significantly with the presence of restenosis (P=0.010) and the presence of type
      VI (complicated) atheromatous plaque (P=0.005) within 24 months postoperatively.
      CONCLUSION: Hcy levels were found to be statistically significantly correlated
      with both the presence of complicated atheromatous plaque and the degree of
      internal carotid artery restenosis after CEA.

PMID- 25394953
TI  - The rate of aortic arch branching variation in Chinese patients using multislice
      spiral computed tomography angiography.
AB  - AIM: The aim of this study was to study the frequency of aortic arch branching
      variation in Chinese patients using multislice spiral computed tomography (MSCT)
      angiography. METHODS: Retrospectively analysis of MSCT images from 750
      consecutively enrolled patients to study the frequency of aortic arch branching
      variation. RESULTS: Among 750 patients enrolled, 21 cases were excluded due to
      poor image quality, and a total of 729 cases were included for the analysis. Nine
      types of aortic arch branching pattern were identified. The aortic arch branch
      has absented of any variation (type I) in 559 patients (76.68%). The most
      frequent anatomical variant was the common origin to the right brachiocephalic
      trunk and left common carotid artery (type II), which occurred in 97 patients
      (13.31%). From type III to type IX, the incidence rate of variation was 2.61%,
      5.76%, 0.14%, 0.82%, 0.27%, 0.27% and 0.14%, respectively. CONCLUSION: This is
      the largest study to date that investigated the frequency of aortic arch
      branching variation in Chinese patients using MSCT. The study showed that the
      rate of type V aortic arch variation is different between Chinese patienst and
      Westerners ones. Also, this study identified one case of aortic arch branching
      variant (type IX) that has not been reported before. MSCT can depict the blood
      vessel variation from multilayer and multi-angle, reveal its structural
      relationship with surrounding tissue, and guide the clinical diagnosis and
      treatment.

PMID- 25394954
TI  - Cognitive function in patients with peripheral artery disease: a prospective
      single-center cohort study.
AB  - AIM: The aim of the present study was to examine the association between
      cardiovascular comorbidities and risk factors, and cognitive function in
      peripheral artery disease (PAD) patients, as well as to determine the influence
      of cognitive function on cardiovascular outcome in a two-year follow-up. METHODS:
      The cognitive function of 104 PAD patients was assessed using the mini-mental
      test (MMSE). Ankle Brachial Index (ABI), Fontaine stage, PAD localization,
      cardiovascular risk factors and comorbidities were taken from the electronic
      patient charts. A multiple logistic regression model, which included myocardial
      infarction (MI), stroke/transient ischemic attack (TIA), diabetes mellitus (DM),
      coronary heart disease (CHD) and smoking was performed to compare patients with
      and without cognitive impairment. All study participants were followed for two
      years in order to evaluate their cardiovascular outcome, mortality and
      revascularisation rate. RESULTS: There was no significant difference in mini
      mental state between asymptomatic and symptomatic PAD patients. ABI and PAD
      localization was not related to cognitive function. However, pre-existing stroke,
      TIA, coronary artery disease (CAD) or DM were associated with a lower MMSE score.
      When MMSE was dichotomized in <=27 and >27 points, the presence of CAD, history
      of cerebrovascular events and DM was associated with a MMSE <=27 in multivariate
      analysis. There was no association between MMSE and cardiovascular event rate.
      CONCLUSION: PAD patients with CAD, stroke, TIA or DM have worse cognitive
      function than those without these factors. There was no evidence that cognitve
      function influenced cardiovascular outcome.

PMID- 25394955
TI  - Elevated endocan levels and its association with clinical severity in Stevens
      Johnson Syndrome and toxic epidermal necrolysis.
AB  - AIM: The aim of this study was to determine the levels of endocan and other
      biomarkers of inflammation in the systemic circulation of three groups of
      patients: 1) biopsy confirmed Stevens Johnson Syndrome, Toxic Epidermal
      Necrolysis (SJS/TEN) subjects; 2) patients with allergic skin reactions but
      biopsy negative for SJS/TEN; and 3) normal controls. Besides, this paper aims to
      investigate the association of endocan levels with the extent of the skin
      lesions, the presence of purpura, and the degree of acute renal insufficiency, as
      well as to investigate endocan as a marker of clinical severity by correlating
      endocan levels with the SCORTEN results (a prognositic score for SJS/TEN).
      METHODS: Sixteen patients over the age of 18 years who were referred to Loyola
      University Medical Center with severe allergic skin reactions were recruited over
      a two-year period from May 2012 to May 2014. A diagnosis of SJS or TEN was
      confirmed in 7 subjects by skin biopsy. Citrated plasma samples were assayed for
      endocan, tumor necrosis factor-alpha (TNFalpha), vascular endothelial growth
      factor (VEGF), and C-reactive protein (CRP). The differences between SJS/TEN
      subjects, biopsy negative subjects, and normal controls (N.=23) were explored
      using ANOVA and Tukey's post-hoc test. Associations with other clinical variables
      were identified using linear and logistic regression. RESULTS: Biopsy positive
      SJS/TEN subjects and biopsy negative subjects had higher endocan levels than
      normal controls (SJS/TEN: 3.01 ng/mL [IQR: 2.15-8.11]; biopsy negative: 3.96
      ng/mL [IQR: 1.54-4.85]; normal controls: 1.79 ng/mL [IQR: 1.67-1.98]; ANOVA
      P=0.0038). Endocan levels were more strongly associated with SCORTEN in SJS/TEN
      subjects than in biopsy negative subjects (R2 SJS/TEN=0.5110; biopsy
      negative=0.0317). SJS/TEN subjects exhibited significantly higher levels of TNF
      alpha compared to normal controls (P=0.0267). The TNF-alpha levels were
      significantly lower compared to biopsy negative subjects (P=0.0052). VEGF levels
      were also elevated among SJS/TEN and biopsy negative subjects compared to normal
      controls (SJS/TEN: 12.04 pg/mL: [IQR: 7.64-52.7]; biopsy negative: 10.54 pg/mL
      [IQR: 4.17-6.46]; normal controls: 4.94 pg/mL [IQR: 4.17-6.46]; ANOVA P<0.0001).
      There was no significant difference in VEGF levels between SJS/TEN and biopsy
      negative subjects (P=0.7110). Similarly, CRP levels were elevated among SJS/TEN
      patients and biopsy negative subjects compared to normal controls (SJS/TEN: 32.09
      ug/mL [IQR: 31.49-52.08]; biopsy negative: 83.38 ug/mL [IQR: 44.74-145.38];
      healthy normal: 1.08 ug/mL [IQR: 0.73-2.03]; ANOVA P<0.0001). There was no
      significant difference in CRP levels between SJS/TEN and biopsy negative subjects
      (P=0.2416). CONCLUSION: To our knowledge, this is the first study to evaluate
      enodcan, a marker of endothelial dysfunction, in the systemic circulation of
      SJS/TEN patients. Elevated endocan levels were more strongly associated with
      disease severity among SJS/TEN subjects than among less severe allergic reactions
      with skin involvement.

PMID- 25394956
TI  - Cold climate could be an etiologic factor involved in Raynaud's phenomenon
      physiopathology. Epidemiological investigation from 954 consultations in general
      practic.
AB  - AIM: The physiopathology of Raynaud's phenomenon (RP) is not currently fully
      resolved. The cold seems to be not only an important factor triggering attacks,
      but also inducing RP. The aims of this study were to assess the prevalence of RP
      in Nantes urban district, and study the relationship between RP prevalence and
      cold climate. METHODS: Patients aged between 10 and 80 years old, consulting in
      five Nantes General Practices, from June 2011 and March 2012, were included.
      Patients presenting RP underwent a full clinical examination. Subjects not
      meeting Allen and Brown criteria benefited from at least a dosage of Anti-Nuclear
      Antibodies and a naifold Capillaroscopy. Climate data provided by French national
      weather agency allowed establishing an average of observed temperatures during
      the past five years and correlating them to the observed prevalence. RESULTS: Of
      954 patients included, 78 had a RP, for an overall prevalence estimated at 8.2%.
      The prevalence among women (8.9%) was slightly higher than men (7.3%). Secondary
      form represented 5.1% of RP. In the RP group, 13 patients were active smokers,
      mean BMI was 22.3+/-3.2 kg/m2, and only 4 patients were treated by
      vasoconstrictor therapy. According to French national weather agency, between
      2007 and 2011, mean temperature of January in Nantes area was 5.8  degrees C.
      CONCLUSION: We confirmed that the lower winter temperatures a region experiences,
      the higher the prevalence of RP, thus raising the question of the
      physiopathological role of the cold in the induction or in the revelation of RP.

PMID- 25394957
TI  - Chronic traumatic thoracic aortic aneurysms-results of endovascular treatment.
      Fourteen-year single-center experience.
AB  - AIM: Chronic traumatic thoracic aneurysms are results of blunt trauma of the
      chest during motorcar accident. Treatment of choice is the endovascular procedure
      with stent-graft. METHODS: Between 2000-2012 in General and Thoracic Surgery
      Department 30 patients with post-traumatic aneurysms were operated. In all cases
      aneurysm was located below left subclavian artery and in 63% developed during
      road traffic accident. RESULTS: All patients were operated on with 100% technical
      success and no device failure was noticed. None of patients died during the
      endovascular procedure and no serious complications like spinal cord ischemia was
      observed. In one (3%) case, where left subclavian artery was covered, stroke was
      diagnosed treated conservatively. CONCLUSION: At long-term follow-up, one
      endoleak type IA was found, solved with balloon-plasty. Two patients died due to
      cardiac diseases.

PMID- 25394958
TI  - Impact of Duplex arterial mapping on decision making in non-acute ischemic limb
      patients.
AB  - AIM: The aim of this study was to demonstrate the impact of Duplex arterial
      mapping on decision making in non-acute ischemic limb patient group reporting
      pain onset between 15 days and 3 months. METHODS: We prospectively evaluated
      patients presented with critical limb ischemia who reported pain onset of
      duration between 15 days and 3 months in one-year period. Our series included
      thirty cases (mean age=61.3 years old), as Duplex arterial mapping was the sole
      preoperative imaging tool performed in all of them. All patients, in whom duplex
      indicated thrombosis in long occluded segments, were candidates for
      fluoroscopically guided thrombectomy. When Duplex defined chronic arterial
      occlusions, patients underwent endovascular or bypass revascularisation
      procedures. Impact of Duplex wall interrogation on decision-making between the
      two groups (subacute and chronic) was measured. RESULTS: Duplex arterial mapping
      categorized correctly all 30 patients into either subacute ischemia with
      removable clot (N.=14) or chronic ischemia (N.=16). Fluoroscopic guided
      thrombectomy was performed in 14 cases when Duplex advised long occluded arterial
      segments as indicted by intact intima with echogenic thrombus inside. Bypass
      surgery was performed in 8 patients. Percutaneous transluminal angioplasty (PTA)
      was done in 7 cases and thrombendartrectomy of common femoral artery in a single
      case. One-year patency rate in our series was 86.6%. It was 71.4% in thrombosis
      group. Limb salvage rate was 93.3%. CONCLUSION: Duplex arterial mapping could be
      used to differentiate the subacute ischemia with removable thrombus and chronic
      arterial occlusions guiding for the best revascularization procedure accordingly.

PMID- 25394959
TI  - Selected angiogenic factors in plasma of patients with lower limb symptomatic
      peripheral arterial disease: preliminary report.
AB  - AIM: The number of people suffering from atherosclerosis-related complications
      such as peripheral arterial disease (PAD) - including lower limbs PAD increases.
      Hypoxia and ischemia stimulate angiogenesis - a postnatal multistage process in
      which new blood vessels form and the Vascular Endothelial Growth Factor (VEGF-A)
      is the key proangiogenic factor whereas its soluble receptors type 1 and type 2
      (sVEGFR-1, sVEGFR-2) are regarded as inhibitory factors. The aim of this study
      was to assess the concentrations of VEGF-A, sVEGFR-1 and sVEGFR-2 in plasma of
      patients with symptomatic lower extremity PAD compared with selected clinical
      parameters (Ankle-Brachial Index, distance in walking test) and severity of PAD
      (according to the Fontaine classification). METHODS: The study group included 46
      patients suffering from symptomatic PAD with Fontaine class IIa-IV without any
      history of neoplastic disease. The control group consisted of 30 healthy non
      smoking volunteers. The following parameters were determined: plasma
      concentrations of VEGF-A, its soluble receptors (sVEGFR-1, sVEGFR-2) using the
      ELISA method also VEGF-A and sVEGFR-1 quotient was calculated on the basis of
      mean concentrations in homogenous units (pg/mL). RESULTS: The study group
      revealed a statistically significant higher level of VEGF-A concentration when
      compared with the control group and statistically significant lower concentration
      of sVEGFR-2 in the study group. In the study group a statistically significant
      negative correlation between VEGF-A concentrations and the length of irrelative
      distance in walking test was observed. In the group of PAD a significantly higher
      VEGF-A/sVEGFR-1 ratio in comparison with the control group was obtained. Within
      the group of patient suffering from PAD there was noticed an increasing VEGF
      A/sVEGFR-1 ratio in subsequent subgroups according to the Fontaine
      classification. CONCLUSION: The plasma concentrations of VEGF-A correlated with
      increased clinical symptoms of PAD in the walking test. The plasma VEGF-A/sVEGFR
      1 ratio may be used as a useful ischemic marker in patients with PAD which should
      be tested and finally verified in large group of patients.

PMID- 25394960
TI  - Proximal protection with hybrid stent, a safer combination for carotid artery
      stenting against carotid endarterectomy?
AB  - AIM: Carotid revascularization is an established theurapeutic modality in
      preventing stroke and death among patients with severe carotid stenosis. Although
      carotid endarterectomy remains as the primary option, carotid stenting is
      accepted as an alternative for patients with high risk for carotid
      endarterectomy. Recently published reports have better results with proximal
      protection devices when compared with distal protection devices. These studies
      have revealed less microembolic signals and less periprocedural new ischemic
      lesions on diffusion weighted magnetic resonance imaging. Stent choice may be
      also important for these procedures as open cell stent design has advantage of
      better flexibility whereas closed cell systems have an advantage of better
      scaffolding. Hybrid stents which are composed of open cells in the proximal and
      distal part and closed cells in the middle may carry both advantages. The aim of
      this study is to demonstrate whether combination of proximal protection devices
      with hybrid stents can be a safe alternative for carotid stenting in terms of
      periprocedural and 30-day outcomes. METHODS: Here we retrospectively evaluated 68
      symptomatic carotid stenosis patients undergoing carotid stenting with hybrid
      stent (Cristallo Ideale(r), Invatec s.r.l., Medtronic, Italy) and proximal
      protection device (MO.MA(r), Invatec s.r.l., Medtronic, Italy). RESULTS: Our
      results showed only 1 minor stroke in the periprocedural period and during the
      first 30-day after stenting, with no death or myocardial infarction. CONCLUSION:
      Although our case number is not large, we propose that carotid stenting may be
      safer with utilization of proximal protection system and hybrid type carotid
      stents.

PMID- 25394962
TI  - Reduction-responsive core-shell-corona micelles based on triblock copolymers:
      novel synthetic strategy, characterization, and application as a tumor
      microenvironment-responsive drug delivery system.
AB  - A facile and effective approach was established for fabricating core-shell-corona
      micelles by self-assembly of poly(ethylene glycol)-b-poly(acrylic acid-co-tert
      butyl acrylate)-poly(epsilon-caprolactone) (PEG43-b-P(AA30-co-tBA18)-b-PCL53)
      triblock copolymer, synthesized via a combination of ring-opening polymerization
      (ROP), atom transfer radical polymerization (ATRP), click chemistry, and
      hydrolyzation. The prenanovehicles with three different hydrolysis degrees from
      PEG43-b-PtBA48-b-PCL53 were developed to evaluate the drug loading capacity (DLC)
      and drug encapsulation efficiency (DEE). After cross-linking with a disulfide
      bond to regulate the drug release kinetics, the spherical core-shell-corona
      micelles with average diameter of 52 +/- 4 nm were obtained in aqueous solution.
      The reduction-responsive cross-linked micelles showed a slow sustained release in
      normal physiological conditions and a rapid release upon exposure to simulated
      tumor intracellular conditions. In addition, the cytotoxic analysis and HepG2
      cell growth inhibition assays demonstrated their remarkable biocompatibility and
      similar excellent anticancer activity as the free doxorubicin (DOX), which has
      also been revealed by the confocal laser scanning microscope (CLSM) analysis. So
      the reduction-sensitive core-shell-corona micelles are expected to be promising
      tumor microenvironment-responsive nanovehicles for hydrophobic drugs by
      glutathione (GSH) triggering. 

PMID- 25394961
TI  - Glycosylation of uroplakins. Implications for bladder physiopathology.
AB  - Urothelium, a specialized epithelium, covers the urinary tract and act not only
      as a barrier separating its light from the surrounding tissues, but fulfills an
      important role in maintaining the homeostasis of the urothelial tract and well
      being of the whole organism. Proper function of urothelium is dependent on the
      precise assemble of highly specialized glycoproteins called uroplakins, the end
      products and differentiation markers of the urothelial cells. Glycosylation
      changes in uroplakins correlate with and might reflect progressive stages of
      pathological conditions of the urothelium such as cancer, urinary tract
      infections, interstitial cystitis and others. In this review we focus on sugar
      components of uroplakins, their emerging role in urothelial biology and disease
      implications. The advances in our understanding of uroplakins changes in glycan
      moieties composition, structure, assembly and expression of their glycovariants
      could potentially lead to the development of targeted therapies and discoveries
      of novel urine and plasma markers for the benefit of patients with urinary tract
      diseases.

PMID- 25394964
TI  - [Revolt and monument: reflections on the scientific career of Rudolf Virchow].

PMID- 25394963
TI  - Incidence and risk factors of allograft bone failure after calcaneal lengthening.
AB  - BACKGROUND: Calcaneal lengthening with allograft is frequently used for the
      treatment of patients with symptomatic planovalgus deformity; however, the
      behavior of allograft bone after calcaneal lengthening and the risk factors for
      graft failure are not well documented. QUESTIONS/PURPOSES: (1) What proportion of
      the patients treated with allograft bone had radiographic evidence of graft
      failure and what further procedures were performed? (2) What are the risk factors
      for radiographic graft failure after calcaneal lengthening? (3) What patient
      factors are associated with the magnitude of correction achieved after calcaneal
      lengthening? METHODS: Between May 2003 and January 2014, we performed 341
      calcaneal lengthenings on 202 patients for planovalgus deformity, the etiology of
      which included idiopathic, cerebral palsy, and other neuromuscular disease. Of
      these, 176 patients (87%) had adequate followup for graft evaluation, defined as
      lateral radiographs taken before and at least 6 months after the index procedure
      (mean, 18 months; range, 6-100 months) and 117 patients (58%) had adequate
      followup for the assessment of the extent of correction, defined as weightbearing
      anteroposterior and lateral radiographs taken before and at least 1 year after
      the index procedure (mean, 24 months; range, 12-96 months). These patients'
      results were evaluated retrospectively. The Goldberg scoring system was chosen
      for demonstration of allograft behavior. A score lower than 6 at 6 months after
      surgery was defined as radiographic graft failure; the highest possible score was
      7 points, and this represented graft incorporation with excellent reorganization
      of the graft and no loss of height. The patient age, sex, diagnosis, graft
      material, ambulatory status, and use of antiseizure medication were evaluated as
      possible risk factors, and we controlled for the interaction of potentially
      confounding variables using multivariate analysis. Additionally, six radiographic
      indices were analyzed for their effects on the extent of correction. RESULTS: The
      mean estimated Goldberg score was 6 (SD, 1.14) at 6 months after calcaneal
      lengthening with 11 feet (4%) classified as radiographic graft failure (Goldberg
      score < 6). Of these, four feet (1%) underwent reoperation using an iliac
      autograft bone resulting from pain and loss of correction. Multivariate analysis
      showed that the tricortical iliac crest allograft was superior to the patellar
      allograft (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.1-9.8; p =
      0.038) and the possibility of radiographic graft failure was found to increase
      along with age (OR, 1.2; 95% CI, 1.0-1.3; p = 0.006). Radiographically, the
      extent of correction was found to decrease with patient age, as observed at the
      anteroposterior talus-first metatarsal angle (p < 0.001), lateral talocalcaneal
      angle (p < 0.001), lateral talus-first metatarsal angle (p < 0.001), and relative
      calcaneal length (p = 0.041). CONCLUSIONS: Graft failure can occur after
      calcaneal lengthening using allograft. Our study showed that the tricortical
      iliac allograft was superior to the patellar allograft, and further studies are
      warranted to further elucidate the effects of age on radiographic graft failure.
      LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 25394966
TI  - The 2015 WHO classification of lung tumors.

PMID- 25394965
TI  - [EEF1A2 inhibits the p53 function in hepatocellular carcinoma via PI3K/AKT/mTOR
      dependent stabilization of MDM4].
AB  - Upregulation of mouse double minute 4 (MDM4) is a frequent event in human
      hepatocellular carcinoma (HCC) but the underlying molecular mechanisms are poorly
      characterized. In this study a potential role of the phosphoinositide-3-kinase/v
      AKT murine thymoma viral oncogene homolog/mammalian target of rapamycin
      (PI3K/AKT/mTOR) cascade was investigated in the regulation of MDM4 in HCC.
      Inhibition of the PI3K-AKT and/or mTOR pathways lowered MDM4 protein levels in
      HCC cells. Mechanistic protection from proteasomal degradation resulted from de
      ubiquitination by ubiquitin-specific protease 2a and AKT-mediated phosphorylation
      of MDM4, thus increasing MDM4 protein levels. These findings were corroborated in
      a chimeric AKT mouse model. Upregulation of PI3K/AKT/mTOR signaling may result
      from overexpression of the eukaryotic elongation factor 1A2 (EEF1A2). Finally, a
      strong association between the expression of EEF1A2, phosphorylated AKT and MDM4
      was observed in human HCC samples. Strong activation of the
      EEF1A2/PI3K/AKT/mTOR/MDM4 signaling pathway was observed in HCC patients with
      short survival suggesting that targeting this axis might be a promising approach
      in a subset of HCC patients.

PMID- 25394967
TI  - [Value of core needle biopsy in preoperative diagnostics of soft tissue tumors:
      possibilities and limitations].
AB  - The differential diagnosis of soft tissue swellings encompasses a variety of
      benign, intermediate, low-grade malignant and high-grade neoplastic lesions in
      addition to tumor-like reactive processes. As treatment of these heterogeneous
      conditions varies greatly from conservative observation and simple local excision
      up to extensive radical surgical resection, treatment decisions are based mainly
      on a precise preoperative histological diagnosis on limited biopsy material. Even
      for clinically unequivocal sarcomas, the importance of the preoperative
      histological diagnosis has been increasingly emphasized as different therapeutic
      regimens have been established for different sarcoma types and the indications
      for preoperative treatment is influenced by the tumor grade and by the entity
      itself. Other factors positively influencing the increasing use of core needle
      biopsy for preoperative tumor diagnosis in soft tissue pathology are the
      availability of modern high-resolution imaging modalities as well as the
      establishment of several new second generation immunohistochemical markers and
      the discovery of entity-specific translocations detected by fluorescence in situ
      hybridization (FISH) in several sarcoma subtypes. In this review it will be shown
      that a targeted approach for processing core needle biopsies oriented towards the
      characteristic topographical, demographic, cytomorphological and architectural
      features of soft tissue lesions facilitates a precise diagnosis of soft tissue
      neoplasms in most cases. However, profound knowledge of the different aspects of
      soft tissue tumor diagnostics and familiarity with the frequent as well as the
      less common and rare tumor entities and variants is a prerequisite for
      appropriate interpretation of core needle biopsy findings and for selecting a
      limited but well-suited marker panel. The utilization of modern
      immunohistochemistry and/or FISH methods is highly useful for establishing the
      diagnosis of rare and unusual neoplasms in core needle biopsies. 

PMID- 25394968
TI  - [Continual self-renewal of the gastric epithelium by cell differentiation:
      implications for carcinogenesis].
AB  - BACKGROUND: The gastric mucosa and its glands represent a close interactive
      barrier to the outside world. This delicate surface is protected by a
      multilayered mucus barrier which contains among others the mucins MUC5AC and MUC6
      and the trefoil factor family peptide TFF2. Furthermore, two types of gastric
      glands form delicate homeostatic systems, i.e. the fundic and antral glands,
      which show continual bidirectional self-renewal via differentiation from stem and
      progenitor cells. It was the aim of this study to analyze the self-renewal of
      these gastric units. MATERIAL AND METHODS: Three characteristic regions (i.e.
      foveolar, proliferative zone and lower gland regions) were isolated from fundic
      and antral units by the use of laser microdissection and expression profiles
      concerning known marker genes were generated by reverse transcription polymerase
      chain reaction (RT-PCR) analysis. RESULTS: The surface mucous cells (SMCs) of
      fundic and antral units characteristically differed in the expression of certain
      secretory genes. Furthermore, the maturation of mucous neck cells and their trans
      differentiation into chief cells as well as the maturation of antral SMCs and
      antral gland cells occurred in a stepwise manner. DISCUSSION: The correct
      maturation particularly of mucous neck cells and their trans-differentiation into
      chief cells is critical for homeostatic self-renewal of fundic units.
      Dysregulation of this multistep process can result in generation of the
      spasmolytic polypeptide-expressing metaplasia (SPEM) lineage which is
      characterized by its strong ectopic TFF2 expression. Chronic inflammation is
      known to support SPEM formation. The SPEM lineage is a precancerous lesion which
      can further differentiate into intestinal metaplasia.

PMID- 25394969
TI  - [Inflammation, malignancy and immunology in gastrointestinal spindle cell tumors:
      what is beyond GIST?].
AB  - Many mesenchymal tumors and tumefactions associated with the gastrointestinal
      tract feature prominent inflammatory cells but the mechanisms for the
      inflammation and the processes themselves remain poorly understood. Such classic
      lesions include Kaposi sarcoma, inflammatory fibroid polyp, sclerosing
      mesenteritis and inflammatory myofibroblastic tumor but, more recently, the
      recognition of IgG4-related fibrosclerosing disease has resulted in modification
      of the views on pathogenesis and treatment of such inflammatory lesions in many
      anatomical sites. In some lesions the inflammation may reflect viral influences
      (Kaposi sarcoma) or a bacterial infectious trigger (IgG4-related fibrosclerosing
      disease) whereas in others such an interaction is unclear and alterations in
      various genes have been detected, such as anaplastic lymphoma receptor tyrosine
      kinase gene rearrangements in inflammatory myofibroblastic tumor and platelet
      derived growth factor receptor alpha (PDGFRA) gene mutations in inflammatory
      fibroid polyp and some gastrointestinal stromal tumors (GIST). Even the
      inflammatory milieu of GISTs may have an impact on the outcome. This article
      discusses the practical diagnostic considerations as well as the theoretical
      background. 

PMID- 25394970
TI  - [Molecular pathological diagnostics of infections in orthopedic pathology].
AB  - The diagnosis of infections in patients with arthritis and/or in joint prostheses
      requires interdisciplinary cooperation and the application of up-to-date methods.
      The histological investigation of the synovial membrane allows the
      differentiation of acute, chronic and granulomatous synovialitis. Detection of
      conserved regions of the microbial genome by PCR, especially 16S rRNA for
      bacteria and 18S rRNA for fungi, is a broad approach for the classification of
      pathogens which cannot be cultured. Acute infectious arthritis and periprosthetic
      infections share the spectrum of pathogens with sepsis, therefore multiplex PCR
      based methods for the detection of sepsis can be employed. Molecular diagnostics
      can detect minimal infections in periprosthetic tissues even after antibiotic
      therapy. The anamnesis (enteral or urogenital infection), clinical picture
      (oligoarthritis) and further parameters (e.g. HLA B27 status) are important for
      the diagnosis of reactive arthritis. In many cases of reactive arthritis,
      molecular methods allow the detection of bacterial DNA or RNA in synovial fluid
      or tissue samples. The low sensitivity of histopathological methods may be
      compensated by application of PCR techniques, especially in the differential
      diagnosis of granulomatous synovitis including mycobacterial infections.
      Molecular methods can be used to support the differential diagnosis of septic and
      reactive arthritis. MicroRNA techniques combined with PCR for detection of
      pathogens support the differential diagnosis of rheumatoid arthritis with severe
      inflammatory activity compared to infectious arthritis. Proteomic methods could
      expand the methodological spectrum for the diagnosis of infections. 

PMID- 25394971
TI  - [New surgical treatment options for bone tumors].
AB  - Primary bone neoplasms can be classified into benign, locally/aggressive and
      rarely metastasizing and malignant tumors. Patients with benign tumors usually
      undergo surgical treatment in cases of local symptoms, mainly consisting of pain
      or functional deficits due to compression of important anatomical structures,
      such as nerves or blood vessels. Locally/aggressive and rarely metastasizing
      tumors exhibit an infiltrative growth pattern, so that surgical treatment is
      necessary to prevent further destruction of bone leading to local instability.
      Finally, the surgical treatment of malignant tumors is, with few exceptions,
      considered to be a prerequisite for long-term survival, either alone or in
      combination with systemic chemotherapy. Whereas the main objective of surgery in
      the treatment of benign tumors is relief of local symptoms with a minimum amount
      of damage to healthy tissue and minimizing the risk of local recurrence while
      ensuring bone stability in locally aggressive and rarely metastasizing tumors,
      the primary goal in the operative treatment of bone sarcomas is the resection of
      the tumor with clear surgical margins followed by defect reconstruction and the
      preservation of function. This review examines the current developments in the
      surgical treatment of primary bone neoplasms with respect to the management of
      the tumors and novel reconstructive options. 

PMID- 25394972
TI  - [Novel molecular aspects of chordomas].
AB  - Chordomas are rare and slowly growing malignant bone tumors which mostly occur in
      adults. These bone tumors are characterized by epithelial and mesenchymal
      aspects. It is suggested that they arise from remnants of the notochord because
      they are found along the axial skeleton (e.g. clival, spinal and sacrococcygeal
      locations). It appears that cytogenetic aberrations are not randomly found in
      this tumor group. Loss of chromosomal material (e.g. 1p, 3p, 10q, 13q and 14q) is
      more frequently found than gain of material (e.g. 7q, especially 7q33). Several
      studies demonstrated brachyury expression (T; 6q27) as a possible candidate gene
      in the oncogenesis of chordomas (e.g. knock down in the chordoma cell line U
      CH1). So far therapy consists of complete resection and irradiation, e.g. with
      carbon ions. Targeting therapy is not yet established in routine protocols but
      phase II studies with tyrosine kinase inhibitors have shown partial response of
      tumors and, in some studies stabilization of the disease has been described. 

PMID- 25394973
TI  - [Avoiding pitfalls in the diagnostics of bone neoplasms: importance of reference
      pathology].
AB  - Bone tumors account for only approximately 1% of the total number of malignant
      tumors in humans so that they are only rarely diagnosed and appropriate
      experience is difficult to acquire. Although the number of entities is limited
      there exist very different clinical and radiological images depending on the
      manifestation in the different regions of the skeleton. Bone tumors are also
      histologically structured very differently even within a particular entity. Prior
      to the histopathological diagnosis the location of the lesion within the entire
      skeleton and in relation to the tumor-bearing bone must be clarified based on
      imaging findings, i.e. which bone is affected, which portion of the bone is
      affected and is the tumor centrally located in the marrow cavity, in the area of
      the corticalis or on the outside? It is known that bone tumors show
      diagnostically relevant preferential locations in both the total skeleton as well
      as within the affected bone depending on the entity and that the age of onset
      also varies. In this article the most common reasons for errors in assessment are
      discussed. In most cases it is possible for reference pathology to still
      correctly classify specific cases by a consistent consideration of diagnostic
      radiology in combination with morphology. Although diagnostic progress for
      specific entities of bone tumors has been achieved using molecular methods, the
      established principle of interdisciplinary cooperation is the prerequisite for
      the correct diagnosis of these tumors. The therapeutic consequences for patients
      can be substantial and result in life-long functional limitations depending on
      the diagnosis (e.g. joint resection for osteosarcoma in childhood and
      adolescence). A correct diagnosis is therefore of great importance for far
      reaching therapeutic decision-making.

PMID- 25394974
TI  - [Inflammation as molecular target in chondrosarcoma].
AB  - Inflammation is a hallmark in the development and progression of malignant
      tumors. In chondrosarcoma the inflammatory changes are relatively discrete;
      however, tumor-associated macrophages (TAM) may exert tumor-promoting effects.
      Interleukin (IL)-1 is an inflammatory cytokine which is produced by TAMs and
      which leads to the expression of NF-kappaB-regulated genes in chondrosarcoma
      cells, such as vascular endothelial growth factor A (VEGF-A). Through IL-1
      antagonists and substances, such as curcumin IL-1-induced VEGF-A expression and
      angiogenesis can be blocked; therefore, IL-1-blockade provides an interesting
      therapy target for chondrosarcoma. 

PMID- 25394975
TI  - [Aberrant reparative tissue remodeling: histopathology and molecular pathology].
AB  - Not only tumorous infiltrations can lead to destruction of parenchymal organs but
      also the aberrant proliferation and matrix production of mesenchymal cells and
      vessels during a dysregulated repair attempt. This fibrogenesis is the result of
      a complex pathogenesis, which can be investigated in animal models but also in
      situ to harvest new biomarkers. This article deals particularly with the second
      method and summarizes molecular pathological findings in various model diseases
      for aberrant reparative tissue reconstruction. These model diseases include
      plexiform vasculopathy in pulmonary arterial hypertension (PAH), Quilty lesions
      in heart transplantation, bronchiolitis obliterans (BO), inflammatory airway
      remodeling and Epstein-Barr virus (EBV) induced smooth muscle proliferation
      (posttransplantation smooth muscle tumor, PTSMT).Using in situ molecular
      pathology, we were able to dismiss an assumed involvement of myofibroblastic
      cells in vessel reconstruction of the lung in PAH. We could also for the first
      time perform a comprehensive molecular characterization of the vascular
      remodeling and prove that plexiform vasculopathy represents a complex-regulated
      epiphenomenon of excessive pulmonary hypertension. This method also allowed us to
      describe for the first time the miRNA expression in PAH in a compartment-specific
      manner and to draw conclusions regarding the damaged overriding regulatory
      mechanisms. In the same way, we were also able to describe the chimeric character
      of the complex neoangiogenesis in the donor organ after heart
      transplantation.After lung transplantation, we identified for the first time a
      group of tissue-based molecular markers, which can predict later occurrence of BO
      even in morphologically normal transbronchial biopsies. In addition, we have
      documented for the first time the molecular characteristics of the
      morphologically analogous airway reconstruction in lung-transplanted and non
      transplanted patients. We could further elucidate the role of matrix
      metalloproteinases (MMP) and their antagonists in inflammatory airway
      reconstruction and deduce from this the resulting therapeutic implications.
      Accordingly, we were able to further clarify the origin, pathogenesis and the
      malignant potential of EBV-induced PTSMT and for the first time provide an
      evidence-based therapy recommendation and risk assessment.In summary, this
      article documents that in situ diagnostics can meet the requirements of the
      challenging parameters and issues of life sciences. It is to be expected that the
      technical possibilities will develop analogously to the increasing demands and
      the in situ method will move further into the focus of molecular pathology.

PMID- 25394976
TI  - [Prostaglandin E2: innovative approaches for tissue engineering of articular
      cartilage].
AB  - Chronic diseases, traumatic tissue defects and tumor resections lead to
      irreversible loss of tissue which are usually treated by reconstructive
      techniques or prostheses. Tissue engineering represents a change of paradigm from
      the structural replacement of damaged tissue to genuine regeneration of organ
      specific tissue with reconstruction of function. Therefore, autologous cells,
      biomaterials and growth factors are used to achieve this goal. Tissue engineering
      of articular cartilage is used in this article as an example of the successful
      identification of prostaglandin E2 (PGE2) as a growth factor during endochondral
      ossification. In addition PGE2 could be shown to be beneficial for a rapid
      phenotypical redifferentiation and synthesis of collagen II in human articular
      chondrocytes. Based on these findings the development of a combined construct of
      an oriented scaffold and release system is demonstrated. The innovative
      characterization of these cell-seeded constructs by the use of synchrotron
      microcomputed tomography (MUCT) permits non-destructive analysis even down to the
      cellular level. Our results indicate new requirements for the pathological
      anatomical diagnosis with a view to long-term effects of tissue engineering
      constructs, the biocompatibility of biodegradable biomaterials and even more
      important the regenerative potential of different lesions, with prediction of the
      outcome of tissue engineering-based strategies for individual patients. 

PMID- 25394977
TI  - [Mutational tumor profiles beyond organ and tissue specificity: implications for
      diagnostics and clinical study design].
AB  - The diagnostics and therapy of malignant tumors are based on the paradigm that
      cancer is an organ and tissue-specific disease. Comprehensive tumor mutation
      profiling data that has recently become available from next generation sequencing
      projects has made it possible to analyze whether the established anatomical tumor
      classification is reflected on the genetic level. Here, we review the results of
      a study on 4796 tumors of 14 major cancer types from the cancer genome atlas
      (TCGA) database, that on average 43% of tumors of a particular type are
      genetically more similar to tumors of a different anatomical origin and that the
      genetic tumor type corresponds to the anatomical type in only 57% of the cases.
      Furthermore, we discuss the implications of the complex mutation profiles and
      similarity patterns across cancers for diagnostics and clinical study design and
      explain why the comprehensive genomic data should be complemented by functional
      proteomic analyses.

PMID- 25394978
TI  - [Report of the working group on dermatopathology 2014].

PMID- 25394979
TI  - [Meeting of the working group on gynecological and breast pathology 2014].

PMID- 25394980
TI  - [Report of the working group on hematopathology 2014].

PMID- 25394981
TI  - [Report from the working group on cardiac, vascular, renal and transplantation
      pathology 2014].

PMID- 25394982
TI  - [Report of the working party on bone, joint and soft tissue pathology 2014].

PMID- 25394983
TI  - [Report of the working group on molecular pathology 2014].

PMID- 25394984
TI  - [Report of the working group on cytopathology 2014].

PMID- 25394985
TI  - [Waldemar Hort: 08.05.1925-05.06.2014].

PMID- 25394986
TI  - [Hans A. Kretzschmar: 03.01.1953-12.01.2014].

PMID- 25394987
TI  - Antibody screening tests variably overestimate the prevalence of hepatitis C
      virus infection among HIV-infected adults in Ghana.
AB  - HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the
      reliability of available seroprevalence estimates remains uncertain. The study
      aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care
      in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a
      population of 1520 HIV-infected adults, all HBsAg-positive subjects (n = 236) and
      a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA
      using pooled plasma; positive samples were genotyped by core and NS5B sequencing.
      HCV antibodies were detected by three commercial screening assays and confirmed
      by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95%
      confidence interval 0.0-1.9%), comprising 3/236 (1.3%; 0.0-2.8%) HBsAg-positive
      and 1/172 (0.6%; 0.0-1.8%) HBsAg-negative subjects. HCV RNA-positive subjects
      showed reactivity in all three antibody screening assays. Among HCV RNA-negative
      subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity
      by each screening assay, respectively, including two (3.0%) with reactivity by
      all three assays. Only one sample (1.5%) had confirmed antibody reactivity by
      line immunoassay indicating past HCV infection. HCV-positive subjects (three
      males, two females) were aged 30-46 years, by questionnaire-based interview
      reported surgical procedures and blood transfusion as risk factors for infection.
      HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned).
      Without further testing, HCV antibody screening assays variably overestimated HCV
      prevalence among HIV-infected subjects in Ghana. These findings inform the
      interpretation of previous seroprevalence estimates based upon screening assays
      alone.

PMID- 25394988
TI  - Carotid interventions and blood pressure.
AB  - Arterial baroreceptors are pressure sensors found in the carotid sinus near the
      bifurcation of the carotid artery and in the aortic arch. Carotid interventions,
      whether endovascular or surgical, affect this complicated control system and the
      post-interventional blood pressure behavior. Comparisons between the intervention
      techniques, however, are challenging due to the varying measurement methods,
      duration of observation, and patient populations. The question as to which
      interventional method is preferable, if undisturbed regulation of blood pressure
      is concerned, still remains unanswered. The fact that blood pressure events
      (i.e., hemodynamic instability, hypertension, unstable blood pressure) frequently
      occur both immediately after intervention and in the long term, mandates a
      particularly careful cardiopulmonary and blood pressure monitoring. Direct and
      indirect measurements of baroreceptor sensitivity can be helpful in identifying
      high-risk patients, although the association to hard clinical endpoints is rarely
      documented for methodological reasons. 

PMID- 25394989
TI  - Renal denervation in the treatment of resistant arterial hypertension.
AB  - Patients with resistant arterial hypertension have an increased risk of stroke,
      myocardial infarction, heart failure, and chronic kidney disease. In many cases,
      limitations of pharmacological treatment like intolerance and adherence to the
      antihypertensive medications are present in the clinical setting. In this
      context, new treatment options like trans-femoral sympathetic renal nerve
      denervation is, even after publication of the Symplicity HTN-3 trial, a promising
      new treatment option. 

PMID- 25394990
TI  - Anionic CH???X- hydrogen bonds: origin of their strength, geometry, and other
      properties.
AB  - CF3H as a proton donor was paired with a variety of anions, and its properties
      were assessed by MP2/aug-cc-pVDZ calculations. The binding energy of monoanions
      halide, NO3(-), formate, acetate, HSO4(-), and H2PO4(-) lie in the 12-17 kcal
      mol(-1) range, although F(-) is more strongly bound, by 26 kcal mol(-1). Dianions
      SO4(2-) and HPO4(2-) are bound by 27 kcal mol(-1), and trianion PO4(3-) by 45
      kcal mol(-1). When two O atoms are available on the anion, the CH???O(-) H-bond
      (HB) is usually bifurcated, although asymmetrically. The CH bond is elongated and
      its stretching frequency redshifted in these ionic HBs, but the shift is reduced
      in the bifurcated structures. Slightly more than half of the binding energy is
      attributed to Coulombic attraction, with smaller contributions from induction and
      dispersion. The amount of charge transfer from the anions to the sigma*(CH)
      orbital correlates with many of the other indicators of bond strength, such as
      binding energy, CH bond stretch, CH redshift, downfield NMR spectroscopic
      chemical shift of the bridging proton, and density at bond critical points.

PMID- 25394991
TI  - Managing hypoglycemia in diabetes may be more fear management than glucose
      management: a practical guide for diabetes care providers.
AB  - Diabetes management is complex and requires significant effort from the person
      with diabetes to achieve recommended self-management behaviours. Achieving
      guideline concordant self-management is made easier when the person with diabetes
      is committed to the behaviours. Ambivalence is the psychological state in which a
      person experiences inconsistent drives; both toward and away from the recommended
      behaviour. Ambivalence about achieving recommended control over blood glucose is
      expected in situations of hypoglycaemia, due to the associated dangers. In this
      paper we demonstrate that hypoglycaemia is a fear event and is likely to elicit
      strong drives to avoid future hypoglycaemia as a fear coping strategy. For many,
      this results in hyperglycaemia. If hyperglycaemia to avoid hypoglycaemia is a
      fear management strategy, then hypoglycaemia management should involve fear
      management. Few diabetes healthcare providers are trained, skilled and confident
      in fear management. The purpose of this paper is to review the evidence on the
      psychological consequences of hypoglycaemia and to outline fear management
      strategies that can be implemented by diabetes care providers. A step-by-step
      guide is provided to facilitate understanding of the process of the intervention.

PMID- 25394992
TI  - Determination of tetracycline antibiotics in fatty food samples by selective
      pressurized liquid extraction coupled with high-performance liquid chromatography
      and tandem mass spectrometry.
AB  - For the determination of trace residues of tetracycline antibiotics in fatty food
      samples, selective pressurized liquid extraction coupled with high-performance
      liquid chromatography and tandem mass spectrometry was applied in this study.
      Copper(II) isonicotinate was first used as online cleanup adsorbent in the
      selective pressurized liquid extraction process. The adsorbent to sample ratio,
      extraction temperature, extraction time, and recycle times, etc. were optimized.
      The tetracyclines in food samples of pork, chicken meat, and clam meat were
      detected by liquid chromatography with tandem mass spectrometry. Tetracycline was
      found at levels of 0.32 and 0.53 MUg/g and oxytetracycline was found at 0.14 and
      0.21 MUg/g in chicken meat and clam meat, respectively, while chlorotetracycline
      and deoxytetracycline were below the detection limit. The detection limit (S/N =
      3) for these four tetracyclines were from 0.2 to 3.3 ng/g, the recoveries were
      from 75.8 to 110.5%, and relative standard deviations were from 5.5 to 13.6%.
      Copper(II) isonicotinate showed a higher purification capacity than other cleanup
      adsorbents for extraction of antibiotics in fatty food and the recovery showed
      predominance compared with a pressurized liquid extraction method without
      adsorbent. The study demonstrated that copper(II) isonicotinate would be a
      promising cleanup adsorbent in pressurized liquid extraction for the analysis of
      trace organic pollutants in complicated samples. 

PMID- 25394993
TI  - Proteolytically stabilizing fibronectin without compromising cell and gelatin
      binding activity.
AB  - Excessive proteolytic degradation of fibronectin (FN) has been implicated in
      impaired tissue repair in chronic wounds. We previously reported two strategies
      for stabilizing FN against proteolytic degradation; the first conjugated
      polyethylene glycol (PEG) through cysteine residues and the second conjugated PEG
      chains of varying molecular weight on lysine residues. PEGylation of FN via
      lysine residues resulted in increased resistance to proteolysis with increasing
      PEG size, but an overall decrease in biological activity, as characterized by
      cell and gelatin binding. Our latest method to stabilize FN against proteolysis
      masks functional regions in the protein during lysine PEGylation. FN is PEGylated
      while it is bound to gelatin Sepharose beads with 2, 5, and 10 kDa PEG
      precursors. This results in partially PEGylated FN that is more stable than
      native FN and whose proteolytic stability increases with PEG molecular weight.
      Unlike completely PEGylated FN, partially PEGylated FN has cell adhesion, gelatin
      binding, and matrix assembly responses that are comparable to native FN. This is
      new evidence of how PEGylation variables can be used to stabilize FN while
      retaining its activity. The conjugates developed herein can be used to dissect
      molecular mechanisms mediated by FN stability and functionality, and address the
      problem of FN degradation in chronic wounds.

PMID- 25394996
TI  - Embodied markedness of parity? Examining handedness effects on parity judgments.
AB  - Parity is important semantic information encoded by numbers. Interestingly, there
      are hand-based effects in parity judgment tasks: right-hand responses are faster
      for even and left-hand responses for odd numbers. As this effect was initially
      explained by the markedness of the words even vs. odd and right vs. left, it was
      denoted as the linguistic markedness of response codes (MARC) effect. In the
      present study, we investigated whether the MARC effect differs for right and left
      handers. We conducted a parity judgment task, in which right- and left-handed
      participants had to decide whether a presented single or two-digit number was odd
      or even by pressing a corresponding response key. We found that handedness
      modulated the MARC effect for unit digits. While we replicated a regular MARC
      effect for right handers, there was no evidence for a MARC effect for left
      handers. However, closer inspection revealed that the MARC effect in left handers
      depended on the degree of left-handedness with a reversed MARC effect for most
      left-handed participants. Furthermore, although parity of tens digits interfered
      with the processing of unit digits, the MARC effect for tens digits was not
      modulated by handedness. Our findings are discussed in the light of three
      different accounts for the MARC effect: the linguistic markedness account, the
      polarity correspondence principle, and the body-specificity hypothesis. 

PMID- 25394997
TI  - Attention-deficit/hyperactivity disorder symptoms in children with traumatic
      dental injuries.
AB  - AIM: The aim of this study was to compare the symptoms of attention
      deficit/hyperactivity disorder (ADHD) in children with TDIs with to non-injured
      children. MATERIAL AND METHODS: Children between 7 and 16 years old who were
      admitted to the Selcuk University, Faculty of Dentistry, for treatment of dental
      trauma were included in the study group (SG). As a control group (CG), children
      with no reported history of dental trauma were recruited. The Conners' Parent
      Rating Scale-Revised: Short Form (CPRS-R: S) was used to assess ADHD symptoms.
      RESULTS: Both groups, SG and CG, composed of 55 children. There were no
      significant differences in age, gender, and duration of education between SG and
      CG. Children with TDIs had significantly higher CPRS-R: S Hyperactivity scores.
      Hyperactivity level was positively correlated with the history of previous dental
      trauma. There were no associations between number of injured teeth, type of
      injury, and ADHD symptoms. CONCLUSIONS: These findings suggest that children with
      TDIs have more hyperactive symptoms than children without dental trauma.
      Clinicians should screen ADHD symptoms in children with TDIs and refer them for
      treatment when necessary.

PMID- 25394998
TI  - Mervyn Susser's legacy in perinatal epidemiology.

PMID- 25394999
TI  - Mervyn Susser and the logic of scientific discovery.

PMID- 25395000
TI  - Failure rates of class V restorations in the management of root caries in adults 
      a systematic review.
AB  - OBJECTIVE: The aim of this systematic review was to compare cumulative failure
      rates of different restorative materials in carious class V lesions on the root
      surfaces of adult patients. BACKGROUND: The prevalence of root caries is set to
      increase in the coming years as a result of ageing of the population and a
      concomitant reduction in levels of edentulousness. Evidence is needed to assist
      practitioners to select the most appropriate restorative material for use in
      these lesions. METHODS: A search of the literature was undertaken using the
      electronic databases of PubMed, Embase, CENTRAL and OpenSIGLE using keywords
      relevant to the search question. Two review authors conducted the electronic
      search independently, and any conflict was resolved by discussion. The references
      quoted in the full text articles extracted were hand searched for any further
      eligible studies. RESULTS: Sixty non-duplicate citations were screened. Following
      review of the titles, abstracts, texts and application of the pre-determined
      inclusion/exclusion criteria, five studies remained. CONCLUSION: There is a need
      for more research in this area as many of the studies identified in this
      systematic review treated post-radiation, xerostomic patients which are not
      typical of the general population. Increased adherence to CONSORT guidelines for
      reporting is also advised to facilitate future systematic review and meta
      analysis in this area.

PMID- 25395001
TI  - Dr. Earl N. Meyer, in the lab, with a scalpel: a murder mystery as a biochemistry
      recruitment tool.
AB  - Increasing student participation in science is an ongoing challenge for many
      universities. In this active learning workshop, centered on inquiry and teamwork,
      we introduce high-school students to biochemistry and molecular biology
      techniques using a murder mystery activity. During this intensive 3 hr workshop,
      we engage students in a murder scenario entitled "The Case of the Silenced
      Scientist." A commercially available DNA fingerprinting kit was used as a basis
      to create a customized scenario whereby students collaborate with one another to
      solve a murder mystery. Through analysis of DNA samples taken from the crime
      scene and suspects, students can identify the murderer while developing
      technical, teamwork, and critical thinking skills. Emphasis is placed on teamwork
      by immersing students in the collaborative process of research inquiry. Though
      short in duration, this workshop aims to build student relationships to science
      through creativity and exploration. In this article, we describe the key
      customized applications of this workshop as a blueprint for science recruitment.
      We focus on the workshop facilitators' perceived learning impact on students.

PMID- 25395006
TI  - Assessment of the sensitizing potency of preservatives with chance of skin
      contact by the loose-fit coculture-based sensitization assay (LCSA).
AB  - Parabens, methylisothiazolinone (MI) and its derivative
      methylchloroisothiazolinone (MCI), are commonly used as preservatives in personal
      care products. They can cause hypersensitivity reactions of the human skin. We
      have tested a set of nine parabens, MI alone and in combination with MCI in the
      loose-fit coculture-based sensitization assay (LCSA). The coculture of primary
      human keratinocytes and allogenic dendritic cell-related cells (DC-rc) in this
      assay emulates the in vivo situation of the human skin. Sensitization potency of
      the test substances was assessed by flow cytometric analysis of the DC-rc
      maturation marker CD86. Determination of the concentration required to cause a
      half-maximal increase in CD86-expression (EC50sens) allowed a quantitative
      evaluation. The cytotoxicity of test substances as indicator for irritative
      potency was measured by 7-AAD (7-amino-actinomycin D) staining. Parabens
      exhibited weak (methyl-, ethyl-, propyl- and isopropylparaben) or strong (butyl-,
      isobutyl-, pentyl- and benzylparaben) effects, whereas phenylparaben was found to
      be a moderate sensitizer. Sensitization potencies of parabens correlated with
      side chain length. Due to a pronounced cytotoxicity, we could not estimate an
      EC50sens value for MI, whereas MI/MCI was classified as sensitizer and also
      showed cytotoxic effects. Parabens showed no (methyl- and ethylparaben) or weak
      irritative potencies (propyl-, isopropyl-, butyl-, isobutyl-, phenyl- and
      benzylparaben), only pentylparaben was rated to be irritative. Overall, we were
      able to demonstrate and compare the sensitizing potencies of parabens in this in
      vitro test. Furthermore, we showed an irritative potency for most of the
      preservatives. The data further support the usefulness of the LCSA for comparison
      of the sensitizing potencies of xenobiotics.

PMID- 25395007
TI  - SEURAT-1 liver gold reference compounds: a mechanism-based review.
AB  - There is an urgent need for the development of alternative methods to replace
      animal testing for the prediction of repeat dose chemical toxicity. To address
      this need, the European Commission and Cosmetics Europe have jointly funded a
      research program for 'Safety Evaluation Ultimately Replacing Animal Testing.' The
      goal of this program was the development of in vitro cellular systems and
      associated computational capabilities for the prediction of hepatic, cardiac,
      renal, neuronal, muscle, and skin toxicities. An essential component of this
      effort is the choice of appropriate reference compounds that can be used in the
      development and validation of assays. In this review, we focus on the selection
      of reference compounds for liver pathologies in the broad categories of
      cytotoxicity and lipid disorders. Mitochondrial impairment, oxidative stress, and
      apoptosis are considered under the category of cytotoxicity, while steatosis,
      cholestasis, and phospholipidosis are considered under the category of lipid
      dysregulation. We focused on four compound classes capable of initiating such
      events, i.e., chemically reactive compounds, compounds with specific cellular
      targets, compounds that modulate lipid regulatory networks, and compounds that
      disrupt the plasma membrane. We describe the molecular mechanisms of these
      compounds and the cellular response networks which they elicit. This information
      will be helpful to both improve our understanding of mode of action and help in
      the selection of appropriate mechanistic biomarkers, allowing us to progress the
      development of animal-free models with improved predictivity to the human
      situation. 

PMID- 25395008
TI  - Current research on cell death mechanisms.

PMID- 25395009
TI  - Activation of the chemosensing transient receptor potential channel A1 (TRPA1) by
      alkylating agents.
AB  - The transient receptor potential ankyrin 1 (TRPA1) cation channel is expressed in
      different tissues including skin, lung and neuronal tissue. Recent reports
      identified TRPA1 as a sensor for noxious substances, implicating a functional
      role in the molecular toxicology. TRPA1 is activated by various potentially
      harmful electrophilic substances. The chemical warfare agent sulfur mustard (SM)
      is a highly reactive alkylating agent that binds to numerous biological targets.
      Although SM is known for almost 200 years, detailed knowledge about the
      pathophysiology resulting from exposure is lacking. A specific therapy is not
      available. In this study, we investigated whether the alkylating agent 2
      chloroethyl-ethylsulfide (CEES, a model substance for SM-promoted effects) and SM
      are able to activate TRPA1 channels. CEES induced a marked increase in the
      intracellular calcium concentration ([Ca(2+)]i) in TRPA1-expressing but not in
      TRPA1-negative cells. The TRP-channel blocker AP18 diminished the CEES-induced
      calcium influx. HEK293 cells permanently expressing TRPA1 were more sensitive
      toward cytotoxic effects of CEES compared with wild-type cells. At low CEES
      concentrations, CEES-induced cytotoxicity was prevented by AP18. Proof-of-concept
      experiments using SM resulted in a pronounced increase in [Ca(2+)]i in HEK293-A1
      E cells. Human A549 lung epithelial cells, which express TRPA1 endogenously,
      reacted with a transient calcium influx in response to CEES exposure. The CEES
      dependent calcium response was diminished by AP18. In summary, our results
      demonstrate that alkylating agents are able to activate TRPA1. Inhibition of
      TRPA1 counteracted cellular toxicity and could thus represent a feasible approach
      to mitigate SM-induced cell damage. 

PMID- 25395011
TI  - The Gordon Scott Topical Collection: articles on peste des petits ruminants and
      other infectious diseases of domestic livestock.

PMID- 25395010
TI  - A genomic and evolutionary approach reveals  non-genetic drug resistance in
      malaria.
AB  - BACKGROUND: Drug resistance remains a major public health challenge for malaria
      treatment and eradication. Individual loci associated with drug resistance to
      many antimalarials have been identified, but their epistasis with other
      resistance mechanisms has not yet been elucidated. RESULTS: We previously
      described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene
      that confer resistance to halofuginone. We describe here the evolutionary
      trajectory of halofuginone resistance of two independent drug resistance
      selections in Plasmodium falciparum. Using this novel methodology, we discover an
      unexpected non-genetic drug resistance mechanism that P. falciparum utilizes
      before genetic modification of the cPRS. P. falciparum first upregulates its
      proline amino acid homeostasis in response to halofuginone pressure. We show that
      this non-genetic adaptation to halofuginone is not likely mediated by
      differential RNA expression and precedes mutation or amplification of the cPRS
      gene. By tracking the evolution of the two drug resistance selections with whole
      genome sequencing, we further demonstrate that the cPRS locus accounts for the
      majority of genetic adaptation to halofuginone in P. falciparum. We further
      validate that copy-number variations at the cPRS locus also contribute to
      halofuginone resistance. CONCLUSIONS: We provide a three-step model for multi
      locus evolution of halofuginone drug resistance in P. falciparum. Informed by
      genomic approaches, our results provide the first comprehensive view of the
      evolutionary trajectory malaria parasites take to achieve drug resistance. Our
      understanding of the multiple genetic and non-genetic mechanisms of drug
      resistance informs how we will design and pair future anti-malarials for clinical
      use.

PMID- 25395012
TI  - The use of chromium(III) to supercharge peptides by protonation at low basicity
      sites.
AB  - The addition of chromium(III) nitrate to solutions of peptides with seven or more
      residues greatly increases the formation of doubly protonated peptides, [M +
      2H](2+), by electrospray ionization. The test compound heptaalanine has only one
      highly basic site (the N-terminal amino group) and undergoes almost exclusive
      single protonation using standard solvents. When Cr(III) is added to the
      solution, abundant [M + 2H](2+) forms, which involves protonation of the peptide
      backbone or the C-terminus. Salts of Al(III), Mn(II), Fe(III), Fe(II), Cu(II), Zn
      (II), Rh(III), La(III), Ce(IV), and Eu(III) were also studied. Although several
      metal ions slightly enhance protonation, Cr(III) has by far the greatest ability
      to generate [M + 2H](2+). Cr(III) does not supercharge peptide methyl esters,
      which suggests that the mechanism involves interaction of Cr(III) with a
      carboxylic acid group. Other factors may include the high acidity of hexa
      aquochromium(III) and the resistance of Cr(III) to reduction. Nitrate salts
      enhance protonation more than chloride salts and a molar ratio of 10:1
      Cr(III):peptide produces the most intense [M + 2H](2+). Cr(III) also supercharges
      numerous other small peptides, including highly acidic species. For basic
      peptides, Cr(III) increases the charge state (2+ versus 1+) and causes the number
      of peptide molecules being protonated to double or triple. Chromium(III) does not
      supercharge the proteins cytochrome c and myoglobin. The ability of Cr(III) to
      enhance [M + 2H](2+) intensity may prove useful in tandem mass spectrometry
      because of the resulting overall increase in signal-to-noise ratio, the fact that
      [M + 2H](2+) generally dissociate more readily than [M + H](+), and the ability
      to produce [M + 2H](2+) precursors for electron-based dissociation techniques. 

PMID- 25395013
TI  - An Intervention to Promote Breast Milk Production in Mothers of Preterm Infants.
AB  - A pilot study was conducted to estimate the effects of a breast milk expression
      education and support intervention on breast milk production outcomes in mothers
      of very and extremely preterm infants. Forty mothers of hospitalized preterm
      infants (<30 weeks of gestation) were randomized to the experimental intervention
      or standard care for 6 weeks. Duration and frequency of breast milk expressions
      and volume of expressed breast milk were measured daily. Samples of breast milk
      were collected thrice during the study and analyzed for their lipid
      concentration. Mothers in the experimental group had a statistically significant
      higher duration of breast milk expression in min/day (p= .043). Differences
      observed between the two groups regarding the frequency of breast milk
      expression, volume of breast milk, and lipid concentration were not statistically
      significant. Results suggest that the experimental intervention may promote
      breast milk production in mothers of very and extremely preterm infants. 

PMID- 25395015
TI  - Formation and maintenance of neuronal assemblies through synaptic plasticity.
AB  - The architecture of cortex is flexible, permitting neuronal networks to store
      recent sensory experiences as specific synaptic connectivity patterns. However,
      it is unclear how these patterns are maintained in the face of the high spike
      time variability associated with cortex. Here we demonstrate, using a large-scale
      cortical network model, that realistic synaptic plasticity rules coupled with
      homeostatic mechanisms lead to the formation of neuronal assemblies that reflect
      previously experienced stimuli. Further, reverberation of past evoked states in
      spontaneous spiking activity stabilizes, rather than erases, this learned
      architecture. Spontaneous and evoked spiking activity contains a signature of
      learned assembly structures, leading to testable predictions about the effect of
      recent sensory experience on spike train statistics. Our work outlines
      requirements for synaptic plasticity rules capable of modifying spontaneous
      dynamics and shows that this modification is beneficial for stability of learned
      network architectures. 

PMID- 25395014
TI  - Evaluation of an integrated clinical workflow for targeted next-generation
      sequencing of low-quality tumor DNA using a 51-gene enrichment panel.
AB  - BACKGROUND: Improvements in both performance and cost for next-generation
      sequencing (NGS) have spurred its rapid adoption for clinical applications. We
      designed and optimized a pan-cancer target-enrichment panel for 51 well
      established oncogenes and tumor suppressors, in conjunction with a bioinformatic
      pipeline informed by in-process controls and pre- and post-analytical quality
      control measures. METHODS: The evaluation of this workflow consisted of
      sequencing mixtures of intact DNA to establish analytical sensitivity and
      precision, utilization of heuristics to identify systematic artifacts, titration
      studies of intact and FFPE samples for input optimization, and incorporation of
      orthogonal sequencing strategies to increase both positive predictive value and
      variant detection. We also used 128 FFPE samples to assess clinical accuracy and
      incorporated the previously described quantitative functional index (QFI) for
      sample qualification as part of detailing complete system performance. RESULTS:
      We observed a concordance correlation coefficient of 0.99 between the observed
      versus expected percent variant at 250 ng input across 4 independent sequencing
      runs. A subset of the systematic variants were confirmed to be barely detectable
      on an independent sequencing platform (Wilcox signed-rank test p-value <10(-16)),
      and the incorporation of orthogonal sequencing strategies increased the harmonic
      mean of sensitivity and positive predictive value of mutation detection by 41%.
      In one cohort of FFPE tumor samples, coverage and inter-platform concordance were
      positively correlated with the QFI, emphasizing the need for pre-analytical
      sample quality control to reduce the risk of false positives and negatives. In a
      separate cohort of FFPE samples, the 51-gene panel achieved 78% sensitivity (95%
      CI = 56.3, 92.5) with 100% PPV (95% CI = 81.5, 100.0) based on known mutations at
      7.9% median abundance. By sequencing specimens using an orthogonal NGS
      technology, sensitivity was improved to 87.0% (95% CI = 66.4,97.2) while
      maintaining PPV. CONCLUSIONS: The results highlight the value of process
      integration in a comprehensive targeted NGS system, enabling both discovery and
      diagnostic applications, particularly when sequencing low-quality cancer
      specimens.

PMID- 25395017
TI  - Investigation of effects of Giardia duodenalis on transcellular and paracellular
      transport in enterocytes using in vitro Ussing chamber experiments.
AB  - The mechanisms by which different genotypes of Giardia duodenalis result in
      different symptoms remain unresolved. In particular, we lack detailed knowledge
      on which transport mechanisms (transcellular or paracellular) are affected by
      different Giardia isolates. Using horse radish peroxidase (HRP) and creatinine as
      transcellular and paracellular probes, respectively, we developed a robust assay
      that can be used with an Ussing chamber to investigate epithelial transport, as
      well as short-circuit current as an indicator of net ion transport. We
      investigated 2 Giardia isolates, both Assemblage A, one a lab-adapted strain and
      the other a field isolate. Results indicate that products from sonicated Giardia
      trophozoites increase both transcellular and paracellular transport. A non
      significant increase in transepithelial electrical resistance (TEER) and short
      circuit current were also noted. The paracellular transport was increased
      significantly more in the field isolate than in the lab-adapted strain. Our
      results indicate that while both transcellular and paracellular transport
      mechanisms may be increased following exposure of cells to Giardia trophozoite
      sonicate, perhaps by inducing non-specific increases in cellular traffic, it is
      important that in vitro studies of Giardia pathophysiology are conducted with
      different Giardia isolates, not just lab-attenuated strains. 

PMID- 25395016
TI  - Adiponectin reduces carotid atherosclerotic plaque formation in ApoE-/- mice:
      roles of oxidative and nitrosative stress and inducible nitric oxide synthase.
AB  - Adiponectin (APN) is an important anti-atherogenic adipocytokine. The aim of the
      present study was to investigate the role of adiponectin in atherosclerotic
      plaque formation and clarify its mechanisms. An atherosclerosis model was induced
      by in vivo perivascular constrictive silica collar placement on the left common
      carotid arteries in male apolipoprotein E-deficient (ApoE-/-) mice. All of the
      mice were fed a high-fat diet, and divided into phosphate-buffered saline,
      adenovirus (Ad)-beta-galactosidase and Ad-APN treatment groups. Compared with
      treatment of Ad-beta-gal or PBS, Ad-APN treatment markedly reduced inducible
      nitric oxide synthase (iNOS) protein expression, decreased in nitric
      oxide/superoxide production, blocked peroxynitrite formation and reversed the
      progression of atherosclerotic lesions. Adiponectin may be a natural molecule
      that reduces atherosclerosis by inhibiting iNOS and consequently diminishing
      oxidative/nitrative stress.

PMID- 25395018
TI  - Cystic fibrosis and physiological responses to exercise.
AB  - Cardiopulmonary exercise testing is underutilized within the clinical management
      of patients with cystic fibrosis. But within the last 5 years, there has been
      considerable interest in its implementation, which has included deliberations by
      the European Cystic Fibrosis Society about incorporating this method within the
      clinical assessment of patients. This review examines the current use of
      cardiopulmonary exercise testing in assessing the extent and cause(s) of exercise
      limitation from a pediatric perspective. Examples of the measured parameters and
      their interpretation are provided. Critical synthesis of recent work in the
      oxygen uptake (VO2) kinetics response to and following exercise is also
      discussed, and although identified more as a research tool, its utilization
      advances researchers understanding of the cardiovascular, respiratory and
      muscular limitations to exercise tolerance. Finally, exercise and its application
      in therapeutic interventions are highlighted and a number of recommendations made
      about the utility of exercise prescription. 

PMID- 25395019
TI  - The role of endobronchial ultrasound/esophageal ultrasound for evaluation of the
      mediastinum in lung cancer.
AB  - The introduction: of ultrasound-based, minimally invasive techniques
      (Endobronchial Ultrasound guided Transbronchial Needle Aspiration (EBUS-TBNA) and
      Esophageal Ultrasound guided Fine Needle Aspiration) has revolutionized care of
      patients with lung cancer needing mediastinal lymph node sampling. When combined,
      the techniques offer safe and accurate assessment of mediastinum, with accuracy
      surpassing that of the pervious gold standard - cervical mediastinoscopy. EBUS
      TBNA can be used for mediastinal restaging in both, patients with suspected
      recurrence following treatment for primary lung cancer and followingneoadjuvant
      therapy in preparation for definitive surgical intervention. Both EBUS-TBNA and
      esophageal ultrasound guided fine needle aspiration techniques have been shown to
      provide sufficient material for molecular and DNA testing, extending their role
      beyond initial evaluation of the mediastinum to help direct and personalize
      medical treatment and predict response to therapy. In the future, assessing
      sonographic features of lymph nodesmay become useful in predicting nodal
      metastasis, further increasing the sensitivity of these techniques for detection
      of metastatic disease. 

PMID- 25395020
TI  - Serum paraoxonase 1 (PON1) activity in acute pancreatitis of dogs.
AB  - OBJECTIVES: Serum paraoxonase 1 is considered a marker of inflammation and
      oxidative damage. The aims of this study were to evaluate changes in serum
      paraoxonase 1 activity in dogs with acute pancreatitis, to correlate serum
      paraoxonase 1 activity and other analytes known to be altered in dogs with
      pancreatitis and to assess the relationship between serum paraoxonase 1 activity
      and disease severity in dogs with acute pancreatitis. MATERIALS AND METHODS:
      Retrospective analysis of dogs with acute pancreatitis and healthy dogs in which
      serum paraoxonase 1 activity was measured were compared. RESULTS: Median serum
      paraoxonase 1 activity was significantly lower in dogs with pancreatitis (n = 19)
      compared to healthy ones (n = 19). Serum paraoxonase 1 activity was negatively
      correlated with serum lipase and amylase activities, and C-reactive protein and
      haptoglobin concentrations and was positively correlated with total cholesterol
      and glucose concentration. Disease severity was negatively correlated with serum
      paraoxonase 1 activity and positively correlated with triglyceride and C-reactive
      protein concentration. CLINICAL SIGNIFICANCE: Serum paraoxonase 1 activity is
      lower in dogs with acute pancreatitis and together with triglyceride and C
      reactive protein concentrations is a potential marker of disease severity.

PMID- 25395021
TI  - Power calculations for delta-adjusted pattern-mixture models.
AB  - Pattern-mixture models provide a general and flexible framework for sensitivity
      analyses of nonignorable missing data in longitudinal studies. The delta-adjusted
      pattern-mixture models handle missing data in a clinically interpretable manner
      and have been used as sensitivity analyses addressing the effectiveness
      hypothesis, while a likelihood-based approach that assumes data are missing at
      random is often used as the primary analysis addressing the efficacy hypothesis.
      We describe a method for power calculations for delta-adjusted pattern-mixture
      model sensitivity analyses in confirmatory clinical trials. To apply the method,
      we only need to specify the pattern probabilities at postbaseline time points,
      the expected treatment differences at postbaseline time points, the conditional
      covariance matrix of postbaseline measurements given the baseline measurement,
      and the delta-adjustment method for the pattern-mixture model. We use an example
      to illustrate and compare various delta-adjusted pattern-mixture models and use
      simulations to confirm the analytic results.

PMID- 25395022
TI  - Clinical and diagnostic features of perioperative hypersensitivity to cefuroxime.
AB  - INTRODUCTION: The Danish Anaesthesia Allergy Centre (DAAC) investigated 89 adult
      patients with suspected perioperative cefuroxime-associated hypersensitivity
      reactions between 2004 and 2013. The goals were to determine whether the time to
      index reaction after cefuroxime exposure could be used to implicate cefuroxime as
      the cause of the reactions and explore different test modalities in diagnosing
      cefuroxime hypersensitivity. METHOD: Skin tests, in vitro tests, and titrated
      provocations were used to determine cefuroxime hypersensitivity. Patients were
      deemed cefuroxime positive on the basis of at least two positive tests and/or a
      positive provocation. RESULTS: One or more tests were positive for cefuroxime in
      24 of 89 (27.0%) patients. One was only specific IgE positive and was deemed
      cefuroxime negative. Twenty-three (25.8%) were deemed cefuroxime positive. There
      were four specific IgE-, 4 histamine release test-, 13 skin test-, and 14
      provocation positive patients. There were eight (34.8%) patients who were only
      provocation positive. Data on time to index reaction after cefuroxime exposure
      were available for 80 patients (22 in the positive group and 58 in the negative
      group), 22 of 22 (100%) of positive patients reacted in <15 min vs. only 38 of 58
      (65.5%) of negative patients. CONCLUSION: All patients with confirmed
      hypersensitivity to cefuroxime reacted within 15 min of administration, but so
      did 65.5% of Cefuroxime negative patients, making timing of administration an
      unreliable predictor of causation in the perioperative setting. Provocations were
      always positive when carried out in skin test positive patients; however, eight
      patients had positive provocations only, highlighting the need for provocation in
      skin test negative patients.

PMID- 25395023
TI  - One author replies.

PMID- 25395024
TI  - Re.: "Reduced risk of lung cancer with metformin therapy in diabetic patients: a
      systematic review and meta-analysis".

PMID- 25395025
TI  - Urinary concentrations of benzophenone-type ultraviolet radiation filters and
      couples' fecundity.
AB  - Concern has arisen about benzophenone (BP) ultraviolet (UV) radiation filters,
      given their use in sunscreen and personal-care products and their reported
      estrogenic and antiandrogenic activity. We recruited 501 couples who were
      discontinuing use of contraceptives in order to become pregnant for the
      Longitudinal Investigation of Fertility and the Environment (LIFE) Study
      (Michigan and Texas, 2005-2009). Couples provided urine specimens and completed
      daily journals until they either achieved pregnancy or had tried for 12 months.
      Women used fertility monitors to time sexual intercourse and digital pregnancy
      tests. Urinary concentrations of 5 UV filters (ng/mL) were determined using
      triple-quadrupole mass spectrometry: 2,4-dihydroxybenzophenone (also called BP
      1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone
      (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8); and 4-hydroxybenzophenone.
      Fecundability odds ratios were estimated for each UV filter (dichotomized at the
      75th percentile) and adjusted for age, creatinine concentration, body mass index
      (weight (kg)/height (m)(2)), cotinine concentration, season, and site, while
      accounting for time off contraception. Separate models were fitted for each UV
      filter and partner; final models included partners' concentrations. Male
      partners' concentrations of BP-2 and 4-hydroxybenzophenone were associated with
      reduced fecundity in adjusted models (fecundability odds ratio (FOR) = 0.69 (95%
      confidence interval (CI): 0.50, 0.95) and FOR = 0.74 (95% CI: 0.54, 1.00),
      respectively). In models adjusting for both partners' concentrations, male BP-2
      concentration remained associated with reduced fecundity (FOR = 0.69, 95% CI:
      0.49, 0.97). These data suggest that male exposure to select UV filters may
      diminish couples' fecundity, resulting in a longer time to pregnancy. 

PMID- 25395026
TI  - Interactions between cigarette smoking and fine particulate matter in the Risk of
      Lung Cancer Mortality in Cancer Prevention Study II.
AB  - The International Agency for Research on Cancer recently classified outdoor air
      pollution and airborne particulate matter as carcinogenic to humans. However,
      there are gaps in the epidemiologic literature, including assessment of possible
      joint effects of cigarette smoking and fine particulate matter (particulate
      matter less than or equal to 2.5 um in diameter) on lung cancer risk. We present
      estimates of interaction on the additive scale between these risk factors from
      Cancer Prevention Study II, a large prospective US cohort study of nearly 1.2
      million participants recruited in 1982. Estimates of the relative excess risk of
      lung cancer mortality due to interaction, the attributable proportion due to
      interaction, and the synergy index were 2.19 (95% confidence interval (CI): 
      0.10, 4.83), 0.14 (95% CI: 0.00, 0.25), and 1.17 (95% CI: 1.00, 1.37),
      respectively, using the 25th and 75th percentiles as cutpoints for fine
      particulate matter. This suggests small increases in lung cancer risk among
      persons with both exposures beyond what would be expected from the sum of the
      effects of the individual exposures alone. Although reductions in cigarette
      smoking will achieve the greatest impact on lung cancer rates, these results
      suggest that attempted reductions in lung cancer risk through both tobacco
      control and air quality management may exceed expectations based on reducing
      exposure to either risk factor alone. 

PMID- 25395027
TI  - Invited commentary: How big is that interaction (in my community)--and in which
      direction?
AB  - In an accompanying article, Turner et al. (Am J Epidemiol. 2014;180(12):1145
      1149) compare the joint effects of smoking and air pollution to make inferences
      about the reduction in lung cancer mortality achieved when reducing each exposure
      separately and when reducing both together. In this commentary, we use first
      principles to quantify the difference between the risk or mortality reduction
      obtained from reducing each of 2 exposures together and the sum of the risk
      differences obtained from reducing the 2 exposures separately. Metrics of the
      impact of joint effects or comparisons of joint effects presented in units of
      absolute risk, such as Rothman's I, can provide more meaningful quantitative
      measures of public health impact than unitless metrics (e.g., ratios) and
      standardized metrics (e.g., the population attributable fraction) of potential
      interventions for reducing smoking and air pollution exposure. In particular, the
      venerable attributable community risk metric can provide an estimate of the
      community impact of such interventions in units of absolute risk. A spreadsheet
      we provide demonstrates the calculation of the various metrics for hypothetical
      data similar to those reported by Turner et al. Using algebra, graphics, and
      examples, we show that positive interaction, or synergy, on the additive scale
      implies that the impact on risk reduction from a program that applies both
      interventions will be lesser than the sum of the impacts of the separate
      interventions. 

PMID- 25395028
TI  - Endometrial cells sense and react to tissue damage during infection of the bovine
      endometrium via interleukin 1.
AB  - Cells generate inflammatory responses to bacteria when pattern recognition
      receptors bind pathogen-associated molecules such as lipopolysaccharide. Cells
      may also respond to tissue damage by sensing damage-associated molecules.
      Postpartum bacterial infections of the bovine uterus cause endometritis but the
      risk of disease is increased by tissue trauma triggered by dystocia. Animals that
      suffered dystocia had increased concentrations of inflammatory mediators IL-8, IL
      1beta and IL-1alpha in vaginal mucus 3 weeks postpartum, but they also had more
      bacteria than normal animals. Ex vivo organ cultures of endometrium, endometrial
      cells and peripheral blood monocytes did not generate inflammatory responses to
      prototypical damage molecules, HMGB1 or hyaluronan, or to necrotic cells;
      although they secreted IL-6 and IL-8 in a concentration-dependent manner when
      treated with IL-1alpha. However, necrotic endometrial cells did not accumulate
      intracellular IL-1alpha or release IL-1alpha, except when pre-treated with
      lipopolysaccharide or bacteria. Endometrial cell inflammatory responses to IL
      1alpha were dependent on the cognate receptor IL-1R1, and the receptor adaptor
      protein MyD88, and the inflammatory response to IL-1alpha was independent of the
      response to lipopolysaccharide. Rather than a typical damage-associated molecule,
      IL-1alpha acts to scale the inflammatory response in recognition that there is a
      combination of pathogen challenge followed by endometrial cell damage. 

PMID- 25395029
TI  - Activation of PPARgamma by 12/15-lipoxygenase during cerebral ischemia
      reperfusion injury.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) expression and
      activity are increased in brain ischemic injury and its agonists have shown
      potential for brain injury protection. The influence of 12/15-lipoxygenase (12/15
      LOX) on the activity of PPARgamma in oxygen-glucose deprivation (OGD) and
      ischemia-reperfusion (I/R) was investigated. A middle cerebral artery
      occlusion/reperfusion model with Sprague Dawley (SD) rats was established. For
      I/R intervention, the rats were treated with the 12/15-LOX-derived product 12
      hydroxyeicosatetraenoic acid (12-HETE) for 30 min before cerebral artery
      occlusion. Primary cortical neurons from SD rats were used to establish an OGD
      cell model. 12-HETE or a 12/15-LOX antisense oligonucleotide (asON-12/15-LOX) was
      added to OGD-treated neurons. Western blots, immunofluorescence and enzyme-linked
      immunosorbent assays detected protein. Reverse transcription-polymerase chain
      reaction analyzed the expression of the PPARgamma target genes. PPARgamma-DNA
      binding activity was determined by peroxisome proliferator responsive element
      luciferase reporter vectors. 12/15-LOX total protein increased significantly with
      I/R, and expression of 12-HETE was also upregulated. 12-HETE treatment increased
      PPARgamma protein expression and inhibited inducible nitric oxide synthase
      protein expression, which was upregulated with I/R. PPARgamma nuclear protein and
      12/15-LOX total protein expression in OGD-treated neurons increased
      significantly. 12-HETE treatment increased the expression of PPARgamma nuclear
      protein, upregulated the mRNA levels of PPARgamma target genes (lipoprotein
      lipase and acyl-CoA oxidase) and enhanced PPARgamma-DNA binding activity. asON
      12/15-LOX treatment inhibited 12/15-LOX and PPARgamma protein expression and
      lipoprotein lipase mRNA. Cerebral I/R injury in rats and OGD treatment in neurons
      promoted 12/15-LOX expression, and 12-HETE activated PPARgamma. Therefore,
      PPARgamma can be activated by the 12/15-LOX pathway during cerebral I/R injury.

PMID- 25395030
TI  - High tuberculosis burden among people living with HIV in southern Mozambique.

PMID- 25395031
TI  - Cladribine improves lung cysts and pulmonary function in a child with
      histiocytosis.

PMID- 25395032
TI  - Dead space: the physiology of wasted ventilation.
AB  - An elevated physiological dead space, calculated from measurements of arterial
      CO2 and mixed expired CO2, has proven to be a useful clinical marker of prognosis
      both for patients with acute respiratory distress syndrome and for patients with
      severe heart failure. Although a frequently cited explanation for an elevated
      dead space measurement has been the development of alveolar regions receiving no
      perfusion, evidence for this mechanism is lacking in both of these disease
      settings. For the range of physiological abnormalities associated with an
      increased physiological dead space measurement, increased alveolar
      ventilation/perfusion ratio (V'A/Q') heterogeneity has been the most important
      pathophysiological mechanism. Depending on the disease condition, additional
      mechanisms that can contribute to an elevated physiological dead space
      measurement include shunt, a substantial increase in overall V'A/Q' ratio,
      diffusion impairment, and ventilation delivered to unperfused alveolar spaces. 

PMID- 25395033
TI  - Spirometric reference values for Malagasy adults aged 18-73 years.
AB  - The American Thoracic Society (ATS) and European Respiratory Society (ERS)
      recommend that spirometry prediction equations be derived from samples of similar
      race/ethnicity. Malagasy prediction equations do not exist. The objectives of
      this study were to establish prediction equations for healthy Malagasy adults,
      and then compare Malagasy measurements with published prediction equations. We
      enrolled 2491 healthy Malagasy subjects aged 18-73 years (1428 males) from June
      2006 to April 2008. The subjects attempted to meet the ATS/ERS 2005 guidelines
      when performing forced expiratory spirograms. We compared Malagasy measurements
      of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and
      FEV1/FVC with predictions from the European Community for Steel and Coal (ECSC),
      the third National Health and Nutrition Examination Survey (NHANES III) and the
      ERS Global Lung Function Initiative (GLI) 2012 study. A linear model for the
      entire population, using age and height as independent variables, best predicted
      all spirometry parameters for sea level and highland subjects. FEV1, FVC and
      FEV1/FVC were most accurately predicted by NHANES III African-American male and
      female, and by GLI 2012 black male and black and South East Asian female
      equations. ECSC-predicted FEV1, FVC and FEV1/FVC were poorly matched to Malagasy
      measurements. We provide the first spirometry reference equations for a healthy
      adult Malagasy population, and the first comparison of Malagasy population
      measurements with ECSC, NHANES III and GLI 2012 prediction equations.

PMID- 25395034
TI  - A contemporary survival analysis of individuals with cystic fibrosis: a cohort
      study.
AB  - Previously established predictors of survival may no longer apply in the current
      era of cystic fibrosis (CF) care. Our objective was to identify risk factors
      associated with survival in a contemporary CF population. We used the Canadian CF
      Registry, a population-based cohort, to calculate median age of survival and
      summarise patient characteristics from 1990 to 2012. Clinical, demographic and
      geographical factors, and survival were estimated for a contemporary cohort (2000
      2012) using Cox proportional hazards models. There were 5787 individuals in the
      registry between 1990 and 2012. Median survival age increased from 31.9 years
      (95% CI 28.3-35.2 years) in 1990 to 49.7 years (95% CI 46.1-52.2 years) in the
      most current 5-year window ending in 2012. Median forced expiratory volume in 1 s
      improved (p=0.04) and fewer subjects were malnourished (p<0.001) over time.
      Malnourished patients (hazard ratio (HR) 2.1, 95% CI 1.6-2.8), those with
      multiple exacerbations (HR 4.5, 95% CI 3.2-6.4) and women with CF-related
      diabetes (HR 1.8, 95% CI 1.2-2.7) were at increased risk of death. Life
      expectancy in Canadians with CF is increasing. Modifiable risk factors such as
      malnutrition and pulmonary exacerbations are associated with an increased risk of
      death. The sex gap in CF survival may be explained by an increased hazard for
      death in women with CF-related diabetes. 

PMID- 25395035
TI  - Availability, price and affordability of anti-tuberculosis drugs in Europe: a
      TBNET survey.
AB  - Data on availability and cost of anti-tuberculosis (TB) drugs in relation to
      affordability at national level are scarce. We performed a cross-sectional study
      on availability and cost of anti-TB drugs at major TB-reference centres in 37
      European countries. Costs of standardised treatment regimens used for pan
      sensitive TB, multidrug-resistant (MDR) TB, pre-extensively drug-resistant (XDR)
      TB, and XDR-TB were compared using a purchasing power analysis. Affordability was
      evaluated in relation to monthly national gross domestic products per capita
      (GDP). At least one second-line injectable and either moxifloxacin or
      levofloxacin were available in all countries. Linezolid and clofazimine were
      available in 79% and 46% of the countries, respectively. Drug cost for XDR-TB was
      three-times more expensive than those for MDR-TB. The average price of treatment
      for pan-sensitive TB represented a maximum of 8.5% of the monthly GDP across
      countries, while for standard MDR-TB treatment this was <30% in only six
      countries and more than 100% in four countries. Treatment of XDR-TB represented
      more than 100% of a month's GDP in all countries where the regimen was available.
      High cost and limited availability of drugs for treatment of drug-resistant TB,
      particularly beyond resistance to first-line drugs, are a major impediment to
      successful TB control in Europe. 

PMID- 25395036
TI  - Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a
      long-term extension study (CHEST-2).
AB  - Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of
      inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension
      (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk
      profile and improved several clinically relevant end-points in patients with
      CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and
      efficacy of riociguat. Eligible patients from CHEST-1 received riociguat
      individually adjusted up to a maximum dose of 2.5 mg three times daily. The
      primary objective was the safety and tolerability of riociguat; exploratory
      efficacy end-points included 6-min walking distance (6MWD) and World Health
      Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2
      and 211 (89%) were ongoing at this interim analysis (March 2013). The safety
      profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety
      signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to
      1 year in CHEST-2. In the observed population at 1 year, mean+/-sd 6MWD had
      changed by +51+/-62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had
      improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1
      baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and
      apparently showed sustained benefits in exercise and functional capacity for up
      to 1 year. 

PMID- 25395037
TI  - Serum 25-hydroxyvitamin D levels and lung function in adults with asthma: the
      HUNT Study.
AB  - The association between vitamin D status and lung function in adults with asthma
      remains unclear. We studied this cross-sectional association and possible
      modification by sex and allergic rhinitis in 760 adults (aged 19-55 years) with
      self-reported asthma in the Nord-Trondelag Health Study. Serum 25-hydroxyvitamin
      D (25(OH)D) level <50 nmol.L(-1) was considered deficient. Lung function
      measurements included forced expiratory volume in 1 s (FEV1) % predicted, forced
      vital capacity (FVC) % predicted and FEV1/FVC ratio. Multiple linear regression
      models were used to estimate adjusted regression coefficients (beta) and 95%
      confidence intervals. 44% of asthma adults had serum 25(OH)D levels <50 nmol.L(
      1). Its associations with lung function measures seemed to be modified by sex and
      allergic rhinitis (p<0.03 for three-way interaction term). Overall, a serum
      25(OH)D level <50 nmol.L(-1) was not associated with lung function measurements
      in subjects with allergic rhinitis in this asthma cohort. In men with asthma but
      without allergic rhinitis, however, a serum 25(OH)D level <50 nmol.L(-1) was
      significantly associated with lower FEV1/FVC ratio (beta=-8.60%; 95% CI: -16.95%-
      -0.25%). Low serum 25(OH)D level was not associated with airway obstruction in
      most asthma adults with the exception of men with asthma but without allergic
      rhinitis. 

PMID- 25395038
TI  - Early-life risk factors for chronic nonrespiratory diseases.
AB  - We have witnessed a change in disease patterns contributing to the global burden
      of disease, with a shift from early childhood deaths due to the classic
      infectious communicable diseases to years lived with disability from chronic
      noncommunicable diseases. In both developing and developed countries, the years
      lived with disability attributable to chronic disease have increased:
      cardiovascular diseases by 17.7%; chronic respiratory disease by 8.5%;
      neurological conditions by 12.2%; diabetes by 30.0%; and mental and behavioural
      disorders by 5.0% over the past 20 years. Recognition of the contribution made by
      adverse environmental exposures in early life to noncommunicable diseases in
      later life is increasing. These early-life exposures appear to contribute to both
      chronic respiratory and chronic nonrespiratory diseases. In this State of the Art
      article, we aim to examine early-life environmental exposures that have an
      epidemiological association with chronic nonrespiratory diseases, such as obesity
      and type II diabetes, cardiovascular disease, and neurocognitive and behavioural
      problems. We will highlight the potential overlap in environmental risks with
      respiratory diseases, and point out knowledge gaps and research opportunities. 

PMID- 25395039
TI  - Can we read the future from a tree?

PMID- 25395040
TI  - Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney: a detailed
      study of radiological, pathological and clinical outcomes.
AB  - OBJECTIVE: To characterise the clinical, radiological and histological features
      of mucinous tubular and spindle cell carcinoma (MTSCC), as well as oncological
      outcomes. PATIENTS AND METHODS: This is a single institution retrospective
      analysis of all patients with MTSCC from 2002 to 2011. Patients were excluded if
      MTSCC could not be confirmed on pathology re-review (four patients). Clinical
      characteristics, pathology, imaging, and outcomes were reviewed for the 19
      included patients. RESULTS: The median (range) age at diagnosis was 59 (17-71)
      years with a female predominance (78.9%). On contrast-enhanced computed
      tomography, MTSCC enhanced less than the cortex during the corticomedullary
      phase. The mean (range) tumour attenuation was 36 (24-48), 67 (41-133), 89 (49
      152), and 76 (52-106) Hounsfield units in the pre-contrast, corticomedullary,
      nephrographic and excretory phases, respectively. In all, 16 patients were
      treated with partial (five patients) or radical nephrectomy (11) for pT1 (62.5%),
      pT2 (31.3%), and pT3a disease (6.3%). One patient underwent active surveillance.
      Of three patients (13.0%) managed with energy ablation, there was one recurrence
      that was treated with salvage surgery. One patient (5.3%) had metastatic disease
      at diagnosis and died from disease 64.7 months later. A patient with a pT2bN0M0
      MTSCC with sarcomatoid dedifferentiation developed bone metastases 9.5 months
      after diagnosis and was alive at 19.0 months. The remainder were free of
      recurrence or progression. CONCLUSION: MTSCC is a rare renal cell carcinoma (RCC)
      variant. In this largest series to date, MTSCC presented at a broad range of ages
      and displayed a female predilection. Imaging and pathological features of MTSCC
      display some overlap with papillary RCC. MTSCC is associated with excellent
      outcomes overall, but is not universally indolent.

PMID- 25395041
TI  - Cerebral venous thrombosis in inflammatory bowel disease.
AB  - Cerebral venous thrombosis (CVT) is a rare but devastating complication of
      inflammatory bowel disease (IBD). Here we describe six IBD patients with cerebral
      venous thrombosis. The patients presented with hours to days of headache and were
      found to have venous thrombosis on imaging. Four of the six patients had
      ulcerative colitis and two had Crohn's disease. All six patients were treated
      with therapeutic anticoagulation. There were two deaths; one patient became
      comatose and died despite anticoagulation while the other recovered well from the
      sinus thrombosis but died after a bowel perforation 3 weeks later. This case
      series demonstrates the critical need for early recognition of neurological
      symptoms in patients with IBD during disease flares. It is important to recognize
      the clinical signs in order to start anticoagulation expeditiously and improve
      neurological outcomes. 

PMID- 25395042
TI  - Two-stage model for time-varying effects of discrete longitudinal covariates with
      applications in analysis of daily process data.
AB  - This study proposes a generalized time-varying effect model that can be used to
      characterize a discrete longitudinal covariate process and its time-varying
      effect on a later outcome that may be discrete. The proposed method can be
      applied to examine two important research questions for daily process data:
      measurement reactivity and predictive validity. We demonstrate these applications
      using health risk behavior data collected from alcoholic couples through an
      interactive voice response system. The statistical analysis results show that the
      effect of measurement reactivity may only be evident in the first week of
      interactive voice response assessment. Moreover, the level of urge to drink
      before measurement reactivity takes effect may be more predictive of a later
      depression outcome. Our simulation study shows that the performance of the
      proposed method improves with larger sample sizes, more time points, and smaller
      proportions of zeros in the binary longitudinal covariate.

PMID- 25395043
TI  - An overview of hedgehog signaling in fibrosis.
AB  - The Hedgehog (Hh) signaling pathway plays a key role during embryogenesis and
      tissue regeneration. Recently, studies revealed that overactivated Hh signaling
      leads to fibrogenesis in many types of tissues. The activation of Hh signaling is
      involved in the epithelial-mesenchymal transition and excessive extracellular
      matrix deposition. Blockade of Hh signaling abolishes the induction of the
      epithelial-mesenchymal transition and ameliorates tissue fibrosis. Therefore, new
      therapeutic targets to alleviate fibrosis based on the Hh signaling have
      attracted a great deal of attention. This is a new strategy for treating fibrosis
      and other related diseases. In this review, we discuss the crucial role of Hh
      signaling in fibrogenesis to provide a better understanding of their relationship
      and to encourage the study of novel targeted therapies. 

PMID- 25395044
TI  - Docking and free energy perturbation studies of ligand binding in the kappa
      opioid receptor.
AB  - The kappa opioid receptor (KOR) is an important target for pain and depression
      therapeutics that lack harmful and addictive qualities of existing medications.
      We present a model for the binding of morphinan ligands and JDTic to the
      JDTic/KOR crystal structure based on an atomic level description of the water
      structure within its active site. The model contains two key interaction motifs
      that are supported by experimental evidence. The first is the formation of a salt
      bridge between the ligand and Asp 138(3.32) in transmembrane domain (TM) 3. The
      second is the stabilization by the ligand of two high energy, isolated, and ice
      like waters near TM5 and TM6. This model is incorporated via energetic terms into
      a new empirical scoring function, WScore, designed to assess interactions between
      ligands and localized water in a binding site. Pairing WScore with the docking
      program Glide discriminates known active KOR ligands from large sets of decoy
      molecules much better than Glide's older generation scoring functions, SP and XP.
      We also use rigorous free energy perturbation calculations to provide evidence
      for the proposed mechanism of interaction between ligands and KOR. The molecular
      description of ligand binding in KOR should provide a good starting point for
      future drug discovery efforts for this receptor. 

PMID- 25395046
TI  - Erratum to: Enhanced insulin sensitivity and acute regulation of metabolic genes
      and signaling pathways after a single electrical or manual acupuncture session in
      female insulin-resistant rats.

PMID- 25395045
TI  - Genome-free hepatitis B virion levels in patient sera as a potential marker to
      monitor response to antiviral therapy.
AB  - Complete virions of hepatitis B virus (HBV) contain a DNA genome that is enclosed
      in a capsid composed of the HBV core antigen (HBcAg), which is in turn surrounded
      by a lipid envelope studded with viral surface antigens (HBsAg). In addition, HBV
      infected cells release subviral particles composed of HBsAg only (HBsAg 'spheres'
      and 'filaments') or HBsAg enveloping HBcAg but devoid of viral DNA ('empty
      virions'). The hepatitis B e antigen (HBeAg), a soluble antigen related to HBcAg,
      is also secreted in some HBV-infected patients. The goals of this study were to
      explore the levels of empty virions in HBV-infected patients before and during
      therapy with the nucleotide analog tenofovir disoproxil fumarate (TDF) that
      inhibits HBV DNA synthesis and the relationships of empty virions to complete
      virions, HBsAg and HBeAg. HBV DNA, HBcAg and HBsAg levels were determined in
      serum samples from 21 patients chronically infected with HBV and enrolled in
      clinical TDF studies. Serum levels of empty virions were found to exceed levels
      of DNA-containing virions, often by >= 100-fold. Levels of both empty and
      complete virions varied and were related to the HBeAg status. When HBV DNA
      replication was suppressed by TDF, empty virion levels remained unchanged in most
      but were decreased (to the limit of detection) in some patients who also
      experienced significant decrease or loss of serum HBsAg. In conclusion, empty
      virions are present in the serum of chronic hepatitis B patients at high levels
      and may be useful in monitoring response to antiviral therapy.

PMID- 25395047
TI  - Fibrocalculous pancreatic diabetes (FCPD).
AB  - Fibrocalculous pancreatic diabetes (FCPD) is an uncommon form of diabetes that
      occurs as a result of chronic calcific pancreatitis, in the absence of alcohol
      abuse. The disease is restricted to tropical regions of the world, and southern
      India has the highest known prevalence of FCPD. The typical patient with FCPD is
      a lean adolescent or young adult of either sex, presenting with history of
      recurrent bouts of abdominal pain and steatorrhea. Demonstration of large,
      discrete pancreatic calculi by plain radiographs or ultrasonography of the
      abdomen is diagnostic. While the exact etiology of FCPD is unknown, genetic,
      nutritional and inflammatory factors have been hypothesized to play a role.
      Diabetes in FCPD is often brittle and difficult to control; most patients require
      multiple doses of insulin for control of glycemia. However, in spite of high
      blood glucose levels, patients rarely develop ketosis. Malabsorption responds to
      pancreatic enzyme supplementation. Surgical removal of stones is indicated for
      symptomatic relief of intractable pain. While patients with FCPD develop
      microvascular complications as frequently as those with type 2 diabetes,
      macrovascular disease is uncommon. Development of pancreatic malignancy is the
      most dreaded complication and should be suspected in any patient who complains of
      weight loss, back pain or jaundice. 

PMID- 25395048
TI  - Performance evaluation of the Xpert MTB/RIF assay according to its clinical
      application.
AB  - BACKGROUND: The Xpert MTB/RIF assay (Xpert assay; Cepheid, Sunnyvale, CA) is
      becoming the test of choice for the rapid diagnosis of tuberculosis and rifampin
      (RIF) resistance. The aim of this study was to evaluate the performance of the
      Xpert assay with respect to its clinical application at a tertiary care hospital
      in Korea, a country with an intermediate tuberculosis burden and high-resource.
      METHODS: A total of 303 Xpert assay results from 109 smear-positive and 194 smear
      negative respiratory specimens were retrospectively reviewed. Based on patients'
      medical records, four categories of clinical applications of the Xpert assay were
      identified: (1) the diagnosis of pulmonary tuberculosis in patients with a high
      probability of pulmonary tuberculosis according to their clinical and
      radiological features; (2) the exclusion of tuberculosis in clinically
      indeterminate patients for pulmonary tuberculosis; (3) the differentiation of
      Mycobacterium tuberculsosis (MTB) from nontuberculous mycobacteria in a smear
      positive specimen; and (4) the diagnosis of RIF resistance. Standard culture and
      drug susceptibility tests were used as reference methods. RESULTS: The
      sensitivity of the Xpert assay for MTB detection in category 1 was 89.8% (95%
      confidence interval [CI], 78.5-95.8%), but 66.7% (95% CI, 12.5-98.2%) in category
      2. The positive predictive values ranged from 33.3% (95% CI, 6.0-75.9%) in
      category 2 to 91.3% and 91.7% in categories 1 and 3, respectively. The negative
      predictive values were over 90% in all categories. The Xpert assay correctly
      detected RIF resistance in six of the seven (85.7%) isolates tested. CONCLUSIONS:
      The Xpert assay exhibited variable performance according to its clinical
      application; this finding cautions that careful interpretation for the results of
      this assay would be needed according to its intended purpose.

PMID- 25395049
TI  - The modified Gibson approach to the acetabulum.
AB  - OBJECTIVE: Providing a surgical approach similar to the Kocher-Langenbeck but
      having improved anterosuperior access, less risk of injury to branches of the
      inferior gluteal nerve supplying the anterior portion of the gluteus maximus
      muscle, and improved cosmesis. INDICATIONS: Any surgery that would otherwise call
      for the Kocher-Langenbeck approach. CONTRAINDICATIONS: Fractures of the anterior
      column and/or wall; transtectal T-shaped fractures. Transverse fractures and
      infra/juxtatectal T-shaped fractures having the major displacement anteriorly at
      the pelvic brim with only minor posterior displacement. SURGICAL TECHNIQUE:
      Exposure of the acetabulum fracture through a straight skin incision, developing
      the plane between the anterior border of the gluteus maximus muscle and the
      tensor fasciae latae. The gluteus maximus is reflected posteriorly to reveal the
      underlying deep anatomic structures. POSTOPERATIVE MANAGEMENT: Thromboprophylaxis
      and prophylaxis as indicated for the prevention of heterotopic ossification are
      instituted. The patient is mobilized as quickly as the associated injuries will
      allow. Toe-touch weight-bearing is continued for 10-12 weeks. However,
      progression to full weight-bearing should be individualized. RESULTS: Between
      1996 and 2000, 16 patients having a fracture of the acetabulum were operated on
      through the modified Gibson approach with 15 patients followed up for 1 year or
      more. Fracture types were posterior wall in eight patients, transverse in one,
      posterior column and wall in two, transverse and posterior wall in four, and T
      shaped in one. There were no intraoperative or immediate postoperative
      complications. Clinical outcome was determined using a modification of the method
      developed by Merle d'Aubigne and Postel and was good-to-excellent in 14 patients
      and poor in one (a patient who developed osteonecrosis of the femoral head
      unrelated to the approach).

PMID- 25395050
TI  - [Arthroscopic release for shoulder stiffness].
AB  - OBJECTIVE: Arthroscopic capsular release for refractory shoulder stiffness to
      recreate active and passive shoulder joint mobility. INDICATIONS: Adhesive
      capsulitis of the shoulder (primary and secondary frozen shoulder) after
      receiving at least 3 months of conservative treatment. CONTRAINDICATIONS: Boney
      related stiffening of the shoulder joint, joint infection, freezing phase of the
      primary frozen shoulder and shoulder stiffness after reconstructive surgery.
      SURGICAL TECHNIQUE: Opening of the lower shoulder joint capsule over a gentle
      unidirectional manipulation under general anesthesia. A diagnostic arthroscopy in
      lateral position with extension of the arm is then performed. The release is
      completed with incision of the ventral and the dorsal part of the capsule under
      arthroscopic control. POSTOPERATIVE MANAGEMENT: While still in the operation
      room, the anesthetist places an interscalene brachial plexus catheter, thus,
      delivering the best possible analgesia. This enables full range of active and
      passive movement of the shoulder joint for at least 3 days. Outpatient
      continuation of physiotherapy with anti-inflammatory and analgesic medication.
      RESULTS: The literature shows good functional results with age- and gender
      related Constant scores greater than 75 %. Our retrospective inquiry of 37 cases
      with a mean follow-up of 40 months confirms this outcome. The disease duration
      was shortened by arthroscopic release. Ability to work was achieved after a mean
      of 1.9 months; treatment ended 3.6 months after operation. In 10 cases with
      secondary shoulder stiffness, residual symptoms remained.

PMID- 25395051
TI  - Extended medial approach in posteromedial proximal tibia fracture dislocation.
AB  - OBJECTIVE: Treatment of posteromedial proximal tibia fracture dislocation (medial
      Moore type II, Schatzker IV) with a one-incision technique. INDICATIONS:
      Posteromedial proximal tibia fracture dislocation Moore type II (medial).
      CONTRAINDICATIONS: All Moore type V fracture patterns requiring a bilateral
      approach. SURGICAL TECHNIQUE: In supine position, an extended strictly medial
      incision is performed. It is mandatory to preserve the medial collateral ligament
      and the pes anserinus. In a first step, the posterolateral impressed zone is
      reduced directly through the main fracture gap using an image intensifier. The
      posteromedial main fragment is then reduced and preliminarily fixed with
      Kirschner wires. A posteromedial buttress plate slid in under the medial
      ligamentous structures supports this fragment. Anterior subcutaneous dissection
      revolves the medial boarder of the patellar ligament and a medial arthrotomy is
      performed. The bony avulsed anterior cruciate ligament (ACL) is reduced and
      suture fixation follows. POSTOPERATIVE MANAGEMENT: Immediate partial weight
      bearing is possible. RESULTS: A collective of 26 patients could be evaluated
      after a median follow-up of 4 years (1-8 years). Median age was 51 years (20-77
      years). All fractures healed without secondary displacement or infection. After a
      median of 4 years, 25 patients showed no to moderate osteoarthritis. One patient
      showed severe osteoarthritis after 8 years. All patients subjectively judged the
      clinical result as good to excellent. The average Lysholm score was 95 (75-100)
      and the average Tegner activity score 5 (3-7).

PMID- 25395052
TI  - Double locking plate fixation of sacral fractures in unstable pelvic ring C-type
      injuries.
AB  - OBJECTIVE: Alternative sacrum fixation with double-plate osteosynthesis in
      vertical unstable pelvic fractures. The surgical technique allows anatomic
      reduction and osteosynthesis of the sacrum component. INDICATIONS: All vertical
      unstable pelvic ring fractures 61-C type according to AO/OTA system with
      associated displaced sacrum fractures CONTRAINDICATIONS: Hemodynamic unstable
      patients, fractures with major sacroiliac joint involvement, nondisplaced sacrum
      fractures. SURGICAL TECHNIQUE: In prone position, a midline incision exposing the
      sacrum fracture is needed. The fracture is distracted and interjacent bone
      fragments or hematoma can be evacuated. The fracture is anatomically reduced and
      compressed. Two anatomically bent 3.5-mm locked compression plates (LCP) are
      placed on the dorsal aspect of the sacrum. In Denis type II and III fractures,
      the lateral screws can be placed in the lateral aspect of the sacrum. In Denis
      type I fractures, the lateral screws are placed in the ilium lateral to the
      sacroiliac joint to improve purchase. Additional short monocortical locking
      screws in the middle part of the plates increase the vertical stability to the
      osteosynthesis. Fracture fixation of the anterior ring follows the dorsal
      procedure. POSTOPERATIVE MANAGEMENT: The patient is mobilized with partial weight
      bearing. Clinical and radiological follow-up is planned after 6 and 12 weeks.
      RESULTS: A total of 27 patients with vertical unstable pelvic fractures were
      identified and treated with open reduction and double-plate osteosynthesis. The
      Iowa pelvic score was rated excellent in 83 % and good in 17 % of cases. One
      patient developed a nonunion and had to be revised.

PMID- 25395054
TI  - Expression patterns of dishevelled-2 in different colon tissue segments in
      Hirschsprung's disease.
AB  - Hirschsprung's disease (HSCR) is a congenital disorder characterized by an
      absence of enteric ganglion cells in the terminal regions of the gut during
      development. To date, the cause of HSCR remains unclear, although the
      pathogenesis of this complex disease is hypothesized to be influenced by numerous
      genetic and environmental factors. Dishevelled-2 (DVL-2) is a subtype of the
      dishevelled protein, which is known to be involved in embryonic development. In
      the present study, the pathogenesis of HSCR was investigated by measuring the
      expression of the DVL-2 gene and protein using reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry
      staining in the aganglionic and ganglionic segments of colonic tissues in
      patients with HSCR. The results showed that the level of DVL-2 mRNA in the
      aganglionic segments was 0.28 fold that of the ganglionic segments. Similarly,
      the protein expression of DVL-2 was lower (11.31+/-2.23) in the aganglionic
      segments than that of the ganglionic segments (35.21+/-2.66), as assessed by
      western blot analysis. Furthermore, immunohistochemical staining demonstrated
      that DVL-2 expression was significantly higher in the mucosal and submucosal
      layers from ganglionic colon segments compared with that from the aganglionic
      segments. The data suggest that the expression of DVL-2 in colon tissue segments
      may be important in the pathogenesis of HSCR.

PMID- 25395053
TI  - Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops.
AB  - Hypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in
      the conformational transition of Env to the receptor binding-induced metastable
      state. Structural analysis of full-length Env-based immunogens, containing the
      entire V2 loop, displayed tighter association between gp120 subunits, resulting
      in a smaller trimeric diameter than constructs lacking V2. A prominent basal
      quaternary location of V2 and V3' that challenges previous reports would
      facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary
      mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2
      resulted in dramatic exposure of basal, membrane-proximal gp41 epitopes,
      consistent with its predicted basal location. The structural features of HIV-1
      Env characterized here provide grounds for a paradigm shift in loop exposure and
      epitope occlusion, while providing substantive rationale for epitope display
      required for elicitation of broadly neutralizing antibodies, as well as
      substantiating previous pertinent literature disregarded in recent reports. 

PMID- 25395055
TI  - Bioinspired copper(I) complexes that exhibit monooxygenase and catechol
      dioxygenase activity.
AB  - New tripodal ligand L2 featuring three different pyridyl/imidazolyl-based N-donor
      units at a bridgehead C atom, from which one of the imidazolyl units is separated
      by a phenylene linker, was synthesized and investigated with regards to copper(I)
      complexation. The resulting complex [(L2)Cu]OTf (2(OTf)), the known complex
      [(L1)Cu]OTf (1(OTf); L1 differs from L2 in that it lacks the phenylene spacer)
      and [(L3)Cu]OTf (3(OTf)), prepared from a known chiral, tripodal, N-donor ligand
      featuring pyridyl, pyrazolyl, and imidazolyl donors, were tested as catalysts for
      the oxidation of sodium 2,4-di-tert-butylphenolate (NaDTBP) with O2. Indeed, they
      mediated NaDTBP oxidation to give mainly the corresponding catecholate and
      quinone (Q). None of the complexes 1(OTf), 2(OTf), and 3(OTf) is superior to the
      others, as yields were comparable and, if the presence of protons is guaranteed
      by concomitant addition of the phenol DTBP, the oxidation can also be performed
      catalytically. For all complexes stoichiometric oxidations under certain
      conditions (concentrated solutions, high NaDTBP content) were found to also
      generate products typical for metal-mediated intradiol cleavage of the
      catecholate with O2. As shown representatively for 1(OTf) this dioxygenation sets
      in at a later stage of the reaction. Initially a copper species responsible for
      the monooxygenation must form from 1(OTf)/NaDTBP/O2, and only thereafter is the
      copper species responsible for dioxygenation formed and consumes Q as substrate.
      Hence, under these circumstances complexes 1(OTf)-3(OTf) show both monooxygenase
      and catechol dioxygenase activity.

PMID- 25395056
TI  - Medicaid managed care: how to target efforts to reduce costs.
AB  - BACKGROUND: To be successful, cost control efforts must target Medicaid Managed
      Care (MMC) beneficiaries likely to incur high costs. The critical question is how
      to identify potential high cost beneficiaries with simple, reproducible,
      transparent, auditable criteria. Our objective in this analysis was to evaluate
      whether the total burden of comorbidity, assessed by the Charlson comorbidity
      index, could identify MMC beneficiaries who incurred high health care costs.
      METHODS: The MetroPlus MMC claims database was use to analyze six months of
      claims data from 07/07-12/07; the analysis focused on the total amount paid. Age,
      gender, Charlson comorbidity score, serious mental illness and pregnancy were
      analyzed as predictors of total costs. RESULTS: We evaluated the cost profile of
      4,614 beneficiaries enrolled at MetroPlus, an MMC plan. As hypothesized, the
      comorbidity index was a key correlate of total costs (p < .01). Yearly costs were
      more related to the total burden of comorbidity than any specific comorbid
      disease. For adults, in addition to comorbidity (p < .01) both serious mental
      illness (p < .01) and pregnancy (p < .01) were also related to total costs, while
      age, drug addiction and gender were not. The model with age, gender, comorbidity,
      serious mental illness, pregnancy and addiction explained 20% of the variance in
      total costs. In children, comorbidity (p < .01), serious mental illness (p <
      .01), addiction (p < .03) and pregnancy (p < .01) were associated with log cost;
      the model with those variables explained 6% of the variance in costs.
      CONCLUSIONS: Comorbidity can be used to identify MMC beneficiaries most likely to
      have high costs.

PMID- 25395057
TI  - Evaluation of a community-academic partnership: lessons from Latinos in a network
      for cancer control.
AB  - Established in 2002, Latinos in a Network for Cancer Control is a community
      academic network supported by the Centers for Disease Control and Prevention and
      the National Cancer Institute. The network includes >130 individuals from 65
      community and academic organizations committed to reducing cancer-related health
      disparities. Using an empirically derived systems model--the Bergen Model of
      Collaborative Functioning--as the analytic frame, we interviewed 19 partners to
      identify challenges and successful processes. Findings indicated that sustained
      partner interaction created "meaningful relationships" that were routinely called
      on for collaboration. The leadership was regarded positively on vision, charisma,
      and capacity. Limitations included overreliance on a single leader. Suggestions
      supported more delegation of decision making, consistent communication, and more
      equitable resource distribution. The study highlighted new insights into dynamics
      of collaboration: Greater inclusiveness of inputs (partners, finances, mission)
      and loosely defined roles and structure produced strong connections but less
      network-wide productivity (output). Still, this profile enabled the creation of
      more tightly defined and highly productive subgroups, with clear goals and roles
      but less inclusive of inputs than the larger network. Important network outputs
      included practice-based research publications, cancer control intervention
      materials, and training to enhance the use of evidence-based interventions, as
      well as continued and diversified funding.

PMID- 25395059
TI  - Gene encoding inulinase isolated from Penicillium citrinum ESS and its molecular
      phylogeny.
AB  - Inulinase is an enzyme produced by plants and several microorganisms, including
      fungi, to hydrolyze the beta-2,1 glycosidic linkages present in some
      oligosaccharides to produce fructose and glucose. This enzyme, in conjunction
      with invertases, levanases, and two types of 1-fructosyl transferases have been
      described as members of the glycosyl hydrolases (family 32), the most diverse
      group of enzymes used by microbes for biomass degradation. As being part of the
      same clan, they have common evolutionary origin sharing the most important
      functional characteristics. Recently, a xerophylic fungi strain isolated from
      Mexican semi-desert, Penicillium citrinum ESS has been reported as inulinase
      producer, which could have greater stability than other enzymes due to a
      metabolic machinery adapted to typical temperature changes in this region. To
      continue the understanding of action mechanisms of these enzymes and to establish
      evolutionary relationships within this family, in the present study, phylogenetic
      analyses were used to analyze amino acid sequences coding fungal and yeast
      glycoside hydrolases of family 32, including the new sequenced inulinase of P.
      citrinum ESS. It was possible to elucidate the action mechanism of fungal
      glycoside hydrolases in present study and to classify inulinase from P. citrinum
      ESS as an exo-inulinase on the basis of their amino acid sequence phylogenetic
      affinities.

PMID- 25395058
TI  - Regional cerebellar volume and cognitive function from adolescence to late middle
      age.
AB  - Cerebellar morphology and function have been implicated in a variety of
      developmental disorders, and in healthy aging. Although recent work has sought to
      characterize the relationships between volume and age in this structure during
      adolescence, young, and older adulthood, there have been no investigations of
      regional cerebellar volume from adolescence through late middle age. Middle age
      in particular has been largely understudied, and investigating this period of the
      lifespan may be especially important for our understanding of senescence.
      Understanding regional patterns of cerebellar volume with respect to age during
      this portion of the lifespan may provide important insight into healthy aging and
      cognitive function as well as pathology from adolescence into later life. We
      investigated regional cerebellar volume using a highly novel lobular segmentation
      approach in conjunction with a battery of cognitive tasks in a cross-sectional
      sample of 123 individuals from 12 to 65 years old. Our results indicated that
      regional cerebellar volumes show different patterns with respect to age. In
      particular, the more posterior aspect of the neocerebellum follows a quadratic
      "inverse-U" pattern while the vermis and anterior cerebellum follow logarithmic
      patterns. In addition, we quantified the relationships between age and a variety
      of cognitive assessments and found relationships between regional cerebellar
      volumes and performance. Finally, exploratory analyses of sex differences in the
      relationships between regional cerebellar volume, age, and cognition were
      investigated. Taken together, these results provide key insights into the
      development and aging of the human cerebellum, and its role in cognitive function
      across the lifespan.

PMID- 25395061
TI  - Ethical Study on the Reform and Development of Medical and Health Services in
      China.
AB  - At an early stage of its foundation, new China became clear about the nature of
      public welfare and quickly developed medical and health services, which was well
      received by the World Health Organization. The marketization and the reduction of
      input into medical and health services from the 1980s created severe adverse
      consequences. After the SARS' outbreak in 2003, China started to give serious
      consideration to its medical and health system, and to work at developing medical
      and health services. The new healthcare reform launched in 2009 re-emphasizes
      fairness and public welfare, and China's achievements have been remarkable. Of
      course, there are still many problems to be solved in the reform, which also
      paves the way for increasing the reform in future. 

PMID- 25395060
TI  - Comparative effects of pulmonary and parenteral Delta9-tetrahydrocannabinol
      exposure on extinction of opiate-induced conditioned aversion in rats.
AB  - RATIONALE: Evidence suggesting that the endogenous cannabinoid (eCB) system can
      be manipulated to facilitate or impair extinction of learned behaviours has
      important consequences for opiate withdrawal and abstinence. We demonstrated that
      the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases eCB
      levels, facilitates extinction of a naloxone-precipitated morphine withdrawal
      induced conditioned place aversion (CPA). OBJECTIVES: The potential of the
      exogenous CB1 ligand, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), to facilitate
      extinction of this CPA was tested. Effects of both pulmonary and parenteral
      Delta(9)-THC exposure were evaluated using comparable doses previously
      determined. METHODS: Rats trained to associate a naloxone-precipitated morphine
      withdrawal with a floor cue were administered Delta(9)-THC-pulmonary (1, 5, 10 mg
      vapour inhalation) or parenteral (0.5, 1.0, 1.5 mg/kg intraperitoneal injection)
      prior to each of 20 to 28 extinction/testing trials. RESULTS: Vapourized Delta(9)
      THC facilitated extinction of the CPA in a dose- and time-dependent manner: 5 and
      10 mg facilitated extinction compared to vehicle and 1 mg Delta(9)-THC. Injected
      Delta(9)-THC significantly impaired extinction only for the 1.0-mg/kg dose: it
      prolonged the CPA fourfold longer than the vehicle and 0.5- and 1.5-mg/kg doses.
      CONCLUSIONS: These data suggest that both dose and route of Delta(9)-THC
      administration have important consequences for its pharmacokinetic and
      behavioural effects; specifically, pulmonary exposure at higher doses
      facilitates, whereas pulmonary and parenteral exposure at lower doses impairs,
      rates of extinction learning for CPA. Pulmonary-administered Delta(9)-THC may
      prove beneficial for potentiation of extinction learning for aversive memories,
      such as those supporting drug-craving/seeking in opiate withdrawal syndrome, and
      other causes of conditioned aversions, such as illness and stress.

PMID- 25395062
TI  - Alveolar bone loss and ageing: possible association with coronary heart diseases
      and/or severe vascular diseases.
AB  - OBJECTIVE: The objective of this study was to utilise a new methodological
      approach based on radiographic examinations to demonstrate a potential
      association between coronary heart diseases (CHD) as well as severe hypertension
      and alveolar bone loss (ABL) in older adults. BACKGROUND: Many studies, primarily
      assessing clinical parameters, underline the association between periodontal
      diseases and cardiovascular diseases. The relationship between ABL and
      CHD/vascular diseases (VD) is potentially of high importance because of their
      prevalence in populations, and they represent an important issue in the fields of
      epidemiology and public health. Therefore, this topic was approached with new
      tools. MATERIALS AND METHODS: The study was comprised of 236 participants over 50
      years. A clinical examination and a radiographic assessment of ABL were
      performed. Direct measures of alveolar bone level were recorded using CT scans,
      and different variables were studied (age, sex, Plaque index, cigarettes per day,
      coronary heart disease and vascular disease status). A medical examination report
      was attached to the investigation file. RESULTS: The results confirmed a positive
      association between CHD/VD and periodontal destruction; alveolar bone destruction
      represented a risk factor for CHD/VD [odds ratio (OR): 1.27; 95% CI: 1.01-1.60; p
      < 0.037]. CONCLUSION: This study supports an association between periodontal
      diseases and CHD/VD independent of known confounders, although an aetiological
      link of causality has not been established.

PMID- 25395063
TI  - A fully validated method for the determination of lacosamide in human plasma
      using gas chromatography with mass spectrometry: application for therapeutic drug
      monitoring.
AB  - A simple gas chromatographic method with mass spectrometry detection was
      developed and validated for the determination of lacosamide in human plasma.
      Lacosamide and the internal standard, levetiracetam-d6, were extracted from 200
      MUL plasma, by a solid-phase extraction through HF Bond Elut C18 columns, and
      derivatized using N-methyl-N-tert-butyldimethylsilyltrifluoroacetamide with 1%
      tert-butyldimethylsilylchloride in acetonitrile. The limit of quantification was
      found to be 0.20 MUg/mL and the assay was linear up to 20.0 MUg/mL with
      correlation coefficient >=0.994. The intra- and interday precision values were
      <4.1% in terms of relative standard deviation (%) and the values of intra- and
      interday accuracy were found to be within -7.2 and 5.3% in terms of relative
      error (%). Absolute recovery of the method for lacosamide was determined at three
      concentration levels and ranged from 92.5 to 97.6%. The developed method uses
      small volumes of plasma and proved to be simple, rapid, and sensitive for the
      determination of lacosamide in plasma. This method can be used in routine every
      day analysis of plasma samples obtained from patients who follow respective
      antiepileptic treatment and for the investigation of clinical and forensic cases
      where lacosamide is involved.

PMID- 25395064
TI  - Simple and efficient separation of atomically precise noble metal clusters.
AB  - There is an urgent need for accessible purification and separation strategies of
      atomically precise metal clusters in order to promote the study of their
      fundamental properties. Although the separation of mixtures of atomically precise
      gold clusters Au25L18, where L are thiolates, has been demonstrated by advanced
      separation techniques, we present here the first separation of metal clusters by
      thin-layer chromatography (TLC), which is simple yet surprisingly efficient. This
      method was successfully applied to a binary mixture of Au25L18 with different
      ligands, as well as to a binary mixture of different cluster cores, Au25 and
      Au144, protected with the same ligand. Importantly, TLC even enabled the
      challenging separation of a multicomponent mixture of mixed-monolayer-protected
      Au25 clusters with closely similar chemical ligand compositions. We anticipate
      that the realization of such simple yet efficient separation technique will
      progress the detailed investigation of cluster properties. 

PMID- 25395065
TI  - Characterizing the contrast of white matter and grey matter in high-resolution
      phase difference enhanced imaging of human brain at 3.0 T.
AB  - OBJECTIVES: The purpose of this study was to address the feasibility of
      characterizing the contrast both between and within grey matter and white matter
      using the phase difference enhanced (PADRE) technique. METHODS: PADRE imaging was
      performed in 33 healthy volunteers. Vessel enhancement (VE), tissue enhancement
      (TE), and PADRE images were reconstructed from source images and were evaluated
      with regard to differentiation of grey-to-white matter interface, the stria of
      Gennari, and the two layers, internal sagittal stratum (ISS) and external
      sagittal stratum (ESS), of optic radiation. RESULTS: White matter regions showed
      decreased signal intensity compared to grey matter regions. Discrimination was
      sharper between white matter and cortical grey matter in TE images than in PADRE
      images, but was poorly displayed in VE images. The stria of Gennari was observed
      on all three image sets. Low-signal-intensity bands displayed in VE images
      representing the optic radiation were delineated as two layers of different
      signal intensities in TE and PADRE images. Statistically significant differences
      in phase shifts were found between frontal grey and white matter, as well as
      between ISS and ESS (p < 0.01). CONCLUSIONS: The PADRE technique is capable of
      identifying grey-to-white matter interface, the stria of Gennari, and ISS and
      ESS, with improved contrast in PADRE and TE images compared to VE images. KEY
      POINTS: * Phase difference enhanced (PADRE) imaging can yield diverse contrasts
      between tissues * The PADRE technique utilizes the inherent variety of magnetic
      susceptibilities * PADRE MR imaging provides better visualization of certain
      cerebral anatomy in vivo * PADRE imaging is able to delineate the stria of
      Gennari in the primary visual cortex * PADRE imaging is able to identify the two
      optic radiation layers.

PMID- 25395066
TI  - Comparison of two fat-suppressed magnetic resonance imaging pulse sequences to
      standard t2-weighted images for brain parenchymal contrast and lesion detection
      in dogs with inflammatory intracranial disease.
AB  - T2-weighted (T2w) sequences are commonly relied upon in magnetic resonance
      imaging protocols for the detection of brain lesions in dogs. Previously, the
      effect of fluid suppression via fluid-attenuated inversion recovery (FLAIR) has
      been compared to T2-weighting with mixed results. Short tau inversion recovery
      (STIR) has been reported to increase the detection of some CNS lesions in people.
      The purpose of the current study was to evaluate the effect of fat suppression on
      brain parenchymal contrast resolution and lesion detection in dogs. We compared
      three sequences: T2w images, STIR, and T2w FLAIR with chemical fat suppression
      (T2-FLAIR-FS) in dogs with meningoencephalitis. Dogs with meningoencephalitis and
      dogs with idiopathic epilepsy were retrospectively identified and anonymized.
      Evaluators recorded the presence or absence of lesions within 12 predetermined
      brain regions on randomized sequences, viewing and scoring each sequence
      individually. Additionally, signal-to-noise ratios, contrast-to-noise ratios, and
      relative contrast (RC) were measured in a reference population. Short tau
      inversion recovery sequences had the highest RC between gray and white matter.
      While descriptively more lesions were identified by evaluators on T2-FLAIR-FS
      images, there was no statistical difference in the relative sensitivity of lesion
      detection between the sequences. Nor was there a statistical difference in false
      lesion detection within our reference population. Short tau inversion recovery
      may be favored for enhanced anatomic contrast depiction in brain imaging. No
      benefit of the inclusion of a fat-suppressed T2-FLAIR sequence was found. 

PMID- 25395068
TI  - Using an international p53 mutation database as a foundation for an online
      laboratory in an upper level undergraduate biology class.
AB  - A two-part laboratory exercise was developed to enhance classroom instruction on
      the significance of p53 mutations in cancer development. Students were asked to
      mine key information from an international database of p53 genetic changes
      related to cancer, the IARC TP53 database. Using this database, students designed
      several data mining activities to look at the changes in the p53 gene from a
      number of perspectives, including potential cancer-causing agents leading to
      particular changes and the prevalence of certain p53 variations in certain
      cancers. In addition, students gained a global perspective on cancer prevalence
      in different parts of the world. Students learned how to use the database in the
      first part of the exercise, and then used that knowledge to search particular
      cancers and cancer-causing agents of their choosing in the second part of the
      exercise. Students also connected the information gathered from the p53 exercise
      to a previous laboratory exercise looking at risk factors for cancer development.
      The goal of the experience was to increase student knowledge of the link between
      p53 genetic variation and cancer. Students also were able to walk a similar path
      through the website as a cancer researcher using the database to enhance bench
      work-based experiments with complementary large-scale database p53 variation
      information.

PMID- 25395067
TI  - Annexin A10 is a marker for the serrated pathway of colorectal carcinoma.
AB  - Serrated adenocarcinoma (SAC), representing at least 10 % of colorectal
      carcinomas (CRC), differs from conventional carcinomas not only by its histology,
      but also by its molecular basis. However, the diagnosis of SAC in poorly
      differentiated cases and without an adjacent serrated adenoma can be challenging.
      In this study, we utilized previously described expression data and identified
      annexin A10 (ANXA10) as a potential marker for SAC. We conducted ANXA10
      immunohistochemistry in groups of 146 CRC patients and 131 serrated and
      conventional polyps. In CRC cases, ANXA10 expression associated with serrated
      histology (sensitivity 42 % and specificity 98 %). BRAF V600E mutation correlated
      with ANXA10 expression but also seven BRAF wild-type tumors (5 %) were positive
      for ANXA10. Immunoreactivity for either ANXA10 or BRAF V600E was an accurate
      predictor of serrated histology (sensitivity 55 % and specificity 97 %). ANXA10
      expression did not associate with tumor stage or grade. Of the 131 colorectal
      polyps, 30/30 of sessile serrated adenomas, 6/11 traditional serrated adenomas,
      20/32 hyperplastic polyps, and 2/27 tubulovillous adenomas were positive for
      ANXA10, while 31/31 tubular adenomas were negative. In conclusion, the results
      suggest that ANXA10 is a marker with high specificity for the serrated pathway of
      CRC.

PMID- 25395069
TI  - Effects of root canal preparation, various filling techniques and retreatment
      after filling on vertical root fracture and crack formation.
AB  - AIM: To investigate the incidence of cracks in root dentin after rotary
      instrumentation and filling with cold lateral condensation (CL), single-cone
      obturation (SC), and warm vertical compaction (WV) and retreatment of each
      filling system. METHODOLOGY: One-hundred sixty mandibular incisors were selected.
      Twenty teeth were left unprepared and served as a control, and the remaining 140
      teeth were instrumented. Twenty teeth were assigned to an only prepared group.
      The remaining 120 teeth were assigned to three root canal filling groups and
      three retreatment groups (n = 20), as follows: CL, WV, SC, and retreatment of
      each filling system. All the roots were sectioned perpendicular to the long axis
      at 2, 4, 6, and 8 mm from the apex, and the sections were then observed under a
      stereomicroscope. The absence/presence of cracks and vertical root fractures were
      recorded, and the data were analyzed with a Pearson's chi-square test (P = 0.05).
      RESULTS: No complete vertical root fractures were observed in the unprepared and
      only prepared groups. However, vertical fractures were observed in the filling
      and retreatment groups. There were significantly more cracks in the retreatment
      after WV group than the other groups, with the exception of the retreatment after
      SC, WV, and CL resulted in significantly more cracks than the only prepared and
      SC. CONCLUSIONS: The filling techniques (except SC) caused more cracks than
      preparation only. The SC caused fewer cracks compared to the other filling
      techniques. The retreatment following the different filling techniques (except
      CL) caused more cracks than the original fillings.

PMID- 25395071
TI  - Circulating semaphorin-4D and plexin-B1 levels in postmenopausal women with low
      bone mass: the 3-month effect of zoledronic acid, denosumab or teriparatide
      treatment.
AB  - OBJECTIVE: The evaluation of circulating semaphorin-4D (sema4D) and plexin-B1 in
      postmenopausal women with low bone mass and the effect of antiresorptive or
      osteoanabolic treatment. METHODS: Serum samples were obtained from postmenopausal
      women with low bone mass at baseline and 3 months after zoledronic acid infusion
      (n = 30), denosumab injection (n = 30) or teriparatide initiation (n = 28) and
      from controls matched for age, age at menopause and body mass index (n = 30) at
      the same time points. MAIN OUTCOME MEASURES: Circulating sema4D and plexin-B1.
      RESULTS: Circulating sema4D increased following denosumab (p = 0.026), whereas
      decreased following teriparatide (p = 0.013). Sema4D/plexin-B1 ratio increased
      following denosumab (p = 0.004). At baseline, sema4D and plexin-B1 levels were
      higher in patients pre-treated with bisphosphonates compared to naive ones (p <
      0.001 and p = 0.001, respectively). In bivariate correlations sema4D was
      inversely correlated with serum carboxyterminal telopeptide of type 1 collagen
      (rs -0.282, p = 0.002), intact parathyroid hormone (rs -0.388, p < 0.001) and
      25(OH)D (rs -0.316, p < 0.001), whereas there was a trend towards correlation
      with lumbar spine bone mineral density (rs -0.191, p = 0.053). CONCLUSIONS:
      Sema4D levels are independently associated with previous bisphosphonate
      treatment, intact parathyroid hormone and 25(OH)D levels. Denosumab and
      teriparatide seem to exert an opposite effect on circulating sema4D levels.
      Further studies are needed to evaluate whether sema4D mediates the coupling
      effect that occurs following both antiresorptive and osteoanabolic treatment.

PMID- 25395070
TI  - Acetone-butanol-ethanol competitive sorption simulation from single, binary, and
      ternary systems in a fixed-bed of KA-I resin.
AB  - Separation of butanol based on sorption methodology from acetone-butanol-ethanol
      (ABE) fermentation broth has advantages in terms of biocompatibility and
      stability, as well as economy, and therefore gains much attention. In this work a
      chromatographic column model based on the solid film linear driving force
      approach and the competitive Langmuir isotherm equations was used to predict the
      competitive sorption behaviors of ABE single, binary, and ternary mixture. It was
      observed that the outlet concentration of weaker retained components exceeded the
      inlet concentration, which is an evidence of competitive adsorption. Butanol, the
      strongest retained component, could replace ethanol almost completely and also
      most of acetone. In the end of this work, the proposed model was validated by
      comparison of the experimental and predicted ABE ternary breakthrough curves
      using the real ABE fermentation broth as a feed solution.

PMID- 25395072
TI  - Case report: Hyperthermia and diminished consciousness in an elderly woman
      following an accidental overdose of scopolamine.

PMID- 25395073
TI  - Downregulation of c-Met expression does not enhance the sensitivity of gastric
      cancer cell line MKN-45 to gefitinib.
AB  - The aim of the present study was to investigate the effect of downregulation of
      the c-Met gene on signal transduction and apoptosis in gastric cancer MKN-45
      cells; furthermore, the study aimed to determine whether altered c-Met gene
      expression affected MKN-45 sensitivity to gefitinib. Three c-Met-specific small
      interfering RNAs (siRNAs) were synthesized and transfected into MKN-45 cells.
      Messenger RNA (mRNA) and protein levels of c-Met and its downstream signaling
      molecules [phosphoinositide 3-kinase (PI3K) and AKT] were examined using reverse
      transcription polymerase chain reaction and western blot analysis 48 h following
      transfection. Cell apoptosis was evaluated using Annexin-V/propidium iodide
      double staining and fluorescence-activated cell sorting analysis. An MTT assay
      was performed in order to measure the 50% inhibitory concentration (IC50) of
      gefitinib on MKN-45 cells. The results of the present study demonstrated that 48
      h post-transfection with c-Met siRNA, MKN-45 cells showed significantly
      downregulated expression of c-Met mRNA and protein as well as an increased rate
      of apoptosis (P<0.05). In addition, following c-Met siRNA transfection mRNA and
      protein levels of PI3K and AKT were not significantly altered in MKN-45 cells
      (P>0.05); however, a marked decrease in the expression levels of phosphorylated
      (p)-PI3K and p-AKT was observed (P<0.05). Furthermore, the IC50 of gefitinib in
      MKN-45 cells was not significantly decreased. In conclusion, knockdown of the c
      Met gene promoted gastric cancer cell apoptosis and inhibited downstream p-PI3K
      and p-AKT; however, the sensitivity of MKN-45 cells to gefitinib was not
      increased.

PMID- 25395074
TI  - Proteome profiling of keratinocytes transforming to malignancy.
AB  - To shed light on the multistep process of squamous cell carcinoma development and
      the underlying pathologic mechanisms, we performed comparative proteome analysis
      of keratinocytes, keratinocytes stimulated with Il-1beta, and A431 epidermoid
      carcinoma cells. Fractionation of the cells into supernatant, nucleus, and
      cytoplasm was followed by protein separation, proteolytic digest, and nano-LC
      separation, and fragmentation using an ion trap mass spectrometer. Specific
      bioinformatics tools were used to generate a list of keratinocyte-specific
      proteins. Ninety percent of these proteins were found to be upregulated in
      keratinocytes versus the A431 cells. Classification of the identified proteins by
      biologic function and gene set enrichment analysis revealed that keratinocytes
      produced more proteins involved in cell differentiation, cell adhesion, cell
      junction, calcium ion, calmodulin binding, cytoskeleton organization, and
      cytokinesis, whereas A431 produced more proteins involved in cell cycle
      checkpoint, cell cycle process, RNA processing and transport, DNA damage and
      repair, RNA and DNA binding, and chromatin remodeling. The protein signatures of
      A431 and normal keratinocytes treated with IL-1beta showed marked similarity,
      confirming that inflammation is an important step in malignant transformation in
      nonmelanoma skin cancer. Thus, proteome profiling and bioinformatic processing
      may support the understanding of the underlying mechanisms, with the potential to
      facilitate development of early biomarkers and patient-tailored therapy. 

PMID- 25395075
TI  - Meta-analysis of emotion recognition deficits in major depressive disorder.
AB  - BACKGROUND: Many studies have explored associations between depression and facial
      emotion recognition (ER). However, these studies have used various paradigms and
      multiple stimulus sets, rendering comparisons difficult. Few studies have
      attempted to determine the magnitude of any effect and whether studies are
      properly powered to detect it. We conducted a meta-analysis to synthesize the
      findings across studies on ER in depressed individuals compared to controls.
      METHOD: Studies of ER that included depressed and control samples and published
      before June 2013 were identified in PubMed and Web of Science. Studies using
      schematic faces, neuroimaging studies and drug treatment studies were excluded.
      RESULTS: Meta-analysis of k = 22 independent samples indicated impaired
      recognition of emotion [k = 22, g = -0.16, 95% confidence interval (CI) -0.25 to 
      0.07, p < 0.001]. Critically, this was observed for anger, disgust, fear,
      happiness and surprise (k's = 7-22, g's = -0.42 to -0.17, p's < 0.08), but not
      sadness (k = 21, g = -0.09, 95% CI -0.23 to +0.06, p = 0.23). Study-level
      characteristics did not appear to be associated with the observed effect. Power
      analysis indicated that a sample of approximately 615 cases and 615 controls
      would be required to detect this association with 80% power at an alpha level of
      0.05. CONCLUSIONS: These findings suggest that the ER impairment reported in the
      depression literature exists across all basic emotions except sadness. The effect
      size, however, is small, and previous studies have been underpowered.

PMID- 25395078
TI  - The placement of peritoneal dialysis catheters: a prospective randomized
      comparison of open surgery versus "Mini-Perc" technique.
AB  - PURPOSE: Currently, most ESRD patients are treated with open surgical technique
      or with laparoscopic technique. In this study, we examined the role of the
      ureteroscope-assisted "Mini-Perc" technique versus the modified open surgery in
      the treatment of ESRD in a prospective randomized manner. METHODS: A total of 72
      patients with chronic renal failure were prospectively randomized for the
      ureteroscope-assisted "Mini-Perc" technique or modified open surgery.
      Intraoperative and postoperative morbidity, incision size, dose of local
      anesthesia, operative time, hospital stay, and initial catheter survival and
      follow-up were compared for both methods. RESULTS: "Mini-Perc" group was
      associated with shorter incision size, operative time, and hospital stay, with
      lower dose of local anesthesia and incidence of bloody ascites. Two of five
      patients with the history of abdominal surgery in "Mini-Perc" group required
      adhesiolysis under direct vision of telescope. All adhesions were easily
      dissected. All complications of leakage (8.1 %) and incisional hernia (2.7 %)
      occurred in the open surgery group, but a difference of no significant value with
      "Mini-Perc" group (p = 0.2400, p = 1.0000). There was no any other significant
      difference in common complications between two groups. After 2 years of follow
      up, 54 patients (75 %) survived with their initial PD catheter. The overall death
      was 5 (6.9 %). CONCLUSIONS: Compared to modified open surgical technique, the
      ureteroscope-assisted "Mini-Perc" technique can be used to achieve the same
      clinical efficacy for placement of peritoneal dialysis catheters in ESRD
      patients, and it carries minimal morbidity.

PMID- 25395080
TI  - Complete mitochondrial genome of Coregonus peled.
AB  - The complete mitochondrial genome of Coregonus peled is determined in this study.
      The mitogenome is 16,736 bp in length and contains 1D-loop region, 2 ribosomal
      RNA genes, 22 transfer RNA genes and 13 protein-coding genes. The overall base
      composition of the heavy strand is 26.76% for A, 29.45% for C, 18.10% for G and
      25.67% for T. The percentage of G + C content is 47.55 %. This is the first time
      of the mitochondrial genome sequencing for Coregonus peled.

PMID- 25395081
TI  - The mitochondrial genome of the hammerhead Sphyrna zygaena.
AB  - The hammerhead shark (Sphyrna zygaena) is listed as a "Vulnerable" species for
      the International Union for Conservation of Nature (IUCN). Here we report the
      complete sequence for the mitochondrial genome of the hammerhead shark of a
      specimen collected from the eastern Pacific Ocean. The genome structure is quite
      similar to other reported mtDNA shark species. It has a total length of 16,731
      base pairs (bp); the base composition was A (31.54%), T (30.23%) C (25.03%) and
      G: 13.20, contains 13 protein-coding genes, 2 rRNA genes; 21 tRNA genes. In
      addition, most of the starting (ATG) and ending codons (TAA) for the mtDNA gene
      regions were registered.

PMID- 25395082
TI  - The structure of apo-kinesin bound to tubulin links the nucleotide cycle to
      movement.
AB  - Kinesin-1 is a dimeric ATP-dependent motor protein that moves towards
      microtubules (+) ends. This movement is driven by two conformations (docked and
      undocked) of the two motor domains carboxy-terminal peptides (named neck
      linkers), in correlation with the nucleotide bound to each motor domain. Despite
      extensive data on kinesin-1, the structural connection between its nucleotide
      cycle and movement has remained elusive, mostly because the structure of the
      critical tubulin-bound apo-kinesin state was unknown. Here we report the 2.2 A
      structure of this complex. From its comparison with detached kinesin-ADP and
      tubulin-bound kinesin-ATP, we identify three kinesin motor subdomains that move
      rigidly along the nucleotide cycle. Our data reveal how these subdomains reorient
      on binding to tubulin and when ATP binds, leading respectively to ADP release and
      to neck linker docking. These results establish a framework for understanding the
      transformation of chemical energy into mechanical work by (+) end-directed
      kinesins.

PMID- 25395083
TI  - Swedish National Penile Cancer Register: incidence, tumour characteristics,
      management and survival.
AB  - OBJECTIVES: To assess penile cancer incidence, stage distribution, adherence to
      guidelines and prognostic factors in a population-based setting. PATIENTS AND
      METHODS: The population-based Swedish National Penile Cancer Register (NPECR)
      contains detailed information on tumour characteristics and management patterns.
      A total of 1 678 men with primary squamous cell carcinoma of the penis identified
      in the NPECR between 2000 and 2012 were included in the study. RESULTS: The mean
      age-adjusted incidence of penile cancer was 2.1/100 000 men, remaining virtually
      unchanged during the study period. At diagnosis, 14 and 2% of the men had
      clinical N+ and M+ disease, respectively. Most men were staged pTis (34%), pT2
      (19%), or pT1 (18%), while stage information was unavailable for 18% of the men.
      Organ-preserving treatment was used in 71% of Tis-T1 tumours. Of men with cN0 and
      >=pT1G2 disease, 50% underwent lymph node staging, while 74% of men with cN1-3
      disease underwent lymph node dissection. The overall 5-year relative survival
      rate was 82%. Men aged >=40 years and those with pT2-3, G2-3 and N+ tumours had
      worse outcomes. CONCLUSIONS: The incidence of penile cancer in Sweden is stable.
      Most men presented with localized disease, and the proportion of non-invasive
      tumours was high. During the period under study, adherence to guidelines was
      suboptimum. The overall 5-year relative survival rate was 82%. Older age,
      increasing tumour stage and grade, and increasing lymph node stage were
      associated with poorer survival.

PMID- 25395085
TI  - Intraoperative platelet transfusion is associated with increased postoperative
      sternal wound infections among type A aortic dissection patients after total arch
      replacement.
AB  - BACKGROUND: Blood transfusion and its impact upon clinical outcomes of cardiac
      surgery have been extensively discussed, especially in the post-aprotinin era.
      This study compared clinical outcomes and perioperative blood utilisation among
      acute type A aortic dissection (AAD) patients with or without intraoperative
      platelet transfusion during total arch replacement, thus intending to investigate
      prognostic value of platelet transfusion during major aortic surgeries. MATERIALS
      AND METHODS: Acute AAD patients undergoing total arch replacement and stented
      elephant trunk procedure under hypothermic circulatory arrest with and without
      intraoperative platelet transfusion at our institute from January 2008 to
      December 2012 were retrospectively included. Patients were categorised into PLT
      (n = 74) and non-PLT (n = 85) groups to compare the in-hospital mortality and
      complications, as well as blood components utilisation. RESULTS: Baseline
      characteristics and operational features were all comparable between two groups.
      In PLT group, in-hospital survival was not improved and intraoperative
      utilisation of red blood cell RBC, fresh frozen plasma (FFP) and cryoprecipitate
      was not reduced. Postoperative RBC transfusion [2.0(0-4.0) vs 0(0-4.0) U, p =
      0.026; 64.9 vs 43.5%, p = 0.007] was significantly increased in PLT group,
      parallel with the prolonged postoperative hospitalisation time [(24.0 +/- 12.7)
      vs (20.8 +/- 10.9) days, p = 0.093] and elevated incidence of sternal wound
      infections (16.2 vs 5.9%, p = 0.035). Intraoperative platelet transfusion [odds
      ratio (OR): 3.10, 95% confidence interval (CI): 1.04-9.25, p = 0.043] was
      identified as independent risk factor of postoperative sternal wound infections
      by multivariate logistic regression analysis. CONCLUSION: Intraoperative platelet
      transfusion did not improve in-hospital prognosis among AAD patients after total
      arch replacement. The incidence of postoperative sternal wound infections
      increased among those who received intraoperative platelet transfusion.

PMID- 25395084
TI  - SEPP1 gene variants and abdominal aortic aneurysm: gene association in relation
      to metabolic risk factors and peripheral arterial disease coexistence.
AB  - An inadequate selenium level is supposed to be a risk factor for cardiovascular
      diseases. However little is known about variation of the genes encoding selenium
      containing proteins that would confirm the causality in these diseases. The aim
      of this study was to analyze the relationships between two functional variants of
      selenoprotein P gene (SEPP1 rs3877899G>A, rs7579G>A) and the occurrence of
      abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AIOD), as well
      as their metabolic risk factors. In AAA, the rs3877899A allele was associated
      with higher systolic blood (P < .003) and pulse pressure (P < .003) values
      (recessive model), and with coexistence of peripheral arterial disease (PAD;
      carriers: P = .033). The other SEPP1 variants were associated with BMI values and
      influenced the risk of aortic diseases, depending on body weight. The strongest
      associations in the case-control analysis was found between the presence of the
      rs3877899G-rs7579G haplotype and development of AAA in overweight and obese
      subjects (OR = 1.80, 95%CI = 1.16-2.79, P = .008). The higher BMI values were
      correlated with lower age of AAA patients and larger size of aneurysm. Our
      results suggests the potential role of the selenoprotein P in pathogenesis of
      AAA. Future studies should consider the role of the rs3877899G-rs7579G haplotype
      as a risk factor for aggressive-growing AAAs. 

PMID- 25395086
TI  - Effects of PTEN on the longevity of cultured human umbilical vein endothelial
      cells: the role of antioxidants.
AB  - Ageing is a major cause of illness, disease and mortality, mainly due to the
      shortening of telomeres, resulting in cells undergoing senescence and apoptosis.
      Increasing autophagy and the levels of antioxidants removes oxidants that cause
      DNA and telomere damage, thus reducing the rate at which telomeres shorten,
      resulting in a longer cellular lifespan. Phosphatase and tensin homolog (PTEN)
      has been shown to increase the lifespan of organisms by upregulating pathways
      involved in DNA damage repair, autophagy/antioxidants. The aim of this study was
      to investigate the effects of the overexpression of PTEN on the longevity of
      human cell cultures by examining the increase in antioxidant potential. Human
      umbilical vein endothelial cell (HUVEC) cultures were transfected with PTEN
      plasmids using lipofectamine. An assay was performed to quantify the protein
      levels of PTEN and the antioxidant potential of the cell cultures. The cell
      cultures were maintained until senescence occurred in order to determine
      longevity. The results of each assay were then compared and correlated with each
      other and with the longevity of the cells. The transfected cultures showed a
      significant increase in PTEN protein levels, total antioxidant potential and
      longevity (all P-values <0.001) compared with the non-transfected cell cultures.
      The correlation coefficient between cell longevity and PTEN levels was 0.8727;
      and the correlation coefficient between cell longevity and antioxidant potential
      was 0.6564. The successful transfection of PTEN led to an increase in PTEN
      levels, antioxidant potential and an increased cellular longevity. This study
      demonstrates that there is a potential for PTEN to be used to extend human
      longevity. This can lay the foundation for further studies to be carried out on
      humans involving PTEN and longevity.

PMID- 25395087
TI  - Fifty years of the ICSH: 1964 to 2014.

PMID- 25395088
TI  - Inhibition of acid-sensing ion channels by levo-tetrahydropalmatine in rat dorsal
      root ganglion neurons.
AB  - Levo-tetrahydropalmatine (l-THP), a main bioactive Chinese herbal constituent
      from the genera Stephania and Corydalis, has been in use in clinical practice for
      years in China as a traditional analgesic agent. However, the mechanism
      underlying the analgesic action of l-THP is poorly understood. This study shows
      that l-THP can exert an inhibitory effect on the functional activity of native
      acid-sensing ion channels (ASICs), which are believed to mediate pain caused by
      extracellular acidification. l-THP dose dependently decreased the amplitude of
      proton-gated currents mediated by ASICs in rat dorsal root ganglion (DRG)
      neurons. l-THP shifted the proton concentration-response curve downward, with a
      decrease of 40.93% +/- 8.45% in the maximum current response to protons, with no
      significant change in the pH0.5 value. Moreover, l-THP can alter the membrane
      excitability of rat DRG neurons to acid stimuli. It significantly decreased the
      number of action potentials and the amplitude of the depolarization induced by an
      extracellular pH drop. Finally, peripherally administered l-THP inhibited the
      nociceptive response to intraplantar injection of acetic acid in rats. These
      results indicate that l-THP can inhibit the functional activity of ASICs in
      dissociated primary sensory neurons and relieve acidosis-evoked pain in vivo,
      which for the first time provides a novel peripheral mechanism underlying the
      analgesic action of l-THP.

PMID- 25395089
TI  - Effective local control of vertebral metastases by simultaneous integrated boost
      radiotherapy: preliminary results.
AB  - BACKGROUND: The primary endpoint was to improve local tumour control of patients
      with metastatic spinal tumours by stereotactic body radiotherapy (SBRT) and dose
      escalation by simultaneous, integrated boost (PTV-boost). We used a whole
      vertebral body (PTV-elective) contouring approach. Secondary endpoints were
      severity of acute and chronic adverse effects and overall survival. METHODS: In
      all, 33 patients with metastases of the vertebral column were treated at Erlangen
      University Hospital. SBRT was given in 12 or 10 fractions. The metastatic lesion
      (PTV-boost) received 3.6 Gy (range 3.0-4.51 Gy) per fraction for a total of 42.0
      Gy (24.36-48.0 Gy) and the whole vertebra (PTV-elective) received 2.85 Gy (range
      1.8-3.6 Gy) per fraction for a total of 32.39 Gy (range 21.60-38.0 Gy). Patients
      were followed up every 3 months. RESULTS: Local control rate of all patients was
      93% at 12 and 24 months. The overall survival rate was 54% at 12 months, 38% at
      24 months and 18% at 36 months. No radiation myelopathy occurred. The most
      frequently observed adverse events in 3 cases was oesophagitis grade 2.
      CONCLUSION: SBRT with simultaneous, integrated boost was associated with
      excellent local control of 93% after 24 months. This result shows the possibility
      of delivering escalated doses to the target while still keeping the incidence of
      side effects low. This study forms the basis for a future randomised controlled
      trial comparing conventional radiotherapy (10 fractions of 3 Gy) with
      hypofractionated dose intensified SBRT (12 fractions of 3 Gy + integrated boost
      12 fractions of 4 Gy) for improvement of local tumour control and pain.

PMID- 25395090
TI  - [Obituary Prof. Dr. Christian Herfarth].

PMID- 25395092
TI  - Is local resection adequate for T1 stage ampullary cancer?
AB  - BACKGROUND: Concerns for morbidity after a pancreaticoduodenectomy (PD) has led
      to practitioners adopting endoscopic resection or ampullectomy in the treatment
      of T1 ampullary cancer (AC). It was hypothesized that survival for patients
      undergoing local resection of AC was inferior to those undergoing a PD. METHODS:
      All the data of patients with AC reported in the Surveillance, Epidemiology and
      End Results (SEER) database between 2004 and 2010 were collected. Five-year
      survival rates according to nodal disease and histological type were compared.
      RESULTS: There were 1916 cases of AC; 421 (22%) had T1 disease. Among those with
      T1 disease, 217 (51%) received endoscopic surveillance, 21 (5%) underwent local
      resection/ampullectomy, 20 (5%) underwent ampullectomy with regional
      lymphadenectomy and 163 (39%) underwent PD. For patients with complete nodal
      staging (PD, n = 163), 35 (22%) had metastatic disease in the nodes. Grade was
      significantly associated with node positivity (P = 0.007). In multivariate
      models, survival was improved with either an ampullectomy with regional
      lymphadenectomy [hazard ratio (HR) 0.19; 95% confidence interval (CI) 0.05-0.61,
      P < 0.005] or a PD (HR 0.23; 95% CI 0.15-0.36, P < 0.001). CONCLUSION: Patients
      with T1 AC have a high risk for nodal metastases especially if they are higher
      grade lesions. Nodal clearance with a lymphadenectomy or a PD is essential for
      long-term survival in these patients.

PMID- 25395093
TI  - It's About Time for Autism Reform Legislation in Utah.
AB  - On 3 April 2014, Governor Gary Herbert signed into law a health insurance reform
      bill that requires private insurers to cover autism therapy. Specifically, SB57
      requires state-regulated health plans to cover applied behavior analysis (ABA)
      therapy. While early diagnosis and intervention can reduce the long-term cost of
      autism, families are finding themselves bankrupt in order to pay for ABA therapy.
      Currently, 37 states, and the District of Columbia have enacted insurance reform
      laws. Ensuring that children with autism receive proper therapy is a serious
      public health issue. Utah was right to pass reform legislation because it
      properly benefits and safeguards the interests of affected children in promoting
      their well-being and participation in society. 

PMID- 25395095
TI  - Salivary biomarkers indicate obstructive sleep apnea patients with cardiovascular
      diseases.
AB  - Although obstructive sleep apnea (OSA) patients are at high risk of developing
      cardiovascular disease (CVD), only a small proportion is currently diagnosed. To
      explore and identify the differentially expressed proteins/peptides of OSA
      patients with CVDs, a mass spectrometry-based salivary analysis was performed. In
      our study, eleven peaks were observed differentially expressed in saliva from the
      non-CVD and CVD groups. Five masses mass peaks (1594.1, 1673.7, 1196.6, 1290.5,
      and 1447.0 Da) showed an upregulated trend in the CVD group, whereas six mass
      peaks (3038.6, 2164.3, 2301.4, 3195.0, 2628.4, and 1721.9 Da) were downregulated
      in the CVD group. In addition, the alpha-2-HS-glycoprotein (AHSG) levels in
      saliva were verified to be decreased in CVD group compared to non-CVD group.
      Analysis of the salivary peptidome provides a promising approach to screening for
      novel biomarkers before further identification, and may contribute to early
      diagnosis of CVD patients with OSA.

PMID- 25395097
TI  - Overexpression of activated leukocute cell adhesion molecule in gastric cancer is
      associated with advanced stages and poor prognosis and miR-9 deregulation.
AB  - Activated leukocyte cell adhesion molecule (ALCAM) has been identified as a novel
      potential molecular marker of human tumors. The present study aimed to assess
      ALCAM as a prognostic marker for gastric cancer (GC), and to explore the mRNA
      deregulation underlying the abnormal expression of ALCAM. The mRNA and protein
      expression of ALCAM in GC and adjacent non-tumor tissues from 66 patients with GC
      were analyzed. The association between miR-9 and ALCAM mRNA expression was
      determined by quantitative polymerase chain reaction. Serum soluble ALCAM
      (sALCAM) was analyzed by ELISA in 72 patients with GC, 82 patients with gastric
      precancerous lesions and 73 controls. ALCAM and sALCAM levels were associated
      with certain clinicopathological variables, including overall survival. Compared
      with the non-tumor tissues, the expression of ALCAM mRNA in the GC tissues was
      significantly upregulated (P=0.013). The expression of miR-9 was reduced and
      inversely correlated with ALCAM mRNA levels in GC tissues and cell lines. The
      ALCAM mRNA level was reduced following ectopic overexpression of miR-9 in SGC
      7901 human gastric cancer cells. The rates of membranous and cytoplasmic
      expression of ALCAM in GC tissues were 59.1 and 48.48%, respectively, and the
      serum sALCAM levels were significantly elevated in patients with GC. Elevated
      ALCAM mRNA, membranous ALCAM expression in GC tissues and high sALCAM levels are
      associated with advanced tumor stage, lymphatic invasion and shorter overall
      survival duration. The results of the current study indicated that membranous
      ALCAM expression and high serum sALCAM levels are independent prognostic markers
      of poor survival for patients with GC, and that the overexpression of ALCAM may
      be due to the downregulation of miR-9.

PMID- 25395094
TI  - Multidisciplinary assessment and treatment of self-injurious behavior in autism
      spectrum disorder and intellectual disability: integration of psychological and
      biological theory and approach.
AB  - The objective of this review is to consider the psychological (largely
      behavioral) and biological [neurochemical, medical (including genetic), and
      pharmacological] theories and approaches that contribute to current thinking
      about the etiology and treatment of self-injurious behavior (SIB) in individuals
      with autism spectrum disorder and/or intellectual disability. Algorithms for the
      assessment and treatment of SIB in this context, respectively, from a
      multidisciplinary, integrative perspective are proposed and challenges and
      opportunities that exist in clinical and research settings are discussed. 

PMID- 25395098
TI  - Reactivity of a stable phosphinonitrene towards small molecules.
AB  - The room-temperature stable phosphinonitrene 1 undergoes a thermal rearrangement
      into heterocycle 2 through a process involving a nitrene insertion into a CH
      bond. In the presence of acetonitrile, a nitrene-acetonitrile adduct has been
      isolated; then it first rearranges into a ketenimine and subsequently into a rare
      example of diazaphosphete. Compound 1 also splits water, carbon dioxide, carbon
      disulfide, and elemental sulfur, although it reacts with white phosphorus,
      leading to a P5 N cluster formally resulting from the insertion of the PN moiety
      into a P-P edge of the P4 tetrahedron.

PMID- 25395096
TI  - Short-term airborne particulate matter exposure alters the epigenetic landscape
      of human genes associated with the mitogen-activated protein kinase network: a
      cross-sectional study.
AB  - BACKGROUND: Exposure to air particulate matter is known to elevate blood
      biomarkers of inflammation and to increase cardiopulmonary morbidity and
      mortality. Major components of airborne particulate matter typically include
      black carbon from traffic and sulfates from coal-burning power plants. DNA
      methylation is thought to be sensitive to these environmental toxins and possibly
      mediate environmental effects on clinical outcomes via regulation of gene
      networks. The underlying mechanisms may include epigenetic modulation of major
      inflammatory pathways, yet the details remain unclear. METHODS: We sought to
      elucidate how short-term exposure to air pollution components, singly and/or in
      combination, alter blood DNA methylation in certain inflammation-associated gene
      networks, MAPK and NF-kappaB, which may transmit the environmental signal(s) and
      influence the inflammatory pathway in vivo. To this end, we utilized a custom
      integrated workflow-molecular processing, pollution surveillance, biostatical
      analysis, and bioinformatic visualization-to map novel human (epi)gene pathway
      environment interactions. RESULTS: Specifically, out of 84 MAPK pathway genes
      considered, we identified 11 whose DNA methylation status was highly associated
      with black carbon exposure, after adjusting for potential confounders-age,
      sulfate exposure, smoking, blood cell composition, and blood pressure. Moreover,
      after adjusting for these confounders, multi-pollutant analysis of synergistic
      DNA methylations significantly associated with sulfate and BC exposures yielded
      14 MAPK genes. No associations were found with the NF-kappaB pathway. CONCLUSION:
      Exposure to short-term air pollution components thus resulted in quantifiable
      epigenetic changes in the promoter areas of MAPK pathway genes. Bioinformatic
      mapping of single- vs. multi-exposure-associated epigenetic changes suggests that
      these alterations might affect biological pathways in nuanced ways that are not
      simply additive or fully predictable via individual-level exposure assessments.

PMID- 25395099
TI  - Reply: A single session of cerebellar theta burst stimulation does not alter
      writing performance in writer's cramp.

PMID- 25395100
TI  - A single session of cerebellar theta burst stimulation does not alter writing
      performance in writer's cramp.

PMID- 25395101
TI  - Management of Peyronie's disease after collagenase (Xiaflex:(r)).
AB  - Although the prevalence of Peyronie's disease (PD) is reported to be 3-9% in men,
      the true prevalence is likely higher due to under-reporting. Many treatment
      modalities have been described for PD with varying degrees of success. In this
      article, we review and summarize the current literature pertaining to all
      pharmacotherapies (oral, intralesional, iontophoresis, and topical) and minimally
      invasive treatments available for PD (vacuum, traction device, shock wave
      therapy, and radiation treatment). Additionally, we discuss emerging therapies
      for PD that are still in pre-clinical development, including stem cell therapy. 

PMID- 25395102
TI  - Pharmacological modulation of reactive oxygen species in cancer treatment.
AB  - Aerobic metabolism of mammalian cells leads to the generation of reactive oxygen
      species (ROS). To cope with this toxicity, evolution provided cells with
      effective antioxidant systems like glutathione. Current anticancer therapies
      focus on the cancer dependence on oncogenes and non-oncogenes. Tumors trigger
      mechanisms to circumvent the oncogenic stress and to escape cell death. In this
      context we have studied 2-phenylethinesulfoxamine (PES), which disables the cell
      protective mechanisms to confront the proteotoxicity of damaged and unfolded
      proteins. Proteotoxic stress is increased in tumor cells, thus providing an
      explanation for the anticancer selectivity of PES. In addition, we have found
      that PES induces a severe oxidative stress and the activation of p53. The
      reduction of the cell content in glutathione by means of L-buthionine-sulfoximine
      (BSO) synergizes with PES. In conclusion, we have found that ROS constitutes a
      central element in a series of positive feed-back loops in the cell. ROS, p53,
      proteotoxicity, autophagy and mitochondrial dynamics are interconnected with the
      mechanisms leading to cell death, either apoptotic or necrotic. This network of
      interactions provides multiple targets for drug discovery and development in
      cancer. 

PMID- 25395103
TI  - Targeted Drug Delivery Systems for Lung Macrophages.
AB  - Lung macrophages present an effective role in innate and immune response through
      specific and non-specific mechanisms, namely phagocytosis, antigen processing and
      presentation through major histocompatibility complex, activation of T cells and
      inflammatory cytokines release. Despite their protective role against injury in
      normal condition, they can cause several lung conditions, since they can mediate
      several processes, through recruitment of other inflammatory cells for alveolar
      space, release of proinflammatory cytokines or stimulation of collagen
      deposition. Lung macrophages constitute a good therapeutic target. With the
      development of nanotechnology, new carriers have been designed to target drugs
      towards these cells. One of the commonly used approaches is the attachment of
      ligands with affinity to receptors presented at lung macrophage surface, to the
      nanocarriers. This review will focus on the importance of lung macrophages in
      host-defense, their influence on different pulmonary diseases and different
      strategies for alveolar macrophage targeting. 

PMID- 25395104
TI  - Polymeric Aggregates in Ionic Liquids: The Green Future of the Delivery Systems.
AB  - The self-assembly of a series of triblock co polymers Pluronics (P85, P105 and
      L121) has been investigated in some ionic liquids (BMIMBF4, BMIMPF6 and BMIMTf2N)
      by using Near-Infrared spectroscopy. The formation of supramolecular s tructures
      has been confirmed by optical microscopy. The solvation degree and the
      aggregation behaviour of P85, P105 and L121 depend on the interactions between
      the imidazolium ring of the ionic liquid and the hydrophilic moiety of the
      copolymer. Fluorescent vesicles can be observed after the incorporation of Nile
      Red into the polymeric bilayer of L121 or by linking fluorescein isothiocyanate
      to the copolymer structure. 

PMID- 25395105
TI  - Trastuzumab-induced cardiotoxicity: is it a personalized risk?
AB  - Optimal identification of the risk of developing cardiotoxicity upon trastuzumab
      (TZM) treatment appears necessary as this risk may impair treatment compliance
      and compromise long-term recovery. To better understand and predict cardiac
      toxicity, the molecular mechanisms underlying this phenomenon need to be known.
      HER2 is present at the cell surface of cardiomyocytes. Neuregulin is produced by
      cardiac endothelial cells and binds to HER4, thus leading to dimerization with
      HER2 and subsequent cell signaling necessary for normal cardiac function.
      Decreasing HER2 activity has a major impact on cardiomyocyte function. However,
      the precise molecular mechanisms responsible for TZM-induced cardiac dysfunction
      are still unclear. This mini-review aims to summarize genetic, pharmacological
      and medical data helping to identify mechanisms that could explain
      cardiotoxicity. Of potential interest, these mechanisms highlight the importance
      of HER2 genetic polymorphism (Val655Ile) in the identification of patients at
      risk of developing TZM-induced cardiac effects.

PMID- 25395106
TI  - The effect of adherence to guidelines for initial antiretroviral therapy on 1
      year outcomes: a French cohort study.
AB  - BACKGROUND: Guidelines for antiretroviral treatment (cART) are published
      regularly, but there is little information regarding the effect of adherence to
      guidelines on patient outcomes. We assessed the effect of following the "when-to
      start" and "what-to-start" guidelines, on treatment modifications, and on
      immunological and virological outcome at 12 months in a cohort of HIV-1 infected
      patients initiating cART from 2000 to 2010. METHODS: Consecutive HIV-1 infected
      patients, antiretroviral naive, initiating cART from 2000 to 2010 at a University
      Hospital were enrolled. HIV-2 infection, cART for prevention of mother-to-child
      transmission or during primary HIV-infection and unlicensed drugs were excluded.
      The respect or not of the "when-to-start" and "what-to-start" guidelines was
      based on French guidelines published from 2000 to 2010. Factors associated with
      cART modifications at 12 months and factors associated with an HIV viral load of
      <50 copies/mL at 12 months were assessed by univariate and multivariate logistic
      regression modeling. Variations in CD4 counts from baseline were assessed by
      univariate and multivariate linear regression. RESULTS: Of 1365 patients starting
      cART, 151 were treated outside "when-to-start" guidelines and 150 were treated
      outside "what-to-start" guidelines. Not using "when-to-start" guidelines was
      mainly related to early initiation in young men having sex with men, and was not
      associated with a significantly different outcome at 12 months. Treatments that
      did not follow "what-to-start" guidelines were not observed in any specific
      population and were associated with more treatment modifications and a poorer
      virological outcome at 12 months. CONCLUSIONS: Adherence to "what-to-start"
      guidelines is associated with a better outcome at 12 months in HIV-infected
      patients initiating antiretroviral therapy. Efforts should be made to promote
      adherence to these guidelines.

PMID- 25395107
TI  - Effects of germination time on seed morph ratio in a seed-dimorphic species and
      possible ecological significance.
AB  - BACKGROUND AND AIMS: Diaspores of heteromorphic species may germinate at
      different times due to distinct dormancy-breaking and germination requirements,
      and this difference can influence life history traits. The primary aim of this
      study was to determine the effect of germination time of the two seed morphs of
      Suaeda corniculata subsp. mongolica on life history traits of the offspring.
      METHODS: Germinated brown and black seeds were sown on the 20th of each month
      from April to September in a simulated but near-natural habitat of the species.
      Phenological and vegetative traits of the maternal plants, and number, size and
      germination percentage of the offspring were determined. KEY RESULTS: Germinated
      seeds sown late in the year produced smaller plants that had a higher proportion
      of non-dormant brown than dormant black seeds, and these brown seeds were larger
      than those produced by germinated seeds sown early in the year. The length of the
      seedling stage for brown seeds was shorter than that for black seeds, and the
      root/shoot ratio and reproductive allocation of plants from brown seeds were more
      variable than they were for plants from black seeds. Late-germinating brown seeds
      produced larger plants than late-germinating black seeds. CONCLUSIONS: Altering
      the proportion of the two seed types in response to germination timing can help
      alleviate the adverse effects of delayed germination. The flexible strategy of a
      species, such as S. corniculata, that produces different proportions of dimorphic
      seeds in response to variation in germination timing may favour the maintenance
      and regeneration of the population in its unpredictable environment.

PMID- 25395108
TI  - Process development for the decoloration of Panax notoginseng extracts: a design
      space approach.
AB  - A systematic, yet simple method for the decoloration of Panax notoginseng
      extracts has been developed by static adsorption tests and response surface
      methodology. Through static adsorption experiment screening, acidic alumina was
      selected because of its high decoloration ratio and saponin recovery ratios.
      Using response surface methodology, the correlation between the process
      parameters (i.e., sample volume and flow rate) and decoloration performance was
      modeled. A design space of the decoloration process was subsequently established
      through the proposed models. The verification experimental values were in good
      agreement with the predicted values. The design space was proven reliable,
      because all the verification experimental results attained the criteria for
      design space development. Moreover, most of the saponins adsorbed by the acidic
      alumina could be recovered through dynamic desorption using water and ethanol.
      The method developed in the current study is highly efficient, flexible, and easy
      to control, thus providing a promising approach for the decoloration of Panax
      notoginseng extracts with consistent decoloration performance. 

PMID- 25395109
TI  - Refractive error, binocular vision and accommodation of children with Down
      syndrome.
AB  - BACKGROUND: In this review of the visual development of children with Down
      syndrome we were specifically interested in how refractive error, binocular
      alignment and accommodation are different in Down syndrome from the general
      population. The differences and their aetiology will help practitioners make
      informed decisions about the visual assessment and management of these children.
      METHODS: Articles found using searches through Scopus, Medline and Google Scholar
      were evaluated by examining sample sizes, appropriate use of controls, methods of
      measurement and statistical significance of findings. Where the strength of
      evidence in an article might be weak, this is reported in the review. CONCLUSION:
      The development of the visual and oculomotor systems is substantially different
      in Down syndrome compared with the general population. Assessment and optometric
      management of this special population need to be directed accordingly.

PMID- 25395110
TI  - Chronic low back pain: a supplement to Neuromodulation.

PMID- 25395111
TI  - Epidemiology of low back pain in adults.
AB  - OBJECTIVE: Low back pain affects many individuals. It has profound effects on
      well-being and is often the cause of significant physical and psychological
      health impairments. Low back pain also affects work performance and social
      responsibilities, such as family life, and is increasingly a major factor in
      escalating health-care costs. A global review of the prevalence of low back pain
      in the adult general population has shown its point prevalence to be
      approximately 12%, with a one-month prevalence of 23%, a one-year prevalence of
      38%, and a lifetime prevalence of approximately 40%. Furthermore, as the
      population ages over the coming decades, the number of individuals with low back
      pain is likely to increase substantially. This comprehensive review is undertaken
      to assess the increasing prevalence of low back pain and the influence of
      comorbid factors, along with escalating costs. MATERIALS AND METHODS: A narrative
      review with literature assessment. RESULTS: In the USA, low back pain and related
      costs are escalating. Based on the available literature, it appears that the
      prevalence of low back pain continues to increase, along with numerous modalities
      and their application in managing low back pain. Comorbid factors with
      psychological disorders and multiple medical problems, including obesity,
      smoking, lack of exercise, increasing age, and lifestyle factors, are considered
      as risk factors for low back pain. CONCLUSION: Although it has been alleged that
      low back pain resolves in approximately 80% to 90% of patients in about six
      weeks, irrespective of the administration or type of treatment, with only 5% to
      10% of patients developing persistent back pain, this concept has been frequently
      questioned as the condition tends to relapse and most patients experience
      multiple episodes years after the initial attack.

PMID- 25395112
TI  - The differential diagnosis of low back pain: a primer on the evolving paradigm.
AB  - OBJECTIVES: The issue of low back pain (LBP) is as common as it is perplexing.
      LBP is thought to be a chronic issue in approximately 10% of the U.S. population.
      This condition has wide-reaching social and economical reverberations. Despite
      the availability of modern diagnostic tools, the cause of the pain generator is
      often unidentifiable. The authors were asked to create an overview of the
      etiology of LBP for physicians who implant neurostimulation devices for the
      treatment of chronic pain patients. Some prevalence data, based on the current
      available literature, have been provided for the more common structural
      conditions causing LBP. However, a comprehensive review of prevalence of various
      conditions and their respective manifestations as LBP is beyond the scope of this
      article. MATERIALS AND METHODS: A review was performed of frequently cited
      articles with search terms for "low back pain" using PubMed, Medline, and Google
      Scholar. The authors also reviewed other literature from commonly utilized
      sources in the field of interventional pain medicine such as the journals of
      Neuromodulation, Pain Medicine, Spine, and Neurosurgery in the publication date
      range of 1975 to the present. Moreover, recent edition textbooks of other
      specialties such as obstetrics and gynecology, neurology, internal medicine, and
      surgery were referenced to develop a comprehensive list of the differential
      diagnoses. In order to capture the broad scope of information presented in this
      article, the criteria used to choose the references included published peer
      reviewed articles that provided information on LBP as a symptom of a case report
      to common presentations of various conditions as described in a number of
      current, and commonly used, textbooks in their specialty. RESULTS: The article
      serves as a reference for commonly cited causes of LBP as well as less common
      conditions presenting with LBP as a possible symptom, which may occur as a
      solitary pain generator or in combination with other etiologies. The information
      is structured in such a fashion to allow a comprehensive overview for every
      reader, including the most experienced implanting physicians. The article is
      designed to kindle critical thinking regarding the massive scope involved in the
      assessment of a patient with a complaint of LBP. The results of the comprehensive
      research to produce this article clearly indicate the broad scope of this list of
      differential diagnoses. The reader should be aware that the lists are by no means
      all-inclusive. Perhaps additional efforts will be necessary to build on the
      available information in this article in the future. Furthermore, although some
      prevalence data for LBP, as it is related to structural spine, is readily
      available based on the excellent work of our colleagues and presented throughout
      this paper, for other disease processes, the prevalence data are scarce to
      nonexistent. This underscores the need for further research to better understand
      this elusive condition. The size and breadth of the topic at hand in this article
      would arguably deserve its own comprehensive textbook. The complexity and
      discussion points of each identified pain generator could be given a chapter or
      section to reflect complex learning deserved by each topic. With these
      limitations, the authors recommend the reader to evaluate this article in the
      context of a broader topic of LBP and neurostimulation. CONCLUSIONS: LBP is an
      extremely common condition associated, as a symptom, with various disease
      processes, regardless of their relationship with the lumbar spine or its
      innervation. This article underscores the broad nature of LBP as a symptom of
      many diagnoses. The primary conclusion reached by the authors is the most
      important recommendation by all mentors in medicine, which is to obtain a
      comprehensive history and perform a complete physical examination on each
      patient. Despite the fact that there is an emerging school of thought questioning
      the validity of the physical examination, this tool continues to be the current
      standard of care and used by a majority of clinicians around the world. The
      physician must analyze the information obtained from his/her history, physical
      examination, and diagnostic tools with the recognition of the broad nature of the
      differential diagnoses of LBP in order to be able to best treat the patient.

PMID- 25395113
TI  - Medical management of chronic low back pain: efficacy and outcomes.
AB  - OBJECTIVES:   Chronic low back pain (CLBP) is common and contributes to
      significant disability and healthcare costs. The mechanism and etiology of CLBP
      are frequently unclear, and treatment choices vary. MATERIALS AND METHODS:   The
      scientific literature, including expert-generated treatment guidelines, was
      reviewed and evaluated for data regarding CLBP prevalence and predictors and for
      evidence of outcomes from pharmacologic and nonpharmacologic therapies. RESULTS: 
      Evidence is inconclusive as to superior treatments for CLBP. Even therapies with
      literature support, including cognitive-behavioral therapy, nonsteroidal anti
      inflammatory drugs, and opioids administered short term, do not work for every
      patient, and combination therapies are frequently beneficial. Early intervention
      with acute pain may stop the progression to chronicity in predisposed patients;
      however, much acute back pain resolves spontaneously. Predictors of chronicity
      include continuing poor function, unwillingness to remain active, psychiatric
      comorbidities, general poor health, and maladaptive coping strategies. Indefinite
      diagnoses and genetic vulnerabilities are likely factors in variable patient
      outcomes. CONCLUSIONS:   Personalized treatment plans should be informed by
      response to therapies previously tried, the severity and persistence of symptoms,
      and the availability of specialist expertise.

PMID- 25395114
TI  - Noninvasive and alternative management of chronic low back pain (efficacy and
      outcomes).
AB  - OBJECTIVES: The goal of this article is to provide a thorough literature review
      of available noninvasive and alternative treatment options for chronic low back
      pain. In particular, the efficacy of each therapy is evaluated and pertinent
      outcomes are described. MATERIALS AND METHODS: A comprehensive search for
      available literature was done through PubMed and Cochrane data base for topics
      discussed in this paper. RESULTS: Relevant current and past references were
      reviewed and presented to reflect the efficacy of each therapy and related
      outcomes. CONCLUSIONS: There are a wide variety of noninvasive and alternative
      therapies for the treatment of chronic low back pain. Those with the strongest
      evidence in the literature for good efficacy and outcomes include exercise
      therapy with supervised physical therapy, multidisciplinary biopsychosocial
      rehabilitation, and acupuncture. Therapies with fair evidence or moderately
      supported by literature include yoga, back schools, thermal modalities,
      acupressure, and cognitive-behavioral therapy. Those therapies with poor evidence
      or little to no literature support include manipulation, transcutaneous
      electrical nerve stimulation, low-level laser therapy, reflexology, biofeedback,
      progressive relaxation, hypnosis, and aromatherapy. Providers delivering care for
      patients with chronic low back pain must carefully evaluate these available
      treatment options related to their efficacy or lack thereof as well as relevant
      outcomes.

PMID- 25395115
TI  - Interventional therapies for chronic low back pain.
AB  - OBJECTIVE: Low back pain (LBP) is a highly prevalent condition and one of the
      leading causes of lost productivity and health-care costs. The objective of this
      review is to discuss the role of interventional pain procedures and evidence of
      their effectiveness in treatment of chronic LBP. METHODS: This is a narrative
      review examining published studies on interventional procedures for LBP. The
      rationales, indications, technique, evidence, and complications for the
      interventional procedures are discussed. RESULTS: Interventional pain procedures
      are used extensively in diagnosis and treatment of chronic pain. LBP is
      multifactorial, and while significant progress has been made in understanding its
      pathophysiology, this has not resulted in a proportional improvement of
      functional outcomes. For certain procedures, such as spinal cord stimulation,
      medical branch blocks and radiofrequency ablations, and epidural steroid
      injections for radiculopathy, safety, efficacy, and cost-effectiveness in
      treating LBP have been well studied. For others, such as interventions for
      discogenic pain, treatment successes have been modest at best. CONCLUSIONS:
      Implementation of interventional pain procedures in the treatment framework of
      LBP has resulted in improvement of pain intensity in at least the short and
      medium terms, but equivocal results have been observed in functional improvement.

PMID- 25395116
TI  - Anatomic surgical management of chronic low back pain.
AB  - OBJECTIVE: To review spine surgery management strategies for patients with
      chronic low back pain (CLBP) that has failed to respond to all nonsurgical
      treatment options. MATERIALS AND METHODS: Literature review was conducted for
      spine surgery in the treatment of CLBP without compressive anatomical disease.
      The main diagnosis identified was degenerated disc disease, and surgical options
      targeted for the treatment of CLBP were reviewed. RESULTS: The history of current
      spine intervention for CLBP was reviewed, including various surgical options.
      Surgical treatment options for patients with CLBP include lumbar fusion, lumbar
      disc arthroplasty, and dynamic stabilization. Lumbar fusion remains the most
      frequent spine surgery performed for CLBP, but questions still exist regarding
      its efficacy in comparison with conservative care or interventional pain
      management. Lumbar disc arthroplasty and dynamic stabilization can both be
      considered only for select patients with CLBP, and their uses are currently
      limited. CONCLUSION: Despite the number of spine surgeries that have been
      performed for CLBP, the surgical outcome still remains questionable. Until a
      precise identification of the cause of CLBP in any given patient can be precisely
      determined, surgical solutions will continue to be less than optimal.

PMID- 25395117
TI  - Neurostimulation for the treatment of axial back pain: a review of mechanisms,
      techniques, outcomes, and future advances.
AB  - INTRODUCTION: The use of spinal cord stimulation (SCS) is well established in the
      treatment of neuropathic pain. This procedure has been approved in the United
      States for neuropathic pain of the trunk and limbs from various conditions.
      International use is variable based on governmental policy. Most studies showing
      efficacy have focused on pain primarily in the limbs for such conditions as
      complex regional pain syndrome (CRPS), sciatica, radiculitis, ischemic limb pain,
      and peripheral neuropathy. Data on success in neuropathic pain of the trunk and
      particularly of the axial back are limited. New understanding about the targets
      of neuromodulation and their treatment with novel neurostimulation approaches has
      led to a new dawn of enthusiasm for spinal cord stimulation for axial low back
      pain. METHODS: The authors review mechanisms, current and future targets,
      techniques, and their outcomes for treating axial back pain with
      neurostimulation. The paper discusses many newer methods and targets that may
      substantially improve results for the treatment of this patient group. The
      continuing evolution of technology and new data may well change these
      recommendations over time and regular updates of this manuscript will be critical
      moving forward. CONCLUSIONS: Improved technology and a better understanding of
      the goals of stimulation have led to a new ability to stimulate the axial low
      back and increase the effectiveness of these therapies to reduce pain. New paddle
      lead constructs, percutaneous paddle lead introduction, and other new
      technologies have led to an increased number of potential candidates for spinal
      cord stimulation. Optimizing the application of neurostimulation for chronic
      axial back pain will depend upon answering questions relating to patient
      selection, implantation technique, and stimulation parameters.

PMID- 25395118
TI  - A review of economic factors related to the delivery of health care for chronic
      low back pain.
AB  - INTRODUCTION AND METHODS: We describe tools used to evaluate the economic impact
      of health care interventions, discuss the economic burden of chronic low back
      pain, and review evidence on the cost-effectiveness of treating failed back
      surgery syndrome with spinal cord stimulation, intrathecal drug delivery,
      acupuncture, epidural injections, disc prosthesis, lumbar fusion, and noninvasive
      therapies. We also mention the lack of cost studies for emerging therapies, such
      as vibrotherapy and peripheral nerve field stimulation. Topics include types of
      cost studies; the economic perspectives taken by such studies; direct and
      indirect costs; measures of success; definitions of cost-effectiveness,
      incremental cost-effectiveness, incremental cost-utility ratios, and quality
      adjusted life years; the concept of maximum willingness to pay; and the use of
      cost-effectiveness models. CONCLUSION: The fact that chronic low back pain arises
      from a variety of causes makes choosing appropriate treatment difficult.
      Determining the cost-effectiveness of various treatments for chronic low back
      pain depends on well-designed and well-executed randomized controlled trials with
      parallel economic evaluations. Researchers can use economic models to extrapolate
      costs and outcomes over the long term.

PMID- 25395119
TI  - Nanoscopic X-ray fluorescence imaging of meteoritic particles and diamond
      inclusions.
AB  - The new ESRF ID16B-NA Nanoanalysis beamline has been applied for the first time
      for XRF imaging with a resolution level down to a few tens of nanometers on rare
      geological materials: meteoritic fragments from achondrite NWA 6693 and diamond
      inclusions. The instrument proved to be an extremely valuable tool for mapping
      samples containing submicrometer heterogeneities. It was discovered that the
      track of bubblelike inclusions in NWA 6693 consists mainly of Cr-rich phases.
      Some inclusions containing Ni and Ca were also detected. In diamond SL05,
      originating from the Juina region in Brazil, multiple inclusions were analyzed
      with dimensions smaller than 1 MUm. Raman spectrometry measurements indicated the
      presence of a ringwoodite inclusion in this diamond; the detection of several
      iron-rich inclusions justifies further investigation of this material. 

PMID- 25395120
TI  - Non-anaplastic peripheral T-cell lymphoma in children and adolescents--a
      retrospective analysis of the NHL-BFM study group.
AB  - Mature (peripheral) T-cell lymphoma (PTCL) other than anaplastic large cell
      lymphoma is a heterogeneous group of diseases and exceedingly rare in children
      and adolescents. Survival rates range between 46% and 85%. This study reports the
      disease characteristics, treatment and outcome of all patients with the diagnosis
      of mature TCL registered in the Berlin-Frankfurt-Munster non-Hodgkin lymphoma
      database between 1986 and 2012. All diagnoses were centrally reviewed and revised
      by clinico-pathological correlation according to the criteria of the current
      World Health Organization classification. Of the 69 patients originally
      registered as having PTCL, the diagnosis was confirmed in 38 of them. Most
      patients were treated with an anaplastic large cell lymphoma (ALCL)-like therapy
      regimen. Patients with PTCL-not otherwise specified comprised the largest group
      and showed a 5-year event-free survival rate of 61 +/- 11%. Patients suffering
      from Natural Killer/T-cell- and hepatosplenic TCL had the poorest outcome. Our
      results suggest that the outcomes of children with mature TCL other than ALCL
      depend on the subtype and are worse than in all other paediatric lymphomas. The
      clinical experience presented in this largest study on paediatric mature TCL may
      serve as basis for future collaborative international prospective clinical
      trials. 

PMID- 25395121
TI  - A follow-up study of the chronic kidney disease patients treated with Brazil nut:
      focus on inflammation and oxidative stress.
AB  - Brazil nut is the richest known food source of selenium. The supplementation with
      Brazil nut during 3 months was effective in reducing oxidative stress and
      inflammation in hemodialysis (HD) patients. However, there are no available data
      on the antioxidant effect after that supplementation. The objective of this work
      was to determine if the beneficial effects of one Brazil nut supplementation per
      day during 3 months for the HD patients could be sustained after 12 months.
      Twenty-nine HD patients (58.6 % men, 51.0 +/- 3.3 years) from RenalCor Clinic,
      Rio de Janeiro, Brazil, were followed up 12 months after the supplementation
      study had finished. The plasma levels of antioxidant substances as selenium,
      glutathione peroxidase (GPx), 8-isoprostane, 8-hydroxy-2-deoxyguanosine (8-OHdG)
      and cytokines (tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6))
      were determined before, after 3 months of supplementation and after 12 months.
      After 3-months supplementation, cytokines, 8-OHdG and 8-isoprostane plasma levels
      have decreased and the activity of GPx and selenium plasma levels have increased
      significantly. Additionally, after 12 months, the values of 8-isoprostane, 8-OHdG
      and cytokines increased and the activity of GPx and selenium plasma levels
      decreased significantly. The levels of oxidative stress and inflammation
      biomarkers after 12 months increased compared to the basal levels. Consequently,
      it is necessary to motivate patients to adopt different dietary intake patterns. 

PMID- 25395122
TI  - Effects of prenatal and postnatal exposure of Wi-Fi on development of teeth and
      changes in teeth element concentration in rats. [corrected].
AB  - The present study determined the effects of prenatal and postnatal exposure to Wi
      Fi (2.45 GHz)-induced electromagnetic radiation (EMR) on tooth and surrounding
      tissue development as well as the element levels in growing rats. Twenty-four
      rats and their offspring were equally divided into two separate groups identified
      as experiment and control. The experiment group was exposed to 2.45 GHz EMR for 2
      h/day during the periods of pregnancy (21 days) and lactation (21 days). The
      offspring of these dams were also exposed to EMR up to decapitation. The control
      group was exposed to cage stress for 2 h per day using the same protocol
      established for the experimental group. On the 7th, 14th, and 21st days after
      birth, 8 male offspring rats from each of the two groups were decapitated, and
      the jaws were taken for histological and immunohistochemical examination. Caspase
      3 (1/50 dilution) was used in the immunohistochemical examination for apoptotic
      activity. On the last day of the experiment, the rats' incisors were also
      collected. In samples that were histologically and immunohistochemically
      examined, there was an increase in apoptosis and caspase-3 in both the control
      and the Wi-Fi groups during the development of the teeth. However, no significant
      difference was observed between the two groups in terms of development and
      apoptotic activity. Results from the elemental analysis showed that iron and
      strontium concentrations were increased in the Wi-Fi group, whereas boron,
      copper, and zinc concentrations were decreased. There were no statistically
      significant differences in calcium, cadmium, potassium, magnesium, sodium, or
      phosphorus values between the groups. Histological and immunohistochemical
      examinations between the experimental and control groups showed that exposure to
      2.45 GHz EMR for 2 h per day does not interfere with the development of teeth and
      surrounding tissues. However, there were alterations in the elemental composition
      of the teeth, especially affecting such oxidative stress-related elements as
      copper, zinc, and iron, suggesting that short-term exposure to Wi-Fi-induced EMR
      may cause an imbalance in the oxidative stress condition in the teeth of growing
      rats. 

PMID- 25395123
TI  - 'Extreme mass spectrometry': the role of mass spectrometry in the study of the
      Antarctic environment.
AB  - A focus on the studies of the Antarctic environment that have been performed by
      mass spectrometry is presented herein; our aim is to give evidence of the
      essential role of this instrumental technique in the framework of the scientific
      research in Antarctica, with a comprehensive review on the main literature of the
      last two decades. Due to the wideness of the topic, the present review is limited
      to the determination of organic pollutants, natural molecules and biomarkers in
      Antarctica, thus excluding elemental analysis and studies on inorganic species.
      The work has been divided into five sections, on the basis of the considered
      environmental compartment: air; ice and snow; seawater, pack ice and lakes; soil
      and sediments; and organisms and biomarkers.

PMID- 25395124
TI  - Investigation of isomeric flavanol structures in black tea thearubigins using
      ultraperformance liquid chromatography coupled to hybrid quadrupole/ion
      mobility/time of flight mass spectrometry.
AB  - Ultra performance liquid chromatography (UPLC) when coupled to ion mobility
      (IMS)/orthogonal acceleration time of flight mass spectrometry is a suitable
      technique for analyzing complex mixtures such as the black tea thearubigins. With
      the aid of this advanced instrumental analysis, we were able to separate and
      identify different isomeric components in the complex mixture which could
      previously not be differentiated by a conventional high performance liquid
      chromatography/tandem mass spectrometry. In this study, the difference between
      isomeric structures theasinensins, proanthocyanidins B-type and rutin (quercetin
      3O-rutinoside) were studied, and these are present abundantly in many botanical
      sources. The differentiation between these structures was accomplished according
      to their acquired mobility drift times differing from the traditional
      investigations in mass spectrometry, where calculation of theoretical collisional
      cross sections allowed assignment of the individual isomeric structures. The
      present work demonstrates UPLC-IMS-MS as an efficient technology for isolating
      and separating isobaric and isomeric structures existing in complex mixtures
      discriminating between them according to their characteristic fragment ions and
      mobility drift times. Therefore, a rational assignment of isomeric structures in
      many phenolic secondary metabolites based on the ion mobility data might be
      useful in mass spectrometry-based structure analysis in the future.

PMID- 25395125
TI  - Determination of polychlorinated biphenyls by liquid chromatography-atmospheric
      pressure photoionization-mass spectrometry.
AB  - This study presents the atmospheric pressure photoionization (APPI) of high
      chlorinated (five or more chlorine atoms) polychlorinated biphenyls (PCBs) using
      toluene as dopant, after liquid chromatographic separation. Mass spectra of PCB
      101, 118, 138, 153, 180, 199, 206 and 209 were recorded by using liquid
      chromatography-APPI-tandem mass spectrometry (LC-APPI-MS/MS) in negative ion full
      scan mode. Intense peaks appeared at m/z that correspond to [M - Cl + O](-) ions,
      where M is the analyte molecule. Furthermore, a detailed strategy, which includes
      designs of experiments, for the development and optimization of LC-APPI-MS/MS
      methods is described. Following this strategy, a sensitive and accurate method
      with low instrumental limits of detection, ranging from 0.29 pg for PCB 209 to
      8.3 pg for PCB 101 on column, was developed. For the separation of the analytes,
      a Waters XSELECT HSS T3 (100 mm * 2.1 mm, 2.5 um) column was used with
      methanol/water as elution system. This method was applied for the determination
      of the above PCBs in water samples (surface water, tap water and treated
      wastewater). For the extraction of PCBs from water samples, a simple liquid
      liquid extraction with dichloromethane was used. Method limits of quantification,
      ranged from 4.8 ng l(-1), for PCB 199, to 9.4 ng l(-1), for PCB 180, and the
      recoveries ranged from 73%, for PCB 101, to 96%, for PCB 199. The estimated
      analytical figures were appropriate for trace analysis of high-chlorinated PCBs
      in real samples.

PMID- 25395126
TI  - Characterization of metabolites of sweroside in rat urine using ultra-high
      performance liquid chromatography combined with electrospray ionization
      quadrupole time-of-flight tandem mass spectrometry and NMR spectroscopy.
AB  - Sweroside, a major active iridoid in Swertia pseudochinensis Hara, is recognized
      as an effective agent in the treatment of liver injury. Based on previous
      reports, the relatively short half-life (64 min) and poor bioavailability
      (approximately 0.31%) in rats suggested that not only sweroside itself but also
      its metabolites could be responsible for the observed hepato-protective effect.
      However, few studies have been carried out on the metabolism of sweroside.
      Therefore, the present study aimed at identifying the metabolites of sweroside in
      rat urine after a single oral dose (100 mg/kg). With ultra-high-performance
      liquid chromatography coupled with electrospray ionization quadrupole time-of
      flight tandem mass spectrometry (UHPLC/Q-TOF-MS), the metabolic profile revealed
      11 metabolites in rat urine, including phase I, phase II and aglycone-related
      products. The chemical structures of metabolites were proposed based on accurate
      mass measurements of protonated or deprotonated molecules and their fragmentation
      patterns. Our findings showed that the aglycone of sweroside (M05) and its
      glucuronide conjugate (M06) were principal circulating metabolites in rats. While
      several other metabolic transformations, occurring via reduction, N
      heterocyclization and N-acetylation after deglycosylation, were also observed.
      Two metabolites (M05 and M06) were isolated from the rat urine for structural
      elucidation and identifcation of reaction sites. Both M05 and M06 were
      characterized by (1)H, (13)C and two-dimensional nuclear magnetic resonance (NMR)
      spectroscopy. UHPLC/Q-TOF-MS analysis has provided an important analytical
      platform to gather metabolic profile of sweroside.

PMID- 25395127
TI  - Dereplication of Streptomyces sp. AMC 23 polyether ionophore antibiotics by
      accurate-mass electrospray tandem mass spectrometry.
AB  - Actinomycetes, especially those belonging to the genus Streptomyces, are
      economically important from a biotechnological standpoint: they produce
      antibiotics, anticancer compounds and a variety of bioactive substances that are
      potentially applicable in the agrochemical and pharmaceutical industries. This
      paper combined accurate-mass electrospray tandem mass spectrometry in the full
      scan and product ion scan modes with compounds library data to identify the major
      compounds in the crude extract produced by Streptomyces sp. AMC 23; it also
      investigated how sodiated nonactin ([M + Na](+)) fragmented. Most product ions
      resulted from elimination of 184 mass units due to consecutive McLafferty-type
      rearrangements. The data allowed identification of four macrotetrolides
      homologous to nonactin (monactin, isodinactin, isotrinactin/trinactin and
      tetranactin) as well as three related linear dimer compounds (nonactyl
      nonactoate, nonactyl homononactoate and homononactyl homononactoate). The major
      product ions of the sodiated molecules of these compounds also originated from
      elimination of 184 and 198 mass units. UPLC-MS/MS in the neutral loss scan mode
      helped to identify these compounds on the basis of the elimination of 184 and 198
      mass units. This method aided monitoring of the relative production of these
      compounds for 32 days and revealed that the biosynthetic process began with
      increased production of linear dimers as compared with macrotetrolides. These
      data could facilitate dereplication and identification of these compounds in
      other microbial crude extracts.

PMID- 25395128
TI  - Ultraviolet laser desorption/ionization mass spectrometry of single-core and
      multi-core polyaromatic hydrocarbons under variable conditions of collisional
      cooling: insights into the generation of molecular ions, fragments and oligomers.
AB  - The ultraviolet laser desorption/ionization of polyaromatic hydrocarbons (PAHs)
      has been investigated under different background pressures of an inert gas (up to
      1.2 mbar of N2) in the ion source of a hybrid, orthogonal-extracting time-of
      flight mass spectrometer (oTOF-MS). The study includes an ensemble of six model
      PAHs with isolated single polyaromatic cores and four ones with multiple cross
      linked aromatic and polyaromatic cores. In combination with a weak ion extraction
      field, the variation of the buffer gas pressure allowed to control the degree of
      collisional cooling of the desorbed PAHs and, thus, to modulate their
      decomposition into fragments. The dominant fragmentation channels observed are
      related to dehydrogenation of the PAHs, in most cases through the cleavage of
      even numbers of C-H bonds. Breakage of C-C bonds leading to the fragmentation of
      rings, side chains and core linkages is also observed, in particular, at low
      buffer gas pressures. The precise patterns of the combined fragmentation
      processes vary significantly between the PAHs. The highest abundances of
      molecular PAH ions and cleanest mass spectra were consistently obtained at the
      highest buffer gas pressure of 1.2 mbar. The effective quenching of the
      fragmentation pathways at this elevated pressure improves the sensitivity and
      data interpretation for analytical applications, although the fragmentation of
      side chains and of bonds between (poly)aromatic cores is not completely
      suppressed in all cases. Moreover, these results suggest that the detected
      fragments are generated through thermal equilibrium processes rather than as a
      result of rapid photolysis. This assumption is further corroborated by a laser
      desorption/ionization post-source decay analysis using an axial time-of-flight
      MS. In line with these findings, covalent oligomers of the PAHs, which are
      presumably formed by association of two or more dehydrogenated fragments, are
      detected with higher abundances at the lower buffer gas pressures.

PMID- 25395129
TI  - The unexpected formation of [M - H]+ species during MALDI and dopant-free APPI MS
      analysis of novel antineoplastic curcumin analogues.
AB  - Unusual ionization behavior was observed with novel antineoplastic curcumin
      analogues during the positive ion mode of matrix-assisted laser desorption
      ionization (MALDI) and dopant-free atmospheric pressure photoionization (APPI).
      The tested compounds produced an unusual significant peak designated as [M -
      H](+) ion along with the expected [M + H](+) species. In contrast, electrospray
      ionization, atmospheric pressure chemical ionization and the dopant-mediated APPI
      (dopant-APPI) showed only the expected [M + H](+) peak. The [M - H](+) ion was
      detected with all evaluated curcumin analogues including phosphoramidates,
      secondary amines, amides and mixed amines/amides. Our experiments revealed that
      photon energy triggers the ionization of the curcumin analogues even in the
      absence of any ionization enhancer such as matrix, solvent or dopant. The
      possible mechanisms for the formation of both [M - H](+) and [M + H](+) ions are
      discussed in this paper. In particular, three proposed mechanisms for the
      formation of [M - H](+) were evaluated. The first mechanism involves the loss of
      H2 from the protonated [M + H](+) species. The other two mechanisms include
      hydrogen transfer from the analyte radical cation or hydride abstraction from the
      neutral analyte molecule.

PMID- 25395130
TI  - Mass spectrometric detection, identification, and fragmentation of arseno
      phytochelatins.
AB  - Phytochelatins (PC) are cystein-rich oligopeptides in plants for coordination
      with toxic metals and metalloids via their thiol groups. The composition,
      structure, and mass spectrometric fragmentation of arseno-PC (As-PC) with PC of
      different degree of oligomerization (PC2-PC5) in solution were studied using
      liquid chromatography coupled in parallel to inductively coupled plasma mass
      spectrometry and electrospray ionization quadrupole time-of-flight mass
      spectrometry. As-PC were detected from As(PC2) to As(PC5) with an increasing
      number of isomers that differ in the position of thiol groups bound to As.
      Thermodynamic modeling supported the identification process in case of these
      isomers. Mass spectrometric fragmentation of the As-PC does not follow the
      established pattern of peptides but is governed by the formation of series of As
      containing annular cations, which coordinate to As via S, N, or O. Structure
      proposals for 30 As-PC fragment ions in the range m/z 147.92 to m/z 1290.18 are
      elaborated. Many of these fragment ions are characteristic to several As-PC and
      may be suited for a screening for As-PC in plant extracts. The mass spectrometric
      data offer the perspective for a future more sensitive determination of As-PC by
      means of liquid chromatography tandem mass spectrometry with multiple reaction
      monitoring.

PMID- 25395131
TI  - The mass spectrometric study on aminohydroxamic acids-based metallacrowns.
AB  - Electrospray ionization mass spectrometry (MS) has been widely used to detect
      noncovalent interactions in supramolecular compounds, especially in biological
      systems. In our work, we present the application of the electrospray ionization
      MS technique to characterize the metallamacrocycles, known as metallacrowns. This
      project involves investigations of the aminohydroxamic acids structure and
      chirality influence on formation of ternary 12-metallacrown-4 complexes. For our
      experiments, we used a series of beta-aminohydroxamic acids and derivatives of
      histidinehydroxamic acid. A high stability of the studied supramolecular systems
      in the gas phase was confirmed by MS/MS experiments. We also proposed the
      fragmentation pathways for the studied compounds. Obtained results reveal that
      the ternary 12-metallacrown-4 formation process is not selective, and ligands of
      various structures and chiralities can be incorporated into these systems.

PMID- 25395132
TI  - VUV photodissociation of thiazole molecule investigated by TOF-MS and
      photoelectron photoion coincidence spectroscopy.
AB  - Photoelectron photoion coincidence measurements have been performed for the
      thiazole (C3H3NS) molecule in gas phase, using time-of-flight mass spectrometry
      in the electron-ion coincidence mode and vacuum ultraviolet synchrotron
      radiation. photoelectron photoion coincidence spectra have been recorded as a
      function of the photon energy covering the valence range from 10 to 21 eV. The
      resulting photoionization products as well as the dissociation pathways leading
      to the ionic species were proposed and discussed. We have also performed density
      functional theory and ab initio calculations for the neutral molecule, its cation
      and the ion fragments produced in order to determine their electronic and
      structural parameters.

PMID- 25395133
TI  - The development and assessment of high-throughput mass spectrometry-based methods
      for the quantification of a nanoparticle drug delivery agent in cellular lysate.
AB  - The safe use of lipid-based drug delivery agents requires fast and sensitive
      qualitative and quantitative assessment of their cellular interactions. Many mass
      spectrometry (MS) based analytical platforms can achieve such task with varying
      capabilities. Therefore, four novel high-throughput MS-based quantitative methods
      were evaluated for the analysis of a small organic gene delivery agent: N,N
      bis(dimethylhexadecyl)-1,3-propane-diammonium dibromide (G16-3). Analysis
      utilized MS instruments that detect analytes using low-resolution tandem MS
      (MS/MS) analysis (i.e. QTRAP or linear ion trap in this work) or high-resolution
      MS analysis (i.e. time of flight (ToF) or Orbitrap). Our results indicate that
      the validated fast chromatography (FC)-QTRAP-MS/MS, FC- LTQ-Orbitrap-MS,
      desorption electrospray ionization-collision-induced dissociation (CID)-MS/MS and
      matrix assisted laser desorption ionization-ToF/ToF-MS MS methods were superior
      in the area of method development and sample analysis time to a previously
      developed liquid chromatography (LC)-CID-MS/MS. To our knowledge, this is the
      first evaluation of the abilities of five MS-based quantitative methods that
      target a single pharmaceutical analyte. Our findings indicate that, in comparison
      to conventional LC-CID-MS/MS, the new MS-based methods resulted in a (1)
      substantial reduction in the analysis time, (2) reduction in the time required
      for method development and (3) production of either superior or comparable
      quantitative data. The four new high-throughput MS methods, therefore, were
      faster, more efficient and less expensive than a conventional LC-CID-MS/MS for
      the quantification of the G16-3 analyte within tissue culture. When applied to
      cellular lysate, no significant change in the concentration of G16-3 gemini
      surfactant within PAM212 cells was observed between 5 and 53 h, suggesting the
      absence of any metabolism/excretion from PAM212 cells.

PMID- 25395134
TI  - Atmospheric pressure gas chromatography coupled to quadrupole-time of flight mass
      spectrometry as a tool for identification of volatile migrants from autoadhesive
      labels used for direct food contact.
AB  - Pressure-sensitive adhesives (PSA) are used to manufacture labels that are
      applied directly on the food. These adhesives could contain not only
      intentionally added compounds (IAS) to the adhesive formula but also non
      intentionally added substances (NIAS), due to the impurities from the raw
      materials used, decomposition of the initial components or from chemical
      interactions between them. These compounds could migrate to the food and
      contaminate it. In this study, gas chromatography coupled with mass spectrometry
      (GC-MS/Q) and atmospheric pressure gas chromatography coupled to a quadrupole
      hyphenated to a time of flight mass spectrometer (APGC-MS/Q-TOF) have been used
      for identification of unknown compounds and NIAS coming from a PSA. Seven
      compounds were identified by GC-MS/Q, and other eight compounds remained
      initially unknown. The structure of these eight new compounds was elucidated by
      working with the spectra obtained by APGC-MS/Q-TOF. Finally, two different
      migration studies were carried out. The first one with Tenax as solid food
      simulant in contact with the paper label containing the adhesive and the second
      one with isooctane filled in a natural pork intestine where the label containing
      the adhesive was applied on the external side. The results are shown and
      discussed.

PMID- 25395135
TI  - Identification of RNA sequence isomer by isotope labeling and LC-MS/MS.
AB  - Recently, we developed a method for modified ribonucleic acid (RNA) analysis
      based on the comparative analysis of RNA digests (CARD). Within this CARD
      approach, sequence or modification differences between two samples are identified
      through differential isotopic labeling of two samples. Components present in both
      samples will each be labeled, yielding doublets in the CARD mass spectrum.
      Components unique to only one sample should be detected as singlets. A limitation
      of the prior singlet identification strategy occurs when the two samples contain
      components of unique sequence but identical base composition. At the first stage
      of mass spectrometry, these sequence isomers cannot be differentiated and would
      appear as doublets rather than singlets. However, underlying sequence differences
      should be detectable by collision-induced dissociation tandem mass spectrometry
      (CID MS/MS), as y-type product ions will retain the original enzymatically
      incorporated isotope label. Here, we determine appropriate instrumental
      conditions that enable CID MS/MS of isotopically labeled ribonuclease T1 (RNase
      T1) digestion products such that the original isotope label is maintained in the
      product ion mass spectrum. Next, we demonstrate how y-type product ions can be
      used to differentiate singlets and doublets from isomer sequences. We were then
      able to extend the utility of this approach by using CID MS/MS for the
      confirmation of an expected RNase T1 digestion product within the CARD analysis
      of an Escherichia coli mutant strain even in the presence of interfering and
      overlapping digestion products from other transfer RNAs.

PMID- 25395136
TI  - Effective methods for the measurement of CsI cluster ions using MALDI-MS with
      suitable solvent combinations and additives.
AB  - A method to measure CsI cluster ions ((CsI)(n)Cs(+), (CsI)(n)I(-)) from CsI
      samples in matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) was developed with a 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]
      malononitrile (DCTB) matrix and additives. Solvent combinations in which the CsI
      and DCTB solutions were miscible were effective in detecting CsI cluster ions at
      a mass range of over m/z 2000 and are associated with a characteristic spread of
      DCTB within the CsI/DCTB mixture. The addition of saccharides or sugar alcohols
      to the CsI/DCTB mixture improved the DCTB distribution and widened the mass
      distribution of CsI cluster ions up to m/z 10,000 in the linear mode.

PMID- 25395139
TI  - Engraftment's Holy Grail: is one signal enough?
AB  - In this issue of Blood, Ramos-Mejia et al provide compelling evidence for HOXA9
      as a key factor that can enhance and accelerate the differentiation of these
      cells to blood progenitor cells in vitro.

PMID- 25395140
TI  - How to generate large numbers of CD103+ dendritic cells.
AB  - In this issue of Blood, Mayer et al describe a new method of generating high
      numbers of Batf3- and Irf8-dependent CD103+ conventional dendritic cells (cDCs),
      providing new opportunities to study this subset of antigen-presenting cells
      specialized in crosspresentation.

PMID- 25395141
TI  - HiJAKing T-ALL.
AB  - In the current issue of Blood, Degryse and coauthors report the transforming
      potential of a series of JAK3 mutations identified in primary T-cell acute
      lymphoblastic leukemia (T-ALL) samples and pave the way toward multitargeted JAK1
      and JAK3 therapy in T-ALL.

PMID- 25395142
TI  - Stress equips CLL cells to survive.
AB  - In this issue of Blood, Krysov et al demonstrate that B-cell receptor (BCR)
      signaling in chronic lymphocytic leukemia (CLL) results in partial activation of
      the unfolded protein response (UPR).

PMID- 25395143
TI  - Cautious enthusiasm about GWAS findings.
AB  - In this issue of Blood, Ma and colleagues report the first agnostic investigation
      by a genome-wide association study (GWAS) in search of genetic determinants of a
      variation in plasma plasminogen levels.

PMID- 25395144
TI  - Valuing Stillbirths.
AB  - Estimates of the burden of disease assess the mortality and morbidity that affect
      a population by producing summary measures of health such as quality-adjusted
      life years (QALYs) and disability-adjusted life years (DALYs). These measures
      typically do not include stillbirths (fetal deaths occurring during the later
      stages of pregnancy or during labor) among the negative health outcomes they
      count. Priority-setting decisions that rely on these measures are therefore
      likely to place little value on preventing the more than three million
      stillbirths that occur annually worldwide. In contrast, neonatal deaths, which
      occur in comparable numbers, have a substantial impact on burden of disease
      estimates and are commonly seen as a pressing health concern. In this article we
      argue in favor of incorporating unintended fetal deaths that occur late in
      pregnancy into estimates of the burden of disease. Our argument is based on the
      similarity between late-term fetuses and newborn infants and the assumption that
      protecting newborns is important. We respond to four objections to counting
      stillbirths: (1) that fetuses are not yet part of the population and so their
      deaths should not be included in measures of population health; (2) that valuing
      the prevention of stillbirths will undermine women's reproductive rights; (3)
      that including stillbirths implies that miscarriages (fetal deaths early in
      pregnancy) should also be included; and (4) that birth itself is in fact
      ethically significant. We conclude that our proposal is ethically preferable to
      current practice and, if adopted, is likely to lead to improved decisions about
      health spending. 

PMID- 25395145
TI  - Laparoscopic evacuation of mucinous ascites for palliation of pseudomyxoma
      peritonei.
AB  - INTRODUCTION: Accumulation of mucinous ascites causes significant morbidity for
      patients with unresectable pseudomyxoma peritonei (PMP). The success of
      paracentesis for mucin evacuation is limited due to the presence of adhesions,
      disease burden, and the viscous nature of mucinous ascites. We sought to review
      our experience with laparoscopic evacuation of mucinous ascites for palliation of
      PMP. METHODS: Records were reviewed for patients who underwent laparoscopy for
      carcinomatosis secondary to appendix or colon cancer from July 2007 to January
      2014. Of 123 patients, 10 were identified who underwent 17 laparoscopic
      procedures for palliative evacuation of mucinous ascites. RESULTS: All patients
      had primary appendiceal cancers and all presented with symptomatic ascites
      causing abdominal distension and bloating. Pneumoperitoneum was established with
      a Veress needle or 5-mm optical viewing trocar in the majority of cases (n = 11).
      In the remaining six cases, an open technique was used and a 10-mm Hasson trocar
      was placed. There were no trocar-related complications. The median volume of
      mucin evacuated was 2.0 liters (range 1.7-8.0). All procedures were done as same
      day surgeries; no patients required hospitalization. All patients reported
      symptomatic improvement following the procedure. One patient experienced a grade
      1 complication of persistent drainage from one incision, which was managed in the
      outpatient setting. The median follow-up for all pts was 9.1 months. The median
      time to recurrent symptoms requiring repeat intervention was 5.3 months.
      CONCLUSIONS: Laparoscopic evacuation of mucinous ascites for select patients with
      PMP is feasible and results in significant, durable symptom control with minimal
      morbidity.

PMID- 25395146
TI  - Histologic categorization of desmoplastic reaction: its relevance to the
      colorectal cancer microenvironment and prognosis.
AB  - BACKGROUND: Although the essential roles of stromata in tumor development have
      been recognized, the morphologic classification of desmoplastic reaction (DR) in
      colorectal cancer (CRC) is unclear. METHODS: In this study, DRs were
      histologically classified into three patterns based on the products of activated
      fibroblasts (i.e., keloid-like collagen and myxoid stroma). The prognostic impact
      of DRs was evaluated in two independent cohorts of stages 2 and 3 CRC patients:
      cohort 1 (880 patients) and cohort 2 (474 patients). The association of DR and
      the local environment was investigated immunohistochemically. RESULTS: In cohort
      1, mature DR was shown by 413 patients, intermediate DR by 275 patients, and
      immature DR by 192 patients. Categorization of DR was significantly associated
      with tumor location, pT and pN stages, tumor differentiation, venous invasion,
      tumor budding, and Crohn's-like lymphoid reaction (P <= 0.0001-0.008). Immature
      DR was relevant to the high incidence of recurrence in the liver, lung, lymph
      nodes, peritoneum, and locoregional areas (P <= 0.0001-0.002). The 5-year disease
      free survival rate was highest in the mature group (87 %), followed by the
      intermediate group (72 %) and the immature group (49 % (P < 0.0001). In the
      multivariate analysis, DR showed an impact on survival outcome independent of
      conventional prognostic factors, including pT and pN stages. These results were
      similarly observed in cohort 2. Immature DR was associated with normal MutL
      homologue 1 (MLH1)/MutS homologue 2 (MSH2) immunoreactivity, a smaller number of
      infiltrating CD8(+) T cells and tumor-associated macrophages, a decreased
      microvessel count, and positive expression of tenascin-C and fibronectin.
      CONCLUSION: The proposed histologic DR categorization directly reflects tumor
      behavior in a modulating stromal environment and could provide valuable
      prognostic information for CRC patients.

PMID- 25395147
TI  - Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C
      Hepatocellular Carcinoma Undergoing Hepatic Resection.
AB  - BACKGROUND: Although the prevalence of non-B non-C hepatocellular carcinoma (NBNC
      HCC) has increased, its clinicopathologic characteristics remain unclear.
      METHODS: We retrospectively analyzed 518 HCC patients who underwent hepatic
      resection. Hepatitis B surface antigen- and hepatitis C antibody-negative
      patients were categorized into the NBNC HCC group (n = 145); others were
      categorized into the hepatitis B or C HCC (BC HCC) group (n = 373). We subdivided
      the etiologies of NBNC HCC according to alcohol intake and presence of steatosis.
      RESULTS: NBNC HCC was associated with nonalcoholic fatty liver disease (NAFLD)
      (13.1 %), fatty liver disease with moderate alcohol intake (9.0 %), alcoholic
      liver disease (ALD) (29.7 %), cryptogenic disease (44.1 %), and other known
      etiologies (4.1 %). The prevalence of obesity, diabetes mellitus, and
      hypertension was higher and hepatic function was better in the NBNC HCC group,
      which had significantly larger tumors than the BC HCC group. The entire NBNC HCC
      group displayed similar overall and disease-free survival as the BC HCC group.
      Among the subdivisions, NAFLD-associated HCC patients had significantly better
      disease-free survival than ALD-associated HCC and BC HCC patients. Microvascular
      invasion (hazard ratio [HR] 2.30; 95 % confidence interval [CI] 1.33-3.96) and
      steatosis area <5 % of noncancerous region (HR 2.13; 95 % CI 1.21-3.93) were
      associated with disease-free survival in NBNC HCC patients. CONCLUSIONS: The
      prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients,
      NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of
      steatosis in hepatic parenchyma had a significant impact on disease-free survival
      in NBNC HCC patients.

PMID- 25395148
TI  - Carbon dioxide pneumoperitoneum led to no severe morbidities for the elderly
      during laparoscopic-assisted distal gastrectomy.
AB  - BACKGROUND: Our purpose was to evaluate the perioperative safety of laparoscopic
      assisted distal gastrectomy (LADG) in elderly patients with clinical stage I
      gastric cancer. METHODS: From 527 consecutive patients who underwent distal
      gastrectomy for gastric cancer from 2000 to 2011, 38 elderly patients (aged 75
      years or older) with clinical stage I disease who underwent LADG were compared
      with 28 elderly patients who underwent open distal gastrectomy (ODG) and with 41
      nonelderly patients (younger than aged 65 years) who underwent LADG.
      Intraoperative cardiopulmonary changes following pneumoperitoneum and surgical
      outcomes were analyzed. RESULTS: A significant elevation in mean blood pressure
      (MAP) (by 44 %) and slight increase in heart rate (HR) (by 13 %) were observed 5
      min after the beginning of pneumoperitoneum in the elderly LADG group, although
      they tended to remain stable since 30 min. The elevation of end-tidal CO2 (ETCO2)
      in the elderly LADG group remained at 8 % and did not differ from that in the
      nonelderly LADG group who were 20.5 years (median) younger, whereas percutaneous
      oxygen saturation (SpO2) did not worsen. Compared with the elderly ODG group, the
      elderly LADG group did not increase intraoperative cardiopulmonary impairment or
      complication, had lower incidence of postoperative medical complication (7.9 vs.
      32.1 %, p = 0.012) and shortened postoperative recovery course (25 vs. 15 days, p
      < 0.001). Pneumoperitoneum did not necessarily impair cardiopulmonary dynamics or
      prognosis for elderly patients with declining cardiopulmonary function.
      CONCLUSIONS: Cardiopulmonary impairment caused by pneumoperitoneum was not
      critical but transitory. LADG led to superior perioperative course for elderly
      patients with early gastric cancer.

PMID- 25395149
TI  - Does the Difference of Invasiveness between Totally Laparoscopic Distal
      Gastrectomy and Laparoscopy-Assisted Distal Gastrectomy Lead to a Difference in
      Early Surgical Outcomes? A Prospective Randomized Trial.
AB  - BACKGROUND: Resection and anastomosis in laparoscopic distal gastrectomy can be
      performed extracorporeally or intracorporeally. Most surgeons have performed
      laparoscopy-assisted distal gastrectomy (LADG) because of technical difficulties
      of intracorporeal anastomosis. However, totally laparoscopic distal gastrectomy
      (TLDG) has recently been attempted and is expected to be feasible and less
      invasive compared with LADG. In this study, we tried to evaluate the clinical
      effect of the difference of invasiveness between TLDG and LADG, by way of a
      randomized prospective trial. METHODS: From February 2011 to September 2013, a
      total of 110 patients with primary gastric cancer were randomly assigned to
      either TLDG or LADG. Clinicopathologic features, operative details, postoperative
      course, and quality of life (QoL) were compared between the two groups. QoL was
      assessed using the European Organisation for Research and Treatment of Cancer
      Quality of Life Questionnaire-C30 and gastric module STO22 at 2 weeks and 3
      months after surgery. RESULTS: The two groups were comparable in clinical and
      pathological characteristics. The proximal resection margin was significantly
      longer and the length of wound was shorter in the TLDG group. We could not find
      any significant difference in postoperative inflammatory parameters,
      postoperative pulmonary function, postoperative recovery, and QoL scores at 2
      weeks and 3 months after surgery. There were no significant differences in
      complication rates. CONCLUSIONS: This study suggests that TLDG is as safe and
      feasible as LADG in gastric cancer. The parameters used routinely in the clinical
      field to evaluate early surgical outcomes could not reflect the delicate
      difference in surgical invasiveness between TLDG and LADG.

PMID- 25395150
TI  - Low Lymph Node Retrieval After Preoperative Chemoradiation for Rectal Cancer is
      Associated with Improved Prognosis in Patients with a Good Tumor Response.
AB  - PURPOSE: To examine the association between the number of lymph nodes retrieved
      and oncologic outcome after preoperative chemoradiation for rectal cancer
      according to tumor regression grade. METHODS: Patients with rectal cancer who
      underwent curative surgery between May 2004 and December 2012 were analyzed
      retrospectively. Using multivariate analysis, the correlation between
      clinicopathologic variables and the number of lymph nodes retrieved was
      evaluated. The associations between the oncologic outcome and number of lymph
      nodes retrieved were also investigated according to the tumor regression grade.
      RESULTS: In total, 1,332 patients were identified, of whom 433 (32.8 %) received
      preoperative chemoradiation. Multivariate analysis revealed that preoperative
      chemoradiation was an independent predictor of the number of lymph nodes
      retrieved (P = 0.002). After chemoradiation, the number of total and positive
      lymph nodes retrieved was inversely correlated with tumor regression. Retrieval
      of >=12 lymph nodes was not an independent prognostic factor for disease-free
      survival; however, among patients with a good tumor response, those with <12
      lymph nodes retrieved had a significantly better 3-year disease-free survival (P
      = 0.030) than those with >=12 lymph nodes retrieved. CONCLUSIONS: Reduced lymph
      node yield after preoperative chemoradiation for rectal cancer does not indicate
      inadequate oncologic surgery. It may represent good treatment response and better
      prognosis, especially in patients with good pathologic tumor regression after
      chemoradiation.

PMID- 25395151
TI  - Social ecology of the classroom: issues of inclusivity.

PMID- 25395152
TI  - Erratum to: A new window to understanding individual differences in reward
      sensitivity from attentional networks.

PMID- 25395153
TI  - Transgenerational sex-specific impact of preconception stress on the development
      of dendritic spines and dendritic length in the medial prefrontal cortex.
AB  - Perinatal adverse experience programs social and emotional behavioral traits and
      is a major risk factor for the development of behavioral and psychiatric
      disorders. Little information is available on how adversity to the mother prior
      to her first pregnancy (preconception stress, PCS) may affect brain structural
      development, which may underlie behavioral dysfunction in the offspring.
      Moreover, little is known about possible sex-dependent consequences of PCS in the
      offspring. This study examined spine number/density and dendritic
      length/complexity of layer II/III pyramidal neurons in the anterior cingulate
      (ACd), prelimbic/infralimbic (PL/IL) and orbitofrontal cortex (OFC) of male and
      female rats born to mothers exposed to unpredictable variable stress at different
      time points prior to reproduction. Our main findings are that in line with our
      hypothesis adversity to the mother before her pregnancy results in highly complex
      changes in neuronal morphology in the medial prefrontal, but not in the
      orbitofrontal cortical regions of her future offspring that persist into
      adulthood. Moreover, our study revealed that (1) in the PCS2 group (offspring of
      dams mated two weeks after stress) spine numbers and dendritic length and
      complexity were increased in response to PCS in the ACd and PL/IL, (2) these
      regional effects depended on the temporal proximity of adversity and conception,
      (3) in the ACd of the PCS2 group only males and the left hemispheres were
      affected. We speculate that these transgenerational brain structural changes are
      mediated by stress-induced epigenetic (re)programming of future gene activity in
      the oocyte. 

PMID- 25395154
TI  - Adult right living-donor liver transplantation with special reference to
      reconstruction of the middle hepatic vein.
AB  - Two hundred fifty-three consecutive living-donor liver transplant recipients with
      a right liver graft (RLG) were divided into three groups: an extended right liver
      graft (ERLG) group (n = 47) in which the middle hepatic vein (MHV) trunk was
      included in the graft, a modified right liver graft (MRLG) group (n = 114) in
      which the MHV tributaries were reconstructed with cryopreserved homologous veins
      and a simple RLG group (n = 92) in which the MHV tributaries were sacrificed. The
      volume of the anterior sector was significantly impaired in the RLG group
      compared to the other two groups, whereas the volume of the posterior sector was
      significantly improved in the RLG group, indicating that the impaired anterior
      sector regeneration by MHV deprivation was compensated by the posterior sector
      regeneration. The regeneration rate of the anterior sector was highest in the
      ERLG group (92%), moderate in the MRLG group (71%) and lowest in the RLG group
      (52%). The whole graft regeneration rate of the ERLG group was significantly
      higher than that of the other two groups. Poor regeneration, however, was not
      correlated with delayed functional recovery or long-term outcome. Short-term, the
      patency of reconstructed MHV tributaries was over 90%, but occlusion occurred
      frequently over the long-term, especially in V5. 

PMID- 25395155
TI  - The moderating and mediating roles of self-acceptance and tolerance to others in
      the relationship between mindfulness and subjective well-being.
AB  - This study explored the moderating and mediating influences of self-acceptance
      and tolerance to others in the relationship between mindfulness and subjective
      well-being. In total, 301 (130 males) university students completed the Five
      Facet Mindfulness Questionnaire, Index of Well-being, Self-acceptance
      Questionnaire, and Tolerance Scale. The results showed that the positive link
      between mindfulness and subjective well-being was significantly mediated by self
      acceptance only. Tolerance played a moderating role. The implications of the
      results for relevant research and mindfulness training were discussed.

PMID- 25395156
TI  - Limits in virus filtration capability? Impact of virus quality and spike level on
      virus removal with xenotropic murine leukemia virus.
AB  - Virus filtration (VF) is a key step in an overall viral clearance process since
      it has been demonstrated to effectively clear a wide range of mammalian viruses
      with a log reduction value (LRV) > 4. The potential to achieve higher LRV from
      virus retentive filters has historically been examined using bacteriophage
      surrogates, which commonly demonstrated a potential of > 9 LRV when using high
      titer spikes (e.g. 10(10) PFU/mL). However, as the filter loading increases, one
      typically experiences significant decreases in performance and LRV. The 9 LRV
      value is markedly higher than the current expected range of 4-5 LRV when
      utilizing mammalian retroviruses on virus removal filters (Miesegaes et al., Dev
      Biol (Basel) 2010;133:3-101). Recent values have been reported in the literature
      (Stuckey et al., Biotech Progr 2014;30:79-85) of LRV in excess of 6 for PPV and
      XMuLV although this result appears to be atypical. LRV for VF with therapeutic
      proteins could be limited by several factors including process limits (flux
      decay, load matrix), virus spike level and the analytical methods used for virus
      detection (i.e. the Limits of Quantitation), as well as the virus spike quality.
      Research was conducted using the Xenotropic-Murine Leukemia Virus (XMuLV) for its
      direct relevance to the most commonly cited document, the International
      Conference of Harmonization (ICH) Q5A (International Conference on Harmonisation
      of Technical Requirements for Registration of Pharmaceuticals for Human Use,
      Geneva, Switzerland, 1999) for viral safety evaluations. A unique aspect of this
      work is the independent evaluation of the impact of retrovirus quality and virus
      spike level on VF performance and LRV. The VF studies used XMuLV preparations
      purified by either ultracentrifugation (Ultra 1) or by chromatographic processes
      that yielded a more highly purified virus stock (Ultra 2). Two monoclonal
      antibodies (Mabs) with markedly different filtration characteristics and with
      similar levels of aggregate (<1.5%) were evaluated with the Ultra 1 and Ultra 2
      virus preparations utilizing the Planova 20 N, a small virus removal filter.
      Impurities in the virus preparation ultimately limited filter loading as measured
      by determining the volumetric loading condition where 75% flux decay is observed
      versus initial conditions (V75). This observation occurred with both Mabs with
      the difference in virus purity more pronounced when very high spike levels were
      used (>5 vol/vol %). Significant differences were seen for the process
      performance over a number of lots of the less-pure Ultra 1 virus preparations.
      Experiments utilizing a developmental lot of the chromatographic purified XMuLV
      (Ultra 2 Development lot) that had elevated levels of host cell residuals (vs.
      the final Ultra 2 preparations) suggest that these contaminant residuals can
      impact virus filter fouling, even if the virus prep is essentially monodisperse.
      Process studies utilizing an Ultra 2 virus with substantially less host cell
      residuals and highly monodispersed virus particles demonstrated superior
      performance and an LRV in excess of 7.7 log10 . A model was constructed
      demonstrating the linear dependence of filtration flux versus filter loading
      which can be used to predict the V75 for a range of virus spike levels conditions
      using this highly purified virus. Fine tuning the virus spike level with this
      model can ultimately maximize the LRV for the virus filter step, essentially
      adding the LRV equivalent of another process step (i.e. protein A or CEX
      chromatography).

PMID- 25395157
TI  - Author's reply: To PMID 24938629.

PMID- 25395158
TI  - Role of desmoplakin mutations in the pathogenesis of non-compaction.

PMID- 25395159
TI  - Real-time monitoring system for improving corona electrostatic separation in the
      process of recovering waste printed circuit boards.
AB  - Although corona electrostatic separation is successfully used in recycling waste
      printed circuit boards in industrial applications, there are problems that cannot
      be resolved completely, such as nonmetal particle aggregation and spark
      discharge. Both of these problems damage the process of separation and are not
      easy to identify during the process of separation in industrial applications.
      This paper provides a systematic study on a real-time monitoring system. Weight
      monitoring systems were established to continuously monitor the separation
      process. A Virtual Instrumentation program written by LabVIEW was utilized to
      sample and analyse the mass increment of the middling product. It includes four
      modules: historical data storage, steady-state analysis, data computing and
      alarm. Three kinds of operating conditions were used to verify the applicability
      of the monitoring system. It was found that the system achieved the goal of
      monitoring during the separation process and realized the function of real-time
      analysis of the received data. The system also gave comprehensible feedback on
      the accidents of material blockages in the feed inlet and high-voltage spark
      discharge. With the warning function of the alarm system, the whole monitoring
      system could save the human cost and help the new technology to be more easily
      applied in industry. 

PMID- 25395160
TI  - Effects of substrate induced respiration on the stability of bottom ash in
      landfill cover environment.
AB  - The municipal solid waste incineration bottom ash is being increasingly used to
      construct landfill covers in Sweden. In post-closure, owing to increased cover
      infiltration, the percolating water can add external organic matter to bottom
      ash. The addition and subsequent degradation of this external organic matter can
      affect metal mobility through complexation and change in redox conditions.
      However, the impacts of such external organic matter addition on bottom ash
      stability have not been fully evaluated yet. Therefore, the objective of this
      study was to evaluate the impact of external organic matter on bottom ash
      respiration and metal leaching. The samples of weathered bottom ash were mixed
      with oven dried and digested wastewater sludge (1%-5% by weight). The aerobic
      respiration activity (AT4), as well as the leaching of metals, was tested with
      the help of respiration and batch leaching tests. The respiration and heavy metal
      leaching increased linearly with the external organic matter addition. Based on
      the results, it was concluded that the external organic matter addition would
      negatively affect the quality of landfill cover drainage. 

PMID- 25395161
TI  - Prevalence of carbapenem-resistant organisms and other Gram-negative MDRO in
      German ICUs: first results from the national nosocomial infection surveillance
      system (KISS).
AB  - PURPOSE: Standardized prevalence and incidence data on carbapenem-resistant
      organisms (CRO) and, as a relevant subgroup, carbapenem-resistant
      Enterobacteriaceae (CRE) are scarce. CRO-surveillance within the German
      nosocomial infection surveillance system (KISS) aims to provide epidemiological
      surveillance data on CRO colonizations and infections. METHODS: CRO-surveillance
      is part of a KISS-module for the surveillance of multidrug-resistant organisms
      (MDRO). MDRO-KISS methods require surveillance of all patients admitted to the
      ward and standardized documentation of imported and ICU-acquired cases. Data on
      all MDRO-carriers including colonization and infection with MDRO are collected.
      All presented data were routine data collected from January 1st 2013 until
      December 1st 2013 in accordance with the German Protection against Infection Act
      (IfSG). RESULTS: 341 ICUs submitted data on MDRO during the first year. In total,
      5,171 cases of multidrug-resistant Gram-negative bacteria (MRGN) were identified.
      848 were CRO (16%). 325 CRO-cases were acquired within the ICU (38%), and 373 CRO
      patients had an infection (44%). CRO-prevalence was 0.29 per 100 patients.
      Acquisition rate of MRGN was 1.32 per 1,000 patient days. This rate is more than
      doubled the acquisition rates of other MDRO under surveillance within MDRO-KISS
      (0.57 MRSA, 0.49 VRE). CRO-acquisition rate was 0.3 per 1,000 patient days.
      Incidence density of MRGN infections bacteria was 0.58 per 1,000 patient days
      (CRO 0.15/1,000 patient days). CONCLUSIONS: To date, CRO are common in German
      ICUs and the relatively large proportions of ICU-acquired CRO and infections
      emphasize their potential to cause outbreaks. High MRGN infection rates and high
      ESBL prevalence data from clinical studies suggest a lack of MRGN identification
      in asymptomatic carriers.

PMID- 25395162
TI  - Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced
      multidrug resistance 1 expression in human A549 lung cancer cells.
AB  - Despite efforts to develop efficient chemotherapeutic drug strategies to treat
      cancer, acquired drug resistance is a commonly encountered problem. In the
      present study, to investigate this phenomenon, human A549 lung cancer cells
      resistant to the topoisomerase inhibitor etoposide (A549RT-eto) were used and
      compared with A549 parental cells. A549RT-eto cells demonstrated increased
      resistance to etoposide-induced apoptosis when compared with A549 parental cells.
      Notably, A549RT-eto cells were observed to exhibit greater levels of histone
      deacetylase 4 (HDAC4), phospho-Stat1 and P-glycoprotein [P-gp; encoded by the
      multidrug resistance 1 (MDR1) gene], compared with A549 cells. To address whether
      HDAC4 protein is involved in etoposide resistance in A549 cells, A549RT-eto cells
      were treated with trichostatin A (TSA; an HDAC inhibitor) during etoposide
      treatment. The combined treatment was demonstrated to enhance etoposide-induced
      apoptosis and reduce expression levels of HDAC4, P-gp and phospho-Stat1. In
      addition, the suppression of Stat1 with siRNA enhanced etoposide-induced
      apoptosis and reduced the expression levels of HDAC4 and P-gp, suggesting that
      Stat1 is essential in the regulation of resistance to etoposide, and in the
      upregulation of P-gp. Notably, TSA treatment reduced P-gp transcript levels but
      Stat1 siRNA treatment did not, suggesting that P-gp is regulated by HDAC at the
      transcriptional level and by Stat1 at the post-transcriptional level. These
      results suggest that the upregulation of Stat1 and HDAC4 determines etoposide
      resistance through P-gp expression in human A549 lung cancer cells.

PMID- 25395163
TI  - HBx transfection limits proliferative capacity of podocytes through cell cycle
      regulation.
AB  - Our previous studies have shown that podocyte number is significantly decreased
      in glomeruli of children with hepatitis B virus (HBV)-associated
      glomerulonephritis. In this study, we aimed to explore whether exogenous
      expression of HBx protein could directly inhibit podocyte proliferation in vitro,
      and to investigate its role in cell cycle regulation. HBx gene was delivered into
      cultured mouse podocytes through an adenovirus-based vector. Cell morphology was
      evaluated with Wright-Giemsa staining. Cell growth and proliferation were
      measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      and 5,6-carboxyfluorescein diacetate, succinimidyl ester (CFSE)-based
      proliferation assays. Cell cycle phase was analyzed by flow cytometry, and the
      expression of cell cycle regulatory proteins was examined by western blot
      analysis. It was found that the aberrant nuclear changes like double and multiple
      micronuclei, which reflect mitotic catastrophe, accumulated in podocytes after 5
      days post-infection. MTT assay showed that Ad.HBx-infected podocytes grew much
      more slowly than controls at day 4 post-infection and thereafter. Furthermore,
      CFSE-based proliferation assay also showed that the proliferation of HBx
      expressing podocytes was significantly inhibited than that of controls at 3-day
      post-infection, and that the difference became much more obvious at day 5 post
      infection. Cell cycle analysis showed that the transfection of HBx resulted in
      significant up-regulation of both cyclin B1 and CDK-inhibitor p21 expression and
      G2/M phase arrest, and slight down-regulation of cyclin A expression. These
      results demonstrated that exogenous expression of HBx might limit the
      proliferative capacity of podocytes through cell cycle regulation, thus
      suggesting that HBx may play a role in podocyte injuries in HBV-associated
      glomerulonephritis. 

PMID- 25395164
TI  - Gold nanomaterials based pseudostationary phases in capillary electrophoresis: a
      brand-new attempt at chondroitin sulfate isomers separation.
AB  - In this work, a CE method with bare gold nanorods (GNRs) based pseudostationary
      phase was developed and applied for the separation of chondroitin sulfate (CS)
      isomers, CS, and dermatan sulfate (DS). The separation efficiency was
      investigated by varying the experimental parameters such as concentration and pH
      of the BGE, separation voltage, internal diameter of capillary, different size,
      and morphology of gold nanomaterials. Results showed that different size and
      morphology of gold nanomaterials had different effects on the separation of CS
      and DS. The best separation of CS and DS was achieved in the BGE composed of
      aqueous 150 mmol/L (mM) ethylenediamine + 20 mM sodium dihydrogen phosphate + 30%
      v/v GNRs, pH 4.5, at the separation voltage of -10 kV. Capillary was 59.2 cm in
      length (effective length 49 cm), 50 MUm id capillary thermostated at 25 degrees
      C. CE with bare GNRs used as pseudostationary phase was shown to be a suitable
      technique for the separation of CS and DS mixtures with wider peaks. RSD of
      migration time and peak area of CS and DS were 0.13, 0.14 and 0.86, 1.07%,
      respectively. 

PMID- 25395165
TI  - Beyond xeroderma pigmentosum: DNA damage and repair in an ecological context. A
      tribute to James E. Cleaver.
AB  - The ability to repair DNA is a ubiquitous characteristic of life on Earth and all
      organisms possess similar mechanisms for dealing with DNA damage, an indication
      of a very early evolutionary origin for repair processes. James E. Cleaver's
      career (initiated in the early 1960s) has been devoted to the study of mammalian
      ultraviolet radiation (UVR) photobiology, specifically the molecular genetics of
      xeroderma pigmentosum and other human diseases caused by defects in DNA damage
      recognition and repair. This work by Jim and others has influenced the study of
      DNA damage and repair in a variety of taxa. Today, the field of DNA repair is
      enhancing our understanding of not only how to treat and prevent human disease,
      but is providing insights on the evolutionary history of life on Earth and how
      natural populations are coping with UVR-induced DNA damage from anthropogenic
      changes in the environment such as ozone depletion. 

PMID- 25395166
TI  - Health surveillance study of workers who manufacture multi-walled carbon
      nanotubes.
AB  - While many in vivo and in vitro toxicology studies of multi-walled carbon
      nanotubes (MWCNTs) have already indicated that exposure to MWCNTs can potentially
      induce health effects in humans, the actual health effects of MWCNTs among
      exposed workers are not yet known. Moreover, the levels of exposure and internal
      doses of MWCNTs are becoming more and more important for estimating the health
      effects resulting from exposure to MWCNTs. However, information on biomonitoring
      and exposure to MWCNTs remains limited. Therefore, the authors conducted a health
      surveillance study in a workplace that manufactures MWCNTs, including assessment
      of the personal and area exposure levels to MWCNTs, a walk-through evaluation of
      the manufacturing process, and collection of blood and exhaled breath condensates
      (EBCs) from the MWCNT manufacturing and office workers. In addition, a pulmonary
      function test was also conducted on the MWCNT manufacturing workers (9) and
      office workers (4). The worker exposure to elemental carbon was found to be 6.2
      9.3 MUg/m(3) in the personal samplings and 5.5-7.3 MUg/m(3) in the area
      samplings. Notwithstanding, the workers exhibited a normal range of hematology
      and blood biochemistry values and normal lung function parameters. When analyzing
      the EBCs, the malondialdehyde (MDA), 4-hydroxy-2-hexenal (4-HHE) and n-hexanal
      levels in the MWCNT manufacturing workers were significantly higher than those in
      the office workers. The MDA and n-hexanal levels were also significantly
      correlated with the blood molybdenum concentration, suggesting MDA, n-hexanal and
      molybdenum as useful biomarkers of MWCNT exposure. 

PMID- 25395167
TI  - Fibrinogen enhances the inflammatory response of alveolar macrophages to TiO2,
      SiO2 and carbon nanomaterials.
AB  - Many studies have shown that the composition of the protein corona dramatically
      affects the response of cells to nanomaterials (NMs). However, the role of each
      single protein is still largely unknown. Fibrinogen (FG), one of the most
      abundant plasma proteins, is believed to mediate foreign-body reactions. Since
      this protein is absent in cell media used in in vitro toxicological tests the
      possible FG-mediated effects have not yet been assessed. Here, the effect of FG
      on the toxicity of three different kinds of inorganic NMs (carbon, SiO2 and TiO2)
      on alveolar macrophages has been investigated. A set of integrated techniques (UV
      vis spectroscopy, dynamic light scattering and sodium dodecyl sulphate
      polyacrylamide gel electrophoresis) have been used to study the strength and the
      kinetics of interaction of FG with the NMs. The inflammatory response of alveolar
      macrophages (MH-S) exposed to the three NMs associated with FG has also been
      investigated. We found that FG significantly enhances the cytotoxicity (lactate
      dehydrogenase leakage) and the inflammatory response (increase in nitric oxide
      (NO) concentration and NO synthase activation) induced by SiO2, carbon and TiO2
      NMs on alveolar macrophages. This effect appears related to the amount of FG
      interacting with the NMs. In the case of carbon NMs, the activation of
      fibrinolysis, likely related to the exposure of cryptic sites of FG, was also
      observed after 24 h. These findings underline the critical role played by FG in
      the toxic response to NMs. 

PMID- 25395168
TI  - Extracellular ATP: a potential regulator of plant cell death.
AB  - Adenosine 5'-triphosphate (ATP) has been regarded as an intracellular energy
      currency molecule for many years. In recent decades, it has been determined that
      ATP is released into the extracellular milieu by animal, plant and microbial
      cells. In animal cells, this extracellular ATP (eATP) functions as a signalling
      compound to mediate many cellular processes through its interaction with membrane
      associated receptor proteins. It has also been reported that eATP is a signalling
      molecule required for the regulation of plant growth, development and responses
      to environmental stimuli. Recently, the first plant receptor for eATP was
      identified in Arabidopsis thaliana. Interestingly, some studies have shown that
      eATP is of particular importance in the control of plant cell death. In this
      review article, we summarize and discuss the theoretical and experimental
      advances that have been made with regard to the roles and mechanisms of eATP in
      plant cell death. We also make an attempt to address some speculative aspects to
      help develop and expand future research in this area. 

PMID- 25395169
TI  - Specific deficiency of Plzf paralog, Zbtb20, in Sertoli cells does not affect
      spermatogenesis and fertility in mice.
AB  - Ztbt20 is a POK family transcription factor and primarily functions through its
      conserved C2H2 Kruppel type zinc finger and BTB/POZ domains. The present study
      was designed to define the function of the Zbtb20, in vivo, during mouse
      spermatogenesis. Immunohistochemical studies revealed that ZBTB20 protein was
      localized specifically in the nuclei of Sertoli cells in seminiferous tubules. To
      investigate its role during spermatogenesis, we crossed Amh-Cre transgenic mice
      with Zbtb20 floxp mice to generate conditionally knockout mice (cKO) in which
      Zbtb20 was specifically deleted in Sertoli cells. The cKO mice were fertile and
      did not show any detectable abnormalities in spermatogenesis. Taken together,
      though specific deletion of transcription factor Zbtb20 in Sertoli cells has no
      apparent influence on spermatogenesis, its specific localization in Sertoli cells
      makes Zbtb20 a useful marker for the identification of Sertoli cells in
      seminiferous tubules. 

PMID- 25395171
TI  - Celebrating Robin Room.

PMID- 25395172
TI  - Robin Room and cannabis policy: dangerous comparisons.
AB  - This paper describes Robin Room's contribution to cannabis policy debates over
      the period 1993-2010. It focuses on a controversy that erupted over a review that
      Room and the author undertook for the World Health Organization in the mid-1990s
      on the comparative harms of cannabis, alcohol, opiates and tobacco. It also
      briefly describes Room's recent work on global cannabis policy and ends with a
      brief appreciation of the character of his scholarly contributions to this field.

PMID- 25395170
TI  - CSN6 drives carcinogenesis by positively regulating Myc stability.
AB  - Cullin-RING ubiquitin ligases (CRLs) are critical in ubiquitinating Myc, while
      COP9 signalosome (CSN) controls neddylation of Cullin in CRL. The mechanistic
      link between Cullin neddylation and Myc ubiquitination/degradation is unclear.
      Here we show that Myc is a target of the CSN subunit 6 (CSN6)-Cullin signalling
      axis and that CSN6 is a positive regulator of Myc. CSN6 enhanced neddylation of
      Cullin-1 and facilitated autoubiquitination/degradation of Fbxw7, a component of
      CRL involved in Myc ubiquitination, thereby stabilizing Myc. Csn6 haplo
      insufficiency decreased Cullin-1 neddylation but increased Fbxw7 stability to
      compromise Myc stability and activity in an EMU-Myc mouse model, resulting in
      decelerated lymphomagenesis. We found that CSN6 overexpression, which leads to
      aberrant expression of Myc target genes, is frequent in human cancers. Together,
      these results define a mechanism for the regulation of Myc stability through the
      CSN-Cullin-Fbxw7 axis and provide insights into the correlation of CSN6
      overexpression with Myc stabilization/activation during tumorigenesis. 

PMID- 25395173
TI  - Composite peptide-based vaccines for cancer immunotherapy (Review).
AB  - The use of peptide-based vaccines as therapeutics aims to elicit immune responses
      through antigenic epitopes derived from tumor antigens. Peptide-based vaccines
      are easily synthesized and chemically stable entities, and of note, they are
      absent of oncogenic potential. However, their application is more complicated as
      the success of an effective peptide-based vaccine is determined by numerous
      parameters. The success thus far has been limited by the choice of tumor
      antigenic peptides, poor immunogenicity and incorporation of strategies to
      reverse cancer-mediated immune suppression. In the present review, an overview of
      the mechanisms of peptide-based vaccines is provided and antigenic peptides are
      categorized with respect to their tissue distribution in order to determine their
      usefulness as targets. Furthermore, certain approaches are proposed that induce
      and maintain T cells for immunotherapy. The recent progress indicates that
      peptide-based vaccines are preferential for targeted therapy in cancer patients.

PMID- 25395174
TI  - Let There Be Light! Bioluminescent Imaging to Study Bacterial Pathogenesis in
      Live Animals and Plants.
AB  - : Bioluminescence imaging (BLI) of bacteria was primarily designed to permit real
      time, sensitive, and noninvasive monitoring of the progression of infection in
      live animals. Generally, BLI relies on the construction of bacterial strains that
      possess the lux operon. The lux operon is composed of a set of genes that encode
      the luciferase enzyme and its cognate substrate, which interact to produce light
      a phenomenon that is referred to as bioluminescence. Bioluminescence emitted by
      the bacteria can then be detected and imaged within a living host using sensitive
      charge-coupled device (CCD) cameras. In comparison to traditional host-pathogen
      studies, BLI offers the opportunity for extended monitoring of infected animals
      without resorting to euthanasia and extensive tissue processing at each time
      point. Therefore, BLI can reduce the number of animals required to generate
      meaningful data, while significantly contributing to the understanding of
      pathogenesis in the host and, subsequently, the development and evaluation of
      adequate vaccines and therapeutics. BLI is also useful in characterizing the
      interactions of pathogens with plants and the para-host environment. In this
      chapter, we demonstrate the broad application of BLI for studying bacterial
      pathogens in different niches. Furthermore, we will specifically focus on the use
      of BLI to characterize the following: (1) the pathogenesis of Brucella melitensis
      in mice (animal host), and (2) the progression of infection of Clavibacter
      michiganensis subsp. michiganensis in tomatoes (plant host). These studies will
      provide an overview of the wide potential of BLI and its role in enhancing the
      study of unique-and sometimes difficult-to-characterize-bacterial pathogens.

PMID- 25395175
TI  - Heuristic identification of biological architectures for simulating complex
      hierarchical genetic interactions.
AB  - Simulation plays an essential role in the development of new computational and
      statistical methods for the genetic analysis of complex traits. Most simulations
      start with a statistical model using methods such as linear or logistic
      regression that specify the relationship between genotype and phenotype. This is
      appealing due to its simplicity and because these statistical methods are
      commonly used in genetic analysis. It is our working hypothesis that simulations
      need to move beyond simple statistical models to more realistically represent the
      biological complexity of genetic architecture. The goal of the present study was
      to develop a prototype genotype-phenotype simulation method and software that are
      capable of simulating complex genetic effects within the context of a
      hierarchical biology-based framework. Specifically, our goal is to simulate
      multilocus epistasis or gene-gene interaction where the genetic variants are
      organized within the framework of one or more genes, their regulatory regions and
      other regulatory loci. We introduce here the Heuristic Identification of
      Biological Architectures for simulating Complex Hierarchical Interactions
      (HIBACHI) method and prototype software for simulating data in this manner. This
      approach combines a biological hierarchy, a flexible mathematical framework, a
      liability threshold model for defining disease endpoints, and a heuristic search
      strategy for identifying high-order epistatic models of disease susceptibility.
      We provide several simulation examples using genetic models exhibiting
      independent main effects and three-way epistatic effects. 

PMID- 25395176
TI  - Outcomes following resection of intrahepatic cholangiocarcinoma.
AB  - OBJECTIVES: The aim of this analysis was to examine prognostic features and
      outcomes in patients undergoing resection for intrahepatic cholangiocarcinoma
      (ICC). METHODS: A retrospective chart review was performed in all patients who
      underwent R0 or R1 resection for primary ICC between 1995 and 2011. Clinical data
      were abstracted and statistical analyses were conducted in the standard fashion.
      RESULTS: A total of 82 patients underwent curative hepatectomy for primary ICC;
      51 patients in this cohort developed recurrence. The median follow-up of
      survivors was 27 months (range: 1-116 months). Recurrences were intrahepatic
      (65%), associated with multiple tumours (54%) and occurred during the first 2
      years after hepatectomy (86%). The main factor associated with recurrence after
      resection was the presence of satellite lesions. Overall 5-year disease-free
      survival after primary resection was 16%. Factors associated with poor survival
      were transfusion and perineural invasion. Treatment of recurrence was undertaken
      in 89% of patients and repeat surgical resection was performed in 15 patients.
      The 3-year survival rate after recurrence was 25%. Prolonged survival after
      recurrence was associated with a solitary tumour recurrence. CONCLUSIONS: Despite
      curative resection of ICC, recurrence can be expected to occur in 79% of patients
      at 5 years. Predictors of survival and recurrence after resection vary in the
      literature. In patients with recurrence, selection of the optimal treatment
      remains challenging.

PMID- 25395177
TI  - Trends in Kaposi's sarcoma-associated Herpesvirus antibodies prior to the
      development of HIV-associated Kaposi's sarcoma: a nested case-control study.
AB  - HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan
      Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus
      (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control
      study within a long-standing clinical cohort in rural Uganda, we used stored sera
      to examine the evolution of antibody titres against the KSHV antigens K8.1 and
      latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who
      subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV
      coinfected controls who did not develop KS. Throughout the 6 years prior to
      diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases
      than controls (p < 0.0001), and titres increased prior to diagnosis in the cases.
      K8.1 titres differed more between KS cases and controls, compared to LANA titres.
      These differences in titre between cases and controls suggest a role for lytic
      viral replication in the pathogenesis of HIV-related KS in this setting.

PMID- 25395178
TI  - Morphokinetic analysis of cleavage stage embryos and its relationship to
      aneuploidy in a retrospective time-lapse imaging study.
AB  - PURPOSE: To analyze differences in morphokinetic parameters of chromosomally
      normal and aneuploid embryos utilizing time-lapse imaging and CGH microarray
      analysis. METHODS: This retrospective cohort study included patients undergoing
      IVF treatment and preimplantation genetic diagnosis for sex selection. A total of
      460 embryos cultured in incubators with time-lapse imaging system (EmbryoScope)
      were selected for biopsy on day 3 of development. Subsequently, CGH microarray
      analysis was performed for aneuploidy screening of 24 chromosomes. Kinetic
      parameters including time for appearance of second polar body (tPB2), time of
      pronuclei appearance (tPNa), time of pronuclei fading (tPBf), time to division to
      2(t2), 3(t3), 4(t4), 5(t5) cells, length of second and third cell cycle (CC2= t3
      t2, CC3=t5-t3), synchrony of cell division from 2 to 4 cells (S2=t4-t3) and
      interval t5-t2 were analyzed to compare chromosomally normal and abnormal
      embryos. RESULTS: The mean time durations for tPNf, t2, t5, CC2, CC3, t5-t2
      differed significantly between normal and abnormal embryos. CONCLUSIONS: Time
      lapse imaging morphokinetics may play a role in early prediction of aneuploid
      embryos due to differences in kinetic behavior that may aid in improving clinical
      outcome.

PMID- 25395179
TI  - Understanding reproducibility of human IVF traits to predict next IVF cycle
      outcome; common mistake.

PMID- 25395180
TI  - Spatially embedded growing small-world networks.
AB  - Networks in nature are often formed within a spatial domain in a dynamical
      manner, gaining links and nodes as they develop over time. Motivated by the
      growth and development of neuronal networks, we propose a class of spatially
      based growing network models and investigate the resulting statistical network
      properties as a function of the dimension and topology of the space in which the
      networks are embedded. In particular, we consider two models in which nodes are
      placed one by one in random locations in space, with each such placement followed
      by configuration relaxation toward uniform node density, and connection of the
      new node with spatially nearby nodes. We find that such growth processes
      naturally result in networks with small-world features, including a short
      characteristic path length and nonzero clustering. We find no qualitative
      differences in these properties for two different topologies, and we suggest that
      results for these properties may not depend strongly on the topology of the
      embedding space. The results do depend strongly on dimension, and higher
      dimensional spaces result in shorter path lengths but less clustering. 

PMID- 25395181
TI  - Nedd4-1 is an exceptional prognostic biomarker for gastric cardia adenocarcinoma
      and functionally associated with metastasis.
AB  - BACKGROUND: Gastric cardia adenocarcinoma (GCA) is the most aggressive subtype of
      gastric carcinoma. New molecular markers and therapeutic targets are needed for
      diagnosis, prognosis and treatment of GCA. This study is to establish the E3
      ubiquitin ligase Nedd4-1 as a prognostic biomarker to predict the survival and
      guide the treatment of GCA patients. METHODS: Expression of Nedd4-1 in 214 GCA
      tumor samples was detected by immunohistochemistry staining (IHC) using tissue
      microarray assay (TMA). Association of Nedd4-1 with cumulative survival of the
      TNM stages I-III patients and clinicopathological characteristics was
      statistically analyzed. The role of Nedd4-1 in gastric cancer cell migration and
      invasion were determined by transwell and wound healing assays. RESULTS: Nedd4-1
      is overexpressed in 83% of the GCA tumors. The 5-year survival rate in Nedd4-1
      negative GCA patients is as high as 96%. Log-rank analysis indicated that
      overexpression of Nedd4-1 is inversely correlated with cumulative survival
      (chi(2) = 21.885, p <0.001). Multivariate logistic regression analysis showed
      that overexpression of Nedd4-1 is associated with an extremely low GCA survival
      rate with a hazard ratio (HR) = 0.068 (p = 0.008) in TNM stages I-III patients.
      Statistical analysis of association of Nedd4-1 overexpression with
      clinicopathological characteristics revealed that overexpression of Nedd4-1 is
      tightly associated with TNM stage (p < 0.001). Knockdown of Nedd4-1 in gastric
      cancer cell lines AGS and N87 dramatically inhibited the gastric cancer cell
      migration and invasion. CONCLUSIONS: Our results indicate that Nedd4-1 is an
      exceptional prognostic biomarker for GCA and suggest that Nedd4-1 may play an
      essential role in GCA metastasis.

PMID- 25395182
TI  - Pre-treatment with a Xingnaojing preparation ameliorates sevoflurane-induced
      neuroapoptosis in the infant rat striatum.
AB  - Xingnaojing (XNJ), is a standardized Chinese herbal medicine product derived from
      An Gong Niu Huang Pill. It may be involved in neuroprotection in a number of
      neurological disorders. Exposure to anesthetic agents during the brain growth
      spurt may trigger widespread neuroapoptosis in the developing brain. Thus the
      present study aimed to identify whether there was a neuroprotective effect of XNJ
      on anesthesia-induced neuroapoptosis. Seven-day-old rats received treatment with
      2.1% sevoflurane for 6 h. Rat pups were injected intraperitoneally with 1 or 10
      ml/kg XNJ at 0.2, 24 and 48 h prior to sevoflurane exposure. The striata of
      neonatal rats were collected following administration of anesthesia. Western
      blotting and immunohistochemistry were used to analyze the expression of
      activated caspase 3, Bax and phosphorylated protein kinase B (p-AKT) in the
      striatum. It was found that activated caspase 3 and Bax expression were
      upregulated in the striatum following sevoflurane treatment. Preconditioning with
      XNJ attenuated the neuronal apoptosis induced by sevoflurane in a dose-dependent
      manner. Anesthesia reduced the expression of p-AKT (phosphorylated at sites
      Thr308 and Ser473) and phosphorylated extracellular-regulated protein kinase (p
      ERK) in the striatum. Pre-treatment with XNJ reversed the reduction in p-AKT, but
      not p-ERK expression. These data suggest that XNJ has an antiapoptotic effect
      against sevoflurane-induced cell loss in the striatum. It thus holds promise as a
      safe and effective neuroprotective agent. The action of XNJ on p-AKT may make a
      significant contribution to its neuroprotective effect.

PMID- 25395184
TI  - Vertical gradients in regional alveolar oxygen tension in supine human lung
      imaged by hyperpolarized 3He MRI.
AB  - The purpose of this study was to evaluate whether regional alveolar oxygen
      tension (P(A)O2) vertical gradients imaged with hyperpolarized (3)He can identify
      smoking-induced pulmonary alterations. These gradients are compared with common
      clinical measurements including pulmonary function tests (PFTs), the six minute
      walk test, and the St. George's Respiratory Questionnaire. 8 healthy non-smokers,
      12 asymptomatic smokers, and 7 symptomatic subjects with chronic obstructive
      pulmonary disease (COPD) underwent two sets of back-to-back P(A)O2 imaging
      acquisitions in the supine position in two opposite directions (top to bottom and
      bottom to top), followed by clinically standard pulmonary tests. The whole-lung
      mean, standard deviation (DP(A)O2) and vertical gradients of P(A)O2 along the
      slices were extracted, and the results were compared with clinically derived
      metrics. Statistical tests were performed to analyze the differences between
      cohorts. The anterior-posterior vertical gradients and DP(A)O2 effectively
      differentiated all three cohorts (p < 0.05). The average vertical gradient P(A)O2
      in healthy subjects was -1.03 +/- 0.51 Torr/cm toward lower values in the
      posterior/dependent regions. The directional gradient was absent in smokers (0.36
      +/- 1.22 Torr/cm) and was in the opposite direction in COPD subjects (2.18 +/-
      1.54 Torr/cm). The vertical gradients correlated with smoking history (p =
      0.004); body mass index (p = 0.037), PFT metrics (forced expiratory volume in 1
      s, p = 0.025; residual volume/total lung capacity percent predicted, p = 0.033)
      and with distance walked in 6 min (p = 0.009). Regional P(A)O2 data indicate that
      cigarette smoke induces physiological alterations that are not being detected by
      the most widely used physiological tests.

PMID- 25395186
TI  - Stimulating Evidence for Pneumococcal Conjugate Vaccination Among HIV-Infected
      Adults.

PMID- 25395183
TI  - Heterogeneity and individuality: microRNAs in mental disorders.
AB  - MicroRNAs are about 22 nucleotide long single-stranded RNA molecules, negatively
      regulating gene expression of a single gene or a gene network. In neural tissues,
      they have been implicated in developmental and neuroplasticity-related processes,
      such as neurogenesis, differentiation, apoptosis and long-term potentiation.
      Their molecular mode of action is reminiscent of findings of genome-wide
      association studies in mental disorders, unable to attribute the risk of disease
      to a specific gene, but rather to multiple genes, gene-networks and gene
      environment interaction. As such, microRNAs are an attractive target for
      research. Here, we review clinical studies conducted in humans on microRNAs in
      mental disorders with a particular focus on schizophrenia, bipolar disorder,
      major depressive disorder and anxiety disorders. The majority of clinical studies
      have focused on schizophrenia. The most robust finding has been reported for
      rs1625579 located in MIR137HG, which was associated with schizophrenia on a
      genome-wide level. Concerning bipolar disorder, major depression and anxiety
      disorders, promising results have been published, but only a considerably smaller
      number of clinical studies is available and genome-wide association studies did
      not suggest a direct link to microRNAs so far. Expression of microRNAs as
      biomarkers of mental disorders and treatment response is currently emerging with
      preliminary results. Larger-scaled genetic and functional studies along with
      translational research are needed to enhance our understanding of microRNAs in
      mental disorders. These studies will aid in disentangling the complex genetic
      nature of these disorders and possibly contribute to the development of novel,
      individualized diagnostic and therapeutic approaches. 

PMID- 25395187
TI  - Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine in HIV
      Infected Adults Previously Vaccinated With Pneumococcal Polysaccharide Vaccine.
AB  - BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at
      increased risk of pneumococcal disease. We evaluated the safety and
      immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) in this
      population. METHODS: HIV-infected persons >= 18 years of age who were previously
      vaccinated with >= 1 dose of 23-valent pneumococcal polysaccharide vaccine
      (PPSV23) and had CD4 cell counts >= 200 cells/mm(3) and HIV viral loads <50 000
      copies/mL were enrolled in this 3-dose PCV13 open-label study. RESULTS: A total
      of 329 subjects received >= 1 dose, and 279 received 3 doses administered at 6
      month intervals. Increases in anticapsular polysaccharide immunoglobulin G
      concentrations and opsonophagocytic antibody titers were demonstrated 1 month
      after each of the 3 doses of PCV13. Antibody levels were generally similar after
      each dose. The responses were similar whether subjects had previously received 1
      or >= 2 doses of PPSV23. Pain at the injection-site was the most common local
      reaction. Severe injection site or systemic events were uncommon. CONCLUSIONS:
      Vaccination with PCV13 induces anticapsular immunoglobulin G and opsonophagocytic
      antibody responses in HIV-infected adults with prior PPSV23 vaccination and CD4
      cell counts >= 200 cells/mm(3). The observations support the use of PCV13 in this
      population. CLINICAL TRIALS REGISTRATION: NCT00963235.

PMID- 25395188
TI  - Simultaneous determination of florfenicol with its metabolite based on modified
      quick, easy, cheap, effective, rugged, and safe sample pretreatment and
      evaluation of their degradation behavior in agricultural soils.
AB  - A simple and simultaneous method for the determination of florfenicol and its
      metabolite florfenicol amine in agricultural soils using modified quick, easy,
      cheap, effective, rugged, and safe sample pretreatment and reversed-phase high
      performance liquid chromatography with tandem mass spectrometry is presented.
      Florfenicol and its metabolite florfenicol amine residues in agricultural soils
      were extracted with alkalized acetonitrile and an aliquot was cleaned up with
      Si(CH2)3NH(CH2)2NH2 and C18 sorbent, which were powder materials. High
      performance liquid chromatography with tandem mass spectrometry was applied to
      simultaneously determine the level of florfenicol and florfenicol amine in
      agricultural soils. Excellent linearity was achieved for florfenicol and
      florfenicol amine over a range of concentrations from 0.1-500 MUg/L with
      coefficients more than 0.99. Average recoveries at four different levels (0.005,
      0.05, 0.5, and 5.0 mg/kg) for florfenicol and florfenicol amine ranged from 73.6
      94.9% with relative standard deviations of 2.9-12.5%. The limits of detection for
      florfenicol and florfenicol amine in agricultural soils were 2.0 MUg/kg, and the
      limits of quantification were 6.0 MUg/kg. Based on this method, the degradation
      behavior of florfenicol and its metabolite florfenicol amine in three soils
      (Nanchang, Hangzhou, and Changchun) under sterilized and native conditions was
      investigated and the transformation rate of florfenicol amine from florfenicol
      was evaluated.

PMID- 25395189
TI  - Surgical correction of an aortico-left ventricular tunnel originating from the
      left aortic sinus with a left coronary artery anomaly.
AB  - Aortico-left ventricular tunnel (ALVT) is an unusual congenital anomalous
      communication between the aorta and the left ventricle. We present an ALVT
      arising from the left aortic sinus that was repaired surgically.

PMID- 25395190
TI  - Prototyping of wrinkled nano-/microstructured electrodes for electrochemical DNA
      detection.
AB  - Biosensing platforms are ideal for addressing the diagnostic needs of resource
      poor areas; however, the translation of such systems from the laboratory to the
      point-of-need has been a slow process. Rapid prototyping methods that enable an
      application-specific biosensor to be created in a matter of hours from design to
      fabrication would expedite the clinical and field testing of such systems. Here,
      we demonstrate a benchtop method based on craft cutting and polymer-induced
      wrinkling for creating multiplexed electrochemical DNA biosensors. This
      fabrication method allows multiscale wrinkled electrodes with features in the
      millimeter to nanometer length scales to be created in a matter of hours. These
      wrinkled electrodes display an enhanced surface area compared to planar
      electrodes and are shown to be structurally tunable by changing the film
      thickness. We demonstrate that structural tunability of these electrodes is
      translatable to functional tunability as the density of surface-immobilized probe
      molecules can be manipulated using wrinkled electrodes of different thicknesses.
      Furthermore, a simple proof-of-concept electrocatalytic DNA biosensor is
      demonstrated for distinguishing between complementary and noncomplementary
      oligonucleotides. 

PMID- 25395191
TI  - Zolmitriptan inhibits neurogenic inflammation and pain during electrical
      stimulation in human skin.
AB  - BACKGROUND: Triptans are agonists to 5-HT 1B/D/F receptors, which are present on
      nociceptive neurons not only within but also beyond the trigeminal system. The
      aim of this study was to investigate whether zolmitriptan interacts with
      peptidergic nociceptive afferents in human skin. METHODS: Twenty participants (13
      women, median age: 25; interquartile range: 23-26 years) entered the randomized,
      double-blind, cross-over study. Electrically induced neurogenic flare and pain
      was assessed after either placebo or zolmitriptan on the ventral thigh.
      Mechanical pain thresholds were investigated at baseline and after electrical
      stimulation at the stimulation site. RESULTS: The size of the neurogenic flare (F
      = 10.9; p = 0.002) as well as electrically induced pain were significantly
      reduced by zolmitriptan (F = 4.46; p = 0.041). Moreover, electrically induced
      pinprick hyperalgesia was significantly decreased by zolmitriptan compared with
      placebo (F = 6.243; p = 0.017). CONCLUSIONS: Triptans may have effects outside of
      the trigeminal system and reduce electrically evoked neurogenic inflammation and
      pain in human skin.

PMID- 25395192
TI  - Evaluation of the protective effect of silibinin in rats with liver damage caused
      by itraconazole.
AB  - Itraconazole (ITZ) belongs to the triazole group of antifungals with potent
      keratinophilic and lipophilic features. Hepatotoxicity is one of its most
      remarkable features. Silibinin (SIL) is a plant used worldwide which is used in
      the treatment of many liver diseases and it is especially very well known for its
      hepatoprotective-cytoprotective effect. The aim of our study was to research the
      protective effect of SIL in ITZ-induced hepatotoxicity using biochemical and
      pathological tests. Liver enzymes and antioxidant enzyme activities were measured
      spectrophotometrically by using commercial kits. ALT and AST levels in ITZ group
      were significantly increased compared to the group, while the activities of GSH
      Px and SOD had decreased (p < 0.05). When ITZ group was compared to ITZ + SIL
      group, AST, ALT, and levels of NO and MPO were significantly decreased, while the
      activities of GSH-Px and SOD were increased (p < 0.05). Histopathological
      evaluation showed that SIL significantly decreased periportal inflammation and
      parenchymal hepatocyte apoptosis in ITZ and ITZ + SIL groups (p < 0.05).
      Eventhough not statistically significant, partial improvement with the use of SIL
      has been detected (p > 0.05) in hepatocyte degeneration and multinuclear giant
      cell formation. According to the evaluation performed with comet assay method,
      ITZ leads to DNA damage, and the use of SIL significantly decreases DNA damage (p
      < 0.05). We have detected that the use of ITZ increases oxidative stress (MPO,
      NO), decreases antioxidant activity (SOD and GSH-Px), and leads to DNA damage and
      histopathological liver damage, whereas the use of SIL has a cytoprotective
      effect on the liver by increasing the antioxidant effect (SOD, GSH-Px) and by
      decreasing the oxidative stress (NO, MPO). ITZ causes the generation of ROS and
      leads to DNA damage and liver damage. SIL has a cytoprotective effect on the
      liver by increasing antioxidant enzyme activities, preventing the formation of
      ROS. 

PMID- 25395193
TI  - The Quantitative Ideas and Methods in Assessment of Four Properties of Chinese
      Medicinal Herbs.
AB  - The purpose of this review is to summarize and reflect on the current status and
      problems of the research on the properties of Chinese medicinal herbs. Hot, warm,
      cold, and cool are the four properties/natures of Chinese medicinal herbs. They
      are defined based on the interaction between the herbs with human body. How to
      quantitatively assess the therapeutic effect of Chinese medicinal herbs based on
      the theoretical system of Traditional Chinese medicine (TCM) remains to be a
      challenge. Previous studies on the topic from several perspectives have been
      presented. Results and problems were discussed. New ideas based on the technology
      of biophoton radiation detection are proposed. With the development of biophoton
      detection technology, detection and characterization of human biophoton emission
      has led to its potential applications in TCM. The possibility of using the
      biophoton analysis system to study the interaction of Chinese medicinal herbs
      with human body and to quantitatively determine the effect of the Chinese
      medicinal herbal is entirely consistent with the holistic concept of TCM theory.
      The statistical entropy of electromagnetic radiations from the biological systems
      can characterize the four properties of Chinese medicinal herbs, and the spectrum
      can characterize the meridian tropism of it. Therefore, we hypothesize that by
      the use of biophoton analysis system, the four properties and meridian tropism of
      Chinese medicinal herbs can be quantitatively expressed. 

PMID- 25395194
TI  - The Effect of EPO Gene Overexpression on Proliferation and Migration of Mouse
      Bone Marrow-Derived Mesenchymal Stem Cells.
AB  - The aim of this study is to investigate the effect of erythropoietin (EPO) gene
      overexpression on proliferation and migration of mouse bone marrow-derived
      mesenchymal stem cells (MSCs), and to determine the underlying signaling pathway.
      Mouse MSCs were cultured in vitro and EPO gene was transfected into the 6th
      generation of MSCs via lentivirus vector. The transfected cells were identified
      by flow cytometry and the EPO levels in supernatant were measured with ELISA. In
      addition, cell proliferation was assessed by CCK-8 assay and cell migration was
      evaluated by Transwell assay. The activation of Akt, ERK1/2, and p38MAPK
      signaling was detected by western blotting. The lentivirus vector containing EPO
      was successfully constructed and transfected into MSCs. No remarkable change was
      found in the cell surface markers after transfection while a significant increase
      of EPO level in supernatant was noticed in transfected MSCs compared to controls
      (P < 0.01). In addition, transfected MSCs showed a significantly enhanced
      proliferation (P < 0.01) as well as a notable increase in migration (P < 0.01)
      compared to controls. Furthermore, we also found that EPO modification enhanced
      the phosphorylation of PI3K/Akt and ERK signaling pathway, and suppressed the
      phosphorylation of p38MAPK without affecting the levels of total Akt, ERK1/2, and
      p38MAPK in MSCs. After transfection, MSCs secreted more EPO which enhanced the
      capability of proliferation and migration. Moreover, our results suggested that
      the enhanced proliferation and migration might be associated with activation of
      PI3K/Akt and ERK or inhibition of P38MAPK signaling pathway.

PMID- 25395195
TI  - Exploring the Genomic Roadmap and Molecular Phylogenetics Associated with MODY
      Cascades Using Computational Biology.
AB  - Maturity onset diabetes of the young (MODY) is a metabolic and genetic disorder.
      It is different from type 1 and type 2 diabetes with low occurrence level (1-2%)
      among all diabetes. This disorder is a consequence of beta-cell dysfunction. Till
      date, 11 subtypes of MODY have been identified, and all of them can cause gene
      mutations. However, very little is known about the gene mapping, molecular
      phylogenetics, and co-expression among MODY genes and networking between
      cascades. This study has used latest servers and software such as VarioWatch,
      ClustalW, MUSCLE, G Blocks, Phylogeny.fr, iTOL, WebLogo, STRING, and KEGG PATHWAY
      to perform comprehensive analyses of gene mapping, multiple sequences alignment,
      molecular phylogenetics, protein-protein network design, co-expression analysis
      of MODY genes, and pathway development. The MODY genes are located in chromosomes
      2, 7, 8, 9, 11, 12, 13, 17, and 20. Highly aligned block shows Pro, Gly, Leu,
      Arg, and Pro residues are highly aligned in the positions of 296, 386, 437, 455,
      456 and 598, respectively. Alignment scores inform us that HNF1A and HNF1B
      proteins have shown high sequence similarity among MODY proteins. Protein-protein
      network design shows that HNF1A, HNF1B, HNF4A, NEUROD1, PDX1, PAX4, INS, and GCK
      are strongly connected, and the co-expression analyses between MODY genes also
      show distinct association between HNF1A and HNF4A genes. This study has used
      latest tools of bioinformatics to develop a rapid method to assess the
      evolutionary relationship, the network development, and the associations among
      eleven MODY genes and cascades. The prediction of sequence conservation,
      molecular phylogenetics, protein-protein network and the association between the
      MODY cascades enhances opportunities to get more insights into the less-known
      MODY disease.

PMID- 25395197
TI  - Structural Rearrangements in CHO Cells After Disruption of Individual
      Cytoskeletal Elements and Plasma Membrane.
AB  - Cellular structural integrity is provided primarily by the cytoskeleton, which
      comprises microtubules, actin filaments, and intermediate filaments. The plasma
      membrane has been also recognized as a mediator of physical forces, yet its
      contribution to the structural integrity of the cell as a whole is less clear. In
      order to investigate the relationship between the plasma membrane and the
      cytoskeleton, we selectively disrupted the plasma membrane and each of the
      cytoskeletal elements in Chinese hamster ovary cells and assessed subsequent
      changes in cellular structural integrity. Confocal microscopy was used to
      visualize cytoskeletal rearrangements, and optical tweezers were utilized to
      quantify membrane tether extraction. We found that cholesterol depletion from the
      plasma membrane resulted in rearrangements of all cytoskeletal elements.
      Conversely, the state of the plasma membrane, as assessed by tether extraction,
      was affected by disruption of any of the cytoskeletal elements, including
      microtubules and intermediate filaments, which are located mainly in the cell
      interior. The results demonstrate that, besides the cytoskeleton, the plasma
      membrane is an important contributor to cellular integrity, possibly by acting as
      an essential framework for cytoskeletal anchoring. In agreement with the
      tensegrity model of cell mechanics, our results support the notion of the cell as
      a prestressed structure. 

PMID- 25395196
TI  - Acrolein-Induced Oxidative Stress and Cell Death Exhibiting Features of Apoptosis
      in the Yeast Saccharomyces cerevisiae Deficient in SOD1.
AB  - The yeast Saccharomyces cerevisiae is a useful eukaryotic model to study the
      toxicity of acrolein, an important environmental toxin and endogenous product of
      lipid peroxidation. The study was aimed at elucidation of the cytotoxic effect of
      acrolein on the yeast deficient in SOD1, Cu, Zn-superoxide dismutase which is
      hypersensitive to aldehydes. Acrolein generated within the cell from its
      precursor allyl alcohol caused growth arrest and cell death of the yeast cells.
      The growth inhibition involved an increase in production of reactive oxygen
      species and high level of protein carbonylation. DNA condensation and
      fragmentation, exposition of phosphatidylserine at the cell surface as well as
      decreased dynamic of actin microfilaments and mitochondria disintegration point
      to the induction of apoptotic-type cell death besides necrotic cell death. 

PMID- 25395198
TI  - Cerium Oxide Nanoparticles Induce Oxidative Stress and Genotoxicity in Human Skin
      Melanoma Cells.
AB  - Extensive applications of cerium oxide (CeO2) nanoparticles require a better
      understanding of their possible effects on human health. However, data
      demonstrating the effect of CeO2 nanoparticles on the human skin melanoma cell
      remain scanty. In the current study, we determined the mechanism through which
      CeO2 nanoparticles (APS <25 nm) induce toxicity in human skin melanoma cells
      (A375). The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]
      and neutral red uptake assays showed concentration and time-dependent
      cytotoxicity of CeO2 nanoparticles in A375 cells. CeO2 nanoparticles
      significantly induced the generation reactive oxygen species (ROS) and
      malondialdehyde, superoxide dismutase, and decreased glutathione levels in A375
      cells. It was also observed that the CeO2 nanoparticles induced chromosomal
      condensation and caspase-3 activity. CeO2 nanoparticles exposed cells revealed
      the formation of DNA double-strand breakage as measured by percent tail DNA and
      olive tail moment through comet assay. The decline of cell viability, production
      of ROS, and DNA damage in A375 cells specifies that CeO2 nanoparticles have less
      capable to induce cyto and genotoxicity.

PMID- 25395199
TI  - Low Tidal Volume Ventilation in Patients Without Acute Lung Injury.
AB  - Acute respiratory distress syndrome is a life threatening respiratory condition
      characterized by breakdown of the alveolar-capillary barrier, leading to flooding
      of the alveolar space producing the classical chest radiograph of bilateral
      pulmonary infiltrates. In this study, we employed lung protective ventilation
      strategies in patients without acute lung injury (ALI) to determine whether
      mechanical ventilation with lower tidal volume would provide more clinical
      benefits to patients without ALI. 

PMID- 25395200
TI  - Clinically used selective oestrogen receptor modulators increase LDL receptor
      activity in primary human lymphocytes.
AB  - BACKGROUND AND PURPOSE: Treatment with selective oestrogen receptor modulators
      (SERMs) reduces low-density lipoprotein (LDL) cholesterol levels. We assessed the
      effect of tamoxifen, raloxifene and toremifene and their combinations with
      lovastatin on LDL receptor activity in lymphocytes from normolipidaemic and
      familial hypercholesterolaemic (FH) subjects, and human HepG2 hepatocytes and
      MOLT-4 lymphoblasts. EXPERIMENTAL APPROACH: Lymphocytes were isolated from
      peripheral blood, treated with different compounds, and 1,1'-dioctadecyl-3,3,3,3'
      tetramethylindocarbocyanine perchlorate (DiI)-labelled LDL uptake was analysed by
      flow cytometry. KEY RESULTS: Tamoxifen, toremifene and raloxifene, in this order,
      stimulated DiI-LDL uptake by lymphocytes by inhibiting LDL-derived cholesterol
      trafficking and subsequent down-regulation of LDL receptor expression.
      Differently to what occurred in HepG2 and MOLT-4 cells, only tamoxifen
      consistently displayed a potentiating effect with lovastatin in primary
      lymphocytes. The SERM-mediated increase in LDL receptor activity was not altered
      by the anti-oestrogen ICI 182,780 nor was it reproduced by 17beta-oestradiol.
      However, the tamoxifen-active metabolite endoxifen was equally effective as
      tamoxifen. The SERMs produced similar effects on LDL receptor activity in
      heterozygous FH lymphocytes as in normal lymphocytes, although none of them had a
      potentiating effect with lovastatin in heterozygous FH lymphocytes. The SERMs had
      no effect in homozygous FH lymphocytes. CONCLUSIONS AND IMPLICATIONS: Clinically
      used SERMs up-regulate LDL receptors in primary human lymphocytes. There is a
      mild enhancement between SERMs and lovastatin of lymphocyte LDLR activity, the
      potentiation being greater in HepG2 and MOLT-4 cells. The effect of SERMs is
      independent of oestrogen receptors but is preserved in the tamoxifen-active
      metabolite endoxifen. This mechanism may contribute to the cholesterol-lowering
      action of SERMs.

PMID- 25395202
TI  - Molecularly imprinted polymers based on SBA-15 for selective solid-phase
      extraction of baicalein from plasma samples.
AB  - Highly selective molecularly imprinted mesoporous silica polymer (SBA-15@MIP) for
      baicalein (BAI) extraction was synthesized using a surface molecular imprinting
      technique on the SBA-15 supporter. Computational simulation was used to predict
      the optimal functional monomer for the rational design of SBA-15@MIP. Meanwhile,
      high adsorption capacity was obtained when a suitable yield of molecularly
      imprinted polymers (MIPs) layer was grafted onto the surface of SBA-15.
      Characterization and performance tests of the obtained polymer revealed that SBA
      15@MIP possessed a highly ordered mesoporous structure, reached saturated
      adsorption within 60 min, and exhibited higher sorption capacity to the target
      molecule BAI compared with non-imprinted mesoporous silica polymer (SBA-15@NIP)
      and SBA-15. Finally, SBA-15@MIP was successfully applied to solid-phase
      extraction (SPE) coupled with high-performance liquid chromatography and
      ultraviolet detection (HPLC-UV) for the determination of trace BAI in plasma
      samples. Mean recoveries of BAI through the molecularly imprinted solid-phase
      extraction (MISPE) sorbent, non-imprinted solid-phase extraction (NISPE) sorbent,
      and SBA-15 solid-phase extraction (SBA-15-SPE) sorbent were 94.4, 22.7, and 10.7
      %, respectively, and the relative standard deviations were 2.9, 2.6, and 3.6 %,
      respectively. These results reveal that SBA-15@MIP as a SPE sorbent has good
      applicability to selectively separate and enrich trace BAI from complex samples. 

PMID- 25395201
TI  - Three-dimensional imaging of lipids and metabolites in tissues by nanospray
      desorption electrospray ionization mass spectrometry.
AB  - Three-dimensional (3D) imaging of tissue sections is a new frontier in mass
      spectrometry imaging (MSI). Here, we report on fast 3D imaging of lipids and
      metabolites associated with mouse uterine decidual cells and embryo at the
      implantation site on day 6 of pregnancy. 2D imaging of 16-20 serial tissue
      sections deposited on the same glass slide was performed using nanospray
      desorption electrospray ionization (nano-DESI)-an ambient ionization technique
      that enables sensitive localized analysis of analytes on surfaces without special
      sample pretreatment. In this proof-of-principle study, nano-DESI was coupled to a
      high-resolution Q-Exactive instrument operated at high repetition rate of >5 Hz
      with moderate mass resolution of 35,000 (m/Deltam at m/z 200), which enabled
      acquisition of the entire 3D image with a spatial resolution of ~150 MUm in less
      than 4.5 h. The results demonstrate localization of acetylcholine in the primary
      decidual zone (PDZ) of the implantation site throughout the depth of the tissue
      examined, indicating an important role of this signaling molecule in
      decidualization. Choline and phosphocholine-metabolites associated with cell
      growth-are enhanced in the PDZ and abundant in other cellular regions of the
      implantation site. Very different 3D distributions were obtained for fatty acids
      (FA), oleic acid and linoleic acid (FA 18:1 and FA 18:2), differing only by one
      double bond. Localization of FA 18:2 in the PDZ indicates its important role in
      decidualization while FA 18:1 is distributed more evenly throughout the tissue.
      In contrast, several lysophosphatidylcholines (LPC) observed in this study show
      donut-like distributions with localization around the PDZ. Complementary
      distributions with minimal overlap were observed for LPC 18:0 and FA 18:2 while
      the 3D image of the potential precursor phosphatidylcholine 36:2 (PC 36:2) showed
      a significant overlap with both LPC 18:0 and FA 18:2. 

PMID- 25395203
TI  - Determination of oxygenated and native polycyclic aromatic hydrocarbons in urban
      dust and diesel particulate matter standard reference materials using pressurized
      liquid extraction and LC-GC/MS.
AB  - The objective of this study was to develop a novel analytical chemistry method,
      comprised of a coupled high-performance liquid chromatography-gas
      chromatography/mass spectrometry system (LC-GC/MS) with low detection limits and
      high selectivity, for the identification and determination of oxygenated
      polycyclic aromatic hydrocarbons (OPAHs) and polycyclic aromatic hydrocarbons
      (PAHs) in urban air and diesel particulate matter. The linear range of the four
      OPAHs, which include 9,10-anthraquinone, 4H-cyclopenta[def]phenanthrene-4-one,
      benzanthrone, and 7,12-benz[a]anthraquinone, was 0.7 pg-43.3 ng with limits of
      detection (LODs) and limits of quantification (LOQs) on the order of 0.2-0.8 and
      0.7-1.3 pg, respectively. The LODs in this study are generally lower than values
      reported in the literature, which can be explained by using large-volume
      injection. The recoveries of the OPAHs spiked onto glass fiber filters using two
      different pressurized liquid extraction (PLE) methods were in the ranges of 84
      107 and 67-110 %, respectively. The analytical protocols were validated using the
      following National Institute of Standards and Technology standard reference
      materials: SRM 1649a (Urban Dust), SRM 1650b (Diesel Particulate Matter), and SRM
      2975 (Diesel Particulate Matter, Industrial Forklift). The measured mass
      fractions of the OPAHs in the standard reference materials (SRMs) in this present
      study are higher than the values from the literature, except for benzanthrone in
      SRM 1649a (Urban Dust). In addition to the OPAHs, 44 PAHs could be detected and
      quantified from the same particulate extract used in this protocol. Using data
      from the literature and applying a two-sided t test at the 5 % level using
      Bonferroni correction, significant differences were found between the tested PLE
      methods for individual PAHs. However, the measured mass fractions of the PAHs
      were comparable, similar to, or higher than those previously reported in the
      literature. 

PMID- 25395205
TI  - Artificial neural network prediction of multilinear gradient retention in
      reversed-phase HPLC: comprehensive QSRR-based models combining categorical or
      structural solute descriptors and gradient profile parameters.
AB  - A multilayer artificial neural network (ANN) is used to model the reversed-phase
      liquid chromatography retention times of 16 selected compounds, including
      purines, pyrimidines and nucleosides. The analysed data, taken from literature,
      were collected in acetonitrile-water eluents under the application of 16
      different multilinear gradients. The parameters describing the gradient profile
      together with solute descriptors are considered as the independent variables of
      an ANN-based model providing the retention time as response. Categorical
      variables or, alternatively, a selected set of molecular descriptors of
      computational origin are adopted to represent the solutes. Network training,
      validation and testing are performed preliminarily using data of 12, 2 and 4
      gradients, respectively and successively, to investigate model performance under
      more severe calibration conditions, with data of 9, 2 and 7 gradients. The
      proposed approach allows a quite accurate prediction of retention times of the
      target analytes in external multilinear gradients. Categorical variables can
      successfully represent the target solutes when the model is called to transfer
      retention data from calibration to external gradients. In particular, using a
      five-dimensional bit string to represent the analytes, mean errors on retention
      times are 2 and 3 % under the most and less favourable calibration conditions,
      respectively. A comparable performance is observed if the categorical variables
      are replaced by five molecular descriptors, selected by a genetic algorithm
      within a large set of structural variables of computational origin. 

PMID- 25395204
TI  - A simple MALDI plate functionalization by Vmh2 hydrophobin for serial multi
      enzymatic protein digestions.
AB  - The development of efficient and rapid methods for the identification with high
      sequence coverage of proteins is one of the most important goals of proteomic
      strategies today. The on-plate digestion of proteins is a very attractive
      approach, due to the possibility of coupling immobilized-enzymatic digestion with
      direct matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF)
      mass spectrometry (MS) analysis. The crucial step in the development of on-plate
      immobilization is however the functionalization of the solid surface. Fungal self
      assembling proteins, the hydrophobins, are able to efficiently functionalize
      surfaces. We have recently shown that such modified plates are able to absorb
      either peptides or proteins and are amenable to MALDI-TOF-MS analysis. In this
      paper, the hydrophobin-coated MALDI sample plates were exploited as a lab-on
      plate for noncovalent immobilization of enzymes commonly used in protein
      identification/characterization, such as trypsin, V8 protease, PNGaseF, and
      alkaline phosphatase. Rapid and efficient on-plate reactions were performed to
      achieve high sequence coverage of model proteins, particularly when performing
      multiple enzyme digestions. The possibility of exploiting this direct on-plate
      MALDI-TOF/TOF analysis has been investigated on model proteins and, as proof of
      concept, on entire whey milk proteome. 

PMID- 25395206
TI  - [Ultrasound diagnostics in ophthalmology (standardized echography): part 2:
      diseases of the orbit - ultrasound biomicroscopy diagnostics].
AB  - Ultrasound diagnostics have been one of the most important noninvasive
      supplementary diagnostic procedures in ophthalmology for many decades and are
      indispensable for many intraocular and orbital diseases. When the echography
      examination and analysis of the echograms obtained are correctly carried out,
      ultrasound diagnostics are characterized by a high measure of specificity and
      sensitivity. 

PMID- 25395207
TI  - Asbestos exposure among transmission mechanics in automotive repair shops.
AB  - OBJECTIVES: Asbestos has been used in a broad variety of industrial products,
      including clutch discs of the transmission system of vehicles. Studies conducted
      in high-income countries that have analyzed personal asbestos exposures of
      transmission mechanics have concluded that these workers are exposed to asbestos
      concentrations in compliance with the US Occupational Safety and Health
      Administration (US OSHA) occupational standards. Clutch facings are the friction
      component of clutch discs. If clutch facings are sold separated from the support,
      they require manipulation before installation in the vehicle. The manipulation of
      asbestos containing clutch facings is performed by a group of mechanics known as
      riveters, and includes drilling, countersinking, riveting, sanding, and
      occasionally grinding, tasks that can potentially release asbestos fibers,
      exposing the mechanics. These manipulation activities are not reported in studies
      conducted in high-income countries. This study analyzes personal asbestos
      exposures of transmission mechanics that manipulate clutch facings. METHODS: Air
      sampling campaigns in two transmission repair shops (TRS) were conducted in
      November 2012 and July 2013 in Bogota, Colombia. Four workers employed in these
      TRS were sampled (i.e. three riveters and one supervisor). Personal samples (n =
      39), short-term personal samples (n = 49), area samples (n = 52), blank samples
      (n = 8), and background samples (n = 2) were collected in both TRS during 3-5
      consecutive days, following US National Institute for Occupational Safety and
      Health (US NIOSH) methods 7400 and 7402. Asbestos samples were analyzed by an
      American Industrial Hygiene Association accredited laboratory. RESULTS: On at
      least one of the days sampled, all riveters were exposed to asbestos
      concentrations that exceeded the US OSHA permissible exposure limit or the
      Colombian permissible limit value. Additionally, from the forty-seven 30-min
      short-term personal samples collected, two (4.3%) exceeded the US OSHA excursion
      limit of 1 f cm(-3). CONCLUSIONS: In this study, we identified that the working
      conditions and use of asbestos containing transmission products expose
      transmission mechanics to asbestos concentrations that exceed both the Colombian
      and OSHA standards. The potential consequences for the health of these workers
      are of great concern.

PMID- 25395208
TI  - Simulating an investigative study of clinical cancer samples: use of tissue
      slides and PCR-based promoter-hypermethylation analysis.
AB  - Topics on the molecular basis underlying cancer are quite popular among students.
      Also, excellent textbooks abound that provide interesting materials for
      discussion during lectures and tutorials about major events leading to cancer
      formation and progression. However, much less is available for students to
      conduct experiments for the analysis of cancer samples in undergraduate modules
      where there is a limited time-frame. Given the difficulty of working with cancer
      samples and the scarcity of good samples even in the clinical laboratories, it is
      impossible to run large-class practicals using patients' samples. Here, we
      describe the use of tissue slides in combination with polymerase-chain reaction
      (PCR) as a means of simulating an investigative approach to supplement students'
      learning of clinical research. By using tissue slides for histo-pathological
      examinations and specific budding yeast genomic DNA and primers adapted to
      demonstrate methylation-specific PCR, we designed an inquiry-based lab session to
      simulate the clinical investigation of a cohort of biopsies that students could
      analyze in a one-session practical.

PMID- 25395209
TI  - SIN3A mutations are rare in men with azoospermia.
AB  - A loss of function of the murine Sin3A gene resulted in male infertility with
      Sertoli cell-only syndrome (SCOS) phenotype in mice. Here, we investigated the
      relevance of this gene to human male infertility with azoospermia caused by SCOS.
      Mutation analysis of SIN3A in the coding region was performed on 80 Japanese
      patients. However, no variants could be detected. This study suggests a lack of
      association of SIN3A gene sequence variants with azoospermia caused by SCOS in
      humans.

PMID- 25395210
TI  - Physical activity interferes with the immunomodulatory effect of the
      antineoplastic drug NSC631570.
AB  - OBJECTIVE: The aim of the work was to evaluate the effect of moderate physical
      exercise on the response of circulating phagocytes to the antineoplastic drug NSC
      631570. METHODS: Eight healthy adult men aged 23 +/- 2 years were recruited to
      participate in the study; NSC 631570 was administered i.v. in a single
      therapeutic dose; blood samples were collected before and after the drug
      administration; the moderate physical exercise programme included 50 slow squats;
      total leukocyte, neutrophil and lymphocyte counts were determined using the
      haematological analyser; intracellular ROS generation and phagocytic activity of
      circulating monocytes and granulocytes were analysed by flow cytometry; PPAR
      gamma protein expression was evaluated by Western blot. RESULTS: introduction of
      NSC 631570 in an inpatient setting was associated with a decrease in phagocyte
      endocytic activity along with an increase in ROS generation. Drug injection in an
      outpatient setting was accompanied by a significant increase in monocyte and
      granulocyte phagocytosis along with a decrease in the daily mean of ROS
      generation as well as by a decrease in monocyte reactivity reserve after
      stimulation in vitro. PPAR-gamma expression in circulating monocytes was
      significantly decreased after the drug administration in an inpatient setting and
      was slightly increased in active participants after the drug injection.
      CONCLUSION: NSC 631570 causes M1 (N1) shift of phagocytes after in vivo
      introduction. Moderate physical exercise exerts a negative effect on the
      immunomodulatory action of NSC 631570 by abrogating M1 (N1) shift of circulating
      phagocytes. One of the reasons for such an effect could be an increase in PPAR
      gamma expression by phagocytes.

PMID- 25395211
TI  - Vildagliptin induces beta-cell neogenesis and improves the lipid profile in a
      later phase of type 1 diabetes.
AB  - Recently, the inhibitor dipeptidyl peptidase-4 has been reported to be beneficial
      in the treatment of type 1 diabetes mellitus. For the first time, this study
      evaluates the effect of vildagliptin on beta -cell neogenesis and lipid
      homeostasis in a later phase of type 1 diabetes. In Fischer rats, diabetes was
      induced with alloxan. After confirmation of diabetic status, the animals received
      no treatment for 30 days to establish a late phase of the disease these animals.
      After this period, the animals were treated with vildagliptin via gavage for 30
      consecutive days. Fasting blood glucose, serum insulin, lipid profile and
      pancreatic histology were evaluated. Treatment with vildagliptin increased serum
      levels of insulin, improved beta cell function and improved the lipid profile.
      Histological analyses revealed that this treatment increased the populations of
      pancreatic beta-cells in the diabetic animals. The treatment was effective in
      improving the mass and function of beta-cells and contributed to lipid
      homeostasis, in an experimental model of type 1 diabetes. 

PMID- 25395212
TI  - Extracellular production of the oncolytic enzyme, L-asparaginase, by newly
      isolated Streptomyces sp. strain NEAE-95 as potential microbial cell factories:
      optimization of culture conditions using response surface methodology.
AB  - L-asparaginase is an effective anti-neoplastic agent used in chemotherapy of
      acute lymphoblastic leukemia. One hundred and thirty actinomycete isolates were
      isolated from several soil samples collected from different localities in Egypt.
      All these isolates were purified and evaluated for their ability to produce L
      asparaginase activity. Among them, strain NEAE-95 was selected and identified as
      Streptomyces parvus strain NEAE-95 based on morphological, cultural,
      physiological characteristics and 16S rRNA sequence. The sequence was deposited
      in the NCBI GenBank database under accession number KJ200341. L-asparaginase
      production by Streptomyces parvus NEAE-95 was optimized in shake flask culture.
      The Plackett-Burman statistical design was used for initial screening of sixteen
      factors for their significance on L-asparaginase production. Among the variables
      screened, incubation time, L-asparagine and yeast extract had significant effects
      on L-asparaginase production. The levels of these significant variables and their
      interaction effects were optimized by Box-Behnken statistical design. As a
      result, the maximal L-asparaginase production was achieved at the following
      fermentation conditions: g/L (dextrose 2, starch 20, L-asparagine 14, KNO3 2,
      yeast extract 2, K2HPO4 2, MgSO4.7H2O 0.1, NaCl 0.1, FeSO4.7H2O 0.01), pH 7,
      temperature 30 degrees C, agitation speed 200 rpm, inoculum size 2%, v/v and
      incubation time 8 days. 

PMID- 25395214
TI  - "Current Biotechnological Approaches for Studying G Protein Coupled Receptor
      Structure, Function and Signaling"

PMID- 25395213
TI  - Milk fermented with a 15-lipoxygenase-1-producing Lactococcus lactis alleviates
      symptoms of colitis in a murine model.
AB  - Inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative
      colitis, is characterized by extensive inflammation due to dysregulation of the
      innate and adaptive immune system whose exact etiology is not yet completely
      understood. Currently there is no cure for IBD, thus the search for new molecules
      capable of controlling IBD and their delivery to the site of inflammation are the
      goal of many researchers. The aim of this work was to evaluate the anti
      inflammatory effect of the administration of milks fermented by a Lactococcus
      (L.) lactis strain producing 15-lipoxygenase-1 (15-LOX-1) using a
      trinitrobenzenesulfonic acid-induced IBD mouse model. The results obtained
      demonstrated that 15-LOX-1 producing L. lactis was effective in the prevention of
      the intestinal damage associated to inflammatory bowel disease in a murine model.
      The work also confirmed previous studies showing that fermented milk is an
      effective form of administration of recombinant lactic acid bacteria expressing
      beneficial molecules. 

PMID- 25395215
TI  - Encapsulation of chondrocytes in high-stiffness agarose microenvironments for in
      vitro modeling of osteoarthritis mechanotransduction.
AB  - In articular cartilage, chondrocytes reside within a gel-like pericellular matrix
      (PCM). This matrix provides a mechanical link through which joint loads are
      transmitted to chondrocytes. The stiffness of the PCM decreases in the most
      common degenerative joint disease, osteoarthritis. To develop a system for
      modeling the stiffness of both the healthy and osteoarthritic PCM, we determined
      the concentration-stiffness relationships for agarose. We extended these results
      to encapsulate chondrocytes in agarose of physiological stiffness. Finally, we
      assessed the relevance of stiffness for chondrocyte mechanotransduction by
      examining the biological response to mechanical loading for cells encapsulated in
      low- and high-stiffness gels. We achieved agarose equilibrium stiffness values as
      large as 51.3 kPa. At 4.0% agarose, we found equilibrium moduli of 34.3 +/- 1.65
      kPa, and at 4.5% agarose, we found equilibrium moduli of 35.7 +/- 0.95 kPa.
      Cyclical tests found complex moduli of ~100-300 kPa. Viability was >96% for all
      studies. We observed distinct metabolomic responses in >500 functional small
      molecules describing changes in cell physiology, between primary human
      chondrocytes encapsulated in 2.0 and 4.5% agarose indicating that the gel
      stiffness affects cellular mechanotransduction. These data demonstrate both the
      feasibility of modeling the chondrocyte pericellular matrix stiffness and the
      importance of the physiological pericellular stiffness for understanding
      chondrocyte mechanotransduction. 

PMID- 25395216
TI  - Effects of Age, Gender and Level of Co-contraction on Elbow and Shoulder
      Rotational Stiffness and Damping in the Impulsively End-Loaded Upper Extremity.
AB  - Whether an arm will buckle under an impulsive end-load should partly depend on
      the elastic and viscous properties of the pretensed arm muscles. In measuring
      these properties we hypothesized that neither age, gender, nor muscle pre
      contraction level would affect the bilinear elbow or shoulder lumped rotational
      stiffness or damping parameters in the impulsively end-loaded upper extremity of
      38 healthy men and women. Subjects were instructed to preactivate triceps to
      either 25, 50 or 75% of maximum myoelectric activity levels. Then a standardized
      impulsive end-load was applied via a 6-axis load cell to the wrist of the
      slightly flexed arm in the prone posture. Arm kinematic responses were acquired
      at 280 Hz and an inverse dynamics analysis was used to estimate the bilinear
      rotational stiffnesses and damping parameters at the elbow and shoulder. The
      results show that pre-contraction level affected normalized joint rotational
      stiffness and damping coefficients (p < 0.02). Age affected the initial stiffness
      for the elbow (p < 0.05), and gender affected that of the shoulder in the
      sagittal plane (p < 0.006). Arm muscle strength was positively related to
      normalized stiffness at the elbow, but not the shoulder. We conclude that age,
      gender and pre-contraction level each affect the viscoelastic behavior of the end
      loaded upper extremity in healthy adults. 

PMID- 25395217
TI  - First salvage treatment of germ cell tumor patients with bone metastases:
      retrospective analysis of a large international database.
AB  - PURPOSE: To retrospectively analyze clinical characteristics, prognostic factors,
      and optimal treatment of patients with bone metastases (BM) of germ cell tumors
      (GCT) at first relapse. METHODS: One hundred and four GCT patients with BM were
      identified from the IPFSG database containing 1,594 patients at first relapse.
      Within this database, all patients experienced unequivocal relapse/progression
      after cisplatin-based chemotherapy and had received either conventional (CD-CTX)
      or high-dose chemotherapy (HD-CTX) as first salvage treatment. RESULTS: At
      relapse, eight patients (8 %) had BM only, concomitant relapse with lung, brain,
      liver and/or nodal metastases were present in 40 (39 %), 6 (6 %), 27 (26 %), and
      69 (66 %) pts, respectively. Patients clustered over all IPFSG subgroups, and the
      IPFSG score could be confirmed. Salvage treatment was CD-CTX in 35 and HD-CTX in
      69 patients. Overall response (CR, PR) rate to salvage chemotherapy was 81 % (HD
      CTX) versus 43 % (CD-CTX; p < 0.001). Median follow-up was 14 months (mos; range
      1-161). Both, median PFS and OS, were higher after HD-CTX compared to CD-CTX [PFS
      9 (95 % CI 6-12) vs. 5 (3-7) mos (p < 0.01); OS 18 (12-24) vs. 13 (8-18) mos (p =
      0.078)]. CONCLUSIONS: GCT patients relapsing with BM have a dismal outcome.
      Retrospectively, first salvage HD-CTX seems to improve treatment response and
      outcome. Further evaluation of characteristics and treatment of GCT patients with
      BM is warranted.

PMID- 25395218
TI  - Developing trends in the intestinal transplant waitlist.
AB  - The United Network for Organ Sharing database was examined for trends in the
      intestinal transplant (ITx) waitlist from 1993 to 2012, dividing into listings
      for isolated ITx versus liver-intestine transplant (L-ITx). Registrants added to
      the waitlist increased from 59/year in 1993 to 317/year in 2006, then declined to
      124/year in 2012; Spline modeling showed a significant change in the trend in
      2006, p < 0.001. The largest group of registrants, <1 year of age, determined the
      trend for the entire population; other pediatric age groups remained stable,
      adult registrants increased until 2012. The largest proportion of new registrants
      were for L-ITx, compared to isolated ITx; the change in the trend in 2006 for L
      ITx was highly significant, p < 0.001, but not isolated ITx, p = 0.270. New
      registrants for L-ITx, <1 year of age, had the greatest increase and decrease.
      New registrants for isolated ITx remained constant in all pediatric age groups.
      Waitlist mortality increased to a peak around 2002, highest for L-ITx, in
      patients <1 year of age and adults. Deaths among all pediatric age groups
      awaiting L-ITx have decreased; adult L-ITx deaths have dropped less dramatically.
      Improved care of infants with intestinal failure has led to reduced referrals for
      L-ITx. 

PMID- 25395219
TI  - Oxidative status and plasma lipid profile in beta-thalassemia patients.
AB  - Abstract beta-Thalassemia (beta-thal) is a genetic disorder, representing a major
      health problem in Algeria. It is associated with altered lipid levels and a state
      of oxidative stress that can lead to cardiac complications and premature death.
      We examined the plasma lipid profile and redox status of 46 patients with beta
      thal major (beta-TM) and beta-thal intermedia (beta-TI) compared to 36 healthy
      subjects. Plasma lipids including total cholesterol (TC), triglycerides (TG),
      high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein
      cholesterol (LDL-C) were investigated. Oxidative status was evaluated by
      measuring malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT)
      activity. The potential relationships between these parameters and the hemoglobin
      (Hb) blood concentrations, serum ferritin, duration and frequency of transfusion,
      splenectomy as well as age, were examined. Our data indicated that the study
      patients were under increased state of oxidative stress associated with
      hypertriglyceridemia, and hypocholesterolemia. The CAT activity was negatively
      correlated with Hb concentration and LDL-C/TG ratio and positively with years of
      transfusion. The elevated TC/HDL-C ratio particularly in beta-TM patients who
      were younger, correlated positively with ferritinemia and triglyceride levels and
      suggested an increased coronary risk. This heightened risk state should lead to
      the inclusion of this index (TC/HDL-C) in clinical management, particularly in
      splenectomized patients. 

PMID- 25395220
TI  - Uncovering methods for the prevention of protein aggregation and improvement of
      product quality in a transient expression system.
AB  - Mammalian expression systems are used routinely for the production of recombinant
      proteins as therapeutic molecules as well as research tools. Transient expression
      has become increasingly popular in recent years due to its rapid timeline and
      improvements in expression level. While improvements to transient expression
      systems have focused mainly on the level of protein expression, the aspect of
      protein quality has received little attention. The removal of undesirable
      products, such as aggregation, depends primarily on purification, requiring
      additional cumbersome steps, which can lead to a lower product yield and longer
      timelines. In this study, we show that reducing the level of transcription by
      transfecting at a lower gene dose improves the quality of secreted molecules
      prone to aggregation. For gene dosing to have this effect, it is critical for the
      carrier DNA to be an empty vector containing the same elements as the gene
      containing plasmid. This approach can be used in combination with a temperature
      shift to hypothermic conditions during production to enhance the effect. The
      observed improvements not only minimized aggregation levels, but also generated
      products with overall superior quality, including more homogeneous signal peptide
      cleavage and N-linked glycosylation profiles. These techniques have produced a
      similar improvement in product quality with a variety of other molecules,
      suggesting that this may be a general approach to enhance product quality from
      transient expression systems.

PMID- 25395221
TI  - Child Maltreatment History and Response to CBT Treatment in Depressed Mothers
      Participating in Home Visiting.
AB  - Child maltreatment contributes to depression in adults. Evidence indicates that
      such experiences are associated with poorer outcomes in treatment. Mothers in
      home visiting programs display high rates of depression and child maltreatment
      histories. In-Home Cognitive Behavioral Therapy (IH-CBT) was developed to treat
      maternal depression in home visiting. The purpose of this study was to examine
      the moderating effects of child maltreatment history on depression, social
      functioning, and parenting in mothers participating in a clinical trial of IH
      CBT. Ninety-three depressed mothers in home visiting between 2 and 10 months
      postpartum were randomly assigned to IH-CBT (n = 47) plus home visiting or
      standard home visiting (SHV; n = 46). Mothers were identified via screening and
      then confirmation of major depressive disorder diagnosis. Measures of child
      maltreatment history, depression, social functioning, and parenting were
      administered at pre-treatment, post-treatment, and 3-month follow-up. Results
      indicated high rates of maltreatment in both conditions relative to the general
      population. Mixed model analyses found a number of main effects in which
      experiences of different types of trauma were associated with poorer functioning
      regardless of treatment condition. Evidence of a moderating effect of
      maltreatment on treatment outcomes was found for physical abuse and parenting and
      emotional abuse and social network size. Future research should focus on
      increasing the effectiveness of IH-CBT with depressed mothers who have
      experienced child maltreatment. 

PMID- 25395222
TI  - Police Officer Schema of Sexual Assault Reports: Real Rape, Ambiguous Cases, and
      False Reports.
AB  - While extensive research has studied sexual assault reporting behaviors and
      described negative experiences with the criminal justice system among victim
      survivors, fewer studies have explored police officer attitudes, knowledge, and
      thought processes that may affect victims' perceptions of negative interactions
      and unsatisfactory outcomes within reported sexual assault cases. This study
      explores police officer understanding of the definition of sexual assault and
      characteristics that influence their perceptions and response. Ten police
      officers were interviewed within one police department in a midsized city in the
      Great Lakes region. The study uses a modified grounded theory approach. Findings
      suggest that officers employ distinct schema of reported sexual assaults. Case
      characteristics, perceived credibility of the victim, and types of evidence
      formed categorizations of false reports, ambiguous cases, and legitimate sexual
      assaults. Police officers describe the ways in which perceptions of the case may
      or may not influence the response and point to areas for improvement within
      police procedure. The study findings provide insight into recommendations for
      improved police interviewing and response to reported sexual assaults. 

PMID- 25395224
TI  - Dating Violence and Substance Use: Exploring the Context of Adolescent
      Relationships.
AB  - The connection between adolescent dating violence (ADV) and substance use is
      important to consider because of the serious consequences for teens who engage in
      these behaviors. Although prior research shows that these two health problems are
      related, the context in which they occur is missing, including when (i.e., the
      timeline) in the relationship these events occur. To fill this gap, eight sex
      specific focus groups were conducted with 39 high school-aged teens, all of whom
      had experienced prior relationship violence. Adolescents discussed using alcohol
      and/or drugs at the start of the dating relationship and after the relationship
      ended as a way to cope with the break-up. Alcohol and drugs were also used
      throughout to cope with being in an abusive relationship. The intersection of ADV
      and substance use occurred during instances when both partners were using alcohol
      and/or drugs, as well as when only one partner was using. These findings provide
      support for prevention and intervention programs that consider the intersection
      of ADV and substance use. 

PMID- 25395223
TI  - Feasibility of an HIV/STI Risk-Reduction Program for Incarcerated Women Who Have
      Experienced Interpersonal Violence.
AB  - HIV and other sexually transmitted infections (STIs) and interpersonal violence
      (IV; e.g., childhood abuse, partner violence, and rape) victimization are
      significant and interconnected public health problems facing incarcerated women.
      We adapted a best-evidence HIV-prevention intervention for women (the Women's
      CoOp) to address sexual safety among incarcerated women with histories of
      interpersonal violence victimization. The standard Women's CoOp teaches safe sex,
      substance use harm reduction, and violence prevention information and skills
      needed to empower women to make more intentional decisions about their safety. We
      also incorporated strategies to increase affect management, social support, and
      access to community resources. This resulted in the first trauma-focused HIV
      prevention intervention for women that directly addresses the sequelae of IV
      (such as affect dysregulation in sexual situations) within the context of HIV
      harm reduction. This manuscript describes the rationale, feasibility,
      acceptability, and pre-post outcomes of this intervention among 14 women nearing
      release from prison in two state prison systems. Assessments took place at
      baseline, prior to release, and at 2-, 5-, and 8 months after release. The
      intervention overall and each of its components were feasible and acceptable.
      Participants' number of unprotected sexual occasions, post-traumatic stress
      disorder symptoms, and depressive symptoms decreased significantly from baseline
      to post-release. Effectiveness in obtaining resources increased significantly
      from baseline to post-release. Because pre-post measurements of outcomes are
      confounded with incarceration and subsequent release in this preliminary study, a
      randomized controlled trial is needed to establish the efficacy of this tailored
      intervention. 

PMID- 25395225
TI  - Adult Sexual Experiences as a Mediator Between Child Abuse and Current Secretory
      Immunoglobulin A Levels.
AB  - The current study investigated whether a history of child abuse is a predictor of
      adult immune status, with unwanted adult sexual experiences as a proximal
      mediator. Participants included 89 young adult women (M(age) = 19.24) who were
      classified as having experienced no child abuse, child physical abuse, or child
      sexual abuse, based upon self-reported victimization history before 14 years of
      age. Participants also reported on unwanted sexual experiences in young adulthood
      and provided four saliva samples, which were collected over two consecutive days
      to determine secretory immunoglobulin A (sIgA). Age and negative life events were
      considered as covariates. The results indicated that adult sexual victimization
      partially mediated the relationship between child abuse (physical and sexual) and
      sIgA. Specifically, child abuse experiences predicted more adult sexual
      victimization experiences, which in turn predicted lower sIgA levels. These
      findings support long-term health effects of victimization, and suggest that the
      influence of child abuse on sIgA may be perpetuated through adult victimization.
      Prevention efforts should aim to empower child maltreatment survivors with skills
      to prevent adult re-victimization. By thwarting future unwanted sexual
      experiences in adulthood, individuals will be better protected from the health
      impairments associated with early abuse experiences.

PMID- 25395226
TI  - The Relationship Between Sexual Victimization and Year in School in U.S.
      Colleges: Investigating the Parameters of the "Red Zone".
AB  - It is the conventional wisdom among some universities that the highest risk of
      sexual assault is in the first or possibly second year in school. While initially
      belief in this pattern was primarily based on anecdote, recently some attempts
      have been made to more systematically and quantitatively test the existence of a
      "red zone," a time of heightened risk of sexual assault sometime near the
      beginning of a female student's time at the college. However, most of these
      studies have been conducted with relatively small convenience samples from single
      schools and have had conflicting results. Here, I test the red zone hypothesis
      using self-reported sexual victimization data with a large sample (~16,000) drawn
      from 22 schools as part of the Online College Social Life Survey. To investigate
      the specific mechanisms responsible for the red zone, I separately test for the
      existence of a red zone for four different types of sexual victimizations:
      physically forced intercourse, attempted forced intercourse, unwanted intercourse
      when incapacitated, and unwanted intercourse due to verbal pressure. Within these
      categories, I separately address sexual victimization that occurred while hanging
      out and sexual victimization during a party. Prior literature has emphasized the
      role of parties in the increased risk of assault for freshman. While I find some
      evidence for this in the higher estimates for sexual victimization at a party,
      the freshman effect remains for other types of sexual victimizations, suggesting
      that the red zone is not easily attributable to a single mechanistic cause, but
      to more generalizable factors. With one exception, I find that the red zone does
      not extend into the sophomore year. 

PMID- 25395227
TI  - Developing resilience throughout the continuum of medical education.

PMID- 25395228
TI  - Acquiring evidence-based medicine and research skills in the undergraduate
      medical curriculum: three different didactical formats compared.
AB  - Medical schools have recently witnessed a call for authentic research activities
      that equip students with the skills required for evidence-based medicine (EBM)
      and research. Because it is not always possible to make such activities available
      as a part of the curriculum, evaluating the effectiveness of the various choices
      of traditional and authentic EBM and research skills courses is essential. This
      study's purpose was to evaluate students' perceived EBM and research skill
      acquisition in three different courses in a Dutch medical school. Self-reported
      surveys were conducted among 163 Dutch medical undergraduates who participated in
      an undergraduate research project, a basic EBM skills elective, or a traditional
      lecture-based skills course. MANCOVA was employed to test for group differences
      in perceived skill acquisition. Students who finished their research project
      perceived themselves as more experienced in writing and information retrieval
      skills than students who participated in the lecture-based course or basic skills
      elective. Students in the lecture-based course identified themselves as being the
      most experienced in critical judgment. No group differences were found for
      overall gains. Authentic research activities may have benefits over traditional
      lecture-based courses in the undergraduate medical curriculum, especially in
      terms of equipping students with writing and information retrieval skills. 

PMID- 25395229
TI  - "You teach us to listen,... but you don't teach us about suffering": self-care
      and resilience strategies in medical school curricula.
AB  - This article examines the pre-vocational preparation of doctors to cope with the
      demands of clinical practice, drawing on literature from across a number of
      domains: mental health, psychological stress among medical students and medical
      practitioners; and self-care strategies in medicine curricula. High rates of
      psychological distress in medical students and medical practitioners were
      consistently reported. A number of questions remain pertinent to medical
      education: how does the experience of medical education impact on this level of
      distress, and possibly exacerbate pre-existing student vulnerabilities? What will
      help future doctors respond to, and cope with, suffering in their patients? Can
      the formal curriculum build resilience? Medical schools and educators have a
      responsibility to address these questions and to provide effective self-care
      curricula. In this review promising interventions such as mindfulness training
      are reported, frameworks to guide self-awareness in medical students are
      suggested, and recommendations for a self-care curriculum are made. 

PMID- 25395230
TI  - Speciality preferences in Dutch medical students influenced by their anticipation
      on family responsibilities.
AB  - Physician gender is associated with differences in the male-to-female ratio
      between specialities and with preferred working hours. We explored how graduating
      students' sex or full-time or part-time preference influences their speciality
      choice, taking work-life issues into account. Graduating medical students at
      Radboud University Medical Centre, the Netherlands participated in a survey (2008
      2012) on career considerations. Logistic regression tested the influence of sex
      or working hour preference on speciality choice and whether work-life issues
      mediate. Of the responding students (N = 1,050, response rate 83, 73.3 % women),
      men preferred full-time work, whereas women equally opted for part time. More men
      chose surgery, more women family medicine. A full-time preference was associated
      with a preference for surgery, internal medicine and neurology, a part-time
      preference with psychiatry and family medicine. Both male and female students
      anticipated that foremost the career of women will be negatively influenced by
      family life. A full-time preference was associated with an expectation of
      equality in career opportunities or with a less ambitious partner whose career
      would affect family life. This increased the likelihood of a choice for surgery
      and reduced the preference for family medicine among female students. Gender
      specifically plays an important role in female graduates' speciality choice
      making, through considerations on career prospects and family responsibilities. 

PMID- 25395231
TI  - Facilitating the initiation of the physician's professional identity: Cornell's
      urban semester program.
AB  - Calling for major reform in medical education, the Carnegie Institute report
      'Educating Physicians' espoused the importance of assisting student trainees in
      forming their professional identities. Here, we consider the question: At what
      educational stage should future physicians begin this process? The literature
      suggests that the process begins when students matriculate in medical school; we
      posit, however, that premedical students can begin their proto-professional
      development as college undergraduates. We describe here the pedagogy of Cornell
      University's urban semester program (USP), which enables college students to
      participate in shadowing experiences as part of an integrated structured study
      programme. USP students report improved communicative competency, changes in
      their perceptions and attitudes toward medical practice, and powerful influences
      on their personal and professional development upon completion of the programme.
      We suggest the solution to the question of 'When and under what conditions should
      shadowing take place?' is to utilize a structure that combines the exposure of
      college students to the professional environment with a didactic and self
      reflective curriculum, thereby supporting students in their early professional
      development. We conclude that educational efforts aimed at developing
      professional identity and behaviour can begin before students enter medical
      school. 

PMID- 25395232
TI  - Incorporation of graphene oxide nanosheets into boronate-functionalized polymeric
      monolith to enhance the electrochromatographic separation of small molecules.
AB  - Graphene oxide (GO) nanosheets were incorporated into an organic polymer monolith
      containing 3-acrylamidophenylboronic acid (AAPBA) and pentaerythritol triacrylate
      (PETA) to form a novel monolithic stationary phase for CEC. The effects of the
      mass ratio of AAPBA/PETA, the amount of GO, and the volume of porogen on the
      morphology, permeability and pore properties of the prepared poly(AAPBA-GO-PETA)
      monoliths were investigated. A series of test compounds including amides,
      alkylbenzenes, polycyclic aromatics, phenols, and anilines were used to evaluate
      and compare the separation performances of the poly(AAPBA-GO-PETA) and the parent
      poly(AAPBA-co-PETA) monoliths. The results indicated that incorporation of GO
      into monolithic column exhibited much higher resolutions (>1.5) and column
      efficiency (62,000 ~ 110,000 plates/m for toluene, DMF, formamide, and thiourea)
      than the poly(AAPBA-co-PETA). The successful application in isocratic separation
      of peptides suggests the potential of the GO incorporated monolithic column in
      complex sample analysis. In addition, the reproducibility and stability of the
      prepared poly(AAPBA-GO-PETA) monolith was assessed. The run-to-run, column-to
      column and batch-to-batch reproducibilities of this monolith for alkylbenzenes'
      retention were satisfactory with the RSDs less than 1.8% (n = 5), 3.7% and 5.6%
      (n = 3), respectively, indicating the effectiveness and practicability of the
      proposed method.

PMID- 25395233
TI  - Characterization of the microbial community in different types of Daqu samples as
      revealed by 16S rRNA and 26S rRNA gene clone libraries.
AB  - Daqu is a fermentative saccharification agent that is used to initiate
      fermentation in the production of Chinese liquor and vinegar. Different types of
      Daqu can be distinguished based on the maximum fermentation temperature, location
      of production, and raw materials used. We aimed to characterize and distinguish
      the different types of Daqu using a culture-independent cloning method. The
      lowest microbial diversity was found in Daqu produced at high-temperature.
      Principal component analysis (PCA) was used to compare the bacterial composition
      of Daqu from different regions (i.e., northern Daqu and southern Daqu).
      Staphylococcus gallinarum and Staphylococcus saprophyticus were found in southern
      Daqu, and were absent in northern Daqu. The fungi Saccharomycopsis fibuligera and
      Lichtheimia ramosa dominated in low/medium-temperature Daqu, whereas Thermomyces
      lanuginosus occurred in high-temperature Daqu. Our study identified potential
      biomarkers for the different types of Daqu, which can be useful for quality
      control and technology development of liquor or vinegar production. 

PMID- 25395234
TI  - We have met the enemy, and he or she is us.

PMID- 25395236
TI  - Reproducible simulations of realistic samples for next-generation sequencing
      studies using Variant Simulation Tools.
AB  - Computer simulations have been widely used to validate and evaluate the power of
      statistical methods for genetic epidemiological studies. Although a large number
      of simulation methods and software packages have been developed for genome-wide
      association studies, methodological and bioinformatics challenges have limited
      their applications in simulating datasets for whole-genome and whole-exome
      sequencing studies. With the development of more sophisticated statistical
      methods that make fuller use of available data and our knowledge of the human
      genome, there is a pressing need for genetic simulators that capture more
      features of empirical data (e.g., multiallele variants, indels, use of the
      Variant Call Format) and the human genome (e.g., functional annotations of
      genetic variants). This article introduces Variant Simulation Tools (VST), a
      module of Variant Tools for the simulation of genetic variants for sequencing
      based genetic epidemiological studies. Although multiple simulation engines are
      provided, the core of VST is a novel forward-time simulation engine that
      simulates real nucleotide sequences of the human genome using DNA mutation
      models, fine-scale recombination maps, and a selection model based on amino acid
      changes of translated protein sequences. The design of VST allows users to easily
      create and distribute simulation methods and simulated datasets for a variety of
      applications and encourages fair comparison between statistical methods through
      the use of existing or reproduced simulated datasets. 

PMID- 25395235
TI  - Integrative genomic analyses of a novel cytokine, interleukin-34 and its
      potential role in cancer prediction.
AB  - Interleukin-34 (IL-34) is a novel cytokine, which is composed of 222 amino acids
      and forms homodimers. It binds to the macrophage colony-stimulating factor (M
      CSF) receptor and plays an important role in innate immunity and inflammatory
      processes. In the present study, we identified the completed IL-34 gene in 25
      various mammalian genomes and found that IL-34 existed in all types of
      vertebrates, including fish, amphibians, birds and mammals. These species have a
      similar 7 exon/6 intron gene organization. The phylogenetic tree indicated that
      the IL-34 gene from the primate lineage, rodent lineage and teleost lineage form
      a species-specific cluster. It was found mammalian that IL-34 was under positive
      selection pressure with the identified positively selected site, 196Val. Fifty
      five functionally relevant single nucleotide polymorphisms (SNPs), including 32
      SNPs causing missense mutations, 3 exonic splicing enhancer SNPs and 20 SNPs
      causing nonsense mutations were identified from 2,141 available SNPs in the human
      IL-34 gene. IL-34 was expressed in various types of cancer, including blood,
      brain, breast, colorectal, eye, head and neck, lung, ovarian and skin cancer. A
      total of 5 out of 40 tests (1 blood cancer, 1 brain cancer, 1 colorectal cancer
      and 2 lung cancer) revealed an association between IL-34 gene expression and
      cancer prognosis. It was found that the association between the expression of IL
      34 and cancer prognosis varied in different types of cancer, even in the same
      types of cancer from different databases. This suggests that the function of IL
      34 in these tumors may be multidimensional. The upstream transcription factor 1
      (USF1), regulatory factor X-1 (RFX1), the Sp1 transcription factor 1 , POU class
      3 homeobox 2 (POU3F2) and forkhead box L1 (FOXL1) regulatory transcription factor
      binding sites were identified in the IL-34 gene upstream (promoter) region, which
      may be involved in the effects of IL-34 in tumors.

PMID- 25395237
TI  - Polarization entangled photons from quantum dots embedded in nanowires.
AB  - In this Letter, we present entanglement generated from a novel structure: a
      single InAsP quantum dot embedded in an InP nanowire. These structures can grow
      in a site-controlled way and exhibit high collection efficiency; we detect 0.5
      million biexciton counts per second coupled into a single mode fiber with a
      standard commercial avalanche photo diode. If we correct for the known setup
      losses and detector efficiency, we get an extraction efficiency of 15(3) %. For
      the measured polarization entanglement, we observe a fidelity of 0.76(2) to a
      reference maximally entangled state as well as a concurrence of 0.57(6). 

PMID- 25395238
TI  - Percutaneous cholecystostomy is an effective treatment option for acute calculous
      cholecystitis: a 10-year experience.
AB  - BACKGROUND: Percutaneous cholecystostomy (PC) can be used to treat patients with
      acute calculous cholecystitis (ACC) who are considered to be unfit for surgery.
      However, this procedure has been insufficiently investigated. This paper presents
      the results of a 10-year experience with this treatment modality. METHODS: A
      retrospective observational study of all consecutive patients treated with PC for
      ACC in the period from 1 May 2002 to 30 April 2012 was conducted. All data were
      collected from patients' medical records. RESULTS: A total of 278 patients were
      treated with PC for ACC. Of these, 13 (4.7%) died within 30 days, 28 (10.1%)
      underwent early laparoscopic cholecystectomy and three (1.1%) patients were lost
      from follow-up. Of the remaining 234 patients, 55 (23.5%) were readmitted for the
      recurrence of cholecystitis. In 128 (54.7%) patients, PC was the definitive
      treatment (median follow-up time: 5 years), whereas 51 (21.8%) patients were
      treated with elective laparoscopic cholecystectomy. The frequency of recurrence
      of cholecystitis in patients with contrast passage to the duodenum on
      cholangiography was lower than that in patients without contrast passage (21.1%
      versus 36.7%; P = 0.037). CONCLUSIONS: The present study, which is the largest
      ever conducted in this treatment area, supports the hypothesis that PC is an
      effective treatment modality for critically ill patients with ACC unfit for
      surgery and results in a low rate of 30-day mortality.

PMID- 25395239
TI  - Incidence trends of human papillomavirus-related head and neck cancer in Taiwan,
      1995-2009.
AB  - Recent studies suggested that human papillomavirus (HPV) is an emerging risk
      factor of head and neck cancer (HNC), particularly for oropharyngeal cancer.
      Studies from the West showed a rising trend of HPV-related HNC despite a decrease
      of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan
      has continued to rise. It is not clear whether the incidence trends of HPV
      related HNC in Taiwan have a similar pattern to those from countries with an
      overall decreasing incidence of HNC. This study examined the incidence trends of
      HPV-related and HPV-unrelated HNC in Taiwan using data from the Taiwan Cancer
      Registry. Our results showed that the incidence trends of HPV-related and HPV
      unrelated HNC in Taiwan both rose during 1995-2009. The incidence of HPV-related
      HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) =
      6.9, p < 0.0001) rose more rapidly than the incidence of HPV-unrelated HNC (10.4
      per 100,000 in 1995 to 21.7 in 2009, APC = 5.0, p < 0.0001). The rising trend of
      HPV-related HNC was particularly prominent for HNC occurring in tonsil (APC =
      8.2, p < 0.0001), in men (APC = 7.5, p < 0.0001), and in those aged between 40
      and 50 years (APC = 8.5, p < 0.0001). Although the overall incidence of HNC in
      Taiwan has continued to increase, the most rapid rise is in the HPV-related HNC.
      This suggests that similar to the Western world, HPV-related HNC is becoming an
      important public health issue in Taiwan. 

PMID- 25395240
TI  - Up-regulation of miR-21 and miR-23a Contributes to As2 O3 -induced hERG Channel
      Deficiency.
AB  - Arsenic trioxide (As2O3) is used to treat acute pro-myelocytic leukaemia.
      However, the cardiotoxicity of long QT syndrome restricts its clinical
      application. Previous studies showed that As2O3 can damage the hERG current via
      disturbing its trafficking to cellular membrane. Consistent with these findings,
      in this study, we reported that As2O3 inhibited hERG channel at both protein and
      mRNA levels and damaged hERG current but did not affect channel kinetics.
      Further, we demonstrated that As2O3 up-regulated miR-21 and miR-23a expression in
      hERG-HEK293 cells and neonatal cardiomyocytes. In addition, knock-down of miR-21
      by its specific antisense molecules AMO-21 was able to rescue Sp1 and hERG
      inhibition caused by As2O3. Consistently, phosphorylation of NF-kappaB, the
      upstream regulatory factor of miR-21, was significantly up-regulated by As2O3 .
      This finding revealed that regulation of the NF-kappaB-miR-21-Sp1 signalling
      pathway is a novel mechanism for As2O3-induced hERG inhibition. Meanwhile, the
      expression of Hsp90 and hERG was rescued by transfection with AMO-23a. And the
      hERG channel inhibition induced by As2O3 was rescued after being transfected with
      AMO-23a, which may be a molecular mechanism for the role of As2O3 in hERG
      trafficking deficiency. In brief, our study revealed that miR-21 and miR-23a are
      involved in As2O3-induced hERG deficiency at transcriptional and transportational
      levels. This discovery may provide a novel mechanism of As2O3-induced hERG
      channel deficiency, and these miRNAs may serve as potential therapeutic targets
      for the handling of As2O3 cardiotoxicity.

PMID- 25395241
TI  - Low HDL cholesterol is correlated to the acute ischemic stroke with diabetes
      mellitus.
AB  - BACKGROUND: To clarify the role of lipid composition in the occurrence of acute
      ischemic stroke (AIS) with diabetes mellitus (DM) and its influence factors.
      METHODS: Data was collected from the patients hospitalization in Affiliated Drum
      Tower Hospital of Nanjing University Medical School from October 2008 to May
      2012, which included AIS and non-AIS consist of transient ischemic attack (TIA)
      and Vertigo or dizzy. Lipid and other risk factors including blood glucose (BG),
      uric acid (UA), hypertension, DM and atrial fibrillation (AF) were investigated
      in relation to occurrence of AIS. RESULTS: The level of high density lipoprotein
      (HDL) cholesterol was decreased obviously in the DM group compared to the non-DM
      group and low level of HDL cholesterol was prevalent in the AIS patients with DM.
      logistic regression demonstrated that decreased HDL cholesterol was correlated to
      the AIS with DM, not all AIS, and the relative risk of ischemic stroke in low HDL
      cholesterol level group was 2.113 (95% CI = 1.191-3.749, P = 0.011) compared to
      the high level group. Furthermore, age has the obviously impact on it. HDL
      cholesterol was correlated to the AIS with DM just in the populations of aged ?70
      years (OR = 0.192, P = 0.000), low level of HDL cholesterol had more high risk of
      ischemic stroke than that in the high level group (OR = 6.818, P = 0.002).
      CONCLUSION: Decreased HDL cholesterol was correlated to the occurrence of AIS
      with DM, especially in the populations of aged ?70 years.

PMID- 25395242
TI  - Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like
      cells in vivo and in vitro.
AB  - Cell-based therapy is a potential alternative to liver transplantation. The goal
      of the present study was to examine the in vivo and in vitro hepatic
      differentiation potential of adipose tissue-derived mesenchymal stem cells (AT
      MSCs) and to explore its therapeutic use. AT-MSCs were isolated and cultured with
      hepatic differentiation medium. Bioactivity assays were used to study the
      properties of AT-MSCs. The morphology of differentiated AT-MSCs in serum-free
      hepatic differentiation medium changed into polygonal epithelial cells, while the
      morphology of AT-MSCs in a similar medium containing 2% fetal bovine serum
      remained unchanged. The differentiated cells cultured without serum showed
      hepatocyte-like cell morphology and hepatocyte-specific markers, including
      albumin (ALB) and alpha-fetoprotein. The bioactivity assays revealed that
      hepatocyte-like cells could take up low-density lipoprotein (LDL) and store
      glycogen. Furthermore, trichostatin A (TSA) enhanced ALB production and LDL
      uptake by the hepatocyte-like cells, analogous to the functions of human liver
      cells. ALB was detected in the livers of the CCl4-injured mice one month post
      transplantation. This suggested that transplantation of the human AT-MSCs could
      relieve the impairment of acute CCl4-injured livers in nude mice. This therefore
      implied that adipose tissue was a source of multipotent stem cells which had the
      potential to differentiate into mature, transplantable hepatocyte-like cells in
      vivo and in vitro. In addition, the present study determined that TSA was
      essential to promoting differentiation of human MSC towards functional hepatocyte
      like cells. The relief of liver injury following treatment with AT-MSCs suggested
      their potential as a novel therapeutic method for liver disorders or injury.

PMID- 25395243
TI  - Chemo-immunotherapy using saffron and its ingredients followed by E7-NT (gp96)
      DNA vaccine generates different anti-tumor effects against tumors expressing the
      E7 protein of human papillomavirus.
AB  - Saffron and its components have been suggested as promising candidates for cancer
      prevention. Carotenoids and monoterpene aldehydes are two potent ingredients of
      saffron. The goal of the current study was to investigate the anti-tumor effect
      of chemo-immunotherapy using saffron and its ingredients followed by E7-NT (gp96)
      DNA vaccine against tumors expressing the E7 protein of human papillomavirus. The
      in vitro cytotoxic and apoptotic effects of aqueous saffron extract and its
      components were evaluated in malignant TC-1 and non-malignant COS-7 cell lines.
      Then, multimodality treatments using E7-NT (gp96) DNA vaccine combined with
      saffron extract and its ingredients as well as single-modality treatments were
      tested for their efficacy in inhibiting large and bulky tumor growth. Saffron and
      its components exerted a considerable anti-tumor effect through prevention of
      cell growth and stimulation of programmed cell death. Furthermore, 100 % of mice
      treated with crocin were tumor-free, in contrast to DNA vaccine alone (~66.7 %)
      and DNA + crocin (~33.3 %) indicating the high potency of crocin as a
      chemotherapeutic agent. Interestingly, the multimodality treatment using DNA
      vaccine along with picrocrocin augmented the anti-tumor effects of picrocrocin.
      Thus, the combination of DNA vaccine with saffron extract and crocin at certain
      concentrations did not potentiate protective and therapeutic effects compared to
      mono-therapies for the control of TC-1 tumors. 

PMID- 25395244
TI  - MR elastography of prostate cancer: quantitative comparison with histopathology
      and repeatability of methods.
AB  - The purpose of this work was to assess trans-perineal prostate magnetic resonance
      elastography (MRE) for (1) repeatability in phantoms/volunteers and (2)
      diagnostic power as correlated with histopathology in prostate cancer patients.
      The three-dimensional (3D) displacement field was obtained using a fractionally
      encoded gradient echo sequence using a custom-made transducer. The repeatability
      of the method was assessed based on three repeat studies and by changing the
      driving frequency by 3% in studies on a phantom and six healthy volunteers.
      Subsequently, 11 patients were examined with MRE prior to radical prostatectomy.
      The areas under the receiver operating characteristic curves were calculated
      using a windowed voxel-to-voxel approach by comparing the 2D registered slides,
      masked with the Gleason score. For the repeatability study, the average
      intraclass correlation coefficient for elasticity images was 99% for repeat
      phantom studies, 98% for +/-6 Hz phantom studies, 95% for volunteer repeat
      studies with 2 min acquisition time, 82% for +/-2 Hz volunteer studies with 2 min
      acquisition time and 73% for repeat volunteer studies with 8 min acquisition
      time. For the patient study, the average elasticity was 8.2 +/- 1.7 kPa in the
      prostate capsule, 7.5 +/- 1.9 kPa in the peripheral zone (PZ), 9.7 +/- 3.0 kPa in
      the central gland (CG) and 9.0 +/- 3.4 kPa in the transition zone. In the patient
      study, cancerous tissue with Gleason score at least 3 + 3 was significantly (p <
      0.05) different from normal tissue in 10 out of 11 cases with tumors in the PZ,
      and 6 out of 9 cases with tumors in the CG. However, the overall case-averaged
      area under the curve was 0.72 in the PZ and 0.67 in the CG. Cancerous tissue was
      not always stiffer than normal tissue. The inversion algorithm was sensitive to
      (i) vibration amplitude and displacement nodes and (ii) misalignment of the 3D
      wave field due to subject movement.

PMID- 25395245
TI  - Initiating acute dialysis at earlier Acute Kidney Injury Network stage in
      critically ill patients without traditional indications does not improve outcome:
      a prospective cohort study.
AB  - AIM: Optimal timing for acute renal replacement therapy (ARRT) initiation in
      critically ill patients with acute kidney injury (AKI) is unclear. We aimed to
      evaluate outcomes in patients who initiated ARRT for traditional indications
      versus those who met Acute Kidney Injury Network (AKIN) criteria without
      traditional indications. METHODS: This was a single-centre prospective cohort
      study of medical and surgical intensive care patients with AKI. Traditional
      indications for ARRT initiation included: serum potassium >=6.0 mmol/L, serum
      urea >=30 mmol/L, arterial pH < 7.25, serum bicarbonate <10 mmol/L, acute
      pulmonary oedema, acute uraemic encephalopathy or pericarditis. In absence of
      these indications, ARRT was commenced if patients had (i) AKIN Stage 3 or (ii)
      AKIN Stage 1 or 2 with 'compelling' conditions. Primary outcomes were intensive
      care unit (ICU) and in-hospital mortality. RESULTS: ARRT was initiated in 140
      patients: traditional indications in 56 (40%); AKIN Stage 3 without traditional
      indications in 38 (27%); and AKIN Stage 1 or 2 with 'compelling' conditions in 46
      (33%) patients. Traditional indications at ARRT initiation was associated with
      increased in-hospital mortality (adjusted odds ratio (95% confidence interval),
      6.48 (1.54, 27.29)). In absence of traditional indications, earlier ARRT
      initiation, as defined by those with AKIN Stage 1 or 2, did not decrease ICU
      deaths (30.0% vs 18.8%, P = 0.30) or in-hospital mortality (50.0% vs 34.2%, P =
      0.15) compared with those who were started on ARRT for AKIN Stage 3. CONCLUSIONS:
      Presence of traditional indications at ARRT initiation was associated with
      greater mortality. Initiating dialysis at earlier AKIN stage did not improve
      survival in patients without traditional indications.

PMID- 25395246
TI  - Effect of scale on trait predictors of species responses to agriculture.
AB  - Species persistence in human-altered landscapes can depend on factors operating
      at multiple spatial scales. To understand anthropogenic impacts on biodiversity,
      it is useful to examine relationships between species traits and their responses
      to land-use change. A key knowledge gap concerns whether these relationships vary
      depending on the scale of response under consideration. We examined how local-
      and large-scale habitat variables influence the occupancy dynamics of a bird
      community in cloud forest zones in the Colombian Choco-Andes. Using data
      collected across a continuum of forest and agriculture, we examined which traits
      best predict species responses to local variation in farmland and which traits
      best predict species responses to isolation from contiguous forest. Global range
      size was a strong predictor of species responses to agriculture at both scales;
      widespread species were less likely to decline as local habitat cover decreased
      and as distance from forest increased. Habitat specialization was a strong
      predictor of species responses only at the local scale. Open-habitat species were
      particularly likely to increase as pasture increased, but they were relatively
      insensitive to variation in distance to forest. Foraging plasticity and flocking
      behavior were strong predictors of species responses to distance from forest, but
      not their responses to local habitat. Species with lower plasticity in foraging
      behaviors and obligate flock-following species were more likely to decline as
      distance from contiguous forest increased. For species exhibiting these latter
      traits, persistence in tropical landscapes may depend on the protection of larger
      contiguous blocks of forest, rather than the integration of smaller-scale
      woodland areas within farmland. Species listed as threatened or near threatened
      on the International Union for Conservation of Nature Red List were also more
      likely to decline in response to both local habitat quality and isolation from
      forest relative to least-concern species, underlining the importance of
      contiguous forests for threatened taxa.

PMID- 25395248
TI  - Three-dimensional mid-infrared tomographic imaging of endogenous and exogenous
      molecules in a single intact cell with subcellular resolution.
AB  - Microscopy in the mid-infrared spectral range provides detailed chemical
      information on a sample at moderate spatial resolution and is being used
      increasingly in the characterization of biological entities as challenging as
      single cells. However, a conventional cellular 2D imaging measurement is limited
      in its ability to associate specific compositional information to subcellular
      structures because of the interference from the complex topography of the sample.
      Herein we provide a method and protocols that overcome this challenge in which
      tilt-series infrared tomography is used with a standard benchtop infrared
      microscope. This approach gives access to the quantitative 3D distribution of
      molecular components based on the intrinsic contrast provided by the sample. We
      demonstrate the method by quantifying the distribution of an exogenous metal
      carbonyl complex throughout the cell and by reporting changes in its coordination
      sphere in different locations in the cell. 

PMID- 25395247
TI  - The challenge of treating orphan disease.
AB  - Uncommon or orphan diseases are less frequently addressed in mainstream medical
      journals and, as a consequence, their understanding and clinical recognition may
      rely on case series or anecdotal data with limited guidelines and management
      directions. The study of selected underrepresented autoimmune and allergy
      conditions is the subject of the present issue of Clinical Reviews in Allergy and
      Immunology to provide peculiar perspectives on common and rare themes. First,
      allergy remains a major concern for physicians worldwide despite the limited
      developments over the past years, particularly for antigens such as mite or
      Alternaria alternata, and due to the increasing incidence of drug
      hypersensitivity. Second, the female predominance of autoimmune diseases such as
      systemic sclerosis is well recognized but enigmatic, and a unifying hypothesis
      remains elusive. Third, the management of conditions triggered by infectious
      agents as in Guillain-Barre syndrome or mixed cryoglobulinemia is challenging,
      and clinical guidelines are needed in the setting of infections and autoimmunity.
      Fourth, gamma-delta T cells represent major players in innate immunity and are
      the subject of extensive studies in autoimmune diseases to provide new
      therapeutic targets for disease prevention or modulation in the near future.
      Ultimately, we acknowledge the major developments in the broad fields of
      rheumatology and immunology and expect that microbiota definition, epigenetics
      studies, and microRNA analysis will provide new exciting avenues toward the
      understanding and treatment of chronic and acute inflammation. 

PMID- 25395249
TI  - Does aging affect the outcome of percutaneous nephrolithotomy?
AB  - To investigate whether aging affects surgical outcomes by comparing the results
      of two patient groups undergoing PNL: those over 60 and those under 60. A
      retrospective screen was made for patients undergoing conventional PNL surgery
      for renal stones performed in two separate centers between 2010 and 2013. 520
      patients included were classified into age groups: patients aged 18-59 comprised
      Group-1 and those aged over 60 comprised Group-2. Those between 60-69 years
      (sexagenarian) were assigned to Group-2a; 70-79 years (septuagenarian) to Group
      2b; and 80-89 years (octogenarian) to Group-2c. Patients' demographic
      characteristics (accompanying comorbidities, ASA scores, body mass indices and
      stone size) and perioperative values (duration of surgery and hospital stay,
      success and complication rates) were compared between the groups. Mean stone size
      was similar in groups (30.1 +/- 15.5 vs. 31.5 +/- 15.4 mm, p = 0.379). The mean
      ASA value for the patients in Group-1 was 1.61; significantly lower than that in
      the other groups (p = 0.000). The level of accompanying comorbidities in Group-1
      was significantly lower than that of the other groups (p = 0.000). The mean
      duration of surgery, postoperative hematocrit drop, complication and success rate
      were statistically similar in Groups 1 and 2 (p = 0.860, p = 0.430, p = 0.7, and
      p = 0.66, respectively). The duration of hospital stay was significantly shorter
      in the patients in Group-1 compared to those in Group-2 (p = 0.008). In
      experienced hands, PNL can be safely and reliably performed in the treatment of
      renal stones in elderly patients. 

PMID- 25395250
TI  - Erratum to: A desirability function-based scoring scheme for selecting fragment
      like class A aminergic GPCR ligands.

PMID- 25395251
TI  - Acclimation to different environmental salinities induces molecular endocrine
      changes in the GH/IGF-I axis of juvenile gilthead sea bream (Sparus aurata L.).
AB  - To assess the role of the GH/IGF-I axis in osmotic acclimation of the gilthead
      seabream Sparus aurata, juvenile specimens were acclimated to four environmental
      salinities: hyposmotic (5 0/00), isosmotic (12 0/00) and hyperosmotic (40 and 55
      0/00). The full-length cDNAs for both pituitary adenylate cyclase-activating
      peptide (PACAP) and prepro-somatostatin-I (PSS-I), the precursor for mature
      somatostatin-I (SS-I), were cloned. Hypothalamic PACAP and PSS-I, hypophyseal
      growth hormone (GH) and prolactin (PRL), and hepatic insulin-like growth factor-I
      (IGF-I) mRNA expression levels were analyzed in the four rearing salinities
      tested. PACAP and IGF-I mRNA values increased significantly in response to both 5
      and 55 0/00 salinities, showing a U-shaped curve relationship with the basal
      level in the 40 0/00 group. Hypothalamic PSS-I expression increased strongly in
      the 55 0/00 environment. GH mRNA levels did not change in any of the tested
      environmental salinities. PRL mRNA maximum levels were encountered in the 5 and
      12 0/00 environments, but significantly down-regulated in the 40 0/00. Plasma
      cortisol levels significantly increased in the 40 0/00 environment. These results
      are discussed in relation to the well-known high adaptability of Sparus aurata to
      different environmental salinities and the role of the GH/IGF-I axis in this
      process.

PMID- 25395252
TI  - Electrocardiogram, heart movement and heart rate in the awake gecko (Hemidactylus
      mabouia).
AB  - The electrocardiogram (ECG) is the simplest and most effective non-invasive
      method to assess the electrical activity of the heart and to obtain information
      on the heart rate (HR) and rhythm. Because information on the HR of very small
      reptiles (body mass <10 g) is still scarce in the literature, in the present work
      we describe a procedure for recording the ECG in non-anesthetized geckos
      (Hemidactylus mabouia, Moreau de Jonnes, 1818) under different conditions, namely
      manual restraint (MR), spontaneous tonic immobility (TI), and in the non
      restrained condition (NR). In the gecko ECG, the P, QRS and T waves were clearly
      distinguishable. The HR was 2.83 +/- 0.02 Hz under MR, which was significantly
      greater (p < 0.001) than the HR under the TI (1.65 +/- 0.09 Hz) and NR (1.60 +/-
      0.10 Hz) conditions. Spontaneously beating isolated gecko hearts contracted at
      0.84 +/- 0.03 Hz. The in vitro beating rate was affected in a concentration
      dependent fashion by adrenoceptor stimulation with noradrenaline, as well as by
      the muscarinic cholinergic agonist carbachol, which produced significant positive
      and negative chronotropic effects, respectively (p < 0.001). To our knowledge,
      this is the first report on the ECG morphology and HR values in geckos,
      particularly under TI. The methodology and instrumentation developed here are
      useful for non-invasive in vivo physiological and pharmacological studies in
      small reptiles without the need of physical restraint or anesthesia.

PMID- 25395253
TI  - Synergistic effects of acute warming and low pH on cellular stress responses of
      the gilthead seabream Sparus aurata.
AB  - The present study assesses the resilience of the Mediterranean gilthead seabream
      (Sparus aurata) to acute warming and water acidification, using cellular
      indicators of systemic to molecular responses to various temperatures and CO2
      concentrations. Tissue metabolic capacity derived from enzyme measurements,
      citrate synthase, 3-hydroxyacyl CoA dehydrogenase (HOAD), as well as lactate
      dehydrogenase. Cellular stress and signaling responses were identified from
      expression patterns of Hsp70 and Hsp90, the phosphorylation of p38 MAPK, JNKs and
      ERKs, from protein ubiquitylation and finally from the levels of transcription
      factor Hif-1alpha as an indicator of systemic hypoxemia. Exposure to elevated CO2
      levels at temperatures higher than 24  degrees C generally caused an increase in
      fish mortality above the rate caused by warming alone, indicating effects of the
      two factors and a failure of acclimation and thus the limits of phenotypic
      plasticity to be reached. As a potential reason, tissue-dependent induction and
      stabilization of Hif-1alpha indicate hypoxemic conditions. Their exacerbation by
      enhanced CO2 levels is linked to the persistent expression of Hsp70 and Hsp90,
      oxidative stress and activation of MAPK and ubiquitin pathways. Antioxidant
      defence is enhanced by expression of catalase and glutathione reductase, however,
      leaving superoxide dismutase suppressed by elevated CO2 levels. On longer
      timescales in specimens surviving warming and CO2 exposures, various metabolic
      adjustments initiate a preference to oxidize lipid via HOAD for energy supply.
      These processes indicate significant acclimation up to a limit and a time-limited
      capacity to survive extreme conditions passively by exploiting mechanisms of
      cellular resilience. 

PMID- 25395254
TI  - Fluorescence quantum yield measurements of fluorescent proteins: a laboratory
      experiment for a biochemistry or molecular biophysics laboratory course.
AB  - Fluorescent proteins are commonly used in cell biology to assess where proteins
      are within a cell as a function of time and provide insight into intracellular
      protein function. However, the usefulness of a fluorescent protein depends
      directly on the quantum yield. The quantum yield relates the efficiency at which
      a fluorescent molecule converts absorbed photons into emitted photons and it is
      necessary to know for assessing what fluorescent protein is the most appropriate
      for a particular application. In this work, we have designed an upper-level,
      biochemistry laboratory experiment where students measure the fluorescence
      quantum yields of fluorescent proteins relative to a standard organic dye. Four
      fluorescent protein variants, enhanced cyan fluorescent protein (ECFP), enhanced
      green fluorescent protein (EGFP), mCitrine, and mCherry, were used, however the
      methods described are useful for the characterization of any fluorescent protein
      or could be expanded to fluorescent quantum yield measurements of organic dye
      molecules. The laboratory is designed as a guided inquiry project and takes two,
      4 hr laboratory periods. During the first day students design the experiment by
      selecting the excitation wavelength, choosing the standard, and determining the
      concentration needed for the quantum yield experiment that takes place in the
      second laboratory period. Overall, this laboratory provides students with a
      guided inquiry learning experience and introduces concepts of fluorescence
      biophysics into a biochemistry laboratory curriculum.

PMID- 25395255
TI  - Hearing loss in adult patients with Fabry disease treated with enzyme replacement
      therapy.
AB  - INTRODUCTION: Data on prevalence, natural history, and effect of enzyme
      replacement therapy (ERT) on hearing loss (HL) in Fabry disease (FD) are scarce.
      METHODS: This is a retrospective study with cross-sectional and longitudinal
      analyses. Low and high-frequency HL in the Dutch FD cohort was studied in four
      groups: classical and non-classical FD patients with or without ERT. To study
      effects of ERT, longitudinal data, corrected for age and gender according to ISO
      1999 guidelines, were analyzed with mixed models. RESULTS: In the cross-sectional
      analysis, 107 FD patients (41 males), median age 47.6 years (18.8-80.6) were
      analyzed. At baseline, i.e., before start of ERT, HL was present in 18 patients
      (16.8 %), of whom four had bilateral sensorineural HL. HL was more often present
      in patients with the classical phenotype than non-classical patients (p < 0.01).
      Likewise, males had more often HL than females. Compared to the general
      population, FD patients show a median HL of 8.2 dB at low frequencies (p < 0.01)
      and 29.5 dB at ultra-high frequencies (p < 0.01). Longitudinal analyses (n = 91)
      revealed that ERT treated patients show a similar rate of decline, not
      significantly different from healthy controls. CONCLUSION: Adult FD patients,
      especially classical affected males, show impaired hearing. Longitudinal analyses
      during ERT in these patients demonstrates a decline of HL similar to healthy
      controls, but HL present before initiation of therapy cannot be reversed. Whether
      early therapy can prevent hearing loss is unknown.

PMID- 25395256
TI  - Female host sex-biased parasitism with the rodent stomach nematode Mastophorus
      muris in wild bank voles (Myodes glareolus).
AB  - Abundance and prevalence of helminth infections often differ between host sexes,
      and are usually biased in favor of males. Relatively few cases of female-biased
      parasitism have been reported. We sampled bank voles in three woodland sites in
      N.E. Poland over 11 years at 3-4-year intervals, and assessed their parasite
      burdens. Prevalence and abundance of the stomach nematode Mastophorus muris were
      consistently higher among females. Among adult female bank voles from the two
      sites that showed the highest prevalence with M. muris, both prevalence and
      abundance were significantly higher in lactating bank voles, but not pregnant
      animals, and the effect of lactation was evident in both sites, in all four
      surveys, and in both age classes. Although the magnitude of the effect of
      lactation varied between years, it was not confounded by any significant
      interactions with other factors. We hypothesize that mature and reproductively
      active female bank voles are subject to higher exposure compared with males of
      similar age, as a consequence of the increased content of invertebrates in their
      diet, including the intermediate hosts of M. muris, required to meet the higher
      increased energy and protein demands of nursing litters throughout the summer
      months.

PMID- 25395257
TI  - The larvicidal activity of Agave sisalana against L4 larvae of Aedes aegypti is
      mediated by internal necrosis and inhibition of nitric oxide production.
AB  - Dengue is a viral disease that affects about 50 million people per year around
      the world. The aim of this study was to investigate the larvicidal activity of
      Agave sisalana crude extract in order to develop a new insecticide against Aedes
      aegypti. In larvicidal activity assays, fourth-stage Ae. aegypti larvae were
      exposed to different concentrations of A. sisalana crude extract for 3, 6, 12,
      and 24 h for determining the LC50. Next, we explored its cytotoxic activity by
      flow cytometry. Furthermore, histological alterations were confirmed by
      histopathological analysis, and the nitric oxide (NO) production by hemocytes was
      checked after different periods of exposure to A. sisalana crude extract. The
      LC50 was 4.5 +/- 0.07 mg/mL. In addition, flow cytometry revealed an increase of
      cellular necrosis (21 and 16.5 % after 12 and 24 h, respectively) in larvae that
      were exposed to A. sisalana crude extract. The histological analysis revealed
      cell lysis and destruction of the peritrophic membrane. Furthermore, there was a
      reduction in the concentration of NO in the hemolymph from larvae exposed to A.
      sisalana crude extract after 3, 6, and 24 h (5.3 +/- 4.3 vs. 22.7 +/- 5.2 MUM,
      4.3 +/- 5.5 vs. 25.4 +/- 6.6 MUM, and 6 +/- 1.7 vs. 37.1 +/- 7.8 MUM,
      respectively). Our findings show that A. sisalana crude extract constitutes an
      effective larvicidal agent against Ae. aegypti larvae due to its necrotizing
      activity in hemocytes and inhibition of the NO production.

PMID- 25395258
TI  - Hearing-aid use and its determinants in the UK National Health Service: a cross
      sectional study at the Royal Surrey County Hospital.
AB  - OBJECTIVES: The aim of this study was to investigate the rate of and factors
      contributing to non-adherence to hearing-aid use in the UK National Health
      Service. DESIGN: A cross-sectional postal questionnaire survey. STUDY SAMPLE: A
      questionnaire, including the International Outcome Inventory for Hearing Aids,
      was sent to all patients fitted with hearing aids at the Royal Surrey County
      Hospital between 2011 and 2012 (N = 1874). A total of 1023 questionnaires were
      completed and returned (response rate of 55%). RESULTS: A total of 29% of
      responders did not use their hearing aids on a regular basis (i.e. used them less
      than four hours per day). Non-regular use was more prevalent in new (40%) than in
      existing patients (11%). Factors that reduced the risk of non-regular use
      included bilateral versus unilateral amplification, and moderate or severe
      hearing loss in the better ear. 16% of responders fitted with bilateral
      amplification used only one of their hearing aids. CONCLUSIONS: The level of non
      regular use of hearing aids in NHS found in this study was comparable to those
      for other countries. Additional support might be needed for patients at a higher
      risk of non-regular use.

PMID- 25395259
TI  - Influence of musical training on sensitivity to temporal fine structure.
AB  - OBJECTIVE: The objective of this study was to extend the findings that temporal
      fine structure encoding is altered in musicians by examining sensitivity to
      temporal fine structure (TFS) in an alternative (non-Western) musician model that
      is rarely adopted--Indian classical music. DESIGN: The sensitivity to TFS was
      measured by the ability to discriminate two complex tones that differed in TFS
      but not in envelope repetition rate. STUDY SAMPLE: Sixteen South Indian classical
      (Carnatic) musicians and 28 non-musicians with normal hearing participated in
      this study. RESULTS: Musicians have significantly lower relative frequency shift
      at threshold in the TFS task compared to non-musicians. A significant negative
      correlation was observed between years of musical experience and relative
      frequency shift at threshold in the TFS task. Test-retest repeatability of
      thresholds in the TFS tasks was similar for both musicians and non-musicians.
      CONCLUSIONS: The enhanced performance of the Carnatic-trained musicians suggests
      that the musician advantage for frequency and harmonicity discrimination is not
      restricted to training in Western classical music, on which much of the previous
      research on musical training has narrowly focused. The perceptual judgments
      obtained from non-musicians were as reliable as those of musicians.

PMID- 25395260
TI  - The outcomes of kidney transplantation in hepatitis B surface antigen (HBsAg)
      negative recipients receiving graft from HBsAg-positive donors: a retrospective,
      propensity score-matched study.
AB  - The outcomes of kidney transplantation (KT) from hepatitis B surface antigen
      positive [HBsAg(+)] donors to HBsAg(-) recipients remain inconclusive, possibly
      due to substantial differences in methodological and statistical models, number
      of patients, follow-up duration, hepatitis B virus (HBV) prophylactic regimens
      and hepatitis B surface antibody (anti-HBs) levels. The present retrospective,
      longitudinal study (clinicaltrial.gov NCT02044588) using propensity score
      matching technique was conducted to compare outcomes of KT between HBsAg(-)
      recipients with anti-HBs titer above 100 mIU/mL undergoing KT from HBsAg(+)
      donors (n = 43) and HBsAg(-) donors (n = 86). During the median follow-up
      duration of 58.2 months (range 16.7-158.3 months), there were no significant
      differences in graft and patient survivals. No HBV-infective markers, including
      HBsAg, hepatitis B core antibody, hepatitis B extracellular antigen and HBV DNA
      quantitative test were detected in HBsAg(+) donor group. Renal pathology outcomes
      revealed comparable incidences of kidney allograft rejection while there were no
      incidences of HBV-associated glomerulonephritis and viral antigen staining.
      Recipients undergoing KT from HBsAg(+) donors with no HBV prophylaxis (n = 20)
      provided comparable outcomes with those treated with lamivudine alone (n = 21) or
      lamivudine in combination with HBV immunoglobulin (n = 2). In conclusion, KT
      without HBV prophylaxis from HBsAg(+) donors without hepatitis B viremia to
      HBsAg(-) recipients with anti-HBs titer above 100 mIU/mL provides excellent graft
      and patient survivals without evidence of HBV transmission. 

PMID- 25395261
TI  - Stable suppression of myostatin gene expression in goat fetal fibroblast cells by
      lentiviral vector-mediated RNAi.
AB  - Myostatin (MSTN) is a secreted growth factor that negatively regulates skeletal
      muscle mass, and therefore, strategies to block myostatin-signaling pathway have
      been extensively pursued to increase the muscle mass in livestock. Here, we
      report a lentiviral vector-based delivery of shRNA to disrupt myostatin
      expression into goat fetal fibroblasts (GFFs) that were commonly used as
      karyoplast donors in somatic-cell nuclear transfer (SCNT) studies. Sh-RNA
      positive cells were screened by puromycin selection. Using real-time polymerase
      chain reaction (PCR), we demonstrated efficient knockdown of endogenous myostatin
      mRNA with 64% down-regulation in sh2 shRNA-treated GFF cells compared to GFF
      cells treated by control lentivirus without shRNA. Moreover, we have also
      demonstrated both the induction of interferon response and the expression of
      genes regulating myogenesis in GFF cells. The results indicate that myostatin
      targeting siRNA produced endogenously could efficiently down-regulate myostatin
      expression. Therefore, targeted knockdown of the MSTN gene using lentivirus
      mediated shRNA transgenics would facilitate customized cell engineering, allowing
      potential use in the establishment of stable cell lines to produce genetically
      engineered animals.

PMID- 25395263
TI  - Use of logistic regression to combine two causality criteria for signal detection
      in vaccine spontaneous report data.
AB  - PURPOSE: We evaluated the use of logistic regression to model the probabilities
      of spontaneously reported vaccine-event pairs being adverse reactions following
      immunization (ARFI), using disproportionality and unexpectedness of time-to-onset
      (TTO) distributions as predictive variables and the presence of events in the
      global product information as a dependent variable. METHODS: We used spontaneous
      reports of adverse events from eight vaccines and their labels as proxies for
      ARFIs. Three logistic regressions were built to predict ARFIs based on different
      combinations of the proportional reporting ratio (PRR; disproportionality
      measure) and two Kolmogorov-Smirnov (KS) tests ('between vaccines' and the
      'between events') of TTO distribution: model 1, using the PRR estimate and its
      95% lower confidence interval (CI) limit; model 2, using the p values of the two
      KS tests; and model 3, using the PRR (point estimate and lower CI limit) and both
      KS tests. The performance of the regressions (model fit statistics, calibration,
      and discrimination) was measured on 100 bootstrap samples. RESULTS: Model 3,
      using two quantified causality criteria, provided the best performance for all
      measures. The p value of the 'between vaccines' KS test was the most significant
      predictive factor. Model 1 had the worst performance. CONCLUSIONS: Logistic
      regression allows estimation of the probability of a vaccine-event pair being an
      ARFI using two causality criteria at the population level assessed in spontaneous
      report data: the strength of association (disproportionality measure) and
      temporality (TTO distribution tests). Logistic regression combines and weights
      these causality criteria based on their respective ability to predict known
      safety issues.

PMID- 25395264
TI  - Effect of chronic continual- and intermittent hypoxia-induced systemic
      inflammation on the cardiovascular system in rats.
AB  - PURPOSE: Obstructive sleep apnea syndrome (OSAS) has been recognized as an
      important risk factor for cardiovascular morbidity and mortality. However, the
      underlying mechanisms are poorly understood. Present study aimed to investigate
      the role of NF-kappaB-dependent inflammation pathways in pathophysiological
      responses of cardiovascular system in OSAS. METHODS: Thirty male specific
      pathogen-free (SPF) Sprague-Dawley rats were randomly assigned to normoxia (N)
      group, continual hypoxia (CH) group, and intermittent hypoxia (IH) group (n = 10)
      and were exposed to N (21% O2), CH (8% O2), or IH (6-11% O2 for 10 s and 21% O2
      for 80 s in every 90 s) for 8 h/day for 35 days. The hemodynamic and
      pathomorphologic effects of IH and CH exposure were investigated as well as the
      expression of NF-kappaB-dependent inflammation factors. RESULTS: Chronic IH or CH
      significantly increased mean pulmonary arterial pressure (mPAP) in rats, while no
      significant changes occurred in mean carotid arterial pressure (mCAP). The ratio
      of right ventricle (RV) to left ventricle (LV) + septum (S) was significantly
      increased by both IH and CH, suggesting RV hypertrophy was induced by IH or CH.
      Elastic fiber staining showed an irregular pattern of elastic fiber distribution
      after hypoxia, and aortic tunica media thickness was increased. Both chronic IH
      and CH upregulated the expressions of transcription factor NF-kappaB and related
      pro-inflammatory cytokines and adhesion molecules. CONCLUSIONS: The current study
      expands our understanding that both IH and CH could activate the expression of NF
      kappaB and related inflammatory factors as well as cause pathophysiologic damage
      to the cardiovascular system in OSAS. All these results provide further support
      to an emerging hypothesis that activation of NF-kappaB-dependent inflammation may
      play a central role in the pathophysiology of cardiovascular dysfunction in OSAS.

PMID- 25395265
TI  - Quantitative EMG criteria for diagnosing idiopathic REM sleep behavior disorder.
AB  - PURPOSE: The purpose of this study is to determine the diagnostic cutoff for the
      proportion of rapid eye movement (REM) sleep with tonic and phasic activities of
      the submentalis muscle activity that can be used to diagnose REM sleep behavior
      disorder (RBD). METHODS: Seventeen patients clinically diagnosed as idiopathic
      RBD and 15 age- and gender-matched controls were studied. Surface
      electromyography was recorded from the submentalis muscle, and two sleep
      technologists manually identified epochs with tonic and phasic activities during
      REM sleep. Receiver operating characteristic (ROC) curves were constructed to
      find the optimal cutoff values for diagnosing RBD using the proportion of REM
      sleep with tonic and phasic activities of the submentalis muscle. Cohen's kappa
      coefficient was calculated to evaluate interrater reliability. RESULTS: The
      cutoff value with the optimal sensitivity and specificity was 6.5% for the
      proportion of REM sleep with tonic activity (sensitivity, 94.1%; specificity,
      93.3%; area under the ROC curve, 0.976) and 9.5% for the proportion of REM sleep
      with phasic activity (sensitivity, 94.1%; specificity, 93.3%; area under the ROC
      curve, 0.992). The cutoff value required to achieve a specificity of 100% was
      8.9% for tonic activity and 11.1% for phasic activity. Cohen's kappa coefficient
      between two scorers was 0.96 (95% confidence interval, 0.95-0.97) and 0.95 (95%
      confidence interval, 0.94-0.95) for tonic and phasic activities, respectively
      (both p < 0.001). CONCLUSIONS: Identifying periods of tonic and phasic activities
      of the submentalis muscle during REM sleep is useful to discriminate patients
      with idiopathic RBD from controls.

PMID- 25395266
TI  - Non-invasive fat reduction of the flanks using a new cryolipolysis applicator and
      overlapping, two-cycle treatments.
AB  - BACKGROUND AND OBJECTIVES: A sharply contoured cryolipolysis vacuum applicator
      was developed to improve fit and tissue draw in the abdomen and flanks to better
      accommodate a range of body types and a variety of treatment sites. This study
      was carried out to evaluate the safety and efficacy of the new applicator for
      treatment of flank fat ("love handles"). STUDY DESIGN/MATERIALS AND METHODS: A
      cryolipolysis vacuum applicator with a sharply contoured cup and curved cooling
      plates was used to treat 20 flanks. Two treatment cycles were delivered
      sequentially to each flank (60-minute cycle at a Cooling Intensity Factor of
      41.6). Efficacy was evaluated 12 weeks post-treatment by physicians performing
      blinded, independent review of clinical photographs. Safety was assessed by the
      treating physician monitoring subjects for side effects and adverse events.
      RESULTS: Four blinded, independent physician reviewers properly identified the
      pre- and post-treatment photographs 94.4% of the time. Improvement was scored
      from 0 (none) to 10 (complete) and showed an average 4.3 point (43%) improvement.
      Side-effects were limited to erythema, edema, bruising, and numbness or tingling
      at the treatment site, and resolved without treatment. CONCLUSIONS: Multiple
      treatment cycles from a new improved-fit cryolipolysis applicator are safe and
      effective for reduction of flank fat bulges. A high degree of improvement was
      reported by blinded, physician evaluation of standardized photographs.

PMID- 25395267
TI  - Maternal hypertensive disorders, antihypertensive medication use, and the risk of
      birth defects: a case-control study.
AB  - OBJECTIVE: To study previously identified associations between specific maternal
      hypertensive disorders and/or prenatal exposure to antihypertensive medication
      and birth defects. DESIGN: Case-control study. SETTING: Slone Birth Defects
      Study, 1998-2010. POPULATION: A total of 5568 cases with birth defects and 7253
      liveborn infants without malformations as controls. METHODS: Adjusted odds ratios
      (aORs) for birth defects associated with prenatal exposure to maternal
      hypertensive disorders and/or antihypertensive medication were calculated using
      multivariable logistic regression analyses. MAIN OUTCOME MEASURES: Specific birth
      defects previously linked to maternal hypertension or antihypertensive medication
      use during pregnancy. RESULTS: Non-pharmacologically managed chronic hypertension
      was associated with a three-fold risk of oesophageal atresia (95% CI 1.2-8.3),
      and pre-eclampsia superimposed on non-pharmacologically managed chronic
      hypertension was associated with ventricular septal defects (aOR 3.9, 95% CI 1.3
      11.7) and atrial septal defects (aOR 6.5, 95% CI 1.8-23.7). For chronic
      hypertension that was pharmacologically treated early in pregnancy, increased
      risks were observed for first-degree hypospadias (aOR 2.9, 95% CI 1.1-7.4). Non
      pharmacologically managed pre-eclampsia was related to second-/third-degree
      hypospadias and ventricular septal defects. Pharmacological treatment for
      gestational hypertension was associated with a number of congenital heart
      defects. CONCLUSIONS: Our results confirm some, but not all, previously
      identified associations between pharmacologically treated and non
      pharmacologically managed hypertensive disorders and specific birth defects. They
      support the hypothesis that physiological changes early in pregnancy that
      manifest in gestational hypertension and pre-eclampsia may play a role in the
      aetiology of major birth defects, including congenital heart defects and
      hypospadias.

PMID- 25395268
TI  - The role of Chlamydia pneumoniae in the etiology of keratoconjunctivitis sicca
      (KCS).
AB  - AIM: The authors aimed to show the possible relationship between
      keratoconjunctivitis sicca (KCS) and Chlamydia pneumonia from the point of view
      of clinical and microbiological diagnostics. MATERIAL AND METHODS: 94 adult
      patients were treated for follicular conjunctivitis with symptoms of KCS with
      possible Chlamydia pneumoniae etiology. The diagnosis of a chlamydial infection
      is based on the serological positivity of chlamydia antibodies and is further
      based on the antigen positivity in conjunctival imprint preparations. Patients
      were treated with azithromycin for a period of 12 days. RESULTS: The reciprocal
      relationship between chlamydial infection and ocular symptoms was proved at 21
      patients (22%). Ninety% of patients showed positive anti-Chlamydia pneumoniae IgA
      and/or IgM with positivity in 80%, including anti-LSP IgA and/or IgM antibodies.
      This finding was in correlation with the medium to strongly positive finding of
      anti-cHSP60 IgG. In two patients, this infection was confirmed by the positivity
      of Chlamydia pneumoniae DNA in peripheral leucocytes. The test group (100 healthy
      persons) showed 69% negative finding of anti-Chlamydia pneumoniae antibodies or
      only positive anamnestic antibodies (IgG) and 31% positive antibodies IgA or IgM
      without clinical sings. CONCLUSION: This study indicated the possible
      relationship between KCS and Chlamydia pneumoniae in the course of simultaneous
      clinical signs of follicular conjunctivitis. KCS is a consequence of the action
      of local infection at the surface of the conjunctiva. It also indicated the
      necessity of simultaneous evaluation of microbiological findings and the clinical
      picture in consideration of overall antibiotic treatment in view of the high
      antibody background of Chlamydia pneumoniae in the adult population in the Czech
      Republic. The authors aimed to show the possible relationship between the
      keratoconjunctivitis sicca and Chlamydia pneumoniae based on results of the two
      studies. Some patents on conjunctivitis are also briefly described in this
      article.

PMID- 25395269
TI  - Biosimilar products are not bioidentical.

PMID- 25395270
TI  - Hierarchical Bayesian model for rare variant association analysis integrating
      genotype uncertainty in human sequence data.
AB  - Next-generation sequencing (NGS) has led to the study of rare genetic variants,
      which possibly explain the missing heritability for complex diseases. Most
      existing methods for rare variant (RV) association detection do not account for
      the common presence of sequencing errors in NGS data. The errors can largely
      affect the power and perturb the accuracy of association tests due to rare
      observations of minor alleles. We developed a hierarchical Bayesian approach to
      estimate the association between RVs and complex diseases. Our integrated
      framework combines the misclassification probability with shrinkage-based
      Bayesian variable selection. It allows for flexibility in handling neutral and
      protective RVs with measurement error, and is robust enough for detecting causal
      RVs with a wide spectrum of minor allele frequency (MAF). Imputation uncertainty
      and MAF are incorporated into the integrated framework to achieve the optimal
      statistical power. We demonstrate that sequencing error does significantly affect
      the findings, and our proposed model can take advantage of it to improve
      statistical power in both simulated and real data. We further show that our model
      outperforms existing methods, such as sequence kernel association test (SKAT).
      Finally, we illustrate the behavior of the proposed method using a Finnish low
      density lipoprotein cholesterol study, and show that it identifies an RV known as
      FH North Karelia in LDLR gene with three carriers in 1,155 individuals, which is
      missed by both SKAT and Granvil. 

PMID- 25395271
TI  - Incidence of hospital readmission in patients diagnosed with DVT and PE: clinical
      burden of recurrent events.
AB  - BACKGROUND: Venous thromboembolism (VTE), which comprises deep-vein thrombosis
      (DVT) and pulmonary embolism (PE), is associated with significant morbidity and
      mortality and represents a considerable economic burden to the US healthcare
      system. Although it is well established that patients with an initial VTE are at
      increased risk for recurrent VTE, limited data exist on the clinical burden of a
      secondary DVT or PE event. The objective of this retrospective observational
      study was to conduct an epidemiologic evaluation, from a hospital perspective, of
      patients with an initial DVT or PE who experienced a recurrent event
      postdischarge requiring hospital readmission. METHODS: Hospital claims containing
      DVT or PE as a primary diagnosis for hospitalisation during the period October
      2009 to April 2013 were identified by retrospective analysis using the MarketScan
      database. The time to hospital readmission for DVT or PE was assessed using the
      MarketScan Treatment Pathways tool. RESULTS: Of 214,901 patient admissions
      identified with a diagnosis of DVT or PE at hospital admission, approximately 4%
      were subsequently readmitted to the hospital with a diagnosis of PE (8217) or DVT
      (9138). Of all readmitted patients with a diagnosis of DVT on initial admission,
      66% were rehospitalised with a diagnosis of DVT, and 34% were rehospitalised with
      a diagnosis of PE. Of all readmitted patients with a diagnosis of PE on initial
      admission, 63% were rehospitalised with a diagnosis of PE and 37% with a
      diagnosis of DVT. Of all hospital readmissions with a diagnosis of PE or DVT, 62%
      and 58% occurred within the first 30 days following an initial PE or DVT event,
      respectively. CONCLUSIONS: The burden of DVT or PE is large, not only because of
      the initial hospitalisation event but also because of the high number of hospital
      readmissions, more than half of which occur within 30 days.

PMID- 25395272
TI  - Anterior translation and rotational stability of anterior cruciate ligament
      deficient knees during walking: speed and turning direction.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) rupture is one of the most common
      injuries associated with the knee. After ACL injury, knee joint stability can be
      altered, resulting in abnormal loading during functional activities. Since ACL
      deficient (ACLD) knees are also vulnerable to translational and rotational
      instability, patients need to be wary of certain motions encountered in daily
      life. The present study investigated the effect of walking speed and pivoting
      directional change during gait on knee joint kinematics of ACLD knees. We
      hypothesized that faster walking and crossover turning would induce severe
      kinematic changes. METHODS: Thirty-five patients (22 males and 13 females) having
      a unilateral isolated subacute ACLD knee (from 1 to 3 months after injury) and
      contralateral intact (CLI) knee participated in this study. Spatiotemporal
      parameters, three-dimensional (3D) knee joint angles, and anterior-posterior (AP)
      translation were obtained by a 3D high-speed motion-capturing system. The CLI
      knee of each patient served as the control. The calculated AP stability and knee
      joint angles were used to test the research hypothesis. Mixed two-way repeated
      measures analysis of variance was performed to clarify the effects of walking
      speed and pivoting direction with a significance of 0.05. When a significance of
      mean comparison was detected, a post hoc test was performed. RESULTS: Significant
      and consistent increased AP translation of the tibia relative to the femur at the
      whole stance phase of the gait cycle was evident in ACLD knees compared to CLI
      knees for normal and faster (20 % greater than normal) walking speeds. Faster
      walking speed did not induce significantly more anterior location of the tibia.
      In addition, ACLD knees were significantly less extended than CLI knees during a
      large portion of midstance. Although there was a consistent varus offset between
      the curves of ACLD and CLI knees, the difference did not reach statistical
      significance during the stance phase. Also, ACLD knees did not show any
      significant difference in tibial rotation compared to CLI knees during the entire
      stance phase of the gait cycle. For pivoting turns, ACLD knees showed
      significantly less extended and varus offset than CLI knees only during the
      cutting turn. ACLD knees exhibited less tibial internal rotation during the
      crossover turn and less tibial external rotation during the cutting turn than CLI
      knees. CONCLUSIONS: In ACLD knees, the tibia tended to shift more anteriorly and
      changed with less extension at walking. However, faster walking speed did not
      induce any significant difference compared with normal-speed walking. In
      addition, ACLD knees displayed kinematic changes during pivoting, but not the
      crossover turn.

PMID- 25395273
TI  - Net endogenous acid production and mortality in NHANES III.
AB  - AIM: Low serum bicarbonate is a strong mortality risk factor in people with low
      estimated glomerular filtration rate (eGFR). It may also raise mortality risk in
      people with normal eGFR. This study investigated whether higher net endogenous
      acid production (NEAP), an estimate of net dietary acid intake and a risk factor
      for chronic kidney disease (CKD) progression, associates with higher mortality in
      people with and without low eGFR. METHODS: NEAP was calculated among adult
      participants in the Third National Health and Nutrition Examination Survey as 
      10.2 + 54.5 x (protein intake in grams per day/potassium intake in
      milliequivalent per day). Cox models were performed in the (i) total population
      and (ii) low eGFR and (iii) normal eGFR subgroups using the lowest NEAP quartile
      as the reference. RESULTS: Sixteen thousand nine hundred six participants were
      included in the analysis. The mortality hazard ratios (95% confidence interval)
      for the highest NEAP quartile (72-145 mEq/day) were: (i) 0.75 (0.62-0.90) in the
      total population; (ii) 0.77 (0.51-1.17) in the low eGFR subgroup; and (iii) 0.75
      (0.61-0.93) in the normal eGFR subgroup after adjusting for demographics, serum
      bicarbonate, eGFR, albuminuria and comorbidities. The mortality hazard ratios in
      the second and third NEAP quartiles were similar to the lowest (reference) NEAP
      quartile in the total population and low and normal eGFR subgroups. CONCLUSIONS:
      Higher NEAP is not associated with higher mortality in people with low or normal
      eGFR. Future studies should consider the effect of modifying dietary acid and
      alkali intake on mortality and CKD progression in people with reduced eGFR.

PMID- 25395274
TI  - Association between adult weight gain and colorectal cancer: a dose-response meta
      analysis of observational studies.
AB  - This study investigated the association between adult weight gain and risk of
      colorectal cancer (CRC). Using terms related to weight gain and CRC, we searched
      PubMed, Embase and Web of Science for relevant studies published before June
      2014. Two evaluators independently selected studies according to the selection
      criteria, and eight studies were included (three case-control and five cohort
      studies). Summary estimates were obtained using fixed- or random-effects models.
      The relative risk (RR) of the association between adult weight gain and CRC was
      1.25 (95% confidence interval [CI], 1.10-1.43); the RR was 1.30 (95% CI, 1.14
      1.49) for colon cancer (CC) and 1.27 (95% CI, 1.02-1.58) for rectal cancer (RC)
      for the highest versus lowest category. For every 5-kg increase in adult weight,
      the risk increased by 5% (RR, 1.05; 95% CI, 1.02-1.09) for CRC, 6% (RR, 1.06; 95%
      CI, 1.02-1.11) for CC and 6% (RR, 1.06; 95% CI, 1.03-1.08) for RC. The subgroup
      analyses showed a positive association between adult weight gain and risk of CRC
      only in men, and the RR was 1.65 (95% CI, 1.42-1.92) for the highest versus
      lowest category of adult weight gain and 1.10 (95% CI, 1.06-1.15) for a 5-kg
      increase in adult weight. In conclusion, there is evidence that adult weight gain
      is associated with an increased risk of CRC. However, the positive association
      between adult weight gain and risk of CRC is stronger among men than among women.

PMID- 25395275
TI  - Taurine induces the apoptosis of breast cancer cells by regulating apoptosis
      related proteins of mitochondria.
AB  - Taurine (Tau), the most abundant free amino acid in humans has numerous potential
      health benefits through its antioxidant and anti-inflammatory properties.
      However, limited studies have assessed its effect on tumors and the antitumor
      mechanism remains unknown. The present study investigated the cellular and
      molecular changes induced by Tau, leading to the induction of apoptosis in human
      breast cancer cell lines MCF-7 and MDA-MB-231. MCF-7 is p53 proficient (p53+/+)
      and MDA-MB-231 is a p53 null mutant (p53-/-). Cell proliferation and viability
      were assessed by MTT. Flow cytometry and hoechst33342 fluorescent staining were
      employed to detect apoptosis. Spectrophotometry was used to detect caspase-3
      activity. Reverse transcription-polymerase chain reaction and western blot
      analysis were used to detect the levels of mRNA and proteins of p53-upregulated
      modulator of apoptosis (PUMA), Bax and Bcl-2. Finally, the affect of Tau on the
      growth of MDA-MB-231-cell-nude mice xenografts was examined. In the study, Tau
      inhibited growth and induced apoptosis of the two cell lines in a concentration-
      and time-dependent manner. Notably, the inhibitory effect of Tau on p53-/- cancer
      cells was clearly significant compared to the p53+/+ cancer cells. Further
      studies showed that Tau promoted apoptosis in human breast cancer cells and
      inhibited the growth of tumor in nude mice by inducing the expression of PUMA,
      which further up- and downregulated the expression of Bax and Bcl-2 protein,
      giving rise to increased activation of caspase-3. Collectively, these results
      indicate that Tau is a potent candidate for the chemotherapy of breast cancer
      through increasing the PUMA expression independent of p53 status.

PMID- 25395276
TI  - 11,11,12,12-Tetracyano-4,5-pyrenoquinodimethanes: air-stable push-pull o
      quinodimethanes with S2 fluorescence.
AB  - The synthesis and properties of 11,11,12,12-tetracyano-4,5-pyrenoquinodimethanes
      (4,5-TCNPs), a new family of isolable and air-stable o-quinodimethanes, are
      reported. The ortho disposition of the dicyanomethane substituents strongly
      polarizes the pyrene framework to promote broad and intense intramolecular charge
      transfer transitions. In addition, spectroscopic studies reveal that 4,5-TCNPs
      violate Kasha's rule and emit from the S2 level. 

PMID- 25395277
TI  - Stepwise halide-triggered double and triple catenation of self-assembled
      coordination cages.
AB  - A simple self-assembled [Pd2 L4 ] coordination cage consisting of four carbazole
      based ligands was found to dimerize into the interpenetrated double cage [3 X@Pd4
      L8 ] upon the addition of 1.5 equivalents of halide anions (X=Cl(-) , Br(-) ).
      The halide anions serve as templates, as they are sandwiched by four Pd(II)
      cations and occupy the three pockets of the entangled cage structure. The
      subsequent addition of larger amounts of the same halide triggers another
      structural conversion, now yielding a triply catenated link structure in which
      each Pd(II) node is trans-coordinated by two pyridine donors and two halide
      ligands. This simple system demonstrates how molecular complexity can increase
      upon a gradual change of the relative concentrations of reaction partners that
      are able to serve different structural roles.

PMID- 25395278
TI  - A cost-benefit/cost-effectiveness analysis of an unsanctioned supervised smoking
      facility in the Downtown Eastside of Vancouver, Canada.
AB  - BACKGROUND: Smoking crack involves the risk of transmitting diseases such as HIV
      and hepatitis C (HCV). The current study determines whether the formerly
      unsanctioned supervised smoking facility (SSF)-operated by the grassroot
      organization, Vancouver Area Network of Drug Users (VANDU) for the last few years
      costs less than the costs incurred for health-care services as a direct
      consequence of not having such a program in Vancouver, Canada. METHODS: The data
      pertaining to the attendance at the SSF was gathered in 2012-2013 by VANDU. By
      relying on this data, a mathematical model was employed to estimate the number of
      HCV infections prevented by the former facility in Vancouver's Downtown Eastside
      (DTES). RESULTS: The DTES SSF's benefit-cost ratio was conservatively estimated
      at 12.1:1 due to its low operating cost. The study used 70% and 90% initial pipe
      sharing rates for sensitivity analysis. At 80% sharing rate, the marginal HCV
      cases prevented were determined to be 55 cases. Moreover, at 80% sharing rate,
      the marginal cost-effectiveness ratio ranges from $1,705 to $97,203. The results
      from both the baseline and sensitivity analysis demonstrated that the
      establishment of the SSF by VANDU on average had annually saved CAD$1.8 million
      dollars in taxpayer's money. CONCLUSIONS: Funding SSFs in Vancouver is an
      efficient and effective use of financial resources in the public health domain;
      therefore, Vancouver Coastal Health should actively participate in their
      establishment in order to reduce HCV and other blood-borne infections such as HIV
      within the non-injecting drug users.

PMID- 25395280
TI  - Serum 25-Hydroxyvitamin D and Parathyroid Hormone Levels in Non-Lactating Women
      with Post-Partum Thyroiditis: The Effect of L-Thyroxine Treatment.
AB  - Vitamin D deficiency seems to be implicated in the onset and progression of some
      autoimmune disorders. No previous study has investigated vitamin D homeostasis in
      post-partum thyroiditis. We compared 25-hydroxyvitamin D and parathyroid hormone
      (PTH) levels between four groups of non-lactating women who gave birth within 12
      months before the beginning of the study: hypothyroid women with post-partum
      thyroiditis (group A; n = 14), euthyroid females with post-partum thyroiditis
      (group B; n = 14), women with non-autoimmune hypothyroidism (group C; n = 16) and
      healthy euthyroid females without thyroid autoimmunity (group D; n = 15). In the
      second part of the study, groups A and C were treated for 6 months with L
      thyroxine. Serum levels of 25-hydroxyvitamin D were lower, while PTH higher in
      patients with post-partum thyroiditis than in patients without thyroid
      autoimmunity. They were also lower (25-hydroxyvitamin D) or higher (PTH) in group
      A than in group B, as well as in group C in comparison with group D. L-thyroxine
      treatment increased 25-hydroxyvitamin D and reduced PTH levels only in
      hypothyroid women with post-partum thyroiditis. Baseline levels of 25
      hydroxyvitamin D correlated with thyroid antibody titres, thyroid function and
      circulating PTH levels, while the effect of L-thyroxine on serum levels of this
      vitamin correlated with the changes in thyroid antibody titres and PTH levels.
      The results of our study suggest the association of vitamin D status with post
      partum thyroiditis and L-thyroxine treatment of this disorder.

PMID- 25395281
TI  - Central pontine myelinolysis.

PMID- 25395282
TI  - Primum non nocere: do we harm stage I testicular cancer patients less by applying
      adjuvant chemotherapy than by failing to present this option?

PMID- 25395283
TI  - Randomized, phase III trial of figitumumab in combination with erlotinib versus
      erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer.
AB  - BACKGROUND: Figitumumab (CP-751,871) is a fully human IgG2 monoclonal antibody
      that inhibits the insulin-like growth factor 1 receptor. This multicenter,
      randomized, phase III study investigated the efficacy of figitumumab plus
      erlotinib compared with erlotinib alone in patients with pretreated, nonsmall
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (stage IIIB/IV or
      recurrent disease with nonadenocarcinoma histology) who had previously received
      at least one platinum-based regimen were randomized to receive open-label
      figitumumab (20 mg/kg) plus erlotinib 150 mg/day or erlotinib alone every 3
      weeks. The primary end point was overall survival (OS). RESULTS: Of 583 patients
      randomized, 579 received treatment. The study was closed early by an independent
      data safety monitoring committee due to results crossing the prespecified
      futility boundary. At the final analysis, median OS was 5.7 months for
      figitumumab plus erlotinib and 6.2 months for erlotinib alone [hazard ratio (HR)
      1.09; 95% confidence interval (CI) 0.91-1.31; P = 0.35]. Median progression-free
      survival was 2.1 months for figitumumab plus erlotinib and 2.6 months for
      erlotinib alone (HR 1.08; 95% CI 0.90-1.29; P = 0.43). Treatment-related nonfatal
      serious adverse events occurred in 18% and 5% of patients in the figitumumab arm
      or erlotinib alone arm, respectively. There were nine treatment-related deaths
      (three related to both drugs, four related to erlotinib alone and two related to
      figitumumab). CONCLUSIONS: The addition of figitumumab to erlotinib did not
      improve OS in patients with advanced, pretreated, nonadenocarcinoma NSCLC.
      Clinical development of figitumumab has been discontinued. CLINICAL TRIAL ID:
      NCT00673049.

PMID- 25395284
TI  - Effects of inspiratory muscle training in elderly women on respiratory muscle
      strength, diaphragm thickness and mobility.
AB  - BACKGROUND: Aging results in a decline in the function of the respiratory
      muscles. Inspiratory muscle training is emerging as a possible intervention to
      attenuate the decline of respiratory muscles in the elderly. The aim of this
      study was to evaluate the efficacy of inspiratory muscle training on respiratory
      strength, diaphragm thickness, and diaphragmatic mobility in elderly women.
      METHODS: This was a controlled, randomized, and double-blind clinical trial,
      performed on 22 elderly women distributed in two groups, training (TG) and
      control (CG). Over an 8-week period a moderate intensity inspiratory muscle
      training protocol was followed in the TG, while CG followed a sham protocol. In
      addition maximum expiratory and inspiratory pressure, mobility of the diaphragm
      and diaphragmatic thickness were evaluated by ultrasound. RESULTS: After
      training, in TG maximal inspiratory pressure, maximal expiratory pressure,
      diaphragm thickness, and mobility increased by 37%, 13%, 11%, and 9%
      respectively, and their values were significantly higher than CG (p < .005, p =
      .013, p = .001, and p = .001). CONCLUSION: Inspiratory muscle training of
      moderate intensity improves respiratory muscle strength, diaphragm thickness, and
      diaphragm mobility in elderly women and it should be considered to minimize
      changes associated with senescence.

PMID- 25395291
TI  - Soil pH determines microbial diversity and composition in the park grass
      experiment.
AB  - The Park Grass experiment (PGE) in the UK has been ongoing since 1856. Its
      purpose is to study the response of biological communities to the long-term
      treatments and associated changes in soil parameters, particularly soil pH. In
      this study, soil samples were collected across pH gradient (pH 3.6-7) and a range
      of fertilizers (nitrogen as ammonium sulfate, nitrogen as sodium nitrate,
      phosphorous) to evaluate the effects nutrients have on soil parameters and
      microbial community structure. Illumina 16S ribosomal RNA (rRNA) amplicon
      sequencing was used to determine the relative abundances and diversity of
      bacterial and archaeal taxa. Relationships between treatments, measured soil
      parameters, and microbial communities were evaluated. Clostridium, Bacteroides,
      Bradyrhizobium, Mycobacterium, Ruminococcus, Paenibacillus, and Rhodoplanes were
      the most abundant genera found at the PGE. The main soil parameter that
      determined microbial composition, diversity, and biomass in the PGE soil was pH.
      The most probable mechanism of the pH impact on microbial community may include
      mediation of nutrient availability in the soil. Addition of nitrogen to the PGE
      plots as ammonium sulfate decreases soil pH through increased nitrification,
      which causes buildup of soil carbon, and hence increases C/N ratio. Plant species
      richness and plant productivity did not reveal significant relationships with
      microbial diversity; however, plant species richness was positively correlated
      with soil microbial biomass. Plants responded to the nitrogen treatments with an
      increase in productivity and a decrease in the species richness. 

PMID- 25395292
TI  - Reagent and labor cost optimization through automation of fluorescence in situ
      hybridization (FISH) with the VP 2000: an Italian case study.
AB  - In the modern molecular diagnostic laboratory, cost considerations are of
      paramount importance. Automation of complex molecular assays not only allows a
      laboratory to accommodate higher test volumes and throughput but also has a
      considerable impact on the cost of testing from the perspective of reagent costs,
      as well as hands-on time for skilled laboratory personnel. The following study
      tracked the cost of labor (hands-on time) and reagents for fluorescence in situ
      hybridization (FISH) testing in a routine, high-volume pathology and cytogenetics
      laboratory in Treviso, Italy, over a 2-y period (2011-2013). The laboratory
      automated FISH testing with the VP 2000 Processor, a deparaffinization,
      pretreatment, and special staining instrument produced by Abbott Molecular, and
      compared hands-on time and reagent costs to manual FISH testing. The results
      indicated significant cost and time saving when automating FISH with VP 2000 when
      more than six FISH tests were run per week. At 12 FISH assays per week, an
      approximate total cost reduction of 55% was observed. When running 46 FISH
      specimens per week, the cost saving increased to 89% versus manual testing. The
      results demonstrate that the VP 2000 processor can significantly reduce the cost
      of FISH testing in diagnostic laboratories. 

PMID- 25395293
TI  - What do hemolyzed whole-blood specimens look like? Analysis with a CellaVision
      DM96 automated image analysis system.
AB  - We planned an original study to investigate the morphological changes caused by
      spurious hemolysis of whole-blood samples, analyzed using an automated image
      analysis system. Seven whole-blood specimens anticoagulated with EDTA were pooled
      and divided in two aliquots. The former was left untreated, whereas the latter
      was subjected to mechanical hemolysis by forced aspiration with an insulin
      syringe. The complete blood cell count was performed on a Sysmex XE-2100, and the
      aliquots were then processed with CellaVision DM96. In spuriously hemolyzed
      samples, the main findings included a rarefaction of erythrocytes, the presence
      of a remarkable number of cellular debris, a greater degree of microcytosis and
      anisocytosis, the appearance of band neutrophils, a shift of values between
      lymphocytes and monocytes, and an increase in smudge cells, artifacts, and large
      platelets. The results of this study demonstrate for the first time that blood
      cell morphology may be consistently biased in spuriously hemolyzed whole blood
      and that the use of an automated image analysis system such as the CellaVision
      DM96 may be a suitable approach to identify spurious hemolysis in whole-blood
      specimens. 

PMID- 25395294
TI  - Universes collide: combining immunotherapy with targeted therapy for cancer.
AB  - There have been significant advances in the past several years with regard to
      targeted therapy and immunotherapy for cancer. This is highlighted in melanoma,
      where treatment with targeted therapy (against the BRAF oncoprotein) results in
      responses in the majority of patients, although the duration of response is
      limited. In contrast, treatment with immunotherapy results in a lower response
      rate, but one that tends to be more durable. Insights about mechanisms of
      response and potential synergy between these treatment strategies for melanoma
      are a focus of this review, with opportunities to extend these insights to the
      treatment of other cancers. SIGNIFICANCE: Two major advances in melanoma have
      occurred concurrently and involve treatment with targeted therapy and immune
      checkpoint blockade. However, each of these approaches has limitations with
      regard to overall response rates or duration of response. To address this,
      investigators have proposed combining these strategies, and this concept is being
      tested empirically in clinical trials. There is a scientific rationale supporting
      the combination of targeted therapy and immunotherapy, and these concepts are
      discussed herein.

PMID- 25395295
TI  - Is sexual conflict an "engine of speciation"?
AB  - At the end of the last century, sexual conflict was identified as a powerful
      engine of speciation, potentially even more important than ecological selection.
      Earlier work that followed--experimental, comparative, and mathematical--provided
      strong initial support for this assertion. However, as the field matures, both
      the power of sexual conflict and constraints on the evolution of reproductive
      isolation as driven by sexual conflict are becoming better understood. From
      theoretical studies, we now know that speciation is only one of several possible
      evolutionary outcomes of sexual conflict. In line with these predictions, both
      experimental evolution studies and comparative analyses of fertilization proteins
      and of species richness show that sexual conflict leads to, or is associated
      with, reproductive isolation and speciation in some cases but not in others.
      Increased genetic variation (especially in females) without reproductive
      isolation is an underappreciated consequence of sexually antagonistic selection.

PMID- 25395298
TI  - Effects of standardized extract of Ginkgo biloba leaves EGb761 on mitochondrial
      functions: mechanism(s) of action and dependence on the source of mitochondria
      and respiratory substrate.
AB  - In this work, the effects of standardized dry extract of Ginkgo biloba leaves,
      EGb761, on the respiration of rat heart and liver mitochondria were investigated.
      We revealed uncoupling of oxidative phosphorylation in rat heart mitochondria by
      EGb761 which was not observed in liver mitochondria respiring on pyruvate +
      malate; oxidation of succinate in heart mitochondria was inhibited by EGb761,
      concentration-dependently, almost completely at 1.00 mg/mL. Uncoupling effect of
      EGb761 was found to be due to increase in H(+) and K(+) permeability of inner
      membrane of mitochondria which is most likely to be mediated by the ATP/ADP
      translocator and uncoupling proteins. EGb761 depressed State 3 respiration with
      pyruvate + malate (similarly in heart and liver mitochondria) and succinate
      (stronger than with pyruvate + malate) but not respiratory chain Complex IV;
      inhibition of respiration was not restored by uncoupler indicating the inhibitory
      action of EGb761 on the respiratory complexes preceding to Complex IV and/or on
      the substrate transport. Moreover, EGb761 rapidly reduced pure cytochrome c. This
      property of EGb761 together with the observed uncoupling of oxidative
      phosphorylation and reduction of H2O2 accumulation may be beneficial for the cell
      in the prevention of apoptosis and protection of cellular functions in
      pathological situations. 

PMID- 25395296
TI  - Glial cell development and function in zebrafish.
AB  - The zebrafish is a premier vertebrate model system that offers many experimental
      advantages for in vivo imaging and genetic studies. This review provides an
      overview of glial cell types in the central and peripheral nervous system of
      zebrafish. We highlight some recent work that exploited the strengths of the
      zebrafish system to increase the understanding of the role of Gpr126 in Schwann
      cell myelination and illuminate the mechanisms controlling oligodendrocyte
      development and myelination. We also summarize similarities and differences
      between zebrafish radial glia and mammalian astrocytes and consider the
      possibility that their distinct characteristics may represent extremes in a
      continuum of cell identity. Finally, we focus on the emergence of zebrafish as a
      model for elucidating the development and function of microglia. These recent
      studies have highlighted the power of the zebrafish system for analyzing
      important aspects of glial development and function. 

PMID- 25395299
TI  - PTCH1 mutation is a frequent event in oesophageal basaloid squamous cell
      carcinoma.
AB  - Basaloid squamous cell carcinoma (BSCC) is a rare and poorly differentiated
      variant of typical squamous cell carcinoma, and is characterised in part by
      activation of the Wnt signalling pathway. We previously demonstrated that
      constitutive activation of the Wnt signalling pathway by epigenetic silencing of
      secreted frizzled-related protein 4 (SFRP4) is observed in this tumour.
      Increasing evidence shows that the Wnt signalling pathway cross-talks with other
      developmental pathways, including the Hedgehog (HH) pathway. The HH pathway is
      stimulated by inactivating mutations of PTCH1, which have a well-described
      oncogenic role in basal cell carcinoma (BCC) of the skin. We employed polymerase
      chain reaction followed by direct sequencing to detect inactivating mutations of
      PTCH1 using archival tissue samples of 30 oesophageal BSCCs. The frequency of
      PTCH1 mutation was compared to that of Wnt component genes that we reported
      previously. We found PTCH1 mutations in 53.3% (16/30) of cases, revealing T1195S
      as a hotspot mutation. This frequency is quite high for cancers other than BCC of
      the skin, and PTCH1 mutations were almost mutually exclusive with mutations in
      APC, Axin1 and Axin2. Considering the fact that activation of Wnt signalling via
      down-regulation of APC and SFRP5 due to promoter methylation is observed in BCC
      of the skin, Wnt signalling activation in oesophageal BSCC might be a secondary
      effect of the PTCH1-inactivating mutations. These findings suggest that the HH
      and Wnt pathways coordinately contribute to tumourigenesis in oesophageal BSCC.
      Furthermore, this study provides a potential therapeutic application for HH
      pathway inhibitors in oesophageal BSCC with highly malignant potential. 

PMID- 25395297
TI  - Emerging principles governing signal transduction by pattern-recognition
      receptors.
AB  - The problem of recognizing and disposing of non-self-organisms, whether for
      nutrients or defense, predates the evolution of multicellularity. Accordingly,
      the function of the innate immune system is often intimately associated with
      fundamental aspects of cell biology. Here, we review our current understanding of
      the links between cell biology and pattern-recognition receptors of the innate
      immune system. We highlight the importance of receptor localization for the
      detection of microbes and for the initiation of antimicrobial signaling pathways.
      We discuss examples that illustrate how pattern-recognition receptors influence,
      and are influenced by, the general membrane trafficking machinery of mammalian
      cells. In the future, cell biological analysis likely will rival pure genetic
      analysis as a tool to uncover fundamental principles that govern host-microbe
      interactions. 

PMID- 25395300
TI  - Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and
      immune rejection in murine corneal allograft model.
AB  - Although corneal allotransplantation is performed in the immune-privileged
      cornea, many grafts are still rejected after transplantation. This study examined
      the role of chemokine receptor D6 expression in a corneal allograft rejection,
      investigated the modulation of D6 expression in cells, and determined the effect
      of D6 on graft survival. Interestingly, D6 was highly expressed in CD45 -: cells
      and the corneal epithelium of accepted corneal allografts. From the mouse corneal
      allograft model, TGF-beta was found to play a key role in D6 up-regulation,
      leading to reduced CCL2, CCL5, and CCL3. To modulate D6 chemokine binding, a D6MT
      was developed and showed effective chemokine trapping through SPR and FACS
      assays. By treating corneal allografts with D6MT, the allograft survival rate was
      improved, and (lymph) angiogenesis was reduced. Direct allosensitization and DC
      LN homing was drastically reduced in the mouse corneal allograft model. These
      findings suggest that TGF-beta is a positive regulator of D6 expression, and it
      is a potential therapeutic target to enhance the survival of corneal allografts. 

PMID- 25395301
TI  - Lymphocytic choriomeningitis virus persistence promotes effector-like memory
      differentiation and enhances mucosal T cell distribution.
AB  - Vaccines are desired that maintain abundant memory T cells at nonlymphoid sites
      of microbial exposure, where they may be anatomically positioned for immediate
      pathogen interception. Here, we test the impact of antigen persistence on mouse
      CD8 and CD4 T cell distribution and differentiation by comparing responses to
      infections with different strains of LCMV that cause either acute or chronic
      infections. We used in vivo labeling techniques that discriminate between T cells
      present within tissues and abundant populations that fail to be removed from
      vascular compartments, despite perfusion. LCMV persistence caused up to ~30-fold
      more virus-specific CD8 T cells to distribute to the lung compared with acute
      infection. Persistent infection also maintained mucosal-homing alpha4beta7
      integrin expression, higher granzyme B expression, alterations in the expression
      of the TRM markers CD69 and CD103, and greater accumulation of virus-specific CD8
      T cells in the large intestine, liver, kidney, and female reproductive tract.
      Persistent infection also increased LCMV-specific CD4 T cell quantity in mucosal
      tissues and induced maintenance of CXCR4, an HIV coreceptor. This study clarifies
      the relationship between viral persistence and CD4 and CD8 T cell distribution
      and mucosal phenotype, indicating that chronic LCMV infection magnifies T cell
      migration to nonlymphoid tissues. 

PMID- 25395302
TI  - gammadelta T cells promote inflammation and insulin resistance during high fat
      diet-induced obesity in mice.
AB  - gammadelta T cells are resident in AT and increase during diet-induced obesity.
      Their possible contribution to the inflammatory response that accompanies diet
      induced obesity was investigated in mice after a 5 to 10 week milk HFD. The HFD
      resulted in significant increases in CD44(hi), CD62L(lo), and TNF-alpha(+)
      gammadelta T cells in eAT of WT mice. Mice deficient in all gammadelta T cells
      (TCRdelta(-/-)) or only Vgamma4 and Vgamma6 subsets (Vgamma4/6(-/-)) were
      compared with WT mice with regard to proinflammatory cytokine production and
      macrophage accumulation in eAT. Obesity among these mouse strains did not differ,
      but obese TCRdelta(-/-) and Vgamma4/6(-/-) mice had significantly reduced eAT
      expression of F4/80, a macrophage marker, and inflammatory mediators CCL2 and IL
      6 compared with WT mice. Obese TCRdelta(-/-) mice had significantly reduced
      CD11c(+) and TNF-alpha(+) macrophage accumulation in eAT after 5 and 10 weeks on
      the HFD, and obese Vgamma4/6(-/-) mice had significantly increased CD206(+)
      macrophages in eAT after 5 weeks on the diet and significantly reduced
      macrophages after 10 weeks. Obese TCRdelta(-/-) mice had significant reductions
      in systemic insulin resistance and inflammation in liver and skeletal muscle
      after longer-term HFD feeding (10 and 24 weeks). In vitro studies revealed that
      isolated gammadelta T cells directly stimulated RAW264.7 macrophage TNF-alpha
      expression but did not stimulate inflammatory mediator expression in 3T3-L1
      adipocytes. These findings are consistent with a role for gammadelta T cells in
      the proinflammatory response that accompanies diet-induced obesity. 

PMID- 25395304
TI  - Study on the efficacy and safety of Jinlida in patients with inadequately
      controlled type-2 diabetes and dyslipidemia under life style intervention (ENJOY
      LIFE Study).

PMID- 25395303
TI  - Human neutrophil formyl peptide receptor phosphorylation and the mucosal
      inflammatory response.
AB  - Bacterial/mitochondrial fMLF analogs bind FPR1, driving accumulation/activation
      of PMN at sites of infection/injury, while promoting wound healing in epithelia.
      We quantified levels of UFPR1 and TFPR1 in isolated PMN by use of
      phosphosensitive NFPRb and phosphorylation-independent NFPRa antibodies. UFPR1
      and total TFPR were assessed inflamed mucosa, observed in human IBD. In isolated
      PMN after fMLF stimulation, UFPR1 declined 70% ((fMLF)EC50 = 11 +/- 1 nM; t1/2 =
      15 s) and was stable for up to 4 h, whereas TFPR1 changed only slightly.
      Antagonists (tBoc-FLFLF, CsH) and metabolic inhibitor NaF prevented the fMLF
      dependent UFPR1 decrease. Annexin A1 fragment Ac2-26 also induced decreases in
      UFPR1 ((Ac2-26)EC50 ~ 3 uM). Proinflammatory agents (TNF-alpha, LPS), phosphatase
      inhibitor (okadaic acid), and G-protein activator (MST) modestly increased
      (fMLF)EC50, 2- to 4-fold, whereas PTX, Ca(2+) chelators (EGTA/BAPTA), H2O2, GM
      CSF, ENA-78, IL-1RA, and LXA4 had no effect. Aggregation-inducing PAF, however,
      strongly inhibited fMLF-stimulated UFPR1 decreases. fMLF-driven PMN also
      demonstrated decreased UFPR1 after traversing monolayers of cultured intestinal
      epithelial cells, as did PMN in intestinal mucosal samples, demonstrating active
      inflammation from UC patients. Total TFPR remained high in PMN within inflamed
      crypts, migrating through crypt epithelium, and in the lamina propria-adjoining
      crypts, but UFPR1 was only observed at some peripheral sites on crypt aggregates.
      Loss of UFPR1 in PMN results from C-terminal S/T phosphorylation. Our results
      suggest G protein-insensitive, fMLF-dependent FPR1 phosphorylation in isolated
      suspension PMN, which may manifest in fMLF-driven transmigration and potentially,
      in actively inflamed tissues, except at minor discrete surface locations of PMN
      containing crypt aggregates. 

PMID- 25395305
TI  - Aligned genomic data compression via improved modeling.
AB  - With the release of the latest Next-Generation Sequencing (NGS) machine, the
      HiSeq X by Illumina, the cost of sequencing the whole genome of a human is
      expected to drop to a mere $1000. This milestone in sequencing history marks the
      era of affordable sequencing of individuals and opens the doors to personalized
      medicine. In accord, unprecedented volumes of genomic data will require storage
      for processing. There will be dire need not only of compressing aligned data, but
      also of generating compressed files that can be fed directly to downstream
      applications to facilitate the analysis of and inference on the data. Several
      approaches to this challenge have been proposed in the literature; however, focus
      thus far has been on the low coverage regime and most of the suggested
      compressors are not based on effective modeling of the data. We demonstrate the
      benefit of data modeling for compressing aligned reads. Specifically, we show
      that, by working with data models designed for the aligned data, we can improve
      considerably over the best compression ratio achieved by previously proposed
      algorithms. Our results indicate that the pareto-optimal barrier for compression
      rate and speed claimed by Bonfield and Mahoney (2013) [Bonfield JK and Mahoneys
      MV, Compression of FASTQ and SAM format sequencing data, PLOS ONE, 8(3):e59190,
      2013.] does not apply for high coverage aligned data. Furthermore, our improved
      compression ratio is achieved by splitting the data in a manner conducive to
      operations in the compressed domain by downstream applications. 

PMID- 25395306
TI  - Amyloidogenic and non-amyloidogenic transthyretin variants interact differently
      with human cardiomyocytes: insights into early events of non-fibrillar tissue
      damage.
AB  - TTR (transthyretin) amyloidoses are diseases characterized by the aggregation and
      extracellular deposition of the normally soluble plasma protein TTR. Ex vivo and
      tissue culture studies suggest that tissue damage precedes TTR fibril deposition,
      indicating that early events in the amyloidogenic cascade have an impact on
      disease development. We used a human cardiomyocyte tissue culture model system to
      define these events. We previously described that the amyloidogenic V122I TTR
      variant is cytotoxic to human cardiac cells, whereas the naturally occurring,
      stable and non-amyloidogenic T119M TTR variant is not. We show that most of the
      V122I TTR interacting with the cells is extracellular and this interaction is
      mediated by a membrane protein(s). In contrast, most of the non-amyloidogenic
      T119M TTR associated with the cells is intracellular where it undergoes lysosomal
      degradation. The TTR internalization process is highly dependent on membrane
      cholesterol content. Using a fluorescent labelled V122I TTR variant that has the
      same aggregation and cytotoxic potential as the native V122I TTR, we determined
      that its association with human cardiomyocytes is saturable with a KD near 650
      nM. Only amyloidogenic V122I TTR compete with fluorescent V122I for cell-binding
      sites. Finally, incubation of the human cardiomyocytes with V122I TTR but not
      with T119M TTR, generates superoxide species and activates caspase 3/7. In
      summary, our results show that the interaction of the amyloidogenic V122I TTR is
      distinct from that of a non-amyloidogenic TTR variant and is characterized by its
      retention at the cell membrane, where it initiates the cytotoxic cascade. 

PMID- 25395307
TI  - Anatomical variations and neurosurgical significance of Liliequist's membrane.
AB  - INTRODUCTION: Liliequist's membrane is an arachnoid membrane that forms a barrier
      within the basilar cisternal complex. This structure is an important landmark in
      approaches to the sellar and parasellar regions. The importance of this membrane
      was largely recognized after the advance of neuroendoscopic techniques. Many
      studies were, thereafter, published reporting different anatomic findings.
      METHOD: A detailed search for studies reporting anatomic and surgical findings of
      Liliequist's membrane was performed using "PubMed," and included all the
      available literature. Manual search for manuscripts was also conducted on
      references of papers reporting reviews. RESULTS: Liliequist's membrane has
      received more attention recently. The studies have reported widely variable
      results, which were systematically organized in this paper to address the
      controversy. CONCLUSION: Regardless of its clinical and surgical significance,
      the anatomy of Liliequist's membrane is still a matter of debate.

PMID- 25395308
TI  - Assessing the engagement, learning, and overall experience of students operating
      an atomic absorption spectrophotometer with remote access technology.
AB  - The use of internet-based technologies in the teaching of laboratories has
      emerged as a promising education tool. This study evaluated the effectiveness of
      using remote access technology to operate an atomic absorption spectrophotometer
      in analyzing the iron content in a crude myoglobin extract. Sixty-two students
      were surveyed on their level of engagement, learning, and overall experience.
      Feedback from students suggests that the use of remote access technology is
      effective in teaching students the principles of chemical analysis by atomic
      absorption spectroscopy.

PMID- 25395309
TI  - Electrophysiological dynamics reveal distinct processing of stimulus-stimulus and
      stimulus-response conflicts.
AB  - The present study examined electroencephalogram profiles on a novel stimulus
      response compatibility (SRC) task in order to elucidate the distinct brain
      mechanisms of stimulus-stimulus (S-S) and stimulus-response (S-R) conflict
      processing. The results showed that the SRC effects on reaction times (RTs) and
      N2 amplitudes were additive when both S-S and S-R conflicts existed. We also
      observed that, for both RTs and N2 amplitudes, the conflict adaptation effects
      the reduced SRC effect following an incongruent trial versus a congruent trial
      were present only when two consecutive trials involved the same type of conflict.
      Time-frequency analysis revealed that both S-S and S-R conflicts modulated power
      in the theta band, whereas S-S conflict additionally modulated power in the alpha
      and beta bands. In summary, our findings provide insight into the domain-specific
      conflict processing and the modular organization of cognitive control. 

PMID- 25395310
TI  - Salvia miltiorrhiza injection on pulmonary heart disease: a systematic review and
      meta-analysis.
AB  - Cor pulmonale (pulmonary heart disease) is a chronic progressive complicated
      disease for which treatment needs to be sustained all the time, creating a great
      financial burden on individuals and society. In order to improve the life quality
      of cor pulmonale patients and decrease the dosage and quantity of the routine
      treatment, in China, TCM is often administered to patients with cor pulmonale.
      The results of many clinical trials have indicated that Salvia miltiorrhiza and
      complex Salvia miltiorrhiza injection may be an alternative medicine for cor
      pulmonale. With the purpose to prove whether Salvia miltiorrhiza and complex
      Salvia miltiorrhiza benefit the cor pulmonale patients, respectively, we carried
      out a systematic review to evaluate the efficacy and safety of Salvia
      miltiorrhiza and complex Salvia miltiorrhiza injection in cor pulmonale patients.
      Overall, 2,715 patients were identified from 35 randomized controlled trials. The
      meta-analysis used I(2) test for heterogeneity and chose random or fixed model
      according to heterogeneity of included studies. Clinical outcomes were evaluated
      by total effectiveness rate, partial pressure of oxygen ( PaO 2) and carbon
      dioxide ( PaCO 2), hemorheology, mPAP and adverse effects. Compared with routine
      medicine treatment alone, routine medicine treatment plus Salvia miltiorrhiza or
      complex Salvia miltiorrhiza injection showed better outcomes: A significantly
      higher clinical effectiveness rate ratio (p < 0.001), increase in PaO 2 (p <
      0.001) and decrease in PaCO 2 (p < 0.001), improvement in hemorheology (p <
      0.001), and alleviation in mPAP (p < 0.05). There is no obvious adverse effect
      reported. In summary, there are some evidences suggesting that Salvia
      miltiorrhiza or complex Salvia miltiorrhiza injection are active in cor
      pulmonale, however, the results were limited by the methodological flaws of the
      included studies. Long-term and high quality clinical trials are needed to
      provide more conclusive evidence for the future use of Salvia miltiorrhiza
      injection. 

PMID- 25395311
TI  - Ibuprofen sodium is absorbed faster than standard Ibuprofen tablets: results of
      two open-label, randomized, crossover pharmacokinetic studies.
AB  - BACKGROUND: A novel ibuprofen (IBU) formulation, Advil((r)) Film-Coated Tablets
      (IBUNa), was developed. OBJECTIVE: Pharmacokinetic comparison of IBUNa versus
      other IBU formulations. STUDY DESIGN: Two randomized, single-dose, open-label,
      five-way crossover pharmacokinetic studies. SETTING: Inpatient research clinic.
      SUBJECTS: Seventy-one healthy adult volunteers. INTERVENTION: Study 1: In three
      periods, fasted subjects received 400-mg IBU dose equivalents as IBUNa 2 * 256
      mg, Advil((r)) Liqui-Gels((r)) (IBULG) 2 * 200 mg, and Motrin((r)) IB (IBUMot) 2
      * 200 mg tablets. In two periods following a high-fat breakfast, subjects
      received 400-mg IBU dose equivalents as IBUNa 2 * 256 mg and IBULG 2 * 200 mg.
      Study 2: In five study periods, fasted subjects received 400-mg IBU dose
      equivalents as IBUNa 2 * 256 mg, Advil((r)) FastGel((r)) (IBUFG) 2 * 200 mg,
      Nurofen((r)) (IBUNur) 2 * 200 mg, Advil((r)) (IBUAdv) 2 * 200 mg, and
      Nurofen((r)) Express containing IBU lysinate (IBULys) 2 * 342 mg. MAIN OUTCOME
      MEASURE: Log-transformed area under the plasma concentration versus time curve to
      last observable concentration (AUCL) and maximum plasma concentration (C max)
      were the primary pharmacokinetic parameters; time to maximum measured plasma
      concentration (T max) was analyzed post hoc. RESULTS: IBUNa was bioequivalent to
      IBULG (fasted and fed) and IBUFG and IBULys (fasted) for rate (C max) and extent
      (AUCL) of IBU absorption. After fasting, AUCL was bioequivalent for IBUNa and
      IBUMot, IBUAdv, and IBUNur, but C max occurred significantly earlier with IBUNa.
      After fasting, median IBUNa T max was comparable to that for IBULG, IBUFG, and
      IBULys, but was much shorter than that for IBUMot, IBUNur, and IBUAdv. Food
      slowed absorption of IBUNa and IBULG similarly. All treatments were tolerated
      similarly. CONCLUSION: IBUNa is absorbed faster but to a similar extent as
      standard IBU formulations.

PMID- 25395312
TI  - Partial mycoheterotrophy in Pyroleae: nitrogen and carbon stable isotope
      signatures during development from seedling to adult.
AB  - Mycoheterotrophic plants (MHP) are divided into non-photosynthesizing full MHP
      and green-leaved partial or initial MHP. We investigated (13)C and (15)N isotope
      enrichment in five putatively partial MHP species in the tribe Pyroleae
      (Ericaceae): Chimaphila umbellata, Moneses uniflora, Orthilia secunda, Pyrola
      chlorantha and Pyrola minor, sampled from forest sites on Oland, Sweden. For M.
      uniflora and P. chlorantha, we investigated isotope signatures of subterranean
      seedlings (which are mycoheterotrophic), to examine how the use of seedlings
      instead of full MHP species (Hypopitys monotropa) as reference species affects
      the assessment of partial mycoheterotrophy. Our main findings were as follows:
      (1) All investigated Pyroleae species were enriched in (15)N compared to
      autotrophic reference plants. (2) significant fungal-derived C among the Pyroleae
      species was found for O. secunda and P. chlorantha. For the remaining species of
      C. umbellata, M. uniflora and P. minor, isotope signatures suggested adult
      autotrophy. (3) C and N gains, calculated using seedlings as a full MHP
      reference, yielded qualitatively similar results as when using H. monotropa as a
      reference. However, the estimated differences in C and N gains became larger when
      using seedlings as an MHP reference. (4) A previously unknown interspecific
      variation in isotope signature occurs during early ontogeny, from seed production
      to developing seedlings. Our findings suggest that there is a variation among
      Pyroleae species concerning partial mycoheterotrophy in adults. Adult autotrophy
      may be most common in Pyroleae species, and these species may not be as dependent
      on fungal-derived nutrients as some green orchids.

PMID- 25395313
TI  - Parasites suppress immune-enhancing effect of methionine in nestling great tits.
AB  - After birth, an organism needs to invest both in somatic growth and in the
      development of efficient immune functions to counter the effects of pathogens,
      and hence an investment trade-off is predicted. To explore this trade-off, we
      simultaneously exposed nestling great tits (Parus major) to a common
      ectoparasite, while stimulating immune function. Using a 2 * 2 experimental
      design, we first infested half of the nests with hen fleas (Ceratophyllus
      gallinae) on day 3 post-hatch and later, on day 9-13 post-hatch, and then
      supplemented half of the nestlings within each nest with an immuno-enhancing
      amino acid (methionine). We then assessed the non-specific immune response by
      measuring both the inflammatory response to a lipopolysaccharide (LPS) and
      assessing the levels of acute phase proteins (APP). In parasite-infested
      nestlings, methionine had a negative effect on body mass close to fledging.
      Methionine had an immune-enhancing effect in the absence of ectoparasites only.
      The inflammatory response to LPS was significantly lower in nestlings infested
      with fleas and was also lower in nestlings supplemented with methionine. These
      patterns of immune responses suggest an immunosuppressive effect of ectoparasites
      that could neutralise the immune-enhancing effect of methionine. Our study thus
      suggests that the trade-off between investment in life history traits and immune
      function is only partly dependent on available resources, but shows that
      parasites may influence this trade-off in a more complex way, by also inhibiting
      important physiological functions.

PMID- 25395314
TI  - NEOCENT: a randomised feasibility and translational study comparing neoadjuvant
      endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast
      cancer.
AB  - Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with
      oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess
      feasibility of recruiting patients to a study comparing chemotherapy versus
      endocrine therapy in postmenopausal women with ER-rich primary BC, and response
      as well as translational endpoints were assessed. Patients requiring neoadjuvant
      therapy were randomised to chemotherapy: 6 * 3-weekly cycles FE100C or endocrine
      therapy: letrozole 2.5 mg, daily for 18-23 weeks. Primary endpoints were
      recruitment feasibility and tissue collection. Secondary endpoints included
      clinical, radiological and pathological response rates, quality of life and
      translational endpoints. 63/80 patients approached were eligible, of those 44
      (70, 95% CI 57-81) were randomised. 12 (54.5, 95% CI 32.2-75.6) chemotherapy
      patients showed radiological objective response compared with 13 (59.1, 95% CI
      36.4-79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in
      both groups at days 2-4 and at surgery [fold change: 0.24 (95% CI 0.12-0.51) and
      0.24; (95% CI 0.15-0.37), respectively]. Plasma total cfDNA levels rose from
      baseline to week 8 [fold change: chemotherapy 2.10 (95% CI 1.47-3.00), letrozole
      1.47(95% CI 0.98-2.20)], and were maintained at surgery in the chemotherapy group
      [chemotherapy 2.63; 95% CI 1.56-4.41), letrozole 0.95 (95% CI 0.71-1.26)]. An
      increase in plasma let-7a miRNA was seen at surgery for patients with objective
      radiological response to chemotherapy. Recruitment and tissue collection
      endpoints were met; however, a larger trial was deemed unfeasible due to slow
      accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki
      67 and circulating biomarkers in both groups with increases in cfDNA and let-7a
      miRNA persisting until surgery for chemotherapy patients.

PMID- 25395315
TI  - Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in
      Hispanics and non-Hispanic whites with breast cancer.
AB  - Ethnic differences in patient genetics and breast cancer (BC) biology contribute
      to ethnic disparities in cancer presentation and patient outcome. We
      prospectively evaluated SNPs within phase I and phase II tamoxifen (TAM)
      metabolizing enzymes, and the estrogen receptor gene (ESR1), aiming to identify
      potential pharmacogenomic ethnicity patterns in an ER-positive BC cohort
      constituted of Hispanic and Non-Hispanic White (NHW) women in South Texas. Plasma
      concentrations of TAM/metabolites were measured using HPLC. CYP2C9, CYP2D6 and
      SULT1A1 genotypes were determined by DNA sequencing/Pyrosequencing technology.
      ESR1 PvuII and XbaI SNPs were genotyped using Applied Biosystems Taqman Allelic
      Discrimination Assay. Hispanics had higher levels of TAM, 4-hydroxytamoxifen, and
      endoxifen than NHWs. There was a higher prevalence of CYP2D6 EM within Hispanics
      than NHWs, which corresponded to higher endoxifen levels, but no differences were
      verified with regard to CYP2C9 and SULT1A1. We found a higher incidence of the
      wild type forms of the ESR1 in Hispanics than NHWs. The performance status, the
      disease stage at diagnosis, and the use of aromatase inhibitors might have
      overcome the overall favorable pharmacogenomics profile of Hispanics when
      compared to NHWs in relation to TAM therapy responsiveness. Our data strongly
      point to ethnical peculiarities related to pharmacogenomics and demographic
      features of TAM treated Hispanics and NHWs. In the era of pharmacogenomics and
      its ultimate goal of individualized, efficacious and safe therapy, cancer studies
      focused on the Hispanic population are warranted because this is the fastest
      growing major demographic group, and an understudied segment in the U.S.

PMID- 25395317
TI  - Metabolic isoenzyme shifts in cancer as potential novel therapeutic targets.
AB  - The functional redundancy of metabolic enzyme expression may present a new
      strategy for developing targeted therapies in cancer. To satisfy the increased
      metabolic demand required during neoplastic transformations and proliferation,
      cancer cells may rely on additional isoforms of a metabolic enzyme to satisfy the
      increased demand for metabolic precursors, which could subsequently render cancer
      cells more vulnerable to isoform-specific inhibitors. In this review, we provide
      a survey of common isoenzyme shifts that have been reported to be important in
      cancer metabolism and link those to metabolic pathways that currently have drugs
      in various stages of development. This phenomenon suggests a potentially new
      therapeutic strategy for the treatment of cancer by identifying shifts in the
      expression of metabolic isoenzymes between cancer and normal cells. We also
      delineate other putative metabolic isoenzymes that could be targets for novel
      targeted therapies for cancer. Changes in isoenzyme expression that occur during
      neoplastic transformations or in response to environmental pressure in cancer
      cells may result in isoenzyme diversity that may subsequently render cancer cells
      more vulnerable to isoform-specific inhibitors due to reliance on a single
      isoform to perform a vital enzymatic function. 

PMID- 25395316
TI  - Pathological non-response to chemotherapy in a neoadjuvant setting of breast
      cancer: an inter-institutional study.
AB  - To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could
      be used in the adjuvant setting. Sixteen pathologists of the European Working
      Group for Breast Screening Pathology reviewed the core biopsies of breast cancers
      treated with NAC and recorded the clinico-pathological findings (histological
      type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic
      count; tumor-infiltrating lymphocytes; necrosis) and data regarding the
      pathological response in corresponding surgical resection specimens. Analyses
      were carried out in a cohort of 490 cases by comparing the groups of patients
      showing pathological complete response (pCR) and partial response (pPR) with the
      group of non-responders (pathological non-response: pNR). Among other parameters,
      the lobular histotype and the absence of inflammation were significantly more
      common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2
      mm(2) and 18% of Ki67-positive cells best discriminated the pNR and pCR + pPR
      categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only
      the cut-off value of 9 mitosis discriminated the different response categories (p
      = 0.036) in the entire cohort. In the Luminal B/HER2- subgroup, a mitotic count
      <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular
      histotype and the absence of inflammation were independent predictors of pNR (p =
      0.024 and <0.001, respectively). Classical morphological parameters, such as
      lobular histotype and inflammation, confirmed their predictive value in response
      to NAC, particularly in the Luminal B/HER2- subgroup, which is a challenging
      breast cancer subtype from a therapeutic point of view. Mitotic count could
      represent an additional marker but has a poor positive predictive value.

PMID- 25395318
TI  - Novel and recurrent BRCA2 mutations in Italian breast/ovarian cancer families
      widen the ovarian cancer cluster region boundaries to exons 13 and 14.
AB  - Hereditary breast and ovarian cancer are mainly linked to mutations in BRCA1 and
      BRCA2 genes which confer a similar cumulative risk of developing breast cancer.
      Importantly, while BRCA2 mutation carriers generally have a lower cumulative risk
      for ovarian cancer, mutations clustered in the central portion of BRCA2 are
      associated with a higher proportion of ovarian compared with breast cancer cases.
      The boundaries of this ovarian cancer cluster region (OCCR) have been tentatively
      defined within a 3.3 kb region of BRCA2 exon 11, and herein, we reassessed these
      boundaries using our series of Italian breast/ovarian cancer families. We used
      direct sequencing to investigate BRCA mutations in 367 breast/ovarian cancer
      families. We also studied the association between the location of the mutations
      and the ovarian cancer phenotype in our cohort of BRCA2-mutated families. We
      observed the novel c.7309_7309delA frameshift mutation and the c.7007G>A
      deleterious mutation in BRCA2 exons 14 and 13, respectively, in five independent
      Italian families characterized by a high proportion of ovarian cancer cases. Of
      note, a significantly higher proportion of ovarian versus breast cancer cases was
      associated not only with mutations in the previously defined OCCR (OR = 5.91; p =
      0.004), but also with the exon 13-14 region (OR = 7.37; p = 0.001) in our BRCA2
      mutated families. Our data provide initial evidence for a novel putative OCCR in
      BRCA2 exons 13-14. 

PMID- 25395319
TI  - Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer:
      its correlation with pathological complete response to neoadjuvant chemotherapy.
AB  - The anti-tumor immune response was recently reported to play a critical role in
      the chemotherapeutic sensitivity of breast cancer. Therefore, we investigated the
      correlation between CD8+ and FOXP3+ tumor-infiltrating lymphocytes and the
      pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) in
      triple-negative breast cancer (TNBC), in conjunction with neoangiogenesis, basal
      and proliferation markers. CD8+ and FOXP3+ lymphocytes were assessed in biopsy
      specimens by double-staining immunohistochemistry, in combination with
      immunostaining of vasohibin-1, CD31, EGFR, CK5/6, and Ki-67. Earlier age, pre
      menopausal status, smaller tumor size, and high Ki-67 were significantly
      associated with pCR, as in high CD8+, high CD8+/FOXP3+ ratio, and low vasohibin-1
      positive ratio. Multivariate analysis did reveal that a high CD8+/FOXP3+ ratio
      was a strong predictor of pCR with an odds ratio of 5.32 (P = 0.005). High Ki-67
      was also significantly associated with pCR (P = 0.002). TNBCs with a high
      CD8+/FOXP3+ ratio and high Ki-67 had the highest pCR rate (70%) following NAC.
      However, the pCR rate of the patients with low CD8+/FOXP3+ ratio and low Ki-67
      was only 5%. The pCR rates of a high CD8+/FOXP3+ ratio and low Ki-67 patients and
      those with a low CD8+/FOXP3+ ratio and high Ki-67 were 24 and 21%, respectively.
      TNBCs with a high CD8+/FOXP3+ ratio were more sensitive to anthracycline and
      taxane-based chemotherapeutic regimens, and the CD8+/FOXP3+ ratio in conjunction
      with Ki-67 could predict pCR following NAC in TNBC. This predictor may represent
      a new surrogate for testing the efficacy of investigational agents in the
      neoadjuvant setting.

PMID- 25395320
TI  - Natural history of tumor growth and immune modulation in common spontaneous
      murine mammary tumor models.
AB  - Recent studies in patients with breast cancer suggest the immune microenvironment
      influences response to therapy. We aimed to evaluate the relationship between
      growth rates of tumors in common spontaneous mammary tumor models and immune
      biomarkers evaluated in the tumor and blood. TgMMTV-neu and C3(1)-Tag transgenic
      mice were followed longitudinally from birth, and MPA-DMBA-treated mice from the
      time of carcinogen administration, for the development of mammary tumors. Tumor
      infiltrating CD4(+) and CD8(+) T-cells, FOXP3(+) T-regulatory cells, and myeloid
      derived suppressor cells were assessed by flow cytometry. Serum cytokines were
      evaluated in subsets of mice. Fine needle aspirates of tumors were collected and
      RNA was isolated to determine levels of immune and proliferation markers. Age of
      tumor onset and kinetics of tumor growth were significantly different among the
      models. Mammary tumors from TgMMTV-neu contained a lower CD8/CD4 ratio than that
      of other models (p < 0.05). MPA-DMBA-induced tumors contained a higher percentage
      of FOXP3(+) CD4(+) T-cells (p < 0.01) and MDSC (p < 0.001) compared with the
      other models. Individuals with significantly slower tumor growth demonstrated
      higher levels of Type I serum cytokines prior to the development of lesions
      compared to those with rapid tumor growth. Moreover, the tumors of animals with
      more rapid tumor growth demonstrated a significant increase in the expression of
      genes associated with Type II immunity than those with slower-progressing tumors.
      These data provide a foundation for the development of in vivo models to explore
      the relationship between endogenous immunity and response to standard therapies
      for breast cancer.

PMID- 25395321
TI  - pREPORT: a multi-readout transcription reporter vector for fission yeast.
AB  - Transcription factors are prominent regulators of gene expression that execute
      responses to various intracellular and extracellular stimuli. Recombinant
      transcription reporter systems can be conveniently used to study the DNA binding
      preferences and regulatory activity of a transcription factor under a range of
      conditions. Several reporter genes have been used to study transcription
      regulation in the fission yeast Schizosaccharomyces pombe. Each of these
      reporters has distinct advantages, such as high sensitivity or ease of use, and
      limitations, such as prohibitive costs or use of hazardous substances. To combine
      the strengths and mitigate the weaknesses of individual reporter genes, we have
      created pREPORT, a flexible multi-readout transcription reporter vector for
      fission yeast that employs an enhanced GFP-lacZ fusion and a customizable minimal
      promoter. With pREPORT, gene expression driven by the transcription factor of
      interest can be quantified in a number of ways, both in live cells and in vitro,
      using a single reporter construct.

PMID- 25395322
TI  - Modeling relationships between catchment attributes and river water quality in
      southern catchments of the Caspian Sea.
AB  - Increasing land utilization through diverse forms of human activities, such as
      agriculture, forestry, urban growth, and industrial development, has led to
      negative impacts on the water quality of rivers. To find out how catchment
      attributes, such as land use, hydrologic soil groups, and lithology, can affect
      water quality variables (Ca(2+), Mg(2+), Na(+), Cl(-), HCO 3 (-) , pH, TDS, EC,
      SAR), a spatio-statistical approach was applied to 23 catchments in southern
      basins of the Caspian Sea. All input data layers (digital maps of land use, soil,
      and lithology) were prepared using geographic information system (GIS) and
      spatial analysis. Relationships between water quality variables and catchment
      attributes were then examined by Spearman rank correlation tests and multiple
      linear regression. Stepwise approach-based multiple linear regressions were
      developed to examine the relationship between catchment attributes and water
      quality variables. The areas (%) of marl, tuff, or diorite, as well as those of
      good-quality rangeland and bare land had negative effects on all water quality
      variables, while those of basalt, forest land cover were found to contribute to
      improved river water quality. Moreover, lithological variables showed the
      greatest most potential for predicting the mean concentration values of water
      quality variables, and noting that measure of EC and TDS have inversely
      associated with area (%) of urban land use. 

PMID- 25395323
TI  - Experimental determinations of soil copper toxicity to lettuce (Lactuca sativa)
      growth in highly different copper spiked and aged soils.
AB  - Accurate knowledge about factors and conditions determining copper (Cu) toxicity
      in soil is needed for predicting plant growth in various Cu-contaminated soils.
      Therefore, effects of Cu on growth (biomass production) of lettuce (Lactuca
      sativa) were tested on seven selected, very different soils spiked with Cu and
      aged for 2 months at 35  degrees C. Cu toxicity was expressed as pEC50(Cu(2+)),
      i.e., the negative logarithm of the EC50(Cu(2+)) activity to plant growth. The
      determined pEC50(Cu(2+)) was significantly and positively correlated with both
      the analytically readily available soil pH and concentration of dissolved organic
      carbon [DOC] which together could explain 87% of the pEC50(Cu(2+)) variation
      according to the simple equation: pEC50(Cu(2+)) = 0.98 * pH + 345 * [DOC] - 0.27.
      Other soil characteristics, including the base cation concentrations (Na(+),
      K(+), Ca(2+), Mg(2+)), the cation exchange capacity at soil pH (ECEC), and at pH
      7 (CEC7), soil organic carbon, clay content, and electric conductivity as well as
      the distribution coefficient (Kd) calculated as the ratio between total soil Cu
      and water-extractable Cu did not correlate significantly with pEC50(Cu(2+)).
      Consequently, Cu toxicity, expressed as the negative log of the Cu(2+) activity,
      to plant growth increases at increasing pH and DOC, which needs to be considered
      in future management of plant growth on Cu-contaminated soils. The developed
      regression equation allows identification of soil types in which the
      phytotoxicity potential of Cu is highest.

PMID- 25395324
TI  - Monomorphic ants undergo within-colony morphological changes along the metal
      pollution gradient.
AB  - In ants, intra and inter-colony variation in body size can be considerable, even
      in monomorphic species. It has been previously shown that size-related parameters
      can be environmentally sensitive. The shape of the body size distribution curve
      is, however, rarely investigated. In this study, we measured head widthes of the
      black garden ant Lasius niger workers using digital methods. The ants were
      sampled from 51 colonies originating from 19 sites located along a metal
      pollution gradient, established in a former mining area in Poland. Total zinc
      concentrations in random samples of small invertebrates were used as a measure of
      site pollution levels. We found that the skewness of head size distribution grows
      significantly in line with the pollution level of the site, ranging from values
      slightly below zero (about -0.5) in the least polluted site up to a positive
      value (about 1.5) in the most polluted site. This result indicates that the
      frequency of small ants grows as pollution levels increase. The coefficient of
      variation, as well as the measures of central tendency, was not related to the
      pollution level. Four hypotheses explaining the obtained results are proposed.
      The bias towards the higher frequency of small workers may result from energy
      limitation and/or metal toxicity, but may also have an adaptive function.

PMID- 25395326
TI  - Effect of biochar amendment on yield and photosynthesis of peanut on two types of
      soils.
AB  - Biochar has significant potential to improve crop performance. This study
      examined the effect of biochar application on the photosynthesis and yield of
      peanut crop grown on two soil types. The commercial peanut cultivar Middleton was
      grown on red ferrosol and redoxi-hydrosol (Queensland, Australia) amended with a
      peanut shell biochar gradient (0, 0.375, 0.750, 1.50, 3.00 and 6.00%, w/w,
      equivalent up to 85 t ha(-1)) in a glasshouse pot experiment. Biomass and pod
      yield, photosynthesis-[CO2] response parameters, leaf characteristics and soil
      properties (carbon, nitrogen (N) and nutrients) were quantified. Biochar
      significantly improved peanut biomass and pod yield up to 2- and 3-folds
      respectively in red ferrosol and redoxi-hydrosol. A modest (but significant)
      biochar-induced improvement of the maximum electron transport rate and saturating
      photosynthetic rate was observed for red ferrosol. This response was correlated
      to increased leaf N and accompanied with improved soil available N and biological
      N fixation. Biochar application also improved the availability of other soil
      nutrients, which appeared critical in improving peanut performance, especially on
      infertile redoxi-hydrosol. Our study suggests that application of peanut shell
      derived biochar has strong potential to improve peanut yield on red ferrosol and
      redoxi-hydrosol. Biochar soil amendment can affect leaf N status and
      photosynthesis, but the effect varied with soil type.

PMID- 25395325
TI  - The fish embryo test (FET): origin, applications, and future.
AB  - Originally designed as an alternative for the acute fish toxicity test according
      to, e.g., OECD TG 203, the fish embryo test (FET) with the zebrafish (Danio
      rerio) has been optimized, standardized, and validated during an OECD validation
      study and adopted as OECD TG 236 as a test to assess toxicity of embryonic forms
      of fish. Given its excellent correlation with the acute fish toxicity test and
      the fact that non-feeding developmental stages of fish are not categorized as
      protected stages according to the new European Directive 2010/63/EU on the
      protection of animals used for scientific purposes, the FET is ready for use not
      only for range-finding but also as a true alternative for the acute fish toxicity
      test, as required for a multitude of national and international regulations. If
      for ethical reasons-not accepted as a full alternative, the FET represents at
      least a refinement in the sense of the 3Rs principle. Objections to the use of
      the FET have mainly been based on the putative lack of biotransformation capacity
      and the assumption that highly lipophilic and/or high molecular weight substances
      might not have access to the embryo due to the protective role of the chorion.
      With respect to bioactivation, the only substance identified so far as not being
      activated in the zebrafish embryo is allyl alcohol; all other biotransformation
      processes that have been studied in more detail so far were found to be present,
      albeit, in some cases, at lower levels than in adult fish. With respect to larger
      molecules, the extension of the test duration to 96 h (i.e., beyond hatch) has-at
      least for the substances tested so far-compensated for the reduced access to the
      embryo; however, more research is necessary to fully explore the applicability of
      the FET to substances with a molecular weight >3 kDa as well as substances with a
      neurotoxic mode of action. An extension of the endpoints to also cover sublethal
      endpoints makes the FET a powerful tool for the detection of teratogenicity,
      dioxin-like activity, genotoxicity and mutagenicity, neurotoxicity, as well as
      various forms of endocrine disruption. 

PMID- 25395327
TI  - Human health risk assessment of pesticide residues in market-sold vegetables and
      fish in a northern metropolis of China.
AB  - With growing concerns about food safety and stricter national standards in China,
      attention has focused on vegetables and fish as they are an important part of the
      Chinese daily diet, and pesticide residues can accumulate in these foodstuffs.
      The local consumption habits of vegetables and fish were determined using
      questionnaires distributed in the major regions of the northern metropolis. Then,
      the samples of fruit-like vegetables, leafy and root vegetables, and five species
      of fish (freshwater and marine) were collected from supermarkets and traditional
      farmers' markets in the city. The concentrations and profiles of pesticide
      residues (hexachlorocyclohexane (HCH), dichlorodiphenyl trichloroethane (DDT),
      and endosulfan) in the samples were determined and compared. For the vegetables,
      the concentration ranges of SigmaDDT, SigmaHCH, and Sigmaendosulfan were not
      detectable (ND) to 10.4 ng/g fresh weight (f.w.), ND to 58.8 ng/g f.w., and ND to
      63.9 ng/g f.w., respectively. For the fish samples, the corresponding values were
      0.77-25.0 ng/g f.w., 0.02-1.42 ng/g f.w., and 1.22-22.1 ng/g f.w., respectively.
      Only one celery sample exceeded the maximum residue limits (MRLs) of HCH residues
      set by Chinese regulations (GB2763-2014). The estimated daily intakes (EDIs) and
      hazard ratios (HRs) were calculated using data from the recently published
      Exposure Factors Handbook for the Chinese Population. The EDIs and HRs showed
      that the levels of organochlorine pesticide (OCP) residues in vegetables and fish
      in this area are safe.

PMID- 25395328
TI  - Use of antidepressants and association with elective termination of pregnancy:
      population based case-control study.
AB  - OBJECTIVE: To assess whether the use of selective serotonin reuptake inhibitors
      (SSRIs), tricyclic antidepressants, mirtazapine, venlafaxine or other
      antidepressants is associated with late elective termination of pregnancy.
      DESIGN: Case-control study using data from national registers. SETTING: Denmark,
      Finland, and Norway during the period 1996-2007. POPULATION: A total of 14,902
      women were included as cases and 148,929 women were included as controls.
      METHODS: Cases were women with elective termination of pregnancy at 12-23 weeks
      of gestation. Controls continued their pregnancy and were matched with cases on
      key factors. MAIN OUTCOME MEASURES: Association between antidepressant use during
      pregnancy and elective termination of pregnancy at 12-23 weeks of gestation for
      fetal anomalies, or for maternal ill health or socio-economic disadvantage.
      RESULTS: At least one prescription of antidepressants was filled by 3.7% of the
      cases and 2.2% of the controls. Use of any type of antidepressant was associated
      with elective termination of pregnancy for maternal ill health or socio-economic
      disadvantage (odds ratio, OR 2.3; 95% confidence interval, 95% CI 2.0-2.5).
      Elective termination of pregnancy for fetal anomalies was associated with the use
      of mirtazapine (OR 2.2, 95% CI 1.1-4.5). There was no association between the use
      of any of the other antidepressants and elective termination of pregnancy for
      fetal anomalies. CONCLUSION: The use of any type of antidepressants was
      associated with elective termination of pregnancy at 12-23 weeks for maternal ill
      health or socio-economic disadvantage, but not with terminations for fetal
      anomalies. Further studies need to confirm the findings concerning mirtazapine
      and termination of pregnancy for fetal anomalies.

PMID- 25395329
TI  - Copper-zinc cross-modulation in prion protein binding.
AB  - In this paper we report a systematic XAS study of a set of samples in which
      Cu(II) was progressively added to complexes in which Zn(II) was bound to the
      tetra-octarepeat portion of the prion protein. This work extends previous EPR and
      XAS analysis in which, in contrast, the effect of adding Zn(II) to Cu(II)-tetra
      octarepeat complexes was investigated. Detailed structural analysis of the XAS
      spectra taken at both the Cu and Zn K-edge when the two metals are present at
      different relative concentrations revealed that Zn(II) and Cu(II) ions compete
      for binding to the tetra-octarepeat peptide by cross-regulating their relative
      binding modes. We show that the specific metal-peptide coordination mode depends
      not only, as expected, on the relative metal concentrations, but also on whether
      Zn(II) or Cu(II) was first bound to the peptide. In particular, it seems that the
      Zn(II) binding mode in the absence of Cu(II) is able to promote the formation of
      small peptide clusters in which triplets of tetra-octarepeats are bridged by
      pairs of Zn ions. When Cu(II) is added, it starts competing with Zn(II) for
      binding, disrupting the existing peptide cluster arrangement, despite the fact
      that Cu(II) is unable to completely displace Zn(II). These results may have a
      bearing on our understanding of peptide-aggregation processes and, with the
      delicate cross-regulation balancing we have revealed, seem to suggest the
      existence of an interesting, finely tuned interplay among metal ions affecting
      protein binding, capable of providing a mechanism for regulation of metal
      concentration in cells. 

PMID- 25395330
TI  - Spectroscopic and thermodynamic properties of recombinant heat shock protein A6
      from Camelus dromedarius.
AB  - Heat shock protein A6, also known as HSP70B', is a member of the Hsp70 family of
      molecular chaperones. Under stressed conditions, the level of HSPA6 increases
      substantially, and the protein has been targeted as a biomarker of cellular
      stress in several studies. We report the spectroscopic and thermodynamic
      properties of Arabian camel species cHSPA6, determined by measurement of
      intrinsic and extrinsic fluorescence emission, and use of far-UV circular
      dichroism and dynamic multimode spectroscopy. Our results showed that cHSPA6 has
      similar binding affinity for both ATP and ADP (K D = ~50 nM). Binding of ATP and
      ADP reduced the surface hydrophobicity of the protein, and slightly altered its
      secondary structure, suggesting localized conformational rearrangement after ATP
      or ADP binding. Dynamic multimode spectroscopy revealed that cHSPA6 unfolds
      through three transitions with melting points (T m) of 42.3 +/- 0.2, 61.3 +/-
      0.1, and 81.2 +/- 0.2  degrees C. To the best of the author's knowledge, and
      literature search, this is the first report of the spectroscopic and
      thermodynamic properties of the Arabian camel heat shock protein. 

PMID- 25395331
TI  - Stimulation of suicidal erythrocyte death by ellipticine.
AB  - Ellipticine is a potent antineoplastic alkaloid effective in part by triggering
      apoptosis. Mechanisms involved in ellipticine-induced apoptosis include
      mitochondrial depolarization and DNA damage. Erythrocytes lack mitochondria and
      nuclei but may nevertheless enter suicidal death or eryptosis, which is
      characterized by cell shrinkage and phosphatidylserine translocation to the
      erythrocyte surface. Stimulators of eryptosis include increase in cytosolic
      Ca(2+) activity ([Ca(2+)]i), ceramide formation and oxidative stress. This study
      tested whether ellipticine stimulates eryptosis. Phosphatidylserine exposure at
      the cell surface was estimated from annexin V binding, cell volume from forward
      scatter (FSC), [Ca(2+)]i from Fluo-3 fluorescence, ceramide abundance from
      binding of specific antibodies and reactive oxygen species from 2',7'
      dichlorodihydrofluorescein diacetate fluorescence. A 24-hr exposure of human
      erythrocytes to ellipticine (5 MUg/ml) significantly increased the percentage of
      annexin V binding cells, ceramide abundance and oxidative stress. Ellipticine did
      not significantly modify [Ca(2+)]i , and the stimulation of annexin V binding by
      ellipticine (5 MUg/ml) did not require the presence of extracellular Ca(2+).
      Ellipticine (5 MUg/ml) did not significantly modify FSC. Ionomycin (1 MUM, 1 hr)
      decreased FSC, an effect slightly but significantly blunted by ellipticine (5
      MUg/ml). Ellipticine thus stimulates phosphatidylserine translocation in the
      erythrocyte cell membrane, an effect at least partially due to stimulation of
      oxidative stress and ceramide formation.

PMID- 25395332
TI  - The influence of staff training on challenging behaviour in individuals with
      intellectual disability: a review.
AB  - Many individuals with intellectual disability engage in challenging behaviour.
      This can significantly limit quality of life and also negatively impact
      caregivers (e.g., direct care staff, family caregivers and teachers).
      Fortunately, efficacious staff training may alleviate some negative side effects
      of client challenging behaviour. Currently, a systematic review of studies
      evaluating whether staff training influences client challenging behaviour has not
      been conducted. The purpose of this article was to identify emerging patterns,
      knowledge gaps and make recommendations for future research on this topic. The
      literature search resulted in a total of 19 studies that met our inclusion
      criteria. Articles were separated into four staff training categories. Studies
      varied across sample size, support staff involved in training, study design,
      training duration and data collection strategy. A small sample size (n = 19) and
      few replication studies, alongside several other procedural limitations
      prohibited the identification of a best practice training approach. 

PMID- 25395333
TI  - Factors influencing severity of peri-implantitis.
AB  - OBJECTIVES: To retrospectively assess the influence of potential risk factors,
      primarily smoking and a prior history of periodontitis, on the severity of peri
      implantitis in patients referred for treatment of peri-implantitis. MATERIALS AND
      METHODS: Among 98 patients referred for treatment of peri-implantitis, 34
      patients fulfilled the inclusion criteria: one or several implants with peri
      implant marginal bone loss >=2 mm concomitant with bleeding and/or pus on
      probing. Information about health status, smoking habits, reason for tooth loss,
      and performed implant treatment were obtained from the patient charts and
      interviews. Moreover, a detailed extra- and intraoral examination was performed,
      including intraoral radiographs of all implants. Risk factors were evaluated by a
      two-way anova at patient level. RESULTS: Smoking and a prior history of
      periodontitis were significant risk factors for increased severity of peri
      implantitis. Furthermore, the presence of both smoking and a prior history of
      periodontitis did not further increase the severity of peri-implantitis, as
      compared to either of these two factors alone. Poor marginal fit of the
      suprastructure and extensive gingival imitations on implant-supported fixed full
      prostheses may also be potential risk factors. CONCLUSIONS: The study indicated
      that smoking and a prior history of periodontitis were important risk factors for
      increased severity of peri-implantitis, while concomitant presence of these two
      risk factors did not further increase the severity of peri-implantitis, as
      compared to either of these two risk factors alone. Therefore, early diagnosis
      and adequate treatment of peri-implantitis are important in patients with a prior
      history of periodontitis and in smokers to minimize the risk of advanced peri
      implantitis in conjunction with focus on known risk factors, including meticulous
      infection control before implant treatment and a systematic maintenance care
      program.

PMID- 25395334
TI  - Nutrition and malnutrition in low- and middle-income countries.

PMID- 25395335
TI  - Tackling undernutrition in children--new opportunities for innovation and action.

PMID- 25395336
TI  - Antifungal prophylaxis in liver transplantation: a systematic review and network
      meta-analysis.
AB  - Invasive fungal infections (IFIs) cause significant morbidity and mortality in
      liver transplant recipients, but the need and best agent for prophylaxis is
      uncertain. A comprehensive literature search was performed to identify randomized
      controlled trials comparing regimens for antifungal prophylaxis in liver
      transplant recipients. Direct comparisons were made between treatments using
      random-effects meta-analysis and a Bayesian network meta-analysis was performed
      for the primary end point of proven IFI. Fourteen studies met inclusion criteria,
      reporting comparisons of fluconazole, liposomal amphotericin B (L-AmB),
      itraconazole, micafungin and placebo. Overall, antifungal prophylaxis reduced the
      rate of proven IFI (odds ratio [OR] 0.37, confidence interval [CI] 0.19-0.72, p =
      0.003), suspected or proven IFI (OR 0.40, CI 0.25-0.66, p = 0.0003) and mortality
      due to IFI (OR 0.32, CI 0.10-0.83, p = 0.02) when compared to placebo. All-cause
      mortality was not significantly affected. There was no difference in risk of
      adverse events requiring cessation of prophylaxis (OR 1.11, 95% CI 0.48-2.55, p =
      0.81). In the network meta-analysis an equivalent reduction in the rate of IFI
      was seen with fluconazole (OR 0.21, CI 0.06-0.57) and L-AmB (OR 0.21, CI 0.05
      0.71) compared with placebo. Routine prophylaxis with fluconazole or L-AmB
      reduces the incidence of IFI following liver transplantation, and the available
      evidence suggests that the two are equivalent in efficacy. 

PMID- 25395337
TI  - Atomic-resolution three-dimensional structure of amyloid beta fibrils bearing the
      Osaka mutation.
AB  - Despite its central importance for understanding the molecular basis of
      Alzheimer's disease (AD), high-resolution structural information on amyloid beta
      peptide (Abeta) fibrils, which are intimately linked with AD, is scarce. We
      report an atomic-resolution fibril structure of the Abeta1-40 peptide with the
      Osaka mutation (E22Delta), associated with early-onset AD. The structure, which
      differs substantially from all previously proposed models, is based on a large
      number of unambiguous intra- and intermolecular solid-state NMR distance
      restraints. 

PMID- 25395338
TI  - Evolution of multiple sclerosis in France since the beginning of hepatitis B
      vaccination.
AB  - Since the implementation of the mass vaccination campaign against hepatitis B in
      France, the appearance of multiple sclerosis, sometimes occurring in the
      aftermath of vaccinations, led to the publication of epidemiological
      international studies. This was also justified by the sharp increase in the
      annual incidence of multiple sclerosis reported to the French health insurance in
      the mid-1990s. Almost 20 years later, a retrospective reflection can be sketched
      from these official data and also from the national pharmacovigilance agency.
      Statistical data from these latter sources seem to show a significant correlation
      between the number of hepatitis B vaccinations performed and the declaration to
      the pharmacovigilance of multiple sclerosis occurring between 1 and 2 years
      later. The application of the Hill's criteria to these data indicates that the
      correlation between hepatitis B vaccine and multiple sclerosis may be causal.

PMID- 25395339
TI  - Immunoreactivity and avidity of IgG anti-beta2-glycoprotein I antibodies from
      patients with autoimmune diseases to different peptide clusters of beta2
      glycoprotein I.
AB  - The pathogenicity of antibodies against beta2-glycoprotein I (anti-beta2GPI)
      depends on multiple factors such as subclass type, epitope binding and avidity.
      Due to their large heterogeneity, their impact on antiphospholipid syndrome (APS)
      onset is still not fully clarified. We studied the binding characteristics of IgG
      anti-beta2GPI with known avidity from sera of 201 autoimmune patients (87 with
      APS, 67 with APS associated with systemic lupus erythematosus (SLE), 47 with only
      SLE) to six beta2GPI peptides corresponding to amino acid clusters on domains I
      II, II, III and III-IV by indirect ELISA and evaluated their association with
      clinical features of APS. Peptides A (LKTPRV; domain I-II), B (KDKATF; domain IV)
      and C (TLRVYK; domain III) were derived from a hexapeptide phage display library
      previously shown to react with pathogenic monoclonal anti-beta2GPI. Peptides D
      (NGPANSK; domain III), E (YNPLWFV; domain II) and F (KMDGNHP; domain III-IV)
      represent surface amino acid clusters on beta2GPI. The percentage of patients
      positive for peptides were observed as follows: 30.3% for peptide D, 28.90% for
      B, 25.9% for C, 24.9% for E, 24.4% for F and 10.0% for A. The anti-peptide
      antibodies in studied serum samples were predominantly of heterogeneous avidity,
      followed by law avidity anti-peptide antibodies, whereas only a few were of high
      avidity. Positive and negative correlations were found between several anti
      peptide antibodies and the rate of thrombosis. Our results indicated diverse
      reactivity of IgG anti-beta2GPI to different epitopes on beta2GPI. Classification
      of IgG anti-beta2GPI into subgroups regarding epitope specificity and avidity
      could represent an additional tool in understanding their pathogenicity in APS.

PMID- 25395340
TI  - Autoimmune/inflammatory syndrome induced by adjuvants (ASIA): clues and pitfalls
      in the pediatric background.
AB  - The development and increasing diffusion of new vaccinations and global
      immunization protocols have aroused burning debates about safety of adjuvants and
      their immunogenicity-enhancing effect in vaccines. Shoenfeld and Agmon-Levin have
      grouped under the term "autoimmune/inflammatory syndrome induced by adjuvants"
      (ASIA) a complex of variable signs and symptoms that may occur after a previous
      exposure to different adjuvants and also external environmental triggers, even
      eliciting specific overt immune-mediated disorders. This entity subsumes five
      medical conditions: post-vaccination phenomena, gulf war syndrome, macrophagic
      myofasciitis syndrome, siliconosis, and sick building syndrome, but the relevance
      and magnitude of the syndrome in the pediatric age is fundamentally limited to
      post-vaccination autoimmune or inflammatory disorders. The occurrence of vaccine
      triggered phenomena represents a diagnostic challenge for clinicians and a
      research conundrum for many investigators. In this paper, we will analyze the
      general features of ASIA and focus on specific post-vaccination events in
      relation with the pediatric background. In the presence of a favorable genetic
      background, many autoimmune/inflammatory responses can be triggered by adjuvants
      and external factors, showing how the man himself might breach immune tolerance
      and drive many pathogenetic aspects of human diseases. Nonetheless, the elective
      application of ASIA diagnostic criteria to the pediatric population requires
      further assessment and evaluations. Additional studies are needed to help clarify
      connections between innate or adaptive immunity and pathological and/or
      protective autoantibodies mostly in the pediatric age, as children and
      adolescents are mainly involved in the immunization agendas related to vaccine
      preventable diseases.

PMID- 25395341
TI  - The sera from adult patients with suggestive signs of autoimmune diseases present
      antinuclear autoantibodies that cross-react with Leishmania infantum conserved
      proteins: crude Leishmania histone and Soluble Leishmania antigens [corrected].
AB  - Visceral leishmaniasis has been associated with hyper-gammaglobulinemia and
      antinuclear antibodies and may simulate systemic lupus erythematosus. Sera from
      patients with visceral leishmaniasis have been shown to strongly react against
      conserved proteins from the parasite, such as ribosomal and histones. Some of
      these proteins have also been described as immunogenic in several auto-immune
      syndromes, and the detection of antibodies against them is considered to be
      indicative of disorder in the immune system. This study aimed to assess by enzyme
      linked immunosorbent assay, test routinely employed in visceral leishmaniasis
      diagnosis, the recognition of Crude Leishmania histone and Soluble Leishmania
      antigens proteins from Leishmania infantum by adult patients with suggestive
      signs of autoimmune diseases. Our results show that the humoral response
      generated during autoimmune diseases cross-reacts with the parasitic Crude
      Leishmania histone and Soluble Leishmania antigens. In these cases, higher
      precautions must be taken to confirm the presence of visceral leishmaniasis in
      front of positive serology in antinuclear antibodies positive sera, in order to
      avoid wrong diagnosis. 

PMID- 25395342
TI  - Metabolic syndrome and its relationship with the achievement of minimal disease
      activity state in psoriatic arthritis patients: an observational study.
AB  - The aim of the study was to evaluate the influence of metabolic syndrome (MetS)
      on achieving minimal disease activity (MDA) in psoriatic arthritis (PsA) patients
      treated with anti-tumor necrosis factor (TNF)-alpha with a follow-up period of 24
      months. A cohort of PsA patients was assessed at the University Federico II of
      Naples and at University of Padova. For the aim of the present study, patients'
      data were collected at baseline (T0), at 12 months (T1) and at 24 months (T2).
      Assessment of metabolic and disease activity parameters was performed at each
      visit. The NCEP-ACT III criteria were used to identify subjects with MetS and the
      MDA criteria to evaluate the disease activity. On the basis of the exclusion and
      inclusion criteria, 330 subjects were included in the study; 134 patients (40.7%)
      were classified as not having MetS and 196 (59.3%) as having MetS. An inverse
      association was found between presence of metabolic syndrome and the probability
      of achieving MDA. Univariate analysis indicated that patients with metabolic
      syndrome were less likely to achieve MDA than patients without metabolic syndrome
      (OR 0.45, p < 0.001). This inverse association remained statistically significant
      in the multivariate regression model (OR 0.56, p < 0.001). Metabolic syndrome is
      associated with a lower probability of achieving MDA in PsA patients in therapy
      with anti-TNF-alpha.

PMID- 25395344
TI  - Modelling in anaesthesia and intensive care: a special section including papers
      from IFAC's 8. Symposium on Medical and Biological Systems in Budapest 2012.

PMID- 25395345
TI  - Staying on Task: Age-Related Changes in the Relationship Between Executive
      Functioning and Response Time Consistency.
AB  - OBJECTIVE: Little is known about the relationship of executive functioning with
      age-related increases in response time (RT) distribution indices (intraindividual
      standard deviation [ISD], and ex-Gaussian parameters mu, sigma, tau). The goals
      of this study were to (a) replicate findings of age-related changes in response
      time distribution indices during an engaging touch-screen RT task and (b)
      investigate age-related changes in the relationship between executive functioning
      and RT distribution indices. METHOD: Healthy adults (24 young [aged 18-30], 24
      young-old [aged 65-74], and 24 old-old [aged 75-85]) completed a touch-screen
      attention task and a battery of neuropsychological tests. The relationships
      between RT performance and executive functions were examined with structural
      equation modeling (SEM). RESULTS: ISD, mu, and tau, but not sigma, increased with
      age. SEM revealed tau as the most salient RT index associated with
      neuropsychological measures of executive functioning. Further analysis
      demonstrated that correlations between tau and a weighted executive function
      composite were significant only in the old-old group. DISCUSSION: Our results
      replicate findings of greater RT inconsistency in older adults and reveal that
      executive functioning is related to tau in adults aged 75-85. These results
      support literature identifying tau as a marker of cognitive control, which
      deteriorates in old age.

PMID- 25395343
TI  - Drug-induced acute kidney injury in children.
AB  - Acute kidney injury (AKI) is a serious problem occurring in anywhere between 8
      and 30% of children in the intensive care unit. Up to 25% of these cases are
      believed to be the result of pharmacotherapy. In this review we have focused on
      several relevant drugs and/or drug classes, which are known to cause AKI in
      children, including cancer chemotherapeutics, non-steroidal anti-inflammatory
      drugs and antimicrobials. AKI demonstrates a steady association with increased
      long term risk of poor outcomes including chronic kidney disease and death as
      determined by the extent of injury. For this reason it is important to understand
      the causality and implications of these drugs and drug classes. Children occupy a
      unique patient population, advocating the importance of understanding how they
      are affected dissimilarly compared with adults. While the kidney itself is likely
      more susceptible to injury than other organs, the inherent toxicity of these
      drugs also plays a major role in the resulting AKI. Mechanisms involved in the
      toxicity of these drugs include oxidative damage, hypersensitivity reactions,
      altered haemodynamics and tubule obstruction and may affect the glomerulus and/or
      the tubules. Understanding these mechanisms is critical in determining the most
      effective strategies for treatment and/or prevention, whether these strategies
      are less toxic versions of the same drugs or add-on agents to mitigate the toxic
      effect of the existing therapy. 

PMID- 25395346
TI  - Mexico's "ley de narcomenudeo" drug policy reform and the international drug
      control regime.
AB  - It has been over half a century since the landmark Single Convention on Narcotic
      Drugs was adopted, for the first time unifying international drug policy under a
      single treaty aimed at limiting use, manufacture, trade, possession, and
      trafficking of opiates, cannabis, and other narcotics. Since then, other
      international drug policy measures have been adopted, largely emphasizing
      enforcement-based approaches to reducing drug supply and use. Recently, in
      response to concerns that the historic focus on criminalization and enforcement
      has had limited effectiveness, international drug policies have begun to undergo
      a paradigm shift as countries seek to enact their own reforms to partially
      depenalize or deregulate personal drug use and possession. This includes Mexico,
      which in 2009 enacted national drug policy reform partially decriminalizing
      possession of small quantities of narcotics for personal consumption while also
      requiring drug treatment for repeat offenders. As countries move forward with
      their own reform models, critical assessment of their legal compatibility and
      effectiveness is necessary. In this commentary we conduct a critical assessment
      of the compatibility of Mexico's reform policy to the international drug policy
      regime and describe its role in the current evolving drug policy environment. We
      argue that Mexico's reform is consistent with flexibilities allowed under
      international drug treaty instruments and related commentaries. We also advocate
      that drug policy reforms and future governance efforts should be based on
      empirical evidence, emphasize harm reduction practices, and integrate evidence
      based evaluation and implementation of drug reform measures. 

PMID- 25395348
TI  - Nationwide collaborative development of learning outcomes and exemplar standards
      for Australian pharmacy programmes.
AB  - OBJECTIVES: Internationally, the preparation of pharmacy graduates for
      professional practice has evolved from educating for capacities for practice, to
      a focus on competencies, and most recently, on assuring graduate outcomes.
      Consequently, there is an increasing emphasis on the specification of and
      accountability around student learning outcomes. This, in turn, has implications
      for teaching and assessment. The aim of the study was to harmonise the various
      expectations and regulatory requirements for Australian pharmacy education
      programmes through the development of learning outcomes and exemplar standards
      for all entry-level pharmacy graduates. METHODS: Learning outcomes and exemplar
      standards were developed through a participatory action research framework which
      involved academic staff representatives from pharmacy schools in Australia,
      pharmacy student representatives, and the Australian Pharmacy Council (APC, the
      accreditation body for Australian pharmacy programs) involving an iterative
      process of dissemination and seeking of feedback. KEY FINDINGS: The key result
      from the project was the formulation of national pharmacy learning outcomes and
      exemplar standards (PhLOS) for all students graduating from entry-level pharmacy
      programmes. These have been endorsed by both students and academics. CONCLUSIONS:
      Learning outcomes have been developed through a collaborative process for
      pharmacy programmes across Australia through harmonisation of the various
      expectations and regulatory requirements for pharmacy education programmes.
      Application of these learning outcomes and exemplar standards will ensure that
      all graduates of all entry-level pharmacy programmes will have achieved at least
      the same threshold, regardless of the university from which they graduate prior
      to entering their internship year.

PMID- 25395347
TI  - A case-control study on oral health-related quality of life in kidney disease
      patients undergoing haemodialysis.
AB  - OBJECTIVE: The study aims to assess the influence of oral health status and socio
      behavioural variables on oral health-related quality of life (OHRQoL) in a sample
      of Iranian haemodialysis (HD) patients. MATERIALS AND METHODS: The present case
      control study included 512 patients undergoing HD and 255 healthy controls from
      Iran. A self-reported questionnaire was used to record socio-demographic
      variables. In addition, laboratory and clinical variables of each patient were
      extracted from clinical and patient's electronic records. A closed-ended
      questionnaire was framed in order to assess oral health knowledge, attitudes and
      behaviour of each subject. The Short Form Health Survey (SF-36) and Oral Health
      Impact Profile-14 (OHIP-14) were used respectively to assess general health
      related quality of life (GHRQoL) and OHRQoL. All subjects were clinically
      examined by two trained and experienced dentists for caries by decayed, missing
      and filled teeth index (DMFT), dental plaque by visible plaque index (VPI),
      gingival status by Loe and Silness gingival index (GI) and periodontal status by
      community periodontal index (CPI). RESULTS: Statistically significant differences
      were found between HD patients and control subjects for all oral health indices.
      Patients had significantly (p < 0.001) higher mean DMFT, VPI and GI values than
      controls. Periodontal pockets deeper than 4 mm were more frequently diagnosed in
      HD patients (p < 0.001). HD patients reported significantly poorer GHRQoL and
      also a higher impact of oral health (i.e. poorer OHRQoL) in comparison with the
      healthy controls (p < 0.01). CONCLUSIONS: Oral health status, clinical variables,
      socio-behavioural factors and GHRQoL were significant predictors of OHRQoL in
      Iranian HD patients. CLINICAL RELEVANCE: The study findings support the
      assumption that patient-reported measures can be used to predict treatment need
      since the objective clinical variables were significantly related to subjective
      self-reported quality of life in HD patients.

PMID- 25395349
TI  - Adherence and medication utilisation patterns of fixed-dose and free combination
      of angiotensin receptor blocker/thiazide diuretics among newly diagnosed
      hypertensive patients: a population-based cohort study.
AB  - OBJECTIVE: The study aimed to compare the adherence and persistence among newly
      diagnosed hypertensive patients using fixed-dose (FDC) and free combinations (FC)
      of angiotensin receptor blocker (ARB)/thiazide diuretic using Taiwan's National
      Health Insurance Research Database. METHODS: General linear regression and Kaplan
      Meier analyses were used to estimate the impact of FDC on adherence [measured by
      medication possession ratio (MPR)] and persistence (time from day of initiation
      to treatment discontinuation) of ARB/thiazide diuretic. RESULTS: The adjusted
      MPRs were all significantly higher among FDC group compared with FC group (6
      months: 66.55% vs. 63.86%; 1 year: 52.58% vs. 46.73%, 1.5 year: 46.30% vs.
      38.07%; 2 year: 42.06% vs. 32.45%, all p < 0.001). Patients received FDC therapy
      were less likely to discontinue their therapy [adjusted hazard ratio (HR) 0.79,
      95% CI = 0.74-0.85]. CONCLUSIONS: Our findings suggest that use of FDC is
      associated with higher adherence and persistence rates than use of FC in newly
      diagnosed hypertensive patients.

PMID- 25395352
TI  - Cinderella finds her shoe: the first Vps34 inhibitor uncovers a new PI3K-AGC
      protein kinase connection.
AB  - Class II/III PI3Ks (phosphoinositide 3-kinases) produce the PtdIns(3)P lipid that
      is involved in intracellular vesicular trafficking. In contrast with class I
      PI3Ks, the potential signalling roles of class II/III PI3Ks are poorly
      understood. In a recent article in the Biochemical Journal, Bago and co-workers
      report that Vps34 (vacuolar protein sorting 34), the only class III PI3K,
      controls the activity of SGK3 (serum- and glucocorticoid-regulated protein kinase
      3). Like other AGC kinases, the SGKs (SGK1, SGK2 and SGK3) are activated by dual
      phosphorylation. Unlike its cousins SGK1 and SGK2, SGK3 contains a PtdIns(3)P
      binding domain, providing an additional element of regulation. The study by Bago
      et al. characterizes and makes extensive use of a Novartis Vps34 inhibitor (VPS34
      IN1) that inhibits this PI3K isoform with nanomolar potency, without affecting
      other lipid kinases or more than 300 protein kinases. The authors show that this
      compound very rapidly reduced PtdIns(3)P levels at the endosome with concomitant
      loss of SGK3 phosphorylation. Co-inhibition of class I PI3Ks led to a further
      reduction in SGK3 activity, indicating that class I PI3Ks may also regulate SGK3
      activity through an additional, currently unknown, mechanism. It remains to be
      assessed whether the novel PI3K-protein kinase connection established by this
      study is subject to acute cellular stimulation or is part of a constitutive
      housekeeping function. VPS34-IN1 will provide a useful tool to decipher the
      kinase-dependent functions of Vps34, with acute changes in SGK3 phosphorylation
      and subcellular localization being new biomarkers of Vps34 activity. 

PMID- 25395350
TI  - Postprandial glucose, insulin and incretin responses to different carbohydrate
      tolerance tests.
AB  - BACKGROUND: Few studies have focused on postprandial incretin responses to
      different carbohydrate meals. Therefore, we designed a study to compare the
      different effects of two carbohydrates (75 g oral glucose, a monosaccharide and
      100 g standard noodle, a polysaccharide, with 75 g carbohydrates equivalently) on
      postprandial glucose, insulin and incretin responses in different glucose
      tolerance groups. METHODS: This study was an open-label, randomized, two-way
      crossover clinical trial. 240 participants were assigned to take two
      carbohydrates in a randomized order separated by a washout period of 5-7 days.
      The plasma glucose, insulin, c-peptide, glucagon and active glucagon-like peptide
      1 (AGLP-1) were measured. The incremental area under curve above baseline from 0
      to 120 min of insulin (iAUC(0 -120 min)- INS) and AGLP-1(iAUC(0 -120 min)- AGLP
      1) was calculated. RESULTS: Compared with standard noodles, the plasma glucose
      and insulin after consumption of oral glucose were higher at 30 min (both P <
      0.001) and 60 min (both P < 0.001), while lower at 180 min (both P < 0.001), but
      no differences were found at 120 min. The glucagon at 180 min was higher after
      consumption of oral glucose (P = 0.010). The AGLP-1 response to oral glucose was
      higher at 30 min (P < 0.001), 60 min (P < 0.001) and 120 min (P = 0.022), but
      lower at 180 min (P = 0.027). In normal glucose tolerance (NGT), oral glucose
      elicited a higher insulin response to the corresponding AGLP-1 (P < 0.001), which
      was represented by iAUC(0 -120 min) -INS /iAUC(0 -120 min)- AGLP-1, while in type
      2 diabetes mellitus (T2DM), standard noodles did (P = 0.001). CONCLUSIONS:
      Monosaccharide potentiated more rapid and higher glycemic and insulin responses.
      Oral glucose of liquid state would elicit a more potent release of AGLP-1. The
      incretin effect was amplified after consumption of standard noodles in T2DM.

PMID- 25395353
TI  - Learning about solubility.
AB  - Qualitative questions are proposed to assess the understanding of solubility and
      some of its applications. To improve those results, a simple quantitative problem
      on the precipitation of proteins is proposed.

PMID- 25395354
TI  - Reduced content of chloroatranol and atranol in oak moss absolute significantly
      reduces the elicitation potential of this fragrance material.
AB  - BACKGROUND: Oak moss absolute, an extract from the lichen Evernia prunastri, is a
      valued perfume ingredient but contains extreme allergens. OBJECTIVES: To compare
      the elicitation properties of two preparations of oak moss absolute: 'classic oak
      moss', the historically used preparation, and 'new oak moss', with reduced
      contents of the major allergens atranol and chloroatranol.
      PATIENTS/MATERIALS/METHODS: The two preparations were compared in randomized
      double-blinded repeated open application tests and serial dilution patch tests in
      30 oak moss-sensitive volunteers and 30 non-allergic control subjects. RESULTS:
      In both test models, new oak moss elicited significantly less allergic contact
      dermatitis in oak moss-sensitive subjects than classic oak moss. The control
      subjects did not react to either of the preparations. CONCLUSIONS: New oak moss
      is still a fragrance allergen, but elicits less allergic contact dermatitis in
      previously oak moss-sensitized individuals, suggesting that new oak moss is less
      allergenic to non-sensitized individuals.

PMID- 25395355
TI  - Incremental cost-effectiveness of dobutamine stress cardiac magnetic resonance
      imaging in patients at intermediate risk for coronary artery disease.
AB  - AIMS: The effectiveness of stress cardiac magnetic resonance (CMR) as a
      gatekeeper for coronary angiography (CA) has been established. Level five HTA
      studies according to the hierarchical model of diagnostic test evaluation are not
      available. METHODS: This cohort study included 1,158 consecutive patients (mean
      age 63 +/- 11 years, 42 % women) presenting at our institution between January 1,
      2003 and December 31, 2004 with suspected coronary artery disease (CAD) for an
      elective CA. The patients were assessed for eligibility and propensity score
      matching was applied to address selection bias regarding the patients' allocation
      to CMR or direct CA. Median patient follow-up was 7.9 years (95 % CI 7.8-8.0
      years). The primary effect was calculated as relative survival difference. The
      cost unit calculation (per patient) at our institute was the source of costs.
      RESULTS: Survival was similar in CMR and CA (p = 0.139). Catheterizations ruling
      out CAD were significantly reduced by the CMR gate-keeper strategy. Patients with
      prior CMR had significantly lower costs at the initial hospital stay and at
      follow-up (CMR vs. CA, initial: 2,904<euro> vs. 3,421<euro>, p = 0.018; follow
      up: 2,045<euro> vs. 3,318<euro>, p = 0.037). CMR was cost-effective in terms of a
      contribution of 12,466<euro> per life year to cover a part of the CMR costs.
      CONCLUSION: Stress CMR prior to CA was saving 12,466<euro> of hospital costs per
      life year. Lower costs at follow-up suggest sustained cost-effectiveness of the
      CMR-guided strategy.

PMID- 25395356
TI  - The discovery of a highly selective 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3
      d]pyrimidin-4(3H)-one SIRT2 inhibitor that is neuroprotective in an in vitro
      Parkinson's disease model.
AB  - Sirtuins, NAD(+) -dependent histone deacetylases (HDACs), have recently emerged
      as potential therapeutic targets for the treatment of a variety of diseases. The
      discovery of potent and isoform-selective inhibitors of this enzyme family should
      provide chemical tools to help determine the roles of these targets and validate
      their therapeutic value. Herein, we report the discovery of a novel class of
      highly selective SIRT2 inhibitors, identified by pharmacophore screening. We
      report the identification and validation of 3-((2-methoxynaphthalen-1-yl)methyl)
      7-((pyridin-3-ylmethyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin
      4(3H)-one (ICL-SIRT078), a substrate-competitive SIRT2 inhibitor with a Ki value
      of 0.62 +/- 0.15 MUM and more than 50-fold selectivity against SIRT1, 3 and 5.
      Treatment of MCF-7 breast cancer cells with ICL-SIRT078 results in
      hyperacetylation of alpha-tubulin, an established SIRT2 biomarker, at doses
      comparable with the biochemical IC50 data, while suppressing MCF-7 proliferation
      at higher concentrations. In concordance with the recent reports that suggest
      SIRT2 inhibition is a potential strategy for the treatment of Parkinson's
      disease, we find that compound ICL-SIRT078 has a significant neuroprotective
      effect in a lactacystin-induced model of Parkinsonian neuronal cell death in the
      N27 cell line. These results encourage further investigation into the effects of
      ICL-SIRT078, or an optimised derivative thereof, as a candidate neuroprotective
      agent in in vivo models of Parkinson's disease.

PMID- 25395357
TI  - Beyond Watches and Chocolate-Global Mental Health Elective in Switzerland.
AB  - Despite increasing interest in global mental health training opportunities, only
      a few psychiatry residency programs offer global mental health training
      experiences in developing countries and even fewer programs offer it in other
      first-world countries. The authors developed a global mental health elective
      giving US psychiatry residents the opportunity to visit Switzerland to study and
      experience the mental health care system in this European country. This elective
      focuses on four major learning objectives: (1) the system of training and
      curriculum of postgraduate psychiatry education in Switzerland, (2) clinical and
      organizational aspects of Swiss mental health, (3) administrative aspects of
      Swiss mental health care delivery, and (4) scholarly activity. This program was
      uniquely tailored for psychiatry residents. The preliminary experiences with US
      psychiatry residents show that they value this learning experience, the
      opportunity to access a different mental health care system, as well as the
      potential to build international connections with peers. 

PMID- 25395358
TI  - Evaluation of hypericin: effect of aggregation on targeting biodistribution.
AB  - Hypericin (Hy) has shown great promise as a necrosis-avid agent in cancer imaging
      and therapy. Given the highly hydrophobic and pi-conjugated planarity
      characteristics, Hy tends to form aggregates. To investigate the effect of
      aggregation on targeting biodistribution, nonaggregated formulation (Non-Ag),
      aggregated formulation with overconcentrated Hy in dimethyl sulfoxide (Ag-DMSO)
      solution, and aggregated formulation in water solution (Ag-water) were selected
      by fluorescence measurement. They were labeled with 131I and evaluated for the
      necrosis affinity in rat model of reperfused hepatic infarction by gamma counting
      and autoradiography. The radioactivity ratio of necrotic liver/normal liver was
      17.1, 7.9, and 6.4 for Non-Ag, Ag-DMSO, and Ag-water, respectively. The
      accumulation of two aggregated formulations (Ag-DMSO and Ag-water) in organs of
      mononuclear phagocyte system (MPS) was 2.62 +/- 0.22 and 3.96 +/- 0.30 %ID/g in
      the lung, and 1.44 +/- 0.29 and 1.51 +/- 0.23 %ID/g in the spleen, respectively.
      The biodistribution detected by autoradiography showed the same trend as by gamma
      counting. In conclusion, the Non-Ag showed better targeting biodistribution and
      less accumulation in MPS organs than aggregated formulations of Hy. The two
      aggregated formulations showed significantly lower and higher accumulation in
      targeting organ and MPS organs, respectively.

PMID- 25395359
TI  - Hepatic insulin resistance in ob/ob mice involves increases in ceramide, aPKC
      activity, and selective impairment of Akt-dependent FoxO1 phosphorylation.
AB  - Pathogenesis of insulin resistance in leptin-deficient ob/ob mice is obscure. In
      another form of diet-dependent obesity, high-fat-fed mice, hepatic insulin
      resistance involves ceramide-induced activation of atypical protein kinase C
      (aPKC), which selectively impairs protein kinase B (Akt)-dependent forkhead box
      O1 protein (FoxO1) phosphorylation on scaffolding protein, 40 kDa WD(tryp-x-x
      asp)-repeat propeller/FYVE protein (WD40/ProF), thereby increasing
      gluconeogenesis. Resultant hyperinsulinemia activates hepatic Akt and mammalian
      target of rapamycin C1, and further activates aPKC; consequently, lipogenic
      enzyme expression increases, and insulin signaling in muscle is secondarily
      impaired. Here, in obese minimally-diabetic ob/ob mice, hepatic ceramide and aPKC
      activity and its association with WD40/ProF were increased. Hepatic Akt activity
      was also increased, but Akt associated with WD40/ProF was diminished and
      accounted for reduced FoxO1 phosphorylation and increased gluconeogenic enzyme
      expression. Most importantly, liver-selective inhibition of aPKC decreased aPKC
      and increased Akt association with WD40/ProF, thereby restoring FoxO1
      phosphorylation and reducing gluconeogenic enzyme expression. Additionally,
      lipogenic enzyme expression diminished, and insulin signaling in muscle, glucose
      tolerance, obesity, hepatosteatosis, and hyperlipidemia improved. In conclusion,
      hepatic ceramide accumulates in response to CNS-dependent dietary excess
      irrespective of fat content; hepatic insulin resistance is prominent in ob/ob
      mice and involves aPKC-dependent displacement of Akt fromWD40/ProF and subsequent
      impairment of FoxO1 phosphorylation and increased expression of hepatic
      gluconeogenic and lipogenic enzymes; and hepatic alterations diminish insulin
      signaling in muscle. 

PMID- 25395360
TI  - Chronic kidney disease in disadvantaged populations.
AB  - The increased burden of CKD in disadvantaged populations is due to both global
      factors and population-specific issues. Low socioeconomic status and poor access
      to care contribute to healthcare disparities and exacerbate the negative effects
      of genetic or biologic predisposition. Provision of appropriate renal care to
      these populations requires a two-pronged approach: expanding the reach of
      dialysis through development of low-cost alternatives that can be practiced in
      remote locations, and implementation and evaluation of cost-effective prevention
      strategies. Kidney transplantation should be promoted by expanding both deceased
      donor transplant programs and the use of inexpensive, generic immunosuppressive
      drugs. The message of WKD 2015 is that a concerted attack against the diseases
      that lead to ESRD, by increasing community outreach, better education, improved
      economic opportunity, and access to preventive medicine for those at highest
      risk, could end the unacceptable relationship between CKD and disadvantage in
      these communities.

PMID- 25395361
TI  - C3 nephritic factor can be associated with membranous glomerulonephritis.
AB  - BACKGROUND: C3 nephritic factor (C3NeF) has been described in association with
      membranoproliferative glomerulonephritis and is involved in 80 % of cases of
      dense deposit disease. C3NeF is an immunoglobulin G (IgG) autoantibody which
      binds to the complement component 3 (C3) convertase C3bBb, thereby inhibiting its
      decay and leading to massive C3 cleavage. Commonly associated with C3NeF are low
      C3 levels, decreased total haemolytic complement (CH50) and normal C4 levels.
      C3NeF patients often present with proteinuria, haematuria and high blood
      pressure. Evolution to end-stage renal disease is common. Treatment consists of
      steroids and/or immunosuppressants, with variable efficiency. Renal
      transplantation is marked by histological recurrence, leading to higher rates of
      allograft loss. CASES: We report C3NeF in association with membranous
      glomerulonephritis type 3-4 in two unrelated children. We also demonstrate that,
      under adequate immunosuppressive therapy, proteinuria is significantly lowered,
      blood pressure is kept within normal range and long-term renal function remains
      normal. CONCLUSIONS: C3NeF can be associated with membranous glomerulonephritis
      in children. Clinical presentation is mild, and mid-term outcome is favourable
      under adequate therapy. However, complement anomalies persist for several years.

PMID- 25395362
TI  - Interdialytic weight gain in oligoanuric children and adolescents on chronic
      hemodialysis.
AB  - BACKGROUND: Little is known about the clinical impact of interdialytic weight
      gain (IDWG) on oligoanuric children undergoing chronic hemodialysis (HD).
      METHODS: We retrospectively assessed IDWG, left ventricular mass index (LVMI) and
      its changes (DeltaLVMI), pre-HD systolic and diastolic blood pressure (DBP),
      residual urine output, Kt/V, the frequency of intradialytic symptoms, normalized
      protein catabolic rate, and the 3-month change in the dry weight of 16
      hemodialyzed oligoanuric patients with a median age of 14.8 years (range 5.0
      17.9). RESULTS: There was a significant correlation between IDWG and median LVMI
      (r 0.55, p = 0.026), which was 27.3 g/m(2.7) (22.5-37.6) in the patients with a
      median IDWG of <4 %, and 44.3 g/m(2.7) (28.2-68.7) in those with a median IDWG of
      >4 % (p = 0.003). None of the four patients with an IDWG of <4 % showed left
      ventricular hypertrophy, compared with 10 of the 12 patients (83.3 %) with an
      IDWG of >4 % (p = 0.003); the former also had a better median DeltaLVMI (-33.5 %
      vs -13.0 %; p = 0.02) and a lower median DBP sds (0.24 vs 1.72, p = 0.04).
      CONCLUSIONS: There is a significant correlation between IDWG and LVMI in
      pediatric oligoanuric patients on chronic HD: those with an IDWG of >4 % are at a
      higher risk of left ventricular hypertrophy.

PMID- 25395363
TI  - First-trimester combined screening for trisomy 21 in women with renal disease.
AB  - OBJECTIVE: To evaluate the results of first-trimester combined screening for Down
      syndrome in women with chronic renal disease. METHOD: Fifty-five pregnant women
      with renal disease were compared with 110 patients matched for maternal age,
      maternal weight, smoking status, and gestational age. Maternal renal function was
      assayed at the time of the combined screening, and renal insufficiency was
      defined by serum creatinine >90 umol/L and renal clearance <80 mL/min. We defined
      three groups: kidney disease and normal renal function (group 1), kidney disease
      and renal insufficiency (group 2), and a control group (group 3). The values of
      nuchal translucency, pregnancy-associated plasma protein A, human beta-chorionic
      gonadotrophin (hCGbeta), and false-positive rates for Down syndrome screening
      were compared. RESULTS: There were 39 (71%) and 16 (29%) cases in groups 1 and 2,
      respectively. Nuchal translucency and multiple of the median (MoM) pregnancy
      associated plasma protein A were similar in the three groups. However, MoM
      hCGbeta levels were higher in group 2 than in groups 1 and 3 (5.37 vs 1.1 vs 0.98
      MoM, p = 0.0001). The resulting screen-positive rate was also higher in group 2
      than in groups 1 and 3 (43.7% vs 10.2% vs 5.5%, p = 0.0001). CONCLUSION: Trisomy
      21 first-trimester screening using hCGbeta is not suitable in the case of
      maternal renal failure. (c) 2014 John Wiley & Sons, Ltd.

PMID- 25395364
TI  - Evaluation of IVOCT imaging of coronary artery metallic stents with neointimal
      coverage.
AB  - Accuracy of IVOCT for measurement of neointimal thickness and effect of neointima
      in the appearance of metallic struts in IVOCT images was investigated. Phantom
      vessels were constructed and coronary stents were deployed and covered with thick
      (250-400 MUm) and thin (30-70 MUm) phantom neointima. High resolution Micro-CT
      images of the stent struts were recorded as a gold standard. IVOCT images of the
      phantom vessels were acquired with various luminal blood scattering strengths and
      measured neointimal thicknesses from IVOCT and Micro-CT images were compared. In
      transparent lumen, comparison of IVOCT and Micro-CT neointima thickness
      measurements found no significant difference (p > 0.05) in the thick neointima
      phantom but a significant difference (p < 0.05) in the thin neointima phantom.
      For both thick and thin neointima, IVOCT neointimal thickness measurements varied
      from Micro-CT values by as much as +/-35%. Increased luminal scattering due to
      presence of blood at concentrations <5% did not interfere with measurement of
      thin neointimas and was validated by ANOVA analysis (p = 0.95). IV-OCT
      measurement of strut feature size with an overlying thin neointima match true
      values determined with Micro-CT (p = 0.82). Presence of a thick neointima
      resulted in lateral elongation or merry-go-rounding of stent strut features in
      IVOCT images. Phantom IVOCT images suggest that thick neointimal layers can
      result in more than 40 % lateral elongation of stent strut features. Simulated
      IVOCT images of metallic stent struts with varying neointimal thickness suggest
      that neointimal light scattering can introduce the merry-go-round effect.

PMID- 25395365
TI  - The association of pre-pregnancy alcohol drinking with child neuropsychological
      functioning.
AB  - OBJECTIVE: To examine the effects of pre-pregnancy alcohol drinking on child
      neuropsychological functioning. DESIGN: Prospective follow-up study. SETTING AND
      POPULATION: 154 women and their children sampled from the Danish National Birth
      Cohort. METHODS: Participants were sampled based on maternal alcohol consumption
      before pregnancy. At 5 years of age, the children were tested with the Wechsler
      Preschool and Primary Scale of Intelligence-Revised, the Test of Everyday
      Attention for Children at Five (TEACh-5), and the Movement Assessment Battery for
      Children (MABC). The Behaviour Rating Inventory of Executive Function (BRIEF) was
      completed by the mothers and a preschool teacher. Parental education, maternal
      IQ, prenatal maternal smoking, child's age at testing, child's sex, and maternal
      alcohol intake during pregnancy were considered potential confounders. MAIN
      OUTCOME MEASURES: Performance on the Wechsler Preschool and Primary Scale of
      Intelligence-Revised, the TEACh-5, the MABC, and the BRIEF. RESULTS: Intake of 15
      21 drinks/week on average prior to pregnancy was not associated with any of the
      outcomes, but intake of >=22 drinks/week on average was associated with a
      significantly lower adjusted mean full scale IQ and lower adjusted means in
      overall attention and sustained attention score, but not in selective attention
      score or any of the BRIEF index scores or MABC scores. CONCLUSIONS: Intake of
      >=22 drinks/week before pregnancy was associated with lower mean full scale IQ,
      overall attention and sustained attention. Assessment of pre-pregnancy drinking
      provides additional information regarding potential prenatal alcohol exposure and
      its implications for child neurodevelopment.

PMID- 25395371
TI  - Comparison of Systemic Toxicity between Botulinum Toxin Subtypes A1 and A2 in
      Mice and Rats.
AB  - The adverse events caused by botulinum toxin type A (subtype A1) product, thought
      to be after-effects of toxin diffusion after high-dose administration, have
      become serious issues. A preparation showing less diffusion in the body than
      existing drugs has been sought. We have attempted to produce neurotoxin derived
      from subtype A2 (A2NTX) with an amino acid sequence different from that of
      neurotoxin derived from subtype A1 (A1NTX). In this study, to investigate whether
      A2NTX has the potential to resolve these issues, we compared the safety of A2NTX,
      a progenitor toxin derived from subtype A1 (A1 progenitor toxin) and A1NTX
      employing the intramuscular lethal dose 50% (im LD50) in mice and rats and the
      compound muscle action potential (CMAP) in rats. Mouse im LD50 values for A1
      progenitor toxin and A2NTX were 93 and 166 U/kg, respectively, and the rat im
      LD50 values were 117 and 153 U/kg, respectively. In the rat CMAP test, the dose
      on the contralateral side, which caused a 50% reduction in the CMAP amplitude,
      that is, CMAP-TD50 , was calculated as 19.0, 16.6 and 28.7 U/kg for A1 progenitor
      toxin, A1NTX and A2NTX, respectively. The results indicate that A2NTX is safer
      than A1 progenitor toxin and A1NTX.

PMID- 25395366
TI  - Targeted delivery of siRNA using transferrin-coupled lipoplexes specifically
      sensitizes CD71 high expressing malignant cells to antibody-mediated complement
      attack.
AB  - The overexpression of membrane-bound complement regulatory proteins (mCRP; CD46,
      CD55, CD59) preventing opsonization and complement-dependent cytotoxicity (CDC)
      is considered a major barrier for successful antibody-based cancer immunotherapy.
      To avoid a potential deleterious effect of mCRP neutralization on normal tissue
      cells, complement regulation has to be selectively targeted to the malignant
      cells. In this study, anti-mCRP small interfering RNAs (siRNAs) were encapsulated
      in transferrin-coupled lipoplexes for the specific delivery to transferrin
      receptor CD71(high) expressing BT474, DU145, and SW480 as well as corresponding
      CD71-knockdown (CD71(low)) tumor cells. Targeted delivery with transferrin-siRNA
      lipoplexes became possible by charge neutralization and resulted in efficient
      silencing of all three mCRPs up to 90%, which is dependent on their CD71
      expression. The mCRP knockdown led to a significant increase of CDC on CD71(high)
      tumor cells by 68% in BT474, 58% in DU145, and 40% in SW480 cells but only
      slightly increased on CD71(low) cells. Downregulation of CD46 and CD55
      significantly increased C3 opsonization only on CD71(high) tumor cells. Our
      results demonstrate for the first time that by specific delivery of anti-mCRP
      siRNA through transferrin receptor, complement regulation can be selectively
      neutralized, allowing specific antibody-mediated killing of tumor cells without
      affecting healthy bystander cells, which appears to be a suited strategy to
      improve antibody-based cancer immunotherapy.

PMID- 25395372
TI  - Accommodation Decision Making for Postsecondary Students With Learning
      Disabilities: Individually Tailored or One Size Fits All?
AB  - Clinicians uniformly recommend accommodations for college students with learning
      disabilities; however, we know very little about which accommodations they select
      and the validity of their recommendations. We examined the assessment
      documentation of a large sample of community college students receiving academic
      accommodations for learning disabilities to determine (a) which accommodations
      their clinicians recommended and (b) whether clinicians' recommendations were
      supported by objective data gathered during the assessment process. In addition
      to test and instructional accommodations, many clinicians recommended that
      students with learning disabilities should have different educational
      expectations, standards, and methods of evaluation (i.e., grading) than their
      nondisabled classmates. Many of their recommendations for accommodations were not
      supported by objective evidence from students' history, diagnosis, test data, and
      current functioning. Furthermore, clinicians often recommended accommodations
      that were not specific to the student's diagnosis or area of disability. Our
      findings highlight the need for individually selected accommodations matched to
      students' needs and academic contexts.

PMID- 25395373
TI  - Benzoxazolone carboxamides: potent and systemically active inhibitors of
      intracellular acid ceramidase.
AB  - The ceramides are a family of bioactive lipid-derived messengers involved in the
      control of cellular senescence, inflammation, and apoptosis. Ceramide hydrolysis
      by acid ceramidase (AC) stops the biological activity of these substances and
      influences survival and function of normal and neoplastic cells. Because of its
      central role in the ceramide metabolism, AC may offer a novel molecular target in
      disorders with dysfunctional ceramide-mediated signaling. Here, a class of
      benzoxazolone carboxamides is identified as the first potent and systemically
      active inhibitors of AC. Prototype members of this class inhibit AC with low
      nanomolar potency by covalent binding to the catalytic cysteine. Their metabolic
      stability and high in vivo efficacy suggest that these compounds may be used as
      probes to investigate the roles of ceramide in health and disease, and that this
      scaffold may represent a promising starting point for the development of novel
      therapeutic agents. 

PMID- 25395374
TI  - Comparative genomics of mycobacteria: some answers, yet more new questions.
AB  - Comparative genomic studies permit a genus-level perspective on the distinction
      between environmental mycobacteria and Mycobacterium tuberculosis, as well as a
      species-level assessment of genetic variability within M. tuberculosis. Both of
      these strata of evolutionary analysis serve to generate hypotheses regarding the
      genomic basis of M. tuberculosis virulence. In contrasting lessons from
      macroevolutionary study and microevolutionary study, one can form predictions
      about which segments of the genome are likely to be essential for or dispensable
      for the pathogenesis of tuberculosis. Although some of these predictions have
      been experimentally verified, notable exceptions challenge the direct link
      between these virulence factors and the capacity of M. tuberculosis to
      successfully cause disease and propagate between human hosts. These unexpected
      findings serve as the stimulus for further studies, using genomic comparisons and
      other approaches, to better define the remarkable success of this recalcitrant
      pathogen. 

PMID- 25395376
TI  - Patenting stem cell technologies in Europe.
AB  - European patent law as it applies to stem cell technologies is complex. The
      complexities have developed from different supranational sources of law during
      the last 50 years and from the various levels of exceptions to patentability
      embodied in the law. In relation to stem cells of human embryonic origin, the
      definition of a human embryo, although broad, is still in some respects unclear;
      and the definition of what constitutes the use of a human embryo for industrial
      or commercial purposes, which is excluded from patentability in Europe, is also
      remarkably broad. Further clarification is awaited from the courts and from the
      Boards of Appeal of the European Patent Office. 

PMID- 25395375
TI  - Gene therapy using stem cells.
AB  - Viral-mediated gene augmentation therapy has recently shown success in restoring
      vision to patients with retinal degenerative disorders. Key to this success was
      the availability of animal models that accurately presented the human phenotype
      to test preclinical efficacy and safety. These exciting studies support the use
      of gene therapy in the treatment of devastating retinal degenerative diseases. In
      some cases, however, in vivo gene therapy for retinal degeneration would not be
      effective because the cell types targeted are no longer present. The development
      of somatic cell reprogramming methods provides an attractive source of autologous
      cells for transplantation and treatment of retinal degenerative disease. This
      article explores the development of gene therapy and patient-derived stem cells
      for the purpose of restoring vision to individuals suffering from inherited
      retinal degenerations.

PMID- 25395377
TI  - Health-Related Quality of Life in Patients with MPS II.
AB  - Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a
      chronic and progressive X-linked lysosomal disease that mainly affects males. The
      National MPS Society (2013) reports that MPS II affects 1 in 100,000 to 1 in
      150,000 males worldwide. Two distinct forms of the disease are based on age of
      onset and clinical course: attenuated and severe. MPS II affects many organ
      systems including the nervous, cardiovascular, gastrointestinal and respiratory
      systems. Clinical manifestations can include progressive hearing loss, mental
      impairment, and enlarged liver and spleen. This study focuses on the health
      related quality of life of individuals (HRQOL) with MPS II as measured by the
      parent and self-report versions of the Pediatric Quality of Life Inventory
      (PedsQLTM). Both parents of patients with MPS II as well as patients themselves
      reported lower scores on all domains of the PedsQLTM (physical, emotional, social
      and school functioning) indicating that children with MPS II have an overall
      lower HRQOL when compared to a healthy sample. When compared with patients with
      other chronic illnesses (cancer, MSUD, galactosemia,), the MPS II sample had
      significantly lower scores on a number of PedsQLTM scales, suggesting an overall
      lower HRQOL. No significant relationships were found using scores from parent or
      self report PedsQLTM measures and length of time on ERT. 

PMID- 25395378
TI  - A randomized phase II study of everolimus for advanced pancreatic neuroendocrine
      tumors in Chinese patients.
AB  - Everolimus, an oral inhibitor of mammalian target of mTOR, has been recently
      shown to have antitumor effect in a phase III, double-blind, randomized trial
      (RADIANT-3) of 410 patients with advanced pancreatic neuroendocrine tumors
      (PNETs). The purpose of this study was to investigate the specific efficacy and
      safety of everolimus in the Chinese patient with PNETs. In this randomized phase
      II study, the analysis on Chinese patients was performed comparing efficacy and
      safety between everolimus 10 mg/day orally (n = 44) and matching placebo (n =
      35). The primary endpoint was progression-free survival (PFS). Adverse events
      were also examined. The median PFS was 15.47 months with everolimus [95%
      confidence interval (CI) 10.52-26.37], as compared to 4.29 months with placebo
      (95% CI 2.22-10.75), representing a 72% reduction in the risk of progression or
      death (hazard ratio 0.27; 95% CI 0.13-0.59; P < 0.001). Drug-associated adverse
      events (AEs) were mostly grade 1 or 2, observed in all 44 (100%) patients
      receiving everolimus and in 29 (83%) patients receiving placebo. The most common
      AEs (grade 1-4) associated with everolimus were rash (n = 38; 86%), stomatitis (n
      = 30; 68%), infections (n = 33; 75%), epistaxis (n = 32; 73%), pneumonitis (n =
      27; 61%) and anemia (n = 22; 50%). Everolimus when compared with placebo is
      effectively in improving PFS in Chinese patients with PNETs.

PMID- 25395379
TI  - Past, present, and future steps in child abuse and neglect issues: the Serbian
      journey.

PMID- 25395380
TI  - Long-term course of ADHD symptoms from childhood to early adulthood in a
      community sample.
AB  - Comparatively little information is available from population-based studies on
      subgroup trajectories of attention-deficit/hyperactivity disorder (ADHD) core
      symptoms of inattention and hyperactivity-impulsivity (particularly as defined by
      DSM-IV and ICD-10). Recent report of a subgroup with high and increasing
      inattention symptoms across development requires replication. To identify the
      different trajectory subgroups for inattention, hyperactivity-impulsivity and
      total symptoms of ADHD in children and adolescents aged 7-19 years. Eleven birth
      cohorts from 2,593 families with children and adolescents who had parent ratings
      for the outcome measures of inattention, hyperactivity-impulsivity or total
      symptoms were considered. Data were analysed using an accelerated longitudinal
      design and growth mixture modelling was applied to detect subgroups. For all
      three outcome measures, three trajectories with low (78.3-83.3 %), moderate (13.4
      18.8 %) and high (2.8-3.2 %) symptom levels were detected. Course within these
      subgroups was largely comparable across outcome domains. In general, a decrease
      in symptoms with age was observed in all severity subgroups, although the
      developmental course was stable for the high subgroups of inattention and total
      symptoms. About 3 % of children in a community-based sample follow a course with
      a high level of ADHD symptoms. In this high trajectory group, hyperactivity
      impulsivity symptoms decrease with age from 7 to 19 years, whilst inattention and
      total symptoms are stable. There was no evidence for an increase in symptoms
      across childhood/adolescence in any of the severity groups. 

PMID- 25395381
TI  - A randomised controlled trial of a web-based educational program in child mental
      health for schoolteachers.
AB  - Children affected by mental disorders are largely unrecognised and untreated
      across the world. Community resources, including the school system and teachers,
      are important elements in actions directed to promoting child mental health and
      preventing and treating mental disorders, especially in low- and middle-income
      countries. We developed a web-based program to educate primary school teachers on
      mental disorders in childhood and conducted a cluster-randomised controlled trial
      to test the effectiveness of the web-based program intervention in comparison
      with the same program based on text and video materials only and to a waiting
      list control group. All nine schools of a single city in the state of Sao Paulo,
      Brazil, were randomised to the three groups, and teachers completed the
      educational programs during 3 weeks. Data were analysed according to complete
      cases and intention-to-treat approaches. In terms of gains of knowledge about
      mental disorders, the web-based program intervention was superior to the
      intervention with text and video materials, and to the waiting-list control
      group. In terms of beliefs and attitudes about mental disorders, the web-based
      program intervention group presented less stigmatised concepts than the text and
      video group and more non-stigmatised concepts than the waiting-list group. No
      differences were detected in terms of teachers' attitudes. This study
      demonstrated initial data on the effectiveness of a web-based program in
      educating schoolteachers on child mental disorders. Future studies are necessary
      to replicate and extend the findings.

PMID- 25395382
TI  - Cognitive bias and unusual experiences in childhood.
AB  - Cognitive therapy is recommended for children with psychotic-like, or unusual,
      experiences associated with distress or impairment (UEDs; UK National Institute
      for Health and Care Excellence, 2013 [1]). Accurate models of the psychological
      underpinnings of childhood UEDs are required to effectively target therapies.
      Cognitive biases, such as the jumping to conclusions data-gathering bias (JTC),
      are implicated in the development and maintenance of psychosis in adults. In this
      study, we aimed to establish the suitability for children of a task developed to
      assess JTC in adults. Eighty-six participants (aged 5-14 years) were recruited
      from Child and Adolescent Mental Health Service (CAMHS) and community (school)
      settings, and completed the probabilistic reasoning ('Beads') task, alongside
      measures of intellectual functioning, general psychopathology, and UEDs. Self
      reported reasoning strategy was coded as 'probabilistic' or 'other'. Younger
      children (5-10 years) were more likely than older children (11-14 years) to JTC
      (OR = 2.7, 95 % CI = 1.1-6.5, p = 0.03); and to use non-probabilistic reasoning
      strategies (OR = 9.4, 95 % CI = 1.7-48.8, p = 0.008). Both UED presence (OR =
      5.1, 95 % CI = 1.2-21.9, p = 0.03) and lower IQ (OR = 0.9, 95 % CI = 0.9-1.0, p =
      0.02) were significantly and independently associated with JTC, irrespective of
      age and task comprehension. Findings replicate research in adults, indicating
      that the 'Beads' task can be reliably employed in children to assess cognitive
      biases. Psychological treatments for children with distressing unusual
      experiences might usefully incorporate reasoning interventions.

PMID- 25395383
TI  - Combined stimulant and antipsychotic treatment in adolescents with attention
      deficit/hyperactivity disorder: a cross-sectional observational structural MRI
      study.
AB  - Meta-analyses suggest normalizing effects of methylphenidate on structural fronto
      striatal abnormalities in patients with attention-deficit/hyperactivity disorder
      (ADHD). A subgroup of patients receives atypical antipsychotics concurrent with
      methylphenidate. Long-term safety and efficacy of combined treatment are unknown.
      The current study provides an initial investigation of structural brain
      correlates of combined methylphenidate and antipsychotic treatment in patients
      with ADHD. Structural magnetic resonance imaging was obtained in 31 patients who
      had received combined methylphenidate and antipsychotic treatment, 31 matched
      patients who had received methylphenidate but not antipsychotics, and 31 healthy
      controls (M age 16.7 years). We analyzed between-group effects in total cortical
      and subcortical volume, and in seven frontal cortical and eight subcortical
      limbic volumes of interest, each involved in dopaminergic neurotransmission.
      Patients in the combined treatment group, but not those in the methylphenidate
      only group, showed a reduction in total cortical volume compared to healthy
      controls (Cohen's d = 0.69, p < 0.004), which was apparent in most frontal
      volumes of interest. Further, the combined treatment group, but not the
      methylphenidate group, showed volume reduction in bilateral ventral diencephalon
      (Left Cohen's d = 0.48, p < 0.04; Right Cohen's d = 0.46, p < 0.05) and the left
      thalamus (Cohen's d = 0.47, p < 0.04). These findings may indicate antipsychotic
      treatment counteracting the normalizing effects of methylphenidate on brain
      structure. However, it cannot be ruled out that pre-existing clinical differences
      between both patient groups may have resulted in anatomical differences at the
      time of scanning. The absence of an untreated ADHD group hinders unequivocal
      interpretation and implications of our findings.

PMID- 25395384
TI  - Emergence agitation after orthognathic surgery: a randomised controlled
      comparison between sevoflurane and desflurane.
AB  - BACKGROUND: This study aimed to compare emergence agitation following sevoflurane
      and desflurane anaesthesia in adults undergoing orthognathic surgery. The
      hypothesis was that there might be a difference in the incidence of emergence
      agitation following sevoflurane and desflurane anaesthesia considering the
      difference in blood solubility and speed of recovery between the two. METHODS: In
      this prospective randomised double-blind study, 144 adults undergoing
      orthognathic surgery were randomly allocated to either sevoflurane or desflurane
      anaesthesia. The incidence of emergence agitation and possible causative factors
      were then compared between the groups. RESULTS: The incidence of emergence
      agitation was lower in the desflurane group than in the sevoflurane group (24%
      vs. 71%, P < 0.001). In addition, the time intervals between the discontinuation
      of anaesthetics and the first response, extubation, and discharge from post
      anaesthesia care unit were significantly shorter in the desflurane group (P =
      0.002, P < 0.001 and P = 0.003, respectively). The other variables were similar
      in the two groups. CONCLUSIONS: In adults undergoing orthognathic surgery,
      desflurane anaesthesia was associated with less emergence agitation than was
      sevoflurane anaesthesia.

PMID- 25395385
TI  - Mutation studies in ascidians: a review.
AB  - Historically, mutations have had a significant impact on the study of
      developmental processes and phenotypic evolution. Lesions in DNA are created by
      artificial methods or detected by natural genetic variation. Random mutations are
      then ascribed to genetic change by direct sequencing or positional cloning.
      Tunicate species of the ascidian genus Ciona represent nearly fully realized
      model systems in which gene function can be investigated in depth. Additionally,
      tunicates are valuable organisms for the study of naturally occurring mutations
      due to the capability to exploit genetic variation down to the molecular level.
      Here, we summarize the available information about how mutations are studied in
      ascidians with examples of insights that have resulted from these applications.
      We also describe notions and methodologies that might be useful for the
      implementation of easy and tight procedures for mutations studies in Ciona.

PMID- 25395386
TI  - Efficacy of a sun protection workbook for kidney transplant recipients: a
      randomized controlled trial of a culturally sensitive educational intervention.
AB  - A culturally sensitive educational intervention that encouraged sun protection
      behaviors among kidney transplant recipients (KTRs) was developed and the short
      term efficacy was evaluated. Non-Hispanic White, Hispanic/Latino and non-Hispanic
      Black patients, who received a transplant 2-24 months prior to the study, were
      randomized into two study groups: intervention versus standard of care.
      Electronic reminders tailored to the weather conditions were sent every 2 weeks
      by text message or email. Self-reported surveys and biologic measurements were
      obtained prior to the intervention and 6 weeks later. Among the 101 study
      participants, there was a statistically significant increase in knowledge,
      recognition of personal risk of developing skin cancer, willingness to change sun
      protection behavior and self-reported performance of sun protection in
      participants receiving the intervention in comparison with those receiving
      standard of care (p < 0.05). The pigment darkening of the sun-exposed forearm and
      sun damage of the forearm and sunburns/skin irritation from the sun were
      significantly less in participants receiving the intervention (p < 0.05).
      Providing sun protection education at the beginning of summer with reminders
      tailored to weather conditions helped KTRs adopt sun protection practices. This
      sun protection program for KTRs may be incorporated into the care provided by the
      nephrologist or transplant surgeon. 

PMID- 25395387
TI  - Factors responsible for long-term survival in metastatic breast cancer.
AB  - BACKGROUND: Although survival of patients with metastatic breast cancer (MBC) has
      been significantly prolonged over the past decade due to improvement of anti
      cancer therapeutics, only a few patients survive for more than 10 years. It has
      not been determined which patients can have long-term survival with treatment.
      METHODS: To determine prognostic factors responsible for long-term survival, we
      retrospectively compared clinicopathologic factors of patients with MBC who
      survived for 50 months or more after diagnosis with patients who did not. Of 70
      patients with MBC who received chemotherapy between November 2005 and September
      2011, 23 patients who survived for 50 months or more after diagnosis and 28
      patients who died within 50 months after diagnosis were assessed for their
      clinicopathologic factors and outcomes. RESULTS: The proportion of patients with
      hormone receptor-positive (HR+) tumors was significantly higher and the
      proportion of patients with triple negative tumors (TN) was lower in long-term
      survivors than in non-long-term survivors (HR+: 87% versus 28.6%, P=0.000037; TN:
      13.1% versus 53.6%, P=0.0028). Metastatic site, number of disease sites, prior
      chemotherapeutic regimens and human epidermal growth factor receptor-2 (HER2)
      status did not differ between the two groups. The proportion of patients who
      received metronomic regimens was significantly higher in long-term survivors than
      in non-long-term survivors (65.2% versus 35.7%, P=0.034) when the most effective
      regimen among regimens that were received in metastatic settings was compared
      between the two groups. Overall response rate was significantly higher (82.6%
      versus 17.9%, P<0.00001) and time to treatment failure after receiving the most
      effective regimen was longer in long-term survivors than in non-long-term
      survivors (26 versus 5 months, P=0.0001). The number of chemotherapeutic regimens
      for breast cancer and that for MBC did not differ between the two groups.
      CONCLUSIONS: Patients with luminal-type MBC who benefit at least once from
      chemotherapy including metronomic regimens, or patients who continued to receive
      the most effective regimen for more than two years can be expected to have long
      term survival after diagnosis of MBC, regardless of the number of
      chemotherapeutic regimens they had received.

PMID- 25395388
TI  - Current controversies in prenatal diagnosis 4: pre-conception expanded carrier
      screening should replace all current prenatal screening for specific single gene
      disorders.

PMID- 25395389
TI  - Exhaustive methylation analysis revealed uneven profiles of methylation at
      IGF2/ICR1/H19 11p15 loci in Russell Silver syndrome.
AB  - BACKGROUND: The structural organisation of the human IGF2/ICR1/H19 11p15 domain
      is very complex, and the mechanisms underlying its regulation are poorly
      understood. The Imprinted Center Region 1 (ICR1) contains seven binding sites for
      the zinc-finger protein CTCF (CBS: CTCF Binding Sites); three additional
      differentially methylated regions (DMR) are located at the H19 promoter (H19DMR)
      and two in the IGF2 gene (DMR0 and DMR2), respectively. Loss of imprinting at the
      IGF2/ICR1/H19 domain results in two growth disorders with opposite phenotypes:
      Beckwith-Wiedemann syndrome and Russell Silver syndrome (RSS). Despite the
      IGF2/ICR1/H19 locus being widely studied, the extent of hypomethylation across
      the domain remains not yet addressed in patients with RSS. METHODS: We assessed a
      detailed investigation of the methylation status of the 11p15 ICR1 CBS1-7,
      IGF2DMR0 and H19DMR (H19 promoter) in a population of controls (n=50) and RSS
      carrying (n=104) or not (n=65) carrying a hypomethylation at the 11p15 ICR1
      region. RESULTS: The methylation indexes (MI) were balanced at all regions in the
      control population and patients with RSS without any as yet identified molecular
      anomaly. Interestingly, patients with RSS with ICR1 hypomethylation showed uneven
      profiles of methylation among the CBSs and DMRs. Furthermore, normal MIs at CBS1
      and CBS7 were identified in 9% of patients. CONCLUSIONS: The hypomethylation does
      not spread equally throughout the IGF2/ICR1/H19 locus, and some loci could have
      normal MI, which may lead to underdiagnosis of patients with RSS with ICR1
      hypomethylation. The uneven pattern of methylation suggests that some CBSs may
      play different roles in the tridimensional chromosomal looping regulation of this
      locus.

PMID- 25395391
TI  - New insights into the effect of haemodiafiltration on mortality: the Romanian
      experience.
AB  - BACKGROUND: Haemodiafiltration (HDF), by successfully removing the larger solutes
      and protein-bound compounds, may offer a feasible approach to improve dialysis
      outcomes. Recently, three large, randomized, controlled trials have tested this
      hypothesis, but only one showed an improved survival associated with HDF
      treatment, when compared with haemodialysis (HD). METHODS: This is a
      retrospective analysis of the entire Romanian dialysed population from the
      European Clinical Database (EUCLID) Fresenius Medical Care Database. We conducted
      two types of analysis. First, we used an intention-to-treat approach including
      all patients who were in dialysis (either HDF or HD) at 1 March 2010--'prevalent
      cohort analysis'. We then considered only the incident patients who started
      dialysis (either HDF or HD) after 1 March 2010--'incident cohort analysis'. In
      both analyses, patients were followed until 31 April 2013. RESULTS: In the
      prevalent cohort, we included 1546 patients who were already performing dialysis
      at the first time point-1322 on HD and 224 on HDF. When compared with HD, HDF
      treatment was associated with reduced mortality in both univariate and
      multivariate survival analysis (HR = 0.67, 95% CI 0.46-0.96 and HR = 0.58, 95% CI
      0.36-0.93, respectively). In the incident cohort, 2447 patients started dialysis
      (2181 HD and 266 HDF) during the observation period. Patients in the HDF group
      maintained a reduced risk for all-cause mortality (HR = 0.20, 95% CI 0.11-0.38
      for the univariate and HR = 0.24, 95% CI 0.13-0.46 for the fully adjusted model).
      CONCLUSIONS: This study suggests that HDF treatment could reduce all-cause
      mortality in incident and prevalent patients even after correction for different
      confounders. Interestingly, an additional survival benefit could be observed in
      incident patients. However, as with any observational study, there could have
      been other unmeasured confounders that could have influenced our final results.

PMID- 25395390
TI  - Prevalence and correlates of gout in a large cohort of patients with chronic
      kidney disease: the German Chronic Kidney Disease (GCKD) study.
AB  - BACKGROUND: Reduced kidney function is a risk factor for hyperuricaemia and gout,
      but limited information on the burden of gout is available from studies of
      patients with chronic kidney disease (CKD). We therefore examined the prevalence
      and correlates of gout in the large prospective observational German Chronic
      Kidney Disease (GCKD) study. METHODS: Data from 5085 CKD patients aged 18-74
      years with an estimated glomerular filtration rate (eGFR) of 30-<60 mL/min/1.73
      m(2) or eGFR >=60 and overt proteinuria at recruitment and non-missing values for
      self-reported gout, medications and urate measurements from a central laboratory
      were evaluated. RESULTS: The overall prevalence of gout was 24.3%, and increased
      from 16.0% in those with eGFR >=60 mL/min/1.73 m(2) to 35.6% in those with eGFR
      <30. Of those with self-reported gout, 30.7% of individuals were not currently
      taking any gout medication and among gout patients on urate lowering therapy,
      47.2% still showed hyperuricaemia. Factors associated with gout were serum urate,
      lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip
      ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol
      intake and diuretics use. While lower eGFR categories showed significant
      associations with gout in multivariable-adjusted models (prevalence ratio 1.46
      for eGFR <30 compared with eGFR >=60, 95% confidence interval 1.21-1.77),
      associations between gout and higher urinary albumin-to-creatinine ratio in this
      CKD population were not significant. CONCLUSIONS: Self-reported gout is common
      among patients with CKD and lower GFR is strongly associated with gout.
      Pharmacological management of gout in patients with CKD is suboptimal.
      Prospective follow-up will show whether gout and hyperuricaemia increase the risk
      of CKD progression and cardiovascular events in the GCKD study.

PMID- 25395392
TI  - Effect of oral liposomal iron versus intravenous iron for treatment of iron
      deficiency anaemia in CKD patients: a randomized trial.
AB  - INTRODUCTION: Iron deficiency is a common cause of anaemia in non-dialysis
      chronic kidney disease (ND-CKD). Controversies exist about the optimal route of
      administration for iron therapy. Liposomal iron, a new generation oral iron with
      high gastrointestinal absorption and bioavailability and a low incidence of side
      effects, seems to be a promising new strategy of iron replacement. Therefore, we
      conducted a study to determine whether liposomal iron, compared with intravenous
      (IV) iron, improves anaemia in ND-CKD patients. METHODS: In this randomized, open
      label trial, 99 patients with CKD (stage 3-5, not on dialysis) and iron
      deficiency anaemia [haemoglobin (Hb) <=12 g/dL, ferritin <=100 ng/mL, transferrin
      saturation <=25%] were assigned (2:1) to receive oral liposomal iron (30 mg/day,
      Group OS) or a total dose of 1000 mg of IV iron gluconate (125 mg infused weekly)
      (Group IV) for 3 months. The patients were followed-up for the treatment period
      and 1 month after drug withdrawal. The primary end point was to evaluate the
      effects of the two treatments on Hb levels; the iron status, compliance and
      adverse effects were also evaluated. RESULTS: The short-term therapy with IV iron
      produced a more rapid Hb increase compared with liposomal iron, although the
      final increase in Hb was similar with either treatment; the difference between
      the groups was statistically significant at the first month and such difference
      disappeared at the end of treatment. After iron withdrawal, Hb concentrations
      remained stable in Group IV, while recovered to baseline in the OS group. The
      replenishment of iron stores was greater in the IV group. The incidence of
      adverse event was significantly lower in the oral group (P < 0.001), and the
      adherence was similar in the two groups. CONCLUSIONS: Our study shows that oral
      liposomal iron is a safe and efficacious alternative to IV iron gluconate to
      correct anaemia in ND-CKD patients, although its effects on repletion of iron
      stores and on stability of Hb after drug discontinuation are lower.

PMID- 25395393
TI  - Absence of the calcium-binding protein, S100A1, confers pulmonary hypertension in
      mice associated with endothelial dysfunction and apoptosis.
AB  - AIMS: S100A1, a 10-kDa, Ca(2+)-binding protein, is expressed in endothelial cells
      (ECs) and binds eNOS. Its absence is associated with impaired production of
      nitric oxide (NO) and mild systemic hypertension. As endothelial dysfunction
      contributes to clinical and experimental pulmonary hypertension (PH), we
      investigated the impact of deleting S100A1 in mice, on pulmonary haemodynamics,
      endothelial function, NO production, associated signalling pathways, and
      apoptosis. METHODS AND RESULTS: Compared with wild-type (WT), S100A1-knock-out
      mice (KO) exhibited increased right ventricular (RV) weight/body weight ratio and
      elevated RV pressure in the absence of altered left ventricular filling
      pressures, accompanied by increase in wall thickness of muscularized pulmonary
      arteries and a reduction in microvascular perfusion. In isolated lung
      preparations, KO revealed reduced basal NO, blunted dose-responsiveness to
      acetylcholine, and augmented basal and angiotensin (AII)-induced pulmonary
      vascular resistance (R0) compared with WT. Pre-treatment of KO lungs with S100A1
      attenuated the AII-induced increase in pulmonary arterial pressure and R0. S100A1
      induced phosphorylation of eNOS, Akt, and ERK1/2 is attenuated in pulmonary EC of
      KO compared with WT. Basal and TNF-alpha-induced EC apoptosis is greater in KO
      vs. WT, and cell survival is enhanced by S100A1 treatment. CONCLUSION: Our data
      demonstrate that the absence of S100A1 results in PH by disruption of its normal
      capacity to (i) enhance pulmonary EC function by induction of eNOS activity and
      NO levels via Akt/ERK1/2 pathways and (ii) promote EC survival. The ability of
      exogenously administered S100A1 to rescue this phenotype makes it an attractive
      therapeutic target in the treatment of PH.

PMID- 25395394
TI  - Mediation of smoking abstinence self-efficacy on the association of nicotine
      dependence with smoking cessation.
AB  - BACKGROUND: The nicotine dependence (ND) has negative and smoking abstinence self
      efficacy (SASE) has positive effects on successful smoking cessation, but scant
      data is now available for what is the mediating role of SASE on the relationship
      between ND and successful smoking cessation. The aim of this study was to assess
      the abovementioned mediation. METHODS: A case-control study was conducted with
      642 successful spontaneous quitters as the cases, and 700 failed spontaneous
      quitters as the controls. ND and SASE were evaluated by Fagerstrom Test for
      Nicotine Dependence (FTND) scale and SASE scale, respectively. Propensity score
      as covariate in the regression model was used to adjust for potential confounders
      of age, age of smoking initiation, occupation, educational level and marital
      status. Total effect was decomposed into direct and indirect (mediating) effect
      using logistic regression based on the KHB method proposed by Holm et al.
      RESULTS: After adjusting for the aforementioned potential confounders, the
      mediating effects among the total effect of ND on successful spontaneous smoking
      cessation were 32.90%, 12.14%, 35.64% and 83.03% for the total score of SASE and
      its three context-specific situation scores, i.e. positive/social situation,
      negative/affective situation and habit/addictive situation, respectively.
      CONCLUSIONS: This study indicates that SASE has a partial mediating effect on the
      association of ND with successful spontaneous smoking cessation. To boost the
      smokers' SASE could increase the probability of successful smoking cessation.

PMID- 25395395
TI  - Socioeconomic determinants of prescribed and non-prescribed medicine consumption
      in Austria.
AB  - BACKGROUND: Equitable access to health care is a goal subscribed to in many
      European economies. But while a growing body of literature studies socioeconomic
      inequalities in health service use, relatively little is still known about
      inequalities in medicine consumption. Against this background, this study
      investigates the (socioeconomic) determinants of medicine use in the Austrian
      context. METHODS: Multivariate logistic regressions were estimated based on the
      European Health Interview Survey, including representative information of the
      Austrian population above age 25 (n = 13 291) for 2006/2007. As dependent
      variables, we used prescribed and non-prescribed medicine consumption as well as
      prescribed polypharmacy. Socioeconomic status was operationalized by employment
      status, education and net equivalent income. Health indicators (self-assessed
      health, chronic conditions), demographic characteristics (age, sex) and
      outpatient visits were included as control variables. RESULTS: Socioeconomic
      status revealed opposing utilization patterns: while individuals with higher
      education and income were more likely to consume non-prescribed medicines, the
      less educated were more likely to take prescribed medicines. Lower socioeconomic
      groups also showed a higher likelihood for prescribed polypharmacy. For the
      consumption of both medicine types, the main socioeconomic determinant was high
      income. In an additional analysis, lower socioeconomic groups were found to more
      likely report prescription purposes as the main reason for consulting a
      practitioner. CONCLUSION: These results point to different behavioural responses
      to ill health, not least determined by institutional incentives in the Austrian
      health care system.

PMID- 25395396
TI  - Associations of work and health-related characteristics with intention to
      continue working after the age of 65 years.
AB  - This study examines the association of work and health-related characteristics
      with the intention to continue working after the age of 65 years. Data were from
      the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a
      nationally representative population survey, including 1854 employees aged 45-64
      years; 29.0% reported the intention to continue working after 65 years. Lower
      education, more adverse psychosocial working conditions and any physical disorder
      were negatively associated with this intention. Mental disorders were not
      associated. These findings highlight the importance of favourable working
      conditions and good physical health in relation to employees' intention to
      continue working after 65 years. 

PMID- 25395397
TI  - Cost-related barriers to use of health services and prescription medicines in
      Finland: a cross-sectional survey.
AB  - BACKGROUND: The objective was to examine cost-related barriers to using health
      services and prescription medicines in Finland. METHODS: A survey that examined
      adults' experiences of and opinions about the social security system was mailed
      to a random population-based sample of 5000 Finns aged 18-74 years. The survey
      assessed households' cost-related barriers to use of health services,
      prescription medicines and social assistance in the past year. The responses were
      adjusted for sociodemographic and health predictors by weighting and logistic
      regression. RESULTS: Responses were received from 1770 households. In total, 18%
      had experienced at least one cost-related barrier; 11% did not fill a
      prescription, 8% did not go to hospital and 13% went without another form of
      treatment. Of respondents diagnosed with a disabling illness or impairment, 32%
      reported at least one cost-related barrier. Households with below-average income
      reported barriers twice as often as above-average income households, after
      adjusting for age and health. Lower income [lowest tertile, odds ratio (OR) 5.0
      compared with highest tertile], fair/poor self-assessed health (fair/poor OR 7.1
      compared with very good/good), younger age (18-34 years OR 3.8 compared with 65
      74 years), lower education (primary OR 1.6 compared with tertiary) and female
      gender (OR 1.4) were significantly associated with more frequent cost-related
      barriers. Overall, 34% of households who encountered cost-related barriers had
      applied for and 17% had received social assistance. CONCLUSIONS: Cost-related
      barriers were common among respondents with low income and/or poor health. These
      barriers may thus have a role in creating inequities in access to health care in
      Finland.

PMID- 25395398
TI  - Comparison of patients' experiences in public and private primary care clinics in
      Malta.
AB  - Demographic changes, technological developments and rising expectations require
      the analysis of public-private primary care (PC) service provision to inform
      policy makers. We conducted a descriptive, cross-sectional study using the
      dataset of the Maltese arm of the QUALICOPC Project to compare the PC patients'
      experiences provided by public-funded and private (independent) general
      practitioners in Malta. Seven hundred patients from 70 clinics completed a self
      administered questionnaire. Direct logistic regression showed that patients
      visiting the private sector experienced better continuity of care with more
      difficulty in accessing out-of-hours care. Such findings help to improve
      (primary) healthcare service provision and resource allocation. 

PMID- 25395399
TI  - Gender-specific modifying effect on the educational disparities in the impact of
      smoking on health expectancy.
AB  - BACKGROUND: Smoking reduces life years in good health but it is unclear how
      education modifies the impact of smoking. We hypothesize that the vulnerability
      of the effect of smoking on health expectancy decreases with educational level in
      both genders and examine the contributions of mortality and health effects.
      METHODS: Life tables by educational level and smoking category were constructed
      from registers and survey data. For each educational level, difference in
      expected lifetime in self-rated good and poor health between 30-year-old never
      smokers and smokers were estimated and decomposed into contributions from
      mortality and health status. RESULTS: Difference in expected lifetime in good
      health between never smokers and smokers decreased with educational level for
      women but increased for men. Thus, the differences between never smokers and
      heavy smokers among 30-year-old women with a low, medium and high educational
      level were 12.9, 8.9 and 4.1 years, respectively. In contrast, the differences
      between male never smokers and heavy smokers with a low, medium and high
      educational level were 10.3, 11.4 and 14.3 years, respectively. Regardless of
      educational level, the mortality effect increased by exposure to smoking but the
      effect of health status increased by educational level for men and decreased for
      women. CONCLUSION: The social differential vulnerability to the effect of smoking
      differed between genders. Thus, whereas smoking had a substantial effect on
      health among women with a low educational level the pattern for men was opposite
      because the health gain for never smokers was greatest for men with a high
      education.

PMID- 25395400
TI  - Association between process indicators and in-hospital mortality among patients
      with chronic heart failure in China.
AB  - BACKGROUND: Quality indicators for Chinese patients with chronic heart failure
      (CHF) have been developed. However, little is known about the compliance with
      quality indicators and the association between process indicators and in-hospital
      mortality in China. METHODS: Data from 1862 CHF admissions between 1 January 2009
      and 31 October 2010 at 20 tertiary hospitals in Heilongjiang Province were
      analyzed. Hierarchical generalized linear models were used to examine the
      association between six process indicators and in-hospital mortality in eligible
      patients. RESULTS: The in-hospital mortality for the 1862 patients was 4.7%. The
      compliance with six process indicators were: evaluation of left ventricular
      function, 66.4%; angiotensin-converting enzyme inhibitor (ACEI)/angiotensin
      receptor blocker (ARB), 54.9%; diuretic, 86.2%; beta-blocker, 45.1%; aldosterone
      receptor antagonist, 64.0%; and warfarin, 17.1%. Rates of compliance at the
      hospital level varied from 0 to 100%. After the adjustment for confounding
      factors, evaluation of left ventricular function, ACEI/ARB and aldosterone
      receptor antagonist were significantly associated with in-hospital mortality
      ([OR, 0.55; 95% CI, 0.33-0.93; P = 0.027], [OR, 0.33; 95% CI, 0.12-0.94; P =
      0.040] and [OR, 0.35; 95% CI, 0.13-0.98; P = 0.046], respectively). CONCLUSIONS:
      There are considerable gaps between guidelines and clinical practice and
      variations across hospitals for the treatment of patients with CHF. Evaluation of
      left ventricular function, ACEI/ARB and aldosterone receptor antagonist will
      reduce the risk of in-hospital mortality. The association of other process
      indicators with clinical outcomes remain to be established.

PMID- 25395401
TI  - Concurrent validation of two key health literacy instruments in a South Eastern
      European population.
AB  - BACKGROUND: Public health practice has come to increasing recognition of health
      promotion and the central role of knowledge, attitude, beliefs and practices in
      achieving health promotion. Health literacy (HL) is an under-explored topic in
      South Eastern European countries. There are no HL reports from Albania to date.
      The aim of this study was to assess the concurrent validity of the European
      Health Literacy Survey Questionnaire (HLS-EU-Q) and the Test of Functional Health
      Literacy in Adults (TOFHLA) in a population-based sample of adults in Albania.
      METHODS: A cross-sectional study was conducted in 2013 in Tirana, Albania,
      including 239 individuals aged >= 18 years (61% women; 87% response). A
      structured interviewer-administered questionnaire was applied twice (test and
      retest procedure after 2 weeks) including HLS-EU-Q and TOFHLA instruments.
      RESULTS: The internal consistency was high for both instruments (Cronbach's alpha
      for the test procedure was 0.92 for TOFHLA and 0.98 for HLS-EU-Q). Both tools
      exhibited a high stability over time (Spearman's rho: 0.88 for TOFHLA and 0.87
      for HLS-EU). Mean values of both instruments were similar in men and women (mean
      score for TOFHLA: 76.0 vs. 76.5, P = 0.83; mean score for HLS-EU-Q: 32.2 vs.
      32.6, P = 0.63). For both instruments, higher HL scores were significantly
      associated with younger age, higher educational and economic level and lower body
      mass index. CONCLUSIONS: Our study provides valuable novel evidence on concurrent
      validation of two major HL instruments in a South Eastern European population
      based sample. Future studies should be conducted in order to confirm and expand
      our findings.

PMID- 25395402
TI  - Secular trends in BMI and the prevalence of obesity in young Polish males from
      1965 to 2010.
AB  - BACKGROUND: Obesity is a serious public health problem, the prevalence of which
      is increasing dramatically all over the world. The aim of this study was to
      examine trends in body mass index (BMI) and the proportion of overweight and
      obese individuals among 19-year-old Polish males reporting for mandatory military
      fitness exams from 1965 to 2010. METHODS: Height, weight and BMI [weight
      (kg)/height (m(2))] in five 10% nationwide random samples of 19-year-old
      conscripts examined in 1965, 1986, 1995, 2001 and 2010 were analysed. RESULTS:
      From 1965 to 2010, mean BMI in 19-year-old Polish males increased from 21.7 to
      22.9. The rate of change was not uniform, with a rapid increase in mean BMI from
      1995 to 2010. Beginning in 1965, the proportion of men with a BMI over 25 has
      been steadily increasing from one decade to the next, and was four times higher
      in 2010 than it was in 1965. The rate of increase per decade was twice as high
      from 2001 to 2010 than it was from 1995 to 2001. In 2010, only 70.8% of young men
      were of ideal weight. CONCLUSION: Increase in obesity can be attributed to the
      social and economic changes brought about by the transformation of the country
      from a communist to a free-market economy in 1989. The challenges of the obesity
      epidemic for public health services and its impact on morbidity and life
      expectancy are also discussed.

PMID- 25395403
TI  - Improvements in school meal quality in Sweden after the introduction of new
      legislation-a 2-year follow-up.
AB  - BACKGROUND: Sweden provides a free school lunch to every child in the compulsory
      (9-year) school system. It consists of a hot meal, a salad buffet, bread and a
      beverage. The Education Act states it must be free of charge (since 1997) and
      'nutritious' (since 2011). No standards/limits are specified but voluntary
      guidelines for serving of the school meal exist. We describe how school meal
      quality has changed since 2011. METHODS: A random sample of schools were
      contacted in spring 2011 and invited to use a novel web-based instrument to
      evaluate school meal quality. In spring 2013, the participating schools (N = 191)
      were encouraged to use it again and 97 did. The outcomes were measures of quality
      including food provision/choice, adherence to serving guidelines and, using
      validated food-based criteria, nutritional quality. RESULTS: No change was seen
      in the proportion offering alternative options daily, but a vegetarian option was
      significantly more widely available in 2013. Adherence to all but one of the
      studied serving guidelines improved, although this reached significance for only
      a small number. Adherence to two of the four nutrient criteria improved
      significantly. CONCLUSION: Two years after the introduction of new legislation,
      school meal quality in Sweden has improved modestly. The effect of the law itself
      is difficult to separate from other influences, including the effect of
      monitoring. Extended follow-up of schools will allow us to evaluate the longer
      term changes and effects on health, learning and equality in health.

PMID- 25395404
TI  - Semi-rational approach for converting a GH36 alpha-glycosidase into an alpha
      transglycosidase.
AB  - A large number of retaining glycosidases catalyze both hydrolysis and
      transglycosylation reactions. In order to use them as catalysts for
      oligosaccharide synthesis, the balance between these two competing reactions has
      to be shifted toward transglycosylation. We previously designed a semi-rational
      approach to convert the Thermus thermophilus beta-glycosidases into
      transglycosidases by mutating highly conserved residues located around the -1
      subsite. In an attempt to verify that this strategy could be a generic approach
      to turn glycosidases into transglycosidases, Geobacillus stearothermophilus alpha
      galactosidase (AgaB) was selected in order to obtain alpha-transgalactosidases.
      This is of particular interest as, to date, there are no efficient alpha
      galactosynthases, despite the considerable importance of alpha
      galactooligosaccharides. Thus, by site-directed mutagenesis on 14 AgaB residues,
      26 single mutants and 22 double mutants were created and screened, of which 11
      single mutants and 6 double mutants exhibited improved synthetic activity,
      producing 4-nitrophenyl alpha-d-galactopyranosyl-(1,6)-alpha-d-galactopyranoside
      in 26-57% yields against only 22% when native AgaB was used. It is interesting to
      note that the best variant was obtained by mutating a second-shell residue, with
      no direct interaction with the substrate or a catalytic amino acid. As this
      approach has proved to be efficient with both alpha- and beta-glycosidases, it is
      a promising route to convert retaining glycosidases into transglycosidases. 

PMID- 25395405
TI  - Golgi N-glycan branching N-acetylglucosaminyltransferases I, V and VI promote
      nutrient uptake and metabolism.
AB  - Nutrient transporters are critical gate-keepers of extracellular metabolite entry
      into the cell. As integral membrane proteins, most transporters are N
      glycosylated, and the N-glycans are remodeled in the Golgi apparatus. The Golgi
      branching enzymes N-acetylglucosaminyltransferases I, II, IV, V and avian VI
      (encoded by Mgat1, Mgat2, Mgat4a/b/c Mgat5 and Mgat6), each catalyze the addition
      of N-acetylglucosamine (GlcNAc) in N-glycans. Here, we asked whether N-glycan
      branching promotes nutrient transport and metabolism in immortal human HeLa
      carcinoma and non-malignant HEK293 embryonic kidney cells. Mgat6 is absent in
      mammals, but ectopic expression can be expected to add an additional beta1,4
      linked branch to N-glycans, and may provide evidence for functional redundancy of
      the N-glycan branches. Tetracycline (tet)-induced overexpression of Mgat1, Mgat5
      and Mgat6 resulted in increased enzyme activity and increased N-glycan branching
      concordant with the known specificities of these enzymes. Tet-induced Mgat1,
      Mgat5 and Mgat6 combined with stimulation of hexosamine biosynthesis pathway
      (HBP) to UDP-GlcNAc, increased cellular metabolite levels, lactate and oxidative
      metabolism in an additive manner. We then tested the hypothesis that N-glycan
      branching alone might promote nutrient uptake when glucose (Glc) and glutamine
      are limiting. In low glutamine and Glc medium, tet-induced Mgat5 alone increased
      amino acids uptake, intracellular levels of glycolytic and TCA intermediates, as
      well as HEK293 cell growth. More specifically, tet-induced Mgat5 and HBP elevated
      the import rate of glutamine, although transport of other metabolites may be
      regulated in parallel. Our results suggest that N-glycan branching cooperates
      with HBP to regulate metabolite import in a cell autonomous manner, and can
      enhance cell growth in low-nutrient environments. 

PMID- 25395407
TI  - Letter by Haft regarding article, "High prevalence of atrial fibrillation among
      patients with ischemic stroke".

PMID- 25395406
TI  - Affinities of human histo-blood group antigens for norovirus capsid protein
      complexes.
AB  - The binding profiles of many human noroviruses (huNoVs) for human histo-blood
      group antigens have been characterized. However, quantitative-binding data for
      these important virus-host interactions are lacking. Here, we report on the
      intrinsic (per binding site) affinities of HBGA oligosaccharides for the huNoV
      VA387 virus-like particles (VLPs) and the associated subviral P particles
      measured using electrospray ionization mass spectrometry. The affinities of 13
      HBGA oligosaccharides, containing A, B and H epitopes, with variable sizes
      (disaccharide to tetrasaccharide) and different precursor chain types (types 1,
      2, 3, 5 and 6), were measured for the P particle, while the affinities of the A
      and B trisaccharides and A and B type 6 tetrasaccharides for the VLP were
      determined. The intrinsic affinities of the HBGA oligosaccharides for the P
      particle range from 500 to 2300 M(-1), while those of the A and B trisaccharides
      and the A and B type 6 tetrasaccharides for the VLP range from 1000 to 4000 M(
      1). Comparison of these binding data with those measured previously for the
      corresponding P dimer reveals that the HBGA oligosaccharides tested exhibit
      similar intrinsic affinities for the P dimer and P particle. The intrinsic
      affinities for the VLP are consistently higher than those measured for the P
      particle, but within a factor of three. While the cause of the subtle differences
      in HBGA oligosaccharide affinities for the P dimer and P particle and those for
      the VLP remains unknown, the present data support the use of P dimers or P
      particles as surrogates to the VLP for huNoV-receptor-binding studies. 

PMID- 25395408
TI  - Implications of INTERACT2 and other clinical trials: blood pressure management in
      acute intracerebral hemorrhage.

PMID- 25395409
TI  - Ovarian hyperstimulation syndrome and arterial stroke.

PMID- 25395411
TI  - Clinical, radiological, and flow-related risk factors for growth of untreated,
      unruptured intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Unruptured intracranial aneurysms are frequently followed
      to monitor aneurysm growth. We studied the yield of follow-up imaging and
      analyzed risk factors for aneurysm growth. METHODS: We included patients with
      untreated, unruptured intracranial aneurysms and >=6 months of follow-up imaging
      from 2 large prospectively collected databases. We assessed the proportion of
      patients with aneurysm growth and performed univariable and multivariable Cox
      regression analyses to calculate hazard ratios with corresponding 95% confidence
      intervals (CI) for clinical and radiological risk factors for aneurysm growth. We
      repeated these analyses for the subset of small (<7 mm) aneurysms. RESULTS: Fifty
      seven (12%) of 468 aneurysms in 363 patients grew during a median follow-up of
      2.1 years (total follow-up, 1372 patient-years). In multivariable analysis,
      hazard ratios for aneurysm growth were as follows: 1.1 (95% CI, 1.0-1.2) per each
      additional mm of initial aneurysm size; 2.7 (95% CI, 1.2-6.4) for dome > neck
      ratio; 2.1 (95% CI, 0.9-4.9) for location in the posterior circulation; and 2.0
      (95% CI, 0.8-4.8) for multilobarity. In the subset of aneurysms <7 mm, 37 of 403
      (9%) enlarged. In multivariable analysis, hazard ratios for aneurysm growth were
      1.1 (95% CI, 0.8-1.5) per each additional mm of initial aneurysm size, 2.2 (95%
      CI, 1.0-4.8) for smoking, 2.9 (95% CI, 1.0-8.5) for multilobarity, 2.4 (95% CI,
      1.0-5.8) for dome/neck ratio, and 2.0 (95% CI, 0.6-7.0) for location in the
      posterior circulation. CONCLUSIONS: Initial aneurysm size, dome/neck ratio, and
      multilobarity are risk factors for aneurysm growth. Cessation of smoking is
      pivotal because smoking is a modifiable risk factor for growth of small
      aneurysms.

PMID- 25395410
TI  - Understanding the functions of endogenous and exogenous tissue-type plasminogen
      activator during stroke.

PMID- 25395412
TI  - Feasibility platform for stroke studies: an online tool to improve eligibility
      criteria for clinical trials.
AB  - BACKGROUND AND PURPOSE: Eligibility criteria are a key factor for the feasibility
      and validity of clinical trials. We aimed to develop an online tool to assess the
      potential effect of inclusion and exclusion criteria on the proportion of
      patients eligible for an acute stroke trial. METHODS: We identified relevant
      inclusion and exclusion criteria of acute stroke trials. Based on these criteria
      and using a cohort of 1537 consecutive patients with acute ischemic stroke from 3
      stroke centers, we developed a web portal feasibility platform for stroke studies
      (FePASS) to estimate proportions of eligible patients for acute stroke trials. We
      applied the FePASS resource to calculate the proportion of patients eligible for
      4 recent stroke studies. RESULTS: Sixty-one eligibility criteria were derived
      from 30 trials on acute ischemic stroke. FePASS, publicly available at
      http://fepass.uni-muenster.de, displays the proportion of patients in percent to
      assess the effect of varying values of relevant eligibility criteria, for
      example, age, symptom onset time, National Institutes of Health Stroke Scale, and
      prestroke modified Rankin Scale, on this proportion. The proportion of eligible
      patients for 4 recent stroke studies ranged from 2.1% to 11.3%. Slight variations
      of the inclusion criteria could substantially increase the proportion of eligible
      patients. CONCLUSIONS: FePASS is an open access online resource to assess the
      effect of inclusion and exclusion criteria on the proportion of eligible patients
      for a stroke trial. FePASS can help to design stroke studies, optimize
      eligibility criteria, and to estimate the potential recruitment rate.

PMID- 25395413
TI  - Misery perfusion, blood pressure control, and 5-year stroke risk in symptomatic
      major cerebral artery disease.
AB  - BACKGROUND AND PURPOSE: The benefit of strict blood pressure (BP) control in high
      risk patients with symptomatic major cerebral artery disease and misery perfusion
      (MP) is controversial. Our purposes were (1) to determine whether MP is a
      predictor of a 5-year risk of subsequent stroke and (2) to investigate the
      relationships among BP during follow-up, MP, and the stroke risk. METHODS: We
      studied 130 nondisabled patients with symptomatic major cerebral artery disease.
      Baseline hemodynamic measurements were obtained from (15)O-gas positron emission
      tomography, and patients received medical treatment and they were followed for 5
      years or until stroke recurrence or death. RESULTS: During 5 years, strokes
      occurred in 6 of 16 patients with MP and in 15 of 114 without MP (log-rank test;
      P<0.01). There were 4 (25%) ipsilateral ischemic strokes in patients with MP and
      4 in those without MP (P<0.001). The risk of ipsilateral ischemic stroke declined
      markedly after 2 years, and there was only 1 ipsilateral ischemic stroke in a
      patient without MP. Normal systolic BP (<130 mm Hg) was associated with an
      increased risk of ipsilateral ischemic strokes in patients with impaired
      perfusion (including MP), whereas systolic BP outside the 130 to 149 mm Hg range
      was associated with an increased risk of all strokes in patients without MP.
      CONCLUSION: Patients with MP showed a high-5-year stroke recurrence, but a large
      part of the 5-year stroke risk disappeared after 2 years. Aggressive BP control
      may be hazardous in patients with impaired perfusion, including MP.

PMID- 25395414
TI  - White matter microstructural damage in small vessel disease is associated with
      Montreal cognitive assessment but not with mini mental state examination
      performances: vascular mild cognitive impairment Tuscany study.
AB  - BACKGROUND AND PURPOSE: Montreal Cognitive Assessment (MoCA) has been proposed as
      a screening tool in vascular cognitive impairment. Diffusion tensor imaging is
      sensitive to white matter microstructural damage. We investigated if diffusion
      tensor imaging-derived indices are more strongly associated with performances on
      MoCA or on the widely used mini mental state examination in patients with mild
      cognitive impairment and small vessel disease. METHODS: Mild cognitive impairment
      patients with moderate/severe degrees of white matter hyperintensities on MRI
      were enrolled. Lacunar infarcts, cortical atrophy, medial temporal lobe atrophy
      and median values of mean diffusivity and fractional anisotropy of the cerebral
      white matter were studied and correlated with cognitive tests performances.
      RESULTS: Seventy-six patients (mean age 75.1+/-6.8 years, mean years of education
      8.0+/-4.3) were assessed. In univariate analyses, a significant association of
      both MoCA and mini mental state examination scores with age, education, cortical
      atrophy, and medial temporal lobe atrophy was found, whereas mean diffusivity and
      fractional anisotropy were associated with MoCA. In partial correlation analyses,
      adjusting for all demographic and neuroimaging variables, both mean diffusivity
      and fractional anisotropy were associated only with MoCA (mean diffusivity: r= 
      0.275, P=0.023; fractional anisotropy: r=0.246, P=0.043). CONCLUSIONS: In
      patients with mild cognitive impairment and small vessel disease, diffusion
      tensor imaging-measured white matter microstructural damage is more related to
      MoCA than mini mental state examination performances. MoCA is suited for the
      cognitive screening of patients with small vessel disease.

PMID- 25395415
TI  - Functional outcome after common poststroke complications occurring in the first
      90 days.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to explore the associations of
      common medical complications with functional outcome at 90 days post stroke.
      METHODS: Patients with unselected acute stroke were included and observed for 16
      predefined complications during the first week. Fifty percent (244 patients) were
      allocated to follow-up of 13 complications until 90 days and then assessed with
      the modified Rankin Scale 90. Common complications were defined as complications
      with frequencies of >=5%. Ordinal logistic regression (worsened outcome), as well
      as binary logistic regression for severe dependency and death (modified Rankin
      Scale score>3) was performed. RESULTS: Seven of the 13 complications occurred at
      a frequency >=5%. Recurrent stroke and chest infection were found to have an odds
      ratio for worsened outcome of 7.45 (95% confidence interval, 2.83-20.96;
      P<0.0001) and 3.28 (95% confidence interval, 1.16-9.29; P=0.025), respectively.
      Infections other than chest infections and urinary tract infections had an odds
      ratio for worsened outcome of 1.59 (95% confidence interval, 1.12-2.24; P=0.009)
      and falls an odds ratio of 1.43 (95% confidence interval, 1.06 to 1.93; P=0.021).
      Myocardial infarction, urinary tract infections, and pain were not associated
      with a worsened outcome in terms of modified Rankin Scale 90. CONCLUSIONS:
      Recurrent stroke and chest infections were strongly associated with a worsened
      outcome. Other infections and falls were associated with less worsening. For
      myocardial infarction, urinary tract infections, and pain no association with
      functional outcome was found. Active strategies for prevention and early
      treatment of the first 2 complications seem advisable; patient monitoring as part
      of comprehensive stroke unit care should ensure timely identification and
      treatment of all complications.

PMID- 25395416
TI  - Response to letter regarding article, "High prevalence of atrial fibrillation
      among patients with ischemic stroke".

PMID- 25395417
TI  - Brain-derived neurotrophic factor administration mediated oligodendrocyte
      differentiation and myelin formation in subcortical ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Translational research is beginning to reveal the
      importance of trophic factors as a therapy for cellular brain repair. The purpose
      of this study was to analyze whether brain-derived neurotrophic factor (BDNF)
      administration could mediate oligodendrogenesis and remyelination after white
      matter injury in subcortical stroke. METHODS: Ischemia was induced in rats by
      injection of endothelin-1. At 24 hours, 0.4 MUg/kg of BDNF or saline was
      intravenously administered to the treatment and control groups, respectively.
      Functional evaluation, MRI, and fiber tract integrity on tractography images were
      analyzed. Proliferation (KI-67) and white matter repair markers (A2B5, 2',3'
      cyclic-nucleotide 3'-phosphodiesterase [CNPase], adenomatous polyposis coli
      [APC], platelet-derived growth factor receptor alpha [PDGFR-alpha],
      oligodendrocyte marker O4 [O4], oligodendrocyte transcription factor [Olig-2],
      and myelin basic protein [MBP]) were analyzed at 7 and 28 days. RESULTS: The BDNF
      treated animals showed less functional deficit at 28 days after treatment than
      the controls (P<0.05). Although T2-MRI did not show differences in lesion size at
      7 and 28 days between groups, diffusion tensor imaging tractography analysis
      revealed significantly better tract connectivity at 28 days in the BDNF group
      than in the controls (P<0.05). Increased proliferation of oligodendrocyte
      progenitors was observed in treated animals at 7 days (P<0.05). Finally, the
      levels of white matter repair markers (A2B5, CNPase, and O4 at 7 days; Olig-2 and
      MBP at 28 days) were higher in the BDNF group than in the controls (P<0.05).
      CONCLUSIONS: BDNF administration exerted better functional outcome,
      oligodendrogenesis, remyelination, and fiber connectivity than controls in rats
      subjected to subcortical damage in ischemic stroke.

PMID- 25395418
TI  - Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic
      leukemia.
AB  - Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative
      neoplasm of childhood associated with a poor prognosis. Recently, massively
      parallel sequencing has identified recurrent mutations in the SKI domain of
      SETBP1 in a variety of myeloid disorders. These lesions were detected in nearly
      10% of patients with JMML and have been characterized as secondary events. We
      hypothesized that rare subclones with SETBP1 mutations are present at diagnosis
      in a large portion of patients who relapse, but are below the limits of detection
      for conventional deep sequencing platforms. Using droplet digital polymerase
      chain reaction, we identified SETBP1 mutations in 17/56 (30%) of patients who
      were treated in the Children's Oncology Group sponsored clinical trial, AAML0122.
      Five-year event-free survival in patients with SETBP1 mutations was 18% +/- 9%
      compared with 51% +/- 8% for those without mutations (P = .006). 

PMID- 25395419
TI  - ATL response to arsenic/interferon therapy is triggered by SUMO/PML/RNF4
      dependent Tax degradation.
AB  - The human T-cell lymphotropic virus type I (HTLV-1) Tax transactivator initiates
      transformation in adult T-cell leukemia/lymphoma (ATL), a highly aggressive
      chemotherapy-resistant malignancy. The arsenic/interferon combination, which
      triggers degradation of the Tax oncoprotein, selectively induces apoptosis of ATL
      cell lines and has significant clinical activity in Tax-driven murine ATL or
      human patients. However, the role of Tax loss in ATL response is disputed, and
      the molecular mechanisms driving degradation remain elusive. Here we demonstrate
      that ATL-derived or HTLV-1-transformed cells are dependent on continuous Tax
      expression, suggesting that Tax degradation underlies clinical responses to the
      arsenic/interferon combination. The latter enforces promyelocytic leukemia
      protein (PML) nuclear body (NB) formation and partner protein recruitment. In
      arsenic/interferon-treated HTLV-1 transformed or ATL cells, Tax is recruited onto
      NBs and undergoes PML-dependent hyper-sumoylation by small ubiquitin-like
      modifier (SUMO)2/3 but not SUMO1, ubiquitination by RNF4, and proteasome
      dependent degradation. Thus, the arsenic/interferon combination clears ATL
      through degradation of its Tax driver, and this regimen could have broader
      therapeutic value by promoting degradation of other pathogenic sumoylated
      proteins. 

PMID- 25395421
TI  - Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease
      sustainer and disease accelerator.
AB  - Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms
      (MPNs). We examined the individual and cooperative effects of these mutations on
      MPN development. Recipients of JAK2V617F cells developed primary myelofibrosis
      like features; the addition of loss of TET2 worsened this JAK2V617F-induced
      disease, causing prolonged leukocytosis, splenomegaly, extramedullary
      hematopoiesis, and modestly shorter survival. Double-mutant (JAK2V617F plus loss
      of TET2) myeloid cells were more likely to be in a proliferative state than
      JAK2V617F single-mutant myeloid cells. In a serial competitive transplantation
      assay, JAK2V617F cells resulted in decreased chimerism in the second recipients,
      which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and
      loss of TET2 developed and maintained MPNs in the second recipients by
      compensating for impaired hematopoietic stem cell (HSC) functioning. In-vitro
      sequential colony formation assays also supported the observation that JAK2V617F
      did not maintain HSC functioning over the long-term, but concurrent loss of TET2
      mutation restored it. Transcriptional profiling revealed that loss of TET2
      affected the expression of many HSC signature genes. We conclude that loss of
      TET2 has two different roles in MPNs: disease accelerator and disease initiator
      and sustainer in combination with JAK2V617F. 

PMID- 25395422
TI  - Boost and loss of immune responses against tumor-associated antigens in the
      course of pregnancy as a model for allogeneic immunotherapy.
AB  - Donor-derived immunity against tumor-associated antigens (TAAs) may exert
      selective antileukemic activity reprieving the allogeneic recipient from graft
      versus-host disease. As TAAs are highly expressed in placental tissues we
      hypothesized that pregnancy could drive respective immunity in healthy
      individuals. Thus, we investigated the frequency and level of immune responses
      against clinically relevant TAAs in 114 blood donors and 44 women during their
      first pregnancy. Quantitative reverse-transcription polymerase chain reaction was
      employed to detect low levels of interferon-gamma after primary peptide
      stimulation of CD8(+) T lymphocytes. In blood donors, primary immune responses of
      low and/or high avidity were found against WT1 (15%), MUC1 (14%), PRAME (7%), and
      HER2/neu (5%) and exerted killing functions against leukemic cells. Men had
      higher responses than women, likely due to gonadal cancer-testis-antigen
      expression. Interestingly, a history of prior delivery was not associated with
      increased responses, whereas the strongest responses during pregnancy were found
      in early trimesters to disappear after delivery. This boost and loss of TAA
      specific immunity suggests that virtually every donor harbors the potential to
      mount antileukemic immune responses in a recipient. However, in the absence of
      the driving target and a permissive environment, they are short-lived and thus
      require supplemental strategies such as vaccination or immunomodulation to
      facilitate their persistence. 

PMID- 25395420
TI  - RNA interference screening identifies lenalidomide sensitizers in multiple
      myeloma, including RSK2.
AB  - To identify molecular targets that modify sensitivity to lenalidomide, we
      measured proliferation in multiple myeloma (MM) cells transfected with 27 968
      small interfering RNAs in the presence of increasing concentrations of drug and
      identified 63 genes that enhance activity of lenalidomide upon silencing.
      Ribosomal protein S6 kinase (RPS6KA3 or RSK2) was the most potent sensitizer.
      Other notable gene targets included 5 RAB family members, 3 potassium channel
      proteins, and 2 peroxisome family members. Single genes of interest included I
      kappa-B kinase-alpha (CHUK), and a phosphorylation dependent transcription factor
      (CREB1), which associate with RSK2 to regulate several signaling pathways. RSK2
      knockdown induced cytotoxicity across a panel of MM cell lines and consistently
      increased sensitivity to lenalidomide. Accordingly, 3 small molecular inhibitors
      of RSK2 demonstrated synergy with lenalidomide cytotoxicity in MM cells even in
      the presence of stromal contact. Both RSK2 knockdown and small molecule
      inhibition downregulate interferon regulatory factor 4 and MYC, and provides an
      explanation for the synergy between lenalidomide and RSK2 inhibition.
      Interestingly, RSK2 inhibition also sensitized MM cells to bortezomib, melphalan,
      and dexamethasone, but did not downregulate Ikaros or influence lenalidomide
      mediated downregulation of tumor necrosis factor-alpha or increase lenalidomide
      induced IL-2 upregulation. In summary, inhibition of RSK2 may prove a broadly
      useful adjunct to MM therapy.

PMID- 25395423
TI  - Myosin-II repression favors pre/proplatelets but shear activation generates
      platelets and fails in macrothrombocytopenia.
AB  - Megakaryocyte ploidy and the generation of pre/proplatelets are both increased in
      culture by pharmacologic inhibition of myosin-II, but nonmuscle myosin-IIA (MIIA)
      mutations paradoxically cause MYH9-related diseases (MYH9-RD) that adversely
      affect platelets. In marrow, megakaryocytes extend projections into the
      microcirculation, where shear facilitates fragmentation to large
      pre/proplatelets, suggesting that fluid stresses and myosin-II activity somehow
      couple in platelet biogenesis. Here, in bulk shear, plateletlike particles
      generated from megakaryocytes are maximized at a shear stress typical of that in
      the microcirculation and after treatment with a myosin-II inhibitor. MIIA
      activity in static cells is naturally repressed through phosphorylation at Serine
      1943, but shear decreases phosphorylation, consistent with MIIA activation and
      localization to platelet cortex. Micropipette aspiration of cells shows myosin-II
      accumulates at stressed sites, but its inhibition prevents such mechanoactivation
      and facilitates generation of CD41(+) fragments similar in size to
      pre/proplatelets. MYH9-RD mutants phenocopy inhibition, revealing a dominant
      negative effect. MIIA is diffuse in the large platelets of a MYH9-RD patient with
      macrothrombocytopenia and is also diffuse in normal pre/proplatelets treated with
      inhibitor that blocks in vitro division to small platelets. The findings explain
      the large platelets in MYH9-RD and the near-normal thrombocrit of patients.
      Myosin-II regulation thus controls platelet size and number. 

PMID- 25395424
TI  - von Willebrand factor is a cofactor in complement regulation.
AB  - Several complement proteins interact with hemostatic factors. We discovered that
      von Willebrand factor (VWF) acts as a cofactor for factor I-mediated cleavage of
      complement C3b, thereby shutting down complement activation. The complement
      regulatory function of VWF multimers depends on their size. Smaller VWF multimers
      enhance cleavage of C3b but large and ultra-large VWF (ULVWF) multimers have no
      effect on C3b cleavage and permit default complement activation. We conclude that
      normal plasma VWF multimers prevent complement activation and steer the
      complement pathway toward generation of inactivated C3b (iC3b). ULVWF multimers,
      as are present in patients with thrombotic microangiopathy, lack an inhibitory
      effect on complement and permit complement activation. 

PMID- 25395425
TI  - Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk
      limited-stage aggressive B-cell lymphoma: SWOG S0313.
AB  - In the S0313 trial, we evaluated the impact of adding ibritumomab tiuxetan
      consolidation to 3 cycles of standard cyclophosphamide, doxorubicin, vincristine,
      and prednisone (CHOP) chemotherapy plus involved field radiotherapy (IFRT) in
      patients with limited-stage aggressive B-cell non-Hodgkin lymphoma (LD-NHL).
      Patients with at least 1 stage-modified adverse risk factor (nonbulky stage II,
      age >60 years, elevated lactate dehydrogenase, or World Health Organization
      performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3
      weeks later by 40 to 50 Gy of IFRT. An ibritumomab tiuxetan regimen was initiated
      3 to 6 weeks following IFRT. Forty-six patients were registered and eligible,
      with median follow-up of 7.3 years. The progression-free survival estimate is 89%
      at 2 years, 82% at 5 years, and 75% at 7 years. The overall survival estimate is
      91% at 2 years, 87% at 5 years, and 82% at 7 years. Grade 4 adverse events
      occurring more than once included neutropenia (8), leukopenia (5), and
      lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of
      treatment-related myeloid neoplasms were noted. In conclusion, patients with high
      risk LD-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab
      tiuxetan consolidation had outcomes that compare favorably to our historical
      experience. The clinical trial was registered at www.clinicaltrials.gov as
      #NCT00070018. 

PMID- 25395426
TI  - An RCOR1 loss-associated gene expression signature identifies a prognostically
      significant DLBCL subgroup.
AB  - Effective treatment of diffuse large B-cell lymphoma (DLBCL) is plagued by
      heterogeneous responses to standard therapy, and molecular mechanisms underlying
      unfavorable outcomes in lymphoma patients remain elusive. Here, we profiled 148
      genomes with 91 matching transcriptomes in a DLBCL cohort treated with rituximab
      plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) to
      uncover molecular subgroups linked to treatment failure. Systematic integration
      of high-resolution genotyping arrays and RNA sequencing data revealed novel
      deletions in RCOR1 to be associated with unfavorable progression-free survival (P
      = .001). Integration of expression data from the clinical samples with data from
      RCOR1 knockdowns in the lymphoma cell lines KM-H2 and Raji yielded an RCOR1 loss
      associated gene signature comprising 233 genes. This signature identified a
      subgroup of patients with unfavorable overall survival (P = .023). The prognostic
      significance of the 233-gene signature for overall survival was reproduced in an
      independent cohort comprising 195 R-CHOP-treated patients (P = .039).
      Additionally, we discovered that within the International Prognostic Index low
      risk group, the gene signature provides additional prognostic value that was
      independent of the cell-of-origin phenotype. We present a novel and reproducible
      molecular subgroup of DLBCL that impacts risk-stratification of R-CHOP-treated
      DLBCL patients and reveals a possible new avenue for therapeutic intervention
      strategies. 

PMID- 25395427
TI  - Upregulation of FcgammaRIIb on monocytes is necessary to promote the superagonist
      activity of TGN1412.
AB  - The anti-CD28 superagonist antibody TGN1412 caused life-threatening cytokine
      release syndrome (CRS) in healthy volunteers, which had not been predicted by
      preclinical testing. T cells in fresh peripheral blood mononuclear cells (PBMCs)
      do not respond to soluble TGN1412 but do respond following high-density (HD)
      preculture. We show for the first time that this response is dependent on
      crystallizable fragment gamma receptor IIb (FcgammaRIIb) expression on monocytes.
      This was unexpected because, unlike B cells, circulating monocytes express little
      or no FcgammaRIIb. However, FcgammaRIIb expression is logarithmically increased
      on monocytes during HD preculture, and this upregulation is necessary and
      sufficient to explain TGN1412 potency after HD preculture. B-cell FcgammaRIIb
      expression is unchanged by HD preculture, but B cells can support TGN1412
      mediated T-cell proliferation when added at a frequency higher than that in
      PBMCs. Although low-density (LD) precultured PBMCs do not respond to TGN1412, T
      cells from LD preculture are fully responsive when cocultured with FcgammaRIIb
      expressing monocytes from HD preculture, which shows that they are fully able to
      respond to TGN1412-mediated activation. Our novel findings demonstrate that cross
      linking by FcgammaRIIb is critical for the superagonist activity of TGN1412 after
      HD preculture, and this may contribute to CRS in humans because of the close
      association of FcgammaRIIb-bearing cells with T cells in lymphoid tissues.

PMID- 25395428
TI  - Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule
      suppresses MLL-rearranged leukemia.
AB  - Enhancer of zeste homolog 2 (EZH2) and related EZH1 control gene expression and
      promote tumorigenesis via methylating histone H3 at lysine 27 (H3K27). These
      methyltransferases are ideal therapeutic targets due to their frequent
      hyperactive mutations and overexpression found in cancer, including hematopoietic
      malignancies. Here, we characterized a set of small molecules that allow
      pharmacologic manipulation of EZH2 and EZH1, which include UNC1999, a selective
      inhibitor of both enzymes, and UNC2400, an inactive analog compound useful for
      assessment of off-target effect. UNC1999 suppresses global H3K27
      trimethylation/dimethylation (H3K27me3/2) and inhibits growth of mixed lineage
      leukemia (MLL)-rearranged leukemia cells. UNC1999-induced transcriptome
      alterations overlap those following knockdown of embryonic ectoderm development,
      a common cofactor of EZH2 and EZH1, demonstrating UNC1999's on-target inhibition.
      Mechanistically, UNC1999 preferentially affects distal regulatory elements such
      as enhancers, leading to derepression of polycomb targets including Cdkn2a. Gene
      derepression correlates with a decrease in H3K27me3 and concurrent gain in H3K27
      acetylation. UNC2400 does not induce such effects. Oral administration of UNC1999
      prolongs survival of a well-defined murine leukemia model bearing MLL-AF9.
      Collectively, our study provides the detailed profiling for a set of chemicals to
      manipulate EZH2 and EZH1 and establishes specific enzymatic inhibition of
      polycomb repressive complex 2 (PRC2)-EZH2 and PRC2-EZH1 by small-molecule
      compounds as a novel therapeutics for MLL-rearranged leukemia. 

PMID- 25395430
TI  - Coronary steal or large collateral? Three cases of graft failure in sequential
      and composite grafts.
AB  - Coronary bypass grafting using conduits with multiple distal anastomoses
      continues to demand scrutiny. While on one hand these techniques allow the
      surgeon to avoid or minimise aortic manipulation, the unique flow and pressure
      characteristics lead to complex forms of graft failure if the anatomy of the
      target vascular bed is not carefully taken into consideration. We report three
      cases of graft failure in patients with coronary bypass grafting performed using
      multiple distal anastomoses, and percutaneous revascularisation in one patient. 

PMID- 25395429
TI  - Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity
      in patients with relapsed multiple myeloma.
AB  - Dysregulation of cyclin-dependent kinases is a hallmark of myeloma, and
      specifically, cdk5 inhibition can enhance the activity of proteasome inhibitors
      in vitro. Dinaciclib is a novel potent small molecule inhibitor of cyclin
      dependent kinases (CDK)1, CDK2, CDK5, and CDK9. Patients with relapsed multiple
      myeloma and <=5 prior lines of therapy, with measurable disease, were enrolled.
      Dinaciclib was administered on day 1 of a 21-day cycle at doses of 30 to 50
      mg/m(2). Overall, 27 evaluable patients were accrued; the median number of prior
      therapies was 4. The dose level of 50 mg/m(2) was determined to be the maximally
      tolerated dose. The overall confirmed partial response rate (PR) was 3 of 27
      (11%), including 1 patient at the 30 mg/m(2) dose (1 very good PR [VGPR]) and 2
      patients at the 40 mg/m(2) dose (1 VGPR and 1 PR). In addition, 2 patients at the
      50 mg/mg(2) dose achieved a minimal response (clinical benefit rate, 19%).
      Leukopenia, thrombocytopenia, gastrointestinal symptoms, alopecia, and fatigue
      were the most common adverse events. The current study demonstrates single agent
      activity of dinaciclib in relapsed myeloma, with 2 patients achieving a deep
      response (VGPR) and 10 patients obtaining some degree of M protein stabilization
      or decrease. This trial was registered at www.clinicaltrials.gov as #NCT01096342.

PMID- 25395431
TI  - We don't prescribe statins to lower cholesterol: we prescribe statins to reduce
      vascular risk.

PMID- 25395433
TI  - Patients will have digital access to GP records by 2015, says NHS England.

PMID- 25395432
TI  - Contrasting Cholesterol Management Guidelines for Adults with CKD.
AB  - The Kidney Disease Improving Global Outcomes Lipid Work Group recommends statins
      for adults >=50 years old with CKD. The American College of Cardiology/American
      Heart Association endorses statins for adults with atherosclerotic cardiovascular
      disease, adults with LDL cholesterol>=190 mg/dl, and adults 40-79 years old with
      LDL cholesterol=70-189 mg/dl and diabetes or a 10-year predicted risk for
      atherosclerotic cardiovascular disease >=7.5% estimated using the Pooled Cohort
      risk equations. Using data from the Reasons for Geographic and Racial Differences
      in Stroke Study, we calculated the agreement for statin treatment between these
      two guidelines for adults 50-79 years old with CKD (eGFR<60 ml/min per 1.73 m(2)
      or albuminuria>=30 mg/g) not on dialysis. We assessed the validity of the Pooled
      Cohort risk equations in individuals with CKD. Study participants were enrolled
      between 2003 and 2007, and we report incident cardiovascular disease events
      (stroke and coronary heart disease) through December of 2010. Among 4726
      participants with CKD, 2366 (50%) were taking statins, and 1984 (42%) were
      recommended statins by the American College of Cardiology/American Heart
      Association guideline but not taking them. Overall, 376 (8%) participants did not
      meet the American College of Cardiology/American Heart Association criteria for
      initiating statin treatment. Cardiovascular disease incidence was low (3.0/1000
      person-years; 95% confidence interval, 0.1 to 5.9) among these participants. The
      Pooled Cohort risk equations were well calibrated (Hosmer-Lemeshow chi
      squared=2.7, P=0.45) with moderately good discrimination (C index, 0.71; 95%
      confidence interval, 0.65 to 0.77). In conclusion, these guidelines show high
      concordance for statin treatment for adults with CKD. 

PMID- 25395434
TI  - Three novel lineages of 'Candidatus Liberibacter africanus' associated with
      native rutaceous hosts of Trioza erytreae in South Africa.
AB  - Greening disease of citrus in South Africa is associated with 'Candidatus
      Liberibacter africanus' (Laf), a phloem-limited bacterium vectored by the sap
      sucking insect Trioza erytreae (Triozidae). Despite the implementation of control
      strategies, this disease remains problematic, suggesting the existence of
      reservoir hosts to Laf. The current study aimed to identify such hosts. Samples
      from 234 trees of Clausena anisata, 289 trees of Vepris lanceolata and 231 trees
      of Zanthoxylum capense were collected throughout the natural distribution of
      these trees in South Africa. Total DNA was extracted from samples and tested for
      the presence of liberibacters by a generic Liberibacter TaqMan real-time PCR
      assay. Liberibacters present in positive samples were characterized by amplifying
      and sequencing rplJ, omp and 16S rRNA gene regions. The identity of tree host
      species from which liberibacter sequences were obtained was verified by
      sequencing host rbcL genes. Of the trees tested, 33 specimens of Clausena, 17
      specimens of Vepris and 10 specimens of Zanthoxylum tested positive for
      liberibacter. None of the samples contained typical citrus-infecting Laf
      sequences. Phylogenetic analysis of 16S rRNA gene sequences indicated that the
      liberibacters obtained from Vepris and Clausena had 16S rRNA gene sequences
      identical to that of 'Candidatus Liberibacter africanus subsp. capensis' (LafC),
      whereas those from Zanthoxylum species grouped separately. Phylogenetic analysis
      of the rplJ and omp gene regions revealed unique clusters for liberibacters
      associated with each tree species. We propose the following names for these novel
      liberibacters: 'Candidatus Liberibacter africanus subsp. clausenae' (LafCl),
      'Candidatus Liberibacter africanus subsp. vepridis' (LafV) and 'Candidatus
      Liberibacter africanus subsp. zanthoxyli' (LafZ). This study did not find any
      natural hosts of Laf associated with greening of citrus. While native citrus
      relatives were shown to be infected with Laf-related liberibacters, nucleotide
      sequence data suggest that these are not alternative sources of Laf to citrus
      orchards, per se. 

PMID- 25395435
TI  - A quarter of women who undergo breast conserving surgery need further surgery,
      research shows.

PMID- 25395436
TI  - The first 25 years of History of Psychiatry.

PMID- 25395437
TI  - Some reflections on madness and culture in the post-war world.
AB  - This article examines the treatment of madness as a theme in drama, opera and
      films, concentrating its attention for the most part on the period between World
      War II and the 1980s. These were the years in which psychoanalysis dominated
      psychiatry in the USA, and so Freud's influence in the broader culture forms the
      central though not the sole focus of the analysis. 

PMID- 25395438
TI  - Nostalgia: a conceptual history.
AB  - The term nostalgia was first proposed in 1688 by Johannes Hofer as equivalent to
      the German term Heimweh. It referred to a state of moral pain associated with the
      forced separation from family and social environment. Consecutive clinical
      descriptions from the seventeenth century up to the present day have been
      subjected to the aetiopathogenic and clinical paradigms of each period. Golden
      age descriptions of nostalgia that are of particular interest were derived from
      the observation of conscript soldiers in Napoleonic campaigns by authors such as
      Gerbois and Larrey. In 1909 Jaspers devoted his doctoral thesis to this topic
      (Nostalgia und Verbrechen). From a cultural history point of view, it could be
      considered today as an example of 'transient illness'. The nosological relay has
      taken place through clinical pictures such as the pathology associated with
      exile, forced displacements and psychosis of captivity.

PMID- 25395439
TI  - 'An atmosphere of cure': Frederick Mott, shell shock and the Maudsley.
AB  - Although recognized as a medical scientist, the work of Frederick Mott as a
      physician, educator and clinical policymaker has been overshadowed. As a late
      entrant to the asylum system, Mott questioned established practices of treating
      mentally-ill patients and campaigned for reform. During World War I, entrusted
      with the management of the Maudsley neurological section, he sought to raise
      clinical standards and experimented with a range of therapies designed to treat
      the most severe or intractable forms of shell shock. While Mott believed that
      psychiatric disorder was underwritten by inherited characteristics, he did not
      dismiss the impact of the environment. The diversity of his interests has led to
      an understatement of his contribution as a physician, not only to the design and
      founding of the Maudsley Hospital but also to the therapeutic regime practised
      there during the interwar period.

PMID- 25395440
TI  - [Languages and the history of psychiatry].

PMID- 25395441
TI  - The birth of schizophrenia or a very modern Bleuler: a close reading of Eugen
      Bleuler's 'Die Prognose der Dementia praecox' and a re-consideration of his
      contribution to psychiatry.
AB  - After Eugen Bleuler introduced 'schizophrenia' in 1908, the term was hotly
      debated but eventually led to the abandonment of Kraepelin's previous term
      'dementia praecox'. Bleuler's contribution has subsequently been interpreted in
      two main ways. One tradition holds that Bleuler merely renamed 'dementia praecox'
      while conceptually continuing the Kraepelinian tradition. The other, focusing on
      Bleuler's characterization of 'dementia praecox' in terms of specific
      psychological alterations, accredits him with a genuine re-conceptualization.
      Based on a close reading of 'Die Prognose der Dementia praecox', the paper in
      which Bleuler first mentioned 'schizophrenia', we suggest a further
      interpretation of Bleuler's contribution and argue that the main motive for his
      re-conceptualization is to be found in his rejection of Kraepelinian nosology.

PMID- 25395442
TI  - Madness as disability.
AB  - How does society imagine mental illness? Does this shift radically over time and
      with different social attitudes as well as scientific discoveries about the
      origins and meanings of mental illness? What happens when we begin to think about
      mental illness as madness, as a malleable concept constantly shifting its
      meaning? We thus look at the meanings associated with 'general paralysis of the
      insane' in the nineteenth century and autism today in regard to disability. In
      this case study we examine the claims by scholars such as the anthropologist
      Emily Martin and the psychiatrist Kay Jamison as to the relationship between
      mental illness, disability and creativity. Today, the health sciences have become
      concerned with mental illness as a form of disability. How does this change the
      meaning of madness for practitioners and patients? 

PMID- 25395443
TI  - Psychiatric 'diseases' in history.
AB  - A history of psychiatry cannot step back from the question of psychiatric
      diseases, but the field has in general viewed psychiatric entities as
      manifestations of the human state rather than medical diseases. There is little
      acknowledgement that a true disease is likely to rise and fall in incidence. In
      outlining the North Wales History of Mental Illness project, this paper seeks to
      provide some evidence that psychiatric diseases do rise and fall in incidence,
      along with evidence as to how such ideas are received by other historians of
      psychiatry and by biological psychiatrists. 

PMID- 25395444
TI  - Subjectivity in clinical practice: on the origins of psychiatric semiology in
      early French alienism.
AB  - The aim of this article is to contribute to the analysis of the origins of
      psychiatric semiology, which by emphasizing subjectivity in clinical practice,
      gave birth to psychopathology as the scientific and intellectual enterprise of
      alienism. In other words, beyond simple anatomical and clinical observation,
      there was an effort to 'listen to' and 'read' the patient's delirium. In essence,
      the basic thesis which this short paper seeks to defend is that, despite a
      growing anatomical and clinical mind-set and a clear interest in physically
      locating mental illness within the body, during the Romantic period, psychiatry
      was able to construct a semiology largely based on the experience of the ego, on
      the inner world of the individual. This makes it possible to establish, from a
      clinical perspective, that the birth of alienism - of psychiatry - must be
      situated within the framework of a modernity in which the culture of subjectivity
      was one of its most characteristic features. 

PMID- 25395445
TI  - White men and weak masculinity: men in the public asylums in Victoria, Australia,
      and New Zealand, 1860s-1900s.
AB  - This article reveals a set of formulations of masculine identity through the
      fragments of extant casebook evidence from nineteenth-century psychiatric
      institutions in Victoria, Australia, and Auckland, New Zealand. It shows that
      some patterns in the identification of masculinity and insanity emerge, also
      highlighting the relevance of individual stories and 'cases' to fully understand
      how masculine identities were fashioned through medical institutional language. 

PMID- 25395446
TI  - The distinction between 'Passion' and 'Emotion'. Vincenzo Chiarugi: a case study.
AB  - The distinction between 'passion' and 'emotion' has been largely overlooked in
      the history of psychiatry and the psychopathology of affectivity. A version of
      the distinction that has gone completely unnoticed is the one proposed by
      Florentine physician Vincenzo Chiarugi (1759-1820). The purpose of the present
      discussion is to introduce this Italian version of the distinction and to inquire
      into its origins. 

PMID- 25395447
TI  - The ten most important changes in psychiatry since World War II.
AB  - Writing the recent history of a subject is notoriously difficult because of the
      lack of perspective and impartiality. One way to gain insight and understanding
      into the recent past of a discipline of knowledge is to consult directly the
      living practitioners who actually experienced first-hand the major changing
      circumstances in the discipline during the period under study. This article seeks
      to explore the most significant changes occurring in Western, and especially
      American, psychiatry from the end of World War II up to the present by
      interrogating a representative selection of psychiatrists and psychologists about
      the subject. Over a three-year period, the author surveyed approximately 200
      mental health experts on their perceptions of change in the world of psychiatric
      theory and practice during this enormously eventful 70-year period. After
      presenting the survey results, the article then attempts to analyse the answers
      that the author did (and did not) obtain from his poll-taking subjects. 

PMID- 25395448
TI  - 'Introduction' to 'Episodic Psychoses', by Erik Stromgren (1940).
AB  - This anniversary Classic Text, the 'Introduction' from Stromgren's 'Episodic
      Psychoses', provides a comprehensive, concise and erudite exposition of the
      history, nosography and nosology of these conditions. Stromgren traces the origin
      of this term and concepts back to Magnan's degeneration psychoses and associated
      'syndromes episodiques'. Especially inspired by 'the psychogenic psychosis'
      (1916), the seminal work by his mentor, August Wimmer, he convincingly shows that
      the episodic psychoses constitute an intermediate link between the degeneration
      psychoses, now an obsolete term, and the psychogenic psychoses, reactive
      psychoses and brief reactive psychoses, which in their own right have been a bone
      of contention in international psychiatry for many decades and an obstacle in
      achieving consensus in international psychiatric classification. 

PMID- 25395450
TI  - Essential nutrient supplementation prevents heritable metabolic disease in
      multigenerational intrauterine growth-restricted rats.
AB  - Intrauterine growth restriction (IUGR) confers heritable alterations in DNA
      methylation, rendering risk of adult metabolic syndrome (MetS). Because CpG
      methylation is coupled to intake of essential nutrients along the one-carbon
      pathway, we reasoned that essential nutrient supplementation (ENS) may abrogate
      IUGR-conferred multigenerational MetS. Pregnant Sprague-Dawley rats underwent
      bilateral uterine artery ligation causing IUGR in F1. Among the F2 generation,
      IUGR lineage rats were underweight at birth (6.7 vs. 8.0 g, P < 0.0001) and obese
      by adulthood (p160: 613 vs. 510 g; P < 0.0001). Dual energy X-ray absorptiometry
      studies revealed increased central fat mass (Delta+40 g), accompanied by
      dyslipidemic (>30% elevated, P < 0.05) serum triglycerides (139 mg/dl), very-LDLs
      (27.8 mg/dl), and fatty acids (632 uM). Hyperglycemic-euglycemic clamp studies
      and glucose tolerance testing revealed insulin resistance. Conversely, IUGR
      lineage ENS-fed rats did not manifest MetS, with significantly lower body weight
      (p160: 410 g), >5-fold less central fat mass, normal hepatic glucose efflux, and
      >70% reduced circulating triglycerides and very-LDLs compared with IUGR control
      fed F2 offspring (P < 0.01). Moreover, increased methylation of the IGF-1 P2
      transcriptional start site among IUGR lineage F2 offspring was reversed in ENS (P
      < 0.04). This is an initial demonstration that supplementation along the one
      carbon pathway abrogates adult morbidity and associated epigenomic modifications
      of IGF-1 in a rodent model of multigenerational MetS.

PMID- 25395451
TI  - 20S proteasome activation promotes life span extension and resistance to
      proteotoxicity in Caenorhabditis elegans.
AB  - Protein homeostasis (proteostasis) is one of the nodal points that need to be
      preserved to retain physiologic cellular/organismal balance. The ubiquitin
      proteasome system (UPS) is responsible for the removal of both normal and damaged
      proteins, with the proteasome being the downstream effector. The proteasome is
      the major cellular protease with progressive impairment of function during aging
      and senescence. Despite the documented age-retarding properties of proteasome
      activation in various cellular models, simultaneous enhancement of the 20S core
      proteasome content, assembly, and function have never been reported in any
      multicellular organism. Consequently, the possible effects of the core proteasome
      modulation on organismal life span are elusive. In this study, we have achieved
      activation of the 20S proteasome at organismal level. We demonstrate enhancement
      of proteasome levels, assembly, and activity in the nematode Caenorhabditis
      elegans, resulting in life span extension and increased resistance to stress. We
      also provide evidence that the observed life span extension is dependent on the
      transcriptional activity of Dauer formation abnormal/Forkhead box class O (DAF
      16/FOXO), skinhead-1 (SKN-1), and heat shock factor-1 (HSF-1) factors through
      regulation of downstream longevity genes. We further show that the reported
      beneficial effects are not ubiquitous but they are dependent on the genetic
      context. Finally, we provide evidence that proteasome core activation might be a
      potential strategy to minimize protein homeostasis deficiencies underlying
      aggregation-related diseases, such as Alzheimer's disease (AD) or Huntington's
      disease (HD). In summary, this is the first report demonstrating that 20S core
      proteasome up-regulation in terms of both content and activity is feasible in a
      multicellular eukaryotic organism and that in turn this modulation promotes
      extension of organismal health span and life span.

PMID- 25395452
TI  - Combination therapy of mesenchymal stem cells and serelaxin effectively
      attenuates renal fibrosis in obstructive nephropathy.
AB  - Chronic kidney disease (CKD) results from the development of fibrosis, ultimately
      leading to end-stage renal disease (ESRD). Although human bone marrow-derived
      mesenchymal stem cells (MSCs) can accelerate renal repair following acute injury,
      the establishment of fibrosis during CKD may affect their potential to influence
      regeneration capacity. Here we tested the novel combination of MSCs with the
      antifibrotic serelaxin to repair and protect the kidney 7 d post-unilateral
      ureteral obstruction (UUO), when fibrosis is established. Male C57BL6 mice were
      sham-operated or UUO-inured (n = 4-6) and received vehicle, MSCs (1 * 10(6)),
      serelaxin (0.5 mg/kg per d), or the combination of both. In vivo tracing studies
      with luciferin/enhanced green fluorescent protein (eGFP)-tagged MSCs showed
      specific localization in the obstructed kidney where they remained for 36 h.
      Combination therapy conferred significant protection from UUO-induced fibrosis,
      as indicated by hydroxyproline analysis (P < 0.001 vs. vehicle, P < 0.05 vs. MSC
      or serelaxin alone). This was accompanied by preserved structural architecture,
      decreased tubular epithelial injury (P < 0.01 vs. MSCs alone), macrophage
      infiltration, and myofibroblast localization in the kidney (both P < 0.01 vs.
      vehicle). Combination therapy also stimulated matrix metalloproteinase (MMP)-2
      activity over either treatment alone (P < 0.05 vs. either treatment alone). These
      results suggest that the presence of an antifibrotic in conjunction with MSCs
      ameliorates established kidney fibrosis and augments tissue repair to a greater
      extent than either treatment alone.

PMID- 25395453
TI  - Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy
      induces regression and significantly improves survival in a preclinical model of
      advanced stage epithelial ovarian cancer.
AB  - Most women are diagnosed with epithelial ovarian cancer (EOC) at advanced stage,
      where therapies have limited effectiveness and the long-term survival rate is
      low. We evaluated the effects of combined antiangiogenic and chemotherapy
      treatments on advanced stage EOC. Treatment of EOC cells with a recombinant
      version of the thrombospondin-1 type I repeats (3TSR) induced more apoptotic cell
      death (36.5 +/- 9.6%) in vitro compared to untreated controls (4.1 +/- 1.4). In
      vivo, tumors were induced in an orthotopic, syngeneic mouse model of advanced
      stage EOC. Mice were treated with 3TSR (4 mg/kg per day) alone or in combination
      with chemotherapy drugs delivered with maximum tolerated dose or metronomic
      scheduling. Pretreatment with 3TSR induced tumor regression, normalized tumor
      vasculature, and improved uptake of chemotherapy drugs. Combination 3TSR and
      metronomic chemotherapy induced the greatest tumor regression (6.2-fold reduction
      in size compared to PBS-treated controls) and highest survival when treatment was
      initiated at advanced stage. 3TSR binding to its receptor, CD36 (cluster of
      differentiation 36), increased binding of CD36 and SHP-1, which significantly
      inhibited phosphorylation of the VEGF receptor. In this study, we describe a
      novel treatment approach and mechanism of action with 3TSR and chemotherapy that
      induces regression of advanced stage EOC and significantly improves survival.
      Russell, S., Duquette, M., Liu, J., Drapkin, R., Lawler, J., Petrik, J. Combined
      therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces
      regression and significantly improves survival in a preclinical model of advanced
      stage epithelial ovarian cancer. 

PMID- 25395455
TI  - Transgenic analysis of a SoxB gene reveals neural progenitor cells in the
      cnidarian Nematostella vectensis.
AB  - Bilaterian neurogenesis is characterized by the generation of diverse neural cell
      types from dedicated neural stem/progenitor cells (NPCs). However, the
      evolutionary origin of NPCs is unclear, as neurogenesis in representatives of the
      bilaterian sister group, the Cnidaria, occurs via interstitial stem cells that
      also possess broader, non-neural, developmental potential. We address this
      question by analysing neurogenesis in an anthozoan cnidarian, Nematostella
      vectensis. Using a transgenic reporter line, we show that NvSoxB(2) - an
      orthologue of bilaterian SoxB genes that have conserved roles in neurogenesis -
      is expressed in a cell population that gives rise to sensory neurons, ganglion
      neurons and nematocytes: the three primary neural cell types of cnidarians. EdU
      labelling together with in situ hybridization, and within the NvSoxB(2)::mOrange
      transgenic line, demonstrates that cells express NvSoxB(2) before mitosis and
      identifies asymmetric behaviours of sibling cells within NvSoxB(2)(+) lineages.
      Morpholino-mediated gene knockdown of NvSoxB(2) blocks the formation of all three
      neural cell types, thereby identifying NvSoxB(2) as an essential positive
      regulator of nervous system development. Our results demonstrate that diverse
      neural cell types derive from an NvSoxB(2)-expressing population of mitotic cells
      in Nematostella and that SoxB genes are ancient components of a neurogenic
      program. To our knowledge this is the first description of a lineage-restricted,
      multipotent cell population outside the Bilateria and we propose that
      neurogenesis via dedicated, SoxB-expressing NPCs predates the split between
      cnidarians and bilaterians. 

PMID- 25395454
TI  - REVOLUTA and WRKY53 connect early and late leaf development in Arabidopsis.
AB  - As sessile organisms, plants have to continuously adjust growth and development
      to ever-changing environmental conditions. At the end of the growing season,
      annual plants induce leaf senescence to reallocate nutrients and energy-rich
      substances from the leaves to the maturing seeds. Thus, leaf senescence is a
      means with which to increase reproductive success and is therefore tightly
      coupled to the developmental age of the plant. However, senescence can also be
      induced in response to sub-optimal growth conditions as an exit strategy, which
      is accompanied by severely reduced yield. Here, we show that class III
      homeodomain leucine zipper (HD-ZIPIII) transcription factors, which are known to
      be involved in basic pattern formation, have an additional role in controlling
      the onset of leaf senescence in Arabidopsis. Several potential direct downstream
      genes of the HD-ZIPIII protein REVOLUTA (REV) have known roles in environment
      controlled physiological processes. We report that REV acts as a redox-sensitive
      transcription factor, and directly and positively regulates the expression of
      WRKY53, a master regulator of age-induced leaf senescence. HD-ZIPIII proteins are
      required for the full induction of WRKY53 in response to oxidative stress, and
      mutations in HD-ZIPIII genes strongly delay the onset of senescence. Thus, a
      crosstalk between early and late stages of leaf development appears to contribute
      to reproductive success. 

PMID- 25395456
TI  - Tracking developmentally regulated post-synthetic processing of homogalacturonan
      and chitin using reciprocal oligosaccharide probes.
AB  - Polysaccharides are major components of extracellular matrices and are often
      extensively modified post-synthetically to suit local requirements and
      developmental programmes. However, our current understanding of the
      spatiotemporal dynamics and functional significance of these modifications is
      limited by a lack of suitable molecular tools. Here, we report the development of
      a novel non-immunological approach for producing highly selective reciprocal
      oligosaccharide-based probes for chitosan (the product of chitin deacetylation)
      and for demethylesterified homogalacturonan. Specific reciprocal binding is
      mediated by the unique stereochemical arrangement of oppositely charged amino and
      carboxy groups. Conjugation of oligosaccharides to fluorophores or gold
      nanoparticles enables direct and rapid imaging of homogalacturonan and chitosan
      with unprecedented precision in diverse plant, fungal and animal systems. We
      demonstrated their potential for providing new biological insights by using them
      to study homogalacturonan processing during Arabidopsis thaliana root cap
      development and by analyzing sites of chitosan deposition in fungal cell walls
      and arthropod exoskeletons. 

PMID- 25395459
TI  - Less than half of people undergoing leg amputation get good care, inquiry warns.

PMID- 25395457
TI  - Epithelial beta1 integrin is required for lung branching morphogenesis and
      alveolarization.
AB  - Integrin-dependent interactions between cells and extracellular matrix regulate
      lung development; however, specific roles for beta1-containing integrins in
      individual cell types, including epithelial cells, remain incompletely
      understood. In this study, the functional importance of beta1 integrin in lung
      epithelium during mouse lung development was investigated by deleting the
      integrin from E10.5 onwards using surfactant protein C promoter-driven Cre. These
      mutant mice appeared normal at birth but failed to gain weight appropriately and
      died by 4 months of age with severe hypoxemia. Defects in airway branching
      morphogenesis in association with impaired epithelial cell adhesion and
      migration, as well as alveolarization defects and persistent macrophage-mediated
      inflammation were identified. Using an inducible system to delete beta1 integrin
      after completion of airway branching, we showed that alveolarization defects,
      characterized by disrupted secondary septation, abnormal alveolar epithelial cell
      differentiation, excessive collagen I and elastin deposition, and
      hypercellularity of the mesenchyme occurred independently of airway branching
      defects. By depleting macrophages using liposomal clodronate, we found that
      alveolarization defects were secondary to persistent alveolar inflammation. beta1
      integrin-deficient alveolar epithelial cells produced excessive monocyte
      chemoattractant protein 1 and reactive oxygen species, suggesting a direct role
      for beta1 integrin in regulating alveolar homeostasis. Taken together, these
      studies define distinct functions of epithelial beta1 integrin during both early
      and late lung development that affect airway branching morphogenesis, epithelial
      cell differentiation, alveolar septation and regulation of alveolar homeostasis. 

PMID- 25395458
TI  - Wnt/beta-catenin signaling integrates patterning and metabolism of the insect
      growth zone.
AB  - Wnt/beta-catenin and hedgehog (Hh) signaling are essential for transmitting
      signals across cell membranes in animal embryos. Early patterning of the
      principal insect model, Drosophila melanogaster, occurs in the syncytial
      blastoderm, where diffusion of transcription factors obviates the need for
      signaling pathways. However, in the cellularized growth zone of typical short
      germ insect embryos, signaling pathways are predicted to play a more fundamental
      role. Indeed, the Wnt/beta-catenin pathway is required for posterior elongation
      in most arthropods, although which target genes are activated in this context
      remains elusive. Here, we use the short germ beetle Tribolium castaneum to
      investigate two Wnt and Hh signaling centers located in the head anlagen and in
      the growth zone of early embryos. We find that Wnt/beta-catenin signaling acts
      upstream of Hh in the growth zone, whereas the opposite interaction occurs in the
      head. We determine the target gene sets of the Wnt/beta-catenin and Hh pathways
      and find that the growth zone signaling center activates a much greater number of
      genes and that the Wnt and Hh target gene sets are essentially non-overlapping.
      The Wnt pathway activates key genes of all three germ layers, including pair-rule
      genes, and Tc-caudal and Tc-twist. Furthermore, the Wnt pathway is required for
      hindgut development and we identify Tc-senseless as a novel hindgut patterning
      gene required in the early growth zone. At the same time, Wnt acts on growth zone
      metabolism and cell division, thereby integrating growth with patterning.
      Posterior Hh signaling activates several genes potentially involved in a
      proteinase cascade of unknown function. 

PMID- 25395460
TI  - The brain microenvironment: friend or foe for metastatic tumor cells?

PMID- 25395461
TI  - Druggable targets in pediatric neurocutaneous melanocytosis: Molecular and drug
      sensitivity studies in xenograft and ex vivo tumor cell culture to identify
      agents for therapy.
AB  - BACKGROUND: Neurocutaneous melanocytosis (NCM) is a rare congenital disorder that
      presents with pigmented cell lesions of the brain or leptomeninges in children
      with large or multiple congenital melanocytic nevi. Although the exact
      pathological processes involved are currently unclear, NCM appears to arise from
      an abnormal development of melanoblasts or melanocyte precursors. Currently, it
      has an extremely poor prognosis due to rapid disease progression and lack of
      effective treatment modalities. METHODS: In this study, we report on an
      experimental approach to examining NCM cells by establishing subcutaneous tumors
      in nude mice, which can be further expanded for conducting molecular and drug
      sensitivity experiments. RESULTS: Analysis of the NRAS gene-coding sequences of
      an established NCM cell line (YP-MEL) and NCM patient cells revealed
      heterogeneity in NRAS Q61K that activated mutation and possibly consequential
      differential sensitivity to MEK inhibition. Gene expression studies were
      performed to compare the molecular profiles of NCM cells with normal skin
      fibroblasts. In vitro cytotoxicity screens of libraries of targeted small
      molecule inhibitors revealed prospective agents for further evaluation.
      CONCLUSIONS: Our studies provide an experimental platform for the generation of
      NCM cells for preclinical studies and the production of molecular and in vitro
      data with which to identify druggable targets for the treatment.

PMID- 25395462
TI  - Subsequent neoplasms in survivors of childhood central nervous system tumors:
      risk after modern multimodal therapy.
AB  - BACKGROUND: Multimodal therapy has improved survival for some childhood CNS
      tumors. However, whether risk for subsequent neoplasms (SNs) also increases is
      unknown. We report the cumulative incidence of, and risk factors for, SNs after a
      childhood primary CNS tumor and determine whether treatment that combines
      radiation therapy (RT) with chemotherapy increases risk for SNs. METHODS:
      Analyses included 2779 patients with a primary CNS tumor treated at St Jude
      Children's Research Hospital between 1985 and 2012. Cumulative incidence and
      standardized incidence ratios (SIRs) were estimated for SNs confirmed by
      pathology report. Cumulative incidence among the 237 five-year medulloblastoma
      survivors treated with multimodal therapy (RT + chemotherapy) was compared with a
      historical cohort of 139 five-year survivors treated with RT but no chemotherapy
      in the Childhood Cancer Survivor Study. RESULTS: Eighty-one survivors had 97 SNs.
      The cumulative incidence of first SN was 3.0% (95% CI: 2.3%-3.9%) at 10 years,
      and 6.0% (95% CI: 4.6%-7.7%) at 20 years from diagnosis. Risks were highest for
      subsequent glioma, all grades (SIR = 57.2; 95% CI: 36.2-85.8) and acute myeloid
      leukemia (SIR = 31.8; 95% CI: 10.2-74.1). Compared with RT alone, RT +
      chemotherapy did not increase risk for SNs (hazard ratio: 0.64; 95% CI: 0.38
      1.06). Among five-year survivors of medulloblastoma treated with multimodal
      therapy, cumulative incidence of SN was 12.0% (95% CI: 6.4%-19.5%) at 20 years,
      no different than survivors treated with RT alone (11.3%, P = .44). CONCLUSION:
      The cumulative incidence of SNs continues to increase with time from treatment
      with no obvious plateau, but the risk does not appear to be higher after exposure
      to multimodal therapy compared with RT alone. Continued follow-up of survivors as
      they age is essential.

PMID- 25395464
TI  - MGMT methylation in glioblastoma: tale of the tail.

PMID- 25395463
TI  - White matter compromise predicts poor intellectual outcome in survivors of
      pediatric low-grade glioma.
AB  - BACKGROUND: While the impact of cranial radiation on white matter following
      treatment for pediatric brain tumor has been the focus of many recent studies,
      the effect of treatment in the absence of radiation has received little
      attention. The relations between white matter and cognitive outcome have not been
      explored in patients who have undergone radiation-free treatment. As most
      patients treated without cranial radiation survive long after their diagnosis, it
      is critical to identify factors that may impact structural and neurocognitive
      outcomes. METHODS: Using diffusion tensor imaging, we examined white matter
      structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with
      subtentorial location and 13 with supratentorial location) and 32 healthy
      participants. Indices of intellectual functioning were also evaluated. Radiation
      was not used to treat this cohort, aged 8-19 years. RESULTS: We detected evidence
      of deficits in IQ and compromised supra- and subtentorial white matter in
      patients relative to healthy children (P < .05). Compromise of supratentorial
      white matter mediated the impact of treatment for PLGG on IQ. Greater white
      matter compromise was observed in patients who presented without multiple
      symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1
      status, were younger age at diagnosis, and whose parents had lower levels of
      education (P < .05). CONCLUSIONS: Our findings provide evidence of increased risk
      of intellectual and white matter compromise in patients treated for PLGG without
      radiation. We identify a neural origin of cognitive deficit useful for predicting
      outcome and mitigating long-term adverse effects in pediatric brain tumor
      patients treated without cranial radiation.

PMID- 25395465
TI  - Extrauterine fibroids: a diagnostic challenge and a long-term battle.
AB  - Extrauterine fibroids often present a diagnostic challenge due to the unusual
      locations they arise from. We present a series of rare extrauterine fibroids. In
      recent years, these fibroids have been associated with previous morcellated
      hysterectomies or myomectomies. Our series of six patients were found to have
      extrauterine fibroids (confirmed through histology) and underwent open
      hysterectomy and open or laparoscopic myomectomy. Four had undergone previous
      laparoscopic myomectomies while the other two had no previous intra-abdominal
      surgeries. Postsurgical occurrence may be caused by incomplete removal of
      morcellated fibroid tissue. Spontaneous occurrence can be associated with
      congenital Mullerian system defects. Extrapolating from this hypothesis, we
      recommend physicians to make sure that counselling for extrauterine seeding and
      dissemination of unexpected malignancy is undertaken in cases of minimally
      invasive surgeries where morcellation is expected. Long-term tumour surveillance
      is thus essential in such instances. 

PMID- 25395466
TI  - A case of ureteric injury postappendectomy presenting as ureterocutaneous
      fistula.
AB  - Ureteric injuries, although uncommon, are a potential complication in pelvic and
      gynaecological surgeries and can have serious implications. The risk is mainly
      related to the complexity of the surgical procedure and the presence of eventual
      periureteric pathology. Ureteric injury during appendectomy is rare. The ureter
      may be damaged by laceration, being crushed, or thermal or ischaemic injury. The
      retrocaecal appendix, due to its proximity to the ureter, may also get
      accidentally injured. The most effective measure to prevent iatrogenic injury is
      to have a sound knowledge of abdominal and pelvic anatomy, meticulous surgical
      technique and an identification of factors that increase the likelihood of
      developing such complications. 

PMID- 25395467
TI  - Lung cancer masquerading as breast cancer with carcinoma en cuirasse.
AB  - Metastases to the breast from lung cancer are rare. Carcinoma en cuirasse is an
      unusual form of metastatic cutaneous carcinoma, almost exclusively described as
      deposits secondary to breast carcinoma. A 63-year-old woman presented with
      dyspnoea. A CT scan demonstrated a pleural effusion, large pericardial effusion,
      mediastinal lymphadenopathy and right basal consolidation. Pleural fluid cytology
      and immunohistochemistry were consistent with a diagnosis of primary lung
      adenocarcinoma. The patient was treated with pemetrexed and carboplatin,
      resulting in stable disease. A year later, she developed bilateral breast masses
      and multiple painful erythematous subcutaneous nodules over her torso, clinically
      indistinguishable from carcinoma en cuirasse. A biopsy demonstrated these were
      deposits from metastatic adenocarcinoma of the lung. The patient received
      docetaxel and carboplatin with initial good response. The painful lesions were
      subsequently treated with radiotherapy, which provided symptomatic relief. To the
      best of our knowledge, this is the only case of metastatic lung adenocarcinoma
      mimicking carcinoma en cuirasse. 

PMID- 25395468
TI  - Steroid-induced scleroderma renal crisis in an at-risk patient.
AB  - Scleroderma renal crisis (SRC) is a major complication of systemic sclerosis
      (SSc). We present a case of a patient who died of complications attributable to
      SRC in the context of recently diagnosed SSc. We review the typical clinical and
      laboratory features of SSc present in our patient and highlight those that
      identify greater risk of progression to SRC. Particular risk factors for SRC
      include cutaneous involvement, positive anti-RNA polymerase III antibodies and
      use of corticosteroids (CS). The authors emphasise the importance of risk
      evaluation when choosing to use CS in patients with SSc. 

PMID- 25395469
TI  - Eye disorders in newborn infants (excluding retinopathy of prematurity).
AB  - A screening eye examination is an essential part of the newborn assessment. The
      detection of many ocular disorders in newborn infants can be achieved through
      careful observation of the infant's visual behaviour and the use of a direct
      ophthalmoscope to assess the ocular structures and check the red reflex. Early
      diagnosis and subspecialty referral can have a critical impact on the prognosis
      for many ocular conditions, including potentially blinding but treatable
      conditions such as congenital cataracts, life-threatening malignancies such as
      retinoblastoma and harbingers of disease elsewhere such as sporadic aniridia and
      its association with the development of Wilms tumour.

PMID- 25395470
TI  - Decreasing mean airway pressure as a management strategy for tension
      pneumatocoeles.

PMID- 25395471
TI  - Bipolar disorder comorbid with borderline personality disorder and treatment with
      mood stabilisers.

PMID- 25395472
TI  - Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood
      acute lymphoblastic leukemia.
AB  - BACKGROUND: Several studies suggest that maternal folic acid supplementation
      before or during pregnancy protects against childhood acute lymphoblastic
      leukemia (ALL). We investigated associations between ALL risk and folate pathway
      gene polymorphisms, and their modification by maternal folic acid supplements, in
      a population-based case-control study (2003-2007). METHODS: All Australian
      pediatric oncology centers provided cases; controls were recruited by national
      random digit dialing. Data from 392 cases and 535 controls were included. Seven
      folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR
      2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in
      children and their parents. Information on prepregnancy maternal folic acid
      supplement use was collected. ORs were estimated with unconditional logistic
      regression adjusted for frequency-matched variables and potential confounders.
      Case-parent trios were also analyzed. RESULTS: There was some evidence of a
      reduced risk of ALL among children who had, or whose father had, the MTRR 66GG
      genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI,
      0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were
      1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by
      maternal folic acid supplementation. CONCLUSIONS: Some folate pathway gene
      polymorphisms in the child or a parent may influence ALL risk. While biologically
      plausible, underlying mechanisms for these associations need further elucidation.
      IMPACT: Folate pathway polymorphisms may be related to risk of childhood ALL, but
      larger studies are needed for conclusive results.

PMID- 25395473
TI  - The Arabidopsis cytosolic Acyl-CoA-binding proteins play combinatory roles in
      pollen development.
AB  - In Arabidopsis, six acyl-CoA-binding proteins (ACBPs) have been identified and
      they have been demonstrated to function in plant stress responses and
      development. Three of these AtACBPs (AtACBP4-AtACBP6) are cytosolic proteins and
      all are expressed in floral organs as well as in other tissues. The roles of
      cytosolic AtACBPs in floral development were addressed in this study. To this
      end, a T-DNA insertional knockout mutant of acbp5 was characterized before use in
      crosses with the already available acbp4 and acbp6 T-DNA knockout mutants to
      examine their independent and combinatory functions in floral development. The
      single-gene knockout mutations did not cause any significant phenotypic changes,
      while phenotypic deficiencies affecting siliques and pollen were observed in the
      double mutants (acbp4acbp6 and acbp5acbp6) and the acbp4acbp5acbp6 triple mutant.
      Vacuole accumulation in the acbp4acbp6, acbp5acbp6 and acbp4acbp5acbp6 pollen was
      the most severe abnormality occurring in the double and triple mutants.
      Furthermore, scanning electron microscopy and transmission electron microscopy
      revealed exine and oil body defects in the acbp4acbp5acbp6 mutant, which also
      displayed reduced ability in in vitro pollen germination. Transgenic Arabidopsis
      expressing beta-glucuronidase (GUS) driven from the various AtACBP promoters
      indicated that AtACBP6pro::GUS expression overlapped with AtACBP4pro::GUS
      expression in pollen grains and with AtACBP5pro::GUS expression in the
      microspores and tapetal cells. Taken together, these results suggest that the
      three cytosolic AtACBPs play combinatory roles in acyl-lipid metabolism during
      pollen development. 

PMID- 25395474
TI  - A more encouraging future for hospitals?

PMID- 25395475
TI  - What the MAYSI-2 Can Tell Us About Anger-Irritability and Trauma.
AB  - The rate of experiencing trauma can be quite high for juvenile offenders and
      those experiences can lead to feelings of anger and irritability. This study uses
      Massachusetts Youth Screening Instrument-Version 2 (MAYSI-2) data to examine the
      relationship between the Traumatic Experiences (TE) and Angry-Irritable (AI)
      scales for juvenile offenders (N = 1,348) from a Midwest detention center. Chi
      square analyses revealed statistically significant relationships between the AI
      scale and gender, race, and the TE scale. In addition, ordinal logistic
      regression results showed that as the number of traumatic experiences increased,
      so did the odds of scoring Caution or Warning on the AI scale. Recommendations
      are that juvenile justice systems utilize a trauma-informed process throughout
      the adjudicatory process and there be improved efforts to coordinate services
      across multiple systems, such as child welfare and special education, where
      juvenile offenders are often engaged. 

PMID- 25395476
TI  - The Influence of Culture-Specific Personality Traits on the Development of
      Delinquency in At-Risk Youth.
AB  - The association between culture-specific personality variables and family
      factors, and juvenile delinquency, was assessed in a sample of 402 adolescents of
      Chinese ethnicity between 12 and 17 years of age (Mage = 15.13, SD = 1.41; 135
      girls), a subgroup of whom were considered at risk for juvenile delinquency owing
      to addictive behavior tendencies. Culture-specific personality variables were
      assessed using the Chinese Personality Assessment Inventory-Adolescent version
      Interpersonal Relatedness factor. The General Function subscale of the Chinese
      version of the Family Assessment Device was utilized to assess the influence of
      perceived levels of family functioning. Both culture-specific personality
      variables and non-culture-specific familial factors were significantly and
      negatively associated with self-reported juvenile delinquency (p < .001).
      However, in a sample of at-risk adolescents, only a culture-specific variable
      measuring orientation toward the family was able to predict self-reported
      juvenile delinquency (p < .001). Implications of the current results are
      discussed. 

PMID- 25395477
TI  - Eliciting Responsivity: Exploring Programming Interests of Federal Inmates as a
      Function of Security Classification.
AB  - Research supports the effectiveness of the Risk-Needs-Responsivity model for
      reducing criminal recidivism. Yet programming interests of inmates--one facet of
      responsivity--remain an understudied phenomenon. In the present study, we
      explored the programming interests of 753 federal inmates housed across three
      levels of security. Results suggest that inmates, as a group, prefer specific
      programs over others, and that some of their interests may differ by security
      level. We discuss possible implications of these findings.

PMID- 25395478
TI  - The Development and Validation of an Actuarial Risk Assessment Tool for the
      Prediction of First-Time Offending.
AB  - For prevention purposes, it is important that police officers can estimate the
      risk for delinquency among juveniles who were involved in a criminal offense, but
      not in the role of a suspect. In the present study, the Youth Actuarial Risk
      Assessment Tool for First-Time Offending (Y-ARAT-FO) was developed based solely
      on police records with the aim to enable Dutch police officers to predict the
      risk for first-time offending. For the construction of this initial screening
      instrument, an Exhaustive Chi-squared Automatic Interaction Detector (Exhaustive
      CHAID) analysis was performed on a data set that was retrieved from the Dutch
      police system. The Y-ARAT-FO was developed on a sample of 1,368 juveniles and
      validated on a different sample of 886 juveniles showing moderate predictive
      accuracy in the validation sample (area under the receiver operating
      characteristic curve [AUC] = .728). The predictive accuracy of the Y-ARAT-FO was
      considered sufficient to justify its use as an initial screening instrument by
      the Dutch police. 

PMID- 25395479
TI  - Dystonia in children and adolescents: a systematic review and a new diagnostic
      algorithm.
AB  - Early aetiological diagnosis is of paramount importance for childhood dystonia
      because some of the possible underlying conditions are treatable. Numerous
      genetic and non-genetic causes have been reported, and diagnostic workup is often
      challenging, time consuming and costly. Recently, a paradigm shift has occurred
      in molecular genetic diagnostics, with next-generation sequencing techniques now
      allowing us to analyse hundreds of genes simultaneously. To ensure that patients
      benefit from these new techniques, adaptation of current diagnostic strategies is
      needed. On the basis of a systematic literature review of dystonia with onset in
      childhood or adolescence, we propose a novel diagnostic strategy with the aim of
      helping clinicians determine which patients may benefit by applying these new
      genetic techniques and which patients first require other investigations. We also
      provide an up-to-date list of candidate genes for a dystonia gene panel, based on
      a detailed literature search up to 20 October 2014. While new genetic techniques
      are certainly not a panacea, possible advantages of our proposed strategy include
      earlier diagnosis and avoidance of unnecessary investigations. It will therefore
      shorten the time of uncertainty for patients and their families awaiting a
      definite diagnosis. 

PMID- 25395480
TI  - Do electronic cigarettes help with smoking cessation?
AB  - Smoking causes around 100,000 deaths each year in the UK, and is the leading
      cause of preventable disease and early mortality. Smoking cessation remains
      difficult and existing licensed treatments have limited success. Nicotine
      addiction is thought to be one of the primary reasons that smokers find it so
      hard to give up, and earlier this year DTB reviewed the effects of nicotine on
      health. Electronic cigarettes (e-cigarettes) are nicotine delivery devices that
      aim to mimic the process of smoking but avoid exposing the user to some of the
      harmful components of traditional cigarettes. However, the increase in the use of
      e-cigarettes and their potential use as an aid to smoking cessation has been
      subject to much debate. In this article we consider the regulatory and safety
      issues associated with the use of e-cigarettes, and their efficacy in smoking
      cessation and reduction.

PMID- 25395481
TI  - ?Bedaquiline for multidrug-resistant tuberculosis.
AB  - Resistance to drugs used to treat tuberculosis (TB) is a major public health
      problem that threatens progress made in TB management and control worldwide. It
      may result from improper use of antibiotics, including prescription of non
      standard treatment regimens and poor adherence to drug therapy. Multidrug
      resistant TB (MDR-TB) is defined as resistance to isoniazid and rifampicin, with
      or without resistance to other first-line drugs. Extensively drug-resistant TB
      (XDR-TB) refers to resistance to at least isoniazid and rifampicin, and to any
      fluoroquinolone, and to any of the three second-line injectables  (amikacin,
      capreomycin and kanamycin). In 2012, DTB discussed the investigation, management
      and treatment of patients with MDR- and XDR-TB. Earlier this year, ?bedaquiline
      (Sirturo) and ?delamanid (Deltyba) were authorised by the European Medicines
      Agency (EMA) under its 'conditional market authorisation' scheme for use as part
      of an appropriate combination regimen for pulmonary MDR-TB in adult patients
      "when an effective treatment regimen cannot otherwise be composed for reasons of
      resistance or tolerability." In this article, we review the evidence for
      bedaquiline in the management of MDR-TB.

PMID- 25395482
TI  - An abnormal chest radiograph.

PMID- 25395483
TI  - Efficacy of intravitreal injection of aflibercept in neovascular age-related
      macular degeneration with or without choroidal vascular hyperpermeability.
AB  - PURPOSE: To compare therapeutic responses to intravitreal aflibercept and
      ranibizumab in neovascular age-related macular degeneration (AMD)-affected eyes
      with and without choroidal vascular hyperpermeability (CVH). METHODS: Medical
      records of 216 consecutive patients (216 eyes) with treatment-naive exudative AMD
      who had received three monthly intravitreal injections of aflibercept (2 mg) and
      ranibizumab (0.5 mg) at a single institution were analyzed. The associations of
      CVH with functional and morphologic changes were compared between the treatment
      groups. RESULTS: Although foveal thickness (P = 0.85) and visual acuity (P =
      0.13) changes were not significantly different between the treatment groups,
      subfoveal choroidal thickness (CT) (P = 0.001) and pigment epithelial detachment
      (PED) height (P = 0.043) decreased more profoundly in the aflibercept-treated
      group. The incidence of dry macula after treatments was lower in the ranibizumab
      treated eyes with CVH than in those without CVH (P = 0.043), but it showed no
      significant difference between the aflibercept-treated eyes with and without CVH
      (P = 0.74). The aflibercept-treated eyes with CVH showed a higher incidence of
      dry macula (P = 0.04) and greater decrease in subfoveal CT (P = 0.002) than the
      ranibizumab-treated eyes with CVH. CONCLUSIONS: Intravitreal aflibercept can
      achieve remission of exudative retinal changes in eyes with AMD even in the
      presence of CVH. In addition, it showed greater effects on the choroid and PED
      than intravitreal ranibizumab. The possible relationship between CVH suppression
      and decrease in CT warrants further study.

PMID- 25395485
TI  - Retinal and choroidal changes with severe hypertension and their association with
      visual outcome.
AB  - PURPOSE: To investigate retinal and choroidal changes using spectral-domain
      optical coherence tomography (SD-OCT) and to evaluate visual outcome in patients
      with severe hypertension. METHODS: In 42 eyes with hypertensive retinopathy from
      21 patients with severe hypertension (systolic blood pressure [SBP] >= 180 mm Hg
      or diastolic blood pressure [DBP] >= 110 mm Hg), SD-OCT was performed on the day
      blood pressure (BP) was measured. Best-corrected visual acuity (BCVA), fundus
      features, and SD-OCT morphologic findings were evaluated and OCT features were
      compared between baseline and final visits. Associations between clinical
      findings, OCT image features, and Keith-Wagener-Barker (KWB) hypertensive
      retinopathy grades and baseline and final BCVA were examined. RESULTS: Optical
      coherence tomography findings included macular edema (central macular thickness >
      300 MUm), irregularly reflective regions, retinal nerve fiber layer thickening,
      subretinal fluid (SRF), intraretinal fluid, and intraretinal hyperreflective
      dots. All abnormalities rapidly resolved with BP control except for the
      hyperreflective dots. Central macular thickness, subfoveal choroidal thickness
      (SCT), and SRF height significantly decreased following BP control. Subretinal
      fluid height was significantly correlated with baseline BCVA, final BCVA, and
      SCT. Based on fundoscopic and OCT features, eyes were classified as showing mild
      to moderate retinopathy, malignant retinopathy without SRF, and malignant
      retinopathy with SRF. Unlike KWB grades (P = 0.077), the OCT-based retinopathy
      grades were significantly correlated to final BCVA, as shown by linear regression
      analyses (P = 0.025). CONCLUSIONS: Severe hypertension resulted in exudative
      retinal and choroidal changes, characterized by SRF accumulation and increased
      SCT. Our grading system may represent retinopathy severity and predict visual
      outcome better than the KWB grading system in patients with severe hypertension.

PMID- 25395484
TI  - Cytokine production and antigen recognition by human mucosal homing conjunctival
      effector memory CD8+ T cells.
AB  - PURPOSE: Conjunctival epithelial T cells are dominated by CD3(+)CD56
      TCRalphabeta(+)CD8alphabeta(+) lymphocytes. In this study we explored the antigen
      experience status, mucosal homing phenotype, cytokine expression, and viral
      antigen recognition of conjunctival epithelial CD8(+) T cells from healthy
      individuals. METHODS: Following ocular surface impression cytology, conjunctival
      cells were recovered by gentle agitation and analyzed by flow cytometry for cell
      surface markers, cytokine production (stimulated by phorbol 12-myristate 13
      acetate [PMA]/ionomycin), and Epstein-Barr virus (EBV)/cytomegalovirus (CMV)
      immunodominant epitope recognition using major histocompatibility complex (MHC)
      class I peptide tetramers. RESULTS: In contrast to peripheral blood, conjunctival
      epithelial CD8(+) T cells were dominantly CD45RA(-)CCR7(-) effector memory cells,
      and the vast majority expressed the mucosal homing integrin alphaEbeta7.
      Conjunctival memory CD8(+) T cells maintained effector functions with the ability
      to secrete IFN-gamma and expression of Granzyme B, although they expressed
      significantly reduced amounts per cell compared to peripheral blood T cells.
      Interestingly, herpetic virus-specific CD8(+) T cells recognizing epitopes
      derived from EBV and CMV could be detected in the conjunctival cells of healthy
      virus carriers, although they were generally at lower frequencies than in the
      peripheral blood of the same donor. Virus-specific conjunctival CD8(+) T cells
      were dominated by CD45RA(-)CCR7(-) effector memory cells that expressed
      alphaEbeta7. CONCLUSIONS: These data demonstrate that the majority of
      conjunctival epithelial CD8(+) T cells are mucosal homing alphaEbeta7(+) effector
      memory T cells, which can recognize viral epitopes and are capable of secreting
      Granzyme B and IFN-gamma.

PMID- 25395486
TI  - Shear stress-triggered nitric oxide release from Schlemm's canal cells.
AB  - PURPOSE: Endothelial nitric oxide (NO) synthase is regulated by shear stress. At
      elevated intraocular pressures when the Schlemm's canal (SC) begins to collapse,
      shear stress is comparable with that in large arteries. We investigated the
      relationship between NO production and shear stress in cultured human SC cells.
      METHODS: Schlemm's canal endothelial cells isolated from three normal and two
      glaucomatous human donors were seeded into Ibidi flow chambers at confluence,
      cultured for 7 days, and subjected to steady shear stress (0.1 or 10 dynes/cm(2))
      for 6, 24, or 168 hours. Cell alignment with flow direction was monitored, and NO
      production was measured using 4-amino-5-methylamino-2',7'-difluorofluorescein
      (DAF-FM) and Griess reagents. Human trabecular meshwork (TM) and umbilical vein
      endothelial cells (HUVECs) were used as controls. RESULTS: Normal SC strains
      aligned with the direction of flow by 7 days. Comparing 0.1 vs. 10 dynes/cm(2),
      NO levels increased by 82% at 24 hours and 8-fold after 7 days by DAF-FM, and
      similar results were obtained with Griess reagent. Shear responses by SC cells at
      24 hours were comparable with HUVECs, and greater than TM cells, which appeared
      shear-insensitive. Nitric oxide production by SC cells was detectable as early as
      6 hours and was inhibited by 100 MUM nitro-L-arginine methyl ester. Two
      glaucomatous SC cell strains were either unresponsive or lifted from the plate in
      the face of shear. CONCLUSIONS: Shear stress triggers NO production in human SC
      cells, similar to other vascular endothelia. Increased shear stress and NO
      production during SC collapse at elevated intraocular pressures may in part
      mediate IOP homeostasis.

PMID- 25395487
TI  - Foveal contour changes following surgery for idiopathic epiretinal membrane.
AB  - PURPOSE: We evaluated the change in foveal contour in eyes with idiopathic
      epiretinal membrane (ERM) before and four months following pars plana vitrectomy
      with internal limiting and epiretinal membrane peeling, and correlated foveal
      contour with best corrected visual acuity (BCVA) and optical coherence tomography
      (OCT) parameters. METHODS: Retrospective chart review of consecutive patients
      undergoing surgery with pre- and postoperative OCT. Foveal contour grading was
      devised according to the thickness of the fovea relative to the surrounding
      macula from OCT radial line scans: Grade 0, foveal depression relative to
      surrounding macula; Grade 1, relative flatness; and Grade 2, fovea thicker than
      surrounding macula. Baseline and follow-up grades were compared for change and
      correlated with BCVA, central retinal thickness (CRT), central subfield thickness
      (CST), central subfield volume (CSV), and integrity of the ellipsoid zone (EZ).
      RESULTS: Among 41 eyes of 41 patients, mean follow-up was 125 days. No eyes were
      Grade 0 at baseline; 7 of 41 eyes were Grade 0 at follow-up. Baseline Grade 1
      eyes improved CRT (P < 0.001), CST (P < 0.001), CSV (P = 0.002), and BCVA (P =
      0.022). Baseline Grade 2 eyes improved CRT (P < 0.001), CST (P < 0.001), and CSV
      (P < 0.001), but not BCVA (P = 0.369). CONCLUSIONS: We developed a novel foveal
      contour grading method to assess retinal contour in ERM eyes before and after
      surgery. In eyes with ERM and no foveal depression, the majority did not regain
      foveal depression following surgery even though retinal thickness improved.

PMID- 25395489
TI  - Some cancer waits and pressure on elective waiting times are caused by lack of
      money, MPs hear.

PMID- 25395488
TI  - The driving visual field and a history of motor vehicle collision involvement in
      older drivers: a population-based examination.
AB  - PURPOSE: We designed a visual field test focused on the field utilized while
      driving to examine associations between field impairment and motor vehicle
      collision involvement in 2000 drivers aged 70 years or older. METHODS: The
      "driving visual field test" involved measuring light sensitivity for 20 targets
      in each eye, extending 15 degrees  superiorly, 30 degrees  inferiorly, 60 degrees
      temporally, and 30 degrees  nasally. The target locations were selected on the
      basis that they fell within the field region utilized when viewing through the
      windshield of a vehicle or viewing the dashboard while driving. Monocular fields
      were combined into a binocular field based on the more sensitive point from each
      eye. Severe impairment in the overall field or a region was defined as average
      sensitivity in the lowest quartile of sensitivity. At-fault collision involvement
      for 5 years prior to enrollment was obtained from state records. Poisson
      regression was used to calculate crude and adjusted rate ratios (RRs) examining
      the association between field impairment and at-fault collision involvement.
      RESULTS: Drivers with severe binocular field impairment in the overall driving
      visual field had a 40% increased rate of at-fault collision involvement (RR,
      1.40; 95% confidence interval [CI]: 1.07-1.83). Impairment in the lower and left
      fields was associated with elevated collision rates (RR, 1.40; 95% CI: 1.07-1.82
      and RR, 1.49; 95% CI: 1.15-1.92, respectively), whereas impairment in the upper
      and right field regions was not. CONCLUSIONS: Results suggest that older drivers
      with severe impairment in the lower or left region of the driving visual field
      are more likely to have a history of at-fault collision involvement.

PMID- 25395490
TI  - The grossly "rusty" tumor of breast: invasive ductal carcinoma with osteoclast
      like giant cells.

PMID- 25395491
TI  - The Morchella esculenta of the digestive tract.

PMID- 25395492
TI  - The yolk sac tumor: reflections on a remarkable neoplasm and two of the many
      intrigued by it-Gunnar Teilum and Aleksander Talerman-and the bond it formed
      between them.
AB  - One of the most remarkable of human neoplasms, the yolk sac tumor, is reviewed,
      emphasizing its histologic diversity and differential diagnosis, occurrence at
      many sites, and the shared passion for this unique neoplasm of Dr Gunnar Teilum
      (who deserves almost all credit for delineation of the nature of the tumor and
      its features) and Dr Aleksander Talerman (who made his own contribution to our
      knowledge of it) and the friendship it helped forge between these 2 distinguished
      pathologists. In a unique series of articles, beginning in the early 1940s,
      Teilum delineated the distinctive features of the neoplasm and recognized that it
      was 1 of 2 initially included as "mesonephroma ovarii" by Dr Walter Schiller in
      1939 (the second we now know as clear cell carcinoma). Teilum named the tumor
      "endodermal sinus tumor" because it came to his attention that papillary
      formations common in the yolk sac tumor resembled the endodermal sinuses of the
      rat placenta. He focused on the histogenesis of the tumor and its morphologic
      features culminating in a classic paper in Cancer in 1959. Although Teilum and
      others recognized that yolk sac tumor could be a component of mixed germ cell
      tumors, Talerman was one of the first to emphasize that, particularly in the
      testis, it was common to see yolk sac tumor as a component of a mixed germ cell
      tumor. Teilum, working in Copenhagen, and Talerman, when the former was alive,
      working in Rotterdam, developed a warm friendship in part due to their great
      interest in the yolk sac tumor, although it also extended to other areas of
      gonadal neoplasia and indeed beyond the boundaries of medicine when they shared
      time together. The typical histologic features of the yolk sac tumor are the
      reticular-microcystic patterns Teilum described, but various other patterns,
      including solid and even rarer ones such as glandular and hepatoid, are now well
      known. There are some interesting variations in the age distribution of this
      tumor at various sites: for example, vaginal examples are almost restricted to
      children under 2 years of age; those of the testis that are pure also occur
      mostly in young boys (average age about 20 months) but are occasionally seen in
      later years; ovarian examples peak at about 19 years of age; mediastinal forms
      are mostly restricted to young adult males. Brief consideration is also given to
      the occurrence of this tumor at well-known extragonadal sites such as
      retroperitoneum, mediastinum, and pineal as well as more exotic locations. Note
      is made of the recently emphasized occurrence of the yolk sac tumor on the
      background of a somatic neoplasm, most often endometrioid carcinoma of the ovary.
      Given the wide ranging and fascinating clinical and pathologic aspects of the
      neoplasm, it is no surprise that it continues to be a source of great interest to
      any pathologist who sees one or more examples, and we are indebted to Dr Teilum
      for his monumental studies and to Dr Talerman for his own contributions. 

PMID- 25395493
TI  - How to use: the direct antiglobulin test in newborns.
AB  - The direct antiglobulin test (DAT) detects the presence of immunoglobulin,
      complement or both bound to the red blood cell membrane. The test, historically
      called the 'Coombs test', was first described in 1945 by Cambridge immunologist
      Robin Coombs. Suspected haemolytic disease of the newborn, due to either Rhesus
      disease or ABO incompatibility, is one of most common reasons for requesting a
      DAT in newborns. In this article, we discuss the physiological background and
      technological background of the DAT. We also provide a clinical framework for a
      rational approach to the use and interpretation of the DAT in newborns. 

PMID- 25395494
TI  - The diagnosis and management of acute otitis media: American Academy of
      Pediatrics Guidelines 2013.

PMID- 25395495
TI  - India healthcare experts worry that health minister's exit may affect public
      health initiatives.

PMID- 25395496
TI  - Impact of sodium arsenite on chromosomal aberrations with respect to
      polymorphisms of detoxification and DNA repair genes.
AB  - Arsenic compounds can increase production of reactive oxygen species. Reactive
      oxygen species can induce double-strand breaks in DNA, which is a cause of
      chromosome aberrations (CAs). This study was conducted to determine the
      association between arsenic exposure and polymorphisms of genes involved in
      detoxification (glutathione S-transferase T1 [GSTT1], glutathione S-transferase
      M1 [GSTM1], glutathione S-transferase O2 [GSTO2], catalase [CAT], and NAD(P)H
      quinone oxidoreductase1 [NQO1]) as well as nonhomologous end joining DNA repair
      genes (XRCC4, XRCC5, and XRCC6) with induction of chromosomal aberrations. The
      participants consisted of 123 healthy males who were genotyped using polymerase
      chain reaction-based methods. Primary cultures of whole blood were treated with
      sodium arsenite (NaAsO(2); iAs(III); at final concentration 1 umol/L), mitomycin
      C (at final concentration 60 etag/mL; as positive control), or untreated. For
      each culture, mitotic index (MI), chromatid breaks (CBs), CAs, and total
      percentage of aberrant cells were determined. The levels of CB and percentage of
      aberrant cells were significantly higher in the TT genotype of CAT (C-262T
      polymorphism) than the CC genotype. The CB value in samples with GSTM1 active
      genotype was significantly higher than the null genotype. The MI in samples with
      TT genotype of NQO1 (C609T polymorphism) was significantly higher than MI in
      samples having CC and CT genotypes. There was no association between MI, CB, CA,
      and percentage of aberrant cells and polymorphisms of XRCC4, XRCC5, and XRCC6.

PMID- 25395497
TI  - The Effect of Glycated Hemoglobin and Albumin-Corrected Glycated Serum Protein on
      Mortality in Diabetic Patients Receiving Continuous Peritoneal Dialysis.
AB  - OBJECTIVE: To explore the effect of glycated hemoglobin (HbA1c) and albumin
      corrected glycated serum proteins (Alb-GSP) on the mortality of diabetic patients
      receiving continuous peritoneal dialysis (PD). METHODS: In this single-center
      retrospective cohort study, incident diabetic PD patients from January 1, 2006,
      to December 31, 2010, were recruited, and followed up until December 31, 2011.
      The effect of HbA1c and Alb-GSP on mortality was evaluated by Cox proportional
      hazards models. RESULTS: A total of 200 patients (60% male, mean age 60.3 +/-
      10.6 years) with a mean follow-up of 29.0 months (range: 4.3 - 71.5 months) were
      recruited. Sixty-four patients died during the follow-up period, of whom 21 died
      of cardiovascular disease (CVD). Mean values for HbA1c, GSP and Alb-GSP were 6.7%
      (range: 4.1 - 12.5%), 202 MUmol/L (range: 69 - 459 MUmol/L), and 5.78 MUmol/g
      (range: 2.16 - 14.98 MUmol/g), respectively. The concentrations of GSP and Alb
      GSP were closely correlated with HbA1c (r = 0.41, p < 0.001 and r = 0.45, p <
      0.001, respectively). In multivariate Cox proportional hazards models, patients
      with HbA1c >= 8% were associated with increased risk of all-cause mortality
      (hazard ratio [HR] = 2.29, 95% confidence interval [CI]: 1.06 - 4.96, p = 0.04),
      but no increased mortality in patients with 6.0% <= HbA1c <= 7.9%. Patients with
      Alb-GSP <= 4.50 MUmol/g had increased all-cause and non-cardiovascular mortality
      (HR = 2.42, 95% CI: 1.13 - 5.19, p = 0.02; and HR = 2.98, 95% CI: 1.05 - 8.48, p
      = 0.04 respectively). CONCLUSIONS: Increased HbA1c and decreased Alb-GSP may be
      associated with poorer survival in diabetic PD patients, with a non-significant
      trend observed for poorer survival with the highest level of Alb-GSP.

PMID- 25395498
TI  - The Mutual Relationship Between Peritonitis and Peritoneal Transport.
AB  - ? BACKGROUND: Preservation of the peritoneum is required for long-term peritoneal
      dialysis (PD). We investigated the effect of multiple peritonitis episodes on
      peritoneal transport. ? METHODS: Prospectively collected data from 479 incident
      PD patients treated between 1990 and 2010 were analyzed, using strict inclusion
      criteria: follow-up of at least 3 years with the availability of a Standard
      Peritoneal Permeability Analysis (SPA) in the first year after start of PD and
      within the third year of PD, without peritonitis preceding the first SPA. For the
      purpose of the study, we only included patients who remained peritonitis-free (n
      = 28) or who experienced 3 or more peritonitis episodes (n = 16). ? RESULTS: At
      baseline the groups were similar with regard to small solute and fluid transport.
      However, the frequent peritonitis group had lower peritoneal protein clearances
      compared to the no peritonitis group, resulting in lower dialysate concentrations
      of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and
      alpha-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in
      serum concentrations were present. A comparison between the transport slopes over
      time in both groups showed a positive time trend of mass transfer area
      coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a
      negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the
      no peritonitis group. Frequent peritonitis did not affect free water transport. ?
      CONCLUSIONS: Slow initial peritoneal transport rates of serum proteins result in
      lower dialysate concentrations, and likely a lower opsonic activity, which is a
      risk factor for peritonitis. Patients with frequent peritonitis show an increase
      in small solute transport and a concomitant decrease of ultrafiltration. In long
      term peritonitis-free PD patients, small solute transport decreased, while
      ultrafiltration increased. This suggests that frequent peritonitis leads to an
      increase of the vascular peritoneal surface area without all the structural
      membrane alterations that may develop after long-term PD.

PMID- 25395501
TI  - Indian doctors are divided over plan to allow traditional medicine practitioners
      to perform abortions.

PMID- 25395499
TI  - The Role of NGAL in Peritoneal Dialysis Effluent in Early Diagnosis of
      Peritonitis: Case-Control Study in Peritoneal Dialysis Patients.
AB  - BACKGROUND: Peritoneal dialysis (PD) is frequently complicated by high rates of
      peritonitis, which result in hospitalization, technique failure, transfer to
      hemodialysis, and increased mortality. Early diagnosis, and identification of
      contributing factors are essential components to increasing effectiveness of
      care. In previous reports, neutrophil gelatinase-associated lipocalin (NGAL), a
      lipocalin which is a key player in innate immunity and rapidly detectable in
      peritoneal dialysis effluent (PDE), has been demonstrated to be a useful tool in
      the early diagnosis of peritonitis. This study investigates predictive value of
      PDE NGAL concentration as a prognostic indicator for PD-related peritonitis.
      METHODS: A case-control study with 182 PD patients was conducted. Plasma and PDE
      were analyzed for the following biomarkers: C-reactive protein (CRP), blood
      procalcitonin (PCT), leucocytes and NGAL in PDE. The cases consisted of patients
      with suspected peritonitis, while controls were the patients who came to our
      ambulatory clinic for routine visits without any sign of peritonitis. The
      episodes of peritonitis were defined in agreement with International Society for
      Peritoneal Dialysis guidelines. Continuous variables were presented as the median
      values and interquartile range (IQR). Mann-Whitney U test was used to compare
      continuous variables. Univariate and multivariate logistic regression were used
      to evaluate the association of biomarkers with peritonitis. Receiver operating
      characteristic (ROC) curve analysis was used to calculate area under curve (AUC)
      for biomarkers. Finally we evaluated sensitivity, and specificity for each
      biomarker. All statistical analyses were performed with SPSS version 17.0 (SPSS
      Inc., Chicago, IL, USA). RESULTS: During the 19-month study, of the 182 patients,
      80 had a clinical diagnosis of peritonitis. C-reactive protein levels (p <
      0.001), PCT (p < 0.001), NGAL in PDE (p < 0.001), and white blood cells (WBC) in
      PDE (p < 0.001) were all significantly different in patients with and without
      peritonitis. In univariate analysis, CRP (odds ratio [OR] 1,339; p = 0.001), PCT
      (OR 2,473; p < 0,001), WBC in PDE (OR 3,986; p < 0,001), and NGAL in PDE (OR
      36.75 p < 0.001) were significantly associated with episodes of peritonitis. In
      multivariate regression analysis, only WBC (OR 24.84; p = 0,012), and peritoneal
      NGAL levels (OR 136.6; p = 0,01) were independent predictors of peritonitis
      events. Moreover, AUC for NGAL in peritoneal effluent was 0,936 (p < 0.001) while
      AUC for CRP, PCT, and WBC count in peritoneal effluent were 0,704 (p = 0.001),
      0.762 (p = 0.039), 0,975 (p < 0.001), respectively. Finally, combined WBC and
      peritoneal NGAL test increased the specificity (= 96%) of the single test.
      CONCLUSIONS: These results identify NGAL in peritoneal effluent as a reliable
      marker of peritonitis episodes in PD patients. Collectively, our findings
      demonstrate that the use of peritoneal NGAL cooperatively with current clinical
      diagnostic tools as a prognostic indicator, presents a valuable diagnostic tool
      in PD-associated peritonitis.

PMID- 25395500
TI  - Genetic Polymorphisms and Peritoneal Membrane Function.
AB  - BACKGROUND: Outcomes for peritoneal dialysis (PD) patients are affected by the
      characteristics of the peritoneal membrane, which may be determined by genetic
      variants. We carried out a systematic review of the literature to identify
      studies which assessed the association between genetic polymorphisms, peritoneal
      membrane solute transport, and clinical outcomes for PD patients. METHODS: The
      National Library of Medicine was searched using a variety of strategies. Studies
      which met our inclusion criteria were reviewed and data abstracted. Our outcomes
      of interest included: high transport status peritoneal membrane, risk for
      peritonitis, encapsulating peritoneal sclerosis (EPS), patient and technique
      survival. We combined data from studies which evaluated the same genetic
      polymorphism and the same outcome. RESULTS: We evaluated 18 relevant studies. All
      studies used a candidate gene approach. Gene polymorphisms in the interleukin
      (IL)-6 gene were associated with peritoneal membrane solute transport in several
      studies in different ethnic populations. Associations with solute transport and
      polymorphisms in endothelial nitric oxide synthase and receptor for advanced
      glycation end product genes were also identified. There was evidence of a genetic
      predisposition for peritonitis found in 2 studies, and for EPS in 1 study.
      Survival was found to be associated with a polymorphism in vascular endothelial
      growth factor and technique failure was associated with a polymorphism in the IL
      1 receptor antagonist. CONCLUSIONS: There is evidence that characteristics of the
      peritoneal membrane and clinical outcomes for PD patients have genetic
      determinants. The most consistent association was between IL-6 gene polymorphisms
      and peritoneal membrane solute transport.

PMID- 25395502
TI  - Myocardial performance is impaired in patients with branch retinal vein
      occlusion.
AB  - OBJECTIVE: To investigate whether the Tei index, which is an indicator of global
      myocardial function and an independent predictor of cardiac death, is increased
      in patients with branch retinal vein occlusion (BRVO). METHODS: The Tei index was
      used to evaluate myocardial performance, in addition to conventional
      echocardiographic evaluation of myocardial structural and functional changes, in
      patients with BRVO, patients with hypertension and healthy controls. RESULTS: Out
      of 36 patients with BRVO (18 female, 18 male; 17 hypertensive, 19 normotensive),
      29 patients with hypertension (15 female, 14 male) and 28 healthy controls (15
      female, 13 male), there were no significant between-group differences in age and
      sex. The mitral A wave was higher and mitral E/A ratio, mitral E wave and
      ejection time were lower, in patients with BRVO than in healthy controls. Mean
      Tei index was significantly higher in the BRVO group than in patients with
      hypertension or healthy controls. Compared with healthy controls, the Tei index
      was significantly higher in hypertensive and normotensive patients with BRVO.
      CONCLUSION: Myocardial performance is decreased in patients with BRVO,
      independent of whether or not they have hypertension.

PMID- 25395503
TI  - Explanatory trials versus pragmatic trials.

PMID- 25395504
TI  - More than 100 cancer experts attack Saatchi bill as potentially dangerous.

PMID- 25395507
TI  - Out of sight, out of mind.

PMID- 25395509
TI  - Seismology. Relief greets acquittals in Italy earthquake trial.

PMID- 25395510
TI  - Infectious diseases. Just one poliovirus left to go?

PMID- 25395512
TI  - Will pork be back on the menu?

PMID- 25395511
TI  - U.S. elections. For science, impact of Republican win may be muted.

PMID- 25395505
TI  - The Rho kinases: critical mediators of multiple profibrotic processes and
      rational targets for new therapies for pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung
      scarring, short median survival, and limited therapeutic options, creating great
      need for new pharmacologic therapies. IPF is thought to result from repetitive
      environmental injury to the lung epithelium, in the context of aberrant host
      wound healing responses. Tissue responses to injury fundamentally involve
      reorganization of the actin cytoskeleton of participating cells, including
      epithelial cells, fibroblasts, endothelial cells, and macrophages. Actin filament
      assembly and actomyosin contraction are directed by the Rho-associated coiled
      coil forming protein kinase (ROCK) family of serine/threonine kinases (ROCK1 and
      ROCK2). As would therefore be expected, lung ROCK activation has been
      demonstrated in humans with IPF and in animal models of this disease. ROCK
      inhibitors can prevent fibrosis in these models, and more importantly, induce the
      regression of already established fibrosis. Here we review ROCK structure and
      function, upstream activators and downstream targets of ROCKs in pulmonary
      fibrosis, contributions of ROCKs to profibrotic cellular responses to lung
      injury, ROCK inhibitors and their efficacy in animal models of pulmonary
      fibrosis, and potential toxicities of ROCK inhibitors in humans, as well as
      involvement of ROCKs in fibrosis in other organs. As we discuss, ROCK activation
      is required for multiple profibrotic responses, in the lung and multiple other
      organs, suggesting ROCK participation in fundamental pathways that contribute to
      the pathogenesis of a broad array of fibrotic diseases. Multiple lines of
      evidence therefore indicate that ROCK inhibition has great potential to be a
      powerful therapeutic tool in the treatment of fibrosis, both in the lung and
      beyond. 

PMID- 25395513
TI  - Scientific community. No sexism in science? Not so fast, critics say.

PMID- 25395515
TI  - Science and culture. The theoretical physicist behind Interstellar.

PMID- 25395514
TI  - Animal domestication. The genes that turned wildcats into kitty cats.

PMID- 25395516
TI  - Microbiology. Contamination plagues some microbiome studies.

PMID- 25395517
TI  - The river masters.

PMID- 25395518
TI  - Environmental science. The trouble with neonicotinoids.

PMID- 25395520
TI  - Astronomy. Improving planet-finding spectrometers.

PMID- 25395519
TI  - Human genetics. Hidden features of human hotspots.

PMID- 25395521
TI  - Developmental biology. Mesenchymal progenitor panoply.

PMID- 25395522
TI  - Paleoclimate. Did Antarctica initiate the ice age cycles?

PMID- 25395523
TI  - Synthetic biology. Dynamic genome engineering in living cells.

PMID- 25395524
TI  - Environmental economics. An economic perspective on the EPA's Clean Power Plan.

PMID- 25395525
TI  - Fauna in decline: a big leap to slavery.

PMID- 25395526
TI  - Fauna in decline: management risks.

PMID- 25395528
TI  - Fauna in decline: beyond extinction.

PMID- 25395527
TI  - Fauna in decline--response.

PMID- 25395529
TI  - Fauna in decline: the community way.

PMID- 25395530
TI  - Fauna in decline: protect forests now.

PMID- 25395532
TI  - Nanophotonics. Plasmoelectric potentials in metal nanostructures.
AB  - The conversion of optical power to an electric potential is of general interest
      for energy applications and is typically obtained via optical excitation of
      semiconductor materials. We developed a method for achieving electric potential
      that uses an all-metal geometry based on the plasmon resonance in metal
      nanostructures. In arrays of gold nanoparticles on an indium tin oxide substrate
      and arrays of 100-nanometer-diameter holes in 20-nanometer-thick gold films on a
      glass substrate, we detected negative and positive surface potentials during
      monochromatic irradiation at wavelengths below or above the plasmon resonance,
      respectively. We observed plasmoelectric surface potentials as large as 100
      millivolts under illumination of 100 milliwatts per square centimeter.
      Plasmoelectric devices may enable the development of all-metal optoelectronic
      devices that can convert light into electrical energy. 

PMID- 25395533
TI  - Strong bases. Directed ortho-meta'- and meta-meta'-dimetalations: a template base
      approach to deprotonation.
AB  - The regioselectivity of deprotonation reactions between arene substrates and
      basic metalating agents is usually governed by the electronic and/or coordinative
      characteristics of a directing group attached to the benzene ring. Generally, the
      reaction takes place in the ortho position, adjacent to the substituent. Here, we
      introduce a protocol by which the metalating agent, a disodium-monomagnesium
      alkyl-amide, forms a template that extends regioselectivity to more distant arene
      sites. Depending on the nature of the directing group, ortho-meta' or meta-meta'
      dimetalation is observed, in the latter case breaking the dogma of ortho
      metalation. This concept is elaborated through the characterization of both
      organometallic intermediates and electrophilically quenched products. 

PMID- 25395534
TI  - Sexual conflict. The evolution of infanticide by males in mammalian societies.
AB  - Male mammals often kill conspecific offspring. The benefits of such infanticide
      to males, and its costs to females, probably vary across mammalian social and
      mating systems. We used comparative analyses to show that infanticide primarily
      evolves in social mammals in which reproduction is monopolized by a minority of
      males. It has not promoted social counterstrategies such as female
      gregariousness, pair living, or changes in group size and sex ratio, but is
      successfully prevented by female sexual promiscuity, a paternity dilution
      strategy. These findings indicate that infanticide is a consequence, rather than
      a cause, of contrasts in mammalian social systems affecting the intensity of
      sexual conflict. 

PMID- 25395535
TI  - Landscape hydrology. The hydrological legacy of deforestation on global wetlands.
AB  - Increased catchment erosion and nutrient loading are commonly recognized impacts
      of deforestation on global wetlands. In contrast, an increase in water
      availability in deforested catchments is well known in modern studies but is
      rarely considered when evaluating past human impacts. We used a Budyko water
      balance approach, a meta-analysis of global wetland response to deforestation,
      and paleoecological studies from Australasia to explore this issue. After
      complete deforestation, we demonstrated that water available to wetlands
      increases by up to 15% of annual precipitation. This can convert ephemeral swamps
      to permanent lakes or even create new wetlands. This effect is globally
      significant, with 9 to 12% of wetlands affected, including 20 to 40% of Ramsar
      wetlands, but is widely unrecognized because human impact studies rarely test for
      it. 

PMID- 25395536
TI  - Climate change. Projected increase in lightning strikes in the United States due
      to global warming.
AB  - Lightning plays an important role in atmospheric chemistry and in the initiation
      of wildfires, but the impact of global warming on lightning rates is poorly
      constrained. Here we propose that the lightning flash rate is proportional to the
      convective available potential energy (CAPE) times the precipitation rate. Using
      observations, the product of CAPE and precipitation explains 77% of the variance
      in the time series of total cloud-to-ground lightning flashes over the contiguous
      United States (CONUS). Storms convert CAPE times precipitated water mass to
      discharged lightning energy with an efficiency of 1%. When this proxy is applied
      to 11 climate models, CONUS lightning strikes are predicted to increase 12 +/- 5%
      per degree Celsius of global warming and about 50% over this century. 

PMID- 25395537
TI  - Circadian rhythm. Dysrhythmia in the suprachiasmatic nucleus inhibits memory
      processing.
AB  - Chronic circadian dysfunction impairs declarative memory in humans but has little
      effect in common rodent models of arrhythmia caused by clock gene knockouts or
      surgical ablation of the suprachiasmatic nucleus (SCN). An important problem
      overlooked in these translational models is that human dysrhythmia occurs while
      SCN circuitry is genetically and neurologically intact. Siberian hamsters
      (Phodopus sungorus) are particularly well suited for translational studies
      because they can be made arrhythmic by a one-time photic treatment that severely
      impairs spatial and recognition memory. We found that once animals are made
      arrhythmic, subsequent SCN ablation completely rescues memory processing. These
      data suggest that the inhibitory effects of a malfunctioning SCN on cognition
      require preservation of circuitry between the SCN and downstream targets that are
      lost when these connections are severed. 

PMID- 25395538
TI  - A molecular ruler determines the repeat length in eukaryotic cilia and flagella.
AB  - Existence of cellular structures with specific size raises a fundamental question
      in biology: How do cells measure length? One conceptual answer to this question
      is by a molecular ruler, but examples of such rulers in eukaryotes are lacking.
      In this work, we identified a molecular ruler in eukaryotic cilia and flagella.
      Using cryo-electron tomography, we found that FAP59 and FAP172 form a 96
      nanometer (nm)-long complex in Chlamydomonas flagella and that the absence of the
      complex disrupted 96-nm repeats of axonemes. Furthermore, lengthening of the
      FAP59/172 complex by domain duplication resulted in extension of the repeats up
      to 128 nm, as well as duplication of specific axonemal components. Thus, the
      FAP59/172 complex is the molecular ruler that determines the 96-nm repeat length
      and arrangements of components in cilia and flagella. 

PMID- 25395540
TI  - The point of it all.

PMID- 25395539
TI  - Viral infection. Prevention and cure of rotavirus infection via TLR5/NLRC4
      mediated production of IL-22 and IL-18.
AB  - Activators of innate immunity may have the potential to combat a broad range of
      infectious agents. We report that treatment with bacterial flagellin prevented
      rotavirus (RV) infection in mice and cured chronically RV-infected mice.
      Protection was independent of adaptive immunity and interferon (IFN, type I and
      II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like
      receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells
      elicited production of the cytokine interleukin-22 (IL-22), which induced a
      protective gene expression program in intestinal epithelial cells. Flagellin also
      induced NLRC4-dependent production of IL-18 and immediate elimination of RV
      infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the
      capacity of flagellin to prevent or eliminate RV infection and thus holds promise
      as a broad-spectrum antiviral agent. 

PMID- 25395541
TI  - Synthetic biology. Genomically encoded analog memory with precise in vivo DNA
      writing in living cell populations.
AB  - Cellular memory is crucial to many natural biological processes and sophisticated
      synthetic biology applications. Existing cellular memories rely on epigenetic
      switches or recombinases, which are limited in scalability and recording
      capacity. In this work, we use the DNA of living cell populations as genomic
      "tape recorders" for the analog and distributed recording of long-term event
      histories. We describe a platform for generating single-stranded DNA (ssDNA) in
      vivo in response to arbitrary transcriptional signals. When coexpressed with a
      recombinase, these intracellularly expressed ssDNAs target specific genomic DNA
      addresses, resulting in precise mutations that accumulate in cell populations as
      a function of the magnitude and duration of the inputs. This platform could
      enable long-term cellular recorders for environmental and biomedical
      applications, biological state machines, and enhanced genome engineering
      strategies. 

PMID- 25395542
TI  - DNA recombination. Recombination initiation maps of individual human genomes.
AB  - DNA double-strand breaks (DSBs) are introduced in meiosis to initiate
      recombination and generate crossovers, the reciprocal exchanges of genetic
      material between parental chromosomes. Here, we present high-resolution maps of
      meiotic DSBs in individual human genomes. Comparing DSB maps between individuals
      shows that along with DNA binding by PRDM9, additional factors may dictate the
      efficiency of DSB formation. We find evidence for both GC-biased gene conversion
      and mutagenesis around meiotic DSB hotspots, while frequent colocalization of DSB
      hotspots with chromosome rearrangement breakpoints implicates the aberrant repair
      of meiotic DSBs in genomic disorders. Furthermore, our data indicate that DSB
      frequency is a major determinant of crossover rate. These maps provide new
      insights into the regulation of meiotic recombination and the impact of meiotic
      recombination on genome function. 

PMID- 25395543
TI  - Mesenchymal cells. Defining a mesenchymal progenitor niche at single-cell
      resolution.
AB  - Most vertebrate organs are composed of epithelium surrounded by support and
      stromal tissues formed from mesenchyme cells, which are not generally thought to
      form organized progenitor pools. Here, we use clonal cell labeling with
      multicolor reporters to characterize individual mesenchymal progenitors in the
      developing mouse lung. We observe a diversity of mesenchymal progenitor
      populations with different locations, movements, and lineage boundaries. Airway
      smooth muscle (ASM) progenitors map exclusively to mesenchyme ahead of budding
      airways. Progenitors recruited from these tip pools differentiate into ASM around
      airway stalks; flanking stalk mesenchyme can be induced to form an ASM niche by a
      lateral bud or by an airway tip plus focal Wnt signal. Thus, mesenchymal
      progenitors can be organized into localized and carefully controlled domains that
      rival epithelial progenitor niches in regulatory sophistication. 

PMID- 25395544
TI  - Association of the transcobalamin II gene 776C -> G polymorphism with Alzheimer's
      type dementia: dependence on the 5, 10-methylenetetrahydrofolate reductase 1298A 
      > C polymorphism genotype.
AB  - BACKGROUND: Decreased serum concentrations of vitamin B12 are associated with
      Alzheimer's type dementia. The transcobalamin II gene (TCN2) 776C -> G
      polymorphism affects transcobalamin II function as a carrier of vitamin B12 and
      might modify its availability. The association of the TCN2 776C -> G polymorphism
      with Alzheimer's type dementia is unclear and was investigated in the present
      study. METHODS: Case-control study including 27 individuals diagnosed with
      Alzheimer's type dementia and 28 healthy controls. Serum concentrations of
      vitamin B12, homocysteine and other analytes were determined and the presence of
      TCN2 776C -> G and 5, 10-methylenetetrahydrofolate reductase 1298A -> C
      polymorphisms genotypes was ascertained by polymerase chain reaction-restriction
      fragment length polymorphism. RESULTS: Serum concentrations of vitamin B12 were
      lower while those of homocysteine were higher in patients than in controls (P <
      0.05). The frequency of individuals carrying at least one 5, 10
      methylenetetrahydrofolate reductase 1298C allele was higher (59% versus 32%)
      while frequency of individuals harbouring at least one TCN2 776G allele was lower
      (58% versus 86%) in patients than in controls (P < 0.05). Univariate logistic
      regression showed negative association of TCN2 776CG genotype with Alzheimer's
      type dementia (OR = 0.17 versus CC genotype, P < 0.02). Multivariate logistic
      regression identified TCN2 776C -> G polymorphism as independent predictor of
      Alzheimer's type dementia together with higher concentrations of homocysteine,
      cholesterol and uric acid and lower concentrations of oestradiol. Association of
      TCN2 776C -> G polymorphism with Alzheimer's type dementia was observed for
      individuals carrying the 5,10-methylenetetrahydrofolate reductase 1298AA genotype
      but not the AC or CC genotypes, indicating interaction between the two
      polymorphisms. CONCLUSIONS: The TCN2 776C -> G polymorphism is negatively
      associated with Alzheimer's type dementia, suggesting a protective role against
      the disease in subjects with the 5, 10-methylenetetrahydrofolate reductase 1298AA
      genotype.

PMID- 25395545
TI  - Twin study implicates genetic factors in dry eye disease.

PMID- 25395546
TI  - The Scandinavian paradox revisited: Editorial comment on Berg-Hansen et al. 'High
      prevalence and no latitude gradient of multiple sclerosis in Norway'.

PMID- 25395547
TI  - Spinal cord MRI should always be performed in clinically isolated syndrome
      patients: No.

PMID- 25395548
TI  - Spinal cord MRI should always be performed in clinically isolated syndrome
      patients: Yes.

PMID- 25395549
TI  - Comparison of an ST80 MRSA strain from the USA with European ST80 strains.
AB  - OBJECTIVES: A number of community-acquired MRSA (CA-MRSA) clonal lineages
      dominate worldwide. ST80 was dominant in Europe and has increasingly been
      described from the Middle East. Here we report the whole genome sequence of the
      first ST80 CA-MRSA from the USA. METHODS: CA-MRSA isolate S0924 was obtained from
      a patient admitted to Cook County Hospital (Chicago, IL, USA) who came from
      Syria; the isolate belonged to spa type t044 and ST80. The whole genome sequence
      of S0924 was determined and compared with three previously published whole genome
      sequences of ST80 CA-MRSA from Europe and a newly sequenced ST80 CA-MRSA from the
      Netherlands (S1475). RESULTS: Based on spa typing, SCCmec type and virulence gene
      profile, this US ST80 isolate is indistinguishable from the European CA-MRSA ST80
      clone. SNP analysis within the conserved core genome showed clear differences
      between the strains with up to 144 SNPs differing between S0924 and strain S1800,
      an ST80 MRSA from Greece. The gene content showed 21 regions of difference
      between the US and European isolates, although these were largely restricted to
      mobile genetic elements. Phylogenetic reconstruction indicated that the European
      strains were more closely related to each other than to the US strain. The SNP
      data suggest that a common ancestor existed around two decades ago, indicating
      that the US and European ST80 strains are clonally linked. CONCLUSIONS: These
      data combined with the country of origin of the patient suggest that ST80 S0924
      was probably relatively recently introduced into the USA from Syria.

PMID- 25395553
TI  - Prevalence and Description of Palliative Care in US Nursing Homes: A Descriptive
      Study.
AB  - OBJECTIVE: To describe rates and policies in U.S. Nursing Homes (NH) related to
      palliative care, comfort care, and hospice care based on a nationwide survey of
      directors of nursing. MEASUREMENTS: A national survey was distributed online and
      was completed by 316 directors of nursing of NHs (11% response rate). The
      directors of nursing were asked about availability and policies in their
      facilities. Specifically, questions were related to policies, referral patterns,
      discussion about such care, and types of medical conditions qualifying for such
      services. RESULTS: Hospice is significantly more available than palliative or
      comfort care programs; also, for-profit facilities, compared to non-profits, are
      significantly more likely to have palliative care programs and medical directors
      for palliative care. Social workers and nurses were most likely to suggest
      palliative type programs. Only 42% of facilities with palliative program provide
      consultation by a palliative certified physician. Residents with non-healing
      pressure ulcers, frequent hospitalizations, or severe/uncontrolled pain or non
      pain symptoms were less likely to be referred. CONCLUSIONS: There is limited
      availability of palliative type programs in NH facilities and underutilization in
      those NH with programs.

PMID- 25395554
TI  - Bovine TB: Changes to delivery of TB testing set for April 2015.

PMID- 25395555
TI  - Welfare at slaughter: FSA to record all breaches of stunning rules at slaughter.

PMID- 25395556
TI  - Notifiable diseases: Contagious agalactia pathogen confirmed in Wales.

PMID- 25395557
TI  - Grants available: Gates Foundation seeks innovative concepts for animal vaccines.

PMID- 25395558
TI  - Research: Collaborating on livestock health and wellbeing.

PMID- 25395561
TI  - Public health: Health professionals in Europe urged to be prepared for Ebola
      virus.

PMID- 25395562
TI  - Appeals: VPHA appeals for funds to help rebuild lives following European floods.

PMID- 25395563
TI  - One Health: Antimicrobial resistance and disease control: making One Health work.
AB  - Antimicrobial resistance and infectious disease control were the main themes at a
      One Health conference held in London last month. Hosted collaboratively by the
      Royal Society of Medicine and the Bella Moss Foundation, the meeting put
      particular emphasis on making the One Health concept work when dealing with
      resistance and disease control. Georgina Mills reports.

PMID- 25395564
TI  - BCVA: Can recycled manure make a safe bed for cattle?
AB  - The use of recycled manure solids for cattle bedding was among the subjects
      considered at the British Cattle Veterinary Association's congress last month.
      Both cattle and sheep vets gathered in Hinckley, Leicestershire, from October 16
      to 18 to discuss a range of clinical and political issues. Suzanne Jarvis
      reports. 

PMID- 25395565
TI  - FSA reiterates its advice on raw milk.

PMID- 25395566
TI  - SAC C VS disease surveillance report: Border disease outbreak leads to ongoing
      sheep losses.

PMID- 25395567
TI  - A model for the control of psoroptic mange in sheep.

PMID- 25395568
TI  - Postmortem services: Provision of diagnostic postmortem examination services.

PMID- 25395569
TI  - One Health: The complex issue of dog bites.

PMID- 25395570
TI  - Specialisation: British college of veterinary specialists.

PMID- 25395571
TI  - More than a seven-year itch.
AB  - Keith Thoday's career in dermatology came about almost by accident and, he says,
      has often been helped by being in the right place at the right time. 

PMID- 25395572
TI  - Predicting depression and quality of life among long-term head and neck cancer
      survivors.
AB  - OBJECTIVE: The aim of this study is to identify clinical factors that are
      predictive of depression and quality of life (QOL) among long-term survivors of
      head and neck squamous cell carcinoma and to develop predictive scores using
      these factors. STUDY DESIGN: Cohort study SETTING: Tertiary referral center.
      SUBJECTS AND METHODS: A total of 209 posttreatment (median follow-up, 38.7
      months) head and neck cancer patients were prospectively evaluated using the
      Hospital Anxiety Depression Scale (HADS), the European Organization for Research
      and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, and the
      EORTC Quality of Life Questionnaire Head and Neck 35, and pretreatment patient
      related, tumor-related, and treatment-related predictors were identified using
      chart review. Bivariate (chi(2) and t test) and multivariate (linear regression)
      analyses were used to construct predictive models. RESULTS: Significant
      pretreatment predictors of depression were identified on multivariate analysis as
      smoking at diagnosis, >14 alcoholic drinks per week, T3 or T4 status, and >3
      medications (P < .001). Two or more of these factors yielded an 82.3% sensitivity
      in detecting significant depressive symptoms (defined as a HADS cutoff score of
      5). Significant predictors of fatigue, global health/QOL, social contact, speech,
      pain, swallowing, and xerostomia were also identified. CONCLUSION: Pretreatment
      predictors of long-term depression and QOL have been defined using multivariate
      models, and an easily applicable predictive score of long-term depression is
      proposed. Potential eventual clinical applications include prophylactic
      intervention in at-risk patients.

PMID- 25395573
TI  - Serial imaging observations of vascular healing in a denervation-induced renal
      artery dissection.

PMID- 25395574
TI  - Making the Case for History in Medical Education.
AB  - Historians of medicine have struggled for centuries to make the case for history
      in medical education. They have developed many arguments about the value of
      historical perspective, but their efforts have faced persistent obstacles, from
      limited resources to curricular time constraints and skepticism about whether
      history actually is essential for physicians. Recent proposals have suggested
      that history should ally itself with the other medical humanities and make the
      case that together they can foster medical professionalism. We articulate a
      different approach and make the case for history as an essential component of
      medical knowledge, reasoning, and practice. History offers essential insights
      about the causes of disease (e.g., the non-reductionistic mechanisms needed to
      account for changes in the burden of disease over time), the nature of efficacy
      (e.g., why doctors think that their treatments work, and how have their
      assessments changed over time), and the contingency of medical knowledge and
      practice amid the social, economic, and political contexts of medicine. These are
      all things that physicians must know in order to be effective diagnosticians and
      caregivers, just as they must learn anatomy or pathophysiology. The specific
      arguments we make can be fit, as needed, into the prevailing language of
      competencies in medical education. 

PMID- 25395575
TI  - Transnasal endoscopic treatment of orbital complications of acute sinusitis: the
      Graz concept.
AB  - OBJECTIVE: Orbital complications of acute sinusitis can be severe. Nowadays,
      surgical drainage of intraorbital abscess formations is performed endoscopically
      in the majority of cases. This study aims to illustrate the Graz experience in
      the endoscopic treatment of orbital complications and to present our treatment
      algorithm. METHODS: In a retrospective study, 53 patients were examined who were
      referred to the Department of General Otorhinolaryngology of the ENT-University
      Hospital Graz from 2000 to 2011. RESULTS: Of 53 patients, men were affected more
      frequently than women (n=37, 69.81% vs n=16, 30.19%). The following diagnoses
      were obtained: 9 preseptal cellulitis, 7 orbital cellulitis, 14 subperiosteal
      abscesses, and 23 orbital abscesses. In 16 patients, a conservative therapy was
      administered; 37 patients underwent surgery, most of them purely endoscopically
      (n=31, 83.78%). Two of the patients who underwent conservative treatment and 7 of
      those who underwent surgery experienced a recurrence (n=9, 16.98%). CONCLUSION:
      Based on analysis of our recurrences, we have tried to create the optimal
      treatment algorithm as a point of reference in the management of orbital
      complications of acute sinusitis. In this way, 7 of 9 recurrences could have been
      avoided, equaling a hypothetical recurrence rate of 3.77% instead of 16.98%
      (hypothetical success rate 96.23%).

PMID- 25395576
TI  - Development and Validation of the Temperament and Affectivity Inventory (TAI).
AB  - Trait affect scales have been a mainstay of the assessment literature for more
      than 50 years. These scales have demonstrated impressive construct validity,
      including substantial relations with personality, satisfaction, and
      psychopathology. However, the accumulating evidence has exposed several
      limitations, including (a) problems associated with retrospective biases, (b)
      lower temporal stability because of enhanced susceptibility to transient error,
      and (c) reduced self-other agreement. These limitations motivated the creation of
      the Temperament and Affectivity Inventory (TAI), which uses a traditional
      personality format (i.e., full sentences rather than single words or short
      phrases). The 12 TAI scales were created based on factor analyses in two samples
      and validated in four additional samples. The scales are internally consistent,
      highly stable over time, and show strong convergent, discriminant, and
      incremental validity in relation to self-report and interview-based measures of
      personality and psychopathology. Thus, the TAI provides a promising new approach
      to assessing trait affectivity. 

PMID- 25395577
TI  - Promoting palliative care in the community: production of the primary palliative
      care toolkit by the European Association of Palliative Care Taskforce in primary
      palliative care.
AB  - BACKGROUND: A multidisciplinary European Association of Palliative Care Taskforce
      was established to scope the extent of and learn what facilitates and hinders the
      development of palliative care in the community across Europe. AIM: To document
      the barriers and facilitators for palliative care in the community and to produce
      a resource toolkit that palliative care specialists, primary care health
      professionals or policymakers, service developers, educationalists and national
      groups more generally could use to facilitate the development of palliative care
      in their own country. DESIGN: (1) A survey instrument was sent to general
      practitioners with knowledge of palliative care services in the community in a
      diverse sample of European countries. We also conducted an international
      systematic review of tools used to identify people for palliative care in the
      community. (2) A draft toolkit was then constructed suggesting how individual
      countries might best address these issues, and an online survey was then set up
      for general practitioners and specialists to make comments. Iterations of the
      toolkit were then presented at international palliative care and primary care
      conferences. RESULTS: Being unable to identify appropriate patients for
      palliative care in the community was a major barrier internationally. The
      systematic review identified tools that might be used to help address this.
      Various facilitators such as national strategies were identified. A primary
      palliative care toolkit has been produced and refined, together with associated
      guidance. CONCLUSION: Many barriers and facilitators were identified. The primary
      palliative care toolkit can help community-based palliative care services to be
      established nationally.

PMID- 25395578
TI  - Hospital-based bereavement services following the death of a child: a mixed study
      review.
AB  - BACKGROUND: There has been a breadth of research on the grief experience of
      parents following the death of a child. However, the role and impact of hospital
      based bereaved services remain unclear. AIM: To identify services offered to
      bereaved families in perinatal, neonatal, and pediatric hospital settings and
      summarize the psychosocial impact of these services and published recommendations
      for best practice hospital-based bereavement care. DESIGN: Systematic review of
      qualitative, quantitative, and mixed method studies guided by the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses checklist and
      methodological quality appraised in accordance with the Mixed Method Appraisal
      Tool. DATA SOURCES: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied
      Health, and PsychINFO were searched to find studies describing hospital-based
      bereavement services/interventions for parents, siblings, and grandparents.
      RESULTS: In all, 14 qualitative, 6 quantitative, and 10 mixed method studies were
      identified. Nine descriptive articles were also included. Qualitatively, family
      members described feeling cared for and supported by staff, a reduction in sense
      of isolation, and improved coping and personal growth. Quantitatively,
      bereavement services have most effect for parents experiencing more complex
      mourning. It is recommended that bereavement services be theoretically driven and
      evidence based, offer continuity of care prior to and following the death of a
      child, and provide a range of interventions for the "whole family" and
      flexibility in service delivery. CONCLUSIONS: There is a role for transitional
      hospital-based services/interventions for families in the lead up to and
      following the death of a child. Further mixed method research is required to
      inform best practice bereavement care guidelines in the perinatal, neonatal, and
      pediatric hospital settings.

PMID- 25395579
TI  - Chromosome congression is promoted by CENP-Q- and CENP-E-dependent pathways.
AB  - A key step of mitosis is the congression of chromosomes to the spindle equator.
      Congression is driven by at least two distinct mechanisms: (1) kinetochores slide
      along the microtubule lattice using the plus-end directed CENP-E motor, and (2)
      kinetochores biorientating near the pole move to the equator through microtubule
      depolymerisation-coupled pulling. Here, we show that CENP-Q - a subunit of the
      CENP-O complex (comprising CENP-O, CENP-P, CENP-Q and CENP-U) that targets polo
      like kinase (Plk1) to kinetochores - is also required for the recruitment of CENP
      E to kinetochores. We further reveal a CENP-E recruitment-independent role for
      CENP-Q in depolymerisation-coupled pulling. Both of these functions are abolished
      by a single point mutation in CENP-Q (S50A) - a residue that is phosphorylated in
      vivo. Importantly, the S50A mutant does not affect the loading of Plk1 onto
      kinetochores and leaves the CENP-O complex intact. Thus, the functions of CENP-Q
      in CENP-E loading and depolymerisation-coupled pulling are independent from its
      role in Plk1 recruitment and CENP-O complex stabilisation. Taken together, our
      data provide evidence that phosphoregulation of CENP-Q plays a central function
      in coordinating chromosome congression mechanisms.

PMID- 25395580
TI  - INPP5E interacts with AURKA, linking phosphoinositide signaling to primary cilium
      stability.
AB  - Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause the
      ciliopathies known as Joubert and MORM syndromes; however, the role of INPP5E in
      ciliary biology is not well understood. Here, we describe an interaction between
      INPP5E and AURKA, a centrosomal kinase that regulates mitosis and ciliary
      disassembly, and we show that this interaction is important for the stability of
      primary cilia. Furthermore, AURKA phosphorylates INPP5E and thereby increases its
      5-phosphatase activity, which in turn promotes transcriptional downregulation of
      AURKA, partly through an AKT-dependent mechanism. These findings establish the
      first direct link between AURKA and phosphoinositide signaling and suggest that
      the function of INPP5E in cilia is at least partly mediated by its interactions
      with AURKA. 

PMID- 25395581
TI  - Shear-sensitive microRNA-34a modulates flow-dependent regulation of endothelial
      inflammation.
AB  - Although many studies have described the roles of microRNAs (miRNAs) in the
      modulation of the endothelial response to shear stress, the mechanisms remain
      incompletely understood. Here, we demonstrate that miR-34a expression in
      endothelial cells was downregulated by atheroprotective physiological high shear
      stress (HSS), whereas it was upregulated by atheroprone oscillatory shear stress
      (OSS). Blockade of endogenous miR-34a dramatically decreased basal vascular cell
      adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1)
      protein expression levels. Conversely, miR-34a overexpression increased the
      protein levels of VCAM-1 and ICAM-1, consequently promoting monocyte adhesion to
      endothelial cells. Furthermore, miR-34a overexpression attenuated HSS-mediated
      suppression of VCAM-1 protein expression on endothelial cells, but promoted HSS
      induced ICAM-1 expression. In addition, the OSS induction of endothelial cell
      VCAM-1 and ICAM-1 was suppressed by using an miR-34a inhibitor, which led to a
      reduction of monocyte adhesion to endothelial cells. Mechanistically, sirtuin 1
      overexpression partially prevented miR-34a-induced VCAM-1 and ICAM-1 expression.
      Subsequent investigation demonstrated that miR-34a increased nuclear factor
      kappaB (NF-kappaB) p65 subunit (also known as RelA) acetylation (on residue
      Lys310), and silencing NF-kappaB signaling reduced miR-34a-induced VCAM-1 and
      ICAM-1 protein expression. These results demonstrate that miR-34a is involved in
      the flow-dependent regulation of endothelial inflammation.

PMID- 25395582
TI  - Cadherin controls nectin recruitment into adherens junctions by remodeling the
      actin cytoskeleton.
AB  - The mechanism that coordinates activities of different adhesion receptors is
      poorly understood. We investigated this mechanism by focusing on the nectin-2 and
      E-cadherin adherens junction receptors. We found that, cadherin was not required
      for the basic process of nectin junction formation because nectin-2 formed
      junctions in cadherin-deficient A431D cells. Formation of nectin-2 junctions in
      these cells, however, became regulated by cadherin as soon as E-cadherin was re
      expressed. E-cadherin recruited nectin-2 into adherens junctions, where both
      proteins formed distinct but tightly associated clusters. Live-cell imaging
      showed that the appearance of E-cadherin clusters often preceded that of nectin-2
      clusters at sites of junction assembly. Inactivation of E-cadherin clustering by
      different strategies concomitantly suppressed the formation of nectin clusters.
      Furthermore, cadherin significantly increased the stability of nectin clusters,
      thereby making them resistant to the BC-12 antibody, which targets the nectin-2
      adhesion interface. By testing different E-cadherin-alpha-catenin chimeras, we
      showed that the recruitment of nectin into chimera junctions is mediated by the
      actin-binding domain of alpha-catenin. Our data suggests that E-cadherin
      regulates assembly of nectin junctions through alpha-catenin-induced remodeling
      of the actin cytoskeleton around the cadherin clusters. 

PMID- 25395583
TI  - Actin-capping proteins play essential roles in the asymmetric division of
      maturing mouse oocytes.
AB  - Actin polymerization is essential for various stages of mammalian oocyte
      maturation, including spindle migration, actin cap formation, polar body
      extrusion and cytokinesis. The heterodimeric actin-capping protein is an
      essential element of the actin cytoskeleton. It binds to the fast-growing
      (barbed) ends of actin filaments and plays essential roles in various actin
      mediated cellular processes. However, the roles of capping protein in mammalian
      oocyte maturation are poorly understood. We investigated the roles of capping
      protein in mouse oocytes and found that it is essential for correct asymmetric
      spindle migration and polar body extrusion. Capping protein mainly localized in
      the cytoplasm during maturation. By knocking down or ectopically overexpressing
      this protein, we revealed that it is crucial for efficient spindle migration and
      maintenance of the cytoplasmic actin mesh density. Expression of the capping
      protein-binding region of CARMIL (also known as LRRC16A) impaired spindle
      migration and polar body extrusion during oocyte maturation and decreased the
      density of the cytoplasmic actin mesh. Taken together, these findings show that
      capping protein is an essential component of the actin cytoskeleton machinery
      that plays crucial roles in oocyte maturation, presumably by controlling the
      cytoplasmic actin mesh density. 

PMID- 25395585
TI  - Early diagnosis of Duchenne muscular dystrophy is essential to improve long term
      outcomes.

PMID- 25395584
TI  - BRG1 promotes the repair of DNA double-strand breaks by facilitating the
      replacement of RPA with RAD51.
AB  - DNA double-strand breaks (DSBs) are a type of lethal DNA damage. The repair of
      DSBs requires tight coordination between the factors modulating chromatin
      structure and the DNA repair machinery. BRG1, the ATPase subunit of the chromatin
      remodelling complex Switch/Sucrose non-fermentable (SWI/SNF), is often linked to
      tumorigenesis and genome instability, and its role in DSB repair remains largely
      unclear. In the present study, we show that BRG1 is recruited to DSB sites and
      enhances DSB repair. Using DR-GFP and EJ5-GFP reporter systems, we demonstrate
      that BRG1 facilitates homologous recombination repair rather than nonhomologous
      end-joining (NHEJ) repair. Moreover, the BRG1-RAD52 complex mediates the
      replacement of RPA with RAD51 on single-stranded DNA (ssDNA) to initiate DNA
      strand invasion. Loss of BRG1 results in a failure of RAD51 loading onto ssDNA,
      abnormal homologous recombination repair and enhanced DSB-induced lethality. Our
      present study provides a mechanistic insight into how BRG1, which is known to be
      involved in chromatin remodelling, plays a substantial role in the homologous
      recombination repair pathway in mammalian cells. 

PMID- 25395586
TI  - Toxic shock syndrome: under-recognised and under-treated?

PMID- 25395588
TI  - Towards evidence based medicine for paediatricians.

PMID- 25395591
TI  - Modification of a salmonid alphavirus replicon vector for enhanced expression of
      heterologous antigens.
AB  - A salmonid alphavirus (SAV) replicon has been developed to express heterologous
      antigens but protein production was low to modest compared with terrestrial
      alphavirus replicons. In this study, we have compared several modifications to a
      SAV replicon construct and analysed their influence on foreign gene expression.
      We found that an insertion of a translational enhancer consisting of the N
      terminal 102 nt of the capsid gene, together with a nucleotide sequence encoding
      the foot-and-mouth disease virus (FMDV) 2A peptide, caused a significant increase
      in EGFP reporter gene expression. The importance of fusing a hammerhead (HH)
      ribozyme sequence at the 5' end of the viral genome was also demonstrated. In
      contrast, a hepatitis D virus ribozyme (HDV-RZ) sequence placed at the 3' end did
      not augment expression of inserted genes. Taken together, we have developed a
      platform for optimized antigen production, which can be applied for immunization
      of salmonid fish in the future. 

PMID- 25395590
TI  - A novel apolipoprotein C-II mimetic peptide that activates lipoprotein lipase and
      decreases serum triglycerides in apolipoprotein E-knockout mice.
AB  - Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as
      possible new agents for the treatment of cardiovascular disease based on their
      ability to promote cholesterol efflux and their other beneficial antiatherogenic
      properties. Many of these peptides, however, have been reported to cause
      transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein
      lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that
      contains an amphipathic helix (18A) for binding to lipoproteins and stimulating
      cholesterol efflux as well as a motif based on the last helix of apolipoprotein C
      II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted
      cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK
      cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to
      be comparable to the full-length apoC-II protein in activating lipolysis by LPL.
      When added to serum from a patient with apoC-II deficiency, it restored normal
      levels of LPL-induced lipolysis and also enhanced lipolysis in serum from
      patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a
      (30 mg/kg) in apolipoprotein E-knockout mice resulted in a significant reduction
      of plasma cholesterol and triglycerides of 38 +/- 6% and 85 +/- 7%, respectively,
      at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg)
      peptide was found to completely block the hypertriglyceridemic effect of the 5A
      peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II,
      which promotes cholesterol efflux and lipolysis and may therefore be useful for
      the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. 

PMID- 25395592
TI  - Chikungunya virus non-structural protein 2-mediated host shut-off disables the
      unfolded protein response.
AB  - The unfolded protein response (UPR) is a cellular defence mechanism against high
      concentrations of misfolded protein in the endoplasmic reticulum (ER). In the
      presence of misfolded proteins, ER-transmembrane proteins PERK and IRE1alpha
      become activated. PERK phosphorylates eIF2alpha leading to a general inhibition
      of cellular translation, whilst the expression of transcription factor ATF4 is
      upregulated. Active IRE1alpha splices out an intron from XBP1 mRNA, to produce a
      potent transcription factor. Activation of the UPR increases the production of
      several proteins involved in protein folding, degradation and apoptosis. Here, we
      demonstrated that transient expression of chikungunya virus (CHIKV) (family
      Togaviridae, genus Alphavirus) envelope glycoproteins induced the UPR and that
      CHIKV infection resulted in the phosphorylation of eIF2alpha and partial splicing
      of XBP1 mRNA. However, infection with CHIKV did not increase the expression of
      ATF4 and known UPR target genes (GRP78/BiP, GRP94 and CHOP). Moreover, nuclear
      XBP1 was not observed during CHIKV infection. Even upon stimulation with
      tunicamycin, the UPR was efficiently inhibited in CHIKV-infected cells.
      Individual expression of CHIKV non-structural proteins (nsPs) revealed that nsP2
      alone was sufficient to inhibit the UPR. Mutations that rendered nsP2 unable to
      cause host-cell shut-off prevented nsP2-mediated inhibition of the UPR. This
      indicates that initial UPR induction takes place in the ER but that expression of
      functional UPR transcription factors and target genes is efficiently inhibited by
      CHIKV nsP2. 

PMID- 25395593
TI  - A soluble envelope protein of endogenous retrovirus (FeLIX) present in serum of
      domestic cats mediates infection of a pathogenic variant of feline leukemia
      virus.
AB  - T-lymphotropic feline leukemia virus (FeLV-T), a highly pathogenic variant of
      FeLV, induces severe immunosuppression in cats. FeLV-T is fusion defective
      because in its PHQ motif, a gammaretroviral consensus motif in the N terminus of
      an envelope protein, histidine is replaced with aspartate. Infection by FeLV-T
      requires FeLIX, a truncated envelope protein encoded by an endogenous FeLV, for
      transactivation of infectivity and Pit1 for binding FeLIX. Although Pit1 is
      present in most tissues in cats, the expression of FeLIX is limited to certain
      cells in lymphoid organs. Therefore, the host cell range of FeLV-T was thought to
      be restricted to cells expressing FeLIX. However, because FeLIX is a soluble
      factor and is expressed constitutively in lymphoid organs, we presumed it to be
      present in blood and evaluated its activities in sera of various mammalian
      species using a pseudotype assay. We demonstrated that cat serum has FeLIX
      activity at a functional level, suggesting that FeLIX is present in the blood and
      that FeLV-T may be able to infect cells expressing Pit1 regardless of the
      expression of FeLIX in vivo. In addition, FeLIX activities in sera were detected
      only in domestic cats and not in other feline species tested. To our knowledge,
      this is the first report to prove that a large amount of truncated envelope
      protein of endogenous retrovirus is circulating in the blood to facilitate the
      infection of a pathogenic exogenous retrovirus. 

PMID- 25395595
TI  - Genetic and antigenic structural characterization for resistance of echovirus 11
      to pleconaril in an immunocompromised patient.
AB  - Pleconaril is a capsid inhibitor used previously to treat enterovirus infections.
      A pleconaril-resistant echovirus 11 (E11) strain was identified before pleconaril
      treatment was given in an immunocompromised patient. The patient was also treated
      with intravenous Ig (IVIg) for a long period but remained unresponsive. The
      pleconaril-resistant strains could not be neutralized in vitro, confirming IVIg
      treatment failure. To identify the basis of pleconaril resistance, genetic and
      structural analyses were conducted. Analysis of a modelled viral capsid indicated
      conformational changes in the hydrophobic pocket that could prevent pleconaril
      docking. Substitutions (V117I, V119M and I188L) in the pleconaril-resistant
      viruses were found in the pocket region of VP1. Modelling suggested that V119M
      could confer resistance, most probably due to the protruding sulfate side chain
      of methionine. Although pleconaril resistance induced in vitro in a susceptible
      E11 clinical isolate was characterized by a different substitution (I183M),
      resistance was suggested to also result from a similar mechanism, i.e. due to a
      protruding sulfate side chain of methionine. Our results showed that resistant
      strains that arise in vivo display different markers from those identified in
      vitro and suggest that multiple factors may play a role in pleconaril resistance
      in patient strains. Based on IVIg treatment failure, we predict that one of these
      factors could be immune related. Thus, both IVIg and capsid inhibitors target the
      viral capsid and can induce mutations that can be cross-reactive, enabling escape
      from both IVIg and the drug. This could limit treatment options and should be
      investigated further. 

PMID- 25395594
TI  - An investigation of the breadth of neutralizing antibody response in cats
      naturally infected with feline immunodeficiency virus.
AB  - Neutralizing antibodies (NAbs) are believed to comprise an essential component of
      the protective immune response induced by vaccines against feline
      immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) infections.
      However, relatively little is known about the role of NAbs in controlling FIV
      infection and subsequent disease progression. Here, we present studies where we
      examined the neutralization of HIV-luciferase pseudotypes bearing homologous and
      heterologous FIV envelope proteins (n = 278) by sequential plasma samples
      collected at 6 month intervals from naturally infected cats (n = 38) over a
      period of 18 months. We evaluated the breadth of the NAb response against non
      recombinant homologous and heterologous clade A and clade B viral variants, as
      well as recombinants, and assessed the results, testing for evidence of an
      association between the potency of the NAb response and the duration of
      infection, CD4(+) T lymphocyte numbers, health status and survival times of the
      infected cats. Neutralization profiles varied significantly between FIV-infected
      cats and strong autologous neutralization, assessed using luciferase-based in
      vitro assays, did not correlate with the clinical outcome. No association was
      observed between strong NAb responses and either improved health status or
      increased survival time of infected animals, implying that other protective
      mechanisms were likely to be involved. Similarly, no correlation was observed
      between the development of autologous NAbs and the duration of infection.
      Furthermore, cross-neutralizing antibodies were evident in only a small
      proportion (13 %) of cats.

PMID- 25395596
TI  - Interinstitutional variations in mode of birth after a previous caesarean
      section: a cross-sectional study in six German hospitals.
AB  - AIMS: Regional and interinstitutional variations have been recognized in the
      increasing incidence of caesarean section. Modes of birth after previous
      caesarean section vary widely, ranging from elective repeat caesarean section
      (ERCS) and unplanned repeat caesarean section (URCS) after trial of labour to
      vaginal birth after caesarean section (VBAC). This study describes
      interinstitutional variations in mode of birth after previous caesarean section
      in relation to regional indicators in Germany. MATERIAL AND METHODS: A cross
      sectional study using the birth registers of six maternity units (n=12,060) in
      five different German states (n=370,209). Indicators were tested by chi2 and
      relative deviations from regional values were expressed as relative risks and 95%
      confidence intervals. RESULTS: The percentages of women in the six units with
      previous caesarean section ranged from 11.9% to 15.9% (P=0.002). VBAC was planned
      for 36.0% to 49.8% (P=0.003) of these women, but actually completed in only 26.2%
      to 32.8% (P=0.66). Depending on the indicator, the units studied deviated from
      the regional data by up to 32% [relative risk 0.68 (0.47-0.97)] in respect of
      completed VBAC among all initiated VBAC. CONCLUSIONS: There is substantial
      interinstitutional variation in mode of birth following previous caesarean
      section. This variation is in addition to regional patterns.

PMID- 25395597
TI  - Understanding health-care access and utilization disparities among Latino
      children in the United States.
AB  - It is important to understand the source of health-care disparities between
      Latinos and other children in the United States. We examine parent-reported
      health-care access and utilization among Latino, White, and Black children (<=17
      years old) in the United States in the 2006-2011 National Health Interview
      Survey. Using Blinder-Oaxaca decomposition, we portion health-care disparities
      into two parts (1) those attributable to differences in the levels of
      sociodemographic characteristics (e.g., income) and (2) those attributable to
      differences in group-specific regression coefficients that measure the health
      care 'return' Latino, White, and Black children receive on these characteristics.
      In the United States, Latino children are less likely than Whites to have a usual
      source of care, receive at least one preventive care visit, and visit a doctor,
      and are more likely to have delayed care. The return on sociodemographic
      characteristics explains 20-30% of the disparity between Latino and White
      children in the usual source of care, delayed care, and doctor visits and 40-50%
      of the disparity between Latinos and Blacks in emergency department use and
      preventive care. Much of the health-care disadvantage experienced by Latino
      children would persist if Latinos had the sociodemographic characteristics as
      Whites and Blacks.

PMID- 25395598
TI  - Improving and validating children's nurses communication skills with standardized
      patients in end of life care.
AB  - Children's nurse education is experiencing increases in recruitment targets at
      the same time that clinical placements are decreasing. With regard to end-of-life
      care, it is has become a challenge to ensure that all students come into contact
      with a satisfactory range of experience as part of the requirement for competency
      at the point of registration. The aim of our study was to find out if students at
      the end of their course were able to use communication skills acquired in their
      three years of training and adapt and transfer them to a specific palliative care
      context even if they had never worked in that area of care. Focus groups were
      conducted after the simulations which explored the students' experiences of being
      involved in the scenarios. Four themes emerged that students identified either
      inhibited or enabled their communication skills, which included anxiety and fear,
      the need for professional props, the experience of it being real and feeling
      empowered.

PMID- 25395599
TI  - Enhancement of cytotoxic effect on human head and neck cancer cells by
      combination of photodynamic therapy and sulforaphane.
AB  - Photodynamic therapy (PDT) is a method to treat cancers using photosensitizer and
      light. PDT has been tried for several tumors. However, the clinical applications
      are limited by the toxicity of photosensitizer and narrow effect. Sulforaphane
      (SFN) is a material of isothiocyanate group and known to have anticancer effect.
      We evaluated the cytotoxic effect of PDT combined with SFN on human head and neck
      cancer cells. We measured the cell viability, extent of apoptosis and necrosis,
      reactive oxygen species (ROS) generation and caspase activation. Cell viability
      was decreased significantly by combination treatment. Cellular apoptosis and
      necrosis were increased in combination treatment compared to SFN or PDT. ROS
      generation was also higher in combination treatment than single treatment. In
      combination treatment group, apoptosis and necrosis were decreased by
      administration of sodium azide (SA) which is scavenger of ROS. Increased caspase
      activation in combination treatment was also inhibited by SA. Combination of PDT
      and SFN led to enhanced cytotoxic effect on head and neck cancer cells.
      Combination treatment promoted the ROS generation, which induced cell death
      through activation of caspase pathway. 

PMID- 25395600
TI  - Vibroacustic microvibrations enhance kidney blood supply, glomerular filtration
      and glutathione peroxidase activity in spontaneously hypertensive rats.
AB  - Limited numbers of studies include research of microvibration therapy in
      experimental models. We examined effects of chronic vibroacustic-microvibration
      treatment on haemodynamics and anti-oxidative defense in experimental
      hypertension. Study was performed on chronically treated hypertensive and
      normotensive Wistar rats. Mean arterial pressure (MAP), cardiac output (CO),
      renal blood flow (RBF), glomerular filtration and activity of anti-oxidative
      enzymes were determined after three weeks treatment. Vibroacustic treatment had
      no influence on MAP and CO, but RBF was increased in both groups of treated rats.
      Additionally, vibroacustic treatment enhanced diuresis and increased glomerular
      filtration in hypertensive rats. Glutathione peroxidase (GSH-Px) activity was
      elevated in both treated rat strains, but activity of superoxide dismutase was
      unchanged. We conclude that microvibration treatment doesn't ameliorate
      hypertension but improves renal blood supply (trough diminished renal vascular
      resistance), glomerular filtration, diuresis, and enhances glutathione dependent
      anti-oxidant defense with more important beneficials in hypertensive animals. 

PMID- 25395601
TI  - Intestinal ischemia-reperfusion injury mediates expression of inflammatory
      cytokines in rats.
AB  - The small intestine is an organ with very well developed immunological activity,
      responsible for synthesis of specific inflammatory mediators that participate in
      causing the systemic inflammation that can occur after ischemia-reperfusion
      injury. The aim of our work was to study mRNA expression and protein
      concentration of inflammatory cytokines IL-10 and TNFalpha in the jejunal wall
      after intestinal ischemia-reperfusion injury (IRI). Cytokine concentration levels
      confirmed the direct effect of IRI on the inflammation process. The results refer
      to the changes in balance between pro-inflammatory and anti-inflammatory
      mediators and indicate that the predominant disturbance of homeostasis after
      intestinal IRI is present after 1 hour of reperfusion. 

PMID- 25395602
TI  - Does static magnetic field-exposure induced oxidative stress and apoptosis in rat
      kidney and muscle? Effect of vitamin E and selenium supplementations.
AB  - Static magnetic fields (SMFs) effect observed with radical pair recombination is
      one of the well-known mechanisms by which SMFs interact with biological systems.
      Our aim was to study whether SMF induces oxidative stress and apoptosis in rat
      tissues and to evaluate the possible protector effect of selenium (Se) and
      vitamin E (vit E) supplementations. Rats were randomly divided into control, SMF
      exposed, Se-treated, vit E-treated, SMF exposed rats and co-treated with Se, and
      SMF exposed rats and co-treated with vit E. After animal sacrifice, catalase
      (CAT) activity and malondialdehyde (MDA) concentration were measured and
      apoptosis inducing factor (AIF) immunohistochemical labeling was performed in
      kidney and muscle. Exposure of rats to SMF (128 mT, 1 h/day for 5 days) increased
      the MDA concentrations (+25%) and CAT activities (+34%) in kidney but not in
      muscle. By contrast, the same treatment failed to induce a caspase-independent
      pathway apoptosis in both tissues. Interestingly, Se pre-treatment inhibited the
      increase of MDA concentrations and CAT activities in kidney in SMF-exposed rats.
      However, vit E administration corrected only MDA levels in rat kidney. In
      conclusion, exposure to SMF induced oxidative stress in kidney that can be
      prevented by treatment with Se or vit E. 

PMID- 25395603
TI  - Public health research in the UK: in response to McCarthy et al.

PMID- 25395604
TI  - Friday sermons, family planning and gender equity attitudes and actions: evidence
      from Jordan.
AB  - BACKGROUND: To assess the effects of a communication intervention designed to
      enhance Jordanian religious leaders' (RLs) communication about family health.
      METHODS: Programmatic effects on RLs were evaluated with a panel study design;
      245 male and 145 female RLs participated in both baseline and end-line surveys in
      2011. To assess effects on mosque attendees, a nonequivalent, post-intervention
      only with control group design was utilized; 431 intervention and 426 control
      respondents were interviewed in 2012. RESULTS: Although RLs in the intervention
      site reported higher levels of preaching and teaching about the family health
      topics at end line than at baseline, their congregants were no more likely than
      control congregants to report having heard such messages over the previous 6
      month period, contrary to the anticipated outcome. Yet, intervention congregants
      compared with controls were more likely to take action related to the topics to
      which they were exposed. CONCLUSIONS: Despite the mixed findings, intervention
      mosque goers who recalled messages were more likely to report taking relevant
      actions. These findings suggest that trained RLs compared with their counterparts
      were more effective in message dissemination. Thus, the findings support broader
      implementation of this type of intervention once the programmatic changes
      recommended in this article are made.

PMID- 25395608
TI  - Complicated malaria and a covert ruptured spleen: a case report.
AB  - Spontaneous splenic rupture in complicated malaria is an uncommon cause of
      hemoperitoneum in the tropics. The exact incidence of splenic rupture is unknown,
      largely due to under-reporting, but has been estimated at ~2%. Its
      pathophysiology is linked to the formation of a subcapsular hematoma. Upon
      rupture, patients present with features of shock and peritonitis and in most
      cases (95%), computed tomography (CT) scan detects the splenic injury. Patients
      should be managed conservatively with splenectomy reserved for patients with
      shock and hemoperitoneum due to risk of post-splenectomy sepsis. We report the
      case of a 38-year-old man with severe malaria who presented with fever, chills
      and abdominal pains. A CT scan abdomen failed to reveal splenic parenchymal
      injury or any splenic extravasation of contrast. Conservative management was
      unsuccessful. Exploratory laparatomy confirmed the spleen as the site of bleeding
      necessitating a splenectomy. 

PMID- 25395609
TI  - Evaluation of hypoallergenicity of a new, amino acid-based formula.
AB  - The American Academy of Pediatrics (AAP) defined a formula as hypoallergenic if
      it ensures with 95% confidence that 90% of infants with confirmed cow's milk
      allergy (CMA) will not react with defined symptoms under double-blind, placebo
      controlled conditions. This study's objective was to determine whether a new
      amino acid-based formula (AAF) meets the AAP hypoallergenicity criteria. METHODS:
      Children with CMA were randomized to double-blind placebo-controlled food
      challenges (DBPCFC) with a new AAF and a commercial AAF in crossover fashion
      followed by an at-home open challenge with the new AAF. Allergic reactions were
      assessed using a scoring system. RESULTS: Thirty-three subjects completed DBPCFCs
      with both formulas without acute allergic reactions. The lower bound 95%
      confidence interval for hypoallergenicity was 91.3%. No unusual stool patterns,
      allergic symptoms, or signs of intolerance were reported during the open
      challenge. CONCLUSION: . The new AAF meets AAP hypoallergenicity criteria and can
      be recommended for the management of CMA.

PMID- 25395610
TI  - Waist circumference to height ratio in children and adolescents.
AB  - BACKGROUND: Waist circumference (WC) to height ratio (WC/HT) is used as a measure
      of central obesity. However, the optimum ratio that will separate populations
      with high from low cardiovascular risk remains controversial. This investigation
      evaluates an optimum WC/HT value to define central obesity in children. METHODS:
      The sensitivity and specificity of WC/HT in 649 children (age 2-18 years) without
      evidence of heart disease were analyzed for WC and for body mass index (BMI).
      RESULTS: A WC/HT >=0.5 resulted in sensitivity:specificity of 99%:72% for
      detecting central obesity and 83%:77% for detecting overweight (BMI >=85th
      percentile) subjects. A value of WC/HT >=0.55 yielded sensitivity:specificity of
      80%:96% for detecting central obesity and 75%:94% for detecting subjects with
      obesity (BMI >=95th percentile). CONCLUSIONS: The use of WC/HT between >=0.5 and
      <0.55 identified subjects at-risk for central obesity and WC/HT >=0.55 identified
      central obesity with a high probability.

PMID- 25395611
TI  - Risk Factors Associated With Abscess Formation in Children 5 Years of Age and
      Younger.
AB  - From 1997 to 2009, hospitalization rates have doubled for pediatric patients with
      soft tissue abscesses requiring incision and drainage. Despite this increasing
      national burden, few studies have been conducted to identify the risk factors
      associated with abscess formation. Our study evaluates a collection of
      physiological and lifestyle parameters that may serve as risk factors for abscess
      formation among pediatric patients 5 years of age or younger. Our results
      indicate family history and age 2 years and younger are associated with higher
      risk of abscess formation. Furthermore, methicillin-resistant Staphylococcus
      aureus and methicillin-susceptible Staphylococcus aureus were prevalent pathogens
      associated with abscess in our study group. Pediatricians may employ these novel
      parameters to educate parents and/or guardians of high-risk groups on preventing
      abscess formation to alleviate the burden of incision & dragining requiring
      abscess on health care costs. 

PMID- 25395612
TI  - Erratum.

PMID- 25395613
TI  - Lipolysis, and not hepatic lipogenesis, is the primary modulator of triglyceride
      levels in streptozotocin-induced diabetic mice.
AB  - OBJECTIVE: Diabetic hypertriglyceridemia is thought to be primarily driven by
      increased hepatic de novo lipogenesis. However, experiments in animal models
      indicated that insulin deficiency should decrease hepatic de novo lipogenesis and
      reduce plasma triglyceride levels. APPROACH AND RESULTS: To address the
      discrepancy between human data and genetically altered mouse models, we
      investigated whether insulin-deficient diabetic mice had triglyceride changes
      that resemble those in diabetic humans. Streptozotocin-induced insulin deficiency
      increased plasma triglyceride levels in mice. Contrary to the mouse models with
      impaired hepatic insulin receptor signaling, insulin deficiency did not reduce
      hepatic triglyceride secretion and de novo lipogenesis-related gene expression.
      Diabetic mice had a marked decrease in postprandial triglycerides clearance,
      which was associated with decreased lipoprotein lipase and peroxisome
      proliferator-activated receptor alpha mRNA levels in peripheral tissues and
      decreased lipoprotein lipase activity in skeletal muscle, heart, and brown
      adipose tissue. Diabetic heterozygous lipoprotein lipase knockout mice had
      markedly elevated fasting plasma triglyceride levels and prolonged postprandial
      triglycerides clearance. CONCLUSIONS: Insulin deficiency causes
      hypertriglyceridemia by decreasing peripheral lipolysis and not by an increase in
      hepatic triglycerides production and secretion.

PMID- 25395614
TI  - In vivo nanoparticle assessment of pathological endothelium predicts the
      development of inflow stenosis in murine arteriovenous fistula.
AB  - OBJECTIVE: In vivo assessment of pathological endothelium within arteriovenous
      fistula (AVF) could provide new insights into inflow stenosis, a common cause of
      AVF primary failure in end-stage renal disease patients. Here we developed
      nanoparticle-based imaging strategies to assess pathological endothelium in vivo
      and elucidate its relationship to neointimal hyperplasia formation in AVF.
      APPROACH AND RESULTS: Jugular-carotid AVFs were created in C57BL/6 mice (n=38).
      Pathological endothelium in the AVF was visualized and quantified in vivo using
      dextranated magnetofluorescent nanoparticles (CLIO-VT680 [cross-linked iron oxide
      VivoTag680]). At day 14, CLIO-VT680 was deposited in AVF, but only minimally in
      sham-operated arteries. Transmission electron microscopy revealed that CLIO-VT680
      resided within endothelial cells and in the intimal extracellular space.
      Endothelial cells of AVF, but not control arteries, expressed vascular cell
      adhesion molecule-1 and showed augmented endothelial permeability near the
      anastomosis. Intravital microscopy demonstrated that CLIO-VT680 deposited most
      intensely near the AVF anastomosis (P<0.0001). The day 14 intravital microscopy
      CLIO-VT680 signal predicted the subsequent site and magnitude of AVF neointimal
      hyperplasia at day 42 (r=0.58, P<0.05). CLIO-VT680 deposition in AVF was further
      visualized by ex vivo MRI. CONCLUSIONS: AVF develop a pathological endothelial
      response that can be assessed in vivo via nanoparticle-enhanced imaging. AVF
      endothelium is activated and exhibits augmented permeability, offering a
      targeting mechanism for nanoparticle deposition and retention in pathological
      endothelium. The in vivo AVF nanoparticle signal identified and predicted
      subsequent inflow neointimal hyperplasia. This approach could be used to test
      therapeutic interventions aiming to restore endothelial health and to decrease
      early AVF failure caused by inflow stenosis.

PMID- 25395615
TI  - Smooth muscle cell deletion of low-density lipoprotein receptor-related protein 1
      augments angiotensin II-induced superior mesenteric arterial and ascending aortic
      aneurysms.
AB  - OBJECTIVE: Low-density lipoprotein receptor-related protein 1 (LRP1), a
      multifunctional protein involved in endocytosis and cell signaling pathways,
      leads to several vascular pathologies when deleted in vascular smooth muscle
      cells (SMCs). The purpose of this study was to determine whether LRP1 deletion in
      SMCs influenced angiotensin II-induced arterial pathologies. APPROACH AND
      RESULTS: LRP1 protein abundance was equivalent in selected arterial regions, but
      SMC-specific LRP1 depletion had no effect on abdominal and ascending aortic
      diameters in young mice. To determine the effects of LRP1 deficiency on
      angiotensin II vascular responses, SMC-specific LRP1 (smLRP1(+/+)) and smLRP1
      deficient (smLRP1(-/-)) mice were infused with saline, angiotensin II, or
      norepinephrine. Several smLRP(-/-) mice died of superior mesenteric arterial
      (SMA) rupture during angiotensin II infusion. In surviving mice, angiotensin II
      profoundly augmented SMA dilation in smLRP1(-/-) mice. SMA dilation was blood
      pressure dependent as demonstrated by a similar response during norepinephrine
      infusion. SMA dilation was also associated with profound macrophage accumulation,
      but minimal elastin fragmentation. Angiotensin II infusion led to no significant
      differences in abdominal aorta diameters between smLRP1(+/+) and smLRP1(-/-)
      mice. In contrast, ascending aortic dilation was exacerbated markedly in
      angiotensin II-infused smLRP1(-/-) mice, but norepinephrine had no significant
      effect on either aortic region. Ascending aortas of smLRP1(-/-) mice infused with
      angiotensin II had minimal macrophage accumulation but significantly increased
      elastin fragmentation and mRNA abundance of several LRP1 ligands including MMP-2
      (matrix metalloproteinase-2) and uPA (urokinase plasminogen activator).
      CONCLUSIONS: smLRP1 deficiency had no effect on angiotensin II-induced abdominal
      aortic aneurysm formation. Conversely, angiotensin II infusion in smLRP1(-/-)
      mice exacerbated SMA and ascending aorta dilation. Dilation in these 2 regions
      had differential association with blood pressure and divergent pathological
      characteristics.

PMID- 25395616
TI  - Leukocyte cathepsin C deficiency attenuates atherosclerotic lesion progression by
      selective tuning of innate and adaptive immune responses.
AB  - OBJECTIVE: The protein degrading activity of cathepsin C (CatC), combined with
      its role in leukocyte granule activation, suggests a contribution of this cystein
      protease in atherosclerosis. However, no experimental data are available to
      validate this concept. APPROACH AND RESULTS: CatC gene and protein expression
      were increased in ruptured versus advanced stable human carotid artery lesions.
      To assess causal involvement of CatC in plaque progression and stability, we
      generated LDLr(-/-)//CatC(-/-) chimeras by bone marrow transplantation. CatC(-/-)
      chimeras presented attenuated plaque burden in carotids, descending aorta, aortic
      arch and root, at both the early and advanced plaque stage. CatC was abundantly
      expressed by plaque macrophages and foam cells. CatC expression and activity were
      dramatically downregulated in plaques of CatC(-/-) chimeras, supporting a
      hematopoietic origin of plaque CatC. Our studies unveiled an unexpected feedback
      of CatC deficiency on macrophage activation programs and T helper cell
      differentiation in as much as that CatC expression was upregulated in M1
      macrophages, whereas its deficiency led to combined M2 (in vitro) and Th2
      polarization (in vivo). CONCLUSIONS: Our data implicate CatC has a role in the
      selective tuning of innate and adaptive immune responses, relevant to a chronic
      immune disease, such as atherosclerosis.

PMID- 25395617
TI  - Protein tyrosine phosphatase 1B impairs diabetic wound healing through vascular
      endothelial growth factor receptor 2 dephosphorylation.
AB  - OBJECTIVE: Impaired wound healing is a major complication of diabetes mellitus.
      The mechanisms that govern wound healing, however, are complex and incompletely
      understood. In the present study, we determined the inhibitory role of protein
      tyrosine phosphatase 1B (PTP1B) in the process of diabetic wound healing.
      APPROACH AND RESULTS: First, by comparing the wound healing process in PTP1B
      knockout (PTP1B(-/-)) mice, ob/ob mice and their wild-type littermates in the
      presence or absence of streptozotocin treatment, we showed that the inhibition of
      mouse wound healing in streptozotocin-induced diabetic conditions is because of
      the upregulation and activation of PTP1B. Second, the impaired wound healing in
      ob/ob mice and streptozotocin-treated wild-type mice was rescued by a PTP1B
      inhibitor. Third, PTP1B, which is upregulated under hyperglycemic condition,
      inhibited the tube formation, proliferation, and migration of human microvascular
      endothelial cells induced by vascular endothelial growth factor, whereas this
      inhibition was largely abolished by the PTP1B inhibitor. Finally, mechanism study
      further indicated that PTP1B likely suppressed the proliferation, migration, and
      tube formation of vascular endothelial cells through dephosphorylation of
      vascular endothelial growth factor receptor 2. CONCLUSIONS: Our study
      demonstrated that PTP1B negatively modulated the diabetic wound healing process
      by dephosphorylating the endothelial cell vascular endothelial growth factor
      receptor 2 and that the specific inhibitor of PTP1B might serve as a potential
      novel therapeutic tool for diabetic wound healing.

PMID- 25395618
TI  - Induction of dendritic cell-mediated T-cell activation by modified but not native
      low-density lipoprotein in humans and inhibition by annexin a5: involvement of
      heat shock proteins.
AB  - OBJECTIVE: Atherosclerosis is an inflammatory disease, where activated
      immunocompetent cells, including dendritic cells (DCs) and T cells are abundant
      in plaques. Low-density lipoprotein modified either by oxidation (oxLDL) or by
      human group X-secreted phospholipase A2 (LDLx) and heat shock proteins (HSP),
      especially HSP60 and 90, have been implicated in atherosclerosis. We previously
      reported that Annexin A5 inhibits inflammatory effects of phospholipids,
      decreases vascular inflammation and improves vascular function in apolipoprotein
      E(-/-) mice. Here, we focus on the LDLx effects on human DCs and T cells.
      APPROACH AND RESULTS: Human DCs were differentiated from peripheral blood
      monocytes, stimulated by oxLDL or LDLx. Naive autologous T cells were cocultured
      with pretreated DCs. oxLDL and LDLx, in contrast to LDL, induced DC-activation
      and T-cell proliferation. T cells exposed to LDLx-treated DCs produced interferon
      gamma, interleukin (IL)-17 but not IL-4 and IL-10. Annexin A5 abrogated LDLx
      effects on DCs and T cells and increased production of transforming growth factor
      beta and IL-10. Furthermore, IL-10 producing T cells suppressed primary T-cell
      activation via soluble IL-10, transforming growth factor-beta, and cell-cell
      contact. Lentiviral-mediated shRNA knock-down HSP60 and 90 in DCs attenuated the
      effect of LDLx on DCs and subsequent T-cell proliferation. Experiments on DC and
      T cells derived from carotid atherosclerotic plaques gave similar results.
      CONCLUSIONS: Our data show that modified forms of LDL such as LDLx but not native
      LDL activate human T cells through DCs. HSP60 and 90 contribute to such T-cell
      activation. Annexin A5 promotes induction of regulatory T cells and is
      potentially interesting as a therapeutic agent.

PMID- 25395619
TI  - G-protein estrogen receptor as a regulator of low-density lipoprotein cholesterol
      metabolism: cellular and population genetic studies.
AB  - OBJECTIVE: Estrogen deficiency is linked with increased low-density lipoprotein
      (LDL) cholesterol. The hormone receptor mediating this effect is unknown. G
      protein estrogen receptor (GPER) is a recently recognized G-protein-coupled
      receptor that is activated by estrogens. We recently identified a common
      hypofunctional missense variant of GPER, namely P16L. However, the role of GPER
      in LDL metabolism is unknown. Therefore, we examined the association of the P16L
      genotype with plasma LDL cholesterol level. Furthermore, we studied the role of
      GPER in regulating expression of the LDL receptor and proprotein convertase
      subtilisin kexin type 9. APPROACH AND RESULTS: Our discovery cohort was a
      genetically isolated population of Northern European descent, and our validation
      cohort consisted of normal, healthy women aged 18 to 56 years from London,
      Ontario. In addition, we examined the effect of GPER on the regulation of
      proprotein convertase subtilisin kexin type 9 and LDL receptor expression by the
      treatment with the GPER agonist, G1. In the discovery cohort, GPER P16L genotype
      was associated with a significant increase in LDL cholesterol (mean+/-SEM):
      3.18+/-0.05, 3.25+/-0.08, and 4.25+/-0.33 mmol/L, respectively, in subjects with
      CC (homozygous for P16), CT (heterozygotes), and TT (homozygous for L16)
      genotypes (P<0.05). In the validation cohort (n=339), the GPER P16L genotype was
      associated with a similar increase in LDL cholesterol: 2.17+/-0.05, 2.34+/-0.06,
      and 2.42+/-0.16 mmol/L, respectively, in subjects with CC, CT, and TT genotypes
      (P<0.05). In the human hepatic carcinoma cell line, the GPER agonist, G1,
      mediated a concentration-dependent increase in LDL receptor expression, blocked
      by either pretreatment with the GPER antagonist G15 or by shRNA-mediated GPER
      downregulation. G1 also mediated a GPER- and concentration-dependent decrease in
      proprotein convertase subtilisin kexin type 9 expression. CONCLUSIONS: GPER
      activation upregulates LDL receptor expression, probably at least, in part, via
      proprotein convertase subtilisin kexin type 9 downregulation. Furthermore, humans
      carrying the hypofunctional P16L genetic variant of GPER have increased plasma
      LDL cholesterol. In aggregate, these data suggest an important role of GPER in
      the regulation of LDL receptor expression and consequently LDL metabolism.

PMID- 25395620
TI  - Cysteinyl leukotriene 1 receptors as novel mechanosensors mediating myogenic tone
      together with angiotensin II type 1 receptors-brief report.
AB  - OBJECTIVE: Myogenic vasoconstriction is mediated by vascular smooth muscle cells
      of resistance arteries sensing mechanical stretch. Angiotensin II AT1 receptors
      and in particular AT1BRs in murine vascular smooth muscle cells have been
      characterized as mechanosensors that cannot fully account for myogenic
      vasoconstriction observed. Therefore, we aimed at uncovering novel vascular
      mechanosensors by expression profiling and functional characterization of
      candidate proteins. APPROACH AND RESULTS: Analyzing myogenic tone of isolated
      murine mesenteric arteries of AT1A and AT1B receptor double gene-deficient
      (AT1A/1B (-/-)) mice ex vivo, we observed a decreased myogenic tone at high
      intraluminal pressures and an unexpected hyper-reactivity at low intraluminal
      pressures because of upregulation of cysteinyl leukotriene 1 receptors
      (CysLT1Rs). Pharmacological blockade of CysLT1Rs with pranlukast significantly
      reduced myogenic tone not only in AT1A/1B (-/-) but also in wild-type arteries.
      In wild-type arteries, additional blockade of angiotensin II AT1 receptors with
      candesartan resulted in an additive reduction of myogenic tone. Furthermore,
      calcium imaging experiments were performed with fura-2-loaded human embryonic
      kidney 293 cells overexpressing CysLT1Rs and with isolated mesenteric vascular
      smooth muscle cells. Hypo-osmotically induced membrane stretch provoked calcium
      transients that were significantly reduced by pranlukast. Incubations of isolated
      mesenteric vascular smooth muscle cells with the 5-lipoxygenase inhibitor
      zileuton had no effect. Furthermore, the Gq/11-protein inhibitor YM 254890
      profoundly reduced myogenic tone to the same extent as induced by the application
      of pranlukast plus candesartan. CONCLUSIONS: Here, we identify a novel, hitherto
      unappreciated role of CysLT1Rs in vascular regulation. We identified CysLT1Rs as
      novel mechanosensors in the vasculature involved in myogenic vasoconstriction.
      Moreover, our findings suggest that myogenic tone is determined by AT1 and CysLT1
      receptors acting together as mechanosensors via Gq/11-protein activation.

PMID- 25395621
TI  - A switch between one- and two-electron chemistry of the human flavoprotein
      iodotyrosine deiodinase is controlled by substrate.
AB  - Reductive dehalogenation is not typical of aerobic organisms but plays a
      significant role in iodide homeostasis and thyroid activity. The flavoprotein
      iodotyrosine deiodinase (IYD) is responsible for iodide salvage by reductive
      deiodination of the iodotyrosine derivatives formed as byproducts of thyroid
      hormone biosynthesis. Heterologous expression of the human enzyme lacking its N
      terminal membrane anchor has allowed for physical and biochemical studies to
      identify the role of substrate in controlling the active site geometry and flavin
      chemistry. Crystal structures of human IYD and its complex with 3-iodo-l-tyrosine
      illustrate the ability of the substrate to provide multiple interactions with the
      isoalloxazine system of FMN that are usually provided by protein side chains.
      Ligand binding acts to template the active site geometry and significantly
      stabilize the one-electron-reduced semiquinone form of FMN. The neutral form of
      this semiquinone is observed during reductive titration of IYD in the presence of
      the substrate analog 3-fluoro-l-tyrosine. In the absence of an active site
      ligand, only the oxidized and two-electron-reduced forms of FMN are detected. The
      pH dependence of IYD binding and turnover also supports the importance of direct
      coordination between substrate and FMN for productive catalysis. 

PMID- 25395622
TI  - Expression of the ORMDLS, modulators of serine palmitoyltransferase, is regulated
      by sphingolipids in mammalian cells.
AB  - The relationship between serine palmitoyltransferase (SPT) activity and ORMDL
      regulation of sphingolipid biosynthesis was investigated in mammalian HEK293
      cells. Each of the three human ORMDLs reduced the increase in long-chain base
      synthesis seen after overexpression of wild-type SPT or SPT containing the C133W
      mutation in hLCB1, which produces the non-catabolizable sphingoid base, 1
      deoxySa. ORMDL-dependent repression of sphingoid base synthesis occurred whether
      SPT was expressed as individual subunits or as a heterotrimeric single-chain SPT
      fusion protein. Overexpression of the single-chain SPT fusion protein under the
      control of a tetracycline-inducible promoter in stably transfected cells resulted
      in increased endogenous ORMDL expression. This increase was not transcriptional;
      there was no significant increase in any of the ORMDL mRNAs. Increased ORMDL
      protein expression required SPT activity since overexpression of a catalytically
      inactive SPT with a mutation in hLCB2a had little effect. Significantly,
      increased ORMDL expression was also blocked by myriocin inhibition of SPT as well
      as fumonisin inhibition of the ceramide synthases, suggesting that increased
      expression is a response to a metabolic signal. Moreover, blocking ORMDL
      induction with fumonisin treatment resulted in significantly greater increases in
      in vivo SPT activity than was seen when ORMDLs were allowed to increase,
      demonstrating the physiological significance of this response. 

PMID- 25395623
TI  - Unfolded protein response-regulated Drosophila Fic (dFic) protein reversibly
      AMPylates BiP chaperone during endoplasmic reticulum homeostasis.
AB  - Drosophila Fic (dFic) mediates AMPylation, a covalent attachment of adenosine
      monophosphate (AMP) from ATP to hydroxyl side chains of protein substrates. Here,
      we identified the endoplasmic reticulum (ER) chaperone BiP as a substrate for
      dFic and mapped the modification site to Thr-366 within the ATPase domain. The
      level of AMPylated BiP in Drosophila S2 cells is high during homeostasis, whereas
      the level of AMPylated BiP decreases upon the accumulation of misfolded proteins
      in the ER. Both dFic and BiP are transcriptionally activated upon ER stress,
      supporting the role of dFic in the unfolded protein response pathway. The
      inactive conformation of BiP is the preferred substrate for dFic, thus endorsing
      a model whereby AMPylation regulates the function of BiP as a chaperone, allowing
      acute activation of BiP by deAMPylation during an ER stress response. These
      findings not only present the first substrate of eukaryotic AMPylator but also
      provide a target for regulating the unfolded protein response, an emerging avenue
      for cancer therapy. 

PMID- 25395625
TI  - Complete Genome Sequence of vB_EcoM_112, a T-Even-Type Bacteriophage Specific for
      Escherichia coli O157:H7.
AB  - Bacteriophage vB_EcoM_112 (formerly e11/2) is an Escherichia coli phage with
      specificity for the O157:H7 serotype. The vB_EcoM_112 genome sequence shares high
      degrees of similarity with the phage T4 genome sequence. 

PMID- 25395626
TI  - Complete Mitochondrial DNA Sequence of the Mucoralean Fusion Parasite Parasitella
      parasitica.
AB  - The complete mitochondrial DNA sequence of the Mucor-related fungus Parasitella
      parasitica has been sequenced. It has a G+C content of 30% and a total length of
      83,361 bp. All protein-coding genes normally found in fungi are present in the
      sequence. A special feature is the remarkably high number of 27 homing
      endonucleases. 

PMID- 25395624
TI  - Development and characterization of pepducins as Gs-biased allosteric agonists.
AB  - The beta2-adrenergic receptor (beta2AR) is a prototypical G protein-coupled
      receptor that mediates many hormonal responses, including cardiovascular and
      pulmonary function. beta-Agonists used to combat hypercontractility in airway
      smooth muscle stimulate beta2AR-dependent cAMP production that ultimately
      promotes airway relaxation. Chronic stimulation of the beta2AR by long acting
      beta-agonists used in the treatment of asthma can promote attenuated
      responsiveness to agonists and an increased frequency of fatal asthmatic attacks.
      beta2AR desensitization to beta-agonists is primarily mediated by G protein
      coupled receptor kinases and beta-arrestins that attenuate receptor-Gs coupling
      and promote beta2AR internalization and degradation. A biased agonist that can
      selectively stimulate Gs signaling without promoting receptor interaction with G
      protein-coupled receptor kinases and beta-arrestins should serve as an
      advantageous asthma therapeutic. To identify such molecules, we screened ~50
      lipidated peptides derived from the intracellular loops of the beta2AR, known as
      pepducins. This screen revealed two classes of Gs-biased pepducins, receptor
      independent and receptor-dependent, as well as several beta-arrestin-biased
      pepducins. The receptor-independent Gs-biased pepducins operate by directly
      stimulating G protein activation. In contrast, receptor-dependent Gs-biased
      pepducins appear to stabilize a Gs-biased conformation of the beta2AR that
      couples to Gs but does not undergo G protein-coupled receptor kinase-mediated
      phosphorylation or beta-arrestin-mediated internalization. Functional studies in
      primary human airway smooth muscle cells demonstrate that Gs-biased pepducins are
      not subject to conventional desensitization and thus may be good candidates for
      the development of next generation asthma therapeutics. Our study reports the
      first Gs-biased activator of the beta2AR and provides valuable tools for the
      study of beta2AR function. 

PMID- 25395627
TI  - Pacui Virus, Rio Preto da Eva Virus, and Tapirape Virus, Three Distinct Viruses
      within the Family Bunyaviridae.
AB  - Nearly complete genome sequences for three ungrouped viruses, Pacui virus
      (BEAN27326), Rio Preto da Eva virus (BEAR540870), and Tapirape virus (BEAN767592)
      isolated in the Amazon region are reported here. All three genomic segments
      (small, medium and large RNA) were recovered and were similar to members of the
      genus Orthobunyavirus. 

PMID- 25395628
TI  - Genome Sequence of Corynebacterium pseudotuberculosis MB20 bv. equi Isolated from
      a Pectoral Abscess of an Oldenburg Horse in California.
AB  - The genome of Corynebacterium pseudotuberculosis MB20 bv. equi was sequenced
      using the Ion Personal Genome Machine (PGM) platform, and showed a size of
      2,363,089 bp, with 2,365 coding sequences and a GC content of 52.1%. These
      results will serve as a basis for further studies on the pathogenicity of C.
      pseudotuberculosis bv. equi. 

PMID- 25395629
TI  - Draft Genome Sequence of Bacillus megaterium Type Strain ATCC 14581.
AB  - Bacillus megaterium is a Gram-positive, rod-shaped, spore-forming bacterium of
      biotechnological importance. Here, we report a 5.7-Mbp draft genome sequence of
      B. megaterium ATCC 14581, which is the type strain of the species. 

PMID- 25395630
TI  - Complete Genome Sequences of Beijing and Manila Family Strains of Mycobacterium
      tuberculosis.
AB  - The majority of isolates from tuberculosis patients in Hawaii arrive through the
      immigration of infected individuals from the western Pacific. We report here on
      the annotated complete genomes of two strains of Mycobacterium tuberculosis from
      the two main lineages/families in Hawaii, Beijing and Manila. 

PMID- 25395631
TI  - Genome Sequence of "Thalassospira australica" NP3b2T Isolated from St. Kilda
      Beach, Tasman Sea.
AB  - Here, we present the draft genome of "Thalassospira australica" NP3b2(T), a
      potential poly(ethylene terephthalate) (PET) plastic biodegrader. This genomic
      information will enhance information on the genetic basis of metabolic pathways
      for the degradation of PET plastic. 

PMID- 25395632
TI  - Exploring the Genome of Cheese Starter Lactic Acid Bacterium Lactococcus lactis
      subsp. lactis CECT 4433.
AB  - Here, we present the draft genome sequences of Lactococcus lactis subsp. lactis
      CECT 4433, a cheese fermentation starter strain. The genome provides further
      insight into the genomic plasticity, biocomplexity (including gene strain
      specifics), and evolution of these genera. 

PMID- 25395633
TI  - Draft Genome Sequence of an Extensively Drug-Resistant Acinetobacter baumannii
      Indigo-Pigmented Strain.
AB  - Last year in 2013, we reported an outbreak due to indigo-pigmented Acinetobacter
      baumannii strains in a hospital from Buenos Aires, Argentina. Here, we present
      the draft genome sequence of one of the strains (A. baumannii A33405) involved in
      the outbreak. This isolate was categorized as extensively drug-resistant (XDR)
      and harbors different genetic elements associated with horizontal genetic
      transfer and multiple antibiotic resistances. 

PMID- 25395634
TI  - Draft Genome Sequence of Lactobacillus plantarum CMPG5300, a Human Vaginal
      Isolate.
AB  - The draft genome of a highly auto-aggregating Lactobacillus plantarum strain
      isolated from a human vagina is reported. The peculiar phenotype also provides an
      adhesive and co-aggregative potential with various pathogens, which could be of
      significance in the vaginal niche. Detailed genome analysis could aid in
      identifying the adhesins of the strain. 

PMID- 25395635
TI  - Complete Nucleotide Sequence of a Citrobacter freundii Plasmid Carrying KPC-2 in
      a Unique Genetic Environment.
AB  - The complete and annotated nucleotide sequence of a 54,036-bp plasmid harboring a
      blaKPC-2 gene that is clonally present in Citrobacter isolates from different
      species is presented. The plasmid belongs to incompatibility group N (IncN) and
      harbors the class A carbapenemase KPC-2 in a unique genetic environment. 

PMID- 25395636
TI  - Nearly complete genome sequence of curionopolis virus, a culicoides-related
      rhabdovirus isolated in the brazilian Amazon region.
AB  - We report here the first nearly complete genome sequence related to curionopolis
      virus (CURV), that of strain AR440009, isolated from a pool of Culicoides sp.
      midges in Serra Norte, Para State, northern Brazil. All genes showed similarities
      to those belonging to members of the family Rhabdoviridae. 

PMID- 25395637
TI  - Genome Sequence of the Anterograde-Spread-Defective Herpes Simplex Virus 1 Strain
      MacIntyre.
AB  - We used paired-end Illumina deep sequencing and de novo assembly to determine the
      genome sequence of herpes simplex virus 1 (HSV-1) strain MacIntyre (aka
      McIntyre). The MacIntyre strain originated from the brain of a patient with
      lethal HSV encephalitis and has a unique limitation in its neuronal spread,
      moving solely in the retrograde direction. 

PMID- 25395638
TI  - Complete Genome Sequence of Dyella japonica Strain A8 Isolated from Malaysian
      Tropical Soil.
AB  - We previously identified and presented the draft genome of a Xanthomonadaceae
      bacterial strain Dyella japonica A8 which shows quorum-quenching activity. Here,
      we report the complete, closed genome sequence of this bacterium. This complete
      genome may help to further investigate the comparative quorum-quenching activity
      among D. japonica strains. 

PMID- 25395639
TI  - Draft Genome Sequences of Marine Flavobacterium Nonlabens Strains NR17, NR24,
      NR27, NR32, NR33, and Ara13.
AB  - Here, we present the draft genome sequences of six carotenoid producers
      affiliated with Nonlabens spp. isolated from marine environments in both the
      northern and southern parts of Japan. The genomic information will help to
      elucidate the function and evolution of carotenoid synthetic gene clusters not
      only in the genus Nonlabens but also in the family Flavobacteriaceae. 

PMID- 25395640
TI  - Draft Genome Sequences of Marine Flavobacterium Algibacter lectus Strains SS8 and
      NR4.
AB  - Here, we present the draft genome sequences of a zeaxanthin-producing
      flavobacterium, Algibacter lectus strains SS8 and NR4, isolated from coastal
      sediment and rock surfaces in Hakodate, Japan, respectively. This genomic
      information represents the first Algibacter genome sequences, which will help us
      to elucidate the biology and evolution of Flavobacteriaceae bacteria. 

PMID- 25395641
TI  - Metagenome sequencing of the microbial community of a solar saltern crystallizer
      pond at cahuil lagoon, chile.
AB  - Cahuil Lagoon in central Chile harbors distinct microbial communities in various
      solar salterns that are arranged as interconnected ponds with increasing salt
      concentrations. Here, we report the metagenome of the 3.0- to 0.2-um fraction of
      the microbial community present in a crystallizer pond with 34% salinity. 

PMID- 25395642
TI  - Whole-Genome Sequencing and Mutation Analysis of Two Extensively Drug-Resistant
      Sputum Isolates of Mycobacterium tuberculosis (VRFCWCF XDRTB 232 and VRFCWCF
      XDRTB 1028) from Chennai, India.
AB  - We announce the draft genome sequence of two extensively drug-resistant
      Mycobacterium tuberculosis strains, VRFCWCF XDRTB 232 and VRFCWCF XDRTB 1028,
      isolated from the sputum samples of a patient clinically suspected to have
      tuberculosis, and we also report novel mutations that confer drug resistance. 

PMID- 25395643
TI  - Draft Genome Sequence of Bacillus alcalophilus AV1934, a Classic Alkaliphile
      Isolated from Human Feces in 1934.
AB  - Bacillus alcalophilus AV1934, isolated from human feces, was described in 1934
      before microbiome studies and recent indications of novel potassium ion coupling
      to motility in this extremophile. Here, we report draft sequences that will
      facilitate an examination of whether that coupling is part of a larger cycle of
      potassium ion-coupled transporters. 

PMID- 25395644
TI  - Genome Sequences of Lactobacillus sp. Strains wkB8 and wkB10, Members of the Firm
      5 Clade, from Honey Bee Guts.
AB  - We sequenced two strains from the Lactobacillus Firm-5 clade, a dominant group of
      symbionts in the guts of honey bees and other social bees. The genome of strain
      wkB8, comprising a 1.93-Mb chromosome and a 6.4-kb plasmid, was fully closed,
      while strain wkB10 was assembled into 32 contigs. These genomes will provide
      insights into how gut symbionts evolve and interact with their host species. 

PMID- 25395645
TI  - Draft Genome Sequence of the Mercury-Resistant Bacterium Acinetobacter
      idrijaensis Strain MII, Isolated from a Mine-Impacted Area, Idrija, Slovenia.
AB  - We report here the first draft assembly for the genome of Acinetobacter
      idrijaensis strain MII, isolated from the Idrija mercury mine area (Slovenia).
      This strain shows a strikingly high tolerance to mercury, and the genome sequence
      shows genes involved in the mechanisms for heavy metal tolerance pathways and
      multidrug efflux pumps. 

PMID- 25395646
TI  - Complete Genome Sequence of the Multiresistant Acinetobacter baumannii Strain
      AbH12O-A2, Isolated during a Large Outbreak in Spain.
AB  - We report the complete genome sequence of Acinetobacter baumannii strain AbH12O
      A2, isolated during a large outbreak in Spain. The genome has 3,875,775 bp and
      3,526 coding sequences, with 39.4% G+C content. The availability of this genome
      will facilitate the study of the pathogenicity of the Acinetobacter species. 

PMID- 25395647
TI  - The Draft Genome Sequence of Sphingomonas sp. Strain FukuSWIS1, Obtained from
      Acidic Lake Grosse Fuchskuhle, Indicates Photoheterotrophy and a Potential for
      Humic Matter Degradation.
AB  - Sphingomonas spp. are Alphaproteobacteria considered to be versatile bacteria
      that can utilize a variety of natural substrates available in terrestrial and
      aquatic systems. Sphingomonas sp. strain FukuSWIS1 was isolated from the
      eutrophic and acidic freshwater Lake Grosse Fuchskuhle in northeastern Germany.
      The strain has a genome size of 3.89 Mb, possesses a set of photosynthetic genes,
      and expresses photopigment BChl a under oxic conditions. Thus, this strain
      belongs to the aerobic anoxygenic phototrophic (AAP) bacteria, which are most
      likely involved in humic matter degradation as indicated by the presence of
      organic compound mineralizing genes. 

PMID- 25395648
TI  - Genome Sequence of Tumebacillus flagellatus GST4, the First Genome Sequence of a
      Species in the Genus Tumebacillus.
AB  - We present here the first genome sequence of a species in the genus Tumebacillus.
      The draft genome sequence of Tumebacillus flagellatus GST4 provides a genetic
      basis for future studies addressing the origins, evolution, and ecological role
      of Tumebacillus organisms, as well as a source of acid-resistant amylase-encoding
      genes for further studies. 

PMID- 25395650
TI  - Draft Genome Sequence of Microvirga sp. Strain BSC39, Isolated from Biological
      Soil Crust of Moab, Utah.
AB  - Microvirga sp. BSC39 was isolated from a biological soil crust near Moab, Utah.
      The strain appears to be capable of chemotaxis and exopolysaccharide synthesis
      for biofilm adhesion. The BSC39 genome contains iron siderophore uptake and
      hydrolysis enzymes; however, it lacks siderophore synthesis pathways, suggesting
      the uptake of siderophores produced by neighboring microbes. 

PMID- 25395649
TI  - High-Quality Draft Genome Sequence of Babesia divergens, the Etiological Agent of
      Cattle and Human Babesiosis.
AB  - Babesia divergens causes significant morbidity and mortality in cattle and
      splenectomized or immunocompromised individuals. Here, we present a 10.7-Mb high
      quality draft genome of this parasite close to chromosome resolution that will
      enable comparative genome analyses and synteny studies among related parasites. 

PMID- 25395651
TI  - Draft Genome Sequence of Bacillus sp. Strain BSC154, Isolated from Biological
      Soil Crust of Moab, Utah.
AB  - Bacillus sp. BSC154 was isolated from a biological soil crust near Moab, Utah.
      The strain appears to be capable of chemotaxis and biofilm production. The BSC154
      genome contains iron siderophore production, nitrate reduction, mixed acid
      butanediol fermentation, and assimilatory and dissimilatory sulfate metabolism
      pathways. 

PMID- 25395652
TI  - Draft Genome Sequence of Massilia sp. Strain BSC265, Isolated from Biological
      Soil Crust of Moab, Utah.
AB  - Massilia sp. BSC265 was isolated from a biological soil crust near Moab, Utah.
      The strain appears to be capable of chemotaxis and exopolysaccharide synthesis
      for biofilm adhesion. The BSC265 genome contains a complete dissimilatory nitrate
      reduction pathway as well as a TCA cycle, making it a facultative anaerobe. 

PMID- 25395653
TI  - The educational gradient in coronary heart disease: the association with
      cognition in a cohort of 57,279 male conscripts.
AB  - BACKGROUND: Independently of cardiovascular disease (CVD) risk factors, cognitive
      ability may account for some of the excess risk of coronary heart disease (CHD)
      associated with lower education. We aimed to assess how late adolescence
      cognitive ability and midlife CVD risk factors are associated with the
      educational gradient in CHD in Norway. METHODS: In a cohort of 57 279 men born
      during 1949-1959, health survey information was linked to military conscription
      records of cognitive ability, to national educational data, to hospitalisation
      records from the Cardiovascular Disease in Norway (CVDNOR) project and to the
      Norwegian Cause of Death Registry. RESULTS: Age and period adjusted HR for
      incident CHD events was 3.62 (95% CI 2.50 to 5.24) for basic relative to tertiary
      education, and was attenuated after adjustment; to 2.86 (1.87 to 4.38) for
      cognitive ability, to 1.90 (1.30 to 2.78) for CVD risk factors, and to 1.84 (1.20
      to 2.83) when adjusting for both. Age and period adjusted absolute rate
      difference was 51 (33 to 70) incident CHD events per 100,000 person years between
      basic and tertiary educated, and was attenuated after adjustment; to 42 (22 to
      61) for cognitive ability, to 25 (7 to 42) for CVD risk factors, and to 24 (5 to
      43) when adjusting for both. CONCLUSIONS: Late adolescence cognitive ability
      attenuated the educational gradient in incident CHD events. CVD risk factors
      further attenuated the gradient, and to the same extent regardless of whether
      cognitive ability was included or not. Cognitive ability might be linked to the
      educational gradient through CVD risk factors.

PMID- 25395654
TI  - Preventing non-communicable diseases through structural changes in urban
      environments.

PMID- 25395655
TI  - Conscious sedation versus general anesthesia during endovascular acute ischemic
      stroke treatment: a systematic review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: A number of studies have suggested that anesthesia type
      (conscious sedation versus general anesthesia) during intra-arterial treatment
      for acute ischemic stroke has implications for patient outcomes. We performed a
      systematic review and meta-analysis of studies comparing the clinical and
      angiographic outcomes of the 2 anesthesia types. MATERIALS AND METHODS: In March
      2014, we conducted a computerized search of MEDLINE and EMBASE for reports on
      anesthesia and endovascular treatment of acute ischemic stroke. Using random
      effects meta-analysis, we evaluated the following outcomes: recanalization rate,
      good functional outcome (mRS <= 2), asymptomatic and symptomatic intracranial
      hemorrhage, death, vascular complications, respiratory complications, procedure
      time, time to groin, and time from symptom onset to recanalization. RESULTS: Nine
      studies enrolling 1956 patients (814 with general anesthesia and 1142 with
      conscious sedation) were included. Compared with patients treated by using
      conscious sedation during stroke intervention, patients undergoing general
      anesthesia had higher odds of death (OR = 2.59; 95% CI, 1.87-3.58) and
      respiratory complications (OR = 2.09; 95% CI, 1.36-3.23) and lower odds of good
      functional outcome (OR = 0.43; 95% CI, 0.35-0.53) and successful angiographic
      outcome (OR = 0.54; 95% CI, 0.37-0.80). No difference in procedure time (P = .28)
      was seen between the groups. Preintervention NIHSS scores were available from 6
      studies; in those, patients receiving general anesthesia had a higher average
      NIHSS score. CONCLUSIONS: Patients with acute ischemic stroke undergoing intra
      arterial therapy may have worse outcomes with general anesthesia compared with
      conscious sedation. However, the difference in stroke severity at the onset may
      confound the comparison in the available studies; thus, a randomized trial is
      necessary to confirm this association.

PMID- 25395656
TI  - Intramedullary spinal cord metastases: prognostic value of MRI and clinical
      features from a 13-year institutional case series.
AB  - BACKGROUND AND PURPOSE: In patients with intramedullary spinal cord metastases,
      the impact of MR imaging and clinical characteristics on survival has not been
      elucidated. Our aim was to identify MR imaging and clinical features with
      prognostic value among patients with intramedullary spinal cord metastases from a
      large retrospective series. MATERIALS AND METHODS: The relevant MR imaging
      examination and baseline clinical data for each patient from a consecutive group
      of patients with intramedullary spinal cord metastases had previously been
      reviewed by 2 neuroradiologists. Additional relevant clinical data were
      extracted. The influence of clinical and imaging characteristics on survival was
      assessed by Kaplan-Meier survival curves and log-rank tests for categoric
      characteristics. RESULTS: Forty-nine patients had 70 intramedullary spinal cord
      metastases; 10 (20%) of these patients had multiple metastases. From the date of
      diagnosis, median survival for all patients was 104 days (95% CI, 48-156 days).
      One clinical feature was associated with decreased median survival: lung or
      breast primary malignancy (57 days) compared with all other malignancy types (308
      days; P < .001). Three MR imaging features were associated with decreased median
      survival: multiple intramedullary spinal cord metastases (53 versus 121 days, P =
      .022), greater longitudinal extent of cord T2 hyperintensity (if >=3 segments,
      111 days; if <=2, 184 days; P = .018), and ancillary visualization of the primary
      tumor and/or non-CNS metastases (96 versus 316 days, P = .012). CONCLUSIONS:
      Spinal cord edema spanning multiple segments, the presence of multifocal
      intramedullary spinal cord metastases, and ancillary evidence for non-CNS
      metastases and/or the primary tumor are MR imaging features associated with
      decreased survival and should be specifically sought. Patients with either a lung
      or breast primary malignancy are expected to have decreased survival compared
      with other primary tumor types.

PMID- 25395658
TI  - Attenuation of blood flow pulsatility along the Atlas slope: a physiologic
      property of the distal vertebral artery?
AB  - BACKGROUND AND PURPOSE: Physiologic and pathologic arterial tortuosity may
      attenuate blood flow pulsatility. The aim of this prospective study was to assess
      a potential effect of the curved V3 segment (Atlas slope) of the vertebral artery
      on arterial flow pulsatility. The pulsatility index and resistance index were
      used to assess blood flow pulsatility. MATERIALS AND METHODS: Twenty-one healthy
      volunteers (17 men, 4 women; mean age, 32 years) were examined with a 3T MR
      imaging system. Blood velocities were measured at 2 locations below (I and II)
      and at 1 location above the V3 segment (III) of the vertebral artery by using a
      high-resolution 2D-phase-contrast sequence with multidirectional velocity
      encoding. RESULTS: Pulsatility and resistance indices decreased along all
      measurement locations from proximal to distal. The pulsatility index decreased
      significantly from location II to III and from I to II. However, the decrease was
      more pronounced along the Atlas slope than in the straight-vessel section below.
      The decrease of the resistance index was highly significant along the Atlas slope
      (location II to III). The decrease from location I to II was small and not
      significant. CONCLUSIONS: The pronounced decrease in pulsatility and resistance
      indices along the interindividually uniformly bent V3 segment compared with a
      straight segment of the vertebral artery indicates a physiologic attenuating
      effect of the Atlas slope on arterial flow pulsatility. A similar effect has been
      described for the carotid siphon. A physiologic reduction of pulsatility in brain
      supplying arteries would be in accordance with several recent publications
      reporting a correlation of increased arterial flow pulsatility with
      leukoencephalopathy and lacunar stroke.

PMID- 25395657
TI  - Percutaneous injection of radiopaque gelified ethanol for the treatment of lumbar
      and cervical intervertebral disk herniations: experience and clinical outcome in
      80 patients.
AB  - BACKGROUND AND PURPOSE: Chemonucleolysis represents a minimally invasive
      percutaneous technique characterized by an intradiskal injection of materials
      under fluoroscopic or CT guidance. Recently, a substance based on radiopaque
      gelified ethanol has been introduced. The purpose of this study was to describe
      the indications, procedure, safety, and efficacy of radiopaque gelified ethanol
      in the percutaneous treatment of cervical and lumbar disk herniations. MATERIALS
      AND METHODS: Between September 2010 and August 2013, 80 patients (32 women and 48
      men; age range, 18-75 years) were treated for 107 lumbar disk herniations (L2-L3,
      n = 1; L3-L4, n = 15; L4-L5, n = 53; and L5-S1, n = 38) and 9 cervical disk
      herniations (C4-C5, n = 2; C5-C6, n = 2; C6-C7, n = 3; and C7-D1, n = 2) by
      percutaneous intradiskal injection of radiopaque gelified ethanol under
      fluoroscopic guidance. Thirty-six patients underwent a simultaneous treatment of
      2 disk herniations. Patient symptoms were resistant to conservative therapy, with
      little or no pain relief after 4-6 weeks of physical therapy and drugs. All
      patients were evaluated by the Visual Analog Scale and the Oswestry Disability
      Index. RESULTS: Sixty-two of 73 (85%) patients with lumbar disk herniations and
      6/7 (83%) patients with cervical disk herniations obtained significant symptom
      improvement, with a Visual Analog Scale reduction of at least 4 points and an
      Oswestry Disability Index reduction of at least 40%. Leakage of radiopaque
      gelified ethanol in the surrounding tissues occurred in 19 patients, however
      without any clinical side effects. CONCLUSIONS: In our experience, percutaneous
      intradiskal injection of radiopaque gelified ethanol is safe and effective in
      reducing the period of recovery from disabling symptoms.

PMID- 25395660
TI  - Coffee houses and reading rooms.

PMID- 25395659
TI  - Small pipes: preliminary experience with 3-mm or smaller pipeline flow-diverting
      stents for aneurysm repair prior to regulatory approval.
AB  - Flow diversion has become an established treatment option for challenging
      intracranial aneurysms. The use of small devices of <=3-mm diameter remains
      unapproved by major regulatory bodies. A retrospective review of patients treated
      with Pipeline Embolization Devices of <=3-mm diameter at 3 Canadian institutions
      was conducted. Clinical and radiologic follow-up data were collected and
      reported. Twelve cases were treated with >=1 Pipeline Embolization Device of <=3
      mm diameter, including 2 with adjunctive coiling, with a median follow-up of 18
      months (range, 4-42 months). One patient experienced a posttreatment minor
      complication (8%) due to an embolic infarct. No posttreatment hemorrhage or
      delayed complications such as in-stent stenosis/thrombosis were observed.
      Radiologic occlusion was seen in 9/12 cases (75%) and near-occlusion in 2/12
      cases (17%). Intracranial aneurysm treatment with small-diameter flow-diverting
      stents provided safe and effective aneurysm closure in this small selected
      sample. These devices should be further studied and considered for regulatory
      approval. 

PMID- 25395661
TI  - Time-resolved contrast-enhanced MR angiography of spinal vascular malformations.
AB  - BACKGROUND AND PURPOSE: The diagnosis of spinal vascular malformations may be
      challenging on conventional MR imaging because neither the location of the signal
      abnormality in the spinal cord nor the level of the abnormal flow voids
      correlates with the level of the fistula. We conducted a retrospective evaluation
      of the utility of using a time-resolved imaging of contrast kinetics sequence in
      the diagnosis, characterization, and localization of spinal vascular
      malformations, comparing it with the criterion standard of spinal DSA. MATERIALS
      AND METHODS: Fifty-five consecutive patients with a suspected diagnosis of spinal
      vascular malformation underwent time-resolved imaging of contrast kinetics
      followed by spinal DSA. All scans were performed on a 1.5T scanner by using a
      standard 8-channel spine coil and were reported by a neuroradiologist before the
      DSA was performed. RESULTS: Forty-seven lesions were confirmed on time-resolved
      imaging of contrast kinetics and classified as spinal dural arteriovenous
      fistulas (n = 33, with 1 patient having a type Ib fistula), perimedullary spinal
      cord arteriovenous fistulas (n = 10), and intramedullary arteriovenous
      malformations (n = 3). One patient had an extradural spinal vascular
      malformation. Time-resolved imaging of contrast kinetics identified the location
      of the arterial feeder to within 1 vertebral level in 27/33 patients (81.8%) with
      spinal dural arteriovenous fistulas and correctly predicted the side in 22/33
      (66.6%) patients. Perimedullary spinal cord arteriovenous fistulas were
      erroneously considered to represent spinal dural arteriovenous fistulas before
      spinal DSA. The anatomy of the arterial supply to intramedullary arteriovenous
      malformations was also poorly characterized on time-resolved contrast-enhanced MR
      angiography. CONCLUSIONS: It has been our experience that time-resolved imaging
      of contrast kinetics is a useful confirmatory tool when a spinal vascular
      malformation is suspected on the basis of clinical and conventional MR imaging
      findings. As experience with the technique grows and sequences are refined, it
      may be possible to rely on time-resolved imaging of contrast kinetics as a
      screening tool for the diagnosis of spinal vascular malformations.

PMID- 25395662
TI  - Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal
      tumorigenesis.
AB  - Down-regulation of miR-26 family members has been implicated in the pathogenesis
      of multiple malignancies. In some settings, including glioma, however, miR-26
      mediated repression of PTEN promotes tumorigenesis. To investigate the contexts
      in which the tumor suppressor versus oncogenic activity of miR-26 predominates in
      vivo, we generated miR-26a transgenic mice. Despite measureable repression of
      Pten, elevated miR-26a levels were not associated with malignancy in transgenic
      animals. We documented reduced miR-26 expression in human colorectal cancer and,
      accordingly, showed that miR-26a expression potently suppressed intestinal
      adenoma formation in Apc(min/+) mice, a model known to be sensitive to Pten
      dosage. These studies reveal a tumor suppressor role for miR-26 in intestinal
      cancer that overrides putative oncogenic activity, highlighting the therapeutic
      potential of miR-26 delivery to this tumor type. 

PMID- 25395663
TI  - Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell
      production.
AB  - Identifying signaling pathways that regulate hematopoietic stem and progenitor
      cell (HSPC) formation in the embryo will guide efforts to produce and expand
      HSPCs ex vivo. Here we show that sterile tonic inflammatory signaling regulates
      embryonic HSPC formation. Expression profiling of progenitors with lymphoid
      potential and hematopoietic stem cells (HSCs) from aorta/gonad/mesonephros (AGM)
      regions of midgestation mouse embryos revealed a robust innate
      immune/inflammatory signature. Mouse embryos lacking interferon gamma (IFN-gamma)
      or IFN-alpha signaling and zebrafish morphants lacking IFN-gamma and IFN-phi
      activity had significantly fewer AGM HSPCs. Conversely, knockdown of IFN
      regulatory factor 2 (IRF2), a negative regulator of IFN signaling, increased
      expression of IFN target genes and HSPC production in zebrafish. Chromatin
      immunoprecipitation (ChIP) combined with sequencing (ChIP-seq) and expression
      analyses demonstrated that IRF2-occupied genes identified in human fetal liver
      CD34(+) HSPCs are actively transcribed in human and mouse HSPCs. Furthermore, we
      demonstrate that the primitive myeloid population contributes to the local
      inflammatory response to impact the scale of HSPC production in the AGM region.
      Thus, sterile inflammatory signaling is an evolutionarily conserved pathway
      regulating the production of HSPCs during embryonic development. 

PMID- 25395665
TI  - The impact of macroscopic epistasis on long-term evolutionary dynamics.
AB  - Genetic interactions can strongly influence the fitness effects of individual
      mutations, yet the impact of these epistatic interactions on evolutionary
      dynamics remains poorly understood. Here we investigate the evolutionary role of
      epistasis over 50,000 generations in a well-studied laboratory evolution
      experiment in Escherichia coli. The extensive duration of this experiment
      provides a unique window into the effects of epistasis during long-term
      adaptation to a constant environment. Guided by analytical results in the weak
      mutation limit, we develop a computational framework to assess the compatibility
      of a given epistatic model with the observed patterns of fitness gain and
      mutation accumulation through time. We find that a decelerating fitness
      trajectory alone provides little power to distinguish between competing models,
      including those that lack any direct epistatic interactions between mutations.
      However, when combined with the mutation trajectory, these observables place
      strong constraints on the set of possible models of epistasis, ruling out many
      existing explanations of the data. Instead, we find that the data are consistent
      with a "two-epoch" model of adaptation, in which an initial burst of diminishing
      returns epistasis is followed by a steady accumulation of mutations under a
      constant distribution of fitness effects. Our results highlight the need for
      additional DNA sequencing of these populations, as well as for more sophisticated
      models of epistasis that are compatible with all of the experimental data. 

PMID- 25395666
TI  - A novel role for the zinc-finger transcription factor EGL-46 in the
      differentiation of gas-sensing neurons in Caenorhabditis elegans.
AB  - Oxygen (O2) and carbon dioxide (CO2) provoke distinct olfactory behaviors via
      specialized sensory neurons across metazoa. In the nematode C. elegans, the BAG
      sensory neurons are specialized to sense changes in both O2 and CO2 levels in the
      environment. The precise functionality of these neurons is specified by the
      coexpression of a membrane-bound receptor-type guanylyl cyclase GCY-9 that is
      required for responses to CO2 upshifts and the soluble guanylyl cyclases GCY-31
      and GCY-33 that mediate responses to downshifts in O2. Expression of these gas
      sensing molecules in the BAG neurons is partially, although not completely,
      controlled by ETS-5, an ETS-domain-containing transcription factor, and EGL-13, a
      Sox transcription factor. We report here the identification of EGL-46, a zinc
      finger transcription factor, which regulates BAG gas-sensing fate in partially
      parallel pathways to ETS-5 and EGL-13. Thereby, three conserved transcription
      factors collaborate to ensure neuron type-specific identity features of the BAG
      gas-sensing neurons. 

PMID- 25395664
TI  - Signaling by the engulfment receptor draper: a screen in Drosophila melanogaster
      implicates cytoskeletal regulators, Jun N-terminal Kinase, and Yorkie.
AB  - Draper, the Drosophila melanogaster homolog of the Ced-1 protein of
      Caenorhabditis elegans, is a cell-surface receptor required for the recognition
      and engulfment of apoptotic cells, glial clearance of axon fragments and
      dendritic pruning, and salivary gland autophagy. To further elucidate mechanisms
      of Draper signaling, we screened chromosomal deficiencies to identify loci that
      dominantly modify the phenotype of overexpression of Draper isoform II
      (suppressed differentiation of the posterior crossvein in the wing). We found
      evidence for 43 genetic modifiers of Draper II. Twenty-four of the 37 suppressor
      loci and 3 of the 6 enhancer loci were identified. An additional 5 suppressors
      and 2 enhancers were identified among mutations in functionally related genes.
      These studies reveal positive contributions to Drpr signaling for the Jun N
      terminal Kinase pathway, supported by genetic interactions with hemipterous,
      basket, jun, and puckered, and for cytoskeleton regulation as indicated by
      genetic interactions with rac1, rac2, RhoA, myoblast city, Wiskcott-Aldrich
      syndrome protein, and the formin CG32138, and for yorkie and expanded. These
      findings indicate that Jun N-terminal Kinase activation and cytoskeletal
      remodeling collaborate in Draper signaling. Relationships between Draper
      signaling and Decapentaplegic signaling, insulin signaling, Salvador/Warts/Hippo
      signaling, apical-basal cell polarity, and cellular responses to mechanical
      forces are also discussed. 

PMID- 25395667
TI  - TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell
      proliferation and network-formation.
AB  - Anandamide (N-arachidonyl ethanolamide, AEA) is an endogenous cannabinoid that is
      involved in various pathological conditions, including cardiovascular diseases
      and tumor-angiogenesis. Herein, we tested the involvement of classical
      cannabinoid receptors (CBRs) and the Ca(2+)-channel transient receptor potential
      vanilloid 1 (TRPV1) on cellular AEA uptake and its effect on endothelial cell
      proliferation and network-formation. Uptake of the fluorescence-labeled
      anandamide (SKM4-45-1) was monitored in human endothelial colony-forming cells
      (ECFCs) and a human endothelial-vein cell line (EA.hy926). Involvement of the
      receptors during AEA translocation was determined by selective pharmacological
      inhibition (AM251, SR144528, CID16020046, SB366791) and molecular interference by
      TRPV1-selective siRNA-mediated knock-down and TRPV1 overexpression. We show that
      exclusively TRPV1 contributes essentially to AEA transport into endothelial cells
      in a Ca(2+)-independent manner. This TRPV1 function is a prerequisite for AEA
      induced endothelial cell proliferation and network-formation. Our findings point
      to a so far unknown moonlighting function of TRPV1 as Ca(2+)-independent
      contributor/regulator of AEA uptake. We propose TRPV1 as representing a promising
      target for development of pharmacological therapies against AEA-triggered
      endothelial cell functions, including their stimulatory effect on tumor
      angiogenesis. 

PMID- 25395668
TI  - ATRX is required for maintenance of the neuroprogenitor cell pool in the
      embryonic mouse brain.
AB  - Mutations in the alpha-thalassemia mental retardation X-linked (ATRX) gene cause
      a spectrum of abnormalities including intellectual disability, developmental
      delay, seizures, and microcephaly. The ATRX protein is highly enriched at
      heterochromatic repetitive sequences adjacent to the centromere, and ATRX
      depletion results in chromosome congression, segregation, and cohesion defects.
      Here, we show that Cre-mediated inactivation of Atrx in the embryonic mouse (Mus
      musculus) brain results in expansion of cerebral cortical layer VI, and a
      concurrent thinning of layers II-IV. We observed increased cell cycle exit during
      early-mid neurogenesis, and a depletion of apical progenitors by late
      neurogenesis in the Atrx-null neocortex, explaining the disproportionate
      layering. Premature differentiation was associated with an increased generation
      of outer radial glia (oRG) and TBR2-expressing basal progenitors, as well as
      increased generation of early-born post-mitotic projection neurons. Atrx deletion
      also reduced the fidelity of mitotic spindle orientation in apical progenitors,
      where mutant cells were often oriented at non-parallel angles of division
      relative to the ventricular surface. We conclude that ATRX is required for
      correct lamination of the mouse neocortex by regulating the timing of
      neuroprogenitor cell differentiation. 

PMID- 25395669
TI  - Genetic interaction implicates iRhom2 in the regulation of EGF receptor
      signalling in mice.
AB  - iRhoms are closely related to rhomboid intramembrane proteases but lack catalytic
      activity. In mammals iRhoms are known to regulate the trafficking of TACE, the
      protease that cleaves the membrane bound inflammatory cytokine TNF. We have
      mapped a spontaneously occurring mouse mutation with a loss of hair phenotype,
      curly bare (cub), to the Rhbdf2 locus, which encodes the iRhom2 protein. The cub
      deletion removes the first 268 amino acids of the iRhom2 protein but is not a
      loss of function. We have also identified a previously reported suppressor of
      cub, called Mcub (modifier of curly bare), and find it to be a loss of function
      allele of the amphiregulin gene (Areg). Amphiregulin is an activating ligand of
      the epidermal growth factor receptor (EGFR) that, like TNF, is released by TACE.
      Our results therefore imply a regulatory link between iRhoms and EGFR signalling
      in mammals. We have tested the model that the cub mutation leads to iRhom2
      hyperactivity and consequently excess TACE processing of amphiregulin and
      elevated EGFR signalling. Our results do not support this hypothesis: we find
      that, compared to wild-type cells, cub mutant embryonic fibroblasts release less
      amphiregulin, and that the cub mutant form of iRhom2 is less able than wild type
      to bind to TACE and promote its maturation. 

PMID- 25395670
TI  - Pre-metazoan origins and evolution of the cadherin adhesome.
AB  - Vertebrate adherens junctions mediate cell-cell adhesion via a "classical"
      cadherin-catenin "core" complex, which is associated with and regulated by a
      functional network of proteins, collectively named the cadherin adhesome
      ("cadhesome"). The most basal metazoans have been shown to conserve the cadherin
      catenin "core", but little is known about the evolution of the cadhesome. Using a
      bioinformatics approach based on both sequence and structural analysis, we have
      traced the evolution of this larger network in 26 organisms, from the uni
      cellular ancestors of metazoans, through basal metazoans, to vertebrates.
      Surprisingly, we show that approximately 70% of the cadhesome, including proteins
      with similarity to the catenins, predate metazoans. We found that the transition
      to multicellularity was accompanied by the appearance of a small number of
      adaptor proteins, and we show how these proteins may have helped to integrate pre
      metazoan sub-networks via PDZ domain-peptide interactions. Finally, we found the
      increase in network complexity in higher metazoans to have been driven primarily
      by expansion of paralogs. In summary, our analysis helps to explain how the
      complex protein network associated with cadherin at adherens junctions first came
      together in the first metazoan and how it evolved into the even more complex
      mammalian cadhesome. 

PMID- 25395671
TI  - CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk
      glycosylation and the membrane domain.
AB  - The multi-domain CX3CL1 transmembrane chemokine triggers leukocyte adherence
      without rolling and migration by presenting its chemokine domain (CD) to its
      receptor CX3CR1. Through the combination of functional adhesion assays with
      structural analysis using FRAP, we investigated the functional role of the other
      domains of CX3CL1, i.e., its mucin stalk, transmembrane domain, and cytosolic
      domain. Our results indicate that the CX3CL1 molecular structure is finely
      adapted to capture CX3CR1 in circulating cells and that each domain has a
      specific purpose: the mucin stalk is stiffened by its high glycosylation to
      present the CD away from the membrane, the transmembrane domain generates the
      permanent aggregation of an adequate amount of monomers to guarantee adhesion and
      prevent rolling, and the cytosolic domain ensures adhesive robustness by
      interacting with the cytoskeleton. We propose a model in which quasi-immobile
      CX3CL1 bundles are organized to quickly generate adhesive patches with
      sufficiently high strength to capture CX3CR1+ leukocytes but with sufficiently
      low strength to allow their patrolling behavior. 

PMID- 25395673
TI  - MicroRNA-26b functions as a proapoptotic factor in porcine follicular Granulosa
      cells by targeting Sma-and Mad-related protein 4.
AB  - Sma- and Mad-related protein 4 (SMAD4) is the central mediator of the
      transforming growth factor beta signaling pathway and is closely related to
      mammalian reproductive ability and the development of ovarian follicles. However,
      little is currently known about the role of SMAD4 in mammalian follicular
      granulosa cell (GC) apoptosis or its regulation by miRNAs. Here, we found that
      the porcine SMAD4 protein was expressed at high levels in GCs and oocytes from
      primary, preantral, and antral follicles, and only slightly expressed in theca
      cells; its expression level was down-regulated in apoptotic ovarian GCs,
      suggesting that SMAD4 may be involved in ovary development and selection.
      Overexpression and knockdown of SMAD4 increased the proliferation and apoptosis
      of cultured porcine GCs, respectively. In addition, the use of miRNA mimics and
      luciferase reporter assays revealed that miRNA-26b (miR-26b) functions as a
      proapoptotic factor in porcine follicular GCs by targeting the 3'-untranslated
      region of the SMAD4 gene. Overexpression of miR-26b in follicular GCs suppressed
      SMAD4 mRNA and protein levels, resulting in down-regulation of the antiapoptotic
      BCL-2 gene and the promotion of GC apoptosis. Furthermore, transforming growth
      factor beta 1 (TGF-beta1) down-regulates miR-26b expression in porcine GCs. Taken
      together, these data suggest that SMAD4 plays a critical role in porcine
      follicular GC apoptosis and follicular atresia and that miR-26b may have a
      proapoptotic role in GCs by regulating the expression of SMAD4 in the
      transforming growth factor beta signaling pathway. 

PMID- 25395674
TI  - High-throughput sequencing analyses of XX genital ridges lacking FOXL2 reveal
      DMRT1 up-regulation before SOX9 expression during the sex-reversal process in
      goats.
AB  - FOXL2 loss of function in goats leads to the early transdifferentiation of
      ovaries into testes, then to the full sex reversal of XX homozygous mutants. By
      contrast, Foxl2 loss of function in mice induces an arrest of follicle formation
      after birth, followed by complete female sterility. In order to understand the
      molecular role of FOXL2 during ovarian differentiation in the goat species,
      putative FOXL2 target genes were determined at the earliest stage of gonadal sex
      specific differentiation by comparing the mRNA profiles of XX gonads expressing
      the FOXL2 protein or not. Of these 163 deregulated genes, around two-thirds
      corresponded to testicular genes that were up-regulated when FOXL2 was absent,
      and only 19 represented female-associated genes, down-regulated in the absence of
      FOXL2. FOXL2 should therefore be viewed as an antitestis gene rather than as a
      female-promoting gene. In particular, the key testis-determining gene DMRT1 was
      found to be up-regulated ahead of SOX9, thus suggesting in goats that SOX9
      primary up-regulation may require DMRT1. Overall, our results equated to FOXL2
      being an antitestis gene, allowing us to propose an alternative model for the sex
      determination process in goats that differs slightly from that demonstrated in
      mice. 

PMID- 25395675
TI  - Protection of murine spermatogenesis against ionizing radiation-induced
      testicular injury by a green tea polyphenol.
AB  - Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol in green tea, exerts
      antiapoptotic activity and prevents tissue damage against different stimuli.
      Herein, we investigated the effects of EGCG treatment to simultaneously improve
      spermatogenesis following ionizing radiation (IR) (at a dose of 2 Gy). Mice were
      intraperitoneally injected with 50 mg/kg EGCG or vehicle control 3 days prior to
      the irradiation, and the treatment lasted intermittently for 24 days. Supplement
      with exogenous EGCG protected against short-term germ cell loss and attenuated IR
      elicited testicular oxidative stress. Mechanistically, prosurvival effects of
      EGCG treatment upon IR stress were regulated, at least in part, via the mitogen
      activated protein kinase/BCL2 family/caspase 3 pathway. Consistently, at post-IR
      Day 21, histological analyses revealed tubule damage, desquamation of germ cells,
      and impairment of caudal parameters in irradiated testis, which could be
      significantly improved by intermittent EGCG treatment. In addition, long-term
      EGCG application ameliorated the IR-induced blood-testicular barrier permeability
      and suppressed testicular steroidogenesis, thus exerting a stimulatory effect on
      the spermatogenic recovery. Collectively, EGCG appeared to efficiently prevent
      germ cells from radiation-induced cell death via multiple mechanisms. Employment
      of this bioactive polyphenol should be an attractive strategy to preserve
      fertility in males exposed to conventional radiation therapy and warrants further
      investigation.

PMID- 25395676
TI  - Seminal vesicle secretion 2 acts as a protectant of sperm sterols and prevents
      ectopic sperm capacitation in mice.
AB  - Seminal vesicle secretion 2 (SVS2) is a protein secreted by the mouse seminal
      vesicle. We previously demonstrated that SVS2 regulates fertilization in mice;
      SVS2 is attached to a ganglioside GM1 on the plasma membrane of the sperm head
      and inhibits sperm capacitation in in vitro fertilization as a decapacitation
      factor. Furthermore, male mice lacking SVS2 display prominently reduced fertility
      in vivo, which indicates that SVS2 protects spermatozoa from some spermicidal
      attack in the uterus. In this study, we tried to investigate the mechanisms by
      which SVS2 controls in vivo sperm capacitation. SVS2-deficient males that mated
      with wild-type partners resulted in decreased cholesterol levels on ejaculated
      sperm in the uterine cavity. SVS2 prevented cholesterol efflux from the sperm
      plasma membrane and incorporated liberated cholesterol in the sperm plasma
      membrane, thereby reversibly preventing the induction of sperm capacitation by
      bovine serum albumin and methyl-beta-cyclodextrin in vitro. SVS2 enters the
      uterus and the uterotubal junction, arresting sperm capacitation in this area.
      Therefore, our results show that SVS2 keeps sterols on the sperm plasma membrane
      and plays a key role in unlocking sperm capacitation in vivo. 

PMID- 25395677
TI  - DAX1/NR0B1 was expressed during mammalian gonadal development and gametogenesis
      before it was recruited to the eutherian X chromosome.
AB  - The nuclear receptor subfamily 0, group B, member 1 (NR0B1) gene is an orphan
      nuclear receptor that is X-linked in eutherian mammals and plays a critical role
      in the establishment and function of the hypothalamic-pituitary-adrenal-gonadal
      axis. Duplication or overexpression of NR0B1 in eutherian males causes male to
      female sex reversal, and mutation and deletions of NR0B1 cause testicular
      defects. Thus, gene dosage is critical for the function of NR0B1 in normal
      gonadogenesis. However, NR0B1 is autosomal in all noneutherian vertebrates,
      including marsupials and monotreme mammals, and two active copies of the gene are
      compatible with both male and female gonadal development. In the current study,
      we examined the evolution and expression of autosomal NR0B1 during gonadal
      development in a marsupial (the tammar wallaby) as compared to the role of its X
      linked orthologues in a eutherian (the mouse). We show that NR0B1 underwent rapid
      evolutionary change when it relocated from its autosomal position in the
      nonmammalian vertebrates, monotremes, and marsupials to an X-linked location in
      eutherian mammals. Despite the acquisition of a novel genomic location and a
      unique N-terminal domain, NR0B1 protein distribution was remarkably similar
      between mice and marsupials both throughout gonadal development and during gamete
      formation. A conserved accumulation of NR0B1 protein was observed in developing
      oocytes, where its function appears to be critical in the early embryo, prior to
      zygotic genome activation. Together these findings suggest that NR0B1 had a
      conserved role in gonadogenesis that existed long before it moved to the X
      chromosome and despite undergoing significant evolutionary change.

PMID- 25395678
TI  - A leucine-rich diet modulates the tumor-induced down-regulation of the MAPK/ERK
      and PI3K/Akt/mTOR signaling pathways and maintains the expression of the
      ubiquitin-proteasome pathway in the placental tissue of NMRI mice.
AB  - Placental tissue injury is concomitant with tumor development. We investigated
      tumor-driven placental damage by tracing certain steps of the protein synthesis
      and degradation pathways under leucine-rich diet supplementation in MAC16 tumor
      bearing mice. Cell signaling and ubiquitin-proteasome pathways were assessed in
      the placental tissues of pregnant mice, which were distributed into three groups
      on a control diet (pregnant control, tumor-bearing pregnant, and pregnant
      injected with MAC-ascitic fluid) and three other groups on a leucine-rich diet
      (pregnant, tumor-bearing pregnant, and pregnant injected with MAC-ascitic fluid).
      MAC tumor growth down-regulated the cell-signaling pathways of the placental
      tissue and decreased the levels of IRS-1, Akt/PKB, Erk/MAPK, mTOR, p70S6K, STAT3,
      and STAT6 phosphorylated proteins, as assessed by the multiplex Millipore Luminex
      assay. Leucine supplementation maintained the levels of these proteins within the
      established cell-signaling pathways. In the tumor-bearing group (MAC) only, the
      placental tissue showed increased PC5 mRNA expression, as assessed by
      quantitative RT-PCR, decreased 19S and 20S protein expression, as assessed by
      Western blot analysis, and decreased placental tyrosine levels, likely reflecting
      up-regulation of the ubiquitin-proteasome pathway. Similar effects were found in
      the pregnant injected with MAC-ascitic fluid group, confirming that the effects
      of the tumor were mimicked by MAC-ascitic fluid injection. Although tumor
      progression occurred, the degradation pathway-related protein levels were
      modulated under leucine-supplementation conditions. In conclusion, tumor
      evolution reduced the protein expression of the cell-signaling pathway associated
      with elevated protein degradation, thereby jeopardizing placental activity. Under
      the leucine-rich diet, the impact of cancer on placental function could be
      minimized by improving the cell-signaling activity and reducing the proteolytic
      process. 

PMID- 25395680
TI  - Maternal citrulline supplementation prevents prenatal N(G)-nitro-L-arginine
      methyl ester (L-NAME)-induced programmed hypertension in rats.
AB  - Nitric oxide (NO) deficiency induced by the NO synthase (NOS) inhibitor N(G)
      nitro-L-arginine-methyl ester (L-NAME) resulted in hypertension. L-citrulline
      (CIT) can be converted to L-arginine to generate NO. We examined whether maternal
      CIT supplementation can prevent L-NAME-induced programmed hypertension. Pregnant
      Sprague-Dawley rats were assigned to four groups: control, L-NAME, control +
      citrulline (CIT), and L-NAME + citrulline (L-NAME+CIT). Pregnant rats received L
      NAME administration at 60 mg/kg/day subcutaneously during pregnancy alone or with
      additional 0.25% l-citrulline solution in drinking water during the whole period
      of pregnancy and lactation. Male offspring were sacrificed at 12 wk of age. L
      NAME exposure during pregnancy induces hypertension in the 12-wk-old offspring.
      Maternal CIT therapy prevented L-NAME-induced programmed hypertension, which was
      associated with a decreased asymmetric dimethylarginine (ADMA) concentration and
      an increased L-arginine-to-ADMA ratio in the kidney, increased urinary cGMP
      levels, and decreased renal protein levels of type 3 sodium hydrogen exchanger
      (NHE3). Together, our data suggest that the beneficial effects of CIT
      supplementation are attributed to its ability to increase NO level in the kidney
      and inhibition of NHE3 expression. Our results suggest that supplementing CIT in
      pregnant women with NO deficiency can improve fetal development and prevent
      programmed hypertension.

PMID- 25395681
TI  - Adrenomedullin2 (ADM2)/intermedin (IMD) in rat ovary: changes in estrous cycle
      and pregnancy and its role in ovulation and steroidogenesis.
AB  - Adrenomedullin2 (ADM2) is reported to facilitate embryo implantation and
      placental development. Therefore, the current study was undertaken to identify if
      ADM2 has a functional role in ovary to facilitate its reproductive actions. This
      study shows that the expression of ADM2 is differentially regulated in rat
      estrous cycle and that ADM2 increases the synthesis and secretion of 17beta
      estradiol accompanied with an increase in the expression of steroidogenic factor
      1 (Sf1), estrogen receptor Esr1, and enzymes involved in steroidogenesis in
      equine chorionic gonadotropin (eCG)-treated rat ovaries. In addition, inhibition
      of endogenous ADM2 function in eCG-treated immature rats caused impaired
      ovulation. Furthermore, the mRNA expression of Adm2 and receptor activity
      modifying protein 3 is higher in the ovary on Day 18 compared to nonpregnant and
      pregnant rats on Day 22. ADM2-like immunoreactivity is localized in granulosa
      cells, blood vessels, oocytes, cumulous oophorus, and corpus luteum of pregnant
      ovaries, suggesting a potential role for ADM2 in the ovary. This is supported by
      the presence of ADM2-like immunoreactivity in the corpus luteum during pregnancy
      and a decline in aromatase immunoreactivity in corpus luteum on Day 9 of
      gestation in rats infused with ADM2 antagonist during implantation and
      decidualization phase. Taken together, this study suggests a potential
      involvement of ADM2 in the rat ovary in regulating synthesis of estradiol to
      support ovulation and facilitate efficient implantation and placental development
      for a successful pregnancy. 

PMID- 25395682
TI  - Hemoglobin: a gas transport molecule that is hormonally regulated in the ovarian
      follicle in mice and humans.
AB  - An increasing number of nonerythroid tissues are found to express hemoglobin mRNA
      and protein. Hemoglobin is a well-described gas transport molecule, especially
      for O2, but also for NO, CO2, and CO, and also acts as a reactive oxygen species
      scavenger. We previously found Hba-a1 and Hbb mRNA and protein at high levels
      within mouse periovulatory cumulus cells, but not in cumulus following in vitro
      maturation. This led us to investigate the temporal and spatial regulation in
      follicular cells during the periovulatory period. Cumulus-oocyte complexes were
      collected from equine chorionic gonadotropin/human chorionic gonadotropin-treated
      peripubertal SV129 female mice and collected and analyzed for gene expression and
      protein localization at a variety of time points over the periovulatory period. A
      further cohort matured in vitro with different forms of hemoglobin (ferro- and
      ferrihemoglobin) under different O2 atmospheric conditions (2%, 5%, and 20% O2)
      were subsequently fertilized in vitro and cultured to the blastocyst stage.
      Murine mRNA transcripts for hemoglobin were regulated by stimulation of the
      ovulatory cascade, in both granulosa and cumulus cells, and expression of HBA1
      and HBB was highly significant in human granulosa and cumulus, but erythrocyte
      cell marker genes were not. Several other genes involved in hemoglobin function
      were similarly luteinizing hormone-regulated, including genes for heme
      biosynthesis. Immunohistochemistry revealed a changing localization pattern of
      HBA-A1 protein in murine cumulus cells and oocytes following the ovulatory
      signal. Significantly, no positive staining for HBA-A1 protein was observed
      within in vitro-matured oocytes, but, if coincubated with ferro- or
      ferrihemoglobin, cytoplasmic HBA-A1 was observed, similar to in vivo-derived
      oocytes. Addition of ferro-, but not ferrihemoglobin, had a small, positive
      effect on blastocyst yield, but only under either 2% or 20% O2 gas atmosphere.
      The identification of hemoglobin within granulosa and cumulus cells poses many
      questions as to its function in these cells. There are several possible roles,
      the most likely of which is either an O2 or NO sequestering molecule; perhaps
      both roles are engaged. The strong endocrine regulation during the periovulatory
      period suggests to us that one potential function of hemoglobin is to provide a
      short-lived hypoxic environment by binding very tightly any available O2. This,
      in turn, facilitates the differentiation of the follicle towards corpus luteum
      formation by enabling the stabilization of a key transcription factor known to
      initiate such differentiation: hypoxia inducible factor.

PMID- 25395683
TI  - Sensitivity analyses for parametric causal mediation effect estimation.
AB  - Causal mediation analysis uses a potential outcomes framework to estimate the
      direct effect of an exposure on an outcome and its indirect effect through an
      intermediate variable (or mediator). Causal interpretations of these effects
      typically rely on sequential ignorability. Because this assumption is not
      empirically testable, it is important to conduct sensitivity analyses.
      Sensitivity analyses so far offered for this situation have either focused on the
      case where the outcome follows a linear model or involve nonparametric or
      semiparametric models. We propose alternative approaches that are suitable for
      responses following generalized linear models. The first approach uses a Gaussian
      copula model involving latent versions of the mediator and the final outcome. The
      second approach uses a so-called hybrid causal-observational model that extends
      the association model for the final outcome, providing a novel sensitivity
      parameter. These models, while still assuming a randomized exposure, allow for
      unobserved (as well as observed) mediator-outcome confounders that are not
      affected by exposure. The methods are applied to data from a study of the effect
      of mother education on dental caries in adolescence. 

PMID- 25395684
TI  - Prevalence of corneal diseases in the rural Indian population: the Corneal
      Opacity Rural Epidemiological (CORE) study.
AB  - OBJECTIVE: The present population-based study was undertaken to estimate the
      prevalence, determinants and causes of corneal morbidity and blindness in a rural
      North Indian population. DESIGN: Population-based study in India with 12 899
      participants of all ages. METHODS: Participants were recruited from 25 village
      clusters of district Gurgaon, Haryana, India using random cluster sampling
      strategy. All individuals were examined in detail with a portable slit lamp for
      evidence of any corneal disease during the door-to-door examination.
      Comprehensive ocular examination including logMar visual acuity, slit lamp
      biomicroscopy, non-contact tonometry and dilated retinal evaluation was performed
      at a central clinic site in the respective villages. RESULTS: Overall, 12 113 of
      12 899 people (93.9% response rate) were examined during the household visits.
      Prevalence of corneal disease was 3.7% (95% CI 3.4% to 4.1%) and that of corneal
      blindness was 0.12% (95% CI 0.05% to 0.17%). Multivariable analysis demonstrated
      that corneal disease was significantly higher in the elderly (p<0.0001) and
      illiterates (p<0.0001). Common causes of corneal opacity in the study population
      were pterygium (34.5%), ocular trauma (22.3%) and infectious keratitis (14.9%).
      Corneal diseases contributing to blindness were post-surgical bullous keratopathy
      (46.2%) and corneal degenerations (23.1%). CONCLUSIONS: The study findings
      demonstrate that currently ocular trauma, infectious keratitis, post-surgical
      bullous keratopathy, and corneal degenerations are responsible for the major
      burden of corneal blindness and morbidity in the Indian population. The
      prevalence of corneal morbidity due to vitamin A deficiency and trachoma was low
      in this rural population.

PMID- 25395685
TI  - The development of infantile nystagmus.
AB  - PURPOSE: To obtain quantitative measurements of the development of infantile
      nystagmus in children. This task is challenging because the eye movement
      recording requires some cooperation. METHOD: The oscillations in short duration
      eye movement recordings were identified by the method of close returns and the
      characteristics of the saccadic main sequence were used to calibrate the
      oscillations. These techniques were applied to 11 subjects, aged 0-4 years, who
      were all tested on more than one occasion. RESULTS: The range of waveforms could
      be described by a sum of asymmetric pendular and pseudocycloid components. The
      amplitude of the nystagmus decreased from 0 to 1.5 years and then increased
      again. The foveation associated with the nystagmus increased up to 1.5 years and
      then remained approximately constant. The average visual acuity of the subjects
      increased steadily from 0 to 4 years. CONCLUSIONS: These findings imply that
      developmental waveform changes are associated with improved visual acuity but
      only until 1.5-2 years of age.

PMID- 25395686
TI  - Prediction of general hospital admission in people with dementia: cohort study.
AB  - BACKGROUND: People with dementia are extremely vulnerable in hospital and
      unscheduled admissions should be avoided if possible. AIMS: To identify any
      predictors of general hospital admission in people with dementia in a well
      characterised national prospective cohort study. METHOD: A cohort of 730 persons
      with dementia was drawn from the Scottish Dementia Research Interest Register
      (47.8% female; mean age 76.3 years, s.d. = 8.2, range 50-94), with a mean follow
      up period of 1.2 years. RESULTS: In the age- and gender-adjusted multivariable
      model (n = 681; 251 admitted), Neuropsychiatric Inventory score (hazard ratio per
      s.d. disadvantage 1.21, 95% CI 1.08-1.36) was identified as an independent
      predictor of admission to hospital. CONCLUSIONS: Neuropsychiatric symptoms in
      dementia, measured using the Neuropsychiatric Inventory, predict non-psychiatric
      hospital admission of people with dementia. Further studies are merited to test
      whether interventions to reduce such symptoms might reduce unscheduled admissions
      to acute hospitals.

PMID- 25395687
TI  - Postpartum change in common mental disorders among rural Vietnamese women:
      incidence, recovery and risk and protective factors.
AB  - BACKGROUND: In low- and middle-income countries little is known about changes in
      women's mental health status from the perinatal period to 15 months postpartum or
      the factors associated with different trajectories. AIMS: To determine the
      incidence and rates of recovery from common mental disorders (CMD) among rural
      Vietnamese women and the risk and protective factors associated with these
      outcomes from the perinatal period to 15 months after giving birth. METHOD: In a
      population-based prospective study, a systematically recruited cohort of women
      completed baseline assessments in either the last trimester of pregnancy or 4-6
      weeks after giving birth and were followed up 15 months later. The common mental
      disorders of major depression, generalised anxiety and panic disorder were
      assessed by psychiatrist-administered Structured Clinical Interview for DSM-IV
      Disorders at both baseline and follow-up. RESULTS: A total of 211 women provided
      complete data in this study. The incidence rate of CMD in the first postpartum
      year was 13% (95% CI 8-19), and 70% (95% CI 59-80) of women who had perinatal CMD
      recovered within the first postpartum year. Incidence was associated with having
      experienced childhood maltreatment, experiencing the intimate partner as
      providing little care, sensitivity, kindness or affection, and the chronic stress
      of household poverty. Recovery was associated with higher quality of a woman's
      relationships with her intimate partner and her own mother, longer period of
      mandated rest following birth, and sharing of domestic tasks and infant care.
      CONCLUSIONS: Modifiable social factors, in particular the quality of a woman's
      closest relationships with her partner and her own mother, and participation by
      family members in domestic work and infant care, are closely related to women's
      mental health in the first year after giving birth in resource-constrained
      settings.

PMID- 25395688
TI  - Intergenerational transmission of psychopathy and mediation via psychosocial risk
      factors.
AB  - BACKGROUND: Intergenerational continuities in criminal behaviour have been well
      documented, but the familial nature of psychopathic personality is less well
      understood. AIMS: To establish if there is an association between the
      psychopathic traits of a community sample of men and their offspring and whether
      psychosocial risk factors mediate this. METHOD: Participants of the Cambridge
      Study in Delinquent Development (n = 478 dyads) were assessed for psychopathy
      using the PCL: SV. Multilevel regression models were used to investigate
      intergenerational continuity and mediation models examined indirect effects.
      RESULTS: The fathers' psychopathy was transmitted to both sons and daughters. The
      transmission of Factor 1 scores was mediated via the fathers' employment
      problems. For male offspring, the Factor 2 scores were mediated via the fathers'
      drug use, accommodation and employment problems. For female offspring, Factor 2
      scores were mediated via the fathers' employment problems. CONCLUSIONS:
      Understanding of the specific role of certain psychosocial risk factors may be
      useful in developing preventive measures for the development of psychopathy.

PMID- 25395689
TI  - Droperidol v. haloperidol for sedation of aggressive behaviour in acute mental
      health: randomised controlled trial.
AB  - BACKGROUND: Agitation and aggression are significant problems in acute
      psychiatric units. There is little consensus on which drug is most effective and
      safest for sedation of these patients. AIMS: To compare the effectiveness and
      safety of haloperidol v. droperidol for patients with agitation and aggression.
      METHOD: In a masked, randomised controlled trial (ACTRN12611000565943)
      intramuscular droperidol (10 mg) was compared with intramuscular haloperidol (10
      mg) for adult patients with acute behavioural disturbance in a psychiatric
      intensive care unit. The primary outcome was time to sedation within 120 min.
      Secondary outcomes were use of additional sedation, adverse events and staff
      injuries. RESULTS: From 584 patients, 110 were randomised to haloperidol and 118
      to droperidol. Effective sedation occurred in 210 (92%) patients within 120 min.
      There was no significant difference in median time to sedation: 20 min
      (interquartile range 15-30, range 10-75) for haloperidol v. 25 min (IQR 15-30,
      range 10-115) for droperidol (P = 0.89). Additional sedation was used more often
      with haloperidol (13% v. 5%, P = 0.06), but adverse effects were less common with
      haloperidol (1% v. 5%, P = 0.12). There were 8 staff injuries. CONCLUSIONS: Both
      haloperidol and droperidol were effective for sedation of patients with acute
      behavioural disturbance.

PMID- 25395691
TI  - How Hispanic Patients Address Ambiguous versus Unambiguous Bias in the Doctor's
      Office.
AB  - Two studies examined Hispanic individuals' preferences for using ten different
      bias reduction strategies when interacting with a doctor whose beliefs about
      their group were either ambiguous or clearly biased. Consistent with predictions,
      participants who imagined interacting with a doctor whose beliefs were ambiguous
      preferred strategies that facilitate positive doctor-patient interactions,
      whereas participants whose doctor explicitly endorsed negative stereotypes about
      their group preferred strategies that address stereotype content. The results
      also revealed that, regardless of whether the doctor's beliefs were ambiguous or
      clearly biased, stigma consciousness predicted participants' preferences for
      using strategies that address stereotype content. These findings suggest that
      both doctors' behavior and individual-level factors influence how minority
      individuals choose to behave in a healthcare setting.

PMID- 25395690
TI  - Proportion of patients without mental disorders being treated in mental health
      services worldwide.
AB  - BACKGROUND: Previous research suggests that many people receiving mental health
      treatment do not meet criteria for a mental disorder but are rather 'the worried
      well'. AIMS: To examine the association of past-year mental health treatment with
      DSM-IV disorders. METHOD: The World Health Organization's World Mental Health
      (WMH) Surveys interviewed community samples of adults in 23 countries (n = 62
      305) about DSM-IV disorders and treatment in the past 12 months for problems with
      emotions, alcohol or drugs. RESULTS: Roughly half (52%) of people who received
      treatment met criteria for a past-year DSM-IV disorder, an additional 18% for a
      lifetime disorder and an additional 13% for other indicators of need (multiple
      subthreshold disorders, recent stressors or suicidal behaviours). Dose-response
      associations were found between number of indicators of need and treatment.
      CONCLUSIONS: The vast majority of treatment in the WMH countries goes to patients
      with mental disorders or other problems expected to benefit from treatment.

PMID- 25395692
TI  - Optimizing area under the ROC curve using semi-supervised learning.
AB  - Receiver operating characteristic (ROC) analysis is a standard methodology to
      evaluate the performance of a binary classification system. The area under the
      ROC curve (AUC) is a performance metric that summarizes how well a classifier
      separates two classes. Traditional AUC optimization techniques are supervised
      learning methods that utilize only labeled data (i.e., the true class is known
      for all data) to train the classifiers. In this work, inspired by semi-supervised
      and transductive learning, we propose two new AUC optimization algorithms hereby
      referred to as semi-supervised learning receiver operating characteristic
      (SSLROC) algorithms, which utilize unlabeled test samples in classifier training
      to maximize AUC. Unlabeled samples are incorporated into the AUC optimization
      process, and their ranking relationships to labeled positive and negative
      training samples are considered as optimization constraints. The introduced test
      samples will cause the learned decision boundary in a multidimensional feature
      space to adapt not only to the distribution of labeled training data, but also to
      the distribution of unlabeled test data. We formulate the semi-supervised AUC
      optimization problem as a semi-definite programming problem based on the margin
      maximization theory. The proposed methods SSLROC1 (1-norm) and SSLROC2 (2-norm)
      were evaluated using 34 (determined by power analysis) randomly selected datasets
      from the University of California, Irvine machine learning repository. Wilcoxon
      signed rank tests showed that the proposed methods achieved significant
      improvement compared with state-of-the-art methods. The proposed methods were
      also applied to a CT colonography dataset for colonic polyp classification and
      showed promising results.

PMID- 25395693
TI  - Pursuing Perfection: Distress and Interpersonal Functioning Among Adolescent Boys
      in Single-Sex and Co-Educational Independent Schools.
AB  - This study extends past findings of heightened problems among affluent youth by
      examining adjustment patterns among boys in two academically elite, independent
      high schools: one for boys only and the other coeducational. Both samples
      manifested disproportionately high rates of internalizing and externalizing
      symptoms, but only the co-educational boys showed elevations in substance use.
      Boys in both schools showed elevations in a new outcome domain examined:
      exhibitionistic narcissism. Multivariate analyses of predictors showed that
      parent criticism -- a defining feature of youths' maladaptive perfectionism --
      and perceived maternal depression emerged as major vulnerability factors for both
      samples in relation to symptom levels. On other parenting dimensions, boys in the
      single-sex school seemed to be particularly sensitive to feelings of alienation
      from their fathers and perceived paternal depression. Envy of peers'
      attractiveness was associated with adolescent distress in both samples, but
      appeared to be especially critical for co-educational boys. Results are
      discussed, focusing on the costs and benefits of boys' attendance at a single-sex
      versus co-educational school, along with implications for practice and future
      research.

PMID- 25395694
TI  - Synthesis and cell phototoxicity of a triply bridged fused diporphyrin appended
      with six thioglucose units.
AB  - A triply bridged fused diporphyrin appended with six thioglucose units is
      reported. This new, chemically and photochemically stable amphiphilic compound is
      taken up by breast cancer cells and causes cell death upon light exposure.
      Photophysical studies reveal absorption bands in the near IR region, and
      photosensitized formation of singlet oxygen in high quantum yields.

PMID- 25395695
TI  - Do We Really Become Smarter When Our Fluid-Intelligence Test Scores Improve?
AB  - Recent reports of training-induced gains on fluid intelligence tests have fueled
      an explosion of interest in cognitive training-now a billion-dollar industry. The
      interpretation of these results is questionable because score gains can be
      dominated by factors that play marginal roles in the scores themselves, and
      because intelligence gain is not the only possible explanation for the observed
      control-adjusted far transfer across tasks. Here we present novel evidence that
      the test score gains used to measure the efficacy of cognitive training may
      reflect strategy refinement instead of intelligence gains. A novel scanpath
      analysis of eye movement data from 35 participants solving Raven's Advanced
      Progressive Matrices on two separate sessions indicated that one-third of the
      variance of score gains could be attributed to test-taking strategy alone, as
      revealed by characteristic changes in eye-fixation patterns. When the strategic
      contaminant was partialled out, the residual score gains were no longer
      significant. These results are compatible with established theories of skill
      acquisition suggesting that procedural knowledge tacitly acquired during training
      can later be utilized at posttest. Our novel method and result both underline a
      reason to be wary of purported intelligence gains, but also provide a way forward
      for testing for them in the future.

PMID- 25395696
TI  - How Similar are Cohabiting and Married Parents? Second Conception Risks by Union
      Type in the United States and Across Europe.
AB  - The increase in births within cohabitation in the United States and across Europe
      suggests that cohabitation and marriage have become more similar with respect to
      childbearing. However, little is known about additional childbearing after first
      birth. Using harmonized union and fertility histories from surveys in 15
      countries, this study examines second conception risks leading to a live birth
      for women who have given birth within a union. Results show that women who
      continue to cohabit after birth have significantly lower second conception risks
      than married women in all countries except those in Eastern Europe, even when
      controlling for union duration, union dissolution, age at first birth, and
      education. Pooled models indicate that differences in the second conception risks
      by union type between Eastern and Western Europe are significant. Pooled models
      including an indicator for the diffusion of cohabitation show that when first
      births within cohabitation are rare, cohabiting women have significantly lower
      second conception risks than married women. As first births within cohabitation
      increase, differences in second conception risks for cohabiting and married women
      narrow. But as the percent increases further, the differentials increase again,
      suggesting that cohabitation and marriage are not becoming equivalent settings
      for additional childbearing. However, I also find that in all countries except
      Estonia, women who marry after first birth have second conception risks similar
      to couples married at first birth, indicating that the sequence of marriage and
      childbearing does not matter to fertility as much as the act of marrying itself.

PMID- 25395697
TI  - The extracts of Pacific oyster (Crassostrea gigas) alleviate ovarian functional
      disorders of female rats with exposure to bisphenol a through decreasing FSHR
      expression in ovarian tissues.
AB  - BACKGROUND: Bisphenol-A (BPA) is one of the widespread industrial compounds,
      which has adverse effects on animal and human health. The study was aimed to
      explore the effects of Crassostrea gigas extracts (CGE) in alleviating ovarian
      functional disorders of female rats with exposure to BPA and the underlying
      possible mechanism. MATERIALS AND METHODS: Eighteen four-week-old female Sprague
      Dawley (SD) rats were randomly divided into BPA group (50mg/kg BPA), BPA+CGE
      group (50mg/kg BPA+50mg/kg CGE), and control group (equivalent dosage of vehicle)
      with 6 rats in each group. After a 6-week treatment ended, the serum levels of
      estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH) were
      measured by using commercial standard assay kits. The expression levels of FSH
      receptor (FSHR) in the rat ovarian tissues were respectively detected by
      immunohistochemistry and Real-time PCR. RESULTS: CGE treatment markedly increased
      E2 levels and decreased FSH levels in the serum (P<0.05), however, the
      alterations of serum LH levels were not significant (P>0.05). The protein and
      mRNA expression levels of FSHR were the lowest in the ovaries of control rats and
      the highest in BPA rats (P<0.05). CGE treatment markedly decreased the expression
      levels of FSHR in the ovarian tissues (P<0.05). CONCLUSIONS: Crassostrea gigas
      successfully alleviates ovarian functional disorders of female rats with exposure
      to BPA partly through decreasing FSHR expression levels in the ovarian tissues.

PMID- 25395698
TI  - Effects of red palm oil and rooibos on sperm motility parameters in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Diabetes mellitus characterized by hyperglycaemia could affect sperm
      quality as a result of increased oxidative stress. This study was performed to
      investigate the effects of red palm oil (RPO), aqueous rooibos tea extracts (RTE)
      as well as their combination (RPO + RTE) on sperm motility parameters in
      streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced
      by a single administration of streptozotocin (50 mg/kg) and the rats were treated
      with red palm oil (2 ml/day) and / or aqueous rooibos tea extract (2%) for 7
      weeks. Sperm motility parameters were measured using Computer Assisted Sperm
      Analyzer (CASA). RESULTS: Hyperglycaemia negatively affected the sperm
      progressive motility significantly at p<0.05. There was a significant decrease
      (p<0.05) in sperm linearity (LIN) in the diabetic group when compared with the
      normal control group. RPO supplemented diabetic rats exhibited increased
      progressive sperm motility, sperm linearity (LIN) and wobble (WOB). Significant
      decreases (p<0.05) in straight line velocity (VSL) and average path velocity
      (VAP) of the sperms were observed in all the diabetic groups when compared to the
      control group. Significant (p<0.05) elevated levels of WOB and LIN were observed
      following RTE treatment and co-administration with RPO respectively. CONCLUSION:
      The present study suggests that red palm oil and / or rooibos administration
      exhibited no adverse effects on sperm motility parameters but rather showed some
      beneficial effects.

PMID- 25395699
TI  - Benefical therapeutic effect of Chinese Herbal Xinji'erkang formula on
      hypertension-induced renal injury in the 2-kidney-1-clip hypertensive rats.
AB  - BACKGROUND: Increase in evidence shows that the role of kidney injury in
      hypertension is important. Xinji'erkang (XJEK), a Chinese herbal formula, has
      been identified as an effective preparation in the treatment of coronary heart
      disease and myocarditis. We have previously demonstrated that XJEK attenuate
      oxidative stress and hypertension target organ damage. The aim of this study was
      to assess the renal protective function of XJEK. MATERIALS AND METHODS: Two
      Kidney One Clip (2K1C) model was adopted to induce hypertension in rats. We
      submitted male Sprague Dawley (150-180) g rats to either renal artery clipping or
      sham operation. Renal hypertension was established after four weeks of surgery.
      Rats were randomized divided into the four groups: sham-operated group (Sh-Op)
      (n=10), two-kidney, one-clip hypertension group (2K1C) (n=10), Xinji'erkang
      treatment group (XJEK) (n=10) and Fosinopril (n=10) treatment group. Drugs were
      administered orally daily for four weeks. Systolic pressures were measured every
      week using the tail-cuff apparatus. 24h before death, urine samples were
      collected for detect of urinary proteins. The kidney weight (KW) index was
      expressed as kidney weight/body weight (KW/BW). The histological changes were
      investigated by hematoxylin and eosin and Van Gieson staining.
      Immunohistochemical assay was employed to observe the intra-renal transforming
      growth factor-beta1 (TGF-beta1) protein expression. Serum creatinine (SCR) and
      blood urea nitrogen (BUN) were assayed by automatic biochemical analyzer. ELISA
      kit was used to assay Angiotensin II (Ang II) and TGF-beta1 content in serum.
      RESULTS: Administration of XJEK markedly alleviated the rise in blood pressure
      and declined LKW/BW ratio. Histo-pathological injuries including hypertrophic
      glomerular, glomerular sclerosis, glomerular and interstitial fibrosis were
      attenuated. XJEK also decreased SCR, BUN, urinary proteins in 24h urine, serum
      Ang II and TGF-beta1 concentrations and the intra-renal TGF-beta1 protein
      expression. CONCLUSION: XJEK therapy in the 2K1C hypertensive rats affects the
      rise in blood pressure and ameliorates the severity of kidney injury. The
      protective effect is most likely due to the ability of XJEK to affect the Renin
      Angiotensin-Aldosterone System (RAAS) and the TGF-beta systems.

PMID- 25395700
TI  - The antimicrobial activity of Liquidambar orientalis mill. against food pathogens
      and antioxidant capacity of leaf extracts.
AB  - BACKGROUND: Medicinal plants are an important source of substances which are
      claimed to induce antimicrobial, antimutagenic and antioxidant effects. Many
      plants have been used due to their antimicrobial treatments. Antimicrobial and
      antioxidant activities of L. orientalis have not been reported to the present
      day. The aim of this work was to investigate of the antimicrobial and antioxidant
      potentials of different extracts from L. orientalis. MATERIALS AND METHODS: The
      extracts were screened for antimicrobial activity against different food
      pathogens. These bacteria include 4 Gram positive and 3 Gram negative bacteria
      and one fungi. The leaf extracts of plant were tested by disc diffusion assay.
      The MIC was evaluated on plant extracts as antimicrobial activity. In addition
      to, the plant extracts were tested against the stable DPPH (2,2-diphenyl-1-picryl
      hydrazylhydrate) free-radical. RESULTS: The acetone, ethanol and methanol
      extracts of L. orientalis showed maximum inhibition zone of 12 mm against
      Yersinia enterocolitica, Listeria monocytogenes and Staphylococcus aureus. In
      addition to, the methanol extract displayed a strong antioxidant activity (trolox
      equivalent = 2.23 mM). CONCLUSION: L. orientalis extracts have antimicrobial, and
      antioxidant potential. Our results support the use of this plant in traditional
      medicine and suggest that some of the plant extracts possess compounds with good
      antibacterial properties that can be used as antibacterial agents in the search
      for new drugs.

PMID- 25395701
TI  - Isoflavones from Calpurnia Aurea subsp. aurea and their anticancer activity.
AB  - BACKGROUND: Calpurnia aurea is an African medicinal plant used in many countries
      in Africa to treat a range of medical conditions or disorders. Extracts of the
      plant were shown to be active in antibacterial and antioxidant assays as well as
      against lice, ticks and maggots. The aim of the study was to isolate the
      phytochemical constituents from the plant and to test them in appropriate
      bioassays dependent on the compounds isolated in order to provide a rationale for
      the use of the plant in ethno-medicine or to provide some information on its
      constituents. MATERIALS AND METHODS: The stem and bark of the plant was extracted
      with organic solvents of varying polarity and the extracts separated and purified
      using column chromatography. The isolated compounds were identified by NMR
      spectroscopy and the compounds were tested for their in vitro anticancer activity
      against breast (MCF7), renal (TK10) and melanoma (UACC62) human cell lines using
      an in house method developed at the CSIR, South Africa. RESULTS: The isoflavones,
      4',5,7-trihydroxyisoflavone (1), 7,3'-dihydroxy-5'-methoxyisoflavone (2), 7
      hydroxy-4',8-dimethoxyisoflavone (3), 7-acetoxy-4',8-dimethoxyisoflavone (4) and
      3',7-dihydroxy-4',8-dimethoxyisoflavone (5), a pterocarpan (3-acetoxy-9
      methoxypterocarpan) and a quinolizidine alkaloid (calpurnine) were isolated from
      the stem and bark of Calpurnia aurea. The tetrasubstituted isoflavone 5 was found
      to be the most active in the three cell lines amongst all the compounds tested.
      This was followed by trisubstituted isoflavone 2. CONCLUSION: The isoflavones
      showed moderate activity against the renal, melanoma and breast cancer cell lines
      tested against, with the isoflavones 2 and 5 showing the best activity of the
      compounds tested. These isoflavones may have a synergistic effect with other
      anticancer drugs.

PMID- 25395702
TI  - Antimicrobial activity of methanolic extracts of Sambucus ebulus and Urtica
      dioica against clinical isolates of methicillin resistant Staphylococcus aureus.
AB  - BACKGROUND: Increase in the emergence of drug -resistant pathogens led to the
      development of natural antimicrobials. In this study the antimicrobial effect of
      methanolic extracts of Sambucus ebulus and Urtica dioica on 16 skin and wound
      infections isolates of methicillin resistant S. aureus have been studied.
      MATERIAL AND METHODS: Solvent extraction procedure was done using soxhlet
      apparatus for extracting antimicrobial agents from freeze dried plants.
      Antibacterial activity was measured using agar well diffusion method. RESULTS:
      The MIC of Sambucus ebulus and Urtica dioica extracts against the standard strain
      of S. aureus ATCC 6538 were determined using the micro dilution method at 15 mg
      and 20 mg respectively. All the test bacteria were found sensitive to the
      Sambucus ebulus extract and only one isolate was resistant to Urtica dioica
      extract. CONCLUSION: Extracts of Sambucus ebulus and Urtica dioica possess
      antibacterial potency against MRSA isolates and may be used as a natural
      antiseptics and antimicrobial agents in medicine.

PMID- 25395703
TI  - The plights of African resources patenting through the lenses of the World Trade
      Organisation: an assessment of South Africa's rooibos tea's labyrith journey.
AB  - BACKGROUND: Just as developing states are blessed with natural resources capable
      of transforming their economies into a positive direction, the imposed World
      Trade Organisation's (WTO) mores continue to relegate them to the status of
      underdevelopment. The consequences of this on investment, trade and finance in
      Third World States (TWSs), especially Africa, are disarticulation of the economy,
      exploitation, disinvestment, unemployment, political instability and
      unavailability of relevant technology to move TWSs forward, among others. This
      gives rise to the politics behind Rooibos (Aspalathus linearis) patenting (a
      medicinal plant found only in South Africa) by various multinational corporations
      (MNCs). MATERIALS AND METHODS: This study adopted political economy approach with
      emphasis on both primary and secondary sources of data collection using content
      analysis. RESULT: There is need to adhere strictly to the issues of intellectual
      property rights (IPRs), geographical indications (GIs), prior informed consent
      (PIC), and access and sharing benefits (ASB). These have not been observed by the
      western states because of their economic of neo-imperialism to the disadvantage
      of developing states. CONCLUSION: This paper recommends that there is need for a
      regional regime such as African Regional Intellectual Property Organisation
      (ARIPO), on indigenous knowledge (IK) to patent the continental biodiversity
      resources.

PMID- 25395704
TI  - Propolis ameliorates tumor nerosis factor-alpha, nitric oxide levels, caspase-3
      and nitric oxide synthase activities in kainic acid mediated excitotoxicity in
      rat brain.
AB  - BACKGROUND: Increased nitric oxide (NO), neuronal inflammation and apoptosis have
      been proposed to be involved in excitotoxicity plays a part in many
      neurodegenerative diseases. To understand the neuro-protective effects of
      propolis, activities of Nitric oxide synthase (NOS) and caspase-3 along with NO
      and tumor necrosis factor-alpha (TNF-alpha) levels were studied in cerebral
      cortex (CC), cerebellum (CB) and brain stem (BS) in rats supplemented with
      propolis prior to excitotoxic injury with kainic acid (KA). MATERIALS AND
      METHODS: Male Sprague-Dawley rats were divided into four groups (n=6 rats per
      group) as Control, KA, Propolis and KA+Propolis. The control group and KA group
      have received vehicle and saline. Propolis group and propolis + KA group were
      orally administered with propolis (150 mg/kg body weight), five times every 12
      hours. KA group and propolis +KA group were injected subcutaneously with kainic
      acid (15 mg/kg body weight) and were sacrificed after 2 hrs. CC, CB and BS were
      separated, homogenized and used for estimation of NOS, caspase-3, NO and TNF
      alpha by commercial kits. Results were analyzed by one way ANOVA, reported as
      mean + SD (n=6 rats), and p<0.05 was considered statistically significant.
      RESULTS: The concentration of NO, TNF-alpha, NOS and caspase-3 activity were
      increased significantly (p<0.001) in all the three brain regions tested in KA
      group compared to the control. Propolis supplementation significantly (p<0.001)
      prevented the increase in NOS, NO, TNF-alpha and caspase-3 due to KA. CONCLUSION:
      Results of this study clearly demonstrated that the propolis supplementation
      attenuated the NOS, caspase-3 activities, NO, and TNF-alpha concentration and in
      KA mediated excitotoxicity. Hence propolis can be a possible potential protective
      agent against excitotoxicity and neurodegenerative disorders.

PMID- 25395705
TI  - Inhibition of three novel Radix Scutellariae extracts on immediate
      hypersensitivity.
AB  - BACKGROUND: Radix Scutellariae, a few papers reported its pharmacology activities
      including alleviate small intestines smooth muscles spasm, sedation,
      antihypertensive effect. However, the inhibition of its different organic
      extracts on immediate hypersensitivity has not bee researched. MATERIALS AND
      METHODS: To investigate the anti-immediate hypersensitivity of three extracts
      including ethanol extracts, acetone extracts, ethyl acetate extracts from Radix
      Scutellariae, four pharmacological screening model were chose, such as 4
      Aminopyridine induced pruritus model, histamine-induced mouse paw edema model,
      PCA(passive cutaneous anaphylaxis) in ear of mouse, activie cutaneous
      anaphylaxismouse (mouse ear edema test), furthermore, total IgE level in the
      sensitized mice serum was evaluated deeply. RESULTS: Ethanol group at 1.42 g/kg
      and 0.71 g/kg could greatly decrease the licking number to 1.2 and 12.7
      respectively; also keep mice paw swelling at 0.29 ml and 0.51 ml at 15 min after
      injection of histamine. Both ear passive cutaneous allergic reaction and active
      cutaneous anaphylaxis-ear swelling test demonstrated that ethanol group exhibit
      great inhibition on immediate hypersensitivity.Low IgE level was found in ethanol
      group, but high in other two groups. CONCLUSION: The ethanol extracts exhibits
      obvious strong inhibition, however, the acetone ones and ethyl acetate showed a
      little.

PMID- 25395706
TI  - Interest in and willingness to use complementary, alternative and traditional
      medicine among academic and administrative university staff in Bloemfontein,
      South Africa.
AB  - BACKGROUND: Healthcare systems worldwide are changing and the use of
      complementary, alternative and traditional medicine (CAM) form part of this
      transformation. South Africa has a large number of CAM practitioners, but they
      are not included in the official healthcare system. The aim of this study was to
      determine the perception and usage of CAM among the academic and administrative
      staff of the University of the Free State (UFS) in Bloemfontein, South Africa.
      METHODS: A questionnaire was compiled and sent electronically to all the academic
      and administrative staff of the UFS who had a university email address, to be
      completed online. RESULTS: The response rate was 5.5%, with most of the
      respondents from the Faculty of Health Sciences. The respondents (n=165) were
      mainly women of 41-60 years of age with more than one tertiary qualification.
      Most of the respondents were in good health and considered CAM as moderately
      helpful and mostly safe. Most of the CAM recommendations were not from a medical
      physician. The respondents wanted alternatives to certain medications, such as
      antibiotics. They also had good previous experience with CAM and felt that
      conventional treatment was not always effective to treat their problems. They
      identified a need for CAM in the health system. CONCLUSION: The study has
      limitations due to the data collection method and the low response rate. The
      results showed that the respondents favored a more integrated healthcare system
      including different CAM therapies, and that conventional doctors should be better
      informed about these therapies and its uses.

PMID- 25395707
TI  - Medicinal plants used as home remedies: a family survey by first year medical
      students.
AB  - BACKGROUND: There is a hierarchical organisation of knowledge in the use of
      medicinal plants in communities. Medicinal use knowledge starts in the home and
      is passed on to family members. Next in the hierarchy are neighbours, village
      elders and finally, traditional healers being the most knowledgeable. For primary
      health care this hierarchy is actively followed in seeking remedies for ailments.
      MATERIALS AND METHODS: This study was a survey of medicinal plant knowledge from
      family members of 1(st) year medical students registered at Walter Sisulu
      University. A total of 206 first year medical students participated in this study
      in 2010 and 2011. RESULTS: Results revealed 47 species used as home remedies, 32%
      of which are food plants. Leaves and roots were reported as most commonly used.
      The top five ailments managed at home were gastrointestinal problems (25 plants),
      wounds (19 plants), respiratory tract problems (19 plants), infections, including
      sexually transmitted diseases (19 plants) and pain including headaches (19
      plants). Chronic diseases such as hypertension, diabetes, cancer and reproductive
      ailments also formed a large group of diseases self-managed at home (29 plants).
      CONCLUSION: Family members hold knowledge of medicinal plant use. From this
      study, first year medical students were made aware of the relationship between
      common ailments and associated home remedies. This study forms a basis for
      further study of medicinal plants to validate their use as medicinal remedies.

PMID- 25395708
TI  - Anti-bacterial and anti-oxidant activities of leaf extracts of Combretum vendae
      (Combretecacea) and the isolation of an anti-bacterial compound.
AB  - BACKGROUND: Combretum vendae A.E. van Wyk (Combretaceae) is used for the
      treatment of bacterial related infections and oxidative related diseases by
      indigenous people of South Africa. Dried leaves extracts of C. vendae were
      investigated for bioactivity against a variety of bacterial strains and their
      antioxidant potential evaluated. MATERIALS AND METHODS: Constituents of leaf
      material were serially extracted using solvents of varying polarities, TLC
      chromatograms of the fractions were sprayed with 2,2 diphenyl-1-picrylhydrazyl
      (DPPH) to determine the presence of antioxidant compounds. Bio-autography was
      used to determine the number of antibacterial compounds active against
      Staphylococcus aureus, Enterococcus faecalis, Eschericha coli and Pseudomonas
      aeruginosa. Minimum inhibitory concentration (MIC) values were determined using
      serial microplate dilution method. The chloroform fraction was subjected to bio
      assay guided column chromatography to isolate the active compound. RESULTS: The
      mass extracted by different solvents was below 10% dry weight. MIC values for
      different extracts against different pathogens ranges from 0.08 to 0.64 mg/ml.
      The compound isolated was identified as acacetin having an Rf value of 0.28
      following elution in the Ethanol: Methanol: Water [E: M: W (10: 1.35: 1 v/v).
      Acacetin had MIC values ranging from 0.16 to 0.35 mg/ml. CONCLUSION: We report
      for the first time the isolation of acacetin as the main antibacterial compound
      from the leaves of Combretum vendae.

PMID- 25395709
TI  - Yoga effects on physical activity and sexual satisfaction among the Iranian women
      with multiple sclerosis: a randomized controlled trial.
AB  - BACKGROUND: Multiple Sclerosis (MS) is a chronic and disabling disease resulting
      in disabilities in young and middle-aged persons. In this study, researchers
      explored the effect of yoga techniques on physical activities and sexual function
      among some Iranian women with MS. MATERIALS AND METHODS: In this study, 60
      Iranian women with multiple sclerosis (MS) were placed in two equally divided
      control and case groups through random selection to assess pre-and post-effects
      of yoga exercises on their physical activities and sexual satisfaction levels.
      Women in case group were offered a series of yoga training and exercises for 3
      months, which consisted of 8 sessions per month for 60 to 90 minutes at each
      session. Yoga training program included the 3 principles of slow motions
      (Hatayoga), respiratory exercises (Pranayama) and centralization to control mind
      via meditation, expansion and stasis (Rajayoga). After 3 months both groups were
      surveyed using the initial questionnaire to evaluate and compare findings with
      the base-line data. RESULTS: Researchers found significant statistical difference
      in physical activity and sexual satisfaction levels among the women in case group
      (P=0.001). Women in case group showed improvement in physical ability while women
      in control group manifested exacerbated symptoms. CONCLUSION: Yoga techniques may
      improve physical activities and sexual satisfaction function of women with MS.

PMID- 25395710
TI  - Antioxidant activity and inhibitory effect of some commonly used medicinal plants
      against lipid per-oxidation in mice brain.
AB  - BACKGROUND: The present study compares the protective properties of aqueous
      extracts of six medicinal plants, Phyllanthus emblica, Terminalia chebula (black
      and yellow), Terminalia arjuna, Balsamodendron Mukul and Alium sativum against
      lipid per-oxidation in mice brain. METHODS: The antioxidant activities were
      analyzed by lipid per-oxidation assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      radical assay, total antioxidant activity and metal chelation. RESULTS: The
      extracts (fruits and bark) showed inhibition against thiobarbituric acid reactive
      species (TBARS) induced by pro-oxidant (10 uM FeSO4) in mice brain. Moreover, the
      free radical scavenging activities of the extracts was evaluated by the
      scavenging of DPPH radical (IC50, 23.23 +/- 1.2 ug/ml (Phyllanthus emblica),
      20.24 +/- 0.9 ug/ml (Terminalia chebula yellow) and 17.33 +/- 1.1 ug/ml
      (Terminalia chebula black), 19.44 +/- 0.45 ug/ml (Terminalia arjuna), 56.59 +/-
      2.1 ug/ml (Balsamodendron Mukul) and < 200 ug/ml (Alium sativum). CONCLUSION: The
      higher antioxidant and inhibitory effect of Terminalia chebula black in this
      study could be attributed to its significantly higher phenolic content, Fe(II)
      chelating ability, reducing ability and free radical scavenging activity.
      Therefore oxidative stress in brain could be potentially prevented by the intake
      of these plants.

PMID- 25395711
TI  - The effect of Astragalus extractive on alveolar bone rebuilding progress of tooth
      extracted socket of ovariectomied rats.
AB  - BACKGROUND: Postmenopausal osteoporosis (PMO) is an estrogen deficiency condition
      that causes severe loss of bone mass in the vertebrae and long bones. We explored
      the effect and the possible underlying mechanism of the extracts of Astragalus
      (AE) on the tooth alveolar bone rebuilding progress of postmenopausal
      osteoporosis of PMO animal models. MATERIAL AND METHODS: The PMO models were
      acquired by ovariectomy. After 8 weeks the first left maxillary molars of the
      rats were extracted and AE was administered orally for 8 weeks. Then the
      histological morphology and the transcription and expression of TGF-beta1 and TNF
      alpha in the tooth extracted socket were detected by HE dying, QRT-PCR and ELISA.
      RESULTS: The results showed that the new bone volume and TGF-beta1 was
      significantly lower in PMO group than the control group and AE group at the
      observing period. At the same time TNF-alpha in PMO group was significantly
      higher than the other two groups. Moreover AE group had no significant
      differences with the control group in all data at the observing period.
      CONCLUSION: AE has positive effect on alveolar bone rebuilding progress of tooth
      extracted socket of PMO rats. AE also has the potential to enhance the expression
      of TGF-beta1 and decrease the expression of TNF-alpha of the rebuilding tooth
      extracted socket.

PMID- 25395712
TI  - Anti-tumor effect of cactus polysaccharides on lung squamous carcinoma cells (SK
      MES-1).
AB  - BACKGROUND: Cactus polysaccharides are the active components of Opuntia dillenii
      which have been used extensively in folk medicine. In this study, we investigate
      the anti-tumor effect of cactus polysaccharides on lung squamous carcinoma cells
      SK-MES-1. MATERIALS AND METHODS: The inhibitory effect of Cactus polysaccharides
      on lung squamous carcinoma cells were detected by MTT assay. Cell cycle was
      determined by flow cytometry and cell apoptosis was determined by AnnexinV assay.
      Western-blotting was applied to detect P53 and PTEN protein expression in the
      cells treated with cactus polysaccharides. RESULTS: Results showed that different
      concentrations of wild cactus polysaccharides prevent SK-MES-1 cells growth and
      induces S phase arrest. The data also revealed that cactus polysaccharides cause
      apoptosis in SK-MES-1 cells determined by Annexin-V assay. Furthermore, cactus
      polysaccharides induced growth arrest and apoptosis may be due to the increase of
      P53 and phosphatase and tension homolog deleted on chromosome ten (PTEN) protein.
      CONCLUSION: Cactus polysaccharides have anti-tumor activity on lung squamous
      carcinoma cells.

PMID- 25395713
TI  - Inhibition effects of scorpion venom extracts (Buthus matensii Karsch) on the
      growth of human breast cancer MCF-7 cells.
AB  - BACKGROUND: To observe the inhibition effects of the Buthus matensii Karsch (BmK)
      scorpion venom extracts on the growth of human breast cancer MCF-7 cells, and to
      explore its mechanisms. METHODS: Two common tumor cells (SMMC7721, MCF-7) were
      examined for the one which wasmore sensitivity to scorpion venom by MTT method.
      Cell cycle was determined by flow cytometry. Immunocytochemistry was applied to
      detect apoptosis-related protein Caspase-3 and Bcl-2 levels, while the expression
      of cell cycle-related protein Cyclin D1 was shown by Western blotting. RESULTS:
      Our data indicated that MCF-7 was the more sensitive cell line to scorpion venom.
      The extracts of scorpion venom could inhibit the growth and proliferation of MCF
      7 cells. Furthermore, the extract of scorpion venom induced apoptosis through
      Caspase-3 up-regulation while Bcl-2 down-regulation in MCF-7 cells. In addition,
      the extracts of scorpion venom blocked the cells from G0/G1 phase to S phase and
      decreased cell cycle-related protein Cyclin D1 level after drug intervention
      compared with the negative control group. CONCLUSIONS: These results showed that
      the BmK scorpion venom extracts could inhibit the growth of MCF-7 cells by
      inducing apoptosis and blocking cell cycle in G0/G1 phase. The BmK scorpion venom
      extracts will be very valuable for the treatment of breast cancer.

PMID- 25395714
TI  - Evaluation of antioxidant and antimicrobial potential of two endangered plant
      species Atropa belladonna and Matricaria chamomilla.
AB  - BACKGROUND: Plants are the natural source of antioxidants as well as
      antimicrobial compounds that has great potentials in pharmaceutical industry. In
      the present study, two medicinal plants Atropa belladonna and Matricaria
      chamomilla were collected from Northern areas of Pakistan. MATERIALS AND METHODS:
      The extracts of the collected plants were obtained by microwave assisted
      extraction (MAE) with changing parameters, power level and time; methanol and
      ethanol were solvents used during extraction. The extracts of plants were tested
      against different bacterial strains. RESULTS: It was observed that ethanolic
      extracts of Atropa belladonna has more significant antimicrobial activity against
      S.aureus than E.coli. In parallel, methanolic extract of Matricaria chamomilla
      showed greater significant antibacterial activity against S.aureus when compared
      with E.coli. In comparison, ethanolic extracts of Matricaria chamomilla has shown
      more significant results against S. aureus than E.coli (p <= 0.05). Both plants
      had no antibacterial activity against S.typhi. The free radical scavenging
      activity observed by DPPH assay, indicate that both plants have antioxidant
      activity at all levels of concentrations in solvent tested during the present
      work. However, methanolic extracts had greater antioxidant activity when compared
      with ethanolic extracts. CONCLUSION: Present study is thus helpful in
      highlighting present potentials for antioxidant and antimicrobial properties in
      the selected plants.

PMID- 25395716
TI  - Medicinal plants cultivated in Bapedi traditional healers homegardens, Limpopo
      Province, South Africa.
AB  - BACKGROUND: Plants used for medicinal purposes are very common feature in Bapedi
      traditional healer's home-gardens, but information about their diversity and
      application is not available. MATERIALS AND METHODS: To investigate medicinal
      plants found in Bapedi healer's home-gardens, 51 traditional health practitioners
      were interviewed using a semi-structured questionnaire in 17 municipalities of
      the Limpopo Province of South Africa, during the first half of 2013. RESULTS: A
      total of 43 plant species (67.4% indigenous and 32.5% exotics) from 32 families,
      mostly from the Asteraceae and Apocynaceae (9.3% each) were documented. Species
      cultivated in home-gardens were used to treat three major groups of ailments that
      include sexually transmitted infections (44.1%), chronic diseases of life style
      (44.1%) and reproductive ailments (32.5%). The exotics Catharanthus roseus
      (54.9%) and Carica papaya (15.6%) was the most cultivated. Threatened (11.6%) and
      protected (6.9%) species are also present in home-gardens, mostly due to their
      unavailability in natural areas. CONCLUSION: This study concludes that the
      practice of cultivating medicinal plant species in home-gardens is a positive
      development that in the long term will sustain both species and accompanying
      indigenous knowledge, as well as preserve the cultural identity of the Bapedi.

PMID- 25395715
TI  - Salicylic acid alters antioxidant and phenolics metabolism in Catharanthus roseus
      grown under salinity stress.
AB  - BACKGROUND: Salicylic acid (SA) acts as a potential non-enzymatic antioxidant and
      a plant growth regulator, which plays a major role in regulating various plant
      physiological mechanisms. The effects of salicylic acid (SA; 0.05 mM) on
      physiological parameters, antioxidative capacity and phenolic metabolism, lignin,
      alkaloid accumulation in salt stressed Catharanthus roseus were investigated.
      MATERIALS AND METHODS: Catharanthus roseus seeds were grown for two months in a
      glass house at 27-30 degrees C in sunlight, and then divided into four different
      groups and transplanted with each group with the following solutions for one
      month: group I (non-saline control), group II, 100 mM NaCl, group III, 0.05 mM
      SA, group IV, 100 mM NaCl+0.05 mM SA and to determine the physiological
      parameters (DW, FW, WC), chlorophyll contents, carotenoid contents, lipid
      peroxidation, phenolics, lignin, alkaloid and enzymatic assays in each leaf pairs
      and roots. RESULTS: SA exhibited growth-promoting property, which correlated with
      the increase of dry weight, water content, photosynthetic pigments and soluble
      proteins. SA has additive effect on the significant increase in phenylalanine
      ammonia-lyase (PAL) activity, which is followed by an increase in total soluble
      phenolics and lignin contents in all leaf pairs and root of C. roseus. SA
      enhances malondialdehyde content in all leaf pairs and root. The antioxidant
      enzymes (catalase, glutathione reductase, glutathione-S-tranferase, superoxide
      dismutase, peroxidase) as well as alkaloid accumulation increased in all
      treatments over that of non-saline control but the magnitude of increase was
      found more in root. Further, the magnitude of increase of alkaloid accumulation
      was significantly higher in 100 mM NaCl, but highly significant was found in
      presence of 0.05 mM SA and intermediate in presence of both 0.05 mM SA+100 mM
      NaCl. CONCLUSION: We concluded that applied SA to salt stress, antioxidant and
      phenolic metabolism, and alkaloid accumulation were significantly altered and the
      extent of alteration varied between the SA and salt stress.

PMID- 25395717
TI  - Cognitions as mediators in the relationship between self-compassion and affect.
AB  - Previous studies suggest that self-compassion is related to numerous facets of
      mental health, but the role of cognitions in this relationship remains unknown.
      To examine the mediating role of cognitions in the relationship between self
      compassion and anxiety, depression, and life satisfaction when controlling for
      self-esteem in Japanese people, we conducted two studies. Study 1 (N = 231)
      examined the relationship between self-compassion and affect by modeling negative
      automatic thoughts as a mediator; Study 2 (N = 233) tested whether positive and
      negative automatic thoughts meditate this relationship. Results suggested that
      both self-compassion and self-esteem increased positive automatic thoughts and
      decreased trait anxiety, whereas only self-esteem increased life satisfaction and
      decreased depression directly. Positive automatic thoughts increased life
      satisfaction and decreased depression and trait anxiety, and positive automatic
      thoughts mediated the relationship between self-compassion and negative affect.
      These findings suggest that both positive and negative automatic thoughts mediate
      the relationship between self-compassion and affect in Japanese people.

PMID- 25395718
TI  - A Predictive Study of Dirichlet Process Mixture Models for Curve Fitting.
AB  - This paper examines the use of Dirichlet process (DP) mixtures for curve fitting.
      An important modelling aspect in this setting is the choice between constant or
      covariate-dependent weights. By examining the problem of curve fitting from a
      predictive perspective, we show the advantages of using covariate-dependent
      weights. These advantages are a result of the incorporation of covariate
      proximity in the latent partition. However, closer examination of the partition
      yields further complications, which arise from the vast number of total
      partitions. To overcome this, we propose to modify the probability law of the
      random partition to strictly enforce the notion of covariate proximity, while
      still maintaining certain properties of the DP. This allows the distribution of
      the partition to depend on the covariate in a simple manner and greatly reduces
      the total number of possible partitions, resulting in improved curve fitting and
      faster computations. Numerical illustrations are presented.

PMID- 25395719
TI  - Colony size, but not density, affects survival and mating success of alternative
      male reproductive tactics in a polyphenic mite, Rhizoglyphus echinopus.
AB  - Among acarid mites, a number of species are characterised by the presence of
      discontinuous morphologies (armed heteromorphs vs. unarmed homeomorphs)
      associated with alternative mating tactics (fighting vs. scramble competition).
      In Rhizoglyphus echinopus, expression of the fighter morph is suppressed, via
      pheromones, in large, dense colonies. If this mechanism is adaptive, fighters
      should have relatively lower fitness in large and/or dense colonies, due to costs
      incurred from fighting, which is often fatal. In order to test these predictions,
      we quantified the survival and mating success of fighters and scramblers in
      colonies of equal sex and morph ratios; these colonies either differed in size
      (4, 8, or 32 individuals) but not density or differed in density but not size
      (all consisted of 8 individuals). We found that the relative survival and mating
      success of fighters was inversely related to colony size, but we did not find a
      significant effect of colony density. The higher mating success of fighters in
      small colonies was due to the fact that, after killing rival males, these
      fighters were able to monopolise females. This situation was not found in larger
      colonies, in which there was a larger number of competitors and fighters suffered
      relatively higher mortality. These results indicate that morph determination,
      guided by social cues, allows for the adaptive adjustment of mating tactics to
      existing demographic conditions.

PMID- 25395720
TI  - Maintenance of familiarity and social bonding via communal latrine use in a
      solitary primate (Lepilemur leucopus).
AB  - Latrine use (i.e., the repeated use of specific defecation/urination sites) has
      been described for several mammals, including carnivores, ungulates, and
      primates. However, the functional significance of latrine use in primates has not
      been studied systematically yet. We, therefore, followed 14 radio-collared
      individuals of the pair-living white-footed sportive lemur (Lepilemur leucopus)
      for 1097 hours of continuous focal observations to investigate latrine
      distribution, seasonality of latrine use, as well as age and sex of users to test
      various hypotheses related to possible functions of latrine use, including
      territory demarcation, resource defense, signaling of reproductive state, social
      bonding, and mate defense. All individuals of a social unit exhibited communal
      use of latrines located in the core area of their territory, supporting the
      social boding hypothesis. Latrine use seems to facilitate familiarity and social
      bonding within social units via olfactory communication in this primate that
      lives in family units but exhibits low levels of spatial cohesion and direct
      social interactions. In addition, frequency of latrine visitation was higher
      during nights of perceived intruder pressure, supporting the mate defense
      hypothesis. However, animals did not react to experimentally introduced feces
      from neighboring or strange social units, indicating that urine may be the more
      important component of latrines than feces in this arboreal species. Based on a
      survey of latrine use and function in other mammals, we conclude that latrines
      facilitate communication particularly in nocturnal species with limited habitat
      visibility and in species where individuals are not permanently cohesive because
      they constitute predictable areas for information exchange.

PMID- 25395721
TI  - Queen and young larval pheromones impact nursing and reproductive physiology of
      honey bee (Apis mellifera) workers.
AB  - Several insect pheromones are multifunctional and have both releaser and primer
      effects. In honey bees (Apis mellifera), the queen mandibular pheromone (QMP) and
      e-beta-ocimene (ebeta), emitted by young worker larvae, have such dual effects.
      There is increasing evidence that these multifunctional pheromones profoundly
      shape honey bee colony dynamics by influencing cooperative brood care, a
      fundamental aspect of eusocial insect behavior. Both QMP and ebeta have been
      shown to affect worker physiology and behavior, but it has not yet been
      determined if these two key pheromones have interactive effects on hypopharyngeal
      gland (HPG) development, actively used in caring of larvae, and ovary activation,
      a component of worker reproductive physiology. Experimental results demonstrate
      that both QMP and ebeta significantly suppress ovary activation compared to
      controls but that the larval pheromone is more effective than QMP. The underlying
      reproductive anatomy (total ovarioles) of workers influenced HPG development and
      ovary activation, so that worker bees with more ovarioles were less responsive to
      suppression of ovary activation by QMP. These bees were more likely to develop
      their HPG and have activated ovaries in the presence of ebeta, providing
      additional links between nursing and reproductive physiology in support of the
      reproductive ground plan hypothesis.

PMID- 25395722
TI  - Information technologies in education of medical students at the university of
      sarajevo.
AB  - INTRODUCTION: Information and communication technology have brought about many
      changes in medical education and practice, especially in the field of
      diagnostics. During the academic year 2013/2014, at Faculty of Medicine,
      University of Sarajevo, students in the final year of the study were subjected to
      examination which aim was to determine how medical students in Bosnia and
      Herzegovina subjectively assessing their skills for using computers, have gained
      insight into the nature of Information Technology's (IT) education and possessive
      knowledge. MATERIAL AND METHODS: The survey was conducted voluntary by anonymous
      questionnaire consisting of 27 questions, divided into five categories, which are
      collecting facts about student's: sex, age, year of entry, computer skills,
      possessing the same, the use of the Internet, the method of obtaining currently
      knowledge and recommendations of students in order to improve their IT training.
      RESULTS OF THE STUDY: According to the given parameters, indicate an obvious
      difference in the level of knowledge, use and practical application of
      Information Technology's knowledge among students of the Bologna process to the
      students educated under the old system in favor of the first ones. Based on a
      comparison of similar studies conducted in Croatia, Sri Lanka, Pakistan and
      Denmark, it was observed that the level of knowledge of students of the Medical
      Faculty in Sarajevo was of equal height or greater than in these countries.

PMID- 25395723
TI  - Correlation Between the Findings of Optical Coherent Retinal Tomography (OCT),
      Stereo Biomicroscopic Images from Fundus of an Eye and Values from Visual Acuity
      of Diabetic Macular Edema.
AB  - INTRODUCTION: Diabetic maculopathy is the major cause of reduced visual acuity in
      patients with non-proliferative diabetic retinopathy and occurs on average in 29%
      of patients who have diabetes for 20 or more years. AIM: The aim of this study is
      to re examine the correlation between the findings of optical coherence retinal
      tomography, stereo bio-microscopic images from fundus of an eye and values from
      visual acuity of diabetic macular edema. In addition, the aim is to show the
      importance of various ophthalmic tests for establishing diagnosis in time.
      MATERIAL AND METHODS: The research sample consisted of 90 subjects-patients from
      Cabinet for photographic documentation, fluorescein angiography and laser
      photocoagulation in Department of Ophthalmology at the University Clinical Centre
      in Sarajevo. The study was a one-year long, prospective, clinical study. RESULTS:
      Research has shown a positive correlation between the various tests that are
      applied for the diagnosis of diabetic macular edema. Accurate and early diagnosis
      is of great importance for the treatment in time of this disease by applying
      laser photocoagulation, intravitreal injections of Anti-VEGF drugs or surgical
      treatment by Pars Plana Vitrectomy.

PMID- 25395724
TI  - Predictive Values of Optical Coherence Tomography (OCT) Parameters in Assessment
      of Glaucoma progression.
AB  - GOAL: the purpose of the current study was to estimate the predictive values of
      optical coherence tomography parameters in early, developed perimetric and
      terminal glaucoma. METHODS: 180 eyes of 120 consecutive patients were evaluated
      in this retrospective cross sectional pilot study. Copernicus Spectral -domain
      optical coherence tomography with resolution of 3 mm obtained throught the optic
      nerve head were included. All examined eyes were divided to four groups
      (healthy,early, developed perimetric glaucoma and terminal glaucoma). The values
      of the thicknes of the retinal nerve fibre layer, the size of the disk, the
      volume of the cup, the E/D parameter and the size of the RIM were compared in
      four study groups. RESULTS: The sensitivity of RNFL was 90,0%, specificity 82,0
      %, positive predictability 83,3 % and negative predictability was 89,1 %. The
      total accuracy was 86,0 % and area under curve (AUC) was 0,878 for RNFL indeks
      compering early to developed glaucoma. The sensitivity for CUP was 78%, the
      specificity was 80,8 %, the positive predictability 81,2% and the negative
      predictability was 77,5 %. The total accuracy was 79,3 % and area under curve
      (AUC) was 0,86 compering early to developed glaucoma. The sensitivity for E/D was
      82,0%, the specificity was 82,9 % the positive predictability 83,7 % and the
      negative predictability was 81,3 %. The total accuracy was 82,5 % and area under
      curve (AUC) for E/D was 0,89 compering eearly to developed glaucoma. The
      sensitivity for RIM was 78,0%, the specificity was 76,6 %, the positive
      predictability was 84,7 and the negative predictability was 67,7 %. The total
      accuracy was 77,5 % and area under curve (AUC) for the RIM compering the
      developed to terminal glaucoma was 0,792. The sensitivity of RNFL was 88,0 %, the
      specificity was 66,7 %, the positive predictability was 81,5% and the negative
      predictability was 76,9%. The total accuracy was 80,0% and the area under curve
      (AUC) for RNFL compering developed to terminal glaucoma was 0,815. The
      incrreasing 0,1 unit RNFL decreases the risk of developing glaucoma from early to
      another developed stage of glaucoma for 6,95%. The increasing of E/D for only one
      unit increases the risk to develop another stage of glaucoma for 18,75 times. The
      increasing of RNFL for only one unit decreases the risk of performing developed
      glaucoma from initial stage for 7,8%. The increasing for only one unit of CUP
      increases the risk to develop terminal glaucoma for 8,47 times and increasing for
      0,1 unit of the value of RIM decreases the risk developing terminal glaucoma for
      9,27%. The increasing for 0,01 unit of the E/D index increases the risk for
      terminal glaucoma for 23,23 times. The increasing for one unit of RNFL decreasing
      the risk developing terminal glaucoma for 5,7%.

PMID- 25395725
TI  - Analysis of the abfraction lesions formation mechanism by the finite element
      method.
AB  - INTRODUCTION: An abfraction lesion is a type of a non-carious cervical lesion
      (NCCL) that represents a sharp defect on the cervical part of tooth, caused by
      occlusal biomechanical forces. The largest prevalence of the NCCL is found on the
      mandibular first premolar. The goal of the study is, by means of a numerical
      method - the finite element method (FEM), in an appropriate computer program,
      conduct a stress analysis of the mandibular premolar under various static loads,
      with a special reference to the biomechanics of cervical tooth region. MATERIAL
      AND METHODS: A three-dimensional model of the mandibular premolar is gained from
      a uCT x-ray image. By using the FEM, straining of the enamel, dentin, peridontal
      ligament and alveolar bone under axial and paraxial forces of 200 [N] is
      analyzed. The following software were used in the analysis: CT images processing
      CTAn program and FEM analysis-AnsysWorkbench 14.0. RESULTS: According to results
      obtained through the FEM method, the calculated stress is higher with eccentric
      forces within all tested tooth tissue. The occlusal load leads to a significant
      stress in the cervical tooth area, especially in the sub-superficial layer of the
      enamel (over 50 MPa). The measured stress in the peridontal ligament is
      approximately three times higher under paraxial load with regard to the axial
      load, while stress calculated in the alveolar bone under paraxial load is almost
      ten times higher with regard to the axial load. The highest stress values were
      calculated in the cervical part of the alveoli, where bone resorption is most
      commonly seen. CONCLUSION: Action of occlusal forces, especially paraxial ones,
      leads to significant stress in the cervical part of tooth. The stress values in
      the cervical sub-superficial enamel layer are almost 5 times higher in relation
      to the superficial enamel, which additionally confirms complexity of
      biomechanical processes in the creation of abfraction lesions.

PMID- 25395726
TI  - A HTK-based Method for Detecting Vocal Fold Pathology.
AB  - INTRODUCTION: In recent years a number of methods based on acoustic analysis were
      developed for vocal fold pathology detection. These methods can be categorized in
      two categories:a) detection based on the phonemes b) detection based on the
      continuous speeches. While there are many researches which belong to the first
      category, there are few efforts for detecting vocal fold pathology based on the
      continuous speeches (second category). METHODS: In this work, a method based on
      the Hidden Markov model Toolkit (HTK) for detecting vocal fold pathology in the
      Russian digits is developed which belongs to the second category. It employs a
      three state HMM for modeling each phoneme. RESULTS: According to the results of
      the experiments, the proposed method achieves the 90% of detection accuracy.
      CONCLUSION: The proposed method is one of the first works for detecting vocal
      fold pathology based on the Russian digits (from 1 to 10) for Belorussian people.
      The reported accuracy is rather good and therefore it is recommended to use it as
      an auxiliary tool in medical centers.

PMID- 25395727
TI  - Genomics Analysis of Replicative Helicase DnaB Sequences in Proteobacteria.
AB  - Replicative Helicase DnaB interacts with DnaA, DnaC, DnaG, and DNA polymerase III
      to commence replication, increase the movement rate of the replication fork, and
      to assemble part of the primosome. The formation of the replication fork is
      limited by the ability to load DnaB to the DNA, thus DnaB has shown to be vital
      to a large extent. In the absence of DnaB, the replication fork is not maintained
      and in a state of inactivity the replication fork degrades and collapses. To
      further understand importance of this enzyme from an evolutionary perspective, a
      genomic analysis DnaB protein sequences, chosen from five Proteobacteria
      subclasses was performed. Our analysis indicates that, DnaB replicative helicases
      of Alphaproteobacteria and Epsilonproteobacteria have diverged at an earlier
      stage from Betaproteobacteria, Deltaproteobacteria and Gammaproteobacteria as
      well as from one another. Our results were further supported, when we reanalyzed
      and reconstructed the phylogenetic tree after the inclusion of sequences from
      Actinobacteria and Firmicute phylum. In addition, Betaproteobacteria,
      Deltaproteobacteria, and Gammaproteobacteria appear to share a closer common
      ancestor than from the other two subclasses. The Dot-plot analysis indicated
      that, the region between amino acid residues 320 to 400 was strongly conserved
      among all five subclasses. 

PMID- 25395728
TI  - Evaluation of the scientific outputs of researchers with similar h index: a
      critical approach.
AB  - BACKGROUND AND PURPOSE: h-index has been always reviewed as one of the most
      useful criteria for evaluating the scientific outputs of researchers by the
      sciencometric experts. In this study, the h-index of 40 Iranian researchers
      accompanied with its relationship to assessment criteria of scientific outputs
      such as the number of articles, scientific age, number of citations and self
      citation were reviewed. MATERIALS AND METHODS: The first part of this study was
      related to the literature review. But the information of 40 Iranian researchers'
      Citation Reports was observational extracted from WOS database and the Pearson
      correlation coefficient test was used to answer the research hypotheses. RESULTS:
      Citation analysis showed that 40 selected researchers published 877 articles in
      web of science up to 9 January 2013. These articles have been cited 3858 time.
      The average of their h-index was estimated 38.5 +/-12.12 Correlation coefficient
      test showed that there was a significant and direct relationship between the h
      index and the number of papers, the number of citations and self-citation
      (Sig>0.05) but there was no significant relationship between scientific age and h
      index (Sig> 0.05). CONCLUSIONS: Analysis of the data showed that the quantitative
      and qualitative indicators of the researchers with the same h-index had
      considerable differences. Therefore, only the h-index should not be a criterion
      for scientific ranking of the researchers and other complementary indexes such as
      M parameter and G index along with h-index must be used to be able to more
      accurately determine the degree of scientific influence of the researchers with
      the same h.

PMID- 25395729
TI  - Bibliometric analysis of stem cell publications in iran.
AB  - OBJECTIVE: The purpose of this study is to examine qualitative and quantitative
      states of stem cell research in Iran in order to extract information production
      patterns. METHODS: The data were extracted by searching through the Science
      Citation Index (SCI) Expanded database related to January 2013. The number of
      published articles and frequency of their citation were used as indices of the
      quality and quantity of information production. RESULTS: Total number of Iranian
      stem cell articles and proceedings indexed in Web of Science until 2012 was 709.
      The highest frequency belonged to the multiple institution category (45-50% of
      the articles during 2005-2012). The highest CPP rate (29.7) belonged to the
      international articles written by the authors from other countries with Iranian
      coauthors. CONCLUSION: Although cooperation between more authors from different
      institutions and countries can increase the quality of scientific articles,
      results of this research showed that international research must be distinguished
      in terms of author sequence.

PMID- 25395730
TI  - Intelligent data analysis: the best approach for chronic heart failure (CHF)
      follow up management.
AB  - OBJECTIVE: Intelligent data analysis has ability to prepare and present complex
      relations between symptoms and diseases, medical and treatment consequences and
      definitely has significant role in improving follow-up management of chronic
      heart failure (CHF) patients, increasing speed and accuracy in diagnosis and
      treatments; reducing costs, designing and implementation of clinical guidelines.
      THE AIM: The aim of this article is to describe intelligent data analysis methods
      in order to improve patient monitoring in follow and treatment of chronic heart
      failure patients as the best approach for CHF follow up management. METHODS:
      Minimum data set (MDS) requirements for monitoring and follow up of CHF patient
      designed in checklist with six main parts. All CHF patients that discharged in
      2013 from Tehran heart center have been selected. The MDS for monitoring CHF
      patient status were collected during 5 months in three different times of follow
      up. Gathered data was imported in RAPIDMINER 5 software. RESULTS: Modeling was
      based on decision trees methods such as C4.5, CHAID, ID3 and k-Nearest Neighbors
      algorithm (K-NN) with k=1. Final analysis was based on voting method. Decision
      trees and K-NN evaluate according to Cross-Validation. CONCLUSION: Creating and
      using standard terminologies and databases consistent with these terminologies
      help to meet the challenges related to data collection from various places and
      data application in intelligent data analysis. It should be noted that
      intelligent analysis of health data and intelligent system can never replace
      cardiologists. It can only act as a helpful tool for the cardiologist's decisions
      making.

PMID- 25395731
TI  - The status of hospital information systems in Iranian hospitals.
AB  - BACKGROUND: The area of e-Health is broad and has an excellent growth potential.
      An increasing number of experts believe that e-Health will fuel the next
      breakthroughs in health system improvements throughout the world, but there is
      frequent evidence of unsustainable use of e-Health systems in medical centres,
      particularly hospitals, for different reasons in different countries. Iran is
      also a developing country which is presently adopting this promising technology
      for its traditional healthcare delivery but there is not much information about
      the use of e-Health systems in its hospitals, and the weakness and opportunities
      of utilization of such Hospital Information Systems (HIS). METHODS: For this
      research, a number of Hospitals from Isfahan, Iran, are selected using convenient
      sampling. E-health research professionals went there to observe their HIS and
      collect required data as a qualitative survey. The design of interview questions
      was based on the researchers' experiences and knowledge in this area along with
      elementary interviews with experts on HIS utilization in hospitals. RESULTS:
      Efficient administration of e-health implementation improves the quality of
      healthcare, reduces costs and medical errors, makes healthcare resources
      available to rural areas, etc. However, there are numerous issues affecting the
      successful utilization of e-health in Hospitals, such as a lack of a perfect HIS
      implementation plan and well-defined strategy, inadequate IT-security for the
      protection of e-health-related data, improper training and educational issues,
      legal challenges, privacy concerns, improper documentation of lessons learned,
      resistance to the application of new technologies, and finally a lack of recovery
      plan and disaster management. These results along with some informative stories
      are extracted from interview sessions to uncover associated challenges of HIS
      utilization in Iranian hospitals. CONCLUSION: The utilization of e-health in
      Iranian hospitals, particularly those in Isfahan, is subject to several
      challenges and there is no proper long-term strategy plans for HIS initiation,
      development, and improvement in Iranian hospitals. In order to address these
      problems, six recommendations are provided. Hence, human resource and e-health
      professionals from third party consultancy companies along with medical
      university scholars have to assist such hospitals to undertake the proposed
      solutions in order to provide proper plans to overcome future challenges and have
      a mature HIS in accordance with expected HIS utilization from hospitals and
      medical universities.

PMID- 25395732
TI  - Telemedicine in gastroenterohepatology.
AB  - Telemedicine itself is not the medical profession, it is not a medical specialty,
      but the way in which the medical profession conduct its activity. Therefore we
      are talking about tele otorhinolaryngology, tele cardiology or tele pathology. In
      the definition of a multitude of telemedicine that can be found in the literature
      is the following: Telemedicine is a system that supports the process of health
      care by providing ways and means for more efficient exchange of information that
      allows multitude of activities related to health care, including health care and
      health personnel, including education, administration and treatment. Telemedicine
      applications include tele diagnosis, tele consultation, tele monitoring, tele
      care, tele consultations and remote access to information contained in one or
      more databases. It turned out that telemedicine is an important factor in
      technological, professional, financial and organizational uniformity of
      development of the health system. Telemedicine, although a new area, to a large
      extent already changed the ways of providing health care, and even more influence
      on the ways of designing the future of medicine. 

PMID- 25395733
TI  - Critical thinking: the development of an essential skill for nursing students.
AB  - Critical thinking is defined as the mental process of actively and skillfully
      perception, analysis, synthesis and evaluation of collected information through
      observation, experience and communication that leads to a decision for action. In
      nursing education there is frequent reference to critical thinking and to the
      significance that it has in daily clinical nursing practice. Nursing clinical
      instructors know that students face difficulties in making decisions related to
      clinical practice. The main critical thinking skills in which nursing students
      should be exercised during their studies are critical analysis, introductory and
      concluding justification, valid conclusion, distinguish of facts and opinions,
      evaluation the credibility of information sources, clarification of concepts and
      recognition of conditions. Specific behaviors are essentials for enhancing
      critical thinking. Nursing students in order to learn and apply critical thinking
      should develop independence of thought, fairness, perspicacity in personal and
      social level, humility, spiritual courage, integrity, perseverance, self
      confidence, interest for research and curiosity. Critical thinking is an
      essential process for the safe, efficient and skillful nursing practice. The
      nursing education programs should adopt attitudes that promote critical thinking
      and mobilize the skills of critical reasoning. 

PMID- 25395734
TI  - The most influential scientists in the development of medical informatics (1):
      francois gremy.

PMID- 25395735
TI  - Reduction of CO2 using a Rhenium Bipyridine Complex Containing Ancillary BODIPY
      Moieties.
AB  - The reduction of carbon dioxide to chemical fuels such as carbon monoxide is an
      important challenge in the field of renewable energy conversion. Given the
      thermodynamic stability of carbon dioxide, it is difficult to efficiently
      activate this substrate in a selective fashion and the development of new
      electrocatalysts for CO2 reduction is of prime importance. To this end, we have
      prepared and studied a new fac-ReI(CO)3 complex supported by a bipyridine ligand
      containing ancillary BODIPY moieties ([Re(BB2)(CO)3Cl]). Voltammetry experiments
      revealed that this system displays a rich redox chemistry under N2, as
      [Re(BB2)(CO)3Cl] can be reduced by up to four electrons at modest potentials.
      These redox events have been characterized as the ReI/0 couple, and three ligand
      based reductions - two of which are localized on the BODIPY units. The ability of
      the BB2 ligand to serve as a non-innocent redox reservoir is manifest in an
      enhanced electrocatalysis with CO2 as compared to an unsubstituted Re-bipyridine
      complex lacking BODIPY units ([Re(bpy)(CO)3Cl]). The second order rate constant
      for reduction of CO2 by [Re(BB2)(CO)3Cl] was measured to be k = 3400 M-1s-1 at an
      applied potential of -2.0 V versus SCE, which is roughly three times greater than
      the corresponding unsubstituted Re-bipyridine homologue. Photophysical and
      photochemical studies were also carried out to determine if [Re(BB2)(CO)3Cl] was
      a competent platform for CO2 reduction using visible light. These experiments
      showed that this complex supports unusual excited state dynamics that precludes
      efficient CO2 reduction and are distinct from those that are typically observed
      for fac-ReI(CO)3 complexes.

PMID- 25395736
TI  - Corrosion current density prediction in reinforced concrete by imperialist
      competitive algorithm.
AB  - This study attempted to predict corrosion current density in concrete using
      artificial neural networks (ANN) combined with imperialist competitive algorithm
      (ICA) used to optimize weights of ANN. For that reason, temperature, AC
      resistivity over the steel bar, AC resistivity remote from the steel bar, and the
      DC resistivity over the steel bar are considered as input parameters and
      corrosion current density as output parameter. The ICA-ANN model has been
      compared with the genetic algorithm to evaluate its accuracy in three phases of
      training, testing, and prediction. The results showed that the ICA-ANN model
      enjoys more ability, flexibility, and accuracy.

PMID- 25395737
TI  - Higher order processes in random Raman lasing.
AB  - Random Raman lasers offer a unique opportunity to study many exciting dynamics of
      light propagation in turbid media. One of the most notable features observed to
      exist in the recently discovered random Raman laser are the presence of higher
      order stimulated Raman scattering (SRS) processes. The higher order Stokes
      generation likely comes from photons that have the longest pathlengths, thus have
      the most gain. This makes these photons particularly likely to offer interesting
      insight into wave propagation effects such as coherent backscattering and optical
      Anderson localization. In this work, we use Monte Carlo simulations to
      investigate how these higher order processes occur and what properties they are
      expected to exhibit when considering only transport equation dynamics. This
      knowledge will allow us to look for deviations from this theory in future
      experiments to determine if wavelike properties play an active role in random
      Raman lasing.

PMID- 25395738
TI  - Model-Based, Closed-Loop Control of PZT Creep for Cavity Ring-Down Spectroscopy.
AB  - Cavity ring-down spectrometers typically employ a PZT stack to modulate the
      cavity transmission spectrum. While PZTs ease instrument complexity and aid
      measurement sensitivity, PZT hysteresis hinders the implementation of cavity
      length-stabilized, data-acquisition routines. Once the cavity length is
      stabilized, the cavity's free spectral range imparts extreme linearity and
      precision to the measured spectrum's wavelength axis. Methods such as frequency
      stabilized cavity ring-down spectroscopy have successfully mitigated PZT
      hysteresis, but their complexity limits commercial applications. Described herein
      is a single-laser, model-based, closed-loop method for cavity length control.

PMID- 25395739
TI  - From the Editor's desk.

PMID- 25395741
TI  - Gonadotropin-releasing hormone analogs: Understanding advantages and limitations.
AB  - Pituitary stimulation with pulsatile gonadotropin-releasing hormone (GnRH)
      analogs induces both follicle-stimulating hormone (FSH) and luteinizing hormone
      (LH). Pituitary gonadotropin secretions are blocked upon desensitization when a
      continuous GnRH stimulus is provided by means of an agonist or when the pituitary
      receptors are occupied with a competitive antagonist. GnRH antagonists were not
      available originally; therefore, prolonged daily injections of agonist with its
      desensitizing effect were used. Today, single- and multiple-dose injectable
      antagonists are also available to block the LH surge and thus to cause
      desensitization. This review provides an overview of the use of GnRH analogs
      which is potent therapeutic agents that are considerably useful in a variety of
      clinical indications from the past to the future with some limitations. These
      indications include management of endometriosis, uterine leiomyomas, hirsutism,
      dysfunctional uterine bleeding, premenstrual syndrome, assisted reproduction, and
      some hormone-dependent tumours, other than ovulation induction. 

PMID- 25395740
TI  - Evidence-based management of recurrent miscarriages.
AB  - Recurrent miscarriages are postimplantation failures in natural conception; they
      are also termed as habitual abortions or recurrent pregnancy losses. Recurrent
      pregnancy loss is disheartening to the couple and to the treating clinician.
      There has been a wide range of research from aetiology to management of recurrent
      pregnancy loss. It is one of the most debated topic among clinicians and
      academics. The ideal management is unanswered. This review is aimed to produce an
      evidence-based guidance on clinical management of recurrent miscarriage. The
      review is structured to be clinically relevant. We have searched electronic
      databases (PubMed and Embase) using different key words. We have combined the
      searches and arranged them with the hierarchy of evidences. We have critically
      appraised the evidence to produce a concise answer for clinical practice. We have
      graded the evidence from level I to V on which these recommendations are based. 

PMID- 25395742
TI  - Impact of dehydroepiandrosterone on clinical outcome in poor responders: A pilot
      study in women undergoing in vitro fertilization, using bologna criteria.
AB  - OBJECTIVE: To evaluate the role of dehydroepiandrosterone (DHEA) supplementation
      in women with poor ovarian response (POR) undergoing in vitro fertilization
      (IVF). DESIGN: Prospective case-control study. SETTING: Private tertiary
      fertility clinic. MATERIALS AND METHODS: 31 infertile women with POR diagnosed as
      per the Bologna criteria. INTERVENTIONS: DHEA supplementation for 2 months and a
      subsequent IVF cycle, after two previous IVF cycles with POR. MAIN OUTCOME
      MEASURES: Dose and duration of gonadotropin therapy, oocyte yield, embryo number
      and quality, pregnancy and live birth rate. RESULTS: No difference was seen in
      gonadotropin requirement before and after DHEA supplementation. There was a
      significant increase in total and metaphase II oocytes (5.9 +/- 0.68 vs. 2.73 +/-
      0.24; 4.45 +/- 0.47 vs. 2.09 +/- 0.26), fertilization (3.65 +/- 0.49 vs. 2.00 +/-
      0.27), Grade I embryos (1.52 +/- 0.25 vs. 0.55 +/- 0.18), pregnancy rate (30% vs.
      9.1%) and live birth rate (25% vs 0%) in those who completed the cycle, following
      DHEA supplementation. CONCLUSIONS: Dehydroepiandrosterone supplementation results
      in an improvement in oocyte yield, embryo quality, and live birth rate in a group
      of women with POR having undergone at least two previous failures due to POR.

PMID- 25395743
TI  - New laparoscopic peritoneal pull-through vaginoplasty technique.
AB  - BACKGROUND: Many reconstructive surgical procedures have been described for
      vaginal agenesis. Almost all of them are surgically challenging, multi-staged,
      time consuming or leave permanent scars on abdomen or skin retrieval sites. AIM:
      A new simple technique using laparoscopic peritoneal pull-through in creation of
      neo vagina has been described. MATERIAL AND METHODS: Total of thirty six patients
      with congenital absence of vagina (MRKH syndrome) were treated with laparoscopic
      peritoneal pull through technique of Dr. Mhatre between 2003 till 2012. The
      author has described 3 different techniques of peritoneal vaginoplasty. RESULTS:
      This technique has given excellent results over a period of one to seven years of
      follow-up. The peritoneal lining changes to stratified squamous epithelium
      resembling normal vagina and having acidic Ph. CONCLUSION: Apart from giving
      excellent normal vaginal function, as the ovary became accessible per vaginum
      three patients underwent ovum retrieval and pregnancy using surrogate mother,
      thus making this a fertility enhancing procedure.

PMID- 25395744
TI  - Follicular steroid hormones as markers of oocyte quality and oocyte development
      potential.
AB  - CONTEXT: Various components of follicular fluid are suggested as biochemical
      predictors of oocyte quality. Previous studies of follicular steroid hormone
      levels have shown disparate results when related with fertilization outcomes.
      AIM: The objective of the study was to relate the levels of steroid hormones of
      each individual follicle with oocyte maturation, fertilization results, embryo
      quality, and pregnancy rates. SETTINGS AND DESIGN: Prospective cohort study in a
      university hospital. METHODS: In 31 patients, who underwent intracytoplasmic
      sperm injection, it was performed an ultrasound guided aspiration of follicular
      fluid of the first two mature follicles from each ovary. Follicular levels of
      estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate were
      measured by chemiluminescent immunoassay. STATISTICAL ANALYSIS: Generalized
      estimating equation model. RESULTS: In follicular fluids with mature oocyte
      presence, in normal as well as in failed fertilization, there was a positive
      correlation between follicular testosterone and progesterone (r = 0.794, P =
      0.0001 and r = 0.829, P = 0.0001). Progesterone levels were higher in cases of
      normal fertilization compared to failed fertilization (P = 0.003). B quality
      embryos came from oocytes immersed in follicular fluids with higher estradiol
      values and higher estradiol/progesterone and estradiol/testosterone ratios than
      those of C quality (P = 0.01; P = 0.0009; P = 0.001). Estradiol levels were
      higher in patients who achieved pregnancy (P = 0.02). CONCLUSION: The analysis of
      follicular hormone composition could be considered as an additional tool in
      oocyte selection.

PMID- 25395745
TI  - A comparative study between cleavage stage embryo transfer at day 3 and
      blastocyst stage transfer at day 5 in in-vitro fertilization/intra-cytoplasmic
      sperm injection on clinical pregnancy rates.
AB  - OBJECTIVE: To evaluate the efficacy of blastocyst transfer in comparison with
      cleavage stage transfer. STUDY DESIGN: A randomized, prospective study was
      conducted in Infertility clinic, Department of Obstetrics and Gynecology, Mahatma
      Gandhi Hospital, Jaipur on 300 patients aged 25-40 years undergoing in-vitro
      fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) cycle from May 2010
      April 2011. When three or more Grade-I embryos were observed on day 2 of culture,
      patients were divided randomly into two study groups, cleavage stage transfer and
      blastocyst transfer group having 150 patients each. Primary outcomes evaluated
      were, Clinical pregnancy rate and Implantation rate. The results were analyzed
      using proportions, standard deviation and Chi-square test. RESULTS: Both the
      groups were similar for age, indication and number of embryos transferred.
      Clinical pregnancies after blastocyst transfer were significantly higher 66
      (44.0%) compared to cleavage stage embryo transfer 44 (29.33%) (P < 0.01).
      Implantation rate for blastocyst transfer group was also significantly higher (P
      < 0.001). CONCLUSION: Blastocyst transfer having higher implantation rate and
      clinical pregnancy rate lead to reduction in multiple pregnancies.

PMID- 25395746
TI  - Periodicity in the levels of serum plasminogen activator inhibitor-1 is a robust
      prognostic factor for embryo implantation and clinical pregnancy in ongoing IVF
      cycles.
AB  - CONTEXT: Plasminogen activator inhibitor-1 (PAI-1) has been inversely correlated
      to proteolytic extracellular-matrix degradation exerted by urokinase-type (u-PA)
      and tissue-type plasminogen activators (t-PA). Any pathological disturbance in
      PAI-1 levels may lead to several pregnancy complications. AIMS: To assess the
      influence of periodicity in serum PAI-1 levels on embryo implantation and
      clinical pregnancy outcome in IVF cycles. SETTINGS AND DESIGN: Prospective study
      of 120 IVF cycles at private infertility centre. MATERIAL AND METHODS:
      Endometrial response (ER) assessment by measuring Endometrial thickness (cm) and
      echopattern (grade). Serum PAI-1(ng/ml) measurement by ELISA method on day of
      hCG, day of ET and days 7 and 14 of ET. Main outcome measure was clinical
      pregnancy. STATISTICAL ANALYSIS: Student "t" test, ANOVA, Post-test for linear
      trend, Pearson Correlation. RESULTS: PAI-1 levels declined from dhCG to dET
      (318.8 +/- 36.1 to 176.1 +/- 28.4) whereas they increased steadily from dET to d7
      to d14ET (176.1 +/- 28.4 to 285.2 +/- 30.4 to 353.5 +/- 150.4; P = 0.0004) in
      pregnant group (n = 31). Conversely, dhCG to dET levels increased in both
      nonpregnant (n = 75; 173.8 +/- 18.3 to 280.8 +/- 26.1) and biochemical pregnancy
      BCP (n = 14; 172.7 +/- 31.1 to 216 +/- 30.1) groups. The rising pattern from dET
      to d7 to d14ET was not observed in non-pregnant and BCP groups. ER thickness and
      grade shared significant correlation with serum PAI-1 on dET (Pearson r: ER =
      0.28, Grade = 0.29) and d7ET (Pearson r: ER = 0.40, Grade = 0.23). CONCLUSIONS:
      Periodicity in serum PAI-1 levels offers a robust prognostic factor for
      predicting clinical pregnancy outcome. The dhCG to dET PAI-1 transition is a
      decisive factor for either transferring embryos in same/ongoing cycle or
      cryopreserving them and postponing ET to subsequent natural cycle.

PMID- 25395747
TI  - Differential protein expression in seminal plasma from fertile and infertile
      males.
AB  - AIM: The aim of this study was to analyze human seminal plasma proteins in
      association with male fertility status using the proteomic mass spectrometry
      technology Surface-Enhanced Laser Desorption Ionization Time-of-Flight (SELDI-TOF
      MS). MATERIALS AND METHODS: Semen analysis was performed using conventional
      methods. Protein profiles of the seminal plasma were obtained by SELDI-TOF mass
      spectrometry over a strong anion exchanger, ProteinChip((r)) Q10 array. RESULTS
      AND CONCLUSION: We found statistically significant differences in motility and
      sperm count between fertile and infertile men. In addition, we observed ten
      seminal proteins that are significantly up-regulated in the infertile group. In
      conclusion, comparison of seminal plasma proteome in fertile and infertile men
      provides new aspects in the physiology of male fertility and might help in
      identifying novel markers of male infertility.

PMID- 25395748
TI  - Quantitative evaluation of p53 as a new indicator of DNA damage in human
      spermatozoa.
AB  - BACKGROUND: Sperm DNA integrity is considered an important parameter to assess
      seminal fluid quality and can be used as a predictive test of potential
      fertility. Amongst the various tests to determine sperm DNA integrity, one is the
      Acridine Orange test. Recent studies have demonstrated the importance of p53 in
      maintaining sperm DNA integrity. The aim of this study was to assess if a p53
      ELISA assay could be a new indicator of DNA damage in human spermatozoa.
      MATERIALS AND METHODS: 103 human semen samples were evaluated using both Acridine
      Orange test and p53 ELISA and results were compared. RESULTS: A clear correlation
      between the values measured by two methods was obtained. CONCLUSIONS: If this
      hypothesis will be confirmed by further studies, the p53 ELISA assay could become
      a new and more precise indicator of DNA damage in human spermatozoa.

PMID- 25395749
TI  - Spontaneous successful pregnancy in posthypophysectomy hypopituitarism: A rare
      case report.
AB  - Pregnancy in patients with pan-hypopituitarism following surgery of pituitary
      adenoma is rare and considered high risk. Hormonal dysfunction in these patients
      involves more than one axis (gonadotrophic, thyroidal, and adrenal). However,
      advance in infertility treatment have led to the increased pregnancy rate in
      hypopituitarism women. We present a case of nonfunctioning pituitary
      macroadenoma, who after pituitary surgery (hypophysectomy) developed
      hypopituitarism followed by multiple tuberculoma brain with hydrocephalus with
      arachnoiditis. She conceived spontaneously after 9 years of pituitary surgery and
      carried her pregnancy to the term. Elective caesarean section was done at 38
      weeks and both infant and mother are well. The case highlights the rarity of the
      phenomenon and the safe outcome of the pregnancy with proper replacement. 

PMID- 25395750
TI  - Laparoscopic gonedectomy in a case of complete androgen insensitivity syndrome.
AB  - Complete Androgen insensitivity syndrome is a disorder of hormone resistance
      characterized by a female phenotype in an individual with an XY karyotype. The
      pathogenesis of CAIS involves a defective androgen receptor gene located on X
      chromosome at Xq11-12and end organ insensitivity to androgens, although androgen
      concentrations are appropriate for the age of the patient. There are three major
      types of androgen insensitivity syndrome: Complete androgen insensitivity
      syndrome, minimal androgen insensitivity syndrome, and partial androgen
      insensitivity syndrome. Management of androgen insensitivity syndrome includes
      multidisciplinary approach and involves gonedectomy to avoid gonadal tumors in
      later life. Hormone replacement therapy (HRT) and psychological support are
      required in long-term basis. 

PMID- 25395751
TI  - Embryo cryopreservation in a case of acute promyelocytic leukemia, incidentally
      diagnosed during ovarian stimulation for in-vitro fertilization.
AB  - A 31-year-old woman presented with secondary infertility, a history of previous
      miscarriage and two ectopic pregnancies. Salpingectomy had been performed for the
      left ruptured tubal pregnancy whereas the right unruptured tubal pregnancy was
      managed medically. In-vitro fertilization (IVF) was advised to treat tubal factor
      infertility of 2 years duration. The patient developed fever and cough on day-10
      of ovarian stimulation. Complete blood count and peripheral smear with marked
      leukocytosis were suggestive of acute leukemia. After obtaining the patient's
      informed consent, 18 oocytes were retrieved. Following intra cytoplasmic sperm
      injection, 14 eggs were fertilized, and the resulting embryos were cryopreserved.
      On a referral to a hemato-oncologist, a bone marrow biopsy was performed, which
      confirmed acute promyelocytic leukemia (APL). Literature review suggests this to
      be the first case of APL reported during the course of ovulation stimulation for
      IVF. 

PMID- 25395753
TI  - A billion smiles welcome the world of dentistry.

PMID- 25395752
TI  - Antibiotics supplemented culture media.

PMID- 25395754
TI  - Antioxidant mix: A novel pulpotomy medicament: A scanning electron microscopy
      evaluation.
AB  - AIM: This study aims to evaluate the clinical, radiographic, and histological
      success rate of antioxidant mix as a new pulpotomy agent for primary teeth.
      SETTINGS AND DESIGN: Commercially available antioxidants, namely Antioxidants
      plus trace elements (OXIn-Xt(tm), India) were used. MATERIALS AND METHODS: This
      prospective study was carried out on 36 primary molar teeth in 32 children, with
      age that ranged from 6 to 9 years. Regular conventional pulpotomy procedure
      followed by placement of antioxidant mix over the radicular orifice was done.
      Recall was scheduled for 3, 6, and 9 months, respectively, after treatment.
      RESULTS: Thirty-six pulpotomized primary molars were available for follow-up
      evaluations. Scanning electron microscopy analysis of samples showing convex
      shaped hard tissue barrier formation may be proof of the role of antioxidant
      material in localization and direction and morphology of the hard tissue barrier.
      One tooth which presented with pain was assessed as unsuccessful. CONCLUSION:
      Quite promising clinical, radiographic, and histological results of antioxidants
      in the present study shows their potential to be an ideal pulpotomy agent.

PMID- 25395755
TI  - Evaluation of calcium ion release and change in pH on combining calcium hydroxide
      with different vehicles.
AB  - INTRODUCTION: Intracanal medicaments have traditionally been used in endodontics
      to disinfect root canals between appointments. Calcium hydroxide is widely used
      as an intracanal medicament for disinfection and to promote periapical healing.
      It is stable for long periods, harmless to the body, and bactericidal in a
      limited area. The efficacy of calcium hydroxide as a disinfectant is dependent on
      the availability of the hydroxyl ions in the solution that depends on the vehicle
      in which the calcium hydroxide is carried. In general, three types of vehicles
      are used: Aqueous, viscous or oily. Some in vitro studies have shown that the
      type of vehicle has a direct relationship with the concentration and the velocity
      of ionic liberation as well as with the antibacterial action when the paste is
      carried into a contaminated area. AIM OF THE STUDY: To evaluate the calcium ion
      release and measure the change in pH of the environment that occurred when
      calcium hydroxide was combined with different vehicles (distilled water,
      propylene glycol, calcium hydroxide containing gutta-percha points and chitosan)
      over different time periods. MATERIALS AND METHODS: Forty single rooted
      mandibular first premolar teeth were decoronated for this study. Working length
      was established and the root canals were enlarged and irrigation accomplished
      with 2 ml of NaOCl solution after every file. The teeth were then randomly
      divided into four groups. The canals were then packed with different preparations
      of calcium hydroxide using the following vehicles-distilled water, propylene
      glycol, gutta-percha points and chitosan. Calcium ion release in different groups
      was analyzed using an ultraviolet spectrophotometer at 220 nm. The change in pH
      of was determined using a pH meter. Results were statistically evaluated using
      one-way ANOVA test. RESULT: For calcium ion release, Group 2 showed cumulative
      drug release of 81.97% at the end of 15 days, whereas Group 1, 3 and 4 showed a
      release of 99.53, 17.98, 74.93% respectively with a significant difference among
      all groups. Group 1 reached the highest Ca(2+) level (39.79%) at the end of 1 day
      but showed almost complete release of calcium hydroxide at the end of 15 days.
      Group 3 showed least calcium ion release (17.98%) at 15 days. Group 4 showed a
      sustained release of Ca(+2) ions from 74% at 15 days to 95% at the end of 30
      days. After the 1(st) h; Group 1 showed the highest pH level (11.8). However, pH
      reduced to 7.8 at the end of 30 days in this group. Group 2 showed the highest pH
      value (10.35), followed by Group 4 (10.32) after 30 days. CONCLUSION: Chitosan
      can be used as a promising vehicle for calcium hydroxide to maintain an alkaline
      pH and to allow sustained release of calcium ions in the root canal system.

PMID- 25395756
TI  - Salivary alkaline phosphatase and calcium in caries-active type II diabetes
      mellitus patients: An in vivo study.
AB  - BACKGROUND: Diabetes Mellitus is a metabolic syndrome, affecting the oral health
      in various ways with dental caries being one of the most common problems
      encountered. Saliva is one of the most abundant secretions in the human body with
      a variety of natural protective and defence molecules bathing the oral cavity
      maintaining equilibrium. Its collection is easy and non-invasive. AIMS: To
      compare and evaluate salivary alkaline phosphatase levels and calcium ion levels
      between caries active type II diabetes mellitus patients and non-diabetics.
      MATERIALS AND METHODS: This study was carried out on caries-active age and gender
      matched 60 non-diabetic and 60 patients with known Type II diabetes mellitus
      subjects of age group 25-50 years with DMFT index >10. Saliva sample was
      collected to analyse for alkaline phosphatase enzyme and concentration of calcium
      ions using Agappe kits. STATISTICAL ANALYSIS: Student 't' test was used to
      correlate the salivary electrolyte concentration in non- diabetic and diabetic
      patients with dental caries. A 'P' value of 0.05 or less was considered
      significant. Results are presented as mean +/- standard deviation (X +/- SD).
      RESULTS: The alkaline phosphatase (ALP) activity in saliva was higher in diabetic
      patients when compared to that of non-diabetic patients with salivary calcium
      ions were significantly higher in non-diabetic individuals. CONCLUSION: Diabetes
      Mellitus patients are more prone to dental caries, hence require intervention to
      improve the quality of saliva.

PMID- 25395757
TI  - Clinical and radiographic evaluation of intra-bony defects in localized
      aggressive periodontitis patients with platelet rich plasma/hydroxyapatite graft:
      A comparative controlled clinical trial.
AB  - BACKGROUND: Aggressive periodontitis is a characterized by rapid attachment loss,
      bone destruction and familial aggregation. Platelet-rich plasma (PRP) has been
      proposed to promote regeneration of the lost periodontal tissues. The aim of this
      study was to evaluate and compare the efficacy of PRP combined with
      hydroxyapatite (HA) graft in the treatment of intra-bony defects in localized
      aggressive periodontitis (L-AgP) patients. MATERIALS AND METHODS: Ten L-AgP
      patients having bilateral intra-bony defect >=2 mm and probing depth (PD) >=6 mm
      were randomly treated either with the PRP/HA graft or HA graft alone. The
      clinical (plaque control record, bleeding on probing index, PD, and relative
      attachment level [RAL]), and radiographic parameters (size of the bone defect)
      were recorded pre- and post-operatively at 3, 6, and 12 months. RESULTS: After 12
      months, for both maxillary and mandibular arches, the mean PD decrease was
      significantly more (P < 0.05) for the test group than the control group (3.2 mm
      vs. 1.9 mm and 3.6 mm vs. 1.9 mm, respectively). Furthermore, the mean RAL
      decrease in both maxillary and mandibular arches was significantly more (P <
      0.05) for the test group than the control group (3.0 mm vs. 1.2 mm and 3.1 mm vs.
      1.4 mm, respectively). Radiographically, the test group showed significantly more
      defect fill as compared with the control group. CONCLUSION: Both treatments
      provided significant improvements in clinical and radiographic parameters in a 12
      month postoperative period. PRP/HA group presented superior results regarding PD
      reduction, clinical attachment gain and radiographic bone fill than HA group.

PMID- 25395758
TI  - A study of mandibular fractures over a 5-year period of time: A retrospective
      study.
AB  - OBJECTIVE: This study aims to evaluate and compare with the existing literature
      on the etiology, pattern, gender, and anatomical distribution of mandibular
      fractures. MATERIALS AND METHODS: The data of 225 cases were analyzed over a
      period of 5 years between March 2009 and November 2013. Of this 110 were
      unilateral, 23 bilateral, 18 symphysis and 74 multiple fractures. RESULTS: Males
      are more affected than females. The peak incidence rate is occurring in 30-35
      years of age group. The most common fracture site is parasymphysis and least
      common site is ramus of mandible. The most common etiological factor is road
      traffic accident (RTA) (45.3%) followed by falls (42.6%), assaults (8.9%), sport
      injuries (2.2%), and gunshot wounds (0.89%). CONCLUSION: Thus, we conclude that
      RTA is the leading cause of mandibular fractures and males are more affected. The
      most common site is parasymphysis fracture in association with angle fracture. We
      observed that gender was significantly associated with body and angle fracture (P
      = 0.04) and significant relationship between etiology with multiple site fracture
      such as (parasymphysis-angle), (body-condyle), (body-angle), and (symphysis
      condyle) was observed (P <= 0.05).

PMID- 25395759
TI  - Morphometric analysis of cervical vertebrae morphology and correlation of
      cervical vertebrae morphometry, cervical spine inclination and cranial base angle
      to craniofacial morphology and stature in an adult skeletal class I and class II
      population.
AB  - OBJECTIVE: The study was carried out to compare the morphometry of the cervical
      column between adult Class I and Class II individuals and between gender and to
      analyze the correlation between the cervical column morphology, the cranial base
      angle, the craniocervical inclination with craniofacial morphology and stature of
      Angles Class I and Class II individuals. MATERIALS AND METHODS: The data for this
      institutional retrospective study were systematically selected according to the
      specified inclusion and exclusion criteria from the pretreatment cephalometric
      radiographs of 19 male and 30 female patients visiting the Department of
      Orthodontics, Manipal College of Dental Sciences, Mangalore, Manipal University,
      based on their ANB angle. The radiographs were traced and digitized. The
      reliability of the variables describing the cranial base and vertical and
      sagittal craniofacial dimensions was assessed. CONCLUSIONS: Our results showed
      that there was no statistically significant variation in the cervical vertebrae
      dimensions between Class I and Class II patients. There was found to be a
      definite sexual dimorphism, which was not statistically significant. Correlation
      exists between sagittal skeletal patterns, especially mandibular length and
      cervicovertebral morphology, but its use to classify the subjects in different
      sagittal classes is questionable.

PMID- 25395760
TI  - Evaluation of the value of bone training (progressive bone loading) by using the
      Periotest: A clinical study.
AB  - AIM: The aim of this clinical study was to determine if progressive bone loading
      was effective in improving bone density and rigidity of implants. MATERIALS AND
      METHODS: 11 implants were placed with conventional loading and 14 implants were
      placed with progressive loading. The Periotest instrument was used to assess
      implant mobility. Mean difference of values were recorded in both qualities of
      bone. RESULTS: Conventional loading in poor quality bone showed a significant
      decrease in rigidity of the bone as compared to conventional loading in good
      quality of bone. Progressive loading in both poor and good quality bone showed a
      significant increase in bone rigidity. CONCLUSION: Implants should not be loaded
      conventionally in poor quality bone but should be progressively loaded to prevent
      decrease in density and rigidity around implants.

PMID- 25395761
TI  - Comparative antiplaque and antigingivitis effectiveness of tea tree oil mouthwash
      and a cetylpyridinium chloride mouthwash: A randomized controlled crossover
      study.
AB  - OBJECTIVE: The aim of this study was to compare the antiplaque and antigingivitis
      effects of a mouthwash containing tea tree oil (TTO) with a cetylpyridinium
      chloride (CPC) mouthwash. MATERIALS AND METHODS: This was a randomized 4 * 4,
      controlled, cross-over, involving 20 healthy volunteers in a 5-day plaque re
      growth model. Test mouthwashes were TTO (Tebodont((r))) and a mouthwash
      containing CPC 0.05% (Aquafresh((r))). A 0.12% chlorhexidine (CHX) mouthwash (Oro
      Clense((r))) was used as positive and colored water (placebo [PLB]) as negative
      controls. Gingival bleeding index (GBI) and plaque index (PI) scores were
      recorded before and after each test period. Test periods were separated with 2
      weeks washout period. RESULTS: All four mouthwashes significantly (P < 0.001)
      reduced the GBI scores when compared to the baseline GBI scores. There was no
      significant difference between PLB and active mouthwashes in the GBI scores. CHX
      and CPC mouthwashes were found more effective in reducing the PI scores than TTO
      and PLB mouthwashes. There was no significant difference in PI scores of CHX and
      CPC mouthwashes. CONCLUSION: 0.05% CPC mouthwash can be an alternative to CHX
      mouthwash since it is alcohol free and found as efficient as CHX in dental plaque
      reduction with lesser side effects. More studies are needed to test
      antigingivitis effects of the mouthwashes used in this study, preferably without
      initial scaling and polishing.

PMID- 25395762
TI  - Evaluation of mixed dentition analyses in north Indian population: A comparative
      study.
AB  - INTRODUCTION: Mixed dentition regression equations analyses (Moyers, Tanaka
      Johnston) are based on European population, reliability of these methods is
      questionable over other population. MATERIALS AND METHODS: The present study was
      conducted on total 260 study models. This study was done in two phases. In the
      first phase, linear regression equations were made. In the second phase,
      comparison of actual values of sum of mesiodistal width of canine, first and
      second premolars with the predicted values proposed by Moyers, Tanaka-Johnston,
      and the new proposed mixed dentition analysis for North Indian population were
      made. RESULTS: Set of four linear regression equations for predicting sum of
      mesiodistal width of permanent canine, first premolar and second premolar in
      North Indian population from sum of mesiodistal width of mandibular incisors and
      mandibular first molars, were proposed as; (a) for males, maxillary arch, Y = 2.9
      + 0.40X, (b) mandibular arch Y = 3.91 + 0.37X (c) for females, maxillary arch Y =
      0.56 + 0.45X (d) mandibular arch Y = 1.14 + 0.42X. Moyers and Tanaka-Johnston,
      mixed dentition analysis, is found to be overestimating the mesiodistal width of
      unerupted canine and premolars in North Indian population.

PMID- 25395763
TI  - Evaluating the effectiveness of oral health education program among mothers with
      6-18 months children in prevention of early childhood caries.
AB  - BACKGROUND: Mothers play a key role as transmitters of oral health behavior for
      their children. Hence increasing their knowledge about positive attitude toward
      desirable oral health behaviors regarding their children will lead to the better
      oral health of the children. AIM: The aim was to evaluate the effectiveness of
      oral health education program among mothers with 6-18 months old children in the
      prevention of early childhood caries. MATERIALS AND METHODS: A total of 480
      mothers with 6-18 months old children were selected using cluster randomization
      of the primary health center. The allocated mothers were assigned into three
      groups: Motivation group (group A), traditional health education group (group B)
      and control group (group C). Clinical examination was carried out to record the
      dental decay of the child. STATISTICAL ANALYSIS: The data was analyzed using SPSS
      13. Evaluation of statistical significance between groups was made using the Chi
      square test, ANOVA and Kruskal-Wallis. RESULTS: Mean number of decayed teeth was
      0.23 + 0.58 in group A that was significantly less as compared to 0.39 + 0.79 and
      1.17 + 1.32 in group B and C, respectively. CONCLUSION: Motivational intervention
      was more effective in reducing dental decay in the children as compared to the
      other two groups.

PMID- 25395764
TI  - Comparative evaluation of serum C-reactive protein levels in chronic and
      aggressive periodontitis patients and association with periodontal disease
      severity.
AB  - OBJECTIVE: C-reactive protein (CRP) is an acute-phase reactant and has been
      proved to be a significant predictor of future cardiovascular events. Recent
      studies have demonstrated a correlation between periodontitis and elevated CRP
      levels. However, most of the studies have focused on chronic periodontitis and
      very few studies are done in patients with aggressive periodontitis. The aim of
      this study was to determine and compare the relative levels of serum CRP in
      aggressive and chronic periodontitis patients. MATERIALS AND METHODS: A total of
      75 systemically healthy subjects were divided into three groups: Group I,
      nonperiodontitis subjects; group II, chronic generalized periodontitis patients
      and group III, generalized aggressive periodontitis patients. All participants
      were subjected to quantitative CRP analysis using enzyme-linked immunosorbent
      assay. RESULTS: Mean CRP levels were significantly greater in both group II and
      III as compared to group I and group III having greater level than group II.
      Furthermore, CRP levels positively correlated with the amount of periodontal
      destruction as measured by probing depth and clinical attachment loss.
      CONCLUSION: The present study indicates a positive correlation between CRP and
      periodontal disease severity with particular concern in younger individuals that
      could be a possible underlying pathway in the association between periodontal
      disease and the observed higher risk for cardiovascular disease in periodontitis
      patients.

PMID- 25395765
TI  - Effect of rapid maxillary expansion on sleep characteristics in children.
AB  - INTRODUCTION: Rapid maxillary expansion (RME) is an orthopedic treatment
      procedure routinely used to treat constricted maxillary arches and also a
      potential additional treatment in children presenting with sleep-disordered
      breathing (SDB). AIMS AND OBJECTIVES: The main objective of this study was to
      evaluate the effects of RME on sleep characteristics in children. MATERIALS AND
      METHODS: Polysomnography was done on children of 8-13 years of age before
      expansion (T0), after expansion (T1) and after a period of 3 months after
      retention (T2). Bonded rapid maxillary expander was cemented in all children.
      Inter-molar distance was also measured at T0 and T2. STATISTICAL ANALYSIS:
      Nonparametric Friedman test was used for comparing the averages of sleep
      parameters at different time period (T0, T1, T2). Wilcoxon signed ranks test was
      used for comparing the averages of inter-molar width (T0-T2). P < 0.05 were
      considered as significant. RESULTS: All children showed an improvement in sleep
      parameters with an increase in sleep efficiency, decreased in arousal and
      desaturation index after expansion. Total sleep time showed a statistically
      significant increase after expansion. A statistically significant increase in
      inter-molar distance was obtained after expansion. CONCLUSIONS: Rapid maxillary
      expansion is a useful treatment option for improving quality of sleep even in
      normal children without SDB. It also induces widening of the maxilla, corrects
      posterior crossbites and improves maxillary and mandibular dental arch
      coordination.

PMID- 25395766
TI  - Cytological analysis of the periodontal pocket in patients with aggressive
      periodontitis and chronic periodontitis.
AB  - BACKGROUND: Oral exfoliative cytology includes the study and interpretation of
      the features cells exfoliated from the oral mucosa. The aim of this study was to
      analyze cytological changes in the periodontal pocket of patients with different
      clinical stages of aggressive periodontitis (AP) and chronic periodontitis (CP).
      MATERIALS AND METHODS: Patients aged 24-54 years, of whom 41 were diagnosed with
      AP, 40 with CP, sub-classified as mild, moderate and severe periodontitis, and 40
      healthy individuals who were the control group. Samples of the epithelium of the
      periodontal pocket were taken for the cytological study. RESULTS: Superficial and
      intermediate cell values were significantly greater in patients with AP than in
      patients with CP or the control group. Histiocyte number was higher in patients
      with CP than in those with AP, and differed significantly in both types of
      periodontitis compared to the control group. There were significant differences
      in polymorphonuclear neutrophil leukocytes when both types of periodontitis were
      compared to the control group. Microbial flora was statistically higher in
      patients with CP, and there were differences between patients with periodontitis
      and the control group. CONCLUSIONS: The cytological study demonstrated that
      patients with AP had greater tissue damage, shown by the increase in intermediate
      and superficial cells of the epithelium of the periodontal pocket compared to the
      group of healthy subjects and to a lesser extent, to patients with CP. Only
      superficial cells made it possible to differentiate the sub-stages of the
      disease.

PMID- 25395767
TI  - Scattering properties of a composite resin: Influence on color perception.
AB  - BACKGROUND: The properties of the composite materials and the clinical expertise
      while layering them carry many esthetic implications in restorative dentistry.
      AIMS: The aim of the present study is to assess the influence of scattering
      properties of G-aenial A2 shade on color perception when used in esthetic
      restorations. MATERIALS AND METHODS: TWO COMPOSITE RESINS WERE EVALUATED IN THIS
      STUDY: Gradia Direct (shade A3) and G-aenial (shade A2). A colorimetric
      evaluation according to the CIE L*a*b* system, relative to standard illuminant A
      against a white background, was performed to assess the referred chameleonic
      properties of G-aenial when used in simulated clinical situations. STATISTICAL
      ANALYSIS USED: The differences in color change between the test group G-aenial
      and the test Group Gradia Direct were considered clinically not perceptible
      (DeltaE* <3.3). Differently, the differences in color change were considered
      clinically perceptible (DeltaE* >3.3) between the control group G-aenial and the
      control group Gradia Direct and between the test group G-aenial and the control
      specimens obtained with G-aenial. The CIE Lab parameters which brought to DeltaE
      were investigated using t-test (P < 0.05). RESULTS AND CONCLUSIONS: Color
      harmonization in simulated clinical conditions depends on different factors
      related to dentine and to composite resins. In this study dentine variables were
      dropped in order to analyze the influence of thickness and of the composition of
      the composite resin.

PMID- 25395768
TI  - Awareness of emergency management of dental trauma.
AB  - AIM: Traumatic dental injuries frequently occur in society and may occur at home.
      The ultimate prognosis of an avulsed tooth occurring in a child may depend on the
      parents' knowledge of appropriate emergency measures. This study is aimed at
      evaluating the awareness level of a sample of Indian (Rohtak, Haryana) parents in
      the management of dental trauma. MATERIALS AND METHODS: A total of 1500 parents
      were surveyed using a self-administered structured questionnaire. The
      questionnaire was divided into three parts. The tabulated data were statistically
      analyzed using the Chi-square test. RESULT: This study indicated a low level of
      knowledge regarding tooth avulsion and replantation procedures to be followed in
      emergency. The residing area and age of parent did not affect the knowledge and
      awareness of parents. Moreover, well-educated parents also had very little or no
      information about dental trauma first-aid. The lack of significance in correct
      answers between those with and without such experience indicated that past
      experience did not seem to have increase the knowledge of the correct emergency
      procedures. Very little or no information about tooth avulsion and replantation
      had been given to most of them. CONCLUSION: Dental injury prevention and
      management should be recognized as a major public health issue and adequate
      resources to be allocated for research in this area. Educational programs to
      improve the knowledge and awareness among the parents have to be implemented.

PMID- 25395769
TI  - Validation of a novel behavior prediction scale: A two-center trial.
AB  - CONTEXT: Prediction of the child's behavior can adequately equip the dentist in
      rendering effective and efficient dental treatment. AIM: This study was planned
      to evaluate and validate a specially prepared questionnaire as a child behavior
      prediction scale. DESIGN: A two-center cross-sectional study was done to validate
      the new scale. MATERIALS AND METHODS: Children aged 3-12 years (n = 296), from
      two different centers participated in this study. The questionnaire used was a 10
      point observational scale. Observations involved perceiving overt and subtle
      behavioral characteristics of a child, to assess the child's behavior in the
      dental office before treatment. An independent observer approached the children
      and their parents in the waiting room. The child's behavior was then evaluated by
      the dentist using Frankl behavior rating scale during and after treatment. The
      prediction of behavior compared to the Frankl scale was assessed and validated.
      STATISTICAL ANALYSIS: Sensitivity, specificity tests, and receiver operating
      curve analysis were used to validate the new scale and calculate the cut-off
      score for positive and negative behavior. All data were processed by SPSS
      software (16.0, SPSS Inc., Chicago, Ill, USA). RESULTS: The best cut-off score to
      predict a positive Frankl rating was >= 8.0 in both the centers. The sensitivity
      and specificity scores were 93.4% and 62.5% in center 1; 83.1% and 59.6% in
      center 2 respectively. CONCLUSION: This novel prediction scale can be of great
      importance in predicting children's behavior in the dental environment.

PMID- 25395770
TI  - Why WITS? Why not a way beyond?
AB  - INTRODUCTION: WITS appraisal is a common parameter in cephalometrics to assess
      maxillo-mandibular skeletal relationship as an adjunct to angle ANB. The high
      variability of the WITS appraisal is attributable to difficulties or inaccuracies
      in identifying the occlusal plane or variations due to tooth eruption, dental
      development or treatment changes by vertical movement of incisors, molars, or
      both. AIM: An extracranial reference line common to both denture bases, instead
      of the occlusal plane is proposed to assess antero-posterior jaw relationships.
      MATERIALS AND METHODS: A true vertical obtained by plumb line was recorded, while
      taking the cephalogram for 40 subjects. A line drawn perpendicular to this true
      vertical gave a stable and reproducible extracranial true horizontal (HOR)
      reference line. The linear distance between perpendiculars from points A and B
      was measured as an adjunct to angle ANB. RESULT: The Pearson's product moment
      correlation coefficient calculated for the entire sample indicated higher
      correlation coefficient (r = 0.8712) for the linear measurements on HOR (AH-BH)
      with respect to the angle ANB when compared with the WITS readings (AO-BO) (r =
      0.549). CONCLUSION: The horizontal appraisal method proposed eliminates the
      demerits of the occlusal plane and has the merits of simplicity and accuracy in
      comparison to WITS appraisal.

PMID- 25395771
TI  - An unusual presentation of pyogenic granuloma of the lower lip.
AB  - Exophytic growth of the oral cavity often presents a diagnostic challenge because
      a diverse group of the pathologic process can produce such lesions. Inflammatory
      hyperplasia is one of the important etiology behind the exophytic growths of the
      oral cavity. The pyogenic granuloma (PG) is the most common type of inflammatory
      hyperplasia found in the oral cavity especially in the gingiva. Extragingival
      occurrence of PG is very rare. This case report has described an extragingival PG
      which occurred on the lower labial mucosa in a 54-year-old male patient. 

PMID- 25395772
TI  - Alginate base to evade lingual trimming of the mandibular cast.

PMID- 25395773
TI  - Integration of the Herbst and Begg appliance in the management of severe Class II
      malocclusion.
AB  - The efficacy of the Herbst appliance in a normalizing sagittal relationship in
      patients with a Class II malocclusion is well-documented. This case report
      describes the treatment of a 14-year-old male patient with severe Class II
      Division 1 malocclusion due to retrognathic mandible and mildly prognathic
      maxilla, convex profile, and lip trap. He had severely proclined maxillary
      incisors and retroclined mandibular incisors, overjet of 13 mm and overbite of 7
      mm. Since the patient was in the peak pubertal growth phase, growth modulation
      was carried out with the Herbst appliance for 8 months, followed by fixed
      appliance therapy with the Begg appliance for 11 months. Combination of Herbst
      and Begg appliance led to a very favorable treatment outcome and greatly improved
      the patient's appearance. 

PMID- 25395774
TI  - Mandibulofacial dysostosis (Treacher Collins syndrome): A case report and review
      of literature.
AB  - Treacher Collins syndrome (TCS) or Franceschetti syndrome is an autosomal
      dominant disorder of craniofacial development with variable phenotypic
      expression. It presents with characteristic facial appearance enabling it to be
      easily recognizable. A case of a 10-year-old girl having TCS is briefly described
      in this article. A review of the etiology, clinical features, differential
      diagnosis, and treatment options are also discussed. 

PMID- 25395775
TI  - Massive granular cell ameloblastoma with dural extension and atypical morphology.
AB  - Ameloblastomas are rare histologically benign, locally aggressive tumors arising
      from the oral ectoderm that occasionally reach a gigantic size. Giant
      ameloblastomas are a rarity these days with the advent of panoramic radiography
      in routine dental practice. Furthermore, the granular cell variant is an uncommon
      histological subtype of ameloblastoma where the central stellate reticulum like
      cells in tumor follicles is replaced by granular cells. Although granular cell
      ameloblastoma (GCA) is considered to be a destructive tumor with a high
      recurrence rate, the significance of granular cells in predicting its biologic
      behavior is debatable. However, we present a rare case of giant GCA of remarkable
      histomorphology showing extensive craniofacial involvement and dural extension
      that rendered a good prognosis following treatment. 

PMID- 25395776
TI  - Interdisciplinary approach for the management of bilaterally impacted maxillary
      canines.
AB  - Interdisciplinary approach for the management of malocclusion provides a holistic
      approach of patient management. Prudent treatment planning is necessary to
      achieve the various treatment goals. This case report describes the orthodontic
      management of a 16-year-old adolescent female patient with bilateral labially
      impacted maxillary canines. The problems associated with impacted maxillary
      canines and the biomechanical interventions used for this patient are discussed.
      The treatment protocol involved surgical intervention, followed by sequential
      traction of the impacted teeth. An interdisciplinary approach to treatment with
      different mechanical strategies led to the achievement of the desired esthetic,
      functional, and occlusal treatment goals. 

PMID- 25395777
TI  - Managing the severely proclined maxillary anteriors by extracting traumatized
      right maxillary central incisor.
AB  - A 14-year-old girl reported with severely proclined maxillary anterior teeth with
      fractured and discolored right maxillary central incisor with questionable
      prognosis. Autotransplantation of premolar to replace central incisor was
      considered a risky option as patient was 14-year-old with presence of advanced
      root development of premolar. The immediate placement of the prosthetic implant
      was also not possible because of patient's age. Therefore, it was decided to use
      the space obtained by extracting questionable maxillary right central incisor for
      orthodontic purpose and also sacrificing the healthy premolar is invariably an
      excessive biological cost for a modest functional and aesthetic gain. Hence, the
      treatment plan for this case includes extraction of right maxillary central
      incisor and left maxillary first premolar, movement of right maxillary lateral
      incisor mesially, achieving normal axial inclination of maxillary anteriors with
      normal overjet and overbite. Mandibular arch was treated nonextraction due to
      congenitally missing central incisors with presence of normally inclined lower
      anteriors thereby maintaining Angles class I occlusion. Tipping, usually, seen in
      Begg mechanotherapy was used for our advantage to correct severely proclined
      maxillary anteriors with simultaneous bite opening mechanics. Case was completed
      in 19 months and posttreatment records including photographs, radiographs and
      study models were made. Begg wrap around the retainer was placed in the maxillary
      arch allowing natural settling of occlusion. 

PMID- 25395778
TI  - Platelet rich fibrin and xenograft in treatment of intrabony defect.
AB  - For complete periodontal regeneration, delivery of growth factors in the local
      environment holds a great deal in adjunct to bone grafts. Platelet rich fibrin
      (PRF) is considered as second generation platelet concentrate, consisting of
      viable platelets, releasing various growth factors such as platelet-derived
      growth factor, vascular endothelial growth factor, transforming growth factor,
      insulin-like growth factor, epidermal growth factor and basic fibroblast growth
      factor. Hence, this case report aims to investigate the clinical and radiological
      (bone fill) effectiveness of autologous PRF along with the use of xenogenic bone
      mineral in the treatment of intra bony defects. Intrabony defect was treated with
      autologous PRF along with the use of xenogenic bone mineral. A decrease in
      probing pocket depth, gain in clinical attachment level and significant bone fill
      was observed at end of 6 months. The result obtained with the use of PRF may be
      attributed to the sustained and simultaneous release of various growth factors
      over a period of 7 days. In this case report, the positive clinical impact of
      additional application of PRF with xenogenic graft material in the treatment of
      periodontal intrabony defect was seen. 

PMID- 25395779
TI  - A newer simultaneous space creation, eruption, and adjacent root control spring
      for the management of impacted tooth.
AB  - USUALLY, TREATMENT OF IMPACTION INCLUDES: Welcome preparation (to create space),
      surgical exposure and attachment to the impacted tooth and the orthodontic
      guidance for the eruption of the impacted tooth. Sometimes, due to deficiency of
      space, creation of space for impacted tooth requires first, and space regaining
      efforts may require the distal movement of posterior teeth and or mesial movement
      of anterior teeth in the arch, but it may create some problems. To overcome the
      unwanted problem in this clinical situation and to reduce overall treatment
      duration of the patient, we have developed the Simultaneous space creation,
      Eruption and Adjacent root control spring to control crown as well as root
      movement.

PMID- 25395780
TI  - Ectomesenchymal chondromyxoid tumor: A rare case report.
AB  - Ectomesenchymal chondromyxoid tumor (ECMT) is a rare benign neoplasm of uncertain
      histogenesis, which exclusively involves the oral cavity, particularly the
      tongue. Clinically, it presents as slow growing, painless, firm, submucosal
      swelling exclusively occurring on the anterior dorsum of the tongue.
      Histopathologically, it comprised well circumscribed, unencapsulated lobular
      proliferation of fusiform and polygonal cells, with varying degree of
      cellularity, with neoplastic cells often seen in a myxoid, chondroid or
      hyalinized background. Until date, only 40 cases have been reported in the
      literature. Most documented lesions involve anterior tongue, however 2 cases in
      posterior tongue and one palatal tumor has been described. Here, we present a
      rare case diagnosed clinically and histopathologically as (ECMT) in a 7-year-old
      girl with the size of the lesion 5.0 cm making this case even rarer and throwing
      some light on this distinct entity. 

PMID- 25395781
TI  - Solitary intraosseous neurofibroma: Report of a unique case.
AB  - Neural tumors located centrally in jaw bones are relatively rare compared with
      soft tissue neurofibromas. Less than 50 cases have been reported in the
      literature with a predilection for mandible. This article aims to elucidate a
      unique case of intraosseous neurofibroma of mandible in a 62-year-old edentulous
      female patient associated with facial asymmetry due to the swelling extending
      from the right body of mandible to left body of mandible. The uniqueness of this
      case is related to the age and extensiveness of this lesion. A review of
      clinical, radiographic, histological, and immunohistochemical features, and the
      surgical management pertaining to this case are discussed along with a review of
      the literature. 

PMID- 25395782
TI  - Sclerosing mucoepidermoid carcinoma of minor salivary gland.
AB  - Sclerosing mucoepidermoid carcinoma (SMEC) is extremely rare variant of the
      mucoepidermoid carcinoma, which is the most common primary malignancy of the
      salivary glands. As its name suggests, SMEC is characterized by an intense
      central sclerosis that occupies the entirety of an otherwise typical tumor,
      frequently with an inflammatory infiltrate of plasma cells, eosinophils, and/or
      lymphocytes at its peripheral regions, but its uncompanionship with inflammatory
      cell infiltration might explain its progressive stage of the sclerosis. The
      sclerosis associated with these tumors may obscure their typical morphologic
      features and result in diagnostic difficulties. Tumor infarction and
      extravasation of mucin eventuating in reactive fibrosis are two mechanisms of
      formation that have been suggested as underlying this morphologic variant.
      Morphologic evidence in support of the mucin extravasation hypothesis was
      identified, as small pools of mucin were present throughout the tumor. 

PMID- 25395783
TI  - Hereditary gingival fibromatosis and its management: 2-year follow-up.
AB  - Hereditary gingival fibromatosis (HGF) is a rare hereditary condition
      characterised by slow, progressive, nonhemorrhagic, fibrous enlargement of
      gingiva caused by increase in sub-mucosal connective tissue component. This paper
      presents a case report of a 14-year-old male suffering from HGF with positive
      family history. After through clinical examination, routine blood investigation
      was advised. All the parameters were within normal physiological limits. Surgical
      excision of enlarged gingival mass was planned after meticulous scaling and root
      planning. Patient was recalled 1-week after surgery. Postoperative healing was
      good and desired crown lengthening was achieved with significant improvement in
      speech and masticatory problems. There was no recurrence of the disease even
      after 2 years follow-up. 

PMID- 25395784
TI  - Knowledge and Attitude of Parents/Caretakers toward Management of Avulsed Tooth
      in Maharashtrian Population: A Questionnaire Method.
AB  - BACKGROUND: Traumatic injuries to teeth and their supporting structures during
      childhood are one of the major problems faced by the dentist in day to day
      practice. Children usually encounter minor accidents in their routine activities
      and hence, it of utmost importance to provide emergency care to reduce such
      outcomes. Most of children with dental trauma present late for treatment due to
      lack of awareness and knowledge among parents/caretakers resulting in unfavorable
      long-term prognosis. This study was conducted to evaluate by means of a
      questionnaire, the knowledge, and usual attitude of the parents/caretakers about
      the management of avulsed tooth in children of age group 5-14 years. MATERIALS
      AND METHODS: The questionnaire containing 6 questions was distributed among 200
      parents/caretakers who participated in the study. The questions assessed the
      knowledge and attitude of parents toward avulsed tooth and its management.
      Statistical analysis was performed using Statistical Package for Social Sciences
      version 17.0. RESULTS: A lack of technical information regarding the preservation
      and management of avulsed tooth was observed among the parents/caretakers. The
      education status of the study population when associated with the knowledge
      variables of avulsion showed that most of the variables had statistically
      significant association with P < 0.04. CONCLUSION: These data reinforce the need
      to provide the population with some important information regarding the emergency
      management of avulsed tooth. This warrants the need of effective communication
      between dental professionals and caretakers for better handling of dental
      emergencies.

PMID- 25395785
TI  - Comparative Evaluation of Shear Bond Strength of Recycled Brackets using
      Different Methods: An In vitro Study.
AB  - BACKGROUND: Debonding of brackets commonly occurs during orthodontic treatment.
      Due to increase in costs replacement of a damaged bracket is not liked by the
      dentist. This study is done to assess the shear bond strength of recycled
      brackets using different methods. MATERIALS AND METHODS: This study was conducted
      using five groups of orthodontic brackets (0.022" * 0.028", MBT prescription)
      bonded on the premolars mounted in cubes. Other materials required were cubical
      trays, bonding material, light cure unit, universal testing machine, digital
      camera and sandblasting unit. RESULTS: From the result of ANOVA test we observed
      the test is significant (F = 20.79, P < 0.01) and the test is rejected. When the
      Tukey's t-test result was applied it was seen that the mean shear bond strength
      of all groups of brackets is as follows: Group I (5.31 Megapascals [Mpa]) < Group
      II (7.37 Mpa) < Group III (8.96 Mpa) < Group IV (5.56 Mpa) < Control group (9.24
      Mpa). Alternatively we can say that shear bond strength of following bracket
      groups can be arranged as Group I < Group IV < Group II < Group III. CONCLUSION:
      From this study we conclude that Group III, which was recycled with an ultrasonic
      cleaner with electropolisher and silane coupling agent in place of primer, showed
      the highest shear bond strength.

PMID- 25395786
TI  - Comparison of Impact Strength and Fracture Morphology of Different Heat Cure
      Denture Acrylic Resins: An In vitro Study.
AB  - BACKGROUND: The fracture of acrylic resin denture is rather common occurrence and
      causes inconvenience to the patients. This study was carried out to evaluate and
      compare the impact strength and fracture morphology of four different heat cure
      acrylic materials. MATERIALS AND METHODS: Acrylic resin specimens were prepared
      using preformed metal die of dimension 65 * 10 * 3 mm. The specimens were
      finished, polished and subjected to impact strength evaluation using impact
      testing machine. The loads at which the specimens fracture are recorded and
      subjected to statistical analysis. Fracture surface analysis was done.
      Macroscopic analysis was performed by visual inspection of the fractured surfaces
      using a stereoscopic microscope. About 5 mm sections of all the fragments were
      subjected to scanning electron microscopy for microscopic analysis to verify
      fracture morphology. RESULTS: Mean values of the impact strength were compared by
      statistical methods. The impact strength data were subjected to variance
      homogeneity tests. Fracture surface analysis data was analyzed by statistical
      methods. The mean impact strength of Lucitone 199 was higher than Acrylyn-H, DPI
      Heat cure & Trevalon. CONCLUSION: Within the limitations of this study, it was
      concluded that the impact strength of the acrylic resins is affected by the
      reinforcement of fibers. Increased intermediate fractures increased impact
      strength. Brittle fractures morphology showed fewer undercuts and clearer
      surface. Intermediate fractures morphology showed more undercuts than clear
      surfaces.

PMID- 25395787
TI  - Ctla-4 gene polymorphism in +49 a/g position: a case control study on patients
      with oral lichen planus.
AB  - BACKGROUND: Oral lichen planus (OLP) is a premalignant mucocutaneous disease in
      which genetic factors and immune responses play a major role. Cytotoxic T
      Lymphocyte Antigen-4 (CTLA-4) is a co-inhibitory molecule that down-regulates
      immune responses to prevent autoimmunity. This study aimed to investigate the
      relationship between polymorphism of the CTLA-4 gene in +49 A/G position and OLP.
      MATERIALS AND METHODS: Thirty-five patients with OLP (16 males, 19 females, with
      a mean age of [+/- standard deviation (SD)] 55.92 [+/- 12.83]) and 105 sex- and
      aged-matched healthy subjects (48 males, 57 females, with a mean age of [+/- SD]
      56.82 [+/- 14.71]) were recruited in this study. Genomic DNA of both groups was
      extracted from white blood cells and then CTLA-4 genotypes and allele frequencies
      were investigated using polymerase chain reaction-restriction fragment length
      polymorphism methods. The data were collected and examined using Pearson's Chi
      square test (SPSS version 11.5). RESULTS: In the patient group, AA, AG, and GG
      genotypes occurred in position 49 A/G in the CTLA-4 gene with the frequency of 19
      (55.9%), 11 (31.4%), and 3 (8.8%), respectively. With respect to the control
      group, they occurred with the frequency of 58 (55.2%), 39 (37.1%), and 8 (7.6%),
      respectively. As far as the frequency of A and G alleles in this position was
      concerned, we had, respectively, 49 (74.24%) and 17 (25.75%) for patients and,
      respectively, 155 (73.80%) and 55 (26.19%) for the control group. The calculated
      values were not significantly different between these groups (P > 0.05).
      CONCLUSION: Polymorphisms of CTLA-4 genes in position +49 A/G did not show any
      significant relationship with each other in OLP patients in Shiraz, Iran.

PMID- 25395788
TI  - Tobacco Usage and Attitude towards Tobacco Cessation among Prisoners in India - A
      Cross Sectional Survey.
AB  - BACKGROUND: Tobacco is a highly addictive substance. Tobacco usage is considered
      one of the main causes responsible for the death of adults worldwide, with 4.9
      million deaths occurring worldwide each year. And if the current tobacco usage
      patterns continue, it will cause some 10 million deaths every year by 2020.
      MATERIALS AND METHODS: A descriptive study was carried out among 566 prisoners of
      central prison Bangalore, who met the inclusion criteria. Data were collected
      using a questionnaire and nicotine dependence was assessed using fagerstrom
      questionnaire. RESULTS: The study group was categorized based on the age, gender,
      imprisonment status and education. In this study, 87.5% subjects were smokers,
      and 15.9% were smokeless tobacco users. 69.1% mentioned they use more tobacco
      daily during incarceration than at liberty. 87.1% agreed with the fact that
      "prison stress" was a factor enhancing the need for tobacco usage. 69.1%
      mentioned as lack of freedom, 77.4% mentioned boredom as factors enhancing need
      for tobacco usage while imprisoned. While 69.9% mentioned stress as a factor that
      trigger tobacco usage at liberty. 69.6% mentioned that they had never attempted
      to quit tobacco. Fagerstrom scale for level of nicotine dependence smoking showed
      that for smoking form 62.7% were at very high dependence and for smokeless form
      64.4% were at very high dependence. CONCLUSION: The findings of this study
      suggest many implications for policy relevance, since the findings indicate the
      sales of tobacco products in the prison canteens.

PMID- 25395789
TI  - Dental caries and its relationship to malocclusion in permanent dentition among
      12-15 year old school going children.
AB  - BACKGROUND: This study aimed to know the prevalence of dental caries among
      children having malocclusion. MATERIALS AND METHODS: This cross-sectional study
      included 880 students aged 1215 years, among whom 488 were boys and 392 were
      girls. A proforma was prepared to record dental caries status and dental esthetic
      index (DAI) using the WHO Oral Health Assessment Form (1997). Data were analyzed
      using Student's t-test and ANOVA. The P value of 0.05 or less was considered as
      statistically significant. RESULTS: It was found that 644 (73.2%) had no
      abnormality or minor malocclusion, whereas 115 (13.0%), 100 (11.4%) and 21 (2.4%)
      had definite, severe and very severe or handicapping malocclusion, respectively.
      Overall mean of decayed teeth (DT) component was found to be 0.95 +/- 1.006,
      missing teeth 0.23 +/- 0.670 and filled teeth 0.23 +/- 0.559 and decayed,
      missing, filled tooth (DMFT) was 1.41 +/- 1.483. DT and overall DMFT component
      significantly increased with increasing DAI of malocclusion (P <= 0.05).
      CONCLUSION: The severity of dental caries showed positive relation with DAI and
      age.

PMID- 25395790
TI  - Post-retention Development of Curve of Spee in Pre-adjusted Edgewise Appliance
      Cases, Its Correlation to Dentoskeletal Parameters: An In vitro Study.
AB  - BACKGROUND: Curve of Spee was first described by Ferdin and Graf Von Spee in
      1890. The curve of Spee is an important characteristic of the mandibular dental
      arch. One of the most frequently encountered problems in the treatment of
      orthodontic patients is an excessive overbite. Deep bite has been found to be
      associated with abnormal mandibular function. Temporomandibular joint disorders
      also have potentially detrimental effects on mandibular development. Andrews
      advocated leveling the curve of Spee to aflat curve, in order to facilitate
      construction of an optimal occlusion and that a flat plane should be given as a
      form of over treatment. There is no reliable information currently available from
      the literature about the long-term stability of the curve of Spee and the factors
      influencing the same. The objective of this study was to assess the post
      retention development of the curve of Spee and to evaluate the dental and
      skeletal parameters as predictors of its post-retention stability. MATERIALS AND
      METHODS: Pre-treatment (Tl), post-treatment (T2) and post-retention (T3) dental
      casts and lateral cephalograms of 24 orthodontically treated patients having a
      mean age of 14.5 years were evaluated. The mean period of the study group after
      retention was up to 2.6 years (range = 1-5 years). Pre-treatment T1, post
      treatment T2, and post-retention T3 casts and radiographs were measured. The data
      were tabulated and statistically analyzed. RESULTS: A highly significant positive
      correlation was observed between the changes in the curve of Spee during
      treatment (T2-T1) and the net result after retention (T3-T2). This means that
      much of the treatment results remained stable at T3. However, slight change was
      noticed in curve of Spee's depth during the time interval T3-T2. This finding was
      very negligible and was not statistically significant. CONCLUSION: The leveling
      of the curve of Spee during the treatment is a stable treatment objective on long
      term basis. There was a mild correlation existing between the curve of Spee and
      the different dental and skeletal parameters.

PMID- 25395791
TI  - A comparison of hand wrist bone analysis with two different cervical vertebral
      analysis in measuring skeletal maturation.
AB  - BACKGROUND: Skeletal maturation is an integral part of individual pattern of
      growth and development and is a continuous process. Peak growth velocity in
      standing height is the most valid representation of the rate of overall skeletal
      growth. Ossification changes of hand wrist and cervical vertebrae are the
      reliable indicators of growth status of individual. The objective of this study
      was to compare skeletal maturation as measured by hand wrist bone analysis and
      cervical vertebral analysis. MATERIALS AND METHODS: Hand wrist radiographs and
      lateral cephalograms of 72 subjects aged between 7 and 16 years both male and
      female from the patients visiting Department of Orthodontics and Dentofacial
      Orthopedics, R.V. Dental College and Hospital. The 9 stages were reduced to 5
      stages to compare with cervical vertebral maturation stage by Baccetti et al. The
      Bjork, Grave and Brown stages were reduced to six intervals to compare with
      cervical vertebral maturational index (CVMI) staging by Hassel and Farman. These
      measurements were then compared with the hand wrist bone analysis, and the
      results were statistically analyzed using the Mann-Whitney test. RESULTS: There
      was no significant difference between the hand wrist analysis and the two
      different cervical vertebral analyses for assessing skeletal maturation. There
      was no significant difference between the two cervical vertebral analyses, but
      the CVMI method, which is visual method is less time consuming. CONCLUSION:
      Vertebral analysis on a lateral cephalogram is as valid as the hand wrist bone
      analysis with the advantage of reducing the radiation exposure of growing
      subjects.

PMID- 25395792
TI  - Long term stability and relapse following mandibular advancement and mandibular
      setback surgeries: a cephalometric study.
AB  - BACKGROUND: The aim was to evaluate the long-term hard and soft tissue changes
      following mandibular advancement and setback surgeries. MATERIALS AND METHODS: A
      total of 16 subjects each were selected who underwent bilateral sagittal split
      osteotomy mandibular advancement and mandibular setback groups. Pre-surgical
      (T1), immediate post-surgical (T2) and long-term post-surgical (T3) cephalograms
      were compared for hard and soft tissue changes. After cephalometric measurements,
      the quantity of changes between T1-T2 and T1-T3 were determined for each patient.
      The mean difference between T1-T2 and T1-T3 was compared with assess the long
      term changes and stability. RESULTS: In mandibular advancement the mean
      difference between immediate post-surgical and long term post-surgical is 7%,
      which accounts for a relapse of 7%. In mandibular setback, the mean difference
      between immediate post-surgical and long-term post-surgical is 29%, which
      accounts for a relapse of 29%. CONCLUSION: Mandibular advancement remained stable
      over the long period when compared to mandibular setback.

PMID- 25395793
TI  - Cuspal movement and microleakage in premolar teeth restored with posterior
      restorative materials.
AB  - BACKGROUND: With the increase in various resin-based composites with varying
      monomeric formulations and fi llers had led to a significant number of problems,
      and one of such is postoperative pain. Clinician is in a dilemma what to select
      and what not to. The latest nanocomposite is there for a short while that no
      individual research is available currently, hence, this study was undertaken. The
      aim of this present study was to assess the cuspal deflection at each stage of
      polymerization for the incremental restoration of standardized large (mesio
      occlusal distal [MOD]) cavities with three posterior restorative resins. And also
      to assess the cervical microleakage. MATERIALS AND METHODS: 18 extracted upper
      premolar teeth were selected. Teeth were divided into three groups (A, B, and C),
      each group consisting six teeth, large (MOD) cavity preparation was done. Groups
      A, B, and C were restored with P60, Filtek supreme (3M, ESPE), and ormocer
      material (Admira:Voco). The lingual cusps of the extracted teeth were
      approximated to the receptor of a compactor - deflection measuring gauge,
      following each stage of polymerization using light emitting diode curing light a
      measurement of the cuspal deflection was recorded. The restored teeth were
      prepared for microleakage testing and were examined under stereomicroscope at *25
      for the extent of the cervical gingival microleakage. RESULTS: The cuspal
      deflection was the greatest for Filtek P60 and least for filtek supreme -
      nanocomposite with ormocer ranked between the two. For the microleakage, none of
      the materials were identified as producing less gingival microleakage.
      CONCLUSION: The lesser cuspal deflection values with filtek supreme nanocomposite
      could be due to resin chemistry and also filler particle size. Hence, this
      nanocomposite could be the first choice of material for use in large esthetic
      restorations.

PMID- 25395794
TI  - Soft tissue cephalometric norms for central India (malwa) female population.
AB  - BACKGROUND: The various soft tissue traits that contribute to an aesthetically
      pleasing face. This should be considered during orthodontic treatment. The aim of
      the present study was to propose soft tissue norms for Central Indian (Malwa)
      female population. MATERIALS AND METHODS: Facial photographs of 78 patients of
      age group 18-26 years were taken in Department of Orthodontics, Rau, Indore,
      which were then subjected to a selection process and 30 top scorers (30 females)
      were selected. Lateral cephalograms of individuals were taken and soft tissue
      profile as well as related osseous and dental structures standard tracing were
      made on the acetate matte tracing paper. Then eighteen soft tissue traits were
      studied as described by Bergman. RESULTS: The present study showed that, a mild
      convexity of the face and the resulting tendency toward Class II in females is
      acceptable esthetically. A fuller upper lip is considered balanced and esthetic.
      Increase in lip incompetency is considered unaesthetic. CONCLUSION: A mild
      convexity of the face and the resulting tendency toward Class II in females is
      acceptable esthetically. Individual norms are necessary for a population in order
      to plan and deliver quality treatment.

PMID- 25395795
TI  - The Comparative Evaluation of Antibacterial Activity of Methacryloxydodecyl
      Pyridinium Bromide and Non-methacryloxydodecyl Pyridinium Bromide Dentin Bonding
      Systems Using Two Different Techniques: An In vitro Study.
AB  - BACKGROUND: Adhesive systems have enabled clinicians to preserve more tooth
      structure by changing cavity designs. However, because of the polymerization
      shrinkage adhesive systems are not capable of totally prohibiting the gap
      formation between the cavity and restorative material of composite resin leading
      to colonization of oral microorganisms from saliva. One possible solution for
      this serious problem is to use dental materials with antibacterial properties. So
      the development of such agents has initiated for successful restorations. Hence,
      the purpose of this study was to compare the antibacterial activities of two
      dentin bonding systems: Clearfil protect bond (CPB) and prime & bond NT using
      agar well technique and tooth cavity model. MATERIALS AND METHODS: CPB and prime
      and bond NT (PBNT) were evaluated in this study using agar well technique and
      tooth cavity model. In the agar well technique, the materials were filled in the
      wells of Muller-Hinton agar plates inoculated with Streptococcus mutans NCTC
      10449M and the diameter of inhibition zones produced around the materials were
      measured after 24 h of incubation. For the tooth cavity model test, 3 cavities
      (of diameter - 1 mm and depth - 2 mm) were prepared in the flat occlusal dentin
      of human extracted molar. After sterilization, the teeth were left in the culture
      of broth of S. mutans at 37 degrees C for 72 h for allowing bacteria to invade
      the cavity for 72 h. The dentin bonding systems were applied separately to each
      of the two infected cavities, and the third cavity was not applied and used as
      control. After sealing the occlusal surfaces, the teeth were kept in sterile
      physiological saline at 37 degrees C for 72 h. The standardized amounts of dentin
      chips (120 + 5 mg) were obtained from the cavity walls, and the numbers of
      bacteria recovered were determined. The results were analyzed using one-way
      ANOVA, Kruskal-Wallis and Mann-Whitney's U-tests. RESULTS: The primer of CPB and
      PBNT produced similar inhibition zones (P > 0.05), but the bonding resin of CPB
      did not produce any inhibition. When tested by the tooth cavity model technique,
      the application of CPB resulted in significantly less bacterial recovery than the
      PBNT (P < 0.05), demonstrating substantial antibacterial effects. CONCLUSION: The
      CPB that employs the antibacterial primer containing methacryloxydodecyl
      pyridinium bromide, was effective in inactivating the bacteria in the cavity
      compared to little antibacterial activity shown by PBNT. The tooth cavity mode
      test used in the present study is a reliable method to evaluate the antibacterial
      effects of dentin bonding agents simulating clinical situations.

PMID- 25395796
TI  - Comparative Evaluation of Friction Resistance of Titanium, Stainless Steel,
      Ceramic and Ceramic with Metal Insert Brackets with Varying Dimensions of
      Stainless Steel Wire: An In vitro Multi-center Study.
AB  - BACKGROUND: The orthodontist seeks an archwire-bracket combination that has both
      good biocompatibility and low friction. Hence, the aim of this multicenter in
      vitro study was to evaluate and compare the frictional resistance generated
      between titanium (Ti), stainless steel (SS), ceramic and ceramic with metal
      insert (CMI) brackets with SS wires of varying dimensions in a specially designed
      apparatus. MATERIALS AND METHODS: The material used in this study were Ti, SS,
      Ceramic and CMI with 0.018" slot manufactured with zero degree tip and -7 degrees
      torque premolar brackets (3M, Unitek) and SS wires of varying dimensions (0.016"
      round, 0.016 * 0.016" square, 0.016 * 0.022" rectangular and 0.017 * 0.025"
      rectangular) used. The frictional resistance was measured using Instron Universal
      testing machine (Model no. 4301). The specimen population in each center composed
      each of 160 brackets and wires. Differences among the all bracket/wire
      combinations were tested using (one-way) ANOVA, followed by the student Newman
      Keuls multiple comparisons of means ranking (at P < 0.05) for the determination
      of differences among the groups. RESULTS: Ti bracket in combination with 0.017 *
      0.025" SS rectangular wire produced significant force levels for an optimum
      orthodontic movement with least frictional resistance. CONCLUSION: Ti brackets
      have least resistance and rectangular wires produced significant force. These can
      be used to avoid hazards of Nickel. SS brackets revealed higher static frictional
      force values as the wire dimension increased and showed lower static friction
      than Ti brackets for all wires except the thicker wire. Our study recommends the
      preclusion of brackets with rough surface texture (Ti brackets) with SS ligature
      wire for ligating bracket and archwire are better to reduce friction.

PMID- 25395797
TI  - Comparative Evaluation of Microshear Bond Strength of 5(th), 6(th) and 7(th)
      Generation Bonding Agents to Coronal Dentin Versus Dentin at Floor of Pulp
      Chamber: An In vitro Study.
AB  - BACKGROUND: Lack of seal and adhesion between the final restoration and tooth
      structure adversely affects the results of root canal treatment. Lots of adhesive
      bonding agents are marketed to overcome this deficiency and achieve successful
      restoration. So the study compares and evaluates the micro shear bond strength of
      coronal dentin and pulp chamber dentin using three different generation dentin
      bonding systems and to know clinical efficiency for clinical use. MATERIALS AND
      METHODS: DIFFERENT GENERATION DENTIN BONDING SYSTEMS USED WERE: (1) One bottle
      total etch system (XP Bond-5(th) generation), (2) Two-step self-etch system
      (Clearfil SE Bond-6(th) generation) and (3) All-in-one system (G Bond-7(th)
      generation). Thirty human mandibular molars were collected out of which sixty
      samples were prepared by sectioning each tooth into coronal dentin and pulpal
      floor dentin. They were divided into two major groups. Group I: 30 Coronal dentin
      samples. Group II:30 Pulpal floor dentin samples. Both the groups were further
      subdivided depending on the bonding agent used. Subgroup Ia:XP Bond, Subgroup
      Ib:Clearfil SE Bond, Subgroup Ic:G Bond, Subgroup IIa:XP Bond, Subgroup
      IIb:Clearfil SE Bond, Subgroup IIc:G Bond. Resin composite was bonded to these
      samples and tested for micro-shear bond strength. The mean bond strengths and
      standard deviations were calculated and analyzed using one-way ANOVA test and
      Student's t-test (unpaired) and honestly significant difference post-hoc tests.
      RESULTS: Coronal dentin showed higher values of micro shear bond strength than
      the pulpal floor dentin. All-in-one system (G Bond) showed least bond strength
      values to both the regions coronal dentin and pulpal floor dentin. CONCLUSION:
      Factors affecting the shear bond strength are dependent on material (adhesive
      system), substrate depth and adhesive/depth interaction. Hence composition and
      substrate treatment should be considered for good adhesive. Chemical composition
      of adhesive system determines clinical successes.

PMID- 25395798
TI  - The comparison of oral health problems with other health problems in urban school
      children of 10-14 years: a group screening.
AB  - BACKGROUND: The overall health, well-being, education, learning abilities,
      development of children, families, and communities can be affected by oral
      health. However in the developing nations, the importance of oral health in
      comparison to general health is minimal. The objective was to evaluate and
      compare the oral health problems in relation to general health problems of the
      same children by a group screening method. MATERIALS AND METHODS: A total of 592
      children in the age group of 10-14 years were selected from class 6 to 10, the
      focus initially was on general health screening, vision screening, oral health
      screening, tonsillar, and auditory screening of students. Among these children,
      296 individuals were apparently healthy with no undiagnosed health aliments; the
      remaining children were having some health problems. Statistical analysis was
      performed using paired t-test. RESULTS: About 50% of children were apparently
      healthy, 19.9% had oral health problems, which was considerably higher than other
      health problems. The general health problems were 15.20%. CONCLUSION: By
      conducting such a study, we can know that the awareness and identification of
      other health problems are in urban school children is higher than the oral health
      problems. This recommends promoting awareness on the oral health and importance
      of regular dental check-up in children.

PMID- 25395799
TI  - A clinical study of efficacy of 4% articaine hydrochloride versus 2% lignocaine
      hydrochloride in dentistry.
AB  - BACKGROUND: Articaine in an anesthetic agent, which is used less frequently in
      dentistry. It differs from other agents due to the presence of a thiophene ring
      in its molecular structure. Few groups of researchers claim that it is superior
      to lignocaine. Hence, the purpose of this study was to compare the efficacy of 4%
      articaine hydrochloride and 2% lignocaine hydrochloride in the orthodontic
      extraction. MATERIALS AND METHODS: The study was carried out in 50 patients who
      needed the orthodontic extraction in the age group from 15 to 25 years.
      Experimental sites were injected with 0.5-1 ml of 4% articaine HCL containing
      1:100000 adrenaline, incrementally in the buccal vestibule without palatal
      anaesthesia. Control sites were injected with 0.8-1 ml of 2% lignocaine HCL
      containing 1:100000 adrenaline, incrementally in the buccal vestibule. All the
      parameters, that is volume, duration, time of anesthesia and pain rating were
      noted and statistically compared. RESULT: When statistically compared mean volume
      of articaine (0.779 +/- 0.1305) was less than lignocaine (1.337 +/- 0.2369). Mean
      time of onset of articaine was 1.012 +/- 0.2058 min, Whereas that of was 1.337 +/
      0.2369. Pain rating showed not much difference, but in the lignocaine group
      palatal anesthesia was required in all the patients. Finally, the mean duration
      of anesthesia in articaine group was 69.08 +/- 18.247, whereas in the lignocaine
      group was 55.66 +/- 6.414. CONCLUSION: Articaine has proved its usefulness in all
      regards. Literatures have proved its usefulness. Like other anesthetic, it is
      safe and more effective. It surpasses the need of additional palatal anesthesia.
      Rapid inactivation in liver and plasma reduces the risk of the drug overdose. All
      the above factors make it an ideal anesthetic agent to be used in dentistry.

PMID- 25395800
TI  - An In vitro Study on Post Bleaching Pigmentation Susceptibility of Teeth and
      Scanning Electron Microscopy Analysis.
AB  - BACKGROUND: To determine the susceptibility of teeth for repigmentation after
      bleaching. MATERIALS AND METHODS: Forty premolars were assigned to three groups
      (n = 12). Group 1 was bleached using 30% w/v hydrogen peroxide 15 min 3 times a
      day every other day for 4 days. In Group 2 was bleached using 16% carbamide
      peroxide (Polanight), 90 min a day for 15 days. 2 days later, the shades of the
      bleached teeth were recorded. Remaining 4 teeth were bleached according to Group
      1 and 2 and were subjected to atomic force microscopy, scanning electron
      microscopy analysis. RESULTS: Specimens of athome bleaching were lighter than the
      specimens of inoffice bleaching. CONCLUSION: The susceptibility of enamel to
      pigmentation can be increased after bleaching, and pigmentation is greater if
      bleaching is performed with H2O2. The percentage change (lighter) was more for
      athome bleaching specimens as compared to inoffice bleaching specimens.

PMID- 25395802
TI  - In vitro Evaluation of Antibacterial Efficacy of Pineapple Extract (Bromelain) on
      Periodontal Pathogens.
AB  - BACKGROUND: Periodontitis is an inflammatory disease resulting in the destruction
      of periodontal tissues. Various treatment modalities have been tried in the form
      of mechanical therapy and surgical therapy. Antimicrobial agents have been used
      as a monotherapy and as an adjunct with mechanical debridement. Various plant
      extracts have been used as antibacterial agents. Pineapple extract (bromelian) is
      one such agent. Hence this study was conducted to assess the antibacterial
      efficacy of bromelain on both aerobic and anaerobic periodontal microorganisms.
      The aim was to assess the antibacterial efficacy of bromelain on both aerobic and
      anaerobic periodontal microorganisms. MATERIALS AND METHODS: Minimum inhibitory
      concentration (MIC) of bromelain was tested on isolated strains of Streptococcus
      mutans, Enterococcus fecalis Aggregatibacter actinomycetemcomitans (Aa), and
      Porphyromonas gingivalis (Pg) using serial dilution broth method. RESULTS: S.
      mutans showed sensitivity at the lowest concentration of 2 mg/ml as compared to E
      fecalis (31.25 mg/ml) while Pgingivalis showed sensitivity at the lowest
      concentration of 4.15 mg/ml as compared to Aa (16.6 mg/ml). CONCLUSION: Bromelain
      exerts an antibacterial effect against potent periodontal pathogens; hence, it
      may be used as an antibacterial agent. However, further trial has to be conducted
      to validate this result.

PMID- 25395801
TI  - Palatal rugae patterns in orthodontically treated cases, are they a reliable
      forensic marker?
AB  - BACKGROUND: The specialization of forensic odontology is fast emerging as a
      branch that helps in personal identification of both living as well as dead
      individuals and also in crime scene investigations. Establishing a person's
      identity can be a challenging task in cases of road accidents or acts of
      terrorism or mass disaster scenario. It is an established fact that palatal rugae
      are unique for each individual and can be reliably used in the forensic field for
      personal identification. The present study was undertaken to evaluate the post
      treatment stability of palatal rugae pattern in individuals subjected to
      orthodontic treatment with and without extractions and palatal expansion.
      MATERIALS AND METHODS: A total of 137 pre- and post-orthodontically treated casts
      of patients were obtained from our institute, which were divided into 50 cases
      each of extraction and non-extraction, 37 cases of palatal expansion involving
      both extraction and non-extraction. Palatal rugae patterns of all the cases were
      compared pre- and post-treatment. RESULTS: Chi-square test was applied for
      comparison of changes with respect to shape of rugae patterns. Maximum changes
      were seen in palatal expansion and extraction group and minimum changes in non
      extraction group both on right and left sides. All three groups were compared
      involving all three parameters by Chi square test. About 89.19% and 84% of the
      study group showed changes in palatal expansion and extraction cases
      respectively. Although, a 62% of study subjects showed changes in non-extraction
      group with a P = 0.00041. CONCLUSION: Orthodontic treatment has an impact on the
      stability of palatal rugae so investigator should be aware of this fact when
      analyzing for identification reasons.

PMID- 25395803
TI  - Comparative Evaluation of Metal-ceramic Bond Strengths of Nickel Chromium and
      Cobalt Chromium Alloys on Repeated Castings: An In vitro Study.
AB  - BACKGROUND: Recasting the base metal alloys is done as a routine procedure in the
      dental laboratories whenever there is casting failure or to decrease the unit
      cost of a fixed partial denture. However, this procedure may affect the metal
      ceramic bond. Furthermore, it is unclear, as to which test closely predicts the
      bond strength of metal-ceramic interface. The aim was to compare the bond
      strength of nickel chromium (Ni-Cr) and cobalt chromium (Co-Cr) alloys with
      dental ceramic on repeated castings using shear bond test with a custom made
      apparatus. MATERIALS AND METHODS: Sixty metal ceramic samples were prepared using
      Wiron 99 and Wirobond C, respectively. Three subgroups were prepared for each of
      the groups. The first subgroup was prepared by casting 100% fresh alloy. The
      second and third subgroups were prepared by adding 50% of fresh alloy and the
      remnants of the previous cast alloy. The bond load (N) between alloy and dental
      porcelain was evaluated using universal testing machine using a crosshead speed
      of 1 mm/min, which had a 2500-kgf load cell. Mean values were compared using
      oneway analysis of variance with post-hoc Tukey's test and Student's t-test.
      RESULTS: The mean shear bond load of A0 (842.10N) was significantly higher than
      the load of A1 (645.50N) and A2 (506.28N). The mean shear bond load of B0
      (645.57N) was significantly higher than the load of B1 (457.35N) and B2
      (389.30N). CONCLUSIONS: Significant reduction in the bond strength was observed
      with the addition of the first recast alloy (A1 and B1) compared with the
      addition of second recast alloy (A2 and B2). Ni-Cr alloys (664.63N) showed higher
      bond strengths compared to that of Co-Cr alloys (497.41N). The addition of
      previously used base metal dental alloy for fabricating metal ceramic
      restorations is not recommended.

PMID- 25395804
TI  - Delayed reimplantation: a case report.
AB  - A 12-year-old boy reported to the clinic with a history of trauma, whereas
      playing 1 day before. On examination it was noted that the patient had an avulsed
      tooth in relation to 11, Class III fracture in relation to 12 and Class II
      fracture in relation to 21. The avulsed tooth was brought by the patient wrapped
      in a newspaper. Although the tooth was in highly unfavorable storage condition,
      it was decided to reimplant the teeth since the patient was young and to relieve
      him from psychological, cosmetic and functional trauma. Now after 24 months, the
      tooth is, functional, firm and free of symptoms with minimal signs of resorption.
      Even though the long-term prognosis is uncertain, this treatment technique has
      proven to be an advantage for the patient in this growing period by maintaining
      the esthetics, by maintaining the height of alveolar bone and making the
      provision of an aesthetically acceptable permanent restoration at a later age if
      prognosis becomes poor. 

PMID- 25395805
TI  - Juvenile aggressive ossifying fibroma of the maxilla: a case report.
AB  - Juvenile ossifying fibroma is an uncommon fibro osseous neoplasm at a younger
      age. It is a well-defined clinical and histological lesion. This lesion is
      locally invasive and spreads quickly. Early detection and complete surgical
      excision of this lesion is essential since it has high recurrence rate. 

PMID- 25395806
TI  - Using an existing crown to repair a damaged cast post and core restoration.
AB  - A fractured coronal tooth structure beneath an intact crown is a common clinical
      occurrence. If the underlying root is healthy, the tooth is restored with a post
      and core followed by refabrication of the crown. This paper describes a technique
      of using the existing intact crown for the above-mentioned situation. A 34-year
      old female was referred with a fractured right canine with an intact crown. A
      post was found fractured in the canal which was subsequently retrieved. A new
      fiber post was cemented in the post space followed by adaptation of 50 MUm
      polytetrafluoroethylene (teflon) tape on the tissue surface of the crown. Dual
      cured core build-up composite resin was injected into the crown and adapted to
      the fractured tooth. On curing and removal of the crown, a new composite resin
      core was found bonded to the tooth structure. The Teflon tape was removed from
      the crown, and the crown cemented to the core using glass ionomer cement. This
      technique of building up the core of the tooth using teflon tape adapted to the
      tissue surface of the crown was found to be successful even after 1 year of
      follow-up. 

PMID- 25395807
TI  - A labially positioned mesiodens and its repositioning as a missing central
      incisor.
AB  - Hyperdontia is an increased number of teeth within the dental arches. This is of
      particular interest to pediatric dentists who commonly make the initial
      diagnosis. Most often a large portion of these teeth is completely embedded or
      impacted within the jaws and can be viewed only radiographically. Hyperdontia can
      occur on virtually every tooth-bearing surface. However, the most frequent is the
      mesiodens, in the anterior maxillary region. Anterior maxillary teeth are one of
      the most important features contributing to aesthetics of an individual. Missing
      anterior teeth can cause undue psychological stress in children, during their
      growing years. Most of the literature available show that the mesiodens are
      situated on the palatal aspect of the permanent incisors. Their treatment
      frequently involves an early recognition, extraction through a traditional
      palatal technique and guiding the associated permanent tooth to its original
      position. The purpose of this article is to enlighten the clinician of the need
      of deviating from the traditional approach of early extraction in particular
      situations and to conserve the mesiodens if favorable as an alternative treatment
      to a malformed permanent tooth, which may fail to erupt. This report describes a
      successful multidisciplinary approach to treatment of a unerrupted, labially
      placed mesiodens in conjunction with a dilacerated and impacted permanent tooth,
      in a child with a missing left central incisor. Treatment consisted of localizing
      and confirming the placement of the mesiodens to be labial, surgically exposing
      the crown of the mesiodens through a labial surgical approach, orthodontically
      guiding it to the position of the missing central incisor, extracting the
      malformed permanent incisor, and restoring the mesiodens to the required anatomy
      with composites, to establish aesthetics and function of the affected region. 

PMID- 25395808
TI  - Chromosomal and multifactorial genetic disorders with oral manifestations.
AB  - The chromosomal disorders are individually rare, but collectively they are common
      whereas the multifactorial disorders are the most common form of genetic
      disorders. The chromosomal anomalies typically arise from alterations in the DNA
      containing chromosomal regions and can be reliably detected by karyotype
      analysis, whereas the multifactorial disorders demonstrate multi-gene as well as
      environmental interactions. Both the chromosomal and multifactorial disorders may
      manifest signs and symptoms such as a combination of birth defects, physical
      disabilities, challenging behavior and certain craniofacial defects as well, the
      knowledge of which can aid in a better patient management in everyday practice of
      dentistry. 

PMID- 25395810
TI  - Retraction notice.

PMID- 25395811
TI  - Oral Cancer: Early Detection is Crucial.

PMID- 25395809
TI  - Oral fluid-based biomarkers in periodontal disease - part 2. Gingival crevicular
      fluid.
AB  - Periodontal diagnosis and treatment plan are based on the assessment of probing
      depth, clinical attachment level, plaque index, gingival index, bleeding on
      probing, suppuration, furcation involvement, mobility, and radiographic findings.
      However, these clinical parameters are not sufficiently sensitive and specific to
      identify disease activity in individual sites or to predict future attachment
      loss. Hence, attention is focused on the development of diagnostic tools that
      could screen and differentiate the active inflamed sites and predict future
      tissue destruction. Gingival crevicular fluid (GCF), has gained great interest on
      possible diagnostic value in periodontal disease. It contains a large number of
      proteins and peptides derived from inflamed host tissues. The analysis of the GCF
      components can reflect the disease status of individual sites and thus, identify
      potential biomarkers of periodontitis. A literature search was carried out to
      find out all the available tests that indicate periodontal disease markers in
      GCF. All major databases were searched to compile the information on published
      reports between 1999 and 2014. The list of GCF-biomarkers available to date is
      compiled and presented in a table format. Based on the available literature on
      GCF biomarkers, it can be concluded that several sensitive and reliable markers
      are present to detect the presence, severity, and response to treatment. Further
      studies are warranted to analyze the sensitivity and reliability of these
      indicators which might help in developing noninvasive tests that could help in
      the diagnosis of periodontal disease. 

PMID- 25395812
TI  - Simulation Evaluation of Quantitative Myocardial Perfusion Assessment from
      Cardiac CT.
AB  - Contrast enhancement on cardiac CT provides valuable information about myocardial
      perfusion and methods have been proposed to assess perfusion with static and
      dynamic acquisitions. There is a lack of knowledge and consensus on the
      appropriate approach to ensure 1) sufficient diagnostic accuracy for clinical
      decisions and 2) low radiation doses for patient safety. This work developed a
      thorough dynamic CT simulation and several accepted blood flow estimation
      techniques to evaluate the performance of perfusion assessment across a range of
      acquisition and estimation scenarios. Cardiac CT acquisitions were simulated for
      a range of flow states (Flow = 0.5, 1, 2, 3 ml/g/min, cardiac output = 3,5,8
      L/min). CT acquisitions were simulated with a validated CT simulator
      incorporating polyenergetic data acquisition and realistic x-ray flux levels for
      dynamic acquisitions with a range of scenarios including 1, 2, 3 sec sampling for
      30 sec with 25, 70, 140 mAs. Images were generated using conventional image
      reconstruction with additional image-based beam hardening correction to account
      for iodine content. Time attenuation curves were extracted for multiple regions
      around the myocardium and used to estimate flow. In total, 2,700 independent
      realizations of dynamic sequences were generated and multiple MBF estimation
      methods were applied to each of these. Evaluation of quantitative kinetic
      modeling yielded blood flow estimates with an root mean square error (RMSE) of
      ~0.6 ml/g/min averaged across multiple scenarios. Semi-quantitative modeling and
      qualitative static imaging resulted in significantly more error (RMSE = ~1.2 and
      ~1.2 ml/min/g respectively). For quantitative methods, dose reduction through
      reduced temporal sampling or reduced tube current had comparable impact on the
      MBF estimate fidelity. On average, half dose acquisitions increased the RMSE of
      estimates by only 18% suggesting that substantial dose reductions can be employed
      in the context of quantitative myocardial blood flow estimation. In conclusion,
      quantitative model-based dynamic cardiac CT perfusion assessment is capable of
      accurately estimating MBF across a range of cardiac outputs and tissue perfusion
      states, outperforms comparable static perfusion estimates, and is relatively
      robust to noise and temporal subsampling.

PMID- 25395813
TI  - Misadministration of IV Insulin Associated With Dose Measurement And Hyperkalemia
      Treatment.
AB  - Measuring mix-ups blamed for overdoses of insulin. 

PMID- 25395814
TI  - FDA's Proposed 503B Draft Compounding Guidance Raises Concerns of All Kinds: Is
      the Bar Being Set Too High, or Too Low?
AB  - FDA draft guidance on 503B compounding widely faulted. 

PMID- 25395816
TI  - Pharmaceutical approval update.
AB  - Naltrexone/bupropion (Contrave) for weight management; pembrolizumab (Keytruda)
      for melanoma; dolutegravir/abacavir/lamivudine (Triumeq) for HIV-1; and immune
      globulin infusion 10% (human) with recombinant human hyaluronidase (Hyqvia) for
      primary immunodeficiency. 

PMID- 25395817
TI  - Riociguat (adempas): a novel agent for the treatment of pulmonary arterial
      hypertension and chronic thromboembolic pulmonary hypertension.
AB  - Riociguat (Adempas): a novel agent for the treatment of pulmonary arterial
      hypertension and chronic thromboembolic pulmonary hypertension. 

PMID- 25395818
TI  - Medications for Parkinson's disease.

PMID- 25395819
TI  - The changing roles of p&t committees: a look back at the last decade and a look
      forward to 2020.
AB  - Market and regulatory changes in the last 10 years, as well as the Affordable
      Care Act, have resulted in significant modifications to health care delivery
      models. Traditionally, P&T committees limited the impact of their decisions to
      the populations associated with their hospital or health plan; however, as
      hospitals have begun to transform into larger health systems and even integrated
      payer organizations, P&T committees must consider both inpatient and outpatient
      needs of patients in multiple hospitals and ambulatory care settings. The
      function of the P&T committee has not necessarily changed, but its scope has
      expanded. Considerations of quality, cost (reimbursement), and access
      (accreditation) affecting P&T committees over the past decade will become even
      more important as new drugs and biotech therapies enter the market and the
      shortage of primary care physicians intensifies. Pharmacists, physical
      therapists, nurses, and physicians are assuming new leadership responsibilities,
      making them partners with P&T committees in improving clinical care and cost
      performance for health systems. 

PMID- 25395820
TI  - Epilepsy management: newer agents, unmet needs, and future treatment strategies.
AB  - Drug therapy aids most epilepsy patients, but unmet challenges include drug
      resistant epilepsy, adverse reactions, drug interactions, the need to better
      identify epileptic syndromes, and a lack of agents to prevent epilepsy and its
      comorbidities. 

PMID- 25395821
TI  - Modest growth seen in epilepsy market.
AB  - The epilepsy market's $4.2 billion in global sales in 2012 is expected to
      increase to $5.4 billion by 2022. In a market crowded with products,
      pharmaceutical companies have shifted their focus to devising safe adjunctive
      therapies for refractory patients. 

PMID- 25395822
TI  - European society of cardiology and transcatheter cardiovascular therapeutics.
AB  - In these two major cardiology meetings, the pharmacology emphasis was strong on
      balancing risks of stroke and bleeding in treating heart attacks and atrial
      fibrillation. 

PMID- 25395823
TI  - Survey reveals trends in eye care: respondents weigh in on adherence, vision
      screenings, patient support programs, and e-prescribing.
AB  - A survey on the eye care market shows areas of agreement and a few sharp
      differences among ophthalmologists, optometrists, and managed care executives. 

PMID- 25395824
TI  - Can we keep this simple, please?: The challenge of explaining manipulation to
      patients.

PMID- 25395825
TI  - Is there preliminary value to a within- and/or between-session change for
      determining short-term outcomes of manual therapy on mechanical neck pain?
AB  - OBJECTIVES: The primary purpose of this study was to determine whether
      occurrences of within- and between-session changes were significantly associated
      with functional outcomes, pain, and self-report of recovery in patients at
      discharge who were treated with manual therapy for mechanical neck pain. A
      secondary purpose was to determine the extent of change needed for the within-
      and between-session change in association to function. METHODS: This secondary
      data analysis examined 56 patients who demonstrated a positive response to manual
      therapy during the initial assessment within a randomized controlled trial (RCT)
      that examined manual therapy techniques and a home exercise program (HEP). Within
      and between-session findings were defined as 'changes in pain report during the
      initial session (within)' and 'changes in pain from baseline to 48-hours post
      initial assessment (between)'. Outcomes were analyzed for associations with the
      global rating of change (GRoC), self-report activity scale (SRAS), and a 50%
      reduction of the neck disability index (NDI) by discharge at 96 hours. RESULTS:
      Findings indicate that within-session pain changes of 36.7% are strongly
      associated with a 50% change in NDI at 96 hours. Between-session changes in pain
      were associated with 50% change in NDI and a ?3-point change in GRoC at 96 hours.
      CONCLUSION: Both within- and between-session measures may be useful to predict
      success levels at 96 hours for NDI; however, between-session changes are more
      useful to predict success in GRoC. Measures used during clinical examination may
      help guide clinicians in identification of candidates best suited for the
      treatment.

PMID- 25395826
TI  - Content and bibliometric analyses of the Journal of Manual & Manipulative
      Therapy.
AB  - BACKGROUND: Article characteristics and trends have been elucidated for other
      physical therapy-focused journals using content and bibliometric analysis. These
      findings are important for assessing the current state of a journal and for
      guiding future publication of research. To date, these analyses have not been
      performed for the Journal of Manual & Manipulative Therapy (JMMT). OBJECTIVE: To
      describe content and trends for articles published in JMMT over a 20-year period
      (1993-2012). METHODS: Journal articles were coded using previously-established
      domains (article type, participant type, research design, study purpose, and
      clinical condition). Total publications and proportion of publications based on
      domain were described. Articles specific to manual therapy intervention were
      examined and compared to data from other physical therapy-focused journals.
      Impact by citation and author was examined using bibliometric software. RESULTS:
      Journal of Manual & Manipulative Therapy was found to have a recent acceleration
      in the number of articles published annually. Over time, topical reviews have
      decreased in favor of research reports. However, rigorous study designs have
      represented only a small portion of total journal content, and case reports have
      maintained a consistent publication presence. Manual therapy intervention
      articles in JMMT are predominantly case designs, however are similar in
      characteristics to manual therapy intervention articles published in other
      physical therapy-focused journals. For JMMT articles overall and manual therapy
      intervention articles across journals, young to middle-aged symptomatic adults
      with low back and/or neck pain were the most common study participants.
      DISCUSSION: Increases in the number of papers and a move toward research reports
      were observed in JMMT over the 20-year period. Considerations for the future were
      outlined, including the publication of articles with more rigorous research
      designs. Manual therapy research for adolescents and older adults and for upper
      and lower extremity conditions should also be considered as priorities for the
      future.

PMID- 25395827
TI  - The immediate effects of thoracic transverse mobilization in patients with the
      primary complaint of mechanical neck pain: a pilot study.
AB  - OBJECTIVE: Posterior-to-anterior (PA) vertebral mobilization to the thoracic
      spine has been studied as an intervention for neck pain. Our purpose was to
      explore effects of a different mobilization technique, transverse vertebral
      pressure, on cervical range of motion (ROM) and pain when applied to the thoracic
      spine among participants with neck pain. METHODS: A single-blinded quasi
      experimental study with a one-group pretest-posttest design. A transverse group
      consisted of 21 participants whose neck pain increased with active movements. A
      non-intervention group of 20 asymptomatic participants was included simply to
      ensure rater blinding. The treatment group received Grades IV to IV+ transverse
      mobilizations at T1 through T4 bilaterally. Measurements taken immediately after
      intervention included pre/post cervical ROM, distant pressure pain threshold
      (PPT), and a numerical pain rating scale (NPRS). Analysis utilized t-tests and
      ordinal counterparts. RESULTS: The transverse group demonstrated significant
      gains in extension and bilateral rotation (P<=0.005) but not flexion or side
      bend. A total of 57% of mobilized participants reported clinically meaningful
      decreased pain (P<0.001). Seven participants exceeded the PPT MDC95 of 0.36
      kg/cm(2). The non-intervention group had no significant changes in ROM or NPRS
      scores. DISCUSSION: After 8 minutes of transverse mobilization to the upper
      thoracic spine, significant gains in cervical extension and bilateral rotation,
      and decreased pain scores were found. There were no adverse effects. Unlike other
      mobilization studies, PPT changes at a remote site were statistically but not
      clinically meaningful. Findings suggest that transverse mobilization would be a
      productive topic for controlled clinical trials.

PMID- 25395828
TI  - Inter-examiner reliability of diplomats in the mechanical diagnosis and therapy
      system in assessing patients with shoulder pain.
AB  - OBJECTIVE: To investigate the inter-examiner reliability of Mechanical Diagnosis
      and Therapy (MDT)-trained diplomats in classifying patients with shoulder
      disorders. The MDT system has demonstrated acceptable reliability when used in
      patients with spinal disorders; however, little is known about its utility when
      used for appendicular conditions. METHODS: Fifty-four clinical scenarios were
      created by a group of 11 MDT diploma holders based on their clinical experience
      with patients with shoulder pain. The vignettes were made anonymous, and their
      clinical diagnoses sections were left blank. The vignettes were sent to a second
      group of six international McKenzie Institute diploma holders who were asked to
      classify each vignette according to the MDT categories for upper extremity. Inter
      examiner agreement was evaluated with kappa statistics. RESULTS: There was 'very
      good' agreement among the six MDT diplomats for classifying the McKenzie
      syndromes in patients with shoulder pain (kappa = 0.90, SE = 0.018). The raw
      overall level of multi-rater agreement among the six clinicians in classifying
      the vignettes was 96%. After accounting for the actual MDT category for each
      vignette, kappa and the raw overall level of agreement decreased negligibly (0.89
      and 95%, respectively). DISCUSSION: Using clinical vignettes, the McKenzie system
      of MDT has very good reliability in classifying patients with shoulder pain. As
      an alternative, future reliability studies could use real patients instead of
      written vignettes.

PMID- 25395829
TI  - A comparison of two non-thrust mobilization techniques applied to the C7 segment
      in patients with restricted and painful cervical rotation.
AB  - OBJECTIVES: Cervical mobilization and manipulation have been shown to improve
      cervical range of motion and pain. Rotatory thrust manipulation applied to the
      lower cervical segments is associated with controversy and the potential for
      eliciting adverse reactions (AR). The purpose of this clinical trial was to
      describe two translatory non-thrust mobilization techniques and evaluate their
      effect on cervical pain, motion restriction, and whether any adverse effects were
      reported when applied to the C7 segment. METHODS: This trial included 30
      participants with painful and restricted cervical rotation. Participants were
      randomly assigned to receive one of the two mobilization techniques. Active
      cervical rotation and pain intensity measurements were recorded pre- and post
      intervention. Within group comparisons were determined using the Wilcoxon signed
      rank test and between group comparisons were analyzed using the Mann-Whitney U
      test. Significance was set at P = 0.05. RESULTS: Thirty participants were
      evaluated immediately after one of the two mobilization techniques was applied.
      There was a statistically significant difference (improvement) for active
      cervical rotation after application of the C7 facet distraction technique for
      both right (P = 0.022) and left (P = 0.022) rotation. Statistically significant
      improvement was also found for the C7 facet gliding technique for both right (P =
      0.022) and left rotation (P = 0.020). Pain reduction was statistically
      significant for both right and left rotation after application of both
      techniques. Both mobilization techniques produced similar positive effects and
      one was not statistically superior to the other. DISCUSSION: A single application
      of both C7 mobilization techniques improved active cervical rotation, reduced
      perceived pain, and did not produce any AR in 30 patients with neck pain and
      movement limitation. These two non-thrust techniques may offer clinicians an
      additional safe and effective manual intervention for patients with limited and
      painful cervical rotation. A more robust experimental design is recommended to
      further examine these and similar cervical translatory mobilization techniques.

PMID- 25395830
TI  - Peripheral response to cervical or thoracic spinal manual therapy: an evidence
      based review with meta analysis.
AB  - OBJECTIVES: Spinal manual therapy (SMT) is commonly used for treatment of
      musculoskeletal pain in the neck, upper back, or upper extremity. Some authors
      report a multi-system effect of SMT, including peripheral alterations in skin
      conductance and skin temperature, suggesting that SMT may initiate a sympathetic
      nervous system (SNS) response. The focus of this evidence-based review and meta
      analysis is to evaluate the evidence of SNS responses and clinically relevant
      outcomes following SMT to the cervical or thoracic spine. METHODS: A SYSTEMATIC
      SEARCH USED THE TERMS: 'manual therapy', 'SMT', 'spinal manipulation',
      'mobilization', 'SNS', 'autonomic nervous system', 'neurophysiology',
      'hypoalgesia', 'pain pathophysiology', 'cervical vertebrae', 'thoracic
      vertebrae', 'upper extremity', and 'neurodynamic test'. Data were extracted and
      within-group and between-group effect sizes were calculated for outcomes of skin
      conductance, skin temperature, pain, and upper extremity range of motion (ROM)
      during upper limb neurodynamic tests (ULNTs). RESULTS: Eleven studies were
      identified. Statistically significant changes were seen with increased skin
      conductance, decreased skin temperature, decreased pain, and increased upper
      extremity ROM during ULNT. DISCUSSION: A mechanical stimulus at the cervical or
      thoracic spine can produce a SNS excitatory response (increased skin conductance
      and decreased skin temperature). Findings of reduced pain and increased ROM
      during ULNT provide support to the clinical relevance of SMT. This evidence
      points toward additional mechanisms underlying the therapeutic effect of SMT. The
      effect sizes are small to moderate and no long-term effects post-SMT were
      collected. Future research is needed to associate peripheral effects with a
      possible centrally-mediated response to SMT.

PMID- 25395831
TI  - Effect of honokiol on the induction of drug-metabolizing enzymes in human
      hepatocytes.
AB  - Honokiol, 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol, an active
      component of Magnolia officinalis and Magnolia grandiflora, exerts various
      pharmacological activities such as antitumorigenic, antioxidative, anti
      inflammatory, neurotrophic, and antithrombotic effects. To investigate whether
      honokiol acts as a perpetrator in drug interactions, messenger ribonucleic acid
      (mRNA) levels of phase I and II drug-metabolizing enzymes, including cytochrome
      P450 (CYP), UDP-glucuronosyltransferase (UGT), and sulfotransferase 2A1
      (SULT2A1), were analyzed by real-time reverse transcription polymerase chain
      reaction following 48-hour honokiol exposure in three independent cryopreserved
      human hepatocyte cultures. Honokiol treatment at the highest concentration tested
      (50 MUM) increased the CYP2B6 mRNA level and CYP2B6-catalyzed bupropion
      hydroxylase activity more than two-fold in three different hepatocyte cultures,
      indicating that honokiol induces CYP2B6 at higher concentrations. However,
      honokiol treatment (0.5-50 MUM) did not significantly alter the mRNA levels of
      phase I enzymes (CYP1A2, CYP3A4, CYP2C8, CYP2C9, and CYP2C19) or phase II enzymes
      (UGT1A1, UGT1A4, UGT1A9, UGT2B7, and SULT2A1) in cryopreserved human hepatocyte
      cultures. CYP1A2-catalyzed phenacetin O-deethylase and CYP3A4-catalyzed midazolam
      1'-hydroxylase activities were not affected by 48-hour honokiol treatment in
      cryopreserved human hepatocytes. These results indicate that honokiol is a weak
      CYP2B6 inducer and is unlikely to increase the metabolism of concomitant CYP2B6
      substrates and cause pharmacokinetic-based drug interactions in humans. 

PMID- 25395832
TI  - Functional analysis of tanshinone IIA that blocks the redox function of human
      apurinic/apyrimidinic endonuclease 1/redox factor-1.
AB  - Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a
      multifunctional protein possessing both DNA repair and redox regulatory
      activities. It has been shown that blocking redox function leads to genotoxic,
      antiangiogenic, cytostatic, and proapoptotic effects in cells. Therefore, the
      selective inhibitors against APE1's redox function can be served as potential
      pharmaceutical candidates in cancer therapeutics. In the present study, we
      identified the biological specificity of the Chinese herbal compound tanshinone
      IIA (T2A) in blocking the redox function of APE1. Using dual polarization
      interferometry, the direct interaction between APE1 and T2A was observed with a
      KD value at subnanomolar level. In addition, we showed that T2A significantly
      compromised the growth of human cervical cancer and colon cancer cells.
      Furthermore, the growth-inhibitory or proapoptotic effect of T2A was diminished
      in APE1 knockdown or redox-deficient cells, suggesting that the cytostatic effect
      of T2A might be specifically through inhibiting the redox function of APE1.
      Finally, T2A pretreatment enhanced the cytotoxicity of ionizing radiation or
      other chemotherapeutic agents in human cervical cancer and colon cancer cell
      lines. The data presented herein suggest T2A as a promising bioactive inhibitor
      of APE1 redox activity. 

PMID- 25395833
TI  - Discovery and evaluation of novel anti-inflammatory derivatives of natural
      bioactive curcumin.
AB  - Curcumin is a natural active product that has various pharmacological activities
      such as anti-inflammatory effects. Here, we report the synthesis and evaluation
      of 34 monocarbonyl curcumin analogs as novel anti-inflammatory agents. Among the
      analogs, the symmetrical heterocyclic type displayed the strongest inhibition of
      lipopolysaccharide (LPS)-stimulated expression of pro-inflammatory cytokines in
      macrophages. Analogs S1-S5 and AS29 reduced tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) production in a dose-dependent manner and also
      displayed excellent stability and low cytotoxicity in vitro. In addition, analog
      S1 dose-dependently inhibited LPS-induced extracellular signal-regulated kinase
      (ERK) phosphorylation. Furthermore, analogs S1 and S4 displayed a significant
      protective effect on LPS-induced septic death in mouse models, with 40% and 50%
      survival rates, respectively. These data demonstrate that the heterocyclic
      monocarbonyl curcumin analogs have potential therapeutic effects in acute
      inflammatory diseases. 

PMID- 25395834
TI  - The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and
      ERK1/2 phosphorylation in 6-OHDA-lesioned rats.
AB  - The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) has been used as an
      effective drug for treating dopamine depletion-induced Parkinson's disease (PD).
      However, long-term administration of L-DOPA produces motor complications. L-DOPA
      has also been found to modify the two key signaling cascades, protein kinase
      A/dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and
      extracellular signal-regulated kinases 1 and 2 (ERK1/2), in striatal neurons,
      which are thought to play a pivotal role in forming motor complications. In the
      present study, we tested the possible effect of a CB1 cannabinoid receptor
      agonist on L-DOPA-stimulated abnormal behavioral and signaling responses in vivo.
      Intermittent L-DOPA administration for 3 weeks induced motor fluctuation in a rat
      model of PD induced by intrastriatal infusion of dopamine-depleting neurotoxin 6
      hydroxydopamine (6-OHDA). A single injection of a CB1 cannabinoid receptor
      agonist WIN-55,212-2 had no effect on L-DOPA-induced motor fluctuation. However,
      chronic injections of WIN-55,212-2 significantly attenuated abnormal behavioral
      responses to L-DOPA in 6-OHDA-lesioned rats. Similarly, chronic injections of WIN
      55,212-2 influence the L-DOPA-induced alteration of DARPP-32 and ERK1/2
      phosphorylation status in striatal neurons. These data provide evidence for the
      active involvement of CB1 cannabinoid receptors in the regulation of L-DOPA
      action during PD therapy. 

PMID- 25395835
TI  - Clinical utility of apixaban in the prevention and treatment of venous
      thromboembolism: current evidence.
AB  - Anticoagulation with heparin and vitamin K antagonist has been the mainstay of
      prevention and treatment of venous thromboembolism (VTE) for many years. In
      recent years, novel oral anticoagulants such as dabigatran etexilate (a direct
      thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (a direct factor Xa
      inhibitor) have emerged for the prevention and treatment of VTE. Novel oral
      anticoagulants have been shown to be noninferior to vitamin K antagonist or
      heparin in the prevention and treatment of VTE. This review specifically examines
      the role of apixaban in the prevention and treatment of VTE based on the
      available literature. The management of apixaban in the perioperative setting is
      also explored because some patients on apixaban may require surgical
      intervention. Finally, we discuss the management of apixaban-induced major
      bleeding complications, the relevance of drug-drug interactions, and patient
      education. 

PMID- 25395836
TI  - Involvement of NF-kappaB and HSP70 signaling pathways in the apoptosis of MDA-MB
      231 cells induced by a prenylated xanthone compound, alpha-mangostin, from
      Cratoxylum arborescens.
AB  - BACKGROUND: Cratoxylum arborescens has been used traditionally in Malaysia for
      the treatment of various ailments. METHODS: alpha-Mangostin (AM) was isolated
      from C. arborescens and its cell death mechanism was investigated. AM-induced
      cytotoxicity was observed with the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Acridine orange/propidium iodide
      staining and annexin V were used to detect cells in early phases of apoptosis.
      High-content screening was used to observe the nuclear condensation, cell
      permeability, mitochondrial membrane potential, and cytochrome c release. The
      role of caspases-3/7, -8, and -9, reactive oxygen species, Bcl-2 and Bax
      expression, and cell cycle arrest were also investigated. To determine the role
      of the central apoptosis-related proteins, a protein array followed by immunoblot
      analysis was conducted. Moreover, the involvement of nuclear factor-kappa B (NF
      kappaB) was also analyzed. RESULTS: Apoptosis was confirmed by the apoptotic
      cells stained with annexin V and increase in chromatin condensation in nucleus.
      Treatment of cells with AM promoted cell death-transducing signals that reduced
      MMP by downregulation of Bcl-2 and upregulation of Bax, triggering cytochrome c
      release from the mitochondria to the cytosol. The released cytochrome c triggered
      the activation of caspase-9 followed by the executioner caspase-3/7 and then
      cleaved the PARP protein. Increase of caspase-8 showed the involvement of
      extrinsic pathway. AM treatment significantly arrested the cells at the S phase
      (P<0.05) concomitant with an increase in reactive oxygen species. The protein
      array and Western blotting demonstrated the expression of HSP70. Moreover, AM
      significantly blocked the induced translocation of NF-kappaB from cytoplasm to
      nucleus. CONCLUSION: Together, the results demonstrate that the AM isolated from
      C. arborescens inhibited the proliferation of MDA-MB-231 cells, leading to cell
      cycle arrest and programmed cell death, which was suggested to occur through both
      the extrinsic and intrinsic apoptosis pathways with involvement of the NF-kappaB
      and HSP70 signaling pathways.

PMID- 25395838
TI  - The role of the public in developing interventions: a reflection and critique of
      a cancer clinical trials unit's model.
AB  - The importance of involving lay representatives in research is well-recognized
      but is not consistently meaningfully practiced or reported. Although the positive
      outcomes of lay representative involvement can include more relevant research
      questions and outcomes, challenges are also apparent, including tokenistic
      involvement by research teams. A Cancer Research UK-funded and National Cancer
      Research Institute-registered cancer clinical trials unit in the United Kingdom
      established a program of work to promote genuine and consistent involvement of
      lay representatives (or "research partners") as part of the research team.
      Furthermore, a volunteer was employed to recruit and coordinate the research
      partners in partnership with a national agency for public involvement in health
      and social care research in Wales. This article reports on the development of
      this project and how it will be formally evaluated. Recommendations for involving
      lay representatives are also posed. 

PMID- 25395837
TI  - Caval filters in intensive care: a retrospective study.
AB  - AIM: To evaluate the effectiveness of a caval vein filter (CVF) peri-implant
      monitoring protocol in order to reduce pulmonary embolism (PE) mortality and CVF
      related morbidity. BACKGROUND: The reduction in mortality from PE associated with
      the use of CVF is affected by the risk of increase in morbidity. Therefore, CVF
      implant is a challenging prophylactic or therapeutic option. Nowadays, we have
      many different devices whose rational use, by applying a strict peri-implant
      monitoring protocol, could be safe and effective. MATERIALS AND METHODS: We
      retrospectively studied 62 patients of a general Intensive Care Unit (ICU)
      scheduled for definitive, temporary, or optional bedside CVF implant. A peri
      implant monitoring protocol including a phlebocavography, an echo-Doppler
      examination, and coagulation tests was adopted. RESULTS: In our study, no
      thromboembolic recurrence was registered. We implanted 48 retrievable and only 20
      definitive CVFs. Endothelial adhesion (18%), residual clot (5%), cranial or
      caudal migration (6%), microbial colonization of the filter in the absence of
      clinical signs of infection (1%), caval thrombosis (1%), and pneumothorax (1%)
      were reported. Deep-vein thrombosis (DVT) was reported (8%) as early
      complication. All patients with DVT had a temporary or optional filter implanted.
      However, in our cohort, definitive CVFs were reserved only to 32% of patients and
      they were not associated with DVT as complication. CONCLUSION: CVF significantly
      reduces iatrogenic PE without affecting mortality. Generally, ICU patients have a
      transitory thromboembolic risk, and so the temporary CVF has been proved to be a
      first-line option to our cohort. A careful monitoring may contribute to a
      satisfactory outcome in order to promote CVF implant as a safe prophylaxis
      option.

PMID- 25395839
TI  - Cost utility analysis of immunosuppressive regimens in adult renal transplant
      recipients in England and Wales.
AB  - BACKGROUND: End-stage renal disease is the irreversible final stage of chronic
      kidney disease and is fatal when not managed by either transplantation or
      dialysis. Transplantation is generally preferred over dialysis. However, to
      prevent graft rejection or loss, lifelong immunosuppression is required.
      Tacrolimus is currently the cornerstone of post-transplantation
      immunosuppression. The study aim was to carry out an economic evaluation of
      immunosuppression, including more recent agents such as a once-daily prolonged
      release formulation of tacrolimus (AdvagrafTM) and belatacept, relative to a
      twice-daily immediate-release formulation of tacrolimus (PrografTM). METHODS: A
      MODEL WAS CONSTRUCTED COMPRISING SIX STATES: onset of biopsy-confirmed acute
      rejection, functioning graft with or without a biopsy-confirmed acute rejection,
      non-functioning graft (dialysis), re-transplantation, and death. Data on clinical
      effectiveness were derived from a systematic literature review and the model
      captured the effects of patient adherence to immunosuppressant therapy on graft
      survival using relative risk of graft survival and published data on adherence in
      patients using Advagraf and Prograf. In the base case, the time horizon was 25
      years and one-way and probabilistic sensitivity analyses were conducted. RESULTS:
      The analysis demonstrated that Prograf was cost-effective when compared with
      cyclosporin and belatacept and was more effective than sirolimus, but would not
      be considered cost-effective against sirolimus. The modeled improvement in the
      adherence profile of patients using Advagraf relative to Prograf resulted in both
      improved clinical outcomes and reduced costs. CONCLUSION: Prograf was more
      clinically effective than cyclosporin, belatacept, and sirolimus, supporting its
      current positioning as the mainstay of immunosuppressive therapy in renal
      transplant recipients. Based on improved patient adherence with Advagraf, the
      model projected that Advagraf would be both more effective and less costly than
      Prograf. Replacing Prograf with Advagraf as the standard of care for post
      transplant immunosuppression could likely result in both cost savings and
      improved clinical outcomes.

PMID- 25395840
TI  - To what extent is treatment adherence of psychiatric patients influenced by their
      participation in shared decision making?
AB  - RATIONALE: Nonadherence to prescribed medications is a significant barrier to the
      successful treatment of psychiatric disorders in clinical practice. It has been
      argued that patient participation in shared decision making improves adherence to
      treatment plans. PURPOSE: To assess to what extent treatment adherence of
      psychiatric patients is influenced by the concordance between their preferred
      participation and their actual participation in decision making. MATERIALS AND
      METHODS: A total of 967 consecutive psychiatric outpatients completed the Control
      Preference Scale twice consecutively before consultation, one for their
      preferences of participation, and the other for the style they had usually
      experienced until then, and the eight-item self-report Morisky Medication
      Adherence Scale 8. RESULTS: Most psychiatric outpatients preferred a
      collaborative role in decision making. Congruence was achieved in only 50% of the
      patients, with most mismatch cases preferring more involvement than had been
      experienced. Self-reported adherence was significantly higher in those patients
      in whom there was concordance between their preferences and their experiences of
      participation in decision making, regardless of the type of participation
      preferred. CONCLUSION: Congruence between patients' preferences and actual
      experiences for level of participation in shared decision making is relevant for
      their adherence to treatment.

PMID- 25395841
TI  - Sustainable effects of a low-threshold physical activity intervention on health
      related quality of life in residential aged care.
AB  - BACKGROUND: Mobility is a main issue for health-related quality of life in old
      age. There is evidence for effects of physical activity (PA) interventions on
      several dimensions of health for the aged and also, some specific evidence for
      vulnerable populations, like residents of residential aged care. Research on low
      threshold PA interventions for users of residential aged care and documentation
      of their sustainability are scarce. "Low threshold" implies moderate demands on
      the qualification of trainers and low frequency of conduct, implying low demands
      on the health status and discipline of users. Yet the investigation of low
      threshold interventions in residential aged care seems important as they might
      foster participation of users and implementation in everyday routines of provider
      organizations. An initial study (October 2011 to June 2012) had found
      intervention effects on health-related quality of life. The objective of this
      study was to examine sustainability of the effects of a low-threshold PA
      intervention on health-related quality of life in residential aged care. METHODS:
      Data collection took place in three residential aged care homes in Vienna,
      Austria. At 1-year follow-up (June 2013), participants from the intervention
      group were interviewed using a standardized questionnaire. Using general mixed
      linear models and Friedman tests followed by paired t- and Wilcoxon signed-rank
      tests, we compared outcome measures at follow-up with measures obtained at
      baseline and at the end of the intervention. RESULTS: At the 1-year follow-up
      assessment, participants' (mean age 84.7 years; 89.7% female) subjective health
      status was still significantly increased, equaling a small sustainable
      intervention effect (Cohen's d=0.38, P=0.02). In comparison with baseline, a
      significant decline of reported pain/discomfort (P=0.047) was found. Regarding
      the subdimensions of health-related quality of life, favorable trends could be
      observed. CONCLUSION: The study indicates that effects of a low-threshold PA
      intervention on health-related quality of life in residential aged care can be
      sustainable. Addressing hindering factors like poor health status and
      implementing proactive support and individualization of the program to enable PA
      for residents might foster sustainability of effects.

PMID- 25395842
TI  - Clinical effectiveness of grip strength in predicting ambulation of elderly
      inpatients.
AB  - BACKGROUND: Assessing the clinical effectiveness of measuring grip strength as a
      prognostic tool in recovering ambulation in bed-confined frail elderly patients.
      METHODS: A prospective study was carried out with 50 elderly inpatients (mean
      age: 81.6 years old). Manual muscle test was used for checking strength of hip
      flexor muscles, hip abductor muscles and knee extensor muscles. Grip strength was
      assessed by hydraulic dynamometer. Walking ability was assessed by functional
      ambulation categories and Functional Classification of Sagunto Hospital
      Ambulation. Existence of cognitive impairment (Short Portable Mental Status of
      Pfeiffer) and comorbidity (abbreviated Charlson index) were considered to be
      confounding variables. STATISTICAL ANALYSIS: Simple comparisons and mixed models
      of multiple ordinal regression. RESULTS: The sample presented generalized
      weakness in scapular (mean 4.22) and pelvic (mean 3.82) muscle. Mean hand grip
      values were similar: 11.98 kg right hand; 11.70 kg left hand. The patients had
      lost walking ability. After treatment, there was a statistically significant for
      scapular waist strength (P=0.001), pelvic waist strength (P=0.005) and walking
      ability (P=0.001). A statistically significant relationship in the regression
      analysis was found between the grip (right and left hands) and walking ability
      post-treatment (P=0.009; odds ratio 1.14 and P=0.0014 odds ratio 1.113 for each
      walking scale). The confounding variables showed no statistical significance in
      the results. CONCLUSION: Grip strength is associated with walking ability in
      hospitalized frail elderly. Grip strength assessment by hydraulic dynamometry is
      useful in patients with poor collaboration. Walking ability training in frail
      elderly inpatients is useful.

PMID- 25395843
TI  - Systematic review of raloxifene in postmenopausal Japanese women with
      osteoporosis or low bone mass (osteopenia).
AB  - PURPOSE: To systematically review the literature describing the efficacy,
      effectiveness, and safety of raloxifene for postmenopausal Japanese women with
      osteoporosis or low bone mass (osteopenia). MATERIALS AND METHODS: Medline via
      PubMed and Embase was systematically searched using prespecified terms. Retrieved
      publications were screened and included if they described randomized controlled
      trials or observational studies of postmenopausal Japanese women with
      osteoporosis or osteopenia treated with raloxifene and reported one or more
      outcome measures (change in bone mineral density [BMD]; fracture incidence;
      change in bone-turnover markers, hip structural geometry, or blood-lipid profile;
      occurrence of adverse events; and change in quality of life or pain). Excluded
      publications were case studies, editorials, letters to the editor, narrative
      reviews, or publications from non-peer-reviewed journals; multidrug,
      multicountry, or multidisease studies with no drug-, country-, or disease-level
      analysis; or studies of participants on dialysis. RESULTS: Of the 292
      publications retrieved, 15 publications (seven randomized controlled trials,
      eight observational studies) were included for review. Overall findings were
      statistically significant increases in BMD of the lumbar spine (nine
      publications), but not the hip region (eight publications), a low incidence of
      vertebral fracture (three publications), decreases in markers of bone turnover
      (eleven publications), improved hip structural geometry (two publications),
      improved blood-lipid profiles (five publications), a low incidence of hot
      flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and
      improved quality of life and pain relief (one publication). CONCLUSION: Findings
      support raloxifene for reducing vertebral fracture risk by improving BMD and
      reducing bone turnover in postmenopausal Japanese women with osteoporosis or
      osteopenia. Careful consideration of fracture risk and the risk-benefit profile
      of antiosteoporosis medications is required when managing patients with
      osteoporosis.

PMID- 25395844
TI  - Twelve weeks of BodyBalance(r) training improved balance and functional task
      performance in middle-aged and older adults.
AB  - PURPOSE: The purpose of the study was to evaluate the effect of BodyBalance((r))
      training on balance, functional task performance, fear of falling, and health
      related quality of life in adults aged over 55 years. PARTICIPANTS AND METHODS: A
      total of 28 healthy, active adults aged 66+/-5 years completed the randomized
      controlled trial. Balance, functional task performance, fear of falling, and self
      reported quality of life were assessed at baseline and after 12 weeks.
      Participants either undertook two sessions of BodyBalance per week for 12 weeks
      (n=15) or continued with their normal activities (n=13). RESULTS: Significant
      group-by-time interactions were found for the timed up and go (P=0.038), 30
      second chair stand (P=0.037), and mediolateral center-of-pressure range in narrow
      stance with eyes closed (P=0.017). There were no significant effects on fear of
      falling or self-reported quality of life. CONCLUSION: Twelve weeks of BodyBalance
      training is effective at improving certain balance and functional based tasks in
      healthy older adults.

PMID- 25395845
TI  - Application of a new parameter in the 6-minute walk test for manifold analysis of
      exercise capacity in patients with COPD.
AB  - BACKGROUND: New parameters in the 6-minute walk test (6 MWT) are required for
      comprehensive analysis of exercise capacity in patients with chronic obstructive
      pulmonary disease (COPD). The aim of the present study was to apply a novel
      index, the desaturation distance ratio (DDR), to clinical research on COPD as an
      estimate of exercise capacity and to examine whether DDR is a potential parameter
      for manifold analysis of exercise capacity in patients with COPD. METHODS: A
      total of 41 patients with COPD (median age [interquartile range] =75 [68-79]
      years; and body mass index [BMI] =22.3 [19.4-23.8] kg/m(2)) participated in the
      study. The 6 MWT was performed along with anthropometric measurements and a
      pulmonary function test. The "desaturation area" was measured as the total area
      above the curve created using peripheral oxygen saturation (SpO2) values observed
      at each minute during the 6 MWT. Then the DDR was calculated as the ratio of the
      desaturation area to the 6-minute walk distance (6 MWD). RESULTS: The 6 MWD was
      370 (328-445) m, and the decline in SpO2 values (DeltaSpO2) was -5.0% (-8.0% to 
      1.5%). The DDR correlated modestly with baseline pulmonary function in patients
      with COPD (forced expiratory volume in 1 second [% of predicted value]: r=-0.658,
      P<0.001; and diffusing capacity of the lung for carbon monoxide [DL(CO)]: r=
      0.470, P=0.002), comparable with the findings of the 6 MWD. The DDR correlated
      well with DeltaSpO2 (r=-0.656, P<0.001) and with the increase in subjective sense
      of dyspnea during the 6 MWT, as assessed by Borg scale scores (DeltaBorg)
      (r=0.486, P=0.001), in contrast with the 6 MWD, which was not significantly
      correlated with DeltaSpO2 and DeltaBorg scale scores. CONCLUSION: The DDR is more
      informative for manifold analysis of exercise capacity associated with oxygen
      desaturation and subsequent sense of dyspnea by exercise in patients with COPD.

PMID- 25395846
TI  - Preparation and evaluation of cyclosporin A-containing proliposomes: a comparison
      of the supercritical antisolvent process with the conventional film method.
AB  - OBJECTIVES: The objectives of this study were to prepare cyclosporin A (CsA)
      containing proliposomes using the supercritical antisolvent (SAS) process and the
      conventional thin film method for the comparative study of proliposomal
      formulations and to evaluate the physicochemical properties of these
      proliposomes. METHODS: CsA-containing proliposomes were prepared by the SAS
      process and the conventional film method, composed of natural and synthetic
      phospholipids. We investigated particle size, polydispersity index, and zeta
      potential of CsA-containing proliposomes. In addition, both production yield and
      entrapment efficiency of CsA in different proliposomes were analyzed.
      Physicochemical properties of CsA-containing proliposomes were also evaluated,
      using differential scanning calorimetry and X-ray diffraction. The morphology and
      size of CsA-containing proliposomes were confirmed, using scanning electron
      microscopy. We checked the in vitro release of CsA from CsA-containing
      proliposomes prepared by different preparation methods, comparing them with
      Restasis((r)) as a positive control and the stability of SAS-mediated
      proliposomes was also studied. RESULTS: CsA-containing proliposomes formed by the
      SAS process had a relatively smaller particle size, with a narrow size
      distribution and spherical particles compared with those of conventionally
      prepared proliposomes. The yield and entrapment efficiency of CsA in all
      proliposomes varied from 85% to 92% and from 86% to 89%, respectively.
      Differential scanning calorimetry and X-ray diffraction studies revealed that the
      anhydrous lactose powder used in this formulation retained its crystalline form
      and that CsA was present in an amorphous form. Proliposome powders were rapidly
      converted to liposomes on contact with water. The in vitro release study of
      proliposomal formulations demonstrated a similar pattern to Restasis((r)). The
      SAS-mediated CsA-containing proliposomes were stable on storage, with no
      significant changes in particle size, polydispersity index, and entrapment
      efficiency. CONCLUSION: These results show promising features of CsA-containing
      proliposomal formulations, using the SAS process for the large-scale industrial
      application.

PMID- 25395847
TI  - A histological evaluation and in vivo assessment of intratumoral near infrared
      photothermal nanotherapy-induced tumor regression.
AB  - PURPOSE: Nanoparticle (NP)-enabled near infrared (NIR) photothermal therapy has
      realized limited success in in vivo studies as a potential localized cancer
      therapy. This is primarily due to a lack of successful methods that can prevent
      NP uptake by the reticuloendothelial system, especially the liver and kidney, and
      deliver sufficient quantities of intravenously injected NPs to the tumor site.
      Histological evaluation of photothermal therapy-induced tumor regression is also
      neglected in the current literature. This report demonstrates and histologically
      evaluates the in vivo potential of NIR photothermal therapy by circumventing the
      challenges of intravenous NP delivery and tumor targeting found in other
      photothermal therapy studies. METHODS: Subcutaneous Cal 27 squamous cell
      carcinoma xenografts received photothermal nanotherapy treatments, radial
      injections of polyethylene glycol (PEG)-ylated gold nanorods and one NIR 785 nm
      laser irradiation for 10 minutes at 9.5 W/cm(2). Tumor response was measured for
      10-15 days, gross changes in tumor size were evaluated, and the remaining tumors
      or scar tissues were excised and histologically analyzed. RESULTS: The single
      treatment of intratumoral nanorod injections followed by a 10 minute NIR laser
      treatment also known as photothermal nanotherapy, resulted in ~100% tumor
      regression in ~90% of treated tumors, which was statistically significant in a
      comparison to the average of all three control groups over time (P<0.01).
      CONCLUSION: Photothermal nanotherapy, or intratumoral nanorod injections followed
      by NIR laser irradiation of tumors and tumor margins, demonstrate the potential
      of NIR photothermal therapy as a viable localized treatment approach for primary
      and early stage tumors, and prevents NP uptake by the reticuloendothelial system.

PMID- 25395848
TI  - Stable cerasomes for simultaneous drug delivery and magnetic resonance imaging.
AB  - Magnetic liposomes have been frequently used as nanocarriers for targeted drug
      delivery and magnetic resonance imaging in recent years. Despite great
      potentials, their morphological/structural instability in the physiological
      environment still remains an intractable challenge for clinical applications. In
      this study, stable hybrid liposomal cerasomes (ie, liposomes partially coated
      with silica) which can co-encapsulate Fe3O4 nanoparticles and the anticancer drug
      paclitaxel were developed using thin film hydration method. Compared with the
      drug loaded liposomes, the paclitaxel-loaded magnetic cerasomes (PLMCs) exhibited
      much higher storage stability and better sustained release behavior. Cellular
      uptake study showed that the utilization of an external magnetic field
      significantly facilitated the internalization of PLMCs into cancer cells,
      resulting in potentiated drug efficacy of killing tumor cells. The T2 relaxivity
      (r2) of our PLMCs was much higher than that of free Fe3O4 nanoparticles,
      suggesting increased sensitivity in T2-weighted imaging. Given its excellent
      biocompatibility also shown in the study, such dual functional PLMC is
      potentially a promising nanosystem for effective cancer diagnosis and therapy.

PMID- 25395849
TI  - Stabilization of collagen nanofibers with L-lysine improves the ability of
      carbodiimide cross-linked amniotic membranes to preserve limbal epithelial
      progenitor cells.
AB  - To overcome the drawbacks associated with limited cross-linking efficiency of
      carbodiimide modified amniotic membrane, this study investigated the use of L
      lysine as an additional amino acid bridge to enhance the stability of a
      nanofibrous tissue matrix for a limbal epithelial cell culture platform. Results
      of ninhydrin assays and zeta potential measurements showed that the amount of
      positively charged amino acid residues incorporated into the tissue collagen
      chains is highly correlated with the L-lysine-pretreated concentration. The cross
      linked structure and hydrophilicity of amniotic membrane scaffolding materials
      affected by the lysine molecular bridging effects were determined. With an
      increase in the L-lysine-pretreated concentration from 1 to 30 mM, the cross
      linking density was significantly increased and water content was markedly
      decreased. The variations in resistance to thermal denaturation and enzymatic
      degradation were in accordance with the number of cross-links per unit mass of
      amniotic membrane, indicating L-lysine-modulated stabilization of collagen
      molecules. It was also noteworthy that the carbodiimide cross-linked tissue
      samples prepared using a relatively high L-lysine-pretreated concentration (ie,
      30 mM) appeared to have decreased light transmittance and biocompatibility,
      probably due to the influence of a large nanofiber size and a high charge
      density. The rise in stemness gene and protein expression levels was dependent on
      improved cross-link formation, suggesting the crucial role of amino acid bridges
      in constructing suitable scaffolds to preserve limbal progenitor cells. It is
      concluded that mild to moderate pretreatment conditions (ie, 3-10 mM L-lysine)
      can provide a useful strategy to assist in the development of carbodiimide cross
      linked amniotic membrane as a stable stem cell niche for corneal epithelial
      tissue engineering.

PMID- 25395850
TI  - Silica nanoparticles induce autophagy and endothelial dysfunction via the
      PI3K/Akt/mTOR signaling pathway.
AB  - Although nanoparticles have a great potential for biomedical applications, there
      is still a lack of a correlative safety evaluation on the cardiovascular system.
      This study is aimed to clarify the biological behavior and influence of silica
      nanoparticles (Nano-SiO2) on endothelial cell function. The results showed that
      the Nano-SiO2 were internalized into endothelial cells in a dose-dependent
      manner. Monodansylcadaverine staining, autophagic ultrastructural observation,
      and LC3-I/LC3-II conversion were employed to verify autophagy activation induced
      by Nano-SiO2, and the whole autophagic process was also observed in endothelial
      cells. In addition, the level of nitric oxide (NO), the activities of NO synthase
      (NOS) and endothelial (e)NOS were significantly decreased in a dose-dependent
      way, while the activity of inducible (i)NOS was markedly increased. The
      expression of C-reactive protein, as well as the production of proinflammatory
      cytokines (tumor necrosis factor alpha, interleukin [IL]-1beta, and IL-6) were
      significantly elevated. Moreover, Nano-SiO2 had an inhibitory effect on the
      phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of
      rapamycin (mTOR) signaling pathway. Our findings demonstrated that Nano-SiO2
      could disturb the NO/NOS system, induce inflammatory response, activate
      autophagy, and eventually lead to endothelial dysfunction via the PI3K/Akt/mTOR
      pathway. This indicates that exposure to Nano-SiO2 is a potential risk factor for
      cardiovascular diseases. 

PMID- 25395851
TI  - Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced
      atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan
      nanoparticles.
AB  - BACKGROUND: Atopic dermatitis is a chronic, noncontiguous, and exudative disorder
      accompanied by perivascular infiltration of immune mediators, including T-helper
      (Type 1 helper/Type 2 helper) cells, mast cells, and immunoglobulin E. The
      current study explores the immunomodulatory and histological effects of
      nanoparticle (NP)-based transcutaneous delivery of hydrocortisone (HC). METHODS:
      In this study, HC, the least potent topical glucocorticoid, was administered
      transcutaneously as chitosan NPs. The pharmacological and immunological effects
      of the NP-based HC delivery on the alleviation of 2,4-dinitrofluorobenzene
      induced atopic dermatitis (AD)-like skin lesions were evaluated using the NC/Nga
      mouse model. RESULTS: In vivo Dino-Lite((r)) microscopic assessment revealed that
      the NP-based formulation displayed a remarkable ability to reduce the severity of
      the pathological features of AD (dermatitis index, 3.0). The AD suppressive
      activity of the NP-based topical formulation was expected owing to the
      interruption of a series of immunopathological events, including the production
      of immunoglobulin E, release of histamine, and expression of prostaglandin-E2 and
      vascular endothelial growth factor-alpha in the sera and skin of the tested
      animals. Analysis of the cytokine expression in AD-like skin lesions further
      revealed that the NP-based formulation inhibited the pathological expression of
      interleukin (IL)-4, IL-5, IL-6, IL-13, IL-12p70, interferon-gamma, and tumor
      necrosis factor-alpha in serum and skin homogenates of NC/Nga mice. Further, our
      histological findings indicated that the NP-based formulation inhibited
      fibroblast infiltration and fragmentation of elastic fibers, further supporting
      the clinical importance of these formulations in maintaining the integrity of
      elastic connective tissues. CONCLUSION: The current investigation suggests that
      NP-mediated transcutaneous delivery of HC could be considered an effective
      therapeutic approach to manage dermatitis.

PMID- 25395852
TI  - Upconversion nanoparticles conjugated with curcumin as a photosensitizer to
      inhibit methicillin-resistant Staphylococcus aureus in lung under near infrared
      light.
AB  - Curcumin has phototoxic effects on bacteria under <450 nm irradiation, but it is
      unstable in vivo and cannot exert effects on deep tissues. Near infrared light
      (NIR) is harmless to the body and has stronger penetration than visible light. In
      order to improve the effects of curcumin, upconversion nanoparticles conjugated
      with curcumin (UCNPs-curcumin) are designed to upconvert NIR to the excitation
      wavelength of curcumin. UCNPs-curcumin were synthesized using polyethyleneimine
      to combine curcumin and UCNPs, based on typical composition of lanthanide
      nitrates Re(NO)3 (Y:Yb:Er=78%:20%:2%) linked by ethylenediaminetetraacetic acid
      in sodium fluoride (NaF) matrix, to upconvert NIR to 432 nm light. The product
      was characterized by size distribution, thermogravimetric analysis, differential
      scanning calorimetry, and scanning electron microscopy. Growth inhibition of
      methicillin-resistant Staphylococcus aureus (MRSA) was not only measured in vitro
      but also investigated on MRSA-induced pneumonia in mice. The results showed that
      curcumin was covered by UCNPs to form stable nanoparticles whose average size was
      179.5 nm and zeta potential was -33.7 mV in normal saline. The UCNPs-curcumin
      produced singlet oxygen, which reaches a stable level after 30 minutes of
      irradiation, and took effect on MRSA through bacterial cytoplasm leakage. They
      alleviated MRSA-induced pneumonia and reduced bacterial counts in lungs with 980
      nm irradiation (0.5 W/cm(2)) on chests of mice. It is confirmed that the UCNPs
      curcumin in lungs are activated under NIR irradiation and strengthen their
      antibacterial effects on MRSA. This research provides a new type of NIR
      photosensitizer, which plays an important role in phototoxic effects of curcumin
      in deep tissues under NIR. 

PMID- 25395853
TI  - Spinal cord demyelination combined with hyperhomocysteinemia: a case report.
AB  - Hyperhomocysteinemia (HHcy) has been recognized as an independent risk factor for
      atherosclerotic vascular disease. Here we report a patient who suffered from
      spinal cord demyelination combined with HHcy. The patient was admitted to our
      hospital with a diagnosis of acute myelitis. However, hormone therapy was
      ineffective. Further investigations revealed that he had HHcy and a homozygous
      mutation of the gene encoding methylenetetrahydrofolate reductase (MTHFR)
      c.677C>T, which is a key enzyme involved in homocysteine metabolism. In view of
      these findings, we treated the patient with B vitamins and his symptoms gradually
      improved. Spinal magnetic resonance imaging performed 3 months after onset showed
      near recovery of the lesion. To our knowledge, similar reports are rare. 

PMID- 25395854
TI  - Social cognition and its relationship to functional outcomes in patients with
      sustained acquired brain injury.
AB  - Deficits in social cognition are common after traumatic brain injury (TBI).
      However, little is known about how such deficits affect functional outcomes. The
      purpose of this study was to investigate the relationship between social
      cognition and functional outcomes in patients with TBI. We studied this
      relationship in 20 patients with TBI over the course of 1 year post-injury.
      Patients completed neurocognitive assessments and social cognition tasks. The
      social cognition tasks included an emotion-perception task and three theory of
      mind tasks: the Faux Pas test, Reading the Mind in the Eyes (Eyes) test, and the
      Moving-Shapes paradigm. The Craig Handicap Assessment and Reporting Technique was
      used to assess functional outcomes. Compared with our database of normal
      subjects, patients showed impairments in all social cognition tasks. Multiple
      regression analysis revealed that theory of mind ability as measured by the Eyes
      test was the best predictor of the cognitive aspects of functional outcomes. The
      findings of this pilot study suggest that the degree to which a patient can
      predict what others are thinking is an important measure that can estimate
      functional outcomes over 1 year following TBI. 

PMID- 25395855
TI  - Intracranial malignant lesions correlate with the requirement for a long
      treatment course in postoperative central nervous system infection.
AB  - AIM: Our aim was to study the clinical features of postoperative meningitis after
      neurosurgery and identify the factors affecting the duration of treatment.
      METHODS: This retrospective study assessed 283 patients with postoperative
      bacterial meningitis in the Neurosurgery Department of Beijing Tiantan Hospital,
      Beijing, People's Republic of China, between January and December 2012. Patients'
      clinical data were reviewed, and multivariate logistic regression analysis was
      used to identify the factors associated with a prolonged treatment course.
      RESULTS: The mortality rate was 0.4% in these patients, of whom 12.4% were found
      with pathogens in the cerebrospinal fluid. Among the three most common pathogens
      detected were methicillin-resistant Staphylococcus aureus, Acinetobacter
      baumannii, and Pseudomonas aeruginosa. The mean treatment course was 13.5+/-2.1
      days. Interestingly, the treatment duration for postoperative meningitis was
      significantly longer in patients with intracranial malignant tumors than in those
      with benign lesions. Single-factor analysis showed that male sex (P=0.042) and
      malignant (rather than benign) lesions (P<0.001) were significantly associated
      with prolonged treatment duration. Multivariate analysis further confirmed that
      malignant intracranial lesions represented an independent risk factor for
      prolonged treatment duration (odds ratio: 2.5962; 95% confidence interval: 1.1092
      6.6134). CONCLUSION: The nature of the intracranial lesion is an independent risk
      factor for the duration of treatment in postoperative meningitis after
      neurosurgery.

PMID- 25395856
TI  - Can low brain-derived neurotrophic factor levels be a marker of the presence of
      depression in obese women?
AB  - OBJECTIVE: Depression is a common condition in obese women that can result in
      severe impairment of their physical and social functioning. A deficiency of brain
      derived neurotrophic factor (BDNF) is involved in the mechanism of depression.
      The aim of this study is to investigate whether BDNF levels differ between obese
      female patients and healthy controls and whether BDNF levels alter with affective
      states in depressive obese women. METHODS: The study group included 40 obese, 40
      preobese, and 40 normal weight women. BDNF levels were measured with an enzyme
      linked immunosorbent assay in patient and control groups. For identifying the
      depression and anxiety status, Beck Depression/Anxiety Inventories were used; and
      for the evaluation of cognitive functions, the mini-mental state examination was
      used. RESULTS: BDNF levels were significantly lower in obese patients compared to
      the control group (P<0.01). BDNF levels were significantly lower in obese
      patients with depression compared to the obese patients without depression
      (P<0.05). The Beck Depression Inventory showed a negative correlation with BDNF
      (r=-0.044; P<0.01) and a positive correlation with the Beck Anxiety Inventory
      (r=0.643; P<0.001), vitamin B12 levels (r=0.023; P<0.001), and insulin levels
      (r=0.257; P<0.05) in obese patients. When receiver operating characteristic curve
      analysis was used to analyze the suitability of BDNF to identify depression in
      obese women, the area under the curve for BDNF, 0.756, was found to be
      significant (P=0.025). BDNF levels lower than 70.2 pg/mL were associated with a
      higher prevalence of depressive symptoms. CONCLUSION: The results of our study
      suggest that the decrease in BDNF levels can be used as a marker for depression
      diagnosis in obese patients.

PMID- 25395857
TI  - Meta-analysis of oral contraceptives and rheumatoid arthritis risk in women.
AB  - BACKGROUND AND OBJECTIVES: Epidemiological investigations of the relationship
      between oral contraceptives and rheumatoid arthritis (RA) risk have reported
      controversial results. Therefore, a meta-analysis of case-control or cohort
      studies was performed to evaluate the role of oral contraceptives in relation to
      risk of developing RA. METHODS: Eligible studies were identified from databases
      PubMed and EMBASE by searching and reviewing references. Random effect models
      were utilized to summarize the relative risk (RR) estimates with 95% confidence
      intervals (CIs). RESULTS: A total of 12 case-control studies and five cohort
      studies were eligible for our analysis. No statistically significant association
      was observed between oral contraceptives and RA risk (RR=0.88, 95% CI=0.75-1.03).
      In the subgroup of geographic area, a decreased risk of borderline significance
      was observed for oral contraceptive users in European studies (RR=0.79, 95%
      CI=0.62-1.01), but this association did not emerge in the North American studies
      group (RR=0.99, 95% CI=0.81-1.21). No evidence for publication bias was detected
      (P for Egger's test =0.231). CONCLUSION: Our results of meta-analysis do not
      support the hypothesis of a protective effect of oral contraceptives on the risk
      for RA in women.

PMID- 25395858
TI  - Congenital anomaly of the inferior vena cava and factor V Leiden mutation
      predisposing to deep vein thrombosis.
AB  - A previously healthy 21-year-old man presented with back pain, bilateral
      extremity pain, and right lower extremity weakness, paresthesias, and swelling.
      Sonographic examination revealed diffuse deep vein thrombosis (DVT) in the
      femoral and popliteal venous system. CT imaging revealed hypoplasia of the
      hepatic inferior vena cava (IVC) segment with formation of multiple varices and
      collateral veins around the kidneys. Hematologic workup also discovered a factor
      V Leiden mutation, further predisposing the patient to DVT. The rare, often
      overlooked occurrence of attenuated IVC, especially in the setting of
      hypercoagulable state, can predispose patients to significant thrombosis. 

PMID- 25395860
TI  - Implementation of a collaborative care model for the treatment of depression and
      anxiety in a community health center: results from a qualitative case study.
AB  - BACKGROUND: The collaborative care model is a systematic approach to the
      treatment of depression and anxiety in primary care settings that involves the
      integration of care managers and consultant psychiatrists, with primary care
      physician oversight, to more proactively manage mental disorders as chronic
      diseases, rather than treating acute symptoms. While collaborative care has been
      shown to be more effective than usual primary care in improving depression
      outcomes in a number of studies, less is known about the factors that support the
      translation of this evidence-based intervention to real-world program
      implementation. The purpose of this case study was to examine the implementation
      of a collaborative care model in a community based primary care clinic that
      primarily serves a low-income, uninsured Latino population, in order to better
      understand the interdisciplinary relationships and the specific elements that
      might facilitate broader implementation. METHODS: An embedded single-case study
      design was chosen in order to thoroughly examine the components of one of several
      programs within a single organization. The main unit of analysis was semi
      structured interviews that were conducted with seven clinical and administrative
      staff members. A grounded theory approach was used to analyze the interviews.
      Line-by-line initial coding resulted in over 150 initial codes, which were
      clustered together to rebuild the data into preliminary categories and then
      divided into four final categories, or main themes. RESULTS: FOUR UNIQUE THEMES
      ABOUT HOW THE IMPLEMENTATION OF A COLLABORATIVE CARE MODEL WORKED IN THIS SETTING
      EMERGED FROM THE INTERVIEWS: organizational change, communication, processes and
      outcomes of the program, and barriers to implementation. Each main theme had a
      number of subthemes that provided a detailed description of the implementation
      process and how it was unique in this setting. CONCLUSION: The results indicated
      that adequate training and preparation, acceptance and support from key
      personnel, communication barriers, tools for systematic follow-up and
      measurement, and organizational stability can significantly impact successful
      implementation. Further research is necessary to understand how organizational
      challenges may affect outcomes for patients.

PMID- 25395859
TI  - Improving medication adherence in hypercholesterolemia: challenges and solutions.
AB  - Medication nonadherence is a prevalent public health issue that contributes to
      significant medical costs and detrimental health outcomes. This is especially
      true in patients with hypercholesterolemia, a condition affecting millions of
      American adults and one that is associated with increased risk for coronary and
      cerebrovascular events. Considering the magnitude of outcomes related to this
      disease, the medical community has placed significant emphasis on addressing the
      treatment for high cholesterol, and progress has been made in recent years.
      However, poor adherence to therapy continues to plague health outcomes and more
      must be understood and done to address suboptimal medication taking. Here we
      provide an overview of the reasons for poor medication adherence in patients with
      hypercholesterolemia and describe recent efforts to curb nonadherence. Suggested
      approaches for improving medication taking in patients with high cholesterol are
      also provided to guide practitioners, patients, and payers. 

PMID- 25395861
TI  - Five-year tracking of Plasmodium falciparum allele frequencies in a holoendemic
      area with indistinct seasonal transitions.
AB  - BACKGROUND: The renewed malaria eradication efforts require an understanding of
      the seasonal patterns of frequency of polymorphic variants in order to focus
      limited funds productively. Although cross-sectional studies in holoendemic areas
      spanning a single year could be useful in describing parasite genotype status at
      a given point, such information is inadequate in describing temporal trends in
      genotype polymorphisms. For Plasmodium falciparum isolates from Kisumu District
      Hospital, Plasmodium falciparum chloroquine-resistance transporter gene (Pfcrt
      K76T) and P. falciparum multidrug resistance gene 1 (PfMDR1-N86Y), were analyzed
      for polymorphisms and parasitemia changes in the 53 months from March 2008 to
      August 2012. Observations were compared with prevailing climatic factors,
      including humidity, rainfall, and temperature. METHODS: Parasitemia (the
      percentage of infected red blood cells per total red blood cells) was established
      by microscopy for P. falciparum malaria-positive samples. P. falciparum DNA was
      extracted from whole blood using a Qiagen DNA Blood Mini Kit. Single nucleotide
      polymorphism identification at positions Pfcrt-K76T and PfMDR1-N86Y was performed
      using real-time polymerase chain reaction and/or sequencing. Data on climatic
      variables were obtained from http://www.tutiempo.net/en/. RESULTS: A total of 895
      field isolates from 2008 (n=169), 2009 (n=161), 2010 (n=216), 2011 (n=223), and
      2012 (n=126) showed large variations in monthly frequency of PfMDR1-N86Y and
      Pfcrt-K76T as the mutant genotypes decreased from 68.4%+/-15% and 38.1%+/-13% to
      29.8%+/-18% and 13.3%+/-9%, respectively. The mean percentage of parasitemia was
      2.61%+/-1.01% (coefficient of variation 115.86%; n=895). There was no correlation
      between genotype or parasitemia and climatic factors. CONCLUSION: This study
      shows variability in the frequency of Pfcrt-K76T and PfMDR1-N86Y polymorphisms
      during the study period, bringing into focus the role of cross-sectional studies
      in describing temporal genotype trends. The lack of correlation between genotypes
      and climatic changes, especially precipitation, emphasizes the cost of investment
      in genotype change.

PMID- 25395863
TI  - Clinical outcome of advanced and metastatic renal cell carcinoma treated with
      targeted therapy: is there a difference between young and old patients?
AB  - BACKGROUND: To assess whether the clinical outcome of advanced and metastatic
      renal cell carcinoma (mRCC) treated with targeted therapy differs between young
      and old patients. PATIENTS AND METHODS: A total of 327 patients with advanced
      renal cell carcinoma and mRCC who received targeted therapy in two Chinese
      clinical centers were analyzed retrospectively. The patients were stratified into
      three groups: young (aged <45 years), middle-aged (aged 45-64 years), and old
      (aged >=65 years). Overall survival (OS) and progression-free survival (PFS)
      curves were drawn using the Kaplan-Meier method, and Cox's proportional hazard
      regression model was used to compare OS and PFS within age groups. RESULTS: There
      were no significant differences among young, middle-aged, and old groups in terms
      of OS (P=0.087), whereas PFS in the old group was significantly better than in
      the young and middle-aged groups (P=0.043). Both OS and PFS in the younger groups
      (aged <65 years) were significantly worse than in the old group (age >=65 years;
      median OS, 28.1 vs 28.7 months [P=0.029]; median PFS, 11.4 vs 14 months
      [P=0.015]). No difference in OS or PFS was found between the young and middle
      aged groups. After adjusting for sex, body mass index, smoking status,
      hypertension, diabetes mellitus, Eastern Cooperative Oncology Group score,
      history of cytokines, and Fuhrman grade, old age was an independent favorable
      prognostic factor for OS and PFS compared with younger age (<65 years) (OS,
      hazard ratio, 0.552 [95% confidence interval, 0.329-0.828; P=0.006]; PFS, hazard
      ratio, 0.584 [95% confidence interval, 0.401-0.850; P=0.005]). CONCLUSION:
      Younger patients with advanced renal cell carcinoma and mRCC receiving targeted
      therapy have a poorer prognosis compared with old patients. These results remain
      to be examined in prospective cohorts.

PMID- 25395862
TI  - Antisense therapeutics in oncology: current status.
AB  - There is increasing progress in translational oncology and tremendous
      breakthroughs have been made as evidenced by preclinical and clinical trials.
      Data obtained from high-throughput technologies are deepening our understanding
      about the molecular and gene network in cancer cells and rapidly emerging in
      vitro and in vivo evidence is highlighting the role of antisense agents as
      specific inhibitors of the expression of target genes, thus modulating the
      response of cancer cells to different therapeutic strategies. Much information is
      continuously being added into various facets of molecular oncology and it is now
      understood that overexpression of antiapoptotic proteins, oncogenes, oncogenic
      microRNAs (miRNA), and fusion proteins make cancer cells difficult to target.
      Delivery of antisense oligonucleotides has remained a challenge and technological
      developments have helped in overcoming hurdles by improving the ability to
      penetrate cells, effective and targeted binding to gene sequences, and
      downregulation of target gene function. Different delivery systems, including
      stable nucleic acid lipid particles, have shown potential in enhancing the
      delivery of cargo to the target site. In this review, we attempt to summarize the
      current progress in the development of antisense therapeutics and their potential
      in medical research. We partition this multicomponent review into introductory
      aspects about recent breakthroughs in antisense therapeutics. We also discuss how
      antisense therapeutics have shown potential in resensitizing resistant cancer
      cells to apoptosis by targeted inhibition of antiapoptotic proteins, oncogenic
      miRNAs, and BCR-ABL. 

PMID- 25395864
TI  - The effect of laughter therapy on radiation dermatitis in patients with breast
      cancer: a single-blind prospective pilot study.
AB  - BACKGROUND: There have not yet been any published studies on the effects of
      laughter therapy on radiation-induced dermatitis in breast cancer patients
      treated with radiotherapy (RT). We assessed the effectiveness of laughter therapy
      in preventing radiation dermatitis in patients with breast cancer. METHODS:
      Thirty-seven patients were prospectively enrolled in this study. Eighteen
      patients were assigned to the experimental group and the other 19 patients were
      assigned to the control group. The patients who were assigned to the experimental
      group received laughter therapy during RT. Laughter therapy was started at the
      onset of RT and was provided twice a week until completion of RT. The patients
      who were assigned to the control group only received RT without laughter therapy.
      The grade of radiation dermatitis was scored by a radiation oncologist who was
      blinded to subject assignment. The patients' evaluation of pain within the RT
      field was also assessed. RESULTS: In the experimental group, radiation dermatitis
      of grade 3, 2, and 1 developed in five (33.3%), five (33.3%), and five patients
      (33.3%), respectively. In comparison, in the control group, radiation dermatitis
      of grade 3, 2, 1, and 0 developed in seven (36.8%), nine (47.4%), two (10.5%),
      and one patient (5.3%), respectively. The experimental group exhibited a lower
      incidence of grade 2 or worse radiation dermatitis than the control group (33.3%
      versus 47.4%). The mean maximal pain scores in the experimental and control group
      were 2.53 and 3.95, respectively. The experimental group complained of less
      severe pain than the control group during RT. However, these differences were not
      statistically significant. CONCLUSION: The results of this study show that
      laughter therapy can have a beneficial role in preventing radiation dermatitis in
      patients with breast cancer. To confirm the results of our study, well-designed
      randomized studies with large sample sizes are required.

PMID- 25395865
TI  - Middle East respiratory syndrome coronavirus: epidemiology and disease control
      measures.
AB  - The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV)
      infection in 2012 resulted in an increased concern of the spread of the infection
      globally. MERS-CoV infection had previously caused multiple health-care
      associated outbreaks and resulted in transmission of the virus within families.
      Community onset MERS-CoV cases continue to occur. Dromedary camels are currently
      the most likely animal to be linked to human MERS-CoV cases. Serologic tests
      showed significant infection in adult camels compared to juvenile camels. The
      control of MERS-CoV infection relies on prompt identification of cases within
      health care facilities, with institutions applying appropriate infection control
      measures. In addition, determining the exact route of transmission from camels to
      humans would further add to the control measures of MERS-CoV infection. 

PMID- 25395866
TI  - Bacterial bloodstream infections and antimicrobial susceptibility pattern in
      pediatric hematology/oncology patients after anticancer chemotherapy.
AB  - PURPOSE: Bloodstream infections in pediatric hematology and oncology represent a
      major problem worldwide, but this has not been studied in Qatar. In this study,
      we investigated the burden of infection and the resistance pattern in the
      bacterial etiology, in the only tertiary pediatric hematology and oncology center
      in Qatar. METHODS: All pediatric cancer patients (n=185) were evaluated
      retrospectively during the period 2004-2011; a total of 70 (38%) patients were
      diagnosed with bloodstream infections. Bacterial etiology was determined, along
      with their susceptibility patterns. Neutropenia, duration of neutropenia, fever,
      duration of fever, and C-reactive protein (CRP) were evaluated throughout the
      study. RESULTS: A total of 70 patients (38%) were diagnosed with acute leukemias,
      lymphomas, solid tumors, or brain tumors; those patients experienced 111 episodes
      of bacteremia. The most common Gram-positive (n=64 [55%]) isolates were
      Staphylococcus epidermidis (n=26), Staphylococcus hominis (n=9), and
      Staphylococcus haemolyticus (n=7), and the common Gram-negative (n=52 [45%])
      isolates were Klebsiella pneumoniae (n=14), Pseudomonas aeruginosa (n=10), and
      Escherichia coli (n=7). There was a significant association observed between
      fever with positive blood culture and different types of cancer (P=0.035). The
      majority of bacteremia (n=68 [61.3%]) occurred in nonneutropenic episodes.
      Elevated values of CRP (>=5 mg/L) were detected in 82 (95.3%) episodes and were
      negatively correlated with absolute neutrophil count (ANC) (r=-0.18; P=0.248)
      among all cases. However, the infection-related fatality rate was 2.2% (n=4),
      with three caused by Gram-negative pathogens. Multidrug resistant organisms were
      implicated in 33 (28.4%) cases and caused three of the mortality cases.
      CONCLUSION: Multidrug resistant organisms cause mortality in pediatric cancer
      patients. Investigation of antimicrobial susceptibility of these organisms may
      guide successful antimicrobial therapy and improve the surveillance and quality
      of pediatric malignancy care.

PMID- 25395867
TI  - Measurement properties of painDETECT by average pain severity.
AB  - BACKGROUND: Since the burden of neuropathic pain (NeP) increases with pain
      severity, it is important to characterize and quantify pain severity when
      identifying NeP patients. This study evaluated whether painDETECT, a screening
      questionnaire to identify patients with NeP, can distinguish pain severity.
      MATERIALS AND METHODS: Subjects (n=614, 55.4% male, 71.8% white, mean age 55.5
      years) with confirmed NeP were identified during office visits to US community
      based physicians. The Brief Pain Inventory - Short Form stratified subjects by
      mild (score 0-3, n=110), moderate (score 4-6, n=297), and severe (score 7-10,
      n=207) average pain. Scores on the nine-item painDETECT (seven pain-symptom
      items, one pain-course item, one pain-irradiation item) range from -1 to 38
      (worst NeP); the seven-item painDETECT scores (only pain symptoms) range from 0
      to 35. The ability of painDETECT to discriminate average pain-severity levels,
      based on the average pain item from the Brief Pain Inventory - Short Form (0-10
      scale), was evaluated using analysis of variance or covariance models to obtain
      unadjusted and adjusted (age, sex, race, ethnicity, time since NeP diagnosis,
      number of comorbidities) mean painDETECT scores. Cumulative distribution
      functions on painDETECT scores by average pain severity were compared (Kolmogorov
      Smirnov test). Cronbach's alpha assessed internal consistency reliability.
      RESULTS: Unadjusted mean scores were 15.2 for mild, 19.8 for moderate, and 24.0
      for severe pain for the nine items, and 14.3, 18.6, and 22.7, respectively, for
      the seven items. Adjusted nine-item mean scores for mild, moderate, and severe
      pain were 17.3, 21.3, and 25.3, respectively; adjusted seven-item mean scores
      were 16.4, 20.1, and 24.0, respectively. All pair-wise comparisons of scores
      between pain-severity groups showed sizable and statistically significant
      differences (P<0.0001). Cumulative distribution functions showed distinct
      separation between severity (P<0.0001). Cronbach's alphas were 0.76 and 0.80 for
      the nine- and seven-item scales, respectively. CONCLUSION: This study provides
      strong psychometric evidence on the validity and reliability of painDETECT for
      distinguishing average pain severity in patients with NeP.

PMID- 25395868
TI  - Fibroblasts and myofibroblasts in wound healing.
AB  - (Myo)fibroblasts are key players for maintaining skin homeostasis and for
      orchestrating physiological tissue repair. (Myo)fibroblasts are embedded in a
      sophisticated extracellular matrix (ECM) that they secrete, and a complex and
      interactive dialogue exists between (myo)fibroblasts and their microenvironment.
      In addition to the secretion of the ECM, (myo)fibroblasts, by secreting matrix
      metalloproteinases and tissue inhibitors of metalloproteinases, are able to
      remodel this ECM. (Myo)fibroblasts and their microenvironment form an evolving
      network during tissue repair, with reciprocal actions leading to cell
      differentiation, proliferation, quiescence, or apoptosis, and actions on growth
      factor bioavailability by binding, sequestration, and activation. In addition,
      the (myo)fibroblast phenotype is regulated by mechanical stresses to which they
      are subjected and thus by mechanical signaling. In pathological situations
      (excessive scarring or fibrosis), or during aging, this dialogue between the
      (myo)fibroblasts and their microenvironment may be altered or disrupted, leading
      to repair defects or to injuries with damaged and/or cosmetic skin alterations
      such as wrinkle development. The intimate dialogue between the (myo)fibroblasts
      and their microenvironment therefore represents a fascinating domain that must be
      better understood in order not only to characterize new therapeutic targets and
      drugs able to prevent or treat pathological developments but also to interfere
      with skin alterations observed during normal aging or premature aging induced by
      a deleterious environment. 

PMID- 25395869
TI  - Reexamination of the relationship between the prevalence of hepatitis C virus and
      parenteral antischistosomal therapy among Egyptians resident in Qatar.
AB  - Egypt has the highest prevalence of recorded hepatitis C virus (HCV) worldwide,
      estimated nationally at 14.7%, which is attributed to extensive iatrogenic
      transmission during the era of parenteral antischistosomal therapy (PAT) mass
      treatment campaigns. The objective of our study was to attempt to highlight to
      what extent HCV transmission is ongoing and discuss the possible risk factors. We
      studied the prevalence of HCV among 7.8% of Egyptians resident in Qatar in
      relation to age, socioeconomic status, and PAT and discuss the possible risk
      factors. HCV testing was conducted in 2,335 participants, and results were
      positive for 13.5%, and 8.5% for those aged below 35 years. The prevalence of HCV
      in the PAT-positive population was 23.7% (123 of 518, 95% confidence interval
      [CI] 20.2%-27.6%) compared with 11.2% in the PAT-negative group. Significantly
      higher HCV prevalence occurred in participants who were older than 50 years (23%,
      95% CI 19.3%-27.1%) compared to those aged 45-50 years (19.3%, 95% CI 15.2%
      23.8%), 35-45 years (11.1%, 95% CI 8.9%-13.7%), and less than 35 years (8.5%, 95%
      CI 6.8%-10.4%) (P<0.0001). Insignificant higher prevalence occurred in the low
      socioeconomic group (14.2%, 95% CI 11.3%-17.4%). Logistic regression analysis
      revealed that increasing age, history of PAT, bilharziasis, and praziquantel were
      common risk factors, but there was no relation with dental care. Host genetic
      predisposition seems to be a plausible underlying factor for susceptibility among
      Egyptians and intense ongoing infection. 

PMID- 25395870
TI  - Current perspectives on intrathecal drug delivery.
AB  - Advances in intrathecal analgesia and intrathecal drug delivery systems have
      allowed for a range of medications to be used in the control of pain and
      spasticity. This technique allows for reduced medication doses that can decrease
      the side effects typically associated with oral or parenteral drug delivery.
      Recent expert panel consensus guidelines have provided care paths in the
      treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data
      for pain relief, adverse effect reduction, and cost-effectiveness with cancer
      pain control are compelling, the evidence is less clear for noncancer pain, other
      than spasticity. Physicians should be aware of mechanical, pharmacological,
      surgical, and patient-specific complications, including possible granuloma
      formation. Newer intrathecal drug delivery systems may allow for better safety
      and quality of life outcomes. 

PMID- 25395871
TI  - Pregnancy-associated breast cancer: optimal treatment options.
AB  - Cancer is diagnosed approximately once per 1,000 pregnancies; most commonly due
      to the reproductive age of the women, these include breast, cervical, melanoma,
      thyroid, and Hodgkin's lymphoma diagnoses. As a single diagnosis, breast cancer
      is the most common cancer diagnosed during pregnancy. Cancer is expected to
      complicate pregnancy more often due to the trend for women to delay child bearing
      to later maternal ages. Delayed first birth is itself a risk factor for breast
      cancer. Termination of pregnancy has not been shown to afford a survival benefit.
      While protecting the interests of mother and unborn fetus, breast cancer can be
      safely diagnosed, staged, and treated during pregnancy with good outcomes for
      both. Some modification of the protocols used for nonpregnant women with
      suspicious palpable breast masses is required. This article reviews the
      challenges for physicians in making the diagnosis of breast cancer during
      pregnancy and upon diagnosis, counseling patients about treatment options. The
      consequences of diagnostic investigations and cancer treatment for the exposed
      fetus are also addressed. 

PMID- 25395872
TI  - Effects of 16-week high-intensity interval training using upper and lower body
      ergometers on aerobic fitness and morphological changes in healthy men: a
      preliminary study.
AB  - It is unclear whether combined leg and arm high-intensity interval training
      (HIIT) improves fitness and morphological characteristics equal to those of leg
      based HIIT programs. The aim of this study was to compare the effects of HIIT
      using leg-cycling (LC) and arm-cranking (AC) ergometers with an HIIT program
      using only LC. Effects on aerobic capacity and skeletal muscle were analyzed.
      Twelve healthy male subjects were assigned into two groups. One performed LC-HIIT
      (n=7) and the other LC- and AC-HIIT (n=5) twice weekly for 16 weeks. The training
      programs consisted of eight to 12 sets of >90% VO2 (the oxygen uptake that can be
      utilized in one minute) peak for 60 seconds with a 60-second active rest period.
      VO2 peak, watt peak, and heart rate were measured during an LC incremental
      exercise test. The cross-sectional area (CSA) of trunk and thigh muscles as well
      as bone-free lean body mass were measured using magnetic resonance imaging and
      dual-energy X-ray absorptiometry. The watt peak increased from baseline in both
      the LC (23%+/-38%; P<0.05) and the LC-AC groups (11%+/-9%; P<0.05). The CSA of
      the quadriceps femoris muscles also increased from baseline in both the LC (11%+/
      4%; P<0.05) and the LC-AC groups (5%+/-5%; P<0.05). In contrast, increases were
      observed in the CSA of musculus psoas major (9%+/-11%) and musculus anterolateral
      abdominal (7%+/-4%) only in the LC-AC group. These results suggest that a
      combined LC- and AC-HIIT program improves aerobic capacity and muscle hypertrophy
      in both leg and trunk muscles. 

PMID- 25395873
TI  - Pyrethroid insecticide exposure in school-aged children living in rice and
      aquacultural farming regions of Thailand.
AB  - BACKGROUND: Pyrethroid insecticides (PYR) are commonly used in rice farms and
      household pest control in Thailand. No investigative study has yet been made
      regarding factors associated with PYR exposure among Thai children. OBJECTIVE:
      This study aimed to compare the levels of PYR exposure between children living in
      rice farms (high-intensity PYR used) and aquacultural areas (low-intensity PYR
      used) during the wet and dry seasons in Thailand, during which different amounts
      of PYR are applied. Environmental conditions and common activities of children
      were used to identify factors associated with PYR exposure. METHODS: A cross
      sectional study was done during the wet and dry seasons, respectively. A total of
      53 participants aged between 6 and 8 years old were recruited from rice farms and
      aquacultural areas. A parental-structured interview was used to gather
      information about PYR use, household environments, and participants' activities.
      First voided morning urine samples were collected for PYR urinary metabolites
      (ie, 3-phenoxybenzoic acid [3-PBA] and cis/trans-3-(2,2-dichlorovinyl)-2,2
      dimethylcyclopropane carboxylic acid [DCCA]) measurements. Hand wipe samples were
      collected during home visits, to measure PYR residues on the hands. RESULTS AND
      DISCUSSION: The concentrations of urinary PYR metabolites were not significantly
      different between participants who lived in rice farming and those who lived in
      aquacultural areas, during both wet and dry seasons. Both participant groups had
      slightly increased urinary PYR metabolites during the wet season compared with
      the dry season. The results from linear regression analysis revealed that some
      environmental conditions and activities or practices may be used to predict
      trends of PYR exposure. Frequency of PYR use in farms (beta=0.004) and households
      (beta=0.07), proximity to rice farms (beta=0.09), playing in rice farms
      (beta=0.11), and oral exposure from objects exposed to PYR (beta=0.08) were
      likely to be related to increased concentrations of PYR metabolites. These
      findings suggest that PYR use in rice farms and households may be significant
      sources of PYR exposure among children living in agricultural areas. However, a
      bigger sample size may be necessary in a subsequent study, to explore the
      association between long-term exposure to pesticide and its health effects on
      children.

PMID- 25395874
TI  - Sleep deprivation impairs recall of social transmission of food preference in
      rats.
AB  - Evidence indicates that sleep plays an important role in learning and memory, and
      disruption of sleep especially seems to interfere with hippocampal memory
      processes. Social transmission of food preference (STFP), a natural test of
      paired associative learning, has been shown to be dependent on the hippocampus.
      While social transmission of food preference is not a novel task, it has not been
      used to examine the role of sleep in memory consolidation. Male Sprague-Dawley
      rats were randomly divided into three groups: cage control; sleep-deprived; and
      device control. Demonstrator rats were given powdered food mixed with a target
      spice. Test rats then interacted with demonstrator rats before being given a two
      choice test of powered food with the target spice or a novel spice. Sleep
      deprived rats were then placed in an automated device that prevented sleep for 24
      hours. After sleep deprivation, animals were given a preference test again to
      determine memory for the target spice at both 24 hours and 72 hours.
      Polysomnography was used to validate the method of sleep deprivation. During
      immediate preference testing, rats demonstrated a clear preference for the food
      containing the target spice. Rats that experienced 24 hours of sleep deprivation
      following the initial testing indicated a significant reduction in the recall of
      the target spice at 24 and 72 hours. The cage control and device animals
      maintained their preference for food containing the target spice. Therefore, the
      loss of sleep interfered with memory consolidation for food preference learned
      via social transmission. 

PMID- 25395875
TI  - Deriving a preference-based utility measure for cancer patients from the European
      Organisation for the Research and Treatment of Cancer's Quality of Life
      Questionnaire C30: a confirmatory versus exploratory approach.
AB  - BACKGROUND: Multi attribute utility instruments (MAUIs) are preference-based
      measures that comprise a health state classification system (HSCS) and a scoring
      algorithm that assigns a utility value to each health state in the HSCS. When
      developing a MAUI from a health-related quality of life (HRQOL) questionnaire,
      first a HSCS must be derived. This typically involves selecting a subset of
      domains and items because HRQOL questionnaires typically have too many items to
      be amendable to the valuation task required to develop the scoring algorithm for
      a MAUI. Currently, exploratory factor analysis (EFA) followed by Rasch analysis
      is recommended for deriving a MAUI from a HRQOL measure. AIM: To determine
      whether confirmatory factor analysis (CFA) is more appropriate and efficient than
      EFA to derive a HSCS from the European Organisation for the Research and
      Treatment of Cancer's core HRQOL questionnaire, Quality of Life Questionnaire
      (QLQ-C30), given its well-established domain structure. METHODS: QLQ-C30 (Version
      3) data were collected from 356 patients receiving palliative radiotherapy for
      recurrent/metastatic cancer (various primary sites). The dimensional structure of
      the QLQ-C30 was tested with EFA and CFA, the latter informed by the established
      QLQ-C30 structure and views of both patients and clinicians on which are the most
      relevant items. Dimensions determined by EFA or CFA were then subjected to Rasch
      analysis. RESULTS: CFA results generally supported the proposed QLQ-C30 structure
      (comparative fit index =0.99, Tucker-Lewis index =0.99, root mean square error of
      approximation =0.04). EFA revealed fewer factors and some items cross-loaded on
      multiple factors. Further assessment of dimensionality with Rasch analysis
      allowed better alignment of the EFA dimensions with those detected by CFA.
      CONCLUSION: CFA was more appropriate and efficient than EFA in producing
      clinically interpretable results for the HSCS for a proposed new cancer-specific
      MAUI. Our findings suggest that CFA should be recommended generally when deriving
      a preference-based measure from a HRQOL measure that has an established domain
      structure.

PMID- 25395876
TI  - Measurement error in air pollution epidemiology: Guidance for uncertain times.

PMID- 25395877
TI  - Zeolite Y Adsorbents with High Vapor Uptake Capacity and Robust Cycling Stability
      for Potential Applications in Advanced Adsorption Heat Pumps.
AB  - Modular and compact adsorption heat pumps (AHPs) promise an energy-efficient
      alternative to conventional vapor compression based heating, ventilation and air
      conditioning systems. A key element in the advancement of AHPs is the development
      of adsorbents with high uptake capacity, fast intracrystalline diffusivity and
      durable hydrothermal stability. Herein, the ion exchange of NaY zeolites with
      ingoing Mg2+ ions is systematically studied to maximize the ion exchange degree
      (IED) for improved sorption performance. It is found that beyond an ion exchange
      threshold of 64.1%, deeper ion exchange does not benefit water uptake capacity or
      characteristic adsorption energy, but does enhance the vapor diffusivity. In
      addition to using water as an adsorbate, the uptake properties of Mg,Na-Y
      zeolites were investigated using 20 wt.% MeOH aqueous solution as a novel anti
      freeze adsorbate, revealing that the MeOH additive has an insignificant influence
      on the overall sorption performance. We also demonstrated that the labscale
      synthetic scalability is robust, and that the tailored zeolites scarcely suffer
      from hydrothermal stability even after successive 108-fold adsorption/desorption
      cycles. The samples were analyzed using N2 sorption, 27Al/29Si MAS NMR
      spectroscopy, ICP-AES, dynamic vapor sorption, SEM, Fick's 2nd law and D-R
      equation regressions. Among these, close examination of sorption isotherms for
      H2O and N2 adsorbates allows us to decouple and extract some insightful
      information underlying the complex water uptake phenomena. This work shows the
      promising performance of our modified zeolites that can be integrated into
      various AHP designs for buildings, electronics, and transportation applications.

PMID- 25395878
TI  - State Investments in Psychiatric Innovation: Investigating Unmeasured State
      Factors.
AB  - We apply three separate panel data estimation methods to examine the diffusion of
      technologies at the state-level. These methods include the Hausman-Taylor random
      effects model, the fixed effects vector decomposition (FEVD), and generalized
      estimating equations (GEE). We discuss the assumptions required of each and
      assess the stability of our policy results across the three models for a
      longitudinal study of the diffusion of newer psychotropic technologies. We find a
      reasonable level of consistency among marginal effects for time varying
      independent variables between our three estimation methods but some discrepancy
      in the estimated measure of precision in our empirical application. We find a
      number of policy conclusions are quite stable across estimation methods and may
      be of interest to state-level mental health policy decision makers.

PMID- 25395879
TI  - Enantiospecific Synthesis and Biological Investigations of a Nuphar Alkaloid:
      Proposed Structure of a Castoreum Component.
AB  - An enantiospecific synthesis of a Nuphar alkaloid was achieved in 9 steps from N
      Boc-(L)-proline. The alkaloid is a minor component of castoreum, the dried scent
      glands of the beaver. During the course of our study, the stereochemistry of
      three synthetic intermediates was verified by X-ray analysis, which contributes
      to resolving existing discrepancies among the literature reports regarding the
      synthesis of this particular compound. Based on our synthesis, we propose the
      structure of the natural product. Also, intrigued by castoreum's therapeutic
      effect, which was used in ancient Greece and Rome for gynecological and other
      purposes, biological screening was conducted. We found that the alkaloid has
      affinity for the oxytocin receptor.

PMID- 25395880
TI  - Esophageal cancer: Recent advances in screening, targeted therapy, and
      management.
AB  - The incidence of esophageal cancer remains on the rise worldwide and despite
      aggressive research in the field of gastrointestinal oncology, the survival
      remains poor. Much remains to be defined in esophageal cancer, including the
      development of an effective screening tool, identifying a good tumor marker for
      surveillance purposes, ways to target esophageal cancer stem cells as well as
      circulating tumor cells, and developing minimally invasive protocols to treat
      early-stage disease. The goal of this chapter is to highlight some of the recent
      advances and ongoing research in the field of esophageal cancer. 

PMID- 25395881
TI  - Effect of diet education on blood pressure changes and interdialytic weight in
      hemodialysis patients admitted in hajar hospital in shahrekord.
AB  - BACKGROUND AND AIM: Nutrition is a key factor in the treatment of patients with
      chronic kidney disease because kidney burden decrease causes uremic reduction and
      its side effects. The aim of this research is to examine the effect of diet
      education on blood pressure changes and interdialytic weight in Hemodialysis
      patients admitted to Hemodialysis ward of Hajar hospital in Shahrekord. METHODS:
      This quasi-experimental and interventional study of 100 dialysis patients
      referred to Hemodialysis ward of Hajar hospital was performed in a pre-test and
      post-test in 2011. Diet education, including face to face training with
      instruction booklets, were conducted in the two sessions. Having carried out the
      educational program, blood pressure and interdialytic weight gain were measured
      and recorded one month before and during three stages and after the educational
      program by researcher-designed checklists. The data were analyzed through SPSS 16
      software by Paired t-test and ANOVA. RESULTS: The results showed that mean of
      primary weight of the patients increase from 66.15+/-15.10 to 64.43+/-14.67. Mean
      of Systolic and diastolic blood pressure in patients in three stages were reduced
      to 6.65+/-1.51 mmg 2.24+/-1.82 mmg respectively. There was a significant
      difference between the creatinine amount in patients before and after of training
      (p<=0.01) but no meaningful difference was observed between the BUN amount before
      and after of training (p<=0.031). CONCLUSION: training to patients underwent
      hemodialysis in order to observe diet and its effects on improvement in treatment
      are of significant importance.

PMID- 25395882
TI  - The importance of neutrophil lymphocyte ratio in patients with psoriasis.
AB  - OBJECTIVE: The aim of this study is to assess the neutrophil lymphocyte ratio
      (NLR) as an inflammatory marker in patients with psoriasis and to compare it with
      healthy subjects and to evaluate the correlation with the severity of the
      disease. METHODS: 104 psoriasis patients and 70 healthy persons were included as
      the control group. The laboratory results were recorded retrospectively from the
      patients' files and controls. NLR was calculated by the division of the
      neutrophil count to the lymphocyte count in the hemogram test. The dermatology
      examinations and psoriatic area severity index (PASI) scoring were performed by
      the same dermatologist. RESULTS: Leukocyte, neutrophil, NLR levels of the
      psoriasis patients were significantly elevated compared to those of the control
      group (p<0.05, p<0.01 and p<0.01 respectively). There were no correlation between
      NLR and PASI score (p>0.05) in the patient group. CONCLUSIONS: NLR, an emerging
      marker of inflammation, is higher in patients with psoriasis. Therefore we have
      suggested that this marker can be used for following of the psoriasis patients.

PMID- 25395883
TI  - Analysis of human papillomavirus and herpes simplex virus genus -2 from patients
      with cervical cancer in isfahan, iran.
AB  - BACKGROUND: Although cervical uterine cancer is a second form of cancer among
      women, but it occupies fifth form among all cancer types. METHODS: In the present
      study, human papillomavirus (HPV) and herpes simplex virus 2 (HSV-2) in cervical
      cancer patients by using real time polymerase chain reaction (PCR) technique and
      the relation between their viral loads were investigated. 156 cervical carcinoma
      tissues were collected from married women in health centers in Isfahan, Iran.
      RESULTS: The results showed that among 156 specimens, 58.97%, 45.51% and 7.05%
      were positive for HPV DNA, HPV-16 and HPV-18 respectively. Only in 2.3%
      specimens, HSV-2 and HPV-16 were positively detected where viral load HSV-2 in
      conjunction with HSV-16 dramatically increased. CONCLUSION: Thus the present
      study not only confirmed that viral load of HPV-16 is more than other HPV types,
      but also in possible conjunction with HSV-2, both rates will significantly
      increase.

PMID- 25395884
TI  - The connection between endourological procedures and occurrence of urinary
      infections.
AB  - INTRODUCTION: Endoscopic surgery and endourological procedures imply the use of
      special instruments that are introduced into the urinary system through the
      urethra and percutaneous techniques that allow ante grade access to the urinary
      tract. The risk of urinary tract infection after endourological procedures and
      the use of antibiotic prophylaxis for these procedures is a question about which
      there is no unique opinion. GOAL: The objective of this study was to determine
      the connection between endourological procedures and occurrence of urinary
      infections and to analyze the risk factors of urinary infection for patients who
      were hospitalized at the Urology Clinic of the Clinical Center University of
      Sarajevo (CCUS). MATERIAL AND METHODS: The research was conducted as a
      prospective study on a sample of 208 patients of both genders, who were
      hospitalized at the Urology Clinic of the CCUS and to whom one of endourological
      procedures was indicated either for diagnostic or therapeutic purposes. All
      patients were clinically examined prior to endoscopic procedures and after the
      treatment attention was focused on the symptoms of urinary tract infections.
      RESULTS: Analysis of the presence of postoperative bacteriuria shows that it has
      been more common in men or in 48 cases (28.1%) compared to women with 8 cases
      (21.6%) (p>0.05). Preoperative catheterization was statistically significantly
      more present in patients who have had a postoperative bacteriuria (16 or 28.6%)
      compared to those without bacteriuria (8 or 5.3%) (p<0.05). Analysis of the
      average duration of postoperative catheterization shows that patients with
      postoperative bacteriuria had longer duration of postoperative cauterization of
      1.97+/-0.14 days (range 1-20 days) compared to those without postoperative
      bacteriuria with 1.4+/-0.4 days (range 0-5 days) and with a statistically
      significant difference (p<0.05). Antibiotic prophylaxis in relation to the
      occurrence of postoperative bacteriuria did not show a statistically significant
      difference (p> 0.05). Analysis of the correlation coefficient indicates that a
      statistically significant effect on the occurrence of postoperative bacteriuria
      have preoperative bacteriuria, duration of postoperative catheterization and
      duration of hospital stay, as well as the total duration of hospitalization
      before and after endourological treatment (p<0.05). CONCLUSION: It is important
      to emphasize that the endourological procedures are safe procedures in terms of
      urinary tract infections. This study should lay pathway to establishment of
      guidelines for the application of antibiotic prophylaxis in endourological
      procedures. This would standardize the perioperative use of antibiotics, taking
      into account the local prevalence of pathogens and antibiotic resistance, but
      keeping the individual approach to each patient, considering all risk factors for
      the development of urinary infection after endourological procedures..

PMID- 25395885
TI  - Comparison of treatment results for fractures of the distal humerus in children
      according to the indication for conservative or surgical solution.
AB  - INTRODUCTION: Records about the fractures of the distal humerus could be founds
      in the scriptures written long before Christ (Hippocrates 300 to 400 BC). During
      the twilight of science development and of any scientific work (the Middle Ages),
      little has been written about this problem. Between the 1700 and 1800 much was
      discussed about the controversies between the correct position and
      immobilization. In the early twentieth century view on the treatment of fractures
      of the distal humerus begins to change dramatically, from the former passive to
      active surgical treatment. The sudden turnaround followed thanks to the intensive
      development of technology, especially new imaging technology. MATERIAL AND
      METHODS: We observed a period of 4 (four) years (1998 to 2002), and only hospital
      patients of certain age. As database are used the histories of the disease. The
      patients were followed for one year and at the same time, we analyzed (clinical)
      early complications after three (3) months and late complications (X ray), after
      a year. Among the early complications we observed most often lower motility and
      contraction, and of late we have followed the morphological deformation-cubitus
      varus and valgus. RESULTS: Using x-ray images, we measured Baumann's (en face)
      and lateral condylar angle (profile) after one year in the operated group and the
      group treated conservatively SPDH type III in children. We calculated the
      arithmetic mean (x) and a standard deviation (SD) in both groups. Using chi
      square and t-test, with the probability of 95%, we showed that there is a
      significant difference between operative and conservative treatment of SPDH type
      III in children, according to Gartland. CONCLUSION: All humerus fracture type-III
      by Gartland in children should be surgically treated. Surgery should be
      undertaken in a time frame of 6 hours. Surgery should be done in these cases by
      the specialized institutions (Clinical Hospital Centre). The success of treatment
      in such institutions corresponds to the results achieved in the world (93.0%). We
      must be sure to adopt and implement a scheme of treatment of fractures of the
      distal humerus in children. Required is faint trail, OPF, lateral (Kaplan)
      approach, exceptionally for some articular fractures posterior approach by
      Campbell, fixation with two or more Kirchner's needles, usually cross-set at an
      angle of 30 degrees , vacuum drainage with cast immobilization.

PMID- 25395886
TI  - Optic neuritis as first clinical manifestations the multiple sclerosis.
AB  - AIM: To analyze the clinical signs of multiple sclerosis (MS) and show that optic
      neuritis is one of the first event, which indicates the development of disease.
      PATIENTS AND METHODS: The study involved 89 cases in which it confirmed MS at the
      time of the March 2009-2011. Since ophthalmological parameters were analyzed
      visual acuity (VA), visual field (VF), and retinal nerve fibre layer (RNFL)
      thickness of peripapillary rim by optic coherent tomography (OCT). RESULTS:
      Ten(10) patients had ON as the first clinical manifestation of the disease which
      was statistically significant (X(2) =9,7 p=0,01) compared to the manifestation of
      other clinical signs of disease. In VF, centrocecal scotomas were predominant in
      50% of the subjects; the RNFL thinning of the neuroretinal rim was verified in
      all patients, most often in the upper quadrant. A month after pulse
      corticosteroid therapy, visual acuity in all patients with ON ranged from 0.6 to
      1.0. CONCLUSION: ON is one of the first MS clinical manifestation. In VF, the
      most common disturbances are in the centrocecal area. The RNFL thinning was
      verified in all patients with OCT.

PMID- 25395887
TI  - Work ability index, absenteeism and depression among patients with burnout
      syndrome.
AB  - GOAL: The aim of this study is to estimate the association of burnout syndrome
      and depression; burnout syndrome and sick leave; and burnout syndrome with Work
      Ability Index in patients who suffer from stress at work. MATERIAL AND METHODS:
      The control clinical study was conducted in the Teaching Department for
      Professional Pathology and Toxicology at the Primary Health Care Center Tuzla in
      the period from 2009 to 2014. The study included 140 patients exposed to
      different levels of stress at work. Besides conducted interviews and anamnesis
      with working anamnesis, physical examination, all patients were subjected to
      diagnostic package of questionnaires for assessing exposure to stress at work and
      its effects on health and work ability and Hamilton Rating Scale for screening
      depression. All patients were referred to the Department with suspected distress
      and burnout syndrome. For this study we used a questionnaire for measuring
      intensity of burnout (two categories exclude suffering from burnout syndrome:
      successfully overcome stress at work and sometimes feel stress at work and the
      other two reveal the initial and very high burn-out syndrome. Studied group was
      consisted of patients categorized with burnout syndrome (n=88). RESULTS: The
      questionnaire on the Work Ability Index (WAI) estimated characteristics of sick
      leave and prognostic factors with current work ability index. Lack of support at
      work with poor personal relations is the most common factor with the mobbing in
      burnout syndrome. Significantly more patients with the burnout syndrome suffered
      very severe depression 49%:37%; more use long sick leaves 53%:21%; several of
      them have poor WAI 51%:31% compared to those who are only exposed to stress at
      work (p=0.001). We found that the burn-out syndrome is predictor for developing
      depression (beta=0.312, 95% CI, 0.114-0.353, p=0.001); absenteeism (beta=0.285,
      95% CI, 0.093-0.334, p=0.001); and a decline in working ability (beta=0.413, 95%
      CI, 0.297-0.648). All the patients in whom it is found burnout syndrome is to
      provide medical and non-medical assistance in order to achieve stabilization of
      health and positive work orientation, mental rehabilitation and reintegration at
      work place. CONCLUSION: The process involves serious emergency measures in work
      organization which include improved in working environment, communication and
      combat against mobbing.

PMID- 25395888
TI  - Prevalence, gender distribution and presence of attention deficit hyperactivity
      disorder by certain sociodemographic characteristics among university students.
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a
      neurobehavioral developmental disorder usually diagnosed in children, with
      appearance of the first symptoms before the age of seven years. The disorder is
      characterized by inattention and/or impulsivity and hyperactivity that can
      seriously affect many aspects of behavior and performance at school. Specific
      sociodemographic characteristics seem to contribute to the appearance of ADHD.
      MATERIAL AND METHODS: The study was done on a sample of 500 university students.
      For the measurement of ADHD symptoms, the ADHD Adult Self-report Scale was used
      and a specifically designed questionnaire for collecting sociodemographic data.
      RESULTS: The results of this screening study showed that in 184 (48.7%)
      respondents the symptoms of the disorder in the activity and attention were
      registered. ADHD is highly significant associated with gender (p = 0.0004). Men
      more often than women have this kind of disorder. Our results also showed that
      living and material conditions were not associated with a higher prevalence of
      ADHD.

PMID- 25395889
TI  - Erythema at BCG Inoculation Site in Kawasaki Disease Patients.
AB  - INTRODUCTION: Kawasaki disease is an acute, self-limiting childhood systemic
      vasculitis with unknown etiology. Because there is no diagnostic test for
      Kawasaki disease, the diagnosis is based on clinical criteria. An important
      clinical sign that is not included in the classical clinical criteria for
      Kawasaki disease is a reaction at the Bacille Calmette-Guerin inoculation site
      that are present in about 30-50% of Kawasaki disease patients. THE AIM: of this
      review was to highlight the usefulness of the inflammation at the Bacille
      Calmette-Guerin inoculation site for early diagnosis of Kawasaki disease, we
      conducted a literature review on Medline in PubMed area, Google scholar, Magiran
      and Scientific Information Database using the search terms "Kawasaki disease,
      Erythema, BCG, inoculation site, children, cardiac complications, coronary artery
      lesion, aneurysm, incomplete Kawasaki in 2013. RESULTS AND DISCUSSION: A total of
      15 articles had been found. Erythema at the Bacille Calmette-Guerin inoculation
      site was found in 49.87% of Kawasaki disease patients. Coronary artery
      abnormalities were found in 10.3% of cases. According to this review, BCGitis is
      more prevalent than cervical lymphadenopathy and rash and it can be a useful
      criterion in the diagnosis of incomplete Kawasaki disease in cases not fulfills
      the classic criteria of at least four of the five findings.

PMID- 25395890
TI  - Epidemiology of goiter and benign tumors of the thyroid gland in Albania.
AB  - AIM: The aim of this study was to describe the demographic characteristics and
      disease patterns among patients with thyroid nodular abnormalities (goiter) and
      benign tumors of the thyroid gland in Albania, a transitional country in South
      Eastern Europe. METHODS: Our study included all patients diagnosed with goiter
      and/or benign tumors of the thyroid gland who were hospitalized at the University
      Hospital Center (UHC) "Mother Teresa" in Tirana between 2004 and 2012 (N=2258).
      All patients underwent the same examination and interviewing procedures.
      Demographic characteristics included gender, age, and place of residence. Binary
      logistic regression was used to compare the demographic characteristics between
      patients with benign tumors of the thyroid gland and those with goiter. RESULTS:
      Overall, there were 2204 patients with goiter and 54 patients with benign tumors
      of the thyroid gland hospitalized at UHC over the period 2004-2012. There was no
      evidence of statistically significant differences in demographic characteristics
      (age, gender, or place of residence) between patients with benign tumors of the
      thyroid gland and those with goiter. CONCLUSIONS: Our study provides useful
      evidence on the epidemiology of benign tumors of the thyroid gland and the
      thyroid nodular abnormalities (goiter) in the Albanian population. Future studies
      in Albania should assess the main determinants of thyroid gland disorders and
      compare them with findings pertinent to other similar populations.

PMID- 25395891
TI  - Social Determinants of Self-reported Health Among Population in Republic of
      Macedonia - Results from a Case-control Study.
AB  - INTRODUCTION: Studying self-reported health is considered an indicator for
      morbidity and mortality that may be used in primary health care to detect poor
      health in certain population groups that predicts health care utilization. GOAL:
      The goal of the survey is to assess the socioeconomic self-rated health gradient
      and to describe contribution of behavioral risk factors to this gradient among
      population in Republic of Macedonia. MATERIAL AND METHODS: Data is collected
      through a "nested case-control study", conducted in the period March - December,
      2013. "Cases" are households with TB patient(s) registered in the period July,
      2012 - June, 2013 and "controls" are households randomly chosen in cases'
      immediate vicinity. RESULTS: The total study population is 562 households with
      total of 2720 respondents. Self-rated health was reported as excellent or good by
      only half of the respondents, with slightly less positive answers among cases
      compared to controls and evident differences in responses for poor or extreme
      difficulties in everyday life. Positive association was found between poor rated
      health and long-standing diseases and education was associated with poor self
      rated health. Adding questions on mobility, self-care, pain, cognition,
      interpersonal activities and affect has only reaffirmed the findings, with
      statistically significant differences among study groups along all six
      dimensions. CONCLUSION: The ease of use of simple questions to ask for self-rated
      health makes it an extremely beneficial tool in health care planning.

PMID- 25395892
TI  - Prevalence and Correlates of Drug-drug Interactions in the Regional Hospital of
      Gjilan, Kosovo.
AB  - AIM: Our aim was to assess the prevalence and socioeconomic and clinical
      correlates of drug-drug interactions among the adult population of transitional
      Kosovo. METHODS: A cross-sectional study was conducted including a representative
      sample of 1921 patients aged >=18 years (mean age: 57.8+/-11.2 years; 50.3%
      women; overall response: 96%) from the regional hospital of Gjilan, Kosovo,
      during 2011-2013. Potential drug-drug-interactions were assessed and clinical
      data as well as demographic and socioeconomic information were collected. Binary
      logistic regression was used to assess the correlates of drug-drug interactions.
      RESULTS: Upon multivariable adjustment for all the demographic and socioeconomic
      factors as well as the clinical characteristics, drug-drug interactions were
      positively and significantly related to older age (OR=2.1, 95%CI=1.3-2.8), a
      lower educational attainment (OR=1.4, 95%CI=1.1-1.9), a longer hospitalization
      period (OR=2.7, 95%CI=2.1-3.6), presence of three groups of diseases [infectious
      diseases (OR=1.7, 95%CI=1.3-2.4), cardiovascular diseases (OR=1.8, 95%CI=1.4
      2.6), respiratory diseases (OR=1.6, 95%CI=1.2-2.5)], presence of comorbid
      conditions (OR=3.2, 95%CI=2.3-4.4) and an intake of at least four drugs (OR=5.9,
      95%CI=4.6-7.1). CONCLUSIONS: Our study provides important evidence on the
      prevalence and socioeconomic and clinical correlates of drug-drug interactions
      among the hospitalized patients in the regional hospital of Gjilan, Kosovo.
      Findings from our study should raise the awareness of decision-makers and policy
      makers about the prevalence and determinants of drug-drug interactions in the
      adult population of post-war Kosovo.

PMID- 25395893
TI  - Influence of age on the survival and mortality rate in acute caustic poisonings.
AB  - OBJECTIVE: Acute poisonings with caustic substances can cause severe chemical
      injuries to the upper gastrointestinal tract, which can be localized from the
      mouth to the small intestines. They are seen very often among young people in
      their most productive years. The aim of this study is to examine the influence of
      patient's age on the mortality rate and survival of patients with acute caustic
      poisonings, and also to analyze their correlation. MATERIAL AND METHODS: We
      studied medical records from 415 patients, aged between 14 and 90 years, who were
      hospitalized and treated at the University Clinic for toxicology and urgent
      internal medicine, Skopje, Republic of Macedonia, in the period between 2007 and
      2011. RESULTS: In the survey we included 415 patients with acute corrosive
      poisonings, from which 295 (71.08%) were females and 120 (28. 92%) were males.
      388 (93.49%) from the total number of patients ingested the corrosive agent with
      suicidal attempt and 27 (6.5%) ingested it accidentally. CONCLUSION: Unregulated
      production, import, packing and labeling of various caustic agents, due to
      inappropriate legislative, made them one of the most often abused substances in
      everyday life, especially in developing countries where the number of caustic
      poisonings rises.

PMID- 25395894
TI  - Public health aspects of the family medicine concepts in South eastern europe.
AB  - INTRODUCTION: Family medicine as a part of the primary health care is devoted to
      provide continuous and comprehensive health care to the individuals and families
      regardless of age, gender, types of diseases and affected system or part of the
      body. Special emphasis in such holistic approach is given to the prevention of
      diseases and health promotion. Family Medicine is the first step/link between
      doctors and patients within patients care as well as regular
      inspections/examinations and follow-up of the health status of healthy people.
      Most countries aspire to join the European Union and therefore adopting new
      regulations that are applied in the European Union. AIM: The aim of this study is
      to present the role and importance of family medicine, or where family medicine
      is today in 21 Century from the beginning of development in these countries. The
      study is designed as a descriptive epidemiological study with data from 10
      countries of the former Communist bloc, Slovenia, Croatia, Bosnia and
      Herzegovina, Serbia, Montenegro, Macedonia, Kosovo, Albania, Bulgaria, Romania,
      Czech Republic, Slovakia and Hungary, just about half of them are members of the
      EU. We examined the following variables: socio-organizational indicators, health
      and educational indicators and health indicators. The data used refer to 2002 and
      as a source of data are used official data from reference WebPages of family
      medicine doctors associations, WONCA website (EURACT, EQuiP, EGPRN), WebPages of
      Bureau of Statistics of the countries where the research was conducted as well as
      the Ministries of Health. RESULTS: Results indicates that the failures and
      shortcomings of health care organizations in Southeast Europe. Lack of money
      hinders the implementation of health care reform in all mentioned countries, the
      most of them that is more oriented to Bismarck financing system. Problems in the
      political, legal and economic levels are obstacles for efficient a problem
      reconstructing health care system toward family medicine and primary prevention
      interventions. The population is not enough educated for complicated enforcement
      for and prevention of diseases that have a heavy burden on the budget. Health
      insurance and payment of health services is often a problem, because the patients
      must be treated regardless of their insurance coverage and financial situation.
      The decrease in production and economic growth, as well as low gross national
      income in the countries with economic crisis, lead to the inability of treatment
      for a large number of the population. Such situation a system leads to additional
      debts and loans to healthcare system. Measures implemented for provision of acute
      curative care largely did not lead to improvements in the health status of the
      population. Educational and preventive measures, as well as higher standards for
      quality and accessibility of health care services for entire population in each
      country, especially those struggling are bound to joining the European Union and
      their implementation must start. The most A large number of medical institutions
      are is inefficient in health education and health promotion and must work to
      educate patients and families and increase the quality of preventive health
      services. Modernization of health care delivery and joining the European Union by
      increasing overall economic stability of countries is one of the primary goals of
      all countries in Southeast Europe.

PMID- 25395895
TI  - How Can Next-Generation Sequencing (Genomics) Help Us in Treating Colorectal
      Cancer?
AB  - Next generation sequencing methods have exponentially increased the amount of
      genomic information available to scientists and clinicians. This review will
      explain the evolution of tumor gene sequencing and identify its potential to
      accelerate therapeutic progress by using colorectal cancer to illustrate the
      benefits of this type of analysis. A milestone in sequencing occurred when The
      Cancer Genome Atlas investigators characterized the genomes of 276 colorectal
      cancer samples, with the resulting information expected to provide future
      clinical applications and help to guide the treatment of colorectal cancer. Data
      regarding colorectal cancer mutational frequencies, prognostic and predictive
      biomarker usefulness, and signaling pathway alterations are emerging from various
      next generation sequencing platforms. Next generation sequencing methods are also
      enhancing our understanding of the causes and consequences of both the
      chromosomal instability and microsatellite instability pathways, as well as
      expanding our knowledge of the origins of familial colorectal cancer. Limitations
      to next generation sequencing methods include the need for storage and analysis
      of massive quantities of data, as well as assurance that the data is of the
      highest possible quality. However, this genomic technology carries with it the
      potential to revolutionize our treatment of colorectal cancer patients through
      better understanding of the underlying disease biology and subsequent development
      and application of therapeutic approaches targeting the genetic abnormalities
      specific to individual malignancies.

PMID- 25395896
TI  - Targeting Notch Signaling in Colorectal Cancer.
AB  - The activation of Notch signaling is implicated in tumorigenesis in the colon due
      to the induction of pro-survival signaling in colonic epithelial cells.
      Chemoresistance is a major obstacle for treatment and for the complete
      eradication of colorectal cancer (CRC), hence, the inhibition of Notch is an
      attractive target for CRC and several groups are working to identify small
      molecules or monoclonal antibodies that inhibit Notch or its downstream events;
      however, toxicity profiles in normal cells and organs often impede the clinical
      translation of these molecules. Dietary agents have gained momentum for targeting
      several pro-survival signaling cascades, and recent studies demonstrated that
      agents that inhibit Notch signaling result in growth inhibition in preclinical
      models of CRC. In this review, we focus on the importance of Notch as a
      preventive and therapeutic target for colon cancer and on the effect of WA on
      this signaling pathway in the context of colon cancer.

PMID- 25395897
TI  - Investigation of Vietnamese plants for potential anticancer agents.
AB  - Higher plants continue to afford humankind with many new drugs, for a variety of
      disease types. In this review, recent phytochemical and biological progress is
      presented for part of a collaborative multi-institutional project directed
      towards the discovery of new antitumor agents. The specific focus is on bioactive
      natural products isolated and characterized structurally from tropical plants
      collected in Vietnam. The plant collection, identification, and processing steps
      are described, and the natural products isolated from these species are
      summarized with their biological activities.

PMID- 25395899
TI  - Modeling thermophoretic effects in solid-state nanopores.
AB  - Local modulation of temperature has emerged as a new mechanism for regulation of
      molecular transport through nanopores. Predicting the effect of such modulations
      on nanopore transport requires simulation protocols capable of reproducing non
      uniform temperature gradients observed in experiment. Conventional molecular
      dynamics (MD) method typically employs a single thermostat for maintaining a
      uniform distribution of temperature in the entire simulation domain, and,
      therefore, can not model local temperature variations. In this article, we
      describe a set of simulation protocols that enable modeling of nanopore systems
      featuring non-uniform distributions of temperature. First, we describe a method
      to impose a temperature gradient in all-atom MD simulations based on a boundary
      driven non-equilibrium MD protocol. Then, we use this method to study the effect
      of temperature gradient on the distribution of ions in bulk solution (the
      thermophoretic effect). We show that DNA nucleotides exhibit differential
      response to the same temperature gradient. Next, we describe a method to directly
      compute the effective force of a thermal gradient on a prototypical biomolecule-a
      fragment of double-stranded DNA. Following that, we demonstrate an all-atom MD
      protocol for modeling thermophoretic effects in solid-state nanopores. We show
      that local heating of a nanopore volume can be used to regulate the nanopore
      ionic current. Finally, we show how continuum calculations can be coupled to a
      coarse-grained model of DNA to study the effect of local temperature modulation
      on electrophoretic motion of DNA through plasmonic nanopores. The computational
      methods described in this article are expected to find applications in rational
      design of temperature-responsive nanopore systems.

PMID- 25395898
TI  - Oleanane triterpenoids in the prevention and therapy of breast cancer: current
      evidence and future perspectives.
AB  - Breast cancer is one of the most frequently diagnosed cancers and major cause of
      death in women in the world. Emerging evidence underscores the value of dietary
      and non-dietary phytochemicals, including triterpenoids, in the prevention and
      treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic
      triterpenoid, is present in a large number of dietary and medicinal plants.
      Oleanolic acid and its derivatives exhibit several promising pharmacological
      activities, including antioxidant, anti-inflammatory, hepatoprotective,
      cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and
      antiviral effects. Numerous studies indicate that oleanolic acid and other
      oleanane triterpenoids modulate multiple intracellular signaling pathways and
      exert chemopreventive and antitumor activities in various in vitro and in vivo
      model systems. A series of novel synthetic oleanane triterpenoids have been
      prepared by chemical modifications of oleanolic acid and some of these compounds
      are considered to be the most potent anti-inflammatory and anticarcinogenic
      triterpenoids. Accumulating studies provide extensive evidence that synthetic
      oleanane derivatives inhibit proliferation and induce apoptosis of various cancer
      cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal
      models of blood, breast, colon, connective tissue, liver, lung, pancreas,
      prostate and skin cancer. This review critically examines the potential role of
      oleanolic acid, oleanane triterpenoids and related synthetic compounds in the
      chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo
      studies on these agents and related molecular mechanisms are presented. Several
      challenges and future directions of research to translate already available
      impressive preclinical knowledge to clinical practice of breast cancer prevention
      and therapy are also presented.

PMID- 25395900
TI  - Cost of illness due to typhoid Fever in pemba, zanzibar, East Africa.
AB  - The aim of this study was to estimate the economic burden of typhoid fever in
      Pemba, Zanzibar, East Africa. This study was an incidence-based cost-of-illness
      analysis from a societal perspective. It covered new episodes of blood culture
      confirmed typhoid fever in patients presenting at the outpatient or inpatient
      departments of three district hospitals between May 2010 and December 2010. Cost
      of illness was the sum of direct costs and costs for productivity loss. Direct
      costs covered treatment, travel, and meals. Productivity costs were loss of
      income by patients and caregivers. The analysis included 17 episodes. The mean
      age of the patients, was 23 years (range=5-65, median=22). Thirty-five percent
      were inpatients, with a mean of 4.75 days of hospital stay (range=3-7,
      median=4.50). The mean cost for treatment alone during hospital care was US$
      21.97 at 2010 prices (US$ 1=1,430.50 Tanzanian Shilling?TSH). The average
      societal cost was US$ 154.47 per typhoid episode. The major expenditure was
      productivity cost due to lost wages of US$ 128.02 (83%). Our results contribute
      to the further economic evaluation of typhoid fever vaccination in Zanzibar and
      other sub-Saharan African countries. 

PMID- 25395901
TI  - Educational Intervention among Barbers to Improve Their Knowledge regarding
      HIV/AIDS: A Pilot Study from a South Asian Country.
AB  - One of the Millennium Development Goals is to combat HIV, the burden of which
      continues to increase in developing countries, like Pakistan. The prevalence is
      high among the high-risk population, and the use of unsterilized surgical
      instruments, traditional straight razors, and blades adds to the spread of this
      disease. This study assesses the effect of an educational intervention on the
      knowledge of 70 barbers practising in a suburban community in Pakistan regarding
      HIV and its symptoms and transmission. At baseline, only 10% of the barbers
      reported that they had ever heard about HIV compared to 49% after the
      intervention. Similarly, 4% and 6% of them had good knowledge at baseline about
      symptoms and transmission of the disease, increasing to 39% and 43% respectively,
      after the intervention (p<0.001). The results of this educational intervention
      warrant consideration of activation of mass campaigns to increase public
      awareness about bloodborne diseases and to educate personnel who might harm the
      persons in their communities by unsafe practices. 

PMID- 25395902
TI  - Microbial evaluation of fresh, minimally-processed vegetables and bagged sprouts
      from chain supermarkets.
AB  - The aim of this study was to evaluate the bacterial and fungal quality of
      minimally-processed vegetables (MPV) and sprouts. A total of 116 samples of fresh
      cut vegetables, ready-to-eat salads, and mung bean and wheat sprouts were
      randomly collected and analyzed. The load of aerobic mesophilic bacteria was
      minimum and maximum in the fresh-cut vegetables and fresh mung bean sprouts
      respectively, corresponding to populations of 5.3 and 8.5 log CFU/g. E. coli
      O157:H7 was found to be absent in all samples; however,  other E. coli strains
      were detected in 21 samples (18.1%), and Salmonella spp. were found in one mung
      bean (3.1%) and one ready-to-eat salad sample (5%). Yeasts were the predominant
      organisms and were found in 100% of the samples. Geotrichum, Fusarium, and
      Penicillium spp. were the most prevalent molds in mung sprouts while Cladosporium
      and Penicillium spp. were most frequently found in ready-to-eat salad samples.
      According to results from the present study, effective control measures should be
      implemented to minimize the microbiological contamination of fresh produce sold
      in Tehran, Iran. 

PMID- 25395903
TI  - Determinants of malnutrition and post-operative complications in hospitalized
      surgical patients.
AB  - The study aimed to determine the nutritional status (NS) of hospitalized surgical
      patients and investigate a possible association between NS and type of disease,
      type of surgery and post-operative complications. The gender, age, disease,
      surgery, complications, length of hospital stay, number of medications,
      laboratory test results, and energy intake of 388 hospitalized surgical patients
      were recorded. NS was determined by classical anthropometry. The inclusion
      criteria were: nutritional status assessment done within the first 24 hours of
      admission, age >= 20 years, and complete medical history. Univariate and multiple
      Cox's regression analyses were employed to determine which variables were
      possible risk factors of malnutrition and complications. Malnutrition was more
      common in males (p=0.017), individuals aged 70 to 79 years (p=0.000), and
      individuals with neoplasms and digestive tract diseases (p=0.000). Malnourished
      individuals had longer hospital stays (p=0.013) and required more medications
      (p=0.001). The risk of malnutrition was associated with age and disease.
      Individuals aged 70 years or more had a two-fold increased risk of malnutrition
      (p=0.014; RR=2.207; 95% CI 1.169-4.165); those with neoplasms (p=0.008;
      RR=14.950; 95% CI 2.011-111.151) and those having digestive tract diseases
      (p=0.009; RR=14.826; 95% CI 1.939-113.362) had a 14-fold increased risk of
      malnutrition. Complications prevailed in older individuals (p=0.016), individuals
      with longer hospital stays (p=0.007), and individuals who died (p=0.002). The
      risk of complications was associated with age and BMI. In the present study, the
      risk of malnutrition was associated with age and type of disease; old age and low
      BMI may increase complications.

PMID- 25395904
TI  - Waist-to-height ratio percentiles and cutoffs for obesity: a cross-sectional
      study in brazilian adolescents.
AB  - This study aimed to describe the distribution of waist-to-height ratio (WHtR)
      percentiles and cutoffs for obesity in Brazilian adolescents. A cross-sectional
      study including adolescents aged 10 to 15 years was conducted in the city of Sao
      Paulo, Brazil; anthropometric measurements (weight, height, and waist
      circumference) were taken, and WHtRs were calculated and then divided into
      percentiles derived by using Least Median of Squares (LMS) regression. The
      receiver operating characteristic (ROC) curve was used in determining cutoffs for
      obesity (BMI >= 97th percentile) and Mann-Whitney and Kruskal-Wallis tests were
      used for comparing variables. The study included 8,019 adolescents from 43
      schools, of whom 54.5% were female, and 74.8% attended public schools. Boys had
      higher mean WHtR than girls (0.45 +/- 0.06 vs 0.44 +/- 0.05; p=0.002) and higher
      WHtR at the 95th percentile (0.56 vs 0.54; p<0.05). The WHtR cutoffs according to
      the WHO criteria ranged from 0.467 to 0.506 and 0.463 to 0.496 among girls and
      boys respectively, with high sensitivity (82.8-95%) and specificity (84-95.5%).
      The WHtR was significantly associated with body adiposity measured by BMI. Its
      age-specific percentiles and cutoffs may be used as additional surrogate markers
      of central obesity and its co-morbidities.

PMID- 25395905
TI  - Nutrition education based on health belief model improves dietary calcium intake
      among female students of junior high schools.
AB  - This study examined the effects of a nutrition education programme based on the
      Health Belief Model (HBM) on knowledge, attitude, and practice (KAP) of dietary
      calcium in female students. In this interventional study, 188 students were
      placed into intervention (95) and control (93) groups. The intervention group
      participated in a nutrition education programme. Students in both the groups
      completed KAP and food frequency questionnaire (FFQ) at baseline and after two
      and three months of follow-up respectively. The data were analyzed by independent
      and paired t-tests. Those who received the intervention were found to have better
      attitude (p=0.049) and practice (p=0.005) scores compared to the controls. The
      HBM constructs, including perceived susceptibility (p=0.006), perceived severity
      (p=0.001), perceived benefits (p=0.002), perceived barriers (p=0.001), and taking
      health action (p=0.02) scores, were also significantly higher. The findings
      support the effectiveness of nutrition education based on the HBM in improving
      the knowledge, attitude, and practice relating to calcium intake among adolescent
      students. 

PMID- 25395906
TI  - Leaf concentrate fortification of antenatal protein-calorie snacks improves
      pregnancy outcomes.
AB  - Ready-to-eat (RTE) snacks are routinely distributed to pregnant women in India.
      These provide protein and calories but are low in micronutrients. We investigated
      whether RTE snacks fortified with leaf concentrate (LC) could improve pregnancy
      outcomes, including maternal haemoglobin (Hb) concentrations and infants'
      birthweight. This randomized controlled two-arm trial was conducted over 18
      months: control (sRTE) group received standard 120 g RTE snack (102 g wheat
      flour, 18 g soya flour); intervention (lcRTE) group received the same snack
      fortified with 7 g LC. The study was conducted in Jaipur, Rajasthan, India. One
      hundred and five pregnant women aged 18-35 years were studied. Among the 105
      women randomized to the two arms of the trial, 2 (1.9%) were severely anaemic (Hb
      <= 6.0 g/dL); 55 (53.4%) were moderately anaemic (Hb 6.0-8.0 g/dL); 34 (33.0%)
      were mildly anaemic (Hb 8.6-10.9 g/dL); and 12 (11.7%) were not anaemic (Hb >=
      11.0 g/dL). In the final month of pregnancy, 83.0% (39/47) of women in the sRTE
      group had Hb <= 8.5 g/dL compared to 37.8% (17/45) in the lcRTE group (p<0.001).
      After adjustment for age and baseline Hb concentration, the difference in Hb
      concentrations due to LC fortification was 0.94 g/dL (95% CI 6.8-12.0; p<0.001).
      Mean live birthweight in the lcRTE group was 2,695 g (SD 325 g) compared to 2,545
      g (297 g) in the sRTE group (p=0.02). The lcRTE snacks increased infants'
      birthweight by 133.7 g (95% CI 7.3-260.2; p=0.04) compared to sRTE snacks. Leaf
      concentrate fortification of antenatal protein-calorie snacks in a low-income
      setting in India protected against declining maternal haemoglobin concentrations
      and increased infants' birthweight when compared with unfortified snacks. These
      findings require replication in a larger trial.

PMID- 25395907
TI  - Practices and challenges of growth monitoring and promotion in ethiopia: a
      qualitative study.
AB  - The use of growth monitoring and promotion (GMP) has become widespread. It is a
      potential contributor towards achieving the Millennium Development Goals of
      halving hunger and reducing child mortality by two-thirds within 2015. Yet, GMP
      appears to be a prerequisite for good child health but several studies have shown
      that there is a discrepancy between the purpose and the practice of GMP. The high
      prevalence of malnutrition in many developing countries seems to confirm this
      fact. A descriptive qualitative study was carried out from April to September
      2011. Focus group discussions and in-depth interviews were conducted amongst
      mothers and health workers. Data were analyzed using a qualitative content
      analysis technique, with the support of ATLAS.ti 5.0 software. The results
      suggest that most mothers were aware of the need for regular weight monitoring
      while health workers also seemed to be well-aware and to practise GMP according
      to the international guidelines. However, there was a deficit in maternal
      knowledge with regard to child-feeding and a lack of basic resources to keep
      and/or to buy healthful and nutritionally-rich food. Furthermore, the role of the
      husband was not always supportive of proper child-feeding. In general, GMP is
      unlikely to succeed if mothers lack awareness of proper child-feeding practices,
      and if they are not supported by their husbands. 

PMID- 25395908
TI  - Food adulteration and consumer awareness in Dhaka City, 1995-2011.
AB  - We conducted this study to investigate the magnitude of food adulteration during
      1995-2011 and consumer awareness in Dhaka city. We reviewed results of food
      sample testing by Public Health Food Laboratory of Dhaka City Corporation,
      Bangladesh Standards and Testing Institution, Consumers Association of Bangladesh
      publications, reports from lay press, including those on mobile magistrate court
      operations. We conducted a cross-sectional survey among 96 residents of Dhaka
      city, using a structured questionnaire in 2006. The overall proportion of food
      samples adulterated decreased during 2001-2005, and 40-54% of daily-consumed food
      was adulterated during 1995-2011. More than 35 food items were commonly
      adulterated. Consumers considered expiry date and quality or freshness as the
      best criteria while buying packaged and open food items respectively; only 11
      (12%) respondents considered approval of regulatory authority for buying packaged
      food items. More than half of the food consumed in Dhaka city is adulterated,
      which warrants actions by the Government, the industry, and the consumers. 

PMID- 25395909
TI  - Funds for treatment of hospitalized patients: evidence from Bangladesh.
AB  - This study was designed to explore sources of funds for health expenditure of
      patients if they are hospitalized. We have included 379 patients of 3 private and
      7 public hospitals to estimate total expenditure. Of them, 229 (60.4%) were from
      public and 150 (39.6%) from private hospitals. Mean expenditure was Tk 60,613.3
      and 8,262.7, and duration of hospital stay was 10.7 and 11.8 days in private and
      public hospitals respectively. More than half (55%) of the patients from middle
      class were treated in private hospitals. Of them, 278 (74.0%) were funded by
      themselves, 48 (12.8%) by loan with interest rate of 100% to 180%, 23 (6.1%) by
      loan without interest, 17 (4.5%) by losing their fixed asset, and 4 (1.1%) by
      begging in the street. Most of the patients did bear expenditure by themselves,
      followed by loan with high interest rate. 'Distress' selling of property was also
      a source. Middle-class patients could be comfortable with expenditure if they
      were in public hospitals. 

PMID- 25395910
TI  - New politics, an opportunity for maternal health advancement in eastern myanmar:
      an integrative review.
AB  - Myanmar (formerly Burma) is a southeast Asian country, with a long history of
      military dictatorship, human rights violations, and poor health indicators. The
      health situation is particularly dire among pregnant women in the ethnic
      minorities of the eastern provinces (Kachin, Shan, Mon, Karen and Karenni
      regions). This integrative review investigates the current status of maternal
      mortality in eastern Myanmar in the context of armed conflict between various
      separatist groups and the military regime. The review examines the underlying
      factors contributing to high maternal mortality in eastern Myanmar and assesses
      gaps in the existing research, suggesting areas for further research and policy
      response. Uncovered were a number of underlying factors uniquely contributing to
      maternal mortality in eastern Myanmar. These could be grouped into the following
      analytical themes: ongoing conflict, health system deficits, and political and
      socioeconomic influences. Abortion was interestingly not identified as an
      important contributor to maternal mortality. Recent political liberalization may
      provide space to act upon identified roles and opportunities for the Myanmar
      Government, the international community, and non-governmental organizations
      (NGOs) in a manner that positively impacts on maternal healthcare in the eastern
      regions of Myanmar. This review makes a number of recommendations to this effect.

PMID- 25395911
TI  - Maternal obesity and energy intake as risk factors of pregnancy-induced
      hypertension among Iranian women.
AB  - Pregnancy-induced hypertension is causing striking maternal, foetal and neonatal
      mortality and morbidity in the world. A case-control study was conducted on 113
      women with gestational hypertension and 150 healthy pregnant women at Shahid
      Akbarabadi Hospital of obstetrics and gynaecology in south of Tehran. Women who
      were obese (OR 4.44; 95% CI 1.84-10.72) before pregnancy were more likely to
      develop gestational hypertension. Proportion of having excessive gestational
      weight gain was positively and significantly associated with development of
      gestational hypertension (OR 2.70; 95% CI 1.19-6.13). Furthermore, findings
      revealed that women who were in the highest quartile of mid-arm-circumference had
      a 3-fold increased risk of gestational hypertension compared to women in the
      lowest quartile (OR 8.93; 95% CI 2.16-36.93). We found that having been in the
      highest quartile of energy intake positively correlated with increased risk of
      gestational hypertension (OR 9.66; 95% CI 3.30-28.21). The results suggest pre
      pregnancy obesity, excessive gestational weight gain, and increased intake of
      energy as potential risk factors of developing gestational hypertension. 

PMID- 25395912
TI  - Urban-rural differences in atherogenic dyslipidaemia (URDAD Study): a
      retrospective report on diabetic and non-diabetic subjects of Northern India.
AB  - Diabetes and urbanization are major contributors to increased risk factors of
      cardiovascular diseases. Studying whether atherogenic dyslipidaemia increases
      with urbanization in type 2 diabetes mellitus is, therefore, important. The
      sample of the present study consisted of 400 subjects. They were categorized
      according to residential area and diabetes into four groups: urban diabetic
      group, urban non-diabetic control group (from a metropolitan city Delhi), rural
      non-diabetic diabetic group, and rural control group (from villages of Khanpur
      Kalan, Sonepat, Haryana). Differences in lipid levels and risk factors of
      emerging cardiovascular diseases between groups were evaluated with analysis of
      variance. Diabetic patients of both urban and rural areas had significantly
      higher total cholesterol (TC), triglycerides (TG), very low-density lipoproteins
      (VLDL), TC to high-density lipoprotein cholesterol (TC/HDL) ratio, TG to high
      density lipoprotein cholesterol (TG/HDL) ratio, and atherogenic index (AI)
      compared to respective controls (p<0.05). The HDL concentrations in urban
      diabetics were significantly lower (p<0.05) than in urban non-diabetic group and
      rural diabetic group. Comparison between urban and rural diabetic groups showed
      significantly higher atherogenic dyslipidaemia (AD) in the urban patient-group
      (p<0.05). We evaluated significant relationships of diabetes and urbanization
      with AD by multiple regression analysis. Receiver operating curve (ROC) analysis
      showed high area under curve (AUC) for TG/HDL in urban diabetic group (0.776,
      p<0.0001) and in rural diabetic group (0.692, p<0.0001). It is concluded that
      diabetes was associated with higher AD parameters. Urbanization in diabetes is
      also associated with elevated levels of AD, indicating higher risk in urban
      population. This study suggests that TG/HDL may be particularly useful as
      atherogenic risk predictor in newly-diagnosed type 2 diabetic patients. 

PMID- 25395913
TI  - Recognition of and Response to neonatal intrapartum-related complications in home
      birth settings in Bangladesh.
AB  - Intrapartum-related complications (previously called 'birth asphyxia') are a
      significant contributor to deaths of newborns in Bangladesh. This study describes
      some of the perceived signs, causes, and treatments for this condition as
      described by new mothers, female relatives, traditional birth attendants, and
      village doctors in three sites in Bangladesh. Informants were asked to name
      characteristics of a healthy newborn and a newborn with difficulty in breathing
      at birth and about the perceived causes, consequences, and treatments for
      breathing difficulties. Across all three sites 'no movement' and 'no cry' were
      identified as signs of breathing difficulties while 'prolonged labour' was the
      most commonly-mentioned cause. Informants described a variety of treatments for
      difficulty in breathing at birth, including biomedical and, less often, spiritual
      and traditional practices. This study identified the areas that need to be
      addressed through behaviour change interventions to improve recognition of and
      response to intrapartum-related complications in Bangladesh. 

PMID- 25395914
TI  - Evaluation of the prevalence and correlated factors for decreased bone mass
      density among pre- and post-menopausal educated working women in Saudi Arabia.
AB  - Most of the previous studies on osteoporosis have focused on post-menopausal
      women, and more research is needed to evaluate its prevalence in pre-menopausal
      women. This study was carried out to evaluate the prevalence and correlated
      factors for decreased bone mass density among pre- and post-menopausal women.
      This was a cross-sectional study carried out in Applied Medical Sciences College
      under King Saud University. All pre- and post-menopausal women working there were
      invited to participate in the study. Measurement of bone mass density was done by
      quantitative ultrasound densitometry. One-fourth of the pre-menopausal females
      had osteopaenia. There was a significant correlation between having osteoporosis
      and increasing age, fertility period, parity, menopausal duration, gynaecological
      age, and presence of co-morbidity, especially hypertension and diabetes mellitus.
      Pre-menopausal females had high prevalence of osteopaenia (24.8%), and it is
      recommended to implement health education campaigns demonstrating the preventive
      measures of osteoporosis. 

PMID- 25395915
TI  - Determinants of the knowledge of and attitude towards tuberculosis in Nigeria.
AB  - Globally, Nigeria had the fourth highest incidence of tuberculosis (TB) cases in
      2009. Datasets of the 2008 Nigeria Demographic and Health Survey (NDHS) were used
      for examining factors associated with respondents' knowledge of and attitude
      towards TB in Nigeria. With the same age-group of males and females, the sample
      included 47,193 respondents aged 15-49 years. Factors associated with the
      knowledge of and attitude towards TB were examined against a set of individual-,
      household- and community-level variables, using multiple binary logistic
      regression analyses. Respondents who reported having ever heard of TB was 74.7%.
      Of those who ever heard of TB, 76.9% believed that TB can be cured, and 19.6%
      would want a family member's TB to be kept secret. Of those who ever heard of TB,
      63.1% believed that TB was spread from person to person through the air by
      coughing or sneezing. Multivariate analysis indicated that the probability of
      having poor knowledge of and negative attitude towards TB was consistently
      significant among the poorest household (lowest wealth quintile), geopolitical
      regions (North Central), respondents with no schooling, non-working respondents,
      youngest age-group (15-19 years), and rural areas [adjusted odds ratios
      (AOR)=0.76, 95% CI 0.66-0.86 for respondents who had ever heard of TB; AOR=0.89,
      95% CI 0.80-0.99 for respondents who had ever heard of TB and believed that TB
      can be cured; AOR=0.83, 95% CI 0.73-0.94 for those who had ever heard of TB and
      concealed the fact that a family member had TB; and AOR=0.88, 95% CI 0.78-0.99
      for those who had ever heard of TB and believed TB was spread from person to
      person through the air by coughing or sneezing]. Efforts to improve the knowledge
      of and attitude towards TB in Nigeria should focus on the youngest age-group (15
      19 years), the poorest households, and respondents with no schooling. Improving
      the knowledge and attitude of these groups of individuals may result in an
      increase in the number of people who will seek early treatment. 

PMID- 25395916
TI  - Estimating costs associated with a community outbreak of meningococcal disease in
      a colombian Caribbean city.
AB  - Meningococcal disease is a serious and potentially life-threatening infection
      that is caused by the bacterium Neisseria meningitidis (N. meningitidis), and it
      can cause meningitis, meningococcaemia outbreaks and epidemics. The disease is
      fatal in 9-12% of cases and with a death rate of up to 40% among patients with
      meningococcaemia. The objective of this study was to estimate the costs of a
      meningococcal outbreak that occurred in a Caribbean city of Colombia. We
      contacted experts involved in the outbreak and asked them specific questions
      about the diagnosis and treatment for meningococcal cases during the outbreak.
      Estimates of costs of the outbreak were also based on extensive review of medical
      records available during the outbreak. The costs associated with the outbreak
      were divided into the cost of the disease response phase and the cost of the
      disease surveillance phase. The costs associated with the outbreak control and
      surveillance were expressed in US$ (2011) as cost per 1,000 inhabitants. The
      average age of patients was 4.6 years (SD 3.5); 50% of the cases died; 50% of the
      cases were reported to have meningitis (3/6); 33% were diagnosed with
      meningococcaemia and myocarditis (2/6); 50% of the cases had bacteraemia (3/6);
      66% of the cases had a culture specimen positive for Neisseria meningitidis; 5 of
      the 6 cases had RT-PCR positive for N. meningitidis. All N. meningitidis were
      serogroup B; 50 doses of ceftriaxone were administered as prophylaxis. Vaccine
      was not available at the time. The costs associated with control of the outbreak
      were estimated at US$ 0.8 per 1,000 inhabitants, disease surveillance at US$ 4.1
      per 1,000 inhabitants, and healthcare costs at US$ 5.1 per 1,000 inhabitants. The
      costs associated with meningococcal outbreaks are substantial, and the outbreaks
      should be prevented. The mass chemoprophylaxis implemented helped control the
      outbreak. 

PMID- 25395917
TI  - Gender and Social Pressure to Change Drinking Behavior: Results from the National
      Alcohol Surveys from 1984-2010.
AB  - OBJECTIVE: Research shows social and institutional pressure influences drinking,
      yet determinants of who receives pressure are understudied. This paper examines
      age, time period, and birth cohort (APC) effects on pressure to stop or reduce
      drinking among U.S. men and women. METHODS: Data were drawn from six National
      Alcohol Surveys (NAS) conducted from 1984 to 2010 (N=32,534). Receipt of pressure
      during the past year to quit or change drinking from formal (police, doctor,
      work) and informal (spouse, family, friends) sources was assessed. RESULTS:
      Determinants of pressure were similar for men and women but varied in strength.
      They included younger age, less education, and younger cohort groups. Cohort
      effects were stronger for women than men. CONCLUSIONS: Cohort effects among women
      may be due to increased alcohol marketing to younger women and the changing
      social contexts of their drinking. Future studies should assess associations
      between drinking contexts, pressures, and outcomes.

PMID- 25395918
TI  - IPM thresholds for Agriotes wireworm species in maize in Southern Europe.
AB  - Currently, integrated pest management (IPM) of wireworms is not widespread in
      Europe. Therefore, to estimate the densities of three major wireworm species in
      southern Europe (Agriotes brevis Candeze, A. sordidus Illiger, and A. ustulatus
      Schaller), bait traps were deployed pre-seeding in maize fields in north-eastern
      Italy between 1993 and 2011. Research discovered that there was a significant
      correlation between all three wireworm species caught in the bait traps and
      damage to maize plants, but damage symptoms varied. Wherever A. ustulatus was the
      main species caught, there was no significant damage to maize plants, but seeds
      were damaged. Most of the symptoms caused by A. brevis and A. sordidus were to
      the central leaf/leaves, which wilted because of feeding on the collar. A. brevis
      was the most harmful species; when more than one A. brevis wireworm was caught
      per trap, plant damage sometimes resulted in reduced yield. Five A. ustulatus
      larvae per trap caused the same damage to maize as one A. brevis. A. sordidus
      came second (threshold two larvae/trap). These thresholds are reliable for: (1)
      bare soil in which there are no alternative food sources; (2) average soil
      temperature 10 cm beneath the surface of above 8  degrees C for 10 days; (3) soil
      humidity near to field water capacity, but days of flooding have not been
      considered. The implementation of the practical method described herein may lead
      to effective IPM of wireworms in maize and to a significant reduction in the
      number of fields treated with soil insecticides.

PMID- 25395919
TI  - Triarylphosphine Ligands with Hemilabile Alkoxy Groups. Ligands for Nickel(II)
      Catalyzed Olefin Dimerization Reactions. Hydrovinylation of Vi-nylarenes, 1,3
      Dienes, and Cycloisomerization of 1,6-Dienes.
AB  - Substitution of one of the phenyl groups of triphenylphosphine with a 2-benzyloxy
      , 2-benzyloxymethyl- or 2-benzyloxyethyl-phenyl moiety results in a set of simple
      ligands, which exhibit strikingly different behaviour in various nickel(II)
      catalyzed olefin dimerization reactions. Complexes of ligands with 2
      benzyloxyphenyl-, 2-benzyloxymethylphenyl-diphenylphosphine (L5 and L6
      respectively) are most active for hydrovinylation (HV) of vinylarenes, with the
      former leading to extensive isomerization of the primary 3-aryl-1-butenes into
      the conjugated 2-aryl-2-butenes even at -55  degrees C. However, 2
      benzyloxymethyl-substituted ligand L6 is slightly less active, leading up to
      quantitative yields of the primary products of HV at ambient temperature with no
      trace of isomerization, thus providing the best option for a practical synthesis
      of these compounds. In sharp contrast, hydrovinylation of a variety of 1,3-dienes
      is best catalyzed by nickel(II)-complexes of 2-benzyloxyphenyldiphenylphosphine,
      L5. The other two ligands, 2-benzyloxymethyl-(L6) and 2-benzyloxyethyl
      diphenylphosphine (L7) are much less effective in the HV of 1,3-dienes.
      Nickel(II)-catalyzed cycloisomerization of 1,6-dienes into
      methylenecyclopentanes, a reaction mechanistically related to the other
      hydrovinylation reactions, is also uniquely effected by nickel(II)-complexes of
      L5, but not of L6 or L7. In an attempt to prepare authentic samples of the
      methylencyclohexane products, nickel(II)-complexes of N-heterocyclic carbene
      ligands were examined. In sharp contrast to the phosphines, which give the
      methylenecyclopentanes, methylenecyclohexanes are the major products in the (N
      heterocyclic carbene)nickel(II)-mediated reactions.

PMID- 25395920
TI  - Arrayed Hollow Channels in Silk-based Scaffolds Provide Functional Outcomes for
      Engineering Critically-sized Tissue Constructs.
AB  - In the field of regenerative medicine there is a need for scaffolds that support
      large, critically-sized tissue formation. Major limitations in reaching this goal
      are the delivery of oxygen and nutrients throughout the bulk of the engineered
      tissue as well as host tissue integration and vascularization upon implantation.
      To address these limitations we previously reported the development of a porous
      scaffold platform made from biodegradable silk protein that contains an array of
      vascular-like structures that extend through the bulk of the scaffold. Here we
      report that the hollow channels play a pivotal role in enhancing cell
      infiltration, delivering oxygen and nutrients to the scaffold bulk, and promoting
      in vivo host tissue integration and vascularization. The unique features of this
      protein biomaterial system, including the vascular structures and tunable
      material properties, render this scaffold a robust and versatile tool for
      implementation in a variety of tissue engineering, regenerative medicine and
      disease modeling applications.

PMID- 25395921
TI  - Highly tunable elastomeric silk biomaterials.
AB  - Elastomeric, fully degradable and biocompatible biomaterials are rare, with
      current options presenting significant limitations in terms of ease of
      functionalization and tunable mechanical and degradation properties. We report a
      new method for covalently crosslinking tyrosine residues in silk proteins, via
      horseradish peroxidase and hydrogen peroxide, to generate highly elastic
      hydrogels with tunable properties. The tunable mechanical properties, gelation
      kinetics and swelling properties of these new protein polymers, in addition to
      their ability to withstand shear strains on the order of 100%, compressive
      strains greater than 70% and display stiffness between 200 - 10,000 Pa, covering
      a significant portion of the properties of native soft tissues. Molecular weight
      and solvent composition allowed control of material mechanical properties over
      several orders of magnitude while maintaining high resilience and resistance to
      fatigue. Encapsulation of human bone marrow derived mesenchymal stem cells (hMSC)
      showed long term survival and exhibited cell-matrix interactions reflective of
      both silk concentration and gelation conditions. Further biocompatibility of
      these materials were demonstrated with in vivo evaluation. These new protein
      based elastomeric and degradable hydrogels represent an exciting new biomaterials
      option, with a unique combination of properties, for tissue engineering and
      regenerative medicine.

PMID- 25395922
TI  - Nanoparticles with Precise Ratiometric Co-Loading and Co-Delivery of Gemcitabine
      Monophosphate and Cisplatin for Treatment of Bladder Cancer.
AB  - Combination chemotherapy is a common practice in clinical management of
      malignancy. Synergistic therapeutic outcome is only achieved when tumor cells are
      exposed to cells in an optimal ratio. However, due to diverse physicochemical
      properties of drugs, no free drug cocktails or nanomaterials are capable of co
      loading and co-delivering drugs at an optimal ratio. Herein, we develop a novel
      nano-platform with precise ratiometric co-loading and co-delivery of two
      hydrophilic drugs for synergistic anti-tumor effects. Based on previous work, we
      utilize a solvent displacement method to ratiometrically load dioleoyl
      phosphatidic acid (DOPA)-gemcitabine monophosphate and DOPA coated cisplatin
      precipitate nanocores into the same PLGA NP. These cores are designed to have
      similar hydrophobic surface properties. GMP and cisplatin are engineered into
      PLGA NP at an optimal synergistic ratio (5:1, mol:mol) with over 70%
      encapsulation efficiency and were ratiometrically taken up by tumor cells in
      vitro and in vivo. These PLGA NP exhibit synergistic anti-cancer effects in a
      stroma-rich bladder tumor model. A single injection of dual drugs in PLGA NP can
      significantly inhibit tumor growth. This nanomaterial-system solves problems
      related to ratiometric co-loading and co-delivery of different hydrophilic
      moieties and provides possibilities for co-loading hydrophilic drugs with
      hydrophobic drugs for combination therapy.

PMID- 25395923
TI  - The influence of corticosteroid treatment on the OPG/RANK/RANKL pathway and
      osteocalcin in patients with pemphigus.
AB  - INTRODUCTION: Pemphigus is a rare autoimmune blistering disease, which requires
      prolonged administration of corticosteroids at high doses. Although this therapy
      improves the health and lives of patients, it may have various side effects, for
      example osteoporosis. AIM: To assess the concentration of osteoprotegerin (OPG),
      the soluble receptor activator of nuclear factor-kappabeta ligand (sRANKL) and
      osteocalcin in patients with pemphigus. MATERIAL AND METHODS: The study comprised
      a group of 29 patients with pemphigus (17 women and 12 men) aged between 23 years
      and 75 years treated from 1994 to 2009 in the Department of Dermatology and
      Venereology, Medical University of Lodz, as well as 24 healthy volunteers matched
      appropriately in terms of gender and age. RESULTS: In patients with pemphigus,
      the mean osteoprotegerin concentration was up to 16.46% higher than in the
      control group. The average RANKL concentration in serum of patients with
      pemphigus was 26.88% higher. However, the patient group demonstrated a
      significantly lower concentration of osteocalcin by up to 18.03%. CONCLUSIONS:
      Under corticosteroid treatment, RANKL, which is released by osteoblasts, links
      with the RANK specific osteoclast receptor and stimulates osteoclastogenesis.
      This reaction can be blocked by osteoprotegerin, which is a competitive inhibitor
      to the same receptor site. A decreased osteoblast activity stimulates bone loss.
      The reduced level of osteocalcin, which is regarded as a marker for bone
      formation, and a simultaneously elevated RANK level reveal the promotion of
      osteoclast proliferation in patients treated with corticosteroids.

PMID- 25395924
TI  - Apprehension of the disease by patients suffering from psoriasis.
AB  - INTRODUCTION: Psoriasis affects about 1-2% of the entire population. Due to its
      chronicity and relapsing course, psoriasis has a great influence on patients'
      quality of life and psychological status. AIM: To evaluate apprehensaion of the
      disease by psoriatic patients. MATERIAL AND METHODS: One hundred psoriasis
      patients (36 females, 64 males; mean age 47.3 +/-15.8 years) were enrolled. Mean
      psoriasis severity assessed according to PASI was 17.1 +/-10.0 points. Each
      participant underwent a careful physical examination and completed a specially
      designed questionnaire containing questions about perception of psoriasis
      severity, disease aggravating factors, most bothersome symptoms, possible causes
      of psoriasis and treatment efficacy. RESULTS: A correlation between patients'
      psoriasis assessment and objective measurement of disease intensity by PASI was
      weak, albeit significant (rho = 0.37, p < 0.001). A total of 49% of patients
      indicated that psoriasis had an enormous negative impact on their life and 40%
      declared that psoriasis decreased their self-esteem. Patients with decreased self
      esteem were significantly younger and more frequently employed. A marked portion
      of patients believed that their disease will be cured in the future. Patients
      expecting a rapid cure of disease had experienced a later disease onset and
      suffered from psoriasis significantly shorter. The most burdensome symptoms of
      psoriasis were intense epidermal scaling (66% of responders), itching (65%), skin
      redness (51%), burning (44%), dandruff (38%), and nail abnormalities (37%).
      CONCLUSIONS: Psoriasis may negatively affect patients' everyday life, but the
      degree of that influence and the level of psoriasis understanding depend on
      various clinical parameters as well as on demographic characteristics.

PMID- 25395925
TI  - Triggering drug use in patients with psoriasis: an investigative report from
      Turkey.
AB  - INTRODUCTION: The patients clinically diagnosed with psoriasis were investigated
      for drug use that may trigger psoriasis. AIM: To minimize the triggering drug use
      and help the medical treatment of psoriasis patients. MATERIAL AND METHODS: The
      study involved 289 psoriatic patients who attended our clinic in 2010-2012 and
      were asked to bring their drug lists of the last year, which they obtained from
      the pharmacy's record system. They were advised not to use the drugs that may
      trigger psoriasis. Data analyses were performed using SPSS program version 19.0.
      RESULTS: A total of 289 patients were included in the study. Two hundred and
      twenty-one patients were using non-steroidal anti-inflammatory drugs; 133
      patients were using anti-reflux drugs; 35 patients were using antidiabetic drugs;
      31 patients were using calcium-channel blockers and 24 patients were using beta
      blockers. In our study group, there was no significantly difference between
      median PASI scores of the patients using a triggering drug and those of who are
      not using a triggering drug. However, there was a positive low correlation
      between PASI rates and numbers of drugs used (r = 0.180, p = 0.013). CONCLUSIONS:
      Many other factors may trigger psoriasis, therefore the effect of stopping or
      minimizing the drug use on disease remission is not known. Because of the high
      triggering drug use rate, it is important to enlighten psoriasis patients about
      triggering drugs.

PMID- 25395926
TI  - Itch, disease coping strategies and quality of life in psoriasis patients.
AB  - INTRODUCTION: Psoriasis is a psychodermatological condition, so psychological
      factors can trigger and/or exacerbate skin lesions. Additionally, disease can be
      a source of stress and can worsen patients' quality of life (QoL). AIM: To
      evaluate the relationship between medical (disease severity, itch) and
      psychological variables (disease coping strategies, QoL) in the psoriasis
      patients group. MATERIAL AND METHODS: The study comprises 60 in-patients of the
      dermatological ward (30 females and 30 males) with the diagnosis of psoriasis.
      METHODS USED: Psoriasis Area and Severity Index (PASI), Itch Severity Evaluation
      Questionnaire, Coping with Skin Disease Scale-SRS-DER, SKINDEX-29 questionnaire.
      RESULTS: The study demonstrated significant correlations between disease coping
      strategies, itch and quality of life. Women presented worse QoL (generally and in
      physical functioning). The older patients with a longer disease duration revealed
      QoL impairment. CONCLUSIONS: The obtained results could help in identifying
      patients risk groups which are in the highest danger of decreased QoL. Our data
      indicate the need for psychological interventions.

PMID- 25395927
TI  - Changes in blood eosinophilia during omalizumab therapy as a predictor of asthma
      exacerbation.
AB  - INTRODUCTION: Omalizumab is a monoclonal anti-immunoglobulin E antibody developed
      for the treatment of severe allergic asthma. The number of exacerbations used as
      a parameter of omalizumab therapy efficacy may be insufficient in many cases due
      to a relatively short time to first evaluation (16 weeks). Therefore, it is
      advisable to look for parameters of more prognostic value while continuing
      omalizumab therapy. AIM: To evaluate usefulness of analysis of changes of blood
      eosinophilia after 16 weeks of omalizumab therapy as a predictor of asthma
      exacerbations. MATERIAL AND METHODS: The study was conducted on a group of 13
      patients with severe persistent allergic asthma treated with omalizumab. Blood
      eosinophil counts were measured before and after 16 weeks of anti-IgE therapy. On
      the basis of percentage of eosinophilia decrease (> 50% or < 50% of the initial
      value), patients were divided into two groups. Analysis of the asthma
      exacerbation rate during 12 months and time to first exacerbation was performed.
      RESULTS: In the group with a high decrease in blood eosinophil counts (group 1)
      we showed a statistically significantly lower asthma exacerbation rate in 12
      months compared with the group with a low decrease in blood eosinophil counts
      (group 2) (p = 0.02). We also observed the tendency to longer time to first
      asthma exacerbation in group 1 compared to group 2 (p = 0.06). CONCLUSIONS: Our
      results showed that a decrease in blood eosinophilia during omalizumab therapy
      can be a predictor of asthma exacerbation. Evaluation of changes in blood
      eosinophil count should be taken into the consideration while estimating response
      to anti-IgE therapy in patients with severe allergic asthma.

PMID- 25395929
TI  - Eosinophilic cellulitis (Wells' syndrome) caused by a temporary henna tattoo.
AB  - Eosinophilic cellulitis (Wells' syndrome) is an uncommon condition of unknown
      etiology. Wells' syndrome is usually seen in adulthood but very rare in
      childhood. Although pathogenesis of the disease is not very clear, it is a
      hypersensitivity reaction developing against a variety of exogenous and
      endogenous antigenic stimuli. Paraphenylenediamine is a strong allergen
      frequently used as a temporary henna tattoo, which makes the color darker. Here,
      a 9-year-old male patient with Wells' syndrome is presented, which developed
      following a temporary henna tattoo and shown by the patch test sensitivity to
      paraphenylenediamine. 

PMID- 25395928
TI  - Chromoblastomycosis.
AB  - Chromoblastomycosis is a chronic fungal infection of the skin and subcutaneous
      tissue. The infection usually results from a traumatic injury and inoculation of
      microorganism from a specific group of dematiaceous fungi (usually Fonsecaea
      pedrosoi, Phialophora verrucosa, Cladophialophora carrionii). In the tissues
      fungi produce characteristic sclerotic cells or muriform cells. Dermal lesions
      can range from small nodules to large papillary-like eruptions. The disease has
      been described worldwide but the prevalence is higher in rural populations in
      countries with a tropical or subtropical climate, such as Madagascar in Africa
      and Brazil in South America. Diagnostic techniques are based on direct
      examination, culture and histopathology. Despite a variety of treatment
      modalities, which include long courses of antifungals, surgical excision and
      destructive physical therapies, the disease remains one of the most difficult
      deep mycotic infections to eradicate. 

PMID- 25395930
TI  - Merkel cell carcinoma: an illustrative case and review.

PMID- 25395931
TI  - Half-and-half nail in a case of isoniazid-induced pellagra.

PMID- 25395932
TI  - Long-term treatment of refractory severe chronic urticaria by omalizumab:
      analysis of two cases.

PMID- 25395933
TI  - Confluent and reticulated papillomatosis manifested as vertically rippled and
      keratotic plaques.

PMID- 25395934
TI  - Severe Darier's disease patient with mutation of ATP2A2.

PMID- 25395935
TI  - The incidence of acute myocardial infarction in relation to overweight and
      obesity: a meta-analysis.
AB  - INTRODUCTION: Epidemiological evidence suggests that overweight and obesity have
      been associated with acute myocardial infarction (AMI). However, data on this
      issue are controversial. This study aims to use meta-analysis to determine
      whether overweight and obesity are related to AMI. MATERIAL AND METHODS: We
      searched PubMed and Embase databases up to October 23(rd), 2013 for related
      literature. The association of overweight and obesity with AMI was assessed by
      odd ratio (OR) with 95% confidence interval (CI) as the effect size. Then
      subgroup analysis was performed according to gender, area and study type.
      RESULTS: Five primary studies (one cohort study and four case-control studies)
      were included in this meta-analysis involving 36 803 participants, 14 883 of whom
      had an AMI. There was a significant association between overweight and AMI (OR =
      1.27, 95% CI: 1.21-1.33, p < 0.001). Similar results revealed a relation between
      obesity and AMI (OR = 1.22, 95% CI: 1.07-1.40, p = 0.003). Subgroup analysis
      showed that overweight and obesity were positively associated with AMI risk
      except for obese subjects in Europe. There was no publication bias (Begg's test p
      = 0.972, Egger's test p = 0.858). CONCLUSIONS: Both overweight and obesity
      increased the incidence of AMI, and it is necessary to control weight to prevent
      AMI. A large number of studies is needed to explore the mechanisms that link
      overweight and obesity with AMI.

PMID- 25395936
TI  - Prognostic role of SPARC expression in gastric cancer: a meta-analysis.
AB  - INTRODUCTION: Secreted protein acidic and rich in cysteine (SPARC) is involved in
      regulating cell adhesion, proliferation, migration, and tissue remodeling. We
      performed a meta-analysis to evaluate the association between SPARC expression
      and the clinicopathologic features and outcomes of gastric cancer patients.
      MATERIAL AND METHODS: Publications that assessed the clinical or prognostic
      significance of SPARC in gastric cancer up to October 2013 were identified. A
      meta-analysis was performed to clarify the association between SPARC expression
      and clinical outcomes. RESULTS: Ten studies, including 1417 cases, met the
      inclusion criteria. The data were analyzed and the results show that SPARC is not
      significantly associated with the depth of gastric cancer invasion (odds ratio
      (OR) = 1.17, 95% confidence interval (CI): 0.60-2.29, Z = 0.47, p = 0.64) or
      tumor differentiation (OR = 0.59, 95% CI: 0.22-1.58, Z = 1.06, p = 0.29).
      Moreover, SPARC was not significantly correlated with lymph node metastasis (OR =
      0.72, 95% CI: 0.37-1.41, Z = 0.96, p = 0.34). However, SPARC overexpression was
      highly correlated with reduced overall survival (relative risk (RR) = 1.78, 95%
      CI: 1.52-2.09, Z = 7.10, p = 0.43). CONCLUSIONS: The SPARC may play an important
      role in the progression of gastric cancer, and SPARC overexpression is closely
      correlated with poor patient survival. The SPARC is a potential clinical marker
      for the survival of gastric cancer patients; however, well-designed prospective
      studies are needed to confirm these findings.

PMID- 25395937
TI  - Carotid intima media thickness and low high-density lipoprotein (HDL) in South
      Asian immigrants: could dysfunctional HDL be the missing link?
AB  - INTRODUCTION: South Asian immigrants (SAIs) in the US exhibit higher prevalence
      of coronary artery disease (CAD) and its risk factors compared with other ethnic
      populations. Conventional CAD risk factors do not explain the excess CAD risk;
      therefore there is a need to identify other markers that can predict future risk
      of CAD in high-risk SAIs. The objective of the current study is to assess the
      presence of sub-clinical CAD using common carotid artery intima-media thickness
      (CCA-IMT), and its association with metabolic syndrome (MS) and pro
      inflammatory/dysfunctional HDL (Dys-HDL). MATERIAL AND METHODS: A community-based
      study was conducted on 130 first generation SAIs aged 35-65 years. Dys-HDL was
      determined using the HDL inflammatory index. Analysis was completed using
      logistic regression and Fisher's exact test. RESULTS: Sub-clinical CAD using CCA
      IMT >= 0.8 mm (as a surrogate marker) was seen in 31.46%. Age and gender adjusted
      CCA-IMT was significantly associated with type 2 diabetes (p = 0.008),
      hypertension (p = 0.012), high-sensitivity C-reactive protein (p < 0.001) and
      homocysteine (p = 0.051). Both the presence of MS and Dys-HDL was significantly
      correlated with CCA-IMT, even after age and gender adjustment. The odds of having
      Dys-HDL with CCA-IMT were 5 times (95% CI: 1.68, 10.78). CONCLUSIONS: There is a
      need to explore and understand non-traditional CAD risk factors with a special
      focus on Dys-HDL, knowing that SAIs have low HDL levels. This information will
      not only help to stratify high-risk asymptomatic SAI groups, but will also be
      useful from a disease management point of view.

PMID- 25395938
TI  - Obesity risk factors in a representative group of Polish prepubertal children.
AB  - INTRODUCTION: The study aim was to evaluate risk factors of obesity in Polish
      children aged 7 to 9 years. MATERIAL AND METHODS: A representative group of 2571
      children (1268 girls and 1303 boys) was randomly selected according to the
      European Childhood Obesity Group protocol. Weight and height were measured and
      body mass index (BMI) was calculated. A questionnaire was completed by the
      children's parents with respect to behavioural and family-related risk factors of
      obesity. International Obesity Task Force criteria were used for classification
      of children's obesity. RESULTS: Obesity was found in 3.7% of girls and 3.6% of
      boys. There was a statistically significant association between the prevalence of
      obesity in girls and their mother's obesity: OR = 5.06 (1.96-13.05), p < 0.001,
      father's obesity: OR = 5.19 (1.96-13.69), p < 0.001, and both parents' obesity:
      OR = 5.43 (1.39-21.29), p = 0.01. Obesity in boys was significantly associated
      with mother's obesity: OR = 5.6 (2.6-12.02), p < 0.001, father's obesity: OR =
      6.21 (2.89-13.37), p < 0.001, and both parents' obesity: OR = 7.22 (2.44-31.33),
      p < 0.001. Skipping or irregular eating of breakfast was a risk factor for
      obesity in girls with OR = 2.71 (1.33-5.51), p = 0.005. Neither family income nor
      parents' education level was related to their offspring's obesity. TV watching,
      physical activity level and eating in fast food places were not significant risk
      factors for obesity. CONCLUSIONS: Eating breakfast regularly seems to protect
      girls from obesity development while low physical activity is not a significant
      obesity risk factor in this age group for either boys or girls. This finding
      stresses the more important role of healthy diet than physical activity promotion
      in obesity prevention in prepubertal children.

PMID- 25395939
TI  - Peripheral blood lymphocyte subsets (CD4+, CD8+ T cells), leptin level and weight
      loss after laparoscopic greater curvature plication in morbidly obese patients.
AB  - INTRODUCTION: The aim of the study was to detect the effect of laparoscopic
      greater curvature plication (LGCP) on peripheral blood lymphocyte subsets (helper
      and cytotoxic T lymphocytes - CD4+ and CD8+ T cells respectively), leptin level
      and weight loss in morbidly obese patients. MATERIAL AND METHODS: Morbidly obese
      patients (n = 20, age range: 25-50 years, body mass index (BMI) range: 37-45
      kg/m(2)) who underwent LGCP were enrolled in a prospective study to determine the
      percentages of their peripheral blood T cells (CD4+ and CD8+) before and 4 months
      postoperatively using flow cytometry. Also, the level of their leptin before and
      4 months postoperatively was established using enzyme-linked immunosorbent assay
      (ELISA). The data are expressed as the percentage of total lymphocytes +/- the
      standard error of the mean. RESULTS: A decrease in the BMI and loss of weight
      (31.20 +/-1.2%) were confirmed 4 months postoperatively since BMI was 44.71 +/
      4.3 (range: 37-45) kg/m(2) preoperatively, and decreased to 31.80 +/-1.1 (range:
      24-33) kg/m(2) after surgery. The mean percentage of CD4+ and CD8+ T lymphocytes
      significantly decreased postoperatively (38.2 +/-1.5 before and 29.3 +/-2.6 after
      operation for CD4+, 17.3 +/-1.8 preoperatively and 9.5 +/-1.7 postoperatively for
      CD8+, p < 0.05). The mean leptin level was 43.01 +/-22.01 preoperatively while
      postoperatively it was 24.8 +/-11.1 (p < 0.05), so the leptin level substantially
      decreased compared to its preoperative values. CONCLUSIONS: This study found that
      weight loss after LGCP in morbidly obese patients led to decreases in levels of
      leptin and circulating immune cells compared to their preoperative values.

PMID- 25395940
TI  - Validation of the Polish version of Diabetes Quality of Life - Brief Clinical
      Inventory (DQL-BCI) among patients with type 2 diabetes.
AB  - INTRODUCTION: The aim of the study was to develop a Polish version of the
      Diabetes Quality of Life Brief Clinical Inventory (DQL-BCI) and to perform
      validating evaluation of selected psychometric aspects. MATERIAL AND METHODS: The
      translation process was performed in accordance with generally accepted
      international principles of translation and cultural adaptation of measurement
      tools. Two hundred and seventy-four subjects with type 2 diabetes completed the
      Polish version of DQL-BCI, the generic EQ-5D questionnaire and the diabetes
      specific DSC-R. The examination provides information about the reliability
      (internal consistency, test-retest) and the construct validity of the studied
      tool (the relationship between the DQL-BCI score and EQ-5D and DSC-R scales, as
      well as selected clinical patient characteristics). RESULTS: Cronbach's alpha
      (internal consistency) for the translated version of DQL-BCI was 0.76. Test
      retest Pearson correlation coefficient was 0.96. Spearman's coefficient
      correlation between DQL-BCI score and EQ-5D index and EQ-VAS were 0.6 (p =
      0.0000001) and 0.61 (p = 0.0000001) respectively. The correlation between scores
      of the examined tool and DSC-R total score was -0.6 (p = 0.0000001). Quality of
      life was lower among patients with microvascular as well as macrovascular
      complications and with occurring hypoglycemic episodes. CONCLUSIONS: The result
      of this study is the Polish scale used to test the quality of life of patients
      with diabetes, which includes the range of problems faced by patients while
      maintaining a patient-friendly form. High reliability of the scale and good
      construct validity qualify the Polish version of DQL-BCI as a reliable tool in
      both research and individual diagnostics.

PMID- 25395941
TI  - Usefulness of patient's history and non-invasive electrocardiographic parameters
      in prediction of ajmaline test results in patients with suspected Brugada
      syndrome.
AB  - INTRODUCTION: The aim of the work was to assess the usefulness of patient's
      history and non-invasive electrocardiographic parameters in the prediction of
      ajmaline test results in patients with suspected Brugada syndrome. MATERIAL AND
      METHODS: The study involved a group of 59 patients (37 men) at average age of
      31.6 +/-12.2 years with suspected concealed form of Brugada syndrome.
      Pharmacological provocation with intravenous ajmaline administration was
      performed. The patients were divided into two groups depending on ajmaline test
      results. Individual and total predictive value for ajmaline test was based on the
      analysis of medical anamnesis and non-invasive electrocardiographic examination.
      RESULTS: The analysis carried out within the work indicated a special predictive
      value of 2 parameters which constituted the study inclusion criteria - family
      history of Brugada syndrome (28.6% vs. 3.8%; p = 0.0477) and occurrence of
      saddleback electrocardiographic changes in ECG curve (42.9% vs. 0.0%; p =
      0.0002). Non-invasive electrocardiographic parameters which showed significant
      predictive value for ajmaline test were as follows: dispersion of QTc interval
      (prior to the provocation test 54.43 +/-24.77 ms vs. 32.70 +/-12.98 ms; p =
      0.0005 and during daytime activity 46.81 +/-27.16 ms vs. 32.07 +/-13.19 ms; p =
      0.0198), corrected QT intervals, Tpeak-Tend intervals in particular leads, QTpeak
      intervals, dispersion of Tpeak-Tend interval assessed from precordial leads (V1
      V6) (42.86 +/-13.80 ms vs. 26.54 +/-11.70 ms; p = 0.001) and J-point elevation in
      V2 and V3 leads. CONCLUSIONS: Both interview and non-invasive
      electrocardiographic parameters which reflect cardiomyocyte repolarization
      disorders are of high predictive value in anticipating ajmaline pharmacological
      provocation results in patients with suspected Brugada syndrome.

PMID- 25395942
TI  - In-hospital daily insulin dose predicts long-term adverse outcome in patients
      with diabetes with ST-elevation myocardial infarction treated with successful
      primary percutaneous angioplasty.
AB  - INTRODUCTION: Early initiation of reperfusion therapy including primary
      percutaneous coronary revascularization (PPCI) has been recognized as a crucial
      factor determining clinical outcomes in the acute phase of myocardial infarction.
      In unstable patients with type 2 diabetes mellitus (T2D) the clear benefit from
      PPCI was proven. We aim to evaluate the prognostic value of factors describing
      glycometabolic state on admission in patients with T2D undergoing PPCI in acute
      ST-elevation myocardial infarction (STEMI). MATERIAL AND METHODS: Prospective
      analysis of clinical and laboratory variables (mean daily short acting exogenous
      insulin dose (DID), admission blood glucose, glycated hemoglobin (HbA1c),
      microalbuminuria) was performed in 112 consecutive patients with T2D with STEMI
      who underwent PPCI. Women comprised 58% of the group. RESULTS: Insulin dosing was
      targeted to obtain a mean daily glucose level < 7.8 mmol/l. During 12-month
      follow-up 33 (29.5%) major adverse cardiac events (major adverse cardiac events
      (MACE) consisting of death, reinfarction, and repeated target vessel
      revascularization) were reported. Microalbuminuria was present in 68 (60.5%)
      patients. The mean HbA1c level was 7.9%. In the multivariate logistic regression
      model only DID > 44 IU remained an independent risk factor for MACE (p = 0.02, OR
      = 5.2). CONCLUSIONS: In patients with diabetes with STEMI treated with PPCI,
      simple measurement of DID during hospitalization can add valuable prognostic
      information about the future risk of MACE.

PMID- 25395943
TI  - Potential drug-drug interactions in hospitalized patients with chronic heart
      failure and chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Polypharmacy is common in patients with chronic heart failure (HF)
      and/or chronic obstructive pulmonary disease (COPD), but little is known about
      the prevalence and significance of drug-drug interactions (DDIs). This study
      evaluates DDIs in hospitalized patients. MATERIAL AND METHODS: We retrospectively
      screened medical charts over a 6-month period for diagnosis of chronic HF and/or
      COPD. Potential DDIs were evaluated using Lexi-Interact software. RESULTS: Seven
      hundred and seventy-eight patients were included in the study (median age 75
      years, 61% men). The median number of drugs on admission and discharge was 6
      (interquartile range (IQR) 4-9) and 7 (IQR 5-), respectively (p = 0.10). We
      recorded 6.5 +/-5.7 potential DDIs per patient on admission and 7.2 +/-5.6 on
      discharge (p = 0.2). From admission to discharge, type-C and type-X potential
      DDIs increased (p < 0.05 for both). Type X interactions were rare (< 1%), with
      the combination of a beta-blocker and a beta2 agonist being the most common
      (64%). There were significantly more type-C and type-D potential DDIs in patients
      with chronic HF as compared to patients with COPD (p < 0.001). Patients with
      concomitant chronic HF and COPD had more type-C and type-X potential DDIs when
      compared to those with individual disease (p < 0.005). An aldosterone antagonist
      and ACE inhibitor/ARB were prescribed to 3% of chronic HF patients with estimated
      glomerular filtration rate < 30 ml/(min * 1.73 m(2)). CONCLUSIONS: The DDIs are
      common in patients with chronic HF and/or COPD, but only a few appear to be of
      clinical significance. The increase in potential DDIs from admission to discharge
      may reflect better guideline implementation rather than poor clinical practice.

PMID- 25395944
TI  - The effect of postoperative positive end-expiratory pressure on postoperative
      bleeding after off-pump coronary artery bypass grafting.
AB  - INTRODUCTION: To compare postoperative prophylactic use of two positive end
      expiratory pressure (PEEP) levels in order to prevent postoperative bleeding in
      patients undergoing off-pump coronary artery bypass grafting (CABG) surgery.
      MATERIAL AND METHODS: Sixty patients undergoing an elective off-pump CABG
      operation were included in this prospective, nonrandomized clinical trial.
      Patients were divided into two groups as receiving either 5 cm H2O (group 1) or 8
      cm H2O PEEP (group 2) after the operation until being extubated. Chest tube
      outputs, use of blood products and other fluids, postoperative hemoglobin levels,
      accumulation of pleural and pericardial fluid after the removal of chest tubes,
      and duration of hospital stay were recorded and compared. RESULTS: Low- and high
      pressure PEEP groups did not differ with regard to postoperative chest tube
      outputs, amounts of transfusions and crystalloid/colloid infusion requirements,
      or postoperative hemoglobin levels. However, low-pressure PEEP application was
      associated with significantly higher pleural (92 +/-37 ml vs. 69 +/-29 ml, p =
      0.03) and pericardial fluid (17 +/-5 ml vs. 14 +/-6 ml, p = 0.04) accumulation.
      On the other hand, high-pressure PEEP application was associated with
      significantly longer duration of hospitalization (6.25 +/-1.21 days vs. 5.25 +/
      0.91 days, p = 0.03). CONCLUSIONS: Prophylactic administration of postoperative
      PEEP levels of 8 cm H2O, although safe, does not seem to reduce chest-tube output
      or transfusion requirements in off-pump CABG when compared to the lower level of
      PEEP. Further studies with larger sample sizes are warranted to confirm the
      benefits and identify ideal levels of PEEP administration in this group of
      patients.

PMID- 25395945
TI  - Caregiving burden and its determinants in Polish caregivers of stroke survivors.
AB  - INTRODUCTION: Despite the growing body of literature on the consequences of
      providing non-professional care to stroke survivors, the determinants of
      caregiving burden are still not fully recognized. Identification of significant
      determinants can facilitate caregiver intervention programs. The aim of this
      study was to evaluate the level of burden borne by caregivers of stroke patients
      and to identify the most important determinants of burden at 6 months after
      hospitalization. MATERIAL AND METHODS: Data were collected from 150 pairs of
      stroke patients/caregivers. Caregiver burden was assessed on the Caregiver Burden
      scale (CB). Several characteristics were measured as potential predictors of the
      burden. Special attention was paid to the caregiver's sense of coherence (SOC)
      and anxiety. Regression analysis was employed to test the hypothesized
      relationships between these variables and the burden. RESULTS: Forty-seven
      percentage of the caregivers reported a substantial burden (severe or moderate).
      Caregiver SOC (p < 0.001), anxiety (p < 0.001) and the patients' functional
      status (p < 0.001) were the most important predictors of the overall burden and
      the most consistent predictors of the majority of aspects included in the CB
      scale. Caregiver health, patient's gender, time spent caregiving and social
      support were also factors related to the burden. The identified predictors
      explained 67% of the variance in the overall burden. CONCLUSIONS: Clinicians and
      other professionals should focus on the coping abilities of caregivers, their
      emotional state and the level of patients' dependency, as these are the vital and
      modifiable factors affecting caregiver burden following stroke.

PMID- 25395946
TI  - The alcohol dehydrogenase isoenzyme alcohol dehydrogenase IV as a candidate
      marker of Helicobacter pylori infection.
AB  - INTRODUCTION: Helicobacter pylori infection is associated with decreased alcohol
      dehydrogenase (ADH) activity in the gastric mucosa. The decrease in gastric ADH
      activity depends on the severity of inflammation and mucosal injury. This damage
      can be a reason of the release of enzyme from gastric mucosa and leads to the
      increase of the ADH activity in the sera of patients with H. pylori infection.
      MATERIAL AND METHODS: Serum samples were taken from 140 patients with H. pylori
      infection. Total ADH activity was measured by photometric method with p
      nitrosodimethylaniline as a substrate and ALDH activity by the fluorometric
      method with 6-methoxy-2-naphtaldehyde. For the measurement of the activity of
      class I and II isoenzymes we employed the fluorometric methods, with class
      specific fluorogenic substrates. The activity of class III ADH was measured by
      the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a
      substrate. RESULTS: The activity of ADH IV in the serum of patients with H.
      pylori infection increased about 42% (7.86 mU/l) in the comparison to the control
      level (4.52 mU/l). Total activity of ADH was 1105 mU/l in patients group and 682
      mU/l in control. The diagnostic sensitivity for ADH IV was 88%, specificity 90%,
      positive and negative predictive values were 91% and 84% respectively. Area under
      ROC curve for ADH IV was 0.84. CONCLUSIONS: Helicobacter pylori infection of
      gastric mucosa is reflected in the serum by significant increase of class IV and
      total ADH activity. The results suggest a potential role for ADH IV as a marker
      of H. pylori infection.

PMID- 25395947
TI  - Increased level of serum prostaglandin-2 in early stage of esophageal squamous
      cell carcinoma.
AB  - INTRODUCTION: Prostaglandin-2 (PGE-2), one of the products of cyclooxygenase-2
      (COX-2) induced catalysis, may play a critical role in the carcinogenesis of
      esophageal squamous cell carcinoma (ESCC). We investigated the efficacy of using
      serum PGE-2 concentration as a biomarker for this cancer type. MATERIAL AND
      METHODS: Prostaglandin-2 levels were analyzed in the serum of 65 ESCC patients
      and in 47 healthy individuals. The concentrations of cyclooxygenase-2 (COX-2)
      were measured in tumor tissues and normal tissues obtained from 31 surgically
      treated ESCC patients. RESULTS: Serum PGE-2 concentration was significantly
      higher in ESCC patients than in control patients (p = 0.004), especially in the
      early stages (I + II) of cancer (p < 0.0001). We observed significant inverse
      relationships between serum PGE-2 levels and: tumor stage, primary tumor
      progression, lymph and distant metastasis. The COX-2 concentration was
      significantly elevated in tumors as compared to normal tissues (p = 0.008). A
      significant correlation between serum PGE-2 and tumor COX-2 was observed (rho =
      0.46, p = 0.009). However, ROC analysis showed that serum PGE-2 may be a weak
      prognostic factor for ESCC. CONCLUSIONS: Our results suggest that an elevated
      concentration of serum PGE-2 in the early stages of cancer may possibly be
      associated with tumor initiation and cancer development in ESCC. The exact role
      of these findings in early detection of this highly lethal cancer requires
      further research.

PMID- 25395948
TI  - Chronic cough - assessment of treatment efficacy based on two questionnaires.
AB  - INTRODUCTION: Efficacy of chronic cough treatment is ambiguous. The aim of the
      study was to analyze chronic cough alleviation after specific treatment and the
      relationship between cough etiology and treatment efficacy. MATERIAL AND METHODS:
      A stepwise diagnostic approach was used to diagnose cough etiology in non-smoking
      adults with chronic cough. In all patients specific treatment was applied. Two
      different questionnaires - a visual analog scale and a 5-degree scale - were used
      to assess cough severity before and after 4-6 months of treatment. RESULTS: A
      significant correlation between pre-treatment and post-treatment results of both
      questionnaires was found (Spearman coefficient 0.43, p = 0.0003 and 0.73, p <
      0.0001, respectively). Baseline questionnaire analysis revealed no differences in
      cough severity between patients with different cough causes or multiple cough
      causes. Although specific treatment resulted in a significant decrease of cough
      severity in the entire group, only partial improvement was noted. According to
      the visual analogue scale, a decrease of cough severity by at least 50% was
      achieved only in 54.4% of patients (37/68). Similarly, satisfactory improvement
      was noted in only 54.4% (37/68) of patients when using the 5-point scale. There
      were three sub-groups of patients, in whom no relevant decrease of cough severity
      was observed despite treatment: patients with 1. three coexisting cough causes,
      2. non-asthmatic eosinophilic bronchitis, and 3. chronic idiopathic cough.
      CONCLUSIONS: Cough severity does not depend on its etiology. Efficacy of chronic
      cough treatment in non-smoking patients is only moderate.

PMID- 25395949
TI  - Compliance with severe sepsis bundles and its effect on patient outcomes of
      severe community-acquired pneumonia in a limited resources country.
AB  - INTRODUCTION: Validation of compliance with severe sepsis bundles is still
      needed. The purpose of this study was to determine compliance and its outcomes in
      severe community-acquired pneumonia (CAP) patients in a limited resources
      country. MATERIAL AND METHODS: A prospective cohort study of 212 severe CAP
      patients was carried out. The implementation programme was organized into two
      continuous phases. The primary outcomes were compliance and hospital mortality.
      RESULTS: Compliance with administration of antibiotics and vasopressors as well
      as plateau pressure on average < 30 cm H2O was high in both groups. In the
      bundles group, patients received more serum lactate monitoring (62.3% vs. 11.3%),
      more blood cultures (47.1% vs. 24.5%), more fluid resuscitation (63.2% vs. 26.4%)
      and volumes infused (1319.8 +/-1107.4 ml vs. 461.9 +/-799.3 ml), more inotropic
      dobutamine and/or packed red blood cells (21.7% vs. 10.0%), more low-dose
      steroids (56.5% vs. 15.0%), and more glucose control (51.9% vs. 6.6%) compared
      with such patients in the control group. The rates of total compliance with 6
      hour, 24-hour, and 6/24-hour bundles in the prospective period were 47.1%, 51.9%,
      and 42.5%, respectively. Hospital mortality was reduced from 44.3% to 29.2% (p =
      0.023) in the bundles group, and the compliant subgroup had a more than twofold
      decrease in mortality (17.8% vs. 37.7%, p = 0.003). Serum lactate measured, blood
      cultures, and fluid resuscitation showed independent relationships with decreased
      mortality. CONCLUSIONS: Total compliance was relatively low, but the
      implementation of severe sepsis bundles could clearly reduce mortality from
      severe CAP.

PMID- 25395950
TI  - The effects of botulinum toxin type A on improvement and dynamic spastic equinus
      correction in children with cerebral palsy - preliminary results.
AB  - INTRODUCTION: We evaluated the effects of botulinum toxin type A (BTA) with
      physical therapy on dynamic foot equinus correction and higher motor functional
      outcome in children with spastic type of cerebral palsy (CP). MATERIAL AND
      METHODS: Ankle joint active and passive movement, gastrocnemial muscle spasticity
      levels (Modified Ashworth Scale (MAS)), and higher motor functional status (Gross
      Motor Function Classification System (GMFCS) and Gross Motor Function Measure
      (GMFM) (GMFM-D - standing and GMFM-E - walking) were assessed before treatment
      and 3, 8, 16 weeks and 6 months after BTA administration in 12 children. RESULTS:
      There was a significant improvement of active (initial - (-)13.07 +/-5.78; 6
      months - (-)10.64 +/-4.77; p < 0.001) and passive (initial - 4.21 +/-2.29; 6
      months - 4.71 +/-2.16; p < 0.05) ankle joint foot dorsiflexion. GMFM-D and GMFM-E
      were significantly higher after 3, 8, 16 weeks (p < 0.001) and GMFM-D after 6
      months (p < 0.001). CONCLUSIONS: Botulinum toxin type A administration and
      physical therapy in patients with spastic CP improves the motion range of dynamic
      foot equinus after 3 weeks and higher motor functional outcome (standing and
      walking).

PMID- 25395951
TI  - Effects of preoperative physiotherapy in hip osteoarthritis patients awaiting
      total hip replacement.
AB  - INTRODUCTION: The World Health Organization (WHO) claimed osteoarthritis as a
      civilization-related disease. The effectiveness of preoperative physiotherapy
      among patients suffering hip osteoarthritis (OA) at the end of their conservative
      treatment is rarely described in the literature. The aim of this study was to
      assess the quality of life and musculoskeletal health status of patients who
      received preoperative physiotherapy before total hip replacement (THR) surgery
      within a year prior to admission for a scheduled THR and those who did not.
      MATERIAL AND METHODS: Forty-five patients, admitted to the Department of
      Orthopaedics and Traumatology of Locomotor System for elective total hip
      replacement surgery, were recruited for this study. The assessment consisted of a
      detailed interview using various questionnaires: the Harris Hip Score (HHS), the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the 36
      Item Short Form Health Survey (SF-36), and the Hip disability and Osteoarthritis
      Outcome Score (HOOS), as well as physical examination. Patients were assigned to
      groups based on their attendance of preoperative physiotherapy within a year
      prior to surgery. RESULTS: Among patients who received preoperative physiotherapy
      a significant improvement was found for pain, daily functioning, vitality,
      psychological health, social life, and (active and passive) internal rotation (p
      < 0.05). CONCLUSIONS: Patients are not routinely referred to physiotherapy within
      a year before total hip replacement surgery. This study confirmed that pre
      operative physiotherapy may have a positive influence on selected musculoskeletal
      system status indicators and quality of life in hip osteoarthritis patients
      awaiting surgery.

PMID- 25395952
TI  - Does concomitant meniscectomy affect medium-term outcome of anterior cruciate
      ligament reconstruction? A preliminary report.
AB  - INTRODUCTION: Anterior cruciate ligament (ACL) injury is often accompanied by
      injuries of the menisci. In order to restore knee stability, anterior cruciate
      ligament reconstruction (ACLR) is performed, with meniscus surgery when needed.
      The purpose of this study was to assess the medium-term outcome of ACLR in
      subjects with and without concomitant meniscus tear and partial meniscectomy.
      MATERIAL AND METHODS: We prospectively studied 73 patients after arthroscopically
      assisted bone-patellar tendon-bone ACLR. Subjects were divided into two
      subgroups: those who had only ACLR (group A, 54 subjects with mean age 28, (SD
      9)) and those who underwent both ACLR and concomitant partial meniscectomy (group
      B, 19 subjects, mean age 32 [11]). Subjects completed a disease-specific
      questionnaire, the Knee injury and Osteoarthritis Outcome Score (KOOS),
      preoperatively and at a minimum follow-up of 1 year. RESULTS: No differences in
      mean scores between group A and B were observed either preoperatively or at
      follow-up. We found a significant change in mean score in the KOOS subscale QoL
      in group A following ACLR (Delta = 9 points, p = 0.039). Most subjects improved
      in the KOOS subscales Sports and Recreation and QoL in both group A (59 and 52%
      respectively) and B (63 and 47% respectively). Eight subjects (15%) from group A
      and 1 (5%) from group B fulfilled criteria of functional recovery. Criteria of
      treatment failure were fulfilled in 17 subjects (32%) from A and 4 (21%) from
      group B. CONCLUSIONS: Patients undergoing ACLR with partial meniscectomy had a
      similar medium-term outcome compared to individuals with ACL tear alone.

PMID- 25395953
TI  - Years of life lost due to malignant neoplasms characterized by the highest
      mortality rate.
AB  - INTRODUCTION: The analysis of premature deaths measured with years of life lost
      between the studied and referential populations helps to emphasize the social and
      economic aspect of a loss caused by deaths due to malignant neoplasms. The aim of
      the study was to analyze years of life lost by inhabitants of the Lodz province
      due to malignant neoplasms. MATERIAL AND METHODS: The study material included a
      database which contained information gathered from 313,144 death certificates
      (including 66,899 people who died of malignant neoplasms) of inhabitants of the
      Lodz province who died between 1999 and 2008. The SEYLLp (Standard Expected Years
      of Life Lost per living person) method was used to determine years of life lost.
      Jointpoint models were used to analyze time trends. RESULTS: In males the
      diseases which mostly contributed to death were tracheal, bronchial and lung
      malignant neoplasms (SEYLLp = 170.7) and cancer of the large intestine, rectum
      and anus (SEYLLp = 47.5). In females the principal diseases were tracheal,
      bronchial and lung malignant neoplasms (SEYLLp = 61.6), breast cancer (SEYLLp =
      60.4) and cancer of the large intestine, rectum and anus (SEYLLp = 42.3). The
      years of life lost were growing in the period under study. CONCLUSIONS: The
      number of years lost due to malignant neoplasms in the Lodz province between 1999
      and 2008 was growing. The main reasons for deaths in females were tracheal,
      bronchial and lung malignant neoplasms as well as breast cancer and in males -
      cancer of the large intestine, rectum and anus as well as prostate cancer.

PMID- 25395954
TI  - Prognostic role of troponin and natriuretic peptides as biomarkers for
      deterioration of left ventricular ejection fraction after chemotherapy.
AB  - Cardiotoxicity due to anthracyclines, trastuzumab and other potential cardiotoxic
      drugs is still a problem of modern chemotherapy. For years researchers have tried
      to find biological markers that can predict changes in the heart. The most
      thoroughly tested markers are troponin and natriuretic peptides. Some studies
      have proven that these markers can indeed be useful. In studies which have shown
      the predictive role of troponin I the assessment of this marker was performed
      very frequently. It is not possible to carry out such serial measurements in many
      centers because of typical 1-day hospital stay times. The predictive role of
      natriuretic peptides still needs further investigation. This review considers the
      newest research from recent years. 

PMID- 25395955
TI  - Tuberculosis and diabetes mellitus - an underappreciated association.
AB  - The current review presents up-to-date knowledge on tuberculosis (TB) in diabetic
      patients. On the basis of available literature, there is little doubt about the
      close relationship between these two conditions. Diabetes mellitus in this
      association may still contribute substantially to the burden of TB and negatively
      affect control of the latter. Chronic hyperglycemia at least to some extent may
      alter the clinical manifestation, radiological appearance, treatment outcome and
      prognosis of TB. Although the pathogenesis is not clear, diabetes may impair both
      innate and adaptive immune responses to Mycobacterium tuberculosis. Eventually,
      effective screening and dual management of the diseases have to be addressed both
      in low- and high-income countries in order to limit the negative effects of the
      forthcoming global diabetes epidemic. 

PMID- 25395956
TI  - Relationship between single nucleotide polymorphisms in the 3'-untranslated
      region of the vascular endothelial growth factor gene and susceptibility to
      diabetic peripheral neuropathy in China.
AB  - INTRODUCTION: This study is to elucidate the relationship between a 936C/T
      mutation at the 3'-untranslated region of the human vascular endothelial growth
      factor (VEGF) gene and diabetic peripheral neuropathy (DPN). MATERIAL AND
      METHODS: All subjects recruited in this study were divided into DM (diabetes
      without neuropathy, retinopathy or nephropathy), DPN (diabetes with peripheral
      neuropathy only) and healthy control groups. The gene polymorphism was determined
      by polymerase chain reaction-restriction fragment length polymorphism, as well as
      other clinical methods including serum VEGF by ELISA. RESULTS: The C allele
      frequency and CC genotype frequency in the DPN group were higher than those in
      the NC group and DM group. The T allele frequency and CT+TT genotype (carrying
      the T allele) frequency in the DPN group were lower than those in the NC group
      (chi(2) = 19.051 and 18.533, both p < 0.001) and DM group (chi(2) = 11.117 and
      11.156, both p = 0.001). However, there was no statistically significant
      difference in the three genotype (CC/CT+TT) frequencies and allele (C/T)
      frequencies between the DM group and the NC group. The multivariate logistic
      regression analysis showed that the levels of glycated hemoglobin (HbA1c), total
      cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and plasma VEGF
      positively correlated with DPN, while the 936C/T gene polymorphism of VEGF
      negatively correlated with DPN. CONCLUSIONS: Allele 936C of VEGF may serve as a
      genetic marker susceptible to DPN, while allele 936T may be a protective genetic
      marker of DPN.

PMID- 25395957
TI  - Lung damage after long-term exposure of adult rats to sodium fluoride.
AB  - INTRODUCTION: Fluorides, when taken in amounts exceeding the standard therapeutic
      dosage, are regarded as toxic substances. Chronic fluorosis causes marked
      destruction of lung tissues. The study aimed to determine whether the effect of a
      chronic toxic dose of sodium fluoride on the lung of an adult male albino rat is
      reversible or irreversible. This was done through light and electron microscopic
      studies. Morphometric study was also done. MATERIAL AND METHODS: Forty adult male
      rats were used. The animals were divided into 3 groups: control group; group I
      (chronic fluorosis group) in which sodium fluoride was given daily for 3 months;
      and group II (recovery group) in which sodium fluoride was given daily for 3
      months and after that the rats survived for another month. RESULTS: The lung of
      group I was characterized by presence of blood and lymph congestion. Thickening
      of alveolar septa was also observed with rupture of septa and widening of the air
      spaces. The area % of collagen (1.13 +/-0.5), septal wall thickness (13.47 +/
      6.1), and number of macrophages (5 +/-2.5) increased in comparison to the control
      group (p <= 0.05). With discontinuation of sodium fluoride (group II), no much
      improvement was observed. CONCLUSIONS: Chronic fluorosis has many pathological
      effects on the lung which are irreversible.

PMID- 25395958
TI  - Effect of carbon dioxide pneumoperitoneum on human renal cell carcinoma
      proliferation and metastasis in an orthotropic xenograft nude mouse model.
AB  - INTRODUCTION: This study aimed to explore the effect of carbon dioxide (CO2)
      pneumoperitoneum on tumor proliferation and metastasis in an orthotropic
      xenograft nude mice model of human renal cell carcinoma (RCC) and evaluate the
      safety of CO2 pneumoperitoneum laparoscopy for treating RCC. MATERIAL AND
      METHODS: RCC 786-0 cells were injected to establish an orthotropic xenograft
      model. Fifty nude mice were given orthotropic inoculations and randomized to five
      groups: group A (control); group B (CO2 pneumoperitoneum for 2 h); group C (CO2
      pneumoperitoneum for 4 h); group D (CO2 pneumoperitoneum for 4 h and 24 h after
      waking); group E (CO2 pneumoperitoneum for 4 h and 48 h after waking). The
      proliferation status was observed in RCC specimens by immunohistochemical
      staining for Ki67. The protein levels of hypoxia-inducible factor-1alpha (HIF
      1alpha) and vascular endothelial growth factor (VEGF) were examined by western
      blotting. RESULTS: All groups showed similar Ki67-positive staining in RCC
      samples (p > 0.05). The relative expression of HIF-1alpha and VEGF gradually
      increased in both group B and group C, as compared with group A, but only the
      difference between group C and group A reached statistical significance (p <
      0.05). The protein levels of HIF-1alpha and VEGF decreased in both group D and
      group E, as compared with group B and group C; however, the differences between
      group D, group E, and group A did not reach statistical significance (p > 0.05).
      CONCLUSIONS: In an orthotropic xenograft nude mice model of RCC, CO2
      pneumoperitoneum has no effect on expression of the cellular proliferation marker
      Ki67. However, CO2 pneumoperitoneum rapidly induces transient expression of HIF
      1alpha and VEGF. Thus, CO2 pneumoperitoneum laparoscopy may be a safe method for
      treating RCC.

PMID- 25395959
TI  - Telemedicine system for the care of patients with neuromuscular disease and
      chronic respiratory failure.
AB  - INTRODUCTION: Neuromuscular diseases cause a number of limitations which may be
      improved by using a telemedicine system. These include functional impairment and
      dependence associated with muscle weakness, the insidious development of
      respiratory failure and episodes of exacerbation. MATERIAL AND METHODS: The
      present study involved three patients with severe neuromuscular disease, chronic
      respiratory failure and long-term mechanical ventilation, who were followed up
      using a telemedicine platform. The telemedicine system is based on
      videoconferencing and telemonitoring of cardiorespiratory variables (oxygen
      saturation, heart rate, blood pressure and electrocardiogram). Two different
      protocols were followed depending on whether the patient condition was stable or
      unstable. RESULTS: Over a period of 5 years, we analyzed a series of variables
      including use of the system, patient satisfaction and clinical impact. Overall we
      performed 290 videoconference sessions, 269 short monitoring oximetry
      measurements and 110 blood pressure measurements. With respect to the clinical
      impact, after enrolment in the telemedicine program, the total number of hospital
      admissions fell from 18 to 3. CONCLUSIONS: Our findings indicate that the system
      was user friendly for patients and care givers. Patient satisfaction scores were
      acceptable. The telemedicine system was effective for the home treatment of three
      patients with severe neuromuscular diseases and reduced the need for hospital
      admissions.

PMID- 25395960
TI  - A novel noninvasive assessment of hepatic venous pressure gradient and portal
      pressure computed from computed tomography angiography.

PMID- 25395961
TI  - Natural killer cell-mediated immune deficiency or compromise in patients with
      portopulmonary hypertension.

PMID- 25395962
TI  - A case of recurrent malignant fibrous histiocytoma with marked response to
      combined chemotherapy with gemcitabine and carboplatin.

PMID- 25395963
TI  - Papillary carcinoma in thyroglossal duct cyst with uninvolved thyroid. Case
      report and review of the literature.

PMID- 25395964
TI  - A forgotten oat head aspiration in an adult patient.

PMID- 25395966
TI  - Psychiatry in former socialist countries: implications for north korean
      psychiatry.
AB  - Very little information is available regarding psychiatry in North Korea, which
      is based on the legacy of Soviet psychiatry. This paper reviews the
      characteristics of psychiatry in former socialist countries and discusses its
      implications for North Korean psychiatry. Under socialism, psychiatric disorders
      were attributed primarily to neurophysiologic or neurobiological origins.
      Psychosocial or psychodynamic etiology was denied or distorted in line with the
      political ideology of the Communist Party. Psychiatry was primarily concerned
      with psychotic disorders, and this diagnostic category was sometimes applied
      based on political considerations. Neurotic disorders were ignored by psychiatry
      or were regarded as the remnants of capitalism. Several neurotic disorders
      characterized by high levels of somatization were considered to be neurological
      or physical in nature. The majority of "mental patients" were institutionalized
      for a long periods in large-scale psychiatric hospitals. Treatment of psychiatric
      disorders depended largely on a few outdated biological therapies. In former
      socialist countries, psychodynamic psychotherapy was not common, and psychiatric
      patients were likely to experience social stigma. According to North Korean
      doctors living in South Korea, North Korean psychiatry is heavily influenced by
      the aforementioned traditions of psychiatry. During the post-socialist
      transition, the suicide rate in many of these countries dramatically increased.
      Given such mental health crises in post-socialist transitional societies, the
      field of psychiatry may face major challenges in a future unified Korea. 

PMID- 25395965
TI  - Circadian polymorphisms in night owls, in bipolars, and in non-24-hour sleep
      cycles.
AB  - People called night owls habitually have late bedtimes and late times of arising,
      sometimes suffering a heritable circadian disturbance called delayed sleep phase
      syndrome (DSPS). Those with DSPS, those with more severe progressively-late non
      24-hour sleep-wake cycles, and those with bipolar disorder may share genetic
      tendencies for slowed or delayed circadian cycles. We searched for polymorphisms
      associated with DSPS in a case-control study of DSPS research participants and a
      separate study of Sleep Center patients undergoing polysomnography. In 45
      participants, we resequenced portions of 15 circadian genes to identify unknown
      polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar
      comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both
      larger samples, using Illumina Golden Gate assays. Associations of SNPs with the
      DSPS phenotype and with the morningness-eveningness parametric phenotype were
      computed for both samples, then combined for meta-analyses. Delayed sleep and
      "eveningness" were inversely associated with loci in circadian genes NFIL3
      (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was
      associated with non-24-hour sleep-wake cycles, and less robustly, with delayed
      sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and
      rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright
      light and melatonin can palliate circadian disorders, and genetics may clarify
      the underlying circadian photoperiodic mechanisms. After further replication and
      identification of the causal polymorphisms, these findings may point to future
      treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or
      depression. 

PMID- 25395967
TI  - A Meta-Analysis Comparing Open-Label versus Placebo-Controlled Clinical Trials
      for Aripiprazole Augmentation in the Treatment of Major Depressive Disorder:
      Lessons and Promises.
AB  - OBJECTIVE: The present study is to provide whether open-label studies (OLS) may
      properly foresee the efficacy of randomized, placebo-controlled trials (RCTs)
      using OLSs and RCTs data for aripiprazole in the treatment of MDD, with the use
      of meta-analysis approach. METHODS: A search of the studies used the key terms
      "depression and aripiprazole" from the databases of PubMed/PsychInfo from Jan
      2005 through July 2013. The data were selected and verified for publication in
      English-based peer-reviewed journals based on rigorous inclusion criteria.
      Extracted data were delivered into and run by the Comprehensive Meta Analysis
      program v2. RESULTS: The pooled SMDs for the primary efficacy measure was
      statistically significant, pointing out the significant reduction of depressive
      symptoms after aripiprazole augmentation (AA) to current antidepressant treatment
      in OLSs (pooled SMD=-2.114, z=-9.625, p<0.001); similar results were also found
      in RCTs (pooled SMD=-2.202, z=-6.862, p<0.001). The meta-regression analysis
      revealed no influence of the study design for treatment outcome. CONCLUSION:
      There was no difference in the treatment effects of aripiprazole as an
      augmentation therapy in both OLSs and RCTs, indicating that open-label design may
      be a potentially useful predictor for treatment outcomes of controlled-clinical
      trials. The proper conduction of OLSs may provide informative, useful and
      preliminary clinical data and factors to be involved in controlled-clinical
      trials, by which we may have better understanding on the role of AA (e.g., dosing
      issues, proper duration of treatment, specific population for AA) implicated in
      the treatment of MDD in clinical practice.

PMID- 25395968
TI  - Psychosocial risk factors associated with internet addiction in Korea.
AB  - OBJECTIVE: The aim of this study was to examine the prevalence of Internet
      addiction in middle school students and to identify associated psychosocial risk
      factors and depression. METHODS: This study was part of a larger epidemiological
      study on childhood psychiatric disorders conducted in Osan, a city of Republic of
      Korea. We used IAS for internet addiction, K-YSR for subjects' emotional and
      behavioral problems and K-CDI for depressive symptoms. We used the data of n=1217
      completed cases. We put on independent variables, which are sex, age, smoking and
      alcohol experiences, economic status, age of first Internet use, K-YSR and K-CDI
      score. RESULTS: The subjects consisted of addicted users (2.38%), over users
      (36.89%) and normal Internet users (60.72%). Attention problems, sex, delinquent
      problems, K-CDI scores, thought problems, age and aggressive behavior were
      predictable variables of internet addiction. Age of initial Internet use
      negatively predicted Internet addiction. CONCLUSION: This result showed similar
      to other researches about sociodemographic, emotional or behavioral factors
      related to internet addiction. Generally, subjects with more severe internet
      addiction had more emotional or behavioral problems. It means that they already
      have had various difficulties when we found internet addiction of adolescents.
      Therefore it is necessary to evaluate whether the subjects have any emotional or
      behavioral troubles and to intervene to prevent internet addiction.

PMID- 25395969
TI  - The Difference in Comorbidities and Behavioral Aspects between Internet Abuse and
      Internet Dependence in Korean Male Adolescents.
AB  - OBJECTIVE: This study examined the differences in psychiatric comorbidities and
      behavioral aspects in accordance with the severity of Internet addiction in male
      adolescents. METHODS: One hundred and twenty-five adolescents from four middle
      and high schools in Seoul were enrolled in this study. The subjects were divided
      into non-addict, abuse, and dependence groups according to a diagnostic interview
      by psychiatrists. The psychiatric comorbidities and behavioral aspects of
      subjects were evaluated through psychiatric clinical interviews based on the
      Diagnostic and Statistical Manual of Mental Disorders (4th edition), the
      Children's Depression Inventory, the State-Trait Anxiety Inventory, the Internet
      Addiction Test, and a self-reported questionnaire about behavioral aspects.
      RESULTS: The psychiatric comorbidity distributions were significantly different
      in the abuse and dependence groups, particularly in terms of attention-deficit
      hyperactivity disorder and mood disorder items. The Children's Depression
      Inventory, the State-Trait Anxiety Inventory, and the Internet Addiction Test
      scores were also significantly different among the three groups. There were
      significant differences in 10 of the 20 items of the Internet Addiction Test
      between the non-addict, abuse, and dependence groups. There were significant
      differences in seven items between the non-addict and abuse groups, but no
      differences between subjects in the abuse and dependence groups. Significant
      differences were observed in three items between the abuse and dependence groups,
      but there were no significant differences between the non-addict and abuse
      groups. In terms of behavioral aspects, scores for abusive, sexual, and decreased
      social interest behaviors were highest in the dependence group, and lowest in the
      non-addict group. However, the behavioral aspects of decreased interpersonal
      relationships did not show this difference between groups. CONCLUSION: This study
      suggests that there are differences in psychiatric comorbidities and behavioral
      aspects between adolescent males with characteristics of Internet abuse and
      Internet dependence.

PMID- 25395970
TI  - A preliminary validity study of the cambridge neuropsychological test automated
      battery for the assessment of executive function in schizophrenia and bipolar
      disorder.
AB  - OBJECTIVE: Although the executive function subtests of the Cambridge
      Neuropsychological Test Automated Battery (CANTAB) have been used to assess
      cognitive function in diverse psychiatric illnesses, few studies have verified
      the validity of this battery for Korean psychiatric patients. Therefore, this
      preliminary study evaluated the construct and concurrent validity of the
      executive function subtests of the CANTAB for Korean psychiatric patients by
      comparing it with subtests of the Computerized Neuropsychological Test (CNT).
      METHODS: Three subtests of the CANTAB and three subtests of the CNT were
      administered to 36 patients diagnosed with either schizophrenia or bipolar
      disorder. Subtests of the CANTAB included the Intra/Extra-Dimensional Set Shift
      (IED), Stockings of Cambridge (SOC), and Spatial Working Memory (SWM).
      Differences between groups on each subtest as well as correlations between the
      subtests of the CANTAB and the CNT were assessed. RESULTS: The schizophrenia
      group performed significantly more poorly on the IED and the Wisconsin Card
      Sorting Test (WCST) compared with the bipolar disorder group. Additionally,
      correlation analyses revealed a significant correlation between the IED and the
      WCST; a positive correlation between the SOC and the Trail Making Test, Part B
      and the Stroop test; and a significant correlation between the SWM and the Stroop
      test. CONCLUSION: This study verified the construct and concurrent validity of
      the executive function subtests of the CANTAB for Korean psychiatric patients and
      suggests that the subtests of this battery would be useful and appropriate for
      assessing deficits in executive function in Korean clinical settings.

PMID- 25395971
TI  - Psychosocial, physical, and autonomic correlates of depression in korean adults:
      results from a county-based depression screening study.
AB  - OBJECTIVE: We aimed to investigate the prevalence and psychosocial and
      neurophysiological correlates of depression in a large county-based cohort of
      Korean adults. METHODS: We recruited 2355 adults from a rural county-based health
      promotion program. The following psychometric scales were used: the Center for
      Epidemiologic Studies Depression scale (CES-D) was used to assess depression, the
      General Health Questionnaire (GHQ) was used to evaluate stress, and the Medical
      Outcome Study Social Support Survey (MOS-SSS) was used to determine perceived
      social support. Heart rate variability (HRV) was used to assess
      neurophysiological properties. The psychosocial and neurophysiological variables
      of adults with depression (CES-D score >=25) and without depression (CES-D score
      <25) were statistically compared. A logistic regression model was constructed to
      identify factors independently associated with depression. RESULTS: We estimated
      that 17.7% of the subjects had depression, which was associated with old age,
      being female, being single, less religious affiliation, high education, low body
      mass index (BMI), low levels of aerobic exercise, low social support, and a low
      HRV triangular index. The explanatory factors of depression included high
      education, less religious affiliation, low levels of current aerobic exercise,
      low BMI, and low social support. CONCLUSION: Given the relatively high prevalence
      of overall depression, subsyndromal depression should also be regarded as an
      important issue in screening. The independent factors associated with depression
      suggest that practical psychosocial intervention, including brief psychotherapy,
      aerobic exercise, and other self-help methods should be considered. In addition,
      the HRV results suggest that further depression screening accompanied by
      neurophysiological features would require fine methodological modifications with
      proactive efforts to prevent depressive symptoms.

PMID- 25395972
TI  - Clinical characteristics of the respiratory subtype in panic disorder patients.
AB  - OBJECTIVE: Panic disorder has been suggested to be divided into the respiratory
      and non-respiratory subtypes in terms of its clinical presentations. The present
      study aimed to investigate whether there are any differences in treatment
      response and clinical characteristics between the respiratory and non-respiratory
      subtypes of panic disorder patients. METHODS: Among the 48 patients those who
      completed the study, 25 panic disorder patients were classified as the
      respiratory subtype, whereas 23 panic disorder patients were classified as the
      non-respiratory subtype. All patients were treated with escitalopram or
      paroxetine for 12 weeks. We measured clinical and psychological characteristics
      before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS),
      Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised
      (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating
      Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D). RESULTS: The
      prevalence of the agoraphobia was significantly higher in the respiratory group
      than the non-respiratory group although there were no differences in gender and
      medication between the two groups. The respiratory group showed higher scores on
      the fear of respiratory symptoms of the ASI-R. In addition, after
      pharmacotherapy, the respiratory group showed more improvement in panic symptoms
      than the non-respiratory group. CONCLUSION: Panic disorder patients with the
      respiratory subtype showed more severe clinical presentations, but a greater
      treatment response to SSRIs than those with non-respiratory subtype. Thus,
      classification of panic disorder patients as respiratory and non-respiratory
      subtypes may be useful to predict clinical course and treatment response to
      SSRIs.

PMID- 25395973
TI  - Application of the seven-factor-model of personality to an italian preschool
      sample.
AB  - OBJECTIVE: Advances in dimensional assessment of children in healthy and clinical
      populations has renewed interest in the study of temperament. Cloninger's
      Temperament and Character Inventory (TCI) has shown high reliability and internal
      consistency. Adult and adolescent versions have been translated into a number of
      languages and validated in cross-cultural studies worldwide. To date only one
      preschool-TCI-based study has been conducted in early infancy with teachers as
      observers. The present study is aimed to test an Italian Preschool version of the
      Temperament and Character Inventory (PsTCI). This is the first replication and
      the first validation study of TCI on preschoolers with parents as observers.
      METHODS: 395 preschool children, recruited from pediatric communities and day
      care centres throughout Italy, participated in the study. Parents of each child
      enrolled in the study and completed a PsTCI about the child. Standard
      psychometric tests of reliability and validation were performed. RESULTS:
      Exploratory factor analyses demonstrated the presence of distinct domains for
      temperament and character. TCI dimensions had good internal consistency with
      Cronbach's alpha ranging values (|0.60|-|0.81|). Gender differences were found
      for Harm Avoidance (beta=-0.186; p<=0.001) and Self-Directedness (beta=-0.216;
      p<=0.01), and accounted for 5-35arm-38-702- of the observed variance. CONCLUSION:
      The present work suggests the psychological complexity of Cloninger's model and
      confirms its application in pre-school children from diverse environmental and
      cultural backgrounds. The results confirm that Cloninger's instrument for
      temperament and character evaluations can also be used with different observers
      and highlight the importance of considering cultural and demographic differences
      in the assessment of temperament and character in preschoolers.

PMID- 25395974
TI  - Altitude may contribute to regional variation in methamphetamine use in the
      United States: a population database study.
AB  - OBJECTIVE: Methamphetamine (MA) use rates in the United States (US) have
      consistently demonstrated geographical variation and have been higher in the West
      and Midwest. This uneven pattern of use could be explained by regional
      differences in MA manufacturing and distribution, but may also result from
      differences in altitude. The hypobaric hypoxia found at high altitude alters
      neurotransmitter synthesis in the brain, which may contribute to MA use. The
      present study investigated the relationship between mean altitude and MA use rate
      in the 48 contiguous US states and the District of Columbia. METHODS: State-level
      estimates of past year MA use were extracted from the National Survey on Drug Use
      and Health report. The mean altitude of each state was calculated using the
      Shuttle Radar Topography Mission altitude data set. RESULTS: There was a
      significant positive correlation between mean state altitude and MA use rate
      (r=0.66, p<0.0001). Multivariate linear regression analysis showed that altitude
      remained a significant predictor for MA use rate (beta=0.36, p=0.02), after
      adjusting for age, ethnicity, education, socioeconomic level, employment, MA
      laboratory incidents, subpopulations, and other substance use. CONCLUSION:
      Altitude appears to a possible contributing factor for regional variation of MA
      use in the US. Further studies will be required to determine biological changes
      in neurotransmission resulting from chronic mild hypoxia at high altitude in MA
      users.

PMID- 25395975
TI  - The Mediating Effects of Self-Esteem and Optimism on the Relationship between
      Quality of Life and Depressive Symptoms of Breast Cancer Patients.
AB  - OBJECTIVE: This study investigated the mediating effects of the internal
      psychological factors of self-esteem and optimism on the relationship between
      breast cancer patients' quality of life in terms of symptoms and functioning and
      depressive symptoms. METHODS: The study centered on 384 breast cancer patients
      who had within a 24-month period received diagnosis of 0-4 stage cancer and had
      medical treatment. To achieve the study's purpose, the study made use of EORTC
      QLQ BR23, CES-D, and the Self-Esteem and Optimism Scales. RESULTS: Findings
      revealed that breast cancer patients' quality of life was negatively impacted by
      self-esteem and optimism, and that self-esteem and optimism impacted negatively
      on depressive symptoms. Analyses showed that when breast cancer patients' quality
      of life affects depressive symptoms, the full mediation effect of self-esteem was
      statistically significant. Also, findings revealed there to be a significant
      partial mediation effect due to optimism. CONCLUSION: Study findings demonstrated
      that enhancing self-esteem is crucial in the psychological intervention of
      depressive symptoms because self-esteem functioned as the main causal factor
      accounting for all variation when breast cancer patients' quality of life
      affected depressive symptoms. In addition, results suggested that optimism is
      also vital to psychological intervention because it functioned as partial cause
      of heightened depressive symptoms when breast cancer patients' quality of life
      affected depressive symptoms.

PMID- 25395976
TI  - A normative study of the disability assessment for dementia in community-dwelling
      elderly koreans.
AB  - OBJECTIVE: We investigated demographic influences on Korean version of Disability
      Assessment for Dementia (DAD-K) performance and developed normative data for DAD
      K. METHODS: The DAD-K was administered to 2362 normal controls (NCs), 296
      patients with mild cognitive impairment (MCI) and 293 patients with Alzheimer's
      disease (AD). MANOVA and ROC curve analysis were used to compare DAD-K
      performance and the diagnostic accuracy of DAD-K, respectively. The demographic
      influence on DAD-K scores was analyzed by multiple linear regression and ANOVA.
      Normative DAD-K data were calculated using natural logarithmic transformation.
      RESULTS: All DAD-K scores were significantly different among groups (p<0.001).
      Post hoc analysis showed that instrumental activities of daily living (IADL),
      executive function and DAD-K total scores began to decline significantly in the
      very mild stage of AD, whereas the basic activities of daily living (BADL) scores
      began to decline in the mild stage of AD. The area under the ROC curve
      differentiating MCI or AD from NC was 0.737 and that differentiating AD from MCI
      or NC was 0.911. IADL and planning and organization scores were influenced by age
      and education and performance and DAD-K total scores were influenced by
      education. CONCLUSION: The demographic influences on DAD-K scores are not
      conspicuous and are mainly limited to the IADL and planning and organization
      scores. Unitary or minimally stratified norms for a specific population were
      developed for DAD-K application. Our results suggest that the DAD-K is useful for
      differentiating NC or MCI from AD but not as powerful for differentiating NC from
      MCI.

PMID- 25395977
TI  - Effects of clozapine, haloperidol, and fluoxetine on the reversal of cocaine
      induced locomotor sensitization.
AB  - OBJECTIVE: Repeated treatment with psychostimulants induces sensitization of the
      dopaminergic system in the brain. Dopaminergic sensitization has been proposed as
      a mechanism of psychosis. Although antipsychotics block the expression of
      sensitized behavior, they are ineffective for reversing the sensitized state. We
      investigated the effect of clozapine, haloperidol, and fluoxetine on the reversal
      of cocaine-induced behavioral sensitization. METHODS: Male ICR mice were
      sensitized to cocaine with repeated treatment. Animals were then split into four
      groups, and each group was treated with vehicle or one of the above drugs for 5
      days. After a 3-day drug washout, locomotor activity was assessed before and
      after a cocaine challenge. RESULTS: Clozapine reversed the sensitized state,
      whereas haloperidol did not. Fluoxetine seemed to reverse the sensitization
      partially. CONCLUSION: We confirmed that D2 blockade was not effective for
      reversing sensitization. The reversal by clozapine is partially explained in
      terms of its strong 5-HT2 and weak D2 affinity. The partial reversal by
      fluoxetine seemed to be related to its serotonin-augmenting action.

PMID- 25395978
TI  - The effectiveness of cross-tapering switching to ziprasidone in patients with
      schizophrenia or schizoaffective disorder.
AB  - OBJECTIVE: Switching antipsychotics is one useful therapeutic option when the
      treatment of schizophrenia encounters suboptimal efficacy and intolerability
      issues. This study aimed to investigate the efficacy and tolerability of cross
      tapering switching to ziprasidone from other antipsychotics. METHODS: A total of
      67 patients with schizophrenia or schizoaffective disorder were recruited in this
      12-week, multicenter, non-comparative, open-label trial. Prior antipsychotics
      were allowed to be maintained for up to 4 weeks during the titration of
      ziprasidone. Efficacy was primarily measured using the 18-item Brief Psychotic
      Rating Scale (BPRS) at baseline, 4 weeks, 8 weeks, and 12 weeks. Efficacy was
      secondarily measured by the Clinical Global Impression-Severity (CGI-S) scale and
      the Global Assessment of Functioning (GAF) scale at each visit. Regarding the
      metabolic effects of switching to ziprasidone, weight, body mass index (BMI),
      waist-to-hip ratio (WHR), and lipid profile-including triglyceride (TG), high
      density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol
      levels-were measured at each follow-up visit. RESULTS: The BPRS scores were
      significantly improved at 12 weeks after switching to ziprasidone (F=5.96,
      df=2.11, p=0.003), whereas the CGI-S and GAF scores were not significantly
      changed. BMIs, WHRs, and TG levels were significantly decreased, with no
      significant changes in other lipid profiles. CONCLUSION: Cross-tapering switching
      to ziprasidone is effective for patients with schizophrenia spectrum disorders.
      Beyond the efficacy of the procedure, favorable metabolic profiles show that
      switching to ziprasidone may be helpful for maintenance therapy over an extended
      period.

PMID- 25395979
TI  - Schneiderian first rank symptoms and gamma oscillatory activity in neuroleptic
      naive first episode schizophrenia: a 192 channel EEG study.
AB  - OBJECTIVE: Schneiderian first-rank symptoms (FRS) and abnormal EEG gamma activity
      in schizophrenia have been reported independently to have a neurodevelopmental
      basis. We aimed to investigate spontaneous gamma power in two groups of first
      episode schizophrenia patients (those who experience FRS and those who do not).
      METHODS: A comparative hospital based study having 37neuroleptic naive male
      patients with schizophrenia divided into two groups-FRS(+) and FRS(-) groups
      based on the presence of FRS. Thirty age, sex, education and handedness matched
      individuals served as controls (N). All participants underwent a 192-channel
      resting Electroencephalography (EEG) recording. Gamma spectral power was
      calculated for low- (30-50 Hz) and high-gamma 1 & 2 (51-70 and 71-100 Hz) bands.
      Spectral power was compared between three groups using MANOVA and supplementary
      one-way ANOVA with Bonferroni test controlling for multiple comparisons. Linear
      regression was used to identifying predictor variables for FRS. Pearson
      correlation coefficient was computed between spectral power parameters and
      various clinical variables. RESULTS: Significantly higher high gamma band-1 power
      was observed over right frontal (p<0.05), parietal (p<0.05) and temporal (p<0.05)
      regions in FRS(+) than FRS(-) group and normal controls. Right parietal high
      gamma-1 power and paranoid cluster on PANSS significantly predicted number of FRS
      in total schizophrenia patients; paranoid cluster on PANSS showed significant
      correlation with number of FRS in FRS(+) group. CONCLUSION: Findings of our study
      add to the evidence that areas contained within the hetero modal association
      cortex are associated with FRS. The study findings also strengthen the
      neurodevelopmental basis of FRS in schizophrenia.

PMID- 25395980
TI  - Association of SNAP-25 Gene Ddel and Mnll Polymorphisms with Adult Attention
      Deficit Hyperactivity Disorder.
AB  - OBJECTIVE: The synaptosomal-associated protein of 25 kDa (SNAP-25) gene is a
      presynaptic plasma membrane protein and an integral component of the vesicle
      docking and fusion machinery mediating secretion of neurotransmitters.
      Previously, several studies reported association between SNAP-25 and attention
      deficit hyperactivity disorder (ADHD). We investigated whether these SNAP-25
      polymorphisms (MnlI T/G and DdelI T/C) were also associated with ADHD in the
      Turkish population. METHODS: Our study comprised unrelated 139 subjects who met
      DSM-IV criteria for ADHD and 73 controls and all were of Turkish origin. Genetic
      analyses were performed and patients were evaluated with Wender-Utah Rating Scale
      and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. RESULTS:
      SNAP-25 DdelI polymorphism was not associated with ADHD but there was a
      statistically significant difference between ADHD patients and controls for SNAP
      25 MnlI polymorphism. For SNAP-25 MnlI polymorphism patients with G/G genotype of
      the SNAP-25 gene MnlI polymorphism had higher Wender-Utah scores and higher
      scores in the 1st and 3rd parts of adult ADD/ADHD Scale. CONCLUSION: We detected
      a significant association of the MnlI polymorphism in our ADHD sample which was
      similar to previous findings. Our study also revealed that SNAP-25 MnlI
      polymorphism was also associated with symptom severity of ADHD. This study is
      also, the first report on the association of SNAP-25 with ADHD in the Turkish
      population.

PMID- 25395981
TI  - Abelson helper integration site-1 gene variants on major depressive disorder and
      bipolar disorder.
AB  - OBJECTIVE: The present study aimed to explore whether 4 single nucleotide
      polymorphisms (SNPs) within the AHI1 gene could be associated with major
      depressive disorder (MD) and bipolar disorder (BD), and whether they could
      predict clinical outcomes in mood disorders. METHODS: One hundred and eighty-four
      (184) patients with MD, 170 patients with BD and 170 healthy controls were
      genotyped for 4 AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501).
      Baseline and final clinical measures for MD patients were assessed through the
      Hamilton Rating Scale for Depression (HAM-D). Allelic and genotypic frequencies
      in MD and BD subjects were compared with those of each disorder and healthy group
      using the chi(2) statistics. Repeated measures ANOVA was used to test possible
      influences of SNPs on treatment efficacy. RESULTS: The rs9647635 A/A was more
      represented in subjects with BD as compared with MD and healthy subjects
      together. The rs9647635 A/A was also more presented in patients with MD than in
      healthy subjects. With regard to the allelic analysis, rs9647635 A allele was
      more represented in subjects with BD compared with healthy subjects, while it was
      not observed between patients with MD and healthy subjects. CONCLUSION: Our
      findings provide potential evidence of an association between some variants of
      AHI1 and mood disorders susceptibility but not with clinical outcomes. However,
      we will need to do more adequately-powered and advanced association studies to
      draw any conclusion due to clear limitations.

PMID- 25395982
TI  - Delay in the recovery of normal sleep-wake cycle after disruption of the light
      dark cycle in mice: a bipolar disorder-prone animal model?
AB  - OBJECTIVE: Disruption of the circadian rhythm is known as a provoking factor for
      manic episodes. Individual differences exist in the recovery rate from disruption
      in the general population. To develop a screening method to detect individuals
      vulnerable to bipolar disorder, the authors observed the relationship between the
      recovery of the normal sleep-wake cycle after switching the light-dark (LD) cycle
      and quinpirole-induced hyperactivity in mice. METHODS: Sixteen male mice (age of
      5 weeks, weight 28-29 gm) were subjected to a circadian rhythm disruption
      protocol. Sleep-wake behaviors were checked every 5 min for a total duration of
      15 days, i.e., 2 days of baseline observations, 3 days of LD cycle changes, and
      10 days of recovery. During the dark cycle on the 16th experimental day, their
      general locomotor activities were measured in an open field for 120 minutes after
      an injection of quinpirole (0.5 mg/kg, s.c.). RESULTS: The individual differences
      in the recovery rate of the baseline sleep-wake cycle were noted after 3 days of
      switching the LD cycle. Fifty percent (n=8) of the mice returned to the baseline
      cycle within 6 days after normalizing the LD cycle (early recovery group). The
      locomotor activities of mice that failed to recover within 6 days (delayed
      recovery group) were significantly higher (mean rank=12.25) than those of the
      early recovery group (mean rank=4.75, u=62.0, p=0.001, Mann-Whitney U test).
      CONCLUSION: Given that the quinpirole-induced hyperactivity is an animal model of
      bipolar disorder, our results suggest individuals who have difficulties in
      recovery from circadian rhythm disruption may be vulnerable to bipolar disorder.

PMID- 25395983
TI  - High altitude remains associated with elevated suicide rates after adjusting for
      socioeconomic status: a study from South Korea.
AB  - There have been several studies supporting a possible relationship between high
      suicide rate and high altitude. However socioeconomic status may confound this
      association because low socioeconomic status, which is known to be related to a
      high suicide rate, is also associated with living at high altitude. This study
      aims to explore whether the relationship between high altitude and high suicide
      rate remains after adjusting for socioeconomic status in South Korea. We
      collected demographic data of completed suicides, the mean altitude of the
      district where each suicide took place, and the mean income of each district. We
      analyzed the data using regression analysis before and after adjustment for mean
      income. We found that there is a positive correlation between altitude and
      suicide rate, even after adjustment for mean income. Thus, altitude appears to be
      an independent risk factor for suicide. 

PMID- 25395984
TI  - Depression and somatic symptoms may influence on chronic prostatitis/chronic
      pelvic pain syndrome: a preliminary study.
AB  - The present study is the first one to investigate the impacts of depression and
      somatization on the disease severity and quality of life (QoL) in patients with
      chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The Korean version of
      National Institutes of Health (NIH)- Chronic Prostatitis Symptom Index (CPSI) for
      severity of CP/CPPS. Korean version of Patient Health Questionnaire-9 (PHQ-9) for
      depression, Korean version of Patient Health Questionnaire-15 (PHQ-15) for
      somatization, and Korean version of EuroQol Questionnaire-5 Dimensions (EQ-5D)-
      [(EQ-5D utility index and visual analog scale (EQ-5D VAS)] for QoL, were
      administered. Eighty patients were enrolled. The NIH-CPSI total scores were
      significantly higher in those with depression (25.3%, p=0.01) or somatization
      (23.2%, p=0.03) than in those without. These trends toward significantly negative
      influence of depression and somatic symptoms on QoL were also observed. Our
      preliminary results indicate that depression and somatization may have negative
      influence on the symptom severity and QoL in patients with CP/CPPS. However,
      adequately-powered and more well-designed studies are mandatory to prove our
      results. 

PMID- 25395985
TI  - A case of intractable suspected perilymph fistula with severe depression.
AB  - A 68-year-old woman presented dizziness whenever she put her finger into the
      right ear and also complained of water-streaming tinnitus, which indicated she
      would have been suffering from perilymph fistula. An exploratory tympanotomy was
      conducted. Leakage of perilymph from the round window was suspected, although the
      cochlin-tomoprotein (CTP) results were negative. After the procedure, the
      patient's finger-induced dizziness, tinnitus, and vertigo spells disappeared
      completely. However, her dizzy symptom did not improve. The patient also
      complained of general fatigue, weight loss, and insomnia, which led us to suspect
      comorbid depression. Antidepressants and vestibular rehabilitation treatment
      resulted in a significant improvement in her dizziness. Although it is not
      apparent whether the patient had a perilymph fistula, this case demonstrates the
      importance of evaluating not only physical symptoms but also psychological
      comorbidity, especially when the physical symptoms are intractable despite
      treatment. 

PMID- 25395986
TI  - Prioritizing industries for occupational injury prevention and research in the
      Services Sector in Washington State, 2002-2010.
AB  - BACKGROUND: The Services Sector, as defined by the National Occupational Research
      Agenda (NORA), is comprised of a diverse industry mix and its workers face a
      variety of occupational exposures and hazards. The objective of this study was to
      identify high-risk industry groups within the Services Sector for prevention
      targeting. METHODS: Compensable Washington State workers' compensation claims
      from the Services Sector from 2002 through 2010 were analyzed. A "prevention
      index" (PI), the average of the rank orders of claim count and claim incidence
      rate, was used to rank 87 Services Sector industry groups by seven injury types:
      Work- Related Musculoskeletal Disorders (WMSDs), Fall to Lower Level, Fall on
      Same Level, Struck By/Against, Caught In/Under/Between, Motor Vehicle, and
      Overexertion. In the PI rankings, industry groups with high injury burdens appear
      higher ranked than industry groups with low counts or low rates of injury,
      indicating a need for prioritizing injury prevention efforts in these groups.
      RESULTS: In the Services Sector, these 7 injury types account for 84% of
      compensable claims in WA. The industry groups highest ranked by PI across the
      injury types included: Services to Buildings and Dwellings; Executive,
      Legislative, and Other General Government Support; and Waste Collection. WMSDs
      had the highest compensable claims rates. CONCLUSIONS: Services is a large sector
      of the economy, and the substantial number, rate, and cost of occupational
      injuries within this sector should be addressed. Several Services Sector industry
      groups are at high risk for a variety of occupational injuries. Using a PI to
      rank industry groups based on their injury risk provides information with which
      to guide prevention efforts.

PMID- 25395987
TI  - High-risk human papilloma virus and cervical abnormalities in HIV-infected women
      with normal cervical cytology.
AB  - BACKGROUND: The prevalence of High-Risk Human papilloma virus (HR-HPV), a
      necessary cause of invasive cervical cancer (ICC) is relatively high in HIV
      infected women. Gaps exist in our knowledge of the optimal approaches for
      managing women who have HR-HPV with normal cervical cytology (NCC) particularly
      in settings of HIV infection. METHODS: Between May 2012 and June 2013 we
      conducted a colposcopic assessment of HIV-infected women with prior (NCC) and
      known HR-HPV status to compare cervical abnormalities in women with and without
      HR-HPV. Colposcopic examinations were done at the Operation Stop Cervical Cancer
      (OSCC) unit of the Jos University Teaching Hospital (JUTH), Jos, Nigeria.
      Abnormal colposcopic finding (ACF) was defined as areas of aceto-white epithelium
      involving the squamo-coulumnar junction, areas of punctation, mosaic pattern or
      atypical vessels. We compared proportions of ACF as well as histologic grades of
      cervical intra-epithelial neoplasia (CIN) in women with or without HR-HPV.
      Statistical analysis was done on STATA. RESULTS: We conducted colposcopic
      examinations in 78 out of 89 (86.5%) eligible women. The mean age of the cohort
      was 32.4 years (SD +/-4.6) with a median 32 years (IQR 29-36). After a mean
      follow up time of 20.1 months from the initial cervical pap cytology and HR-HPV
      testing, we found 12 of 78 (15.4%) women with ACF. The odds for an ACF was
      statistically higher [OR = 4.0 (95% CI: 1.1-14.7)] in women with HR-HPV compared
      to those without. Of the twelve women with ACF, subsequent histologic examination
      of colposcopically directed cervical biopsies confirmed CIN 1 in 4 cases (33.3%),
      CIN 2 in 1 case (8.3%), CIN 3 in 2 cases (16.7%), carcinoma-in-situ (CIS) in 2
      cases (16.7%), and normal cervix in 3 (25.0%). Overall, the proportion of women
      detected with any grade of CIN was 11.5% (9/78) and 6.4% (5/78) were CIN 2 or
      greater lesion (CIN2+). CONCLUSION: HIV-infected women with NCC and HR-HPV had a
      four-fold higher likelihood for an ACF. The practice of early colposcopic
      examination of HIV-infected women with prior NCC and HR-HPV may increase early
      detection of higher grade CIN and CIS cancer stages in our setting.

PMID- 25395988
TI  - Schematic and realistic biological motion identification in children with high
      functioning autism spectrum disorder.
AB  - Research investigating biological motion perception in children with ASD has
      revealed conflicting findings concerning whether impairments in biological motion
      perception exist. The current study investigated how children with high
      functioning ASD (HF-ASD) performed on two tasks of biological motion
      identification: a novel schematic motion identification task and a point-light
      biological motion identification task. Twenty-two HFASD children were matched
      with 21 TD children on gender, non-verbal mental, and chronological, age (M years
      = 6.72). On both tasks, HF-ASD children performed with similar accuracy as TD
      children. Across groups, children performed better on animate than on inanimate
      trials of both tasks. These findings suggest that HF-ASD children's
      identification of both realistic and schematic biological motion identification
      is unimpaired.

PMID- 25395989
TI  - Recruitment dynamics in adaptive social networks.
AB  - We model recruitment in adaptive social networks in the presence of birth and
      death processes. Recruitment is characterized by nodes changing their status to
      that of the recruiting class as a result of contact with recruiting nodes. Only a
      susceptible subset of nodes can be recruited. The recruiting individuals may
      adapt their connections in order to improve recruitment capabilities, thus
      changing the network structure adaptively. We derive a mean field theory to
      predict the dependence of the growth threshold of the recruiting class on the
      adaptation parameter. Furthermore, we investigate the effect of adaptation on the
      recruitment level, as well as on network topology. The theoretical predictions
      are compared with direct simulations of the full system. We identify two
      parameter regimes with qualitatively different bifurcation diagrams depending on
      whether nodes become susceptible frequently (multiple times in their lifetime) or
      rarely (much less than once per lifetime).

PMID- 25395990
TI  - Uterine tumor resembling ovarian sex cord tumor (UTROSCT), case report with
      literature review.
AB  - INTRODUCTION: Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are
      uterine neoplasms of unknown histiogenesis which show near complete
      differentiation towards ovarian sex cord elements and are postulated to arise
      from pluripotential uterine mesenchymal cells or endometrial stromal cells with
      secondary sex cord differentiation. CASE PRESENTATION: A 48 year old post
      menopausal women presented with abnormal uterine bleeding for which she underwent
      total abdominal hysterectomy with bilateral salpingo-ophorectomy. Gross
      examination revealed a gelatinous grayish white tumor confined to the myometrium,
      7 cm in maximum dimention. Microscopic examination revealed monomorphic round to
      oval tumor cells in anastomosing cords and trabeculae with myxoid background.
      Immunohistochemically, tumor cells showed diffuse positivity for vimentin, CD99
      and S100, while focal positivity was seen with pancytokeratin immunostain. The
      case was diagnosed as UTROSCT. No evidence of metastasis was found on systemic
      clinical and radiologic workup. CONCLUSION: UTROSCT are rare uterine tumors which
      can be diagnosed with certainty on morphologic and immunohistochemical grounds.
      It is important to recognize these tumors as they behave differently from
      endometrial stromal tumors with sex cord like elements (ESTSCLE).

PMID- 25395991
TI  - Chd1 co-localizes with early transcription elongation factors independently of
      H3K36 methylation and releases stalled RNA polymerase II at introns.
AB  - BACKGROUND: Chromatin consists of ordered nucleosomal arrays that are controlled
      by highly conserved adenosine triphosphate (ATP)-dependent chromatin remodeling
      complexes. One such remodeler, chromodomain helicase DNA binding protein 1
      (Chd1), is believed to play an integral role in nucleosomal organization, as the
      loss of Chd1 is known to disrupt chromatin. However, the specificity and basis
      for the functional and physical localization of Chd1 on chromatin remains largely
      unknown. RESULTS: Using genome-wide approaches, we found that the loss of Chd1
      significantly disrupted nucleosome arrays within the gene bodies of highly
      transcribed genes. We also found that Chd1 is physically recruited to gene
      bodies, and that its occupancy specifically corresponds to that of the early
      elongating form of RNA polymerase, RNAPII Ser 5-P. Conversely, RNAPII Ser 5-P
      occupancy was affected by the loss of Chd1, suggesting that Chd1 is associated
      with early transcription elongation. Surprisingly, the occupancy of RNAPII Ser 5
      P was affected by the loss of Chd1 specifically at intron-containing genes.
      Nucleosome turnover was also affected at these sites in the absence of Chd1. We
      also found that deletion of the histone methyltransferase for H3K36 (SET2) did
      not affect either Chd1 occupancy or nucleosome organization genome-wide.
      CONCLUSIONS: Chd1 is specifically recruited onto the gene bodies of highly
      transcribed genes in an elongation-dependent but H3K36me3-independent manner.
      Chd1 co-localizes with the early elongating form of RNA polymerase, and affects
      the occupancy of RNAPII only at genes containing introns, suggesting a role in
      relieving splicing-related pausing of RNAPII.

PMID- 25395992
TI  - Targeting the estrogen pathway for the treatment and prevention of lung cancer.
AB  - The estrogen signaling pathway is involved in the biology of non-small-cell lung
      cancer and represents a novel therapeutic target for lung cancer. This is
      supported by epidemiological evidence, preclinical studies and recent data from
      clinical trials. Antiestrogens and inhibitors of estrogen synthesis have been
      shown to inhibit lung tumor growth as well as prevent lung tumorigenesis in
      preclinical models both in vitro and in vivo. Two clinical trials testing the
      effectiveness of hormonal strategies in advanced non-small-cell lung cancer have
      recently been completed with promising results. Future work in this field should
      focus on identification of patients that would benefit from hormone modulators so
      that they can be used earlier in the course of disease or for chemoprevention.

PMID- 25395993
TI  - The effect of perturbations on resistance to sliding in second-order moments
      comparing two different bracket types.
AB  - Orthodontic literature has shown all ligation methods to behave similarly in the
      clinical situation; however, the reasoning behind this still requires further
      investigation. A novel frictional device able to measure forces at the level of
      the bracket along with a custom perturbation device was used to investigate the
      effect of perturbations on resistance to sliding (RS) using conventional and
      passive ligated brackets. 150 3M Victory Series twins (0.022 slot) and 150 Damon
      Q brackets (0.022 slot) were tested using an 0.018 x 0.025 stainless steel wire
      for RS. There were 5 test groups consisting of equal numbers (n=30) representing
      combinations of high and low amplitude and frequency of perturbations along with
      a control. Second order angulation tested ranged from 0 to 6 degrees. Results for
      conventional brackets in the presence of perturbations at 0 degrees showed there
      was a statistically significant reduction (P<0.001) in RS when compared to
      controls. At 6 degrees, this difference (P<0.001) was seen in both high
      perturbation groups and one of the low perturbation groups. For passive ligated
      brackets, no statistically significant difference between groups was seen at 0
      degrees. However, at 6 degrees high perturbation groups both resulted in
      statistically significant (P<0.001) reductions in RS when compared to controls.
      From this study it was concluded that passive ligated brackets have a lower RS
      when compared to conventional ligated brackets under all test conditions and
      angulations. Also, amplitude of perturbations has a larger role than frequency in
      reduction of RS values. 

PMID- 25395994
TI  - Transcriptional repression is epigenetically marked by H3K9 methylation during
      SV40 replication.
AB  - BACKGROUND: We have recently shown that T-antigen binding to Site I results in
      the replication-dependent introduction of H3K9me1 into SV40 chromatin late in
      infection. Since H3K9me2 and H3K9me3 are also present late in infection, we
      determined whether their presence was also related to the status of ongoing
      transcription and replication. Transcription was either inhibited with 5,6
      dichloro-1-beta-D-ribofuranosylbenzimidizole (DRB) or stimulated with sodium
      butyrate and the effects on histone modifications early and late in infection
      determined. The role of DNA replication was determined by concomitant inhibition
      of replication with aphidicolin. RESULTS: We observed that H3K9me2/me3 was
      specifically introduced when transcription was inhibited during active
      replication. The introduction of H3K9me2/me3 that occurred when transcription was
      inhibited was partially blocked when replication was also inhibited. The
      introduction of H3K9me2/me3 did not require the presence of H3K9me1 since similar
      results were obtained with the mutant cs1085 whose chromatin contains very little
      H3K9me1. CONCLUSIONS: Our data suggest that methylation of H3K9 can occur either
      as a consequence of a specific repressive event such as T-antigen binding to Site
      I or as a result of a general repression of transcription in the presence of
      active replication. The results suggest that the nonproductive generation of
      transcription complexes as occurs following DRB treatment may be recognized by a
      'proof reading' mechanism, which leads to the specific introduction of H3K9me2
      and H3K9me3.

PMID- 25395995
TI  - Pharmacology and Toxicology of Nav1.5-Class 1 anti-arrhythmic drugs.
AB  - Although cardiac sodium channel blocking drugs can exert antiarrhythmic actions,
      they can also provoke life-threatening arrhythmias through a variety of
      mechanisms. This review addresses the way in which drugs interact with the
      channel, and how these effects translate to clinical beneficial or detrimental
      effects. A further understanding of the details of channel function and of drug
      channel interactions may lead to the development of safer and more effective
      antiarrhythmic therapies.

PMID- 25395997
TI  - Bridging Ayurveda with evidence-based scientific approaches in medicine.
AB  - This article reviews contemporary approaches for bridging Ayurveda with evidence
      based medicine. In doing so, the author presents a pragmatic assessment of
      quality, methodology and extent of scientific research in Ayurvedic medicine. The
      article discusses the meaning of evidence and indicates the need to adopt
      epistemologically sensitive methods and rigorous experimentation using modern
      science. The author critically analyzes the status of Ayurvedic medicine based on
      personal observations, peer interactions and published research. This review
      article concludes that traditional knowledge systems like Ayurveda and modern
      scientific evidence-based medicine should be integrated. The author advocates
      that Ayurvedic researchers should develop strategic collaborations with
      innovative initiatives like 'Horizon 2020' involving predictive, preventive and
      personalized medicine (PPPM). 

PMID- 25395996
TI  - Diseases caused by mutations in Nav1.5 interacting proteins.
AB  - Sodium current in the heart flows principally through the pore protein NaV1.5,
      which is part of a complex of interacting proteins that serve both to target and
      localize the complex in the membrane, and to modulate function by such post
      translational modifications as phosphorylation and nitrosylation. Multiple
      mutations in seven different NaV1.5 interacting proteins have been associated
      with dysfunctional sodium current and inherited cardiac diseases, including long
      QT syndrome, Brugada syndrome, atrial fibrillation, and cardiomyopathy, as well
      as sudden infant death syndrome (SIDS). Mutations in as yet unidentified
      interacting proteins may account for cardiac disease for which a genetic basis
      has not yet been established. Characterizing the mechanisms by which these
      mutations cause disease may give insight into etiologies and treatments of more
      common acquired cardiac disease, such as ischemia and heart failure.

PMID- 25395998
TI  - Iron deficiency anaemia in patients with inflammatory bowel disease: National
      Consultant for Gastroenterology Working Group Recommendations.
AB  - Anaemia is a common complication associated with inflammatory bowel diseases
      (Crohn's disease and ulcerative colitis). It substantially impairs quality of
      life, makes therapy more complicated, and increases costs of treatment. It seems
      that anaemia therapy is suboptimal in this group of patients in the Polish
      population. The recommendations presented below provide iron deficiency anaemia
      management clues in patients with inflammatory bowel disease. 

PMID- 25395999
TI  - Diagnosis of Hirschsprung's disease with particular emphasis on histopathology. A
      systematic review of current literature.
AB  - Hirschsprung's disease (HD) is a disorder that involves several medical
      specialties such as paediatric gastroenterology, paediatric surgery, and
      pathology. Hirschsprung's disease is a congenital bowel innervation disorder
      characterised by the absence of ganglion cells in myenteric (Auerbach) and
      submucosal (Meissner) plexus in the distal colon in its classical form. Rapid and
      accurate diagnosis of HD is a key element in further treatment patterns. The
      efficiency of different diagnostic methods used in HD patients may vary. Using
      one limited diagnostic procedure can lead to as much as a few per cent of
      overlooked cases. In recent years, rectal biopsy was recognised as an important
      diagnostic tool that allows for a definitive HD diagnosis with an accuracy of 95%
      of cases. A correct diagnosis depends on the localisation of the biopsied sample,
      its representativeness, the number of specimens, and proper interpretation of
      microscopic studies supported by histochemical and immunohistochemical methods.
      When several methods are used and all diagnostic criteria are used, the
      diagnostic sensitivity can almost eliminate cases of undiagnosed patients. 

PMID- 25396000
TI  - Non-medical costs of colonoscopy.
AB  - Colorectal cancer is one of the most common malignancies in Europe and North
      America. Colonoscopy done every 10 years beginning at age 50 is the preferred
      method of screening. In Poland and some other countries examinations are offered
      to subjects free of charge. However, as well as direct medical costs there are
      direct non-medical costs, which include the cost of transportation and costs
      related to caregivers' time, and indirect costs, which are costs related to
      patients' time. These costs essentially augment the total societal costs of
      colonoscopy. 

PMID- 25396001
TI  - Alterations in programmed cell death mechanism and their role in the pathogenesis
      of inflammatory bowel diseases.
AB  - Apoptosis plays an essential role in both physiology and pathology. In the
      pathogenesis of inflammatory bowel diseases, disturbances of apoptosis also play
      an important role. Inflammatory cells (for example lymphocytes, granulocytes) in
      the gut wall are resistant to apoptotic stimuli and they accumulate there causing
      tissue damage. On the other hand, apoptotic elimination of the enterocytes is
      enhanced, which leads to the impairment of the gut barrier. The exact mechanisms
      of these phenomena are still poorly understood and they are still under
      investigation. The present paper summarises current knowledge in terms of the
      role of alterations of programmed cell death in the pathogenesis of inflammatory
      bowel diseases. 

PMID- 25396002
TI  - Lack of association between human papillomavirus infection and colorectal cancer.
AB  - INTRODUCTION: Colorectal cancer is the third leading cause of cancer-related
      deaths worldwide, with nearly one million new cases identified annually.
      Different factors might cause colorectal cancer, one of the most prevalent
      cancers among both men and women. Viral aetiology in cancerous malignancies is a
      very important issue and so far a number of viral strains have been identified as
      tumour oncogene viruses. Viral infections, such as human papillomavirus (HPV),
      have recently been suggested as a risk factor for colorectal cancer. However, the
      aetiology of the disease is still unknown. AIM: To assessed the association
      between HPV infection and colorectal cancer. MATERIAL AND METHODS: In this study,
      50 cancer tissue samples and 50 samples without colon cancer were studied in
      order to identify HPV through polymerase chain reaction (PCR). Of 42
      adenocarcinomas, 10 were well differentiated, 30 moderated differentiated, and 2
      were poorly differentiated. DNA extraction was verified by beta globin gene
      amplification; specific PCR was carried out based on HPV L1 consensus primers
      MY09/MY11. RESULTS: HPV DNA was not identified in any of the normal,
      adenocarcinoma, or adenoma samples. CONCLUSIONS: In contrast with previous
      studies, the current research failed to establish a relationship between HPV
      infection and the incidence of colon cancer. Considering the existing
      inconsistencies, it is recommended that further studies be conducted with larger
      sample size.

PMID- 25396003
TI  - Management of traveller's diarrhoea with a combination of sodium butyrate,
      organic acids, and A-300 silicon dioxide.
AB  - INTRODUCTION: Traveller's diarrhoea (TD), defined by UNICEF/WHO as three or more
      unformed stools with or without other symptoms, imposes a considerable burden on
      travellers from developed countries. Various efforts have focused on decreasing
      the prevalence and severity of this condition. AIM: To assess the efficacy of a
      combination of sodium butyrate, organic acids, and A-300 silicon dioxide in
      treatment providing symptomatic relief of TD. MATERIAL AND METHODS: The study was
      conducted in accordance with a protocol presented to the Bioethical committee of
      Poznan University of Medical Sciences. A total of 278 patients travelling to
      countries with higher risk of diarrhoea for at least 10 days were divided into a
      study arm being administered, in case of TD, a combination of sodium butyrate,
      organic acids, and A-300 silicon dioxide (n = 139) and a placebo arm (n = 139)
      with placebo administration. RESULTS: Forty-seven patients completed the study
      (22 in the study arm and 25 in the placebo arm). The diarrhoea occurrence after
      initiation of treatment at first symptoms was significantly lower in the study
      arm as compared to the placebo arm (9% vs. 36%, p = 0.041). Also, subjects from
      the study arm more frequently reported that the regimen administered had been
      efficient for their symptoms in comparison to the placebo arm (72.7% vs. 32%, p =
      0.008). No adverse effects of the administered medication were noted during the
      study. CONCLUSIONS: Sodium butyrate, organic acids, and A-300 silicon dioxide can
      be successful in decreasing symptoms of TD. Because of its efficacy and lack of
      observed side effects it has a strong potential in the treatment of patients with
      TD.

PMID- 25396004
TI  - Comparing methods of ileostomy closure constructed in colorectal surgery in
      Turkey.
AB  - INTRODUCTION: Stoma construction is a life saver method for emergent and elective
      operations in colorectal surgery. However, they are associated with high rates of
      morbidity and mortality. AIM: To compare the operative findings, early
      postoperative complications, and costs of stapled and hand-sewn closures in loop
      ileostomies that are constructed in emergent and elective colorectal surgery.
      MATERIAL AND METHODS: The data of 68 patients requiring loop ileostomies during
      colorectal surgery were retrospectively evaluated. SPSS (version 20) was used for
      data analysis. RESULTS: The study group consisted of 44 men and 24 women with a
      mean age of 55.5 years. The ileostomy closures were performed with hand-sewn
      method in 36 patients (group 1) and stapled method in 32 patients (group 2). The
      mean operation time was 75.4 min in group 1 and 46.7 min in group 2 (p < 0.001).
      Early postoperative complications were wound infection (8.8%), small bowel
      obstruction (6.06%), and anastomotic leakage (2.9%). Total costs, flatulence and
      faeces outlet time, oral feeding starting time, time of hospital stay, and early
      postoperative complications were lower in the stapled group. CONCLUSIONS:
      Morbidity and mortality rates of stoma construction and its closure are still
      considerable. Lower anastomotic leakage rate, complication rate, and costs and
      shorter operative times in the stapled group make this method preferable.

PMID- 25396005
TI  - Risk factors for gastroesophageal reflux disease: the role of diet.
AB  - INTRODUCTION: Nutrition can contribute to the development of gastroesophageal
      reflux disease (GERD). The relevant studies often provide contradictory results.
      AIM: To determine GERD risk factors associated with dietary habits. MATERIAL AND
      METHODS: A total of 513 subjects were included. The study group consisted of
      adults with a recent clinically confirmed diagnosis of GERD, and the control
      group were healthy adults. The research tool was a proprietary questionnaire.
      Risk factors were evaluated by logistic regression models. RESULTS: An
      association was found between the severity of typical GERD symptoms and a certain
      diet (p < 0.001). The symptoms were experienced more often after fatty, fried,
      sour, or spicy food and sweets. The univariate logistic regression analysis
      showed the following risk factors: eating 1-2 meals per day (OR = 3.50, 95% CI:
      1.75-6.98), everyday consumption of peppermint tea (OR = 2.00, 95% CI: 1.14
      3.50), and eating one, big meal in the evening instead of dinner and supper (OR =
      1.80, 95% CI: 1.05-3.11). The multivariate analysis confirmed that frequent
      peppermint tea consumption was a risk factor (OR = 2.00, 95% CI: 1.08-3.70).
      CONCLUSIONS: Taking into consideration the results of this study, it seems that
      patients should be recommended to eat more than three meals a day and eat dinner
      and supper at appropriate times instead of one, big meal in the evening. The role
      of frequent peppermint tea consumption in GERD development requires further
      studies.

PMID- 25396006
TI  - Heterotopic gastric mucosa of upper oesophagus: evaluation of 12 cases during
      gastroscopic examination.
AB  - INTRODUCTION: Oesophageal heterotopic gastric mucosa mostly presents in the upper
      part of the oesophagus. It is commonly under-diagnosed because of its
      localisation. AIM: To expose the association between heterotopic gastric mucosa
      and endoscopic features of the upper gastrointestinal tract. MATERIAL AND
      METHODS: A total of 1860 upper endoscopic examinations performed between January
      2012 and July 2013 were analysed retrospectively. Endoscopic features and
      histological examinations of 12 heterotopic gastric mucosa (HGM) of the upper
      oesophagus were documented and evaluated retrospectively. RESULTS: There were 7
      (58%) male and 5 (42%) female patients aged between 22 and 80 years with a mean
      age of 43.2 years. Heterotopic gastric mucosa was present in 12 (0.6%) of all
      patients. We were able to perform biopsy for histopathological observation on 8
      (66%) of the 12 patients in which HGM was seen during endoscopy. Five (42%)
      patients with heterotopic gastric mucosa had oesophagitis. Los Angeles Grade A
      oesophagitis was found in all patients, and histologically proven Barrett's
      oesophagus was detected in only one patient. CONCLUSIONS: When a patient has
      ongoing dyspeptic complaints and reflux symptoms despite the treatment, one
      should be careful about possible HGM during upper gastrointestinal endoscopy. The
      point to be taken into consideration for patients who have metaplasia or
      dysplasia within HGM may need to be considered for surveillance.

PMID- 25396007
TI  - Ferroportin-related haemochromatosis associated with novel Y64H mutation of the
      SCL40A1 gene.
AB  - In this paper we described the first Polish patient with ferroportin disease.
      Hereditary haemochromatosis (HH) is a condition associated with universal iron
      overload, and it is divided into four types, according to the Online Mendelian
      Inheritance in Man (OMIM) database. Ferroportin disease represented a rare type
      of HH, with autosomal dominant trait of inheritance. In our patient we detected a
      novel mutation in the ferroportin gene, with non-classical phenotype. 

PMID- 25396008
TI  - Neurofibroma of the stomach without Recklinghausen's disease: a case report.
AB  - Neurofibromas of the stomach can occur in the course of Recklinghausen's disease.
      Sporadic gastric neurofibroma appears rarely. This tumour may look like an ulcer
      and can be a cause of abdominal pain, nausea, and bleeding from the
      gastrointestinal tract. We reported a 61-year-old women complaining of
      stomachache for several months. Gastroscopy revealed a tumour with ulceration in
      the prepyloric part of the stomach. Helicobacter pylori infection was also
      present. Helicobacter pylori eradication and prolonged treatment of proton pump
      inhibitors did not decrease the ailments or the size of the tumour. It was not
      possible to determine the nature and origin of the tumour by carrying out
      examinations such as endoscopic ultrasound and computed tomography of the
      abdomen. Only after surgery and histopathological examination with
      immunohistochemistry was this tumour identified as a neurofibroma. In order to
      differentiate the tumour the following immunohistochemical examinations were
      carried out: CD34 (slightly +), CD117 (-), S-100 (+), desmin (-), NSE (+), GFAP (
      ), SMA (-), bc12 (-), CD99 (-), ALK1 (-), and MiB (1-1.5%). In such cases
      excision of the tumour is the preferred treatment. 

PMID- 25396009
TI  - Giant sigmoid diverticulum.
AB  - Giant sigmoid diverticuli are uncommon and usually seen in association with
      multiple colonic diverticuli. A solitary diverticulum in an otherwise normal
      colon is very rare. Mostly asymptomatic, excision of giant sigmoid diverticuli is
      advised to prevent complications. 

PMID- 25396010
TI  - [Pseudo-Meigs syndrome: report of a case].

PMID- 25396011
TI  - Application of pediatric index of mortality version 2: score in pediatric
      intensive care unit in an African developing country.
AB  - INTRODUCTION: Outcome of patients admitted to PICU can be evaluated by many
      illness severity scoring systems. This prospective observational study evaluated
      the outcome of patients admitted to PICU in Fayoum University hospital of a
      developing country using the pediatric index of mortality version 2 scoring
      system. METHODS: All patients included in this study were subjected to data
      collection including demographics, diagnoses at admission, duration of ICU stay
      (DOS), pediatric index of mortality version 2 (PIM2) score and hospital outcome.
      The ratio of observed to predicted mortality (standardized mortality ratio (SMR))
      was calculated for the set of patients. RESULTS: The study included 205 patients.
      The main causes of admission were respiratory, cardiovascular and neurological
      illnesses. Patients stay in ICU ranged from 1 - 45 days with a median 6
      (interquartile range (IQ): 3-9) days. Discriminatory function of PIM2 scoring
      system was acceptable with the area under the ROC curve 0.76 (95%CI: 0.60-0.91).
      PIM2 calibrated well using Hosmer Lemeshow analysis (H-L X2= 1.410, df= 8,
      p=0.9). The mean predicted mortality was 5.6 (95% CI: 3.43 - 7.91) and the
      observed mortality was 8.8% giving a SMR 1.55. CONCLUSION: PIM2 scoring system
      show adequate discriminatory function and well calibrated for the case mix of
      patients in PICU of Fayoum, Egypt. It can be used as beneficial tool for
      evaluation of risk adjusted mortality. Further larger scale studies in
      cooperation with other Egyptian universities and neighboring countries can
      improve the performance of our PICUs and critical care services.

PMID- 25396012
TI  - Relationship between multiple drug resistance and biofilm formation in
      Staphylococcus aureus isolated from medical and non-medical personnel in Yaounde,
      Cameroon.
AB  - INTRODUCTION: Monitoring the prevalence of nasal carriage of multiple drug
      resistance (MDR) Staphylococcus aureus (SA) strains in hospital personnel is
      essential. These strains when transmitted from hospital personnel to patients
      with already weakened immune states or in-built medical devices, may limit the
      latter's treatment options. This study aimed at assessing the potential exposure
      of patients to these MDR SA in a resource-limited hospital setting by assessing
      the prevalence and relationship between antimicrobial susceptibility and biofilm
      forming capacity of SA isolates from hospital personnel. METHODS: A total of 59
      bacteria isolates phenotypically identified as Staphylococcus aureus obtained
      from medical (39) and non-medical personnel (20) in Yaounde were used in the
      study. Multiple drug resistance defined as resistance to four or more of twelve
      locally used antibiotics were determined by Kirby Bauer disc diffusion technique
      whereas quantification of biofilm production was by the microtitre plate method.
      RESULTS: Among the 59 SA isolates, the prevalence of MDR was 50.9%. Among medical
      personnel 48.7% had MDR as against 55.9% for non-medical personnel (p
      value=0.648). The overall percentage of weak biofilm producers was 35.6%.
      Although the prevalence of weak biofilm formers was higher in isolates from non
      medical personnel (40%) than medical personnel (33.3%) the difference was not
      statistically significant (p-value= 0.246). Slightly less than half (42.9%) of
      the weak biofilm producers were MDR. CONCLUSION: Considering the high rates of
      MDR and that slightly less than half of biofilm formers were MDR, these trends
      need to be monitored regularly among hospital personnel in Yaounde.

PMID- 25396013
TI  - Predictors to parental knowledge about childhood immunisation/EPI vaccines in two
      health districts in Cameroon prior to the introduction of 13-valent Pneumococcal
      Conjugate Vaccines (PCV-13).
AB  - INTRODUCTION: Pneumonia is vaccine-preventable, but the increasing death toll
      resulting from the disease in Sub-Saharan Africa is alarming. Several factors
      account for vaccine failing to reach every child, besides incomplete vaccine
      coverage. Most of these include the perceptions of parents/guardians and
      healthcare providers. Previous studies on the introduction of new vaccines have
      focused on experimental trials, coverage figures and vaccine efficacy in
      developed countries. Little is known on the factors which may hinder the
      implementation process despite the huge challenges this may encounter in
      developing countries. This study described the knowledge, attitude and practices
      (KAP) of parents/guardians on pneumonia and immunisations/EPI vaccines; identify
      predictive parental socio-economic/demographic characteristics that of good
      knowledge on pneumonia infections, routine EPI vaccines and the PCV-13. Finally,
      the study described health center personnel perceptions about immunisations.
      METHODS: The WHO's immunisation coverage cluster survey design was used,
      involving parents/guardians (n = 205) of children aged 0-59 months and health
      centre personnel (n = 13) directly concerned with vaccination activities between
      July-September 2010 in two health districts in Yaounde, Cameroon. Descriptive
      statistics and multivariate logistic models were used to analyse the
      parental/guardian data while the health personnel data was only analysed
      descriptively using SPSS version 17.0. RESULTS: Only 19% of the parents/guardians
      were aware of the availability of the PCV-13. Logistic modelling identified
      important associations between parental socio-economic/demographic factors and
      good knowledge on pneumonia disease burden and prevention. CONCLUSION: According
      to parents/guardians a short and clear message on the dangers of pneumonia and
      the need for prevention provided to parents/guardians during sensitisation/out
      reach campaigns and use of social network avenues would be primordial, if the PCV
      13 is to reach every child.

PMID- 25396014
TI  - [Current status of atypical mycobacterial infections in Burkina Faso: results of
      a regional survey].

PMID- 25396016
TI  - [Scrotal elephantiasis revealing prostate cancer].

PMID- 25396015
TI  - Human papillomavirus (HPV) testing on self-collected specimens: perceptions among
      HIV positive women attending rural and urban clinics in South Africa.
AB  - INTRODUCTION: Cervical cancer is the most common cancer among women in Sub
      Saharan Africa. Cervical cancer is treatable if detected timeously, yet only 20%
      of South African women have ever been for a Pap smear in their lifetime due to
      limited access to screening, transport or child care responsibilities. OBJECTIVE:
      To evaluate the acceptability of self-collection for cervical cancer screening.
      We aimed to identify which self-collection device women prefer and if they would
      consider using them for routine cervical cancer screening. METHODS: HIV-positive
      women (>18 years) from urban and rural HIV clinics were interviewed following an
      education session on HIV, human papillomavirus (HPV) and cervical cancer.
      Participants were shown three self-collection devices; (i) an Evalyn cervical
      brush, (ii) a Delphilavager and (iii) a tampon-like plastic wand before
      completing a short questionnaire. RESULTS: A total of 106 women from the urban (n
      = 52) and rural (n = 54) clinic were interviewed. Overall 51% of women preferred
      the cervical brush, while fewer women preferred the tampon-like plastic wand
      (31%) or lavage sampler (18%). More than 75% of women from the rural site
      preferred the cervical brush, compared to 22% from the urban site (p < 0.001).
      Women from the urban clinic preferred the tampon-like plastic wand (45%) and then
      the lavage sampler (33%), as compared to women from the rural clinic (19% and 4%,
      respectively). CONCLUSION: Women from urban or rural settings had different
      preferences for the various self-collection devices. Patient self-collection with
      HPV testing may be an acceptable way to improve coverage to cervical cancer
      screening in high risk HIV-seropositive women.

PMID- 25396017
TI  - Incidence of childhood cancer in Namibia: the need for registries in Africa.
AB  - INTRODUCTION: Childhood cancer is rare and comprises only 1% of all cancers. The
      current incidence of childhood cancer in Namibia, as in many other African
      countries, is not known. The aim of this research was to assess the paediatric
      cancer incidence between 2003-2010 at Windhoek Central Hospital, the only
      pediatric oncology-referring centre in Namibia and to compare with the previous
      calculated incidence in the country 20 years ago. METHODS: A retrospective,
      descriptive review of the paediatric oncology cases presenting to Windhoek
      Central Hospital between 2003 and 2010 was undertaken, and data regarding age,
      sex, cancer type, area of residence were extrapolated. In this study due to the
      appearance of the HIV epidemic, an HIV incidence was also calculated. RESULTS:
      The incidence rate of all paediatric recorded cancers was 29.4 per million.
      Leukaemias (22.5%) and retinoblastomas (16.2%) were the most common tumours, with
      renal tumours, soft tissue sarcomas and lymphomas following in frequency. HIV
      incidence of children with malignancy was 6.8%. CONCLUSION: The incidence rates
      of cancers in this study are remarkably lower compared to a similar study done in
      the country 20 years ago. Many cancers are still not diagnosed or reported, and
      others are not treated in the country. The institution of a "twinning programme"
      between the paediatric haematological/oncological departments in Windhoek and
      Tygerberg Hospital in Cape Town, South Africa, will contribute to improvement of
      childhood cancer cases. This twinning programme includes the formation of a
      cancer registry.

PMID- 25396018
TI  - Cord blood full blood count parameters in Lagos, Nigeria.
AB  - INTRODUCTION: Full blood count (FBC), one of the most frequently requested for
      laboratory investigations, is a simple, fast and cheap test and is a reliable
      indicator of health. Due to its usefulness in the assessment of health status of
      individuals, its parameters in cord blood, a major source of haemopoietic stem
      cell transplantation and an ideal source for laboratory investigations for
      newborns were determined to provide a useful guide to local neonatologists and
      stem cell transplant physicians. METHODS: Three millilitres of umbilical cord
      blood was collected from 130 normal birth weight newborns (69 males and 61
      females) whose cord were clamped immediately after delivery, at a teaching
      hospital in Lagos, Nigeria and full blood count parameters were determined using
      Sysmex autoanalyzer, model KX-21N. Consented mothers of the newborns were
      selected based on, age between 18 and 45 years; uneventful pregnancy and delivery
      and haemoglobin (Hb) concentration >= 10 g/dL. RESULTS: There were no statistical
      gender differences in the mean values of Hb concentrations (M = 13.27 +/-1.60
      g/dL; F = 13.32+/-1.61g/dL; p = 0.93), total white cell count (M = 3.16+/-5.43 *
      10(9)/L; F = 13.07+/-4.98 * 10(9)/L; p= 0.92), platelet count (M= 223.64+/- 64.21
      * 10(9)/L; F = 226.69+/-80.83 * 10(9)/L; p = 0.81) and other parameters.
      CONCLUSION: Mean values of full blood count parameters obtained in this study are
      comparable to reports from other studies in developing countries and could be a
      useful guide for neonatologists and stem cell transplant physicians in our
      geographical location.

PMID- 25396019
TI  - [Type 2 diabetic patients with hypertension: do they prefer treating diabetes or
      hypertension?].

PMID- 25396020
TI  - [Post-traumatic iris cyst in a child].

PMID- 25396021
TI  - Congenital giant epulis obstructing oral cavity: newborn emergency.
AB  - The congenital epulis is a benign congenital granular cell tumor arising most
      often of the alveolar ridge of the jawbone. When giant, it is source of digestive
      discomfort disabling feeding. We report the case of a newborn female, vaginal
      delivery, presented with a giant intraoral tumor. Tumor obstructing the mouth of
      the newborn and prevent the attachment and feeding. The treatment consisted of
      excision of the tumor under general anesthesia. The histology of the tumor was
      revealed that it was an epulis. 

PMID- 25396022
TI  - [Dissection of the descending thoracic aorta and abdominal aorta in Takayasu's
      arteritis: report of a case].

PMID- 25396023
TI  - Sero-prevalence and factors associated with Hepatitis B and C co-infection in
      pregnant Nigerian women living with HIV infection.
AB  - INTRODUCTION: Perinatal and horizontal transmission of Hepatitis B occur in areas
      of high endemicity as most infections are acquired in the first 5 years of life.
      Unless Hepatitis B and C infected pregnant women identified, and appropriate
      treatment provided, children born to these women are at high risk of chronic
      Hepatitis B (and C) virus infection. The objecive of this study was to determined
      the prevalence and the factors associated with Hepatitis B and C Virus infection
      in pregnant HIV positive Nigerians. METHODS: A cross sectional study among HIV
      Positive pregnant women seen at a large PMTCT clinic in Lagos Nigeria. The women
      were screened for Hepatitis B and C Virus infection at enrollment. HIV viral
      load, CD4 count, liver transaminases and hemoglobin levels were also determined.
      Data were managed with SPSS for windows version. Ethical approval was obtained
      from the Institutions Ethical Review Board. RESULTS: Of the 2391 studied
      subjects, 101(4.2%) and 37(1.5%) respectively were seropositive for Hepatitis B
      and C Virus infection. Twowomen (0. 08%) had triple infections. blood
      transfusion, (cOR: 2.3; 95% CI:1.1-4.6), history of induced abortion (cOR:2.
      2;95% CI:1.3-3.6), and elevated baseline ALT (cOR:2. 2; 95%CI:2. 2;4.2) were
      significantly associated with HBV. History of induced abortion was the only
      factor found to be associated with HIV/ HCV (cOR: 1.9;95%CI:1. 3-3.9).
      CONCLUSION: Hepatitis B Virus infection (4.2%) is relatively common in our
      environment and associated with induced abortion, blood transfusion and elevated
      baseline transaminase. Hepatitis C Virus infection (1.5%) is less common and
      associated with only history of induced abortion.

PMID- 25396024
TI  - Tuberculosis in developing countries: conditions for successful use of a
      decentralized approach in a rural health district.
AB  - INTRODUCTION: This article reports the results and the lessons learned from
      implementing the decentralized approach to tuberculosis (TB) detection and
      treatment, embedded with Human Immunodeficiency Virus (HIV) co-infection in
      health district. The objective was to increase the TB screening indicators in the
      district using the common ways for offering care to patients in health district.
      METHODS: Conducted from August 2006 to July 2007, this large-scale intervention
      using Non-experimental study Designs has implemented a decentralized approach for
      fighting against TB in Orodara Health District (OHD), Burkina Faso. Pretest
      posttest design has been used for quantitative part using indicators in one hand,
      and postests-only design for the qualitative part in other hand. In the pretest
      posttest design, the TB indicators from years before 2006 (from 2002 to 2005)
      were used as earlier measurement observations allowing examining changes over
      time. The decentralized approach was incorporated into the annual planning of the
      OHD. For the quantitative study design, indicators used were those from National
      TB Program in Burkina Faso: TB detection rate, incidence density of TB per
      100,000 inhabitants per year, and HIV prevalence in incident TB cases with
      positive smears. Data entry and analysis employed Microsoft Access and Excel
      software. For the qualitative, in-depth interview was used in which a total of 16
      persons have been interviewed. Discussions were tape-recorded and transcribed
      verbatim for analysis using the computer-based qualitative software program named
      QSR NVIVO. RESULTS: There were a total of 99,259 outpatient visits during the
      study period: the7,345 patients (7.43%) presented with cough. Of the 7,345
      patient having cough, 503 cases (6.8%) were declared chronic coughing. These 503
      patients were screened for TB, including 35.59% whose coughing had lasted 10 to
      15 days. We observed an increase in a measured variable was observed. The TB
      detection rate and incidence-density rate based on positive smears were 16.11%
      (11.00% in 2005) and 10.42 per 100,000 inhabitants per year (6.88 per 100,000
      inhabitants in 2005), respectively. There were 29 patients positive for TB:
      41.37% of these had cough lasting 10 to 15 days, 10.34% were also positive for
      HIV, and 68.97% were from rural areas. Health workers and patients reported
      satisfaction with the intervention. It was found that implementing a
      decentralized approach to TB prevention in rural areas is plausible and effective
      under some conditions: considering that health district system is functional;
      carefully designing the intervention for TB case management; setting up and
      implementing of decentralized approach including strong monitoring; and taking
      into account the all financing, community and volunteer involvement, evaluation
      of the cost savings from integrating specific donor funding, and being supported
      by regional and central levels including National TB program. CONCLUSION: The
      study has shown that TB detection rate can be increased by implementing a
      decentralized approach to primary care. When carefully implemented, a
      decentralized approach is a suitable approach to TB and HIV prevention in rural
      and inaccessible settings.

PMID- 25396025
TI  - [Coronary surgery under cardiopulmonary bypass in patients with diabetes].

PMID- 25396026
TI  - Water pipe smoking: an emerging trend with detrimental consequences.

PMID- 25396027
TI  - Maternal mortality in Central Province, Kenya, 2009-2010.
AB  - INTRODUCTION: Maternal mortality for Kenya was 488/100,000 live births in 2009.
      Maternal mortality estimate for Central Province is unknown. We retrospectively
      reviewed data between 1st July 2009 and 30th June 2010 to estimate the hospital
      based maternal mortality ratio, characterize deaths by time, place and person and
      describe possible causes of deaths in Central province, Kenya. METHODS: We
      abstracted data using a standard form from maternal death notification and review
      forms and the district reproductive health reports. Data was entered and analyzed
      using Microsoft Excel. RESULTS: There were 89,512 live births and 111 deaths. The
      facility-based maternal mortality ratio was 124/100,000 live births. Seventy
      three (66%) deaths had been audited. Thirty seven (33%) were aged 25 to 34 years.
      The mean age was 31 years (+/-6). Thirty seven (33%) had a parity of less or
      equal to 2. Most case deaths (19%, n = 21) had attended 2 or less antenatal
      visits. The main gestation was below 37 weeks with 48% (n = 53). The main mode of
      delivery was vaginal (26%, n = 29). Majority (35%, n = 32) case deaths had
      delivered a live birth. Thirty seven (33%) mothers had been stable on admission.
      The main reason for admission was labor with 12% (n = 13). Thirty-eight (34%)
      died within 24 hours after admission. Majority (27%, n = 30) were admitted
      antepartum but 39% (n = 43) were postpartum at the time of death. Thirty-five
      (32%) died of hemorrhage and 8 (7%) Eclampsia. CONCLUSION: Maternal mortality is
      of public health importance in the region. Most deaths occurred within 24 hours
      after admission. Third delay was important. Bleeding and Eclampsia were the main
      causes of death. A third (34%) of notified deaths were not reviewed.

PMID- 25396028
TI  - [Toxic epidermal necrolysis induced by phenobarbital in a Rwandan child: report
      of a case].

PMID- 25396029
TI  - Advances in synthetic peptide immuno-regulatory epitopes.
AB  - Synthetic peptide immuno-regulatory epitopes (SPIRE) represent a new class of
      therapeutics for allergen immunotherapy that offer the potential to suppress the
      IgE-mediated allergic disease process through induction of T-cell tolerance.
      These synthetic T-cell-tolerizing peptides have been designed to induce
      immunologic tolerance via binding to MHC class II molecules on antigen presenting
      cells, with subsequent upregulation of regulatory T-cells. 

PMID- 25396030
TI  - Tailoring the Spectroscopic Properties of Semiconductor Nanowires via Surface
      Plasmon-Based Optical Engineering.
AB  - Semiconductor nanowires, due to their unique electronic, optical, and chemical
      properties, are firmly placed at the forefront of nanotechnology research. The
      rich physics of semiconductor nanowire optics arises due to the enhanced light
      matter interactions at the nanoscale and coupling of optical modes to electronic
      resonances. Furthermore, confinement of light can be taken to new extremes via
      coupling to the surface plasmon modes of metal nanostructures integrated with
      nanowires, leading to interesting physical phenomena. This Perspective will
      examine how the optical properties of semiconductor nanowires can be altered via
      their integration with highly confined plasmonic nanocavities that have resulted
      in properties such as orders of magnitude faster and more efficient light
      emission and lasing. The use of plasmonic nanocavities for tailored optical
      absorption will also be discussed in order to understand and engineer fundamental
      optical properties of these hybrid systems along with their potential for novel
      applications, which may not be possible with purely dielectric cavities.

PMID- 25396031
TI  - Successful use of antihistamines in severe hypereosinophilia.
AB  - Eosinophilia is common in childhood, and in most cases it is mild and of limited
      clinical relevance, being often secondary to allergy or infections. In rare
      cases, eosinophilia may be idiopathic or related to neoplastic aetiology. When
      severe and protracted, it can cause potentially irreversible organ or system
      damage, whose prevention is the first priority in the clinical management of
      hypereosinophilia. We describe the case of a patient with very severe
      eosinophilia, in whom antihistamines proved to be effective and safe in
      contributing to the eosinophil count normalization, thus avoiding the use of
      steroids until the hypothesis of an underlying neoplastic disorder was reasonably
      excluded. 

PMID- 25396032
TI  - Treatment of foodborne botulism in current clinical toxicology: authors' reply.

PMID- 25396033
TI  - Extravasation of antineoplastic agents: prevention and treatments.
AB  - The extravasation of antineoplastic agents is an unwanted and distressing
      situation that can easily occur. It may cause severe and irreversible local
      injuries. Left untreated, vesicant chemotherapy extravasation can potentially
      cause tissue necrosis, functional impairment and permanent disfigurement. This
      article provides a review of current literature regarding recommendations on the
      prevention and treatment of extravasation of antineoplastic agents. 

PMID- 25396034
TI  - Intrauterine growth standards: a cross-sectional study in a population of
      nigerian newborns.
AB  - The aim of the study was to define an intrauterine growth curve for a population
      of Nigerian newborn babies. A cross-sectional observational study design was
      adopted. Weight, length and head circumference were all measured in consecutive
      singleton deliveries at the University of Ilorin Teaching Hospital over a 3-year
      period. Gestational age (GA) of the babies was estimated from the last menstrual
      period or first trimester ultrasound. The estimates obtained were clinically
      validated using the Ballard score. Mean birth weights and percentiles of the
      weight, length and head circumferences for the respective GA were estimated using
      the SPSS 15 software package. A total of 5273 babies were recruited for the study
      with GA ranging from 25-44 weeks. Comparison of the mean birth weights of the
      various GA with the data from Denver, Colorado, showed that Nigerian babes tended
      to weigh less at the early GA, although these differences were not statistically
      significant. Between 26-36 weeks, the average weights of both sexes were similar;
      however, beyond this time point there was a consistent increase in the average
      weight of the males over the female babies. Growth curves for Nigerian newborn
      babies were generated and showed that the mean birth weight of Nigerian preterm
      babies was lighter than that of babies in Colorado. The impact of these
      differences on the classification of newborns will require further evaluation. 

PMID- 25396035
TI  - A case of shwachman-diamond syndrome distinguished from celiac disease.
AB  - Shwachman-Diamond syndrome (SDS) is a rare, inherited, autosomal recessive
      disease characterized by exocrine pancreatic dysfunction, skeletal problems and
      varying degrees of cytopenias resulting in bone marrow dysfunction. We report the
      first case of SDS that was difficult to distinguish from celiac disease because
      this is a valuable example of the variety in SDS presentation. 

PMID- 25396036
TI  - The godoy & godoy cervical stimulation technique in the treatment of primary
      congenital lymphedema.
AB  - THE AIM OF THE CURRENT STUDY IS TO REPORT ON THE TREATMENT OF PRIMARY LYMPHEDEMA
      USING A NEW FORM OF THERAPY: cervical stimulation. In a prospective cohort study,
      9 boys and 5 girls with primary congenital lymphedema were evaluated over two
      years. Age ranged from two months to 8.5 years. After diagnosis, all mothers were
      trained in the new technique. The Godoy & Godoy cervical stimulation technique
      consists of between 20 to 30 stimuli per minute using light movements in the
      cervical region. All the children were submitted to perimetric evaluations of the
      feet and legs; however, in this study only two points, 3 and 6 cm from the base
      of the big toe nail, were used. The two-tailed t-test was used for statistical
      analysis with an alpha error of 5% (P<0.05) considered acceptable. The size of
      the lymphedematous feet was reduced and even normalized (P<0.0001) for all
      treated children. Cervical stimulation is a new option in the treatment of
      primary congenital lymphedema; its association with compression stockings has a
      synergistic effect in reducing the volume of lymphedema. 

PMID- 25396037
TI  - Optimal position of a long-term central venous catheter tip in a pediatric
      patient with congenital diseases.
AB  - Progress in medical and scientific research has increased the chances of survival
      for young patients with congenital diseases, children who, in the past, would not
      have had any chance of survival. Nowadays, congenital diseases can be treated
      with appropriate replacement therapies. These treatments can be difficult to
      administer in young patients because of the high frequency of administration
      (sometimes more than a dose per week), the use of intravenous infusion and the
      long-term or life-term requirement. 

PMID- 25396038
TI  - Carbohydrate antigen delivery by water soluble copolymers as potential anti
      cancer vaccines.
AB  - Tumor associated carbohydrate antigens (TACAs) are overexpressed on tumor cells,
      which renders them attractive targets for anti-cancer vaccines. To overcome the
      poor immunogenicity of TACAs, we designed a polymer platform for antigen
      presentation by co-delivering TACA and helper T (Th) cell epitope on the same
      chain. The block copolymer was synthesized by cyanoxyl-mediated free radical
      polymerization followed by conjugation with a TACA Tn antigen and a mouse Th-cell
      peptide epitope derived from polio virus (PV) to afford the vaccine construct.
      The glycopolymer vaccine elicited an anti-Tn immune response with significant
      titers of IgG antibodies, which recognized Tn-expressing tumor cells.

PMID- 25396039
TI  - Flow cytometric characterization of brain dendritic cell subsets after murine
      stroke.
AB  - BACKGROUND: Sterile inflammation is a substantial element of post-stroke
      pathophysiology with the determination of autoimmunity versus tolerance being one
      of its most important aspects. It is believed that this determination is
      initiated relatively early after stroke onset by clearing macrophages and
      migratory dendritic cells (DC). However, the phenotypic differentiation of
      macrophages and DC is intricate particularly in the disease context. Here, we
      utilized a set of surface markers used in mucosal immunity research to
      investigate the involvement of macrophages and DC subpopulations in post-stroke
      inflammation in mice. FINDINGS: Photothrombotic stroke induced a significant
      increase of lineage (CD3, B220, Ly6G and CD49b) negative CD11b+ cells in the
      brain primarily consisting of F4/80+ macrophages and, to a lesser extent, F4/80
      /CD11c-/CD11b+ monocytes and F4/80-/CD11c+ DC. The latter could be differentiated
      into the classical migratory DC subpopulations (CD11b+ and CD103+), but no CD4 or
      CD8+ DC were found. Finally, stroke caused a significant increase of CD11b/CD103
      double-positive DC in the affected brain hemisphere. CONCLUSIONS: The surface
      marker combination used in this study allowed a phenotypic differentiation of
      macrophages and DC subpopulations after stroke, thus providing an important
      prerequisite to study post-stroke immunity and tolerance.

PMID- 25396040
TI  - Small Molecule Probes That Perturb A Protein-protein Interface In Antithrombin.
AB  - Small molecule probes for perturbing protein-protein interactions (PPIs) in vitro
      can be useful if they cause the target proteins to undergo biomedically relevant
      changes to their tertiary and quaternary structures. Application of the Exploring
      Key Orientations (EKO) strategy (J. Am. Chem. Soc., 2013, 135, 167 - 173) to a
      piperidinone-piperidine chemotype 1 indicated specific derivatives were
      candidates to perturb a protein-protein interface in the alpha-antithrombin
      dimer; those particular derivatives of 1 were prepared and tested. In the event,
      most of them significantly accelerated oligomerization of monomeric alpha
      antithrombin, which is metastable in its oligomeric state. This assertion is
      supported by data from gel electrophoresis (non-denaturing PAGE; throughout) and
      probe-induced loss of alpha-antithrombin's inhibitor activity in a reaction
      catalyzed by thrombin. Kinetics of alpha-antithrombin oligomerization induced by
      the target compounds were examined. It was found that probes with O-benzyl
      protected serine side-chains are the most active catalysts in the series, and
      reasons for this, based on modeling experiments, are proposed. Overall, this
      study reveals one of the first examples of small molecules designed to act at a
      protein-protein interface relevant to oligomerization of a serpin (ie alpha
      antithrombin). The relevance of this to formation of oligomeric serpin fibrils,
      associated with the disease states known as "serpinopathies", is discussed.

PMID- 25396041
TI  - Synthesis of diarylmethylamines via palladium-catalyzed regioselective arylation
      of 1,1,3-triaryl-2-azaallyl anions.
AB  - Diarylmethylamines are of great interest due to their prevalence in
      pharmaceutical chemistry. As a result, new methods for their synthesis are in
      demand. Herein, we report a versatile protocol for the synthesis of
      diarylmethylamine derivatives involving palladium-catalyzed arylation of in situ
      generated 2-azaallyl anion intermediates. The 2-azaallyl anions are generated by
      reversible deprotonation of readily available aldimine and ketimine precursors.
      Importantly, the arylated aldimine and ketimine products do not undergo
      isomerization under the reaction conditions. Scale-up of the arylation and
      hydrolysis of the resulting products to furnish diarylmethylamines were also
      successfully performed.

PMID- 25396042
TI  - The fusion of tissue spheroids attached to pre-stretched electrospun polyurethane
      scaffolds.
AB  - Effective cell invasion into thick electrospun biomimetic scaffolds is an
      unsolved problem. One possible strategy to biofabricate tissue constructs of
      desirable thickness and material properties without the need for cell invasion is
      to use thin (<2 um) porous electrospun meshes and self-assembling (capable of
      tissue fusion) tissue spheroids as building blocks. Pre-stretched electrospun
      meshes remained taut in cell culture and were able to support tissue spheroids
      with minimal deformation. We hypothesize that elastic electrospun scaffolds could
      be used as temporal support templates for rapid self-assembly of cell spheroids
      into higher order tissue structures, such as engineered vascular tissue. The aim
      of this study was to investigate how the attachment of tissue spheroids to pre
      stretched polyurethane scaffolds may interfere with the tissue fusion process.
      Tissue spheroids attached, spread, and fused after being placed on pre-stretched
      polyurethane electrospun matrices and formed tissue constructs. Efforts to
      eliminate hole defects with fibrogenic tissue growth factor-beta resulted in the
      increased synthesis of collagen and periostin and a dramatic reduction in hole
      size and number. In control experiments, tissue spheroids fuse on a non-adhesive
      hydrogel and form continuous tissue constructs without holes. Our data
      demonstrate that tissue spheroids attached to thin stretched elastic electrospun
      scaffolds have an interrupted tissue fusion process. The resulting tissue
      engineered construct phenotype is a direct outcome of the delicate balance of the
      competing physical forces operating during the tissue fusion process at the
      interface of the pre-stretched elastic scaffold and the attached tissue
      spheroids. We have shown that with appropriate treatments, this process can be
      modulated, and thus, a thin pre-stretched elastic polyurethane electrospun
      scaffold could serve as a supporting template for rapid biofabrication of thick
      tissue-engineered constructs without the need for cell invasion. 

PMID- 25396043
TI  - In vitro evaluation of bi-layer silk fibroin scaffolds for gastrointestinal
      tissue engineering.
AB  - Silk fibroin scaffolds were investigated for their ability to support attachment,
      proliferation, and differentiation of human gastrointestinal epithelial and
      smooth muscle cell lines in order to ascertain their potential for tissue
      engineering. A bi-layer silk fibroin matrix composed of a porous silk fibroin
      foam annealed to a homogeneous silk fibroin film was evaluated in parallel with
      small intestinal submucosa scaffolds. AlamarBlue analysis revealed that silk
      fibroin scaffolds supported significantly higher levels of small intestinal
      smooth muscle cell, colon smooth muscle cell, and esophageal smooth muscle cell
      attachment in comparison to small intestinal submucosa. Following 7 days of
      culture, relative numbers of each smooth muscle cell population maintained on
      both scaffold groups were significantly elevated over respective 1-day levels
      indicative of cell proliferation. Real-time reverse transcription polymerase
      chain reaction and immunohistochemical analyses demonstrated that both silk
      fibroin and small intestinal submucosa scaffolds were permissive for contractile
      differentiation of small intestinal smooth muscle cell, colon smooth muscle cell,
      esophageal smooth muscle cell as determined by significant upregulation of alpha
      smooth muscle actin and SM22alpha messenger RNA and protein expression levels
      following transforming growth factor-beta1 stimulation. AlamarBlue analysis
      demonstrated that both matrix groups supported similar degrees of attachment and
      proliferation of gastrointestinal epithelial cell lines including colonic T84
      cells and esophageal epithelial cells. Following 14 days of culture on both
      matrices, spontaneous differentiation of T84 cells toward an enterocyte lineage
      was confirmed by expression of brush border enzymes, lactase, and maltase, as
      determined by real-time reverse transcription polymerase chain reaction and
      immunohistochemical analyses. In contrast to small intestinal submucosa
      scaffolds, silk fibroin scaffolds supported spontaneous differentiation of
      esophageal epithelial cells toward a suprabasal cell lineage as indicated by
      significant upregulation of cytokeratin 4 and cytokeratin 13 messenger RNA
      transcript levels. In addition, esophageal epithelial cells maintained on silk
      fibroin scaffolds also produced significantly higher involucrin messenger RNA
      transcript levels in comparison to small intestinal submucosa counterparts,
      indicating an increased propensity for superficial, squamous cell specification.
      Collectively, these data provide evidence for the potential of silk fibroin
      scaffolds for gastrointestinal tissue engineering applications. 

PMID- 25396044
TI  - The Israeli National Committee for sex selection by pre-implantation genetic
      diagnosis: a novel approach (2005-2011).
AB  - BACKGROUND: Pre-implantation genetic diagnosis (PGD) for fetal sex selection
      raises complex dilemmas. In Israel, PGD is regulated by the Ministry of Health.
      It is basically prohibited, but exceptions can be made upon approval by the
      National Committee for Sex Selection by PGD for Non-Medical Reasons (the
      "Committee"). This report describes the Committee's work since its inception in
      May, 2005 through December, 2011. METHODS: Files were abstracted onto a
      structured form. Discrete variables were analyzed by chi-square analysis, and
      continuous variables by T-Test. RESULTS: During the study period 411 applications
      were received. Two-thirds of the applicants (n = 276; 67.2%) were Jewish and
      26.8% were Moslem Arab. Over two-thirds (n = 285; 69.3%) had no children of the
      requested sex and >=4 children of the opposite sex. Three-quarters of the
      requests were for a male (n = 308; 74.9%): 100% of Arab and 63% of Jewish
      applicants. Many noted more than one reason for their request. The most frequent
      category (n = 201; 48.9%) was a strong emotional desire, followed by medically
      related reasons (n = 83; 20.2%). For 216 applications a decision was arrived at,
      with 46 (21.3%) approved. Of the remaining 195 for 192 over a year had passed
      since last contact with the Committee. The likelihood of approval was higher if
      applicants met the criterion of >=4 same-sex children than if they didn't (33.7%
      vs. 11.6%, P = 0.001). The largest number of approvals were those requested for
      'emotional' reasons, while the highest approval rate was for religious reasons.
      CONCLUSIONS: This study reviewed the first seven years of Committee activity.
      Most requested males, and the primary reason was the parents' intense emotional
      desire. Only one-fifth of the decisions were approvals, possibly reflecting
      reluctance to encourage non-medically-indicated PGD, a viewpoint not unique to
      Israel. Limitations include the relatively small number of cases and lack of
      access to Committee deliberation protocols. It is recommended that longitudinal
      studies be conducted to gain insight into the consequences to individuals,
      couples and families--both those whose requests were approved and those denied--
      of this major step in reproductive technologies and in society's effort to
      respond to them.

PMID- 25352982
TI  - Monitoring drug promiscuity over time.
AB  - Drug promiscuity and polypharmacology are much discussed topics in pharmaceutical
      research. Experimentally, promiscuity can be studied by profiling of compounds on
      arrays of targets. Computationally, promiscuity rates can be estimated by mining
      of compound activity data. In this study, we have assessed drug promiscuity over
      time by systematically collecting activity records for approved drugs. For 518
      diverse drugs, promiscuity rates were determined over different time intervals.
      Significant differences between the number of reported drug targets and the
      promiscuity rates derived from activity records were frequently observed. On the
      basis of high-confidence activity data, an increase in average promiscuity rates
      from 1.5 to 3.2 targets per drug was detected between 2000 and 2014. These
      promiscuity rates are lower than often assumed. When the stringency of data
      selection criteria was reduced in subsequent steps, non-realistic increases in
      promiscuity rates from ~6 targets per drug in 2000 to more than 28 targets were
      obtained. Hence, estimates of drug promiscuity significantly differ depending on
      the stringency with which target annotations and activity data are considered. 

PMID- 25383188
TI  - Plasmodium falciparum infection rates for some Anopheles spp. from Guinea-Bissau,
      West Africa.
AB  - Presence of Plasmodium falciparum circumsporozoite protein (CSP) was detected by
      enzyme linked immunosorbent assay (ELISA) in a sample of Anopheles gambiae s.s.,
      A. melas and A. pharoensis collected in Guinea-Bissau during October and November
      2009. The percentage of P. falciparum infected samples (10.2% overall; confidence
      interval (CI): 7.45-13.6%) was comparable to earlier studies from other sites in
      Guinea-Bissau (9.6-12.4%). The majority of the specimens collected were
      identified as A. gambiae which had an individual infection rate of 12.6 % (CI:
      8.88-17.6) across collection sites. A small number of specimens of A. coluzzii,
      A. coluzzii x A. gambiae hybrids, A. melas and A. pharoensis were collected and
      had infection rates of 4.3% (CI:0.98-12.4), 4.1% (CI:0.35-14.5), 11.1% (CI:1.86
      34.1) and 33.3% (CI:9.25-70.4) respectively. Despite being present in low numbers
      in indoor collections, the exophilic feeding behaviors of A. melas (N=18) and A.
      pharoensis (N=6) and high infection rates observed in this survey suggest
      falciparum-malaria transmission potential outside of the protection of bed nets. 

PMID- 25396047
TI  - DNA sequencing by synthesis using 3'-O-azidomethyl nucleotide reversible
      terminators and surface-enhanced Raman spectroscopic detection.
AB  - As an alternative to fluorescence-based DNA sequencing by synthesis (SBS), we
      report here an approach using an azido moiety (N3) that has an intense, narrow
      and unique Raman shift at 2125 cm-1, where virtually all biological molecules are
      transparent, as a label for SBS. We first demonstrated that the four 3'-O
      azidomethyl nucleotide reversible terminators (3'-O-azidomethyl-dNTPs) displayed
      surface enhanced Raman scattering (SERS) at 2125 cm-1. Using these 4 nucleotide
      analogues as substrates, we then performed a complete 4-step SBS reaction. We
      used SERS to monitor the appearance of the azide-specific Raman peak at 2125 cm-1
      as a result of polymerase extension by a single 3'-O-azidomethyl-dNTP into the
      growing DNA strand and disappearance of this Raman peak with cleavage of the
      azido label to permit the next nucleotide incorporation, thereby continuously
      determining the DNA sequence. Due to the small size of the azido label, the 3'-O
      azidomethyl-dNTPs are efficient substrates for the DNA polymerase. In the SBS
      cycles, the natural nucleotides are restored after each incorporation and
      cleavage, producing a growing DNA strand that bears no modifications and will not
      impede further polymerase reactions. Thus, with further improvements in SERS for
      the azido moiety, this approach has the potential to provide an attractive
      alternative to fluorescence-based SBS.

PMID- 25396048
TI  - Benthic infaunal community structuring in an acidified tropical estuarine system.
AB  - BACKGROUND: Recent studies suggest that increasing ocean acidification (OA)
      should have strong direct and indirect influences on marine invertebrates. While
      most theory and application for OA is based on relatively physically-stable
      oceanic ecological systems, less is known about the effects of acidification on
      nearshore and estuarine systems. Here, we investigated the structuring of a
      benthic infaunal community in a tropical estuarine system, along a steep salinity
      and pH gradient, arising largely from acid-sulphate groundwater inflows (Sungai
      Brunei Estuary, Borneo, July 2011- June 2012). RESULTS: Preliminary data indicate
      that sediment pore-water salinity (range: 8.07 - 29.6 psu) declined towards the
      mainland in correspondence with the above-sediment estuarine water salinity
      (range: 3.58 - 31.2 psu), whereas the pore-water pH (range: 6.47- 7.72) was
      generally lower and less variable than the estuarine water pH (range: 5.78- 8.3),
      along the estuary. Of the thirty six species (taxa) recorded, the polychaetes
      Neanthes sp., Onuphis conchylega, Nereididae sp. and the amphipod Corophiidae
      sp., were numerically dominant. Calcified microcrustaceans (e.g., Cyclopoida sp.
      and Corophiidae sp.) were abundant at all stations and there was no clear
      distinction in distribution pattern along the estuarine between calcified and non
      calcified groups. Species richness increased seawards, though abundance (density)
      showed no distinct directional trend. Diversity indices were generally positively
      correlated (Spearman's rank correlation) with salinity and pH (p <0.05) and
      negatively with clay and organic matter, except for evenness values (p >0.05).
      Three faunistic assemblages were distinguished: (1) nereid-cyclopoid-sabellid,
      (2) corophiid-capitellid and (3) onuphid- nereid-capitellid. These respectively
      associated with lower salinity/pH and a muddy bottom, low salinity/pH and a sandy
      bottom, and high salinity/pH and a sandy bottom. However, CCA suggested that
      species distribution and community structuring is more strongly influenced by
      sediment particle characteristics than by the chemical properties of the water
      (pH and salinity). CONCLUSIONS: Infaunal estuarine communities, which are
      typically adapted to survive relatively acidic conditions, may be less exposed,
      less sensitive, and less vulnerable than epibenthic or pelagic communities to
      further acidification of above-sediment waters. These data question the extent to
      which all marine infaunal communities, including oceanic communities, are likely
      to be affected by future global CO2-driven acidification.

PMID- 25396049
TI  - Generation of rodent and human osteoblasts.
AB  - This paper describes the isolation, culture and staining of primary osteoblasts
      from neonatal rodents and human samples. The calvaria and long-bone assays allow
      direct measurement of bone matrix deposition and mineralisation, as well as
      producing osteoblasts at defined stages of differentiation for molecular and
      histological analysis. Culture of human osteoblasts enables cell function to be
      investigated in targeted patient groups. The described methods will provide a
      step-by-step guide of what to expect at each stage of the culture and highlight
      the varied tissue culture conditions required to successfully grow osteoblasts
      from different sources. A special focus of this paper is the methods used for
      analysis of bone mineralisation and how to ensure that nonspecific mineral
      deposition or staining is not quantified. 

PMID- 25396050
TI  - What bridges mineral platelets of bone?

PMID- 25396051
TI  - Computed tomography-based rigidity analysis: a review of the approach in
      preclinical and clinical studies.
AB  - The assessment of fracture risk in patients afflicted with osseous neoplasms has
      long presented a problem for orthopedic oncologists. These patients are at risk
      for developing pathologic fractures through lytic defects in the appendicular and
      axial skeleton with devastating consequences on their quality of life. Lesions
      with a high risk of fracture may require prophylactic surgical stabilization,
      whereas low-risk lesions can be treated conservatively. Therefore, effective
      prevention of pathologic fractures depends on accurate assessment of fracture
      risk and is a critical step to avoid debilitating complications. Given the
      complex nature of osseous neoplasms, treatment requires a multidisciplinary
      approach; yet, little consensus regarding fracture risk assessment exists among
      physicians involved in the care of these patients. In order to improve the
      overall standard of care, specific criteria must be adopted to formulate
      consistent and accurate fracture risk predictions. However, clinicians make
      subjective assessments about fracture risk on plain radiographs using guidelines
      now recognized to be inaccurate. Osseous neoplasms alter both the material and
      geometric properties of bone; failure to account for changes in both of these
      parameters limits the accuracy of current fracture risk assessments. Rigidity,
      the capacity to resist deformation upon loading, is a structural property that
      integrates both the material and geometric properties of bone. Therefore,
      rigidity can be used as a mechanical assay of the changes induced by lytic
      lesions to the structural competency of bone. Using this principle, computed
      tomography (CT)-based structural rigidity analysis (CTRA) was developed and
      validated in a series of preclinical and clinical studies. 

PMID- 25396052
TI  - The hunger games of skeletal metabolism.
AB  - Gastrointestinal peptides and adipokines are critical signalling molecules
      involved in controlling whole-body energy homeostasis. These circulating hormones
      regulate a variety of biological responses such as hunger, satiety and glucose
      uptake. In vivo experiments have established that these hormones also regulate
      bone metabolism, while associations between these hormones and bone mass have
      been observed in human clinical studies. With a focus on recent research, this
      review aims to describe the roles that gastrointestinal peptides (ghrelin,
      peptide YY, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1
      and glucagon-like peptide 2) and adipokines (leptin and adiponectin) have in bone
      metabolism and to examine their effects on bone in situations of altered
      metabolism, such as obesity. As the prevalence of obesity continues to increase,
      there is a growing interest in understanding the interactions between nutritional
      regulators from the gut and adipose tissue and their influence on bone mass. 

PMID- 25396053
TI  - Electrocardiogram-based scoring system for predicting secondary pulmonary
      hypertension: A cross-sectional study.
AB  - OBJECTIVES: In this study, we have developed an electrocardiogram-based scoring
      system to predict secondary pulmonary hypertension. DESIGN: A cross-sectional
      study. SETTING: Single tertiary-care hospital in Scranton, Pennsylvania, USA.
      PARTICIPANTS: Five hundred and fifty-two consecutive patients undergoing right
      heart catheterization between 2006 and 2009. MAIN OUTCOME MEASURES: Surface
      electrocardiogram was assessed for R-wave in lead V1 >= 6mm, R-wave in V6 <= 3mm,
      S-wave in V6 >= 3mm, right atrial enlargement, right axis deviation and left
      atrial enlargement. Pulmonary hypertension was defined as mean pulmonary artery
      pressure >=25 mmHg, determined by right heart catheterization. RESULTS: A total
      of 297 (54%) patients in the study cohort had pulmonary hypertension. In total,
      332 patients from the study cohort formed the development cohort and the
      remaining 220 patients formed the validation cohort. In the development cohort,
      based on log odds ratios of association, RAE, LAE, RAD, R-wave in V1 >= 6 mm were
      assigned scores of 5, 2, 2 and 1, respectively, to form a 10-point scoring system
      "Scranton PHT (SP) score". SP scores of 5 points and 7 points in DC showed C
      statistic of 0.83 and 0.89, respectively, for discriminating pulmonary
      hypertension. C-statistic for RAE alone was significantly lower compared to an SP
      score of 7 (0.83 vs. 0.89, P = 0.021). The reliability of SP score in the
      validation cohort was acceptable. CONCLUSION: SP score provides a good point-of
      care tool to predict pulmonary hypertension in patients with clinical suspicion
      of it.

PMID- 25396054
TI  - Health-related quality of life and long-term morbidity and mortality in patients
      hospitalised with systolic heart failure.
AB  - BACKGROUND: Health-related quality of life has been shown to impact prognosis in
      chronic heart failure, however with limited long-term follow-up. We analysed data
      spanning 8-12 years to assess the impact of health-related quality of life using
      the Nottingham Health Profile on first hospitalisation and mortality, for
      cardiovascular and all causes. METHODS: We included 208 patients aged >=60 years
      with New York Heart Association class II-IV and left ventricular systolic
      dysfunction hospitalised in Stockholm during 1996-99. Data on hospital
      admissions, discharge diagnoses and date and cause of death were collected from
      administrative databases and medical records until 2007. Cox proportional hazard
      models were employed to analyse the time to event for mortality and
      hospitalisations. RESULTS: Mean age was 76 years, 58% were male and mean ejection
      fraction was 34%. Median survival was 4.6 years (range 6 days-11.9 years); 148
      patients died. All-cause and cardiovascular mortality were determined by physical
      mobility (by Nottingham Health Profile), age, gender, diuretic dose and
      haemoglobin level. Glomerular filtration rate was significant for all-cause
      mortality, while atrioventricular plane displacement was predictive of
      cardiovascular mortality. Median time to first all-cause and cardiovascular
      hospitalisation was 5.7 and 11.2 months, respectively. Time to first all-cause
      hospitalisation was determined by physical mobility, emotional reactions, age,
      gender and haemoglobin level, while only physical mobility and diuretic dose
      predicted time to first cardiovascular hospitalisation. CONCLUSIONS: In
      conclusion, in patients with systolic chronic heart failure, physical mobility as
      part of health-related quality of life is an independent prognostic marker for
      cardiovascular and all-cause readmissions and mortality over 12 years.

PMID- 25396055
TI  - Cardiac rehabilitation with a nurse case manager (GoHeart) across local and
      regional health authorities improves risk factors, self-care and psychosocial
      outcomes. A one-year follow-up study.
AB  - OBJECTIVES: In Denmark, the local and regional health authorities share
      responsibility for cardiac rehabilitation (CR). The objective was to assess
      effectiveness of CR across sectors coordinated by a nurse case manager (NCM).
      DESIGN: A one-year follow-up study. SETTING: A CR programme (GoHeart) was
      evaluated in a cohort at Lillebaelt Hospital Vejle, DK from 2010 to 2011.
      PARTICIPANTS: Consecutive patients admitted to CR were included. The inclusion
      criteria were the event of acute myocardial infarction or stable angina and
      invasive revascularization (left ventricular ejection fraction (LVEF) >=45%).
      MAIN OUTCOME MEASURES: Cardiac risk factors, stratified self-care and self
      reported psychosocial factors (SF12 and Hospital Anxiety and Depression Scale
      (HADS)) were assessed at admission (phase IIa), at three months at discharge
      (phase IIb) and at one-year follow-up (phase III). Intention-to-treat and
      predefined subgroup analysis on sex was performed. RESULTS: Of 241 patients, 183
      (75.9%) were included (mean age 63.8 years). At discharge improvements were found
      in total-cholesterol (p < 0.001), low density lipoprotein (LDL; p < 0.001),
      functional capacities (metabolic equivalent of tasks (METS), p < 0.01), self-care
      management (p < 0.001), Health status Short Form 12 version (SF12; physical; p <
      0.001 and mental; p < 0.01) and in depression symptoms (p < 0.01). At one-year
      follow-up these outcomes were maintained; additionally there was improvement in
      body mass index (BMI; p < 0.05), and high density lipoprotein (HDL; p < 0.05).
      There were no sex differences. CONCLUSION: CR shared between local and regional
      health authorities led by a NCM (GoHeart) improves risk factors, self-care and
      psychosocial factors. Further improvements in most variables were at one-year
      follow-up.

PMID- 25396056
TI  - Value of repeat biopsy in lupus nephritis flares.
AB  - OBJECTIVES: Renal flares are common in lupus nephritis (LN), and class switch is
      thought to be characteristic. There is no agreement on indications for performing
      a repeat renal biopsy. Our objective was to retrospectively review patients who
      had more than one renal biopsy performed on clinical indications, and analyse
      clinical, pathological and treatment changes after successive biopsies. METHODS:
      Forty-five patients with LN and one or more repeat renal biopsies were included,
      with a total of 116 biopsies. RESULTS: Of the 71 repeat biopsies, pathological
      transition occurred in 39 (54.9%). When having a previous biopsy with a
      proliferative lesion, class switch occurred in 55.6%, with 24.4% evolving into
      non-proliferative classes. When previous biopsy was class V, transition to other
      classes occurred in 58.3% and changes were all into proliferative classes.
      Conversion from one pure proliferative form to another (class III to class IV or
      vice versa) happened in 11.3% of the rebiopsies, with 62 rebiopsies (87.3%)
      leading to a change in the treatment regimen. CONCLUSIONS: Histological
      transformations were common, and they occurred when the previous biopsy had non
      proliferative lesions as well as when lesions were proliferative. Treatments were
      modified after repeat renal biopsy in the majority of patients. In this
      experience, kidney repeat biopsies were useful in guiding treatment of LN flares.

PMID- 25396057
TI  - Which outcome measures in SLE clinical trials best reflect medical judgment?
AB  - OBJECTIVES: TO COMPARE TWO MEASURES OF SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
      RESPONSE: the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus
      Assessment (BICLA) and the Systemic Lupus Responder Index (SRI) against a
      clinician's assessment of improvement. METHODS: Ninety-one lupus patients were
      identified with two visits at which Systemic Lupus Erythematosus Disease Activity
      Index (SLEDAI) and BILAG had been scored and with active disease (SLEDAI>=6) at
      the first visit. A physician rated the disease activity at the second visit as
      clinically significant improvement, no change or worsening. SRI and BICLA were
      scored both with and without the medication criteria often used in trials to
      restrict response definitions. RESULTS: 68 patients were considered improved, 17
      same and 6 worse at follow-up. SRI versus BICLA, performed without considering
      medication changes, captured physician-rated improvement with 85% vs 76%
      sensitivity and 74% vs 78% specificity. With medication limits both instruments
      had 37% sensitivity and 96% specificity for physician-assessed improvement. Seven
      patients considered improved by the clinician met the BICLA but not the SRI
      definition of improvement by failing to achieve a four-point improvement in
      SLEDAI. 13 clinician-rated responders met SRI but not BICLA by improving in less
      than all organs. CONCLUSIONS: Shortfalls of SRI and BICLA may be due to BICLA
      only requiring partial improvement but in all organs versus SRI requiring full
      improvement in some manifestation(s) and not all organs. SRI and BICLA with
      medication restrictions are less likely to denote response when the physician
      disagrees and could provide stringent proof of efficacy in appropriately powered
      clinical trials.

PMID- 25396058
TI  - Clinical phenotype associations with various types of anti-dsDNA antibodies in
      patients with recent onset of rheumatic symptoms. Results from a multicentre
      observational study.
AB  - Despite anti-dsDNA antibodies constitute a wide range of specificities, they are
      considered as the hallmark for systemic lupus erythematosus (SLE). OBJECTIVE: To
      identify clinical phenotypes associated with anti-dsDNA antibodies, independently
      of any clinical diagnoses. METHODS: Patients with recent onset of any rheumatic
      symptoms were screened for antinuclear antibodies (ANA). All ANA-positive and
      matching ANA-negative patients were examined, and their clinical phenotypes were
      registered, using a systematic chart formulated after consensus between the
      participating centres. All patients were tested for different anti-dsDNA antibody
      specificities with assays habitually used in each participating laboratory.
      Crithidia Luciliae Immuno Fluorescence Test (CLIFT) was performed three times
      (with two different commercial kits); solid and solution phase ELISA were
      performed four times. Associations between clinical phenotypes and results of
      anti-dsDNA assays were evaluated by linear regression analysis (LRA) and
      principal component analysis (PCA). RESULTS: Totally, 292 ANA-positive and 292
      matching ANA-negative patients were included in the study. A full dataset for
      statistical analysis was obtained in 547 patients. Anti-dsDNA antibodies were
      most frequently detected by ELISA. LRA showed that overall positivity of anti
      dsDNA antibodies was associated with proteinuria and pleuritis. Alopecia was
      significantly associated only with CLIFT-positivity. Besides confirming the same
      findings, PCA showed that combined positivity of CLIFT and ELISA was also
      associated with lymphopenia. CONCLUSIONS: Our results show that different anti
      dsDNA antibody specificities are associated with nephropathy, pleuritis, alopecia
      and lymphopenia, regardless of the diagnosis. It may challenge the importance of
      anti-dsDNA antibodies as a diagnostic hallmark for SLE.

PMID- 25396059
TI  - Necrotising fasciitis in systemic lupus erythematosus: a case report and
      literature review.
AB  - Necrotising fasciitis (NF) is a rare infection of the subcutaneous tissue, known
      to be rapidly progressive and potentially fatal. Patients with systemic lupus
      erythematosus (SLE) may be predisposed to this condition, and early clinical
      recognition can be difficult. We report a case of necrotising fasciitis in a 26
      year-old woman with SLE. She presented with painful swelling of her left leg,
      then developed clinical features of septic shock. Emergency debridement was
      performed. Intraoperative findings revealed NF and cultures grew Pseudomonas
      aeruginosa. The patient survived after a lengthy hospital admission, following
      several further debridements complicated by recurrent chest sepsis and multiorgan
      failure. We also review and discuss the published cases of NF in SLE patients. 

PMID- 25396061
TI  - Pathogenic autoantibodies from patients with lupus nephritis cause reduced
      tyrosine phosphorylation of podocyte proteins, including tubulin.
AB  - INTRODUCTION: The tertiary structure of normal podocytes prevents protein from
      leaking into urine. Patients with lupus nephritis (LN) develop proteinuria, and
      kidney biopsies from these patients display a number of podocyte abnormalities
      including retraction of podocyte processes. Autoantibodies have been shown to
      deposit in the kidneys of patients and mice with LN and are believed to play a
      key role in causing renal inflammation and dysfunction. The objective of this
      research was to study the effects of IgG antibodies from patients with LN on
      cultured human podocytes. METHODS: We exposed a human podocyte cell line to heat
      inactivated (HI) plasma and purified polyclonal IgG from the following groups of
      subjects; patients with LN, patients with lupus without nephritis, patients with
      rheumatoid arthritis and healthy controls. We measured expression and
      intracellular distribution of podocyte-specific proteins and global
      phosphorylation of tyrosine. We then used mass spectrometry to identify the major
      protein targets of this phosphorylation. RESULTS: HI LN plasma did not alter
      expression or cellular distribution of podocyte-specific proteins but caused a
      significant reduction in podocyte protein tyrosine phosphorylation compared with
      plasma from healthy controls (p=0.0008). This result was replicated using
      purified IgG but was not seen with plasma from rheumatoid arthritis or non-renal
      lupus patients. The dominant tyrosine phosphorylated protein in podocytes was 55
      kDa in size and was identified as tubulin. CONCLUSIONS: Since tubulin is an
      important component of podocyte major processes, these results suggest that
      autoantibodies from LN patients may exert an important pathogenic effect by
      dephosphorylation of this protein in podocytes.

PMID- 25396060
TI  - Vitamin D deficiency is common and associated with increased C-reactive protein
      in children and young adults with lupus: an Atherosclerosis Prevention in
      Pediatric Lupus Erythematosus substudy.
AB  - OBJECTIVE: Epidemiological associations suggest vitamin D may play a role in
      inflammation and atherosclerosis. Using frozen serum and data from the
      Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we
      assessed associations between 25-hydroxyvitamin D [25(OH)D] and measures of
      systemic lupus erythematosus (SLE) disease activity and cardiovascular risk.
      METHODS: Baseline APPLE serum samples were used to measure 25(OH)D levels.
      Logistic regression models for vitamin D deficiency [25(OH)D levels <20 ng/mL]
      were constructed using baseline variables collected as part of the trial,
      including race, season, latitude, disease duration, disease activity, high
      sensitivity C-reactive protein (hsCRP), proteinuria, fasting lipids and carotid
      intima medial thickness (CIMT). RESULTS: Samples were available from 201 of 221
      APPLE subjects; 61/201 (30%) had vitamin D deficiency at baseline. In univariable
      analysis, baseline vitamin D deficiency was associated with season (p<0.01),
      minority status (p<0.01), body mass index (p=0.04), duration of SLE (p<0.01),
      SLICC damage index (p=0.04), hsCRP (p<0.01), mean-max CIMT (p=0.01), LDL
      cholesterol (p=0.03) and timed urine protein (p=0.03). In multivariable
      modelling, vitamin D deficiency was associated with age, latitude, season,
      minority status, proteinuria and hsCRP. CONCLUSIONS: Vitamin D deficiency is
      common in paediatric lupus and is independently associated with elevated hsCRP, a
      marker of inflammation that predicts cardiovascular disease risk. Although
      association is not proof of causation, this association is novel in the
      paediatric SLE population and suggests that vitamin D deficiency may contribute
      to heightened inflammation and cardiovascular risk in this population. TRIAL
      REGISTER NUMBER: NCT00065806.

PMID- 25396062
TI  - Reduced response to Epstein-Barr virus antigens by T-cells in systemic lupus
      erythematosus patients.
AB  - OBJECTIVE: Epstein-Barr virus (EBV) has for long been associated with systemic
      lupus erythematosus (SLE). In this study, we investigated the levels of latent
      and lytic antigen EBV-specific T-cells and antibodies in SLE patients. METHODS: T
      cells were analyzed by flow cytometry and antibodies were analyzed by enzyme
      linked immunosorbent assay. RESULTS: SLE patients showed a significantly reduced
      number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear
      antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples
      compared with healthy controls. Also, a reduced number of T-cells from SLE
      patients were found to produce interferon-gamma upon stimulation with these
      antigens. Importantly, responses to a superantigen were normal in SLE patients.
      Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but
      higher titres of antibodies against EBV. Furthermore, an inverse correlation was
      revealed between the number of lytic antigen EBV-specific T-cells and disease
      activity of the SLE patients, with high-activity SLE patients having fewer T
      cells than low-activity SLE patients. CONCLUSIONS: These results indicate a
      limited or a defective EBV-specific T-cell response in SLE patients, which may
      suggest poor control of EBV infection in SLE with an immune reaction shift
      towards a humoral response in an attempt to control viral reactivation. A role
      for decreased control of EBV as a contributing agent in the development or
      exacerbation of SLE is proposed.

PMID- 25396063
TI  - Causes and outcome of hospitalisations in Tunisian patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To describe the most common reasons of admission of Tunisian patients
      with systemic lupus erythematosus (SLE) and the outcomes of these
      hospitalisations. METHOD: The charts of patients with SLE who were hospitalised
      at our Department of Internal Medicine during a 2-year period from January 2011
      to December 2012 were retrospectively reviewed, and the demographic
      characteristics, clinical and laboratory features, as well as all comorbidities,
      were collected. RESULTS: There were 128 episodes of hospitalisation of 87
      patients with SLE. 25 patients (28.7%) were admitted twice or more. The median
      length of stay for all admissions was 11 days (2-76). The total number of days of
      hospitalisation was 1896 days, which represent 10.7% of the total number of days
      of hospitalisation in our department. The most common overall reason for
      hospitalisation was active SLE (55 events, 43%). In 29 patients, SLE was newly
      diagnosed during hospitalisation. Other causes of hospitalisation included
      assessment of the disease, infections (9.4%) and associated autoimmune disease
      (6.25%). Adverse drug reaction (3.1%) and thromboembolic events (1.25%) were
      uncommon causes of hospitalisations. There was a significant difference in length
      of stay between patients admitted with SLE flare and those admitted for non-SLE
      flare reasons (p<0.01). Four hospitalisations (3%) resulted in death. The
      principal cause of death was active SLE. CONCLUSIONS: Hospitalisation of patients
      with SLE is common in our department. Our study of this North African SLE
      population confirms the findings of previous studies suggesting that active SLE
      and infection remain the most common causes of hospitalisation of patients with
      SLE.

PMID- 25396064
TI  - Editorial.

PMID- 25396065
TI  - Clinical, laboratory and health-related quality of life correlates of Systemic
      Lupus Erythematosus Responder Index response: a post hoc analysis of the phase 3
      belimumab trials.
AB  - OBJECTIVE: Correlates of systemic lupus erythematosus (SLE) Responder Index (SRI)
      response with clinical trial end points were examined using pooled data from the
      Study of Belimumab in Subjects with SLE (BLISS) trials (N=1684). METHODS: Changes
      in clinical, laboratory and health-related quality of life measures from baseline
      at 52 weeks were compared between SRI responders (n=761) and non-responders
      (n=923). RESULTS: More SRI responders than non-responders had >=4-point (100% vs
      3.8%) and >=7-point (40.3% vs 1.3%) Safety of Estrogens in Lupus Erythematosus
      National Assessment-Systemic Lupus Erythematosus Disease Activity Index
      reductions, no new British Isles Lupus Assessment Group (BILAG) A and <=1 new B
      scores (91.9% vs 35.9%), and a 25% reduction in corticosteroid dose decrease of
      25% from >7.5 mg/d to <=7.5 mg/d (25.5% vs 13.9%), and fewer had a corticosteroid
      increase from <=7.5 mg/d to >7.5 mg/d (4.1% vs 21.3%; all p<0.001). More
      responders than non-responders had improved organ domains: Safety of Estrogens in
      Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease
      Activity Index (mean 1.45 vs 0.40), BILAG (2.00 vs 0.39), and greater improvement
      in Physician's Global Assessment (all p<0.001). Risks for developing any SLE
      flare or severe flare were reduced in responders by 42% and 87%, respectively
      (p<0.001). Responders reported greater improvements in Medical Outcomes Survey
      Short Form version 2 Physical and Mental Components and all domain scores, and
      Functional Assessment of Chronic Illness Therapy-Fatigue score compared with non
      responders (all p<0.001). CONCLUSION: Overall, SRI response in patients with
      active, autoantibody-positive SLE was associated with improvements in clinical,
      laboratory and patient-reported outcome measures, indicating that SRI response
      was associated with a global benefit. TRIAL REGISTRATION NUMBER: NCT00424476;
      NCT00410384.

PMID- 25396066
TI  - sIL7R concentrations in the serum reflect disease activity in the lupus kidney.
AB  - OBJECTIVES: Evaluation of disease activity in systemic lupus erythematosus (SLE)
      nephritis is a challenge, and repeated renal biopsies are usually needed in order
      to confirm a suspicion of flare. In a previous cross-sectional study, we reported
      that serum soluble form of the interleukin-7 receptor (sIL7R) levels is strongly
      associated with nephritis in SLE patients. In the present study, we wanted to
      confirm the association between changes in serum sIL7R concentrations and renal
      disease activity in a large longitudinal cohort of SLE nephritis patients.
      METHODS: Sera were harvested longitudinally in 105 SLE nephritis patients. Serum
      sIL7R cut-off value for the detection of SLE nephritis activity was determined as
      the mean sIL7R concentration in non-nephritis SLE patients + 2 SDs using data
      collected in our previous study. Patients with glomerular filtration rate (GFR)
      <60 mL/min/1.73 m(2) (n=17) were excluded from the study due to persistently
      elevated serum sIL7R values. RESULTS: Serum sIL7R concentrations above the renal
      cut-off value were observed in 25 (out of 88) patients with a normal GFR. These
      patients had significantly higher serum double-stranded DNA (dsDNA) Ab and
      urinary protein to creatinine (UPC) ratio. Strikingly, 12 of them developed a
      renal British Isles Lupus Assessment Group index (BILAG) A within the next 3
      months, while this was only the case in four out of the 63 other patients
      (p<0.0001). The test had 75.0% sensitivity and 81.9% specificity for the
      detection of a renal BILAG A. Combination of serum sIL7R with any of the
      classical tests (anti-dsDNA Ab titres, UPC ratio, serum C3) resulted in an
      increased specificity for the detection of a renal flare. Administration of
      immunosuppressive therapy resulted in a significant decrease in serum sIL7R
      concentrations. CONCLUSIONS: Serum sIL7R is a sensitive and specific marker of
      renal disease activity in SLE. Elevated serum sIL7R values in SLE patients are
      associated with or predict the occurrence of an SLE nephritis flare.

PMID- 25396068
TI  - Blood-based candidate biomarkers of the presence of neuropsychiatric systemic
      lupus erythematosus in children.
AB  - OBJECTIVE: To examine select brain-reactive proteins for their usefulness to
      serve as blood-based biomarkers in the screening for neurocognitive deficits in
      childhood-onset systemic lupus erythematosus (cSLE-NCD). METHODS: Patients
      withcSLE (n=40) were studied longitudinally (month 1; month 18): working memory,
      psychomotor speed and visuoconstructional ability were assessed using formal
      neurocognitive testing to determine the presence of cSLE-NCD. Patients also
      completed the computerised Paediatric Automated Neuropsychological Assessment
      Metrics. The following brain-reactive proteins were measured in the blood:
      neutrophil gelatinase associated lipocalin (NGAL), S100B, S100A8/9, antibodies to
      NR2 glutamate receptor (aNR2-AB), ribosomal-P (aP-AB), glycoprotein-1 (aGP1-AB),
      and lupus anticoagulant. RESULTS: cSLE-NCD was present in 6 of 40 patients at
      baseline and 4 of 27 patients with 18-month information. aP-AB positivity was
      more commonly present with cSLE-NCD than without (p=0.05). aP-ABs were negatively
      associated with performance on tests assessing working memory, psychomotor speed
      and visuoconstructional ability in using formal neurocognitive testing. There
      were also significant negative associations between aP-AB, S100A8/9, aNR2-AB,
      aGP1-AB, and lupus anticoagulant and accuracy rates on select Paediatric
      Automated Neuropsychological Assessment Metrics subtests (p<0.05). Over time,
      decline in cognitive performance was more pronounced among patients with higher
      NGAL and aNR2-AB levels. Combinations of serum levels of S100A8/9, S100B, NGAL,
      aNR2-AB and aP-AB were able to identify cSLE-NCD (sensitivity: 100%; specificity
      76%) in exploratory analysis. CONCLUSIONS: Select brain-reactive proteins in the
      blood are associated with cognitive performance and the presence of cSLE-NCD,
      cross-sectionally and over time. This raises the possibility that testing of
      these proteins may assist with the screening of cSLE-NCD.

PMID- 25396067
TI  - Vitamin D status is a determinant of atorvastatin effect on carotid intima medial
      thickening progression rate in children with lupus: an Atherosclerosis Prevention
      in Pediatric Lupus Erythematosus (APPLE) substudy.
AB  - OBJECTIVE: Epidemiological associations suggest that vitamin D status may play a
      role in inflammation and progression of atherosclerosis. Using frozen serum,
      carotid intima medial thickness (CIMT) measurements and other existing data from
      the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we
      assessed interactions between serum 25-hydroxyvitamin D (25(OH)D), atorvastatin
      randomisation and CIMT progression rate. METHODS: Participants in the 3-year
      APPLE trial were randomised to placebo or atorvastatin and CIMT progression rate
      was measured. Baseline frozen serum was used to measure 25(OH)D concentrations.
      Mixed effect longitudinal models for CIMT progression at 3 years were used to
      evaluate interaction between vitamin D deficiency (serum 25(OH)D <20 ng/mL) at
      baseline and atorvastatin or placebo treatment, adjusting for key systemic lupus
      erythematosus disease variables and cardiovascular risk factors. RESULTS: 201/221
      APPLE participants had available samples and were included in this analysis;
      61/201 (30%) had vitamin D deficiency at baseline. In adjusted longitudinal
      modelling, there was significant interaction between baseline vitamin D
      deficiency and atorvastatin randomisation in 3-year progression of mean-max CIMT.
      In four out of six carotid segments, there was a greater decrease in mean-max
      CIMT progression rate in subjects who were treated with atorvastatin compared
      with placebo if they had baseline serum 25(OH)D levels >=20 ng/mL. CONCLUSIONS:
      Subjects with serum 25(OH)D >=20 ng/mL had less mean-max CIMT progression
      following 3 years of atorvastatin treatment. Results from secondary analyses must
      be interpreted cautiously, but findings suggest that underlying vitamin D
      deficiency may be involved in response to atorvastatin in atherosclerosis
      prevention. TRIAL REGISTRATION NUMBER: NCT00065806.

PMID- 25396069
TI  - Brain MRI in patients with diffuse psychiatric/neuropsychological syndromes in
      systemic lupus erythematosus.
AB  - BACKGROUND: Manifestations in neuropsychiatric systemic lupus erythematosus
      (NPSLE), especially active diffuse NPSLE syndromes, are some of the most
      difficult complications of the disease. For the evaluation and the diagnosis of
      central nervous system manifestations, including NPSLE, MRI is a very useful tool
      to detect the various abnormalities. However, the relationship between brain MRI
      findings and clinical variables has not yet been clarified in patients with
      diffuse NPSLE. OBJECTIVES: The aim of this study is to investigate the
      pathogenesis of diffuse NPSLE, by comparing various parameters such as serum
      autoantibodies and cytokines in cerebrospinal fluid (CSF) with abnormal findings
      revealed on brain MRIs in patients with diffuse NPSLE. METHODS: Fifty-three
      patients with diffuse NPSLE admitted to our University Hospital from 1992 to 2012
      were exhaustively enrolled in this study. Their medical charts and brain MRI
      scans were reviewed. The relationship of MRI abnormalities with various
      parameters was analysed. RESULTS: As many as 25 of 53 patients (47.2%) had
      abnormal MRI findings. MRI findings improved after treatment in 10 of 17 patients
      for whom follow-up studies were available. MRI abnormalities were not correlated
      with age at the onset of diffuse NPSLE. However, the disease duration of SLE was
      significantly longer in patients with abnormal MRI findings (p=0.0009). MRI
      abnormalities were not significantly associated with serum autoantibodies.
      However, there were significant elevations of the CSF protein level (p=0.0106)
      and the CSF interleukin 6 level (p=0.0225) in patients with abnormal MRI
      findings. Patients with MRI abnormalities showed significantly higher overall
      mortality (p=0.0348). CONCLUSIONS: The results revealed that MRI abnormalities in
      diffuse NPSLE might be heterogeneous with regard to their reversibility. These
      data also indicate that patients with diffuse NPSLE and MRI abnormalities have
      more severe inflammation in the central nervous system related to the activity of
      diffuse NPSLE, as evidenced by poorer prognosis.

PMID- 25396070
TI  - Cell-bound complement activation products in systemic lupus erythematosus:
      comparison with anti-double-stranded DNA and standard complement measurements.
AB  - OBJECTIVE: To compare the performance characteristics of cell-bound complement
      (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with
      antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in
      systemic lupus erythematosus (SLE). METHODS: The study enrolled 794 subjects
      consisting of 304 SLE and a control group consisting of 285 patients with other
      rheumatic diseases and 205 normal individuals. Anti-dsDNA and other
      autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d
      were determined using flow cytometry. Complement proteins were determined using
      immunoturbidimetry. Disease activity in SLE was determined using a non
      serological Systemic Lupus Erythematosus Disease Activity Index SELENA
      Modification. A two-tiered methodology combining CBCAPS with autoantibodies to
      cellular and citrullinated antigens was also developed. Statistical analyses used
      area under receiver operating characteristic curves and calculations of area
      under the curve (AUC), sensitivity and specificity. RESULTS: AUC for EC4d (0.82+/
      0.02) and BC4d (0.84+/-0.02) was higher than those yielded by C3 (0.73+/-0.02)
      and C4 (0.72+/-0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC
      yielded by anti-dsDNA (0.79+/-0.02), but significance was only achieved for BC4d
      (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology
      with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded
      80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to
      92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with
      SLE with higher levels of disease activity tested positive for elevated CBCAPS,
      reduced complement and anti-dsDNA (p<0.03). CONCLUSIONS: CBCAPS have higher
      sensitivity than standard complement and anti-dsDNA measurements, and may help
      with the differential diagnosis of SLE in combination with other autoantibodies.

PMID- 25396071
TI  - Change in the immunophenotype of a somatotroph adenoma resulting in gigantism.
AB  - BACKGROUND: Examining the pathologic progression of a pituitary adenoma from the
      point of a prepubescent child to an adult with gigantism affords us an
      opportunity to consider why patients may develop secretory or functioning tumors
      and raises questions about whether therapeutic interventions and surveillance
      strategies could be made to avoid irreversible phenotypic changes. CASE
      DESCRIPTION: A patient underwent a sublabial transsphenoidal resection for a
      clinically non-functioning macroadenoma in 1999. He underwent radiation treatment
      and was transiently given growth hormone (GH) supplementation as an adolescent.
      His growth rapidly traversed several percentiles and he was found to have
      elevated GH levels. The patient became symptomatic and was taken for a second
      neurosurgical procedure. Pathology and immunohistochemical staining demonstrated
      a significantly higher proportion of somatotroph cells and dense granularity; he
      was diagnosed with a functional somatotroph adenoma. CONCLUSIONS: While it is
      likely that the described observations reflect the manifestations of a functional
      somatotroph adenoma in development, it is possible that pubertal growth, GH
      supplementation, its removal, or radiation therapy contributed to the described
      endocrine and pathologic changes.

PMID- 25396072
TI  - Recanalization of a ruptured vertebral artery dissecting aneurysm after occlusion
      of the dilated segment only.
AB  - BACKGROUND: Internal trapping in which the dissecting aneurysm is occluded
      represents reliable treatment to prevent rebleeding of ruptured vertebral artery
      (VA) dissecting aneurysms. Various methods of internal trapping are available,
      but which is most appropriate for preventing both recanalization of the VA and
      procedural complications is unclear. CASE DESCRIPTION: A 61-year-old male
      presented with subarachnoid hemorrhage caused by rupture of a left VA dissecting
      aneurysm. Only the dilated segment of the aneurysm was occluded by coil
      embolization. Sixteen days after embolization, angiography showed recanalization
      of the treated left VA with blood supplying the dilated segment of the aneurysm,
      which showed morphological change between just proximal to the coil mesh and just
      distal to a coil, and antegrade blood flow through this part. Pathological
      examination showed that the rupture site that had appeared to be the most dilated
      area on angiography was located just above the orifice of the entrance. However,
      we think that this case of ruptured aneurysm had an entrance into a pseudolumen
      that existed proximal to the dilated segment, with antegrade recanalization
      occurring through the pseudolumen with morphological change because of
      insufficient coil obliteration of the entrance in the first therapy. CONCLUSIONS:
      This case suggests that occlusion of both the proximal and dilated segments of a
      VA dissecting aneurysm will prevent recanalization, by ensuring that any entrance
      to a pseudolumen of the aneurysm is completely closed. Careful follow-up after
      internal trapping is important, since antegrade recanalization via a pseudolumen
      may occur in the acute stage.

PMID- 25396073
TI  - Fibromyalgia and arachnoiditis presented as an acute spinal disorder.
AB  - BACKGROUND: Adhesive arachnoiditis is a chronic, insidious condition that causes
      debilitating intractable pain and a range of other neurological problems. Its
      pathophysiology is not well understood. This manuscript discusses its
      presentations, which can mimic an acute spinal disorder, its hypothetical
      pathophysiology, treatment, and its relationship with fibromyalgia. CASE
      DESCRIPTION: The authors present a case of a 47-year-old female who presented
      with clinical features mimicking an acute spinal disorder but later found to have
      an adhesive arachnoiditis. She was admitted following a trauma with complaints of
      back pain and paraplegia. On examination, there was marked tenderness over
      thoracolumbar spine with lower limbs upper motor neuron weakness. An urgent
      magnetic resonance imaging (MRI) of the spine revealed multiple lesions at her
      thoracic and lumbar spinal canals, which did not compress the spinal cord.
      Therefore, conservative management was initiated. Despite on regular therapies,
      her back and body pain worsened and little improvement in her limbs power was
      noted. Laminectomy was pursued and found to have spinal cord arachnoiditis.
      Subsequently, she was operated by other team members for multiple pelvic masses,
      which later proved to be benign. After gathering all the clinical information
      obtained at surgery and after taking detailed history inclusive of cognitive
      functions, diagnosis of an adhesive arachnoiditis syndrome was made. Currently,
      she is managed by neuropsychologist and pain specialist. CONCLUSION: This case
      report highlights the importance of knowing an adhesive arachnoiditis syndrome -
      a rarely discussed pathology by the neurosurgeon, which discloses a significant
      relationship between immune and nervous systems.

PMID- 25396074
TI  - Brucella-related multiple cerebral aneurysms: Report of a case and review of the
      literature.
AB  - BACKGROUND: Mycotic cerebral aneurysms are uncommon. We intend to report the
      first case of multiple mycotic cerebral aneurysms due to Brucella infection that
      were treated surgically. CASE DESCRIPTION: A 34-year-old man with
      neurobrucellosis presented with intracerebral haemorrhage (ICH). Three mycotic
      aneurysms were detected in the vicinity of middle cerebral artery (MCA). Medical
      treatment failed to treat them and aneurysms had to be managed surgically.
      CONCLUSION: Brucella-related cerebral mycotic aneurysm has rarely been reported.
      This is the first report of three mycotic aneurysms occurring in a young man with
      neurobrucellosis treated surgically.

PMID- 25396075
TI  - Usefulness of continuous suture using short-thread double-armed micro-suture for
      cerebral vascular anastomosis.
AB  - BACKGROUND: When microvascular anastomosis is performed in a deep, narrow
      operating field, securing space to throw knots is difficult. To simplify the
      procedure and avoid obstruction of the anastomosis, we use a continuous suturing
      with short-thread double-armed micro-suture. METHODS: Sixty-four patients (38
      cerebral revasculazation, 16 moyamoya disease, and 10 aneurysm surgery)
      undergoing microvaucular anastomosis were included. During anastomosis, a
      continuous suture was placed with short-thread double-armed micro-suture.
      RESULTS: During 64 microanastomosis procedures, 64 consecutive continuous sutures
      were performed with 1-year follow up. All patients showed patency of anastomosis
      with long-term follow up. CONCLUSIONS: This technique is especially useful for
      anastomosis in a deep, narrow surgical field, such as in superior cerebellar
      artery anastomosis.

PMID- 25396076
TI  - Aneurysmal bone cyst of the calcaneus.
AB  - Aneurysmal bone cysts (ABCs) are benign, non-neoplastic, expansile, vascular,
      locally destructive lesions. The lesion may arise de novo (65%) or secondarily
      (35%) in pre-existing benign or malignant lesions (giant cell tumor,
      osteoblastoma, chondroblastoma, angioma, and others). The calcaneus is a rare
      localization for ABC, comprising only 1.6% of the cases. In this paper, we
      present a case of a female patient with a 3-month history of heel pain that got
      worse and was accompanied by swelling and difficulty in walking. The magnetic
      resonance images of the postero-lateral calcaneus showed a contrast-enhanced
      cystic lesion located in the medullary cavity; exophytic portion of the tumor
      extended into the soft tissue causing distinctive cortical thinning.
      Heterogeneous hyperintense septae formations and blood level components were also
      detected. After correlation with pathology results, the lesion was diagnosed as
      an ABC. Since an ABC of the calcaneus is a rarely seen phenomenon, we present the
      radiologic findings in this case and a review of the literature. 

PMID- 25396077
TI  - Lesions of the Seminal Vesicles and their MRI Characteristics.
AB  - Over the past few decades, MRI of the prostate has made great strides in
      improving cancer detection and is being embraced by more clinicians each day.
      This article aims to review the imaging characteristics of common and uncommon,
      but consequential lesions involving the seminal vesicles (SV), as seen
      predominantly on MRI. Many of these findings are seen incidentally during imaging
      of the prostate. Anatomy and embryology of the SV will be described which will
      help illustrate the associations of abnormalities seen. Congenital, infectious,
      neoplastic, and tumor mimics will be explored in detail, with discussion on
      clinical presentation and treatment strategies. 

PMID- 25396078
TI  - Dermatopathology: An abridged compendium of words. A discussion of them and
      opinions about them. Part 6 (I-L).

PMID- 25396079
TI  - When all you have is a dermatoscope- start looking at the nails.
AB  - Pigmented and non-pigmented nail alterations are a frequent challenge for
      dermatologists. A profound knowledge of clinical and dermatoscopic features of
      nail disorders is crucial because a range of differential diagnoses and even
      potentially life-threatening diseases are possible underlying causes. Nail matrix
      melanocytes of unaffected individuals are in a dormant state, and, therefore,
      fingernails and toenails physiologically are non-pigmented. The formation of
      continuous, longitudinal pigmented streaks (longitudinal melanonychia) may either
      be caused by a benign activation of matrix melanocytes (e.g., as a result of
      trauma, inflammation, or adverse drug reactions) or by a true melanocytic
      proliferation (e.g., in a nevus or melanoma). In general, non-continuous nail
      alterations, affecting only limited parts of the nail apparatus, are most
      frequently of non-melanocytic origin. Important and common differential diagnoses
      in these cases are subungual hemorrhage or onychomycosis. In addition, foreign
      bodies, bacterial infections, traumatic injuries, or artificial discolorations of
      the nail unit may less frequently cause non-continuous nail alterations. Many
      systemic diseases that may also show involvement of the nails (e.g., psoriasis,
      atopic dermatitis, lichen planus, alopecia areata) tend to induce alterations in
      numerous if not all nails of the hands and feet. A similar extensive and
      generalized alteration of nails has been reported after treatment with a number
      of systemic drugs, especially antibiotics and cytostatics. Benign or malignant
      neoplasms that may also affect the nail unit include glomus tumor, Bowen's
      disease, squamous cell carcinoma, and rare collision tumors. This review aims to
      assist clinicians in correctly evaluating and diagnosing nail disorders with the
      help of dermatoscopy. 

PMID- 25396080
TI  - Epidermal multinucleated giant cells are not always a histopathologic clue to a
      herpes virus infection: multinucleated epithelial giant cells in the epidermis of
      lesional skin biopsies from patients with acantholytic dermatoses can
      histologically mimic a herpes virus infection.
AB  - BACKGROUND: Multinucleated giant cells in the epidermis can either be epithelial
      or histiocytic. Epithelial multinucleated giant cells are most often associated
      with herpes virus infections. PURPOSE: To review the histologic differential
      diagnosis of conditions with epithelial and histiocytic multinucleated giant
      cells-since multinucleated giant cells in the epidermis are not always
      pathognomonic of a cutaneous herpes virus infection-and to summarize dermatoses
      in which herpes virus infection has been observed to coexist. METHODS: Two
      individuals with acantholytic dermatoses whose initial lesional skin biopsies
      showed multinucleated epithelial giant cells suggestive of a herpes virus
      infection are reported. Using the PubMed database, an extensive literature search
      was performed on multinucleated giant cell (and epidermis, epithelial, and
      histiocytic) and herpes virus infection. Relevant papers were reviewed to
      discover the skin conditions with either multinucleated giant cells in the
      epidermis or coincident cutaneous herpes virus infection. RESULTS: Initial skin
      biopsies from patients with either pemphigus vulgaris or transient acantholytic
      dermatosis mimicked herpes virus infection; however, laboratory studies and
      repeat biopsies established the correct diagnosis of their acantholytic
      dermatosis. Hence, epidermal multinucleated giant cells are not always a
      histopathologic clue to a herpes virus infection. Indeed, epithelial
      multinucleated giant cells in the epidermis can be observed not only in the
      presence of infection (herpes virus), but also acantholytic dermatoses and tumors
      (trichoepithelioma and pleomorphic basal cell carcinoma). Histiocytic
      multinucleated giant cells in the epidermis can be observed in patients with
      either giant cell lichenoid dermatitis or lichen nitidus of the palms.
      CONCLUSIONS: Epithelial and histiocytic multinucleated giant cell can occur in
      the epidermis. Keratinocyte-derived multinucleated giant cells are most commonly
      associated with herpes virus infection; yet, they can also be observed in
      patients with skin tumors or acantholytic dermatoses. Cutaneous herpes simplex
      virus infection can coexist in association with other conditions such as
      acantholytic dermatoses, benign skin tumors, bullous disorders, hematologic
      malignancies, inflammatory dermatoses, and physical therapies. However, when a
      herpes virus infection is suspected based upon the discovery of epithelial
      multinucleated giant cells in the epidermis, but either the clinic presentation
      or lack of response to viral therapy or absence of confirmatory laboratory
      studies does not support the diagnosis of a viral infection, the possibility of a
      primary acantholytic dermatosis should be considered and additional lesional skin
      biopsies performed. Also, because hematoxylin and eosin staining is not the
      golden standard for confirmation of autoimmune bullous dermatoses, skin biopsies
      for direct immunofluorescence should be performed when a primary bullous
      dermatosis is suspected since the histopathology observed on hematoxylin and
      eosin stained sections can be misleading.

PMID- 25396081
TI  - Hailey-Hailey disease associated with herpetic eczema-the value of the Tzanck
      smear test.
AB  - BACKGROUND: Herpetic eczema is a herpetic superinfection of a preexisting skin
      disease. Hailey-Hailey disease is an autosomal dominant dermatosis that is
      clinically characterized by flaccid vesicles and rashes in intertriginous areas.
      The coexistence of those findings is a rare condition; only five cases have been
      published in literature. PURPOSE: To report the rare coexistence between Hailey
      Hailey disease and herpetic eczema and to highlight the importance of cytology
      for a quick diagnosis. CASE REPORT: A 38-year-old man had been diagnosed with
      Hailey-Hailey disease for 13 years. His condition evolved into what could be
      herpetic eczema, which was later confirmed by skin cytology and histopathology.
      The man showed remission in the infection after 10 days under treatment with
      acyclovir. CONCLUSION: Research on the concomitance of infection by the herpes
      virus must be performed in the exacerbations of Hailey-Hailey disease, and, in
      those situations, the quick diagnosis through skin cytology makes the early
      treatment possible.

PMID- 25396082
TI  - Disseminated gouty panniculitis: an unusual presentation of extensive cutaneous
      tophi.
AB  - Gouty panniculitis is a rare cutaneous illness characterized by the deposition of
      subcutaneous mono-sodium urate crystals with lobular panniculitis. Only a small
      number of cases with gouty panniculitis have been reported in the literature with
      unclear pathogenesis. In this article, we present a case of disseminated gouty
      panniculitis in the patient who had never been diagnosed of gout but revealed
      significant hyperuricemia at the time of diagnosis. 

PMID- 25396083
TI  - Generalized, pruritic skin eruption in an immunocompromised patient.

PMID- 25396084
TI  - The role of dermoscopy and digital dermoscopy follow-up in the clinical diagnosis
      of melanoma: clinical and dermoscopic features of 99 consecutive primary
      melanomas.
AB  - BACKGROUND: Early recognition is the most important intervention to improve
      melanoma prognosis. OBJECTIVE: To report the value of dermoscopy and digital
      dermoscopy in the clinical diagnosis of malignant melanoma (MM). METHODS:
      Retrospective analysis of 99 consecutive primary MMs diagnosed between 2010 and
      2013. The MMs were divided into 3 groups: 1) the MM was the reason for
      consultation (MMC), 2) the MM was detected during routine control of nevi (MMRC),
      and 3) the MM was detected due to changes observed during digital dermoscopy
      follow-up (MMDFU). Clinical, dermoscopic and histologic features were assessed.
      RESULTS: A total of 99 MMs were diagnosed in 89 patients (55% male) with a mean
      age of 50.8 (18-93) years. Of all the MMs, 35 were the reason for patient
      consultation (MMC), 52 were detected during routine control of nevi (MMRC) and 12
      were diagnosed due to changes observed with digital dermoscopy (MMDFU). On
      clinical examination, 74.2 % of MMC met the 4 ABCD criteria, while only 30.7 % of
      MMRC and 8.3 % of MMDFU. Most MMC were correctly classified as malignant
      according to dermoscopy, but 44.2% of MMRC and only 16.7% of MMDFU. 22.9% of MMC,
      50% of MMRC and 58.3% of MMDFU were in situ. Mean Breslow thickness was
      significantly lower in the MMDFU group (0.52 mm) than in the MMRC and MMDFU
      groups (0.77 and 1.43 mm respectively). CONCLUSIONS: The use of dermoscopy and
      digital dermoscopy allows the detection of MMs in early stages, even in the
      absence of specific criteria for malignancy.

PMID- 25396085
TI  - Comparison of dermatoscopic images of acral lentiginous melanoma and acral
      melanocytic nevus occurring on body weight-bearing areas.
AB  - BACKGROUND: Because body weight-bearing produces a shift in the horny layer,
      acral melanocytic nevus on the body weight-bearing area of the sole showed a
      regular fibrillar pattern (FP) due to slanting of the melanin columns in the
      horny layer. On the other hand, acral lentiginous melanoma (ALM) on the body
      weight-bearing area of the sole tended to show irregular fibrillar pattern
      showing rather structureless pigmentation instead of a parallel ridge pattern,
      which is due to the shift of the horny layer. OBJECTIVE: To elucidate the subtle
      difference between the regular FP of nevus and irregular FP in ALM. METHODS: In
      this study, the dermatoscopic features of five cases of ALM and five cases of
      acral melanocytic nevus on the weight-bearing area of the sole were compared.
      RESULTS: All the cases with nevi showed regular FP showing regular distribution
      of fibrils, whereas all the melanomas showed irregular distribution of fibrils
      and colors. Fibrils in nevi tended to be clear at the furrows and dim at the
      ridges. White fibrils corresponding to the eccrine ducts in the horny layer were
      more often present on the ridges in ALM, which showed negative FP. CONCLUSION:
      Differentiating between the regular and irregular FP, including negative FP,
      might be helpful for the discrimination of melanoma from nevus.

PMID- 25396086
TI  - Assessment of the colors of melanin pigment in acral compound nevus by using a
      novel dermoscopy technique with surgical light illumination and saturation
      analysis.

PMID- 25396087
TI  - A case of a superficial spreading melanoma in situ diagnosed via digital
      dermoscopic monitoring with high dynamic range conversion.
AB  - A 48-year-old woman presented with a 3 mm, pigmented macule at her first visit to
      our clinic. The macule, which showed complete symmetry and a typical network, was
      tentatively diagnosed as a Clark nevus; a 6-month follow-up was recommended, and
      the patient returned 7 months later. At the second visit, the lesion had enlarged
      to a diameter of 5 mm, and dermoscopy revealed that it had maintained its typical
      pigment network. At this point, evidence-based monitoring would have led to
      excision but the decision was made to continue monitoring. Owing to poor
      compliance, the patient went another 2 years without follow-up. When we assess
      small lesions, such as this, the usefulness of dermoscopy is apparent.
      Additionally, we examined the benefits and drawbacks of high dynamic range (HDR)
      conversion of the dermoscopy images and their helpfulness for inspecting small
      lesions. Although the delicate structures present in the lesion can be recognized
      by a dermoscopy expert and HDR image conversion has a capacity to highlight
      important structures, there is also a risk that HDR image conversion may mask
      some of the structural changes. However, a comparison of the original dermoscopy
      images with the HDR-converted images provides newly trained dermoscopists the
      opportunity to recognize new findings and to distinguish the differences in the
      findings between both the types of images. Therefore, such comparisons might be
      useful for obtaining an accurate diagnosis by using dermoscopy and HDR image
      conversion. 

PMID- 25396088
TI  - Dermoscopic findings in bowenoid papulosis: report of two cases.
AB  - Bowenoid papulosis (BP) corresponds to an in situ squamous cell carcinoma (SCC)
      located in the anogenital region. It is related to HPV, and presents with gray
      brown elevated papules or plaques. A biopsy is needed to confirm the diagnosis;
      however, dermoscopy may be useful to differentiate this disease from other
      conditions, such as genital warts, seborrheic keratosis and lichen planus. In
      this paper we describe the dermoscopic findings in two patients with this
      disease. 

PMID- 25396089
TI  - Dermatoscopic pattern of digital mucous cyst: report of three cases.
AB  - Digital mucous cysts are benign ganglion cysts of the digits typically located on
      the dorsal aspect of the interphalangeal joint and distal phalanx of the digits.
      Usually the clinical diagnosis is straightforward, though sometimes it may mimic
      other lesions and diagnosis becomes a challenge. We present a series of three
      digital mucous cysts with a repeatable dermoscopic pattern consisted of linear
      branched and serpentine vessels when no compression is applied and translucent
      aspect with white bright areas and loss of vascular pattern when compression is
      applied. 

PMID- 25396090
TI  - What is your diagnosis? A solitary purple papule on the arm.

PMID- 25396091
TI  - Dermatoscopy: A multicolored lesion on the forehead-Quiz Answer.

PMID- 25396092
TI  - Non-traditional melanoma prevention strategies in the young adult and adolescent
      population.

PMID- 25396093
TI  - A unifying approach to the clinical diagnosis of melanoma including "D" for
      "Dark" in the ABCDE criteria.
AB  - Current clinical approaches to melanoma diagnosis have not been associated with a
      decrease in mortality from this cancer. The components of the new approach
      presented are, first, a screening examination to look for any lesion that stands
      out because of being dark, different, or changing; second, when a single lesion
      is recognized to be of concern for any reason, that lesion is then evaluated in
      more detail utilizing the ABCDE criteria, with the "D" signifying "Dark" and not
      "6 mm Diameter" in this mnemonic; and, third, additional discussion of the "ugly
      duckling" sign and of the recognition of nodular melanomas. Since the Georgia
      Society of Dermatology and Dermatologic Surgery was the first state or national
      society to endorse this approach, I refer to it as the Georgia approach. 

PMID- 25396094
TI  - Vitiligo Extent Tensity Index (VETI) score: a new definition, assessment and
      treatment evaluation criteria in vitiligo.
AB  - Although skin is the largest organ of the body, there are no standardized
      reproducible methods for assessing severity of many skin diseases. Due to lack of
      consensus, methods of assessment and inexistence of precise scoring system, there
      is no application for vitiligo estimation in real practice. In this paper the
      author describes VETI score as a new treatment evaluation criteria and severity
      assessment method for vitiligo. This new tool, as does the PASI score in
      psoriasis, may be able to produce a constant and reproducible number and to help
      clinical research on vitiligo patients. Additionally it has a potential to be a
      source of any computed application for researchers working on vitiligo patients. 

PMID- 25396095
TI  - Diagnosis of ophthalmomyiasis externa by dermatoscopy.
AB  - Ophthalmomyiasis in humans caused by the larvae of the sheep nasal botfly
      (Oestrus ovis) and is a rare phenomenon in Israel. We describe the utilization of
      the dermatoscope as a diagnostic tool for the facilitation of early diagnosis of
      conjunctivitis due to the infestation of the eyes by the sheep nasal botfly in
      two patients. After the physical removal of the larvae with the help of a cotton
      swab applicator under a slit lamp examination and the topical use of antibiotics,
      the clinical symptoms improved within 1-2 days. Undoubtedly the dermatoscope
      played a crucial role leading to the definitive diagnosis and immediate
      therapeutic intervention. 

PMID- 25396096
TI  - Zosteriform cutaneous leishmaniasis.

PMID- 25396097
TI  - Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the
      GLACIER and VIKING Studies.
AB  - Most complex diseases have well-established genetic and non-genetic risk factors.
      In some instances, these risk factors are likely to interact, whereby their joint
      effects convey a level of risk that is either significantly more or less than the
      sum of these risks. Characterizing these gene-environment interactions may help
      elucidate the biology of complex diseases, as well as to guide strategies for
      their targeted prevention. In most cases, the detection of gene-environment
      interactions will require sample sizes in excess of those needed to detect the
      marginal effects of the genetic and environmental risk factors. Although many
      consortia have been formed, comprising multiple diverse cohorts to detect gene
      environment interactions, few robust examples of such interactions have been
      discovered. This may be because combining data across studies, usually through
      meta-analysis of summary data from the contributing cohorts, is often a
      statistically inefficient approach for the detection of gene-environment
      interactions. Ideally, single, very large and well-genotyped prospective cohorts,
      with validated measures of environmental risk factor and disease outcomes should
      be used to study interactions. The presence of strong founder effects within
      those cohorts might further strengthen the capacity to detect novel genetic
      effects and gene-environment interactions. Access to accurate genealogical data
      would also aid in studying the diploid nature of the human genome, such as
      genomic imprinting (parent-of-origin effects). Here we describe two studies from
      northern Sweden (the GLACIER and VIKING studies) that fulfill these
      characteristics.

PMID- 25396098
TI  - Mouse models of liver fibrosis mimic human liver fibrosis of different
      etiologies.
AB  - The liver has the amazing capacity to repair itself after injury; however, the
      same processes that are involved in liver regeneration after acute injury can
      cause serious consequences during chronic liver injury. In an effort to repair
      damage, activated hepatic stellate cells trigger a cascade of events that lead to
      deposition and accumulation of extracellular matrix components causing the
      progressive replacement of the liver parenchyma by scar tissue, thus resulting in
      fibrosis. Although fibrosis occurs as a result of many chronic liver diseases,
      the molecular mechanisms involved depend on the underlying etiology. Since
      studying liver fibrosis in human subjects is complicated by many factors, mouse
      models of liver fibrosis that mimic the human conditions fill this void. This
      review summarizes the general mouse models of liver fibrosis and mouse models
      that mimic specific human disease conditions that result in liver fibrosis.
      Additionally, recent progress that has been made in understanding the molecular
      mechanisms involved in the fibrogenic processes of each of the human disease
      conditions is highlighted.

PMID- 25396100
TI  - Clinical Management of Pediatric Genomic Testing.
AB  - As sequencing becomes integrated into clinical medicine, many complex ethical
      questions arise regarding the return of genomic information, especially in
      pediatrics. Issues center on the best interests of the child, particularly in
      return of information about adult-onset conditions. These include the child's
      future autonomous decision-making and access to knowledge about treatable
      conditions, the child in the family unit, and benefit to family members of
      learning information which could impact them personally. This article first
      discusses the framework for returning genomic information, and then ethical
      issues regarding return of results. Finally it discusses potential harms and
      benefits, while recognizing that little is known about what these actually are. A
      new era of genomic information is in its infancy; handling genomic information in
      a way that provides patients and their families with knowledge that is helpful
      without causing distress is the greatest challenge.

PMID- 25396099
TI  - Noninvasive Biomarkers of Liver Fibrosis: Clinical Applications and Future
      Directions.
AB  - Chronic liver disease is a significant cause of morbidity and mortality
      worldwide. Current strategies for assessing prognosis and treatment rely on
      accurate assessment of disease stage. Liver biopsy is the gold standard for
      assessing fibrosis stage but has many limitations. Noninvasive biomarkers of
      liver fibrosis have been extensively designed, studied, and validated in a
      variety of liver diseases. With the advent of direct acting antivirals and the
      rise in obesity-related liver disease, there is a growing need to establish these
      noninvasive methods in the clinic. In addition, it has become increasingly clear
      over the last few years that noninvasive biomarkers can also be used to monitor
      response to antifibrotic therapies and predict liver outcomes, including
      hepatocellular carcinoma development. This review highlights the most well
      established noninvasive biomarkers to-date, with a particular emphasis on serum
      and imaging-based methodologies.

PMID- 25396101
TI  - Cervical spinal cord dimensions and clinical outcomes in adults with klippel-feil
      syndrome: a comparison with matched controls.
AB  - Study Design Retrospective case-control study. Objectives To confirm the fact
      that spinal cord dimensions are smaller in adults with Klippel-Feil syndrome
      (KFS) than in pediatric patients with KFS and to compare the clinical
      characteristics and outcomes of neurologic complications in patients with KFS
      with matched controls. Methods We performed an independent 1:2 case-control
      retrospective radiographic and chart review of a consecutive series of adults
      with KFS who underwent surgical intervention. The control group consisted of
      consecutive non-KFS surgical patients. Patients were matched in 1:2 case-control
      manner. Their charts were reviewed and the clinical characteristics were
      compared. Axial T2-weighted magnetic resonance imaging (MRI) was used to measure
      the anteroposterior and mediolateral axial spinal cord and spinal canal at the
      operative levels and measurements were compared. Results A total of 22 patients
      with KFS and 44 controls were identified. The KFS group had a tendency of more
      myeloradiculopathy, and the control group had a tendency toward more
      radiculopathy. Both tendencies, however, were not significantly different. MRIs
      of 10 patients from the KFS group and 22 controls were available. There was no
      difference in the area of both spinal cord and canal at the operative levels.
      Conclusion Contrary to the finding in previous reports on pediatric patients,
      there were no differences between KFS and well-matched control groups in terms of
      age of onset, presentation, revision rate, complication rate, surgical outcome,
      and cross-sectional spinal cord and canal dimensions at the operative level. 

PMID- 25396102
TI  - Magnetic resonance imaging of the cervical, thoracic, and lumbar spine in
      children: spinal incidental findings in pediatric patients.
AB  - Study Design Retrospective case series. Objective To determine the rate of spinal
      incidental findings on magnetic resonance imaging (MRI) of the cervical,
      thoracic, and lumbar spine in the pediatric population. Methods We reviewed MRI
      imaging of the neuraxial spine in patients less than 18 years of age and
      documented abnormal spinal findings. We then reviewed the charts of these
      patients to determine the reason for ordering the study. Those who presented with
      pain were considered symptomatic. Those who had no presenting complaint were
      considered asymptomatic. The data were analyzed to break down the rate of spinal
      incidental findings in the cervical, thoracic, and lumbar spine, respectively.
      Results Thirty-one of the 99 MRIs had positive findings, with the most common
      being disk protrusion (51.6%). Spinal incidental findings were most common in the
      lumbar spine (9.4%) versus the cervical spine (8%) or thoracic spine (4.7%). In
      this group, Schmorl nodes and disk protrusion were the two most common findings
      (37.5% each). Other spinal incidental findings included a vertebral hemangioma
      and a Tarlov cyst. In the thoracic spine, the only spinal incidental finding was
      a central disk protrusion without spinal cord or nerve root compression.
      Conclusion MRI is a useful modality in the pediatric patient with scoliosis or
      complaints of pain, but the provider should remain cognizant of the potential for
      spinal incidental findings. 

PMID- 25396103
TI  - Lumbosacral transitional vertebrae and its prevalence in the Australian
      population.
AB  - Study Design Retrospective cohort study. Objective Lumbosacral transitional
      vertebrae (LSTV) are a common congenital anomaly, and they can be accurately
      identified on anteroposterior (AP) radiographs of the lumbosacral spine. This
      study attempts to determine the prevalence of this congenital anomaly and to
      increase awareness among all clinicians to reduce the risk of surgical and
      procedural errors in patients with LSTV. Methods A retrospective review of 5,941
      AP and lateral lumbar radiographs was performed. Transitional vertebrae were
      identified and categorized under the Castellvi classification. Results The
      prevalence of LSTV in the study population was 9.9%. Lumbarized S1 and sacralized
      L5 were seen in 5.8 and 4.1% of patients, respectively. Conclusion LSTV are a
      common normal variant and can be a factor in spinal surgery at incorrect levels.
      It is essential that all clinicians are aware of this common congenital anomaly. 

PMID- 25396104
TI  - Lumbar disk herniation surgery: outcome and predictors.
AB  - Study Design A retrospective cohort study. Objectives To determine the outcome
      and any differences in the clinical results of three different surgical methods
      for lumbar disk herniation and to assess the effect of factors that could predict
      the outcome of surgery. Methods We evaluated 148 patients who had operations for
      lumbar disk herniation from March 2006 to March 2011 using three different
      surgical techniques (laminectomy, microscopically assisted percutaneous
      nucleotomy, and spinous process osteotomy) by using Japanese Orthopaedic
      Association (JOA) Back Pain Evaluation Questionnaire, Resumption of Activities of
      Daily Living scale and changes of visual analog scale (VAS) for low back pain and
      radicular pain. Our study questionnaire addressed patient subjective satisfaction
      with the operation, residual complaints, and job resumption. Data were analyzed
      with SPSS version 16.0 (SPSS, Inc., Chicago, Illinois, United States).
      Statistical significance was set at 0.05. For statistical analysis, chi-square
      test, Mann-Whitney U test, Kruskal-Wallis test, and repeated measure analysis
      were performed. For determining the confounding factors, univariate analysis by
      chi-square test was used and followed by logistic regression analysis. Results
      Ninety-four percent of our patients were satisfied with the results of their
      surgeries. VAS documented an overall 93.3% success rate for reduction of
      radicular pain. Laminectomy resulted in better outcome in terms of JOA Back Pain
      Evaluation Questionnaire. The outcome of surgery did not significantly differ by
      age, sex, level of education, preoperative VAS for back, preoperative VAS for
      radicular pain, return to previous job, or level of herniation. Conclusion
      Surgery for lumbar disk herniation is effective in reducing radicular pain
      (93.4%). All three surgical approaches resulted in significant decrease in
      preoperative radicular pain and low back pain, but intergroup variation in the
      outcome was not achieved. As indicated by JOA Back Pain Evaluation Questionnaire
      Low Back Pain (JOABPQ-LBP) and lumbar function functional scores, laminectomy
      achieved significantly better outcome compared with other methods. It is worth
      mentioning that relief of radicular pain was associated with subjective
      satisfaction with the surgery among our study population. Predictive factors for
      ineffective surgical treatment for lumbar disk herniation were female sex and
      negative preoperative straight leg raising. Age, level of education, and
      preoperative VAS for low back pain were other factors that showed prediction
      power. 

PMID- 25396106
TI  - Modified posterior lumbar interbody fusion for radiculopathy following healed
      vertebral collapse of the middle-lower lumbar spine.
AB  - Study Design Retrospective study. Objectives Lumbar radiculopathy is rarely
      observed in patients who have achieved bony healing of vertebral fractures in the
      middle-lower lumbar spine. The objectives of the study were to clarify the
      clinical features of such radiculopathy and to evaluate the preliminary outcomes
      of treatment using a modified posterior lumbar interbody fusion (PLIF) procedure.
      Methods Fourteen patients with at least 2-year follow-up were enrolled in this
      study. The radiologic and clinical features of radiculopathy were retrospectively
      reviewed. As part of our modified PLIF procedure, a bone block was laid on
      chipped bone to fill the cavity of the fractured end plate and to flatten the
      cage-bone interface. Results The morphologic features of spinal deformity in our
      patients typically consisted of the intradiscal vacuum phenomenon,
      spondylolisthesis, and a retropulsed intervertebral disk with a vertebral rim in
      the damaged segment. Cranial end plate fracture resulted in radiculopathy of the
      traversing nerve roots due to lateral recess stenosis. On the other hand, caudal
      end plate fracture led to unilateral radiculopathy of the exiting nerve root due
      to foraminal stenosis. The mean recovery rate based on the Japanese Orthopaedic
      Association score was 65.0%. Solid fusion was achieved in all but one case.
      Conclusions Because of severe deterioration of the anterior column following end
      plate fracture, the foraminal zone must be decompressed in caudal end plate
      fractures. The modified PLIF procedure yielded satisfactory clinical outcomes due
      to anterior reconstruction and full decompression for both foraminal and lateral
      recess stenoses. 

PMID- 25396105
TI  - Quality-of-Life Outcomes following Thoracolumbar and Lumbar Fusion with and
      without the Use of Recombinant Human Bone Morphogenetic Protein-2: Does
      Recombinant Human Bone Morphogenetic Protein-2 Make a Difference?
AB  - Design Retrospective study. Objectives (1) To investigate the quality-of-life
      (QOL) outcomes in the population undergoing lumbar spine surgery with versus
      without recombinant human bone morphogenetic protein-2 (rhBMP-2); (2) to
      determine QOL outcomes for those patients who experience postoperative
      complications; and (3) to identify the effect of patient characteristics on
      postoperative QOL outcomes. Methods A retrospective review of QOL questionnaires,
      including the Patient Health Questionnaire-9, Patient Disability Questionnaire
      (PDQ), EuroQol-5D (EQ-5D), and quality of life-year (QALY), was performed for all
      patients who underwent thoracolumbar and lumbar fusion surgery with versus
      without rhBMP-2 between March 2008 and September 2010. Individual preoperative
      and postoperative QOL data were compared for each patient. Demographic factors
      and complications were reviewed. Results We identified 266 patients, including 60
      with and 206 without rhBMP-2. Questionnaires were completed an average of 10.3 +/
      5 months after surgery. For all measures, average scores improved
      postoperatively compared with preoperatively. No differences in postoperative QOL
      outcomes were identified between the rhBMP-2 and the control cohorts. Median
      annual household income was positively associated with EQ-5D and QALY. Compared
      with those without, patients with postoperative complications had fewer QOL
      improvements. Conclusions There was no difference in QOL outcomes in the rhBMP-2
      compared with the control group. Socioeconomic status and postoperative
      complications affected QOL outcomes following surgery. The QOL questionnaires
      provide the clinician with information regarding the patients' self-perceived
      well-being and can be helpful in the selection of surgical candidates and for
      understanding the effectiveness of a given surgical procedure. 

PMID- 25396107
TI  - One-stage open reduction of an old cervical subluxation: case report.
AB  - Study Design Case report. Objective The recommended treatment of cervical
      subluxation is currently closed or open reduction. These treatments are better
      accomplished in the acute setting, when muscular and ligamentous laxity allows
      the required maneuvers to realign the dislocated segments. However, subsets of
      patients are still being treated subacutely. The majority of the literature
      addressing subacute subluxations reports treatment through "front and back"
      approaches, many of them performed in two, three, or even four stages. Other
      authors recommend days or weeks of traction to reduce the subluxation, followed
      by anterior or posterior approaches. Herein, we present a one-stage open
      posterior surgical treatment of a 2-month standing C5-C6 subluxation with "jumped
      facets," describing a useful technique to reduce these challenging cases without
      the need of traction or multistage procedures. Methods After opening and exposing
      the posterior elements, we performed a wide C5-6 bilateral foraminotomy; we then
      put lateral mass screws and rods from C4 to C6. Resembling the technique used in
      the reduction of high-grade lumbar spondylolisthesis, we used a rod reducer to
      bring back the C5 screw head toward the rod, thus realigning the lateral mass
      screw heads and reducing the subluxation. Results No changes were observed in the
      motor evoked or somatosensory potentials during this maneuver. Following an
      uneventful procedure, the patient was transferred to the postanesthetic care unit
      and discharged 3 days later. Conclusions This open single-stage posterior
      approach dramatically reduces operating time. This technique could be added into
      the decision-making armamentarium for cases without disk herniation. 

PMID- 25396108
TI  - Foix-alajouanine syndrome presenting as acute cauda equina syndrome: a case
      report.
AB  - Study Design Case report. Objective Present a case of Foix-Alajouanine syndrome
      that presented as acute cauda equina syndrome and discuss the pathophysiology and
      management. Methods An adult male patient developed sudden onset of back pain and
      leg pain with weakness of the lower limbs and bladder/bowel dysfunction typical
      of cauda equina syndrome. Emergency magnetic resonance imaging revealed no
      compressive lesion in the spine but showed tortuous flow voids and end-on blood
      vessels in the peridural region suggesting spinal arteriovenous malformation
      resulting in Foix-Alajouanine syndrome. Results The case was managed by
      endovascular embolization with excellent results. The pathophysiology, imaging
      features, management, and literature review of the syndrome is discussed.
      Conclusion The authors conclude that this condition may be an important
      differential diagnosis for cauda equina syndrome. 

PMID- 25396109
TI  - Anterior-only Partial Sacrectomy for en bloc Resection of Locally Advanced Rectal
      Cancer.
AB  - Study Design Case report. Objective The usual procedure for partial sacrectomies
      in locally advanced rectal cancer combines a transabdominal and a posterior
      sacral route. The posterior approach is flawed with a high rate of complications,
      especially infections and wound-healing problems. Anterior-only approaches have
      indirectly been mentioned within long series of rectal cancer surgery. We
      describe a case of partial sacrectomy for en bloc resection of a locally advanced
      rectal cancer with invasion of the low sacrum through a combined transabdominal
      and perineal approach without any posterior incision. Methods Through a midline
      laparotomy, the tumor was dissected and the sacral osteotomy was performed. Once
      the sacrum was mobile, the muscular attachments to its posterior wall were cut
      through the perineal approach. This latter route was also used to remove the
      whole specimen. Results The postoperative period was uneventful in terms of
      infection and wound healing, but the patient developed right foot dorsiflexion
      paresis that completely disappeared in 1 month. Resection margins were negative.
      After a follow-up of 18 months, the patient has no local recurrence but presented
      lung and liver metastases. Conclusion In cases of rectal cancer involving the low
      sacrum, the combination of a transabdominal and a perineal route to carry out the
      partial sacrectomy is a feasible approach that avoids changes of surgical
      positioning and the morbidity related to posterior incisions. This strategy
      should be considered when deciding on undertaking partial sacrectomy in locally
      advanced rectal cancer. 

PMID- 25396110
TI  - Optimal duration of conservative management prior to surgery for cervical and
      lumbar radiculopathy: a literature review.
AB  - Study Design Literature review. Objective Since the 1970s, spine surgeons have
      commonly required 6 weeks of failed conservative treatment prior to considering
      surgical intervention for various spinal pathologies. It is unclear, however, if
      this standard has been validated in the literature. The authors review the
      natural history, outcomes, and cost-effectiveness studies relating to the current
      standard of 6 weeks of nonoperative care prior to surgery for patients with
      spinal pathologies. Methods A systematic Medline search from 1953 to 2013 was
      performed to identify natural history, outcomes, and cost-effectiveness studies
      relating to the optimal period of conservative management prior to surgical
      intervention for both cervical and lumbar radiculopathy. Demographic information,
      operative indications, and clinical outcomes are reviewed for each study. Results
      A total of 5,719 studies were identified; of these, 13 studies were selected for
      inclusion. Natural history studies demonstrated that 88% of patients with
      cervical radiculopathy and 70% of patients with lumbar radiculopathy showed
      improvement within 4 weeks following onset of symptoms. Outcomes and cost
      effectiveness studies supported surgical intervention within 8 weeks of symptom
      onset for both cervical and lumbar radiculopathy. Conclusions There are limited
      studies supporting any optimal duration of conservative treatment prior to
      surgery for cervical and lumbar radiculopathy. Therefore, evidence-based
      conclusions cannot be made. Based on the available literature, we suggest that an
      optimal timing for surgery following cervical radiculopathy is within 8 weeks of
      onset of symptoms. A shorter period of 4 weeks may be appropriate based on
      natural history studies. Additionally, we found that optimal timing for surgery
      following lumbar radiculopathy is between 4 and 8 weeks. A prospective study is
      needed to explicitly identify the optimal duration of conservative therapy prior
      to surgery so that costs may be reduced and patient outcomes improved. 

PMID- 25396111
TI  - Fixed sagittal plane imbalance.
AB  - Study Design Literature review. Objective To discuss the evaluation and
      management of fixed sagittal plane imbalance. Methods A comprehensive literature
      review was performed on the preoperative evaluation of patients with sagittal
      plane malalignment, as well as the surgical strategies to address sagittal plane
      deformity. Results Sagittal plane imbalance is often caused by de novo scoliosis
      or iatrogenic flat back deformity. Understanding the etiology and magnitude of
      sagittal malalignment is crucial in realignment planning. Objective parameters
      have been developed to guide surgeons in determining how much correction is
      needed to achieve favorable outcomes. Currently, the goals of surgery are to
      restore a sagittal vertical axis < 5 cm, pelvic tilt < 20 degrees, and lumbar
      lordosis equal to pelvic incidence +/- 9 degrees. Conclusion Sagittal plane
      malalignment is an increasingly recognized cause of pain and disability.
      Treatment of sagittal plane imbalance varies according to the etiology, location,
      and severity of the deformity. Fixed sagittal malalignment often requires complex
      reconstructive procedures that include osteotomy correction. Reestablishing
      harmonious spinopelvic alignment is associated with significant improvement in
      health-related quality-of-life outcome measures and patient satisfaction. 

PMID- 25396112
TI  - Steps for Improving Physical Activity Orientation Among Health-care Providers of
      Older Cardiovascular Patients.
AB  - Attaining appropriate levels of physical activity can have many potential
      physiological and psychological benefits in older adults with cardiovascular
      disease. However, these individuals often report low levels of physical activity
      and high levels of sedentary behavior. Older adults encounter many potential
      "barriers" to physical activity, but numerous studies have demonstrated the
      ability to positively influence this important health behavior using well
      established behavior change theories and models. The information provided in this
      review is directed at health-care providers who have the potential to impact
      physical activity behaviors during regular, often brief, clinical interactions.
      In addition to providing the latest physical activity recommendations, this
      update will provide a brief summary of some of the more widely used behavioral
      skills and strategies for promoting physical activity in older adults with
      cardiovascular disease.

PMID- 25396113
TI  - Minority Underrepresentation in Academia: Factors Impacting Careers of Surgery
      Residents.
AB  - BACKGROUND: Underrepresentation of minorities within academic surgery is an ever
      present problem with a profound impact on healthcare. The factors influencing
      surgery residents to pursue an academic career have yet to be formally
      investigated. We sought to elucidate these factors, with a focus on minority
      status. METHODS: A web-based questionnaire was sent to all administered to all
      ACGME-accredited general surgery programs in the United States. The main outcome
      was the decision to pursue a fully academic versus non-academic career.
      Multivariable logistic regression was used to identify characteristics impacting
      career choice. RESULTS: Of the 3,726 residents who received the survey, a total
      of 1,217 residents completed it - a response rate of 33%. Forty-seven percent
      planned to pursue non-academic careers, 35% academic careers, and 18% were
      undecided. There was no association between underrepresented minority status and
      academic career choice (Odds Ratio = 1.0, 95% Confidence Interval 0.6 - 1.6).
      Among all residents, research during training (OR=4.0, 95% CI 2.7-5.9),
      mentorship (OR=2.1, 95% CI 1.6-2.9), and attending a residency program requiring
      research (OR=2.3, 95% CI 1.5-3.4) were factors associated with choosing an
      academic career. When the analysis was performed among only senior residents
      (i.e., 4th and 5th year residents), a debt burden >$150,000 was associated with
      choosing a non-academic career (OR=0.4, 95% CI 0.1-0.9). CONCLUSIONS:
      Underrepresented minority status is not associated with career choice.
      Intentional recruitment of minorities into research-oriented training programs,
      increased mentorship and research support among current minority residents, and
      improved financial options for minorities may increase the number choosing an
      academic surgical career.

PMID- 25396115
TI  - How gesture works to change our minds.
AB  - When people talk, they gesture. We now know that these gestures are associated
      with learning-they can index moments of cognitive instability and reflect
      thoughts not yet found in speech. But gesture has the potential to do more than
      just reflect learning-it might be involved in the learning process itself. This
      review focuses on two non-mutually exclusive possibilities: (1) The gestures we
      see others produce have the potential to change our thoughts. (2) The gestures
      that we ourselves produce have the potential to change our thoughts, perhaps by
      spatializing ideas that are not inherently spatial. The review ends by exploring
      the mechanisms responsible for gesture's impact on learning, and by highlighting
      ways in which gesture can be effectively used in educational settings.

PMID- 25396114
TI  - The home physical activity environment and adolescent BMI, physical activity and
      TV viewing: Disparities across a diverse sample.
AB  - OBJECTIVE: Characteristics of the home and family have been associated with
      adolescents' BMI and physical and sedentary activity, but few studies have
      examined how these characteristics vary across ethnic/racial groups. This study
      explores whether recommendations for activity promotion are equally relevant to
      different adolescent populations. DESIGN: Participants included 2,374 adolescents
      and their parent(s), recruited through 20 public schools in Minneapolis/St. Paul,
      MN in 2009-2010. Ethnic/racial groups included African American, Asian (primarily
      Hmong), East African, Hispanic, Native American, White, and mixed/other race.
      Linear regression analysis modeled adolescents' BMI z-scores and physical and
      sedentary activity based on six measures of the family/home activity environment,
      adjusted for covariates. Interactions of ethnicity/race and family/home
      environment were tested. RESULTS: All six family/home environment measures varied
      significantly across ethnicity/race. Family/home variables were significantly
      associated with adolescent physical activity and TV viewing in the expected
      directions, and these relationships were consistent across ethnic/racial groups
      in two-thirds of the models. However, in one-third of the cases, these
      associations were modified by ethnicity/race. For example, home access to a
      greater number of media devices was significantly associated with more TV viewing
      (beta=.40, p=.015) only among White youth. CONCLUSION: Health promotion
      recommendations for adolescent physical activity are largely relevant across
      ethnic/racial groups. However, given differences found in the family/home
      environments of adolescents, cultural sensitivity is recommended in discussing
      these issues, and tailored recommendations may be appropriate for select groups
      or behaviors. Further mixed methods research is warranted to help identify key
      messages for specific groups.

PMID- 25396116
TI  - The Peltzman effect and compensatory markers in medicine.
AB  - Unintended consequences of health care interventions are unavoidable. For
      example, computerized order entry systems, implemented to reduce prescription
      errors, catalyze novel errors of their own, with providers unexpectedly relying
      on these systems to provide default dosing information rather than locating
      appropriate treatment guidelines. We argue that unintended behavioral responses
      by patients and physicians to health care interventions may explain why certain
      health care interventions that seem logical and foolproof fail to demonstrate
      real-world benefits. We argue that compensatory markers which measure behavioral
      responses in clinical trials should be implemented to better understand why real
      world benefits fail to materialize.

PMID- 25396117
TI  - Genome sequencing and annotation of Afipia septicemium strain OHSU_II.
AB  - We report the 5.1 Mb noncontiguous draft genome of Afipia septicemium strain
      OHSU_II, isolated from blood of a female patient. The genome consists of
      5,087,893 bp circular chromosome with no identifiable autonomous plasmid with a G
      + C content of 61.09% and contains 4898 protein-coding genes and 49 RNA genes
      including 3 rRNA genes and 46 tRNA genes.

PMID- 25396118
TI  - Identification of Biomarkers in Breast Cancer by Gene Expression Profiling Using
      Human Tissues.
AB  - Breast cancer is the second leading cause of death by cancer in women. To
      identify biomarkers with potential diagnostic and therapeutic utilities in breast
      cancer, gene expression profiling from real patient tissues were used to discover
      significantly deregulated genes out of 50,739 genes of human transcriptome. Total
      RNAs were extracted, and the gene expression profiles of 32 cancerous and normal
      tissues were established using Agilent gene expression microarray technology. The
      results were analyzed with Agilent GeneSpring 12.6 software. Here we provide
      detailed experimental methods and analysis for the microarray data, which have
      been deposited into Gene Expression Omnibus (GEO) under GSE57297.

PMID- 25396119
TI  - Nuclear factor kappaB represses the expression of latent membrane protein 1 in
      Epstein-Barr virus transformed cells.
AB  - AIM: To investigate the role of nuclear factor kappaB (NF-kappaB) in the
      regulation of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) in EBV
      transformed cells. METHODS: LMP1 expression was examined in EBV transformed human
      B lymphocytes with modulation of NF-kappaB activity. RESULTS: EBV infection is
      associated with several human cancers. EBV LMP1 is required for efficient
      transformation of adult primary B cells in vitro, and is expressed in several
      pathogenic stages of EBV-associated cancers. Regulation of EBV LMP1 involves both
      viral and cellular factors. LMP1 activates NF-kappaB signaling pathway that is a
      part of the EBV transformation program. However, the relation between NF-kappaB
      and LMP1 expression is not well established yet. In this report, we found that
      blocking the NF-kappaB activity by Inhibitor of kappaB stimulated LMP1
      expression, while the overexpression of NF-kappaB repressed LMP1 expression in
      EBV-transformed IB4 cells. In addition, LMP1 repressed its own promoter
      activities in reporter assays, and the repression was associated with the
      activation of NF-kappaB. Moreover, NF-kappaB alone is sufficient to repress LMP1
      promoter activities. CONCLUSION: Our data suggest LMP1 may repress its own
      expression through NF-kappaB in EBV transformed cells and shed a light on LMP1
      regulation during EBV transformation.

PMID- 25396120
TI  - Substrate specificity of avian influenza H5N1 neuraminidase.
AB  - AIM: To characterise neuraminidase (NA) substrate specificity of avian influenza
      H5N1 strains from humans and birds comparing to seasonal influenza virus.
      METHODS: Avian influenza H5N1 strains from humans and birds were recruited for
      characterising their NA substrate specificity by using a modified commercial
      fluorescence Amplex Red assay. This method can identify the preference of
      alpha2,6-linked sialic acid or alpha2,3-linked sialic acid. Moreover, to avoid
      the bias of input virus, reverse genetic virus using NA gene from human isolated
      H5N1 were generated and used to compare with the seasonal influenza virus.
      Lastly, the substrate specificity profile was further confirmed by high
      performance liquid chromatography (HPLC) analysis of the enzymatic product.
      RESULTS: The H5N1 NA showed higher activity on alpha2,3-linked sialic acid than
      alpha2,6-linked (P < 0.0001). To compare the NA activity between the H5N1 and
      seasonal influenza viruses, reverse genetic viruses carrying the NA of H5N1
      viruses and NA from a seasonal H3N2 virus was generated. In these reverse genetic
      viruses, the NA activity of the H5N1 showed markedly higher activity against
      alpha2,3-linked sialic acid than that of the H3N2 virus, whereas the activities
      on alpha2,6-linkage were comparable. Interestingly, NA from an H5N1 human isolate
      that was previously shown to have heamagglutinin (HA) with dual specificity
      showed reduced activity on alpha2,3-linkage. To confirm the substrate specificity
      profile, HPLC analytic of enzymatic product was performed. Similar to Amplex red
      assay, H5N1 virus showed abundant preference on alpha2,3-linked sialic acid.
      CONCLUSION: H5N1 virus maintains the avian specific NA and NA changes may be
      needed to accompany changes in HA receptor preference for the viral adaptation to
      humans.

PMID- 25396121
TI  - The case for case reports.

PMID- 25396122
TI  - Side-effects of topical steroids: A long overdue revisit.
AB  - The introduction of topical steroids (TS) of varying potency have rendered the
      therapy of inflammatory cutaneous disorders more effective and less time
      consuming. However the usefulness of these has become a double edged sword with
      constantly rising instances of abuse and misuse leading to serious local,
      systemic and psychological side effects. These side effects occur more with TS of
      higher potency and on particular areas of the body like face and genitalia. The
      article reviews the side effects of TS with special mention about peadiatric age
      group, also includes the measures for preventing the side effects. 

PMID- 25396124
TI  - Misuse of topical corticosteroids: A clinical study of adverse effects.
AB  - BACKGROUND: Misuse of topical corticosteroids is a widespread phenomenon among
      young people in India, especially women. The practice is associated with
      significant adverse effects and poor awareness of these effects among the general
      public. AIM: This study was conducted to examine the misuse and adverse effects
      of topical corticosteroids among the people in Bastar region in Chhattisgarh
      state of India. MATERIALS AND METHODS: Data collected from patients presenting
      with at least one of the adverse effects of topical corticosteroids as the chief
      complaint, from November 2010 to October 2011. RESULTS: Out of the 6723 new
      patients, 379 (5.63%) had presented with misuse and adverse effects of topical
      corticosteroids, of whom 78.89% were females. More than 65% of the patients were
      in the age group 10-29 years. The main reason for using the topical
      corticosteroids was to lighten skin colour and treat melasma and suntan. Acne
      (37.99%) and telangiectasia (18.99%) were the most common adverse effects noted.
      CONCLUSIONS: Misuse of topical corticosteroids has a huge impact on
      dermatological practice, leading to a significant proportion of visits to the
      dermatologist. This hydra-headed problem needs multi-dimensional interventions,
      involving educational, legal and managerial approaches with cooperation from
      different sectors of society.

PMID- 25396123
TI  - Melasma update.
AB  - Melasma is an acquired pigmentary disorder characterized by symmetrical
      hyperpigmented macules on the face. Its pathogenesis is complex and involves the
      interplay of various factors such as genetic predisposition, ultraviolet
      radiation, hormonal factors, and drugs. An insight into the pathogenesis is
      important to devise treatment modalities that accurately target the disease
      process and prevent relapses. Hydroquinone remains the gold standard of treatment
      though many newer drugs, especially plant extracts, have been developed in the
      last few years. In this article, we review the pathogenetic factors involved in
      melasma. We also describe the newer treatment options available and their
      efficacy. We carried out a PubMed search using the following terms "melasma,
      pathogenesis, etiology, diagnosis, treatment" and have included data of the last
      few years. 

PMID- 25396125
TI  - A study of the prevalence of methicillin-resistant Staphylococcus aureus in
      dermatology inpatients.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of
      increased morbidity and mortality in debilitated and immunocompromised patients.
      AIMS AND OBJECTIVES: To study the prevalence of MRSA among dermatology inpatients
      and elucidate its predisposing factors and antibiotic sensitivity pattern.
      MATERIALS AND METHODS: This prospective study involved all the inpatients in the
      dermatology ward with suspected bacterial infections, both primary and secondary.
      Gram's stain, pus culture, and antibiotic sensitivity were the main tests done.
      RESULTS: There were 61 patients in this study, with 36 males (59%) and 25 females
      (41%). The age group maximally affected was 41-50 years (21.6%). Vesiculobullous
      disorders (22, 36.1%) and eczemas (16, 26.2%) were the commonest dermatoses with
      secondary infection. Extremities (72.1%) and the trunk (26.2%) were the commonest
      sites involved. Diabetes mellitus (DM) was the commonest systemic illness
      (11.5%). Staphylococcus aureus was the commonest isolate, grown in 52 patients
      (85.2%) of whom 16 (30.80%) were MRSA positive. MRSA constituted 22.2% of the
      total bacterial isolates. All the MRSA isolates (100%) were resistant to
      cloxacillin and oxacillin, while all the isolates (100%) were sensitive to
      vancomycin and linezolid. CONCLUSIONS: The prevalence of MRSA in this study was
      high. It was most commonly seen in patients with vesiculobullous disorders. A
      high sensitivity of MRSA was found to amikacin. There was no relation between
      prolonged antibiotic therapy and MRSA in this study.

PMID- 25396126
TI  - Evaluation of state-run STI/RTI clinics in the state of Haryana, India through a
      supportive supervision approach.
AB  - INTRODUCTION: Sexually transmitted infections (STIs) are an important public
      health problem because of their adverse effects on reproductive health of men and
      women. About 5% of adult population in India suffers from STIs. To tackle this
      issue the government has set up reproductive tract infection (RTI) clinics across
      the country. AIMS: To assess the effect of supportive supervision on the quality
      of services provided in STI/RTI clinics in the state of Haryana, India. SETTINGS
      AND DESIGN: Selected state-run STI/RTI clinics, facility-based pre- and post
      evaluation study. MATERIAL AND METHODS: Sixteen STI/RTI clinics were selected for
      the study, including six from government facilities and 10 from targeted
      intervention sites across five districts of Haryana. From each of the selected
      sites one physician in-charge was interviewed twice with an interval of 2-3
      months using pretested formats. Scores were given in selected domains of STI/RTI
      management for each visit and the improvement was assessed. STATISTICAL ANALYSIS:
      Wilcoxon signed rank test. RESULTS: A total of 16 physicians one from each site
      were interviewed. Improvement in mean score of the physicians for knowledge about
      STI/RTI was 3.6 points. Similarly for skills score, which measured the
      physicians' skill in various domains of running STI/RTI clinics, the mean
      improvement was 3.1 points. Both the improvements were statistically significant
      (P < 0.001). CONCLUSIONS: Supportive supervision proved to be a useful tool for
      monitoring and improving the quality of services provided by the STI/RTI clinics.

PMID- 25396127
TI  - High prevalence of syphilis among street-based female sex workers in Nanchang,
      China.
AB  - BACKGROUND: Female sex workers (FSWs) play a critical role in the heterosexual
      transmission of human immunodeficiency virus (HIV)/sexually transmitted
      infections (STIs) in China. Several studies reported that street-based FSWs have
      higher risk behaviors than establishment-based FSWs. Therefore, street-based FSWs
      should be specifically targeted for HIV and STIs intervention programs.
      OBJECTIVES: This study aims to investigate the prevalence rates and risk factors
      of HIV and syphilis among FSWs in Nanchang, China. MATERIALS AND METHODS: Using
      convenience sampling methods, 361 street-based FSWs were recruited from August
      2011 to February 2012. All participants completed an anonymous questionnaire on
      socioeconomic and sex behavioral information and were tested for HIV and
      syphilis. Risk for HIV and syphilis infection was assessed using univariate and
      multivariate logistic regression analyses. RESULTS: No HIV infections were found.
      The prevalence rate of syphilis was 43.5%. Nearly 46.1% of street-based FSWs
      reported having education for no more than 6 years. Having reproductive tract
      infections at current visit, duration of sex work more than 5 years, indulgence
      in unprotected sex trade in the last time, unprotected sex trade in the last
      month, and unprotected sex with boyfriend or spouse in the last month were
      reported by 35.2%, 43.5%, 33.8%, 60.4%, and 93.1% street-based FSWs,
      respectively. In multivariate logistic regression analysis, having reproductive
      tract infections at current visit [odds ratio (OR), 12.10; 95% confidence
      interval (CI), 6.01-24.37], duration of sex work more than five years (OR, 4.26;
      95% CI, 2.40-7.54), and unprotected sex trade in the last month (OR, 1.85; 95%
      CI, 1.06-3.22) were independently associated with syphilis infection. CONCLUSION:
      The prevalence rate of syphilis among street-based FSWs is very high. Most street
      based FSWs in our survey had low education, long experience of commercial sex,
      and high rate of inconsistent condom use. Comprehensive interventions targeting
      this high-risk group, especially scaling up screening and ensuring consistent use
      of condoms during sex are needed.

PMID- 25396128
TI  - Increased prevalence of thyroid dysfunction and diabetes mellitus in Indian
      vitiligo patients: A case-control study.
AB  - BACKGROUND: Though it is well-known that vitiligo is associated with other
      autoimmune disorders, few Indian studies have focused on the relation between
      vitiligo, autoimmune thyroid dysfunction and diabetes mellitus. MATERIALS AND
      METHODS: This case-control study included 150 new cases of vitiligo and 100 age
      and sex-matched controls. A complete history and thorough dermatological
      examination was done. Serum samples from both patients and controls were
      collected and assayed for triiodothyronine, thyroxine, thyroid-stimulating
      hormone, anti-thyroid antibodies-anti-thyroid peroxidase and anti-thyroglobulin
      and fasting plasma glucose. RESULTS: Thyroid hormonal profile revealed autoimmune
      thyroid dysfunction manifesting as hypothyroidism in 30 (20%) vitiligo patients
      and two controls (2%). Diabetes mellitus was present in 24 (16%) vitiligo
      patients and five controls. Seven (4.7%) patients had both hypothyroidism and
      diabetes mellitus. CONCLUSION: There is a clear association between vitiligo,
      autoimmune hypothyroidism and diabetes mellitus. It would be very useful to
      screen for thyroid dysfunction and diabetes mellitus in all patients with
      vitiligo.

PMID- 25396129
TI  - A clinico-histopathological study of lupus vulgaris: A 3 year experience at a
      tertiary care centre.
AB  - BACKGROUND: Lupus vulgaris is the most common form of cutaneous tuberculosis in
      adults. Lupus vulgaris is caused by hematogenous, lymphatic, or contiguous spread
      from elsewhere in the body. histologically it is charecterised by typical
      tubercles with or without caseation, surrounded by epitheloid histiocytes and
      multinucleate giant cells in the superficial epidermis with prominent peripheral
      lymphocytes. MATERIALS AND METHOD: All cases of clinically and histopathologicaly
      diagnosed lupus vulgaris over the previous five years were included in the study.
      RESULTS: Fourteen cases of lupus vulgaris cases reported during the study period
      with eaqual incidence among males and females. DISCUSSION: Plaque type of lupus
      vulgaris was the most common type. Histopathologically tubercular granulomas were
      seen in all cases as compared to other studies. CONCLUSION: Different patterns of
      lupus vulgaris are reported.

PMID- 25396130
TI  - Scleredema adultorum of Buschke over an unusual site associated with pregnancy.
AB  - Scleredema adultorum of Buschke is characterized by symmetrical, diffuse, non
      pitting erythematous swelling of the skin due to accumulation of collagen and
      mucopolysaccharides in the dermis. Herein we report a case of scleredema over an
      unusual site in a pregnant woman. 

PMID- 25396131
TI  - Pedunculated poroma on forearm: A rare clinical presentation.
AB  - Eccrine poroma (EP) is an adnexal tumor that commonly occurs on soles as a soft
      sessile flesh colored nodule. We report here a case of 54-year-old man who
      presented with a pedunculated red colored nodule on the right forearm.
      Histopathological examination was consistent with EP. This presentation of EP on
      the forearm as a pedunculated nodule is rare. 

PMID- 25396132
TI  - Angiokeratoma circumscriptum neviforme: An entity, few and far between.
AB  - Angiokeratomas are a group of vascular ectasias that involve the papillary dermis
      and may produce papillomatosis, acanthosis and hyperkeratosis of the epidermis.
      Angiokeratoma circumscriptum is the least common variant among many types.
      Angiokeratoma circumscriptum neviforme is a still rarer variety of angiokeratoma,
      which is classically seen at birth. We report here a case of congenital, linear,
      unilateral, verrucous plaques on the leg of a young girl, diagnosed as
      angiokeratoma circumscriptum neviforme (ACN). 

PMID- 25396133
TI  - Congenital atrichia associated with nevus flammeus: A rare association.
AB  - Congenital atrichia is the absence of hair over the entire body at birth, an
      inherited condition that may be isolated or associated with other anomalies.
      Herein we report a case of isolated congenital atrichia with nevus flammeus. 

PMID- 25396134
TI  - Hutchinson - Gilford progeria syndrome: A rare case report.
AB  - Hutchinson - Gilford Progeria Syndrome is a rare genetic disorder characterized
      by premature aging involving the skin, bones, heart, and blood vessels. We report
      a three-year-old boy with clinical manifestations characteristic of this
      syndrome. He had a characteristic "plucked-bird" appearance, prominent eyes and
      scalp veins, senile look, loss of scalp hair, eyebrows, and eyelashes, stunted
      growth, and mottled pigmentation with sclerodermatous changes over the trunk and
      lower limbs. Radiological changes and decreased high-density lipoprotein (HDL)
      levels were also characteristic of the syndrome. This interesting case is
      reported for its rarity. 

PMID- 25396135
TI  - Dyshidrosiform pemphigoid with Parkinsonism in a nonagenarian Maharashtrian
      female.
AB  - Dyshidrosiform pemphigoid is a rare variant of bullous pemphigoid localized to
      the hands and feet whose characteristic subepidermal blisters develop as a result
      of binding of the IgG autoantibodies to intracellular plaque and extracellular
      face of the hemidesmosome recognizing a 230-kDa plakin molecule (BP230, BPAg1or
      BPAg1e) and a 180-kDa transmembrane protein. Neurodegenerative processes (viz.,
      stroke, dementia, Parkinsonism, epilepsy, etc) uncover BPAg1-n, an alternatively
      spliced form of BPAg1-e that stabilizes the cytoskeleton of sensory neurons,
      generating autoantibodies that may subsequently lead to BP by cross-reacting with
      BPAg1-e. We present a patient with Parkinsonism who later developed blisters,
      erosions and crusts localized to the palms and soles, confirmed
      histopathologically as bullous pemphigoid. To the best of our knowledge, ours is
      the first case report from India wherein Parkinsonism-generated autoantibodies
      led to the development of dyshidrosiform pemphigoid due to their cross-reactivity
      with BPAg1-e. 

PMID- 25396136
TI  - Coexistence of mucous membrane pemphigoid and vitiligo.
AB  - Mucous membrane pemphigoid describes a rare heterogeneous group of chronic,
      inflammatory, mucous membrane-dominated, subepithelial blistering diseases that
      manifest a varying constellation of oral, ocular, skin, genital, nasopharyngeal,
      esophageal, and laryngeal lesions. Life-threatening airway obstruction and sight
      threatening ocular scarring can occur in this condition, which is rarely reported
      in Indian literature. Vitiligo is another acquired autoimmune disorder
      characterized by loss of melanocytes. Vitiligo is associated with a number of
      disorders also considered to be autoimmune. Here we report a very rare
      coexistence of MMP and vitiligo, the first such report from India. 

PMID- 25396137
TI  - Clear cell sarcoma.
AB  - Malignant melanoma (MM) of soft tissue, also called clear cell sarcoma (CCS) of
      tendons and aponeuroses, derives from the neural crest. CCS is similar
      morphologically to MM but has no precursor skin lesion, and instead, has a
      characteristic chromosomal translocation. Prognosis is related to the tumor size.
      Early recognition and initial radical surgery is the key to a favorable outcome.
      The tumor has to be differentiated from other benign and malignant lesions of the
      soft tissues, such as fibrosarcoma. The demonstration of melanin and a positive
      immunohistochemical reaction for S-100 protein and HMB-45 can assist in the
      differential diagnosis. We report the case of a 58-year-old woman with CCS
      arising from the soft tissue of her little finger. 

PMID- 25396138
TI  - Follicular occlusion tetrad.
AB  - Follicular occlusion tetrad is a symptom complex consisting of four conditions
      having a similar pathophysiology. It includes Hidradenitis suppurativa, acne
      conglobata, dissecting cellulitis of the scalp and pilonidal sinus. The exact
      pathogenesis of this group of disease is unknown but evidence suggests that they
      share the same pathological process initiated by follicular occlusion in apocrine
      gland bearing areas. Though each of these conditions is commonly encountered
      singly, follicular occlusion tetrad as a symptom complex has been rarely reported
      in the literature. 

PMID- 25396139
TI  - Kerion mimicking bacterial infection in an elderly patient.
AB  - Tinea capitis is generally thought to be a common disease in children but not in
      adults. When infection does occur in adults, it may have an atypical appearance.
      We report an elderly female with inflammatory tinea capitis caused by
      Trichophyton rubrum. She had numerous pustular lesions throughout the scalp with
      alopecia, initially treated for bacterial infection. We concluded that tinea
      capitis should remain in the differential diagnosis of elderly patients with
      alopecia and pyoderma like presentations and culture test should be routinely
      done in such patients to avoid complications. 

PMID- 25396140
TI  - Bullous mastocytosis in a 3-month-old infant.
AB  - Mastocytosis is a rare myeloid neoplasm characterized by abnormal proliferation
      and accumulation of mast cells in one or more organ systems including the skin,
      bone marrow, liver, spleen, lymph nodes and gastrointestinal tract. An infant
      presenting with bullous lesions is an even rarer clinical presentation of
      cutaneous mastocytosis. The symptoms and complications are mostly in proportion
      to the mast cell degranulation in tissues. Management is focused on preventing
      and treating this event. We report a three-month-old infant with bullous
      mastocytosis to enhance awareness about this rare diagnosis. 

PMID- 25396141
TI  - Lichen striatus associated with psoriasis vulgaris treated with oral acitretin.
AB  - Lichen striatus (LS) is an uncommon dermatosis of unknown etiology that presents
      as a continuous or interrupted linear band of pink, tan, red or skin-colored
      papules in a blaschkoid distribution. The lesions are generally solitary and
      unilateral, but unusual extensive cases with multiple and bilateral lesions have
      been also described. Albeit LS is typically an asymptomatic and self-limited
      dermatosis, it may cause a significant psychological distress in some patients,
      thus requiring an appropriate therapy. Topical steroid is the most commonly used
      treatment but it is not always effective. We report a case of LS unresponsive to
      topical steroid therapy associated with psoriasis vulgaris successfully treated
      with oral acitretin. 

PMID- 25396142
TI  - Epidermotropism of lepra bacilli in a patient with histoid Hansen's disease.
AB  - Histoid leprosy is a rare form of multibacillary leprosy with distinct clinical
      and histopathological features. It is a variant of lepromatous leprosy with a
      very high bacillary load. It appears in patients as relapse after dapsone
      monotherapy and resistance or rarely, "de novo." Although leprosy is slowly
      declining the exact mode of transmission is unclear. At least until recently, the
      most widely held belief was that the disease was transmitted by contact between
      cases of leprosy and healthy persons. Transmission by the respiratory route is
      also gaining ground. There are other possibilities such as transmission through
      insects, which cannot be completely ruled out. However, the present case report
      possibly suggests the role of skin as a portal of both exit and entry for the
      bacillus in histoid leprosy transmission. De novo form of histoid leprosy has
      numerous solid staining bacteria inside the epidermis. The reports show that
      these bacilli can be eliminated from the intact epidermis, which indicate an
      unusual role of the skin in the transmission of leprosy. 

PMID- 25396143
TI  - Initial presentation of acute myelogenous leukemia in the infiltrate underlying
      an actinic keratosis.
AB  - We report an 85-year-old female patient who presented with an erythematous
      keratotic lesion on her temple suspicious of squamous cell carcinoma.
      Histological evaluation revealed actinic keratosis, but the underlying atypical
      infiltrate contained atypical myeloid forms consistent with acute myelogenous
      leukemia (AML). Upon further questioning, it was determined that the patient had
      a history of myelodysplastic syndrome. Her skin biopsy provided the first
      evidence of progression to AML. This case serves as an important reminder of the
      role the dermatopathologist plays in identifying serious systemic disease. 

PMID- 25396145
TI  - Lesser known evil of a commonly used devil-bleomycin induced flagellate
      dermatitis.

PMID- 25396144
TI  - Pentoxifylline and its applications in dermatology.
AB  - Pentoxifylline is a methyl-xanthine derivative with many anti inflammatory
      effects. Pentoxifylline has been found to be effective for many dermatological as
      well as non-dermatological conditions. It has been used both as primary drug as
      well as adjuvant and is a safe and relatively cost-effective alternative drug. In
      this article, we review the literature and highlight various important aspects of
      pentoxifylline. 

PMID- 25396146
TI  - Rothmund-Thomson syndrome.

PMID- 25396147
TI  - Extensive nevus comedonicus.

PMID- 25396148
TI  - Mal de Meleda: A report of two siblings in one family.

PMID- 25396149
TI  - Hidradenoma papilliferum of the vulva.

PMID- 25396150
TI  - Pellgra revisited.

PMID- 25396151
TI  - Bowen's disease: An unusual clinical presentation.

PMID- 25396152
TI  - Unilateral pityriasis rosea.

PMID- 25396153
TI  - Yellow nail syndrome: A rare entity.

PMID- 25396154
TI  - Pathophysiology, clinical assessment, and investigations involving leg ulcers.

PMID- 25396155
TI  - Compression therapy for leg ulcers.

PMID- 25396156
TI  - Preventing leg ulcer recurrence.

PMID- 25396157
TI  - Leg ulcers: An Indian perspective.

PMID- 25396158
TI  - Quality-of-life with leg ulcers.

PMID- 25396159
TI  - Adjunctive treatment for leg ulcers.

PMID- 25396160
TI  - Systemic therapy for leg ulcers.

PMID- 25396161
TI  - Guidelines for managing the leg ulcer.

PMID- 25396162
TI  - Leg ulcers: Recommendations.

PMID- 25396163
TI  - SkIndia Quiz 15: Hyperpigmented and purpuric plaques on trunk.

PMID- 25396165
TI  - Loose anagen hair syndrome.

PMID- 25396164
TI  - Bowen's disease: A favorable response to imiquimod.

PMID- 25396166
TI  - Milia en plaque.

PMID- 25396167
TI  - Pup tent sign.

PMID- 25396168
TI  - Hair casts.
AB  - Hair casts or pseudonits are circumferential concretions, which cover the hair
      shaft in such a way that, it could be easily removed. They are thin, cylindrical,
      and elongated in length. We present an unusual case of an 8-year-old girl
      presenting with hair casts. Occurrence of these is unusual, and they may have
      varied associations. This patient was suffering from developmental delay. It is
      commonly misdiagnosed as and very important to differentiate from pediculosis
      capitis. 

PMID- 25396169
TI  - De novo histoid leprosy.

PMID- 25396170
TI  - Targetoid hemosiderotic hemangioma.

PMID- 25396171
TI  - How journal metrics illustrate the transformation of archives of plastic surgery
      into an international journal.

PMID- 25396173
TI  - Multifactorial approaches for correction of the drooping tip of a long nose in
      East asians.
AB  - A long nose with a drooping tip is a major aesthetic problem. It creates a
      negative and aged appearance and looks worse when smiling. In order to rectify
      this problem, the underlying anatomical causes should be understood and corrected
      simultaneously to optimize surgical outcomes. The causes of a drooping tip of a
      long nose are generally classified into two mechanisms. Static causes usually
      result from malposition and incorrect innate shape of the nasal structure: the
      nasal septum, upper and lower lateral cartilages, and the ligaments in between.
      The dynamic causes result from the facial expression muscles, the depressor septi
      nasi muscle, and the levator labii superioris alaeque nasi muscle. The depressor
      septi nasi depresses the nasal tip and the levator labii superioris alaeque nasi
      pulls the alar base upwards. Many surgical methods have been introduced, but
      partial approaches to correct such deformities generally do not satisfy East
      Asians, making the problem more challenging to surgeons. Typically, East Asians
      have thick nasal tip soft tissue and skin, and a depressed columella and alar
      bases. The authors suggest that multifactorial approaches to static and dynamic
      factors along with ancillary causes should be considered for correcting the
      drooping tip of the long noses of East Asians. 

PMID- 25396172
TI  - Recent developments in the use of intralesional injections keloid treatment.
AB  - Keloid scars are often considered aesthetically unattractive and frustrating
      problems that occur following injuries. They cause functional and cosmetic
      deformities, displeasure, itching, pain, and psychological stress and possibly
      affect joint movement. The combination of these factors ultimately results in a
      compromised quality of life and diminished functional performance. Various
      methods have been implemented to improve keloid scars using both surgical and non
      surgical approaches. However, it has proven to be a challenge to identify a
      universal treatment that can deliver optimal results for all types of scars.
      Through a PubMed search, we explored most of the literature that is available
      about the intralesional injection treatment of hypertrophic scars and keloids and
      highlights both current (corticosteroid, 5-fluorouracil, bleomycin, interferon,
      cryotherapy and verapamil) and future treatments (interleukin-10 and botulinum
      toxin type A). The reference lists of retrieved articles were also analysed.
      Information was gathered about the mechanism of each injection treatment, its
      benefits and associated adverse reactions, and possible strategies to address
      adverse reactions to provide reliable guidelines for determining the optimal
      treatment for particular types of keloid scars. This article will benefit
      practitioners by outlining evidence-based treatment strategies using
      intralesional injections for patients with hypertrophic scars and keloids. 

PMID- 25396174
TI  - Bio-conjugated polycaprolactone membranes: a novel wound dressing.
AB  - BACKGROUND: The combination of polycaprolactone and hyaluronic acid creates an
      ideal environment for wound healing. Hyaluronic acid maintains a moist wound
      environment and accelerates the in-growth of granulation tissue. Polycaprolactone
      has excellent mechanical strength, limits inflammation and is biocompatible. This
      study evaluates the safety and efficacy of bio-conjugated polycaprolactone
      membranes (BPM) as a wound dressing. METHODS: 16 New Zealand white rabbits were
      sedated and local anaesthesia was administered. Two 3.0*3.0 cm full-thickness
      wounds were created on the dorsum of each rabbit, between the lowest rib and the
      pelvic bone. The wounds were dressed with either BPM (n=12) or Mepitel (n=12)
      (control), a polyamide-silicon wound dressing. These were evaluated
      macroscopically on the 7th, 14th, 21st, and 28th postoperative days for
      granulation, re-epithelialization, infection, and wound size, and histologically
      for epidermal and dermal regeneration. RESULTS: Both groups showed a comparable
      extent of granulation and re-epithelialization. No signs of infection were
      observed. There was no significant difference (P>0.05) in wound size between the
      two groups. BPM (n=6): 8.33 cm(2), 4.90 cm(2), 3.12 cm(2), 1.84 cm(2); Mepitel
      (n=6): 10.29 cm(2), 5.53 cm(2), 3.63 cm(2), 2.02 cm(2); at the 7th, 14th, 21st,
      and 28th postoperative days. The extents of epidermal and dermal regeneration
      were comparable between the two groups. CONCLUSIONS: BPM is comparable to Mepitel
      as a safe and efficacious wound dressing.

PMID- 25396175
TI  - The effect of platelet-rich plasma on survival of the composite graft and the
      proper time of injection in a rabbit ear composite graft model.
AB  - BACKGROUND: Administration of growth factors has been associated with increased
      viability of composite grafts greater than 1-cm in diameter. Platelet-rich plasma
      (PRP) contains many of the growth factors studied. In this study, we evaluate the
      effect of PRP injection on composite graft viability and the proper time for
      injection. METHODS: A total of 24 New Zealand White rabbits were divided into
      four groups. Autologous PRP was injected into the recipient sites three days
      before grafting in group 1, on the day of grafting in group 2, and three days
      after grafting in group 3. Group 4 served as control without PRP administration.
      Auricular composite grafts of 3-cm diameter were harvested and grafted back into
      place after being rotated 180 degrees. Median graft viability and microvessel
      density were evaluated at day 21 of graft via macroscopic photographs and
      immunofluorescent staining, respectively. RESULTS: The median graft survival rate
      was 97.8% in group 1, 69.2% in group 2, 55.7% in group 3, and 40.8% in the
      control group. The median vessel counts were 34 (per *200 HPF) in group 1, 24.5
      in group 2, 19.5 in group 3, and 10.5 in the control group. CONCLUSIONS: This
      study demonstrates that PRP administration is associated with increased composite
      graft viability. All experimental groups showed a significantly higher survival
      rate and microvessel density, compared with the control group. Pre-administration
      of PRP was followed by the highest graft survival rate and revascularization. PRP
      treatments are minimally invasive, fast, easily applicable, and inexpensive, and
      offer a potential clinical pathway to larger composite grafts.

PMID- 25396176
TI  - Expression of nuclear factor erythroid 2 protein in malignant cutaneous tumors.
AB  - BACKGROUND: Reactive oxygen species (ROS) damages cell molecules, and modifies
      cell signaling. The nuclear factor E2-related factor (Nrf2) is a critical
      transcription regulator, which protects cells against oxidative damage. Nrf2
      expression is increased in a large number of cancers. However, little information
      has been reported regarding the expression of Nrf2 in skin cancers. Hence, we
      explored the expression of Nrf2 protein in skin cancers. METHODS: The Nrf2
      protein expression in 24 specimens, including 6 malignant melanomas (MM), 6
      squamous cell carcinomas (SCC), 6 basal cell carcinomas (BCC), and 6 normal skin
      tissues, was evaluated by western blotting. Immunohistochemical staining was
      performed. The expression of Kelch-like ECH-associated protein 1 (Keap1), the key
      regulator of Nrf2, was also analyzed by western blotting. RESULTS: Small
      interfering RNA transfection to the melanoma cell line G361 confirmed that an
      approximately 66 kDa band was the true Nrf2 band. The western blot revealed that
      the Nrf2 protein was definitely expressed in normal skin tissues, but the Nrf2
      expression was decreased in MM, SCC, and BCC. Immunohistochemical examination
      showed that expression of Nrf2 was decreased in all skin cancer tissues compared
      to the normal skin tissues. Keap1 was not expressed in all malignant skin tumors
      and normal skin tissues by western blot. CONCLUSIONS: ROS was increased in
      various types of cancers which proteins were highly expressed or underexpressed.
      This study demonstrated that the expression of Nrf2 protein was down-regulated in
      human malignant skin tumors. We suggest that decreased expression of Nrf2 is
      related to skin cancers.

PMID- 25396177
TI  - Applicability and safety of in vitro skin expansion using a skin bioreactor: a
      clinical trial.
AB  - BACKGROUND: Tissue expansion is an effective and valuable technique for the
      reconstruction of large skin lesions and scars. This study aimed to evaluate the
      applicability and safety of a newly designed skin expanding bioreactor system for
      maximizing the graft area and minimizing the donor site area. METHODS: A computer
      controlled biaxial skin bioreactor system was used to expand skin in two
      directions while the culture media was changed daily. The aim was to achieve an
      expansion speed that enabled the skin to reach twice its original area in two
      weeks or less. Skin expansion and subsequent grafting were performed for 10
      patients, and each patient was followed for 6 months postoperatively for clinical
      evaluation. Scar evaluation was performed through visual assessment and by using
      photos. RESULTS: The average skin expansion rate was 10.54%+/-6.25%; take rate,
      88.89%+/-11.39%; and contraction rate, 4.2%+/-2.28% after 6 months. Evaluation of
      the donor and recipient sites by medical specialists resulted in an average score
      of 3.5 (out of a potential maximum of 5) at 3 months, and 3.9 at 6 months. The
      average score for patient satisfaction of the donor site was 6.2 (out of a
      potential maximum of 10), and an average score of 5.2 was noted for the recipient
      site. Histological examination performed before and after the skin expansion
      revealed an increase in porosity of the dermal layer. CONCLUSIONS: This study
      confirmed the safety and applicability of the in vitro skin bioreactor, and
      further studies are needed to develop methods for increasing the skin expansion
      rate.

PMID- 25396178
TI  - Influence of negative-pressure wound therapy on tissue oxygenation of the foot.
AB  - BACKGROUND: Negative-pressure wound therapy (NPWT) is believed to accelerate
      wound healing by altering wound microvascular blood flow. Although many studies
      using laser Doppler have found that NPWT increases perfusion, recent work using
      other modalities has demonstrated that perfusion is reduced. The purpose of this
      study was to investigate the influence of NPWT on tissue oxygenation of the foot,
      which is the most sensitive region of the body to ischemia. METHODS:
      Transcutaneous partial pressure of oxygen (TcpO2) was used to determine perfusion
      beneath NPWT dressings of 10 healthy feet. The sensor was placed on the tarso
      metatarsal area of the foot and the NPWT dressing was placed above the sensor.
      TcpO2 was measured until it reached a steady plateau state. The readings obtained
      at the suction-on period were compared with the initial baseline (pre-suction)
      readings. RESULTS: TcpO2 decreased significantly immediately after applying NPWT,
      but gradually increased over time until reaching a steady plateau state. The
      decrease in TcpO2 from baseline to the steady state was 2.9 to 13.9 mm Hg (mean,
      9.3+/-3.6 mm Hg; 13.5+/-5.8%; P<0.01). All feet reached a plateau within 20 to 65
      minutes after suction was applied. CONCLUSIONS: NPWT significantly decrease
      tissue oxygenation of the foot by 2.9 to 13.9 mm Hg. NPWT should be used with
      caution on feet that do not have adequate tissue oxygenation for wound healing.

PMID- 25396179
TI  - Skin thickness of the anterior, anteromedial, and anterolateral thigh: a
      cadaveric study for split-skin graft donor sites.
AB  - BACKGROUND: The depth of graft harvest and the residual dermis available for
      reepithelization primarily influence the healing of split-skin graft donor sites.
      When the thigh region is chosen, the authors hypothesize based on thickness
      measurements that the anterolateral region is the optimal donor site. METHODS:
      Full-thickness skin specimens were sampled from the anteromedial, anterior, and
      anterolateral regions of human cadavers. Skin specimens were cut perpendicularly
      with a custom-made precision apparatus to avoid the overestimation of thickness
      measurements. The combined epidermal and dermal thicknesses (overall skin
      thickness) were measured using a digital calliper. The specimens were
      histologically stained to visualize their basement membrane, and microscopy
      images were captured. Since the epidermal thickness varies across the specimen, a
      stereological method was used to eliminate observer bias. RESULTS: Epidermal
      thickness represented 2.5% to 9.9% of the overall skin thickness. There was a
      significant difference in epidermal thickness from one region to another
      (P<0.05). The anterolateral thigh region had the most consistent and highest mean
      epidermal thickness (60+/-3.2 um). We observed that overall skin thickness
      increased laterally from the anteromedial region to the anterior and
      anterolateral regions of the thigh. The overall skin thickness measured 1,032+/
      435 um in the anteromedial region compared to 1,220+/-257 um in the anterolateral
      region. CONCLUSIONS: Based on skin thickness measurements, the anterolateral
      thigh had the thickest epidermal and dermal layers. We suggest that the
      anterolateral thigh region is the optimal donor site for split-skin graft
      harvests from the thigh.

PMID- 25396180
TI  - Subbrow approach as a minimally invasive reduction technique in the management of
      frontal sinus fractures.
AB  - BACKGROUND: Frontal sinus fractures, particularly anterior sinus fractures, are
      relatively common facial fractures. Many agree on the general principles of
      frontal fracture management; however, the optimal methods of reduction are still
      controversial. In this article, we suggest a simple reduction method using a
      subbrow incision as a treatment for isolated anterior sinus fractures. METHODS:
      Between March 2011 and March 2014, 13 patients with isolated frontal sinus
      fractures were treated by open reduction and internal fixation through a subbrow
      incision. The subbrow incision line was designed to be precisely at the lower
      margin of the brow in order to obtain an inconspicuous scar. A periosteal
      incision was made at 3 mm above the superior orbital rim. The fracture site of
      the frontal bone was reduced, and bone fixation was performed using an absorbable
      plate and screws. RESULTS: Contour deformities were completely restored in all
      patients, and all patients were satisfied with the results. Scars were barely
      visible in the long-term follow-up. No complications related to the procedure,
      such as infection, uncontrolled sinus bleeding, hematoma, paresthesia, mucocele,
      or posterior wall and brain injury were observed. CONCLUSIONS: The subbrow
      approach allowed for an accurate reduction and internal fixation of the fractures
      in the anterior table of the frontal sinus by providing a direct visualization of
      the fracture. Considering the surgical success of the reduction and the rigid
      fixation, patient satisfaction, and aesthetic problems, this transcutaneous
      approach through a subbrow incision is concluded to be superior to the other
      reduction techniques used in the case of an anterior table frontal sinus
      fracture.

PMID- 25396181
TI  - Orbital wall restoring surgery in pure blowout fractures.
AB  - BACKGROUND: Restoring orbital volume in large blowout fractures is still a
      technically challenge to the orbital surgeon. In this study, we restored the
      orbital wall using the combination of transorbital and transnasal approach with
      additional supports from the paranasal sinuses, and we compared the surgical
      outcome to that of a conventional transorbital method. METHODS: A retrospective
      review of all patients with pure unilateral blowout fractures between March 2007
      and March 2013 was conducted. 150 patients were classified into two groups
      according to the surgical method: conventional transorbital method (group A, 75
      patients, control group), and the combination of transorbital and transnasal
      approach with additional supports from the paranasal sinuses (group B, 75
      patients, experimental group). Each group was subdivided depending on fracture
      location: group I (inferior wall), group IM (inferomedial wall), and group M
      (medial wall). The surgical results were assessed by the Hertel scale and a
      comparison of preoperative and postoperative orbital volume ratio (OVR) values.
      RESULTS: In the volumetric analysis, the OVR decreased more by the experimental
      groups than each corresponding control groups (P<0.05). Upon ophthalmic
      examination, neither the differences among the groups in the perioperative Hertel
      scale nor the preoperative and postoperative Hertel scales were statistically
      significant (P>0.05). CONCLUSIONS: Our surgical results suggest that orbital
      volume was more effectively restored by the combination of transorbital and
      transnasal approach with additional supports from the paranasal sinuses than the
      conventional method, regardless of the type of fracture.

PMID- 25396182
TI  - Practical considerations for perforator flap thinning procedures revisited.
AB  - BACKGROUND: A thin perforator flap is one of the best methods for covering
      defects. This study aimed to revisit and further test the rapidly advancing field
      of flap thinning techniques. METHODS: We performed two cadaveric studies to test
      the known flap thinning methods, and then applied these methods to a clinical
      series. In the first study, five cadavers were used to observe the anatomical
      relation of the perforator with the subdermal plexuses and the subcutaneous fat
      layer by injecting a colored latex solution. The second study was done on four
      cadavers independently from the first study. Last, a clinical series was
      performed on 15 patients. RESULTS: The areolar fat lobules of 10 anterolateral
      thigh perforator (ALT), seven deep inferior epigastric artery perforator (DIEAP),
      and six thoracodorsal artery perforator (TAP) flaps were dissected to reduce the
      flap thickness guided by the colored vascular pattern. On average, the ALT,
      DIEAP, and TAP flaps were reduced to 32.76%+/-9.76%, 37.01%+/-9.21%, and 35.42%+/
      9.41%, respectively. In the second study, the areolar fat lobules were directly
      dissected in six ALT, six TAP, and four MSAP flaps, and an average reduction in
      flap thickness of 53.41%+/-5.64%, 52.30%+/-2.88%, and 47.87%+/-6.41%,
      respectively, was found. In the clinical series, 13 out of the 15 cases yielded
      satisfactory outcomes with an average thickness reduction of 37.91%+/-7.15%.
      CONCLUSIONS: These multiple studies showed that the deep fat layer could be
      safely removed to obtain a thin yet viable perforator flap. This evidence
      suggests that the macroscopic flap thinning technique can achieve thin flaps.
      Surgeons should consider this technique before embracing the latest technique of
      supermicrosurgery.

PMID- 25396183
TI  - The superficial inferior epigastric artery flap and its relevant vascular anatomy
      in korean women.
AB  - BACKGROUND: Lower abdominal soft tissue transfer is the standard procedure for
      breast reconstruction. However, abdominal wall weakness and herniation commonly
      occur postoperatively at the donor site. To reduce the morbidities of the donor
      site, the superficial inferior epigastric artery (SIEA) flap was introduced, but
      inconsistent anatomy of the SIEA has reduced its utility. In the present study,
      the anatomy of the superficial inferior epigastric vessels in Korean women was
      determined with regards to breast reconstructive surgery. METHODS: The vascular
      anatomies of the SIEA and superficial inferior epigastric vein (SIEV) were
      evaluated on 32 breast cancer patients receiving free transverse rectus abdominis
      musculocutaneous flap reconstruction after mastectomy. The existence, pulsation,
      location, external diameter, and depth of the SIEA and SIEV were measured at the
      lower abdominal incision level. RESULTS: SIEA and SIEV were present in 48/64
      (75.00%) and 63/64 (98.44%) hemi-abdomens, respectively. Pulsation of the SIEA
      was found in 44/48 (91.67%) cases. The mean locations of SIEA and SIEV were +5.79
      (+/-12.87) mm, and -8.14 (+/-15.24) mm from the midpoint between the anterior
      superior iliac spine and symphysis pubis, respectively. The mean external
      diameters of SIEA and SIEV were 1.20 (+/-0.39) mm and 1.37 (+/-0.33) mm, and they
      were found at a mean depth of 9.75 (+/-2.67) mm and 8.33 (+/-2.65) mm,
      respectively. CONCLUSIONS: The SIEA was absent in 25% of Korean women and had a
      relatively small caliber. Therefore, careful preoperative assessment of the lower
      abdominal vasculature is required to achieve successful breast reconstruction
      using SIEA flaps.

PMID- 25396184
TI  - Distally Based Sural Artery Adipofascial Flap based on a Single Sural Nerve
      Branch: Anatomy and Clinical Applications.
AB  - BACKGROUND: The distally based sural artery flap is a reliable, local
      reconstructive option for small soft tissue defects of the distal third of the
      leg. The purpose of this study is to describe an adipofascial flap based on a
      single sural nerve branch without sacrificing the entire sural nerve, thereby
      preserving sensibility of the lateral foot. METHODS: The posterior aspect of the
      lower limb was dissected in 15 cadaveric limbs. Four patients with soft tissue
      defects over the tendo-achilles and ankle underwent reconstruction using the
      adipofascial flap, which incorporated the distal peroneal perforator, short
      saphenous vein, and a single branch of the sural nerve. RESULTS: From the
      anatomical study, the distal peroneal perforator was situated at an average of
      6.2 cm (2.5-12 cm) from the distal tip of the lateral malleolus. The medial and
      lateral sural nerve branches ran subfascially and pierced the muscle fascia 16 cm
      (14-19 cm) proximal to the lateral malleolus to enter the subcutaneous plane.
      They merged 1-2 cm distal to the subcutaneous entry point to form the common
      sural nerve at a mean distance of 14.5 cm (11.5-18 cm) proximal to the lateral
      malleolus. This merging point determined the pivot point of the flap. In the
      clinical cases, all patients reported near complete recovery of sensation over
      the lateral foot six months after surgery. All donor sites healed well with a
      full range of motion over the foot and ankle. CONCLUSIONS: The distally based
      sural artery adipofascial flap allowed for minimal sensory loss, a good range of
      motion, an aesthetically acceptable outcome and can be performed by a single
      surgeon in under 2 hours.

PMID- 25396185
TI  - An algorithm to guide recipient vessel selection in cases of free functional
      muscle transfer for facial reanimation.
AB  - BACKGROUND: The aim of this study was to review the recipient vessels used in our
      cases of facial reanimation with free functional muscle transfer and to identify
      patient variables that may predict when the facial vessels are absent. From this
      we present a protocol for vessel selection in cases when the facial artery and/or
      vein are absent. METHODS: Patients were identified from November 2006 to October
      2013. Data was collected on patient demographics, facial palsy aetiology, history
      of previous facial surgery/trauma and flap/recipient vessels used. A standard
      operative approach was adopted and performed by a single surgeon. RESULTS: Eighty
      seven eligible patients were identified for inclusion amongst which 98 hemifaces
      were operated upon. The facial artery and vein were the most commonly used
      recipient vessels (90% and 83% of patients, respectively). Commonly used
      alternative vessels were the transverse facial vein and superficial temporal
      artery. Those with congenital facial palsy were significantly more likely to lack
      a suitable facial vein (P=0.03) and those with a history of previous facial
      surgery or trauma were significantly more likely to have an absent facial artery
      and vein (P<0.05). CONCLUSIONS: Our algorithm can help to guide vessel selection
      cases of facial reanimation with free functional muscle transfer. Amongst
      patients with congenital facial palsy or in those with a previous history of
      facial surgery or trauma, the facial vessels are more likely to be absent and so
      the surgeon should then look towards the transverse facial vein and superficial
      temporal artery as alternative recipient structures.

PMID- 25396186
TI  - Comparison of the complications in vertical rectus abdominis musculocutaneous
      flap with non-reconstructed cases after pelvic exenteration.
AB  - BACKGROUND: Perineal reconstruction following pelvic exenteration is a
      challenging area in plastic surgery. Its advantages include preventing
      complications by obliterating the pelvic dead space and minimizing the scar by
      using the previous abdominal incision and a vertical rectus abdominis
      musculocutaneous (VRAM) flap. However, only a few studies have compared the
      complications and the outcomes following pelvic exenteration between cases with
      and without a VRAM flap. In this study, we aimed to compare the complications and
      the outcomes following pelvic exenteration with or without VRAM flap coverage.
      METHODS: We retrospectively reviewed the cases of nine patients for whom
      transpelvic VRAM flaps were created following pelvic exenteration due to pelvic
      malignancy. The complications and outcomes in these patients were compared with
      those of another nine patients who did not undergo such reconstruction. RESULTS:
      Flap reconstruction was successful in eight cases, with minor complications such
      as wound infection and dehiscence. In all cases in the reconstructed group (n=9),
      structural integrity was maintained and major complications including bowel
      obstruction and infection were prevented by obliterating the pelvic dead space.
      In contrast, in the control group (n=9), peritonitis and bowel obstruction
      occurred in 1 case (11%). CONCLUSIONS: Despite the possibility of flap failure
      and minor complications, a VRAM flap can result in adequate perineal
      reconstruction to prevent major complications of pelvic exenteration.

PMID- 25396187
TI  - Periareolar augmentation mastopexy with interlocking gore-tex suture,
      retrospective review of 50 consecutive patients.
AB  - BACKGROUND: Periareolar Augmentation Mastopexy is one of the most challenging
      operations in plastic surgery. Problems with scar quality, areolar widening, and
      distortion are frequent problems that interfere with a predictable result.
      METHODS: A retrospective review was performed on fifty consecutive patients who
      underwent a periareolar augmentation mastopexy with the interlocking approach. Of
      the 50 patients, 30 had both preoperative and postoperative photographs and were
      the basis of the study. RESULTS: The age of the patients ranged from 19 to 56
      years with the average age being 39 years. The postoperative follow-up averaged
      9.5 months and the implants averaged 316 mL. There were no deaths, pulmonary
      embolism, deep vein thrombosis, or infected implants. Four patients had
      complications following surgery for an overall complication rate of 13%. Two
      patients developed an infected Gore-Tex suture. Two of these complications were
      treated with revision surgery. Five patients required reoperation for an overall
      reoperative rate of 16% (one patient was converted to a full mastopexy).
      CONCLUSIONS: As a result of this retrospective study, we have found the
      interlocking approach to periareolar augmentation/mastopexy to be a safe and
      reliable operation.

PMID- 25396188
TI  - A retrospective analysis of ruptured breast implants.
AB  - BACKGROUND: Rupture is an important complication of breast implants. Before
      cohesive gel silicone implants, rupture rates of both saline and silicone breast
      implants were over 10%. Through an analysis of ruptured implants, we can
      determine the various factors related to ruptured implants. METHODS: We performed
      a retrospective review of 72 implants that were removed for implant rupture
      between 2005 and 2014 at a single institution. The following data were collected:
      type of implants (saline or silicone), duration of implantation, type of implant
      shell, degree of capsular contracture, associated symptoms, cause of rupture,
      diagnostic tools, and management. RESULTS: Forty-five Saline implants and 27
      silicone implants were used. Rupture was diagnosed at a mean of 5.6 and 12 years
      after insertion of saline and silicone implants, respectively. There was no
      association between shell type and risk of rupture. Spontaneous was the most
      common reason for the rupture. Rupture management was implant change (39 case),
      microfat graft (2 case), removal only (14 case), and follow-up loss (17 case).
      CONCLUSIONS: Saline implants have a shorter average duration of rupture, but
      diagnosis is easier and safer, leading to fewer complications. Previous
      generation silicone implants required frequent follow-up observation, and it is
      recommended that they be changed to a cohesive gel implant before hidden rupture
      occurs.

PMID- 25396189
TI  - Autologous Fat Graft in the Reconstructed Breast: Fat Absorption Rate and Safety
      based on Sonographic Identification.
AB  - BACKGROUND: Autologous fat graft has become a useful technique for correction of
      acquired contour deformity in reconstructed breasts. However, there remains
      controversial regarding the efficacy and safety of the practice for
      reconstructive breast surgery. METHODS: A retrospective review was performed on
      102 patients who had secondary fat grafting after breast reconstruction. Fat
      harvest, refinement and injection were done by Coleman's technique. All patients
      were followed up postoperatively within 1 month and after 6 months including
      physical examination and ultrasonography. In 38 patients, the reabsorption rate
      was calculated by serial changes of thickness between skin and pectoral fascia in
      the ultrasonic finding. Locoregional recurrence rate was compared with control
      group of 449 patients who had breast reconstruction without fat graft in the same
      time period. RESULTS: Average 49.3 mL fat was injected into each breast. The most
      common location of fat graft was upper pole, followed by axilla, lower and medial
      breasts. During 28.7 months of average follow-up period, 2.9% of total patients
      had symptoms of palpable mass on fat graft side and ultrasonography identified
      fat necrosis and cyst formation in 17.6% of the patients. Calculated fat
      reabsorption rate was 32.9%. Locoregional recurrence was occurred in 1 patient
      (0.9%) and the rate was not different significantly with control group (2%).
      CONCLUSIONS: Although further studies are required to provide surgeons with
      definitive guidelines for the implementation of fat grafting, we propose
      autologous fat graft is an efficient and safe technique for secondary breast
      reconstruction.

PMID- 25396190
TI  - Gynecomastia surgery is associated with improved nipple location in young korean
      patients.
AB  - BACKGROUND: Gynecomastia is benign enlargement of breast tissue in males and is
      fairly common. Mastectomy not only helps in improving the shape of anterior
      chest, but can also improve the location of nipple. Therefore, a principle
      element of mastectomy design is defining the normal location of nipple based on
      major anatomical reference points. Here, the nipple location was compared for
      before and after gynecomastia surgery. In addition, the same was also compared
      between male patients undergoing gynecomastia surgery and control group of
      subjects without gynecomastia. METHODS: We retrospectively analyzed gynecomastia
      patients who underwent conventional subcutaneous mastectomy. Preoperative and
      postoperative anatomical landmark distances and chest circumferences were
      measured and compared to the same anthropometric data from 20 healthy adult male
      controls. RESULTS: Nipple locations were compared among 13 patients and 20
      controls. The mean weight of resected breast tissue was 246 g, and overall
      patient satisfaction grade was 4.3 out of 5. In the patient group, the slopes for
      the height-distance from the sternal notch to the nipple and chest circumference
      distance between the mid-line of the sternum and the nipple were 0.175 and 0.125
      postoperatively, respectively. The slopes of the control group were 0.122 and
      0.177, respectively; these differences were statistically significant (P<0.05).
      CONCLUSIONS: Nipple positions were considerably lower in patients with
      gynecomastia than in control subjects. Subcutaneous mastectomy was associated
      with mild elevations, but postoperative locations were still lower compared to
      controls. Further efforts are needed to improve the location of postoperative
      nipple-areola complex in patients with gynecomastia.

PMID- 25396191
TI  - The Effectiveness of Mapping Biopsy in Patients with Extramammary Paget's
      Disease.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is an intraepithelial carcinoma
      usually occurring on the skin or mucosa of the perineum. Clinically, it resembles
      eczema or dermatitis, and misdiagnosis and treatment delays are common. The
      treatment of choice for EMPD is a wide excision with adequate margins. Wide
      excision with intraoperative frozen biopsy and Mohs micrographic surgery are
      common methods; however, these are associated with a high recurrence rate and
      long operation time, respectively. METHODS: Between January 2010 and June 2013,
      21 patients diagnosed with EMPD underwent mapping biopsy. Biopsy specimens were
      collected from at least 10 areas, 2 cm from the tumor margin. When the specimens
      were positive for malignancy, additional mapping biopsy was performed around the
      biopsy site of the positive result, and continued until no cancer cells were
      found. Based on the results, excision margins and reconstruction plans were
      established preoperatively. RESULTS: The patients (18 male, 3 female) had a mean
      age of 66.5 years (range, 50-82 years). Almost all cases involved in the perineal
      area, except one case of axillary involvement. Permanent biopsy revealed one case
      (4.8%) of positive cancer cells on the resection margin, in which additional
      mapping biopsy and re-operation was performed. At the latest follow-up (mean,
      27.4 months; range, 12-53 months), recurrence had not occurred. CONCLUSIONS:
      Preoperative mapping biopsy enables accurate resection margins and a preoperative
      reconstructing plan. Additionally, it reduces the operation time and risk of
      recurrence. Accordingly, it represents an effective alternative to Mohs
      micrographic surgery and wide excision with intraoperative frozen biopsy.

PMID- 25396192
TI  - Empirical treatment of highly suspected nontuberculous mycobacteria infections
      following aesthetic procedures.
AB  - BACKGROUND: Infection caused by nontuberculous mycobacteria (NTM) has been
      increasing. Awareness of this infection is crucial yet problematic. Delayed
      management may lead to destructive results. We empirically treated a series of
      patients with clinical suspicion of NTM infection prior to the identification of
      the pathogen. METHODS: A total of 12 patients who developed surgical site
      infections between January 2011 and February 2014 were reviewed. Patients with a
      skin and subcutaneous infection resistant to standard management over two weeks,
      and previous history of aesthetic procedures within three months were regarded as
      highly suspected of having an NTM infection. A variety of diagnostic modalities
      were examined simultaneously, along with starting empirical treatment including a
      combination of clarithromycin and moxifloxacin, and surgical debridement.
      RESULTS: All wounds healed completely within 4 weeks. The mean follow-up duration
      was 7.2 months, and none of the patients developed relapse. Specific NTM
      pathogens were identified in six patients. Eight patients showed caseating
      granuloma implying an NTM infection. One patient showed an uncommon
      Stenotrophomonas infection, which was successfully treated. Three patients had no
      evidence of a pathogen despite repeated microbial tests. Complications such as
      scarring, pigmentation, and disfigurement were common in all the patients.
      CONCLUSIONS: NTM should be considered in the differential diagnosis of an unusual
      skin and soft-tissue infection. We propose an empirical regimen of clarithromycin
      and moxifloxacin as an efficient treatment option for an NTM infection.

PMID- 25396193
TI  - Comparison between Intramedullary Nailing and Percutaneous K-Wire Fixation for
      Fractures in the Distal Third of the Metacarpal Bone.
AB  - BACKGROUND: To compare clinical and radiographic outcomes between intramedullary
      nail fixation and percutaneous K-wire fixation for fractures in the distal third
      portion of the metacarpal bone. METHODS: A single-institutional retrospective
      review identified 41 consecutive cases of metacarpal fractures between September
      2009 and August 2013. Each of the cases met the inclusion criteria for closed,
      extra-articular fractures of the distal third of the metacarpal bone. The
      patients were divided by the method of fixation (intramedullary nailing or K
      wire). Outcomes were compared for mean and median total active motion of the
      digit, radiographic parameters, and period until return to work. Complications
      and symptoms were determined by a questionnaire. RESULTS: During the period under
      review, 41 patients met the inclusion criteria, and the fractures were managed
      with either intramedullary nailing (n=19) or percutaneous K-wire fixation (n=22).
      The mean and median total active range of motion and radiographic healing showed
      no statistically significant difference between the two groups. No union failures
      were observed in either group. The mean operation time was shorter by an average
      of 14 minutes for the percutaneous K-wire fixation group. However, the
      intramedullary nailing group returned to work earlier by an average of 2.3 weeks.
      Complications were reported only in the K-wire fixation group. CONCLUSIONS:
      Intramedullary nailing fixation is advisable for fractures in the distal third of
      the metacarpal bone. It provides early recovery of the range of motion, an
      earlier return to work, and lower complication rates, despite potentially
      requiring a wire removal procedure at the patient's request.

PMID- 25396194
TI  - Rates of readmission after inpatient plastic surgery may not tell the whole
      story.

PMID- 25396195
TI  - Correction of a Misjudgment of Reference in Grabb and Smith's Plastic Surgery
      Seventh Edition.

PMID- 25396196
TI  - Pilomatricoma arising at an influenza vaccination site.

PMID- 25396197
TI  - A ganglion cyst of the temporomandibular joint.

PMID- 25396198
TI  - Extra-abdominal desmoid tumor located in the axilla.

PMID- 25396199
TI  - A giant subpectoral lipoma.

PMID- 25396200
TI  - Retinoblastoma plus lipomatosis: an autosomal dominant syndrome.

PMID- 25396201
TI  - Salvage of a free flap using postoperative percutaneous angioplasty in patients
      with diabetic foot ulcers.

PMID- 25396202
TI  - A new method for forming the pretarsal fullness after lower blepharoplasty.

PMID- 25396203
TI  - Report on attending the asian pacific Federation of societies for reconstructive
      microsurgery 2014.

PMID- 25396204
TI  - Knowledge, moral claims and the exercise of power in global health.
AB  - A number of individuals and organizations have considerable influence over the
      selection of global health priorities and strategies. For some that influence
      derives from control over financial resources. For others it comes from expertise
      and claims to moral authority-what can be termed, respectively, epistemic and
      normative power. In contrast to financial power, we commonly take for granted
      that epistemic and normative forms of power are legitimate. I argue that we
      should not; rather we should investigate the origins of these forms of power, and
      consider under what circumstances they are justly derived. 

PMID- 25396205
TI  - Nurses exposure to workplace violence in a large teaching hospital in Iran.
AB  - BACKGROUND: Workplace violence is one of the factors which can strongly reduce
      job satisfaction and the quality of working life of nurses. The aim of this study
      was to measure nurses' exposure to workplace violence in one of the major
      teaching hospitals in Tehran in 2010. METHODS: We surveyed the nurses in a cross
      sectional design in 2010. The questionnaire was adapted from a standardized
      questionnaire designed collaboratively by the International Labor Office (ILO),
      the International Health Organization (IHO), the International Council of Nurses
      (ICN), and the Public Services International (PSI). Finally, in order to analyze
      the relationships among different variables in the study, T-test and Chi-Square
      test were used. RESULTS: Three hundred and one nurses responded to the
      questionnaire (a response rate of 73%). Over 70% of the nurses felt worried about
      workplace violence. The participants reported exposure to verbal abuse (64% CI:
      59-70%), bullying-mobbing (29% CI: 24-34%) and physical violence (12% CI: 9-16%)
      at least once during the previous year. Relatives of hospital patients were
      responsible for most of the violence. Nurses working in the emergency department
      and outpatient clinics were more likely to report having experienced violence.
      Nurses were unlikely to report violence to hospital managers, and 40% of nurses
      were unaware of any existing policies within the hospital for reducing violence.
      CONCLUSION: We observed a considerable level of nurse exposure to workplace
      violence. The high rate of reported workplace violence demonstrates that the
      existing safeguards that aim to protect the staff from abusive patients and
      relatives are inadequate.

PMID- 25396206
TI  - Economic inequality in eye care utilization and its determinants: a Blinder
      Oaxaca decomposition.
AB  - BACKGROUND: The current study aimed to determine eye care utilization, to assess
      the role of economic inequality in the utilization of eye care services, and to
      identify its determinants in Shahroud, North of Iran. METHODS: Of the 6,311
      invited people, 5,190 (82.24%) individuals aged 40 to 64 years old participated
      in the study. A history of a visit by an ophthalmologist or optometrist was
      considered as eye care utilization. The gap between low- and high-economic groups
      was decomposed into its determinants using the Oaxaca decomposition method.
      RESULTS: Among the participants, 16.32% [95% Confidence Intervals (CI)= 15.31
      17.33%] had never been examined by an ophthalmologist or optometrist, and 30.94%
      (95% CI= 29.69-32.20%) had not undergone an eye examination in the past 5 years.
      This negative history was significantly higher among female subjects [Odds Ratio
      (OR)= 1.79, 95% CI= 1.51-2.14], the low-economic group (OR= 2.33, 95% CI= 1.90
      2.87), the visually impaired (OR= 1.41, 95% CI= 1.05-1.90), and the uninsured
      (OR= 1.93, 95% CI= 1.45-2.58). The negative history of eye examination decreased
      with increasing in age (OR= 0.94, 95% CI= 0.93-0.96) and education (OR= 0.94, 95%
      CI= 0.92-0.96). In this study, 24.72% (95% CI= 22.30-27.14) of the low-economic
      group and 9.94% (95% CI= 8.75-11.14) of the high-economic group had no history of
      eye examination. Decomposition of the gap between the two economic groups showed
      that education and gender were the most important determinants of inequality.
      CONCLUSION: A considerable percentage of adults, even those with visual
      impairment, do not receive appropriate eye care. There is a definite economic
      inequality in the community for which poverty per se could be the major cause.

PMID- 25396207
TI  - An audit of the knowledge and attitudes of doctors towards Surgical Informed
      Consent (SIC).
AB  - BACKGROUND: The Surgical Informed Consent (SIC) is a comprehensive process that
      establishes an information-based agreement between the patient and his doctor to
      undertake a clearly outlined medical or surgical intervention. It is neither a
      casual formality nor a casually signed piece of paper. The present study was
      designed to audit the current knowledge and attitudes of doctors towards SIC at a
      tertiary care teaching hospital in Pakistan. METHODS: This cross-sectional
      qualitative investigation was conducted under the auspices of the Department of
      Medical Education (DME), Pakistan Institute of Medical Sciences (PIMS), Shaheed
      Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad over three months
      period. A 19-item questionnaire was employed for data collection. The
      participants were selected at random from the list of the surgeons maintained in
      the hospital and approached face-to-face with the help of a team of junior
      doctors detailed for questionnaire distribution among them. The target was to
      cover over 50% of these doctors by convenience sampling. RESULTS: Out of 231
      respondents, there were 32 seniors while 199 junior doctors, constituting a ratio
      of 1:6.22. The respondents variably responded to the questions regarding various
      attributes of the process of SIC. Overall, the junior doctors performed poorer
      compared to the seniors. CONCLUSION: The knowledge and attitudes of our doctors
      particularly the junior ones, towards the SIC are less than ideal. This results
      in their failure to avail this golden opportunity of doctor-patient communication
      to guide their patients through a solidly informative and legally valid SIC. They
      are often unaware of the essential preconditions of the SIC; provide incomplete
      information to their patients; and quite often do not ensure direct involvement
      of their patients in the process. Additionally they lack an understanding of
      using interactive computer-based programs as well as the concept of nocebo effect
      of informed consent.

PMID- 25396208
TI  - Use of cost-effectiveness data in priority setting decisions: experiences from
      the national guidelines for heart diseases in Sweden.
AB  - BACKGROUND: The inclusion of cost-effectiveness data, as a basis for priority
      setting rankings, is a distinguishing feature in the formulation of the Swedish
      national guidelines. Guidelines are generated with the direct intent to influence
      health policy and support decisions about the efficient allocation of scarce
      healthcare resources. Certain medical conditions may be given higher priority
      rankings i.e. given more resources than others, depending on how serious the
      medical condition is. This study investigated how a decision-making group, the
      Priority Setting Group (PSG), used cost-effectiveness data in ranking priority
      setting decisions in the national guidelines for heart diseases. METHODS: A
      qualitative case study methodology was used to explore the use of such data in
      ranking priority setting healthcare decisions. The study addressed availability
      of cost-effectiveness data, evidence understanding, interpretation difficulties,
      and the reliance on evidence. We were also interested in the explicit use of data
      in ranking decisions, especially in situations where economic arguments impacted
      the reasoning behind the decisions. RESULTS: This study showed that cost
      effectiveness data was an important and integrated part of the decision-making
      process. Involvement of a health economist and reliance on the data facilitated
      the use of cost-effectiveness data. Economic arguments were used both as a fine
      tuning instrument and a counterweight for dichotomization. Cost-effectiveness
      data were used when the overall evidence base was weak and the decision-makers
      had trouble making decisions due to lack of clinical evidence and in times of
      uncertainty. Cost-effectiveness data were also used for decisions on the
      introduction of new expensive medical technologies. CONCLUSION: Cost
      effectiveness data matters in decision-making processes and the results of this
      study could be applicable to other jurisdictions where health economics is
      implemented in decision-making. This study contributes to knowledge on how cost
      effectiveness data is used in actual decision-making, to ensure that the
      decisions are offered on equal terms and that patients receive medical care
      according their needs in order achieve maximum benefit.

PMID- 25396209
TI  - International patients on operation vacation - perspectives of patients
      travelling to Hungary for orthopaedic treatments.
AB  - BACKGROUND: The importance of cross-border healthcare, medical and health tourism
      plays a significant role in the European health policy and health management.
      After dentistry, orthopaedic treatments are the leading motivation for seeking
      care in Hungary, as patients with rheumatic and motion diseases are drawn to the
      thermal spas and well-established orthopaedic centres. This paper aims to gain
      insight into foreign patients' perspectives on their experience of having sought
      medical tourism in orthopaedic care in Hungary. METHODS: A patient survey was
      conducted in 2012 on motivations for seeking treatment abroad, orthopaedic care
      received and overall satisfaction. In addition, health professionals' interviews,
      and 17 phone interviews were conducted in 2013 with Romanian patients who had
      orthopaedic treatment in Hungary. Finally, medical records of foreign patients
      were analysed. RESULTS: The survey was completed by 115 participants - 61.1%
      females, mean age= 41.9, 87% Romanian origin. Most of the patients came to
      Hungary for orthopaedic surgeries, e.g. arthroscopy, knee/hip prosthesis or
      spinal surgery. 72.6% chose Hungary because of related to perceived better
      quality and longstanding culture of Hungarian orthopaedic care. Over 57% of
      patients reported being 'very satisfied' with care received and 41.6%
      'satisfied'. The follow-up interviews further reflected this level of
      satisfaction, therefore many respondents stating they have already recommended
      the Hungarian healthcare to others. CONCLUSION: Based on the findings, patients
      from neighbouring regions are increasingly seeking orthopaedic care in Hungary.
      Patients having orthopaedic care are highly satisfied with the quality of care,
      the whole treatment process from the availability of information to discharge
      summaries and would consider returning for further treatments.

PMID- 25396210
TI  - Exploring the relationship between accreditation and patient satisfaction - the
      case of selected Lebanese hospitals.
AB  - BACKGROUND: Patient satisfaction is one of the vital attributes to consider when
      evaluating the impact of accreditation systems. This study aimed to explore the
      impact of the national accreditation system in Lebanon on patient satisfaction.
      METHODS: An explanatory cross-sectional study of six hospitals in Lebanon.
      Patient satisfaction was measured using the SERVQUAL tool assessing five
      dimensions of quality (reliability, assurance, tangibility, empathy, and
      responsiveness). Independent variables included hospital accreditation scores,
      size, location (rural/urban), and patient demographics. RESULTS: The majority of
      patients (76.34%) were unsatisfied with the quality of services. There was no
      statistically significant association between accreditation classification and
      patient satisfaction. However, the tangibility dimension - reflecting hospital
      structural aspects such as physical facility and equipment was found to be
      associated with patient satisfaction. CONCLUSION: This study brings to light the
      importance of embracing more adequate patient satisfaction measures in the
      Lebanese hospital accreditation standards. Furthermore, the findings reinforce
      the importance of weighing the patient perspective in the development and
      implementation of accreditation systems. As accreditation is not the only driver
      of patient satisfaction, hospitals are encouraged to adopt complementary means of
      promoting patient satisfaction.

PMID- 25396211
TI  - Resource based view: a promising new theory for healthcare organizations: Comment
      on "Resource based view of the firm as a theoretical lens on the organisational
      consequences of quality improvement".
AB  - This commentary reviews a recent piece by Burton and Rycroft-Malone on the use of
      Resource Based View (RBV) in healthcare organizations. It first outlines the core
      content of their piece. It then discusses their attempts to extend RBV to the
      analysis of large scale quality improvement efforts in healthcare. Some critique
      is elaborated. The broader question of why RBV seems to be migrating into
      healthcare management research is considered. They conclude RBV is a promising
      new theory for healthcare organizations. 

PMID- 25396212
TI  - Radically questioning the principle of the least restrictive alternative: a reply
      to Nir Eyal: Comment on "Nudging by Shaming, Shaming by Nudging".
AB  - In his insightful editorial, Nir Eyal explores the connections between nudging
      and shaming. One upshot of his argument is that we should question the principle
      of the least restrictive alternative in public health and health policy. In this
      commentary, I maintain that Eyal's argument undermines only a rather implausible
      version of the principle of the least restrictive alternative and I sketch two
      reasons for rejecting the mainstream and more plausible version of this
      principle. 

PMID- 25396213
TI  - Nudging, shaming and stigmatising to improve population health: Comment on
      "Nudging by shaming, shaming by nudging".
AB  - Nudges are small, often imperceptible changes to how particular decisions present
      themselves to individuals that are meant to influence those decisions. In his
      editorial, 'Nudging by shaming, shaming by nudging', Eyal highlights links
      between nudges and feelings of shame on the part of the 'chooser'. In this
      commentary, I suggest two further distinctions between different types of shame
      based nudges that should affect our assessment of such nudges. 

PMID- 25396214
TI  - Public participation: methods matter; a response to Boaz et al.

PMID- 25396215
TI  - Essential medicines for children: an endocrine perspective.

PMID- 25396216
TI  - Small Molecule PAI-1 Functional Inhibitor Attenuates Vascular Smooth Muscle Cell
      Migration and Survival: Implications for the Therapy of Vascular Disease.

PMID- 25396217
TI  - Adult stem cells in the use of jaw bone regeneration: current and prospective
      research.
AB  - Concomitant to the increased use of dental implants to replace lost dentition,
      there is a growing need to regenerate atrophic jaw bone to allow dental implant
      placement. Current surgical techniques for jaw bone augmentation share several
      limitations, such as operator sensitivity and relatively low predictability and
      high morbidity rates. Therefore, alternative treatment approaches have been
      developed in the field of tissue engineering. Bone tissue engineering integrates
      the use of different scaffolds, growth factors, and stem cells. This method aims
      to induce bone augmentation of large bone defects by mimicking biologic processes
      that occur during embryogenesis. This review will present available sources for
      adult stem cells, the rationale for using stem cells for bone regeneration, and
      recent studies that use mesenchymal stem cells (MSC) and endothelial progenitor
      cells (EPC) to induce bone augmentation. 

PMID- 25396218
TI  - Monocyte subsets in atherosclerosis.
AB  - Endothelial dysfunction and chronic inflammation of the arterial wall
      continuously drive the development of atherosclerotic lesions. Monocytes, as
      cells of the innate immunity, are particularly involved in this process. In the
      last decade, heterogeneity of circulating monocytes has widely been acknowledged,
      and a recent consensus nomenclature subdivides classical, intermediate and
      nonclassical monocytes. Accumulating experimental and clinical data suggest a
      differential, subset-specific contribution of monocytes to the pathology of
      atherosclerosis. This review summarizes recent key findings on human and mouse
      monocyte subpopulations, specifically highlighting their phenotype, functional
      characteristics and mechanisms of recruitment at homeostatic conditions, in
      atherosclerotic vascular disease, and after acute myocardial infarction.

PMID- 25396219
TI  - Discussion of "the evolution of boosting algorithms" and "extending statistical
      boosting".
AB  - This article is part of a For-Discussion-Section of Methods of Information in
      Medicine about the papers "The Evolution of Boosting Algorithms - From Machine
      Learning to Statistical Modelling" and "Extending Statistical Boosting - An
      Overview of Recent Methodological Developments", written by Andreas Mayr and co
      authors. It is introduced by an editorial. This article contains the combined
      commentaries invited to independently comment on the Mayr et al. papers. In
      subsequent issues the discussion can continue through letters to the editor.

PMID- 25396220
TI  - Toward a formalization of the process to select IMIA Yearbook best papers.
AB  - BACKGROUND: Each year, the International Medical Informatics Association Yearbook
      recognizes significant scientific papers, labelled as "best papers", published
      the previous year in the subfields of biomedical informatics that correspond to
      the different section topics of the journal. For each section, about fifteen pre
      selected "candidate" best papers are externally peer-reviewed to select the
      actual best papers. Although based on the available literature, little is known
      about the pre-selection process. OBJECTIVE: To move toward an explicit
      formalization of the candidate best papers selection process to reduce
      variability in the literature search across sections and over years. METHODS: A
      methodological framework is proposed to build for each section topic specific
      queries tailored to PubMed and Web of Science citation databases. The two sets of
      returned papers are merged and reviewed by two independent section editors and
      citations are tagged as "discarded", "pending", and "kept". A protocolized
      consolidation step is then jointly conducted to resolve conflicts. A
      bibliographic software tool, BibReview, was developed to support the whole
      process. RESULTS: The proposed search strategy was fully applied to the Decision
      Support section of the 2013 edition of the Yearbook. For this section, 1124
      references were returned (689 PubMed-specific, 254 WoS-specific, 181 common to
      both databases) among which the 15 candidate best papers were selected.
      CONCLUSIONS: The search strategy for determining candidate best papers for an
      IMIA Yearbook's section is now explicitly specified and allows for
      reproducibility. However, some aspects of the whole process remain reviewer
      dependent, mostly because there is no characterization of a "best paper".

PMID- 25396221
TI  - Chronological bias in randomized clinical trials arising from different types of
      unobserved time trends.
AB  - BACKGROUND: In clinical trials patients are commonly recruited sequentially over
      time incurring the risk of chronological bias due to (unobserved) time trends. To
      minimize the risk of chronological bias, a suitable randomization procedure
      should be chosen. OBJECTIVES: Considering different time trend scenarios, we aim
      at a detailed evaluation of the extent of chronological bias under permuted block
      randomization in order to provide recommendations regarding the choice of
      randomization at the design stage of a clinical trial and to assess the maximum
      extent of bias for a realized sequence in the analysis stage. METHODS: For the
      assessment of chronological bias we consider linear, logarithmic and stepwise
      trends illustrating typical changes during recruitment in clinical practice. Bias
      and variance of the treatment effect estimator as well as the empirical type I
      error rate when applying the t-test are investigated. Different sample sizes,
      block sizes and strengths of time trends are considered. RESULTS: Using large
      block sizes, a notable bias exists in the estimate of the treatment effect for
      specific sequences. This results in a heavily inflated type I error for realized
      worst-case sequences and an enlarged mean squared error of the treatment effect
      estimator. Decreasing the block size restricts these effects of time trends.
      Already applying permuted block randomization with two blocks instead of the
      random allocation rule achieves a good reduction of the mean squared error and of
      the inflated type I error. Averaged over all sequences, the type I error of the t
      test is far below the nominal significance level due to an overestimated
      variance. CONCLUSIONS: Unobserved time trends can induce a strong bias in the
      treatment effect estimate and in the test decision. Therefore, already in the
      design stage of a clinical trial a suitable randomization procedure should be
      chosen. According to our results, small block sizes should be preferred, but also
      medium block sizes are sufficient to restrict chronological bias to an acceptable
      extent if other contrary aspects have to be considered (e.g. serious risk of
      selection bias). Regardless of the block size, a blocked ANOVA should be used
      because the t-test is far too conservative, even for weak time trends.

PMID- 25396222
TI  - Extraction of response waveforms of heartbeat and blood pressure to swallowing.
      Using mixed signal processing of time domain and respiratory phase domain.
AB  - BACKGROUND: Evaluating the accurate responses of the cardiovascular system to
      external stimuli is important for a deeper understanding of cardiovascular
      homeostasis. However, the responses should be distorted by the conventional time
      domain analysis when a frequency of the effect of external stimuli matches that
      of intrinsic fluctuations. OBJECTIVES: The purpose of this study is to propose a
      mixed signal processing of time domain and respiratory phase domain to extract
      the response waveforms of heartbeat and blood pressure (BP) to external stimuli
      and to clarify the physiological mechanisms of swallowing effects on the
      cardiovascular system. METHODS: Measurements were conducted on 12 healthy humans
      in the sitting and standing positions, with each subject requested to swallow
      every 30 s between expiration and inspiration. Waveforms of respiratory sinus
      arrhythmia (RSA) and respiratory-related BP variations were extracted as
      functions of the respiratory phase. Then, respiratory effects were subtracted
      from response waveforms with reference to the respiratory phase in the time
      domain. RESULTS: As a result, swallowing induced tachycardia, which peaked within
      3 s and recovered within 8 s. Tachycardia was greater in the sitting position
      than during standing. Furthermore, systolic BP and pulse pressure immediately
      decreased and diastolic BP increased coincident with the occurrence of
      tachycardia. Subsequently, systolic BP and pulse pressure recovered faster than
      the R-R interval. CONCLUSIONS: We conclude that swallowing-induced tachycardia
      arises largely from the decrease of vagal activity and the baroreflex would yield
      fast oscillatory responses in recovery.

PMID- 25396223
TI  - Revision of a loose cementless short-stem threaded femoral component using a
      standard cementless stem in a canine hip arthroplasty.
AB  - A Helica short-stemmed femoral prosthesis that was identified as being loose one
      year after implantation was revised with a standard long stem cementless BFX
      femoral prosthesis. A double pelvic osteotomy was also performed to improve the
      orientation of the stable acetabular cup. Despite complete resorption of the
      femoral neck, and a large perforation of the lateral femoral cortex, the revision
      stem did not subside or rotate. The prosthetic joint did not dislocate. At re
      evaluation two years after revision surgery, the prosthetic components were
      stable. Signs of bone ingrowth into the stem and cup were evident on radiographs.
      The dog had a seven percent greater thigh muscle girth in the limb implanted with
      the hip prosthesis compared to the contralateral limb, and was very active with
      no lameness. 

PMID- 25396224
TI  - Erosion of the medial compartment of the canine elbow: occurrence, diagnosis and
      currently available treatment options.
AB  - Erosion of the medial compartment of the elbow joint refers to full thickness
      cartilage loss with exposure of the subchondral bone (modified Outerbridge grades
      4-5) of the medial part of the humeral condyle (MHC) and the corresponding ulnar
      contact area. This finding may appear in the absence of an osteochondral fragment
      or a cartilage flap, or in combination with fragmentation of the medial coronoid
      process (MCP) or osteochondritis dissecans (OCD) of the MHC. With regard to the
      prognosis, it is important to diagnose these severe erosions. Imaging of
      cartilage lesions by means of radiography, ultrasonography, computed tomography
      or magnetic resonance imaging is challenging in dogs. In contrast, direct
      arthroscopic inspection provides detailed information about the cartilage. The
      treatment of these severe erosions is difficult because of the limited
      regenerative capacity of cartilage and presumed mechanical or physical triggering
      factors. Several conservative and surgical treatment methods have been proposed
      to treat elbows with severe cartilage defects. However, due to irreversible loss
      of cartilage, the prognosis in these cases remains guarded. 

PMID- 25396225
TI  - Ex vivo kinematic studies of a canine unlinked semi-constrained hybrid total
      elbow arthroplasty system.
AB  - OBJECTIVES: Introduction of the Sirius(r) canine total elbow arthroplasty system,
      and presentation of the results of a passive range-of-motion analysis based on ex
      vivo kinematic studies pre-and post-implantation. MATERIALS AND METHODS: Thoracic
      limbs (n = 4) of medium sized dogs were harvested by forequarter amputation.
      Plain orthogonal radiographs of each limb were obtained pre- and post
      implantation. Limbs were prepared by placement of external fixator pins and
      Kirschner wires into the humerus and radius. Each limb was secured into a custom
      made box frame and retro-reflective markers were placed on the exposed ends of
      the pins and wires. Each elbow was manually moved through five ranges-of-motion
      manoeuvres. Data collected included six trials of i) full extension to full
      flexion and ii) pronation and supination in 90 degrees  flexion; a three
      dimensional motion capture system was used to collect and analyse the data. The
      Sirius elbow prosthesis was subsequently implanted and the same measurements were
      repeated. Data sets were tested for normality. Paired t-tests were used for
      comparison of pre- and post-implantation motion parameters. RESULTS: Kinematic
      analysis showed that the range-of-motion (mean and SD) for flexion and extension
      pre-implantation was 115 degrees  +/- 6 (range: 25 degrees  to 140 degrees ). The
      range-of-motion in the sagittal plane post-implantation was 90 degrees  +/- 4
      (range: 36 degrees  to 130 degrees ) and this reduction was significant (p =
      0.0001). The ranges-of-motion (mean and SD) for supination and pronation at 90
      degrees  were 50 degrees  +/- 5, whereas the corresponding mean ranges-of-motion
      post-implantation were 38 degrees  +/- 6 (p = 0.0188). CONCLUSION: Compared to a
      normal elbow, the range-of-motion was reduced. Post-implantation, supination and
      pronation range-of-motion was significantly reduced at 90 degrees  over pre
      implantation values. CLINICAL RELEVANCE: These results provide valuable
      information regarding the effect of the Sirius system on ex vivo kinematics of
      the normal canine elbow joint. Further, this particular ex vivo model allowed for
      satisfactory and repeatable kinematic analysis.

PMID- 25396226
TI  - Risk factors for loosening of cementless threaded femoral implants in canine
      total hip arthroplasty.
AB  - OBJECTIVE: To determine the incidence and potential risk factors of femoral
      implant loosening in the canine Helica(r) total hip replacement (THR) system.
      METHOD: Sixteen dogs with a Helica THR were included. Medical records were
      reviewed for signalment and size of implants. Stem angle, stem collar to lateral
      cortex distance, tip to cortex distance, stem collar to lateral cortex distance
      at a stem angle of 150 degrees , lever arm distance, and the distance on the
      diaphysis measurements were calculated from the one year postoperative
      radiographs. Three ratios were determined from these measurements to take into
      account the size of the femur in relation to the size of the implant. Femoral
      implant loosening was identified by radiographic and clinical signs, and
      confirmed at the time of surgical explantation. Differences in the successful and
      femoral stem failure groups were compared using either a students t-test or a
      Mann Whitney test. Significance was set at p <0.003. RESULTS: Six of the 16 dogs
      had loosening of the femoral prostheses within one year post-implantation. One
      dog had evidence of a septic cause for loosening. No significant risk factors
      could be identified in this group of dogs with Helica stem loosening. CLINICAL
      SIGNIFICANCE: Helica femoral stem loosening was a common complication within one
      year post-implantation in this group of dogs. No risk factors were identified to
      potentially decrease the incidence of loosening. Therefore, due to this
      unacceptably high complication rate, the authors do not recommend this model of
      the Helica THR.

PMID- 25396227
TI  - New glioblastoma vaccine: safe and immunogenic in phase 1.

PMID- 25396228
TI  - FDA approves sublingual hay fever immunotherapeutic.

PMID- 25396229
TI  - Combining the cancer vaccine DPX-Survivac with immune modulators.

PMID- 25396230
TI  - Two meningococcal B vaccines receive FDA 'breakthrough therapy' designation.

PMID- 25396231
TI  - MERS vaccine is technically feasible, but is it commerically feasible?

PMID- 25396232
TI  - Stemline's synthetic multi-peptide cancer vaccine enters Phase 2.

PMID- 25396233
TI  - Evolution of whooping cough bacterium may reduce vaccine effectiveness.

PMID- 25396234
TI  - The life and career of Noreen M. Clark.

PMID- 25396235
TI  - Information for patients. Treatment of HER2 positive early breast cancer.

PMID- 25396236
TI  - Response: posterior cerebral artery involvement and pediatric moyamoya disease.

PMID- 25396237
TI  - [Ebola virus disease: safe management of patients with high risk infections].

PMID- 25396238
TI  - Antidepressants may be linked to implant failure risk, researchers report.

PMID- 25396239
TI  - Cost-effective procedure for trigeminal neuralgia underused, study finds.

PMID- 25396240
TI  - Abstracts from the 2014 BMT Tandem Meetings. February 26-March 2, 2014.
      Grapevine, Texas, USA.

PMID- 25396241
TI  - Response.

PMID- 25396242
TI  - Response.

PMID- 25396243
TI  - Response.

PMID- 25396244
TI  - Response.

PMID- 25396246
TI  - Neurodegenerative disease: brain windfall.

PMID- 25396245
TI  - Response.

PMID- 25396247
TI  - Turning point: Morris Birnbaum.

PMID- 25396248
TI  - [Not Available].

PMID- 25396249
TI  - [Not Available].

PMID- 25396250
TI  - [Not Available].

PMID- 25396251
TI  - [Not Available].

PMID- 25396252
TI  - [Not Available].

PMID- 25396253
TI  - [Not Available].

PMID- 25396254
TI  - [Not Available].

PMID- 25396256
TI  - Comment on "Ultrasound visualization of ingested tablets: a pilot study".

PMID- 25396255
TI  - Relative potency of varenicline or fluvoxamine to reduce responding for ethanol
      versus food depends on the presence or absence of concurrently earned food.
AB  - BACKGROUND: Varenicline, a nicotinic partial agonist, selectively reduces ethanol
      (EtOH)- versus sucrose-maintained behavior when tested in separate groups, yet
      like the indirect agonist fluvoxamine, this selectively inverts when EtOH and
      food are concurrently available. METHODS: Here, we extend these findings by
      examining varenicline and fluvoxamine effects under a multiple concurrent
      schedule where food and EtOH are concurrently available in different components:
      Component 1 where the food fixed-ratio was 25 and Component 2 where the food
      fixed-ratio was 75. The EtOH fixed-ratio was always 5. Food-maintained responding
      predominated in Component 1, while EtOH-maintained responding predominated in
      Component 2. In a second experiment, varenicline effects were assessed under a
      multiple schedule where food, then EtOH, then again food were available in
      separate 5-minute components with fixed-ratios of 5 for each reinforcement.
      RESULTS: In the multiple concurrent schedule, varenicline was more potent at
      reducing food- versus EtOH-maintained responding in both components and reduced
      EtOH-maintained responding more potently during Component 1 (when food was almost
      never earned) than in Component 2 (where food was often earned). Fluvoxamine was
      similarly potent at reducing food- and EtOH-maintained responding. Under the
      multiple schedule, varenicline, like fluvoxamine, more potently decreases EtOH-
      versus food maintained responding when only food or EtOH is available in separate
      components. CONCLUSIONS: These results demonstrate that selective effects on drug
      versus alternative-maintained behavior depend on the schedule arrangement, and
      assays in which EtOH or an alternative is the only programmed reinforcement may
      overestimate the selectivity of treatments to decrease EtOH self-administration.
      Thus selective effects obtained under one assay may not generalize to another.
      Better understanding the behavioral mechanisms responsible for these results may
      help to guide pharmaco-therapeutic development for substance use disorders.

PMID- 25396257
TI  - Using the Karolinska Sleep Questionnaire to identify obstructive sleep apnea
      syndrome in a sleep clinic population.
AB  - INTRODUCTION: In Scandinavia, portable monitoring has virtually replaced standard
      polysomnography for diagnosis of obstructive sleep apnea syndrome (OSAS). Because
      waiting times for specialized OSAS care remain long, an accurate screening tool
      to exclude low-risk patients from diagnostic testing would be valuable.
      OBJECTIVES: To examine the diagnostic accuracy of the Karolinska Sleep
      Questionnaire (KSQ) for OSAS. METHODS: Consecutive patients, 30-66 years old,
      attending a large sleep clinic in Sweden for OSAS evaluation completed the KSQ
      and underwent in-home portable monitoring and medical history evaluation. OSAS
      was defined as apnea-hypopnea index >=5 with symptoms of disease. We calculated
      sensitivity and specificity of apnea/snoring and sleepiness indices of the KSQ.
      Retrospectively, we combined six KSQ items (snoring, breathing cessations,
      disturbed sleep, etc.) and four clinical variables (age, sex, body mass index,
      smoking status) predictive of OSAS into a new instrument, which we also
      evaluated. Instrument score ranged between 0 and 21; a higher score indicated
      more severe symptoms. RESULTS: Of 103 patients, 62 were diagnosed with OSAS.
      Sensitivity and specificity of the indices were 0.56 and 0.68 (apnea/snoring),
      and 0.37 and 0.71 (sleepiness). The new instrument performed optimally at a score
      of 9. Sensitivity was 0.76 (95% confidence interval 0.63-0.86) and specificity
      0.88 (0.74-0.96). Between 19.4% and 50.5% of patients were unaware of having
      apnea/snoring symptoms. CONCLUSIONS: Diagnostic accuracy of the apnea/snoring and
      sleepiness indices for OSAS was poor but could be improved by combining clinical
      and KSQ items. The usefulness of the apnea/snoring index and the combined
      instrument was questionable because of extensive symptom unawareness.

PMID- 25396258
TI  - Malaria control and elimination, Venezuela, 1800s -1970s.
AB  - Venezuela had the highest number of human malaria cases in Latin American before
      1936. During 1891-1920,malaria was endemic to >600,000 km2 of this country;
      malaria death rates led to major population decreases during 1891-1920. No
      pathogen, including the influenza virus that caused the 1918 pandemic, caused
      more deaths than malaria during 1905-1945. Early reports of malaria eradication
      in Venezuela helped spark the world's interest in global eradication. We describe
      early approaches to malaria epidemiology in Venezuela and how this country
      developed an efficient control program and an approach to eradication.Arnoldo
      Gabaldon was a key policy maker during this development process. He directed
      malaria control in Venezuela from the late 1930s to the end of the 1970s and
      contributed to malaria program planning of the World Health Organization.We
      discuss how his efforts helped reduce the incidence of malaria in Venezuela and
      how his approach diverged from World Health Organization guidelines.

PMID- 25396259
TI  - Expectations of recovery and functional outcomes following thoracolumbar trauma:
      an evidence-based medicine process to determine what surgeons should be telling
      their patients.
AB  - OBJECT: The aim of this study was to define the expected functional and health
      related quality of life outcomes following common thoracolumbar injuries on the
      basis of consensus expert opinion and the best available literature. Patient
      expectations are primarily determined by the information provided by health care
      professionals, and these expectations have been shown to influence outcome in
      various medical and surgical conditions. This paper presents Part 2 of a
      multiphase study designed to investigate the impact of patient expectations on
      outcomes following spinal injury. Part 1 demonstrated substantial variability in
      the information surgeons are communicating to patients. Defining the expected
      outcomes following thoracolumbar injury would allow further analysis of this
      relationship and enable surgeons to more accurately and consistently inform
      patients. METHODS: Expert opinion was assembled by distributing questionnaires
      comprising 4 cases representative of common thoracolumbar injuries to members of
      the Spine Trauma Study Group (STSG). The 4 cases included a thoracolumbar
      junction burst fracture treated nonoperatively or with posterior transpedicular
      instrumentation, a low lumbar (L-4) burst fracture treated nonoperatively, and a
      thoracolumbar junction flexion-distraction injury managed with posterior fusion.
      For each case, 5 questions about expected outcomes were posed. The questions
      related to the proportion of patients who are pain free, the proportion who have
      regained full range of motion, and the patients' recreational activity
      restrictions and personal care and social life limitations, all at 1 year
      following injury, as well as the timing of return to work and length of hospital
      stay. Responses were analyzed and combined with the results of a systematic
      literature review on the same injuries to define the expected outcomes. RESULTS:
      The literature review identified 38 appropriate studies that met the preset
      inclusion criteria. Published data were available for all injuries, but not all
      outcomes were available for each type of injury. The survey was completed by 31
      (57%) of 53 surgeons representing 24 trauma centers across North America (15),
      Europe (5), India (1), Mexico (1), Japan (1) and Israel (1). Consensus expert
      opinion supplemented the available literature and was used exclusively when
      published data were lacking. For example, 1 year following cast or brace
      treatment of a thoracolumbar burst fracture, the expected outcomes include a 40%
      chance of being pain free, a 70% chance of regaining pre-injury range of motion,
      and an expected ability to participate in high-impact exercise and contact sport
      with no or minimal limitation. Consensus expert opinion predicts reemployment
      within 4-6 months. The length of inpatient stay averages 4-5 days. CONCLUSIONS:
      This synthesis of the best available literature and consensus opinion of surgeons
      with extensive clinical experience in spine trauma reflects the optimal
      methodology for determining functional prognosis after thoracolumbar trauma. By
      providing consistent, accurate information surgeons will help patients develop
      realistic expectations and potentially optimize outcomes.

PMID- 25396260
TI  - Entero-paraspinous fistula from recurrent spinal metastatic renal cell carcinoma.
AB  - The authors report a case of entero-paraspinous fistula 2 years after T-12
      corpectomy and instrumentation for spinal metastasis from renal cell carcinoma.
      The pathogenesis in the present case seems to have arisen from local recurrence
      of T-12 metastatic carcinoma in spite of radiation and corpectomy. As a result of
      previous nephrectomy and anterolateral dissection for the T-12 corpectomy, the
      jejunum adhered to the surgical site. Recurrent tumor at T-12 invaded the
      adherent small bowel loop, resulting in a fistulous communication between the
      small bowel lumen and the spinal wound. Loss of retroperitoneal fat, scarring,
      and adhesions from previous surgeries contributed to this complication by having
      the jejunum close to the T-12 corpectomy site, and eventually to its invasion by
      recurrent tumor. Avoidance of such a complication is difficult; however, total
      excision of the spinal malignancy, and when possible, creating a barrier cuff of
      fascia or fat around the spine to protect abdominal contents, are potential
      solutions. 

PMID- 25396261
TI  - Effects of cross-linked high-molecular-weight hyaluronic acid on epidural
      fibrosis: experimental study.
AB  - OBJECT: Epidural fibrosis is nonphysiological scar formation, usually at the site
      of neurosurgical access into the spinal canal, in the intimate vicinity of and
      around the origin of the radicular sheath. The formation of dense fibrous tissue
      causes lumbar and radicular pain. In addition to radicular symptoms, the
      formation of scar tissue may cause problems during reoperation. The authors aimed
      to investigate the effects of cross-linked high-molecular-weight hyaluronic acid
      (HA), an HA derivative known as HA gel, on the prevention of epidural fibrosis by
      using histopathological and biochemical parameters. METHODS: Fifty-six adult
      female Sprague-Dawley rats were evaluated. The rats were divided into 4 groups.
      Rats in the sham group (n = 14) underwent laminectomy and discectomy and received
      no treatment; rats in the control group (n = 14) underwent laminectomy and
      discectomy and received 0.9% NaCl treatment in the surgical area; rats in the HA
      group (n = 14) received HA treatment at the surgical area after laminectomy and
      discectomy; and rats in the HA gel group (n = 14) underwent laminectomy and
      discectomy in addition to receiving treatment with cross-linked high-molecular
      weight HA in the surgical area. All rats were decapitated after 4 weeks, and the
      specimens were evaluated histopathologically and biochemically. The results were
      statistically compared using the Mann-Whitney U-test. RESULTS: Compared with the
      sham and control groups, the HA and HA gel groups showed significantly lower
      fibroblast cell density and tissue hydroxyproline concentrations (p < 0.05).
      There was statistically significant lower dural adhesion and foreign-body
      reaction between the control and HA gel groups (p < 0.05). Granulation tissue and
      epidural fibrosis were significantly lower in the HA and HA gel groups compared
      with the sham group (p < 0.05). There were no significant differences in any
      histopathological parameters or biochemical values between Groups 3 and 4 (p >
      0.05). CONCLUSIONS: Cross-linked high-molecular-weight HA had positive effects on
      the prevention of epidural fibrosis and the reduction of fibrotic tissue density.
      The efficacy of this agent should also be verified in further experimental and
      clinical studies.

PMID- 25396262
TI  - Neighbourhood socio-economic position, late presentation and outcomes in people
      living with HIV in Switzerland.
AB  - OBJECTIVES: Inequalities and inequities in health are an important public health
      concern. In Switzerland, mortality in the general population varies according to
      the socio-economic position (SEP) of neighbourhoods. We examined the influence of
      neighbourhood SEP on presentation and outcomes in HIV-positive individuals in the
      era of combination antiretroviral therapy (cART). METHODS: The neighbourhood SEP
      of patients followed in the Swiss HIV Cohort Study (SHCS) 2000-2013 was obtained
      on the basis of 2000 census data on the 50 nearest households (education and
      occupation of household head, rent, mean number of persons per room). We used Cox
      and logistic regression models to examine the probability of late presentation,
      virologic response to cART, loss to follow-up and death across quintiles of
      neighbourhood SEP. RESULTS: A total of 4489 SHCS participants were included.
      Presentation with advanced disease [CD4+ cell count <200 cells/MUl or AIDS] and
      with AIDS was less common in neighbourhoods of higher SEP: the age and sex
      adjusted odds ratio (OR) comparing the highest with the lowest quintile of SEP
      was 0.71 [95% confidence interval (95% CI) 0.58-0.87] and 0.59 (95% CI 0.45
      0.77), respectively. An undetectable viral load at 6 months of cART was more
      common in the highest than in the lowest quintile (OR 1.52; 95% CI 1.14-2.04).
      Loss to follow-up, mortality and causes of death were not associated with
      neighbourhood SEP. CONCLUSION: Late presentation was more common and virologic
      response to cART less common in HIV-positive individuals living in neighbourhoods
      of lower SEP, but in contrast to the general population, there was no clear trend
      for mortality.

PMID- 25396263
TI  - Opportunities for improving the efficiency of paediatric HIV treatment
      programmes.
AB  - OBJECTIVES: To conduct two economic analyses addressing whether to: routinely
      monitor HIV-infected children on antiretroviral therapy (ART) clinically or with
      laboratory tests; continue or stop cotrimoxazole prophylaxis when children become
      stabilized on ART. DESIGN AND METHODS: The ARROW randomized trial investigated
      alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in
      1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of
      implementation analyses were undertaken. Scenario analyses investigated whether
      laboratory monitoring (CD4 tests for efficacy monitoring;
      haematology/biochemistry for toxicity) could be tailored and targeted to be
      delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and
      non-endemic settings. RESULTS: Using all trial data, clinical monitoring
      delivered similar health outcomes to routine laboratory monitoring, but at a
      reduced cost, so was cost-effective. Continuing cotrimoxazole improved health
      outcomes at reduced costs. Restricting routine CD4 monitoring to after 52 weeks
      following ART initiation and removing toxicity testing was associated with an
      incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year
      (QALY) across all age groups, but was much lower for older children (12+ years at
      initiation; incremental cost-effectiveness ratio = $769/QALY). Committing
      resources to improve cotrimoxazole implementation appears cost-effective. A
      healthcare system that could pay $600/QALY should be willing to spend up to $12.0
      per patient-year to ensure continued provision of cotrimoxazole. CONCLUSION:
      Clinically driven monitoring of ART is cost-effective in most circumstances.
      Routine laboratory monitoring is generally not cost-effective at current prices,
      except possibly CD4 testing amongst adolescents initiating ART. Committing
      resources to ensure continued provision of cotrimoxazole in health facilities is
      more likely to represent an efficient use of resources.

PMID- 25396265
TI  - The role of HIV-specific antibody-dependent cellular cytotoxicity in HIV
      prevention and the influence of the HIV-1 Vpu protein.
AB  - There is growing interest in the role of anti-HIV antibody-dependent cellular
      cytotoxicity (ADCC) antibodies in the prevention and control of HIV infection.
      Passive transfer studies in macaques support a role for the Fc region of
      antibodies in assisting in the prevention of simian-human immunodeficiency virus
      (SHIV) infection. The Thai RV144 HIV-1 vaccine trial induced anti-HIV ADCC
      antibodies that may have played a role in the partial protection observed.
      Several observational studies support a role for ADCC antibodies in slowing HIV
      disease progression. However, HIV evolves to escape ADCC antibodies and chronic
      HIV infections causes dysfunction of effector cells such as natural killer (NK)
      cells that mediate the ADCC functions. Further, four recent studies show that the
      HIV-1 Vpu protein, by promoting release of virions, reduces the capacity of ADCC
      antibodies to recognize HIV-infected cells. The review dissects some of the
      recent research on HIV-specific ADCC antibodies and discusses mechanisms to
      further harness ADCC antibodies in the prevention and control of HIV infection. 

PMID- 25396267
TI  - Improving associative memory in older adults with unitization.
AB  - We examined if unitization inherent preexperimentally could reduce the
      associative deficit in older adults. In Experiment 1, younger and older adults
      studied compound word (CW; e.g., store keeper) and noncompound word (NCW; e.g.,
      needle birth) pairs. We found a reduction in the age-related associative deficit
      such that older but not younger adults showed a discrimination advantage for CW
      relative to NCW pairs on a yes-no associative recognition test. These results
      suggest that CW compared to NCW word pairs provide schematic support that older
      adults can use to improve their memory. In Experiment 2, reducing study time in
      younger adults decreased associative recognition performance, but did not produce
      a discrimination advantage for CW pairs. In Experiment 3, both older and younger
      adults showed a discrimination advantage for CW pairs on a two-alternative forced
      choice recognition test, which encourages greater use of familiarity. These
      results suggest that test format influenced young adults' use of familiarity
      during associative recognition of unitized pairs, and that older adults rely more
      on familiarity than recollection for associative recognition. Unitization of
      preexperimental associations, as in CW pairs, can alleviate age-related
      associative deficits. 

PMID- 25396266
TI  - Effects of randomized rosuvastatin compared with placebo on bone and body
      composition among HIV-infected adults.
AB  - BACKGROUND: Statins have a beneficial effect on bone mineral density (BMD) and
      lean mass in some studies of HIV-uninfected adults; however, this has never been
      investigated in the setting of HIV infection. DESIGN: HIV-infected individuals on
      stable antiretroviral therapy with a low-density lipoprotein cholesterol level of
      130 mg/dl or less and evidence of heightened immune activation or inflammation
      were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. METHODS:
      This was a prespecified interim analysis at 48 weeks. Between-group and within
      group differences were compared; multivariable regression models were
      constructed. RESULTS: Seventy-two individuals were randomized to statin therapy
      and 75 to placebo. Modest 48-week relative increases in trochanter BMD [0.9%; 95%
      confidence interval (95% CI) -0.9 to 0.6] and total hip BMD (0.6%; 95% CI 0.0
      1.1) in the statin arm were significantly greater than placebo (P < 0.05). The
      relationship between statin use and total hip BMD change was robust to adjustment
      of age, sex, race and smoking status (P = 0.02) and strengthened by inclusion of
      baseline (P = 0.01) and week 48 change in soluble tumour necrosis factor-alpha
      receptor (sTNFR)-1 (P = 0.009). Relative increases in total body, trunk and limb
      fat were similar between statin and placebo arms (P >= 0.58). Although a
      significant gain in leg lean mass was seen in the statin arm, this was not
      significantly different compared with placebo (P = 0.36). CONCLUSION: The
      improvements seen in total hip BMD after 48 weeks of rosuvastatin therapy support
      further potential benefits of statin therapy in HIV, beyond a reduction of
      cardiovascular risk.

PMID- 25396268
TI  - Protein malnutrition attenuates bone anabolic response to PTH in female rats.
AB  - PTH is indicated for the treatment of severe osteoporosis. Elderly osteoporotic
      patients frequently suffer from protein malnutrition, which may contribute to
      bone loss. It is unknown whether this malnutrition may affect the response to
      PTH. Therefore, the aim of the present study was to assess whether an isocaloric
      low-protein (LP) diet may influence the bone anabolic response to intermittent
      PTH in 6-month-old female rats. Six-month-old female rats were either pair fed an
      isocaloric LP diet (2.5% casein) or a normal-protein (NP) diet (15% casein) for 2
      weeks. The rats continued on their respective diet while being treated with 5- or
      40-MUg/kg recombinant human PTH amino-terminal fragment 1-34 (PTH-[1-34]) daily,
      or with vehicle for 4 weeks. At the end of this period, areal bone mineral
      density, bone mineral content, microstructure, and bone strength in axial
      compression of proximal tibia or 3-point bending for midshaft tibia tests were
      measured. Blood was collected for the determination of IGF-I and osteocalcin.
      After 4 weeks of PTH-(1-34), the dose-dependent increase of proximal tibia bone
      mineral density, trabecular microstructure variables, and bone strength was
      attenuated in rats fed a LP diet as compared with rats on a NP intake. At the
      level of midshaft tibia cortical bone, PTH-(1-34) exerted an anabolic effect only
      in the NP but not in the LP diet group. Protein malnutrition was associated with
      lower IGF-I levels. Protein malnutrition attenuates the bone anabolic effects of
      PTH-(1-34) in rats. These results suggest that a sufficient protein intake should
      be recommended for osteoporotic patients undergoing PTH therapy. 

PMID- 25396269
TI  - A closer look at evolution: Variants (SNPs) of genes involved in skin
      pigmentation, including EXOC2, TYR, TYRP1, and DCT, are associated with 25(OH)D
      serum concentration.
AB  - Vitamin D deficiency is common in the Caucasian population and is associated with
      increased incidence and unfavorable outcome of many diseases, including various
      types of cancer, infectious, cardiovascular, and autoimmune diseases. Individual
      factors that predispose for a person's vitamin D status, such as skin type, have
      been identified, but limited data exist on genetic determinants of serum 25
      hydroxyvitamin D (25[OH]D) concentration. We have tested the hypothesis that
      variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin
      pigmentation are predictive of serum 25(OH)D levels. Serum 25(OH)D and SNPs (n =
      960) related to genes with relevance for skin pigmentation (tyrosinase [TYR], TYR
      related protein 1 [TYRP1], dopachrome tautomerase [DCT], oculocutaneous albinism
      II [OCA2], two pore segment channel 2 [TPCN2], solute carrier family 24 A4
      [SLC24A4], solute carrier family 45 A2 [SLC45A2], agouti signalling peptide
      [ASIP], cyclic AMP-dependent transcription factor [ATF1], microphthalmia
      associated transcription factor [MITF], proopiomelanocortin [POMC], cAMP
      dependent protein kinase catalytic subunit beta [PRKACB], cAMP-dependent protein
      kinase catalytic subunit gamma [PRKACG], cAMP-dependent protein kinase type I
      alpha regulatory subunit [PRKAR1A], cAMP-dependent protein kinase type II-alpha
      regulatory subunit [PRKAR2A], cAMP-dependent protein kinase type II-beta
      regulatory subunit [PRKAR2B], tubulin beta-3 chain/melanocortin receptor 1
      [TUBB3/MC1R], Cadherin-1 [CDH1], catenin beta 1 [CTNNB1], Endothelin 1 [EDN1],
      endothelin 3 [EDN3], endothelin receptor type B [EDNRB], fibroblast growth factor
      2 [FGF2], KIT, KIT ligand [KITLG], nerve growth factor [NGF], interferon
      regulatory factor 4 [IRF4], exocyst complex component 2 [EXOC2], and tumor
      protein 53 [TP53]) were analyzed in a cohort of participants of the Ludwigshafen
      Risk and Cardiovascular Health Study (n = 2970). A total of 46 SNPs were
      associated (P <.05) with lower or higher serum 25(OH)D levels as compared with
      the total cohort (median, 15.5 ng/mL). Although 1 SNP in the EXOC2 gene reached
      the aimed significance level after correction for multiple comparisons (false
      discovery rate) and was associated with a Delta25(OH)D value more than 5.00
      ng/mL, 11 SNPs located in the TYR (n = 4), PRKACG (n = 1), EDN1 (n = 3), TYRP1 (n
      = 1), and microphthalmia-associated transcription factor (n = 2) genes reached
      the aimed significance level after false discovery rate correction but were not
      associated with Delta25(OH)D value more than 5.00 ng/mL. We conclude that
      variants of genes involved in skin pigmentation are predictive of serum 25(OH)D
      levels in the Caucasian population. Our data indicate that out of the variants in
      29 different genes analyzed, variants of 11 genes, including EXOC2, TYR, and
      TYRP1, have the highest impact on vitamin D status. Our results have a
      fundamental importance to understand the role of sunlight, skin pigmentation, and
      vitamin D for the human evolution.

PMID- 25396270
TI  - Trends in office-based care for reproductive-aged women according to physician
      specialty: a ten-year study.
AB  - BACKGROUND: The anticipated increase in access to health care has prompted an
      interest in where women go for their office-based care. The objectives of this
      study were to examine which types of office site are chosen by reproductive-aged
      women for their health care and to compare the reasons for their visits among
      these sites. METHODS: This descriptive study involved an analysis of national
      data from the Medical Expenditure Panel Survey between 2002 and 2011. We
      restricted the analysis to a nationally representative group of women between 19
      and 39 years old (n=45,133). Interviews with patients were used to identify the
      patient's demographics, type of physician seen, and main reason for each self
      reported office visit (n=208,814). RESULTS: One in four women did not go to a
      physician's office each year. Nearly all who sought some sort of office-based
      care went to family physicians, ob-gyns, or a combination. For the women who did
      go to a physician's office, going only to a family physician's office was most
      common (42.6%). In contrast, 28.6% of these women visited only an ob-gyn office,
      and an additional 21.5% went to offices of a family physician or general
      internist as well as an ob-gyn physician. Visits only to offices of ob-gyns were
      highest among women who were married and healthy. Compared with family physicians
      or internists, the percentages of office visits to an ob-gyn were more likely for
      pregnancy (57.0% vs. 2.8%), about the same for a general check-up (23.6% vs.
      29.2%), and less for diagnosis or treatment (13.7% vs. 55.5%). Those who went to
      ob-gyn offices were most apt to return for several visits per year. CONCLUSION:
      Almost all health care sought by women aged 19 to 39 in a year is to ob-gyns or
      family physicians, and significant sharing of care exists across these provider
      groups. While most visits to family physicians were for diagnosis or treatment,
      the majority of visits to ob-gyn were for pregnancy-related care.

PMID- 25396272
TI  - Mechanical circulatory support of a univentricular Fontan circulation with a
      continuous axial-flow pump in a piglet model.
AB  - Despite the significant contribution of the Fontan procedure to the therapy of
      complex congenital heart diseases, many patients progress to failure of their
      Fontan circulation. The use of ventricular assist devices to provide circulatory
      support to these patients remains challenging. In the current study, a continuous
      axial-flow pump was used to support a univentricular Fontan circulation. A
      modified Fontan circulation (atrio-pulmonary connection) was constructed in six
      Yorkshire piglets (8-14 kg). A Dacron conduit (12 mm) with two branches was
      constructed to serve as a complete atrio-pulmonary connection without the use of
      cardiopulmonary bypass. The Impella pump was inserted into the conduit through an
      additional Polytetrafluoroethylene (PTFE) graft in five animals. Hemodynamic data
      were collected for 6 hours under the supported Fontan circulation. The control
      animal died after initiating the Fontan circulation independent of resuscitation.
      Four pump supported animals remained hemodynamically stable for 6 hours with pump
      speeds between 18,000 rpm and 22,000 rpm (P1-P3). Oxygen saturation was
      maintained between 95% and 100%. Normal organ perfusion was illustrated by blood
      gas analysis and biochemical assays. A continuous axial-flow pump can be used for
      temporal circulatory support to the failing Fontan circulation as "bridge" to
      heart transplantation or recovery. 

PMID- 25396273
TI  - Extracorporeal life support as a bridge to heart transplantation: importance of
      organ failure in recipient selection.
AB  - We investigated the utility of comprehensive scoring systems for organ failure
      compared with the duration of extracorporeal life support (ECLS) in predicting
      survival after heart transplantation. From November 2004 to August 2013, 25 adult
      patients ultimately underwent heart transplantation while on ECLS. We did not
      include patients who were younger than 18 years old or patients with
      extracorporeal ventricular assist devices. Seven patients (28%) died within 1
      year after transplantation. The areas under the curve (receiver operating
      characteristics (ROC), optimal cut-off value) of the sequential organ-failure
      assessment and the model for end-stage liver disease score modified by the United
      Network for Organ Sharing scores were 0.794 (13) and 0.825 (24), respectively. In
      multivariate analysis, the model for end-stage liver disease score modified by
      the United Network for Organ Sharing score was independently prognostic
      regardless of the duration of ECLS and sequential organ-failure assessment score.

PMID- 25396274
TI  - Device exchange in HeartMate II recipients: long-term outcomes and risk of
      thrombosis recurrence.
AB  - Successful long-term use of the HeartMate II (HM II) left ventricular assist
      device has become commonplace but may be complicated by mechanical failure,
      infection, or thrombosis necessitating device exchange (DE). A subcostal approach
      to device exchange with motor exchange only is less traumatic, but long-term
      outcomes have not been reported. A retrospective chart review of all patients who
      required HM II to HM II device exchange at our institution was conducted. Of the
      232 HM II patients implanted between January 2008 and July 2013, 28 required 36
      device exchanges during a follow-up of 33.72 +/- 17.25 months. The Kaplan-Meier 1
      year survival was 63% for sternotomy exchanges and 100% for subcostal exchanges.
      Twenty-one exchanges were performed for initial or recurring device thrombosis.
      Although there was no difference in the risk of subsequent thrombosis after
      subcostal versus sternotomy exchange, the overall risk of recurring device
      thrombosis after device exchange for the same was high (31%). HM II device
      exchange via the subcostal approach has excellent short- and long-term outcomes.
      Device exchange performed for thrombosis is associated with a high recurrence
      risk irrespective of surgical approach. 

PMID- 25396275
TI  - Spectroscopic and morphological characterization of inflow cannulas of left
      ventricular assist devices.
AB  - Despite the consistent clinical data on the positive effects of left ventricular
      assist devices (LVADs) in the treatment of refractory heart failure,
      unfortunately these devices yet show some limitations such as the risk of stroke,
      infection, and device malfunction. The complex interplay between blood and the
      foreign material has a major role in the occurrence of these complications and
      biocompatibility of the inflow cannula would be pivotal in these terms. In this
      study, we carried out an in-depth physicochemical characterization of two
      commercially available LVADs by means of field emission gun scanning electron
      microscopy, energy dispersive X-ray, and X-ray photoelectron spectra. Our results
      show that, despite both pumps share the same physicochemical concepts, major
      differences can be identified in the surface nature, morphology, and chemical
      composition of their inflow cannulas. 

PMID- 25396276
TI  - Suction prevention and physiologic control of continuous flow left ventricular
      assist devices using intrinsic pump parameters.
AB  - The risk for left ventricular (LV) suction during left ventricular assist devices
      (LVAD) support has been a clinical concern. Current development efforts suggest
      LVAD suction prevention and physiologic control algorithms may require chronic
      implantation of pressure or flow sensors, which can be unreliable because of
      baseline drift and short lifespan. To overcome this limitation, we designed a
      sensorless suction prevention and physiologic control (eSPPC) algorithm that only
      requires LVAD intrinsic parameters (pump speed and power). Two gain-scheduled,
      proportional-integral controllers maintain a differential pump speed (DeltaRPM)
      above a user-defined threshold to prevent LV suction while maintaining an average
      reference differential pressure (DeltaP) between the LV and aorta. DeltaRPM is
      calculated from noisy pump speed measurements that are low-pass filtered, and
      DeltaP is estimated using an extended Kalman filter. Efficacy and robustness of
      the eSPPC algorithm were evaluated in silico during simulated rest and exercise
      test conditions for 1) excessive DeltaP setpoint (ES); 2) rapid eightfold
      increase in pulmonary vascular resistance (PVR); and 3) ES and PVR. Simulated
      hemodynamic waveforms (LV pressure and volume; aortic pressure and flow) using
      only intrinsic pump parameters showed the feasibility of our proposed eSPPC
      algorithm in preventing LV suction for all test conditions. 

PMID- 25396277
TI  - Robust synthesis of N-sulfonylazetidine building blocks via ring contraction of
      alpha-bromo N-sulfonylpyrrolidinones.
AB  - A simple and robust one-pot nucleophilic addition-ring contraction of alpha-bromo
      N-sulfonylpyrrolidinones has been achieved toward alpha-carbonylated N
      sulfonylazetidines. In the presence of potassium carbonate, various nucleophiles,
      such as alcohols, phenols or anilines, have been efficiently incorporated into
      the azetidine derivatives. Moreover, the alpha-bromopyrrolidinone precursors
      could be selectively obtained in good yields by monobromination of cheap and
      easily available N-sulfonyl-2-pyrrolidinone derivatives. 

PMID- 25396278
TI  - Selective and efficient photocatalytic CO2 reduction to CO using visible light
      and an iron-based homogeneous catalyst.
AB  - Converting CO2 into valuable compounds using sunlight as the energy input and an
      earth-abundant metal complex as the catalyst is an exciting challenge related to
      contemporary energy issues as well as to climate change. By using an inexpensive
      organic photosensitizer under visible-light excitation (lambda > 400 nm) and a
      substituted iron(0) tetraphenylporphyrin as a homogeneous catalyst, we have been
      able to generate carbon monoxide from CO2 selectively with high turnover numbers.
      Sustained catalytic activity over a long time period (t > 50 h) did not lead to
      catalyst or sensitizer deactivation. A catalytic mechanism is proposed. 

PMID- 25396279
TI  - Sleep Patterns, Sleep Disturbances, and Associated Factors Among Chinese Urban
      Kindergarten Children.
AB  - This study aimed to characterize sleep patterns and disturbances among Chinese
      urban kindergarten children and examine potentially associated factors.
      Caregivers of 513 children (47.96% male) aged 3-6 years (mean age = 4.46, SD =
      0.9) completed the Children's Sleep Habits Questionnaire (CSHQ) and the Strengths
      and Difficulties Questionnaire (SDQ). Almost 80% (78.8%) of the children scored
      above the original CSHQ cutoff point for global sleep disturbance. Regression
      analysis indicated that child's age, and the presence of emotional problems,
      hyperactivity and peer problems, cosleeping, and interparental inconsistency of
      attitudes toward child rearing accounted for significant variance in the CSHQ
      total score (R(2) = 22%). These findings indicate that there is an apparently
      high prevalence of sleep disturbances in Chinese urban kindergarten children; and
      sleep disturbances are associated with both child-related and parenting practice
      variables. 

PMID- 25396280
TI  - Ferrocenyl-functionalized Sn/Se and Sn/Te complexes: synthesis, reactivity,
      optical, and electronic properties.
AB  - An adamantane-shaped, ferrocenyl-substituted tin selenide complex, [(FcSn)4Se6]
      (1; Fc = ferrocenyl), and a ferrocenyl-substituted tin telluride five-membered
      ring, [(Fc2Sn)3Te2] (2), were obtained upon treatment of FcSnCl3 with K2E (E =
      Se, Te). Complex 1 further reacts with Na2S.9H2O and [Cu(PPh3)3Cl] to form a
      ternary complex, [(CuPPh3)6(S/Se)6(SnFc)2] (3). We discuss structures, optical
      and electrochemical properties as well as Mossbauer spectra. 

PMID- 25396281
TI  - Radiotherapeutic bandage based on electrospun polyacrylonitrile containing
      holmium-166 iron garnet nanoparticles for the treatment of skin cancer.
AB  - Radiation therapy is used as a primary treatment for inoperable tumors and in
      patients that cannot or will not undergo surgery. Radioactive holmium-166
      ((166)Ho) is a viable candidate for use against skin cancer. Nonradioactive
      holmium-165 ((165)Ho) iron garnet nanoparticles have been incorporated into a
      bandage, which, after neutron-activation to (166)Ho, can be applied to a tumor
      lesion. The (165)Ho iron garnet nanoparticles ((165)HoIG) were synthesized and
      introduced into polyacrylonitrile (PAN) polymer solutions. The polymer solutions
      were then electrospun to produce flexible nonwoven bandages, which are stable to
      neutron-activation. The fiber mats were characterized using scanning electron
      microscopy, transmission electron microscopy, powder X-ray diffraction, Fourier
      transform infrared spectroscopy, thermogravimetric analysis and inductively
      coupled plasma mass spectrometry. The bandages are stable after neutron
      activation at a thermal neutron-flux of approximately 3.5 * 10(12)
      neutrons/cm(2).s for at least 4 h and 100  degrees C. Different amounts of
      radioactivity can be produced by changing the amount of the (165)HoIG
      nanoparticles inside the bandage and the duration of neutron-activation, which is
      important for different stages of skin cancer. Furthermore, the radioactive
      bandage can be easily manipulated to irradiate only the tumor site by cutting the
      bandage into specific shapes and sizes that cover the tumor prior to neutron
      activation. Thus, exposure of healthy cells to high energy beta-particles can be
      avoided. Moreover, there is no leakage of radioactive material after neutron
      activation, which is critical for safe handling by healthcare professionals
      treating skin cancer patients. 

PMID- 25396282
TI  - Individual reactions to stress predict performance during a critical aviation
      incident.
AB  - BACKGROUND: Understanding the influence of stress on human performance is of
      theoretical and practical importance. An individual's reaction to stress predicts
      their subsequent performance; with a "challenge" response to stress leading to
      better performance than a "threat" response. However, this contention has not
      been tested in truly stressful environments with highly skilled individuals.
      Furthermore, the effect of challenge and threat responses on attentional control
      during visuomotor tasks is poorly understood. DESIGN: Thus, this study aimed to
      examine individual reactions to stress and their influence on attentional
      control, among a cohort of commercial pilots performing a stressful flight
      assessment. METHODS: Sixteen pilots performed an "engine failure on take-off"
      scenario, in a high-fidelity flight simulator. Reactions to stress were indexed
      via self-report; performance was assessed subjectively (flight instructor
      assessment) and objectively (simulator metrics); gaze behavior data were captured
      using a mobile eye tracker, and measures of attentional control were subsequently
      calculated (search rate, stimulus driven attention, and entropy). RESULTS:
      Hierarchical regression analyses revealed that a threat response was associated
      with poorer performance and disrupted attentional control. CONCLUSION: The
      findings add to previous research showing that individual reactions to stress
      influence performance and shed light on the processes through which stress
      influences performance.

PMID- 25396283
TI  - Tracking and discrete dual task performance with different spatial stimulus
      response mappings.
AB  - The effect of spatial compatibility on dual-task performance for various display
      control configurations was studied using a tracking task and a discrete four
      choice response task. A total of 36 participants took part in this study, and
      they were asked to perform the primary tracking task while at the same time to
      respond to an occasional signal. Different levels of compatibility between the
      stimuli and responses of the discrete response task were found to lead to
      different degrees of influence on the tracking task. However, degradation of
      performance was observed for both tasks, which was probably due to resource
      competition for the visual and spatial resources required for simultaneous task
      operation and required for bimanual responses. No right-left prevalence effect
      for the spatial compatibility task was observed in this study, implying that the
      use of unimanual two-finger responses may not provide the right conditions for a
      significant effect in the horizontal right-left dimension. PRACTITIONER SUMMARY:
      The effect of spatial compatibility in multiple display-control configurations
      was examined in a dual-task paradigm. The analyses of keen competition for visual
      and spatial resources in processing the dual tasks under different degrees of
      stimulus-response compatibility provide useful ergonomics design implications and
      recommendations for visual interfaces requiring frequent visual scanning.

PMID- 25396284
TI  - Morphological learning in a novel language: A cross-language comparison.
AB  - Being able to extract and interpret the internal structure of complex word forms
      such as the English word dance+r+s is crucial for successful language learning.
      We examined whether the ability to extract morphological information during word
      learning is affected by the morphological features of one's native tongue.
      Spanish and Finnish adult participants performed a word-picture associative
      learning task in an artificial language where the target words included a suffix
      marking the gender of the corresponding animate object. The short exposure phase
      was followed by a word recognition task and a generalization task for the suffix.
      The participants' native tongues vary greatly in terms of morphological
      structure, leading to two opposing hypotheses. On the one hand, Spanish speakers
      may be more effective in identifying gender in a novel language because this
      feature is present in Spanish but not in Finnish. On the other hand, Finnish
      speakers may have an advantage as the abundance of bound morphemes in their
      language calls for continuous morphological decomposition. The results support
      the latter alternative, suggesting that lifelong experience on morphological
      decomposition provides an advantage in novel morphological learning. 

PMID- 25396285
TI  - Arsenic and lead in foods: a potential threat to human health in Bangladesh.
AB  - The non-carcinogenic and carcinogenic risk of arsenic and lead to adults and
      children via daily dietary intake of food composites in Bangladesh was estimated.
      The target hazard quotients (THQs), hazard index (HI) and target carcinogenic
      risk (TR) were calculated to evaluate the non-carcinogenic and carcinogenic
      health risk from arsenic and lead. Most of the individual food composites contain
      a considerable amount of arsenic and lead. The highest mean concentrations of
      arsenic were found in cereals (0.254 mg kg-1 fw) and vegetables (0.250 mg kg-1
      fw), and lead in vegetables (0.714 mg kg-1 fw) and fish (0.326 mg kg-1 fw). The
      results showed the highest THQs of arsenic in cereals and lead in vegetables for
      both adults and children which exceeded the safe limit (> 1) indicating that
      cereals and vegetables are the main food items contributing to the potential
      health risk. The estimated TR from ingesting dietary arsenic and lead from most
      of the foods exceeded 10-6, indicating carcinogenic risks for all adult people of
      the study area.

PMID- 25396286
TI  - Electrospun regenerated cellulose nanofibrous membranes surface-grafted with
      polymer chains/brushes via the atom transfer radical polymerization method for
      catalase immobilization.
AB  - In this study, an electrospun regenerated cellulose (RC) nanofibrous membrane
      with fiber diameters of ~200-400 nm was prepared first; subsequently, 2
      hydroxyethyl methacrylate (HEMA), 2-dimethylaminoethyl methacrylate (DMAEMA), and
      acrylic acid (AA) were selected as the monomers for surface grafting of polymer
      chains/brushes via the atom transfer radical polymerization (ATRP) method.
      Thereafter, four nanofibrous membranes (i.e., RC, RC-poly(HEMA), RC-poly(DMAEMA),
      and RC-poly(AA)) were explored as innovative supports for immobilization of an
      enzyme of bovine liver catalase (CAT). The amount/capacity, activity, stability,
      and reusability of immobilized catalase were evaluated, and the kinetic
      parameters (Vmax and Km) for immobilized and free catalase were determined. The
      results indicated that the respective amounts/capacities of immobilized catalase
      on RC-poly(HEMA) and RC-poly(DMAEMA) nanofibrous membranes reached 78 +/- 3.5 and
      67 +/- 2.7 mg g(-1), which were considerably higher than the previously reported
      values. Meanwhile, compared to that of free CAT (i.e., 18 days), the half-life
      periods of RC-CAT, RC-poly(HEMA)-CAT, RC-poly(DMAEMA)-CAT, and RC-poly(AA)-CAT
      were 49, 58, 56, and 60 days, respectively, indicating that the storage stability
      of immobilized catalase was also significantly improved. Furthermore, the
      immobilized catalase exhibited substantially higher resistance to temperature
      variation (tested from 5 to 70  degrees C) and lower degree of sensitivity to pH
      value (tested from 4.0 and 10.0) than the free catalase. In particular, according
      to the kinetic parameters of Vmax and Km, the nanofibrous membranes of RC
      poly(HEMA) (i.e., 5102 MUmol mg(-1) min(-1) and 44.89 mM) and RC-poly(DMAEMA)
      (i.e., 4651 MUmol mg(-1) min(-1) and 46.98 mM) had the most satisfactory
      biocompatibility with immobilized catalase. It was therefore concluded that the
      electrospun RC nanofibrous membranes surface-grafted with 3-dimensional
      nanolayers of polymer chains/brushes would be suitable/ideal as efficient
      supports for high-density and reusable enzyme immobilization.

PMID- 25396287
TI  - Maintaining human health at the border of Taiwan.
AB  - Because international travel is now more frequent and convenient, communicable
      diseases that occur in one region can be transmitted to another area within a few
      hours. For this reason, many efforts have been undertaken in Taiwan to establish
      a comprehensive border quarantine system to protect against imported diseases
      that may threaten the health of the population. According to the International
      Health Regulations (2005), decades of development strategies for border
      quarantine have covered not only routine practices and specific measures for
      handling a pandemic but also have drawn attention to the development of core
      capacities at designated points of entry. However, as a result of the rapidly
      increasing number of points of entry, changes in transportation patterns, and the
      emergence of diseases, current border quarantine practice is being challenged to
      maintain human resources and the efficacy of entry screening. It is therefore
      critical to reexamine border quarantine strategies that will fit future needs and
      national conditions. This article reviews the current border health practices in
      Taiwan and discusses 5 key challenges to be further considered and improved. The
      findings can serve as a guide for further policy reform in Taiwan and other
      countries. 

PMID- 25396288
TI  - Successful collaborative model for STEMI care between a STEMI-referral and a
      STEMI receiving center.
AB  - BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI)
      greatly benefit from a rapid door-to-balloon (D2B) time. For hospitals without a
      catheterization laboratory, it is imperative to establish partnerships with a
      STEMI receiving center (SRC). STEMI systems of care have been established to
      facilitate these relationships to improve rapid reperfusion. We describe the
      experience and benefits of such a relationship. METHODS: A partnership between
      our 2 institutions was established in April 2011. Saint Anthony Hospital (SAH) of
      Chicago is an inner city hospital with interventional cardiologists on staff, but
      no catheterization laboratory. Before the partnership, STEMI patients were
      transferred 8 miles to a percutaneous coronary intervention (PCI) hospital on the
      city's north side. Rush University Medical Center (RUMC) is an academic medical
      center with 24/7/365 PCI capability. SAH decided that a transfer relationship
      with a closer SRC would benefit patient care. The following steps were taken:
      both hospitals signed a STEMI transfer agreement for STEMI transfers regardless
      of insurance status; an education process occurred at both hospitals; agreement
      that transferred patients would follow-up at the STEMI referring hospital (SAH);
      a contract with a single ambulance provider was signed; a simple STEMI protocol
      was adopted. RESULTS: In 2010, SAH saw 20 patients with STEMI. Average time from
      patient arrival to leaving the emergency department (ED) [Door-in-Door-out
      (DIDO)] was 83 minutes, these times were not tracked carefully; approximate
      transfer time to SRC was 25 minutes; Door1-2-Balloon (D12B) time was not
      recorded. Since the new protocol, 44 patients transferred to RUMC for PCI to
      date. Median (inclusive minimum, maximum) time from ED arrival (D1) at referral
      hospital to SRC (D2) was 52 minutes (56, 192) for all PCI cases; 11 patients
      transferred did not have PCI; 1 patient expired upon arrival; and median time to
      first PCI device (D12B) was 86 minutes (53-167). DISCUSSION: Streamlining STEMI
      patient care to reduce D2B is a major priority. We have demonstrated that
      establishing a transfer program between a STEMI-Referral Hospital (SRH) and SRC
      can markedly improve time to reperfusion. This approach has resulted in D12B that
      match or exceeds the D2B for nontransfer patients at most STEMI-receiving
      hospitals.

PMID- 25396289
TI  - "No culprit" ST-elevation myocardial infarction: role of cardiac magnetic
      resonance imaging.
AB  - Patients with presumed ST-elevation myocardial infarction (STEMI) have no clear
      culprit artery in approximately 10-15% of cases. We examined the value of cardiac
      magnetic resonance (CMR) for diagnosis in patients with "no culprit" STEMI. Data
      from a comprehensive prospective registry of STEMI patients were reviewed from
      March 2003 to December 2009. "No culprit" patients were followed for diagnosis
      and clinical outcome. CMR was performed at the discretion of the attending
      cardiologist. Of 2728 consecutive presumed STEMI patients, 412 (15%) had no clear
      culprit artery. Of these, 202 (49%) had abnormal cardiac biomarkers with a
      definitive diagnosis in 157 (78%). Diagnoses in this group included myocardial
      infarction without a culprit lesion (24%), myopericarditis (22%), and stress
      cardiomyopathy (21%). In 210 (51%) patients with normal biomarkers, only 84 (40%)
      received a definitive diagnosis. Diagnoses in this group included myopericarditis
      (27%), noncardiac causes (21%), and cardiomyopathy (14%). CMR was performed in
      123 (30%) "no culprit" patients. Patients who had CMR were more likely to have a
      definitive diagnosis than those who did not (95/123 [77%] vs. 144/289 [50%];
      P=0.01). In particular, "no culprit" patients with abnormal biomarkers were more
      likely to have a definitive diagnosis with CMR. CMR led to a diagnosis different
      from the presumptive clinical diagnosis in 53% of all cases. CMR is a valuable
      diagnostic tool to improve diagnostic accuracy in patients with "no culprit"
      STEMI.

PMID- 25396290
TI  - Hypertension and atrial fibrillation: prognostic aspects of troponin elevations
      in clinical practice.
AB  - BACKGROUND: Hypertension and atrial fibrillation (AFib) frequently coexist in
      clinical practice. However, it is unclear whether this association per se or in
      combination with coronary artery disease (CAD) is a predictor of adverse
      outcomes. AIM: The aim of this study is to recognize and treat CAD in patients
      with hypertension and AFib. METHODS: Patients with long-standing hypertension and
      recent-onset AFib (lasting <=48 hours) were enrolled and managed with standard
      care regardless of the presence of troponin elevations (e-TnI) (group 1, n=636,
      2010-2011 years) or managed with tailored-care including echocardiography and
      stress testing when presenting with e-TnI (group 2, n=663, 2012-2013 years).
      ENDPOINT: The composite of ischemic vascular events including stroke, acute
      coronary syndrome, revascularization, and death at the 6-month follow-up.
      RESULTS: Out of 1299 patients enrolled, those with e-TnI (56 and 57 in groups 2
      and 1, respectively, P=0.768) were more likely to admit in group 2 vs. group 1
      (21 vs. 32, respectively, P=0.060), and less likely to undergo stress testing in
      group 2 vs. group 1 (15 vs. 1, respectively, P<0.001). Twenty-one patients in
      group 2 were admitted with positive stress testing (n=9) or high e-TnI (n=12;
      1.04+/-1.98 ng/mL); conversely 35 were discharged with negative stress testing
      (n=6) or very-low e-TnI (n=29; 0.27+/-0.22 ng/mL). Finally, 7 patients vs. 1, in
      groups 2 and 1, respectively, underwent revascularization (P=0.032), and 3 vs. 12
      reached the endpoint (P=0.024). On multivariate analysis, e-TnI, known CAD and
      age were predictors of the endpoint. CONCLUSIONS: In patients with hypertension,
      AFib, and e-TnI, tailored-care inclusive of echocardiography and stress testing
      succeeded in recognizing and treating CAD avoiding adverse events without
      increase in admissions.

PMID- 25396291
TI  - Impact of troponin testing in noncardiac admissions.
AB  - BACKGROUND: There is little data to support Troponin I (TNI) use in the
      management of noncardiac patients. We studied the use of TNI in patients on our
      gastroenterology service, to determine whether there was a change in management
      as a result of TNI testing. METHODOLOGY: Patients admitted from September 2011 to
      June 2012 to our gastroenterology service who had TNI performed were included.
      Data collected included symptoms, cardiovascular risk factors, medical treatment,
      and testing. RESULTS: Sixty-three of 295 patients had a positive TNI. The mean
      length of stay was significantly longer with a positive troponin (180 vs. 108
      hours, P<0.001). Age, hypertension, diabetes, coronary artery disease, and
      chronic kidney disease were associated with a positive TNI. Cardiac consultation
      and echocardiography were performed in a higher proportion of TNI positive
      patients (P<0.0001). There were no statistically significant changes in treatment
      with clopidogrel, beta-blockers, angiotensin converting enzyme inhibitors, or
      statins between both groups. CONCLUSIONS: TNI testing in patients admitted to the
      gastroenterology service was associated with increased length of stay and
      echocardiography, without any change in management. This study supports adherence
      to national guidelines for the use of TNI, to reduce TNI testing and length of
      hospital stay.

PMID- 25396292
TI  - Gender disparities in stress test utilization in chest pain unit patients based
      upon the ordering physician's gender.
AB  - OBJECTIVE: Physicians' gender may impact test utilization in the diagnosis of
      acute cardiovascular disease. We sought to determine if physician gender affected
      stress test utilization by patient gender in a low-risk chest pain observation
      unit. METHODS: This was a retrospective consecutive cohort study of patients
      admitted to a chest pain unit in a large volume academic urban emergency
      department (ED). Inclusion criteria were age>18, American Heart Association low
      to-intermediate risk, electrocardiogram nondiagnostic for acute coronary
      syndrome, and negative initial troponin I. Exclusion criteria were age>75 with a
      history of coronary artery disease, active comorbid medical problems, or
      inability to obtain stress testing in the ED for any reason. T-tests were used
      for univariate comparisons and logistic regression was used to estimate odds
      ratios (ORs) for receiving testing based on physician gender, controlling for
      race, insurance, and Thrombolysis In Myocardial Infarction (TIMI) score. RESULTS:
      Three thousand eight hundred and seventy-three index visits were enrolled during
      a 2.5-year period. Mean age was 53+/-20, 55% (95% CI, 53-56%) were female. There
      was no difference in overall stress utilization based upon physician gender
      (P=0.28). However, after controlling for other variables, male physicians had
      significantly lower odds of stress testing female patients (ORM, 0.82; 95% CI,
      0.68-0.99), whereas no difference was found in female physicians (ORF, 0.80; 95%
      CI, 0.57-1.14). CONCLUSIONS: Male physicians appear less likely to utilize stress
      testing in female patients even after controlling for objective clinical
      variables, including TIMI score. Although adverse outcomes are uncommon in this
      patient cohort, further investigation into provider-specific practice patterns
      based on patient gender is necessary.

PMID- 25396293
TI  - Pharmacodynamic and clinical implications of switching between P2Y12 receptor
      antagonists: considerations for practice.
AB  - Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist, either
      clopidogrel or the newer more potent agents prasugrel or ticagrelor, is standard
      therapy in patients receiving a coronary stent and those with a recent acute
      coronary syndrome. Switching antiplatelet drug regimen may be required in some
      patients for efficacy, safety, adherence, and cost considerations. However, there
      are potential concerns when switching from one agent to another that gaps in
      effective antiplatelet inhibition could lead to thrombotic events, and overlap of
      agents might cause excessive platelet inhibition thereby increasing the risk of
      bleeding. This review considers pharmacodynamic and clinical data to guide
      clinicians when switching between antiplatelet drugs is considered. Loading dose
      of the new agent should be considered in nearly all situations to avoid any
      possible gap in adequate platelet inhibition, as overlap of the 2 agents is
      unlikely to result in bleeding in excess of that with the more potent drug. 

PMID- 25396294
TI  - Creating a virtual coronary care unit in the community in 2014 Dr. Raymond D.
      Bahr founder, Society of Cardiovascular Patient Care and Early Heart Attack Care.

PMID- 25396295
TI  - Recommendations for the evaluation and management of observation services: a
      consensus white paper: the Society of Cardiovascular Patient Care.
AB  - Observation Services (OS) was founded by emergency physicians in an attempt to
      manage "boarding" issues faced by emergency departments throughout the United
      States. As a result, OS have proven to be an effective strategy in reducing costs
      and decreasing lengths of stay while improving patient outcomes. When OS are
      appropriately leveraged for maximum efficiency, patients presenting to emergency
      departments with common disease processes can be effectively treated in a timely
      manner. A well-structured observation program will help hospitals reduce the
      number of inappropriate, costly inpatient admissions while avoiding the potential
      of inappropriate discharges. Observation medicine is a complicated
      multidimensional issue that has generated much confusion. This service is
      designed to provide the best possible patient care in a value-based purchasing
      environment where quality, cost, and patient satisfaction must continually be
      addressed. Observation medicine is a service not a status. Therefore, patients
      are admitted to the service as outpatients no matter whether they are placed in a
      virtual or dedicated observation unit. The key to a successful observation
      program is to determine how to maximize efficiencies. This white paper provides
      the reader with the foundational guidance for observational services. It defines
      how to set up an observational service program, which diagnoses are most
      appropriate for admission, and what the future holds. The goal is to help care
      providers from any hospital deliver the most appropriate level of treatment, to
      the most appropriate patient, in the most appropriate location while controlling
      costs. 

PMID- 25396296
TI  - Synthesis and biological activity of two C-7 methyl analogues of vitamin D.
AB  - Two novel vitamin D analogues of the hormone 1alpha,25-(OH)2D3 modified at C-7,
      namely, 7-methyl-1alpha,25-(OH)2D3 (12) and 7-methyl-1alpha,25-(OH)2-19-nor-D3
      (26), were synthesized and biologically evaluated to gain further insights into
      the structure-function relationships of vitamin D. Key steps in the synthesis of
      12 include the functionalization at C-7 by an efficient regioselective
      hydrostannylation of an allene precursor, and the construction of the triene
      framework by a palladium-catalyzed intramolecular cyclization-Suzuki-Miyaura
      coupling cascade. Since the calcitriol analogue 12 was prone to conversion into
      its previtamin D form by thermal equilibration, the corresponding 19-nor-compound
      26 was also synthesized. The diene moiety of compound 26 was constructed by a
      modified Julia coupling. UV data as well as X-ray analysis indicate that
      introduction of the methyl group at C-7 results in a significant deviation from
      planarity of the 5,7-diene moiety. The new vitamin D analogues 12 and 26 retained
      good VDR binding ability. 

PMID- 25396298
TI  - Immune evasion in ebolavirus infections.
AB  - Ebola virus (EBOV) infects humans as well as several animal species. It can lead
      to a highly lethal disease, with mortality rates approaching 90% in primates.
      Recent advances have deepened our understanding of how this virus is able to
      prevent the development of protective immune responses. The EBOV genome encodes
      eight proteins, four of which were shown to interact with the host in ways that
      counteract the immune response. The viral protein 35 (VP35) is capable of capping
      dsRNA and interacts with IRF7 to prevent detection of the virus by immune cells.
      The main role of the soluble glycoprotein (sGP) is still unclear, but it is
      capable of subverting the anti-GP1,2 antibody response. The GP1,2 protein has
      shown anti-tetherin activity and the ability to hide cell-surface proteins.
      Finally, VP24 interferes with the production of interferons (IFNs) and with IFN
      signaling in infected cells. Taken together, these data point to extensive
      adaptation of EBOV to evade the immune system of dead end hosts. While our
      understanding of the interactions between the human and viral proteins increases,
      details of those interactions in other hosts remain largely unclear and represent
      a gap in our knowledge.

PMID- 25396297
TI  - Variance predicts salience in central sensory processing.
AB  - Information processing in the sensory periphery is shaped by natural stimulus
      statistics. In the periphery, a transmission bottleneck constrains performance;
      thus efficient coding implies that natural signal components with a predictably
      wider range should be compressed. In a different regime--when sampling
      limitations constrain performance--efficient coding implies that more resources
      should be allocated to informative features that are more variable. We propose
      that this regime is relevant for sensory cortex when it extracts complex features
      from limited numbers of sensory samples. To test this prediction, we use central
      visual processing as a model: we show that visual sensitivity for local multi
      point spatial correlations, described by dozens of independently-measured
      parameters, can be quantitatively predicted from the structure of natural images.
      This suggests that efficient coding applies centrally, where it extends to higher
      order sensory features and operates in a regime in which sensitivity increases
      with feature variability.

PMID- 25396299
TI  - Genetic analysis of zebrafish gonadotropin (FSH and LH) functions by TALEN
      mediated gene disruption.
AB  - Vertebrate reproduction is controlled by two gonadotropins (FSH and LH) from the
      pituitary. Despite numerous studies on FSH and LH in fish species, their
      functions in reproduction still remain poorly defined. This is partly due to the
      lack of powerful genetic approaches for functional studies in adult fish. This
      situation is now changing with the emergence of genome-editing technologies,
      especially Transcription Activator-Like Effector Nuclease (TALEN) and Clustered
      Regularly Interspaced Short Palindromic Repeats (CRISPR). In this study, we
      deleted the hormone-specific beta-genes of both FSH and LH in the zebrafish using
      TALEN. This was followed by a phenotype analysis for key reproductive events,
      including gonadal differentiation, puberty onset, gametogenesis, final
      maturation, and fertility. FSH-deficient zebrafish (fshb(-/-)) were surprisingly
      fertile in both sexes; however, the development of both the ovary and testis was
      significantly delayed. In contrast, LH-deficient zebrafish (lhb(-/-)) showed
      normal gonadal growth, but the females failed to spawn and were therefore
      infertile. Using previtellogenic follicles as the marker, we observed a
      significant delay of puberty onset in the fshb mutant but not the lhb mutant
      females. Interestingly, FSH seemed to play a role in maintaining the female
      status because we repeatedly observed sexual reversal in the fshb mutant. Neither
      the fshb nor lhb mutation alone seemed to affect gonadal differentiation;
      however, the double mutation of the two genes led to all males, although the
      development of the testis was significantly delayed. In summary, our data
      confirmed some well-known functions of FSH and LH in fish while also providing
      evidence for novel functions, which would be difficult to reveal using
      traditional biochemical and physiological approaches. 

PMID- 25396301
TI  - Prevalence of asymptomatic vertebral fractures in late-onset Pompe disease.
AB  - CONTEXT: Bone fragility and low bone mass have been reported in small case series
      of patients with Pompe disease with severely reduced muscle strength or
      immobilization. OBJECTIVE: Our objective was to determine the prevalence of
      morphometric vertebral fractures and to evaluate bone mass in adults with late
      onset Pompe disease. DESIGN: We conducted a multicenter cross-sectional
      observational study from August 2012 to December 2013. STUDY SETTING: All
      subjects were outpatients referred to University Referral Centers. PATIENTS:
      PATIENTS included 22 late-onset Pompe disease patients with progressive proximal
      myopathy and minimal respiratory involvement without other diseases affecting
      bone mass. MAIN OUTCOME MEASURE: The prevalence of morphometric vertebral
      fractures was systematically assessed by semiquantitative analysis of lateral
      spine x-rays (T4-L5). RESULTS: A high prevalence of morphometric vertebral
      fractures was found. At least 1 vertebral fracture was present in 17 of 22
      patients (77%). All vertebral fractures were asymptomatic. Bone mineral density
      was normal in 36.5% of the patients, whereas 36.5% were osteopenic and 27% were
      osteoporotic in at least 1 site. Fracture prevalence was independent of muscular
      and respiratory functional parameters and of genotype. CONCLUSIONS: Our data show
      for the first time that asymptomatic and atraumatic vertebral fractures occur
      frequently in late-onset Pompe disease patients without a significant impairment
      of bone mass. Screening for asymptomatic vertebral fractures should be routinely
      performed in Pompe disease irrespective of the disease severity. Fracture risk
      should be confirmed in longitudinal studies.

PMID- 25396302
TI  - Transforming growth factor-beta superfamily in obstructive lung diseases. more
      suspects than TGF-beta alone.
AB  - Asthma and chronic obstructive pulmonary disease are respiratory disorders and a
      major global health problem with increasing incidence and severity. Genes
      originally associated with lung development could be relevant in the pathogenesis
      of chronic obstructive pulmonary disease/asthma, owing to either an early-life
      origin of adult complex diseases or their dysregulation in adulthood upon
      exposure to environmental stressors (e.g., smoking). The transforming growth
      factor (TGF)-beta superfamily is conserved through evolution and is involved in a
      range of biological processes, both during development and in adult tissue
      homeostasis. TGF-beta1 has emerged as an important regulator of lung and immune
      system development. However, considerable evidence has been presented for a role
      of many of the other ligands of the TGF-beta superfamily in lung pathology,
      including activins, bone morphogenetic proteins, and growth differentiation
      factors. In this review, we summarize the current knowledge on the mechanisms by
      which activin, bone morphogenetic protein, and growth differentiation factor
      signaling contribute to the pathogenesis of obstructive airway diseases. 

PMID- 25396300
TI  - Minireview: microRNA function in pancreatic beta cells.
AB  - MicroRNAs are small noncoding ribonucleotides that regulate mRNA translation or
      degradation and have major roles in cellular function. MicroRNA (miRNA) levels
      are deregulated or altered in many diseases. There is overwhelming evidence that
      miRNAs also play an important role in the regulation of glucose homeostasis and
      thereby may contribute to the establishment of diabetes. MiRNAs have been shown
      to affect insulin levels by regulating insulin production, insulin exocytosis,
      and endocrine pancreas development. Although a large number of miRNAs have been
      identified from pancreatic beta-cells using various screens, functional studies
      that link most of the identified miRNAs to regulation of pancreatic beta-cell
      function are lacking. This review focuses on miRNAs with important roles in
      regulation of insulin production, insulin secretion, and beta-cell development,
      and will discuss only miRNAs with established roles in beta-cell function. 

PMID- 25396303
TI  - Control of metamorphic buffer structure and device performance of In(x)Ga(1-x)As
      epitaxial layers fabricated by metal organic chemical vapor deposition.
AB  - Using a step-graded (SG) buffer structure via metal-organic chemical vapor
      deposition, we demonstrate a high suitability of In0.5Ga0.5As epitaxial layers on
      a GaAs substrate for electronic device application. Taking advantage of the
      technique's precise control, we were able to increase the number of SG layers to
      achieve a fairly low dislocation density (~10(6) cm(-2)), while keeping each
      individual SG layer slightly exceeding the critical thickness (~80 nm) for strain
      relaxation. This met the demanded but contradictory requirements, and even
      offered excellent scalability by lowering the whole buffer structure down to 2.3
      MUm. This scalability overwhelmingly excels the forefront studies. The effects of
      the SG misfit strain on the crystal quality and surface morphology of
      In0.5Ga0.5As epitaxial layers were carefully investigated, and were correlated to
      threading dislocation (TD) blocking mechanisms. From microstructural analyses,
      TDs can be blocked effectively through self-annihilation reactions, or hindered
      randomly by misfit dislocation mechanisms. Growth conditions for avoiding phase
      separation were also explored and identified. The buffer-improved, high-quality
      In0.5Ga0.5As epitaxial layers enabled a high-performance, metal-oxide
      semiconductor capacitor on a GaAs substrate. The devices displayed remarkable
      capacitance-voltage responses with small frequency dispersion. A promising
      interface trap density of 3 * 10(12) eV(-1) cm(-2) in a conductance test was also
      obtained. These electrical performances are competitive to those using lattice
      coherent but pricey InGaAs/InP systems. 

PMID- 25396304
TI  - An age-period-cohort analysis of cancer incidence among the oldest old, Utah 1973
      2002.
AB  - We used age-period-cohort (APC) analyses to describe the simultaneous effects of
      age, period, and cohort on cancer incidence rates in an attempt to understand the
      population dynamics underlying their patterns among those aged 85+. Data from the
      Utah Cancer Registry (UCR), the US Census, the National Center for Health
      Statistics (NCHS), and the National Cancer Institute's Surveillance, Epidemiology
      and End Results (SEER) programme were used to generate age-specific estimates of
      cancer incidence at ages 65-99 from 1973 to 2002 for Utah. Our results showed
      increasing cancer incidence rates up to the 85-89 age group followed by declines
      at ages 90-99 when not confounded by the separate influences of period and cohort
      effects. We found significant period and cohort effects, suggesting the role of
      environmental mechanisms in cancer incidence trends between the ages of 85 and
      100. 

PMID- 25396306
TI  - Approaching the patient with an anterior mediastinal mass: a guide for
      clinicians.
AB  - Anterior mediastinal masses are relatively uncommon, include a wide variety of
      entities, and often pose a diagnostic challenge for clinicians. In this article,
      available data is assembled in a clinically oriented manner to develop a
      structured approach to evaluation of these patients. Attention to age and gender,
      combined with identification of certain radiographic and clinical
      characteristics, allows a presumptive diagnosis to be established in most
      patients. This structure efficiently guides what additional workup is needed. 

PMID- 25396307
TI  - Approaching the patient with an anterior mediastinal mass: a guide for
      radiologists.
AB  - Mediastinal masses are relatively uncommon, yet include a large variety of
      entities. Some tumors can be diagnosed with confidence based on imaging alone;
      others when a typical appearance is combined with the right clinical
      presentation. A structured approach for radiologists is presented to facilitate
      evaluation of patients with anterior mediastinal tumors. The approach focuses
      first on the more common tumors and on imaging features that strongly suggest a
      particular diagnosis. Discussion with the clinician can be very helpful in
      formulating a presumptive diagnosis. This article also discusses that
      confirmatory imaging or biopsy tests are most beneficial in particular
      situations. 

PMID- 25396308
TI  - A practical guide from the International Thymic Malignancy Interest Group (ITMIG)
      regarding the radiographic assessment of treatment response of thymic epithelial
      tumors using modified RECIST criteria.
AB  - Measuring tumor response to chemotherapy is important for both clinical decision
      making and for multi-institutional studies. Thymoma tends to spread along the
      pleura: a challenge for accurate tumor measurement. Inaccurate and inconsistent
      tumor measurements often compromise results from clinical trials that are
      dependent on identifying response rate and progression-free survival. In this
      article, we sought to provide a practical guide on how to measure thymoma by the
      International Thymic Malignancy Interest Group's recommendations for standard
      outcome measures. The aim of this article is to clarify this measuring technique,
      lead to consistency between institutions, and minimize intra- and interobserver
      variability. 

PMID- 25396309
TI  - Histologic classification of thymoma: a practical guide for routine cases.

PMID- 25396310
TI  - State of the art of genetic alterations in thymic epithelial tumors.
AB  - The rapid advent of technology in recent years has resulted in a substantial
      increase in our knowledge of the molecular underpinnings of thymic epithelial
      tumors. In addition to previously described chromosomal aberrations and
      alterations in DNA methylation, genome sequencing has helped unravel hitherto
      unknown mutations in these tumors. Attempts are also being made to develop gene
      signatures to help in the identification of patients likely to benefit from
      adjuvant therapy. Some of the recently identified genetic alterations have the
      potential to serve as targets for biological therapy, thus opening newer avenues
      for treatment of thymic epithelial tumors and increasing the number of effective
      options for treatment of recurrent or refractory disease. 

PMID- 25396311
TI  - Alterations of the immune system in thymic malignancies.
AB  - Normal thymic architecture is essential for the proper development of T
      lymphocytes. Immature T-cell progenitors enter the thymus where through
      interactions with cortical and medullary thymic epithelial cells (TECs) they
      undergo positive and negative selection and become competent cells that do not
      react with self-antigens. This process requires normal thymic architecture,
      expression of major histocompatibility complex (MHC) class II, and normal
      expression of the autoimmune regulator (AIRE) gene. Thymomas are rare neoplasms
      of the TECs that often generate lymphocytes that mature into CD4+ and CD8+ T
      lymphocytes. However, several abnormalities have been described in thymomas that
      may affect normal T-cell development: the tumor architecture is distorted,
      neoplastics expresses less MHC class II, most thymomas do not express AIRE, and
      production of T-regulator cells is decreased. Thymomas are associated with a
      variety of autoimmune disorders often linked to T-cell-mediated autoimmunity.
      Myasthenia gravis, the most common autoimmune disorder associated with thymoma
      patients, is present in 30% of patients with thymoma. Several theories attempt to
      explain the association of immune disorders with thymomas. These different
      theories are based on failure of positive and negative selection of T-lymphocytes
      and on autoimmunizing mechanisms in an AIRE-poor environment in the thymus. The
      finding that immunosurveillance against cancer may be impaired before the
      diagnosis of thymoma may challenge current theories and suggest a more complex
      defect in T-lymphocyte maturation. It is likely that a combination of mechanisms
      is responsible for immune disorders in patients with thymoma. More investigation
      is needed to clarify the basic mechanisms responsible for immune disorders in
      patients with thymoma. 

PMID- 25396313
TI  - Overview.

PMID- 25396312
TI  - Paraneoplastic disorders in thymoma patients.
AB  - Thymic malignancy is often associated with paraneoplastic neurological diseases
      (PNDs) and recognition of these disorders is important for physicians who treat
      these patients. The most common thymoma-associated PNDs are myasthenia gravis
      (MG), acquired neuromyotonia (Isaacs' syndrome), encephalitis, Morvan's syndrome,
      and myositis. Diagnosis of these disorders is complex but often aided by testing
      for specific autoantibodies, including those to the acetylcholine receptor for MG
      and to contactin-associated protein-like 2, protein of the voltage-gated
      potassium channel complex, in patients with acquired neuromyotonia, Morvan's
      syndrome, or encephalitis. Patients who manifest these disorders should be
      screened for thymoma at diagnosis, and worsening of these PNDs may be associated
      with recurrent thymoma. These disorders can cause profound disability but usually
      respond to immunotherapy, and often improve with thymoma treatment. Close
      cooperation among a team of specialists is required to take proper care of these
      patients. 

PMID- 25396318
TI  - A modern definition of mediastinal compartments.
AB  - Division of the mediastinum into compartments is used to help narrow the
      differential diagnosis of newly detected mediastinal masses, to assist in
      planning biopsy and surgical procedures, and to facilitate communication among
      clinicians of multiple disciplines. Several traditional mediastinal division
      schemes exist based upon arbitrary landmarks on the lateral chest radiograph. We
      describe a modern, computed tomography-based mediastinal division scheme, which
      has been accepted by the International Thymic Malignancy Interest Group as a new
      standard. This clinical classification defines a prevascular (anterior), a
      visceral (middle), and a paravertebral (posterior) compartment, with anatomic
      boundaries defined clearly by computed tomography. It is our intention that this
      definition be used in the reporting of clinical cases and the design of
      prospective clinical trials. 

PMID- 25396317
TI  - The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node
      Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM
      Classification of Malignant Tumors.
AB  - Although the presence of nodal disease is prognostic in thymic malignancy, the
      significance of the extent of nodal disease has yet to be defined. Lymph node
      dissection has not been routinely performed, and there is currently no node map
      defined for thymic malignancy. To establish a universal language for reporting as
      well as characterize the staging of this disease more accurately, an empiric node
      map is proposed here. This was developed using prior classification systems,
      series reporting specifics of nodal involvement, anatomical studies of lymphatic
      drainage, and preexisting node maps of the chest as defined by the International
      Association for the Study of Lung Cancer and the neck as defined by the American
      Academy of Otolaryngology-Head and Neck Surgery and the American Society for Head
      and Neck Surgery. The development of this node map was a joint effort by the
      International Thymic Malignancy Interest Group and the Thymic Domain of the IASLC
      Staging and Prognostic Factors Committee. It was reviewed and subsequently
      approved by the members of ITMIG. This map will be used as an adjunct to define
      node staging as part of a universal stage classification for thymic malignancy.
      As more data are gathered using definitions set forth by this node map, a
      revision may be undertaken in the future. 

PMID- 25396315
TI  - The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposals for the T
      Component for the forthcoming (8th) edition of the TNM classification of
      malignant tumors.
AB  - Despite longstanding recognition of thymic epithelial neoplasms, there is no
      official American Joint Committee on Cancer/Union for International Cancer
      Control stage classification. This article summarizes proposals for
      classification of the T component of stage classification for use in the 8th
      edition of the tumor, node, metastasis classification for malignant tumors. This
      represents the output of the International Association for the Study of Lung
      Cancer and the International Thymic Malignancies Interest Group Staging and
      Prognostics Factor Committee, which assembled and analyzed a worldwide database
      of 10,808 patients with thymic malignancies from 105 sites. The committee
      proposes division of the T component into four categories, representing levels of
      invasion. T1 includes tumors localized to the thymus and anterior mediastinal
      fat, regardless of capsular invasion, up to and including infiltration through
      the mediastinal pleura. Invasion of the pericardium is designated as T2. T3
      includes tumors with direct involvement of a group of mediastinal structures
      either singly or in combination: lung, brachiocephalic vein, superior vena cava,
      chest wall, and phrenic nerve. Invasion of more central structures constitutes
      T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium,
      trachea, and esophagus. Size did not emerge as a useful descriptor for stage
      classification. This classification of T categories, combined with a
      classification of N and M categories, provides a basis for a robust tumor, node,
      metastasis classification system for the 8th edition of American Joint Committee
      on Cancer/Union for International Cancer Control stage classification. 

PMID- 25396319
TI  - Transdiagnostic CBT treatment of co-morbid anxiety and depression in an older
      adult: single case experimental design.
AB  - BACKGROUND: Despite the prevalence of co-morbid anxiety and depression in older
      adults, evaluation of suitable clinical models is rare. AIMS: This study tested
      the acceptability and effectiveness of a transdiagnostic approach to treating co
      morbid anxiety and depression in an older adults in a routine clinical setting.
      METHOD: In an A/B single case experimental design, a patient completed five daily
      ideographic measures of anxiety and depression across baseline and treatment and
      the HADS at five time points over time, including 3-month follow-up. The 8
      session treatment was transdiagnostic CBT informed by the Unified Protocol.
      RESULTS: All sessions were attended. Significant baseline-treatment improvements
      were found for daily structure, mood, confidence and worry, with large associated
      effect sizes. The HADS showed that the patient met recovery criteria by the end
      of treatment, with some evidence of anxious relapse at follow-up. CONCLUSION:
      Transdiagnostic CBT offers promise as a treatment approach to mixed anxiety and
      depression in older adults. The model needs to be further tested using more
      rigorous and suitably powered methodologies.

PMID- 25396314
TI  - The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an
      evidence-based stage classification system for the forthcoming (8th) edition of
      the TNM classification of malignant tumors.
AB  - A universal and consistent stage classification system, which describes the
      anatomic extent of a cancer, provides a foundation for communication and
      collaboration. Thymic epithelial malignancies have seen little progress, in part
      because of the lack of an official system. The International Association for the
      Study of Lung Cancer and the International Thymic Malignancies Interest Group
      assembled a large retrospective database, a multispecialty international
      committee and carried out extensive analysis to develop proposals for the 8th
      edition of the stage classification manuals. This tumor, node, metastasis (TNM)
      based system is applicable to all types of thymic epithelial malignancies. This
      article summarizes the proposed definitions of the T, N, and M components and
      describes how these are combined into stage groups. This represents a major step
      forward for thymic malignancies. 

PMID- 25396316
TI  - The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposals for the N and
      M components for the forthcoming (8th) edition of the TNM classification of
      malignant tumors.
AB  - Stage classification is an important underpinning of management of patients with
      cancer, and rests on a combination of three components: T for tumor extent, N for
      nodal involvement, and M for more distant metastases. This article details an
      initiative to develop proposals for the first official stage classification
      system for thymic malignancies for the 8th edition of the stage classification
      manuals. Specifically, the results of analysis of a large database and the
      considerations leading to the proposed N and M components are described. Nodal
      involvement is divided into an anterior (N1) and a deep (N2) category. Metastases
      can involve pleural or pericardial nodules (M1a) or intraparenchymal pulmonary
      nodules or metastases to distant sites (M1b). 

PMID- 25396321
TI  - The use of amniotic membrane/umbilical cord in first metatarsophalangeal joint
      cheilectomy: a comparative bilateral case study.
AB  - Hallux rigidus is marked by degenerative osteoarthritis of the first
      metatarsophalangeal (MTP) joint with pain and stiffness in the joint, with first
      ray plantarflexion and dorsiflexion, swelling and inflammation surrounding the
      first MTP joint, and reduced sagittal plane motion. Treatment of mild cases of
      hallux rigidus focuses on conservative, nonsurgical treatments such as rigid
      orthotic devices, physical therapy, pain relievers, and corticosteroid
      injections. Hallux rigidus recalcitrant to conservative management can be treated
      with dorsal cheilectomy to palliate pain at extremes of motion. Post-cheilectomy
      scarring and stiffness of the joint result in a diminished arc of motion over
      time. This clinical problem is not readily addressed by current treatment
      methods. Amniotic membrane/umbilical cord has the potential to modulate adult
      wound healing by suppressing stromal cellular-based inflammation and reducing
      scarring. Cryopreserved amniotic membrane/umbilical cord (AM/UC) tissue has been
      successfully used for minimizing postoperative inflammation, pain, and adhesion
      formation following various soft tissue reconstructive procedures, particularly
      in ophthalmology. Recently, the therapeutic potential of cryopreserved AM/UC has
      been expanded for use in lower extremity reconstructive procedures, specifically
      where wound healing and adhesion prevention are of clinical significance. This
      article reviews a bilateral case report experience of the novel utility of
      cryopreserved AM/UC tissue as an adhesion barrier and inflammatory modulator in
      conjunction with dorsal cheilectomy for treatment of hallux rigidus. 

PMID- 25396322
TI  - Use of Cryopreserved, Particulate Human Amniotic Membrane and Umbilical Cord
      (AM/UC) Tissue: A Case Series Study for Application in the Healing of Chronic
      Wounds.
AB  - Human amniotic membrane and umbilical cord tissues (AM/UC) are fetal tissues that
      contain proteins, cytokines, and growth factors that, when transplanted, can
      modulate inflammation and promote healing. Lyophilized, particulate AM/UC tissues
      can be used as wound coverings for chronic dermal ulcers or defects to promote
      granulation tissue formation and rapid re-epithelialization. This study reviews a
      case series of 5 patients presenting with chronic nonhealing wounds that received
      particulate AM/UC tissues (NEOX(r) FLO, Amniox Medical, Atlanta, GA). For all
      cases, wounds were debrided in the office setting and a single application of
      lyophilized particulate was used with minimal additional dressings. The
      lyophilized AM/UC tissue was placed within the wound bed and a dressing
      consisting of Adaptic(r), 2x2 or 4x4 (Systagenix, Quincy, MA), Kling(r) (Johnson
      & Johnson, New Brunswick, NJ), and ACETM (3M, St. Paul, MN) wrap were applied.
      Dressings were kept in place until weekly follow-up appointments in which a new
      Adaptic, 2x2 and Kling were applied. Overall, healing of wounds was noted to have
      a mean of 5 weeks to complete epithelialization. Upon complete healing patients
      were able to return to planned postoperative care and rehabilitation. Wound
      complications occur despite the best standard of care. Chronic wounds that remain
      weeks after surgery inhibit patients from progressing to physical rehabilitation
      and significantly affect patients both physically and mentally. These case
      presentations demonstrate how use of human AM/UC tissue may help wounds heal
      quickly and help patients return to normal function. 

PMID- 25396320
TI  - Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2
      Inhibitors) in clinical trials for cancer treatment.
AB  - Design of small-molecule inhibitors (MDM2 inhibitors) to block the MDM2-p53
      protein-protein interaction has been pursued as a new cancer therapeutic
      strategy. In recent years, potent, selective, and efficacious MDM2 inhibitors
      have been successfully obtained and seven such compounds have been advanced into
      early phase clinical trials for the treatment of human cancers. Here, we review
      the design, synthesis, properties, preclinical, and clinical studies of these
      clinical-stage MDM2 inhibitors. 

PMID- 25396323
TI  - The current status of biosynthetic mesh for ventral hernia repair.
AB  - Although synthetic mesh has dramatically reduced recurrence in elective hernia
      repair, its use in contaminated surgical fields has been traditionally associated
      with complications such as wound sepsis, enterocutaneous fistulas, and chronic
      prosthetic infection. Biologic meshes emerged in the late 1990s with a rapid
      popularity fueled largely by the demand for an appropriate substitute in lieu of
      synthetic mesh in these complex cases; however, the high cost and rate of hernia
      recurrence have tempered the initial enthusiasm. Biosynthetic meshes were
      developed as a possible cost-effective alternative to both synthetic and tissue
      derived products. Using biodegradable polymers instead of animal or cadaver
      tissue, they provide a temporary scaffold for deposition of proteins and cells
      necessary for tissue ingrowth, neovascularization, and host integration. Herein
      we review the current status of biosynthetic meshes for hernia repair. 

PMID- 25396324
TI  - An Open-label, Single-center, Retrospective Study of Cryopreserved Amniotic
      Membrane and Umbilical Cord Tissue as an Adjunct for Foot and Ankle Surgery.
AB  - The primary aim of this study was to compare preoperative assessments with
      postoperative outcomes from patients undergoing foot and ankle revisions and/or
      complex reconstructions with tendon and/or nerve involvement using cryopreserved
      human amniotic membrane and umbilical cord (cHAM/UC). We hypothesized complex
      foot and ankle surgery using amniotic membrane would be an effective treatment
      leading to reduced pain and improved functional outcomes. Fourteen patients (6
      male and 8 female) underwent open foot and ankle surgery during the study period.
      All 14 patients included in this cohort reported improvement, namely, lessened
      pain intensity both on the American Orthopedic Foot and Ankle Society (AOFAS)
      Ankle-Hindfoot Scale and the pain numeric rating scale (NRS), as well as improved
      functional status. The mean AOFAS score improved from 50 (range, 17-79)
      preoperatively to 85 (range, 67-100) postoperatively. The mean NRS score also
      improved from 8 (range, 4-10) preoperatively to 2 (range, 0-6) postoperatively
      with a mean percent change in pain NRS of 78% (range 17-100%). Both outcome
      scoring systems showed statistically significant differences (p < .0001) when we
      compared the preoperative and postoperative results. All patients included in the
      cohort showed improvement in both outcome measures. Further study of long-term
      endpoints is warranted. 

PMID- 25396325
TI  - Safety analysis of cryopreserved amniotic membrane/umbilical cord tissue in foot
      and ankle surgery: a consecutive case series of 124 patients.
AB  - Cryopreserved amnion tissues derived from amniotic membrane/umbilical cord
      (AM/UC) have been used extensively in ophthalmology for minimizing postoperative
      inflammation, pain, and adhesion formation following various surgical procedures.
      There is limited data in the current literature regarding the use of amnion
      tissue product in foot and ankle surgery. The purpose of this retrospective study
      is to report the short-term safety profile after in vivo application of
      cryopreserved AM/UC tissue use in foot and ankle surgery. A retrospective
      consecutive case series was performed for cases where amnion tissue was used with
      a minimum follow-up of 120 days between 2011 and 2012. The clinical outcomes of
      interest were postoperative infections, delayed or nonhealing wounds, adverse
      surgical site reactions, and repeat surgery for formal irrigation and
      debridement. One hundred twenty-four patients qualified for inclusion.
      Cryopreserved AM/UC tissue was introduced into the surgical wound and placed
      adjacent to the compromised and repaired tendons, most frequently in peroneal and
      Achilles tendon repairs. In this level IV consecutive case series cohort, there
      was an overall wound complication rate of 5.64%, with a re-operation rate of 1.6%
      (2/124). In each of these cases, patients had an irrigation and debridement with
      ultimate successful wound healing. The results of this study demonstrate that the
      use of amnion tissue in the foot and ankle setting is safe with a decreasing
      trend in overall complication rates compared with historically published norms. 

PMID- 25396326
TI  - Ex Vivo Expanded Allogeneic Mesenchymal Stem Cells With Bone Marrow
      Transplantation Improved Osteogenesis in Infants With Severe Hypophosphatasia.
AB  - Patients with severe hypophosphatasia (HPP) develop osteogenic impairment with
      extremely low alkaline phosphatase (ALP) activity, resulting in a fatal course
      during infancy. Mesenchymal stem cells (MSCs) differentiate into various
      mesenchymal lineages, including bone and cartilage. The efficacy of allogeneic
      hematopoietic stem cell transplantation for congenital skeletal and storage
      disorders is limited, and therefore we focused on MSCs for the treatment of HPP.
      To determine the effect of MSCs on osteogenesis, we performed multiple infusions
      of ex vivo expanded allogeneic MSCs for two patients with severe HPP who had
      undergone bone marrow transplantation (BMT) from asymptomatic relatives harboring
      the heterozygous mutation. There were improvements in not only bone
      mineralization but also muscle mass, respiratory function, and mental
      development, resulting in the patients being alive at the age of 3. After the
      infusion of MSCs, chimerism analysis of the mesenchymal cell fraction isolated
      from bone marrow in the patients demonstrated that donor-derived DNA sequences
      existed. Adverse events of BMT were tolerated, whereas those of MSC infusion did
      not occur. However, restoration of ALP activity was limited, and normal bony
      architecture could not be achieved. Our data suggest that multiple MSC infusions,
      following BMT, were effective and brought about clinical benefits for patients
      with lethal HPP. Allogeneic MSC-based therapy would be useful for patients with
      other congenital bone diseases and tissue disorders if the curative strategy to
      restore clinically normal features, including bony architecture, can be
      established. 

PMID- 25396327
TI  - High blood pressure in Panama: prevalence, sociodemographic and biologic profile,
      treatment, and control (STROBE).
AB  - The objective of this study is to estimate the prevalence, treatment, and control
      of high blood pressure, hypertension (HBP) in Panama and assess its associations
      with sociodemographic and biologic factors.A cross-sectional, descriptive study
      was conducted in Panama by administering a survey on cardiovascular risk factors
      to 3590 adults and measuring their blood pressure 3 times. A single-stage,
      probabilistic, and randomized sampling strategy with a multivariate
      stratification was used. The average blood pressure, confidence intervals (CIs),
      odds ratio (OR), and a value of P <= 0.05 were used for the analysis.The
      estimated prevalence of HBP was 29.6% (95% CI, 28.0-31.1); it was more prevalent
      in men than in women, OR = 1.37 (95% CI, 1.17-1.61); it increased with age and
      was more frequent among Afro-Panamanians (33.8%). HBP was associated with a
      family history of HBP with being physically inactive and a body mass index >=25.0
      kg/m or a waist circumference >90 cm in men and >88 cm in women (P < 0.001). Of
      those found to have HBP, 65.6% were aware of having HBP and taking medications,
      and of these, 47.2% had achieved control (<140/90 mm Hg).HBP is the most common
      cardiovascular risk factor among Panamanians and consequently an important public
      health problem in Panama. The health care system needs to give a high priority to
      HBP prevention programs and integrated care programs aimed at treating HBP,
      taking into consideration the changes in behavior that have been brought about by
      alterations in nutrition and sedentary lifestyles.

PMID- 25396328
TI  - Clinical and neuropsychological predictors of posttraumatic stress disorder.
AB  - Although acute responses to traumatic stress generally resolve within a few
      weeks, some individuals experience severe and persistent problems, such as
      posttraumatic stress disorder (PTSD). While studies have identified a variety of
      predictors of PTSD, not all data are consistent. This longitudinal study examined
      the predictive power of neurocognitive deficits with regard to PTSD severity.One
      hundred thirty one road traffic collision (RTC) survivors were included within 2
      weeks of the RTC and followed up 3 and 6 months later to determine severity of
      PTSD.Impairment on tests of information processing, executive functioning, verbal
      learning, and motor speed predicted PTSD severity when neuropsychological,
      clinical, and sociodemographic factors were all taken into account. Clinical
      variables (initial symptoms, psychiatric diagnoses, disability, trait anxiety,
      perceived stress, negative cognitions, and sleep) were associated with 3 and 6
      month PTSD severity, but only trait anxiety was predictive of PTSD severity.
      Ethnicity and education were also found to be predictive.These findings suggest
      implementation of a holistic approach to screening for PTSD and support a need
      for interventions that target neurocognitive, clinical, and social variables.
      Early targeted profiling of this group of trauma survivors can inform early
      clinical interventions and policy. 

PMID- 25396329
TI  - Multiparametric evaluation of breast lesions using PET-MRI: initial results and
      future perspectives.
AB  - The purpose of this study was to evaluate the diagnostic accuracy of
      multiparametric evaluation of breast lesions combining information of dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted
      imaging (DWI), and F-fluoro-deoxi-glucose (F-FDG) positron emission
      tomography/computed tomography (PET-CT). After approval of the institutional
      research ethics committee, 31 patients with suspicious breast lesions on MRI
      performed F-FDG PET-CT with a specific protocol for breast evaluation. Patients'
      mean age was 47.8 years (range, 29-77 years). Positron emission tomography and
      magnetic resonance imaging (PET-MRI) images were fused. A lesion was considered
      positive on multiparametric evaluation if at least 1 of the following was
      present: washout/type 3 kinetic curve on DCE-MRI, restricted diffusion on DWI
      with minimum apparent diffusion coefficient value <1.00 * 10 mm/s, and abnormal
      metabolism on F-FDG PET-CT (higher than the physiologic uptake of the normal
      breast parenchyma). Thirty-eight lesions with histologic correlation were
      evaluated on the 31 included patients, being 32 mass lesions (84.2%), and 6
      nonmass lesions (15.8%). Lesions' mean diameter was 31.1 mm (range, 8-94 mm).
      Multiparametric evaluation provided 100% sensitivity, 55.5% specificity, 87.9%
      positive predictive value, 100% negative predictive value, and 89.5% accuracy,
      with 29 true-positives results, 5 true-negatives, 4 false-positives, and no false
      negative results. Multiparametric evaluation with PET-MRI functional data showed
      good diagnostic accuracy to differentiate benign from malignant breast lesions,
      reducing the number of unnecessary biopsies, without missing any diagnosis of
      cancer in our case series.

PMID- 25396330
TI  - Clinical outcome of palliative radiotherapy for locally advanced symptomatic
      gastric cancer in the modern era.
AB  - The purpose of this study was to report the outcomes of patients with symptomatic
      locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using
      modern 3-dimensional conformal techniques.We retrospectively reviewed patients
      who had palliative RT for index symptoms of gastric bleeding, pain, and
      obstruction. Study endpoints included symptom response, median survival, and
      treatment toxicity.Of 115 patients with median age of 77 years, 78 (67.8%)
      patients had metastatic disease at the time of treatment. Index symptoms were
      gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients,
      respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40
      Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography
      (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain,
      and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17),
      respectively, and median duration of response was 99 days, 233 days, and 97 days,
      respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%.
      There was no difference in response rates between low (<=39 Gy) and high (>39 Gy)
      biologically effective dose (BED) regimens (alpha/beta ratio = 10). Median
      survival was significantly longer in patients who responded to RT compared with
      patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had
      grade 3 Common Toxicity Criteria equivalent toxicity
      (nausea/vomiting/anorexia).External beam RT delivered using 3-dimensional
      conformal techniques is highly effective and well tolerated in the local
      palliation of gastric cancer, with palliation lasting the majority of patient's
      lives. Short (<=39 Gy BED) RT schedules are adequate for effective symptom
      palliation. A phase II study of palliative gastric RT is ongoing.

PMID- 25396331
TI  - Toward patient-centered care: a systematic review of how to ask questions that
      matter to patients.
AB  - Clinicians rarely systematically document how their patients are feeling. Single
      item questions have been created to help obtain and monitor patient relevant
      outcomes, a requirement of patient-centered care.The objective of this review was
      to identify the psychometric properties for single items related to health
      aspects that only the patient can report (health perception, stress, pain,
      fatigue, depression, anxiety, and sleep quality). A secondary objective was to
      create a bank of valid single items in a format suitable for use in clinical
      practice.Data sources used were Ovid MEDLINE (1948 to May 2013), EMBASE (1960 to
      May 2013), and the Cumulative Index to Nursing and Allied Health Literature (1960
      to May 2013).For the study appraisal, 24 articles were systematically reviewed. A
      critical appraisal tool was used to determine the quality of articles.Items were
      included if they were tested as single items, related to the construct, measured
      symptom severity, and referred to recent experiences.The psychometric properties
      of each item were extracted. Validity and reliability was observed for the items
      when compared with clinical interviews or well-validated measures. The items for
      general health perception and anxiety showed weak to moderate strength
      correlations (r = 0.28-0.70). The depression and stress items showed good area
      under the receiver operating characteristic curve of 0.85 and 0.73-0.88,
      respectively, with high sensitivity and specificity. The fatigue item
      demonstrated a strong effect size and correlations up to r = 0.80. The 2 pain
      items and the sleep item showed high reliability (intraclass correlation
      coefficient [ICC] = 0.85, kappa = 0.76, ICC = 0.9, respectively).The search
      targeted articles about psychometric properties of single items. Articles that
      did not have this as the primary objective may have been missed. Furthermore, not
      all the articles included had the complete set of psychometric properties for
      each item.There is sufficient evidence to warrant the use of single items in
      clinical practice. They are simple, easily implemented, and efficient and thus
      provide an alternative to multi-item questionnaires. To facilitate their use, the
      top performing items were combined into the visual analog health states, which
      provides a quick profile of how the patient is feeling. This information would be
      useful for regular long-term monitoring.

PMID- 25396332
TI  - Radiofrequency ablation versus reresection in treating recurrent hepatocellular
      carcinoma: a meta-analysis.
AB  - Treatment for recurrent hepatocellular carcinoma (RHCC) remains controversial.
      This study tried to compare survival benefits between radiofrequency ablation
      (RFA) and reresection for RHCC patients following curative surgical
      treatments.Databases were searched for comparative studies published from 2008 to
      2014 on RFA versus reresection in treating RHCC. Meta-analysis was performed
      using a random or fixed-effect model to compare the overall survivals (OSs) and
      disease-free survivals (DFSs) between RFA and reresection. Begg funnel plot and
      Egger test were performed to assess the publication bias.Six retrospective
      comparative studies fulfilled our criteria and were included. For patients with
      RHCC, RFA was equivalent to reresection in 1-year OSs (odds ratio [OR] 0.86; 95%
      confidence interval [CI], 0.50-1.49; P = 0.587), 3-year OSs (OR 0.91; 95% CI,
      0.64-1.28; P = 0.581), and 5-year OSs (OR 0.97; 95% CI, 0.69-1.36; P = 0.846).
      However, reresection was superior to RFA in 3-year DFSs (OR 2.25; 95% CI, 1.37
      3.68; P = 0.001) and 5-year DFSs (OR 3.70; 95% CI, 1.98-6.93; P = 0.000). The
      outcome of 1-year DFSs was unstable with statistical heterogeneity among studies
      included in meta-analysis (I = 77.4%). No evidence of publication bias was found.
      RFA was considered as a less invasive modality for RHCC patients.RFA achieves
      comparable OSs as reresection in the treatment of RHCC, with lower postoperative
      complications.

PMID- 25396333
TI  - Increased serum levels of macrophage inflammatory protein-3alpha and cystatin a
      predict a poor prognosis of nasopharyngeal carcinoma.
AB  - This study was aimed to investigate the roles of serum macrophage inflammatory
      protein-3alpha (MIP-3alpha) and cystatin A in nasopharyngeal carcinoma (NPC)
      prognosis.The serum levels of MIP-3alpha and cystatin A in 140 primary NPC
      patients without distant metastasis were detected by enzyme-linked immunosorbent
      assay before and after treatment. The results were compared with those in 100
      healthy controls. The log-rank test was used to compare survival curves of the 2
      groups. Multivariate analysis of prognostic factors used Cox proportional hazards
      regression model.Serum levels of MIP-3alpha and cystatin A in pretreatment
      patients with NPC were higher than those in healthy controls. Concentrations of
      these 2 factors in the majority of patients after the therapy decreased to
      control level. Patients with high serum level of MIP-3alpha and cystatin A before
      treatment had poorer overall survival (OS), local recurrence-free survival, and
      distant metastasis-free survival than the ones with low level. In addition, serum
      pretreatment MIP-3alpha and cystatin A levels were independent prognostic factors
      for OS and distant metastasis-free survival of NPC patients; serum posttreatment
      MIP-3alpha and cystatin A levels were independent prognostic factors of local
      recurrence-free survival.Our results revealed that serum MIP-3alpha and cystatin
      A may be promising candidate prognostic factors for NPC, and higher serum levels
      of MIP-3alpha and cystatin A correlate with shorter probability of OS, local
      recurrence, and distant metastasis. 

PMID- 25396334
TI  - High-pitch coronary CT angiography at 70 kVp with low contrast medium volume:
      comparison of 80 and 100 kVp high-pitch protocols.
AB  - The purpose of this article is to evaluate image quality and radiation dose of
      prospectively electrocardiogram (ECG)-triggered high-pitch coronary computed
      tomography angiography (CCTA) at 70 kVp and 30 mL contrast medium.One hundred
      fifty patients with a heart rate <=70 beats per minute (bpm) underwent CCTA using
      a second-generation dual-source computed tomography (CT) scanner and were
      randomized into 3 groups according to tube voltage and contrast medium volume
      (370 mg/mL iodine concentration) (100 kVp group, 100 kVp/60 mL, n = 55; 80 kVp
      group, 80 kVp/60 mL, n = 44; 70 kVp group, 70 kVp/30 mL, n = 51). Objective and
      subjective image quality along with the effect of heart rate (HR) and body mass
      index (BMI) was evaluated and compared between the groups. Radiation dose was
      estimated for each patient.CT attenuation and image noise were higher in the 80
      and 70 kVp groups than in the 100 kVp group (all P < 0.001). Signal-to-noise
      ratios (SNRs) and contrast-to-noise ratios (CNRs) were lower in the 70 kVp group
      than in the 80 and 100 kVp groups (all P < 0.05). There was no difference for
      subjective image quality between the groups (P > 0.05). HR did not affect
      subjective image quality (all P > 0.05), while patients with BMI <23 kg/m had
      higher image quality than patients with BMI >=23 kg/m (P < 0.05). Compared with
      the 100 kVp group, the radiation dose of the 70 kVp group was reduced by 75%.In
      conclusion, prospectively ECG-triggered high-pitch 70 kVp/30 mL CCTA can obtain
      diagnostic image quality with lower radiation dose in selected patients with BMI
      <23 kg/m compared with 80/100 kVp/60 mL CCTA.

PMID- 25396336
TI  - Spontaneous resolution of Pneumocystis jirovecii pneumonia on high-resolution
      computed tomography in a patient with renal cell carcinoma.
AB  - BACKGROUND: Spontaneous resolution of Pneumocystis jirovecii pneumonia has rarely
      been reported. CASE REPORT: A 59-year-old man presented to our hospital because
      of pyrexia (38 degrees C) and shaking chills for 2 days. He had a history of
      right nephrectomy due to renal cell carcinoma and left upper lobectomy for lung
      metastasis in the last 1.5 years. Two months previously, he was treated with oral
      prednisolone (20 mg/day) plus the intravenous mTOR inhibitor, temsirolimus (25
      mg/week), for brain metastasis. On radiological examination, thoracic computed
      tomography showed diffuse ground glass opacities spreading in bilateral middle to
      lower lung fields. Although transbronchial biopsy specimens and bronchoalveolar
      lavage fluid demonstrated the presence of accumulation of black-colored
      Pneumocystis jirovecii cysts in the lung, his chief complaints and radiological
      abnormalities disappeared completely with no treatment. This case demonstrates a
      unique clinical presentation of Pneumocystis jirovecii pneumonia, in that
      spontaneous resolution was noted on clinical and sequential radiological
      evaluations. CONCLUSIONS: Increasing numbers of cytotoxic drugs and biological
      therapies have emerged, and changes in the immune status due to underlying
      diseases or administration of immunosuppressive drugs might affect the
      inflammatory process of Pneumocystis jirovecii pneumonia, as in the present case.

PMID- 25396335
TI  - Surgical treatment and clinical outcome of nonfunctional pancreatic
      neuroendocrine tumors: a 14-year experience from one single center.
AB  - Our primary aim of the present study was to analyze the clinical characteristics
      and surgical outcome of nonfunctional pancreatic neuroendocrine tumors (non-F-P
      NETs), with an emphasis on evaluating the prognostic value of the newly updated
      2010 grading classification of the World Health Organization (WHO).Data of 55
      consecutive patients who were surgically treated and pathologically diagnosed as
      non-F-P-NETs in our single institution from January 2000 to December 2013 were
      retrospectively collected.This entirety comprised of 55 patients (31 males and 24
      females), with a mean age of 51.24 +/- 12.95 years. Manifestations of non-F-P
      NETs were nonspecific. Distal pancreatectomy, pancreaticoduodenectomy, and local
      resection of pancreatic tumor were the most frequent surgical procedures, while
      pancreatic fistula was the most common but acceptable complication (30.3%). The
      overall 5-year survival rate of this entire cohort was 41.0%, with a median
      survival time of 60.4 months. Patients who underwent R0 resections obtained a
      better survival than those who did not (P < 0.005). As for the prognostic
      analysis, tumor size and lymph invasion were only statistically significant in
      univariate analysis (P = 0.046 and P < 0.05, respectively), whereas the newly
      updated 2010 grading classification of WHO (G1 and G2 vs G3), distant metastasis,
      and surgical margin were all meaningful in both univariate and multivariate
      analysis (P = 0.045, 0.001, and 0.042, respectively).Non-F-P-NETs are a kind of
      rare neoplasm, with mostly indolent malignancy. Patients with non-F-P-NETs could
      benefit from the radical resections. The new WHO criteria, distant metastasis and
      surgical margin, might be independent predictors for the prognosis of non-F-P
      NETs.

PMID- 25396337
TI  - Antinociceptive properties of physalins from Physalis angulata.
AB  - Pain is the most common reason a patient sees a physician. Nevertheless, the use
      of typical painkillers is not completely effective in controlling all pain
      syndromes; therefore further attempts have been made to develop improved
      analgesic drugs. The present study was undertaken to evaluate the antinociceptive
      properties of physalins B (1), D (2), F (3), and G (4) isolated from Physalis
      angulata in inflammatory and centrally mediated pain tests in mice. Systemic
      pretreatment with 1-4 produced dose-related antinociceptive effects on the
      writhing and formalin tests, traditional screening tools for the assessment of
      analgesic drugs. On the other hand, only 3 inhibited inflammatory parameters such
      as hyperalgesia, edema, and local production of TNF-alpha following induction
      with complete Freund's adjuvant. Treatment with 1, 3, and 4 produced an
      antinociceptive effect on the tail flick test, suggesting a centrally mediated
      antinociception. Reinforcing this idea, 2-4 enhanced the mice latency reaction
      time during the hot plate test. Mice treated with physalins did not demonstrate
      motor performance alterations. These results suggest that 1-4 present
      antinociceptive properties associated with central, but not anti-inflammatory,
      events and indicate a new pharmacological property of physalins. 

PMID- 25396338
TI  - Absence of significant structural changes near the magnetic ordering temperature
      in small-ion rare earth perovskite RMnO3.
AB  - Detailed structural measurements on multiple length scales were conducted on a
      new perovskite phase of ScMnO3, and on orthorhombic LuMnO3 as a benchmark.
      Complementary density functional theory (DFT) calculations were carried out, and
      predict that ScMnO3 possesses E-phase magnetic order at low temperature with
      displacements of the Mn sites (relative to the high temperature state) of ~0.07
      A, compared to ~0.04 A predicted for LuMnO3. However, detailed local,
      intermediate and long-range structural measurements by x-ray pair distribution
      function analysis, single crystal x-ray diffraction and x-ray absorption
      spectroscopy, find no local or long-range distortions on crossing into the low
      temperature E-phase of the magnetically ordered state. The measurements place
      upper limits on any structural changes to be at most one order of magnitude lower
      than DFT predictions and suggest that this theoretical approach does not properly
      account for the spin-lattice coupling in these oxides and may possibly predict
      the incorrect magnetic order at low temperatures. The results suggest that the
      electronic contribution to the electrical polarization dominates and should be
      more accurately treated in theoretical models.

PMID- 25396340
TI  - Ray D. Owen 1915-2014.

PMID- 25396339
TI  - What explains the intention to be physically active in cancer patients? Different
      determinants for active and insufficiently active patients.
AB  - In a qualitative elicitation study with 61 cancer patients, a broad range of
      attitudes toward physical activity could be obtained, especially negative
      attitudes among insufficiently active patients. Based on these results, a second
      quantitative study was conducted; 64 patients [40 men; 42% insufficiently active
      (<150 minutes/week)] completed a Theory of Planned Behavior (TPB) questionnaire.
      Regression analyses revealed that different variables of the TPB are relevant for
      explaining the intention to exercise for physically active (subjective norm) and
      insufficiently active (attitudes) cancer patients. Health professionals should
      adapt their support to the special needs of insufficiently active and active
      cancer patients. 

PMID- 25396341
TI  - The physician scientist: balancing clinical and research duties.
AB  - Physician scientists bridge the gap between biomedical research and clinical
      practice. However, the continuing decrease in number of people who choose this
      career path poses a threat to the advancement of biomedical science and the
      translation of research findings to clinical practice.

PMID- 25396342
TI  - Beyond the age of cellular discovery.
AB  - The combination of machine-learning tools and mass-cytometry measurements of more
      than 30 protein markers per cell comprehensively maps cell identity in the
      heterogeneous myeloid cell system and reveals the global effect of deletion of
      the gene encoding the receptor for the growth factor GM-CSF.

PMID- 25396343
TI  - Systematic analysis of immunodeficiency.
AB  - Humans deficient in the adaptor MyD88 or the kinase IRAK4 suffer from primary
      immunodeficiency. Blood cells from these patients show defective induction of
      specific subsets of genes after exposure to microbial stimuli in vitro.

PMID- 25396344
TI  - ParadYm shift: Ym1 and Ym2 as innate immunological regulators of IL-17.
AB  - Chitinase-like proteins are associated with type 2 immune responses and the
      'wound-healing' pathway, but their role has remained unclear. Studies have now
      highlighted their contribution to IL-17 production and their link to neutrophil
      activity required for the control of helminth infection.

PMID- 25396345
TI  - The RIP1-RIP3 complex initiates mitochondrial fission to fuel NLRP3.
AB  - Vesicular stomatitis virus, a single-stranded RNA virus, triggers activation of
      the serine-threonine kinases RIP1 and RIP3, which damages mitochondria by
      activating the GTPase DRP1. This results in excessive production of reactive
      oxygen species and subsequent activation of the NLRP3 inflammasome.

PMID- 25396354
TI  - Measurement-based quantum computation on two-body interacting qubits with
      adiabatic evolution.
AB  - A cluster state cannot be a unique ground state of a two-body interacting
      Hamiltonian. Here, we propose the creation of a cluster state of logical qubits
      encoded in spin-1/2 particles by adiabatically weakening two-body interactions.
      The proposal is valid for any spatial dimensional cluster states. Errors induced
      by thermal fluctuations and adiabatic evolution within finite time can be
      eliminated ensuring fault-tolerant quantum computing schemes. 

PMID- 25396353
TI  - Evaluating the efficacy of vilazodone in achieving remission in patients with
      major depressive disorder: post-hoc analyses of a phase IV trial.
AB  - The aim of this study was to evaluate the efficacy of vilazodone using different
      definitions of remission. Post-hoc analyses were carried out using data from an 8
      week, multicenter, randomized, double-blind, placebo-controlled trial of
      vilazodone 40 mg/day in adults with major depressive disorder (NCT01473394). The
      primary efficacy endpoint was a mean change in the Montgomery-Asberg Depression
      Rating Scale (MADRS) total score; additional measures included the Clinical
      Global Impressions-Severity (CGI-S) and Hamilton Rating Scale for Anxiety (HAMA)
      scores. In addition to treatment response (MADRS>=50% improvement), post-hoc
      analyses were carried out for remission of depressive symptoms [MADRS score<=10;
      MADRS<=5 (complete remission)], anxiety symptoms (HAMA<=7), and combined
      depression and anxiety symptoms (MADRS/HAMA<=10/<=7), as well as for overall
      symptom severity (CGI-S=1). Odds ratios (ORs) and numbers needed to treat (NNTs)
      were also calculated. Significant outcomes were obtained with vilazodone versus
      placebo for MADRS response (50.6 vs. 33.3%, OR=2.04, P<0.001, NNT=6), remission
      (34.0 vs. 21.8%, OR=1.82, P=0.003, NNT=9), and complete remission (18.2 vs. 8.3%,
      OR=2.42, P=0.002, NNT=11). More patients receiving vilazodone rather than placebo
      also met remission criteria for HAMA (48.8 vs. 35.2%, OR=1.82, P=0.002, NNT=8),
      MADRS/HAMA (32.1 vs. 20.4%, OR=1.83, P=0.004, NNT=9), and CGI-S (24.1 vs. 11.5%,
      OR=2.41, P<0.001, NNT=8). Treatment with vilazodone 40 mg/day may help adult
      patients with major depressive disorder achieve remission of depression and/or
      anxiety symptoms. 

PMID- 25396355
TI  - Dynamics of symmetry breaking during quantum real-time evolution in a minimal
      model system.
AB  - One necessary criterion for the thermalization of a nonequilibrium quantum many
      particle system is ergodicity. It is, however, not sufficient in cases where the
      asymptotic long-time state lies in a symmetry-broken phase but the initial state
      of nonequilibrium time evolution is fully symmetric with respect to this
      symmetry. In equilibrium, one particular symmetry-broken state is chosen as a
      result of an infinitesimal symmetry-breaking perturbation. From a dynamical point
      of view the question is: Can such an infinitesimal perturbation be sufficient for
      the system to establish a nonvanishing order during quantum real-time evolution?
      We study this question analytically for a minimal model system that can be
      associated with symmetry breaking, the ferromagnetic Kondo model. We show that
      after a quantum quench from a completely symmetric state the system is able to
      break its symmetry dynamically and discuss how these features can be observed
      experimentally. 

PMID- 25396356
TI  - Macroscopic response to microscopic intrinsic noise in three-dimensional Fisher
      fronts.
AB  - We study the dynamics of three-dimensional Fisher fronts in the presence of
      density fluctuations. To this end we simulate the Fisher equation subject to
      stochastic internal noise, and study how the front moves and roughens as a
      function of the number of particles in the system, N. Our results suggest that
      the macroscopic behavior of the system is driven by the microscopic dynamics at
      its leading edge where number fluctuations are dominated by rare events. Contrary
      to naive expectations, the strength of front fluctuations decays extremely slowly
      as 1/logN, inducing large-scale fluctuations which we find belong to the one
      dimensional Kardar-Parisi-Zhang universality class of kinetically rough
      interfaces. Hence, we find that there is no weak-noise regime for Fisher fronts,
      even for realistic numbers of particles in macroscopic systems. 

PMID- 25396352
TI  - Molecular regulation of effector and memory T cell differentiation.
AB  - Immunological memory is a cardinal feature of adaptive immunity and an important
      goal of vaccination strategies. Here we highlight advances in the understanding
      of the diverse T lymphocyte subsets that provide acute and long-term protection
      from infection. These include new insights into the transcription factors, and
      the upstream 'pioneering' factors that regulate their accessibility to key sites
      of gene regulation, as well as metabolic regulators that contribute to the
      differentiation of effector and memory subsets; ontogeny and defining
      characteristics of tissue-resident memory lymphocytes; and origins of the
      remarkable heterogeneity exhibited by activated T cells. Collectively, these
      findings underscore progress in delineating the underlying pathways that control
      diversification in T cell responses but also reveal gaps in the knowledge, as
      well as the challenges that arise in the application of this knowledge to
      rationally elicit desired T cell responses through vaccination and immunotherapy.

PMID- 25396357
TI  - Identification of a gravitational arrow of time.
AB  - It is widely believed that special initial conditions must be imposed on any time
      symmetric law if its solutions are to exhibit behavior of any kind that defines
      an "arrow of time." We show that this is not so. The simplest nontrivial time
      symmetric law that can be used to model a dynamically closed universe is the
      Newtonian N-body problem with vanishing total energy and angular momentum.
      Because of special properties of this system (likely to be shared by any law of
      the Universe), its typical solutions all divide at a uniquely defined point into
      two halves. In each, a well-defined measure of shape complexity fluctuates but
      grows irreversibly between rising bounds from that point. Structures that store
      dynamical information are created as the complexity grows and act as "records."
      Each solution can be viewed as having a single past and two distinct futures
      emerging from it. Any internal observer must be in one half of the solution and
      will only be aware of the records of one branch and deduce a unique past and
      future direction from inspection of the available records. 

PMID- 25396358
TI  - Indications of a late-time interaction in the dark sector.
AB  - We show that a general late-time interaction between cold dark matter and vacuum
      energy is favored by current cosmological data sets. We characterize the strength
      of the coupling by a dimensionless parameter q(V) that is free to take different
      values in four redshift bins from the primordial epoch up to today. This
      interacting scenario is in agreement with measurements of cosmic microwave
      background temperature anisotropies from the Planck satellite, supernovae Ia from
      Union 2.1 and redshift space distortions from a number of surveys, as well as
      with combinations of these different data sets. Our analysis of the 4-bin
      interaction shows that a nonzero interaction is likely at late times. We then
      focus on the case q(V)?0 in a single low-redshift bin, obtaining a nested one
      parameter extension of the standard LambdaCDM model. We study the Bayesian
      evidence, with respect to LambdaCDM, of this late-time interaction model, finding
      moderate evidence for an interaction starting at z=0.9, dependent upon the prior
      range chosen for the interaction strength parameter q(V). For this case the null
      interaction (q(V)=0, i.e., LambdaCDM) is excluded at 99% C.L.

PMID- 25396359
TI  - Particle-antiparticle asymmetries from annihilations.
AB  - An extensively studied mechanism to create particle-antiparticle asymmetries is
      the out-of-equilibrium and CP violating decay of a heavy particle. We, instead,
      examine how asymmetries can arise purely from 2->2 annihilations rather than from
      the usual 1->2 decays and inverse decays. We review the general conditions on the
      reaction rates that arise from S-matrix unitarity and CPT invariance, and show
      how these are implemented in the context of a simple toy model. We formulate the
      Boltzmann equations for this model, and present an example solution. 

PMID- 25396360
TI  - Resonances in coupled piK-etaK scattering from quantum chromodynamics.
AB  - Using a first-principles calculation within quantum chromodynamics, we are able
      to determine a pattern of strangeness=1 resonances that appear as complex
      singularities within coupled piK-etaK scattering amplitudes. We make use of
      numerical computation in the lattice discretized approach to the quantum field
      theory with light quark masses corresponding to m(pi)~400  MeV and at a single
      lattice spacing. The energy dependence of scattering amplitudes is extracted
      through their relationship to the discrete spectrum in a finite volume, which we
      map out in unprecedented detail.

PMID- 25396361
TI  - Approach to equilibrium in weakly coupled non-Abelian plasmas.
AB  - We follow the time evolution of non-Abelian gauge bosons from far-from
      equilibrium initial conditions to thermal equilibrium by numerically solving an
      effective kinetic equation that becomes accurate in the weak coupling limit. We
      consider isotropic initial conditions that are either highly overoccupied or
      underoccupied. We find that overoccupied systems thermalize through a self
      similar cascade reaching equilibrium in multiples of a thermalization time
      t(eq)~72./(1+0.12loglambda(-1))*1/lambda(2)T, whereas underoccupied systems
      undergo a "bottom-up" thermalization in a time
      t(eq)~[34.+21.log(Q/T)]/(1+0.037loglambda(-1))*(Q/T)(1/2)/lambda(2)T, where Q is
      the characteristic momentum scale of the initial condition. We apply this result
      to model initial stages of heavy-ion collisions and find rapid thermalization
      roughly in a time Qt(eq)?10 or t(eq)?1  fm/c.

PMID- 25396362
TI  - Lorentz invariance in chiral kinetic theory.
AB  - We show that Lorentz invariance is realized nontrivially in the classical action
      of a massless spin-1/2 particle with definite helicity. We find that the ordinary
      Lorentz transformation is modified by a shift orthogonal to the boost vector and
      the particle momentum. The shift ensures angular momentum conservation in
      particle collisions and implies a nonlocality of the collision term in the
      Lorentz-invariant kinetic theory due to side jumps. We show that 2/3 of the
      chiral-vortical effect for a uniformly rotating particle distribution can be
      attributed to the magnetic moment coupling required by the Lorentz invariance. We
      also show how the classical action can be obtained by taking the classical limit
      of the path integral for a Weyl particle. 

PMID- 25396363
TI  - Quadrupole transition strength in the (74)Ni nucleus and core polarization
      effects in the neutron-rich Ni isotopes.
AB  - The reduced transition probability B(E2;0(+)->2(+)) has been measured for the
      neutron-rich nucleus (74)Ni in an intermediate energy Coulomb excitation
      experiment performed at the National Superconducting Cyclotron Laboratory at
      Michigan State University. The obtained B(E2;0(+)->2(+))=642(-226)(+216)  e(2)
      fm(4) value defines a trend which is unexpectedly small if referred to (70)Ni and
      to a previous indirect determination of the transition strength in (74)Ni. This
      indicates a reduced polarization of the Z=28 core by the valence neutrons.
      Calculations in the pfgd model space reproduce well the experimental result
      indicating that the B(E2) strength predominantly corresponds to neutron
      excitations. The ratio of the neutron and proton multipole matrix elements
      supports such an interpretation.

PMID- 25396364
TI  - Interplay between quantum shells and orientation in quasifission.
AB  - The quasifission mechanism hinders fusion in heavy systems through breakup within
      zeptoseconds into two fragments with partial mass equilibration. Its dependence
      on the structure of both the collision partners and the final fragments is a key
      question. Our original approach is to combine an experimental measurement of the
      fragments' mass-angle correlations in (40)Ca+(238)U with microscopic quantum
      calculations. We demonstrate an unexpected interplay between the orientation of
      the prolate deformed (238)U with quantum shell effects in the fragments. In
      particular, calculations show that only collisions with the tip of (238)U produce
      quasifission fragments in the magic Z=82 region, while collisions with the side
      are the only ones that may result in fusion.

PMID- 25396365
TI  - Auxiliary-field quantum Monte Carlo simulations of neutron matter in chiral
      effective field theory.
AB  - We present variational Monte Carlo calculations of the neutron matter equation of
      state using chiral nuclear forces. The ground-state wave function of neutron
      matter, containing nonperturbative many-body correlations, is obtained from
      auxiliary-field quantum Monte Carlo simulations of up to about 340 neutrons
      interacting on a 10(3) discretized lattice. The evolution Hamiltonian is chosen
      to be attractive and spin independent in order to avoid the fermion sign problem
      and is constructed to best reproduce broad features of the chiral nuclear force.
      This is facilitated by choosing a lattice spacing of 1.5 fm, corresponding to a
      momentum-space cutoff of Lambda=414  MeV/c, a resolution scale at which strongly
      repulsive features of nuclear two-body forces are suppressed. Differences between
      the evolution potential and the full chiral nuclear interaction (Entem and
      Machleidt Lambda=414  MeV [L. Coraggio et al., Phys. Rev. C 87, 014322 (2013).

PMID- 25396366
TI  - Trapping cold ground state argon atoms.
AB  - We trap cold, ground state argon atoms in a deep optical dipole trap produced by
      a buildup cavity. The atoms, which are a general source for the sympathetic
      cooling of molecules, are loaded in the trap by quenching them from a cloud of
      laser-cooled metastable argon atoms. Although the ground state atoms cannot be
      directly probed, we detect them by observing the collisional loss of cotrapped
      metastable argon atoms and determine an elastic cross section. Using a type of
      parametric loss spectroscopy we also determine the polarizability of the
      metastable 4s[3/2](2) state to be (7.3+/-1.1)*10(-39)  C m(2)/V. Finally, Penning
      and associative losses of metastable atoms in the absence of light assisted
      collisions, are determined to be (3.3+/-0.8)*10(-10)  cm(3) s(-1).

PMID- 25396367
TI  - Exploring unconventional Hubbard models with doubly modulated lattice gases.
AB  - Recent experiments show that periodic modulations of cold atoms in optical
      lattices may be used to engineer and explore interesting models. We show that
      double modulation combining lattice shaking and modulated interactions allows for
      the engineering of a much broader class of lattice with correlated hopping, which
      we study for the particular case of one-dimensional systems. We show, in
      particular, that by using this double modulation it is possible to study Hubbard
      models with asymmetric hopping, which, contrary to the standard Hubbard model,
      present insulating phases with both parity and string order. Moreover, double
      modulation allows for the simulation of lattice models in unconventional
      parameter regimes, as we illustrate for the case of the spin-1/2 Fermi-Hubbard
      model with correlated hopping, a relevant model for cuprate superconductors. 

PMID- 25396368
TI  - Scattering of two photons from two distant qubits: exact solution.
AB  - We consider the inelastic scattering of two photons from two qubits separated by
      an arbitrary distance R and coupled to a one-dimensional transmission line. We
      present an exact, analytical solution to the problem, and use it to explore a
      particular configuration of qubits that is transparent to single-photon
      scattering, thus highlighting non-Markovian effects of inelastic two-photon
      scattering: strong two-photon interference and momentum dependent photon
      (anti)bunching. This latter effect can be seen as an inelastic generalization of
      the Hong-Ou-Mandel effect. 

PMID- 25396369
TI  - Interferometric measurement of the biphoton wave function.
AB  - Interference between an unknown two-photon state (a "biphoton") and the two
      photon component of a reference state gives a phase-sensitive arrival-time
      distribution containing full information about the biphoton temporal wave
      function. Using a coherent state as a reference, we observe this interference and
      reconstruct the wave function of single-mode biphotons from a low-intensity
      narrow band squeezed vacuum state. 

PMID- 25396370
TI  - Generalized radially self-accelerating helicon beams.
AB  - We report, in theory and experiment, on a new class of optical beams that are
      radially self-accelerating and nondiffracting. These beams continuously evolve on
      spiraling trajectories while maintaining their amplitude and phase distribution
      in their rotating rest frame. We provide a detailed insight into the theoretical
      origin and characteristics of radial self-acceleration and prove our findings
      experimentally. As radially self-accelerating beams are nonparaxial and a
      solution to the full scalar Helmholtz equation, they can be implemented in many
      linear wave systems beyond optics, from acoustic and elastic waves to surface
      waves in fluids and soft matter. Our work generalized the study of classical
      helicon beams to a complete set of solutions for rotating complex fields. 

PMID- 25396371
TI  - Weak ergodicity breaking and aging of chaotic transport in Hamiltonian systems.
AB  - Momentum diffusion is a widespread phenomenon in generic Hamiltonian systems. We
      show for the prototypical standard map that this implies weak ergodicity breaking
      for the superdiffusive transport in coordinate direction with an averaging
      dependent quadratic and cubic increase of the mean-squared displacement (MSD),
      respectively. This is explained via integrated Brownian motion, for which we
      derive aging time dependent expressions for the ensemble-averaged MSD, the
      distribution of time-averaged MSDs, and the ergodicity breaking parameter.
      Generalizations to other systems showing momentum diffusion are pointed out. 

PMID- 25396372
TI  - Turbulence reduces magnetic diffusivity in a liquid sodium experiment.
AB  - The contribution of small scale turbulent fluctuations to the induction of a mean
      magnetic field is investigated in our liquid sodium spherical Couette experiment
      with an imposed magnetic field. An inversion technique is applied to a large
      number of measurements at Rm~100 to obtain radial profiles of the alpha and beta
      effects and maps of the mean flow. It appears that the small scale turbulent
      fluctuations can be modeled as a strong contribution to the magnetic diffusivity
      that is negative in the interior region and positive close to the outer shell.
      Direct numerical simulations of our experiment support these results. The
      lowering of the effective magnetic diffusivity by small scale fluctuations
      implies that turbulence can actually help to achieve self-generation of large
      scale magnetic fields. 

PMID- 25396373
TI  - Ultrashort pulsed neutron source.
AB  - We report on a novel compact laser-driven neutron source with an unprecedented
      short pulse duration (<50  ps) and high peak flux (>10(18)  n/cm(2)/s), an order
      of magnitude higher than any existing source. In our experiments, high-energy
      electron jets are generated from thin (<3  MUm) plastic targets irradiated by a
      petawatt laser. These intense electron beams are employed to generate neutrons
      from a metal converter. Our method opens venues for enhancing neutron radiography
      contrast and for creating astrophysical conditions of heavy element synthesis in
      the laboratory.

PMID- 25396374
TI  - Femtosecond visualization of laser-induced optical relativistic electron
      microbunches.
AB  - It has long been known that lasers can interact with relativistic electrons in
      magnetic undulators to imprint sinusoidal modulations that can be used to slice
      electrons into microbunches equally separated at the laser wavelength. Here we
      report on the first direct measurement of laser-induced microbunching of a
      relativistic electron beam with femtosecond resolution in the time domain. Using
      a modified zero-phasing technique to map the electron beam's temporal structures
      into the energy space, we show that this method can be used to directly quantify
      the time and spectral content of coherent current modulations imprinted on the
      beam for harmonic and multicolor lasing applications in accelerator-based light
      sources. 

PMID- 25396375
TI  - Tunable mega-ampere electron current propagation in solids by dynamic control of
      lattice melt.
AB  - The influence of lattice-melt-induced resistivity gradients on the transport of
      mega-ampere currents of fast electrons in solids is investigated numerically and
      experimentally using laser-accelerated protons to induce isochoric heating.
      Tailoring the heating profile enables the resistive magnetic fields which
      strongly influence the current propagation to be manipulated. This tunable laser
      driven process enables important fast electron beam properties, including the
      beam divergence, profile, and symmetry to be actively tailored, and without
      recourse to complex target manufacture. 

PMID- 25396376
TI  - Nonlocal quantum fluctuations and fermionic superfluidity in the imbalanced
      attractive Hubbard model.
AB  - We study fermionic superfluidity in strongly anisotropic optical lattices with
      attractive interactions utilizing the cluster dynamical mean-field theory method,
      and focusing in particular on the role of nonlocal quantum fluctuations. We show
      that nonlocal quantum fluctuations impact the BCS superfluid transition
      dramatically. Moreover, we show that exotic superfluid states with a delicate
      order parameter structure, such as the Fulde-Ferrell-Larkin-Ovchinnikov phase
      driven by spin population imbalance, can emerge even in the presence of such
      strong fluctuations. 

PMID- 25396377
TI  - Stoner ferromagnetism in a thermal pseudospin-1/2 Bose gas.
AB  - We compute the finite-temperature phase diagram of a pseudospin-1/2 Bose gas with
      contact interactions, using two complementary methods: the random-phase
      approximation and self-consistent Hartree-Fock theory. We show that the spin
      dependent interactions, which break the (pseudo-) spin-rotational symmetry of the
      Hamiltonian, generally lead to the appearance of a magnetically ordered phase at
      temperatures above the superfluid transition. In three dimensions, we predict a
      normal easy-axis (easy-plane) ferromagnet for sufficiently strong repulsive
      (attractive) interspecies interactions, respectively. The normal easy-axis
      ferromagnet is the bosonic analog of Stoner ferromagnetism known in electronic
      systems. For the case of interspecies attraction, we also discuss the possibility
      of a bosonic analog of the Cooper-paired phase. This state is shown to
      significantly lose in energy to the transverse ferromagnet in three dimensions,
      but is more energetically competitive in lower dimensions. Extending our
      calculations to a spin-orbit-coupled Bose gas with equal Rashba and Dresselhaus
      type couplings (as recently realized in experiment), we investigate the
      possibility of stripe ordering in the normal phase. Within our approximations,
      however, we do not find an instability towards stripe formation, suggesting that
      the stripe order melts below the condensation temperature, which is consistent
      with the experimental observations of Ji et al. [Ji et al., Nat. Phys. 10, 314
      (2014)]. 

PMID- 25396378
TI  - Lattice anharmonicity and thermal conductivity from compressive sensing of first
      principles calculations.
AB  - First-principles prediction of lattice thermal conductivity kappa(L) of strongly
      anharmonic crystals is a long-standing challenge in solid-state physics. Making
      use of recent advances in information science, we propose a systematic and
      rigorous approach to this problem, compressive sensing lattice dynamics.
      Compressive sensing is used to select the physically important terms in the
      lattice dynamics model and determine their values in one shot. Nonintuitively,
      high accuracy is achieved when the model is trained on first-principles forces in
      quasirandom atomic configurations. The method is demonstrated for Si, NaCl, and
      Cu(12)Sb(4)S(13), an earth-abundant thermoelectric with strong phonon-phonon
      interactions that limit the room-temperature kappa(L) to values near the
      amorphous limit.

PMID- 25396379
TI  - Single molecular spectroscopy: identification of individual fullerene molecules.
AB  - We report the molecule-by-molecule spectroscopy of individual fullerenes by means
      of electron spectroscopy based on scanning transmission electron microscopy.
      Electron energy-loss fine structure analysis of carbon 1s absorption spectra is
      used to discriminate carbon allotropes with known symmetries. C(60) and C(70)
      molecules randomly stored inside carbon nanotubes are successfully identified at
      a single-molecular basis. We show that a single molecule impurity is detectable,
      allowing the recognition of an unexpected contaminant molecule with a different
      symmetry. Molecules inside carbon nanotubes thus preserve their intact molecular
      symmetry. In contrast, molecules anchored at or sandwiched between atomic BN
      layers show spectral modifications possibly due to a largely degraded structural
      symmetry. Moreover, by comparing the spectrum from a single C(60) molecule and
      its molecular crystal, we find hints of the influence of solid-state effects on
      its electronic structure.

PMID- 25396380
TI  - Local to extended transitions of resonant defect modes.
AB  - We study the localized modes created by introducing a resonant defect in a
      mechanical lattice. We find that modes introduced by resonant defects have
      profiles that can be tuned from being extremely localized to totally delocalized
      by an external force. This is in direct contrast with modes introduced by
      traditional mass or stiffness defects, in which the modes' profiles stay
      constant. We present an analytical model for resonant defects in one-dimensional
      nonlinear lattices, computationally demonstrate the equivalent effect in a two
      dimensional lattice, and experimentally observe the mode profiles in a granular
      crystal. While our study is concerned with nonlinear mechanical lattices, the
      generality of our model suggests that the same effect should be present in other
      types of periodic lattices. 

PMID- 25396381
TI  - Spatial coherence in near-field Raman scattering.
AB  - Inelastic light scattering in crystals has historically been treated as a
      spatially incoherent process, giving rise to incoherent optical radiation. Here
      we demonstrate that Raman scattering can be spatially coherent, in which case it
      depends on the dimensionality and symmetry of the scatterer. Using near-field
      spectroscopy, we measure a correlation length of ~30  nm for the optical phonons
      in graphene, the results varying with vibrational symmetries and spatial
      confinement of the phonons. 

PMID- 25396382
TI  - Intermolecular contrast in atomic force microscopy images without intermolecular
      bonds.
AB  - Intermolecular features in atomic force microscopy images of organic molecules
      have been ascribed to intermolecular bonds. A recent theoretical study [P. Hapala
      et al., Phys. Rev. B 90, 085421 (2014)] showed that these features can also be
      explained by the flexibility of molecule-terminated tips. We probe this effect by
      carrying out atomic force microscopy experiments on a model system that contains
      regions where intermolecular bonds should and should not exist between close-by
      molecules. Intermolecular features are observed in both regions, demonstrating
      that intermolecular contrast cannot be directly interpreted as intermolecular
      bonds.

PMID- 25396383
TI  - Density-functional prediction of a surface magnetic phase in SrTiO(3)/LaAlO(3)
      heterostructures induced by Al vacancies.
AB  - Based on first-principles density functional calculations we propose a novel Al
      vacancy induced ferromagnetism occurring at the LaAlO(3) surface of
      SrTiO(3)/LaAlO(3) bilayers. Magnetism at cation vacancies away from the surface
      is quenched due to charge compensation. Magnetic surface Al vacancies are
      stabilized due to the built-in electric field inside the LaAlO(3) region that
      raises the energy of the defect level, making charge compensation unfavorable.
      Surface Al vacancies prefer to form clusters and exhibit two-dimensional
      ferromagnetic alignment mediated by a long-range magnetic interaction. These
      results are discussed in light of recent experimental observations.

PMID- 25396384
TI  - Critical current oscillations in the intrinsic hybrid vortex state of
      SmFeAs(O,F).
AB  - In layered superconductors the order parameter may be modulated within the unit
      cell, leading to nontrivial modifications of the vortex core if the interlayer
      coherence length xi(c)(T) is comparable to the interlayer spacing. In the iron
      pnictide SmFeAs(O,F) (T(c)~50  K) this occurs below a crossover temperature
      T(?)~41  K, which separates two regimes of vortices: anisotropic Abrikosov-like
      at high and Josephson-like at low temperatures. Yet in the transition region
      around T(?), hybrid vortices between these two characteristics appear. Only in
      this region around T(?) and for magnetic fields well aligned with the FeAs
      layers, we observe oscillations of the c-axis critical current j(c)(H) periodic
      in 1/sqrt[H] due to a delicate balance of intervortex forces and interaction with
      the layered potential. j(c)(H) shows pronounced maxima when a hexagonal vortex
      lattice is commensurate with the underlying crystal structure. The narrow
      temperature window in which oscillations are observed suggests a significant
      suppression of the order parameter between the superconducting layers in
      SmFeAs(O,F), despite its low coherence length anisotropy (gamma(xi)~3-5).

PMID- 25396385
TI  - Transport in two-dimensional disordered semimetals.
AB  - We theoretically study transport in two-dimensional semimetals. Typically,
      electron and hole puddles emerge in the transport layer of these systems due to
      smooth fluctuations in the potential. We calculate the electric response of the
      electron-hole liquid subject to zero and finite perpendicular magnetic fields
      using an effective medium approximation and a complementary mapping on resistor
      networks. In the presence of smooth disorder and in the limit of a weak electron
      hole recombination rate, we find for small but finite overlap of the electron and
      hole bands an abrupt upturn in resistivity when lowering the temperature but no
      divergence at zero temperature. We discuss how this behavior is relevant for
      several experimental realizations and introduce a simple physical explanation for
      this effect. 

PMID- 25396386
TI  - Density of states in graphene with vacancies: midgap power law and frozen
      multifractality.
AB  - The density of states rho(E) of graphene is investigated numerically and within
      the self-consistent T-matrix approximation in the presence of vacancies within
      the tight binding model. The focus is on compensated disorder, where the
      concentration of vacancies n(A) and n(B) in both sublattices is the same.
      Formally, this model belongs to the chiral symmetry class BDI. The onlinear sigma
      model predicts for BDI a Gade-type singularity rho(E)~|E|(-1)exp[-|log(E)|(
      1/x)]. Our numerical data are comparable to this result in a preasymptotic regime
      that gives way, however, at even lower energies to rho(E)~E(-1)|log(E)|(-x),
      1<=x<2. We take this finding as evidence that, similar to the case of dirty d
      wave superconductors, generic bipartite random hopping models may also exhibit
      unconventional (strong-coupling) fixed points for certain kinds of randomly
      placed scatterers if these are strong enough. Our research suggests that graphene
      with (effective) vacancy disorder is a physical representative of such systems.

PMID- 25396387
TI  - Density of states in a two-dimensional chiral metal with vacancies.
AB  - We study quantum interference effects in a two-dimensional chiral metal
      (bipartite lattice) with vacancies. We demonstrate that randomly distributed
      vacancies constitute a peculiar type of chiral disorder leading to strong
      modifications of critical properties at zero energy as compared to those of
      conventional chiral metals. In particular, the average density of states diverges
      as rho?E(-1)|lnE|(-3/2) and the correlation length L(c)??[|lnE|] in the limit E
      >0. When the average density of vacancies is different in the two sublattices, a
      finite concentration of zero modes emerges and a gap in the quasiclassical
      density of states opens around zero energy. Interference effects smear this gap,
      resulting in exponentially small tails at low energies.

PMID- 25396388
TI  - Anisotropic dispersion and partial localization of acoustic surface plasmons on
      an atomically stepped surface: Au(788).
AB  - Understanding acoustic surface plasmons (ASPs) in the presence of nanosized
      gratings is necessary for the development of future devices that couple light
      with ASPs. We show here by experiment and theory that two ASPs exist on Au(788),
      a vicinal surface with an ordered array of monoatomic steps. The ASPs propagate
      across the steps as long as their wavelength exceeds the terrace width,
      thereafter becoming localized. Our investigation identifies, for the first time,
      ASPs coupled with intersubband transitions involving multiple surface-state
      subbands. 

PMID- 25396389
TI  - Angle-resolved photoemission spectroscopy of tetragonal CuO: evidence for
      intralayer coupling between cupratelike sublattices.
AB  - We investigate by angle-resolved photoemission the electronic structure of in
      situ grown tetragonal CuO, a synthetic quasi-two-dimensional edge-sharing
      cuprate. We show that, in spite of the very different nature of the copper oxide
      layers, with twice as many Cu in the CuO layers of tetragonal CuO as compared to
      the CuO(2) layers of the high-T(c) cuprates, the low-energy electronic
      excitations are surprisingly similar, with a Zhang-Rice singlet dispersing on
      weakly coupled cupratelike sublattices. This system should thus be considered as
      a member of the high-T(c) cuprate family, with, however, interesting differences
      due to the intralayer coupling between the cupratelike sublattices.

PMID- 25396390
TI  - Frequency comb generation in superconducting resonators.
AB  - We have generated frequency combs spanning 0.5 to 20 GHz in superconducting
      lambda/2 resonators at T=3  K. Thin films of niobium-titanium nitride enabled
      this development due to their low loss, high nonlinearity, low frequency
      dispersion, and high critical temperature. The combs nucleate as sidebands around
      multiples of the pump frequency. Selection rules for the allowed frequency
      emission are calculated using perturbation theory, and the measured spectrum is
      shown to agree with the theory. Sideband spacing is measured to be accurate to 1
      part in 10(8). The sidebands coalesce into a continuous comb structure observed
      to cover at least several frequency octaves.

PMID- 25396391
TI  - Raman scattering signatures of Kitaev spin liquids in A(2)IrO(3) iridates with
      A=Na or Li.
AB  - We show how Raman spectroscopy can serve as a valuable tool for diagnosing
      quantum spin liquids (QSL). We find that the Raman response of the gapless QSL of
      the Kitaev-Heisenberg model exhibits signatures of spin fractionalization into
      Majorana fermions, which give rise to a broad signal reflecting their density of
      states, and Z(2) gauge fluxes, which also contribute a sharp feature. We discuss
      the current experimental situation and explore more generally the effect of
      breaking the integrability on response functions of Kitaev spin liquids.

PMID- 25396392
TI  - Anomalous Hall effect in Weyl metals.
AB  - We present a theory of the anomalous Hall effect (AHE) in a doped Weyl semimetal,
      or Weyl metal, including both intrinsic and extrinsic (impurity scattering)
      contributions. We demonstrate that a Weyl metal is distinguished from an ordinary
      ferromagnetic metal by the absence of the extrinsic and the Fermi surface part of
      the intrinsic contributions to the AHE, as long as the Fermi energy is
      sufficiently close to the Weyl nodes. The AHE in a Weyl metal is thus shown to be
      a purely intrinsic, universal property, fully determined by the location of the
      Weyl nodes in the first Brillouin zone. 

PMID- 25396393
TI  - "Light-cone" dynamics after quantum quenches in spin chains.
AB  - Signal propagation in the nonequilibrium evolution after quantum quenches has
      recently attracted much experimental and theoretical interest. A key question
      arising in this context is what principles, and which of the properties of the
      quench, determine the characteristic propagation velocity. Here we investigate
      such issues for a class of quench protocols in one of the central paradigms of
      interacting many-particle quantum systems, the spin-1/2 Heisenberg XXZ chain. We
      consider quenches from a variety of initial thermal density matrices to the same
      final Hamiltonian using matrix product state methods. The spreading velocities
      are observed to vary substantially with the initial density matrix. However, we
      achieve a striking data collapse when the spreading velocity is considered to be
      a function of the excess energy. Using the fact that the XXZ chain is integrable,
      we present an explanation of the observed velocities in terms of "excitations" in
      an appropriately defined generalized Gibbs ensemble. 

PMID- 25396394
TI  - BaFe(2)Se(3) a high T(C) magnetic multiferroic with large ferrielectric
      polarization.
AB  - The iron selenides are important because of their superconducting properties.
      Here, an unexpected phenomenon is predicted to occur in an iron-selenide compound
      with a quasi-one-dimensional ladder geometry: BaFe(2)Se(3) should be a magnetic
      ferrielectric system, driven by its magnetic block order via exchange striction.
      A robust performance (high T(C) and large polarization) is expected. Different
      from most multiferroics, BaFe(2)Se(3) is ferrielectric, with a polarization that
      mostly cancels between ladders. However, its strong magnetostriction still
      produces a net polarization that is large (~0.1  MUC/cm(2)) as compared with most
      magnetic multiferroics. Its fully ferroelectric state, with energy only slightly
      higher than the ferrielectric, has a giant improper polarization ~2-3  MUC/cm(2).

PMID- 25396395
TI  - Two-dimensional analysis of the double-resonant 2D Raman mode in bilayer
      graphene.
AB  - By computing the double-resonant Raman scattering cross section completely from
      first principles and including the electron-electron interaction at the GW level,
      we unravel the dominant contributions for the double-resonant 2D mode in bilayer
      graphene. We show that, in contrast to previous works, the so-called inner
      processes are dominant and that the 2D-mode line shape is described by three
      dominant resonances around the K point. We show that the splitting of the
      transversal optical (TO) phonon branch in the Gamma-K direction, as large as 12 
      cm(-1) in the GW approximation, is of great importance for a thorough description
      of the 2D-mode line shape. Finally, we present a method to extract the TO phonon
      splitting and the splitting of the electronic bands from experimental data.

PMID- 25396396
TI  - Terasaki spiral ramps in the rough endoplasmic reticulum.
AB  - We present a model describing the morphology as well as the assembly of "Terasaki
      ramps," the recently discovered helicoidal connections linking adjacent sheets of
      the rough endoplasmic reticulum (ER). The fundamental unit is a localized
      symmetric double-ramped "parking garage" formed by two separated gently pitched,
      approximately helicoidal, ramps of opposite chiralities. This geometry is
      stabilized by a short-range repulsive interaction between ramps associated with
      bending energy which opposes the long-range attraction associated with tension.
      The ramp inner boundaries are themselves stabilized by the condensation of
      membrane-shaping proteins along their length. A mechanism for parking garage self
      assembly is proposed involving the nucleation of dipoles at the center of tubular
      three-way junctions within the smooth ER. Our predictions are compared with the
      experimental data. 

PMID- 25396397
TI  - Generalized master equation with non-Markovian multichromophoric Forster
      resonance energy transfer for modular exciton densities.
AB  - A generalized master equation (GME) governing quantum evolution of modular
      exciton density (MED) is derived for large scale light harvesting systems
      composed of weakly interacting modules of multiple chromophores. The GME-MED
      offers a practical framework to incorporate real time coherent quantum dynamics
      calculations of small length scales into dynamics over large length scales, and
      also provides a non-Markovian generalization and rigorous derivation of the Pauli
      master equation employing multichromophoric Forster resonance energy transfer
      rates. A test of the GME-MED for four sites of the Fenna-Matthews-Olson complex
      demonstrates how coherent dynamics of excitonic populations over coupled
      chromophores can be accurately described by transitions between subgroups
      (modules) of delocalized excitons. Application of the GME-MED to the exciton
      dynamics between a pair of light harvesting complexes in purple bacteria
      demonstrates its promise as a computationally efficient tool to investigate large
      scale exciton dynamics in complex environments. 

PMID- 25396398
TI  - Comment on "New limit on Lorentz-invariance- and CPT-violating neutron spin
      interactions using a free-spin-precession (3)He-(129)Xe comagnetometer".

PMID- 25396399
TI  - Allmendinger et al. reply:.

PMID- 25396400
TI  - Comment on "How to observe coherent electron dynamics directly".

PMID- 25396401
TI  - Suominen and Kirrander reply:.

PMID- 25396402
TI  - The HbA1c and all-cause mortality relationship in patients with type 2 diabetes
      is J-shaped: a meta-analysis of observational studies.
AB  - BACKGROUND: Low blood glucose and HbA1c levels are recommended in the literature
      on management of diabetes. However, data have shown that low blood glucose is
      associated with serious adverse effects for the patients and the recommendation
      has been criticized. Therefore, this article revisits the relationship between
      HbA1c and all-cause mortality by a meta-analysis of observational studies. AIM:
      The aim of this study is to determine whether there is a J- or U-shaped non
      linear relationship between HbA1c and all-cause mortality in type 2 diabetes
      patients, implying an increased risk to premature all-cause mortality at high and
      low levels of HbA1c. METHODS: A comprehensive literature search was conducted
      using PubMed, Medline, and Cochrane Library databases with strict
      inclusion/exclusion criteria. The published adjusted hazard ratios (HR) with 95%
      confidence intervals of all-cause mortality for each HbA1c category and per study
      were analyzed. Fractional polynomial regression was used with random effect
      modeling to assess the non-linear relationship of the HR trends between studies.
      Seven eligible observational studies with a total of 147,424 participants were
      included in the study. RESULTS: A significant J-shaped relationship was observed
      between HbA1c and all-cause mortality. Crude relative risk for all-cause
      mortality identified a decreased risk per 1% increase in HbA1c below 7.5% (58
      mmol/mol) (0.90, CI 0.86-0.94) and an increased risk per 1% increase in HbA1c
      above 7.5% (58 mmol/mol) (1.04, CI 1.01-1.06). Observational studies revealed a J
      shaped relationship between HbA1c and all-cause mortality, equivalent to an
      increased risk of mortality at high and low HbA1c levels. CONCLUSIONS: This
      increased mortality at high and low HbA1c levels has significant implications on
      investigating optimum clinical HbA1c targets as it suggests that there are upper
      and lower limits for creating a 'security zone' for diabetes management.

PMID- 25396403
TI  - Effects of dairy protein and fat on the metabolic syndrome and type 2 diabetes.
AB  - The incidence of the metabolic syndrome (MetS) and type 2 diabetes (T2D) is
      increasing worldwide. Evidence supports a negative relationship between the
      consumption of dairy products and risk of MetS and T2D. Dairy proteins are known
      to have a directly beneficial effect on hypertension, dyslipidemia, and
      hyperglycemia, but a detailed understanding of the underlying mechanisms is
      missing. It has been confirmed by observations that the insulinotropic effect of
      dairy proteins is associated with the amino acid composition; in particular
      branched-chain amino acids (BCAA) seem to be of vital importance. Dairy protein
      derived peptides may also contribute to the insulinotropic effect via dipeptidyl
      peptidase-4 (DPP-4) inhibitory activity, and may lower the blood pressure (BP).
      The lipid metabolism may be improved by whey protein (WP), which acts to reduce
      the postprandial triglyceride (TG) response. The effect of dairy fat is much more
      controversial because of the potentially harmful effect exerted by saturated
      fatty acid (SFA) on metabolic health. Recent observations suggest less adverse
      effects of SFA on metabolic health than previous assumed. However, little is
      known about dairy lipid fractions belonging to the groups of monounsaturated
      fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and phospholipids (PL).
      Dairy fat seems to act differently depending on the dairy product and the
      composition of macronutrients in the meal. Therefore, for a better understanding
      of the mechanisms behind the dairy protein and fat effect on MetS, we suggest
      that more human studies should be carried out to clarify the interactions of
      dairy protein and fat with macronutrients in the meal and other dairy components,
      such as micronutrients and microorganisms from fermented products. 

PMID- 25396404
TI  - The therapeutic potential of milk thistle in diabetes.
AB  - Milk thistle has been known for more than 2.000 years as a herbal remedy for a
      variety of disorders. It has mainly been used to treat liver and gallbladder
      diseases. Silibum marianum, the Latin term for the plant, and its seeds contain a
      whole family of natural compounds, called flavonolignans. Silimarin is a dry
      mixture of these compounds; it is extracted after processing with ethanol,
      methanol, and acetone. Silimarin contains mainly silibin A, silibin B, taxifolin,
      isosilibin A, isosilibin B, silichristin A, silidianin, and other compounds in
      smaller concentrations. Apart from its use in liver and gallbladder disorders,
      milk thistle has recently gained attention due to its hypoglycemic and
      hypolipidemic properties. Recently, a substance from milk thistle has been shown
      to possess peroxisome proliferator-activated receptor gamma (PPARgamma) agonist
      properties. PPARgamma is the molecular target of thiazolidinediones, which are
      used clinically as insulin sensitizers to lower blood glucose levels in diabetes
      type 2 patients. The thiazolidinedione type of PPARgamma ligands is an agonist
      with a very high binding affinity. However, this ligand type demonstrates a range
      of undesirable side effects, thus necessitating the search for new effective
      PPARgamma agonists. Interestingly, studies indicate that partial agonism of
      PPARgamma induces promising activity patterns by retaining the positive effects
      attributed to the full agonists, with reduced side effects. In this review, the
      therapeutic potential of milk thistle in the management of diabetes and its
      complications are discussed. 

PMID- 25396405
TI  - Microangiopathy is common in submucosal vessels of the colon in patients with
      diabetes mellitus.
AB  - OBJECTIVES: The pathophysiology behind gastrointestinal dysmotility in diabetes
      mellitus is unknown. Both esophageal dysmotility and gastroparesis have been
      shown to be associated with retinopathy, suggesting that microangiopathy is
      important in the common etiology. The aim of the present study was to examine
      whether patients with diabetes exhibit microangiopathy in the colon, and if
      present, to correlate microangiopathy with the clinical picture. METHODS:
      Consecutive patients subjected to colon surgery were identified in the
      southernmost districts of Skane between January 2011 and May 2013. Medical
      records were scrutinized, and patients with a history of diabetes were noted.
      Gender, age, type of diabetes, treatment, complications, and other concomitant
      diseases were registered. Histopathologic re-evaluation of surgical biopsies with
      morphometric analyses of submucosal vessels in the colon was performed.
      Morphometric examination and clinical data were compared with non-diabetic
      patients. RESULTS: Of 1135 identified patients during the time period studied, 95
      patients with diabetes were recognized and included. Fifty-three non-diabetic,
      randomly chosen patients served as controls. The mean age was 71.8 +/- 10.2 and
      71.4 +/- 9.5 years in diabetic and non-diabetic patients, respectively.
      Microangiopathy was found in 68.4% of diabetic patients and in 7.5% of non
      diabetic patients (p < 0.001). The wall-to-lumen ratio was 0.31 (0.23-0.46) in
      patients with diabetes compared with 0.16 (0.12-0.21) in non-diabetic patients (p
      < 0.001). No clinical association with microangiopathy could be verified.
      CONCLUSION: Microangiopathy in the colon is more common in diabetic than in non
      diabetic patients. The clinical significance of microangopathy has yet to be
      clarified.

PMID- 25396406
TI  - 10-year incidence of diabetes and associated risk factors in Greece: the ATTICA
      study (2002-2012).
AB  - BACKGROUND: The incidence of diabetes in the general population is increasing
      world-wide. The increase is attributed to the consumption of saturated fatty
      acids, obesity, lack of physical activity, genetic predisposition, and other
      factors, but knowledge about the reasons, biological mechanisms, and late
      complications is insufficient. It is therefore important to clarify the reasons
      more exactly through long-term clinical trials to stop the rise of diabetes and
      its complications. AIM: To evaluate the 10-year incidence of type 2 diabetes in
      apparently healthy Greek adults. METHODS: In 2001-2002, a random sample of 1514
      men (18-87 years old) and 1528 women (18-89 years old) was selected to
      participate in the ATTICA study. During 2011-2012, the 10-year follow-up was
      performed. Patients diagnosed with diabetes at baseline (n = 210) and those lost
      at the 10-year follow-up (n = 1347) were excluded, yielding a final sample of
      1485 participants. RESULTS: During the period of investigation, diabetes was
      diagnosed in 191 cases corresponding to a 12.9% incidence (95%CI: 10.4-15.4),
      with 13.4% (95%CI: 10.8-16) in men and 12.4% (95%CI: 10.1-14.7) in women. A
      relative increase was observed in the second half of the 10-year follow-up when
      age became significant. Multiple logistic regression analysis revealed that age
      (OR = 1.14, 95%CI: 1.09-1.19), abnormal waist-to-height ratio (OR = 3.27, 95%CI:
      1.07-10.0), fasting blood glucose (OR per 1 mg/dl = 0.05, 95%CI: 1.02-1.08),
      energy intake (OR per 500 kcal = 1.02, 95%CI: 1.01-1.35), and family history of
      diabetes (OR = 2.8, 95%CI: 1.30-6.03) were the most significant baseline
      predictors for diabetes, after adjusting for potential confounders. Waist-to
      height ratio showed the best explanatory power of all anthropometric variables.
      Physical activity exerts an effect on risk factors. Being active was found to
      eliminate the aggravating effect of diabetes family history and fasting blood
      glucose. CONCLUSIONS: The findings confirm the escalating increase of type 2
      diabetes incidence in Greece, which is in line with global trends. A lifestyle
      change in individuals at risk of developing diabetes towards healthier eating and
      increased physical activity would be an effective and inexpensive means of
      reducing diabetes.

PMID- 25396407
TI  - Effects of pistachio nut supplementation on blood glucose in patients with type 2
      diabetes: a randomized crossover trial.
AB  - BACKGROUND: Diabetes is a chronic, potentially debilitating, and often fatal
      disease. Dietary strategies to reduce postprandial glycemia are important in the
      prevention and treatment of diabetes. Nuts are rich in mono- and polyunsaturated
      fatty acids, which may reduce hyperglycemia and improve metabolism. OBJECTIVES:
      To evaluate the effectiveness of pistachio nut supplementation on glycemic and
      inflammatory measures in patients with type 2 diabetes. METHODS: In this double
      blind, randomized, placebo-controlled, crossover trial, 48 diabetic patients were
      equally assigned to groups A and B. Patients in group A received a snack of 25 g
      pistachio nuts twice a day for 12 weeks and group B received a control meal
      without nuts. After 12 weeks of intervention, the patients had an 8-week washout.
      Then the groups were displaced, and group B received the same amount of
      pistachios for 12 weeks. RESULTS: With respect to the total change in variables
      over both phases, there was a marked decrease in HbA1c (-0.4%) and fasting blood
      glucose (FBG) concentrations (-16 mg/dl) in the pistachio group compared with the
      control group (p <= 0.001 for both). There was no overall significant change in
      BMI, blood pressure, HOMA-IR, and C-reactive protein (CRP) concentrations.
      Analysis of the two phases separately showed a decrease in FBG by 14 mg/dl and in
      HbA1c by 0.45% in the treatment group (A) after 12 weeks, while no significant
      differences were seen in group B (control group). In the second phase, FBG
      decreased from 151.36 +/- 39.22 to 137.28 +/- 28.65 mg/dl (-14 mg/dl) and HbA1c
      decreased from 7.42 +/- 0.97 to 7.15 +/- 0.68 mg/dl (-0.28%, p = 0.013 and p =
      0.033, respectively) in the pistachio group (B). Pistachio consumption reduced
      systolic blood pressure (p = 0.007), BMI (p = 0.011), and CRP (p = 0.002) in
      patients from the treatment groups, but not insulin resistance. CONCLUSIONS:
      Dietary consumption of pistachio nuts as a snack has beneficial effects on
      glycemic control, blood pressure, obesity, and inflammation markers in diabetic
      patients.

PMID- 25396408
TI  - Comparative analysis of discrete exosome fractions obtained by differential
      centrifugation.
AB  - BACKGROUND: Cells release a mixture of extracellular vesicles, amongst these
      exosomes, that differ in size, density and composition. The standard isolation
      method for exosomes is centrifugation of fluid samples, typically at 100,000*g or
      above. Knowledge of the effect of discrete ultracentrifugation speeds on the
      purification from different cell types, however, is limited. METHODS: We examined
      the effect of applying differential centrifugation g-forces ranging from 33,000*g
      to 200,000*g on exosome yield and purity, using 2 unrelated human cell lines,
      embryonic kidney HEK293 cells and bladder carcinoma FL3 cells. The fractions were
      evaluated by nanoparticle tracking analysis (NTA), total protein quantification
      and immunoblotting for CD81, TSG101, syntenin, VDAC1 and calreticulin. RESULTS:
      NTA revealed the lowest background particle count in Dulbecco's Modified Eagle's
      Medium media devoid of phenol red and cleared by 200,000*g overnight
      centrifugation. The centrifugation tube fill level impacted the sedimentation
      efficacy. Comparative analysis by NTA, protein quantification, and detection of
      exosomal and contamination markers identified differences in vesicle size,
      concentration and composition of the obtained fractions. In addition, HEK293 and
      FL3 vesicles displayed marked differences in sedimentation characteristics.
      Exosomes were pelleted already at 33,000*g, a g-force which also removed most
      contaminating microsomes. Optimal vesicle-to-protein yield was obtained at
      67,000*g for HEK293 cells but 100,000*g for FL3 cells. Relative expression of
      exosomal markers (TSG101, CD81, syntenin) suggested presence of exosome
      subpopulations with variable sedimentation characteristics. CONCLUSIONS: Specific
      g-force/k factor usage during differential centrifugation greatly influences the
      purity and yield of exosomes. The vesicle sedimentation profile differed between
      the 2 cell lines.

PMID- 25396409
TI  - Low temperature activation of CO removal by O3-assisted catalysis.
AB  - Catalytic CO oxidation was activated at low temperature by injecting O3 as an
      additive. It was empirically confirmed that CO removal rate was dramatically
      enhanced by supplying a small amount of O3, and the reaction temperature was
      almost half that required for CO oxidation when using a catalyst only. By
      optimizing the concentration of O3, catalytic CO oxidation could be achieved
      within 1 min at low operational temperature. The removal rate of CO was sensitive
      to the concentration of O3, and a deduced reaction mechanism is discussed to
      explain how catalytic CO oxidation is activated but subsequently deactivated at
      higher O3 concentration. Moreover, the presence of C3H8 and C3H6 were considered
      to evaluate the effects of each gas on the enhancement of CO removal rate by O3.
      Finally, the rate of CO removal was evaluated with increasing O3 concentration
      for practical applications such as the cold-start problem in automobile engines. 

PMID- 25396410
TI  - Hydrologic landscape regionalisation using deductive classification and random
      forests.
AB  - Landscape classification and hydrological regionalisation studies are being
      increasingly used in ecohydrology to aid in the management and research of
      aquatic resources. We present a methodology for classifying hydrologic landscapes
      based on spatial environmental variables by employing non-parametric statistics
      and hybrid image classification. Our approach differed from previous
      classifications which have required the use of an a priori spatial unit (e.g. a
      catchment) which necessarily results in the loss of variability that is known to
      exist within those units. The use of a simple statistical approach to identify an
      appropriate number of classes eliminated the need for large amounts of post-hoc
      testing with different number of groups, or the selection and justification of an
      arbitrary number. Using statistical clustering, we identified 23 distinct groups
      within our training dataset. The use of a hybrid classification employing random
      forests extended this statistical clustering to an area of approximately 228,000
      km2 of south-eastern Australia without the need to rely on catchments, landscape
      units or stream sections. This extension resulted in a highly accurate
      regionalisation at both 30-m and 2.5-km resolution, and a less-accurate 10-km
      classification that would be more appropriate for use at a continental scale. A
      smaller case study, of an area covering 27,000 km2, demonstrated that the method
      preserved the intra- and inter-catchment variability that is known to exist in
      local hydrology, based on previous research. Preliminary analysis linking the
      regionalisation to streamflow indices is promising suggesting that the method
      could be used to predict streamflow behaviour in ungauged catchments. Our work
      therefore simplifies current classification frameworks that are becoming more
      popular in ecohydrology, while better retaining small-scale variability in
      hydrology, thus enabling future attempts to explain and visualise broad-scale
      hydrologic trends at the scale of catchments and continents. 

PMID- 25396411
TI  - Baseline MxA mRNA expression predicts interferon beta response in multiple
      sclerosis patients.
AB  - BACKGROUND: Myxovirus resistance protein A (MxA) is a molecule induced after
      interferon-beta injection, mostly used to evaluate its bioactivity. There is
      little available data on clinical utility of baseline MxA mRNA status. The
      objective of the study is to investigate whether baseline MxA mRNA expression can
      predict relapse and disease progression in multiple sclerosis patients treated
      with interferon-beta. METHODS: Baseline blood samples were obtained before the
      first interferon-beta dose was administered to evaluate MxA mRNA expression using
      real-time polymerase chain reaction (PCR). Demographic and clinical variables
      were prospectively recorded to define treatment responder and non responder
      groups. RESULTS: 104 patients were included in the study. Baseline MxA mRNA
      expression was significantly lower in the group of patients who met the
      definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of
      1.096 was established using Receiver Operating Characteristic analysis to
      differentiate between responders and non-responders (sensitivity 73.9%,
      specificity 69.0%). Survival analysis using this threshold showed that time to
      next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly
      higher in patients with lower MxA titers. CONCLUSION: The results suggest that
      baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis
      patients will respond or not to interferon-beta treatment.

PMID- 25396412
TI  - Impaired clearance of early apoptotic cells mediated by inhibitory IgG antibodies
      in patients with primary Sjogren's syndrome.
AB  - OBJECTIVES: Deficient efferocytosis (i.e. phagocytic clearance of apoptotic
      cells) has been frequently reported in systemic lupus erythematosus (SLE).
      Todate, patients with primary Sjogren's syndrome (SS) have not been assessed for
      phagocytosis of apoptotic cells (ApoCell-phagocytosis) and of particulate targets
      (microbeads, MB-phagocytosis). DESIGN: ApoCell-phagocytosis and MB-phagocytosis
      were comparatively assessed by flow cytometry in peripheral blood specimens and
      monocyte-derived macrophage (MDM) preparations from healthy blood donors (HBD)
      and consecutive SS, SLE and rheumatoid arthritis (RA) patients. Cross-admixture
      ApoCell-phagocytosis experiments were also performed using phagocytes from HBD or
      patients, and apoptotic cells pretreated with whole sera or purified serum IgG
      derived from patients or HBD. RESULTS: Compared to HBD, approximately half of SS
      and SLE patients studied (but not RA) manifested significantly reduced ApoCell
      phagocytosis (p<0.001) and MB-phagocytosis (p<0.003) by blood-borne phagocytes
      that correlated inversely with disease activity (p<=0.004). In cross-admixture
      assays, healthy monocytes showed significantly reduced ApoCell-phagocytosis when
      fed with apoptotic cells that were pretreated with sera or purified serum IgG
      preparations from SS and SLE patients (p<0.0001, compared to those from HBD or
      RA). Such aberrant effect of the SS and SLE sera and IgG preparations correlated
      linearly with their content of IgG antibodies against apoptotic cells
      (p<=0.0001). Phagocytic dysfunction maybe also present in certain SS and SLE
      patients, as supported by deficient capacity of MDM for ApoCell-phagocytosis and
      MB-phagocytosis under patients' serum-free conditions. CONCLUSION: Similarly to
      SLE, efferocytosis is frequently impaired in SS and is primarily due to the
      presence of inhibitory IgG anti-ApoCell antibodies and secondarily to phagocytes'
      dysfunction.

PMID- 25396413
TI  - Impact of early reoperation following living-donor liver transplantation on graft
      survival.
AB  - BACKGROUND: The reoperation rate remains high after liver transplantation and the
      impact of reoperation on graft and recipient outcome is unclear. The aim of our
      study is to evaluate the impact of early reoperation following living-donor liver
      transplantation (LDLT) on graft and recipient survival. METHODS: Recipients that
      underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007
      and December 2012 were divided into two groups, a reoperation group (n = 27) and
      a non-reoperation group (n = 84), and case-control study was conducted. RESULTS:
      Early reoperation was performed in 27 recipients (24.3%). Mean time [standard
      deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh
      class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative
      fresh frozen plasma administered were identified as possibly predictive
      variables, among which females and the amount of FFP were identified as
      independent risk factors for early reoperation by multivariable analysis. The 3-,
      and 6- month graft survival rates were 88.9% (95%confidential intervals [CI],
      70.7-96.4), and 85.2% (95%CI, 66.5-94.3), respectively, in the reoperation group
      (n = 27), and 95.2% (95%CI, 88.0-98.2), and 92.9% (95%CI, 85.0-96.8),
      respectively, in the non-reoperation group (n = 84) (the log-rank test, p =
      0.31). The 12- and 36- month overall survival rates were 96.3% (95%CI, 77.9
      99.5), and 88.3% (95%CI, 69.3-96.2), respectively, in the reoperation group, and
      89.3% (95%CI, 80.7-94.3) and 88.0% (95%CI, 79.2-93.4), respectively, in the non
      reoperation group (the log-rank test, p = 0.59). CONCLUSIONS: Observed graft
      survival for the recipients who underwent reoperation was lower compared to those
      who did not undergo reoperation, though the result was not significantly
      different. Recipient overall survival with reoperation was comparable to that
      without reoperation. The present findings enhance the importance of vigilant
      surveillance for postoperative complication and surgical rescue at an early
      postoperative stage in the LDLT setting.

PMID- 25396414
TI  - Correlation between renal function and common risk factors for chronic kidney
      disease in a healthy middle-aged population: a prospective observational 2-year
      study.
AB  - BACKGROUND/AIMS: Age, proteinuria, metabolic syndrome, and hyperuricemia are the
      reported risk factors for chronic kidney disease (CKD) and cardiovascular disease
      (CVD). However, the best predictor of changes in renal function in the early
      stages of renal disease in a healthy middle-aged population is still unknown. Our
      study evaluated the correlation between changes in renal function and common risk
      factors to determine such a predictor. METHODS: In total, 2,853 healthy persons
      aged <=50 years participated in the study. They had no proteinuria and were not
      on medications for hypertension, diabetes mellitus, hyperlipidemia, or
      hyperuricemia. Over 2 years, participants underwent annual health screening. The
      relationship between changes in estimated glomerular filtration rate (eGFR) and
      changes in risk factors for CKD was evaluated using univariate and multivariate
      linear regression analyses. RESULTS: Over 2 years, eGFR showed a significant
      decrease. Univariate regression analysis revealed that changes in fasting plasma
      glucose (FPG), total cholesterol, LDL-cholesterol, serum uric acid levels, and
      hemoglobin showed a significant negative correlation with changes in eGFR.
      Multiple regression analysis confirmed that changes in FPG, serum uric acid
      levels, in particular, and hemoglobin had a significant negative correlation with
      changes in eGFR. CONCLUSION: The changes in eGFR and other variables over 2 years
      were small and could be within expected biologic variation. A longer
      observational study is needed to elucidate whether FPG, serum uric acid and
      hemoglobin represent the earliest markers of eGFR decline.

PMID- 25396415
TI  - Gut microbial colonization orchestrates TLR2 expression, signaling and epithelial
      proliferation in the small intestinal mucosa.
AB  - The gut microbiota is an environmental factor that determines renewal of the
      intestinal epithelium and remodeling of the intestinal mucosa. At present, it is
      not resolved if components of the gut microbiota can augment innate immune
      sensing in the intestinal epithelium via the up-regulation of Toll-like receptors
      (TLRs). Here, we report that colonization of germ-free (GF) Swiss Webster mice
      with a complex gut microbiota augments expression of TLR2. The microbiota
      dependent up-regulation of components of the TLR2 signaling complex could be
      reversed by a 7 day broad-spectrum antibiotic treatment. TLR2 downstream
      signaling via the mitogen-activated protein kinase (ERK1/2) and protein-kinase B
      (AKT) induced by bacterial TLR2 agonists resulted in increased proliferation of
      the small intestinal epithelial cell line MODE-K. Mice that were colonized from
      birth with a normal gut microbiota (conventionally-raised; CONV-R) showed signs
      of increased small intestinal renewal and apoptosis compared with GF controls as
      indicated by elevated mRNA levels of the proliferation markers Ki67 and Cyclin
      D1, elevated transcripts of the apoptosis marker Caspase-3 and increased numbers
      of TUNEL-positive cells per intestinal villus structure. In accordance, TLR2
      deficient mice showed reduced proliferation and reduced apoptosis. Our findings
      suggest that a tuned proliferation response of epithelial cells following
      microbial colonization could aid to protect the host from its microbial
      colonizers and increase intestinal surface area. 

PMID- 25396416
TI  - Maximizing negative correlations in resting-state functional connectivity MRI by
      time-lag.
AB  - This paper aims to better understand the physiological meaning of negative
      correlations in resting state functional connectivity MRI (r-fcMRI). The
      correlations between anatomy-based brain regions of 18 healthy humans were
      calculated and analyzed with and without a correction for global signal and with
      and without spatial smoothing. In addition, correlations between anatomy-based
      brain regions of 18 naive anesthetized rats were calculated and compared to the
      human data. T-statistics were used to differentiate between positive and negative
      connections. The application of spatial smoothing and global signal correction
      increased the number of significant positive connections but their effect on
      negative connections was complex. Positive connections were mainly observed
      between cortical structures while most negative connections were observed between
      cortical and non-cortical structures with almost no negative connections between
      non-cortical structures. In both human and rats, negative connections were never
      observed between bilateral homologous regions. The main difference between
      positive and negative connections in both the human and rat data was that
      positive connections became less significant with time-lags, while negative
      connections became more significant with time-lag. This effect was evident in all
      four types of analyses (with and without global signal correction and spatial
      smoothing) but was most significant in the analysis with no correction for the
      global signal. We hypothesize that the valence of r-fcMRI connectivity reflects
      the relative contributions of cerebral blood volume (CBV) and flow (CBF) to the
      BOLD signal and that these relative contributions are location-specific. If
      cerebral circulation is primarily regulated by CBF in one region and by CBV in
      another, a functional connection between these regions can manifest as an r-fcMRI
      negative and time-delayed correlation. Similarly, negative correlations could
      result from spatially inhomogeneous responses of rCBV or rCBF alone.
      Consequently, neuronal regulation of brain circulation may be deduced from the
      valence of r-fcMRI connectivity. 

PMID- 25396417
TI  - Sporozoite immunization of human volunteers under mefloquine prophylaxis is safe,
      immunogenic and protective: a double-blind randomized controlled clinical trial.
AB  - Immunization of healthy volunteers with chloroquine ChemoProphylaxis and
      Sporozoites (CPS-CQ) efficiently and reproducibly induces dose-dependent and long
      lasting protection against homologous Plasmodium falciparum challenge. Here, we
      studied whether chloroquine can be replaced by mefloquine, which is the only
      other licensed anti-malarial chemoprophylactic drug that does not affect pre
      erythrocytic stages, exposure to which is considered essential for induction of
      protection by CPS immunization. In a double blind randomized controlled clinical
      trial, volunteers under either chloroquine prophylaxis (CPS-CQ, n = 5) or
      mefloquine prophylaxis (CPS-MQ, n = 10) received three sub-optimal CPS
      immunizations by bites from eight P. falciparum infected mosquitoes each, at
      monthly intervals. Four control volunteers received mefloquine prophylaxis and
      bites from uninfected mosquitoes. CPS-MQ immunization is safe and equally potent
      compared to CPS-CQ inducing protection in 7/10 (70%) versus 3/5 (60%) volunteers,
      respectively. Furthermore, specific antibody levels and cellular immune memory
      responses were comparable between both groups. We therefore conclude that
      mefloquine and chloroquine are equally effective in CPS-induced immune responses
      and protection. Trial registration: ClinicalTrials.gov NCT01422954.

PMID- 25396418
TI  - The aggregation of four reconstructed zygotes is the limit to improve the
      developmental competence of cloned equine embryos.
AB  - Embryo aggregation has been demonstrated to improve cloning efficiency in
      mammals. However, since no more than three embryos have been used for
      aggregation, the effect of using a larger number of cloned zygotes is unknown.
      Therefore, the goal of the present study was to determine whether increased
      numbers of cloned aggregated zygotes results in improved in vitro and in vivo
      embryo development in the equine. Zona-free reconstructed embryos (ZFRE's) were
      cultured in the well of the well system in four different experimental groups: I.
      1x, only one ZFRE per microwell; II. 3x, three per microwell; III. 4x, four per
      microwell; and IV. 5x, five ZFRE's per microwell. Embryo size was measured on day
      7, after which blastocysts from each experimental group were either a) maintained
      in culture from day 8 until day 16 to follow their growth rates, b) fixed to
      measure DNA fragmentation using the TUNEL assay, or c) transferred to
      synchronized mares. A higher blastocyst rate was observed on day 7 in the 4x
      group than in the 5x group. Non-aggregated embryos were smaller on day 8 compared
      to those aggregated, but from then on the in vitro growth was not different among
      experimental groups. Apoptotic cells averaged 10% of total cells of day 8
      blastocysts, independently of embryo aggregation. Only pregnancies resulting from
      the aggregation of up to four embryos per microwell went beyond the fifth month
      of gestation, and two of these pregnancies, derived from experimental groups 3x
      and 4x, resulted in live cloned foals. In summary, we showed that the in vitro
      and in vivo development of cloned zona-free embryos improved until the
      aggregation of four zygotes and declined when five reconstructed zygotes were
      aggregated. 

PMID- 25396419
TI  - Investigation of variants in UCP2 in Chinese type 2 diabetes and diabetic
      retinopathy.
AB  - PURPOSE: The aim of this study was to investigate variants in UCP2 genes in type
      2 diabetes mellitus (DM) and diabetic retinopathy (DR) in Chinese population.
      MATERIALS AND METHODS: We conducted a single nucleotide polymorphism-based and
      haplotype-based case-control study between the variants of UCP2 and DM and
      between the variants of UCP2 and DR in 479 Chinese patients with type 2 DM and
      479 control subjects without DM. Two SNPs (rs660339 and rs659366) were selected
      as genetic markers. RESULTS: The risk allele C at UCP2 rs660339 was closely
      associated with DM in Chinese population. There was significant difference in
      rs660339 between DM and controls (P = 0.0016; OR [95%CI]  = 1.37 (1.14-1.65)).
      Subjects who were homozygous of the C allele were more likely to develop DM. The
      frequency of C allele was higher in DM (58%) than in control (51%). But this
      locus didn't have a definite effect on the onset of non-proliferative diabetic
      retinopathy (NPDR) (P = 0.44; OR [95%CI]  = 0.80 (0.56-1.14)) and proliferative
      diabetic retinopathy (PDR) (P = 1.00; OR [95%CI]  = 0.99 (0.74-1.34)) comparing
      to subjects with DM without retinopathy (DWR), respectively. Moreover, the UCP2
      rs659366 polymorphism showed no significant difference between DM and control (P
      = 0.66; OR [95%CI]  = 1.10 (0.91-1.32)). However, there was a significant
      difference between PDR and DWR (P = 0.016; OR [95%CI]  = 0.66 (0.49-0.90)), but
      there was no difference between NPDR and DWR (P = 1.00; OR [95%CI]  = 0.96 (0.67
      1.37)). Participants who carried the G allele at rs659366 were more likely to
      develop PDR. For the haplotype, C-A was present more frequently in DM than in
      control (16% vs 7%), indicating that it was risky, and T-A was present less in DM
      than in control (29% vs 35%). Haplotype frequencies in DR and DWR showed no
      significant difference (P = 0.068). CONCLUSION: It was indicated that UCP2 may be
      implicated in the pathogenesis of type 2 DM and DR in Chinese population.

PMID- 25396420
TI  - Intranasal administration of human MSC for ischemic brain injury in the mouse: in
      vitro and in vivo neuroregenerative functions.
AB  - Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor
      and cognitive behavior in the neonatal hypoxic-ischemic (HI) mouse model. In this
      study, we investigated the potential of human MSCs (hMSCs) to treat HI brain
      injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is
      crucial for translation of our knowledge to the clinic. We determined the
      neuroregenerative potential of hMSCs in vitro and in vivo by intranasal
      administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups.
      1*10(6) or 2*10(6) hMSCs were administered intranasally 10 d post-HI. Motor
      behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of
      hMSCs to induce differentiation of mouse neural stem cell (mNSC) was determined
      using a transwell co-culture differentiation assay. To determine which
      chemotactic factors may play a role in mediating migration of MSCs to the lesion,
      we performed a PCR array on 84 chemotactic factors 10 days following sham
      operation, and at 10 and 17 days post-HI. Our results show that 2*10(6) hMSCs
      decrease lesion volume, improve motor behavior, and reduce scar formation and
      microglia activity. Moreover, we demonstrate that the differentiation assay
      reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs
      to differentiate into neurons in vitro. We also provide evidence that the
      chemotactic factor CXCL10 may play an important role in hMSC migration to the
      lesion site. This is suggested by our finding that CXCL10 is significantly
      upregulated at 10 days following HI, but not at 17 days after HI, a time when
      MSCs no longer reach the lesion when given intranasally. The results described in
      this work also tempt us to contemplate hMSCs not only as a potential treatment
      option for neonatal encephalopathy, but also for a plethora of degenerative and
      traumatic injuries of the nervous system.

PMID- 25396421
TI  - Protective role of the cholinergic anti-inflammatory pathway in a mouse model of
      viral myocarditis.
AB  - BACKGROUND: Activation of the cholinergic anti-inflammatory pathway, which relies
      on the alpha7nAchR (alpha 7 nicotinic acetylcholine receptor), has been shown to
      decrease proinflammatory cytokines. This relieves inflammatory responses and
      improves the prognosis of patients with experimental sepsis, endotoxemia,
      ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other
      inflammatory syndromes. However, whether the cholinergic anti-inflammatory
      pathway has an effect on acute viral myocarditis has not been investigated. Here,
      we studied the effects of the cholinergic anti-inflammatory pathway on acute
      viral myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: In a coxsackievirus B3 murine
      myocarditis model (Balb/c), nicotine and methyllycaconitine were used to
      stimulate and block the cholinergic anti-inflammatory pathway, respectively.
      Relevant signal pathways were studied to compare their effects on myocarditis,
      survival rate, histopathological changes, ultrastructural changes, and cytokine
      levels. Nicotine treatments significantly improved survival rate, attenuated
      myocardial lesions, and downregulated the expression of TNF-alpha and IL-6.
      Methyllycaconitine decreased survival rate, aggravated myocardial lesions, and
      upregulated the expression of TNF-alpha and IL-6. In addition, levels of the
      signaling protein phosphorylated STAT3 were higher in the nicotine group and
      lower in the methyllycaconitine group compared with the untreated myocarditis
      group. CONCLUSIONS/SIGNIFICANCE: These results show that nicotine protects mice
      from CVB3-induced viral myocarditis and that methyllycaconitine aggravates viral
      myocarditis in mice. Because nicotine is a alpha7nAchR agonist and
      methyllycaconitine is a alpha7nAchR antagonist, we conclude that alpha7nAchR
      activation increases the phosphorylation of STAT3, reduces the expression of TNF
      alpha and IL-6, and, ultimately, alleviates viral myocarditis. We also conclude
      that blocking alpha7nAchR reduces the phosphorylation of STAT3, increases the
      expression of TNF-alpha and IL-6, aggravating viral myocarditis.

PMID- 25396422
TI  - Short-term coral bleaching is not recorded by skeletal boron isotopes.
AB  - Coral skeletal boron isotopes have been established as a proxy for seawater pH,
      yet it remains unclear if and how this proxy is affected by seawater temperature.
      Specifically, it has never been directly tested whether coral bleaching caused by
      high water temperatures influences coral boron isotopes. Here we report the
      results from a controlled bleaching experiment conducted on the Caribbean corals
      Porites divaricata, Porites astreoides, and Orbicella faveolata. Stable boron
      (delta11B), carbon (delta13C), oxygen (delta18O) isotopes, Sr/Ca, Mg/Ca, U/Ca,
      and Ba/Ca ratios, as well as chlorophyll a concentrations and calcification rates
      were measured on coral skeletal material corresponding to the period during and
      immediately after the elevated temperature treatment and again after 6 weeks of
      recovery on the reef. We show that under these conditions, coral bleaching did
      not affect the boron isotopic signature in any coral species tested, despite
      significant changes in coral physiology. This contradicts published findings from
      coral cores, where significant decreases in boron isotopes were interpreted as
      corresponding to times of known mass bleaching events. In contrast, delta13C and
      delta18O exhibited major enrichment corresponding to decreases in calcification
      rates associated with bleaching. Sr/Ca of bleached corals did not consistently
      record the 1.2 degrees C difference in seawater temperature during the bleaching
      treatment, or alternatively show a consistent increase due to impaired
      photosynthesis and calcification. Mg/Ca, U/Ca, and Ba/Ca were affected by coral
      bleaching in some of the coral species, but the observed patterns could not be
      satisfactorily explained by temperature dependence or changes in coral
      physiology. This demonstrates that coral boron isotopes do not record short-term
      bleaching events, and therefore cannot be used as a proxy for past bleaching
      events. The robustness of coral boron isotopes to changes in coral physiology,
      however, suggests that reconstruction of seawater pH using boron isotopes should
      be uncompromised by short-term bleaching events. 

PMID- 25396423
TI  - Seed dormancy, seedling establishment and dynamics of the soil seed bank of Stipa
      bungeana (Poaceae) on the Loess Plateau of northwestern China.
AB  - Studying seed dormancy and its consequent effect can provide important
      information for vegetation restoration and management. The present study
      investigated seed dormancy, seedling emergence and seed survival in the soil seed
      bank of Stipa bungeana, a grass species used in restoration of degraded land on
      the Loess Plateau in northwest China. Dormancy of fresh seeds was determined by
      incubation of seeds over a range of temperatures in both light and dark. Seed
      germination was evaluated after mechanical removal of palea and lemma (hulls),
      chemical scarification and dry storage. Fresh and one-year-stored seeds were sown
      in the field, and seedling emergence was monitored weekly for 8 weeks.
      Furthermore, seeds were buried at different soil depths, and then retrieved every
      1 or 2 months to determine seed dormancy and seed viability in the laboratory.
      Fresh seeds (caryopses enclosed by palea and lemma) had non-deep physiological
      dormancy. Removal of palea and lemma, chemical scarification, dry storage
      (afterripening), gibberellin (GA3) and potassium nitrate (KNO3) significantly
      improved germination. Dormancy was completely released by removal of the hulls,
      but seeds on which hulls were put back to their original position germinated to
      only 46%. Pretreatment of seeds with a 30% NaOH solution for 60 min increased
      germination from 25% to 82%. Speed of seedling emergence from fresh seeds was
      significantly lower than that of seeds stored for 1 year. However, final
      percentage of seedling emergence did not differ significantly for seeds sown at
      depths of 0 and 1 cm. Most fresh seeds of S. bungeana buried in the field in
      early July either had germinated or lost viability by September. All seeds buried
      at a depth of 5 cm had lost viability after 5 months, whereas 12% and 4% seeds of
      those sown on the soil surface were viable after 5 and 12 months, respectively. 

PMID- 25396424
TI  - Mullerian mimicry as a result of codivergence between velvet ants and spider
      wasps.
AB  - Recent studies have delineated a large Nearctic Mullerian mimicry complex in
      Dasymutilla velvet ants. Psorthaspis spider wasps live in areas where this
      mimicry complex is found and are phenotypically similar to Dasymutilla. We tested
      the idea that Psorthaspis spider wasps are participating in the Dasymutilla
      mimicry complex and that they codiverged with Dasymutilla. We performed
      morphometric analyses and human perception tests, and tabulated distributional
      records to determine the fit of Psorthaspis to the Dasymutilla mimicry complex.
      We inferred a dated phylogeny using nuclear molecular markers (28S, elongation
      factor 1-alpha, long-wavelength rhodopsin and wingless) for Psorthaspis species
      and compared it to a dated phylogeny of Dasymutilla. We tested for codivergence
      between the two groups using two statistical analyses. Our results show that
      Psorthaspis spider wasps are morphologically similar to the Dasymutilla mimicry
      rings. In addition, our tests indicate that Psorthaspis and Dasymutilla
      codiverged to produce similar color patterns. This study expands the breadth of
      the Dasymutilla Mullerian mimicry complex and provides insights about how
      codivergence influenced the evolution of mimicry in these groups.

PMID- 25396425
TI  - Adhesive and migratory effects of phosphophoryn are modulated by flanking
      peptides of the integrin binding motif.
AB  - Phosphophoryn (PP) is generated from the proteolytic cleavage of dentin
      sialophosphoprotein (DSPP). Gene duplications in the ancestor dentin matrix
      protein-1 (DMP-1) genomic sequence created the DSPP gene in toothed animals. PP
      and DMP-1 are phosphorylated extracellular matrix proteins that belong to the
      family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Many
      SIBLING members have been shown to evoke various cell responses through the
      integrin-binding Arg-Gly-Asp (RGD) domain; however, the RGD-dependent function of
      PP is not yet fully understood. We demonstrated that recombinant PP did not
      exhibit any obvious cell adhesion ability, whereas the simultaneously purified
      recombinant DMP-1 did. A cell adhesion inhibitory analysis was performed by pre
      incubating human osteosarcoma MG63 cells with various PP peptides before seeding
      onto vitronectin. The results obtained revealed that the incorporation of more
      than one amino acid on both sides of the PP-RGD domain was unable to inhibit the
      adhesion of MG63 cells onto vitronectin. Furthermore, the inhibitory activity of
      a peptide containing the PP-RGD domain with an open carboxyl-terminal side (H
      463SDESDTNSESANESGSRGDA482-OH) was more potent than that of a peptide containing
      the RGD domain with an open amino-terminal side (H-478SRGDASYTSDESSDDDNDSDSH499
      OH). This phenomenon was supported by the potent cell adhesion and migration
      abilities of the recombinant truncated PP, which terminated with Ala482.
      Furthermore, various point mutations in Ala482 and/or Ser483 converted
      recombinant PP into cell-adhesive proteins. Therefore, we concluded that the
      Ala482-Ser483 flanking sequence, which was detected in primates and mice, was the
      key peptide bond that allowed the PP-RGD domain to be sequestered. The
      differential abilities of PP and DMP-1 to act on integrin imply that DSPP was
      duplicated from DMP-1 to serve as a crucial extracellular protein for tooth
      development rather than as an integrin-mediated signaling molecule. 

PMID- 25396426
TI  - Efficient immuno-modulation of TH1/TH2 biomarkers in 2,4-dinitrofluorobenzene
      induced atopic dermatitis: nanocarrier-mediated transcutaneous co-delivery of
      anti-inflammatory and antioxidant drugs.
AB  - The present study was conducted with the aim to investigate the immuno-modulatory
      and histological stabilization effects of nanocarrier-based transcutaneous co
      delivery of hydrocortisone (HC) and hydroxytyrosol (HT). In this investigation,
      the clinical and pharmacological efficacies of nanoparticle (NP)-based
      formulation to alleviate 2,4-dinitrofluorobenzene (DNFB)-induced atopic
      dermatitis (AD) was explored by using an NC/Nga mouse model. Ex vivo visual
      examination of AD induction in experimental mice indicated remarkable control of
      NP-based formulations in reducing pathological severity of AD-like skin lesions.
      Therapeutic effectiveness of NP-based formulations was also evaluated by
      comparing skin thickness of AD-induced NP-treated mice (456+/-27 um) with that of
      atopic mice (916+/-37 um). Analysis of the immuno-spectrum of AD also revealed
      the dominance of NP-based formulations in restraining immunoglobulin-E (IgE),
      histamine, prostaglandin-E2 (PGE2), vascular endothelial growth factor-alpha
      (VEGF-alpha), and T-helper cells (TH1/TH2) producing cytokines in serum and skin
      biopsies of tested mice. These anti-AD data were further supported by
      histological findings that revealed alleviated pathological features, including
      collagen fiber deposition, fibroblasts infiltration, and fragmentation of elastic
      fibers in experimental mice. Thus, NP-mediated transcutaneous co-delivery of HC
      and HT can be considered as a promising therapy for managing immunological and
      histological spectra associated with AD. 

PMID- 25396428
TI  - A well-circumscribed border with peripheral Doppler signal in sonographic image
      distinguishes epithelioid trophoblastic tumor from other gestational
      trophoblastic neoplasms.
AB  - As epithelioid trophoblastic tumor (ETT) shares similar clinical features with
      other gestational trophoblastic neoplasms (GTNs), it is likely to be clinically
      misdiagnosed and subsequently treated in an improper way. This study aimed to
      identify the sonographic features of ETT that are distinct from other GTNs,
      including placental site trophoblastic tumor (PSTT) and invasive
      mole/choriocarcinoma (IM/CC). Here, we retrospectively analyzed ultrasound images
      of 12 patients with ETT in comparison with those of 21 patients with PSTT and 24
      patients with IM/CC. The results showed that maximal diameter and hemodynamic
      parameters were not significantly different among ETT, PSTT and IM/CC (P>0.05).
      However, a well-circumscribed border with hypoechogenic halo was identified in
      the gray-scale sonogram in all 12 cases of ETT, while only in 1 out of 21 cases
      of PSTT and 1 out of 16 cases of IM/CC (P<0.001 for ETT vs. PSTT or IM/CC).
      Moreover, a peripheral pattern of Doppler signals was observed in 11 out of 12
      ETT lesions, showing relatively more Doppler signal spots around the tumor border
      than within the boundary, while a non-peripheral pattern of Doppler signals in
      all 21 PSTT cases and 14 out of 16 IM/CC cases: with minimal, moderate or
      remarkable signal spots within the tumor, but not along the tumor (P<0.001 for
      ETT vs. PSTT or IM/CC). These distinct sonographic features of ETT correlated
      with histopathologic observations, such as expansive growth pattern and vascular
      morphology. Thus, we draw the conclusions that the well-circumscribed border with
      peripheral Doppler signal may serve as a reliable sonographic feature to
      discriminate ETT from other types of GTNs. With further validation in a larger
      patient set in our ongoing multi-center study, this finding will be potentially
      developed into a non-invasive pre-operative GTN subtyping method for ETT. 

PMID- 25396429
TI  - Ligand binding reveals a role for heme in translationally-controlled tumor
      protein dimerization.
AB  - The translationally-controlled tumor protein (TCTP) is a highly conserved,
      ubiquitously expressed, abundant protein that is broadly distributed among
      eukaryotes. Its biological function spans numerous cellular processes ranging
      from regulation of the cell cycle and microtubule stabilization to cell growth,
      transformation, and death processes. In this work, we propose a new function for
      TCTP as a "buffer protein" controlling cellular homeostasis. We demonstrate that
      binding of hemin to TCTP is mediated by a conserved His-containing motif
      (His76His77) followed by dimerization, an event that involves ligand-mediated
      conformational changes and that is necessary to trigger TCTP's cytokine-like
      activity. Mutation in both His residues to Ala prevents hemin from binding and
      abrogates oligomerization, suggesting that the ligand site localizes at the
      interface of the oligomer. Unlike heme, binding of Ca2+ ligand to TCTP does not
      alter its monomeric state; although, Ca2+ is able to destabilize an existing TCTP
      dimer created by hemin addition. In agreement with TCTP's proposed buffer
      function, ligand binding occurs at high concentration, allowing the "buffer"
      condition to be dissociated from TCTP's role as a component of signal
      transduction mechanisms. 

PMID- 25396430
TI  - Silver wire amplifies the signaling mechanism for IL-1beta production more than
      silver submicroparticles in human monocytic THP-1 cells.
AB  - Silver materials have been widely used in diverse fields. However, their toxicity
      and their mechanism, especially in different forms, have not been studied
      sufficiently. Thus, cytotoxicity, apoptosis, and interleukin-1beta (IL-1beta)
      production were investigated using macrophage-like THP-1 cells in the presence of
      Ag microparticles (AgMPs, 2.7 um), Ag submicroparticles (AgSMPs, 150 nm), and Ag
      wires (AgWs, 274 nm*5.3 um). The levels of cytotoxicity, apoptosis, and IL-1beta
      production by AgWs were higher than those by the other two AgSMPs and AgMPs. This
      trend was also observed with each step of the signaling mechanism for IL-1beta
      production, which is a single pathway affiliated with ROS generation or lysosomal
      rupture or both, cathepsin B, caspase-1 (NALP3 inflammasome), and finally IL
      1beta production in THP-1 cells. All these results suggest that, for development
      of safe and effective silver materials, the shape or form of silver materials
      should be considered, especially for macrophage cell lines because epithelial
      cell lines are not overly sensitive to silver materials. 

PMID- 25396431
TI  - Beadex function in the motor neurons is essential for female reproduction in
      Drosophila melanogaster.
AB  - Drosophila melanogaster has served as an excellent model system for understanding
      the neuronal circuits and molecular mechanisms regulating complex behaviors. The
      Drosophila female reproductive circuits, in particular, are well studied and can
      be used as a tool to understand the role of novel genes in neuronal function in
      general and female reproduction in particular. In the present study, the role of
      Beadex, a transcription co-activator, in Drosophila female reproduction was
      assessed by generation of mutant and knock down studies. Null allele of Beadex
      was generated by transposase induced excision of P-element present within an
      intron of Beadex gene. The mutant showed highly compromised reproductive
      abilities as evaluated by reduced fecundity and fertility, abnormal oviposition
      and more importantly, the failure of sperm release from storage organs. However,
      no defect was found in the overall ovariole development. Tissue specific,
      targeted knock down of Beadex indicated that its function in neurons is important
      for efficient female reproduction, since its neuronal knock down led to
      compromised female reproductive abilities, similar to Beadex null females.
      Further, different neuronal class specific knock down studies revealed that
      Beadex function is required in motor neurons for normal fecundity and fertility
      of females. Thus, the present study attributes a novel and essential role for
      Beadex in female reproduction through neurons. 

PMID- 25396452
TI  - The Expressive and the Receptive One Word Picture Vocabulary test (EOWPVT &
      ROWPVT). (A combine pilot study and validation of the tests' in normal Greek
      population - aged from 18 years till 18 years and 11 months).

PMID- 25396486
TI  - Results of five years study of the epidemiological characteristics of psychotic
      patients participated in the program of Day hospital, in the Hellenic Center for
      Mental Health and Research, Branch of Heraklion, Crete.

PMID- 25396672
TI  - "One-stop shop" for medicare reimbursement information.

PMID- 25396673
TI  - Healing process in mice model of surgical wounds enhanced by Phyllocaulis
      boraceiensis mucus.
AB  - OBJECTIVES: Phyllocaulis boraceiensis mucus has been studied as a potential
      source of new natural compounds that are capable of inducing proliferation and
      remodeling tissue. The aim of this study was to evaluate the clinical aspects of
      healing in the wounded mouse skin, which was treated with an ointment that was
      composed of mucus, which was released by P boraceiensis. MATERIALS & METHODS:
      Mice were submitted to a 1-cm dorsal excision. The control group (T1) was treated
      with papain; the T2 group was treated with papain that was associated with 0.18
      MUg/MUL of mucus; and the T3 group was treated with papain that was associated
      with 0.012 MUg/MUL of mucus. RESULTS: Accelerated proliferation was observed
      after 3 days in the T3 group, presenting a high deposition of fibroblasts at the
      wound margin, whereas accelerated proliferation in the T1 group began 5 days
      after surgery. The T2 group presented inflammation during all periods of
      observation, and even when healing had already begun, the new tissue showed
      capillary fragility. Remodeling began after 4 days in the T3 group, whereas
      remodeling began after 6 days in the other groups. T3 showed edema, hyperemia,
      and bleeding only until the fifth day, and granulation and scar tissues intensely
      appeared from the 11th day forward. T1 and T2 groups exhibited edema, hyperemia,
      and bleeding until the 11th day, and granulation and scar tissues appeared after
      the 13th day. CONCLUSION: The healing process and wound closure were efficient
      after the daily application of 0.012 MUg/MUL P boraceiensis mucus.

PMID- 25396674
TI  - A randomized, double-blind, comparative study to assess the safety and efficacy
      of topical retapamulin ointment 1% versus oral linezolid in the treatment of
      secondarily infected traumatic lesions and impetigo due to methicillin-resistant
      Staphylococcus aureus.
AB  - OBJECTIVE: To evaluate the clinical and bacteriological efficacy of topical
      retapamulin ointment 1% versus oral linezolid in the treatment of patients with
      secondarily infected traumatic lesions (SITLs; excluding abscesses) or impetigo
      due to methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: A randomized,
      double-blind, double-dummy, multicenter, comparative study (NCT00852540).
      SETTING: Patients recruited from 36 study centers in the United States. PATIENTS:
      Patients 2 months or older with SITL (including secondarily infected lacerations
      or sutured wounds) or impetigo (bullous and nonbullous) suitable for treatment
      with a topical antibiotic, with a total Skin Infection Rating Scale score of 8 or
      greater, including a pus/exudate score of 3 or greater. INTERVENTIONS: Patients
      received retapamulin ointment 1% (plus oral placebo), twice daily for 5 days or
      oral linezolid (plus placebo ointment) 2 or 3 times daily for 10 days. MAIN
      OUTCOME MEASURE: Primary end point: clinical response (success/failure) at follow
      up in patients with MRSA at baseline (per-protocol population). Secondary
      efficacy end points: clinical and microbiologic response and outcome at follow-up
      and end of therapy; therapeutic response at follow-up. MAIN RESULTS: The majority
      of patients had SITL (70.4% [188/267] and 66.4% [91/137] in the retapamulin and
      linezolid groups, respectively; intent-to-treat clinical population). Clinical
      success rate at follow-up was significantly lower in the retapamulin versus the
      linezolid group (63.9% [39/61] vs 90.6% [29/32], respectively; difference in
      success rate -26.7%; 95% CI, -45.7 to -7.7). CONCLUSIONS: Clinical success rate
      at follow-up in the per-protocol MRSA population was significantly lower in the
      retapamulin versus the linezolid group. It could not be determined whether this
      was related to study design, bacterial virulence, or retapamulin activity.

PMID- 25396675
TI  - Measure it: proper wheelchair fit is key to ensuring function while protecting
      skin integrity.
AB  - The objectives of this article are to help the clinician to better recognize the
      basic biomechanics of posture, describe the appropriate means to configure a
      wheelchair to permit proper postural support, and to identify common problems
      arising from improper wheelchair fit.

PMID- 25396677
TI  - The value of smart workflows in a specialty electronic medical record.

PMID- 25396678
TI  - Germanium oxide removal by citric acid and thiol passivation from citric acid
      terminated Ge(100).
AB  - Many applications of germanium (Ge) are underpinned by effective oxide removal
      and surface passivation. This important surface treatment step often requires H-X
      (X = Cl, Br, I) or HF etchants. Here, we show that aqueous citric acid solutions
      are effective in the removal of GeOx. The stability of citric acid-treated
      Ge(100) is compared to HF and HCl treated surfaces and analyzed by X-ray
      photoelectron spectroscopy. Further Ge surface passivation was investigated by
      thiolation using alkane monothiols and dithiols. The organic passivation layers
      show good stability with no oxide regrowth observed after 3 days of ambient
      exposure. 

PMID- 25396679
TI  - Validation of a molecular and pathological model for five-year mortality risk in
      patients with early stage lung adenocarcinoma.
AB  - INTRODUCTION: The aim of this study was to validate a molecular expression
      signature [cell cycle progression (CCP) score] that identifies patients with a
      higher risk of cancer-related death after surgical resection of early stage (I
      II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness
      of combining CCP score and pathological stage for predicting lung cancer
      mortality. METHODS: Formalin-fixed paraffin-embedded surgical tumor samples from
      650 patients diagnosed with stage I and II adenocarcinoma who underwent
      definitive surgical treatment without adjuvant chemotherapy were analyzed for 31
      proliferation genes by quantitative real-time polymerase chain reaction. The
      prognostic discrimination of the expression score was assessed by Cox
      proportional hazards analysis using 5-year lung cancer-specific death as primary
      outcome. RESULTS: The CCP score was a significant predictor of lung cancer
      specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per
      interquartile range (95% confidence interval = 1.12-1.90; p = 0.0050)]. The
      prognostic score, a combination of CCP score and pathological stage, was a more
      significant indicator of lung cancer mortality risk than pathological stage in
      the full cohort (HR = 2.01; p = 2.8 * 10) and in stage I patients (HR = 1.67; p =
      0.00027). Using the 85th percentile of the prognostic score as a threshold, there
      was a significant difference in lung cancer survival between low-risk and high
      risk patient groups (p = 3.8 * 10). CONCLUSIONS: This study validates the CCP
      score and the prognostic score as independent predictors of lung cancer death in
      patients with early stage lung adenocarcinoma treated with surgery alone.
      Patients with resected stage I lung adenocarcinoma and a high prognostic score
      may be candidates for adjuvant therapy to reduce cancer-related mortality.

PMID- 25396680
TI  - Channeling motion of gold nanospheres on a rippled glassed surface.
AB  - Gold nanospheres have been manipulated by atomic force microscopy on a rippled
      glass surface produced by ion beam sputtering and coated with an ultrathin (10 nm
      thick) graphitic layer. This substrate is characterized by irregular wavy grooves
      running parallel to a preferential direction. Measurements in ambient conditions
      show that the motion of the nanoparticles is confined to single grooves
      ('channels'), along which the particles move till they are trapped by local
      bottlenecks. At this point, the particles cross the ripple pattern in a series of
      consecutive jumps and continue their longitudinal motion along a different
      channel. Moreover, due to the asymmetric shape of the ripple profiles, the jumps
      occur in the direction of minimum slope, resembling a ratchet mechanism. Our
      results are discussed, extending a collisional model, which was recently
      developed for the manipulation of nanospheres on flat surfaces, to the specific
      geometry of this problem. 

PMID- 25396682
TI  - Melanocytic tumour with unknown malignant potential--a Danish study of 67
      patients.
AB  - The aim of our single clinical centre study was to evaluate the risk of local
      metastases, lymph node metastases and distant metastases in patients diagnosed
      with melanocytic tumour with unknown malignant potential (MELTUMP). Furthermore,
      we evaluated several histologic tumour characteristics as potential predictive
      factors. From 1 January 1999 to 30 June 2011, a total of 67 consecutive patients
      were diagnosed with MELTUMP in our hospital. In this study, all the pathology
      slides were reviewed by the same independent expert dermatopathologist. All data
      were retrieved from patient charts. Four patients (6%) had regional nodal
      dissemination at the time of the diagnosis. Furthermore, one patient (1%)
      developed regional spread during follow-up and another patient (1%) died from
      distant metastases 1 year after diagnosis. We found no predictive factors with
      regard to histologic tumour characteristics. Our study confirms the low malignant
      potential of MELTUMP. We found a low risk of nodal metastasis and mortality from
      distant metastasis during follow-up. We recommend that all patients diagnosed
      with MELTUMP should be treated according to the guidelines for invasive melanoma.

PMID- 25396683
TI  - The Mayo Clinic experience with the use of kinase inhibitors, ipilimumab,
      bevacizumab, and local therapies in the treatment of metastatic uveal melanoma.
AB  - Uveal melanoma is the most common neoplasm of the adult eye. Many patients will
      develop metastatic disease, for which there is no standard of care. Therefore, we
      sought to review our experience with treating this neoplasm. We retrospectively
      reviewed all of the cases of metastatic uveal melanoma seen at the Mayo Clinic,
      Rochester, Minnesota, USA, between 1 January 2000 and 1 August 2013. Overall
      survival rates were compared among patients treated with local therapies (LTs),
      ipilumumab, bevacizumab, or kinase inhibitors. A total of 101 patients were
      included in the study, among whom 59% were male; the median age was 62 years
      (interquartile range 54-71), and 92% had an Eastern Cooperative Oncology Group
      performance status of 0-1. Treatment with LT was associated with increased median
      overall survival: 26 months (n=46; interquartile range 20-44) versus 9.1 months
      (n=55; 4.1-20, P<0.0001). No significant survival benefit was seen with the use
      of bevacizumab (25 vs. 12 months; P=0.09), ipilimumab (28 vs. 13 months; P=0.07),
      or kinase inhibitors (24 vs. 13 months; P=0.06). Multivariate analysis showed LT
      as the only therapy to significantly improve survival (risk ratio 0.23,
      P=0.0003). However, these patients had better markers of prognosis at the time of
      treatment. These data suggest that survival was improved in patients who were
      amenable to LTs; however, they had better prognostic markers at diagnosis of
      metastatic disease. Ongoing prospective clinical trials will define the roles of
      these novel agents in this patient population. 

PMID- 25396685
TI  - Full propagation-vector star antiferromagnetic order in quantum spin trimer
      system Ca3CuNi2(PO4)4.
AB  - We show that the antiferromagnetic structure in the quantum spin trimer system
      Ca3CuNi2(PO4)4 is based on both arms of propagation vector k star {[1/2, 1/2, 0],
      [-1/2, 1/2, 0]} of the paramagnetic space group C2/c. The structure is generated
      by a symmetric direction of the order parameter of two-dimensional irreducible
      representation of C2/c with one active magnetic mode and corresponds to the
      Shubnikov magnetic space group Ca2/c. We reveal the relation between
      representation analysis in the propagation vector formalism and Shubnikov
      symmetry. These types of multi-k structures are extremely rarely observed
      experimentally. To further prove the specific magnetic structure we have
      performed the calculations of the spin expectation values in the isolated Ni(2+)
      Cu(2+)-Ni(2+) trimer with realistic Hamiltonian. The calculated spin values <SNi>
      = 0.9 and <SCu> = 0.3 are within 10% accuracy in agreement with the experiment,
      providing a strong complementary argument in favor of a multi-arm magnetic
      structure.

PMID- 25396684
TI  - Objective responses can be obtained by CTLA-4 inhibition in metastatic melanoma
      after BRAF inhibitor failure.
AB  - The aim of this study was to determine the activity of ipilimumab (ipi)-based
      therapy after treatment failure with a BRAF inhibitor (BRAFi). Sixty-four
      patients with unresectable stage III or stage IV BRAF V600-mutant melanoma who
      were treated sequentially with a BRAFi and ipi-based therapy [ipi as monotherapy
      or ipi in combination with an autologous mRNA electroporated dendritic cell
      vaccine (TriMixDC-MEL)] were identified. Thirty-three patients had been treated
      with a BRAFi before ipi-based therapy (BRAFi-first), and 31 patients had been
      treated with ipi-based therapy first (ipi-first). In patients treated with a
      BRAFi first (n=33), the best response on sequential ipi-based therapy was three
      complete responses and six partial responses (best objective response rate of
      27%). In patients treated with ipi-based therapy first (n=31), the best response
      on ipi-based therapy was 0 complete response and four partial responses (best
      objective response rate of 13%). The response rate did not differ significantly
      between the two groups (P=0.14). The median overall survival from the start of
      ipi-based therapy was 10 months (95% confidence interval: 5.7-14.3) in the BRAFi
      first group and 12.3 months (95% confidence interval: 7.4-17.2) in the ipi-first
      group (P=0.34). We report that objective tumor responses to ipi-based
      immunotherapy can still be obtained after progression has occurred upon treatment
      with a BRAFi. A part of this observation might be related to the results obtained
      with a combination of ipi and TriMixDC-MEL. 

PMID- 25396686
TI  - Clinical applications of diaphragm ultrasound: moving forward.
AB  - Establishing the correct time of weaning from mechanical ventilation is a crucial
      issue in the clinical practice. The difficult process of weaning can be due to
      pathological conditions that result in an imbalance between respiratory-muscle
      strength and respiratory load. Recently it has been suggested that ultrasound
      measurements of diaphragm muscle thickening in inspiration during weaning could
      provide an estimation of extubation success. Bedside ultrasonography,
      particularly sonographic evaluation of the diaphragm by measuring the percentage
      variation of diaphragm thickness (tdi) between end-inspiration and end-expiration
      (Deltatdi%), has become a valuable tool in the management of intensive care unit
      patients. This non-invasive, low-cost and fast to perform technique seems to
      predict with a good accuracy the extubation failure. Some limitations derive from
      the difficulty to determine the maximum (end inspiratory) and minimum (end
      expiratory) tdi observing a dynamic image in B-mode, in particular in non
      collaborating patients. In addition, some dynamic situations causing extubation
      failure could not be predicted by an ultrasound measure performed at the
      beginning of the weaning trial. Nowadays the technique proposed remains a useful
      tool for helping the prediction of extubation failure. It would be useful in the
      future to set up multicentric studies with a standardised description of the
      procedure and serial measurements in different timing during the weaning trial.
      Furthermore, randomized controlled trials to evaluate the efficiency of Deltatdi%
      versus other indexes in predicting extubation failure are needed. 

PMID- 25396687
TI  - Pulmonary endarterectomy: the lancet first, tears for pills.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease
      due to the incomplete resolution of pulmonary emboli, leading to right heart
      failure, with a poor survival. Pulmonary endarterectomy (PEA) is the operation of
      choice for CTEPH. As there are no well-defined criteria to discriminate
      surgically accessible from inaccessible obstructive lesions, the operability
      assessment relies on the surgeon's experience. The recommended algorithms to
      perform a correct diagnosis of CTEPH still suggest the lung ventilation/perfusion
      scan, despite advances in computed tomography with 3-D reconstruction and
      magnetic resonance imaging. Selective pulmonary angiography is the gold standard
      to assess operability in CTEPH. Medical therapy should not be considered an
      alternative to PEA, as it should be reserved to patients with either peripheral
      disease, deemed inoperable by an experienced PEA surgeon, or persistent/recurrent
      pulmonary hypertension after PEA. Lung transplantation, when indicated, still
      represents a viable option for patients with either inoperable CTEPH or CTEPH
      with concomitant severe parenchymal lung disease that contraindicates PEA. The
      outcome of operable CTEPH is still best predicted after surgery. Remarkably, the
      recovery of exercise capacity is not as immediate as hemodynamic improvement,
      underlining the importance of early identification of surgical candidates before
      physical deconditioning. 

PMID- 25396681
TI  - Versatile roles of k63-linked ubiquitin chains in trafficking.
AB  - Modification by Lys63-linked ubiquitin (UbK63) chains is the second most abundant
      form of ubiquitylation. In addition to their role in DNA repair or kinase
      activation, UbK63 chains interfere with multiple steps of intracellular
      trafficking. UbK63 chains decorate many plasma membrane proteins, providing a
      signal that is often, but not always, required for their internalization. In
      yeast, plants, worms and mammals, this same modification appears to be critical
      for efficient sorting to multivesicular bodies and subsequent lysosomal
      degradation. UbK63 chains are also one of the modifications involved in various
      forms of autophagy (mitophagy, xenophagy, or aggrephagy). Here, in the context of
      trafficking, we report recent structural studies investigating UbK63 chains
      assembly by various E2/E3 pairs, disassembly by deubiquitylases, and specifically
      recognition as sorting signals by receptors carrying Ub-binding domains, often
      acting in tandem. In addition, we address emerging and unanticipated roles of
      UbK63 chains in various recycling pathways that function by activating nucleators
      required for actin polymerization, as well as in the transient recruitment of
      signaling molecules at the plasma or ER membrane. In this review, we describe
      recent advances that converge to elucidate the mechanisms underlying the wealth
      of trafficking functions of UbK63 chains. 

PMID- 25396688
TI  - Smoking cessation, anxiety, mood and quality of life: reassuring evidences.
AB  - A close and complex relationship between smoking and mental health problems was
      found. Different hypotheses have been proposed to explain these associations: 1)
      smoking and poor mental health may share common causes (genetic factors or
      environmental mechanisms); 2) for people with poor mental health smoking is a
      coping strategy to regulate psychiatric symptoms; 3) smokings worsen mental
      health. Moreover, smokers with psychiatric disorders may have more difficulty
      quitting and patients with mental diseases who received mental health treatment
      within the previous year were more likely to stop smoking than those not
      receiving treatment. Taylor et al. hypothesized that quitting smoking might
      improve rather than exacerbate mental health, because it allows to avoid multiple
      episodes of negative affect induced by withdrawal. With the aim to verify this
      hypothesis, they conducted a systematic review and meta-analysis on longitudinal
      studies (randomized controlled trials and cohort studies) in which the difference
      in change in mental health between subjects who stop smoking and subjects who
      continue to smoke has been explored. A total of 26 longitudinal studies
      evaluating anxiety, depression, mixed anxiety and depression, positive effect,
      psychological quality of life, and stress have been included. The study results
      provided enough evidence to assure that quitting smoking is associated with a
      reduction of depression, anxiety, and stress, with an improvement of
      psychological quality of life and positive affect compared with continuing to
      smoke. The strength of association was similar for both the general population
      and study enrolled populations, including those with mental health disorders. The
      results of this meta-analysis have direct clinical implications: the benefits for
      mental health could motivate physicians and patients to take into account the
      possibility of smoking cessation. 

PMID- 25396689
TI  - Daytime Sleepiness Is Associated With Reduced Integration of Temporally Distant
      Outcomes on the Iowa Gambling Task.
AB  - Sleep deprivation is associated with performance decrements on some measures of
      executive functioning. For instance, sleep deprivation results in altered
      decision making on the Iowa Gambling Task. However, it is unclear which component
      processes of the task may be driving the effect. In this study, Iowa Gambling
      task performance was decomposed using the Expectancy-Valence model. Recent sleep
      debt and greater daytime sleepiness were associated with higher scores on the
      updating parameter, which reflects the extent to which recent experiences are
      emphasized over remote ones. Findings suggest that the effects of insufficient
      sleep on IGT performance are due to shortening of the time horizon over which
      decisions are integrated. These findings may have clinical implications in that
      individuals with sleep problems may not integrate more temporally distant
      information when making decisions. 

PMID- 25396690
TI  - Measurement equivalence of neuropsychological tests across education levels in
      older adults.
AB  - OBJECTIVE: The objective was to determine whether neuropsychological tests
      provide an equivalent measure of the same psychological constructs in older
      adults with low versus higher levels of education. METHOD: Confirmatory factor
      analysis was used to evaluate the fit of a three-factor model (Verbal Ability,
      Visuospatial Ability, Long-Term Retention) to scores from the neuropsychological
      battery of the Canadian Study of Health and Aging (CSHA). Measurement equivalence
      of the model across lower educated (LE; <=8 years) and higher educated (HE; >=9
      years) participants was evaluated using invariance testing. RESULTS: The
      measurement model demonstrated adequate fit across LE and HE samples but the
      loadings of the 11 tests onto the three factors could not be constrained equally
      across groups. Animal Fluency and the Token Test were identified as noninvariant
      tests of Verbal Ability that, when freed from constraints, produced a partial
      metric invariance model. Scalar invariance testing identified the Buschke Cued
      Recall Test and Block Design as measures with invariant factor loadings but
      noninvariant intercepts. Analyses were replicated in age- and sex-matched
      subsamples. CONCLUSIONS: Metric and scalar invariance across HE and LE samples
      was achieved for seven of the 11 tests in the CSHA battery. Animal Fluency and
      the Token Test were noninvariant measures of Verbal Ability, suggesting that
      cognitive processes underlying performance on these tests may vary as a function
      of education. In addition, scores from Block Design and the Buschke Cued Recall
      Test were observed to differ in their scale of measurement between HE and LE
      examinees.

PMID- 25396691
TI  - Translation of cell therapies to the clinic: characteristics of cell suspensions
      in large-diameter injection cannulae.
AB  - With the use of cell replacement therapies as a realistic prospect for conditions
      such as Parkinson's and Huntington's diseases, the logistics of the delivery of
      cell suspensions to deep brain targets is a topic for consideration. Because of
      the large cannulae required for such procedures, we need to consider the behavior
      of cell suspensions within the cannulae if we are to ensure that the injected
      cells are distributed as intended within the target tissue. We have investigated
      the behavior of primary embryonic cell suspensions of neural tissue, in cannulae
      of different diameters, using a protocol designed to mimic the handling and
      injection of cells during clinical application. Internal cannula diameter had a
      large effect on the distribution of cells during their dispensation from the
      syringe. In vertical or near vertical cannulae, cells settled toward the tip of
      the needle, and were dispensed unevenly, with the majority of cells emerging in
      the first 10-20% of the injectate. In horizontal or near-horizontal cannulae, we
      observed the opposite effect, such that few cells were dispensed in the first 80%
      of the injectate, and the majority emerged in the final 10-20%. Use of a glass
      cannula showed that the results obtained using the horizontal cannula were caused
      by settling and adherence of the cells on the side of the cannulae, such that
      during dispensation, the overlying, cell-free solution was dispensed first, prior
      to the emergence of the cells. We show that the behavior of cells in such
      cannulae is affected by the cannula diameter, and by the material of the cannula
      itself. In horizontal cannulae, uneven expulsion of cells from the needle can be
      ameliorated by regular rotation of the cannula during the procedure. We discuss
      the potential impact of these observations on the translation of cell therapies
      to the clinic. 

PMID- 25396692
TI  - Functional magnetic resonance imaging response of targeted tumor burden and its
      impact on survival in patients with hepatocellular carcinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate response of the targeted tumor
      burden by functional magnetic resonance imaging (MRI) including volumetric
      diffusion-weighted imaging and volumetric contrast-enhanced MRI (CE-MRI) and its
      impact on survival in patients with hepatocellular carcinoma treated with intra
      arterial therapy (IAT). MATERIALS AND METHODS: This institutional review board
      approved, Health Insurance Portability and Accountability Act-compliant
      retrospective study included 157 hepatocellular carcinoma lesions in 97 patients
      (78 men and 19 women; mean age, 64 years) treated with IAT. All patients had
      pretreatment and 3- to 4-week follow-up MRI with diffusion-weighted imaging and
      CE-MRI. All lesions 2 cm or larger that were targeted during the first session of
      IAT were segmented using research software (MR-Oncotreat) to determine targeted
      tumor burden relative to liver volume (%). Targeted tumor burden was stratified
      into low (<=10%) or high (>10%). Response using volumetric functional apparent
      diffusion coefficient (ADC; increase by >=25%) and CE-MRI (decrease by >=50% and
      >=65% in arterial and venous enhancement [VE], respectively) was assessed in all
      targeted tumors (range, 1-11) using paired t tests. Kaplan-Meier survival
      analysis was performed and log-rank test was used to compare pairs of survival
      curves. Multivariate Cox regression analysis was performed to determine the
      simultaneous effect of treatment response and tumor burden on survival after
      adjusting for age, sex, and Child Pugh status. RESULTS: There was a significant
      increase in volumetric ADC (median, 15%; P < 0.001) and a decrease in volumetric
      arterial enhancement (AE) and VE (median AE, -43% and portal venous phase (PVP), 
      29%, respectively; P < 0.001) 3 to 4 weeks after treatment in the targeted tumor
      burden. Multivariable Cox regression demonstrated that both ADC response and low
      tumor burden were independently associated with greater survival (hazard ratios,
      0.53 and 0.55; P values, 0.025 and 0.016, respectively) after adjustment for age,
      sex, and Child Pugh status. Multivariable Cox regression models demonstrated no
      statistically significant relationship between AE response and survival after
      adjusting for tumor burden. However, multivariable Cox regression demonstrated
      that VE response was associated with greater survival only in those with low
      tumor burden (hazard ratio, 0.10; P = 0.001), indicating a strong interaction
      between VE response and tumor burden. CONCLUSION: Quantifying targeted tumor
      burden is important in predicting patient survival when using functional MRI
      metrics in assessing treatment response.

PMID- 25396693
TI  - Facial emotion recognition deficits following moderate-severe Traumatic Brain
      Injury (TBI): re-examining the valence effect and the role of emotion intensity.
AB  - Many individuals who sustain moderate-severe traumatic brain injuries (TBI) are
      poor at recognizing emotional expressions, with a greater impairment in
      recognizing negative (e.g., fear, disgust, sadness, and anger) than positive
      emotions (e.g., happiness and surprise). It has been questioned whether this
      "valence effect" might be an artifact of the wide use of static facial emotion
      stimuli (usually full-blown expressions) which differ in difficulty rather than a
      real consequence of brain impairment. This study aimed to investigate the valence
      effect in TBI, while examining emotion recognition across different intensities
      (low, medium, and high). METHOD: Twenty-seven individuals with TBI and 28 matched
      control participants were tested on the Emotion Recognition Task (ERT). The TBI
      group was more impaired in overall emotion recognition, and less accurate
      recognizing negative emotions. However, examining the performance across the
      different intensities indicated that this difference was driven by some emotions
      (e.g., happiness) being much easier to recognize than others (e.g., fear and
      surprise). Our findings indicate that individuals with TBI have an overall
      deficit in facial emotion recognition, and that both people with TBI and control
      participants found some emotions more difficult than others. These results
      suggest that conventional measures of facial affect recognition that do not
      examine variance in the difficulty of emotions may produce erroneous conclusions
      about differential impairment. They also cast doubt on the notion that
      dissociable neural pathways underlie the recognition of positive and negative
      emotions, which are differentially affected by TBI and potentially other
      neurological or psychiatric disorders.

PMID- 25396694
TI  - A dynamical systems analysis of assisted and unassisted anterior and posterior
      hand-held load carriage.
AB  - Load carriage is recognised as a primary occupational factor leading to slip and
      fall injuries, and therefore assessing balance maintenance during such tasks is
      critical in assessing injury risk. Ten males completed 55 strides under five
      carriage conditions: (1) unassisted anterior, (2) unassisted posterior, (3)
      assisted anterior, (4) assisted posterior and (5) unloaded gait (UG). Kinematic
      data were recorded from markers affixed to landmarks on the right side of each
      participant, in order to calculate segment angles for the foot, shank, thigh and
      pelvis. Continuous relative phase (CRP) variability was calculated for each
      segment pair and local dynamic stability was calculated for each segment in all
      three movement planes. In general, irrespective of the assistive device or
      movement plane, anterior load carriage was most stable (lower CRP variability and
      maximum finite-time Lyapunov exponents). Moreover, load carriage was less
      dynamically stable than UG, displaying the importance of objectively
      investigating safe load carriage practices. PRACTITIONER SUMMARY: Dynamical
      systems analyses were used to comprehensively evaluate the stability of various
      handheld load carriage methods. In general, anterior load carriage was
      significantly more stable than posterior load carriage,Mover's assistive device
      had small but beneficial effects on stability, and load carriage was less stable
      than UG.

PMID- 25396695
TI  - Global agenda, local health: including concepts of health security in
      preparedness programs at the jurisdictional level.
AB  - The Global Health Security Agenda's objectives contain components that could help
      health departments address emerging public health challenges that threaten the
      population. As part of the agenda, partner countries with advanced public health
      systems will support the development of infrastructure in stakeholder health
      departments. To facilitate this process and augment local programs, state and
      local health departments may want to include concepts of health security in their
      public health preparedness offices in order to simultaneously build capacity.
      Health security programs developed by public health departments should complete
      projects that are closely aligned with the objectives outlined in the global
      agenda and that facilitate the completion of current preparedness grant
      requirements. This article identifies objectives and proposes tactical local
      projects that run parallel to the 9 primary objectives of the Global Health
      Security Agenda. Executing concurrent projects at the international and local
      levels in preparedness offices will accelerate the completion of these objectives
      and help prevent disease epidemics, detect health threats, and respond to public
      health emergencies. Additionally, future funding tied or related to health
      security may become more accessible to state and local health departments that
      have achieved these objectives. 

PMID- 25396696
TI  - Experimental liver protection of n-butanolic extract of Astragalus monspessulanus
      L. on carbon tetrachloride model of toxicity in rat.
AB  - OBJECTIVE: To investigate the hepatoprotective potential of n-butanolic extract
      of Astragalus monspessulanus L. (EAM) against in-vitro/in-vivo carbon
      tetrachloride (CCl4)-induced liver damage in rats. Silymarin was used as a
      positive control. METHODS AND RESULTS: The in-vitro experiments were carried out
      in primary isolated rat hepatocytes first incubated with CCl4 (86 umol/l).
      Hepatic injury was discerned by a decrease in cell viability and cell glutathione
      (GSH) levels, an increase in lactate dehydrogenase leakage into the medium, and
      an elevation in malondialdehyde (MDA) quantity. Cell pre-incubation with EAM (1
      ug/ml and 10 ug/ml) significantly ameliorated the CCl4-induced liver damage. In
      vivo rats were challenged orally with CCl4 (10% solution in olive oil) alone and
      after 7 days pre-treatment with EAM (100 mg/kg body weight per day, oral gavage).
      CCl4 damage was judged by an increased production of MDA, depletion of cell GSH,
      and a decrease in cell antioxidant defense system. EAM pre-treatment normalizes
      the activities of the antioxidant enzymes and the levels of GSH and MDA. These
      data are supported by the histopathological examination. CONCLUSION: These
      results indicate that EAM has a similar significant protective effect, in vitro
      and in vivo, against CCl4 induced hepatotoxicity in rat as silymarin.This may be
      due to its antioxidant and membrane stabilizing properties.

PMID- 25396697
TI  - Accuracy of the Emotion Thermometers (ET) screening tool in patients undergoing
      surgery for upper gastrointestinal malignancies.
AB  - Distress is common in patients with gastrointestinal cancers. Most conventional
      scales are too long for routine clinic use. We tested the Emotion Thermometers
      (ET) tool, a brief visual-analogue scale. There are four emotional upset
      thermometers: distress, anxiety, depression, and anger. Sixty-nine surgical
      patients were recruited from an academic hospital clinic in 2012; 64 had complete
      data for Beck depression inventory and ET. The sample size was modest due to the
      specialist nature of the sample. We examined sensitivity, specificity, and area
      under the receiver-operator-curve. A dimensional multi-domain approach to
      screening for emotional disorders is preferable to using the distress thermometer
      alone and can be achieved with little extra time burden to clinicians. The ET is
      a diagnostic tool that is primarily designed for screening to identify cancer
      patients who would benefit by enhanced psychosocial care. 

PMID- 25396698
TI  - Coping Styles, Pain Expressiveness, and Implicit Theories of Chronic Pain.
AB  - Whereas some individuals use active coping strategies and are able to adaptively
      cope with their pain, others use passive strategies and catastrophic appraisals,
      which are often associated with increased displays of pain behavior and negative
      pain-related outcomes. To investigate attribution-based implicit theories as a
      potential underlying mechanism that might affect coping success, we hypothesized
      that pain patients with an incremental implicit theory of pain (i.e., view pain
      as malleable) would have more active coping strategies, lower levels of pain
      expressiveness, and better pain-related outcomes than those with an entity
      implicit theory of pain (i.e., view pain as nonmalleable). Patients with chronic
      back pain undergoing a functional assessment completed a variety of self-report
      measures and participated in a pain-inducing physiotherapy procedure. The results
      revealed those with an incremental theory of pain used more active coping
      strategies, displayed less pain behavior, and reported better pain-related
      outcomes (e.g., lower levels of depression) than individuals with an entity
      theory of pain. The findings suggest implicit theories of pain may represent an
      underlying social-cognitive mechanism linked to important coping, emotional, and
      expressive reactions to chronic pain. Identifying such a mechanism may provide
      valuable information for the assessment and treatment of chronic pain. 

PMID- 25396699
TI  - A major stream in mental health in undergraduate nursing programmes: identifying
      the benefits and acknowledging the innovation.
AB  - The literature demonstrates the problems mental health nursing has faced in
      securing sufficient graduate nurses to meet current and projected workforce
      needs. Deficiencies in educational preparation have been identified as a
      significant contributing factor. A major stream in mental health nursing has been
      introduced into undergraduate Bachelor of Nursing programmes as one strategy to
      address this problem. To-date, 11 streams have been introduced into Australian
      universities and no evaluations of the impact of these initiatives have been
      published as yet. This qualitative research was undertaken to explore the
      implementation and outcomes of major streams. In-depth telephone interviews were
      undertaken with participants from 10 universities, to explore their experiences
      with and opinions of this initiative. This paper specifically addresses the
      perceived benefits. Qualitative data analysis revealed many benefits to the major
      in promoting the value of, and encouraging interest in mental health nursing for
      undergraduate students. Four main themes were identified: (1) benefits to
      students; (2) benefits to the university; (3) benefits to industry; and (4)
      innovative approaches to education. The findings suggest the major in mental
      health nursing can contribute to addressing workforce problems in mental health
      nursing. 

PMID- 25396700
TI  - The supracerebellar-transtentorial approach to posteromedial temporal lesions in
      children with refractory epilepsy.
AB  - OBJECT: Operations on tumors of the posteromedial temporal (PMT) region, that is,
      on those arising from the posterior parahippocampal, fusiform, and lingual gyri,
      are challenging to perform because of the deep-seated location of these tumors
      between critical cisternal neurovascular structures and the adjacent temporal and
      occipital cortexes. Traditional surgical approaches require temporal or occipital
      transgression, retraction, or venous sacrifice. These approaches may result in
      unintended complications that should be avoided. To avoid these complications,
      the supracerebellar-transtentorial (SCTT) approach to this region has been used
      as an effective alternative treatment in adult patients. The SCTT approach uses a
      sitting position that offers a direct route to the posterior fusiform and lingual
      gyri of the temporal lobe. The authors report the feasibility, safety, and
      efficacy of this approach, using a modified lateral park-bench position in a
      small cohort of pediatric patients. METHODS: The authors carried out a
      retrospective case review of 5 consecutive patients undergoing a paramedian SCTT
      approach between 2009 and 2014 at the authors' institution. RESULTS: The SCTT
      approach in the park-bench position was used in 3 boys and 2 girls with a mean
      age of 7.8 years (range 13 months to 16 years). All patients presented with a
      seizure disorder related to a tumor in a PMT region involving the parahippocampal
      and fusiform gyri of the left (n = 3) or right (n = 2) temporal lobe. No
      procedure-related complications were observed. Gross-total resection and control
      of seizures were achieved in all cases. Tumor classes and types included 1 Grade
      II astrocytoma, 1 pleomorphic xanthoastrocytoma, 1 ganglioglioma, and 2
      glioneural tumors. None of the tumors had recurred by the mean follow-up of 22
      months (range 1-48 months). Outcomes of epileptic seizures were excellent, with
      seizure symptoms in all 5 patients scoring in Engel Class IA. CONCLUSIONS: The
      SCTT approach represents a viable option when resecting tumors in this region,
      providing a reasonable working corridor and low morbidity. The authors'
      experience in a cohort of pediatric patients demonstrates that complete resection
      of the lesions in this location is feasible and is safe when involving an
      approach that involves using a park-bench lateral positioning.

PMID- 25396701
TI  - Identical twins with lumbosacral lipomyelomeningocele.
AB  - Lipomyelomeningocele, a congenital spine defect, is presented as skin-covered
      lipomatous tissue that attaches to the cord in different ways according to its
      subtypes. Unlike other types of neural tube defects, the exact cause of this
      birth defect has not been confirmed yet, but it is proposed to be a
      multifactorial disease with involvement of both genetic and environmental
      factors. The authors describe identical twins with lipomyelomeningocele of the
      same subtype and location without any familial history of similar abnormality.
      Therefore, the same genetic and/or environmental risk factors could have played a
      part in their condition. 

PMID- 25396702
TI  - The supraorbital eyebrow approach in children: clinical outcomes, cosmetic
      results, and complications.
AB  - OBJECT: The supraorbital eyebrow approach utilizes an eyebrow skin incision to
      fashion a supraorbital craniotomy for exposure of the subfrontal corridor. This
      provides anterolateral access to surgical lesions in the anterior cranial fossa,
      parasellar regions, brainstem, and medial temporal lobe. With use of the
      endoscope, further areas can be accessed. This approach has been applied
      effectively in adults, but questions remain about its use in children
      specifically with regard to adequate working space, effectiveness for achieving
      the desired results, cosmesis, and complications. METHODS: The authors conducted
      a retrospective review of more than 450 cases involving patients of all ages who
      had undergone a supraorbital eyebrow approach performed by the senior author
      (C.T.) from 1995 to 2013. Only cases involving patients younger than 18 years
      with a minimum follow-up of 6 weeks were included in this study. All inpatient
      and outpatient records were retrospectively reviewed and clinical/operative
      outcomes, cosmetic results, and complications were recorded. In the present
      article, the authors briefly describe the surgical approach and highlight any
      differences in applying it in children. RESULTS: Fifty-four pediatric patients
      who had undergone a supraorbital eyebrow approach met inclusion criteria. The
      pathological conditions consisted mostly of tumors or other resectable lesions.
      In a total of 51 resectable lesions, 44 surgeries resulted in a gross-total
      (100%) resection and 7 cases resulted in subtotal (50%-99%) resection. The
      endoscope assisted and expanded visualization or provided access to areas not
      reached by standard microscopic visualization in all cases. Cosmetic outcomes
      were excellent. In all cases, the incisional scar was barely visible at 6 weeks.
      In 3 cases a minor bone defect was observed on the forehead. Given the small size
      of the frontal sinus in children, no frontal sinus breaches occurred.
      Additionally, no CSF leak or wound infection was identified. CONCLUSIONS: The
      supraorbital eyebrow approach is extremely effective in achieving desired results
      in properly selected cases in patients of all pediatric age ranges, from infants
      to teenagers. There is sufficient working space for the endoscope and all
      instruments, allowing for endoscopic assistance and bimanual surgical technique.
      Cosmetic results are excellent, and complications related to the approach are
      minimal.

PMID- 25396703
TI  - Triceps motor branch transfer for isolated traumatic pediatric axillary nerve
      injuries.
AB  - OBJECT: Transfer of the triceps motor branch has been used for treatment of
      isolated axillary nerve palsy in the adult population. However, there are no
      published data on the effectiveness of this procedure in the pediatric population
      with traumatic injuries. The authors reviewed demographics and outcomes in their
      series of pediatric patients who underwent this procedure. METHODS: Six patients
      ranging in age from 10 to 17 years underwent triceps motor branch transfer for
      the treatment of isolated axillary nerve injuries between 4 and 8 months after
      the inciting injury. Deltoid muscle strength was evaluated using the modified
      British Medical Research Council (MRC) grading system. Shoulder abduction at last
      follow-up was measured. RESULTS: The mean duration of follow-up was 38 months.
      The average postoperative MRC grading of deltoid muscle strength was 3.6 +/- 1.3.
      The median MRC grade was 4. One patient who did not achieve an MRC grade of 3
      suffered multiple injuries from high-velocity trauma. Unlike in the adult
      population, age, body mass index of the patient, and delay from injury to surgery
      were not significant factors affecting the outcome of the procedure. CONCLUSIONS:
      In the pediatric population with traumatic injuries, isolated axillary nerve
      injury treated with triceps motor branch transfer can result in good outcomes.

PMID- 25396704
TI  - Chiari malformation I and autism spectrum disorder: an underrecognized
      coexistence.
AB  - OBJECT: Patients with symptomatic Chiari malformation Type I (CM-I) frequently
      present with headaches, neck pain, difficulty swallowing, and balance
      disturbances. In children with autism spectrum disorder (ASD), diagnosing CM-I
      can be a challenging task. Moreover, even if symptomatic, some patients do not
      undergo further evaluation or management, as their presentations are attributed
      to autism and its myriad symptoms. Therefore, cranial MRI findings were reviewed
      after evaluating and treating patients with coexisting ASD and CM-I. In this
      paper, the authors report on 5 children with ASD and symptomatic CM-I, including
      their clinical presentation, imaging studies, management, and outcomes, and
      discuss the likely underrecognized coexistence of these conditions. METHODS: All
      pediatric patients with ASD and cranial MRI conducted for any reason in the
      period from 1999 to 2013 were considered for analysis. All cases with concomitant
      symptomatic CM-I were eligible for this retrospective analysis. RESULTS: One
      hundred twenty-five pediatric patients diagnosed with ASD had undergone MRI, and
      9 of them had evidence of cerebellar tonsillar herniation. Five patients were
      symptomatic and underwent suboccipital craniectomy, a C-1 or a C-1 and C-2
      laminectomy, and duraplasty with bovine pericardium or Type I collagen allograft.
      There were no intraoperative complications. All patients showed symptom
      improvement and/or resolution of presenting symptoms, which included headache,
      dysphasia, speech, and irritability. CONCLUSIONS: There is no identified cause of
      autism. Children with ASD can be difficult to assess specifically in a
      neurological examination. Thus, cranial MRI considered when completing a
      comprehensive diagnostic evaluation. While cranial MRI is not a routine part of
      ASD evaluation, this study demonstrates that CM-I and ASD may coexist and be
      underrecognized. The study reinforces the importance of a comprehensive medical
      evaluation designed to elucidate neurological findings in children with impaired
      communication abilities and suggests the judicious use of neuroimaging.

PMID- 25396705
TI  - Dysphoria and smoking among treatment seeking smokers: the role of smoking
      related inflexibility/avoidance.
AB  - BACKGROUND: Emerging data suggest that dysphoria is one facet of depression that
      is especially related to various aspects of cigarette smoking. However, it is
      presently unknown what emotional processes may account for these relations.
      OBJECTIVES: In the current cross-sectional study, the impact of avoidance and
      inflexibility to smoking (AIS), a smoking-specific form of experiential
      avoidance, was tested on the relationship of dysphoria to four specific smoking
      processes that are key factors in cessation: perceived barriers to cessation,
      severity of problems during prior quit attempts, negative reinforcement smoking
      expectancies, and motivation to quit smoking. METHODS: Participants (n = 465)
      were treatment-seeking adult daily smokers. Relative indirect effects were
      subjected to bootstrap analyses to test direct and indirect effects of dysphoria
      on smoking processes. RESULTS: After controlling for gender, nicotine dependence
      severity, drinking problems, cannabis use, negative affectivity, tobacco-related
      medical problems, and AIS, dysphoria remained directly, positively related to
      perceived barriers and cessation problems. Additionally, dysphoria was
      indirectly, positively related to perceived barriers, cessation problems,
      negative reinforcement smoking expectancies, and motivation to quit indirectly
      through higher levels of AIS. CONCLUSION: In the context of dysphoria, AIS may
      explain a wide range of clinically-relevant smoking processes.

PMID- 25396707
TI  - Epidemiology of hospital-treated injuries sustained by fitness participants.
AB  - PURPOSE: The purpose of this study was to provide an epidemiological profile of
      injuries sustained by participants in fitness activities in Victoria, Australia,
      based on hospital admissions and emergency department (ED) presentations and to
      identify the most common types, causes, and sites of these injuries. METHOD:
      Hospital-treated fitness activity-related injury cases were identified from
      International Classification of Disease activity codes (for admissions) and from
      text narratives of injury events (for ED presentations) from 2003 to 2010,
      inclusive. Cases were categorized as being associated with aerobics/group
      exercise (n = 252), resistance/weight training (n = 830) or "other equipment"
      (motorized and general gym equipment; n = 1,156). Participation information was
      taken from the Exercise, Recreation and Sport Survey. RESULTS: Overall, 2,238
      cases were identified and 11.6% of all patients with ED presentations were
      subsequently hospitalized. Those participants with aerobics cases were generally
      female (76.6%) and aged 25 to 34 years old (35.3%), with injuries to the lower
      limbs (59.1%) and due to falls (57.9%). Resistance-training injuries increased
      significantly during the 8-year period (by 215.7%; 95% CI [133.5, 326.9]) and
      generally occurred in male participants (78.0%), in people aged 15 to 24 years
      old (36.4%), and with injuries to the upper limbs (45.1%) caused by being hit,
      struck, or crushed by weights or fellow exercisers (71.4%). The "other equipment"
      cases were equally distributed by gender; they occurred most commonly in people
      aged 15 to 24 years old (27.8%), with injuries to the lower limbs (41.5%) and due
      to falls (57.6%). Across all categories, dislocations, sprains, and strains were
      the most common injury types. CONCLUSIONS: Fitness activity-related injury
      prevention strategies should be targeted at different subgroups according to the
      type of fitness activity being undertaken.

PMID- 25396706
TI  - Medication adherence among men who have sex with men at risk for HIV infection in
      the United States: implications for pre-exposure prophylaxis implementation.
AB  - Pre-exposure prophylaxis (PrEP) is a promising HIV prevention approach for men
      who have sex with men (MSM), however non-adherence could limit its effectiveness.
      Understanding the experiences of HIV-uninfected MSM taking routine medications
      can provide valuable insights into open label PrEP adherence in real world
      settings and guide development of PrEP adherence interventions. In this study, we
      examined self-reported medication-taking experiences and facilitators and
      barriers of medication adherence among a geographically-diverse online sample of
      HIV-uninfected US MSM. Among 1480 participants, 806 (54%) reported taking
      medications regularly, of whom 80% reported taking medications for treatment and
      55% for prevention purposes. Facilitators of medication adherence included
      establishing a routine, keeping medication visible, and using a pill-box;
      barriers included forgetting, changes in routine, and being busy or away from
      home. Only 45% rated their medication-taking ability as excellent, and 36%
      reported not missing any doses in the past 30 days. In multivariable analyses,
      older men and those not reporting any adherence barriers were more likely to
      report excellent adherence, and men willing to use PrEP were more likely to
      report perfect 30-day adherence. Counseling strategies to build pill-taking
      routines and support younger MSM are suggested to maximize the public health
      impact of PrEP.

PMID- 25396708
TI  - Stimulus-classification and stimulus-action associations: Effects of repetition
      learning and durability.
AB  - It has been shown that acquired stimulus-response bindings result from at least
      two types of associations from the stimulus to the task (stimulus-task or
      stimulus-classification; S-C) and from the stimulus to the motor response
      (stimulus-response or stimulus-action; S-A). These types of associations have
      been shown to independently affect behaviour. This finding suggests that they are
      processed in different pathways or different parts of a pathway at the neural
      level. Here we test a hypothesis that such associations may be differentially
      affected by repetition learning and that such effects may be detected by
      measuring their durability against overwriting. We show that both S-C and S-A
      associations are in fact strengthened when learning is boosted by increasing
      repetitions of the primes. However, the results further suggest that associations
      between stimuli and actions have less durable effects on behaviour and that the
      durability of S-C and S-A associations is independent of repetition learning.
      This is an important finding for the understanding of the underlying mechanisms
      of associative learning and particularly raises the question of which processes
      may affect flexibility of learning. 

PMID- 25396710
TI  - Which therapeutic option for hepatitis C virus genotype 1?
AB  - OBJECTIVE: Sofosbuvir and simeprevir in combination with standard therapy are now
      available for the treatment of patients chronically infected with hepatitis C
      virus (HCV) genotype 1. With boceprevir and telaprevir, four treatment options
      are, therefore, now available to clinicians. Phase 3 studies conducted with
      simeprevir and sofosbuvir compared sustained virological response (SVR) data with
      those obtained with standard combination therapy and did not include a control
      arm. It is important to quantify the contribution of these molecules compared to
      the first direct antiviral agents available. MATERIAL AND METHODS: For HCV
      genotype 1 patients, we performed a literature review and compared all SVR data
      from phase 3 randomized placebo-controlled trials conducted with these four
      molecules according to virological characteristics (genotype, viral load) and
      patient characteristics (IL28B polymorphism, stage of fibrosis). RESULTS:
      Simeprevir and sofosbuvir provide a net gain in terms of SVR compared to
      boceprevir and telaprevir except in the case of telaprevir for treatment-naive
      HCV genotype 1b patients. Sofosbuvir achieves higher SVR rates than simeprevir
      except for treatment-naive IL28B CC patients and naive HCV genotype 1b patient.
      Further, simeprevir moderately improve SVR rates compared to telaprevir in
      treatment-naive patients with F3-F4 fibrosis and with HCV genotype 1a infection.
      CONCLUSION: Sofosbuvir and simeprevir greatly improve the virological response
      rate compared to first-generation protease inhibitors. All of these data may help
      in guiding the physician's treatment decisions, based on financial constraints
      and patient characteristics. These data can be easily updated with future
      treatment and demonstrate the contribution of new treatment regimens to achieve
      optimal SVR rates.

PMID- 25396711
TI  - Repair mechanism of osteochondral defect promoted by bioengineered chondrocyte
      sheet.
AB  - Cell sheet engineering has developed as a remarkable method for cell
      transplantation. In the field of cartilage regeneration, several studies
      previously reported that cartilage defects could be regenerated by
      transplantation of a chondrocyte sheet using cell sheet engineering. However, it
      remains unclear how such a thin cell sheet could repair a deep cartilage defect.
      We, therefore, focused on the mechanism of cartilage repair using cell sheet
      engineering in this study. Chondrocyte sheets and synovial cell sheets were
      fabricated using cell sheet engineering, and these allogenic cell sheets were
      transplanted to cover an osteochondral defect in a rat model. Macroscopic and
      histological evaluation was performed at 4 and 12 weeks after transplantation.
      Analysis of the gene expression of each cell sheet and of the regenerated tissue
      at 1 week after transplantation was performed. In addition, green fluorescent
      protein (GFP) transgenic rats were used as donors (transplanted chondrocyte
      sheets) or recipients (osteochondral defect models) to identify the cell origin
      of regenerated cartilage. Cartilage repair was significantly better in the group
      implanted with a chondrocyte sheet than in that with a synovial cell sheet. The
      results of gene expression analysis suggest that the possible factor contributing
      to cartilage repair might be TGFbeta1. Cell tracking experiments using GFP
      transgenic rats showed that the regenerated cartilage was largely composed of
      cells derived from the transplanted chondrocyte sheets. 

PMID- 25396712
TI  - Birefringence of a normal human red blood cell and related optomechanics in an
      optical trap.
AB  - A normal human red blood cell (RBC) when trapped with a linearly polarized laser,
      reorients about the electric polarization direction and then remains rotationally
      bound to this direction. This behavior is expected for a birefringent object. We
      have measured the birefringence of distortion-free RBCs in an isotonic medium
      using a polarizing microscope. The birefringence is confined to the cell's dimple
      region and the slow axis is along a diameter. We report an average retardation of
      3.5 +/- 1.5 nm for linearly polarized green light (lambda = 546 nm). We also
      estimate a retardation of 1.87 +/- 0.09 nm from the optomechanical response of
      the RBC in an optical trap. We reason that the birefringence is a property of the
      cell membrane and propose a simple model attributing the origin of birefringence
      to the phospholipid molecules in the lipid bilayer and the variation to the
      membrane curvature. We observe that RBCs reconstituted in shape subsequent to
      crenation show diminished birefringence along with a sluggish optomechanical
      response in a trap. As the arrangement of phospholipid molecules in the cell
      membrane is disrupted on crenation, this lends credence to our conjecture on the
      origin of birefringence. Dependence of the birefringence on membrane contours is
      further illustrated through studies on chicken RBCs.

PMID- 25396713
TI  - Depth-enhanced fluorescence imaging using masked detection of structured
      illumination.
AB  - There is a growing interest in imaging fluorescence contrast at depth within
      living tissues over wide fields of view and in real time. Most methods used to
      date to improve depth detection of fluorescence information involve acquisition
      of multiple images, postprocessing of the data using a light propagation model,
      and are capable of providing either depth-sectioned or tomographic fluorescence
      information. We introduce a method, termed masked detection of structured
      illumination, that allows the enhancement of fluorescence imaging at depth
      without postprocessing. This method relies on the scanning of a collimated beam
      onto a turbid medium and the physical masking of the point spread function on the
      detection arm before acquisition on a CCD camera. By preferentially collecting
      diffuse photons at a chosen source-detector range, this method enhances
      fluorescence information at depth and has the potential to form images without
      postprocessing and in real time.

PMID- 25396714
TI  - Optical imaging of fluorescent carbon biomarkers using artificial neural
      networks.
AB  - The principle possibility of extraction of fluorescence of nanoparticles in the
      presence of background autofluorescence of a biological environment using neural
      network algorithms is demonstrated. It is shown that the methods used allow
      detection of carbon nanoparticles fluorescence against the background of the
      autofluorescence of egg white with a sufficiently low concentration detection
      threshold (not more than 2 MUg/ml for carbon dots 3 MUg/ml and for nanodiamonds).
      It was also shown that the use of the input data compression can further improve
      the accuracy of solving the inverse problem by 1.5 times.

PMID- 25396715
TI  - Simultaneous determination of multi-mycotoxins in palm kernel cake (PKC) using
      liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AB  - Palm kernel cake (PKC) is a useful source of protein and energy for livestock.
      Recently, it has been used as an ingredient in poultry feed. Mycotoxin
      contamination of PKC due to inappropriate handling during production and storage
      has increased public concern about economic losses and health risks for poultry
      and humans. This concern has accentuated the need for the evaluation of
      mycotoxins in PKC. Furthermore, a method for quantifying mycotoxins in PKC has so
      far not been established. The aims of this study were therefore (1) to develop a
      method for the simultaneous determination of mycotoxins in PKC and (2) to
      validate and verify the method. A liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method using an electrospray ionisation interface (ESI) in both
      positive- and negative-ion modes was developed for the simultaneous determination
      of aflatoxins (AFB1, AFB2, AFG1 and AFG2), ochratoxin A (OTA), zearalenone (ZEA),
      deoxynivalenol (DON), fumonisins (FB1 and FB2), T-2 and HT-2 toxin in PKC. An
      optimum method using a 0.2 ml min-1 flow rate, 0.2% formic acid in aqueous phase,
      10% organic phase at the beginning and 90% organic phase at the end of the
      gradient was achieved. The extraction of mycotoxins was performed using a solvent
      mixture of acetonitrile-water-formic acid (79:20:1, v/v) without further clean
      up. The mean recoveries of mycotoxins in spiked PKC samples ranged from 81% to
      112%. Limits of detection (LODs) and limits of quantification (LOQs) for
      mycotoxin standards and PKC samples ranged from 0.02 to 17.5 MUg kg-1 and from
      0.06 to 58.0 MUg kg-1, respectively. Finally, the newly developed method was
      successfully applied to PKC samples. The results illustrated the fact that the
      method is efficient and accurate for the simultaneous multi-mycotoxin
      determination in PKC, which can be ideal for routine analysis.

PMID- 25396717
TI  - A surgical model of short bowel syndrome induces a long-lasting increase in
      pancreatic beta-cell mass.
AB  - Several surgical techniques are used nowadays as a severe treatment for obesity
      and diabetes mellitus type 2. These techniques are aggressive due to drastic
      changes in the nutrient flow and non-reversible modifications on the digestive
      tube. In this paper we present the effects of a massive intestinal resection on
      the pancreas. Results have shown that short bowel technique is less aggressive to
      normal anatomy and physiology of the intestinal tract than Gastric bypass or
      biliopancreatic diversion (e.g.). In this paper we reproduce a model of short
      bowel syndrome (SIC), with similar surgical conditions and clinical complications
      as seen in human cases. This work was conducted on normal Wistar rats, with no
      other concurrent factors, in order to determine the effects on normal pancreas
      islets. We measured pancreatic implications by histomorphometric studies, which
      included beta-cell mass by immunocytochemistry, and apoptosis/proliferation test
      with TUNEL technique and Ki-67. Briefly, we reported on an increased relative
      area of the islets of the pancreas, as well as an increase in the average size of
      islets in the SIC versus the control group. Furthermore we stated that this
      increase in size of the pancreatic islets is due to the mechanisms of
      proliferation of beta cells in animals undergoing SIC. These goals could reveal a
      direct influence of surgical modification of the digestive tract over the
      pancreatic beta cell homeostasis. In this sense, there are many potential
      stimulators of intestinal adaptation, including peptide hormones and growth
      components which are associated or involved as effectors of the endocrine
      pancreas.

PMID- 25396716
TI  - Red ginseng extract promotes the hair growth in cultured human hair follicles.
AB  - Ginseng has been shown to promote hair growth in several recent studies. However,
      its effects on human hair follicles and its mechanisms of action have not been
      sufficiently elucidated. This study aimed to investigate the hair growth
      promoting effects of red ginseng extract (RGE) and its ginsenosides. The
      proliferative activities of cultured human hair follicles treated with RGE and
      ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on
      isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity
      assays, immunoblot analysis of signaling proteins, and the determination of
      associated growth factors. We examined the ability of RGE and ginsenosides to
      protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)
      induced suppression and their effects on the expression of androgen receptor. The
      in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6
      mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix
      keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial
      cell proliferation and the associated phosphorylation of ERK and AKT. Moreover,
      RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression
      of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the
      mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that
      the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the
      negative control. In conclusion, RGE and its ginsenosides may enhance hDPC
      proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair
      matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor
      transcription. These results suggest that red ginseng may promote hair growth in
      humans. 

PMID- 25396718
TI  - Bacterial physiology: Chlamydia and the cytoskeleton.

PMID- 25396723
TI  - The fate and biogeochemical cycling of viral elements.

PMID- 25396724
TI  - AIDS advocacy and intellectual property regulation in Brazil: information and
      influence.

PMID- 25396725
TI  - Core bioactive components promoting blood circulation in the traditional Chinese
      medicine compound xueshuantong capsule (CXC) based on the relevance analysis
      between chemical HPLC fingerprint and in vivo biological effects.
AB  - Compound xueshuantong capsule (CXC) is an oral traditional Chinese herbal formula
      (CHF) comprised of Panax notoginseng (PN), Radix astragali (RA), Salvia
      miltiorrhizae (SM), and Radix scrophulariaceae (RS). The present investigation
      was designed to explore the core bioactive components promoting blood circulation
      in CXC using high-performance liquid chromatography (HPLC) and animal studies.
      CXC samples were prepared with different proportions of the 4 herbs according to
      a four-factor, nine-level uniform design. CXC samples were assessed with HPLC,
      which identified 21 components. For the animal experiments, rats were soaked in
      ice water during the time interval between two adrenaline hydrochloride
      injections to reduce blood circulation. We assessed whole-blood viscosity (WBV),
      erythrocyte aggregation and red corpuscle electrophoresis indices (EAI and RCEI,
      respectively), plasma viscosity (PV), maximum platelet aggregation rate (MPAR),
      activated partial thromboplastin time (APTT), and prothrombin time (PT). Based on
      the hypothesis that CXC sample effects varied with differences in components, we
      performed grey relational analysis (GRA), principal component analysis (PCA),
      ridge regression (RR), and radial basis function (RBF) to evaluate the
      contribution of each identified component. Our results indicate that panaxytriol,
      ginsenoside Rb1, angoroside C, protocatechualdehyde, ginsenoside Rd, and
      calycosin-7-O-beta-D-glucoside are the core bioactive components, and that they
      might play different roles in the alleviation of circulation dysfunction.
      Panaxytriol and ginsenoside Rb1 had close relevance to red blood cell (RBC)
      aggregation, angoroside C was related to platelet aggregation,
      protocatechualdehyde was involved in intrinsic clotting activity, ginsenoside Rd
      affected RBC deformability and plasma proteins, and calycosin-7-O-beta-D
      glucoside influenced extrinsic clotting activity. This study indicates that
      angoroside C, calycosin-7-O-beta-D-glucoside, panaxytriol, and
      protocatechualdehyde may have novel therapeutic uses. 

PMID- 25396726
TI  - Finding needles in a haystack: application of network analysis and target
      enrichment studies for the identification of potential anti-diabetic
      phytochemicals.
AB  - Diabetes mellitus is a debilitating metabolic disorder and remains a significant
      threat to public health. Herbal medicines have been proven to be effective anti
      diabetic agents compared to synthetic drugs in terms of side effects. However,
      the complexity in their chemical constituents and mechanism of action, hinder the
      effort to discover novel anti-diabetic drugs. Hence, understanding the biological
      and chemical basis of pharmacological action of phytochemicals is essential for
      the discovery of potential anti-diabetic drugs. Identifying important active
      compounds, their protein targets and the pathways involved in diabetes would
      serve this purpose. In this context, the present study was aimed at exploring the
      mechanism of action of anti-diabetic plants phytochemicals through network and
      chemical-based approaches. This study also involves a focused and constructive
      strategy for preparing new effective anti-diabetic formulations. Further, a
      protocol for target enrichment was proposed, to identify novel protein targets
      for important active compounds. Therefore, the successive use of network analysis
      combined with target enrichment studies would accelerate the discovery of
      potential anti-diabetic phytochemicals. 

PMID- 25396727
TI  - Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and
      metastasis in human breast cancer by up-regulating miR-34a.
AB  - Diallyl disulfide (DADS) is one of the major volatile components of garlic oil.
      DADS has various biological properties, including anticancer, antiangiogenic, and
      antioxidant effects. However, the anticancer mechanisms of DADS in human breast
      cancer have not been elucidated, particularly in vivo. In this study, we
      demonstrated that the expression of miR-34a was up-regulated in DADS-treated MDA
      MB-231 cells. miR-34a not only inhibited breast cancer growth but also enhanced
      the antitumor effect of DADS, both in vitro and in vivo. Furthermore, Src was
      identified as a target of miR-34a, with miR-34a inhibiting SRC expression and
      consequently triggering the suppression of the SRC/Ras/ERK pathway. These results
      suggest that DADS could be a promising anticancer agent for breast cancer. miR
      34a may also demonstrate a potential gene therapy agent that could enhance the
      antitumor effects of DADS. 

PMID- 25396728
TI  - Protein isotope effects in dihydrofolate reductase from Geobacillus
      stearothermophilus show entropic-enthalpic compensatory effects on the rate
      constant.
AB  - Catalysis by dihydrofolate reductase from the moderately thermophilic bacterium
      Geobacillus stearothermophilus (BsDHFR) was investigated by isotope substitution
      of the enzyme. The enzyme kinetic isotope effect for hydride transfer was close
      to unity at physiological temperatures but increased with decreasing temperatures
      to a value of 1.65 at 5  degrees C. This behavior is opposite to that observed
      for DHFR from Escherichia coli (EcDHFR), where the enzyme kinetic isotope effect
      increased slightly with increasing temperature. These experimental results were
      reproduced in the framework of variational transition-state theory that includes
      a dynamical recrossing coefficient that varies with the mass of the protein. Our
      simulations indicate that BsDHFR has greater flexibility than EcDHFR on the ps-ns
      time scale, which affects the coupling of the environmental motions of the
      protein to the chemical coordinate and consequently to the recrossing
      trajectories on the reaction barrier. The intensity of the dynamic coupling in
      DHFRs is influenced by compensatory temperature-dependent factors, namely the
      enthalpic barrier needed to achieve an ideal transition-state configuration with
      minimal nonproductive trajectories and the protein disorder that disrupts the
      electrostatic preorganization required to stabilize the transition state.
      Together with our previous studies of other DHFRs, the results presented here
      provide a general explanation why protein dynamic effects vary between enzymes.
      Our theoretical treatment demonstrates that these effects can be satisfactorily
      reproduced by including a transmission coefficient in the rate constant
      calculation, whose dependence on temperature is affected by the protein
      flexibility. 

PMID- 25396730
TI  - One-pot sequential alkynylation and cycloaddition: regioselective construction
      and biological evaluation of novel benzoxazole-triazole derivatives.
AB  - Individually, benzoxazole and triazole moieties are of significant biological
      interest owing to their importance in drugs and pharmaceuticals. To assess their
      combined biological impact when woven into one molecule, we designed a novel,
      regioselective, multicomponent, one-pot (MCOP) approach for the construction of
      benzoxazole-linked triazoles. The synthesis has been achieved in two sequential
      steps involving copper-catalyzed alkynylation of benzoxazole followed by a 1,3
      dipolar cycloaddition reaction. By combination of these two bioactive units into
      one core, a series of new benzoxazole-triazole scaffolds has been synthesized and
      subjected to in vitro antibacterial and anticancer evaluation. Tests against
      clinical isolates of Staphylococcus aureus and Escherichia coli showed potent
      Gram-negative activity for compounds 4{1,1,1}, 4{1,1,4}, and 4{1,2,1}. The
      cytotoxicity of the synthesized library was determined against three cancer cell
      lines: HeLa, SKBr3, and Hep G2. Compound 4{2,2,2} showed significant cytotoxicity
      against all the cell lines. These preliminary bioassay evaluations strongly
      suggest the promise and scope of these novel molecules as therapeutic agents in
      medical science. 

PMID- 25396729
TI  - Of 'disgrace' and 'pain'--corticolimbic interaction patterns for disorder
      relevant and emotional words in social phobia.
AB  - Limbic hyperactivation and an impaired functional interplay between the amygdala
      and the prefrontal cortex are discussed to go along with, or even cause,
      pathological anxiety. Within the multi-faceted group of anxiety disorders, the
      highly prevalent social phobia (SP) is characterized by excessive fear of being
      negatively evaluated. Although there is widespread evidence for amygdala
      hypersensitivity to emotional faces in SP, verbal material has rarely been used
      in imaging studies, in particular with an eye on disorder-specificity. Using
      functional magnetic resonance imaging (fMRI) and a block design consisting of (1)
      overall negative, (2) social-phobia related, (3) positive, and (4) neutral words,
      we studied 25 female patients with social phobia and 25 healthy female control
      subjects (HC). Results demonstrated amygdala hyperactivation to disorder-relevant
      but not to generally negative words in SP patients, with a positive correlation
      to symptom severity. A functional connectivity analysis revealed a weaker
      coupling between the amygdala and the left middle frontal gyrus in patients.
      Symptom severity was negatively related to connectivity strength between the
      amygdala and the ventromedial prefrontal and orbitofrontal cortex (Brodmann Area
      10 and 11). The findings clearly support the view of a hypersensitive threat
      detection system, combined with disorder-related alterations in amygdala
      prefrontal cortex connectivity in pathological anxiety. 

PMID- 25396731
TI  - Loss of EP2 receptor subtype in colonic cells compromise epithelial barrier
      integrity by altering claudin-4.
AB  - Prostaglandin E2 (PGE2) is a bioactive lipid mediator that exerts its biological
      function through interaction with four different subtypes of E-Prostanoid
      receptor namely EP1, EP2, EP3 and EP4. It has been known that EP2 receptor is
      differentially over-expressed in the epithelia of inflamed human colonic mucosa.
      However, the significance of the differential expression in altering epithelial
      barrier function is not known. In this study, we used Caco-2 cells expressing EP2
      receptor, either high (EP2S) or low (EP2A), as a model epithelia and determined
      the barrier function of these cell monolayers by measuring the trans epithelial
      resistance (TER). Basal TER of EP2A (but not EP2S) monolayer was significantly
      lower suggesting a loss of colonic epithelial barrier integrity. In comparison,
      the TER of wild type Caco-2 was decreased in response to an EP2 receptor specific
      antagonist (AH-6809) indicating an important role for EP2 receptor in the
      maintenance of epithelial barrier function. The decrease TER in EP2A monolayer
      corresponded with a significant loss of the tight junction (TJ) protein claudin-4
      without affecting other major TJ proteins. Similarly, EP2 receptor
      antagonism/siRNA based silencing significantly decreased claudin-4 expression in
      EP2S cells. Surprisingly, alteration in claudin-4 was not transcriptionally
      regulated in EP2A cells but rather undergoes increased proteosomal degradation.
      Moreover, among the TER compromising cytokines examined (IL-8, IL-1beta, TNF
      alpha, IFN-gamma) only IFN-gamma was significantly up regulated in EP2A cells.
      However, IFN-gamma did not significantly decreased claudin-4 expression in Caco-2
      cells indicating no role for IFN-gamma in degrading claudin-4. We conclude that
      differential down-regulation of EP2 receptor play a major role in compromising
      colonic epithelial barrier function by selectively increasing proteosomal
      degradation of claudin-4. 

PMID- 25396732
TI  - Using manipulated photographs to identify features of streetscapes that may
      encourage older adults to walk for transport.
AB  - Experimental evidence of environmental features important for physical activity
      is challenging to procure in real world settings. The current study aimed to
      investigate the causal effects of environmental modifications on a photographed
      street's appeal for older adults' walking for transport. Secondly, we examined
      whether these effects differed according to gender, functional limitations, and
      current level of walking for transport. Thirdly, we examined whether different
      environmental modifications interacted with each other. Qualitative responses
      were also reported to gain deeper insight into the observed quantitative
      relationships. Two sets of 16 panoramic photographs of a streetscape were
      created, in which six environmental factors were manipulated (sidewalk evenness,
      traffic level, general upkeep, vegetation, separation from traffic, and benches).
      Sixty older adults sorted these photographs on appeal for walking for transport
      on a 7-point scale and reported qualitative information on the reasons for their
      rankings. Sidewalk evenness appeared to have the strongest influence on a
      street's appeal for transport-related walking. The effect of sidewalk evenness
      was even stronger when the street's overall upkeep was good and when traffic was
      absent. Absence of traffic, presence of vegetation, and separation from traffic
      also increased a street's appeal for walking for transport. There were no
      moderating effects by gender or functional limitations. The presence of benches
      increased the streetscape's appeal among participants who already walked for
      transport at least an hour/week. The protocols and methods used in the current
      study carry the potential to further our understanding of environment-PA
      relationships. Our findings indicated sidewalk evenness as the most important
      environmental factor influencing a street's appeal for walking for transport
      among older adults. However, future research in larger samples and in real-life
      settings is needed to confirm current findings. 

PMID- 25396733
TI  - An experimental test of whether the defensive phenotype of an aphid facultative
      symbiont can respond to selection within a host lineage.
AB  - An experiment was conducted to test whether parasitoid resistance within a single
      clonal line of pea aphid (Acyrthosiphon pisum) might increase after exposure to
      the parasitoid wasp Aphidius ervi. Any change in resistance was expected to occur
      through an increase in the density of protective symbiotic bacteria rather than
      genetic change within the aphid or the bacterial symbiont. Six aphid lineages
      were exposed to high parasitoid attack rates over nine generations, each line
      being propagated from individuals that had survived attack; a further six
      lineages were maintained without parasitoids as a control. At the end of the
      experiment the strength of resistance of aphids from treatment and control lines
      were compared. No differences in resistance were found. 

PMID- 25396734
TI  - Comprehensive analysis of the association of EGFR, CALM3 and SMARCD1 gene
      polymorphisms with BMD in Caucasian women.
AB  - SUMMARY: Three genes, including EGFR (epidermal growth factor receptor), CALM3
      (calmodulin 3, calcium-modulated protein 3) and SMARCD1 (SWI/SNF-related matrix
      associated actin-dependent regulator of chromatin subfamily d member 1), play
      different roles in bone and/or fat metabolism in Caucasian women. In this
      population-based investigation of 870 unrelated postmenopausal Caucasian women,
      CALM3 polymorphisms were significantly associated with femoral neck bone mineral
      density (FNK BMD), hip BMD and spine BMD. Age and tobacco status also affected
      BMD levels and were therefore corrected for in our statistical analysis.
      INTRODUCTION: EGFR, CALM3 and SMARCD1 play roles in bone and/or fat metabolism.
      However, the correlations between the polymorphisms of these three genes and body
      composition levels, including BMD, remain to be determined. MATERIALS AND
      METHODS: A population-based investigation of 870 white women was conducted. Forty
      four SNPs (single nucleotide polymorphisms) in EGFR, CALM3 and SMARCD1 were
      chosen by the software, including those of potential functional importance. The
      candidate SNPs were genotyped by the KASPar assay for an association analysis
      with body composition levels. The correlation analysis was assessed by the
      Pearson's product-moment correlation coefficient and Spearman rank-order
      correlation tests, and the family-wise error was corrected using the Wald test
      implemented in PLINK. RESULTS: The SNP rs12461917 in the 3'-flanking region of
      the CALM3 gene was significantly associated with FNK BMD (P = 0.001), hip BMD
      (P<0.001) and spine BMD (P = 0.001); rs11083838 in the 5'-flanking region of
      CALM3 gene was associated with spine BMD (P = 0.009). After adjusting for
      multiple comparisons, rs12461917 remained significant (P-adjusted = 0.033 for FNK
      BMD, P-adjusted = 0.006 for hip BMD and P-adjusted = 0.018 for spine BMD).
      CONCLUSIONS: Our data show that polymorphisms of the CALM3 gene in Caucasian
      women may contribute to variations in the BMD of the hip, spine and femoral neck.

PMID- 25396735
TI  - Hypoxia-inducible factors modulate the stemness and malignancy of colon cancer
      cells by playing opposite roles in canonical Wnt signaling.
AB  - This study examined the role played by hypoxia-inducible factors (HIFs) in
      malignant phenotype maintenance and canonical Wnt signaling. Under normoxia, we
      determined that both HIF-1alpha and HIF-2alpha are expressed in human colon
      cancer cells but not in their non-malignant counterparts. The stable knockdown of
      HIF-1alpha or HIF-2alpha expression induced negative effects on the malignant
      phenotype of colon cancer cells, with lactate production, the rate of apoptosis,
      migration, CXCR4-mediated chemotaxis, and tumorigenic activity all being
      significantly affected by HIF knockdown and with HIF-1alpha depletion exerting
      greater effects. Knockdown of these two HIF transcripts induced different and
      even opposite effects on beta-catenin transcriptional activity in colon cancer
      cells with different genetic Wnt signaling pathways. In SW480 cells, HIF-2alpha
      knockdown did not affect beta-catenin levels, increasing the transcriptional
      activity of beta-catenin by inducing its nuclear accumulation, whereas HIF-1alpha
      silencing negatively affected the stability and transcriptional activity of beta
      catenin, inducing its exit from the nuclei and its recruitment to the cell
      membrane by E-cadherin. In addition, although HIF-1alpha depletion induced a
      reversal of the epithelial-to-mesenchymal transition (EMT), HIF-2alpha silencing
      altered the expression of the stem cell markers CD44, Oct4, and CD24 and of the
      differentiation marker CK20 in the opposite direction as HIF-1alpha silencing.
      Remarkably, HIF-2alpha knockdown also enhanced beta-catenin transcriptional
      activity under hypoxia in cells that displayed normal Wnt signaling, suggesting
      that the gene negatively modulates canonical Wnt signaling in colon cancer cells.
      Taken together, our results indicate that HIFs play opposing roles in canonical
      Wnt signaling and are essential for the stemness and malignancy maintenance of
      colon cancer cells. 

PMID- 25396736
TI  - Stress and resilience in functional somatic syndromes--a structural equation
      modeling approach.
AB  - BACKGROUND: Stress has been suggested to play a role in the development and
      perpetuation of functional somatic syndromes. The mechanisms of how this might
      occur are not clear. PURPOSE: We propose a multi-dimensional stress model which
      posits that childhood trauma increases adult stress reactivity (i.e., an
      individual's tendency to respond strongly to stressors) and reduces resilience
      (e.g., the belief in one's competence). This in turn facilitates the
      manifestation of functional somatic syndromes via chronic stress. We tested this
      model cross-sectionally and prospectively. METHODS: Young adults participated in
      a web survey at two time points. Structural equation modeling was used to test
      our model. The final sample consisted of 3'054 participants, and 429 of these
      participated in the follow-up survey. RESULTS: Our proposed model fit the data in
      the cross-sectional (chi2(21)  = 48.808, p<.001, CFI  = .995, TLI  = .992, RMSEA 
      = .021, 90% CI [.013.029]) and prospective analyses (chi2(21)  =  32.675, p<.05,
      CFI  = .982, TLI  = .969, RMSEA  = .036, 90% CI [.001.059]). DISCUSSION: Our
      findings have several clinical implications, suggesting a role for stress
      management training in the prevention and treatment of functional somatic
      syndromes.

PMID- 25396737
TI  - Lactobacillus casei-01 facilitates the ameliorative effects of proanthocyanidins
      extracted from lotus seedpod on learning and memory impairment in scopolamine
      induced amnesia mice.
AB  - Learning and memory abilities are associated with alterations in gut function.
      The two-way proanthocyanidins-microbiota interaction in vivo enhances the
      physiological activities of proanthocyanidins and promotes the regulation of gut
      function. Proanthocyanidins extracted from lotus seedpod (LSPC) have shown the
      memory-enhancing ability. However, there has been no literature about whether
      Lactobacillus casei-01 (LC) enhances the ameliorative effects of LSPC on learning
      and memory abilities. In this study, learning and memory abilities of scopolamine
      induced amnesia mice were evaluated by Y-maze test after 20-day administration of
      LC (10(9) cfu/kg body weight (BW)), LSPC (low dose was 60 mg/kg BW (L-LSPC) and
      high dose was 90 mg/kg BW (H-LSPC)), or LSPC and LC combinations (L-LSPC+LC and H
      LSPC+LC). Alterations in antioxidant defense ability and oxidative damage of
      brain, serum and colon, and brain cholinergic system were investigated as the
      possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced
      by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC
      and LC combinations ameliorated scopolamine-induced memory impairment by
      improving total antioxidant capacity (TAOC) level, glutathione peroxidase (GSH
      Px) and total superoxide dismutase (T-SOD) activities of brain, serum and colon,
      suppressing malondialdehyde (MDA) level of brain, serum and colon, and inhibiting
      brain acetylcholinesterase (AchE), myeloperoxidase, total nitric oxide synthase
      and neural nitric oxide synthase (nNOS) activities, and nNOS mRNA level.
      Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of
      colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum,
      and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level
      and AchE activity. These results indicated that LC promoted the memory-enhancing
      effect of LSPC in scopolamine-induced amnesia mice.

PMID- 25396738
TI  - Molecular approaches to chromatography using single molecule spectroscopy.

PMID- 25396739
TI  - Potential conservation of circadian clock proteins in the phylum Nematoda as
      revealed by bioinformatic searches.
AB  - Although several circadian rhythms have been described in C. elegans, its
      molecular clock remains elusive. In this work we employed a novel bioinformatic
      approach, applying probabilistic methodologies, to search for circadian clock
      proteins of several of the best studied circadian model organisms of different
      taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis
      thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other
      members of the phylum Nematoda. With this approach we found that the Nematoda
      contain proteins most related to the core and accessory proteins of the insect
      and mammalian clocks, which provide new insights into the nematode clock and the
      evolution of the circadian system. 

PMID- 25396743
TI  - Methanol from CO2 by organo-cocatalysis: CO2 capture and hydrogenation in one
      process step.
AB  - Carbon dioxide chemically bound to alcohol-amines was hydrogenated to methanol
      under retrieval of these industrially used CO2 capturing reagents. The energetics
      of the process can be seen as a partial cancellation of the exothermic heat of
      reaction of the hydrogenation with the endothermic one of the CO2 release from
      the capturing reagent. The process provides a means to significantly improve the
      energy efficiency of CO2 to methanol conversions. 

PMID- 25396741
TI  - Detection theory in identification of RNA-DNA sequence differences using RNA
      sequencing.
AB  - Advances in sequencing technology have allowed for detailed analyses of the
      transcriptome at single-nucleotide resolution, facilitating the study of RNA
      editing or sequence differences between RNA and DNA genome-wide. In humans, two
      types of post-transcriptional RNA editing processes are known to occur: A-to-I
      deamination by ADAR and C-to-U deamination by APOBEC1. In addition to these
      sequence differences, researchers have reported the existence of all 12 types of
      RNA-DNA sequence differences (RDDs); however, the validity of these claims is
      debated, as many studies claim that technical artifacts account for the majority
      of these non-canonical sequence differences. In this study, we used a detection
      theory approach to evaluate the performance of RNA-Sequencing (RNA-Seq) and
      associated aligners in accurately identifying RNA-DNA sequence differences. By
      generating simulated RNA-Seq datasets containing RDDs, we assessed the effect of
      alignment artifacts and sequencing error on the sensitivity and false discovery
      rate of RDD detection. Overall, we found that even in the presence of sequencing
      errors, false negative and false discovery rates of RDD detection can be
      contained below 10% with relatively lenient thresholds. We also assessed the
      ability of various filters to target false positive RDDs and found them to be
      effective in discriminating between true and false positives. Lastly, we used the
      optimal thresholds we identified from our simulated analyses to identify RDDs in
      a human lymphoblastoid cell line. We found approximately 6,000 RDDs, the majority
      of which are A-to-G edits and likely to be mediated by ADAR. Moreover, we found
      the majority of non A-to-G RDDs to be associated with poorer alignments and
      conclude from these results that the evidence for widespread non-canonical RDDs
      in humans is weak. Overall, we found RNA-Seq to be a powerful technique for
      surveying RDDs genome-wide when coupled with the appropriate thresholds and
      filters. 

PMID- 25396742
TI  - Establishment of tools for neurogenetic analysis of sexual behavior in the
      silkmoth, Bombyx mori.
AB  - BACKGROUND: Silkmoth, Bombyx mori, is an ideal model insect for investigating the
      neural mechanisms underlying sex pheromone-induced innate behavior. Although
      transgenic techniques and the GAL4/UAS system are well established in the
      silkmoth, genetic tools useful for investigating brain function at the neural
      circuit level have been lacking. RESULTS: In the present study, we established
      silkmoth strains in which we could visualize neural projections (UAS-mCD8GFP) and
      cell nucleus positions (UAS-GFP.nls), and manipulate neural excitability by
      thermal stimulation (UAS-dTrpA1). In these strains, neural projections and
      nucleus position were reliably labeled with green fluorescent protein in a GAL4
      dependent manner. Further, the behavior of silkworm larvae and adults could be
      controlled by GAL4-dependent misexpression of dTrpA1. Ubiquitous dTrpA1
      misexpression led both silkmoth larvae and adults to exhibit seizure-like
      phenotypes in a heat stimulation-dependent manner. Furthermore, dTrpA1
      misexpression in the sex pheromone receptor neurons of male silkmoths allowed us
      to control male sexual behavior by changing the temperature. Thermally stimulated
      male silkmoths exhibited full sexual behavior, including wing-flapping,
      orientation, and attempted copulation, and precisely approached a thermal source
      in a manner similar to male silkmoths stimulated with the sex pheromone.
      CONCLUSION: These findings indicate that a thermogenetic approach using dTrpA1 is
      feasible in Lepidopteran insects and thermogenetic analysis of innate behavior is
      applicable in the silkmoth. These tools are essential for elucidating the
      relationships between neural circuits and function using neurogenetic methods.

PMID- 25396740
TI  - Grey and white matter correlates of recent and remote autobiographical memory
      retrieval--insights from the dementias.
AB  - The capacity to remember self-referential past events relies on the integrity of
      a distributed neural network. Controversy exists, however, regarding the
      involvement of specific brain structures for the retrieval of recently
      experienced versus more distant events. Here, we explored how characteristic
      patterns of atrophy in neurodegenerative disorders differentially disrupt remote
      versus recent autobiographical memory. Eleven behavioural-variant frontotemporal
      dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy
      older Controls completed the Autobiographical Interview. All patient groups
      displayed significant remote memory impairments relative to Controls. Similarly,
      recent period retrieval was significantly compromised in behavioural-variant
      frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients
      scored in line with Controls. Voxel-based morphometry and diffusion tensor
      imaging analyses, for all participants combined, were conducted to investigate
      grey and white matter correlates of remote and recent autobiographical memory
      retrieval. Neural correlates common to both recent and remote time periods were
      identified, including the hippocampus, medial prefrontal, and frontopolar
      cortices, and the forceps minor and left hippocampal portion of the cingulum
      bundle. Regions exclusively implicated in each time period were also identified.
      The integrity of the anterior temporal cortices was related to the retrieval of
      remote memories, whereas the posterior cingulate cortex emerged as a structure
      significantly associated with recent autobiographical memory retrieval. This
      study represents the first investigation of the grey and white matter correlates
      of remote and recent autobiographical memory retrieval in neurodegenerative
      disorders. Our findings demonstrate the importance of core brain structures,
      including the medial prefrontal cortex and hippocampus, irrespective of time
      period, and point towards the contribution of discrete regions in mediating
      successful retrieval of distant versus recently experienced events. 

PMID- 25396744
TI  - Pressure-Sensitive Adhesives under the Influence of Relative Humidity: Inner
      Structure and Failure Mechanisms.
AB  - Model pressure-sensitive adhesive (PSA) films of the statistical copolymer P(EHA
      stat-20MMA), which comprises 80% ethylhexyl acrylate (EHA) and 20% methyl
      methacrylate (MMA), are studied. The PSA films are stored under different
      relative humidities from <2% to 96% for 24 h and subsequently investigated
      concerning the near-surface composition profile by measuring X-ray reflectivity
      (XRR) and tack performance. For both types of measurements, special custom-made
      sample environments are used, which ensure constant temperature and relative
      humidity during the XRR and tack measurements. Different failure mechanisms of
      the adhesive bond are found by adjusting the relative humidity. XRR measurements
      evidence enrichment layers in vicinity to and at the surface depending on the
      provided relative humidity during the postproduction treatment, which also
      influence the tack performance. This finding is supported by tack measurements
      using punches with different roughness. 

PMID- 25396745
TI  - Characterization of a spontaneous novel mutation in the NPC2 gene in a cat
      affected by Niemann Pick type C disease.
AB  - Niemann-Pick C disease (NPC) is an autosomal recessive lysosomal storage disorder
      characterized by accumulation of unesterified cholesterol and other lipids within
      the lysosomes due to mutation in NPC1 or NPC2 genes. A feline model of NPC
      carrying a mutation in NPC1 gene has been previously described. We have
      identified two kittens affected by NPC disease due to a mutation in NPC2 gene.
      They manifested with tremors at the age of 3 months, which progressed to dystonia
      and severe ataxia. At 6 months of age cat 2 was unable to stand without
      assistance and had bilaterally reduced menace response. It died at the age of 10
      months. Post-mortem histological analysis of the brain showed the presence of
      neurons with cytoplasmic swelling and vacuoles, gliosis of the substantia nigra
      and degeneration of the white matter. Spheroids with accumulation of
      ubiquitinated aggregates were prominent in the cerebellar cortex. Purkinje cells
      were markedly reduced in number and they showed prominent intracytoplasmic
      storage. Scattered perivascular aggregates of lymphocytes and microglial cells
      proliferation were present in the thalamus and midbrain. Proliferation of
      Bergmann glia was also observed. In the liver, hepatocytes were swollen because
      of accumulation of small vacuoles and foamy Kupffer cells were also detected.
      Foamy macrophages were observed within the pulmonary interstitium and alveoli as
      well. At 9 months cat 1 was unable to walk, developed seizures and it was
      euthanized at 21 months. Filipin staining of cultured fibroblasts showed massive
      storage of unesterified cholesterol. Molecular analysis of NPC1 and NPC2 genes
      showed the presence of a homozygous intronic mutation (c.82+5G>A) in the NPC2
      gene. The subsequent analysis of the mRNA showed that the mutation causes the
      retention of 105 bp in the mature mRNA, which leads to the in frame insertion of
      35 amino acids between residues 28 and 29 of NPC2 protein (p.G28_S29ins35). 

PMID- 25396747
TI  - Rhodium-catalyzed oxidative annulation of hydrazines with alkynes using a
      nitrobenzene oxidant.
AB  - Rhodium-catalyzed oxidative annulation of hydrazines with alkynes has been
      accomplished using 1,3-dinitrobenzene as an oxidant. A variety of hydrazines with
      alkynes were converted to 1-aminoindole derivatives in good to high yields.
      Mechanistic investigations support the idea that 1,3-dinitrobenzene serves as the
      oxidant during C-H activation. This is, to our knowledge, the first report of a
      nitrobenzene compound used as the oxidant in transition-metal-catalyzed C-H
      activation. 

PMID- 25396746
TI  - The Arabidopsis PLAT domain protein1 is critically involved in abiotic stress
      tolerance.
AB  - Despite the completion of the Arabidopsis genome sequence, for only a relatively
      low percentage of the encoded proteins experimental evidence concerning their
      function is available. Plant proteins that harbour a single PLAT (Polycystin,
      Lipoxygenase, Alpha-toxin and Triacylglycerol lipase) domain and belong to the
      PLAT-plant-stress protein family are ubiquitously present in monocot and dicots.
      However, the function of PLAT-plant-stress proteins is still poorly understood.
      Therefore, we have assessed the function of the uncharacterised Arabidopsis PLAT
      plant-stress family members through a combination of functional genetic and
      physiological approaches. PLAT1 overexpression conferred increased abiotic stress
      tolerance, including cold, drought and salt stress, while loss-of-function
      resulted in opposite effects on abiotic stress tolerance. Strikingly, PLAT1
      promoted growth under non-stressed conditions. Abiotic stress treatments induced
      PLAT1 expression and caused expansion of its expression domain. The ABF/ABRE
      transcription factors, which are positive mediators of abscisic acid signalling,
      activate PLAT1 promoter activity in transactivation assays and directly bind to
      the ABRE elements located in this promoter in electrophoretic mobility shift
      assays. This suggests that PLAT1 represents a novel downstream target of the
      abscisic acid signalling pathway. Thus, we showed that PLAT1 critically functions
      as positive regulator of abiotic stress tolerance, but also is involved in
      regulating plant growth, and thereby assigned a function to this previously
      uncharacterised PLAT domain protein. The functional data obtained for PLAT1
      support that PLAT-plant-stress proteins in general could be promising targets for
      improving abiotic stress tolerance without yield penalty. 

PMID- 25396749
TI  - The critical conditions for coalescence in phase field simulations of colliding
      droplets in shear.
AB  - Simulations have been performed using the free-energy binary-liquid lattice
      Boltzmann method with sufficient resolution that the critical capillary number
      for coalescence was determined for collisions between droplets in simple shear
      with a small initial offset in the shear gradient direction. The simulations were
      used to study the behavior of the interacting interfaces and the film between
      them during collisions over a wide range of capillary numbers with emphasis on
      near-critical conditions. From these three-dimensional simulations with deforming
      interfaces, several features of the evolution of the film between the drops were
      observed. The critical film thickness was determined to be similar to the
      interface thickness, a power law described the dependence of the minimum film
      thickness on the capillary number in collisions without coalescece, and an
      inflection point was found in the dynamics of the minimum distance between drops
      that eventually coalesce. The rotation of the film and the flow in it were also
      studied, and a reversal in the flow was found to occur before coalescence. The
      mobility of the phase field was therefore important in the continued thinning of
      the film at the points of minimum thickness after the flow reversal. A comparison
      of the critical capillary number and critical film thickness in the simulations
      with the values for experiments in confined simple shear indicated that the
      effective physical radius of the simulated droplets was on the order of several
      micrometers. The results are significant for simulations of droplet interactions
      and emulsion flows in complex geometries and turbulence because they demonstrate
      the necessary scale of the computations and how parameters, such as the interface
      thickness and phase field mobility, should be selected for accurate results. 

PMID- 25396748
TI  - Nematic director reorientation at solid and liquid interfaces under flow: SAXS
      studies in a microfluidic device.
AB  - In this work we investigate the interplay between flow and boundary condition
      effects on the orientation field of a thermotropic nematic liquid crystal under
      flow and confinement in a microfluidic device. Two types of experiments were
      performed using synchrotron small-angle X-ray-scattering (SAXS). In the first, a
      nematic liquid crystal flows through a square-channel cross section at varying
      flow rates, while the nematic director orientation projected onto the
      velocity/velocity gradient plane is measured using a 2D detector. At moderate-to
      high flow rates, the nematic director is predominantly aligned in the flow
      direction, but with a small tilt angle of ~+/-11 degrees  in the velocity
      gradient direction. The director tilt angle is constant throughout most of the
      channel width but switches sign when crossing the center of the channel, in
      agreement with the Ericksen-Leslie-Parodi (ELP) theory. At low flow rates,
      boundary conditions begin to dominate, and a flow profile resembling the escaped
      radial director configuration is observed, where the director is seen to vary
      more smoothly from the edges (with homeotropic alignment) to the center of the
      channel. In the second experiment, hydrodynamic focusing is employed to confine
      the nematic phase into a sheet of liquid sandwiched between two layers of Triton
      X-100 aqueous solutions. The average nematic director orientation shifts to some
      extent from the flow direction toward the liquid boundaries, although it remains
      unclear if one tilt angle is dominant through most of the nematic sheet (with
      abrupt jumps near the boundaries) or if the tilt angle varies smoothly between
      two extreme values (~90 and 0 degrees ). The technique presented here could be
      applied to perform high-throughput measurements for assessing the influence of
      different surfactants on the orientation of nematic phases and may lead to
      further improvements in areas such as boundary lubrication and clarifying the
      nature of defect structures in LC displays. 

PMID- 25396750
TI  - ZnO anchored on vertically aligned graphene: binder-free anode materials for
      lithium-ion batteries.
AB  - ZnO has been regarded as a promising anode material for the next-generation
      lithium-ion battery. Unfortunately, the structure broken caused by the volume
      change of ZnO and the capacity degression due to the irreversible electrochemical
      reaction of ZnO still remain two major challenges. Here, we design a novel kind
      of in situ growth binder-free ZnO-based anodes via ZnO anchored on vertically
      aligned graphene. The composite anode retains physical integrity post cycling.
      Especially, the good conductivity of graphene and the ultrasmall size of ZnO
      particles help to produce a completely reversible electrochemical reaction of ZnO
      based anode. The composite material exhibits a high capacity (810 mAh g(-1)),
      long cycle life, good cycle stability, and fast charge/discharge rate.

PMID- 25396751
TI  - From dissipative dynamics to studies of heat transfer at the nanoscale: analysis
      of the spin-boson model.
AB  - We study in a unified manner the dissipative dynamics and the transfer of heat in
      the two-bath spin-boson model. We use the Bloch-Redfield (BR) formalism, valid in
      the very weak system-bath coupling limit, the noninteracting-blip approximation
      (NIBA), applicable in the nonadiabatic limit, and iterative, numerically exact
      path integral tools. These methodologies were originally developed for the
      description of the dissipative dynamics of a quantum system, and here they are
      applied to explore the problem of quantum energy transport in a nonequilibrium
      setting. Specifically, we study the weak-to-intermediate system-bath coupling
      regime at high temperatures kBT/h > epsilon, with epsilon as the characteristic
      frequency of the two-state system. The BR formalism and NIBA can lead to close
      results for the dynamics of the reduced density matrix (RDM) in a certain range
      of parameters. However, relatively small deviations in the RDM dynamics propagate
      into significant qualitative discrepancies in the transport behavior. Similarly,
      beyond the strict nonadiabatic limit NIBA's prediction for the heat current is
      qualitatively incorrect: It fails to capture the turnover behavior of the current
      with tunneling energy and temperature. Thus, techniques that proved meaningful
      for describing the RDM dynamics, to some extent even beyond their rigorous range
      of validity, should be used with great caution in heat transfer calculations,
      because qualitative-serious failures develop once parameters are mildly stretched
      beyond the techniques' working assumptions.

PMID- 25396752
TI  - Nature of holes, oxidation states, and hypervalency in covellite (CuS).
AB  - The electronic structure of covellite (CuS) is analyzed on the basis of density
      functional theory calculations. The nature of holes in the valence band, as well
      as the so far much debated question of the appropriate oxidation formalism for
      this conductor, is discussed. The role of S-S bonds and the anomalous
      coordination of one type of sulfur atom (hypervalency) are considered. It is
      suggested that the low-temperature transition is mostly a symmetry-lowering
      process slightly stabilizing the Cu-S network. 

PMID- 25396753
TI  - Thermodynamic signature of secondary nano-emulsion formation by isothermal
      titration calorimetry.
AB  - The stabilization of oil in water nano-emulsions by means of a polymer coating is
      extremely important; it prolongs the shelf life of the product and makes it
      suitable for a variety of applications ranging from nutraceutics to cosmetics and
      pharmaceutics. To date, an effective methodology to assess the best formulations
      in terms of thermodynamic stability has yet to be designed. Here, we perform a
      complete physicochemical characterization based on isothermal titration
      calorimetry (ITC) compared to conventional dynamic light scattering (DLS) to
      identify polymer concentration domains that are thermodynamically stable and to
      define the degree of stability through thermodynamic functions depending upon any
      relevant parameter affecting the stability itself, such as type of polymer
      coating, droplet distance, etc. For instance, the method was proven by measuring
      the energetics in the case of two different biopolymers, chitosan and poly-L
      lysine, and for different concentrations of the emulsion coated with poly-L
      lysine.

PMID- 25396755
TI  - CE: Original research: the use of surveillance technology in residential
      facilities for people with dementia or intellectual disabilities: a study among
      nurses and support staff.
AB  - BACKGROUND: The use of surveillance technology in residential care facilities for
      people with dementia or intellectual disabilities is often promoted both as a
      solution to understaffing and as a means to increasing clients' autonomy. But
      there are fears that such use might attenuate the care relationship. OBJECTIVE:
      To investigate how surveillance technology is actually being used by nurses and
      support staff in residential care facilities for people with dementia or
      intellectual disabilities, in order to explore the possible benefits and
      drawbacks of this technology in practice. METHODS: An ethnographic field study
      was carried out in two residential care facilities: a nursing home for people
      with dementia and a facility for people with intellectual disabilities. Data were
      collected through field observations and informal conversations as well as
      through formal interviews. RESULTS: Five overarching themes on the use of
      surveillance technology emerged from the data: continuing to do rounds, alarm
      fatigue, keeping clients in close proximity, locking the doors, and forgetting to
      take certain devices off. Despite the presence of surveillance technology,
      participants still continued their rounds. Alarm fatigue sometimes led
      participants to turn devices off. Though the technology allowed wandering clients
      to be tracked more easily, participants often preferred keeping clients nearby,
      and preferably behind locked doors at night. At times participants forgot to
      remove less visible devices (such as electronic bracelets) when the original
      reason for use expired. CONCLUSIONS: A more nuanced view of the benefits and
      drawbacks of surveillance technology is called for. Study participants tended to
      incorporate surveillance technology into existing care routines and to do so with
      some reluctance and reservation. They also tended to favor certain technologies,
      for example, making intensive use of certain devices (such as digital enhanced
      cordless telecommunications phones) while demonstrating ambivalence about others
      (such as the tagging and tracking systems). Client safety and physical proximity
      seemed to be dominant values, suggesting that the fear that surveillance
      technology will cause attenuation of the care relationship is unfounded. On the
      other hand, the values of client freedom and autonomy seemed less influential;
      participants often appeared unwilling to take risks with the technology. Care
      facilities wishing to implement surveillance technology should encourage ongoing
      dialogue on how staff members view and understand the concepts of autonomy and
      risk. A clear and well-formulated vision for the use of surveillance technology
      one understood and supported by all stakeholders-seems imperative to successful
      implementation.

PMID- 25396754
TI  - The E2F2 transcription factor sustains hepatic glycerophospholipid homeostasis in
      mice.
AB  - Increasing evidence links metabolic signals to cell proliferation, but the
      molecular wiring that connects the two core machineries remains largely unknown.
      E2Fs are master regulators of cellular proliferation. We have recently shown that
      E2F2 activity facilitates the completion of liver regeneration after partial
      hepatectomy (PH) by regulating the expression of genes required for S-phase
      entry. Our study also revealed that E2F2 determines the duration of hepatectomy
      induced hepatic steatosis. A transcriptomic analysis of normal adult liver
      identified "lipid metabolism regulation" as a major E2F2 functional target,
      suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type
      (E2F2+/+) and E2F2 deficient (E2F2-/-) mice to investigate the in vivo role of
      E2F2 in the composition of liver lipids and fatty acids in two metabolically
      different contexts: quiescence and 48-h post-PH, when cellular proliferation and
      anabolic demands are maximal. We show that liver regeneration is accompanied by
      large triglyceride and protein increases without changes in total phospholipids
      both in E2F2+/+ and E2F2-/- mice. Remarkably, we found that the phenotype of
      quiescent liver tissue from E2F2-/- mice resembles the phenotype of proliferating
      E2F2+/+ liver tissue, characterized by a decreased phosphatidylcholine to
      phosphatidylethanolamine ratio and a reprogramming of genes involved in
      generation of choline and ethanolamine derivatives. The diversity of fatty acids
      in total lipid, triglycerides and phospholipids was essentially preserved on E2F2
      loss both in proliferating and non-proliferating liver tissue, although notable
      exceptions in inflammation-related fatty acids of defined phospholipid classes
      were detected. Overall, our results indicate that E2F2 activity sustains the
      hepatic homeostasis of major membrane glycerolipid components while it is
      dispensable for storage glycerolipid balance. 

PMID- 25396756
TI  - CE: The obesity epidemic, part 1: understanding the origins.
AB  - OVERVIEW: The obesity epidemic remains a significant health problem in the United
      States and worldwide, with multiple associated physical and societal costs. To
      contribute to obesity's treatment and prevention, nurses must be conversant in a
      wide range of theoretical and clinical perspectives on the problem. This article,
      the first in a two-part series, defines the terms used in the treatment of
      obesity and outlines pathophysiologic, psychological, and social factors that
      influence weight control. Part 2, which will appear in next month's issue,
      presents a theoretical framework that can be used to guide nursing assessment of
      both patient and family, thereby informing intervention.

PMID- 25396757
TI  - Promoter methylation-mediated silencing of beta-catenin enhances invasiveness of
      non-small cell lung cancer and predicts adverse prognosis.
AB  - beta-Catenin plays dual role in adhesion complex formation and the Wnt signaling
      pathway. Although beta-catenin expression appears to be upregulated and Wnt
      signaling pathway is activated in the majority of cancers, its expression level
      seems to be lost in non-small cell lung cancer (NSCLC). We previously reported
      that the promoter of beta-catenin was hypermethylated in two NSCLC cell lines. In
      the current study, we expanded our analysis for the methylation status of beta
      catenin promoter region and its protein expression in seven NSCLC cell lines and
      a series of 143 cases of primary human lung cancer with adjacent non-neoplastic
      tissues. Quantitative methylation specific PCR (qMSP) analysis showed methylation
      of beta-catenin promoter region in five NSCLC cell lines, with increased beta
      catenin protein levels upon 5'-Aza-2'-deoxycytidine (5-aza-dC) treatment. The
      methylation status in SPC (methylated) and A549 (unmethylated) was confirmed by
      bisulfite sequencing PCR. 5-Aza-dC treatment inhibited invasiveness of SPC but
      not A549. Immunofluorescence analysis showed membranous beta-catenin expression
      was lost in SPC and could be re-established by 5-aza-dC, while Wnt3a treatment
      led to nuclear translocation of beta-catenin in both SPC and A549. Dual
      luciferase assays indicated that 5-aza-dC treatment caused no significant
      increase in Wnt signaling activity compared with Wnt3a treatment. The effect of
      demethylation agent in SPC can be reversed by beta-catenin depletion but not E
      cadherin depletion which indicated that the methylation mediated beta-catenin
      silencing might enhance NSCLC invasion and metastasis in an E-cadherin
      independent manner. Subsequent immunohistochemistry results further confirmed
      that beta-catenin promoter hypermethylation correlated with loss of
      immunoreactive protein expression, positive lymph node metastasis, high TNM stage
      and poor prognosis. The present study implicates beta-catenin promoter
      hypermethylation in the mechanism of epigenetic changes underlying NSCLC
      metastasis and progression, thus indicating the potential of beta-catenin as a
      novel epigenetic target for the treatment of NSCLC patients. 

PMID- 25396758
TI  - Marijuana motivations across adolescence: impacts on use and consequences.
AB  - Background. Motivational models for marijuana use have focused on reasons to use
      marijuana, but rarely consider motives to abstain. OBJECTIVES: We examined how
      both adolescent marijuana abstinence motives and use motives contribute to
      marijuana use and problems at the end of emerging adulthood. Methods. 434
      community recruited youth who had not initiated marijuana use at baseline were
      followed from adolescence (at ages 12, 15, and 18 years) into emerging adulthood
      (age 25 years). Motives to abstain and to use marijuana, marijuana consumption,
      and marijuana-related problems were assessed across time. Results. Endorsing more
      motives to abstain from marijuana across adolescence predicted less marijuana use
      in emerging adulthood and fewer marijuana-related problems when controlling for
      past motives to abstain and marijuana-related behavior. Positive reinforcement
      use motives related to increased marijuana consumption and problems, and negative
      reinforcement motives predicted problems when controlling for past marijuana use
      motives and behaviors. Expansion motives during adolescence related to lower
      marijuana use in emerging adulthood. When considered together, motives to abstain
      buffered the effect of negative reinforcement motives on outcomes at age 25 for
      youth endorsing a greater number of abstinence motives. Conclusions/
      Implications. Given these findings, inclusion of both motives to use and abstain
      is warranted within comprehensive models of marijuana use decision making and may
      provide important markers for prevention and intervention specialists.

PMID- 25396759
TI  - Results of rotational thromboelastometry, coagulation activation markers and
      thrombin generation assays in orthopedic patients during thromboprophylaxis with
      rivaroxaban and enoxaparin: a prospective cohort study.
AB  - BACKGROUND: A prospective observational study was conducted in two clinical
      cohorts of patients to compare the effect of enoxaparin and rivaroxaban on
      rotational thromboelastometry (ROTEM), coagulation activation markers and
      thrombin generation. METHODS: A total of 188 consecutive patients scheduled for
      major orthopedic surgery receiving 40-mg enoxaparin subcutaneously or 10-mg
      rivaroxaban orally were evaluated. Blood samples were taken before induction of
      anesthesia and on day 4 after surgery [postoperative day 4 (pod 4)]. The
      extrinsically (EXTEM) and the intrinsically (INTEM) activated ROTEM assay,
      antithrombin, prothrombin fragments (F1 + 2), thrombin-antithrombin complex (TAT)
      and D-dimers were measured, and the thrombodynamic ratio (TDR) was calculated.
      Thrombin generation was determined using calibrated automated thrombography. To
      compare the groups, changes (Delta) in baseline versus pod 4 were calculated.
      RESULTS: EXTEM clotting time (CT) increased more with rivaroxaban than with
      enoxaparin; values above the reference range were observed (median DeltaEXTEM-CT
      15 vs. 5 s, P <= 0.0001). The increase in INTEM-CT (values remained within the
      normal ranges) was slight with enoxaparin and significant with rivaroxaban;
      DeltaINTEM-CT was comparable. EXTEM-TDR, unchanged with rivaroxaban, increased
      significantly with enoxaparin, whereas DeltaINTEM-TDR was comparable. DeltaAT,
      DeltaF1 + 2 and DeltaTAT were significantly lower in the rivaroxaban group.
      Endogenous thrombin potential (ETP), unchanged with rivaroxaban, decreased
      significantly with enoxaparin; the maximal rising slope (mean velocity rate
      index) decreased more with rivaroxaban. CONCLUSION: Data show that prolonged CT
      in the extrinsic ROTEM and thrombin generation assays reflecting initiation and
      propagation of thrombin may be useful for detecting treatment with rivaroxaban.
      The significance of observed differences in markers of coagulation needs to be
      investigated further.

PMID- 25396760
TI  - The association of elevated mean platelet volume with the outcome of acute
      mesenteric ischemia.
AB  - Mesenteric ischemia is a life-threatening vascular emergency with high mortality
      rates. Mean platelet volume (MPV) has been shown to be closely related to
      platelet activation. We investigated whether MPV was associated with outcome of
      acute mesenteric ischemia (AMI). Sixty-one patients who were operated for AMI
      were retrospectively evaluated. Patients were divided into two groups: survivors
      and nonsurvivors, according to the outcome, and the two groups were compared in
      terms of MPV levels and other prognostic factors. Urea, creatinine, alkaline
      phosphatase, amylase, gamma-glutamyl transferase and MPV levels were
      significantly higher in nonsurvivors, when compared to that of survivors. In
      addition, hypertension, atherosclerotic heart diseases and rhythm disorders were
      statistically significant risk factors for mortality. AMI is an uncommon but
      highly lethal surgical emergency. Our results indicate that an elevated MPV is
      associated with a worse outcome in patients with AMI. 

PMID- 25396761
TI  - Acquired inhibitors to factor VIII and fibrinogen in the setting of T-cell large
      granular lymphocyte leukemia: a case report and review of the literature.
AB  - Large granular lymphocyte (LGL) leukemia is an indolent lymphoproliferative
      malignancy which dysregulates humoral immunity and underlies the myriad
      autoimmune phenomena. We describe a 62-year-old woman with Felty's syndrome who
      developed a severe bleeding diathesis. Laboratory evaluation demonstrated
      acquired inhibitors to both factor VIII (FVIII) and fibrinogen, likely secondary
      to T-cell LGL leukemia. After a complicated course, the patient's inhibitors were
      extinguished with rituximab and high-dose corticosteroids. Bleeding was
      controlled with alternating FEIBA (factor eight inhibitor bypassing activity) and
      recombinant activated FVII. This report reviews the literature comparing the
      efficacy of various treatment modalities for both disorders. To our knowledge,
      this is the first reported case of a patient with LGL leukemia acquiring an
      inhibitor to FVIII or fibrinogen. 

PMID- 25396762
TI  - Effects of gabexate mesilate on coagulopathy and organ dysfunction in rats with
      endotoxemia: a potential use of thrombelastography in endotoxin-induced sepsis.
AB  - Sepsis and its associated multiple organ failure are related to high mortality in
      critical patients. Several studies have reported that gabexate mesilate, a
      synthetic inhibitor of trypsin-like serine protease, protects tissues/organs
      against injury in the models of endotoxemia. The aim of this study was to examine
      whether gabexate mesilate could attenuate coagulopathy and organ dysfunction in
      lipopolysaccharide (LPS)-induced sepsis model by using thrombelastography (TEG).
      LPS (7.5  mg/kg/h, intravenouly for 4  h) was administered to male adult Wistar
      rats. Some of the LPS rats received a continuous infusion of gabexate mesilate
      (10  mg/kg/h, intravenously for 8.5  h) for 30  min before the LPS
      administration. Variable parameters of hemodynamics, biochemistry, hemostasis and
      inflammatory response were measured for 6  h after the LPS infusion. TEG
      variables (R-time, K-time, alpha-angle, and maximal amplitude) were also
      measured. The pretreatment of LPS rats with gabexate mesilate significantly
      attenuated the lung, liver and kidney dysfunction, consumptive coagulopathy, the
      increases in serum tumor necrosis factor-alpha, interleukin-6, plasma thrombin
      antithrombin complex and plasminogen activator inhibitor-1, and neutrophils
      infiltration score in lung, liver and kidney, compared with the LPS alone group.
      In addition, TEG parameters correlated with tissue and liver injury in the late
      phase of endotoxemia. In particular, a strong negative correlation between
      maximal amplitude at 4  h and Ln (lactate dehydrogenase) at 6  h after LPS
      infusion was noted (r = -0.752, P < 0.001, R = 0.566). These results indicate
      that beneficial effects of anticoagulants (e.g. gabexate mesilate) in endotoxemia
      could be monitored by TEG per se.

PMID- 25396763
TI  - Effect of single nucleotide polymorphism in thrombin-activatable fibrinolysis
      inhibitor on the risk of diabetic macrovascular disease.
AB  - Hypofibrinolysis is commonly found in patients with diabetes mellitus and is
      associated with the increased risk for many diabetic complications. An important
      inhibitor of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI),
      participates in hypofibrinolysis in diabetes mellitus and may be involved in
      diabetic macrovascular disease. The present study was designed to determine
      whether TAFI polymorphisms (505G/A and 1040C/T) and TAFI levels are correlated
      with the development of type 2 diabetes mellitus (T2DM) and macrovascular
      diseases (MVDs). A total of 249 clinical samples were collected, including 102
      healthy individuals (H group), 44 T2DM patients without MVD (T group) and 103
      T2DM patients with MVD (M group). The 505G/A polymorphism was equally represented
      in the three groups. In contrast, analysis of the 1040C/T polymorphism revealed a
      statistically lower percentage of the T allele in the M group than in the H group
      (P = 0.014). This difference was due to decreased T/T homozygotes in the M groups
      compared with the H group (P = 0.029). The antigen TAFI level was 31.72 +/-
      13.64% in the H group, 62.56 +/- 18.77% in the T group (P < 0.05, compared with
      the H group) and 63.70 +/- 15.76% in the M group (P < 0.05, compared with the H
      group). As high plasma TAFI level is associated with the increasing risk of T2DM,
      it may thus serve as a potential marker for the diagnosis of T2DM. 

PMID- 25396764
TI  - Rationale for individualizing haemophilia care.
AB  - Owing to the heterogeneity in the clinical phenotype of haemophilia A and B, it
      is now recognized that disease severity (based on factor VIII/IX activity) may no
      longer be the most appropriate guide for treatment and that a 'one-size-fits-all'
      approach is unlikely to achieve optimal therapy. Based on the present literature
      and consensus views of a group of experts in the field, this article highlights
      key gaps in the understanding of the diverse relationships between bleeding
      phenotype and factors such as joint health, genetic susceptibility, laboratory
      parameters, quality of life and management of pain. Early prophylaxis is a
      potential 'gold standard' therapy and issues surrounding inhibitor development,
      variations in its clinical use and long-term outcomes are discussed.
      Comprehensive treatment should be individualized for all patients (including
      those with mild or moderate haemophilia and carriers). Wherever possible all
      patients should be given prophylaxis. However, adult patients with a milder
      haemophilia phenotype may be candidates for ceasing prophylaxis and switching to
      on-demand treatment. Regardless, all treatment (on-demand and prophylaxis) should
      be tailored towards both the patient's personal needs and their clinical profile.
      In addition, as the associations between risk factors (psychosocial, condition
      related and treatment-related) and clinical features are unique to each patient,
      an individualized approach is required to enable patients to alter their
      behaviour in response to them. The practical methodologies needed to reach this
      goal of individualized haemophilia care, and the health economic implications of
      this strategy, are ongoing topics for discussion. 

PMID- 25396765
TI  - Roles of the red cell distribution width and neutrophil/lymphocyte ratio in
      predicting thrombolysis failure in patients with an ST-segment elevation
      myocardial infarction.
AB  - Red cell distribution width (RDW) and the neutrophil/lymphocyte ratio (NLR) are
      predictors of cardiovascular risk that have been shown to correlate with impaired
      reperfusion and increased morbidity and mortality in patients with an ST-segment
      elevation myocardial infarction (STEMI). We hypothesized that RDW and the NLR
      would be associated with failed thrombolysis. One hundred and two STEMI patients
      were included in the study; 32 had failed thrombolysis while the other 70
      fulfilled the criteria for successful thrombolysis. Thrombolysis failure was
      defined as a need for rescue percutaneous coronary intervention (PCI), in
      hospital mortality, unplanned PCI during hospitalization or complete occlusion of
      the culprit coronary artery on follow-up angiography. RDWs were compared between
      patients with failed or successful thrombolysis. There were no significant
      differences in the demographic or clinical baseline characteristics of the two
      groups. The mean RDW was significantly higher in the failed thrombolysis group
      than in the successful thrombolysis group (P = 0.028). The cutoff RDW value for
      failed thrombolysis was more than 14.3 fl with a sensitivity of 90.6% and a
      specificity of 61.4% (area under the curve, 0.774; 95% confidence interval, 0.680
      0.851; P < 0.001) on receiver operating characteristics curve analysis. In
      addition, the prevalence of failed thrombolysis was significantly higher in
      patients with an RDW more than 14.3 fl than in those with an RDW of 14.3 fl or
      less (51.8 and 6.5%, respectively, P < 0.001 by multivariate analysis). The NLR
      was significantly higher in patients with an RDW more than 14.3 fl than in those
      with an RDW 14.3 fl or less (4 +/- 2.5 and 2.8 +/- 1.5, respectively, P = 0.007).
      RDW and the NLR may be used as adjunctive readily available factors for
      assessment of thrombolysis outcome upon admission.

PMID- 25396766
TI  - TENI: A comprehensive battery for cognitive assessment based on games and
      technology.
AB  - TENI (Test de Evaluacion Neuropsicologica Infantil) is an instrument developed to
      assess cognitive abilities in children between 3 and 9 years of age. It is based
      on a model that incorporates games and technology as tools to improve the
      assessment of children's capacities. The test was standardized with two Chilean
      samples of 524 and 82 children living in urban zones. Evidence of reliability and
      validity based on current standards is presented. Data show good levels of
      reliability for all subtests. Some evidence of validity in terms of content, test
      structure, and association with other variables is presented. This instrument
      represents a novel approach and a new frontier in cognitive assessment. Further
      studies with clinical, rural, and cross-cultural populations are required.

PMID- 25396768
TI  - Mosquito surveillance for prevention and control of emerging mosquito-borne
      diseases in Portugal - 2008-2014.
AB  - Mosquito surveillance in Europe is essential for early detection of invasive
      species with public health importance and prevention and control of emerging
      pathogens. In Portugal, a vector surveillance national program-REVIVE (REde de
      VIgilancia de VEctores)-has been operating since 2008 under the custody of
      Portuguese Ministry of Health. The REVIVE is responsible for the nationwide
      surveillance of hematophagous arthropods. Surveillance for West Nile virus (WNV)
      and other flaviviruses in adult mosquitoes is continuously performed. Adult
      mosquitoes-collected mainly with Centre for Disease Control light traps baited
      with CO2-and larvae were systematically collected from a wide range of habitats
      in 20 subregions (NUTS III). Around 500,000 mosquitoes were trapped in more than
      3,000 trap nights and 3,500 positive larvae surveys, in which 24 species were
      recorded. The viral activity detected in mosquito populations in these years has
      been limited to insect specific flaviviruses (ISFs) non-pathogenic to humans.
      Rather than emergency response, REVIVE allows timely detection of changes in
      abundance and species diversity providing valuable knowledge to health
      authorities, which may take control measures of vector populations reducing its
      impact on public health. This work aims to present the REVIVE operation and to
      expose data regarding mosquito species composition and detected ISFs.

PMID- 25396767
TI  - Mobile phone-based mHealth approaches for public health surveillance in sub
      Saharan Africa: a systematic review.
AB  - Whereas mobile phone-based surveillance has the potential to provide real-time
      validated data for disease clustering and prompt respond and investigation,
      little evidence is available on current practice in sub-Sahara Africa. The
      objective of this review was to examine mobile phone-based mHealth interventions
      for Public Health surveillance in the region. We conducted electronic search in
      MEDLINE, EMBASE, IEE Xplore, African Index Medicus (AIM), BioMed Central, PubMed
      Central (PMC), the Public Library of Science (PLoS) and IRIS for publications
      used in the review. In all, a total of nine studies were included which focused
      on infectious disease surveillance of malaria (n = 3), tuberculosis (n = 1) and
      influenza-like illnesses (n = 1) as well as on non-infectious disease
      surveillance of child malnutrition (n = 2), maternal health (n = 1) and routine
      surveillance of various diseases and symptoms (n = 1). Our review revealed that
      mobile phone-based surveillance projects in the sub-Saharan African countries are
      on small scale, fragmented and not well documented. We conclude by advocating for
      a strong drive for more research in the applied field as well as a better
      reporting of lessons learned in order to create an epistemic community to help
      build a more evidence-based field of practice in mHealth surveillance in the
      region.

PMID- 25396769
TI  - A novel socioeconomic measure using individual housing data in cardiovascular
      outcome research.
AB  - BACKGROUND: To assess whether the individual housing-based socioeconomic status
      (SES) measure termed HOUSES was associated with post-myocardial infarction (MI)
      mortality. METHODS: The study was designed as a population-based cohort study,
      which compared post-MI mortality among Olmsted County, Minnesota, USA, residents
      with different SES as measured by HOUSES using Cox proportional hazards models.
      Subjects' addresses at index date of MI were geocoded to real property data to
      formulate HOUSES (a z-score for housing value, square footage, and numbers of
      bedrooms and bathrooms). Educational levels were used as a comparison for the
      HOUSES index. RESULTS: 637 of the 696 eligible patients with MI (92%) were
      successfully geocoded to real property data. Post-MI survival rates were 60% (50
      72), 78% (71-85), 72% (60-87), and 87% (81-93) at 2 years for patients in the
      first (the lowest SES), second, third, and fourth quartiles of HOUSES,
      respectively (p < 0.001). HOUSES was associated with post-MI all-cause mortality,
      controlling for all variables except age and comorbidity (p = 0.036) but was not
      significant after adjusting for age and comorbidity (p = 0.24). CONCLUSIONS:
      Although HOUSES is associated with post-MI mortality, the differential mortality
      rates by HOUSES were primarily accounted for by age and comorbid conditions.
      HOUSES may be useful for health disparities research concerning cardiovascular
      outcomes, especially in overcoming the paucity of conventional SES measures in
      commonly used datasets.

PMID- 25396770
TI  - Influence of daily individual meteorological parameters on the incidence of acute
      coronary syndrome.
AB  - BACKGROUND: A nationwide study was conducted to explore the short term
      association between daily individual meteorological parameters and the incidence
      of acute coronary syndrome (ACS) treated with coronary emergency catheter
      interventions in the Republic of Slovenia, a south-central European country.
      METHOD: We linked meteorological data with daily ACS incidence for the entire
      population of Slovenia, for the population over 65 years of age and for the
      population under 65 years of age. Data were collected daily for a period of 4
      years from 1 January 2008 to 31 December 2011. In line with existing studies, we
      used a main effect generalized linear model with a log-link-function and a
      Poisson distribution of ACS. RESULTS AND CONCLUSIONS: Three of the studied
      meteorological factors (daily average temperature, atmospheric pressure and
      relative humidity) all have relevant and significant influences on ACS incidences
      for the entire population. However, the ACS incidence for the population over 65
      is only affected by daily average temperature, while the ACS incidence for the
      population under 65 is affected by daily average pressure and humidity. In terms
      of ambient temperature, the overall findings of our study are in line with the
      findings of the majority of contemporary European studies, which also note a
      negative correlation. The results regarding atmospheric pressure and humidity are
      less in line, due to considerable variations in results. Additionally, the number
      of available European studies on atmospheric pressure and humidity is relatively
      low. The fourth studied variable-season-does not influence ACS incidence in a
      statistically significant way.

PMID- 25396771
TI  - Shifting sands: adapting the multidisciplinary team model to technological and
      organizational innovations in cancer care.

PMID- 25396772
TI  - Cancer care in the UK: we need to be more ambitious.

PMID- 25396773
TI  - Making an IMPAQTT on the quality of life of cancer patients.

PMID- 25396774
TI  - Fosbretabulin for the treatment of anaplastic thyroid cancer.
AB  - Fosbretabulin tromethamine is a vascular disrupting agent, which is a type of
      drug that is designed to damage the vasculature (blood vessels) of cancer tumors,
      causing central necrosis. This drug showed activity against anaplastic thyroid
      cancer that was demonstrated in orthotopic xenograft models as well as in Phase
      I/II trials with or without carboplatin and paclitaxel combination therapy. In
      all of these studies, fosbretabulin was well tolerated.

PMID- 25396776
TI  - Treatments for gastrointestinal stromal tumors that are resistant to standard
      therapies.
AB  - The advent of the tyrosine kinase inhibitors imatinib and sunitinib dramatically
      revolutionized the therapeutic approach to gastrointestinal stromal tumor (GIST)
      and improved the outcomes of patients who were affected by this rare tumor,
      becoming the standard first- and second-line systemic therapies for
      advanced/metastatic GIST. Most patients obtain good, durable responses to
      treatment; nevertheless, almost all patients develop acquired resistance, which
      is commonly related to secondary mutations in receptors. Resistance represents an
      important clinical problem in oncology, underlining the need to identify novel
      agents in order to overcome it. In this article, we focus on the most recent
      developments in the therapy of advanced GIST that is resistant to standard
      therapies, including both new single drugs or drug-drug combinations, and the
      integration of systemic and locoregional treatment.

PMID- 25396775
TI  - Cancer stem cells: are they responsible for treatment failure?
AB  - Overcoming resistance to standard anticancer treatments represents a significant
      challenge. The interest regarding cancer stem cells, a cellular population that
      has the ability to self-renew and to propagate the tumor, was prompted by
      experimental evidence delineating the molecular mechanisms that are selectively
      activated in this cellular subset in order to survive chemotherapy. This has also
      stimulated combination strategies aimed at rendering cancer stem cells vulnerable
      to anticancer agents. Moreover, cancer stem cells offer a unique opportunity for
      modeling human cancers in mice, thus emerging as a powerful tool for testing
      novel drugs and combinations in a simulation of human disease. These novel animal
      models may lay the foundation for a new generation of clinical trials aimed at
      anticipating the benefit to patients of anticancer therapies.

PMID- 25396777
TI  - Nuclear medicine in urological cancers: what is new?
AB  - The diffusion of PET/computed tomography has opened up a new role for nuclear
      imaging in urological oncology. Prostate cancer is evaluated with choline ((11)C
      or (18)F) PET due to a lack of sensitivity of (18)F-fluorodeoxyglucose (FDG).
      However, many new tracers, such as (18)F-fluorocyclobutane-1-carboxylic acid and
      (68)Ga-prostate-specific membrane antigen, are under investigation, offering
      promising results in the particular setting of radically treated patients with
      biochemical relapse. The performance of (18)F-FDG depends on the histological
      type; indeed, renal cell cancer may present variable metabolic uptake. In this
      field, mainly antibodies labeled with positron emitters are under clinical
      evaluation. Finally, (18)F-FDG PET/computed tomography has been proven to show
      good accuracy in detecting metastatic testicular and bladder cancers, despite not
      having valid results in detecting local disease. The urological cancer diagnostic
      process is currently under continuous development.

PMID- 25396778
TI  - Assessment of radiologic response to targeted therapies in patients with
      hepatocellular carcinoma.
AB  - The development of new treatment options for hepatocellular carcinoma has changed
      not only the way in which cancer is treated, but also how it is diagnosed,
      especially the assessment of tumor response. The traditional radiologic methods,
      which are mainly based on the evaluation of changes in tumor size, are considered
      to be insufficiently sensitive and unreliable for determining tumor progression
      when targeted therapies such as sorafenib are involved. Several lines of research
      are currently focusing on the development of new assessment tools that try to
      combine morphological and vascular functional data in order to obtain an accurate
      measurement of tumor characteristics, such as volume, density or vascularization.
      This article presents some of the new instruments that have reported positive
      results.

PMID- 25396779
TI  - Third- and further-line therapy in advanced non-small-cell lung cancer patients:
      an overview.
AB  - Non-small-cell lung cancer (NSCLC) treatment has led to improved efficacy and
      compliance due to individual tailoring of the therapeutic options and the use of
      strategies based on both clinical characteristics and histological and biological
      features of the disease. In nonsquamous NSCLC, novel agents, such as pemetrexed
      and bevacizumab, have improved survival in the first-line setting. Maintenance
      therapy with pemetrexed and erlotinib resulted in improved progression-free
      survival compared with second-line therapy at disease progression. In the second
      line setting, pemetrexed improves survival in nonsquamous NSCLC compared with
      docetaxel, and erlotinib has shown a survival benefit compared with best
      supportive care in patients who did not previously receive an EGF receptor
      inhibitor. Although the benefit of first- and second-line treatment over best
      supportive care alone has been firmly established, the role of further-line
      treatment remains controversial. This article summarizes the state-of-the-art
      treatments in this setting.

PMID- 25396781
TI  - Understanding Condom Use Decision Making Among Homeless Youth Using Event-Level
      Data.
AB  - This is one of the first qualitative event-based studies to understand the
      various mechanisms through which multiple factors influence condom use decision
      making among homeless youth. Event-level interviews that explore characteristics
      of the environment surrounding sexual events were conducted with 29 youth who
      were asked to describe two recent sexual encounters. In thematic analyses of data
      across events, reasons that youth gave for engaging in unprotected sex included
      the expectation of having sex and use of alternative methods of protection
      against pregnancy. Other nonevent factors that influenced condom use decision
      making were related to attributes of the partnership (e.g., testing, trust and
      love, and assessments of risk) and attributes of the youth (e.g., perceptions of
      diseases, concerns over pregnancy, and discomfort using condoms). Additional
      event analyses conducted within the same individuals found that decision making
      was influenced by multiple interacting factors, with different pathways operating
      for event and nonevent factors. Future interventions should consider taking a
      multilevel and individualized approach that focuses on event-based determinants
      of risky sex in this population. 

PMID- 25397324
TI  - Self-referenced luminescence thermometry with Sm(3+) doped TiO2 nanoparticles.
AB  - The performance of Sm(3+) doped TiO2 nanoparticles for luminescence temperature
      sensing was tested over a temperature range from room to 110  degrees C. The
      Sm(3+) ions were incorporated into TiO2 nanocrystals using hydrolytic sol-gel
      route. Microstructural characterization of the obtained material was performed
      using transmission electron microscopy and x-ray diffraction measurements.
      Luminescence emission spectra of Sm(3+) doped TiO2 nanoparticles consists of two
      distinct spectral regions: the high energy region associated with the trap
      emission of the TiO2 host, and the low energy region with well-resolved emission
      peaks of the Sm(3+) ions. The ratio between Sm(3+) emission and TiO2 trap
      emission shows strong temperature dependence, and is tested for temperature
      sensing. The relative sensor sensitivity was found to be higher than 1%  degrees
      C(-1) over given temperature range with the maximum value of 10.54%  degrees C(
      1) at 57.5  degrees C. Lifetime data derived from the Sm(3+) emission decay
      revealed that time-resolved measurements provide comparable quality of
      temperature sensing as corresponding ratiometric measurements, with a maximum
      relative sensitivity of 10.14%  degrees C(-1) at 66.5  degrees C. 

PMID- 25397325
TI  - Generation of insulin-producing cells from the mouse liver using beta cell
      related gene transfer including Mafa and Mafb.
AB  - Recent studies on the large Maf transcription factors have shown that Mafb and
      Mafa have respective and distinctive roles in beta-cell development and
      maturation. However, whether this difference in roles is due to the timing of the
      gene expression (roughly, expression of Mafb before birth and of Mafa after
      birth) or to the specific function of each gene is unclear. Our aim was to
      examine the functional differences between these genes that are closely related
      to beta cells by using an in vivo model of beta-like cell generation. We
      monitored insulin gene transcription by measuring bioluminescence emitted from
      the liver of insulin promoter-luciferase transgenic (MIP-Luc-VU) mice. Adenoviral
      gene transfers of Pdx1/Neurod/Mafa (PDA) and Pdx1/Neurod/Mafb (PDB) combinations
      generated intense luminescence from the liver that lasted for more than 1 week
      and peaked at 3 days after transduction. The peak signal intensities of PDA and
      PDB were comparable. However, PDA but not PDB transfer resulted in significant
      bioluminescence on day 10, suggesting that Mafa has a more sustainable role in
      insulin gene activation than does Mafb. Both PDA and PDB transfers ameliorated
      the glucose levels in a streptozotocin (STZ)-induced diabetic model for up to 21
      days and 7 days, respectively. Furthermore, PDA transfer induced several gene
      expressions necessary for glucose sensing and insulin secretion in the liver on
      day 9. However, a glucose tolerance test and liver perfusion experiment did not
      show glucose-stimulated insulin secretion from intrahepatic beta-like cells.
      These results demonstrate that bioluminescence imaging in MIP-Luc-VU mice
      provides a noninvasive means of detecting beta-like cells in the liver. They also
      show that Mafa has a markedly intense and sustained role in beta-like cell
      production in comparison with Mafb. 

PMID- 25397327
TI  - Short-term visual deprivation, tactile acuity, and haptic solid shape
      discrimination.
AB  - Previous psychophysical studies have reported conflicting results concerning the
      effects of short-term visual deprivation upon tactile acuity. Some studies have
      found that 45 to 90 minutes of total light deprivation produce significant
      improvements in participants' tactile acuity as measured with a grating
      orientation discrimination task. In contrast, a single 2011 study found no such
      improvement while attempting to replicate these earlier findings. A primary goal
      of the current experiment was to resolve this discrepancy in the literature by
      evaluating the effects of a 90-minute period of total light deprivation upon
      tactile grating orientation discrimination. We also evaluated the potential
      effect of short-term deprivation upon haptic 3-D shape discrimination using a set
      of naturally-shaped solid objects. According to previous research, short-term
      deprivation enhances performance in a tactile 2-D shape discrimination task -
      perhaps a similar improvement also occurs for haptic 3-D shape discrimination.
      The results of the current investigation demonstrate that not only does short
      term visual deprivation not enhance tactile acuity, it additionally has no effect
      upon haptic 3-D shape discrimination. While visual deprivation had no effect in
      our study, there was a significant effect of experience and learning for the
      grating orientation task - the participants' tactile acuity improved over time,
      independent of whether they had, or had not, experienced visual deprivation. 

PMID- 25397328
TI  - Trauma advanced practice nursing: the centrifugal force of a trauma service.

PMID- 25397329
TI  - Advanced Practice Nursing in Trauma: It's a good thing.

PMID- 25397330
TI  - STN News and Notes.

PMID- 25397331
TI  - Acute care nurse practitioners in trauma care: results of a role survey and
      implications for the future of health care delivery.
AB  - The role of acute care nurse practitioners (ACNPs) in trauma care has evolved
      over time. A survey was performed with the aim of describing the role across the
      United States. There were 68 respondents who depicted the typical trauma ACNP as
      being a 42-year-old woman who works full-time at a level I American College of
      Surgeons verified trauma center. Trauma ACNPs typically practice with 80% of
      their time for clinical care and are based on a trauma and acute care surgery
      service. They are acute care certified and hold several advanced certifications
      to supplement their nursing license.

PMID- 25397332
TI  - Detection of missed injuries in a pediatric trauma center with the addition of
      acute care pediatric nurse practitioners.
AB  - Missed injuries contribute to increased morbidity in trauma patients. A
      retrospective chart review was conducted of pediatric trauma patients from 2010
      to 2013 with a documented missed injury. A significant percentage of missed
      injuries were identified (3.01% during July 2012 to December 2013 vs 0.39% during
      January 2010 to July 2012) with the addition of acute care trained pediatric
      nurse practitioners to the trauma service at a pediatric trauma center. The
      increase is thought to be due to improvement in charting, consistent personnel
      performing tertiary examinations, and improved radiology reads of outside films.

PMID- 25397334
TI  - Evaluation of a virtual geriatric trauma institute.
AB  - Geriatric trauma patients require specialized care. Objective of this study was
      to compare outcomes for geriatric trauma patients before and after the
      implementation of a virtual geriatric trauma institute. This is a retrospective
      chart review of 583 trauma patients older than 65 years admitted to a rural level
      1 trauma center before and after the implementation of a geriatric trauma
      institute. Length of stay was decreased from 4.99 to 3.9 days (P = .0014).
      Emergency department length of stay was decreased by approximately 10 minutes (P
      = .059), and time from the emergency department to the operating room was
      decreased by 470 minutes (P = .262). 

PMID- 25397335
TI  - Blunt chest trauma.
AB  - Blunt chest trauma is associated with a wide range of injuries, many of which are
      life threatening. This article is a case study demonstrating a variety of
      traumatic chest injuries, including pathophysiology, diagnosis, and treatment.
      Literature on the diagnosis and treatment was reviewed, including both
      theoretical and research literature, from a variety of disciplines. The role of
      the advance practice nurse in trauma is also discussed as it relates to
      assessment, diagnosis, and treatment of patients with traumatic chest injuries. 

PMID- 25397337
TI  - Trauma registry reengineered.
AB  - A successful trauma registry balances accuracy of abstraction and timeliness of
      case submissions to achieve quality performance. Staffing to achieve quality
      performance is a challenge at times based on competitive institutional need. The
      aim of this performance improvement timing study was to identify trauma registry
      job responsibilities and redesign the responsibilities to create increased
      abstraction time and maintain accuracy of data abstraction. The outcome is
      measured by case submission rates with existing staffing and interrater
      reliability outcomes. 

PMID- 25397338
TI  - Advanced practice nursing, health care teams, and perceptions of team
      effectiveness.
AB  - This article summarizes the results of an extensive review of the organizational
      and health care literature of advanced practice nursing (APN) roles, health care
      teams, and perceptions of team effectiveness. Teams have a long history in health
      care. Managers play an important role in mobilizing resources, guiding
      expectations of APN roles in teams and within organizations, and facilitating
      team process. Researchers have identified a number of advantages to the addition
      of APN roles in health care teams. The process within health care teams are
      dynamic and responsive to their surrounding environment. It appears that teams
      and perceptions of team effectiveness need to be understood in the broader
      context in which the teams are situated. Key team process are identified for team
      members to perceive their team as effective. The concepts of teamwork,
      perceptions of team effectiveness, and the introduction of APN roles in teams
      have been studied disparately. An exploration of the links between these concepts
      may further our understanding the health care team's perceptions of team
      effectiveness when APN roles are introduced. Such knowledge could contribute to
      the effective deployment of APN roles in health care teams and improve the
      delivery of health care services to patients and families. 

PMID- 25397339
TI  - Violence-related mild traumatic brain injury in women: identifying a triad of
      postinjury disorders.
AB  - Violence against women whether from domestic partner abuse, sex trafficking
      injuries, or sexual assault is a pervasive health problem without racial or
      social boundaries. Regardless of cause, violence results in a complex triad of
      physical, emotional, and psychological injuries. There is clear evidence that
      female victims of violence or "battered women" experience brain injury. What is
      less certain is whether the constellations of events surrounding brain injury
      including postconcussion syndrome, depression, and posttraumatic stress disorder
      are acute symptoms after the brain injury, premorbid as a result of persistent
      abuse, or a synergistic triad of combined disorders as a result of the injuries.
      The purpose of this article is to examine the relationship between physical
      violence-associated mild traumatic brain injury (MTBI) and postinjury cognitive,
      emotional, and psychological disorders. The review of the literature addresses
      epidemiological factors associated with domestic partners and sexual violence,
      abuse and health outcomes in women, physical injury, and its consequences. Along
      with MTBI, a triad of disorders is hypothesized that includes postconcussion
      syndrome, depression, and posttraumatic stress disorder. Screening for MTBI and
      the triad of disorders is advocated, and assessment methods are offered. 

PMID- 25397340
TI  - Creating a comprehensive bicycle safety program.
AB  - Trauma centers must play a role in injury prevention. Pediatric trauma centers
      have the ability to create injury prevention programs targeting all children.
      After analyzing our trauma registry data, we determined that bicycle injuries are
      a significant mechanism of injury in children and developed strategies aimed at
      preventing such injuries. Along with support from Kohl's Cares, we are able to
      achieve our mission of keeping children in our community healthy and safe. Our
      comprehensive bicycle safety program is targeted to various ages and learning
      styles and aims to increase bicycle safety and helmet use among children in our
      region. 

PMID- 25397341
TI  - Against medical advice.
AB  - Patients who leave the hospital against medical advice (AMA) present a challenge
      and concern to health care providers. Patients may leave AMA for a variety of
      reasons. Nurses play a vital role in patients considering an AMA discharge. Most
      of all, nurses can help by not perpetuating the concepts that AMA means you leave
      with nothing. Nurses must ensure that patients leave with information about their
      injuries, possible issues of concern after discharge, medications or
      prescriptions for medications, and follow-up information, and always stress to
      patients that at any time they may return to the hospital for additional care.

PMID- 25397342
TI  - The effect of secular trends in the classroom furniture mismatch: support for
      continuous update of school furniture standards.
AB  - In order to create safer schools, the Chilean authorities published a Standard
      regarding school furniture dimensions. The aims of this study are twofold: to
      verify the existence of positive secular trend within the Chilean student
      population and to evaluate the potential mismatch between the anthropometric
      characteristics and the school furniture dimensions defined by the mentioned
      standard. The sample consists of 3078 subjects. Eight anthropometric measures
      were gathered, together with six furniture dimensions from the mentioned
      standard. There is an average increase for some dimensions within the Chilean
      student population over the past two decades. Accordingly, almost 18% of the
      students will find the seat height to be too high. Seat depth will be considered
      as being too shallow for 42.8% of the students. It can be concluded that the
      Chilean student population has increased in stature, which supports the need to
      revise and update the data from the mentioned Standard. PRACTITIONER SUMMARY:
      Positive secular trend resulted in high levels of mismatch if furniture is
      selected according to the current Chilean Standard which uses data collected more
      than 20 years ago. This study shows that school furniture standards need to be
      updated over time.

PMID- 25397345
TI  - Decision limits and the reporting of cardiac troponin: Meeting the needs of both
      the cardiologist and the ED physician.
AB  - Cardiac troponin is the preferred biomarker for defining the acute coronary
      syndrome and acute myocardial infarction. Currently, the only decision limit
      formally endorsed with regard to the cardiac troponins is the 99th percentile.
      This is a "rule-in" criterion, intended to ensure that only persons with the
      acute coronary syndrome are reviewed. The 99th percentile is an arbitrary cut
      point and there are many problems associated with its application, including
      defining a truly healthy population, the difficulty of standardisation of cardiac
      troponin assays, especially but not only cardiac troponin I, and the effects of
      age and sex on this parameter. The Emergency Department (ED) screens many more
      persons for possible acute coronary syndromes than actually have the condition
      and their needs are best met by a "rule-out" test that enables them to clear
      their busy departments of the many persons who do not actually have the
      condition. The needs of the ED are not optimally met using the 99th percentile.
      The index of individuality for the cardiac troponins is small and significant
      changes consistent with an acute coronary syndrome can occur without the 99th
      percentile being exceeded. It appears that the ED may be better served by use of
      delta troponin changes rather than the 99th percentile, but there are problems
      with this approach, particularly in persons who present late when troponin
      release has plateaued. In addition, there are many non-acute coronary syndrome
      causes for cardiac troponin release. The needs of the cardiologist and the ED
      physician are so different that it may be inappropriate for both groups to use
      the same diagnostic criteria for cardiac troponin, and it is of great importance
      that cardiac troponin measurement be used as only one part of the assessment of
      the person presenting with possible acute coronary syndrome.

PMID- 25397346
TI  - Engaging social work practitioners in research: challenges and opportunities.
AB  - Contemporary emphasis on measuring and evaluating observable, behavioral outcomes
      reflects a major change in the profession toward greater empirical basis for
      social work practice. This intellectual and methodological shift has created a
      gap between practitioners and researchers. While social work practitioners
      definitely should be more knowledgeable and receptive to interventions that have
      proven to be effective in helping people, social work academics must pay more
      attention to the realities of social work practitioners who struggle daily with
      expanding caseloads, ever-increasing time pressures to help clients whose lives
      are embedded in poverty, unemployment, oppression, racism, homelessness, and
      violence. 

PMID- 25397347
TI  - The impact of poverty, chronic illnesses, and health insurance status on out-of
      pocket health care expenditures in later life.
AB  - This study aims to examine poverty, chronic illnesses, health insurance, and
      health care expenditures, within the context of a political economy of aging
      perspective. Subsamples of 1,773 older adults from the Medical Expenditure Panel
      Survey were selected for analyses. The results showed that chronic illnesses
      influenced out-of-pocket health care costs. Older persons with more than one
      health insurance spent less on out-of-pocket health care costs. The results have
      implications for health care social workers concerned with the growing costs of
      chronic illnesses, implementing integrated care, and advocating for extending
      public health insurance coverage especially for our most impoverished older
      adults. 

PMID- 25397348
TI  - Ethical dilemmas faced by hospice social workers.
AB  - Ethical decision making is critically important in hospice social work. Through
      in-depth interviews, researchers explored ethical dilemmas faced by 14 hospice
      social workers and the processes they used to move toward resolution. The
      dilemmas were integrated into a framework focused on the sources of ethical
      conflict: the client system, the agency, and the profession. Processes involved
      in resolving ethical dilemmas included consulting with other professionals,
      weighing the pros and cons of options, and bringing about desired outcomes.
      Findings suggest that hospice teams should be provided with opportunities to
      meaningfully discuss ethical decision making. Further, the involvement of social
      workers in administrative leadership is recommended to increase the likelihood
      that discipline-specific perspectives are incorporated into formal policies and
      procedures that shape practice in ethically complex situations. 

PMID- 25397350
TI  - Implications of smart wear technology for family caregiving relationships: focus
      group perceptions.
AB  - Technological advances in monitoring vulnerable care-recipients are on the rise.
      Recent and future development of Smart Wear technology (devices integrated into
      clothing that monitor care-recipients) might assist family caregivers with tasks
      related to caring for young children, relatives with disabilities, and frail
      spouses or parents. However, the development and use of this technology in family
      caregiving contexts is in its infancy. Focus group interviews of family
      caregivers were conducted to explore perspectives regarding the potential
      integration of Smart Wear technology into their family caregiving. Responses were
      analyzed qualitatively for themes related to perceptions of how Smart Wear could
      impact relationships between caregivers and care-recipients. Three major themes
      emerged: quality and quantity of interaction, boundary issues, and implications
      for anxiety. Implications and recommendations are discussed regarding maximizing
      the potential benefits of Smart Wear technology in ways that promote and protect
      healthy relationships among caregivers and care-recipients. 

PMID- 25397349
TI  - Early life circumstances as contributors to HIV infection.
AB  - Adolescents may come from family settings that heighten their vulnerability to
      early sexual initiation, promiscuity and sexual exploitation. Using qualitative
      data, we illustrated how early life and family circumstances including neglectful
      or dysfunctional parenting, sexual abuse, and unstable housing placed young women
      on a risk trajectory for HIV infection. Five representative cases from a sample
      of 26 adolescent and young adult HIV-infected females (ages 16-24) who
      participated in a study about the disease-related adaptive challenges they faced
      are discussed. Study participants were recruited from five New York City
      adolescent HIV clinics that provided comprehensive specialty medical and
      ancillary social services to adolescents and young adults with the disease. The
      findings revealed that these young women's unmet need for love, protection, and
      feeling valued left them vulnerable to exploitive relationships with men who were
      often significantly older and resulted in their HIV infection. 

PMID- 25397352
TI  - Augmenting performance feedback does not affect 4 km cycling time-trials in the
      heat.
AB  - We compared the effects of (1) accurate and (2) surreptitiously augmented
      performance feedback on power output and physiological responses to a 4000 m time
      trial in the heat. Nine cyclists completed a baseline (BaseL) 4000 m time-trial
      in ambient temperatures of 30 degrees C, followed by two further 4000 m time
      trials at the same temperature, randomly assigning the participants to an
      accurate (ACC; accurate feedback of baseline) or deceived (DEC; 2% increase above
      baseline) feedback group. The total power output (PO) and aerobic (Paer) and
      anaerobic (Pan) contributions were determined at 0.4 km stages during the time
      trials, alongside measurements of rectal (Trec) and skin (Tskin) temperatures.
      There were no differences (P > 0.05) in any of the variables between BaseL, ACC
      and DEC, despite increases (P < 0.05) in Trec and Tskin. Typical pacing profiles
      were demonstrated; however, there was no interaction (P > 0.05) between feedback
      condition and time-trial stage. Providing surreptitiously augmented performance
      feedback to well-trained cyclists did not alter their performance or
      physiological responses to a 4000 m time-trial in a hot environment. The assumed
      influence of augmented performance feedback was nullified in the heat, perhaps
      reflecting a central down-regulation of exercise intensity in response to an
      increased body temperature.

PMID- 25397353
TI  - Noah syndrome: a variant of Diogenes syndrome accompanied by animal hoarding
      practices.
AB  - Noah syndrome is a variant of Diogenes syndrome that presents as hoarding a large
      number of animals. Predisposing factors for developing this disorder are
      situations of psychosocial stress and loneliness. However, the medical conditions
      of the sufferer, which can represent the organic substrate for the development of
      this psychopathology, should be considered. 

PMID- 25397354
TI  - Exploring the views of nurses on the cardiometabolic health nurse in mental
      health services in australia.
AB  - People with serious mental illness experience premature death due to higher rates
      of cardiometabolic conditions (e.g. cardiovascular disease, diabetes) than the
      general population. Mental health services often do not provide sufficient
      cardiometabolic clinical care to address these risks. The cardiometabolic health
      nurse (CHN) role has been suggested as a strategy for ensuring integrated care is
      provided and sustained. The views of nurses in mental health would be essential
      in informing the viability and development for this initiative. This paper
      presents the findings of open-ended comments from a cross-sectional online survey
      of nurses working in mental health in Australia (n  =  643) eliciting views about
      the possible introduction of the cardiometabolic nurse. Thematic analysis was
      undertaken, of 133 open comments on this topic. The findings suggest that nurses
      see the specialist role as suitable and valuable for mental health services. Some
      nurses voiced concern about specialisation leading to fragmentation (e.g. in
      responsibilities for physical health, division of mental and physical health
      care, and less emphasis on equipping all nurses with comprehensive care skills),
      especially for settings where generalist nursing was seen as already available.
      The findings suggest this role is viewed favourably by nurses, provided that it
      is consistent with holistic and comprehensive care. Empirical research is needed
      to see whether this role increases holism (as valued by consumers and nurses) and
      cardiometabolic outcomes. 

PMID- 25397355
TI  - Travel bans will increase the damage wrought by ebola.

PMID- 25397356
TI  - Immunosuppressive treatment combined with nucleoside analog is superior to
      nucleoside analog only in the treatment of severe thrombocytopenia in patients
      with cirrhosis associated with hepatitis B in China: A multicenter, observational
      study.
AB  - No effective treatment has been identified for patients of liver cirrhosis (LC)
      associated with hepatitis B virus (HBV) and severe thrombocytopenia. We aimed to
      explore the effectiveness and safety of low-dose prednisone or cyclosporine A
      (CsA) combined with nucleoside analog (NA) in patients with severe
      thrombocytopenia associated with HBV-related LC. We included 145 consecutive
      compensated HBV-associated LC patients with severe thrombocytopenia between 1
      January 2006 and 31 December 2013. We divided the patients into three groups by
      treatment strategy, including NA only (n = 57), NA plus prednisone (n = 46), and
      NA plus CsA (n = 42). We analyzed the platelet counts, bleeding events, liver
      function, replication of HBV, and outcomes in each group. At all time points
      during this observation, the platelet counts in prednisone or CsA group were
      higher than those in the NA only group. There are significant differences in the
      cumulative rates of bleeding events among the three groups. The platelet counts
      and treatment were factors associated with bleeding events in multivariate
      analysis. The differences in HBV-DNA negative rates, HBV-DNA elevated rates,
      normal serum alanine transaminase rates, serum alanine transaminase elevated more
      than two times the baseline rates, and HBeAg seropositive conversion ratio among
      the groups did not reach statistical significance. The adverse events in our
      study were, in general, mild and balanced among the three treatment groups.
      Treatment with low-dose prednisone or CsA plus NA could elevate the platelet
      counts and reduce the risk of bleeding events in HBV LC with severe
      thrombocytopenia.

PMID- 25397357
TI  - Sociodemographic characteristics and drug abuse patterns of adolescents admitted
      for substance use disorder treatment in Istanbul.
AB  - BACKGROUND: Adolescent substance use is an increasing major health problem in
      developing countries. OBJECTIVES: To evaluate the sociodemographic
      characteristics and drug abuse patterns of children and youth seeking treatment
      in Turkey. METHODS: This retrospective study reviewed the demographic and
      clinical data of substance users who visited the substance addiction treatment
      clinic for children and youth in Bakirkoy Research and Training Hospital for
      Psychiatry, Neurology and Neurosurgery in Istanbul, between January 2011 and
      December 2012. RESULTS: The sample comprised of 1969 children and youth aged
      between 11 and 20 (346 female and 1623 male). Cannabis (60.1%), followed by
      solvents/inhalants (38.3%) and ecstasy (33.4%), were the most prevalent
      substances used. The use of solvents/inhalants was more common among males,
      whereas ecstasy and cocaine use were more common among females. The mean age for
      the onset of substance use was 13 years. The proportion of polysubstance use was
      60.2%. There was a mean duration of 2.28 +/- 1.91 years between the first
      substance use and seeking treatment. The risk factors for most of the drug usage
      were onset of substance use at a young age, gender, treatment admission at older
      ages, higher parental criminal history, and having substance using parents or
      relatives. CONCLUSION: Findings of the very early onset of substance and
      polysubstance use indicated easy accessibility of legal and illicit substances by
      children and youth in Istanbul. These findings on Turkish children and youth who
      seek substance use treatment can be useful in developing preventive early
      interventions and treatment facilities.

PMID- 25397358
TI  - Examining the role of serostatus disclosure on unprotected sex among people
      living with HIV.
AB  - Given the increasing prevalence of HIV, it is important to identify factors
      associated with safer sex behaviors between people living with HIV and their
      partners. Utilizing a diverse sample of 242 HIV-infected adults [n=69 men who
      have sex with men (MSM); n=68 men who have sex with women (MSW); n=105 women who
      have sex with men (WSM)], we examined the association between serostatus
      disclosure and unprotected anal or vaginal intercourse (UAVI) and the moderating
      effect of sexual behavior group on this association. Overall, 88.7% disclosed to
      their current partner. Approximately 18.8% of MSM, 17.7% of MSW, and 29.5% of WSM
      reported UAVI. Controlling for age, time since diagnosis, and partner serostatus,
      we found main effects on UAVI for disclosure and sexual behavior group;
      specifically, disclosure was inversely related to unprotected sex [AOR=0.09, 95%
      CI (0.02, 0.43), p<0.001], and MSM were less likely to engage in UAVI relative to
      WSM [AOR=0.11, 95% CI (0.17, 0.82), p<0.05]. However, the relationship between
      disclosure and UAVI was not moderated by sexual behavior group. Future strategies
      that aim to increase disclosure to partners may consider focusing on its value as
      a means by which to reduce sexual risk behavior.

PMID- 25397359
TI  - Exploring the association between dispositional cancer worry, perceived risk, and
      physical activity among college women.
AB  - OBJECTIVE: In this study, the authors explored the association between
      dispositional cancer worry (DCW), risk perceptions (RP), and physical activity
      (PA) among college females. PARTICIPANTS: Four hundred fifty-one females from a
      midwestern university completed an online survey in September/October 2012.
      METHODS: DCW severity, DCW frequency, RP, and PA were measured along with
      qualitative data about PA as cancer prevention. RESULTS: Sixty-nine percent of
      participants did not meet PA recommendations. DCW severity was a significant
      predictor of meeting PA recommendations (odds ratio = 1.2, 95% confidence
      interval [1.00, 1.38]; p = .05). Qualitative data revealed a lack of knowledge
      about breast cancer risk and PA as cancer prevention. CONCLUSIONS: College women
      do not engage in enough PA nor feel at risk for developing breast cancer. A lack
      of knowledge exists about the cancer prevention benefit of PA. Results indicate a
      need for PA interventions that both educate breast cancer risk and motivate
      health protective behaviors.

PMID- 25397360
TI  - Reanalysis and semantic persistence in native and non-native garden-path
      recovery.
AB  - We report the results from an eye-movement monitoring study investigating how
      native and non-native speakers of English process temporarily ambiguous sentences
      such as While the gentleman was eating the burgers were still being reheated in
      the microwave, in which an initially plausible direct-object analysis is first
      ruled out by a syntactic disambiguation (were) and also later on by semantic
      information (being reheated). Both participant groups showed garden-path effects
      at the syntactic disambiguation, with native speakers showing significantly
      stronger effects of ambiguity than non-native speakers in later eye-movement
      measures but equally strong effects in first-pass reading times. Ambiguity
      effects at the semantic disambiguation and in participants' end-of-trial
      responses revealed that for both participant groups, the incorrect direct-object
      analysis was frequently maintained beyond the syntactic disambiguation. The non
      native group showed weaker reanalysis effects at the syntactic disambiguation and
      was more likely to misinterpret the experimental sentences than the native group.
      Our results suggest that native language (L1) and non-native language (L2)
      parsing are similar with regard to sensitivity to syntactic and semantic error
      signals, but different with regard to processes of reanalysis. 

PMID- 25397361
TI  - Allogeneic versus autologous derived cell sources for use in engineered bone
      ligament-bone grafts in sheep anterior cruciate ligament repair.
AB  - The use of autografts versus allografts for anterior cruciate ligament (ACL)
      reconstruction is controversial. The current popular options for ACL
      reconstruction are patellar tendon or hamstring autografts, yet advances in
      allograft technologies have made allogeneic grafts a favorable option for repair
      tissue. Despite this, the mismatched biomechanical properties and risk of
      osteoarthritis resulting from the current graft technologies have prompted the
      investigation of new tissue sources for ACL reconstruction. Previous work by our
      lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs
      generated from an allogeneic cell source develop structural and functional
      properties similar to those of native ACL and vascular and neural structures that
      exceed those of autologous patellar tendon grafts. In this study, we investigated
      the effectiveness of our tissue-engineered ligament constructs fabricated from
      autologous versus allogeneic cell sources. Our preliminary results demonstrate
      that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB
      grafts show similar histological and mechanical outcomes indicating that the
      autologous grafts are a viable option for ACL reconstruction. These data indicate
      that our tissue-engineered autologous ligament graft could be used in clinical
      situations where immune rejection and disease transmission may preclude allograft
      use. 

PMID- 25397362
TI  - Non-toxic plant metabolites regulate Staphylococcus viability and biofilm
      formation: a natural therapeutic strategy useful in the treatment and prevention
      of skin infections.
AB  - In the present study, the efficacy of generally recognised as safe (GRAS)
      antimicrobial plant metabolites in regulating the growth of Staphylococcus aureus
      and S. epidermidis was investigated. Thymol, carvacrol and eugenol showed the
      strongest antibacterial action against these microorganisms, at a subinhibitory
      concentration (SIC) of <= 50 MUg ml(-1). Genistein, hydroquinone and resveratrol
      showed antimicrobial effects but with a wide concentration range (SIC = 50-1,000
      MUg ml(-1)), while catechin, gallic acid, protocatechuic acid, p-hydroxybenzoic
      acid and cranberry extract were the most biologically compatible molecules (SIC
      >= 1000 MUg ml(-1)). Genistein, protocatechuic acid, cranberry extract, p
      hydroxybenzoic acid and resveratrol also showed anti-biofilm activity against S.
      aureus, but not against S. epidermidis in which, surprisingly, these metabolites
      stimulated biofilm formation (between 35% and 1,200%). Binary combinations of
      cranberry extract and resveratrol with genistein, protocatechuic or p
      hydroxibenzoic acid enhanced the stimulatory effect on S. epidermidis biofilm
      formation and maintained or even increased S. aureus anti-biofilm activity. 

PMID- 25397363
TI  - Magnetic three-dimensional graphene solid-phase extraction of chlorophenols from
      honey samples.
AB  - A novel magnetic three-dimensional graphene nano-composite (3D-G@Fe3O4) with a
      high surface area was synthesised by a vacuum freeze-dried method. Due to its
      high surface area, specific 3D nanoporous structure and excellent magnetic
      properties, it can be used as a magnetic solid-phase extraction adsorbent. Some
      chlorophenols in a honey samples were enriched by this nanocomposite prior to
      their determination by HPLC with ultraviolet detection. Factors that affect the
      extraction efficiency, such as the amount of 3D-G@Fe3O4, extraction time, sample
      pH, ionic strength and desorption conditions, were investigated and optimised.
      Under the optimum conditions, good linearity existed in the range of 10.0-1000.0
      ng g(-1). The enrichment factors of the method for the analytes were in the range
      from 101 to 248. The limits of detection of the method (S/N = 3) were 1.0-1.5 ng
      g(-1). The recoveries of the method for the analytes at spiking levels of 100.0
      and 400.0 ng g(-1) were in the range of 93.2-98.9%. The results showed that the
      proposed method is simple, reliable and sensitive. It will be a useful tool for
      the routine monitoring of chlorophenols in honey products. 

PMID- 25397364
TI  - Health problems, complex life, and consanguinity among ethnic minority Muslim
      women in Nepal.
AB  - BACKGROUND: Marriage between blood relatives is common among Muslim ethnic
      minority population in Nepal. Albeit, the adverse effects of such a
      consanguineous marriage on health are controversial. OBJECTIVE: To determine the
      prevalence, characteristics and health outcomes related to consanguineous
      marriage. DESIGN: A cross-sectional survey was carried out using a cluster
      sampling technique to select the respondents. A total of 400 women aged 15-49
      years were interviewed from September 2011 to February 2012. A structured
      questionnaire was administered through face-to-face meetings. Adjusted odds
      ratios (AOR) were estimated by a stepwise likelihood ratio method with binary
      logistic regression. RESULTS: The overall prevalence of consanguinity was 36.7%.
      The median age at marriage and age at first childbirth was 15 and 18 years,
      respectively. The association of being in a consanguineous marriage among women
      whose husband's education level were secondary or higher was 3.35 (95% CI 1.56,
      7.12) times greater than among those whose husbands were unable to read and
      write. Woman who have consanguineous marriage were less likely to have (AOR 0.46,
      95% CI 0.26, 0.82) used contraceptive than those who have non-consanguineous
      marriage. Women who have consanguineous marriage were more (AOR 1.80; 95% CI
      0.90, 3.61) likely to have birth defect in their children than those who have non
      consanguineous marriage. The association of having a history of death after live
      birth among women who experienced emotional violence was 2.60 (95% CI 1.36, 5.00)
      and physical violence 2.15 (95% CI 1.16, 3.93) times greater than among those who
      did not experience violence. CONCLUSIONS: Several factors like husband's
      education and dowry practices are associated with consanguineous marriage.
      Further, these factors including consanguineous marriage and marital violence are
      also accountable for negative health consequences. Thus, multicomponent
      interventions are needed in order to improve the health condition of Nepalese
      Muslim community in rural area.

PMID- 25397365
TI  - Convection-enhanced delivery to the central nervous system.
AB  - Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties
      permit direct, homogeneous, targeted perfusion of CNS regions with putative
      therapeutics while bypassing the blood-brain barrier. Development of surrogate
      imaging tracers that are co-infused during drug delivery now permit accurate,
      noninvasive real-time tracking of convective infusate flow in nervous system
      tissues. The potential advantages of CED in the CNS over other currently
      available drug delivery techniques, including systemic delivery, intrathecal
      and/or intraventricular distribution, and polymer implantation, have led to its
      application in research studies and clinical trials. The authors review the
      biophysical principles of convective flow and the technology, properties, and
      clinical applications of convective delivery in the CNS. 

PMID- 25397366
TI  - Surgery for primary supratentorial brain tumors in the United States, 2000-2009:
      effect of provider and hospital caseload on complication rates.
AB  - OBJECT: The object of this study was to examine how procedural volume and patient
      demographics impact complication rates and value of care in those who underwent
      biopsy or craniotomy for supratentorial primary brain tumors. METHODS: The
      authors conducted a retrospective cohort study using data from the Nationwide
      Inpatient Sample (NIS) on 62,514 admissions for biopsy or resection of
      supratentorial primary brain tumors for the period from 2000 to 2009. The main
      outcome measures were in-hospital mortality, routine discharge proportion, length
      of hospital stay, and perioperative complications. Associations between these
      outcomes and hospital or surgeon case volumes were examined in logistic
      regression models stratified across patient characteristics to control for
      presentation of disease and comorbid risk factors. The authors further computed
      value of care, defined as the ratio of functional outcome to hospital charges.
      RESULTS: High-case-volume surgeons and hospitals had superior outcomes. After
      adjusting for patient characteristics, high-volume surgeon correlated with
      reduced complication rates (OR 0.91, p=0.04) and lower in-hospital mortality (OR
      0.43, p<0.0001). High-volume hospitals were associated with reduced in-hospital
      mortality (OR 0.76, p=0.003), higher routine discharge proportion (OR 1.29,
      p<0.0001), and lower complication rates (OR 0.93, p=0.04). Patients treated by
      high-volume surgeons were less likely to experience postoperative hematoma,
      hydrocephalus, or wound complications. Patients treated at high-volume hospitals
      were less likely to experience mechanical ventilation, pulmonary complications,
      or infectious complications. Worse outcomes tended to occur in African American
      and Hispanic patients and in those without private insurance, and these
      demographic groups tended to underutilize high-volume providers. CONCLUSIONS: A
      high-volume status for hospitals and surgeons correlates with superior value of
      care, as well as reduced in-hospital mortality and complications. These findings
      suggest that regionalization of care may enhance patient outcomes and improve
      value of care for patients with primary supratentorial brain tumors.

PMID- 25397367
TI  - Vertebral artery transposition for revascularization of the posterior
      circulation: a critical assessment of temporary and permanent complications and
      outcomes.
AB  - OBJECT: Despite advances in medical management and endovascular therapies,
      including the introduction of statins, antiplatelet agents, and drug-eluting
      stents, some patients experience medically refractory vertebrobasilar
      insufficiency and may benefit from robust surgical revascularization. The aim of
      this study was to evaluate such patients after surgical revascularization,
      emphasizing long-term outcomes and rates of complications. METHODS: The authors
      retrospectively identified 22 patients (5 women and 17 men) whose mean age was
      69.1 years (range 48-81 years) who underwent revascularization of the posterior
      circulation via a proximal vertebral artery-carotid artery transposition between
      2005 and 2013. The patients' conditions before surgery were clinically
      summarized, and long-term outcomes and complication rates after surgery were
      evaluated. RESULTS: All the patients were symptomatic before surgery although
      they received the best medical therapy as defined by their primary care
      physician. Presenting symptoms consisted of stroke, transient ischemic attacks
      (TIAs), and/or findings attributable to posterior circulation hypoperfusion.
      There were no deaths associated with revascularization surgery. The postoperative
      complication rate was 45.5%, which included 3 cases of recurrent laryngeal nerve
      palsy, 1 case of thoracic duct injury, 2 cases of TIA, and 4 cases of Horner's
      syndrome. The thoracic duct injury was identified intraoperatively and ligated
      without sequelae, all the TIAs resolved within 24 hours of surgery, all 4
      sympathetic plexus injuries resolved, and all but 1 of the recurrent laryngeal
      nerve palsies resolved, resulting in a 4.5% complication rate in a mean follow-up
      period of 8.8 months. All the patients had resolution of their presenting
      symptoms, and a single patient had symptomatic restenosis that required stenting
      and angioplasty, resulting in a restenosis rate of 4.5%. CONCLUSIONS: Despite the
      optimization of medical therapies and lifestyle modifications, a select subset of
      patients with posterior vascular circulation insufficiency remains. In the
      authors' experience, vertebral artery-carotid artery transposition provides a
      surgical option with relatively low long-term complication and restenosis rates
      that are comparable or lower than those reported with endovascular treatment.

PMID- 25397368
TI  - Stem cell signature in glioblastoma: therapeutic development for a moving target.
AB  - Tumor heterogeneity of adult high-grade glioma (HGG) is recognized in 3 major
      subtypes based on core gene signatures. However, the molecular signatures and
      clinical implications of glioma stem cells (GSCs) in individual HGG subtypes
      remain poorly characterized. Recently genome-wide transcriptional analysis
      identified two mutually exclusive GSC subtypes with distinct dysregulated
      signaling and metabolic pathways. Analysis of genetic profiles and phenotypic
      assays distinguished proneural (PN) from mesenchymal (MES) GSCs and revealed a
      striking correlation with the corresponding PN or MES HGGs. Similar to HGGs with
      a MES signature, MES GSCs display more aggressive phenotypes both in vitro and in
      vivo. Furthermore, MES GSCs are markedly resistant to radiation as compared with
      PN GSCs, consistent with the relative radiation resistance of MES GBM compared
      with other subtypes. A systems biology approach has identified a set of
      transcription factors as the master regulators for the MES signature. Metabolic
      reprogramming in MES GSCs has also been noticed with the prominent activation of
      the glycolytic pathway, comprising aldehyde dehydrogenase (ALDH) family genes.
      This review summarizes recent progress in the characterization of the molecular
      signature in distinct HGG and GSC subtypes and plasticity between different GSC
      subtypes as well as between GSCs and non-GSCs in HGG tumors. Clinical
      implications of the translational GSC research are also discussed. 

PMID- 25397370
TI  - Society for Pediatric Research 2014 Presidential Address: The test of our
      progress.

PMID- 25397371
TI  - Can we be as good as our mentors?

PMID- 25397372
TI  - Basal cell carcinoma of the external auditory canal.
AB  - Basal cell carcinomas of the EAC are known to be locally aggressive, although
      they are not associated with regional lymph node metastasis.

PMID- 25397373
TI  - Endoscopic view of an ostium in a concha bullosa of the superior turbinate.
AB  - A specific outflow tract or ostium of the superior turbinate, as was seen in this
      case, has been infrequently described or imaged.

PMID- 25397374
TI  - Fish bone impaction in the supraglottis.
AB  - The most common sites of fish bone impaction are the tonsils, tonsillar pillars,
      tongue base, valleculae, and piriform fossa. Impaction in the supraglottic area
      is extremely uncommon.

PMID- 25397375
TI  - Transoral approach to a deep-lobe parotid tumor.

PMID- 25397376
TI  - Giant-cell tumor of the tendon sheath in the external auditory canal.
AB  - Giant-cell tumor of the tendon sheath (GCTTS) and pigmented villonodular
      synovitis belong to the same type of benign proliferative lesions originating in
      the synovia that usually affect the joints, bursae, and tendon sheaths. They
      frequently involve the hands, knees, ankles, and feet. We report a case of GCTTS
      in the external auditory canal in a 53-year-old woman who presented with hearing
      loss, fullness, and a sessile lesion protruding from the anterior wall of her
      external ear canal. The 1.5-cm diameter mass was spherical, well encapsulated,
      firm, and covered with normal skin. The lesion was completely excised, and the
      patient's symptoms resolved. No recurrence was detected at 2 years of follow-up. 

PMID- 25397377
TI  - Salivary gland choristoma of the middle ear.
AB  - Choristoma of the middle ear is a rare condition characterized by the presence of
      normal salivary gland tissue in the middle ear space. Salivary gland choristomas
      are benign lesions that are frequently associated with ossicular chain and facial
      nerve anomalies. Total surgical excision is indicated when there is no risk of
      damaging the facial nerve. We describe a new case of salivary gland choristoma of
      the middle ear, and we discuss the etiology, histologic features, and management
      of such lesions. Our patient was a 22-year-old woman in whom we surgically
      removed a whitish retrotympanic mass. Intraoperatively, we also detected an
      ossicular chain malformation. Histologic examination of the choristoma revealed
      the presence of salivary gland tissue. Furthermore, the lesion contained an
      extensive and previously undescribed component: a well-defined pseudostratified
      respiratory-type epithelium, similar to that of a normal eustachian tube. Ten
      months after removal of the choristoma, we surgically repaired the ossicular
      chain anomalies. No recurrence was noted on follow-up. 

PMID- 25397378
TI  - Complete second branchial cleft anomaly presenting as a fistula and a tonsillar
      cyst: an interesting congenital anomaly.
AB  - Branchial cleft anomalies make up 30% of all pediatric neck masses, but complete
      second branchial cleft anomalies are extremely rare. We report an unusual case of
      a complete second branchial cleft anomaly that presented as a draining neck
      fistula and a tonsillar cyst in an otherwise healthy 3-month-old girl. At the age
      of 7 months, the patient had been experiencing feeding difficulties, and there
      was increasing concern about the risk of persistent infections. At that point,
      the anomaly was excised in its entirety. Our suspicion that the patient had a
      complete second branchial cleft anomaly was confirmed by imaging, surgical
      excision, and histopathologic analysis. 

PMID- 25397379
TI  - Submental nodular fasciitis: report of an unusual case.
AB  - A 30-year-old woman presented for evaluation of a hard, enlarging, submental mass
      that was fixed to the underlying mandible. Fine-needle aspiration cytology
      initially led to a diagnosis of pleomorphic adenoma, which was unusual given the
      superficial location of the lesion on computed tomography. The lesion was a well
      defined rim-enhancing mass, and it had displaced adjacent structures medially.
      Intraoperatively, the mass was found to abut against and erode the mandibular
      cortex. A diagnosis of nodular fasciitis was established by histologic analysis.
      Such a location for this tumor is unusual. The prognosis for patients with this
      benign condition is excellent following complete surgical excision. We discuss
      the clinical presentation and the cytologic, histologic, and radiologic features
      of this uncommon entity. 

PMID- 25397380
TI  - Management of soft palate agenesis in Nager syndrome with an elongated,
      superiorly based pharyngeal flap.
AB  - Nager syndrome, or preaxial acrofacial dysostosis, is associated with aberrant
      development of the first and second branchial arch structures, as well as
      abnormal development of the limb buds. It is a rare disorder, and its clinical
      manifestations have not been completely defined. Absence of the soft palate has
      been reported in patients with Nager syndrome. In this report we describe the use
      of an elongated, superiorly based pharyngeal flap for the treatment of severe
      velopharyngeal insufficiency in a patient with Nager syndrome and absence of the
      soft palate. We also describe the dysmorphisms associated with Nager syndrome and
      present a differential diagnosis for the condition. 

PMID- 25397381
TI  - Primary malignant melanoma of the external auditory canal extending into the
      preauricular area and scalp.
AB  - Malignant melanomas in the head and neck region are uncommon. When they do occur,
      they usually represent a metastasis. To the best of our knowledge, only 11 cases
      of primary malignant melanoma of the external auditory canal have been previously
      reported in the English-language literature since 1954. We describe a new case,
      which occurred in a 72-year-old woman who presented with a large, lobulated,
      pigmented mass with ulcerated bleeding on its surface. The patient was scheduled
      for surgery, but during preoperative preparations she developed signs of rapid
      dissemination and metastases to the liver and lungs, and she died of multiple
      organ failure within 3 weeks of presentation. Apart from the rarity of malignant
      melanoma of the external auditory canal, this case included other extraordinary
      features that make it noteworthy. Our experience with this case underscores the
      importance of early diagnosis and prompt initiation of treatment for patients
      with this potentially fatal malignancy. 

PMID- 25397382
TI  - Primary laryngeal tuberculosis: An unusual cause of hoarseness.
AB  - Tuberculosis (TB) of the larynx is usually associated with concomitant pulmonary
      TB, but approximately 20% of cases represent primary disease. We report the case
      of an 85-year-old woman with asthma who presented with a 6-month history of
      persistent hoarseness. Bronchoscopy confirmed the presence of a lesion in the
      hemilarynx, and histology identified tuberculoid granulomas that were suggestive
      of TB. Treatment with a combination of isoniazid, rifampicin, pyrazinamide, and
      ethambutol led to a complete resolution of symptoms. A high index of suspicion
      for laryngeal TB is required in patients who present with hoarseness. 

PMID- 25397383
TI  - Mucormycosis (Mucor fungus ball) of the maxillary sinus.
AB  - A fungus ball is an extramucosal fungal proliferation that completely fills one
      or more paranasal sinuses and usually occurs as a unilateral infection. It is
      mainly caused by Aspergillus spp in an immunocompetent host, but some cases of
      paranasal fungal balls reportedly have been caused by Mucor spp. A Mucor fungus
      ball is usually found in the maxillary sinus and/or the sphenoid sinus and may be
      black in color. Patients with mucormycosis, or a Mucor fungal ball infection,
      usually present with facial pain or headache. On computed tomography, there are
      no pathognomonic findings that are conclusive for a diagnosis of mucormycosis. In
      this article we report a case of mucormycosis in a 56-year-old woman and provide
      a comprehensive review of the literature on the "Mucor fungus ball." To the best
      of our knowledge, 5 case reports (8 patients) have been published in which the
      fungus ball was thought to be caused by Mucor spp. 

PMID- 25397384
TI  - Castleman disease of the parotid gland in a pediatric patient: a case report.
AB  - Castleman disease, also called angiofollicular lymph node hyperplasia, is a rare
      lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes.
      Affected patients usually present with mediastinal lymphadenopathy; sometimes
      other groups of lymph nodes are involved, with or without associated systemic
      manifestations. We report a case of Castleman disease involving the intraparotid
      lymph node in a 15-year-old boy who presented with a 3-month history of a
      painless swelling of the right parotid gland. Fine-needle aspiration cytology of
      the mass revealed only reactive hyperplasia. The diagnosis of Castleman disease
      was established on histopathologic examination of the resected mass. We discuss
      the clinical course, histopathologic features, radiologic characteristics, and
      management of Castleman disease of the parotid gland in a pediatric patient. 

PMID- 25397385
TI  - Hypopharyngeal hemangioma in an adult: a case report.
AB  - Hemangiomas of the postcricoid region have been reported almost exclusively in
      infants and young children. Our adult patient with symptoms of dysphagia and
      weight loss underwent transoral CO2 laser microsurgery of a postcricoid mass, and
      final pathologic examination confirmed the presence of a hemangioma. She is doing
      well after surgery, with an excellent voice, resolution of dysphagia, and no
      evidence of recurrence. There have been few cases of hypopharyngeal hemangioma in
      the adult population; to our knowledge, there have been no reports in the English
      language literature of adult patients diagnosed specifically with a postcricoid
      hemangioma. Otolaryngologists should be familiar with the presentation and
      treatment of this unusual entity. 

PMID- 25397386
TI  - A transoral surgical approach to a parapharyngeal-space pleomorphic adenoma.
AB  - It is relatively difficult to gain surgical access to pleomorphic adenomas of the
      parapharyngeal space. Since the lateral border is the mandible, gaining access to
      them can put several important neurovascular structures at risk. A number of
      surgical approaches have been developed to overcome this difficulty, and each has
      its advantages and disadvantages. We report the case of a 59-year-old woman with
      a parapharyngeal-space pleomorphic adenoma that was accessed via a transoral
      approach. Transoral approaches are controversial and rarely used. However, we
      feel that for a selected group of tumors, this approach provides clear benefits
      by decreasing cosmetic and functional disability while providing good surgical
      access to the tumor. 

PMID- 25397387
TI  - Synchronous double cancers of the hypopharynx: malignant fibrous histiocytoma and
      squamous cell carcinoma.
AB  - We report a unique case of synchronous double hypopharyngeal tumors in a 39-year
      old man. The patient presented with a 1-year history of a muffled voice and mild
      odynophagia. Laryngoscopy detected two grossly different tumors in the
      hypopharynx: a malignant fibrous histiocytoma (MFH) in the postcricoid area and a
      squamous cell carcinoma (SCC) in the posterior pharyngeal wall. Chemoradiotherapy
      was administered, and the patient was free of disease at 23 months of follow-up.
      Synchronous double cancers of the hypopharynx that feature different oncotypes
      are very rare, especially those that include an MFH. In fact, to the best of our
      knowledge, no case of synchronous MFH and SCC of the hypopharynx has been
      previously reported in the literature. Because the number of reported cases of
      MFH in the hypopharynx is so small, no consensus exists with respect to the
      preferred option among the various treatment choices. 

PMID- 25397388
TI  - An unusual case of acute periorbital swelling.
AB  - Periorbital swelling is frequently encountered in ear, nose, and throat practices
      and, as it may be secondary to acute sinusitis, delayed diagnosis may lead to
      significant morbidity. We describe the case of a 24-year-old man with acute
      ethmoid-maxillary sinusitis and ipsilateral facial swelling particularly
      involving the periorbital area. We also discuss the workup that led to the
      formulation of an unusual diagnosis. 

PMID- 25397389
TI  - Medullary thyroid carcinoma presenting as a supraglottic mass.
AB  - We report a rare case of medullary thyroid carcinoma that presented as a
      metastasis to the supraglottic larynx. A 92-year-old man with a 3-month history
      of voice change and airway obstruction was diagnosed with medullary thyroid
      carcinoma metastatic to the supraglottis. Excision of the mass, total
      thyroidectomy, and elective neck dissection were recommended, but the patient
      declined because of his advanced age. Medullary carcinoma of the thyroid gland is
      a rare neuroendocrine tumor with a poor prognosis when associated with a distant
      metastasis. To the best of our knowledge, this is the first case of a medullary
      carcinoma of the thyroid presenting as a supraglottic mass. Total thyroidectomy,
      neck dissection, and surgical excision of the entire tumor comprise the treatment
      of choice. 

PMID- 25397390
TI  - Osteoma of the middle ear.
AB  - Management of middle ear osteoma can be complicated when the round window is
      obliterated. Therefore, the patient should be informed about what to expect prior
      to surgery.

PMID- 25397391
TI  - Rapid growth of a laryngeal oncocytic cyst after surgical irritation.

PMID- 25397392
TI  - Distal nasolacrimal duct showing the valve of Hasner.
AB  - Recognition of the location of the nasolacrimal duct opening is important to
      prevent its damage while performing an intranasal inferior meatal antrostomy or
      creating a window transantrally in the inferior meatal wall during a Caldwell-Luc
      procedure.

PMID- 25397393
TI  - A rare occurrence of a fungus ball in the sphenoethmoid recess.
AB  - A fungus ball usually appears as a calcification within the sinus, suggesting the
      presence of a foreign body.

PMID- 25397394
TI  - Sinonasal tract mucosal melanoma.

PMID- 25397395
TI  - Congenital airway anomaly of double aortic arch in a 2-day-old infant.
AB  - Double aortic vascular ring is a complete vascular ring that is formed when the
      distal portion of the right dorsal aorta fails to regress and the ascending aorta
      bifurcates to surround and compress both trachea and esophagus and rejoins to
      form the descending aorta.

PMID- 25397396
TI  - Black thyroid.

PMID- 25397397
TI  - A persistent left superior vena cava, with the accessory nerve passing through a
      duplicate segment of the left internal jugular vein: a unique presentation.
AB  - The internal jugular vein and the spinal accessory nerve are important landmarks
      during neck dissection; unexpected variations in their positions can result in
      inadvertent iatrogenic damage to adjacent structures. We report the case of a 79
      year-old man who was found during neck dissection to have a duplicate segment of
      his left internal jugular vein (IJV), a persistent left superior vena cava, and
      an absent right superior vena cava. The spinal accessory nerve passed through the
      duplicate section of the IJV. A MEDLINE search found no previously reported case
      of these anomalies occurring together. We also review 10 previously reported
      cases of IJV duplication. Finally, we discuss the embryologic and anatomic
      background of these malformations so that otolaryngologists may be aware that
      identification of such anomalies may help to prevent postoperative morbidity. 

PMID- 25397398
TI  - Lingual hamartoma associated with a cleft palate in a newborn.
AB  - A hamartoma is a benign malformation of native tissue that may occur in any area
      of the body. Hamartoma of the tongue is a rare developmental lesion. We describe
      the case of a pendulant lingual hamartoma in a 2-day-old girl that had not been
      identified on prenatal ultrasonography. We also review the utility of prenatal
      imaging options, the role of preoperative imaging, the mechanical relationship
      between lingual hamartoma and cleft palate, the histopathology of this tumor,
      surgical treatment, and emergency airway management. 

PMID- 25397400
TI  - beta-NaMnO2: a high-performance cathode for sodium-ion batteries.
AB  - There is much interest in Na-ion batteries for grid storage because of the lower
      projected cost compared with Li-ion. Identifying Earth-abundant, low-cost, and
      safe materials that can function as intercalation cathodes in Na-ion batteries is
      an important challenge facing the field. Here we investigate such a material,
      beta-NaMnO2, with a different structure from that of NaMnO2 polymorphs and other
      compounds studied extensively in the past. It exhibits a high capacity (of ca.
      190 mA h g(-1) at a rate of C/20), along with a good rate capability (142 mA h g(
      1) at a rate of 2C) and a good capacity retention (100 mA h g(-1)after 100 Na
      extraction/insertion cycles at a rate of 2C). Powder XRD, HRTEM, and (23)Na NMR
      studies revealed that this compound exhibits a complex structure consisting of
      intergrown regions of alpha-NaMnO2 and beta-NaMnO2 domains. The collapse of the
      long-range structure at low Na content is expected to compromise the
      reversibility of the Na extraction and insertion processes occurring upon charge
      and discharge of the cathode material, respectively. Yet stable, reproducible,
      and reversible Na intercalation is observed. 

PMID- 25397401
TI  - Evaluation of soil contamination indices in a mining area of Jiangxi, China.
AB  - There is currently a wide variety of methods used to evaluate soil contamination.
      We present a discussion of the advantages and limitations of different soil
      contamination assessment methods. In this study, we analyzed seven trace elements
      (As, Cd, Cr, Cu, Hg, Pb, and Zn) that are indicators of soil contamination in
      Dexing, a city in China that is famous for its vast nonferrous mineral resources
      in China, using enrichment factor (EF), geoaccumulation index (Igeo), pollution
      index (PI), and principal component analysis (PCA). The three contamination
      indices and PCA were then mapped to understand the status and trends of soil
      contamination in this region. The entire study area is strongly enriched in Cd,
      Cu, Pb, and Zn, especially in areas near mine sites. As and Hg were also present
      in high concentrations in urban areas. Results indicated that Cr in this area
      originated from both anthropogenic and natural sources. PCA combined with
      Geographic Information System (GIS) was successfully used to discriminate between
      natural and anthropogenic trace metals. 

PMID- 25397402
TI  - Residual antibiotics in decontaminated human cardiovascular tissues intended for
      transplantation and risk of falsely negative microbiological analyses.
AB  - We investigated the presence of antibiotics in cryopreserved cardiovascular
      tissues and cryopreservation media, after tissue decontamination with antibiotic
      cocktails, and the impact of antibiotic residues on standard tissue bank
      microbiological analyses. Sixteen cardiovascular tissues were decontaminated with
      bank-prepared cocktails and cryopreserved by two different tissue banks according
      to their standard operating procedures. Before and after decontamination, samples
      underwent microbiological analysis by standard tissue bank methods. Cryopreserved
      samples were tested again with and without the removal of antibiotic residues
      using a RESEP tube, after thawing. Presence of antibiotics in tissue homogenates
      and processing liquids was determined by a modified agar diffusion test. All
      cryopreserved tissue homogenates and cryopreservation media induced important
      inhibition zones on both Staphylococcus aureus- and Pseudomonas aeruginosa-seeded
      plates, immediately after thawing and at the end of the sterility test. The RESEP
      tube treatment markedly reduced or totally eliminated the antimicrobial activity
      of tested tissues and media. Based on standard tissue bank analysis, 50% of
      tissues were found positive for bacteria and/or fungi, before decontamination and
      2 out of 16 tested samples (13%) still contained microorganisms after
      decontamination. After thawing, none of the 16 cryopreserved samples resulted
      positive with direct inoculum method. When the same samples were tested after
      removal of antibiotic residues, 8 out of 16 (50%) were contaminated. Antibiotic
      residues present in tissue allografts and processing liquids after
      decontamination may mask microbial contamination during microbiological analysis
      performed with standard tissue bank methods, thus resulting in false negatives. 

PMID- 25397403
TI  - Notch2 controls prolactin and insulin-like growth factor binding protein-1
      expression in decidualizing human stromal cells of early pregnancy.
AB  - Decidualization, the transformation of the human uterine mucosa into the
      endometrium of pregnancy, is critical for successful implantation and embryonic
      development. However, key regulatory factors controlling differentiation of
      uterine stromal cells into hormone-secreting decidual cells have not been fully
      elucidated. Hence, we herein investigated the role of the Notch signaling pathway
      in human decidual stromal cells (HDSC) isolated from early pregnancy samples.
      Immunofluorescence of first trimester decidual tissues revealed expression of
      Notch2 receptor and its putative, membrane-anchored interaction partners Jagged1,
      Delta-like (DLL) 1 and DLL4 in stromal cells whereas other Notch receptors and
      ligands were absent from these cells. During in vitro differentiation with
      estrogen/progesterone (E2P4) and/or cyclic adenosine monophosphate (cAMP) HDSC
      constitutively expressed Notch2 and weakly downregulated Jagged1 mRNA and
      protein, measured by quantitative PCR (qPCR) and Western blotting, respectively.
      However, increased levels of DLL1 and DLL4 were observed in the decidualizing
      cultures. Transfection of a Notch luciferase reporter and qPCR of the Notch
      target gene hairy and enhancer of split 1 (HES1) revealed an induction of
      canonical Notch activity during in vitro differentiation. In contrast, treatment
      of HDSC with a chemical Notch/gamma-secretase inhibitor decreased cAMP/E2P4
      stimulated Notch luciferase activity, HES1 transcript levels and mRNA expression
      of the decidual marker genes prolactin (PRL) and insulin-like growth factor
      binding protein 1 (IGFBP1). Similarly, siRNA-mediated gene silencing or antibody
      mediated blocking of Notch2 diminished HES1, PRL and IGFBP1 mRNA levels as well
      as secreted PRL protein. In summary, the data suggest that canonical, Notch2
      dependent signaling plays a role in human decidualization. 

PMID- 25397404
TI  - A determination and comparison of urease activity in feces and fresh manure from
      pig and cattle in relation to ammonia production and pH changes.
AB  - Ammonia emission from animal production is a major environmental problem and has
      impacts on the animal health and working environment inside production houses.
      Ammonia is formed in manure by the enzymatic degradation of urinary urea and
      catalyzed by urease that is present in feces. We have determined and compared the
      urease activity in feces and manure (a urine and feces mixture) from pigs and
      cattle at 25 degrees C by using Michaelis-Menten kinetics. To obtain accurate
      estimates of kinetic parameters Vmax and K'm, we used a 5 min reaction time to
      determine the initial reaction velocities based on total ammoniacal nitrogen
      (TAN) concentrations. The resulting Vmax value (mmol urea hydrolyzed per kg wet
      feces per min) was 2.06+/-0.08 mmol urea/kg/min and 0.80+/-0.04 mmol urea/kg/min
      for pig feces and cattle feces, respectively. The K'm values were 32.59+/-5.65
      mmol urea/l and 15.43+/-2.94 mmol urea/l for pig feces and cattle feces,
      respectively. Thus, our results reveal that both the Vmax and K'm values of the
      urease activity for pig feces are more than 2-fold higher than those for cattle
      feces. The difference in urea hydrolysis rates between animal species is even
      more significant in fresh manure. The initial velocities of TAN formation are
      1.53 mM/min and 0.33 mM/min for pig and cattle manure, respectively. Furthermore,
      our investigation shows that the maximum urease activity for pig feces occurs at
      approximately pH 7, and in cattle feces it is closer to pH 8, indicating that the
      predominant fecal ureolytic bacteria species differ between animal species. We
      believe that our study contributes to a better understanding of the urea
      hydrolysis process in manure and provides a basis for more accurate and animal
      specific prediction models for urea hydrolysis rates and ammonia concentration in
      manures and thus can be used to predict ammonia volatilization rates from animal
      production. 

PMID- 25397406
TI  - Up-regulation of nerve growth factor in cholestatic livers and its
      hepatoprotective role against oxidative stress.
AB  - The role of nerve growth factor (NGF) in liver injury induced by bile duct
      ligation (BDL) remains elusive. This study aimed to investigate the relationship
      between inflammation and hepatic NGF expression, to explore the possible upstream
      molecules up-regulating NGF, and to determine whether NGF could protect
      hepatocytes from oxidative liver injury. Biochemical and molecular detection
      showed that NGF was up-regulated in cholestatic livers and plasma, and well
      correlated with systemic and hepatic inflammation. Conversely, systemic
      immunosuppression reduced serum NGF levels and resulted in higher mortality in
      BDL-treated mice. Immunohistochemistry showed that the up-regulated NGF was
      mainly localized in parenchymal hepatocytes. In vitro mechanistic study further
      demonstrated that TGF-beta1 up-regulated NGF expression in clone-9 and primary
      rat hepatocytes. Exogenous NGF supplementation and endogenous NGF overexpression
      effectively protected hepatocytes against TGF-beta1- and oxidative stress-induced
      cell death in vitro, along with reduced formation of oxidative adducted proteins
      modified by 4-HNE and 8-OHdG. TUNEL staining confirmed the involvement of anti
      apoptosis in the NGF-exhibited hepatoprotection. Moreover, NGF potently induced
      Akt phosphorylation and increased Bcl-2 to Bax ratios, whereas these molecular
      alterations by NGF were only seen in the H2O2-, but not TGF-beta1-treated
      hepatocytes. In conclusion, NGF exhibits anti-oxidative and hepatoprotective
      effects and is suggested to be therapeutically applicable in treating cholestatic
      liver diseases. 

PMID- 25397407
TI  - Quantitative evaluation of collagen crosslinks and corresponding tensile
      mechanical properties in mouse cervical tissue during normal pregnancy.
AB  - The changes in the mechanical integrity of the cervix during pregnancy have
      implications for a successful delivery. Cervical collagens are known to remodel
      extensively in mice with progressing gestation leading to a soft cervix at term.
      During this process, mature crosslinked collagens are hypothesized to be replaced
      with immature less crosslinked collagens to facilitate cervical softening and
      ripening. To determine the mechanical role of collagen crosslinks during normal
      mouse cervical remodeling, tensile load-to-break tests were conducted for the
      following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24
      hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and
      DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance
      liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI
      MS/MS). There were no significant changes in the total immature crosslink density
      (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31
      0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased
      significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15:
      0.026) and did not decrease with further gestation. The maturity ratio (total
      mature to total immature crosslinks) significantly decreased in early softening
      from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated
      significantly with a measure of tissue stiffness and strength, with the exception
      of the immature crosslink HLNL. This data provides quantitative evidence to
      support the hypothesis that as mature crosslinked collagens decline, they are
      replaced by immature collagens to facilitate increased tissue compliance in the
      early softening period from d6 to d15. 

PMID- 25397409
TI  - Antibody-free biomarker determination: exploring molecularly imprinted polymers
      for pro-gastrin releasing peptide.
AB  - Biomarker mass spectrometry assays are in high demand, and analysis of pro
      gastrin releasing peptide (ProGRP) as a small cell lung cancer marker has been
      recently investigated by mass spectrometry after immunoextraction. In this
      article, we introduce an assay based on molecularly imprinted polymers (MIPs)
      targeting the proteotypic peptide of ProGRP as a possible alternative to current
      immuno-based assay. The MIPs were prepared by surface-initiated reversible
      addition-fragmentation chain transfer polymerization and were introduced as
      sorbents for the cleanup and enrichment of a ProGRP signature peptide from
      tryptically treated serum samples. The use of an appropriate solid-phase
      extraction protocol allowed specific extraction of the target peptide while
      depleting other peptides that arose from the sample digestion, hence resulting in
      reduced background. The selective extraction of a ProGRP signature peptide, after
      digestion of serum samples, translates into a time- and cost-effective method
      suited for bottom-up analysis wherever targeted peptide extraction from complex
      matrices is required. 

PMID- 25397408
TI  - ZNF667/Mipu1 is a novel anti-apoptotic factor that directly regulates the
      expression of the rat Bax gene in H9c2 cells.
AB  - ZNF667/Mipu1, a C2H2-type zinc finger transcription factor, was suggested to play
      an important role in oxidative stress. However, none of the target genes or
      potential roles of ZNF667 in cardiomyocytes have been elucidated. Here, we
      investigated the functional role of ZNF667 in H9c2 cell lines focusing on its
      molecular mechanism by which it protects the cells from apoptosis. We found that
      ZNF667 inhibited the expression and the promoter activity of the rat proapoptotic
      gene Bax gene, and at the same time prevented apoptosis of H9c2 cells, induced by
      H2O2 and Dox. Western immunoblotting analysis revealed that ZNF667 also inhibited
      Bax protein expression, accompanied by attenuation of the mitochondrial
      translocation of Bax protein, induced by H2O2. EMSA and target detection assay
      showed that the purified ZNF667 fusion proteins could interact with the Bax
      promoter sequence in vitro, and this interaction was dependent upon the ZNF667
      DNA binding sequences or its core sequence in the promoter. Furthermore, ChIP
      assay demonstrated that a stimulus H2O2 could enhance the ability of ZNF667
      protein binding to the promoter. Finally, a reporter gene assay showed that
      ZNF667 could repress the activity of the Bax gene promoter, and the repression
      was dependent upon its binding to the specific DNA sequence in the promoter. Our
      work demonstrates that ZNF667 that confers cytoprotection is a novel regulator of
      the rat Bax gene, mediating the inhibition of the Bax mRNA and protein expression
      in H9c2 cardiomyocytes in response to H2O2 treatment. 

PMID- 25397411
TI  - Should screening for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-men
      who have sex with men be recommended?
AB  - INTRODUCTION: Sexually transmitted infections (STI) like Chlamydia trachomatis
      (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of
      HIV acquisition (1). It has been also described as a high prevalence of
      asymptomatic CT and NG infections in men who have sex with men (MSM) (2). The aim
      of this study was to know the prevalence of CT and/or NG infections in
      asymptomatic HIV-MSM and the related factors. MATERIALS AND METHODS: Prospective
      study of a cohort of asymptomatic HIV-MSM with follow-up in Malaga (southern
      Spain) during October 2012-May 2014. Patients with an opportunistic event or who
      received active antibiotic therapy for CT and/or NG in the previous month were
      excluded. All of them completed a questionnaire about sexual behaviour, barrier
      methods and recreational drugs use. Demographical, epidemiological, clinical,
      analytical and therapeutic data were also collected. Pharyngeal and rectal swabs,
      and urine samples were collected to be tested for CT and NG by nucleic acid
      amplification test (c4800 CT/NG. Roche Diagnostics, Mannheim, Germany) (3).
      STATISTICS ANALYSIS: SPSS 17.0. RESULTS: 255 patients were asked to participate
      and 248 of them accepted. Median age was 37.7 (30.6-46.3) years, median time
      since HIV diagnosis was 47.7 (10.5-104.1) months, and median CD4 cells count was
      607 (440-824) cell/uL. There were 195 (78.6%) patients on antiretroviral therapy;
      81.5% of them had undetectable viral load. 80.5% of the patients had a past
      history of STI. Infection by CT and/or NG was diagnosed in 24 (9.7%) patients.
      Overall four urine samples, two pharyngeal, and 15 rectal ones were positive for
      CT, and five pharyngeal and five rectal swabs were positive for NG. Two patients
      were co-infected by CT and NG: one with CT in urine and both in rectum, another
      with CT in urine and rectum and NG in pharynx. One patient presented CT in
      pharynx and rectum, and two patients NG in pharynx and rectum. Positive CT and/or
      NG tests were only related with detectable HIV viral load (OR 3.08, 95% CI 1.2
      7.4; p=0.01). It was not related with sexual behaviour, nor with alcohol or
      recreational drugs use. CONCLUSIONS: STI screening had a great acceptance in this
      population. There was a high prevalence of asymptomatic CT and/or NG infections.
      Rectum sample was the most effective one. Viral suppression could protect from
      these STI. Screening should be recommended in HIV-MSM.

PMID- 25397410
TI  - Effects of increased von Willebrand factor levels on primary hemostasis in
      thrombocytopenic patients with liver cirrhosis.
AB  - In patients with liver cirrhosis procoagulant and anticoagulant changes occur
      simultaneously. During primary hemostasis, platelets adhere to subendothelial
      structures, via von Willebrand factor (vWF). We aimed to investigate the
      influence of vWF on primary hemostasis in patients with liver cirrhosis.
      Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in
      cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure
      times with collagen and epinephrine (Col-Epi, upper limit of normal <= 165 s) or
      collagen and ADP (Col-ADP, upper limit of normal <= 118 s). If Col-Epi and Col
      ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF
      on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF
      levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72
      included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA
      100. They had mean closure times (+/- SD) of 180 +/- 62 s with Col-Epi and 160 +/
      70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027)
      and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100
      test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count >=
      150/nL and hematocrit >= 27.0%, pathological PFA-100 results were found. In
      thrombocytopenic (< 150/nL) patients with cirrhosis, normal PFA-100 results were
      associated with higher vWF-antigen levels (462.3 +/- 235.9% vs. 338.7 +/- 151.6%,
      P = 0.021). These results were confirmed by multivariate analysis in these
      patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody
      that significantly shortened or prolonged closure times, respectively. In
      conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of
      reduced platelet count in cirrhotic patients can at least be partly compensated
      by increased vWF levels. Recombinant vWF could be an alternative to platelet
      transfusions in the future.

PMID- 25397412
TI  - Prevalence of anal human papillomavirus infection and cytologic abnormalities
      among HIV-infected and HIV-uninfected men who have sex with men.
AB  - INTRODUCTION: Human papillomavirus (HPV) is responsible for 85% of anal cancers.
      Recently, anal cancer incidence has been increasing, particularly in men who have
      sex with men (MSM). Cytology may be a useful tool for the detection of anal
      precancerous lesions. We assessed the prevalence and determinants of anal HPV
      infection and cytologic abnormalities among HIV-infected and -uninfected MSM.
      MATERIALS AND METHODS: MSM >=18-year-old attending an STI clinic in Rome (Italy)
      were enrolled. Anal cytologic samples were collected in PreservCyt (Hologic)
      using a Dacron swab. The Linear Array HPV Genotyping Test (Roche Diagnostics) was
      used for the detection and genotyping of 37 mucosal HPV types. Liquid-based
      cytological slides were obtained using a ThinPrep2000 processor (Hologic). The
      morphology of the anal pap-test was classified following the Bethesda 2001
      guidelines. RESULTS: We enrolled 180 HIV-infected (median age 41 years, IQR 33
      47) and 438 HIV-uninfected MSM (median age 32 years, IQR: 27-39). Most of the
      individuals were Caucasian (92.2% and 97.0%, respectively). HPV prevalence, both
      overall (93.3% vs 72.4%, p<.001) and by high-risk (HR) HPV types (80.5% vs 56.0%,
      p<.001), was significantly higher among HIV-infected than HIV-uninfected
      individuals. HPV-multiple infections were evidenced in 48.2% of the HIV
      uninfected and 76.1% of the HIV-infected MSM (p<.001). HPV16 was the most
      prevalent genotype in both groups (23.3% in HIV-positive and 17.6% in HIV
      negative MSM). HPV6 and 84 were the most frequent low-risk types in both cohorts.
      Anal cytologic abnormalities were found in a significantly higher proportion of
      HIV-infected MSM (46.1% vs 27.9%, p<.001). H-SILs (high-grade squamous
      intraepithelial lesions) were exclusively observed among the HIV-infected
      individuals, although at a low prevalence (1.2%). CONCLUSIONS: A high prevalence
      of anal HPV infection and cytologic abnormalities was evidenced in both
      populations. Nonetheless, HIV-infected MSM showed a significantly higher rate of
      HPV infection and abnormal cytology, confirming that HIV-1 infection poses a
      significant risk for anal HPV infection as well as for anal cellular
      abnormalities. Screening for anal cancer, which is currently the most frequent
      non-AIDS-defining cancer in HIV-positive MSM, should be considered for this
      population. Moreover, vaccination strategies for the prevention of HPV infection
      should be taken into account.

PMID- 25397413
TI  - More safer sex intervention needed for HIV-positive MSM with higher education
      level for prevention of sexually transmitted hepatitis C.
AB  - INTRODUCTION: The epidemiology of hepatitis C virus (HCV) infections in Chinese
      HIV-infected men who have sex with men (MSM) remains obscure. More data is
      required to understand the epidemic and set up preventive strategy. MATERIALS AND
      METHODS: Baseline and annual testing of anti-HCV was in place for all HIV
      infected MSM in the largest HIV clinic in Hong Kong. Logistic regression was used
      to compare those with HCV seroconversion (seroconverters) with those remained
      tested anti-HCV negative (non-seroconverters) to identify factors associated with
      incident HCV. RESULTS: From 1999 to 2013, 1311 patients were tested for anti-HCV
      seroconversion, contributing to 6295 patient-years of observation. Fourteen
      (1.1%) patients seroconverted, with genotype 3 being most commonly detected. The
      overall incidence rate of HCV infection was 0.22 per 100 patient-years (PY) in
      the cohort. The incidence rate increased from 0.13 per 100PY before 2002 to 0.19
      per 100PY in 2002-2007 and 0.47 per 100PY in 2008-2013. All the seroconverters
      were Chinese, with median age of anti-HCV seroconversion at 38 years (range: 28
      53 years). None of them were injecting drug users. As compared with the non
      seroconverters, seroconverters were of higher education level (85.7% vs 50.7%
      tertiary education or above, OR 5.28, p=0.021) and had prior history of sexually
      transmitted infection (92.9% vs 60.9%, OR 8.34, p=0.041). More seroconverters
      were found to have history of syphilis infection (57.1% vs 37.2%, p=0.134) but
      the difference was not statistically significant. Baseline CD4 count and HIV
      viral load, proportion on antiretroviral therapy and duration of antiretroviral
      therapy were not different between two groups. CONCLUSIONS: The incidence of HCV
      has been increasing among HIV-infected MSM non-injecting drug users in Hong Kong.
      More education and intervention on safer sex is required to be targeted on those
      with higher education level.

PMID- 25397414
TI  - Facial emotional processing deficits in long-term HIV-suppressed patients.
AB  - INTRODUCTION: Emotional processing is basic for social behaviour. We examine for
      the first time the facial emotion processing in long-term HIV-suppressed
      patients. MATERIALS AND METHODS: Cross-sectional study comparing (ANOVA) six
      facial emotional processing tasks (two discrimination, two memory and two
      recognition) between HIV-suppressed patients (HIV+) on effective antiretroviral
      therapy (>2 years) and matched (age, gender) healthy controls (HCs). Accuracy in
      the recognition of basic emotions (neutral, happiness, sadness, anger and fear)
      in each recognition task was also compared (Mann-Whitney U test) between HIV+ and
      HCs. In the subset of HIV+, we evaluate which factors were associated with
      impaired recognition of basic emotions (accuracy below 50%) by multiple logistic
      regression analysis. Overall performance in all six emotional tasks were
      separately compared between neurocognitive impaired and non-impaired HIV+.
      RESULTS: We included 107 HIV+, mainly Caucasian (89%) male (72%) with a mean age
      of 47.4 years, neurocognitively non-impaired (75.5%), and 40 HCs. Overall
      discrimination (p=0.38), memory (p=0.65) and recognition tasks (p=0.29) were
      similar in both groups. However, HIV+ had lower sadness recognition in both
      recognition tasks and lower sadness, anger and fear recognition in the facial
      affect selection task (Figure 1). Only estimated pre-morbid functioning (WAIS-III
      R vocabulary subtest score) was significantly associated with sadness (1.99 [95%
      CI 1.18-3.58]; p=0.01) and anger recognition deficits (2.06 [95% CI 1.14-3.45];
      p=0.015) in the facial affect selection task. In HIV+ individuals, neurocognitive
      impairment was associated with worse memory task results (p<0.01, d=0.88; p<0.01,
      d=1.48). CONCLUSIONS: We did not find difference in the overall emotion
      processing between HIV+ and HIV- individuals. However, we found particular
      recognition deficits in the entire HIV+ sample. Estimated pre-morbid functioning
      was associated with sadness and anger recognition deficits in the facial affect
      selection task. Neurocognitive impaired HIV+ had additional memory deficits.
      These recognition deficits might conduct to social difficulties.

PMID- 25397415
TI  - Co-infections and co-morbidities among injecting drug users versus sexually
      infected patients in Bucharest.
AB  - INTRODUCTION: After the 2008 introduction of new psychoactive substances (NPS) in
      Romania, the number of newly diagnosed HIV infections showed significant increase
      among injecting drug users (IDUs). Our objective was to analyze the differences
      between co-infections related to the HIV infection, based on the way of
      transmission (IDUs versus sexually infected). MATERIALS AND METHODS: A
      retrospective transversal study was carried out, analyzing 245 adult HIV-positive
      patients, diagnosed between January 2013 and December 2013 in our hospital. We
      collected socio-demographic, epidemiological and laboratory data at the diagnosis
      and analyzed them using SPSS version 20. RESULTS: Most patients (71%, 174/245)
      were men and the median age was 32 years (IQR: 26-38). 91 patients (37%) were
      former/active IDUs (most of them injecting both opioids and NPS), while 154
      patients (63%) were sexually infected, with 84% being heterosexuals and 16% men
      having sex with men (MSM). The median CD4 count, at the moment of diagnosis, was
      294 cells/mm(3) (IQR: 119-483). CONCLUSION: Heterosexual transmission was the
      most common way of HIV transmission in 2013 in contrast with EU/CEE, where MSM
      accounted for the majority of cases of HIV epidemics in 2012 [1]. Sexually
      transmitted HIV infection was associated with late presentation, stage C and
      syphilis. We noted a high percentage of IDU transmission, which was associated
      with stage A and hepatitis C infection.

PMID- 25397416
TI  - Clinical and socio-demographic predictors for virologic failure in rural Southern
      Africa: preliminary findings from CART-1.
AB  - INTRODUCTION: In 2013, the World Health Organization (WHO) recommended scaling up
      of routine viral load (VL) monitoring for patients on antiretroviral therapy
      (ART) in resource-limited settings [1]. During the transition phase from no VL
      testing at all to routine VL-monitoring, targeted VL for groups at particular
      risk of virologic failure (VF) may be an option [2]. We present socio-demographic
      and clinical risk factors for VF in a cohort in rural Lesotho with no access to
      VL prior to the study. MATERIALS AND METHODS: Data derive from a cross-sectional
      study providing multi-disease screening as well as VL testing to adult patients
      (>=16 years old) on first-line ART >=6 months [3]. VF was defined as VL>=1000
      copies/mL. Assessed potential predictors of VF were: (1) socio-demographic (sex,
      age, wealth-quintile, education, employment status, disclosure of HIV status to
      environment, travel-time to facility); (2) treatment history (history of
      treatment interruption >2 days, previous drug substitution within first-line ART,
      time on ART, ART-base and -backbone); (3) adherence (pill count) and (4) clinical
      (clinical or immunological failure as defined by WHO guidelines [1], presence of
      papular pruritic eruption (PPE)). All variables with association to VF in
      univariate analysis were included in a multivariate logistic regression reporting
      adjusted Odds ratios (aOR). RESULTS: Data from 1,488 patients were analyzed.
      Overall VF-prevalence was 6.9% (95% CI 5.7-8.3). In univariate analysis, the
      following were associated with VF: age <30, lower wealth-quintile, no primary
      education, history of treatment interruption, nevirapine-base, zidovudine
      backbone, history of drug substitution, travel-time to clinic >=2 hours,
      disclosure of HIV status to <5 persons, clinical failure, presence of PPE and
      immunological failure. In multivariate analysis, 6 out of the above 12 variables
      were independent predictors: age <30 years (aOR: 2.4; 95% CI 1.1-5.3, p=0.029),
      history of treatment interruption (2.5; 1.3-4.7, p=0.005), PPE (6.9; 2.5-18.9,
      p<0.001), immunological failure (11.5; 5.7-23.2, p<0.001), history of drug
      substitution (1.9; 1.0-3.7, p=0.043), disclosure of HIV status to <5 persons
      (1.8; 1.1-3.1, p=0.03). CONCLUSION: In this cohort in rural Lesotho, several
      socio-demographic and clinical predictors were associated with VF. Particularly
      age <30 years, history of treatment interruption, PPE and immunological failure
      were strongly associated with VF. These patients may be prioritized for targeted
      VL-testing.

PMID- 25397417
TI  - Difference in factors associated with low-level viraemia and virological failure:
      results from the Austrian HIV Cohort Study.
AB  - INTRODUCTION: For some patients, it remains a challenge to achieve complete
      virological suppression which is the goal of antiretroviral therapy (ART).
      Identifying factors associated with low-level viraemia (LLV) and virological
      failure (VF) under ART might help to optimize management of these patients.
      MATERIALS AND METHODS: We investigated patients from the Austrian HIV Cohort
      Study receiving unmodified ART for >6 months with two nucleoside reverse
      transcriptase inhibitors (NRTIs) with either a non-nucleoside reverse
      transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) or an
      integrase inhibitor (INSTI) between 1 July 2012 and 1 July 2013 with at least one
      viral load (VL) measurement below the limit of detection (BLD) or below level of
      quantification (BLQ) in their treatment history. VF was defined as HIV-RNA levels
      >=200 copies/mL and all other quantifiable measurements were classified as LLV.
      Factors associated with LLV and VF compared to BLD and BLQ were identified by
      using logistic regression models. RESULTS: Of the 2,276 patients analyzed, 1,972
      (86.6%) were BLD or BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher
      risk for LLV and VF was found in patients with ART interruptions and in patients
      with boosted PI therapy. The risk for LLV and VF was lower in patients from a
      centre which uses Abbott RealTime HIV-1 assay compared to the other centres
      measuring VL by the Roche Cobas AmpliPrep/Cobas TaqMan 2.0. A higher risk for LLV
      but not for VF was found in patients with a higher VL before ART and shorter ART
      duration. A higher risk for VF but not for LLV was found in patients of younger
      age, originating from a high prevalence country, with a lower CD4 count and in
      male injecting drug users. CONCLUSIONS: This study of well-defined patients on
      stable ART over a period of more than six months gives insights into the
      different factors associated with LLV and VF. In patients with VF, factors
      associated with adherence play a prominent role, whereas in patients with LLV,
      the biology of viral replication comes additionally into effect. Despite its
      observational design, it has implications for patient management and forms the
      basis for future outcome studies.

PMID- 25397418
TI  - A retrospective observational study of low-level viraemia and its immunological
      and virological significance: which outcome to expect.
AB  - INTRODUCTION: Low-level viraemia (LLV) is observed in some patients with HIV-1
      infection on stable antiretroviral therapy (ART). The significance of these
      findings remains controversial as it conflicts with traditional optimal clinic
      outcome. This study aims to evaluate the effect of LLV on the establishment of
      virological failure (VF) and immune deterioration. METHODS: Retrospective
      observational study of a cohort of HIV-1 infected patients of an Infectious
      Diseases Clinic, who presented an HIV-1 viral load of 20 to 200 cp/mL, during the
      year 2012. Patients who were not on ART or non-adherent in the previous 6 months
      were excluded. Compliance was quantified by clinical and pharmaceutical records.
      Adherence was defined as >=95% compliance rate. Demographic, clinical,
      immunological and therapeutic data were collected from clinical records. LLV was
      defined as a range of 20-200 cp/mL and stratified as transient (T-LLV): only one
      measurement, persistent (P-LLV): 2 consecutive measurements with an interval >=3
      months and recurrent (R-LLV): >=1 T-LLV during an 18-month follow-up. Statistical
      analysis was performed with Microsoft Office(r) - Excel 2012. Kolmogorov-Smirnov
      test, t-test and chi-square test were performed for a significant p value <0.05.
      RESULTS: During 2012, 2161 HIV-1 infected patients were evaluated at our Clinic,
      93% of which were on ART. LLV was documented in 378 (19%), adherence was verified
      in 151 (52%). The analysis of this cohort (n=151) revealed: 77 (51%) T-LLV, 13
      (8.6%) R-LLV and 61 (40%) P-LLV. Mean viral load was 46 cp/mL. Mean TCD4 count
      was 665 cells/uL with a variation of +63 cells/uL during the study period. There
      was no VF documented. ART regimens were switched in 16 (11%) patients.
      Gastrointestinal disturbance was found in 13 (9%). Analysis showed no statistical
      differences between the analyzed variables (CD4 variation, time of diagnosis and
      treatment, duration of LLV persistence (less than or more than one year), number
      of ART regimens, ART regimen and type of NRTI backbone) for all groups (T-LLV, R
      LLV, P-LLV), except for mean viral load that showed significant superiority in
      the T-LLV(38 cp/mL) and R-LLV(36 cp/mL) vs P-LLV(58 cp/mL) (p=0.01 and p<0.01,
      respectively). CONCLUSIONS: The absence of significant differences in
      immunological and virological outcomes in this cohort and the absence of VF in
      all groups, suggests a scarce impact of LLV in patient's prognosis. Prospective
      studies, with longer follow-up could bring more accurate information.

PMID- 25397419
TI  - Longitudinal comparison of HIV-1 plasma viral load and cellular proviral load.
AB  - INTRODUCTION: The goal of antiretroviral treatment (ART) in HIV-1 infection is
      the permanent suppression of plasma viral load (pVL) below the currently existing
      limit of detection of 50 copies/mL (DAIG HIV-therapy guidelines). Therefore,
      treatment effectiveness is based on pVL. pVL measurements however do not give any
      information about the viral reservoir in peripheral blood mononuclear cells
      (PBMCs). Therefore, the proviral DNA of HIV-1 could be a useful marker for the
      investigation of viral reservoirs and monitoring ART in patients showing
      undetectable pVL. MATERIALS AND METHODS: Seventy-seven treatment-experienced HIV
      1 infected patients with pVL <50 copies/mL were randomly selected. pVL and
      proviral DNA load were measured using the Roche COBAS TaqMan HIV-1 v2.0 assay.
      Additionally, CD4+ cell count per mL and the total white blood cell (wbc) count
      per mL were determined for each patient. Follow-up data were collected 24 weeks
      after the time point of the first measurement. Proviral DNA load per mL, CD4+
      cell count per mL as well as wbc count per mL were observed over time and
      differences were estimated using the Mann-Whitney U test. Additionally,
      correlations between the clinical parameters were analyzed using the two-sided
      Pearson correlation analysis. RESULTS: Out of the 77 patients, 38 show a
      significant increase in proviral load per mL over time (p=0,001), whereas 39
      patients show a significant decrease (p=0,001). No differences became visible in
      the CD4+ cell count per mL comparing week 0 and week 24 data. Thirty five
      patients show a significant increase in wbc count per mL over time (p<0,001),
      while 42 patients show a significant decrease (p<0,001). A significant
      correlation of increasing proviral load per mL and wbc count per mL for data of
      the first (p<0.001) and the second measurement (p<0.001) can be detected, while
      there are no correlations found between proviral load per mL and CD4+ cell count
      per mL. CONCLUSIONS: Our data show that the presence of viral reservoirs in other
      cell types and not only CD4+ cells is most probable. HIV-1 proviral DNA seems to
      be an interesting marker in patients with undetectable pVL and allows the
      assessment of replication under ART. Nevertheless, further longitudinal studies
      are needed to assess the usefulness and the clinical significance of this marker.

PMID- 25397420
TI  - Analysis of transmitted drug resistance and HIV-1 subtypes using dried serum
      spots of recently HIV-infected individuals in 2013 in Germany.
AB  - INTRODUCTION: The Robert Koch Institute (RKI) aimed to assess a molecular
      surveillance strategy based on filter-dried serum spots (DSS) of all newly
      diagnosed HIV infections in Germany. In 2013, diagnostic laboratories sent DSS to
      the RKI representing 55% of the newly diagnosed HIV infections reported to the
      RKI (protection against infection act). DSS were first tested serologically to
      identify recently acquired infections (<140 days duration of infection); those
      classified as "recent infection" were processed for HIV-1 genotyping. The aim of
      this study was to assess the level of TDR and the current HIV-1 subtypes in the
      main HIV transmission group categories (TrGrpC) in 2013: men who have sex with
      men (MSM), women/men with heterosexual contacts (HET) and injecting drug users
      (IDUs). MATERIALS AND METHODS: DSS were tested for recency of infection using the
      BED capture EIA. Viral RNA from "recent infections" was amplified by HIV-1 group
      M generic pol-RT-PCR covering all resistance-associated positions in the HIV-1
      protease (AS1-99) and reverse transcriptase (AS1-252) if viral loads were >=6,500
      copies/mL. PCR amplicons were sequenced (Sanger) to analyze genotypic resistance
      and the HIV-1 subtype. RESULTS were merged to data from the HIV report, i.e. the
      TrGrpC. RESULTS: In 2013, 1027 DSS were classified as recent HIV infections (506
      MSM, 118 HET, 31 IDUs, 6 others, 366 unknown). RNA was extracted from 703 recent
      cases and 389/503 samples with sufficient viral load were PCR-positive. By June
      2014, 276/389 samples were sequenced: TDR was identified in 13% (35/276) of the
      recent infections including single (PI, NRTI, NNRTI) and dual drug class
      resistant strains (NRTI/NNRTI; NNRTI/PI). 18% (51/276) of recent HIV-1 infections
      were caused by non-B subtypes (A1, C, CRF01_AE, CRF02_AG, D, F, G, URFs). TDR was
      observed at comparable levels in all TrGrpC. Proportions of non-B infections were
      significantly higher in HET (78%; 14/18) and IDUs (60%; 3/5) compared to MSM (8%;
      14/169) (p<0.01). CONCLUSIONS: The proportion of TDR was similar but the
      proportion of HIV-1 subtype non-B infections was higher as previously described
      for Germany based on results from the German HIV-1 Seroconverter Cohort (1),2.
      This difference could be the result of a broadened inclusion of HET and IDUs due
      to the sampling method used making this study representative for molecular
      surveillance of HIV-1 in Germany.

PMID- 25397421
TI  - Comparison of routine versus targeted HIV testing strategies: coverage and
      estimated missed infections in emergency room and primary care centre.
AB  - INTRODUCTION: Different HIV Testing Strategies (TS) and clinical care settings
      had not been face to face evaluated (1). We compared coverage, Newly Diagnosed
      HIV Infection (NDHI) and Estimated Missing HIV Infections (MHI) in Hospital
      Emergency Room (HER) and Primary Care Center (PCC), in DRIVE study (Spanish
      acronym of HIV infection Rapid Diagnosis) and in clinical practice the year
      before DRIVE. MATERIALS AND METHODS: In DRIVE study, 18-60 years old, non-HIV
      infected population visiting an HER or a PCC were proposed both a structured risk
      practices and clinical conditions questionnaire (RP&CC-Q) and a rapid HIV test.
      This arm is the HIV Routine TS. We analyze a hypothetical arm, where risk
      practices were universally assessed with an RP&CC-Q, subsequently risk-positive
      patients where HIV tested, Targeted-TS. Coverage was assessed as the ratio of
      tested population (TP)/attended population (AP) in HER and PCC. TP/AP ratios were
      also calculated in the year before, the Clinical Practice-TS. NDHI was expressed
      per 0/00 tests performed. MHI was estimated assuming in the non-tested
      population, overall DRIVE rate of NDHI 0/00 and NDHI 0/00 in negative RP&CC-Q.
      RESULTS: A total of 5329 RP&CC-Q and rapid HIV tests were performed to 49.64%
      women, median age 37 (28-47) years old, mainly 74.9% Spaniards. Confirmed NDHI
      was 4.10/00, and in 48, 8% of RP&CC-Q negative NDH was 00/00. HIV screening
      coverage was always better in PCC than in HER, and higher in DRIVE study than in
      clinical practice. Estimated MHI was higher in HER and in the clinical practice
      TS. Targeted-TS coverage was lower, but resulted in similar NDHI and MHI than
      routine-TS, testing half the population, see Table 1. CONCLUSIONS: Best HIV
      Testing Strategy is routine-TS in Primary Care Center. Targeted-TS resulted in
      same newly HIV diagnoses and missed HIV infections than routine-TS with half the
      resources employed.

PMID- 25397422
TI  - Relationship between discordant response to HAART, Tregs, immune activation and
      low-level viraemia.
AB  - INTRODUCTION: The incomplete immune recovery upon effective long-term highly
      active antiretroviral therapy (HAART) has been associated with increased
      morbidity and mortality in HIV infected patients [1]. Immune cellular activation,
      Tregs or very low-level viraemia has been alternatively suspected, but never
      investigated simultaneously [2]. MATERIALS AND METHODS: We performed a cross
      sectional study in 87 aviraemic patients (men=62, mean CD4+T cells=570/mm(3),
      mean duration of HAART=12 years). Patients with at least 500 CD4+ T cells /mm(3)
      were classified as complete immunological responders (cIR), whereas remaining
      patients were classified as inadequate immunological responder (iIR). Tregs were
      characterized based on CD4+CD25highFoxP3+phenotype using a one-step intracellular
      staining. Effector Tregs and terminal effectors Tregs were respectively defined
      as CD4+CD25+FoxP3+CD45RA-, and CD4+CD25+FoxP3+CD45RA-HLADR+phenotypes as recently
      described [3]. Activated T cells were identified using (i) elevated HLA-DR
      expression for CD4+T cells, and (ii) increased expressions of HLA-DR, or CD38, or
      both (HLADR+CD38+cells) for CD8+T cells. Very low-level viraemia was defined as
      detectable viraemia between 1 and 39 cp/mL. Univariate and multivariate analyses
      were performed to identify determinants of iIR. RESULTS: Thirty-nine patients
      were classified as iIR, and 48 as cIR. Patients from the iIR group were
      significantly older (55 vs 50 years, p=0.027), and had percentages of activated
      CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs significantly
      higher (5.3 vs 4%, p=0.014; 9 vs 7.5%, p=0,022; 8 vs 6.3%, p=0.01 and 1.8 vs
      1.3%, p=0,033 among CD4+T cells, respectively). Neither the percentage of
      activated CD8+T cell nor very low-level viraemia were found to be associated with
      iIR. In the multivariate analysis, nadir of CD4+T cell count and percentage of
      Tregs were the only two parameters independently associated with iIR (OR=2.339,
      p=0.001, and OR=0.803, p=0.041, respectively). CONCLUSIONS: We present here the
      largest study investigating simultaneously immune response to long-term HAART,
      immune activation of CD4+ and CD8+ T cells, Tregs percentages and very low-level
      viraemia. Our results highlight the importance of Tregs in CD4 homeostasis. This
      aspect should now be prospectively explored in a large cohort of patients.

PMID- 25397423
TI  - Everything fine so far? Physical and mental health in HIV-infected patients with
      virological success and long-term exposure to antiretroviral therapy.
AB  - INTRODUCTION: Little is known about the well-being on long-term exposure to
      antiretroviral therapy. The ACTG Augmented Symptoms Distress Module (ASDM) is a
      validated tool which measures the presence of a total of 22 symptoms seen with
      HIV and quantifies the extent to which they cause distress to the patient.
      METHODS: ELBE was a cross-sectional study that consecutively included adult HIV
      infected patients presenting with viral suppression (<50 HIV RNA copies/mL) and
      ART exposure for at least five years. Patients were evaluated by four different
      questionnaires, including ASDM. RESULTS: Of a total of 894 patients included in
      the three participating ELBE centres, complete data on ASDM were available for
      698 patients (626 male, 69 female, 3 transsexual). Median age was 49.7 years
      (range, 23.3-82.5 years) and median exposure to ART was 11.5 years (range, 5-28
      years). Median CD4 T-cell counts had increased from a CD4 nadir of 180 to
      currently 640 cells/uL. Despite immunological and virological success, a high
      degree of symptom-related distress was noted in this patient population. In
      total, 63.8% and 36.3% of the patients had at least one "bothersome" or one "very
      bothersome" symptom, respectively. The symptoms most frequently reported to be
      "bothersome" or "very bothersome" were fatigue and energy loss (18.5% and 11.0%
      respectively), insomnia (12.8% and 11.6%), sadness and depression (13.0% and
      10.0%), sexual dysfunction (12.0% and 10.0%), and changes in body appearance
      (11.0% and 10.9%). There was no association between the degree of symptom-related
      distress and gender, age or CD4 T-cell nadir. However, the history of AIDS
      defining illnesses, comorbidities such as depression but also the duration of ART
      were significantly associated with a higher overall symptom summary score and
      with a higher frequency of symptoms. For example, in patients with at least 15
      years of ART exposure, only 27.3% of the patients did not report at least one
      "bothersome" or "very bothersome" symptom. CONCLUSIONS: In this large group of
      positively selected HIV+ patients with virological success and long-term exposure
      to ART, a high degree of symptom-related distress was found. Medical care of HIV
      infected patients should not only focus on optimal virological outcome. More data
      on quality of life in patients with long-term exposure to ART is needed.

PMID- 25397424
TI  - Accurate episomal HIV 2-LTR circles quantification using optimized DNA isolation
      and droplet digital PCR.
AB  - INTRODUCTION: In HIV-infected patients on combination antiretroviral therapy
      (cART), the detection of episomal HIV 2-LTR circles is a potential marker for
      ongoing viral replication. Quantification of 2-LTR circles is based on
      quantitative PCR or more recently on digital PCR assessment, but is hampered due
      to its low abundance. Sample pre-PCR processing is a critical step for 2-LTR
      circles quantification, which has not yet been sufficiently evaluated in patient
      derived samples. MATERIALS AND METHODS: We compared two sample processing
      procedures to more accurately quantify 2-LTR circles using droplet digital PCR
      (ddPCR). Episomal HIV 2-LTR circles were either isolated by genomic DNA isolation
      or by a modified plasmid DNA isolation, to separate the small episomal circular
      DNA from chromosomal DNA. This was performed in a dilution series of HIV-infected
      cells and HIV-1 infected patient derived samples (n=59). Samples for the plasmid
      DNA isolation method were spiked with an internal control plasmid. RESULTS:
      Genomic DNA isolation enables robust 2-LTR circles quantification. However, in
      the lower ranges of detection, PCR inhibition caused by high genomic DNA load
      substantially limits the amount of sample input and this impacts sensitivity and
      accuracy. Moreover, total genomic DNA isolation resulted in a lower recovery of 2
      LTR templates per isolate, further reducing its sensitivity. The modified plasmid
      DNA isolation with a spiked reference for normalization was more accurate in
      these low ranges compared to genomic DNA isolation. A linear correlation of both
      methods was observed in the dilution series (R2=0.974) and in the patient derived
      samples with 2-LTR numbers above 10 copies per million peripheral blood
      mononuclear cells (PBMCs), (R2=0.671). Furthermore, Bland-Altman analysis
      revealed an average agreement between the methods within the 27 samples in which
      2-LTR circles were detectable with both methods (bias: 0.3875+/-1.2657 log10).
      CONCLUSIONS: 2-LTR circles quantification in HIV-infected patients proved to be
      more accurate with a modified plasmid DNA isolation procedure compared to total
      genomic DNA isolation. This method enables the processing of more blood cells,
      thus enhancing quantification accuracy and sensitivity. An improved
      quantification of 2-LTR circles will contribute to the better understanding of
      ongoing replication in the HIV reservoir of patients on cART.

PMID- 25397425
TI  - Validation of an ultrasensitive digital droplet PCR assay for HIV-2 plasma RNA
      quantification.
AB  - INTRODUCTION: Low or undetectable plasma viral load (VL) using current qPCR
      assays is common for HIV-2 patients. Digital PCR is an emerging technology
      enabling more precision and reproducibility than qPCR at low DNA/RNA copy
      numbers. Available data related to digital droplet PCR (ddPCR, Bio-Rad)
      underscore issues linked to the threshold definition of positivity, coupled to
      the specificity of low copy results (1). MATERIALS AND METHODS: A RT-PCR protocol
      was set up using the One-Step RT-ddPCR Kit for Probes on the QX200 platform (Bio
      Rad, Hercules, CA) in an accredited environment (ISO15189:2012 norm). Parameters
      tested were in line with the digital MIQE guidelines (2). Inter-run coefficient
      of variation (CV) was established using synthetic RNA controls diluted in HIV
      negative plasma. The ddPCR assay was compared to a qRT-PCR previously used in
      routine (LOQ 50 cop/mL (3)) using 46 clinical samples and the NIBSC international
      HIV-2 RNA standard. RESULTS: The optimal PCR efficiency and the best separation
      between positive and negative droplets were obtained with a mixture containing
      0.5 mM manganese acetate, 700 nM primers and 250 nM of the 5'FAM-probe. Using a
      manual threshold to define positivity, 7.74% of negative controls (n=168) were
      scored as positive due to one positive droplet. The presence of two positive
      droplets or more was not observed for negative controls. Serial dilutions of a
      positive control showed excellent linearity (R2=0.999) and enabled us to define a
      limit of quantification of two positives droplets, which corresponds to 0.14
      copies/MUL in the reaction mixture and to seven copies per mL of plasma. The
      inter-run coefficient of variation was 3.37% at a mean value of 4,468 cop/mL,
      19.59% at 416 cop/mL and 32.28% at 8 cop/mL. The NIBSC standard of 1,000 IU was
      quantified 1,400 copies by ddPCR and close to 5,000 copies by qPCR (delta log
      superior to 0.5). Among 46 clinical samples, 22 were undetectable with both qPCR
      and ddPCR, 12 were detected with both methods (respective means of 10,612 and
      2,224 cop/mL, delta log=0.68) and 12 others were quantified by ddPCR only below
      50 cop/mL (mean=16 cop/mL). CONCLUSIONS: We validated a ddPCR HIV-2 VL assay that
      is more sensitive and more reproducible than the qPCR assay used as comparator,
      with a limit of quantification of 7 cop/mL of plasma. A careful definition of the
      limit of blank allows the management of false positive droplets, but the variable
      user-defined positive threshold may be an issue for compliance to the quality
      norms.

PMID- 25397426
TI  - Acute HIV infection (AHI) in a specialized clinical setting: case-finding,
      description of virological, epidemiological and clinical characteristics.
AB  - INTRODUCTION: Diagnosis of HIV infection during early stages is mandatory to
      catch up with the challenge of limiting HIV viral replication and reservoirs
      formation, as well as decreasing HIV transmissions by immediate cART initiation.
      OBJECTIVES: Aims were to describe (a) virological characteristics of AHI
      identified, (b) epidemiological and clinical factors associated with being
      diagnosed with AHI. METHODS: Cross-sectional, retrospective study. All
      individuals diagnosed with AHI according to Fiebig's staging between Jan 2013 and
      Mar 2014 at the INMI "L. Spallanzani" were included. Serum samples reactive to a
      fourth generation HIV-1/2 assay (Architect HIV Ag/Ab Combo, Abbott) were retested
      with another fourth generation assay (VIDAS DUO HIV Ultra, Biomerieux) and
      underwent confirmation with HIV-1 WB (New Lav I Bio-Rad) and/or with Geenius
      confirmatory assay (Bio-Rad). WHO criteria (two env products reactivity) were
      used to establish positivity of confirmatory assays. In case of clinically
      suspected AHI, HIV-1 RNA (Real time, Abbott) and p24 assay (VIDAS HIV P24 Bio
      Rad) were also performed. Avidity test was carried out, on confirmed positive
      samples lacking p31 reactivity, to discriminate between recent (true Fiebig V
      phase) and late infections; to avoid possible misclassifications, clinical data
      were also used. Demographic, epidemiological, clinical and laboratory data are
      routinely, and anonymously recorded in the SENDIH and SIREA studies. RESULTS:
      During the study period, we observed 483 newly HIV diagnosed individuals, of whom
      40 were identified as AHI (8.3%). Fiebig classification showed: 7 stage II/III,
      13 stage IV, 20 stage V. Demographic, epidemiological, and clinical
      characteristics of patients are shown in the Table. Overall, the study population
      had a median S/Co ratio at fourth generation EIA (Architect) of 49.50 (IQR, 23.54
      98.05): values were significantly lower in Fiebig II-IV than in Fiebig V (38.68
      [IQR, 20.08-54.84] vs 75.72 [IQR, 42.66-249.80], p=0.01). Overall, median HIV-1
      RNA was 5.44 log copies/mL (IQR, 4.29-6.18) and the value observed in Fiebig
      phase II-IV was higher than that found in Fiebig stage V (6.10 [IQR, 5.49-7.00]
      vs 4.69 [3.71-5.44], p<0.001). Median CD4+ cell count was 596/mmc (IQR, 410-737).
      cART was started in 26 patients: TDF/FTC/DRV/r/RAL=18; TDF/FTC/DRV/r=2;
      TDF/FTC/ATV/r=2; TDF+FTC+EFV=2; TDF/FTC/RAL=1; DRV/r+RAL=1. CONCLUSIONS:
      Integration of careful epidemiological investigation, partner notification, and
      technical advances in virological testing are key elements in AHI case-finding.
      Significant differences were found between Fiebig stages II-IV and Fiebig V with
      regard to virological exams.

PMID- 25397427
TI  - Service impact of a change in HIV-1 viral load quantification assay.
AB  - INTRODUCTION: Due to discontinuation of the Siemens Versant HIV-1 RNA (bDNA)
      assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV
      1 viral load (VL) assay (Roche) in April 2013. This assay has a lower cut-off of
      20 RNA copies/mL (compared with <50 for the Siemens assay). Our laboratory
      demonstrated previously that a significant proportion (18%) of patients
      undetectable using bDNA HIV-1 RNA quantification exhibited low level viraemia
      (LLV) using the new assay. Local guidelines recommend that patients stable on
      therapy receive twice-yearly VLs. We evaluated the impact of the introduction of
      the new assay on our clinical service. METHODS: A retrospective cohort analysis
      of treated patients with stable undetectable VL by bDNA (<50 copies/mL) followed
      by >= one low-level (<400 copies/mL) VL with the Roche assay. Demographic data
      were collected in addition to frequency of VL testing and genotypic resistance
      assays. Referrals to virtual clinic (VC) were recorded. Patients were identified
      using laboratory data and information collected from electronic patient records.
      RESULTS were analyzed with SPSS v18. RESULTS: One hundred and ninety patients
      were included. DEMOGRAPHICS: 79.5% male; 60.6% homosexual; mean age of 46 years.
      Duration on stable treatment was 46.35 (std. dev. 38.15) months. Current
      treatment regimens were 43.3% PI-based; 43.3% NNRTI-based and 13.7% other.
      Patients were stratified into VL 20-49 copies/mL (n=109); VL 50-199 copies/mL
      (n=71) and VL 200-399 copies/mL (n=10). In total, there were 471 VLs measured of
      which 274 were additional as a result of the assay switch. This resulted in six
      HIV-1 genotype requests and 16 VC discussions (Table 1). Longer duration on HAART
      was associated with reduced frequency of VL testing. The relative risk of ongoing
      detectability according to drug class are: PI 1.62 (95% CI 1.18-2.21); NNRTI
      0.507 (95% CI 0.30-0.85) and other 1.09 (95% CI 0.48-2.43). CONCLUSIONS: Changes
      in assay can result in difficulties in interpretation of patient results. The
      assay switch in our service had significant impact on patient and staff time and
      cost with an increase in patient recalls; increased frequency of VL measurement,
      genotypes and discussions in VC. Choice of assay is paramount to running an
      efficient and cost-effective clinical service.

PMID- 25397428
TI  - Outcomes of initial antiretroviral treatment (ART) among recently diagnosed HIV
      patients in HIV-TR cohort, 2011-2012.
AB  - INTRODUCTION: HIV-TR is a recently established (2012) multicentre cohort in
      Turkey. The aim of this study is to analyze epidemiological, immunologic and
      virologic data of recently diagnosed HIV patients. MATERIALS AND METHODS:
      Epidemiologic, clinical and laboratory data of all patients diagnosed in 2011 and
      2012 were recorded by a web-based data collection system, retrospectively.
      RESULTS: A total of 693 patients (561 male, 132 female) at 24 sites were
      enrolled. The median age at first presentation for HIV care was 36. The
      proportion of patients presenting with advanced HIV disease (CD4 count<200/mm(3)
      or presenting with an AIDS-defining event) was 30.6%; and 52.4% of patients were
      late presenters (CD4 count<350/mm(3) or presenting with an AIDS-defining event).
      Median CD4 counts at presentation and before treatment were 344 (IQR: 175-540)
      and 295 (IQR: 150-430), respectively. Pretreatment CD4 count was >500 copies/mL
      in 18.5% of patients. Of 531 patients receiving ART, initial combinations consist
      of tenofovir/emtricitabine (TDF/FTC) plus efavirenz (EFV) in 48.2% and TDF/FTC
      plus lopinavir/ritonavir (LPV/r) in 37.5% and other combinations in 14.3% of the
      patients. Pre-treatment HIV-RNA was over 100.000 copies/mL in 52.3% of patients.
      At Weeks 24 and 48, HIV-RNA were<50 copies/mL in 63,4% of 385 patients and 82% of
      311 patients reported to be still on ART and had a viral load measurement,
      respectively. Median pretreatment CD4 count was lower for TDF/FTC+LPV/r
      recipients than TDF/FTC+EFV recipients (250 vs 316) (p<0.05). The median increase
      from baseline CD4 cell count was 230 in TDF/FTC+LPV/r group, 193 in TDF/FTC+EFV
      group and 216 among all treated patients. Of 531 patients receiving ART, 11 had
      died and 19 were lost to follow-up. CONCLUSION: Despite 52.4% of recently
      diagnosed patients were late presenters; a high rate of virologic suppression was
      achieved in HIV-TR Cohort. A national HIV testing strategy targeting
      subpopulations with higher risk is urgently needed.

PMID- 25397429
TI  - Structural-equation-modelling of the tropism impact on achieving viral
      suppression within six months in naive HIV patients.
AB  - INTRODUCTION: Aim of the study was to evaluate the relevance of baseline (BL)
      plasma tropism of HIV on the achievement of a viral suppression within six months
      of antiviral therapy (ARV) in naive patients by a structural-equation-modelling.
      MATERIALS AND METHODS: Two-hundred and twenty-seven patients were enrolled; viral
      tropism on plasma was determined at baseline (BL) by sequencing and
      interpretation by genotopheno algorithm. Booster atazanavir or lopinavir , or
      efavirenz or nevirapine were used, in combination with either abacavir/lamivudine
      or tenofovir-emtricitabine. RESULTS: X4-tropism correlate negatively with CD4
      cell count at BL and follow-up (FU), and CD4 correlate negatively with BL-plasma
      viremia (PLV). BL-PLV correlate positively with FU-PLV. We have developed the
      hypothesis that the variables BL-CD4 and BL-PLV represent a mediators chain among
      X4-tropism and outcome of plasma viraemia at six months. This model, after
      structural-equation-modelling (SEM, Stata13), is shown in Figure 1. The indirect
      effect of X4-tropism on Fup-PLV is significant (p<0.01) but about 10 fold lower
      than the direct effect by BL-PLV. X4-tropism also has a direct negative effect on
      BL-CD4 (p<0.001) and an indirect positive effect on BL-PLV (p<0.001),
      irrespective of the drug regimen. Path model explaining direct and mediated
      effects of "tro (tropism)," "gender," "age," "cd0 (BL-CD4)" and "lrna0 (BL-PLV)"
      on the final outcome ("lrna1-Fup-PLV)," where "tro," "gender," and "age" are
      exogenous, cd0 and lrna0 are endogenous (mediators). Numbers on the arrows
      indicate direct effects. Circles indicate residuals related to
      endogenous/dependent variables; numbers near to circles are the corresponding
      variances. CONCLUSIONS: This model shows the relevance of BL-tropism on the
      outcome of plasma viraemia in naive patients after six months of therapy,
      irrespective of drug regimen used.

PMID- 25397430
TI  - The absolute lymphocyte count accurately estimates CD4 counts in HIV-infected
      adults with virologic suppression and immune reconstitution.
AB  - INTRODUCTION: The clinical value of monitoring CD4 counts in immune
      reconstituted, virologically suppressed HIV-infected patients is limited. We
      investigated if absolute lymphocyte counts (ALC) from an automated blood counting
      machine could accurately estimate CD4 counts. MATERIALS AND METHODS: CD4 counts,
      ALC and HIV viral load (VL) were extracted from an electronic laboratory database
      for all patients in HIV care at the Communicable Diseases Centre, Tan Tock Seng
      Hospital, Singapore (2008-13). Virologic suppression was defined as consecutive
      HIV VLs <400 days apart, <200 copies/mL. CD4 counts and same day ALCs were
      collected during virologic suppression from the first CD4> 300 cells/mm(3). CD4
      counts were estimated using the CD4% from the first value >300 and an ALC 181-540
      days later. RESULTS: A total of 1215 periods of virologic suppression were
      identified from 1183 patients, with 2227 paired CD4-ALCs available for analysis.
      98.3% of CD4 estimates were within 50% of the actual value. 83.3% within 25% and
      40.5% within 10%. The error pattern was approximately symmetrically distributed
      around a mean of -6.5%, but significant peaked and with mild positive skew
      (kurtosis 4.45, skewness 1.07). Causes for these errors were explored.
      Variability between lymphocyte counts measured by ALC and flow cytometry did not
      follow an apparent pattern, and contributed to 32% of the total error (median
      absolute error 5.5%, IQR 2.6-9.3). The CD4% estimate was significantly lower than
      the actual value (t-test, p<0.0001). The magnitude of this difference was greater
      for lower values, and above 25%, there was no significant difference. Precision
      of the CD4 estimate was similar as baseline CD4% increased, however accuracy
      improved significantly: from a median 16% underestimation to 0% as baseline CD4%
      increased from 12 to 30. Above a CD4% baseline of 25, estimates of CD4 were
      within 25% of the actual value 90.2% of the time with a median 2%
      underestimation. A robust (bisqaure) linear regression model was developed to
      correct for the rise in CD4% with time, when baseline was 14-24 (coefficients:
      intercept=3.30, CD4=0.939). This improved accuracy from 82.0% to 85.4%, and
      median error from 11% underestimation to 1% (p<0.0001). Adding time since
      baseline CD4% into the model increased complexity without significantly improving
      accuracy. CONCLUSION: In virologically suppressed hosts with CD4 >=300
      cells/mm(3) and percentage >=14, CD4 counts can be predicted with 85-90%
      confidence to within 25% of the actual value using the ALC.

PMID- 25397431
TI  - The effect of tenofovir in renal function in HIV-positive adult patients in the
      Roma health service area, Lesotho, southern Africa.
AB  - INTRODUCTION: The government of Lesotho introduced tenofovir disoproxil fumarate
      (TDF) for first-line antiretroviral treatment (ART), as recommended by the World
      Health Organization (1), in 2008. The use of TDF has been associated with renal
      toxicity (2); furthermore, renal function outcomes following the use of TDF has
      not been studied at Roma Health Service Area (RHSA) in Lesotho. Lesotho is a
      small landlocked country surrounded by South Africa. The study used an analytical
      design to compare retrospective creatinine clearance (CrCl) data of 312 (64%)
      antiretroviral treatment naive adults exposed to TDF and 173 (36%) unexposed
      patients. METHODS: Impaired renal function was defined as CrCl less than 50
      mL/min calculated using the Cockcroft-Gault equation. The Ministry of Health and
      Social Welfare of Lesotho approved the study on 13 January 2012. The study
      included adult (excluding pregnant females) HIV patients enrolled on ART between
      December 2006 and December 2012 at St Joseph's Mission Hospital and at Nazareth
      Health Centre (RHSA). Patients at Nazareth Health Centre and at St Joseph's
      Mission Hospital made up 80% of the circa 4 116 HIV patients on ART. Only 485
      patients met the set inclusion criteria. RESULTS: In 56 patients (17.9%), TDF was
      found to be contraindicated. The use of TDF was marginally significant factor for
      renal toxicity (p=0.054) in univariate analysis, but was insignificant (p=0.122)
      in multivariate logistic analysis. Univariate (p<0.1) and multivariate logistic
      regression (p<0.05) were performed using STATA((r)) 11. Female gender (p=0.016),
      hypertension (p=0.009), and age>60 (p=0.004) were significantly associated with
      CrCl<50 mL/min outcome. CONCLUSIONS: In this study, TDF proofed to be a weak
      contributing factor of renal impairment. Routine baseline renal function
      screening should however be adopted to prevent patients with impaired renal
      function receiving TDF.

PMID- 25397432
TI  - Monitoring of the lactonase activity of paraoxonase-1 enzyme in HIV-1-infection.
AB  - Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme known
      as a free radical scavenging system (1). PON-1 has three main activities,
      responsible for its antioxidant and anti-inflammatory potential: paraoxonase,
      arylesterase and lactonase (LACase), the latest to be discovered and pointed out
      to be its native activity (2). Among other physiological roles, the LACase might
      minimize the deleterious effects of hyperhomocysteinaemia in infection, by
      detoxifying the highly reactive metabolite homocysteine-thiolactone (HcyTL)
      (3),4. In the present work, we have developed and applied a method to quantify
      LACase activity and to explore the role of this enzyme in HIV-infection and
      virological response. The LACase activity was monitored in a cohort of HIV-1
      infected patients, through the titration of 3-(o-hydroxyphenyl) propionic acid,
      formed upon the LACase-mediated hydrolysis of the substrate dihydrocoumarin. The
      study protocol was approved by the Ethics Committee of Centro Hospitalar de
      Lisboa Central and Hospital Prof. Doutor Fernando Fonseca. All patients gave
      their written informed consent and were adults with documented HIV-1-infection,
      regardless of combined antiretroviral therapy (cART) use. Naive patients and
      patients who had received continuous antiretroviral treatment for more than one
      month were included. A total of 179 HIV-1-infected patients were included on this
      study (51% Men, 39% non-Caucasian, 45+/-13 years old). Patients with non
      suppressed viraemia, either from the non-cART (n=89, 12+/-4 kU/L, p<0.01) or from
      the cART with detectable viral load (n=11, 10+/-5 kU/L, p<0.05) groups, had lower
      activity than the cART with suppressed viraemia (n=79, 15+/-7 kU/L) (Kruskal
      Wallis test). Among naive patients, higher viral load (> 31,500 cps/mL, Spearman
      r=-0.535, p=0.003) and lower CD4+ T-cells count (< 500 cell/mm(3), Pearson
      r=0.326, p=0.024) were associated with the LACase activity. The present study
      suggests that lower LACase activity is associated with uncontrolled HIV-1
      infection, particularly with non-suppressed viraemia, despite of cART. This data
      seems to point to LACase role in HIV-infection, probably reflecting an increased
      formation of HcyTL deleterious species. A better knowledge of the LACase and its
      role in HcyTL pathophysiology might identify new therapeutic targets in HIV-1
      infected patients. Acknowledgements: EXPL/DTP-FTO/0204/2012; EXPL/DTP
      PIC/1758/2013. 

PMID- 25397433
TI  - Characterization of HIV-1 subtypes in a Portuguese cohort.
AB  - INTRODUCTION: Distribution of HIV-1 subtypes is variable around the world, with
      the most common subtype in western Europe being subtype B. The aim our study was
      to describe the prevalence of different HIV-1 subtypes in newly diagnosed
      patients and identify demographic and epidemiological characteristics related
      with different subtypes. MATERIALS AND METHODS: Retrospective single-centre study
      of patients newly diagnosed with HIV-1 infection between 2006 and 2012.
      Epidemiological data was gathered and genotyping was performed in each patient
      identified. Demographic and epidemiological characteristics were compared between
      patients with subtype B and other subtypes. Continuous variables were summarized
      by mean and standard deviation whereas categorical variables were presented as
      proportions. Comparison of groups was performed using the Chi square, Fisher
      exact test and Student T test. Statistical significance was assumed when p<0.05.
      RESULTS: In the period of the study, 624 patients newly diagnosed with HIV-1
      infection were submitted to genotypic testing but information about subtype was
      available only for 592 patients. General characteristics of the patients are
      summarized in Table 1. The distribution of the identified subtypes was the
      following: 286 (48.3%) patients had subtype B, 157 (26.5%) had subtype G, 54
      (9.1%) had subtype C, 36 (6.1%) had subtype A, 32 (5.4%) had subtype F and 25
      (4.2%) had CRF's. Patients with subtype B were more commonly male (p=0.001) and
      younger (p<0.0001) than those with subtypes other than B. Subtype B was more
      common in MSM patients, while non-B subtypes were more common in heterosexual
      patients and in injecting drug users (p=0.001). CD4-cell count, viral load and
      AIDS at presentation were not significantly different between subtypes.
      Resistance associated mutations were significantly more common in patients with
      non-B subtypes (15.4% vs 9.8%; p=0.048). CONCLUSIONS: The most commonly
      identified subtype was B in accordance with previous reports from other western
      European countries. However, in our cohort the proportion of non-B subtypes is
      higher than that reported for other European countries, probably reflecting the
      influence of strong bonds with Portuguese speaking African countries. Knowledge
      about HIV subtypes distribution may help understanding transmission dynamics and
      can be an important tool in the design of preventive measures.

PMID- 25397434
TI  - Molecular epidemiology of HIV-1 strains in Antalya, Turkey.
AB  - INTRODUCTION: The aim of this study was to determine the subtype distribution of
      HIV-1 strains isolated from antiretroviral therapy (ART)-naive and on treatment
      patients in Antalya, the city of southern Turkey. MATERIALS AND METHODS: The
      study included 77 of 92 newly diagnosed HIV-1 positive patients of last two years
      (between February 2012 and June 2014). HIV-1 subtypes and circulating recombinant
      forms (CRFs) were identified by phylogenetic analysis of reverse-transcriptase
      (codon 41-238) and protease (codon 1-99) domains (~667 bp) of pol gene region in
      HIV-1 strains. RESULTS: Subtype B (48%, 37/77) was identified as the most common
      HIV-1 subtype in Antalya that similar the other Turkish patients. Non-B subtypes
      were followed as CRFs (39%, 30/77). Interestingly, CRF14_BG (12.9%, 10/77) was
      found for the first time in Antalya in contrast to previous observations in the
      other reports in Turkey. Also, subtype G (6.5%, 5/77) was detected more often
      than HIV-1 subtypes in circulation of Turkey. CONCLUSIONS: These findings may be
      associated with specific geographic localization of Antalya that touristic
      movements of city. Recognized HIV-1 subtype diversity is major challenges in the
      development of a globally effective HIV vaccine.

PMID- 25397435
TI  - Plasma HIV-1 tropism and risk of short-term clinical progression to AIDS or
      death.
AB  - INTRODUCTION: It is uncertain if plasma HIV-1 tropism is an independent predictor
      of short-term risk of clinical progression / death, in addition to the CD4 count
      and HIV RNA level. We conducted a nested case-control study within EuroSIDA to
      assess this question amongst people with current HIV RNA level >1000 copies/mL,
      including both people on ART and those ART naive. METHODS: People with an AIDS
      diagnosis or who died from any causes for whom there was a stored plasma sample
      with HIV-1 RNA (VL)>=1,000 copies/mL available in the time window of 3-12 months
      prior to the event were identified. At least one control was selected for each
      case matched for age, VL and HCV status at the time of sampling. Controls were
      event-free after a matched duration of time from the date of sampling. Plasma HIV
      tropism was estimated using 454 and population sequencing (PS). Non-R5 HIV was
      defined as: (a) >=2% of sequences with a Geno2Pheno (G2P) FPR<=3.75% by 454, and
      (b) a G2P FPR<=10% by PS. We also compared CD4 slopes over the 12 months
      following the date of sampling using a linear mixed model with random intercept
      according to HIV tropism and ART status. RESULTS: The study included 266
      subjects, 100 cases and 166 controls, with sample taken on average in 2006; 23%
      and 24% had non-R5 HIV by 454 and PS respectively. There were 19% women, 25% MSM,
      92% Caucasians, 22% HCV+. At the time of sampling, 26% were ART-naive, 25% had
      started but were off ART and 49% were receiving ART. The median age, CD4 and
      viral load was 41 years, 350 cells/mm(3) and 4.81 log c/mL, respectively.
      Baseline characteristics were well balanced by tropism. Factors independently
      associated with clinical progression or death were female gender (OR=2.12; 95%
      CI=1.04, 4.36; p=0.038), CD4+ count (OR=0.90 per 100 cells/mm(3) higher; 95% CI
      0.80, 1.00; p=0.058), being on ART (OR=2.72; 95% CI 1.15, 6.41; p=0.022) and
      calendar year of sample (OR=0.84 per more recent year; 95% CI=0.77, 0.91;
      p<0.001). Baseline plasma tropism was not an independent risk factor for clinical
      progression or death by either 454 or PS. No significant interaction was observed
      between tropism and ART status. There were no significant differences in the CD4+
      slope within or between tropism groups. CONCLUSIONS: Plasma HIV-1 tropism does
      not appear to add to the ability of CD4 count and viral load to predict the short
      term risk of AIDS and death outcomes, even with 454 sequencing.

PMID- 25397436
TI  - Using dried blood spots collected under field condition to determine HIV-1
      diversity and drug resistance mutations in resource limited Tanzania.
AB  - INTRODUCTION: A dried blood spot (DBS) on filter paper has been used for
      different tests globally and has gained popularities in resource limited settings
      especially during HIV/AIDS epidemic. We assessed the efficiency of molecular
      characterization of HIV-1 subtypes using DBS collected under field conditions in
      northern Tanzania. MATERIALS AND METHODS: In 2011 and 2012, 60 DBS samples were
      collected under field conditions from exposed and newly diagnosed HIV-1 infected
      children from Kilimanjaro (n=20), Arusha (n=20), Tanga (n=10) and Manyara (n=10).
      RESULTS AND DISCUSSION: Of 60 DBS analyzed at both Protease (PR) and Reverse
      Transcriptase (RT) regions, 45 (75%) were analyzed, including 17 (85%) from
      Kilimanjaro, 15 (75%) from Arusha, 8 (80%) from Tanga, and 5 (50%) from Manyara
      region. All 45 DBS characterized had viral load above 1000 copies/mL with mean
      log10 viral loads of 3.87 copies/mL (SD 0.995). The phylogenetic results
      indicated presence of subtype and circulating recombinant form (CRF). In which,
      24 were subtype A1 (53.33%), 16 were subtype C (35.55%), 3 were subtype D (6.67%)
      and 2 were CRF10_CD (4.35%). All major mutations were detected in the RT region,
      none from protease (PR) region. The mutations detected were Y181C (n=8), K103
      (n=4) and G190A (n=1), conferring resistance to non-nucleoside reverse
      transcriptase inhibitors (NNRTIs), and M184V (n=1), conferring resistance to
      lamivudine and emtricitabine. CONCLUSIONS: Our results indicate that DBS
      collected from field conditions in resource scarcity areas can be used to
      determine the phylogeny of the virus and drug resistance mutations in areas with
      diverse HIV-1 group M subtypes.

PMID- 25397437
TI  - Temporal increase in HIV-1 non-R5 tropism frequency among antiretroviral-naive
      patients from northern Poland.
AB  - INTRODUCTION: Sequencing of the third hypervariable loop allows to identify
      genotype-based HIV tropism. R5-tropic viruses associated with early stages of
      infection are preferentially transmitted, while non-R5 HIV-1 tropism has been
      associated with severe immunodeficiency and lower lymphocyte CD4 nadir and may
      reflect delayed HIV diagnosis. In this study, we investigate the changes in
      tropism frequency from 2007 to 2013. MATERIALS AND METHODS: Study included 194
      patients with confirmed HIV infection linked to care in 2007-2013. Baseline
      plasma samples from treatment naive patients were used for HIV-1 genotypic
      tropism assessment based on triplicate V3 loop sequencing. Non-R5 tropism
      prediction thresholds were assigned using a false positive rate (FPR) of 10% and
      5.75% FPR and associated with clinical and laboratory data (age, gender, date of
      HIV diagnosis, route of transmission, CDC clinical category at diagnosis,
      pretreatment HIV viral load, baseline and nadir lymphocyte CD4 counts). For
      statistics, chi-square and Mann-Whitney U tests were used, time trends were
      examined using logistic regression (R statistical platform, v. 3.1.0) for binary
      variables and linear regression for continuous ones. RESULTS: Overall non-R5
      tropism frequency for the 5.75% FPR was 15.5% and 27.8% for 10% FPR. Frequency of
      the non-R5 tropism predicted using 5.75% FPR increased significantly from 2007
      (0%) to 2013 (25%) [OR: 1.44 (95% CI 1.14-1.86), p=0.003, rough slope
      +3.89%/year] (Figure 1a). With 10% FPR, the frequency changed from 7% (2007) to
      33% (2013) [OR: 1.17 (95% CI 0.99-1.39), p=0.054, rough slope +3.0%/year] (Figure
      1b). Baseline lymphocyte CD4 count and nadir, as well as pretreatment HIV-1 viral
      loads were stable over time of observation (r=0.014, p=0.84; r=0.13, p=0.085;
      r=0.016, p=0.83 for CD4 baseline, nadir and HIV load, respectively). Frequency of
      AIDS at HIV diagnosis increased from 21.4% in 2007 to 38.0% in 2013, however
      trend over time was insignificant [OR: 1.1 (95% CI 0.95-1.31), p=0.19]. Temporal
      trends for HIV transmission route, gender, non-B variant frequencies also were
      not significant. CONCLUSIONS: R5 tropism predominates among the treatment naive
      individuals but increase in the frequency of non-R5 tropic variants may limit
      clinical efficacy of the coreceptor inhibitors. Increased prevalence of non-R5
      HIV-1 may be related to late care entry and higher number of AIDS diagnoses in
      the recent years.

PMID- 25397438
TI  - Evolution trends over three decades of HIV infection late diagnosis: the
      experience of a Portuguese cohort of 705 HIV-infected patients.
AB  - INTRODUCTION: Late HIV diagnosis is common and associated with an increased risk
      of clinical progression, blunted immune response on antiretroviral (ARV) therapy
      and higher risk of drug toxicity. Across Europe, more than a third of patients
      are diagnosed late and consequently delay medical care. European Consensus
      definition group identify as late presentation (LP) persons, presenting for care,
      with a CD4 count below 350 cell/mm(3) or presenting with AIDS-defining event,
      regardless of CD4 cell count. Additionally, advanced HIV disease (AD) is defined
      by a CD4 count below 200 cell/mm(3) or an AIDS defining condition in persons
      presenting to care. MATERIALS AND METHODS: Retrospective observational study of a
      cohort of 705 HIV-infected patients diagnosed between 1986 and 2014 and medically
      followed at an Infectious Diseases Service in Lisbon. OBJECTIVES: Evaluate LP
      rate evolution in the last three decades (10-year time intervals considered: 1986
      1995; 1996-2005; 2006-2014); compare clinic, immunologic, virologic and
      therapeutic response over time. Identify main reasons responsible for late HIV
      diagnosis in order to promote optimized intervention strategies. SPSS version
      20.0 was used for statistical analysis. RESULTS: Study included 705 patients HIV
      diagnosed during 3 time intervals: group A n=82 [1986-1995]; group B n=332 [1996
      2005]; group C n=291 [2006-2014]. Demographic and epidemiological
      characterization revealed (A vs B vs C): male predominance of 79% vs 66% vs 66%;
      mean age at diagnosis 30 vs 36 vs 42 years; Portugal (82% vs 70% vs 58%) and
      Africa (13% vs 23% vs 29%) as the main places of birth; transmission by
      heterosexual contact in 21% vs 47% vs 62%, MSM in 21% vs 15% vs 23% and IVDU in
      57% vs 35% vs 13%. Mean CD4 at diagnosis was 362 vs 344 vs 377 cell/mm(3).
      Considering the time intervals, LP was found in 52% vs 56% vs 52% of patients and
      AD in 31% vs 38% vs 35%, respectively. At first health care encounter, 46% vs 43%
      vs 39% of individuals presented with AIDS. Over follow up, the vast majority
      initiated ARV (95% vs 98% vs 84%) and mean CD4 at that time was 254 vs 282 vs 250
      cell/mm(3). The last immunologic and virologic determination available registered
      mean CD4 of 657 vs 644 vs 584 cell/mm(3) and undetectable HIV plasma RNA in 92%
      vs 84% vs 82% of treated patients. CONCLUSIONS: This study evidenced a maintained
      LP rate, slightly above 50% in each of the three analyzed last decades, and one
      third of patients presented AD at HIV diagnosis. At initial health care contact,
      nearly 40% of individuals met AIDS clinical or immunological criteria.

PMID- 25397439
TI  - Intermittent viraemia and immune reconstitution in patients with more than 10-15
      years of antiretroviral therapy: baseline values still matter.
AB  - INTRODUCTION: Data on patients with long-term exposure to ART is scarce because
      controlled studies usually do not follow up patients for more than five to seven
      years. We were interested whether baseline parameters such as CD4 T-cell nadir or
      pre-treatment viraemia do have an impact on ART success after more than a decade
      of treatment. METHODS: ELBE is a cross-sectional study on adult HIV+ patients
      presenting consecutively with viral suppression (<50 HIV RNA copies/mL) and with
      ART exposure of at least five years. In this sub-analysis, all patients with more
      than 10 years of ART exposure were evaluated for immune reconstitution and for
      intermittent transient viraemia (50-1000 copies/mL, defined as "blips") during
      the last five years. RESULTS: From a total of 894 patients included in the three
      participating ELBE centres, 524 patients had an ART exposure of at least 10 years
      and had been treated continuously during the last 5 years. Of these, 33.4% had at
      least one "blip" while 63.5% did not show any transient viraemia of more than 50
      copies/mL. Patients with at least one blip had a higher pre-treatment viraemia
      compared to patients without blips (5.30 versus 5.06 log copies/mL, p=0.0003). In
      patients with a pre-treatment viraemia of more than 100,000, 50,000-100,000 and
      less than 50,000 copies/mL, the proportions of patients with blips during the
      last five years were 39.5%, 30.5% and 21.8% (p=0.007), respectively. The history
      of an AIDS-defining illness or the CD4 T-cell nadir was not associated with a
      higher frequency of blips. However, CD4 T-cell nadir was a strong predictor for
      current CD4 T-cell counts. In patient groups with a CD4 T-cell nadir of 0-99, 100
      199, 200-349, 350+ cells/uL, the median current CD4 T cells were 571, 667, 710
      and 890 cells/uL, respectively. These differences remained significant when the
      analysis was restricted to patients with more than 15 years of ART exposure
      (n=268). CONCLUSIONS: In this large group of positively selected HIV+ patients
      with long-term exposure to ART of at least 10-15 years, high pre-treatment
      viraemia was still associated with a higher frequency of intermittent transient
      viraemia ("blip"). A low CD4 T-cell nadir remained associated with a lower CD4
      cell recovery. The clinical implications of these findings remain to be
      evaluated.

PMID- 25397440
TI  - Characteristics of late presentation of HIV infection in MSM and heterosexual
      adults in Portugal 2011-2013.
AB  - INTRODUCTION: It is estimated that over half of newly diagnosed HIV infections in
      Europe present late. An HIV positive individual presenting late to care
      represents a missed opportunity to benefit from treatment, increasing the risk of
      morbidity and mortality at an individual level, and onward disease transmission
      at population level. Reducing late presentation is a strategic priority of the
      Portuguese HIV/AIDS program. We set out to describe the characteristics of late
      presentation in the two largest transmission risk groups currently in Portugal to
      inform HIV prevention and treatment. METHODS: We extracted details of all
      notified cases from individuals over 15 years with a laboratory confirmed HIV
      diagnosis made between January 2011 and December 2013 from the Portuguese HIV
      surveillance database and selected cases from heterosexuals and men who have sex
      with men (MSM). We defined late presentation as an initial CD4 count <350
      cells/mm(3) or presence of AIDS-defining disease at time of HIV diagnosis. We
      calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) for
      characteristics associated with late presentation in separate logistic regression
      for heterosexuals and MSM. RESULTS: Of 4219 HIV positive cases notified, 2589
      (61%) were heterosexuals and 1220 (29%) were MSM. A total of 1586 (38%) cases
      presented late of which 1037 (40%) were heterosexual and 328 (27%) were MSM. The
      median age at late presentation was 40 in heterosexual women, 46 in heterosexual
      men and 35 in MSM. A total of 1446 (55%) of heterosexual HIV positive adults were
      unaware of having had a high risk sexual contact. Late presentation among
      heterosexuals was associated with being male (aOR=1.58 95% CI 1.29-1.93), not
      knowing a partners' HIV status (OR=1.59 95% CI 1.35-1.87) and age, increasing the
      odds of late presentation by a factor of 1.02 per year (95% CI 1.01-1.03). Among
      MSM, only age was associated with late presentation, increasing by 1.04 (95% CI
      1.03-1.05) per year. CONCLUSIONS: Portuguese HIV prevention programs need to
      increase the risk awareness of heterosexuals, particularly men, to reduce missed
      opportunities for early diagnosis. As half of all cases presenting late are aged
      40 and over, we recommend that general HIV outreach services and specialist
      services for MSM review their accessibility and acceptability to both middle and
      older-aged clients.

PMID- 25397441
TI  - Characteristics of late presenters in Bucharest.
AB  - INTRODUCTION: Late presentation is associated with increased healthcare costs,
      rates of HIV transmission and poor outcome. In Romania, in 2012, one third of
      individuals with new HIV diagnosis were late presenters (LP). OBJECTIVE: The aim
      of the study was to evaluate the epidemiological and clinical characteristics
      associated with late presentation. METHODS: We retrospectively studied patients
      over 18 years old, notified in our institution between January 2012 and December
      2013, including 499 out of 727 newly diagnosed patients in Bucharest. LP were
      defined as patients presenting with CD4 T-cell count below 350 cells/mm(3) or
      with an AIDS defining event. Patients with advanced HIV disease (AHD) were
      defined as persons with a CD4 T-cell count below 200 cells/mm(3). Differences
      between groups were analyzed using the Mann-Whitney U test for continuous
      variables and the chi-square test for dichotomous variables. Multivariable
      analysis was performed using binary logistic regression. RESULTS: Out of 499
      patients included, 362 (72%) were male. The median age was 30 (IQR 26-36). A
      total of 302 (61%) were LP and 184 (37%) were patients with AHD. A total of 170
      (34%) were asymptomatic and 114 (23%) presented with an AIDS-defining event. The
      median CD4 count was 293 cells/mm(3) (IQR 125-471) and the median HIV viral load
      was 100,191 copies/mL (IQR 34,560-272,936). Characteristics of LP compared with
      non-LP are shown in Table 1. Stage C disease has been shown by multivariable
      analysis to be associated with LP (p<0.001, OR=11.56, 95% CI 4.94-27.03).
      CONCLUSIONS: More than half of newly HIV diagnosed patients in Bucharest were LP.
      The proportion of LP was highest among heterosexually acquired cases. Although
      most our patients were young, late presentation was associated with age over 35
      years. The lower proportion of LP among IVDU compared with those heterosexually
      infected could be explained by a higher proportion of HIV screening tests among
      IVDU.

PMID- 25397442
TI  - Late diagnosis among our ageing HIV population: a cohort study.
AB  - INTRODUCTION: With the advent of combined antiretroviral therapy (cART), more
      people infected with HIV are living into older age; 22% of adults receiving care
      in the UK are aged over 50 years [1]. Age influences HIV infection; the
      likelihood of seroconversion illness, mean CD4 count and time from infection to
      development of AIDs defining illnesses decreases with increasing age. A UK study
      estimates that half of HIV infections in persons over 50 years are acquired at an
      age over 50 [2]. Studies exploring sexual practices in older persons have
      repeatedly shown that we cannot assume there is no risk of STI and HIV infection
      [3,4]. Physicians should be alert to risk of HIV even in the older cohort, where
      nearly half diagnoses are made late [2]. Local audit has demonstrated poor
      testing rates in the over 50's on the Acute Medical Unit. Late diagnosis
      (CD4<350) results in poorer outcomes and age confounds further; older late
      presenters are 2.4 times more likely to die within the first year of diagnosis
      than younger counterparts [2]. MATERIALS AND METHODS: A retrospective case notes
      review was conducted of all patients aged 60 years and over attending HIV clinic
      in the last 2 years. Outcomes audited included features around diagnosis; age,
      presentation, missed testing opportunities and CD4 count at diagnosis. RESULTS:
      Of the current cohort of 442 patients, 34 were over 60 years old (8%). Age at
      diagnosis in this group ranged from 36 to 80 years, mean 56.6 years. Presentation
      triggers included opportunistic infections or malignancies (n=10), constitutional
      symptoms (n=6), diagnosis of another STI (n=4), seroconversion illness (n=2),
      partner status (n=3). Eight patients were diagnosed through asymptomatic
      screening at Sexual Health. We identified missed opportunities in five patients
      who were not tested despite diagnoses or symptoms defined as clinical indicators
      for HIV. Half of older patients had a CD4 count of <200 at diagnosis.
      CONCLUSIONS: It is imperative that general medical physicians and geriatricians
      are alert to enquiring about risk and testing for HIV where clinical indicators
      are present, irrespective of age. The oldest patient in the cohort was diagnosed
      with HIV aged 80 years. All patients with missed opportunities for testing were
      over 47 years old.

PMID- 25397443
TI  - Pregnancy outcomes in women growing up with perinatally acquired HIV in the
      United Kingdom and Ireland.
AB  - INTRODUCTION: In the United Kingdom and Ireland more than 40% of individuals
      living with perinatally acquired HIV are now aged >16. Globally, increasing
      numbers of women with perinatally acquired HIV are becoming pregnant, but data on
      fertility and pregnancy outcomes is scarce. We present pregnancy outcome data for
      this emerging cohort. METHODS: Pregnancies in diagnosed HIV-infected women in the
      United Kingdom and Ireland, and children diagnosed with HIV, are reported to the
      National Study of HIV in Pregnancy and Childhood. We analyzed data on pregnancies
      in women diagnosed aged <=13 with perinatally acquired HIV, reported by June
      2014. RESULTS: A total of 759 females born before 2001, diagnosed with
      perinatally acquired HIV aged <=13 years, and in care in the UK and Ireland have
      been reported. Forty-four of these (6%) have had at least one pregnancy reported,
      with nineteen 2nd and four 3rd/4th pregnancies. Women's year of birth ranged from
      1985 to 1996; 60% of women were UK/Irish-born and 39% African-born. Twenty one
      percent were diagnosed at <2 years, 39% at 2-7 and 41% at 8-13 years. Nine
      pregnancies were conceived in 2005-07, 22 in 2008-10 and 36 in 2011-13. Median
      age at conception of first pregnancy was 19 years. CD4 count was >500 cells/uL in
      36% of first pregnancies, 350-499 in 15% and <350 in 49%. Women were on
      antiretroviral therapy (ART) at conception in 71% of pregnancies. There were 51
      singleton live births, 2 miscarriages, 9 terminations and 5 continuing to term.
      In 17 live births to women not on ART at conception, median gestational age at
      start of ART was 17 weeks (range 3-29). HIV viral load was <50 copies/mL near
      delivery in 64% of live births, 51-1000 in 31% and >1000 in 5%. Forty four
      percent of live births were delivered by elective caesarean section (CS), 27% by
      emergency CS, 27% by planned vaginal delivery and with one unplanned vaginal
      delivery. Of 29 live births with viral load <50, 31% were delivered by elective
      CS, 17% by emergency CS and 52% by vaginal delivery. Fifteen percent of infants
      were delivered at 32-36 weeks gestation, and 2% at 30 weeks; 16% weighed 1.5-2.5
      kg and 16% weighed <1.5 kg. Among 38 of the 51 infants where infection status is
      already reported, one is perinatally infected. CONCLUSIONS: Currently at least 6%
      of perinatally infected women in care in the UK and Ireland have experienced one
      or more pregnancies. Linking paediatric, pregnancy and second generation data
      will enable further monitoring of pregnancy outcomes in this newly emerging
      population.

PMID- 25397444
TI  - The effect of tenofovir on renal function in HIV-positive pregnant women.
AB  - INTRODUCTION: Tenofovir is a commonly used component of antiretroviral therapy
      (ART) to reduce vertical transmission of HIV. Although systematic review of
      tenofovir use in pregnancy concluded it to be low risk for foetal abnormalities
      (1), data is limited on its impact on renal function in pregnant women. A recent
      South African study (2) concluded that renal dysfunction in HIV-infected pregnant
      women is significantly less common than in other HIV-infected adults, however
      there is currently no UK data. We aimed to investigate the effect of tenofovir on
      renal function in HIV-1 positive pregnant women in a UK clinic. METHODS: We
      retrospectively analyzed data on renal function in pregnancy from a cohort of
      women attending a busy inner city London antenatal clinic. All women were
      screened for renal function throughout pregnancy via serum creatinine and
      estimated glomerular filtration rate (eGFR) calculated using modification of diet
      in renal disease (MDRD) and corrected for ethnicity. RESULTS: Ninety-seven HIV-1
      positive women were registered at Homerton Hospital antenatal service of a total
      of 105 pregnancies between January 2010 and September 2013. Tenofovir was
      prescribed in 71/105 pregnancies (67.6%). Of the 71 pregnancies, 41 were
      prescribed tenofovir pre-conception (57.7%). Of the pregnant women who started
      tenofovir in pregnancy, 21/31 (67.7%) were initiated before week 24 of pregnancy,
      in line with British HIV association (BHIVA) guidelines (3). There was no
      deterioration in median serum creatinine or decline in eGFR in women prescribed
      tenofovir during pregnancy. At six weeks after delivery, in the 42 women who
      continued tenofovir therapy and had eGFR measured, one woman had eGFR=60, all
      others eGFR >90 (Table 1). CONCLUSIONS: Consistent with current guidelines and
      experience, this study shows tenofovir did not cause decline in renal function in
      pregnancy in our cohort of HIV-1 positive women, whether started during pre
      conception or during pregnancy. More evidence should be prospectively collected
      looking at effects of tenofovir on other measures of tubular renal function in
      pregnancy such as proteinuria and protein-creatinine ratio.

PMID- 25397445
TI  - The use of TDM in pregnant HIV-positive women: a retrospective cross-sectional
      review of five years practice in two large hospitals in Manchester.
AB  - INTRODUCTION: Despite plasma levels of certain HIV drugs decreasing in the third
      trimester of pregnancy there is no definitive evidence that therapeutic drug
      monitoring (TDM) improves HIV control and prevents mother-to-child transmission
      (MTCT). Indeed "one-off" TDM measurements are thought to poorly correlate with
      overall drug exposure [1]. We aim to describe baseline demographic and clinical
      characteristics of pregnant women with HIV, and to compare their HIV control,
      management during pregnancy and neonatal outcomes with respect to whether TDM was
      performed. MATERIALS AND METHODS: Retrospective cross-sectional case note
      analysis was performed on pregnant women with HIV who attended North Manchester
      General Hospital and Manchester Royal Infirmary from 1st January 2008 to 28th May
      2013. RESULTS: A total of 171 pregnancies were included; 39% (n=66) had TDM. The
      majority of patients were of African origin (85%) and age range was 16-42 years
      (median 32 years). TDM was found to be associated with a history of poor
      adherence to therapy (TDM 23%, vs no TDM 10%, p=0.017), although baseline viral
      load (VL) and CD4 counts were comparable between TDM and non-TDM groups (p=0.4756
      and 0.9492, respectively). TDM was also associated with protease inhibitors (PI)
      (TDM 94% vs no TDM 77%, p= 0.004). Within the PI group, TDM was more strongly
      associated with atazanavir use than other PI's (55%, p=0.023). TDM was not
      associated with any other demographic variable or with either of the two hospital
      sites (p=0.427). TDM was associated with medication alterations during pregnancy
      (TDM 67% vs no TDM 13%, p=0.052), but was not associated with any difference in
      outcomes with similar proportions of newly detectable VL during pregnancy (TDM
      12% vs no TDM 7%, p=0.220) and VL detectable at birth (TDM 14% vs no TDM 9%, p=
      0.293). There were no instances of MTCT. CONCLUSIONS: TDM was associated with PI
      use and a history of poor adherence at baseline. TDM was not associated with
      improved HIV control during pregnancy and there was no MTCT. TDM was not shown to
      have any additional benefit in pregnancy and its routine use is not recommended
      to improve HIV control or reduce MTCT.

PMID- 25397446
TI  - Morbidity and mortality in HIV-exposed under-five children in a rural Malawi
      setting: a cohort study.
AB  - INTRODUCTION: Paediatric HIV infection significantly contributes to child
      morbidity and mortality in southern Africa. In Malawi as in most countries in the
      region, care of HIV-exposed children is constrained by the lack of area-specific
      information on their risk to dying and morbidity. This research estimates and
      compares morbidity and mortality events between HIV-exposed and -unexposed under
      five children in a rural Malawian setting. METHODS: Data for children under the
      age of five collected from January 2009 to June 2011 at a demographic and health
      site in Karonga district of northern Malawi were analyzed. Morbidity and
      mortality rates among HIV-exposed and -unexposed children were calculated and
      compared using Kaplan-Meier survival analysis and Cox proportional hazard
      regression. RESULTS: Overall (n=7,929) cohort data of under-five children born in
      a demographic and health site represented 12380.8 person years of observation
      (PYO) of which 3.1% were contributed by HIV-exposed infants. Females accounted
      for half of the sample, and the overall mean age was 18.4 months (SD 13.4) with
      older children in the HIV-unexposed group. All-cause morbidity rate was
      337.6/1000 PYO (95% CI 327.5/1000-348.0/1000) and HIV-exposed children morbidity
      rate was 1.34 times higher (p<0.001) compared to HIV-unexposed children.
      integrated management of childhood illness (IMCI) pneumonia was the most common
      diagnosis (39.3%) in this cohort. Child mortality rate was 16.6/1000 PYO (95% CI
      14.5-19.1) from 206 deaths. HIV-exposed children had 4.5 times higher (p<0.001)
      mortality rate compared to the HIV-unexposed children. Higher mortality rates
      were observed in children under one year (129.2/1000 PYO) compared to older age
      groups. CONCLUSION: HIV exposure at birth has a greater impact on child morbidity
      and mortality especially in the first year of life. This underscores the need for
      targeted and synergetic interventions that included focused prevention of mother
      to-child transmission (PMTCT) which could reduce HIV transmission to children in
      their infancy in this setting.

PMID- 25397447
TI  - Severe birth defects in children perinatal exposed to HIV from a "real-world"
      setting: Infectious Diseases National Institute, Bucharest, Romania.
AB  - INTRODUCTION: The shift in epidemic trends in recent years in Romania shows new
      problems in regard of HIV vertical transmission, firstly in intravenous drug
      user's mothers co-infected with hepatitis viruses and with social problems, and
      secondly the children of young mothers with an old HIV infection and long
      antiretroviral therapy history. MATERIALS AND METHODS: We studied all HIV
      perinatal exposed children routinely followed up in the Paediatric Department of
      the National Institute of Infectious Diseases, since January 1st 2006 till
      December 31st 2012. The analyses consisted of describing the birth defects and
      association with certain risk factors: gender, mother's age at birth and exposure
      to antiretrovirals in the first trimester of pregnancy. RESULTS: We analyzed 244
      children born to HIV-infected mothers. The incidence of HIV infection was 16.39%.
      The rate of birth defects was 39.34% (96/244 cases). The most frequent findings
      were cardiac malformations (47/96), followed by musculoskeletal defects (24/96),
      neurologic defects (20/96), urogenital malformations (13/96), digestive tract
      defects (3/93), metabolic disorders (2/96) and genetic disorders (2/96). We found
      nine cases of severe congenital anomalies: complex heart defect, total congenital
      aganglionic megacolon, anal imperforation, Dandy-Walker syndrome, gangliosidosis,
      Niemann-Pick syndrome, Down syndrome, true hermaphroditism and cleft palate. Two
      children died during first year of life due to severe malformations. 9% of cases
      had associated malformations. The gender rate was in favour of males in group
      with birth defects (58/38) and with no birth defects (82/66). The median age at
      birth in mothers was 22 years, similar in both groups. The highest mean age at
      birth was in offspring's mothers with neurologic congenital defects 25, 15 years
      old, but is not statistically significant (p=0.1). In the studied period the
      highest number of birth defects were found in 2012, 37 children, compared with
      less than 15 in previous years (not statistically significant, p=0.07). In our
      studied patients the risk of birth defects was not statistically associated with
      HIV transmission or with exposure to antiretrovirals before and in first
      trimester of pregnancy (p=0.88). CONCLUSION: The rate of birth defects among HIV
      exposed children was not significantly associated with antiretroviral exposure,
      but we identify very rare and severe congenital conditions. We have noticed also
      a trend to increasing number of birth defects in 2012 among studied patients
      compared to previous years.

PMID- 25397448
TI  - ART management in children perinatally infected with HIV from mothers who
      experience behavioural changes in Romania.
AB  - INTRODUCTION: During the recent years the rate of HIV perinatally exposed
      children in Romania has increased as a consequence of the expanding number of HIV
      infected women. These women belong to Romania's long-terms survivors, aged
      between 20 and 24 years and to the group of new HIV infection cases (20-24
      years), acquired through unsafe sexual contact and use of new psychoactive
      substance (IV). MATERIALS AND METHODS: We focused on 396 HIV perinatally exposed
      children born between 2008 and 2013, under surveillance in National Institute for
      Infectious Diseases "Prof. Dr. Matei Bals," Bucharest. Of them, 43 acquired HIV
      through materno-foetal transmission. Our aim was to observe the characteristics
      in their evolution under antiretroviral treatment and to emphasize the causes of
      treatment failure. Children with perinatally acquired HIV infection were followed
      in a retrospective case series. We assessed maternal characteristics, HIV
      vertical transmission prophylaxis, timing of diagnosis, immunological and
      virologic status and features of the evolution under combined antiretroviral
      therapy (cART). RESULTS: The rate of mother-to-child HIV transmission was 10.8%
      versus the national rate registered in 2013, namely <5%. 16% of mothers belonged
      to the Romanian 1990s cohort and 84% were recently infected with HIV, through
      unprotected sexual contact (70%) or use of new psychoactive substances (14%). 51%
      of mothers were diagnosed postnatally as a consequence of their reluctance to
      access specific health services and in 57% CD4 value was <350 cell/mm. 41% of the
      monitored children were diagnosed with HIV infection at birth. Their median entry
      CD4 value was 23% and 49% had a CD4 >25%; median entry viral load was 7 log. 16
      patients (37%) had undetectable viral load after six months of treatment. In
      87.5% of them the virologic suppression was achieved and maintained with one
      single regimen (2 NRTIs+1 NNRTI or 2 NRTIs+1 PI/r). 15 children (35%) did not
      achieve suppression of viral load. 19 children (44%) faced special issues related
      to adherence to antiretroviral treatment, due to mothers' poor adherence to a
      basic set of cares destined for their children. CONCLUSIONS: Prevention
      programmes in Romania must be designed on the basis of the new economic context
      and emerging psychoactive substance use. Hence, women who use drugs should
      benefit from a wider access to medical and social services.

PMID- 25397449
TI  - Effectiveness of the prevention of mother-to-child transmission of HIV protocol
      applied at Saint Camille Medical Centre in Ouagadougou, Burkina Faso.
AB  - INTRODUCTION: Despite many prevention efforts, the number of children infected by
      HIV in sub-Saharan Africa through vertical transmission remains high. This
      infection can be reduced through programmes of prevention of mother-to-child HIV
      transmission (PMTCT). The objective of this study was to evaluate the
      effectiveness of the PMTCT protocol at Saint Camille Medical Centre in
      Ouagadougou, Burkina Faso. METHODS: From August 2012 to September 2013, samples
      of dried blood spot (DBS) were collected from 160 children aged 6 weeks born to
      HIV-1 positive mothers who were under PMTCT protocol at Saint Camille Medical
      Centre and 40 children of the same age group from orphanages and whose mothers
      were dead or unknown. The samples were tested using the Abbott Real Time HIV-1
      Qualitative kit. The clinical data of mothers were collected and analyzed using
      SPSS Version 17.0 and Epi Info Version 6.0 softwares. RESULTS: Among pregnant
      women in this study, 52.5% were predominantly young (24-29 years) and 60.62% were
      housewives. In total, 50.5% (101/200) were in combination of AZT/3TC/NVP and
      29.5% (59/200) were on prophylaxis (AZT/3TC). The rate of vertical transmission
      of HIV-1 was 0.0% (p<0.001) in children whose mothers were taking a combination
      of AZT/3TC/NVP (0/101) or were on a prophylaxis AZT/3TC treatment (0 /59). The
      rate of HIV-1 transmission in orphaned children was 15.0% (6/40). CONCLUSIONS:
      The PMTCT protocol is effective and reduces very significantly (p<0.001) the risk
      of transmission of HIV-1 from mother to child. In addition, screening by PCR of
      orphaned children vertically infected with HIV, enabled them to receive an early
      treatment.

PMID- 25397450
TI  - Possible association between the stage of HIV disease, antiretroviral treatment
      and the nutrient composition of breast milk in the Mangaung area, South Africa.
AB  - INTRODUCTION: In South Africa where replacement feeding may not be affordable,
      feasible or sustainable, HIV-infected women are recommended to exclusively
      breastfeed their infants during the first six months of life. The question arises
      whether HIV disease progression and its metabolic impact on the mother will
      affect the nutrient composition of breast milk. The aim was to determine the
      possible association between HIV disease progression, as measured by the
      immunological markers, and the nutrient composition of breast milk. METHODS: The
      nutrient composition of breast milk of 100 HIV-infected and 50 non-infected
      volunteered (control group) lodging/day visiting mothers at Paediatric/Neonatal
      wards of National, Pelonomi and Universitas hospitals, Bloemfontein, were
      measured. The HIV-infected group was subdivided into HIV-naive and HIV-ARV
      treatment group. Breast milk and blood samples were obtained. Macronutrients
      namely lactose, proteins, fat, total solids and the energy content of the breast
      milk and micronutrient namely calcium and phosphate were measured. Blood and
      immunological parameters comprised of CD4/CD8+T cell counts, viral loads and full
      blood counts. RESULTS: Protein levels amongst the HIV-infected group showed a
      significant elevation (p<0.0001) compared to the control group. The calcium
      levels of the HIV-infected group were significantly lower (p=0.0081) than the
      control group. No statistically significant differences were recorded of the
      measured nutrients between mothers receiving treatment and the HIV-naive group.
      All the HIV patients were anaemic with haemoglobin, haematocrit and RDW below the
      normal range. The Spearman Correlation Coefficient was used to determine if HIV
      disease progression have an influence on the nutrient composition. For the HIV
      naive group, a significant correlation was found between the viral load and
      percentage total solids in breast milk. A correlation between the CD4+T cell
      count, the percentage total solids and energy content of the breast milk was
      determined in the HIV-ARV treatment group. No strong positive correlation could
      be established between the immunological markers, HIV disease progression and the
      nutrient composition in the breast milk. CONCLUSIONS: HIV mothers can breastfeed
      their babies even at a more advanced stage of HIV disease progression, but
      emphasis has been placed on exclusive breastfeeding.

PMID- 25397451
TI  - The spectrum of HIV mother-to-child transmission risk.
AB  - INTRODUCTION: With the implementation of combined antiretroviral therapy (cART)
      and prevention of mother-to-child transmission (MTCT) we observed dramatic
      decreases in rates of perinatal MTCT of HIV, 0.3% in France in women with plasma
      viral load (pVL) <50 c/mL at delivery. We describe a case of MTCT which occurred
      despite virologic suppression of the mother at delivery, the first case in our
      centre since 2002. DESCRIPTION OF THE CASE: A 26-year-old black woman, Guinea
      native, living in France since 2007, was diagnosed with HIV-1 CRF02 in 2008 and
      lost to follow-up since November 2012 after second delivery (2 female born in
      March 2009 and October 2012, uninfected). Third pregnancy began in July 2013 and
      baseline characteristics in September were as follows: week 13 of gestational age
      (GA), CDC stage A, CD4 317/mm(3), pVL 4.89 log c/mL. cART with
      abacavir/lamivudine and atazanavir/ritonavir 300/100 mg daily (qd) was
      introduced. VL decreased to 2.4 log c/mL in 4 weeks and CD4 increased to
      456/mm(3). In December, at week 22 of GA, viral rebound at 4.14 log c/mL due to
      sub-optimal maternal adherence was observed. After counselling, pVL decreased to
      1.69 log c/mL in March 2014, at week 35 of GA and 1.3 log c/mL at delivery. As
      pVL was <400 c/mL at week 36 of GA, vaginal delivery with IV zidovudine was
      decided. However, because of poor/uncertain maternal adherence to cART, the
      neonate was treated with a combination of 2 drugs (lamivudine-nevirapine) with
      the 4-week zidovudine regimen, until the result of delivery pVL. This combination
      was stopped at day 2 when maternal delivery pVL (22 c/mL) was received and
      standard oral zidovudine prophylaxis was continued. Infant was tested for HIV
      infection at baseline (day 3) and found to be HIV-infected (HIV-RNA 60 c/mL)
      attesting in-utero HIV transmission. On day 15, zidovudine prophylaxis was
      discontinued and treatment for HIV infection initiated with standard cART
      according to the French Paediatric Antiretroviral Guidelines. CONCLUSIONS: The
      risk of HIV acquisition is low in infants born to women who receive standard cART
      during pregnancy and labour and achieve undetectable VL at delivery. However,
      transmission remains a hazard, with possibility of in-utero infection during
      episodes of non-adherence, and the risk of a possible MTCT has to be mentioned to
      all pregnant women.

PMID- 25397452
TI  - Transmitted drug resistance in women with intrapartum HIV-1 diagnosis: a pilot
      epidemiological survey in Buenos Aires, Argentina.
AB  - INTRODUCTION: Surveillance of primary resistance to antiretroviral drugs is
      particularly important in pregnant population, in which infection by drug
      resistant HIV has not only implications for maternal treatment, but could also
      jeopardize the efficacy of neonatal prophylaxis. We aim to describe the
      prevalence of resistance associated mutations (RAMs) in pregnant women with
      intrapartum HIV diagnosis in a public hospital of Buenos Aires, Argentina.
      MATERIALS AND METHODS: Prospective pilot study (period from 2008 to October
      2013). Plasma samples were tested for viral load by Versant HIV-1 RNA 3.0 (bDNA)
      and sequenced using HIV-1 TRUGENETMGenotyping Kit (Siemens). The prevalence of
      RAMs was analyzed according to World Health Organization (WHO) criteria. RESULTS:
      Of 231 HIV-infected pregnant women assisted, 6% (n=14) had intrapartum diagnosis
      of HIV infection. 12 patients (85.7%) had previous pregnancies, 10 (71.4%) had
      inadequate prenatal care and 3 (23.1%) seroconverted during pregnancy. Maternal
      characteristics (expressed medians and ranges) were: age 25.5 (16-35) years;
      gestational age at birth: 39 (30-42) weeks; CD4 count: 500 (132-925) cells/uL;
      viral load: 9418 (1800-55299) copies/mL. No one had hepatitis B virus (HBV) or
      hepatitis C virus (HCV) coinfection; four (33.3%) had syphilis. Eight patients
      (57.1%) had vaginal delivery and six emergency C-section (42.9%). In six cases
      (46.2%), membrane rupture was spontaneous; four patients (28.6%) failed to
      receive intrapartum zidovudine (ZDV) infusion. In 12 patients a genotypic
      resistance test was performed: two (16.7%) had WHO RAMs corresponding to K103N
      mutation in both cases, conferring high-level resistance to nevirapine (NVP) and
      efavirenz. Two newborns (14.3%) were preterm. All received neonatal prophylaxis:
      ZDV in 1 case and combined prophylaxis (ZDV/3TC/NVP) in the remaining 13 (92.9%).
      All newborns were formula-fed. Two (14.3%) had congenital syphilis, one of whom
      died. One newborn was HIV-infected (positive proviral DNA at 24 hours of life,
      wild-type HIV). CONCLUSIONS: This pilot study suggests that levels of transmitted
      resistance in this high-risk population of pregnant women could be moderate to
      high. We preliminarily observed high-level resistance to NVP: if this finding is
      confirmed with a larger sample, it could potentially jeopardize the utility of
      this drug in the combined neonatal prophylaxis recommended in the absence of
      maternal antiretroviral therapy.

PMID- 25397453
TI  - Prevention of mother-to-child transmission: experience of a Portuguese centre.
AB  - INTRODUCTION: HIV infection during pregnancy still raises controversial issues.
      Combined antiretroviral therapy (cART) has been successful in reducing mother-to
      child transmission (MTCT). Routine screening in pregnancy and in pre-conception
      consultation proved to be one of the best methods able to get this treatment on
      time. We review our experience with pregnant patients with HIV infection.
      MATERIALS AND METHODS: Retrospective and descriptive study. Data obtained from
      HIV-infected pregnant women from 1999 to 2012 with delivery and subsequent
      infectious diseases follow-up at our hospital. RESULTS: We evaluated 136 patients
      (169 pregnancies), with a total of 147 living newborns (2 twin pregnancies) and 1
      stillbirth. Median age at pregnancy was 30 (SD 5.7) years. Four patients were HIV
      2 infected and one HIV-1+2 infected. 26 (19.1%) women were HCV co-infected and 6
      (4.4%) HBV co-infected; 1 patient has HCV and HBV co-infection. Sexual risk for
      HIV acquisition was determined in 102 (75%) patients and 31 (22.8%) were
      intravenous drug users. 33/136 (24.2%) women were diagnosed on routine screening
      in pregnancy, 4 during delivery and 2 immediately after delivery. 36 (26.4%)
      patients had an AIDS-defining entity before pregnancy and no new opportunistic
      infections were diagnosed. ART was used in 157 (92.9%) pregnancies and 15 (9.5%)
      of them were treated only with NRTIs. At the time of delivery 86/144 (59.7%)
      patients had undetectable viral load (VL) (25 patients without VL determined),
      91.7% of those on ART. 119 (70.4%) had a TCD4 cell count above 200 cells/mm(3).
      MTCT occurred in 3/147 cases (2%): in one mother HIV-1 infection was diagnosed
      three weeks before delivery, other immediately after delivery and the third woman
      started cART (2NRTI+1PI/r) in the second trimester of pregnancy, always adherent
      and without secondary effects, VL at delivery was 50 copies/mL and elective C
      section was performed. CONCLUSIONS: The fact that 24% of patients were diagnosed
      during pregnancy shows the importance of routine screening to all pregnant women.
      MTCT occurred in three children, but only one was administered cART for
      prevention.

PMID- 25397454
TI  - Universal Tre (uTre) recombinase specifically targets the majority of HIV-1
      isolates.
AB  - Current drugs against HIV can suppress the progression to AIDS but cannot clear
      the patient from the virus. Because of potential side effects of these drugs and
      the possible development of drug resistance, finding a cure for HIV infection
      remains a high priority of HIV/AIDS research. We recently generated a recombinase
      (termed Tre) tailored to efficiently eradicate the provirus from the host genome
      of HIV-1 infected cells by specifically targeting a sequence that is present in
      the long terminal repeats (LTRs) of the viral DNA [1]. In vivo analyses in HIV
      infected humanized mice demonstrated highly significant antiviral effects of Tre
      recombinase [2]. However, the fact that Tre recognizes a particular HIV-1 subtype
      A strain may limit its broad therapeutic application. To advance our Tre-based
      strategy towards a universally efficient cure, we have engineered a new,
      universal recombinase (uTre) applicable to the majority of HIV-1 infections by
      the various virus strains and subtypes. We employed the search tool SeLOX [3] in
      order to find a well-conserved HIV-1 proviral sequence that could serve as target
      site for a universal Tre from sequences compiled in the Los Alamos HIV Sequence
      Database. We selected a candidate (termed loxLTRu) with a mean conservation rate
      of 94% throughout the major HIV-1 subtype groups A, B and C. We applied loxLTRu
      as substrate in our established substrate-linked protein evolution (SLiPE)
      process [4] and evolved the uTre recombinase in 142 evolution cycles. Highly
      specific enzymatic activity on loxLTRu is demonstrated for uTre in both
      Escherichia coli and human cells. Naturally occurring viral variants with single
      mutations within the loxLTRu sequence are also shown to be efficiently targeted
      by uTre, further increasing the range of applicability of the recombinase.
      Potential off-target sites in the human genome are not recombined by uTre.
      Furthermore, uTre expression in primary human T cells shows no obvious Tre
      related cytopathic or genotoxic effects. Finally, uTre expressing mice show no
      undesired phenotypes during their normal lifespan. We have developed a broad
      range HIV-1 LTR specific recombinase that has the potential to be effective
      against the vast majority of HIV-1 strains and to cure HIV-1 infected cells from
      the infection. These results strongly encouraged us in our confidence that a Tre
      recombinase-mediated HIV eradication strategy may become a valuable component of
      a future therapy for HIV-infected patients. 

PMID- 25397455
TI  - Targeted destruction of HIV-positive cells.
AB  - INTRODUCTION: HIV/AIDS is now a global epidemic that has become the leading
      infectious killer of adults worldwide. Although antiretroviral (ARV) therapy has
      dramatically improved the quality of life and increased the life expectancy of
      those infected with HIV but frequency of dosing and drug toxicity as well as the
      development of viral resistance pose additional limitations. The rapidly
      expanding field of nanotechnology has vast potential to radically advance the
      treatment and prevention of HIV/AIDS. Nanoparticles can provide improved drug
      delivery, by virtue of their small size, robustness, safety, multimodality or
      multifunctionality. AIMS AND OBJECTIVES: Since HIV primarily infects CD4+ cells;
      we aim to use CD4 as a selectable target to deliver a pro-apoptotic protein to
      HIV-infected cells using nanoparticles as carriers. The aim of study was to
      develop a nanotechnology-based death inducing delivery system for the destruction
      of CD4+HIV infected cells through the activation of caspase-3. METHODOLOGY: A
      modified caspase-3 protein (Mut-3) was engineered, which is cleavable only by HIV
      1 protease. Mut-3 can activate apoptosis in the presence of HIV-1 protease,
      consequently killing HIV-positive cells. Mut-3 protein was conjugated to gold
      nanoparticles together with a CD4-targeting peptide. The efficacy of the gold
      nanoparticles was tested on CHO cells that were genetically engineered to express
      GFP labelled CD4 and HIV-1 protease. RESULTS: Mut-3 was expressed in bacterial
      cells and purified. CHO cells that stably over express CD4-GFP and HIV-1 protease
      were selected using Fluorescence Activated Cell Sorting. Dose response cell
      culture experiments showed that gold nanoparticles without Mut-3 and CD4
      targeting peptide did not induce cell death in CHO cells, while gold
      nanoparticles that was conjugated with Mut-3 and the CD4-targeting peptide
      rapidly induced cell death in CHO cells. CONCLUSIONS: Our results suggest that
      gold nanoparticles conjugated with Mut-3 and a CD4-targeting peptide could
      potentially induce apoptosis in HIV-infected cells.

PMID- 25397456
TI  - CD4/CD8 ratio is not predictive of multi-morbidity prevalence in HIV-infected
      patients but identify patients with higher CVD risk.
AB  - BACKGROUND: CD4/CD8<0.8 is a surrogate marker of immune
      activation/immunosenescence and independently predicts mortality in the HIV
      infected patients due to non-AIDS related events. Most studies showed that
      patients on antiretroviral therapy (ART) often fail to normalize the CD4/CD8
      ratio despite CD4 count normalization. Primary objective of the study was to
      explore the impact of CD4/CD8<0.8 as independent predictor of HIV-associated non
      AIDS (HANA) conditions and multimorbidity (MM) in HIV patients. In patients with
      no previous history of cardiovascular disease (CVD) a particular insight is
      provided in the association between impact of CD4/CD8<0.8 and risk prediction of
      CVD or radiological markers of subclinical CVD. MATERIALS AND METHODS: 914
      consecutive patients attending Modena Metabolic HIV Clinic were evaluated in a
      cross-sectional retrospective study. INCLUSION CRITERIA: stable ART from >=2
      years; HIV-RNA plasma levels<40 copies/mL; stable CD4 count>=350/mmc. CD4/CD8
      strata (0.8) was chosen as a cut off representing the median value of the cohort.
      MM was defined as the presence of>=2 HANA conditions including standard defined:
      chronic kidney disease, hypertension, previous CVD events, osteoporosis and
      diabetes mellitus. Calendar year of ART initiation was defined: "PreART" (<2000);
      "EarlyART" (2000-2005) and "LateART" (>=2006). High CVD risk was defined for
      Framingham Risk Score (FRS)>=6. Subclinical CVD was defined using cardiac CT scan
      for calcium score (CAC)>=100. Logistic univariate and multivariable adjusted
      analysis were performed to assess relationships between variables. RESULTS:
      Demographic and HIV-specific variables distribution in patients with and without
      MM are shown in Table 1. CONCLUSIONS: Low CD4/CD8 ratio was not associated with
      MM prevalence. Patients with CD4/CD8<0.8 ratio displayed higher prevalence of
      CVD. At multivariable logistic regression CD4/CD8<0.8 is an independent
      prepredictor of enhanced CVD risk. This may support role of immune
      activation/senescence in the pathogenesis of CVD.

PMID- 25397457
TI  - Viro-immunological characterization of naive patients with high cerebrospinal
      fluid (CSF) HIV RNA.
AB  - BACKGROUND: HIV can spread into the central nervous system (CNS) early in the
      course of infection and this turns into intrathecal inflammation and neuronal
      damage. We aimed to investigate clinical and immunological parameters associated
      with elevated CSF VL in HIV-infected ART-naive patients. MATERIALS AND METHODS:
      HIV+ ART-naive patients underwent a comprehensive battery of neurocognitive (NC)
      tests and lumbar puncture (LP) for CSF HIV-RNA detection. Plasma HIV-RNA and
      peripheral T-cell immune-phenotypes (CD38/CD45RA/CD45R0/CD127 on CD4/CD8) were
      also assessed (flow cytometry). High-CSF HIV RNA was defined as>=10000cp/mL (H
      CSF), while CSF HIV RNA<10000cp/mL characterized low VL patients (L-CSF). Chi
      square and Mann-Whitney tests were used. Parameters independently associated with
      CSF VL were explored by multivariate regression. RESULTS: A total of 131 patients
      were retrospectively enrolled. Forty-two patients (32%) had CSF VL >10000 cp/mL.
      CONCLUSIONS: We hereby describe a 32% prevalence of H-CSF in a cohort of HIV+ ART
      naive patients. Subjects with high-CSF viral replication are mostly with higher
      systemic immune activation, in particular the percentage of naive CD8 T-cell is
      positively associated with CSF VL, irrespective of plasma VL. In HIV+ ART-naive
      patients, especially if featuring a hyperactivated T-cell immune-phenotype,
      lumbar puncture should be considered to further guide CNS-targeted cART.

PMID- 25397458
TI  - Overall and cause-specific mortality in HIV-positive subjects compared to the
      general population.
AB  - INTRODUCTION: Emerging non-AIDS related causes of death have been observed in HIV
      positive subjects in industrialized countries. We aimed to analyze overall and
      cause-specific excess of mortality of HIV-positive patients compared to the
      general population and to assess the effect of prognostic factors. MATERIAL AND
      METHODS: We used generalized linear models with Poisson error structure to
      estimate overall and cause-specific excess of mortality in HIV-positive patients
      from 2004 to 2012 in the cohort of the Spanish Network of HIV Research (CoRIS),
      compared to Spanish general population and to assess the impact of multiple risk
      factors. We investigated differences between short-term and long-term risk
      factors effects on excess of mortality. Multiple Imputation by Chained Equations
      was used to deal with missing data. RESULTS: In 9162 patients there were 363
      deaths, 16.0% were non-AIDS malignancies, 10.5% liver and 0.3% cardiovascular
      related. Excess mortality was 1.20 deaths per 100 person years (py) for all-cause
      mortality, 0.16 for liver, 0.10 for non-AIDS malignancies and 0.03 for
      cardiovascular. Short-term (first-year follow-up) excess Hazard Ratio (eHR) for
      global mortality for baseline AIDS was 4.27 (95% CI 3.06-6.01) and 1.47 (95% CI
      0.95-2.27) for HCV coinfection; long-term (subsequent follow-up) eHR for baseline
      AIDS was 0.88 (95% CI 0.58-1.35) and 4.48 (95% CI 2.71-7.42) for HCV coinfection.
      Lower CD4 count and higher viral load at entry, lower education, being male and
      over 50 years were predictors for overall excess mortality. Excess of liver
      mortality was higher in patients with CD4 counts at entry below 200 cells
      compared to those above 350 (eHR: 6.49, 95% CI 1.21-34.84) and in HCV-coinfected
      patients (eHR: 3.85, 95% CI 0.85- 17.37), although it was borderline significant.
      Patients over 50 years old (eHR: 5.55, 95%CI 2.4-12.85) and HCV coinfected (eHR:
      5.81, 95% CI 2.6-13) showed a higher risk of non-AIDS malignancies mortality
      excess. Excess of cardiovascular mortality was related with HCV coinfection (eHR:
      6.68, 95% CI 1.25-35.73). CONCLUSIONS: Our results show overall, liver, non-AIDS
      malignancies and cardiovascular excess of mortality associated with being HIV
      positive, despite improvements in HIV disease management and antiretroviral
      therapies. Differential short-term and long-term effect of AIDS before entry and
      HCV coinfection was found for overall mortality.

PMID- 25397459
TI  - A comparison of inpatient admissions in 2012 from two European countries.
AB  - INTRODUCTION: This study compares the trends of HIV inpatient admissions between
      a London tertiary HIV centre (United Kingdom) and four infectious disease wards
      in Italy (IT) to recognize common patterns across Europe. METHODS: Data regarding
      HIV inpatient admissions was collected by using discharge diagnostic codes from 1
      January to 31 December 2012, including patient demographics, combined
      antiretroviral therapy (cART) history, CD4, viral load (VL) and mortality rates.
      Discharge diagnoses were categorized according to the International
      Classification of Disease (ICD) 9 and 10 system. All ICD categories that reach a
      3% threshold of total admissions were analyzed. RESULTS: A total of 731
      admissions (257 in Italy and 474 in the United Kingdom) for 521 patients (1.5
      mean admission per patient). Female admissions were higher in Italy at 22.6%
      (n=58) compared to 14.9% (n=47) in the United Kingdom. Median age of patients was
      47 years old. There was an undetectable VL in 65.8% (n=169) of admissions in
      Italy and 67.1% (n=319) in the United Kingdom (p=0.385); 86.4% (n=222) and 82.4%
      (n=389) of admissions were on cART, respectively. Mean CD4 was 302 in Italy
      compared to 368 in the United Kingdom (p=0.003). Average length of admission was
      16 days with a 10.2% (n=21) mortality rate in Italy compared to 8 days with 2.8%
      (n=9) mortality in the United Kingdom (p<0.001). HCV co-infection was present in
      64.6% (n=166) in Italy and 13.5% (n=64) in the United Kingdom and commonest mode
      of transmission was needle use in Italy (67.3%, n=173) and men who have sex with
      men in the UK cohort (59.9%, n=284). The cause of inpatient admissions according
      to ICD codes can be seen in following Figure 1. CONCLUSIONS: Significant
      differences in the duration of inpatient admission and mortality rates can be
      observed between these two cohorts which is secondary to the impact of Hepatitis
      C co-infection in Italy. However increases in the number of Hepatitis C co
      infection patients amongst MSM in London has been reported [1] and route of
      transmission in Italy is shifting towards MSM [2], therefore it is important to
      learn how HIV is developing and managed in a global context to help plan future
      for services. The UK cohort demonstrates a wider range of conditions
      necessitating admission, and with an ageing HIV population, this is expected to
      increase in the future, requiring general and specialist HIV physicians to work
      closely together. The HIV-RNA threshold is 400 copies/mL to account for blips
      according to British HIV Association (BHIVA) Guidelines 2012 [3].

PMID- 25397460
TI  - The potential impact of new national guidance on primary prevention of
      cardiovascular disease in people living with HIV.
AB  - INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in
      England and Wales. As people living with HIV (PLWH) age, proactive management of
      CVD risk factors is crucial. The long-awaited draft guidelines for CVD from the
      National Institute of Clinical Excellence (NICE) propose lipid modification (with
      statins) and lifestyle modification for 40-74 year olds with >10% (previously
      >20%) 10-year risk of CVD using QRISK2. We currently use Framingham so compared 3
      CVD risk calculators in our cohort and analyzed the impact of a change in CVD
      threshold on the proportion of our patients who would need intervention.
      MATERIALS AND METHODS: Framingham, QRISK2 and JBS3 cardiovascular risk
      calculators were compared in a group of randomly selected patients. Then, to
      analyze the impact of a change in primary prevention threshold on our cohort, we
      interrogated a prospectively collected database to identify all individuals who
      had a documented Framingham risk assessment and applied the current/proposed
      thresholds accordingly. We performed the same analysis for the three calculator
      subgroup (recalculating Framingham risk). Finally we surveyed HIV services in
      England & Wales regarding their choice of calculator. RESULTS: We compared the 3
      CVD risk calculators in 100 patients, see Table 1. CONCLUSIONS: Reducing the
      threshold for cardiovascular preventative measures to 10% vastly increases the
      number of patients requiring primary intervention, from two- to fourfold
      depending on risk calculator used. This may have significant implications,
      including cost, drug-drug interactions and patient experience, that HIV
      physicians and general practitioners will need to address, ideally in a
      coordinated and patient-focused manner.

PMID- 25397461
TI  - Association between abdominal aortic calcifications, bone mineral density and
      vertebral fractures in a cohort of HIV-positive patients.
AB  - INTRODUCTION: Evidence from HIV-negative cohorts suggests a link between
      osteoporosis and cardiovascular disease. We evaluated the presence and
      distribution of abdominal aortic calcifications (AAC) and its correlation with
      bone mineral density (BMD) and vertebral fractures (VF) in a cohort of HIV
      positive patients. MATERIALS AND METHODS: In this cross-sectional study, 280
      asymptomatic HIV-positive patients from the SPID ("San Paolo" Infectious
      Diseases) cohort were submitted to lateral spine X-ray and DXA. AAC was
      identified using the AAC-8 score, which estimates the total length of
      calcification of the anterior and posterior aortic walls in front of vertebrae L1
      L4. Low BMD was defined by T-score or Z-score <-1 at lumbar spine or femoral
      neck. VF were identified by morph-metric analysis of X-ray and were defined by
      the "spine deformity index" (SDI) >=1 according to semiquantitative method by
      Genant. Associations between AAC, BMD and SDI were evaluated by univariate and
      multivariate logistic regression models. The relationship between the grade of
      AAC and SDI was evaluated by Spearman's correlation. RESULTS: AAC>=1 was present
      in 65 patients (23.2%); of these 15 patients showed moderate/severe
      calcifications (AAC>2). Low BMD was found in 163 patients (58.2%) and VF (SDI>=1)
      in 47/274 patients (17.1%). By univariate analysis, factors associated with
      AAC>=1 were: age (for additional 10 years older HR 3.81 [IC95% 2.64-5.51],
      p<0.0001) lower CD4 nadir (for additional 50 CD4 HR 0.89 [IC95% 0.82-0.97],
      p=0.01) AIDS-diagnosis (HR 2.13 [IC95 % 1.11-4.08], p=0.02) and being on HAART
      (HR 2.75 [IC95% 1.28-5.90], p=0.009). In multivariate analysis, only age (OR
      2.62, IC95% 1.72-3.99, p<0.0001) resulted significantly associated with AAC>=1.
      Patients with AAC>=1 had twofold increase in the risk of low BMD (HR 2.45 [IC95%
      1.32-4.45], p=0.004) and VF (SDI>=1: HR 2.17 [IC95% 1.1-4.2], p=0.02) compared to
      patients without AAC. The grade of AAC was directly correlated with the grade of
      SDI (rho=0.16; p=0.008): AAC>2 determines a sixfold increase in the risk of VF
      (HR 6.44 [IC95% 2.21-18.79], p=0.0006). AAC>=1 predict VF independently from BMD,
      vitamin D status and bone turnover marker (Table 1). CONCLUSIONS: In our HIV
      population, AAC resulted a strong predictor of both low BMD and VF, irrespective
      of factors involved in bone formation. The grade of AAC was directly correlated
      with the grade of VF.

PMID- 25397462
TI  - Burden of subclinical heart and lung disease detected on thoracic CT scans of HIV
      patients on HAART.
AB  - INTRODUCTION: The aim was to determine the prevalence of lung and heart
      abnormalities on thoracic CT scans in HIV-infected patients who were treated with
      antiretroviral therapy (ART). MATERIAL AND METHODS: Thoracic CT scans of 903
      patients infected with HIV (mean age 48+/-7 yrs, 29% females) were reviewed by
      three radiologists by consensus. Patients were phenotyped according to smoking
      status, pack years and years since cessation for ex-smokers. Individuals known to
      have active lung or heart disease at the time of CT scanning were excluded.
      Multimorbidity lung and heart disease (MLHD) was defined by the presence of >2
      lung or heart abnormalities on the CT scan. RESULTS: Prevalence of lung
      abnormalities were: 326 patients (36.1%) with emphysema, 271 (30.0%) with
      bronchiolitis, 44 (4.9%) with non-calcified lung nodules, 568 (63%) with
      significant bronchial wall thickening, 150 (16.7%) with bronchiectasis, 9 (1%)
      with interstitial lung disease. Overall, 445 patients (49.3%) had >2 lung
      abnormalities. Imaging findings suggestive of prior myocardial infarction (MI)
      were found in 1.4% (13 patients); 26.6% (240 patients) had CAC scores of 1 to
      100, and 9.8% (89 patients) had CAC>100. 13.6% (123 patients) of the patients had
      CAC>100 and/or previous MI. MLHD was present in 484 patients (53.6%) and among 78
      patients (16%) who never smoked. Table 1 describes CT findings according to pack
      year and stop smoking groups vs never smokers. CONCLUSIONS: MLHD is common in HIV
      infected individuals even in non-smokers. Reduced CD4 count (hence severity of
      HIV infection) may be an important risk factor for chronic lung and heart
      disease. Thoracic CT scans may provide an excellent screening tool to detect MLHD
      in HIV-infected patients.

PMID- 25397463
TI  - Factors associated with HPV-DNA clearance in a cohort of HIV-positive patients:
      role of cART and gender.
AB  - INTRODUCTION: We aimed to assess any factors associated with dysplasia regression
      and with HPV clearance in a cohort of HIV+ patients, with particular focus on
      cART and gender. METHODS: Asymptomatic HIV+ patients of the San Paolo Infectious
      Disease (SPID) cohort who underwent anoscopy/gynaecological evaluation were
      enrolled. Anal/cervical brushing were analyzed for: HPV-PCR detection/genotyping
      (HR-HPV), cytologic abnormalities (Bethesda System 2001: LSIL-HSIL). Demographics
      and HIV-related parameters were evaluated at baseline. Activated CD8+/CD38+
      lymphocytes were measured (flow citometry). Patients were examined at baseline
      (T0) and at 12-18 months visit (T1). HPV clearance was defined as negativisation
      of HPV at T1; SIL regression (SIL-R) and progression (SIL-P) were defined as
      change from HSIL/LSIL to a lower-grade/absence of dysplasia and as change from
      absence of HSIL/LSIL to a higher-grade dysplasia at T1, respectively. Mann
      Whitney test, Chi-square test and multivariate logistic regression were used.
      RESULTS: A total of 189 patients were examined, 60 (32%) were women. One hundred
      fifty patients (79%) were HPV+, 113 (75%) harboured HR-HPV; 103 (68%) showed
      LSIL/HSIL at T0 (32% of women and 65% of men) (all were HPV-positive). No
      differences in demographics and HIV-related markers were found between patients
      with SIL-P (33, 41%) and patients with SIL-R (47, 59%). HPV+ patients who cleared
      HPV (28, 18%) were found to be more frequently female, heterosexual infected,
      more frequently on cART and with lower Log10 HIV-RNA and lower levels of
      CD8+/CD38+ % compared with HPV persistence group (Table 1). CONCLUSIONS: Close
      follow-up of HPV and SIL should be promoted particularly in men and in untreated
      individuals. We cannot exclude behavioural variables linked to risky sex and
      reinfection.

PMID- 25397464
TI  - Relationship between innate immunity, soluble markers and metabolic-clinical
      parameters in HIV+ patients ART treated with HIV-RNA<50 cp/mL.
AB  - INTRODUCTION: The persistence of immune activation and inflammation in HIV
      patients with HIV-RNA (VL) undetectable causes many co-morbidities [1-3]. The aim
      of this study is to correlate monocytes (m) and NK cell activation levels,
      soluble markers and oxidative stress with clinical, biochemical and metabolic
      data in HIV-1 infected patients with VL<=50 copies (cp)/mL on antiretroviral
      therapy. MATERIALS AND METHODS: Multicentre, cross-sectional study in patients
      with VL<=50 cp/mL and on antiretroviral therapy by at least six months. We
      studied: activation/homing markers (CD38, HLA-DR, CCR-2, PDL-1) on inflammatory,
      intermediate, proinflammatory m; activatory receptors NKp30, NKp46 and HLA-DR on
      NK cells; soluble inflammatory (sCD14, adiponectina, MCP-1) and stress oxidative
      markers (dRoms, antiRoms). Univariate analyses are performed with non-parametric
      and Pearson tests. The significant correlations were adjusted for possible known
      confounding factors (smoking, Cytomegalovirus IgG serology, Raltegravir, Protease
      Inhibitor [PI] therapy and HCV-RNA) with multivariate analysis. RESULTS: In the
      68 patients the positive correlation between age and antiRoms was significant
      also after adjustment for PI use (p=0.05). The% CD8+T was associated with%
      proinflammatory m (p=0.043) and with their expression of CCR2 mean fluorescence
      intensity (MFI) (p=0.012). The% NKp46+ was positively correlated with CD4+T count
      (p=0.001). The fibrinogen was positively associated with dRoms (p=0.052) and the
      positive correlation between triglycerides and antiRoms has been confirmed
      (p<0.001); the impact of antiRoms on HDL/triglycerides ratio (p=0.006) was
      observed after adjustment for PI use. The BMI was associated with smoking
      (p=0.011). Only the maraviroc-treated patients showed minimal arterial pressure,
      fibrinogen and antiRoms lower (p=0.001, 0.004 e 0.006) and sCD14 values higher
      (p=0.029). CONCLUSIONS: Patients with long history of HIV infection and stable
      immunological and virological status showed interactions between acquired and
      innate immunity activation; moreover, the levels of some metabolic and
      inflammatory parameters correlate with oxidative stress values and innate
      immunity activation. The age, BMI and smoking impact metabolic and immunological
      parameters. The correlations between antiretroviral drugs and clinical
      immunological parameters need further confirmations.

PMID- 25397465
TI  - Cerebrospinal fluid biomarkers in patients with plasma HIV RNA below 20
      copies/mL.
AB  - INTRODUCTION: Low level HIV-1 CSF replication (CsfLLV) is often found even in
      patients with controlled plasma viraemia. The clinical consequences of such
      finding are uncertain; however, both symptomatic neurological disturbances and
      neurocognitive disorders may arise in the context of CSF-escape. Two reports
      suggested that low level replication in the CSF may be associated with increased
      CSF neopterine although the impact on other markers of neuroinflammation/damage
      is currently unknown. MATERIALS AND METHODS: Patients with neurocognitive
      disorders, new neurological symptoms or followed in longitudinal studies were
      included provided that they were on HAART, with last available viral load below
      20 copies/mL and without central nervous system (CNS)-involving
      infections/neoplasms. After brain Magnetic Resonance (MR) CSF HIV RNA (CAP/CTM
      HIV-1 v2.0) and biomarkers [total tau (t-tau), phosphorylated tau (p-tau), 1-42
      Beta amyloid (Beta42), neopterine and S100beta] were measured through validated
      methods. Data are presented as medians (IQR); non-parametric tests are used for
      all analysis. RESULTS: 70 patients [66.7% male, median age 47.8 years (40-56),
      median BMI 22.2 kg/m2 (20-24)] were enrolled. Current and nadir CD4+ cell count
      were 379 (219-656) and 116 cell/mm3 (46-225); HIV RNA was undetectable since 19.7
      months (9-53). CSF HIV RNA was undetectable in 24 (34.3%), below 20 copies/mL in
      26 (37.1%), above 20 copies/mL in 25 patients [35.7%, median 69 copies/mL (41
      134]). Median (IQR) CSF biomarkers values were as follows: t-tau 109 pg/mL (<75
      161), p-tau 31.6 pg/mL (23.4-35.4), Beta42 818 pg/mL (623-973), neopterine 0.58
      ng/mL (0.45-0.87) and S100beta 149 pg/mL (110-186). Patients with CsfLLV did not
      show significant differences as for demographic, therapeutic, virological,
      radiological variables. t-tau (134 vs 92.6, p=0.05) and Beta42 (953 vs 675,
      p=0.007) were higher in patients with CsfLLV. Neopterine levels were directly
      associated with p-tau (rho=0.42, p=0.01), with CSF HIV RNA (rho=0.24, p=0.06).
      and inversely with current CD4 cell count (rho=-0.29, p=03). CONCLUSIONS: In
      patients with controlled HIV viraemia (below 20 copies/mL), CSF total tau, Beta42
      and neopterine were higher in patients with detectable HIV RNA. Prospective and
      adequately powered studies are warranted for evaluating the clinical significance
      of compartmental viral replication and immune activation.

PMID- 25397466
TI  - Depression in HIV-positive women is associated with changes in antiretroviral
      treatment regimens.
AB  - INTRODUCTION: Depression is a co-morbidity of clinical significance in HIV
      positive patients with an estimated prevalence of more than 20%. Sex and gender
      related differences in depression are well described in HIV-negative populations,
      demonstrating that more women are being affected. So far little is known about
      frequency and characteristics of depression in HIV-positive men and women.
      MATERIALS AND METHODS: Primary objective of our prospective epidemiological study
      was the evaluation of the Beck score for depression in male and female patients
      of the Frankfurt HIV Cohort. The Beck Depression Inventory (BDI-II) is a self
      report symptom inventory made up of 21 questions, each with 4 possible answers,
      correlating with a certain point value. INTERPRETATION: score 14-19: mild
      depression; score 20-28: moderate depression; score >=29: severe depression.
      Secondary objectives of the analysis were factors that might possibly influence
      the disposition for depression in HIV-positive patients, e.g. age, antiretroviral
      treatment history, co-morbidities and socioeconomic status. RESULTS: Between
      January and October 2013, 348 patients were enrolled in the study, 161 women and
      187 men of the Frankfurt HIV Cohort, who had a routine appointment at the HIV
      Center of the University Clinic Frankfurt. The mean age of all study participants
      was 45 years (range 22-80). The majority of patients were on antiretroviral
      therapy (91%) at study entrance. The median BDI-II score in all patients was 8 (0
      49); in female patients 10 (0-42), in male patients 6 (0-49), respectively (Table
      1). Significant more women than men showed a score for moderate depression
      (p=0.006). Factors associated with a BDI-II score >=20 in women were older age
      (>45 years), living alone, unemployment and the number of prior changes in
      antiretroviral therapy. CONCLUSIONS: Depression in people living with HIV shows
      sex and gender-related differences that might also influence antiretroviral
      treatment strategies. HIV specialists should be aware of these gender-specific
      aspects and consider routine screening for depression especially in female
      patients of older age or those with multiple therapy changes in history.

PMID- 25397467
TI  - Lp-PLA2 levels in HIV-infected patients.
AB  - INTRODUCTION: HIV-infected patients show an increased risk of cardiovascular
      disease (CVD). In the general population, lipoprotein-associated phospholipase A2
      (Lp-PLA2) appears to be an independent predictor of CVD. We aimed to study
      associations between Lp-PLA2 plasma levels and other risk factors for CVD in HIV
      patients. MATERIALS AND METHODS: A cross-sectional, comparative study of two
      series of cases (HIV patients, n=116 and age-matched non-HIV healthy controls,
      n=113) was conducted. Eighty-seven percent HIV patients on antiretroviral therapy
      (ART), 72.4% with HIV-1 viral load <50 cop/mL. Inflammatory biomarkers (CRP, Lp
      PLA2) and internal carotid intima-media thickness (IMT) were measured and CVD
      risk (Framingham and SCORE algorithms) was calculated. Univariate and
      multivariable associations between these variables were performed. RESULTS: HIV
      patients presented higher Lp-PLA2 levels [276.81 ng/mL (209.71-356.58)] than
      uninfected healthy controls [220.80 ng/mL (172.70-256.90)], p<=0.01. In
      univariate analysis of the global sample, only cigarette smoking was associated
      with higher Lp-PLA2 levels, p<=0.001. In HIV group, female and smoker patients
      showed higher Lp-PLA2 levels, p<=0.05. No significant association was found
      between Lp-PLA2 levels and another CVD risk factors, carotid IMT, Framingham and
      SCORE algorithms, ART, HIV-1 viral load neither and CD4+ T lymphocyte count. In
      multivariate analysis, cigarette smoking remained significantly associated with
      Lp-PLA2 levels [beta=64.8 (95% CI 10.8-118.9) ng/mL, p=0.020]. CONCLUSIONS: HIV
      infected patients present higher Lp-PLA2 levels than healthy controls, and in
      this population, tobacco smoking is significantly associated with increased Lp
      PLA2 levels. Smoking cessation should be a priority in CVD prevention in HIV
      infected patients.

PMID- 25397468
TI  - Liver fibrosis is associated with cognitive impairment in HIV-positive patients.
AB  - INTRODUCTION: The aim of our study was to investigate the potential relationship
      between liver fibrosis (LF) and cognitive performance in HIV+ patients. MATERIALS
      AND METHODS: We performed a cross-sectional cohort study by consecutively
      enrolling HIV+ patients during routine outpatient visits at two clinical centres
      in Italy. Subjects with decompensated liver disease were excluded. All subjects
      underwent a comprehensive neuropsychological battery exploring memory, attention,
      psychomotor speed and language; cognitive impairment was defined as at least two
      abnormal [1.5 SD below the mean for appropriate norms] cognitive domains. LF was
      explored by calculating FIB4 index; in a subgroup of patients, LF was also
      assessed by transient elastography. Factors associated with cognitive impairment
      were investigated by logistic regression models. RESULTS: A total of 413 patients
      [77% males, median age 46 (IQR 39-52), 17% with past AIDS-defining events, 19%
      past IDU, 3% with diabetes, 94% on cART, 90% with HIV RNA <50 copies/mL, 18% co
      infected with HCV] were enrolled. Seventeen patients (4%) had FIB4 >3.25 and
      14/129 (3%) had liver stiffness >14KPa. Forty-seven patients (11%) were diagnosed
      with cognitive impairment. At multivariate analyses patients with FIB4 >1.45
      showed a higher risk of cognitive impairment in comparison with those with lower
      values (OR 2.19, 95% CI 1.02-4.72; p=0.044) after adjusting for education (OR
      0.79, 95% CI 0.71-0.88; p<0.001), past IDU (OR 1.69, 95% CI 0.67-4.23; p=0.264),
      diabetes (OR 2.35, 95% CI 0.62-8.86; p=0.207), HIV RNA <50 copies/mL (OR 0.47,
      95% CI 0.19-1.14; p=0.095) and HCV co-infection (OR 0.88, 95% CI 0.33-2.39;
      p=0.807). Analyzing any single cognitive domain, a higher risk of abnormal
      psychomotor speed was associated with fibroscan score >14KPa in comparison with
      fibroscan score <7KPa (OR 285.07; 95% CI 2.42-33574.06; p=0.020) after adjusting
      for education (OR 0.54, 95% CI 0.31-0.92; p=0.024), age (for 10 years increase)
      (OR 2.03, 95% CI 0.55-7.53; p=0.288), past IDU (OR 4.43, 95% CI 0.35-7.57;
      p=0.526), HIV RNA <50 copies/mL (OR 0.01, 95% CI 0.00-0.18; p=0.003), HIV history
      (for 1 year increase) (OR 0.96, 95% CI 0.83-1.12; p=0.641), CD4 cells count at
      nadir (OR 1.10, 95% CI 0.56-2.16; p=0.779), and HCV co-infection (OR 0.06; 95% CI
      0.00-1.93; p=0.113). CONCLUSIONS: In HIV-infected patients higher LF, estimated
      through non-invasive methods, is associated to a higher risk of cognitive
      impairment.

PMID- 25397469
TI  - The CD4:CD8 ratio is associated with IMT progression in HIV-infected patients on
      antiretroviral treatment.
AB  - INTRODUCTION: Inversion of the CD4:CD8 ratio (<1) has been identified as a
      hallmark of immunosenescence and an independent predictor of mortality in the
      general population. We aimed to assess the association between the CD4:CD8 ratio
      and intima-media thickness (IMT) progression in treated HIV-infected patients as
      a marker of early atherosclerosis. MATERIALS AND METHODS: A longitudinal study
      during three years was conducted in 120 HIV-infected patients receiving
      antiretroviral treatment (ART). We analyzed the associations between the CD4:CD8
      ratio, cardiovascular risk factor and antiretroviral (ARV) treatment and
      progression of subclinical atherosclerosis assessed using carotid IMT at baseline
      and after three years. RESULTS: Finally, 96 patients completed the study. Seventy
      six (79.1%) patients were male, aged 44+/-10 years, 39 (40.6%) were on treatment
      with Protease inhibitors, 49 (51.04%) with non-nucleoside reverse transcriptase
      inhibitors (NNRTI), 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc
      and 2 (2.08%) only with nucleoside reverse transcriptase inhibitors (NRTI). The
      mean of ARV exposition was 6.9+/-5.9 years. Twenty six (27 %) patients had family
      history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%)
      hypertensive, 4 (4.16%) type 2 diabetes, 23 (23.9%) with dyslipidemia and 31
      (32.3%) were infected with C hepatitis virus. Baseline IMT was significantly
      associated with age (rho=0.497; p<0.001), basal glucemia (rho=0.323; p=0.001),
      triglycerides (rho=0.232; p=0.023), Framingham score (rho=0.324; p=0.001),
      CD4:CD8 ratio (rho=-0.176; p=0.05) and dyslipidemia (0.72+/-0.16 mm vs 0.63+/
      0.11 mm; p=0.029). In multivariable analysis where cardiovascular risk factor and
      ARV were included, IMT progression was inversely associated with CD4:CD8 ratio
      (OR=0.283; CI 95% 0.099-0.809; p=0.019) and treatment with NNRTI (OR=0.283; CI
      95% 0.099-0.809; p=0.019). CONCLUSIONS: The inversion of CD4:CD8 ratio in treated
      HIV-infected patients is independently associated with IMT progression, a marker
      of age-associated disease. Therefore, it might be clinically useful as predictor
      of cardiovascular events. Surprisingly, there was a positive correlation between
      receiving NNRTI and progression of IMT.

PMID- 25397470
TI  - HIV-1 tat and rev upregulates osteoclast bone resorption.
AB  - INTRODUCTION: Disruption in bone homeostasis with increased osteoclastic
      resorption may lead to osteoporosis. HIV tat has been found to increase
      differentiation of precursor cells into osteoclast (OC) (1). Presence of soluble
      HIV proteins in virally suppressed HIV patients on ART may drive a bone
      resorption phenotype. We investigated the role of soluble HIV proteins (tat,
      gp120 Mn and Bal, rev and p55-gag) on osteoclastogenesis and OC resorptive
      capacity. METHODS: Mouse monocyte RAW 264.7 cells were cultured in vitro and
      induced to differentiate into OCs with 50 ng/mL RANKL and 25 ng/mL mCSF. Medium
      was supplemented with 100 ng/mL of recombinant HIV tat, gp120 (Mn and Bal), rev,
      nef and p55-gag, respectively, with zolendronate as negative control.
      Differentiated OCs were stained for TRAP and counted. OC resorption function was
      examined by culturing differentiated OCs (in the presence of respective HIV
      proteins) on dentin-coated plates and examining the following (i) sealing zone
      formation, (ii) volume of resorption pits and (iii) area of resorption pits per
      field using confocal microscopy. Expression of OC specific genes including NFATc1
      and cathepsin K was investigated by qPCR. Reactive oxygen species (ROS)
      production is essential in RANKL-induced OC differentiation (2),3; effect of
      these proteins on ROS production was assessed using the fluorescent H2DCFH-DA.
      Mean fluorescence intensity was then measured by flow cytometry. TNFalpha
      production by OC precursors when incubated with tat and rev was measured by
      ELISA. RESULTS: Tat and rev treatment was associated with increased OC formation
      by 70 and 26%, respectively (p<0.01), relative to control, while zolendronate
      significantly inhibited OC formation by 75%. Gp120 Mn and Bal, nef and p55-gag
      treatment had no effect on OC differentiation. Interestingly, neither tat nor rev
      treatment caused significant increases in sealing zone formation but increased
      dentin resorption pit area by 28 and 19%, respectively, and resorption pit volume
      by 11 and 6%, respectively. Tat protein treatment was associated with
      upregulation of NFATc1 and cathepsin K mRNA expression by 20 and 15%,
      respectively. Incubation with tat and rev led to a dose-dependent increase in
      intracellular ROS production in the monocytes and OC precursors and significant
      upregulation in TNFalpha cytokine production by the OC precursors. CONCLUSIONS:
      In addition to their effect of OC differentiation, we demonstrated the effects of
      tat and rev on OC resorption. HIV tat and rev are both biologically active in
      driving a pro-osteoclastic phenotype.

PMID- 25397471
TI  - Tackling cardiovascular co-morbidities in HIV-positive patients: who, how and
      where?
AB  - INTRODUCTION: Cardiovascular disease (CVD) is a significant cause of non-AIDS
      related morbidity and mortality in HIV-positive individuals [1]. Management of
      CVD and associated risk factors in HIV are complicated by drug interactions [2].
      Optimal management can require specialist input. A previous cohort review
      highlighted CVD, comorbidity and cardiovascular (CV) risk in our patients [3]. In
      response, a combined HIV and cardiovascular monthly clinic was established: an
      HIV consultant works in real time with a cardiologist. The clinic manages CV
      disease, complex CV co-morbidities e.g. refractory hypertension, hyperlipidaemia,
      and assesses primary prevention. A dietician works alongside the clinic. AIMS:
      Describe the clinic caseload; record clinic interventions and outcomes; recommend
      service development. MATERIALS AND METHODS: We conducted a retrospective notes
      review of patients attending the co-morbidity clinic from January 2012 to May
      2014. DATA COLLECTED: demographic, HIV, CVD, CV risk, investigations and clinical
      interventions. RESULTS: From a cohort of approximately 960 patients (70%
      African), 60 (6%) were seen in the co-morbidity clinic over the specified time
      period. Median age was 53 (range 24-80). Although 60% of our cohort is female,
      43% (26/60) of the CVD clinic were female. 42 (70%) were African. The mean CD4
      was 560 (range 48-1339). All patients were on ART and 6 (10%) had a detectable
      viral load > 400 copies/mL. Clinic caseload: i) CVD: 9 had a prior CV event (ACS
      or CVA); 5 had CCF; new diagnoses included LVH (2), cardiac dysfunction (6); AF
      (2); atrial thrombus (1). ii) Co-morbidities: 48(80%) had hypertension - 10
      (16.6%) were on quadruple therapy; 17 (28%) had diabetes; 35 (58%) were on a
      statin. Three had their smoking status clearly documented. Seventeen (28%) were
      referred to the dietician. Investigations included echo, 24-hour BP/ tape, CT
      angio, cardiac MR. CONCLUSIONS: The joint clinic facilitated real-time decision
      making on clinical interventions. Patient access to cardiac investigations was
      expedited. Patients attended fewer outpatient appointments. Both cardiology and
      HIV clinicians preferred the benefits of joint working. Clinical outcomes were
      difficult to assess and will need further definition. Recommendations for
      development include: improved CV risk assessment, improved outcome measures,
      links to smoking cessation services.

PMID- 25397472
TI  - Improvement of endothelial function after switching previously treated HIV
      infected patients to an NRTI-sparing bitherapy with maraviroc.
AB  - INTRODUCTION: Nucleoside reverse transcriptase inhibitor (NRTI) is associated
      with endothelial dysfunction and proinflammatory effects. Maraviroc (MVC) is an
      antagonist of CCR5 receptor. CCR5 is the receptor of RANTES (Regulated on
      Activation, Normal T Cell Expressed and Secreted), a mediator of chronic
      inflammation and endothelial function. Our aim was to evaluate the maintenance of
      viral suppression and improvement of endothelial function in virologically
      suppressed HIV-infected patients switched to an NRTI-sparing combined
      antiretroviral therapy (cART) with MVC. MATERIALS AND METHODS: This
      observational, non-interventional, multicenter study was performed at the
      Infectious Diseases Service of Santa Lucia, Morales Meseguer, Virgen de la
      Arrixaca and Reina Sofia University Hospital (Murcia, Spain). The selection
      criteria were to be asymptomatic on a regimen with undetectable viral load (<50
      HIV-RNA copies/mL) for at least six months, no previous treatment with R5
      antagonists, no evidence of previous protease inhibitor (PI) failure and
      available R5 tropism test. Twenty-one HIV-infected patients were selected after
      the treatment regimen was changed to Maraviroc 150 mg/once daily plus ritonavir
      boosted PI therapy. Endothelial function was prospectively evaluated through flow
      mediated dilatation (FMD) of the brachial artery at baseline and at weeks 24.
      RESULTS: We included 21 patients on treatment with PI in combination with 2 NRTI.
      The mean cART exposition was 133+/-68.9 months. Fourteen (66.6%) were males, aged
      49+/-9 years, 15 (71.4%) smokers, 4 (19.04%) family history of coronary heart
      disease, 1 (5.76%) type 2 diabetes and 3 (14.28%) hypertensive, mean total
      cholesterol was 185.5+/-35 mg/dL, c-LDL 100.2+/-37 mg/dL, tryglicerides 170.42+/
      92.03 mg/dL, cHDL 52.6+/-15.5 mg/dL, CD4 779,5+/-383.28 cells/mL, nadir CD4
      187,96+/-96 cells/mL. After 24 weeks of follow-up of a switch to an NRTI-sparing
      regimen, 95.2% of HIV-patients on viral suppressive cART maintained viral
      suppression and CD4+ T cell count. This cART switch improve endothelial function
      in patients with lower baseline FMD levels after 24 weeks (baseline FMD -1.19+/
      4.84 % to 24 weeks FMD 11.32+/-7.27%; p=0.002). CONCLUSIONS: The results of our
      study show that a switch to an NRTI-sparing bi-therapy with MVC improves
      endothelial function and maintained the immune-virologic efficacy. This regimen
      emphasizes the needs for further clinical studies to associate these achievements
      with the incidence of non-AIDS-defining illnesses.

PMID- 25397473
TI  - Mediterranean diet: the impact on cardiovascular risk and metabolic syndrome in
      HIV patients, in Lisbon, Portugal.
AB  - INTRODUCTION: Metabolic syndrome (MS) is common in HIV-infected individuals and
      it is associated with higher cardiovascular risk (CVR). Mediterranean diet has
      been associated with a better metabolic control and lower CVR. MATERIALS AND
      METHODS: From December 2013 to May 2014, individuals between 18 and 65 years of
      age, who attended the outpatient HIV Clinic at the University Hospital Santa
      Maria, Lisbon, were selected. Adherence to Mediterranean diet was evaluated with
      MedDietScore, a scale from 0 to 55 that punctuates 11 food items according to the
      frequency of intake. Higher scores represent higher adherence. CVR was assessed
      using D.A.D tool (classified as low, moderate or high risk). We excluded
      individuals with opportunistic disease, hospitalized in the past three months or
      with renal disease diagnosis. All participants gave written informed consent.
      RESULTS: In the 571 HIV patients included, 67.1% (n=383) were male, 91.6% (n=523)
      Caucasian, with a mean age of 46.5+/-8.9 years. Patients were divided in two
      groups: naive (7.5%; n=43) or on antiretroviral treatment (ART) (92.5%; n=528).
      Mean length of HIV diagnosis was 6.7+/-6.5 years (naive) and 13.3+/-6.1 years
      (ART); TCD4+ counts were above 500 cel/mm3 in 55.8% (n=24) and 67.6% (n=357) of
      the patients, respectively. MS was present in 33.9% (n=179) of patients in ART
      group and 16.3% (n=7) in naive group. Presence of MS was associated with ART
      group (OR=2.7; p=0.018). MS was also associated with older age in this group
      (p=0.000). Overall, mean MedDietScore was 27.3+/-5.5. Higher score was associated
      with older age (r=0.319; p=0.000). Naive patients presented a trend to higher
      adherence to Mediterranean diet (65.1% vs 51.7% in naive group; p=0.090). No
      relation between MS and Mediterranean diet was found. Higher CVR was associated
      with the presence of MS in the ART group (p=0.001). In this group, individuals
      with moderate CVR presented higher rates of adherence to Mediterranean diet
      (p=0.036) when compared to low and high CVR score. CONCLUSIONS: In this cross
      sectional study, naive individuals presented a trend to higher adherence to
      Mediterranean diet. On the ART group, higher adherence to Mediterranean diet was
      found in individuals with moderate CVR score. We think that this might suggest
      that this group of patients adopt this diet only in the presence of metabolic
      alterations or perceived CVR. Prospective studies in HIV patients are required to
      determine the impact of adherence to Mediterranean diet on the reduction of CVR.

PMID- 25397474
TI  - Research on demands and accessibility of health services for AIDS long-surviving
      patients with AIDS-nonrelated diseases: a survey in central China.
AB  - INTRODUCTION: Compared with western countries, China started to provide free
      medicine for AIDS patients years later, which leads to the late emergence of
      problems on health service demands of AIDS long-surviving patients with non-AIDS
      related diseases. Government hasn't laid enough stress on it. MATERIALS AND
      METHODS: The interviews and questionnaire surveys are conducted and analyzed to
      get information. The interviewees include 81 AIDS long-surviving patients in
      three villages and several hospitals in Shangcai, Zhumadian, and 18 AIDS-related
      decision makers and health service providers. RESULTS: There are 79 long
      surviving patients out of 81. 58 patients have non-AIDS-related diseases. 21
      patients get hypertension and 28 get HCV. 100% patients have been to the clinics
      with their real-name IC cards for minor illness. 43 patients have been
      transferred to assigned hospitals at the county level. Seven have the experience
      utilizing health services in the municipal or provincial assigned hospitals. The
      problem is on accessibility. 40 patients hope to get more convenient and cheap
      health services. Among them, 37 say the kinds and the amount of medicine in
      village clinics are not adequate. Seven give up because of the expensive
      treatment expense. For 21 patients with hypertension, 3 buy medicine at the
      county-level hospitals. The other 18 choose to buy at private pharmacy. For 28
      patients with HCV, 3 are not aware they actually got HCV. Free hepatic protector
      medicine is provided at village clinics. Up to 11 patients have not taken any
      treatment for HCV. CONCLUSIONS: Patients with hypertension go to the private
      pharmacy for medicine instead of higher level hospital because of lack of
      medicine in clinics, far distance from hospitals, cumbersome procedures in
      hospitals, limited dosage of prescriptions and too little discount. The situation
      for patients with HCV is even worse. It is predicted 70% of AIDS long-surviving
      patients have HCV. The treatment is expensive and out of pocket. And free liver
      protection medicine does not work sometimes. Some patients working outside their
      home town do not want to reveal their health situation to get free medicine. The
      elderly with multiple co-morbidities need more caring. Government should expand
      the scale of free medicine. Hospitals need to improve medicine plans and assist
      on medicine purchase. For patients, attitude decides everything.

PMID- 25397475
TI  - Smoking prevalence, readiness to quit and smoking cessation in HIV+ patients in
      Germany and Austria.
AB  - INTRODUCTION: Due to the interaction between smoking and the virus and the
      antiretroviral therapy, the excess health hazard due to smoking is higher in HIV+
      patients than in the general population. International studies suggest a higher
      prevalence of smoking in HIV+ subjects compared to the general population. It was
      the aim of the study to assess prevalence of smoking, to analyze determinants of
      smoking, and to evaluate readiness to quit in HIV+ patients in Germany and
      Austria. MATERIAL AND METHODS: Consecutive patients with positive tested HIV
      status, smokers and non-smokers, who are treated in seven different HIV care
      centres in Austria and Germany were included. Nicotine dependence was assessed
      with the Fagerstrom Test for Nicotine Dependency (FTND), and stages of change by
      a standardized readiness to quit questionnaire. Self-reported smoking status was
      objectified by measuring exhaled carbon monoxide levels. Smokers who wanted to
      quit were offered a structured smoking cessation programme, and those who did not
      want to quit received a 1-minute consultation. After six months, the smoking
      status of all included subjects was reassessed. RESULTS: A total of 447 patients
      were included; the response rate was 92%. Prevalence of smoking was 49.4%.
      According to a multivariate logistic regression analysis, lower age, male sex,
      lower educational level, and smoking of the partner were significantly associated
      with the smoking status. According to the FTND, 25.3% showed a low (0-2 points),
      27.6 a moderate (3-4 points) and 47.1% a high (5-10 points) dependency. Regarding
      stages of change, 15.4% of the smokers were in the stadium precontemplation, 48.4
      in contemplation, 15.4 in preparation and 10.0 in the stadium action. 11.0% were
      not assignable in any stadium. Higher education level and lower grade of
      dependency were significantly associated with the wish to quit smoking. Six
      months after the baseline examination, smoking cessation visits (at least one
      session) was performed in 28.5% of the smokers. 13% of the smokers have quit
      smoking, 23% have reduced smoking and 63% did not change smoking habits
      positively 6 months after the first visit. CONCLUSIONS: Prevalence rates for
      smoking in HIV+ subjects are higher than in the general population. Readiness to
      quit is, however, high, and 13% of smokers who have quit smoking after six months
      is a remarkable short-term success. This observation underlines the importance
      and feasibility of addressing smoking habits in HIV care.

PMID- 25397476
TI  - Two years of Truvada for pre-exposure prophylaxis utilization in the US.
AB  - INTRODUCTION: Truvada(r) (TVD) was approved in July 2012 by the US FDA for pre
      exposure prophylaxis (PrEP) in combination with safer sex practices to reduce the
      risk of sexually acquired HIV-1 in high-risk adults. This study explores the
      characteristics of US PrEP users and their prescribers over the past two years.
      MATERIALS AND METHODS: A previously described algorithm was used to identify TVD
      for PrEP by excluding use for HIV treatment, post-exposure prophylaxis, and off
      label treatment of chronic hepatitis B. National electronic patient level data
      from ~55% of all US retail pharmacies that dispensed TVD between January 1, 2012
      and March 31, 2014 was collected. De-identified patient-level data including
      prescription refill data, medical claims and patient demographics were analyzed
      via logistic regression to estimate the odds of change by year. RESULTS: A total
      of 3253 unique individuals who started TVD for PrEP between January 1, 2012 and
      March 31, 2014 were included in this analysis. Women comprised 42.0% of PrEP
      users. Although mean age was 38.1+11.9 years, with males being significantly
      older (39.3+11.6) than females (36.4+12.3), 11.5% of individuals were under 25
      years old. The proportion of males under 25 was 7.4% (95% CI 6.3-8.7);
      significantly lower than that of women, 17.2% (95% CI 15.3-19.3). New starts have
      increased from 293 in 2012 to 472 Q1 2014. During the 12-month period ending
      March 31, 2013 and March 31, 2014 the number of new starts among females dropped
      from 44.5% to 22.9%. CONCLUSIONS: The population of TVD for PrEP users in the US
      nationally appears to be shifting demographically. It continues to be initiated
      mostly by primary care providers. Over a two-year period new starts of Truvada
      for PrEP have increased considerably among males. While the overall proportion of
      female users decreased between Q1 2012 and Q1 2014, females that started on PrEP
      are younger than males. More community-level data on PrEP usage will be helpful
      in informing local efforts to integrate PrEP in HIV prevention messaging and
      services.

PMID- 25397477
TI  - Failure of daily tenofovir to prevent HIV transmission or the establishment of a
      significant viral reservoir despite continued antiretroviral therapy.
AB  - INTRODUCTION: Truvada is licenced for HIV-1 prevention in the USA and is
      available in the private sector. Tenofovir performed as well as Truvada in the
      PARTNERS PrEP study and is used as HIV pre-exposure prophylaxis (PreP) in some
      settings. The clinical efficacy of Tenofovir for PrEP outside a clinical trial is
      unknown. Antiretroviral therapy (ART) at acute HIV-1 infection (AHI) limits the
      size of the reservoir, optimizing the chance of maintaining viral control off
      therapy. As such ART at acute HIV infection is proposed to offer a functional
      cure in a minority of subjects. We present two cases where Tenofovir PrEP failed
      to prevent HIV acquisition and failed to limit viral reservoir. MATERIALS AND
      METHODS: Two individuals receiving tenofovir monotherapy for Hepatitis B
      monoinfection were diagnosed with AHI as defined by a negative HIV antibody test
      within three months of a positive HIV test following unsafe sex with casual male
      partners. In-depth histories were taken. Viral genotypes and Tenofovir drug
      levels were measured from samples taken as close to HIV seroconversion as
      possible and subsequent samples were analyzed for proviral Total HIV-1 DNA by
      qPCR. RESULTS: Patient A had received tenofovir for the preceding six years and
      always maintained an undetectable Hepatitis B viral load with no concerns about
      adherence. Two weeks preceding the positive HIV antibody test, he experienced
      mild symptoms (fever, pharyngitis) of HIV seroconversion. HIV status was
      confirmed by a repeat fourth generation HIV antibody test and by Western Blot and
      an HIV viral load was undetectable. Tenofovir trough level at HIV diagnosis was
      within normal limits. The regimen was intensified to Eviplera and a total HIV-1
      DNA was 1381 copies/million CD4 T cells. Patient B received four regimens for
      hepatitis B treatment before starting tenofovir monotherapy in 2011 and
      subsequently maintained an undetectable hepatitis B viral load. After three years
      of tenofovir monotherapy he developed a severe symptomatic seroconversion illness
      and tested HIV antibody positive. The baseline HIV viral load was 103,306
      copies/mL. The regimen was intensified and total HIV-1 DNA was 2746
      copies/million CD4 T cells. CONCLUSIONS: Further investigation into the efficacy
      of tenofovir for PrEP outside a clinical trial is required. ART at AHI does not
      always lead to a low viral reservoir. To explore the possibility of replication
      incompetent virus, viral outgrowth assays are underway.

PMID- 25397478
TI  - Attitudes and beliefs towards early ART initiation in MSM with primary HIV
      infection.
AB  - INTRODUCTION: ART initiation in primary HIV infection (PHI) could reduce risk of
      transmission to sexual partners at a time of high viraemia, although health
      benefit for the individual remains unknown. We examined attitudes to early ART
      and associated beliefs in men who have sex with men (MSM) with PHI. MATERIALS AND
      METHODS: Semi-structured face-to-face in-depth interviews were conducted with 13
      MSM aged >=16 years attending a central London HIV clinic, within 12 months of
      date of estimated HIV seroconversion. Audio recordings of interviews were
      transcribed verbatim and analyzed thematically. RESULTS: Median age was 33 years
      (range 22-47), majority were white British (n=8), educated to university level
      (n=11) and were not on ART (n=10). Great diversity in ART knowledge and
      expectations around starting were observed, with some men assuming they would be
      prescribed ART immediately upon diagnosis. Deferral until CD4<350 came as a
      surprise and counterintuitive when put into the context of treating other
      diseases. For many, the decision to start ART was a balance of current and future
      health and quality of life. Fear of side effects was prevalent, with many
      believing them inevitable and a reason to avoid early ART. A perceived lack of
      "good quality" evidence showing a health benefit of early ART caused confusion.
      Avoiding the decision to start or deferring to their HIV clinician was common,
      however reported clinicians' views also varied. Some men voiced a desire to be
      proactive and start early ART to control viral replication. In these cases men
      also reported a belief that ART could be temporary as they expected a cure in
      their lifetime. Men commonly described feeling "infected" and reducing this
      infectiousness was seen as a major benefit of ART; not purely to reduce the risk
      of transmission to sexual partners but to facilitate disclosure to partners,
      reduce anxiety and guilt and restore sexual confidence commonly lost after HIV
      diagnosis. Having a long-term HIV-negative partner was a strong facilitator to
      starting ART to reduce transmission in the absence of good evidence of individual
      health benefit. CONCLUSIONS: Factors involved in the decision to start ART in PHI
      were complex. Uncertainty over individual health benefits in conjunction with
      fear of toxicities were barriers to starting ART early. By contrast ART was seen
      as a facilitator to disclosure, and as a way to limit the consequences of
      infection until a cure is found.

PMID- 25397479
TI  - The suspected unexpected and serious adverse events of antiretroviral drugs used
      as HIV prophylaxis in HIV uninfected persons.
AB  - INTRODUCTION: With increased usage of antiretroviral drugs (ARVs) in HIV
      uninfected persons proper reporting on suspected unexpected serious adverse
      reactions (SUSARs) and continued insight into serious adverse events (SAEs) is
      needed for adequate information on ARVs safety in such populations. METHODS: We
      have evaluated medical documentation of persons receiving ARVs after non
      occupationally HIV exposure (nPEP) during five concomitant years (2009-2013).
      SAEs and SUSARs were evaluated by two HIV physicians and defined according to
      international standards. In statistical methods, Kaplan Meier survival analysis
      was used to estimate the probability of SAE and Cox proportional hazard models to
      identify independent predictors of developing SAE. Only the first SAE was
      included in these analyses. RESULTS: In total, 375 persons received nPEP. The
      most common reason was needle stick (43%), followed by unprotected sexual
      intercourse (17%), rape (10%) and first aid (10%). In 84 (22%) cases, the source
      patient was either known to be HIV positive or within a high risk group (active
      injecting drug user). In total, 170 SAEs were reported, 139 persons had only one
      SAE and majority developed it within first two weeks. The most frequent first
      SAEs were gastrointestinal disorders (22%), followed by general symptoms (9%),
      hypersensitivity reactions (1.6%) and CNS symptoms (1.3%). The remaining events
      were laboratory abnormalities of liver and kidney function, haematological
      disorders, other and unknown, each contributing to less than 1% of all patients.
      8 (2.1%) patients have developed a SUSAR (bradycardia, vivid dreams,
      lymphadenopathy of the neck, increased platelet count, swelling and pain of large
      joints, swelling of lower limbs, peripheral oedema and loss of concentration). 22
      (5.9%) persons discontinued nPEP due to adverse event and 19 (5.1%) required a
      paid sick leave from work. In multivariate analyzes, only age was independent
      predictor of developing SAE (HR 1.17; [95% CI 1.03-1.34]; p=0.02). CONCLUSIONS:
      In our observation, SAEs in reaction to nPEP were frequent yet usually mild
      events, mostly occurring in first two weeks and rarely causing discontinuation.
      The only significant factor increasing the risk of SAE was age. SUSARs were rare
      and moderately significant. More insight into this important area is required in
      order to ascertain proper pharmacovigilance of ARVs usage in HIV uninfected
      persons.

PMID- 25397480
TI  - Acceptability of PrEP among HIV negative Portuguese men who have sex with men
      that attended 2014 Lisbon pride fair.
AB  - INTRODUCTION: Consistent use of PrEP reduces HIV transmission from sexual
      practices amongst men who have sex with men (MSM) up to 92% [1]. Lisbon MSM
      cohort study estimates point that 59.3% of their participants at entrance (1593
      HIV negative MSM enrolled between April 2011 and May 2013) were eligible for PrEP
      [2], according to the 2014 USA PrEP guidelines [3]. Studies about PrEP
      acceptability and implementation support policies aimed at increasing and rolling
      out its use. Hence, the exploratory study about PrEP acceptability in MSM at
      Lisbon. MATERIALS AND METHODS: A street-based intercept survey, adapted from
      Mantell et al. study [4], was the one used on MSM attending the 2014 Lisbon pride
      fair. The survey included socio-demographic data, PrEP awareness and readiness to
      use it, probability of MSM's social network to also use it, promptness to join
      PrEP-related studies, type of PrEP warranted and condomless anal sex practice in
      the last six months. RESULTS: A total of 110 HIV negative Portuguese MSM
      responded, with a median age of 33% and 84% of them identified themselves as gay.
      A majority of MSM were unaware of PrEP (59%); those that were aware, had heard of
      it trough CheckpointLx (31%), internet (22%) or health professionals (20%). 66%
      were likely or very likely to participate in PrEP-related studies. 57% of MSM
      were likely or very likely to use PrEP if available and reported that some, if
      not almost all of their social network, will do it too (70%). Type of PrEP
      preferred was oral, a pill a day (43%), followed by oral, intermittent intake
      (32%). Overall 41% of MSM had condomless anal sex practice in the last six
      months. CONCLUSIONS: In this MSM Portuguese sample, a general willingness to
      adopt PrEP was predominant, specially the oral daily intake. Forty-one percent of
      participants had had condomless anal sex practice in the last six months and
      therefore fitted within the criteria to be on Pre-Exposure Prophylaxis (PrEP),
      according to MSM Risk Index in 2014 USA PrEP guidelines. PrEP, when available in
      Portugal, should be a powerful tool for HIV prevention in this key population.

PMID- 25397481
TI  - Safety, tolerability and effectiveness of HIV non-occupational prophylaxis in
      Taiwan.
AB  - INTRODUCTION: Increasing numbers of new HIV infection is an important issue of
      public health in Taiwan. We aim to evaluate the safety, tolerability and
      effectiveness of HIV non-occupational prophylaxis (nPEP) in Taiwan. MATERIALS AND
      METHODS: We conducted a prospective cohort observational study between March 2011
      and May 2014. Three-combined antiretroviral agents were prescribed for all the
      persons who sought for HIV post-exposure prophylaxis after high risk sexual
      behaviour. HIV screening, health education and consultation were done before
      initiation of nPEP. Adverse effects were evaluated at Weeks 1, 2 and 4 and
      effectiveness was evaluated at Weeks 12 and 24. We also assessed adherence by
      pill count and regimen completion rates. RESULTS: During the study periods, 255
      persons were enrolled. Among the enrolled cases, 43.9% (112/255) of them received
      zidovudine (AZT)-based regimen while the others received tenofovir (TDF)-based
      regimen and the third agent was composed of mostly lopinavir/ritonavir (81.4%).
      The completion rate of nPEP was 85.9% (219/255), and discontinuation rate of nPEP
      among AZT-based regimen is higher than TDF-based regimen (17.0% vs 8.2%). Any
      grade adverse effects are higher among AZT-based regimen than TDF-based regimen
      (62.5% vs 32.1%) although most adverse effects were grade 1-2. After a 24-week
      follow-up, only one person experienced HIV seroconversion and he had primary
      syphilis at the moment when he sought for nPEP. CONCLUSIONS: NPEP could be an
      effective prevention method in a part of HIV prevention strategy and TDF-based
      regimen had better tolerability in Taiwan.

PMID- 25397482
TI  - Detection of resistance mutations and CD4 slopes in individuals experiencing
      sustained virological failure.
AB  - INTRODUCTION: Several resistance mutations have been shown to affect viral
      fitness, and the presence of certain mutations might result in clinical benefit
      for patients kept on a virologically failing regimen due to an exhaustion of drug
      options. We sought to quantify the effect of resistance mutations on CD4 slopes
      in patients undergoing episodes of viral failure. MATERIALS AND METHODS: Patients
      from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of
      virological failure (>3 consecutive RNA measurements >500 on ART) with at least
      three CD4 measurements and a resistance test during the episode were included.
      Mutations were identified using the IAS-US (2013) list, and were presumed to be
      present from detection until the end of an episode. Multivariable linear mixed
      models with a random intercept and slope adjusted for age, baseline CD4 count,
      hepatitis C, drug type, RNA (log-scale), risk group and subtype were used to
      estimate CD4 slopes. Individual mutations with a population prevalence of >10%
      were tested for their effect on the CD4 slope. RESULTS: A total of 2731 patients
      experiencing a median of 1 (range 1-4) episodes were included in this analysis.
      The prevalence of any resistance per episode was 88.4%; NNRTI resistance was most
      common (78.5%). Overall, CD4 counts declined by 17.1 (-19.7; -14.5) cells per
      year; this decline was less marked with partial viral suppression (current HIV
      RNA more than 1.5 log below the setpoint; p=0.01). In multivariable models
      adjusting for viral load, CD4 decline was slower during episodes with detected
      resistance compared to episodes without detected resistance (21.0 cells/year
      less, 95% CI 11.75-30.31, p<0.001). Among those with more than one resistance
      mutation, there was only weak evidence that class-specific mutations had any
      effect on the CD4 slope (Table 1). The effects of individual mutations (incl.
      M184V) were explored, but none were significantly associated with the CD4 slope;
      for these comparisons, a Bonferroni-corrected p-value level was 0.003.
      CONCLUSIONS: In our study population, detected resistance was associated with
      slightly less steep CD4 declines. This may be due to a biological effect of
      resistance on CD4 slopes, or other unmeasured factors such as poor adherence
      among individuals without resistance. Among individuals with detected drug
      resistance, we found no evidence suggesting that the presence of individual
      mutations was associated with beneficial CD4 slope changes.

PMID- 25397483
TI  - HIV-1 group O integrase displays lower susceptibility to raltegravir and has a
      different mutational pathway for resistance than HIV-1 group M.
AB  - INTRODUCTION: HIV-1 group O (HIV-O) is a rare HIV-1 variant characterized by a
      high number of polymorphisms, especially in the integrase gene, e.g. positions
      L74I, S153A, G163Q and T206S. As HIV-O integrase enzymes have not previously been
      studied, our aim was to assess the impact of HIV-O integrase polymorphisms on
      susceptibility to integrase inhibitors and emergence of resistance associated
      mutations. Viruses and Methods: We cloned and purified integrase proteins from
      each of HIV-1 Group O clades A (HIV-O/A) and B (HIV-O/B), a HIV-O divergent
      strain (HIV-O/Div), and HIV-1 group M (subtype B, HIV-M/B) and characterized
      these enzymes for susceptibility to integrase strand transfer inhibitors (INSTIs)
      in cell-free assays and in tissue culture, in the absence or presence of varying
      concentrations of several INSTIs. The inhibition constant (Ki) and IC50 were
      calculated and compared for HIV-M and HIV-O integrases. Selections for resistance
      related mutations were performed using cord blood mononuclear cells and
      increasing concentration of INSTIs. RESULTS: HIV-O integrase and viruses were
      more susceptible to raltegravir (RAL) in competitive inhibition assays and in
      tissue culture than were HIV-M enzymes and viruses, respectively. During
      selection, we observed different pathways of resistance depending on the drug and
      clade. Mutations selected in HIV-O can be classified as follows: (1) mutations
      described for HIV-M such as T97A, Q148R, V151A/I (RAL), T66I, E92Q, E157Q (EVG)
      and M50I, R263K (DTG) and (2) signature mutations for HIV-O (i.e. not described
      in HIV-M) F121C (HIV-O/B for RAL), V75I (HIV-O/A for RAL) and S153V (HIV-O/A for
      DTG). Only the HIV-O/Div selected the Q148R mutation for RAL and R263K+M50I for
      DTG, as previously described for HIV-M. None of the HIV-O viruses selected either
      N155H or Y143C. The selection of the specific S153V mutation could be explained
      at the nucleotide level: HIV-O at this position contains an alanine and
      substitution of alanine to valine (153AGGC->153VGTC) is easier than substitution
      of alanine to tyrosine (153AGGC->153YTAC), with only a transversion needed
      instead of one transition plus one transversion. CONCLUSIONS: This is the first
      report of susceptibility and resistance in vitro to INSTIs for HIV-O. Our study
      confirmed the impact of HIV-O polymorphism, on susceptibility to INSTIs and the
      emergence of resistance mutations.

PMID- 25397484
TI  - Protease mutations emerging on darunavir in protease inhibitor-naive and
      experienced patients in the UK.
AB  - INTRODUCTION: Darunavir (DRV) is a preferred agent in treatment guidelines for
      ART-naive and experienced patients [1]. It is considered to have a high genetic
      barrier to resistance and 11 resistance-associated mutations (RAMs) are
      recognized by IAS-USA [2]. These have largely been identified by analyses
      examining the correlation between baseline genotype and virological response [3].
      However, there is little information on RAMs that are directly selected by DRV,
      outside of short-term clinical trials. We aimed to identify emerging mutations by
      comparing the genotypes of individuals before and after DRV exposure. MATERIALS
      AND METHODS: The UK HIV Drug Resistance Database was used to identify patients
      aged over 16 who had received at least 30 days of a DRV-containing regimen.
      Patients were included if they had a "baseline" resistance test, prior to DRV
      exposure, and a "repeat" test, either on DRV or within 30 days of stopping this
      agent. To avoid attributing the effects of other PIs on emerging RAMs to DRV,
      patients were excluded if they had received another PI for greater than 90 days
      between the baseline genotype and the start of DRV. The baseline and repeat tests
      were compared to determine the nature of mutations stratified by PI history.
      RESULTS: A total of 5623 patients had DRV, of whom 306 met the inclusion
      criteria. A total of 228 (74.5%) were male, median age at the start of DRV was 42
      years (IQR 37-47), and half had subtype B infection. The mode of transmission was
      homosexual contact for 50%, heterosexual for 38%, and 3% were injection drug
      users. The median CD4 count at the start of DRV was 257 cells/mm(3) (IQR 94-453).
      A total of 149 patients (49%) had a history of PI use prior to DRV, and 157 (51%)
      were PI-naive. The most common previous PIs were lopinavir, atazanavir, and
      saquinavir. Baseline DRV RAMs were present in 1 (0.6%) PI-naive and 20 (13.4%) PI
      experienced patients. Mutations emerged under DRV pressure in a further 3 (1.9%)
      PI-naive patients, and in 7 (4.7%) PI-experienced patients, 5 of whom had other
      DRV RAMs present at baseline (Table 1). The median time from the start of DRV to
      the repeat test was 196 days for PI-naive patients and 296 days for PI
      experienced. CONCLUSIONS: PI-experienced patients had a greater prevalence of DRV
      RAMs at baseline than PI-naive individuals, probably due to the fact that some
      DRV RAMs can be selected by other PIs. This group also accumulated more RAMs
      during DRV exposure, possibly because previous PIs had caused minority variants
      which then emerged on DRV therapy. Overall, only 10 patients accumulated 16 RAMs,
      which supports the perception that DRV has a high genetic barrier to resistance.
      Repeat genotyping in the case of virological failure on DRV may still be
      warranted to detect emerging resistance and guide management decisions.

PMID- 25397485
TI  - Rilpivirine versus etravirine validity in NNRTI-based treatment failure in
      Thailand.
AB  - INTRODUCTION: Etravirine (ETR) and rilpivirine (RPV) are the second-generation
      non-nucleoside reverse transcriptase inhibitors (NNRTI) for treatment of HIV-1
      infection. Etravirine is recommended for patients with virologic failure from
      first generation NNRTI-based regimen [1]. RPV has profile with similar properties
      to ETR but this agent is approved for treatment-naive patients [2]. In Thailand,
      ETR is approximately 45 times more expensive than RPV. We aimed to study the
      patterns of genotypic resistance and possibility of using RPV in patients with
      virologic failure from two common NNRTI-based regimens: efavirenz (EFV)- or
      nevirapine (NVP)-based regimen. MATERIALS AND METHODS: Data of clinical samples
      with confirmed virologic failure during 2003-2010 were reviewed. We selected the
      samples from patients who failed EFV- or NVP-based regimen. Resistance-associated
      mutations (RAMs) were determined by IAS-USA Drug Resistance Mutations. DUET,
      Monogram scoring system and Stanford Genotypic Resistance Interpretation were
      applied to determine the susceptibility of ETR and RPV. RESULTS: A total of 2086
      samples were analyzed. Samples from 1482 patients with virologic failure from NVP
      based regimen treatment failure (NVP group) and 604 patients with virologic
      failure from EFV-based regimen treatment failure (EFV group) were included. 95%
      of samples were HIV-1 CRF01_AE subtype. Approximately 80% of samples in each
      group had one to three NNRTI-RAMs and 20% had four to seven NNRTI-RAMs. 181C
      mutation was the most common NVP-associated RAM (54.3% vs 14.7%, p<0.01). 103N
      mutation was the most common EFV-associated RAM (56.5% vs 19.1%, p<0.01). The
      calculated scores from all three scoring systems were concordant. In NVP group,
      165 (11.1%) and 161 (10.9%) patients were susceptible to ETR and RPV,
      respectively (p=0.81). In EFV group, 195 (32.2%) and 191 (31.6%) patients were
      susceptible to ETR and RPV, respectively (p=0.81). The proportions of viruses
      that remained susceptible to ETR and RPV in EFV group were significantly higher
      than NPV group (ETR susceptibility 32.2% vs 11.1%, p<0.01, RPV susceptibility
      31.6% vs 10.9%, p<0.01), respectively. CONCLUSIONS: RPV might be a cost saving
      and reasonable second line NNRTI for patients who failed EFV- or NVP-containing
      regimens, especially in resource-limited setting because these two agents have
      comparable susceptibility identified by genotyping. From our study, approximately
      30% of patients who failed EFV-based regimens had viruses that remained
      susceptible to RPV.

PMID- 25397486
TI  - Appearance of NS3 Q80K mutation in HCV genotype 1a mono- or HIV/HCV co-infected
      patients in a Berlin laboratory.
AB  - INTRODUCTION: Simeprevir, a new oral NS3/4A protease inhibitor, was recently
      approved by the FDA and the EMA for the treatment of patients with chronic HCV
      genotype 1, 4, 5 and 6 infection l. It has been recommended in the 2014 UK
      Consensus Guidelines as a possible treatment of previously untreated genotype 1a
      infected patients. The antiviral efficacy of simeprevir is adversely affected by
      the mutation at the Q80K loci. There is controversial discussion that the
      incidence of Q80K in the European HCV 1a-infected community is very low and
      therefore testing of Q80K before starting a therapy including simeprevir is not
      necessary. We analyzed the appearance of Q80K in all sequenced HCV NS3A samples
      in 2014 in our laboratory. MATERIALS AND METHODS: All in 2014 received orders for
      HCV resistance tests were analyzed with an in-house bulk sequencing method
      analyzing NS3A amino acids 1-181. Analysis was performed using geno2pheno HCV.
      The genotype 1a samples were selected, Q80K status and data of HIV co-infection
      were collected. RESULTS: Forty-two HCV 1a samples were sent to us for resistance
      analyses from nine different medical centres in Berlin and Hannover, Germany.
      Nineteen (or 45%) of the sequences showed a Q80K mutation. Six extra clade I
      viruses had no Q80K mutation. Comparison between mono- and HIV-1 co-infected
      patients showed no difference in frequency of Q80K (mono-infected: 8 out of 19
      patients; co-infected: 9 out of 23). For two 80K-positive patients, the HIV
      status was not available. CONCLUSIONS: The incidence for Q80K mutation in HCV
      genotype 1a with overall 45% is substantially high in our cohort and does not
      differ between mono- and HIV-1 co-infected patients. Response to simeprevir is
      affected by the presence of viral Q80K. When treating HCV-infected patients with
      a simeprevir containing regimen, it is therefore important that HCV does not
      contain the Q80K mutation.

PMID- 25397487
TI  - Patterns of drug resistance among newly diagnosed HIV-1 infected patients in
      Greece during the last decade: the crucial role of transmission networks.
AB  - INTRODUCTION: The prevalence of drug resistance is approximately 10% in Europe
      and North America among newly infected patients. We aim to investigate the
      temporal patterns of resistance among drug naive HIV-infected individuals in
      Greece and also to determine transmission networking among those with resistant
      strains. MATERIALS AND METHODS: Protease (PR) and partial reverse transcriptase
      (RT) sequences were determined from 2499 newly diagnosed HIV-1 patients, in
      Greece, during 2003-2013. Genotypic drug resistance was estimated using the
      HIVdb: Genotypic Resistance Interpretation Algorithm. We identified transmission
      clusters of resistant strains on the basis of a large collection of HIV-1
      sequences from 4024 seropositives in Greece. Phylodynamic analysis was performed
      using a Bayesian method. RESULTS: We estimated drug resistance levels among naive
      patients on the basis of all resistance mutations in PR and partial RT. The
      overall prevalence of resistance was 19.6% (490/2499). Resistance to NNRTIs was
      the most common (397/2499, 15.9%) followed by PIs (116/2499, 4.6%) and NRTIs
      (79/2499, 3.2%). We found a significant trend for decreasing resistance to NRTIs
      over time (6.7%-1.6%). There was no time trend for the overall PI and NNRTI
      resistance. The most frequently observed major resistant sites in PR were V82
      (2.0%) and L90 (1.8%). In RT, we found E138 (58.6%), K103 (13.1%), V179 (8.4%)
      and T215 (7.1%), M41 (4.7%) associated with resistance to NNRTIs and NRTIs,
      respectively. The prevalence of K103N and E138Q were significantly increased
      during 2003-2013. Crucially, we found that both K103N, E138Q are associated with
      transmission networking within men having sex with men (MSM) and intravenous drug
      user (IDU) local networks. The K103N network included seropositives across
      Greece, while the latter only from the recent IDU outbreak in Athens metropolitan
      area (1). Phylodynamic analyses revealed that the exponential growth for K103N
      network started in 2009 (Figure 1) and for the E138Q in 2010. CONCLUSIONS: The
      overall resistance has been stable in Greece over time; however, specific NNRTI
      resistance patterns are increasing. Notably, they are associated with local
      transmission networking, thus suggesting that this is the cause for the increased
      patterns of NNRTI resistance and not multiple transmissions of resistant strains
      from different sources among treated individuals. Our study highlights the
      advance of molecular epidemiology for understanding the dynamics of resistance.

PMID- 25397488
TI  - Improved therapy-success prediction with GSS estimated from clinical HIV-1
      sequences.
AB  - INTRODUCTION: Rules-based HIV-1 drug-resistance interpretation (DRI) systems
      disregard many amino-acid positions of the drug's target protein. The aims of
      this study are (1) the development of a drug-resistance interpretation system
      that is based on HIV-1 sequences from clinical practice rather than hard-to-get
      phenotypes, and (2) the assessment of the benefit of taking all available amino
      acid positions into account for DRI. MATERIALS AND METHODS: A dataset containing
      34,934 therapy-naive and 30,520 drug-exposed HIV-1 pol sequences with treatment
      history was extracted from the EuResist database and the Los Alamos National
      Laboratory database. 2,550 therapy-change-episode baseline sequences (TCEB) were
      assigned to test set A. Test set B contains 1,084 TCEB from the HIVdb TCE
      repository. Sequences from patients absent in the test sets were used to train
      three linear support vector machines to produce scores that predict drug exposure
      pertaining to each of 20 antiretrovirals: the first one uses the full amino-acid
      sequences (DEfull), the second one only considers IAS drug-resistance positions
      (DEonlyIAS), and the third one disregards IAS drug-resistance positions
      (DEnoIAS). For performance comparison, test sets A and B were evaluated with
      DEfull, DEnoIAS, DEonlyIAS, geno2pheno[resistance], HIVdb, ANRS, HIV-GRADE, and
      REGA. Clinically-validated cut-offs were used to convert the continuous output of
      the first four methods into susceptible-intermediate-resistant (SIR) predictions.
      With each method, a genetic susceptibility score (GSS) was calculated for each
      therapy episode in each test set by converting the SIR prediction for its
      compounds to integer: S=2, I=1, and R=0. The GSS were used to predict therapy
      success as defined by the EuResist standard datum definition. Statistical
      significance was assessed using a Wilcoxon signed-rank test. RESULTS: A
      comparison of the therapy-success prediction performances among the different
      interpretation systems for test set A can be found in Table 1, while those for
      test set B are found in Figure 1. Therapy-success prediction of first-line
      therapies with DEnoIAS performed better than DEonlyIAS (p<10-16). CONCLUSIONS:
      Therapy success prediction benefits from the consideration of all available
      mutations. The increase in performance was largest in first-line therapies with
      transmitted drug-resistance mutations.

PMID- 25397489
TI  - Less frequent follow-up in routine care than in trials does not impact resistance
      selection in patients failing DRV/r or ATV/r first line treatment.
AB  - INTRODUCTION: Selection of resistance mutations on antiretroviral therapy (ART)
      including darunavir (DRV/r) or atazanavir (ATV/r) has been reported infrequently
      but mainly in clinical trials where patients were followed very frequently (at
      least four to five clinical visits and viral load measurements per year). The aim
      of this study was to evaluate the rate of resistance at failure and mutational
      patterns emerging in patients receiving DRV/r or ATV/r based-regimen as first
      line treatment and followed in standard clinical practice with less clinical
      visits and viral load measurements (median=2 per year). METHODS: We studied 1,518
      patients starting their first line antiretroviral therapy and followed during at
      least two years (n=799 TVD+DRV/r, n=70 KVX+DRV/r, n=618 TVD+ATV/r, n=31
      KVX+ATV/r). The median viral load at baseline was 76,000 copies/mL and the median
      CD4 cell count 384 cell/mm(3). Virological failure was defined as two consecutive
      viral load=50 copies/mL after previous suppression <50 copies/mL, or failure to
      achieve <50 copies/mL. Predicted susceptibility was determined using the last
      ANRS algorithm. RESULTS: Among the 1,518 patients, 193 (12.7%) failed during the
      two years of follow-up. Among patients failing TVD+DRV/r (n=95), the emerging
      mutations observed were RT M184V (n=8; 8%) and Pro V32I (n=1; 1%). Among patients
      failing KVX+DRV/r (n=8), the emerging mutations observed were RT M184V (n=3; 37%)
      and Pro I47V (n=1; 12%). Among patients failing TVD+ATV/r (n=86), the emerging
      mutations observed were RT M184V (n=9; 10%), Pro N88S (n=2; 2%) and Pro I50L
      (n=1; 1%). Among patients failing KVX+ATV/r (n=4), the emerging mutations
      observed were RT M184V (n=2; 50%) and no Pro mutation. Most of patients retained
      virus predicted to be susceptible to all antiretrovirals (22 virus became
      resistant to 3TC/FTC and three became resistant to ATV). None of them became
      resistant to DRV. CONCLUSIONS: Among 1,518 patients in routine care who started
      their first line treatment with DRV/r or ATV/r, very few of them (1.4%) selected
      resistance mutations at failure with three patients selecting an ATV resistant
      virus. None of them became resistant to DRV. The less frequent follow-up of
      patients in routine care compared to clinical trials does not impact the
      resistance selection rate in patients treated by boosted DRV or ATV based
      regimen.

PMID- 25397490
TI  - Viral escape in the CNS with multidrug-resistant HIV-1.
AB  - INTRODUCTION: HIV-1 viral escape in the cerebrospinal fluid (CSF) despite viral
      suppression in plasma is rare [1,2]. We describe the case of a 50-year-old HIV-1
      infected patient who was diagnosed with HIV-1 in 1995. Antiretroviral therapy
      (ART) was started in 1998 with a CD4 T cell count of 71 cells/iL and HIV-viremia
      of 46,000 copies/mL. ART with zidovudine (AZT), lamivudine (3TC) and efavirenz
      achieved full viral suppression. After the patient had interrupted ART for two
      years, treatment was re-introduced with tenofovir (TDF), emtricitabin (FTC) and
      ritonavir boosted atazanavir (ATVr). This regimen suppressed HIV-1 in plasma for
      nine years and CD4 cells stabilized around 600 cells/iL. Since July 2013, the
      patient complained about severe gait ataxia and decreased concentration.
      MATERIALS AND METHODS: Additionally to a neurological examination, two lumbar
      punctures, a cerebral MRI and a neuropsycological test were performed. HIV-1
      viral load in plasma and in CSF was quantified using Cobas TaqMan HIV-1 version
      2.0 (Cobas Ampliprep, Roche diagnostic, Basel, Switzerland) with a detection
      limit of 20 copies/mL. Drug resistance mutations in HIV-1 reverse transcriptase
      and protease were evaluated using bulk sequencing. RESULTS: The CSF in January
      2014 showed a pleocytosis with 75 cells/iL (100% mononuclear) and 1,184 HIV-1 RNA
      copies/mL, while HIV-1 in plasma was below 20 copies/mL. The resistance testing
      of the CSF-HIV-1 RNA showed two NRTI resistance-associated mutations (M184V and
      K65R) and one NNRTI resistance-associated mutation (K103N). The cerebral MRI
      showed increased signal on T2-weighted images in the subcortical and
      periventricular white matter, in the basal ganglia and thalamus. Four months
      after ART intensification with AZT, 3TC, boosted darunavir and raltegravir, the
      pleocytosis in CSF cell count normalized to 1 cell/iL and HIV viral load was
      suppressed. The neurological symptoms improved; however, equilibrium disturbances
      and impaired memory persisted. The neuro-psychological evaluation confirmed
      neurocognitive impairments in executive functions, attention, working and
      nonverbal memory, speed of information processing, visuospatial abilities and
      motor skills. CONCLUSIONS: HIV-1 infected patients with neurological complaints
      prompt further investigations of the CSF including measurement of HIV viral load
      and genotypic resistance testing since isolated replication of HIV with drug
      resistant variants can rarely occur despite viral suppression in plasma.
      Optimizing ART by using drugs with improved CNS penetration may achieve viral
      suppression in CSF with improvement of neurological symptoms.

PMID- 25397491
TI  - Characterization of natural polymorphic sites of the HIV-1 integrase before the
      introduction of HIV-1 integrase inhibitors in Germany.
AB  - INTRODUCTION: The aim of our study was to analyze the occurrence and evolution of
      HIV-1 integrase polymorphisms during the HIV-1 epidemic in Germany prior to the
      introduction of the first integrase inhibitor raltegravir in 2007. MATERIALS AND
      METHODS: Plasma samples from drug-naive HIV-1 infected individuals newly
      diagnosed between 1986 and 2006 were used to determine PCR-based population
      sequences of the HIV-1 integrase (amino acids 1-278). The HIV-1 subtype was
      determined using the REGA HIV-1 subtyping tool. We calculated the frequency of
      amino acids at each position of the HIV-1 integrase in 337 subtype B strains for
      the time periods 1986-1989, 1991-1994, 1995-1998, 1999-2002, and 2003-2006.
      Positions were defined as polymorphic if amino acid variation was >1% in any
      period. Logistic regression was used to identify trends in amino acid variation
      over time. Resistance-associated mutations were identified according to the IAS
      2013 list and the HIVdb, ANRS and GRADE algorithms. RESULTS: Overall, 56.8%
      (158/278) amino acid positions were polymorphic and 15.8% (25/158) of these
      positions exhibited a significant trend in amino acid variation over time.
      Proportionately, most polymorphic positions (63.3%, 31/49) were detected in the N
      terminal zinc finger domain of the HIV-1 integrase. Motifs and residues essential
      for HIV-1 integrase activity were little polymorphic, but within the minimal non
      specific DNA binding region I220-D270 up to 18.1% amino acid variation was
      noticed, including four positions with significant amino acid variation over time
      (S230, D232, D256, A265). No major resistance mutations were identified, and
      minor resistance mutations were rarely observed without trend over time. E157Q
      considered by HIVdb, ANRS, and GRADE algorithms was the most frequent resistance
      associated polymorphism with an overall prevalence of 2.4%. CONCLUSIONS: Detailed
      knowledge of the evolutionary variation of HIV-1 integrase polymorphisms is
      important to understand the development of resistance in the presence of the
      drug. Our results will contribute to define the relevance of integrase
      polymorphisms in HIV-strains resistant to integrase inhibitors and to improve
      resistance interpretation algorithms.

PMID- 25397492
TI  - Transmitted antiretroviral drug resistance in treatment naive HIV-infected
      persons in London in 2011 to 2013.
AB  - INTRODUCTION: Previously published UK data on HIV transmitted drug resistance
      (TDR) shows that it ranges between 3 and 9.4% [1,2]. However, there are no recent
      data from populations where HIV transmission rates are increasing. The aim of
      this study was to assess the prevalence of TDR in untreated HIV-infected
      individuals attending three HIV specialist clinics under the HIV Directorate,
      Chelsea and Westminster Hospital and based throughout London - the Kobler Clinic,
      56 Dean Street and West London Centre for Sexual Health. METHODS: We included all
      patients with a HIV diagnosis, no history of antiretroviral therapy (ART) intake,
      attending one of the three clinics (Kobler (K), 56 Dean Street (DS) and West
      London (WL)), between 2011 and 2013 who started antiretrovirals. Reverse
      transcriptase (RT) and protease region sequencing was performed using Vircotype
      virtual phenotype resistance analysis. Drug resistance mutations were identified
      according to Stanford University HIV Drug Resistance Database
      (http://hivdb.stanford.edu/). RESULTS: Among 1705 HIV-1-infected patients
      enrolled in the study, 1252 were males (919 were MSM), 107 were females and 346
      had no gender recorded. Ethnicity was 51.1% white British/Irish/other, 6.1%
      African, 2.1% Caribbean, 2.8% Asian, 1.3% Indian/Pakistani/Bangladeshi, 4.2%,
      other, 3.2% not stated, and 29.2% unknown. 547 were from K (84.3% males, 48.3%
      MSM), 826 were from DS (84.3% males, 71.9% MSM), and 109 from WL (87.2% males,
      56.0% MSM), 223 from other sites not specified. 77.5% (1321 of 1705) of patients
      had baseline viral resistance testing performed. Prevalence of primary resistance
      in those with a baseline viral resistance test was 13.5% overall: 19.3% in K,
      14.9% in DS, and 14.7% in WL. The most common mutations detected were: NRTI:
      184V, 215F, 41L; NNRTI 103N, 179D, 90I; PI 90M, 46I, and 82A. Among patients who
      tested with TDR, 79.1% had one single mutation, 18.7% and 2.2% exhibited dual or
      triple class-resistant viruses, respectively. CONCLUSIONS: This study across a
      large HIV Medicine Directorate reported an overall TDR prevalence which is higher
      than that previously published and with significant rates of NNRTI resistance at
      baseline.

PMID- 25397493
TI  - Use of deep sequencing data for routine analysis of HIV resistance in newly
      diagnosed patients.
AB  - INTRODUCTION: Use of deep sequencing is becoming a critical tool in clinical
      virology, with an important impact in the HIV field for routine diagnostic
      purposes. Here, we present the comparison of deep and Sanger sequencing in newly
      diagnosed HIV patients, and the use of DeepChek v1.3 & VisibleChek for their
      interpretation and integration with virological and clinical data. PATIENTS AND
      METHODS: Plasma samples from 88 newly diagnosed HIV-1-infected patients were
      included in the study. Median age (IQR) was 37 (27-47), median CD4 count (IQR)
      was 387 (220-554), and 85% were males. Median Viral Load (Log, IQR) was 5.03
      (4.51-5.53). Deep sequencing was obtained using a GS-Junior (Roche). Sequences
      were preprocessed with the 454 AVA software; aligned reads were uploaded into the
      DeepChek v1.3 system (ABL SA). Sanger sequences (Trugene), were uploaded in
      parallel. Stanford algorithm (version 7.0) resistance interpretation to first
      line drugs and all the mutations (score>=5) were analyzed. For deep sequencing,
      1%, 5% and 10% thresholds were chosen for resistance interpretation. RESULTS:
      Using VisibleChek for analysis, we were able to describe the detection of any
      mutation using Sanger in 37/88 patients, with a total number of 50 Stanford >=5
      mutations, K103N and E138A being the most prevalent (n=4). Using UDS-1%, we found
      72/88 patients with at least one mutation (total of 206 Stanford >=5 mutations).
      Using Sanger data, 9/88 patients (10.22%) showed any resistance to NNRTIs, while
      none showed resistance to NRTIs or PIs. Using UDS-10% increased resistance to
      NRTIs [3/88 (3.40%)], to NNRTIs 12/88 (13.63%), and to a lesser extent to PIs
      [1/88 (1.13%)]. Using UDS-5% increased resistance to NRTIs [4/88 (4.54%)] and to
      NNRTIs [12/88 (13.63%)], but not to PIs. Using UDS-1% increased resistance to all
      classes: NRTIs [14/88 (15.90%)], NNRTIs [26/88 (30.68%)], and PIs [6/88 (6.81].
      CONCLUSIONS: DeepChek and VisibleChek allow for an easy, reliable and rapid
      analysis of UDS data from HIV-1. Compared to Sanger data, UDS detected a higher
      number of resistance mutations. UDS with a 5 &10% threshold resulted in an
      increase in the number of patients with any degree of resistance mainly to NRTI,
      NNRTIs. Going down as low as 1% increased resistance to all classes. A correct
      definition of clinically relevant thresholds for the interpretation of minor
      variant detection for different classes of ARVs is needed.

PMID- 25397494
TI  - New dolutegravir resistance pattern identified in a patient failing
      antiretroviral therapy.
AB  - INTRODUCTION: The most recently approved antiretroviral, the integrase inhibitor
      dolutegravir (DTG), is described to be a very potent drug with a unique
      resistance profile, but a certain degree of cross-resistance to RAL or EVG
      induced drug resistance, which is mediated mainly by integrase mutations at
      positions 140 and 148. The impact of a single N155H mutation to DTG resistance is
      described to be minor. However, there is only rare data available about the
      impact of N155H in the context of secondary site integrase mutations. Here, we
      present a case of virological failure in a DTG treated patient based on N155H
      mutation background. METHODS: Therapy monitoring of an HIV-HCV co-infected
      patient harbouring already an omni-drug-class resistant HIV-1 in consequence of
      more than 20 years ART history. Drug susceptibility testing was performed by RT
      PCR from plasma and subsequent Sanger sequencing. Tropism testing was done from
      proviral DNA with FPR cut-offs according to the German recommendations. RESULTS:
      In 2013, the patient harbouring a virus with high level resistance to all RTI and
      PI received a regimen containing FTC, TDF, DRV/r, RPV, T20, and RAL to handle a
      viral load of 5000 RNA copies/mL, but never achieved fully suppressed viral load.
      In June 2013, after S119R, N155H and E157Q mutations in viral integrase were
      detected, the patient received DTG, and RAL was stopped. One month later, when
      viral load was undetectable for the first time since 2007, ART was de-escalated
      by removing T20. Since February 2014, low-level viral load was re-detectable. Two
      new mutations T97A and S147G in the integrase and no other new resistance
      associated mutations in protease and reverse transcriptase in comparison to the
      sample analyzed in June 2013 were detected. CONCLUSIONS: Highly resistant HIV-1
      strains have been a common problem in the past. Their frequencies were pushed
      back by highly potent ART, but the virus is still able to become resistant
      against all available antiretrovirals at once. The here documented strain became
      resistant to DTG without carrying mutations at the described positions 140 and
      148, but in the context of integrase N155H. Since N155H alone is described not to
      contribute sufficient resistance to DTG, there seems to be a need to re-check
      viruses with N155H plus minor mutations (like T97A, S119R, S147G and E157Q)
      potentially contributing to DTG resistance.

PMID- 25397495
TI  - Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1
      positive patients in Turkey.
AB  - INTRODUCTION: The objective of this study was to determine the transmitted drug
      resistance mutations (TDRMs) in newly diagnosed HIV-1 positive patients in
      Turkey. MATERIALS AND METHODS: The study was carried out between 2009 and 2014
      and antiretroviral naive 774 HIV-1 infected patients from 19 Infectious Diseases
      and Clinical Microbiology Departments in Turkey were included; gender: 664 (86%)
      male, median age: 37 (range; 1-77), median CD4+T-cell: 360 (range; 1-1320)
      count/mm(3), median HIV-RNA load: 2.10+E6 (range; 4.2+E2-7.41+E8) IU/mL. HIV-1
      drug resistance mutations were detected by population based sequencing of the
      reverse transcriptase (codon 41-238) and protease (codon 1-99) domains of pol
      gene of HIV-1, and analyzed according to the criteria by the World Health
      Organization 2009 list of surveillance drug resistance mutations [1]. RESULTS:
      The patients had TDRMs to NRTIs (K65R, M184V), NNRTIs (K101E, K103N/S, G190A/E/S,
      Y181I/C, Y188H/L) and PIs (M46L, I54V, L76V, V82L/T, N83D, I84V, L90M). The
      prevalence of overall TDRMs was 6.7% (52/774). Resistance mutations were found to
      be 0.7% (6/774), 4.1% (32/774) and 2.1% (17/774) to NRTIs, NNRTIs and PIs drug
      groups, respectively. Three patients had NRTIs+NNRTs resistance mutations
      (M184V+K103N) as multi-class drug resistance. However, thymidine analogue
      resistance mutations (TAMs) determined two distinct genotypic profiles in the HIV
      1 reverse transcriptase: TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R,
      K219E/Q, and T215F. The prevalence of TAM1 and TAM2 were 7.7% (60/774) and 4.3%
      (34/774), respectively. CONCLUSIONS: The TDRMs prevalence of antiretroviral naive
      HIV-1 infected patients may be suggested current situation of Turkey. These long
      term and large-scale results show that the resistance testing must be an integral
      part of the management of HIV infection in Turkey.

PMID- 25397496
TI  - Comparison of HIV-1 drug resistance profiles generated from novel software
      applications for routine patient care.
AB  - INTRODUCTION: Clinical laboratories performing routine HIV-1 genotyping antiviral
      drug resistance (DR) testing need reliable and up-to-date information systems to
      provide accurate and timely test results to optimize antiretroviral treatment in
      HIV-1-infected patients. MATERIALS AND METHODS: Three software applications were
      used to compare DR profiles generated from the analysis of HIV-1 protease (PR)
      and reverse transcriptase (RT) gene sequences obtained by Sanger sequencing assay
      in 100 selected clinical plasma samples from March 2013 through May 2014.
      Interpretative results obtained from the Trugene HIV-1 Genotyping assay (TG;
      Guidelines v17.0) were compared with a newly FDA-registered data processing
      module (DPM v1.0) and the research-use-only ViroScore-HIV (VS) software, both of
      which use the latest versions of Stanford HIVdb (SD v7.0) and geno2pheno (G2P
      v3.3) interpretive algorithms (IA). Differences among the DR interpretive
      algorithms were compared according to drug class (NRTI, NNRTI, PI) and each drug.
      HIV-1 tropism and integrase inhibitor resistance were not evaluated (not
      available in TG). RESULTS: Overall, only 17 of the 100 TG sequences obtained
      yielded equivalent DR profiles among all 3 software applications for every IA and
      for all drug classes. DPM and VS generated equivalent results with >99.9%
      agreement. Excluding AZT, DDI, D4T and rilpivirine (not available in G2P), ranges
      of agreement in DR profiles among the three IA (using the DPM) are shown in Table
      1. CONCLUSIONS: Substantial discrepancies (<75% agreement) exist among the three
      interpretive algorithms for ETR, while G2P differed from TG and SD for resistance
      to TDF and TPV/r. Use of more than one DR interpretive algorithm using well
      validated software applications, such as DPM v1.0 and VS, would enable clinical
      laboratories to provide clinically useful and accurate DR results for patient
      care needs.

PMID- 25397497
TI  - Analysis of transmitted HIV-1 drug resistance using 454 ultra-deep-sequencing and
      the DeepChek((r))-HIV system.
AB  - INTRODUCTION: Next-generation sequencing (NGS) is capable of detecting resistance
      associated mutations (RAMs) present at frequencies of 1% or below. Several
      studies have found that baseline low-frequency RAMs are associated with failure
      to first-line HAART. One major limitation to the expansion of this technology in
      routine diagnostics is the complexity and laboriousness integral to
      bioinformatics analysis. DeepChek (ABL, TherapyEdge) is a CE-marked software that
      allows automated analysis and resistance interpretation of NGS data. OBJECTIVE:
      To evaluate the use of 454 ultra-deep-sequencing (Roche((r)) 454, Life Sciences;
      454-UDS) and DeepChek for routine baseline resistance testing in a clinical
      diagnostic laboratory. METHODS: 107 newly diagnosed HIV-1-infected patients
      (subtypes: A, n=9; B, n=52; C, n=21; D, n=2; F, n=3; G, n=1; CRF01, n=7; CRF02,
      n=7; CRF06, n=1; CRF07, n=1; CRF10, n=1 and unassigned complex, n=2) with a
      median plasma viral load of 88,727 copies/mL (range: 1380-2,143,543) were tested
      by 454-UDS and Sanger sequencing for the detection of protease and reverse
      transcriptase RAMs. In addition, integrase RAMs were investigated in 57 of them.
      Sequence analysis and resistance interpretation were performed using DeepChek
      applying 1% and 20% thresholds for variant detections; filters applied were
      comparison between Sanger and 454-UDS, and Stanford and IAS list for resistance
      interpretation. RESULTS: The time elapsed from generation of raw 454 data
      (between 2,000-5,000 sequences/sample) to elaboration of a resistance report was
      approximately 10 minutes per sample, equivalent to the time required for the same
      process using Sanger sequencing. Four patients (3.7%) showed baseline resistance
      by Sanger and 454-UDS at frequencies above 20%, which affected both NRTIs (n=2)
      and NNRTIs (n=2). In addition, 12 patients (11.2%) showed transmitted drug
      resistance (TDR) by 454-UDS at frequencies below 20% affecting NRTIs (n=9),
      NNRTIs (n=7) and PIs (n=2). Integrase resistance was not detected at baseline by
      454-UDS or Sanger sequencing. CONCLUSIONS: DeepChek allowed easy and rapid
      analysis and interpretation of NGS data, thus facilitating the incorporation of
      this technology in routine diagnostics. The use of NGS considerably increased the
      detection rates of TDR to NRTI, NNRTIs and PIs. No transmitted resistance to
      integrase inhibitors was found in our population by Sanger sequencing or UDS.

PMID- 25397498
TI  - Time trends in HIV-1 transmitted drug resistance mutation frequency in Poland.
AB  - INTRODUCTION: In Poland, the HIV epidemic has shifted recently from being
      predominantly related to injection drug use (IDU) to being driven by
      transmissions among men-who-have-sex-with-men (MSM). The number of new HIV cases
      has increased in the recent years, while no current data on the transmitted drug
      resistance associated mutations (tDRM) frequency trend over time are available
      from 2010. In this study, we analyze the temporal trends in the spread of tDRM
      from 2008 to 2013. MATERIALS AND METHODS: Partial pol sequences from 833
      antiretroviral treatment-naive individuals of European descent (Polish origin)
      linked to care in 9 of 17 Polish HIV treatment centres were analyzed. Drug
      resistance interpretation was performed according to WHO surveillance
      recommendations, subtyping with REGA genotyping 2.0 tool. Time trends were
      examined for the frequency of t-DRM across subtypes and transmission groups using
      logistic regression (R statistical platform, v. 3.1.0). RESULTS: Frequency of
      tDRM proved stable over time, with mutation frequency change from 11.3% in 2008
      to 8.3% in 2013 [OR: 0.91 (95% CI 0.80-1,05), p=0.202] (Figure 1a). Also, no
      significant differences over time were noted for the subtype B (decrease from
      8.4% 2008 to 6.2% in 2013 [OR: 0.94 (95% CI 0.79-1.11), p=0.45] and across non-B
      variants [change from 22.6% 2008 to 23.1% in 2013, OR: 0.94 (95% CI 0.75-1.19),
      p=0.62]. When patient groups were stratified according to transmission route, in
      MSM there was a trend for a NNRTI t-DRM decrease (from 6.8% 2008 to 1% in 2013,
      OR: 0.61 (95% CI 0.34-1.02), p=0.0655, slope -0.74%/year) (Figure 1b), related to
      the subtype B infected MSM (decrease from 7% 2008 to 1% in 2013, OR: 0.61 (95% CI
      0.34-1.03), p=0.0662, slope -0.75%/year). Overall tDRM frequency decrease was
      also noted for the heterosexually infected patients [from 17.6% 2008 to 10.3% in
      2013, OR: 0.83 (95% CI 0.67-1.02, p=0.077, slope -2.041%/year)] but did not
      associate with drug class (Figure 1c). In IDUs, the trends in t-DRM frequency
      were not significant over time (change from 1.9% in 2008 to 0 in 2013 [OR:1.24
      (95% CI 0.73-2.26), p=0.4)]. CONCLUSIONS: The frequency of t-DRM in Poland is
      generally stable over time. Decrease in the overall tDRM frequency in
      heterosexual infected cases and NNRTI resistance in subtype B infected MSM may be
      related to the higher treatment efficacy of current cART.

PMID- 25397499
TI  - High frequency of antiviral drug resistance and non-b subtypes in HIV-1 patients
      failing antiviral therapy in Cuba.
AB  - INTRODUCTION: Emergence of HIV-1 drug resistance may limit the sustained benefits
      of antiretroviral therapy (ART) in settings with limited laboratory monitoring
      and drug options. The objective is to implement the surveillance of drug
      resistance and subtypes in HIV-1 patients failing ART in Cuba. METHODS: This
      study compiled clinical and genotypic drug resistance data 588 ART-experienced
      HIV-1 patients attending a clinical center in Havana in 2009-2013. Drug
      resistance testing was performed as part of routine clinical care. Drug
      resistance mutations and levels were determined using Rega version 8.0.2.
      RESULTS: Eighty-three percent received solely ART containing at least three
      drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years)
      and exposed to more ART regimens (median: 4 vs 2 regimens) compared to patients
      from 2011-2013. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside
      RTI (NNRTI) and PI mutations were present in 83.5, 77.4 and 52.0%. Full-class
      resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected
      in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in
      12.8, 28.7, 0 and 0% after first-line failure (164 patients) and in 23.1, 34.6,
      3.8 and 3.1% after second-line failure (130 patients). Subtype B (32.5%), BG
      recombinants (19.6%) and CRF19_cpx (16.2%) were the most prevalent genetic forms.
      Subtype distribution did not change significantly between 2009-2010 and 2011
      2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002).
      CONCLUSIONS: Our study found a high prevalence of drug resistance and supports
      the need for appropriate laboratory monitoring in clinical practice and access to
      drug options in case of virological failure.

PMID- 25397500
TI  - Use of dolutegravir in two INI-experienced patients with multiclass resistance
      resulted in excellent virological and immunological responses.
AB  - INTRODUCTION: Dolutegravir is a second generation integrase inhibitor with a
      proposed high genetic barrier to resistance. However, in clinical trials,
      decreased virological response was seen in a subset of patients with prior
      exposure to raltegravir and multiple integrase resistance mutations. METHODS: We
      describe two cases of HIV subtype B-infected patients starting dolutegravir after
      previous failure on a raltegravir-containing regimen with extensive resistance.
      Genotypic analysis was performed using population sequencing and 454 ultradeep
      sequencing of integrase at time of raltegravir exposure. RESULTS: Both patients
      were diagnosed in early 1990s and received mono- and dual therapy, followed by
      several cART-regimens. Due to presence of extensive resistance, the genotypic
      susceptibility score of these regimens never reached a score >2 and never
      resulted in sustained virological suppression despite good adherence. Early 2012,
      the clinical condition of patient 1 worsened during persistent failure of a mega
      cART regimen despite excellent drug levels. Six major PI, six minor PI, seven
      NRTI, six NNRTI and two INI mutations plus DM-virus were detected (Table 1).
      Ultra-deep sequencing of integrase showed the selection of Q148R, E138K+Q148K,
      and N155H variants and phenotypic raltegravir resistance was demonstrated. After
      addition of dolutegravir and enfuvirtide to the failing regimen (zidovudine,
      lamivudine, tenofovir, etravirine, darunavir/ritonavir, maraviroc), viral load
      (VL) decreased from 244,000 to <20 cps/mL within five months, CD4-count increased
      (33 to 272 mm(3)) and the clinical condition improved substantially. In patient
      2, similar worsening of the clinical condition was observed late 2012 during
      persistent failure on mega-cART. Five major PI, six minor PI, nine NRTI, seven
      NNRTI and one INI mutation plus DM-virus were detected. Ultra-deep sequencing
      showed selection of N155H, followed by Q95K and V151I variants and phenotypic
      raltegravir resistance was demonstrated. Dolutegravir was added to his failing
      regimen (zidovudine, lamivudine, etravirine, atazanavir/ritonavir, maraviroc) at
      a VL of 39,000 cps/mL. Sustained virological suppression was reached within five
      months with considerable increase of CD4-count (41 to 175 mm(3)) and slight
      improvement of clinical condition. CONCLUSIONS: We present the first patients
      with extensive integrase resistance who were treated with dolutegravir in
      clinical practice and who achieved excellent virological and immunological
      success. These cases demonstrate the high genetic barrier of dolutegravir.

PMID- 25397501
TI  - Resistance remains a problem in treatment failure.
AB  - INTRODUCTION: Proven resistance against HIV drugs, either by phenotyping or
      genotyping is a rare event in clinical trials. The overall assumption of drug
      resistance disappearing is additionally driven by the recommendations to screen
      for transmitted drug resistance, leading to large numbers of examinations with
      relatively low rates of resistance. Goal of our analysis was to assess if drug
      resistance in treatment failure is also decreasing outside of clinical trials.
      MATERIALS AND METHODS: The MIB database at timepoint of analysis consists of data
      from 2876 HIV infected patients. Besides various laboratory parameters, clinical
      data and treatment history is included. HIV-1 protease and reverse transcriptase
      sequences were analyzed using the HIV-GRADE drug resistance algorithm. As in only
      a small number of patients genotypic resistance testing for integrase inhibitors
      was performed, mainly due to reimbursement reasons, it was assumed that failing
      treatment on a previous integrase inhibitor containing regimen is equate to
      resistance. RESULTS: Of the 2876 patients in the database, 220 had a treatment
      change due to treatment failure between 2009 and 2012, a genotypic resistance
      testing at an appropriate timepoint of maximum four weeks before treatment change
      and a treatment duration of at least six months before treatment failure. In
      2009, 61% of patients showed no drug resistance while 39% showed resistance
      against one or more drug classes (two or more drug classes: 19.5%; three or more
      drug classes: 2.4%, four drug classes 2.4%). In 2012, no resistance was found in
      52% of patients while resistance against three or more drug classes was found in
      nearly 14% of patients (one or more: 48%; two or more 23%; four classes: 4.5%).
      CONCLUSIONS: Treatment failure with viral load sufficiently high for drug
      resistance testing was not frequently observed in our database. Nevertheless,
      treatment failure was often associated with drug resistance against at least one
      drug class. With more use of the newer drug classes, resistance against those new
      classes will become more common and rates of multiclass resistance will be
      increasing.

PMID- 25397502
TI  - Time to virologic failure for patients taking their first antiretroviral regimen
      and the subsequent resistance profiles.
AB  - INTRODUCTION: The resistance profiles of first-line antiretroviral therapy (ART)
      regimens after virologic failure have yet to be studied in a clinic setting in
      the modern treatment era. Time to virologic failure among three standard first
      line regimens and the resistance profiles of these failures were compared.
      MATERIALS AND METHODS: All HIV-positive persons aged 16 and over starting a three
      drug first-line ART regimen were retrospectively identified at a Toronto
      community clinic (1 January 2006-1 January 2013). The regimens included a
      backbone of two NRTIs and a third agent; a PI, an NNRTI, or an II. Patients must
      have been on treatment for at least 14 days and have at least one VL test within
      6 months after starting treatment. The primary outcome was virologic failure
      defined as either: no suppression by 6 months, or after suppression, two
      consecutive, detectable VL200 copies/mL at least 14 days apart or one VL>200
      copies/mL. Time to failure was compared using a proportional hazards model
      adjusting for demographic and clinical factors. Resistance profiles of NRTIs and
      third agents are described in patients with virologic failure who had both
      baseline and virologic failure genotypes. RESULTS: Six hundred sixty patients
      (93% male) were included with a mean age of 38.9 and a median follow-up period of
      35.3 (32.2-39.3) months. Distribution of third agent use was: PI 37.3% (n=246),
      NNRTI 55.9% (n=369) and II 6.8% (n=45). Virologic failures occurred in 81/246
      (33%) with PI, 87/369 (24%) with NNRTI and 11/45 (24%) with II. Compare to PIs,
      time to failure was longer with NNRTIs (p=0.0013) and similar for IIs (p=0.1562).
      No evidence that failure with NNRTIs was different from IIs (p=0.9139). Of the
      660 patients, 567 (86%) had a baseline genotype. Of the 567 patients, 179 had
      virological failure. Of the 179, 145(81%) had a baseline genotype and only 37
      (21%) had both a baseline and follow-up genotype. Upon failure, emerging ART
      resistance was rare. No new PI or II mutations were identified and one new NNRTI
      (Y181C) mutation was identified. Three patients taking PI-based regimens
      developed NRTI mutations (M184V, M184I, T215Y). CONCLUSIONS: Time to virologic
      failure was significantly greater in the NNRTI group compared to the PI group. If
      failure did occur, ART resistance rarely developed with no PI mutations but a few
      NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those
      taking NNRTI-based regimen.

PMID- 25397503
TI  - Seroincidence of HIV and prevalence of transmitted drug resistance of HIV-1
      strains among persons seeking voluntary counselling and testing in Taiwan.
AB  - INTRODUCTION: The total case number of persons who are newly diagnosed with HIV
      continues to increase in Taiwan and men who have sex with men (MSM) have re
      emerged as the leading risk group for HIV transmission. In this study, we aimed
      to estimate the incidence rate of HIV infection among those individuals who
      sought voluntary counselling and testing (VCT) service at a university hospital.
      METHODS: Between 1 April, 2006 and 31 December, 2013, 18,246 tests for HIV
      antibody were performed among 12143 individuals at the VCT service. A total of
      2157 individuals who tested negative for anti-HIV antibody had subsequent follow
      up tests at the same VCT service, which composed the study population for
      estimation of incidence rate of recent HIV infection. The BED assays were used to
      identify recent HIV infections that occurred within the previous six months
      before seeking VCT service. RESULTS: During the 6.5-year study period, 647
      individuals were diagnosed as being HIV-positive, with an overall HIV
      seroprevalence of 3.55% (95% CI 3.27-3.82). The overall incidence rate of HIV
      infection was estimated 4.13 per 100 person-years of follow-up (95% CI 3.67-4.69
      per 100 person-years of follow-up). MSM had an estimated 10-fold higher
      seroprevalence and seroincidence of HIV than heterosexuals. Of 647 clients
      testing positive for HIV, 603 clients were MSM (93.2%) and 477 patients (70.8%)
      subsequently sought HIV care at the hospital; 226 (47.4%) were diagnosed as
      having recent HIV infections by the BED assay, while 244 (51.2%) long-term
      infection and 7 without data by the BED assay. Of those patients, 173 (75.6%) and
      178 patients (73.0%) with recent HIV infection and long-term infection had data
      of transmitted drug resistance mutations, respectively. The prevalence of
      transmitted drug resistance mutations to any class of antiretroviral therapy was
      9.0% and 10.6% (p=0.68), respectively, of the HIV-1 strains from the patients
      with recent HIV infection and long-term infection, respectively. CONCLUSIONS: The
      seroincidence rate of HIV among persons seeking VCT was estimated 4.13 per 100
      person-years of follow-up. The prevalence of transmitted drug resistance to any
      class of antiretroviral agents was similar between those who were recently
      infected with HIV and those who had long-term infection in Taiwan.

PMID- 25397504
TI  - Early clinical response and presence of viral resistant minority variants: a
      proof of concept study.
AB  - INTRODUCTION: Traditional genotyping assays detect viral variants present in at
      least 15-25% of the entire virus population. We tested the Next generation GS
      Junior System (NGS) setted with a detection limit of 0.05% and evaluated the
      clinical relevance of low prevalent mutations. METHODS: NGS was performed on the
      plasma of 26 infected individuals who started a TDF/FTC/RPV (15 subjects) or
      TDF/FTC/EFV (11 subjects) cART after a routine HIV-1 drug-resistance negative
      test by Viroseq HIV-1 Genotyping System. Amplicon Sequencing of HIV-1 RT and PR
      Plate (Roche) was performed following the manufacturer's instructions. HIV-1
      variants were analyzed by a specific HIV-1 tool by AVA software v. 2.7. The
      updated IAS resistance mutations list (March 2013) was considered for the
      analysis of resistance positions. Patients were followed testing viral load and
      immunologic parameters. RESULTS: Twenty four males and two females with a mean
      age of 43 years were included. Twenty-one were nave for cART. At baseline, median
      HIV-RNA was 4.57 log copies/mL (range 2.15-6.57) and CD4 count 315 cells/mcL
      (range 16-648). In 18 patients, NGS did not detect any additional variant
      relevant for the selected cART compared to population genotyping. In the
      remaining eight patients resistance conferring mutations to part of the ongoing
      regimen were detected. Single mutations E138K (two cases) and M184V in three
      distinct patients and V90I+G190E; M184V+A98S; Y215F+V118I+T215I;
      L210S+T215I+F227L; and A62V+D67G+K70N+188H in the remaining five subjects. In all
      cases, the mutation prevalence was inferior to 5%. The mean daily reduction of VL
      was -3759 copies/mL in patients without NGS detected mutations and -1045
      copies/mL in those with mutations. The median KM estimates for reaching an HIV
      RNA blood level <50 copies/mL were 127 days and 161 days, respectively. One
      patient without baseline resistance selected for M184I+E138K+T215I (NGS) after
      four months of TDF/FTC/RPV therapy. CONCLUSIONS: NGS detected low-frequency HIV-1
      variants harbouring RT drug resistance mutations that could have affected the
      therapy outcome. However, viral decay in an early cART phase was not affected by
      the presence of resistant minority variants. The low prevalence of the detected
      mutation, the limited effect on the combination regimen and the potency of cART
      components could be possible explanations of our findings. Longer follow-up and
      larger casuistries are needed to determine the clinical relevance of NGS in
      routine clinical practice and eventually define a clinically relevant mutations'
      prevalence.

PMID- 25397505
TI  - Resistance mutations in protease gene at baseline are not related to virological
      failure in patients treated with darunavir/ritonavir monotherapy.
AB  - INTRODUCTION: Monotherapy with darunavir plus ritonavir (DRV/r) is a good
      maintenance strategy for suppressed HIV-infected patients. The clinical trials
      designed to prove the efficacy of PI/r do not include patients with resistance
      mutation in protease gene [1,2]. Sometimes in routine practice, basically to
      avoid NRTIs toxicity, monotherapy with DRV/r is used despite PI resistance
      mutations. The aim of this study is to know the effect of previous protease
      resistance mutation on DRV/r monotherapy efficacy. MATERIALS AND METHODS: We
      designed an observational cohort study of adults in treatment with DRV/r
      monotherapy in a tertiary Spanish hospital since 2011 to 2014. Demographic data
      and clinical outcomes were described. The analysis of efficacy was done according
      to the snapshot algorithm (defining virological failure as viral load >50
      copies/mL, ITTe, at 48 and 96 weeks). We analyzed the difference of efficacy
      between patients with and without baseline resistance mutations at 48 and 96
      weeks by using the chi(2) test; and during the follow-up by using the Kaplan
      Meier test. The statistical analysis was done with SPSS 17.0. RESULTS: Eighty
      nine patients were included in the cohort but 14 were excluded because they had
      not reached more than six months with monotherapy. The cohort was composed mainly
      by men (78%), the medium age was 51 years (SD+/-10), 35% were MSM and 19% were
      former IDU. Twenty-four patients (35%) had a previous diagnosis of AIDS. The mean
      time taking NRTIs was 10.5 years (SD+/-5.4). Sixty-four patients (85%) had been
      treated with PI in the past. Previous failure with PI had been reported in 15
      (20%). A resistance mutation test had been done at baseline in 45 patients (51%).
      Twenty-two patients (29%) had some mutations in protease gene, 10 patients (13%)
      had major mutations and 1 patient had some mutations of resistance for darunavir
      (I64V). At 48 weeks, 93% (CI 95% 86-98%) had VL<50 copies/mL, and 79% (CI 95% 67
      89%) at 96 weeks. There were not differences between patients with or without
      resistance mutations (p=0.53). After a median follow-up of 70 weeks, 88% of
      patients remain free of virological failure and there were not differences
      between both groups. CONCLUSIONS: According to these data, previous resistance
      mutations in the protease gene, which do not affect darunavir, are not related
      with the efficacy in patients treated with DRV/r monotherapy.

PMID- 25397506
TI  - Primary drug resistance at diagnosis of HIV-1 infection: a Portuguese cohort.
AB  - INTRODUCTION: Presence of viral mutations conferring resistance to antiretroviral
      drugs has potential impact on success of antiretroviral therapy (ART). The aim of
      this study was to describe the prevalence of resistance-associated mutations in
      HIV-infected patients without prior ART in a Portuguese cohort. MATERIALS AND
      METHODS: Retrospective single-centre study of patients newly diagnosed with HIV-1
      infection between 2006 and 2012. Resistance genotyping was obtained with HIV
      TRUGENE((r)) and Viroseq((r)) tests and the analysis of drug resistance was based
      on the Stanford University HIV Drug Resistance Database. Epidemiological data was
      also gathered. Continuous variables were summarized by mean and standard
      deviation, whereas categorical variables were presented as proportions.
      Comparison of proportions was performed with Chi square and Fisher exact test
      while means were compared with Student test. Statistical significance was assumed
      when p<0.05. Statistical analysis was performed with SPSS 21.0((r)). RESULTS:
      Resistance testing was performed in 624 patients. General characteristics of the
      patients are summarized in Table 1. Mutations were found in 291 (46.6%) patients
      but resistance-associated mutations were present in 79 (12.7%) patients.
      Resistances to different drug classes were the following: NNRTIs-resistance in 42
      (6.7%) patients; NRTIs-resistance in 19 (3.0%) patients; PIs-resistance in 30
      (4.8%) patients. Only 10 (1.6%) patients presented simultaneous resistance
      associated mutations to more than one class of drugs. There were no statistical
      significant differences between the years at which HIV-1 was diagnosed. Also no
      significant difference in the distribution of the parameters age, sex, CD4-cell
      count, and viral load, between groups with and without resistance was identified.
      Resistance-associated mutations were significantly more common in patients with
      non-B HIV-1 subtypes (15.4% vs 9.8%; p=0.048) and in those presenting with AIDS
      (18.2% vs 11.1%; p=0.03). CONCLUSIONS: Prevalence of resistance-associated
      mutations identified in this study was similar to those reported in similar
      studies from Western Europe. Knowledge about the epidemiology of primary
      resistance in our country is important in order to improve HIV care.

PMID- 25397507
TI  - Lamivudine monotherapy as a safe option for HIV-infected paediatric clients with
      adherence challenges: new evidence from a large South African cohort.
AB  - INTRODUCTION: HIV-infected children in resource-poor settings comprise a unique
      population who require antiretroviral therapy (ART) in careful consideration of
      social and structural barriers to compliance. Given these aggregate challenges
      and emerging research into "holding" treatment options, we investigated the
      efficacy of lamivudine monotherapy (LM) as an alternative to more complex second
      and third line therapies. METHODS: A retrospective review of all eligible LM
      events (=6 months) from a cohort of two linked health facilities in the Eastern
      Cape Province, South Africa was undertaken. Events were disaggregated according
      to absolute CD4 count at initiation (Group 1: >200 cells/L, n=64; Group
      2:=200cells/L, n=10). Study endpoints were defined as a decline of absolute
      CD4=200 cells/L (Group 1), WHO stage 3 or 4 event (Groups 1& 2), or initiation of
      second or third line (Groups 1 & 2). RESULTS: Seventy-four eligible LM events
      were identified among 71 HIV-positive children (58% male; median age at LM 9.7
      years and median LM duration 11.5 months). CD4 decreases and measured WHO stage 3
      or 4 events did not yield overall significance between groups (Table 1). No
      deaths were recorded. CONCLUSIONS: LM offers a promising alternative approach to
      ART management in young patients with an absolute CD4 >200 cells/L pending
      availability and/or willingness to adhere to second or third line therapies. In
      more immunocompromised children, LM may be considered as a last option if either
      the child or caretaker has concerns about second or third line management, or has
      defaulted repeatedly.

PMID- 25397508
TI  - Potential drug-drug interactions in HIV-perinatally infected adolescents on
      antiretroviral therapy in Buenos Aires, Argentina.
AB  - INTRODUCTION: An increasing number of treatment-experienced perinatally HIV
      infected adolescents (PHA) are being transitioned from paediatric centres to
      adult HIV-care [1]. Most of them had been heavily exposed to antiretroviral drugs
      (ARVs), harbour drug-resistant viruses and require non-antiretroviral medication
      due to comorbidities [2]. This may predispose for clinically significant drug
      drug interactions (CSDDIs) [3]. There are no studies concerning CSDDIs in PHA. We
      aimed to evaluate the prevalence of concomitant medications and CSDDIs in PHA who
      were transitioned for adult HIV-care to the Infectious Diseases Unit, Cosme
      Argerich Hospital, Buenos Aires City, Argentina. MATERIALS AND METHODS:
      Descriptive pilot cross-sectional study (March to June 2014). PHA under ARVs at
      the time of the study were assessed for concomitant medication. CSDDIs were
      screened and categorized using the University of Liverpool Drug Interactions
      Program (www.hiv-druginteractions.org) [4]. RESULTS: Forty-five patients were
      included. Female sex: 53%. Median (IQR) age: 20 years (18-22). CDC-stage C was
      observed in 27 (79%); 50% had >=1 comorbidities including 3 with HCV co
      infection. Drug abuse was observed in 6 (13%). The median of prior ARV regimens
      was 3 (3-5). Current ARV regimen included: PI: 87%, NNRTI: 27%, INSTI: 20%,
      enfuvirtide: 7% and CCR5 inhibitor: 4%. Median CD4 T-cell count: 568 cells/mL
      (279-771). Viral load <50 copies/mL: 80%. Sixty percent (27/45) had >=1 co
      medications (median 1). The most frequent co-medications were NSAIDs (40%),
      hormonal therapy (19%) and antimicrobials (19%). Use of herbal supplements was
      observed in 10 (22%). Overall, 23 (51%) had >= 1 CSDDIs: 19/27 (70%) with co
      medication (orange flag=18 and red flag=1); and 2/10 (20%) with herbal
      supplements. ARV-ARV interactions were observed in 4/45 (9%): unboosted
      atazanavir+tenofovir (n=2), unboosted atazanavir+efavirenz (n=1) and
      lopinavir/ritonavir+efavirenz (n=1) (all orange flag). Considering patients with
      CSDDIs, 6 (26%) had a CSDDI that could reduce ARV levels. CONCLUSIONS: In this
      pilot study, a high prevalence of comorbidities, co-medications and CSDDIs was
      observed in PHA. A considerable proportion of patients had CSDDIs with a
      potential to cause sub-therapeutic ARV levels, what could be a concern in
      patients harbouring drug-resistance viruses. Therefore, clinicians should be
      aware of comorbid conditions pharmacologic management in order to avoid CSDDIs
      with ARVs agents.

PMID- 25397509
TI  - Tolerability is more important than simplicity for treatment durability.
AB  - INTRODUCTION: Many studies have shown the superiority of single tablet regimens
      (STRs) of antiretrovirals for the treatment of HIV in terms of efficacy,
      adherence and rate of hospitalisation as they offer a low pill burden and once
      daily dosing. Our objective was to compare the duration of first-line STRs to
      multi-tablet regimens. METHODS: From our clinical database, we selected patients
      initiating any of the major first-line regimens between 2007 and 2013. Two STRs,
      Atripla (ATP) and Complera (CPLR), were compared to three non-STRs: two NRTIs and
      raltegravir (RAL), atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r).
      The primary outcome was time to discontinuation of the first-line regimen. The
      association between regimen type and duration was estimated using Cox
      proportional hazards models adjusted for age, gender, baseline CD4, baseline
      viral load, risk factor, site and year of treatment initiation. RESULTS: A total
      of 743 patients (281 on STRs and 462 on non-STRs) were included. 693 (93%) were
      male and median age was 43 years. Median length of follow-up was 3.2 years. 56%
      of patients were MSM, 6% IDU and 6% from endemic countries. Patients on an STR
      were less likely to be IDU (p<0.024) and have a baseline HIV-RNA >=100,000
      copies/mL (p<0.011). Overall, 321 (43%) patients discontinued their regimen
      during the study period. The rate of discontinuation one year after starting ARV
      depends on the regimen: 29% for patients on 2NRTIs+DRV/r, 26% on ATP, 25% on
      2NRTIs+ATV/r, 17% on 2NRTIs+RAL and 10% on CPLR (p<0.001). In the adjusted model,
      durability for STR and non-STR was equivalent (aHR=0.83, p=0.108). Compared to
      patients on ATP, patients on CPLR were less likely to discontinue (HR=0.58,
      p=0.070). No difference between ATP and the other regimens was observed: HR for
      2NRTIs+RAL=0.92 (p=0.66), 2NRTIs+ DRV/r=1.16 (p=0.36), 2NRTIs+ATV/r=1.11
      (p=0.46). CONCLUSIONS: Our findings suggest that STRs do not necessarily result
      in a more durable treatment. Even with a higher pill burden and/or twice daily
      dosing, patients initiating therapy with RAL or boosted-PI based regimens were
      not more likely to discontinue the first-line regimen compared to patients on an
      STR. Among the STR subgroups, the regimen with better known tolerability
      conferred more durable treatment. Limitations included our inability to adjust
      for the patient's adherence to a given regimen.

PMID- 25397510
TI  - Can we trust the guidelines? Comparison between the data presented and the
      recommendations of the International Antiviral Society-USA Panel.
AB  - INTRODUCTION: Clinicians often do not have the time and possibilities to read all
      scientific evidence necessary to maintain high quality patient care. They rely on
      guidelines made by experts to help them in their daily work. METHODS: We compared
      the 2012 recommendations and the arguments of the IAS-USA Panel with the data
      referenced and presented with the original data of the studies. Special topic was
      the timing of antiretroviral therapy. Only studies included in the guideline text
      were analyzed. RESULTS: There is a large discrepancy between the data and the
      recommendations concerning early antiviral therapy. The studies are either not
      designed to answer this question or the data is not sufficient to support the
      arguments. The authors highlight benefits without mention of side effects or
      other problems. Neither in transmission rates, nor mortality, AIDS events, co
      morbidities (hepatitis B and C excluded) or decreasing the risk of malignancy,
      the data presented support early therapy. CONCLUSIONS: A large discrepancy
      between the underlining data and the recommendation made by the IAS-USA Panel
      exists concerning early antiviral therapy.

PMID- 25397511
TI  - Long-term efficacy and safety of E/C/F/TDF vs EFV/FTC/TDF and ATV+RTV+FTC/TDF in
      HIV-1-infected treatment-naive subjects >=50 years.
AB  - INTRODUCTION: In high-income countries, >=30% of HIV-infected patients are >=50
      years (yrs) old (UNAIDS 2013). In two phases, three clinical trials (Studies 102
      and 103) elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF; STB) had
      non-inferior efficacy and favourable safety vs efavirenz/emtricitabine/tenofovir
      DF (EFV/FTC/TDF; ATR) or ritonavir-boosted atazanavir (ATV+RTV)+FTC/TDF (TVD) in
      HIV-infected, treatment-naive subjects at Week 144. The efficacy and safety of
      STB in subjects < or >=50 yrs is described. MATERIALS AND METHODS: Post hoc
      analysis of efficacy, tolerability and safety in subjects < or >=50 yrs at Week
      144. RESULTS: Subjects >=50 yrs in Study 102: STB: 14% (49/348), ATR: 16%
      (56/352); in Study 103: STB: 14% (48/353), ATV+RTV+TVD: 14% (48/355). Efficacy,
      safety and tolerability by age and study endpoint are shown in Table 1.
      Regardless of age, STB had robust efficacy at Week 144 with similar virologic
      outcomes vs ATR or ATV+RTV+TVD. Discontinuations (DC) due to AE on STB were
      similar to the comparators, most occurred by Week 48. Median changes in eGFR on
      STB were similar by age; DC with renal PRT was rare [STB: 4 (0.6%); ATV: 3
      (0.8%); ATR: 0], 2 and 1 in >=50 yrs old strata, respectively. CONCLUSIONS: STB
      compared to ATR or ATV+RTV+TVD, is an efficacious, well-tolerated and safe
      regimen for HIV-1-infected, treatment-naive subjects<or>=50 yrs of age.

PMID- 25397512
TI  - Treatment modification in HIV-Infected individuals starting antiretroviral
      therapy between 2011 and 2014.
AB  - INTRODUCTION: While antiretroviral therapy (ART) has increased the survival of
      HIV patients and turned HIV infection into a chronic condition, treatment
      modifications and poor adherence might limit this therapeutic success. METHODS:
      Patients from the Austrian HIV Cohort Study, who started their first ART after
      Rilpivirine became available in February 2011, were analyzed for factors
      associated with treatment modification which could be either a change of drugs or
      a stop of the regimen. A drug was considered as stopped when the regimen was
      interrupted for more than eight days. Drugs of particular interest were Darunavir
      (DRV), Atazanavir (ATV), Raltegravir (RAL), Rilpivirine (RPV) and Efavirenz
      (EFV). RPV and EFV were analyzed only when taken as single tablet regimen. Other
      drugs were summarized as "other." Proportional hazards regression methods were
      used to identify predictors of discontinuation and Kaplan-Meier estimates were
      used to calculate probabilities of discontinuation. Patients who died were
      censored at the date of death. RESULTS: 965 patients started ART, 282 with DRV,
      161 with ATV, 96 with RAL, 108 with RPV and 118 with EFV. Median time for taking
      initial ART is 11.6 months. 322 (33.4%) patients modified their initial ART. The
      overall probability of modification at one year was 28.7%, at two years 40.0% and
      at three years 49.8%. In a multivariable proportional hazards regression
      analysis, AIDS diagnosis at baseline and injecting drug use (IDU) of men compared
      with men who have sex with men (MSM) have a higher risk of switch/stop. Compared
      with DRV, RPV showed a much lower and ATV and particularly "other" a higher risk
      for discontinuation (Table 1). CONCLUSION: Rates of modification and interruption
      were still high in recent years, particularly in the first year of ART. The
      decreased rate of modification found in patients treated with Rilpivirine may be
      attributed to selection of patients according to guidelines.

PMID- 25397513
TI  - Increased risk of virological failure to the first antiretroviral regimen in HIV
      infected migrants compared to natives: data from the ICONA cohort.
AB  - INTRODUCTION: Aim of the study was to evaluate possible disparities in access
      and/or risk of virological failure (VF) to the first antiretroviral (ART) regimen
      for migrants compared to Italian-born patients and to assess determinants of
      failure for the migrants living with HIV. METHODS: All native and migrant naive
      patients enrolled in ICONA in 2004-2014 were included. Firstly, variables
      associated to ART initiation were analyzed. In a second analysis, the primary
      endpoint was time to failure after at least six months of ART, defined as: (a) VF
      (first of two consecutive viral load (VL) >50 and >200 copies/mL); (b) treatment
      discontinuation (TD) for any reason; and (c) treatment failure (TF: confirmed VL
      >200 cp/mL or TD). A Poisson multivariable analysis was performed to control for
      confounders. RESULTS: A total of 5777 HIV-pos ART-naive patients (1179 migrants
      and 4598 natives) were evaluated. Most migrants were from sub-Saharan Africa
      (35.3%) and South-Central America/Caribbean (29%). Median duration of residency
      in Italy was five years (IQR 1-10). Baseline characteristics significantly
      differed between the two groups (Table 1); in particular, lower CD4 counts and
      higher frequency of AIDS events were observed in migrants vs natives. When
      adjusting for baseline confounders, migrants presented a lower chance to initiate
      ART compared to natives (OR 0.78, 95% CI 0.65-0.93, p=0.006). After ART
      initiation, the incidence rate of VF >50 cp/mL was 15.5 per 100 person-years (95%
      CI 12.8-18.8) in migrants and 8.9 in natives (95% CI 7.9-9.9), respectively. By
      multivariable analysis, migrants had a significantly higher risk of VF, both >50
      cp/mL (OR 1.50, 95% CI 1.17-1.193, p=0.001) and >200 cp/mL (OR 1.59, 95% CI 1.23
      2.05, p<0.001), and of TF (OR 1.15, 95% CI 1.00-1.32, p=0.045), while no
      differences were observed in TD risk. Among migrants, variables associated with a
      higher VF risk were age (for 10-year increase, OR 0.96, 95% CI 0.93-0.98,
      p=0.002), unemployment (OR 1.96, 95% CI 1.20-3.20, p=0.007) and use of a boosted
      PI based-regimen (OR 2.04, 95% CI 1.25-3.34, p=0.005 vs NNRTI-based), while
      pregnancy was associated with TD (OR 3.73, 95% CI 2.36-5.90, p<0.001) and TF (OR
      3.13, 95% CI 02.00-4.89, p<0.001). CONCLUSIONS: Despite the use of more potent
      and safer antiretroviral drugs in the last 10 years, and even in a setting of
      universal access to ART, migrants living with HIV still present barriers to ART
      initiation and increased risk of VF compared to natives.

PMID- 25397514
TI  - 144-week outcomes of lopinavir/ritonavir (LPV/r)-based first-line ART in 1,409
      HIV-infected patients: data from the German STAR/STELLA cohort.
AB  - INTRODUCTION: STAR/STELLA is a prospective[TS1] cohort of HIV patients initiated
      on LPV/r-based ART in routine clinical practice. Here, virologic/immunologic
      outcomes and safety data of LPV/r-based first-line ART over a period of 144 weeks
      are presented. METHODS: Analysis included ART-naive patients who started on LPV/r
      before July 2011 (i.e. patients with >=144 weeks since ART initiation). Safety
      evaluation included adverse events (AEs), discontinuations (disc.) due to AEs,
      and symptoms assessed with the self-report ACTG Symptom Distress Module (ASDM;
      high score=high distress). RESULTS: 1409 patients were included (84% men; 76% on
      TDF+FTC), with a large proportion in advanced stages of HIV disease at ART
      initiation: 48% had a CD4 count <200/uL, 55% had HIV RNA levels >100,000 c/mL.
      53% of patients (n=746) remained on LPV/r for at least 144 weeks. Time on drug
      was longer for patients initiated before 2008 than in subsequent years (HRadj,
      1.2; 95% CI, 1.0-1.4; p=0.04; hazard ratio adjusted for CD4 <200/uL and HIV RNA
      >100,000 c/mL). Main reasons for d/c were: AEs (19.3%), patient wish (9.2%),
      virologic/immunologic failure (4.1%), and noncompliance (2.8%); 1.6% of patients
      died. By week 144, 33% of patients had >750 CD4/uL (Kaplan-Meier estimate): time
      to CD4 count >750 c/ uL, stratified by BL CD4 count, is shown in Figure 1.
      CONCLUSION: In the STAR/STELLA observational cohort, LPV/r-based ART demonstrated
      good virologic outcomes and immune recovery in ART-naive patients over 144 weeks,
      with significant improvements in symptom distress. Over three years, <5% of
      patients discontinued LPV/r due to virologic/immunologic failure, and 19% of
      patients discontinued for tolerability reasons.

PMID- 25397515
TI  - An observational comparison of first-line combination antiretroviral treatment
      (cART) with 2NRTI and ATV/r or DRV/r in HIV-infected patients in Italy.
AB  - INTRODUCTION: In a recent clinical trial (ACTG 5257), no difference in viral
      failure (VF) of a first-line cART containing atazanavir/r (ATV/r) or darunavir/r
      (DRV/r) was found [1]. For the endpoint of discontinuation due to intolerance,
      the regimen with DRV/r was superior to that of ATV/r (49% of the stops of ATV/r
      were attributed to jaundice or hyperbilirubinemia). These and other intolerances
      to ATV/r remain a concern for clinicians. METHODS: Participants in the ICONA
      Foundation Study who started cART with 2NRTI+ ATV/r or DRV/r while ART-naive were
      included. Several endpoints were evaluated: confirmed VF>200 copies/mL after six
      months of therapy, discontinuation of DRV/r or ATV/r for any reasons or because
      of intolerance/toxicity (as reported by the treating physician) and the combined
      endpoint of VF or stop. Survival analysis with Kaplan-Meier curves and Cox
      regression model stratified by clinical site was used. Patients' follow-up
      accrued from cART initiation to the date of the event or to the date of last
      available visit/viral load. RESULTS: 894 patients starting 2NRTI+ATV/r and 686
      2NRTI+DRV/r when ART-naive on average in 2011 (IQR: 2010-2012) were studied. Most
      common NRTIs used were FTC/TDF (84%) and ABC/3TC (12%). Median age was 40 years,
      22% females, 44% heterosexuals. Patients starting ATV/r were more likely to be
      hepatitis B/C infected (2% and 14% vs 1% and 9%, p=0.001), they started one year
      earlier (2011 vs 2012, p=0.001), were more likely to be enrolled in sites located
      in the north of Italy (63% vs 54%, p=0.04), started cART less promptly after HIV
      diagnosis (5 vs 2 months, p=0.02) and less likely to have started TDF/FTC (83% vs
      85%, p=0.02). By two years of cART, 9.8% (95% CI 7.6-12.0) of those starting
      ATV/r experienced discontinuation due to intolerance/toxicity vs 6.5% in DRV/r
      group (95% CI 4.2-8.8, p=0.04). After controlling for several potential
      confounders (age, gender, nation of birth, mode of HIV transmission, hepatitis co
      infection status, AIDS diagnosis, nucleoside pair started, baseline CD4 count and
      viral load and year of starting cART) the relative hazard (RH) for ATV/r vs DRV/r
      was 2.01 (95% CI 1.23, 3.28, p=0.005). There were no statistical differences
      detected for any of the other outcomes. CONCLUSIONS: Although unmeasured
      confounding cannot be ruled out, our results seem to be consistent with those of
      the ACTG 5257. When all cause discontinuations were considered, or the composite
      endpoint of treatment failure, there was no difference between ATV/r- and DRV/r
      based regimens.

PMID- 25397516
TI  - Phase IIIb, open-label single-arm trial of darunavir/cobicistat (DRV/COBI): Week
      48 subgroup analysis of HIV-1-infected treatment-nave adults.
AB  - INTRODUCTION: COBI, a PK enhancer with no ARV activity is a more selective
      cytochrome P450 (CYP)3A inhibitor than ritonavir (RTV), does not induce CYP
      isozymes, and thus has less potential for drug-drug interactions. COBI boosts DRV
      PK as effectively as RTV in healthy volunteers. MATERIALS AND METHODS: This 48
      week, phase IIIb, open-label, single-arm, US multicentre study (NCT01440569)
      included HIV-infected treatment-nave and experienced adults with no DRV RAMs,
      viral load (VL) >=1000 c/mL, eGFR >=80 mL/min and genotypic sensitivity to
      investigator-selected N[t]RTIs. Patients received DRV/COBI 800/150 mg qd (as
      single agents) plus two fully active N[t]RTIs. The primary endpoint was any
      treatment-emergent grade 3 or 4 AEs through Week 24. We report 48-week safety,
      efficacy and PK/PD results in treatment-nave patients. RESULTS: Of 313 ITT
      patients, 295 were treatment-nave (94%). In the treatment-nave cohort, 90% were
      male, 60% white and 294 (99.7%) received a TDF-containing regimen. Median
      baseline (BL) VL was 4.8 log10 c/mL and CD4(+) 370 cells/mm(3). Treatment
      emergent grade 3 or 4 AEs regardless of causality were reported in 21 (7%)
      patients. AEs regardless of causality (any grade; >=10% of patients) were:
      diarrhoea (27%), nausea (23%), URTI (15%) and headache (12%). Sixteen (5%)
      patients had AEs leading to study drug discontinuation, most frequently rash
      (three patients), hypersensitivity and nausea (two patients each). Consistent
      with the known inhibition of tubular creatinine secretion by COBI, there was a
      mean increase from BL in serum creatinine by week 2 (0.09 mg/dL), remaining
      stable through week 48 (mean 0.10 mg/dL increase from BL). At week 48, 83% of
      patients achieved VL<50 c/mL; FDA Snapshot); median increase in CD4(+) was 169
      cells/mm(3). Eight patients met the criteria for resistance testing. M184V was
      detected in one pt receiving FTC. New primary RAMs were not detected in the other
      seven patients. The mean population PK-derived DRV AUC24h was 100,620 ng.h/mL and
      C0h 2,105 ng/mL (n=281). There were no clinically relevant relationships between
      DRV exposure and virologic response, AEs or laboratory parameters. CONCLUSIONS:
      The DRV PK of DRV/COBI was consistent with historical data for DRV/RTV. DRV/COBI
      800/150 mg qd plus two N(t)RTIs had an 83% response and was well tolerated
      through Week 48. These results are similar to published data for DRV/RTV 800/100
      mg qd, and support the use of DRV/COBI 800/150 mg qd in treatment-nave patients.

PMID- 25397517
TI  - Effectiveness and tolerability of abacavir-lamivudine-nevirapine (ABC/3TC/NVP) in
      a multicentre cohort of HIV-infected, ARV-naive patients.
AB  - PURPOSE: Very scarce information has been published to date with the combination
      of ABC/3TC/NVP but it is currently being used in clinical practice in Spain and
      Portugal. Our aim was to present the clinical experience with this regimen in a
      cohort of adult HIV-infected antiretroviral (ARV)-naive patients. METHODS:
      Retrospective, multicentre, cohort study. Consecutive adult HIV-infected ARV
      naive HLA-B*5701-negative patients, who started ABC/3TC/NVP between 2005-2013,
      with at least one follow-up visit, were included. Demographic, clinical and
      laboratory variables were assessed at baseline, month 1, and every three-four
      months thereafter. The primary end point was HIV-1 viral load (VL)<40 c/mL at 48
      weeks. Data were analyzed by intent-to-treat (ITT) (switch=failure, and
      missing=failure) and on treatment (OT) analyses. RESULTS: 78 patients were
      included. Median follow up was 26 (0.1-84) months. 86% were male, median age 41
      (23-69) years, 9% had AIDS, 8% were HCV+, baseline CD4 was 275 (10-724) cells/uL
      and median VL 4.58 (3.02-6.92) log. After 48 weeks, VL was<40 c/mL in 89.8% (OT),
      79.7% (M=F) and 65.4% (S=F) and at 96 weeks in 88.5%, 78.9% and 61.6%,
      respectively. CD4 increased +246 (p<0.001) and +292 (p<0.001) cells/uL after 48
      and 96 weeks, respectively. One or more drugs of the regimen were discontinued in
      33 (42.3%) patients. In 15 (19.2%) patients (13 NVP, 2 ABC/3TC) therapy was
      stopped due to toxicity after a median of one month (in only two cases after six
      months of follow up): 80% of them had rash/liver toxicity. Six (7.7%) patients
      discontinued ART due to virologic failure, five (6.4%) because of other reasons
      and seven (9%) were lost to follow-up. ALT but not AST significantly increased
      (+0.07 ukat/L at 96 weeks, p=0.033). A significant increase of 25%, 26% and 42%
      in total cholesterol, LDLc and HDLc, respectively, and a significant decrease in
      TC/HDL ratio (6%, p=0.008) was observed after 96 weeks. CONCLUSIONS: Despite a
      considerable proportion of patients had to stop therapy due to toxicity (most
      associated with NVP), those initially tolerating this regimen presented a high
      virologic and immunologic response after 96 weeks, as well as a favourable lipid
      profile. ABC/3TC/NVP may be a suitable alternative first regimen, mainly in
      countries with economic constraints.

PMID- 25397518
TI  - Four-drugs regimen containing raltegravir is highly effective in HIV patients
      starting therapy with >500,000 copies/mL viral load.
AB  - INTRODUCTION: Assessing virological response of four-drugs antiretroviral regimen
      that include raltegravir (RAL) in naive patients with high viral load (>500,000
      copies/mL) selected from a multicentre Italian database. METHODS: Naive patients
      with HIV RNA>500,000 copies/mL, who began standard antiretroviral regimens either
      based on non-nucleoside reverse transcriptase inhibitors (NNRTI) or boosted-PI
      (PI/r), or a standard regimen plus RAL between 2008 and 2013 were analyzed.
      Observation was censored at 12 months and the percentage of patients who achieved
      a viral load below the limit of detection (BLD) was calculated. Virological
      failure was defined as two consecutive viral loads>40 copies/mL. RESULTS:
      Overall, 179 patients were included (13% with primary HIV infection (PHI), and
      42.5% with AIDS diagnosis). Of them, 156 started standard three-drugs
      antiretroviral regimen (75.6% PI/r-based, 24.4% NNRTI-based. Among patients with
      PHI, 23 patients (12.8%), 6 (25%) started a four-drugs antiretroviral regimen
      containing both RAL and PI/r. Patients' characteristics were as follows: males
      74%, median age 42 years (IQR 35-51), sexually transmission 75.1%, median CD4
      count 156 cells/uL (IQR 47-368) and median HIV-RNA 6.1 log10 copies/mL (IQR 5.8
      6.4). 91 of 179 patients (50.8%) reached BLD viral load during the twelve months
      of observation. Three patients (1.7%) who began regimens PI/r-based with three
      drugs had virological rebound after reaching BLD viral load. By use of survival
      analysis, we show that those patients who added RAL to the standard regimen have
      reached the primary end point faster (mean 8.4 months (95% CI 7.2-9.6) vs 11.4
      (95% CI 11.0-11.8) in PI group and 10.3 (95% CI 9.4-11.1) in NNRTI group;
      p<0.001, Figure 1). In the adjusted analysis, the choice of a standard regimen
      versus a four-drugs regimen was driven only by higher baseline viral load (OR.
      9.05; 95% CI 2.41-37.41; p=0.001). CONCLUSIONS: Only half of the naive patients
      who began antiretroviral therapy having >500,000 copies/mL HIV-RNA had
      virological success at 12 months. The success was reached faster using the RAL
      containing four-drugs regimen, suggesting that strengthening the initial regimen
      could be an option in patients with very high viral load to improve virological
      response. Probability of HIV viral load below the limit of detection in naive HIV
      1 patients with viral loads >500,000 copies/mL treated with a 4-drugs regimen
      containing raltegravir versus standard therapy with PI/ or NNRTI.

PMID- 25397519
TI  - Determinants of use of the fixed dose combination
      emtricitabine/rilpivirine/tenofovir (Eviplera) in HIV-infected persons receiving
      care in Italy.
AB  - INTRODUCTION: Emtricitabine/rilpivirine/tenofovir (EVP) is a fixed-dose
      combination of antiretrovirals (ARV) approved by the European Medicines Agency in
      November 2011 and introduced in Italy in February 2013. It is a once-a-day single
      tablet and is licensed in Europe for use only in ARV-naive patients with a viral
      load (VL) <=100,000 copies/mL. OBJECTIVE: To identify factors that may be
      associated with the use of EVP as first-line regimen in HIV-infected individuals
      starting cART from ARV-naive in Italy. METHODS: Clinical sites in ICONA
      Foundation Study in which >=1 person had started EVP were selected for this
      analysis. From these we included all patients who started an EVP-based cART
      regimen as well as those starting other cART regimens after the date of
      introduction of EVP at the site (after February 2013 in any case) and with a VL
      <=100,000 copies/mL from ARV-naive. Characteristics at the time of starting cART
      were compared using chi-square test and unadjusted and adjusted logistic
      regression analysis. Factors investigated included: gender, mode of HIV
      transmission, time from HIV diagnosis, CD4 count, nation of birth, AIDS, HCV
      status, age, CD8 count, VL, diabetes, smoking, total and HDL cholesterol, eGFR,
      blood glucose, level of education and employment and site location. Factors
      showing unadjusted associations with a p-value of 10% or smaller, were retained
      in the multivariable model. RESULTS: We identified 183 patients starting EVP and
      173 starting the control regimen from 23 sites. The number of patients starting
      EVP included at each site ranged from 1 to 12 and the number of those starting
      the control regimen was similar. The most frequently used drugs in the concurrent
      group were: TDF (75%), FTC (74%), DRV (39%), ATV/r (26%), LPV/r (9%), EFV (13%)
      and RAL (14%). In univariable analysis, there were differences in median CD4
      count (390 cells/mm(3) in EVP versus 348 in controls, p=0.002), time from HIV
      diagnosis to starting cART (11 versus 3 months, p=0.001) and prevalence of
      students (6% versus 3%, p=0.07). No differences were observed for all other
      factors examined. The table shows estimates of the odds ratios (OR) for factors
      included in the multivariable model. CONCLUSIONS: CD4 count was higher in EVP
      treated patients compared to controls. Guidelines suggest avoiding initiation of
      EVP in presence of high VL, possibly explaining this residual difference in CD4.
      There was also a tendency to prescribe EVP to people with perceived lower
      adherence or hesitant to start or perhaps with a slow progressing disease.

PMID- 25397520
TI  - Long-term effect of a four-drugs induction regimen for patients with high
      baseline viral load.
AB  - INTRODUCTION: The long-term effects of an intensified induction regimen are
      unknown. In this pilot, randomized, prospective study we evaluate the effect of a
      short-term four-drugs induction regimen in patients with high baseline viral
      load. METHODS: Naive patients with HIV-RNA>100.000 copies/ml receiving
      TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV.
      Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or
      TDF+FTC+RAL (R) were used. RESULTS: 19 patients with a mean age of 38 years and
      mean baseline CD4 count of 334 (SD 216) cells/mcL and HIV-RNA of 5.47 log (SD
      0.32) copies/mL were enrolled. No baseline significant difference was observed
      among groups. Early HIV-RNA reduction was significantly higher in ER compared to
      the other groups from week 1 to week 4 (P from 0.026 to 0.003) (figure 1),
      thereafter HIV-RNA values were comparable among the groups. At week 96, all
      patients had an HIV-RNA < 50 copies/mL, however only patients in the ER group had
      in all cases an HIV-RNA level < 3 copies/mL with a statistically significant
      difference compared to E (60%; P=0.038) and R (50%; P=0.020). At 96 weeks, CD4
      cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R
      (P=0.16), however patients in the ER group presented a lower proportion of
      activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8%) and CD8+CD38+HLADR+
      cells (10.3% versus 16.8 and 16.5%) and a significantly better CD4/CD8 ratio
      (0.98 versus 0.53 and 0.61; P=0.03). CONCLUSIONS: A four-drug regimen in naive
      patients with high pre-therapy viral load improves early virologic response. A
      quick drop of HIV-RNA seems to correlate with a sustained virologic response.
      Although limited in time (four months), the four-drug regimens correlates with an
      improved immunological response as measured by the CD4/CD8 ratio or the
      percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve
      further studies. This study highlights the importance of a personalised therapy
      especially in high risk patients.

PMID- 25397521
TI  - Who gets single tablet regimens (STR), and why?
AB  - INTRODUCTION: The BHIVA guidelines now feature three single tablet regimens
      (STRs) as recommended treatments for HIV-positive people new to therapy [1]. They
      are popular with patients and are attractive in a number of clinical scenarios.
      We sought to determine how our use of STRs had developed over a three-year
      period, and how the decision to opt for an STR was made. METHODS: Retrospective
      case-note review and database interrogation of all patients starting anti
      retroviral therapy (ART) from 1st March 2011 to 31st March 2014. RESULTS: 215
      patients started ART. 58% (125/215) were black-African and 47% (100/215) were
      female. Median CD4 at baseline was 272 cells/uL (range 1-1044 cells/uL). 69 (32%)
      had a viral load (VL) >100,000 copies/mL. 7 individuals had evidence of
      transmitted drug resistance. 88 patients started an STR. Two tested positive for
      HLAB5701. None had a 10 year CVS risk score of >20% and 36% had a baseline VL
      >100,000 copies/mL. 127 patients started a non-STR regimen, 29% had a VL >100 000
      copies/mL and none had an elevated CVS risk. Information regarding baseline renal
      function and HLAB5701 will be provided at the conference. The use of STRs
      increased over the three years (25% 2011-12; 57.1% 2012-13; 44% 2013-14). There
      was no difference in STR prescribing between men and women. In men, heterosexual
      male patients were more likely to be prescribed an STR than MSM males (54% versus
      43%, p 0.005). In 43% (38/88) patients had indicated a preference for an STR and
      32/88 expressed a preference for a particular drug. 2% (2/88) requested to be on
      the same treatment as a partner. In those patients who expressed an interest in a
      particular drug, four had received information from a friend or partner. In 33%
      (29/88) cases an STR was felt by the clinician to be the best option, largely
      based on concerns around pill-burden and adherence (31%), viral load (16%) and
      renal or cardiac risk (7%). CONCLUSIONS: Use of STRs is increasing. This is not
      driven on in our cohort by cardiovascular risk of HLAB5701 carriage but by
      patient and clinician preference, and to a lesser extent by higher baseline viral
      loads.

PMID- 25397522
TI  - Treatment outcome in HIV+ patients receiving 3- or 4-drug regimens during PHI.
AB  - INTRODUCTION: The optimal timing and modality of therapeutic intervention during
      early phases of HIV infection is still debated; in our prospective observational
      study we evaluated immunological and virological outcome in HIV+ patients treated
      during acute or recent HIV infection. MATERIALS AND METHODS: A total of 25 naive
      patients with acute (detectable HIV-RNA, immature Western Blot) or recent
      (documented infection within six months) HIV infection were recruited at the
      Infectious Diseases Units of the University of Milan and Turin from 2009 to 2014.
      Patients received treatment with two NRTIs+one NNRTI/bPI, with or without an
      induction phase with an additional fourth drug (raltegravir or maraviroc) until
      HIV-RNA undetectability maintained for six months. Blood samples for HIV-RNA,
      lymphocyte subsets and tropism assessment were obtained at the beginning of the
      treatment (BL). Patients underwent subsequent six-monthly follow up for clinical
      outcome, CD4 cell count and HIV-RNA up to 18 months. RESULTS: Median increase in
      CD4 cells from 0 to 12 months was greater in patients treated during acute (n=18)
      versus recent (n=7) infection [284/uL, IQR (227-456) versus 176/uL, IQR (70-235);
      Mann-Whitney test, p=0.046]. This higher value was maintained through 18 months,
      although failing to reach statistical significance. Patients with acute or recent
      infection did not significantly differ in virological success (83.3% versus 85.7%
      at 12 months). We considered CD4 cells gains at six months (multivariate
      analysis, ANCOVA; Figure 1) and detected an inverse correlation with CD4 levels
      at BL (r=-0.517; p=0.008) and a direct correlation with the status of acute
      infection (r=0.234, p NS). This last correlation reached statistical significance
      at 12 months (r=0.418, p=0.035), whereas the inverse correlation with CD4 levels
      at BL was still present without a statistical significance (r=-0.350; p=0.072).
      Patients treated with three or four drugs did not show any significant difference
      in immunological nor virological response (Mann-Whitney and chi(2) test).
      Modification or interruption of therapy for tolerability took place in 4 out of
      25 patients, all while receiving four drugs; two patients underwent STI between
      12 and 18 months following virological success. CONCLUSIONS: Treatment of primary
      infection appeared to be effective in preserving the pool of CD4 cells in acute
      more than recent infection. There was no evidence of a different outcome through
      the addition of a fourth drug to the standard treatment.

PMID- 25397523
TI  - An indirect comparison of efficacy and safety of
      elvitegravir/cobicistat/emtricitabine/tenofovir and dolutegravir +
      abacavir/lamivudine.
AB  - BACKGROUND: Integrase strand transfer inhibitors (INSTI) are the standard of care
      for naive HIV-infected individuals due to their favourable efficacy and safety
      profile. The newest INSTIs, elvitegravir and dolutegravir, have not been
      evaluated in a head to head study; however, both have been compared to
      efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF) in phase III trials.
      Elvitegravir/cobicistat/emtricitabine/tenofovir DF (E/C/F/TDF) was compared to
      EFV/FTC/TDF for 144 weeks in Gilead Study 102 (GS-102), while dolutegravir (DTG)
      with the abacavir/lamivudine fixed-dose combination (ABC/3TC) was compared to
      EFV/FTC/TDF for 96 weeks in the SINGLE study. The objective of this analysis is
      to perform an indirect comparison at 48 and 96 weeks of E/C/F/TDF to DTG+ABC/3TC
      by using the two trials evaluating each of these regimens compared to
      EFV/FTC/TDF. METHODS: An indirect comparison was performed by using Bucher's
      methodology to calculate risk differences based on the two phase III clinical
      trials described above. RESULTS: At week 48 (snapshot analysis), 88% of the
      patients on E/C/F/TDF and DTG+ABC/3TC had HIV RNA <50 c/mL, while 84% and 81% of
      patients on EFV/FTC/TDF were suppressed in GS-102 and SINGLE, respectively. At
      week 96, 84% of patients receiving E/C/F/TDF compared with 80% of patients
      receiving DTG+ABC/3TC remained suppressed, while 82% and 72% on EFV/FTC/TDF
      maintained HIV RNA <50 c/mL in GS-102 and SINGLE. At week 144 80% of patients on
      E/C/F/TDF remained suppressed (vs. 75% of the patients on EFV/FTC/TDF). RESULTS
      of indirect comparison showed a risk difference of HIV RNA <50 copies per mL
      between E/C/F/TDF compared with DTG+ABC/3TC of -4% (CI 95%=-11 to 3) for the ITT
      48 weeks (p=0.3) and -5% (95% CI=-13 to 3) for the ITT 96 weeks (p=0.2). In
      regards to safety, there was no significant difference between E/C/F/TDF and
      DTG+ABC/3TC for any adverse event (AE) (p=0.3), serious AEs (0.13), drug related
      AEs (0.7), or drug-related serious AEs (0.6). CONCLUSIONS: In GS-102 and SINGLE,
      88% of the patients on E/C/F/TDF and DTG+ABC/3TC were virologically suppressed at
      week 48. At week 96, these proportions were 84% for E/C/F/TDF and 80% for
      DTG+ABC/3TC. The indirect efficacy comparisons between EVG/COBI/FTC/TDF and
      DTG+ABC/3TC at week 48 and 96 revealed no statistically significant differences.

PMID- 25397524
TI  - Efficacy and tolerability of Etravirine in HIV-1 adult patients: Results of a
      large French prospective cohort.
AB  - BACKGROUND: IEtravirine (ETR) was approved in France in Sept 2008, to be used in
      combination with a ritonavir-boosted protease inhibitor (bPI) and others
      antiretrovirals (ARV) in HIV-infected pre-treated patients. OBJECTIVES: To
      describe in a real life setting efficacy and tolerability of ETR-including
      regimen and factors associated with virologic response. METHOD: In the French
      DatAIDS cohort including 18,647 patients, we selected patients who initiated an
      ETR-including regimen between September 2008 and July 2013. Demographic data and
      clinico-biological data were collected from the standardized electronic medical
      record Nadis((r)). Analyses were done in patients starting ETR and sub-analyses
      were performed in pre-treated patients starting ETR for virologic failure (VF) or
      maintenance (MT) therapy, with or without bPI. RESULTS: 2083 patients (ARV-naive
      n=77, VF n=1014, MT n=992) were included: median age 47 years, 73.3% male, median
      duration of HIV infection 15.7 years, CDC stage C 38.7%, HBV/HCV co-infection
      25.7%. In pre-treated patients, 75.5% previously received NNRTIs (median duration
      on EFV and NVP of 480 and 396 days, respectively), 94.3% bPIs, 30.8% raltegravir
      (RAL) and 19.4% enfuvirtide. The most frequent ARVs associated with ETR were two
      NRTIs in 37.2% of the cases (21.9% in VF, 52.9% in MT), 1 bPI+RAL in 10.1% (13.5%
      in VF, 6.6% in MT), RAL in 6.2% (2% in VF, 10.5% in MT). Median duration on ETR
      was 3.7 and 2.2 years in the VF and MT group, respectively. In the VF group, HIV
      RNA was <50 c/ml in 71.7% (71.1% without bPI, 72% with bPI) of the patients at
      M12, 72.8% (71% without bPI, 73.3% with bPI) of the patients at M24. In the MT
      group, HIV RNA was<50 c/ml in 90.5% of the patients at M12 and 93.1% at M24. ETR
      was discontinued in 8.8% of the patients (12.8% in VF, 5.4% in MT) for adverse
      events in 23.9% of cases (21.5% in VF, 29.5% in MT), treatment failure in 15.2%
      (16.2% in VF, 7.4% in MT) or simplification in 5.4% (4.6% in VF, 7.4% in MT). In
      the VF group, factors associated with virologic failure in multivariate analysis
      were a longer duration of HIV infection (OR 2.6; 95% CI 1.7-4.0) and baseline HIV
      RNA >5 log10 c/ml (OR: 2.0; 95% CI 1.3-3.2) but not the association with a bPI.
      CONCLUSION: This large study shows that in ARV-pre-treated patients ETR is well
      tolerated with a high efficacy when combined with other active drugs, even when
      the regimen does not include a bPI.

PMID- 25397525
TI  - Impact of etravirine use on hospitalization rates among highly pre-treated
      failing HIV-1 infected individuals between 2005 and 2011.
AB  - INTRODUCTION: Etravirine (ETR), a non-nucleoside reverse transcriptase inhibitor
      available in France since 2006, is indicated for the treatment of HIV-1 infection
      in combination with a ritonavir boosted protease inhibitor (PI) in antiretroviral
      treatment-experienced adult patients. To assess its impact in routine clinical
      care, our objective was to compare hospitalization rates in highly pre-treated
      failing HIV-1 infected individuals between 2005 and 2011 depending on whether or
      not they received ETR+PI. METHODS: From the French Hospital Database on HIV (ANRS
      CO4), we selected highly pre-treated individuals (prior exposure to at least
      2NRTI, 2PI and 1 NNRTI) with a viral load (VL)>50 copies/mL initiating a new
      regimen between 2005 and 2011. Hospitalization rates were calculated for each
      calendar month and depending on whether patients never received ETR+PI at any
      time or during months before initiating ETR+PI (no ETR+PI) or during months after
      initiating ETR+PI (ETR+PI), using an intention to continue treatment approach.
      Poisson regression models were used to compare incidence between the two groups,
      after adjustment for potential confounders (age, transmission group, origin,
      AIDS, PCP prophylaxis, viral load, CD4, nb of previous ARV). RESULTS: Overall
      3884 patients fulfilled inclusion criteria. Among them 838 (21.6%) received
      ETR+PI at least once. Among all enrolled patients, 35.8% had CD4 <200/mm(3),
      17.5% had VL >100,000 copies/ml, 42.8% had had an AIDS event and 47.8% had
      received more than 10 different antiretroviral drugs. There were 2484
      hospitalizations in 808 individuals over 13,986 patient-years. The
      hospitalization rates for 1000 P-Y were 169.0 for the ETR+PI group and 179.3 for
      the no ETR+PI group. After adjustment, the corresponding figures were 144.8 for
      1000 P-Y and 192.7 for 1000 P-Y respectively, with a relative risk estimated as
      0.75 (95% CI 0.67-0.84). CONCLUSIONS: Access to ETR+PI between 2005 and 2011 was
      associated with a 25% reduction in the hospitalization rate among highly pre
      treated failing HIV-1 infected individuals.

PMID- 25397526
TI  - Darunavir-based dual therapy in HIV experienced patients.
AB  - BACKGROUND: We assessed the virological response of DRV/r-based dual therapy in
      drug-experienced patients included in the Italian antiretroviral resistance
      database (ARCA). MATERIALS AND METHODS: Patients included in the study were
      treated with DRV/r in association with raltegravir (RAL), etravirine (ETV) or
      maraviroc (MAR) following treatment failure(s) and with a resistance test and at
      least one follow-up visit available. Observation was censored at last visit under
      dual therapy and survival analysis and proportional hazard models were used,
      taking virological failure (confirmed >50 c/mL HIV-RNA) as the end-point.
      RESULTS: Of the total 221 patients included, 149 (67.4%) started DRV/r with RAL,
      45 (20.4%) with ETV, 27 (12.2%) with MAR. Patients characteristics at the start
      of dual regimen were as follows: mean number of previous regimens, nine (IQR: 5
      13); non-B subtype, 17 (7.7%); median CD4 count, 347 (IQR: 246-544); undetectable
      viral load, 74 (33.5%). Full DRV/r resistance was detected in one (0.5%, HIV-DB
      interpretation system), 13 (5.9%, ANRS) and 17 patients (7.7%, Rega). 69
      virological failures (31.2%) were observed during follow-up. At survival
      analysis, the overall proportion of failure was 29.2% at one year and 33.8% at
      two years. The proportion of failure was lower in patients starting with
      undetectable versus detectable viral load (13.3% and 25.2% versus 37.4% and 38.8%
      at one and two years, respectively, p=0.001 for both analyses) and in patients
      treated with DRV 600 BID versus 800 QD (HR: 0, 56; 95% CI 0.31-0.99; p<0.05). By
      regimen, patients treated with DRV/r-RAL showed a non-significant lower
      proportion of failure (27.7% at one year, 32.0% at two years) if compared with
      DRV/r-MAR (35.9%, 47.1%) and DRV/r-ETV (34.1%, 34.1% at one and two years). In
      the adjusted proportional model, no significant difference among the three
      regimens was detected. A significant lower risk of failure was associated with
      higher overall GSS (HIV-DB HR: 0.53, 95% CI 0.32-0.88, p=0.014; Rega 0.60, 0.40
      0.88, p<0.01; ANRS 0.55, 0.34-0.90, p=0.017), while a higher risk of failure was
      associated with detectable HIV-RNA (3.02, 1.70-5.72, p<0.001). CONCLUSIONS: Among
      experienced patients, the best candidates to dual-therapy regimens including
      DRV/r are those with undetectable viral load and higher GSS. The association with
      RAL is the most commonly used but no clear advantage with respect to ETV or MAR
      was observed in our dataset, possibly due to the limited sample size.

PMID- 25397527
TI  - Week 48 results of a Phase IV trial of etravirine with antiretrovirals other than
      darunavir/ritonavir in HIV-1-infected treatment-experienced adults.
AB  - INTRODUCTION: In DUET, etravirine (ETR) 200 mg bid had durable efficacy and a
      favourable safety profile versus placebo, both arms with an optimised background
      regimen (BR) including darunavir/ritonavir (DRV/r). TMC125IFD3002 (VIOLIN;
      NCT01422330) investigated ETR plus ARVs other than DRV/r. MATERIALS AND METHODS:
      This was a 48 week, Phase IV, open-label, single-arm, multicentre study. HIV-1
      infected treatment-experienced adult patients on=8 weeks ARV therapy prior to
      screening, switching either for virologic failure (VF) (viral load [VL] =500
      c/mL) or regimen simplification/AEs (RS/AE) (VL<50 c/mL), received active ETR 200
      mg bid with an investigator-selected BR of =1 active ARVs, but excluding DRV/r or
      NRTIs only. The primary objective was to evaluate safety, tolerability and
      pharmacokinetics (PK). RESULTS: Of 211 treated patients, 55% were female, 61%
      black/African American. 155 patients (73%) had baseline (BL) VL=50 c/mL versus 56
      (27%) with BL VL<50 c/mL. Between these two latter subgroups, median BL VL was
      4.42 versus 1.28 log10 c/mL and CD4+ count 238 versus 410.5 cells/mm(3). Overall,
      96% previously used <2 NNRTIs and 99% used=5 PIs; median number of BL NNRTI RAMs
      was 2, PI RAMs 5 and NRTI RAMs 1. Overall, most common BR ARVs were PIs (83%),
      mostly lopinavir/r (62%) and mostly used alone (20%) or with 1 or 2 NRTIs (61%).
      Raltegravir was used in 9% of patients. Most frequent AEs (any cause/grade) were
      diarrhoea (17%) and URTI (8%). Incidence of grade 3-4 AEs was 13%, serious AEs 5%
      (no rashes; none ETR related), AEs leading to discontinuation 4%, AEs possibly
      related to ETR 23% and AEs of interest: rash (any type) 4%, hepatic 6% and
      neuropsychiatric 3%. At week 48, VF and RS/AE virologic responses (% patients
      with VL<50 c/mL; FDA Snapshot) were: 48% (74/155) and 75% (42/56), respectively.
      VF rates were 42% and 13%; 10% and 13% had no VL data in the week 48 window. The
      percentage of patients adherent to treatment (assessed based on PK sampling plus
      ETR pill count) was 47% (69/148) and 57% (30/53), in VF and RS/AE, respectively.
      Median CD4+ count (NC=F) increases were 0.0 and 24.0 cells/mm(3). In 29/49 of VFs
      with genotypic data at failure, ETR RAMs emerging in =5 patients were Y181C,
      E138A and M230L. The geometric mean ETR AUC12h was 4877 ng.h/mL and C0h 293 ng/mL
      (N=199). CONCLUSIONS: RESULTS of this study were consistent with those for ETR in
      other similar populations and support the use of ETR 200 mg bid with a non-DRV/r
      based BR.

PMID- 25397528
TI  - Gag drug resistance mutations in HIV-1 subtype C patients, failing a protease
      inhibitor inclusive treatment regimen, with detectable lopinavir levels.
AB  - The development of antiretroviral (ARV) drugs and their use in human
      immunodeficiency virus type 1 (HIV-1) has led to the effective control of HIV
      replication in infected patients. However the emergence of resistant HIV-1
      strains still remains a problem. Literature has shown that mutations may
      accumulate in the protease (PR) and gag regions of HIV-1 patients who fail
      therapy with protease inhibitor (PI) drugs (1, 2). Gag mutations have also been
      found to play an important role in the evolution of PI resistance (2). Despite
      this, the standard genotypic drug-resistance test examines mutations in the
      reverse transcriptase (RT) and PR region of HIV-1 and not gag (3). This study
      investigated the frequency of gag drug resistance mutations in the absence of
      major PI mutations in HIV-1 subtype C patients, failing a PI inclusive treatment
      regimen. Sixty-eight samples were retrieved from patients that were classified as
      second line treatment failures as they had a viral load greater than 1000
      copies?mL, as well as detectable lopinavir (LPV) levels. The gag and protease
      region of these patients were genotyped. Mutations in the gag and protease region
      were assessed using the REga Db sequencing tool and the CPR programme on the
      Stanford University HIV drug resistance database. The mean LPV level of these
      samples was 11.66 ug/mL. 69.11% (n=46) of the patients have no major PI mutations
      in protease. The following mutations that are associated with PI exposure were
      present in the data set: G62R (n=6), H219Q (n=11), S737T (n=8), I389T (n=8) and
      Q474L (n=7). Predictably, mutations that are associated with PI resistance were
      found, which are generally located in the p7/p1 and p1/p6 cleavage site. These
      mutations are K436R (n=4), I437V (n=1), L449P (n=5), R452K (n=4) and P453L?T
      (n=9). These results contribute to the knowledge of resistance mutations in gag
      and their impact on PI resistance. 

PMID- 25397529
TI  - Antiretroviral therapy (ART) management of Low-Level Viremia in Taiwan
      (ALLEVIATE).
AB  - INTRODUCTION: This retrospective study aimed to investigate that if switch of
      combination antiretroviral therapy (cART) would result in viral suppression (<40
      copies/mL) at 48 weeks for patients with persistent low-level viremia after
      having received cART for six months or more at two hospitals designated for HIV
      care in Taiwan. MATERIALS AND METHODS: Between January 2001 and January 2013,
      patients were enrolled if plasma HIV RNA load (PVL) were >20 to <1000 copies/mL
      detected for six months or more (1, 2). Using a standardized data collection
      form, we recorded data of PVL and CD4 count before cART and at the detection of
      low-level viremia, serologies for hepatitis B and C virus, risk factors, duration
      of cART exposure, years of HIV diagnosed and ever experiencing treatment failure.
      The strategy of switch is based on the clinical guidelines of BHIVA, which
      suggest change of cART from non-nucleoside reverse-transcriptase inhibitors
      (nNRTIs) or unboosted protease inhibitor (PI) to boosted PI, newer boosted PI or
      ARV of different mechanism (3). RESULTS: In this study, 165 patients were
      enrolled, 119 patients (72.1%) did not switch (Group 1), and 46 patients (27.9%)
      switched previous regimens to ARV of different mechanism (Group 2). The two
      groups differed significantly in the proportion of injecting drug users (IDU)
      (Group 1 vs Group 2, 10.9 vs 26.1%) and median PVL (67 vs 159 copies/mL), and the
      proportion of PVL<200 copies/mL (84.0% vs 58.7%) when low-level viremia was first
      detected. In Group 1, 39 (32.8%) continued two nucleoside reverse-transcriptase
      inhibitors (NRTIs) plus nNRTI; 29 (24.4%) 2 NRTIs plus PI, 47 (39.5%) 2 NRTIs
      plus boosted PI, and 4 (3.3%) 2 NRTIs plus integrase inhibitor (II). In Group 2,
      two (4.3%) switched to 2 NRTIs plus PI, 38 (82.6%) 2 NRTIs plus boosted PI, three
      (6.5%) 2 NRTIs plus II and three (6.5%) boosted PI plus II. In multivariate
      analysis, IDUs (adjusted odds ratio [AOR], 6.757; 95% CI 2.427-18.868) and PVL of
      200-999 copies/mL at enrollment (AOR, 4.902; 95% CI 1.992-12.048) were more
      likely to be switched. At 48 weeks, patients in Group 2 were more likely to
      achieve PVL<40 copies/mL than Group 1 (82.6% vs 63.0%, p=0.016), while no
      difference was observed in achieving PVL <200 copies/mL between the two groups
      (95.7% vs 92.4%, p=0.729). CONCLUSIONS: According to the clinical guidelines of
      BHIVA, patients with low-level viremia who switched to cART consisting of 2 NRTIs
      plus boosted PI or newer mechanisms were more likely to re-establish viral
      suppression to <40 copies/mL at week 48.

PMID- 25397530
TI  - Effectiveness and durability of darunavir/ritonavir (DRV/r) in DRV/r-experienced
      HIV-1-infected patients in routine clinical practice.
AB  - INTRODUCTION: This was a descriptive non-interventional study in HIV-1-infected
      patients treated with DRV/r conducted in the clinical setting, with a single-arm
      prospective design. The primary objective was to collect data on utilization of
      darunavir/ritonavir (DRV/r) under the conditions described in the marketing
      authorization. Efficacy (measured as viral load [VL] <50 copies/mL and CD4+ cell
      count) was evaluated for DRV/r in combination with other antiretroviral (ARV)
      agents in routine clinical practice in Italy. MATERIALS AND METHODS: Here we
      describe an analysis of effectiveness and durability data from two cohorts of
      DRV/r-experienced patients with HIV-1 infection, already receiving DRV/r
      according to usual clinical practice, collected prospectively from June 2009 to
      December 2012: Cohort 1, data from patients from the DRV/r Early Access Program
      (TMC114-C226 study; N=235 patients) and Cohort 2, a separate cohort of ARV-DRV/r
      experienced patients (N=407 patients), treated with DRV/r in the market. Patient
      characteristics are shown in Table 1. RESULTS: The median length of DRV/r
      exposure during the study was 925 days (interquartile range [IQR] 692-1006) in
      Cohort 1, and 581 (IQR 508-734) days in Cohort 2. Of those patients that
      completed the study, 94% and 87% of patients were virologically suppressed in
      Cohort 1 and 2, respectively, at last study visit (LSV). As expected, the
      virological suppression rate was higher in patients with baseline VL <50
      copies/mL (Table 2). Mean CD4+ cell counts improved from baseline to LSV in both
      cohorts (Cohort 1: +54 cells/uL [95% CI 31, 77] and Cohort 2: +59 cells/uL [95%
      CI 44, 73]). High persistence rates were seen in both cohorts, with 75.3% of
      patients in Cohort 1 and 82.6% in Cohort 2 remaining on treatment at LSV; very
      few patients discontinued due to virologic failure (Table 1). Other reasons for
      study discontinuation are shown in Table1. Very few patients changed DRV/r dosing
      during the study, 15 from 1200 to 800 mg o.d. CONCLUSIONS: In patients already
      treated with DRV/r, DRV/r-based ARV treatment provided effective viral
      suppression with long-lasting durability, low virological response failure, low
      discontinuation rates and good tolerability. These data confirm DRV/r to be an
      effective treatment choice in previously treated patients.

PMID- 25397531
TI  - Efficacy of a dual therapy based on darunavir/ritonavir and etravirine in ART
      experienced patients.
AB  - INTRODUCTION: Nucleoside reverse transcriptase inhibitors (NRTI)-sparing regimens
      have been studied in antiretroviral therapy (ART)-naive patients but data with
      ART-experienced are scarce. NRTI-sparing regimens may be an option in patients
      with toxicities and for simplification reasons. METHODS: Retrospective
      multicentre analysis including ART-experienced patients starting treatment with
      darunavir/ritonavir and etravirine (DRV/r 800 mg/100 mg QD or 600 mg/100 mg BID
      and ETV 400 mg QD or 200 mg BID) with at least six months of follow-up. Primary
      endpoint was proportion of patients with VL<50 copies/mL at 48 weeks with an ITT
      analysis (missing or switch equals failure). Secondary endpoints were safety, CD4
      count and lipid changes over 48 weeks. RESULTS: Seventy-five patients were
      included of whom 44 (58.6%) had HIV RNA<50 copies/mL. Baseline characteristics:
      median age 50 years (IQR 34-65), 72% males, 93% Caucasians, 38.6% hepatitis C,
      and 45.4% with CDC C stage. Median HIV duration and time on ART were 20 (IQR 7
      28) and 14 years (IQR 5-21) respectively. Reasons for switching were virologic
      failure in 27 (36%), simplification in 25 (33.3%), toxicity in 20 (26.6%) and
      other 3 (4.1%). Most of them received DRV/r and ETV QD. Thirty-nine patients had
      NNRTI resistance mutations [28 K103N (37.3%), 6 Y181I/C (8%), 3 G190A (4%)] and
      29 patients had >=1 primary PI mutations. Main analysis (ITT) showed that 67
      (89.3%) had a VL undetectable at 24 weeks (95% CI 83.1-95.5) and 57 (76%) at 48
      weeks (95% CI 68.4-83.6). On treatment analysis showed that 94.3% and 89% had a
      viral load<50 copies at 24 and 48 weeks, respectively. 11 (14.6%) patients
      discontinued the regimen (three virologic failures, three switching to
      darunavir/ritonavir monotherapy, two to salvage regimen and three due to
      toxicity). No significant changes in CD4+ count and lipid changes were observed
      at 48 weeks. CONCLUSIONS: Dual therapy with Darunavir/ritonavir and etravirine is
      an efficacious and safety option in ART-experienced HIV patients even in patients
      on virologic failure.

PMID- 25397532
TI  - Efficacy of PI monotherapy versus triple therapy for 1964 patients in 10
      randomised trials.
AB  - INTRODUCTION: The efficacy of protease inhibitor monotherapy has been analyzed
      with different endpoints: initial HIV-1 RNA rebound, long-term HIV-1 RNA
      suppression after re-intensification, treatment-emergent drug resistance,
      neurocognitive testing and HIV-1 RNA in the cerebrospinal fluid (CSF). METHODS: A
      PUBMED search identified nine randomised trials of PI monotherapy versus triple
      therapy in patients with HIV RNA<50 copies/mL at baseline. RESULTS from the
      recently completed PROTEA trial were also included. The percentage of patients
      with HIV RNA suppression <50 copies/mL was analyzed using switch equals failure
      and intensification included endpoints (ITT). The number of patients with new
      drug resistance mutations, HIV RNA in the CSF or change in neurocognitive
      function was analyzed by treatment arm. RESULTS: Four trials evaluated
      darunavir/r monotherapy (n=785: MONET, MONOI, MONARCH, PROTEA), five evaluated
      lopinavir/r monotherapy (n=592: OK-04, KalMo, KALESOLO, KRETA, MOST) and one
      evaluated both (MRC PIVOT, n=587). HIV-1 RNA suppression rates tended to be lower
      on PI monotherapy than triple therapy in "switch equals failure" analysis (76% vs
      82%), but not when the outcome of intensification was included (87% vs 85%).
      There were small numbers of patients taking PI monotherapy with detectable HIV-1
      RNA in the CSF, in three trials: PROTEA (n=2), MONOI (n=2) and MOST (n=5), but
      only two cases of CSF viral escape (MONOI). In two trials, there was no
      difference in neurocognitive test results between PI monotherapy and triple
      therapy, based on z-scores from five domains (in PROTEA, mean change in NPZ-5
      score=0.0 for DRV/r monotherapy vs -0.10 for triple therapy); similar results
      were observed in the MRC PIVOT trial. The risk of treatment emergent NRTI or PI
      resistance (Table 1) was 11/973 (1.1%) for patients on PI monotherapy, versus
      7/991 (0.7%) for patients on triple therapy. CONCLUSIONS: In 10 randomised trials
      of 1964 patients with HIV-1 RNA suppression at baseline, PI monotherapy showed a
      higher risk of HIV RNA elevations, and small numbers with HIV RNA detectable in
      CSF and concomitantly in the plasma. However there was no increased risk of
      treatment-emergent drug resistance, neurocognitive endpoints were not different
      between the arms and HIV-1 RNA suppression rates after intensification were
      similar between PI monotherapy and triple therapy.

PMID- 25397533
TI  - The efficacy, pharmacokinetics, safety and cardiovascular risks of switching
      nevirapine to rilpivirine in HIV-1 patients: the RPV switch study.
AB  - INTRODUCTION: Nevirapine (NVP) induces cytochrome P450 3A4 by which rilpivirine
      (RPV) is metabolized. Switching NVP to RPV could result in decreased RPV exposure
      with subsequent virological failure and dyslipidemia because NVP is regarded as
      the least dyslipidemic, non-nucleoside, reverse transcriptase inhibitor. This
      trial evaluated the efficacy, pharmacokinetics, safety and cardiovascular risks
      of switching NVP to RPV. MATERIALS AND METHODS: Prospective open label controlled
      trial. HIV-1 patients with HIV-1 RNA <50 copies/mL on once daily NVP,
      emtricitabine/tenofovir (FTC/TDF) switched to single tablet RPV/FTC/TDF. Eligible
      patients on NVP, FTC/TDF were controls. Primary endpoint was week 12 HIV-1 RNA
      <50 copies/mL by intention to treat analysis. Secondary endpoints were week 24
      HIV-1 RNA <50 copies/mL, NVP and RPV pharmacokinetics, safety and fasting lipids,
      Framingham risk scores (FRS) and Adult Treatment Panel III (ATP-III) lipid goals.
      RESULTS: Of 189 eligible patients, we included 50 RPV switchers and 139 NVP
      controls. Week 12 HIV-RNA was <50 copies/mL in 46/50 switchers (92.0%) which was
      not different from the hypothesized 90% week 12 suppression rate (p=.431). Forty
      four of 50 switchers had week 24 HIV-1 RNA <50 copies/mL compared to 126/139
      controls (difference: 2.6%, 95% CI -7.6% to 12.8%, p=.593). NVP plasma
      concentrations were below detection level in all at week 3. Mean week 1 RPV
      trough concentration was 0.083 mg/L and comparable to phase III trial data
      (p=0.747). Adverse events occurred in 36 switchers, the majority (82.0%) were
      grade one. Two switchers discontinued RPV for side effects. Significant changes
      over 24 weeks (p<0.001) were observed in switchers on total cholesterol (TC, 
      0.67 mmol/L, 95% CI -0.50 to 0.83), low density lipoprotein (LDL)-C (-0.36, 95%
      CI -0.21 to -0.51) and high density lipoprotein (HDL)-C (-0.28, 95% CI -0.20 to 
      0.35). The TC/HDL-C ratio increased 0.20 (95% CI 0.02 to 0.37; p=.029) and
      systolic blood pressure decreased 6.0 mmHg (95% CI -1.7 to -10.3; p=.007). The
      median FRS did not change over 24 weeks (8.4% vs. 7.7%; p=.119). More patients
      achieved LDL-C (+15%; p=.016) and TC (+25%; p<0.001) ATP-III treatment goals at
      week 24 on RPV. CONCLUSIONS: A NVP to RPV switch does not influence RPV exposure
      and results in adequate ongoing HIV-1 suppression. RPV could be an option for
      patients at risk for cardiovascular diseases.

PMID- 25397534
TI  - Time on drug analysis based on real life data.
AB  - INTRODUCTION: The health condition of HIV-1 infected patients has improved during
      the last years, but lifelong antiretroviral treatment is still needed. However
      resistance, multiple side effects and drug to drug interactions of
      antiretrovirals challenge the establishment of a long lasting regimen. The
      average running time of each antiretroviral drug composing the therapy episodes
      combination antiretroviral therapy (cART) may be seen as an indicator of
      effectiveness and tolerability. MATERIALS AND METHODS: To evaluate the running
      time of each drug used in HIV-1 treatment, we extracted therapy episodes from the
      latest release of the EuResist database (www.euresist.org). The evaluation period
      was from Oct 2006 to Oct 2012. Inclusion criteria for this analysis were
      continuous patient monitoring for at least two years (i.e. latest therapy start
      in Oct 2010), and the extraction of at least 100 cases per drug analyzed. Drug
      intake interruptions of less than a month were ignored. RESULTS: At the time of
      data extraction (Feb 2013), the EuResist database contained data from 61,953
      patients of which 11,499 fulfilled the inclusion criteria. We obtained 37,035
      drug treatment lines from 38,153 cARTs and the overall average length of drug
      intake was 18.7 months. For each single drug these average durations measured in
      months were: 18.3 (3TC); 20.8 (ABC); 12.3 (d4T); 14.3 (ddI); 23.2 (FTC); 23.0
      (TDF); 13.4 (ZDV); 19.8 (EFV); 21.9 (ETR); 17.7 (NVP); 19.2 (ATV); 22.7 (DRV);
      18.7 (FPV); 17.9 (LPV); 15.2 (SQV); 14.6 (TPV); 22.6 (RAL); 21.9 (MVC) and 8.9
      (T20). Overall drug discontinuation rates at one, two and three years were 35.0,
      48.8 and 95.8%, respectively. Average discontinuation rates for the different
      drug classes at two years these were: 46.2% for NRTIs; 49.7% for NNRTIs; 55.4%
      for PIs and 37.6% for Raltegravir/Maraviroc. CONCLUSIONS: In this cohort the
      overall frequency of therapy changes is high. After two years of treatment, on
      average 49% of the patients change at least one drug in their cART. Thus, we have
      to expect numerous changes in the long term perspective of treatments. The
      observed differences in durations suggest that newer drugs might have advantages
      over older ones. However possible reasons and confounding factors (such as number
      of past treatment lines, co-medication, risk group, etc.) were not addressed at
      this time of the analysis.

PMID- 25397535
TI  - Switch to raltegravir-based regimens and HIV DNA decrease in patients with
      suppressed HIV RNA.
AB  - INTRODUCTION: Raltegravir intensification is associated with an increase in 2-LTR
      episomal HIV DNA= circles, indicating a persistent low-level replication, in some
      individuals in ART with suppressed HIV RNA. We aimed at monitoring residual
      plasma HIV RNA and cellular HIV DNA in virologically suppressed patients
      switching to a raltegravir-based regimen. MATERIALS AND METHODS: Forty-six HIV
      infected subjects on PI or NNRTI based-regimens, with plasma HIV RNA level <40
      copies/mL for >=6 months and CD4 >200 cells/uL for >=12 months were enrolled.
      Thirty-four patients switched to raltegravir-based regimen (RASTA study group)
      and 12 continued a PI or NNRTI based-regimen (control group). Ultrasensitive HIV
      residual viremia and total PBMC HIV DNA were assessed at baseline (W0), 24 (W24)
      and 48 (W48) weeks. HIV RNA levels were determined by an ultrasensitive test
      derived from a commercial real time PCR (limit of detection 5 copies/ml). A real
      time PCR was used to quantify HIV DNA copy numbers in PBMCs. RESULTS: At W0, HIV
      DNA was detected in all patients while at W48 it was detectable in 82.3% of RASTA
      group vs 100% of controls (p=0.01). The difference between the average values of
      HIV DNA log10 copies/10 degrees 6 CD4 at W0 (median 3.11, IQR 2.70-3.45) and W48
      (median 2.87, IQR 2.24-3.38) was statistically significant for RASTA group
      (p=0.035). Male gender (mean difference -0.37 log10 copies/10 degrees 6 PBMC,
      p=0.023) and previous PI based-ART (mean difference +0.39 log10 copies/10 degrees
      6 PBMC, p=0.036) were predictive of HIV DNA level at W0. After adjusting for
      previous PI based-ART, male gender was the only variable independently associated
      with HIV DNA size at W0 (mean difference -0.326 log10 copies/10 degrees 6 PBMC,
      95% CI -0.641, -0.011 p=0.043). Ultrasensitive HIV-1 RNA was detectable at W0 in
      50% of RASTA group versus 66.7% of controls and at W48 in 32.4% versus 45.5%,
      respectively. No differences were found between HIV RNA levels at W0 and W48
      within and between the two groups. CONCLUSIONS: Switching to raltegravir-based
      regimens may be associated with a decrease of HIV reservoir, as measured by total
      PBMC HIV DNA. A larger sample size is required to confirm this finding.

PMID- 25397536
TI  - Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line
      regimen in an urban clinic in Kampala.
AB  - INTRODUCTION: In 2011 Uganda recommended boosted atazanavir (ATV/r) as the
      preferred PI for second line due to once daily dosing, replacing aluvia (LPV/r)
      (1, 2). The evidence was based on the BMS O45 trial, of LPV/r vs ATV/r was
      performed in a high-income setting, on patients with prior PI use and resistance
      testing (2, 3). There are no RCTs or observational studies comparing use of ATV/r
      with LPV/r in patients failing NNRTI first line antiretroviral therapy in sub
      Saharan Africa (3, 4). The Infectious Diseases Institute (IDI) has a large second
      line cohort (>1838). This aims to compare clinical, immunologic and virologic
      response of LPV/r versus ATV/r at IDI. METHODS: Retrospective cohort analysis on
      routinely collected data of patients switched to second line with NRTI backbones
      TDF/3TC or FTC, AZT/3TC, ABC/3TC from January 2009 to December 2013. Students T
      tests and Chi-square tests were used in this analysis. RESULTS: A total of 1286
      (73.5% female) patients were switched to LPV/r 991 (77%) and ATV/r 295 (23%)
      (p<0.001). NRTI backbones were 760 on TDF/3TC (66.8% LPV/r vs 33.2% on ATV/r),
      504 on AZT/3TC (93.3% vs 6.7%), and 22 on ABC/3TC (59% vs 41%). Median (IQR) time
      on first line for LPV/r was 21 (1-44) months and for ATV/r was 41 months (22-68).
      Median CD4 (IQR) at switch to LPV/r was 181 cells/uL (66-424) and to ATV/r was
      122 (57-238) (p<=0.001). A total of 366 patients had CD4 done at six months after
      switch and the mean (IQR) CD4 increase was 153 (54-241) for LPV/r versus 116 (52
      171) for ATV/r (p=0.232). Additionally, 304 had a CD4 at 12 months and the means
      were 172 (45-272) for LPV/r vs 179 (60-271) for ATV/r (p=0.426). There was no
      significant difference in the mean increment by NRTI backbone or by stratifying
      to viral load (VL) at time of switch to VL <100,000 and >=100,000. Median (IQR)
      VL at switch was 61,000 (13,000-2,030,000) LPV/r and 51,000 (14,000_151,000)
      ATV/r. 269 had a VL done in the first 12 months and 178/250 (71.2%) on LPV/r
      versus 16/19 (84.2%) on ATV/r were undetectable (p=0.228). 259 (26%) LPV/r versus
      33(11%) ATV/r had >=1 opportunistic infections on second line (p<0.001).
      CONCLUSIONS: This is an observational study based on our experience at IDI. Like
      elsewhere in Africa, there is no routine viral load testing, making it difficult
      to get sensitive analysis of data on ART efficacy within routine clinical
      practice. Nevertheless, this observational study is reassuring in terms of
      efficacy of both ATV/r and LPV/r for patients failing first line therapy in our
      setting.

PMID- 25397537
TI  - Switch to Stribild versus continuation of NVP or RPV with FTC and TDF in
      virologically suppressed HIV adults: a STRATEGY-NNRTI subgroup analysis.
AB  - INTRODUCTION: Switch to Stribild (STB) was non-inferior to continuation of a non
      nucleoside reverse transcriptase inhibitor (NNRTI) with emtricitabine and
      tenofovir DF (FTC/TDF) at week 48 in virologically suppressed HIV adults (1). We
      report the Week 48 efficacy and safety of STB versus nevirapine (NVP) or
      rilpivirine (RPV) with FTC/TDF in suppressed subjects. MATERIALS AND METHODS:
      Virologically suppressed subjects on an NNRTI with FTC/TDF regimens for >=6
      months were randomized (2:1) to switch to STB versus continue their NNRTI
      regimen. Eligibility criteria included no documented resistance to FTC and TDF,
      no history of virologic failure and eGFR >=70 mL/min. The primary endpoint was
      the proportion of subjects in the modified ITT population who maintained HIV-1
      RNA <50 copies(c)/mL at Week 48 by FDA snapshot algorithm (12% non-inferiority
      margin). Subgroup analysis by non-EFV NNRTI use (NVP [74]; RPV [19]; etravirine
      [3]) at screening was pre-specified. RESULTS: The mITT population included 433
      subjects who were randomized and treated. In the non-EFV NNRTI subgroup, 59
      switched to STB; 37 continued a non-EFV NNRTI (27 NVP, 10 RPV) with FTC/TDF. At
      week 48, 97% STB versus 95% non-EFV NNRTI maintained HIV-1 RNA <50 c/mL. No
      emergent resistance was detected in either group. No difference in median
      increases from baseline in CD4 count at week 48 (cells/uL): 25 STB versus 55 non
      EFV NNRTI (p=0.78). No discontinuation due to adverse events; no cases of
      proximal renal tubulopathy. As expected, there were no significant changes in the
      frequency of neuropsychiatric symptoms (i.e. anxiety, insomnia, dizziness, vivid
      dreams, weird/intense dreams, and nightmares) reported on the HIV Symptom Index
      at week 48 compared to baseline after switching to STB. There was a greater but
      non-progressive decrease from baseline in eGFR in the STB versus non-EFV NNRTI
      group; median changes (mL/min) at week 48: -9.1 versus -1.4. Switch to STB was
      associated with a higher treatment ease (convenience, flexibility, demand,
      lifestyle, understanding) score (range: -15 to 15) at week 4 (median: 14 vs 11;
      p=0.047) and week 24 (median: 14 vs 12.5; p=0.038). CONCLUSIONS: In this small
      group of virologically suppressed subjects, switch to STB vs continuation of NVP
      or RPV with FTC/TDF was safe, well-tolerated, and associated with a high rate of
      virologic suppression at week 48. There was more treatment ease with STB use.

PMID- 25397538
TI  - Switching to nevirapine-based regimens after undetectable viral load is not
      associated with increased risk of discontinuation due to toxicity.
AB  - INTRODUCTION: Due to its good tolerability, favourable cardiovascular risk
      profile, low-pill burden and cost, nevirapine-based regimens are an attractive
      simplification strategy for patients with suppressed viral load (VL). However,
      current guidelines recommend caution if nevirapine (NVP) is prescribed in males
      and females with CD4 counts above 400 or 250 cells/uL, respectively. The aim of
      this study is to determine the prevalence and risk factors associated with
      development of toxicity or treatment discontinuation in patients switching to NVP
      based regimens. MATERIALS AND METHODS: Retrospective chart review of HIV-infected
      patients with suppressed VL who switched from a PI-based regimen to a NVP-based
      regimen in four HIV clinics in Argentina, between 1997 and 2013. Bivariate and
      multivariate analyses were performed to explore factors associated with treatment
      discontinuation. High CD4 count was defined as CD4-cell count >=400 or 250
      cells/uL in males and females, respectively. RESULTS: Of 218 patients included,
      165 (75.7%) were male; 21 (9.6%) were co-infected with HCV and/or HBV. Median
      baseline (BSL) CD4 count: 138 cells/uL (IQR: 64-276). At switch, patients had a
      median age of 38 years (IQR: 33.4-43.8) and had been suppressed for a median of
      1.4 years (IQR: 0.6-2.2); 138 patients (63.3%) had high CD4-cell counts: among
      females, median CD4 count at switch was 462 (IQR: 330-709) cells/uL; among males,
      433 (IQR: 305-595) cells/uL. Thirty-six patients (13.5%) presented NVP-related
      toxicity (30 skin toxicity, 6 hepatic toxicity), 29 (13.3%) discontinued NVP.
      Median time to development to toxicity: 32 days (IQR: 15-75). In bivariate
      analysis, chronic hepatitis was the only variable associated with development of
      toxicity (OR: 2.90, 95% CI 1.08-7.78). In multivariate analysis, no statistical
      significant associations were observed between either development of toxicity or
      treatment discontinuation and gender, chronic hepatitis, age or CD4-cell count at
      BSL or at switch (all p>0.05). CONCLUSIONS: In our study, switching to a NVP
      based regimen in patients with undetectable VL was associated with a low
      incidence of skin or liver toxicity, and treatment discontinuation. Moreover,
      these were unrelated to the CD4-cell count. Our findings suggest that, in
      contrast with ART-naive patients, switching to NVP-based regimens could be a safe
      strategy for patients with suppressed viremia regardless of the CD4-cell count.

PMID- 25397539
TI  - Lipid changes in HIV-patients switching to the coformulated single tablet
      FTC/RPV/TDF (Eviplera(r)). Efficacy and safety analysis. GeSida Study 8114.
AB  - INTRODUCTION: Rilpivirine (RPV) has a better lipid profile than efavirenz (EFV)
      in naive patients (1). Switching to RPV may be convenient for many patients,
      while maintaining a good immunovirological control (2). The aim of this study was
      to analyze lipid changes in HIV-patients at 24 weeks after switching to
      Eviplera(r) (emtricitabine/RPV/tenofovir disoproxil fumarate [FTC/RPV/TDF]).
      MATERIALS AND METHODS: Retrospective, multicentre study of a cohort of
      asymptomatic HIV-patients who switched from a regimen based on 2 nucleoside
      reverse transcriptase inhibitors (NRTI)+protease inhibitor (PI)/non nucleoside
      reverse transcriptase inhibitor (NNRTI) or ritonavir boosted PI monotherapy to
      Eviplera(r) during February-December, 2013; all had undetectable HIV viral load
      for >=3 months prior to switching. Patients with previous failures on
      antiretroviral therapy (ART) including TDF and/or FTC/3TC, with genotype tests
      showing resistance to components of Eviplera(r), or who had changed the third
      drug of the ART during the study period were excluded. Changes in lipid profile
      and cardiovascular risk (CVR), and efficacy and safety at 24 weeks were analyzed.
      RESULTS: Among 305 patients included in the study, 298 were analyzed (7 cases
      were excluded due to lack of data). Men 81.2%, mean age 44.5 years, 75.8% of HIV
      sexually transmitted. 233 (78.2%) patients switched from a regimen based on 2
      NRTI+NNRTI (90.5% EFV/FTC/TDF). The most frequent reasons for switching were
      central nervous system (CNS) adverse events (31.0%), convenience (27.6%) and
      metabolic disorders (23.2%). At this time, 293 patients have reached 24 weeks:
      281 (95.9%) have continued Eviplera(r), 6 stopped it (3 adverse events, 2
      virologic failures, 1 discontinuation) and 6 have been lost to follow up. Lipid
      profiles of 283 cases were available at 24 weeks and mean (mg/dL) baseline vs 24
      weeks are: total cholesterol (193 vs 169; p=0.0001), HDL-c (49 vs 45; p=0.0001),
      LDL-c (114 vs 103; p=0.001), tryglycerides (158 vs 115; p=0.0001), total
      cholesterol to HDL-c ratio (4.2 vs 4.1; p=0.3). CVR decreased (8.7 vs 7.5%; p=
      0.0001). CD4 counts were similar to baseline (653 vs 674 cells/uL; p=0.08), and
      274 (96.8%) patients maintained viral suppression. CONCLUSIONS: At 24 weeks after
      switching to Eviplera(r), lipid profile and CVR improved while maintaining a good
      immunovirological control. Most subjects switched to Eviplera(r) from a regimen
      based on NNRTI, mainly EFV/FTC/TDF. CNS adverse events, convenience and metabolic
      disorders were the most frequent reasons for switching.

PMID- 25397540
TI  - Efficacy and safety of rilpivirine-based regimens in treatment-experienced HIV-1
      infected patients: a prospective cohort study.
AB  - INTRODUCTION: Rilpivirine (RPV) is a new once-daily, non-nucleoside, reverse
      transcriptase inhibitor (NNRTI). In treatment-naive patients, RPV has shown non
      inferior antiviral activity to efavirenz but data in treatment-experienced
      patients are more limited. We assessed the efficacy and safety of RPV in
      treatment-experienced patients switching to a RPV-based regimen. METHODS: Between
      September 2012 and June 2013, all antiretroviral therapy (ART) experienced HIV-1
      infected patients with a plasma HIV-RNA level <50 cp/mL, and switching to a RPV
      based regimen, were enrolled in this prospective monocentric cohort study.
      Clinical and laboratory data were collected every 3 months to assess safety and
      efficacy. The primary endpoint was the proportion of patients with virologic
      success (HIV-RNA load <50 cp/mL) at 12 months using the FDA snapshot algorithm.
      RESULTS: A total of 281 patients (76% male, median age: 47 years, 56% MSM) were
      enrolled in this study. Median lymphocyte CD4 count at baseline was 640/mm(3).
      Patients have received ART for a median of 7 years and viral replication was
      fully suppressed for a median of 3 years. Before the switch, 39% patients were
      treated with NNRTI, 52% with protease inhibitor and 7% with integrase inhibitor
      based regimens. Reasons for switch were simplification (176 cases), adverse
      events (AEs) (93 cases) and others (12 cases). At month 12 (database frozen on
      June 2014) in the snapshot analysis, 56% of patients met virologic success, 5%
      experienced virologic failure (n=14) and 39% had no data in the window period. In
      the LOCF analysis (using data from the previous available visit before month 12),
      89% patients were suppressed, 5% had virologic failure and 6% had no data.
      Genotypic resistance analysis was performed in 7/14 patients at the time of
      virologic failure (3 of whom had previous NRTI/NNRTI resistance-associated
      mutations (RAMs)), and new NNRTI and NRTI RAMs emerged in 4 patients. RPV-based
      regimen was generally well tolerated and only 6% of patients discontinued
      treatment for AEs. Grade 2-4 treatment-related AEs occurred in 39 patients: 6 had
      rashes, 13 neuropsychiatric symptoms, 10 GI symptoms, 10 biological
      abnormalities. At month 12, significant changes from baseline were seen for total
      and LDL cholesterol (-0.5 and -0.28 mmol/L, respectively, p<0.05 for both), and
      plasma creatinine (+5.8 umol/L, p<10-4). CONCLUSIONS: In patients fully
      suppressed on ART, switching to a RPV-based regimen in clinical practice was well
      tolerated and associated with few virologic failures.

PMID- 25397541
TI  - Durability of first antiretroviral treatment in HIV chronically infected
      patients: why change and what are the outcomes?
AB  - INTRODUCTION: First antiretroviral therapy (ART) is often switched to simpler,
      more potent or better tolerated regimens (1, 2). Although discontinuation rates
      are frequently studied, the durability of regimens is rarely approached.
      MATERIALS AND METHODS: Retrospective study with the following objectives: analyze
      first ART schemes and their durability in naive patients with chronic HIV-1 and 2
      infections, evaluate factors influencing ART change, second-line ART and
      consequent virologic and immunologic responses. Patients had follow-ups in a
      Central University Hospital, started ART between January 2007 and December 2012
      and changed first regimens. Clinical data was obtained from medical records and
      analyzed using the Statistical Package for the Social Sciences (version 20).
      RESULTS: Of the 652 naive patients who started ART, 164 changed regimens. The
      majority had HIV-1 infection (n=158). The mean age was 43.9 years (standard
      deviation+/-14.3), with a male predominance of 57.9%. Regimens with efavirenz
      were the most common amongst HIV-1 patients (50%) followed by lopinavir/r (22%).
      In HIV-2 patients, lopinavir/r (n=3) regimens were most prevalent. First ART
      regimens had a mean duration of 12.1 months. There was no difference between
      NNRTI (59.8%) and protease inhibitor (40.2%) schemes regarding durability.
      Adverse reactions were the major cause of ART switching (55.5%) followed by
      therapy resistance (12.1%). Age was inversely related to durability (p=0.007 Mann
      Whitney, Phi coefficient -0.161) and associated with the appearance of adverse
      reactions (p=0.04, Chi-square). Younger patients had a reduced risk of adverse
      reactions by 27%. Adverse reactions increased the risk of inferior durability by
      40%. Psychiatric symptoms (28.4%) were the most prevalent, all attributed to
      efavirenz. The year of ART initiation was associated with different durability
      rates (p=0.005, Mann-Whitney). Patients started on ART before the year 2010
      reduced the probability of inferior ART duration by 25.8%. After second-line ART
      regimens, TCD4+ counts>500 cell/uL were increased by 38% and favourable virologic
      outcome achieved in 84%. CONCLUSIONS: Adverse reactions were the main cause for
      ART switching, supporting a cautious approach when initiating regimens,
      particularly in older patients. All ART naive patients who changed initial
      therapy had favourable immunological and virologic responses.

PMID- 25397542
TI  - Switching from an EFV-based STR to a RPV-based STR is effective, safe and
      improves HIV patients health status.
AB  - INTRODUCTION: TDF/FTC/RPV has been shown effective in both naive and PI-pre
      treated patients. Less is known about a switch strategy in subjects receiving
      EFV. MATERIALS AND METHODS: We evaluated viro-immunologic outcomes, Quality of
      Life (QoL) and costs of an unselected cohort of patients switching from a
      TDF/FTC/EFV STR (>=6 months duration) to a TDF/FTC/RPV STR. The considered
      outcome measures were quality-adjusted life years (QALYs) as measured with the
      EQ5D questionnaire and the overall direct health costs. 64 patients with a
      baseline viral load<50 copies/mL were randomized to immediately switch therapy or
      to continue TDF/FTC/EFV for four months and then switch to TDF/FTC/RPV. Six
      patients in the deferred switch group did not actually change cART. RESULTS:
      Patients were mostly males (73.4%) with a mean age of 46 years, a baseline mean
      HIV-RNA of 6.4 copies/mL and a mean baseline CD4 count of 588 cells/uL. For the
      considered follow-up period, the mean cost per patient resulted 2,563 for
      TDF/FTC/RPV and 2,572 for TDF/FTC/EFV. Viremia remained undetectable and CD4
      stable in all patients. Over time the mean QoL increased in the RPV arm ad
      slightly decreased in the EFV arm, after four months the mean per patient QALYs
      was 0.849 for RPV and 0.841 for EFV, respectively (Figure 1). A sharp increment
      of QoL was observed in the deferred-switch arm after switch, too. VAS analysis of
      health status perception also increased overall from 82.78 to 83.79 due to the
      improvement in the RPV arm. Mean cholesterol levels improved in the RPV arm from
      203 to 170 mg/dL, while an increment from 190 to 207 mg/dL was observed in the
      EFV arm. HDL levels lowered from 49 to 45 and rose from 53 to 54 mg/dL in the RPV
      and EFV arms, respectively. Triglycerides levels improved both in the RPV arm
      (from 138 to 112 mg/dL) and in the EFV arm (from 110 to 103 mg/dL). CONCLUSIONS:
      Switching from TDF/FTC/EFV to TDF/FTC/RPV is a safe, well tolerated strategy that
      improves the overall health status of HIV-treated patients. The switch does not
      expose patients to a risk of virologic failure due to possible PK interactions of
      the drugs. RPV compared to EFV proved to be cost-effective showing lower cost and
      higher outcome measure values.

PMID- 25397543
TI  - Durability of lopinavir/ritonavir dual-therapies in individuals with viral load
      <50 copies/mL in the observational setting.
AB  - INTRODUCTION: We aimed at evaluating the efficacy and durability of a
      lopinavir/ritonavir-based dual regimen (LPV/r-DR) in virologically controlled HIV
      infected individuals in current clinical practice. METHODS: Patients who have
      initiated for the first time a LPV/r-DR with HIV-RNA<50 copies/mL were included
      in this observational study. The main endpoints were: time to virological rebound
      [VR=time of first of two consecutive viral loads (VL)>50 copies/mL] and time to
      experience either a single VL>200 copies/mL or discontinuation/intensification (=
      treatment failure, TF). Individuals' follow-up accrued from the date of starting
      the LPV/r-DR to event or last available VL. Kaplan-Meier curves and Cox
      regression analysis were used. Covariates included in the multivariable analysis
      were gender, age, route of transmission, hepatitis co-infection, calendar year of
      starting the DR, nadir CD4+ count, VL at initiation of first cART, previous
      failures to protease inhibitors (PIs), time with undetectable VL before starting
      the DR and the type of DR [nucleoside reverse transcriptase (NRTI), non-NRTI
      (NNRTI), raltegravir or maraviroc, with NRTI as reference group]. RESULTS are
      presented as median (Q1, Q3) or frequency (%) as appropriate. RESULTS: 108
      individuals followed for 18 (7, 30) months were included; baseline (BL)
      characteristics are detailed in Table 1. CONCLUSIONS: A LPV/r-DR can be
      considered a valuable option in patients with HIV-RNA<50 copies/mL and ongoing
      toxicity from the third drug of the regimen, although up to 17% of patients
      showed viral rebound by 3 years. Older patients are at lower risk of failure with
      this strategy, but larger sample size is needed to identify who might benefit
      from this strategy instead of others.

PMID- 25397544
TI  - Use of maraviroc in patients with undetectable viral load: efficacy, tolerance
      and predictors of viral response in MARAVIROC-cohort study.
AB  - INTRODUCTION: No controlled clinical trials had studied the role of maraviroc
      (MRV) in fully suppressed patients (1). MATERIALS AND METHODS: MRV-cohort is an
      observational, retrospective, multicentric (27 sites) large cohort study of
      patients starting MRV in clinical practice under different circumstances, with at
      least 48 weeks of follow-up. For the present analysis we selected all those
      patients starting with an HIV-RNA<50 copies/mL. Demographics, baseline CD4 cell
      count, past history of antiretroviral treatment (ART), tropism, reasons for MRV
      use, MRV based therapy and change/end of MRV use were assessed. Paired analysis
      of lipid, hepatic and kidney profile changes and univariate and multivariate
      analyses of HIV-RNA<50 copies/mL at 48 weeks were explored. RESULTS: We included
      247 out of 667 subjects from the entire cohort. At study entry, their median age
      was 47 years, 23% were women, 31% MSM, 49% had CDC category C, median CD4+ counts
      were 468 cells/mm(3), 46% were HCV+ and 4.5% AgHBs+. Tropism information was
      available in 197 (94% R5). Median length of prior ARTV was 10.7 years, with
      exposure to a median of three drug families. Main reasons for prescribing MRV
      were: toxicity 38%, inmunodiscordance 23%, simplification 19% and admission in a
      clinical trial 10.4%. MRV based therapies used were MRV+2NRTIs 9%, MRV+PI 46%,
      MRV+PI+other 40% and MRV+other 5%. At 48 weeks, 23% of patients had changed or
      finished MRV therapy due to toxicity 2.4%, virological failure 2%, immunological
      failure 1.2%, simplification 3,2%, trial requirement 9.7%, medical decision 2.8%,
      treatment suspension 1.2% and unknown 0.4%. At 48 weeks, no significant changes
      were observed in lipid, hepatic or kidney profiles, and 85% of patients remained
      with HIV-RNA<50 copies/mL. Focusing on viral response univariate and multivariate
      models did not show any significant baseline variable explaining viral failure.
      CONCLUSIONS: In clinical practice MRV was used, mostly in R5 positive patients,
      with adequate efficacy and tolerance, but important number of patients changed
      due to non-clinical reasons. In this scenario neither reason for use of MRV nor
      MRV-based therapy explained viral failure.

PMID- 25397545
TI  - Lamivudine plus darunavir boosted with ritonavir as simplification dual regimen
      in HIV-infected patients.
AB  - INTRODUCTION: The combination of lamivudine plus a protease inhibitor boosted
      with ritonavir (PI/r) has become an alternative as simplification strategy in HIV
      infected patients with toxicity/intolerance to other nucleoside analogues (NA).
      Lamivudine plus darunavir/r (DRV/r) could be an adequate once daily option.
      MATERIALS AND METHODS: Prospective cohort study of 48 HIV-infected patients on
      suppressive triple therapy-based HAART, HBV negative, who switched to lamivudine
      300 mg plus DRV/r 800/100 mg once daily. RESULTS: Mean age was 50 yrs (35-74),
      and 65% were male. Thirty patients (63%) had HCV co-infection (fibrosis 4 in 7
      cases, 23%). Median time of HIV infection was 19.1 years, and CD4+ count nadir
      was 220 cells/uL (2-604). They had received a mean of three regimens before (2
      20), and 20 (42%) had a previous AIDS diagnosis. In eight cases, a previous
      resistance test showed two to seven secondary mutations in the protease gene,
      without resistance to DRV/r (one patient with the I84V mutation). At baseline,
      patients had viral suppression (<50 copies/mL) for a median time of 1263 days
      (341-1884), and they were receiving predominantly a PI based regimen (ATV in
      four, FPV in four, LPV in three, DRV in six) or an efavirenz-based regimen
      (seven). The main reason to switching to this dual therapy was toxicity (35
      patients, 75%), mainly renal toxicity attributed to tenofovir (24 cases). During
      104.3 patients-year of follow-up (median 912 days), only two patients (4%) failed
      at 27 and 505 days, due to non-adherence and lost to follow up, respectively.
      Total cholesterol and triglycerides increased significantly during the first six
      months after initiation (TC, from 185 to 269 mg/dL; p=0.01, TG from 118 to 185
      mg/dL; p=0.03, TC/HDL ratio, from 4.09 to 4.66) and decreased after. Median
      estimated glomerular filtration rate (eGFR) improved during follow up (from 86 to
      96.1 mL/min; p=0.13). In patients with renal toxicity as cause of switch there
      was a mild, no significant improvement during the first year (from 63.3 to 68.7
      mL/min), although an improvement in protein-uria levels (protein/creatinine
      ratio, from 171 to 126 mg/g; p=0.04) was observed soon after initiation.
      CONCLUSIONS: Dual therapy with lamivudine plus darunavir boosted with ritonavir
      once daily is safe and effective as simplification strategy in HIV-infected
      patients.

PMID- 25397546
TI  - Switching to boosted protease inhibitor plus a second antiretroviral drug (dual
      therapy) for treatment simplification: a multicenter analysis.
AB  - BACKGROUND: To assess the role of drugs used in dual therapy (DT), as cART
      simplification, over the risk of treatment failure. MATERIALS AND METHODS:
      Patients starting DT regimen composed by a boosted protease inhibitor (PI/r):
      darunavir (DRV/r), lopinavir (LPVr) or atazanavir (ATV/r) plus a second drug:
      raltegravir (RAL), maraviroc (MRV) etravirine (ETR), lamivudine (3TC) or
      tenofovir (TDF), this one generally used in HBV co-infected patients, were
      included. The effect of each drug as well as other clinical and virological
      cofactors over treatment failure was assessed using survival analysis. RESULTS:
      Overall, 480 patients from six reference Italian centres were included: all
      switched to DT with HIV-RNA <500 cp/uL, 376 of them at <50 cp/uL. Patients who
      switched at <50 cp/uL showed a significant lower risk of treatment failure (13.3%
      versus 23.3% at 1 year and 28.0% versus 44.6% at 3 years, p=0.005), thus the
      analysis was focused on this subgroup. Among the patients who switched at <50
      cp/uL, the proportion of drug used in DT was: DRV/r 63.0%, RAL 53.7%, ETR 19.4%,
      ATV/r 18.4%, MRV 17.3%, LPV/r 12.8%, TDF 6.4% and 3TC 5.9%; DRV/r-RAL was the
      most widely used combination: 32.5%. Treatment failure was observed in 78
      patients, of whom 38 virological and 35 for toxicity/intolerance, one patient
      died during follow-up and four patients interrupted for personal decision with
      undetectable HIV-RNA. At Cox Model, adjusted by gender, age, non-Italian origin,
      AIDS diagnosis, time on cART, number of regimens, CD4 nadir, baseline CD4, all
      the drugs had a positive effect on probability of failure (Figure), however the
      effect was significant for DRV/r (HR:0.21, 95% CI 0.07-0.59, p=0.03), ATV/r
      (0.30, 0.09-0.97, p=0.044) and RAL (0.37, 0.15-0.93, p=0.034); higher CD4 count
      at baseline was also associated with lower risk of failure while number of
      previous regimens with a higher risk. Moreover, ATV/r was found significant
      associated with significant higher risk of failure by toxicity (as well as LPV/r)
      but lower risk of virological failure, while both 3TC and RAL with significant
      lower risk of toxicity. CONCLUSIONS: Our analysis suggest that using PI/r-based
      DL is highly effective if switching from HIV-RNA <50 cp/uL; DL should be used
      with caution in patients with low CD4 count and longer history of treatment;
      DRV/r is the best compromise among PI/r, ATV/r is effective but is associate with
      frequent interruption by toxicity; RAL showed high tolerability so that its use
      is related to the lowest risk of failure as second drug.

PMID- 25397547
TI  - Dual therapy with darunavir/r plus etravirine is safe and effective as switching
      therapy in antiretroviral experienced HIV-patients. The BITER Study.
AB  - INTRODUCTION: Switching therapy studies are usually designed as second-line
      antiretroviral treatment (ART) in patients without previous virologic failures.
      Combined ART (cART) with DRV/r and ETR has a good pharmacokinetic profile, high
      genetic barrier and has been proved as rescue therapy. The aim of our study was
      to analyze efficacy and safety of therapy with DRV/r plus ETR in treatment
      experienced HIV-patients with previous therapeutic failures that need to switch
      ART. We present results at first 24 weeks. METHODS: Multicentre retrospective
      observational study. INCLUSION CRITERIA: adult HIV-patients on ART with HIV-VL
      <1000 cop/mL who started their ART with DRV/r (600/100 bid or 800/100 qd)+ETR by
      adverse events, non-adherence, tolerability or prevention of future
      complications. Patients with acute AIDS events, HBV, pregnancy, drug addiction or
      previous selected mutations to DRV or ETR were excluded. RESULTS: Ninety-nine
      patients were included, mean age: 47 years (r: 22-79); 70% men, 40.4% previous
      AIDS event and 39.3% HCV. Ninety-one patients had received >=3 cART regimens and
      45>=5, 75 patients had HIV-VL <50 cop/mL and 24 low-level viremia (LLV): 297.5+/
      261.4 cop/mL, CD4+ 568+/-279 cells/uL. ART before switching: NRTI+PI/r (33%),
      NNRTI (17%), PI/r+NNRTI (23%), PI/r+INI (13%), other (14%). Main reason to
      switching was: toxicity/intolerance 50 patients (renal 32%, gastrointestinal:
      14%, hyperlipidaemia 10%; osteopenia/osteoporosis: 6%); improving adherence 26
      patients; prevention of complications 19 patients. Nine subjects withdrew ART
      during follow-up because: intolerance or new toxicity three; non-adherence two;
      simplification to DRV/r monotherapy two; persistence of previous toxicity one;
      virologic failure one. At week 24, among patients who continued with DRV/r+ETR
      (n=90): 81 (89%) had VL<50 cop/mL, in those with with HIV-VL<50 at baseline
      (67/90), 94% persisted with <50 cop., and in those with LLV (24/90), 61% (n=14)
      achieved a VL<50 cop. We didn't observe any significant difference in lab
      parameters between baseline and week 24. Estimated glomerular filtrate rate
      increased from 83.4+/-24.7 to 88.5+/-56.8 mL/min, p=NS. Regarding reason to
      switching, it improved in 42 cases, no changes: 20 cases; worsened: 4 cases, and
      non-applicable or unknown: 24 cases. CONCLUSIONS: Switching to dual therapy with
      DRV/r+ETR is an effective strategy in selected heavily experienced ART patients,
      even in those with LLV (<1000 cop/mL). This cART is safe and well tolerated, can
      reduce number of pills and improve adherence.

PMID- 25397548
TI  - A clinical and pharmacokinetic study of the combination of etravirine plus
      raltegravir in HIV patients with expanded intolerance or resistance.
AB  - INTRODUCTION: The combination of etravirine (ETR) plus raltegravir (RAL) could be
      an option for HIV patients with resistance, intolerance or important interactions
      with other drugs. However, there are few data on the efficacy, safety and
      pharmacokinetics of this dual therapy, taking into account the effect of HCV co
      infection or the possible induction of ETR in the drug metabolism of RAL.
      MATERIAL AND METHODS: Cohort study of HIV patients initiating ETR plus RAL as
      dual therapy. Plasma trough levels of RAL were measured by LC/MS after at least
      one month on therapy. RESULTS: A total of 25 patients have been included in this
      combination since 2009. Mean age was 46 years, 72% were male, and 20 patients
      (80%) had HCV co-infection (seven patients with fibrosis 3-4). Median nadir CD4+
      count was 109 (60-209), and 21 patients had an HIV RNA level below 50 copies/mL.
      Median time on previous therapy was 473 months (IQR, 395-570), and reasons for
      this dual therapy was toxicity/intolerance in 19, and interactions in nine (two
      chemotherapy, three DAAs, two methadone, two other). After a median follow up of
      722 days (473-1088: 53.3 patients-year), there were no cases of blips or
      virological failure. Six patients (24%) discontinued therapy after more than 1.5
      year on therapy, in four cases due to lost follow up and in two due to
      simplification after finishing the reason for interaction. There were no cases of
      liver toxicity, and only two patients increased slightly transaminases values
      (grade 1 and 2). Total cholesterol and triglycerides levels decrease
      significantly after initiation (TC, from 182 to 165 at one year; p=0.01; TG from
      185 to 143 mg/dL; p=0.01). CT/HDL ratio decreases from 4.35 to 4.28 after six
      months. Geometric mean plasma trough level of RAL was 166 ng/mL (IQR, 40-249) and
      only one patient (6%) was below the in vitro IC50 of the wild type. CONCLUSIONS:
      The combination of ETR plus RAL as dual therapy is effective and safe in patients
      with expanded intolerance or interactions. There are no significant
      pharmacokinetic interactions between both drugs.

PMID- 25397549
TI  - Simplification to Stribild vs continuation of RTV-boosted DRV with FTC and TDF in
      virologically suppressed HIV adults: a STRATEGY-PI subgroup analysis.
AB  - INTRODUCTION: Simplification to Stribild (STB) was statistically superior to
      continuation of a ritonavir-boosted protease inhibitor (PI+RTV) with
      emtricitabine and tenofovir DF (FTC/TDF) at week (W) 48 in virologically
      suppressed HIV adults (1). We report the W48 efficacy and safety of STB versus
      RTV-boosted darunavir (DRV) with FTC/TDF in suppressed subjects. MATERIAL AND
      METHODS: Virologically suppressed subjects on PI+RTV with FTC/TDF regimens for
      >=6 months were randomized (2:1) to switch to STB vs continue their PI regimen.
      Eligibility criteria included no documented resistance to FTC and TDF, no history
      of virologic failure and eGFR >=70 mL/min. The primary endpoint was the
      proportion of subjects in the modified ITT population who maintained HIV-1 RNA
      <50 copies(c)/mL at W48 by FDA snapshot algorithm (12% non-inferiority margin).
      Subgroup analysis by PI use (DRV [173], atazanavir [174], lopinavir [72], Other
      PI [13]) at screening was pre-specified. RESULTS: Four hundred twenty-nine
      subjects were randomized and treated (mITT set). In the DRV subgroup, 113
      switched to STB; 60 continued a RTV-boosted DRV with FTC/TDF. At W48, 95% STB
      versus 92% DRV maintained HIV-1 RNA <50 c/mL. No emergent resistance was detected
      in either group. Median increases from baseline in CD4 count at week 48
      (cells/uL): 28 STB versus 29 DRV (p=0.81). Discontinuations due to adverse events
      were 3% STB versus 2% DRV; one case of isolated decrease in eGFR in the DRV group
      and no cases of proximal renal tubulopathy in either group. There were
      statistically significant decreases in the frequency of diarrhoea reported on the
      HIV Symptom Index at week 4 to week 48 compared to baseline after switching to
      STB. There was a greater but non-progressive decrease from baseline in eGFR in
      the STB vs DRV group; median changes (mL/min) at week 48: -8.5 vs -0.6,
      consistent with the known cobicistat inhibition of renal creatinine secretion.
      Switch to STB was associated with a higher treatment ease (convenience,
      flexibility, demand, lifestyle, understanding) score (range: -15 to 15) at week 4
      (median: 12 vs 9; p=0.006) and week 24 (median: 13 vs 8; p=0.001). CONCLUSIONS:
      In this small group of virologically suppressed subjects, simplification to STB
      versus continuation of a RTV-boosted DRV with FTC/TDF was safe, well-tolerated,
      and associated with a high rate of virologic suppression at week 48. There was
      more treatment ease with STB use.

PMID- 25397551
TI  - Renal safety profile of STB in virologically suppressed subjects from two
      randomized phase 3b switch trials.
AB  - INTRODUCTION: Cobicistat, a component of stribild (STB), is known to inhibit
      renal creatinine secretion. A detailed analysis of the renal safety profile of
      STB in two Phase 3b switch studies of virologically-suppressed individuals on
      stable therapy: STRATEGY(S)-PI (STB vs a RTV-boosted protease inhibitor [PI] with
      emtricitabine and tenofovir DF [FTC/TDF]); and STRATEGY(S)-NNRTI (STB versus a
      non-nucleoside reverse transcriptase inhibitor [NNRTI] with FTC/TDF) is herein
      described. MATERIALS AND METHODS: Baseline eGFR >=70 mL/min was an inclusion
      criterion. The renal safety profile of STB was examined by baseline eGFR through
      week 48 (i.e., changes in eGFR, renal tubular laboratory abnormalities,
      investigator-reported renal adverse events leading to discontinuation and
      unreported subclinical proximal renal tubulopathy [PRT]). Subclinical PRT was
      defined as a confirmed serum-creatinine increase >=0.4 mg/dL and two or three
      markers of renal tubular dysfunction (hypophosphatemia, normoglycemic glycosuria,
      proteinuria) occurring at the same visit at least once and with no alternative
      etiologies. RESULTS: In S-PI, 433 subjects (STB 293; PI 140) and in S-NNRTI, 434
      subjects (STB 291; NNRTI 143) were randomized and treated. Most (>85%) STB
      subjects had a baseline eGFR >=90 mL/min. STB subjects with baseline eGFR <90
      mL/min had smaller declines in eGFR compared to those with baseline eGFR >=90
      mL/min and similar occurrences of renal tubular laboratory abnormalities (Table
      1). Rate of renal adverse events leading to study drug discontinuation were
      similar for the STB group (one PRT in a subject with baseline tubular laboratory
      abnormalities consistent with underlying PRT and one isolated increase in serum
      creatinine) and PI group (one isolated decrease in eGFR); none in the NNRTI
      group. The case of PRT improved after study drug discontinuation. There were no
      cases of unreported subclinical PRT in any group. CONCLUSIONS: In this
      virologically suppressed patient population, the renal safety of STB did not
      differ by baseline eGFR. The renal discontinuation rate was low in the STB group,
      similar to the RTV-boosted PI group, and consistent with published historical
      rates.

PMID- 25397550
TI  - Atazanavir/ritonavir monotherapy as maintenance strategy in HIV-1 treated
      subjects with viral suppression: 96-week analysis results of the MODAT study.
AB  - INTRODUCTION: The 48-week interim analysis of the MODAT study showed that
      confirmed virologic failure (CVF) was more frequent in patients simplifying to
      ATV/r monotherapy compared to maintaining ATV/r-based triple therapy. The DSMB
      recommended stopping study enrollment but continuing follow-up of enrolled
      patients. We present the 96-week efficacy analysis. MATERIAL AND METHODS:
      Multicentre, randomized, open-label, non-inferiority trial (non-inferiority
      margin -10%). Treatment failure (TF) was defined as CVF (two consecutive HIV-RNA
      >50 cp/mL) or discontinuation for any cause. In the monotherapy arm, patients
      with CVF re-introduced their previous NRTIs and remained in the study if HIV-RNA
      <50 copies/mL within 12 weeks of re-intensification. RESULTS: 101 patients
      evaluated (Figure 1): 85% males, 21% HCV-positive, median (IQR) age of 42 (36-48)
      years, baseline CD4+ 576 (447-743) cells/uL. In the 96-week analysis (ITT;
      TF=failure), efficacy was 64% (32/50) in the monotherapy arm and 63% (32/51) in
      the triple-therapy arm (difference +1.3%, 95% CI -17.5-20.1). Fourteen patients
      in monotherapy and two in triple-therapy arm had CVF; median HIV-RNA was 136 (72
      376) copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations
      were observed at CVF. All patients who re-intensified re-suppressed. In
      monotherapy arm, TF was more frequent in HCV-co-infected patients (64% vs 28%;
      p=0.041). In the secondary analysis (ITT; re-intensification=success), 82%
      (41/50) in monotherapy arm and 63% (32/51) in triple-therapy arm were on study at
      week 96 (difference +19.3%, 95% CI 2.2-36.3). SAEs occurred in four (8%) patients
      in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis,
      one traumatic lesion, one nephrolithiasis) and two (4%) in the triple therapy arm
      (one sepsis, one renal failure). Drug-related adverse events (AEs) leading to
      discontinuation were three (6%) in the monotherapy arm (two AEs occurred in
      patients after successful re-intensification) and 12 (23.5%) in the triple
      therapy (p=0.023). CONCLUSIONS: Despite the small sample size, the primary 96
      week analysis showed that simplification to ATV/r monotherapy showed inferior
      efficacy to maintaining ATV/r triple-therapy but appeared to be superior when re
      intensification was considered success.

PMID- 25397552
TI  - Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV
      infected patients: 24-weeks interim analysis from ATLAS-M trial.
AB  - INTRODUCTION: We report interim 24-weeks efficacy data of ATLAS-M trial, a phase
      IV, multicentre, open-label, randomized study designed to show 48-weeks, non
      inferior efficacy (margin of -12%) of treatment simplification to
      atazanavir/ritonavir (ATV/r)+lamivudine (3TC) versus maintaining 3-drugs ATV/r
      based cART. METHODS: Subjects on ATV/r+2 NRTIs, without previous treatment
      failure (TF), with HIV-RNA <50copies/mL for >3 months and CD4>200 cells/mm(3) for
      >6 months were eligible. At baseline, patients were randomized to switch to
      ATV/r+3TC (arm one) or to maintain the original 3-drug regimen (arm two). PRIMARY
      ENDPOINT: proportion of patients free of TF at week 48. TF was defined as
      treatment modification for any reason, including virological failure (VF=two
      consecutive HIV-RNA>50 copies/mL or a single value >1000 copies/mL). Enrollment
      of 266 patients was planned. RESULTS: A total of 266 patients (78% males, median
      age 44 years, median CD4 603 cells/uL, 79% treated with a tenofovir-containing
      backbone) were enrolled. At the time of analysis, 24 weeks data were available
      for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in
      the two arms did not differ for the main characteristics. At 24 weeks, at the
      intention to treat analysis the proportion of patients free of TF was 91.7% (95%
      CI 85.8-97.6) and 85.1% (95% CI 77.6-92.6) in arm one and two, respectively
      (difference +6.6%, 95% CI -2.9/+16.1). VF was observed in two patients randomized
      to arm one (one at baseline, before treatment simplification) and one to arm two
      without resistance mutations. Clinical and laboratory adverse events occurred at
      similar rates in the two arms. At week 24, patients in arm one showed a greater
      increase in CD4 (mean change +90 vs +10 cells/uL, p=0.007). A greater increase in
      total cholesterol (+18 vs -2 mg/dL, p<0.001), HDL (+4 vs +0 mg/dL, p=0.001) and
      LDL (+12 vs +0 mg/dL, p=0.001) was also observed in arm one without differences
      in other lipid parameters. Renal function showed a significant improvement in arm
      one (mean change in eGFR +5 vs -2 mL/min/1.73m(2) in arm two, p=0.001). No
      significant differences in bilirubin levels or other laboratory parameters were
      observed between the two arms. CONCLUSIONS: This interim analysis suggests a 24
      weeks non-inferior efficacy of treatment simplification to ATV/rit+3TC as
      compared to continuation of ATV/rit +2 NRTI in virologically suppressed patients.
      Follow-up until 48-weeks is scheduled to confirm these data.

PMID- 25397553
TI  - Randomized trial of DRV/r or LPV/r QD monotherapy vs maintaining a PI/r-based
      antiretroviral regimen in persons with suppressed HIV replication.
AB  - INTRODUCTION: PI/r monotherapy has been suggested as an attainable maintenance
      strategy in patients achieving stable HIV suppression in plasma. The objective of
      trial was to compare the virological outcome of two different PI/r QD monotherapy
      strategies (LPV/r or DRV/r) with maintaining a triple PI/r-based ARV regimen.
      MATERIAL AND METHODS: Phase III, open-label, non-inferiority (-12% margin),
      randomized trial of HIV adults with HIV-RNA <50 cp/mL for at least 48 weeks while
      on PI/r-based cART, CD4 nadir >100 cell/mm(3), without previous PIs virological
      failure. Eligible patients were randomized to continue PI/r+2NRTIs (Arm A), to
      switch to LPV/r 800/200 mg QD monotherapy (Arm B), or to switch to DRV/r 800/100
      mg QD monotherapy (Arm C). Primary endpoint was proportion of patients with
      plasma HIV-1 RNA <50 cp/mL (TLOVR) at 48w by intent to treat (ITT) analysis
      (missing/re-induction=failure). FDA snapshot and ITT switch-included analysis
      (ITT-SI) were also used. In ITT-SI, patients who had <50 copies/mL at 96w were
      counted as successes even if they had confirmed HIV-RNA elevations and had
      subsequently successfully intensified by NRTI. RESULTS: Due to slow recruitment,
      only 103 patients were included. No differences were observed between the three
      arms with respect to gender, age, HIV transmission, CD4 nadir and at screening.
      At randomization, 61 patients were receiving TDF/FTC (60%), 19 ZDV/3TC (18%), 8
      ABV/3TC (8%), 75 LPV/r (73%), 13 ATV/r (13%), 4 DRV/r (4%). Differences in
      proportion of virological success by groups using Arm A as comparator according
      to FDA TLOVR were reported in Figure 1. Similar results were obtained by Snapshot
      analysis. Of 14 patients with virological failure, 8 patients restarted triple
      therapy with 2NRTI and 7/8 regained a VL <50 cp/mL over time. According to ITT-SI
      analysis, 96 week differences [95% CI] were -5.7 [-29.6; +18.2] in Arm B, and
      +19.6 [-1.6; +40.8] in Arm C. A GRT was performed in 6/14 patients (one not
      amplifiable; four without mutations; one showed E138A). CONCLUSIONS: Compared to
      maintaining a PI/r-based triple ARV regimen, LPV/r QD monotherapy tended to have
      higher rate of virological failure and of discontinuation due to adverse event.
      In contrast, the response rate at week 96 during DRV/r QD mono-therapy was non
      inferior to that of triple PI/r-based ARV therapy. A re-induction with 2NRTI was
      adequate to obtain an undetectable viremia in most of patients with virological
      failure.

PMID- 25397554
TI  - Long term effectiveness of once-daily unboosted atazanavir plus
      abacavir/lamivudine as a switch strategy in subjects with virological
      suppression.
AB  - BACKGROUND: Use of unboosted atazanavir (ATV400) is approved in the US but not in
      Europe (1). Due to pharmacokinetic interactions it should not be used with
      tenofovir but can be used with abacavir/lamivudine (ABC/3TC) (1, 2) (3).
      Effectiveness data of ATV400+ABC/3TC as a switch strategy in clinical routine
      however are scant. METHODS: We evaluated treatment outcomes of ATV400+ABC/3TC in
      pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and
      previous ABC experience or assumed previous HLA B57*01 testing. We performed a
      time to loss of virologic response (TLOVR below 50 c/mL) and a snapshot analysis
      at 48, 96 and 144 weeks. Virological failure (VF) was defined as a confirmed
      plasma HIV-1 RNA >50 c/mL. RESULTS: We included 258 subjects: 176 (68%) male,
      median age 46 (IQR 41, 53) y, 225 (87.2%) white, hepatitis virus co-infection
      36%, median baseline CD4 at switch 540 cells (360, 700), time with VL<= 50 c/mL
      45 (24, 69) months. The median calendar year of switching was 2008 (2006, 2010).
      The 3rd drug in previous regimen was ATV/r in 70 (27.1%), other PI/r in 25
      (9.7%), and other 163 (63.2%); 85 (32.9%) had previously failed with a PI. The
      virological response at 48/96/144 weeks was, respectively, 89.5 [95% CI 85.1,
      92.9]/88 [83.4, 91.7]/86.3% [81.6, 90.4] (TLOVR, composite endpoint failure or
      stop for any reason) and the risk of VF was 8.3/7.6/7.6%. In the snapshot
      analysis HIV-RNA was below 50 c/mL in 72.5/65.9/51.6%, respectively, and >50 c/mL
      in 6.6/5.4/4.3%. Only 0.8/1.9/3.5% discontinued due to adverse events. There was
      a high rate of discontinuations due to other reasons or with VL missing in
      window. In a multivariate adjusted analysis, we observed an association between
      VF and nadir CD4 count (RH 0.60 [0.39, 0.93] per 100 cells higher), time with
      VL<=50 c/mL (RH 0.89 [0.81, 0.98] per 6 months longer) and previous failure with
      a PI (3.04 [1.36, 6.80]). There was no association with gender, age, hepatitis
      virus co-infection, CD4 count at time of switching or third drug used in the
      previous regimen. CONCLUSIONS: A switch to ATV400+ABC/3TC in selected subjects
      with HIV-RNA below 50 c/mL is associated with relatively low rates of VF and
      discontinuation due to adverse events. Use might be considered in those with long
      term suppression and without prior PI failure. Larger cohorts are required to
      further define the appropriate selection criteria.

PMID- 25397555
TI  - Unboosted atazanavir with lamivudine/emtricitabine for patients with long-lasting
      virological suppression.
AB  - INTRODUCTION: Unboosted atazanavir (ATV) including regimens have been
      investigated as a ritonavir-sparing simplification strategy. No data are
      available on removal of one NRTI in subjects effectively treated with unboosted
      atazanavir+2NRTIs. We present the 48-week virological efficacy and safety of
      unboosted atazanavir plus lamivudine (3TC) or emtricitabine (FTC)
      (lamivudine/emtricitabine/Reyataz((c)), LAREY Study). MATERIALS AND METHODS:
      Single arm, prospective, pilot study on HIV-treated patients, HBsAg negative,
      with HIV-RNA<50 cps/mL since at least 2 years, who switched from ATV+2NRTIs to
      ATV 400 mg QD +3TC or FTC. Virological failure was defined as 2 consecutive
      values of HIV-RNA>50 cps/ml; viral blip was defined as a single HIV-RNA value>50
      cps/ml not subsequently confirmed. RESULTS as median (IQR). Changes between
      baseline (BL) and week 48 assessed by the Wilcoxon signed rank test. RESULTS:
      Forty patients enrolled: 75% males, 51 (47-54) years, 14% HCV co-infected,
      infected with HIV since 16 (9-21) years, on antiretroviral therapy since 13 (5
      16) years, with a nadir CD4+ of 254 (157-307) cells/mm(3), virologically
      suppressed since 4.2 (2.2-5.4) years; 53 patients switched from a tenofovir (TDF)
      based regimens; ATV was associated with 3TC in 83% patients. No virological
      failures or discontinuations were observed; three patients had a single viral
      blip in the range 50-250 copies/mL; CD4+ increased from 610 (518-829) cells/mm(3)
      at BL to 697 (579-858) cells/mm(3) at week 48 [48-week change: 39 (-63/+160)
      cells/mm(3) p=0.081]. Three clinical events were observed (one herpes zoster, one
      pneumonia, one syphilis) in absence of renal lithiasis, AIDS-defining or drug
      related events or death. Overall, significant 48-week amelioration of ALP [BL: 83
      (71-107) mg/dL; 48-week change: -15 (-27/-8) mg/dL p<0.0001] and CKD-EPI [BL: 100
      (86-108) ml/min/1.73 m(2); 48-week change: 1.5 (-3/+8) ml/min/1.73 m(2), p=0.042]
      were observed. Patients switching from TDF (Table 1) significantly improved CD4+,
      lymphocytes, hepatic profile, renal profile and ALP; these patients had also a
      modest but significant decrease in haemoglobin. CONCLUSIONS: Switch from an
      unboosted atazanavir-based regimen to ATV+3TC or FTC regimen was effective and
      safe in this small sample, supporting the hypothesis of a potential two-steps de
      intensification (removal of ritonavir and removal of one NRTI) in patients on
      long-lasting virological suppression.

PMID- 25397556
TI  - Simplification to co-formulated rilpivirine/emtricitabine/tenofovir in
      virologically suppressed patients: Data from a multicenter cohort.
AB  - BACKGROUND: To assess efficacy and safety of treatment simplification to co
      formulated Rilpivirine/Emtricitabine/Tenofovir (RPV/FTC/TDF) in virologically
      suppressed patients. MATERIALS AND METHODS: Endpoints of the analysis were: (a)
      treatment discontinuation of RPV/FTC/TDF for any reasons and (b) occurrence of
      virological failure (VF) defined as confirmed HIV-RNA >50 cp/mL). RESULTS:
      Overall, 508 patients from five Italian reference centres were included: male
      gender 71.9%; median age 47 years (IQR 40-52); IVDU as HIV risk 17.7%; HCV-AB
      positive 23.4%; CDC-C stage 17.5%; median CD4 cells/uL at switch 655 (IQR: 487
      843); median number of previous regimens three (IQR 2-7). In a median follow-up
      of 196 days (IQR: 84-287), 31 patients discontinued RPV/FTC/TDF (virological
      failure n=5, hypersensitivity reaction n=2, GI-toxicity n=6, liver toxicity n=1,
      CNS-toxicity n=4, kidney toxicity n=5, patient's decision/lost in follow-up
      n=10). Moreover, VF occurred in eight patients (five discontinued regimen, while
      three remained on RPV/FTC/TDF). At survival analysis, the probabilities of
      treatment discontinuation or VF were 5.5% and 1.2% at 6 months, 13.2% and 2.8% at
      12 months, respectively (Figure 1). At adjusted Cox model, factors associated
      with discontinuation were: <200 CD4 cells/uL at switch (HR 5.3, 95% CI 1.1-25.9,
      p=0.038), number of pre-switch regimens (for each extra regimen: HR 1.05, 95% CI
      1.01-1.10, p=0.024), male gender (HR 0.4, 95% CI 0.2-0.9, p=0.032). Only the
      number of pre-switch regimens was associated with VF (HR 1.13, 95% CI 1.06-1.21,
      p=0.001). Type of pre-switch regimen was not associated with discontinuation or
      failure, but no VF was observed if switching from co-formulated Efavirenz/FTC/TDF
      or from Raltegravir containing regimens. Switching to RPV/FTC/TDF led to
      significant improvement in fasting lipids levels: the decrease in cholesterol,
      LDL and triglycerides was observed switching from any regimen, but was more
      marked from boosted PI. In contrast, a moderate increase in transaminase
      (switching from all regimens except NNRTI-containing) and creatinine (except from
      TDF-containing regimens) were observed. CONCLUSIONS: Our data suggest that
      switching to RPV/FTC/TDF in virologically suppressed patients could be a good
      strategy with low risk of virological failure or treatment discontinuation; the
      switch is also associated with significant improvement in lipid profile.

PMID- 25397557
TI  - Monotherapy with darunavir/ritonavir is effective and safe in clinical practice.
AB  - INTRODUCTION: Monotherapy against HIV has undoubted theoretical advantages and
      has good scientific fundaments. However, it is still controversial and here we
      will analyze the efficacy and safety of MT with darunavir with ritonavir (DRV/r)
      on patients who have received this treatment in our hospitals. MATERIALS AND
      METHODS: Observational retrospective study that includes patients from 10
      Andalusian hospitals that have received DRV/r in MT and that have been followed
      over a minimum of 12 months. We carried out a statistical descriptive analysis
      based on the profile of patients who had been prescribed MT and the efficacy and
      safety that were observed, paying special attention to treatment failure and
      virological evolution. RESULTS: DRV/r was prescribed to 604 patients, of which
      41.1% had a CD4 nadir <200/mmc. 33.1% had chronic hepatitis caused by HCV, had
      received an average of five lines of previous treatment and had a history of
      treatment failure to analogues in 33%, to non-analogues 22 and protease
      inhibitors (PI) in 19.5%. 76.6% proceeded from a previous treatment with PI. The
      simplification was the main criteria for the instauration of MT in the 81.5% and
      the adverse effects in the 18.5%. We managed to maintain MT in 84% of cases, with
      only 4.8% of virological failure (VF) with viral load (VL) >200 c/mL and 3.6%
      additional losses due to VF with VL between 50 and 200 copies/mL. Thirty three
      genotypes were performed after failure without findings of resistance mutations
      to DRV/r or other IPs. Only 23.7% of patients presented some blips during the
      period of exposition to MT. Eighty seven percent of all determinations of VL had
      <50 copies/mL, and only 4.99% had >200 copies/mL. Although up to 14.9% registered
      at some point an AE, only 2.6% abandoned MT because of AE and 1.2% because of
      voluntary decision. Although the average of total and LDL cholesterol increases
      10 mg/dL after 2 years of follow-up, so did HDL cholesterol in 3mg/dL and the
      values of triglycerides (-14 mg/dL) and GPT (-6 UI/mL) decreased. The average
      count of CD4 lymphocytes increased from 642 to 714/mm(3) at 24 weeks.
      CONCLUSIONS: In a very broad series of patients obtained from clinical practice,
      data from clinical trials was confirmed: MT with DRV as a de-escalation strategy
      is very safe, it's associated to a negligible rate of adverse effects and
      maintains a good suppression of HIV replication. VF (with >50 or >200 copies/mL)
      is always under 10% and in any case without consequences.

PMID- 25397558
TI  - ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous
      intolerance to CART. Interim analysis of the PRO-STR study.
AB  - INTRODUCTION: Tolerability and convenience are crucial aspects for the long-term
      success of combined antiretroviral therapy (cART). The aim of this study was to
      investigate the impact in routine clinical practice of switching to the single
      tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART,
      in terms of patients' well-being, assessed by several validated measures.
      METHODS: Prospective, multicenter study. Adult HIV-infected patients with viral
      load under 1.000 copies/mL while receiving a stable ART for at least the last
      three months and switched to RPV/FTC/TDF due to intolerance of previous regimen,
      were included. Analyses were performed by ITT. Presence/magnitude of symptoms
      (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence
      (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through
      48 weeks were performed. RESULTS: Interim analysis of 125 patients with 16 weeks
      of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at
      baseline was 629.5+/-307.29 and 123 (98.4%) had viral load <50 copies/mL; 15%
      were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8%
      from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for
      switching were psychiatric disorders (51.2%), CNS adverse events (40.8%),
      gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this
      analysis (week 16), four patients (3.2%) discontinued treatment: one due to
      adverse events, two virologic failures and one with no data. A total of 104
      patients (83.2%) were virologically suppressed (<50 copies/mL). The average
      degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from
      baseline (21+/-15.55) to week 4 (10.89+/-12.36) & week 16 (10.81+/-12.62),
      p<0.001. In all the patients, quality of life tools showed a significant benefit
      in well-being of the patients (Table 1). Adherence to therapy significantly and
      progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and
      to week 16 (72.0%), p<0.001. CONCLUSIONS: Switching to RPV/FTC/TDF from another
      ARV regimen due to toxicity, significantly improved the quality of life of HIV
      infected patients, both in mental and physical components, and improved adherence
      to therapy while maintaining a good immune and virological response.

PMID- 25397559
TI  - Removing inactive NRTIs in a salvage regimen is safe, maintains virological
      suppression and reduces treatment costs: 96 weeks post VERITAS study.
AB  - INTRODUCTION: In HIV+ patients exhibiting multidrug resistance (MDR), NRTIs often
      have little activity, increased toxicity, drug interactions and add unnecessary
      treatment costs. The 48 week VERITAS study demonstrated that these patients can
      have a safe and effective simplification of salvage regimen by removing inactive
      NRTIs as determined by genotypic data. Virological, immunological, clinical and
      financial outcomes were evaluated at an additional 96 weeks of follow-up.
      MATERIALS AND METHODS: MDR patients with an undetectable viral load (VL) on a
      stable regimen containing at least four ARVs (including one inactive NRTI) were
      enrolled in an open-label, prospective simplification trial, where one inactive
      NRTI was removed at baseline (BL). A second NRTI could be removed at week 24 if
      the regimen contained at least five ARVs at enrolment. RESULTS: 31 male patients
      participated. The mean length of treatment was 14 years, with a median CD4 count
      of 525. The BL regimen consisted of 4 ARVs in 22 patients (71%) and 5 ARVs in 9
      patients (29%). 3TC or FTC was removed in 29 patients (94%), and either AZT or
      TDF was interrupted in 2 others. Four patients had a second NRTI stopped. One
      patient was removed at W26 as an active NRTI was removed for creatinine
      elevation. 30 well-controlled patients continued follow-up after W48. At W144,
      six patients had additional changes in their ARV regimen. Half were due to
      toxicity (jaundice, neuropathy and nephrotoxicity) while the other half were the
      result of treatment simplification. None of the patients exhibited virologic
      failure at the time of treatment change and maintained undetectable VLs
      throughout the entire follow-up. These six patients had a mean gain of 79 CD4
      (p=0.17) compared to baseline. 22 of the 24 patients (92%) with no changes in ARV
      therapy after W48 had undetectable VLs. The other two had confirmed virologic
      failure, one with genotypic resistance. All 24 had elevated CD4 counts (mean +118
      CD4, p<0.0001). No deaths or serious adverse events were observed. One or two ARV
      removals translated to a mean annual saving of $3319 CDN (11%) and $8630 (24%)
      respectively. CONCLUSIONS: Final results indicate that removing one or two
      inactive NRTIs from a regimen in patients taking four or more ARVs with
      controlled VL appears to be safe, maintains virological suppression through 144
      weeks and significantly reduces treatment costs.

PMID- 25397560
TI  - Bone mineral density improvement after 48 weeks of switch to
      maraviroc+darunavir/ritonavir 300/800/100 mg QD, preliminary results of GUSTA
      study.
AB  - INTRODUCTION: Low bone mineral density (BMD) and osteoporosis are prevalent in
      HIV-infected patients and were associated with HIV infection and tenofovir
      containing ART. MATERIALS AND METHODS: The GUSTA study (GUided Simplification
      with Tropism Assay) is a two-arm, prospective, multicenter, 1:1 randomized
      controlled trial designed to demonstrate the non-inferiority of therapeutic
      switch to maraviroc+darunavir/ritonavir (MVC+DRV/r) 300/800/100 mg QD against the
      continuation of previous triple cART in patients with stable virological
      suppression. Enrolment criteria include HIV1-RNA <50 copies/mL for >6 months, R5
      tropism and CD4>200 cells/uL for >3 months. Dual energy X-ray absorptiometry
      scans of proximal femur and lumbar spine were performed at baseline and week 48.
      Bone composition was evaluated using L2-L4 lumbar column and proximal femoral
      BMD, T-score and the Z-score. At the same timepoints, plasma bone metabolism
      biomarkers were measured. Linear regression was used to compare means of
      differences between arms. The association between BMD changes and the baseline
      variables was assessed by linear regression. RESULTS: 27 patients were included,
      13 from study group and 14 from control group, 74.1% were males, 44.4%
      heterosexuals, 81.5% Caucasian, median age was 47 years (IQR 41-53), time from
      HIV diagnosis 13.4 years (9-19), CD4 553/uL (406-739), nadir CD4 201/uL (76-283).
      At baseline, median ART duration was 10.5 years (5.7-15.3), the majority of
      patients (70.4%) was on tenofovir, 63% was on a PI-based regimen and 14,8% on an
      NNRTI-based regimen. Mean proximal femur BMD from baseline increased over 48
      weeks by 2.06% (SD 2.24) in the study arm and decreased by -2.77% (SD 4.63) in
      control arm (p=0.003). The change over 48 weeks in proximal femur T-score was
      significantly different between the study (+0.11, SD 0.22) and control arm (
      1.14, SD 0.27, p=0.016). Also the changes in total alkalin phosphatase (-20 U/L
      vs -1.5, p=0.003) was significant between the two groups. After adjusting for
      time from HIV diagnosis and years of ART, study group was the only factor
      associated to higher mean percentage change from baseline femoral BMD (MVC+DRV/r
      +4.83, p=0.044). CONCLUSIONS: The study demonstrated a significant improvement in
      femoral BMD and T-score after treatment simplification with MVC+DRV/r.

PMID- 25397561
TI  - Switching to lamivudine plus darunavir/r dual therapy in a cohort of treatment
      experienced HIV-positive patients: the experience of an Italian centre.
AB  - INTRODUCTION: According to recent evidence about boosted protease inhibitors
      (PIs/r)-simplified regimens, the combination of 3TC and DRV/r 800/100 mg could
      represent a feasible option for optimizing antiretroviral therapy (ART) in
      treatment-experienced HIV+ patients. PATIENTS AND METHODS: We retrospectively
      evaluated patients switching to 3TC+DRV/r, with at least six months of viral
      suppression, no resistance mutation to DRV or 3TC and not HBV-coinfected:
      incidence of ART discontinuation and of virological failure (VF: 2 consecutive
      HIV-RNA determinations>49 cps/mL or a single one>=1000 cps/mL) and the
      probability of remaining discontinuation-free during one-year follow-up (FU), as
      well as changes in laboratory parameters at 1, 3, 6 and 12 months were estimated.
      RESULTS: We included 94 patients: 74 males, mostly MSM (39.4%), with 49 years
      old, 9 years of HIV disease, 8 years of ART (median values). Median nadir CD4
      count and zenith viral load (log10) were 194 cells/uL and 4.90, respectively. Ten
      patients were HCV-coinfected and 38 had at least a previous VF. Seventy-four
      patients were on an NRTIs-based triple regimen (mainly TDF/FTC or 3TC/ABC)
      whereas 14 on another PI-based dual therapy (mainly LPV/r). Incidence of
      treatment discontinuation was 12.4 per 100 patients-year follow-up (PYFU), but
      only 2 patients experienced a VF (3.5 per 100 PYFU). Mean time free from
      discontinuation was 5 years (95% CI 4-6), with a cumulative one-year estimated
      probability of staying on 3TC+DRV/r of 85.9%. At three months, a trend of
      increased CD4 cells count (+42 cells/uL, p 0.059) was observed, but not confirmed
      at later time point; an increase of total cholesterol (TC, +17mg/dL, p 0.008) and
      LDL (+19 mg/dL, p 0.002), and a decreased level of AST and ALT (-2 UI/L, p 0.045;
      -5 UI/L, p 0.009, respectively) were also detected. Total bilirubin was reduced (
      0.71 mg/dL, p 0.038). At 6 and 12 months, alteration of lipid profile was
      similar, with also an increased TC/HDL ratio (+0.48, p=0.030, at six months) and
      HDL/LDL ratio (-0.04, p=0.035, at 12 months). A significant decrease in ALT
      levels (-6 UI/L, 0.013) and a diminishing trend for AST and total bilirubin, as
      well as a significant increase in renal function (GFR +4mL/min, p 0.048) were
      observed at 12 months. CONCLUSIONS: These observations on 3TC+DRV/r-based dual
      therapy simplification in virologically suppressed patients show a good profile
      of efficacy and safety. An extended FU time is needed in order to establish the
      real impact of this promising therapeutic choice.

PMID- 25397562
TI  - Safety and therapeutic efficacy of the switch to maraviroc+darunavir/ritonavir in
      HIV/HCV coinfected patients: initial results from GUSTA study.
AB  - INTRODUCTION: HIV/HCV coinfection is a risk factor for hepatic injury in patients
      receiving HAART and previous studies support a favourable effect of
      antiretroviral regimens including maraviroc (MVC) on the course of coinfection
      compared with other antiretroviral drugs. There are few observations about MVC
      use in simplified treatment of coinfected patients. OBJECTIVE: To evaluate the
      efficacy and the safety of simplification to darunavir (DRV)/ritonavir
      (r)/maraviroc (MVC) in virologically HIV-suppressed patients and to explore the
      effect of simplified treatment on coinfected patients. MATERIAL AND METHODS:
      GUSTA study is a randomized two arms trial that compares the switch to DRV/r/MVC
      with standard HAART with three drugs. The study enrols patients with HIV-1
      RNA<50cp/mL>6 months, R5 tropism, CD4>200 cells/mm. Survival analysis was used to
      analyze factors associated to time-to a single viral load (VL) over 50cp/mL and
      FIB-4>1.45. RESULTS: We included 62 patients with at least the 24 week follow-up
      for FIB-4 analysis: males 75.8%, heterosexuals 48.4%, HCV+12.9% median age 48.3
      years (IQR41.1;53.5), time from HIV diagnosis 11.0 years (IQR7.3;16.7), CD4 cells
      659/mm (IQR478;882), nadir CD4 203/mm (IQR115;286), FPR 46 (IQR30;70), baseline
      (BL) FIB-4 1.11 (IQR0.75;1.35). At BL no differences were observed in the two
      arms, except for platelets (-34.96 109/L, in the study arm, p=0.028) and CD4 at
      nadir (-70cell/uL, p0.051). After 24 weeks a significant reduction in total
      bilirubin (TB) (-0.55 mg/dL, p=0.025) and alkaline phosphatase(AP) (-12.96 UI/L,
      p=0.002) was observed in the study group. A statistically significant difference
      in mean change of TB (0.61 mg/dL, p=0.016) and AP (13.23 UI/L, p=0.04) at 24 week
      between control and study group was observed. No grade 3/4 transaminase elevation
      was observed for any patient even if HIV/HCV coinfected and receiving MVC. A
      single HCV negative patient in the control arm had grade 3 bilirubin increase.
      Including all patients with at least one follow-up HCV status was not associated
      with an increased risk of detectable VL (n=114, 4072 person-week-follow-up
      [IQR12;51.6]), nor with FIB-4>1.45 (n=98, 3513 person-week-follow-up
      [IQR11.4;50.9]). CONCLUSIONS: The initial results from GUSTA study show that ART
      regimen including MVC did not increase the incidence of adverse events or severe
      laboratory liver abnormalities in HIV-1-infected patients with or without HCV
      coinfection. Coinfected patients did not show an increased risk of failure on
      simplification treatment with MVC/DRV/r.

PMID- 25397563
TI  - Nuke-sparing regimens as a main simplification strategy and high level of
      toxicity resolution after antiretroviral switch: the SWITCHART Study.
AB  - BACKGROUND: The advent of combined antiretroviral therapy (ART) in the past
      decade has led to HIV suppression in most cases. Virological failure was the main
      reason for ART switch a few years ago; however, toxicity and treatment
      simplification have now gained importance due to the availability of more
      effective and convenient drugs. This study assessed the reasons for ART switch in
      daily practice. MATERIAL AND METHODS: Observational retrospective study that
      included patients whose ART was switched between January 2011 and July 2012.
      Patients with any other switch during the follow-up period (until September 2013)
      were excluded. RESULTS: A total of 246 patients were included. Main reasons for
      ART switch were simplification (33%) and toxicity (31%), followed by clinical
      trial inclusion (13%), virological failure (6%), drug interaction (4%), patient
      decision (3%), lack of adherence (2%), pregnancy (1%) and other (8%). Eighty
      patients switched to a simpler regimen (median age 48 [40-53], mean CD4 count
      608+/-265 cells/cl, 89% <50 copies/ml, mean number of previous regimens 6+/-5,
      mean time on previous ART 3+/-2 years). In this case, previous ART mostly
      included 2NRTI+1PI/r (54%) (Figure 1). The simplification strategy mainly
      contained nuke-sparing regimens (60%) based on PI (DRV/r 48%): monotherapy 46%,
      dual therapy 13% (PI/r+maraviroc 9%, PI/r+NNRTI 4%) and triple therapy 1%
      (PI/r+maraviroc+raltegravir). The second preferred simplification option was
      2NRTI+1NNRTI (24%). Seventy-seven patients switched due to toxicities (median age
      47 [43-53], mean CD4 count 606+/-350 cells/MUl, <50 copies/ml 82%, mean number of
      previous regimens 4+/-3, mean time on previous ART 3+/-3 years). Renal (25%) and
      CNS (18%) toxicities were the main reasons for ART switch, followed by diarrhoea
      (16%), liver enzyme elevation (ALT 10%; AST 9%; bilirubin 7%), lipid elevation
      (cholesterol 5%; triglycerides 8%), nausea (7%) and other (=5%) (Figure 2). All
      patients with renal toxicity were under TDF and in most cases this drug was
      removed from the new regimen (with 3TC/ABC or nuke-sparing). Among patients with
      CNS toxicity, 79% were taking EFV; the main new treatment was a second-generation
      NNRTI (ETR)+2NRTI. Toxicities were completely resolved in 66% of patients,
      partially resolved in 22% and not resolved in only 12%; the median time from ART
      switch to toxicity resolution was 4 (2-8) months. CONCLUSIONS: The main reasons
      for ART switch in daily practice are simplification and toxicities, renal and CNS
      toxicities being the most prevalent. The preferred simplification strategies are
      nuke-sparing regimens, mainly DRV/r-based monotherapy and dual therapy. ART
      switch leads to a complete resolution of toxicities in most cases in the short
      term.

PMID- 25397564
TI  - The importance of viral blips and duration of therapy initiated in primary
      infection in maintaining viral control after stopping cART.
AB  - INTRODUCTION: After achieving undetectable HIV-RNA on cART, on cessation, HIV-RNA
      rebounds to pre-treatment values for the majority due to the presence of an
      inaccessible viral reservoir. There is some evidence that cART during primary HIV
      infection (PHI) limits the reservoir size, optimizing the chance of maintaining
      viral control off cART. Data are required to predict possible viral controllers
      for treatment interruption following cART. This analysis aims to investigate the
      effect of cART duration and the rate of viral blips while on cART initiated in
      PHI, and other factors on maintaining viral control for those stopping cART.
      MATERIAL AND METHODS: Using CASCADE data on HIV seroconverters, we characterized
      virologic blip (viral suppression on cART followed by a single HIV-RNA above a
      blip threshold and a subsequent measure below the threshold without cART change)
      rates for those starting cART within six months of seroconversion (SC). Using Cox
      models, we examined the effect of the following factors on time to virologic
      rebound (HIV-RNA>1000) after cART stop: cART duration, severity/rate of blips on
      cART, time from SC to cART start, cART class, SC year, SC age, CD4 at cART
      start/stop, sex and HIV risk group. RESULTS: The 660 individuals initiating cART
      in PHI were mostly male (91%), seroconverting between 1995 and 2012, with a
      median (IQR) age of 34 (29, 41) years mostly infected through sex between men
      (73%). Median cART duration was 14.8 (7.0, 31.7) months initiated at a median 1.9
      (0.5, 3.9) months post SC. 13 (11, 16), 9 (7, 11), 6 (5, 9) and 7 (6, 10)% of
      individuals experienced blips >50, 100, 200 and 400 copies/mL, respectively. Of
      those who experienced blips, most (77-90%, depending on blip threshold)
      experienced just one. Among 250 individuals with undetectable HIV-RNA at cART
      stop, median time to rebound was 1.6 (0.30, 5.8) months. Time on cART was the
      only factor independently associated with control after stopping, HR for
      rebound=0.91 (0.86, 0.98) per extra six months spent on cART, HR for ever
      blipping >400 copies/mL while on cART=0.88 (0.40, 1.93). CONCLUSIONS: Blips occur
      in about 10% of individuals who initiate cART in PHI, most of who experience only
      one blip, but was not predictive of subsequent virologic rebound. Increasing time
      spent on cART initiated in PHI could increase time of virological suppression
      after cART stop.

PMID- 25397565
TI  - DRV concentrations and viral load in CSF in patients on DRV/r 600/100 or
      800/100mg once daily plus two NRTI.
AB  - INTRODUCTION: Darunavir/r (DRV/r) is currently used at a dose of 800/100 mg once
      daily (OD) in a high proportion of patients. Pharmacokinetic data suggest that
      600/100 OD may be effective, reducing toxicity and cost. However, drug
      concentrations in reservoirs such as cerebrospinal fluid (CSF) might not be
      adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV
      and HIV-1 viral load (VL) in CSF patients receiving DRV 600/100 mg OD. METHODS:
      DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800) vs
      600/100 mg (DRV600) OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed
      patients (eudraCT 2011-006272-39). Here we present the results of a CSF sub
      study. A lumbar puncture (LP) was performed in participating patients after at
      least six months of inclusion in the study, 20-28 hours after a dose of DRV/r. VL
      (PCR, LOD 40 copies/mL) was determined in CSF and in plasma. DRV concentrations
      were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS) and
      in plasma using high-performance liquid chromatography (HPLC). RESULTS: Sixteen
      patients were included (eight in each arm). All DRV600 patients and four out of
      eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were
      males, median (range) age was 48 (17-71) years, CD4 cell count 532 cells/mL (190
      1,394). Median total time on DRV/r was 30 (11-57) months, and since the beginning
      of the study 8 (6-12) months in DRV800 and 10 (7-12) months in DRV600 patients.
      LP was performed a median of 26 (24-28) hours after the last DRV/r+TVD or KVX
      dose. In DRV600 patients the median DRV plasma levels were 1,674 (326-3,742)
      ng/mL, CSF levels 17.08 (5.79-30.19) ng/mL and DRV CSF:plasma ratio 0.0084
      (0.0028-0.0388), while in the DRV800 arm, median DRV plasma levels were 1,707
      (958-3,910) ng/mL, CSF levels 13.23 (3.47-32.98) ng/mL and DRV CSF:plasma ratio
      0.0104 (0.0018-0.0262). All patients had VL<40 copies/mL in plasma and 14
      patients VL<40 copies/mL in CSF. Two patients (1 in each arm, and taking TDF/FTC)
      had detectable VL in CSF (280 and 159 c/mL). These patients had the lowest CSF
      DRV concentrations (5.47 and 3.47 ng/mL), with plasma DRV concentrations of 802
      and 958 ng/mL respectively. CONCLUSIONS: CSF DRV concentrations and CSF VL were
      similar between patients receiving DRV/r 800/100 mg or 600/100 mg OD. Low CSF DRV
      concentrations might be associated with viral escape in CNS. This may be taken
      into account in patients receiving OD DRV/r. Larger studies should confirm these
      findings.

PMID- 25397566
TI  - Efficacy of a reduced dose of DARUNAVIR/RTV in a cohort of antiretroviral-naive
      and experienced HIV-infected patients: a medium-term follow-up.
AB  - BACKGROUND: The currently approved dose of darunavir/ritonavir is 800/100 mg once
      daily for PI-naive patients, and 600/100 mg twice daily for PI-pretreated
      patients. However, in DRV-sensitive patients at baseline in the POWER 1/2 trials,
      similar rates of HIV RNA suppression (1 log reduction) were achieved with doses
      ranging from 400/100 mg once daily to 600/100 mg twice daily. In previously
      virologically suppressed patients, a reduced dose of DRV (600/100 QD) is non
      inferior to the standard dose (800 mg QD)1 and DRV concentrations in plasma and
      CSF are similar in patients receiving the above different doses (1, 2). METHODS:
      Twelve treatment-naive patients were started on darunavir/ritonavir 600/100mg
      once daily, with TDF/FTC (8) or ABC/3TC (4). Seven patients were switched to
      darunavir/ritonavir 600/100 mg once daily, with TDF/FTC (2), ABC/3TC (2), NVP
      (1), AZT/3TC (1). One was on monotherapy with DRV. Seven treatment-experienced
      patients were switched to darunavir/ritonavir 600/100 mg once daily, with TDF/FTC
      (5), ABC/3TC (1), RAL (1). RESULTS: Of the 12 naive patients (mean baseline HIV
      RNA 134,024 log10 copies/mL, range 4,256-397,932), 11 had HIV RNA <20 c/mL after
      a mean 27.4 months of follow-up (range 12-33). Mean PK level was 2,920 ng/mL
      (1,268-4,562). One patient had virological failure after 14 months (HIV RNA
      39,300 copies/mL); no mutations were detected and after introduction of DRV/r 600
      mg b.i.d., he returned aviremic. All switched patients maintained HIV RNA
      suppression (<20 c/mL) for a mean of 32.8 months (range 21-54). PK level was
      available for one patient only (Ctrough 3,442 ng/mL). Of the treatment
      experienced patients (mean baseline HIV RNA 24,167 log10 copies/mL, range 112
      111,426), five maintained HIV RNA suppression for a mean of 46.2 months (range 31
      67). One patient interrupted HAART for three months and then restarted it, the
      latest HIV RNA level being 628 copies/mL after five weeks of therapy. One patient
      failed after 42 months (HIV RNA 3,930 copies/mL); after intensification (DRV/r
      600 twice daily), he returned aviremic. PK levels were available for three
      patients (mean 2,502 ng/mL; range 844-4,518). CONCLUSIONS: In this pilot study of
      26 patients, use of DRV/r at 600/100 mg OD dose led to sustained HIV RNA
      suppression in 23 patients with acceptable PK exposures to DRV. Large non
      inferiority trials are warranted to establish its efficacy.

PMID- 25397567
TI  - The impact of nevirapine- versus protease inhibitor-based regimens on virological
      markers of HIV-1 persistence during seemingly suppressive ART.
AB  - INTRODUCTION: The source and significance of residual plasma HIV-1 RNA detection
      during suppressive ART remain controversial. It has been proposed that nevirapine
      (NVP)-based regimens achieve a greater HIV-1 RNA suppression than regimens
      containing a protease inhibitor (PI). The aim of this study was to compare the
      effect of receiving NVP- vs PI-based ART on the virological markers of HIV
      persistence in peripheral blood. MATERIAL AND METHODS: The study population
      comprised 161 HIV-1 infected patients receiving either NVP-based (n=81) or PI
      based (n=80) ART and showing a HIV-1 RNA load stably suppressed <40 copies/mL for
      median of 5.2 years (IQR 2.2-8.0). Residual viraemia was detected by real-time
      PCR with 50% and 95% detection thresholds of 1 and 3 HIV-1 RNA copies/mL,
      respectively. Cell-associated (CA) unspliced HIV-1 RNA, total HIV-1 DNA and 2 LTR
      circles were quantified in peripheral blood mononuclear cells (PBMCs) using
      droplet digital PCR. Groups were compared by standard non-parametric tests;
      factors associated with HIV-1 detection were analyzed by univariate regression
      analysis and generalized linear models (SPSS(r) V22 and Rstudio). RESULTS: Plasma
      HIV-1 RNA was detected in 37/81 (45.7%) and 47/80 (58.8%) subjects on NVP- and PI
      based ART, with median (IQR) levels of 5 (3-6) and 5 (3-8) copies/mL,
      respectively. HIV-1 RNA detection was associated with shorter duration of
      suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir
      (p=0.015). HIV-1 DNA levels were median 282 (120-484) and 213 (87-494) copies/106
      PBMCs in the two groups respectively, and were lowest (<100 copies/106 PBMCs) in
      subjects with lower plasma HIV-1 RNA (p=0.049), CA unspliced HIV-1 RNA
      (p=0.0001), 2 LTR circles (p=0.005) and pre-ART HIV-1 RNA load (p=0.0001).
      CONCLUSIONS: In this comprehensive characterization of patients on long-term
      suppressive ART, we did not observe evidence for a greater suppressive activity
      of NVP-based over PI-based therapy on plasma and intracellular markers of virus
      persistence. Overall excellent correlation was observed between the markers,
      allowing the identification of a subset of treated patients with low HIV-1
      expression as an important cohort for future HIV cure studies.

PMID- 25397568
TI  - Switching from ritonavir to cobicistat in HIV patients with renal impairment who
      are virologically suppressed on a protease inhibitor.
AB  - INTRODUCTION: Cobicistat (COBI) is a pharmacoenhancer and one of the components
      of ECF/TDF (elvitegravir/cobicistat/emtricitabine/tenofovir DF), which is
      approved in treatment-naive HIV patients with creatinine clearance (CrCl) >=70
      mL/min. Study 118 assessed the renal safety of COBI-containing regimens in HIV
      patients with mild to moderate renal impairment. MATERIAL AND METHODS: Phase 3,
      open label study in HIV-1-infected patients with CrCl 50-89 mL/min who are
      virologically suppressed on a stable regimen containing ritonavir (RTV)-boosted
      atazanavir (ATV) or darunavir (DRV). Patients switched RTV to COBI, while keeping
      the rest of their regimen unchanged. We present the 96-week (Wk) data. RESULTS:
      Seventy-three patients were enrolled. Mean age was 54 years; male 82%; white 77%;
      hypertension 38%; diabetes 18%; baseline proteinuria (>=trace) 51%; median CrCl
      71 mL/min (range: 42-98). At Wk 96, 89% maintained virologic suppression (95% CI
      77.4-95.8%). No emergent resistance developed. Reductions in CrCl (median [IQR])
      were observed as early as Wk 2, after which they were nonprogressive through Wk
      96 (Wk 48: -3.8 [-9-0.8]; Wk 96: -5.0 [-13.0-0.1]). Changes in CrCl by baseline
      CrCl (<70 vs >=70) at Wk 96 were: -3.1 [-5.1-0.5] vs -7.6 [-15.2 to -3.6],
      respectively. Cystatin C-based eGFR remained stable through Wk 96 (median [IQR]: 
      2.8 [-7.4-8.9 mL/min/1.73 m(2)). Actual GFR assessment using CLiohexol (n=14) was
      unaffected over 24 Wks (median at baseline: 82.5, median changes from baseline at
      Wks 2, 4, and 24: 1.6, 7.0, -4.1 mL/min, respectively). Three renal
      discontinuations occurred (two worsening CrCl and one proteinuria/hematuria);
      none had proximal renal tubulopathy [PRT]. No patient had laboratory evidence of
      PRT (>1 confirmed renal laboratory abnormalities [increase in serum Cr>=0.4
      mg/dL, >=2-grade increase in proteinuria,>=1-grade increase in normoglycemic
      glycosuria or hypophosphatemia]). CONCLUSIONS: In HIV-infected patients with CrCl
      50-89 mL/min, on ATV- or DRV-based regimen switching to COBI from RTV,
      demonstrated that COBI was well tolerated with no cases of PRT through 96 Wks.
      The renal safety profile of COBI in patients with mild to moderate renal
      impairment was consistent with the long-term data in patients without renal
      impairment (CrCl>=70 mL/min) from the phase 3 studies of COBI-containing
      regimens.

PMID- 25397570
TI  - Hypovitaminosis D in HIV-infected patients in Lisbon: a link with antiretroviral
      treatment.
AB  - INTRODUCTION: Recent data indicates that low vitamin D (25(OH)D) levels can lead
      to a worst prognosis in HIV-infected individuals, even in those on successful
      antiretroviral therapy (ART) [1]. Portugal is the European country that has the
      largest average sun exposure time but prevalence of hypovitaminosis D is mostly
      unknown. Our aim was to determine the prevalence of hypovitaminosis D in HIV
      patients in Lisbon and the possible association with ART. METHODS: From 2012 to
      January 2014, plasma samples from 518 HIV-infected patients were collected to
      25(OH)D levels determination. Data on demographic features (age, ethnicity,
      country of origin) and clinical/laboratory parameters were collected from
      clinical files (HIV subtype, CD4+ cell count, CD4+ nadir, viral load (VL),
      HBV/HCV co-infection and ART). 25(OH)D status was defined as: deficiency <20
      ng/mL, insufficiency 20-30 ng/mL, optimal >30 ng/mL. RESULTS: Median age was 46
      years old (+/-11); 62.0% (321/518) were male; 81.3% (421/518) were Caucasian and
      78.6% (407/518) were Portuguese. Most patients (96.1%; 498/518), were HIV-1
      infected, 22.9% (114/498) and 4.0% (20/498) of them were HCV and/or HBV co
      infected, respectively. Mean CD4+ cell count was 648 cells/uL (+/-333) and nadir
      was 219 cells/uL (+/-179). On treated patients VL was <40 HIV RNA/mL in 86.7%
      (417/481). The median levels of 25(OH)D was 20.0 ng/mL (range 4.1-99.7) and we
      found differences between values observed during Winter (median 16.7 ng/mL) and
      Summer (median 24.9 ng/mL) (p<0.0001). Low 25(OH)D levels were not correlated to
      ethnicity (p=0.066). 25(OH)D level was <30 ng/mL in 80.1% (415/518) of the
      patients, from which 30.9% (160/518) and 49.2% (255/518) had insufficiency and
      deficiency levels, respectively. Most (92.9%; 481/518) were on ART: regimens
      containing PI (47.5%), NNRTI (40.3%; 41.3% on NVP and 58.7% on EFV), II (1.2%),
      PI+NNRTI (3.9%). Comparing the 25(OH)D level along the different ART regimens (PI
      vs NVP; PI vs EFV; PI vs no ART) there were differences between PI and EFV
      (p=0.044). CONCLUSIONS: In this study, 80.1% of the HIV-infected patients had
      hypovitaminosis D and ART regimens with EFV were more often associated with low
      25(OH)D levels. Understanding the impact of the different antiretroviral drugs on
      25(OH)D status could help to decide in clinical practice whether 25(OH)D
      supplementation or drug switch are the best options for each patient.

PMID- 25397569
TI  - Treatment discontinuation in HIV-1-infected individuals starting their first-line
      HAART after 2008: data from the ICONA Foundation Study Cohort.
AB  - INTRODUCTION: The aim of this study was to analyze the likelihood and the
      predictors of discontinuation of first-line regimen in the late HAART era.
      METHODOLOGY: An observational multi-center analysis of HIV-positive patients
      enrolled in ICONA. Patients eligible were those starting a first-line HAART after
      1 January 2008. Discontinuation was defined as stop and/or switch of at least one
      drug of the regimen. All causes of discontinuation, as reported by the treating
      physician, were evaluated and cumulative risk of stopping was investigated
      according to age, gender, co-morbidity, years since starting HAART, immuno
      virological status, third drug and backbone of the first regimen. Kaplan Meier
      (KM) analysis and Cox proportional hazards model were used for the outcome
      discontinuation of >=1 drug regardless of the reason. For the KM estimates a
      competing risk approach was used to estimate the contribution of each of the
      reasons over time to the cumulative risk of stopping over time. RESULTS: Data of
      1759 patients who started first HAART and had at least one month of clinical
      follow-up were analyzed. The overall discontinuation risk was 33% over a median
      follow-up of 12 months. The likelihood of discontinuation by KM was 27% by one
      year (95% CI 25-29) and 41% by two years (95% CI 38-44). Main reason for stopping
      at least one drug in regimen was simplification (10%), followed by intolerance
      (7%), toxicity (5%), failure (2%) and other causes (8%). Estimates of the
      cumulative risk of discontinuation of >=1 drug over time and according to reason
      are shown in Figure 1. In a multivariable Cox model independent predictors of
      discontinuation regardless of the reason were: longer time from HIV diagnosis to
      date of starting HAART (hazard ratio [HR] 0.96; 95% CI 0.93-1.00; p=0.039),
      regimens containing ZDV/3TC (HR 2.86; 95% CI 1.42-5.76; p=0.003 vs TDF/FTC) and
      an NNRTI-based regimen (HR 2.47; 95% CI 0.91-6.72; p=0.07 vs regimens not NNRTI
      based). CONCLUSIONS: In a previously reported analysis of the ICONA data (1), the
      overall risk of discontinuation of first-line HAART was 36% with 21% due to
      intolerance/toxicity. In this updated analysis, the main reason for stopping is
      simplification (accounting for 32% of stops), reflecting the recent changes in
      recommendations aimed to minimize drug toxicity, enhancing adherence and quality
      of life.

PMID- 25397571
TI  - Effect of hyperbilirubinaemia on neurocognitive, renal, bone and cardiovascular
      markers in HIV infection treated with boosted protease inhibitors.
AB  - INTRODUCTION: Use of some protease inhibitors (PI) is associated with
      unconjugated hyperbilirubinaemia (HBR), due to inhibition of UGT1A1. As observed
      in Gilbert's syndrome, HBR may have antioxidant and anti-inflammatory effects.
      Inflammation may be relevant to neurocognitive (NC) impairment, cardiovascular,
      renal and bone co-morbidities in HIV infection. This study aimed to analyse
      correlations between antiretroviral associated HBR and NC impairment as well as
      renal, bone and cardiovascular parameters. MATERIAL AND METHODS: This cross
      sectional study included 101 HIV-1-infected individuals stable (>6 months) on
      antiretroviral regimens including tenofovir/emtricitabine or abacavir/lamivudine
      plus a ritonavir-boosted PI. Patients with >grade 2 HBR were compared to patients
      with normal bilirubin on NC data collected using CogState. An overall composite
      score was calculated for each subject. Two-tail P-values were calculated using
      the Mann-Whitney U test. We measured the following parameters in all
      participants: Bone - Calcaneal Stiffness Index (CSI), blood bone markers,
      calculated FRAX score; CV - vascular endothelial function markers (iCAM, vCAM),
      lipid fractions and sub fractions (Total, HDL and LDL cholesterol, triglycerides,
      ApoB), Carotid Intimal Thickness (CIT), Pulse Wave Velocity (PWV), glucose and
      insulin for calculation of HOMA-IR, IL-6, d-dimer, uric acid, and hsCRP; Renal -
      urea and electrolytes (U&E), urinary protein/creatinine ratio (uPCR), urinary
      retinal binding protein (RBP)/creatinine ratio. RESULTS: Forty-three participants
      had normal bilirubin (NBR) levels and 35 had high bilirubin (HBR; >2.5 times
      upper limit); the remaining 23 patients had intermediate bilirubin levels or
      violated the protocol. The mean age of participants was 48 years; 93% were male
      and 84% Caucasian. Mostly no significant differences were seen in any of the
      markers when comparing the NBR and HBR groups. Two component tests of the
      CogState were seen to be different - visual learning and memory (OCL) and working
      memory (ONB) (Table 1). CONCLUSIONS: The numbers seen here were not felt to be
      large enough to draw clear conclusions around clinical significance. In the
      context of overall cognitive screening, the individual test differences were also
      not felt to be clinically significant. Clearly there are some early signs here of
      differences that may be worth investigating further in a larger, prospective
      study.

PMID- 25397572
TI  - Low level HIV viremia is more frequent under protease-inhibitor containing
      firstline therapy than under NNRTI-regimens.
AB  - INTRODUCTION: An association of persistent low level viremia (LLV) below 500
      copies/mL and a higher risk of therapy failure is still point of controversial
      discussion. Furthermore, it seems that LLV occurs more frequently in patients
      with protease-inhibitor regimens than in NNRTI- / or integrase-inhibitor
      containing therapies. The focus of this work was to assess the prevalence of LLV
      (50-200 copies/mL) and weak viremia (201-500 copies/mL) in firstline-treated
      patients according to their therapy regimen. METHODS: A total of 832 and 944
      patients from 23 German centres were under firstline therapy in 2012 and 2013,
      respectively. All patients received their therapy for more than 24 weeks. VL data
      was related to clinical data retrospectively including ART-composition,
      subdivided into NNRTIs (Efavirenz, Nevirapine), PIs (Atazanavir, Darunavir,
      Lopinavir) and INIs (Raltegravir). Low viremic patients were classified into two
      arms of 50-200 copies/mL (group A) and 201-500 copies/mL (group B). RESULTS:
      Success of therapy was defined as <50 copies/mL and was observed in 90.0% and
      91.1% (2012/2013), respectively. An additional 2.0% and 2.3% had LLV. The amount
      of viremic patients with VLs <500 copies/mL differed significantly between NNRTI
      based firstline regimens 1.7% and 2.5% and PI-based regimens 4.8% and 5.7%
      (2012/2013), respectively. LLV was clearly less often observed in EFV-based-
      (1.6% and 1.1% [group A] / 0.4% and 0.4% [group B]) or NVP-based firstline
      therapies (1.0% and 3.6% [group A] + 0% and 0% [group B]) than in ATV-based-
      (7.5% and 3.8% [group A] + 1.5% and 2.5% [group B]), DRV-based- (2.9% and 3.0%
      [group A] + 2.2% and 0% [group B]) or LPV-based firstline therapies (1.6% and
      3.3% [group A] + 0.8% and 2.5% [group B]) and also in parts for RAL-based
      regimens (0% and 3.7% [group A] + 0% and 1.9% [group B]). CONCLUSIONS: LLV is
      more often observed under PI-based firstline than under NNRTI-regimens. Only one
      NNRTI-patient of group B remained on therapy. A possible explanation for this
      discrepancy might be the fact that physicians seem to tolerate LLV more often in
      PI-regimens than in NNRTI-regimens due to a higher genetic barrier against
      resistance and it remains a point of discussion if constant LLV does affect
      immune recovery and risk of therapy failure.

PMID- 25397573
TI  - Clinical and laboratorial impact of antiretroviral therapy in a cohort of
      Portuguese patients chronically infected with HIV-2.
AB  - INTRODUCTION: HIV-2 infection is endemic in West Africa and some European
      countries, namely Portugal. HIV-2 antiretroviral (ARV) treatment presents some
      restrains related to intrinsic resistance to non-nucleoside reverse transcriptase
      inhibitors (NNRTI) and fusion inhibitors, and poorer response to protease
      inhibitors (PI). MATERIAL AND METHODS: Retrospective observational study of a
      cohort of 135 infected HIV-2 patients, diagnosed between 1989 and 2008.
      OBJECTIVES: Evaluation of epidemiologic, clinical, immunologic and virologic
      progression, comparing to groups of patients (naive vs ARV experienced);
      characterization of therapeutic, immunologic and virologic response. SPSS version
      20.0 was used for statistical analysis. RESULTS: The study included 135 patients:
      41% (n=55) naive and 59% (n=80) with ARV experience. The comparison between
      groups (naive vs ARV) revealed: male prevalence 76% vs 50%; mean age 54.5 years
      vs 54.8 (p=0.90); main geographic origin Guine Bissau (47% vs 44%) and Portugal
      (22% vs 33%); and transmission mainly acquired by heterosexual contact (87% vs
      80%). Mean time since diagnosis was 14 vs 13 years (p=0.31); 2% vs 50% presented
      AIDS criteria at diagnosis (p<0.001) and 93% vs 38% registered TCD4>350
      cell/mm(3) at diagnosis (p<0.001). Immunological evolution showed no significant
      decline in naive population (Delta=-67 cell/mm(3) - p=0.18) and a significant
      recovery in ARV experienced (Delta=+207 cell/mm(3) - p<0.001). Global mortality
      rate found was 18% (6% vs 13% - p=0.122). Eighty patients initiated ARV: 84%
      presented a time interval of ARV exposure between 0-5 years (42%) and 5-10 years
      (42%). Fifty percent experienced <=2 ARV regimens and the remaining >2 regimes.
      Considering the first ARV therapy: 56% initiated PI, 30% NTRI and 5% integrase
      inhibitor (II)-based regimens. Currently, 54 patients maintain regular follow-up
      and ARV therapy: 60% NTRI+PI; 37% NRTI+PI+II and 3% NRTI+II. TDF/FTC is the
      backbone in 56%. Most frequent PIs are LPV/r (54%), DRV/r (19%) and ATV/r (12%).
      Mean time of exposure to NRTI=3 years, PI=7 years and II=2 years. Immunologic
      recovery was sustained for each of the ARV class considered (NRTI Delta=+144
      cell/mm(3); PI=Delta+92 cell/mm(3); II=Delta=+116 cell/mm(3)). CONCLUSIONS: This
      is a cohort accompanied for a long period and the majority of patients present
      extensive ARV experience. The ARV-experienced patients registered a favourable
      response to treatment, with sustained immune recovery (Delta=+207 cell/mm(3)) and
      virologic control in 74%. Immunologic behaviour evidenced a sustained gain for
      each of the ARV class considered.

PMID- 25397574
TI  - Factors involved in treatment durability and immunological recovery in a cohort
      of HIV-positive patients receiving atazanavir-based regimens.
AB  - INTRODUCTION: Since antiretroviral therapy must be taken lifelong, persistence
      and safety have become the goals to achieve. Protease inhibitors, in particular
      atazanavir (ATV) with or without ritonavir (r), represent a highly prescribed
      class in real life long-term treatment. METHODS: We conducted a retrospective
      cohort study in HIV-1-positive patients who were followed at the Infectious
      Diseases Unit, DIBIC Luigi Sacco, University of Milan. Data regarding viral load,
      CD4 lymphocytes and the mean blood chemistry parameters were collected at
      baseline, first, third, sixth months from the beginning of therapy and then every
      six months. Factors related to persistence of therapy with ATV and time-dependent
      probability to reach a CD4 cells count >500 cells/uL were evaluated with Kaplan
      Meier curve and Cox model. RESULTS: A total of 1030 patients were evaluated: 183
      received therapy with ATV/r as naive, 653 switched to ATV/r as a second or
      following line and 194 switched to unboosted ATV from previous ATV-free regimens.
      A total of 138 patients shifted to unboosted ATV from a previous ATV/r regimen
      (17 from naive ATV/r and 121 from experienced ATV/r). The median duration of
      therapy was 38 months (95% CI 29-73) in ATV/r naive patients, 36 months (95% CI
      23-53) in unboosted ATV group and 35 months (95% CI 31-43) in patients switched
      to ATV/r. We observed no significant difference in the persistence of the three
      regimens (p=0.149). Female (HR=1.317; 95% CI 1.073-1.616 p=0.008) and patients
      with CD4<200 cells/uL at baseline (HR=1.433 95% CI 1.086-1.892 p=0.011) were at
      increased risk of regimen interruption, whereas starting therapy with a backbone
      containing abacavir (HR=0.725; 95% CI 0.533-0.987 p=0.041) resulted protective.
      In multivariate analysis no significant difference between the three regimens was
      observed regarding reaching a count of CD4 cells >500 cells/uL. Factors
      associated to a poor CD4 gain were each extra Log of viral load at baseline
      (HR=0.915; 95% CI 0.852-0.982 p=0.014) and CD4<200 cells/uL at ATV start
      (HR=0.197; 95%CI 0.138-0.281 p<0.0001); conversely, females (HR=1.262; 95%CI
      1.032-1.543 p=0.023) had a higher probability of CD4 recovery. CONCLUSIONS:
      Antiretroviral regimens containing atazanavir with or without ritonavir were
      durable and well tolerated, an elevated viral load and CD4 <200 cells/uL at
      baseline resulted related to regimen discontinuation and reduced CD4 recovery.

PMID- 25397575
TI  - Recreational drugs and HIV in Europe: current use of recreational drugs and
      principal HIV guidelines related recommendations.
AB  - INTRODUCTION: Recreational drug consumption has been associated with both higher
      rates of risk activities related to HIV transmission and also worse adherence and
      management of HIV patients under HAART treatment. Moreover, relevant interactions
      may be present in patients under HAART treatment. Our aim is to present the
      European trends of drug consumption per country and age groups and assess the way
      drug consumption is addressed in general HIV guidelines. MATERIALS AND METHODS:
      Last 12-month prevalence drug use was obtained from the European Monitoring
      Centre for Drugs and Drug Addiction for the four most consumed drugs (cannabis,
      cocaine, amphetamines, ecstasys). Consumption rates were collected and analyzed
      by country and age. Principal HIV guidelines were assessed to identify the degree
      of incorporation of drug use issues at three levels: transmission risk, adherence
      to the HAART and management of interactions. GUIDELINES: (a) WHO; (b) EACS; (c)
      BHIVA; (d) US DHHS; (e) IAS-USA; (f) GESIDA; (g) French CPG; (h) Italian CPG.
      RESULTS: Data on drugs of abuse consumption was obtained from 29 European
      countries, with results showing relevant drug utilization in Europe. Cannabis was
      the most frequent drug across all countries, with 10 countries over 5% of
      prevalence over the last year. Other drugs prevalence accounted for about 0.5-1%,
      reaching up to: 2.1% for cocaine in Spain, 1.4% for ecstasy in the Netherlands
      and 1.1% for amphetamines in Estonia. 15-24 and 25-34 years old subgroups had the
      highest prevalence, although notable use of cannabis and cocaine was also found
      in the 35-44 and 45-54 subgroups. From the eight guidelines assessed, six
      considered recreational drugs at any point. Recommendations for specific drugs
      were given in 50% of the guidelines. From those guidelines addressing drug
      consumption: three assessed risk habits which related to transmission risk, six
      appraised issues on adherence to HAART and five comprised data on interactions
      between recreational drugs and HAART. Additionally, five guidelines mentioned
      drugs in the context of other issues, such as sexual dysfunction or HIV
      associated neurocognitive impairment. CONCLUSIONS: Use of recreational drugs is
      frequent in Europe, not only in the younger population but also in other
      unexpected older subgroups. The scarce information found in the guidelines has a
      potential implication for patients and clinicians; therefore, there is a need to
      include specific recommendations about the clinical management of people living
      with HIV who use recreational drugs.

PMID- 25397576
TI  - Cardiac Health Risk Stratification System (CHRiSS): a Bayesian-based decision
      support system for left ventricular assist device (LVAD) therapy.
AB  - This study investigated the use of Bayesian Networks (BNs) for left ventricular
      assist device (LVAD) therapy; a treatment for end-stage heart failure that has
      been steadily growing in popularity over the past decade. Despite this growth,
      the number of LVAD implants performed annually remains a small fraction of the
      estimated population of patients who might benefit from this treatment. We
      believe that this demonstrates a need for an accurate stratification tool that
      can help identify LVAD candidates at the most appropriate point in the course of
      their disease. We derived BNs to predict mortality at five endpoints utilizing
      the Interagency Registry for Mechanically Assisted Circulatory Support
      (INTERMACS) database: containing over 12,000 total enrolled patients from 153
      hospital sites, collected since 2006 to the present day, and consisting of
      approximately 230 pre-implant clinical variables. Synthetic minority oversampling
      technique (SMOTE) was employed to address the uneven proportion of patients with
      negative outcomes and to improve the performance of the models. The resulting
      accuracy and area under the ROC curve (%) for predicted mortality were 30 day:
      94.9 and 92.5; 90 day: 84.2 and 73.9; 6 month: 78.2 and 70.6; 1 year: 73.1 and
      70.6; and 2 years: 71.4 and 70.8. To foster the translation of these models to
      clinical practice, they have been incorporated into a web-based application, the
      Cardiac Health Risk Stratification System (CHRiSS). As clinical experience with
      LVAD therapy continues to grow, and additional data is collected, we aim to
      continually update these BN models to improve their accuracy and maintain their
      relevance. Ongoing work also aims to extend the BN models to predict the risk of
      adverse events post-LVAD implant as additional factors for consideration in
      decision making. 

PMID- 25397577
TI  - Suppression of enhanced physiological tremor via stochastic noise: initial
      observations.
AB  - Enhanced physiological tremor is a disabling condition that arises because of
      unstable interactions between central tremor generators and the biomechanics of
      the spinal stretch reflex. Previous work has shown that peripheral input may push
      the tremor-related spinal and cortical systems closer to anti-phase firing,
      potentially leading to a reduction in tremor through phase cancellation. The aim
      of the present study was to investigate whether peripherally applied mechanical
      stochastic noise can attenuate enhanced physiological tremor and improve motor
      performance. Eight subjects with enhanced physiological tremor performed a
      visuomotor task requiring the right index finger to compensate a static force
      generated by a manipulandum to which Gaussian noise (3-35 Hz) was applied. The
      finger position was displayed on-line on a monitor as a small white dot which the
      subjects had to maintain in the center of a larger green circle. Electromyogram
      (EMG) from the active hand muscles and finger position were recorded. Performance
      was measured by the mean absolute deviation of the white dot from the zero
      position. Tremor was identified by the acceleration in the frequency range 7-12
      Hz. Two different conditions were compared: with and without superimposed noise
      at optimal amplitude (determined at the beginning of the experiment). The
      application of optimum noise reduced tremor (accelerometric amplitude and EMG
      activity) and improved the motor performance (reduced mean absolute deviation
      from zero). These data provide the first evidence of a significant reduction of
      enhanced physiological tremor in the human sensorimotor system due to application
      of external stochastic noise. 

PMID- 25397578
TI  - PR3-ANCA: a promising biomarker in primary sclerosing cholangitis (PSC).
AB  - BACKGROUND AND AIMS: The only recognized biomarker for primary sclerosing
      cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA),
      which, in addition to having low sensitivity and specificity, is an indirect
      immunofluorescence (IIF) test lacking the advantages of high throughput and
      objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA)
      might add diagnostic value in inflammatory bowel disease (IBD), specifically in
      ulcerative colitis (UC). As PSC is associated with IBD, the objective of this
      study was to evaluate the frequency and clinical significance of PR3-ANCA in a
      large cohort of patients. METHODS: A total of 244 PSC and 254 control [autoimmune
      hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection
      (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their
      clinical correlations were retrospectively analyzed for PR3-ANCA determined by
      ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed
      for aANCA by IIF. RESULTS: When measured by CIA, PR3-ANCA was detected in 38.5%
      (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By
      ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7%
      (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the
      presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's
      disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in
      PSC measured by CIA correlated with higher liver enzymes. CONCLUSION: PR3-ANCA is
      detected in a significant proportion of PSC patients compared to other liver
      diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme
      levels in PSC, and is not solely related to underlying IBD.

PMID- 25397579
TI  - Kinetics and mechanism of photopromoted oxidative dissolution of antimony
      trioxide.
AB  - Light (sunlight, ultraviolet, simulated sunlight) irradiation was used to
      initiate the dissolution of antimony trioxide (Sb2O3). Dissolution rate of Sb2O3
      was accelerated and dissolved trivalent antimony (Sb(III)) was oxidized in the
      irradiation of light. The photopromoted oxidative dissolution mechanism of Sb2O3
      was studied through experiments investigating the effects of pH, free radicals
      scavengers, dissolved oxygen removal and Sb2O3 dosage on the release rate of
      antimony from Sb2O3 under simulated sunlight irradiation. The key oxidative
      components were hydroxyl free radicals, photogenerated holes and superoxide free
      radicals; their contribution ratios were roughly estimated. In addition, a
      conceptual model of the photocatalytic oxidation dissolution of Sb2O3 was
      proposed. The overall pH-dependent dissolution rate of Sb2O3 and the oxidation of
      Sb(III) under light irradiation were expressed by r = 0.08 .[OH(-)](0.63) and rox
      = 0.10 .[OH(-)](0.79). The present study on the mechanism of the photo-oxidation
      dissolution of Sb2O3 could help clarify the geochemical cycle and fate of Sb in
      the environment.

PMID- 25397581
TI  - One-step process for the synthesis and deposition of anatase, two-dimensional,
      disk-shaped TiO2 for dye-sensitized solar cells.
AB  - We report a one-step process for the synthesis and deposition of anatase, two
      dimensional (2D), disk-shaped TiO2 (DS-TiO2) using titanium isopropoxide (TTIP),
      ethyl cellulose (EC), and solvents. The planar structure of EC plays a pivotal
      role as the sacrificing template to generate the 2D disk-shaped structure with a
      thickness of 1.5-3.5 MUm, while a disk-like structure was well developed in the
      tetrahydrofuran (THF)/toluene mixed solvent. The quasi-solid-state dye-sensitized
      solar cells (qssDSSCs), fabricated with a nanogel electrolyte and a DS-TiO2 layer
      on a nanocrystalline (NC)-TiO2 photoanode, showed an energy conversion efficiency
      of 5.0% without any TiCl4 post-treatment, which is higher than that fabricated
      without DS-TiO2 (4.2%). When utilizing a poly((1-(4-ethenylphenyl)methyl)-3-butyl
      imidazolium iodide) (PEBII) as the solid electrolyte, a high efficiency of 6.6%
      was achieved due to the combination of high mobility PEBII and a bifunctional DS
      TiO2 layer with a 2D structure and anatase phase. The bifunctionality of the DS
      TiO2 layer allows greater light scattering back into the device and provides
      additional surface area for improved dye adsorption, resulting in short circuit
      current density (Jsc).

PMID- 25397580
TI  - Comparative genomic analysis shows that avian pathogenic Escherichia coli isolate
      IMT5155 (O2:K1:H5; ST complex 95, ST140) shares close relationship with ST95 APEC
      O1:K1 and human ExPEC O18:K1 strains.
AB  - Avian pathogenic E. coli and human extraintestinal pathogenic E. coli serotypes
      O1, O2 and O18 strains isolated from different hosts are generally located in
      phylogroup B2 and ST complex 95, and they share similar genetic characteristics
      and pathogenicity, with no or minimal host specificity. They are popular objects
      for the study of ExPEC genetic characteristics and pathogenesis in recent years.
      Here, we investigated the evolution and genetic blueprint of APEC pathotype by
      performing phylogenetic and comparative genome analysis of avian pathogenic E.
      coli strain IMT5155 (O2:K1:H5; ST complex 95, ST140) with other E. coli
      pathotypes. Phylogeny analyses indicated that IMT5155 has closest evolutionary
      relationship with APEC O1, IHE3034, and UTI89. Comparative genomic analysis
      showed that IMT5155 and APEC O1 shared significant genetic overlap/similarities
      with human ExPEC dominant O18:K1 strains (IHE3034 and UTI89). Furthermore, the
      unique PAI I5155 (GI-12) was identified and found to be conserved in APEC O2
      serotype isolates. GI-7 and GI-16 encoding two typical T6SSs in IMT5155 might be
      useful markers for the identification of ExPEC dominant serotypes (O1, O2, and
      O18) strains. IMT5155 contained a ColV plasmid p1ColV5155, which defined the APEC
      pathotype. The distribution analysis of 10 sequenced ExPEC pan-genome virulence
      factors among 47 sequenced E. coli strains provided meaningful information for B2
      APEC/ExPEC-specific virulence factors, including several adhesins, invasins,
      toxins, iron acquisition systems, and so on. The pathogenicity tests of IMT5155
      and other APEC O1:K1 and O2:K1 serotypes strains (isolated in China) through four
      animal models showed that they were highly virulent for avian colisepticemia and
      able to cause septicemia and meningitis in neonatal rats, suggesting zoonotic
      potential of these APEC O1:K1 and O2:K1 isolates. 

PMID- 25397583
TI  - A cascade of acid-promoted C-O bond cleavage and redox reactions: from oxa
      bridged benzazepines to benzazepinones.
AB  - A sequence of C-O bond cleavage and redox reactions in oxa-bridged azepines was
      realized under acid promoted conditions. This protocol provides an atom
      economical and straightforward approach to access benzo[b]azepin-5(2H)-ones in
      high yields. The formal synthesis of tolvaptan was achieved by exploiting this
      new transformation. 

PMID- 25397582
TI  - Hyper-theory-of-mind in children with Psychotic Experiences.
AB  - BACKGROUND: Alterations in Theory-of-Mind (ToM) are associated with psychotic
      disorder. In addition, studies in children have documented that alterations in
      ToM are associated with Psychotic Experiences (PE). Our aim was to examine
      associations between an exaggerated type of ToM (HyperToM) and PE in children.
      Children with this type of alteration in ToM infer mental states when none are
      obviously suggested, and predict behaviour on the basis of these erroneous
      beliefs. Individuals with HyperToM do not appear to have a conceptual deficit
      (i.e. lack of representational abilities), but rather they apply their theory of
      the minds of others in an incorrect or biased way. METHOD: Hypotheses were tested
      in two studies with two independent samples: (i) a general population sample of
      1630 Danish children aged 11-12 years, (ii) a population-based sample of 259
      Dutch children aged 12-13 years, pertaining to a case-control sampling frame of
      children with auditory verbal hallucinations. Multinomial regression analyses
      were carried out to investigate the associations between PE and ToM and HyperToM
      respectively. Analyses were adjusted for gender and proxy measures of general
      intelligence. RESULTS: Low ToM score was significantly associated with PE in
      sample I (OR = 1.6 95%CI 1.1-2.3 chi2(4) = 12.42 p = 0.010), but not in sample II
      (OR = 0.9 95%CI 0.5-1.8 chi2(3) = 7.13 p = 0.816). HyperToM was significantly
      associated with PE both in sample I (OR = 1.8, 95%CI 1.2-2.7 chi2(3) = 10.11 p =
      0.006) and II (OR = 4.6, 95%CI 1.3-16.2 chi2(2) = 7.56 p = 0.018). HyperToM was
      associated particularly with paranoid delusions in both sample I (OR = 2.0,
      95%CI: 1.1-3.7% chi2(4) = 9.93 p = 0.021) and II (OR = 6.2 95%CI: 1.7-23.6%
      chi2(4) = 9.90 p = 0.044). CONCLUSION: Specific alterations in ToM may be
      associated with specific types of psychotic experiences. HyperToM may index risk
      for developing psychosis and paranoid delusions in particular.

PMID- 25397584
TI  - Assessing Polarizability Models for the Simulation of Low-Frequency Raman Spectra
      of Benzene.
AB  - Optical Kerr effect (OKE) spectroscopy is a widely used technique for probing the
      low-frequency, Raman-active dynamics of liquids. Although molecular simulations
      are an attractive tool for assigning liquid degrees of freedom to OKE spectra,
      the accurate modeling of the OKE and the motions that contribute to it relies on
      the use of a realistic and computationally tractable molecular polarizability
      model. Here we explore how the OKE spectrum of liquid benzene, and the underlying
      dynamics that determines its shape, are affected by the polarizability model
      employed. We test a molecular polarizability model that uses a point anisotropic
      molecular polarizability and three other models that distribute the
      polarizability over the molecule. The simplest and most computationally efficient
      distributed polarizability model tested is found to be sufficient for the
      accurate simulation of the many-body polarizability dynamics of this liquid. We
      further find that the atomic-to-molecular polarizability transformation
      approximation [Hu et al. J. Phys. Chem. B 2008, 112, 7837-7849], used in
      conjunction with this distributed polarizability model, yields OKE spectra whose
      shapes differ negligibly from those calculated without this approximation,
      providing a substantial increase in computational efficiency. 

PMID- 25397585
TI  - Kinetics of evaporation and gel formation in thin films of ceramic precursors.
AB  - Precursors derived from the hydrolysis of organic or inorganic salts have been
      widely used to produce ceramic coatings for a broad variety of applications. When
      applying the liquid precursors to the substrates, it is extremely challenging to
      control the film uniformity and homogeneity. The rate of solvent evaporation at
      different locations is different, causing the viscosity variation and flows in
      the film. There is very limited knowledge about the viscosity change in
      evaporating ceramic precursors. Therefore, it is crucial to understand the effect
      of evaporation on viscosity variation in thin films and droplets. We use magnetic
      rotational spectroscopy to study the time dependence of viscosity in mullite
      precursors. A correlation between the viscosity change and evaporation kinetics
      is revealed. This correlation was used to relate the change of viscosity to the
      concentration of mullite. A master curve relating viscosity to the mullite
      concentration was constructed and used to propose a possible scenario of the
      viscosity increase during solvent evaporation. 

PMID- 25397586
TI  - Second primary cancers in the Vaud and Neuchatel Cancer Registries.
AB  - An increasing proportion of new cancers is registered in patients who have
      received a previous cancer diagnosis. As data are inconsistent across studies, we
      provided information for populations long covered by valid cancer registration.
      Data were derived from the Swiss cancer Registries of Vaud and Neuchatel (885,000
      inhabitants). Patients diagnosed with a new malignancy (except skin basal and
      squamous cell carcinomas) during the period 2005-2010 were included. Over the
      period 2005-2010, 24,859 patients were registered with incident cancer. Of these,
      3127 (13%) had multiple primary cancers and 578 (2.3%) were synchronous. Breast,
      prostate, colorectum, skin, melanomas, and squamous cell carcinomas of the head
      and neck (SHN) and bladder/ureter were the most common sites of first neoplasms,
      whereas breast, lung, colorectum, prostate, melanoma, and SHN were the most
      common sites of second neoplasms. The most common pairing was breast with breast
      (31% synchronous), followed by the bladder/ureter with the prostate (72%
      synchronous), prostate with the colorectum, SHN with SHN, and SHN with lung. Five
      year crude survival of patients with synchronous cancers (34%) was not
      significantly lower than that of patients with single neoplasms (39%). This
      population-based study indicates that about one in eight incident neoplasms in
      these mature registries are second neoplasms and almost 1/40 patients are
      diagnosed with synchronous primary cancers. These are related to shared genetic
      and environmental factors as well as diagnostic and therapeutic procedures. As
      cancer diagnosis and survival is likely to improve, the proportion of patients
      with multiple primary cancers will further increase in the future.

PMID- 25397587
TI  - Safety, Feasibility, and Efficacy of Capecitabine Maintenance in Patients With
      Advanced Gastric Cancer: A Retrospective Study.
AB  - Gastric cancer is still one of the cancers with highest mortality. Most patients
      present with advanced-stage disease. Palliative chemotherapy is usually the only
      treatment option for patients with advanced gastric cancer (AGC). Maintenance
      chemotherapy is an evolving concept in medical oncology. Maintenance chemotherapy
      can be administered with the same drug(s) in the initial regimen or with an
      alternative agent. In this article, we report our experience with capecitabine as
      a maintenance agent for patients with AGC. No treatment-related death was
      observed due to use of capecitabine. Median progression-free survival was 10.4
      months, and median overall survival was 19.7 months. Activity and toxicity
      profile of capecitabine seems favorable as a maintenance agent in AGC. We believe
      that capecitabine deserves further trials as a maintenance agent for patients
      with AGC.

PMID- 25397588
TI  - Aortoduodenal fistula in a patient on intravitreal bevacizumab injections: a case
      report.
AB  - An 88-year-old woman on long-term intravitreal bevacizumab presented with acute
      gastrointestinal hemorrhage. She was stabilized and underwent nonrevealing upper
      endoscopy. She continued to require intermittent blood transfusions, and
      resulting computed tomography of the abdomen revealed an aortoduodenal fistula.
      The patient was undergoing treatment for her macular degeneration with
      intravitreal bevacizumab, an angiogenesis inhibitor frequently used to treat
      solid organ malignancies. Systemic administration has been associated with
      serious adverse events, including gastrointestinal hemorrhage, perforation, and
      fistula formation. Intravitreal bevacizumab has been used off-label to treat
      macular degeneration, but data on the safety of this therapy are limited. Given
      her lack of other risk factors, the authors postulate a potential association
      between intravitreal bevacizumab and aortoduodenal fistula formation in this
      patient. 

PMID- 25397589
TI  - Interactions between colloidal particles in the presence of an ultrahighly
      charged amphiphilic polyelectrolyte.
AB  - A novel amphiphilic polyelectrolyte denoted as PAGC8 and a traditional
      amphiphilic polyelectrolyte denoted as PASC8 were prepared. PAGC8 consisted of
      gemini-type surfactant segment based on 1,3-bis (N,N-dimethyl-N-octylammonium)-2
      propyl acrylate dibromide, while PASC8 incorporated acryloyloxyethyl-N,N-dimethyl
      N-dodecylammonium bromide as single chain surfactant units within its repeat unit
      structure. Turbidity, stability, and zeta potential measurements were performed
      in the presence of PAGC8 and PASC8, respectively, to evaluate their effectiveness
      in inducing solid/liquid separations. It was found that the maximum transmittance
      was observed before the zeta potential values reached the isoelectric point,
      implying that not only charge neutralization but also charge-patch mechanism
      contributed to the separation process. Colloid probe atomic force microscopy
      technique was introduced to directly determine the interactions between surfaces
      in the presence of ultrahighly charged amphiphilic polyelectrolyte. On the basis
      of the AFM results, we have successfully interpreted the influence of the charge
      density of the polyelectrolytes on the phase stability. Electrostatic interaction
      played the dominant role in the flocculation processes, although both
      electrostatic interaction and hydrophobic effect provided contributions to the
      colloidal dispersions. The attractions upon surfaces approach in the case of
      PAGC8 were significantly larger than that of PASC8 due to the higher charge
      density. The strong peeling events upon retraction in the presence of PAGC8
      implied that the hydrophobic effect was stronger than that of PASC8, which
      displayed the loose pulling events. A strong attraction was identified at shorter
      separation distances for both systems. However, these interactions cannot be
      successfully described by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of
      colloid stability due to the participation of charge-patch and strong hydrophobic
      effect. To account for the additional interactions, we proposed an extended DLVO
      empirical model to explain the non-DLVO forces in the systems. A reasonable
      physical model was also proposed to further describe the interactions between
      surfaces in the two amphiphilic polyelectrolyte systems. 

PMID- 25397590
TI  - Ground and excited electronic state analysis of PrF2+ and PmF2+.
AB  - The ground state and excited state manifolds are computed for PrF(2+) and PmF(2+)
      at the CASSCF (n,8) level of theory where the active space spans the Ln 4f
      orbitals as well as the F 2pz orbital. Dynamical correlation is included using
      second-order multireference quasidegenerate perturbation theory (MCQDPT2). The
      spin-orbit multiplets for each of the excited states are resolved, and spin-orbit
      coupling constants are computed using the Breit-Pauli spin-orbit operator.
      Equilibrium geometries for each of the ground and excited states are computed,
      and the nature of the Ln-F bond is examined. Potential energy curves for the
      lowest four triplet states and lowest two quintet states are computed for
      PrF(2+), which split into 14 levels upon application of the spin-orbit
      Hamiltonian. Likewise, the lowest six quintet states are computed for PmF(2+) as
      well as the lowest triplet state and the lowest two septet states. These nine
      states split into 43 terms upon application of the spin-orbit Hamiltonian. 

PMID- 25397591
TI  - Kinetic effects of sulfur oxidation on catalytic nitrile hydration: nitrile
      hydratase insights from bioinspired ruthenium(II) complexes.
AB  - Kinetic investigations inspired by the metalloenzyme nitrile hydratase were
      performed on a series of ruthenium(II) complexes to determine the effect of
      sulfur oxidation on catalytic nitrile hydration. The rate of benzonitrile
      hydration was quantified as a function of catalyst, nitrile, and water
      concentrations. Precatalysts L(n)RuPPh3 (n = 1-3; L(1) = 4,7-bis(2'-methyl-2'
      mercapto-propyl)-1-thia-4,7-diazacyclononane; L(2) = 4-(2'-methyl-2'
      sulfinatopropyl)-7-(2'-methyl-2'-mercapto-propyl)-1-thia-4,7-diazacyclononane;
      L(3) = 4-(2'-methyl-2'-sulfinatopropyl)-7-(2'-methyl-2'-sulfenato-propyl)-1-thia
      4,7-diazacyclononane) were activated by substitution of triphenylphosphine with
      substrate in hot dimethylformamide solution. Rate measurements are consistent
      with a dynamic equilibrium between inactive aqua (L(n)Ru-OH2) and active nitrile
      (L(n)Ru-NCR) derivatives with K = 21 +/- 1, 9 +/- 0.9, and 23 +/- 3 for L(1) to
      L(3), respectively. Subsequent hydration of the L(n)Ru-NCR intermediate yields
      the amide product with measured hydration rate constants (k's) of 0.37 +/- 0.01,
      0.82 +/- 0.07, and 1.59 +/- 0.12 M(-1) h(-1) for L(1) to L(3), respectively.
      Temperature dependent studies reveal that sulfur oxidation lowers the enthalpic
      barrier by 27 kJ/mol, but increases the entropic barrier by 65 J/(mol K). Density
      functional theory (DFT) calculations (B3LYP/LanL2DZ (Ru); 6-31G(d) (all other
      atoms)) support a nitrile bound catalytic cycle with lowering of the reaction
      barrier as a consequence of sulfur oxidation through enhanced nitrile binding and
      attack of the water nucleophile through a highly organized transition state. 

PMID- 25397592
TI  - Septo-optic dysplasia associated with congenital persistent fetal vasculature,
      retinal detachment, and gastroschisis.
AB  - PURPOSE: The purpose of this study was to report the association of septo-optic
      dysplasia, persistent fetal vasculature, retinal detachment, and gastroschisis in
      a preterm neonate. METHODS: This is a case report. RESULTS: A female preterm
      neonate was found to have septo-optic dysplasia, with optic nerve hypoplasia,
      tripartite splitting of the vessels at the optic nerve, an ectopic pituitary
      gland, and absence of the septum pellucidum associated with persistent fetal
      vasculature, a retinal detachment, and gastroschisis. CONCLUSION: Septo-optic
      dysplasia may also be associated with other ophthalmic findings and other
      developmental malformations as the authors report in this case. Follow-up should
      consist of a multidisciplinary approach with radiologic and endocrinology
      consultation.

PMID- 25397593
TI  - Upconversion: when two wrongs make a right.

PMID- 25397594
TI  - Impact of masking effect on subclinical carotid atherosclerosis in normotensives
      and untreated masked hypertensive and hypertensive patients.
AB  - OBJECTIVES: The masking effect (ME) is present in masked hypertensive patients;
      however, both normotensive and hypertensive individuals may show a similar
      phenomenon. Previous studies have shown that ME has been associated with left
      ventricular hypertrophy and microalbuminuria in treated hypertensive patients.
      The aim of our study was to evaluate the association between the magnitude of
      systolic ME and the extent of common carotid artery intima-media thickness (CCA
      IMT) development in normotensive individuals and untreated masked hypertensive
      and hypertensive patients. PARTICIPANTS AND METHODS: A total of 1154 individuals
      underwent 24 h ambulatory blood pressure (BP) monitoring and carotid artery
      ultrasonographic measurements. The final study population included 360 patients
      with systolic ME (daytime systolic BP higher than office systolic BP). The
      participants were divided into three groups according to office and daytime BP
      values: normotensives, masked hypertensives, and hypertensives. RESULTS: Masked
      hypertensives presented significantly higher systolic ME (-14.6 mmHg) than their
      normotensive (-8.2 mmHg) and hypertensive (-9.5 mmHg) counterparts. However,
      systolic ME was associated significantly with CCA-IMT only in the group of masked
      hypertensives (r=-0.399, P<0.001). The multivariate linear regression analyses
      showed significant and independent associations of CCA-IMT with the following
      factors: age (B=0.028, 95% confidence interval: 0.001-0.055; P=0.044) and
      systolic ME (B=-0.034, 95% confidence interval: -0.066 to -0.003; P=0.034). A 10
      mmHg decrease in systolic ME correlated to an increase of 0.034 mm in the CCA
      IMT. CONCLUSION: Systolic ME was associated significantly with CCA-IMT values in
      masked hypertensives. Both normotensive and hypertensive participants have failed
      to show similar associations.

PMID- 25397595
TI  - Sediment composition influences spatial variation in the abundance of human
      pathogen indicator bacteria within an estuarine environment.
AB  - Faecal contamination of estuarine and coastal waters can pose a risk to human
      health, particularly in areas used for shellfish production or recreation.
      Routine microbiological water quality testing highlights areas of faecal
      indicator bacteria (FIB) contamination within the water column, but fails to
      consider the abundance of FIB in sediments, which under certain hydrodynamic
      conditions can become resuspended. Sediments can enhance the survival of FIB in
      estuarine environments, but the influence of sediment composition on the ecology
      and abundance of FIB is poorly understood. To determine the relationship between
      sediment composition (grain size and organic matter) and the abundance of
      pathogen indicator bacteria (PIB), sediments were collected from four transverse
      transects of the Conwy estuary, UK. The abundance of culturable Escherichia coli,
      total coliforms, enterococci, Campylobacter, Salmonella and Vibrio spp. in
      sediments was determined in relation to sediment grain size, organic matter
      content, salinity, depth and temperature. Sediments that contained higher
      proportions of silt and/or clay and associated organic matter content showed
      significant positive correlations with the abundance of PIB. Furthermore, the
      abundance of each bacterial group was positively correlated with the presence of
      all other groups enumerated. Campylobacter spp. were not isolated from estuarine
      sediments. Comparisons of the number of culturable E. coli, total coliforms and
      Vibrio spp. in sediments and the water column revealed that their abundance was
      281, 433 and 58-fold greater in sediments (colony forming units (CFU)/100g) when
      compared with the water column (CFU/100ml), respectively. These data provide
      important insights into sediment compositions that promote the abundance of PIB
      in estuarine environments, with important implications for the modelling and
      prediction of public health risk based on sediment resuspension and transport. 

PMID- 25397596
TI  - Caveolin-1 limits the contribution of BKCa channel to MCF-7 breast cancer cell
      proliferation and invasion.
AB  - Increasing evidence suggests that caveolin-1 and large conductance Ca2+-activated
      potassium (BKCa) channels are implicated in the carcinogenesis processes,
      including cell proliferation and invasion. These two proteins have been proven to
      interact with each other in vascular endothelial and smooth muscle cells and
      modulate vascular contractility. In this study, we investigated the probable
      interaction between caveolin-1 and BKCa in MCF-7 breast cancer cells. We
      identified that caveolin-1 and BKCa were co-localized and could be reciprocally
      co-immunoprecipitated in human breast cancer MCF-7 cells. siRNA mediated caveolin
      1 knockdown resulted in activation and increased surface expression of BKCa
      channel, and subsequently promoted the proliferation and invasiveness of breast
      cancer cells. These effects were attenuated in the presence of BKCa-siRNA.
      Conversely, up-regulated caveolin-1 suppressed function and surface expression of
      BKCa channel and exerted negative effects on breast cancer cell proliferation and
      invasion. Similarly, these opposing effects were abrogated by BKCa up-regulation.
      Collectively, our findings suggest that BKCa is a critical target for suppression
      by caveolin-1 in suppressing proliferation and invasion of breast cancer cells.
      The functional complex of caveolin-1 and BKCa in the membrane microdomain may be
      served as a potential therapeutic target in breast cancer.

PMID- 25397597
TI  - Synthesis and biological evaluation of 2-thioxopyrimidin-4(1H)-one derivatives as
      potential non-nucleoside HIV-1 reverse transcriptase inhibitors.
AB  - A series of new 5-allyl-6-benzylpyrimidin-4(3H)-ones bearing different
      substituents at the C-2 position of the pyrimidine core have been synthesized and
      evaluated for their in vitro activities against human immunodeficiency virus type
      1 (HIV-1) in the human T-lymphotropic type (MT-4 cell cultures). The majority of
      the title compounds showed moderate to good activities against HIV-1. Amongst
      them, 5-allyl-6-benzyl-2-(3-hydroxypropylthio)pyrimidin-4(3H)-one analogue 11c
      exhibited the most potent anti-HIV-1 activity (IC50 0.32 uM). The biological
      testing results clearly indicated that the substitution at C-2 position of the
      pyrimidine ring could increase the anti-HIV-1 reverse transcriptase (RT)
      activity. 

PMID- 25397598
TI  - Structures of the inducer-binding domain of pentachlorophenol-degrading gene
      regulator PcpR from Sphingobium chlorophenolicum.
AB  - PcpR is a LysR-type transcription factor from Sphingobium chlorophenolicum L-1
      that is responsible for the activation of several genes involved in
      polychlorophenol degradation. PcpR responds to several polychlorophenols in vivo.
      Here, we report the crystal structures of the inducer-binding domain of PcpR in
      the apo-form and binary complexes with pentachlorophenol (PCP) and 2,4,6
      trichlorophenol (2,4,6-TCP). Both X-ray crystal structures and isothermal
      titration calorimetry data indicated the association of two PCP molecules per
      PcpR, but only one 2,4,6-TCP molecule. The hydrophobic nature and hydrogen bonds
      of one binding cavity allowed the tight association of both PCP (Kd = 110 nM) and
      2,4,6-TCP (Kd = 22.8 nM). However, the other cavity was unique to PCP with much
      weaker affinity (Kd = 70 MUM) and thus its significance was not clear. Neither
      phenol nor benzoic acid displayed any significant affinity to PcpR, indicating a
      role of chlorine substitution in ligand specificity. When PcpR is compared with
      TcpR, a LysR-type regulator controlling the expression of 2,4,6-trichlorophenol
      degradation in Cupriavidus necator JMP134, most of the residues constituting the
      two inducer-binding cavities of PcpR are different, except for their general
      hydrophobic nature. The finding concurs that PcpR uses various polychlorophenols
      as long as it includes 2,4,6-trichlorophenol, as inducers; whereas TcpR is only
      responsive to 2,4,6-trichlorophenol. 

PMID- 25397599
TI  - Historical model for editor and Office of Research Integrity cooperation in
      handling allegations, investigation, and retraction in a contentious (Abbs) case
      of research misconduct.
AB  - Cooperation between a journal editor and the federal Office of Research Integrity
      (ORI) in addressing investigations of research misconduct, each performing their
      own responsibilities while keeping each other informed of events and evidence,
      can be critical to the professional and regulatory resolution of a case. This
      paper describes the history of one of ORI's most contentious investigations that
      involved falsification of research on Parkinson's disease patients by James Abbs,
      Professor of Neurology, University of Wisconsin, published in the journal
      Neurology, which was handled cooperatively by the authors, who were the chief ORI
      investigator and the Editor-in-Chief of Neurology, respectively. 

PMID- 25397600
TI  - Building a more connected DSMB: better integrating ethics review and safety
      monitoring.
AB  - Data and Safety Monitoring Boards (DSMBs) have become an increasingly common
      feature of clinical trial oversight, yet a paucity of legal or ethical frameworks
      govern these Boards' composition or operation, or their relationship with other
      actors with monitoring responsibilities. This paper argues that prevailing
      structural gaps are impeding harmonized systems for monitoring the ongoing
      ethical acceptability of clinical trials. Particular tensions stem from DSMBs'
      sweeping discretion in deciding whether and when to recommend that a trial should
      be terminated or amended based on safety and efficacy information. This
      discretion becomes especially challenging in light of DSMBs' monopoly over
      emerging trial data, which prevents Institutional Review Boards, sponsors, and
      investigators from participating in certain pivotal and ethically charged
      decisions. To address these disconnects, I advocate for strengthened pre-trial
      and post-trial communication in addition to innovative strategies to support DSMB
      decision making through the life of a trial. 

PMID- 25397601
TI  - Paving the road to negligence: the compensation for research-related injuries in
      Spain.
AB  - The planned reform of the regulation of clinical trials in Spain has reopened the
      debate over how to regulate research-related injuries. Act 29/2006 and Royal
      Decree 223/2004 regulate the insurance of research-related injuries, and they
      include a general clause requiring mandatory insurance and imposing a no-fault
      compensation system; they also contain an exception clause enabling clinical
      trials to be carried out without insurance under some conditions, and an
      exclusion clause excluding compensation when there is no causal connection
      between injuries and a clinical trial. National legislation is under review,
      affecting the requirement of mandatory insurance and paving the road to a
      liability system based on negligence, which will affect the level of protection
      of the persons enrolled in clinical trials because it would not ensure
      compensation. Regulatory texts on individuals' participation as research subjects
      should include not only mandatory insurance, but also a no-fault compensation
      system for cases when voluntary research subjects are injured, irrespective of
      negligence. 

PMID- 25397602
TI  - Letter to the editor: retraction and coauthorship in problematic publication.

PMID- 25397603
TI  - Laparoscopic-assisted drainage of a massive retroperitoneal abscess caused by
      group B Streptococcus.

PMID- 25397604
TI  - Peripheral CD4+ T cell cytokine responses following human challenge and re
      challenge with Campylobacter jejuni.
AB  - Campylobacter jejuni is a leading cause of human gastroenteritis worldwide;
      however, our understanding of the human immune response to C. jejuni infection is
      limited. A previous human challenge model has shown that C. jejuni elicits
      IFNgamma production by peripheral blood mononuclear cells, a response associated
      with protection from clinical disease following re-infection. In this study, we
      investigate T lymphocyte profiles associated with campylobacteriosis using
      specimens from a new human challenge model in which C. jejuni-naive subjects were
      challenged and re-challenged with C. jejuni CG8421. Multiparameter flow cytometry
      was used to investigate T lymphocytes as a source of cytokines, including
      IFNgamma, and to identify cytokine patterns associated with either
      campylobacteriosis or protection from disease. Unexpectedly, all but one subject
      evaluated re-experienced campylobacteriosis after re-challenge. We show that CD4+
      T cells make IFNgamma and other pro-inflammatory cytokines in response to
      infection; however, multifunctional cytokine response patterns were not found.
      Cytokine production from peripheral CD4+ T cells was not enhanced following re
      challenge, which may suggest deletion or tolerance. Evaluation of alternative
      paradigms or models is needed to better understand the immune components of
      protection from campylobacteriosis. 

PMID- 25397606
TI  - Mechanisms Underlying Exaggerated Metaboreflex Activation in Prehypertensive Men.
AB  - PURPOSE: Previously, we found that the pressor response to muscle metaboreflex
      activation is enhanced in prehypertension and associated with peripheral
      vasoconstriction. However, mechanisms underlying this exaggerated response are
      not clear. Therefore, we tested the hypothesis that activation of this reflex is
      augmented owing to increased production of muscle metabolites (i.e., lactate, K,
      and H). METHODS: Twenty-two men (11 normotensive and 11 prehypertensive) were
      studied. Changes in cardiac output (Q), mean arterial pressure (MAP), and total
      peripheral resistance (TPR) were compared between the two groups during static
      exercise (SE) and postexercise muscular ischemia (PEMI). Subjects completed 2 min
      of SE at 50% of maximal voluntary contraction (MVC) followed by 2 min of PEMI.
      Venous blood samples for determination of metabolites and hormones
      (catecholamines, vasopressin, and plasma renin activity) were taken from the
      exercising and nonexercising arm, respectively. RESULTS: Mean arterial pressure
      responses to SE (39 +/- 3 vs 31 +/- 2 mm Hg) and PEMI (24 +/- 3 vs 19 +/- 3 mm
      Hg) were significantly higher in the prehypertensive group. Increases in lactate
      and decreases in pH during PEMI were seen in both groups. However, changes in
      these variables were greater in the prehypertensive group (lactate, 50.1 +/- 6.2
      vs 32.8 +/- 7.6 mg.dL; pH, -0.06 +/- 0.02 vs -0.01 +/- 0.01) (P < 0.05).
      Postexercise muscular ischemia did not evoke increases in hormones in either
      group. CONCLUSIONS: Compared to the normotensive group, the augmented pressor
      response to the metaboreflex in the prehypertensive group was associated with
      greater production of muscle metabolites that activate its afferent arm. The
      augmented response was not associated with activation of the vasopressin and
      renin-angiotensin systems and greater activation of the sympathetic nervous
      system was not apparent. Consequently, additional factors specific to
      prehypertension, such as arterial stiffness, may have been involved.

PMID- 25397605
TI  - Fractures in Relation to Menstrual Status and Bone Parameters in Young Athletes.
AB  - INTRODUCTION: This study was aimed to compare fracture prevalence in
      oligoamenorrheic athletes (AA), eumenorrheic athletes (EA), and nonathletes (NA)
      and determine relationships with bone density, structure, and strength estimates.
      METHODS: One hundred seventy-five females (100 AA, 35 EA, and 40 NA) 14-25 yr old
      were studied. Lifetime fracture history was obtained through participant
      interviews. Areal bone mineral density (BMD) was assessed by DXA at the spine,
      hip, and whole body (WB). Bone structure was assessed by HRpQCT at the radius and
      tibia, and strength by finite element analysis. RESULTS: AA, EA, and NA did not
      differ in age, sexual maturity, or height. AA had lower BMI, and older menarchal
      age than EA and NA (P <= 0.001). Bone mineral density Z-scores were lower in AA
      versus EA at the total hip, femoral neck, spine, and whole body (P <= 0.001).
      Lifetime fracture risk was higher in AA than EA and NA (47%, 25.7%, 12.5%; P <=
      0.001), largely driven by stress fractures in AA versus EA and NA (32% vs 5.9% vs
      0%). In AA, those who fractured had lower lumbar and WB BMD Z-scores, volumetric
      BMD (vBMD) of outer trabecular region in radius and tibia, and trabecular
      thickness of the radius (P <= 0.05). In AA, those who had two or more stress
      fractures had lower lumbar and WB BMD Z-scores, total cross-sectional area,
      trabecular vBMD, stiffness, and failure load at radius; and lower stiffness and
      failure load at tibia versus those with fewer than two stress fractures (P <=
      0.05). CONCLUSION: Weight-bearing athletic activity increases BMD but may
      increase stress fracture risk in those with menstrual dysfunction. Bone
      microarchitecture and strength differences are more pronounced in AA with
      multiple stress fractures. This is the first study to examine fractures in
      relation to bone structure in adolescent female athletes.

PMID- 25397607
TI  - Do Moments and Strength Predict Cartilage Changes after Partial Meniscectomy?
AB  - PURPOSE: Higher knee load and quadriceps weakness are potential factors involved
      in the pathogenesis of knee osteoarthritis after arthroscopic partial
      meniscectomy (APM). In people following APM, this study evaluated the association
      between external knee joint moments and quadriceps strength and 2-yr change in
      indices of cartilage integrity in the medial tibiofemoral compartment and
      patella. METHODS: Seventy people with medial APM were assessed 3 months after APM
      (baseline) and reassessed 2 yr later (follow-up). At baseline, isokinetic
      quadriceps strength and the external knee adduction moment (peak and impulse) and
      knee flexion moment (peak) during walking were assessed. Magnetic resonance
      imaging was used to assess cartilage (cartilage volume and cartilage defects) in
      the medial tibial compartment and patella at baseline and follow-up. RESULTS:
      Increased peak knee adduction moment during fast-pace walking at baseline was
      associated with onset or deterioration of medial tibiofemoral cartilage defects
      (OR, 2.06; 95% CI, 1.03-4.12; P = 0.042) over 2 yr. Increased peak knee flexion
      moment during normal-pace walking at baseline was associated with loss of
      patellar cartilage volume over 2 yr (beta = -0.24; 95% CI, -0.47 to -0.01; P =
      0.04). No significant association was observed for quadriceps strength.
      CONCLUSION: In middle-age adults, a higher peak knee adduction moment and peak
      knee flexion moment at 3 months after medial APM may be associated with adverse
      structural changes at the medial tibia and patella over the subsequent 2 yr.
      These preliminary findings warrant further investigation as interventions aimed
      at reducing these moments may be designed if appropriate.

PMID- 25397613
TI  - Are breaks in daily self-weighing associated with weight gain?
AB  - Regular self-weighing is linked to successful weight loss and maintenance.
      However, an individual's self-weighing frequency typically varies over time. This
      study examined temporal associations between time differences of consecutive
      weight measurements and the corresponding weight changes by analysing
      longitudinal self-weighing data, including 2,838 weight observations from 40
      individuals attending a health-promoting programme. The relationship between
      temporal weighing frequency and corresponding weight change was studied primarily
      using a linear mixed effects model. Weight change between consecutive weight
      measurements was associated with the corresponding time difference (beta = 0.021%
      per day, p<0.001). Weight loss took place during periods of daily self-weighing,
      whereas breaks longer than one month posed a risk of weight gain. The findings
      emphasize that missing data in weight management studies with a weight-monitoring
      component may be associated with non-adherence to the weight loss programme and
      an early sign of weight gain. 

PMID- 25397608
TI  - Gestational hypertension and preeclampsia in living kidney donors.
AB  - BACKGROUND: Young women wishing to become living kidney donors frequently ask
      whether nephrectomy will affect their future pregnancies. METHODS: We conducted a
      retrospective cohort study of living kidney donors involving 85 women (131
      pregnancies after cohort entry) who were matched in a 1:6 ratio with 510 healthy
      nondonors from the general population (788 pregnancies after cohort entry).
      Kidney donations occurred between 1992 and 2009 in Ontario, Canada, with follow
      up through linked health care databases until March 2013. Donors and nondonors
      were matched with respect to age, year of cohort entry, residency (urban or
      rural), income, number of pregnancies before cohort entry, and the time to the
      first pregnancy after cohort entry. The primary outcome was a hospital diagnosis
      of gestational hypertension or preeclampsia. Secondary outcomes were each
      component of the primary outcome examined separately and other maternal and fetal
      outcomes. RESULTS: Gestational hypertension or preeclampsia was more common among
      living kidney donors than among nondonors (occurring in 15 of 131 pregnancies
      [11%] vs. 38 of 788 pregnancies [5%]; odds ratio for donors, 2.4; 95% confidence
      interval, 1.2 to 5.0; P=0.01). Each component of the primary outcome was also
      more common among donors (odds ratio, 2.5 for gestational hypertension and 2.4
      for preeclampsia). There were no significant differences between donors and
      nondonors with respect to rates of preterm birth (8% and 7%, respectively) or low
      birth weight (6% and 4%, respectively). There were no reports of maternal death,
      stillbirth, or neonatal death among the donors. Most women had uncomplicated
      pregnancies after donation. CONCLUSIONS: Gestational hypertension or preeclampsia
      was more likely to be diagnosed in kidney donors than in matched nondonors with
      similar indicators of baseline health. (Funded by the Canadian Institutes of
      Health Research and others.).

PMID- 25397614
TI  - Magnetic resonance imaging for diagnosis of mandibular involvement from head and
      neck cancers: a systematic review and meta-analysis.
AB  - BACKGROUND: Diagnosis of mandibular involvement caused by head and neck cancers
      is critical for treatment. We performed a meta-analysis to determine the
      diagnostic efficacy of MR for distinguishing mandibular involvement caused by
      head and neck cancers. METHODS: Thirteen databases were searched electronically
      and hand-searching was also done. Two reviewers conducted study inclusion, data
      extractions, and quality assessment of the studies independently. Meta-disc 1.4
      and STATA 11.0 were used to conduct the meta-analysis. RESULTS: 16 studies
      involving a total of 490 participants underwent MR examinations and were
      accounted for in this meta-analysis. Among the included studies, 2 had high risk
      of bias, while the rest had unclear risk of bias. Meta-regression showed that the
      slight clinical and methodological heterogeneities did not influence the outcome
      (P>0.05). Meta-analysis indicated that the MR for the diagnosis of mandibular
      involvement had a pooled sensitivity (SEN) of 78%, specificity (SPE) of 83%,
      positive likelihood ratio (+LR) of 3.80, negative likelihood ratio (-LR) of 0.28,
      diagnostic odds ratio (DOR) of 28.94, area under curve (AUC) of 0.9110, and Q* of
      0.8432. Two studies detected the diagnostic efficacy of MR for the mandibular
      medullar invasion, and only one study reported the inferior alveolar canal
      invasion, which made it impossible to include it in our meta-analysis. In
      comparing to CT, MR had a higher SEN without statistical significance (P = 0.08),
      but a significantly lower SPE (P = 0.04). The synthesized diagnostic efficacy
      (AUC and Q*) on mandibular involvement was similar between the two modalities
      (P>0.05). CONCLUSIONS: Present clinical evidence showed that MR had an acceptable
      diagnostic value in detecting mandibular involvement caused by head and neck
      cancers. MR exceeded CT in diagnosing patients with mandibular invasion (higher
      sensitivity than CT) but was less efficacious to exclude patients without the
      mandibular invasion (lower specificity than CT).

PMID- 25397615
TI  - Pay dispersion and performance in teams.
AB  - Extant research offers conflicting predictions about the effect of pay dispersion
      on team performance. We collected a unique dataset from the Italian soccer league
      to study the effect of intra-firm pay dispersion on team performance, under
      different definitions of what constitutes a "team". This peculiarity of our
      dataset can explain the conflicting evidence. Indeed, we also find positive,
      null, and negative effects of pay dispersion on team performance, using the same
      data but different definitions of team. Our results show that when the team is
      considered to consist of only the members who directly contribute to the outcome,
      high pay dispersion has a detrimental impact on team performance. Enlarging the
      definition of the team causes this effect to disappear or even change direction.
      Finally, we find that the detrimental effect of pay dispersion is due to worse
      individual performance, rather than a reduction of team cooperation. 

PMID- 25397616
TI  - HIV cure strategies: how good must they be to improve on current antiretroviral
      therapy?
AB  - BACKGROUND: We examined efficacy, toxicity, relapse, cost, and quality-of-life
      thresholds of hypothetical HIV cure interventions that would make them cost
      effective compared to life-long antiretroviral therapy (ART). METHODS: We used a
      computer simulation model to assess three HIV cure strategies: Gene Therapy,
      Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy
      and cost parameters were varied widely in sensitivity analysis. Outcomes included
      quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in
      dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost
      effective with incremental cost-effectiveness ratios <$100,000/QALY. RESULTS: For
      patients on ART, discounted quality-adjusted life expectancy was 16.4 years and
      lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of
      10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective
      with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24
      months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and
      relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made
      Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to
      make Chemotherapy or SCT cost-saving. CONCLUSIONS: Depending on efficacy, relapse
      rate, and cost, cure strategies could be cost-effective compared to current ART
      and potentially cost-saving. These results may help provide performance targets
      for developing cure strategies for HIV.

PMID- 25397618
TI  - 'Chrysanthemum petal' arrangements of silver nano wires.
AB  - Highly ordered 'Chrysanthemum petal' arrangements of silver nano wires were
      fabricated in a biodegradable polymer of polyvinyl alcohol using a simple one
      step blending method without any template. The degree of the arrangement
      increased with the decreasing content of polyvinyl alcohol. The mechanism for the
      formation of these 'Chrysanthemum petal' arrangements was discussed specifically.
      These 'Chrysanthemum petal' arrangements will be helpful to increase the
      electrical conductivity of silver nano wires films. 

PMID- 25397617
TI  - Primary murine CD4+ T cells fail to acquire the ability to produce effector
      cytokines when active Ras is present during Th1/Th2 differentiation.
AB  - Constitutive Ras signaling has been shown to augment IL-2 production, reverse
      anergy, and functionally replace many aspects of CD28 co-stimulation in CD4+ T
      cells. These data raise the possibility that introduction of active Ras into
      primary T cells might result in improved functionality in pathologic situations
      of T cell dysfunction, such as cancer or chronic viral infection. To test the
      biologic effects of active Ras in primary T cells, CD4+ T cells from Coxsackie
      Adenovirus Receptor Transgenic mice were transduced with an adenovirus encoding
      active Ras. As expected, active Ras augmented IL-2 production in naive CD4+ T
      cells. However, when cells were cultured for 4 days under conditions to promote
      effector cell differentiation, active Ras inhibited the ability of CD4+ T cells
      to acquire a Th1 or Th2 effector cytokine profile. This differentiation defect
      was not due to deficient STAT4 or STAT6 activation by IL-12 or IL-4,
      respectively, nor was it associated with deficient induction of T-bet and GATA-3
      expression. Impaired effector cytokine production in active Ras-transduced cells
      was associated with deficient demethylation of the IL-4 gene locus. Our results
      indicate that, despite augmenting acute activation of naive T cells, constitutive
      Ras signaling inhibits the ability of CD4+ T cells to properly differentiate into
      Th1/Th2 effector cytokine-producing cells, in part by interfering with epigenetic
      modification of effector gene loci. Alternative strategies to potentiate Ras
      pathway signaling in T cells in a more regulated fashion should be considered as
      a therapeutic approach to improve immune responses in vivo. 

PMID- 25397619
TI  - Ofatumumab and high-dose methylprednisolone for the treatment of patients with
      relapsed or refractory chronic lymphocytic leukemia.
AB  - Ofatumumab is a humanized anti-CD20 monoclonal antibody that has been approved by
      the FDA for the treatment of patients with chronic lymphocytic leukemia. We
      conducted a phase II single-arm study at a single center. Patients received
      ofatumumab (300 mg then 1000 mg weekly for 12 weeks) and methylprednisolone (1000
      mg/m(2) for 3 days of each 28-day cycle). Twenty-one patients enrolled, including
      29% with unfavorable cytogenetics (del17p or del11q). Ninety percent of patients
      received the full course without dose reductions or delays. The overall response
      rate was 81% (17/21) with 5% complete response, 10% nodular partial response, 67%
      partial response, 14% stable disease and 5% progressive disease. After a median
      follow-up of 31 months, the median progression-free survival was 9.9 months and
      the median time to next treatment was 12.1 months. The median overall survival
      has not yet been reached. The combination of high-dose methylprednisolone and
      ofatumumab is an effective and tolerable treatment regimen. This regimen may be
      useful for patients who are unable to tolerate more aggressive therapies, or have
      not responded to other treatments.

PMID- 25397620
TI  - Medical practice in the ancient Asclepeion in Kos island.
AB  - Asclepius was called "a great doctor for every disease". Asclepius was born in
      Trikala, Thessaly, in the middle of Greece, where the first Asclepeion was
      established. Patients coming to the Asclepeia were first taking cleaning baths
      and then entered the main Asclepeion, where they were examined by priests
      therapists and were accommodated in certain areas-rooms of the Asclepeion.
      Inscriptions found in marble plaques describe treatment of some diseases and the
      sum of money paid for every treatment. These were the first medical records and
      fees in ancient Greece. Patients were considered as a unique psychosomatic
      entity. Patients followed many instructions in order to relax and rest, submitted
      daily baths, exercises, massages, entertainment attending theatrical or poetic or
      athletic races, reading special books, promenades, special diets or were kept
      fasting and were instructed to take many kinds of medicine per os, suppositories,
      ointments, eye drops etc. The main diseases treated in the Asclepeia were:
      chronic neuropsychological disorders, skin diseases and chronic lung diseases.
      Other diseases gynaecological, ophthalmic and surgical were also treated. Today,
      like in the ancient Asclepeia, the psychology of patients is important and
      certain preparatory drugs are administered before the actual main treatment of
      surgery or of some psychic disorders. In Aalborg, Denmark, a large prototype
      medical university hospital, is scheduled to be built in an area of 350acres
      within the next 15 years. The psychosomatic dogma and principals of a "green
      building" will be well respected. The Asclepeion of the island of Kos, where as
      we know Hippocrates was born, was built on the 5th century B.C. and functioned
      till the 4th century A.D. and had three floors. The Asclepeion had many
      dedications, of which many parts of the human body in marble: an ear, a damaged
      penis and two breasts. Surgical tools were also found and are now exhibited in
      the Dion Museum. After the 4th century A.D. the Asclepeion was destructed and/or
      destroyed by religious groups, more earthquakes, conflagrations, the Saint John's
      Knights of Jerusalem and the Turks. Recent excavations in the area in order to
      find and restore the old Asclepeion started in 1902. Now Asclepeion is partly
      restored. In conclusion, it is suggested that Hippocratic medicine, as practiced
      in the Asclepeion of the island of Kos, using psychosomatic means of treatment in
      a green natural environment was effective for many diseases at that time but also
      inspired modern medicine and as an example a large university institution is now
      under constructions based on the above ideals. 

PMID- 25397621
TI  - Focal tracer uptake in the jaw.
AB  - Focal tracer uptake in the jaw during conventional bone scintigraphy is a quite
      frequent finding usually due to dental disease and seldom to other diseases
      including malignant disease. Methylene diphosphonate-technetium-99m ((99m)Tc-MDP)
      3-phase bone scan is considered the most sensitive imaging method for the
      detection of jaw osteonecrosis at an early stage. This finding can also but
      seldom be seen in patients undergoing palliative radionuclide treatment for bone
      metastases. In conclusion, focal jaw lesions are usually benign and of dental
      origin. In a small percentage of cancer patients of about 4.3%, jaw lesions as
      diagnosed among 347 cases of various carcinomas may be due to malignancy.
      Unfortunately, the number of studies is small, most of them are retrospective and
      few show biopsy results. 

PMID- 25397622
TI  - Initial experience of integrated PET/MR mammography in patients with invasive
      ductal carcinoma.
AB  - The purpose of this study was to evaluate the feasibility of integrated fluorine
      18-fluorodeoxyglucose positron emission tomography/magnetic resonance ((18)F-FDG
      PET/MR) mammography in invasive ductal carcinoma (IDC) patients. From August 2012
      to March 2013, we enrolled 42 consecutive breast cancer patients who received
      whole- body PET/MR and subsequent PET/MR mammography by an integrated PET/MR
      scanner and were scheduled for surgery within 2 weeks after the of scan. On the
      whole body PET/MR, 2-point Dixon VIBE, coronal T1w image, axial T2w image, and
      post-contrast T1 sequences were acquired with simultaneous PET acquisition. For
      PET/MR mammography, T1w, T2w, and dynamic contrast-enhancement (DCE) sequences
      were acquired using a breast coil during simultaneous PET acquisition. We
      compared the detectability of the lesions between whole-body PET/MR and PET/MR
      mammography. Forty-eight IDC (1.89+/-1.19cm of width) were diagnosed in 42 women.
      Lesion conspicuity in (18)F-FDG PET was equivalent between whole-body PET/MR and
      PET/MR mammography; both PET/MR images showed 38 hypermetabolic masses. In the
      analysis of 10 IDC with <1.0cm wide lesions, only 1 IDC showed (18)F-FDG uptake,
      and 4 IDC were noted on whole-body PET/MR; however, all 10 IDC showed a
      depictable mass on PET/MR mammography. In the analysis of 38 IDC >1.0cm wide, 37
      IDC showed (18)F-FDG uptake, and 38 IDC were detected on both whole-body PET/MR
      and PET/MR mammography. The overall sensitivity was 79.2% (38/48) on PET, 87.5%
      (42/48) on whole-body PET/MR, and 100% on PET/MR mammography. The SUV between
      whole-body PET/MR and PET/MR mammography showed strong and highly significant
      correlation (r=0.987, P<0.001). In conclusion, our results, although in a limited
      number of cases show that integrated PET/MR mammography is feasible and has the
      advantage of combining high-resolution breast images with metabolic images.
      Furthermore, PET/MR mammography could provide an accurate diagnosis in case of
      IDC that are less than 1cm in size. 

PMID- 25397623
TI  - Sentinel lymph node detection in vulvar cancer patients: a 20 years analysis.
AB  - Our study aimed to analyze postoperative treatment-related morbidity after
      sentinel lymph node biopsy (SLNB) compared to systematic inguinofemoral lymph
      node dissection (ILND) and the recurrence rate in patients with vulvar cancer.
      This single center study included 128 patients diagnosed with vulvar cancer that
      underwent ILND or SLNB between January 1991 - January 2011 with intraoperative
      SLN detection and removal. Treatment-related morbidity, as well as recurrence
      rate of SLNB patients were evaluated. Preoperative sentinel node scintigraphy was
      successful in 82/89 (92%) of the patients. A hundred and seventy six nodes were
      visualized and all positive SLN were detected within 60min. Patients who were
      treated with ILND underwent a longer operation (P<0.001), required longer
      inguinal drainage (P<0.001), and had a lengthier postoperative hospital stay
      (P=0.006). The presence of lymph cysts (P=0.02, 95% CI 3.4 (1-1-10.6) was
      significantly higher in ILND patients. No groin recurrence was appreciated in
      SLNB patients. In conclusion, patients who underwent SLNB were at a lower risk of
      postoperative morbidity. No groin recurrences were observed in patients who
      received SLNB. 

PMID- 25397624
TI  - The effect of antiallergic treatment with desloratadine-montelukast on salivary
      glands function in allergic rhinitis.
AB  - The aim of this study was to evaluate the possible favorable effect of
      desloratadine-montelukast combination on salivary glands (SG) function in
      patients with allergic rhinitis (AR) using SG scintigraphy. The study population
      consisted of 64 patients with AR and 28 healthy controls: 14 males and 14
      females, with mean age 32.3+/-8.6 years. The patients were divided into two
      groups: the untreated patients group of 32 patients, 16 males and 16 females,
      mean age 28.5+/-5.4 years and the treated group, who received the standard
      clinically recommended oral dose of montelukast 10mg/d and desloratadine 5mg/d
      for 6 weeks. This group consisted of 32 patients, 16 males and 16 females, mean
      age 38.3+/-8.4 years. All patients and healthy controls underwent SG
      scintigraphy. After the intravenous injection of technetium-99m pertechnetate,
      ((99m)Tc-P), dynamic SG scintigraphy was performed for 25min. Using the time
      activity curves, the following glandular function parameters were calculated for
      the parotid and the submandibular SG: uptake ratio, maximum accumulation and
      ejection fraction. Results showed SG hypofunction. All functional parameters
      obtained for the untreated patients and for the desloratadine-montelukast treated
      patients were significantly lower than those in healthy controls (P<0.05). There
      was no statistically significant difference between treated and untreated
      patients (P>0.05). In conclusion, our study showed that hypofunction of SG was
      present in all patients with AR. This hypofunction, as tested by semi
      quantitative SG scintigraphy, and also the quality of life did not improve after
      treatment with montelukast and desloratadine. 

PMID- 25397625
TI  - Phantom studies and clinical application of high resolution, image reconstruction
      using (18)F-fluoromethylcholine PET/CT for prostate cancer.
AB  - The aim of this study is to evaluate the impact of a high resolution (HR) image
      reconstruction with a voxel size of 2mm in comparison to the most routinely used
      standard reconstruction with 4mm voxels in patients suffering from prostate
      cancer having undergone (18)F-methylcholine PET/CT. Phantom studies were
      performed using a Jaszczak phantom and a custom made phantom containing small hot
      lesions (size 2-10mm). Clinical evaluation was performed on PET/CT scans of 50
      patients. Images were reconstructed with 4mm and 2mm voxel size and analyzed
      quantitatively using AMIDE and MATLAB. Clinical images were judged by two
      observers concerning TNM staging, image quality and the correlation of PET and CT
      data. Phantom studies revealed increased SUVmean and SUVmax values in the HR
      images (P<0.01). The lower detection limit was approximately 3mm in the HR and 4
      5mm in the conventional images. Lower FWHM values were found in the HR images. No
      significant difference was found concerning the image quality and the correlation
      of PET and CT (each P>0.5). For both reconstructions, a comparable total amount
      of lesions was reported (P>0.5) with no impact on the TNM staging. In conclusion,
      the HR PET reconstruction provides semi-quantitative advantages in the sense of
      an improved lower detection limit and increased semi-quantitative tumour-to
      background ratios. In the setting of choline PET/CT for prostate cancer the high
      resolution reconstruction could be implemented clinically as there are no
      relevant qualitative differences between this and the conventional image
      resolution in terms of image quality, assessment confidence and lesion
      identification rate. 

PMID- 25397626
TI  - Incidental detection of increased (18)F-FDG uptake and its follow-up in patients
      with granulomatous prostatitis after BCG treatment for urinary bladder cancer.
AB  - Incidental prostate uptake of fluorine-18-fluorodeoxyglucose in positron emission
      tomography/computed tomography ((18)F-FDG PET/CT) may represent malignancies like
      prostate malignancy, inflammation or benign prostatic lesions. We report two
      cases of bacillus Calmette-Guerin (BCG)-induced granulomatous prostatitis that
      showed (18)F-FDG uptake of the prostate gland on (18)F-FDG PET/CT in patients who
      had previously received intravesical BCG treatment for bladder cancer. The degree
      of (18)F-FDG uptake was decreased on the follow-up PET/CT scan after one year,
      without any specific treatment. 

PMID- 25397627
TI  - Differential diagnosis between secondary and tertiary hyperparathyroidism in a
      case of a giant-cell and brown tumor containing mass. Findings by (99m)Tc-MDP,
      (18)F-FDG PET/CT and (99m)Tc-MIBI scans.
AB  - Brown tumor is one of the skeletal manifestations of hyperparathyroidism. It is a
      benign but locally aggressive bone lesion and its differential diagnosis with
      giant cell containing skeletal tumors or metastases may be complicated. We
      present a male patient with chronic renal failure who was initially misdiagnosed
      as having a giant-cell rich neoplasm of bone in his right thumb. Diffusely
      increased fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the axial and
      appendicular skeleton and multiple (18)F-FDG avid lytic lesions suggesting
      multiple metastases were observed on the (18)F-FDG positron emission
      tomography/computed tomography (PET/CT) scan. On the usual technetium-99m
      methylene diphosphonate ((99m)Tc-MDP) bone scan we noticed diffusely increased
      uptake in the skeleton and two focuses with very much increased uptake, which
      suggested a metabolic bone disease rather than a multiple metastatic giant cell
      tumor or bone metastases. Additional investigation documentated increased levels
      of parathyroid hormone. Parathyroid hyperplasia was finally diagnosed with
      (99m)Tc-methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy. Fluorine-18
      FDG avid lytic lesions were attributed to hyerparathyroidism associated brown
      tumors instead of multiple metastases. In conclusion, we present a patient with
      chronic renal insufficiency, who suffered from secondary and later from tertiary
      HPT with polyostotic brown tumors, which were best shown by the (18)F-FDG PET/CT
      than by the (99m)Tc-MDP or the (99m)Tc-MIBI scans. 

PMID- 25397628
TI  - Scintigraphic perfusion defects due to right ventricular apical pacing: a pitfall
      in clinical cardiology.
AB  - Right ventricular apical pacing (RVAP) with a left bundle branch block on the
      electrocardiogram may result in regional wall motion abnormalities and decreased
      left ventricular function (LVF). Furthermore, perfusion defects in dipyridamole
      technetium-99m-methoxisobutylisonitrile ((99m)Tc-MIBI) myocardial perfusion
      imaging may occur despite a normal coronary angiogram. In a 68 years old patient,
      RVAP resulted in regional wall motion abnormalities, markedly decreased LVF and
      perfusion defects in dipyridamole (99m)Tc-MIBI myocardial perfusion imaging by
      single photon emission tomography (SPET). Coronary angiography excluded coronary
      heart disease. Reprogramming of the pacemaker resulted in physiologic activation
      of the ventricles. Echocardiography showed a normal LV systolic function.
      Repeated myocardial perfusion imaging was unremarkable. In conclusion, our case
      confirms thatRVAP may lead to scintigraphic perfusion defects and wall motion
      abnormalities despite a normal coronary angiogram and this differentiate between
      ischemia-induced perfusion defects. 

PMID- 25397629
TI  - Evaluation of the therapeutic response by (99m)Tc-ECD-SPET in a female with non
      organic depression, generalized anxiety and heterophobia.
AB  - This is the case of a 33 years old female patient who was diagnosed with
      depression and heterophobia, which progressed to generalized anxiety according to
      the International Statistical Classification of Diseases and Health Related
      Problems, 10th Revision (ICD-10), Version for 2010 diagnostic criteria. The
      clinical symptoms of the patient were significantly improved after effective
      treatment. The patient underwent before and after treatment 99mTc-ethyl
      cysteinate dimmer ((99m)Tc-ECD) brain single-photon emission tomography (SPET). A
      great improvement in regional cerebral blood flow was found after treatment. In
      conclusion, this case highlights the value of brain perfusion SPET scan in
      providing objective imaging evidence of diagnosis and treatment evaluation in a
      patient with non-organic mental disorder. 

PMID- 25397630
TI  - [Nuclear Medicine in diagnosis of breast cancer].
AB  - Breast cancer is the most common malignancy among women worldwide, creating a
      significant need for improved imaging modalities. The advantage of molecular
      imaging over other imaging methods, as confirmed by clinical experience, is the
      ability of providing functional information. This process is achieved by labeling
      a biomarker with an isotope of choice. Therefore imaging methods such as
      scintimammography (SM), (18)F-fluorodeoxyglucose-Positron Emission
      Tomography/Computed Tomography ((18)F-FDG PET/CT), positron emission mammography
      (PEM), lymphoscintigraphy, have proved to be extremely efficient compared to
      morphological imaging of anatomical lesions, as they allow the diagnosis,
      staging, assessment of therapeutic efficacy and patient monitoring to contribute
      as much as possible to improve the prognosis. The development of new
      radiopharmaceuticals in PET imaging, allowing the visualization and
      quantification of biomarkers, such as (18)F-fluoro-17-estradiol, which is bound
      by the estrogen receptors (ER), (18)F-fluoro-l-thymidine (FLT) which is a marker
      of cell proliferation, (18)F-fluoromisonidazole (FISO) a marker of tumor hypoxia
      and angiogenesis markers such as (18)F-fluoroazomycinarabinoside, may give us
      additional information on the characteristics and progress of the disease and
      allow the conduct of targeted therapy. Radioimmunoassay (RIA) using monoclonal
      antibodies in order to recognize serum markers such as CA 15.3, CEA, cytokeratins
      TPA, TPS and Cyfra 21.1, are necessary in the diagnosis of a possible recurrence
      of the disease as well as the degree of response to treatment. Modern research
      focusing on the development of new specific functional breast imaging methods
      improves diagnostic and therapeutic management of patients with breast cancer. 

PMID- 25397631
TI  - Raising the bar for self-reported health status.

PMID- 25397632
TI  - Fe65 Ser228 is phosphorylated by ATM/ATR and inhibits Fe65-APP-mediated gene
      transcription.
AB  - Fe65 binds the amyloid precursor protein (APP) and regulates the secretase
      mediated processing of APP into several proteolytic fragments, including amyloid
      beta-peptides (Abeta) and APP intracellular domain (AICD). Abeta accumulation in
      neural plaques is a pathological feature of Alzheimer's disease (AD) and AICD has
      important roles in the regulation of gene transcription (in complex with Fe65).
      It is therefore important to understand how Fe65 is regulated and how this
      contributes to the function and/or processing of APP. Studies have also
      implicated Fe65 in the cellular DNA damage response with knockout mice showing
      increased DNA strand breaks and Fe65 demonstrating a gel mobility shift after DNA
      damage, consistent with protein phosphorylation. In the present study, we
      identified Fe65 Ser(228) as a novel target of the ATM (ataxia telangiectasia
      mutated) and ATR (ataxia-telangiectasia- and Rad3-related protein) protein
      kinases, in a reaction that occurred independently of APP. Neither
      phosphorylation nor mutation of Ser(228) affected the Fe65-APP complex, though
      this was markedly decreased after UV treatment, with a concomitant decrease in
      the protein levels of APP in cells. Finally, mutation of Ser(228) to alanine
      (thus blocking phosphorylation) caused a significant increase in Fe65-APP
      transcriptional activity, whereas phosphomimetic mutants (S(228)D and S(228)E)
      showed decreased transcriptional activity. These studies identify a novel
      phosphorylation site within Fe65 and a novel regulatory mechanism for the
      transcriptional activity of the Fe65-APP complex.

PMID- 25397634
TI  - Outgoing Editor-in-Chief comments.

PMID- 25397633
TI  - Integration of professional judgement and decision-making in high-level adventure
      sports coaching practice.
AB  - This study examined the integration of professional judgement and decision-making
      processes in adventure sports coaching. The study utilised a thematic analysis
      approach to investigate the decision-making practices of a sample of high-level
      adventure sports coaches over a series of sessions. Results revealed that, in
      order to make judgements and decisions in practice, expert coaches employ a range
      of practical and pedagogic management strategies to create and opportunistically
      use time for decision-making. These approaches include span of control and time
      management strategies to facilitate the decision-making process regarding risk
      management, venue selection, aims, objectives, session content, and
      differentiation of the coaching process. The implication for coaches, coach
      education, and accreditation is the recognition and training of the approaches
      that "create time" for the judgements in practice, namely "creating space to
      think". The paper concludes by offering a template for a more expertise-focused
      progression in adventure sports coaching.

PMID- 25397635
TI  - Predictors of research use among staff in aboriginal addiction treatment programs
      serving women.
AB  - The objective of this study was to identify the predictors of research use among
      staff from Aboriginal addiction programs serving women. A total of 89 staff from
      26 Aboriginal addiction programs completed an online survey that included items
      assessing the theory of planned behavior constructs (attitudes, subjective norms,
      perceived behavioral control), intent to use research, and research use.
      Consistent with the theory of planned behavior, research use was predicted by
      attitudes, subjective norms, and perceived behavioral control. Intent to use
      research was not a mediator, demonstrating partial applicability of the theory of
      planned behavior to staff in Aboriginal addiction programs serving women.

PMID- 25397636
TI  - Racial/ethnic differences in the relationship among cigarette use, religiosity,
      and social norms for U.S. adolescents.
AB  - This study investigated the racial/ethnic differences in the role of social norms
      in the protective relationship between religiosity and cigarette smoking. The
      2009 National Survey on Drug Use and Health was used to investigate the
      relationships between smoking, religiosity, and social norms of U.S. adolescents
      (N = 13,278). Significant indirect effects between religiosity and smoking were
      found through social norms for non-Hispanic White adolescents. Findings were
      mixed for non-Hispanic Black adolescents. Mechanisms driving the religiosity
      smoking association differ across subpopulations. Smoking prevention efforts and
      messaging campaigns that include partnerships with religious communities may
      require consideration of these racial/ethnic differences when planning prevention
      strategies.

PMID- 25397637
TI  - Strategies employed by inner-city activists to reduce alcohol-related problems
      and advance social justice.
AB  - This study explored strategies employed by activists engaged in efforts to change
      policies and laws related to selling and promoting alcoholic beverages based on
      in-depth interviews with 184 social activists in seven U.S. major cities. Nine
      strategies aimed at improving local conditions and influencing policy were
      described by activists across regional contexts. Grassroots mobilization was
      central to all other strategies, which included the creation or enforcement of
      laws, meeting with elected officials, media advocacy, working with police/law
      enforcement, education and training, direct action, changing community norms, and
      negotiating with store owners.

PMID- 25397638
TI  - Adolescent perceptions of alcohol risk: variation by sex, race, student activity
      levels and parental communication.
AB  - Drawing on data gathered from adolescents (N = 18,991) in the 2011 National
      Survey on Drug Use and Health (NSDUH), this study examined the effects of sex and
      race, as well as measures of student activity levels and frequency of recognition
      from parents, on perceptions of the risks associated with binge drinking.
      Overall, female, Black, Asian, and Hispanic adolescents, as well as individuals
      who indicated belonging to more than one race, perceived higher levels of risk.
      Male, White, and Native American/Alaskan/Pacific Islander respondents perceived
      lower risk levels. In addition, those who participated the most in school and
      community activities, as well as those who received more frequent recognition
      from parents, estimated higher levels of risk associated with binge drinking.

PMID- 25397639
TI  - Experiences of and attitudes toward injecting drug use among marginalized African
      migrant and refugee youth in Melbourne, Australia.
AB  - Little is known about injecting drug use (IDU) among people from culturally and
      linguistically diverse backgrounds in Australia. We interviewed 18 young people
      of African ethnicity (6 current/former injectors, 12 never injectors) about
      exposure and attitudes to IDU. Exposure to IDU was common, with IDU characterized
      as unnatural, risky and immoral. IDU was highly stigmatized and hidden from
      family and friends. There is a need for culturally appropriate programs to
      promote open dialogue about substance use to reduce stigma and prevent African
      youth who may use illicit drugs from becoming further marginalized.

PMID- 25397642
TI  - The reliability and validity of the Caregiver Work Limitations Questionnaire.
AB  - OBJECTIVE: To test a new Caregiver Work Limitations Questionnaire (WLQ). On the
      basis of the original WLQ, this new survey instrument assesses the effect of
      caregiving for ill and/or disabled persons on the caregiver's work performance.
      METHOD: A questionnaire was administered anonymously to employees of a large
      business services company. Scale reliability and validity were tested with
      psychometric methods. RESULTS: Of 4128 survey participants, 18.3% currently were
      caregivers, 10.2% were past caregivers, and 71.5% were not caregivers. Current
      caregivers were limited in their ability to perform basic job tasks between mean
      10.3% and 16.8% of the time. Confirmatory factor analysis yielded a scale
      structure similar to the WLQ's. Scales reliabilities (the Cronbach's alpha)
      ranged from 0.91 to 0.95. CONCLUSIONS: The Caregiver WLQ is a new tool for
      understanding the workplace effect of caregiving.

PMID- 25397643
TI  - The impact of HIV-related stigma on older and younger adults living with HIV
      disease: does age matter?
AB  - The purpose of this study was to examine the independent influence of age on
      levels of HIV-related stigma experienced by adults living with HIV/AIDS. To
      accomplish this, cross-sectional data from the Ontario HIV Treatment Network
      Cohort Study were used to determine whether older age is associated with overall
      stigma among HIV-positive adults living in Ontario, Canada (n = 960). The
      relationship was also tested for enacted, anticipated, and internalized stigma.
      Covariates included sociodemographic (e.g., gender, sexual orientation, race) and
      psychosocial variables (e.g., depression). Modifying effects of covariates were
      also investigated. Those 55 and older have significantly lower overall and
      internalized stigma than adults under age 40, even when accounting for gender,
      sexual orientation, income, time since diagnosis, depression, maladaptive coping,
      and social support. Age does not predict enacted or Anticipated Stigma when
      accounting for the demographic and psychosocial variables. A significant
      interaction between depression and age suggests that stigma declines with age
      among those who are depressed but increases to age 50 and then decreases in older
      age groups among those who are not depressed. Age matters when it comes to
      understanding stigma among adults living with HIV/AIDS; however, the relationship
      between age and stigma is complex, varying according to stigma type and
      depression level. 

PMID- 25397640
TI  - Substance use and experienced stigmatization among ethnic minority men who have
      sex with men in the United States.
AB  - Research has documented deleterious effects of racism among ethnic minorities and
      of homophobia among men who have sex with men (MSM). Less is known about the
      impact of multiple forms of stigmatization on ethnic minority MSM. This study
      examined substance use by African American, Asian/Pacific Islander and Latino
      MSM, and the associations of experienced racism and homophobia from various
      sources with polydrug use and stimulant drug use. Experienced racism within the
      general community was associated with higher levels of use; other forms of
      discrimination were either not associated with polydrug or stimulant use or had
      more complex relationships with use. Implications for further research and
      interventions are discussed.

PMID- 25397644
TI  - Religious exemptions in insurance coverage and the patient-clinician
      relationship.

PMID- 25397645
TI  - Interviewing a patient about intimate partner violence.

PMID- 25397646
TI  - A request for "conversion therapy".

PMID- 25397647
TI  - Teen pregnancy and confidentiality.

PMID- 25397648
TI  - 2013 winning essay. Medicine's authority to advocate: responsibilities and
      limitations.

PMID- 25397649
TI  - 2013 runner-up essay. The challenge of physician civic engagement: promoting
      health while preserving public trust.

PMID- 25397650
TI  - Sexual health education in medical school: a comprehensive curriculum.

PMID- 25397651
TI  - Will risk compensation accompany pre-exposure prophylaxis for HIV?

PMID- 25397652
TI  - The decriminalization of sodomy in the United States.

PMID- 25397653
TI  - Medicine, sexual norms, and the role of the DSM.

PMID- 25397654
TI  - Ethical implications of drugs for erectile dysfunction.

PMID- 25397655
TI  - Sexual Sunday school: the DSM and the gatekeeping of morality.

PMID- 25397656
TI  - Is it Groundhog Day?

PMID- 25397657
TI  - Retrospective on the construction and practice of a state-level emergency medical
      rescue team.
AB  - For the past few years, disasters like earthquakes, landslides, mudslides,
      tsunamis, and traffic accidents have occurred with an ever-growing frequency,
      coverage, and intensity greatly beyond the expectation of the public. In order to
      respond effectively to disasters and to reduce casualties and property damage,
      countries around the world have invested more efforts in the theoretical study of
      emergency medicine and the construction of emergency medical rescue forces.
      Consequently, emergency medical rescue teams of all scales and types have come
      into being and have played significant roles in disaster response work. As the
      only state-level emergency medical rescue force from the Chinese People's Armed
      Police Forces, the force described here has developed, through continuous
      learning and practice, a characteristic mode in terms of grouping methods,
      equipment system construction, and training.

PMID- 25397658
TI  - An organizational metamodel for hospital emergency departments.
AB  - I introduce an organizational model describing the response of the hospital
      emergency department. The hybrid simulation/analytical model (called a
      "metamodel") can estimate a hospital's capacity and dynamic response in real time
      and incorporate the influence of damage to structural and nonstructural
      components on the organizational ones. The waiting time is the main parameter of
      response and is used to evaluate the disaster resilience of health care
      facilities. Waiting time behavior is described by using a double exponential
      function and its parameters are calibrated based on simulated data. The metamodel
      covers a large range of hospital configurations and takes into account hospital
      resources in terms of staff and infrastructures, operational efficiency, and the
      possible existence of an emergency plan; maximum capacity; and behavior both in
      saturated and overcapacitated conditions. The sensitivity of the model to
      different arrival rates, hospital configurations, and capacities and the
      technical and organizational policies applied during and before a disaster were
      investigated. This model becomes an important tool in the decision process either
      for the engineering profession or for policy makers.

PMID- 25397659
TI  - American Red Cross Digital Operations Center (DigiDOC): an essential emergency
      management tool for the digital age.
AB  - Social media is becoming the first source of information and also the first way
      to communicate messages. Because social media users will take action based on the
      information they are seeing, it is important that organizations like the Red
      Cross be active in the social space. We describe the American Red Cross's concept
      for a Digital Operations Center (DigiDOC) that we believe should become an
      essential part of all emergency operations centers and a key piece of all
      agencies that operate in disasters. The American Red Cross approach is a
      practical and logical approach that other agencies can use as a model.

PMID- 25397660
TI  - Clinical placements in mental health: a literature review.
AB  - Gaining experience in clinical mental health settings is central to the education
      of health practitioners. To facilitate the ongoing development of knowledge and
      practice in this area, we performed a review of the literature on clinical
      placements in mental health settings. Searches in Academic Search Complete,
      CINAHL, Medline and PsycINFO databases returned 244 records, of which 36 met the
      selection criteria for this review. Five additional papers were obtained through
      scanning the reference lists of those papers included from the initial search.
      The evidence suggests that clinical placements may have multiple benefits (e.g.
      improving students' skills, knowledge, attitudes towards people with mental
      health issues and confidence, as well as reducing their fears and anxieties about
      working in mental health). The location and structure of placements may affect
      outcomes, with mental health placements in non-mental health settings appearing
      to have minimal impact on key outcomes. The availability of clinical placements
      in mental health settings varies considerably among education providers, with
      some students completing their training without undertaking such structured
      clinical experiences. Students have generally reported that their placements in
      mental health settings have been positive and valuable experiences, but have
      raised concerns about the amount of support they received from education
      providers and healthcare staff. Several strategies have been shown to enhance
      clinical placement experiences (e.g. providing students with adequate preparation
      in the classroom, implementing learning contracts and providing clinical
      supervision). Educators and healthcare staff need to work together for the
      betterment of student learning and the healthcare professions. 

PMID- 25397662
TI  - Napping in college students and its relationship with nighttime sleep.
AB  - Abstract. OBJECTIVE: To examine the habit of napping and its relationship with
      nighttime sleep in college students. PARTICIPANTS: Four hundred and forty
      undergraduate students who responded to an anonymous online survey in April 2010.
      METHODS: Three questions were asked to determine the frequency, length, and
      timing of napping during the past month. Sleep quality was measured by the
      Pittsburgh Sleep Quality Index (PSQI). RESULTS: The PSQI score significantly
      differed among self-reported nap-frequency (p=.047) and nap-length (p=.017)
      groups, with those who napped more than 3 times per week and those who napped
      more than 2 hours having the poorest sleep quality. Students who napped between 6
      and 9 pm had shorter sleep on school nights compared with students in other nap
      timing groups (p=.002). CONCLUSIONS: College students who are self-reported
      frequent, long, and late nappers may have a higher risk of poor nighttime sleep
      quality and more severe sleep deprivation.

PMID- 25397663
TI  - Physical Therapists' Perceptions of School-Based Practices.
AB  - AIMS: Surveys have reported that most school-based physical therapists perceive
      ideal practices are not commonly implemented in their settings. Our aim was to
      obtain a more in-depth understanding of these perceptions through open-ended
      inquiry. METHODS: Qualitative data were derived from voluntary open-ended
      responses provided upon completion of a survey regarding school-based physical
      therapy practice. Of the survey's 561 participants, 250 provided open-ended
      commentaries that were analyzed using interpretive phenomenology. RESULTS: Six
      qualitative themes emerged from the open-ended responses, including: In quest:
      Meeting students' school-based needs via physical therapy; Seeking relatedness:
      Finding working teams in the school system; Building understanding: Developing a
      voice/identity in the school context; Stretched beyond limits: Managing
      workloads; Networking: Coordinating services outside school to meet student
      needs; Defying definition: What does working in an educational model mean?
      CONCLUSIONS: School-based physical therapists seek to meet educationally relevant
      physical therapy needs of students, ages 3 to 21 years. Successes appear woven of
      a multitude of factors such as therapist expertise, team dynamics, and district
      supports.

PMID- 25397664
TI  - A Service Delivery Model for Children with DCD Based on Principles of Best
      Practice.
AB  - AIMS: In this perspective article, we propose the Apollo model as an example of
      an innovative interdisciplinary, community-based service delivery model for
      children with Developmental Coordination Disorder (DCD) characterized by the use
      of graduated levels of intensity and evidence-based interventions that focus on
      function and participation. METHODS: We describe the context that led to the
      creation of the Apollo model, describe the approach to service delivery and the
      services offered. RESULTS: The Apollo model has 5 components: first contact,
      service delivery coordination, community-, group-, and individual-interventions.
      This model guided the development of a streamlined set of services offered to
      children with DCD, including early-intake to share educational information with
      families, community interventions, inter-disciplinary and occupational therapy
      groups, and individual interventions. Following implementation of the Apollo
      model, wait-times decreased and the number of children receiving services
      increased, without compromising service quality. CONCLUSIONS: Lessons learned are
      shared to facilitate development of other practice models to support children
      with DCD.

PMID- 25397661
TI  - Exercise-based treatments for substance use disorders: evidence, theory, and
      practicality.
AB  - BACKGROUND: Epidemiological studies reveal that individuals who report risky
      substance use are generally less likely to meet physical activity guidelines
      (with the exception of certain population segments, such as adolescents and
      athletes). A growing body of evidence suggests that individuals with substance
      use disorders (SUDs) are interested in exercising and that they may derive
      benefits from regular exercise, in terms of both general health/fitness and SUD
      recovery. OBJECTIVES: The aims of this paper were to: (i) summarize the research
      examining the effects of exercise-based treatments for SUDs; (ii) discuss the
      theoretical mechanisms and practical reasons for investigating this topic; (iii)
      identify the outstanding relevant research questions that warrant further
      inquiry; and (iv) describe potential implications for practice. METHODS: The
      following databases were searched for peer-reviewed original and review papers on
      the topic of substance use and exercise: PubMed Central, MEDLINE, EMBASE,
      PsycINFO, and CINAHL Plus. Reference lists of these publications were
      subsequently searched for any missed but relevant manuscripts. Identified papers
      were reviewed and summarized by both authors. RESULTS: The limited research
      conducted suggests that exercise may be an effective adjunctive treatment for
      SUDs. In contrast to the scarce intervention trials to date, a relative abundance
      of literature on the theoretical and practical reasons supporting the
      investigation of this topic has been published. CONCLUSIONS: Definitive
      conclusions are difficult to draw due to diverse study protocols and low
      adherence to exercise programs, among other problems. Despite the currently
      limited and inconsistent evidence, numerous theoretical and practical reasons
      support exercise-based treatments for SUDs, including psychological, behavioral,
      neurobiological, nearly universal safety profile, and overall positive health
      effects.

PMID- 25397665
TI  - A Group Motor Skills Program for Children with Coordination Difficulties: Effect
      on Fundamental Movement Skills and Physical Activity Participation.
AB  - AIMS: Children with coordination difficulties are at risk of low levels of
      physical activity (PA) participation. This intervention examined the effects of a
      multidisciplinary program that emphasized parent participation on motor skill
      performance and PA. METHODS: Ten boys (5-7 years) completed a group program
      consisting of conditioning exercises and activities designed to address child
      selected goals. Motor proficiency and PA participation were assessed before and
      after the program using the Test of Gross Motor Development (TGMD-2) and triaxial
      accelerometers, respectively. Rating scales captured child and parent perceptions
      of performance for each child's goals. RESULTS: TGMD-2 subtest raw scores, age
      equivalent and percentile scores improved, along with parent ratings of their
      child's performance. Six children reported skill improvements. On average,
      moderate to vigorous PA improved by 10 min per day although these gains were not
      significant. Time spent in sedentary activities was unchanged. None of the
      children met the Canadian PA and sedentary behaviour guidelines. CONCLUSIONS: The
      results support effectiveness of a group program to improve gross motor
      performance and levels of PA in children with coordination difficulties. Gains in
      both of these domains also have the potential to impact quality of life and
      reduce health risks associated with inactivity.

PMID- 25397666
TI  - Substance abuse, violence, and HIV/AIDS (SAVA) syndemic effects on viral
      suppression among HIV positive women of color.
AB  - The combined epidemics of substance abuse, violence, and HIV/AIDS, known as the
      SAVA syndemic, contribute to the disproportionate burden of disease among people
      of color in the US. To examine the association between HIV viral load suppression
      and SAVA syndemic variables, we used baseline data from 563 HIV+ women of color
      treated at nine HIV medical and ancillary care sites participating in HRSA's
      Special Project of National Significance Women of Color (WOC) Initiative. Just
      under half the women (n=260) were virally suppressed. Five psychosocial factors
      contributing to the SAVA syndemic were examined in this study: substance abuse,
      binge drinking, intimate partner violence, poor mental health, and sexual risk
      taking. Associations among the psychosocial factors were assessed and clustering
      confirmed. A SAVA score was created by summing the dichotomous (present/absent)
      psychosocial measures. Using generalized estimating equation (GEE) models to
      account for site-level clustering and individual-covariates, a higher SAVA score
      (0 to 5) was associated with reduced viral suppression; OR (adjusted)=0.81, 95%
      CI: 0.66, 0.99. The syndemic approach represents a viable framework for
      understanding viral suppression among HIV positive WOC, and suggests the need for
      comprehensive interventions that address the social/environmental contexts of
      patients' lives.

PMID- 25397667
TI  - Semantic interference in picture naming during dual-task performance does not
      vary with reading ability.
AB  - Previous dual-task studies examining the locus of semantic interference of
      distractor words in picture naming have obtained diverging results. In these
      studies, participants manually responded to tones and named pictures while
      ignoring distractor words (picture-word interference, PWI) with varying stimulus
      onset asynchrony (SOA) between tone and PWI stimulus. Whereas some studies
      observed no semantic interference at short SOAs, other studies observed effects
      of similar magnitude at short and long SOAs. The absence of semantic interference
      in some studies may perhaps be due to better reading skill of participants in
      these than in the other studies. According to such a reading-ability account,
      participants' reading skill should be predictive of the magnitude of their
      interference effect at short SOAs. To test this account, we conducted a dual-task
      study with tone discrimination and PWI tasks and measured participants' reading
      ability. The semantic interference effect was of similar magnitude at both short
      and long SOAs. Participants' reading ability was predictive of their naming speed
      but not of their semantic interference effect, contrary to the reading ability
      account. We conclude that the magnitude of semantic interference in picture
      naming during dual-task performance does not depend on reading skill. 

PMID- 25397668
TI  - Assessment of atrial fibrillation and vulnerability in patients with Wolff
      Parkinson-White syndrome using two-dimensional speckle tracking echocardiography.
AB  - PURPOSE: The aim was to assess atrial fibrillation (AF) and vulnerability in
      Wolff-Parkinson-White (WPW) syndrome patients using two-dimensional speckle
      tracking echocardiography (2D-STE). METHODS: All patients were examined via
      transthoracic echocardiography and 2D-STE in order to assess atrial function 7
      days before and 10 days after RF catheter ablation. A postoperative 3-month
      follow-up was performed via outpatient visit or telephone calls. RESULTS: Results
      showed significant differences in both body mass index (BMI) and supraventricular
      tachycardia (SVT) duration between WPW patients and DAVNP patients (both P<0.05).
      Echocardiography revealed that the maximum left atrial volume (LAVmax) and the
      left ventricular mass index (LVMI) in diastole increased noticeably in patients
      with WPW compared to patients with DAVNP both before and after ablation (all
      P<0.05). Before ablation, there were obvious differences in the levels of SRs,
      SRe, and SRa from the 4-chamber view (LA) in the WPW patients group compared with
      patients in the DAVNP group (all P<0.05). In the AF group, there were significant
      differences in the levels of systolic strain rate (SRs), early diastolic strain
      rate (SRe), and late diastolic strain rate (SRa) from the 4-chamber view (LA)
      both before and after ablation (all P<0.05). In the non-AF group, there were
      decreased SRe levels from the 4-chamber view (LA/RA) pre-ablation compared to
      post-ablation (all P<0.05). CONCLUSION: Our findings provide convincing evidence
      that WPW syndrome may result in increased atrial vulnerability and contribute to
      the development of AF. Further, RF catheter ablation of AAV pathway can
      potentially improve atrial function in WPW syndrome patients. Two-dimensional
      speckle tracking echocardiography imaging in WPW patients would be necessary in
      the evaluation and improvement of the overall function of RF catheter ablation in
      a long-term follow-up period.

PMID- 25397669
TI  - Assessing the in situ fertilization status of two marine copepod species, Temora
      longicornis and Eurytemora herdmani; how common are unfertilized eggs in nature?
AB  - We utilized an egg staining technique to measure the in situ fertilization
      success of two marine copepod species, Temora longicornis and Eurytemora herdmani
      from May to October 2008 in coastal Maine and correlated fertilization success
      with environmental conditions in their habitat. T. longicornis is a free spawning
      species that releases eggs into the ambient seawater after mating. In contrast,
      E. herdmani carries eggs in an egg sac until they hatch. The proportion of
      fertilized eggs within E. herdmani egg sacs was significantly higher than the
      freely spawned clutches of T. longicornis. This may be a result of the
      asymmetrical costs associated with carrying vs. spawning unfertilized eggs. T.
      longicornis frequently laid both fertilized and unfertilized eggs within their
      clutch. T. longicornis fertilization was negatively associated with chlorophyll
      concentration and positively associated with population density in their local
      habitat. The fertilization status of E. herdmani egg sacs was high throughout the
      season, but the proportion of ovigerous females was negatively associated with an
      interaction between predators and the proportion of females in the population.
      This study emphasizes that, in addition to population level processes, community
      and ecosystem level processes strongly influence the fertilization success and
      subsequent productivity of copepods. 

PMID- 25397670
TI  - Reduced expression of the polymeric immunoglobulin receptor in pancreatic and
      periampullary adenocarcinoma signifies tumour progression and poor prognosis.
AB  - The polymeric immunoglobulin receptor (pIgR) is a key component of the mucosal
      immune system that mediates epithelial transcytosis of immunoglobulins. High pIgR
      expression has been reported to correlate with a less aggressive tumour phenotype
      and an improved prognosis in several human cancer types. Here, we examined the
      expression and prognostic significance of pIgR in pancreatic and periampullary
      adenocarcinoma. The study cohort encompasses a consecutive series of 175 patients
      surgically treated with pancreaticoduodenectomy for pancreatic and periampullary
      adenocarcinoma in Malmo and Lund University Hospitals, Sweden, between 2001-2011.
      Tissue microarrays were constructed from primary tumours (n = 175) and paired
      lymph node metastases (n = 105). A multiplied score was calculated from the
      fraction and intensity of pIgR staining. Classification and regression tree
      analysis was used to select the prognostic cut-off. Unadjusted and adjusted
      hazard ratios (HR) for death and recurrence within 5 years were calculated. pIgR
      expression could be evaluated in 172/175 (98.3%) primary tumours and in 96/105
      (91.4%) lymph node metastases. pIgR expression was significantly down-regulated
      in lymph node metastases as compared with primary tumours (p = 0.018). Low pIgR
      expression was significantly associated with poor differentiation grade (p <
      0.001), perineural growth (p = 0.027), lymphatic invasion (p = 0.016), vascular
      invasion (p = 0.033) and infiltration of the peripancreatic fat (p = 0.039). In
      the entire cohort, low pIgR expression was significantly associated with an
      impaired 5-year survival (HR = 2.99, 95% confidence interval (CI) 1.71-5.25) and
      early recurrence (HR = 2.89, 95% CI 1.67-4.98). This association remained
      significant for survival after adjustment for conventional clinicopathological
      factors, tumour origin and adjuvant treatment (HR = 1.98, 95% CI 1.10-3.57).
      These results demonstrate, for the first time, that high tumour-specific pIgR
      expression signifies a more favourable tumour phenotype and that low expression
      independently predicts a shorter survival in patients with pancreatic and
      periampullary cancer. The mechanistic basis for the putative tumour suppressing
      properties of pIgR in these cancers merits further study.

PMID- 25397671
TI  - Cell population kinetics of collagen scaffolds in ex vivo oral wound repair.
AB  - Biodegradable collagen scaffolds are used clinically for oral soft tissue
      augmentation to support wound healing. This study sought to provide a novel ex
      vivo model for analyzing healing kinetics and gene expression of primary human
      gingival fibroblasts (hGF) within collagen scaffolds. Sponge type and gel type
      scaffolds with and without platelet-derived growth factor-BB (PDGF) were assessed
      in an hGF containing matrix. Morphology was evaluated with scanning electron
      microscopy, and hGF metabolic activity using MTT. We quantitated the population
      kinetics within the scaffolds based on cell density and distance from the
      scaffold border of DiI-labled hGFs over a two-week observation period. Gene
      expression was evaluated with gene array and qPCR. The sponge type scaffolds
      showed a porous morphology. Absolute cell number and distance was higher in
      sponge type scaffolds when compared to gel type scaffolds, in particular during
      the first week of observation. PDGF incorporated scaffolds increased cell
      numbers, distance, and formazan formation in the MTT assay. Gene expression
      dynamics revealed the induction of key genes associated with the generation of
      oral tissue. DKK1, CYR61, CTGF, TGFBR1 levels were increased and integrin ITGA2
      levels were decreased in the sponge type scaffolds compared to the gel type
      scaffold. The results suggest that this novel model of oral wound healing
      provides insights into population kinetics and gene expression dynamics of
      biodegradable scaffolds. 

PMID- 25397673
TI  - Detection of pneumonia associated pathogens using a prototype multiplexed
      pneumonia test in hospitalized patients with severe pneumonia.
AB  - Severe pneumonia remains an important cause of morbidity and mortality.
      Polymerase chain reaction (PCR) has been shown to be more sensitive than current
      standard microbiological methods--particularly in patients with prior antibiotic
      treatment--and therefore, may improve the accuracy of microbiological diagnosis
      for hospitalized patients with pneumonia. Conventional detection techniques and
      multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were
      performed on respiratory samples collected from adult hospitalized patients
      enrolled in a prospective multi-center study. Patients were enrolled from March
      until September 2012. A total of 739 fresh, native samples were eligible for
      analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276
      pathogens were detected by microbiology for which a valid PCR result was
      generated (positive or negative detection result by Curetis prototype system).
      Among these, 120 were identified by the prototype assay, 50 pathogens were not
      detected. Overall performance of the prototype for pathogen identification was
      70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound:
      76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%).
      Based on the study results, device cut-off settings were adjusted for future
      series production. The overall performance with the settings of the CE series
      production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6%
      specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median)
      for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application
      provides a rapid and moderately sensitive assay for the detection of pneumonia
      causing pathogens with minimal hands-on time. TRIAL REGISTRATION: Deutsches
      Register Klinischer Studien (DRKS) DRKS00005684.

PMID- 25397674
TI  - Analysis of the viscoelastic properties of the human cornea using Scheimpflug
      imaging in inflation experiment of eye globes.
AB  - PURPOSE: To demonstrate a Scheimpflug-based imaging procedure for investigating
      the depth- and time-dependent strain response of the human cornea to inflation
      testing of whole eye globes. METHODS: Six specimens, three of which with intact
      corneal epithelium, were mounted in a customized apparatus within a humidity and
      temperature-monitored wet chamber. Each specimen was subjected to two mechanical
      tests in order to measure corneal strain resulting from application of cyclic
      (cyclic regimen) and constant (creep regimen) stress by changing the intra-ocular
      pressure (IOP) within physiological ranges (18-42 mmHg). Corneal shape changes
      were analyzed as a function of IOP and both corneal stress-strain curves and
      creep curves were generated. RESULTS: The procedure was highly accurate and
      repeatable. Upon cyclic stress application, a biomechanical corneal elasticity
      gradient was found in the front-back direction. The average Young's modulus of
      the anterior cornea ranged between 2.28+/-0.87 MPa and 3.30+/-0.90 MPa in
      specimens with and without intact epithelium (P = 0.05) respectively. The Young's
      modulus of the posterior cornea was on average 0.21+/-0.09 MPa and 0.17+/-0.06
      MPa (P>0.05) respectively. The time-dependent strain response of the cornea to
      creep testing was quantified by fitting data to a modified Zener model for
      extracting both the relaxation time and compliance function. CONCLUSION: Cyclic
      and creep mechanical tests are valuable for investigating the strain response of
      the intact human cornea within physiological IOP ranges, providing meaningful
      results that can be translated to clinic. The presence of epithelium influences
      the results of anterior corneal shape changes when monitoring deformation via
      Scheimpflug imaging in inflation experiments of whole eye globes.

PMID- 25397675
TI  - Characterization of arbuscular mycorrhizal fungus communities of Aquilaria
      crassna and Tectona grandis roots and soils in Thailand plantations.
AB  - Aquilaria crassna Pierre ex Lec. and Tectona grandis Linn.f. are sources of resin
      suffused agarwood and teak timber, respectively. This study investigated
      arbuscular mycorrhizal (AM) fungus community structure in roots and rhizosphere
      soils of A. crassna and T. grandis from plantations in Thailand to understand
      whether AM fungal communities present in roots and rhizosphere soils vary with
      host plant species and study sites. Terminal restriction fragment length
      polymorphism complemented with clone libraries revealed that AM fungal community
      composition in A. crassna and T. grandis were similar. A total of 38 distinct
      terminal restriction fragments (TRFs) were found, 31 of which were shared between
      A. crassna and T. grandis. AM fungal communities in T. grandis samples from
      different sites were similar, as were those in A. crassna. The estimated average
      minimum numbers of AM fungal taxa per sample in roots and soils of T. grandis
      were at least 1.89 vs. 2.55, respectively, and those of A. crassna were 2.85 vs.
      2.33 respectively. The TRFs were attributed to Claroideoglomeraceae,
      Diversisporaceae, Gigasporaceae and Glomeraceae. The Glomeraceae were found to be
      common in all study sites. Specific AM taxa in roots and soils of T. grandis and
      A. crassna were not affected by host plant species and sample source (root vs.
      soil) but affected by collecting site. Future inoculum production and utilization
      efforts can be directed toward the identified symbiotic associates of these
      valuable tree species to enhance reforestation efforts. 

PMID- 25397676
TI  - Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced
      activation of NF-kappaB, c-Fos, and nuclear factor of activated T-cells
      cytoplasmic 1 signaling pathway.
AB  - Formononetin (1), a plant-derived phytoestrogen, possesses bone protective
      properties. To address the potential therapeutic efficacy and mechanism of action
      of 1, we investigated its antiosteoclastogenic activity and its effect on nuclear
      factor-kappaB ligand (RANKL)-induced bone-marrow-derived macrophages (BMMs).
      Compound 1 markedly inhibited RANKL-induced osteoclast differentiation in the
      absence of cytotoxicity, by regulating the expression of osteoprotegerin (OPG)
      and RANKL in BMMs and in cocultured osteoblasts. Compound 1 significantly
      inhibited RANKL-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation
      normal T cell expressed and secreted (RANTES), and macrophage inflammatory
      protein-1alpha (MIP-1alpha) in a concentration-dependent manner. These effects
      were accompanied by a decrease in RANKL-induced activation of the NF-kappaB p65
      subunit, degradation of inhibitor kappaBalpha (IkappaBalpha), induction of NF
      kappaB, and phosphorylation of AKT, extracellular-signal regulated kinase (ERK),
      c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38
      MAPK). NF-kappaB siRNA suppressed AKT, ERK, JNK, and p38 MAPK phosphorylation.
      Furthermore, 1 significantly suppressed c-Fos and nuclear factor of activated T
      cells cytoplasmic 1 (NFATc1), key transcription factors during
      osteoclastogenesis. SP600125, a specific inhibitor of JNK, reduced RANKL-induced
      expression of phospho-c-Jun, c-Fos, and NFATc1 and inhibited osteoclast
      formation. These results suggested that 1 acted as an antiresorption agent by
      blocking osteoclast activation. 

PMID- 25397677
TI  - Frequency of and predictive factors for vascular invasion after radiofrequency
      ablation for hepatocellular carcinoma.
AB  - BACKGROUND: Vascular invasion in patients with hepatocellular carcinoma (HCC) is
      representative of advanced disease with an extremely poor prognosis. The detailed
      course of its development has not been fully elucidated. METHODS: We enrolled
      1057 consecutive patients with HCC who had been treated with curative intent by
      radiofrequency ablation (RFA) as an initial therapy from 1999 to 2008 at our
      department. We analyzed the incidence rate of and predictive factors for vascular
      invasion. The survival rate after detection of vascular invasion was also
      analyzed. RESULTS: During a mean follow-up period of 4.5 years, 6075 nodules
      including primary and recurrent lesions were treated by RFA. Vascular invasion
      was observed in 97 patients. The rate of vascular invasion associated with site
      of original RFA procedure was 0.66% on a nodule basis. The incidence rates of
      vascular invasion on a patient basis at 1, 3, and 5 years were 1.1%, 5.9%, and
      10.4%, respectively. Univariate analysis revealed that tumor size, tumor number,
      alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and Lens culinaris
      agglutinin-reactive fraction of alpha-fetoprotein were significant risk
      predictors of vascular invasion. In multivariate analysis, DCP was the most
      significant predictor for vascular invasion (compared with a DCP of <=100 mAu/mL,
      the hazard ratio was 1.95 when DCP was 101-200 mAu/mL and 3.22 when DCP was >200
      mAu/mL). The median survival time after development of vascular invasion was only
      6 months. CONCLUSION: Vascular invasion occurs during the clinical course of
      patients initially treated with curative intent. High-risk patients may be
      identified using tumor markers.

PMID- 25397678
TI  - NK cell activity differs between patients with localized and diffuse cutaneous
      leishmaniasis infected with Leishmania mexicana: a comparative study of TLRs and
      cytokines.
AB  - Leishmania mexicana causes localized (LCL) or diffuse cutaneous leishmaniasis
      (DCL). The cause of dissemination in DCL remains unknown, yet NK cells possibly
      play a role in activating leishmanicidal mechanisms during innate and adaptive
      immune responses. We had previously shown that Leishmania lipophosphoglycan (LPG)
      is a ligand for TLR2, activating human NK cells. We have now analyzed NK cells in
      LCL and DCL patients. NK numbers and effector mechanisms differed drastically
      between both groups of patients: DCL patients showed reduced NK cell numbers;
      diminished IFN-gamma and TNF-alpha production; and lower TLR2, TLR1, and TLR6
      expression as compared to LCL patients. The altered protein expression found in
      NK cells of DCL patients correlated with their down-regulation of IFN-gamma gene
      expression in LPG-stimulated and non-stimulated cells as compared to LCL
      patients. NK cell response was further analyzed according to gender, age, and
      disease evolution in LCL patients showing that female patients produced higher
      IFN-gamma levels throughout the disease progression, whereas TLR2 expression
      diminished in both genders with prolonged disease evolution and age. We
      furthermore show the activation pathway of LPG binding to TLR2 and demonstrated
      that TLR2 forms immunocomplexes with TLR1 and TLR6. In addition to the reduced NK
      cell numbers in peripheral blood, DCL patients also showed reduced NK cell
      numbers in the lesions. They were randomly scattered within the lesions, showing
      diminished cytokine production, which contrasts with those of LCL lesions, where
      NK cells produced IFN-gamma and TNF-alpha and were found within organized
      granulomas. We conclude that in DCL patients the reduced NK-cell numbers and
      their diminished activity, evidenced by low TLR expression and low cytokine
      production, are possibly involved in the severity of the disease. Our results
      provide new information on the contribution of NK cells in Leishmania infections
      of the human host. 

PMID- 25397680
TI  - Clarification requested on potential conflicts of interest in Narayanan et al.

PMID- 25397679
TI  - ARFGAP1 is dynamically associated with lipid droplets in hepatocytes.
AB  - The ARF GTPase Activating Protein 1 (ARFGAP1) associates mainly with the
      cytosolic side of Golgi cisternal membranes where it participates in the
      formation of both COPI and clathrin-coated vesicles. In this study, we show that
      ARFGAP1 associates transiently with lipid droplets upon addition of oleate in
      cultured cells. Also, that addition of cyclic AMP shifts ARFGAP1 from lipid
      droplets to the Golgi apparatus and that overexpression and knockdown of ARFGAP1
      affect lipid droplet formation. Examination of human liver tissue reveals that
      ARFGAP1 is found associated with lipid droplets at steady state in some but not
      all hepatocytes. 

PMID- 25397681
TI  - Scope and mechanism in palladium-catalyzed isomerizations of highly substituted
      allylic, homoallylic, and alkenyl alcohols.
AB  - Herein we report the palladium-catalyzed isomerization of highly substituted
      allylic alcohols and alkenyl alcohols by means of a single catalytic system. The
      operationally simple reaction protocol is applicable to a broad range of
      substrates and displays a wide functional group tolerance, and the products are
      usually isolated in high chemical yield. Experimental and computational
      mechanistic investigations provide complementary and converging evidence for a
      chain-walking process consisting of repeated migratory insertion/beta-H
      elimination sequences. Interestingly, the catalyst does not dissociate from the
      substrate in the isomerization of allylic alcohols, whereas it disengages during
      the isomerization of alkenyl alcohols when additional substituents are present on
      the alkyl chain. 

PMID- 25397682
TI  - Field-induced spin-flop in antiferromagnetic semiconductors with commensurate and
      incommensurate magnetic structures: Li2FeGeS4 (LIGS) and Li2FeSnS4 (LITS).
AB  - Li2FeGeS4 (LIGS) and Li2FeSnS4 (LITS), which are among the first magnetic
      semiconductors with the wurtz-kesterite structure, exhibit antiferromagnetism
      with TN ~ 6 and 4 K, respectively. Both compounds undergo a conventional
      metamagnetic transition that is accompanied by a hysteresis; a reversible spin
      flop transition is dominant. On the basis of constant-wavelength neutron powder
      diffraction data, we propose that LIGS and LITS exhibit collinear magnetic
      structures that are commensurate and incommensurate with propagation vectors km =
      [1/2, 1/2, 1/2] and [0, 0, 0.546(1)], respectively. The two compounds exhibit
      similar magnetic phase diagrams, as the critical fields are temperature
      dependent. The nuclear structures of the bulk powder samples were verified using
      time-of-flight neutron powder diffraction along with synchrotron X-ray powder
      diffraction. (57)Fe and (119)Sn Mossbauer spectroscopy confirmed the presence of
      Fe(2+) and Sn(4+) as well as the number of crystallographically unique positions.
      LIGS and LITS are semiconductors with indirect and direct bandgaps of 1.42 and
      1.86 eV, respectively, according to optical diffuse-reflectance UV-vis-NIR
      spectroscopy.

PMID- 25397683
TI  - Whole blood transcriptional profiling reveals deregulation of oxidative and
      antioxidative defence genes in myelofibrosis and related neoplasms. Potential
      implications of downregulation of Nrf2 for genomic instability and disease
      progression.
AB  - The Philadelphia-negative chronic myeloproliferative neoplasms - essential
      thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) (MPNs) -
      have recently been shown to be associated with chronic inflammation, oxidative
      stress and accumulation of reactive oxygen species (ROS). Using whole blood
      transcriptional profiling, we report that several oxidative stress and anti
      oxidative stress genes are significantly deregulated in MPNs. Among the twenty
      most up- and downregulated genes, ATOX1, DEFB122, GPX8, PRDX2, PRDX6, PTGS1, and
      SEPP1 were progressively upregulated from ET over PV to PMF, whereas AKR1B1,
      CYBA, SIRT2, TTN, and UCP2 were progressively downregulated in ET, PV and PMF
      (all FDR <0.05). The gene Nrf2, encoding the transcription factor nuclear factor
      erythroid 2-related factor 2 (NFE2L2 or Nrf2) was significantly downregulated in
      all MPNs. Nrf2 has a key role in the regulation of the oxidative stress response
      and modulates both migration and retention of hematopoietic stem cells (HSCs) in
      their niche. The patogenetic importance of Nrf2 depletion in the context of
      expansion of the hematopoietic progenitor pool in MPNs is discussed with
      particular focus upon the implications of concomitant downregulation of Nrf2 and
      CXCR4 for stem cell mobilization. 

PMID- 25397685
TI  - Existence and stability of periodic solution of impulsive neural systems with
      complex deviating arguments.
AB  - This paper discusses a class of impulsive neural networks with the variable delay
      and complex deviating arguments. By using Mawhin's continuation theorem of
      coincidence degree and the Halanay-type inequalities, several sufficient
      conditions for impulsive neural networks are established for the existence and
      globally exponential stability of periodic solutions, respectively. Furthermore,
      the obtained results are applied to some typical impulsive neural network systems
      as special cases, with a real-life example to show feasibility of our results. 

PMID- 25397684
TI  - Zinc-finger nuclease knockout of dual-specificity protein phosphatase-5 enhances
      the myogenic response and autoregulation of cerebral blood flow in FHH.1BN rats.
AB  - We recently reported that the myogenic responses of the renal afferent arteriole
      (Af-Art) and middle cerebral artery (MCA) and autoregulation of renal and
      cerebral blood flow (RBF and CBF) were impaired in Fawn Hooded hypertensive (FHH)
      rats and were restored in a FHH.1BN congenic strain in which a small segment of
      chromosome 1 from the Brown Norway (BN) containing 15 genes including dual
      specificity protein phosphatase-5 (Dusp5) were transferred into the FHH genetic
      background. We identified 4 single nucleotide polymorphisms in the Dusp5 gene in
      FHH as compared with BN rats, two of which altered CpG sites and another that
      caused a G155R mutation. To determine whether Dusp5 contributes to the impaired
      myogenic response in FHH rats, we created a Dusp5 knockout (KO) rat in the
      FHH.1BN genetic background using a zinc-finger nuclease that introduced an 11 bp
      frame-shift deletion and a premature stop codon at AA121. The expression of Dusp5
      was decreased and the levels of its substrates, phosphorylated ERK1/2 (p-ERK1/2),
      were enhanced in the KO rats. The diameter of the MCA decreased to a greater
      extent in Dusp5 KO rats than in FHH.1BN and FHH rats when the perfusion pressure
      was increased from 40 to 140 mmHg. CBF increased markedly in FHH rats when MAP
      was increased from 100 to 160 mmHg, and CBF was better autoregulated in the Dusp5
      KO and FHH.1BN rats. The expression of Dusp5 was higher at the mRNA level but not
      at the protein level and the levels of p-ERK1/2 and p-PKC were lower in cerebral
      microvessels and brain tissue isolated from FHH than in FHH.1BN rats. These
      results indicate that Dusp5 modulates myogenic reactivity in the cerebral
      circulation and support the view that a mutation in Dusp5 may enhance Dusp5
      activity and contribute to the impaired myogenic response in FHH rats. 

PMID- 25397686
TI  - Is early oral feeding after gastric cancer surgery feasible? A systematic review
      and meta-analysis of randomized controlled trials.
AB  - AIM: To assess the feasibility and safety of early oral feeding (EOF) after
      gastrectomy for gastric cancer through a systematic review and meta-analysis
      based on randomized controlled trials. METHODS: A literature search in PubMed,
      Embase, Web of Science and Cochrane library databases was performed for eligible
      studies published between January 1995 and March 2014. Systematic review was
      carried out to identify randomized controlled trials comparing EOF and
      traditional postoperative oral feeding after gastric cancer surgery. Meta
      analyses were performed by either a fixed effects model or a random effects model
      according to the heterogeneity using RevMan 5.2 software. RESULTS: Six studies
      remained for final analysis. Included studies were published between 2005 and
      2013 reporting on a total of 454 patients. No significant differences were
      observed for postoperative complication (RR = 0.95; 95%CI, 0.70 to 1.29; P =
      0.75), the tolerability of oral feeding (RR = 0.98; 95%CI, 0.91 to 1.06; P =
      0.61), readmission rate (RR = 1; 95%CI, 0.30 to 3.31; P = 1.00) and incidence of
      anastomotic leakage (RR = 0.31; 95%CI, 0.01 to 7.30; P = 0.47) between two
      groups. EOF after gastrectomy for gastric cancer was associated with significant
      shorter duration of the hospital stay (WMD = -2.36; 95%CI, -3.37 to -1.34;
      P<0.0001) and time to first flatus (WMD = -19.94; 95%CI, -32.03 to -7.84; P =
      0.001). There were no significant differences in postoperative complication,
      tolerability of oral feeding, readmission rates, duration of hospital stay and
      time to first flatus among subgroups stratified by the time to start EOF or by
      partial and total gastrectomy or by laparoscopic and open surgery. CONCLUSIONS:
      The result of this meta-analysis showed that EOF after gastric cancer surgery
      seems feasible and safe, even started at the day of surgery irrespective of the
      extent of the gastric resection and the type of surgery. However, more
      prospective, well-designed multicenter RCTs with more clinical outcomes are
      needed for further validation.

PMID- 25397688
TI  - Plasticized poly(vinyl chloride)-based photonic crystal for ion sensing.
AB  - In this study, we, for the first time, developed a plasticized poly(vinyl
      chloride) (PVC)-based two-dimensional photonic crystal (2D-PhC) optical sensor
      using nanoimprint lithography (NIL), which can perform highly sensitive, fast,
      and selective ion sensing based on ion extraction. Concerning the principle of
      response, present plasticized PVC-based PhC works as a waveguide and a grating.
      Incident light was guided in the bulk of plasticized PVC and, then, guided light
      of a specific wavelength was diffracted by a periodic nanostructure. The guided
      and diffracted light intensity changes of PVC-based PhCs possessing various
      thicknesses were monitored at 580 nm; then, we found that the 0.35 MUm-thick PhC
      film exhibited the highest diffraction intensity. For the ion-sensing
      application, potassium-selective sensing elements involving potassium ionophore
      and lipophilic dye were dissolved in a plasticized PVC-based PhC, and the K(+)
      selective response was successfully observed by monitoring the diffracted peak
      intensity change. The present 2D-PhC optical sensor exhibited a fast response
      within 5 s (95% response time) due to the use of thin film, and sensitivity was
      20 times higher than that of a PVC plane-film optical sensor, due to efficient
      collection of diffracted light by employing a periodic nanostructure of the
      photonic crystal. 

PMID- 25397687
TI  - Searching for synergistic bronchodilators and novel therapeutic regimens for
      chronic lung diseases from a traditional Chinese medicine, Qingfei Xiaoyan Wan.
AB  - Classical Chinese pharmacopeias describe numerous excellent herbal formulations,
      and each prescription is an outstanding pool of effective compounds for drug
      discovery. Clarifying the bioactivity of the combined mechanisms of the
      ingredients in complex traditional Chinese medicine formulas is challenging. A
      classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment
      for prevalent chronic lung disease, was investigated in this work. A mutually
      enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole
      time-of-flight mass spectrometry (UPLC/Q-TOF-MS) characterization system was
      proposed, coupled with a dual-luciferase reporter assay for beta2AR-agonist
      cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B,
      four lignin compounds that showed synergistic bronchodilation effects with
      ephedrine, were revealed. The synergistic mechanism of arctigenin with the
      beta2ARagonist involved with the reduction of free Ca2+ was clarified by a dual
      luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo
      4/AM to monitor changes in the fluorescence. The relaxant and contractile
      responses of airway smooth muscle are regulated by crosstalk between the
      intracellular cAMP and calcium signaling pathways. Our data indicated the non
      selective betaAR agonist ephedrine as the principal bronchodilator of the
      formula, whereas the lignin ingredients served as adjuvant ingredients. A greater
      understanding of the mechanisms governing the control of these pathways, based on
      conventional wisdom, could lead to the identification of novel therapeutic
      targets or new agents for the treatment of asthma and COPD. 

PMID- 25397689
TI  - Occupational exposure to pesticides and resultant health problems among cotton
      farmers of Punjab, Pakistan.
AB  - Occupational exposure to pesticides and resultant health problems were assessed
      among 318 randomly selected cotton farmers from the two districts of Punjab,
      Pakistan. Heavy dependence of farmers on pesticides for pest control was
      reported. A large part (23.3%) of the pesticides belonged to the category highly
      hazardous, whereas the largest part (54.7%) belonged to the category moderately
      hazardous. Some of them (8%) were reported to be used on vegetables. Common
      working practices of high exposure risk were: the confrontation of pesticide
      spills in the stage of spray solution preparation (76.4%), the use of low
      technology and faulty sprayers (67.9%), and spraying under inappropriate weather
      (46.5%). A large proportion (34%) of the farmers reported multiple intoxication
      symptoms by pesticide use; the most common were irritation of skin and eyes,
      headache, and dizziness. Nevertheless, most farmers thought these symptoms were
      usual; only few reported visiting the doctor. Findings clearly indicated a high
      level of risk exposure to pesticides among farmers of the study area, calling
      upon immediate interventions toward increasing awareness about alternative pest
      control practices with less pesticide use.

PMID- 25397692
TI  - Simultaneous tuning porosity and basicity of nickel@nickel-magnesium
      phyllosilicate core-shell catalysts for CO2 reforming of CH4.
AB  - Ni@Ni-Mgphy (Ni-Mgphy = Ni-Mg phyllosilicate) core-shell catalysts were designed
      by hydrothermally treating Ni@SiO2 nanoparticles with magnesium nitrate salt. The
      porosity and basicity of the catalysts were easily tuned by forming Ni-Mgphy
      shell using Ni originating from Ni@SiO2 during the hydrothermal treatment process
      and Mg(NO3)2 as the Ni and Mg sources, respectively. Among Ni@Ni-Mgphy core-shell
      catalysts synthesized under different hydrothermal durations, the catalyst
      treated for 10 h achieved the best catalytic performance for CO2 reforming of CH4
      reaction with stable CO2 and CH4 conversions of around 81% and 78%, respectively,
      within 95 h reaction duration at 700  degrees C. The high Ni accessibility,
      strong basicity, and high structural stability for Ni@Ni-Mgphy core-shell
      catalyst with 10 h treatment time accounted for its superb catalytic performance.
      This method to simultaneously tune the porosity and basicity of Ni@SiO2 core
      shell nanoparticles demonstrates a general way to modify the properties of other
      silica based core-shell nanoparticles through treating them with different metal
      salts. 

PMID- 25397691
TI  - Propranolol associated with endoscopic band ligation reduces recurrence of
      esophageal varices for primary prophylaxis of variceal bleeding: a randomized
      controlled trial.
AB  - OBJECTIVE: The aim of this study was to compare the recurrence of esophageal
      varices (EVs) after endoscopic band ligation (EBL) associated with propranolol
      (PP) versus EBL alone. PATIENTS AND METHODS: Sixty-six cirrhotic outpatients (EBL
      group, n=32 and EBL+PP group, n=34) with high-risk EVs without previous bleeding
      were studied. MAIN OUTCOME MEASUREMENTS: The primary outcome was recurrence of
      EV. The secondary outcomes were EV eradication, bleeding before EV eradication,
      mortality, and adverse events. RESULTS: Demographic characteristics and the
      initial endoscopic findings were similar. EV eradication was achieved in all
      patients. Three patients presented gastrointestinal bleeding before variceal
      eradication, two in the EBL group and one in the EBL+PP group (P=0.13). Six
      patients died (liver failure), two in the EBL group and four in the EBL+PP group
      (P=0.27). Twelve (38%) patients in the EBL group and three (9%) patients in the
      EBL+PP group had variceal recurrence. The risk of recurrence of EVs after
      eradication was significantly higher among patients in the EBL group (P=0.003).
      CONCLUSION: EBL alone and EBL+PP were effective in the primary prophylaxis of
      bleeding from EVs in cirrhotic patients (EV eradication, bleeding before EV
      eradication, mortality, and adverse events were similar in both groups). However,
      variceal recurrence was lower in the EBL+PP group than band ligation alone.

PMID- 25397690
TI  - Structural and compositional changes in the salivary pellicle induced upon
      exposure to SDS and STP.
AB  - Sodium dodecyl sulphate (SDS) and sodium tripolyphosphate (STP) act to remove
      stained pellicle from dentition and loosen deposits on tooth surfaces that may
      become cariogenic over time. This study investigated how SDS and STP impact the
      salivary pellicle adsorbed onto hydroxyapatite and silica sensors using a dual
      polarisation interferometer and a quartz-crystal microbalance with dissipation.
      After the pellicle was exposed to SDS and STP the remaining pellicle, although
      weaker, due to the loss of material, became less dense but with a higher elastic
      component; suggesting that the viscous component of the pellicle was being
      removed. This would imply a structural transformation from a soft but dense
      structured pellicle, to a more diffuse pellicle. In addition, the majority of
      proteins displaced by both SDS and STP were identified as being acidic in nature;
      implying that the negatively charged groups of SDS and STP may be responsible for
      the displacement of the pellicle proteins observed. 

PMID- 25397693
TI  - Release of engineered nanomaterials from polymer nanocomposites: the effect of
      matrix degradation.
AB  - Polymer nanocomposites-polymer-based materials that incorporate filler elements
      possessing at least one dimension in the nanometer range-are increasingly being
      developed for commercial applications ranging from building infrastructure to
      food packaging to biomedical devices and implants. Despite a wide range of
      intended applications, it is also important to understand the potential for
      exposure to these nanofillers, which could be released during routine use or
      abuse of these materials so that it can be determined whether they pose a risk to
      human health or the environment. This article is the second of a pair that review
      what is known about the release of engineered nanomaterials (ENMs) from polymer
      nanocomposites. Two roughly separate ENM release paradigms are considered in this
      series: the release of ENMs via passive diffusion, desorption, and dissolution
      into external liquid media and the release of ENMs assisted by matrix
      degradation. The present article is focused primarily on the second paradigm and
      includes a thorough, critical review of the associated body of peer-reviewed
      literature on ENM release by matrix degradation mechanisms, including
      photodegradation, thermal decomposition, mechanical wear, and hydrolysis. These
      release mechanisms may be especially relevant to nanocomposites that are likely
      to be subjected to weathering, including construction and infrastructural
      materials, sporting equipment, and materials that might potentially end up in
      landfills. This review pays particular attention to studies that shed light on
      specific release mechanisms and synergistic mechanistic relationships. The review
      concludes with a short section on knowledge gaps and future research needs. 

PMID- 25397694
TI  - Nasal reconstruction in panfacial burns: useful techniques in challenging cases.
AB  - Nasal reconstruction after severe panfacial burns can be challenging to correct
      because of scarring, loss of suitable donor sites, and variably limited blood
      supply of local flaps. We describe 2 cases of subtotal nasal reconstruction in
      which we overcame these difficulties. Both cases had alar subunit loss, which had
      left significant functional and esthetic deformities. However, both cases were
      managed very differently because of availability of donor sites.The first patient
      had 70% total body surface area burns with bilateral alar subunit loss: nasal
      reconstruction required a meticulous multistaged forehead flap. The second
      patient required nasal reconstruction using a turn-down flap to maximize take of
      a composite graft from previously burned ear donor sites.A number of surgical
      techniques have been described to manage subtotal burns nasal reconstruction,
      foremost of which are the nasolabial and paramedian forehead flaps. Cartilage
      grafts from the septum and the conchal bowl can be integrated into these flaps.
      Composite grafts can be unpredictable and are often used with caution.Such cases
      demonstrate that large composite grafts can be an extremely robust method of
      reconstruction even in a subset of patients with extensively scarred recipient
      and donor sites. In our second case, composite grafting avoided multistaged
      procedures such as the forehead flap and can be considered as a first-line
      procedure in large alar subunit loss. 

PMID- 25397695
TI  - Treatment of fingertip degloving injury using the bilaterally innervated sensory
      cross-finger flap.
AB  - Treatment of a fingertip degloving injury continues to be a challenge problem.
      This article reports repair of this type of injury using a modified cross-finger
      flap, including both dorsal branches of the digital nerves. From December 2007 to
      March 2010, the flap was used in 17 digits of 17 patients who had a fingertip
      degloving injury. There were 13 men and 4 women with mean age of 33 years. The
      injured fingers requiring reconstruction included 5 index, 6 middle, and 6 ring
      fingers. The mean size of the soft tissue losses was 4.2 * 1.9 cm. The mean flap
      size was 4.4 * 2.2 cm. Neurorrhaphy was performed between the dorsal branches
      harvested with the flap and the digital nerves of the injured finger. For
      comparison, we also collected a series of 28 patients who had a fingertip
      degloving injury treated with a cross-finger flap without nerve repair. In the
      study group, all flaps survived completely. At a mean follow-up of 23 months, the
      average score of static 2-point discrimination on the finger pulp was 7.2 mm.
      According to the visual analog scale, 12 patients had no pain, 4 reported mild
      pain, and 1 experienced moderate pain. Positive Tinel sign was found in only 1
      reconstructed finger. Of the comparison group (mean follow-up, 22 months), the
      average static 2-point discrimination was 9.8 mm. On the basis of the visual
      analog scale, no pain, mild pain, and moderate pain were noted in 18, 7, and 3,
      fingers, respectively. Positive Tinel sign was found in 9 reconstructed fingers.
      The outcomes of the 2 groups were significantly different. The bilaterally
      innervated sensory cross-finger flap is an effective method for repairing the
      fingertip degloving injury. The authors suggest that double nerve repairs should
      be performed to improve the pulp sensation and reduce the incidence of the
      painful neuroma. 

PMID- 25397696
TI  - Secondary subdermal pocket procedure for venous insufficiency after digital
      replantation/revascularization.
AB  - PURPOSE: Venous insufficiency after microsurgical replantation/revascularization
      remained to be a vexing problem for finger failure, despite the level of
      amputation. Other than redo the venous anastomosis, alternative methods such as
      subdermal pocket procedure (SDP) can be used. The aim of this study was to
      incorporate SDP immediately at the time of replantation, when no suitable vein is
      available after digital artery anastomosis; or, as a secondary salvage procedure
      to restore venous drainage for venous insufficiency after initial digital
      replantation/revascularization. MATERIALS AND METHODS: From 1999 to 2010, a total
      of 21 injured digits from 20 patients were collected. The mechanisms of injury
      included 6 guillotine amputations, 1 guillotine near-complete amputation, 12
      crushing amputations, 1 crushing injury, and 1 crushing injury with contact
      thermal burn. The average patients' age was 34.5 years. Subdermal pocket
      procedures were used to all injured digits at different time frame as indicated.
      The patients were divided into 2 groups based on the timing of SDP, either
      primary or secondary. The pocketing period and the time lapse between the initial
      operation and the secondary salvaged SDP were also documented. RESULTS: Group 1
      (13 digits) received primary SDP as means of venous drainage immediately after
      digital artery revascularization. The mean pocketing period was 9.2 days, ranging
      from 7 to 15 days, with a 100% complete survival rate. Group 2 (8 digits)
      received secondary SDP as a salvage procedure when venous congestion became
      apparent later. The mean time lapse between initial operation and salvaged SDP
      was 53.1 hours. The average pocketing period was 7.5 days, with a 75% survival
      rate. CONCLUSIONS: Secondary SDP provides an alternative salvage solution for
      postreplantation venous insufficiency without the need for further microsurgery.

PMID- 25397697
TI  - Koenen tumors in tuberous sclerosis: a review and clinical considerations for
      treatment.
AB  - Koenen tumors, or periungual and subungual fibromas, are a benign, cutaneous
      manifestation of tuberous sclerosis. They are disfiguring, painful, and
      challenging to treat as they frequently recur. Various laser and chemical
      ablation techniques have been described with variable long-term results and there
      is limited published literature to suggest a standard treatment. Through a review
      of the available literature and a successful experience with a patient with lower
      extremity Koenen tumor, we present treatment considerations for managing these
      troublesome tumors. 

PMID- 25397698
TI  - Rbm46 regulates trophectoderm differentiation by stabilizing Cdx2 mRNA in early
      mouse embryos.
AB  - Blastocyst formation represents the first lineage specification by segregation of
      the trophectoderm from the inner cell mass in early embryonic development.
      Transcriptional regulation of Cdx2, which is selectively expressed in and
      essential for the specification of trophectoderm, has been extensively studied.
      However, post-transcriptional regulation of Cdx2 remains largely unknown. In this
      study, we report that RNA-binding protein motif 46 (Rbm46), an RNA-binding motif
      protein with unknown function, directly binds to and stabilizes Cdx2 mRNA in
      early mouse embryos. In addition, knockdown of Rbm46 using RNA interference
      downregulated the majority of trophectoderm markers in mouse embryonic stem cells
      and blocked the allocation of blastomere cells to the trophectoderm in mouse
      embryos. Our study revealed a novel mechanism by which Rbm46 regulates
      trophectoderm specification through stabilizing Cdx2 mRNA in early mouse embryos.

PMID- 25397699
TI  - Questioning the "melting pot": analysis of Alu inserts in three population
      samples from Uruguay.
AB  - The way that immigrants integrate into recipient societies has been discussed for
      decades, mainly from the perspective of the social sciences. Uruguay, as other
      American countries, received diffferent waves of European immigrants, although
      the details of the process of assimilation, when it did occur, are unclear. In
      this study we used genetic markers to understand the process experienced by the
      Basques, one of the major migration waves that populated Uruguay, and their
      relation to other immigrants, as well as to Native American and African
      descendants. For this purpose, we analyzed the allele frequencies of 10 ALU loci
      (A25, ACE, APOA1, B65, D1, F13B, PV92, TPA25, HS2.43, and HS4.65) in three
      samples from Uruguay (two of Basque descendants, one of non-Basque descendants)
      from two locations: Montevideo and Trinidad. No departure from Hardy-Weinberg
      expectations was observed, with the exceptions of the APOA1 and D1 loci in the
      non-Basque descendants' samples. Our data show that the major genetic
      contribution in the three samples comes from Europe (78-88%), with minor African
      (10-15%) and Native American (0-10%) contributions. Genetic distances reveal that
      Basque descendants from Trinidad cluster with Europeans, whereas both Montevideo
      samples cluster together and are separate from other populations, showing two
      diffferent types of integration, related to the general characteristics of each
      regional population. 

PMID- 25397700
TI  - Mitochondrial DNA variability among six South American Amerindian villages from
      the Pano linguistic group.
AB  - Although scattered throughout a large geographic area, the members of the Pano
      linguistic group present strong ethnic, linguistic, and cultural homogeneity, a
      feature that causes them to be considered components of a same "Pano" tribe.
      Nevertheless, the genetic homogeneity between Pano villages has not yet been
      examined. To study the genetic structure of the Pano linguistic group, four major
      Native American mitochondrial DNA (mtDNA) founder haplogroups were analyzed in 77
      Amerindians from six villages of four Pano tribes (Katukina, Kaxinawa, Marubo,
      and Yaminawa) located in the Brazilian Amazon. The central position of these
      tribes in the continent makes them relevant for attempts to reconstruct
      population movements in South America. Except for a single individual that
      presented an African haplogroup L, all remaining individuals presented one of the
      four Native American haplogroups. Significant heterogeneity was observed across
      the six Pano villages. Although Amerindian populations are usually characterized
      by considerable interpopulational diversity, the high heterogeneity level
      observed is unexpected if the strong ethnic, linguistic, and cultural homogeneity
      of the Pano linguistic group is taken into account. The present findings indicate
      that the ethnic, linguistic, and cultural homogeneity does not imply genetic
      homogeneity. Even though the genetic heterogeneity uncovered may be a female
      specific process, the most probable explanation for that is the joint action of
      isolation and genetic drift as major factors influencing the genetic structure of
      the Pano linguistic group. 

PMID- 25397701
TI  - Phylogeography of E1b1b1b-M81 haplogroup and analysis of its subclades in
      Morocco.
AB  - In this study we analyzed 295 unrelated Berber-speaking men from northern,
      central, and southern Morocco to characterize frequency of the E1b1b1b-M81
      haplogroup and to refine the phylogeny of its subclades: E1b1b1b1-M107, E1b1b1b2
      M183, and E1b1b1b2a-M165. For this purpose, we typed four biallelic
      polymorphisms: M81, M107, M183, and M165. A large majority of the Berber-speaking
      male lineages belonged to the Y-chromosomal E1b1b1b-M81 haplogroup. The frequency
      ranged from 79.1% to 98.5% in all localities sampled. E1b1b1b2-M183 was the most
      dominant subclade in our samples, ranging from 65.1% to 83.1%. In contrast, the
      E1b1b1b1-M107 and E1b1b1b2a-M165 subclades were not found in our samples. Our
      results suggest a predominance of the E1b1b1b-M81 haplogroup among Moroccan
      Berber-speaking males with a decreasing gradient from south to north. The most
      prevalent subclade in this haplogroup was E1b1b1b2-M183, for which diffferences
      among these three groups were statistically significant between central and
      southern groups. 

PMID- 25397702
TI  - Human paternal lineages, languages, and environment in the Caucasus.
AB  - Publications that describe the composition of the human Y-DNA haplogroup in
      diffferent ethnic or linguistic groups and geographic regions provide no explicit
      explanation of the distribution of human paternal lineages in relation to
      specific ecological conditions. Our research attempts to address this topic for
      the Caucasus, a geographic region that encompasses a relatively small area but
      harbors high linguistic, ethnic, and Y-DNA haplogroup diversity. We genotyped 224
      men that identified themselves as ethnic Georgian for 23 Y-chromosome short
      tandem-repeat markers and assigned them to their geographic places of origin. The
      genotyped data were supplemented with published data on haplogroup composition
      and location of other ethnic groups of the Caucasus. We used multivariate
      statistical methods to see if linguistics, climate, and landscape accounted for
      geographical diffferences in frequencies of the Y-DNA haplogroups G2, R1a, R1b,
      J1, and J2. The analysis showed significant associations of (1) G2 with
      wellforested mountains, (2) J2 with warm areas or poorly forested mountains, and
      (3) J1 with poorly forested mountains. R1b showed no association with
      environment. Haplogroups J1 and R1a were significantly associated with
      Daghestanian and Kipchak speakers, respectively, but the other haplogroups showed
      no such simple associations with languages. Climate and landscape in the context
      of competition over productive areas among diffferent paternal lineages, arriving
      in the Caucasus in diffferent times, have played an important role in shaping the
      present-day spatial distribution of patrilineages in the Caucasus. This spatial
      pattern had formed before linguistic subdivisions were finally shaped, probably
      in the Neolithic to Bronze Age. Later historical turmoil had little influence on
      the patrilineage composition and spatial distribution. Based on our results, the
      scenario of postglacial expansions of humans and their languages to the Caucasus
      from the Middle East, western Eurasia, and the East European Plain is plausible. 

PMID- 25397703
TI  - Human diversity in Jordan: polymorphic Alu insertions in general Jordanian and
      Bedouin groups.
AB  - Jordan, located in the Levant region, is an area crucial for the investigation of
      human migration between Africa and Eurasia. However, the genetic history of
      Jordanians has yet to be clarified, including the origin of the Bedouins today
      resident in Jordan. Here, we provide new genetic data on autosomal independent
      markers in two Jordanian population samples (Bedouins and the general population)
      to begin to examine the genetic diversity inside this country and to provide new
      information about the genetic position of these populations in the context of the
      Mediterranean and Middle East area. The markers analyzed were 18 Alu polymorphic
      insertions characterized by their identity by descent, known ancestral state
      (lack of insertion), and apparent selective neutrality. The results indicate
      significant genetic diffferences between Bedouins and general Jordanians (p =
      0.038). Whereas Bedouins show a close genetic proximity to North Africans,
      general Jordanians appear genetically more similar to other Middle East
      populations. In general, these data are consistent with the hypothesis that
      Bedouins had an important role in the peopling of Jordan and constitute the
      original substrate of the current population. However, migration into Jordan in
      recent years likely has contributed to the diversity among current Jordanian
      population groups. 

PMID- 25397704
TI  - Reconstruction of the orbit.

PMID- 25397705
TI  - The orbits--anatomical features in view of innovative surgical methods.
AB  - The aim of this article is to update on anatomical key elements of the orbits in
      reference to surgical innovations. This is a selective literature review
      supplemented with the personal experience of the authors, using illustrations and
      photographs of anatomical dissections. The seven osseous components of the orbit
      can be conceptualized into a simple geometrical layout of a four-sided pyramid
      with the anterior aditus as a base and the posterior cone as apex. All
      neurovascular structures pass through bony openings in the sphenoid bone before
      diversification in the mid and anterior orbit. A set of landmarks such as the
      optic and maxillary strut comes into new focus. Within the topographical surfaces
      of the internal orbit the lazy S-shaped floor and the posteromedial bulge are
      principal determinants for the ocular globe position. The inferomedial orbital
      strut represents a discernible sagittal buttress. The periorbita and orbital soft
      tissue contents--extraocular muscles, septae, neurovasculature--are detailed and
      put into context with periorbital dissection.

PMID- 25397706
TI  - Orbital fractures: pathophysiology and implant materials for orbital
      reconstruction.
AB  - Among midfacial fractures, the frequency of orbital injuries is surpassed only by
      nasal fractures. A clear understanding of orbital anatomy and the pathophysiology
      of these injuries is critical to accurate diagnosis, precise surgical
      reconstruction, and successful clinical outcomes. This chapter reviews the
      mechanism of injury and pathophysiology of orbital fractures as well as the
      implant materials that are currently used for surgical reconstruction. 

PMID- 25397707
TI  - Diagnosis and treatment of optic nerve trauma.
AB  - Decreasing visual acuity secondary to orbital trauma or orbital and anterior
      skull base surgery may be caused by either sudden space-occupying intraorbital
      lesions, including retrobulbar hemorrhage (RBH), or direct damage to the
      prechiasmatic pathway. Contrary to traumatic optic neuropathy, RBH must be
      diagnosed and treated immediately to prevent permanent damage to the visual
      system. Therefore, monitoring and handling of visual pathway damage are
      mandatory. Flash visual evoked potentials and electroretinograms can provide
      evidence of the status of conductivity of the visual pathway when clinical
      assessment is not feasible. Both are thus essential diagnostic procedures not
      only for primary diagnosis but also for intraoperative evaluation. In case of RBH
      surgical decompression is compulsory. However, traumatic optic neuropathy does
      not respond to either corticosteroids or optic canal surgery. Modern
      craniomaxillofacial surgery requires detailed consideration of the diagnosis and
      treatment of traumatic visual pathway damage with the ultimate goal of preserving
      visual acuity. 

PMID- 25397708
TI  - Imaging of the midfacial and orbital trauma.
AB  - The severity of midfacial and orbital injuries depends on the one hand on cause,
      force vector, load point, or area and on the other hand on the bony and soft
      tissue resistance as well as individual anatomy. These variables result in a
      variety of possible injuries of the midfacial and orbital complex. The time
      critical choice of an adequate imaging modality of these injuries is influenced
      by the possible severity of concomitant injuries. Besides the confirmation of a
      clinical diagnosis, the need for high-resolution three-dimensional imaging for
      preoperative planning of facial reconstruction using intraoperative navigation
      has become more and more important in the past years. To achieve optimal
      functional and esthetic outcomes, the anatomical complexity of the midface has to
      be addressed and the adequate imaging modality has to be chosen keeping the
      upcoming surgical treatment in mind. The current imaging modalities for midfacial
      and orbital trauma are presented and critically evaluated depending on the
      indications. Furthermore, new strategies to support surgeons in achieving best
      possible midfacial reconstructions are discussed. An algorithm to choose the
      adequate imaging modality in midfacial and orbital traumatology is provided. 

PMID- 25397709
TI  - Surgical approaches to the orbit in primary and secondary reconstruction.
AB  - The key to orbital surgery is exposure of the bony orbit. This article presents,
      in a stepwise fashion, the subtarsal and transconjunctival approaches to the
      orbital floor and medial wall. 

PMID- 25397710
TI  - Intraoperative imaging in orbital and midface reconstruction.
AB  - The orbit is very often affected by injuries which can leave patients not only
      with esthetic deficits, but also with functional impairments if reconstruction is
      inadequate. Computer-assisted surgery helps to achieve predictable outcomes in
      reconstruction. Today, intraoperative three-dimensional (3D) imaging is an
      important element in the workflow of computer-assisted orbital surgery. Clinical
      and radiological diagnosis by means of computed tomography is followed by
      preoperative computer-assisted planning to define and simulate the desired
      outcome of reconstruction. In difficult cases, intraoperative navigation helps in
      the implementation of procedure plans at the site of surgery. Intraoperative 3D
      imaging then allows an intraoperative final control to be made and the outcome of
      the surgery to be validated. Today, this is preferably done using 3D C-arm
      devices based on cone beam computed tomography. They help to avoid malpositioning
      of bone fragments and/or inserted implants assuring the quality of complex
      operations and reducing the number of secondary interventions necessary. 

PMID- 25397711
TI  - Orbital reconstruction: prefabricated implants, data transfer, and revision
      surgery.
AB  - External impact to the orbit may cause a blowout or zygomatico-maxillary
      fractures. Diagnosis and treatment of orbital wall fractures are based on both
      physical examination and computed tomography scan of the orbit. Injuries of the
      orbit often require a reconstruction of its orbital walls. Using computer
      assisted techniques, anatomically preformed orbital implants, and intraoperative
      imaging offers precise and predictable results of orbital reconstructions.
      Secondary reconstruction of the orbital cavity is challenging due to fractures
      healed in malposition, defects, scarring, and lack of anatomic landmarks, and
      should be avoided by precise primary reconstruction. The development of preformed
      orbital implants based on topographical analysis of the orbital cavity was a
      milestone for the improvement of primary orbital reconstruction. 

PMID- 25397712
TI  - Reconstruction of periorbital soft tissue defects.
AB  - Because of the complex anatomy and fine mechanics of the periorbital soft
      tissues, the reconstruction of this region can be particularly daunting. Through
      a structured assessment of the defect, based on subunit analysis and thorough
      understanding of the surgical layers, we believe to allow the reconstructive
      surgeon to develop an algorithmic approach to these complex problems. The sequela
      of a suboptimal reconstruction do not only result in an inferior aesthetic
      result, but also have the potential for long-term functional problems such as
      epiphora, dry eye, ptosis, eyelid retraction, and thus requiring secondary
      surgery. There is no better time to aim for a perfect reconstruction than at the
      time of the initial surgery. In this chapter, we hope to encourage the reader to
      strengthen and recapitulate these analytical skills and present the most commonly
      used and studied techniques to help achieve a reproducible functional and
      aesthetically appealing result. 

PMID- 25397713
TI  - Orbital tumors: operative and therapeutic strategies.
AB  - The term "orbital tumors" includes diverse benign or malignant space-occupying
      lesions of the orbit, often leading to dystopia of the eyeball, motility
      disturbances, diplopia, visual field defects, and sometimes a complete loss of
      vision. Removing these tumors in a limited surgical field is challenging.
      Therefore, the preservation of function is a primary concern. We retrospectively
      reviewed 671 patients with orbital tumors from October 1999 to June 2014.
      Diagnosis on referral, presenting symptoms, radiological records, histology of
      the primary tumor or orbital metastasis, and treatment choice were analyzed.
      Among the 671 orbital tumors, 40% were accessed anteriorly, 36% via an orbitotomy
      with temporary osteotomy, and 23.9% underwent an orbital exenteration. As an
      illustration of the operative strategies with subsequent reconstructions, a
      distinction was made among the main indication groups: (1) function-preserving
      therapy for retrobulbar tumors, (2) malignant tumors of the conjunctiva and the
      eyelids, (3) exenteration of the orbit and subsequent reconstruction, and (4)
      operative and therapeutic strategy for orbital metastases. Adequate preoperative
      use of modern imaging techniques and thorough planning of the operation are
      crucial. Accurate histopathological diagnosis is crucial for planning appropriate
      therapeutic and surgical interventions. New innovative treatment concepts and
      surgical techniques arise from the close cooperation of related disciplines such
      as ophthalmology and neurosurgery. Although an orbital exenteration in patients
      with eyelid and conjunctival carcinomas can now often be avoided, eye-preserving
      treatment for locally advanced carcinomas of the conjunctiva and eyelid must be
      attempted. For extensive orbital malignancies, orbital exenteration is curative.
      In this context, primary closure of the orbit can improve the patient's quality
      of life and avoid subsequent complications. Concerning orbital metastasis, early
      diagnosis can preserve function and fulfil the esthetic demands of the patients.
      In palliative tumor disease, operative procedures such as orbital decompression
      or tumor debulking can reduce patient complaints and contribute to improved
      quality of life. 

PMID- 25397714
TI  - Chimeric flaps and "their variations": different options for immediate
      reconstruction of massive facial defects.
AB  - The reconstruction of massive head and neck defects is a difficult challenge,
      requiring restoration of bone, skin, and oral lining. Their complex three
      dimensional nature often dictates the need of more than a single osteocutaneous
      flap for intra- and extra-oral reconstruction.Conventional reconstructive options
      can be considered, but there is no single ideal osteocutaneous free or pedicled
      flap providing an unlimited length of bone and skin paddle, or that could orient
      the skin paddle independently of the vascularized bone. The surgeon should then
      be aware of more complex options for reconstruction of extensive three
      dimensional defects, namely chimeric free flaps and "their variations." They can
      be stratified in three types, either based on their intrinsic vasculature
      perforated-based, branch-based, or whether they are prefabricated (surgical
      junction by microanastomosis).Despite morbidity and not perfect matching in terms
      of skin texture and pliability, these techniques are a good alternative in the
      presence of partial defects, especially in the context of immediate oncological
      reconstruction, where facial transplantation is not considered. 

PMID- 25397715
TI  - Use of copolymer polylactic and polyglycolic acid resorbable plates in repair of
      orbital floor fractures.
AB  - The fractures of the orbital floor are common after craniofacial trauma. Repair
      with resorbable plates is a viable reconstructive option; however, there are few
      reports in the literature. This study describes our experience using copolymer
      polylactic and polyglycolic acid (PLLA/PGA) orbital reconstruction plates
      (LactoSorb, Lorenz Surgical, Jacksonville, FL) in 29 cases of the orbital floor
      fracture repair. We conducted a retrospective review of 29 orbital floor
      fractures at a single institution repaired through transconjunctival, preseptal
      dissection using PLLA/PGA plates fashioned to repair the orbital floor defect.
      Associated fractures included zygomaticomaxillary, LeFort, and nasoethmoid
      fractures. There were six patients with complications. Four patients had
      transient diplopia with complete resolution of symptoms within 1 year. One
      patient had diplopia postoperatively, but was later lost to follow-up. Two
      patients have had persistent enophthalmos since 1 year. In each of these cases,
      the floor fracture was coincident with significant panfacial or neurotrauma. We
      did not encounter any adverse inflammatory reactions to the implant material
      itself. The study concluded that orbital floor fracture repair with resorbable
      plates is safe, relatively easy to perform, and in the majority of cases was
      effective without complications. In the presence of severe orbital trauma, more
      rigid implant materials may be appropriate. 

PMID- 25397716
TI  - Morphometric analysis of the upper lip in Koreans.
AB  - The aims of this study were to provide the various dimensions of the philtrum and
      upper red lip in Korean young adults and to identify morphological
      characteristics of these structures in Koreans. A total of 10 dimensions of the
      philtrum and upper red lip were measured in 251 healthy young adults. Various
      indices were calculated among the measured features. The philtrum could be
      classified into three types according to its shape and index data. The mean
      height of the philtrum was 15.6 mm and the mean width of the mouth was 45.5 mm.
      The width of the superior and inferior philtrum, the height of philtrum, the
      width of the mouth, and the height of the upper red lip were significantly larger
      in males than in females (p < 0.05). A subtle morphological difference in Cupid
      bow was observed between the genders. There was a negative correlation between
      the length of the philtral column and the height of the upper red lip (p < 0.05).
      Furthermore, differences were identified in the dimensions of the philtrum and
      the upper red lip between Koreans and Caucasians. The results of this study could
      be a useful morphological basis for correction and reconstruction of the upper
      lip. 

PMID- 25397717
TI  - Quality of life in patients who underwent rhinoplasty.
AB  - Despite developments in the therapeutic field of cosmetic surgery, there is a
      little information about the effects of cosmetic procedures on quality of life
      (QOL), especially in Iran. Rhinoplasty is the most common cosmetic surgeries. The
      aim of this study was to evaluate QOL and General Health before and after
      rhinoplasty. Patients aged 18 to 55 years seeking cosmetic rhinoplasty were
      included in this study. Demographic information such as age, sex, marital status,
      and education of patients were recorded. General Health Questionnaire (GHQ-28)
      and World Health Organization Quality of Life (WHOQOL-BREF) questionnaire were
      completed by a single investigator for all patients, before and 3 months after
      rhinoplasty. A total of 50 patients were enrolled in this study. Overall, 78%
      were women and 22% were men. QOL did not change significantly (p < 0.05) except
      for its psychological domain, which did not depend on sex, age, marital, and
      educational status. Also, general health changes after rhinoplasty was not
      statistically significant (p > 0.05) and it did not depend on age, sex, and
      marital status. It seems that cosmetic rhinoplasty has no significant effect on
      general health and QOL except for its psychological health domain. 

PMID- 25397718
TI  - Proteomic study reveals a co-occurrence of gallic acid-induced apoptosis and
      glycolysis in B16F10 melanoma cells.
AB  - Gallic acid (GA) has long been associated with a wide range of biological
      activities. In this study, its antitumor effect against B16F10 melanoma cells was
      demonstrated by MTT assay, cell migration assay, wound-healing assay, and flow
      cytometric analysis. GA with a concentration >200 MUM shows apoptotic activity
      toward B16F10 cells. According to Western blotting data, overexpressions of
      cleaved forms of caspase-9, caspase-3, and PARP-1 and pro-apoptotic Bax and Bad,
      accompanied by underexpressed anti-apoptotic Bcl-2 and Bcl-xL indicate that GA
      induces B16F10 cell apoptosis via mitochondrial pathway. The 2-DE based
      comparative proteomics was further employed in B16F10 cells with and without GA
      treatment for a large-scale protein expression profiling. A total of 41
      differential protein spots were quantified, and their identities were
      characterized using LC-MS/MS analysis and database matching. In addition to some
      regulated proteins that were associated with apoptosis, interestingly, some
      identified proteins involved in glycolysis such as glucokinase, alpha-enolase,
      aldolase, pyruvate kinase, and GAPDH were simultaneously up-regulated, which
      reveals that the GA-induced cellular apoptosis in B16 melanoma cells is
      associated with metabolic glycolysis. 

PMID- 25397719
TI  - Intermolecular and Intramolecular Electron Transfer Processes from Excited
      Naphthalene Diimide Radical Anions.
AB  - Excited radical ions are interesting reactive intermediates owing to powerful
      redox reactivities, which are applicable to various reactions. Although their
      reactivities have been examined for many years, their dynamics are not well
      defined. In this study, we examined intermolecular and intramolecular electron
      transfer (ET) processes from excited radical anions of naphthalene-1,4,5,8
      tetracarboxydiimide (NDI(*-)*). Intermolecular ET processes between NDI(*-)* and
      various electron acceptors were confirmed by transient absorption measurements
      during laser flash photolysis of NDI(*-) generated by pulse radiolysis. Although
      three different imide compounds were employed as acceptors for NDI(*-)*, the
      bimolecular ET rate constants were similar in each acceptor, indicating that ET
      is not the rate-determining step. Intramolecular ET processes were examined by
      applying femtosecond laser flash photolysis to two series of dyad compounds,
      where NDI was selectively reduced chemically. The distance dependence of the ET
      rate constants was described by a beta value of 0.3 A(-1), which is similar or
      slightly smaller than the reported values for donor-acceptor dyads with phenylene
      spacers. Furthermore, by applying the Marcus theory to the driving force
      dependence of the ET rate constants, the electronic coupling for the present ET
      processes was determined. 

PMID- 25397720
TI  - Formation of difluorosulfane complexes of the third row transition metals by
      sulfur-to-metal fluorine migration in trifluorosulfane metal complexes: the
      anomaly of trifluorosulfane iridium tricarbonyl.
AB  - The stability of the experimentally known complex (Et3P)2Ir(CO)(Cl)(F)(SF3) of
      the third row transition metal iridium suggests that SF3 complexes of the third
      row transition metals might be viable species in contrast to the SF3 complexes of
      the first row transition metals previously studied by theoretical methods.
      However, the metal complexes [M](SF3) ([M] = Ta(CO)5, Re(CO)4, CpW(CO)2,
      CpOs(CO), and CpPt) containing three-electron donor tetrahedral SF3 ligands are
      thermodynamically disfavored relative to the isomeric [M](SF2)(F) derivatives
      with predicted energy differences ranging from -19 to -44 kcal/mol. The one
      exception is an Ir(SF3)(CO)3 isomer containing a one-electron donor pseudo-square
      pyramidal SF3 ligand having essentially the same energy as the lowest energy
      Ir(SF2)(F)(CO)3 isomer. This, as well as the stability of the known
      (Et3P)2Ir(CO)(Cl)(F)(SF3), suggests that metal complexes containing one-electron
      donor pseudo-square-pyramidal SF3 ligands might be viable synthetic objectives in
      contrast to those containing three-electron donor tetrahedral SF3 ligands. The
      [M](SF2)(F) derivatives formed by sulfur-to-metal fluorine migration from
      isomeric [M](SF3) complexes are predicted to be viable toward SF2 dissociation to
      give the corresponding [M](F) derivatives. This suggests the possibility of
      synthesizing metal complexes of the difluorosulfane (SF2) ligand via the
      corresponding metal trifluorosulfane complexes with the SF3(+) cation as the
      ultimate source of the SF2 ligand. Such a synthetic approach bypasses the need
      for the very unstable SF2 as a synthetic reagent. 

PMID- 25397721
TI  - Comparing multilabel classification methods for provisional biopharmaceutics
      class prediction.
AB  - The biopharmaceutical classification system (BCS) is now well established and
      utilized for the development and biowaivers of immediate oral dosage forms. The
      prediction of BCS class can be carried out using multilabel classification.
      Unlike single label classification, multilabel classification methods predict
      more than one class label at the same time. This paper compares two multilabel
      methods, binary relevance and classifier chain, for provisional BCS class
      prediction. Large data sets of permeability and solubility of drug and drug-like
      compounds were obtained from the literature and were used to build models using
      decision trees. The separate permeability and solubility models were validated,
      and a BCS validation set of 127 compounds where both permeability and solubility
      were known was used to compare the two aforementioned multilabel classification
      methods for provisional BCS class prediction. Overall, the results indicate that
      the classifier chain method, which takes into account label interactions,
      performed better compared to the binary relevance method. This work offers a
      comparison of multilabel methods and shows the potential of the classifier chain
      multilabel method for improved biological property predictions for use in drug
      discovery and development. 

PMID- 25397722
TI  - Nurses' use of clinical decision support: a literature review.
AB  - Little is known regarding nurses' usage of clinical decision support systems. A
      review of the literature was conducted to understand the extant knowledge
      surrounding the topic of nurses' usage of clinical decision support systems. The
      common themes that emerged from the review of literature on clinical decision
      support systems usage by nurses include (1) nurse factors affecting usage, (2)
      patient factors affecting usage, (3) technology and design factors affecting
      usage, and (4) organizational factors affecting usage. Two major implications are
      that these systems may not be designed to support nursing practice and may not be
      having the intended effect on patient care and quality. 

PMID- 25397723
TI  - Use of a mobile device by nursing home residents for long-term care comprehensive
      geriatric self-assessment: a feasibility study.
AB  - Long-term-care comprehensive geriatric assessments, such as the Minimum Data Set
      3.0, are used to evaluate the clinical, psychological, and personal status of
      residents in long-term-care nursing facilities. Nursing staff conducts assessment
      interviews, thereby increasing the workload of nurses and the cost of patient
      care. This study explored the ability of nursing home residents to use two
      different mobile devices for a geriatric self-assessment. Study participants were
      residents of long-term-care nursing homes. A modified Minimum Data Set 3.0 was
      converted to a format for use with a 6-inch mobile pad and a 3.7-inch mobile
      smartphone. The survey completion rate and the response time were measured. A
      Technology Assessment Model questionnaire analyzed the participants' experience.
      All participants were able to use a 6-inch pad, with an average completion rate
      of 92.9% and an average time for completion of 21 minutes. Only 20% of the
      participants could complete the assessment with the 3.7-inch smartphone. The
      participants found the 6-inch pad easier to use than the 3.7-inch smartphone.
      This exploratory study suggests that nursing home residents are able to use a
      mobile device to perform a geriatric self-assessment and delineates the
      importance of the ergonomics of the device. 

PMID- 25397724
TI  - Impact of an electronic medication administration record on medication
      administration efficiency and errors.
AB  - The study aims were to evaluate the impact of electronic medication
      administration record implementation on medication administration efficiency and
      occurrence of medication errors as well as to identify the predictors of
      medication administration efficiency in an acute care setting. A prospective,
      observational study utilizing time-and-motion technique was conducted before and
      after electronic medication administration record implementation in November
      2011. A total of 156 cases of medication administration activities (78 pre- and
      78 post-electronic medication administration record) involving 38 nurses were
      observed at the point of care. A separate retrospective review of the hospital
      Midas+ medication error database was also performed to collect the rates and
      origin of medication errors for 6 months before and after electronic medication
      administration record implementation. The mean medication administration time
      actually increased from 11.3 to 14.4 minutes post-electronic medication
      administration record (P = .039). In a multivariate analysis, electronic
      medication administration record was not a predictor of medication administration
      time, but the distractions/interruptions during medication administration process
      were significant predictors. The mean hospital-wide medication errors
      significantly decreased from 11.0 to 5.3 events per month post-electronic
      medication administration record (P = .034). Although no improvement in
      medication administration efficiency was observed, electronic medication
      administration record improved the quality of care with a significant decrease in
      medication errors. 

PMID- 25397725
TI  - What's new in Shock, December 2014?

PMID- 25397729
TI  - Structural evolution and membrane interaction of the 40-residue beta amyloid
      peptides: differences in the initial proximity between peptides and the membrane
      bilayer studied by solid-state nuclear magnetic resonance spectroscopy.
AB  - Interactions between the beta amyloid (Abeta) peptides and cellular membranes
      have severe consequences such as neuronal cell disruption and therefore may play
      important roles in Alzheimer's disease. Understanding the structural basis behind
      such interactions, however, is hindered by the complexity of the Abeta-membrane
      systems. In particular, because the Abeta peptides are partially incorporated in
      the membrane bilayer after enzymatic cleavage, there are multiple possibilities
      in terms of the initial proximity between the peptides and membranes. Structural
      studies using in vitro model systems with either externally added or
      preincorporated Abeta in membrane bilayers resulted in distinct evolution
      pathways. Previous work has shown that the externally added Abeta formed long and
      mature filaments, while preincorporated Abeta generated short and curvy fibrils.
      In this study, we perform detailed characterizations on the structural evolution
      and membrane interaction for these two pathways, using a combination of solid
      state nuclear magnetic resonance spectroscopy and other techniques. For the
      externally added Abeta, we determined the residue-specific structural evolution
      during the fibrillation process. While the entire fibrillation process for the
      externally added Abeta was slow, the preincorporated Abeta generated Abeta-lipid
      complexes rapidly. Specific interactions between the lipids and peptides were
      observed, suggesting the colocalization of lipids and peptides within the
      complex. Formation of such a complex induced molecular-level changes in the lipid
      bilayer, which may serve as a possible mechanism of membrane disruption. 

PMID- 25397730
TI  - Hygroscopic influence on the semisolid-to-liquid transition of secondary organic
      materials.
AB  - The effect of relative humidity (RH) on the rebound of particles composed of
      isoprene, alpha-pinene, and toluene secondary organic materials (SOMs) was
      studied. A three-arm impaction apparatus was used to study rebound from 5 to 95%
      RH at 298 K. Calibration experiments using sucrose particles of variable but
      known viscosities showed that the transition from rebounding to adhering
      particles occurred for a change in viscosity from 100 to 1 Pa s, corresponding to
      a transition from semisolid to liquid material. The experimentally determined
      rebound fractions of the studied SOMs were compared with results from a model of
      the rebound processes of hard particles, taking into account the particle kinetic
      energy, van der Waals forces, and RH-dependent capillary forces. For low RH
      values, the hard-particle model explained the diameter-dependent rebound behavior
      for all studied SOMs. For elevated RH, however, the experimental observations
      deviated from the model predictions. On the basis of the calibration experiments
      using sucrose particles as well as a comparison between the observations and the
      predictions of the hard-particle model, the interpretation is made that a
      semisolid-to-liquid transition occurred at elevated RH. Material softening,
      increased adhesion, or a combination of the two implied the action of additional
      modes of energy relaxation that were not included in the hard-particle model. The
      RH threshold for the semisolid-to-liquid phase transition was 40% RH for isoprene
      SOM, 70% for toluene SOM, and 70% for alpha-pinene SOM. A correlation between the
      rebound fraction and the hygroscopic growth factor G was demonstrated, implying
      that absorbed water volume was a dominant governing factor of the semisolid-to
      liquid transition for the studied classes of SOM. Simple heuristic rules based on
      G of 1.15 for the semisolid-to-liquid phase transition could be used for
      prognostication of the SOM phase in modeling applications at 298 K. With respect
      to atmospheric processes, the findings of this study suggest that both the
      chemical composition and the RH influence the phase state of organic particles.
      The findings can explain reports of solid organic particles for terpene-dominant
      conditions of a boreal forest at low RH compared to reports of liquid organic
      particles for isoprene-dominant tropical forests at high RH. 

PMID- 25397731
TI  - n-BuLi as a highly efficient precatalyst for hydrophosphonylation of aldehydes
      and unactivated ketones.
AB  - It was found for the first time that organic alkali metal compounds serve as
      highly efficient precatalysts for the hydrophosphonylation reactions of aldehydes
      and unactivated ketones with dialkyl phosphite under mild conditions. For ketone
      substrates, a reversible reaction was observed, and the influence of catalyst
      loading and reaction temperature on the reaction equilibrium was studied in
      detail. Overall, the hydrophosphonylation reactions catalyzed by 0.1 mol % n-BuLi
      were completed within 5 min for a broad range of substrates and generated a
      series of alpha-hydroxy phosphonates in high yields. 

PMID- 25397732
TI  - Atomistic features in the electrochemical potential drop across a graphene grain
      boundary.
AB  - A recent publication presents a new computational approach to the local
      electrochemical potential in the vicinity of a graphene grain boundary subject to
      an in-plane electric current [1]. The local electrochemical potential can be
      measured using scanning tunneling potentiometry, a method related to scanning
      tunneling microscopy. The paper predicts that atomistic features should be
      measurable. These features reflect the local electrochemical potential drop
      caused by the opaque grain boundary which is non-transparent to ballistic
      electrons. The paper has implications not only for scanning tunneling
      potentiometry, but also for Kelvin probe-force microscopy which can also measure
      the local electrochemical potential. In addition it could help to understand
      electronic transport across metallic nanocontacts. 

PMID- 25397733
TI  - Data-driven techniques for detecting dynamical state changes in noisily measured
      3D single-molecule trajectories.
AB  - Optical microscopes and nanoscale probes (AFM, optical tweezers, etc.) afford
      researchers tools capable of quantitatively exploring how molecules interact with
      one another in live cells. The analysis of in vivo single-molecule experimental
      data faces numerous challenges due to the complex, crowded, and time changing
      environments associated with live cells. Fluctuations and spatially varying
      systematic forces experienced by molecules change over time; these changes are
      obscured by "measurement noise" introduced by the experimental probe monitoring
      the system. In this article, we demonstrate how the Hierarchical Dirichlet
      Process Switching Linear Dynamical System (HDP-SLDS) of Fox et al. [IEEE
      Transactions on Signal Processing 59] can be used to detect both subtle and
      abrupt state changes in time series containing "thermal" and "measurement" noise.
      The approach accounts for temporal dependencies induced by random and "systematic
      overdamped" forces. The technique does not require one to subjectively select the
      number of "hidden states" underlying a trajectory in an a priori fashion. The
      number of hidden states is simultaneously inferred along with change points and
      parameters characterizing molecular motion in a data-driven fashion. We use large
      scale simulations to study and compare the new approach to state-of-the-art
      Hidden Markov Modeling techniques. Simulations mimicking single particle tracking
      (SPT) experiments are the focus of this study. 

PMID- 25397734
TI  - Thermal reactivity of neutral and oxidized ferrocenyl-substituted enediynes.
AB  - The coupling of two equivalents of ethynylferrocene (2) with one equivalent of
      1,2-diiodocyclohexene (1) and 1,2-diiodobenzene (4) using Sonogashira cross
      coupling conditions led to 1,2-bis(ferrocenylethynyl)cyclohexene (3) and 1,2
      bis(ferrocenylethy-nyl)benzene (5), respectively. At high temperatures enediynes
      3 and 5 showed exothermic signals in differential scanning calorimetry (DSC)
      measurements, suggestive of intramolecular diradicaloid ring formation (Bergman
      (C1-C6) or Schreiner-Pascal (C1-C5) cyclizations). The oxidation of 3 and 5 to
      the mono-oxidized enediynes 3+ and 5+ decreased the onset temperatures
      drastically. Equally, 1-ferrocenylethynyl-2-(p-nitro-phenyl)ethynylbenzene (8)
      displayed a significant decrease in the onset temperature after oxidation to 8+.
      Because the insoluble nature of the polymeric material formed in the thermolysis
      of the oxidized enediynes prevented characterization, the origin of this drastic
      effect was studied by DFT. Contrary to expectations, one-electron oxidation does
      not lower the barrier for intramolecular cyclization. Rather, the computations
      suggest that the polymerization is initiated by a bimolecular process. 

PMID- 25397736
TI  - Augmenting the antifungal activity of an oxidizing agent with kojic Acid: control
      of penicillium strains infecting crops.
AB  - Oxidative treatment is one of the strategies for preventing Penicillium
      contamination in crops/foods. The antifungal efficacy of hydrogen peroxide (H2O2;
      oxidant) was investigated in Penicillium strains by using kojic acid (KA) as a
      chemosensitizing agent, which can enhance the susceptibility of pathogens to
      antifungal agents. Co-application of KA with H2O2 (chemosensitization) resulted
      in the enhancement of antifungal activity of either compound, when compared to
      the independent application of each agent alone. Of note, heat enhanced the
      activity of H2O2 to a greater extent during chemosensitization, whereby the
      minimum inhibitory or minimum fungicidal concentrations of H2O2 was decreased up
      to 4 or 13 fold, respectively, at 35-45  degrees C (heat), when compared to that
      at 28  degrees C (normal growth temperature). However, heat didn't increase the
      antifungal activity of KA, indicating specificity exists between heat and types
      of antifungals applied. The effect of chemosensitization was also strain
      specific, where P. expansum (both parental and fludioxonil-resistant mutants) or
      P. italicum 983 exhibited relatively higher susceptibility to the
      chemosensitization, comparing to other Penicillium strains tested. Collectively,
      chemosensitization can serve as a potent antifungal strategy to lower effective
      dosages of toxic antifungal substances, such as H2O2. This can lead to
      coincidental lowering of environmental and health risks. 

PMID- 25397735
TI  - Therapeutic targeting the cell division cycle 25 (CDC25) phosphatases in human
      acute myeloid leukemia--the possibility to target several kinases through
      inhibition of the various CDC25 isoforms.
AB  - The cell division cycle 25 (CDC25) phosphatases include CDC25A, CDC25B and
      CDC25C. These three molecules are important regulators of several steps in the
      cell cycle, including the activation of various cyclin-dependent kinases (CDKs).
      CDC25s seem to have a role in the development of several human malignancies,
      including acute myeloid leukemia (AML); and CDC25 inhibition is therefore
      considered as a possible anticancer strategy. Firstly, upregulation of CDC25A can
      enhance cell proliferation and the expression seems to be controlled through PI3K
      Akt-mTOR signaling, a pathway possibly mediating chemoresistance in human AML.
      Loss of CDC25A is also important for the cell cycle arrest caused by
      differentiation induction of malignant hematopoietic cells. Secondly, high CDC25B
      expression is associated with resistance against the antiproliferative effect of
      PI3K-Akt-mTOR inhibitors in primary human AML cells, and inhibition of this
      isoform seems to reduce AML cell line proliferation through effects on NFkappaB
      and p300. Finally, CDC25C seems important for the phenotype of AML cells at least
      for a subset of patients. Many of the identified CDC25 inhibitors show cross
      reactivity among the three CDC25 isoforms. Thus, by using such cross-reactive
      inhibitors it may become possible to inhibit several molecular events in the
      regulation of cell cycle progression and even cytoplasmic signaling, including
      activation of several CDKs, through the use of a single drug. Such combined
      strategies will probably be an advantage in human cancer treatment. 

PMID- 25397737
TI  - Ampelopsis brevipedunculata extract prevents bone loss by inhibiting
      osteoclastogenesis in vitro and in vivo.
AB  - Osteoclasts play a critical role in bone resorbing disorders such as
      osteoporosis, periodontitis, and rheumatoid arthritis. Therefore, discovery of
      agents capable of suppressing osteoclast differentiation may aid the development
      of a therapeutic access for the treatment of pathological bone loss. Ampelopsis
      brevipedunculata has been used as herbal folk medicine to treat liver diseases
      and inflammation in Asia. However, its effects on osteoclast differentiation are
      unknown. We were aimed to investigate the anti-osteoclastogenic activity in vitro
      and in vivo and to elucidate the underlying mechanism of Ampelopsis
      brevipedunculata extract (ABE). In this study, ABE inhibited receptor activator
      of NF-kappaB ligand (RANKL)-induced osteoclast differentiation, the formation of
      filamentous actin rings and the bone resorbing activity of mature osteoclasts.
      ABE inhibited RANKL-induced p38 and IkappaB phosphorylation and IkappaB
      degradation. Also, ABE suppressed the mRNA and protein expression of nuclear
      factor of activated T cells c1 (NFATc1) and c-Fos, and the mRNA expression of
      genes required for cell fusion and bone resorption, such as osteoclast-associated
      receptor (OSCAR), tartrate resistant acid phosphatase (TRAP), cathepsin K,
      dendritic cell-specific transmembrane protein (DC-STAMP), beta3-integrin and
      osteoclast stimulatory transmembrane protein (OC-STAMP). Furthermore, results of
      micro-CT and histologic analysis indicated that ABE remarkably prevented
      lipopolysaccharide (LPS)-induced bone erosion. These results demonstrate that ABE
      prevents LPS-induced bone erosion through inhibition of osteoclast
      differentiation and function, suggesting the promise of ABE as a potential cure
      for various osteoclast-associated bone diseases. 

PMID- 25397740
TI  - Best practices in developmental screening and referral for young children.
AB  - Developmental screening is recommended by the American Academy of Pediatrics as
      best practice to identify children with developmental delays. Nurse practitioners
      play a critical role in developmental screening and referral. This article
      describes best practices in developmental screening and referral resources
      available to NPs performing developmental screening.

PMID- 25397738
TI  - Effect of initial empiric antibiotic therapy combined with control of the
      infection focus on the prognosis of patients with secondary peritonitis.
AB  - BACKGROUND: In patients with intra-abdominal infection, inappropriate initial
      empiric antibiotic therapy is associated with greater morbidity. We evaluated the
      impact of adequate empiric antibiotic treatment together with control of the
      infection focus on the morbidity and mortality rates of patients with secondary
      peritonitis. METHODS: This was a prospective, observational study with the
      participation of 24 Spanish hospitals and 362 patients with secondary peritonitis
      (262 community-acquired, 100 post-operative). Therapeutic failure (infectious
      complications or death) was classified into four categories according to whether
      empiric antibiotic treatment was appropriate and the infection focus was
      controlled. RESULTS: The rates of therapeutic failure, re-operation, and
      mortality were 48%, 13%, and 8%, respectively. Empiric antibiotic treatment was
      inappropriate in 39% of cases, which was associated with a higher rate of
      surgical site infection (53% vs. 40%; p=0.031) and death (12% vs. 5%; p=0.021)
      than was observed in patients receiving appropriate initial empiric therapy.
      Eight percent of patients in whom control of the infection focus was not obtained
      suffered from more infectious complications (76% vs. 52%; p=0.01) and surgical
      site infections (69% vs. 44%; p=0.01); and in this group, both therapeutic
      failure and mortality rates were similar, independent of whether the empiric
      antibiotic therapy was appropriate. CONCLUSION: Inappropriate initial empiric
      antibiotic therapy was associated with higher rates of therapeutic failure,
      surgical site infection, re-operation, and death. Classification of therapeutic
      failure into four categories according to the appropriateness of empiric
      antibiotic therapy and the success of infection control provided excellent
      discrimination of morbidity and death.

PMID- 25397741
TI  - Ebola: the power of nursing overcomes fear.

PMID- 25397742
TI  - Missouri APRNs: overcoming scope of practice barriers.

PMID- 25397743
TI  - Integrating behavioral health: building a relationship of hope.

PMID- 25397746
TI  - Primary care management of the liver transplant patient.
AB  - There are over 65,000 people in the United States who have received a liver
      transplant. In primary care practice, nurse practitioners must be aware of the
      special considerations necessary for this population.

PMID- 25397753
TI  - Innovations and updates to the American Journal of Occupational Therapy.

PMID- 25397754
TI  - State of the journal, 2014.

PMID- 25397749
TI  - Lens subluxation after plasmin and SF6 injections in rabbit eyes.
AB  - PURPOSE: To investigate the rate of lens subluxation following plasmin and/or SF6
      injections in eyes, and whether a subsequent elevated level of vascular
      endothelial growth factor (VEGF) and vitreous tap would aggravate subluxation.
      METHODS: Four groups of rabbits were used. Group 1 received an intravitreal
      injection (IVI) of plasmin and SF6 in the right eye; group 2 received an IVI of
      plasmin in the right eye; group 3 received an IVI of SF6 in the right eye; and
      group 4 received an IVI of balanced salt solution in the right eye. After
      treatment, IVIs of VEGF were given and vitreous tap was performed three times,
      followed by clinical observation of lens subluxation and scanning electronic
      microscope evaluation of the zonular fibers. RESULTS: After IVIs of plasmin and
      SF6, and VEGF and vitreous tap had been performed one to three times, lens
      subluxation was noted in 0%, 43%, 71%, 71%, and 86% of the eyes in group 1. After
      IVIs of plasmin, VEGF, and vitreous tap had been performed one to three times,
      lens subluxation was noted in 11%, 22%, 44%, 44%, and 67% of the eyes in group 2.
      The eyes in group 3 and 4 did not show signs of lens subluxation after VEGF IVIs
      and vitreous tap. Histology confirmed zonular fiber damage in the eyes treated
      with plasmin. CONCLUSIONS: The incidence of lens subluxation increased following
      plasmin injections in the eyes, and this was aggravated by the subsequent high
      VEGF level in the eyes and vitreous tapping. Zonular fibers were disrupted
      following plasmin treatment. These effects should be kept in mind when using
      plasmin enzymes in patients with vitreoretinal abnormalities.

PMID- 25397755
TI  - Attitude, authenticity, and action: building capacity.

PMID- 25397756
TI  - Education as engine.
AB  - The pull of education is a powerful engine for societal change. Education is a
      values-driven product with specific and objective aims that serve society. The
      values of professional occupational therapy education were laid down at the
      field's inception, although they have changed with the passage of time and in
      response to the profession's and society's occupational needs. Learning is
      different from education and is an individual process that requires facilitators
      with well-honed pedagogies if it is to fuel the engine pulling the profession
      forward. Keeping occupation as the central core of the profession serves as a
      necessary filter that allows more diligent thinking and linking between
      occupation and other relevant topics. Living life to its fullest-our own lives
      and the lives of our service recipients-demonstrates progress in the
      idiosyncratic arrangement of habits and routines that are personally meaningful,
      socially satisfying, and culturally relevant. 

PMID- 25397757
TI  - Jane Case-Smith: servant-leader and scholar.

PMID- 25397759
TI  - Occupational therapy and driving and community mobility for older adults.
AB  - This special issue of the American Journal of Occupational Therapy includes
      summaries from a systematic evidence-based literature review of occupational
      therapy and driving and community mobility for older adults. Since the previous
      review on this topic in 2008, the cohort of 78 million baby boomers began turning
      65 in January 2011. As a group, this cohort is more likely to have longer life
      expectancy, stay in the workforce longer, and age in place in the community. Is
      the occupational therapy profession ready for the potential demand for driving
      rehabilitation services from this generation of older drivers who grew up with
      the automobile and are dependent on it for access to and participation in their
      communities? 

PMID- 25397760
TI  - Method for the systematic reviews on occupational therapy and driving and
      community mobility for older adults.
AB  - Systematic reviews of literature relevant to driving and community mobility for
      older adults are important to the practice of occupational therapy. We describe
      the four questions that served as the focus for the systematic reviews of the
      effectiveness of occupational therapy assessments and interventions for driving
      and community mobility for older adults. We include the background for the
      reviews; the process followed for each question, including search terms and
      search strategy; the databases searched; and the methods used to summarize and
      critically appraise the literature. The final number of articles included in each
      systematic review, a summary of the themes of the results, the strengths and
      limitations of the findings, and the implications for practice, education, and
      research are presented. 

PMID- 25397761
TI  - Occupational therapy interventions to improve driving performance in older
      adults: a systematic review.
AB  - This systematic review synthesizes the research on interventions used by
      occupational therapy practitioners to address cognitive and visual function,
      motor function, driving skills, self-regulation and self-awareness, and the role
      of passengers and family involvement in the driving ability, performance, and
      safety of older adults. After a comprehensive search of the research literature,
      29 studies were reviewed and synthesized into five themes: (1) educational
      interventions including family education, (2) cognitive-perceptual training, (3)
      interventions addressing physical fitness, (4) simulator training, and (5) behind
      the-wheel training. Outcome measures used in the studies included changes in
      knowledge through speed of processing, physical and cognitive skills predicted to
      reduce crash risk, simulated driving, and real-world driving. The studies
      demonstrated low to moderate positive effects for interventions used by
      occupational therapy practitioners to improve older driver performance. 

PMID- 25397762
TI  - Assessment tools predicting fitness to drive in older adults: a systematic
      review.
AB  - This systematic review synthesizes the research on screening and assessment tools
      used to determine older adults' fitness to drive. After a comprehensive search of
      the literature targeting tools commonly used by occupational therapists, 64
      studies were reviewed and synthesized. The evidence demonstrated that a single
      tool measuring cognition, vision, perception, or physical ability individually is
      not sufficient to determine fitness to drive. Although some tools have stronger
      evidence than others, this review supports using different and focused assessment
      tools together for specific medical conditions. Results indicate that behind-the
      wheel assessment remains the gold standard for driving evaluation; however,
      emerging evidence for observation of complex instrumental tasks of daily living
      and driving simulation supports further investigation with these tools. 

PMID- 25397763
TI  - Updated systematic review on older adult community mobility and driver licensing
      policies.
AB  - An updated systematic review of literature related to the effects of driver
      licensing policies, community mobility programs, and driving cessation programs
      on older adult performance and participation was completed as a part of the
      American Occupational Therapy Association's Evidence-Based Literature Review
      Project. The results revealed that relicensing policies instituted by states
      yield inconsistent results in terms of reducing traffic crashes, traffic
      violations, and traffic-related fatalities. The evidence related to community
      mobility and driving cessation programs has suggested that programming to support
      the transition from driving to other modes of mobility can be beneficial for
      older adults and their family members. In addition, community contexts that are
      supportive of pedestrian travel significantly increase this mode of mobility.
      This evidence-based review informs occupational therapy practice and suggests
      that increased therapeutic attention should be directed toward supportive
      transitions from driving and sustaining community mobility for optimal engagement
      and participation. 

PMID- 25397764
TI  - Effects of a classroom-embedded occupational therapist-teacher handwriting
      program for first-grade students.
AB  - This study examined the effectiveness of Write Start, a handwriting and writing
      program cotaught by teachers and occupational therapists for first-grade
      children. Four classrooms (n = 80) received the Write Start program, and four (n
      = 58) received standard handwriting and writing instruction. Two teachers and an
      occupational therapist implemented the 24-session manualized program, which
      included station teaching and individualized supports. The program emphasized
      practice in small groups in which the coteaching team provided students with
      frequent feedback, encouraged self-evaluation, and facilitated peer modeling and
      peer evaluation. Students who completed the Write Start program improved more in
      handwriting legibility and speed than the group receiving standard instruction.
      Writing fluency and written composition were no different between groups at
      posttest; however, writing fluency was significantly higher for Write Start
      students at 6-mo follow-up. Write Start students with low legibility at baseline
      made significant improvements, suggesting that the program may benefit students
      at risk for handwriting and writing problems. 

PMID- 25397765
TI  - Evaluation of a pilot parent-delivered play-based intervention for children with
      attention deficit hyperactivity disorder.
AB  - OBJECTIVE. This study evaluated a parent-delivered intervention aiming to address
      the social difficulties of children with attention deficit hyperactivity disorder
      (ADHD). The intervention was evaluated from three perspectives: effectiveness,
      feasibility, and appropriateness. METHOD. This one-group pretest-posttest study
      included 5 children with ADHD and their parents, who had previously participated
      in a therapist-delivered play-based intervention. The 7-wk parent-delivered
      intervention involved home modules (including a DVD, manual, and play dates with
      a typically developing playmate) and three therapist-led clinic-based play
      sessions. The Test of Playfulness was used as a pre- and postintervention and
      follow-up measure. Parents were interviewed 1 mo following the intervention, and
      data were analyzed for recurring themes. RESULTS. Children's social play outcomes
      improved significantly from pretest to 1-mo follow-up (Z = 2.02, p = .04, d =
      1.0). Three themes emerged: the clinic play environment as a sanctuary, parental
      barriers to intervention delivery, and tools for repeating learned lessons.
      CONCLUSION. The parent-delivered intervention demonstrated preliminary evidence
      for feasibility and effectiveness. Further research is warranted regarding
      appropriateness. 

PMID- 25397766
TI  - Psychometrics of the Home Safety Self-Assessment Tool (HSSAT) to prevent falls in
      community-dwelling older adults.
AB  - OBJECTIVE. To identify psychometric properties of the Home Safety Self-Assessment
      Tool (HSSAT) to prevent falls in community-dwelling older adults. METHOD. We
      tested content validity, test-retest reliability, interrater reliability,
      construct validity, convergent and discriminant validity, and responsiveness to
      change. RESULTS. The content validity index was .98, the intraclass correlation
      coefficient for test-retest reliability was .97, and the interrater reliability
      was .89. The difference on identified risk factors between the use and nonuse of
      the HSSAT was significant (p = .005). Convergent validity with the Centers for
      Disease Control and Prevention Home Safety Checklist was high (r = .65), and
      discriminant validity with fear of falling was very low (r = .10). The
      responsiveness to change was moderate (standardized response mean = 0.57).
      CONCLUSION. The HSSAT is a reliable and valid instrument to identify fall risks
      in a home environment, and the HSSAT booklet is effective as educational material
      leading to improvement in home safety. 

PMID- 25397767
TI  - Validating the measurement of executive functions in an occupational context for
      adults with attention deficit hyperactivity disorder.
AB  - OBJECTIVE. The objectives of this study were to better understand the cognitive
      profile of adults with attention deficit hyperactivity disorder (ADHD), their
      occupational performance, and their quality of life (QoL) and to examine the
      validity of a cognitive-functional evaluation (CFE) battery for these adults.
      METHOD. Eighty-one adults with ADHD and 58 without ADHD completed ADHD symptom
      ratings, the Behavior Rating Inventory of Executive Function-Adult Version, and
      the Adult ADHD Quality-of-Life Scale. An occupational performance interview was
      administered to the ADHD group. RESULTS. A broad range of occupational concerns
      were reported. We found significant differences between groups on all measures.
      In the ADHD group, we found medium significant correlations among the measures.
      CONCLUSION. Adults with ADHD experience cognitive and functional difficulties in
      their daily lives associated with QoL. The results support the use of a CFE
      battery that has been shown to be sensitive and specific for these adults. 

PMID- 25397768
TI  - Effect of an occupation-focused family intervention on change in parents' time
      use and children's body mass index.
AB  - OBJECTIVE. This study explored factors related to changes in the time parents
      spent with their children with obesity and associated decreases in children's
      body mass index (BMI) z-scores after an occupation-focused intervention. METHOD.
      Parents participated in a 1-yr occupation-focused intervention to promote healthy
      family lifestyles. Data on 40 parents of 22 children with obesity ages 4-6 yr
      were collected before and after intervention and analyzed using linear and
      multiple regression methods. RESULTS. Parents increased time spent with their
      children by an average of 91 min/day. Parents' finances, perceived satisfaction
      in daily occupations, low BMI, and mastery at inclusion were associated with
      increased time spent with their children. Mothers' subjective health and high
      mastery and fathers' perceived occupational value and education explained 67% of
      the variance in children's BMI z-scores. CONCLUSION. The results indicate
      important factors to consider in developing interventions that facilitate
      occupational engagement and health among children with obesity and their
      families. 

PMID- 25397769
TI  - Drawing Proficiency Screening Questionnaire (DPSQ): development, reliability, and
      validity.
AB  - OBJECTIVE. We describe the development and preliminary psychometric examination
      of the DPSQ for identifying drawing difficulties in preschool children. METHOD.
      Teachers completed the DPSQ for 78 children ages 3-6 yr from 4 preschools.
      Children drew age-appropriate geometric forms of the Visual-Motor Integration
      (VMI) test on a digitizing tablet. We examined psychometric properties of the
      DPSQ and analyzed group membership. RESULTS. Internal consistency was high (alpha
      = .82). Significant correlations were found between DPSQ and VMI scores
      indicating in-air time (r = .37, p = .002) and pressure on the writing tool (r =
      .32, p = .007). The typical and at-risk groups differed significantly in VMI and
      DPSQ scores, t(76) = 5.6, p = .001. The DPSQ mean score differentiated between
      76% of children with and without visual-motor deficits. CONCLUSION. The DPSQ is a
      useful tool for teachers and occupational therapy practitioners for indicating
      visual-motor deficits and potential handwriting problems. 

PMID- 25397770
TI  - National survey of occupational therapy practitioners' involvement in response to
      intervention.
AB  - OBJECTIVE. We sought to describe occupational therapy practitioners' perceived
      levels of preparedness for and involvement in school-based Response to
      Intervention (RtI) initiatives. METHOD. We mailed a survey to a random sample of
      1,000 practitioners from the American Occupational Therapy Association's Early
      Intervention and School Systems Special Interest Section. RESULTS. Of 295
      returned surveys (29.9% response rate), 19 were excluded because of missing or
      incomplete data. Three-quarters of respondents (77.6%) reported that their
      districts implemented RtI. Two-thirds of respondents (66.3%) indicated that lack
      of resources limited their involvement in RtI; two-thirds (67%) said that
      district guidelines that describe expectations for practitioners' involvement
      would help increase their participation. Many respondents cited the need for
      continuing education and supported moving from a caseload to a workload model.
      CONCLUSION. Occupational therapy practitioners would benefit from specific
      district guidelines outlining the services they are able to provide within the
      context of RtI. 

PMID- 25397771
TI  - Development of additional tasks for the executive function performance test.
AB  - OBJECTIVE. The Executive Function Performance Test (EFPT) is a reliable and valid
      performance-based assessment of executive function for people with stroke. The
      objective of this study was to enhance the clinical utility of the EFPT by
      developing and testing additional tasks for the EFPT in the Alternate EFPT
      (aEFPT). METHOD. We performed a cross-sectional study with poststroke
      participants (n = 25) and healthy control participants (n = 25). All participants
      completed a neuropsychological assessment battery and both the EFPT and the
      aEFPT. RESULTS. No statistically significant differences were found between the
      EFPT and the aEFPT when examining total scores, construct scores, and two overall
      task scores. Correlations between the aEFPT and the neuropsychological measures
      were adequate to strong (r2s = .59-.83). CONCLUSION. The aEFPT tasks are
      comparable to the original EFPT tasks, providing occupational therapy
      practitioners with additional tasks that can be used clinically to identify
      performance-based executive function deficits in people with stroke. 

PMID- 25397772
TI  - Update on productive aging research in the American Journal of Occupational
      Therapy, 2013, and overview of research published 2009-2013.
AB  - In light of the Centennial Vision charge of supporting practice through evidence,
      this article reviews productive aging research published in the American Journal
      of Occupational Therapy (AJOT) in 2013 and as a whole from 2009 to 2013. Thirteen
      such articles were published in 2013, consisting of 4 systematic reviews that
      identified effective occupational therapy interventions for older adults with low
      vision; 1 randomized controlled trial that examined changes in occupational
      therapists' mental health practices with DVD training; and 8 descriptive articles
      addressing instrument development, practitioner decision making, patient
      management of medications, and effects of task activities on pain and
      participation levels. From 2009 to 2013, the quantity and quality of AJOT
      articles on productive aging increased; 63 articles were published, including 24
      effectiveness studies, 14 basic research studies, 15 articles on instrument
      development and testing, 1 article linking occupational engagement and health, 6
      articles on professional education, and 3 articles addressing professional
      questions. 

PMID- 25397773
TI  - Prediction of metabolic flux distribution from gene expression data based on the
      flux minimization principle.
AB  - Prediction of possible flux distributions in a metabolic network provides
      detailed phenotypic information that links metabolism to cellular physiology. To
      estimate metabolic steady-state fluxes, the most common approach is to solve a
      set of macroscopic mass balance equations subjected to stoichiometric constraints
      while attempting to optimize an assumed optimal objective function. This
      assumption is justifiable in specific cases but may be invalid when tested across
      different conditions, cell populations, or other organisms. With an aim to
      providing a more consistent and reliable prediction of flux distributions over a
      wide range of conditions, in this article we propose a framework that uses the
      flux minimization principle to predict active metabolic pathways from mRNA
      expression data. The proposed algorithm minimizes a weighted sum of flux
      magnitudes, while biomass production can be bounded to fit an ample range from
      very low to very high values according to the analyzed context. We have
      formulated the flux weights as a function of the corresponding enzyme reaction's
      gene expression value, enabling the creation of context-specific fluxes based on
      a generic metabolic network. In case studies of wild-type Saccharomyces
      cerevisiae, and wild-type and mutant Escherichia coli strains, our method
      achieved high prediction accuracy, as gauged by correlation coefficients and sums
      of squared error, with respect to the experimentally measured values. In contrast
      to other approaches, our method was able to provide quantitative predictions for
      both model organisms under a variety of conditions. Our approach requires no
      prior knowledge or assumption of a context-specific metabolic functionality and
      does not require trial-and-error parameter adjustments. Thus, our framework is of
      general applicability for modeling the transcription-dependent metabolism of
      bacteria and yeasts. 

PMID- 25397774
TI  - Reporting quality of systematic reviews/meta-analyses of acupuncture.
AB  - BACKGROUND: The QUOROM and PRISMA statements were published in 1999 and 2009,
      respectively, to improve the consistency of reporting systematic reviews
      (SRs)/meta-analyses (MAs) of clinical trials. However, not all SRs/MAs adhere
      completely to these important standards. In particular, it is not clear how well
      SRs/MAs of acupuncture studies adhere to reporting standards and which reporting
      criteria are generally ignored in these analyses. OBJECTIVES: To evaluate
      reporting quality in SRs/MAs of acupuncture studies. METHODS: We performed a
      literature search for studies published prior to 2014 using the following public
      archives: PubMed, EMBASE, Web of Science, the Cochrane Database of Systematic
      Reviews (CDSR), the Chinese Biomedical Literature Database (CBM), the Traditional
      Chinese Medicine (TCM) database, the Chinese Journal Full-text Database (CJFD),
      the Chinese Scientific Journal Full-text Database (CSJD), and the Wanfang
      database. Data were extracted into pre-prepared Excel data-extraction forms.
      Reporting quality was assessed based on the PRISMA checklist (27 items). RESULTS:
      Of 476 appropriate SRs/MAs identified in our search, 203, 227, and 46 were
      published in Chinese journals, international journals, and the Cochrane Database,
      respectively. In 476 SRs/MAs, only 3 reported the information completely. By
      contrast, approximately 4.93% (1/203), 8.81% (2/227) and 0.00% (0/46) SRs/Mas
      reported less than 10 items in Chinese journals, international journals and CDSR,
      respectively. In general, the least frequently reported items (reported<=50%) in
      SRs/MAs were "protocol and registration", "risk of bias across studies", and
      "additional analyses" in both methods and results sections. CONCLUSIONS: SRs/MAs
      of acupuncture studies have not comprehensively reported information recommended
      in the PRISMA statement. Our study underscores that, in addition to focusing on
      careful study design and performance, attention should be paid to comprehensive
      reporting standards in SRs/MAs on acupuncture studies.

PMID- 25397775
TI  - Myocardial metastases on 6-[18F] fluoro-L-DOPA PET/CT: a retrospective analysis
      of 116 serotonin producing neuroendocrine tumour patients.
AB  - PURPOSE: This study evaluates the prevalence of cardiac metastases in patients
      with serotonin producing neuroendocrine tumours (NET), examined with 18F-FDOPA
      PET/CT, and the relationship of these metastases to the presence of carcinoid
      heart disease (CHD) based on echocardiography. BACKGROUND: CHD occurs in patients
      with serotonin producing NET. The diagnostic method of choice remains
      echocardiography. The precise prevalence of cardiac metastases is unknown given
      the limitations of standard technologies. Nuclear medicine modalities have the
      potential to visualize metastases of NET. METHODS: All patients who underwent 18F
      FDOPA PET/CT because of serotonin producing NET between November 2009 and May
      2012 were retrospectively analyzed. The presence of cardiac metastasis was
      defined as myocardial tracer accumulation higher than the surrounding
      physiological myocardial uptake. Laboratory tests and transthoracic
      echocardiography (TTE) results were digitally collected. RESULTS: 116 patients
      (62 male) underwent 18F-FDOPA PET/CT, mean age was 61+/-13 years. TTE was
      performed in 79 patients. Cardiac metastases were present in 15 patients, of
      which 10 patients also underwent TTE. One patient had both cardiac metastasis
      (only on 18F-FDOPA PET/CT) and echocardiographic signs of CHD. There were no
      differences in echocardiographic parameters for CHD between patients with and
      without cardiac metastases. TTE in none of the 79 patients showed cardiac
      metastases. CONCLUSION: The prevalence of cardiac metastases detected with 18F
      FDOPA PET/CT in this study is 13%. 18F-FDOPA PET/CT can visualize cardiac
      metastases in serotonin producing NET patients. There appears to be no
      relationship between the presence of cardiac metastases and TTE parameters of
      CHD.

PMID- 25397777
TI  - Doping of C70 fullerene peapods with lithium vapor: Raman spectroscopic and Raman
      spectroelectrochemical studies.
AB  - Raman spectroscopy and in situ Raman spectroelectrochemistry were applied to
      study the lithium vapor doping of C70@SWCNTs (peapods). A strong degree of doping
      was proved by the vanishing of the single walled carbon nanotubes (SWCNT's)
      radial breathing mode (RBM) and by the attenuation of the tangential (TG) band
      intensity. In contrast to potassium vapor doping, the strong downshift of the
      frequency of the TG band has not been observed for Li-doping. The Li vapor
      treated peapods remained partly doped even if they were exposed to humid air.
      This has been reflected by a reduced intensity of the nanotube and the fullerene
      modes and by the change of the shape of the RBM band as compared to that of the
      undoped sample. The modes of the intratubular fullerene were almost unresolved
      after the contact of the Li-doped sample with water. A lithium insertion into the
      interior of a peapod and its strong interaction with the intratubular fullerene
      is suggested to be responsible for the air-insensitive residual doping. This
      residual doping was studied by spectroelectrochemical measurements. The TG band
      of the Li doped peapods is partly upshifted during the anodic doping, which
      points to the different state of C70@SWCNTs and C60@SWCNTs studied previously. 

PMID- 25397776
TI  - Anti-atherogenic effect of hydrogen sulfide by over-expression of cystathionine
      gamma-lyase (CSE) gene.
AB  - Hydrogen sulfide (H2S) is an important gaseous signaling molecule that functions
      in physiological and pathological conditions, such as atherosclerosis. H2S
      dilates vessels and therefore has been suggested as an anti-atherogenic molecule.
      Since cystathionine gamma-lyase (CSE) enzyme is responsible for producing H2S in
      the cardiovascular system, we hypothesized that up-regulation of CSE expression
      in vivo with preservation of H2S bioactivity can slow down plaque formation and,
      can serve as a therapeutic strategy against atherosclerosis. In this study,
      C57BL/6 wild type mice (WT), ApoE knockout mice (KO) and transgenic ApoE knockout
      mice overexpressing CSE (Tg/KO) at four weeks of age were weaned. They were then
      fed with either normal or atherogenic diet for 12 weeks. At week 16, serial
      plasma lipid levels, body weight, and blood pressure were measured prior to
      euthanization of the mice and the size of atherosclerotic plaques at their aortic
      roots was measured. Tg/KO mice showed an increase in endogenous H2S production in
      aortic tissue, reduced atherosclerotic plaque sizes and attenuation in plasma
      lipid profiles. We also showed an up-regulation in plasma glutathionine
      peroxidase that could indicate reduced oxidative stress. Furthermore, there was
      an increase in expression of p-p53 and down regulation of inflammatory nuclear
      factor-kappa B (NF-kappaB) in aorta. To conclude, alteration of endogenous H2S by
      CSE gene activation was associated with reduced atherosclerosis in ApoE-deficient
      mice. Up-regulation of CSE/H2S pathway attenuates atherosclerosis and this would
      be a potential target for therapeutic intervention against its formation. 

PMID- 25397778
TI  - The cerebellum in eye movement control: nystagmus, coordinate frames and
      disconjugacy.
AB  - In this review we discuss several aspects of eye movement control in which the
      cerebellum is thought to have a key role, but have been relatively ignored. We
      will focus on the mechanisms underlying certain forms of cerebellar nystagmus, as
      well as the contributions of the cerebellum to binocular alignment in healthy and
      diseased states. A contemporary review of our understanding provides a basis for
      directions of further inquiry to address some of the uncertainties regarding the
      contributions of the cerebellum to ocular motor control. 

PMID- 25397779
TI  - Fellow eye effect of unilateral intravitreal anti-VEGF injections in eyes with
      diabetic macular edema.

PMID- 25397780
TI  - Re: 'Fellow eye effect of unilateral intravitreal bevacizumab injection in eyes
      with diabetic macular edema'.

PMID- 25397781
TI  - Is accelerated corneal cross-linking for keratoconus the way forward? Yes or No.

PMID- 25397782
TI  - Is intermittent exotropia a curable condition?
AB  - Surgical treatment of childhood intermittent exotropia (XT) is associated with
      high recurrence rates. In addition, the natural history of intermittent XT has
      not been rigorously studied and, anecdotally, some cases resolve without surgery.
      We compared long-term cure rates in children with surgically and non-surgically
      managed intermittent XT. Children undergoing surgery for intermittent XT who had
      5 years follow-up were retrospectively identified. A non-surgical cohort of
      comparable children was selected by matching each surgical patient for age at
      onset and age at the 5-year examination. Cure was defined as no manifest tropia
      on examination or by history, no new monofixation (stereoacuity subnormal for
      age), and no additional surgery. Each group had 33 children (total follow-up from
      presentation 7.2+/-2.6 years in the surgical group vs 6.8+/-2.3 years). There
      were no significant differences between groups for age at onset, age at
      presentation, or distance or near angle of deviation at presentation (all
      P>=0.4). The cure rate at 5 years was 30% in the surgical group and 12% in the
      non-surgical group (P=0.1; difference 18%, 95% CI -1 to 37%). Only a small
      proportion of surgical and non-surgical patients met our definition of cure, with
      the vast majority demonstrating a constant or intermittent manifest deviation
      after an average of 7 years follow-up. In childhood intermittent XT, long-term
      cure is difficult to achieve with surgical intervention, and in some patients
      managed non-surgically the intermittent XT will spontaneously resolve. 

PMID- 25397783
TI  - Eye movements and their functions in everyday tasks.
AB  - Human saccades and fixations have numerous functions in complex everyday tasks,
      which have sometimes been neglected in simple experimental situations. In this
      review I describe some of the characteristics of eye movement behaviour during
      real-world interactions with objects, while walking in natural environments and
      while holding a conversation. When performing real-world actions and walking
      around the world, we fixate relevant features at critical time points during the
      task. The eye movements between these fixations are planned and coordinated
      alongside head and body movements, often occurring a short time before the
      corresponding action. In social interactions, eye movements are both a mechanism
      for taking in information (for example, when looking at someone's face or
      following their gaze) and for signalling one's attention to another person. Thus
      eye movements are specific to a particular task context and subject to high-level
      planning and control during everyday actions. 

PMID- 25397784
TI  - Visual outcome and incidence of glaucoma in patients with microspherophakia.
AB  - INTRODUCTION: A number of ocular complications have been reported in
      microspherophakia. The literature however is limited to small case reports and
      the incidence of these complications is largely unknown. Our study describes a
      series of patients who presented to our hospital from 1998 to 2008. MATERIAL AND
      METHODS: Data on the clinical and surgical findings of patients presented to us
      from 1998 to 2008 with microspherophakia were retrieved from the medical records
      and the results analyzed. RESULTS: Thirty-six eyes of 18 patients were reviewed.
      The mean age at presentation was 16+/-10 years. All patients had varying degrees
      of lenticular myopia with a mean of -11.07+/-5.03 D. Glaucoma developed in 16
      eyes (44.4%). Half of them had high IOP at presentation. Despite medical and
      surgical management IOP remained high in five eyes at the last follow-up. Sixteen
      eyes (44.4%) required lensectomy for dislocated crystalline lens. Lensectomy did
      not have any impact on the intraocular pressures. Homocysteinuria was the most
      common systemic association noted. CONCLUSION: Microspherophakia is associated
      with a high incidence of lenticular myopia, subluxation of the crystalline lens
      and glaucoma. Management of glaucoma is difficult with the IOP remaining high in
      spite of combined medical and surgical management.

PMID- 25397785
TI  - How does the structure of extraocular muscles and their nerves affect their
      function?
AB  - The sensory and motor control of human extraocular muscles (EOMs) have been
      subjected to considerable speculation in ophthalmic literature, often related to
      infranuclear structures such as the unique complement of muscle fibres and their
      associated sensory organs. The intrafusal fibres do not resemble their somatic
      counterparts and their peculiar morphology has raised questions about their
      proprioceptive capacity. No Golgi tendon organs have so far been observed and the
      myotendinous nerve endings, previously assumed to convey sensory information,
      have recently been argued to merely represent constituents of the efferent
      innervation serving the multiply innervated muscles fibres. These observations
      raise questions about the overall capacity to monitor the activity created by the
      generous efferent nerve supply observed in these muscles. Furthermore, the argued
      independent activity of muscular layers and compartments suggest that the
      required feedback must be highly structured and more specific than previously
      assumed. Yet, uncertainty about the source of such information remains. The
      purpose of this paper is to provide a short review of neuromuscular properties of
      human extraocular muscles. Their functional implications and the most reputable
      sources of proprioception will also be discussed. The promoted views are based on
      pertinent literature and previous research undertaken by the authors. 

PMID- 25397786
TI  - Response to O'Brart: 'Is accelerated cross-linking the way forward? Yes or No'.

PMID- 25397787
TI  - Reliability of vitreous histological detection of pathogenic fungi in the
      diagnosis of fungal endophthalmitis.
AB  - PURPOSE: To assess the value of histopathologic investigations of vitreous biopsy
      specimens in the diagnosis of fungal endophthalmitis compared with that of
      conventional smear and fungal culture. METHODS: In this prospective study, 10
      patients with clinically suspected fungal endophthalmitis of any etiology
      underwent intravitreal sampling and vitrectomy for diagnostic and therapeutic
      purposes. Infused vitreous biopsy samples were centrifuged and mixed with blood
      serum for hematoxylin and eosin and periodic-acid Schiff staining, whereas the
      remaining samples were submitted for smear and fungal culture. All slides were
      reviewed by an attending pathologist. RESULTS: Vitreous specimens were obtained
      from 10 eyes of 10 patients. Positive histological diagnoses of fungal
      endophthalmitis from vitreous biopsies were made in seven cases (70%). The
      sensitivity of histological detection of fungi was higher than conventional smear
      (50%) or culture (40%); all these techniques are complementary. CONCLUSIONS:
      Specific histopathological detection of pathogenic fungi in clinical vitreous
      specimens could be helpful for the diagnosis of suspected fungal endophthalmitis.
      Positive histopathology results were seen in the majority of samples; however,
      difficulties in determining related fungal etiology limit its application.

PMID- 25397789
TI  - Distance-near disparity esotropia: can we shrink the gap?
AB  - Distance-near disparity esotropias are a group of heterogenous usually acquired
      strabismus disorders, where the angle of misalignment at near exceeds that at
      distance by 10 prism diopters or more, where the accurate correction of
      refractive errors and ambylopia are important early objectives. These
      aetiologically diverse entities respond non-uniformally to strabismus surgery and
      bifocals. The management challenge is one of 'shrinking' the disparity so that
      the affected individuals can develop and comfortably maintain binocular single
      vision and/or optimal alignment. Surgical procedures have continued to evolve but
      none of the current operative procedures are superior for all patients.
      Subclassifying this strabismus and highlighting publication data from more
      homogenous clinical series may assist with the optimisation of future management
      and treatment outcomes. 

PMID- 25397788
TI  - Clinical outcomes between optical path difference custom aspheric treatment and
      optimized prolate ablation photorefractive keratectomy in myopia exceeding 8
      diopters.
AB  - PURPOSE: Comparison of visual acuity, refractive, and wavefront outcomes
      associated with optimized prolate ablation (OPA) and optical path difference
      custom aspheric treatment (OPDCAT) algorithms for correction of myopia exceeding
      8 diopters (D). PATIENTS AND METHODS: Patients were randomly assigned to have
      photorefractive keratectomy (PRK) with OPA (n=32) or OPDCAT (n=21) algorithms.
      Visual acuity, manifest refraction, ocular and corneal higher-order aberrations,
      corneal asphericity, modulated-transfer function, and point-spread function were
      compared 1, 3, and 6 months postoperatively. RESULTS: Mean manifest-refraction
      spherical equivalents at 6 months were -0.24 D in both groups. All patients in
      both groups had an uncorrected-distance visual acuity of 20/20 or better.
      Predictability (+/-1 D from intended refraction) at 6 months was 94% in the OPA
      group, and in the OPDCAT group it was 86%. The OPA group had less induced corneal
      and ocular spherical aberrations (SAs) than the OPDCAT group. Postoperative
      corneal asphericity change was lowest in the OPA group. Both the groups exhibited
      significantly-improved AreaRatio-Total value and insignificantly deteriorated
      AreaRatio-HO value throughout the postoperative period. The OPA group had
      significantly-higher AreaRatio-Total compared with OPDCAT group at both 1 and 6
      months after the operation. Six months after surgery, the Strehl ratio had
      decreased in both groups, and there was no significant difference between the
      groups. CONCLUSION: The OPA algorithms yielded higher-objective visual quality
      and predictability, induced less corneal and ocular SAs, and preserved more
      preoperative-corneal asphericity than the OPDCAT algorithms.

PMID- 25397790
TI  - Assessment of the correlation between implant stability and bone density by
      computed tomography and resonance frequency analysis in fresh cadavers.
AB  - PURPOSE: Because of the immediate loading implant process, clinicians must
      consider implant primary stability issues before initiating surgery. The aim of
      this study was to assess the correlation between the bone density assessed by
      computed tomography (CT) images and the primary stability of two implant designs,
      as determined by resonance frequency analysis (RFA). MATERIALS AND METHODS: Sixty
      implants (30 NobelActive, 30 NobelSpeedy [Nobel Biocare]) were placed in five
      totally edentulous fresh cadaver maxillae. Before surgery, CT images were
      analyzed and bone densities measured. Implant primary stabilities (measured in
      implant stability quotient [ISQ] units) were determined along the buccolingual
      and mesiodistal axes by RFA. Correlations were assessed using the Pearson
      correlation test. RESULTS: Bone densities were similar near NobelActive and
      NobelSpeedy implants: 434.67 (+/- 220.53) versus 479.87 (+/- 209.05) Hounsfield
      Units (HU). Bone densities and NobelActive primary stabilities were highly
      correlated with rho = 0.74 (P = .000) and rho = 0.78 (P = .000) for the
      buccolingual and mesiodistal axes, respectively. An association was found between
      the 350 HU and 50 ISQ values, confirming good primary stabilities. For
      NobelSpeedy implants, no correlation was found regardless of the axis, with rho =
      -0.07 (P = .72) (buccolingual) and rho = -0.10 (P = .59) (mesiodistal). However,
      poor and good stabilities were observed in the anterior and posterior areas,
      respectively. CONCLUSION: This study revealed variations in primary stabilities
      depending on the implant design. The primary stability of conical implants with a
      double-lead thread design (NobelActive) seemed bone density-dependent regardless
      of the area of the maxilla, whereas the primary stability of nearly parallel-wall
      implants with a classical thread design (NobelSpeedy) seemed dependent on
      anatomical morphology. These results raise questions about the specific roles of
      the implant shape and thread design depending on the bone density and alveolar
      morphology.

PMID- 25397791
TI  - History of periodontitis as a risk factor for long-term survival of dental
      implants: a meta-analysis.
AB  - PURPOSE: The authors conducted a meta-analysis to determine the effect of a
      history of periodontitis on the long-term survival of dental implants. MATERIALS
      AND METHODS: An electronic search of PubMed and a supplemental manual search were
      conducted. Studies published in English through March 2013 were included in the
      meta-analysis. Survival rates, success rates, periodontal status, types of
      periodontitis, most recent follow-up time, and other information were extracted
      and analyzed. RESULTS: Thirteen studies involving 2,011 patients and 6,802
      implants were included in the meta-analysis. The results revealed that a history
      of periodontitis, especially aggressive periodontitis, is associated with
      significantly higher risks of long-term implant failure versus a healthy
      periodontium (risk ratio [RR] = 1.03, 95% confidence interval [CI] = 1.02 to
      1.04). Based on the limited number of included articles, a subgroup analysis
      showed that a history of periodontitis had no statistically significant effect on
      implant survival up to 100 months of follow-up (RR = 1.03, 95% CI = 0.99 to
      1.06); however, it did significantly affect implant survival within a period of
      101 to 200 months (RR = 1.03, 95% CI = 1.02 to 1.04). Some implant systems also
      significantly influenced the correlation between a history of periodontitis and
      implant survival. CONCLUSION: Within the limitations of this meta-analysis, a
      history of periodontitis is estimated to be a statistical risk factor for the
      long-term survival of dental implants. This negative effect would be most evident
      in patients with aggressive periodontitis, severe periodontitis, or after a
      longer follow-up.

PMID- 25397792
TI  - Displacement of screw-retained splinted and nonsplinted restorations into
      implants with conical internal connections.
AB  - PURPOSE: Variable abutment displacement could potentially affect proximal
      contacts, incisal edge position, or occlusion of implant-supported prostheses.
      This study aimed to measure and compare displacements of splinted and nonsplinted
      restorations into implants featuring internal conical connections as screws were
      tightened by hand or by torque driver. MATERIALS AND METHODS: A stereolithic
      resin model was printed using computed tomography data from a patient missing
      mandibular left first and second molars. Two 5.0 * 11-mm implants were placed in
      the edentulous site using a surgical guide. Two sets (splinted and nonsplinted)
      of gold screw-retained prostheses were made indirectly to fit the implants in the
      stereolithic model representing the patient. The axial position of the crowns
      relative to a fixed location on the model was recorded following hand tightening
      using the three-dimensional image correlation technique and image correlation
      software. A pair of high-resolution digital cameras provided a synchronized view
      of the model during the experiment. Relative crown positions were again recorded
      after tightening with a torque driver to 25 Ncm. Testing was repeated randomly
      three times for each set of crowns. Displacement data after torque tightening
      were compared using a factorial analysis of variance with JMP 9.0 software (SAS)
      followed by a Tukey-Kramer post hoc test (alpha = .05). Interproximal contacts
      were evaluated using an 8-MUm tin foil shim after tightening by hand and torque
      driver. RESULTS: Displacements for splinted and nonsplinted restorations differed
      only in a buccal direction. The nonsplinted crowns displaced significantly more
      than splinted crowns. Discernible differences were observed for the tin foil shim
      when dragged through proximal contacts following hand versus torque tightening.
      CONCLUSION: Differences between screw tightening by hand or torque driver should
      be taken into consideration during laboratory and clinical adjustments to prevent
      esthetic and functional complications.

PMID- 25397793
TI  - Role of photofunctionalization in mitigating impaired osseointegration associated
      with type 2 diabetes in rats.
AB  - PURPOSE: Peri-implant osteogenesis is reported to be impaired in patients with
      diabetes. The current study tested the hypothesis that ultraviolet (UV) treatment
      of titanium, or photofunctionalization, is able to mitigate the impaired
      osseointegration associated with type 2 diabetes. MATERIALS AND METHODS:
      Untreated and photofunctionalized titanium implants were placed into the femurs
      of genetically modified rats with a close phenotypic resemblance to human type 2
      diabetes, as characterized by late-onset hyperglycemia and obesity. Implants were
      photofunctionalized with UV light for 15 minutes immediately before placement.
      The strength of osseointegration was evaluated using a biomechanical push-in
      test, and the tissue-implant interface was examined using scanning electron
      microscopy and energy-dispersive spectroscopy. RESULTS: Photofunctionalization
      converted implants from hydrophobic to superhydrophilic. Photofunctionalization
      induced hemophilicity was also confirmed during surgery. The strength of
      osseointegration of photofunctionalized implants was significantly greater than
      that of untreated implants, by 1.8 and 3 times, at weeks 2 and 4 of healing,
      respectively. Osseointegration of photofunctionalized implants in diabetic
      animals was even stronger than that of untreated implants placed in normal
      animals throughout the healing period. Photofunctionalized implants placed in
      diabetic rats were extensively covered with calcium- and phosphorus-rich tissue
      that masked the titanium signal. CONCLUSION: Photofunctionalization accelerated
      and enhanced levels of osseointegration and overcame impaired osseointegration in
      a rat model of type 2 diabetes. Further prospective studies are warranted to
      establish the clinical efficacy of photofunctionalization in patients with
      diabetes.

PMID- 25397794
TI  - Incidence of anatomical variations and disease of the maxillary sinuses as
      identified by cone beam computed tomography: a systematic review.
AB  - PURPOSE: To analyze available evidence on the incidence of anatomical variations
      or disease of the maxillary sinuses as identified by cone beam computed
      tomography (CBCT) in dentistry. MATERIALS AND METHODS: A focused question was
      developed to search the electronic databases MEDLINE, EMBASE, the Cochrane Oral
      Health Group Trials Register, and CENTRAL and identify all relevant papers
      published between 1980 and January 19, 2013. Unpublished literature at
      ClinicalTrials.gov, in the National Research Register, and in the Pro-Quest
      Dissertation Abstracts and Thesis database was also included. Studies were
      included irrespective of language. These results were supplemented by hand and
      gray literature searches. RESULTS: Twenty-two studies were identified. Twenty
      were retrospective cohort studies, one was a prospective cohort study, and one
      was a case control study. The main indication for CBCT was dental implant
      treatment planning, and the majority of studies used a small field of view for
      imaging. The most common anatomical variations included increased thickness of
      the sinus membrane, the presence of sinus septa, and pneumatization. Reported
      sinus disease frequency varied widely, ranging from 14.3% to 82%. There was a
      wide range in the reported prevalence of mucosal thickening related to apical
      pathology, the degree of lumenal opacification, features of sinusitis, and the
      presence of retention cysts and polyps. More pathologic findings in the maxillary
      sinus were reported in men than in women, and the medial wall and sinus floor
      were most frequently affected. CONCLUSION: CBCT is used primarily to evaluate
      bony anatomy and to screen for overt pathology of the maxillary sinuses prior to
      dental implant treatment. Differences in the classification of mucosal findings
      are problematic in the consistent and valid assessment of health and disease of
      the maxillary sinus.

PMID- 25397795
TI  - The effect of a biphasic calcium phosphate on bone healing: a pilot study in
      rats.
AB  - PURPOSE: The primary objective of this pilot study was to evaluate the
      effectiveness of biphasic calcium phosphate (BCP) covered with a polyethylene
      glycol (PEG) membrane in the regeneration of 5-mm-diameter defects created in the
      calvaria of Wistar rats and compare this with the regeneration of defects covered
      only with the PEG membrane. MATERIALS AND METHODS: Two 5-mm-diameter parietal
      defects were created in seven Wistar rats. The control defect in the left
      parietal bone was covered with an experimental PEG membrane (Straumann
      MembraGel); the test defect in the right parietal bone was filled with BCP
      (Straumann BoneCeramic) and covered with the same membrane. After a healing
      period of 2 months, the animals were sacrificed, and the samples were processed
      for histologic and histomorphometric analysis. RESULTS: The test defects
      regenerated with BCP and covered with the PEG membrane had a percentage of new
      bone formation area of 61.7% +/- 14.6%, and the control defects obtained mean new
      bone area of 57.3% +/- 21.8%. The difference between groups was not statistically
      significant. The BCP did not reveal osteoconductive properties, and few particles
      were fully incorporated into the newly formed bone. The BCP maintained the space,
      and there was extremely low particle resorption during the healing period. The
      PEG membrane remained intact. CONCLUSION: There were no statistically significant
      differences between the test and control groups. BCP did not exhibit
      osteoconductive properties.

PMID- 25397796
TI  - Parameters determining micromotion at the implant-abutment interface.
AB  - PURPOSE: Micromotion at the implant-abutment level has been reported to be a
      major determinant of longterm implant success, as technical problems ranging from
      screw loosening to screw fracture may occur as a consequence of excessive
      micromotion. MATERIALS AND METHODS: Following published standards, implant
      abutment assemblies were fixed in a universal testing machine at a 30-degree
      angle. A cyclic load of 200 N was applied to the specimens 10 times at a
      crosshead speed of 100 N/s while relative displacement between the implant and
      the abutment was quantified using extensometers. For five consecutive loading
      cycles per specimen, micromotion was recorded as a basis for statistical
      analysis, with two-sample t tests (Welch test) applied. RESULTS: Micromotion at
      the implant-abutment interface ranged from 1.52 to 94.00 MUm. While a significant
      effect of tightening torque was found, implant shoulder design did not reveal a
      significant effect in all cases. Lack of engagement of antirotational features of
      the implants resulted in increased micromotion. Casting onto prefabricated gold
      cylinders resulted in abutments with significantly less micromotion as compared
      to copy-milled and stock abutments. Computer-aided design/computer-assisted
      manufacture (CAD/CAM) zirconia abutments showed less micromotion than CAD/CAM
      titanium abutments. Inconsistent levels of micromotion were recorded for CAD/CAM
      abutments coupled to proprietary and competing implant systems. Great variations
      in micromotion were found with clone abutments and clone implant systems.
      CONCLUSION: A broad range of micromotion values was observed with the implant
      abutment combinations investigated. There seems to be no perfect implant shoulder
      geometry or perfect fabrication technique that would result in no detectable
      micromotion.

PMID- 25397797
TI  - Comparing pink and white esthetic scores to layperson perception in the single
      tooth implant patient.
AB  - PURPOSE: The pink esthetic score (PES) and white esthetic score (WES) are tools
      utilized to objectively evaluate single-tooth implant restorations (STIR) in the
      esthetic zone.1 A questionnaire study was developed to address two objectives:
      (1) establish a total PES/WES score that is clinically acceptable based on
      layperson perception and (2) report outcomes in laypeople's perceptions of pink
      and white deficiencies. MATERIALS AND METHODS: A presentation book of 27 color
      calibrated photographs of a STIR in the esthetic zone (canine to canine)
      surrounded by virgin teeth and one photograph without a STIR (control) was
      presented to three prosthodontists (evaluators) to conduct a PES/WES evaluation.
      The same 27 photographs were presented to 101 laypeople. The laypeople were
      instructed to identify which tooth was the STIR. The laypeople were also
      instructed to record, based on pink or white esthetics, what factors influenced
      their decision on the selection of the STIR. RESULTS: For the evaluator's scores
      of the 27 cases, the mean PES score was 5.7 (range, 3 to 10). The mean WES score
      was 6.2 (range, 3 to 10). The mean total PES/WES score was 11.9 (range, 6 to 20).
      The mean percentage of laypeople unable to correctly identify the STIR was 59.1%
      (range, 13.9% to 89.2%). When the evaluator's PES/WES score was greater than 12,
      79% of the layperson population was not able to identify a STIR (rho = -0.86). In
      addition, when the PES score was 6, 90% of the laypeople were not able to
      perceive a pink deficiency (rho = -0.65), and when the WES score was 6, 83% of
      the laypeople were not able to perceive a white deficiency (rho = -0.57).
      CONCLUSION: Within the limitations of this study, in single-tooth implant
      restorations, a total PES/WES score greater than 12 would provide a STIR that
      would be clinically acceptable in the majority of situations. This study also
      concluded that laypeople identify white esthetic deficiencies more easily than
      pink esthetic deficiencies.

PMID- 25397798
TI  - Alveolar ridge reconstruction with titanium mesh: a three-dimensional evaluation
      of factors affecting bone augmentation.
AB  - PURPOSE: To evaluate the three-dimensional (3D) reconstruction of atrophic
      alveolar ridges using titanium mesh (Ti-mesh) and its correlation with the extent
      and timing of mesh exposure and amount of reconstruction planned. MATERIALS AND
      METHODS: This study retrospectively evaluated 12 patients (mean age, 49.1 years)
      with 15 alveolar defects treated with Ti-mesh and particulate grafts (70/30
      autogenous bone/anorganic bovine bone) followed by implant placement 8 to 9
      months later. For each site, computed tomography images were analyzed using
      software designed to measure 3D volumes. The lacking bone volume (LBV) was
      calculated by subtracting the reconstructed bone volume at reentry from the
      planned bone volume (PBV). In all cases, the meshes were modeled preoperatively
      on a stereolithographic model. LBV was correlated with the extent and time of
      mesh exposure and PBV. RESULTS: The mean LBV (0.45 cm3) was 30.2% (range, 6% to
      74%) of the mean PBV (1.49 cm3). The mean extent and timing of mesh exposure,
      which occurred at 80% of augmented sites (12/15), were 0.73 cm2 (range, 0.09 to
      3.45 cm2) and 2.17 months (range, 1 to 8 months), respectively. LBV was
      significantly positively correlated with the area of mesh exposed, with 16.3% LBV
      for every cm2 of mesh exposed; there were positive correlations between LBV and
      early exposure and PBV. CONCLUSION: On average, there was 30.2% less bone than
      planned preoperatively; there was a significant negative correlation between the
      amount of reconstructed bone and area of mesh exposed.

PMID- 25397799
TI  - Clinical and radiographic evaluation of early loaded maxillary anterior single
      tooth bone-level implants.
AB  - PURPOSE: The aim of this study was to evaluate the clinical and radiographic
      outcomes of early loaded platform-switched implants in the anterior maxilla.
      MATERIALS AND METHODS: In this study, patients were treated with implants that
      supported all-ceramic single-tooth crowns and were followed for 2 to 4 years.
      Implants were evaluated on the basis of clinical and radiographic parameters,
      including Plaque Index, Sulcus Bleeding Index, peri-implant probing depths (PDs),
      Papilla Index, soft tissue recession, and marginal bone levels. Statistical
      analyses were performed. RESULTS: Fifty-five implants were placed in 47 patients.
      At the recall examinations, all implants had successfully integrated,
      demonstrating healthy peri-implant soft tissues as documented by standard
      clinical parameters. At the time of recall, 7 implants had been followed for 4
      years, 30 implants for 3 years, and 18 implants for 2 years. Plaque accumulation
      scores of 2 and 3 were not noted at any point during the study. At baseline, the
      mean PD was 2.1 +/- 0.6 mm, at 2 years it was 2.2 +/- 0.6 mm, at 3 years it was
      2.2 +/- 0.6 mm, and at 4 years (7 implants), the mean PD was 1.9 +/- 0.4 mm.
      There were no statistically significant differences between time intervals.
      Complete papilla fill was seen for 49 implants. All implants showed less than 0.5
      mm of marginal bone loss; mean bone loss at the time of final recall was 0.12 +/-
      0.22 mm. Seven implants showed an increase in the level of bone contact. There
      were no statistically significant differences over time. CONCLUSION: Bone-level
      implants with a platform-switched design are a successful treatment modality for
      anterior single-tooth implants.

PMID- 25397800
TI  - Influence of two different machined-collar heights on crestal bone loss.
AB  - PURPOSE: The purpose of this trial was to evaluate crestal bone level changes
      radiographically in a standardized fashion over a period of 12 months in humans
      for implants with a 0.7-mm machined collar (implant type A) versus type B
      implants with a 1.5-mm machined collar. MATERIALS AND METHODS: Twenty-five
      patients with multiple missing teeth in posterior sectors were randomly assigned
      to one of the two groups: A (0.7-mm machined-collar implants) or B (1.5-mm
      machined-collar implants). Changes at crestal bone level were assessed by
      measuring the shoulder-crest distance (SCD) on the mesial and distal aspects of
      each implant on customized periapical radiographs, which were taken on the day of
      surgery and 3, 6, and 12 months after surgery. RESULTS: Eighty-one implants were
      included in the study. Mean SCD was 0.54 +/- 0.53 mm at baseline and 1.49 +/-
      0.40 mm after 12 months. For 0.7-mm-collar implants, mean SCD was 1.40 +/- 0.39
      mm, while it was 1.56 +/- 0.40 mm for 1.5-mm-collar implants. Statistically
      significant differences were found only between the two types of implants for
      distal measurements at 3 and 12 months after placement. CONCLUSION: Both 0.7- and
      1.5-mm machined-collar implants can be used with predictable results, as changes
      in peri-implant crestal bone levels are similar for both implant types and do not
      seem to be significant from a clinical point of view. The SCD may well depend
      more on the location of the abutment-implant interface than on machined-collar
      height.

PMID- 25397801
TI  - Follow-up study of implants with turned or oxidized surfaces placed after sinus
      augmentation.
AB  - PURPOSE: To compare long-term survival and clinical outcomes of endosseous
      implants with different surface characteristics in patients with sinus elevation
      procedures, autologous bone grafting, and delayed implant placement. MATERIALS
      AND METHODS: Implant survival, peri-implant soft tissue conditions, marginal bone
      level, intrasinus apical bone level, and sinus health were studied in patients
      subjected to autologous bone graft and delayed placement of implants with turned
      or oxidized surfaces. After a minimum of 5 years of functional loading, all
      patients were clinically examined regarding gingival pocket depth (PD) and
      bleeding on probing (BoP). The marginal bone level (MBL) was measured in
      intraoral radiographs. Cone beam computed tomography was used to evaluate the
      apical bone level (ABL) of the implants and intrasinus conditions. RESULTS:
      Twenty-eight patients received sinus elevation and a total of 92 dental implants.
      Thirteen patients received 47 implants with a turned surface, and 15 patients
      received 45 implants with an oxidized surface. Mean follow-up was 10 years
      (range, 5 to 19 years). No significant difference was found between the two
      implant surfaces in terms of PD, BoP, MBL, or ABL. Four patients (14%) exhibited
      radiographic signs of sinus pathology, with opacification, polyp-like structures,
      and thickening of the sinus membrane. Radiographic signs of sinus pathology were
      not correlated to implant survival or to the investigated parameters. CONCLUSION:
      Grafting of the maxillary sinus floor with intraorally harvested bone and delayed
      placement of either turned or oxidized implants results in equally high long-term
      survival rates, stable marginal and apical bone levels, and good peri-implant
      soft tissue health.

PMID- 25397802
TI  - Early loading of mandibular implants placed immediately after extraction: a 10
      year prospective study of eight patients.
AB  - PURPOSE: This prospective study was undertaken to evaluate the 10-year implant
      survival rate as well as bone remodeling for immediately loaded anterior
      mandibular implants. MATERIALS AND METHODS: Patients with nonrestorable anterior
      mandibular teeth were enrolled. All mandibular teeth were extracted, and five
      rough-surfaced (titanium plasma spray) one-piece implants were placed, evenly
      spread between the mental foramina. All implants were immediately loaded with a
      provisional prosthesis. A definitive prosthesis was . RESULTS: Eight patients
      received 40 implants, 30 in extraction sockets and 10 in healed sites. All but
      two implants that did not achieve primary stability (35 Ncm) were immediately
      loaded. The progress of seven patients was evaluated after 10 years. The mean age
      at implant placement was 60 years, and the length of follow-up varied between
      10.3 and 11.47 years. The results showed a 100% implant retention rate; however,
      clinically observed bone loss around two central implants led to consideration
      for future surgical intervention or removal. Average bone loss was < 1 mm, and
      little difference was noted between implants placed in healed sites and those
      placed in extraction sockets. Technical problems with the prostheses were
      confined to two patients; one patient had seven fractures and the other had one.
      CONCLUSION: Rough-surfaced implants placed in extraction sockets between the
      mental foramina and immediately loaded can be successful in the long term.
      Because only is recommended that this site be avoided when immediately loaded
      implants are to be used in the anterior mandible.

PMID- 25397803
TI  - Immediate occlusal loading of full-arch rehabilitations: screw-retained versus
      cement-retained prosthesis. An 8-year clinical evaluation.
AB  - PURPOSE: The aim of this study was to evaluate the survival and success of screw
      retained versus cement-retained implant restorations in immediately loaded
      implants at 8-year follow-up. MATERIALS AND METHODS: Patients who were scheduled
      for full-arch ceramic prosthetic restorations were divided into two groups by
      randomization: in one group, prosthetic frameworks were screwed onto implants
      (screw-retained group, SRG), and in the second group, the frameworks were
      cemented on abutments (cement-retained group, CRG). Dental implants were placed
      both in postextraction and in healed sites. A temporary full-arch prosthesis was
      placed immediately after implant placement. Intraoral digital radiographic
      examinations (evaluating marginal bone levels) were made at baseline, 6 months,
      and each year after implant placement. RESULTS: In 28 patients, 24 full arches
      and 192 implants were placed in the maxilla and 10 full arches and 80 implants in
      the mandible (17 rehabilitations in each group). After an 8-year follow-up
      period, a survival rate of 99.27% was reported for all implants. Within the first
      year after implant placement, bone loss was recorded as follows: the CRG showed
      mean bone levels of -1.23 +/- 0.45 mm, while the SRG showed mean bone levels of 
      1.01 +/- 0.33 mm. After a 3-year follow-up, a slight increase was found (0.30 +/-
      0.25 mm in CRG and 0.45 +/- 0.29 mm in SRG). After that point, marginal bone
      levels remained stable over time, up to the 8-year follow-up. No statistically
      significant differences were found between groups (P > .05). CONCLUSION:
      Definitive cement- and screw-retained ceramic restorations are highly
      predictable, biocompatible, and esthetically pleasing, and the two groups
      presented no statistically significant differences in bone loss.

PMID- 25397804
TI  - A retrospective radiographic study on the effect of natural tooth-implant
      proximity and an introduction to the concept of a bone-loading platform switch.
AB  - PURPOSE: The aim of this study was to evaluate the effect of tooth-implant
      proximity using an implant system with a double platform shift that was designed
      to load bone coronal to the implant-abutment cohort study was conducted between
      January 2008 and December 2009. The sample was composed of patients who had
      received at least one 5-mm-wide hydroxyapatite-coated single-tooth Bicon implant
      that had been placed adjacent to at least one natural tooth. Descriptive
      statistics and univariate and multivariate linear mixed-effects regression
      models, adjusted for multiple implants in the same patient, were utilized. The
      primary predictor variable was the horizontal distance between implant and
      adjacent tooth, and the primary outcome variable was the change in peri-implant
      bone levels over time. RESULTS: Two hundred six subjects who received 235 plateau
      root-form implants were followed for an average of 42 months. Tooth-implant
      distance ranged between 0 and 14.6 mm. Out of 235 implants, 43 implants were
      placed < 1 mm to an adjacent natural tooth on mesial and/or distal sides. The
      proximity of a plateau root-form implant was not associated with complications on
      the adjacent tooth such as bone loss, root resorption, endodontic treatment,
      pain, or extraction. The proximity of an adjacent tooth was not a risk factor for
      the failure of a plateau root-form implant. After adjusting for other covariates
      in a multivariate model, the proximity of a natural tooth did not have a
      statistically significant effect on peri-implant bone levels (P = .13). The
      extraction of an adjacent tooth was associated with a significant increase in
      peri-implant bone loss (P = .008). CONCLUSION: The placement of a plateau root
      form implant with a sloping shoulder in close proximity to an adjacent tooth did
      not cause damage to that tooth or lead to bone loss or the failure of the
      implant.

PMID- 25397805
TI  - Implant survival rate and marginal bone loss of 6-mm short implants: a 2-year
      clinical report.
AB  - PURPOSE: This study aimed to evaluate (1) the association between implant
      diameter and marginal bone loss (MBL) of short (6 mm) implants and (2) the
      survival rates of short implants. MATERIALS AND METHODS: Thirty-three 6-mm
      implants were placed in the mandibles of 16 qualified patients. The selected
      sites had > 5 mm ridge width and < 9 mm bone height. None of the implant sites
      required bone augmentation procedures. All implants were uncovered 3 months after
      placement, and all patients were rehabilitated with 2- or 3-unit implant
      supported fixed partial dentures. Standardized periapical films were taken after
      24 months of function. Radiographs were digitalized, and MBL was assessed.
      RESULTS: For all implants, the mean MBL was 0.17 mm at the point of uncovering.
      At the 2-year follow-up, all implants were immobile and functional. Implants with
      4.2-mm diameters had significantly more MBL (1.95 mm) than wider implants (0.47
      mm and 0.35 mm for 5.0-mm and 6.0-mm implants, respectively). CONCLUSION: This 2
      year study illustrated that short implants are a viable option in selected
      clinical scenarios. Short implants with wider diameters are preferred because
      they have less marginal implant bone loss.

PMID- 25397806
TI  - Body fat indices and biomarkers of inflammation: a cross-sectional study with
      implications for obesity and peri-implant oral health.
AB  - PURPOSE: To examine the relationships between three measures of body fat-body
      mass index (BMI), waist circumference (WC), and total body fat percent-and
      markers of inflammation around dental implants in stable periodontal maintenance
      patients. MATERIALS AND METHODS: Seventy-three subjects were enrolled in this
      cross-sectional assessment. The study visit consisted of a physical examination
      that included anthropologic measurements of body composition (BMI, WC, body fat
      %); intraoral assessments were performed (full-mouth plaque index, periodontal
      and peri-implant comprehensive examinations) and peri-implant sulcular fluid
      (PISF) was collected on the study implants. Levels of interleukin (IL)-1alpha, IL
      1beta, IL-6, IL-8, IL-10, IL-12, IL-17, tumor necrosis factor-alpha, C-reactive
      protein, osteoprotegerin, leptin, and adiponectin in the PISF were measured using
      multiplex proteomic immunoassays. Correlation analysis with body fat measures was
      then performed using appropriate statistical methods. RESULTS: After adjustments
      for covariates, regression analyses revealed statistically significant
      correlation between IL-1beta in PISF and WC (R = 0.33; P = .0047). CONCLUSION: In
      this study in stable periodontal maintenance patients, a modest but statistically
      significant positive correlation was observed between the levels of IL-1beta, a
      major proinflammatory cytokine in PISF, and WC, a reliable measure of central
      obesity.

PMID- 25397808
TI  - Osteoblast response to titanium surfaces coated with strontium ranelate-loaded
      chitosan film.
AB  - PURPOSE: Improving the peri-implant bone quality has notable clinical value in
      cases of osteoporosis following implant insertion. MATERIALS AND METHODS: In this
      study, strontium ranelate-loaded chitosan film was produced on a titanium surface
      in different concentrations of strontium ranelate (SR) (0, 2, 20, 40, and 80
      mmol/L of the strontium ion [Sr2+]) with the expectation of utilizing the bone
      healing-enhancement effect of Sr2+. The physicochemical properties of SR-loaded
      chitosan films were characterized by x-ray diffraction (XRD), scanning electron
      microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The
      release/dissolution mechanism was tested by inductively coupled plasma optical
      emission spectrometry (ICP-OES), and in vitro cell responses were evaluated using
      primary osteoblasts (POBs) in terms of cell proliferation, alkaline phosphatase
      (ALP) activity, and quantitative analysis of key osteoblastic gene expression.
      RESULTS: XRD and FTIR observation showed that only a few SRs reacted chemically
      with chitosan through hydrogen bonds or conjugate action. The initial burst
      release (70% to 85%) of Sr2+ occurred in the first 3 days and was followed by a
      slower release stage. At a low concentration (2 mmol/L or 20 mmol/L), SR-loaded
      chitosan film promoted cell responses of POBs with enhanced proliferation, ALP
      activity, and expression levels of bone morphogenetic protein 2 (BMP-2), runt
      related transcription factor 2 (Runx-2), ALP, and osteocalcin, but at a high
      concentration (40 mmol/L or 80 mmol/L), it inhibited POB growth. CONCLUSION:
      These results indicated that SR-loaded chitosan film on a titanium surface
      promotes osteoblast proliferation and differentiation in a dose-dependent manner,
      which may represent a new approach in the treatment of a titanium implant.

PMID- 25397807
TI  - Comparing variable-length polyglutamate domains to anchor an osteoinductive
      collagen-mimetic peptide to diverse bone grafting materials.
AB  - PURPOSE: Allografts, xenografts, and alloplasts are commonly used in craniofacial
      medicine as alternatives to autogenous bone grafts; however, these materials lack
      important bone-inducing proteins. A method for enhancing the osteoinductive
      potential of these commercially available materials would provide a major
      clinical advance. In this study, a calcium-binding domain, polyglutamate, was
      added to an osteoinductive peptide derived from collagen type I, Asp-Gly-Glu-Ala
      (DGEA), to anchor the peptide onto four different materials: freeze-dried bone
      allograft (FDBA); anorganic bovine bone (ABB); beta-tricalcium phosphate (beta
      TCP); and a calcium sulfate bone cement (CaSO4). The authors also examined
      whether peptide binding and retention could be tuned by altering the number of
      glutamate residues within the polyglutamate domain. MATERIALS AND METHODS: DGEA
      or DGEA modified with diglutamate (E2DGEA), tetraglutamate (E4DGEA), or
      heptaglutamate (E7DGEA) were evaluated for binding and release to the grafting
      materials. Peptides were conjugated with a fluorescein isothiocyanate (FITC) tag
      to allow monitoring by fluorescent microscopy or through measurements of solution
      fluorescence. In vivo retention was evaluated by implanting graft materials
      coated with FITC-peptides into rat subcutaneous pouches. RESULTS: Significantly
      more peptide was loaded onto the four graft materials as the number of glutamates
      increased, with E7DGEA exhibiting the greatest binding. There was also
      significantly greater retention of peptides with longer glutamate domains
      following a 3-day incubation with agitation. Importantly, E7DGEA peptides
      remained on the grafts after a 2-month implantation into skin pouches, a
      sufficient interval to influence bony healing. CONCLUSION: Variable-length
      polyglutamate domains can be added to osteoinductive peptides to control the
      amount of peptide bound and rate of peptide released. The lack of methods for
      tunable coupling of biologics to commercial graft sources has been a major
      barrier toward developing materials that approach the clinical efficacy of
      autogenous bone. Modification of osteoinductive factors with polyglutamate
      domains constitutes a technically straightforward and cost-effective strategy for
      enhancing osteoinductivity of diverse graft products.

PMID- 25397809
TI  - Biomechanical factors associated with mandibular cantilevers: analysis with three
      dimensional finite element models.
AB  - PURPOSE: Although the risks of using a cantilever to treat missing teeth have
      been described, the mechanisms remain unclear. This study aimed to reveal these
      mechanisms from a biomechanical perspective. The effects of various implant
      sites, number of implants, and superstructural connections on stress distribution
      in the marginal bone were analyzed with three-dimensional finite element models
      based on mandibular computed tomography data. Forces from the masseter,
      temporalis, and internal pterygoid were applied as vectors. MATERIALS AND
      METHODS: Two three-dimensional finite element models were created with the
      edentulous mandible showing severe and relatively modest residual ridge
      resorption. Cantilevers of the premolar and molar were simulated in the
      superstructures in the models. The following conditions were also included as
      factors in the models to investigate changes: poor bone quality, shortened dental
      arch, posterior occlusion, lateral occlusion, double force of the masseter, and
      short implant. Multiple linear regression analysis with a forced-entry method was
      performed with stress values as the objective variable and the factors as the
      explanatory variable. RESULTS: When bone mass was high, stress around the implant
      caused by differences in implantation sites was reduced. When bone mass was low,
      the presence of a cantilever was a possible risk factor. The stress around the
      implant increased significantly if bone quality was poor or if increased force
      (eg, bruxism) was applied. CONCLUSION: The addition of a cantilever to the
      superstructure increased stress around implants. When large muscle forces were
      applied to a superstructure with cantilevers or if bone quality was poor, stress
      around the implants increased.

PMID- 25397812
TI  - Adaptive firefly algorithm: parameter analysis and its application.
AB  - As a nature-inspired search algorithm, firefly algorithm (FA) has several control
      parameters, which may have great effects on its performance. In this study, we
      investigate the parameter selection and adaptation strategies in a modified
      firefly algorithm - adaptive firefly algorithm (AdaFa). There are three
      strategies in AdaFa including (1) a distance-based light absorption coefficient;
      (2) a gray coefficient enhancing fireflies to share difference information from
      attractive ones efficiently; and (3) five different dynamic strategies for the
      randomization parameter. Promising selections of parameters in the strategies are
      analyzed to guarantee the efficient performance of AdaFa. AdaFa is validated over
      widely used benchmark functions, and the numerical experiments and statistical
      tests yield useful conclusions on the strategies and the parameter selections
      affecting the performance of AdaFa. When applied to the real-world problem -
      protein tertiary structure prediction, the results demonstrated improved variants
      can rebuild the tertiary structure with the average root mean square deviation
      less than 0.4A and 1.5A from the native constrains with noise free and 10%
      Gaussian white noise. 

PMID- 25397810
TI  - Analysis of the Na+/Ca2+ exchanger gene family within the phylum Nematoda.
AB  - Na+/Ca2+ exchangers are low affinity, high capacity transporters that rapidly
      transport calcium at the plasma membrane, mitochondrion, endoplasmic (and
      sarcoplasmic) reticulum, and the nucleus. Na+/Ca2+ exchangers are widely
      expressed in diverse cell types where they contribute homeostatic balance to
      calcium levels. In animals, Na+/Ca2+ exchangers are divided into three groups
      based upon stoichiometry: Na+/Ca2+ exchangers (NCX), Na+/Ca2+/K+ exchangers
      (NCKX), and Ca2+/Cation exchangers (CCX). In mammals there are three NCX genes,
      five NCKX genes and one CCX (NCLX) gene. The genome of the nematode
      Caenorhabditis elegans contains ten Na+/Ca2+ exchanger genes: three NCX; five
      CCX; and two NCKX genes. Here we set out to characterize structural and taxonomic
      specializations within the family of Na+/Ca2+ exchangers across the phylum
      Nematoda. In this analysis we identify Na+/Ca2+ exchanger genes from twelve
      species of nematodes and reconstruct their phylogenetic and evolutionary
      relationships. The most notable feature of the resulting phylogenies was the
      heterogeneous evolution observed within exchanger subtypes. Specifically, in the
      case of the CCX exchangers we did not detect members of this class in three Clade
      III nematodes. Within the Caenorhabditis and Pristionchus lineages we identify
      between three and five CCX representatives, whereas in other Clade V and also
      Clade IV nematode taxa we only observed a single CCX gene in each species, and in
      the Clade III nematode taxa that we sampled we identify NCX and NCKX encoding
      genes but no evidence of CCX representatives using our mining approach. We also
      provided re-annotation for predicted CCX gene structures from Heterorhabditis
      bacteriophora and Caenorhabditis japonica by RT-PCR and sequencing. Together,
      these findings reveal a complex picture of Na+/Ca2+ transporters in nematodes
      that suggest an incongruent evolutionary history of proteins that provide central
      control of calcium dynamics.

PMID- 25397813
TI  - Effect of nitrogen source concentration on curdlan production by Agrobacterium
      sp. ATCC 31749 grown on prairie cordgrass hydrolysates.
AB  - The effect of nitrogen source concentration on the production of the
      polysaccharide curdlan by the bacterium Agrobacterium sp. ATCC 31749 from
      hydrolysates of prairie cordgrass was examined. The highest curdlan
      concentrations were produced by ATCC 31749 when grown on a medium containing a
      solids-only hydrolysate and the nitrogen source ammonium phosphate (2.2 mM) or on
      a medium containing a complete hydrolysate and 3.3 mM ammonium phosphate. The
      latter medium sustained a higher level of bacterial curdlan production than the
      former medium after 144 hr. Biomass production by ATCC 31749 was highest after
      144 hr when grown on a medium containing a solids-only hydrolysate and 2.2 or 8.7
      mM ammonium phosphate. On the medium containing the complete hydrolysate, biomass
      production by ATCC 31749 was highest after 144 hr when 3.3 mM ammonium phosphate
      was present. Bacterial biomass production after 144 hr was greater on the
      complete hydrolysate medium compared to the solids-only hydrolysate medium.
      Curdlan yield produced by ATCC 31749 after 144 hr from the complete hydrolysate
      medium containing 3.3 mM ammonium phosphate was higher than from the solids-only
      hydrolysate medium containing 2.2 mM ammonium phosphate.

PMID- 25397814
TI  - Inhabiting the sexual landscape: toward an interpretive theory of the development
      of sexual orientation and identity.
AB  - Building on Paula Rust's (1996) concept of a sexual landscape, we propose an
      interpretive theory of the development of both sexual orientation and sexual
      identity. We seek to reconcile human agency with active and shifting influences
      in social context and to recognize the inherent complexity of environmental
      factors while acknowledging the role that biological potential plays. We ground
      our model in the insights of three compatible and related theoretical
      perspectives: social constructionism, symbolic interactionism, and scripting
      theory. Within this framework, we explain how sexual orientation and sexual
      identities develop and potentially change.

PMID- 25397816
TI  - Complementary and alternative medicine for US veterans and active duty military
      personnel: promising steps to improve their health.

PMID- 25397817
TI  - Mindful attention increases and mediates psychological outcomes following mantram
      repetition practice in veterans with posttraumatic stress disorder.
AB  - BACKGROUND: Several evidence-based treatments are available to veterans diagnosed
      with posttraumatic stress disorder (PTSD). However, not all veterans benefit from
      these treatments or prefer to engage in them. OBJECTIVES: The current study
      explored whether (1) a mantram repetition program (MRP) increased mindful
      attention among veterans with PTSD, (2) mindful attention mediated reduced PTSD
      symptom severity and enhanced psychological well-being, and (3) improvement in
      mindful attention was due to the frequency of mantram repetition practice.
      RESEARCH DESIGN: Data from a randomized controlled trial comparing MRP plus
      treatment as usual (MRP+TAU) or TAU were analyzed using hierarchical linear
      models. SUBJECTS: A total of 146 veterans with PTSD from military-related trauma
      were recruited from a Veterans Affairs outpatient PTSD clinic (71 MRP+TAU; 75
      TAU). MEASURES: The Clinician Administered PTSD Scale (CAPS), PTSD Checklist
      (PCL), the Brief Symptom Inventory-18 depression subscale, Health Survey SF-12v2,
      and Mindfulness Attention Awareness Scale (MAAS) were used. Frequency of mantram
      repetition practice was measured using wrist-worn counters and daily logs.
      RESULTS: Intent-to-treat analyses indicated greater increases in mindful
      attention, as measured by the MAAS, for MRP+TAU as compared with TAU participants
      (P<0.01). Mindful attention gains mediated previously reported treatment effects
      on reduced PTSD symptoms (using both CAPS and PCL), reduced depression, and
      improved psychological well-being. Frequency of mantram repetition practice in
      turn mediated increased mindful attention. CONCLUSIONS: The MRP intervention and
      specifically, mantram practice, improved mindful attention in veterans with PTSD,
      yielding improved overall psychological well-being. MRP may be a beneficial
      adjunct to usual care in veterans with PTSD.

PMID- 25397818
TI  - Mindfulness-based stress reduction (MBSR) reduces anxiety, depression, and
      suicidal ideation in veterans.
AB  - INTRODUCTION: Anxiety, depression, and pain are major problems among veterans,
      despite the availability of standard medical options within the Veterans Health
      Administration. Complementary and alternative approaches for these symptoms have
      been shown to be appealing to veterans. One such complementary and alternative
      approach is mindfulness-based stress reduction (MBSR), a brief course that
      teaches mindfulness meditation with demonstrated benefits for mood disorders and
      pain. METHODS: We prospectively collected data on MBSR's effectiveness among 79
      veterans at an urban Veterans Health Administration medical facility. The MBSR
      course had 9 weekly sessions that included seated and walking meditations, gentle
      yoga, body scans, and discussions of pain, stress, and mindfulness. Pre-MBSR and
      post-MBSR questionnaires investigating pain, anxiety, depression, suicidal
      ideation, and physical and mental health functioning were obtained and compared
      for individuals. We also conducted a mediation analysis to determine whether
      changes in mindfulness were related to changes in the other outcomes. RESULTS:
      Significant reductions in anxiety, depression, and suicidal ideation were
      observed after MBSR training. Mental health functioning scores were improved.
      Also, mindfulness interacted with other outcomes such that increases in
      mindfulness were related to improvements in anxiety, depression, and mental
      health functionality. Pain intensity and physical health functionality did not
      show improvements. DISCUSSION: This naturalistic study in veterans shows that
      completing an MBSR program can improve symptoms of anxiety and depression, in
      addition to reducing suicidal ideations, all of which are of critical importance
      to the overall health of the patients.

PMID- 25397819
TI  - Reductions in cortisol associated with primary care brief mindfulness program for
      veterans with PTSD.
AB  - BACKGROUND: Patients with posttraumatic stress disorder (PTSD) have significant
      medical morbidity, which may be mediated by hypothalamic pituitary axis (HPA)
      dysfunction and reflected in cortisol output. Many veterans with PTSD are
      hesitant to engage in trauma-focused exposure treatments; therefore briefer, non
      exposure-based treatments are needed; one such promising approach is an
      abbreviated Primary Care brief Mindfulness Program (PCbMP). OBJECTIVE: This study
      investigated the relationship between dose-response to participation in a
      veterans PCbMP program and diurnal cortisol. Cortisol reflects HPA function and
      PTSD is associated with HPA dysregulation. RESEARCH DESIGN: Veterans with PTSD
      were identified in PC and randomly assigned to treatment as usual (TAU, n=21) or
      participation in brief 4-week Mindfulness Based Stress Reduction program (n=19).
      SUBJECTS: Veterans (n=40) (mean age, 48+/-16 y; 90% men) with PTSD referred
      through their VA PC provider and randomly assigned to PCbMP or TAU. MEASURE: As
      an objective indicator of HPA function, salivary diurnal cortisol was measured
      from samples collected across 2 consecutive days at baseline and follow-up.
      RESULTS: Analyses revealed that significant changes in cortisol were associated
      with PCbMP treatment engagement and dosing (number of mindfulness program
      sessions completed). Veterans completing 4 mindfulness-based meditation sessions
      significantly reduced their cortisol awakening response (P<=0.05); and had
      significant changes in cortisol area under the curve increase compared with TAU
      participants (P<=0.05). Results indicate that PCbMP has a beneficial
      physiological impact on veterans with PTSD with a minimum of 4 weeks of practice.

PMID- 25397820
TI  - Loving-kindness meditation and the broaden-and-build theory of positive emotions
      among veterans with posttraumatic stress disorder.
AB  - BACKGROUND: Loving-kindness meditation (LKM) is a practice intended to enhance
      feelings of kindness and compassion for self and others. OBJECTIVES: To assess
      whether participation in a 12-week course of LKM for veterans with posttraumatic
      stress disorder (PTSD) is associated with improved positive emotions,
      decentering, and personal resources. RESEARCH DESIGN: In an open-pilot trial,
      veterans were assessed at baseline, after the course, and 3 months later. Effect
      sizes were calculated from baseline to each follow-up point for each construct of
      interest. Measures were chosen as an initial investigation of the broaden-and
      build theory of positive emotions. SUBJECTS: A total of 42 veterans with active
      PTSD (40% female) participated. MEASURES: Emotions, decentering, psychological
      wellbeing including autonomy, environmental mastery, personal growth, positive
      relations, purpose in life, self-acceptance, and sense of social support were
      measured at each time point. RESULTS: Significant increases in unactivated
      pleasant (d=0.73), but not activated pleasant, emotions were found over time.
      Activated and unactivated unpleasant emotions decreased over time (d=-0.69 and 
      0.53, respectively). There were also increases in environmental mastery (d=0.61),
      personal growth (d=0.54), purpose in life (d=0.71), self-acceptance (d=0.68), and
      decentering (d=0.96) at 3-month follow-up. CONCLUSIONS: Overall, positive
      emotions increased, and enhancement of personal resources occurred over time.
      Further investigation of LKM for PTSD is warranted.

PMID- 25397821
TI  - Physical health, mental health, and utilization of complementary and alternative
      medicine services among Gulf War veterans.
AB  - BACKGROUND: Gulf War veterans represent a unique subset of the veteran
      population. It has been challenging to identify interventions that result in
      improvements in physical and mental health for this population. Recently, there
      has been recognition of a potential role for complementary and alternative
      medicine (CAM) interventions. OBJECTIVES: This paper examines the characteristics
      of Gulf War and non-Gulf War veterans referred to a CAM clinic, and explores the
      utilization of services by this population. METHOD AND SUBJECTS: Participants
      included 226 veterans enrolled in a CAM clinic at a Veterans Affairs medical
      center, 42 of whom were Gulf War veterans. Self-report measures of
      physical/mental health were administered, and service utilization was obtained
      from participants' medical records for a 6-month period. RESULTS: Gulf War
      veterans enrolled in the program reported more severe physical and mental health
      symptoms than non-Gulf War veterans. However, examining only veterans who
      participated in services in the 6 months following enrollment, the 2 groups
      reported similar symptom severity. Both groups were similar in their attendance
      of individual acupuncture and iRest yoga nidra, although Gulf War veterans
      attended fewer sessions of group acupuncture. CONCLUSIONS: Although Gulf War
      veterans who enroll in a CAM program may have more severe symptoms than non-Gulf
      War veterans, those who actually participate in services are similar to non-Gulf
      War veterans on these measures. These groups also differ in their pattern of
      service utilization. Future research should explore the reasons for these
      differences, and to identify ways to promote treatment engagement with this
      population.

PMID- 25397822
TI  - CAM utilization among OEF/OIF veterans: findings from the National Health Study
      for a New Generation of US Veterans.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is increasingly seen as
      an adjunct to traditional plans of care. This study utilized a representative
      sample of Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF)
      veterans and OEF/OIF-era veterans to explore the prevalence and characteristics
      of CAM users. RESEARCH DESIGN: The National Health Study for a New Generation of
      US Veterans (NewGen) is a longitudinal health study of a population-based cohort
      of OEF/OIF (deployed) and OEF/OIF-era (nondeployed) veterans. Data from the 2009
      2011 NewGen survey (n=20,563) were analyzed to determine prevalence of CAM use by
      demographic and military characteristics, the types of CAM modalities used, and
      where the modalities were sought. Results were weighted to the entire population
      of OEF/OIF and OEF/OIF-era veterans. RESULTS: There was no statistically
      significant association between CAM use and deployment. Those who used Department
      of Veterans Affairs (VA) health care after separation were more likely to be CAM
      users compared with those who did not use VA care; however, the majority of
      veterans using CAM are using it outside the VA health care system. Massage was
      the most prevalent CAM modality followed by chiropractic treatment; males were
      less likely to use CAM than women. CONCLUSIONS: CAM modalities are being utilized
      by OEF/OIF veterans for health problems mainly outside the VA. Policymakers
      should determine appropriate use of these modalities.

PMID- 25397823
TI  - Whole health: the vision and implementation of personalized, proactive, patient
      driven health care for veterans.

PMID- 25397824
TI  - A factor analysis and exploration of attitudes and beliefs toward complementary
      and conventional medicine in veterans.
AB  - BACKGROUND: Although Veterans utilize complementary and alternative medicine
      (CAM) at rates comparable with civilians, little is known about Veterans'
      attitudes and beliefs toward CAM. Measures to increase such knowledge may help to
      identify treatment preferences, particularly among those with signature
      conditions from the recent conflicts [ie, traumatic brain injury (TBI),
      posttraumatic stress disorder (PTSD)]. OBJECTIVE: This exploratory study aimed
      to: (1) determine the factors of the Complementary, Alternative, and Conventional
      Medicine Attitudes Scale (CACMAS); and to utilize the resulting factors to
      describe (2) attitudes and beliefs toward CAM; (3) their association with TBI,
      PTSD, and history of self-directed violence. Patterns of CAM use were also
      obtained. RESEARCH DESIGN: Factor analysis. Observational study. SUBJECTS:
      Participants were 97 Veterans seeking care at a Mountain State Veterans Affairs
      Medical Center. METHODS: Participants completed the CACMAS, clinical interviews,
      and self-report measures during a single visit. RESULTS: CACMAS factors
      identified were: acceptability of (1) CAM and (2) conventional medicine; (3) mind
      body integration; and (4) belief in CAM. Acceptability of CAM was significantly
      associated with history of mild TBI (mTBI) or PTSD symptom severity. Veterans
      endorsed a wide range of CAM use. CONCLUSIONS: Veterans in this sample were open
      to CAM and conventional medicine, believed in CAM, and believed that treatments
      should incorporate the mind and body. Veterans with a history of mTBI or PTSD
      symptoms may be more accepting of CAM. Understanding Veterans' beliefs and
      attitudes regarding CAM may help providers deliver patient-centered treatments,
      particularly among those with conditions for which evidence-based interventions
      are limited (eg, mTBI).

PMID- 25397825
TI  - Randomized effectiveness trial of a brief course of acupuncture for posttraumatic
      stress disorder.
AB  - BACKGROUND: Initial posttraumatic stress disorder (PTSD) care is often delayed
      and many with PTSD go untreated. Acupuncture appears to be a safe, potentially
      nonstigmatizing treatment that reduces symptoms of anxiety, depression, and
      chronic pain, but little is known about its effect on PTSD. METHODS: Fifty-five
      service members meeting research diagnostic criteria for PTSD were randomized to
      usual PTSD care (UPC) plus eight 60-minute sessions of acupuncture conducted
      twice weekly or to UPC alone. Outcomes were assessed at baseline and 4, 8, and 12
      weeks postrandomization. The primary study outcomes were difference in PTSD
      symptom improvement on the PTSD Checklist (PCL) and the Clinician-administered
      PTSD Scale (CAPS) from baseline to 12-week follow-up between the 2 treatment
      groups. Secondary outcomes were depression, pain severity, and mental and
      physical health functioning. Mixed model regression and t test analyses were
      applied to the data. RESULTS: Mean improvement in PTSD severity was significantly
      greater among those receiving acupuncture than in those receiving UPC
      (PCLDelta=19.8+/-13.3 vs. 9.7+/-12.9, P<0.001; CAPSDelta=35.0+/-20.26 vs. 10.9+/
      20.8, P<0.0001). Acupuncture was also associated with significantly greater
      improvements in depression, pain, and physical and mental health functioning. Pre
      post effect-sizes for these outcomes were large and robust. CONCLUSIONS:
      Acupuncture was effective for reducing PTSD symptoms. Limitations included small
      sample size and inability to parse specific treatment mechanisms. Larger
      multisite trials with longer follow-up, comparisons to standard PTSD treatments,
      and assessments of treatment acceptability are needed. Acupuncture is a novel
      therapeutic option that may help to improve population reach of PTSD treatment.

PMID- 25397826
TI  - US veterans use vitamins and supplements as substitutes for prescription
      medication.
AB  - BACKGROUND: Vitamins and supplements are the most commonly used form of
      complementary and alternative medicine in the United States. Growing research
      suggests that patients substitute vitamins and supplements for their prescription
      medications. The reasons might include cost of prescription medications and
      discordant patient and doctor health belief systems. OBJECTIVES: To investigate
      the prevalence of substitution of vitamins and supplements for prescription
      medications among veterans who receive care in the VA health care system and
      whether substitution is associated with prescription rationing due to cost,
      treatment beliefs, or distrust of the health system. RESEARCH DESIGN: Cross
      sectional observational survey. SUBJECTS: Primary care patients (n=275) at the
      Philadelphia VA Medical Center. MEASURES: Medication substitution, prescription
      medication rationing, treatment beliefs, and health system distrust were measured
      with structured instruments. Multivariate logistic regression was performed with
      substitution as the dependent variable. RESULTS: A significant number of primary
      care patients in the VA system use vitamins and supplements 206 (75%). The
      prevalence of medication substitution is high 48 (18%). Medication substitution
      is strongly associated with prescription rationing due to cost (adjusted odds
      ratio 6.3, 95% confidence interval: 2.0-19.5, P=0.001). Similarly, greater belief
      in complementary and alternative approaches to care positively predicts
      medication substitution (adjusted odds ratio 1.08, 95% confidence interval: 1.01
      1.15, P=0.011). There is no significant association between health system
      distrust and likelihood of medication substitution. CONCLUSIONS: Medication
      substitution is prevalent in this sample of inner city primary care patients who
      receive care in the VA system. Cost of prescriptions and belief in the value of
      complementary and alternative approaches to care appear to be associated with
      this patient-driven treatment decision.

PMID- 25397827
TI  - A systematic scoping review of complementary and alternative medicine mind and
      body practices to improve the health of veterans and military personnel.
AB  - BACKGROUND: Meditation, imagery, acupuncture, and yoga are the most frequently
      offered mind and body practices in the Department of Veterans Affairs. Yet, the
      research on mind and body practices has been critiqued as being too limited in
      evidence and scope to inform clinical treatment. OBJECTIVES: We conducted a
      systematic scoping review of mind and body practices used with veterans or active
      duty military personnel to identify gaps in the literature and make
      recommendations for future primary research. RESEARCH DESIGN: Following
      systematic literature review methodology, we searched 5 databases using 27
      different National Center for Complementary and Alternative Medicine-defined mind
      and body practices as text words, keywords, and MeSH terms through June 30, 2014.
      We also conducted handsearches of 4 previous reviews. SUBJECTS: Active duty
      military members or veterans 18 years or older participating in mind and body
      practice interventions globally. MEASURES: Data were extracted from studies
      meeting 5 inclusion criteria. The quality of randomized controlled trials (RCTs)
      was assessed using an existing checklist. RESULTS: Of 1819 studies identified, 89
      interventions (50 RCTs) published between 1976 and 2014, conducted in 9
      countries, using 152 different measures to assess 65 health and well-being
      outcomes met our inclusion criteria. Most interventions took place in the United
      States (n=78). Meditation practices (n=25), relaxation techniques including
      imagery (n=20), spinal manipulation including physical therapy (n=16), and
      acupuncture (n=11) were the most frequently studied practices. Methodological
      quality of most RCTs was rated poorly. CONCLUSIONS: Meditation and acupuncture
      practices are among the most frequently offered and studied mind and body
      practices. Future research should include yoga as it is currently understudied
      among veterans and military personnel. A repository of mind and body intervention
      outcome measures may further future research efforts, as would conducting
      pragmatic trials and more robust RCTs.

PMID- 25397828
TI  - Complementary and alternative medicine among veterans and military personnel: a
      synthesis of population surveys.
AB  - BACKGROUND: Recent reports reinforce the widespread interest in complementary and
      alternative medicine (CAM), not only among military personnel with combat-related
      disorders, but also among providers who are pressed to respond to patient demand
      for these therapies. However, an understanding of utilization of CAM therapies in
      this population is lacking. OBJECTIVE: The goals of this study are to synthesize
      the content of self-report population surveys with information on use of CAM in
      military and veteran populations, assess gaps in knowledge, and suggest ways to
      address current limitations. RESEARCH DESIGN: The research team conducted a
      literature review of population surveys to identify CAM definitions, whether
      military status was queried, the medical and psychological conditions queried,
      and each specific CAM question. Utilization estimates specific to
      military/veterans were summarized and limitations to knowledge was classified.
      RESULTS: Seven surveys of CAM utilization were conducted with military/veteran
      groups. In addition, 7 household surveys queried military status, although there
      was no military/veteran subgroup analysis. Definition of CAM varied widely
      limiting cross-survey analysis. Among active duty and Reserve military, CAM use
      ranged between 37% and 46%. Survey estimates do not specify CAM use that is
      associated with a medical or behavioral health condition. CONCLUSIONS:
      Comparisons between surveys are hampered due to variation in methodologies. Too
      little is known about reasons for using CAM and conditions for which it is used.
      Additional information could be drawn from current surveys with additional
      subgroup analysis, and future surveys of CAM should include military status
      variable.

PMID- 25397829
TI  - CAM in the United States military: too little of a good thing?

PMID- 25397830
TI  - Perceptions of providers and administrators in the Veterans Health Administration
      regarding complementary and alternative medicine.
AB  - BACKGROUND: The integration of complementary and alternative medicine (CAM)
      therapies into a large organization such as the Veterans Health Administration
      (VHA) requires cultural change and deliberate planning to ensure feasibility and
      buy-in from staff and patients. At present, there is limited knowledge of VHA
      patient care providers' and administrators' viewpoints regarding CAM therapies
      and their implementation. OBJECTIVES: Our purpose was to qualitatively examine
      knowledge, attitudes, perceived value and perceived barriers, and/or facilitators
      to CAM program implementation among VHA providers and administrators at a large
      VHA facility. RESEARCH DESIGN: We are reporting the qualitative interview portion
      of a mixed-methods study. SUBJECTS: Twenty-eight participants (patient care
      providers or administrators) were purposely chosen to represent a spectrum of
      positions and services. Participants' experience with and exposure to CAM
      therapies varied. MEASURES: Individual interviews were conducted using a semi
      structured format and were digitally recorded, transcribed, and coded for themes.
      RESULTS: Recurrent themes included: a range of knowledge about CAM; benefits for
      patients and staff; and factors that can be facilitators or barriers including
      evidence-based practice or perceived lack thereof, prevailing culture, leadership
      at all levels, and lack of position descriptions for CAM therapists. Participants
      rated massage, meditation, acupuncture, and yoga as priorities for promotion
      across the VHA. CONCLUSIONS: Despite perceived challenges, providers and
      administrators recognized the value of CAM and potential for expansion of CAM
      within the VHA. Interview results could inform the process of incorporating CAM
      into a plan for meeting VHA Strategic Goal One of personalized, proactive,
      patient-driven health care across the VHA.

PMID- 25397832
TI  - The british association of sport and exercise sciences expert statements.

PMID- 25397833
TI  - Day 1. Free communications - physiology and nutrition.

PMID- 25397831
TI  - Variations in the implementation and characteristics of chiropractic services in
      VA.
AB  - BACKGROUND: In 2004, the US Department of Veterans Affairs expanded its delivery
      of chiropractic care by establishing onsite chiropractic clinics at select
      facilities across the country. Systematic information regarding the planning and
      implementation of these clinics and describing their features and performance is
      lacking. OBJECTIVES: To document the planning, implementation, key features and
      performance of VA chiropractic clinics, and to identify variations and their
      underlying causes and key consequences as well as their implications for policy,
      practice, and research on the introduction of new clinical services into
      integrated health care delivery systems. RESEARCH DESIGN, METHODS, AND SUBJECTS:
      Comparative case study of 7 clinics involving site visit-based and telephone
      based interviews with 118 key stakeholders, including VA clinicians, clinical
      leaders and administrative staff, and selected external stakeholders, as well as
      reviews of key documents and administrative data on clinic performance and
      service delivery. Interviews were recorded, transcribed, and analyzed using a
      mixed inductive (exploratory) and deductive approach. RESULTS AND CONCLUSIONS:
      Interview data revealed considerable variations in clinic planning and
      implementation processes and clinic features, as well as perceptions of clinic
      performance and quality. Administrative data showed high variation in patterns of
      clinic patient care volume over time. A facility's initial willingness to
      establish a chiropractic clinic, along with a higher degree of perceived evidence
      based and collegial attributes of the facility chiropractor, emerged as key
      factors associated with higher and more consistent delivery of chiropractic
      services and higher perceived quality of those services.

PMID- 25397834
TI  - Day 1. Free communications - sport and performance.

PMID- 25397835
TI  - Day 1. Free communications - psychology (session 1).

PMID- 25397836
TI  - Day 1. Free communications - psychology (session 2).

PMID- 25397838
TI  - Day 1. Posters - biomechanics.

PMID- 25397837
TI  - Day 1. Free communications - biomechanics.

PMID- 25397839
TI  - Day 1. Posters - physical activity for health.

PMID- 25397841
TI  - Day 1. Posters - psychology.

PMID- 25397840
TI  - Day 1. Posters - physiology and nutrition.

PMID- 25397843
TI  - Day 2. Free communications - physical activity for health.

PMID- 25397842
TI  - Day 1. Posters - sport and performance.

PMID- 25397844
TI  - Day 2. Free communications - physiology and nutrition.

PMID- 25397845
TI  - Day 2. Free communications - sport and performance (session 1).

PMID- 25397846
TI  - Day 2. Free communications - sport and performance (session 2).

PMID- 25397847
TI  - Day 2. Free communications - psychology (session 1).

PMID- 25397848
TI  - Day 2. Free communications - psychology (session 2).

PMID- 25397849
TI  - Day 2. Posters - physical activity for health.

PMID- 25397850
TI  - Day 2. Posters - physiology and nutrition.

PMID- 25397851
TI  - Day 2. Posters - psychology.

PMID- 25397852
TI  - Day 2. Posters - sport and performance.

PMID- 25397854
TI  - Conference programme.

PMID- 25397855
TI  - The Effects of Hospital Safety Scores, Total Price, Out-of-Pocket Cost, and
      Household Income on Consumers' Self-reported Choice of Hospitals.
AB  - OBJECTIVES: The study measured the relative influence of the following 3 factors
      in consumers' choice of hospitals: (1) cost, (2) out-of-pocket cost, and (3)
      safety as measured by Leapfrog Hospital Safety Score letter grade. METHODS: Two
      hospital-choice questions regarding a hypothetical medical procedure were
      administered to 2357 online respondents. In question 1, respondents were assigned
      a scenario in which hospital 1 grade (A through D), hospital 2 grade (B through
      F), and hospital 2 total cost (3 levels) were randomly varied across respondents.
      In all cases, hospital 2 had a lower safety grade than hospital 1, and hospital 1
      cost was held constant. In question 2, scenarios varied out-of-pocket cost rather
      than total cost. Demographic characteristics, income level, health status, health
      literacy, and opinions about value were also measured. RESULTS: On average, 94%
      and 88% of the respondents chose the safer hospital in questions 1 and 2,
      respectively. In all but 1 of 30 possible scenarios, where hospital 2 cost the
      individual $1000 less and was rated a B whereas hospital 1 was rated an A,
      respondents chose the safer hospital. Higher incomes, higher health literacy, and
      being female were associated with a stronger preference for hospital 1 (safer).
      There was a small effect suggesting that approximately 4% of the respondents
      selected a higher-cost hospital despite lower safety, but it was outweighed by
      predominant selections of the safer hospital. CONCLUSIONS: When shown Hospital
      Safety Score and cost information, consumers chose safer hospitals in 97% of cost
      and safety scenarios.

PMID- 25397856
TI  - Medical Harm: Patient Perceptions and Follow-up Actions.
AB  - OBJECTIVES: Much research has been conducted to describe medical mistakes
      resulting in patient harm using databases that capture these events for medical
      organizations. The objective of this study was to describe patients' perceptions
      regarding disclosure and their actions after harm. METHODS: We analyzed a patient
      harm survey database composed of responses from a voluntary online survey
      administered to patients by ProPublica, an independent nonprofit news
      organization, during a 1-year period (May 2012 to May 2013). We collected data on
      patient demographics and characteristics related to the acknowledgment of patient
      harms, the reporting of patient harm to an oversight agency, whether the patient
      or the family obtained the harm-associated medical records, as well as the
      presence of a malpractice claim. RESULTS: There were 236 respondents reporting a
      patient harm (mean age, 49.1 y). In 11.4% (27/236) of harms, an apology by the
      medical organization or the clinician was made. In 42.8% (101/236) of harms, a
      complaint was filed with an oversight agency. In 66.5% (157/236) of harms, the
      patient or the family member obtained a copy of the pertinent medical records. A
      malpractice claim was reported in 19.9% (47/236) of events. CONCLUSIONS: In this
      sample of self-reported patient harms, we found a perception of inadequate
      apology. Nearly half of patient harm events are reported to an oversight agency,
      and roughly one-fifth result in a malpractice claim.

PMID- 25397857
TI  - Interhospital Facility Transfers in the United States: A Nationwide Outcomes
      Study.
AB  - OBJECTIVES: Patient transfers between hospitals are becoming more common in the
      United States. Disease-specific studies have reported varying outcomes associated
      with transfer status. However, even as national quality improvement efforts and
      regulations are being actively adopted, forcing hospitals to become financially
      accountable for the quality of care provided, surprisingly little is known about
      transfer patients or their outcomes at a population level. This population-wide
      study provides timely analyses of the characteristics of this particularly
      vulnerable and sizable inpatient population. We identified and compared
      characteristics and outcomes of transfer and nontransfer patients. METHODS: With
      the use of the 2009 Nationwide Inpatient Sample, a nationally representative
      sample of U.S. hospitalizations, we examined patient characteristics, in-hospital
      adverse events, and discharge disposition for transfer versus nontransfer
      patients in this observational study. RESULTS: We identified 1,397,712 transfer
      patients and 31,692,211 nontransfer patients. Age, sex, race, and payer were
      significantly associated with odds of transfer (P < 0.05). Transfer patients had
      higher risk-adjusted inpatient mortality (4.6 versus 2.1, P < 0.01), longer
      length of stay (13.3 versus 4.5, P < 0.01), and fewer routine disposition
      discharges (53.6 versus 68.7, P < 0.01). In-hospital adverse events were
      significantly higher in transfer patients compared with nontransfer patients (P <
      0.05). CONCLUSIONS: Our results suggest that transfer patients have inferior
      outcomes compared with nontransfer patients. Although they are clinically complex
      patients and assessing accountability as between the transferring and receiving
      hospitals is methodologically difficult, transfer patients must nonetheless be
      included in quality benchmark data to assess the potential impact this population
      has on hospital outcome profiles. With hospital accountability and value-based
      payments constituting an integral part of health care reform, documenting the
      quality of care delivered to transfer patients is essential before accurate
      quality assessment improvement efforts can begin in this patient population.

PMID- 25397858
TI  - Satisfaction with housing and housing support for people with psychiatric
      disabilities.
AB  - The aim of this study was to investigate the degree of satisfaction with housing
      and housing support for people with psychiatric disabilities in Sweden. A total
      of 370 residents, in supported housing and in ordinary housing with housing
      support, completed a new questionnaire and reported a high degree of overall
      satisfaction, but many of them wanted to move somewhere else. Differences were
      found between the two different types of housing concerning satisfaction with
      housing support, social life and available choices. Security and privacy, as well
      as other's influence on the choice of residential area and dwelling proved to be
      important predictors for satisfaction. 

PMID- 25397859
TI  - Rate of new HIV diagnoses among Latinos living in Florida: disparities by
      country/region of birth.
AB  - HIV incidence in the USA is three times higher for Latinos than for non-Latino
      whites. Latinos differ in educational attainment, poverty, insurance coverage,
      and health-care access, factors that affect HIV knowledge, risk behaviors, and
      testing. The purpose of this study was to identify differences in demographics,
      risk factors, and rate of new HIV diagnoses by birth country/region among Latinos
      in Florida to guide the targeting of primary and secondary prevention programs.
      Using Florida HIV/AIDS surveillance data from 2007 to 2011 and the American
      Community Survey, we compared demographic and risk factors, and calculated annual
      and five-year age-adjusted rates of new HIV diagnoses for 5801 Latinos by birth
      country/region. Compared to US-born Latinos, those born in Cuba and South America
      were significantly more likely to report the HIV transmission mode of MSM; those
      born in the Dominican Republic (DR) heterosexual transmission; and those born in
      Puerto Rico injection drug use. Mexican- and Central American-born Latinos were
      more likely to be diagnosed with AIDS within a month of HIV diagnosis. The rate
      of new HIV diagnoses among Latinos declined 33% from 2007 to 2011. HIV diagnoses
      over time decreased significantly for Latinos born in Mexico and increased
      nonsignificantly for those born in the DR. Although this study was limited to
      Latinos living in Florida, results suggest that tailoring HIV primary prevention
      and testing initiatives to specific Latino groups may be warranted. 

PMID- 25397860
TI  - Feature-level analysis of a novel smartphone application for smoking cessation.
AB  - BACKGROUND: Currently, there are over 400 smoking cessation smartphone apps
      available, downloaded an estimated 780,000 times per month. No prior studies have
      examined how individuals engage with specific features of cessation apps and
      whether use of these features is associated with quitting. OBJECTIVES: Using data
      from a pilot trial of a novel smoking cessation app, we examined: (i) the 10 most
      used app features, and (ii) prospective associations between feature usage and
      quitting. METHODS: Participants (n = 76) were from the experimental arm of a
      randomized, controlled pilot trial of an app for smoking cessation called
      "SmartQuit," which includes elements of both Acceptance and Commitment Therapy
      (ACT) and traditional cognitive behavioral therapy (CBT). Utilization data were
      automatically tracked during the 8-week treatment phase. Thirty-day point
      prevalence smoking abstinence was assessed at 60-day follow-up. RESULTS: The most
      used features - quit plan, tracking, progress, and sharing - were mostly CBT.
      Only two of the 10 most-used features were prospectively associated with
      quitting: viewing the quit plan (p = 0.03) and tracking practice of letting urges
      pass (p = 0.03). Tracking ACT skill practice was used by fewer participants (n =
      43) but was associated with cessation (p = 0.01). CONCLUSIONS: In this
      exploratory analysis without control for multiple comparisons, viewing a quit
      plan (CBT) as well as tracking practice of letting urges pass (ACT) were both
      appealing to app users and associated with successful quitting. Aside from these
      features, there was little overlap between a feature's popularity and its
      prospective association with quitting. Tests of causal associations between
      feature usage and smoking cessation are now needed.

PMID- 25397861
TI  - Age-related decline in the reflexive component of overt gaze following.
AB  - Previous research has found age-related declines in social perception tasks as
      well as the ability to engage in joint attention and orienting covert attention
      (i.e., absence of eye movements) in response to an eye gaze cue. We used an overt
      gaze following task to explore age differences in overt gaze following whilst
      people searched for a target. Participants were faster to detect targets
      appearing at the looked-at location, and although the gaze cue biased the
      direction in which saccades were executed, no age differences were found in overt
      gaze following. There were, however, age effects relating to involuntary eye
      movements. In the younger adults, anticipatory saccades were biased in the
      direction of the gaze cue, but this bias was not observed in the older group.
      Moreover, in the younger adults, saccades that followed the gaze were initiated
      more rapidly, illustrating the reflexive nature of gaze following. No such
      difference was observed in the older adults. Importantly, our results showed that
      whilst the general levels of gaze following were age invariant, there were age
      related differences in the reflexive components of overt gaze following. 

PMID- 25397862
TI  - Mental Health Symptoms Among Student Service Members/Veterans and Civilian
      College Students.
AB  - OBJECTIVE: The aim of this study was to investigate if and to what extent student
      service members/veterans differ from civilian college students in the prevalence
      of self-reported symptoms of poor mental health. PARTICIPANTS: The Fall 2011
      implementation of the American College Health Association-National College Health
      Assessment included 27,774 respondents from 44 colleges and universities.
      METHODS: Participants were matched using propensity scores, and the prevalence of
      symptoms was compared using logistic regression and zero-inflated negative
      binomial regression models. RESULTS: The odds of feeling overwhelmed in the last
      12 months were significantly lower among student service members/veterans with a
      history of hazardous duty (odd ratio [OR] = 0.46, adjusted p value <.05) compared
      with civilian students. Military service, with and without hazardous duty
      deployment, was not a significant predictor of the total number of symptoms of
      poor mental health. CONCLUSIONS: Current student service members/veterans may not
      be disproportionately affected by poor psychological functioning.

PMID- 25397863
TI  - Serratus Anterior and Lower Trapezius Muscle Activities During Multi-Joint
      Isotonic Scapular Exercises and Isometric Contractions.
AB  - Context :  Proper scapular function during humeral elevation, such as upward
      rotation, external rotation, and posterior tilting of the scapula, is necessary
      to prevent shoulder injury. However, the appropriate intensity of rehabilitation
      exercise for the periscapular muscles has yet to be clarified. Objective :  To
      identify the serratus anterior, lower trapezius, infraspinatus, and posterior
      deltoid muscle activities during 2 free-motion exercises using 3 intensities and
      to compare these muscle activities with isometric contractions during quadruped
      shoulder flexion and external rotation and abduction of the glenohumeral joint.
      Design :  Cross-sectional study. Setting :  Health Science Laboratory. Patients
      or Other Participants :  A total of 16 uninjured, healthy, active, male college
      students (age = 19.5 +/- 1.2 years, height = 173.1 +/- 6.5 cm, weight = 68.8 +/-
      6.6 kg). Main Outcome Measure(s) :  Mean electromyographic activity normalized by
      the maximal voluntary isometric contraction was analyzed across 3 intensities and
      5 exercises. Intraclass correlation coefficients were calculated for
      electromyographic activity of the 4 muscles in each free-motion exercise. Results
      :  Significant interactions in electromyographic activity were observed between
      intensities and exercises (P < .05). The quadruped shoulder-flexion exercise
      activated all 4 muscles compared with other exercises. Also, the modified robbery
      free-motion exercise activated the serratus anterior, lower trapezius, and
      infraspinatus compared with the lawn-mower free-motion exercise. However, neither
      exercise showed a difference in posterior deltoid electromyographic activity.
      Conclusions :  Three intensities exposed the nature of the periscapular muscle
      activities across the different exercises. The free-motion exercise in
      periscapular muscle rehabilitation may not modify serratus anterior, lower
      trapezius, and infraspinatus muscle activities unless knee-joint extension is
      limited.

PMID- 25397864
TI  - Near-infrared light therapy to attenuate strength loss after strenuous resistance
      exercise.
AB  - CONTEXT: Near-infrared (NIR) light therapy is purported to act as an ergogenic
      aid by enhancing the contractile function of skeletal muscle. Improving muscle
      function is a new avenue for research in the area of laser therapy; however, very
      few researchers have examined the ergogenic effects of NIR light therapy and the
      influence it may have on the recovery process during rehabilitation. OBJECTIVE:
      To evaluate the ergogenic effect of NIR light therapy on skeletal muscle
      function. DESIGN: Crossover study. SETTING: Controlled laboratory. PATIENTS OR
      OTHER PARTICIPANTS: Thirty-nine healthy men (n = 21) and women (n = 18; age =
      20.0 +/- 0.2 years, height = 169 +/- 2 cm, mass = 68.4 +/- 1.8 kg, body mass
      index = 23.8 +/- 0.4 kg/m(2)). INTERVENTION(S): Each participant received active
      and sham treatments on the biceps brachii muscle on 2 separate days. The order of
      treatment was randomized. A class 4 laser with a cumulative dose of 360 J was
      used for the active treatment. After receiving the treatment on each day,
      participants completed an elbow-flexion resistance-exercise protocol. MAIN
      OUTCOME MEASURE(S): The dependent variables were elbow range of motion, muscle
      point tenderness, and strength (peak torque). Analysis of variance with repeated
      measures was used to assess changes in these measures between treatments at
      baseline and at follow-up, 48 hours postexercise. Additionally, immediate
      strength loss postexercise was compared between treatments using a paired t test.
      RESULTS: Preexercise to postexercise strength loss for the active laser
      treatment, although small, was less than with the sham treatment (P = .05).
      CONCLUSIONS: Applied to skeletal muscle before resistance exercise, NIR light
      therapy effectively attenuated strength loss. Therefore, NIR light therapy may be
      a beneficial, noninvasive modality for improving muscle function during
      rehabilitation after musculoskeletal injury. However, future studies using higher
      treatment doses are warranted.

PMID- 25397865
TI  - BALDEY: A database of auditory lexical decisions.
AB  - In an auditory lexical decision experiment, 5541 spoken content words and
      pseudowords were presented to 20 native speakers of Dutch. The words vary in
      phonological make-up and in number of syllables and stress pattern, and are
      further representative of the native Dutch vocabulary in that most are
      morphologically complex, comprising two stems or one stem plus derivational and
      inflectional suffixes, with inflections representing both regular and irregular
      paradigms; the pseudowords were matched in these respects to the real words. The
      BALDEY ("biggest auditory lexical decision experiment yet") data file includes
      response times and accuracy rates, with for each item morphological information
      plus phonological and acoustic information derived from automatic phonemic
      segmentation of the stimuli. Two initial analyses illustrate how this data set
      can be used. First, we discuss several measures of the point at which a word has
      no further neighbours and compare the degree to which each measure predicts our
      lexical decision response outcomes. Second, we investigate how well four
      different measures of frequency of occurrence (from written corpora, spoken
      corpora, subtitles, and frequency ratings by 75 participants) predict the same
      outcomes. These analyses motivate general conclusions about the auditory lexical
      decision task. The (publicly available) BALDEY database lends itself to many
      further analyses. 

PMID- 25397866
TI  - Pancreatic Islet-Like Three-Dimensional Aggregates Derived From Human Embryonic
      Stem Cells Ameliorate Hyperglycemia in Streptozotocin-Induced Diabetic Mice.
AB  - We previously reported the in vitro differentiation of human embryonic stem cells
      (hESCs) into pancreatic endoderm. Here we demonstrate that islet-like three
      dimensional (3D) aggregates can be derived from the pancreatic endoderm by
      optimizing our previous protocol. Sequential treatment with Wnt3a, activin A, and
      noggin induced a transient upregulation of T and MixL1, followed by increased
      expression of endodermal genes, including FOXA2, SOX17, and CXCR4. Subsequent
      treatment with retinoic acid highly upregulated PDX1 expression. We also show
      that inhibition of sonic hedgehog signaling by bFGF/activin betaB and cotreatment
      with VEGF and FGF7 produced many 3D cellular clusters that express both SOX17 and
      PDX1. We found for the first time that proteoglycans and vimentin(+) mesenchymal
      cells were mainly localized in hESC-derived PDX1(+) clusters. Importantly,
      treatment with chlorate, an inhibitor of proteoglycan sulfation, together with
      inhibition of Notch signaling significantly increased the expression of Neurog3
      and NeuroD1, promoting a transition from PDX1(+) progenitor cells toward mature
      pancreatic endocrine cells. Purified dithizone(+) 3D aggregates generated by our
      refined protocol produced pancreatic hormones and released insulin in response to
      both glucose and pharmacological drugs in vitro. Furthermore, the islet-like 3D
      aggregates decreased blood glucose levels and continued to exhibit pancreatic
      features after transplantation into diabetic mice. Generation of islet-like 3D
      cell aggregates from human pluripotent stem cells may overcome the shortage of
      cadaveric donor islets for future cases of clinical islet transplantation. 

PMID- 25397867
TI  - Effect of painless diabetic neuropathy on pressure pain hypersensitivity
      (hyperalgesia) after acute foot trauma.
AB  - INTRODUCTION AND OBJECTIVE: Acute injury transiently lowers local mechanical pain
      thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy
      on this post-traumatic hyperalgesia, pressure pain perception thresholds after a
      skeletal foot trauma were studied in consecutive persons without and with
      neuropathy (i.e. history of foot ulcer or Charcot arthropathy). DESIGN AND
      METHODS: A case-control study was done on 25 unselected clinical routine patients
      with acute unilateral foot trauma (cases: elective bone surgery; controls:
      sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe
      painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic
      persons. Over 1 week after the trauma, cutaneous pressure pain perception
      threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were
      measured repeatedly, adjacent to the injury and at the opposite foot (pinprick
      stimulators, Algometer II((r))). RESULTS: In the control group, post-traumatic
      DPPPT (but not CPPPT) at the injured foot was reduced by about 15-25%. In the
      case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although
      DPPPT fell post-operatively by about 15-20%, it remained always higher than the
      post-traumatic DPPPT in the control group: over musculus abductor hallucis 615
      kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa
      versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post
      operatively. CONCLUSION: Physiological nociception and post-traumatic
      hyperalgesia to pressure are diminished at the foot with severe painless
      (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to
      'pull away' from any one, even innocuous, mechanical impact in order to avoid
      additional damage is, therefore, lacking.

PMID- 25397869
TI  - Investigation of regeneration kinetics in quantum-dots-sensitized solar cells
      with scanning electrochemical microscopy.
AB  - A fast quantum dots (QDs) regeneration process is necessary for highly efficient
      QDs-sensitized solar cells. Herein, CdSe and CdS QDs regeneration rates (kQD') in
      three redox electrolytes, which are triiodide and iodide ions (I3(-)/I(-)),
      Co(bpy)3(PF6)2 and Co(bpy)3(PF6)3 (Co(3+)/Co(2+)), and 1-methy-1-H-tetrazole-5
      thiolate and its dimer (T2/T(-)), have been first investigated with scanning
      electrochemical microscopy (SECM). The results reveal that the kinetics of QDs
      regeneration depends on the nature of the QDs and the redox shuttles presented in
      QDSSCs. For QDs of CdSe and CdS, the regeneration rate (kQD') in the case of a
      T2/T(-)-based electrolyte is about two times larger than that of Co(3+)/Co(2+)
      and I3(-)/I(-). Additionally, the kQD' for CdSe is about two times larger than
      that of CdS in the same redox shuttle electrolyte, which could be due to a large
      driving force for the reaction between the exited state quantum dots (QD(+)) and
      redox electrolytes.

PMID- 25397868
TI  - Comparison of the biological equivalence of two methods for isolating bone marrow
      mononuclear cells for fabricating tissue-engineered vascular grafts.
AB  - Our approach for fabricating tissue-engineered vascular grafts (TEVG), applied in
      the surgical management of congenital heart disease, is accomplished by seeding
      isolated bone marrow-derived mononuclear cells (BM-MNCs) onto biodegradable
      scaffolds. The current method used for isolation of BM-MNCs is density
      centrifugation in Ficoll. This is a time-consuming, labor-intensive, and operator
      dependent method. We previously demonstrated that a simpler, faster, and operator
      independent method for isolating BM-MNCs using a filter elution technique was
      feasible. In this study, we compare the use of each technique to determine if the
      BM-MNCs isolated by the filtration elution method are biologically equivalent to
      BM-MNCs isolated using density centrifugation. Scaffolds were constructed from a
      nonwoven poly(glycolic acid) fiber mesh coated with 50:50 poly(l-lactide-co-E
      caprolactone) sealant. BM-MNCs were isolated from the bone marrow of syngeneic
      C57BL/6 mice by either density centrifugation with Ficoll or filtration (Ficoll
      vs. Filter), then statically seeded onto scaffolds, and incubated overnight. The
      TEVG were implanted in 10-week-old C57BL/6 mice (n=23 for each group) as inferior
      vena cava interposition grafts and explanted at 14 days for analysis. At 14 days
      after implantation, there were no significant differences in graft patency
      between groups (Ficoll: 87% vs. Filter: 78%, p=0.45). Morphometric analysis by
      hematoxylin and eosin staining showed no difference of graft luminal diameter or
      neointimal thickness between groups (luminal diameter, Ficoll: 620.3+/-82.9 MUm
      vs. Filter: 633.3+/-131.0 MUm, p=0.72; neointimal thickness, Ficoll: 37.9+/-7.8
      MUm vs. Filter: 37.9+/-11.2 MUm, p=0.99). Histologic examination demonstrated
      similar degrees of cellular infiltration and extracellular matrix deposition, and
      endothelial cell coverage on the luminal surface, in either group. Macrophage
      infiltration showed no difference in the number of F4/80-positive cells or
      macrophage phenotypes between the two experimental groups (Ficoll: 2041+/-1048
      cells/mm(2) vs. Filter: 1887+/-907.7 cells/mm(2), p=0.18). We confirmed the
      biological equivalence of BM-MNCs, isolated using either density centrifugation
      or filtration, for making TEVG.

PMID- 25397870
TI  - Delineation of the role of glycosylation in the cytotoxic properties of quercetin
      using novel assays in living vertebrates.
AB  - Quercetin is a plant-derived flavonoid and its cytotoxic properties have been
      widely reported. However, in nature, quercetin predominantly occurs as various
      glycosides. Thus far the cytotoxic activity of these glycosides has not been
      investigated to the same extent as quercetin, especially in animal models. In
      this study, the cytotoxic properties of quercetin (1), hyperoside (quercetin 3-O
      galactoside, 2), isoquercitrin (quercetin 3-O-glucoside, 3), quercitrin
      (quercetin 3-O-rhamnoside, 4), and spiraeoside (quercetin 4'-O-glucoside, 5) were
      directly compared in vitro using assays of cancer cell viability. To further
      characterize the influence of glycosylation in vivo, a novel zebrafish-based
      assay was developed that allows the rapid and experimentally convenient
      visualization of glycoside cleavage in the digestive tract. This assay was
      correlated with a novel human tumor xenograft assay in the same animal model. The
      results showed that 3 is as effective as 1 at inhibiting cancer cell
      proliferation in vivo. Moreover, it was observed that 3 can be effectively
      deglycosylated in the digestive tract. Collectively, these results indicate that
      3 is a very promising drug candidate for cancer therapy, because glycosylation
      confers advantageous pharmacological changes compared with the aglycone, 1.
      Importantly, the development of a novel and convenient fluorescence-based assay
      for monitoring deglycosylation in living vertebrates provides a valuable platform
      for determining the metabolic fate of naturally occurring glycosides. 

PMID- 25397871
TI  - Development of stable Vibrio cholerae O1 Hikojima type vaccine strains co
      expressing the Inaba and Ogawa lipopolysaccharide antigens.
AB  - We describe here the development of stable classical and El Tor V. cholerae O1
      strains of the Hikojima serotype that co-express the Inaba and Ogawa antigens of
      O1 lipopolysaccharide (LPS). Mutation of the wbeT gene reduced LPS perosamine
      methylation and thereby gave only partial transformation into Ogawa LPS on the
      cell surface. The strains express approximately equal amounts of Inaba- and Ogawa
      LPS antigens which are preserved after formalin-inactivation of the bacteria.
      Oral immunizations of both inbred and outbred mice with formalin-inactivated
      whole-cell vaccine preparations of these strains elicited strong intestinal IgA
      anti-LPS as well as serum vibriocidal antibody responses against both Inaba and
      Ogawa that were fully comparable to the responses induced by the licensed Dukoral
      vaccine. Passive protection studies in infant mice showed that immune sera raised
      against either of the novel Hikojima vaccine strains protected baby mice against
      infection with virulent strains of both serotypes. This study illustrates the
      power of using genetic manipulation to improve the properties of bacteria strains
      for use in killed whole-cell vaccines. 

PMID- 25397872
TI  - What's in a name? Developing definitions for common health technology assessment
      product types of the International Network of Agencies for Health Technology
      Assessment (inahta).
AB  - OBJECTIVES: A mapping exercise was undertaken to determine how HTA is being
      described and conducted across the International Network of Agencies for Health
      Technology Assessment (INAHTA), with the aim of harmonizing terminologies and
      approaches. METHODS: Three progressive surveys were undertaken. In 2010, INAHTA
      agencies were asked to provide details on all of their HTA products. In 2013,
      additional information was sought on key methodological characteristics of five
      of the most common HTA product types. Subsequently, final agreement was sought on
      three proposed product types. RESULTS: Forty-five HTA agencies responded to at
      least one of the surveys. In 2010, twenty-one agencies reported publishing over
      seventy named HTA products. Core domains associated with full HTA reports were
      reported by a third of agencies but were labeled differently, so products were
      classified according to product type (n = 17). Agencies producing short, tailored
      products increased between 2010 and 2013, with the publication of rapid reviews
      doubling from 33 percent to 66 percent. In 2013, half of the agencies adapted
      their common HTA products from documents produced by other agencies. A consensus
      (>70 percent) was achieved on definitions for HTA reports, mini-HTAs, and rapid
      reviews. CONCLUSIONS: The product label for an HTA is not always indicative of
      its content. Terminology has, therefore, been agreed to make explicit the trade
      off between rigor and timeliness in three common HTA product types. An INAHTA
      Product Type (IPT) Mark has been created to identify each of these. It is hoped
      this will further facilitate HTA adaptation between agencies and reduce
      duplication of effort.

PMID- 25397873
TI  - Hippocampal state-dependent behavioral reflex to an identical sensory input in
      rats.
AB  - We examined the local field potential of the hippocampus to monitor brain states
      during a conditional discrimination task, in order to elucidate the relationship
      between ongoing brain states and a conditioned motor reflex. Five 10-week-old
      Wistar/ST male rats underwent a serial feature positive conditional
      discrimination task in eyeblink conditioning using a preceding light stimulus as
      a conditional cue for reinforced trials. In this task, a 2-s light stimulus
      signaled that the following 350-ms tone (conditioned stimulus) was reinforced
      with a co-terminating 100-ms periorbital electrical shock. The interval between
      the end of conditional cue and the onset of the conditioned stimulus was 4+/-1 s.
      The conditioned stimulus was not reinforced when the light was not presented.
      Animals successfully utilized the light stimulus as a conditional cue to drive
      differential responses to the identical conditioned stimulus. We found that
      presentation of the conditional cue elicited hippocampal theta oscillations,
      which persisted during the interval of conditional cue and the conditioned
      stimulus. Moreover, expression of the conditioned response to the tone
      (conditioned stimulus) was correlated with the appearance of theta oscillations
      immediately before the conditioned stimulus. These data support hippocampal
      involvement in the network underlying a conditional discrimination task in
      eyeblink conditioning. They also suggest that the preceding hippocampal activity
      can determine information processing of the tone stimulus in the cerebellum and
      its associated circuits. 

PMID- 25397876
TI  - A novel bifunctional hybrid with marine bacterium alkaline phosphatase and Far
      Eastern holothurian mannan-binding lectin activities.
AB  - A fusion between the genes encoding the marine bacterium Cobetia marina alkaline
      phosphatase (CmAP) and Far Eastern holothurian Apostichopus japonicus mannan
      binding C-type lectin (MBL-AJ) was performed. Expression of the fusion gene in E.
      coli cells resulted in yield of soluble recombinant chimeric protein CmAP/MBL-AJ
      with the high alkaline phosphatase activity and specificity of the lectin MBL-AJ.
      The bifunctional hybrid CmAP/MBL-AJ was produced as a dimer with the molecular
      mass of 200 kDa. The CmAP/MBL-AJ dimer model showed the two-subunit lectin part
      that is associated with two molecules of alkaline phosphatase functioning
      independently from each other. The highly active CmAP label genetically linked to
      MBL-AJ has advantaged the lectin-binding assay in its sensitivity and time. The
      double substitution A156N/F159K in the lectin domain of CmAP/MBL-AJ has enhanced
      its lectin activity by 25 +/- 5%. The bifunctional hybrid holothurian's lectin
      could be promising tool for developing non-invasive methods for biological
      markers assessment, particularly for improving the MBL-AJ-based method for early
      detection of a malignant condition in cervical specimens.

PMID- 25397875
TI  - Predictors of children's secondhand smoke exposure at home: a systematic review
      and narrative synthesis of the evidence.
AB  - BACKGROUND: Children's exposure to secondhand smoke (SHS) has been causally
      linked to a number of childhood morbidities and mortalities. Over 50% of UK
      children whose parents are smokers are regularly exposed to SHS at home. No
      previous review has identified the factors associated with children's SHS
      exposure in the home. AIM: To identify by systematic review, the factors which
      are associated with children's SHS exposure in the home, determined by parent or
      child reports and/or biochemically validated measures including cotinine, carbon
      monoxide or home air particulate matter. METHODS: Electronic searches of MEDLINE,
      EMBASE, PsychINFO, CINAHL and Web of Knowledge to July 2014, and hand searches of
      reference lists from publications included in the review were conducted.
      FINDINGS: Forty one studies were included in the review. Parental smoking, low
      socioeconomic status and being less educated were all frequently and consistently
      found to be independently associated with children's SHS exposure in the home.
      Children whose parents held more negative attitudes towards SHS were less likely
      to be exposed. Associations were strongest for parental cigarette smoking status;
      compared to children of non-smokers, those whose mothers or both parents smoked
      were between two and 13 times more likely to be exposed to SHS. CONCLUSION:
      Multiple factors are associated with child SHS exposure in the home; the best way
      to reduce child SHS exposure in the home is for smoking parents to quit. If
      parents are unable or unwilling to stop smoking, they should instigate smoke-free
      homes. Interventions targeted towards the socially disadvantaged parents aiming
      to change attitudes to smoking in the presence of children and providing
      practical support to help parents smoke outside the home may be beneficial.

PMID- 25397877
TI  - pH and ligand dependent assembly of Well-Dawson arsenomolybdate capped
      architectures.
AB  - Five Well-Dawson-type arsenomolybdates, formulated as [Cu(2,2'-bpy)2][{Cu(2,2'
      bpy)}3{As2(V)Mo2(V)Mo16(VI)O62}].4H2O (1), [H2(4,4'
      bpy)]2.5[As(III)(As2(V)Mo2(V)Mo16(VI)O62)].5H2O (2),
      (pyr)(imi)(Himi)3[As2(III)(As2(V)Mo3(V)Mo15(VI)O62)].3H2O (3),
      [As3(III)(As2(V)Mo3(V)Mo15(VI)O62)].4H2O (4), and
      (H2btp)3[As2(V)Mo18(VI)O62].6H2O (5) (bpy = bipyridine, pyr = pyrazine, imi =
      imidazole, btp = 1,5-bis(triazol)pentane), have been hydrothermally synthesized
      and structurally characterized by the elemental analysis, TG, IR, UV-vis-NIR,
      XPS, XRD, and single-crystal X-ray diffraction. The structural analysis indicates
      that compounds 1-4 contain rare reduced Dawson {As2Mo18O62} (abbreviated as
      {As2Mo18}) anions as parent cluster unit, which are capped by a certain number of
      Cu(II) or As(III) species on different coordination positions via altering pH
      values and organic ligand of the reaction system. Compounds 1 and 2 are
      asymmetric tricopper and monoarsenate(III) capped assemble by three {Cu(bpy)}(2+)
      and a {AsO3} fragments, respectively. Compounds 3 and 4 are symmetric
      biarsenate(III) and triarsenate(III) capped cluster by four and six half
      occupancy {AsO3} units, respectively. Compound 5 is uncapped {As2Mo18}
      structures. Compounds 1-4 represent infrequent Dawson arsenomolybdate capped
      architectures, especially 2-4, as arsenate(III) capped Dawson-type assemblies are
      observed for the first time. Compounds 1-5 display good electrocatalytic activity
      on reduction of nitrite. Compounds 1, 2, 3, and 5 exhibit fluorescent properties
      in the solid state at room temperature. In addition, magnetic properties of 1-4
      have been investigated in detail. 

PMID- 25397879
TI  - Application of pharmacokinetic modelling for 2,3,7,8-tetrachlorodibenzo-p-dioxin
      exposure assessment.
AB  - Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and mono- and
      non-ortho polychlorinated biphenyls (dioxin-like PCBs) are identified as a family
      or group of organic compounds known as 'dioxins' or dioxin-like chemicals (DLCs).
      The most toxic member of this group is 2,3,7,8-tetrachlorodibenzo-(p)-dioxin
      (TCDD). Historically, DLCs have caused a variety of negative human health
      effects, but a disfiguring skin condition known as chloracne is the only health
      effect reported consistently. As part of translational research to make
      computerized models accessible to health risk assessors, the Concentration- and
      Age-Dependent Model (CADM) for TCDD was recoded in the Berkeley Madonna
      simulation language. The US Agency for Toxic Substances and Disease Registry's
      computational toxicology laboratory used the recoded model to predict TCDD tissue
      concentrations at different exposure levels. The model simulations successfully
      reproduced the National Health and Nutrition Examination Survey (NHANES) 2001
      2002 TCDD data in age groups from 6 to 60 years and older, as well as in other
      human datasets. The model also enabled the estimation of lipid-normalized serum
      TCDD concentrations in breastfed infants. The model performed best for low
      background exposures over time compared with a high acute poisoning case that
      could due to the large dose and associated liver toxicity. Hence, this model may
      be useful for interpreting human biomonitoring data as a part of an overall DLC
      risk assessment. 

PMID- 25397882
TI  - Gossip-based solutions for discrete rendezvous in populations of communicating
      agents.
AB  - The objective of the rendezvous problem is to construct a method that enables a
      population of agents to agree on a spatial (and possibly temporal) meeting
      location. We introduce the buffered gossip algorithm as a general solution to the
      rendezvous problem in a discrete domain with direct communication between
      decentralized agents. We compare the performance of the buffered gossip algorithm
      against the well known uniform gossip algorithm. We believe that a buffered
      solution is preferable to an unbuffered solution, such as the uniform gossip
      algorithm, because the use of a buffer allows an agent to use multiple
      information sources when determining its desired rendezvous point, and that
      access to multiple information sources may improve agent decision making by
      reinforcing or contradicting an initial choice. To show that the buffered gossip
      algorithm is an actual solution for the rendezvous problem, we construct a
      theoretical proof of convergence and derive the conditions under which the
      buffered gossip algorithm is guaranteed to produce a consensus on rendezvous
      location. We use these results to verify that the uniform gossip algorithm also
      solves the rendezvous problem. We then use a multi-agent simulation to conduct a
      series of simulation experiments to compare the performance between the buffered
      and uniform gossip algorithms. Our results suggest that the buffered gossip
      algorithm can solve the rendezvous problem faster than the uniform gossip
      algorithm; however, the relative performance between these two solutions depends
      on the specific constraints of the problem and the parameters of the buffered
      gossip algorithm. 

PMID- 25397881
TI  - Intronic variants in the NFKB1 gene may influence hearing forecast in patients
      with unilateral sensorineural hearing loss in Meniere's disease.
AB  - Meniere's disease is an episodic vestibular syndrome associated with
      sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated
      prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus
      erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared
      autoimmune background. Functional variants of several genes involved in the NF
      kappaB pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with
      two or more immune-mediated diseases and allelic variations in the TLR10 gene may
      influence bilateral affectation and clinical course in MD. We have genotyped 716
      cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping
      array containing 186 autoimmune loci, to explore the association of immune system
      related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP)
      reached a genome-wide significant association (p<10(-8)), we selected allelic
      variants in the NF-kB pathway for further analyses to evaluate the impact of
      these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs
      increased susceptibility for MD in patients with uni or bilateral SNHL. However,
      two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011)
      were associated with a faster hearing loss progression in patients with
      unilateral SNHL. So, individuals with unilateral MD carrying the C allele in
      rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage
      3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and
      p = 0.003 for rs4648011, respectively). No variants influenced hearing in
      bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011
      can modify hearing outcome in patients with MD and unilateral SNHL.

PMID- 25397883
TI  - Trapped state sensitive kinetics in LaTiO2N solid photocatalyst with and without
      cocatalyst loading.
AB  - In addition to the process of photogeneration of electrons and holes in
      photocatalyst materials, the competitive process of trapping of these charge
      carriers by existing defects, which can both enhance the photocatalytic activity
      by promoting electron-hole separation or can deteriorate the activity by serving
      as recombination centers, is also very crucial to the overall performance of the
      photocatalyst. In this work, using femtosecond diffuse reflectance spectroscopy
      we have provided evidence for the existence of energetically distributed trapped
      states in visible-light responsive solid photocatalyst powder material LaTiO2N
      (LTON). We observe trapped state sensitive kinetics in bare-LTON. CoOx cocatalyst
      loading (2 wt % CoOx-LTON) shows effect on the kinetics only when presence of
      excess energy (for above bandgap excitation) results in the generation of surface
      carriers. Thus, the kinetics show appreciable excitation wavelength dependence,
      and the experimental results obtained for different lambdaexc have been
      rationalized on this basis. In an earlier work by Domen and co-workers, the
      optimized CoOx/LTON has been reported to exhibit a high quantum efficiency of
      27.1 +/- 2.6% at 440 nm, the highest reported for this class of photocatalysts
      (J. Am. Chem. Soc. 2012, 134, 8348-8351). In the present work, the mechanism is
      addressed in terms of picosecond charge carrier dynamics. 

PMID- 25397880
TI  - Detection of tumor cell-specific mRNA and protein in exosome-like microvesicles
      from blood and saliva.
AB  - The discovery of disease-specific biomarkers in oral fluids has revealed a new
      dimension in molecular diagnostics. Recent studies have reported the mechanistic
      involvement of tumor cells derived mediators, such as exosomes, in the
      development of saliva-based mRNA biomarkers. To further our understanding of the
      origins of disease-induced salivary biomarkers, we here evaluated the hypothesis
      that tumor-shed secretory lipidic vesicles called exosome-like microvesicles
      (ELMs) that serve as protective carriers of tissue-specific information, mRNAs,
      and proteins, throughout the vasculature and bodily fluids. RNA content was
      analyzed in cell free-saliva and ELM-enriched fractions of saliva. Our data
      confirmed that the majority of extracellular RNAs (exRNAs) in saliva were
      encapsulated within ELMs. Nude mice implanted with human lung cancer H460 cells
      expressing hCD63-GFP were used to follow the circulation of tumor cell specific
      protein and mRNA in the form of ELMs in vivo. We were able to identify human
      GAPDH mRNA in ELMs of blood and saliva of tumor bearing mice using nested RT
      qPCR. ELMs positive for hCD63-GFP were detected in the saliva and blood of tumor
      bearing mice as well as using electric field-induced release and measurement
      (EFIRM). Altogether, our results demonstrate that ELMs carry tumor cell-specific
      mRNA and protein from blood to saliva in a xenografted mouse model of human lung
      cancer. These results therefore strengthen the link between distal tumor
      progression and the biomarker discovery of saliva through the ELMs. 

PMID- 25397884
TI  - Excitatory amino acid receptors mediate asymmetry and lateralization in the
      descending cardiovascular pathways from the dorsomedial hypothalamus.
AB  - The dorsomedial hypothalamus (DMH) and lateral/dorsolateral periaqueductal gray
      (PAG) are anatomically and functionally connected. Both the DMH and PAG depend on
      glutamatergic inputs for activation. We recently reported that removal of GABA
      ergic tone in the unilateral DMH produces: asymmetry, that is, a right- (R-)
      sided predominance in cardiac chronotropism, and lateralization, that is, a
      greater increase in ipsilateral renal sympathetic activity (RSNA). In the current
      study, we investigated whether excitatory amino acid (EAA) receptors in the DMH
      PAG pathway contribute to the functional interhemispheric difference. In urethane
      (1.2 to 1.4 g/kg, i.p.) anesthetized rats, we observed that: (i) nanoinjections
      of N-methyl D-aspartate (NMDA 100 pmol/100 nl) into the unilateral DMH produced
      the same right-sided predominance in the control of cardiac chronotropy, (ii)
      nanoinjections of NMDA into the ipsilateral DMH or PAG evoked lateralized RSNA
      responses, and (iii) blockade of EAA receptors in the unilateral DMH attenuated
      the cardiovascular responses evoked by injection of NMDA into either the R- or
      left- (L-) PAG. In awake rats, nanoinjection of kynurenic acid (1 nmol/100 nL)
      into the L-DMH or R- or L-PAG attenuated the tachycardia evoked by air stress.
      However, the magnitude of stress-evoked tachycardia was smallest when the EAA
      receptors of the R-DMH were blocked. We conclude that EAA receptors contribute to
      the right-sided predominance in cardiac chronotropism. This interhemispheric
      difference that involves EAA receptors was observed in the DMH but not in the
      PAG. 

PMID- 25397885
TI  - Hypertriglyceridemic waist and metabolic abnormalities in Brazilian
      schoolchildren.
AB  - OBJECTIVE: To identify the prevalence of hypertriglyceridemic waist (HTW)
      phenotype and its association with metabolic abnormalities in schoolchildren.
      METHODS: A cross-sectional study, with a sample of 241 students aged 10 to 14
      years from public schools (4 schools) and private (2 schools) from Paranavai
      town, in Parana State, Brazil. Anthropometric variables (weight, height, waist
      circumference) and levels of triglycerides, total cholesterol, HDL-C, non-HDL and
      LDL-C were analyzed. In statistical tests of Pearson partial correlation and
      multivariate logistic regression, considering p<0,05. RESULTS: The prevalence of
      HTW was 20,7% among schoolchildren, 14,1% in males and 6,6% among females with
      higher proportions aged 10-12 years old. Multivariate analysis indicated that the
      students who attended private schools were nearly three times more likely (95%
      CI: 1,2-5,6), to be diagnosed with HTW compared with those who attended public
      schools (p = 0,006), and LDL-C was the only metabolic variable positively
      associated with the outcome (p = 0,001), where the students categorized with
      elevated serum levels had odds 4,2 times (95% CI: 1,6-10,9) having the HTW
      compared to students in appropriate levels. CONCLUSION: This study showed higher
      prevalence of hypertriglyceridemic waist phenotype in students when compared to
      prospective studies in Brazil and worldwide. It also showed that the only
      metabolic alteration associated with HTW phenotype was LDL-C (low density
      lipoprotein).

PMID- 25397886
TI  - Burst strength of tubing and casing based on twin shear unified strength theory.
AB  - The internal pressure strength of tubing and casing often cannot satisfy the
      design requirements in high pressure, high temperature and high H2S gas wells.
      Also, the practical safety coefficient of some wells is lower than the design
      standard according to the current API 5C3 standard, which brings some perplexity
      to the design. The ISO 10400: 2007 provides the model which can calculate the
      burst strength of tubing and casing better than API 5C3 standard, but the
      calculation accuracy is not desirable because about 50 percent predictive values
      are remarkably higher than real burst values. So, for the sake of improving
      strength design of tubing and casing, this paper deduces the plastic limit
      pressure of tubing and casing under internal pressure by applying the twin shear
      unified strength theory. According to the research of the influence rule of yield
      to-tensile strength ratio and mechanical properties on the burst strength of
      tubing and casing, the more precise calculation model of tubing-casing's burst
      strength has been established with material hardening and intermediate principal
      stress. Numerical and experimental comparisons show that the new burst strength
      model is much closer to the real burst values than that of other models. The
      research results provide an important reference to optimize the tubing and casing
      design of deep and ultra-deep wells. 

PMID- 25397887
TI  - Canine hip dysplasia - towards more effective selection.

PMID- 25397888
TI  - Adipose hypothermia in obesity and its association with period homolog 1, insulin
      sensitivity, and inflammation in fat.
AB  - Visceral fat adiposity plays an important role in the development of metabolic
      syndrome. We reported previously the impact of human visceral fat adiposity on
      gene expression profile of peripheral blood cells. Genes related to circadian
      rhythm were highly associated with visceral fat area and period homolog 1 (PER1)
      showed the most significant negative correlation with visceral fat area. However,
      regulation of adipose Per1 remains poorly understood. The present study was
      designed to understand the regulation of Per1 in adipose tissues. Adipose Per1
      mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels
      of other core clock genes of white adipose tissues were also low in ob/ob mice at
      25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte
      fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the
      possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis
      factor-alpha (TNF-alpha), S100A8, and lipopolysaccharide (LPS). However, no
      significant changes in Per1 mRNA level were observed by these agents. Exposure of
      cultured 3T3-L1 adipocytes to low temperature (33 degrees C) decreased Per1 and
      catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels.
      Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1
      adipocytes. Finally, telemetric analysis showed low temperature of adipose
      tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate
      adipocyte dysfunction. 

PMID- 25397889
TI  - Small quantum dots conjugated to nanobodies as immunofluorescence probes for
      nanometric microscopy.
AB  - Immunofluorescence, a powerful technique to detect specific targets using
      fluorescently labeled antibodies, has been widely used in both scientific
      research and clinical diagnostics. The probes should be made with small
      antibodies and high brightness. We conjugated GFP binding protein (GBP)
      nanobodies, small single-chain antibodies from llamas, with new ~7 nm quantum
      dots. These provide simple and versatile immunofluorescence nanoprobes with
      nanometer accuracy and resolution. Using the new probes we tracked the walking of
      individual kinesin motors and measured their 8 nm step sizes; we tracked Piezo1
      channels, which are eukaryotic mechanosensitive channels; we also tracked AMPA
      receptors on living neurons. Finally, we used a new super-resolution algorithm
      based on blinking of (small) quantum dots that allowed ~2 nm precision. 

PMID- 25397890
TI  - Intrauterine device insertion in the postpartum period: a systematic review.
AB  - OBJECTIVES: Given new research on postpartum placement of levonorgestrel and
      copper intrauterine devices (IUDs), our objective was to update a prior
      systematic review of the safety and expulsion rates of postpartum IUDs. METHODS:
      We searched MEDLINE, CENTRAL, LILACS, POPLINE, Web of Science, and
      ClinicalTrials.gov databases for articles between the database inception until
      July 2013. We included studies that compared IUD insertion time intervals and
      routes during the postpartum period. We used standard abstract forms and the
      United States Preventive Services Task Force grading system to summarise and
      assess the quality of the evidence. RESULTS: We included 18 articles. New
      evidence suggests that a levonorgestrel releasing-intrauterine system (LNG-IUS)
      insertion within 48 hours of delivery is safe. Postplacental insertion and
      insertion between 10 minutes and 48 hours after delivery result in higher
      expulsion rates than insertion 4 to 6 weeks postpartum, or non-postpartum
      insertion. Insertion at the time of caesarean section is associated with lower
      expulsion rates than postplacental insertion at the time of vaginal delivery.
      CONCLUSIONS: This review supports the evidence that insertion of an intrauterine
      contraceptive within the first 48 hours of vaginal or caesarean delivery is safe.
      Expulsion rates should be further studied in larger randomised controlled trials.

PMID- 25397891
TI  - Photothermal laser fabrication of micro- and nanostructured chemical templates
      for directed protein immobilization.
AB  - Photothermal patterning of poly(ethylene glycol) terminated organic monolayers on
      surface-oxidized silicon substrates is carried out using a microfocused beam of a
      CW laser operated at a wavelength of 532 nm. Trichlorosilane and trimethoxysilane
      precursors are used for coating. Monolayers from trimethoxysilane precursors show
      negligible unspecific protein adsorption in the background, i.e., provide
      platforms of superior protein repellency. Laser patterning results in
      decomposition of the monolayers and yields chemical templates for directed
      immobilization of proteins at predefined positions. Characterization is carried
      out via complementary analytical methods including fluorescence microscopy,
      atomic force microscopy, and scanning electron microscopy. Appropriate labeling
      techniques (fluorescent markers and gold clusters) and substrates (native and
      thermally oxidized silicon substrates) are chosen in order to facilitate
      identification of protein adsorption and ensure high sensitivity and selectivity.
      Variation of the laser parameters at a 1/e(2) spot diameter of 2.8 MUm allows for
      fabrication of protein binding domains with diameters on the micrometer and
      nanometer length scale. Minimum domain sizes are about 300 nm. In addition to
      unspecific protein adsorption on as-patterned monolayers, biotin-streptavidin
      coupling chemistry is exploited for specific protein binding. This approach
      represents a novel facile laser-based means for fabrication of protein micro- and
      nanopatterns. The routine is readily applicable to femtosecond laser processing
      of glass substrates for the fabrication of transparent templates. 

PMID- 25397892
TI  - Human gut dendritic cells drive aberrant gut-specific t-cell responses in
      ulcerative colitis, characterized by increased IL-4 production and loss of IL-22
      and IFNgamma.
AB  - : The pathogenesis of inflammatory bowel disease is incompletely understood but
      results from a dysregulated intestinal immune response to the luminal microbiota.
      CD4 T cells mediate tissue injury in the inflammatory bowel disease-associated
      immune response. Dendritic cells (DC) generate primary T-cell responses and
      mediate intestinal immune tolerance to prevent overt inflammation in response to
      the gut microbiota. However, most information regarding function of intestinal DC
      has come from mouse models, and information in humans is scarce. We show here
      that intestinal DC subsets are skewed in ulcerative colitis (UC) in humans, with
      a loss of CD103 lymph-node homing DC; this intestinal DC subset preferentially
      generates regulatory T cells in mice. We show infiltrates of DC negative for
      myeloid marker CD11c, with enhanced expression of Toll-like receptors for
      bacterial recognition. After mixed leukocyte reaction, DC from the inflamed UC
      colon had an enhanced ability to generate gut-specific CD4 T cells with enhanced
      production of interleukin-4 but a loss of interferon gamma and interleukin-22
      production. Conditioning intestinal DC with probiotic strain Lactobacillus casei
      Shirota in UC partially restored their normal function indicated by reduced Toll
      like receptor 2/4 expression and restoration of their ability to imprint homing
      molecules on T cells and to generate interleukin-22 production by stimulated T
      cells. This study suggests that T-cell dysfunction in UC is driven by DC. T-cell
      responses can be manipulated indirectly through effects of bacterial conditioning
      on gut DC with implications for immunomodulatory effects of the commensal
      microbiota in vivo. Manipulation of DC to allow generation of DC-specific therapy
      may be beneficial in inflammatory bowel disease. 

PMID- 25397894
TI  - Reply to managing patients with ulcerative colitis with infliximab in primary and
      referral gastroenterology centers.

PMID- 25397893
TI  - Molecular patterns in human ulcerative colitis and correlation with response to
      infliximab.
AB  - BACKGROUND: As a T cell-mediated disease of the colonic epithelium, ulcerative
      colitis (UC) is likely to share pathogenic elements with other T cell-mediated
      inflammatory diseases. Recently, microarray analysis revealed large-scale
      molecular changes in T cell-mediated rejection of kidney and heart transplants.
      We hypothesized that similar disturbances might be operating in UC and could
      provide insights into responsiveness to therapy. METHODS: We studied 56 colon
      biopsies from patients with colitis characterizing the clinical and histological
      features and using microarrays to define the messenger RNA phenotype. We
      expressed the microarray results using previously defined pathogenesis-based
      transcript sets. We also studied 48 published microarray files from human colon
      biopsies downloaded from the Gene Expression Omnibus database, classified by
      response to infliximab therapy, to examine whether the molecular measurements
      derived from our studies correlated with nonresponsiveness to treatment. RESULTS:
      UC biopsies manifested coordinate transcript changes resembling rejecting
      transplants, with effector T cell, IFNG-induced, macrophage, and injury
      transcripts increasing while parenchymal transcripts decreased. The disturbance
      in gene expression, summarized as principal component 1 (PC1), correlated with
      conventional clinical and histologic assessments. When assessed in microarray
      results from published studies, the disturbance (PC1) predicted response to
      infliximab: patients with intense disturbance did not achieve clinical response,
      although quantitative improvement was seen even in many clinical nonresponders.
      Similar changes were seen in Crohn's colitis. CONCLUSIONS: The molecular
      phenotype of UC manifests a large-scale coordinate disturbance reflecting changes
      in inflammatory cells and parenchymal elements that correlates with conventional
      features and predicts response to infliximab.

PMID- 25397895
TI  - Incorrect citation and analysis in meta-analysis.

PMID- 25397896
TI  - Reply to does cigarette smoke extract really bring out different effects on
      dendritic cells from ulcerative colitis and Crohn's disease?

PMID- 25397897
TI  - Multivariate analysis reveals differences in biofilm formation capacity among
      Listeria monocytogenes lineages.
AB  - Biofilm formation capacity evaluated under identical conditions differs among
      Listeria monocytogenes lineages. The approach of using one set of factors or one
      variable at a time fails to explain why some lineages are more prevalent than
      others in certain environments. This study proposes the use of multivariate
      analysis to compare biofilm formation by various strains and describes the
      ecological niches of L. monocytogenes lineages. Nutrient availability,
      temperature, pH and water activity (aw) at three different levels were used to
      determine biofilm formation by 41 strains. Despite the high degree of similarity
      (<= 80%), distinct lineage-associated biofilm formation patterns were identified.
      A linear regression model for each strain and a principal component analysis of
      regression coefficients indicated that Lineages I and III have different, but
      overlapping, ecological niches. This study is the first to report the use of
      multivariate analyses to compare biofilm formation by various isolates of L.
      monocytogenes. 

PMID- 25397899
TI  - Fabrication of porous carbon/TiO2 composites through polymerization-induced phase
      separation and use as an anode for Na-ion batteries.
AB  - Polymerization-induced phase separation of nanoparticle-filled solution is
      demonstrated as a simple approach to control the structure of porous composites.
      These composites are subsequently demonstrated as the active component for sodium
      ion battery anode. To synthesize the composites, we dissolved/dispersed titanium
      oxide (anatase) nanoparticles (for sodium insertion) and poly(hydroxybutyl
      methacrylate) (PHBMA, porogen) in furfuryl alcohol (carbon precursor) containing
      a photoacid generator (PAG). UV exposure converts the PAG to a strong acid that
      catalyzes the furfuryl alcohol polymerization. This polymerization simultaneously
      decreases the miscibility of the PHBMA and reduces the mobility in the mixture to
      kinetically trap the phase separation. Carbonization of this polymer composite
      yields a porous nanocomposite. This nanocomposite exhibits nearly 3-fold greater
      gravimetric capacity in Na-ion batteries than the same titanium oxide
      nanoparticles that have been coated with carbon. This improved performance is
      attributed to the morphology as the carbon content in the composite is five times
      that of the coated nanoparticles. The porous composite materials exhibit stable
      cyclic performance. Moreover, the battery performance using materials from this
      polymerization-induced phase separation method is reproducible (capacity within
      10% batch-to-batch). This simple fabrication methodology may be extendable to
      other systems and provides a facile route to generate reproducible hierarchical
      porous morphology that can be beneficial in energy storage applications. 

PMID- 25397898
TI  - Pdsg1 and Pdsg2, novel proteins involved in developmental genome remodelling in
      Paramecium.
AB  - The epigenetic influence of maternal cells on the development of their progeny
      has long been studied in various eukaryotes. Multicellular organisms usually
      provide their zygotes not only with nutrients but also with functional elements
      required for proper development, such as coding and non-coding RNAs. These
      maternally deposited RNAs exhibit a variety of functions, from regulating gene
      expression to assuring genome integrity. In ciliates, such as Paramecium these
      RNAs participate in the programming of large-scale genome reorganization during
      development, distinguishing germline-limited DNA, which is excised, from somatic
      destined DNA. Only a handful of proteins playing roles in this process have been
      identified so far, including typical RNAi-derived factors such as Dicer-like and
      Piwi proteins. Here we report and characterize two novel proteins, Pdsg1 and
      Pdsg2 (Paramecium protein involved in Development of the Somatic Genome 1 and 2),
      involved in Paramecium genome reorganization. We show that these proteins are
      necessary for the excision of germline-limited DNA during development and the
      survival of sexual progeny. Knockdown of PDSG1 and PDSG2 genes affects the
      populations of small RNAs known to be involved in the programming of DNA
      elimination (scanRNAs and iesRNAs) and chromatin modification patterns during
      development. Our results suggest an association between RNA-mediated trans
      generational epigenetic signal and chromatin modifications in the process of
      Paramecium genome reorganization. 

PMID- 25397900
TI  - DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating
      ERK1/2 phosphorylation.
AB  - Protein tyrosine phosphatases have been recognized as critical components of
      multiple signaling regulators of fundamental cellular processes, including
      differentiation, cell death, and migration. In this study, we show that dual
      specificity phosphatase 4 (DUSP4) is crucial for neuronal differentiation and
      functions in the neurogenesis of embryonic stem cells (ESCs). The endogenous mRNA
      and protein expression levels of DUSP4 gradually increased during mouse
      development from ESCs to postnatal stages. Neurite outgrowth and the expression
      of neuron-specific markers were markedly reduced by genetic ablation of DUSP4 in
      differentiated neurons, and these effects were rescued by the reintroduction of
      DUSP4. In addition, DUSP4 knockdown dramatically enhanced extracellular signal
      regulated kinase (ERK) activation during neuronal differentiation. Furthermore,
      the DUSP4-ERK pathway functioned to balance calcium signaling, not only by
      regulating Ca(2+)/calmodulin-dependent kinase I phosphorylation, but also by
      facilitating Cav1.2 expression and plasma membrane localization. These data are
      the first to suggest a molecular link between the MAPK-ERK cascade and calcium
      signaling, which provides insight into the mechanism by which DUSP4 modulates
      neuronal differentiation. 

PMID- 25397901
TI  - Structure-guided DOT1L probe optimization by label-free ligand displacement.
AB  - The DOT1L lysine methyltransferase has emerged as a validated therapeutic target
      in MLL-rearranged (MLLr) acute leukemias. Although S-adenosylmethionine
      competitive inhibitors have demonstrated pharmacological proof-of-principle in
      MLLr-leukemia, these compounds require further optimization to improve cellular
      potency and pharmacokinetic stability. Limiting DOT1L inhibitor discovery and
      ligand optimization have been complex biochemical methods often using
      radionucleotides and cellular methods requiring prolonged culture. We therefore
      developed a new suite of assay technologies that allows comparative assessment of
      chemical tools for DOT1L in a miniaturized format. Coupling these assays with
      structural information, we developed new insights into DOT1L ligand binding and
      identified several functionalized probes with increased cellular potency (IC50
      values ~10 nM) and excellent selectivity for DOT1L. Together these assay
      technologies define a platform capability for discovery and optimization of small
      molecule DOT1L inhibitors.

PMID- 25397902
TI  - Measuring the bright side of being blue: a new tool for assessing analytical
      rumination in depression.
AB  - BACKGROUND: Diagnosis and management of depression occurs frequently in the
      primary care setting. Current diagnostic and management of treatment practices
      across clinical populations focus on eliminating signs and symptoms of
      depression. However, there is debate that some interventions may pathologize
      normal, adaptive responses to stressors. Analytical rumination (AR) is an example
      of an adaptive response of depression that is characterized by enhanced cognitive
      function to help an individual focus on, analyze, and solve problems. To date,
      research on AR has been hampered by the lack of theoretically-derived and
      psychometrically sound instruments. This study developed and tested a clinically
      meaningful measure of AR. METHODS: Using expert panels and an extensive
      literature review, we developed a conceptual framework for AR and 22 candidate
      items. Items were field tested to 579 young adults; 140 of whom completed the
      items at a second time point. We used Rasch measurement methods to construct and
      test the item set; and traditional psychometric analyses to compare items to
      existing rating scales. RESULTS: Data were high quality (<1% missing; high
      reliability: Cronbach's alpha = 0.92, test-retest intraclass correlations >0.81;
      evidence for divergent validity). Evidence of misfit for 2 items suggested that a
      20-item scale with 4-point response categories best captured the concept of AR,
      fitting the Rasch model (chi2 = 95.26; df = 76, p = 0.07), with high reliability
      (rp = 0.86), ordered response scale structure, and no item bias (gender, age,
      time). CONCLUSION: Our study provides evidence for a 20-item Analytical
      Rumination Questionnaire (ARQ) that can be used to quantify AR in adults who
      experience symptoms of depression. The ARQ is psychometrically robust and a
      clinically useful tool for the assessment and improvement of depression in the
      primary care setting. Future work is needed to establish the validity of this
      measure in people with major depression.

PMID- 25397904
TI  - H1-antihistamines for chronic spontaneous urticaria.
AB  - Background Chronic spontaneous urticaria (CSU) is characterised by the
      development of crops of red, itchy, raised weals or hives with no identifiable
      external cause.Objectives To assess the effects of H1-antihistamines for
      CSU.Search methods We searched the following databases up to June 2014: Cochrane
      Skin Group Specialised Register, CENTRAL (2014, Issue 5), MEDLINE(from 1946),
      EMBASE (from 1974) and PsycINFO (from 1806). We searched five trials registers
      and checked articles for references to relevant randomised controlled
      trials.Selection criteria We included randomised controlled trials of H1
      antihistamines for CSU. Interventions included single therapy or a combination of
      H1-antihistamines compared with no treatment (placebo) or another active
      pharmacological compound at any dose.Data collection and analysis We used
      standard methodological procedures as expected by The Cochrane Collaboration.Our
      primary outcome measures were proportion of participants with complete
      suppression of urticaria: 'good or excellent' response,50% or greater improvement
      in quality of life measures, and adverse events.We present risk ratios (RR) with
      95% confidence intervals(CIs). Main results We identified 73 studies (9759
      participants); 34 studies provided data for 23 comparisons. The duration of the
      intervention was up to two weeks (short-term) or longer than two weeks and up to
      three months (intermediate-term).Cetirizine 10mg once daily in the short term and
      in the intermediate term led to complete suppression of urticaria by more
      participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91). For this
      same outcome, comparison of desloratadine versus placebo in the intermediate term
      (5 mg) (RR 37.00, 95% CI 2.31 to 593.70) and in the short term (20 mg) (RR 15.97,
      95% CI 1.04 to 245.04)favoured desloratadine, but no differences were seen
      between 5 mg and 10 mg for short-term treatment.Levocetirizine 20 mg per day
      (short-term) was more effective for complete suppression of urticaria compared
      with placebo (RR 20.87,95% CI 1.37 to 317.60), and at 5 mg was effective in the
      intermediate term (RR 52.88, 95% CI 3.31 to 843.81) but not in the shortterm, nor
      was 10 mg effective in the short term.Rupatadine at 10 mg and 20 mg in the
      intermediate term achieved a 'good or excellent response' compared with placebo
      (RR 1.35,95% CI 1.03 to 1.77).Loratadine (10 mg) versus placebo (RR 1.86, 95% CI
      0.91 to 3.79) and loratadine (10 mg) versus cetirizine (10 mg) (RR 1.05, 95%CI
      0.76 to 1.43) over short-term and intermediate-term treatment showed no
      significant difference for 'good or excellent response' or for complete
      suppression of urticaria, respectively.Loratadine (10 mg) versus desloratadine (5
      mg) (intermediate-term) showed no statistically significant difference for
      complete suppression of urticaria (RR 0.91, 95% CI 0.78 to 1.06) or for 'good or
      excellent response' (RR 1.04, 95% CI 0.64 to 1.71). For loratadine(10 mg) versus
      mizolastine (10 mg) (intermediate-term), no statistically significant difference
      was seen for complete suppression of urticaria (RR 0.86, 95% CI 0.64 to 1.16) or
      for 'good or excellent response' (RR 0.88, 95% CI 0.55 to 1.42).Loratadine (10mg)
      versus emedastine (2mg) (intermediate-term) showed no statistically significant
      difference for complete suppression(RR 1.04, 95% CI 0.78 to 1.39) or for 'good or
      excellent response' (RR 1.09, 95% CI 0.96 to 1.24); the quality of the evidence
      was moderate for this comparison.No difference in short-term treatment was noted
      between loratadine (10mg) and hydroxyzine (25mg) in terms of complete
      suppression(RR 1.00, 95% CI 0.32 to 3.10).When desloratadine (5 to 20 mg) was
      compared with levocetirizine (5 to 20 mg), levocetirizine appeared to be the more
      effective (P value < 0.02).In a comparison of fexofenadine versus cetirizine,
      more participants in the cetirizine group showed complete suppression of
      urticaria(P value < 0.001).Adverse events leading to withdrawals were not
      significantly different in the following comparisons: cetirizine versus placebo
      at 10 mg and 20 mg (RR 3.00, 95% CI 0.68 to 13.22); desloratadine 5 mg versus
      placebo (RR 1.46, 95% CI 0.42 to 5.10); loratadine 10 mg versus mizolastine 10 mg
      (RR 0.38, 95% CI 0.04 to 3.60); loratadine 10mg versus emedastine 2mg (RR 1.09,
      95%CI 0.07 to 17.14);cetirizine 10 mg versus hydroxyzine 25 mg (RR 0.78, 95% CI
      0.25 to 2.45); and hydroxyzine 25 mg versus placebo (RR 3.64, 95%CI 0.77 to
      17.23), all intermediate term.No difference was seen between loratadine 10 mg
      versus mizolastine 10 mg in the proportion of participants with at least
      50%improvement in quality of life (RR 3.21, 95% CI 0.32 to 32.33).Authors'
      conclusions Although the results of our review indicate that at standard doses of
      treatment, several antihistamines are effective when compared with placebo, all
      results were gathered from a few studies or, in some cases, from single-study
      estimates. The quality of the evidence was affected by the small number of
      studies in each comparison and the small sample size for many of the outcomes,
      prompting us to downgrade the quality of evidence for imprecision (unless stated
      for each comparison, the quality of the evidence was low).No single H1
      antihistamine stands out as most effective. Cetirizine at 10 mg once daily in the
      short term and in the intermediate term was found to be effective in completely
      suppressing urticaria. Evidence is limited for desloratadine given at 5 mg once
      daily in the intermediate term and at 20 mg in the short term. Levocetirizine at
      5 mg in the intermediate but not short term was effective for complete
      suppression. Levocetirizine 20 mg was effective in the short term, but 10 mg was
      not. No difference in rates of withdrawal due to adverse events was noted between
      active and placebo groups. Evidence for improvement in quality of life was
      insufficient.

PMID- 25397903
TI  - Non-invasive clinical parameters for the prediction of urodynamic bladder outlet
      obstruction: analysis using causal Bayesian networks.
AB  - PURPOSE: To identify non-invasive clinical parameters to predict urodynamic
      bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia
      (BPH) using causal Bayesian networks (CBN). SUBJECTS AND METHODS: From October
      2004 to August 2013, 1,381 eligible BPH patients with complete data were selected
      for analysis. The following clinical variables were considered: age, total
      prostate volume (TPV), transition zone volume (TZV), prostate specific antigen
      (PSA), maximum flow rate (Qmax), and post-void residual volume (PVR) on
      uroflowmetry, and International Prostate Symptom Score (IPSS). Among these
      variables, the independent predictors of BOO were selected using the CBN model.
      The predictive performance of the CBN model using the selected variables was
      verified through a logistic regression (LR) model with the same dataset. RESULTS:
      Mean age, TPV, and IPSS were 6.2 (+/-7.3, SD) years, 48.5 (+/-25.9) ml, and 17.9
      (+/-7.9), respectively. The mean BOO index was 35.1 (+/-25.2) and 477 patients
      (34.5%) had urodynamic BOO (BOO index >=40). By using the CBN model, we
      identified TPV, Qmax, and PVR as independent predictors of BOO. With these three
      variables, the BOO prediction accuracy was 73.5%. The LR model showed a similar
      accuracy (77.0%). However, the area under the receiver operating characteristic
      curve of the CBN model was statistically smaller than that of the LR model (0.772
      vs. 0.798, p = 0.020). CONCLUSIONS: Our study demonstrated that TPV, Qmax, and
      PVR are independent predictors of urodynamic BOO.

PMID- 25397905
TI  - Functionalization of Krebs-type polyoxometalates with N,O-chelating ligands: a
      systematic study.
AB  - The first organic derivatives of 3d-metal-disubstituted Krebs-type
      polyoxometalates have been synthesized under mild bench conditions via
      straightforward replacement of labile aqua ligands with N,O-chelating planar
      anions on either preformed or in situ-generated precursors. Nine hybrid clusters
      containing carboxylate derivatives of five- or six-membered aromatic N
      heterocycles as antenna ligands have been obtained as pure crystalline phases and
      characterized by elemental and thermal analyses, infrared spectroscopy, and
      single-crystal X-ray diffraction. They all show the general formula
      [{M(II)L(H2O)}2(WO2)2(B-beta-XW9O33)2](n-) and can be classified as follows: 1
      SbM, where L = 1H-imidazole-4-carboxylate (imc), X = Sb(III), n = 12, and M(II) =
      Mn, Co, Ni, Zn; 1-TeM, where L = imc, X = Te(IV), n = 10, and M(II) = Mn, Co; 2
      SbNi, where L = 1H-pyrazole-3-carboxylate (pzc), X = Sb(III), n = 12, and M(II) =
      Ni; and 3-SbM, where L = pyrazine-2-carboxylate (pyzc), X =Sb(III), n = 12, and
      M(II) = Co, Zn. The 3d-metal-disubstituted tungstotellurate(IV) skeleton of
      compounds 1-TeM is unprecedented in polyoxometalate chemistry. The stability of
      these hybrid Krebs-type species in aqueous solution has been confirmed by (1)H
      NMR spectroscopy performed on the diamagnetic 1-SbZn and 3-SbZn derivatives. Our
      systematic study of the reactivity of disubtituted Krebs-type polyoxotungstates
      toward diazole-, pyridine-, and diazinecarboxylates demonstrates that organic
      derivatization is strongly dependent on the nature of the ligand, as follows: imc
      displays a "universal ligand" character, as functionalization takes place
      regardless of the external 3d metal and heteroatom; pzc and pyzc show selectivity
      toward specific 3d metals; pyridazine-3-carboxylate and pyrimidine-4-carboxylate
      promote partial decomposition of specific precursors, leading to [M(II)L2(H2O)2]
      complexes; and picolinate is inert under all conditions tested. 

PMID- 25397906
TI  - Resonance energy transfer in DNA duplexes labeled with localized dyes.
AB  - The growing maturity of DNA-based architectures has raised considerable interest
      in applying them to create photoactive light harvesting and sensing devices.
      Toward optimizing efficiency in such structures, resonant energy transfer was
      systematically examined in a series of dye-labeled DNA duplexes where donor
      acceptor separation was incrementally changed from 0 to 16 base pairs. Cyanine
      dyes were localized on the DNA using double phosphoramidite attachment chemistry.
      Steady state spectroscopy, single-pair fluorescence, time-resolved fluorescence,
      and ultrafast two-color pump-probe methods were utilized to examine the energy
      transfer processes. Energy transfer rates were found to be more sensitive to the
      distance between the Cy3 donor and Cy5 acceptor dye molecules than efficiency
      measurements. Picosecond energy transfer and near-unity efficiencies were
      observed for the closest separations. Comparison between our measurements and the
      predictions of Forster theory based on structural modeling of the dye-labeled DNA
      duplex suggest that the double phosphoramidite linkage leads to a distribution of
      intercalated and nonintercalated dye orientations. Deviations from the
      predictions of Forster theory point to a failure of the point dipole
      approximation for separations of less than 10 base pairs. Interactions between
      the dyes that alter their optical properties and violate the weak-coupling
      assumption of Forster theory were observed for separations of less than four base
      pairs, suggesting the removal of nucleobases causes DNA deformation and leads to
      enhanced dye-dye interaction. 

PMID- 25397907
TI  - Serial in vivo imaging using a fluorescence probe allows identification of tumor
      early response to cetuximab immunotherapy.
AB  - Cetuximab is an antiepidermal growth factor receptor (EGFR) monoclonal antibody
      that has received the approval of the Food and Drug Administration (FDA) for
      cancer treatment. However, most clinical studies indicate that cetuximab can only
      elicit positive effects on a subset of cancer patients. In this study, we
      investigated whether near-infrared fluorescence (NIRF) imaging of tumor vascular
      endothelial growth factor (VEGF) expression could be a biomarker for tumor early
      response to cetuximab therapy in preclinical wild-type and mutant tumor models of
      the KRAS gene. The treatment efficacy of cetuximab was determined in both HT-29
      (wild-type KRAS) and HTC-116 (mutant KRAS) human colon cancer models. A VEGF
      specific optical imaging probe (Dye755-Ran) was synthesized by conjugating
      ranibizumab (an anti-VEGF antibody Fab fragment) with a NIRF dye. Serial optical
      scans with Dye755-Ran were performed in HT-29 and HTC-116 xenograft models. By
      using longitudinal NIRF imaging, we were able to detect early tumor response on
      day 3 and day 5 after initiation of cetuximab treatment in the cetuximab
      responsive HT-29 tumor model. Enzyme-linked immunosorbent assay (ELISA) confirmed
      that cetuximab treatment inhibited human VEGF expression in the KRAS wild-type HT
      29 tumor but not in the KRAS mutant HCT-116 tumor. We have demonstrated that the
      antitumor effect of cetuximab can be noninvasively monitored by serial
      fluorescence imaging using Dye755-Ran. VEGF expression detected by optical
      imaging could serve as a sensitive biomarker for tumor early response to drugs
      that directly or indirectly act on VEGF. 

PMID- 25397908
TI  - [Evaluation of Specialised Paediatric Palliative Home Care in Lower Saxony,
      Germany - A Qualitative Study on Parents' Perspectives].
AB  - BACKGROUND: In 2007 the children's right to specialised paediatric palliative
      home care became law in Germany. This claim should be met in Lower Saxony by the
      establishment of a comprehensive specialised paediatric home care (SPPHC). Since
      April 2010, a central office undertakes the coordination and administration
      throughout the federal state. Regional teams comprising nursing, medical and
      psychosocial specialists care for the children and adolescents suffering from
      complex conditions due to life-limiting conditions - subsidiary to regional
      health care providers. The aim of the study was to evaluate SPPHC in Lower
      Saxony. METHODOLOGY: From June 2012 to February 2013, semi-structured interviews
      were conducted with 20 parents of children aged from 3 to 18 years. The young
      patients fulfilled all criteria to be eligible for SPPHC. 13 of the families
      experienced SPPHC. 7 families did not utilise the specialised care, mostly
      because the palliative situation occurred before the implementation of
      specialised care. Data were analysed using content analysis (Mayring). Therefore,
      key aspects of paediatric palliative home care were summarised in main
      categories. The evaluation of parent's satisfaction with palliative home care was
      performed by an evaluation scheme developed for the main categories (very good -
      good - bad- very bad) and operated for every case. RESULTS: 6 dimensions of
      paediatric palliative home care were identified: (i) benefit of care, (ii)
      continuity of care, (iii) perception of care providers as a team, (iv) dealing
      with the issues death and dying/hospice and palliative, (v) care provider's
      communication/cooperation with parents, and (vi) parent's Information. As all
      parents clearly indicated a rating on the first 3 categories, these categories
      were selected for the evaluation of parent's satisfaction with the received home
      care. The evaluation revealed that parents experienced in SPPHC looked upon these
      3 main categories more favourably than parents without the experience of SPPHC.
      As room for improvement, the respondents requested the extension of physician's
      presence and communication with the families as well as with each other, efforts
      to better meet the needs of psycho-social support of the families and to optimise
      follow up-care. CONCLUSION: The implementation of SAPPV was rated positively by
      the concerned families. In addition, options for improvement could be identified.

PMID- 25397909
TI  - [The significance of a large number of health insurance funds and fusions for
      health services research with statutory health insurance data in Germany -
      experiences of the lidA study].
AB  - Since 1970 the health insurance system in Germany has shrunk by more than 90% to
      132 statutory health insurance funds (SHI) at present. For studies using data
      from different SHI, this development means a reduction of contacts and a higher
      workload when requesting data. The latter is due to the fact that fusions bind
      resources in the health insurance funds. In order to avoid selection in studies
      among the insured, all SHI must be contacted. Additionally, 15 controlling
      institutions on the state and national level have to agree as determined in S 75
      of the German Social Code number 10. The lidA study - a German cohort study on
      work, age and health intends to link primary and secondary data from all SHI of
      those insured who have given their agreement for participation. Since the
      beginning of the study in 2009 the number of SHI has been reduced by 70. Of the 6
      585 interviews in 2011 approximately half of the interviewees agreed in written
      form that their individual health insurance data can be linked. This portion of
      the insured is dispersed among 95 SHI. At this point, 11 contracts with SHI are
      realised (approximately 50% of the insured) and 8 data controlling authorities
      have been contacted. The problems involved in the fusion of SHI and its meaning
      for research are explained in this article. The fusion of SHI makes sense for the
      long term. It will lead to a reduction of contacts and contracts that researchers
      have to establish in order to analyse the data. Therefore, this article also
      discusses the alternative of creating a meta-data set of all the data from the
      different SHI combined. 

PMID- 25397910
TI  - [Clinical reasoning supportive to a medical service provider as a tool for
      complaint management: a case study for pragmatic reasoning].
AB  - The process of "clinical reasoning" is exemplified as supportive to the complaint
      management of the Statutory Medical Health Advisory Board in Lower Saxony,
      Germany, within the operational division for long-term care insurance. A model
      case from real life illustrates in detail the hypothetical-deductive approach by
      Beusheusen and Klemme/Siegmann. Because of the potential area of conflicts
      between human concern in the case of a long-term care burden and legal
      requirements, the process was analysed in terms of a pragmatic reasoning. Human
      resources of the claimant and persons in charge at customer's service were
      demonstrated as well as political, statutory and institutional determining
      factors. Concluding self-perception validates the process in the context of
      evidence-based practice. 

PMID- 25397911
TI  - GATA2 deficiency.
AB  - PURPOSE OF REVIEW: GATA2 deficiency is a germline disease that causes a wide
      spectrum of phenotypes including viral and bacterial infections, cytopenias,
      myelodysplasia, myeloid leukemias, pulmonary alveolar proteinosis and lymphedema.
      The age of clinical presentation ranges from early childhood to late adulthood,
      with most occurring in adolescence to early adulthood. We review the expanding
      GATA2-deficient phenotype, molecular genetics of disease and developments in
      treatment. RECENT FINDINGS: GATA2 mutations have been found in up to 10% of those
      with congenital neutropenia and/or aplastic anemia. Heterozygous mutations appear
      to cause haploinsufficiency due to either protein dysfunction or uniallelic
      reduced transcription. Disease-associated mutations in intronic regulatory
      elements or variations within the 5' leader exons indicate that regulation of
      GATA2 is critical. Those with GATA2 mutations are at high risk for
      myelodysplasia, cytogenetic abnormalities, acute myeloid leukemia or chronic
      myelomonocytic leukemia. Bone marrow transplantation has been successful for both
      hematopoietic and pulmonary alveolar proteinosis repair. SUMMARY: GATA2 is a zinc
      finger transcription factor essential for embryonic and definitive hematopoiesis
      as well as lymphatic angiogenesis. GATA2 deficiency is caused by a variety of
      mutations in the GATA2 gene and can have variable presentation, onset and
      outcome. Patients are susceptible to mycobacterial, viral and fungal infections
      and can develop myelodysplasia, acute or chronic leukemias, lymphedema and
      pulmonary alveolar proteinosis. Hematopoietic stem cell transplantation reverses
      most of the clinical phenotype with good long-term outcomes.

PMID- 25397912
TI  - Equivalent pathways in melting and gelation of well-defined biopolymer networks.
AB  - We use multiple particle tracking microrheology to study the melting and gelation
      behavior of well-defined collagen-inspired designer biopolymers expressed by the
      transgenic yeast P. Pastoris. The system consists of a hydrophilic random coil
      like middle block and collagen-like end block. Upon cooling, the end blocks
      assemble into well-defined transient nodes with exclusively 3-fold functionality.
      We apply the method of time-cure superposition of the mean-square displacement of
      tracer beads embedded in the biopolymer matrix to study the kinetics and
      thermodynamics of approaching the gel point from both the liquid and the solid
      side. The melting point, gel point, and critical relaxation exponents are
      determined from the shift factors of the mean-square displacement and we discuss
      the use of dynamic scaling exponents to correctly determine the critical
      transition. Critical relaxation exponents obtained for different concentrations
      in both systems are compared with the currently existing dynamic models in
      literature. In our study, we find that, while the time scales of gelation and
      melting are different by orders of magnitude, and show inverse dependence on
      concentration, that the pathways followed are completely equivalent. 

PMID- 25397913
TI  - The puzzle and challenge in treating hepatolithiasis.

PMID- 25397914
TI  - Infrared spectra of HCl(H2O)n clusters from semiempirical Born-Oppenheimer
      molecular dynamics simulations.
AB  - Infrared spectra of HCl(H2O)n clusters, with n = 4-10 and 21, are calculated at T
      = 50 K from semiempirical Born-Oppenheimer molecular dynamics simulations
      performed with the PM3-MAIS model. The specific focus of this study is on the
      relationship between spectroscopic features associated with the presence of the
      excess proton generated by the HCl dissociation as a function of n and the
      underlying water hydrogen-bonding topologies. Vibrational modes involving the
      motion of the excess proton are attributed to specific features appearing at
      ~1175 cm(-1) for Zundel-type structures, in the 1670-1800 cm(-1) range for
      intermediate Zundel-Eigen-type structures, and at ~2820 cm(-1) for Eigen-type
      structures. This broad range of vibrational frequencies correlates with the
      position of the excess proton within the clusters. Overall, the theoretical
      predictions are in good agreement with the available experimental data. 

PMID- 25397915
TI  - Tandem synthesis of 3-halo-5-substituted isoxazoles from 1-copper(I) alkynes and
      dihaloformaldoximes.
AB  - A tandem synthesis of 3-halo-5-substituted isoxazoles has been developed from 1
      copper(I) alkynes and dihaloformaldoximes under base-free conditions. Thus, 1,3
      dipolar cycloaddition and all its drawbacks can now be avoided completely. 

PMID- 25397916
TI  - Lanthanide-doped upconversion materials: emerging applications for photovoltaics
      and photocatalysis.
AB  - Photovoltaics and photocatalysis are two significant applications of clean and
      sustainable solar energy, albeit constrained by their inability to harvest the
      infrared spectrum of solar radiation. Lanthanide-doped materials are particularly
      promising in this regard, with tunable absorption in the infrared region and the
      ability to convert the long-wavelength excitation into shorter-wavelength light
      output through an upconversion process. In this review, we highlight the emerging
      applications of lanthanide-doped upconversion materials in the areas of
      photovoltaics and photocatalysis. We attempt to elucidate the fundamental
      physical principles that govern the energy conversion by the upconversion
      materials. In addition, we intend to draw attention to recent technologies in
      upconversion nanomaterials integrated with photovoltaic and photocatalytic
      devices. This review also provides a useful guide to materials synthesis and
      optoelectronic device fabrication based on lanthanide-doped upconversion
      materials. 

PMID- 25397917
TI  - Cucurbit[6]uril-based supramolecular assemblies: possible application in
      radioactive cesium cation capture.
AB  - Multidimensional supramolecular assemblies based on cucurbit[n]uril (n = 6 or 7)
      were constructed via the outer-surface interactions of cucurbit[n]urils with the
      polyaromatic compound 4,4',4"-benzene-1,3,5-triyl-tribenzoate as a structure
      directing agent. Most impressively, the cucurbit[6]uril-based assembly exhibits
      high selectivity for capture of cesium cations among the common alkali metal ions
      in a basic medium and releases the cesium cations under acidic conditions. This
      reversible process enables possible applications in cesium cation capture. 

PMID- 25397918
TI  - Synthesis of a Cu2+-selective probe derived from rhodamine and its application in
      cell imaging.
AB  - A new fluorescent probe P based on rhodamine for Cu2+ was synthesized and
      characterized. The new probe P showed high selectivity to Cu2+ over other tested
      metal ions. With optimal conditions, the proposed probe P worked in a wide linear
      range of 1.0 * 10(-6)-1.0 * 10(-5) M with a detection limit of 3.3 * 10(-7) M
      Cu2+ in ethanol-water solution (9:1, v:v, 20 mM HEPES, pH 7.0). Furthermore, it
      has been used for imaging of Cu2+ in living cells with satisfying results.

PMID- 25397919
TI  - An algorithm for retrieving land surface temperatures using VIIRS data in
      combination with multi-sensors.
AB  - A practical algorithm was proposed to retrieve land surface temperature (LST)
      from Visible Infrared Imager Radiometer Suite (VIIRS) data in mid-latitude
      regions. The key parameter transmittance is generally computed from water vapor
      content, while water vapor channel is absent in VIIRS data. In order to overcome
      this shortcoming, the water vapor content was obtained from Moderate Resolution
      Imaging Spectroradiometer (MODIS) data in this study. The analyses on the
      estimation errors of vapor content and emissivity indicate that when the water
      vapor errors are within the range of +/-0.5 , the mean retrieval error of the
      present algorithm is 0.634 K; while the land surface emissivity errors range from
      -0.005 to +0.005, the mean retrieval error is less than 1.0 K. Validation with
      the standard atmospheric simulation shows the average LST retrieval error for the
      twenty-three land types is 0.734 K, with a standard deviation value of 0.575 K.
      The comparison between the ground station LST data indicates the retrieval mean
      accuracy is -0.395 K, and the standard deviation value is 1.490 K in the regions
      with vegetation and water cover. Besides, the retrieval results of the test data
      have also been compared with the results measured by the National Oceanic and
      Atmospheric Administration (NOAA) VIIRS LST products, and the results indicate
      that 82.63% of the difference values are within the range of -1 to 1 K, and
      17.37% of the difference values are within the range of +/-2 to +/-1 K. In a
      conclusion, with the advantages of multi-sensors taken fully exploited, more
      accurate results can be achieved in the retrieval of land surface temperature. 

PMID- 25397921
TI  - The cup anemometer, a fundamental meteorological instrument for the wind energy
      industry. Research at the IDR/UPM Institute.
AB  - The results of several research campaigns investigating cup anemometer
      performance carried out since 2008 at the IDR/UPM Institute are included in the
      present paper. Several analysis of large series of calibrations were done by
      studying the effect of the rotor's geometry, climatic conditions during
      calibration, and anemometers' ageing. More specific testing campaigns were done
      regarding the cup anemometer rotor aerodynamics, and the anemometer signals. The
      effect of the rotor's geometry on the cup anemometer transfer function has been
      investigated experimentally and analytically. The analysis of the anemometer's
      output signal as a way of monitoring the anemometer status is revealed as a
      promising procedure for detecting anomalies. 

PMID- 25397920
TI  - Using bio-functionalized magnetic nanoparticles and dynamic nuclear magnetic
      resonance to characterize the time-dependent spin-spin relaxation time for
      sensitive bio-detection.
AB  - In this work, we report the use of bio-functionalized magnetic nanoparticles
      (BMNs) and dynamic magnetic resonance (DMR) to characterize the time-dependent
      spin-spin relaxation time for sensitive bio-detection. The biomarkers are the
      human C-reactive protein (CRP) while the BMNs are the anti-CRP bound onto dextran
      coated Fe3O4 particles labeled as Fe3O4-antiCRP. It was found the time-dependent
      spin-spin relaxation time, T2, of protons decreases as time evolves.
      Additionally, the DeltaT2 of of protons in BMNs increases as the concentration of
      CRP increases. We attribute these to the formation of the magnetic clusters that
      deteriorate the field homogeneity of nearby protons. A sensitivity better than
      0.1 MUg/mL for assaying CRP is achieved, which is much higher than that required
      by the clinical criteria (0.5 mg/dL). The present MR-detection platform shows
      promise for further use in detecting tumors, viruses, and proteins. 

PMID- 25397922
TI  - Fear of negative evaluation moderates effects of social exclusion on selective
      attention to social signs.
AB  - Previous studies demonstrated that fear of negative evaluation (FNE) moderates
      responses to exclusion in late-stage social outcomes (e.g., social judgements and
      behaviours). People with low levels of FNE show affiliative responses, feeling
      compelled to recover their sense of belonging, whereas people with high levels of
      FNE do not. This study examined whether FNE also moderates responses to exclusion
      in early-stage interpersonal perception, manifested in selective attention. The
      experiment using a dot-probe task revealed that exclusion led participants with
      low levels of FNE to increase attention to signs of social acceptance (i.e.,
      smiling faces). It also revealed that exclusion led those with high levels of FNE
      to pay more attention to signs of social threat (i.e., angry faces) relative to
      those of social acceptance. Thus, exclusion makes the motivation to protect
      oneself from social threats dominant over the motivation to reestablish social
      bonds among those who fear negative evaluation. 

PMID- 25397923
TI  - Characterization of hypothetical protein VNG0128C from Halobacterium NRC-1
      reveals GALE like activity and its involvement in Leloir pathway of galactose
      metabolism.
AB  - VNG0128C, a hypothetical protein from Halobacterium NRC-1, was chosen for
      detailed insilico and experimental investigations. Computational exercises
      revealed that VNG0128C functions as NAD(+) binding protein. The phylogenetic
      analysis with the homolog sequences of VNG0128C suggested that it could act as
      UDP-galactose 4-epimerase. Hence, the VNG0128C sequence was modeled using a
      suitable template and docking studies were performed with NAD and UDP-galactose
      as ligands. The binding interactions strongly indicate that VNG0128C could
      plausibly act as UDP-galactose 4-epimerase. In order to validate these insilico
      results, VNG0128C was cloned in pUC57, subcloned in pET22b(+), expressed in BL21
      cells and purified using nickel affinity chromatography. An assay using blue
      dextran was performed to confirm the presence of NAD binding domain. To
      corroborate the epimerase like enzymatic role of the hypothetical protein, i.e.
      the ability of the enzyme to convert UDP-galactose to UDP-glucose, the conversion
      of NAD to NADH was measured. The experimental assay significantly correlated with
      the insilico predictions, indicating that VNG0128C has a NAD(+) binding domain
      with epimerase activity. Consequently, its key role in nucleotide-sugar
      metabolism was thus established. Additionally, the work highlights the need for a
      methodical characterization of hypothetical proteins (less studied class of
      biopolymers) to exploit them for relevant applications in the field of biology. 

PMID- 25397924
TI  - Corneal Anterior Power Calculation for an IOL in Post-PRK Patients.
AB  - PURPOSE: After corneal refractive surgery, there is an overestimation of the
      corneal power with the devices routinely used to measure it. Therefore, the
      objective of this study was to determine whether, in patients who underwent
      photorefractive keratectomy (PRK), it is possible to predict the earlier
      preoperative anterior corneal power from the postoperative (PO) posterior corneal
      power. A comparison is made using a formula published by Saiki for laser in situ
      keratomileusis patients and a new one calculated specifically from PRK patients.
      METHODS: The Saiki formula was tested in 98 eyes of 98 patients (47 women) who
      underwent PRK for myopia or myopic astigmatism. Moreover, anterior and posterior
      mean keratometry (Km) values from a Scheimpflug camera were measured to obtain a
      specific regression formula. RESULTS: The mean (+/-SD) preoperative Km was 43.50
      (+/-1.39) diopters (D) (range, 39.25 to 47.05 D). The mean (+/-SD) Km value
      calculated with the Saiki formula using the 6 months PO posterior Km was 42.94
      (+/-1.19) D (range, 40.34 to 45.98 D) with a statistically significant difference
      (p < 0.001). Six months after PRK in our patients, the posterior Km was
      correlated with the anterior preoperative one by the following regression
      formula: y = -4.9707x + 12.457 (R2 = 0.7656), where x is PO posterior Km and y is
      preoperative anterior Km, similar to the one calculated by Saiki. CONCLUSIONS:
      Care should be taken in using the Saiki formula to calculate the preoperative Km
      in patients who underwent PRK.

PMID- 25397925
TI  - Inflammation and keratoconus.
AB  - Keratoconus (KC) has been traditionally classified as a noninflammatory disease.
      Barring loss of function, the other classic signs of inflammation (heat, redness,
      swelling, pain) are not usually obvious or even apparent in KC. This clinical
      perspective examines the evidence and implications of numerous inflammatory
      processes that have been recognized in the tears of KC patients as well as some
      inflammation relevant differences found in the KC cornea. The roles of
      inflammation in corneal trauma attributed to eye rubbing and/or contact lens wear
      are examined as is the significance of atopy, allergic disease, dry eye disease,
      degradative enzyme activity, wound healing, reduced anti-inflammatory capacity,
      and ultraviolet irradiation. It is possible that any comorbidity that is
      inflammatory in nature may add synergistically to other forms of KC-related
      inflammation and exacerbate its pathogenetic processes. For example, some
      features of inflammation in ocular rosacea and associated corneal thinning and
      distortion could have some possible relevance to KC. An analogy is drawn with
      osteoarthritis, which also involves significant inflammatory processes but, like
      KC, does not meet all the classic criteria for an inflammatory disease.
      Classifying KC as quasi-inflammatory (inflammatory-related) rather than a
      noninflammatory disease appears to be more appropriate and may help focus
      attention on the possibility of developing effective anti-inflammatory therapies
      for its management. 

PMID- 25397926
TI  - Small-incision lenticule extraction for myopia: results of a 12-month prospective
      study.
AB  - PURPOSE: To analyze the safety, efficacy, stability, and predictability of small
      incision lenticule extraction to correct myopia. METHODS: Patients were evaluated
      preoperatively and then at 1 day, at 2 weeks, and at 1, 3, 6, and 12 months
      postoperatively. Safety, efficacy, stability, predictability, and surgical
      complications were assessed. Changes in higher-order aberrations, intraocular
      pressure, central corneal thickness, dry eye signs, contrast sensitivity, and
      subjective glare symptoms were evaluated. RESULTS: All 52 myopic patients in the
      initial treatment group completed the final 12-month follow-up. At 12 months,
      90.4% of eyes were within +/-0.5 diopters (D) of the intended refractive target.
      The mean (+/-SD) change in manifest refraction from 1 day to 12 months was -0.06
      (+/-0.37) D. The uncorrected visual acuity was better than or equal to 20/20 in
      83% of eyes; 98% of eyes had a best-corrected visual acuity of better than or
      equal to 20/20. No eye lost two or more Snellen lines. There was an increase in
      higher-order aberrations, spherical aberration, and coma postoperatively. No
      significant increase in intraocular pressure occurred. The tear breakup time
      decreased significantly after surgery and did not return to preoperative levels
      within 12 months. The log contrast sensitivity value with glare of 6.3, 4.0, 2.5,
      and 1.6 degrees of visual angle at 1 month was statistically significantly
      reduced but recovered to preoperative levels after 3 months. Twenty-seven percent
      of patients complained of mild or moderate glare postoperatively, but the
      symptoms disappeared during the 12-month follow-up period with no influence on
      daily life. No vision-threatening complications occurred. CONCLUSION: Small
      incision lenticule extraction is a promising corneal refractive procedure to
      correct myopia.

PMID- 25397927
TI  - Multimodality imaging in diagnosing polypoidal choroidal vasculopathy.
AB  - PURPOSE: Report a case of polypoidal choroidal vasculopathy (PCV) and reveal its
      characteristics in multispectral imaging (MSI), a novel modality that examines
      individual retinal layers and enhances visualization of deep retinal structures.
      CASE REPORT: A 60-year-old Chinese woman presented with blurred vision in her
      left eye for over 1 week. Fundus examination revealed massive subretinal
      hemorrhage in the posterior pole with reddish orange polyp-like structure on the
      fovea of the left eye. Optical coherence tomography showed classic
      hyperreflectivity in the choroidal layer, known as the "double-layer" sign,
      adjacent to a serous retinal pigment epithelial detachment, which was further
      confirmed in fluorescein angiography of the left eye. Indocyanine green
      angiography demonstrated the features of PCV, including multiple polyps arising
      out of inner choroidal vessels in the early phase as hyperfluorescent spots and
      ringlike silhouette staining of the polyps in the late phase. Multispectral
      imaging as a new modality was introduced to visualize the polypoidal lesion as a
      polyp-like cluster of hyperreflectance in the short-wavelength images (green and
      yellow) with subsequent highly defined ringlike hyperreflectance in the longer
      wavelength images (near-infrared and infrared). According to the manifestations
      above, this patient's final diagnosis was PCV in the left eye. CONCLUSIONS: This
      is the first report using MSI as a novel imaging modality for the detection of
      PCV. Multispectral imaging can reveal highly defined hyperreflective polyp-like
      structures in the longer-wavelength images, which is compatible with the
      indocyanine green angiography findings, indicating preliminarily the advantages
      of noninvasiveness, simplicity, and effectiveness of MSI in diagnosing PCV.

PMID- 25397928
TI  - Gene therapy for hemophilia: the clot thickens.

PMID- 25397932
TI  - A systematic focus on occupational therapy education.

PMID- 25397929
TI  - Our journey to successful gene therapy for hemophilia B.

PMID- 25397933
TI  - Examining occupational therapy education through faculty engagement in curriculum
      mapping and pedagogical reflection.
AB  - This article discusses a 1-yr evaluation study of a master of science in
      occupational therapy program to examine curriculum content and pedagogical
      practices as a way to gauge program preparedness to move to a clinical doctorate.
      Faculty members participated in a multitiered qualitative study that included
      curriculum mapping, semistructured individual interviewing, and iterative group
      analysis. Findings indicate that curriculum mapping and authentic dialogue helped
      the program formulate a more streamlined and integrated curriculum with increased
      faculty collaboration. Curriculum mapping and collaborative pedagogical
      reflection are valuable evaluation strategies for examining preparedness to offer
      a clinical doctorate, enhancing a self-study process, and providing information
      for ongoing formative curriculum review. 

PMID- 25397934
TI  - Interprofessional evidence-based clinical scholar program: learning to work
      together.
AB  - St. Catherine University and North Memorial Medical Center conducted an
      Interprofessional Clinical Scholar Program (ICSP) involving five teams of staff,
      students, and faculty. The aim of the case study was to determine how the
      interprofessional teams implemented evidence-based projects. We triangulated data
      from interviews, field notes, and surveys to produce themes: learning to value
      interprofessional teams, working as a team, and being evidence-based
      practitioners. We found significant differences pre- and post-ICSP on the
      Attitudes Toward Interprofessional Teamwork and Education scale, t(14) = -5.48, p
      < .005, and the Terminology subscale of the Evidence-Based Practice Profile,
      t(15) = -4.04, p = .001. We found no change in scores on the Evidence-Based
      Practice Belief Scale, t(14) = -1.49, p = .156. The study supported predicted
      patterns of benefits from ICSP. Not all participants benefited because of
      variability in attendance. 

PMID- 25397935
TI  - Epistemic and ontological cognition of entering and postdidactic occupational
      therapy students.
AB  - Beliefs about knowledge and knowing, also called epistemic and ontological
      cognition (EOC), are associated with many aspects of learning and achievement; no
      published studies have described the EOC of occupational therapy students. This
      study compares and contrasts occupational therapy students' EOC at entry and on
      completion of didactic coursework. Twenty-one incoming and 33 postdidactic
      students completed the Epistemic Beliefs Inventory and the modified Four-Quadrant
      Scale and provided explanations for their self-ratings. Results indicate that the
      postdidactic students held more sophisticated stances toward occupational therapy
      specific knowledge. The entering students demonstrated dogmatist and skeptic
      perspectives, with minimal evidence of a rationalist view of knowledge, whereas
      the postdidactic students showed evidence of primarily skeptic stances, with the
      emergence of rationalist views. Implications for occupational therapy theory,
      education, and research are discussed. 

PMID- 25397936
TI  - Use of simulation in occupational therapy education: way of the future?
AB  - OBJECTIVE. A national study explored the use of simulated learning experiences in
      U.S. occupational therapy and occupational therapy assistant entry-level academic
      programs. METHOD. Program faculty at 245 of 310 occupational therapy assistant
      and occupational therapy entry-level programs completed a self-reported 23
      question online survey on the use of simulation and its challenges and benefits.
      Data were analyzed using frequency, percentage, and thematic coding. RESULTS. Of
      245 programs, 175 (71%) reported using simulation, with the most common teaching
      methods incorporating human actors and students and video cases. Simulated
      scenarios were primarily presented in intervention courses (90%). Faculty
      provided feedback that benefits of the simulated experience were increased
      critical reasoning, problem solving and decision making, and communication among
      students. Challenges were time, cost, and scheduling. CONCLUSION. Findings were
      similar to those in the literature in terms of simulated learning's uses,
      benefits, and challenges. Further research on student learning outcomes and
      pedagogy in occupational therapy is recommended. 

PMID- 25397937
TI  - Keynote address: searching for and identifying signature pedagogies in
      occupational therapy education.

PMID- 25397938
TI  - From collaboration to cause: breaking rural poverty cycles through educational
      partnerships.
AB  - The Missouri Health Professions Consortium (MHPC) Occupational Therapy Assistant
      Program is an innovative educational model that was specifically designed to
      address needs unique to rural communities. The model takes into account not only
      the distinctiveness of rural practice environments but also the educational
      barriers unique to rural student populations. The MHPC Occupational Therapy
      Assistant Program addresses the needs of these communities by providing
      educational opportunities to rural, place-bound students. The program has
      produced viable employment options, resulting in improved access to occupational
      therapy services as well as positive economic outcomes for graduates who reside
      in rural communities. 

PMID- 25397939
TI  - Comparison of on-campus and hybrid student outcomes in occupational therapy
      doctoral education.
AB  - We compared the graduate outcomes of doctoral students in a traditional on-campus
      occupational therapy program with those in a hybrid program. Participants were 81
      students from an on-campus program and 13 students from a hybrid program.
      Graduate outcomes were measured with student grade-point average (GPA) at the end
      of each academic year, cumulative GPA, Fieldwork Performance Exam, National Board
      for Certification in Occupational Therapy (NBCOT) practice exam scores, and final
      NBCOT pass rate. Consistent with previous research, our results revealed no
      significant differences on most outcome variables, suggesting that hybrid
      programs are an effective delivery model for postsecondary higher education.
      These findings may provide guidance to occupational therapy programs in
      curriculum design, content delivery, and program refinement and development.
      Replication of this study is needed with a larger sample and inclusion of
      qualitative data. Future studies should compare the affective domain of graduate
      outcomes in on-campus and online or hybrid programs. 

PMID- 25397940
TI  - Use of simulated patients and reflective video analysis to assess occupational
      therapy students' preparedness for fieldwork.
AB  - Educators must determine whether occupational therapy students are adequately
      prepared for Level II fieldwork once they have successfully completed the
      didactic portion of their coursework. Although studies have shown that students
      regard the use of video cameras and simulated patient encounters as useful tools
      for assessing professional and clinical behaviors, little has been published in
      the occupational therapy literature regarding the practical application of
      simulated patients or reflective video analysis. We describe a model for a final
      Comprehensive Practical Exam that uses both simulated patients and reflective
      video analysis to assess student preparedness for Level II fieldwork, and we
      report on student perceptions of these instructional modalities. We provide
      recommendations for designing, implementing, and evaluating simulated patient
      experiences in light of existing educational theory. 

PMID- 25397941
TI  - Use of Instructor-Produced YouTube(r) Videos to Supplement Manual Skills Training
      in Occupational Therapy Education.
AB  - An ongoing challenge to occupational therapy educators is how to provide
      resources and strategies that best assist students in learning, retaining, and
      replicating protocols in clinical manual assessment. This pilot survey study
      explored how 43 first-year master's of occupational therapy students enrolled in
      a kinesiology course perceived the value of implementing instructor-produced
      YouTube(r) videos of in-class assessment demonstrations. The videos, taken on a
      smartphone, were uploaded to a private YouTube URL created by the instructor and
      then linked to a pre-established Moodle learning platform. By the end of the 6-wk
      course, students had registered 2,573 views averaging 60 views per student.
      Postcourse mixed survey results revealed students perceived that the videos
      improved the quality of the course, increased their level of engagement and
      learning, and boosted confidence in their manual skills. Survey results also
      found that students correlated the instructor's willingness to develop online
      videos with a commitment to student learning. 

PMID- 25397942
TI  - Facilitated learning model to teach habits of evidence-based reasoning across an
      integrated master of science in occupational therapy curriculum.
AB  - We describe an integrated master of science in occupational therapy curriculum
      and a coordinated sequence of evidence-based practice (EBP) courses that
      incorporate systematic, pragmatic teaching strategies to develop students' EBP
      skills and habits of reasoning. The EBP courses focus sequentially on the
      occupational lives of clients and methods for gaining information about
      occupational performance and needs; appraising the internal, external, and
      statistical validity of intervention evidence; and generating evidence from one's
      own practice to answer questions about individual or group client outcomes. All
      EBP courses use facilitated learning processes that encourage graduate students
      to take responsibility for their own learning, guided by a carefully structured
      series of assignments. The integrated curriculum scaffolds the translation and
      application of previously learned knowledge and skills, including EBP knowledge,
      into different contexts. Student survey data suggest that graduating students
      view EBP as an integral part of the clinical process and begin to internalize the
      habits necessary to be evidence-based practitioners. 

PMID- 25397943
TI  - Occupational therapy education research agenda.

PMID- 25397944
TI  - Scholarship and research in occupational therapy education.
AB  - OBJECTIVE. The purpose of this study was to identify a baseline or benchmark for
      faculty engagement and productivity in occupational therapy education scholarship
      and research. METHOD. A custom-designed survey was emailed to 2,225 faculty
      members. The survey included questions on basic demographic information and
      education scholarship (e.g., use of evidence to inform teaching, frequency and
      nature of involvement in education scholarship. RESULTS. A total of 520 faculty
      members (23%) completed the survey. Of these, 450 (86.5%) identified themselves
      as full-time core faculty, and only their responses were analyzed. Although 90%
      of the faculty respondents engaged in scholarly teaching, only 34% identified
      education as an area of content expertise, and only 16% reported frequent
      involvement with education scholarship. Instructional methods were the primary
      area of study. CONCLUSION. A need exists to build research capacity for education
      research and more diversification of education research topics, including
      professional socialization and competencies. 

PMID- 25397945
TI  - Ferromagnetic resonance in epsilon-Co magnetic composites.
AB  - We investigate the electromagnetic properties of assemblies of nanoscale epsilon
      cobalt crystals with size range between 5 to 35 nm, embedded in a polystyrene
      matrix, at microwave (1-12 GHz) frequencies. We investigate the samples by
      transmission electron microscopy imaging, demonstrating that the particles
      aggregate and form chains and clusters. By using a broadband coaxial-line method,
      we extract the magnetic permeability in the frequency range from 1 to 12 GHz, and
      we study the shift of the ferromagnetic resonance (FMR) with respect to an
      externally applied magnetic field. We find that the zero-magnetic field
      ferromagnetic resonant peak shifts towards higher frequencies at finite magnetic
      fields, and the magnitude of complex permeability is reduced. At fields larger
      than 2.5 kOe the resonant frequency changes linearly with the applied magnetic
      field, demonstrating the transition to a state in which the nanoparticles become
      dynamically decoupled. In this regime, the particles inside clusters can be
      treated as non-interacting, and the peak position can be predicted from Kittel's
      FMR theory for non-interacting uniaxial spherical particles combined with the
      Landau-Lifshitz-Gilbert equation. In contrast, at low magnetic fields this
      magnetic order breaks down and the resonant frequency in zero magnetic field
      reaches a saturation value reflecting the interparticle interactions as resulting
      from aggregation. Our results show that the electromagnetic properties of these
      composite materials can be tuned by external magnetic fields and by changes in
      the aggregation structure. 

PMID- 25397946
TI  - From deep-sea volcanoes to human pathogens: a conserved quorum-sensing signal in
      Epsilonproteobacteria.
AB  - Chemosynthetic Epsilonproteobacteria from deep-sea hydrothermal vents colonize
      substrates exposed to steep thermal and redox gradients. In many bacteria,
      substrate attachment, biofilm formation, expression of virulence genes and host
      colonization are partly controlled via a cell density-dependent mechanism
      involving signal molecules, known as quorum sensing. Within the
      Epsilonproteobacteria, quorum sensing has been investigated only in human
      pathogens that use the luxS/autoinducer-2 (AI-2) mechanism to control the
      expression of some of these functions. In this study we showed that luxS is
      conserved in Epsilonproteobacteria and that pathogenic and mesophilic members of
      this class inherited this gene from a thermophilic ancestor. Furthermore, we
      provide evidence that the luxS gene is expressed--and a quorum-sensing signal is
      produced--during growth of Sulfurovum lithotrophicum and Caminibacter
      mediatlanticus, two Epsilonproteobacteria from deep-sea hydrothermal vents.
      Finally, we detected luxS transcripts in Epsilonproteobacteria-dominated biofilm
      communities collected from deep-sea hydrothermal vents. Taken together, our
      findings indicate that the epsiloproteobacterial lineage of the LuxS enzyme
      originated in high-temperature geothermal environments and that, in vent
      Epsilonproteobacteria, luxS expression is linked to the production of AI-2
      signals, which are likely produced in situ at deep-sea vents. We conclude that
      the luxS gene is part of the ancestral epsilonproteobacterial genome and
      represents an evolutionary link that connects thermophiles to human pathogens.

PMID- 25397947
TI  - Phenotypic plasticity in heterotrophic marine microbial communities in continuous
      cultures.
AB  - Phenotypic plasticity (PP) is the development of alternate phenotypes of a given
      taxon as an adaptation to environmental conditions. Methodological limitations
      have restricted the quantification of PP to the measurement of a few traits in
      single organisms. We used metatranscriptomic libraries to overcome these
      challenges and estimate PP using the expressed genes of multiple heterotrophic
      organisms as a proxy for traits in a microbial community. The metatranscriptomes
      captured the expression response of natural marine bacterial communities grown on
      differing carbon resource regimes in continuous cultures. We found that taxa with
      different magnitudes of PP coexisted in the same cultures, and that members of
      the order Rhodobacterales had the highest levels of PP. In agreement with
      previous studies, our results suggest that continuous culturing may have
      specifically selected for taxa featuring a rather high range of PP. On average,
      PP and abundance changes within a taxon contributed equally to the organism's
      change in functional gene abundance, implying that both PP and abundance mediated
      observed differences in community function. However, not all functional changes
      due to PP were directly reflected in the bulk community functional response: gene
      expression changes in individual taxa due to PP were partly masked by
      counterbalanced expression of the same gene in other taxa. This observation
      demonstrates that PP had a stabilizing effect on a community's functional
      response to environmental change. 

PMID- 25397949
TI  - Effect of fasudil hydrochloride on the post-thaw viability of cryopreserved
      porcine adipose-derived stem cells.
AB  - BACKGROUND: Adipose-derived stem cells (ADSCs) are of interest for regenerative
      medicine as they are isolated easily and can differentiate into multiple cell
      lineages. Recently, it was reported that a Rho-associated kinase (ROCK) inhibitor
      Y-27632 could enhance the post-thaw viability and physiological function of
      cryopreserved BMSC. OBJECTIVE: The present study is to investigate whether
      Fasudil hydrochloride (FH, a selective Rho-kinase inhibitor like Y-27632) can
      exert a similar beneficial effect on the post-thaw viability of cryopreserved
      ADSCs. METHODS: ADSCs were allotted in three cryopreservation solutions [I:10 %
      (v/v) (DMSO), 30 % (v/v) FBS (as a negative control); II:10uM FH, 10 % (v/v)
      DMSO, 30 % (v/v) FBS; III:10 uM Y-27632, 10 % (v/v) DMSO, 30 % (v/v) fetal bovine
      serum, All groups were frozen using a rapid freezing method and stored at -196
      degree C in liquid nitrogen for 30 days.After thawing and being cultured
      24h,viability of ADSCs were detected by MTT assay. RESULT: The MTT assay showed
      significant differences in the proportion of adherent viable cells over the
      concentration of Y-27632 and FH, Additionally, FH did not induce morphological
      changes in the frozen-thawed ADSCs like Y-27632 did. CONCLUSIONS: FH might
      represent a promising cryopreservation solution in enhancing the post-thaw
      viability and physiological function of cryopreserved ADSCs and did not chang the
      cell appearance.

PMID- 25397948
TI  - Heart mitochondrial proteome study elucidates changes in cardiac energy
      metabolism and antioxidant PRDX3 in human dilated cardiomyopathy.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is a public health problem with no
      available curative treatment, and mitochondrial dysfunction plays a critical role
      in its development. The present study is the first to analyze the mitochondrial
      proteome in cardiac tissue of patients with DCM to identify potential molecular
      targets for its therapeutic intervention. METHODS AND RESULTS: 16 left
      ventricular (LV) samples obtained from explanted human hearts with DCM (n = 8)
      and control donors (n = 8) were extracted to perform a proteomic approach to
      investigate the variations in mitochondrial protein expression. The proteome of
      the samples was analyzed by quantitative differential electrophoresis and Mass
      Spectrometry. These changes were validated by classical techniques and by novel
      and precise selected reaction monitoring analysis and RNA sequencing approach
      increasing the total heart samples up to 25. We found significant alterations in
      energy metabolism, especially in molecules involved in substrate utilization
      (ODPA, ETFD, DLDH), energy production (ATPA), other metabolic pathways (AL4A1)
      and protein synthesis (EFTU), obtaining considerable and specific relationships
      between the alterations detected in these processes. Importantly, we observed
      that the antioxidant PRDX3 overexpression is associated with impaired ventricular
      function. PRDX3 is significantly related to LV end systolic and diastolic
      diameter (r = 0.73, p value<0.01; r = 0.71, p value<0.01), fractional shortening,
      and ejection fraction (r = -0.61, p value<0.05; and r = -0.62, p value<0.05,
      respectively). CONCLUSION: This work could be a pivotal study to gain more
      knowledge on the cellular mechanisms related to the pathophysiology of this
      disease and may lead to the development of etiology-specific heart failure
      therapies. We suggest new molecular targets for therapeutic interventions,
      something that up to now has been lacking.

PMID- 25397950
TI  - Efficacy of fish embryo vitrification protocols in terms of embryo morphology - a
      systematic review.
AB  - BACKGROUND: Embryo cryopreservation has been used for the creation of genetic
      banks with diploid resources, and among different techniques, vitrification is
      considered as the most promising method. OBJECTIVE: The goal is to evaluate the
      major aspects of the existing vitrification techniques and to evaluate their
      efficacy in terms of embryo morphology. METHODS: Electronic searches in the
      PubMed and ScienceDirect databases were performed with the keyword combination:
      fish, embryo and vitrification. Pubmed retrieved 26 articles and Science Direct
      resulted in 464 articles. For this review, only studies that developed and tested
      vitrification protocols in fish embryos were included. Research regarding
      cryoprotectant toxicity and permeability were excluded. There were no
      restrictions on publication date or language. With these criteria, a total of ten
      articles were evaluated. RESULTS: In these articles, the major aspects to be
      considered for the development of new vitrification protocols are: the
      cryoprotectants' toxicity, the embryos' development stage, the exposure to and
      the permeability of the cryoprotectants, vitrification devices and vitrification
      warning cycle. CONCLUSION: The survival were limited, however, the preservation
      of embryonic morphology after thawing indicates the possibility of preserving
      fish embryos via the vitrification technique.

PMID- 25397951
TI  - Effect of ultrasonic waves on the freezing rates of potatoes in degassed coolant
      and untreated coolant.
AB  - BACKGROUND: Ultrasonic waves are shown to enhance the rate of freezing.
      OBJECTIVE: To elucidate the mechanism of immersion freezing of potatos with
      ultrasonic waves. MATERIALS AND METHODS: Ultrasound is applied to potato samples
      immersed in degassed coolant and untreated coolant. Sonic waves were
      intermittently applied at temperature below -1 degree C. The freezing rates were
      measured under different experimental conditions. RESULTS: The use of ultrasonic
      waves increased the freezing rates of potatoes immersed in both degassed coolant
      and untreated coolant. However, the freezing rate in the degassed coolant was
      less than that in the untreated coolant. CONCLUSION: Heat transfer on the
      interface between the potato sample and sonicated degassed coolant appears to be
      less than that within the sample in the absence of cavitation. The interface heat
      transfer between the potato sample and untreated coolant is likely improved due
      to ultrasonic cavitation.

PMID- 25397952
TI  - Development of an encapsulation-vitrification protocol for Rubia akane (nakai)
      hairy roots: a comparison with non-encapsulation.
AB  - BACKGROUND: A comparison of different cryopreservation techniques should be based
      on the characteristics of both the methodology and the material in question using
      an optimized procedure. OBJECTIVE: This study aimed at developing an
      encapsulation-vitrification procedure for hairy roots of Rubia akane using
      alternative loading and vitrification solutions, based on the existing optimized
      droplet-vitrification procedure. MATERIALS AND METHODS: Encapsulated roots were
      first precultured in liquid medium with 10% sucrose for 3 days, then with 17.5 %
      sucrose for 1 day, after which they were osmoprotected with solution C6-40 % (20
      % glycerol + 20 % sucrose) for 50 min, cryoprotected with solution A3-90 % (37.5
      % glycerol + 15 % DMSO + 15 % EG + 22.5 % sucrose, w/v) on ice for 40 min, cooled
      and warmed in 2 ml cryovials, and unloaded in 35% sucrose solution for 60 min.
      RESULTS: Through the application of this procedure to aged-clustered roots, up to
      97.5 % post-cryopreservation regeneration was observed. In our previous study,
      droplet-vitrification of hairy roots of R. akane resulted in 83.8 % post
      rewarming regeneration following preculture with 10 % sucrose for 2 days and 17.5
      % sucrose for 4-5 h, and osmoprotection with solution C4-35 % (17.5 % glycerol +
      17.5 % sucrose) for 30 min, and cryoprotection with solution A3-70 % (29.2 %
      glycerol + 11.7 % DMSO + 11.7% EG + 17.4% sucrose, w/v) on ice for 20 min. In the
      present study, higher post-cryopreservation regeneration was observed by using a
      higher concentration of vitrification solution (A3-70 % -> A3-90 %, B5-80 % -> B1
      100 %) and/or a longer cryoprotection duration (A3-70 % at room temperature (RT)
      for 8 min -> 15-30 min, on ice for 20 min -> 40-80 min; B5-80 % for 15 min -> 30
      60 min). CONCLUSION: Even though encapsulation provided some degree of protection
      from the cytotoxicity of vitrification solutions to cytotoxicity-sensitive R.
      akane hairy roots, an overall higher post-cryopreservation regrowth was obtained
      using the droplet-vitrification procedure under optimized conditions. This result
      implies that this sensitive material was not sufficiently cryoprotected, and
      thus, rapid cooling and warming using foil strips was more efficient than
      cryopreservation of encapsulated samples.

PMID- 25397953
TI  - Cryopreservation of dormant in vivo-buds of hybrid aspen: timing as a critical
      factor.
AB  - BACKGROUND: For the conservation of hybrid aspen germplasm, cryostorage of
      dormant in vivo buds is a convenient back-up method for field collections. In
      practice in Finland, bud collection is performed from February to March.
      OBJECTIVE: The aim of this study was to assess how this time schedule can be
      extended without compromising regeneration. In addition, an easily measurable
      marker for successful cryopreservation was examined. MATERIALS AND METHODS:
      Timing of cryopreservation was tested from August to February, using dormant buds
      from both outdoor and indoor plants. To find a marker, water content and gene
      expression of hydrid aspens, as well as environmental factors such as
      temperature, temperature sum, and light period were followed. RESULTS:
      Cryopreservation was successful from October to February, when, on an average, at
      least 75 % of the buds regenerated through micropropagation, and there was no
      difference to non-frozen controls. Significant genotypic variation was observed
      in October and February, with regeneration rates of 61-100 % and 37-98 %,
      respectively. No marker for successful cryopreservation was found among the
      studied factors. CONCLUSION: The results provide flexibility for the undertaking
      of practical work, with a recommendation that cryopreservation can be carried out
      from November to January - earlier than the current practice.

PMID- 25397954
TI  - Extracellular ice phase transitions in insects.
AB  - At temperatures below their temperature of crystallization (Tc), the
      extracellular body fluids of insects undergo a phase transition from liquid to
      solid. Insects that survive the transition to equilibrium (complete freezing of
      the body fluids) are designated as freeze tolerant. Although this phenomenon has
      been reported and described in many Insecta, current nomenclature and theory does
      not clearly delineate between the process of transition (freezing) and the final
      solid phase itself (the frozen state). Thus freeze tolerant insects are
      currently, by convention, described in terms of the temperature at which the
      crystallization of their body fluids is initiated, Tc. In fact, the correct
      descriptor for insects that tolerate freezing is the temperature of equilibrium
      freezing, Tef. The process of freezing is itself a separate physical event with
      unique physiological stresses that are associated with ice growth.
      Correspondingly there are a number of insects whose physiological cryo-limits are
      very specifically delineated by this transitional envelope. The distinction also
      has considerable significance for our understanding of insect cryobiology:
      firstly, because the ability to manage endogenous ice growth is a fundamental
      segregator of cryotype; and secondly, because our understanding of internal ice
      management is still largely nascent. 

PMID- 25397955
TI  - Production of organ extracellular matrix using a freeze-thaw cycle employing
      extracellular cryoprotectants.
AB  - Biologic scaffold materials composed of the extracellular matrix (ECM) are
      typically derived by processes that involve decellularization of tissues or
      organs. All decellularization methods result in the ECM architecture disruption
      and a potential loss of surface structure and composition. Freeze-thaw processing
      effectively lyses cells and permits to diminish amounts of chemical lysing agents
      henceforth. However, it also causes certain disruptions of the ECM
      ultrastructure. In order to diminish these adverse effects we suggested using
      extracellular cryoprotectants (namely 5 % trehalose) to preserve the ECM
      molecular network without impeding the cell lysis. The original optimization of
      the perfusion-mediated decellularization method to comprise the single freeze
      thaw processing cycle and subsequent perfusion with chemical agents' solution is
      presented here. 

PMID- 25397956
TI  - Coconut (Cocos nucifera l.) pollen cryopreservation.
AB  - BACKGROUND: Coconut genetic resources are threatened by pests and pathogens,
      natural hazards and human activities. Cryopreservation is the only method
      allowing the safe and cost-effective long-term conservation of recalcitrant seed
      species such as coconut. OBJECTIVE: The objective of this work was to test the
      effect of cryopreservation and of cryostorage duration on coconut pollen
      germination and fertility. MATERIALS AND METHODS: Pollen of two coconut varieties
      (West Coast Tall WWCTW and Chowghat Orange Dwarf CODC) was collected in March-May
      over three successive years, desiccated to 7.5 % moisture content (FW) and
      cryopreserved by direct immersion in liquid nitrogen. RESULTS: Germination and
      pollen tube length (PTL) of desiccated and cryopreserved pollen were not
      significantly different for both WCT and COD over the three harvest months of the
      three consecutive years of study. Pollen germination ranged from 24 to 32 % in
      desiccated pollen whereas it was between 26 and 29 % in cryopreserved COD pollen.
      In the case of WCT, germination ranged from 30 to 31 % in desiccated pollen,
      while it was between 28 and 32 % in cryopreserved pollen. PTL of cryopreserved
      pollen ranged between 224-390 nm and 226-396 mm for COD and WCT, respectively.
      Germination of COD pollen varied between 29.0 and 44.1 % after 4 years and
      1.0/1.5 years cryostorage, respectively. Germination of WCT pollen did not change
      significantly between 0 and 6 years cryostorage, being comprised between 32 (24
      h) and 40 % (1.5 years). Germination and vigour of cryopreserved pollen were
      generally higher compared to that of pollen dried in oven and non-cryopreserved.
      Normal seed set was observed in COD and WCT palms using pollen cryostored for 6
      months and 4 years. Cryopreserved pollen of five Tall and five Dwarf accessions
      displayed 24-31 % and 25-49 % germination, respectively. CONCLUSION: These
      results show that it is now possible to establish pollen cryobanks to contribute
      to coconut germplasm long-term conservation.

PMID- 25397957
TI  - Low-temperature storage and cryopreservation of grapefruit (Citrus paradisi
      Macfad.) seeds.
AB  - BACKGROUND: Grapefruit is an economically important fruit worldwide, but our
      knowledge of its seed biology is rather poor. OBJECTIVE: The present study aimed
      to develop techniques for banking and cryopreservation of grapefruit seeds.
      MATERIALS AND METHODS: Grapefruit seeds with the exotesta removed were used.
      Seeds were desiccated to three moisture levels between 5-9 % and stored at 15
      degree C, 4 degree C and -20 degree C for up to 24, months to investigate seed
      lifespan in conventional seed bank. Meanwhile seeds desiccated by silica gel or
      saturated salt solution and embryonic axes by flash drying were employed to
      develop cryopreservation protocols. RESULTS: It was confirmed that grapefruit
      seeds have some intermediate properties, being able to withstand removal of type
      II water up to 7 % MC, but sensitive to -20 degree C storage. For
      cryopreservation, the excised embryonic axes had a wider moisture window between
      5 % and 15%, with a maximum past-thaw emergence of 95 %, while seeds survived
      only with a maximum past-thaw emergence of 50 % or 70 % from a much narrow
      moisture window. CONCLUSION: In contrast to previous reports on another type II
      seed, coffee, we found that citrus seeds desiccated by silica gel had better post
      thaw viability than those subjected to equilibrium desiccation with saturated
      salt solutions. Further investigation is required to elucidate the mechanisms
      that contribute to variable cryopreservation tolerance.

PMID- 25397958
TI  - Evaluation of cryoprotective effect of Turkish pine honey on common carp
      (Cyprinus carpio) spermatozoa.
AB  - BACKGROUND: The cryopreservation procedures that allow preserving sperm cells
      have been applied for sperm of many species. A sugar like glucose, fructose and
      sucrose were frequently used in cryomedia but up to the present pine honey was
      not used for cryopreservation of sperm cells. OBJECTIVE: The objective of present
      study is to investigate the effect of pine honey in various concentrations of
      100, 200, 300, 400 and 500 mg/ml solutions on cryopreservation and fertilization
      ability of spermatozoa of common carp (Cyprinus carpio). MATERIALS AND METHODS:
      Totally 12.5 % (v/v) Me2SO as a cryoprotectant and 10 % (v/v) egg yolk added all
      extenders. Pine honey also compared with sugars as glucose, fructose
      (monosaccharide) and sucrose (disaccharide). Collected semen samples were diluted
      at the ratio of 1:9 with the extenders. After dilutions, the sperm motility was
      assessed for each group and then the diluted semen samples were cryopreserved.
      RESULTS: The extenders containing 300 mg ml-1 pine honey group showed both
      highest post thaw motility 75.3 +/- 5.1 %, motility duration (s) 47.3 +/- 2.5 %
      and hatching ratio 42.6 +/- 4.2 % than other cryopreserved groups (P<0.05).
      CONCLUSION: Using the pine honey in cryomedia is effective for cryopreservation
      especially about hatching success of egg fertilized by frozen-thawed sperm of
      common carp.

PMID- 25397959
TI  - Characterization and expression analysis of six chitinase genes from the desert
      beetle Microdera punctipennis in response to low temperature.
AB  - BACKGROUND: Chitinase is responsible for chitin metabolism in a wide range of
      organisms. However, current knowledge on insect chitinase and their possible
      functions in relation to low temperature stress is very limited. OBJECTIVE: Six
      chitinase genes from cold treated desert beetle Microdera punctipennis obtained
      by RNA-seq technology were characterized, and their expression patterns in
      different tissues and in response to cold were investigated. METHODS: Multiple
      sequence alignment was carried out using ClustalW1.81 and Phylogenetic trees were
      generated by MEGA5. The expression patterns were studied by quantitative real
      time PCR. RESULTS: These genes were belong to three different chitinase groups.
      Almost all of them were highly expressed in midgut, and some are expressed in fat
      body or hindgut. Subzero-4 degree C had stronger effect than 4 degree C in
      inducing chitinase expression. CONCLUSION: The tissue specific and cold inducible
      expressions suggest that the chitinases may have diverse functions and play roles
      in insect cold adaptation.

PMID- 25397961
TI  - A new multienzyme-type biosensor for triglyceride determination.
AB  - An amperometric multienzyme biosensor for determination of triglycerides (TGs)
      was constructed by mounting three gelatin membrane-bound enzymes on a glassy
      carbon electrode (working electrode), then connecting it to electrometer along
      with an Ag/AgCl reference electrode and a Pt auxiliary electrode.
      Characterization and optimization of the multienzyme biosensor, which is prepared
      with glycerol kinase (GK) (E.C.2.7.1.30), glycerol-3-phosphate oxidase (GPO) (EC
      1.1.3.21), and lipase (EC 3.1.1.3), were studied. In the optimization studies for
      the bioactive layer components of the prepared biosensor, the optimum amounts of
      gelatin, bovine serum albumin (BSA), and glutaraldehyde was calculated as 1
      mg/cm(2), 1 mg/cm(2), and 2.5%, respectively. Optimum pH and temperature of the
      reaction of biosensor were determined as 7.0 and 40  degrees C, respectively.
      Linear range of triolein for the biosensor was found from the calibration curve
      between several substrate concentration and Delta Current. After optimization and
      characterization of the biosensor, its operationability in triglycerides was also
      tested.

PMID- 25397960
TI  - Proximal tubule dysfunction is associated with podocyte damage biomarkers nephrin
      and vascular endothelial growth factor in type 2 diabetes mellitus patients: a
      cross-sectional study.
AB  - BACKGROUND: There is an ongoing debate as to whether early diabetic nephropathy
      in Type 2 diabetes mellitus may be attributed to the glomerulus or to the
      proximal tubule. Urinary excretion of nephrin and vascular endothelial growth
      factor may increase even in the normoalbuminuria stage. In the course of diabetic
      nephropathy, the proximal tubule may be involved in the uptake of urinary nephrin
      and vascular endothelial growth factor. MATERIALS AND METHODS: Two groups of
      consecutive Type 2 diabetes mellitus outpatients (38 normo-, 32 microalbuminuric)
      and 21 healthy subjects were enrolled in a cross-sectional study and evaluated
      concerning the relation of proximal tubule dysfunction with the podocyte
      biomarkers excretion, assessed by ELISA methods. The impact of advanced glycation
      end-products on this relation was also queried. RESULTS: Urinary alpha1
      microglobulin and kidney injury molecule-1 correlated with urinary
      albumin:creatinine ratio (R2 = 0.269; p < 0.001; R2 = 0.125; p < 0.001),
      nephrinuria (R2 = 0.529; p<0.001; R2 = 0.203; p < 0.001), urinary vascular
      endothelial growth factor (R2 = 0.709; p < 0.001; R2 = 0.360; p < 0.001), urinary
      advanced glycation end-products (R2 = 0.578; p < 0.001; R2 = 0.405; p < 0.001),
      serum cystatin C (R2 = 0.130; p < 0.001; R2 = 0.128; p<0.001), and glomerular
      filtration rate (R2 = 0.167; p < 0.001; R2 = 0.166; p < 0.001); nephrinuria and
      urinary vascular endothelial growth factor correlated with urinary
      albumin:creatinine ratio (R2 = 0.498; p < 0.001; R2 = 0.227; p<0.001), urinary
      advanced glycation end-products (R2 = 0.251; p < 0.001; R2 = 0.308; p < 0.001),
      serum cystatin C (R2 = 0.157; p < 0.001; R2 = 0.226; p < 0.001), and glomerular
      filtration rate (R2 = 0.087; p = 0.007; R2 = 0.218; p < 0.001). CONCLUSIONS: In
      Type 2 diabetes mellitus there is an association of proximal tubule dysfunction
      with podocyte damage biomarkers, even in the normoalbuminuria stage. This
      observation suggests a potential role of the proximal tubule in urinary nephrin
      and urinary vascular endothelial growth factor processing in early diabetic
      nephropathy, a fact which could be related to advanced glycation end-products
      intervention. Podocyte damage and proximal tubule dysfunction biomarkers could be
      validated as a practical approach to the diagnosis of early diabetic nephropathy
      by further studies on larger cohorts.

PMID- 25397962
TI  - Re-evaluation of the AASHTO-flexible pavement design equation with neural network
      modeling.
AB  - Here we establish that equivalent single-axle loads values can be estimated using
      artificial neural networks without the complex design equality of American
      Association of State Highway and Transportation Officials (AASHTO). More
      importantly, we find that the neural network model gives the coefficients to be
      able to obtain the actual load values using the AASHTO design values. Thus, those
      design traffic values that might result in deterioration can be better calculated
      using the neural networks model than with the AASHTO design equation. The
      artificial neural network method is used for this purpose. The existing AASHTO
      flexible pavement design equation does not currently predict the pavement
      performance of the strategic highway research program (Long Term Pavement
      Performance studies) test sections very accurately, and typically over-estimates
      the number of equivalent single axle loads needed to cause a measured loss of the
      present serviceability index. Here we aimed to demonstrate that the proposed
      neural network model can more accurately represent the loads values data,
      compared against the performance of the AASHTO formula. It is concluded that the
      neural network may be an appropriate tool for the development of databased
      nonparametric models of pavement performance. 

PMID- 25397963
TI  - Mindful caring: using mindfulness-based cognitive therapy with caregivers of
      cancer survivors.
AB  - Caregivers of cancer survivors face many burdens that often require treatment by
      mental health professionals. One intervention, mindfulness-based cognitive
      therapy, aims to help individuals change the ways in which they relate to their
      thoughts rather than changing their thoughts. In this manuscript, we discuss the
      use and adaption of mindfulness-based cognitive therapy with caregivers of cancer
      survivors as a way to decrease caregiver burden and increase caregiver quality of
      life. A session-by-session breakdown of how to tailor mindfulness-based cognitive
      therapy to caregivers of cancer survivors is provided. 

PMID- 25397964
TI  - Are Elderly Patients With Clinically Localized Prostate Cancer Overtreated?
      Exploring Heterogeneity in Survival Effects.
AB  - BACKGROUND: Clinical trial evidence shows minimal survival gains and higher
      complication rates from radical prostatectomy (RP) versus watchful waiting (WW)
      for elderly men with localized prostate cancer (PCa). It is believed that these
      patients are overtreated. The current analyses aim to explore patient-level
      heterogeneity in survival effects, examine matching of patients to treatments in
      practice, and identify patient characteristics driving heterogenous effects, in
      order to present more comprehensive evidence about the concerns of overtreatment.
      METHODS: Eleven-year all-cause and PCa-specific survival among SEER-Medicare
      patients diagnosed during 1996-2002 were analyzed using local instrumental
      variable approaches. RESULTS: A total of 8462 (77%) of 11,036 patients received
      RP. The average effects of RP over WW on 11-year overall and cancer-specific
      survival were 1.1 months (95%CI, -25, 28; P=0.94) and 1.7 months (95%CI, -25, 29;
      P=0.90) respectively; effects did not differ significantly according to age,
      race, grade, and stage. Fewer than 1% of patients had significant cancer-specific
      survival benefit from RP at the 10% level; 6% were expected to gain over 15
      months from RP. However, patients with larger expected survival gains from RP
      were much more likely to receive RP in practice. Such positive self-selection was
      driven by PCa-specific survival than overall survival. Several comorbidities may
      play a critical role in predicting who could benefit from RP. CONCLUSIONS: Our
      analyses corroborate concerns about PCa overtreatment. A small fraction of screen
      detected PCa patients derive survival benefits from RP. Prediction tools should
      account for patient comorbidities to accurately predict survival benefits of RP
      over WW.

PMID- 25397965
TI  - Variation in US hospital emergency department admission rates by clinical
      condition.
AB  - BACKGROUND: Variation in hospitalization rates have been described for decades,
      yet little is known about variation in emergency department (ED) admission rates
      across clinical conditions. We sought to describe variation in ED risk
      standardized admission rates (RSAR) and the consistency between condition
      specific ED admission rates within hospitals. METHODS: Cross-sectional analysis
      of the 2009 National Emergency Department Sample, an all-payer administrative,
      claims dataset. We identify the 15 most frequently admitted conditions using
      Clinical Classification Software. To identify conditions with the highest ED RSAR
      variation, we compared both the ratio of the 75th percentile to the 25th
      percentile hospital and coefficient of variation between conditions. We calculate
      Spearman correlation coefficients to assess within-hospital correlation of
      condition-specific ED RSARs. RESULTS: Of 21,885,845 adult ED visits, 4,470,105
      (20%) resulted in admission. Among the 15 most frequently admitted conditions,
      the 5 with the highest magnitude of variation were: mood disorders (ratio of
      75th:25th percentile, 6.97; coefficient of variation, 0.81), nonspecific chest
      pain (2.68; 0.66), skin and soft tissue infections (1.82; 0.51), urinary tract
      infections (1.58; 0.43), and chronic obstructive pulmonary disease (1.57; 0.33).
      For these 5 conditions, the within-hospital RSAR correlations between each pair
      of conditions were >0.4, except for mood disorders, which was poorly correlated
      with all other conditions (r<0.3). CONCLUSIONS: There is significant condition
      specific variation in ED admission rates across US hospitals. This variation
      appears to be consistent between conditions with high variation within hospitals.

PMID- 25397966
TI  - Cost-effectiveness of diabetes pay-for-performance incentive designs.
AB  - BACKGROUND: Taiwan's National Health Insurance (NHI) Program implemented a
      diabetes pay-for-performance program (P4P) based on process-of-care measures in
      2001. In late 2006, that P4P program was revised to also include achievement of
      intermediate health outcomes. OBJECTIVES: This study examined to what extent
      these 2 P4P incentive designs have been cost-effective and what the difference in
      effect may have been. RESEARCH DESIGN AND METHOD: Analyzing data using 3
      population-based longitudinal databases (NHI's P4P dataset, NHI's claims
      database, and Taiwan's death registry), we compared costs and effectiveness
      between P4P and non-P4P diabetes patient groups in each phase. Propensity score
      matching was used to match comparable control groups for intervention groups.
      Outcomes included life-years, quality-adjusted life-years (QALYs), program
      intervention costs, cost-savings, and incremental cost-effectiveness ratios.
      RESULTS: QALYs for P4P patients and non-P4P patients were 2.08 and 1.99 in phase
      1 and 2.08 and 2.02 in phase 2. The average incremental intervention costs per
      QALYs was TWD$335,546 in phase 1 and TWD$298,606 in phase 2. The average
      incremental all-cause medical costs saved by the P4P program per QALYs were
      TWD$602,167 in phase 1 and TWD$661,163 in phase 2. The findings indicated that
      both P4P programs were cost-effective and the resulting return on investment was
      1.8:1 in phase 1 and 2.0:1 in phase 2. CONCLUSIONS: We conclude that the diabetes
      P4P program in both phases enabled the long-term cost-effective use of resources
      and cost-savings regardless of whether a bonus for intermediate outcome
      improvement was added to a process-based P4P incentive design.

PMID- 25397967
TI  - Genetic analysis of loop sequences in the let-7 gene family reveal a relationship
      between loop evolution and multiple isomiRs.
AB  - While mature miRNAs have been widely studied, the terminal loop sequences are
      rarely examined despite regulating both primary and mature miRNA functions.
      Herein, we attempted to understand the evolutionary pattern of loop sequences by
      analyzing loops in the let-7 gene family. Compared to the stable miRNA length
      distributions seen in most metazoans, higher metazoan species exhibit a longer
      length distribution. Examination of these loop sequence length distributions, in
      addition to phylogenetic tree construction, implicated loop sequences as the main
      evolutionary drivers in miRNA genes. Moreover, loops from relevant clustered
      miRNA gene families showed varying length distributions and higher levels of
      nucleotide divergence, even between homologous pre-miRNA loops. Furthermore, we
      found that specific nucleotides were dominantly distributed in the 5' and 3'
      terminal loop ends, which may contribute to the relatively precise cleavage that
      leads to a stable isomiR expression profile. Overall, this study provides further
      insight into miRNA processing and maturation and further enriches our
      understanding of miRNA biogenesis. 

PMID- 25397970
TI  - Nursing students' attitudes about psychiatric mental health nursing.
AB  - The purpose of this study was to describe Masters entry nursing students'
      attitudes about psychiatric mental health clinical experiences; preparedness to
      care for persons with mental illness; students' perceived stigmas and
      stereotypes; and plans to choose mental health nursing as a career. A 31-item
      survey was administered to pre-licensure graduate nursing students who were
      recruited from a Masters entry nursing program from a university in a large city
      in the Midwestern US. Results indicated that clinical experiences provide
      valuable experiences for nursing practice, however, fewer students think that
      these experiences prepare them to work as a psychiatric mental health nurse and
      none plan to pursue careers as psychiatric mental health nurses. The findings
      support conclusions from other studies that increasing the amount of time in the
      clinical setting and adding specific content to the curriculum, particularly
      content related to the importance of psychiatric mental health nursing and the
      effects of stigma, may assist the profession's efforts to recruit and retain
      psychiatric mental health nurses. Further research is needed to determine the
      effectiveness of these strategies and to identify the best ways to implement
      them. 

PMID- 25397968
TI  - Final height and cardiometabolic outcomes in young adults with very low birth
      weight (<1500 g).
AB  - OBJECTIVE: Individuals with very low birth weight (VLBW; <1500 g) are known to be
      predisposed to both short final height and cardiometabolic disorders. However,
      associations between final height and cardiometabolic outcomes including glucose
      metabolism in VLBW individuals in young adulthood are not fully investigated.
      METHODS: We investigated glucose metabolism and other cardiometabolic outcomes
      such as lipid profiles, blood pressure, renal function, urinary albumin, and
      thyroid function in young adults with VLBW born between 1980 and 1990. Short
      stature was defined as a final height <10th percentile. Glucose intolerance
      [diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG)]
      was determined using 75-g oral glucose tolerance tests. Associations between
      final height and cardiometabolic outcomes were examined using logistic or
      multiple linear regression. RESULTS: A total of 628 VLBW individuals were
      screened and 111 young adults with VLBW (19-30 years) participated in the study.
      Of the participants, 40 subjects (36%) had short stature with a final height
      <10th percentile. Eight subjects (7.2%) had glucose intolerance (1, diabetes; 6,
      IGT; 1, IFG). Short stature was correlated with glucose intolerance (odds ratio
      11.1; 95% CI 1.92, 99.7; P = 0.006). Final height was inversely associated with
      the homeostatic model assessment (HOMA) of insulin resistance, HOMA-beta,
      insulinogenic index, and total/LDL-cholesterol. The associations of final height
      with insulin sensitivity and lipid profiles remained after adjustment for target
      height and age at puberty onset. CONCLUSIONS: Shorter final height was associated
      with less favorable metabolic profiles in young adults with VLBW, and may be
      partly mediated by reduced insulin sensitivity. These associations were
      independent of target height or age at puberty onset.

PMID- 25397971
TI  - A novel simple assay system to quantify the percent HCV-RNA levels of NS5A Y93H
      mutant strains and Y93 wild-type strains relative to the total HCV-RNA levels to
      determine the indication for antiviral therapy with NS5A inhibitors.
AB  - AIM: Oral treatment with asunaprevir and daclatasvir has been reported to yield a
      SVR ratio of 80% in patients with genotype 1b HCV infection, however, treatment
      failure has been reported, especially in patients with HCV strains showing the
      NS5A-Y93H mutation at baseline. An assay system to detect such strains was
      established to facilitate selection of appropriate candidates for this antiviral
      therapy. METHODS: Primer sets and 2 types of cycling probe mixtures were
      designed, and real-time PCR was performed with HCV-RNA purified from 332 patients
      with genotype 1b HCV infection, and the results were compared with those obtained
      by direct sequencing. RESULTS: Both the wild-type and mutant strains were
      quantified, with a threshold of 4.0 Log copies/mL, in 295 of the 332 patients
      (88.9%), and the percentage of the mutant strains relative to the total HCV-RNA
      level in the serum was calculated. The percentage was 0% in 237 patients (80.3%)
      and 100% in 23 patients (7.8%), identical to the results of direct sequencing.
      Both wild-type and mutant strains were detected in the remaining 35 patients
      (11.9%), at levels between 1% and 99%, despite the mutant strains having been
      undetectable by direct sequencing in 11 patients with percentages of these
      strains of less than 25%. CONCLUSION: A novel assay system to quantify the
      percent RNA of Y93H mutant strains relative to the total HCV-RNA level was
      established. This system may be useful to determine the indication for treatment
      with NA5A inhibitors in patients with HCV.

PMID- 25397973
TI  - The effect of presentation rate on foreign-language vocabulary learning.
AB  - The present study examined the effect of presentation rate on foreign-language
      vocabulary learning. Experiment 1 varied presentation rates from 1 s to 16 s per
      pair while keeping the total study time per pair constant. Speakers of English
      studied Dutch-English translation pairs (e.g., kikker-frog) for 16 * 1 s, 8 * 2
      s, 4 * 4 s, 2 * 8 s, or 1 * 16 s. The results showed a nonmonotonic relationship
      between presentation rate and recall performance for both translation directions
      (Dutch -> English and English -> Dutch). Performance was best for intermediate
      presentation rates and dropped off for short (1 s) or long (16 s) presentation
      rates. Experiment 2 showed that the nonmonotonic relationship between
      presentation rate and recall performance was still present after a 1-day
      retention interval for both translation directions. Our results suggest that a
      presentation rate in the order of 4 s results in optimal learning of foreign
      language vocabulary.

PMID- 25397974
TI  - Belongingness and suicidal ideation in college students.
AB  - OBJECTIVE: In this study, the relationships between 3 specific domains of
      belongingness (ie, family, peers, and academic institution) were examined with
      respect to suicidal ideation. PARTICIPANTS: A sample (N=249) of undergraduate
      students was recruited from a large, midwestern university during the Spring 2013
      semester. METHODS: Multiple regression analysis examined whether the 3 specific
      domains of belongingness (ie, family, peers, and academic institution)
      significantly contributed to explaining variance in suicidal ideation. RESULTS:
      Findings indicated that the 3 domains of belongingness accounted for 9.4% of the
      variance for suicidal ideation. Family belongingness was the only domain of
      belongingness that made a significant, unique, and negative contribution to
      suicidal ideation. CONCLUSIONS: Students' family belongingness seems to have a
      significant role in their manifestation of suicidal ideation.

PMID- 25397972
TI  - Risk factors for asthma-related healthcare use: longitudinal analysis using the
      NHI claims database in a Korean asthma cohort.
AB  - BACKGROUND: Though insurance claims data are useful for researching asthma, they
      have important limitations, such as a diagnostic inaccuracy and a lack of
      clinical information. To overcome these drawbacks, we used the novel method by
      merging the clinical data from our asthma cohort with the National Health
      Insurance (NHI) claims data. METHODS AND RESULTS: Longitudinal analysis of asthma
      related healthcare use from the NHI claims database, merged with data of 736
      patients registered in a Korean asthma cohort, was conducted for three
      consecutive years from registration of the cohort. Asthma-related asthma
      healthcare referred to outpatient and emergency department visits,
      hospitalizations, and the use of systemic corticosteroids. Univariate and
      multivariate logistic regression analysis was used to evaluate risk factors for
      asthma-related healthcare. Over three years after enrollment, many patients
      changed from tertiary to primary/secondary hospitals with a lack of maintenance
      of inhaled corticosteroid-based controllers. An independent risk factor for
      emergency visits was a previous history of asthma exacerbation. In
      hospitalizations, old age and Asthma Control Test (ACT) score variability were
      independent risk factors. An independent risk factor for per person cumulative
      duration of systemic corticosteroids was the FEV1 (Forced expiratory volume in
      one second)%. The use of systemic corticosteroids was independently associated
      with being female, the FEV1%, and ACT score variability. CONCLUSION: We found
      that old age, being female, long-standing asthma, a low FEV1%, asthma
      brittleness, asthma drug compliance, and a history of asthma exacerbation were
      independent risk factors for increased asthma-related healthcare use in Korea.

PMID- 25397975
TI  - Feedback can be superior to observational training for both rule-based and
      information-integration category structures.
AB  - The effects of two different types of training on rule-based and information
      integration category learning were investigated in two experiments. In
      observational training, a category label is presented, followed by an example of
      that category and the participant's response. In feedback training, the stimulus
      is presented, and the participant assigns it to a category and then receives
      feedback about the accuracy of that decision. Ashby, Maddox, and Bohil (2002.
      Observational versus feedback training in rule-based and information-integration
      category learning. Memory & Cognition, 30, 666-677) reported that feedback
      training was superior to observational training when learning information
      integration category structures, but that training type had little effect on the
      acquisition of rule-based category structures. These results were argued to
      support the COVIS (competition between verbal and implicit systems) dual-process
      account of category learning. However, a number of nonessential differences
      between their rule-based and information-integration conditions complicate
      interpretation of these findings. Experiment 1 controlled between-category
      structures for participant error rates, category separation, and the number of
      stimulus dimensions relevant to the categorization. Under these more controlled
      conditions, rule-based and information-integration category structures both
      benefited from feedback training to a similar degree. Experiment 2 maintained
      this difference in training type when learning a rule-based category that had
      otherwise been matched, in terms of category overlap and overall performance,
      with the rule-based categories used in Ashby et al. These results indicate that
      differences in dimensionality between the category structures in Ashby et al. is
      a more likely explanation for the interaction between training type and category
      structure than the dual-system explanation that they offered.

PMID- 25397976
TI  - Using contaminated plants involved in phytoremediation for anaerobic digestion.
AB  - This study investigated the anaerobic digestion capability of five plants and the
      effects of copper (Cu) and S,S'-ethylenediaminedisuccinic acid (EDDS, a chelator
      widely used in chelant-assisted phytoremediation) on biogas production to
      determine a feasible disposal method for plants used in remediation. The results
      showed that in addition to Phytolacca americana L., plants such as Zea mays L.,
      Brassica napus L., Elsholtzia splendens Nakai ex F. Maekawa, and Oenothera
      biennis L. performed well in biogas production. Among these, O. biennis required
      the shortest period to finish anaerobic digestion. Compared to normal plants with
      low Cu content, the plants used in remediation with increased Cu levels (100 mg
      kg(-1)) not only promoted anaerobic digestion and required a shorter anaerobic
      digestion time, but also increased the methane content in biogas. When the Cu
      content in plants increased to 500, 1000, and 5000 mg kg(-1), the cumulative
      biogas production decreased by 12.3%, 14.6%, and 41.2%, respectively. Studies
      also found that EDDS conspicuously restrained biogas production from anaerobic
      digestion. The results suggest that anaerobic digestion has great potential for
      the disposal of contaminated plants and may provide a solution for the resource
      utilization of plants used in remediation. 

PMID- 25397977
TI  - Role of extrinsic arbuscular mycorrhizal fungi in heavy metal-contaminated
      wetlands with various soil moisture levels.
AB  - This study presents an efficient heavy metal (HM) control method in HM
      contaminated wetlands with varied soil moisture levels through the introduction
      of extrinsic arbuscular mycorrhizal fungi (AMF) into natural wetland soil
      containing indigenous AMF species. A pot culture experiment was designed to
      determine the effect of two soil water contents (5-8% and 25-30%), five extrinsic
      AMF inoculants (Glomus mosseae, G. clarum, G. claroideum, G. etunicatum, and G.
      intraradices), and HM contamination on root colonization, plant growth, and
      element uptake of common reed (Phragmites australis (Cav.) Trin. ex Steudel)
      plantlets in wetland soils. This study showed the prevalence of mycorrhizae in
      the roots of all P. australis plantlets, regardless of extrinsic AMF
      inoculations, varied soil moisture or HM levels. It seems that different
      extrinsic AMF inoculations effectively lowered HM concentrations in the
      aboveground tissues of P. australis at two soil moisture levels. However, metal
      species, metal concentrations, and soil moisture should also be very important
      factors influencing the elemental uptake performance of plants in wetland
      ecosystems. Besides, the soil moisture level significantly influenced plant
      growth (including height, and shoot and root dry weight (DW)), and extrinsic AMF
      inoculations differently affected shoot DW. 

PMID- 25397978
TI  - Species and biogeochemical cycles of organic phosphorus in sediments from a river
      with different aquatic plants located in Huaihe River Watershed, China.
AB  - The results of phosphorus fractionation in the sediments from a contaminated
      river containing different aquatic plants, analyzed by solution 31P-NMR for
      Organic Phosphorus, showed that the concentration of Inorganic Phosphorus
      dominated in all species and Organic Phosphorus accounted for over 20% of Total
      Phosphorus. In general, orthophosphate was dominant in all the sampling sites.
      The proportion of Organic Phosphorus accounting for the Total Phosphorus in the
      sediments with different plant decreased in the following order: Paspalum
      distichum>Typha orientalis>Hydrilla verticillata. Phosphorus-accumulation ability
      of Paspalum distichum was obviously stronger than Typha orientalis and Hydrilla
      verticillata. The Organic Phosphorus was in aquatic plants dominated by humic
      associated P (Hu-P), which converted to Inorganic Ohosphorus more significantly
      in submerged plants than in emerged plants. The sediment dominated by Paspalum
      distichum abundantly accumulated Organic Phosphorus in the orthophosphate
      monoester fraction. The degradation and mineralization of orthophosphate
      monoester was the important source of high Inorganic Phosphorus concentration and
      net primary productivity in Suoxu River. The Organic Phosphorus derived from
      Typha orientalis and Hydrilla verticillata was dramatically converted to
      Inorganic Phosphorus when the environmental factors varied.

PMID- 25397979
TI  - Cultivation of microalgae in dairy farm wastewater without sterilization.
AB  - The present study investigated the feasibility of cultivating microalgae in dairy
      farm wastewater. The growth of microalgae and the removal rate of the nutrient
      from the wastewater were examined. The wastewater was diluted 20, 10 and 5 times
      before applied to cultivate microalgae. A 5 dilution yielded 0.86 g/L dry weight
      in 6 days with a relative growth rate of 0.28 d(-1), the 10*dilution gave 0.74
      g/L and a relative growth rate of 0.26 d(-1) while the 20*dilution 0.59 g/L and a
      relative growth rate 0.23 d(-1). The nutrients in the wastewater could be removed
      effectively in different diluted dairy wastewater. The greatest dilution (20*)
      showed the removal rates: ammonia, 99.26%; P, 89.92%; COD, 84.18%. A 10*dilution
      removal% was: ammonia 93; P 91 and COD 88. The 5* dilution removal% was: ammonia
      83; P 92; COD 90.

PMID- 25397980
TI  - Negative effects of chelants on soil qualities of five soil series.
AB  - Due to the low phytoavailability of some heavy metals (HMs), a prolonged period
      is required when phytoextraction is used to remove these HMs from contaminated
      soils. The use of chelants and other chemical compounds are often used to
      increase the phytoavailability of the HMs for plant uptake. Negative effects of
      chemical agents on the soil and groundwater have rarely been reported during
      chemical-enhanced phytoextraction. This research applied chelants to various soil
      series with different characteristics to assess their impacts on soil quality.
      The experimental results showed that the application of 5 mmol kg(-1) of all
      chelants had a negative effect on the soil quality. This was especially true for
      electrical conductivity (EC) when diethylene trinitrilo pentaacetic acid (DTPA)
      was used as the chemical extracting agent. 

PMID- 25397981
TI  - Salinity Reduction and Biomass Accumulation in Hydroponic Growth of Purslane
      (Portulaca oleracea).
AB  - In many of the world's semi-arid and arid regions, the increase in demand for
      good quality water associated with the gradual and irreversible salinisation of
      the soil and water have raised the development of techniques that facilitate the
      safe use of brackish and saline waters for agronomic purposes. This study aimed
      to evaluate the salinity reduction of experimental saline solutions through the
      ions uptake capability of purslane (Portulaca oleracea), as well as its biomass
      accumulation. The hydroponic system used contained three different nutrient
      solutions composed of fixed concentrations of macro and micronutrients to which
      three different concentrations of sodium chloride had been added. Two conditions
      were tested, clipped and intact plants. It was observed that despite there being
      a notable removal of magnesium and elevated biomass accumulation, especially in
      the intact plants, purslane did not present the expected removal quantity of
      sodium and chloride. We confirmed that in the research conditions of the present
      study, purslane is a saline-tolerant species but accumulation of sodium and
      chloride was not shown as previously described in the literature. 

PMID- 25397982
TI  - Phytoremediation of metals: a numerical analysis.
AB  - A finite element code was used for investigating the effect of some relevant
      characteristics of a phytoremediation project (crop type and density, presence of
      an irrigation system, soil capping and root depth). The evolution of the plume of
      contamination of Cd2+, Pb2+, and Zn2+ was simulated taking into account reactive
      transport and root processes. The plant contaminant uptake model was previously
      calibrated using data from greenhouse experiments. The simulations adopted
      pedological and climatological data representative of a sub-tropical environment.
      Although the results obtained were specific for the proposed scenario, it was
      observed that, for more mobile contaminants, poor water conditions favor
      stabilization but inhibit plant extraction. Otherwise an irrigation system that
      decreases crop water stress had an opposite effect. For less mobile contaminants,
      the remediation process did not have appreciable advantages. Despite its
      simplifying assumptions, particularly about contaminant sorption in the soil and
      plant system, the numerical analysis provided useful insight for the
      phytoextraction process important in view of field experiments.

PMID- 25397983
TI  - Opportunities for Phytoremediation and Bioindication of Arsenic Contaminated
      Water Using a Submerged Aquatic Plant:Vallisneria natans (lour.) Hara.
AB  - The identification of plants with high arsenic hyperaccumulating efficiency from
      water is required to ensure the successful application of phytoremediation
      technology. Five dominant submerged plant species (Vallisneria natans (Lour.)
      Hara., Potamageton crispus L., Myriophyllum spicatum L., Ceratophyllum demersum
      L. and Hydrilla verticillata (L.f.) Royle) in China were used to determine their
      potential to remove As from contaminated water. V. natans had the highest
      accumulation of As among them. The characteristics of As accumulation,
      transformation and the effect of phosphate on As accumulation in V. natans were
      then further studied. The growth of V. natans was not inhibited even when the As
      concentration reached 2.0 mg L(-1). After 21 d of As treatment, the
      bioconcentration factor (BCF) reached 1300. The As concentration in the
      environment and exposure time are major factors controlling the As concentration
      in V. natans. After being absorbed, As(V) is efficiently reduced to As(III) in
      plants. The synthesis of non-enzymic antioxidants may play an important role
      under As stress and increase As detoxication. In addition, As(V) uptake by V.
      natans was negatively correlated with phosphate (P) uptake when P was
      sufficiently supplied. As(V) is probably taken up via P transporters in V.
      natans.

PMID- 25397984
TI  - Hyperaccumulator oilcake manure as an alternative for chelate-induced
      phytoremediation of heavy metals contaminated alluvial soils.
AB  - The ability of hyperaccumulator oilcake manure as compared to chelates was
      investigated by growing Calendula officinalis L for phytoremediation of cadmium
      and lead contaminated alluvial soil. The combinatorial treatment T6 [2.5 g kg(-1)
      oilcake manure+5 mmol kg(-1) EDDS] caused maximum cadmium accumulation in root,
      shoot and flower up to 5.46, 4.74 and 1.37 mg kg(-1) and lead accumulation up to
      16.11, 13.44 and 3.17 mg kg(-1), respectively at Naini dump site, Allahabad (S3).
      The treatment showed maximum remediation efficiency for Cd (RR=0.676%) and Pb
      (RR=0.202%) at Mumfordganj contaminated site (S2). However, the above parameters
      were also observed at par with the treatment T5 [2.5 g kg(-1) oilcake manure +2 g
      kg(-1) humic acid]. Applied EDDS altered chlorophyll-a, chlorophyll-b, and
      carotene contents of plants while application of oilcake manure enhanced their
      contents in plant by 3.73-8.65%, 5.81-17.65%, and 7.04-17.19%, respectively. The
      authors conclude that Calendula officinalis L has potential to be safely grown in
      moderately Cd and Pb-contaminated soils and application of hyperaccumulator
      oilcake manure boosts the photosynthetic pigments of the plant, leading to
      enhanced clean-up of the cadmium and lead-contaminated soils. Hence, the
      hyperaccumulator oilcake manure should be preferred over chelates for sustainable
      phytoremediation through soil-plant rhizospheric process.

PMID- 25397985
TI  - Uptake and distribution of stable strontium in 26 cultivars of three crop
      species: oats, wheat, and barley for their potential use in phytoremediation.
AB  - The main objective of this study was to investigate the accumulation and
      distribution of strontium (Sr) in 26 cultivars of wheat (Triticum aestivum L.),
      husk oat (Avena sativa L) and naked oat (Avena nuda), and barley (Hordeum vulgare
      L.) for their potential use in phytoremediation.Sr levels had no effect on the
      accumulation of shoot biomass at tillering or at maturity. Mean shoot Sr
      concentration of naked oat and barley at tillering was significantly (P<0.05)
      higher than that of wheat; Neimengkeyimai-1, a naked oat cultivar, had the
      highest Sr concentrations. At maturity, of four naked oat cultivars,
      Neimengkeyimai-1 had the highest Sr content at all measured Sr levels. Leaves had
      the highest Sr concentrations, followed by roots and straw, and then grain with
      the lowest. Mean enrichment coefficients from soil to shoots ranged from 0.521 to
      1.343; the percentage of stable Sr removed from the soil to the shoots at harvest
      time was more than 1.4% after 120 days. Neimengkeyimai-1 could be used as a model
      for further research to find more effective cultivars; and naked oat plants could
      be selected for phytoremediation to clean up contaminated soil.

PMID- 25397986
TI  - Zinc Accumulation and Tolerance in Solanum nigrum are Plant Growth Dependent.
AB  - Zinc tolerance, accumulation, and organic acid production by Solanum nigrum, a
      known Zn accumulator, was studied during pre- and post-flowering stages of
      development. The plants, when challenged with Zn concentrations lethal to
      plantlets, showed an increase in tolerance from pre-flowering to post-flowering,
      which was accompanied by a reduction of Zn translocation to the aerial plant
      parts. Treatment with Zn induced a differential response in organic acids
      according to the plant organ and developmental stage. In the roots, where Zn
      concentrations were similar in pre- and post-flowering plants, a general decrease
      in organic acid in pre-flowering roots contrasted with the increase observed in
      post-flowering plants. In the stems, Zn induced a generalized increase in organic
      acids at both growth stages while in the leaves, a slight increase in malic and
      shikimic was observed in pre-flowering plants and only shikimic acid levels were
      significantly increased in post-flowering plants. This work shows that Zn
      accumulation and tolerance in S. nigrum vary during plant development--an
      observation that may be important to improve the efficiency of phytoremediation
      approaches. Furthermore, the data suggest the involvement of specific organic
      acids in this response.

PMID- 25397987
TI  - Physiological Responses and Tolerance Mechanisms to Cadmium in Conyza canadensis.
AB  - Experiments were conducted to examine the effects of different concentrations of
      Cd on the performance of the Cd accumulator Conyza canadensis. Cd accumulation in
      roots and leaves (roots>leaves) increased with increasing Cd concentration in
      soil. High Cd concentration inhibited plant growth, increased the membrane
      permeability of leaves, and caused a significant decline in plant height and
      chlorophyll [chlorophyll (Chl) a, Chl b, and total Chl] content. Leaf
      ultrastructural analysis of spongy mesophyllic cells revealed that excessive Cd
      concentrations cause adverse effects on the chloroplast and mitochondrion
      ultrastructures of C. canadensis. However, the activities of antioxidant enzymes,
      such as superoxide dismutase, catalase, peroxidase, total non-protein SH
      compounds, glutathione, and phytochelatin (PC) concentrations, showed an overall
      increase. Specifically, the increase in enzyme activities demonstrated that the
      antioxidant system may play an important role in eliminating or alleviating the
      toxicity of Cd in C. canadensis. Furthermore, results demonstrate that PC
      synthesis in plant cells is related to Cd concentration and that PC production
      levels in plants are related to the toxic effects caused by soil Cd level. These
      findings demonstrate the roles played by these compounds in supporting Cd
      tolerance in C. canadensis.

PMID- 25397988
TI  - Heavy Metal Uptakes by Myriophyllum verticillatum from Two Environmental
      Matrices: The Water and the Sediment.
AB  - To determine the preferred elements of the benthic plant Myriophyllum
      verticillatum, changes in the element concentrations in the plant were
      investigated in laboratory condition. The reactor was fed with synthetically
      contaminated water consisting of 2*10(-6) M of the heavy metals Fe, Cr, Zn, Ni,
      and Cu for 1060 hours. The elements that were preferentially taken up by the
      tested plant body were evaluated with respect to translocation factor, bio
      concentration factor, and the amounts of partial elements and relative uptakes.
      Both the changing physical properties of the aqueous solution in the reactor
      during the experiment and the growth of the plant were tested using a two-sample
      t-test. The Zn and Cu levels in the combination of the leaves and stems were
      found to be significantly higher than the levels in the roots at the end of the
      trial. Based on the partial amount of each element, the affinity of the plant for
      different elements was found to follow the order of Ca>Fe>Mn. Scanning electron
      microscope (SEM) analyses of the plant bodies indicated that these elements were
      located both inside the organs and on the surface of the tissues alone or with
      microorganisms such as diatoms.

PMID- 25397989
TI  - Cadmium accumulation by jack-bean and sorghum in hydroponic culture.
AB  - Among the technologies used to recuperate cadmium (Cd) contaminated soils,
      phytoextraction are particularly important, where the selection of suitable
      plants is critical to the success of the soil remediation. Thus, the objectives
      of this study were to evaluate the responses of jack-bean and sorghum to Cd
      supply and to quantify Cd accumulation by these species grown in hydroponic
      culture. The plants were subjected to 0, 15, 30, or 60 MUmol Cd L(-1) in the
      nutrient solution, and gas exchange, plant growth and Cd accumulation were
      measured at 25 days after starting Cd treatments. The Cd supply severely reduced
      growth of shoots and roots in both species. In jack-bean, Cd decreased
      photosynthesis by 56-86%, stomatal conductance by 59-85% and transpiration by 48
      80%. The concentrations and amounts of Cd accumulated in the plant tissues were
      proportional to the metal supply in the nutrient solution. Sorghum was more
      tolerant than jack-bean to Cd toxicity, but the latter showed a greater metal
      concentration and accumulation in the shoot. Therefore, jack-bean would be more
      suitable than sorghum for use in Cd phytoremediation programs based on
      phytoextraction. 

PMID- 25397990
TI  - Fresh versus frozen engineered bone-ligament-bone grafts for sheep anterior
      cruciate ligament repair.
AB  - Surgical intervention is often required to restore knee instability in patients
      with anterior cruciate ligament (ACL) injury. The most commonly used grafts for
      ACL reconstruction are tendon autografts or allografts. These current options,
      however, have shown failure rates requiring revision and continued instability in
      the long term. The mismatched biomechanical properties of the current tendon
      grafts compared with native ACL tissue are thought to contribute to these poor
      outcomes and potential risk of early onset osteoarthritis. As a possible solution
      to these issues, our laboratory has fabricated tissue-engineered ligament
      constructs that exhibit structural and functional properties similar to those of
      native ACL tissue after 6 months implantation. In addition, these tissue
      engineered grafts achieve vascular and neural development that exceeds those of
      patellar tendon grafts. However, the utility of our tissue-engineered grafts is
      limited by the labor-intensive method required to produce the constructs and the
      need to use the constructs fresh, directly from the cell culturing system.
      Ideally, these constructs would be fabricated and stored until needed. Thus, in
      this study, we investigated the efficacy of freezing our tissue-engineered
      constructs as a method of preservation before use for ACL reconstruction. We
      hypothesized that frozen constructs would have similar histological and
      biomechanical outcomes compared with our fresh model. Our results showed that 6
      months postimplantation as an ACL replacement graft, both our tissue-engineered
      fresh and frozen grafts demonstrated similar mechanical and histological
      outcomes, indicating that freezing is a suitable method for preserving and
      storing our graft before ACL reconstruction. The ability to use frozen constructs
      significantly increases the versatility of our graft technology expanding the
      clinical utility of our graft. 

PMID- 25397991
TI  - Positive role of surface defects on carbon nanotube cathodes in overpotential and
      capacity retention of rechargeable lithium-oxygen batteries.
AB  - Surface defects on carbon nanotube cathodes have been artificially introduced by
      bombardment with argon plasma. Their roles in the electrochemical performance of
      rechargeable Li-O2 batteries have been investigated. In batteries with
      tetraethylene glycol dimethyl ether (TEGDME)- and N-methyl-N-propylpiperidinium
      bis(trifluoromethansulfonyl)imide (PP13TFSI)-based electrolytes, the defects
      increase the number of nucleation sites for the growth of Li2O2 particles and
      reduce the size of the formed particles. This leads to increased discharge
      capacity and reduced cycle overpotential. However, in the former batteries, the
      hydrophilic surfaces induced by the defects promote carbonate formation, which
      imposes a deteriorating effect on the cycle performance of the Li-O2 batteries.
      In contrast, in the latter case, the defective cathodes promote Li2O2 formation
      without enhancing formation of carbonates on the cathode surfaces, resulting in
      extended cycle life. This is most probably attributable to the passivation effect
      on the functional groups of the cathode surfaces imposed by the ionic liquid.
      These results indicate that defects on carbon surfaces may have a positive effect
      on the cycle performance of Li-O2 batteries if they are combined with a helpful
      electrolyte solvent such as PP13TFSI.

PMID- 25397992
TI  - Nannozinones and sorazinones, unprecedented pyrazinones from myxobacteria.
AB  - Nannozinones A (1) and B (2) were discovered as metabolites of the recently
      isolated Nannocystis pusilla strain MNa10913 belonging to the poorly studied
      myxobacterial family Nannocystaceae. In contrast, the structurally related
      sorazinones A (5) and B (6) were isolated from Sorangium cellulosum strain
      Soce895, which was known as the producer of the antibiotic thuggacin A. The
      extract also contained methyl indole-3-carboxylate (4). HRESIMS and (1)H, (13)C,
      and (15)N NMR spectroscopy revealed the structures of nannozinones A (1) and B
      (2) as unusual dihydropyrrolo- and pyrrolopyrazinone derivatives, while
      sorazinone A (5) was characterized as an aromatic diketopiperazine and sorazinone
      B (6) as a dibenzyl 2(1H)-pyrazinone derivative. While the dihydropyrrolo
      derivative nannozinone A (1) showed weak antibacterial and antifungal activity,
      nannozinone B (2) inhibited the growth of cell cultures with IC50 values between
      2.44 and 16.9 MUM. The nannochelin A iron complex (3), which was isolated besides
      1 and 2, was even more active, with IC50 values between 0.05 and 1.95 MUM. On the
      other hand, the indole 4 and sorazinones 5 and 6 did not show any significant
      cytotoxicity and only weak activity against the Gram-positive Nocardia sp. 

PMID- 25397993
TI  - Concentration-Dependent Vascularization of Adipose Stromal Vascular Fraction
      Cells.
AB  - Adipose-derived stromal vascular fraction (SVF) cells have been shown to self
      associate to form vascular structures under both in vitro and in vivo conditions.
      The angiogenic (new vessels from existing vessels) and vasculogenic (new vessels
      through self-assembly) potential of the SVF cell population may provide a cell
      source for directly treating (i.e., point of care without further cell isolation)
      ischemic tissues. However the correct dosage of adipose SVF cells required to
      achieve a functional vasculature has not been established. Accordingly, in vitro
      and in vivo dose response assays were performed evaluating the SVF cell
      vasculogenic potential. Serial dilutions of freshly isolated rat adipose SVF
      cells were plated on growth factor reduced Matrigel and vasculogenesis, assessed
      as cellular tube-like network assembly, was quantified after 3 days of culture.
      This in vitro vasculogenesis assay indicated that rat SVF cells reached maximum
      network length at a concentration of 2.5 * 10(5) cells/ml and network maintained
      at the higher concentrations tested. The same concentrations of rat and human SVF
      cells were used to evaluate vasculogenesis in vivo. SVF cells were incorporated
      into collagen gels and subcutaneously implanted into Rag1 immunodeficient mice.
      The 3D confocal images of harvested constructs were evaluated to quantify dose
      dependency of SVF cell vasculogenesis potential. Rat- and human-derived SVF cells
      yielded a maximum vasculogenic potential at 1 * 10(6) and 4 * 10(6) cells/ml,
      respectively. No adverse reactions (e.g., toxicity, necrosis, tumor formation)
      were observed at any concentration tested. In conclusion, the vasculogenic
      potential of adipose-derived SVF cell populations is dose dependent. 

PMID- 25397994
TI  - Understanding the role of age in HIV disclosure rates and patterns for HIV
      infected children in southwestern Uganda.
AB  - Highly active antiretroviral therapy has enabled HIV-infected children to survive
      into adolescence and adulthood, creating need for their own HIV diagnosis
      disclosure. Disclosure has numerous social and medical benefits for the child and
      family; however, disclosure rates tend to be low, especially in developing
      countries, and further understanding of the barriers is needed. This study
      describes the patterns and correlates of disclosure among HIV-infected children
      in southwestern Uganda. A cross-sectional study was conducted in a referral
      hospital pediatric HIV clinic between February and April 2012. Interviews were
      administered to caregivers of HIV-infected children aged 5-17 years. Data
      collected included socio-demographic characteristics of the child and caregiver,
      reported disclosure status, and caregivers' reasons for full disclosure or non
      full disclosure of HIV status to their children. Bivariate and multivariate
      analysis was done to establish the socio-demographic correlates of disclosure.
      Caregivers provided data for 307 children; the median age was eight years
      (interquartile range [IQR] 7-11) and 52% were males. Ninety-five (31%) children
      had received full disclosure (48% of whom were >12 years), 22 children (7%) had
      received partial disclosure, 39 (13%) misinformation, and 151 (49%) no
      disclosure. Full disclosure was significantly more prevalent among the 9-11 and
      12- to 17-year-olds compared to 5- to 8-year-olds (p-value < 0.001). The most
      frequently stated reason for disclosure was the hope that disclosure would
      improve medication adherence; the most frequently stated reason for nondisclosure
      was the belief that the child was too young to understand his/her illness. There
      was an inverse relationship between age and full disclosure and partial
      disclosure was rare across all age groups, suggesting a pattern of rapid, late
      disclosure. Disclosure programs should emphasize the importance of gradual
      disclosure, starting at younger ages, to maximize the benefits to the child and
      caregiver. 

PMID- 25397995
TI  - Nutritional status in patients with cutaneous leishmaniasis and a study of the
      effects of zinc supplementation together with antimony treatment.
AB  - BACKGROUND: The role of micronutrient status for the incidence and clinical
      course of cutaneous leishmaniasis is not much studied. Still zinc supplementation
      in leishmaniasis has shown some effect on the clinical recovery, but the evidence
      in humans is limited. OBJECTIVE: To compare biochemical nutritional status in
      cutaneous leishmaniasis patients with that in controls and to study the effects
      of zinc supplementation for 60 days. DESIGN: Twenty-nine patients with cutaneous
      leishmaniasis were treated with antimony for 20 days. Fourteen of them got 45 mg
      zinc daily and 15 of them got placebo. Biomarkers of nutritional and inflammatory
      status and changes in size and characteristics of skin lesions were measured.
      RESULTS: The level of transferrin receptor was higher in patients than in
      controls but otherwise no differences in nutritional status were found between
      patients and controls. No significant effects of zinc supplementation on the
      clinical recovery were observed as assessed by lesion area reduction and
      characteristics or on biochemical parameters. CONCLUSIONS: It is concluded that
      nutritional status was essentially unaffected in cutaneous leishmaniasis and that
      oral zinc supplementation administered together with intramuscular injection of
      antimony had no additional clinical benefit.

PMID- 25397996
TI  - Suvorexant: something new for sleep?
AB  - Orexin, also called hypocretin, is a neuropeptide that acts on central nervous
      system receptors to promote arousal. Suvorexant, its receptor antagonist,
      generates interest as a medication to treat insomnia. Suvorexant helps in
      decreasing wakefulness by counteracting orexin activity. Its low side effect
      potential may offer considerable benefit. Compared with other sleep aids,
      diminished drowsiness and less cognitive dysfunction is an advantage. Now
      approved for clinical use, an apparent lack of rebound insomnia or drug
      dependence potential might make suvorexant a good choice pharmacotherapy for
      patients with insomnia. 

PMID- 25397997
TI  - Effects of Two Concussions on the Neuropsychological Functioning and Symptom
      Reporting of High School Athletes.
AB  - To assess the effects of two sports-related concussions on neuropsychological
      functioning and symptom reporting, the Immediate Post-Concussion Assessment and
      Cognitive Testing (ImPACT) was administered to 483 high school athletes. Three
      groups of athletes were determined based on the number of previous concussions:
      no concussion (n = 409), 1 concussion (n = 58), and 2 concussions (n = 16). The
      results showed that the three groups did not differ in terms of their ImPACT
      composite scores (Verbal Memory, Visual Memory, Reaction Time, and Processing
      Speed) and the Total Symptom Score. As there are only a few studies that have
      reported the sequelae of 2 concussions in high school athletes, it is premature
      to declare that a repeated concussion does not have persistent neurocognitive
      effects on high school athletes. 

PMID- 25397998
TI  - Evaluation of the sensitivity and specificity of an enzyme-linked immunosorbent
      assay for diagnosing brucellosis in African buffalo (Syncerus caffer).
AB  - Brucellosis is a disease of veterinary and public health importance worldwide. In
      sub-Saharan Africa, where the bacterium Brucella abortus has been identified in
      several free-ranging wildlife species, successful disease control may be
      dependent on accurate detection in wildlife reservoirs, including African buffalo
      (Syncerus caffer). We estimated the sensitivity and specificity of a commercial
      enzyme-linked immunosorbent assay (ELISA) (IDEXX Brucellosis Serum Ab test, IDEXX
      Laboratories, Westbrook, Maine, USA) for B. abortus based on a data set of 571
      serum samples from 258 buffalo in the Kruger National Park, South Africa. We
      defined a pseudogold standard test result as those buffalo that were consistently
      positive or negative on two additional serologic tests, namely, the rose bengal
      test (RBT) and the complement fixation test (CFT). The ELISA's cutoff value was
      selected using receiver operating characteristics analysis, the pseudogold
      standard, and a threshold criterion that maximizes the total sensitivity and
      specificity. Then, we estimated the sensitivity and specificity of all three
      tests using Bayesian inference and latent class analysis. The ELISA had an
      estimated sensitivity of 0.928 (95% Bayesian posterior credibility interval [95%
      BCI] = 0.869-0.974) and specificity of 0.870 (95% BCI = 0.836-0.900). Compared
      with the ELISA, the RBT had a higher estimated sensitivity of 0.986 (95% BCI =
      0.928-0.999), and both the RBT and CFT had higher specificities, estimated to be
      0.992 (95% BCI = 0.971-0.996) and 0.998 (95% BCI = 0.992-0.999), respectively.
      Therefore, no single serologic test perfectly detected the antibody. However,
      after adjustment of cutoff values for South African conditions, the IDEXX
      Brucellosis Serum Ab Test may be a valuable additional screening test for
      brucellosis in Kruger National Park's African buffalo.

PMID- 25397999
TI  - Involvement of two genetic lineages of Sarcoptes scabiei mites in a local mange
      epizootic of wild mammals in Japan.
AB  - Similar to wild mammals on the continents, mange caused by the mange mite,
      Sarcoptes scabiei (Acari: Sarcoptidae) is spreading in wild mammals in most of
      Japan. We collected crusted or alopetic skin from 120 raccoon dogs (Nyctereutes
      procyonoides viverrinus), three raccoons (Procyon lotor), six Japanese badgers
      (Meles anakuma), one Japanese marten (Martes melampus), one stray dog (Canis
      lupus familiaris), four wild boars (Sus scrofa leucomystax), and one Japanese
      serow (Capricornis crispus), mainly in an area where mangy wild animals have been
      increasingly noted in the past 4 yr. The second internal transcribed spacer
      (ITS2) region of the ribosomal RNA gene and the partial 16S and cytochrome c
      oxidase subunit I (cox-1) genes of mitochondrial DNA (mtDNA) were characterized
      in these skin samples. The ITS2 sequencing (404 base pairs [bp]) identified the
      causative mite for mangy skin lesions of 128 animals as S. scabiei, regardless of
      host origin. The cat mite (Notoedres cati) was the cause in one raccoon dog and
      one raccoon. Most mites had almost identical ITS2 nucleotide sequences to those
      recorded in a variety of mammals worldwide. Partial 16S and cox-1 fragments of
      mtDNA amplified and sequenced successfully (331 bp and 410 bp, respectively)
      showed an identical nucleotide sequence except for one site (C vs. T) for the
      former and four sites (G, C, C, C vs. A, T, T, T, respectively) for the latter
      fragment. These substitutions were always synchronized, with the two
      mitochondrial DNA haplotypes (i.e., C/GCCC and T/ATTT) appearing to separately
      colonize in geographic units. The T/ATTT haplotype fell into a clade where animal
      derived mites worldwide dominated, whereas the C/GCCC haplotype formed a
      geographic branch unique to Japanese isolates. These results suggest that
      heterologous populations of monospecific S. scabiei are expanding their
      populations and distributions regardless of host species in an apparently local
      mange epizootic of wild mammals in Japan.

PMID- 25398000
TI  - Familiarity breeds contempt: combining proximity loggers and GPS reveals female
      white-tailed deer (Odocoileus virginianus) avoiding close contact with neighbors.
AB  - Social interactions can influence infectious disease dynamics, particularly for
      directly transmitted pathogens. Therefore, reliable information on contact
      frequency within and among groups can better inform disease modeling and
      management. We compared three methods of assessing contact patterns: (1) space
      use overlap (volume of interaction [VI]), (2) direct contact rates measured by
      simultaneous global positioning system (GPS) locations (<10 m apart), and (3)
      direct contact rates measured by proximity loggers (PLs; 1-m detection) among
      female white-tailed deer (Odocoileus virginianus). We calculated the PL?GPS
      contact ratios to see whether both devices reveal similar contact patterns and
      thus predict similar pathogen transmission patterns. Contact rates measured by
      GPS and PLs were similarly high for two within-group dyads (pairs of deer in the
      same social groups). Dyads representing separate but neighboring groups (high VI)
      had PL?GPS contact ratios near zero, whereas dyads further apart (intermediate
      VI) had higher PL?GPS contact ratios. Social networks based on PL contacts showed
      the fewest connected individuals and lowest mean centrality measures; network
      metrics were intermediate when based on GPS contacts and greatest when based on
      VI. Thus, the VI network portrayed animals to be more uniformly and strongly
      connected than did the PL network. We conclude that simultaneous GPS locations,
      compared with PLs, substantially underestimate the impact of group membership on
      direct contact rates of female deer and make networks appear more connected. We
      also present evidence that deer coming within the general vicinity of each other
      are less likely to come in close contact if they are in neighboring social groups
      than deer whose home ranges overlap little if at all. Combined, these results
      provide evidence that direct transmission of disease agents among female and
      juvenile white-tailed deer is likely to be constrained both spatially and by
      social structure, more so than GPS data alone would suggest.

PMID- 25398001
TI  - Lithiation-induced zinc clustering of Zn3, Zn12, and Zn18 units in Zintl-like
      Ca~30Li3+xZn60-x (x = 0.44-1.38).
AB  - Zinc clusters are not common for binary intermetallics with relatively low zinc
      content, but this work shows that zinc clustering can be triggered by lithiation,
      as exemplified by Ca(~30)Li(3+x)Zn(60-x), P6/mmm, Z = 1, which can be directly
      converted from CaZn(2). Two end members of the solid solution (x = 0.44 and 1.38)
      were established and structurally characterized by single-crystal X-ray
      diffraction analyses: Ca(30)Li(3.44(6))Zn(59.56(6)), a = 15.4651(9) A, c =
      9.3898(3) A; Ca(30.45(2))Li(4.38(6))Zn(58.62(6)), a = 15.524(3) A, c = 9.413(2)
      A. The structures of Ca(~30)Li(3+x)Zn(60-x) feature a condensed anionic network
      of Zn(3) triangles, lithium-centered Zn(12) icosahedra, and arachno-(Zn,Li)18
      tubular clusters that are surrounded respectively by Ca(14), Ca(20), and Ca(30)
      polyhedra. These polyhedra share faces and form a clathrate-like cationic
      framework. The specific occupation of lithium in the structure is consistent with
      theoretical "coloring" analyses. Analysis by the linear muffin-tin orbital (LMTO)
      method within the atomic sphere approximation reveals that Ca(~30)Li(3+x)Zn(60-x)
      is a metallic, Zintl-like phase with an open-shell electronic structure. The
      contribution of Ca-Zn polar covalent interactions is about 41%.

PMID- 25398002
TI  - A longitudinal study of sick building syndrome (SBS) among pupils in relation to
      SO2, NO2, O3 and PM10 in schools in China.
AB  - There are fewer longitudinal studies from China on symptoms as described for the
      sick building syndrome (SBS). Here, we performed a two-year prospective study and
      investigated associations between environmental parameters such as room
      temperature, relative air humidity (RH), carbon dioxide (CO2), nitrogen dioxide
      (NO2), sulphur dioxide (SO2), ozone (O3), particulate matter (PM10), and health
      outcomes including prevalence, incidence and remission of SBS symptoms in junior
      high schools in Taiyuan, China. Totally 2134 pupils participated at baseline, and
      1325 stayed in the same classrooms during the study period (2010-2012). The
      prevalence of mucosal symptoms, general symptoms and symptoms improved when away
      from school (school-related symptoms) was 22.7%, 20.4% and 39.2%, respectively,
      at baseline, and the prevalence increased during follow-up (P<0.001). At
      baseline, both indoor and outdoor SO2 were found positively associated with
      prevalence of school-related symptoms. Indoor O3 was shown to be positively
      associated with prevalence of skin symptoms. At follow-up, indoor PM10 was found
      to be positively associated with new onset of skin, mucosal and general symptoms.
      CO2 and RH were positively associated with new onset of mucosal, general and
      school-related symptoms. Outdoor SO2 was positively associated with new onset of
      skin symptoms, while outdoor NO2 was positively associated with new onset of
      skin, general and mucosal symptoms. Outdoor PM10 was found to be positively
      associated with new onset of skin, general and mucosal symptoms as well as school
      related symptoms. In conclusion, symptoms as described for SBS were commonly
      found in school children in Taiyuan City, China, and increased during the two
      year follow-up period. Environmental pollution, including PM10, SO2 and NO2,
      could increase the prevalence and incidence of SBS and decrease the remission
      rate. Moreover, parental asthma and allergy (heredity) and pollen or pet allergy
      (atopy) can be risk factors for SBS. 

PMID- 25398003
TI  - Meta-analysis of gene expression signatures reveals hidden links among diverse
      biological processes in Arabidopsis.
AB  - The model plant Arabidopsis has been well-studied using high-throughput genomics
      technologies, which usually generate lists of differentially expressed genes
      under various conditions. Our group recently collected 1065 gene lists from 397
      gene expression studies as a knowledgebase for pathway analysis. Here we
      systematically analyzed these gene lists by computing overlaps in all-vs.-all
      comparisons. We identified 16,261 statistically significant overlaps, represented
      by an undirected network in which nodes correspond to gene lists and edges
      indicate significant overlaps. The network highlights the correlation across the
      gene expression signatures of the diverse biological processes. We also
      partitioned the main network into 20 sub-networks, representing groups of highly
      similar expression signatures. These are common sets of genes that were co
      regulated under different treatments or conditions and are often related to
      specific biological themes. Overall, our result suggests that diverse gene
      expression signatures are highly interconnected in a modular fashion. 

PMID- 25398004
TI  - The effect of aging on the specialized conducting system: a telemetry ECG study
      in rats over a 6 month period.
AB  - Advanced age alone appears to be a risk factor for increased susceptibility to
      cardiac arrhythmias. We previously observed in the aged rat heart that sinus
      rhythm ventricular activation is delayed and characterized by abnormal epicardial
      patterns although conduction velocity is normal. While these findings relate to
      an advanced stage of aging, it is not yet known when and how ventricular
      electrical impairment originates and which is the underlying substrate. To
      address these points, we performed continuous telemetry ECG recordings in freely
      moving rats over a six-month period to monitor ECG waveform changes, heart rate
      variability and the incidence of cardiac arrhythmias. At the end of the study, we
      performed in-vivo multiple lead epicardial recordings and histopathology of
      cardiac tissue. We found that the duration of ECG waves and intervals gradually
      increased and heart rate variability gradually decreased with age. Moreover, the
      incidence of cardiac arrhythmias gradually increased, with atrial arrhythmias
      exceeding ventricular arrhythmias. Epicardial multiple lead recordings confirmed
      abnormalities in ventricular activation patterns, likely attributable to distal
      conducting system dysfunctions. Microscopic analysis of aged heart specimens
      revealed multifocal connective tissue deposition and perinuclear myocytolysis in
      the atria. Our results demonstrate that aging gradually modifies the terminal
      part of the specialized cardiac conducting system, creating a substrate for
      increased arrhythmogenesis. These findings may open new therapeutic options in
      the management of cardiac arrhythmias in the elderly population. 

PMID- 25398005
TI  - Differential control of interleukin-6 mRNA levels by cellular distribution of YB
      1.
AB  - Cytokine production is essential for innate and adaptive immunity against
      microbial invaders and must be tightly controlled. Cytokine messenger RNA (mRNA)
      is in constant flux between the nucleus and the cytoplasm and in transcription,
      splicing, or decay; such processes must be tightly controlled. Here, we report a
      novel function of Y-box-binding protein 1 (YB-1) in modulating interleukin-6 (IL
      6) mRNA levels in a cell type-specific manner. In lipopolysaccharide (LPS)
      stimulated macrophages, YB-1 interacts with IL-6 mRNA and actively transports it
      to the extracellular space by YB-1-enriched vesicles, resulting in the proper
      maintenance of intracellular IL-6 mRNA levels. YB-1 secretion occurs in a cell
      type-specific manner. Whereas macrophages actively secret YB-1, dendritic cells
      maintain it predominantly in the cytoplasm even in response to LPS. Intracellular
      YB-1 has the distinct function of regulating IL-6 mRNA stability in dendritic
      cells. Moreover, because LPS differentially regulates the expression of histone
      deacetylase 6 (HDAC6) in macrophages and dendritic cells, this stimulus might
      control YB-1 acetylation differentially in both cell types. Taken together, these
      results suggest a unique feature of YB-1 in controlling intracellular IL-6 mRNA
      levels in a cell type-specific manner, thereby leading to functions that are
      dependent on the extracellular and intracellular distribution of YB-1. 

PMID- 25398007
TI  - Regional difference in sex steroid action on formation of morphological sex
      differences in the anteroventral periventricular nucleus and principal nucleus of
      the bed nucleus of the stria terminalis.
AB  - Sex steroid action is critical to form sexually dimorphic nuclei, although it is
      not fully understood. We previously reported that masculinization of the
      principal nucleus of the bed nucleus of the stria terminalis (BNSTp), which is
      larger and has more neurons in males than in females, involves aromatized
      testosterone that acts via estrogen receptor-alpha (ERalpha), but not estrogen
      receptor-beta (ERbeta). Here, we examined sex steroid action on the formation of
      the anteroventral periventricular nucleus (AVPV) that is larger and has more
      neurons in females. Morphometrical analysis of transgenic mice lacking aromatase,
      ERalpha, or ERbeta genes revealed that the volume and neuron number of the male
      AVPV were significantly increased by deletion of aromatase and ERalpha genes, but
      not the ERbeta gene. We further examined the AVPV and BNSTp of androgen receptor
      knockout (ARKO) mice. The volume and neuron number of the male BNSTp were smaller
      in ARKO mice than those in wild-type mice, while no significant effect of ARKO
      was found on the AVPV and female BNSTp. We also examined aromatase, ERalpha, and
      AR mRNA levels in the AVPV and BNSTp of wild-type and ARKO mice on embryonic day
      (ED) 18 and postnatal day (PD) 4. AR mRNA in the BNSTp and AVPV of wild-type mice
      was not expressed on ED18 and emerged on PD4. In the AVPV, the aromatase mRNA
      level was higher on ED18, although the ERalpha mRNA level was higher on PD4
      without any effect of AR gene deletion. Aromatase and ERalpha mRNA levels in the
      male BNSTp were significantly increased on PD4 by AR gene deletion. These results
      suggest that estradiol signaling via ERalpha during the perinatal period and
      testosterone signaling via AR during the postnatal period are required for
      masculinization of the BNSTp, whereas the former is sufficient to defeminize the
      AVPV. 

PMID- 25398009
TI  - Prevalence and psychosocial correlates of depressive symptoms in urban Chinese
      women during midlife.
AB  - OBJECTIVE: Depression is common in women with much research focusing on hormonal
      changes and menopausal symptoms but with little exploration of psychosocial
      problems in midlife. This study investigates the prevalence of clinically
      relevant depressive symptoms in midlife Chinese women and its association with
      psychosocial factors. METHODS: A cross-sectional, community-based household
      survey of women aged 45 to 64 years of age was conducted in Hong Kong from
      September 2010 to March 2011. The structured questionnaire included demographic
      data, educational status, marital status and household income, as well as
      perceived current stressful events and significant life events in the past 12
      months. Information on clinically relevant depressive symptoms was measured by
      the validated chinese Patient Health Questionnaire (PHQ-9). RESULTS: A total of
      402 participants were recruited in the study period. Of the 393 women who
      completed the questionnaire, the prevalence of clinically relevant depressive
      symptoms (PHQ-9 score?10) was 11.0%. In multiple regression analysis, being
      single/divorced/separated/widowed, having an educational level of primary school
      level or below, having multiple chronic diseases, loss of hobby or loss of close
      social support in the past 12 months in midlife were associated with clinically
      relevant depressive symptoms. CONCLUSIONS: Correlates of clinically relevant
      depressive symptoms in midlife Chinese women can be used to identify those at
      increased risk and potentiate further studies to explore early psychosocial and
      community interventions.

PMID- 25398010
TI  - The homeostatic chemokine CCL21 predicts mortality in aortic stenosis patients
      and modulates left ventricular remodeling.
AB  - BACKGROUND: CCL21 acting through CCR7, is termed a homeostatic chemokine. Based
      on its role in concerting immunological responses and its proposed involvement in
      tissue remodeling, we hypothesized that this chemokine could play a role in
      myocardial remodeling during left ventricular (LV) pressure overload. METHODS AND
      RESULTS: Our main findings were: (i) Serum levels of CCL21 were markedly raised
      in patients with symptomatic aortic stenosis (AS, n = 136) as compared with
      healthy controls (n = 20). (ii) A CCL21 level in the highest tertile was
      independently associated with all-cause mortality in these patients. (iii)
      Immunostaining suggested the presence of CCR7 on macrophages, endothelial cells
      and fibroblasts within calcified human aortic valves. (iv). Mice exposed to LV
      pressure overload showed enhanced myocardial expression of CCL21 and CCR7 mRNA,
      and increased CCL21 protein levels. (v) CCR7-/- mice subjected to three weeks of
      LV pressure overload had similar heart weights compared to wild type mice, but
      increased LV dilatation and reduced wall thickness. CONCLUSIONS: Our studies,
      combining experiments in clinical and experimental LV pressure overload, suggest
      that CCL21/CCR7 interactions might be involved in the response to pressure
      overload secondary to AS.

PMID- 25398011
TI  - Earlier initiation and use of a greater number of iron-folic acid supplements
      during pregnancy prevents early neonatal deaths in Nepal and Pakistan.
AB  - INTRODUCTION: Early neonatal deaths account for 75% of neonatal deaths globally.
      Antenatal iron-folic acid (IFA) supplementation has significantly reduced the
      risk of early neonatal deaths in China and Indonesia. We investigated the impact
      of antenatal IFA supplements on the risk of early neonatal deaths in Nepal and
      Pakistan during the last decade. METHODS: Data from the most recent singleton
      live-births of 8,186 from two Nepal Demographic and Health Surveys (DHS) and
      13,034 from two Pakistan DHS were selected for the current study. The primary
      outcome was early neonatal deaths and the main study variable was antenatal IFA
      supplementation. Analyses used multivariate Cox proportional regression, adjusted
      for the cluster sampling design and for 18 potential confounders. FINDINGS: The
      adjusted risk of early neonatal deaths was significantly reduced by 51% (aHR =
      0.49, 95% CI = 0.32-0.75) in Nepal and 23% (aHR = 0.77, 95% CI = 0.59-0.99) in
      Pakistan with any use of IFA compared to none. When IFA supplementation started
      at or before the 5th month of pregnancy, the adjusted risk of early neonatal
      mortality was significantly reduced by 53% in Nepal, and 28% in Pakistan,
      compared to no IFA. When >90 IFA supplements were used and started at or before
      5th months, the adjusted risk of early neonatal deaths was significantly reduced
      by 57% in Nepal, and 45% in Pakistan. In Nepal 4,600 and in Pakistan 75,000 early
      neonatal deaths could be prevented annually if all pregnant women used >90 IFA
      supplements and started at or before the 5th month of pregnancy. CONCLUSIONS: Any
      use of IFA supplements was significantly associated with reduced risk of early
      neonatal deaths in Nepal and Pakistan. The greatest mortality sparing effect of
      IFA on early neonatal deaths in both countries was with early initiation and use
      of a greater number of supplements.

PMID- 25398012
TI  - Comparative study of three flexiVent system configurations using mechanical test
      loads.
AB  - The sole commercial system currently employing the forced oscillation technique
      (FOT) in small laboratory animals (flexiVent; SCIREQ Inc., Canada) was recently
      redesigned along with its operating software. Yet, many users still work with the
      legacy version or a mixed configuration. This study aimed to compare result
      accuracy and precision between three flexiVent system configurations and to
      quantify the impact of configuration changes on measured parameters.
      Physiologically relevant resistance or elastance were measured at 2.5 Hz on the
      following three system configurations using characterized mechanical test loads:
      (i) legacy flexiVent-flexiVent v5.3.4 (Leg-fV5), (ii) legacy flexiVent-flexiWare
      v7.2.1 (Leg-fW7), and (iii) flexiVent FX-flexiWare v7.2.1 (FX-fW7). Results
      demonstrated measurements of high precision that were consistent between system
      configurations. There was no statistical difference between system configurations
      in terms of measuring a predicted resistance. Measurements of elastance, on the
      other hand, were configuration-sensitive with FX-fW7 generating values that were
      closer to theoretical ones than the other two configurations. The largest impact
      on measurement outcomes was associated with the most noteworthy configuration
      change (i.e., software and hardware replacement). This effect was however
      constrained, with variations in the order of 3-5%, approximately. In conclusion,
      the latest version of the sole commercial pre-clinical FOT system currently
      available generated results that were equivalent or better than those acquired
      with two other system configurations. Given that configuration changes were
      associated with subtle parameter differences, best practice would recommend
      consistency within a study and reporting the full details of the system used.

PMID- 25398014
TI  - High-transparency polymer nanocomposites enabled by polymer-graft modification of
      particle fillers.
AB  - The role of polymeric ligands on the optical transparency of polymer-matrix
      composites is analyzed by evaluating the effect of surface modification on the
      scattering cross-section of particle fillers in uniform particle dispersions. For
      the particular case of poly(styrene-r-acrylonitrile)-grafted silica particles
      embedded in poly(methyl methacrylate), it is shown that the tethering of
      polymeric chains with appropriate optical properties (such as to match the
      effective refractive index of the brush particle to the embedding matrix)
      facilitates the reduction of the particle scattering cross-section by several
      orders of magnitude as compared to pristine particle analogues. The conditions
      for minimizing the scattering cross-section of particle fillers by polymer-graft
      modification are established on the basis of effective medium as well as core
      shell Mie theory and validated against experimental data on uniform liquid and
      solid particle dispersions. Effective medium theory is demonstrated to provide
      robust estimates of the "optimum polymer-graft composition" to minimize the
      scattering cross-section of particle fillers even in the limit of large particle
      dimensions (comparable to the wavelength of light). The application of polymer
      graft modification to the design of large (500 nm diameter) silica particle
      composites with reduced scattering cross-section is demonstrated. 

PMID- 25398015
TI  - Diastereoselective synthesis of 2-arylmethylene-6-hydroxyspiro[4.5]deca-7-ones
      via FeCl3.6H2O-catalyzed spiroannulation/hydride transfer of 6-(5-arylpent-4-yn-1
      yl)-7-oxabicyclo[4.1.0]heptan-2-ols.
AB  - In the presence of a catalytic amount of FeCl3.6H2O, 6-(5-arylpent-4-yn-1-yl)-7
      oxabicyclo[4.1.0]heptan-2-ols underwent attack of the pendant acetylene at the
      iron-activated oxirane to give a vinylic carbocation. Hydride transfer from the
      carbinol carbon to the newly formed cation center furnished 2-arylmethylene-6
      hydroxyspiro[4.5]deca-7-ones in excellent stereoselectivity and good yields. 

PMID- 25398013
TI  - Differences in the activities of eight enzymes from ten soil fungi and their
      possible influences on the surface structure, functional groups, and element
      composition of soil colloids.
AB  - How soil fungi function in soil carbon and nutrient cycling is not well
      understood by using fungal enzymatic differences and their interactions with soil
      colloids. Eight extracellular enzymes, EEAs (chitinase, carboxymethyl cellulase,
      beta-glucosidase, protease, acid phosphatase, polyphenol oxidase, laccase, and
      guaiacol oxidase) secreted by ten fungi were compared, and then the fungi that
      showed low and high enzymatic activity were co-cultured with soil colloids for
      the purpose of finding fungi-soil interactions. Some fungi (Gomphidius rutilus,
      Russula integra, Pholiota adiposa, and Geastrum mammosum) secreted 3-4 enzymes
      with weak activities, while others (Cyathus striatus, Suillus granulate, Phallus
      impudicus, Collybia dryophila, Agaricus sylvicola, and Lactarius deliciosus)
      could secret over 5 enzymes with high activities. The differences in these fungi
      contributed to the alterations of functional groups (stretching bands of O-H, N
      H, C-H, C = O, COO- decreased by 11-60%, while P = O, C-O stretching, O-H bending
      and Si-O-Si stretching increased 9-22%), surface appearance (disappearance of
      adhesive organic materials), and elemental compositions (11-49% decreases in C1s)
      in soil colloids. Moreover, more evident changes were generally in high enzymatic
      fungi (C. striatus) compared with low enzymatic fungi (G. rutilus). Our findings
      indicate that inter-fungi differences in EEA types and activities might be
      responsible for physical and chemical changes in soil colloids (the most active
      component of soil matrix), highlighting the important roles of soil fungi in soil
      nutrient cycling and functional maintenance. 

PMID- 25398016
TI  - Boolean modelling reveals new regulatory connections between transcription
      factors orchestrating the development of the ventral spinal cord.
AB  - We have assembled a network of cell-fate determining transcription factors that
      play a key role in the specification of the ventral neuronal subtypes of the
      spinal cord on the basis of published transcriptional interactions. Asynchronous
      Boolean modelling of the network was used to compare simulation results with
      reported experimental observations. Such comparison highlighted the need to
      include additional regulatory connections in order to obtain the fixed point
      attractors of the model associated with the five known progenitor cell types
      located in the ventral spinal cord. The revised gene regulatory network
      reproduced previously observed cell state switches between progenitor cells
      observed in knock-out animal models or in experiments where the transcription
      factors were overexpressed. Furthermore the network predicted the inhibition of
      Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide
      evidence for the existence of an as yet undescribed inhibitory connection which
      could potentially have significance beyond the ventral spinal cord. The work
      presented in this paper demonstrates the strength of Boolean modelling for
      identifying gene regulatory networks. 

PMID- 25398018
TI  - Diagnostic value of total plasma lysophosphatidic acid in ovarian cancer: a meta
      analysis.
AB  - OBJECTIVE: This study aimed to assess the diagnostic value of lysophosphatidic
      acid (LPA) in ovarian cancer. METHODS: A systematic review of related studies was
      performed; sensitivity, specificity, and other measures about the accuracy of
      serum LPA in the diagnosis of ovarian cancer were pooled using random-effects
      models. Summary receiver operating characteristic curve analysis was used to
      summarize the overall test performance. RESULTS: Six studies involving 363
      patients with ovarian cancer and 273 healthy control women met the inclusion
      criteria. The summary estimates for LPA in diagnosing ovarian cancer in the
      included studies were as follows: sensitivity, 0.94 [95% confidence interval
      (CI), 0.91-0.96]; specificity, 0.88 (95% CI, 0.83-0.91); and diagnostic odds
      ratio, 141.59 (95% CI, 52.1-384.63). The area under the curve and Q value for
      summary receiver operating characteristic curves were 0.97 and 0.92,
      respectively. CONCLUSIONS: The LPA assay showed high accuracy and sensitivity for
      the diagnosis of ovarian cancer. The present study was limited by the small
      number of available studies and sample size; therefore, additional studies with a
      better design and larger samples are needed to further assess the diagnostic
      accuracy of LPA.

PMID- 25398017
TI  - De novo chemoattractants form supramolecular hydrogels for immunomodulating
      neutrophils in vivo.
AB  - Most immunomodulatory materials (e.g., vaccine adjuvants such as alum) modulate
      adaptive immunity, and yet little effort has focused on developing materials to
      regulate innate immunity, which get mentioned only when inflammation affects the
      biocompatibility of biomaterials. Traditionally considered as short-lived
      effector cells from innate immunity primarily for the clearance of invading
      microorganisms without specificity, neutrophils exhibit a key role in launching
      and shaping the immune response. Here we show that the incorporation of unnatural
      amino acids into a well-known chemoattractant-N-formyl-l-methionyl-l-leucyl-l
      phenylalanine (fMLF)-offers a facile approach to create a de novo,
      multifunctional chemoattractant that self-assembles to form supramolecular
      nanofibrils and hydrogels. This de novo chemoattractant not only exhibits
      preserved cross-species chemoattractant activity to human and murine neutrophils,
      but also effectively resists proteolysis. Thus, its hydrogel, in vivo, releases
      the chemoattractant and attracts neutrophils to the desired location in a
      sustainable manner. As a novel and general approach to generate a new class of
      biomaterials for modulating innate immunity, this work offers a prolonged acute
      inflammation model for developing various new applications. 

PMID- 25398019
TI  - Coping with cancer: examining the supports available to women with gynecologic
      cancer at Saskatoon Cancer Center.
AB  - OBJECTIVE: When women are diagnosed and treated for gynecologic cancer, they must
      find ways to cope. Cancer is both a physically and emotionally challenging
      disease. This study aims to identify existing coping strategies in women
      diagnosed with gynecologic cancer throughout their cancer journey and to add to
      these supports to help women cope with their cancer. METHODS: Women with
      gynecologic cancer were interviewed individually according to focus group
      principles during scheduled clinic visits at Saskatoon Cancer Center to identify
      coping strategies following diagnosis and treatment of cancer. Interviews were
      used to inform researchers before preparing a survey about coping with cancer.
      During 8 weeks, women receiving care were surveyed. Questions explored diagnosis,
      therapy phase, feelings, attitudes, and support. RESULTS: Sixteen women were
      interviewed; questionnaires were distributed to 75 women with cervical (20.7%),
      uterine (22.2%), ovarian (60.3%), and vulvar cancer (1.6%). After diagnosis, the
      major support was family in 96.8%, and talking helped in 71.4%. All women found
      their gynecologic oncologist and nurse were easy to talk to/supportive. Only
      12.7% attended counseling, 17.5% attended workshops/patient education sessions,
      and 9.5% attended support groups. Reasons for not receiving supportive counseling
      were voiced. A small number of alternative therapies tried by 60.3% were deemed
      helpful in 97.4%. Parking at the cancer center was a stressor in 81%.
      Participants felt that the Saskatoon gynecologic cancer care team fulfilled their
      needs emotionally. Patients want information about workshops, support meetings,
      and other modalities to improve their quality of life during their cancer
      journey. CONCLUSION: Providing better quality and type of available supports may
      enhance the experience of women following diagnosis and during therapy for cancer
      and will help women to cope with cancer more effectively.

PMID- 25398020
TI  - Further insights into long-term trends in relative survival of vulvar cancer
      patients: a population-based study.
AB  - OBJECTIVE: The main objective of this article was to investigate the trends in
      relative survival in women diagnosed with invasive squamous cell vulvar cancer in
      the United States during the periods of 2004 to 2011 and to examine how these
      trends are associated with the stage of tumor at diagnosis. METHODS: We
      identified patients with primary invasive squamous cell vulvar cancer and
      recorded tumor stage in the Surveillance, Epidemiology, and End Results cancer
      registry database. Women younger than 40 years were excluded because of small
      number of patients in this age group. A flexible parametric model was used to
      estimate 1- and 2-year relative survival ratios and excess mortality rate.
      RESULTS: In total, 4647 women were identified with invasive squamous cell vulvar
      cancer and known tumor stage in the data set. One- and two-year relative survival
      ratios increased over time for women with tumors staged I to III but it decreased
      for women with tumor staged IV. The excess mortality rate was much larger for
      stage IV compared to the other stages. CONCLUSIONS: Trends in relative survival
      ratio for invasive vulvar cancer patients have opposite directions depending on
      the stage of tumor. The mechanism of such behavior is not fully known and yet to
      be examined in future studies. However, this finding highlights the importance of
      early detection of preinvasive and early stage disease.

PMID- 25398021
TI  - Transient blood flow in elastic coronary arteries with varying degrees of
      stenosis and dilatations: CFD modelling and parametric study.
AB  - In this paper, we have analysed pulsatile flow through partially occluded elastic
      arteries, to determine the haemodynamic parameters of wall shear stress (WSS),
      wall pressure gradient and pressure drops (DeltaP), contributing to enhanced flow
      resistance and myocardial ischaemic regions which impair cardiac contractility
      and cause increased work load on the heart. In summary, it can be observed that
      stenoses in an artery significantly influence the haemodynamic parameters of wall
      shear stress and pressure drop in contrast to dilatations case. This deduces that
      stenosis plays a more critical role in plaque growth and vulnerability in
      contrast to dilatation, and should be the key element in cardiovascular pathology
      and diagnosis. Through quantitative analysis of WSS and DeltaP, we have provided
      a clearer insight into the haemodynamics of atherosclerotic arteries.
      Determination of these parameters can be helpful to cardiologists, because it is
      directly implicated in the genesis and development of atherosclerosis. 

PMID- 25398023
TI  - Correction to: epidemiology of amyotrophic lateral sclerosis in Emilia Romagna
      Region (Italy): a population based study.

PMID- 25398022
TI  - N-3 PUFAs protect against aortic inflammation and oxidative stress in angiotensin
      II-infused apolipoprotein E-/- mice.
AB  - Abdominal aortic aneurysm is associated with infiltration of inflammatory cells
      into the aortic wall. The inflammatory response is also evident in animal models,
      such as apolipoprotein E-deficient (ApoE-/-) mice that have been infused with
      angiotensin II, prior to development of aortic aneurysm. Since omega-3
      polyunsaturated fatty acids (n-3 PUFAs) and their metabolites have anti
      inflammatory and pro-resolving activity, we hypothesised that dietary
      supplementation with n-3 PUFAs would protect against inflammatory processes in
      this mouse model. Twenty C57 and 20 ApoE-/- 3-4 week old male mice were
      supplemented with a low (0.14%, n = 10/group) or high (0.70%, n = 10/group) n-3
      PUFA diet for 8 weeks before 2-day infusion with 0.9% saline or angiotensin II
      (1000 ng/kg/min). Four ApoE-/- mice on the low n-3 PUFA diet and none of the ApoE
      /- mice on the high n-3 PUFA diet showed morphological evidence of abdominal
      aortic dissection. The plasma concentration of the n-3 PUFA metabolite, resolvin
      D1 was higher in angiotensin II-infused ApoE-/- mice fed the high, compared to
      the low n-3 PUFA diet. The number of neutrophils and macrophages infiltrating the
      abdominal aorta was elevated in ApoE-/- mice on the low n-3 PUFA diet, and this
      was significantly attenuated in mice that were fed the high n-3 PUFA diet. Most
      neutrophils and macrophages were associated with dissected aortas.
      Immunoreactivity of the catalytic subunit of nicotinamide-adenine dinucleotide
      phosphate (NADPH) oxidase, Nox2, and superoxide were elevated in ApoE-/- mice
      that were fed the low n-3 PUFA diet, and this was also significantly attenuated
      in mice that were fed the high n-3 PUFA diet. Together, the findings indicate
      that supplementation of ApoE-/- mice with a diet high in n-3 PUFA content
      protected the mice against pro-inflammatory and oxidative stress responses
      following short-term infusion with angiotensin II. 

PMID- 25398024
TI  - Plasma jet printing of electronic materials on flexible and nonconformal objects.
AB  - We present a novel approach for the room-temperature fabrication of conductive
      traces and their subsequent site-selective dielectric encapsulation for use in
      flexible electronics. We have developed an aerosol-assisted atmospheric pressure
      plasma-based deposition process for efficiently depositing materials on flexible
      substrates. Silver nanowire conductive traces and silicon dioxide dielectric
      coatings for encapsulation were deposited using this approach as a demonstration.
      The paper substrate with silver nanowires exhibited a very low change in
      resistance upon 50 cycles of systematic deformation, exhibiting high mechanical
      flexibility. The applicability of this process to print conductive traces on
      nonconformal 3D objects was also demonstrated through deposition on a 3D-printed
      thermoplastic object, indicating the potential to combine plasma printing with 3D
      printing technology. The role of plasma here includes activation of the material
      present in the aerosol for deposition, increasing the deposition rate, and plasma
      polymerization in the case of inorganic coatings. The demonstration here
      establishes a low-cost, high-throughput, and facile process for printing
      electronic components on nonconventional platforms. 

PMID- 25398025
TI  - Identifying modulators of CXC receptors 3 and 4 with tailored selectivity using
      multi-target docking.
AB  - The G protein-coupled receptors of the C-X-C subfamily form a group among the
      chemokine receptors whose endogenous ligands are peptides with a common Cys-X-Cys
      motif. The CXC chemokine receptors 3 and 4 (CXCR3, CXCR4), which are investigated
      in this study, are linked to severe diseases such as cancer, multiple sclerosis,
      and HIV infections. Of particular interest, this receptor pair potentially forms
      a target for a polypharmacological drug treatment. Considering known ligands from
      public databases, such dual binders have not been identified yet. We therefore
      applied large-scale docking to the structure of CXCR4 and a homology model of
      CXCR3 with the goal to predict such dual binders, as well as compounds selective
      for either one of the receptors. Using signaling and biochemical assays, we
      showed that more than 50% of these predictions were correct in each category,
      yielding ligands with excellent binding efficiencies. These results highlight
      that docking is a suitable tool for the identification of ligands with tailored
      binding profiles to GPCRs, even when using homology models. More importantly, we
      present novel CXCR3-CXCR4 dual modulators that might pave the road to
      understanding the mechanisms of polypharmacological inhibition of these
      receptors.

PMID- 25398028
TI  - Dendrimeric template of Plasmodium falciparum histidine rich protein II repeat
      motifs bearing Asp->Asn mutation exhibits heme binding and beta-hematin
      formation.
AB  - Plasmodium falciparum (Pf) employs a crucial PfHRPII catalyzed reaction that
      converts toxic heme into hemozoin. Understanding heme polymerization mechanism is
      the first step for rational design of new drugs, targeting this pathway. Heme
      binding and hemozoin formation have been ascribed to PfHRPII aspartate
      carboxylate-heme metal ionic interactions. To investigate, if this ionic
      interaction is indeed pivotal, we examined the comparative heme binding and beta
      hematin forming abilities of a wild type dendrimeric peptide BNT1 {harboring the
      native sequence motif of PfHRPII (AHHAHHAADA)} versus a mutant dendrimeric
      peptide BNTM {in which ionic Aspartate residues have been replaced by the neutral
      Asparaginyl residues (AHHAHHAANA)}. UV and IR data reported here reveal that at
      pH 5, both BNT1 and BNTM exhibit comparable heme binding as well as beta-hematin
      forming abilities, thus questioning the role of PfHRPII aspartate carboxylate
      heme metal ionic interactions in heme binding and beta-hematin formation. Based
      on our data and information in the literature we suggest the possible role of
      weak dispersive interactions like N-H...pi and lone-pair...pi in heme binding and
      hemozoin formation. 

PMID- 25398027
TI  - Identification of functionally important residues of the rat P2X4 receptor by
      alanine scanning mutagenesis of the dorsal fin and left flipper domains.
AB  - Crystallization of the zebrafish P2X4 receptor in both open and closed states
      revealed conformational differences in the ectodomain structures, including the
      dorsal fin and left flipper domains. Here, we focused on the role of these
      domains in receptor activation, responsiveness to orthosteric ATP analogue
      agonists, and desensitization. Alanine scanning mutagenesis of the R203-L214
      (dorsal fin) and the D280-N293 (left flipper) sequences of the rat P2X4 receptor
      showed that ATP potency/efficacy was reduced in 15 out of 26 alanine mutants. The
      R203A, N204A, and N293A mutants were essentially non-functional, but receptor
      function was restored by ivermectin, an allosteric modulator. The I205A, T210A,
      L214A, P290A, G291A, and Y292A mutants exhibited significant changes in the
      responsiveness to orthosteric analog agonists 2-(methylthio)adenosine 5'
      triphosphate, adenosine 5'-(gamma-thio)triphosphate, 2'(3'-O-(4
      benzoylbenzoyl)adenosine 5'-triphosphate, and alpha,beta-methyleneadenosine 5'
      triphosphate. In contrast, the responsiveness of L206A, N208A, D280A, T281A,
      R282A, and H286A mutants to analog agonists was comparable to that of the wild
      type receptor. Among these mutants, D280A, T281A, R282A, H286A, G291A, and Y292A
      also exhibited increased time-constant of the desensitizing current response.
      These experiments, together with homology modeling, indicate that residues
      located in the upper part of the dorsal fin and left flipper domains, relative to
      distance from the channel pore, contribute to the organization of the ATP binding
      pocket and to the initiation of signal transmission towards residues in the lower
      part of both domains. The R203 and N204 residues, deeply buried in the protein,
      may integrate the output signal from these two domains towards the gate. In
      addition, the left flipper residues predominantly account for the control of
      transition of channels from an open to a desensitized state. 

PMID- 25398029
TI  - Encouraging careers in clinical research in spinal cord injury/dysfunction.

PMID- 25398026
TI  - Applications of hydrogen/deuterium exchange MS from 2012 to 2014.

PMID- 25398030
TI  - Subepidermal moisture surrounding pressure ulcers in persons with a spinal cord
      injury: a pilot study.
AB  - OBJECTIVE: Characterization of a non-invasive method of quantifying subepidermal
      moisture (SEM) surrounding stages III and IV pressure ulcers (PrUs) in spinal
      cord injury (SCI). DESIGN: Prospective, single-visit, single-rater, observational
      study, using repeated-measures analysis. Method Setting-inpatient units of one VA
      SCI Center. PARTICIPANTS: Convenience sample of 16 subjects with SCI with stage
      III or IV PrUs over sacrum or ischium. Interventions Measurement with the
      MoistureMeter-D, a hand-held device using 300 MHz electromagnetic waves. Outcome
      measures Dielectric constant, a dimensionless number which increases with the
      moisture content. Each subject had a PrU site and a control site. Measurements
      were made at each site, on intact skin, at four points spaced angularly around
      the site, in triplicate. Results (1) Short-term, single-rater relative error was
      2.5%. (2) Order effect: first readings were higher than second readings in 55 of
      64 measurement sets. Order effect was significant for control sites (P < 0.0001)
      but not for PrU sites. (3) Angular effect: SEM varied by angle at the PrU sites
      (P < 0.01); 12 o'clock position the highest and 6 o'clock the lowest. (4) Ability
      to differentiate PrUs from intact skin: SEM at PrU sites was greater by 9.0% than
      control sites (P < 0.05). (5) Site effect: SEM was higher at sacral locations
      than ischial at control sites by 20% (P < 0.005). CONCLUSIONS: SEM differentiates
      PrUs from intact skin. Future study designs must take into account order,
      angular, and site effects on this measure. This information will inform designers
      of future studies of SEM in healing of PrUs.

PMID- 25398031
TI  - PDE 2013, Paris, France: another exciting workshop for cyclic AMP, protein kinase
      A, and phosphodiesterases.

PMID- 25398032
TI  - Charge transport across insulating self-assembled monolayers: non-equilibrium
      approaches and modeling to relate current and molecular structure.
AB  - This paper examines charge transport by tunneling across a series of electrically
      insulating molecules with the structure HS(CH2)4CONH(CH2)2R) in the form of self
      assembled monolayers (SAMs), supported on silver. The molecules examined were
      studied experimentally by Yoon et al. (Angew. Chem. Int. Ed. 2012, 51, 4658
      4661), using junctions of the structure AgS(CH2)4CONH(CH2)2R//Ga2O3/EGaIn. The
      tail group R had approximately the same length for all molecules, but a range of
      different structures. Changing the R entity over the range of different
      structures (aliphatic to aromatic) does not influence the conductance
      significantly. To rationalize this surprising result, we investigate transport
      through these SAMs theoretically, using both full quantum methods and a generic,
      independent-electron tight-binding toy model. We find that the highest occupied
      molecular orbital, which is largely responsible for the transport in these
      molecules, is always strongly localized on the thiol group. The relative
      insensitivity of the current density to the structure of the R group is due to a
      combination of the couplings between the carbon chains and the transmission
      inside the tail. Changing from saturated to conjugated tail groups increases the
      latter but decreases the former. This work indicates that significant control
      over SAMs largely composed of nominally insulating groups may be possible when
      tail groups are used that are significantly larger than those used in the
      experiments of Yoon et al.1. 

PMID- 25398033
TI  - Point of view.

PMID- 25398034
TI  - Posterior reduction and temporary fixation for odontoid fracture: a salvage
      maneuver to anterior screw fixation.
AB  - STUDY DESIGN: A prospective study. OBJECTIVE: To evaluate the outcomes of
      posterior reduction and temporary fixation using the C1-C2 screw-rod system for
      odontoid fracture unsuitable for anterior screw fixation. SUMMARY OF BACKGROUND
      DATA: Anterior screw fixation has become the most widely used surgical procedure
      for the stabilization of odontoid fractures. However, if there is any
      contraindication for anterior fixation, posterior atlantoaxial fusion is
      preferred, eliminating the normal rotation of the atlantoaxial complex. METHODS:
      A consecutive series of 22 patients with odontoid fracture unsuitable for
      anterior screw fixation were involved in this study. Posterior reduction and
      fixation without fusion using the C1-C2 screw-rod system was performed. Once
      fracture healing was obtained, instrumentation was removed. The visual analogue
      scale of neck pain, neck stiffness, American Spinal Injury Association impairment
      scale, patient satisfaction, and neck disability index were recorded. The range
      of motion of C1-C2 in flexion-extension and rotation was calculated. RESULTS: The
      average age at internal fixation surgery was 40.2+/-11.3 years. The mean duration
      of follow-up was 41.8+/-26.8 months. There were no complications associated with
      instrumentation. All patients returned to their preoperative work. Fracture
      healing was observed in 21 patients and the instrumentation was removed. After
      removing the instrumentation, the visual analogue scale was reduced and neck
      stiffness were relieved (all P<0.01). Patient satisfaction and neck disability
      index had improved (all P<0.01). The range of motion of C1-C2 returned to 4.75
      degrees +/-1.62 degrees  and 25.70 degrees +/-5.51 degrees  in flexion-extension
      and in rotation, respectively. No osteoarthritis was observed at the C1-C2
      lateral mass joints. CONCLUSION: Posterior reduction and temporary fixation using
      the C1-C2 screw-rod system was an optimal salvage maneuver to anterior screw
      fixation for odontoid fracture. It could effectively avoid the motion loss of C1
      C2 caused by posterior atlantoaxial fusion. LEVEL OF EVIDENCE: 3.

PMID- 25398035
TI  - Greater operative volume is associated with lower complication rates in
      adolescent spinal deformity surgery.
AB  - STUDY DESIGN: Retrospective analysis of prospectively collected data from the
      2001 to 2010 Nationwide Inpatient Sample database. OBJECTIVE: To assess
      complication rates in adolescent spinal deformity by surgeon operative volume for
      procedures with a range of complexity. SUMMARY OF BACKGROUND DATA: Surgeons
      performing higher volumes of lumbar spinal fusion have been associated with
      improved surgical outcomes, according to studies using the Nationwide Inpatient
      Sample. This relationship has not been shown in adolescent spinal deformity
      surgery. METHODS: The Nationwide Inpatient Sample was queried for patients aged
      10 to 18 years with in-hospital stays including spinal arthrodesis for scoliosis
      (adolescent idiopathic, neuromuscular, and congenital scoliosis). The primary end
      point was hospital stay morbidity: database-defined surgical, mechanical, major
      medical, and neurological complications. Length of stay and hospital charges were
      also analyzed. Annual surgeon volumes were stratified into quartiles based on
      number of cases (Q1: 1, Q2: 2-7, Q3: 8-19, and Q4: 20-97). To account for
      variation in surgical invasiveness, an operative complexity index was used. One
      way analysis of variance was used to assess differences between quartiles for
      continuous measures and chi for categorical measures. RESULTS: A total of 6100
      spine fusion cases met inclusion criteria for adolescent scoliosis. All
      complications categories were less frequent for higher volume surgeons after a
      primary fusion for all diagnoses. This pattern held for increasing surgical
      invasiveness, such as fusing 9 or more levels and became more distinct for
      neurological complications when comparing surgeons performing combined anterior
      posterior procedures. Including all adolescent scoliosis fusions, higher surgical
      volume was associated with decreased length of stay and hospital charges.
      CONCLUSION: Perioperative complications after adolescent scoliosis fusion surgery
      are more frequent in lower volume settings. This may reflect a learning curve
      required for more complex cases as the trends are magnified in
      neuromuscular/congenital scoliosis cases or simply that higher volume surgeons
      are more adept at these fusions. The impact of volume on reduced length of stay
      and hospital charges has implications for future health care economics measures.
      LEVEL OF EVIDENCE: 2.

PMID- 25398036
TI  - Intraoperative skull-femoral traction in posterior spinal arthrodesis for
      adolescent idiopathic scoliosis: the impact on perioperative outcomes and health
      resource utilization.
AB  - STUDY DESIGN: Retrospective, single-center cohort study. OBJECTIVE: To study how
      the systematic use of intraoperative skull-femoral traction (IOSFT) in posterior
      arthrodesis for adolescent idiopathic scoliosis impacts perioperative outcomes
      and health resource utilization. SUMMARY OF BACKGROUND DATA: Large scoliosis
      curves have been associated with increased morbidity and utilization of health
      resources. When used with reliable neurophysiological monitoring, IOSFT has shown
      to be safe and to reduce curve magnitude intraoperatively. Thus, we hypothesized
      that the systematic use of IOSFT may contribute to reducing health resource
      utilization by reducing curve magnitudes intraoperatively. METHODS: Seventy-three
      consecutive patients with adolescent idiopathic scoliosis who underwent single
      stage posterior spinal arthrodesis from 2008 to 2012 at a tertiary children's
      hospital were identified. Forty-five patients were operated with IOSFT (traction
      group) and 28 patients were operated without IOSFT (nontraction group). Outcome
      measures included operative time, calculated blood loss, blood transfusion
      requirement, traction-related complications, and cost comparisons. RESULTS:
      Operative time was 375.6 minutes for the traction group (P=0.0001) and 447.6
      minutes for the nontraction group. Calculated blood loss was significantly less
      in the traction group (P=0.027). Thirty-three percent of patients in the traction
      group required blood transfusion compared with 64% of patients in the nontraction
      group (P=0.01, absolute risk reduction of 31%). There was no significant
      difference in curve magnitude correction (P=0.49). There were no significant
      complications with the use of traction. There was a significant reduction in cost
      per surgical procedure in the traction group (P=0.0003). CONCLUSION: The
      systematic use of IOSFT in posterior spinal arthrodesis for adolescent idiopathic
      scoliosis contributed to significant reductions in health resource utilization,
      with no added morbidity. Further research is warranted to investigate the
      generalizability of these findings. LEVEL OF EVIDENCE: 4.

PMID- 25398037
TI  - Success in esophageal perforation repair with open-wound management after
      revision cervical spine surgery: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To share our successful experience in
      treating 1 case of esophageal perforation after anterior revision cervical spine
      surgery with open-wound management. SUMMARY OF BACKGROUND DATA: Early diagnosis
      and surgical treatment is widely adopted in the management of esophageal
      complications after anterior cervical spine surgery, but the management of wound
      after surgical repair of esophageal perforation is rarely discussed. METHODS: One
      patient underwent revision anterior cervical spine surgery because of displaced
      hardware and poor alignment of cervical spine. Esophageal perforation was
      incurred intraoperatively and found on the first postoperative day. Repair
      surgery was carried out immediately afterward. During the surgery, esophageal
      perforation was closed with a suture, and reinforced with a sternocleidomastoid
      muscle flap. The wound was loosely closed with aspirating drainage. Two days
      after the surgery, the patient began to show signs of recurrent esophageal
      leakage and severe secondary wound infection. The wound was then reopened
      completely before a continuous irrigation and drainage system was positioned in
      place. RESULT: In 12 weeks, the esophageal perforation healed without
      complications or loosening of instrumentation. CONCLUSION: Open-wound management
      succeeded in this patient after surgical repair of esophageal perforation caused
      by revision anterior cervical spine surgery. LEVEL OF EVIDENCE: 4.

PMID- 25398038
TI  - An anatomic study to determine the optimal entry point, medial angles, and
      effective length for safe fixation using posterior C1 lateral mass screws.
AB  - STUDY DESIGN: Anatomic study of the C1 lateral mass using fine-cut computed
      tomographic scans and Mimics software. OBJECTIVE: To investigate the optimal
      entry point, medial angles, and effective length for safe fixation using
      posterior C1 lateral mass screws. SUMMARY OF BACKGROUND DATA: Placing posterior
      C1 lateral mass screws is technically demanding, and a misplaced screw can result
      in injury to the vertebral artery, spinal cord, or internal carotid artery.
      Although various insertion angles have been proposed for posterior C1 lateral
      mass screw, no clear consensus has been reached on the ideal medial angle of the
      C1 lateral mass. METHODS: The C1 lateral masses were evaluated using computed
      tomographic scans and Mimics software in 70 patients. The effective width and
      effective screw length of posterior C1 lateral mass screws were measured at
      different medial angulations relative to the midline sagittal plane. The height
      (H) for screw entry point on the posterior surface of C1 lateral mass and the
      distance (D) between screw entry point and the intersection of the midline
      sagittal plane and the posterior arch of the atlas were also measured. RESULTS:
      The mean height (H) for screw entry on the posterior surface of the lateral mass
      was 4.25 mm, the mean distance (D) between screw entry point and the intersection
      of the midsagittal plane and the posterior arch of the atlas was 27.62 mm. The
      optimal medial angle was 20.86 degrees  with a corresponding effective width of
      10.56 mm and effective screw length of 21.87 mm. CONCLUSION: This study helps to
      define the specific anatomy related to C1 posterior lateral mass screw placement
      in an effort to facilitate instrumentation. However, variation is seen in lateral
      mass anatomy, and this study must be combined with customized surgical planning
      that includes advanced imaging for safe and effective instrumentation. LEVEL OF
      EVIDENCE: 1.

PMID- 25398039
TI  - Direct repair surgery with screw fixation for young patients with lumbar
      spondylolysis: patient-reported outcomes and fusion rate in a prospective
      interventional study.
AB  - STUDY DESIGN: Prospective interventional study. OBJECTIVES: To thoroughly
      investigate the therapeutic outcomes of direct repair (DR) for young patients
      with lumbar spondylolysis. SUMMARY OF BACKGROUND DATA: DR surgery with screw
      fixation for a pars defect of lumbar spondylolysis is considered a notable
      surgical option. However, prior studies do not provide clear information on the
      significance of DR and its outcomes in young patients with lumbar spondylolysis
      because most previous studies in this area were conducted with spondylolysis
      patients of all ages and with low-quality study designs that were retrospective
      in design and had a small sample size and short follow-up time. METHODS: A total
      of 47 young patients with lumbar spine spondylolysis who were surgically treated
      with DR surgery and followed up for 1 year after surgery were enrolled in this
      study. The primary outcome was degree of pain assessed by visual analogue scale,
      which separately recorded pain intensity and pain frequency. Secondary outcomes
      included (1) patient satisfaction, (2) clinical outcomes based on Oswestry
      Disability Index score and a 12-item short form health survey, (3) fusion rate of
      pars defect based on computed tomographic scans, and (4) surgery-related
      complications. RESULTS: The degree of lower back pain (intensity and frequency)
      significantly improved at final follow-up compared with preoperative level.
      However, 6 patients (13%) had no significant improvement, and pain frequency
      tended to worsen 6 months after the operation. Only 25 patients (53%) were
      satisfied with DR surgery. One-year postoperative clinical outcomes (Oswestry
      Disability Index and 12-item short form health survey) significantly improved
      compared with preoperative levels, but the 2 scores also tended to decrease after
      6 months. The union rate of the pars defect was 55% (26/47). There was no
      significant difference in clinical outcomes between fusion group and nonunion
      group of the pars defect at the final follow-up. Two patients (4%) experienced
      surgery-related complications. CONCLUSION: The authors suggest that DR surgery in
      young patients with lumbar spondylolysis may produce unsatisfactory outcomes at 1
      year after surgery. LEVEL OF EVIDENCE: 2.

PMID- 25398040
TI  - Tree-ring stable isotopes reveal twentieth-century increases in water-use
      efficiency of Fagus sylvatica and Nothofagus spp. in Italian and Chilean
      mountains.
AB  - Changes in intrinsic water use efficiency (iWUE) were investigated in Fagus
      sylvatica and Nothofagus spp. over the last century. We combined
      dendrochronological methods with dual-isotope analysis to investigate whether
      atmospheric changes enhanced iWUE of Fagus and Nothofagus and tree growth (basal
      area increment, BAI) along latitudinal gradients in Italy and Chile. Post
      maturation phases of the trees presented different patterns in delta13C,
      Delta13C, delta18O, Ci (internal CO2 concentration), iWUE, and BAI. A continuous
      enhancement in isotope-derived iWUE was observed throughout the twentieth
      century, which was common to all sites and related to changes in Ca (ambient CO2
      concentration) and secondarily to increases in temperature. In contrast to other
      studies, we observed a general increasing trend of BAI, with the exception of F.
      sylvatica in Aspromonte. Both iWUE and BAI were uncoupled with the estimated
      drought index, which is in agreement with the absence of enduring decline in tree
      growth. In general, delta13C and delta18O showed a weak relationship, suggesting
      the major influence of photosynthetic rate on Ci and delta13C, and the minor
      contribution of the regulation of stomatal conductance to iWUE. The substantial
      warming observed during the twentieth century did not result in a clear pattern
      of increased drought stress along these latitudinal transects, because of the
      variability in temporal trends of precipitation and in specific responses of
      populations. 

PMID- 25398042
TI  - Experimental and theoretical kinetics for the H2O+ + H2/D2 -> H3O+/H2DO+ + H/D
      reactions: observation of the rotational effect in the temperature dependence.
AB  - Thermal rate coefficients for the title reactions computed using a quasi
      classical trajectory method on an accurate global potential energy surface fitted
      to ~81,000 high-level ab initio points are compared with experimental values
      measured between 100 and 600 K using a variable temperature selected ion flow
      tube instrument. Excellent agreement is found across the entire temperature
      range, showing a subtle, but unusual temperature dependence of the rate
      coefficients. For both reactions the temperature dependence has a maximum around
      350 K, which is a result of H2O(+) rotations increasing the reactivity, while
      kinetic energy is decreasing the reactivity. A strong isotope effect is found,
      although the calculations slightly overestimate the kinetic isotope effect. The
      good experiment-theory agreement not only validates the accuracy of the potential
      energy surface but also provides more accurate kinetic data over a large
      temperature range. 

PMID- 25398041
TI  - Head movements in patients with vestibular lesion: a novel approach to functional
      assessment in daily life setting.
AB  - OBJECTIVES: (1) To determine if head movements in patients with vestibular
      deficiency differ from those in normal subjects during daily life activities. (2)
      To assess if these differences can be correlated with patients' perception of
      dizziness-induced handicap. STUDY DESIGN: Prospective matched-pairs study
      SETTING: Tertiary referral center PATIENTS: Thirty-one vestibular schwannoma
      patients with documented postoperative unilateral vestibular loss and their age-,
      gender-, and physical activity level-matched controls with symmetric vestibulo
      ocular reflexes. INTERVENTIONS: Head movements during 10 tasks from daily life
      were recorded using body-worn movement sensors. MAIN OUTCOME MEASURES: The time
      to complete the task, the average head velocity and acceleration during each
      task, and the number of head turns performed were compared between cases and
      controls. These measures were then correlated with the self-reported Dizziness
      Handicap Inventory (DHI) scores of the patients. RESULTS: Patients with a
      unilateral vestibular deficit took significantly longer to perform most daily
      life activities compared to controls. Their head movements, however, were not
      always slower. They adopted a different movement strategy, in certain instances
      less efficient and more disorganized. Dimensions of movement are not all affected
      equally after a unilateral vestibular loss with evidence of clear clustering of
      the differences within dimensions across tasks. There was no correlation between
      the DHI and patients' performance in those tasks. CONCLUSION: Vestibular loss,
      even when compensated, affects patients' movements, which can be measured in an
      ambulatory setting of daily life activities. The differences in movements
      associated with vestibular loss do not correlate with the degree of self-reported
      handicap.

PMID- 25398043
TI  - Effect of intermolecular force on the static/dynamic behaviour of M/NEM devices.
AB  - Advances made in the fabrication of micro/nano-electromechanical (M/NEM) devices
      over the last ten years necessitate the understanding of the attractive force
      that arises from quantum fluctuations (generally referred to as Casimir effects)
      [Casimir H B G 1948 Proc. K. Ned. Akad. Wet. 51 793]. The fundamental mechanisms
      underlying quantum fluctuations have been actively investigated through various
      theoretical and experimental approaches. However, the effect of the force on
      M/NEM devices has not been fully understood yet, especially in the transition
      region involving gaps ranging from 10 nm to 1 MUm, due to the complexity of the
      force. Here, we numerically calculate the Casimir effects in M/NEM devices by
      using the Lifshitz formula, the general expression for the Casimir effects
      [Lifshitz E 1956 Sov. Phys. JETP 2 73]. Since the Casimir effects are highly
      dependent on the permittivity of the materials, the Kramer-Kronig relation
      [Landau L D, Lifshitz E M and Pitaevskii L P 1984 Electrodynamics of Continuous
      Media (New York: Pergamon Press)] and the optical data for metals and dielectrics
      are used in order to obtain the permittivity. Several simplified models for the
      permittivity of the materials, such as the Drude and Lorentz models [Jackson J D
      1975 Classical Electrodynamics (New York: Wiley)], are also used to extrapolate
      the optical data. Important characteristic values of M/NEM devices, such as the
      pull-in voltage, pull-in gap, detachment length, etc, are calculated for devices
      operating in the transition region. Our results show that accurate predictions
      for the pull-in behaviour are possible when the Lifshitz formula is used instead
      of the idealized expressions for Casimir effects. We expand this study into the
      dynamics of M/NEM devices, so that the time and frequency response of M/NEM
      devices with Casimir effects can be explored. 

PMID- 25398044
TI  - Recent evolutions in pediatric and congenital echocardiography.
AB  - PURPOSE OF REVIEW: Echocardiography is the first-line diagnostic technique in
      patients with congenital heart disease. Recent developments include further
      standardization of pediatric and congenital echocardiography with general
      specific and lesion-specific guidelines. New research focuses on clinical
      validation of echocardiographic quantitative techniques for assessing right
      ventricular and single ventricular function. RECENT FINDINGS: Recent guidelines
      include standardization of pediatric echocardiographic measurements and
      description of utilization of imaging techniques in patients diagnosed with
      tetralogy of Fallot. Description of resource utilization and organizational
      standards, including systems for quality assurance, are important tools for
      improving the diagnostic quality of pediatric echocardiographic laboratories. We
      highlight interesting new research on the echocardiographic assessment of right
      ventricular function in patients after tetralogy of Fallot repair, patients with
      single-ventricle physiology and pediatric cardiomyopathies. SUMMARY: Pediatric
      and congenital echocardiography is evolving as an important specific area within
      echocardiography. It is developing its own standards and quality control, and
      research in this field focuses on development of more quantitative methods for
      assessing ventricular function.

PMID- 25398045
TI  - Bond activation and catalysis by ruthenium pincer complexes.

PMID- 25398048
TI  - Duration perception of emotional stimuli: Using evaluative conditioning to avoid
      sensory confounds.
AB  - It has been found that emotional pictures are estimated to last longer than
      neutral ones. However, emotional and neutral stimuli often differ in their
      physical characteristics, too. Since this might also affect time perception, we
      present a method disentangling a possible confounding regarding the processing of
      physically different stimulus material. In the evaluative condition paradigm,
      participants, at first, learnt the association of neutral images with a certain
      Landolt ring and of emotional images with another Landolt ring with a different
      gap position. The conditioned Landolt rings were subsequently used in a temporal
      bisection task. In two experiments, the results revealed a temporal
      overestimation of Landolt rings conditioned with emotional pictures compared to
      neutral pictures showing that the temporal overestimation of emotional stimuli
      cannot be attributed to perceptual differences between neutral and emotional
      stimuli. The method provides the potential for investigating emotional effects on
      various perceptual processes. 

PMID- 25398046
TI  - Genetic characterization of goutanap virus, a novel virus related to negeviruses,
      cileviruses and higreviruses.
AB  - Pools of mosquitoes collected in Cote d'Ivoire and Mexico were tested for
      cytopathic effects on the mosquito cell line C6/36. Seven pools induced strong
      cytopathic effects after one to five days post infection and were further
      investigated by deep sequencing. The genomes of six virus isolates from Cote
      d'Ivoire showed pairwise nucleotide identities of ~99% among each other and of
      56%-60% to Dezidougou virus and Wallerfield virus, two insect-specific viruses
      belonging to the proposed new taxon Negevirus. The novel virus was tentatively
      named Goutanap virus. The isolate derived from the Mexican mosquitoes showed 95%
      pairwise identity to Piura virus and was suggested to be a strain of Piura virus,
      named C6.7-MX-2008. Phylogenetic inferences based on a concatenated alignment of
      the methyltransferase, helicase, and RNA-dependent RNA polymerase domains showed
      that the new taxon Negevirus formed two monophyletic clades, named Nelorpivirus
      and Sandewavirus after the viruses grouping in these clades. Branch lengths
      separating these clades were equivalent to those of the related genera Cilevirus,
      Higrevirus and Blunervirus, as well as to those within the family Virgaviridae.
      Genetic distances and phylogenetic analyses suggest that Nelorpivirus and
      Sandewavirus might form taxonomic groups on genus level that may define alone or
      together with Cilevirus, Higrevirus and Blunervirus a viral family.

PMID- 25398047
TI  - Anti-glycoprotein g antibodies of herpes simplex virus 2 contribute to complete
      protection after vaccination in mice and induce antibody-dependent cellular
      cytotoxicity and complement-mediated cytolysis.
AB  - We investigated the role of antibodies against the mature portion of glycoprotein
      G (mgG-2) of herpes simplex virus 2 (HSV-2) in protective immunity after
      vaccination. Mice were immunized intramuscularly with mgG-2 and
      oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All
      C57BL/6 mice survived and presented no genital or systemic disease. High levels
      of immunoglobulin G subclass 1 (IgG1) and IgG2 antibodies were detected and re
      stimulated splenic CD4+ T cells proliferated and produced IFN-gamma. None of the
      sera from immunized mice exhibited neutralization, while all sera exerted
      antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis
      (ACMC) activity. Passive transfer of anti-mgG-2 monoclonal antibodies, or immune
      serum, to naive C57BL/6 mice did not limit disease progression. Immunized B-cell
      KO mice presented lower survival rate and higher vaginal viral titers, as
      compared with vaccinated B-cell KO mice after passive transfer of immune serum
      and vaccinated C57BL/6 mice. Sera from mice that were vaccinated subcutaneously
      and intranasally with mgG-2 presented significantly lower titers of IgG
      antibodies and lower ADCC and ACMC activity. We conclude that anti-mgG-2
      antibodies were of importance to limit genital HSV-2 infection. ADCC and ACMC
      activity are potentially important mechanisms in protective immunity, and could
      tentatively be evaluated in future animal vaccine studies and in clinical trials.

PMID- 25398049
TI  - Facile base-mediated redox transformation: an efficient strategy for the
      synthesis of alpha-acyloxyphosphoryl compounds.
AB  - An efficient one-pot synthesis of alpha-acyloxyphosphoryl compounds from
      aldehydes and hydrogen phosphoryl compounds has been developed using a facile
      base-mediated redox strategy. This redox transformation is applicable to
      synthesize a wide range of valuable alpha-acyloxyphosphoryl compounds with high
      atom- and step-economic efficiency. 

PMID- 25398050
TI  - Metabolic mysteries of the inflammatory response: T cell polarization and
      plasticity.
AB  - While simultaneously maintaining homeostasis and reducing further harm to the
      host, the immune system is equipped to eliminate both tumors and pathogenic
      microorganisms. Bifurcated into cell-mediated and humoral immunity, the adaptive
      immune system requires a series of complex and coordinated signals to drive the
      proliferation and differentiation of appropriate subsets. These include signals
      that modulate cellular metabolism. When first published in the 1920s, "the
      Warburg effect" was used to describe a phenomenon in which most cancer cells
      relied on aerobic glycolysis to meet their biosynthetic demands. Despite the
      early observations of Warburg and his colleagues, targeting cancer cell
      metabolism for therapeutic purposes still remains theoretical. Notably, many T
      cells exhibit the same Warburg metabolism as cancer cells and the therapeutic
      benefit of targeting their metabolic pathways has since been reexamined. Emerging
      evidence suggests that specific metabolic alterations associated with T cells may
      be ancillary to their subset differentiation and influential in their
      inflammatory response. Thus, T cell lymphocyte activation leads to skewing in
      metabolic plasticity, and issue that will be the subject of this review. 

PMID- 25398051
TI  - Effect of acidic properties of mesoporous zeolites supporting pt nanoparticles on
      hydrogenative conversion of methylcyclopentane.
AB  - The effect of acidic properties of mesoporous zeolites on the control of product
      selectivity during the hydrogenative isomerization of methylcyclopentane has been
      investigated. A series of mesoporous zeolites with controlled acidic properties
      were prepared by postdealumination process with hydrochloric acid under
      hydrothermal conditions, and the resultant zeolites used for supporting colloidal
      Pt nanoparticles (NPs) with a mean size of 2.5 nm (+/- 0.6 nm). As compared to
      the pure Pt NPs supported on catalytically inert mesoporous silica (MCF-17) as
      the reference catalyst that can produce isomers most selectively (~80%), the Pt
      NPs supported on mesoporous zeolites produced C6-cyclic hydrocarbons (i.e.,
      cyclohexane and benzene) most dominantly. The type and strength of the Bronsted
      (B) and Lewis (L) acid sites of those zeolites with a controlled Al amount are
      analyzed by using FT-IR after the adsorption of pyridine and NH3 temperature
      programmed desorption measurements, and they are correlated with the selectivity
      change between cyclohexane and benzene. From this investigation, we found a
      linear relationship between the number of Bronsted acid sites and the formation
      rate for cyclohexane. In addition, we revealed that more Lewis acidic zeolite
      having relatively smaller B/L ratio is effective for the cyclohexane formation,
      whereas more Bronsted acidic zeolite having relatively larger B/L ratio is
      effective for the benzene formation.

PMID- 25398052
TI  - The ciliopathy gene Rpgrip1l is essential for hair follicle development.
AB  - The primary cilium is essential for skin morphogenesis through regulating the
      Notch, Wnt, and hedgehog signaling pathways. Prior studies on the functions of
      primary cilia in the skin were based on the investigations of genes that are
      essential for cilium formation. However, none of these ciliogenic genes has been
      linked to ciliopathy, a group of disorders caused by abnormal formation or
      function of cilia. To determine whether there is a genetic and molecular link
      between ciliopathies and skin morphogenesis, we investigated the role of
      RPGRIP1L, a gene mutated in Joubert (JBTS) and Meckel (MKS) syndromes, two severe
      forms of ciliopathy, in the context of skin development. We found that RPGRIP1L
      is essential for hair follicle morphogenesis. Specifically, disrupting the
      Rpgrip1l gene in mice resulted in reduced proliferation and differentiation of
      follicular keratinocytes, leading to hair follicle developmental defects. These
      defects were associated with significantly decreased primary cilium formation and
      attenuated hedgehog signaling. In contrast, we found that hair follicle induction
      and polarization and the development of interfollicular epidermis were
      unaffected. This study indicates that RPGRIP1L, a ciliopathy gene, is essential
      for hair follicle morphogenesis likely through regulating primary cilia formation
      and the hedgehog signaling pathway.

PMID- 25398053
TI  - Dominant De Novo Mutations in GJA1 Cause Erythrokeratodermia Variabilis et
      Progressiva, without Features of Oculodentodigital Dysplasia.
AB  - Genetic investigation of inherited skin disorders has informed the understanding
      of skin self-renewal, differentiation, and barrier function. Erythrokeratodermia
      variabilis et progressiva (EKVP) is a rare, inherited skin disease that is
      characterized by transient figurate patches of erythema, localized or generalized
      scaling, and frequent palmoplantar keratoderma. By using exome sequencing, we
      show that de novo missense mutations in GJA1 (gap junction protein alpha 1) cause
      EKVP. The severe, progressive skin disease in EKVP subjects with GJA1 mutations
      is distinct from limited cutaneous findings rarely found in the systemic disorder
      oculodentodigital dysplasia, also caused by dominant GJA1 mutations. GJA1 encodes
      connexin 43 (Cx43), the most widely expressed gap junction protein. We show that
      the GJA1 mutations in EKVP subjects lead to disruption of Cx43 membrane
      localization and aggregation within the Golgi. These findings reveal a critical
      role for Cx43 in epidermal homeostasis, and they provide evidence of organ
      specific pathobiology resulting from different mutations within GJA1. 

PMID- 25398055
TI  - Determining surface properties with bimodal and multimodal AFM.
AB  - Conventional dynamic atomic force microscopy (AFM) can be extended to bimodal and
      multimodal AFM in which the cantilever is simultaneously excited at two or more
      resonance frequencies. Such excitation schemes result in one additional amplitude
      and phase images for each driven resonance, and potentially convey more
      information about the surface under investigation. Here we present a theoretical
      basis for using this information to approximate the parameters of a tip-surface
      interaction model. The theory is verified by simulations with added noise
      corresponding to room-temperature measurements. 

PMID- 25398054
TI  - Characterization of quiescent epithelial cells in mouse meibomian glands and hair
      follicle/sebaceous glands by immunofluorescence tomography.

PMID- 25398056
TI  - Differential effects of the Toll-like receptor 2 agonists, PGN and Pam3CSK4 on
      anti-IgE induced human mast cell activation.
AB  - Mast cells are pivotal in the pathogenesis of allergy and inflammation. In
      addition to the classical IgE-dependent mechanism involving crosslinking of the
      high-affinity receptor for IgE (FcepsilonRI), mast cells are also activated by
      Toll-like receptors (TLRs) which are at the center of innate immunity. In this
      study, we demonstrated that the response of LAD2 cells (a human mast cell line)
      to anti-IgE was altered in the presence of the TLR2 agonists peptidoglycan (PGN)
      and tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3CSK4). Pretreatment of PGN and
      Pam3CSK4 inhibited anti-IgE induced calcium mobilization and degranulation
      without down-regulation of FcepsilonRI expression. Pam3CSK4 but not PGN acted in
      synergy with anti-IgE for IL-8 release when the TLR2 agonist was added
      simultaneously with anti-IgE. Studies with inhibitors of key enzymes implicated
      in mast cell signaling revealed that the synergistic release of IL-8 induced by
      Pam3CSK4 and anti-IgE involved ERK and calcineurin signaling cascades. The
      differential modulations of anti-IgE induced mast cell activation by PGN and
      Pam3CSK4 suggest that dimerization of TLR2 with TLR1 or TLR6 produced different
      modulating actions on FcepsilonRI mediated human mast cell activation. 

PMID- 25398057
TI  - What women think: cancer causal attributions in a diverse sample of women.
AB  - Women hold diverse beliefs about cancer etiology, potentially affecting their use
      of cancer preventive behaviors. Research has primarily focused on cancer causal
      attributions survivors and participants from non-diverse backgrounds hold. Less
      is known about attributions held by women with and without a family history of
      cancer from a diverse community sample. Participants reported factors they
      believed cause cancer. Open-ended responses were coded and relations between the
      top causal attributions and key factors were explored. Findings suggest certain
      socio-cultural factors play a role in the causal attributions women make about
      cancer, which can, in turn, inform cancer awareness and prevention messages. 

PMID- 25398058
TI  - Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella
      pneumoniae bacteremia in febrile neutropenic children.
AB  - This retrospective study was conducted to evaluate clinical outcomes of
      bacteremia caused by extended-spectrum beta-lactamase (ESBL)-producing
      Escherichia coli and Klebsiella pneumoniae and their antibiotic susceptibilities
      in febrile neutropenic children. Clinical characteristics, prognosis, and
      antibiotic susceptibilities were reviewed and compared between febrile
      neutropenic children with bacteremia caused by ESBL-producing and non-ESBL
      producing E. coli and K. pneumoniae. A total of 61 episodes of E. coli and K.
      pneumoniae bacteremia, including 21 episodes (34.4%) due to ESBL-producing
      strains, were diagnosed. There was no significant factor associated with
      bacteremia by ESBL-producing strains. Empirical antibiotics were appropriate in
      85.7% of the ESBL group and 95.0% of the non-ESBL group. In the entire study
      population, seven deaths (11.5%), including three deaths (4.9%) due to E. coli
      and K. pneumoniae bacteremia, occurred. The complication and mortality rates were
      not significantly different between the two groups. Antibiotic susceptibility
      rates were significantly lower in the ESBL group than in the non-ESBL group in
      most antibiotics. Although 52.4% and 66.7% of the ESBL-producing isolates were
      susceptible to piperacillin/tazobactam and cefepime, respectively, 96.7% of all
      the isolates and 90.5% of the ESBL-producing isolates were susceptible to
      piperacillin/tazobactam or cefepime in combination with aminoglycoside. In
      conclusion, the ESBL group did not show a significantly unfavorable outcome, and
      empirical therapy with piperacillin/tazobactam or cefepime in combination with
      aminoglycoside might be more useful for febrile neutropenic children, instead of
      beta-lactam monotherapy in institutions with high prevalence of ESBL-producing E.
      coli and K. pneumoniae. 

PMID- 25398061
TI  - The lymphoid variant of hypereosinophilic syndrome: study of 21 patients with CD3
      CD4+ aberrant T-cell phenotype.
AB  - The CD3-CD4+ aberrant T-cell phenotype is the most described in the lymphoid
      variant of hypereosinophilic syndrome (L-HES), a rare form of HES. Only a few
      cases have been reported, and data for these patients are scarce. To describe
      characteristics and outcome of CD3-CD4+ L-HES patients, we conducted a national
      multicentric retrospective study in the French Eosinophil Network. All patients
      who met the recent criteria of hypereosinophilia (HE) or HES and who had a
      persistent CD3-CD4+ T-cell subset on blood T-cell phenotyping were included.
      Clinical and laboratory data were retrospectively collected by chart review. CD3
      CD4+ L-HES was diagnosed in 21 patients (13 females, median age 42 years [range,
      5-75 yr]). Half (48%) had a history of atopic manifestations. Clinical
      manifestations were dermatologic (81%), superficial adenopathy (62%),
      rheumatologic (29%), gastrointestinal (24%), pulmonary (19%), neurologic (10%),
      and cardiovascular (5%). The median absolute CD3-CD4+ T-cell count was 0.35 G/L
      (range, 0.01-28.3), with a clonal TCRgammadelta rearrangement in 76% of patients.
      The mean follow-up duration after HES diagnosis was 6.9 +/- 5.1 years. All
      patients treated with oral corticosteroids (CS) (n = 18) obtained remission, but
      16 required CS-sparing treatments. One patient had a T-cell lymphoma 8 years
      after diagnosis, and 3 deaths occurred during follow-up.In conclusion, clinical
      manifestations related to CD3-CD4+ T cell-associated L-HES are not limited to
      skin, and can involve all tissue or organs affected in other types of HE.
      Contrary to FIP1L1-PDGFRA chronic eosinophilic leukemia patients, CS are always
      effective in these patients, but CS-sparing treatments are frequently needed. The
      occurrence of T-cell lymphoma, although rare in our cohort, remains a major
      concern during follow-up.

PMID- 25398062
TI  - Hepatosplenic cat scratch disease in immunocompetent adults: report of 3 cases
      and review of the literature.
AB  - Cat-scratch disease (CSD) is the most frequent presentation of Bartonella
      henselae infection. It has a worldwide distribution and is associated with a
      previous history of scratch or bite from a cat or dog. CSD affects children and
      teenagers more often (80%) than adults, and it usually has a self-limiting
      clinical course. Atypical clinical course or systemic symptoms are described in
      5%-20% of patients. Among them, hepatosplenic (HS) forms (abscess) have been
      described. The majority of published cases have affected children or
      immunosuppressed patients. Few cases of HS forms of CSD in immunocompetent adult
      hosts have been reported, and data about the management of this condition are
      scarce. Herein, we present 3 new cases of HS forms of CSD in immunocompetent
      adults and review 33 other cases retrieved from the literature. We propose an
      approach to clinical diagnosis and treatment with oral azithromycin. 

PMID- 25398060
TI  - Bacillus Calmette-Guerin (BCG) infection following intravesical BCG
      administration as adjunctive therapy for bladder cancer: incidence, risk factors,
      and outcome in a single-institution series and review of the literature.
AB  - Bacillus Calmette-Guerin (BCG) is the most effective intravesical immunotherapy
      for superficial bladder cancer. Although generally well tolerated, BCG-related
      infectious complications may occur following instillation. Much of the current
      knowledge about this complication comes from single case reports, with
      heterogeneous diagnostic and therapeutic approaches and no investigation on risk
      factors for its occurrence. We retrospectively analyzed 256 patients treated with
      intravesical BCG in our institution during a 6-year period, with a minimum follow
      up of 6 months after the last instillation. We also conducted a comprehensive
      review and pooled analysis of additional cases reported in the literature since
      1975. Eleven patients (4.3%) developed systemic BCG infection in our institution,
      with miliary tuberculosis as the most common form (6 cases). A 3-drug
      antituberculosis regimen was initiated in all but 1 patient, with a favorable
      outcome in 9/10 cases. There were no significant differences in the mean number
      of transurethral resections prior to the first instillation, the time interval
      between both procedures, the overall mean number of instillations, or the
      presence of underlying immunosuppression between patients with or without BCG
      infection. We included 282 patients in the pooled analysis (271 from the
      literature and 11 from our institution). Disseminated (34.4%), genitourinary
      (23.4%), and osteomuscular (19.9%) infections were the most common presentations
      of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of
      cases, and the diagnostic performances for acid-fast staining, conventional
      culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and
      41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for
      a median of 6.0 (interquartile range: 4.0-9.0) months. Patients with disseminated
      infection more commonly received antituberculosis therapy and adjuvant
      corticosteroids, whereas those with reactive arthritis were frequently treated
      only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons).
      Attributable mortality was higher for patients aged >=65 years (7.4% vs 2.1%; p =
      0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and
      vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was
      resumed in only 2 of 36 patients with available data (5.6%), with an uneventful
      outcome. In the absence of an apparent predictor of the development of
      disseminated BCG infection after intravesical therapy, and considering the
      protean variety of clinical manifestations, it is essential to keep a high index
      of suspicion to initiate adequate therapy promptly and to evaluate carefully the
      risk-benefit balance of resuming intravesical BCG immunotherapy.

PMID- 25398063
TI  - Myocarditis in adult-onset still disease.
AB  - This study highlights the clinical features, treatments, and outcomes of the rare
      myocarditis in adult-onset Still disease (AOSD). Among a case series of 57
      patients fulfilling either Yamaguchi or Fautrel AOSD criteria and seen between
      1998 and 2010, we identified 4 cases of myocarditis. From a comprehensive
      literature review, we collected 20 additional cases of myocarditis-complicated
      AOSD. The characteristics of patients with myocarditis were compared with those
      of AOSD patients without myocarditis.In these 24 myocarditis-complicated AOSD
      cases, myocarditis occurred early and was present at AOSD onset in 54% of the
      cases. Myocarditis was often symptomatic (96% of patients) with nonspecific
      electrocardiographic abnormalities (79% of patients) and a left ventricle
      ejection fraction <=50% (67% of patients). Cardiac magnetic resonance imaging and
      endomyocardial biopsies showed features consistent with myocarditis in 4 patients
      and a mononuclear interstitial inflammatory infiltrate in 4 others. Steroids
      alone were effective in 50% of patients with myocarditis. Intravenous
      immunoglobulins, methotrexate, and tumor necrosis factor-alpha-blockers were also
      prescribed and often found effective. Only 1 patient died from cardiogenic shock.
      Patients with myocarditis-complicated AOSD were younger and more frequently male
      than patients with AOSD alone. Pericarditis was more frequent in the myocarditis
      group; white blood cell count, polymorphonuclear cell count, and serum ferritin
      levels were also higher.Myocarditis is a potentially life-threatening
      complication of AOSD but responds positively to steroids and other
      immunomodulatory drugs. Its prognosis remains good (only 1 death occurred), but
      the condition requires close monitoring of heart function. 

PMID- 25398064
TI  - Pauci-immune glomerulonephritis in individuals with disease associated with
      levamisole-adulterated cocaine: a series of 4 cases.
AB  - Exposure to levamisole-adulterated cocaine can induce a distinct clinical
      syndrome characterized by retiform purpura and/or agranulocytosis accompanied by
      an unusual constellation of serologic abnormalities including antiphospholipid
      antibodies, lupus anticoagulants, and very high titers of antineutrophil
      cytoplasmic antibodies. Two recent case reports suggest that levamisole
      adulterated cocaine may also lead to renal disease in the form of pauci-immune
      glomerulonephritis. To explore this possibility, we reviewed cases of pauci
      immune glomerulonephritis between 2010 and 2012 at an inner city safety net
      hospital where the prevalence of levamisole in the cocaine supply is known to be
      high. We identified 3 female patients and 1 male patient who had biopsy-proven
      pauci-immune glomerulonephritis, used cocaine, and had serologic abnormalities
      characteristic of levamisole-induced autoimmunity. Each also had some other form
      of clinical disease known to be associated with levamisole, either neutropenia or
      cutaneous manifestations. One patient had diffuse alveolar hemorrhage. Three of
      the 4 patients were treated with short courses of prednisone and
      cyclophosphamide, 2 of whom experienced stable long-term improvement in their
      renal function despite ongoing cocaine use. The remaining 2 patients developed
      end-stage renal disease and became dialysis-dependent. This report supports
      emerging concern of more wide spread organ toxicity associated with the use of
      levamisole-adulterated cocaine. 

PMID- 25398065
TI  - Klebsiella pneumoniae bloodstream infection: epidemiology and impact of
      inappropriate empirical therapy.
AB  - Multidrug resistance associated with extended-spectrum beta-lactamase (ESBL) and
      Klebsiella pneumoniae carbapenemase (KPC) among K. pneumoniae is endemic in
      southern Europe. We retrospectively analyzed the impact of resistance on the
      appropriateness of empirical therapy and treatment outcomes of K. pneumoniae
      bloodstream infections (BSIs) during a 2-year period at a 1420-bed tertiary-care
      teaching hospital in northern Italy. We identified 217 unique patient BSIs,
      including 92 (42%) KPC-positive, 49 (23%) ESBL-positive, and 1 (0.5%) metallo
      beta-lactamase-positive isolates. Adequate empirical therapy was administered in
      74% of infections caused by non-ESBL non-KPC strains, versus 33% of ESBL and 23%
      of KPC cases (p < 0.0001). To clarify the impact of resistance on BSI treatment
      outcomes, we compared several different models comprised of non-antibiotic
      treatment-related factors predictive of patients' 30-day survival status. Acute
      Physiology and Chronic Health Evaluation (APACHE) II score determined at the time
      of positive blood culture was superior to other investigated models, correctly
      predicting survival status in 83% of the study cohort. In multivariate analysis
      accounting for APACHE II, receipt of inadequate empirical therapy was associated
      with nearly a twofold higher rate of death (adjusted hazard ratio 1.9, 95%
      confidence interval 1.1-3.4; p = 0.02). Multidrug-resistant K. pneumoniae
      accounted for two-thirds of all K. pneumoniae BSIs, high rates of inappropriate
      empirical therapy, and twofold higher rates of patient death irrespective of
      underlying illness.

PMID- 25398067
TI  - HIV preexposure prophylaxis in the real world.
AB  - According to evolving guidelines, candidates for HIV preexposure prophylaxis
      (PrEP) include HIV-uninfected men who have sex with men who engage in condomless
      anal intercourse, individuals in HIV-serodifferent sexual relationships, those
      with frequent anogenital sexually transmitted infections, and those who have
      received repeated nonoccupational postexposure prophylaxis treatment courses. In
      the real-world setting, indications for PrEP and management of PrEP candidates
      and patients may be less than clear-cut. Factors to be considered when assessing
      candidacy for PrEP and maximizing efficacy of treatment are discussed. This
      article summarizes a presentation by Demetre C. Daskalakis, MD, MPH, at the IAS
      USA continuing education program held in Los Angeles, California, in April 2014. 

PMID- 25398068
TI  - Cardiovascular disease in HIV: traditional and nontraditional risk factors.
AB  - A new paradigm for atherogenesis in HIV infection is emerging, in which viral
      replication and microbial translocation result in ongoing T-cell and monocyte
      activation, with persistent inflammation leading to the development of atypical,
      high-risk morphology plaques. These plaques, characterized by low attenuation and
      positive remodeling, can be found even among HIV-infected patients who are at low
      risk for cardiovascular disease based on traditional risk factors. Prevention of
      cardiovascular events in HIV infection requires modulation of traditional risk
      factors and is also likely to require effective antiinflammatory treatment
      strategies. Statins, which are traditionally used to treat dyslipidemia, have
      also been shown to exert antiinflammatory effects associated with clinical
      benefit and may be useful to treat and prevent cardiovascular disease in HIV
      infected patients. However, large-scale studies of statins in the context of HIV
      infection must be conducted. This article summarizes a presentation by Steven K.
      Grinspoon, MD, at the IAS-USA continuing education program held in Chicago,
      Illinois, in May 2014. 

PMID- 25398066
TI  - Sex differences in patients receiving anticoagulant therapy for venous
      thromboembolism.
AB  - In patients with venous thromboembolism (VTE), the outcome during the course of
      anticoagulant therapy may differ according to the patient's sex. We used the
      RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to compare the
      rate of VTE recurrences, major bleeding, and mortality due to these events
      according to sex.As of August 2013, 47,499 patients were enrolled in RIETE, of
      whom 24,280 (51%) were women. Women were older, more likely presented with
      pulmonary embolism (PE), and were more likely to have recent immobilization but
      less likely to have cancer than men. During the course of anticoagulation (mean
      duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT),
      576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower
      rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]:
      0.67-0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83-1.15), a
      higher rate of major bleeding (HR: 1.21; 95% CI: 1.09-1.35), and higher mortality
      due to PE (HR: 1.24; 95% CI: 1.04-1.47). On multivariable analysis, any influence
      of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75-1.03), major
      bleeding (HR: 1.10; 95% CI: 0.98-1.24), or fatal PE (HR: 1.01; 95% CI: 0.84-1.22)
      was no longer statistically significant.In conclusion, women had fewer DVT
      recurrences and more bleeds than men during the course of anticoagulation. These
      differences were not due to sex, but very likely to other patient characteristics
      more common in female patients and differences in treatment choice.

PMID- 25398069
TI  - The skin and HIV: no superficial matter.
AB  - The vast majority of HIV-infected patients experience some type of skin disorder;
      these may broadly be categorized as infectious, neoplastic, or inflammatory.
      Additionally, primary pruritus afflicts a considerable percentage of HIV-infected
      individuals, and an attempt should be made to identify potential underlying
      triggers. Chronic itch, whether related to an underlying cutaneous, systemic, or
      psychiatric illness, can have a profound effect on quality of life. Therapy for
      inflammatory skin disorders may involve initiation of antiretroviral therapy in
      those who have not yet started such treatment, oral antihistamines, topical
      corticosteroids, topical antipruritic agents, and skin moisturizers. Because
      topical corticosteroids are often a necessary component of the therapeutic
      armamentarium for skin diseases, practitioners are encouraged to become familiar
      with the appropriate indications, strengths, and formulations of available
      preparations. In some instances, psychiatric medications or phototherapy may be
      necessary for the treatment of HIV-associated skin disorders, particularly for
      patients experiencing refractory itch. Although psoriasis is not more frequent
      among HIV-infected patients than in the general population, it can be more severe
      and debilitating for those who are HIV infected. Our understanding of psoriasis
      in the setting of HIV infection has evolved and new therapies for psoriasis have
      recently become available. This article summarizes a presentation by Sareeta R.
      S. Parker, MD, at the IAS-USA continuing education program held in Atlanta,
      Georgia, in April 2014. 

PMID- 25398070
TI  - Cirrhosis in hepatitis C virus-infected patients: a review for practitioners new
      to hepatitis C care.
AB  - Treatment of hepatitis C virus (HCV)-infected patients with cirrhosis remains
      challenging. Biopsy to stage liver fibrosis remains the standard for identifying
      cirrhosis, although the noninvasive technique of transient elastography is
      promising in this regard. Cirrhosis is categorized as compensated or
      decompensated, with the latter characterized by ascites, hepatic hydrothorax,
      bleeding varices, hepatic encephalopathy, and hepatorenal syndrome. In the
      interferon alfa treatment era, patients with compensated cirrhosis have been
      candidates for interferon alfa-based treatment, whereas those with decompensated
      cirrhosis have been treated with caution and only at a tertiary care or
      transplant center. New interferon alfa-free regimens offer safer treatment
      alternatives to patients with cirrhosis. Response to interferon alfa-based
      therapy alone and in combination with the first-generation HCV protease
      inhibitors boceprevir or telaprevir for the treatment of HCV genotype 1 infection
      has been poorer in patients with cirrhosis than in those without. With regimens
      that include newer direct-acting antivirals, response rates are tremendously
      improved for patients with cirrhosis but still slightly lower than those for
      patients without cirrhosis. As new regimens enter use outside of clinical trials,
      optimizing efficacy for patients with cirrhosis will be an important goal.
      Patients with cirrhosis must be taught to practice liver wellness following HCV
      cure, to lower the risk of progression of their liver disease. Risk of
      hepatocellular carcinoma also persists in patients with cirrhosis even if cure of
      HCV infection is achieved. The risk of these complications is dramatically
      reduced with cure of HCV infection through antiviral treatment. This article
      summarizes a presentation by Andrew J. Muir, MD, MHS, at the IAS-USA continuing
      education program held in Atlanta, Georgia, in September 2013. 

PMID- 25398071
TI  - Barriers and facilitators of Hispanic older adult mental health service
      utilization in the USA.
AB  - Mental health providers in the USA encounter the challenge and opportunity to
      engage the rapidly growing population of Hispanic older adults in evidence-based
      mental health treatments. This population underutilizes mental health services,
      despite comparable or slightly higher rates of mental illness compared with non
      Hispanic White older adults. This review identified barriers and facilitators of
      mental health service use by Hispanic older adults in the USA to identify
      practice, policy, and research implications. Hispanic older adults face multiple
      compounding barriers to mental health service use. Issues related to
      identification of needs, availability of services, accessibility of services, and
      acceptability of mental healthcare treatment are discussed. 

PMID- 25398073
TI  - Regional collaboration among Urban Area Security Initiative regions: results of
      the Johns Hopkins urban area survey.
AB  - Regional collaboration has been identified as a potential facilitator of public
      health preparedness efforts. The Urban Area Security Initiative (UASI) grant
      program, administered by the Federal Emergency Management Agency (FEMA) since
      2003, has provided 64 high-risk metropolitan areas funding to enhance their
      regional preparedness capabilities. This study describes informal and formal
      regional collaboration infrastructure, as well as regional collaboration-related
      activities and assessment methods, in FFY2010 UASI regions. A cross-sectional
      online survey was administered via Survey Monkey from September through December
      2013. Points of contact from FFY2010 funded UASI metropolitan areas completed the
      survey, with a response rate of 77.8% (n=49). Summary statistics were calculated
      to describe the current informal and formal regional collaboration
      infrastructure. Additionally, the cross-sectional survey collected rates of
      agreement with 8 collaborative preparedness statements at 3 time points. The
      survey found that UASI regions are engaging in collaborative activities and
      investments to build capabilities, with most collaboration occurring in the
      prevention, protection, and response mission areas. Collaborative relationships
      in preparedness among emergency managers and municipal chief executive officers
      improved during the FFY2010 UASI performance period compared to the pre-UASI
      award period, with lasting effects. The majority of UASI regions reported
      conducting independent assessments of capabilities and their measurement at the
      UASI region level. Urban areas that received a FFY2010 UASI grant award are
      engaging in collaborative activities and have established interjurisdictional
      relationships in preparedness. The use of grant funds to encourage collaboration
      in preparedness has the potential to leverage limited resources and promote
      informed investments. 

PMID- 25398072
TI  - Smoking-Specific Experiential Avoidance is Indirectly Associated with Trait Worry
      and Smoking Processes among Treatment-Seeking Smokers.
AB  - Limited work has examined worry, or apprehensive anticipation about future
      negative events, in terms of smoking. One potential explanatory factor is the
      tendency to respond inflexibly and with avoidance in the presence of smoking
      related distress (smoking-specific experiential avoidance). Participants (n =
      465) were treatment-seeking daily smokers. Cross-sectional (pre-treatment) self
      report data were utilized to assess trait worry, smoking-specific experiential
      avoidance, and four smoking criterion variables: nicotine dependence,
      motivational aspects of quitting, perceived barriers to smoking cessation, and
      severity of problematic symptoms reported in past quit attempts. Trait worry was
      significantly associated with greater levels of nicotine dependence, motivation
      to quit smoking, perceived barriers for smoking cessation, and more severe
      problems while quitting in the past; associations occurred indirectly through
      higher levels of smoking-specific experiential avoidance. Findings provide
      initial support for the potential role of smoking-specific experiential avoidance
      in explaining the association between trait worry and a variety of smoking
      processes.

PMID- 25398074
TI  - Lattice matching as the determining factor for molecular tilt and multilayer
      growth mode of the nanographene hexa-peri-hexabenzocoronene.
AB  - The microstructure, morphology, and growth dynamics of hexa-peri
      hexabenzocoronene (HBC, C42H18) thin films deposited on inert substrates of
      similar surface energies are studied with particular emphasis on the influence of
      substrate symmetry and substrate-molecule lattice matching on the resulting films
      of this material. By combining atomic force microscopy (AFM) with X-ray
      diffraction (XRD), X-ray absorption spectroscopy (NEXAFS), and in situ X-ray
      reflectivity (XRR) measurements, it is shown that HBC forms polycrystalline films
      on SiO2, where molecules are oriented in an upright fashion and adopt the known
      bulk structure. Remarkably, HBC films deposited on highly oriented pyrolytic
      graphite (HOPG) exhibit a new, substrate-induced polymorph, where all molecules
      adopt a recumbent orientation with planar pi-stacking. Formation of this new
      phase, however, depends critically on the coherence of the underlying graphite
      lattice since HBC grown on defective HOPG reveals the same orientation and phase
      as on SiO2. These results therefore demonstrate that the resulting film structure
      and morphology are not solely governed by the adsorption energy but also by the
      presence or absence of symmetry- and lattice-matching between the substrate and
      admolecules. Moreover, it highlights that weakly interacting substrates of high
      quality and coherence can be useful to induce new polymorphs with distinctly
      different molecular arrangements than the bulk structure.

PMID- 25398075
TI  - Compassion, guilt and innocence: An fMRI study of responses to victims who are
      responsible for their fate.
AB  - Compassion is a human feeling towards an individual who is suffering. However,
      the responses toward a victim are not always compassionate and may, for example,
      be moderated by the perceived responsibility of the victim. In the present study,
      we investigated the neural correlates of compassion and specifically
      differentiated the responses to other individuals' misfortunes depending on
      whether the victim was responsible for the event that occurred. In particular, we
      identified increased activation of the left insula, medial prefrontal cortex
      (mPFC), and adjacent anterior cingulate cortex when the participants read
      sentences with innocent compared with responsible victims. The reverse contrast
      revealed increased activation of the bilateral temporoparietal junction, right
      precuneus, and right dorsolateral prefrontal cortex (dlPFC). Using a psycho
      physiological interaction (PPI) analysis, we demonstrated that in the responsible
      condition, right dlPFC activation was accompanied by decreased activation in the
      left insula, anterior cingulate cortex (ACC), and mPFC. This inverse effective
      connectivity illustrates the antagonism of the dlPFC and mPFC in compassion
      related appraisal of external events. More specifically, our results imply that
      regulatory mechanisms of compassion are related to the perception of
      responsibility. 

PMID- 25398076
TI  - Construction and application of a Korean reference panel for imputing classical
      alleles and amino acids of human leukocyte antigen genes.
AB  - Genetic variations of human leukocyte antigen (HLA) genes within the major
      histocompatibility complex (MHC) locus are strongly associated with disease
      susceptibility and prognosis for many diseases, including many autoimmune
      diseases. In this study, we developed a Korean HLA reference panel for imputing
      classical alleles and amino acid residues of several HLA genes. An HLA reference
      panel has potential for use in identifying and fine-mapping disease associations
      with the MHC locus in East Asian populations, including Koreans. A total of 413
      unrelated Korean subjects were analyzed for single nucleotide polymorphisms
      (SNPs) at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1,
      and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs,
      233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino
      acid positions as binary variables. The imputation accuracy of the HLA reference
      panel was assessed by measuring concordance rates between imputed and genotyped
      alleles of the HLA genes from a subset of the study subjects and East Asian
      HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and
      4-digit allele resolutions, respectively. The imputation accuracy was minimally
      affected by SNP density of a test dataset for imputation. In conclusion, the
      Korean HLA reference panel we developed was highly suitable for imputing HLA
      alleles and amino acids from MHC SNPs in East Asians, including Koreans. 

PMID- 25398077
TI  - New developments in 2015 for Aging & Mental Health.

PMID- 25398078
TI  - Evaluation of sgRNA target sites for CRISPR-mediated repression of TP53.
AB  - The CRISPR (clustered regularly interspaced short palindromic repeats) platform
      has been developed as a general method to direct proteins of interest to gene
      targets. While the native CRISPR system delivers a nuclease that cleaves and
      potentially mutates target genes, researchers have recently employed
      catalytically inactive CRISPR-associated 9 nuclease (dCas9) in order to target
      and repress genes without DNA cleavage or mutagenesis. With the intent of
      improving repression efficiency in mammalian cells, researchers have also fused
      dCas9 with a KRAB repressor domain. Here, we evaluated different genomic sgRNA
      targeting sites for repression of TP53. The sites spanned a 200-kb distance,
      which included the promoter, transcript sequence, and regions flanking the
      endogenous human TP53 gene. We showed that repression up to 86% can be achieved
      with dCas9 alone (i.e., without use of the KRAB domain) by targeting the complex
      to sites near the TP53 transcriptional start site. This work demonstrates that
      efficient transcriptional repression of endogenous human genes can be achieved by
      the targeted delivery of dCas9. Yet, the efficiency of repression strongly
      depends on the choice of the sgRNA target site. 

PMID- 25398079
TI  - The Dose-Effect Relationship Between the Seeding Quantity of Human Marrow
      Mesenchymal Stem Cells and In Vivo Tissue-Engineered Bone Yield.
AB  - Although the feasibility of human bone marrow mesenchymal stem cell (hBMMSC)
      based tissue-engineered bone (TEB) has been proven in a number of studies,
      reaching a high positive fraction and bone yield of TEB still remains a
      challenge. Here we report a dose-effect relationship of the quantity of seeded
      cells with in vivo bone yield and the required quantity of hBMMSCs for the
      effective, stable bone formation of TEB. In our study, TEB was constructed using
      the static seeding technique with the gradient of seeding densities and volumes
      of passage 3 hBMMSCs. The in vitro characteristics of seeding efficiency,
      proliferation, viability, distribution, and osteogenic differentiation of hBMMSCs
      seeded on two commercial scaffolds of beta-TCP and CHA were investigated using
      alamarBlue assay, live/dead staining, confocal laser scanning microscope,
      scanning electronic microscopy examination, and mRNA expression analysis of
      osteogenic differentiation markers. After 3 months of ectopic implantation, in
      vivo bone regeneration was examined by quantitative analysis of histology and
      micro-CT. The results showed that 10 * 10(6) cells/ml was the minimum cell
      seeding density for CHA and beta-TCP to generate new bone in vivo. In addition,
      20 * 10(6) cells/ml and 30 * 10(6) cells/ml were the saturating seeding densities
      for CHA and beta-TCP to produce new bone effectively and stably, respectively.
      Thus, for different scaffolds, the saturating seeding density should be
      investigated first to ensure the effectiveness and stability of TEB construction
      with minimum donor injury, which is essential for the clinical application of
      TEB. 

PMID- 25398080
TI  - School Competence and Fluent Academic Performance: Informing Assessment of
      Educational Outcomes in Survivors of Pediatric Medulloblastoma.
AB  - Academic difficulties are widely acknowledged but not adequately studied in
      survivors of pediatric medulloblastoma. Although most survivors require special
      education services and are significantly less likely than healthy peers to finish
      high school, measured academic skills are typically average. This study sought to
      identify potential factors associated with academic difficulties in this
      population and focused on school competence and fluent academic performance.
      Thirty-six patients (ages 7-18 years old) were recruited through the Departments
      of Neurosurgery and Neuro-Oncology at Children's Medical Center Dallas and Cook
      Children's Medical Center in Fort Worth, TX. Participants completed a
      neuropsychological screening battery including selected Woodcock-Johnson III
      Tests of Achievement subtests. Parents completed the Child Behavior Checklist.
      School competence was significantly correlated with measured academic skills and
      fluency. Basic academic skill development was broadly average, in contrast to
      significantly worse fluent academic performance. School competence may have
      utility as a measure estimating levels of educational success in this population.
      Additionally, academic difficulties experienced by childhood medulloblastoma
      survivors may be better captured by measuring deficits in fluent academic
      performance rather than skills. Identification of these potential factors
      associated with educational outcomes of pediatric medulloblastoma survivors has
      significant implications for research, clinical assessment, and academic
      services/interventions. 

PMID- 25398081
TI  - Complete chloroplast genome sequence of Omani lime (Citrus aurantiifolia) and
      comparative analysis within the rosids.
AB  - The genus Citrus contains many economically important fruits that are grown
      worldwide for their high nutritional and medicinal value. Due to frequent
      hybridizations among species and cultivars, the exact number of natural species
      and the taxonomic relationships within this genus are unclear. To compare the
      differences between the Citrus chloroplast genomes and to develop useful genetic
      markers, we used a reference-assisted approach to assemble the complete
      chloroplast genome of Omani lime (C. aurantiifolia). The complete C.
      aurantiifolia chloroplast genome is 159,893 bp in length; the organization and
      gene content are similar to most of the rosids lineages characterized to date.
      Through comparison with the sweet orange (C. sinensis) chloroplast genome, we
      identified three intergenic regions and 94 simple sequence repeats (SSRs) that
      are potentially informative markers with resolution for interspecific
      relationships. These markers can be utilized to better understand the origin of
      cultivated Citrus. A comparison among 72 species belonging to 10 families of
      representative rosids lineages also provides new insights into their chloroplast
      genome evolution. 

PMID- 25398082
TI  - Impact of NGO training and support intervention on diarrhoea management practices
      in a rural community of Bangladesh: an uncontrolled, single-arm trial.
AB  - PURPOSE/OBJECTIVE: The evolving Non-Governmental Organization (NGO) sector in
      Bangladesh provides health services directly, however some NGOs indirectly
      provide services by working with unlicensed providers. The primary objective of
      this study was to examine the impact of NGO training of unlicensed providers on
      diarrhoea management and the scale up of zinc treatment in rural populations.
      METHODS: An uncontrolled, single-arm trial for a training and support
      intervention on diarrhoea outcomes was employed in a rural sub-district of
      Bangladesh during 2008. Two local NGOs and their catchment populations were
      chosen for the study. The intervention included training of unlicensed health
      care providers in the management of acute childhood diarrhoea, particularly
      emphasizing zinc treatment. In addition, community-based promotion of zinc
      treatment was carried out. Baseline and endline ecologic surveys were carried out
      in intervention and control villages to document changes in treatments received
      for diarrhoea in under-five children. RESULTS: Among surveyed household with an
      active or recent acute childhood diarrhoea episode, 69% sought help from a health
      provider. Among these, 62.8% visited an unlicensed private provider. At baseline,
      23.9% vs. 22% of control and intervention group children with diarrhoea had
      received zinc of any type. At endline (6 months later) this had changed to 15.3%
      vs. 30.2%, respectively. The change in zinc coverage was significantly higher in
      the intervention villages (p<0.01). Adherence with giving zinc for 10 days or
      more was significantly higher in the intervention households (9.2% vs. 2.5%;
      p<0.01). Child's age, duration of diarrhoea, type of diarrhoea, parental year of
      schooling as well as oral rehydration solution (ORS) and antibiotic usage were
      significant predictors of zinc usage. CONCLUSION: Training of unlicensed
      healthcare providers through NGOs increased zinc coverage in the diarrhoea
      management of under-five children in rural Bangladesh households. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02143921.

PMID- 25398083
TI  - Gender-related differences in cardiometabolic risk profile of Japanese patients
      with diabetes.
AB  - BACKGROUND: In patients with diabetes, cardiovascular disease is an important
      determinant of their prognosis. The aim of this study was to compare
      cardiometabolic risk factors in Japanese women and men with diabetes. METHODS:
      The subjects were Japanese patients with diabetes, and age-matched female and
      male subject groups with the ratio of number of women to that of men being 1 to 2
      were prepared (total number of subjects, 1,707; mean age, 53.8 years).
      Cardiometabolic risk factors were compared in women and men. RESULTS: Waist-to
      height ratio was significantly higher in the female group than in the male group,
      while body mass index was not significantly different in the two groups.
      Diastolic blood pressure and pulse pressure were significantly lower and higher,
      respectively, in the female group than in the male group, while systolic blood
      pressure was not significantly different in the two groups. Low-density
      lipoprotein cholesterol and log-transformed triglycerides were significantly
      higher and lower, respectively, in the female group than in the male group. Log
      transformed lipid accumulation product was significantly higher in the female
      group than in the male group. Odds ratios (with their 95% confidence intervals
      [95% CIs]) of gender (women vs. men) were 2.00 [95% CI: 1.48 to 2.69] for
      abdominal obesity, 1.48 [95% CI: 1.15 to 1.91]) for high pulse pressure, 1.48
      [95% CI: 1.13 to 1.92] for high low-density lipoprotein cholesterolemia, 1.77
      [95% CI: 1.32 to 2.37] for low high-density lipoprotein cholesterolemia, and 1.68
      [95% CI: 1.28 to 2.21] for metabolic syndrome diagnosed by the International
      Diabetes Federation criteria. Thus, women had significantly higher odds for these
      cardiovascular risk factors than did men. CONCLUSION: The results suggest that
      Japanese women with diabetes have a more adverse cardiometabolic profile than do
      men.

PMID- 25398085
TI  - Raman and IR studies of pressure- and temperature-induced phase transitions in
      [(CH2)3NH2][Zn(HCOO)3].
AB  - Temperature- and pressure-dependent studies of Raman and IR spectra have been
      performed on azetidinium zinc formate, [(CH2)3NH2][Zn(HCOO)3]. Vibrational
      spectra showed distinct anomalies in mode frequencies and bandwidths near 250 and
      300 K, which were attributed to structural phase transitions associated with the
      gradual freezing of ring-puckering motions of the azetidinium cation. Pressure
      dependent studies revealed a pressure-induced transition near 0.4 GPa. Raman
      spectra indicate that the structure of the room-temperature intermediate phase
      observed near 0.4 GPa is the same as the monoclinic structure observed at ambient
      pressure below 250 K. The second phase transition was found near 2.4 GPa. This
      transition has strong first-order character and is associated with strong
      distortion of both the zinc formate framework and azetidinium cations. The last
      phase transition was found near 7.0 GPa. This transition leads to lowering of the
      symmetry and further distortion of the zinc formate framework, whereas the
      azetidinium cation structure is weakly affected. 

PMID- 25398084
TI  - Disclosure of genetic information and change in dietary intake: a randomized
      controlled trial.
AB  - BACKGROUND: Proponents of consumer genetic tests claim that the information can
      positively impact health behaviors and aid in chronic disease prevention.
      However, the effects of disclosing genetic information on dietary intake behavior
      are not clear. METHODS: A double-blinded, parallel group, 2:1 online randomized
      controlled trial was conducted to determine the short- and long-term effects of
      disclosing nutrition-related genetic information for personalized nutrition on
      dietary intakes of caffeine, vitamin C, added sugars, and sodium. Participants
      were healthy men and women aged 20-35 years (n = 138). The intervention group (n
      = 92) received personalized DNA-based dietary advice for 12-months and the
      control group (n = 46) received general dietary recommendations with no genetic
      information for 12-months. Food frequency questionnaires were collected at
      baseline and 3- and 12-months after the intervention to assess dietary intakes.
      General linear models were used to compare changes in intakes between those
      receiving general dietary advice and those receiving DNA-based dietary advice.
      RESULTS: Compared to the control group, no significant changes to dietary intakes
      of the nutrients were observed at 3-months. At 12-months, participants in the
      intervention group who possessed a risk version of the ACE gene, and were advised
      to limit their sodium intake, significantly reduced their sodium intake (mg/day)
      compared to the control group (-287.3 +/- 114.1 vs. 129.8 +/- 118.2, p = 0.008).
      Those who had the non-risk version of ACE did not significantly change their
      sodium intake compared to the control group (12-months: -244.2 +/- 150.2, p =
      0.11). Among those with the risk version of the ACE gene, the proportion who met
      the targeted recommendation of 1500 mg/day increased from 19% at baseline to 34%
      after 12 months (p = 0.06). CONCLUSIONS: These findings demonstrate that
      disclosing genetic information for personalized nutrition results in greater
      changes in intake for some dietary components compared to general population
      based dietary advice. TRIAL REGISTRATION: ClinicalTrials.gov NCT01353014.

PMID- 25398086
TI  - High parental monitoring prevents adolescents from engaging in risky sexual
      practices in Harar, Ethiopia.
AB  - BACKGROUND: Emerging findings have shown that high parental monitoring of
      adolescents' sexual and reproductive health (SRH) communications between parents
      and adolescents and good parenting styles prevent adolescents from engaging in
      risky sexual practices. OBJECTIVE: The aim of this study was to examine the
      associations of parental monitoring, parent-adolescent SRH communications, and
      parenting styles with risky sexual practices among adolescents in Harar,
      Ethiopia. DESIGNS: This was a cross-sectional study conducted on adolescents aged
      13-18 who had sexual initiations. Adolescents who failed to use any contraceptive
      method and/or condom during last sexual intercourse and who experienced multiple
      sexual partners in the 12 months prior to the study were taken as 'at risk'. In
      view of these, the adolescents risk count ranged from zero to three--greater
      number indicates higher count of risky sexual practices. Poisson regression model
      was used to examine the associations and p<0.05 indicated a statistical
      significance. RESULTS: It was found out that 301 of 633 (47.55%; 95% CI=43.62%,
      51.45%) adolescents experienced one or more risky sexual practices. High parental
      monitoring compared to low decreases the Incidence Rate of engaging in risky
      sexual practices by 28% (adjusted incidence rate ratio, or IRR=0.72; 95%
      CI=0.520, 0.986). Those who had a satisfactory level of SRH communications with
      their parents compared to poor communicators experianced less incidence rate of
      risky sexual practices which was marginal (adjusted IRR=0.82; 95% CI=0.637,
      1.051). CONCLUSIONS: A significant proportion of the adolescents engaged in one
      or more risky sexual practices. Importantly, high parental monitoring decreases
      the likelihood of these risky practices. Therefore, parents need to be encouraged
      to keep an eye on their young children.

PMID- 25398087
TI  - A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with
      higher protective efficacy against tuberculosis.
AB  - Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis
      (Mtb) that is a major public health problem. The vaccine used for TB prevention
      is Mycobacterium bovis bacillus Calmette-Guerin (BCG), which provides variable
      efficacy in protecting against pulmonary TB among adults. Consequently, several
      groups have pursued the development of a new vaccine with a superior protective
      capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine
      expressing a fusion protein (CMX) composed of immune dominant epitopes from
      Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a
      murine model of infection. The stability of the vaccine in vivo was maintained
      for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by
      peritoneal macrophages and induced nitric oxide (NO) production. Following mouse
      immunization, this vaccine induced a specific immune response in cells from lungs
      and spleen to the fusion protein and to each of the component recombinant
      proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17,
      and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension
      of lung lesions caused by challenge with Mtb as well as the lung bacterial load.
      In addition, when this vaccine was used in a prime-boost strategy together with
      rCMX, the lung bacterial load was lower than the result observed by BCG
      vaccination. This study describes the creation of a new promising vaccine for TB
      that we hope will be used in further studies to address its safety before
      proceeding to clinical trials. 

PMID- 25398089
TI  - Positive relationship between serum low-density lipoprotein cholesterol levels
      and visceral fat in a Chinese nondiabetic population.
AB  - BACKGROUND: It has been reported that obesity and serum low-density lipoprotein
      cholesterol (LDL-c) are important risk factors of cardiovascular disease (CVD).
      It is recognized that regionalized adiposity has different cardiovascular risk,
      visceral versus subcutaneous, is a better predictor of CVD. However, the
      relationship between regionalized adiposity and LDL-c is unclear. The present
      study was designed to investigate the relationship between visceral fat
      accumulation and serum LDL-c levels in a Chinese cohort. METHODS: A total of 1
      538 subjects (539 men, 999 women; 20-75 years old) with normal glucose tolerance
      and blood pressure were recruited. All subjects underwent magnetic resonance
      imaging to quantify visceral fat area (VFA) and subcutaneous fat area. Serum LDL
      c levels were detected by direct assay method. RESULTS: Overweight/obese subjects
      (body mass index (BMI) >= 25 kg/m2) had significantly higher serum LDL-c levels
      than the lean subjects (BMI <25 kg/m2) (P < 0.01). An increasing trend in serum
      LDL-c levels was found to accompany the increase in VFA (P for trend < 0.01).
      Within the same BMI category, subjects with abdominal obesity (VFA >= 80 cm2) had
      significantly higher LDL-c levels than those without abdominal obesity (VFA < 80
      cm2) (P < 0.05). Multiple stepwise regression analysis showed that increased VFA
      was an independent risk factor for elevated LDL-c levels, not only in the entire
      study population (Standard beta = 0.138; P < 0.01), but also when the study
      population was subdivided into men, premenopausal and postmenopausal women
      (Standard beta = 0.117, 0.145, 0.090 respectively for men, premenopausal women,
      postmenopausal women; all P < 0.01). CONCLUSIONS: VFA was positively correlated
      with serum LDL-c levels in a nondiabetic Chinese population with normal blood
      pressure.

PMID- 25398088
TI  - Magnetic resonance imaging (MRI) to study striatal iron accumulation in a rat
      model of Parkinson's disease.
AB  - Abnormal accumulation of iron is observed in neurodegenerative disorders. In
      Parkinson's disease, an excess of iron has been demonstrated in different
      structures of the basal ganglia and is suggested to be involved in the
      pathogenesis of the disease. Using the 6-hydroxydopamine (6-OHDA) rat model of
      Parkinson's disease, the edematous effect of 6-OHDA and its relation with
      striatal iron accumulation was examined utilizing in vivo magnetic resonance
      imaging (MRI). The results revealed that in comparison with control animals,
      injection of 6-OHDA into the rat striatum provoked an edematous process, visible
      in T2-weighted images that was accompanied by an accumulation of iron clearly
      detectable in T2*-weighted images. Furthermore, Prussian blue staining to detect
      iron in sectioned brains confirmed the existence of accumulated iron in the areas
      of T2* hypointensities. The presence of ED1-positive microglia in the lesioned
      striatum overlapped with this accumulation of iron, indicating areas of toxicity
      and loss of dopamine nerve fibers. Correlation analyses demonstrated a direct
      relation between the hyperintensities caused by the edema and the hypointensities
      caused by the accumulation of iron. 

PMID- 25398090
TI  - Evaluation of antibody response of killed and live vaccines against porcine
      epidemic diarrhea virus in a field study.
AB  - BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an infectious, highly
      contagious virus, and is an etiological agent of acute entero-pathogenic diarrhea
      in swine. OBJECTIVES: Evaluation of the antibody response of two types of PEDV
      vaccines is to be carried out. ANIMALS AND METHODS: Sows were vaccinated with
      either live or killed commercial PEDV SM98 (GenBank: GU937797.1) vaccines. Four
      different groups of sows with five sows in each group were used in this study:
      the unvaccinated negative control group, the killed virus vaccination group with
      killed virus boosting (K/K), the live virus vaccinated group with live virus
      boosting (L/L), and the combination group vaccinated with live virus and
      subsequently boosted with killed vaccine (L/K). Sows were vaccinated
      intramuscularly twice at four and two weeks prior to farrowing with 2ml/head
      vaccine dose. Antibody titers in sow and piglet serum one week after farrowing
      and that in colostrum were compared by enzyme-linked immunosorbent assay (ELISA)
      and serum neutralization test. RESULTS: Vaccination with K/K vaccine induced the
      highest level of IgG and IgA in sow serum, colostrum, and especially in piglet
      serum, with the lowest levels found in the L/L group. The major neutralizing
      activity was also found in the K/K group, particularly in colostrum, with piglets
      bearing higher neutralizing activity compared to sow sera. Among recombinant
      spike S1, S2, S3, and nucleocapsid N protein of PEDV, S3 protein presented the
      highest antibody level in the K/K group. CONCLUSION: Killed PEDV SM98 vaccine
      induced higher antibody levels. CLINICAL IMPORTANCE: This study clearly confirms
      that killed vaccine has induced higher antibody levels and may contribute to the
      design of future research and vaccine programs.

PMID- 25398091
TI  - High diversity and low specificity of chaetothyrialean fungi in carton galleries
      in a neotropical ant-plant association.
AB  - New associations have recently been discovered between arboreal ants that live on
      myrmecophytic plants, and different groups of fungi. Most of the - usually
      undescribed - fungi cultured by the ants belong to the order Chaetothyriales
      (Ascomycetes). Chaetothyriales occur in the nesting spaces provided by the host
      plant, and form a major part of the cardboard-like material produced by the ants
      for constructing nests and runway galleries. Until now, the fungi have been
      considered specific to each ant species. We focus on the three-way association
      between the plant Tetrathylacium macrophyllum (Salicaceae), the ant Azteca brevis
      (Formicidae: Dolichoderinae) and various chaetothyrialean fungi. Azteca brevis
      builds extensive runway galleries along branches of T. macrophyllum. The carton
      of the gallery walls consists of masticated plant material densely pervaded by
      chaetothyrialean hyphae. In order to characterise the specificity of the ant
      fungus association, fungi from the runway galleries of 19 ant colonies were grown
      as pure cultures and analyzed using partial SSU, complete ITS, 5.8S and partial
      LSU rDNA sequences. This gave 128 different fungal genotypes, 78% of which were
      clustered into three monophyletic groups. The most common fungus (either genotype
      or approximate species-level OTU) was found in the runway galleries of 63% of the
      investigated ant colonies. This indicates that there can be a dominant fungus
      but, in general, a wider guild of chaetothyrialean fungi share the same ant
      mutualist in Azteca brevis. 

PMID- 25398094
TI  - Regulatory T cell activity is partly inhibited in a mouse model of chronic
      Pseudomonas aeruginosa lung infection.
AB  - OBJECTIVES: We aimed to investigate the activity of regulatory T (Treg) cells in
      chronic Pseudomonas aeruginosa (PA) lung infection and its influence on effector
      T-cell responses. MATERIALS AND METHODS: C57BL/6 mice were randomly inoculated
      with PA-laden agarose beads (1 * 10(5) CFU/50 MUL) or planktonic PA (1 * 10(5)
      CFU/50 MUL), and euthanized at the time points of 4 hour, day 1, 3, 5, and 7.
      Bacterial load, bronchoalveolar lavage (BAL) fluid cell counts, and lung tissue
      histology were assessed. BAL fluid concentrations of TGF-beta1, IFN-gamma, IL
      1beta, IL-4, IL-6, IL-10, and IL-17A were measured. Messenger RNA (mRNA) levels
      of TGF-beta1, IL-10 and CD4(+) T-cell subtype-specific transcription factors were
      determined. The expression of CD4(+)CD25(+)forkhead box P3 (FoxP3)(+) cells in
      lungs and spleens were analyzed. RESULTS: Mice inoculated with PA-laden agarose
      beads developed chronic PA lung infection during 7-day study period, while mice
      inoculated with planktonic PA cleared bacteria in 3 days. Compared with mice
      recovered from acute PA lung infection, those with chronic infection had
      significantly increased effector T-cell responses, accompanied by a more severe
      neutrophilic inflammation. Mice with chronic PA lung infection had significantly
      lower concentration of TGF-beta1 and higher concentrations of IFN-gamma, IL
      1beta, IL-6, and IL-17A in BAL fluid. Meanwhile, they had significantly lower
      mRNA levels of TGF-beta1, IL-10 and FoxP3 in lung tissues, and lower expression
      of CD4(+)CD25(+)FoxP3(+) cells in lungs and spleens. CONCLUSIONS: These findings
      indicate that Treg cell activity is partly inhibited in mice with chronic PA lung
      infection, which contributes to the enhanced effector T-cell responses in
      airways.

PMID- 25398095
TI  - Can vibrations control drop motion?
AB  - We discuss a mechanism for controlled motion of drops with applications for
      microfluidics and microgravity. The mechanism is the following: a solid plate
      supporting a liquid droplet is simultaneously subject to lateral and vertical
      harmonic oscillations. In this way the symmetry of the back-and-forth droplet
      movement along the substrate under inertial effects is broken and thus will
      induce a net driven motion of the drop. We study the dependency of the traveled
      distance on the oscillation parameters (forcing amplitude, frequency, and phase
      shift between the two perpendicular oscillations) via phase field simulations.
      The internal flow structure inside the droplet is also investigated. We make
      predictions on resonance frequencies for drops on a substrate with a varying
      wettability. 

PMID- 25398092
TI  - Integrin expression in esophageal squamous cell carcinoma: loss of the
      physiological integrin expression pattern correlates with disease progression.
AB  - The integrins are a family of heterodimeric transmembrane signaling receptors
      that mediate the adhesive properties of epithelial cells affecting cell growth
      and differentiation. In many epithelial malignancies, altered integrin expression
      is associated with tumor progression and often correlates with unfavorable
      prognosis. However, only few studies have investigated the role of integrin
      expression in esophageal squamous cell carcinoma (ESCC). Using a novel
      quantifying immunofluorescence-staining assay, we investigated the expression of
      the integrins alpha2beta1, alpha3beta1, alpha6beta1, and alpha6beta4 in primary
      ESCC of 36 patients who underwent surgical resection. Magnitude and distribution
      of expression were analyzed in primary tumor samples and autologous esophageal
      squamous epithelium. The persistence of the physiologically polarized expression
      of the subunits alpha6, beta1, and beta4 in the tumor tissue was significantly
      associated with prolonged relapse-free survival (p = 0.028, p = 0.034, p =
      0.006). In contrast, patients with reduced focal alpha6 expression at the tumor
      invasion front shared a significantly shortened relapse-free survival compared to
      patients with strong alpha6 expression at their stromal surfaces, as it was
      regularly observed in normal esophageal epithelium (p = 0.001). Multivariate
      regression analysis identified the maintenance of strong alpha6 immunoreactivity
      at the invasion front as an independent prognostic factor for increased relapse
      free and disease-specific survival (p = 0.003; p = 0.003). Our findings suggest
      that alterations in both pattern and magnitude of integrin expression may play a
      major role in the disease progression of ESCC patients. Particularly, the
      distinct expression of the integrins alpha6beta4 and alpha6beta1 at the invasion
      front as well as the maintenance of a polarized integrin expression pattern in
      the tumor tissue may serve as valuable new markers to assess the aggressiveness
      of ESCC. 

PMID- 25398097
TI  - Asymmetric hydroformylation-initiated tandem sequences for syntheses of (+)
      patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-prelog djerassi
      lactone.
AB  - Four different Rh-catalyzed asymmetric hydroformylation (AHF) tandem reactions
      have been developed in the context of the total syntheses of (+)-patulolide C, (
      )-pyrenophorol, (+)-decarestrictine L, and (+)-Prelog-Djerassi lactone. A total
      synthesis of (+)-patulolide C has been accomplished in three steps utilizing a
      Rh(I)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of a known alkyne
      to give a Z-enol acetate with excellent selectivity. An AHF/intramolecular Wittig
      olefination cascade was utilized to set the C4-hydroxyl stereochemistry, E-olefin
      geometry, and form the macrolactone. In addition, both (-)-pyrenophorol and (+)
      decarestrictine L have been synthesized from the enantiomeric (4R)- and (4S)-4
      (tert-butyldimethylsiloxy)-1-pentyne in five and four steps, respectively. These
      syntheses feature Ru(II)-catalyzed Z-selective anti-Markovnikov
      hydroacetoxylation of terminal alkynes followed by AHF/Wittig olefination
      sequences to rapidly establish functionality and stereogenicity. A synthesis of
      (+)-Prelog-Djerassi lactone was accomplished in three isolations from the known 1
      vinyl-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane ortho ester. An AHF/crotylation
      tandem sequence has been developed to set the C2-C4 stereochemistry. An
      asymmetric hydrogenation was employed to set the C6 stereochemistry, resulting in
      an especially efficient enantioselective synthesis from achiral starting
      material. In summary, these syntheses have greatly improved efficiency in terms
      of atom-economy, catalytic stereoselective transformations, inexpensive reagents,
      step-counts, and overall yield when compared with previous synthetic attempts. 

PMID- 25398096
TI  - Sequencing, annotation and analysis of the Syrian hamster (Mesocricetus auratus)
      transcriptome.
AB  - BACKGROUND: The Syrian hamster (golden hamster, Mesocricetus auratus) is gaining
      importance as a new experimental animal model for multiple pathogens, including
      emerging zoonotic diseases such as Ebola. Nevertheless there are currently no
      publicly available transcriptome reference sequences or genome for this species.
      RESULTS: A cDNA library derived from mRNA and snRNA isolated and pooled from the
      brains, lungs, spleens, kidneys, livers, and hearts of three adult female Syrian
      hamsters was sequenced. Sequence reads were assembled into 62,482 contigs and
      111,796 reads remained unassembled (singletons). This combined contig/singleton
      dataset, designated as the Syrian hamster transcriptome, represents a total of
      60,117,204 nucleotides. Our Mesocricetus auratus Syrian hamster transcriptome
      mapped to 11,648 mouse transcripts representing 9,562 distinct genes, and mapped
      to a similar number of transcripts and genes in the rat. We identified 214 quasi
      complete transcripts based on mouse annotations. Canonical pathways involved in a
      broad spectrum of fundamental biological processes were significantly represented
      in the library. The Syrian hamster transcriptome was aligned to the current
      release of the Chinese hamster ovary (CHO) cell transcriptome and genome to
      improve the genomic annotation of this species. Finally, our Syrian hamster
      transcriptome was aligned against 14 other rodents, primate and laurasiatheria
      species to gain insights about the genetic relatedness and placement of this
      species. CONCLUSIONS: This Syrian hamster transcriptome dataset significantly
      improves our knowledge of the Syrian hamster's transcriptome, especially towards
      its future use in infectious disease research. Moreover, this library is an
      important resource for the wider scientific community to help improve genome
      annotation of the Syrian hamster and other closely related species. Furthermore,
      these data provide the basis for development of expression microarrays that can
      be used in functional genomics studies.

PMID- 25398098
TI  - High-throughput chemical modification of oligonucleotides for systematic
      structure-activity relationship evaluation.
AB  - Chemical modification of siRNA is achieved in a high-throughput manner (96-well
      plate format) by copper catalyzed azide-alkyne cycloadditions. This
      transformation can be performed in one synthetic operation at up to four
      positions with complete specificity, good yield, and acceptable purity. As
      demonstrated here, this approach extends the current synthetic options for
      oligonucleotide modifications and simultaneously facilitates the systematic,
      rapid biological evaluation of modified siRNA. 

PMID- 25398100
TI  - Modulation of surface trap induced resistive switching by electrode annealing in
      individual PbS micro/nanowire-based devices for resistance random access memory.
AB  - Bipolar resistive switching (RS) devices are commonly believed as a promising
      candidate for next generation nonvolatile resistance random access memory (RRAM).
      Here, two-terminal devices based on individual PbS micro/nanowires with Ag
      electrodes are constructed, whose electrical transport depends strongly on the
      abundant surface and bulk trap states in micro/nanostructures. The surface trap
      states can be filled/emptied effectively at negative/positive bias voltage,
      respectively, and the corresponding rise/fall of the Fermi level induces a
      variation in a degenerate/nondegenerate state, resulting in low/high resistance.
      Moreover, the filling/emptying of trap states can be utilized as RRAM. After
      annealing, the surface trap state can almost be eliminated completely; while most
      of the bulk trap states can still remain. In the devices unannealed and annealed
      at both ends, therefore, the symmetrical back-to-back Fowler-Nordheim tunneling
      with large ON/OFF resistance ratio and Poole-Frenkel emission with poor
      hysteresis can be observed under cyclic sweep voltage, respectively. However, a
      typical bipolar RS behavior can be observed effectively in the devices annealed
      at one end. The acquirement of bipolar RS and nonvolatile RRAM by the modulation
      of electrode annealing demonstrates the abundant trap states in
      micro/nanomaterials will be advantageous to the development of new type
      electronic components. 

PMID- 25398099
TI  - Delirium, sedation and analgesia in the intensive care unit: a multinational, two
      part survey among intensivists.
AB  - Analgesia, sedation and delirium management are important parts of intensive care
      treatment as they are relevant for patients' clinical and functional long-term
      outcome. Previous surveys showed that despite this fact implementation rates are
      still low. The primary aim of the prospective, observational multicenter study
      was to investigate the implementation rate of delirium monitoring among
      intensivists. Secondly, current practice concerning analgesia and sedation
      monitoring as well as treatment strategies for patients with delirium were
      assesed. In addition, this study compares perceived and actual practice regarding
      delirium, sedation and analgesia management. Data were obtained with a two-part,
      anonymous survey, containing general data from intensive care units in a first
      part and data referring to individual patients in a second part. Questionnaires
      from 101 hospitals (part 1) and 868 patients (part 2) were included in data
      analysis. Fifty-six percent of the intensive care units reported to monitor for
      delirium in clinical routine. Fourty-four percent reported the use of a validated
      delirium score. In this respect, the survey suggests an increasing use of
      delirium assessment tools compared to previous surveys. Nevertheless, part two of
      the survey revealed that in actual practice 73% of included patients were not
      monitored with a validated score. Furthermore, we observed a trend towards
      moderate or deep sedation which is contradicting to guideline-recommendations.
      Every fifth patient was suffering from pain. The implementation rate of adequate
      pain-assessment tools for mechanically ventilated and sedated patients was low
      (30%). In conclusion, further efforts are necessary to implement guideline
      recommendations into clinical practice. The study was registered
      (ClinicalTrials.gov identifier: NCT01278524) and approved by the ethical
      committee. 

PMID- 25398101
TI  - Methods for determining the uncertainty of population estimates derived from
      satellite imagery and limited survey data: a case study of Bo city, Sierra Leone.
AB  - This study demonstrates the use of bootstrap methods to estimate the total
      population of urban and periurban areas using satellite imagery and limited
      survey data. We conducted complete household surveys in 20 neighborhoods in the
      city of Bo, Sierra Leone, which collectively were home to 25,954 persons living
      in 1,979 residential structures. For five of those twenty sections, we quantized
      the rooftop areas of structures extracted from satellite images. We used
      bootstrap statistical methods to estimate the total population of the pooled
      sections, including the associated uncertainty intervals, as a function of sample
      size. Evaluations based either on rooftop area per person or on the mean number
      of occupants per residence both converged on the true population size. We
      demonstrate with this simulation that demographic surveys of a relatively small
      proportion of residences can provide a foundation for accurately estimating the
      total population in conjunction with aerial photographs. 

PMID- 25398102
TI  - Bringing in the cavalry: IL-26 mediates neutrophil recruitment to the lungs.

PMID- 25398103
TI  - Sepsis biomarkers. Value and limitations.

PMID- 25398104
TI  - Narrowing in on early cystic fibrosis lung disease.

PMID- 25398105
TI  - MARCKS is marked in combating lung cancer growth and acquired resistance.

PMID- 25398107
TI  - REM sleep: a nightmare for patients with obstructive sleep apnea?

PMID- 25398106
TI  - Back to the future: alpha-hemolysin activity on blood agar to predict ventilator
      associated pneumonia caused by Staphylococcus aureus.

PMID- 25398108
TI  - Acute respiratory distress syndrome: emerging research in China.

PMID- 25398109
TI  - Getting a better picture of the correlation between lung function and structure
      using electrical impedance tomography.

PMID- 25398110
TI  - NOS1: a susceptibility gene for reduced level of FEV1 in the setting of pesticide
      exposure.

PMID- 25398111
TI  - Proximity to a major road, vitamin D insufficiency, and severe asthma
      exacerbations in Puerto Rican children.

PMID- 25398112
TI  - Native and active vitamin D in intensive care: who and how we treat is crucially
      important.

PMID- 25398113
TI  - Reply: active and native vitamin D in critical illness.

PMID- 25398114
TI  - A few follow-up questions to a recent calcitriol and sepsis study.

PMID- 25398115
TI  - Proper reading of pulmonary artery vascular pressure tracings.

PMID- 25398116
TI  - Reply: reading of pulmonary artery pressure tracings: the best compromise of
      accuracy and clinical pertinence.

PMID- 25398118
TI  - Expression of concern: decline in NRF2-regulated antioxidants in COPD lungs due
      to loss of its positive regulator, and heightened endoplasmic reticulum stress in
      the lungs of patients with COPD.

PMID- 25398119
TI  - An official American Thoracic Society statement: diagnosis and management of
      beryllium sensitivity and chronic beryllium disease.
AB  - RATIONALE: Beryllium continues to have a wide range of industrial applications.
      Exposure to beryllium can lead to sensitization (BeS) and chronic beryllium
      disease (CBD). OBJECTIVES: The purpose of this statement is to increase awareness
      and knowledge about beryllium exposure, BeS, and CBD. METHODS: Evidence was
      identified by a search of MEDLINE. The committee then summarized the evidence,
      drew conclusions, and described their approach to diagnosis and management. MAIN
      RESULTS: The beryllium lymphocyte proliferation test is the cornerstone of both
      medical surveillance and the diagnosis of BeS and CBD. A confirmed abnormal
      beryllium lymphocyte proliferation test without evidence of lung disease is
      diagnostic of BeS. BeS with evidence of a granulomatous inflammatory response in
      the lung is diagnostic of CBD. The determinants of progression from BeS to CBD
      are uncertain, but higher exposures and the presence of a genetic variant in the
      HLA-DP beta chain appear to increase the risk. Periodic evaluation of affected
      individuals can detect disease progression (from BeS to CBD, or from mild CBD to
      more severe CBD). Corticosteroid therapy is typically administered when a patient
      with CBD exhibits evidence of significant lung function abnormality or decline.
      CONCLUSIONS: Medical surveillance in workplaces that use beryllium-containing
      materials can identify individuals with BeS and at-risk groups of workers, which
      can help prioritize efforts to reduce inhalational and dermal exposures.

PMID- 25398120
TI  - Cerebral air embolism. A case of disseminated Klebsiella pneumoniae infection.

PMID- 25398121
TI  - Sarcoid-like reaction in diffuse idiopathic pulmonary neuroendocrine cell
      hyperplasia.

PMID- 25398122
TI  - Lung cancer prevention.
AB  - Lung cancer is a common form of cancer.There are things you can do to lower your
      risk of lung cancer. Stop smoking tobacco. Ask your health care provider for help
      in quitting, including use of medicines to help with nicotine dependence. discuss
      with your healthcare provider,what you are taking or doing to decrease your risk
      for lung cancer

PMID- 25398123
TI  - Development of [(11)C]MFTC for PET imaging of fatty acid amide hydrolase in rat
      and monkey brains.
AB  - We developed 2-methylpyridin-3-yl-4-(5-(2-fluorophenyl)-4H-1,2,4-triazol-3
      yl)piperidine-1-[(11)C]carboxylate ([(11)C]MFTC) as a promising PET tracer for in
      vivo imaging of fatty acid amide hydrolase (FAAH) in rat and monkey brains.
      [(11)C]MFTC was synthesized by reacting 3-hydroxy-2-methylpyridine (2) with
      [(11)C]phosgene ([(11)C]COCl2), followed by reacting with 4-(5-(2-fluorophenyl)
      4H-1,2,4-triazol-3-yl)piperidine (3), with a 20 +/- 4.6% radiochemical yield
      (decay-corrected, n = 30) based on [(11)C]CO2 and 40 min synthesis time from the
      end of bombardment. A biodistribution study in mice showed high uptake of
      radioactivity in FAAH-rich organs, including the lung, liver, and kidneys.
      Positron emission tomography (PET) summation images of rat brains showed high
      radioactivity in the frontal cortex, cerebellum, and hippocampus, which was
      consistent with the regional distribution pattern of FAAH in rodent brain.
      Pretreatment with MFTC or FAAH-selective URB597 significantly reduced the uptake
      in the brain. PET imaging of monkey brain showed relatively high uptake in the
      whole brain, particularly in the occipital cortex, which was also inhibited by
      treatment with MFTC or URB597. More than 96% of the total radioactivity was
      irreversible in the brain homogenate of rats 5 min after the radiotracer
      injection. The specific in vivo FAAH binding indicates that [(11)C]MFTC is a
      promising PET tracer for visualizing FAAH in the brain. 

PMID- 25398124
TI  - Resistant Microbial Keratitis in South Nile Delta, Egypt: Influence of Regional
      Risk Factors.
AB  - PURPOSE: This study was conducted in an attempt to identify the regional,
      geographic, climatic, socioeconomic, and other risk factors for microbial
      keratitis in south Nile Delta, Egypt. METHODS: This is a prospective cross
      sectional study that was carried out on 340 eyes of 340 patients with microbial
      keratitis attending at the outpatient clinic of Ophthalmology Department of
      Menoufia University Hospital during a period of three years between March 2010
      and March 2013. RESULTS: Epidemiological factors, lines of management, and follow
      up results were recorded and statistically analyzed and there were regional
      variations in the prevalence, risk factors, and outcome in resistant corneal
      ulcers. CONCLUSION: Higher incidence of affections and complications has appeared
      in farmers, rural area residents, and illiterates which are considered the main
      predisposing factors for ulcer resistance. According to culture results,
      bacterial organisms (especially Staphylococcus aureus) were the main cause of
      resistant corneal ulcers.

PMID- 25398125
TI  - Poppers Maculopathy: Complete Restitution of Macular Changes in OCT after Drug
      Abstinence.
AB  - BACKGROUND: "Poppers" is a slang term for a group of alkyl nitrites that are used
      as recreational drugs. Their inhalative intoxication leads to muscle relaxation,
      analgesia, and euphoria. Maculopathy is a rare but serious side-effect.
      PATIENTS/METHODS: Clinical, imaging, and electrophysiological findings of seven
      patients with maculopathy after consumption of poppers were presented. RESULTS:
      All seven patients were male with a median age of 35 years (range 28-45 years),
      the median duration of periodical poppers use until the onset of symptoms was 9.8
      years (one day to 25 years). Five of seven patients were HIV-positive, one
      patient was negative, and the HIV-status of one patient was unknown. Median
      average of visual acuity at presentation was 20/30 in each eye. In all patients,
      optical coherence tomography (OCT) showed pathognomonic alterations of the outer
      foveal retina. One patient showed an almost complete restitution of the
      maculopathy six months after cessation of drug use and following the oral intake
      of Lutein. Imaging alterations returned to normal and visual acuity recovered
      from 20/50 and 20/30 (right and left eye, respectively) to 20/20 on both eyes.
      Follow up of two other cases showed no relevant functional decline or
      improvement. DISCUSSION: Toxic maculopathy due to the consumption of poppers is
      an important differential diagnosis in acute visual loss without clinico
      morphological correlate. Optical coherence tomography is the only reliable
      diagnostic tool in these cases. Complete recovery of visual function and macular
      morphology is rare, even after cessation of drug abuse. Oral lutein therapy may
      have a beneficial effect.

PMID- 25398126
TI  - Decision tree analysis of traditional risk factors of carotid atherosclerosis and
      a cutpoint-based prevention strategy.
AB  - BACKGROUND: Reducing the exposure to risk factors for the prevention of cardio
      cerebral vascular disease is a crucial issue. Few reports have described
      practical interventions for preventing cardiovascular disease in different
      genders and age groups, particularly detailed and specific cutpoint-based
      prevention strategies. METHODS: We collected the health examination data of 5822
      subjects between 20 and 80 years of age. The administration of medical
      questionnaires and physical examinations and the measurement of blood pressure,
      fasting plasma glucose (FPG) and blood lipids [total cholesterol (TC),
      triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), and low density
      lipoprotein-cholesterol (LDL-C)] were performed by physicians. Carotid ultrasound
      was performed to examine the carotid intima-media thickness (CIMT), which was
      defined as carotid atherosclerosis when CIMT >=0.9 mm. Decision tree analysis was
      used to screen for the most important risk factors for carotid atherosclerosis
      and to identify the relevant cutpoints. RESULTS: In the study population, the
      incidence of carotid atherosclerosis was 12.20% (men: 14.10%, women: 9.20%). The
      statistical analysis showed significant differences in carotid atherosclerosis
      incidence between different genders (P<0.0001) and age groups (P<0.001). The
      decision tree analysis showed that in men, the most important traditional risk
      factors for carotid atherosclerosis were TC (cutpoint [CP]: 6.31 mmol/L) between
      the ages of 20-40 and FPG (CP: 5.79 mmol/L) between the ages of 41-59. By
      comparison, LDL-C (CP: 4.27 mmol/L) became the major risk factor when FPG <=5.79
      mmol/L. FPG (CP: 5.52 mmol/L) and TG (CP: 1.51 mmol/L) were the most important
      traditional risk factors for women between 20-40 and 41-59 years of age,
      respectively. CONCLUSION: Traditional risk factors and relevant cutpoints were
      not identical in different genders and age groups. A specific gender and age
      group-based cutpoint strategy might contribute to preventing cardiovascular
      disease.

PMID- 25398127
TI  - Evolution of mesh fixation for hernia repair.
AB  - Hernia repair remains one of the most common surgical procedures performed around
      the world. Over the past several decades, in response to various mesh-related
      complications and coinciding with the influx of laparoscopy into the field of
      general surgery, numerous advancements have been made in regards to the
      technology of mesh products being used in hernia repair today. Along these same
      lines, devices used for mesh fixation have evolved at a similar pace. The goal of
      this chapter is to review the various materials and methods of mesh fixation
      being utilized in both ventral and inguinal hernia repair today. 

PMID- 25398128
TI  - Persistent and compartmentalised disruption of dendritic cell subpopulations in
      the lung following influenza A virus infection.
AB  - Immunological homeostasis in the respiratory tract is thought to require balanced
      interactions between networks of dendritic cell (DC) subsets in lung
      microenvironments in order to regulate tolerance or immunity to inhaled antigens
      and pathogens. Influenza A virus (IAV) poses a serious threat of long-term
      disruption to this balance through its potent pro-inflammatory activities. In
      this study, we have used a BALB/c mouse model of A/PR8/34 H1N1 Influenza Type A
      Virus infection to examine the effects of IAV on respiratory tissue DC subsets
      during the recovery phase following clearance of the virus. In adult mice, we
      found differences in the kinetics and activation states of DC residing in the
      airway mucosa (AMDC) compared to those in the parenchymal lung (PLDC)
      compartments. A significant depletion in the percentage of AMDC was observed at
      day 4 post-infection that was associated with a change in steady-state CD11b+ and
      CD11b- AMDC subset frequencies and significantly elevated CD40 and CD80
      expression and that returned to baseline by day 14 post-infection. In contrast,
      percentages and total numbers of PLDC were significantly elevated at day 14 and
      remained so until day 21 post-infection. Accompanying this was a change in
      CD11b+and CD11b- PLDC subset frequencies and significant increase in CD40 and
      CD80 expression at these time points. Furthermore, mice infected with IAV at 4
      weeks of age showed a significant increase in total numbers of PLDC, and
      increased CD40 expression on both AMDC and PLDC, when analysed as adults 35 days
      later. These data suggest that the rate of recovery of DC populations following
      IAV infection differs in the mucosal and parenchymal compartments of the lung and
      that DC populations can remain disrupted and activated for a prolonged period
      following viral clearance, into adulthood if infection occurred early in life. 

PMID- 25398129
TI  - Multidisciplinary predialysis education reduced the inpatient and total medical
      costs of the first 6 months of dialysis in incident hemodialysis patients.
AB  - BACKGROUND: The multidisciplinary pre-dialysis education (MPE) retards renal
      progression, reduce incidence of dialysis and mortality of CKD patients. However,
      the financial benefit of this intervention on patients starting hemodialysis has
      not yet been evaluated in prospective and randomized trial. METHODS: We studied
      the medical expenditure and utilization incurred in the first 6 months of
      dialysis initiation in 425 incident hemodialysis patients who were randomized
      into MPE and non-MPE groups before reaching end-stage renal disease. The content
      of the MPE was standardized in accordance with the National Kidney Foundation
      Dialysis Outcomes Quality Initiative guidelines. RESULTS: The mean age of study
      patients was 63.8+/-13.2 years, and 221 (49.7%) of them were men. The mean serum
      creatinine level and estimated glomerular filtration rate was 6.1+/-4.0 mg/dL and
      7.6+/-2.9 mL?min(-1)?1.73 m(-2), respectively, at dialysis initiation. MPE
      patients tended to have lower total medical cost in the first 6 months after
      hemodialysis initiation (9147.6+/-0.1 USD/patient vs. 11190.6+/-0.1 USD/patient,
      p = 0.003), fewer in numbers [0 (1) vs. 1 (2), p<0.001] and length of
      hospitalization [0 (15) vs. 8 (27) days, p<0.001], and also lower inpatient cost
      [0 (2617.4) vs. 1559,4 (5019.6) USD/patient, p<0.001] than non-MPE patients,
      principally owing to reduced cardiovascular hospitalization and vascular access
      related surgeries. The decreased inpatient and total medical cost associated with
      MPE were independent of patients' demographic characteristics, concomitant
      disease, baseline biochemistry and use of double-lumen catheter at initiation of
      hemodialysis. CONCLUSIONS: Participation of multidisciplinary education in pre
      dialysis period was independently associated with reduction in the inpatient and
      total medical expenditures of the first 6 months post-dialysis owing to decreased
      inpatient service utilization secondary to cardiovascular causes and vascular
      access-related surgeries. TRIAL REGISTRATION: ClinicalTrials.gov NCT00644046.

PMID- 25398132
TI  - Chemical vapor deposition of high quality graphene films from carbon dioxide
      atmospheres.
AB  - The realization of graphene-based, next-generation electronic applications
      essentially depends on a reproducible, large-scale production of graphene films
      via chemical vapor deposition (CVD). We demonstrate how key challenges such as
      uniformity and homogeneity of the copper metal substrate as well as the growth
      chemistry can be improved by the use of carbon dioxide and carbon dioxide
      enriched gas atmospheres. Our approach enables graphene film production protocols
      free of elemental hydrogen and provides graphene layers of superior quality
      compared to samples produced by conventional hydrogen/methane based CVD
      processes. The substrates and resulting graphene films were characterized by
      scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX)
      and Raman microscopy, sheet resistance and transport measurements. The superior
      quality of the as-grown graphene films on copper is indicated by Raman maps
      revealing average G band widths as low as 18 +/- 8 cm(-1) at 514.5 nm excitation.
      In addition, high charge carrier mobilities of up to 1975 cm(2)/(V s) were
      observed for electrons in transferred films obtained from a carbon dioxide based
      growth protocol. The enhanced graphene film quality can be explained by the mild
      oxidation properties of carbon dioxide, which at high temperatures enables an
      uniform conditioning of the substrates by an efficient removal of pre-existing
      and emerging carbon impurities and a continuous suppression and in situ etching
      of carbon of lesser quality being co-deposited during the CVD growth. 

PMID- 25398130
TI  - S. mansoni bolsters anti-viral immunity in the murine respiratory tract.
AB  - The human intestinal parasite Schistosoma mansoni causes a chronic disease,
      schistosomiasis or bilharzia. According to the current literature, the parasite
      induces vigorous immune responses that are controlled by Th2 helper cells at the
      expense of Th1 helper cells. The latter cell type is, however, indispensable for
      anti-viral immune responses. Remarkably, there is no reliable literature among
      230 million patients worldwide describing defective anti-viral immune responses
      in the upper respiratory tract, for instance against influenza A virus or against
      respiratory syncitial virus (RSV). We therefore re-examined the immune response
      to a human isolate of S. mansoni and challenged mice in the chronic phase of
      schistosomiasis with influenza A virus, or with pneumonia virus of mice (PVM), a
      mouse virus to model RSV infections. We found that mice with chronic
      schistosomiasis had significant, systemic immune responses induced by Th1, Th2,
      and Th17 helper cells. High serum levels of TNF-alpha, IFN-gamma, IL-5, IL-13, IL
      2, IL-17, and GM-CSF were found after mating and oviposition. The lungs of
      diseased mice showed low-grade inflammation, with goblet cell hyperplasia and
      excessive mucus secretion, which was alleviated by treatment with an anti-TNF
      alpha agent (Etanercept). Mice with chronic schistosomiasis were to a relative,
      but significant extent protected from a secondary viral respiratory challenge.
      The protection correlated with the onset of oviposition and TNF-alpha-mediated
      goblet cell hyperplasia and mucus secretion, suggesting that these mechanisms are
      involved in enhanced immune protection to respiratory viruses during chronic
      murine schistosomiasis. Indeed, also in a model of allergic airway inflammation
      mice were protected from a viral respiratory challenge with PVM. 

PMID- 25398133
TI  - Gated Hall effect of nanoplate devices reveals surface-state-induced surface
      inversion in iron pyrite semiconductor.
AB  - Understanding semiconductor surface states is critical for their applications,
      but fully characterizing surface electrical properties is challenging. Such a
      challenge is especially crippling for semiconducting iron pyrite (FeS2), whose
      potential for solar energy conversion has been suggested to be held back by rich
      surface states. Here, by taking advantage of the high surface-to-bulk ratio in
      nanostructures and effective electrolyte gating, we develop a general method to
      fully characterize both the surface inversion and bulk electrical transport
      properties for the first time through electrolyte-gated Hall measurements of
      pyrite nanoplate devices. Our study shows that pyrite is n-type in the bulk and p
      type near the surface due to strong inversion and yields the concentrations and
      mobilities of both bulk electrons and surface holes. Further, solutions of the
      Poisson equation reveal a high-density of surface holes accumulated in a 1.3 nm
      thick strong inversion layer and an upward band bending of 0.9-1.0 eV. This work
      presents a general methodology for using transport measurements of nanostructures
      to study both bulk and surface transport properties of semiconductors. It also
      suggests that high-density of surface states are present on surface of pyrite,
      which partially explains the universal p-type conductivity and lack of
      photovoltage in polycrystalline pyrite. 

PMID- 25398131
TI  - CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial
      mesenchymal transition via PI3K/AKT signaling pathway.
AB  - Overexpressed CEACAM6 in tumor tissues plays important roles in invasion,
      metastasis and anoikis resistance in a variety of human cancers. We recently
      reported that CEACAM6 expression is upregulated in Gastric cancer (GC) tissues
      and promoted GC metastasis. Here, we report that CEACAM6 promotes peritoneal
      metastases in vivo and is negatively correlated with E-cadherin expression in GC
      tissues. Overexpressed CEACAM6 induced epithelial-mesenchymal transition (EMT) in
      GC, as measured by increases in the EMT markers N-cadherin, Vimentin and Slug
      while E-cadherin expression was decreased in CEACAM6-overexpressing GC cells;
      opposing results were observed in CEACAM6-silenced cells. Furthermore, E-cadherin
      expression was negatively correlated with depth of tumor invasion, lymph node
      metastasis and TNM stage in GC tissues. Additionally, CEACAM6 elevated matrix
      metalloproteinase-9 (MMP-9) activity in GC, and anti-MMP-9 antibody could reverse
      the increasing invasion and migration induced by CEACAM6. CEACAM6 also increased
      the levels of phosphorylated AKT, which is involved in the progression of a
      variety of human tumors. We further observed that LY294002, a PI3K inhibitor,
      could reverse CEACAM6-induced EMT via mesenchymal-epithelial transition. These
      findings suggest that CEACAM6 enhances invasion and metastasis in GC by promoting
      EMT via the PI3K/AKT signaling pathway. 

PMID- 25398134
TI  - Towards an optimization of stimulus parameters for brain-computer interfaces
      based on steady state visual evoked potentials.
AB  - Efforts to construct an effective brain-computer interface (BCI) system based on
      Steady State Visual Evoked Potentials (SSVEP) commonly focus on sophisticated
      mathematical methods for data analysis. The role of different stimulus features
      in evoking strong SSVEP is less often considered and the knowledge on the optimal
      stimulus properties is still fragmentary. The goal of this study was to provide
      insight into the influence of stimulus characteristics on the magnitude of SSVEP
      response. Five stimuli parameters were tested: size, distance, colour, shape, and
      presence of a fixation point in the middle of each flickering field. The stimuli
      were presented on four squares on LCD screen, with each square highlighted by
      LEDs flickering with different frequencies. Brighter colours and larger
      dimensions of flickering fields resulted in a significantly stronger SSVEP
      response. The distance between stimulation fields and the presence or absence of
      the fixation point had no significant effect on the response. Contrary to a
      popular belief, these results suggest that absence of the fixation point does not
      reduce the magnitude of SSVEP response. However, some parameters of the stimuli
      such as colour and the size of the flickering field play an important role in
      evoking SSVEP response, which indicates that stimuli rendering is an important
      factor in building effective SSVEP based BCI systems. 

PMID- 25398135
TI  - Nitrogen limitation and slow drying induce desiccation tolerance in conjugating
      green algae (Zygnematophyceae, Streptophyta) from polar habitats.
AB  - BACKGROUND: Filamentous Zygnematophyceae are typical components of algal mats in
      the polar hydro-terrestrial environment. Under field conditions, they form
      senescent vegetative cells, designated as pre-akinetes, which are tolerant to
      desiccation and osmotic stress. KEY FINDINGS: Pre-akinete formation and
      desiccation tolerance was investigated experimentally under monitored laboratory
      conditions in four strains of Arctic and Antarctic isolates with vegetative
      Zygnema sp. morphology. Phylogenetic analyses of rbcL sequences revealed one
      Arctic strain as genus Zygnemopsis, phylogenetically distant from the closely
      related Zygnema strains. Algae were cultivated in liquid or on solidified medium
      (9 weeks), supplemented with or lacking nitrogen. Nitrogen-free cultures (liquid
      as well as solidified) consisted of well-developed pre-akinetes after this
      period. Desiccation experiments were performed at three different drying rates
      (rapid: 10% relative humidity, slow: 86% rh and very slow); viability, effective
      quantum yield of PS II, visual and ultrastructural changes were monitored.
      Recovery and viability of pre-akinetes were clearly dependent on the drying rate:
      slower desiccation led to higher levels of survival. Pre-akinetes survived rapid
      drying after acclimation by very slow desiccation. CONCLUSIONS: The formation of
      pre-akinetes in polar Zygnema spp. and Zygnemopsis sp. is induced by nitrogen
      limitation. Pre-akinetes, modified vegetative cells, rather than specialized
      stages of the life cycle, can be hardened by mild desiccation stress to survive
      rapid drying. Naturally hardened pre-akinetes play a key role in stress tolerance
      and dispersal under the extreme conditions of polar regions, where sexual
      reproduction and production of dormant stages is largely suppressed.

PMID- 25398136
TI  - Chronic maternal vitamin B12 restriction induced changes in body composition &
      glucose metabolism in the Wistar rat offspring are partly correctable by
      rehabilitation.
AB  - Maternal under-nutrition increases the risk of developing metabolic diseases. We
      studied the effects of chronic maternal dietary vitamin B12 restriction on lean
      body mass (LBM), fat free mass (FFM), muscle function, glucose tolerance and
      metabolism in Wistar rat offspring. Prevention/reversibility of changes by
      rehabilitating restricted mothers from conception or parturition and their
      offspring from weaning was assessed. Female weaning Wistar rats (n = 30) were fed
      ad libitum for 12 weeks, a control diet (n = 6) or the same with 40% restriction
      of vitamin B12 (B12R) (n = 24); after confirming deficiency, were mated with
      control males. Six each of pregnant B12R dams were rehabilitated from conception
      and parturition and their offspring weaned to control diet. While offspring of
      six B12R dams were weaned to control diet, those of the remaining six B12R dams
      continued on B12R diet. Biochemical parameters and body composition were
      determined in dams before mating and in male offspring at 3, 6, 9 and 12 months
      of their age. Dietary vitamin B12 restriction increased body weight but decreased
      LBM% and FFM% but not the percent of tissue associated fat (TAF%) in dams.
      Maternal B12R decreased LBM% and FFM% in the male offspring, but their TAF%,
      basal and insulin stimulated glucose uptake by diaphragm were unaltered. At 12
      months age, B12R offspring had higher (than controls) fasting plasma glucose,
      insulin, HOMA-IR and impaired glucose tolerance. Their hepatic gluconeogenic
      enzyme activities were increased. B12R offspring had increased oxidative stress
      and decreased antioxidant status. Changes in body composition, glucose metabolism
      and stress were reversed by rehabilitating B12R dams from conception, whereas
      rehabilitation from parturition and weaning corrected them partially,
      highlighting the importance of vitamin B12 during pregnancy and lactation on
      growth, muscle development, glucose tolerance and metabolism in the offspring. 

PMID- 25398138
TI  - Cooperative binding of aflatoxin B1 by cytochrome P450 3A4: a computational
      study.
AB  - Aflatoxin B1 (AFB1)-the most potent natural carcinogen known to men-is
      metabolized by cytochrome P450 3A4 (CYP3A4), either to the genotoxic AFB1 exo-8,9
      epoxide or to the detoxified 3alpha-hydroxy AFB1. The activation of the
      procarcinogen proceeds in a highly cooperative fashion, which differs from common
      allosteric regulation in the sense that it can be attributed to simultaneous
      occupancy of a single large and malleable active site by multiple ligand
      molecules. Unfortunately, unlike in the case of ketoconazole, there is currently
      no experimental structure available for the doubly ligated CYP3A4-AFB1 complex.
      Therefore, we employed a sequential molecular docking protocol to create various
      possible doubly ligated complexes and subsequently performed molecular dynamics
      simulations and free-energy calculations to check for their consistency with the
      available experimental data on regio- and stereoselectivity of both AFB1
      oxidations as well as with available kinetic data. Only the system in which the
      first AFB1 molecule was bound in a face-on C8-C9 epoxidation mode and the second
      AFB1 molecule was bound in a side-on 3alpha-hydroxylation mode-a result of an
      unconstrained molecular docking protocol-has successfully fulfilled all the
      imposed criteria and is therefore proposed as the most likely structure of the
      doubly ligated complex of CYP3A4 with AFB1. The empirical Linear Interaction
      Energy method revealed that shape complementarity through nonpolar dispersion
      interactions between the two bound AFB1 molecules is the main source of the
      experimentally observed positive homotropic cooperativity. The reported study
      represents a nice example of how state-of-the-art molecular modeling techniques
      can be used to study complicated macromolecular complexes, whose structures have
      not yet been experimentally determined, and to validate these against the
      available experimental data. The proposed structure will facilitate future
      studies on the rational design of successful AFB1 modulators or on human
      subpopulations characterized by specific CYP3A4 polymorphisms that are especially
      sensitive to AFB1.

PMID- 25398137
TI  - Intranasal administration of a therapeutic HIV vaccine (Vacc-4x) induces dose
      dependent systemic and mucosal immune responses in a randomized controlled trial.
AB  - BACKGROUND: Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to
      reduce viral load set-points after intradermal administration. In this randomized
      controlled pilot study we investigate intranasal administration of Vacc-4x with
      Endocine as adjuvant. METHODS: Safety and immunogenicity were tested in patients
      on effective ART. They were randomized to low, medium or high dose Vacc-4x or
      adjuvant alone, administered four times at weekly intervals with no booster. Vacc
      4x-specific T cell responses were measured in vitro by proliferation and in vivo
      by a single DTH skin test at the end of study. Nasal and rectal mucosal
      secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune
      regulation induced by Vacc-4x was assessed by functional blockade of the
      regulatory cytokines IL-10 and TGF-beta. RESULTS: Vacc-4x proliferative T cell
      responses increased only among the vaccinated (p <= 0.031). The low dose group
      showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037) and
      developed larger DTH (p = 0.005) than the adjuvant group. Rectal (distal) Vacc-4x
      IgA and IgG antibodies also increased (p = 0.043) in this group. In contrast, the
      high dose generated higher nasal (local) Vacc-4x IgA (p = 0.028) and serum IgG (p
      = 0.030) antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x
      CD4+T cell responses were associated with low proliferation (r = -0.82, p <
      0.001) and high regulation (r = 0.61, p = 0.010) at baseline. CONCLUSION:
      Intranasal administration of Vacc-4x with Endocine was safe and induced dose
      dependent vaccine-specific T cell responses and both mucosal and systemic humoral
      responses. The clinical significance of dose, immune regulation and mucosal
      immunity warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01473810.

PMID- 25398139
TI  - Fine mapping and candidate gene search of quantitative trait loci for growth and
      obesity using mouse intersubspecific subcongenic intercrosses and exome
      sequencing.
AB  - Although growth and body composition traits are quantitative traits of medical
      and agricultural importance, the genetic and molecular basis of those traits
      remains elusive. Our previous genome-wide quantitative trait locus (QTL) analyses
      in an intersubspecific backcross population between C57BL/6JJcl (B6) and wild Mus
      musculus castaneus mice revealed a major growth QTL (named Pbwg1) on a proximal
      region of mouse chromosome 2. Using the B6.Cg-Pbwg1 intersubspecific congenic
      strain created, we revealed 12 closely linked QTLs for body weight and body
      composition traits on an approximately 44.1-Mb wild-derived congenic region. In
      this study, we narrowed down genomic regions harboring three (Pbwg1.12, Pbwg1.3
      and Pbwg1.5) of the 12 linked QTLs and searched for possible candidate genes for
      the QTLs. By phenotypic analyses of F2 intercross populations between B6 and each
      of four B6.Cg-Pbwg1 subcongenic strains with overlapping and non-overlapping
      introgressed regions, we physically defined Pbwg1.12 affecting body weight to a
      3.8-Mb interval (61.5-65.3 Mb) on chromosome 2. We fine-mapped Pbwg1.3 for body
      length to an 8.0-Mb interval (57.3-65.3) and Pbwg1.5 for abdominal white fat
      weight to a 2.1-Mb interval (59.4-61.5). The wild-derived allele at Pbwg1.12 and
      Pbwg1.3 uniquely increased body weight and length despite the fact that the wild
      mouse has a smaller body size than that of B6, whereas it decreased fat weight at
      Pbwg1.5. Exome sequencing and candidate gene prioritization suggested that Gcg
      and Grb14 are putative candidate genes for Pbwg1.12 and that Ly75 and Itgb6 are
      putative candidate genes for Pbwg1.5. These genes had nonsynonymous SNPs, but the
      SNPs were predicted to be not harmful to protein functions. These results provide
      information helpful to identify wild-derived quantitative trait genes causing
      enhanced growth and resistance to obesity. 

PMID- 25398140
TI  - Direct detection and differentiation of pathogenic Leptospira species using a
      multi-gene targeted real time PCR approach.
AB  - Leptospirosis is a growing public and veterinary health concern caused by
      pathogenic species of Leptospira. Rapid and reliable laboratory tests for the
      direct detection of leptospiral infections in animals are in high demand not only
      to improve diagnosis but also for understanding the epidemiology of the disease.
      In this work we describe a novel and simple TaqMan-based multi-gene targeted real
      time PCR approach able to detect and differentiate Leptospira interrogans, L.
      kirschneri, L. borgpeteresenii and L. noguchii, which constitute the veterinary
      most relevant pathogenic species of Leptospira. The method uses sets of species
      specific probes, and respective flanking primers, designed from ompL1 and secY
      gene sequences. To monitor the presence of inhibitors, a duplex amplification
      assay targeting both the mammal beta-actin and the leptospiral lipL32 genes was
      implemented. The analytical sensitivity of all primer and probe sets was
      estimated to be <10 genome equivalents (GE) in the reaction mixture. Application
      of the amplification reactions on genomic DNA from a variety of pathogenic and
      non-pathogenic Leptospira strains and other non-related bacteria revealed a 100%
      analytical specificity. Additionally, pathogenic leptospires were successfully
      detected in five out of 29 tissue samples from animals (Mus spp., Rattus spp.,
      Dolichotis patagonum and Sus domesticus). Two samples were infected with L.
      borgpetersenii, two with L. interrogans and one with L. kirschneri. The
      possibility to detect and identify these pathogenic agents to the species level
      in domestic and wildlife animals reinforces the diagnostic information and will
      enhance our understanding of the epidemiology of leptopirosis. 

PMID- 25398141
TI  - Enhanced slow-wave EEG activity and thermoregulatory impairment following the
      inhibition of the lateral hypothalamus in the rat.
AB  - Neurons within the lateral hypothalamus (LH) are thought to be able to evoke
      behavioural responses that are coordinated with an adequate level of autonomic
      activity. Recently, the acute pharmacological inhibition of LH has been shown to
      depress wakefulness and promote NREM sleep, while suppressing REM sleep. These
      effects have been suggested to be the consequence of the inhibition of specific
      neuronal populations within the LH, i.e. the orexin and the MCH neurons,
      respectively. However, the interpretation of these results is limited by the lack
      of quantitative analysis of the electroencephalographic (EEG) activity that is
      critical for the assessment of NREM sleep quality and the presence of aborted
      NREM-to-REM sleep transitions. Furthermore, the lack of evaluation of the
      autonomic and thermoregulatory effects of the treatment does not exclude the
      possibility that the wake-sleep changes are merely the consequence of the
      autonomic, in particular thermoregulatory, changes that may follow the inhibition
      of LH neurons. In the present study, the EEG and autonomic/thermoregulatory
      effects of a prolonged LH inhibition provoked by the repeated local delivery of
      the GABAA agonist muscimol were studied in rats kept at thermoneutral (24 degrees
      C) and at a low (10 degrees C) ambient temperature (Ta), a condition which is
      known to depress sleep occurrence. Here we show that: 1) at both Tas, LH
      inhibition promoted a peculiar and sustained bout of NREM sleep characterized by
      an enhancement of slow-wave activity with no NREM-to-REM sleep transitions; 2) LH
      inhibition caused a marked transitory decrease in brain temperature at Ta 10
      degrees C, but not at Ta 24 degrees C, suggesting that sleep changes induced by
      LH inhibition at thermoneutrality are not caused by a thermoregulatory
      impairment. These changes are far different from those observed after the short
      term selective inhibition of either orexin or MCH neurons, suggesting that other
      LH neurons are involved in sleep-wake modulation. 

PMID- 25398143
TI  - Combination HIV prevention among MSM in South Africa: results from agent-based
      modeling.
AB  - HIV prevention trials have demonstrated the effectiveness of a number of
      behavioral and biomedical interventions. HIV prevention packages are combinations
      of interventions and offer potential to significantly increase the effectiveness
      of any single intervention. Estimates of the effectiveness of prevention packages
      are important for guiding the development of prevention strategies and for
      characterizing effect sizes before embarking on large scale trials.
      Unfortunately, most research to date has focused on testing single interventions
      rather than HIV prevention packages. Here we report the results from agent-based
      modeling of the effectiveness of HIV prevention packages for men who have sex
      with men (MSM) in South Africa. We consider packages consisting of four
      components: antiretroviral therapy for HIV infected persons with CD4 count <350;
      PrEP for high risk uninfected persons; behavioral interventions to reduce rates
      of unprotected anal intercourse (UAI); and campaigns to increase HIV testing. We
      considered 163 HIV prevention packages corresponding to different intensity
      levels of the four components. We performed 2252 simulation runs of our agent
      based model to evaluate those packages. We found that a four component package
      consisting of a 15% reduction in the rate of UAI, 50% PrEP coverage of high risk
      uninfected persons, 50% reduction in persons who never test for HIV, and 50% ART
      coverage over and above persons already receiving ART at baseline, could prevent
      33.9% of infections over 5 years (95% confidence interval, 31.5, 36.3). The
      package components with the largest incremental prevention effects were UAI
      reduction and PrEP coverage. The impact of increased HIV testing was magnified in
      the presence of PrEP. We find that HIV prevention packages that include both
      behavioral and biomedical components can in combination prevent significant
      numbers of infections with levels of coverage, acceptance and adherence that are
      potentially achievable among MSM in South Africa. 

PMID- 25398145
TI  - [Amniotic fluid embolism - review].
AB  - Amniotic fluid embolism is a rare but mortal pregnancy complication.
      Presentations may vary from subtle clinical events to sudden cardiac arrest or
      death. Amniotic fluid embolism is one of the most common cause of maternal
      mortality in developed countries. Basic principle is amniotic fluid and its
      particles gaining access to maternal circulation. It is supposed, that these
      particles trigger immune-based mechanism. This results into wide spectrum of
      clinical symptoms, especially cardiovascular, respiratory and haematological.
      Treatment of these symptoms needs an acute interdisciplinary cooperation. AFE
      mortality is decreasing in recent times. It is mainly because of increase of
      quality of intensive care and inclusion of less severe episodes in perinatal
      pathology registries. KEYWORDS: amniotic fluid embolism, anaphylactic shock,
      sepsis.

PMID- 25398144
TI  - Simple, chemoselective, catalytic olefin isomerization.
AB  - Catalytic amounts of Co(Sal(tBu,tBu))Cl and organosilane irreversibly isomerize
      terminal alkenes by one position. The same catalysts effect cycloisomerization of
      dienes and retrocycloisomerization of strained rings. Strong Lewis bases like
      amines and imidazoles, and labile functionalities like epoxides, are tolerated. 

PMID- 25398146
TI  - [Prebioptic methods in the cervical cancer screening].
AB  - OBJECTIVE: To evaluate the agreement between Pap smears, colposcopic findings and
      definitive excisional specimen in patients with abnormal Pap smears. DESIGN:
      Retrospective study. SETTING: Center of outpatient gynecology and primary care,
      Brno; Department of Obstetrics and Gynecology, University Hospital, Olomouc;
      Department of Medical Biophysics, Palacky University, Olomouc.Subjects and
      methods of the study: This retrospective study assessed the correlation between
      colposcopy and histopathology of woman who had abnormal Pap smears. Colposcopic
      chart review included participants from 2008 to 2012 who attended colposcopic
      clinic, center of outpatient gynecology care, Brno. RESULTS: One thousand nine
      hundred and twenty five patients screened by cytology, submitted to colposcopy
      and subjected to cone biopsy were selected. Cytopathological results were
      compared with colposcopic findings and results obtained on the basis of
      histological analyses of cone biopsy specimen. Agreement of cytology and
      histopathological diagnosis was in 1199 patients (62.3%). Agreement of
      colposcopic diagnosis and cervical pathology was matched in 1492 (93.5%).
      Agreement of colposcopy and cytology was found in 1022 pacientek (64.1%). False
      negatives of cytology in high grade lesions were in 36.4%. CONCLUSION: Strength
      of agreement between colposcopic diagnosis and cervical pathology was found to be
      very good while for cytology high percentage of false negative results was seen.
      Expert colposcopists and high quality standard cytopathologic and bioptic
      laboratories are necessary for nationwide cervical screening programmes.
      KEYWORDS: cervical cancer, colposcopy, oncological cytology, histology, CIN, cone
      biopsy.

PMID- 25398147
TI  - The most valuable predictorsof endometrial receptivity.
AB  - OBJECTIVE: To investigate the predictive factors of insufficient endometrial
      quality. DESIGN: Review. SETTING: Department of Obstetrics and Gynecology,
      General Faculty Hospital Prague, 1st Faculty of Medicine, Charles University.
      RESULTS: This is the review on predictive factors of endometrial receptivity.
      There is a collected data on homeobox genes family, especially HOX 10 and HOX 11
      members, that ensure implantation process by means of their interaction with
      estrogen and progesterone receptors via stimulatory proteins in the luminal
      epithelium in different periods of luteal phase. Moreover, the article describes
      appropriate secretion of osteoponin, cadherin, selectin, apopoliprotein D, mucin
      and balanced macrophage activity in endometrial epithelium in the proliferative
      phase of the menstrual cycle provide optimal conditions for implantation.
      CONCLUSION: Endometrial genes expressions along with the intrauterine environment
      macrophages activity maintain the tiny mechanism of endometrial receptivity.

PMID- 25398148
TI  - [Prenatal growth curves of the Czech population].
AB  - OBJECTIVE: Determination of ultrasound biometric parameters of fetuses in the
      Czech population during pregnancy. METHODS: We retrospectively analyzed a data
      set of 20,566 pregnant women from the years 2008 to 2012 who met the following
      inclusion criteria: Caucasian ethnicity; measured biometric parameters biparietal
      diameter (BPD), head circumference (HC), abdominal circumference (AC), femur
      length (FL); body mass index (BMI) of the pregnant women < 35 kg/m2.We excluded
      pregnant women with multiple fibroids distorting the uterine cavity;
      pathologically developing fetuses; and pregnancies where we were not able to
      verify the correct dating. We did not carry out selection as to the method of
      getting pregnant. The pregnancy age was from 19+0 to 42+6 gestation weeks. As in
      all studies, the age of pregnancy refers to the completed gestation weeks (for
      instance 23+0 to 23+6 = 23rd gestation week). We then compared our newly derived
      growth curves with the curves currently used, for BPD, HC, AC, FL and EFW, in the
      3rd or 5th percentile, 50th percentile and 95th or 97th percentile (according to
      data obtained from reference studies). RESULTS: The study included 40,806
      observations. The number of observations exceeded 500 in all weeks except in the
      42nd week. The median age of the pregnant patients was 31.9 years (min 14.9, max
      52.54). In the studied group we found a lower degree of variability in all
      parameters. The biometric parameters had higher values for the gestation week
      than the reference parameters. The estimated weight of the fetuses in our group
      on the level of the 3rd percentile was significantly higher than the reference
      value. DISCUSSION: The study was based exclusively on sonographic measurements.
      Although we excluded from our group intrauterine pathologies that could affect
      the physiological growth of the fetus, we did not carry out an additional
      selection using information on the pathologies of fetuses obtained postnatally.
      However, as the study contains more than 40,000 measurements, we can assume that
      such additional selection would have had only a minimum effect on the resulting
      curve. A section of the fetuses that would have been considered eutrophic
      according to present reference studies could be considered hypotrophic or small
      for gestational age (SGA) according to our observations. CONCLUSION: We have
      obtained new prenatal ultrasound growth curves for the Czech population of
      healthy developing fetuses. In early gestation weeks, we have found statistically
      significant deviations from the reference studies. Fetuses in our study have
      significantly higher weight estimate and show a lower degree of variability
      compared to the reference studies. KEYWORDS: prenatal, ultrasound diagnosis,
      fetal biometry, percentile curves, biparietal diameter, head circumference,
      abdominal circumference, femur length, estimated fetal weight, Czech population.

PMID- 25398142
TI  - A simplified and versatile system for the simultaneous expression of multiple
      siRNAs in mammalian cells using Gibson DNA Assembly.
AB  - RNA interference (RNAi) denotes sequence-specific mRNA degradation induced by
      short interfering double-stranded RNA (siRNA) and has become a revolutionary tool
      for functional annotation of mammalian genes, as well as for development of novel
      therapeutics. The practical applications of RNAi are usually achieved by
      expressing short hairpin RNAs (shRNAs) or siRNAs in cells. However, a major
      technical challenge is to simultaneously express multiple siRNAs to silence one
      or more genes. We previously developed pSOS system, in which siRNA duplexes are
      made from oligo templates driven by opposing U6 and H1 promoters. While
      effective, it is not equipped to express multiple siRNAs in a single vector.
      Gibson DNA Assembly (GDA) is an in vitro recombination system that has the
      capacity to assemble multiple overlapping DNA molecules in a single isothermal
      step. Here, we developed a GDA-based pSOK assembly system for constructing single
      vectors that express multiple siRNA sites. The assembly fragments were generated
      by PCR amplifications from the U6-H1 template vector pB2B. GDA assembly
      specificity was conferred by the overlapping unique siRNA sequences of insert
      fragments. To prove the technical feasibility, we constructed pSOK vectors that
      contain four siRNA sites and three siRNA sites targeting human and mouse beta
      catenin, respectively. The assembly reactions were efficient, and candidate
      clones were readily identified by PCR screening. Multiple beta-catenin siRNAs
      effectively silenced endogenous beta-catenin expression, inhibited Wnt3A-induced
      beta-catenin/Tcf4 reporter activity and expression of Wnt/beta-catenin downstream
      genes. Silencing beta-catenin in mesenchymal stem cells inhibited Wnt3A-induced
      early osteogenic differentiation and significantly diminished synergistic
      osteogenic activity between BMP9 and Wnt3A in vitro and in vivo. These findings
      demonstrate that the GDA-based pSOK system has been proven simplistic, effective
      and versatile for simultaneous expression of multiple siRNAs. Thus, the reported
      pSOK system should be a valuable tool for gene function studies and development
      of novel therapeutics. 

PMID- 25398149
TI  - [Correlation between the incidence of PIK3CA mutations in breast cancer and
      histopathological characteristics of the tumor].
AB  - OBJECTIVE: To determine the presence of mutations in exon 9 (encoding the helical
      domain) and exon 20 (encoding the kinase domain) of phosphatidylinositol-4,5
      bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene in DNA obtained from
      paraffin embedded tissue from patients with carcinoma of the mammary gland and to
      correlate results with clinicopathological characteristics of cancer. DESIGN:
      Prospective clinical study. SETTING: Department of Molecular Biology, Department
      of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Commenius
      University, Martin, Slovak Republic. METHODS: In set of 95 tissue samples from
      patients with breast cancer, mutations in exon 9 and 20 were analysed by
      sequencing. We also observed the associations between mutations and
      histopathological characteristics of tumor. RESULTS: Overall, mutations were
      present in 25.3% (24/95) of PIK3CA gene, of this 14.7% (14/95) of mutations were
      located in exon 9 and 10.5% (10/95) of mutations were in exon 20. We detected
      three "hotspot" mutations, two were located in exon 9 (E542K, E545K) and the
      third mutation was found in exon 20 (H1047R). Mutations in exon 9 showed
      significant correlation with lower grade(p = 0.0074) and pN status without
      metastases(p = 0.0415). Mutations in exon 20 were associated with higher age of
      patient (p = 0.0249). The E545K mutation correlated with lower grade (p = 0.0013)
      and pN status (p = 0.0232) particularly; the H1047R mutation was significantly
      more frequent in lobular type of breast cancer (p = 0.0354). CONCLUSION: The PI3K
      signaling pathway plays a critical oncogenic role in the development of human
      breast cancer and the prevalence of its deregulation advocates its potential as a
      feasible therapeutic target. In our study we demonstrate a significant
      correlation between the presence of PIK3CA mutations and some clinicopathological
      characteristics of tumour. We have shown that the mutations in exon 9 of PIK3CA
      were associated with favourable prognostic factors. KEYWORDS: "hotspot" mutation,
      PIK3CA, PI3K pathway, breast cancer.

PMID- 25398150
TI  - [Characteristics of sexual maturation in girls in Bratislava region].
AB  - OBJECTIVE: Evaluation of puberty onset and menarche in girls in Bratislava region
      in the years 2006-2007 and 2011-2013. DESIGN: Regional retrospective
      epidemiological study. SETTING: 1st Department of Gynaecology and Obstetrics,
      School of Medicine, Comenius University and University Hospital Bratislava,
      Slovenske republika. METHODS: A study in two periods was performed. The first was
      in the years 2006-2007 and the second in 2011-2013. Together 217 girls aged 7-16
      were enrolled. Secondary sexual characteristics according to Tanner were
      evaluated. Ultrasound examination of the uterus and ovaries was performed. The
      results were statistically evaluated by software Statistical Package for Social
      Sciences (SPSS) by age, and compared to results of Slovak study held in the years
      1976-1980. RESULTS: The mean age of menarche onset of girls in the group was
      12.37. Pubarche and adrenarche onset were at 10.7 and 11.7 year respectively.
      Thelarche onset was at 10.9 year. Development of secondary sexual characteristics
      significantly correlated with ultrasound parameters of internal genitalia and
      with age of menarche. Average ultrasound parameters increases with age to 15
      years. Significant changes were for average anteroposterior uterine size in 11
      and 13 years old girls, for proportion corpus/cervix of the uterus in 9 and 11
      years old girls and for average ovarian volume in 9, 11, 14 and 15 years old
      girls. CONCLUSION: The results from our study comparing to those from study held
      in 1976-1980 shows continuous secular trend in Bratislava region. KEYWORDS: age
      of menarche, secular trend, puberty, secondary sexual characteristics.

PMID- 25398151
TI  - Effect of six antiretroviral drugs (delavirdine, stavudine, lamivudine,
      nelfinavir, amprenavir and lopinavir/ritonavir in association) on albino pregnant
      rats (Rattus norvegicus Albinus, Rodentia, Mammalia): biological assay.
AB  - OBJECTIVE: To compare the chronic effects of antiretrovirals (lamivudine,
      stavudine, delavirdine, nelfinavir, amprenavir and an association of
      lopinavir/ritonavir) on albino pregnant rats. DESIGN: Review. SETTING: Department
      of Obstetrics, Federal University of Sao Paulo (UNIFESP), Sao Paulo, SP, Brazil.
      METHODS: This was a comparative retrospective study formed by 18 groups of 10
      pregnant rats each, which were nearly three months of age and weighed 200 g. All
      of them were medicated every day using a stomach probe, while the control group
      was given 1 mL of distilled water. The study groups received lamivudine (at 5, 15
      and 45 mg/kg/day); stavudine (at 1, 3 and 9 mg/kg/day); nelfinavir (at 40, 120
      and 360 mg/kg/day); amprenavir (at 46, 138 and 414 mg/kg/day);
      lopinavir/ritonavir (at 12.8/3.2, 38.4/9.6 and 115/28.8 mg/kg/day) and
      delavirdine (at 20 and 60 mg/kg/day). These represented 1, 3 and 9 times the
      human therapeutic dose, except for the last drug, for which the 9-times dose was
      not used. Maternal, litter and placental weights, implantation and reabsorption
      numbers, major external fetal malformations and fetal and maternal deaths were
      evaluated. The Kruskal-Wallis test was used to compare quantitative variables and
      the chi-square test was used to compare qualitative variables. RESULTS: At all
      three doses, stavudine increased the maternal weight (p=0.001), while lamivudine
      at 3- and 9-times doses reduced it (p<0.001). Amprenavir at all of the doses, and
      lopinavir/ritonavir at 3- and 9-times doses, caused higher rates of maternal
      death (p<0.001). Regarding the fetuses, none of the antiretroviral drugs studied
      were harmful with regard to implantation, reabsorption, teratogenity and
      mortality (p>0.05). Stavudine at all doses reduced the litter weights (p<0.001);
      however, lamivudine at the usual and 3-times doses, delavirdine at 3-times dose,
      and amprenavir at 3-times dose increased the litter weight (p<0.001). CONCLUSION:
      In the maternal compartment, we observed lethal toxicity in the pregnant rats
      that received amprenavir and ritonavir/lopinavir; and maternal weight change with
      lamivudine and stavudine. In the fetal compartment, adverse effects were observed
      in relation to litter weight from stavudine, lamivudine, delavirdine and
      amprenavir.

PMID- 25398152
TI  - Tuberculosis in pregnancy:a challenging differential diagnosisfor inflammatory
      bowel disease.
AB  - OBJECTIVE: To describe a case of tuberculosis with intestinal variant in a
      pregnant woman in the 17th week of pregnancy. DESIGN: Case report. SETTING:
      Department of Obstetrics, Federal University of Sao Paulo (UNIFESP), Sao Paulo
      SP, Brazil. CONCLUSION: Tuberculosis is a public health problem that concerns
      many countries in the world. It was declareda public emergency by the World
      Health Organization in 2005. Its presence during pregnancy brings maternal risk
      and fetal impairment if not treated quickly and properly. The intestinal variant
      is not the most common form of the disease and may be confused with inflammatory
      bowel diseases, especially Crohns disease. Knowledge of the specific
      characteristics, combined with a detailed medical history and appropriate
      diagnostic methods can make all the difference in gestational prognosis. We
      report the case of a pregnant woman who wrongly underwent treatment for
      inflammatory bowel disease at another service. After admission to our university
      hospital, fruitful diagnostic clarification was achieved and the patient was
      diagnosed and treated for tuberculosis. We describe the details of the
      investigation and, in particular, review the main characteristics in the
      literature for differentiating the two diseases.

PMID- 25398153
TI  - [Pregnancy and delivery in patients with an implanted shunt for hydrocephalus].
AB  - Hydrocephalus is a disorder of abnormal accumulation of cerebrospinal fluid in
      the intracranial space, usually in the cerebral ventricles. The number of
      patients reaching reproductive age and intending to become pregnant has increased
      in recent years because of treatment advances. An implanted shunt is usually
      introduced into the abdominal cavity (ventriculoperitoneal shunt). Numerous
      changes occur during pregnancy, mainly increased accumulation of water, increased
      intracranial cerebrospinal fluid volume and increased intra-abdominal pressure as
      a result of the growing uterus. These changes contribute to increased incidence
      of complications during pregnancy and childbirth. Therefore, it is necessary to
      make a preconception exam and specify pregnancy management, a suitable method of
      childbirth and dealing with potential complications. Multidisciplinary care is
      mandatory with the dominant cooperation of obstetricians and neurosurgeons who
      should be also available during the delivery when needed. Possible shunt
      malfunction is necessary to diagnose properly and in time and solve it
      individually, taking into account the overall and neurological status of the
      patient and gestational age. The presence of a shunt does not affect pregnancy
      and vaginal delivery is considered by most authors as the first option. Primary
      cesarean section is preffered in patients with obstructive hydrocephalus or rapid
      deterioration in the case of shunt malfunction. Epidural anesthesia or general,
      eventually spinal anesthesia are recommended. KEYWORDS: hydrocephalus, shunt,
      ventriculoperitoneal shunt, ventriculoatrial shunt, endoscopy, endoscopic third
      ventriculostomy, pregnancy.

PMID- 25398154
TI  - [Dysplasia and cervical cancer: current diagnostic possibilities].
AB  - OBJECTIVE: To review current methods in the diagnosis of dysplasia and cervical
      cancer. DESIGN: Review article. SETTING: Reprofit International Ltd., Brno;
      Department of Gynecology and Obstetrics, University Hospital and Faculty of
      Medicine, Masaryk University, Brno; Biopticka laborator Ltd., Pilsen. METHODS AND
      RESULTS: Nowadays, there are non-invasive methods for more accurate and timely
      detection of uterine cervix lesions. Digital images of the uterine cervix can be
      analysed by a computer for characteristic features and colour patterns, which may
      enhance the objectivity of the colposcopic examination. Digital image processing
      technology and biomarkers detection (p16/Ki-67) are useful in liquid based
      cytology (LBC). At the molecular genetic level different tests are used to detect
      deoxy- or ribonucleic acid (DNA, RNA) of high-risk types of human papillomavirus
      (HR HPV). The introduction of HPV testing in screening procedures in the Czech
      Republic will further in-crease the sensitivity of screening. However, the most
      specific identification of cervical high-grade lesions appears to be an mRNA
      detection of oncogenes E6 and E7. The advanced method for the assessment of
      cervical lesion progress in HR HPV positive women is to determine the methylation
      of tumor supressor genes that normally prevents the cancer growth. CONCLUSION:
      Screening programs, inviting women to direct preventive gynecological
      examinations by health insurance, but also efficient utilization of available
      methods could lead to early detections of cervical dysplasias. KEYWORDS: cervical
      dysplasia and cancer, SIL, colposcopy, LBC, HPV, methylation, mRNA.

PMID- 25398155
TI  - [Intraindividual variability of uroflowmetry in women].
AB  - OBJECTIVE: The objective of this study was to determine the intraindividual
      variability of uroflowmetric measurement in women with normal lower urinary tract
      function. DESIGN: Prospective study. SETTING: Departure of obstetrics and
      gynecology University Hospital and Medical Faculty Ostrava. METHODS: 35 women
      without lower urinary tract dysfunction were enrolled into the study. Every
      subject uderwent 3 uroflowmetric examinations. We processed all numeric results.
      RESULTS: We assessed maximum and average urine flow rate - Qmax, Qave, voided
      volume - VV, corrected maximum urine flow and corrected average urine flow rate
      in every of 105 uroflowmetric's measurements. We did not find any statistically
      significant difference for evaluation of intraindividual dispersion in studied
      parameters. CONCLUSION: Intraindividual variability of uroflowmetric's
      measurement in healthy female subjects is low. One uroflowmetric's measurement is
      adequate for assessment of uroflowmetric's parameters.. KEYWORDS: uroflowmetry,
      intraindividual variability, lower urinary tract.

PMID- 25398156
TI  - [Principles and limits of clinical methods in the diagnosis of fetal hypoxia].
AB  - OBJECTIVE: An overview of electronic fetal monitoring methods (EFM), and an
      analysis of their physical and technical limits. DESIGN: A review article.
      SETTING: Department of Gynecology and Obstetrics Jessenius Faculty of Medicine in
      Martin, Comenius University in Bratislava, Slovak Republic. METHODS: An analysis
      of the literature using database search engines PubMed, and SCOPE in the years
      2000 - 2013 in field of diagnostic methods of fetal status in utero. RESULTS: The
      essential aim of modern perinatology is the birth of a live and healthy newborn.
      This aim is strongly related to the abilities of the diagnostic methods to
      evaluate the intrauterine fetal status and with the professional skills of
      obstetricians to analyze these methods accurately. Nowadays, EFM is exposed to
      criticism, in spite of its widespread use. It is associated with some degree of
      failure in terms of an over-evaluation and under-evaluation. An over-evaluation
      of results can lead to unnecessary, often surgical, intervention. An under
      evaluation of results can lead to an adverse fetal outcome with a neurologic
      handicap or intrauterine death. The long-term efforts currently underway to
      improve the reliability of EFM still remain to show any great progress. KEYWORDS:
      cardiotocography, intermittent auscultation, pulse oximetry, ST analysis, fetal
      electrocardiography.

PMID- 25398157
TI  - [Shute's parallel forceps].
AB  - By invention of his forceps in 1950's W. B. Shute introduces a new principle of
      parallelism, which is characterised by higher safety for the foetus. The main
      advantage is that the force acting on the head can be exactly controlled. Authors
      explain design and use of the instrument which is, by it's indications and
      versatility, similar to Kjelland's forceps. Literary review is cited and brief
      biografy of inventor is added. Where Shute's instrument is available, priority
      shoud be given to it, as parallel forceps exceeds the Kjelland's one by it's
      safety for the foetus and moreover is easier to use and to learn too. KEYWORDS:
      parallel forceps, W. B Shute, obstetrical operations, obstetrical forceps.

PMID- 25398158
TI  - Electronic ferroelectricity in molecular organic crystals.
AB  - Electronic ferroelectricity in molecular organic crystals is reviewed from a
      theoretical perspective. In particular, we focus on the charge-driven-type
      electronic ferroelectricity where electronic charge order without inversion
      symmetry induces a spontaneous electric polarization in quarter-filling systems.
      Two necessary conditions to realize this type of ferroelectricity are the dimer
      type lattice structure and alternate electronic charge alignments. Some
      prototypical organic compounds are introduced. In particular, kappa-type BEDT-TTF
      organic salts, which are termed the dimer-Mott insulating systems, are focused
      on. Recent developments in the theoretical researches for dielectric and
      magnetodielectric properties, a collective dipole excitation and a possibility of
      superconductivity induced by polar charge fluctuation are reviewed. Some
      perspectives are presented. 

PMID- 25398159
TI  - Ground state, collective mode, phase soliton and vortex in multiband
      superconductors.
AB  - This article reviews theoretical and experimental work on the novel physics in
      multiband superconductors. Multiband superconductors are characterized by
      multiple superconducting energy gaps in different bands with interaction between
      Cooper pairs in these bands. The discovery of prominent multiband superconductors
      MgB2 and later iron-based superconductors, has triggered enormous interest in
      multiband superconductors. The most recently discovered superconductors exhibit
      multiband features. The multiband superconductors possess novel properties that
      are not shared with their single-band counterpart. Examples include: the time
      reversal symmetry broken state in multiband superconductors with frustrated
      interband couplings; the collective oscillation of number of Cooper pairs between
      different bands, known as the Leggett mode; and the phase soliton and fractional
      vortex, which are the main focus of this review. This review presents a survey of
      a wide range of theoretical exploratory and experimental investigations of novel
      physics in multiband superconductors. A vast amount of information derived from
      these studies is shown to highlight unusual and unique properties of multiband
      superconductors and to reveal the challenges and opportunities in the research on
      the multiband superconductivity. 

PMID- 25398161
TI  - Thermal conductivity and energetic recoils in UO2 using a many-body potential
      model.
AB  - Classical molecular dynamics simulations have been performed on uranium dioxide
      (UO2) employing a recently developed many-body potential model. Thermal
      conductivities are computed for a defect free UO2 lattice and a radiation
      damaged, defect containing lattice at 300 K, 1000 K and 1500 K. Defects
      significantly degrade the thermal conductivity of UO2 as does the presence of
      amorphous UO2, which has a largely temperature independent thermal conductivity
      of ~1.4 Wm(-1) K(-1). The model yields a pre-melting superionic transition
      temperature at 2600 K, very close to the experimental value and the mechanical
      melting temperature of 3600 K, slightly lower than those generated with other
      empirical potentials. The average threshold displacement energy was calculated to
      be 37 eV. Although the spatial extent of a 1 keV U cascade is very similar to
      those generated with other empirical potentials and the number of Frenkel pairs
      generated is close to that from the Basak potential, the vacancy and interstitial
      cluster distribution is different. 

PMID- 25398160
TI  - Routine perineal shaving on admission in labour.
AB  - BackgroundPubic or perineal shaving is a procedure performed before birth in
      order to lessen the risk of infection if there is a spontaneous perinealtear or
      if an episiotomy is performed.ObjectivesTo assess the effects of routine perineal
      shaving before birth onmaternal and neonatal outcomes, according to the best
      available evidence.Search methodsWe searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (12 June 2014).Selection criteriaAll
      controlled trials (including quasi-randomised) that compare perineal shaving
      versus no perineal shaving.Data collection and analysisTwo review authors
      independently assessed all potential studies for inclusion, assessed risk of bias
      and extracted the data using apredesigned form. Data were checked for
      accuracy.Main resultsThree randomised controlled trials (1039 women) published
      between 1922 and 2005 fulfilled the prespecified criteria. In the earliesttrial,
      389 women were alternately allocated to receive either skin preparation and
      perineal shaving or clipping of vulval hair only. In thesecond trial, which
      included 150 participants, perineal shaving was compared with the cutting of long
      hairs for procedures only. In thethird and most recent trial, 500 women were
      randomly allocated to shaving of perineal area or cutting of perineal hair. The
      primaryoutcome for all three trials was maternal febrile morbidity; no
      differences were found (risk ratio (RR) 1.14, 95% confidence interval(CI) 0.73 to
      1.76). No differences were found in terms of perineal wound infection (RR 1.47,
      95% CI 0.80 to 2.70) and perinealwound dehiscence (RR 0.33, 95% CI 0.01 to 8.00)
      in the most recent trial involving 500 women, which was the only trial to
      assessthese outcomes. In the smallest trial, fewer women who had not been shaved
      had Gram-negative bacterial colonisation compared withwomen who had been shaved
      (RR 0.83, 95% CI 0.70 to 0.98). There were no instances of neonatal infection in
      either group in theone trial that reported this outcome. There were no
      differences in maternal satisfaction between groups in the larger trial reporting
      this outcome (mean difference (MD) 0.00, 95% CI -0.13 to 0.13). No trial reported
      on perineal trauma. One trial reported on side-effectsand these included
      irritation, redness, burning and itching.The overall quality of evidence ranged
      from very low (for the outcomes postpartum maternal febrile morbidity and
      neonatal infection)to low (for the outcome maternal satisfaction and wound
      infection).Authors' conclusionsThere is insufficient evidence to recommend
      perineal shaving for women on admission in labour.

PMID- 25398162
TI  - Probiotics and allergies: myth or reality?
AB  - During the last years, along with the growing knowledge about the role and
      importance of the intestinal flora, interest remarkably increased in probiotic
      bacteria supplementation. It has indeed been demonstrated that the intestinal
      microbiota is very important in the regulation of several functions of the
      organism, even those far from the gastro-enteric system. Among them, great
      interest was stimulated by the proven capability of the intestinal microbiota to
      regulate the immune system, in particular to rebalance the TH1/Th2 ratio.
      Consequence thereof is the assumption that the administration of probiotic
      bacteria may induce clinical benefits in allergic pathologies. Many clinical
      studies have been carried out that considered the possibility of preventing
      allergic sensitizations, and preventing and treating atopic dermatitis and
      allergic rhinitis. Many studies demonstrated that the administration of
      probiotics is able to prevent the onset of allergic sensitizations and improve
      the symptoms of atopic dermatitis and allergic rhinitis; however, studies were
      published, too, that achieved negative outcomes. The overall evaluation of
      results is, however, difficult, as the strains used and the study design are
      markedly heterogeneous. Future investigations with a better standardization will
      be able to better explain the role of the intestinal flora in atopy, and the role
      of probiotics in the treatment of allergic diseases. 

PMID- 25398163
TI  - Neuropathy in eosinophilic granulomatosis with polyangiitis: a comparison study
      of 24 cases with or without prior leukotriene antagonist exposure.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss
      syndrome (CSS), is a systemic vasculitis affecting almost exclusively patients
      with asthma. Neuropathy is the presenting feature in 55-75 % of cases. An
      increased incidence of the syndrome has been reported in asthmatics treated with
      leukotriene antagonists (LTAs). The causal relation is still debated. We
      retrospectively examined clinical, biochemical, histological features, and
      outcome of patients referred between 1990 and 2006 for sural nerve biopsy
      affected by neuropathy related to EGPA. We identified 24 patients, 6 treated with
      LTA montelukast (T-group) and 18 not treated (NT-Group). All had chronic asthma;
      in T-group neuropathy developed from 1 to 150 days after starting montelukast.
      Demographic features as well as asthma duration and pre-onset treatment were
      remarkably similar, with the only exception of a statistically nonsignificant
      larger involvement of the nasal mucosa in T group. Nerve biopsy revealed in both
      group an axonal neuropathy. At follow-up, all within the T-group and most within
      the NT-group improved clinically; neurophysiological parameters remained stable,
      improved or worsened in the same proportion within the two groups. Only 2 NT and
      no T-patient had stopped steroid treatment before the appearance of the
      peripheral neuropathy, making withdrawal overall unlikely as a causative factor
      of the onset of neuropathy. In summary, the temporal relationship between
      montelukast administration and the onset of neuropathy, would make the latter
      more likely as an "adverse drug reaction". Despite this, no significant clinical
      neither neurophysiological differences were noted between the two groups. 

PMID- 25398164
TI  - Subtypes of chronic urticaria in patients attending allergy clinics in Venezuela.
AB  - Chronic urticaria (CU) is one of the most puzzling clinical entities confronted
      by the medical profession. It is a common motive for consultation, and in a
      sizable proportion of patients no identifiable cause is evident. Since there are
      relatively few publications regarding CU in developing countries, we performed a
      prospective 3-year study on the demographic and clinical features of patients
      with CU. Four hundred and twenty-three subjects were studied, 52 children and 371
      adults, 295 females (69.7%), with a mean age of 38.4 +/- 17.8 years. More often,
      wheals and angioedema (AE) were present on the head, upper and lower limbs and
      the trunk. AE was present in 162 patients (38.4%). The most frequent subtypes
      were chronic spontaneous urticaria, aspirin-exacerbated cutaneous disease,
      dermographic urticaria, and combinations of various subtypes. A better
      understanding of the characteristics of patients suffering CU is helpful for
      clinicians dealing with this ailment, and provides guidance for new
      investigations on its pathogenesis, which will hopefully result in a better
      management of this vexing condition. 

PMID- 25398165
TI  - Pilot study on the short-term prediction of symptoms in children with hay fever
      monitored with e-Health technology.
AB  - Forecasting symptoms of pollen-related allergic rhinoconjunctivitis at the level
      of individual patients would be useful to improve disease control and plan
      pharmacological intervention. Information Technology nowadays facilitates a more
      efficient and easier monitoring of patients with chronic diseases. We aimed this
      study at testing the efficiency of a model to short-term forecast symptoms of
      pollen-AR at the "individual" patient level. We analysed the data prospectively
      acquired from a group of 21 Italian children affected by pollen-related allergic
      rhinoconjunctivitis and recorded their symptoms and medication "Average Combined
      Score" (ACS) on a daily basis during April-June 2010-2011 through an informatics
      platform (AllergymonitorTM). The dataset used for prediction included 15
      variables in four categories: (A) date, (B) meteo-climatic, (C) atmospheric
      concentration of 5 pollen taxa, and (D) intensity of the patient's IgE
      sensitization. A Partial Least Squares Discriminant Analysis approach was used in
      order to predict ACS values above a fixed threshold value (0.5). The best
      performing predicting model correctly classified 77.8% +/- 10.3% and 75.5% +/-
      13.2% of the recorded days in the model and test years, respectively. In this
      model, 9/21 patients showed >= 80% correct classification of the recorded days in
      both years. A better performance was associated with a higher degree of patient's
      atopic sensitization and a time lag > 1. Symptom forecasts of seasonal allergic
      rhinitis are possible in highly polysensitised patients in areas with complex
      pollen exposure. However, only predictive models tailored to the individual
      patient's allergic susceptibility are accurate enough. Multicenter studies in
      large population samples adopting the same acquisition data system on smart
      phones are now needed to confirm this encouraging outcome. 

PMID- 25398166
TI  - Omalizumab treatment in patient with severe asthma and Eosinophilic
      Granulomatosis with Polyangiitis . A case report.
AB  - Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly named Churg
      Strauss Syndrome, is a multisystem disorder characterized by chronic
      rhinosinusitis, asthma, and prominent peripheral blood eosinophilia; it is
      classified as a vasculitis of the small and medium sized arteries, although the
      vasculitis is often not clinically apparent in the initial phases of the disease.
      We present the case of a woman with EGPA who was frequently treated with high
      dose steroid therapy during hospital admission for refractory asthma. After
      December 2008, the date when we started Omalizumab, we observed a significative
      reduction of circulating eosinophils and IgE serum level, and the patient was no
      more hospitalized for respiratory failure or asthma attacks. 

PMID- 25398167
TI  - Hyperimmunoglobulinemia E and efficacy of elimination diet in two patients with
      Schnitzler syndrome.
AB  - BACKGROUND: Schnitzler syndrome (SS) is a rare clinical entity characterized by
      chronic recurrent urticarial rash, monoclonal IgM gammopathy, intermittent fever
      and other symptoms. In this report, we present the cases of two patients with SS:
      a male and a female aged 50 and 49 years, respectively. Both patients had
      hyperimmunoglobulinemia E and showed good response to elimination diet. METHODS:
      The patients had chronic urticaria, IgM gammopathy and an elevation of the serum
      levels of inflammation markers. Total IgE levels were found to be high (2000 U/ml
      and 540 U/ml, respectively). No underlying causes for hyperimmunoglobulinemia E
      (allergy, parasites, etc.) were revealed. The first patient did not respond to
      the treatment with antihistamines, while the second one responded only to high
      doses. The response to prednisolone in the second patient was incomplete.
      RESULTS: Following a strict elimination diet resulted in marked improvement in
      skin lesions in both patients. In one of our patients we observed a decrease in
      IgE and IgM levels after a 3 week diet. The systemic symptoms persisted and
      improved only after adding pefloxacin, followed by a 3-day empirical course of
      intravenous prednisone in the first patient and a course of plasmapheresis in the
      second one. CONCLUSION: The high serum levels of total IgE may be associated with
      chronic urticaria activity, severe disease course and a poor response to
      treatment with antihistamines, and may be considered a possible marker of a
      subset of patients with SS showing a good response to the restriction diet. In
      general, we can assume that elimination diet can have an influence on the skin
      lesions and other symptoms of SS as well as on total IgE and IgM levels, but such
      association, the underlying mechanisms and the reasons for excessive IgE
      synthesis should be investigated in further studies.

PMID- 25398168
TI  - New risks from ancient food dyes: cochineal red allergy.
AB  - This study reports an unusual case of IgE-mediated hypersensitivity to Cochineal
      red or Carmine red, a coloring agent of natural origin. Although the risk of
      anaphylactic reactions is well known, since the nineties the use of this additive
      seems to be nowadays on the rise. The problem of labeling of additives used in
      handmade food products is highlighted. 

PMID- 25398169
TI  - "Overlapped" rhinitis: a real trap for rhinoallergologists.
AB  - Under the broad heading of "vasomotor" rhinitis two big groups can be
      distinguished: allergic rhinitis (IgE-mediated), and nonallergic rhinitis. Since
      they are two separate nosological entities, they can co-exist in the same
      patient, classifying themselves in the group of "overlapped" rhinitis (OR).
      Although not absolutely rare (indeed it is estimated a 15-20% incidence among all
      vasomotor rhinopathies), this condition is not investigated and diagnosed, with
      significant implications in the clinical-diagnostic and therapeutic field. 

PMID- 25398170
TI  - The importance of educating subjects entitled to use an adrenaline auto-injector
      for self-administration.
AB  - An educational program, consisting in a clear explanation of the technical
      aspects and use of the adrenaline auto-injection devices (AAD) and in a practical
      test utilizing a demonstration kit was given to 350 patients from our outpatient
      clinic. AAD was also distributed to 50 patients formerly followed by another
      allergy clinic without training. At practical control test, only 10% of the
      untrained patients where able to correctly use the AAD versus 80% of trained
      subjects. Since AAD is a life-saving procedure in severe anaphylactic episodes,
      this attempt to improve the ability of the patient to comply with the procedure
      can improve the efficacy of the treatment and eventually the patient's health. 

PMID- 25398172
TI  - A novel EOG/EEG hybrid human-machine interface adopting eye movements and ERPs:
      application to robot control.
AB  - This study presents a novel human-machine interface (HMI) based on both
      electrooculography (EOG) and electroencephalography (EEG). This hybrid interface
      works in two modes: an EOG mode recognizes eye movements such as blinks, and an
      EEG mode detects event related potentials (ERPs) like P300. While both eye
      movements and ERPs have been separately used for implementing assistive
      interfaces, which help patients with motor disabilities in performing daily
      tasks, the proposed hybrid interface integrates them together. In this way, both
      the eye movements and ERPs complement each other. Therefore, it can provide a
      better efficiency and a wider scope of application. In this study, we design a
      threshold algorithm that can recognize four kinds of eye movements including
      blink, wink, gaze, and frown. In addition, an oddball paradigm with stimuli of
      inverted faces is used to evoke multiple ERP components including P300, N170, and
      VPP. To verify the effectiveness of the proposed system, two different online
      experiments are carried out. One is to control a multifunctional humanoid robot,
      and the other is to control four mobile robots. In both experiments, the subjects
      can complete tasks effectively by using the proposed interface, whereas the best
      completion time is relatively short and very close to the one operated by hand. 

PMID- 25398174
TI  - Adhesive RFID Sensor Patch for Monitoring of Sweat Electrolytes.
AB  - Wearable digital health devices are dominantly found in rigid form factors such
      as bracelets and pucks. An adhesive radio-frequency identification (RFID) sensor
      bandage (patch) is reported, which can be made completely intimate with human
      skin, a distinct advantage for chronological monitoring of biomarkers in sweat.
      In this demonstration, a commercial RFID chip is adapted with minimum components
      to allow potentiometric sensing of solutes in sweat, and surface temperature, as
      read by an Android smartphone app with 96% accuracy at 50 mM Na(+) (in vitro
      tests). All circuitry is solder-reflow integrated on a standard Cu/polyimide
      flexible-electronic layer including an antenna, but while also allowing
      electroplating for simple integration of exotic metals for sensing electrodes.
      Optional paper microfluidics wick sweat from a sweat porous adhesive allowing
      flow to the sensor, or the sensor can be directly contacted to the skin. The
      wearability of the patch has been demonstrated for up to seven days, and includes
      a protective textile which provides a feel and appearance similar to a standard
      Band-Aid. Applications include hydration monitoring, but the basic capability is
      extendable to other mM ionic solutes in sweat (Cl(-), K(+), Mg(2+), NH4(+), and
      Zn(2+)). The design and fabrication of the patch are provided in full detail, as
      the basic components could be useful in the design of other wearable sensors. 

PMID- 25398173
TI  - Characterization of force and torque interactions during a simulated transgastric
      appendectomy procedure.
AB  - We have developed an instrumented endoscope grip handle equipped with a six-axis
      load cell and measured forces and torques during a simulated transgastric natural
      orifice translumenal endoscopic surgery appendectomy procedure performed in an
      EASIE-R ex vivo simulator. The data were collected from ten participating
      surgeons of varying degrees of expertise which was analyzed to compute a set of
      six force and torque parameters for each coordinate axis for each of the nine
      tasks of the appendectomy procedure. The mean push/pull force was found to be
      3.64 N (sigma = 3.54 N) in the push direction and the mean torque was 3.3 N . mm
      (sigma = 38.6 N . mm) in the counterclockwise direction about the push/pull axis.
      Most interestingly, the force and torque data about the nondominant x and z axes
      showed a statistically significant difference (p < 0.05) between the expert and
      novice groups for five of the nine tasks. These data may be useful in developing
      surgical platforms especially new haptic devices and simulation systems for
      emerging natural orifice procedures.

PMID- 25398175
TI  - Diamagnetic levitation promotes osteoclast differentiation from RAW264.7 cells.
AB  - The superconducting magnet with a high magnetic force field can levitate
      diamagnetic materials. In this study, a specially designed superconducting magnet
      with large gradient high magnetic field (LGHMF), which provides three apparent
      gravity levels (MUg, 1 g, and 2 g), was used to study its influence on receptor
      activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast
      differentiation from preosteoclast cell line RAW264.7. The effects of LGHMF on
      the viability, nitric oxide (NO) production, morphology in RAW264.7 cells were
      detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) method, the Griess method, and the immunofluorescence staining,
      respectively. The changes induced by LGHMF in osteoclast formation, mRNA
      expression, and bone resorption were determined by tartrate-resistant acid
      phosphatase staining, semiquantity PCR, and bone resorption test, respectively.
      The results showed that: 1) LGHMF had no lethal effect on osteoclast precursors
      but attenuated NO release in RAW264.7 cells. 2) Diamagnetic levitation (MUg)
      enhanced both the formation and bone resorption capacity of osteoclast. Moreover,
      diamagnetic levitation up-regulated mRNA expression of RANK, Cathepsin K, MMP-9,
      and NFATc1, while down-regulated RunX2 in comparison with controls. Furthermore,
      diamagnetic levitation induced obvious morphological alterations in osteoclast,
      including active cytoplasmic peripheral pseudopodial expansion, formation of
      pedosome belt, and aggregation of actin ring. 3) Magnetic field produced by LGHMF
      attenuated osteoclast resorption activity. Collectively, LGHMF with combined
      effects has multiple effects on osteoclast, which attenuated osteoclast
      resorption with magnetic field, whereas promoted osteoclast differentiation with
      diamagnetic levitation. Therefore, these findings indicate that diamagnetic
      levitation could be used as a novel ground-based microgravity simulator, which
      facilitates bone cell research of weightlessness condition.

PMID- 25398176
TI  - A new method to measure directional modulation transfer function using sphere
      phantoms in a cone beam computed tomography system.
AB  - We propose a new method to measure directional modulation transfer function (MTF)
      using sphere phantoms in a cone beam computed tomography (CBCT) system. To
      measure spatially varying 3-D MTFs, we model FDK reconstruction in local regions
      and calculate the plane integrals of an ideal sphere phantom and reconstructed
      sphere phantoms. Then, we modify the Richardson-Lucy (RL) deconvolution method to
      relax the non-negativity constraint in RL deconvolution and apply it to estimate
      the directional plane spread functions (PlSFs). Directional MTFs are calculated
      by taking the modulus of the Fourier transform of the estimated directional
      PlSFs. To validate the proposed method, we simulate ideal 3-D MTFs and compare
      them with directional MTFs measured by simulation and experimental data along
      three major axes. For quantitative evaluation, we compare full-width at half
      maximum (FWHM) and full-width at tenth-maximum (FWTM) of measured and ideal
      directional MTFs. The measured directional MTFs from simulation and experimental
      data show excellent agreement with the ideal directional MTFs, demonstrating the
      effectiveness of the proposed method to estimate directional MTFs in a CBCT
      system. 

PMID- 25398177
TI  - Alternating direction method of multipliers for nonlinear image restoration
      problems.
AB  - In this paper, we address the total variation (TV)-based nonlinear image
      restoration problems. In nonlinear image restoration problems, an original image
      is corrupted by a spatially-invariant blur, the build-in nonlinearity in imaging
      system, and the additive Gaussian white noise. We study the objective function
      consisting of the nonlinear least squares data-fitting term and the TV
      regularization term of the restored image. By making use of the structure of the
      objective function, an efficient alternating direction method of multipliers can
      be developed for solving the proposed model. The convergence of the numerical
      scheme is also studied. Numerical examples, including nonlinear image restoration
      and high-dynamic range imaging are reported to demonstrate the effectiveness of
      the proposed model and the efficiency of the proposed numerical scheme. 

PMID- 25398178
TI  - On the efficiency of angular intraprediction.
AB  - Angular intraprediction (AIP) is a coding tool that has been incorporated into
      the video coding standards H.264/AVC (Advanced Audio Coding) and High Efficient
      Video Coding. In this paper, we study how the efficiency of AIP depends on its
      prediction parameters. To carry out this paper, we first theoretically analyze
      the variance of the error incurred when a perfectly directional signal is
      predicted in a certain direction. The results of this analysis are then used to
      study the efficiency of AIP when it is applied to a distribution of directions.
      To facilitate mathematical derivations, we make several assumptions about the
      signal and the prediction process, and we use some approximations. This allows us
      to obtain simple expressions for the variance of the AIP prediction error as a
      function of signal and prediction parameters. Finally, we compare our theoretical
      results with the results obtained from the prediction of images containing
      rectilinear edges. This comparison shows that our theoretical expressions follow
      the main trends of the experimental results except when AIP is performed with a
      very high accuracy.

PMID- 25398179
TI  - Learning templates for artistic portrait lighting analysis.
AB  - Lighting is a key factor in creating impressive artistic portraits. In this
      paper, we propose to analyze portrait lighting by learning templates of lighting
      styles. Inspired by the experience of artists, we first define several novel
      features that describe the local contrasts in various face regions. The most
      informative features are then selected with a stepwise feature pursuit algorithm
      to derive the templates of various lighting styles. After that, the matching
      scores that measure the similarity between a testing portrait and those templates
      are calculated for lighting style classification. Furthermore, we train a
      regression model by the subjective scores and the feature responses of a template
      to predict the score of a portrait lighting quality. Based on the templates, a
      novel face illumination descriptor is defined to measure the difference between
      two portrait lightings. Experimental results show that the learned templates can
      well describe the lighting styles, whereas the proposed approach can assess the
      lighting quality of artistic portraits as human being does. 

PMID- 25398180
TI  - The mesh-LBP: a framework for extracting local binary patterns from discrete
      manifolds.
AB  - In this paper, we present a novel and original framework, which we dubbed mesh
      local binary pattern (LBP), for computing local binary-like-patterns on a
      triangular-mesh manifold. This framework can be adapted to all the LBP variants
      employed in 2D image analysis. As such, it allows extending the related
      techniques to mesh surfaces. After describing the foundations, the construction
      and the main features of the mesh-LBP, we derive its possible variants and show
      how they can extend most of the 2D-LBP variants to the mesh manifold. In the
      experiments, we give evidence of the presence of the uniformity aspect in the
      mesh-LBP, similar to the one noticed in the 2D-LBP. We also report repeatability
      experiments that confirm, in particular, the rotation-invariance of mesh-LBP
      descriptors. Furthermore, we analyze the potential of mesh-LBP for the task of 3D
      texture classification of triangular-mesh surfaces collected from public data
      sets. Comparison with state-of-the-art surface descriptors, as well as with 2D
      LBP counterparts applied on depth images, also evidences the effectiveness of the
      proposed framework. Finally, we illustrate the robustness of the mesh-LBP with
      respect to the class of mesh irregularity typical to 3D surface-digitizer scans. 

PMID- 25398181
TI  - Ability of Low-Cost Force-Feedback Device to Influence Postural Stability.
AB  - Low-cost gaming technology offers promising devices for the rehabilitation of
      stroke patients at home. While several attempts have been made to use low-cost
      motion tracking devices (Kinect) or balance boards (Wii Board), the potential of
      low-cost haptic devices has yet to be explored in this context. The objective of
      this study was to investigate whether it is possible to influence postural
      stability with a low-cost device despite its technical limitations, and to
      explore the most promising modes of haptic interaction to increase and decrease
      postural stability. Two groups of younger subjects used a high-end (Omega.3) and
      a low-cost (Falcon) device respectively. A third group of older subjects used the
      Falcon. We show that light touch contact with the device improves stability,
      whereas the force tasks decrease it. The effects of the different tasks are
      consistent in the two age groups. Although there are differences in the
      participants' interaction with the two devices, the effect of the devices on
      postural stability is comparable. We conclude that a low-cost haptic device can
      be used to increase or decrease postural stability of healthy subjects with an
      age similar to that of typical stroke patients, in a safe and controllable way. 

PMID- 25398182
TI  - Multiscale layered biomechanical model of the pacinian corpuscle.
AB  - This paper describes a multiscale analytical model of the lamellar structure and
      the biomechanical response of the Pacinian Corpuscle (PC). In order to analyze
      the contribution of the PC lamellar structure for detecting high-frequency
      vibrotactile (VT) stimuli covering 10 Hz to a few kHz, the model response is
      studied against trapezoidal and sinusoidal stimuli. The model identifies a few
      generalizable features of the lamellar structure which makes it scalable for
      different sizes of PC with different number of lamellae. The model describes the
      mechanical signal conditioning of the lamellar structure in terms of a recursive
      transfer-function, termed as the Compression-Transmittance-Transfer-Function
      (CTTF). The analytical results show that with the increase of the PC layer index
      above 15, the PC inner core (IC) relaxes within 1 ms against step compression of
      the outermost layer. This model also considers the mass of each PC layer to
      investigate its effect on the biomechanical response of the lamellar structure.
      The interlamellar spacing and its biomechanical properties along with the model
      response are validated with experimental data in the literature. The proposed
      model can be used for simulating a network of PCs considering their diversity for
      analyzing the high-frequency VT sensitivity of the human skin. 

PMID- 25398183
TI  - Vibrotactile sensitivity threshold: nonlinear stochastic mechanotransduction
      model of the Pacinian Corpuscle.
AB  - Based on recent discoveries of stretch and voltage activated ion channels in the
      receptive area of the Pacinian Corpuscle (PC), this paper describes a two-stage
      mechanotransduction model of its near threshold Vibrotactile (VT) sensitivity
      valid over 10 Hz to a few kHz. The model is based on the nonlinear and stochastic
      behavior of the ion channels represented as dependent charge sources loaded with
      membrane impedance. It simulates the neural response of the PC considering the
      morphological and statistical properties of the receptor potential and action
      potential with the help of an adaptive relaxation pulse frequency modulator. This
      model also simulates the plateaus and nonmonotonic saturation of spike rate
      characteristics. The stochastic simulation based on the addition of mechanical
      and neural noise describes that the VT Sensitivity Threshold (VTST) at higher
      frequencies is more noise dependent. Above 800 Hz even a SNR = 150 improves the
      neurophysiological VTST more than 3 dBMU. In that frequency range, an absence of
      the entrainment threshold and a lower sensitivity index near the absolute
      threshold make the upper bound of the psychophysical VTST more dependent on the
      experimental protocol and physical set-up. This model can be extended to simulate
      the neural response of a group of PCs. 

PMID- 25398184
TI  - Volume Preserved Mass-Spring Model with Novel Constraints for Soft Tissue
      Deformation.
AB  - An interactive surgical simulation system needs to meet three main requirements,
      speed, accuracy, and stability. In this paper, we present a stable and accurate
      method for animating mass-spring systems in real time. An integration scheme
      derived from explicit integration is used to obtain interactive realistic
      animation for a multiobject environment. We explore a predictor-corrector
      approach by correcting the estimation of the explicit integration in a poststep
      process. We introduce novel constraints on positions into the mass-spring model
      (MSM) to model the nonlinearity and preserve volume for the realistic simulation
      of the incompressibility. We verify the proposed MSM by comparing its
      deformations with the reference deformations of the nonlinear finite-element
      method. Moreover, experiments on porcine organs are designed for the evaluation
      of the multiobject deformation. Using a pair of freshly harvested porcine liver
      and gallbladder, the real organ deformations are acquired by computed tomography
      and used as the reference ground truth. Compared to the porcine model, our model
      achieves a 1.502 mm mean absolute error measured at landmark locations for cases
      with small deformation (the largest deformation is 49.109 mm) and a 3.639 mm mean
      absolute error for cases with large deformation (the largest deformation is
      83.137 mm). The changes of volume for the two deformations are limited to 0.030%
      and 0.057%, respectively. Finally, an implementation in a virtual reality
      environment for laparoscopic cholecystectomy demonstrates that our model is
      capable to simulate large deformation and preserve volume in real-time
      calculations. 

PMID- 25398185
TI  - Evolutionary Fuzzy Control and Navigation for Two Wheeled Robots Cooperatively
      Carrying an Object in Unknown Environments.
AB  - This paper presents a method that allows two wheeled, mobile robots to navigate
      unknown environments while cooperatively carrying an object. In the navigation
      method, a leader robot and a follower robot cooperatively perform either obstacle
      boundary following (OBF) or target seeking (TS) to reach a destination. The two
      robots are controlled by fuzzy controllers (FC) whose rules are learned through
      an adaptive fusion of continuous ant colony optimization and particle swarm
      optimization (AF-CACPSO), which avoids the time-consuming task of manually
      designing the controllers. The AF-CACPSO-based evolutionary fuzzy control
      approach is first applied to the control of a single robot to perform OBF. The
      learning approach is then applied to achieve cooperative OBF with two robots,
      where an auxiliary FC designed with the AF-CACPSO is used to control the follower
      robot. For cooperative TS, a rule for coordination of the two robots is
      developed. To navigate cooperatively, a cooperative behavior supervisor is
      introduced to select between cooperative OBF and cooperative TS. The performance
      of the AF-CACPSO is verified through comparisons with various population-based
      optimization algorithms for the OBF learning problem. Simulations and experiments
      verify the effectiveness of the approach for cooperative navigation of two
      robots. 

PMID- 25398186
TI  - Approximation-Based Adaptive Tracking Control for MIMO Nonlinear Systems With
      Input Saturation.
AB  - In this paper, an approximation-based adaptive tracking control approach is
      proposed for a class of multiinput multioutput nonlinear systems. Based on the
      method of neural network, a novel adaptive controller is designed via
      backstepping design process. Furthermore, by introducing Nussbaum function, the
      issue of unknown control directions is handled. In the backstepping design
      process, the dynamic surface control technique is employed to avoid
      differentiating certain nonlinear functions repeatedly. Moreover, in order to
      reduce the number of adaptation laws, we do not use the neural networks to
      directly approximate the unknown nonlinear functions but the desired control
      signals. Finally, we provide two examples to illustrate the effectiveness of the
      proposed approach. 

PMID- 25398187
TI  - Treelets Binary Feature Retrieval for Fast Keypoint Recognition.
AB  - Fast keypoint recognition is essential to many vision tasks. In contrast to the
      classification-based approaches, we directly formulate the keypoint recognition
      as an image patch retrieval problem, which enjoys the merit of finding the
      matched keypoint and its pose simultaneously. To effectively extract the binary
      features from each patch surrounding the keypoint, we make use of treelets
      transform that can group the highly correlated data together and reduce the noise
      through the local analysis. Treelets is a multiresolution analysis tool, which
      provides an orthogonal basis to reflect the geometry of the noise-free data. To
      facilitate the real-world applications, we have proposed two novel approaches.
      One is the convolutional treelets that capture the image patch information
      locally and globally while reducing the computational cost. The other is the
      higher-order treelets that reflect the relationship between the rows and columns
      within image patch. An efficient sub-signature-based locality sensitive hashing
      scheme is employed for fast approximate nearest neighbor search in patch
      retrieval. Experimental evaluations on both synthetic data and the real-world
      Oxford dataset have shown that our proposed treelets binary feature retrieval
      methods outperform the state-of-the-art feature descriptors and classification
      based approaches. 

PMID- 25398188
TI  - A unified spatiotemporal modeling approach for predicting concentrations of
      multiple air pollutants in the multi-ethnic study of atherosclerosis and air
      pollution.
AB  - BACKGROUND: Cohort studies of the relationship between air pollution exposure and
      chronic health effects require predictions of exposure over long periods of time.
      OBJECTIVES: We developed a unified modeling approach for predicting fine
      particulate matter, nitrogen dioxide, oxides of nitrogen, and black carbon (as
      measured by light absorption coefficient) in six U.S. metropolitan regions from
      1999 through early 2012 as part of the Multi-Ethnic Study of Atherosclerosis and
      Air Pollution (MESA Air). METHODS: We obtained monitoring data from regulatory
      networks and supplemented those data with study-specific measurements collected
      from MESA Air community locations and participants' homes. In each region, we
      applied a spatiotemporal model that included a long-term spatial mean, time
      trends with spatially varying coefficients, and a spatiotemporal residual. The
      mean structure was derived from a large set of geographic covariates that was
      reduced using partial least-squares regression. We estimated time trends from
      observed time series and used spatial smoothing methods to borrow strength
      between observations. RESULTS: Prediction accuracy was high for most models, with
      cross-validation R2 (R2CV) > 0.80 at regulatory and fixed sites for most regions
      and pollutants. At home sites, overall R2CV ranged from 0.45 to 0.92, and
      temporally adjusted R2CV ranged from 0.23 to 0.92. CONCLUSIONS: This novel
      spatiotemporal modeling approach provides accurate fine-scale predictions in
      multiple regions for four pollutants. We have generated participant-specific
      predictions for MESA Air to investigate health effects of long-term air pollution
      exposures. These successes highlight modeling advances that can be adopted more
      widely in modern cohort studies.

PMID- 25398189
TI  - Exposure to household air pollution from wood combustion and association with
      respiratory symptoms and lung function in nonsmoking women: results from the
      RESPIRE trial, Guatemala.
AB  - BACKGROUND: With 40% of the world's population relying on solid fuel, household
      air pollution (HAP) represents a major preventable risk factor for COPD (chronic
      obstructive pulmonary disease). Meta-analyses have confirmed this relationship;
      however, constituent studies are observational, with virtually none measuring
      exposure directly. OBJECTIVES: We estimated associations between HAP exposure and
      respiratory symptoms and lung function in young, nonsmoking women in rural
      Guatemala, using measured carbon monoxide (CO) concentrations in exhaled breath
      and personal air to assess exposure. METHODS: The Randomized Exposure Study of
      Pollution Indoors and Respiratory Effects (RESPIRE) Guatemala study was a trial
      comparing respiratory outcomes among 504 women using improved chimney stoves
      versus traditional cookstoves. The present analysis included 456 women with data
      from postintervention surveys including interviews at 6, 12, and 18 months
      (respiratory symptoms) and spirometry and CO (ppm) in exhaled breath
      measurements. Personal CO was measured using passive diffusion tubes at variable
      times during the study. Associations between CO concentrations and respiratory
      health were estimated using random intercept regression models. RESULTS:
      Respiratory symptoms (cough, phlegm, wheeze, or chest tightness) during the
      previous 6 months were positively associated with breath CO measured at the same
      time of symptom reporting and with average personal CO concentrations during the
      follow-up period. CO in exhaled breath at the same time as spirometry was
      associated with lower lung function [average reduction in FEV1 (forced expiratory
      volume in 1 sec) for a 10% increase in CO was 3.33 mL (95% CI: -0.86, -5.81)].
      Lung function measures were not significantly associated with average
      postintervention personal CO concentrations. CONCLUSIONS: Our results provide
      further support for the effects of HAP exposures on airway inflammation. Further
      longitudinal research modeling continuous exposure to particulate matter against
      lung function will help us understand more fully the impact of HAP on COPD.

PMID- 25398190
TI  - Limitation in tidal volume expansion partially determines the intensity of
      physical activity in COPD.
AB  - In patients with chronic obstructive pulmonary disease (COPD), reduced levels of
      daily physical activity are associated with the degree of impairment in lung,
      peripheral muscle, and central hemodynamic function. There is, however, limited
      evidence as to whether limitations in tidal volume expansion also, importantly,
      determine daily physical activity levels in COPD. Eighteen consecutive patients
      with COPD [9 active (forced expiratory volume in 1 s, FEV1: 1.59 +/- 0.64 l) with
      an average daily movement intensity >1.88 m/s(2) and 9 less active patients
      (FEV1: 1.16 +/- 0.41 l) with an average intensity <1.88 m/s(2)] underwent a 4-min
      treadmill test at a constant speed corresponding to each individual patient's
      average movement intensity, captured by a triaxial accelerometer during a
      preceding 7-day period. When chest wall volumes, captured by optoelectronic
      plethysmography, were expressed relative to comparable levels of minute
      ventilation (ranging between 14.5 +/- 4.3 to 33.5 +/- 4.4 l/min), active patients
      differed from the less active ones in terms of the lower increase in end
      expiratory chest wall volume (by 0.15 +/- 0.17 vs. 0.45 +/- 0.21 l), the greater
      expansion in tidal volume (by 1.76 +/- 0.58 vs. 1.36 +/- 0.24 l), and the larger
      inspiratory reserve chest wall volume (IRVcw: by 0.81 +/- 0.25 vs. 0.39 +/- 0.27
      l). IRVcw (r(2) = 0.420), expiratory flow (r(2) change = 0.174), and Borg dyspnea
      score (r(2) change = 0.123) emerged as the best contributors, accounting for
      71.7% of the explained variance in daily movement intensity. Patients with COPD
      exhibiting greater ability to expand tidal volume and to maintain adequate
      inspiratory reserve volume tend to be more physically active. Thus interventions
      aiming at mitigating restrictions on operational chest wall volumes are expected
      to enhance daily physical activity levels in COPD. 

PMID- 25398191
TI  - [Diagnostics and treatment of syncope].
AB  - A transient loss of consciousness in the elderly is in most cases caused by
      syncope of cardiac origin. The underlying cause of syncope is of prognostic
      importance and should be clarified in every single case even if a definitive
      diagnosis can be established in only approximately two thirds of all cases. The
      definitive diagnosis is the key for appropriate therapeutic measures to prevent
      recurrences. Flowcharts can help to implement considerate and efficient stepwise
      diagnostic procedures. The most important diagnostic measures and treatment
      options according to medical evidence are presented. 

PMID- 25398192
TI  - 24-h multichannel intraluminal impedance-pH monitoring may be an inadequate test
      for detecting gastroesophageal reflux in patients with mixed typical and atypical
      symptoms.
AB  - BACKGROUND: The detection of gastroesophageal reflux (GERD) via pH testing is the
      key component of the evaluation of patients considered for antireflux surgery.
      Two common pH testing systems exist, a multichannel, intraluminal impedance-pH
      monitoring (MII-pH) catheter, and wireless (Bravo((r))) capsule; however,
      discrepancies between the two systems exist. In patients with atypical symptoms,
      MII-pH catheter is often used preferentially. We aimed to elucidate the magnitude
      of this discrepancy and to assess the diagnostic value of MII-pH and the Bravo
      wireless capsule in a population of patients with mixed respiratory and typical
      symptoms. METHODS: The study population consisted of 66 patients tested with MII
      pH and Bravo pH testing within 90 days between July 2009 and 2013. All patients
      presented with laryngo-pharyngo-respiratory (LPR) symptoms. Patient demographics,
      symptomatology, manometric and endoscopic findings, and pH monitoring parameters
      were analyzed. Patients were divided into four comparison groups: both pH tests
      positive, MII-pH negative/Bravo positive, MII-pH positive/Bravo negative, and
      both pH tests negative. RESULTS: Nearly half of the patients (44%) had discordant
      pH test results. Of these, 90% (26/29) had a negative MII-pH but positive Bravo
      study. In this group, the difference in the DeMeester score was large, a median
      of 29.3. These patients had a higher BMI (28.5 vs. 26.1, p = 0.0357), were more
      likely to complain of heartburn (50 vs. 23%, p = 0.0110), to have a hiatal
      hernia, (85 vs. 53%, p = 0.0075) and a structurally defective lower esophageal
      sphincter (LES, 85 vs. 58%, p = 0.0208). CONCLUSIONS: In patients with LPR
      symptoms, we found a high prevalence of discordant esophageal pH results, most
      commonly a negative MII-pH catheter and positive Bravo. As these patients
      exhibited characteristics consistent with GERD (heartburn, defective LES, hiatal
      hernia), the Bravo results are likely true. A 24-h MII-pH catheter study may be
      inadequate to diagnose GERD in this patient population.

PMID- 25398193
TI  - Timing and nature of presentation of unsuspected retained common bile duct stones
      after laparoscopic cholecystectomy: a retrospective study.
AB  - BACKGROUND: Common bile duct (CBD) stones may be over looked at the time of
      laparoscopic cholecystectomy (LC), particularly when intra-operative
      cholangiography (IOC) is not performed. Currently, there is no data available
      about the time course and pattern of presentation for stones retained in the CBD
      at the time of LC. The aim of this study was to establish the time course and
      pattern of presentation of unsuspected retained CBD stones post LC. METHODS:
      Patients presenting with symptomatic CBD stones from 1994 until 2010, having
      previously undergone LC were studied in this retrospective, case note review. CBD
      stones were confirmed at ERCP. Data collected included LC date, mode of
      presentation, imaging results including CBD diameter, stone appearance, length of
      stay and post ERCP complications. Patients having an ERCP for stones found on IOC
      at LC were excluded. RESULTS: Sixty-one patients met the inclusion criteria. The
      most common mode of presentation was abdominal pain (n = 38, 62%) with (17) or
      without (21) deranged liver function tests. Nineteen (31%) patients presented
      with clinical complications of the CBD stones: cholangitis (10), acute biliary
      pancreatitis (6) or obstructive jaundice (3). The CBD was usually mild-to
      moderately dilated (8-15 mm) on ultrasound. The median time span from LC to
      presentation with CBD stones was 4 years (range: 6 days-18 years). Five (8.2%)
      patients had a complication from their ERCP; mild pancreatitis (3), bleed (1) and
      cholangitis (1). Nineteen (31.1%) patients required more than one ERCP to
      complete stone/stent removal. CONCLUSIONS: The median time for patients to
      present with symptomatic CBD stones after LC is 4 years. Patients with retrained
      stones may remain asymptomatic for many years. A third of the patients presented
      with potentially serious complications of the retained CBD stone. Future studies
      for CBD stones after LC need to follow patients for at least 10 years.

PMID- 25398194
TI  - Update of guidelines on laparoscopic (TAPP) and endoscopic (TEP) treatment of
      inguinal hernia (International Endohernia Society).

PMID- 25398195
TI  - Enhanced recovery simulation in colorectal surgery: design of virtual online
      patients.
AB  - BACKGROUND: The aim of the present study was to design virtual patients (VP)
      involving enhanced recovery programs (ERP) in colorectal surgery, in order to
      train surgical residents in peri-operative care. Indeed, ERP have changed
      perioperative care and improved patients outcomes in colorectal surgery.
      Training, using online VP with different pre- and post-operative cases, may
      increase implementation of ERP. METHODS: Pre- and post-operative cases were built
      in the virtual world of Second LifeTM according to a linear string design method.
      All pre- and post-operative cases were storyboarded by a colorectal surgeon in
      accordance with guidelines in both ERP and colorectal surgery, and reviewed by an
      expert in colorectal surgery. RESULTS: Four pre-operative and five post-operative
      cases of VP undergoing colorectal surgery were designed, including both simple
      and complex cases. Comments were provided through case progression to allow
      autonomic practice (such as "prescribed", "this is not useful" or "the consultant
      does not agree with your decision"). Pre-operative cases involved knowledge in
      colorectal diseases and ERP such as pre-operative counseling, medical review,
      absence of bowel preparation in colonic surgery, absence of fasting, minimal
      length incision, and discharge plan. Post-operative cases involved uneventful and
      complicated outcomes in order to train in both simple implementation of ERP
      (absence of nasogastric tube, epidural analgesia, early use of oral analgesia,
      perioperative nutrition, early mobilization) and decision making for more complex
      cases. CONCLUSION: Virtual colorectal patients have been developed to train in
      ERP through pre- and post-operative cases. Such patients could be included in a
      whole pathway care training involving technical and non-technical skills.

PMID- 25398196
TI  - Evaluation of the possibility to use the plant-microbe interaction to stimulate
      radioactive 137Cs accumulation by plants in a contaminated farm field in
      Fukushima, Japan.
AB  - Field experiments in a contaminated farmland in Nihonmatsu city, Fukushima were
      conducted to assess the effectiveness of the plant-microbe interaction on removal
      of radiocesium. Before plowing, 93.3% of radiocesium was found in the top 5 cm
      layer (5,718 Bq kg DW(-1)). After plowing, Cs radioactivity in the 0-15 cm layer
      ranged from 2,037 to 3,277 Bq kg DW(-1). Based on sequential extraction, the
      percentage of available radiocesium (water soluble + exchangeable) was fewer than
      10% of the total radioactive Cs. The transfer of (137)Cs was investigated in
      three agricultural crops; komatsuna (four cultivars), Indian mustard and
      buckwheat, inoculated with a Bacillus or an Azospirillum strains. Except for
      komatsuna Nikko and Indian mustard, inoculation with both strains resulted in an
      increase of biomass production by the tested plants. The highest (137)Cs
      radioactivity concentration in above-ground parts was found in Bacillus
      inoculated komatsuna Nikko (121 Bq kg DW(-1)), accompanied with the highest
      (137)Cs TF (0.092). Furthermore, komatsuna Nikko-Bacillus and Indian mustard
      Azospirillum associations gave the highest (137)Cs removal, 131.5 and 113.8 Bq m(
      2), respectively. Despite the beneficial effect of inoculation, concentrations of
      (137)Cs and its transfer to the tested plants were not very high; consequently,
      removal of (137)Cs from soil would be very slow.

PMID- 25398197
TI  - Genetic variances of SNP loci for milk yield in dairy cattle.
AB  - Regression coefficients and genetic variances for 40,890 single nucleotide
      polymorphisms (SNPs) for milk yield were calculated using mixed model equations,
      with deregressed proof (DRP) as the dependent variable. Bulls were genotyped
      using the Illumina BovineSNP50 v2 BeadChip and SNPs were edited according the
      minor allele frequency (MAF) and high incidence of missing genotype. Evaluation
      was conducted in two rounds. In the preliminary round, the direct genetic values
      (DGVs) of all genotyped bulls (2,904) were computed and the absolute difference
      between the DGV and the input DRP of each bull was investigated. Bulls with an
      absolute difference greater than the mean absolute difference plus two standard
      deviations were eliminated from the data set prior to the final analysis (2,766
      bulls remaining). SNP regression coefficients from the final analysis had a mean
      absolute value of 0.506 kg and a standard deviation of 0.409 kg. The SNP with the
      highest regression coefficient and genetic variance was ARSBFGLNGS4939 on
      chromosome 14. This SNP is located within the gene DGAT1 (diacylglycerol O
      acyltransferase 1). Other SNPs with high regression coefficients and genetic
      variance are localised in proximity to DGAT1. The mean genetic variance of an
      individual SNP was 0.170, with a standard deviation of 0.384 and a mean
      heterozygosity of 0.372. The sum of genetic variances of all SNPs was only
      6,968.8, probably because of the existence of genetic covariances between loci.
      The largest sum of genetic variances was on chromosome 14 (498.4, 7.15 % of the
      total). After the final analysis, the correlation between the DGV and the input
      DRP was 0.951 for all bulls. The variance of the predicted DGV was 98.11 % of the
      variance of the input estimated breeding value (EBV) and 63.65 % of the variance
      of the DRP.

PMID- 25398198
TI  - Suicidality and posttraumatic stress disorder (PTSD) in adolescents: a systematic
      review and meta-analysis.
AB  - PURPOSE: There is growing evidence in the literature that a diagnosis of
      Posttraumatic Stress Disorder (PTSD) is an important contributory factor to
      suicidality in adolescents. However, there is no existing review of the
      literature examining the relationship between PTSD and suicidality in
      adolescents. This study aims to provide the first systematic review and meta
      analysis of the association between PTSD and suicidality in adolescents. METHODS:
      Five bibliographic databases (Medline, EMBASE, PsycINFO, Web of Science and
      PILOT) were screened for suitable articles. Twenty-eight studies (which provided
      28 independent samples) were included in the review. The overall meta-analyses of
      the association between PTSD and suicidality were followed by subgroup and meta
      regression analyses. RESULTS: A highly significant positive association was found
      between PTSD and suicidality (d = 0.701, 95% CI 0.555-0.848). The subgroup and
      meta-regression analyses showed that the association between PTSD and suicidality
      persisted whilst adjusting for various sources of between-study heterogeneity,
      such as, different levels of severity of suicidality, target groups, and
      methodological quality of the studies. CONCLUSIONS: Suicidality in adolescents
      with PTSD is a major problem which requires further research effort. The
      implications of these results are discussed.

PMID- 25398199
TI  - Loss of social resources predicts incident posttraumatic stress disorder during
      ongoing political violence within the Palestinian Authority.
AB  - BACKGROUND: Exposure to ongoing political violence and stressful conditions
      increases the risk of posttraumatic stress disorder (PTSD) in low-resource
      contexts. However, much of our understanding of the determinants of PTSD in these
      contexts comes from cross-sectional data. Longitudinal studies that examine
      factors associated with incident PTSD may be useful to the development of
      effective prevention interventions and the identification of those who may be
      most at-risk for the disorder. METHODS: A 3-stage cluster random stratified
      sampling methodology was used to obtain a representative sample of 1,196
      Palestinian adults living in Gaza, the West Bank and East Jerusalem. Face-to-face
      interviews were conducted at two time points 6-months apart. Logistic regression
      analyses were conducted on a restricted sample of 643 people who did not have
      PTSD at baseline and who completed both interviews. RESULTS: The incidence of
      PTSD was 15.0 % over a 6-month period. Results of adjusted logistic regression
      models demonstrated that talking to friends and family about political
      circumstances (aOR = 0.78, p = 0.01) was protective, and female sex (aOR = 1.76,
      p = 0.025), threat perception of future violence (aOR = 1.50, p = 0.002), poor
      general health (aOR = 1.39, p = 0.005), exposure to media (aOR = 1.37, p =
      0.002), and loss of social resources (aOR = 1.71, p = 0.006) were predictive of
      incident cases of PTSD. CONCLUSIONS: A high incidence of PTSD was documented
      during a 6-month follow-up period among Palestinian residents of Gaza, the West
      Bank, and East Jerusalem. Interventions that promote health and increase and
      forestall loss to social resources could potentially reduce the onset of PTSD in
      communities affected by violence.

PMID- 25398201
TI  - Imaging transient formation of diffusion layers with fluorescence-enabled
      electrochemical microscopy.
AB  - Fluorescence-enabled electrochemical microscopy (FEEM) is demonstrated as a new
      technique to image transient concentration profiles of redox species generated on
      ultramicroelectrodes (UMEs). FEEM converts an electrical signal into an optical
      signal by electrically coupling a conventional redox reaction to a fluorogenic
      reporter reaction on a closed bipolar electrode. We describe the implementation
      of FEEM for diffusion layer imaging and use an array of thousands of parallel
      bipolar electrodes to image the diffusion layers of UMEs in two and three
      dimensions. This new technique provides a way to image an entire 2-dimensional
      lateral cross section of a dynamic diffusion layer in a single experiment. By
      taking several of these lateral cross sections at different axial positions in
      the diffusion layer, a 3-dimensional image of the diffusion layer can be built.
      We image the diffusion layer of a 10 MUm diameter carbon fiber electrode over the
      course of a cyclic voltammetry experiment and compare the FEEM-generated images
      to concentration profiles generated from numerical simulation. We also image the
      diffusion layer of a two electrode array consisting of two 10 MUm diameter carbon
      fibers over the course of a potential step experiment. 

PMID- 25398200
TI  - Novel insights into host-fungal pathogen interactions derived from live-cell
      imaging.
AB  - The theoretical physicist and Nobel laureate Richard Feynman outlined in his 1959
      lecture, "There's plenty of room at the bottom", the enormous possibility of
      producing and visualising things at smaller scales. The advent of advanced
      scanning and transmission electron microscopy and high-resolution microscopy has
      begun to open the door to visualise host-pathogen interactions at smaller scales,
      and spinning disc confocal and two-photon microscopy has improved our ability to
      study these events in real time in three dimensions. The aim of this review is to
      illustrate some of the advances in understanding host-fungal interactions that
      have been made in recent years in particular those relating to the interactions
      of live fungal pathogens with phagocytes. Dynamic imaging of host-pathogen
      interactions has recently revealed novel detail and unsuspected mechanistic
      insights, facilitating the dissection of the phagocytic process into its
      component parts. Here, we will highlight advances in our knowledge of host-fungal
      pathogen interactions, including the specific effects of fungal cell viability,
      cell wall composition and morphogenesis on the phagocytic process and try to
      define the relative contributions of neutrophils and macrophages to the clearance
      of fungal pathogens in vitro and the infected host. 

PMID- 25398202
TI  - Metabolic and glycemic sequelae of sleep disturbances in children and adults.
AB  - The prevalence of obesity in adults and children has increased greatly in the
      past three decades, as have metabolic sequelae, such as insulin resistance and
      type 2 diabetes mellitus (T2DM). Sleep disturbances are increasingly recognized
      as contributors to this widespread epidemic in adults, and data are emerging in
      children as well. The categories of sleep disturbances that contribute to obesity
      and its glycemic co-morbidities include the following: (1) alterations of sleep
      duration, chronic sleep restriction and excessive sleep; (2) alterations in sleep
      architecture; (3) sleep fragmentation; (4) circadian rhythm disorders and
      disruption (i.e., shift work); and (5) obstructive sleep apnea. This article
      reviews current evidence supporting the contributions that these sleep disorders
      play in the development of obesity, insulin resistance, and T2DM as well as
      possibly influences on glycemic control in type 1 diabetes, with a special focus
      on data in pediatric populations. 

PMID- 25398203
TI  - PCOS in adolescence and type 2 diabetes.
AB  - Polycystic ovary syndrome is a frequent disorder in women of reproductive age
      that consists of a heterogeneous combination of hyperandrogenism, chronic
      anovulation, and polycystic ovaries. Hyperandrogenism and anovulation are clearly
      linked to insulin resistance and compensatory hyperinsulinism, with an ovarian
      androgenic hyperresponsiveness to circulating insulin. Evidence is increasing
      that suggests that lipotoxicity, which is a key mechanism in the development of
      insulin resistance and type 2 diabetes, could also explain the androgen
      overproduction. During adolescence, diagnosis of polycystic ovarian syndrome
      (PCOS) may be difficult but is of importance because PCOS increases future risk
      of type 2 diabetes and metabolic complications. Metabolic perturbations begin
      early in adolescence and also exist in adolescent relatives of women with PCOS,
      even before clinical signs of PCOS. Screening for impaired glucose tolerance or
      type 2 diabetes is also important in this population, and treatment should focus
      on PCOS clinical manifestations as well as long-term metabolic risk. 

PMID- 25398204
TI  - Glycemic targets in pregnancies affected by diabetes: historical perspective and
      future directions.
AB  - The definition of optimal glycemic control in pregnancies affected by diabetes
      remains enigmatic. Diabetes phenotypes are heterogeneous. Moreover, fetal
      macrosomia insidiously occurs even with excellent glycemic control. Current blood
      glucose (BG) targets (FBG <=95, 1-h post-prandial <140, 2 h <120 mg/dL) have
      improved perinatal outcomes, but arguably they have not normalized. The
      conventional management approach has been to replicate a pattern of glycemia in
      normal pregnancy. Although these patterns are lower than previously appreciated,
      a randomized controlled trial (RCT) has never compared current vs. lower glucose
      targets powered on maternal/fetal outcomes. This paper provides historical
      context to the current targets by reviewing evidence supporting their evolution.
      Using lower targets (FBG <90, 1 h <122, 2 h <110, mean BG <=95 mg/dL) may help
      normalize outcomes, but phenotypic differences (type 1 vs. type 2 vs. gestational
      diabetes) might require different glycemic goals. There remains a critical need
      for well-designed RCTs to confirm optimal glycemic control that minimizes both
      small for and large for gestational age across pregnancies affected by diabetes.

PMID- 25398205
TI  - Morbidity and mortality in young-onset type 2 diabetes in comparison to type 1
      diabetes: where are we now?
AB  - Increasingly, we recognise that type 2 diabetes in youth is a disease with an
      aggressive time course and a significant complication risk. On the other hand,
      outcomes for youth with type 1 diabetes appear generally to be improving. With
      increasing numbers of both types of diabetes in youth, it is timely that a
      comparative perspective is offered to help clinicians prognosticate more
      appropriately. Contemporary comparative studies add a new perspective to a
      consistent story, that for youth-onset type 2 diabetes, the development and
      progression of cardio-renal complications are increased and the survival
      prognosis is significantly worse than for type 1 diabetes. Here, we review this
      mounting evidence, highlight the importance of metabolic syndrome factors in the
      excess risk and underscore that there remains a significant mortality gap for
      youth with either type of diabetes, to be addressed as a matter of urgency. 

PMID- 25398206
TI  - Probiotics and pregnancy.
AB  - Complications of pregnancy are associated with adverse outcomes for mother and
      baby in the short and long term. The gut microbiome has been identified as a key
      factor for maintaining health outside of pregnancy and could contribute to
      pregnancy complications. In addition, the vaginal and the recently revealed
      placental microbiome are altered in pregnancy and may play a role in pregnancy
      complications. Probiotic supplementation could help to regulate the unbalanced
      microflora composition observed in obesity and diabetes. Here, the impact of
      probiotic supplementation during pregnancy and infancy is reviewed. There are
      indications for a protective role in preeclampsia, gestational diabetes mellitus,
      vaginal infections, maternal and infant weight gain and allergic diseases. Large,
      well-designed randomised controlled clinical trials along with metagenomic
      analysis are needed to establish the role of probiotics in adverse pregnancy and
      infancy outcomes. 

PMID- 25398208
TI  - Lighter: fast and memory-efficient sequencing  error correction without counting.
AB  - Lighter is a fast, memory-efficient tool for correcting sequencing errors.
      Lighter avoids counting k-mers. Instead, it uses a pair of Bloom filters, one
      holding a sample of the input k-mers and the other holding k-mers likely to be
      correct. As long as the sampling fraction is adjusted in inverse proportion to
      the depth of sequencing, Bloom filter size can be held constant while maintaining
      near-constant accuracy. Lighter is parallelized, uses no secondary storage, and
      is both faster and more memory-efficient than competing approaches while
      achieving comparable accuracy.

PMID- 25398207
TI  - Lifestyle therapy for the treatment of youth with type 2 diabetes.
AB  - Type 2 diabetes (T2D) in youth is a relatively novel condition facing paediatric
      health care providers. Few experimental trials exist to guide clinical management
      in this population. Supporting and prescribing modifiable lifestyle behaviours is
      cornerstone in the management of T2D in adults. Clinical trials in obese
      adolescents suggest that intensive lifestyle interventions that include both
      dietary changes and increased physical activity elicit clinically meaningful
      reductions in weight and improve cardiovascular risk profiles. Observational
      studies in youth with T2D suggest that better diet quality and increased physical
      activity are associated with better metabolic control; however, the limited
      experimental data available does not support these observations. Trials
      evaluating lifestyle monotherapy for the treatment of hyperglycaemia in youth
      with T2D do not exist, and the only study evaluating combined lifestyle and
      pharmacologic therapy did not show additional benefit over pharmacologic
      treatment with metformin alone. Physiological and psychosocial differences
      between youth and adults with T2D likely contribute to the differences in the
      effectiveness of lifestyle therapy for improving glycaemic control. The current
      review describes these topics in detail and provides recommendations for
      paediatric health care providers for the promotion of lifestyle therapy for the
      management of hyperglycaemia and cardiovascular risk factors for youth with T2DM.

PMID- 25398209
TI  - Validity of bioelectrical impedance measurement in predicting fat-free mass of
      Chinese children and adolescents.
AB  - BACKGROUND: The current study aimed to examine the validity of various published
      bioelectrical impedance analysis (BIA) equations in estimating FFM among Chinese
      children and adolescents and to develop BIA equations for the estimation of fat
      free mass (FFM) appropriate for Chinese children and adolescents.
      MATERIAL/METHODS: A total of 255 healthy Chinese children and adolescents aged 9
      to 19 years old (127 males and 128 females) from Tianjin, China, participated in
      the BIA measurement at 50 kHz between the hand and the foot. The criterion
      measure of FFM was also employed using dual-energy X-ray absorptiometry (DEXA).
      FFM estimated from 24 published BIA equations was cross-validated against the
      criterion measure from DEXA. Multiple linear regression was conducted to examine
      alternative BIA equation for the studied population. RESULTS: FFM estimated from
      the 24 published BIA equations yielded high correlations with the directly
      measured FFM from DEXA. However, none of the 24 equations was statistically
      equivalent with the DEXA-measured FFM. Using multiple linear regression and cross
      validation against DEXA measurement, an alternative prediction equation was
      determined as follows: FFM (kg)=1.613+0.742*height (cm)2/impedance
      (Omega)+0.151*body weight (kg); R2=0.95; SEE=2.45 kg; CV=6.5, 93.7% of the
      residuals of all the participants fell within the 95% limits of agreement.
      CONCLUSIONS: BIA was highly correlated with FFM in Chinese children and
      adolescents. When the new developed BIA equations are applied, BIA can provide a
      practical and valid measurement of body composition in Chinese children and
      adolescents.

PMID- 25398210
TI  - Predictors of ectopic firing from the superior vena cava in patients with
      paroxysmal atrial fibrillation.
AB  - PURPOSE: Although catheter ablation targeting the pulmonary vein (PV) is a well
      known therapy for patients with paroxysmal atrial fibrillation (PAF), ectopic
      firings from the superior vena cava (SVC) can initiate PAF. The purpose of this
      study was to investigate predictors of SVC firing. METHODS: The subjects included
      336 consecutive PAF patients (278 males, age 56.1 +/- 10.8 years) undergoing
      atrial fibrillation (AF) ablation. The appearance of SVC firing was monitored
      throughout the procedure using a decapolar catheter with multiple electrodes to
      record electrograms of the coronary sinus and SVC. In addition to PV isolation,
      SVC isolation was performed only in patients with documented SVC firing. RESULTS:
      SVC firing was observed in 43/336 (12.8 %) of the patients, among whom complete
      isolation of the SVC was achieved in 40/43 (93 %) patients. A lower body mass
      index (BMI) (22.8 +/- 2.8 vs 24.1 +/- 3.1 kg/m(2), p = 0.007) and higher
      prevalence of prior ablation procedures (58 vs 18 %, p = 0.0001) were related to
      the presence of SVC firing. In a multivariate analysis, a lower BMI (p = 0.012;
      odds ratio 0.83, 95 % CI 0.72 to 0.96) and history of prior ablation procedures
      (p < 0.0001; odds ratio 5.37, 95 % CI 2.71 to 10.63) were found to be independent
      predictors of the occurrence of SVC firing. Among 96 patients undergoing repeat
      ablation procedures, less PV-left atrial re-conduction was observed in patients
      with SVC firing than in those without (2.7 +/- 1.2 vs 3.2 +/- 0.8, p = 0.02).
      CONCLUSIONS: The presence of SVC firing in patients with PAF is associated with a
      history of repeat ablation procedures and lower BMI values.

PMID- 25398211
TI  - Spatial and temporal distribution of incidence of acquired equine polyneuropathy
      in Norway and Sweden, 1995-2012.
AB  - BACKGROUND: Acquired equine polyneuropathy (AEP) is an emerging disease in horses
      in Sweden, Norway and Finland since 1995. Affected horses show bilateral pelvic
      limb knuckling and weakness, sometimes progressing to recumbency and euthanasia.
      The aetiology is unknown but is thought to be non-infectious and non-genetic,
      though possibly toxic or toxico-infectious. The objectives of this study were to
      describe the spatial, temporal and spatio-temporal features of AEP in Norway and
      Sweden for the period of 1995 to 2012. Data from all documented case farms (n =
      136) were used. Space-time interaction clustering of case farms was investigated
      with a retrospective space-time scan statistic with a space-time permutation
      model, the space-time K-function and the Jacquez k nearest neighbour (kNN) test.
      RESULTS: There was a clear seasonality in disease occurrence, as 123 case farms
      presented their first case from January to May. However, there was large
      variation in the number of case farms between years. Case farms were more
      numerous in certain regions. Despite the larger horse population in Sweden, 120
      of the case farms were in Norway. Space-time clustering was supported by the K
      function and partly by the space-time scan, but not by the Jacquez k nearest
      neighbour (kNN) test. CONCLUSIONS: The results suggest an aetiology for AEP where
      the exposure is not consistent in time, but varies during and between years,
      assuming that the incubation period does not vary greatly. The results further
      suggest that the exposure varies between regions as well. Two out of three
      different analytical methods supported spatio-temporal clustering of case farms,
      which rendered inconclusive results. The negative result in the kNN test might be
      explained by lack of power, which is due to the small number of outbreaks in
      relation to the size of the study area and length of the study period, and
      further by the low to moderate power of methods to detect space-time clustering
      when the background population is unknown. Further research is needed to study
      how management, meteorological variables and other factors with local or regional
      differences may explain outbreaks of AEP.

PMID- 25398212
TI  - Genetic polymorphisms of the organic cation transporter 1 gene (SLC22A1) within
      the Cape Admixed population of South Africa.
AB  - Human organic cation transporter 1 (hOCT1) is expressed primarily in hepatocytes
      and mediate the electrogenic transport of various endogenous and exogenous
      compounds, including clinically important drugs. Genetic polymorphisms in the
      gene coding for hOCT1, SLC22A1, are increasingly being recognized as a possible
      mechanism explaining the variable response of individual patients to clinical
      drugs which are substrates for this transporter. The aim of this study was to
      investigate the allele and genotype frequencies of single-nucleotide
      polymorphisms (SNPs) of SLC22A1 in the Cape Admixed population of South Africa.
      The genotypic and allelic distributions of nineteen nonsynonomous and one
      intronic SLC22A1 SNPs were determined in 100 healthy Cape Admixed participants,
      using a SNaPshot((r)) multiplex assay. In addition, haplotype structure for
      SLC22A1 was inferred from the genotypic data. The minor allele frequencies for
      S14F, P341L, S189L, G220V, V519F, M440I, G465R and the rs622342 intronic variant
      were 1.0, 0.5, 1.0, 1.0, 1.5, 0.5, 0.5 and 18.0%, respectively. None of the
      participants carried the variant allele for R61C, C88R, P283L, R287G and G401S.
      In addition, no variant alleles were observed for A306T, A413V, M420V, I421F,
      C436F, V501E, and I542V in the population. Twelve haplotypes were inferred from
      the genotypic data. The frequencies for most common haplotypes
      CCTCGGCGCGCTAGAGCTGA, CCTCGGCGCGCTAGCGCTGA and CCTCGGCGCGCGAGCGCTGA were 80, 9.9,
      and 3.5%, respectively.

PMID- 25398213
TI  - Molecular characterisation and expression analysis of a novel calreticulin (CRT)
      gene in the dinoflagellate Prorocentrum minimum.
AB  - Calreticulin is a multifunctional Ca(2+)-binding protein that has been well
      characterised in mammalian cells. Here, we characterised a novel calreticulin
      (CRT2) gene in the dinoflagellate Prorocentrum minimum, which codes for a calcium
      binding protein and examined its expression pattern following the addition of
      calcium and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid
      (EGTA). PmCRT2 is encoded in the nuclear genome of P. minimum without introns.
      The full length cDNA of PmCRT2 was found to be 1,493 base pairs (bp) in length,
      which ranges from the dinoflagellate spliced leader sequence to the poly (A) tail
      and contains a 1,173-bp open reading frame, a 70-bp 5'-untranslated region (UTR),
      and a 207-bp 3'-UTR. On the basis of in silico analyses that revealed the
      distinct domain architectures of PmCRT2, we classified this protein under the
      calreticulin family. PmCRT2 gene expression was up-regulated in the presence of
      excess calcium in a dose-dependent manner; however, PmCRT2 expression was down
      regulated by the addition of EGTA. These results clearly indicate that PmCRT2
      plays a vital role in calcium regulation and this may be involved in the stress
      response of P. minimum. 

PMID- 25398214
TI  - Association between ABCG1 polymorphism rs1893590 and high-density lipoprotein
      (HDL) in an asymptomatic Brazilian population.
AB  - ATP binding cassette transporter G1 (ABCG1) promotes lipidation of nascent high
      density lipoprotein (HDL) particles, acting as an intracellular transporter. SNP
      rs1893590 (c.-204A > C) of ABCG1 gene has been previously studied and reported as
      functional over plasma HDL-C and lipoprotein lipase activity. This study aimed to
      investigate the relationships of SNP rs1893590 with plasma lipids and
      lipoproteins in a large Brazilian population. Were selected 654 asymptomatic and
      normolipidemic volunteers from both genders. Clinical and anthropometrical data
      were taken and blood samples were drawn after 12 h fasting. Plasma lipids and
      lipoproteins, as well as HDL particle size and volume were determined. Genomic
      DNA was isolated for SNP rs1893590 detection by TaqMan((r)) OpenArray((r)) Real
      Time PCR Plataform (Applied Biosystems). Mann-Whitney U, Chi square and two-way
      ANOVA were the used statistical tests. No significant differences were found in
      the comparison analyses between the allele groups for all studied parameters.
      Conversely, significant interactions were observed between SNP and age over
      plasma HDL-C, were volunteers under 60 years with AA genotype had increased HDL-C
      (p = 0.048). Similar results were observed in the group with body mass index
      (BMI) < 25 kg/m(2), where volunteers with AA genotype had higher HDL-C levels (p
      = 0.0034), plus an increased HDL particle size (p = 0.01). These findings
      indicate that SNP rs1893590 of ABCG1 has a significant impact over HDL-C under
      asymptomatic clinical conditions in an age and BMI dependent way. 

PMID- 25398215
TI  - Effect of salinity stress on plants and its tolerance strategies: a review.
AB  - The environmental stress is a major area of scientific concern because it
      constraints plant as well as crop productivity. This situation has been further
      worsened by anthropogenic activities. Therefore, there is a much scientific
      saddle on researchers to enhance crop productivity under environmental stress in
      order to cope with the increasing food demands. The abiotic stresses such as
      salinity, drought, cold, and heat negatively influence the survival, biomass
      production and yield of staple food crops. According to an estimate of FAO, over
      6% of the world's land is affected by salinity. Thus, salinity stress appears to
      be a major constraint to plant and crop productivity. Here, we review our
      understanding of salinity impact on various aspects of plant metabolism and its
      tolerance strategies in plants.

PMID- 25398217
TI  - Influence of soil mercury concentration and fraction on bioaccumulation process
      of inorganic mercury and methylmercury in rice (Oryza sativa L.).
AB  - Recent studies showed that rice is the major pathway for methylmercury (MeHg)
      exposure to inhabitants in mercury (Hg) mining areas in China. There is,
      therefore, a concern regarding accumulation of Hg in rice grown in soils with
      high Hg concentrations. A soil pot experimental study was conducted to
      investigate the effects of Hg-contaminated soil on the growth of rice and uptake
      and speciation of Hg in the rice. Our results imply that the growth of rice
      promotes residual fraction of Hg transforming to organic-bound fraction in soil
      and increased the potential risks of MeHg production. Bioaccumulation factors
      deceased for IHg but relatively stabilized for MeHg with soil total mercury (THg)
      increasing. IHg in soil was the major source of Hg in the root and stalk, but
      leaf was contributed by Hg from both atmosphere and soil. Soluble and
      exchangeable Hg fraction can predict the bioavailability of IHg and MeHg in
      soils, and that can provide quantitative description of the rate of uptake of the
      bioavailable Hg. Soluble and exchangeable Hg fraction in paddy soil exceeding
      0.0087 mg kg(-1) may cause THg concentration in rice grain above the permissible
      limit standard, and MeHg concentration in paddy soil more than 0.0091 mg kg(-1)
      may have the health risks to humans.

PMID- 25398216
TI  - Changes in protein expression of pacific oyster Crassostrea gigas exposed in situ
      to urban sewage.
AB  - The composition and concentration of substances in urban effluents are complex
      and difficult to measure. These contaminants elicit biological responses in the
      exposed organisms. Proteomic analysis is a powerful tool in environmental
      toxicology by evidencing alterations in protein expression due to exposure to
      contaminants and by providing a useful framework for the development of new
      potential biomarkers. The aim of this study was to determine changes in protein
      expression signatures (PES) in the digestive gland of oysters Crassostrea gigas
      transplanted to two farming areas (LIS and RIB) and to one area contaminated by
      sanitary sewage (BUC) after 14 days of exposure. This species is one of the most
      cultivated molluscs in the world. The identified proteins are related to the
      cytoskeleton (CKAP5 and ACT2), ubiquitination pathway conjugation (UBE3C), G
      protein-coupled receptor and signal transduction (SVEP1), and cell cycle/division
      (CCNB3). CKAP5 showed higher expression in oysters kept at BUC in comparison with
      those kept at the farming areas, while ACT2, UBE3C, SVEP1, and CCNB3 were
      suppressed. The results suggest that these changes might lead to DNA damage,
      apoptosis, and interference with the immune system in oyster C. gigas exposed to
      sewage and give initial information on PES of C. gigas exposed to sanitary
      sewage, which can subsequently be useful in the development of more sensitive
      tools for biomonitoring coastal areas, particularly those devoted mainly to
      oyster farming activities.

PMID- 25398218
TI  - Antioxidant status and Na(+), K (+)-ATPase activity in freshwater fish Carassius
      auratus exposed to different combustion products of Nafion 117 membrane: an
      integrated biomarker approach.
AB  - Nafion 117 membrane (N117), an important polymer electrolyte membrane (PEM), has
      been widely applied in numerous chemical technologies. Its increasing production
      and utilization will inevitably lead to the problem of waste disposal, with
      incineration as an important method. However, toxicity data of its combustion
      products on aquatic organisms have been seldom reported. The present study was
      therefore conducted to investigate the antioxidant response and Na(+), K(+)
      ATPase activity in liver of Carassius auratus exposed to different combustion
      products of N117 for 5, 15, and 30 days. The concentrations of fluorine ion (F(
      )) in the aquaria among the exposure durations were analyzed using the ion
      chromatography system. The results showed that these treatments have the
      capability to induce oxidative stress and suppress Na(+), K(+)-ATPase activity,
      as indicated by some significant alterations on these measured toxicity end
      points in fish liver. According to the integrated biomarker response (IBR) index,
      the toxicity intensity of these experimental treatments was tentatively ranked.
      Taken together, these observations provided some preliminary data on the
      potential toxicity of the combustion products of N117 on aquatic organisms and
      could fill the information gaps in the toxicity database of the current-use PEM.

PMID- 25398219
TI  - Meta-analysis of tumor necrosis factor alpha -308 polymorphism and knee
      osteoarthritis risk.
AB  - BACKGROUND: Several case-control studies have been conducted to clarify the
      association between the tumor necrosis factor alpha (TNF-alpha) -G308A
      polymorphism and risk of osteoarthritis (OA); however, the results are
      inconsistent. This meta-analysis was performed to clarify this issue using all
      the available evidence. METHODS: Eligible articles were retrieved by searching
      PubMed, Web of science and Google scholar. The strength of the association
      between the TNF-alpha -G308A polymorphism and risk of OA was assessed by odds
      ratios (ORs) with the corresponding 95% confidence interval (CI) for each study.
      RESULTS: Seven studies were included in the meta-analysis, which included 983 OA
      cases and 1355 controls. The pooled analysis based on all included studies showed
      a significantly increased OA risk in the recessive genetic model analysis (OR =
      11.08, 95% CI = 4.75-25.86, p < 0.001) and in the A allele vs. G allele analysis
      (OR = 2.30, 95% CI = 1.08-4.90). However, there was no statistical difference in
      the dominant genetic model analysis (OR = 2.45, 95% CI = 0.95-6.27, p = 0.06).
      Furthermore, we found that OA patients had a higher frequency of the AA genotype
      (OR = 10.49, 95% CI = 4.47-24.61) and GA genotype (OR = 1.78, 95% CI = 1.03-3.08)
      compared with the control population. CONCLUSION: Our results suggested that the
      TNF-alpha -G308A polymorphism were associated with an increased risk of OA.

PMID- 25398220
TI  - Management of Hypoxic-ischemic Encephalopathy.

PMID- 25398221
TI  - Impact of implementation of NRHM program on NMR in Tamil Nadu (TN): a case study.
AB  - The Government of India had set up the National Rural Health Mission (NRHM) in
      2005 in an effort towards providing quality healthcare to the underserved rural
      areas and also to achieve the Millennium Development Goals (MDGs) by 2015. While
      the trends in child and maternal mortality show great progress by India since
      1990 with steady decline in Maternal Mortality Ratio (MMR) and Infant Mortality
      Rate (IMR), a comparison of the predicted trend and target of MDGs show that
      India would fall short by a few points. In contrast, Tamil Nadu has reached its
      MDGs and is ensuring sustained progress in reducing child and maternal mortality
      with an effective implementation of the various schemes of NRHM. Tamil Nadu leads
      the way in ensuring universal health coverage leveraging the expertise and funds
      of NRHM by providing round the clock services, introducing new and innovative
      programs to improve outcomes and regular monitoring of the functional operation
      and outcomes to ensure effective implementation. Adopting the features of the
      Tamil Nadu model of healthcare system that caters to their particular state and
      effectively implementing the initiatives of NRHM would help the other states in
      considerably reducing the child and maternal mortality and also ensure early
      achievement of MDGs by the nation. 

PMID- 25398222
TI  - A critical comparison of different approaches to sediment-quality assessments in
      the Santos Estuarine System in Brazil.
AB  - This study focuses on the discussion of different lines of evidence (LoEs)
      applied to a sediment-quality assessment that considered the following: chemical
      concentrations of metals; polycyclic aromatic hydrocarbons (PAHs) in estuarine
      waters, sediments, and oysters (native and caged Crassostrea brasiliana); PAHs in
      semipermeable membrane devices (SPMDs); simultaneously extracted metals-acid
      volatile sulfides (SEM-AVS); benthic community assessment (the exploratory
      benthic index and the relative benthic index); chronic toxicity tests with the
      sea urchin Lytechinus variegatus; and bioaccumulation models. Significantly
      contaminated sediments from the Santos Estuarine System and the consequent
      toxicity of tested organisms were measured. Caged oysters presented
      bioaccumulation rates <=2,500% of total PAH content and 200% of metal content
      when compared with control organisms from an uncontaminated area. SPMD results
      presented the same bioaccumulation pattern as caged oysters but at lower
      concentrations. Benthic communities presented some alterations, and there was a
      predominance of tolerant species in the inner part of the estuary. According to
      the SEM-AVS approach, metals should be assumed to be nonbioavailable, but
      experiments with transplanted C. brasiliana showed metal bioaccumulation,
      particularly in the cases of chromium, copper, mercury, and zinc. The weight-of
      evidence approach was applied to compare and harmonize LoEs commonly used in
      sediment-quality assessments and to then classify estuary environments according
      to both their potential for having adverse effects on the biota and their
      possible ecological risks. All of the results of these approaches (except for SEM
      AVS) were found to complement each other.

PMID- 25398223
TI  - Transglutaminase 2 and neuroinflammation.
AB  - Neuroinflammatory processes seem to play a pivotal role in various chronic
      neurodegenerative diseases, characterized also by the pathogenetic accumulation
      of specific protein aggregates. Several of these proteins have been shown to be
      substrates of transglutaminases, calcium-dependent enzymes that catalyze protein
      crosslinking reactions. However, it has recently been demonstrated that
      transglutaminase 2 (TG2) may also be involved in molecular mechanisms underlying
      inflammation. In the central nervous system, astrocytes and microglia are the
      cell types mainly involved in the inflammatory process. This review is focused on
      the increases of TG2 protein expression and enzyme activity that occur in
      astroglial, microglial and monocyte cell models in response to inflammatory
      stimuli. The transcription factor NF-kappaB is considered the main regulator of
      inflammation, being activated by a variety of stimuli including calcium influx,
      oxidative stress and inflammatory cytokines. Under these conditions, the over
      expression of TG2 results in the sustained activation of NF-kappaB. Several
      findings emphasize the possible role of the TG2/NF-kappaB activation pathway in
      neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease,
      multiple sclerosis and amyotrophic lateral sclerosis. Although further studies
      are needed to characterize the TG2/NF-kappaB cross-talk in
      monocytes/macrophages/microglia within the central nervous system, some results
      show that TG2 and NF-kappaB are co-localized in cell compartments. Together,
      evidence suggests that TG2 plays a role in neuroinflammation and contributes to
      the production of compounds that are potentially deleterious to neuronal cells. 

PMID- 25398226
TI  - Locum doctor is struck off for misconduct and continued denial of wrongdoing.

PMID- 25398225
TI  - Acute exercise and gastric emptying: a meta-analysis and implications for
      appetite control.
AB  - BACKGROUND: Gastric emptying (GE) could influence exercise-induced changes in
      appetite and energy intake. GE also could contribute to changes in gastric
      symptoms and the availability of nutrients during exercise, which will
      subsequently affect performance. OBJECTIVE: The objective of this review was to
      determine the effects of acute exercise on GE using a systematic review and meta
      analysis. The most common parameters to determine GE were selected, consisting of
      half-emptying time and volume emptied. Oral-caecal transit time (OCTT) was also
      examined. DATA SOURCES: Research databases (PubMed, Scopus, Google Scholar,
      EBSCOhost, SPORTDiscus) were searched through November 2013 for original studies,
      abstracts, theses and dissertations that examined the influence of acute exercise
      on GE. STUDY SELECTION: Studies were included if they evaluated GE or OCTT during
      and/or after exercise and involved a resting control trial. STUDY APPRAISAL AND
      SYNTHESIS: Initially, 195 studies were identified. After evaluation of study
      characteristics and quality and validity, data from 20 studies (35 trials)
      involving 221 participants (157 men; 52 women; 12 unknown) were extracted for
      meta-analysis. Random-effects meta-analyses were utilised for the three main
      outcome variables, and effect sizes (ES) are reported as Hedge's g due to
      numerous small sample sizes. RESULTS: Random-effects modelling revealed non
      significant and small/null main effect sizes for volume emptied (ES = 0.195; 95%
      CI -0.25 to 0.64), half-time (ES = -0.109, 95% CI -0.66 to 0.44) and OCTT (ES =
      0.089; 95% CI -0.64 to 0.82). All analyses exhibited significant heterogeneity
      and numerous variables moderated the results. There was a dose response of
      exercise intensity; at lower intensities GE was faster, and at high exercise
      intensities GE was slower. Walking was associated with faster GE and cycling with
      slower GE. Greater volume of meal/fluid ingested, higher osmolality of beverage
      and longer exercise duration were also associated with slower GE with exercise.
      LIMITATIONS: The major limitation is that the majority of studies utilised a
      liquid bolus administered pre-exercise to determine GE; the relationship to post
      exercise appetite and energy intake remains unknown. Study populations were also
      generally active or trained individuals. Furthermore, our review was limited to
      English language studies and studies that utilised resting control conditions.
      CONCLUSIONS: These results suggest that exercise intensity, mode, duration and
      the nature of meal/fluid ingested all influence GE during and after acute
      exercise. The relationship of GE parameters with appetite regulation after
      exercise remains largely unexplored. Further integrative studies combining GE and
      alterations in gut hormones, as well as in populations such as overweight and
      obese individuals are needed.

PMID- 25398224
TI  - The role of oxidative, inflammatory and neuroendocrinological systems during
      exercise stress in athletes: implications of antioxidant supplementation on
      physiological adaptation during intensified physical training.
AB  - During periods of intensified physical training, reactive oxygen species (ROS)
      release may exceed the protective capacity of the antioxidant system and lead to
      dysregulation within the inflammatory and neuroendocrinological systems.
      Consequently, the efficacy of exogenous antioxidant supplementation to maintain
      the oxidative balance in states of exercise stress has been widely investigated.
      The aim of this review was to (1) collate the findings of prior research on the
      effect of intensive physical training on oxidant-antioxidant balance; (2)
      summarise the influence of antioxidant supplementation on the reduction-oxidation
      signalling pathways involved in physiological adaptation; and (3) provide a
      synopsis on the interactions between the oxidative, inflammatory and
      neuroendocrinological response to exercise stimuli. Based on prior research, it
      is evident that ROS are an underlying aetiology in the adaptive process; however,
      the impact of antioxidant supplementation on physiological adaptation remains
      unclear. Equivocal results have been reported on the impact of antioxidant
      supplementation on exercise-induced gene expression. Further research is required
      to establish whether the interference of antioxidant supplementation consistently
      observed in animal-based and in vivo research extends to a practical sports
      setting. Moreover, the varied results reported within the literature may be due
      to the hormetic response of oxidative, inflammatory and neuroendocrinological
      systems to an exercise stimulus. The collective findings suggest that intensified
      physical training places substantial stress on the body, which can manifest as an
      adaptive or maladaptive physiological response. Additional research is required
      to determine the efficacy of antioxidant supplementation to minimise exercise
      stress during intensive training and promote an adaptive state. 

PMID- 25398227
TI  - Aspirin-induced increase in intestinal paracellular permeability does not affect
      the levels of LPS in venous blood of healthy women.
AB  - The presence of subclinical levels of LPS from Gram-negative bacteria, also
      referred to as endotoxin, in the circulation may induce a pro-inflammatory immune
      response that leads to the development of obesity and insulin resistance. Recent
      data indicate that high-fat meals may elevate circulating levels of LPS. However,
      it is currently unclear how the LPS transits from the gut lumen to the general
      circulation. We determined whether aspirin-induced damage of the small intestinal
      mucosa, evidenced by an increase in the paracellular permeability, allows greater
      transit of LPS into the systemic circulation. The 3-h cumulative excretion of
      lactulose was significantly increased after the consumption of aspirin solution
      relative to that after the consumption of an equal volume of water in 15 healthy
      women (median after aspirin 0.09% of dose vs. median after water 0.03% of dose; P
      = 0.004). Dosage with aspirin also significantly increased the lactulose :
      mannitol ratio (median after aspirin 0.014 vs. median after water 0.005; P =
      0.017). However, serum LPS levels after the consumption of the aspirin solution
      were not significantly different from those after consumption of the control
      (plain water). Further, there was no correlation between body fat content and
      circulating levels of LPS.

PMID- 25398228
TI  - Incidence and clinical significance of iliac vein compression.
AB  - OBJECTIVES: To determine the frequency of left common iliac vein (CIV)
      compression by the right common iliac artery (CIA) based on CT scan images.
      METHODS: CT scan images were reviewed and the diameter of CIV was measured at the
      area of minimal diameter and compared to the distal adjacent segment and the
      contralateral CIV at the same level. Medical records were reviewed for symptoms,
      deep vein thrombosis (DVT) and risk factors that might be associated with DVT.
      Data were analyzed with SPSS program using both Chi square and t test. A p < 0.05
      was considered statistically significant. Linear regression (R2) was used to
      evaluate correlation. RESULTS: A total of 300 complete records were reviewed. The
      mean age was 51.89 years, with 126 (42%) males. Comparison between the two groups
      (>70% vs <70%) showed similar clinical factors such as history of DVT, surgery,
      immobilization, malignancy, limb trauma, pregnancy, obesity, CHF, and smoking.
      There were more females with CIV compression of 70% or more than males (19.5% vs
      11.1% P < .049). CONCLUSION: Diameter stenosis more than 70% was present in 30.6%
      of cases with higher incidence in females. The presence of stenosis was not
      associated with the presence of clinical symptoms.

PMID- 25398230
TI  - The Next Step: A Common Neural Mechanism for Freezing of Gait.
AB  - Freezing of gait is a disabling symptom of Parkinson's disease that causes a
      paroxysmal cessation of normal footsteps while walking. Despite a great deal of
      empirical research, the pathophysiological mechanisms underlying the symptom
      remain unclear. In this targeted review, we synthesize recent insights from
      research into freezing in an effort to clarify the neurobiological basis of this
      phenomenon. We conclude that freezing manifests via a common neural pathway in
      which transient increases in inhibitory basal ganglia output lead to decreased
      activity within the brainstem structures that coordinate gait. This cascade may
      be triggered through dopaminergic depletion in the striatum and over-activity
      within the subthalamic nucleus. These insights may benefit both the diagnostic
      and therapeutic management of freezing in Parkinson's disease. 

PMID- 25398229
TI  - Relapses and disability accumulation in progressive multiple sclerosis.
AB  - OBJECTIVE: We examined the effect of relapses-before and after progression onset
      on the rate of postprogression disability accrual in a progressive multiple
      sclerosis (MS) cohort. METHODS: We studied patients with primary progressive MS
      (n = 322) and bout-onset progressive MS (BOPMS) including single-attack
      progressive MS (n = 112) and secondary progressive MS (n = 421). The effect of
      relapses on time to Expanded Disability Status Scale (EDSS) score of 6 was
      studied using multivariate Cox regression analysis (sex, age at progression, and
      immunomodulation modeled as covariates). Kaplan-Meier analysis was performed
      using EDSS 6 as endpoint. RESULTS: Preprogression relapses (hazard ratio [HR]:
      1.63; 95% confidence interval [CI]: 1.34-1.98), postprogression relapses (HR:
      1.37; 95% CI: 1.11-1.70), female sex (HR: 1.19; 95% CI: 1.00-1.43), and
      progression onset after age 50 years (HR: 1.47; 95% CI: 1.21-1.78) were
      associated with shorter time to EDSS 6. Postprogression relapses occurred in
      29.5% of secondary progressive MS, 10.7% of single-attack progressive MS, and
      3.1% of primary progressive MS. Most occurred within 5 years (91.6%) after
      progressive disease onset and/or before age 55 (95.2%). Immunomodulation after
      onset of progressive disease course (HR: 0.64; 95% CI: 0.52-0.78) seemingly
      lengthened time to EDSS 6 (for BOPMS with ongoing relapses) when analyzed as a
      dichotomous variable, but not as a time-dependent variable. CONCLUSIONS: Pre- and
      postprogression relapses accelerate time to severe disability in progressive MS.
      Continuing immunomodulation for 5 years after the onset of progressive disease or
      until 55 years of age may be reasonable to consider in patients with BOPMS who
      have ongoing relapses.

PMID- 25398231
TI  - Cluster headache and the hypocretin receptor 2 reconsidered: a genetic
      association study and meta-analysis.
AB  - BACKGROUND: Cluster headache is a severe neurological disorder with a complex
      genetic background. A missense single nucleotide polymorphism (rs2653349;
      p.Ile308Val) in the HCRTR2 gene that encodes the hypocretin receptor 2 is the
      only genetic factor that is reported to be associated with cluster headache in
      different studies. However, as there are conflicting results between studies, we
      re-evaluated its role in cluster headache. METHODS: We performed a genetic
      association analysis for rs2653349 in our large Leiden University Cluster
      headache Analysis (LUCA) program study population. Systematic selection of the
      literature yielded three additional studies comprising five study populations,
      which were included in our meta-analysis. Data were extracted according to
      predefined criteria. RESULTS: A total of 575 cluster headache patients from our
      LUCA study and 874 controls were genotyped for HCRTR2 SNP rs2653349 but no
      significant association with cluster headache was found (odds ratio 0.91 (95%
      confidence intervals 0.75-1.10), p = 0.319). In contrast, the meta-analysis that
      included in total 1167 cluster headache cases and 1618 controls from the six
      study populations, which were part of four different studies, showed association
      of the single nucleotide polymorphism with cluster headache (random effect odds
      ratio 0.69 (95% confidence intervals 0.53-0.90), p = 0.006). The association
      became weaker, as the odds ratio increased to 0.80, when the meta-analysis was
      repeated without the initial single South European study with the largest effect
      size. CONCLUSIONS: Although we did not find evidence for association of rs2653349
      in our LUCA study, which is the largest investigated study population thus far,
      our meta-analysis provides genetic evidence for a role of HCRTR2 in cluster
      headache. Regardless, we feel that the association should be interpreted with
      caution as meta-analyses with individual populations that have limited power have
      diminished validity.

PMID- 25398233
TI  - Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.

PMID- 25398234
TI  - Reply: Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.

PMID- 25398235
TI  - Circulating cells contribute to cardiomyocyte regeneration after injury.
AB  - RATIONALE: The contribution of bone marrow-borne hematopoietic cells to the
      ischemic myocardium has been documented. However, a pivotal study reported no
      evidence of myocardial regeneration from hematopoietic-derived cells. The study
      did not take into account the possible effect of early injury-induced signaling
      as the test mice were parabiotically paired to partners immediately after surgery
      induced myocardial injury when cross-circulation has not yet developed.
      OBJECTIVE: To re-evaluate the role of circulating cells in the injured
      myocardium. METHODS AND RESULTS: By combining pulse-chase labeling and parabiosis
      model, we show that circulating cells derived from the parabiont expressed
      cardiac-specific markers in the injured myocardium. Genetic fate mapping also
      revealed that circulating hematopoietic cells acquired cardiac cell fate by means
      of cell fusion and transdifferentiation. CONCLUSIONS: These results suggest that
      circulating cells participate in cardiomyocyte regeneration in a mouse model of
      parabiosis when the circulatory system is fully developed before surgery-induced
      heart injury.

PMID- 25398236
TI  - CD4+ natural killer T cells potently augment aortic root atherosclerosis by
      perforin- and granzyme B-dependent cytotoxicity.
AB  - RATIONALE: CD4(+) natural killer T (NKT) cells augment atherosclerosis in
      apolipoprotein E-deficient (ApoE)(-/-) mice but their mechanisms of action are
      unknown. OBJECTIVES: We investigated the roles of bystander T, B, and NK cells;
      NKT cell-derived interferon-gamma, interleukin (IL)-4, and IL-21 cytokines; and
      NKT cell-derived perforin and granzyme B cytotoxins in promoting CD4(+) NKT cell
      atherogenicity. METHODS AND RESULTS: Transfer of CD4(+) NKT cells into T- and B
      cell-deficient ApoE(-/-)Rag2(-/-) mice augmented aortic root atherosclerosis by
      ~75% that was ~30% of lesions in ApoE(-/-) mice; macrophage accumulation
      similarly increased. Transferred NKT cells were identified in the liver and
      atherosclerotic lesions of recipient mice. Transfer of CD4(+) NKT cells into T-,
      B-cell-deficient, and NK cell-deficient ApoE(-/-)Rag2(-/-)gammaC(-/-) mice also
      augmented atherosclerosis. These data indicate that CD4(+) NKT cells can exert
      proatherogenic effects independent of other lymphocytes. To investigate the role
      of NKT cell-derived interferon-gamma, IL-4, and IL-21 cytokines and perforin and
      granzyme B cytotoxins, CD4(+) NKT cells from mice deficient in these molecules
      were transferred into NKT cell-deficient ApoE(-/-)Jalpha18(-/-) mice. CD4(+) NKT
      cells deficient in IL-4, interferon-gamma, or IL-21 augmented atherosclerosis in
      ApoE(-/-)Jalpha18(-/-) mice by ~95%, ~80%, and ~70%, respectively. Transfer of
      CD4(+) NKT cells deficient in perforin or granzyme B failed to augment
      atherosclerosis. Apoptotic cells, necrotic cores, and proinflammatory VCAM-1
      (vascular cell adhesion molecule) and MCP-1 (monocyte chemotactic protein) were
      reduced in mice receiving perforin-deficient NKT cells. CD4(+) NKT cells are
      twice as potent as CD4(+) T cells in promoting atherosclerosis. CONCLUSIONS:
      CD4(+) NKT cells potently promote atherosclerosis by perforin and granzyme B
      dependent apoptosis that increases postapoptotic necrosis and inflammation.

PMID- 25398237
TI  - Sonoelastography--a useful adjunct for parotid gland ultrasound assessment in
      patients suffering from chronic inflammation.
AB  - BACKGROUND: Shear wave elastography (SWE) is widely used in breast, liver,
      prostate and thyroid evaluations. Elastography provides additional information if
      used to assess parotid gland pathology. We assessed parotid glands by means of
      SWE to compare the parenchyma properties in different types of inflammation.
      MATERIAL/METHODS: Prospective analysis included 78 consecutive patients with
      parotid gland pathology: sialolithiasis (33), Stensen's duct stenosis (15),
      chronic inflammation (10), and primary Sjogren syndrome (pSS) (20) treated at the
      Department of Otolaryngology, Head and Neck Surgery of PUMS. The primary
      predictor variable was type of parotid pathology, and secondary predictor
      variables were patient age and the duration and intensity of complaints.
      Ultrasound pictures were compared with elastography values of parotid parenchyma.
      RESULTS: Mean elasticity values for pSS (111 Kilopascals (kPa), Stensen's duct
      stenosis (63 kPa), sialolithiasis (82 kPa), and chronic inflammation (77 kPa)
      were significantly higher than the mean value for healthy patients (24 kPa).
      Elasticity increased proportionally to the intensity of complaints: mild (51
      kPa), moderate (78 kPa), and strong (90 kPa). Increased elasticity did not
      correspond with ultrasonographic pictures. In pSS the parenchyma was almost twice
      as stiff as in chronic inflammation (p=0.02), although subjective complaints were
      mostly mild or moderate, and the ultrasonographic picture did not present
      features of fibrosis. CONCLUSIONS: Sonoelastography, by improving routine
      ultrasonographic assessment, might be a useful tool for parotid evaluations
      during the course of chronic inflammation. An extraordinarily high degree of
      stiffness was revealed in pSS despite lack of fibrosis by ultrasonography and
      moderate subjective complaints, suggesting that sonoelastography could be a
      valuable diagnostic tool.

PMID- 25398238
TI  - Does henna impact pulse oximetry results?
AB  - OBJECTIVE: To evaluate the effects of henna on the results of pulse oximetry in
      healthy women. METHODS: 100 young women (20-60 years of age) were recruited. The
      Iranian original red henna was used to colour the index finger of THE non
      dominant hand; the middle finger of the same hand was the control. Blood oxygen
      saturation was simultaneously measured by two calibrated pulse oximeters. RESULT:
      Henna did not affect pulse oximetry measurement of oxygen saturation. There was
      no statistically significant difference between the control and the henna dyed
      fingers. CONCLUSIONS: Henna is not likely to change the accuracy of oxygen
      saturation measured by pulse oximeter. CLINICAL TRIAL REGISTRATION:
      20120906159N20.

PMID- 25398239
TI  - Spectrum of patients intentionally poisoned with an emulsified concentrate
      pendimethalin herbicide.
AB  - OBJECTIVE: Studies on the acute toxicity of pendimethalin herbicide in humans are
      limited. Therefore, this study investigated the clinical characteristics of acute
      intentional pendimethalin herbicide poisoning. MATERIAL AND METHOD: A
      retrospective observational case series was conducted involving 17 patients with
      a history of intentional pendimethalin herbicide ingestion. Data were collected
      on clinical manifestations, management and final outcome. RESULT: The mortality
      rate was 0%; however, four patients (23.5%) exhibited metabolic acidosis,
      hypotension or respiratory failure within the first 24 h after ingestion and
      required admission to the intensive care unit. The most common complication was
      respiratory failure, followed by hypotension. Complicated patients tended to show
      an altered mental state and X-ray abnormalities at presentation. DISCUSSION AND
      CONCLUSIONS: Physicians should be aware that patients who have been poisoned with
      pendimethalin herbicide, and particularly patients with a depressed mental state
      and X-ray abnormalities at presentation, may exhibit metabolic acidosis,
      hypotension, respiratory failure or pancreatitis.

PMID- 25398240
TI  - Kinin receptor agonism restores hindlimb postischemic neovascularization capacity
      in diabetic mice.
AB  - Limb ischemia is a major complication of thromboembolic diseases. Diabetes
      worsens prognosis by impairing neovascularization. Genetic or pharmacological
      inactivation of the kallikrein-kinin system aggravates limb ischemia in
      nondiabetic animals, whereas angiotensin I-converting enzyme/kininase II
      inhibition improves outcome. The role of kinins in limb ischemia in the setting
      of diabetes is not documented. We assessed whether selective activation of kinin
      receptors by pharmacological agonists can influence neovascularization in
      diabetic mice with limb ischemia and have a therapeutic effect. Selective
      pseudopeptide kinin B1 or B2 receptor agonists resistant to peptidase action were
      administered by osmotic minipumps at a nonhypotensive dosage for 14 days after
      unilateral femoral artery ligation in mice previously rendered diabetic by
      streptozotocin. Comparison was made with ligatured, nonagonist-treated
      nondiabetic and diabetic mice. Diabetes reduced neovascularization, assessed by
      microangiography and histologic capillary density analysis, by roughly 40%. B1
      receptor agonist or B2 receptor agonist similarly restored neovascularization in
      diabetic mice. Neovascularization in agonist-treated diabetic mice was
      indistinguishable from nondiabetic mice. Both treatments restored blood flow in
      the ischemic hindfoot, measured by laser-Doppler perfusion imaging. Macrophage
      infiltration increased 3-fold in the ischemic gastrocnemius muscle during B1
      receptor agonist or B2 receptor agonist treatment, and vascular endothelial
      growth factor (VEGF) level increased 2-fold. Both treatments increased, by 50
      100%, circulating CD45/CD11b-positive monocytes and CD34(+)/VEGFR2(+) progenitor
      cells. Thus, selective pharmacological activation of B1 or B2 kinin receptor
      overcomes the effect of diabetes on postischemic neovascularization and restores
      tissue perfusion through monocyte/macrophage mobilization. Kinin receptors are
      potential therapeutic targets in limb ischemia in diabetes. 

PMID- 25398242
TI  - Polythiol-containing, recombinant mannosylated-albumin is a superior CD68+/CD206+
      Kupffer cell-targeted nanoantioxidant for treatment of two acute hepatitis
      models.
AB  - Since reactive oxygen species (ROS) derived from Kupffer cells (KC), especially
      CD68(+) KC, play a key role in the induction of hepatic oxidative stress and
      injuries, we developed a polythiolated- and mannosylated human serum albumin (SH
      Man-HSA), which functions as a novel nanoantioxidant for delivering thiol to
      CD68(+) KC. In vitro electron paramagnetic resonance coupled with
      pharmacokinetics and immunohistochemical studies showed that SH-Man-HSA possessed
      powerful radical-scavenging activity and rapidly and selectively delivered thiols
      to the liver via mannose receptor (CD206) on CD68(+) cells. SH-Man-HSA
      significantly improved the survival rate of concanavalin-A (Con-A)-treated mice.
      Moreover, SH-Man-HSA exhibited excellent hepatoprotective functions, not by
      decreasing tumor necrosis factor or interferon-gamma production that is closely
      associated with Con-A-induced hepatitis, but by suppressing ROS production.
      Interestingly, the protective effect of SH-Man-HSA was superior to N-acetyl
      cysteine (NAC). This could be attributed to the difference in the inhibition of
      hepatic oxidative stress between the two antioxidants depending on their
      potential for thiol delivery to the liver. Similar results were also observed for
      acetaminophen (APAP)-induced hepatopathy models. Flow cytometric data further
      confirmed that an increase in F4/80(+)/ROS(+) cells was dramatically decreased by
      SH-Man-HSA. The administration of SH-Man-HSA at 4 hours following a Con-A or APAP
      injection also exhibited a profound hepatoprotective action against these
      hepatitis models, whereas this was not observed for NAC. It can be concluded
      therefore that SH-Man-HSA has great potential for use in a rescue therapy for
      hepatopathy as a nanoantioxidant because of its ability to efficiently and
      rapidly deliver thiols to CD68(+)/CD206(+) KC. 

PMID- 25398243
TI  - Medical reasons behind player departures from male and female professional tennis
      competitions.
AB  - BACKGROUND: The number of retirements, withdrawals, and "lucky losers" (the
      replacement of a player who withdraws before the start of the tournament by a
      losing player from the qualifying round) from professional tennis tournaments has
      increased, but the reasons behind such departures have not yet been analyzed. An
      official consensus statement has been conducted to allow a general categorization
      of injuries in tennis. PURPOSE: To determine the reasons for departure and injury
      rates in professional tennis. STUDY DESIGN: Descriptive epidemiology study.
      METHODS: All reasons for departures were collected from official Association of
      Tennis Professionals (ATP) and Women's Tennis Association (WTA) web pages. All
      tournaments apart from the 4 major competitions (the Australian Open, French
      Open, Wimbledon, and US Open) were included for the period 2001-2012 for men and
      women. Personal data, tournament information, surface, match setting, date, and
      reason were obtained for each departure scenario. RESULTS: Variations in
      departure and injury rates were seen throughout the season. Women left and were
      injured significantly more than men. Women mainly left because of thigh injuries,
      whereas men left mainly because of back injuries. Playing surface only had an
      influence on the risk of lower back injuries. Only women's departures were
      affected by the tournament round. CONCLUSION: A high number of departures from
      tournaments have occurred during the past 10 years on the ATP and WTA circuits.
      Injuries were the main reasons of these departures, regardless of the type of
      departure and player sex. The back and thigh were the main locations of injuries
      for men and women, respectively.

PMID- 25398244
TI  - The effect of previous hamstring strain injuries on the change in eccentric
      hamstring strength during preseason training in elite Australian footballers.
AB  - BACKGROUND: Hamstring strain injuries (HSIs) are the most common injury type in
      Australian football, and the rate of recurrence has been consistently high for a
      number of years. Long-lasting neuromuscular inhibition has been noted in
      previously injured athletes, but it is not known if this influences the athlete's
      adaptive response to training. PURPOSE: To determine if elite Australian
      footballers with a prior unilateral HSI (previously injured group) display less
      improvement in eccentric hamstring strength during preseason training compared
      with athletes without a history of HSIs (control group). STUDY DESIGN: Cohort
      study; Level of evidence, 2. METHODS: A total of 99 elite Australian footballers
      (17 with a history of unilateral HSIs in the previous 12-month period)
      participated in this study. Eccentric hamstring strength was assessed at the
      start and end of preseason training using an instrumented Nordic hamstring
      device. The change in eccentric strength across the preseason was determined in
      absolute terms and normalized to the start of preseason strength. The start of
      preseason strength was used as a covariate to control for differences in starting
      strength. RESULTS: The left and right limbs in the control group showed no
      difference in absolute or relative change (left limb: 60.7 +/- 72.9 N and 1.28 +/
      0.34 N, respectively; right limb: 48.6 +/- 83.8 N and 1.24 +/- 0.43 N,
      respectively). Similarly, the injured and uninjured limbs in the previously
      injured group showed no difference in either absolute or relative change (injured
      limb: 13.1 +/- 57.7 N and 1.07 +/- 0.18 N, respectively; uninjured limb: 14.7 +/-
      54.0 N and 1.07 +/- 0.22 N, respectively). The previously injured group displayed
      significantly less increase in eccentric hamstring strength across the preseason
      (absolute change, 13.9 +/- 55.0 N; relative change, 1.07 +/- 0.20 N) compared
      with the control group (absolute change, 54.6 +/- 78.5 N; relative change, 1.26
      +/- 0.39 N) for both absolute and relative measures (P < .001), even after
      controlling for differences in the start of preseason eccentric hamstring
      strength, which had a significant effect on strength improvement. CONCLUSION:
      Elite Australian footballers with a unilateral history of HSIs displayed less
      improvement in eccentric hamstring strength across preseason training. The
      smaller improvements were not restricted to the previously injured limb as the
      contralateral limb also displayed similarly small improvements in eccentric
      strength. Whether this is the cause of or the result of an injury remains to be
      seen, but it has the potential to contribute to the risk of hamstring strain
      reinjuries.

PMID- 25398245
TI  - Lumbopelvic kinematic characteristics of golfers with limited hip rotation.
AB  - BACKGROUND: While the biomechanical characteristics of the golf swing are well
      established, the lumbopelvic kinematic characteristics of professional golfers
      with limited hip internal rotation warrant further investigation. PURPOSE: The
      specific aim was to ascertain mechanical differences in lumbopelvic-hip movement
      of asymptomatic professional golfers with and without limited hip internal
      rotation during the golf swing. STUDY DESIGN: Controlled laboratory study.
      METHODS: Thirty professional male golfers (aged 25-35 years and 0 handicap
      matched) were classified into either the limited hip internal motion (LHIM) group
      (range of motion<20 degrees ) or the normal hip internal motion (NHIM) group
      (range of motion>=30 degrees ). All participants underwent clinical tests (muscle
      strength, muscle length, and range of motion) and a biomechanical assessment
      using 8 infrared optic cameras in a motion analysis system. Independent t tests
      were performed to determine potential mean differences in muscle strength,
      length, and range of motion and lumbopelvic kinematics at P<.05. RESULTS:
      Kinematic analysis revealed that the LHIM group showed significantly greater
      lumbar flexion (P<.001), right and left axial rotation (P<.025), and right-side
      lateral bending (P=.003) than the NHIM group. A greater pelvic posterior tilt was
      observed in the LHIM group when compared with the NHIM group (P=.021). Clinical
      tests showed reduced internal rotator muscle strength and shorter muscle length
      in the iliopsoas (P=.017) and hamstring (P<.001) among those in the LHIM group
      when compared with the NHIM group. CLINICAL RELEVANCE: The study data suggest
      that constraints to hip joint internal rotation, along with muscle strength
      imbalances between the agonist and antagonist muscles and muscle tightness, are
      associated with substantially greater lumbopelvic movement during the golf swing.

PMID- 25398241
TI  - Delta9-tetrahydrocannabinol and endocannabinoid degradative enzyme inhibitors
      attenuate intracranial self-stimulation in mice.
AB  - A growing body of evidence implicates endogenous cannabinoids as modulators of
      the mesolimbic dopamine system and motivated behavior. Paradoxically, the
      reinforcing effects of Delta(9)-tetrahydrocannabinol (THC), the primary
      psychoactive constituent of cannabis, have been difficult to detect in
      preclinical rodent models. In this study, we investigated the impact of THC and
      inhibitors of the endocannabinoid hydrolytic enzymes fatty acid amide hydrolase
      (FAAH) and monoacylglycerol lipase (MAGL) on operant responding for electrical
      stimulation of the medial forebrain bundle [intracranial self-stimulation
      (ICSS)], which is known to activate the mesolimbic dopamine system. These drugs
      were also tested in assays of operant responding for food reinforcement and
      spontaneous locomotor activity. THC and the MAGL inhibitor JZL184 (4-[bis(1,3
      benzodioxol-5-yl)hydroxymethyl]-1-piperidinecarboxylic acid 4-nitrophenyl ester)
      attenuated operant responding for ICSS and food, and also reduced spontaneous
      locomotor activity. In contrast, the FAAH inhibitor PF-3845 (N-3-pyridinyl-4-[[3
      [[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide) was
      largely without effect in these assays. Consistent with previous studies showing
      that combined inhibition of FAAH and MAGL produces a substantially greater
      cannabimimetic profile than single enzyme inhibition, the dual FAAH-MAGL
      inhibitor SA-57 (4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2
      (methylamino)-2-oxoethyl ester) produced a similar magnitude of ICSS depression
      as that produced by THC. ICSS attenuation by JZL184 was associated with increased
      brain levels of 2-arachidonoylglycerol (2-AG), whereas peak effects of SA-57 were
      associated with increased levels of both N-arachidonoylethanolamine (anandamide)
      and 2-AG. The cannabinoid receptor type 1 receptor antagonist rimonabant, but not
      the cannabinoid receptor type 2 receptor antagonist SR144528, blocked the
      attenuating effects of THC, JZL184, and SA-57 on ICSS. Thus, THC, MAGL
      inhibition, and dual FAAH-MAGL inhibition not only reduce ICSS, but also decrease
      other reinforced and nonreinforced behaviors. 

PMID- 25398246
TI  - A novel approach for establishing cardiovascular drug efficacy.

PMID- 25398247
TI  - Protective effects of biochanin A on articular cartilage: in vitro and in vivo
      studies.
AB  - BACKGROUND: Increased production of matrix metalloproteinases (MMPs) is closely
      related to the progression of osteoarthritis (OA). The present study was
      performed to investigate the potential value of biochanin A in inhibition of MMP
      expression in both rabbit chondrocytes and an animal model of OA. METHODS: MTT
      assay was performed to assess chondrocyte survival in monolayers. The mRNA and
      protein expression of MMPs (including MMP-1, MMP-3, and MMP-13) and tissue
      inhibitor of metalloproteinase-1 (TIMP-1) in interleukin-1 < beta > (IL-1beta)
      induced rabbit chondrocytes were determined by quantitative real-time PCR and
      enzyme-linked immunosorbent assay (ELISA), respectively. The involvement of the
      NF-kappaB (NF-kappaB) pathway activated by IL-1beta was determined by western
      blotting. The in vivo effects of biochanin A were evaluated by intra-articular
      injection in an experimental OA rabbit model induced by anterior cruciate
      ligament transection (ACLT). RESULTS: Biochanin A downregulated the expression of
      MMPs and upregulated TIMP-1 at both the mRNA and protein levels in IL-1beta
      induced chondrocytes in a dose-dependent manner. In addition, IL-1beta-induced
      activation of NF-kappaB was attenuated by biochanin A, as determined by western
      blotting. Moreover, biochanin A decreased cartilage degradation as determined by
      both morphological and histological analyses in vivo. CONCLUSIONS: Taken
      together, these findings suggest that biochanin A may be a useful agent in the
      treatment and prevention of OA.

PMID- 25398248
TI  - Proteomics informed by transcriptomics reveals  Hendra virus sensitizes bat cells
      to TRAIL-mediated  apoptosis.
AB  - BACKGROUND: Bats are a major reservoir of emerging infectious viruses. Many of
      these viruses are highly pathogenic to humans however bats remain asymptomatic.
      The mechanism by which bats control viral replication is unknown. Here we utilize
      an integrated approach of proteomics informed by transcriptomics to compare the
      response of immortalized bat and human cells following infection with the highly
      pathogenic bat-borne Hendra virus (HeV). RESULTS: The host response between the
      cell lines was significantly different at both the mRNA and protein levels. Human
      cells demonstrated minimal response eight hours post infection, followed by a
      global suppression of mRNA and protein abundance. Bat cells demonstrated a robust
      immune response eight hours post infection, which led to the up-regulation of
      apoptosis pathways, mediated through the tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). HeV sensitized bat cells to TRAIL-mediated apoptosis, by
      up-regulating death receptor transcripts. At 48 and 72 hours post infection, bat
      cells demonstrated a significant increase in apoptotic cell death. CONCLUSIONS:
      This is the first study to comprehensively compare the response of bat and human
      cells to a highly pathogenic zoonotic virus. An early induction of innate immune
      processes followed by apoptosis of virally infected bat cells highlights the
      possible involvement of programmed cell death in the host response. Our study
      shows for the first time a side-by-side high-throughput analysis of a dangerous
      zoonotic virus in cell lines derived from humans and the natural bat host. This
      enables a way to search for divergent mechanisms at a molecular level that may
      influence host pathogenesis.

PMID- 25398249
TI  - Comparison of inflammatory markers in induced and spontaneous sputum in a cohort
      of COPD patients.
AB  - BACKGROUND: Sputum induction is a non-invasive method for obtaining measurements
      of inflammation in the airways. Whether spontaneously sampled sputum can be a
      valid surrogate is unknown. The aim of this study was to compare levels of six
      inflammatory markers in sputum pairs consisting of induced and spontaneous sputum
      sampled on the same consultation either in a stable state or during exacerbations
      of chronic obstructive pulmonary disease (COPD). METHODS: 433 COPD patients aged
      40-76, Global initiative for chronic Obstructive Lung Disease (GOLD) stage II-IV
      were enrolled in 2006/07 and followed every six months for three years. 356
      patients were followed for potential exacerbations. Interleukin-6, interleukin-8,
      interleukin-18, interferon gamma-inducible protein-10, monokine induced by gamma
      interferon and tumor necrosis factor-alpha (IL-6, IL-8, IL-18, IP-10, MIG and TNF
      alpha) were measured by bead based multiplex immunoassay in 60 paired sputum
      samples from 45 patients. Albumin was measured by enzyme immunoassay, for
      concentration correction. Culturing for bacterial growth was performed on 24
      samples. Bland-Altman plots were used to assess agreement. The paired non
      parametric Wilcoxon signed-rank test, the non-parametric Spearman's rank
      correlation test and Kruskal-Wallis test were used for statistical analyses. For
      all analyses, a p-value < 0.05 was considered significant. RESULTS: Agreement
      between the two measurements was generally low for all six markers. TNF-alpha was
      significantly higher in spontaneous sputum at exacerbations (p = 0.002) and
      trending higher at the steady state (p = 0.06). Correlation coefficients between
      the levels of markers in induced and spontaneous sputum varied between 0.58 (IL
      18) to 0.83 (IP-10). In spontaneous sputum IL-18 and MIG were higher in ex
      smokers (p < 0.05). The levels of all markers were higher in GOLD stage III & IV
      except for IL-6 in spontaneous sputum and IL-18 in induced sputum, compared with
      GOLD stage II, although not statistically significant. In spontaneous sputum the
      levels of IL-6 were significantly higher if Haemophilus influenzae (HI) was not
      cultured. CONCLUSION: We observed a low agreement and significant differences in
      inflammatory markers between induced and spontaneous sputum, both at steady state
      and exacerbations. We recommend considering sampling method when reporting on
      inflammatory markers in sputum.

PMID- 25398250
TI  - Interaction of the anticancer gallium(III) complexes of 8-hydroxyquinoline and
      maltol with human serum proteins.
AB  - Tris(8-quinolinolato)gallium(III) (KP46) and tris(maltolato)gallium(III) (GaM)
      are promising orally active antitumor metallodrugs currently undergoing clinical
      trials. Their interaction with human serum albumin (HSA) and transferrin (Tf) was
      studied in detail in aqueous solution by the combination of various methods such
      as spectrofluorometry, UV-vis spectrophotometry, (1)H and saturation transfer
      difference NMR spectroscopy, and ultrafiltration-UV-vis spectrophotometry.
      Binding data were evaluated quantitatively. Tf was found to replace the original
      ligand much less efficiently in KP46 than in GaM, whereas a significant
      noncovalent binding of KP46 with HSA (log K' = 4.04) retaining the coordination
      environment around gallium(III) was found. The interaction between HSA and KP46
      was also confirmed by protein-complex modeling calculations. On the basis of the
      conditional stability constants, the distribution of gallium(III) in serum was
      computed and compared for these metallodrugs under physiological conditions, and
      revealed the prominent role of HSA in the case of KP46 and that of Tf for GaM. 

PMID- 25398252
TI  - Subcellular localization of MTA proteins in normal and cancer cells.
AB  - The subcellular localization of a protein is closely linked to and indicates its
      function. The metastatic tumor antigen (MTA) family has been under continuous
      investigation since its identification two decades ago. MTA1, MTA2, and MTA3 are
      the main members of the MTA family. MTA1, as the representative member of this
      family, has been shown to be widely expressed in both embryonic and adult
      tissues, as well as in normal and cancerous conditions, indicating that MTA1 has
      functions both in physiological and pathological contexts. MTA1 is expressed at a
      higher level in most cancers than in their normal tissue counterparts. Even in
      normal cells, MTA1 levels vary a great deal from tissue to tissue. Importantly,
      MTA1 shows a multiple localization pattern in the cell, as do MTA2 and MTA3.
      Different MTA components in different subcellular compartments may exert
      different molecular functions in the cell. Previous studies revealed that MTA1
      and MTA2 are predominately localized to the nucleus, while MTA3 is observed in
      both the nucleus and cytoplasm. Recent studies have reported that MTA1 is located
      in the nucleus, cytoplasm, and the nuclear envelope. In the nucleus, MTA1
      dynamically interacts with chromatin in a MTA1-K532 methylation-dependent manner,
      whereas cytoplasmic MTA1 binds to the microtubule skeleton. MTA1 also shows a
      dynamic distribution during the cell cycle. Further investigations are needed to
      identify the exact subcellular localizations of MTA proteins. We review the sub
      cellular localization patterns of the MTA family members and give a comprehensive
      overview of their respective molecular activities in multiple contexts.

PMID- 25398253
TI  - An RNA-seq transcriptome analysis of floral buds of an interspecific Brassica
      hybrid between B. carinata and B. napus.
AB  - Interspecific hybridizations promote gene transfer between species and play an
      important role in plant speciation and crop improvement. However, hybrid
      sterility that commonly found in the first generation of hybrids hinders the
      utilization of interspecific hybridization. The combination of divergent parental
      genomes can create extensive transcriptome variations, and to determine these
      gene expression alterations and their effects on hybrids, an interspecific
      Brassica hybrid of B. carinata * B. napus was generated. Scanning electron
      microscopy analysis indicated that some of the hybrid pollen grains were
      irregular in shape and exhibited abnormal exine patterns compared with those from
      the parents. Using the Illumina HiSeq 2000 platform, 39,598, 32,403 and 42,208
      genes were identified in flower buds of B. carinata cv. W29, B. napus cv.
      Zhongshuang 11 and their hybrids, respectively. The differentially expressed
      genes were significantly enriched in pollen wall assembly, pollen exine
      formation, pollen development, pollen tube growth, pollination, gene
      transcription, macromolecule methylation and translation, which might be
      associated with impaired fertility in the F1 hybrid. These results will shed
      light on the mechanisms underlying the low fertility of the interspecific hybrids
      and expand our knowledge of interspecific hybridization.

PMID- 25398254
TI  - Sex differences in new-onset heart failure.
AB  - BACKGROUND: Sex differences in patients with established heart failure have been
      well described, but much less is known in the development of heart failure.
      METHODS: We studied sex-specific incidence and risk of new-onset heart failure in
      8592 subjects (mean age 49.2 +/- 12.7 years; 50.1 % women) of the Prevention of
      REnal and Vascular ENdstage Disease (PREVEND) study and distinguished reduced and
      preserved ejection fraction (HFrEF <40 % and HFpEF >50 %). RESULTS: Of 374 cases
      with incident heart failure, 241 (64.4 %) occurred in men and 133 (35.6 %) in
      women (median follow-up 12.5 years; 96,550 person-years). Men developed heart
      failure earlier (7.0 vs. 8.6 years; P < 0.001). Incidence rates per 1,000 person
      years in women compared to men were lower for HFrEF (1.2 vs. 3.0 %; P < 0.001),
      but higher for HFpEF (1.2 vs. 0.7 %; P < 0.001). Women developed HFpEF later in
      life than HFrEF (75.1 vs. 69.7 years; P = 0.033), while men showed no significant
      difference (72.2 vs. 69.5 years; P = 0.116). Multivariable competing risks
      analyses showed that women had lower risk for HFrEF (subhazard ratio = 0.47; 95 %
      CI 0.29-0.76, P = 0.002) but higher risk for HFpEF (subhazard ratio = 2.16; 95 %
      CI 1.21-3.83, P = 0.009) than men. Among all risk factors, only atrial
      fibrillation had a sex-specific predictive value and increased risk specifically
      for women (P-for interaction = 0.016). CONCLUSIONS: In a middle-aged population,
      men developed heart failure more frequently and at a younger age than women.
      However, women had higher risk for HFpEF, with atrial fibrillation being a
      specific female risk factor.

PMID- 25398256
TI  - The A395T mutation in ERG11 gene confers fluconazole resistance in Candida
      tropicalis causing candidemia.
AB  - The mechanism of fluconazole resistance in Candida tropicalis is still unclear.
      Recently, we isolated a fluconazole-resistant strain of C. tropicalis from the
      blood specimen of a patient with candidemia in China. In vitro antifungal
      susceptibility of the isolate was determined by using CLSI M27-A3 and E-test
      methods. The sequence of ERG11 gene was then analyzed, and the three-dimensional
      model of Erg11p encoded by ERG11 gene was also investigated. The sequencing of
      ERG11 gene revealed the mutation of A395T in this fluconazole-resistant isolate
      of C. tropicalis, resulting in the Y132F substitution in Erg11p. Sequence
      alignment and three-dimensional model comparison of Erg11ps showed high
      similarity between fluconazole-susceptible isolates of C. tropicalis and Candida
      albicans. The comparison of the three-dimensional models of Erg11ps demonstrated
      that the position of the Y132F substitution in this isolate of C. tropicalis is
      identical to the isolate of C. albicans with fluconazole resistance resulting
      from Y132F substitution in Erg11p. Hence, we ascertain that the Y132F
      substitution of Erg11p caused by A395T mutation in ERG11 gene confers the
      fluconazole resistance in C. tropicalis. 

PMID- 25398255
TI  - Clinical interpretation of genetic variants in arrhythmogenic right ventricular
      cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiac entity
      characterized by right ventricular, or biventricular, fibrofatty replacement of
      myocardium. Structural alterations may lead to sudden cardiac death, mainly in
      young males during exercise. Autosomal dominant pattern of inheritance is
      reported in most parts of pathogenic genetic variations identified. Currently, 13
      genes have been associated with the disease but nearly 40 % of clinically
      diagnosed cases remain without a genetic diagnosis. New genetic technologies
      allow further genetic analysis, generating a significant amount of genetic data
      in novel genes, which is often classified as of ambiguous significance. We focus
      on genetic advances of arrhythmogenic right ventricular cardiomyopathy, helping
      clinicians to interpret and translate genetic data into clinical practice. 

PMID- 25398257
TI  - A Comparison of Methamphetamine Users to a Matched NHANES Cohort: Propensity
      Score Analyses for Oral Health Care and Dental Service Need.
AB  - Dental problems are among the most frequently reported health issues of drug
      users. This study describes, among the largest population of methamphetamine (MA)
      users to date (N = 459, including both HIV-negative and HIV-positive
      participants) oral hygiene practice, dental care access, and dental quality of
      life. A matched control group from the Third National Health and Nutrition
      Examination Survey was utilized. Findings conclusively establish that MA users
      have severe oral health deficits compared to the general population: they are 3.5
      times more likely to experience painful toothaches, 6.6 times to experience
      difficulty eating, and 8.6 times to be self-conscious due to dental appearance.
      HIV-positive users were more likely to have regular dental visits than HIV
      negative users. Severity of use (both high-frequency use as well as injection as
      the method) was associated with poorer oral health care. Despite the magnitude of
      the need, few MA users receive the needed care.

PMID- 25398258
TI  - Health Services for Behavioral Problems in Pediatric Primary Care.
AB  - The aim of this research was to explore primary care pediatricians' experiences
      in delivering behavioral health services in their own practices within the
      Nebraska context. An online survey was sent to the 154 primary care pediatricians
      who are members of the Nebraska chapter of the American Academy of Pediatrics.
      Questions explored their management of behavioral problems, attitudes, and
      perceived barriers to providing behavioral health services in their practices.
      Seventy pediatricians completed the survey (47%). The majority of pediatricians
      reported seeing substantial numbers of children with behavioral problems. Eighty
      five percent believed that most emotional and behavioral complaints could be
      managed by the pediatrician. Eighty-eight percent believed that the parents would
      prefer to receive services for their children's behavioral problems in the
      primary care office. Most felt that their training in mental health issues was
      inadequate. Pediatricians in this survey feel that pediatric behavioral problems
      are best managed in the primary care office and perceive that parents also prefer
      this setting. Improving training in behavioral health in pediatrics is necessary
      to meet the delivery of much needed behavioral health care to children and
      families.

PMID- 25398259
TI  - Oxygen supply to the fetal cerebral circulation in hypoplastic left heart
      syndrome: a simulation study based on the theoretical models of fetal
      circulation.
AB  - Hypoxia due to congenital heart diseases (CHDs) adversely affects brain
      development during the fetal period. Head circumference at birth is closely
      associated with neuropsychiatric development, and it is considerably smaller in
      newborns with hypoplastic left heart syndrome (HLHS) than in normal newborns. We
      performed simulation studies on newborns with CHD to evaluate the cerebral
      circulation during the fetal period. The oxygen saturation of cerebral blood flow
      in newborns with CHD was simulated according to a model for normal fetal
      circulation in late pregnancy. We compared the oxygen saturation of cerebral
      blood flow between newborns with tricuspid atresia (TA; a disease showing
      univentricular circulation and hypoplasia of the right ventricle), those with
      transposition of the great arteries (TGA; a disease showing abnormal mixing of
      arterial and venous blood), and those with HLHS. The oxygen saturation of
      cerebral blood flow in newborns with normal circulation was 75.7 %, whereas it
      was low (49.5 %) in both newborns with HLHS and those with TA. Although the
      oxygen level is affected by the blood flow through the foramen ovale, the oxygen
      saturation in newborns with TGA was even lower (43.2 %). These data, together
      with previous reports, suggest that the cerebral blood flow rate is decreased in
      newborns with HLHS, and the main cause was strongly suspected to be retrograde
      cerebral perfusion through a patent ductus arteriosus. This study provides
      important information about the neurodevelopmental prognosis of newborns with
      HLHS and suggests the need to identify strategies to resolve this unfavorable
      cerebral circulatory state in utero. 

PMID- 25398260
TI  - The fontan procedure: now what?

PMID- 25398261
TI  - Autonomic dysfunction associated with Type 1 diabetes: a role for fitness?

PMID- 25398262
TI  - Membrane inlet mass spectrometry for homeland security and forensic applications.
AB  - A man-portable membrane inlet mass spectrometer has been built and tested to
      detect and monitor characteristic odors emitted from the human body and also from
      threat substances. In each case, a heated membrane sampling probe was used.
      During human scent monitoring experiments, data were obtained for inorganic gases
      and volatile organic compounds emitted from human breath and sweat in a confined
      space. Volatile emissions were detected from the human body at low ppb
      concentrations. Experiments with compounds associated with narcotics, explosives,
      and chemical warfare agents were conducted for a range of membrane types. Test
      compounds included methyl benzoate (odor signature of cocaine), piperidine
      (precursor in clandestine phencyclidine manufacturing processes), 2-nitrotoluene
      (breakdown product of TNT), cyclohexanone (volatile signature of plastic
      explosives), dimethyl methylphosphonate (used in sarin and soman nerve agent
      production), and 2-chloroethyl ethyl sulfide (simulant compound for sulfur
      mustard gas). Gas phase calibration experiments were performed allowing sub-ppb
      LOD to be established. The results showed excellent linearity versus
      concentration and rapid membrane response times. 

PMID- 25398264
TI  - Contextual barriers to discussing a schizophrenia diagnosis with patients and
      families: need for leadership and teamwork training in psychiatry.
AB  - OBJECTIVE: This research sought to gain insight into the processes used by
      clinicians to discuss a schizophrenia diagnosis with patients/families, with the
      aim of informing the development of a communications skills training program.
      METHODS: A generic qualitative methodological approach was used. Sixteen mental
      health clinicians were recruited. Semi-structured individual interviews were used
      to explore their perceptions and experiences communicating a schizophrenia
      diagnosis. Interviews were recorded, transcribed, and thematic analysis
      undertaken. RESULTS: There were five key themes relating to the process of
      communication about a diagnosis of schizophrenia: (1) orientation to patient
      care, (2) planning of communication, (3) the impact of team leadership and
      inter/intra-professional functioning on communication tasks, (4) the roles of
      different clinicians in communicating about diagnosis and treatment, and (5) time
      and resource deficiencies. Despite expressing care and concern for vulnerable
      patients and embracing the concept of multidisciplinary teams, communicating
      diagnostic information to patients and families was generally unplanned for, with
      little consistency regarding leadership approaches, or how the team communicated
      diagnostic information to the patient and family. This contributed to tensions
      between different team members. CONCLUSION: The findings demonstrated a number of
      issues compromising good communication around a schizophrenia diagnosis, both in
      terms of clinician skill and clinical context, and support the importance of
      education and training for all members of the multidisciplinary team about their
      role in the communication process.

PMID- 25398265
TI  - Qualitative Literature Review of the Prevalence of Depression in Medical Students
      Compared to Students in Non-medical Degrees.
AB  - PURPOSE: The purpose of this study is to review studies published in English
      between 1 January 2000 and 16 June 2014, in peer-reviewed journals, that have
      assessed the prevalence of depression, comparing medical students and non-medical
      students with a single evaluation method. METHOD: The databases PubMed, Medline,
      EMBASE, PsycINFO, and Scopus were searched for eligible articles. Searches used
      combinations of the Medical Subject Headings medical student and depression.
      Titles and abstracts were reviewed to determine eligibility before full-text
      articles were retrieved, which were then also reviewed. RESULTS: Twelve studies
      met eligibility criteria. Non-medical groups surveyed included dentistry,
      business, humanities, nursing, pharmacy, and architecture students. One study
      found statistically significant results suggesting that medical students had a
      higher prevalence of depression than groups of non-medical students; five studies
      found statistically significant results indicating that the prevalence of
      depression in medical students was less than that in groups of non-medical
      students; four studies found no statistically significant difference, and two
      studies did not report on the statistical significance of their findings. One
      study was longitudinal, and 11 studies were cross-sectional. CONCLUSION: While
      there are limitations to these comparisons, in the main, the reviewed literature
      suggests that medical students have similar or lower rates of depression compared
      to certain groups of non-medical students. A lack of longitudinal studies meant
      that potential common underlying causes could not be discerned, highlighting the
      need for further research in this area. The high rates of depression among
      medical students indicate the continuing need for interventions to reduce
      depression.

PMID- 25398263
TI  - An explorative study of metabolic responses to mental stress and yoga practices
      in yoga practitioners, non-yoga practitioners and individuals with metabolic
      syndrome.
AB  - BACKGROUND: Stress places a metabolic burden on homeostasis and is linked to
      heightened sympathetic activity, increased energy expenditure and pathology. The
      yogic state is a hypometabolic state that corresponds with mind-body coherence
      and reduced stress. This study aimed to investigate metabolic responses to stress
      and different yoga practices in regular yoga practitioners (YP), non-yoga
      practitioners (NY) and metabolic syndrome patients (MS). METHODS: YP (n = 16), NY
      (n = 15) and MS (n = 15) subjects underwent an experimental protocol that
      comprised of different 5-minute interventions including mental arithmetic stress
      test (MAST), alternate nostril breathing (ANB), Kapabhati breathing (KB) and
      meditation (Med) interspersed with 5 minutes of quiet resting (neutral condition
      (NC)). During the intervention periods continuous body weight adjusted oxygen
      consumption (VO2ml/min/kg) was measured using open circuit indirect calorimetry
      with a canopy hood. RESULTS: This is the first study to report oxygen consumption
      (OC) in yoga practitioners during and after MAST and the first to report both
      within and between different populations. The results were analysed with SPSS 16
      using 3X9 mixed factorial ANOVAs. The single between-subject factor was group
      (YP, NY and MS), the single within-subject factor was made up of the nine
      intervention phases (NC1, MAST, NC2, ANB, NC3, KB, NC4, Med, NC5). The results
      demonstrated that the regular YP group had significantly less OC and greater
      variability in their OC across all phases compared to the MS group (p = .003) and
      NY group (p = .01). All groups significantly raised their OC during the mental
      arithmetic stress, however the MS group had a significantly blunted post-stress
      recovery whereas the YP group rapidly recovered back to baseline levels with post
      stress recovery being greater than either the NY group or MS group. CONCLUSIONS:
      Yoga practitioners have greater metabolic variability compared to non-yoga
      practitioners and metabolic syndrome patients with reduced oxygen requirements
      during resting conditions and more rapid post-stress recovery. OC in metabolic
      syndrome patients displays significantly blunted post-stress recovery
      demonstrating reduced metabolic resilience. Our results support the findings of
      previous randomised trials that suggest regular yoga practice may mitigate
      against the effects of metabolic syndrome. CLINICAL TRIAL NUMBER:
      ACTRN12614001075673; Date of Registration: 07/10/2014.

PMID- 25398266
TI  - A comparison of longitudinal and block rotations for a psychiatric resident
      consultation-liaison experience.
AB  - OBJECTIVE: Consultation-liaison psychiatry (CLPsych) is a required experience for
      psychiatry residents. There is considerable variation in the structure of the
      experience. We sought to compare a longitudinal and block design for a CLPsych
      residency experience. METHODS: This research was conducted in the context of a
      naturalist transition from a longitudinal CLPsych rotation design to a block
      rotation design. We surveyed residents from both models regarding their views of
      the CLPsych psychiatry experience. We also compared the scores on the Psychiatric
      Resident in Training Examination (PRITE). Lastly, we surveyed physicians who
      requested and received psychiatric consultations. RESULTS: Residents trained in
      the block CLPsych model reported a better education and clinical care compared
      longitudinal model. They also had better scores on the CLPsych section of the
      PRITE exam. Physicians receiving psychiatric consultations reported better
      overall quality of consults in the block model. CONCLUSIONS: It appears that
      block CL psychiatry experiences may be better than longitudinal ones. Programs
      should consider this design in psychiatry residency education.

PMID- 25398267
TI  - A Pathway to Freedom: An Evaluation of Screening Tools for the Identification of
      Trafficking Victims.
AB  - OBJECTIVES: Because training residents and faculty to identify human trafficking
      victims is a major public health priority, the authors review existing assessment
      tools. METHODS: PubMed and Google were searched using combinations of search
      terms including human, trafficking, sex, labor, screening, identification, and
      tool. RESULTS: Nine screening tools that met the inclusion criteria were found.
      They varied greatly in length, format, target demographic, supporting resources,
      and other parameters. Only two tools were designed specifically for healthcare
      providers. Only one tool was formally assessed to be valid and reliable in a
      pilot project in trafficking victim service organizations, although it has not
      been validated in the healthcare setting. CONCLUSIONS: This toolbox should
      facilitate the education of resident physicians and faculty in screening for
      trafficking victims, assist educators in assessing screening skills, and promote
      future research on the identification of trafficking victims.

PMID- 25398268
TI  - Concentrations of Cd, Pb, Mn and Zn in feathers and diet in heron chicks in
      Korea.
AB  - The feathers and diet items of grey heron (Ardea cinerea) and black-crowned night
      heron (Nycticorax nycticorax) chicks were collected at the Pyeongtaek colony,
      Korea in 2002 and 2008, and Cd, Pb, Mn and Zn concentrations were measured. Cd
      and Zn concentrations were higher in both species in 2008 than 2002 and were
      higher in grey herons than black-crowned night-herons in 2002. In 2008, Cd
      concentrations were higher in black-crowned night-herons than grey herons; Zn
      concentrations did not differ between species. Pb and Mn concentrations did not
      differ between species; however, there were yearly differences. Cd, Pb and Zn
      concentrations of feathers and diet were significantly correlated when species
      and years were combined. However, the predictive power of these relationships was
      limited because of species and yearly differences. All heron chicks had
      concentrations of Cd (<2 MUg/g dw) and Pb (<4 MUg/g dw) consistent with
      background concentrations for wild birds. Mn and Zn concentrations were within
      the range reported for other heron and egret species.

PMID- 25398269
TI  - Continuous measurement of cardiac output using pulse-contour analysis: truly beat
      to-beat?

PMID- 25398270
TI  - Surnames and social mobility in England, 1170-2012.
AB  - Using educational status in England from 1170 to 2012, we show that the rate of
      social mobility in any society can be estimated from knowledge of just two facts:
      the distribution over time of surnames in the society and the distribution of
      surnames among an elite or underclass. Such surname measures reveal that the
      typical estimate of parent-child correlations in socioeconomic measures in the
      range of 0.2-0.6 are misleading about rates of overall social mobility. Measuring
      education status through Oxbridge attendance suggests a generalized
      intergenerational correlation in status in the range of 0.70-0.90. Social status
      is more strongly inherited even than height. This correlation is unchanged over
      centuries. Social mobility in England in 2012 was little greater than in
      preindustrial times. Thus there are indications of an underlying social physics
      surprisingly immune to government intervention. 

PMID- 25398271
TI  - Sex differences in perceived risk and testing experience of HIV in an urban
      fishing setting in Ghana.
AB  - INTRODUCTION: Understanding sex differences in willingness to test and testing
      experience could aid the design of focus interventions to enhance uptake and
      engagement with care, treatment and support services. This study determined
      differences in perceived risk of acquiring HIV, willingness to test and HIV
      testing experience in an urban fishing community. METHODS: A cross-sectional
      community survey was conducted in 2013 among men and women in two fishing
      communities (Chorkor and James Town) in Accra. In all, 554 subjects (>= 18 years)
      were involved, 264 in Chorkor and 290 in James Town. Data on demographic
      characteristics, perceived risk for HIV and willingness to test for HIV and
      testing experience were collected with a structured questionnaire. Descriptive
      statistics and Chi square test were used for the analysis at 95% significant
      level, using SPSS version 21. RESULTS: Of 554 subjects, 329 (59.4%) were females,
      and median age was 32 years. Overall, only 91(40.4%) men and 118(35.9%) women
      perceived themselves to be at risk of acquiring HIV. A significant proportion of
      women were willing to test for HIV compared to men (86.3% vs. 80.0%, P = 0.048).
      Women were more likely to have ever tested for HIV compared to men (42.2% vs.
      28.6%, P = 0.001) and more women had tested within 12 months prior to survey than
      men (49.6% vs. 40.6%, P = 0.230). Of the number who had tested for HIV infection,
      a higher proportion of men tested voluntarily 42(65.6%), while a higher
      proportion of women tested as part of healthcare service received 96(69.1%); (P =
      0.001; indicating women vs. men). CONCLUSION: Sex differences in risk perception
      and willingness to test need more focused public education and behaviour change
      communication strategies to achieve high coverage. Community-based strategies
      could improve HIV testing among men whilst more access to testing in health
      settings should be available to women in these communities.

PMID- 25398272
TI  - A meta-analysis of the prevalence of Salmonella in food animals in Ethiopia.
AB  - BACKGROUND: The globalization of the food supply and the increased movements of
      people, animals and goods have increased the threat of Salmonella infections in
      several countries. The objective of this study was to estimate the prevalence of
      Salmonella in food animals in Ethiopia by using meta-analytical methods. RESULTS:
      The prevalence of Salmonella in slaughtered cattle, sheep, goats and pigs were
      7.07%, 8.41%, 9.01% and 43.81% respectively. The occurrence of Salmonella was
      significantly higher in pigs than in slaughtered true ruminants (p <0.001) but
      not significantly different between cattle, sheep and goats (p >0. 05). S.
      Mishmarhaemek, S. Infantis and S. Hadar were the predominant isolates in cattle,
      small ruminants and pigs respectively. S. Typhimurium was isolated from all host
      species. CONCLUSIONS: All food animals are considerable reservoirs of Salmonella
      and pose a significant risk to public health. Safety measures in slaughter houses
      and butcheries and education of the public could reduce the risk of transmission
      of Salmonella from animals to humans.

PMID- 25398273
TI  - Continuous decoding of movement intention of upper limb self-initiated analytic
      movements from pre-movement EEG correlates.
AB  - BACKGROUND: Brain-machine interfaces (BMI) have recently been integrated within
      motor rehabilitation therapies by actively involving the central nervous system
      (CNS) within the exercises. For instance, the online decoding of intention of
      motion of a limb from pre-movement EEG correlates is being used to convert
      passive rehabilitation strategies into active ones mediated by robotics. As early
      stages of upper limb motor rehabilitation usually focus on analytic single-joint
      mobilizations, this paper investigates the feasibility of building BMI decoders
      for these specific types of movements. METHODS: Two different experiments were
      performed within this study. For the first one, six healthy subjects performed
      seven self-initiated upper-limb analytic movements, involving from proximal to
      distal articulations. For the second experiment, three spinal cord injury
      patients performed two of the previously studied movements with their healthy
      elbow and paralyzed wrist. In both cases EEG neural correlates such as the event
      related desynchronization (ERD) and movement related cortical potentials (MRCP)
      were analyzed, as well as the accuracies of continuous decoders built using the
      pre-movement features of these correlates (i.e., the intention of motion was
      decoded before movement onset). RESULTS: The studied movements could be decoded
      in both healthy subjects and patients. For healthy subjects there were
      significant differences in the EEG correlates and decoding accuracies, dependent
      on the moving joint. Percentages of correctly anticipated trials ranged from 75%
      to 40% (with chance level being around 20%), with better performances for
      proximal than for distal movements. For the movements studied for the SCI
      patients the accuracies were similar to the ones of the healthy subjects.
      CONCLUSIONS: This paper shows how it is possible to build continuous decoders to
      detect movement intention from EEG correlates for seven different upper-limb
      analytic movements. Furthermore we report differences in accuracies among
      movements, which might have an impact on the design of the rehabilitation
      technologies that will integrate this new type of information. The applicability
      of the decoders was shown in a clinical population, with similar performances
      between healthy subjects and patients.

PMID- 25398275
TI  - Less than 10% of obese adults accept that they have a serious weight problem,
      survey finds.

PMID- 25398274
TI  - Behavioral and proteomic analysis of stress response in zebrafish (Danio rerio).
AB  - The purpose of this study is to determine the behavioral and proteomic
      consequences of shock-induced stress in zebrafish (Danio rerio) as a vertebrate
      model. Here we describe the behavioral effects of exposure to predictable and
      unpredictable electric shock, together with quantitative tandem mass tag isobaric
      labeling workflow to detect altered protein candidates in response to shock
      exposure. Behavioral results demonstrate a hyperactivity response to electric
      shock and a suppression of activity to a stimulus predicting shock. On the basis
      of the quantitative changes in protein abundance following shock exposure, eight
      proteins were significantly up-regulated (HADHB, hspa8, hspa5, actb1, mych4,
      atp2a1, zgc:86709, and zgc:86725). These proteins contribute crucially in
      catalytic activities, stress response, cation transport, and motor activities.
      This behavioral proteomic driven study clearly showed that besides the rapid
      induction of heat shock proteins, other catalytic enzymes and cation transporters
      were rapidly elevated as a mechanism to counteract oxidative stress conditions
      resulting from elevated fear/anxiety levels. 

PMID- 25398276
TI  - Curcumin does not switch melanin synthesis towards pheomelanin in B16F10 cells.
AB  - Melanin, the basic skin pigment present also in the majority of melanomas, has a
      huge impact on the efficiency of photodynamic, radio- or chemotherapies of
      melanoma. Moreover, the melanoma cells produce more melanin than normal
      melanocytes in adjacent skin do. Thus, attention has been paid to natural agents
      that are safe and effective in suppression of melanogenesis. B16F10 cells were
      studied by electron paramagnetic resonance (EPR) spectroscopy. The cells were
      cultured for 24-72 h in RPMI or DMEM with or without curcumin. The results
      confirmed that curcumin has no significant effect on B16F10 cells viability at
      concentrations of 1-10 uM. Curcumin at concentration of 10 uM significantly
      inhibited their proliferation and stimulated differentiation. We have not
      stimulated melanogenesis hormonally but we found a strong increase in
      melanogenesis in DMEM, containing more L-Tyr, as compared to RPMI. The EPR
      studies revealed that the effect of curcumin on melanogenesis in RPMI-incubated
      cells was not significant, and only in DMEM was curcumin able to inhibit
      melanogenesis. The effect of curcumin was only quantitative, as it did not switch
      eumelanogenesis towards pheomelanogenesis under any conditions. Interestingly, we
      observed elevation of production of hydrogen peroxide in DMEM-incubated cells, in
      parallel to the facilitation of melanogenesis. Curcumin significantly but
      transiently intensified the already pronounced generation of H2O2 in DMEM. We
      conclude that the quantitative effect of curcumin on melanogenesis in melanoma is
      intricate. It depends on the basic melanogenetic efficiency of the cells, and can
      be observed only in strongly pigmented cells. Qualitatively, curcumin does not
      switch melanogenesis towards pheomelanogenesis, either in strongly, or in weakly
      melanized melanoma cells.

PMID- 25398277
TI  - Stratification of Contemporary Patients Undergoing Radical Prostatectomy for High
      risk Prostate Cancer.
AB  - PURPOSE: Published data have shown heterogeneous outcomes for high-risk prostate
      cancer. Thus, we tried to identify more precise risk stratification system for
      contemporary high-risk prostate cancer. METHODS: Classifying patients according
      to National Comprehensive Cancer Network risk groups, we reviewed data of 1,905
      men who underwent radical prostatectomy (RP) at our institution from 2006 to
      2013. For our analyses, high-risk prostate cancers meeting at least one of two
      following factors were categorized as unfavorable high-risk prostate cancer:
      biopsy primary Gleason pattern 5 and/or multiple (>=2) high-risk criteria
      present. All other men with high-risk prostate cancer were designated as having
      favorable high-risk disease. Postoperative outcomes, including biochemical
      recurrence-free survivals were assessed and compared via log-rank test and Cox
      proportional hazards model. RESULTS: In multivariable analysis, primary Gleason 5
      pattern on biopsy (p = 0.008) and multiple (>=2) high-risk criteria (p < 0.001)
      were observed to be independent predictors of the risk of biochemical recurrence
      amongst high-risk group undergoing RP. Favorable high-risk prostate cancer group
      showed a significantly higher 5-year biochemical recurrence-free survival than
      unfavorable high-risk group (56.35 vs. 18.75 %; log-rank test: p < 0.001).
      Favorable high-risk group demonstrated significantly lower 5-year biochemical
      recurrence-free survival than intermediate-risk group (56.07 vs. 82.05 %; log
      rank test: p < 0.001). CONCLUSIONS: A significant heterogeneity existed in
      biochemical outcomes of contemporary patients with high-risk prostate cancer who
      underwent definitive RP. According to primary Gleason pattern and number of high
      risk criteria present, high-risk group should be stratified further into
      favorable and unfavorable disease.

PMID- 25398278
TI  - Prognostic significance of the lymph node ratio in stage IV colorectal cancer
      patients who have undergone curative resection.
AB  - BACKGROUND: The lymph node ratio (LNR) was proposed as a prognostic indicator in
      Stage III colorectal cancer (CRC) patients in recent studies. The purpose of this
      study was to evaluate the prognostic impact of the LNR in Stage IV CRC patients
      who have undergone curative resection. METHODS: A retrospective review of 119
      Stage IV CRC patients who underwent curative resection in our institute from 1997
      to 2009 was performed. Patients were divided into two groups (low LNR and high
      LNR) by means of their median LNR. A disease-free survival (DFS) and an overall
      survival (OS) were analyzed using the Kaplan-Meier curve; multivariate analysis
      was performed using the Cox proportional hazard model. RESULTS: The cutoff value
      for the LNR was 0.111. For the entire study group, the 5-year DFS was 22 % and
      the 5-year OS was 65 %. DFS was not significantly different between patients in
      the low LNR group and the high LNR group (25 and 19 %, respectively; P = 0.317),
      but OS was significantly higher in the low LNR group patients compared with the
      high LNR group patients (77 and 54 %, respectively; P < 0.001). Using
      multivariate analysis, we identified the LNR as an independent prognostic factor
      for OS, with a hazard ratio of 3.08 (95 % CI 1.38-8.19; P = 0.005). CONCLUSIONS:
      LNR is a potent prognostic indicator for stratification in Stage IV CRC patients
      who have undergone curative resection.

PMID- 25398279
TI  - Women's Impression of the Expected Breast Appearance and its Association with
      Breast Cancer Operations.
AB  - BACKGROUND: Significant concern exists from clinicians in all fields that rates
      of bilateral mastectomy and prophylactic mastectomy are increasing. This study
      was performed to evaluate women's perception of breast appearance and its
      association with breast cancer operations. METHODS: From April 2012 to May 2013,
      all women attending a breast clinic were shown two breast pictures, "natural" and
      "augmented," and asked which photograph represented the current expected
      appearance of breasts. Among breast cancer patients, the choice of breast cancer
      operation was correlated with picture selection. RESULTS: Of 1,177 consecutive
      women, mean age was 45 years. Overall, 70 % of patients felt that the augmented
      appearance is expected. This impression was seen in all racial/ethnic groups: non
      Hispanic White 65 %, African American 67 %, Hispanic 71 %, and other groups 70 %.
      Younger age was strongly associated with the augmented appearance (p < 0.0001).
      Patients older than age 60 years selected the augmented appearance only 51 % of
      the time. This percentage increased with each younger decade with patients
      younger than 40 years selecting the augmented appearance in 85 %. Among breast
      cancer patients, augmented appearance selection was more likely for patients who
      underwent reconstruction (92 %; p < 0.001), as well as for those undergoing
      bilateral mastectomy (74 %; p = 0.057) compared with mastectomy alone (49 %).
      CONCLUSIONS: Most women felt that the augmented appearance of breasts is
      currently expected, and this impression was more common in young women. This
      impression may be another factor contributing to the current trend of more
      extensive breast cancer operations and implant-based reconstructions.

PMID- 25398280
TI  - Cure model survival analysis after hepatic resection for colorectal liver
      metastases.
AB  - BACKGROUND: Statistical cure is achieved when a patient population has the same
      mortality as cancer-free individuals; however, data regarding the probability of
      cure after hepatectomy of colorectal liver metastases (CLM) have never been
      provided. We aimed to assess the probability of being statistically cured from
      CLM by hepatic resection. METHODS: Data from 1,012 consecutive patients
      undergoing curative resection for CLM (2001-2012) were used to fit a nonmixture
      cure model to compare mortality after surgery to that expected for the general
      population matched by sex and age. RESULTS: The 5- and 10-year disease-free
      survival was 18.9 and 15.8 %; the corresponding overall survival was 44.3 and
      32.7 %. In the entire study population, the probability of being cured from CLM
      was 20 % (95 % confidence interval 16.5-23.5). After the first year, the
      mortality excess of resected patients, in comparison to the general population,
      starts to decline until it approaches zero 6 years after surgery. After 6.48
      years, patients alive without tumor recurrence can be considered cured with 99 %
      certainty. Multivariate analysis showed that cure probabilities range from 40.9 %
      in patients with node-negative primary tumors and metachronous presentation of a
      single lesion <3 cm, to 1.5 % in patients with node positivity, and synchronous
      presentation of multiple, large CLMs. A model for the calculation of a cure
      fraction for each possible clinical scenario is provided. CONCLUSIONS: Using a
      cure model, the present results indicate that statistical cure of CLM is possible
      after hepatectomy; providing this information can help clinicians give more
      precise answer to patients' questions.

PMID- 25398281
TI  - Isolation of a novel beta-cypermethrin degrading strain Bacillus subtilis BSF01
      and its biodegradation pathway.
AB  - Continuous use of the pyrethroid insecticide beta-cypermethrin (beta-cp) has
      resulted in serious environmental contamination problems. We report here that a
      novel bacterial strain BSF01, which was isolated from activated sludge and
      identified as Bacillus subtilis (collection number: CCTCC AB 2014103), showed
      high efficiency in degrading beta-cp. Strain BSF01 was able to utilize beta-cp as
      the sole carbon source for growth and degraded 89.4 % of 50 mg L(-1) beta-cp
      within 7 days. The optimal conditions for beta-cp degradation were determined to
      be 34.5  degrees C, pH 6.7, and inocula amount 0.11 g dry wt L(-1) using response
      surface methodology. The kinetic parameters q max, K s, and K i were established
      to be 2.19 day(-1), 76.37 mg L(-1), and 54.14 mg L(-1), respectively. The
      critical inhibitor concentration was determined to be 64.30 mg L(-1). Seven
      metabolites were identified by gas chromatography-mass spectrometry. Furthermore,
      a novel biodegradation pathway for beta-cp was proposed on the basis of analysis
      of the metabolites. This strain was also capable of degrading a wide range of
      pyrethroid insecticides including cypermethrin, deltamethrin, cyhalothrin, and
      beta-cyfluthrin, which similar to beta-cp are hazardous chemicals. Taken
      together, our results depict the biodegradation pathway of beta-cp and highlight
      the promising potentials of strain BSF01 in bioremediation of pyrethroid
      contaminated environments.

PMID- 25398282
TI  - Bacillomycin L and surfactin contribute synergistically to the phenotypic
      features of Bacillus subtilis 916 and the biocontrol of rice sheath blight
      induced by Rhizoctonia solani.
AB  - The antagonistic activity of lipopeptides in Bacillus subtilis 916 has been well
      documented, yet relatively little is known about their mechanism in biofilm
      formation and environmental colonization. This study sought to examine the
      interaction of B. subtilis 916 on Rhizoctonia solani-infected rice sheath to
      elucidate the mechanism of colonization on plant leaves. Results showed that the
      mutants Deltabac, Deltasrf, and Deltasrf + bac of B. subtilis 916, deficient in
      bacillomycin L and surfactin production, respectively, not only altered colony
      morphology but also changed swarming motility, reduced antagonistic activity, and
      decreased biofilm formation. In particular, biofilm formation in mutant Deltabac,
      not Deltasrf or Deltasrf + bac, were restored with addition of surfactin and
      bacillomycin L at 10 and 50 MUg/mL, respectively. Moreover, surfactin and
      bacillomycin L were able to restore or enhance swarming motility in the
      corresponding mutants at 10 MUg/mL, respectively. With the aid of green
      fluorescent protein tagging, it was demonstrated that B. subtilis 916 formed a
      robust biofilm on the rice sheath blight lesion and colonized well on R. solani
      infected rice sheath, while its corresponding mutants performed poorly. These
      observations also correlated with the rice cultivar pot experiments, in which B.
      subtilis 916 exhibited greater biocontrol than its mutants. Our results suggest
      that surfactin and bacillomycin L contribute differently but synergistically to
      the biocontrol of rice sheath blight in B. subtilis 916 through its antifungal
      activity, biofilm formation, and colonization. 

PMID- 25398284
TI  - Distribution and environmental significance of nitrite-dependent anaerobic
      methane-oxidising bacteria in natural ecosystems.
AB  - Nitrite-dependent anaerobic methane oxidation (N-DAMO) is a recently discovered
      process that is performed by "Candidatus Methylomirabilis oxyfera" (M. oxyfera).
      This process constitutes a unique association between the two major global
      elements essential to life, carbon and nitrogen, and may act as an important and
      overlooked sink of the greenhouse gas methane. In recent years, more and more
      studies have reported the distribution of M. oxyfera-like bacteria and the
      occurrence of N-DAMO process in different natural ecosystems, including
      freshwater lakes, rivers, wetlands and marine ecosystems. Previous studies have
      estimated that a total of 2%-6% of current worldwide methane flux in wetlands
      could be consumed via the N-DAMO process. These findings indicate that N-DAMO is
      indeed a previously overlooked methane sink in natural ecosystems. Given the
      worldwide increase in anthropogenic nitrogen pollution, the N-DAMO process as a
      methane sink in reducing global warming could become more important in the
      future. The present mini-review summarises the current knowledge of the
      ecological distribution of M. oxyfera-like bacteria and the potential importance
      of the N-DAMO process in reducing methane emissions in various natural
      ecosystems. The potential influence of environmental factors on the N-DAMO
      process is also discussed.

PMID- 25398283
TI  - Bacillus subtilis as heterologous host for the secretory production of the non
      ribosomal cyclodepsipeptide enniatin.
AB  - The heterologous expression of genes or gene clusters in microbial hosts,
      followed by metabolic engineering of biosynthetic pathways, is key to access
      industrially and pharmaceutically relevant compounds in an economically
      affordable and sustainable manner. Therefore, platforms need to be developed,
      which provide tools for the controlled synthesis of bioactive compounds. The Gram
      positive bacterium Bacillus subtilis is a promising candidate for such
      applications, as it is generally regarded as a safe production host, its
      physiology is well investigated and a variety of tools is available for its
      genetic manipulation. Furthermore, this industrially relevant bacterium provides
      a high secretory potential not only for enzymes but also for primary and
      secondary metabolites. In this study, we present the first heterologous
      expression of an eukaryotic non-ribosomal peptide synthetase gene (esyn) coding
      for the biosynthesis of the small molecule enniatin in B. subtilis. Enniatin is a
      pharmaceutically used cyclodepsipeptide for treatment of topical bacterial and
      fungal infections. We generated various enniatin-producing B. subtilis strains,
      allowing for either single chromosomal or plasmid-based multi-copy expression of
      the esyn cluster under the control of an acetoin-inducible promoter system.
      Optimization of cultivation conditions, combined with modifications of the
      genetic background and multi-copy plasmid-based esyn expression, resulted in a
      secretory production of enniatin B. This work presents B. subtilis as a suitable
      host for the expression of heterologous eukaryotic non-ribosomal peptide
      synthetases (NRPS) clusters. 

PMID- 25398286
TI  - Analyzing the revolution of anaerobic ammonium oxidation (anammox) performance
      and sludge characteristics under zinc inhibition.
AB  - In the present study, the short- and long-term effects of Zn(II) on the anaerobic
      ammonium oxidation (anammox) performance and sludge characteristics were
      evaluated. The anammox activity decreased with increasing Zn(II) concentration
      and pre-exposure time in short-term tests. The half maximal inhibitory
      concentration (IC50) of Zn(II) was found to be 25.0 mg L(-1). The 24 and 48-h pre
      exposure time was a restricted factor impacting the anammox activity, and washing
      the inhibited sludge with buffer solution only worked under 0 and 24-h pre
      exposure time. The anammox sludge could tolerate 5 mg L(-1) Zn(II) but was
      suppressed at 8 mg L(-1). The inhibited performance could be remitted, as the
      combination strategies were applied, and after the short term of recovery period,
      the inhibited sludge characteristics were remitted to the normal.

PMID- 25398285
TI  - Isolation, sequencing, and heterologous expression of the Paecilomyces variotii
      gene encoding S-hydroxymethylglutathione dehydrogenase (fldA).
AB  - The filamentous fungus Paecilomyces variotii NBRC 109023 (teleomorph:
      Byssochlamys spectabilis NBRC 109023) degrades formaldehyde at concentrations as
      high as 2.4 % (w/v). In many prokaryotes and in all known eukaryotes,
      formaldehyde degradation is catalyzed by S-hydroxymethylglutathione (S-HMGSH)
      dehydrogenase. We report here the isolation and characterization of the gene
      encoding S-HMGSH dehydrogenase activity in P. variotii. The 1.6-kb fldA gene
      contained 5 introns and 6 exons, and the corresponding cDNA was 1143 bp, encoding
      a 40-kDa protein composed of 380 amino acids. FldA was predicted to have 74.3,
      73.7, 68.5, and 67.4 % amino acid identity to the S-HMGSH dehydrogenases of
      Hansenula polymorpha, Candida boidinii, Saccharomyces cerevisiae, and
      Kluyveromyces lactis, respectively. The predicted protein also showed high amino
      acid similarity (84~86 %) to the products of putative fldA genes from other
      filamentous fungi, including Aspergillus sp. and Penicillium sp. Notably, the P.
      variotii fldA gene was able to functionally complement a Saccharomyces cerevisiae
      strain (BY4741 ?sfa1) lacking the gene for S-HMGSH dehydrogenase. The
      heterologous expression construct rendered BY4741 ?sfa1 tolerant to exogenous
      formaldehyde. Although BY4741 (parental wild-type strain) was unable to degrade
      even low concentrations of formaldehyde, BY4741 ?sfa1 harboring Paecilomyces fldA
      was able to degrade 4 mM formaldehyde within 30 h. The findings from this study
      confirm the essential role of S-HMGSH dehydrogenase in detoxifying formaldehyde. 

PMID- 25398287
TI  - Degradation of ethyl mercaptan and its major intermediate diethyl disulfide by
      Pseudomonas sp. strain WL2.
AB  - A Pseudomonas sp. strain WL2 that is able to efficiently metabolize ethyl
      mercaptan (EM) into diethyl disulfide (DEDS) through enzymatic oxidation was
      isolated from the activated sludge of a pharmaceutical wastewater plant. One
      hundred percent removal of 113.5 mg L(-1) EM and 110.3 mg L(-1) DEDS were
      obtained within 14 and 32 h, respectively. A putative EM degradation pathway that
      involved the catabolism via DEDS was proposed, which indicated DEDS were further
      mineralized into carbon dioxide (CO2), bacterial cells, and sulfate (SO4 (2-))
      through the transformation of element sulfur and ethyl aldehyde. Degradation
      kinetics for EM and DEDS with different initial concentrations by strain WL2 were
      evaluated using Haldane-Andrews model with maximum specific degradation rates of
      3.13 and 1.33 g g(-1) h(-1), respectively, and maximum degradation rate constants
      of 0.522 and 0.175 h(-1) using pseudo-first-order kinetic model were obtained.
      Results obtained that aerobic degradation of EM by strain WL2 was more efficient
      than those from previous studies. Substrate range studies of strain WL2
      demonstrated its ability to degrade several mercaptans, disulfides, aldehydes,
      and methanol. All the results obtained highlight the potential of strain WL2 for
      the use in the biodegradation of volatile organic sulfur compounds (VOSCs).

PMID- 25398289
TI  - Intrauterine device may trigger typical attacks of familial Mediterranean fever:
      a case report.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disorder
      characterized by episodic, recurrent, self-limited attacks of fever and serositis
      (sterile peritonitis, pleuritis, arthritis, etc). The insufficiency in
      restriction of mild inflammation contributes this consequence in FMF.Intrauterine
      devices (IUDs) have been widely used in the world for contraception by
      gynecologists as an effective and safe method. Herein, we present a woman with
      FMF as the first case, whose attacks were triggered by copper-containing IUD. Our
      hypothesis in the present case was that sterile mild inflammation in the uterus
      caused by copper-containing IUD may be the initial source of systemic
      inflammatory response.In our opinion, clinicians should consider that the copper
      containing IUDs may be another cause of FMF attacks in women using this
      contraceptive method. 

PMID- 25398288
TI  - The major predictors of amputation and length of stay in diabetic patients with
      acute foot ulceration.
AB  - BACKGROUND: Diabetic foot infections are associated with substantial morbidity
      and mortality. Prediction of diabetic foot ulcer outcome may be helpful for
      optimizing management strategy. This study aimed to determine the major
      predictors of amputation and length of stay in diabetic patients with acute foot
      ulceration. METHODS: A total of 55 type 2 diabetic patients with diabetic foot
      infection were enrolled. The patients were evaluated according to the Infectious
      Diseases Society of America and International Working Group on the Diabetic Foot
      criteria and also the Wagner's classification. Blood samples were taken at the
      start of hospitalization for the measurement of glucose, hemoglobin A1C (HbA1C),
      white blood cells (WBC), C-reactive protein (CRP), and erythrocyte sedimentation
      rate (ESR). Length of stay in hospital was recorded. RESULTS: WBC and CRP were
      significantly higher in lower-extremity amputation (LEA) group (p = 0.001 and p =
      0.008, respectively); also, ESR was higher in this group, but there was no
      statistical significance. Wagner grade and infection severity were significantly
      higher in the LEA group as compared with the non-LEA group (both p values <
      0.001). Glycemic control parameters (i.e., HbA1C, plasma glucose) were not
      different in LEA and non-LEA groups. In correlation analyses, amputation rate was
      negatively correlated (r = - 0.512, p < 0.001) with length of stay. WBC, ESR,
      CRP, Wagner grade, and severity of infection showed positive correlation with
      length of stay (r = 0.493, p < 0.001; r = 0.271, p = 0.045; r = 0.299, p = 0.027;
      r = 0.434, p = 0.001; and r = 0.464, p < 0.001, respectively). CONCLUSIONS:
      Baseline levels of acute-phase reactants, especially CRP, WBC, ESR, and increased
      Wagner grade, appeared to be helpful in predicting amputation and length of stay
      in diabetic patients with acute foot ulceration. However, duration of diabetes
      and glucose control seems to have no effect.

PMID- 25398290
TI  - Spinal subdural hematoma following lumbar decompressive surgery: a report of two
      cases.
AB  - Spinal subdural hematoma (SSDH) following spine surgery is an extremely rare
      condition, with only three cases being reported in the literature. Unintended
      durotomy has been associated with SSDH due to alterations of pressures in the
      dural compartments. The objective of the present report was to report two rare
      cases of acute SSDH developed after lumbar decompressive surgery. In one of the
      patients, the diagnosis of SSDH was followed by urgent hematoma evacuation via
      durotomy due to the patient's worsening neurological symptoms. In the second
      patient, the SSDH was treated conservatively due to the absence of severe or
      progressive motor or sensory deficits. In conclusion, emergency evacuation via
      durotomy is the treatment of choice for patients with SSDH and neurologic
      impairment. Conservative management may be indicated in selected cases with
      absent motor and sensory deficits. 

PMID- 25398291
TI  - A pain in the throat: a 19-year history of symptoms relating to the carotid
      artery.
AB  - A 38-year-old man presented with a 19-year history of sore throat and an ache
      radiating from the centre of the anterior neck to the both ears and the occiput.
      Computed tomography angiography revealed a tortuous submucosal right internal
      carotid artery, which was causing tonsillar displacement. The diagnosis of
      carotidynia has a controversial history within the literature and is currently
      not accepted as a distinct pathological entity by the International Headache
      Society. In this patient, the clinical and imaging features, in addition to the
      absence of any other pathology confers support to the diagnosis of carotidynia. 

PMID- 25398292
TI  - Ki-67 proliferation index in patients with placenta previa percreta in the third
      trimester.
AB  - AIM: The purpose of this study was to investigate proliferative capacity of
      placenta previa percreta in the third trimester via evaluating Ki-67
      proliferating index. METHODS: The paraffin blocks of placental tissues, which
      were obtained from the patients who underwent hysterectomy for placenta previa
      percreta (n = 12, gestational age > 28 weeks), from legal abortions (n = 12,
      gestational age < 10 weeks), and of cesarean deliveries with the indication of
      previous cesarean section, without any complication (n = 12, gestational age > 38
      weeks), between January 2011 and April 2013, were included into the study. The
      paraffin blocks of the patients were stained with Ki-67 (proliferating cell
      marker) immunohistochemically, and Ki-67 proliferation index levels were
      calculated. RESULTS: Ki-67 proliferation index levels were higher in patients
      with legal abortions than patients with placenta percreta or noncomplicated
      cesarean delivery group. However, any statistically significant difference was
      not detected between the percreta and noncomplicated groups (p > 0.05).
      CONCLUSION: The tissue samples of the patients with placenta previa percreta
      exhibited low proliferative capacity similar to the samples of normal
      placentation group.

PMID- 25398293
TI  - Fontan-like circulation as a criterion for heart transplantation in
      arrhythmogenic right ventricular dysplasia.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is often associated
      with progressive right ventricular dysfunction. Although heart transplantation
      (HTx) is suggested in these patients, indication and optimal timing for listing
      can be challenging. METHODS AND RESULTS: The study comprises four patients (two
      male, range: 37-56 years) with advanced ARVD who were considered for HTx.
      Standard inclusion criteria for HTx listing such as clinical signs, New York
      Heart Association (NYHA) classification (II-III), and N-terminal pro-brain
      natriuretic peptide (NT-proBNP) (3672 +/- 1407 pg/ml) were heterogeneous and did
      not add unequivocally to decision making. In all patients, though, right heart
      hemodynamics revealed Fontan-like circulation (FLC) with equilibrated pressure
      tracings between the right atrium (16 +/- 4 mmHg) and the pulmonary artery (16 +/
      5 mmHg). In this condition, the pulmonary blood flow can be regarded as nearly
      non-pulsatile, as it is passive and propelled by the transpulmonary gradient and
      intrathoracic pressure alterations produced by breathing to the left atrium.
      Based on these findings, all patients were listed for HTx and were finally
      successfully transplanted. CONCLUSIONS: In patients with ARVD, evidence of FLC
      may serve as an additional criterion for HTx. This applies particularly to
      patients who do not clearly fulfill standard transplant criteria and to patients
      with electrical instability.

PMID- 25398295
TI  - The introduction of novel oral anticoagulants in 2009 has been rightly heralded
      as a major therapeutic breakthrough.

PMID- 25398294
TI  - Off-pump myocardial revascularization attenuates endothelin-1 expression in
      systemic, pulmonary, and coronary circulation.
AB  - OBJECTIVE: The objective of this study was to evaluate the influence of
      cardiopulmonary bypass (CPB) on endothelin-1 (ET-1) expression in various
      circulation compartments in patients undergoing myocardial revascularization.
      METHODS: A total of 30 patients were randomized to undergo myocardial
      revascularization with (CABG, n = 15) or without (OPCAB, n = 15) CPB. Samples
      were taken preoperatively, after establishing CPB and after CPB (CABG group),
      prior to and after revascularization (OPCAB group), and 6 and 24 h
      postoperatively. Values of ET-1 were compared between groups at all time points
      and correlated with postoperative cardioselective enzyme values and clinical
      parameters. RESULTS: In OPCAB group, ET-1 levels did not significantly vary
      between time points. In CABG group, ET-1 levels were significantly elevated vs.
      baseline in arterial: ART-T2 vs. ART-T0 (1.83 +/- 1.81 vs. 0.76 +/- 1.07 fmol/mL,
      p = 0.05), pulmonary: SG-T2 vs. SG-T0 (2.70 +/- 2.75 vs. 0.39 +/- 0.28 fmol/mL, p
      < 0.001) and SG-T3 vs. SG-T0 (1.56 +/- 0.28 vs. 0.39 +/- 0.28 fmol/mL, p <
      0.001), and coronary circulation CS-T2 vs. CS-T1 (1.12 +/- 0.49 vs. 0.27 +/- 0.09
      fmol/mL, p = 0.01). ET-1 levels were significantly higher in CABG group in all
      vascular compartments: ART-T2 (1.83 +/- 1.81 vs. 0.17 +/- 0.16 fmol/mL, p =
      0.02), ART-T4 (0.99 +/- 0.56 vs. 0.24 +/- 0.12 fmol/mL, p = 0.01), SG-T1 (0.59 +/
      0.15 vs. 0.25 +/- 0.13 fmol/mL, p = 0.01), SG-T2 (2.70 +/- 2.75 vs. 0.30 +/-
      0.24 fmol/mL, p = 0.004), SG-T3 (1.56 +/- 0.28 vs. 0.35 +/- 0.31 fmol/mL, p <
      0.001), SG-T4 (1.34 +/- 0.11 vs. 0.34 +/- 0.16 fmol/mL, p < 0.001), and CS-T2
      (1.12 +/- 0.49 vs. 0.12 +/- 0.12 fmol/mL, p = 0.004). Coronary sinus ET-1 level
      after CPB (CS-T2) in CABG group correlated positively with troponin-I level 24 h
      postoperatively (r(2) = 0.802, p = 0.02) CONCLUSION: Off-pump myocardial
      revascularization attenuates ET-1 expression in all investigated vascular
      compartments. Elevated coronary ET-1 levels after CPB in CABG group correlate
      with troponin-I levels 24 h postoperatively.

PMID- 25398297
TI  - Intestinal bacterial metabolism and anti-complement activities of three major
      components of the seeds of Entada phaseoloides.
AB  - The present study aimed to investigate the metabolism of Entadae Semen by human
      fecal bacteria to clarify the relationship between its pharmacological activities
      and intestinal metabolism. Three major components (phaseoloidin, entadamide A
      beta-D-glucopyranoside and entadamide A) were isolated and identified from
      Entadae Semen and then incubated with human fecal microflora in vitro to
      investigate the metabolic processes. The metabolites were analyzed with high
      performance liquid chromatography (HPLC). The anti-complement activities of the
      three components and their metabolites produced by human fecal microflora were
      evaluated in vitro using a hemolysis assay. Phaseoloidin and entadamide A-beta-D
      glucopyranoside were metabolized into their respective aglycones during the
      incubation process, which enhanced their anti-complement effects. These results
      indicated that the presence of intestinal bacteria likely plays an important role
      and that the pharmacological effects of Entadae Semen may be dependent on
      intestinal bacterial metabolism. 

PMID- 25398298
TI  - New maltol glycosides from Flos Sophorae.
AB  - Three new maltol glycosides, designated soyamalosides A (1), B (2), and C (3),
      together with eight known compounds (4-11), were obtained from a 70 % EtOH
      extract of Flos Sophorae. Their structures were elucidated by chemical and
      spectroscopic methods. Of the known compounds, this is the first report of 4-6,
      9, and 11 in the Sophora genus. Compounds 2, 3, and 10 showed significant
      protective effects against antimycin A-induced L6 cell injury. 

PMID- 25398301
TI  - Vitamin E supplementation and mortality in healthy people: a meta-analysis of
      randomised controlled trials.
AB  - PURPOSE: To evaluate the effect of oral vitamin E supplementation on all-cause
      mortality in apparently healthy people. METHODS: A systematic review and meta
      analysis was conducted on randomised controlled trials (RCTs) with >= 6 months of
      follow up investigating the effect of vitamin E supplementation on healthy adults
      in developed countries. Electronic databases (MEDLINE, EMBASE, and Cochrane
      Central Register of Controlled Trials) and reference lists of trial reports were
      searched for RCTs published between 1966 and June 2012. Three investigators
      assessed eligibility of identified trials. Disagreements were resolved by
      consensus. Two investigators independently extracted data according to the
      criteria. RESULTS: There were 18 RCTs identified with 142,219 apparently healthy
      participants (71,116 in vitamin E intervention groups and 71,103 in control
      groups) that were included in the final analysis. Fixed effect and random effects
      analysis of the 18 trials revealed that supplementation with vitamin E was not
      associated with all-cause mortality (relative risk 1.01, 95% confidence interval
      0.97 - 1.05, p = 0.65). Subgroup analyses by type of vitamin E (natural or
      synthetic), dose or duration of exposure, study design or quality, and pre
      specified mortality outcome showed no association with all-cause mortality.
      CONCLUSIONS: The evidence from pooled analysis of 18 randomised controlled trials
      undertaken in apparently healthy people shows no effect of vitamin E
      supplementation at a dose of 23-800 IU/day on all-cause mortality.

PMID- 25398299
TI  - Emotions in reading: Dissociation of happiness and positivity.
AB  - The hierarchical emotion model proposed by Panksepp (1998) predicts that
      affective processing will rely on three functionally and neuroanatomically
      distinct levels, engaging subcortical networks (primary level), the limbic system
      (secondary level), and the neocortex (tertiary level). In the present fMRI study,
      we manipulated happiness and positivity, which are assumed to rely on secondary-
      and tertiary-level processes, respectively, to test these assumptions in a word
      recognition task. In accordance with the model predictions, evidence for a double
      dissociation was found in the brain activation patterns: Secondary-level
      processes engaged parts of the limbic system-specifically, the right hemispheric
      amygdala. Tertiary-level processes, in contrast, relied predominantly on frontal
      neocortical structures such as the left inferior frontal and medial frontal gyri.
      These results are interpreted as support for Panksepp's (1998) model and as an
      indicator of a semantic foundation of affective dimensions. 

PMID- 25398302
TI  - Fungal transformation of androsta-1,4-diene-3,17-dione by Aspergillus
      brasiliensis.
AB  - BACKGROUND: The biotransformation of steroids by fungal biocatalysts has been
      recognized for many years. There are numerous fungi of the genus Aspergillus
      which have been shown to transform different steroid substances. The possibility
      of using filamentous fungi Aspergillus brasiliensis cells in the
      biotransformation of androsta-1,4-diene-3,17-dione, was evaluated. METHODS: The
      fungal strain was inoculated into the transformation medium which supplemented
      with androstadienedione as a substrate and fermentation continued for 5 days. The
      metabolites were extracted and isolated by thin layer chromatography. The
      structures of these metabolites were elucidated using (1)H-NMR, broadband
      decoupled (13)C-NMR, EI Mass and IR spectroscopies. RESULTS: The fermentation
      yielded one reduced product: 17beta-hydroxyandrost-1,4-dien-3-one and two
      hydroxylated metabolites: 11alpha-hydroxyandrost-1,4-diene-3,17-dione and 12beta
      hydroxyandrost-1,4-diene-3,17-dione. CONCLUSIONS: The results obtained in this
      study show that A. brasiliendsis could be considered as a biocatalyst for
      producing important derivatives from androstadienedione.

PMID- 25398303
TI  - Treatment effects of removable functional appliances in patients with Class II
      malocclusion: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the treatment effects of removable functional appliances
      (RFAs) in treated versus untreated patients with Class II malocclusion by means
      of lateral cephalometric radiographs. SEARCH METHODS: Unrestricted electronic
      search of 18 databases and manual searches up to October 2013. SELECTION
      CRITERIA: Prospective randomized and non-randomized controlled trials reporting
      on cephalometric angular measurements of Class II patients treated with RFAs and
      their matched controls. DATA COLLECTION AND ANALYSIS: Skeletal, dental, and soft
      tissue changes were annualized and stratified to short- and long-term effects.
      Methodological limitations were evaluated with the Cochrane Risk of Bias tool and
      the Downs and Black checklist. Mean differences (MDs) with their 95% confidence
      intervals (CIs) were calculated from random-effects meta-analyses. Patient- or
      appliance-related subgroup analyses and sensitivity analyses were performed with
      mixed-effects models. RESULTS: Seventeen studies were included (1031 patients;
      mean age: 10.6 years), with most of them originating from university clinics and
      reporting short-term effects (directly after the removal of RFAs). Treatment was
      associated with minimal reduction of SNA angle (11 studies, MD = -0.28
      degree/year, 95% CI: -0.44 to -0.12 degree/year), minimal increase of SNB angle
      (11 studies, MD = 0.62 degree/year, 95% CI: 0.36-0.88 degree/year), and small
      decrease of ANB angle (10 studies, MD = -1.14 degree/year, 95% CI: -1.52 to -0.77
      degree/year) compared to untreated Class II patients. RFAs caused significant
      dentoalveolar changes (predominantly retroclination of the upper incisors) and
      significant soft tissue changes. Skeletal changes were more pronounced with the
      Twin Block appliance. Various patient- or appliance-related factors influenced
      the results of the subgroup analyses, while the sensitivity analyses indicated
      robustness. Existing evidence was inadequate to assess the long-term
      effectiveness of RFAs. CONCLUSIONS: The short-term evidence indicates that RFAs
      are effective in improving Class II malocclusion, although their effects are
      mainly dentoalveolar, rather than skeletal.

PMID- 25398305
TI  - Positive fluid balance and AKI diagnosis: assessing the extent and duration of
      'creatinine dilution'.

PMID- 25398306
TI  - Ten things you need to know to practice neurological critical care.

PMID- 25398304
TI  - Prognostication in comatose survivors of cardiac arrest: an advisory statement
      from the European Resuscitation Council and the European Society of Intensive
      Care Medicine.
AB  - OBJECTIVES: To review and update the evidence on predictors of poor outcome
      (death, persistent vegetative state or severe neurological disability) in adult
      comatose survivors of cardiac arrest, either treated or not treated with
      controlled temperature, to identify knowledge gaps and to suggest a reliable
      prognostication strategy. METHODS: GRADE-based systematic review followed by
      expert consensus achieved using Web-based Delphi methodology, conference calls
      and face-to-face meetings. Predictors based on clinical examination,
      electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS:
      Evidence from a total of 73 studies was reviewed. The quality of evidence was low
      or very low for almost all studies. In patients who are comatose with absent or
      extensor motor response at >= 72 h from arrest, either treated or not treated
      with controlled temperature, bilateral absence of either pupillary and corneal
      reflexes or N20 wave of short-latency somatosensory evoked potentials were
      identified as the most robust predictors. Early status myoclonus, elevated values
      of neuron-specific enolase at 48-72 h from arrest, unreactive malignant EEG
      patterns after rewarming, and presence of diffuse signs of postanoxic injury on
      either computed tomography or magnetic resonance imaging were identified as
      useful but less robust predictors. Prolonged observation and repeated assessments
      should be considered when results of initial assessment are inconclusive.
      Although no specific combination of predictors is sufficiently supported by
      available evidence, a multimodal prognostication approach is recommended in all
      patients.

PMID- 25398307
TI  - Comments on Baranwal et al: dexamethasone pretreatment for 24 h versus 6 h for
      prevention of postextubation airway obstruction in children.

PMID- 25398308
TI  - Feasibility and performance of lymphoscintigraphy in sentinel lymph node biopsy
      for early cervical cancer: results of the prospective multicenter SENTICOL study.
AB  - OBJECTIVE: To evaluate feasibility, SLN detection rate, and SLN location of
      lymphoscintigraphy in sentinel lymph node (SLN) biopsy for early cervical cancer.
      METHODS: Ancillary analysis of data from the multicenter prospective SENTICOL
      study (January 2005-June 2007) of patients with early cervical cancer (FIGO stage
      IA with emboli to IB1) was conducted. Preoperative lymphoscintigraphy was
      performed after intracervical administration of 60 or 120 MBq of (99m)Tc-labeled
      radiocolloid on the day before (long protocol) or morning of (short protocol)
      surgery. SLNs were identified intraoperatively using combined
      radioactivity/patent blue detection. SLNs were sampled electively and routine
      bilateral pelvic lymphadenectomy was performed by laparoscopy. A centralized
      review of lymphoscintigraphies was performed to assess feasibility, detection
      rates, and anatomic SLN location. RESULTS: Of 139 patients included in the
      SENTICOL study, 133 received radiocolloid injection, and 131 (98.5 %) underwent
      preoperative lymphoscintigraphy, with the long protocol in three-fourths of
      cases. The lymphoscintigraphic detection rate was 87.8 %, with a median of 2 (1
      4) SLNs per patient. By multivariate analysis, factors independently associated
      with lymphoscintigraphic SLN detection were age [odds ratio (OR) 0.91, 95 %
      confidence interval (95 % CI) 0.87-0.96; P < 0.001], and protocol (long vs.
      short; OR 8.23, 95 % CI 1.87-36.25; P = 0.005). Bilateral SLN identification by
      lymphoscintigraphy occurred in 67 % of cases and was independently influenced by
      age (OR 0.95, 95 % CI 0.92-0.98, P < 0.001) and protocol (OR 5.42, 95 % CI 2.21
      13.27; P < 0.001). Although 60.5 % of preoperative SLNs were in the external
      iliac territory, unusual drainage patterns included the common iliac (19.6 %),
      para-aortic (10.8 %), and parametrial (6 %) basins. CONCLUSIONS: Our study
      demonstrates the feasibility and good detection rate of preoperative
      lymphoscintigraphy, with better detection in younger patients and with the long
      protocol. The high proportion of SLN basins in unexpected territories is of
      interest to guide intraoperative detection. Further studies are needed to better
      evaluate preoperative detection and to assess the contribution of
      lymphoscintigraphy to intraoperative detection.

PMID- 25398309
TI  - Axillary lymph node staging in breast cancer: clinical value of single photon
      emission computed tomography-computed tomography (SPECT-CT) with 99mTc
      methoxyisobutylisonitrile.
AB  - OBJECTIVE: To determine diagnostic accuracy of SPECT, CT and SPECT-CT in axillary
      lymph node (LN) staging in breast cancer (BC). METHODS: Sixty consecutive
      patients with primary operable T1-3NxM0 BC were included in this study. All
      patients underwent SPECT-CT examination on Symbia-T16 scanner which consists of
      dual-head gamma camera combined with 16 slices diagnostic CT. SPECT-CT
      acquisition started 10-15 min after i/v injection of 740-1,000 MBq of 99mTc-MIBI.
      On CT images of axillary LN we analyzed following diagnostic signs: size (short
      axis more or less than 10 mm), shape (round or oval), cortical thickness and fat
      content (solid or with fat gate). Intensity of tracer uptake in axillary LN was
      classified as follows: grade (Gr) I-background, Gr II-slightly above background,
      Gr III-intense but below uptake in muscles, Gr IV-as high as in muscles.
      Histological examination of dissected LN was used as gold standard. RESULTS:
      Various combinations of CT signs of axillary LN involvement demonstrated moderate
      diagnostic value with best results characterized by low (55 %) sensitivity (SEN),
      97 % specificity (SP) and 83 % accuracy (AC). Intensive (Gr IV) uptake of 99mTc
      MIBI in axillary LN characterized by low (55 %) SEN, high (100 %) SP and moderate
      (84 %) AC. Combination of CT and SPECT signs looks most promising especially when
      LN metastases were diagnosed in patients with enlarged solid LN or normal sized
      LN with Gr III-IV 99Tc-MIBI uptake. In these cases, SEN was equal to 75 %, SP-90
      %, AC-85 %, only one of 5 patients with false negative results had metastases in
      more than 2 LN. CONCLUSIONS: By combination of SPECT and CT data we can more
      accurately diagnose axillary LN invasion by breast cancer.

PMID- 25398310
TI  - F-18 fluorodeoxyglucose PET angiography of the abdominal arteries: evaluation of
      image quality and comparison with contrast-enhanced CT.
AB  - OBJECTIVE: Positron emission tomography (PET) angiography utilizes early dynamic
      PET acquisitions for depiction of the arterial vasculature. The aim of this study
      was to assess image quality and to evaluate feasibility of F-18 FDG PET
      angiography of the abdominal arteries. METHODS: Twenty-seven patients were
      included in the study. Standard activities of 250-280 MBq F-18 FDG were
      administered. Early dynamic PET data were acquired in list mode. Time frames of 6
      * 10 s after tracer injection were reconstructed. Images were analyzed in MPR and
      MIP modes. Image quality was scored according to scale from 1 to 4. PET
      angiography findings were compared with contrast-enhanced CT imaging. RESULTS:
      All examinations were completed successfully. In 83 % of cases, best arterial
      contrast was seen between 10 and 40 s after tracer injection. Good or moderate
      diagnostic image quality of the aorta was noted in all the cases, with a 100 %
      negative predictive value of a normal finding. Celiac trunks, renal and superior
      mesenteric arteries could be visualized with limited image quality, good to
      excellent negative predictive values of 90-100 %, and low positive predictive
      values of 3-13 % due to overestimation of arterial occlusive disease and false
      positive findings. CONCLUSIONS: F-18 FDG PET angiography is technically feasible
      and can exclude relevant abdominal aortic occlusive disease. Clinical use in the
      evaluation of smaller arteries of the upper abdomen is limited. The main
      advantages of PET angiography are the absence of acute risks to the patient and
      the possibility to acquire the data as part of routine PET/CT studies.

PMID- 25398311
TI  - A survey of manufacturing and handling practices for monoclonal antibodies by
      pharmacy, nursing and medical personnel.
AB  - INTRODUCTION: There is a paucity of data available to assess the occupational
      health and safety risk associated with exposure to monoclonal antibodies.
      Industry standards and published guidelines are conflicting or outdated.
      Guidelines offer contrary recommendations based on an array of methodological
      approaches. This survey aimed to describe current practices, beliefs and
      attitudes relating to the handling of monoclonal antibodies by Australian
      medical, nursing and pharmacy clinicians. METHODS: An electronic survey was
      distributed between June and September 2013. Respondents were surveyed on three
      focus areas: institutional guideline availability and content, current practices
      and attitudes. Demographic data relating to respondent and primary place of
      practice were also collected. RESULTS: A total of 222 clinicians completed the
      survey, with representation from all targeted professional groups and from a
      variety of geographic locations. 92% of respondents reported that their
      institution prepared or administered monoclonal antibodies, with 87% specifically
      handling anti-cancer monoclonal antibodies. Monoclonal antibodies were mostly
      prepared onsite (84-90%) and mostly within pharmacy clean-rooms (75%) and using
      cytotoxic cabinets (61%). 43% of respondents reported access to institutional
      monoclonal antibody handling guidelines with risk reduction strategies including
      training and education (71%), spill and waste management (71%), procedures for
      transportation (57%) and restricted handling (50%). Nurses had a stronger
      preference towards pharmacy manufacturing than both doctors and pharmacists for a
      range of clinical scenarios. 95% of all respondents identified that professional
      or regulatory body guidelines are an important resource when considering handling
      practices. CONCLUSION: Monoclonal antibodies are most commonly handled according
      to cytotoxic drug standards and often in the absence of formal guidelines.

PMID- 25398312
TI  - Pattern recognition as a concept for multiple-choice questions in a national
      licensing exam.
AB  - BACKGROUND: Multiple-choice questions (MCQ) are still widely used in high stakes
      medical exams. We wanted to examine whether and to what extent a national
      licensing exam uses the concept of pattern recognition to test applied clinical
      knowledge. METHODS: We categorized all 4,134 German National medical licensing
      exam questions between October 2006 and October 2012 by discipline, year, and
      type. We analyzed questions from the four largest disciplines: internal medicine
      (n = 931), neurology (n = 305), pediatrics (n = 281), and surgery (n = 233), with
      respect to the following question types: knowledge questions (KQ), pattern
      recognition questions (PRQ), inverse PRQ (IPRQ), and pseudo PRQ (PPRQ). RESULTS:
      A total 51.1% of all questions were of a higher taxonomical order (PRQ and IPRQ)
      with a significant decrease in the percentage of these questions (p <0.001) from
      2006 (61.5%) to 2012 (41.6%). The proportion of PRQs and IPRQs was significantly
      lower (p <0.001) in internal medicine and surgery, compared to neurology and
      pediatrics. PRQs were mostly used in questions about diagnoses (71.7%). A
      significantly higher (p <0.05) percentage of PR/therapy questions was found for
      internal medicine compared with neurology and pediatrics. CONCLUSION: The concept
      of pattern recognition is used with different priorities and to various extents
      by the different disciplines in a high stakes exam to test applied clinical
      knowledge. Being aware of this concept may aid in the design and balance of MCQs
      in an exam with respect to testing clinical reasoning as a desired skill at the
      threshold of postgraduate medical education.

PMID- 25398313
TI  - Phenomapping for novel classification of heart failure with preserved ejection
      fraction.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a
      heterogeneous clinical syndrome in need of improved phenotypic classification. We
      sought to evaluate whether unbiased clustering analysis using dense phenotypic
      data (phenomapping) could identify phenotypically distinct HFpEF categories.
      METHODS AND RESULTS: We prospectively studied 397 patients with HFpEF and
      performed detailed clinical, laboratory, ECG, and echocardiographic phenotyping
      of the study participants. We used several statistical learning algorithms,
      including unbiased hierarchical cluster analysis of phenotypic data (67
      continuous variables) and penalized model-based clustering, to define and
      characterize mutually exclusive groups making up a novel classification of HFpEF.
      All phenomapping analyses were performed by investigators blinded to clinical
      outcomes, and Cox regression was used to demonstrate the clinical validity of
      phenomapping. The mean age was 65+/-12 years; 62% were female; 39% were black;
      and comorbidities were common. Although all patients met published criteria for
      the diagnosis of HFpEF, phenomapping analysis classified study participants into
      3 distinct groups that differed markedly in clinical characteristics, cardiac
      structure/function, invasive hemodynamics, and outcomes (eg, phenogroup 3 had an
      increased risk of HF hospitalization [hazard ratio, 4.2; 95% confidence interval,
      2.0-9.1] even after adjustment for traditional risk factors [P<0.001]). The HFpEF
      phenogroup classification, including its ability to stratify risk, was
      successfully replicated in a prospective validation cohort (n=107). CONCLUSIONS:
      Phenomapping results in a novel classification of HFpEF. Statistical learning
      algorithms applied to dense phenotypic data may allow improved classification of
      heterogeneous clinical syndromes, with the ultimate goal of defining
      therapeutically homogeneous patient subclasses.

PMID- 25398314
TI  - New foe treated with old guns - supportive role of steroids in the treatment of
      acute severe hepatitis E.
AB  - BACKGROUND: Autochthonous hepatitis E has been observed with growing incidence in
      industrialized countries. Hepatitis E virus infection causes an acute hepatitis
      with spontaneous resolution in the majority of cases. However, in individual
      cases, hepatitis E may lead to life-threatening acute liver failure. In this
      report, we describe a case of acute liver injury caused by an autochthonous
      hepatitis E that resolved under steroid treatment. To our knowledge, this is the
      first case report describing supportive steroid monotherapy for acute liver
      injury due to hepatitis E. CASE PRESENTATION: A 63-year-old Caucasian male
      presented with acute liver injury of unknown origin. After excluding the most
      prevalent causes of acute liver injury, liver histology revealed signs of immune
      mediated toxic or drug-induced liver injury. Therefore, immunosuppressive
      treatment with prednisolone was started. After initialization of steroid
      treatment, polymerase chain reaction analyses of peripheral blood and liver
      tissue revealed an acute hepatitis E virus infection (genotype 3). Under
      sustained steroid treatment, acute liver injury improved and hepatitis E
      infection resolved. CONCLUSION: Steroid treatment might be an option to prevent
      progress of life-threatening liver failure and liver transplantation in patients
      with hepatitis E-induced acute liver injury and high-grade inflammation.

PMID- 25398315
TI  - Time and dose effects of cigarette smoke and acrolein on protein carbonyl
      formation in HaCaT keratinocytes.
AB  - Cigarette smoke (CS) is an important environmental source of human exposure to a
      highly toxic and chemically active alpha,beta-unsaturated aldehyde: acrolein. It
      is capable of causing protein carbonylation and dysfunction, especially in oral
      tissues of smokers, constantly exposed to CS toxic constituents. The foremost
      damage is considered to be cumulative, but even a short exposure can be
      potentially harmful. The objectives of the current study were to examine the
      short time and dose effects of direct CS and acrolein exposure on intracellular
      protein carbonylation in epithelial cells. HaCaT-keratinocytes were exposed to
      different doses of acrolein and whole phase CS using a unique smoking simulator
      apparatus that mimics the exposure in smokers. The rate of intracellular protein
      carbonyl modification was examined 10-60 min after the exposure by Western blot.
      In addition, the effect of pre-incubation with a thiol scavenger N-acetylcysteine
      (NAC) was also assessed. We found that intracellular protein carbonyls increased
      as fast as 10 min after CS exposure and their concentration doubled after 20 min,
      with a slight elevation afterwards. Also, carbonyl levels increased gradually as
      CS and acrolein doses were elevated. Addition of 1 mM NAC neutralized part of the
      damage. We conclude that CS and acrolein intracellular protein carbonylation is
      dose- and time- dependent. Even a short time exposure to CS and its aldehydic
      constituents can be potentially harmful. 

PMID- 25398316
TI  - Epidemiological and clinical reasons for vaccination against pertussis and
      influenza in pregnant women.
AB  - Vaccinations in pregnancy are an important aspect of prenatal care for improving
      both maternal health and neonatal outcomes. Despite the fact that protection
      against some infectious diseases for pregnant women can be easily provided
      through immunizations, current coverage rates are low. Two vaccines are notably
      recommended during pregnancy: influenza and the combined tetanus, diphtheria and
      acellular pertussis (Tdap) vaccine. In this review the authors discuss current
      recommendations for vaccination against pertussis and influenza in pregnant women
      in terms of epidemiological, clinical, and immunological reasons, taking into
      account safety and effectiveness. Promoting patients' awareness about pertussis
      and influenza and encouraging general practitioners, nurses and obstetricians to
      recommend the pertussis booster and influenza vaccine will hopefully increase the
      number of pregnant women who choose to become vaccinated. 

PMID- 25398318
TI  - Effect of molecular-level insulation on the performance of a dye-sensitized solar
      cell: fluorescence studies in solid state.
AB  - The performance of a dye-sensitized solar cell (DSSC) that is based on the host
      guest encapsulation of 5-[4-diphenylamino)phenyl]thiophene-2-cyanoacrylic acid
      (L1) inside beta-cyclodextrin hosts has been tested. The formation of the complex
      in the solid state and when adsorbed on TiO(2) was characterized using steady and
      picosecond time-resolved emission techniques, as well as time dependent DFT
      calculations. The molecular-level insulation has led to a small enhancement in
      the energy-conversion performance of the fabricated DSSC with the best results
      being an increase in the open circuit voltage (Voc) from 0.7 to 0.8 V. The
      importance of the present investigation lies in the unique spectroscopic
      characterizations of the examined materials in the solid state.

PMID- 25398317
TI  - An increase in integrin-linked kinase non-canonically confers NF-kappaB-mediated
      growth advantages to gastric cancer cells by activating ERK1/2.
AB  - BACKGROUND: Increased activity or expression of integrin-linked kinase (ILK),
      which regulates cell adhesion, migration, and proliferation, leads to
      oncogenesis. We identified the molecular basis for the regulation of ILK and its
      alternative role in conferring ERK1/2/NF-kappaB-mediated growth advantages to
      gastric cancer cells. RESULTS: Inhibiting ILK with short hairpin RNA or T315, a
      putative ILK inhibitor, abolished NF-kappaB-mediated the growth in the human
      gastric cancer cells AGS, SNU-1, MKN45, and GES-1. ILK stimulated Ras activity to
      activate the c-Raf/MEK1/2/ERK1/2/ribosomal S6 kinase/inhibitor of kappaBalpha/NF
      kappaB signaling by facilitating the formation of the IQ motif-containing GTPase
      activating protein 1 (IQGAP1)-Ras complex. Forced enzymatic ILK expression
      promoted cell growth by facilitating ERK1/2/NF-kappaB signaling. PI3K activation
      or decreased PTEN expression prolonged ERK1/2 activation by protecting ILK from
      proteasome-mediated degradation. C-terminus of heat shock cognate 70 interacting
      protein, an HSP90-associated E3 ubiquitin ligase, mediated ILK ubiquitination to
      control PI3K- and HSP90-regulated ILK stabilization and signaling. In addition to
      cell growth, the identified pathway promoted cell migration and reduced the
      sensitivity of gastric cancer cells to the anticancer agents 5-fluorouracil and
      cisplatin. Additionally, exogenous administration of EGF as well as
      overexpression of EGFR triggered ILK- and IQGAP1-regulated ERK1/2/NF-kappaB
      activation, cell growth, and migration. CONCLUSION: An increase in ILK non
      canonically promotes ERK1/2/NF-kappaB activation and leads to the growth of
      gastric cancer cells.

PMID- 25398319
TI  - MedCHAMPS: Mediterranean studies of cardiovascular disease and hyperglycaemia:
      analytical modelling of population socio-economic transitions.

PMID- 25398320
TI  - Enduring inequality: educational disparities in health among the oldest old in
      Sweden 1992-2011.
AB  - OBJECTIVES: Although the past two decades have involved changes in the living
      conditions of the oldest old in Sweden, little is known about how health
      inequalities have developed in this group during the period. This study explores
      the educational disparities in a wide range of health outcomes among the oldest
      old in Sweden between 1992 and 2011. METHODS: The study uses the repeated cross
      sectional design of the SWEOLD survey, a nationally representative survey of the
      oldest old in Sweden with comparable data from 1992, 2002, and 2011. The
      development of educational disparities in health was tracked across the three
      waves. RESULTS: The results show that although the prevalence of most health
      problems increased during the period, the prevalence of disability in activities
      of daily living decreased. Despite these changes, educational disparities in
      health remained largely unaffected. CONCLUSIONS: The results of the study suggest
      that the association between education and health is remarkably robust. It
      prevailed into the oldest age groups, was consistently found for a wide range of
      health problems, and tended to be stable over extended periods of time.

PMID- 25398322
TI  - Genome sequence and phenotypic characterization of Caulobacter segnis.
AB  - Caulobacter segnis is a unique species of Caulobacter that was initially deemed
      Mycoplana segnis because it was isolated from soil and appeared to share a number
      of features with other Mycoplana. After a 16S rDNA analysis showed that it was
      closely related to Caulobacter crescentus, it was reclassified C. segnis. Because
      the C. segnis genome sequence available in GenBank contained 126 pseudogenes, we
      compared the original sequencing data to the GenBank sequence and determined that
      many of the pseudogenes were due to sequence errors in the GenBank sequence.
      Consequently, we used multiple approaches to correct and reannotate the C. segnis
      genome sequence. In total, we deleted 247 bp, added 14 bp, and changed 8 bp
      resulting in 233 fewer bases in our corrected sequence. The corrected sequence
      contains only 15 pseudogenes compared to 126 in the original annotation.
      Furthermore, we found that unlike Mycoplana, C. segnis divides by fission,
      producing swarmer cells that have a single, polar flagellum.

PMID- 25398321
TI  - Increase of angiotensin II type 1 receptor auto-antibodies in Huntington's
      disease.
AB  - BACKGROUND: In the recent years, a role of the immune system in Huntington's
      disease (HD) is increasingly recognized. Here we investigate the presence of T
      cell activating auto-antibodies against angiotensin II type 1 receptors (AT1R) in
      all stages of the disease as compared to healthy controls and patients suffering
      from multiple sclerosis (MS) as a prototype neurologic autoimmune disease.
      RESULTS: As compared to controls, MS patients show higher titers of anti-AT1R
      antibodies, especially in individuals with active disease. In HD, anti-AT1R
      antibodies are more frequent than in healthy controls or even MS and occur in
      37.9% of patients with relevant titers >= 20 U/ml. In a correlation analysis with
      clinical parameters, the presence of AT1R antibodies in the sera of HD
      individuals inversely correlated with the age of onset and positively with the
      disease burden score as well as with smoking and infection. CONCLUSIONS: These
      data suggest a dysfunction of the adaptive immune system in HD which may be
      triggered by different stimuli including autoimmune responses, infection and
      possibly also smoking.

PMID- 25398323
TI  - Functional role of bdm during flagella biogenesis in Escherichia coli.
AB  - The biofilm-dependent modulation gene (bdm) has recently been shown to play a
      role in osmotic-induced formation of biofilm in Escherichia coli. In this study,
      we demonstrated that deletion of bdm results in down-regulation of flagella
      biosynthesis genes and, consequently, a defect in E. coli motility. In addition,
      we employed atomic force microscopy to confirm the absence of flagella-like
      structures on the surface of bdm-null cells. These findings indicate that bdm
      plays a key role in regulatory pathway for the formation of flagella. 

PMID- 25398325
TI  - Gene targeting RhoA reveals its essential role in coordinating mitochondrial
      function and thymocyte development.
AB  - Thymocyte development is regulated by complex signaling pathways. How these
      signaling cascades are coordinated remains elusive. RhoA of the Rho family small
      GTPases plays an important role in actin cytoskeleton organization, cell
      adhesion, migration, proliferation, and survival. Nonetheless, the physiological
      function of RhoA in thymocyte development is not clear. By characterizing a
      conditional gene targeting mouse model bearing T cell deletion of RhoA, we show
      that RhoA critically regulates thymocyte development by coordinating multiple
      developmental events. RhoA gene disruption caused a strong developmental block at
      the pre-TCR checkpoint and during positive selection. Ablation of RhoA led to
      reduced DNA synthesis in CD4(-)CD8(-), CD4(+)CD8(-), and CD4(-)CD8(+) thymocytes
      but not in CD4(+)CD8(+) thymocytes. Instead, RhoA-deficient CD4(+)CD8(+)
      thymocytes showed an impaired mitosis. Furthermore, we found that abrogation of
      RhoA led to an increased apoptosis in all thymocyte subpopulations. Importantly,
      we show that the increased apoptosis was resulted from reduced pre-TCR expression
      and increased production of reactive oxygen species (ROS), which may be because
      of an enhanced mitochondrial function, as manifested by increased oxidative
      phosphorylation, glycolysis, mitochondrial membrane potential, and mitochondrial
      biogenesis in RhoA-deficient thymocytes. Restoration of pre-TCR expression or
      treatment of RhoA-deficient mice with a ROS scavenger N-acetylcysteine partially
      restored thymocyte development. These results suggest that RhoA is required for
      thymocyte development and indicate, to our knowledge, for the first time that
      fine-tuning of ROS production by RhoA, through a delicate control of metabolic
      circuit, may contribute to thymopoiesis. 

PMID- 25398324
TI  - Antibody to the gp120 V1/V2 loops and CD4+ and CD8+ T cell responses in
      protection from SIVmac251 vaginal acquisition and persistent viremia.
AB  - The human papillomavirus pseudovirions (HPV-PsVs) approach is an effective gene
      delivery system that can prime or boost an immune response in the vaginal tract
      of nonhuman primates and mice. Intravaginal vaccination with HPV-PsVs expressing
      SIV genes, combined with an i.m. gp120 protein injection, induced humoral and
      cellular SIV-specific responses in macaques. Priming systemic immune responses
      with i.m. immunization with ALVAC-SIV vaccines, followed by intravaginal HPV-PsV
      SIV/gp120 boosting, expanded and/or recruited T cells in the female genital
      tract. Using a stringent repeated low-dose intravaginal challenge with the highly
      pathogenic SIVmac251, we show that although these regimens did not demonstrate
      significant protection from virus acquisition, they provided control of viremia
      in a number of animals. High-avidity Ab responses to the envelope gp120 V1/V2
      region correlated with delayed SIVmac251 acquisition, whereas virus levels in
      mucosal tissues were inversely correlated with antienvelope CD4(+) T cell
      responses. CD8(+) T cell depletion in animals with controlled viremia caused an
      increase in tissue virus load in some animals, suggesting a role for CD8(+) T
      cells in virus control. This study highlights the importance of CD8(+) cells and
      antienvelope CD4(+) T cells in curtailing virus replication and antienvelope
      V1/V2 Abs in preventing SIVmac251 acquisition. 

PMID- 25398327
TI  - Lipocalin 2 imparts selective pressure on bacterial growth in the bladder and is
      elevated in women with urinary tract infection.
AB  - Competition for iron is a critical component of successful bacterial infections,
      but the underlying in vivo mechanisms are poorly understood. We have previously
      demonstrated that lipocalin 2 (LCN2) is an innate immunity protein that binds to
      bacterial siderophores and starves them for iron, thus representing a novel host
      defense mechanism to infection. In the present study we show that LCN2 is
      secreted by the urinary tract mucosa and protects against urinary tract infection
      (UTI). We found that LCN2 was expressed in the bladder, ureters, and kidneys of
      mice subject to UTI. LCN2 was protective with higher bacterial numbers retrieved
      from bladders of Lcn2-deficient mice than from wild-type mice infected with the
      LCN2-sensitive Escherichia coli strain H9049. Uropathogenic E. coli mutants in
      siderophore receptors for salmochelin, aerobactin, or yersiniabactin displayed
      reduced fitness in wild-type mice, but not in mice deficient of LCN2,
      demonstrating that LCN2 imparts a selective pressure on bacterial growth in the
      bladder. In a human cohort of women with recurrent E. coli UTIs, urine LCN2
      levels were associated with UTI episodes and with levels of bacteriuria. The
      number of siderophore systems was associated with increasing bacteriuria during
      cystitis. Our data demonstrate that LCN2 is secreted by the urinary tract mucosa
      in response to uropathogenic E. coli challenge and acts in innate immune defenses
      as a colonization barrier that pathogens must overcome to establish infection. 

PMID- 25398326
TI  - Definition of the cattle killer cell Ig-like receptor gene family: comparison
      with aurochs and human counterparts.
AB  - Under selection pressure from pathogens, variable NK cell receptors that
      recognize polymorphic MHC class I evolved convergently in different species of
      placental mammal. Unexpectedly, diversified killer cell Ig-like receptors (KIRs)
      are shared by simian primates, including humans, and cattle, but not by other
      species. Whereas much is known of human KIR genetics and genomics, knowledge of
      cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the
      cattle and human KIR gene families, we determined the genomic location,
      structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of
      aurochs, the extinct wild ancestor of domestic cattle. Larger than its human
      counterpart, the cattle KIR locus evolved through successive duplications of a
      block containing ancestral KIR3DL and KIR3DX genes that existed before placental
      mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are
      polymorphic and the gene organization and content appear conserved. Of 18 genes,
      8 are functional and 10 were inactivated by point mutation. Selective
      inactivation of KIR3DL and activating receptor genes leaves a functional cohort
      of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX.
      Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian
      primates. Although independently evolved, cattle and human KIR gene families
      share important function-related properties, indicating that cattle KIR are NK
      cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are
      the major genetic factors associated with human disease and merit investigation
      in cattle. 

PMID- 25398328
TI  - CCAAT/enhancer-binding protein alpha negatively regulates IFN-gamma expression in
      T cells.
AB  - Humoral immunity, including Ab switching and somatic hypermutation, is critically
      regulated by CD4(+) T cells. T follicular helper (Tfh) cells have been recently
      shown to be a distinct T cell subset important in germinal center reactions. The
      transcriptional regulation of Tfh cell development and function has not been well
      understood. In this study, we report that C/EBPalpha, a basic region/leucine
      zipper transcription factor, is highly expressed in Tfh cells. Cebpa-deficient
      CD4(+) T cells exhibit enhanced IFN-gamma expression in vitro and in vivo. T cell
      specific Cebpa knockout mice, although not defective in Tfh cell generation,
      produce significantly increased levels of IgG2a/b and IgG3 following immunization
      with a protein Ag. Moreover, C/EBPalpha binds to the Ifng gene and inhibits T-bet
      driven Ifng transcription in a DNA binding-dependent manner. Our study thus
      demonstrates that C/EBPalpha restricts IFN-gamma expression in T cells to allow
      proper class switching by B cells. 

PMID- 25398331
TI  - Hemodynamics in the microcirculation and in microfluidics.
AB  - Hemodynamics in microcirculation is important for hemorheology and several types
      of circulatory disease. Although hemodynamics research has a long history, the
      field continues to expand due to recent advancements in numerical and
      experimental techniques at the micro-and nano-scales. In this paper, we review
      recent computational and experimental studies of blood flow in microcirculation
      and microfluidics. We first focus on the computational studies of red blood cell
      (RBC) dynamics, from the single cellular level to mesoscopic multiple cellular
      flows, followed by a review of recent computational adhesion models for white
      blood cells, platelets, and malaria-infected RBCs, in which the cell adhesion to
      the vascular wall is essential for cellular function. Recent developments in
      optical microscopy have enabled the observation of flowing blood cells in
      microfluidics. Experimental particle image velocimetry and particle tracking
      velocimetry techniques are described in this article. Advancements in micro total
      analysis system technologies have facilitated flowing cell separation with
      microfluidic devices, which can be used for biomedical applications, such as a
      diagnostic tool for breast cancer or large intestinal tumors. In this paper, cell
      separation techniques are reviewed for microfluidic devices, emphasizing recent
      advances and the potential of this fast-evolving research field in the near
      future. 

PMID- 25398332
TI  - Three-Dimensional Blood Vessel Segmentation and Centerline Extraction based on
      Two-Dimensional Cross-Section Analysis.
AB  - The segmentation of tubular tree structures like vessel systems in volumetric
      datasets is of vital interest for many medical applications. In this paper we
      present a novel, semi-automatic method for blood vessel segmentation and
      centerline extraction, by tracking the blood vessel tree from a user-initiated
      seed point to the ends of the blood vessel tree. The novelty of our method is in
      performing only two-dimensional cross-section analysis for segmentation of the
      connected blood vessels. The cross-section analysis is done by our novel single
      scale or multi-scale circle enhancement filter, used at the blood vessel trunk or
      bifurcation, respectively. The method was validated for both synthetic and
      medical images. Our validation has shown that the cross-sectional centerline
      error for our method is below 0.8 pixels and the Dice coefficient for our
      segmentation is 80% +/- 2.7%. On combining our method with an optional active
      contour post-processing, the Dice coefficient for the resulting segmentation is
      found to be 94% +/- 2.4%. Furthermore, by restricting the image analysis to the
      regions of interest and converting most of the three-dimensional calculations to
      two-dimensional calculations, the processing was found to be more than 18 times
      faster than Frangi vesselness with thinning, 8 times faster than user-initiated
      active contour segmentation with thinning and 7 times faster than our previous
      method. 

PMID- 25398329
TI  - Stimulation of Superficial Zone Protein/Lubricin/PRG4 by Transforming Growth
      Factor-beta in Superficial Zone Articular Chondrocytes and Modulation by
      Glycosaminoglycans.
AB  - Superficial zone protein (SZP), also known as lubricin and proteoglycan 4 (PRG4),
      plays an important role in the boundary lubrication of articular cartilage and is
      regulated by transforming growth factor (TGF)-beta. Here, we evaluate the role of
      cell surface glycosaminoglycans (GAGs) during TGF-beta1 stimulation of
      SZP/lubricin/PRG4 in superficial zone articular chondrocytes. We utilized primary
      monolayer superficial zone articular chondrocyte cultures and treated them with
      various concentrations of TGF-beta1, in the presence or absence of heparan
      sulfate (HS), heparin, and chondroitin sulfate (CS). The cell surface GAGs were
      removed by pretreatment with either heparinase I or chondroitinase-ABC before TGF
      beta1 stimulation. Accumulation of SZP/lubricin/PRG4 in the culture medium in
      response to stimulation with TGF-beta1 and various exogenous GAGs was
      demonstrated by immunoblotting and quantitated by enzyme-linked immunosorbent
      assay. We show that TGF-beta1 and exogenous HS enhanced SZP accumulation of
      superficial zone chondrocytes in the presence of surface GAGs. At the dose of 1
      ng/mL of TGF-beta1, the presence of exogenous heparin inhibited SZP accumulation
      whereas the presence of exogenous CS stimulated SZP accumulation in the culture
      medium. Enzymatic depletion of GAGs on the surface of superficial zone
      chondrocytes enhanced the ability of TGF-beta1 to stimulate SZP accumulation in
      the presence of both exogenous heparin and CS. Collectively, these results
      suggest that GAGs at the surface of superficial zone articular chondrocytes
      influence the response to TGF-beta1 and exogenous GAGs to stimulate SZP
      accumulation. Cell surface GAGs modulate superficial zone chondrocytes' response
      to TGF-beta1 and exogenous HS.

PMID- 25398333
TI  - In vitro enzymology of Cas9.
AB  - Cas9 is a bacterial RNA-guided endonuclease that uses base pairing to recognize
      and cleave target DNAs with complementarity to the guide RNA. The programmable
      sequence specificity of Cas9 has been harnessed for genome editing and gene
      expression control in many organisms. Here, we describe protocols for the
      heterologous expression and purification of recombinant Cas9 protein and for in
      vitro transcription of guide RNAs. We describe in vitro reconstitution of the
      Cas9-guide RNA ribonucleoprotein complex and its use in endonuclease activity
      assays. The methods outlined here enable mechanistic characterization of the RNA
      guided DNA cleavage activity of Cas9 and may assist in further development of the
      enzyme for genetic engineering applications. 

PMID- 25398334
TI  - Targeted genome editing in human cells using CRISPR/Cas nucleases and truncated
      guide RNAs.
AB  - CRISPR RNA-guided nucleases have recently emerged as a robust genome-editing
      platform that functions in a wide range of organisms. To reduce off-target
      effects of these nucleases, we developed and validated a modified system that
      uses truncated guide RNAs (tru-gRNAs). The use of tru-gRNAs leads to decreases in
      off-target effects and does not generally compromise the on-target efficiencies
      of these genome-editing nucleases. In this chapter, we describe guidelines for
      identifying potential tru-gRNA target sites and protocols for measuring the on
      target efficiencies of CRISPR RNA-guided nucleases in human cells. 

PMID- 25398336
TI  - Genome engineering with custom recombinases.
AB  - Site-specific recombinases are valuable tools for myriad basic research and
      genome engineering applications. In particular, hybrid recombinases consisting of
      catalytic domains from the resolvase/invertase family of serine recombinases
      fused to Cys2-His2 zinc-finger or TAL effector DNA-binding domains are capable of
      introducing targeted modifications into mammalian cells. Due to their inherent
      modularity, new recombinases with distinct targeting specificities can readily be
      generated and utilized in a "plug-and-play" manner. In this protocol, we provide
      detailed, step-by-step instructions for generating new hybrid recombinases with
      user-defined specificity, as well as methods for achieving site-specific
      integration into targeted genomic loci using these systems. 

PMID- 25398335
TI  - Determining the specificities of TALENs, Cas9, and other genome-editing enzymes.
AB  - The rapid development of programmable site-specific endonucleases has led to a
      dramatic increase in genome engineering activities for research and therapeutic
      purposes. Specific loci of interest in the genomes of a wide range of organisms
      including mammals can now be modified using zinc-finger nucleases, transcription
      activator-like effectornucleases, and CRISPR-associated Cas9 endonucleases in a
      site-specific manner, in some cases requiring relatively modest effort for
      endonuclease design, construction, and application. While these technologies have
      made genome engineering widely accessible, the ability of programmable nucleases
      to cleave off-target sequences can limit their applicability and raise concerns
      about therapeutic safety. In this chapter, we review methods to evaluate and
      improve the DNA cleavage activity of programmable site-specific endonucleases and
      describe a procedure for a comprehensive off-target profiling method based on the
      in vitro selection of very large (~10(12)-membered) libraries of potential
      nuclease substrates. 

PMID- 25398337
TI  - Genome engineering in human cells.
AB  - Genome editing in human cells is of great value in research, medicine, and
      biotechnology. Programmable nucleases including zinc-finger nucleases,
      transcription activator-like effector nucleases, and RNA-guided engineered
      nucleases recognize a specific target sequence and make a double-strand break at
      that site, which can result in gene disruption, gene insertion, gene correction,
      or chromosomal rearrangements. The target sequence complexities of these
      programmable nucleases are higher than 3.2 mega base pairs, the size of the
      haploid human genome. Here, we briefly introduce the structure of the human
      genome and the characteristics of each programmable nuclease, and review their
      applications in human cells including pluripotent stem cells. In addition, we
      discuss various delivery methods for nucleases, programmable nickases, and
      enrichment of gene-edited human cells, all of which facilitate efficient and
      precise genome editing in human cells. 

PMID- 25398338
TI  - Genome editing in human stem cells.
AB  - The use of custom-engineered sequence-specific nucleases (including CRISPR/Cas9,
      ZFN, and TALEN) allows genetic changes in human cells to be easily made with much
      greater efficiency and precision than before. Engineered double-stranded DNA
      breaks can efficiently disrupt genes, or, with the right donor vector, engineer
      point mutations and gene insertions. However, a number of design considerations
      should be taken into account to ensure maximum gene targeting efficiency and
      specificity. This is especially true when engineering human embryonic stem or
      induced pluripotent stem cells (iPSCs), which are more difficult to transfect and
      less resilient to DNA damage than immortalized tumor cell lines. Here, we
      describe a protocol for easily engineering genetic changes in human iPSCs,
      through which we typically achieve targeting efficiencies between 1% and 10%
      without any subsequent selection steps. Since this protocol only uses the simple
      transient transfection of plasmids and/or single-stranded oligonucleotides, most
      labs will easily be able to perform it. We also describe strategies for
      identifying, cloning, and genotyping successfully edited cells, and how to design
      the optimal sgRNA target sites and donor vectors. Finally, we discuss alternative
      methods for gene editing including viral delivery vectors, Cas9 nickases, and
      orthogonal Cas9 systems. 

PMID- 25398339
TI  - Tagging endogenous loci for live-cell fluorescence imaging and molecule counting
      using ZFNs, TALENs, and Cas9.
AB  - The programmable ZFN, TALEN, and Cas9 nucleases allow genome editing of any cell
      line or organism. In this chapter, we describe methods to create gene fusions at
      endogenous loci in mammalian cells to express fluorescent fusions of proteins of
      interest at endogenous levels. The donor DNA, which includes the sequence
      encoding a fluorescent protein, is provided to the cell to repair a double-strand
      break induced by a nuclease. The engineered donor sequence is integrated by
      homology-directed repair into the genome in frame with the coding region of the
      gene of interest, resulting in expression of a fusion protein at physiological
      levels. We further describe techniques to study protein dynamics and numbers
      using the genome-edited cell lines. In contrast to cell lines stably
      overexpressing fusion proteins from modified cDNAs, genes encoding fluorescent
      proteins are targeted to the endogenous genetic locus, avoiding perturbation of
      alternative splicing and expression levels. 

PMID- 25398340
TI  - Genome editing using Cas9 nickases.
AB  - The RNA-guided, sequence-specific endonuclease Cas9 has been widely adopted as
      genome engineering tool due to its efficiency and ease of use. Derived from the
      microbial CRISPR (clustered regularly interspaced short palindromic repeat) type
      II adaptive immune system, Cas9 has now been successfully engineered for genome
      editing applications in a variety of animal and plant species. To reduce
      potential off-target mutagenesis by wild-type Cas9, homology- and structure
      guided mutagenesis of Streptococcus pyogenes Cas9 catalytic domains has produced
      "nicking" enzymes (Cas9n) capable of inducing single-strand nicks rather than
      double-strand breaks. Since nicks are generally repaired with high fidelity in
      eukaryotic cells, Cas9n can be leveraged to mediate highly specific genome
      editing, either via nonhomologous end-joining or homology-directed repair. Here
      we describe the preparation, testing, and application of Cas9n reagents for
      precision mammalian genome engineering. 

PMID- 25398341
TI  - Assaying break and nick-induced homologous recombination in mammalian cells using
      the DR-GFP reporter and Cas9 nucleases.
AB  - Thousands of DNA breaks occur daily in mammalian cells, including potentially
      tumorigenic double-strand breaks (DSBs) and less dangerous but vastly more
      abundant single-strand breaks (SSBs). The majority of SSBs are quickly repaired,
      but some can be converted to DSBs, posing a threat to the integrity of the
      genome. Although SSBs are usually repaired by dedicated pathways, they can also
      trigger homologous recombination (HR), an error-free pathway generally associated
      with DSB repair. While HR-mediated DSB repair has been extensively studied, the
      mechanisms of HR-mediated SSB repair are less clear. This chapter describes a
      protocol to investigate SSB-induced HR in mammalian cells employing the DR-GFP
      reporter, which has been widely used in DSB repair studies, together with an
      adapted bacterial CRISPR/Cas system. 

PMID- 25398342
TI  - Adapting CRISPR/Cas9 for functional genomics screens.
AB  - The use of CRISPR/Cas9 (clustered regularly interspaced short palindromic
      repeats/CRISPR-associated protein) for targeted genome editing has been widely
      adopted and is considered a "game changing" technology. The ease and rapidity by
      which this approach can be used to modify endogenous loci in a wide spectrum of
      cell types and organisms makes it a powerful tool for customizable genetic
      modifications as well as for large-scale functional genomics. The development of
      retrovirus-based expression platforms to simultaneously deliver the Cas9 nuclease
      and single guide (sg) RNAs provides unique opportunities by which to ensure
      stable and reproducible expression of the editing tools and a broad cell
      targeting spectrum, while remaining compatible with in vivo genetic screens.
      Here, we describe methods and highlight considerations for designing and
      generating sgRNA libraries in all-in-one retroviral vectors for such
      applications. 

PMID- 25398343
TI  - The iCRISPR platform for rapid genome editing in human pluripotent stem cells.
AB  - Human pluripotent stem cells (hPSCs) have the potential to generate all adult
      cell types, including rare or inaccessible human cell populations, thus providing
      a unique platform for disease studies. To realize this promise, it is essential
      to develop methods for efficient genetic manipulations in hPSCs. Established
      using TALEN (transcription activator-like effector nuclease) and CRISPR
      (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR
      associated) systems, the iCRISPR platform supports a variety of genome
      engineering approaches with high efficiencies. Here, we first describe the
      establishment of the iCRISPR platform through TALEN-mediated targeting of
      inducible Cas9 expression cassettes into the AAVS1 locus. Next, we provide a
      series of technical procedures for using iCRISPR to achieve one-step knockout of
      one or multiple gene(s), "scarless" introduction of precise nucleotide
      alterations, as well as inducible knockout during hPSC differentiation. We
      present an optimized workflow, as well as guidelines for the selection of CRISPR
      targeting sequences and the design of single-stranded DNA (ssDNA) homology
      directed DNA repair templates for the introduction of specific nucleotide
      alterations. We have successfully used these protocols in four different hPSC
      lines, including human embryonic stem cells and induced pluripotent stem cells.
      Once the iCRISPR platform is established, clonal lines with desired genetic
      modifications can be established in as little as 1 month. The methods described
      here enable a wide range of genome-engineering applications in hPSCs, thus
      providing a valuable resource for the creation of diverse hPSC-based disease
      models with superior speed and ease. 

PMID- 25398344
TI  - Creating cancer translocations in human cells using Cas9 DSBs and nCas9 paired
      nicks.
AB  - Recurrent chromosomal translocations are found in numerous tumor types, often
      leading to the formation and expression of fusion genes with oncogenic potential.
      Creating chromosomal translocations at the relevant endogenous loci, rather than
      ectopically expressing the fusion genes, opens new possibilities for better
      characterizing molecular mechanisms driving tumor formation. In this chapter, we
      describe methods to create cancer translocations in human cells. DSBs or paired
      nicks generated by either wild-type Cas9 or the Cas9 nickase, respectively, are
      used to induce translocations at the relevant loci. Using different PCR-based
      methods, we also explain how to quantify translocation frequency and to analyze
      breakpoint junctions in the cells of interest. In addition, PCR detection of
      translocations is used as a very sensitive method to detect off-target effects,
      which has general utility. 

PMID- 25398345
TI  - Genome editing for human gene therapy.
AB  - The rapid advancement of genome-editing techniques holds much promise for the
      field of human gene therapy. From bacteria to model organisms and human cells,
      genome editing tools such as zinc-finger nucleases (ZNFs), TALENs, and
      CRISPR/Cas9 have been successfully used to manipulate the respective genomes with
      unprecedented precision. With regard to human gene therapy, it is of great
      interest to test the feasibility of genome editing in primary human hematopoietic
      cells that could potentially be used to treat a variety of human genetic
      disorders such as hemoglobinopathies, primary immunodeficiencies, and cancer. In
      this chapter, we explore the use of the CRISPR/Cas9 system for the efficient
      ablation of genes in two clinically relevant primary human cell types, CD4+ T
      cells and CD34+ hematopoietic stem and progenitor cells. By using two guide RNAs
      directed at a single locus, we achieve highly efficient and predictable deletions
      that ablate gene function. The use of a Cas9-2A-GFP fusion protein allows FACS
      based enrichment of the transfected cells. The ease of designing, constructing,
      and testing guide RNAs makes this dual guide strategy an attractive approach for
      the efficient deletion of clinically relevant genes in primary human
      hematopoietic stem and effector cells and enables the use of CRISPR/Cas9 for gene
      therapy. 

PMID- 25398346
TI  - Generation of site-specific mutations in the rat genome via CRISPR/Cas9.
AB  - The laboratory rat is a valuable model organism for basic biological studies and
      drug development. However, due to the lack of genetic tools for site-specific
      genetic modification in the rat genome, more and more researchers chose the mouse
      as their favored mammalian models due to the sophisticated embryonic stem cell
      based gene-targeting techniques available. Recently, engineered nucleases,
      including zinc finger nucleases, transcription activator-like effector nucleases,
      and CRISPR/Cas9 systems, have been adapted to generate knockout rats efficiently.
      The purpose of this section is to provide detailed procedures for the generation
      of site-specific mutations in the rat genome through injection of Cas9/sgRNA into
      one-cell embryos. 

PMID- 25398347
TI  - CRISPR/Cas9-based genome editing in mice by single plasmid injection.
AB  - CRISPR/Cas-mediated genome modification has opened a new era for elucidating gene
      function. Gene knockout mice can be generated by injecting humanized Cas9 (hCas9)
      mRNA and guide RNA (sgRNA) into fertilized eggs. However, delivery of RNA instead
      of DNA to the fertilized oocyte requires extra preparation and extra care with
      storage. To simplify the method of delivery, we injected the circular pX330
      plasmids expressing both hCas9 and sgRNA and found that mutant mice were
      generated as efficiently as with RNA injection. Different from the linearized
      plasmid, the circular plasmid decreased the chance of integration into the host
      genome. We also developed the pCAG-EGxxFP reporter plasmid for evaluating the
      sgRNA activity by observing EGFP fluorescence in HEK293T cells. The combination
      of these techniques allowed us to develop a rapid, easy, and reproducible
      strategy for targeted mutagenesis in living mice. This chapter provides an
      experimental protocol for the design of sgRNAs, the construction of pX330-sgRNA
      and pCAG-EGxxFP-target plasmids, the validation of cleavage efficiency in vitro,
      and the generation of targeted gene mutant mice. These mice can be generated
      within a month.

PMID- 25398348
TI  - Imaging genomic elements in living cells using CRISPR/Cas9.
AB  - In addition to their applications in genome editing and gene expression
      regulation, programmable DNA recognition systems, including both CRISPR and TALE,
      have been recently engineered for the visualization of endogenous genomic
      elements in living cells. This capability greatly helps the study of genome
      function regulation by its physical organization and interaction with other
      nuclear structures. This chapter first discusses the general considerations in
      designing and implementing the imaging system. The subsequent sections provide
      detailed protocols to use the CRISPR/Cas9 system to label and image specific
      genomic loci, including the establishment of expression systems for dCas9-GFP and
      sgRNA, the procedure to label repetitive sequences of telomeres and protein
      coding genes, the simultaneous expression of many sgRNAs to label a nonrepetitive
      locus, and the verification of signal specificity by FISH. 

PMID- 25398350
TI  - Cas9-based genome editing in zebrafish.
AB  - Genome editing using the Cas9 endonuclease of Streptococcus pyogenes has
      demonstrated unprecedented efficacy and facility in a wide variety of biological
      systems. In zebrafish, specifically, studies have shown that Cas9 can be directed
      to user-defined genomic target sites via synthetic guide RNAs, enabling random or
      homology-directed sequence alterations, long-range chromosomal deletions,
      simultaneous disruption of multiple genes, and targeted integration of several
      kilobases of DNA. Altogether, these methods are opening new doors for the
      engineering of knock-outs, conditional alleles, tagged proteins, reporter lines,
      and disease models. In addition, the ease and high efficiency of generating Cas9
      mediated gene knock-outs provides great promise for high-throughput functional
      genomics studies in zebrafish. In this chapter, we briefly review the origin of
      CRISPR/Cas technology and discuss current Cas9-based genome-editing applications
      in zebrafish with particular emphasis on their designs and implementations. 

PMID- 25398349
TI  - Cas9-based genome editing in Xenopus tropicalis.
AB  - Xenopus tropicalis has been developed as a model organism for developmental
      biology, providing a system offering both modern genetics and classical
      embryology. Recently, the Clustered Regularly Interspaced Short Palindromic
      Repeats/CRISPR-associated (CRISPR/Cas) system for genome modification has
      provided an additional tool for Xenopus researchers to achieve simple and
      efficient targeted mutagenesis. Here, we provide insights into experimental
      design and procedures permitting successful application of this technique to
      Xenopus researchers, and offer a general strategy for performing loss-of-function
      assays in F0 and subsequently F1 embryos. 

PMID- 25398351
TI  - Cas9-based genome editing in Drosophila.
AB  - Our ability to modify the Drosophila genome has recently been revolutionized by
      the development of the CRISPR system. The simplicity and high efficiency of this
      system allows its widespread use for many different applications, greatly
      increasing the range of genome modification experiments that can be performed.
      Here, we first discuss some general design principles for genome engineering
      experiments in Drosophila and then present detailed protocols for the production
      of CRISPR reagents and screening strategies to detect successful genome
      modification events in both tissue culture cells and animals. 

PMID- 25398352
TI  - Transgene-free genome editing by germline injection of CRISPR/Cas RNA.
AB  - Genome modification by CRISPR/Cas offers its users the ability to target
      endogenous sites in the genome for cleavage and for engineering precise genomic
      changes using template-directed repair, all with unprecedented ease and
      flexibility of targeting. As such, CRISPR/Cas is just part of a set of recently
      developed and rapidly improving tools that offer great potential for researchers
      to functionally access the genomes of organisms that have not previously been
      extensively used in a laboratory setting. We describe in detail protocols for
      using CRISPR/Cas to target genes of experimental organisms, in a manner that does
      not require transformation to obtain transgenic lines and that should be readily
      applicable to a wide range of previously little-studied species. 

PMID- 25398353
TI  - Cas9-based genome editing in Arabidopsis and tobacco.
AB  - Targeted modification of plant genome is key to elucidating and manipulating gene
      functions in plant research and biotechnology. The clustered regularly
      interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)
      technology is emerging as a powerful genome-editing method in diverse plants that
      traditionally lacked facile and versatile tools for targeted genetic engineering.
      This technology utilizes easily reprogrammable guide RNAs (sgRNAs) to direct
      Streptococcus pyogenes Cas9 endonuclease to generate DNA double-stranded breaks
      in targeted genome sequences, which facilitates efficient mutagenesis by error
      prone nonhomologous end-joining (NHEJ) or sequence replacement by homology
      directed repair (HDR). In this chapter, we describe the procedure to design and
      evaluate dual sgRNAs for plant codon-optimized Cas9-mediated genome editing using
      mesophyll protoplasts as model cell systems in Arabidopsis thaliana and Nicotiana
      benthamiana. We also discuss future directions in sgRNA/Cas9 applications for
      generating targeted genome modifications and gene regulations in plants. 

PMID- 25398354
TI  - Multiplex engineering of industrial yeast genomes using CRISPRm.
AB  - Global demand has driven the use of industrial strains of the yeast Saccharomyces
      cerevisiae for large-scale production of biofuels and renewable chemicals.
      However, the genetic basis of desired domestication traits is poorly understood
      because robust genetic tools do not exist for industrial hosts. We present an
      efficient, marker-free, high-throughput, and multiplexed genome editing platform
      for industrial strains of S. cerevisiae that uses plasmid-based expression of the
      CRISPR/Cas9 endonuclease and multiple ribozyme-protected single guide RNAs. With
      this multiplex CRISPR (CRISPRm) system, it is possible to integrate DNA libraries
      into the chromosome for evolution experiments, and to engineer multiple loci
      simultaneously. The CRISPRm tools should therefore find use in many higher-order
      synthetic biology applications to accelerate improvements in industrial
      microorganisms. 

PMID- 25398355
TI  - Protein engineering of Cas9 for enhanced function.
AB  - CRISPR/Cas systems act to protect the cell from invading nucleic acids in many
      bacteria and archaea. The bacterial immune protein Cas9 is a component of one of
      these CRISPR/Cas systems and has recently been adapted as a tool for genome
      editing. Cas9 is easily targeted to bind and cleave a DNA sequence via a
      complementary RNA; this straightforward programmability has gained Cas9 rapid
      acceptance in the field of genetic engineering. While this technology has
      developed quickly, a number of challenges regarding Cas9 specificity, efficiency,
      fusion protein function, and spatiotemporal control within the cell remain. In
      this work, we develop a platform for constructing novel proteins to address these
      open questions. We demonstrate methods to either screen or select active Cas9
      mutants and use the screening technique to isolate functional Cas9 variants with
      a heterologous PDZ domain inserted within the protein. As a proof of concept,
      these methods lay the groundwork for the future construction of diverse Cas9
      proteins. Straightforward and accessible techniques for genetic editing are
      helping to elucidate biology in new and exciting ways; a platform to engineer new
      functionalities into Cas9 will help forge the next generation of genome-modifying
      tools. 

PMID- 25398356
TI  - Methods in Enzymology. The use of CRISPR/Cas9, ZFNs, and TALENs in generating
      site-specific genome alterations. Preface.

PMID- 25398357
TI  - The effect of orthographic form-cuing on the phonological preparation unit in
      spoken word production.
AB  - Two experiments using the form-preparation paradigm were conducted to investigate
      the effect of orthographic form-cuing on the phonological preparation unit during
      spoken word production with native Mandarin speakers. In both experiments,
      participants were instructed to memorize nine prompt-response monosyllabic word
      pairs, after which an associative naming session was conducted in which the
      prompts were presented and participants were asked to say the corresponding
      response names as quickly and accurately as possible. In both experiments, the
      response words in the homogeneous lists shared the same onsets, or shared the
      same rimes; the response names had no common aspects of pronunciation in the
      heterogeneous lists. Chinese characters (Experiment 1) and Pinyin (phonetic
      transcription of the characters) (Experiment 2) were used to investigate the
      effect of the orthographic form. Significant onset facilitation and rime
      inhibition was shown for Pinyin syllables but not for characters. The contrasts
      of the onset and rime effect in the two orthographic forms suggest that a
      specific phonological unit is promoted in spoken word production in a certain
      orthographic form. Pinyin cued the participants to prepare the onset whereas
      Chinese characters did not. The rime interference effect may arise as a result of
      lexical competition in spoken word production. 

PMID- 25398358
TI  - Intra-arterial transplantation of low-dose stem cells provides functional
      recovery without adverse effects after stroke.
AB  - Cell transplantation therapy for cerebral infarction has emerged as a promising
      treatment to reduce brain damage and enhance functional recovery. We previously
      reported that intra-arterial delivery of bone marrow mesenchymal stem cells
      (MSCs) enables superselective cell administration to the infarct area and results
      in significant functional recovery after ischemic stroke in a rat model. However,
      to reduce the risk of embolism caused by the transplanted cells, an optimal cell
      number should be determined. At 24 h after middle cerebral artery occlusion and
      reperfusion, we administered human MSCs (low dose: 1 * 10(4) cells; high dose: 1
      * 10(6) cells) and then assessed functional recovery, inflammatory responses,
      cell distribution, and mortality. Rats treated with high- or low-dose MSCs showed
      behavioral recovery. At day 8 post-stroke, microglial activation was suppressed
      significantly, and interleukin (IL)-1beta and IL-12p70 were reduced in both
      groups. Although high-dose MSCs were more widely distributed in the cortex and
      striatum of rats, the degree of intravascular cell aggregation and mortality was
      significantly higher in the high-dose group. In conclusion, selective intra
      arterial transplantation of low-dose MSCs has anti-inflammatory effects and
      reduces the adverse effects of embolic complication, resulting in sufficient
      functional recovery of the affected brain. 

PMID- 25398359
TI  - Dietary experiences and support needs of women who gain weight following
      chemotherapy for breast cancer.
AB  - PURPOSE: Weight gain is common but poorly understood in women receiving
      chemotherapy for breast cancer. Overweight and obesity are associated with other
      co-morbidities, reduced self-esteem and an increased risk of cancer recurrence.
      The purpose of this study was to explore the experiences, dietary information and
      support needs of women who gain weight during chemotherapy treatment. METHODS:
      This study used a qualitative approach to explore the experiences of women from
      three Melbourne breast cancer clinics. Those who gained weight during the period
      of enrolment in a cohort study of chemotherapy-related taste changes were invited
      to participate in this qualitative interview study. Eligibility for inclusion was
      a gain in body weight between the commencement of chemotherapy and 2 months after
      its completion. Semi-structured interviews explored changes in diet, physical
      activity patterns, weight changes, dietary information and support needs and
      sources. Thematic analysis of the interview data was performed. RESULTS:
      Seventeen women were interviewed. Three key themes emerged from the following
      data: (i) undesirable impacts of cancer treatment on diet and physical activity,
      (ii) surprise and concern associated with changes to weight and diet and (iii)
      insufficient dietary information and support. CONCLUSIONS: This study has
      described the practical and informational dietary support needs of women
      undergoing chemotherapy for breast cancer and reasons for dietary change. There
      may be gaps in information and support provision after diagnosis in the areas of
      weight management, nutrition-related side effects of chemotherapy and healthy
      eating. Models of dietetic practice and the provision of tailored dietary
      information should be explored.

PMID- 25398360
TI  - Prospective surveillance of breast cancer-related lymphoedema in the first-year
      post-surgery: feasibility and comparison of screening measures.
AB  - PURPOSE: To examine the feasibility of a breast cancer-related lymphoedema (BCRL)
      screening programme. Additionally, to investigate the efficacy of bioimpedance
      analysis (BIA) compared to circumferential measurements (CM) in detecting BCRL.
      METHODS: This was a 12-month prospective feasibility study. Participants were
      recruited from two diagnostic breast clinics and consented to be screened for
      BCRL. Pre-surgical assessments were conducted, and participants were followed up
      at quarterly intervals. BIA and CM measurements were conducted at all time
      points. An L-Dex score of >10 or a 10-U increase from baseline or a >=5 %
      increase in proximal, distal or total percentage volume difference (PVD) from
      baseline was indicative of BCRL. Information was collected on subjective
      symptoms, potential risk factors, demographics and medical data. Feasibility was
      based on uptake and retention. RESULTS: One hundred twenty-six participants were
      recruited with an attrition rate of 16.2 %. Participants' mean age was 59 years
      with the majority having stage I (63.9 %), infiltrating ductal carcinoma (87.4
      %). 31.6 % were identified as having BCRL, 90.3 % detected by CM and 35.5 % by
      BIA (p = <=0.0001). We found no significant correlation between BIA and CM.
      Participants identified as having BCRL had a higher BMI, a recent injury to their
      'at-risk' arm and more lymph nodes excised (p = <0.05). These findings were not
      evident across all time points. A large percentage of participants had transient
      BCRL when assessed by a lymphoedema physiotherapist. CONCLUSIONS: BCRL screening
      is acceptable and valued by breast cancer survivors. Work needs to continue to
      establish the most effective screening tool and the natural behaviour of BCRL
      within the first-year post-surgery.

PMID- 25398362
TI  - MR imaging characteristics and clinical symptoms related to displaced meniscal
      flap tears.
AB  - OBJECTIVES: The purpose of our study was (1) to analyze the flap tear location,
      direction of displacement and size on magnetic resonance (MR) imaging, (2) to
      describe associated knee abnormalities including presence of effusion, synovitis,
      bone marrow edema pattern or ligamentous tear, and (3) to assess clinical
      findings found with flap tears, including the pain score, and determine
      differences between operative and nonoperative groups. MATERIALS AND METHODS: A
      retrospective radiology database search over the last 3 years identified 238
      patients with flap tears, of which ultimately 58 with isolated flap tears were
      included after exclusion of patients with other significant knee internal
      derangement, severe degenerative change or prior surgery. MR studies of the knee
      were analyzed by two radiologists. Imaging characteristics were correlated with
      associated knee abnormalities and clinical findings. Statistical analysis
      employed linear and logistic regression models. Inter- and intrareader
      reliability was calculated. RESULTS: The medial meniscus was the most common site
      of flap tears (52/60, 87 %), with inferior displacement (47/60, 78 %). The degree
      of tibial cartilage loss had a positive correlation with the visual analog pain
      scale (p = 0.03). Patients who underwent arthroscopy were younger than those who
      did not (p = 0.01) and more likely to have a positive clinical McMurray test (p =
      0.01). CONCLUSION: Medially and inferiorly displaced flap tears are the most
      common tear pattern. Those undergoing arthroscopy are more likely to have
      positive meniscal signs on clinical examination. A greater degree of cartilage
      loss involving the tibia on MR imaging was associated with increasing visual
      analog pain scores.

PMID- 25398363
TI  - Prevalence of vertical root fracture as the reason for tooth extraction in dental
      clinics.
AB  - OBJECTIVES: The aim of this study was to investigate the prevalence, by gender,
      of vertical root fracture (VRF) as the main reason for the extraction of
      permanent teeth in dental clinics in Tokyo. MATERIALS AND METHODS: Participating
      dentists were requested to provide information about extractions of permanent
      teeth they had performed from 1 January 2013 to 30 June 2013. The main reasons
      for extraction were categorized as follows: VRF, caries (horizontal root fracture
      included), periodontal disease and others. RESULTS: At a total of 24 clinics, 736
      teeth were extracted from 626 patients during the 6-month period. A total of 233
      teeth were extracted by VRF (31.7%), and 93.6% of these were endodontically
      treated teeth. Among non-vital extracted teeth, 82.1% (179/218) had cast posts or
      screw posts. The percentage of extraction due to VRF was 29.4% in males and 34.7%
      in females. In females, the percentage of extractions due to VRF (34.7%) was
      higher than for periodontal disease (28.1%). In males, the percentage of
      extractions due to VRF increased with age (p < 0.05). The tooth types with the
      highest percentage of extractions due to VRF were the upper canine (46.7%), lower
      second premolar (48.0%) and lower first molar (50.0%) in males and the upper
      first premolar (43.3%), upper second premolar (44.4%), lower second premolar
      (53.8%) and lower first molar (54.5%) in females. CONCLUSIONS: These results
      indicate that we need to pay more attention to maintaining vital teeth while
      being aware of the particular tooth types in which VRF most frequently occurs.

PMID- 25398364
TI  - Competition of RNA splicing: line in or circle up.

PMID- 25398365
TI  - Early dental epithelial transcription factors distinguish ameloblastoma from
      keratocystic odontogenic tumor.
AB  - The aim of the study was to characterize the molecular relationship between
      ameloblastoma and keratocystic odontogenic tumor (KCOT) by means of a genome-wide
      expression analysis. Total RNA from 27 fresh tumor samples of 15
      solid/multicystic intraosseous ameloblastomas and 12 sporadic KCOTs was
      hybridized on Affymetrix whole genome arrays. Hierarchical clustering separated
      ameloblastomas and KCOTs into 2 distinct groups. The gene set enrichment analysis
      based on 303 dental genes showed a similar separation of ameloblastomas and
      KCOTs. Early dental epithelial markers PITX2, MSX2, DLX2, RUNX1, and ISL1 were
      differentially overexpressed in ameloblastoma, indicating its dental identity.
      Also, PTHLH, a hormone involved in tooth eruption and invasive growth, was one of
      the most differentially upregulated genes in ameloblastoma. The most
      differentially overexpressed genes in KCOT were squamous epithelial
      differentiation markers SPRR1A, KRTDAP, and KRT4, as well as DSG1, a component of
      desmosomal cell-cell junctions. Additonally, the epithelial stem cell marker SOX2
      was significantly upregulated in KCOT when compared with ameloblastoma. Taken
      together, the gene expression profile of ameloblastoma reflects differentiation
      from dental lamina toward the cap/bell stage of tooth development, as indicated
      by dental epithelium-specific transcription factors. In contrast, gene expression
      of KCOT indicates differentiation toward keratinocytes. 

PMID- 25398366
TI  - Systematic review on noninvasive treatment of root caries lesions.
AB  - The present systematic review critically summarizes results of clinical studies
      investigating chemical agents to reduce initiation or inactivation of root caries
      lesions (RCLs). Outcomes were DMFRS/DFRS (decayed, missing, filled root
      surfaces), surface texture (hard/soft), and/or RCI (root caries index). Three
      electronic databases were screened for studies from 1947 to 2014. Cross
      referencing was used to further identify articles. Article selection and data
      abstraction were done in duplicate. Languages were restricted to English and
      German. Mean differences (MD) were calculated for changes in DMFRS/DFRS. Risk
      ratios (RR) were calculated for changes in surface texture and RCI in a random
      effects model. Thirty-four articles with 1 or more agents were included; they
      reported 30 studies with 10,136 patients who were 20 to 101 y old; and they
      analyzed 28 chemical agents (alone or in combination). Eleven studies
      investigated dentifrices, 10 rinses, 8 varnishes, 3 solutions, 3 gels, and 2
      ozone applications. Meta-analyses revealed that dentifrices containing 5,000 ppm
      F(-) (RR = 0.49; 95% confidence interval [95% CI] = 0.42, 0.57; high level of
      evidence) or 1.5% arginine plus 1,450 ppm F(-) (RR = 0.79; 95% CI = 0.64, 0.98;
      very low level) are more effective in inactivating RCLs than dentifrices
      containing 1,100 to 1,450 ppm F(-). Self-applied AmF/SnF2-containing dentifrice
      and rinse decreased the initiation of RCLs when compared with NaF products
      (standardized MD = 0.15; 95% CI = -0.22, 0.52; low level). Patients rinsing with
      a mouth rinse containing 225 to 900 ppm F(-) revealed a significantly reduced
      DMFRS/DFRS (MD = -0.18; 95% CI = -0.35, -0.01; low level) when compared with a
      placebo rinse. Significantly reduced RCI was found for CHX (MD = -0.67; 95% CI = 
      1.01, -0.32; very low level) as well as SDF (MD = -0.33; 95% CI = -0.39, -0.28;
      very low level) when compared with placebo varnish. Regular use of dentifrices
      containing 5,000 ppm F(-) and quarterly professionally applied CHX or SDF
      varnishes seem to be efficacious to decrease progression and initiation of root
      caries, respectively. However, this conclusion is based on only very few well
      conducted randomized controlled trials. 

PMID- 25398367
TI  - Myopericytoma around the knee: mimicking a neurogenic tumour.
AB  - Myopericytoma is a rare, usually benign soft tissue tumour that arises most
      commonly in the dermis and subcutaneous soft tissue of the lower extremities. In
      this article, we present an unusual case of myopericytoma occurring in the deep
      soft tissue around the knee that mimicked a neurogenic tumour. Myopericytoma can
      be confused with neurogenic tumour when located in deep soft tissue and adjacent
      to nerve bundles. Preoperative MRI and colour Doppler ultrasound may help
      differentiate myopericytoma from neurogenic tumour by revealing the hypervascular
      nature of the tumour. 

PMID- 25398368
TI  - Magnetic resonance imaging characterization of individual ankle syndesmosis
      structures in asymptomatic and surgically treated cohorts.
AB  - PURPOSE: Historically, syndesmosis injuries have been underdiagnosed. The purpose
      of this study was to characterize the 3.0-T MRI presentations of the distal
      tibiofibular syndesmosis and its individual structures in both asymptomatic and
      injured cohorts. METHODS: Ten age-matched asymptomatic volunteers were imaged to
      characterize the asymptomatic syndesmotic anatomy. A series of 21 consecutive
      patients with a pre-operative 3.0-T ankle MRI and subsequent arthroscopic
      evaluation for suspected syndesmotic injury were reviewed and analysed.
      Prospectively collected pre-operative MRI findings were correlated with
      arthroscopy to assess diagnostic accuracy [sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV)]. RESULTS: Pathology
      diagnosed on pre-operative MRI correlated strongly with arthroscopic findings.
      Syndesmotic ligament disruption was prospectively diagnosed on MRI with excellent
      sensitivity, specificity, PPV, NPV, and accuracy: anterior inferior tibiofibular
      ligament (87.5, 100, 100, 71.4, 90.5 %); posterior inferior tibiofibular ligament
      (N/A, 95.2, 0.0, 100, 95.2 %); and interosseous tibiofibular ligament (66.7,
      86.7, 66.7, 86.7, 81.0 %). CONCLUSIONS: Pre-operative 3.0-T MRI demonstrated
      excellent accuracy in the diagnosis of syndesmotic ligament tears and allowed for
      the visualization of relevant individual syndesmosis structures. Using a standard
      clinical ankle MRI protocol at 3.0-T, associated ligament injuries could be
      readily identified. Clinical implementation of optimal high-field MRI sequences
      in a standard clinical ankle MRI exam can aid in the diagnosis of syndesmotic
      injuries, augment pre-operative planning, and facilitate anatomic repair by
      providing additional details regarding the integrity of individual syndesmotic
      structures not discernible through physical examination and radiographic
      assessments. LEVEL OF EVIDENCE: II.

PMID- 25398369
TI  - The effects of the sagittal plane malpositioning of the patella and concomitant
      quadriceps hypotrophy on the patellofemoral joint: a finite element analysis.
AB  - PURPOSE: Anterior knee pain is a common symptom after intramedullary nailing in
      tibia shaft fracture. Moreover, patellofemoral malalignment is also known to be a
      major reason for anterior knee pain. Patellofemoral malalignment predisposes to
      increased loading in patellar cartilage. In the previous study, we have
      demonstrated the quadriceps atrophy and patellofemoral malalignment after
      intramedullary nailing due to tibia shaft fracture. In this study, our aim was to
      clarify the effects of quadriceps atrophy and patellofemoral malalignment with
      the pathologic loading on the joint cartilage. METHODS: Mesh models of
      patellofemoral joint were constructed with CT images and integrated with soft
      tissue components such as menisci and ligaments. Physiological and sagittal tilt
      models during extension and flexion at 15 degrees , 30 degrees  and 60 degrees 
      were created generating eight models. All the models were applied with 137 N
      force to present the effects of normal loading and 115.7 N force for the
      simulation of quadriceps atrophy. Different degrees of loading were applied to
      evaluate the joint contact area and pressure value with the finite element
      analysis. RESULTS: There was increased patellofemoral contact area in patellar
      tilt models with respect to normal models. The similar loading patterns were
      diagnosed in all models at 0 degrees  and 15 degrees  knee flexion when 137 N
      force was applied. Higher loading values were obtained at 30 degrees  and 60
      degrees  knee flexions in sagittal tilt models. Furthermore, in the sagittal tilt
      models, in which the quadriceps atrophy was simulated, the loadings at 30 degrees
      and 60 degrees  knee flexion were higher than in the physiological ones.
      CONCLUSIONS: Sagittal malalignment of the patellofemoral joint is a new concept
      that results in different loading patterns in the patellofemoral joint
      biomechanics. This malalignment in sagittal plane leads to increased loading
      values on the patellofemoral joint at 30 degrees  and 60 degrees  of the knee
      flexions. This new concept should be kept in mind during the course of diagnosis
      and treatment in patients with anterior knee pain. Definition of the exact
      biomechanical effects of the sagittal tilting will lead to the development of new
      treatment modalities.

PMID- 25398370
TI  - Resisting religious coercive control.
AB  - Religious coercive control refers to the use of religious beliefs and doctrine as
      means to coercively control intimate partners. Scholars have shown that some
      abusive partners use the Christian doctrine of submission as a means of religious
      coercive control. I explore how victims who experience the doctrine of submission
      qua religious coercive control actively resist it. I argue that victims'
      successful resistance of the doctrine is contingent on their religious capital
      that is, the knowledge and mastery that people have of a particular religious
      culture-and interpretive confidence-that is, people's subjective confidence in
      their interpretations of religious culture-related to the doctrine. 

PMID- 25398371
TI  - Factors increasing the likelihood of sole and dual charging of women for intimate
      partner violence.
AB  - Sole and dual charging of women for intimate partner violence (IPV) has risen in
      some Canadian and American jurisdictions since the implementation of pro-charging
      policies. Adding to the limited research within Canada by examining court cases
      from a small, Ontario city, sociodemographic and situational characteristics are
      assessed to determine if the context in which women were charged differs from
      that of men, or in which dual charges were laid. Women were more likely to be
      charged if they were younger, in legal or common-law relationships, and in rural
      jurisdictions. Dual charging was more likely among women in current and dating
      relationships. 

PMID- 25398372
TI  - Angiotensin receptor blocker in patients with ST segment elevation myocardial
      infarction with preserved left ventricular systolic function: prospective cohort
      study.
AB  - OBJECTIVE: To investigate the association between treatment with an angiotensin
      receptor blocker and clinical outcomes in patients with ST segment elevation
      myocardial infarction with preserved left ventricular systolic function. DESIGN:
      A prospective cohort study using data from a nationwide large scale registry.
      SETTING: 53 hospitals involved in treatment of acute myocardial infarction in
      Korea. PARTICIPANTS: Between November 2005 and September 2010, we studied 6698
      patients with ST segment elevation myocardial infarction who underwent primary
      percutaneous coronary intervention and had a left ventricular ejection fraction
      >= 40%. MAIN OUTCOME MEASURES: Cardiac death or myocardial infarction. Patients
      were divided into an angiotensin receptor blocker group (n=1185), an angiotensin
      converting enzyme (ACE) inhibitor group (n=4564), and a group who did not receive
      any renin angiotensin system blocker (n=949). Propensity score matching analysis
      was also performed. RESULTS: Cardiac death or myocardial infarction occurred in
      21 patients (1.8%) in the angiotensin receptor blocker group, 77 patients (1.7%)
      in the ACE inhibitor group, and 33 patients (3.5%) in the no renin angiotensin
      system blocker group. After propensity score matching (1175 pairs), there was no
      significant difference in the rate of cardiac death or myocardial infarction
      between the angiotensin receptor blocker group and ACE inhibitor group (21 (1.8%)
      v 23 (2.0%), adjusted hazard ratio 0.65, 95% confidence interval 0.30 to 1.38;
      P=0.65). The angiotensin receptor blocker group had a lower rate of cardiac death
      or myocardial infarction than the no renin angiotensin system blocker group in
      matched populations (803 pairs) (14 (1.7%) v 25 (3.1%), 0.35, 0.14 to 0.90;
      P=0.03). CONCLUSION: Angiotensin receptor blocker showed beneficial effects
      comparable with ACE inhibitors in patients with ST segment elevation myocardial
      infarction with preserved left ventricular systolic function. Angiotensin
      receptor blockers could be used as an alternative to ACE inhibitors in such
      patients.

PMID- 25398373
TI  - Conservation analysis of residues in the S4-S5 linker and the terminal part of
      the S5-P-S6 pore modulus in Kv and HCN channels: flexible determinants for the
      electromechanical coupling.
AB  - Protein mobility is important to achieve protein function. Intrinsic flexibility
      associated with motion underlies this important issue and the analysis of side
      chain flexibility gives insights to understand it. In this work, the S5-P-S6 pore
      modulus (PM) of members of Kv and HCN channels was examined by a combination of
      sequence alignment, residue composition analysis, and intrinsic side chain
      flexibility. The PM sequences were organized as a database that was used to
      reveal and correlate the functional diversity of each analyzed family.
      Specifically, we focused our attention on the crucial role of the S4-S5 linker
      and its well-described interaction with the S6 T during the electromechanical
      coupling. Our analysis suggests the presence of a Gly-hinge in the middle of the
      S4-S5 linkers. This apparent Gly-hinge links a flexible N-terminal segment with a
      rigid C-terminal one, although in Kv7 channels, the latter segment is even more
      flexible. Instead, HCN channels exhibit a putative Thr-hinge and is rich in
      aromatic residues, in consequence, their linker is more rigid. Concerning S6, we
      confirm the presence of the two flexible kinks previously described and we
      provide the complete segmental flexibility profiles for the different families.
      Our results are discussed in terms of the relation between residue composition,
      conservation, and local conformational flexibility. This provides important
      insights to understand and differentiate the characteristic gating properties of
      these channels as well as their implications in cell physiology. 

PMID- 25398374
TI  - The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in
      rheumatoid arthritis.
AB  - OBJECTIVE: Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment
      of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the
      effects on gene expression in situ are unknown. Therefore, tofacitinib effects on
      synovial pathobiology were investigated. METHODS: A randomised, double-blind,
      phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA
      with an inadequate methotrexate response. Patients on background methotrexate
      received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies
      were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR.
      Clinical response was determined by disease activity score and European League
      Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a
      long-term extension study (A3921024; NCT00413699). RESULTS: Tofacitinib exposure
      led to EULAR moderate to good responses (11/14 patients), while placebo was
      ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly
      reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3
      (p<0.05) and chemokines CCL2, CXCL10 and CXCL13 (p<0.05). No overall changes were
      observed in synovial inflammation score or the presence of T cells, B cells or
      macrophages. Changes in synovial phosphorylation of signal transducer and
      activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month
      clinical responses (p<0.002). Tofacitinib significantly decreased plasma CXCL10
      (p<0.005) at Day 28 compared with placebo. CONCLUSIONS: Tofacitinib reduces
      metalloproteinase and interferon-regulated gene expression in rheumatoid
      synovium, and clinical improvement correlates with reductions in STAT1 and STAT3
      phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely
      play a key role in the synovial response. TRIAL REGISTRATION NUMBER: NCT00976599.

PMID- 25398375
TI  - Comorbidities in patients with gout prior to and following diagnosis: case
      control study.
AB  - OBJECTIVES: To determine the burden of comorbidities in patients with gout at
      diagnosis and the risk of developing new comorbidities post diagnosis. METHODS:
      There were 39 111 patients with incident gout and 39 111 matched controls
      identified from the UK Clinical Practice Research Data-link. The risk of
      comorbidity before (ORs) and after the diagnosis of gout (HRs) were estimated,
      adjusted for age, sex, diagnosis year, body mass index, smoking and alcohol
      consumption. RESULTS: Gout was associated with adjusted ORs (95% CIs) of 1.39
      (1.34 to 1.45), 1.89 (1.76 to 2.03) and 2.51 (2.19 to 2.86) for the Charlson
      index of 1-2, 3-4 and >=5, respectively. Cardiovascular and genitourinary
      diseases, in addition to hyperlipidaemia, hypothyroidism, anaemia, psoriasis,
      chronic pulmonary diseases, osteoarthritis and depression, were associated with a
      higher risk for gout. Gout was also associated with an adjusted HR (95% CI) of
      1.41 (1.34 to 1.48) for having a Charlson index >=1. Median time to first
      comorbidity was 43 months in cases and 111 months in controls. Risks for incident
      comorbidity were higher in cardiovascular, genitourinary, metabolic/endocrine and
      musculoskeletal diseases, in addition to liver diseases, hemiplegia, depression,
      anaemia and psoriasis in patients with gout. After additionally adjusting for all
      comorbidities at diagnosis, gout was associated with a HR (95% CI) for all-cause
      mortality of 1.13 (1.08 to 1.18; p<0.001). CONCLUSIONS: The majority of patients
      with gout have worse pre-existing health status at diagnosis and the risk of
      incident comorbidity continues to rise following diagnosis. The range of
      associated comorbidities is broader than previously recognised and merits further
      evaluation.

PMID- 25398376
TI  - Dynamics of the establishment of multinucleate compartments in Fusarium
      oxysporum.
AB  - Nuclear dynamics can vary widely between fungal species and between stages of
      development of fungal colonies. Here we compared nuclear dynamics and mitotic
      patterns between germlings and mature hyphae in Fusarium oxysporum. Using
      fluorescently labeled nuclei and live-cell imaging, we show that F. oxysporum is
      subject to a developmental transition from a uninucleate to a multinucleate state
      after completion of colony initiation. We observed a special type of hypha that
      exhibits a higher growth rate, possibly acting as a nutrient scout. The higher
      growth rate is associated with a higher nuclear count and mitotic waves involving
      2 to 6 nuclei in the apical compartment. Further, we found that dormant nuclei of
      intercalary compartments can reenter the mitotic cycle, resulting in
      multinucleate compartments with up to 18 nuclei in a single compartment. 

PMID- 25398377
TI  - Medication overuse headache.
AB  - Medication overuse headache (MOH) is a common and disabling headache disorder. It
      has a prevalence of about 1-2 % in the general population. The International
      Classification of Headache Disorders 3rd edition (beta version) has defined MOH
      as a chronic headache disorder in which the headache occurs on 15 or more days
      per month due to regular overuse of medication. These headaches must have been
      present for more than 3 months. The pathophysiology is complex and not completely
      known. It involves genetic and behavioural factors. There is evidence that
      cortical spreading depression, trigeminovascular system and neurotransmitters
      contribute to the pain pathway of MOH. The treatment of MOH includes patient
      education, stopping the offending drug(s), rescue therapy for withdrawal symptoms
      and preventative therapy. Relapse rates for MOH are high at 41 %. MOH can
      severely impact quality of life, so it is important to identify patients who are
      at risk of analgesic overuse.

PMID- 25398379
TI  - Recording occupation in general practice--a second cycle audit.
AB  - BACKGROUND: An audit of working age patients' records in two Cornish general
      practices in 2012 found infrequent and inconsistent recording of patients'
      occupations. A concurrent survey of general practitioners (GPs) in Cornwall found
      that a majority of them believed it was important to do so. AIMS: To review
      occupation recording in the same practices a year later and to audit a third
      practice, following the introduction of the electronic fit note. To repeat the
      survey of attitudes to recording occupation in GPs in Cornwall. METHODS: We
      manually checked 300 randomly selected patient records in Practice A and
      electronically searched all records of working age patients (aged 16-65 years) in
      Practices B and C for recorded occupation. We sent an electronic survey of
      attitudes to recording occupation to 202 GPs in Cornwall. RESULTS: Recording of
      occupation increased from 17 to 30% of records (chi(2) = 15, P < 0.001) in
      Practice A and from 12 to 14% (chi(2) = 16.5, P < 0.001) in Practice B. In
      Practice C, 1% of records had occupation recorded and coded. The proportion of
      GPs in Cornwall who said that it is important to records patients' occupation
      increased from 70 to 90% (Fisher's exact statistic 0.01, P < 0.05). CONCLUSIONS:
      Recording of patients' occupation increased in both practices from 2012 to 2013,
      but remains infrequent and inconsistent and the very low levels in a third
      practice not previously audited is of concern.

PMID- 25398378
TI  - An update and review of the treatment of myoclonus.
AB  - Recent advances in medications and surgical therapy for neurological disorders
      may offer new therapeutic options for the treatment of myoclonus. Appropriate
      therapy for myoclonus depends on the etiology, and in some cases, myoclonus can
      improve when the provoking cause is eliminated. When the underlying cause for the
      movements is not immediately reversible, localization, disease pathophysiology,
      and etiology may each play a role in determining the most appropriate symptomatic
      treatment of disabling myoclonic jerks. While the use of many agents is still
      based on small, open-label case series and anecdotes, there is a growing body of
      evidence from head-to-head comparative trials in several types of myoclonus that
      may help guide therapy. New therapies for refractory myoclonus, including sodium
      oxybate and even deep brain stimulation, are also being explored with increasing
      enthusiasm. 

PMID- 25398380
TI  - Molecular characterization of plasmid pMoma1of Moraxella macacae, a newly
      described bacterial pathogen of macaques.
AB  - We report the complete nucleotide sequence and characterization of a small
      cryptic plasmid of Moraxella macacae 0408225, a newly described bacterial species
      within the family Moraxellaceae and a causative agent of epistaxis in macaques.
      The complete nucleotide sequence of the plasmid pMoma1 was determined and found
      to be 5,375 bp in size with a GC content of 37.4 %. Computer analysis of the
      sequence data revealed five open reading frames encoding putative proteins of
      54.4 kDa (ORF1), 17.6 kDa (ORF2), 13.3 kDa (ORF3), 51.6 kDa (ORF4), and 25.0 kDa
      (ORF5). ORF1, ORF2, and ORF3 encode putative proteins with high identity (72, 42,
      and 55 %, respectively) to mobilization proteins of plasmids found in other
      Moraxella species. ORF3 encodes a putative protein with similarity (about 40 %)
      to several plasmid replicase (RepA) proteins. The fifth open reading frames (ORF)
      was most similar to hypothetical proteins with unknown functions, although domain
      analysis of this sequence suggests it belongs to the Abi-like protein family.
      Upstream of the repA gene, a 470-bp intergenic region, was identified that
      contained an AT-rich section and two sets of tandem direct and indirect repeats,
      consistent with a putative origin of replication site. In contrast to other
      plasmids of Moraxella, the occurrence of pMoma1 in M. macacae isolates appears to
      be common as PCR testing of 14 clinical isolates from two different research
      institutions all contained the plasmid.

PMID- 25398381
TI  - Ethical and Professional Challenges Encountered by Laboratory Genetic Counselors.
AB  - Laboratory-based genetic counseling is a growing and yet under researched
      specialty. In this study, 111 laboratory-based genetic counselors employed in
      various settings (commercial, academic, etc.) completed an online survey
      assessing demographics and frequency of encountering 16 domains of ethical and
      professional challenges encountered by clinical genetic counselors defined
      previously by McCarthy Veach et al. and validated by Bower et al. Forty-nine of
      the laboratory genetic counselors also provided anecdotes of particularly
      challenging situations and strategies for their resolution. Most respondents had
      less than 5 years' experience as laboratory counselors (71 %), worked full-time
      (75 %) in industry-based laboratories (91 %) with a focus on molecular
      diagnostics (84 %), and had limited patient contact (91 %). Similar to clinical
      counselors, every ethical and professional challenge was endorsed as occurring
      frequently by some respondents. The most common frequently occurring domains for
      the sample were: facing uncertainty, time and financial resource allocation,
      attaining and maintaining proficiency, and informed consent. Content analysis of
      respondents' anecdotes yielded themes that most commonly concerned: professional
      identity issues, value conflicts, confidentiality, and colleague error. One
      unique domain labeled professional communication (educating professionals with
      limited genetics knowledge), and three salient categories within the professional
      identity domain--gatekeeping, conflicts of interest, and professional image--were
      extracted from the anecdotes. The most prevalent strategy for resolving
      challenging situations was inform health care professional. Results suggest
      laboratory-based genetic counselors generally face similar ethical and
      professional challenges as clinical genetic counselors but their exact nature and
      relative frequency differ. These findings contribute to a greater understanding
      of common and unique experiences of genetic counselors in different professional
      specialties.

PMID- 25398382
TI  - Outcomes assessed in trials of gout and accordance with OMERACT-proposed domains:
      a systematic literature review.
AB  - OBJECTIVE: The aim of this study was to systematically review outcome domains and
      measurement tools used in gout trials and their accordance with the preliminary
      OMERACT gout recommendations published in 2005. METHODS: Randomized controlled
      trials (RCTs) and quasi-RCTs investigating any intervention for gout published up
      to February 2013 were included. Recruitment start dates and all measured outcomes
      were extracted. Risk of bias (RoB) was assessed with the Cochrane Collaboration
      tool. Numbers of OMERACT domains were compared for trials at low vs unclear/high
      RoB and for recruitment start date before 2005 or 2005 and later. RESULTS: Of
      9784 articles screened, 38 acute and 30 chronic gout trials were included. Mean
      (s.d.) number of OMERACT outcomes was 2.9 (1.1) (out of 5) and 2.5 (1.2) (out of
      9) for acute and chronic gout trials, respectively. Health-related quality of
      life, participation and joint damage imaging were not assessed in any trial.
      Tools used to measure individual domains varied widely. There were no differences
      in the number of OMERACT outcomes reported in acute or chronic gout trials
      recruiting before 2005 vs 2005 or later [mean (s.d.): 3.0 (1.1) vs 3.5 (1.3), P =
      0.859 and 2.7 (1.1) vs 2.8 (1.4), P = 0.960, respectively]. While both acute and
      chronic trials at low RoB reported more OMERACT domains than trials at
      unclear/high RoB, these differences were not significant. Industry-funded trials
      and trials performed by OMERACT investigators reported more OMERACT outcome
      domains. CONCLUSION: We found no appreciable impact of the OMERACT
      recommendations for gout trials to date.

PMID- 25398384
TI  - The development of family nursing in Denmark: current status and future
      perspectives.
AB  - Over the past 12 years, a strong foundation for family nursing has been built in
      Denmark, with rapid growth in the past 3 years. A review of nursing research
      conducted in Denmark and published between 2002 and 2013 found 15 studies that
      examined family phenomena. The majority of the studies used descriptive methods
      with data collected from surveys and interviews involving family members either
      together or individually. Only five of the studies examined interventions that
      included families' perspectives about the intervention being evaluated. Several
      current research projects lead by Danish nurses examine the implementation of
      family nursing knowledge to clinical settings. Integration of family nursing
      theory has begun in Denmark in undergraduate and graduate nursing curricula and
      in May 2013, the Danish Family Nursing Association was officially established.
      Infrastructure and financial conference support has made it possible to invite
      Nordic and international colleagues to meet in Denmark, which, reciprocally,
      expands understanding and support for family nursing within the country. Further
      collaboration between Danish nurse researchers, educators, and administrators
      will help sustain the growth of family nursing science and its application in
      family-focused nursing practice. 

PMID- 25398383
TI  - Cytokine responses to Staphylococcus aureus bloodstream infection differ between
      patient cohorts that have different clinical courses of infection.
AB  - BACKGROUND: The clinical course of Staphylococcus aureus bloodstream infection is
      unpredictable and bacterial virulence, host immune response and patient
      characteristics are among the factors that contribute to the clinical course of
      infection. To investigate the relationship between cytokine response and clinical
      outcome, circulating cytokine levels were investigated in response to S. aureus
      bloodstream infection in patients with different clinical courses of infection.
      METHODS: A prospective study was carried out in 61 patients with S. aureus
      bloodstream infection and circulating levels of IL-6, GRO-gamma, RANTES and
      leptin were assessed over the course of the infection. Levels were compared in
      patients with complicated courses of infection (e.g. infective endocarditis)
      versus uncomplicated courses of S. aureus bloodstream infection and methicillin
      resistant S. aureus Vs methicillin-susceptible S. aureus infection. RESULTS:
      Significantly lower leptin levels (p < 0.05) and significantly higher IL-6 levels
      (p < 0.05) were detected at laboratory diagnosis in patients with complicated
      compared to uncomplicated S. aureus bloodstream infection. Significantly higher
      levels of GRO-gamma were associated with MRSA infection compared to MSSA
      infection. CONCLUSIONS: IL-6 may be an early inflammatory marker of complicated
      S. aureus bloodstream infection. Leptin may be protective against the development
      of a complicated S. aureus bloodstream infection.

PMID- 25398387
TI  - [Obituary Prof. Dr. med. Heinz Becker].

PMID- 25398385
TI  - Loss of endothelial-ARNT in adult mice contributes to dampened circulating
      proangiogenic cells and delayed wound healing.
AB  - The recruitment and homing of circulating bone marrow-derived cells include
      endothelial progenitor cells (EPCs) that are critical to neovascularization and
      tissue regeneration of various vascular pathologies. We report here that
      conditional inactivation of hypoxia-inducible factor's (HIF) transcriptional
      activity in the endothelium of adult mice (Arnt(DeltaiEC) mice) results in a
      disturbance of infiltrating cells, a hallmark of neoangiogenesis, during the
      early phases of wound healing. Cutaneous biopsy punches show distinct migration
      of CD31(+) cells into wounds of control mice by 36 hours. However, a significant
      decline in numbers of infiltrating cells with immature vascular markers, as well
      as decreased transcript levels of genes associated with their expression and
      recruitment, were identified in wounds of Arnt(DeltaiEC) mice. Matrigel plug
      assays further confirmed neoangiogenic deficiencies alongside a reduction in
      numbers of proangiogenic progenitor cells from bone marrow and peripheral blood
      samples of recombinant vascular endothelial growth factor-treated Arnt(DeltaiEC)
      mice. In addition to HIF's autocrine requirements in endothelial cells, our data
      implicate that extrinsic microenvironmental cues provided by endothelial HIF are
      pivotal for early migration of proangiogenic cells, including those involved in
      wound healing. 

PMID- 25398386
TI  - Nck1 depletion induces activation of the PI3K/Akt pathway by attenuating PTP1B
      protein expression.
AB  - BACKGROUND: Activation of the PI3K/Akt pathway mediates crucial cellular
      functions regulated by receptor tyrosine kinases, such as cell growth,
      proliferation, survival and metabolism. Previously, we reported that the whole
      body knockout of the Src homology domain-containing adaptor protein Nck1 improves
      overall glucose homeostasis and insulin-induced activation of the PI3K/Akt
      pathway in liver of obese mice. The aim of the current study is to elucidate the
      mechanism by which Nck1 depletion regulates hepatic insulin signaling. RESULTS:
      Here, we demonstrate that Nck1 regulates the activation of the PI3K/Akt pathway
      in a protein tyrosine phosphatase 1B (PTP1B)-dependent mechanism. Indeed,
      depletion of Nck1 by siRNA in HepG2 cells enhances PI3K-dependent basal and
      growth factor-induced Akt activation. In accordance, primary hepatocytes isolated
      from Nck1 (-/-) mice also display enhanced Akt activation in response to insulin.
      Activation of the PI3K/Akt pathway in Nck1-depleted HepG2 cells relies on higher
      levels of tyrosine-phosphorylated proteins and correlates with decreased PTP1B
      levels. Interestingly, Nck1 and PTP1B in cells are found in a common molecular
      complex and their interaction is dependent on the SH3 domains of Nck1. Finally,
      Nck1 depletion in HepG2 cells neither affects PTP1B gene transcription nor PTP1B
      protein stability, suggesting that Nck1 modulates PTP1B expression at the
      translational level. CONCLUSION: Our study provides strong evidence supporting
      that the adaptor protein Nck1 interacts with PTP1B and also regulates PTP1B
      expression. In this manner, Nck1 plays a role in regulating the PI3K/Akt pathway.

PMID- 25398388
TI  - Curricular priorities for business ethics in medical practice and research:
      recommendations from Delphi consensus panels.
AB  - BACKGROUND: No published curricula in the area of medical business ethics exist.
      This is surprising given that physicians wrestle daily with business decisions
      and that professional associations, the Institute of Medicine, Health and Human
      Services, Congress, and industry have issued related guidelines over the past 5
      years. To fill this gap, the authors aimed (1) to identify the full range of
      medical business ethics topics that experts consider important to teach, and (2)
      to establish curricular priorities through expert consensus. METHODS: In spring
      2012, the authors conducted an online Delphi survey with two heterogeneous panels
      of experts recruited in the United States. One panel focused on business ethics
      in medical practice (n = 14), and 1 focused on business ethics in medical
      research (n = 12). RESULTS: Panel 1 generated an initial list of 14 major topics
      related to business ethics in medical practice, and subsequently rated 6 topics
      as very important or essential to teach. Panel 2 generated an initial list of 10
      major topics related to business ethics in medical research, and subsequently
      rated 5 as very important or essential. In both domains, the panel strongly
      recommended addressing problems that conflicts of interest can cause, legal
      guidelines, and the goals or ideals of the profession. CONCLUSIONS: The Bander
      Center for Medical Business Ethics at Saint Louis University will use the results
      of the Delphi panel to develop online curricular resources for each of the
      highest rated topics.

PMID- 25398390
TI  - Extreme ("pathological") demand avoidance in autism: a general population study
      in the Faroe Islands.
AB  - Research into Pathological Demand Avoidance (PDA), which has been suggested to be
      a subgroup within the Autism Spectrum Disorder (ASD), is almost nonexistent in
      spite of the frequent reference to the condition in clinical practice. The total
      population of 15 to 24-year-olds in the Faroe Islands was screened for ASD, and
      67 individuals were identified who met diagnostic criteria for ASD (corresponding
      to a general population prevalence of ASD of almost 1 %). Of these 67, 50 had
      parents who were interviewed using the Diagnostic Interview for Social and
      Communication Disorders (DISCO-11) which contains 15 "PDA-specific" items. Nine
      individuals met criteria for "possible clinical diagnosis of PDA", meaning that
      almost one in five of all with ASD also had indications of having had PDA in
      childhood, and that 0.18 % of the total population had had the combination of ASD
      and PDA. However, at the time of assessment, only one of the 9 individuals with
      possible PDA still met "full criteria". PDA possibly constitutes a considerable
      minority of all cases with ASD diagnosed in childhood, but criteria for the
      condition are unlikely to be still met in later adolescence and early adult life.

PMID- 25398389
TI  - [Vancouver classification of renal tumors: Recommendations of the 2012 consensus
      conference of the International Society of Urological Pathology (ISUP)].
AB  - The 2012 consensus conference of the International Society of Urological
      Pathology (ISUP) has formulated recommendations on classification, prognostic
      factors and staging as well as immunohistochemistry and molecular pathology of
      renal tumors. Agreement was reached on the recognition of five new tumor
      entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease
      associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription
      factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis
      associated RCC. In addition three rare forms of carcinoma were considered as
      emerging or provisional entities: thyroid-like follicular RCC, succinate
      dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK)
      translocation RCC. In the new ISUP Vancouver classification, modifications to the
      existing 2004 World Health Organization (WHO) specifications are also suggested.
      Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor
      necrosis were emphasized as being significant prognostic parameters for RCC. The
      consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3
      due to nucleolar prominence and grade 4 is reserved for cases with extreme
      nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore,
      consensus guidelines were established for the preparation of samples. For
      example, agreement was also reached that renal sinus invasion is diagnosed when
      the tumor is in direct contact with the fatty tissue or loose connective tissue
      of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within
      the renal sinus are invaded by the tumor, independent of the size. The importance
      of biomarkers for the diagnostics or prognosis of renal tumors was also
      emphasized and marker profiles were formulated for use in specific differential
      diagnostics. 

PMID- 25398392
TI  - A systematic review and meta-analysis comparing immediate and delayed catheter
      removal following uncomplicated hysterectomy.
AB  - BACKGROUND: The use of an indwelling catheter after uncomplicated hysterectomy is
      common, but remains controversial because of the occurrence of catheter
      associated urinary tract infections (UTIs) and discomfort. OBJECTIVE: To examine
      the evidence on the benefits and harm from the use of an indwelling catheter
      after uncomplicated hysterectomy. DESIGN: Systematic review and meta-analysis of
      randomized controlled trials (RCTs). DATA SOURCES: Electronic databases including
      PubMed, Embase, the Cochrane Library, and Science Citation Index up to July 2014
      were searched for relevant RCTs and the reference lists of the included studies
      were also searched manually. REVIEW METHODS: Included studies were RCTs comparing
      immediate and delayed catheter removal following uncomplicated hysterectomy
      without concomitant pelvic floor surgery. Two independent reviewers identified
      relevant RCTs, assessed their methodological quality and extracted data. Mantel
      Haenszel estimates were calculated and pooled using a fixed or random effects
      model data are expressed as relative risks (RRs) and 95% confidence intervals
      (CIs). RESULTS: Ten RCTs with a total of 1,188 patients that met the inclusion
      criteria were analysed. Early catheter removal was associated with a reduced risk
      of positive urine culture (RR 0.60, 95% CI 0.40 to 0.88) and symptomatic UTI (RR
      0.23, 95% CI 0.10 to 0.52). However, the incidence of recatheterization was lower
      among patients with delayed catheter removal (RR 3.32, 95% CI 1.48 to 7.46).
      There was no significant difference in febrile morbidity associated with UTI
      between the two approaches (RR 0.38, 95% CI 0.11 to 1.36). In addition, delayed
      catheter removal was associated with a longer time to first ambulation (standard
      mean difference -2.73, 95% CI -4.00 to -1.47]. CONCLUSIONS: The existing evidence
      from RCTs suggests that delayed catheter removal following uncomplicated
      hysterectomy increases the incidence of postoperative bacteriuria and symptomatic
      UTI but reduces the risk of recatheterization.

PMID- 25398394
TI  - Parity of esteem between mental and physical health.

PMID- 25398396
TI  - Effect of thermal annealing on the thermoluminescent properties of nano-calcium
      fluoride and its dose-response characteristics.
AB  - Nano-CaF2, prepared by the co-precipitation method, was annealed under different
      annealing conditions to improve its thermoluminescence (TL) characteristics.
      Different annealing parameters, such as temperature (400-700 degrees C), duration
      (1-4 h) and environment (vacuum and air), were explored. The effect on TL
      sensitivity, peak position (Tm) and full-width at half-maximum (FWHM) with
      respect to the different annealing conditions are discussed as they are the
      measure of crystallinity of the material. Annealing temperature of 500 degrees C
      with annealing duration of two and a half hours in vacuum provided the highest
      luminescence response (i.e. maximum sensitivity, minimum peak temperature and
      FWHM). Wide detectable dose range (5 mGy to 2 kGy), absence of thermal quenching
      and sufficient activation energy (1.04 eV) of this phosphor make it suitable for
      dosimetric applications.

PMID- 25398395
TI  - The B" regulatory subunit of protein phosphatase 2A mediates the
      dephosphorylation of rice retinoblastoma-related protein-1.
AB  - The phosphorylation of plant retinoblastoma-related (RBR) proteins by cyclin
      dependent kinases (CDKs) is well documented, but the counteracting phosphatases
      have not been identified yet. We report here that rice retinoblastoma-related
      protein-1 (OsRBR1) interacted with the B" subunit of rice protein phosphatase 2A
      (OsPP2A B") and underwent reversible phosphorylation during the cell division
      cycle. The OsRBR1-OsPP2A B" association required B domain in OsRBR1 and the C
      terminal region of OsPP2A B". We found by immunoprecipitation that OsPP2A B",
      OsPP2A catalytic subunit subtype II, PSTAIRE-type CDK and OsRBR1 were in the same
      protein complex, indicating a physical association between the phosphatase, the
      kinase and their common substrate. OsPP2A B" contains three predicted CDK
      phosphorylation sites: Ser95, Ser102 and Ser119. The in vitro phosphorylation of
      Ser95 and Ser119 with PSTAIRE-kinases was verified by mass spectrometry. We
      generated a series of phosphorylation site mutants to mimic the dephosphorylated
      or phosphorylated states of OsPP2A B", and confirmed that all of the three
      predicted sites can be phosphorylated. Yeast two-hybrid experiments suggested
      that the phosphorylation of OsPP2A B" promoted the formation of the OsPP2A
      holoenzyme. A triple phosphorylation mimicking OsPP2A B" mutant containing
      holoenzyme showed higher activity in phosphatase assays. Our data collectively
      show that the phosphatase activity of OsPP2A against OsRBR1 is regulated by the
      phosphorylation of its B" regulatory subunit. However, the analysis of the effect
      of okadaic acid, a phosphatase inhibitor, in rice cell suspension cultures
      revealed that the dephosphorylation of OsRBR1 was completely inhibited only by
      high dose (300 nM) of the okadaic acid during the cell cycle progression.
      Therefore the role of the protein phosphatase 1 should be considered as an
      additional post translational regulatory component of RBR protein function in
      higher plants. 

PMID- 25398398
TI  - Effect of hyaluronan-enriched embryo transfer medium on IVF outcome: a
      prospective randomized clinical trial.
AB  - PURPOSE: This prospective randomized study reports the effect of hyaluronan
      enriched embryo transfer media on the outcome of in vitro fertilization and
      embryo transfer (IVF-ET) treatments. METHODS: A total of 581 IVF-ET cycles were
      included in this study. In the Hyaluronan (HA) group (n = 290), embryos were
      transferred from hyaluronan-enriched transfer medium. In Control group (n = 291),
      a conventional embryo transfer medium was used. RESULTS: There was no significant
      difference in clinical pregnancy rate (42.4 vs. 39.2%), implantation rate (23.3
      vs. 23.2%), and delivery rate (31.0 vs. 29.2%) between the HA group and the
      Control group. The number of newborns was also similar in the two groups (111 vs.
      110). However, birth weight was significantly higher in the HA group than in the
      Control group (3,018 +/- 598 g vs. 2,724 +/- 698 g, P = 0.001). Clinical
      pregnancy, implantation and delivery rates did not differ significantly between
      the HA and the Control group when cycles with advanced maternal age, previous IVF
      failures, low oocyte number or poor embryo quality were compared. CONCLUSION: Our
      results suggest that hyaluronan enrichment of the embryo transfer media does not
      seem to have any beneficial effect on IVF outcome. However, further study is
      needed to clarify the role of hyaluronan in the implantation process and on the
      birth weight.

PMID- 25398397
TI  - T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and
      ovarian carcinosarcomas overexpressing HER2.
AB  - Ovarian and uterine carcinosarcoma (CS) are characterized by their aggressive
      clinical behavior and poor prognosis. We evaluated the efficacy of trastuzumab
      emtansine (T-DM1), against primary HER2 positive and HER2 negative CS cell lines
      in vitro and in vivo. Eight primary CS cell lines were evaluated for HER2
      amplification and protein expression by fluorescence in situ hybridization,
      immunohistochemistry, flow cytometry and qRT-PCR. Sensitivity to T-DM1-induced
      antibody-dependent-cell-mediated-cytotoxicity (ADCC) was evaluated in 4-h
      chromium-release-assays. T-DM1 cytostatic and apoptotic activities were evaluated
      using flow cytometry based proliferation assays. In vivo activity of T-DM1 was
      also evaluated. HER2 protein overexpression and gene amplification were detected
      in 25 % (2/8) of the primary CS cell lines. T-DM1 and T were similarly effective
      in inducing strong ADCC against CS overexpressing HER2 at 3+ levels. In contrast,
      T-DM1 was dramatically more effective than T in inhibiting cell proliferation (P
      < 0.0001) and in inducing G2/M phase cell cycle arrest in the HER2 expressing
      cell lines (shift of G2/M: mean +/- SEM from 14.87 +/- 1.23 to 66.57 +/- 4.56 %,
      P < 0.0001). Importantly, T-DM1 was highly active at reducing tumor formation in
      vivo in CS xenografts overexpressing HER2 (P = 0.0001 and P < 0.0001 compared to
      T and vehicle respectively) with a significantly longer survival when compared to
      T and vehicle mice (P = 0.008 and P = 0.0001 respectively). T-DM1 may represent a
      novel treatment option for the subset of HER2 positive CS patients with disease
      refractory to chemotherapy.

PMID- 25398399
TI  - Ultrasound-guided continuous thoracic paravertebral block provides comparable
      analgesia and fewer episodes of hypotension than continuous epidural block after
      lung surgery.
AB  - PURPOSE: Both paravertebral block (PVB) and thoracic epidural block (TEB) are
      recommended for postoperative pain relief after lung surgery. The addition of
      fentanyl to the anesthetic solution became popular for TEB because of the
      stronger effects; however, there have been few comparable trials about the
      addition of fentanyl to PVB. The purpose of this study was thus to compare
      postoperative analgesia, side effects, and complications between ultrasound
      guided PVB (USG-PVB) and TEB with the addition of fentanyl to ropivacaine after
      lung surgery. METHODS: We examined 90 consecutive patients (age 18-75 years)
      scheduled for video-assisted thoracic surgery (VATS). In both groups, all blocks
      (four blocks in USG-PVB and one block in TEB) and one catheter insertion were
      performed preoperatively. Continuous postoperative infusion (0.1% ropivacaine
      plus fentanyl at 0.4 mg/day) was undertaken for 36 h in both groups. The recorded
      data included the verbal rating scale (VRS) for pain, blood pressure, side
      effects, complications for 2 days, and overall satisfaction score. RESULTS: There
      was no difference in the frequency of taking supplemental analgesics (twice or
      more frequently), or in VRS. Hypotension occurred significantly more frequently
      in TEB (n = 7/33) than in PVB (n = 1/36) (P = 0.02); on the other hand, the
      incidences of PONV and pruritus, as well as overall satisfaction score, were
      similar. There were no complications in both groups; however, the catheters
      migrated intrathoracically in four patients in PVB. CONCLUSION: USG-PVB achieved
      similar pain relief and lowered the incidence of hypotension compared with TEB.
      We conclude that both blocks with the same concentration of ropivacaine and
      fentanyl can provide adequate postoperative analgesia for VATS.

PMID- 25398401
TI  - Evidence-based Analysis on The Clinical Impact of Intraoperative Neuromonitoring
      in Thyroid Surgery: State of the Art and Future Perspectives.
AB  - Laryngeal nerve injuries are one the most critical complications during thyroid
      and parathyroid surgery. Iatrogenic damages to the recurrent laryngeal nerve
      (RLN) are relevant in terms of clinical implications, economic costs, and for
      malpractice litigation. In order to minimize potential neural damages, a
      standardized surgical technique is mandatory. Intraoperatory neuromonitoring
      (IONM) of the RLN is an important adjunct to the traditional approach and is a
      reliable tool for neural mapping and in dissection and prognostication of
      postoperative neural function 4. Because of this, most of the iatrogenic damages
      are not related to direct transection, but they are visually undetectable.
      Notwithstanding the increasing use of IONM at this stage, there is still the need
      for prospective, randomized, well-powered, and well-designed trials in order to
      further validate (via evidence-based data) the role of IONM in thyroid surgery.
      The aim of this review is to provide a critical analysis of the scientific
      evidences on the clinical impact of IONM in thyroid surgery showing the unsolved
      problems and the future challenges. 

PMID- 25398400
TI  - A short period of fasting before surgery conserves basal metabolism and
      suppresses catabolism according to indirect calorimetry performed under general
      anesthesia.
AB  - It is recommended that the period of fasting before elective surgery should be
      shortened to facilitate a rapid recovery by preventing catabolism. We examined
      the effects of a short period of fasting on metabolism by performing indirect
      calorimetry (IC) under general anesthesia. A prospective observational study
      involving 26 consecutive patients who underwent elective surgery and whose
      metabolism was evaluated using IC during anesthesia was conducted. The patients
      were divided into two groups, those who fasted for <8 h (group S) and those who
      fasted for >10 h (group L). Oxygen consumption, the volume of carbon dioxide
      emissions (VCO2), the respiratory quotient (RQ), resting energy expenditure
      (REE), and basal energy expenditure (BEE) were compared. The REE, VCO2, and RQ of
      group L (17.7 +/- 2.3 kcal/kg/day, 118.5 +/- 20.8 ml/min, and 0.71 +/- 0.12,
      respectively) were significantly lower than those of group S (19.7 +/- 2.3
      kcal/kg/day, 143.6 +/- 30.9 ml/min, and 0.81 +/- 0.09, respectively) (P < 0.05).
      In group L, the relationship between REE and BEE was weaker (r(2) = 0.501) and
      the BEE-REE slope was less steep (REE = 0.419BEE + 509.477) than those seen in
      group S (r(2) = 0.749 and REE = 1.113BEE - 376.111, respectively). Our findings
      suggest that a short period of fasting (<8 h) before surgery is more strongly
      associated with the conservation of basal metabolism.

PMID- 25398402
TI  - Image-guided thyroid nodule ablation: technical notes and critical appraisal.
AB  - Image-guided thyroid nodule ablation is a relatively new technique for the
      management of thyroid disease. Notably, if there has been the correct patient
      selection and if they are performed in high volume centers and via a standardized
      technique, image-guided thyroid nodule ablation seems to be safe and effective
      and it can be used to treat thyroid goiters. However, there is still paucity of
      level 1 evidences and recommendation comparing ablation to surgical or to other
      non-surgical treatment modalities. Herein, some technical notes for the thyroid
      nodule ablation to achieve the critical view of safety are presented. Moreover,
      an additional remark and appraisal from a surgical point of view is described. 

PMID- 25398403
TI  - Polymer cable/grip-plate system with locking screws for stable fixation to
      promote healing of trochanteric osteotomies or fractures in revision total hip
      arthroplasty.
AB  - Multiple methods have been proposed to establish stable fixation to promote
      healing of trochanteric osteotomies or fractures in revision total hip
      arthroplasty (revTHA), from wiring techniques through cable-plate systems with or
      without supplemental locking screws. The purpose of this study is to report the
      clinical results of a single cable-plate system with locked screw fixation in
      revTHA. Between 2009 and 2012, 27 grip-plates (Supercable(r) System, Kinamed
      Inc., Camarillo, CA) were used in 26 patients in 27 revTHA procedures.
      Utilization was 12 1-hole (50 mm) grip-plates, 10 2-hole (135 mm) grip-plates,
      four 4-hole (190 mm) grip-plates, and one 6-hole (245 mm) grip-plate. There were
      14 women and 12 men. Age averaged 63.2 years and BMI averaged 29.4 kg/m2. At
      average 2.5 year follow-up, grip-plate fixation was considered successful in 22
      hips (81%) with five failures. Three failures consisted of 50 mm/short grip
      plates used in one trochanteric slide, and two intraoperative trochanteric
      fractures during revTHA. The two additional failures were related to pre-revision
      trochanteric avulsion from bony necrosis of the proximal femur. An additional
      three grip-plates were removed electively for soft-tissue irritation and pain but
      with successful fixation and bony healing. Thus 70% of hips were free of
      reoperation related to the grip-plate. All other hips had successful fixation and
      the grip-plate was not symptomatic. In this study, the cable-grip system and
      isoelastic Supercables provided reliable fixation for adequate healing of
      difficult ETO and trochanteric fractures with an 81% rate of mechanical success
      with radiographic and clinical healing observed. 

PMID- 25398404
TI  - Gap junction remodelling by chronic pressure overload is related to the increased
      susceptibility to atrial fibrillation in rat heart.
AB  - AIMS: Left atrial (LA) fibrosis caused by various pathological stimuli is a
      common finding. However, the difference of atrial remodelling via haemodynamic
      change in diverse cardiomyopathy has not been elucidated. METHODS AND RESULTS:
      Male Sprague-Dawley rats (6-8 weeks, n = 180) were randomly assigned to three
      groups and corresponding sham control groups: (i) ischaemic cardiomyopathy, (ii)
      left ventricular hypertrophy (LVH), and (iii) dilated cardiomyopathy. At 12 weeks
      after operation, atrial fibrillation (AF) inducibility and duration were assessed
      by in vivo burst transoesophageal pacing. Using the Langendorff apparatus, left
      ventricular (LV) function and pressure were measured. The expression of connexin
      43 (Cx43) and alpha-smooth muscle actin (alpha-SMA) in atrial tissues was
      assessed by quantitative real-time polymerase chain reaction and
      immunohistochemical staining. Fibrosis was analysed by Masson's trichrome
      staining. Compared with controls, the LA weight/heart weight ratio was increased
      in the LVH group alone, and was significantly correlated with AF duration (P <
      0.001, R = 0.388). Atrial fibrillation inducibility and duration were higher and
      longer only in the LVH group (P = 0.002, 0.079, respectively), and isolated LV
      diastolic dysfunction and elevated LV pressure were observed. Although alpha-SMA
      expression and fibrosis were increased in all three cardiomyopathy models, down
      regulation of Cx43 expression in the LA was observed in the LVH group alone.
      CONCLUSION: Chronic pressure overload in the absence of LV systolic dysfunction
      resulted in LA hypertrophy and increased susceptibility to AF, which might be
      related to conduction abnormality via decreased expression and lateral
      distribution of Cx43 as well as interstitial fibrosis.

PMID- 25398405
TI  - Cardiac resynchronization therapy reduces T-wave alternans in patients with heart
      failure.
AB  - AIMS: T-wave alternans (TWA) represents myocardial instability. The present study
      was to determine the impact of cardiac resynchronization therapy (CRT) on TWA and
      left ventricular ejection fraction (LVEF) in heart failure patients. METHODS AND
      RESULTS: T-wave alternans was analysed using a spectral method in 27 CRT-ICD
      patients. Ambulatory device electrograms were collected and LVEF and New York
      Heart Association (NYHA) classification were assessed at baseline prior to CRT
      and 3 months following CRT. Patients were followed for 6 months to monitor
      cardiac events. Spectral TWA of device electrograms was measured during AAI and
      CRT pacing tests. Each pacing mode had the up-titration pacing rate from 90 to
      105 b.p.m. with 90 s for each pacing rate. At baseline, 20 (76.9%) patients had
      TWA during AAI pacing tests and 13 (50%) during CRT pacing tests (P = 0.044
      between two pacing modes). Following 3-month CRT, TWA was identified in 11
      patients (45.8%) during AAI pacing tests (a 31.1% reduction from the baseline
      value, P = 0.023) and 7 patients (28%) during CRT pacing tests (a 22% reduction,
      P = 0.108). Six of seven patients who had cardiac events had TWA (three patients
      had arrhythmic events, two died of heart failure, one received heart transplant).
      Overall, LVEF improved from 27.3 +/- 5.8 to 35.9 +/- 10.5% (P < 0.001) and NYHA
      classification improved from 2.8 +/- 0.6 to 1.6 +/- 0.6 after 3-month CRT (P <
      0.001). CONCLUSION: In heart failure patients who receive a CRT-ICD, CRT reduces
      TWA that is associated to cardiac events, suggesting that CRT promotes clinically
      significant reverse electrical and mechanical remodelling.

PMID- 25398406
TI  - Working mothers of the World Health Organization Western Pacific offices: lessons
      and experiences to protect, promote, and support breastfeeding.
AB  - Optimal breastfeeding saves lives. However, suboptimal breastfeeding is
      prevalent, primarily resulting from inappropriate promotion of infant formula and
      challenges of working mothers to continue breastfeeding. The article aims to
      determine the extent to which World Health Organization (WHO) policies protect,
      promote, and support breastfeeding women working at the WHO, Western Pacific
      Region. An online survey targeted all female WHO and contractual staff in all
      country and regional offices, who delivered a baby between July 24, 2008 and July
      24, 2013. Respondents advised on how the worksite could better support
      breastfeeding. Thirty-two female staff from 11 of the 12 WHO offices within the
      Western Pacific Region responded. "Returning to work" (44%) and "not having
      enough milk" (17%) were the most commonly reported reasons for not breastfeeding.
      Eighteen (56%) reported using infant formula and 8 (44%) reported that the
      product was prescribed. Among the suggestions given to better support
      breastfeeding, 10 (32%) recommended having a private room with a chair, table,
      electric outlet, and refrigerator. The findings show that women working at the
      WHO face similar challenges to mothers outside the WHO. Based on the findings, we
      recommend the following: (1) provide prenatal/postpartum breastfeeding counseling
      services for employees; (2) establish breastfeeding rooms in country offices and
      regularly orient staff on agency policies to protect, promote, and support
      breastfeeding; (3) annually celebrate World Breastfeeding Week with employees;
      (4) encourage other public and private institutions to conduct online surveys and
      elicit recommendations from mothers on how their workplace can support
      breastfeeding; and (5) conduct a larger survey among UN agencies on how to better
      protect, promote, and support breastfeeding. 

PMID- 25398408
TI  - Researcher who had job offer withdrawn sues anonymous commentator for defamation.

PMID- 25398407
TI  - Impact of body mass index on surgical outcomes after esophagectomy for patients
      with esophageal squamous cell carcinoma.
AB  - BACKGROUND: Patients with overweight reportedly have more comorbidities,
      including diabetes mellitus and cardiovascular disease, and longer operating
      times as well as more blood loss during surgery compared with those with normal
      weight. However, the impact of overweight on the short-term outcome after
      transthoracic esophagectomy for patients with esophageal squamous cell carcinoma
      (ESCC) remains unclear. We hypothesized that overweight has a negative impact on
      short-term surgical outcomes after esophagectomy for patients with ESCC. METHODS:
      A total of 304 patients who underwent transthoracic esophagectomy for ESCC were
      included in this study. Body mass index (BMI) was classified into three
      categories, <18.49, 18.50-24.99, and >25.00 (kg/m(2)), defined as low, normal,
      and high BMI, respectively, according to the World Health Organization criteria.
      We investigated the association of BMI status with patient demographics and
      surgical outcomes after esophagectomy for patients with ESCC. In addition,
      overall survival and relapse-free survival stratified by BMI were compared.
      RESULTS: Fifty-nine (19.4 %) and 41 (13.4 %) patients were classified to low BMI
      and high BMI, respectively. The high-BMI group had significantly higher
      comorbidity rates of diabetes mellitus (p < 0.01) and anastomotic leakage (p =
      0.011) than the normal-BMI group. There were no significant association between
      high BMI and another various complications except for an anastomotic leakage,
      severe complications defined by Clavien-Dindo classification and in-hospital
      mortality. In multivariate analysis, high BMI was a significant risk factor for
      anastomotic leakage (p = 0.030, hazard ratio; 3.423, 95%CI; 1.128-10.38). On the
      other hand, no significant association was observed between low BMI and short
      surgical outcomes. There were no significant differences in overall and relapse
      free survival among the three BMI groups in univariate and multivariate analysis
      (p = 0.128 and p = 0.584, respectively). CONCLUSION: The surgical treatment
      should not be denied for patients with ESCC due to overweight and underweight.
      However, intraoperative prevention and postoperative careful monitoring for
      anastomotic leakage might be required after esophagectomy for overweight patients
      with ESCC.

PMID- 25398409
TI  - Sterilization-Induced Changes in Surface Topography of Biodegradable POSS-PCLU
      and the Cellular Response of Human Dermal Fibroblasts.
AB  - The field of tissue engineering is rapidly evolving, generating numerous
      biodegradable materials suited as regeneration platforms. Material sterility is
      of fundamental importance for clinical translation; however, a few studies have
      systematically researched the effects of different sterilization methods on
      biodegradable materials. Here, we exposed a novel bioabsorbable nanocomposite
      based on a poly(E-caprolactone urea) urethane backbone integrating polyhedral
      oligomeric silsesquioxane nanoparticles (POSS-PCLU) to autoclave, microwave,
      antibiotics, and 70% ethanol sterilization and systematically correlated
      differences in material characteristics to the attachment, viability,
      proliferative capacity, and shape of human dermal fibroblasts (HDFa).
      Nanotopographical profiling of autoclaved or microwaved surfaces revealed
      relatively deep nano-grooves, increasing total surface area, roughness, and
      hydrophobicity, which resulted in significantly fewer adherent cells. Antibiotics
      or 70% ethanol-treated surfaces displayed shallower nano-grooves, a more
      hydrophilic character, and significantly greater cellular adhesion (p<0.05). In
      fact, relative cell proliferation on ethanol-treated films surpassed that of
      cells grown on every other surface by a factor of 9 over 7 days. Filamentous
      actin staining demonstrated spindle-like morphologies characteristic of HDFa when
      grown on ethanol-treated films as opposed to cells grown on other films that were
      significantly more spread out (p<0.05). We argue that treatment with 70% ethanol
      serves not only as a laboratory-based sterilizing agent but also as a
      postproduction processing tool to enhance cytocompatibility of tissue engineering
      scaffolds. 

PMID- 25398410
TI  - Carbon dioxide capture utilizing zeolites synthesized with paper sludge and scrap
      glass.
AB  - The present work introduces the study of the CO2 capture process by zeolites
      synthesized from paper sludge and scrap glass. Zeolites ZSM-5, analcime and
      wairakite were produced by means of two types of Structure Directing Agents
      (SDA): tetrapropilamonium (TPA) and ethanol. On the one hand, zeolite ZSM-5 was
      synthesized using TPA; on the other hand, analcime and wairakite were produced
      with ethanol. The temperature programmed desorption (TPD) technique was performed
      for determining the CO2 sorption capacity of these zeolites at two sorption
      temperatures: 50 and 100  degrees C. CO2 sorption capacity of zeolite ZSM-5
      synthesized at 50  degrees C was 0.683 mmol/g representing 38.2% of the value
      measured for a zeolite ZSM-5 commercial. Zeolite analcime showed a higher CO2
      sorption capacity (1.698 mmol/g) at 50  degrees C and its regeneration
      temperature was relatively low. Zeolites synthesized in this study can be used in
      the purification of biogas and this will produce energy without increasing the
      atmospheric CO2 concentrations.

PMID- 25398411
TI  - Effect of microwave pre-treatment of thickened waste activated sludge on biogas
      production from co-digestion of organic fraction of municipal solid waste,
      thickened waste activated sludge and municipal sludge.
AB  - Anaerobic co-digestion of organic fraction of municipal solid waste, with
      thickened waste activated sludge and primary sludge has the potential to enhance
      biodegradation of solid waste, increase longevity of existing landfills and lead
      to more sustainable development by improving waste to energy production. This
      study reports on mesophilic batch and continuous studies using different
      concentrations and combinations (ratios) of organic fraction of municipal solid
      waste, thickened waste activated sludge (microwave pre-treated and untreated) and
      primary sludge to assess the potential for improved biodegradability and specific
      biogas production. Improvements in specific biogas production for batch assays,
      with concomitant improvements in total chemical oxygen demand and volatile solid
      removal, were obtained with organic fraction of municipal solid waste:thickened
      waste activated sludge:primary sludge mixtures at a ratio of 50:25:25 (with and
      without thickened waste activated sludge microwave pre-treatment). This
      combination was used for continuous digester studies. At 15 d hydraulic retention
      times, the co-digestion of organic fraction of municipal solid waste:organic
      fraction of municipal solid waste:primary sludge and organic fraction of
      municipal solid waste:thickened waste activated sludge microwave:primary sludge
      resulted in a 1.38- and 1.46-fold increase in biogas production and concomitant
      waste stabilisation when compared with thickened waste activated sludge:primary
      sludge (50:50) and thickened waste activated sludge microwave:primary sludge
      (50:50) digestion at the same hydraulic retention times and volumetric volatile
      solid loading rate, respectively. The digestion of organic fraction of municipal
      solid waste with primary sludge and thickened waste activated sludge provides
      beneficial effects that could be implemented at municipal wastewater treatment
      plants that are operating at loading rates of less than design capacity.

PMID- 25398412
TI  - Mold contamination in a controlled hospital environment: a 3-year surveillance in
      southern Italy.
AB  - BACKGROUND: Environmental monitoring of airborne filamentous fungi is necessary
      to reduce fungal concentrations in operating theaters and in controlled
      environments, and to prevent infections. The present study reports results of a
      surveillance of filamentous fungi carried out on samples from air and surfaces in
      operating theaters and controlled environments in an Italian university hospital.
      METHODS: Sampling was performed between January 2010 and December 2012 in 32
      operating theaters and five departments with high-risk patients. Indoor air
      specimens were sampled using a microbiological air sampler; Rodac contact plates
      were used for surface sampling. Fungal isolates were identified at the level of
      genera and species. RESULTS: Sixty-one samples (61/465; 13.1%) were positive for
      molds, with 18 from controlled environments (18/81; 22.2%) and 43 (43/384; 11.2%)
      from operating theaters. The highest air fungal load (AFL, colony-forming units
      per cubic meter [CFU/m(3)]) was recorded in the ophthalmology operating theater,
      while the pediatric onco-hematology ward had the highest AFL among the wards (47
      CFU/m(3)). The most common fungi identified from culture of air specimens were
      Aspergillus spp. (91.8%), Penicillium spp., (6%) and Paecilomyces spp. (1.5%).
      During the study period, a statistically significant increase in CFU over time
      was recorded in air-controlled environments (p = 0.043), while the increase in
      AFL in operating theaters was not statistically significant (p = 0.145). Molds
      were found in 29.1% of samples obtained from surfaces. Aspergillus fumigatus was
      the most commonly isolated (68.5%). CONCLUSIONS: Our findings will form the basis
      for action aimed at improving the air and surface quality of these special wards.
      The lack of any genetic analysis prevented any correlation of fungal
      environmental contamination with onset of fungal infection, an analysis that will
      be undertaken in a prospective study in patients admitted to the same hospital.

PMID- 25398413
TI  - Who knows the risk? A multilevel study of systematic variations in work-related
      safety knowledge in the European workforce.
AB  - OBJECTIVES: Health and safety instructions are important components of
      occupational prevention. Albeit instruction is mandatory in most countries,
      research suggests that safety knowledge varies among the workforce. We analysed a
      large European sample to explore if all subgroups of employees are equally
      reached. In a comparative perspective, we also investigated if country-level
      determinants influence the variance of safety knowledge between countries.
      METHODS: We used data on 24,534 employees from 27 countries who participated in
      the 2010 European Working Conditions Survey. Safety knowledge was measured as
      self-assessed quality of safety information. Country-level determinants were
      added from Eurostat databases (gross domestic product) and the European Survey of
      Enterprises on New and Emerging Risks (ESENER) study (% companies with A: safety
      plan or B: a labour inspectorate visit). Associations between knowledge,
      sociodemographic, occupational characteristics and macrodeterminants were studied
      with hierarchical regression models. RESULTS: In our sample, 10.1% reported a low
      degree of health and safety knowledge. Across all countries, younger workers,
      lower educated workers, production workers, private sector employees, those with
      less job experience or a temporary contract, or those who work in small
      businesses were more likely to report low levels of information. Moreover, low
      information prevalence varied by country. Countries with a high proportion of
      companies with a safety plan and recent labour inspectorate on-site visits had
      higher proportions of informed workers. CONCLUSIONS: A vast majority reported to
      be well informed about safety risks but systematic inequalities in the degree of
      knowledge between subgroups were evident. Further efforts on the workplace, the
      organisational and the political level are needed to universally implement
      existing occupational safety regulations.

PMID- 25398414
TI  - Common mental disorders and cause-specific disability retirement.
AB  - OBJECTIVES: Common mental disorders are prevalent among employees and may cause
      work disability. We aimed to examine the association between common mental
      disorders and disability retirement, with an emphasis on the severity of
      disorders and diagnostic causes for retirement. METHODS: Our data were derived
      from the Helsinki Health Study cohort on the staff of the City of Helsinki,
      Finland. The baseline mail surveys were made in 2000-2002 among employees
      reaching ages 40, 45, 50, 55 and 60 in each year (n=8960, response rate 67%, 80%
      women). Disability retirement events from national registers (n=628) were
      followed up by the end of 2010 and linked to the baseline data. After exclusions,
      the number of participants was 6525. Common mental disorders were measured by the
      General Health Questionnaire 12-item version (GHQ-12). Covariates at baseline
      included sociodemographic, work-related and health-related factors. Hazard ratios
      (HR) and 95% CIs were calculated using Cox proportional hazards models. RESULTS:
      Common mental disorders showed a graded association with disability retirement.
      For disability retirement due to any diagnostic cause, the fully adjusted HR for
      the GHQ-12 score 7-12 was 2.16, 95% CI 1.63 to 2.85. For disability retirement
      due to mental disorders the corresponding HR was 7.46, 95% CI 4.46 to 12.49. For
      disability retirement due to musculoskeletal diseases, the association was weaker
      and did not survive all adjustments. CONCLUSIONS: Common mental disorders are an
      important antecedent of disability retirement in general and due to mental
      disorders in particular. Successful measures against common mental disorders may
      prevent disability retirement due to mental disorders.

PMID- 25398415
TI  - Occupational polycyclic aromatic hydrocarbon exposure and risk of larynx cancer:
      a systematic review and meta-analysis.
AB  - Polycyclic aromatic hydrocarbons (PAH) are genotoxic substances formed during
      combustion. Occupational PAH exposure has been shown to increase the risk of lung
      cancer and may be associated with other respiratory cancers. We conducted a
      systematic review and meta-analysis to clarify the relationship between
      occupational PAH exposures and larynx malignancies. We searched EMBASE and
      MEDLINE (until July 2014) using a series of search strings developed to seek case
      control studies or longitudinal studies of workers (Population) exposed to PAHs
      (Exposure) and their risk for larynx cancer incidence and/or mortality (Outcome).
      Two independent reviewers screened the titles and abstracts for eligible articles
      and a third reviewer negotiated consensus. Further assessments of eligibility and
      sources of bias were conducted in a similar manner. The study results were pooled
      with random effects meta-analysis. The search resulted in 3377 records. The data
      of 92 full-text articles representing 63 studies were included and extracted. The
      majority of studies (n=47) was judged likely to be biased; only 16 studies were
      judged as methodologically adequate. The pooled effect size was 1.45 (95% CI 1.30
      to 1.62; I(2)=30.7%; [Formula: see text]=0.03) for larynx cancer incidence and
      1.34 (95% CI 1.18 to 1.53; I(2)=23.8%; [Formula: see text]=0.03) for larynx
      cancer mortality. While few studies allowed an investigation of dose-response,
      these indicate a positive dose-response effect. Although most studies may
      underestimate the true effect due to inexact approximations of PAH exposure, the
      meta-analysis suggests a robust positive association between PAH and larynx
      cancer. 

PMID- 25398416
TI  - An Overview of Testosterone Therapy.
AB  - Millions of men, as a result of the natural aging process, injury, illness, and
      medical therapies, experience a decline in testosterone levels that necessitate a
      need for testosterone supplementation therapy (TST). The signs and symptoms of
      testosterone decline may occur gradually, and low testosterone levels may be
      misdiagnosed as other medical conditions. Over the past two decades, there has
      been an increase in testing of testosterone levels and the use of TST. With so
      many men now on TST, it is essential for health care professionals to know the
      signs and symptoms, the causes of testosterone decline, how testosterone
      deficiency is diagnosed, what pathological changes are associated with
      testosterone decline, and the benefits and risks of TST. In addition, health care
      providers need to be aware of the various forms of testosterone available as well
      as the advantages and disadvantages of each. This article provides a brief
      overview of testosterone deficiency, TST treatment options and guidelines, and
      the risks and benefits associated with of TST. 

PMID- 25398417
TI  - HIV and STI prevalence and injection behaviors among people who inject drugs in
      Nairobi: results from a 2011 bio-behavioral study using respondent-driven
      sampling.
AB  - There is a dearth of evidence on injection drug use and associated HIV infections
      in Kenya. To generate population-based estimates of characteristics and HIV/STI
      prevalence among people who inject drugs (PWID) in Nairobi, a cross-sectional
      study was conducted with 269 PWID using respondent-driven sampling. PWID were
      predominantly male (92.5 %). An estimated 67.3 % engaged in at least one risky
      injection practice in a typical month. HIV prevalence was 18.7 % (95 % CI 12.3
      26.7), while STI prevalence was lower [syphilis: 1.7 % (95 % CI 0.2-6.0);
      gonorrhea: 1.5 % (95 % CI 0.1-4.9); and Chlamydia: 4.2 % (95 % CI 1.2-7.8)]. HIV
      infection was associated with being female (aOR, 3.5; p = 0.048), having first
      injected drugs 5 or more years ago (aOR, 4.3; p = 0.002), and ever having
      practiced receptive syringe sharing (aOR, 6.2; p = 0.001). Comprehensive harm
      reduction programs tailored toward PWID and their sex partners must be fully
      implemented as part of Kenya's national HIV prevention strategy.

PMID- 25398418
TI  - HIV prevalence and risk behaviors among Mozambicans working in South African
      mines.
AB  - Mineworkers are considered a population at risk for HIV due to risk behaviors
      associated with migratory work patterns. This was the first study in Mozambique
      to determine the prevalence of HIV and associated demographic and risk behaviors,
      and assess use and access to prevention and healthcare services among Mozambicans
      working in South African mines. Men who had worked in a South African mine in the
      past 12 months were recruited between February and May 2012 using time location
      sampling (TLS) at the Ressano Garcia border between Mozambique and South Africa.
      Demographic and behavioral data were collected through a standardized
      questionnaire, and HIV prevalence was estimated by testing dried blood spots
      (DBS) with two enzyme immunoassays. In total, 432 eligible mine workers were
      recruited. Mean age was 43 years. Most were married or cohabitating; among them,
      12.6 % had two or more wives/marital partners in Mozambique. In the 12 months
      preceding the survey, 24.7 % had an occasional sexual partner, and 6.6 % had at
      least one partner who was a female sex worker. Only one in five (18.5 %) used a
      condom during last sex. HIV prevalence among mineworkers was 22.3 %, and 74.6 %
      of those who tested positive as part of the survey did not know their status. HIV
      prevalence was significantly higher (p = 0.018) among those that were
      uncircumcised (31.2 %) than those who were circumcised (18.5 %). Multiple
      partners (multiple spouses, cross-border relations, and multiple occasional
      partnerships), inconsistent condom use, and a high proportion of infected
      mineworkers who do not know their HIV status increases the risk of HIV
      transmission in this population. Combination strategies involving the promotion
      of condom use, HIV testing, and male circumcision should be strengthened among
      mineworkers.

PMID- 25398419
TI  - Rapid follow-up for patients after psychiatric crisis.
AB  - Patients in psychiatric crisis often lack connection to community resources and
      present to emergency departments (EDs) for care. A transitional psychiatry clinic
      (TPC) bridged patients after ED visit. These retrospective chart review data of
      390 patients were analyzed by ANOVA, logistic regression and survival analysis.
      Predictors of ED return included psychosis, personality disorder and increased
      number of prior ED visits. Longer wait for the TPC was associated strongly with
      non-attendance. TPC appointment within 3 days was associated with significantly
      longer time in the community without ED presentation. Rapid follow-up after ED
      visits increased attendance at aftercare and lengthens community tenure. 

PMID- 25398420
TI  - Clinicopathological heterogeneity in ovarian clear cell adenocarcinoma: a study
      on individual therapy practice.
AB  - Ovarian clear cell adenocarcinoma (CCA) has been believed to be a lethal
      histological subtype of an epithelial ovarian adenocarcinoma (EOA); its precursor
      has been assumed to be endometriosis. However, it has been reported that CCAs
      occasionally exhibit different clinical behaviors, suggesting that CCAs might not
      belong to a single category. We focused on CCAs combined with other histological
      types of EOAs; we re-evaluated the pathology of 46 CCAs and divided them into two
      subgroups: 35 CCAs alone (pure-type CCAs); and 11 CCAs with other histological
      types, endometrioid adenocarcinomas (EAs) or/and serous adenocarcinomas (SAs)
      (mixed-type CCAs). Immunohistochemical analysis for expression of ARID1A, p53,
      PTEN, Annexin 4, hepatocyte nuclear factor-1beta (HNF-1beta), and WT-1 was
      employed. We identified that patients with endometriosis were younger than those
      without endometriosis in pure-type CCAs (P < 0.005). In mixed-type CCAs, the
      immunohistochemical-staining patterns revealed internal transition of each
      histological component. In pure-type CCAs, expressions of ARID1A and p53 were
      mutually altered, and altered expression of p53 was associated with worse
      prognosis than that of ARID1A (P < 0.001). Our results provide evidence that CCAs
      would have clinicopathological heterogeneity, determining the patient's
      prognosis. Furthermore, immunohistochemical analysis may shed light on the
      selection of appropriate treatment, including chemotherapy.

PMID- 25398421
TI  - 68Ga-NOTA-exendin-4 PET/CT in detection of occult insulinoma and evaluation of
      physiological uptake.

PMID- 25398422
TI  - [Seeing more : Technical innovations in regional anesthesia].
AB  - Visualization and verification are key factors since the implementation of
      ultrasound-guided regional anesthesia. This article reviews and discusses newer
      technical innovations in regional anesthesia with regard to optimization of
      needle guidance, improvements in needle visibility, technical improvements in
      ultrasound techniques and innovative technologies in regional anesthesia.
      Clinically available applications are presented as well as experimental tools and
      techniques with a potential for clinical implementation in the future. Mechanical
      needle guides are used to improve alignment of needle axis and ultrasound beam
      axis. Compound imaging technology improves needle visibility in steep needle
      insertion angles and is already implemented in daily clinical practice.
      Sonoelastography improves tissue discrimination and detection of small amounts of
      fluids. Benefits of 3D and 4D ultrasound in regional anesthesia are discussed as
      well as experimental tools for tissue discrimination, such as optical reflection
      spectrophotometry. 

PMID- 25398423
TI  - Advances in the stroke system of care.
AB  - OPINION STATEMENT: The stroke system of care is undergoing significant evolution.
      There are promising data to suggest that with new technologies and approaches,
      primary prevention and community education will become easier and more
      accessible, and will allow people to have greater participation in their own
      healthcare. The evidence-based primary and comprehensive stroke center concepts
      have been translated into robust, rapidly growing certification programs. The
      continued dissemination of improved EMS routing protocols allows for better
      allocation of patients to stroke centers, even as we confront the challenge of
      further improving prehospital recognition of stroke. National quality improvement
      initiatives help to ensure that patients directed to stroke centers receive
      evidence-based treatment, which has resulted in improved stroke care and better
      clinical outcomes. In remote areas, the use of technologies such as telemedicine
      to extend the reach of vascular neurologists has resulted in increased
      administration of time-sensitive thrombolytic therapy and better patient
      outcomes, although greater efficiency within the stroke system will likely be
      needed to realize the potential benefits of endovascular therapy. System-level
      paradigms for aggressive medical management promise to lessen the burden of
      recurrent stroke. Finally, further integration of rehabilitation programs into
      stroke centers and coordination with community-based rehabilitation services is
      needed to ensure the best possible outcome for stroke patients.

PMID- 25398425
TI  - Etiologic stroke subtypes: updated definition and efficient workup strategies.
AB  - OPINION STATEMENT: Stroke affects approximately 16.9 million individuals per year
      worldwide and is the second leading cause of death. Stroke represents a family of
      related, but distinct subtypes. Classifying stroke subtypes must take into
      account various aspects of a standardized stroke workup to allow optimization of
      treatment and prevention strategies. Secondary prevention and pharmacologic
      treatment is tailored based on stroke mechanism. Additionally prognostication and
      recurrent risk also depends on stroke etiology. Efficient workup of stroke relies
      on a thorough history, clinical examination, imaging studies, and putative
      mechanism of stroke that lead the treating physician to a particular etiological
      path. Here , we provide the reader with updated definitions of etiologic ischemic
      stroke types as well as efficient workup strategies.

PMID- 25398424
TI  - Strategies for early stroke recovery: what lies ahead?
AB  - OPINION STATEMENT: Most patients experience some degree of recovery after a
      stroke, but the majority of patients still have persistent impairments months
      later. Most recovery occurs early after a stroke, in the first few weeks to
      months, corresponding to a period of enhanced neuroplasticity. We are beginning
      to understand the mechanisms that underlie this recovery process, and how we can
      take advantage of this plasticity in designing rehabilitative interventions. In
      this review, we focus on recent behavioral, pharmacological, and brain
      stimulation strategies that have shown promise in augmenting stroke recovery.
      Several studies, both in animals and humans, suggest that early initiation and
      high doses of therapy are crucial for maximizing the benefits of rehabilitation.
      The investigation of early and intensive therapy in clinical trials has been
      limited, likely due to the logistical challenges of conducting such studies.
      Other strategies for promoting recovery seek to modulate neuroplasticity or to
      enhance the effects of rehabilitation, including the use of pharmacological
      agents, stem cell therapy and non-invasive brain stimulation. While there has
      been recent growth in stroke recovery and rehabilitation research, there is still
      a great need for more basic science and clinical research to further our
      understanding of the stroke recovery process and develop optimal rehabilitative
      strategies for promoting stroke recovery.

PMID- 25398426
TI  - Controversies in cardioembolic stroke.
AB  - OPINION STATEMENT: Cardioembolic (CE) stroke mechanisms account for a significant
      number of ischemic strokes; however, the true burden is likely underestimated. It
      is critically important to identify patients with CE strokes because these
      individuals have high recurrence rates and represent a subgroup of patients who
      may benefit from targeted therapy in the form of anticoagulation or device based
      treatments. Current guidelines offer recommendations for diagnosis and treatment
      of these patients; however, important questions remain. First, appropriate
      cardiac testing in the setting of CE must be individualized and the optimal
      duration of electrocardiographic monitoring to rule out atrial fibrillation (AF)
      is unclear. Second, risk stratification tools for AF remain understudied, and
      there is controversy about which anticoagulant agents are most appropriate.
      Lastly, important potential CE sources of stroke such as patent foramen ovale
      have garnered significant attention recently, and debate regarding how to manage
      these patients persists. In this review, we discuss some of the important
      controversies in diagnosing and treating patients with possible CE stroke,
      pointing to areas where future research might be particularly valuable.

PMID- 25398427
TI  - Physicochemical and formulation developability assessment for therapeutic peptide
      delivery--a primer.
AB  - Peptides are an important class of endogenous ligands that regulate key
      biological cascades. As such, peptides represent a promising therapeutic class
      with the potential to alleviate many severe disease states. Despite their
      therapeutic potential, peptides frequently pose drug delivery challenges to
      scientists. This review introduces the physicochemical, biophysical,
      biopharmaceutical, and formulation developability aspects of peptides pertinent
      to the drug discovery-to-development interface. It introduces the relevance of
      these properties with respect to the delivery modalities available for peptide
      pharmaceuticals, with the parenteral route being the most prevalent route of
      administration. This review also presents characterization strategies for oral
      delivery of peptides with the aim of illuminating developability issues with the
      drug candidate. A brief overview of other routes of administration, including
      inhaled, transdermal, and intranasal routes, is provided as these routes are
      generally preferred by patients over injectables. Finally, this review presents
      formulation techniques to mitigate some of the developability obstacles
      associated with peptide delivery. The authors emphasize opportunities for the
      thoughtful application of pharmaceutical science to the development of peptide
      drugs and to the general advancement of this promising class of pharmaceuticals. 

PMID- 25398428
TI  - Rethinking capacity building for knowledge mobilisation: developing multilevel
      capabilities in healthcare organisations.
AB  - BACKGROUND: Knowledge mobilisation in healthcare organisations is often carried
      out through relatively short-term projects dependent on limited funding, which
      raises concerns about the long-term sustainability of implementation and
      improvement. It is becoming increasingly recognised that the translation of
      research evidence into practice has to be supported by developing the internal
      capacity of healthcare organisations to engage with and apply research. This
      process can be supported by external knowledge mobilisation initiatives
      represented, for instance, by professional associations, collaborative research
      partnerships and implementation networks. This conceptual paper uses empirical
      and theoretical literature on organisational learning and dynamic capabilities to
      enhance our understanding of intentional capacity building for knowledge
      mobilisation in healthcare organisations. DISCUSSION: The discussion is
      structured around the following three themes: (1) defining and classifying
      capacity building for knowledge mobilisation; (2) mechanisms of capability
      development in organisational context; and (3) individual, group and
      organisational levels of capability development. Capacity building is presented
      as a practice-based process of developing multiple skills, or capabilities,
      belonging to different knowledge domains and levels of complexity. It requires an
      integration of acquisitive learning, through which healthcare organisations
      acquire knowledge and skills from knowledge mobilisation experts, and experience
      based learning, through which healthcare organisations adapt, absorb and modify
      their knowledge and capabilities through repeated practice. Although the starting
      point for capability development may be individual-, team- or organisation
      centred, facilitation of the transitions between individual, group and
      organisational levels of learning within healthcare organisations will be needed.
      Any initiative designed to build capacity for knowledge mobilisation should
      consider the subsequent trajectory of newly developed knowledge and skills within
      the recipient healthcare organisations. The analysis leads to four principles
      underpinning a practice-based approach to developing multilevel knowledge
      mobilisation capabilities: (1) moving from 'building' capacity from scratch
      towards 'developing' capacity of healthcare organisations; (2) moving from
      passive involvement in formal education and training towards active, continuous
      participation in knowledge mobilisation practices; (3) moving from lower-order,
      project-specific capabilities towards higher-order, generic capabilities allowing
      healthcare organisations to adapt to change, absorb new knowledge and innovate;
      and (4) moving from single-level to multilevel capability development involving
      transitions between individual, group and organisational learning.

PMID- 25398429
TI  - Hypoxia induces stem and leaf nitric oxide (NO) emission from poplar seedlings.
AB  - MAIN CONCLUSION: Hypoxia leads to NO formation in poplar roots. Additionally,
      either NO or a NO derivative is transported from the roots to the shoot causing
      NO emission from aboveground plant organs. Nitric oxide (NO) is involved in the
      response of plants to various forms of stress including hypoxia. It also seems to
      play an important role in stomatal closure during stress exposure. In this study,
      we investigated the formation of NO in roots of intact poplar (Populus *
      canescens) plants in response to hypoxia, as well as its dependence on nitrate
      availability. We further addressed the question if root hypoxia triggers NO
      emission from aboveground plant parts, i.e., stems and leaves of young poplar
      trees. Our results indicate that NO is formed in poplar roots in response to
      hypoxia and that this production depends on the availability of nitrate and its
      conversion product nitrite. As long as nitrate was available in the nutrient
      solution, NO emission of roots occurred; in the range of the nitrate
      concentrations (10-100 uM) tested, NO emission was widely independent on nitrate
      concentration. However, the time period in which NO was emitted and the total
      amount of NO emitted strongly depended on the nitrate concentration of the
      solution. Hypoxia also led to increased NO emissions from the leaves and stems of
      the trees. There was a tight correlation between leaf and stem NO emission of
      hypoxia-treated plants. We propose that NO is produced by nitrate reductase in
      the roots and either NO itself, a metabolic NO precursor, or a NO derivative is
      transported in the xylem sap of the trees from the roots to the shoot thereby
      mediating NO emission from aboveground parts of the plant.

PMID- 25398430
TI  - iPad use in Iowa Research Network family physician offices.
AB  - BACKGROUND: Through a cancer research infrastructure building grant, iPads were
      given to health care providers in family physician offices. The purpose of this
      study was to determine the use and application of iPads in the Iowa Research
      Network. METHODS: A Qualtrics survey was sent to 81 iPad recipients after
      institutional review board approval. RESULTS: Fifty-nine percent responded and
      85% reported they have used the iPad. The main reason for use of the iPad was
      browsing the World Wide Web for health care information. Open-ended comments
      supported use of the iPad for photographic documentation of wound and other skin
      lesions for insertion into the medical record and it helped improve clinic flow
      by making it easier to put orders in the system through the iPad. CONCLUSIONS:
      Tablet uses are variable in physician offices with provider's gathering health
      care information from the Internet and securing education material for patients
      as the frequent usages.

PMID- 25398431
TI  - Defects in cortical microarchitecture among African-American women with type 2
      diabetes.
AB  - SUMMARY: Patients with type 2 diabetes mellitus (DM2) have increased fracture
      risk. We found that African-American women with DM2 have increased cortical
      porosity and lower cortical bone density at the radius than non-diabetic
      controls. These cortical deficits are associated with hyperglycemia and may
      contribute to skeletal fragility associated with DM2. INTRODUCTION: Fracture risk
      is increased in patients with type 2 diabetes mellitus (DM2) despite normal areal
      bone mineral density (aBMD). DM2 is more common in African-Americans than in
      Caucasians. It is not known whether African-American women with DM2 have deficits
      in bone microstructure. METHODS: We measured aBMD at the spine and hip by DXA,
      and volumetric BMD (vBMD) and microarchitecture at the distal radius and tibia by
      HR-pQCT in 22 DM2 and 78 non-diabetic African-American women participating in the
      Study of Women Across the Nation (SWAN). We also measured fasting glucose and
      HOMA-IR. RESULTS: Age, weight, and aBMD at all sites were similar in both groups.
      At the radius, cortical porosity was 26% greater, while cortical vBMD and tissue
      mineral density were lower in women with DM2 than in controls. There were no
      differences in radius total vBMD or trabecular vBMD between groups. Despite
      inferior cortical bone properties at the radius, FEA-estimated failure load was
      similar between groups. Tibia vBMD and microarchitecture were also similar
      between groups. There were no significant associations between cortical
      parameters and duration of DM2 or HOMA-IR. However, among women with DM2, higher
      fasting glucose levels were associated with lower cortical vBMD (r=-0.54,
      p=0.018). CONCLUSIONS: DM2 and higher fasting glucose are associated with
      unfavorable cortical bone microarchitecture at the distal radius in African
      American women. These structural deficits may contribute to the increased
      fracture risk among women with DM2. Further, our results suggest that
      hyperglycemia may be involved in mechanisms of skeletal fragility associated with
      DM2.

PMID- 25398432
TI  - High-risk osteoporosis clinic (HiROC): improving osteoporosis and postfracture
      care with an organized, programmatic approach.
AB  - SUMMARY: A programmatic outpatient high-risk osteoporosis clinic (outpatient
      HiROC) and inpatient fracture liaison service (inpatient HiROC) is described.
      Results document that this population is more effectively treated and followed up
      in this specialty pathway than with primary care follow-up. INTRODUCTION: We
      describe a programmatic approach to outpatient care of high-risk osteoporosis
      patients (outpatient HiROC). We similarly describe an inpatient fracture liaison
      service (inpatient HiROC), which integrates into the existing outpatient HiROC
      pathway. METHODS: The development of outpatient HiROC and inpatient HiROC is
      described. Outpatient visits (July 29, 2008 to October 27, 2011) are included
      with a 200 patients random sample calculation. Inpatient consultation visits
      between November 18, 2008 and October 27, 2011 are included. RESULTS: Between
      July 29, 2008 and December 31, 2011, 1917 outpatient consults were seen. Of the
      200 patient samples, 87% were female, mean age of 69.8 years, previous fractures
      occurred in 34% patients, and glucocorticoid users constituted 10.6%. Eighty-six
      percent of this group was high risk, where drug therapy is indicated, and such
      treatment was started in 89%. A total of 1041 inpatient fracture consults were
      seen during the evaluable period; 14.7% of this population died before the 6
      month follow-up. Females comprised 77.6%, mean age was 76.1 years, and 58.2% of
      fractures were hip fragility, 11.6% vertebral, and 1.7% midshaft and 1.6%
      subtrochanteric. Patients seen in our outpatient HiROC pathway were significantly
      more likely to be treated than those followed up by one of our primary care
      doctors (80.6 versus 32.2%, P<0.0001). Mean vitamin D levels at baseline (27.0
      ng/mL) improved to 34.6 ng/mL at 6-month follow-up (P<0.0001). CONCLUSIONS: Our
      outpatient and inpatient HiROC model is efficient and effective in risk
      stratifying and treating patients at high risk for fractures.

PMID- 25398433
TI  - Spontaneous default mode network phase-locking moderates performance perceptions
      under stereotype threat.
AB  - This study assessed whether individual differences in self-oriented neural
      processing were associated with performance perceptions of minority students
      under stereotype threat. Resting electroencephalographic activity recorded in
      white and minority participants was used to predict later estimates of task
      errors and self-doubt on a presumed measure of intelligence. We assessed
      spontaneous phase-locking between dipole sources in left lateral parietal cortex
      (LPC), precuneus/posterior cingulate cortex (P/PCC), and medial prefrontal cortex
      (MPFC); three regions of the default mode network (DMN) that are integral for
      self-oriented processing. Results revealed that minorities with greater LPC-P/PCC
      phase-locking in the theta band reported more accurate error estimations. All
      individuals experienced less self-doubt to the extent they exhibited greater LPC
      MPFC phase-locking in the alpha band but this effect was driven by minorities.
      Minorities also reported more self-doubt to the extent they overestimated errors.
      Findings reveal novel neural moderators of stereotype threat effects on
      subjective experience. Spontaneous synchronization between DMN regions may play a
      role in anticipatory coping mechanisms that buffer individuals from stereotype
      threat. 

PMID- 25398435
TI  - Eradication of wild poliovirus type 3 may be within reach, say CDC and WHO.

PMID- 25398434
TI  - The influence of oxytocin on volitional and emotional ambivalence.
AB  - Moral decisions and social relationships are often characterized by strong
      feelings of ambivalence which can be a catalyst for emotional distress and
      several health-related problems. The anterior cingulate cortex (ACC) has been
      identified as a key brain region in monitoring conflicting information, but the
      neurobiological substrates of ambivalence processing are still widely unknown. We
      have conducted two randomized, double-blind, placebo-controlled, functional
      magnetic resonance imaging experiments involving 70 healthy male volunteers to
      investigate the effects of the neuropeptide oxytocin (OXT) on neural and
      behavioral correlates of ambivalence. We chose moral decision-making and the
      imagery of partner infidelity as examples to probe volitional and emotional
      ambivalence. In both experiments, intranasal OXT diminished neural responses in
      the ACC to ambivalence. Under OXT, moral dilemma vignettes also elicited a
      reduced activation in the orbitofrontal cortex, and the imagery of partner
      infidelity was rated as less arousing. Interestingly, the OXT-induced
      differential activation in the ACC predicted the magnitude of arousal reduction.
      Taken together, our findings reveal an unprecedented role of OXT in causing a
      domain-general decrease of neural responses to ambivalence. By alleviating
      emotional distress, OXT may qualify as a treatment option for psychiatric
      disorders with heightened ambivalence sensitivity such as schizophrenia or
      obsessive-compulsive disorder. 

PMID- 25398436
TI  - Oncolytic measles virus expressing the sodium iodide symporter to treat drug
      resistant ovarian cancer.
AB  - Edmonston vaccine strains of measles virus (MV) have significant antitumor
      activity in mouse xenograft models of ovarian cancer. MV engineered to express
      the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene
      expression and offers a tool for tumor radiovirotherapy. Here, we report results
      from a clinical evaluation of MV-NIS in patients with taxol- and platinum
      resistant ovarian cancer. MV-NIS was given intraperitoneally every 4 weeks for up
      to 6 cycles. Treatment was well tolerated and associated with promising median
      overall survival in these patients with heavily pretreated ovarian cancer; no
      dose-limiting toxicity was observed in 16 patients treated at high-dose levels
      (10(8)-10(9) TCID50), and their median overall survival of 26.5 months compared
      favorably with other contemporary series. MV receptor CD46 and nectin-4
      expression was confirmed by immunohistochemistry in patient tumors. Sodium iodide
      symporter expression in patient tumors after treatment was confirmed in three
      patients by (123)I uptake on SPECT/CTs and was associated with long progression
      free survival. Immune monitoring posttreatment showed an increase in effector T
      cells recognizing the tumor antigens IGFBP2 and FRalpha, indicating that MV-NIS
      treatment triggered cellular immunity against the patients' tumor and suggesting
      that an immune mechanism mediating the observed antitumor effect. Our findings
      support further clinical evaluation of MV-NIS as an effective immunovirotherapy.

PMID- 25398438
TI  - Intracellular Osteopontin inhibits toll-like receptor signaling and impedes liver
      carcinogenesis.
AB  - Osteopontin (OPN) has been implicated widely in tumor growth and metastasis, but
      the range of its contributions is not yet fully understood. In this study, we
      show that genetic ablation of Opn in mice sensitizes them to diethylnitrosamine
      (DEN)-induced hepatocarcinogenesis. Opn-deficient mice (Opn(-/-) mice) exhibited
      enhanced production of proinflammatory cytokines and compensatory proliferation.
      Administering OPN antibody or recombinant OPN protein to wild-type or Opn(-/-)
      mice-derived macrophages, respectively, had little effect on cytokine production.
      In contrast, overexpression of intracellular OPN (iOPN) in Opn-deficient
      macrophages strongly suppressed production of proinflammatory cytokines. In
      addition, we found that iOPN was able to interact with the pivotal Toll-like
      receptor (TLR) signaling protein MyD88 in macrophages after stimulation with
      cellular debris, thereby disrupting TLR signaling in macrophages. Our results
      indicated that iOPN was capable of functioning as an endogenous negative
      regulator of TLR-mediated immune responses, acting to ameliorate production of
      proinflammatory cytokines and curtail DEN-induced hepatocarcinogenesis. Together,
      our results expand the important role of OPN in inflammation-associated cancers
      and deepen its relevance for novel treatment strategies in liver cancer.

PMID- 25398437
TI  - Mdm2 and aurora kinase a inhibitors synergize to block melanoma growth by driving
      apoptosis and immune clearance of tumor cells.
AB  - Therapeutics that induce cancer cell senescence can block cell proliferation and
      promote immune rejection. However, the risk of tumor relapse due to senescence
      escape may remain high due to the long lifespan of senescent cells that are not
      cleared. Here, we show how combining a senescence-inducing inhibitor of the
      mitotic kinase Aurora A (AURKA) with an MDM2 antagonist activates p53 in
      senescent tumors harboring wild-type 53. In the model studied, this effect is
      accompanied by proliferation arrest, mitochondrial depolarization, apoptosis, and
      immune clearance of cancer cells by antitumor leukocytes in a manner reliant upon
      Ccl5, Ccl1, and Cxcl9. The AURKA/MDM2 combination therapy shows adequate
      bioavailability and low toxicity to the host. Moreover, the prominent response of
      patient-derived melanoma tumors to coadministered MDM2 and AURKA inhibitors
      offers a sound rationale for clinical evaluation. Taken together, our work
      provides a preclinical proof of concept for a combination treatment that
      leverages both senescence and immune surveillance to therapeutic ends.

PMID- 25398439
TI  - PLK1 phosphorylates PAX3-FOXO1, the inhibition of which triggers regression of
      alveolar Rhabdomyosarcoma.
AB  - Pediatric tumors harbor very low numbers of somatic mutations and therefore offer
      few targets to improve therapeutic management with targeted drugs. In particular,
      outcomes remain dismal for patients with metastatic alveolar rhabdomyosarcoma
      (aRMS), where the chimeric transcription factor PAX3/7-FOXO1 has been implicated
      but problematic to target. In this report, we addressed this challenge by
      developing a two-armed screen for druggable upstream regulatory kinases in the
      PAX3/7-FOXO1 pathway. Screening libraries of kinome siRNA and small molecules, we
      defined PLK1 as an upstream-acting regulator. Mechanistically, PLK1 interacted
      with and phosphorylated PAX3-FOXO1 at the novel site S503, leading to protein
      stabilization. Notably, PLK1 inhibition led to elevated ubiquitination and rapid
      proteasomal degradation of the PAX3-FOXO1 chimeric oncoprotein. On this basis, we
      embarked on a preclinical validation of PLK1 as a target in a xenograft mouse
      model of aRMS, where the PLK1 inhibitor BI 2536 reduced PAX3-FOXO1-mediated gene
      expression and elicited tumor regression. Clinically, analysis of human aRMS
      tumor biopsies documented high PLK1 expression to offer prognostic significance
      for both event-free survival and overall survival. Taken together, these
      preclinical studies validate the PLK1-PAX3-FOXO1 axis as a rational target to
      treat aRMS.

PMID- 25398440
TI  - Tropomodulin 1 expression driven by NF-kappaB enhances breast cancer growth.
AB  - Triple-negative breast cancers (TNBC), which include the basal-like and claudin
      low disease subtypes, are aggressive malignancies for which effective therapeutic
      targets are lacking. NF-kappaB activation has an established role in breast
      malignancy, and it is higher in TNBC than other breast cancer subtypes. On this
      basis, we hypothesized that proteins derived from NF-kappaB target genes might be
      molecular targets for TNBC therapy. In this study, we conducted a microarray
      based screen for novel NF-kappaB-inducible proteins as candidate therapeutic
      targets, identifying tropomodulin 1 (TMOD1) as a lead candidate. TMOD1 expression
      was regulated directly by NF-kappaB and was significantly higher in TNBC than
      other breast cancer subtypes. TMOD1 elevation is associated with enhanced tumor
      growth in a mouse tumor xenograft model and in a 3D type I collagen culture.
      TMOD1-dependent tumor growth was correlated with MMP13 induction, which was
      mediated by TMOD1-dependent accumulation of beta-catenin. Overall, our study
      highlighted a novel TMOD1-mediated link between NF-kappaB activation and MMP13
      induction, which accounts in part for the NF-kappaB-dependent malignant phenotype
      of TNBC.

PMID- 25398441
TI  - Do nurses reason 'adaptively' in time limited situations: the findings of a
      descriptive regression analysis.
AB  - BACKGROUND: Time pressure is common in acute healthcare and significantly
      influences clinical judgement and decision making. Despite nurses' judgements
      being studied since the 1960s, the empirical picture of how time pressure impacts
      on nurses' judgement strategies and outcomes remain undeveloped. This paper aims
      to assess alterations in nurses' judgement strategies and outcomes under time
      pressure in a simulated acute care setting. METHODS: In a simulated acute care
      environment, ninety-seven nurses were exposed to 25 clinical scenarios under time
      pressured and no time pressured conditions. Scenarios were randomly sampled from
      a large dataset of patient cases. A reference standard (judgement correctness)
      was generated from the same patient case records. In 12 of the scenarios only 20
      seconds per judgement was allowed, in the other 13 scenarios no time pressure
      existed. Percentage of correct judgments in both conditions was calculated.
      Logistic regression modelling (of 2,425 observations) described the relationship
      between information cues used and judgments made. The degree of attention paid to
      particular cues was captured by calculating cue relative weights. The clustering
      effect of nurses was countered by estimating robust standard errors. The Chow
      test was used to test the null hypothesis that differences in regression
      coefficients in time pressure and no time pressure models were zero. RESULTS:
      Compared to no time pressure, no significant difference was observed in the
      proportion of correct judgments when nurses were put under time pressure.
      However, time pressure significantly impacted on the judgment strategies
      employed. Whilst nurses predominantly used respiration rate to make judgements,
      they used fewer cues to reach their clinical judgements under time pressure. The
      relative weighting afforded to heart rate was much smaller in the time pressure
      regression model, indicating that nurses paid significantly less attention to it
      when making judgements under time pressure. CONCLUSIONS: Time pressure had a
      significant effect on nurses' judgement strategies but not outcomes. Nurses
      tended to use less information to reach judgements under time pressure, but not
      at the expense of judgment accuracy. Findings imply that nurses are capable of
      using adaptive judgement strategies to cope with moderate time pressures when
      making clinical judgements in acute care.

PMID- 25398442
TI  - Osteotomies in proximal junctional kyphosis in the cervicothoracic area.
AB  - INTRODUCTION: Proximal junctional kyphosis (PJK) of the cervicothoracic spine is
      a deformity that can affect patients who have undergone long thoracolumbar
      instrumented fusion. Preoperative hyperkyphosis of the thoracic spine and changes
      of more than 30 degrees  in lumbar lordosis are independent risk factors for the
      onset of PJK. METHODS: When PJK occurs in the cervicothoracic spine, extension of
      the fusion with eventual application of osteotomy techniques is frequently
      necessary to treat symptomatic patients or in case a neurological deficit occurs.
      Ponte osteotomy and pedicle subtraction osteotomy (PSO) are the two most used
      techniques to restore a good cervicothoracic alignment, although they are still
      demanding procedures even for expert surgeons. In junctional fractures, a
      vertebral column resection can be performed to support the anterior column. Ponte
      osteotomy ideally restores 10 degrees  at each treated level, while PSO allows a
      segmental correction up to 30 degrees -35 degrees . Adequate preoperative
      planning is fundamental for outlining the correct surgery and choosing the
      appropriate osteotomy. CONCLUSIONS: The aim of corrective surgery is to restore
      the cervicothoracic alignment, obtaining an adequate postoperative sagittal
      balance and decreasing the risk of further complications and new revision
      surgeries.

PMID- 25398443
TI  - Rosai-Dorfman disease with spinal cord compression: a diagnostic challenge.
AB  - PURPOSE: Rosai-Dorfman disease (RDD) is an uncommon benign histiocytic
      proliferative disorder commonly involving the cervical lymph nodes and less
      frequently extranodal sites, including, rarely, the central nervous system,
      mainly intracranially. Spinal involvement is unusual. RDD is characterized by
      pathognomonic histopathological features, which are decisive in the definitive
      diagnosis. We present the case of a 75-year-old lady who presented with an
      isolated thoracic vertebral lesion. She underwent 3 CT-guided biopsies, all not
      confirmative for a definite diagnosis, and 2 open biopsies and debulking of the
      lesion. METHODS: The clinical notes, operation notes, investigations and clinic
      letters of the patient were reviewed. A literature search was performed using
      PubMed, with the keywords "Rosai-Dorfman disease", "sinus histiocytosis with
      massive lymphadenopathy", "histiocytic proliferative disorder". RESULTS: Only the
      histopathology after the last procedure was diagnostic for Rosai-Dorfman disease.
      The patient was treated with steroids with marked improvement in her clinical
      condition. CONCLUSIONS: This case demonstrates the challenge in making a
      diagnosis. RDD should be considered as a differential diagnosis in case of spinal
      lesion and non-diagnostic biopsy, especially in steroid sensitive lesions. The
      implications of the case are discussed.

PMID- 25398444
TI  - Integrating fossils, phylogenies, and niche models into biogeography to reveal
      ancient evolutionary history: the case of Hypericum (hypericaceae).
AB  - In disciplines such as macroevolution that are not amenable to experimentation,
      scientists usually rely on current observations to test hypotheses about
      historical events, assuming that "the present is the key to the past."
      Biogeographers, for example, used this assumption to reconstruct ancestral ranges
      from the distribution of extant species. Yet, under scenarios of high extinction
      rates, the biodiversity we observe today might not be representative of the
      historical diversity and this could result in incorrect biogeographic
      reconstructions. Here, we introduce a new approach to incorporate into
      biogeographic inference the temporal, spatial, and environmental information
      provided by the fossil record, as a direct evidence of the extinct biodiversity
      fraction. First, inferences of ancestral ranges for those nodes in the phylogeny
      calibrated with the fossil record are constrained to include the geographic
      distribution of the fossil. Second, we use fossil distribution and past climate
      data to reconstruct the climatic preferences and potential distribution of
      ancestral lineages over time, and use this information to build a biogeographic
      model that takes into account "ecological connectivity" through time. To show the
      power of this approach, we reconstruct the biogeographic history of the large
      angiosperm genus Hypericum, which has a fossil record extending back to the Early
      Cenozoic. Unlike previous reconstructions based on extant species distributions,
      our results reveal that Hypericum stem lineages were already distributed in the
      Holarctic before diversification of its crown-group, and that the geographic
      distribution of the genus has been relatively stable throughout the climatic
      oscillations of the Cenozoic. Geographical movement was mediated by the existence
      of climatic corridors, like Beringia, whereas the equatorial tropical belt acted
      as a climatic barrier, preventing Hypericum lineages to reach the southern
      temperate regions. Our study shows that an integrative approach to historical
      biogeography-that combines sources of evidence as diverse as paleontology,
      ecology, and phylogenetics-could help us obtain more accurate reconstructions of
      ancient evolutionary history. It also reveals the confounding effect different
      rates of extinction across regions have in biogeography, sometimes leading to
      ancestral areas being erroneously inferred as recent colonization events. 

PMID- 25398445
TI  - Calibrated birth-death phylogenetic time-tree priors for bayesian inference.
AB  - Here we introduce a general class of multiple calibration birth-death tree priors
      for use in Bayesian phylogenetic inference. All tree priors in this class
      separate ancestral node heights into a set of "calibrated nodes" and
      "uncalibrated nodes" such that the marginal distribution of the calibrated nodes
      is user-specified whereas the density ratio of the birth-death prior is retained
      for trees with equal values for the calibrated nodes. We describe two
      formulations, one in which the calibration information informs the prior on
      ranked tree topologies, through the (conditional) prior, and the other which
      factorizes the prior on divergence times and ranked topologies, thus allowing
      uniform, or any arbitrary prior distribution on ranked topologies. Although the
      first of these formulations has some attractive properties, the algorithm we
      present for computing its prior density is computationally intensive. However,
      the second formulation is always faster and computationally efficient for up to
      six calibrations. We demonstrate the utility of the new class of multiple
      calibration tree priors using both small simulations and a real-world analysis
      and compare the results to existing schemes. The two new calibrated tree priors
      described in this article offer greater flexibility and control of prior
      specification in calibrated time-tree inference and divergence time dating, and
      will remove the need for indirect approaches to the assessment of the combined
      effect of calibration densities and tree priors in Bayesian phylogenetic
      inference. 

PMID- 25398446
TI  - Risk factors for long-bone fractures in children up to 5 years of age: a nested
      case-control study.
AB  - AIM: To investigate risk factors for first long-bone fractures in children up to
      5 years old in order to provide evidence about which families could benefit from
      injury prevention interventions. METHODS: Population-based matched nested case
      control study using The Health Improvement Network, a UK primary care research
      database, 1988-2004. Maternal, household and child risk factors for injury were
      assessed among 2456 children with long-bone fractures (cases). 23,661 controls
      were matched to cases on general practice. Adjusted ORs and 95% CIs were
      estimated using conditional logistic regression. RESULTS: Fractures of long-bones
      were independently associated with younger maternal age and higher birth order,
      with children who were the fourth-born in the family, or later, having a
      threefold greater odds of fracture compared to first-born children (adjusted OR
      3.12, 95% CI 2.08 to 4.68). Children over the age of 1 year had a fourfold (13-24
      months, adjusted OR 4.09 95% CI 3.51 to 4.76) to fivefold (37+ months, adjusted
      OR 4.88 95% CI 4.21 to 5.66) increase in the odds of a long-bone fracture
      compared to children aged 0-12 months. Children in families with a history of
      maternal alcohol misuse had a raised odds of long-bone fracture (adjusted OR
      2.33, 95% CI 1.13 to 4.82) compared to those with no documented history.
      CONCLUSIONS: Risk factors for long-bone fractures in children less than 5 years
      old included age above 1 year, increasing birth order, younger maternal age and
      maternal alcohol misuse. These risk factors should be used to prioritise families
      and communities for injury prevention interventions.

PMID- 25398448
TI  - Infantile sucking bruises.

PMID- 25398447
TI  - Obsessive-compulsive disorder in children and adolescents.
AB  - Obsessive-compulsive disorder (OCD) in childhood and adolescence is an impairing
      condition, associated with a specific set of distressing symptoms incorporating
      repetitive, intrusive thoughts (obsessions) and distressing, time-consuming
      rituals (compulsions). This review considers current knowledge of causes and
      mechanisms underlying OCD, as well as assessment and treatment. Issues relating
      to differential diagnosis are summarised, including the challenges of
      distinguishing OCD from autism spectrum disorders and tic disorders in youth. The
      recommended treatments, namely cognitive behaviour therapy and serotonin reuptake
      inhibiting/selective serotonin reuptake inhibitor medications, are outlined along
      with the existing evidence-based and factors associated with treatment
      resistance. Finally, novel clinical developments that are emerging in the field
      and future directions for research are discussed. 

PMID- 25398449
TI  - A first-in-human phase I study of MORAb-004, a monoclonal antibody to endosialin
      in patients with advanced solid tumors.
AB  - PURPOSE: Endosialin (TEM-1, CD248) is a protein expressed on the surface of
      activated mesenchymal cells, including certain subsets of tumors. Preclinical
      models suppressing endosialin function have shown antitumor activity. A humanized
      monoclonal antibody, MORAb-004, was engineered to target endosialin and is the
      first agent in clinical development for this mesenchymal cell target.
      EXPERIMENTAL DESIGN: This first-in-human, open-label, phase I study recruited
      patients with treatment-refractory solid tumors. MORAb-004 was administered
      intravenously once weekly in 4-week cycles. Objectives included determination of
      the safety of multiple infusions of MORAb-004, identification of the maximum
      tolerated dose (MTD), pharmacokinetic modeling, detection of any anti-human
      antibody response, and assessment of objective radiographic response to therapy.
      RESULTS: Thirty-six patients were treated at 10 dose levels of MORAb-004, ranging
      from 0.0625 to 16 mg/kg. Drug-related adverse events were primarily grade 1-2
      infusion toxicities. Dose-limiting toxicity of grade 3 vomiting was observed at
      16 mg/kg. Eighteen of 32 evaluable patients across all doses achieved disease
      stability, with minor radiographic responses observed in 4 patients (pancreatic
      neuroendocrine, hepatocellular, and sarcoma tumor types). Pharmacokinetics showed
      MORAb-004 accumulation beginning at 4 mg/kg and saturable elimination beginning
      at 0.25 mg/kg. Exposure increased in a greater-than-dose-proportional manner with
      terminal half-life increasing proportionally with dose. The MTD was identified as
      12 mg/kg. CONCLUSIONS: Preliminary antitumor activity was observed. Safety
      profile, pharmacokinetics, and early antitumor activity suggest that MORAb-004 is
      safe at doses up to 12 mg/kg and should be studied further for efficacy.

PMID- 25398450
TI  - Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno
      Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and
      Bortezomib.
AB  - PURPOSE: Novel therapeutic agents have significantly improved the survival of
      patients with multiple myeloma. Nonetheless, the prognosis of patients with
      multiple myeloma who become refractory to the novel agents lenalidomide and
      bortezomib is very poor, indicating the urgent need for new therapeutic options
      for these patients. The human CD38 monoclonal antibody daratumumab is being
      evaluated as a novel therapy for multiple myeloma. Prompted with the encouraging
      results of ongoing clinical phase I/II trials, we now addressed the potential
      value of daratumumab alone or in combination with lenalidomide or bortezomib for
      the treatment of lenalidomide- and bortezomib-refractory patients. EXPERIMENTAL
      DESIGN: In ex vivo assays, mainly evaluating antibody-dependent cell-mediated
      cytotoxicity, and in an in vivo xenograft mouse model, we evaluated daratumumab
      alone or in combination with lenalidomide or bortezomib as a potential therapy
      for lenalidomide- and bortezomib-refractory multiple myeloma patients. RESULTS:
      Daratumumab induced significant lysis of lenalidomide/bortezomib-resistant
      multiple myeloma cell lines and of primary multiple myeloma cells in the bone
      marrow mononuclear cells derived from lenalidomide- and/or bortezomib-refractory
      patients. In these assays, lenalidomide but not bortezomib, synergistically
      enhanced daratumumab-mediated multiple myeloma lysis through activation of
      natural killer cells. Finally, in an in vivo xenograft model, only the
      combination of daratumumab with lenalidomide effectively reduced the tumorigenic
      growth of primary multiple myeloma cells from a lenalidomide- and bortezomib
      refractory patient. CONCLUSIONS: Our results provide the first preclinical
      evidence for the benefit of daratumumab plus lenalidomide combination for
      lenalidomide- and bortezomib-refractory patients.

PMID- 25398452
TI  - Whole-exome sequencing reveals defective CYP3A4 variants predictive of paclitaxel
      dose-limiting neuropathy.
AB  - PURPOSE: Paclitaxel, a widely used chemotherapeutic drug, can cause peripheral
      neuropathies leading to dose reductions and treatment suspensions and decreasing
      the quality of life of patients. It has been suggested that genetic variants
      altering paclitaxel pharmacokinetics increase neuropathy risk, but the major
      causes of interindividual differences in susceptibility to paclitaxel toxicity
      remain unexplained. We carried out a whole-exome sequencing (WES) study to
      identify genetic susceptibility variants associated with paclitaxel neuropathy.
      EXPERIMENTAL DESIGN: Blood samples from 8 patients with severe paclitaxel-induced
      peripheral neuropathy were selected for WES. An independent cohort of 228 cancer
      patients with complete paclitaxel neuropathy data was used for variant screening
      by DHPLC and association analysis. HEK293 cells were used for heterologous
      expression and characterization of two novel CYP3A4 enzymes. RESULTS: WES
      revealed 2 patients with rare CYP3A4 variants, a premature stop codon (CYP3A4*20
      allele) and a novel missense variant (CYP3A4*25, p.P389S) causing reduced enzyme
      expression. Screening for CYP3A4 variants in the independent cohort revealed
      three additional CYP3A4*20 carriers, and two patients with missense variants
      exhibiting diminished enzyme activity (CYP3A4*8 and the novel CYP3A4*27 allele,
      p.L475V). Relative to CYP3A4 wild-type patients, those carrying CYP3A4 defective
      variants had more severe neuropathy (2- and 1.3-fold higher risk of neuropathy
      for loss-of-function and missense variants, respectively, P = 0.045) and higher
      probability of neuropathy-induced paclitaxel treatment modifications (7- and 3
      fold higher risk for loss-of-function and missense variants, respectively, P =
      5.9 * 10(-5)). CONCLUSION: This is the first description of a genetic marker
      associated with paclitaxel treatment modifications caused by neuropathy. CYP3A4
      defective variants may provide a basis for paclitaxel treatment
      individualization.

PMID- 25398451
TI  - Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed
      with epithelial ovarian cancer.
AB  - PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on
      mortality in patients with ovarian cancer up to 10 years after diagnosis.
      EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients
      from two case-control studies and extended survival time data for 4,314 patients
      from previously reported studies. All participants had been screened for
      deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for
      the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as
      time-varying covariates. Competing risks were analyzed using Fine and Gray model.
      RESULTS: The combined 10-year overall survival rate was 30% [95% confidence
      interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1
      carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53
      at time zero and increased over time becoming greater than one at 4.8 years. For
      BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become
      greater than 1 at 10.5 years). The results were similar when restricted to 3,202
      patients with high-grade serous tumors and to ovarian cancer-specific mortality.
      CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival,
      but this advantage decreases over time and in BRCA1 carriers is eventually
      reversed. This may have important implications for therapy of both primary and
      relapsed disease and for analysis of long-term survival in clinical trials of new
      agents, particularly those that are effective in BRCA1/2 mutation carriers.

PMID- 25398453
TI  - Antiproliferative Effect of Lapatinib in HER2-Positive and HER2-Negative/HER3
      High Breast Cancer: Results of the Presurgical Randomized MAPLE Trial (CRUK
      E/06/039).
AB  - PURPOSE: Not all breast cancers respond to lapatinib. A change in Ki67 after
      short-term exposure may elucidate a biomarker profile for responsive versus
      nonresponsive tumors. EXPERIMENTAL DESIGN: Women with primary breast cancer were
      randomized (3:1) to 10 to 14 days of preoperative lapatinib or placebo in a
      multicenter phase II trial (ISRCTN68509377). Biopsies pre-/posttreatment were
      analyzed for Ki67, apoptosis, HER2, EGFR, ER, PgR, pAKT, pERK, and stathmin by
      IHC. Further markers were measured by RT-PCR. Primary endpoint was change in
      Ki67. HER2(+) was defined as 2+/3+ by IHC and FISH(+). RESULTS: One hundred
      twenty-one patients (lapatinib, 94; placebo, 27) were randomized; of these, 21%
      were HER2(+), 78% were HER2(-) nonamplified, 26% were EGFR(+). Paired samples
      containing tumor were obtained for 98% (118 of 121). Ki67 fell significantly with
      lapatinib (-31%; P < 0.001), but not with placebo (-3%). Whereas Ki67 reduction
      with lapatinib was greatest in HER2(+) breast cancer (-46%; P = 0.003), there was
      a significant Ki67 decrease in HER2(-) breast cancer (-27%; P = 0.017) with 14%
      of HER2(-) breast cancer demonstrating >=50% Ki67 reduction with lapatinib. Among
      HER2(+) patients, the only biomarker predictive of Ki67 response was the
      EGFR/HER4 ligand epiregulin (EREG) (rho = -0.7; P = 0.002). Among HER2(-) tumors,
      only HER3 mRNA levels were significantly associated with Ki67 response on
      multivariate analysis (P = 0.01). In HER2(-) breast cancer, HER2 and HER3 mRNA
      levels were highly correlated (rho = 0.67, P < 0.001), with all Ki67 responders
      having elevated HER3 and HER2 expression. CONCLUSIONS: Lapatinib has
      antiproliferative effects in a subgroup of HER2(-) nonamplified tumors
      characterized by high HER3 expression. The possible role of high HER2:HER3
      heterodimers in predicting response to lapatinib merits investigation in HER2(-)
      tumors.

PMID- 25398455
TI  - Exosomes secreted by cortical neurons upon glutamatergic synapse activation
      specifically interact with neurons.
AB  - Exosomes are nano-sized vesicles of endocytic origin released into the
      extracellular space upon fusion of multivesicular bodies with the plasma
      membrane. Exosomes represent a novel mechanism of cell-cell communication
      allowing direct transfer of proteins, lipids and RNAs. In the nervous system,
      both glial and neuronal cells secrete exosomes in a way regulated by glutamate.
      It has been hypothesized that exosomes can be used for interneuronal
      communication implying that neuronal exosomes should bind to other neurons with
      some kind of specificity. Here, dissociated hippocampal cells were used to
      compare the specificity of binding of exosomes secreted by neuroblastoma cells to
      that of exosomes secreted by cortical neurons. We found that exosomes from
      neuroblastoma cells bind indiscriminately to neurons and glial cells and could be
      endocytosed preferentially by glial cells. In contrast, exosomes secreted from
      stimulated cortical neurons bound to and were endocytosed only by neurons. Thus,
      our results demonstrate for the first time that exosomes released upon synaptic
      activation do not bind to glial cells but selectively to other neurons suggesting
      that they can underlie a novel aspect of interneuronal communication. 

PMID- 25398454
TI  - Potentially effective natural drugs in treatment for the most common rheumatic
      disorder: osteoarthritis.
AB  - Osteoarthritis (OA) is a chronic condition in which imbalance between anabolic
      and catabolic mediators occurs leading to the destruction of homeostasis of
      articular cartilage. The current drugs in the management of OA can just alleviate
      symptoms. Hence, the research tendency toward exploration of novel sources has
      been grown up in order to achieve safe and efficacious drugs. Meanwhile, various
      components exist as novel natural drugs that may possess favorable properties for
      the management of OA. This review focuses on the most efficacious medicinal
      plants and their phytochemical agents, which have been consumed for the
      management of OA. Moreover, evaluation of their efficacy and molecular mechanisms
      of action are discussed based on numerous modern experimental investigations.
      More research is needed to develop therapeutic agents with disease-modifying
      properties to treat OA. 

PMID- 25398456
TI  - IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection
      After Solid-Organ Transplantation.
AB  - BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been
      associated with susceptibility to invasive mold infection (IMI) among
      hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS:
      Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT
      recipients (715 kidney transplant recipients, 190 liver transplant recipients,
      102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients
      of other transplants) from the Swiss Transplant Cohort Study. Association between
      SNPs and the end point were assessed by log-rank test and Cox regression models.
      Cytokine production upon Aspergillus stimulation was measured by enzyme-linked
      immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy
      volunteers and correlated with relevant genotypes. RESULTS: Mold colonization (n
      = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the
      genes encoding interleukin 1beta (IL1B; rs16944; recessive mode, P = .001 for
      colonization and P = .00005 for IMI, by the log-rank test), interleukin 1
      receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and
      beta-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The
      associations with IL1B and DEFB1 remained significant in a multivariate
      regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The
      presence of 2 copies of the rare allele of rs16944 or rs419598 was associated
      with reduced Aspergillus-induced interleukin 1beta and tumor necrosis factor
      alpha secretion by PBMCs. CONCLUSIONS: Functional polymorphisms in IL1B and DEFB1
      influence susceptibility to mold infection in SOT recipients. This observation
      may contribute to individual risk stratification.

PMID- 25398457
TI  - Immunophenotype and function of CD38-expressing CD4+ and CD8+ T cells in HIV
      infected patients undergoing suppressive combination antiretroviral therapy.

PMID- 25398458
TI  - Reply to Cannizzo et al.

PMID- 25398459
TI  - Transcriptional changes that characterize the immune reactions of leprosy.
AB  - BACKGROUND: Leprosy morbidity is increased by 2 pathologic immune reactions,
      reversal reaction (RR) and erythema nodosum leprosum (ENL). METHODS: To discover
      host factors related to immune reactions, global transcriptional profiles of
      peripheral blood mononuclear cells were compared between 11 RR, 11 ENL, and 19
      matched control patients, with confirmation by quantitative polymerase chain
      reaction. Encoded proteins were investigated in skin biopsy specimens by means of
      immunohistochemistry. RESULTS: There were 275 genes differentially expressed in
      RR and 517 differentially expressed in ENL on the microarray. Pathway analysis
      showed immunity-related pathways represented in RR and ENL transcriptional
      profiles, with the "complement and coagulation" pathway common to both.
      Interferon gamma was identified as a significant upstream regulator of the
      expression changes for RR and ENL. Immunohistochemical staining of skin lesions
      showed increased C1q in both RR and ENL. CONCLUSIONS: These data suggest a
      previously underrecognized role for complement in the pathogenesis of both RR and
      ENL, and we propose new hypotheses for reaction pathogenesis.

PMID- 25398460
TI  - Differences in HIV type 1 neutralization breadth in 2 geographically distinct
      cohorts in Africa.
AB  - To investigate whether distinct populations have differing human immunodeficiency
      virus type 1 (HIV) neutralizing antibody responses, we compared 20 women from
      Tanzania's HIV Superinfection Study (HISIS) cohort, who were infected multiple
      HIV subtypes, and 22 women from the Centre for the AIDS Programme of Research in
      South Africa (CAPRISA) cohort, who were infected exclusively with HIV subtype C.
      By 2 years after infection, 35% of HISIS subjects developed neutralization
      breadth, compared with 9% of CAPRISA subjects (P = .0131). Cumulative viral loads
      between 3 and 12 months were higher in the HISIS group (P = .046) and strongly
      associated with breadth (P < .0001). While viral load was the strongest
      predictor, other factors may play a role, as the odds of developing breadth
      remained higher in HISIS even after correction for viral load. 

PMID- 25398461
TI  - An unusual presentation of amyloidosis.

PMID- 25398462
TI  - Unintentional child neglect: literature review and observational study.
AB  - Child abuse is a problem that affects over six million children in the United
      States each year. Child neglect accounts for 78% of those cases. Despite this,
      the issue of child neglect is still not well understood, partially because child
      neglect does not have a consistent, universally accepted definition. Some
      researchers consider child neglect and child abuse to be one in the same, while
      other researchers consider them to be conceptually different. Factors that make
      child neglect difficult to define include: (1) Cultural differences; motives must
      be taken into account because parents may believe they are acting in the child's
      best interests based on cultural beliefs (2) the fact that the effect of child
      abuse is not always immediately visible; the effects of emotional neglect
      specifically may not be apparent until later in the child's development, and (3)
      the large spectrum of actions that fall under the category of child abuse. Some
      of the risk factors for increased child neglect and maltreatment have been
      identified. These risk factors include socioeconomic status, education level,
      family composition, and the presence of dysfunction family characteristics.
      Studies have found that children from poorer families and children of less
      educated parents are more likely to sustain fatal unintentional injuries than
      children of wealthier, better educated parents. Studies have also found that
      children living with adults unrelated to them are at increased risk for
      unintentional injuries and maltreatment. Dysfunctional family characteristics may
      even be more indicative of child neglect. Parental alcohol or drug abuse,
      parental personal history of neglect, and parental stress greatly increase the
      odds of neglect. Parental depression doubles the odds of child neglect. However,
      more research needs to be done to better understand these risk factors and to
      identify others. Having a clearer understanding of the risk factors could lead to
      prevention and treatment, as it would allow for health care personnel to screen
      for high-risk children and intervene before it is too late. Screening could also
      be done in the schools and organized after school activities. Parenting classes
      have been shown to be an effective intervention strategy by decreasing parental
      stress and potential for abuse, but there has been limited research done on this
      approach. Parenting classes can be part of the corrective actions for parents
      found to be neglectful or abusive, but parenting classes may also be useful as a
      preventative measure, being taught in schools or readily available in higher-risk
      communities. More research has to be done to better define child abuse and
      neglect so that it can be effectively addressed and treated.

PMID- 25398463
TI  - The effect of intermittent preventive treatment on anti-malarial drug resistance
      spread in areas with population movement.
AB  - BACKGROUND: The use of intermittent preventive treatment in pregnant women
      (IPTp), children (IPTc) and infant (IPTi) is an increasingly popular preventive
      strategy aimed at reducing malaria risk in these vulnerable groups. Studies to
      understand how this preventive intervention can affect the spread of anti
      malarial drug resistance are important especially when there is human movement
      between neighbouring low and high transmission areas. Because the same drug is
      sometimes utilized for IPTi and for symptomatic malaria treatment, distinguishing
      their individual roles on accelerating the spread of drug resistant malaria, with
      or without human movement, may be difficult to isolate experimentally or by
      analysing data. A theoretical framework, as presented here, is thus relevant as
      the role of IPTi on accelerating the spread of drug resistance can be isolated in
      individual populations and when the populations are interconnected and interact.
      METHODS: A previously published model is expanded to include human movement
      between neighbouring high and low transmission areas, with focus placed on the
      malaria parasites. Parasite fitness functions, determined by how many humans the
      parasites can infect, are used to investigate how fast resistance can spread
      within the neighbouring communities linked by movement, when the populations are
      at endemic equilibrium. RESULTS: Model simulations indicate that population
      movement results in resistance spreading fastest in high transmission areas, and
      the more complete the anti-malarial resistance the faster the resistant parasite
      will tend to spread through a population. Moreover, the demography of infection
      in low transmission areas tends to change to reflect the demography of high
      transmission areas. Additionally, when regions are strongly connected the rate of
      spread of partially resistant parasites (R1) relative to drug sensitive parasites
      (RS), and fully resistant parasites (R2) relative to partially resistant
      parasites (R1) tend to behave the same in both populations, as should be
      expected. CONCLUSIONS: In fighting anti-malarial drug resistance, different drug
      resistance monitoring and management policies are needed when the area in
      question is an isolated high or low transmission area, or when it is close and
      interacting with a neighbouring high or low transmission area, with human
      movement between them.

PMID- 25398464
TI  - Treatment of mood disorders in multiple sclerosis.
AB  - OPINION STATEMENT: Multiple sclerosis (MS) is a chronic demyelinating disease of
      the central nervous system with a significant comorbidity with depressive
      disorders. Prevalence rates for major depressive disorder (MDD) range from 36 %
      to 54 % and the rate is around 22 % for adjustment disorders. Selective serotonin
      reuptake inhibitors (SSRIs) are considered well-tolerated first-line treatment.
      Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are
      generally reserved for second-line use after SSRIs, because of sedating or
      anticholinergic side effects. SNRIs, with the exception of duloxetine, and
      combinations of newer antidepressants have failed to treat depression due to
      their side effects profile and frequent interaction with other drugs. Among
      SSRIs, sertraline is usually the first option, starting at 25 mg/day and
      increasing to 50 mg/day; and waiting a few weeks to assess drug effects before
      increasing the dose. The maximum is generally 200 mg/day in a single dose.
      Paroxetine is the second choice, starting at 10 mg/day for the first 5 days, and
      then at 20 mg/day thereafter. The maximum dose is about 50 mg/day in a single
      dose. Fluvoxamine is used at 100-200 mg/day, starting with 25 mg/day, and
      increasing 25 mg/day every 5 days until 200 mg/day is reached. We should take
      into account increasing blood level amounts of MS treatments (corticosteroids and
      cyclophosphamide) with fluvoxamine. With duloxetine, doses will be at 60-120
      mg/day. The initial dose for depression is 40 mg/day in two doses; it can
      increase to 60 mg/day in one to two doses if necessary. The maximum dose is
      generally 120 mg/day. Duloxetine may increase liver problems through interaction
      with these MS treatments: teriflunomide, interferon beta-1a, and interferon beta
      1b. Considering psychotherapy, only cognitive behavior therapy and mindfulness
      based interventions have shown efficacy in improving depression disorders in MS.
      A comprehensive treatment for depression should include pharmacotherapy and
      psychotherapy.

PMID- 25398465
TI  - Current role of chemotherapy and bone marrow transplantation in multiple
      sclerosis.
AB  - OPINION STATEMENT: The range of available treatment options for patients with
      multiple sclerosis (MS) has expanded tremendously in recent years, adding further
      complexity to the therapeutic decision-making process. The first-generation
      therapies interferon beta and glatiramer acetate have been safely used for more
      than 20 years, but are only partially effective. Many of the newly approved MS
      therapies such as oral agents and monoclonal antibodies are selective
      immunosuppressants that appear to have improved efficacy and/or are more
      convenient, albeit in the absence of a long-term safety record. Although some are
      known to be associated with serious adverse effects, these treatments provide
      evidence-based therapeutic options for patients with suboptimal response or
      breakthrough disease. In this new scenario, non-selective immunosuppressive drugs
      and autologous hematopoietic stem cell transplantation are still present but
      likely play a more limited role than before. In this review, we briefly summarize
      the current, recent, and most imminent immunosuppressive therapies, and present
      an overall summary along with a discussion of their role in the current MS
      treatment scenario.

PMID- 25398466
TI  - In search of a treatment for radiation-induced optic neuropathy.
AB  - OPINION STATEMENT: Radiation-induced optic neuropathy (RON) is an iatrogenic
      complication that causes severe, irreversible vision loss in one or both eyes
      within the months to years following radiation therapy. Posterior RON is a rare
      but devastating toxicity of radiation applied to the visual pathways to treat
      paranasal sinus and skull base tumors. Anterior RON is an unavoidable consequence
      of proton beam irradiation or ophthalmic plaque treatment of orbital, choroidal,
      or retinal tumors. Various treatments aimed at stabilizing and ideally reversing
      vision loss have been investigated but only in small cases series. Systemic
      corticosteroids and anticoagulants, which are moderately effective when used for
      cerebral radiation necrosis, have shown no signs of benefit for RON. Hyperbaric
      oxygen therapy may promote short-term, partial recovery of vision in select
      patients, especially at partial pressures of at least 2.4 atm and when
      administered early after symptom onset. Reversal of visual deficits through
      treatment with systemic bevacizumab has been reported, but until controlled
      studies are performed, the side effect profile of stroke and myocardial
      infarction should limit its use in a population with predisposing cardiovascular
      risk factors. Intravitreal bevacizumab has shown promising results in patients
      with anterior RON, but repeated, long-term injections are required for sustained
      effect. As no intervention has been clearly shown to halt or reverse vision loss,
      larger prospective studies are needed to validate observed benefits for any of
      the treatments that have been described.

PMID- 25398467
TI  - Treatment of malignant brain edema and increased intracranial pressure after
      stroke.
AB  - OPINION STATEMENT: The management of patients with large territory ischemic
      strokes and the subsequent development of malignant brain edema and increased
      intracranial pressure is a significant challenge in modern neurology and
      neurocritical care. These patients are at high risk of subsequent neurologic
      decline and are best cared for in an intensive care unit or a comprehensive
      stroke center with access to neurosurgical support. Risks include hemorrhagic
      conversion, herniation, poor functional outcome, and death. This review discusses
      recent advances in understanding the pathophysiology of edema formation,
      identifying patients at risk, current management strategies, and emerging
      therapies.

PMID- 25398468
TI  - Visual evoked potentials in a diagnosis of a visual pathway dysfunction of a
      child with an arachnoid cyst.
AB  - PURPOSE: The aim of this case report was to demonstrate the usefulness of the
      flash visual evoked potentials in monitoring the effects of intracranial
      hypertension in a preterm-born child with a congenital arachnoid cyst. METHODS
      AND RESULTS: At baseline, abnormalities were found in the right eye: exotropia
      and lack of foveal fixation. Visual acuity was not achieved. Pupillary responses
      were normal in both eyes. There was no evidence of nystagmus. Flash visual evoked
      potentials were normal and equal in both eyes. When repeated one year later the
      signal had deteriorated in both eyes; the peak times of N2 and P2 had increased.
      The increased VEP latencies were the only ocular signs noted. After referral to
      neurosurgery, intracranial hypertension was found and a shunt was performed.
      CONCLUSIONS: Flash visual evoked potentials may be a valuable test in monitoring
      patients with arachnoid cysts.

PMID- 25398469
TI  - Scaphoid fracture nonunion: correlation of radiographic imaging, proximal
      fragment histologic viability evaluation, and estimation of viability at surgery:
      diagnosis of scaphoid pseudarthrosis.
AB  - PURPOSE: The purpose of this study was to correlate the pre-operative imaging,
      vascularity of the proximal pole, and histology of the proximal pole bone of
      established scaphoid fracture non-union. METHODS: This was a prospective non
      controlled experimental study. Patients were evaluated pre-operatively for
      necrosis of the proximal scaphoid fragment by radiography, computed tomography
      (CT) and magnetic resonance imaging (MRI). Vascular status of the proximal
      scaphoid was determined intra-operatively, demonstrating the presence or absence
      of puncate bone bleeding. Samples were harvested from the proximal scaphoid
      fragment and sent for pathological examination. We determined the association
      between the imaging and intra-operative examination and histological findings.
      RESULTS: We evaluated 19 male patients diagnosed with scaphoid nonunion. CT
      evaluation showed no correlation to scaphoid proximal fragment necrosis. MRI
      showed marked low signal intensity on T1-weighted images that confirmed the
      histological diagnosis of necrosis in the proximal scaphoid fragment in all
      patients. Intra-operative assessment showed that 90% of bones had absence of
      intra-operative puncate bone bleeding, which was confirmed necrosis by
      microscopic examination. CONCLUSIONS: In scaphoid nonunion MRI images with marked
      low signal intensity on T1-weighted images and the absence of intra-operative
      puncate bone bleeding are strong indicatives of osteonecrosis of the proximal
      fragment.

PMID- 25398470
TI  - The influence of the medial meniscus in different conditions on anterior tibial
      translation in the anterior cruciate deficient knee.
AB  - PURPOSE: The purpose of this study was the evaluation of knee laxity in the ACL
      deficient knee with combined meniscal tear, meniscal suture and partial medial
      meniscectomy. METHODS: Kinematics of the intact knee were determined in 18 human
      cadaver specimens in response to a 134-N anterior tibial load (aTT) as well as a
      combined rotatory load of 10 Nm valgus and 4 Nm internal tibial rotation using a
      robotic/universal force moment sensor testing system. The anterior cruciate
      ligament was resected. Subsequently, a vertical bucket-handle medial meniscal
      tear was created followed by a standard meniscus repair using horizontal inside
      out stitches or a partial medial meniscectomy. Knee kinematics were calculated
      following every sub-step. RESULTS: A significant increase of anterior tibial
      translation was found in the ACL-deficient knee compared to the intact knee at 30
      degrees  and 90 degrees  of flexion (p = 0.001; p <= 0.001). Additional tear of
      the medial meniscus significantly increased anterior tibial translation (p =
      0.01). In response to a simulated pivot shift, anterior tibial translation of the
      intact knee did not increase significantly after ACL resection (p = 0.067).
      However, ACL deficiency with an additional medial meniscus tear led to a
      significant increase compared to the intact knee at 0 degrees  of flexion (p =
      0.009). CONCLUSIONS: Additional injury of the medial meniscus increased aTT as
      well as aTT under a combined rotatory load in the ACL-deficient knee whereas
      repair of the meniscus significantly decreased aTT. Therefore, the meniscus
      status does have a significant impact on knee kinematics in the ACL-deficient
      knee. The present biomechanical study further highlights the importance of
      preserving the meniscus especially in patients with additional ACL injuries.

PMID- 25398471
TI  - Outcome of operative treatment of metastatic fractures of the humerus: a
      systematic review of twenty three clinical studies.
AB  - PURPOSE: This systematic review aims to provide an overview of functional outcome
      and complications after surgery for metastatic humerus fractures. METHODS: A
      literature search was performed in September 2013 using the Pubmed, Embase and
      Cochrane database. We included 23 studies reporting on 29 treatment arms:
      intramedullary nailing (19 studies, 596 cases), plate-screw fixation (five
      studies, 150 cases), endoprosthetic reconstruction (three studies, 81 cases), and
      diaphysis prosthesis (two studies, 82 cases), totalling 909 fractures. There were
      414 pathological and 56 impending fractures. In 439 cases the type of fracture
      was not specified. Four studies reported functional outcome. RESULTS: Average
      Musculoskeletal Tumor Society score ranged from 64 to 79 (three studies, 100
      patients) after intramedullary nailing, was 90 (one study, 24 patients) after
      plate-screw fixation, and 73 (one study, 30 patients) after endoprosthetic
      reconstruction. Re-operation rate varied from 0 to 10 % after intramedullary
      nailing (overall 4.4 %), 5-14 % after plate-screw fixation (overall 9.3 %), 14-16
      % after diaphysis prosthesis (overall 14.6 %), and 0-6 % after endoprosthetic
      reconstruction (overall 2.5 %). Systemic complication rate varied between 0 and
      26 % after intramedullary nailing (overall 2.2 %), between 0 and 6 % after plate
      screw fixation (overall 4.8 %), was 0 % after endoprosthetic reconstruction, and
      varied between 0 and 16 % after diaphysis prosthesis (overall 9.7 %).
      CONCLUSIONS: Reported complication rates help surgeons inform their patients and
      could aid in surgical decision making. Functional outcome, pain and quality of
      life were poorly reported. Patient reported outcomes are therefore an important
      direction for future research.

PMID- 25398472
TI  - Thirty-day readmission rate and discharge status following total hip arthroplasty
      using the supercapsular percutaneously-assisted total hip surgical technique.
AB  - PURPOSE: Recent studies have reported nearly 40% of costs associated with a 30
      day episode-of-care for total joint replacements are due to post-discharge
      activities and 81% of those are specifically due to unplanned readmissions and
      discharging patients to post-acute care facilities. The purpose of this study was
      to determine these two key variables for total hip arthroplasty (THA) patients
      implanted using a tissue-sparing surgical technique and to see how these values
      compare to those previously reported in the United States. METHODS: The
      healthcare databases at three institutions were searched for primary THA patients
      implanted using the supercapsular percutaneously-assisted total hip (SuperPath)
      surgical technique between January 2013 and July 2014. Data elements included 30
      day all-cause readmission rate, discharge status, transfusion rate,
      complications, and length of stay (LOS). RESULTS: Data were available for 479
      THAs. The 30-day all-cause readmission rate, transfusion rate, and average LOS
      was 2.3, 3.3%, and 1.6 days, respectively. Over 91% of patients were discharged
      routinely home, 4.1% to skilled nursing facilities, 3.8% to home health care, and
      0.6% to inpatient rehabilitation facilities. Complications included dislocation
      (0.8%), periprosthetic fracture (0.8%), and deep vein thrombosis (0.2 %). There
      were no infections reported. CONCLUSIONS: Patients implanted using this tissue
      sparing technique experienced reduced 30-day all-cause readmission rates (2.3%
      vs. 4.2%) and more were routinely discharged home (91.5% vs. 27.3%) than have
      been previously reported for patients in the United States. Use of this tissue
      sparing technique has the potential to significantly reduce post-discharge costs.

PMID- 25398473
TI  - Does the survival between elderly and very elderly patients with different
      malignant primary bone tumours have no difference?

PMID- 25398474
TI  - Comparative study of radial head resection and prosthetic replacement in surgical
      release of stiff elbows.
AB  - PURPOSE: Elbow trauma can compromise the arc of elbow flexion and forearm
      rotation. This study aimed at comparing the outcomes of radial head resection and
      prosthetic replacement in the surgical release of post traumatic elbow stiffness
      and associated restriction in forearm rotation. METHODS: We retrospectively
      reviewed the data of patients who underwent open arthrolysis with radial head
      resection (n = 15; resection group) or radial head replacement (n = 19;
      replacement group). The pre- and postoperative measurements of the elbow range of
      motion (ROM) were recorded. Elbow function was evaluated by the Broberg and
      Morrey Evaluation System; the Mayo Elbow Performance Index (MEPI); and the
      Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS: Over a
      mean follow-up duration of 22 months, the improvement in the arc of flexion and
      extension was 79 degrees  (range, 45-125 degrees ) and 82 degrees  (range, 10-110
      degrees ), while that in the ROM for forearm rotation was 96 degrees  (range, 40
      150 degrees ) and 102 degrees  (range, 15-150 degrees ) in the resection and
      replacement groups, respectively. There were no significant intergroup
      differences in the elbow ROM measured at the last follow up. The Broberg and
      Morrey, MEPI, and Dash scores in the two groups were comparable. CONCLUSIONS:
      Both resection and prosthetic replacement of the radial head with open
      arthrolysis of post traumatic elbow stiffness were feasible in treating the
      associated restriction of forearm rotation. We recommend that if the elbow is
      stable after complete release, radial head resection is preferable to prosthetic
      replacement because it is technically less demanding.

PMID- 25398475
TI  - MaxSSmap: a GPU program for mapping divergent short reads to genomes with the
      maximum scoring subsequence.
AB  - BACKGROUND: Programs based on hash tables and Burrows-Wheeler are very fast for
      mapping short reads to genomes but have low accuracy in the presence of
      mismatches and gaps. Such reads can be aligned accurately with the Smith-Waterman
      algorithm but it can take hours and days to map millions of reads even for
      bacteria genomes. RESULTS: We introduce a GPU program called MaxSSmap with the
      aim of achieving comparable accuracy to Smith-Waterman but with faster runtimes.
      Similar to most programs MaxSSmap identifies a local region of the genome
      followed by exact alignment. Instead of using hash tables or Burrows-Wheeler in
      the first part, MaxSSmap calculates maximum scoring subsequence score between the
      read and disjoint fragments of the genome in parallel on a GPU and selects the
      highest scoring fragment for exact alignment. We evaluate MaxSSmap's accuracy and
      runtime when mapping simulated Illumina E.coli and human chromosome one reads of
      different lengths and 10% to 30% mismatches with gaps to the E.coli genome and
      human chromosome one. We also demonstrate applications on real data by mapping
      ancient horse DNA reads to modern genomes and unmapped paired reads from NA12878
      in 1000 genomes. CONCLUSIONS: We show that MaxSSmap attains comparable high
      accuracy and low error to fast Smith-Waterman programs yet has much lower
      runtimes. We show that MaxSSmap can map reads rejected by BWA and NextGenMap with
      high accuracy and low error much faster than if Smith-Waterman were used. On
      short read lengths of 36 and 51 both MaxSSmap and Smith-Waterman have lower
      accuracy compared to at higher lengths. On real data MaxSSmap produces many
      alignments with high score and mapping quality that are not given by NextGenMap
      and BWA. The MaxSSmap source code in CUDA and OpenCL is freely available from
      http://www.cs.njit.edu/usman/MaxSSmap.

PMID- 25398476
TI  - [Perioperative aspirin treatment in patients undergoing surgery: Perioperative
      Ischemic Evaluation 2 (POISE-2)].

PMID- 25398477
TI  - Potential determinants of health-care professionals' use of survivorship care
      plans: a qualitative study using the theoretical domains framework.
AB  - BACKGROUND: Survivorship care plans are intended to improve coordination of care
      for the nearly 14 million cancer survivors in the United States. Evidence
      suggests that survivorship care plans (SCPs) have positive outcomes for
      survivors, health-care professionals, and cancer programs, and several high
      profile organizations now recommend SCP use. Nevertheless, SCP use remains
      limited among health-care professionals in United States cancer programs.
      Knowledge of barriers to SCP use is limited in part because extant studies have
      used anecdotal evidence to identify determinants. This study uses the theoretical
      domains framework to identify relevant constructs that are potential determinants
      of SCP use among United States health-care professionals. METHODS: We conducted
      semi-structured interviews to assess the relevance of 12 theoretical domains in
      predicting SCP use among 13 health-care professionals in 7 cancer programs
      throughout the United States with diverse characteristics. Relevant theoretical
      domains were identified through thematic coding of interview transcripts,
      identification of specific beliefs within coded text units, and mapping of
      specific beliefs onto theoretical constructs. RESULTS: We found the following
      theoretical domains (based on specific beliefs) to be potential determinants of
      SCP use: health-care professionals' beliefs about the consequences of SCP use
      (benefit to survivors, health-care professionals, and the system as a whole);
      motivation and goals regarding SCP use (advocating SCP use; extent to which using
      SCPs competed for health-care professionals' time); environmental context and
      resources (whether SCPs were delivered at a dedicated visit and whether a system,
      information technology, and funding facilitated SCP use); and social influences
      (whether using SCPs is an organizational priority, influential people support SCP
      use, and people who could assist with SCP use buy into using SCPs). Specific
      beliefs mapped onto the following psychological constructs: outcome expectancies,
      intrinsic motivation, goal priority, resources, leadership, and team working.
      CONCLUSIONS: Previous studies have explored a limited range of determinants of
      SCP use. Our findings suggest a more comprehensive list of potential determinants
      that could be leveraged to promote SCP use. These results are particularly timely
      as cancer programs face impending SCP use requirements. Future work should
      develop instruments to measure the potential determinants and assess their
      relative influence on SCP use.

PMID- 25398478
TI  - The influence of secondary processing on the structural relaxation dynamics of
      fluticasone propionate.
AB  - This study investigated the structural relaxation of micronized fluticasone
      propionate (FP) under different lagering conditions and its influence on
      aerodynamic particle size distribution (APSD) of binary and tertiary carrier
      based dry powder inhaler (DPI) formulations. Micronized FP was lagered under low
      humidity (LH 25 C, 33% RH [relative humidity]), high humidity (HH 25 degrees C,
      75% RH) for 30, 60, and 90 days, respectively, and high temperature (HT 60
      degrees C, 44% RH) for 14 days. Physicochemical, surface interfacial properties
      via cohesive-adhesive balance (CAB) measurements and amorphous disorder levels of
      the FP samples were characterized. Particle size, surface area, and rugosity
      suggested minimal morphological changes of the lagered FP samples, with the
      exception of the 90-day HH (HH90) sample. HH90 FP samples appeared to undergo
      surface reconstruction with a reduction in surface rugosity. LH and HH lagering
      reduced the levels of amorphous content over 90-day exposure, which influenced
      the CAB measurements with lactose monohydrate and salmeterol xinafoate (SX). CAB
      analysis suggested that LH and HH lagering led to different interfacial
      interactions with lactose monohydrate but an increasing adhesive affinity with
      SX. HT lagering led to no detectable levels of the amorphous disorder, resulting
      in an increase in the adhesive interaction with lactose monohydrate. APSD
      analysis suggested that the fine particle mass of FP and SX was affected by the
      lagering of the FP. In conclusion, environmental conditions during the lagering
      of FP may have a profound effect on physicochemical and interfacial properties as
      well as product performance of binary and tertiary carrier-based DPI
      formulations. 

PMID- 25398479
TI  - Effects of exposure to facial expression variation in face learning and
      recognition.
AB  - Facial expression is a major source of image variation in face images. Linking
      numerous expressions to the same face can be a huge challenge for face learning
      and recognition. It remains largely unknown what level of exposure to this image
      variation is critical for expression-invariant face recognition. We examined this
      issue in a recognition memory task, where the number of facial expressions of
      each face being exposed during a training session was manipulated. Faces were
      either trained with multiple expressions or a single expression, and they were
      later tested in either the same or different expressions. We found that
      recognition performance after learning three emotional expressions had no
      improvement over learning a single emotional expression (Experiments 1 and 2).
      However, learning three emotional expressions improved recognition compared to
      learning a single neutral expression (Experiment 3). These findings reveal both
      the limitation and the benefit of multiple exposures to variations of emotional
      expression in achieving expression-invariant face recognition. The transfer of
      expression training to a new type of expression is likely to depend on a
      relatively extensive level of training and a certain degree of variation across
      the types of expressions. 

PMID- 25398480
TI  - Oscillating glucose and constant high glucose induce endoglin expression in
      endothelial cells: the role of oxidative stress.
AB  - AIM: High glucose-induced oxidative stress has been suggested as one of the
      mediators of endothelial damage in diabetes. The major endothelial protein,
      endoglin, has been found overexpressed in the vessels during pathological
      situations, but little is known about its relation to diabetic vascular
      complications. To clarify the role of endoglin in endothelial injury, we sought
      to determine the effects of high and oscillating glucose on its expression.
      MATERIALS: Furthermore, the activation of the Kruppel-like factor 6 (KLF-6) and
      the hypoxia-inducible factor-1alpha (HIF-1alpha) as possible regulators of
      endoglin expression has been evaluated. The possible role of the oxidative stress
      has been studied evaluating the effects of the antioxidant alpha-lipoic acid
      (ALA) and the cellular antioxidant response mediated by NAD(P)H: quinine-oxido
      reductase-1 (NQO-1) and heme oxygenase-1 (HO-1). RESULTS: Primary HUVECs were
      cultured for 21 days in normal, high and oscillating glucose (5, 25 and 5/25
      mmol/l every 24 h, respectively) with/without ALA. In oscillating and high
      glucose total endoglin, its soluble form (sEng), KLF-6 and HIF-1alpha were
      significantly increased. Simultaneously, the oxidative DNA stress markers 8-OHdG
      and H2A.X were elevated. Moreover, ENG gene transcriptional rate increased during
      glucose exposures concomitantly with increased KLF-6 nuclear translocations. ALA
      significantly reduced all these phenomena. Interestingly, during oscillating and
      chronic high glucose, NQO-1 and HO-1 did not increase, but ALA induced their
      overexpression. CONCLUSIONS: Together, these findings provide novel clue about
      endoglin in the regulation of high glucose-mediated vascular damage in HUVECs and
      the role of oxidative stress in this regulation.

PMID- 25398481
TI  - Characterization of Alu and recombination-associated motifs mediating a large
      homozygous SPG7 gene rearrangement causing hereditary spastic paraplegia.
AB  - Spastic paraplegia type 7 (SPG7) is one of the most common forms of autosomal
      recessive hereditary spastic paraplegia (AR-HSP). Although over 77 different
      mutations have been identified in SPG7 patients, only 9 gross deletions have been
      reported with only a few of them being fully characterized. Here, we present a
      detailed description of a large homozygous intragenic SPG7 gene rearrangement
      involving a 5144-base pair (bp) genomic loss (c. 1450-446_1779 + 746
      delinsAAAGTGCT) encompassing exons 11 to 13, identified in a Spanish AR-HSP
      family. Analysis of the deletion junction sequences revealed that the 5'
      breakpoint of this SPG7 gene deletion was located within highly homologous Alu
      sequences where the 3' breakpoint appears to be flanked by the core crossover
      hotspot instigator (chi)-like sequence (GCTGG). Furthermore, an 8-bp (AAAGTTGCT)
      conserved sequence at the breakpoint junction was identified, suggesting that the
      most likely mechanism for the occurrence of this rearrangement is by Alu
      microhomology and chi-like recombination-associated motif-mediated multiple exon
      deletion. Our results are consistent with non-allelic homologous recombination
      and non-homologous end joining in deletion mutagenesis for the generation of
      rearrangements. This study provides more evidence associating repeated elements
      as a genetic mechanism underlying neurodegenerative disorders, highlighting their
      importance in human diseases.

PMID- 25398482
TI  - Differential Gambling Motivations and Recreational Activity Preferences Among
      Casino Gamblers.
AB  - This study investigated three different types of gamblers (recreational, problem,
      and pathological gamblers) to determine differences in gambling motivations and
      recreational activity preferences among casino gamblers. We collected data from
      600 gamblers recruited in an actual gambling environment inside a major casino in
      South Korea. Findings indicate that motivational factors of escape, sightseeing,
      and winning were significantly different among these three types of gamblers.
      When looking at motivations to visit the casino, pathological gamblers were more
      likely to be motivated by winning, whereas recreational gamblers were more likely
      to be motivated by scenery and culture in the surrounding casino area. Meanwhile,
      the problem gamblers fell between these two groups, indicating higher preferences
      for non-gambling activities than the pathological gamblers. As this study builds
      upon a foundational previous study by Lee et al. (Psychiatry Investig 6(3):141
      149, 2009), the results of this new study were compared with those of the
      previous study to see if new developments within a resort-style casino contribute
      to changes in motivations and recreational activity preferences. 

PMID- 25398483
TI  - Serological and molecular detection of Toscana and other Phleboviruses in
      patients and sandflies in Tunisia.
AB  - BACKGROUND: Our aim is to detect the infection by Toscana virus (TOSV) and other
      Phleboviruses in the sera and cerebro-spinal fluid (CSF) of patients with
      meningitis in Tunisia. We examined various species of phlebotomus present in
      Tunisia to determine whether or not a direct relationship exists between cases of
      meningitis and the viruses circulating in the insect vectors. METHODS: Patients
      with the meningeal syndrome were tested for anti-TOSV IgM and IgG using an
      indirect Enzyme-Linked Immunosorbent Assay (ELISA) and for the presence of TOSV
      and other Phleboviruses using a RT-PCR test. RESULTS: Of 263 patients were tested
      using ELISA of which 12.16% (n = 32/263) were IgM positive for anti TOSV. Of
      these 32 patients, 78% (n = 25/32) were IgG positive. 12.86% (n = 18/140) of the
      CSF samples tested by RT-PCR were positive for the Toscana virus. CONCLUSIONS:
      This study confirms, for the first time, that TOSV is involved in a neurological
      disorder in North Africa. The incidence of this involvement in Tunisia conforms
      with observations made in other Mediterranean countries. Moreover, for the first
      time, a molecular approach was used to detect SFSV in a Tunisian patient
      displaying neurological symptoms.

PMID- 25398485
TI  - Polymyxin B infusion leading to cardiac arrest: a case report and literature
      review.
AB  - We describe a 52-year-old female patient who developed cardiopulmonary arrest due
      to neuromuscular paralysis after initiation of polymyxin B for septicemia caused
      by extended spectrum beta-lactamase-producing Klebsiella pneumoniae. Due to
      emerging antibiotic resistance patterns, use of polymyxins is increasing and an
      understanding of their toxicity is critical. 

PMID- 25398486
TI  - Therapeutic implications of IL-17A blockade in psoriasis.

PMID- 25398487
TI  - IL-17 in psoriasis. The final frontier or just another brick in the wall?

PMID- 25398484
TI  - Current transcriptomics in pig immunity research.
AB  - Swine performance in the face of disease challenge is becoming progressively more
      important. To improve the pig's robustness and resilience against pathogens
      through selection, a better understanding of the genetic and epigenetic factors
      in the immune response is required. This review highlights results from the most
      recent transcriptome research, and the meta-analyses performed, in the context of
      pig immunity. A technological overview is given including wholegenome
      microarrays, immune-specific arrays, small-scale high-throughput expression
      methods, high-density tiling arrays, and next generation sequencing (NGS).
      Although whole genome microarray techniques will remain complementary to NGS for
      some time in domestic species, research will transition to sequencing-based
      methods due to cost-effectiveness and the extra information that such methods
      provide. Furthermore, upcoming high-throughput epigenomic studies, which will add
      greatly to our knowledge concerning the impact of epigenetic modifications on pig
      immune response, are listed in this review. With emphasis on the insights
      obtained from transcriptomic analyses for porcine immunity, we also discuss the
      experimental design in pig immunity research and the value of the newly published
      porcine genome assembly in using the pig as a model for human immune response. We
      conclude by discussing the importance of establishing community standards to
      maximize the possibility of integrative computational analyses, such as was
      clearly beneficial for the human ENCODE project. 

PMID- 25398488
TI  - Pathogenic role of IL-17 in psoriasis and psoriatic arthritis.
AB  - Psoriasis is a chronic inflammatory skin disorder resulting from a complex
      network of cytokines and chemokines produced by various immune cell types and
      tissue cells. Emerging evidence suggests a central role of IL-17 and IL-23/T17
      axis in the pathogenesis of psoriasis, giving a rationale for using IL-17
      blocking agents as therapeutics. Three agents targeting IL-17 signaling are being
      studied in Phase III clinical trials: secukinumab and ixekizumab (IL-17
      neutralizing agents), and brodalumab (IL-17 receptor antagonist). Preliminary
      results are highly promising for all anti-IL17 agents, creating fair expectations
      on this class of agents as the new effective therapeutic approach for the
      treatment of psoriasis. 

PMID- 25398489
TI  - IL-17 and IL-17R: an auspicious therapeutic target for psoriatic disease.
AB  - The continuous discovery of new T cell subpopulations in human autoimmune
      diseases is making the immunopathological network more complex. Th17 cells are
      one such newly identified subset of T cells, characterized by the production of
      signature cytokine IL-17. In last few years, several studies have strongly
      established the regulatory role of Th17 cells and its signature cytokine IL-17 in
      autoimmune diseases including psoriasis, psoriatic arthritis, rheumatoid
      arthritis, inflammatory bowel disease, systemic lupus erythematosus and multiple
      sclerosis. Psoriasis and PsA are immune mediated hyperproliferative diseases,
      affecting skin and joint respectively. Before the discovery of Th17 cells,
      psoriasis and psoriatic diseases were thought to be chiefly Th1 mediated
      diseases; later on IL-17 knockout animal studies as well as human experimental
      data indicate the crucial role of Th17 cells and its signature cytokine IL-17 in
      the pathogenesis of these diseases. In vitro human studies have shown the
      abundance of Th17 cells in the psoriatic plaques. Subsequently our research group
      has extended this observation in psoriatic arthritis and found the abundance of
      CD4+IL-17+ T cells in the synovial fluid and majority of these T cells are of
      memory phenotype (CD4RO+CD45RA-CD11a+). In addition, we showed the significant
      presence of functional IL-17 receptor in synovial fibroblast of psoriatic
      arthritis patients. Considering the strong association of IL-17 and psoriatic
      disease, IL-17 targeted therapy have shown promises in preclinical and clinical
      trials. In this review article, we have discussed the pathogenic role of IL-17 in
      psoriatic disease and summarized the therapeutic efficacy and safety profile of
      different anti IL-17 therapy as an anti-psoriatic agent. 

PMID- 25398490
TI  - IL-17 and infections.
AB  - IL-17 immunity has been shown to be essential for mucocutaneous protection
      against Candida albicans in mice and humans. However, mice with defective IL-17
      immunity display broader susceptibility, as they are also prone to infections
      with diverse infectious agents at various sites. Humans with genetic defects
      affecting their IL-17 immunity usually suffer from chronic mucocutaneous
      candidiasis (CMC): recurrent or persistent infections of the skin, nails, and
      mucosae with C. albicans, with or without other clinical signs. Most patients
      with autosomal dominant (AD) hyper-IgE syndrome (HIES) due to STAT3 deficiency or
      AD STAT1 gain-of-function display impaired IL-17-producing T-cell development,
      and CMC is one of their principal clinical manifestations. Similarly, patients
      with autosomal recessive (AR) autoimmune polyendocrine syndrome type 1 (APS-1)
      caused by AIRE deficiency have high levels of neutralizing autoantibodies against
      IL-17A, IL-17F and/or IL-22 and present CMC as their only infectious disease.
      Finally, CMC is the main clinical phenotype observed in patients with inborn
      errors specifically affecting IL-17 immunity. Indeed, patients with AD IL-17F
      deficiency or AR IL-17RA or ACT1 deficiency display CMC and, to a lesser extent,
      superficial staphylococcal diseases. Candida infection was recently reported in
      psoriasis patients treated with anti-IL-17A antibodies. Careful monitoring for
      CMC is thus important during anti-IL-17 treatment. 

PMID- 25398491
TI  - Role of IL-17 and IL-22 in autoimmunity and cancer.
AB  - The dysregulation of inflammatory cytokines can cause a variety of diseases, such
      as autoimmunity and cancer. Since their identification in 2005, Th17 cells and
      its signature cytokine IL-17, have been implicated in the pathogenesis of
      autoimmune diseases such as psoriasis and rheumatoid arthritis (RA), and
      inflammatory associated cancers such as colorectal carcinoma (CRC). Recently, IL
      22 a Th17 related cytokine has been shown to be pathogenic in psoriasis and RA.
      In this review, we will summarize the biological functions of IL-17 and IL-22,
      their role in autoimmune diseases and briefly review results from clinical trials
      targeting IL-17 or its receptor for the treatment of autoimmune diseases. Next,
      we will discuss pre-clinical and clinical data supporting the rationale of
      targeting other cytokines implicated in the Th17/IL-17 pathway, such as IL-22 and
      IL-23. Finally, we discuss the role of IL-17, and in particularly IL-22 in tumour
      immunity and possible therapeutic interventions. 

PMID- 25398492
TI  - Randomised controlled trials: tests of interaction.

PMID- 25398493
TI  - Establishment of a cellular model to study TrkC-dependent neuritogenesis.
AB  - The rat PC12 cell line has become a widely used research tool for many aspects of
      neurobiology. Nerve growth factor (NGF)-responsive PC12 cells were engineered to
      drive expression of doxycycline (Dox)-induced gene of interest in the Tet-On
      expression system that resulted in obtaining PC12-Tet-On cells. TrkA and TrkC are
      neurotrophin receptors derived from the tropomyosin-related kinase (Trk) family
      of receptor tyrosine kinases. TrkA receptor binds and is activated mainly by NGF,
      while TrkC receptor binds and is activated by neurotrophin 3 (NT3). The purpose
      of this research was to design and describe PC12-based neuronal cell model to
      study TrkC-triggered versus TrkA-triggered neurite outgrowth. The second
      generation tetracycline-responsive promoter (P tight) was used in order to
      provide low basal expression in the absence of Dox and high-level Dox-induced
      expression of TrkC. The main advantage of presented model system is dependence of
      TrkC level on Dox concentration. It also allows to compare activation of
      intracellular signaling proteins and neurite outgrowth following activation of
      TrkA and TrkC receptors by NGF and NT3, respectively, in the context of the same
      quality and quantity of intracellular adaptor proteins, Ras proteins, protein
      kinases and phosphatases, and phospholipase Cgamma1, as a difference in the
      activation of intracellular signaling network by these two distinct although
      related receptor tyrosine kinases is expected. The results of our studies suggest
      that despite slightly weaker activation of ERK1/2 mitogen-activated protein
      kinases, NT3-triggered TrkC seems to provide apparently stronger than NGF
      triggered TrkA signal for neurite elongation in differentiating PC12 cells.

PMID- 25398494
TI  - Why visually impaired older adults often do not receive mental health services:
      the patient's perspective.
AB  - PURPOSE: Older adults with a visual impairment are particularly vulnerable for
      increased depression and anxiety symptoms; however, they tend to underutilise
      mental health services. The present study aims to characterise the perceived need
      for and barriers to use mental health services in visually impaired older adults
      based on Andersen's behavioural model. METHODS: A cross-sectional study in 871
      visually impaired older adults (mean age 73 years) from outpatient low vision
      rehabilitation services was conducted. A multinomial logistic regression analysis
      was performed to assess potential-related factors to perceived need for mental
      health services, measured with the Perceived Need for Care Questionnaire (PNCQ).
      RESULTS: About 35 % of the population had subthreshold depression and/or anxiety,
      and 13 % had a mood and/or anxiety disorder according to the DSM-IV. Almost 34 %
      of the participants with an actual disorder did not receive mental health
      services, even though 57 % perceived to be in need of these services.
      Participants who had more severe depression and/or anxiety, comorbid depression
      and anxiety, no history of major depressive disorder, a lower perceived health
      status and a younger age were more likely to be in need of mental health
      services. Barriers to receive these services were lack of knowledge and self
      reliance. CONCLUSIONS: Findings support the implementation of counselling
      methods, instead of medication, and patient empowerment to reduce an unmet need
      of mental health services in visually impaired older adults, for which extensive
      research is warranted.

PMID- 25398495
TI  - Identifying changes in scores on the EORTC-QLQ-C30 representing a change in
      patients' supportive care needs.
AB  - PURPOSE: Using health-related quality-of-life measures for patient management
      requires knowing what changes in scores require clinical attention. We estimated
      changes on the European Organization for Research and Treatment of Cancer Quality
      of-Life-Questionnaire-Core-30 (EORTC-QLQ-C30), representing important changes by
      comparing to patient-reported changes in supportive care needs. METHODS: This
      secondary analysis used data from 193 newly diagnosed cancer patients (63 %
      breast, 37 % colorectal; mean age 60 years; 20 % male) from 28 Canadian surgical
      practices. Participants completed the Supportive Care Needs Survey-Short Form-34
      (SCNS-SF34) and EORTC-QLQ-C30 at baseline, 3, and 8 weeks. We calculated mean
      changes in EORTC-QLQ-C30 scores associated with improvement, worsening, and no
      change in supportive care needs based on the SCNS-SF34. Mean changes in the EORTC
      QLQ-C30 scores associated with the SCNS-SF34 improved and worsened categories
      were used to estimate clinically important changes, and the 'no change' category
      to estimate insignificant changes. RESULTS: EORTC-QLQ-C30 score changes ranged
      from 6 to 32 points for patients reporting improved supportive care needs;
      statistically significant changes were 10-32 points. EORTC-QLQ-C30 score changes
      ranged from 21-point worsening to 21-point improvement for patients reporting
      worsening supportive care needs; statistically significant changes were 9-21
      points in the hypothesized direction and a 21-point statistically significant
      change in the opposite direction. EORTC-QLQ-C30 score changes ranged from a 1
      point worsening to 16-point improvement for patients reporting stable supportive
      care needs. CONCLUSION: These data suggest 10-point EORTC-QLQ-C30 score changes
      represent changes in supportive care needs. When using the EORTC-QLQ-C30 in
      clinical practice, scores changing >=10 points should be highlighted for clinical
      attention.

PMID- 25398496
TI  - A person-centred analysis of the time-use, daily activities and health-related
      quality of life of Irish school-going late adolescents.
AB  - PURPOSE: The health, well-being and quality of life of the world's 1.2 billion
      adolescents are global priorities. A focus on their patterns or profiles of time
      use and how these relate to health-related quality of life (HRQoL) may help to
      enhance their well-being and address the increasing burden of non-communicable
      diseases in adulthood. This study sought to establish whether distinct profiles
      of adolescent 24-h time-use exist and to examine the relationship of any
      identified profiles to self-reported HRQoL. METHOD: This cross-sectional study
      gathered data from a random sample of 731 adolescents (response rate 52%) from 28
      schools (response rate 76%) across Cork city and county. A person-centred
      approach, latent profile analysis, was used to examine adolescent 24-h time-use
      and relate the identified profiles to HRQoL. RESULTS: Three male profiles
      emerged, namely productive, high leisure and all-rounder. Two female profiles,
      higher study/lower leisure and moderate study/higher leisure, were identified.
      The quantitative and qualitative differences in male and female profiles support
      the gendered nature of adolescent time-use. No unifying trends emerged in the
      analysis of probable responses in the HRQoL domains across profiles. Females in
      the moderate study/higher leisure group were twice as likely to have above
      average global HRQoL. CONCLUSION: Distinct time-use profiles can be identified
      amongst adolescents, but their relationship with HRQoL is complex. Rich mixed
      method research is required to illuminate our understanding of how quantities and
      qualities of time-use shape lifestyle patterns and how these can enhance the
      HRQoL of adolescents in the twenty-first century.

PMID- 25398497
TI  - Not all wheeze is asthma: time for patients to exercise their rights.

PMID- 25398499
TI  - Retracted: Association of ACE I/D gene polymorphism with T2DN susceptibility and
      the risk of T2DM developing into T2DN in a Caucasian population.
AB  - BACKGROUND AND OBJECTIVE: The association of the angiotensin-converting enzyme
      (ACE) insertion/deletion (I/D) gene polymorphism with type-2 diabetic nephropathy
      (T2DN) susceptibility and the risk of type-2 diabetes mellitus (T2DM) developing
      into T2DN in Caucasian populations is still controversial. A meta-analysis was
      performed to evaluate the association of ACE I/D gene polymorphism with T2DN
      susceptibility and the risk of T2DM developing into T2DN in Caucasian
      populations. METHOD: A predefined literature search and selection of eligible
      relevant studies were performed to collect data from electronic databases.
      RESULTS: Sixteen articles were identified for the analysis of the association of
      ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM
      developing into T2DN in Caucasian populations. ACE I/D gene polymorphism was not
      associated with T2DN susceptibility and the risk of patients with T2DM developing
      T2DN in Caucasian populations. Sensitivity analysis according to sample size of
      case (<100 vs. >=100) was also performed, and the results were similar to the non
      sensitivity analysis. CONCLUSIONS: ACE I/D gene polymorphism was not associated
      with T2DN susceptibility and the risk of patients with T2DM developing T2DN in
      Caucasian populations. However, more studies should be performed in the future.

PMID- 25398498
TI  - The Arabidopsis EDR1 protein kinase negatively regulates the ATL1 E3 ubiquitin
      ligase to suppress cell death.
AB  - Loss-of-function mutations in the Arabidopsis thaliana ENHANCED DISEASE
      RESISTANCE1 (EDR1) gene confer enhanced programmed cell death under a variety of
      abiotic and biotic stress conditions. All edr1 mutant phenotypes can be
      suppressed by missense mutations in the KEEP ON GOING gene, which encodes a trans
      Golgi network/early endosome (TGN/EE)-localized E3 ubiquitin ligase. Here, we
      report that EDR1 interacts with a second E3 ubiquitin ligase, ARABIDOPSIS TOXICOS
      EN LEVADURA1 (ATL1), and negatively regulates its activity. Overexpression of
      ATL1 in transgenic Arabidopsis induced severe growth inhibition and patches of
      cell death, while transient overexpression in Nicotiana benthamiana leaves
      induced cell death and tissue collapse. The E3 ligase activity of ATL1 was
      required for both of these processes. Importantly, we found that ATL1 interacts
      with EDR1 on TGN/EE vesicles and that EDR1 suppresses ATL1-mediated cell death in
      N. benthamiana and Arabidopsis. Lastly, knockdown of ATL1 expression suppressed
      cell death phenotypes associated with the edr1 mutant and made Arabidopsis
      hypersusceptible to powdery mildew infection. Taken together, our data indicate
      that ATL1 is a positive regulator of programmed cell death and EDR1 negatively
      regulates ATL1 activity at the TGN/EE and thus controls stress responses
      initiated by ATL1-mediated ubiquitination events. 

PMID- 25398500
TI  - A polymorphism (-455G>A) in the beta-fibrinogen gene is associated with an
      increased risk of cerebral infarction in the Chinese population: A meta-analysis.
AB  - BACKGROUND: Previous studies have investigated the association between a
      polymorphism (-455 G>A) in the beta-fibrinogen gene and the risk of cerebral
      infarction. However, these results are controversial. To shed light on these
      inconclusive findings, we performed a meta-analysis of studies relating the beta
      fibrinogen genetic polymorphism (-455 G>A) to the risk of cerebral infarction.
      METHODS: We identified literature published before July 2013 by searching PubMed,
      EMBASE, ISI Web of Science, the Chinese National Knowledge Infrastructure
      database (CNKI) and the Wanfang database in China and by reviewing the references
      of retrieved articles. We included studies that reported odds ratio (OR) with 95%
      confidence interval (CI) for the association between the beta-fibrinogen genetic
      polymorphism and cerebral infarction risk. Publication bias was tested by a
      funnel plot, and the OR of all studies were combined dependent on the results of
      the heterogeneity tests among the individual studies. The software Review Manager
      (Version 5.2) was used for meta-analysis. RESULTS: Twenty independent case
      control studies containing 9477 subjects were included. Our results showed that
      the -455 G>A polymorphism in the beta-fibrinogen gene was associated with the
      increased risk of cerebral infarction [(AA+GA) vs. GG, OR=1.17, 95%CI: 1.04-1.31,
      p=0.008; A vs. G, OR=1.12, 95%CI: 1.01-1.23, p=0.03] in the Chinese population by
      a meta-analysis. However, we did not find this association in the Caucasian
      population [(AA+GA) vs. GG, OR=0.99, 95%CI: 0.87-1.11, p=0.84; A vs. G, OR=0.97,
      95%CI: 0.84-1.13, p=0.73, respectively]. CONCLUSION: The results of our meta
      analysis indicate that the -455 G>A polymorphism in the beta-fibrinogen gene is a
      susceptibility marker of ischemic cerebral infarction in the Chinese population.

PMID- 25398501
TI  - Simultaneous radical nephroureterectomy and transurethral distal ureter balloon
      occlusion and detachment.
AB  - BACKGROUND: Distal ureter bladder cuff (DUBC) excision is an essential part of
      radical nephroureterectomy (RNU) but there is no agreement on the ideal surgical
      technique to achieve it. We describe a novel technique for endoscopic DUBC
      excision during RNU that complies with the oncological principle of preventing
      spillage of tumor cells, by occluding the distal ureter before its excision,
      while shortening surgical time, and by avoiding repositioning the patient.
      METHODS: Between June 2010 and May 2012, 10 patients underwent simultaneous open
      RNU and transurethral distal ureter balloon occlusion and detachment using a
      flexible cystoscope (f-TUDUBOD) in lumbotomy position. After having ruled out the
      presence of a concomitant bladder tumor, one surgeon used a flexible cystoscope
      to occlude the affected ureter with a 5Fr Fogarty catheter and circumferentially
      incised the orifice until detaching it from the bladder with a boogie electrode
      or a Holmium laser; meanwhile, two other surgeons performed open RNU through a
      lumbotomic approach. Data were compared with those of patients who had previously
      undergone open RNU after TUDUBOD. RESULTS: Mean surgical time for simultaneous
      open RNU and f-TUDUBOD was 113.4+/-29.2 minutes, significantly shorter (P<0.01)
      than that for open RNU after TUDUBOD (154.2+/-26.4 minutes). There were no
      complications. Surgical margins were always negative; at mean follow-up of 31.1
      months, there was no recurrence in the perivesical space and a 20% (2/10) bladder
      recurrence rate comparing favorably with that (23.1%) observed at 30-month follow
      up in patients who had undergone open RNU after TUDUBOD. CONCLUSIONS:
      Simultaneous open RNU and f-TUDUBOD proved to be feasible and to represent a safe
      and effective means of shortening surgical time, with obvious clinical and
      economical benefits.

PMID- 25398502
TI  - Automatic versus manual lymphocyte fixation: impact on dose estimation using the
      cytokinesis-block micronucleus assay.
AB  - The lymphocyte cytokinesis-block micronucleus (CBMN) assay is a biodosemeter for
      the exposure to ionizing radiation. We examined the feasibility to implement a
      fully automated cell harvesting system for binucleate lymphocyte (BN) fixation.
      We compared fully automated versus manual BN fixation and evaluated its relevance
      on the accuracy of dose estimates using the CBMN. First, dose-response curves
      based on X-ray irradiated blood samples of ten healthy donors (0-4 Gy, dose rate
      1.0 Gy/min) were established. BN was either prepared manually or fully
      automatically using the Hanabi cell harvester system PII. Slides were finally
      scored following an automatic or semi-automatic approach using the Metafer4
      platform. The variance was calculated per dose and separately for each of the
      four fixation and scoring combinations. Thereafter, a serial of 16 blood samples
      of unknown exposure doses (0-3.9 Gy X-ray) was analyzed. Employing the four
      fixation and scoring combinations, we compared the number of dose estimates lying
      outside the +/-0.5 Gy interval and the mean absolute difference (MAD) and
      examined sensitivity, specificity and accuracy of doses merged into binary dose
      categories of clinical significance. Irrespective of the fixation procedure, we
      observed at doses <=1.0 Gy about 2-4 times higher median variances for the
      automated scoring procedure over the semi-automated approach (p <= 0.03). The
      lowest median variance was observed for automatic fixation + semi-automated
      scoring (135) which was even 2 times lower relative to manual fixation + semi
      automated scoring (276, p = 0.04). These differences became negligible after
      doses >1.0 Gy. For the automatic fixation procedure, we also observed a tendency
      toward borderline significant higher numbers of dose estimates falling into the
      +/-0.5 Gy interval (25 %, p = 0.08) and lower MAD values (50 %, p = 0.09), which
      was predominantly caused by the accuracy of dose assessment >1.0 Gy. Regarding
      the discrimination of binary dose categories of clinical significance, we
      observed a good agreement of both fixation procedures. The implementation of the
      automatic cell harvesting system considerably reduces the workload and results in
      dose estimates with a tendency of being slightly more accurate as they are after
      a manual fixation. 

PMID- 25398503
TI  - Estrogen alters the profile of the transcriptome in river snail Bellamya
      aeruginosa.
AB  - We evaluated the transcriptome dynamics of the freshwater river snail Bellamya
      aeruginosa exposed to 17beta-estradiol (E2) using the Roche/454 GS-FLX platform.
      In total, 41,869 unigenes, with an average length of 586 bp, representing 36,181
      contigs and 5,688 singlets were obtained. Among them, 18.08, 36.85, and 25.47 %
      matched sequences in the GenBank non-redundant nucleic acid database, non
      redundant protein database, and Swiss protein database, respectively. Annotation
      of the unigenes with gene ontology, and then mapping them to biological pathways,
      revealed large groups of genes related to growth, development, reproduction,
      signal transduction, and defense mechanisms. Significant differences were found
      in gene expression in both liver and testicular tissues between control and E2
      exposed organisms. These changes in gene expression will help in understanding
      the molecular mechanisms of the response to physiological stress in the river
      snail exposed to estrogen, and will facilitate research into biological processes
      and underlying physiological adaptations to xenoestrogen exposure in gastropods. 

PMID- 25398504
TI  - Carotenoid as a sensitive indicator of sub lethal cadmium toxicity in Penaeus
      monodon post larvae.
AB  - The objective of the present study is to evaluate a sensitive indicator of
      cadmium by measuring oxygen consumption and carotenoid concentration in post
      larvae of Penaeus monodon. The post larvae of P. monodon were exposed to 0.12 and
      0.24 mg/L of cadmium in the laboratory for a period of 30 days. These
      concentrations represent 1/10th and 1/5th of 96 h LC50 value for the post larvae.
      Oxygen consumption and carotenoid concentration were measured at 24, 48, 96 h, 10
      and 30 days of cadmium exposure. The results indicated an inhibition of routine
      oxygen consumption in post larvae at different intervals of exposure from 24 h to
      30 days but the effect was statistically significant (P < 05) at 30 days of
      exposure at both sub lethal concentrations, where the inhibition was 38.5 % at
      0.24 mg/L and 21.6 % at 0.12 mg/L. On the other hand, carotenoid concentrations
      increased gradually with increasing period of exposure as well as concentration,
      and this increase was statistically significant (P < 0.05) from 96 h onwards on
      exposure to 0.12 mg/L and from 48 h onwards on exposure to 0.24 mg/L of cadmium,
      with an overall highest increase of 135 %. As carotenoid content is an indicator
      of tissue oxygen, inhibition of routine oxygen consumption might have resulted in
      enhancing the levels of carotenoid. From the present data, it is evident that
      carotenoid concentration can be considered as a sensitive indicator of cadmium
      toxicity than routine oxygen consumption in the post larvae of P. monodon. The
      present investigation is also relevant for environmental monitoring of cadmium in
      coastal waters before it is used for aquaculture. 

PMID- 25398505
TI  - Joint toxicity of tetracycline with copper(II) and cadmium(II) to Vibrio
      fischeri: effect of complexation reaction.
AB  - Co-contamination of antibiotic and heavy metals commonly occurs in the
      environment. Tetracycline (TC), a common antibiotic, can behave as an efficient
      organic ligand to complex with cations. In this paper, the joint toxicity of TC
      with two commonly existing metals, copper(II) and cadmium(II), towards a
      luminescent bacteria, Vibrio fischeri, are investigated. Results showed that
      coexistence of TC and Cu(II) showed a significant antagonistic effect, while TC
      and Cd(II) showed a synergistic effect. The aqueous speciation of TC with two
      metal cations was calculated using a chemical equilibrium software Visual MINTEQ
      and results indicated that a strong complexation exist between TC and Cu(II),
      while much weaker interaction between TC and Cd(II). Traditional joint toxicity
      prediction model based on independent action failed to predict the combined
      toxicity of TC with metals. A new method based on speciation calculation was used
      to evaluate the joint toxicity of ligands and cations. It is assumed that the
      metal-ligand complexes are non-toxic to V. fischeri and the joint toxicity is
      determined by the sum of toxic unit of free metal-ions and free organic ligands.
      It explained the joint toxicity of the mixed systems reasonably well. Meanwhile,
      citric acid (CA) and fulvic acid (FA) were also introduced in this study to
      provide a benchmark comparison with TC. Results showed it is also valid for mixed
      systems of CA and FA with metals except for the Cd-CA mixture. 

PMID- 25398506
TI  - Mandatory and Self-citation; Types, Reasons, Their Benefits and Disadvantages.
AB  - This paper defines and discusses two important types of citations, self-citation
      and mandatory citation, in engineering journals. Citation can be classified in
      three categories: optional; semi-mandatory; and mandatory. There are some
      negative and positive impacts for the authors' paper and journals' reputation if
      mandatory citation of a paper or set of papers is requested. These effects can be
      different based on the recommended papers for citing in the new research.
      Mandatory citation has various types discussed in this paper. Self-citation and
      its reasons and impacts are also discussed in the present study. 

PMID- 25398507
TI  - [Treatment of gunshot fractures of the lower extremity: Part 1: Incidence,
      importance, case numbers, pathophysiology, contamination, principles of emergency
      and first responder treatment].
AB  - Gunshot wounds are rare in Germany and are mostly the result of suicide attempts
      or improper handling of weapons. The resulting injuries involve extensive tissue
      damage and complications which are thus unique and require a differentiated
      approach. As trauma centers may be confronted with gunshot wounds at any time,
      treatment principles must be understood and regularly reevaluated. Due to
      Bundeswehr operations abroad and the treatment of patients from other crisis
      regions a total of 85 gunshot wounds in 64 patients were treated between 2005 and
      2011. In the majority of cases the lower extremities were affected and we were
      able to carry out treatment to preserve the extremities. In this article we
      report on our experiences and the results of treatment of gunshot wounds to the
      lower extremities. This part of the article deals with the epidemiology and
      pathophysiology of gunshot wounds to the lower extremities. By means of an
      evaluation of microbiological findings in a subgroup of patients involved in a
      civil war (n=10), the problem of multidrug resistant pathogen contamination,
      colonization and infection is discussed. In addition to a description of initial
      and emergency treatment of gunshot wounds, measures required for further
      treatment and decontamination are presented. Finally, the results are discussed
      with reference to the literature in this field.

PMID- 25398508
TI  - [Treatment of gunshot fractures of the lower extremity: Part 2: Procedures for
      secondary reconstruction and treatment results].
AB  - BACKGROUND: Gunshot wounds of the lower extremities are always serious injuries,
      especially in cases in which bone is affected. Contamination and extensive tissue
      damage can be life-threatening for the patient and severely affect the function
      of the extremity. Contamination and local infections with multidrug resistant
      pathogens are regularly encountered particularly in casualties evacuated from
      crisis regions. Treatment of this special type of injury, which differs in the
      form and extent from conventional high-energy trauma of the lower extremities,
      usually requires lengthy and extensive therapy algorithms in order to preserve
      the affected extremity. PATIENTS AND METHODS: Based on the results of 34 gunshot
      wounds of the lower extremities which were surgically treated in this department
      between 2005 and 2011, this article reports on procedures used for wound
      management, soft tissue reconstruction and restoration of bone continuity. This
      group included 18 patients with a total of 20 gunshot-related fractures, 40% of
      which affected the lower leg and 35% the thigh. The affected extremities could be
      salvaged in all cases. RESULTS: The therapeutic spectrum required for bone
      reconstruction after soft tissue coverage demonstrated in these case examples
      ranged from conventional osteosynthesis with or without local cancellous bone
      transplant with platelet-rich plasma, to healing in a fixator, bone resection and
      the Masquelet method, distraction osteogenesis using a fixator in order to
      restore continuity and definitive secondary extension using an intramedullary
      skeletal kinetic distractor (ISKD) nail. Out of 15 bullet fractures affecting
      large tubular bones 8 could be healed without any shortening, axis deviation or
      malrotation. In 7 cases definitive shortening by an average of 20 mm (minimum 10
      mm and maximum 40 mm) was necessary. The average treatment time before full
      weight-bearing was achieved within tolerable pain limits was 66 weeks (minimum 4
      weeks and maximum 267 weeks). Secondary osteitis and osteomyelitis following
      primary restoration was detected in only one case. CONCLUSION: These results show
      that the treatment of gunshot wounds of the lower extremities is time-consuming
      and extensive and requires the complete spectrum of modern trauma surgery.
      Despite the high risk of complications during treatment it is possible and
      feasible to apply procedures that preserve the extremities.

PMID- 25398509
TI  - [Gunshot and stab wounds in Germany--epidemiology and outcome: analysis from the
      TraumaRegister DGU(r)].
AB  - BACKGROUND: The management of gunshot wounds is a rare challenge for trauma
      surgeons in Germany and Central Europe as a result of the low incidence of this
      type of trauma. Penetrating injuries occur with an incidence of 5% in Germany.
      They are caused by gunshots or more commonly by knives or other objects, for
      example during accidents. Since even the number of patients who are treated at
      level 1 trauma centres is limited by the low incidence, the objective of this
      study was to assess the epidemiology and outcome of gunshot and stab wounds in
      Germany. MATERIAL AND METHODS: Since 2009, the trauma registry of the German
      Trauma Society (TraumaRegister DGU(r)) has been used to assess not only whether a
      trauma was penetrating but also whether it was caused by a gunshot or a stabbing.
      On the basis of this registry, we identified relevant cases and defined the
      observation period. Data were taken from the standard documentation forms that
      participating German hospitals completed between 2009 and 2011. We did not
      specify exclusion criteria in order to obtain as comprehensive a picture as
      possible of the trauma entities investigated in this study. As a result of the
      high incidence of gunshot wounds to the head and the implications of this type of
      injury for the entire group, a subgroup of patients without head injuries was
      analysed. RESULTS: From 2009 to 2011, there were 305 patients with gunshot wounds
      and 871 patients with stab wounds. The high proportion of suicide-related gunshot
      wounds to the head resulted in a cumulative mortality rate of 39.7%. Stab wounds
      were associated with a lower mortality rate (6.2%). Every fourth patient with a
      gunshot or stab wound presented with haemorrhagic shock, which was considerably
      more frequently seen during the prehospital phase than during the inhospital
      phase of patient management. Of the patients with gunshot wounds, 26.9% required
      transfusions. This percentage was three times higher than that for patients with
      blunt trauma. CONCLUSION: In Germany, gunshot and stab wounds have a low
      incidence and are mostly caused by violent crime or attempted suicide. Depending
      on the site of injury, they have a high mortality and are often associated with
      major haemorrhage. As a result of the low incidence of these types of trauma,
      further data and analyses are required which can provide the basis for an
      evaluation of the long-term quality of the management of patients with stab or
      gunshot wounds.

PMID- 25398510
TI  - [Fractures of the distal radius].
AB  - The most prevalent fractures managed by trauma surgeons are those involving the
      distal radius. The injury occurs in two peaks of prevalence: the first peak
      around the age of 10 years and the second peak around the age of 60 years. Distal
      radius fracture management requires sensitive diagnostics and classification. The
      objectives of treatment are the reconstruction of a pain-free unlimited durable
      functioning of the wrist and avoidance of typical fracture complications. Non
      operative conservative management is generally employed for stable non-displaced
      fractures of the distal radius with the expectation of a good functional outcome.
      Unstable comminuted fractures with intra-articular and extra-articular fragment
      zones are initially set in a closed operation and finally by osteosynthesis. An
      armament of surgical implants is available for instable fractures requiring
      fixation. Palmar locked plate osteosynthesis has been established in recent years
      as the gold standard for operative management of distal radius fractures. Complex
      Working Group on Osteosynthesis (AO) classification type 3 fractures require
      extensive preoperative diagnostics to identify and treat typical associated
      injuries around the wrist. 

PMID- 25398511
TI  - [Fractures of the distal radius: operative technique of fixed-angle palmar plates
      for extension type fractures].

PMID- 25398512
TI  - [Implementation of a department of plastic surgery in a university clinic for
      trauma surgery].
AB  - BACKGROUND: Since May 2012 plastic surgery for trauma patients at the University
      Hospital Leipzig is provided by an autonomous department. OBJECTIVES: This study
      analyzed the effect of plastic surgery on the changes in diagnosis-related groups
      (DRG) at a clinic for trauma surgery. MATERIALS AND METHODS: Within the first 2
      years 37 patients (29 male and 8 female of which 38 were inpatient cases) were
      admitted to the clinic for trauma surgery and additionally received plastic
      surgery treatment. The appropriate DRG assignment as well as associated codes and
      revenues were recorded and compared with and without plastic surgery. RESULTS: A
      total of 261 operations were performed on these patients of which 71 were
      performed by the department of plastic surgery. The mean revenue was 22,156.44
      EUR+/-20,578.22 EUR with a mean cost weighting of 7.2+/-6.7. Excluding plastic
      surgery treatment the mean revenue was 19,378.44 EUR+/-20,688.40 EUR and the mean
      cost weighting was 6.3+/-6.7. Thus, additional proceeds by the plastic surgery
      treatment were 2778.00 EUR+/-3857.01 EUR per case. The mean increase of the cost
      weighting was 0.9+/-1.3. A change of the DRG grouping occurred in 20 out of 38
      cases treated. The mean length of stay (LoS) was 40.2+/-26.6 days. In the first
      year this was 17.9+/-22.4 days more than the mean national LoS of the appropriate
      DRG and 10.9+/-19.3 days in the second year. This means an average cost reduction
      of 4774.59 EUR per case. CONCLUSION: The implementation of a department for
      plastic surgery increased the revenues. Additional profits should be achieved by
      process enhancement and not by prolonged LoS.

PMID- 25398513
TI  - [Combined gunshot injuries of the heart and lungs].
AB  - The authors present a case report of a 38-year-old man who suffered combined
      gunshot injuries of the heart and lungs from a small caliber gun. The gunshot
      resulted in combined injuries of a penetrating wound of the left lung, the right
      heart chambers and the right lung which were successfully managed despite a delay
      in surgery of several hours by pledget sutures of the heart wounds, wedge
      resection of the lingula and right lower lung lobectomy performed via a clamshell
      thoracotomy. 

PMID- 25398514
TI  - Carcinogenic polycyclic aromatic hydrocarbons induce CYP1A1 in human cells via a
      p53-dependent mechanism.
AB  - The tumour suppressor gene TP53 is mutated in more than 50 % of human tumours,
      making it one of the most important cancer genes. We have investigated the role
      of TP53 in cytochrome P450 (CYP)-mediated metabolic activation of three
      polycyclic aromatic hydrocarbons (PAHs) in a panel of isogenic colorectal HCT116
      cells with differing TP53 status. Cells that were TP53(+/+), TP53(+/-), TP53(-/
      ), TP53(R248W/+) or TP53(R248W/-) were treated with benzo[a]pyrene (BaP),
      dibenz[a,h]anthracene and dibenzo[a,l]pyrene, and the formation of DNA adducts
      was measured by (32)P-postlabelling analysis. Each PAH formed significantly
      higher DNA adduct levels in TP53(+/+) cells than in the other cell lines. There
      were also significantly lower levels of PAH metabolites in the culture media of
      these other cell lines. Bypass of the need for metabolic activation by treating
      cells with the corresponding reactive PAH-diol-epoxide metabolites resulted in
      similar adduct levels in all cell lines, which confirms that the influence of p53
      is on the metabolism of the parent PAHs. Western blotting showed that CYP1A1
      protein expression was induced to much greater extent in TP53(+/+) cells than in
      the other cell lines. CYP1A1 is inducible via the aryl hydrocarbon receptor
      (AHR), but we did not find that expression of AHR was dependent on p53; rather,
      we found that BaP-induced CYP1A1 expression was regulated through p53 binding to
      a p53 response element in the CYP1A1 promoter region, thereby enhancing its
      transcription. This study demonstrates a new pathway for CYP1A1 induction by
      environmental PAHs and reveals an emerging role for p53 in xenobiotic metabolism.

PMID- 25398515
TI  - Variation analysis of six HCV viral load assays using low viremic HCV samples in
      the range of the clinical decision points for HCV protease inhibitors.
AB  - In the range of clinical decision points for response-guided therapy of HCV,
      there is still insufficient data concerning the conformity of quantification
      results obtained by different assays and their correlation with the HPS/CTM v2
      assay which was used for initial clinical studies. In a head-to-head comparison,
      assay accuracy and detection rates of six quantitative assays [artus HCV QS-RGQ,
      COBAS Ampliprep/COBAS TaqMan HCV v1/v2, High Pure System/COBAS TaqMan (HPS),
      RealTime HCV, and Versant HCV1.0] were assessed by measuring WHO and PEI
      standards at dilution steps near clinical decision points. Detection rates and
      mean differences between assays were evaluated by analyzing twenty clinical
      samples at 10, 100, and 1,000 IU/mL. Ten replicates from specimens with different
      HCV genotypes were used to analyze pan-genotypic intra-assay variation. At <= 25
      IU/mL, RealTime demonstrated the highest detection rates. With 0.1 log difference
      when testing clinical samples, results obtained from the Versant and RealTime
      assays matched best with results from HPS. Mean difference analysis across all
      assay results revealed wide differences between 0.01 and 0.75 log IU/mL. RealTime
      showed the lowest intra-assay variation across genotypes 1-4 (25, 100, 1,000
      IU/mL). There are substantial analytical differences between viral load assays
      clinicians should be aware of. These variations may have impact on clinical
      decisions for patients on HCV triple therapy and may argue for assay-specific
      decision points equivalent to reference values established in studies using HPS.
      A comparison of quantification is recommended prior to a switch of assays during
      ongoing therapy.

PMID- 25398516
TI  - Stereotactic body radiation therapy (SBRT) for prostate cancer in men with large
      prostates (>=50 cm(3)).
AB  - BACKGROUND: Patients with large prostate volumes have been shown to have higher
      rates of genitourinary and gastrointestinal toxicities after conventional
      radiation therapy for prostate cancer. The efficacy and toxicity of stereotactic
      body radiation therapy (SBRT), which delivers fewer high-dose fractions of
      radiation treatment, is unknown for large prostate volume prostate cancer
      patients. We report our early experience using SBRT for localized prostate cancer
      in patients with large prostate volumes. METHODS: 57 patients with prostate
      volumes >=50 cm(3) prior to treatment with SBRT for localized prostate carcinoma
      and with a minimum follow up of two years were included in this retrospective
      review of prospectively collected data. Treatment was delivered using Cyberknife
      (Accuray) with doses of 35-36.25 Gy in 5 fractions. Biochemical control was
      assessed using the Phoenix definition. Toxicities were scored using the CTCAE
      v.4. Quality of life was assessed using the American Urological Association (AUA)
      Symptom Score and the Expanded Prostate Cancer Index Composite (EPIC)-26.
      RESULTS: 57 patients (23 low-, 25 intermediate- and 9 high-risk according to the
      D'Amico classification) at a median age of 69 years (range, 54-83 years) received
      SBRT with a median follow-up of 2.9 years. The median prostate size was 62.9
      cm(3) (range 50-138.7 cm(3)). 33.3% of patients received ADT. The median pre
      treatment prostate-specific antigen (PSA) was 6.5 ng/ml and decreased to a median
      PSA of 0.4 ng/ml by 2 years (p <0.0001). A mean baseline AUA symptom score of 7.5
      significantly increased to 13 at 1 month (p = 0.001) and returned to baseline by
      3 months (p = 0.21). 23% of patients experienced a late transient urinary symptom
      flare in the first two years following treatment. Mean baseline EPIC bowel scores
      of 95.8 decreased to 78.1 at 1 month (p <0.0001), but subsequently improved to
      93.5 three months (p = 0.08). The 2-year actuarial incidence rates of GU and GI
      toxicity >= grade 2 were 49.1% and 1.8%, respectively. Two patients (3.5%)
      experienced grade 3 urinary toxicity, and no patient experienced grade 3
      gastrointestinal toxicity. CONCLUSIONS: SBRT for clinically localized prostate
      cancer was well tolerated in men with large prostate volumes.

PMID- 25398517
TI  - Association of Race, Ethnicity and Language with Participation in Mental Health
      Research Among Adult Patients in Primary Care.
AB  - Racial and ethnic minorities remain underrepresented in clinical psychiatric
      research, but the reasons are not fully understood and may vary widely between
      minority groups. We used the Z-test of independent proportions and binary
      logistic regression to examine the relationship between race, ethnicity or
      primary language and participation in screening as well as interest in further
      research participation among primary care patients being screened for a
      depression study. Minorities were less likely than non-Hispanic Whites to
      complete the initial screening survey. Latinos and Blacks were more likely to
      agree to be contacted for research than non-Hispanic Whites. Among Latinos,
      primary language was associated with willingness to be contacted for research.
      Associations between research participation and race, ethnicity and language are
      complex and vary across different enrollment steps. Future research should
      consider stages of the research enrollment process separately to better
      understand barriers and identify targets for intervention. 

PMID- 25398518
TI  - The Association of Afro-Caribbean Immigrants' Feelings of Disconnection from the
      Community with the Metabolic Syndrome.
AB  - Many immigrants can feel like outsiders in their adopted country. The objective
      of this study was to determine if psychosocial stress associated with feelings of
      disconnection from the community is associated with the metabolic syndrome (Met
      S) among Afro-Caribbean immigrants. The frequency of the Met-S, based on
      International Diabetes Federation criteria, was determined for a population-based
      sample of 406 English-speaking Afro-Caribbean immigrants ages twenty and older in
      the Virgin Islands of the United States (USVI). Feelings of disconnection were
      assess with Roger's Life Attitude Inventory. Logistic regression analyses showed
      that a high level of disconnection was significantly associated with the Met-S
      [Odds Ratio = 1.64 (95% CI 1.10-2.44)] after adjusting for conventional risk
      factors and for body mass index. Afro-Caribbean immigrants in the USVI who
      express a high level of disconnection from the community have an increased risk
      for the Met-S.

PMID- 25398520
TI  - Increasing the value of research in palliative care.

PMID- 25398519
TI  - Application of reduced-port laparoscopic total gastrectomy in gastric cancer
      preserving the pancreas and spleen.
AB  - BACKGROUND: The feasibility of using reduced-port laparoscopic total gastrectomy
      (RPLTG) for the treatment of gastric cancer remains unclear. This study aimed to
      address the potentially important advantages of this surgical technique. METHODS:
      Between April 2002 and February 2014, 90 patients underwent laparoscopy-assisted
      total gastrectomies, performed by a single surgeon. Of these, 45 patients
      underwent RPLTG and 45 patients underwent conventional laparoscopy-assisted total
      gastrectomy (CLATG). Short-term outcomes were compared to evaluate the
      feasibility of RPLTG for gastric cancer. RESULTS: There were several significant
      differences between the RPLTG and CLATG groups in short-term outcomes: the mean
      total operation durations were significantly longer in the RPLTG group (319.0
      min) than in the CLATG group (259.0 min). However, the mean volume of blood loss,
      the degree of lymph node dissection, and the number of dissected lymph nodes did
      not differ between the two groups. CONCLUSIONS: We have shown that RPLTG could be
      an acceptable and satisfactory procedure for the treatment of gastric cancer
      requiring total gastrectomy for surgeons sufficiently experienced in CLATG.

PMID- 25398521
TI  - Prevalence and indications for bladder catheterization on a palliative care unit:
      a prospective, observational study.

PMID- 25398523
TI  - [Rapid improvement in vision and visual field after olfactory groove meningioma
      operation].
AB  - This article reports the case of a 46-year-old female patient with a large
      olfactory groove meningioma (56 * 60 * 52 mm). Postoperatively, the patient
      rapidly experienced a significant improvement in vision and visual field, which
      initially was greatly impaired (initial vision 0.2 and circular impairment of the
      visual field of the left eye). The meningioma was resected by a frontal,
      osteoplastic craniotomy. Even on the sixth postoperative day, the vision and the
      visual field had completely recovered. An operative approach is indicated in
      large meningiomas targeting a complete resection.

PMID- 25398524
TI  - Leptin differentially increases sympathetic nerve activity and its baroreflex
      regulation in female rats: role of oestrogen.
AB  - Obesity and hypertension are commonly associated, and activation of the
      sympathetic nervous system is considered to be a major contributor, at least in
      part due to the central actions of leptin. However, while leptin increases
      sympathetic nerve activity (SNA) in males, whether leptin is equally effective in
      females is unknown. Here, we show that intracerebroventricular (i.c.v.) leptin
      increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and
      RSNA in alpha-chloralose anaesthetized female rats, but only during pro-oestrus.
      In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic
      SNA (SSNA) and heart rate (HR) in rats in both the pro-oestrus and dioestrus
      states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in
      males and pro-oestrus females; however, i.c.v. leptin increased mean arterial
      pressure (MAP) only in males. Leptin did not alter LSNA or HR in ovariectomized
      rats, but its effects were normalized with 4 days of oestrogen treatment.
      Bilateral nanoinjection of SHU9119 into the paraventricular nucleus of the
      hypothalamus (PVN), to block alpha-melanocyte-stimulating hormone (alpha-MSH)
      type 3 and 4 receptors, decreased LSNA in leptin-treated pro-oestrus but not
      dioestrus rats. Unlike leptin, i.c.v. insulin infusion increased basal and
      baroreflex control of LSNA and HR similarly in pro-oestrus and dioestrus rats;
      these responses did not differ from those in male rats. We conclude that, in
      female rats, leptin's stimulatory effects on SNA are differentially enhanced by
      oestrogen, at least in part via an increase in alpha-MSH activity in the PVN.
      These data further suggest that the actions of leptin and insulin to increase the
      activity of various sympathetic nerves occur via different neuronal pathways or
      cellular mechanisms. These results may explain the poor correlation in females of
      SNA with adiposity, or of MAP with leptin.

PMID- 25398525
TI  - Phosphatidylinositol 4,5-bisphosphate degradation inhibits the Na+/bicarbonate
      cotransporter NBCe1-B and -C variants expressed in Xenopus oocytes.
AB  - KEY POINTS: We previously reported that the phospholipid phosphatidylinositol 4,5
      bisphosphate (PIP2 ) directly stimulates heterologously expressed electrogenic
      Na(+)/bicarbonate cotransporter NBCe1-A in an excised macropatch from the Xenopus
      oocyte, and indirectly stimulates NBCe1-B and -C in the intact oocyte primarily
      through inositol 1,4,5-trisphosphate/Ca(2+). In the current study, we expand on a
      previous observation that PIP2 may also directly stimulate NBCe1 in the intact
      oocyte. In this study on oocytes, we co-expressed either NBCe1-B or -C and a
      voltage-sensitive phosphatase (VSP), which depletes PIP2 without changing
      inositol 1,4,5-trisphosphate, and monitored NBCe1-mediated currents with the two
      electrode voltage-clamp technique or pHi changes using Vm/pH-sensitive
      microelectrodes. Activating VSP inhibited NBCe1-B and -C outward currents and
      NBCe1-mediated pHi increases, and changes in NBCe1 activity paralleled changes in
      surface PIP2. This study is a quantitative assessment of PIP2 itself as a
      regulator of NBCe1-B and -C in the intact cell, and represents the first use of
      VSP to characterize the PIP2 sensitivity of a transporter. These data combined
      with our previous work demonstrate that NBCe1-B and -C are regulated by two PIP2
      mediated signalling pathways. Specifically, a decrease in PIP2 per se can inhibit
      NBCe1, whereas hydrolysis of PIP2 to inositol 1,4,5-trisphosphate/Ca(2+) can
      stimulate the transporter. ABSTRACT: The electrogenic Na(+)/bicarbonate
      cotransporter (NBCe1) of the Slc4 gene family is a powerful regulator of
      intracellular pH (pHi) and extracellular pH (pHo), and contributes to solute
      reabsorption and secretion in many epithelia. Using Xenopus laevis oocytes
      expressing NBCe1 variants, we have previously reported that the phospholipid
      phosphatidylinositol 4,5-bisphosphate (PIP2) directly stimulates NBCe1-A in an
      excised macropatch, and indirectly stimulates NBCe1-B and -C in the intact oocyte
      primarily through inositol 1,4,5-trisphosphate (InsP3)/Ca(2+). In the current
      study, we used the two-electrode voltage-clamp technique alone or in combination
      with pH/voltage-sensitive microelectrodes or confocal fluorescence imaging of
      plasma membrane PIP2 to characterize the PIP2 sensitivity of NBCe1-B and -C in
      whole oocytes by co-expressing a voltage-sensitive phosphatase (VSP) that
      decreases PIP2 and bypasses the InsP3/Ca(2+) pathway. An oocyte depolarization
      that activated VSP only transiently stimulated the NBCe1-B/C current, consistent
      with an initial rapid depolarization-induced NBCe1 activation, and then a
      subsequent slower VSP-mediated NBCe1 inhibition. Upon repolarization, the NBCe1
      current decreased, and then slowly recovered with an exponential time course that
      paralleled PIP2 resynthesis as measured with a PIP2-sensitive fluorophore and
      confocal imaging. A subthreshold depolarization that minimally activated VSP
      caused a more sustained increase in NBCe1 current, and did not lead to an
      exponential current recovery following repolarization. Similar results were
      obtained with oocytes expressing a catalytically dead VSP mutant at all
      depolarized potentials. Depleting endoplasmic reticulum Ca(2+) did not inhibit
      the NBCe1 current recovery following repolarization from VSP activation,
      demonstrating that changes in InsP3/Ca(2+) were not responsible. This study
      demonstrates for the first time that depleting PIP2 per se inhibits NBCe1
      activity. The data in conjunction with previous findings implicate a dual PIP2
      regulatory pathway for NBCe1 involving both PIP2 itself and generated
      InsP3/Ca(2+).

PMID- 25398526
TI  - Effect of uraemia on endothelial cell damage is mediated by the integrin linked
      kinase pathway.
AB  - KEY POINTS: Patients with chronic kidney disease have a higher risk of developing
      cardiovascular diseases than the general population. Their vascular endothelium
      is dysfunctional, among other things, because it is permanently exposed to
      uraemic toxins, several of which have poor clearance by conventional dialysis.
      Recent studies have demonstrated the important role of integrin-linked kinase
      (ILK) in the maintenance of endothelial integrity and in this study we
      investigate the involvement of ILK in the mechanism underlying vascular
      endothelial damage that occurs in uraemia. For the first time, we demonstrate the
      implication of ILK in the protection against endothelial cell damage (inhibition
      of proliferation, toxicity, oxidative stress and programed cell death) induced by
      uraemic serum from chronic kidney disease patients and uraemic toxins. This
      molecular mechanism may have clinical relevance because it highlights the
      importance of maintaining high levels of ILK activity to help preserve
      endothelial integrity, at least in early stages of chronic kidney disease.
      ABSTRACT: Patients with chronic kidney disease (CKD) have a higher risk of
      developing cardiovascular diseases. Their vascular endothelium is dysfunctional,
      among other things, because it is permanently exposed to uraemic toxins, several
      of which, mostly protein-bound compounds such as indoxyl sulfate (IS) and p
      cresyl sulphate, having poor clearance by conventional dialysis, induce
      endothelial toxicity. However, the molecular mechanism by which uraemic toxins
      regulate early stages of endothelial dysfunction remains unclear. Recent studies
      have demonstrated the important role of integrin-linked kinase (ILK) in the
      maintenance of endothelial integrity. In this study, we investigate the
      involvement of ILK in the mechanism underlying vascular endothelial damage that
      occurs in uraemia. First, we show that incubation of EA.hy926 cells with human
      uraemic serum from CKD patients upregulates ILK activity. This ILK activation
      also occurs when the cells are exposed to IS (25-100 MUg ml(-1)), p-cresol (10
      100 MUg ml(-1)) or both combined, compared to human serum control. Next, we
      observed that high doses of both toxins together induce a slight decrease in cell
      proliferation and increase apoptosis and reactive oxygen species production.
      Interestingly, these toxic effects displayed a strong increase when the ILK
      protein is knocked down by small interfering RNA, even at low doses of uraemic
      toxins. Abrogation of AKT has demonstrated the ILK/AKT signalling pathway
      involved in these processes. This study has demonstrated the implication of ILK
      in the protection against endothelial cell damage induced by uraemic toxins, a
      molecular mechanism that could play a protective role in the early stages of
      endothelial dysfunction observed in uraemic patients.

PMID- 25398527
TI  - Stimulus-specific effects of noradrenaline in auditory cortex: implications for
      the discrimination of communication sounds.
AB  - KEY POINTS: Many studies have described the action of Noradrenaline (NA) on the
      properties of cortical receptive fields, but none has assessed how NA affects the
      discrimination abilities of cortical cells between natural stimuli. In the
      present study, we compared the consequences of NA topical application on spectro
      temporal receptive fields (STRFs) and responses to communication sounds in the
      primary auditory cortex. NA application reduced the STRFs (an effect replicated
      by the alpha1 agonist Phenylephrine) but did not change, on average, the
      responses to communication sounds. For cells exhibiting increased evoked
      responses during NA application, the discrimination abilities were enhanced as
      quantified by Mutual Information. The changes induced by NA on parameters
      extracted from the STRFs and from responses to communication sounds were not
      related. ABSTRACT: The alterations exerted by neuromodulators on neuronal
      selectivity have been the topic of a vast literature in the visual,
      somatosensory, auditory and olfactory cortices. However, very few studies have
      investigated to what extent the effects observed when testing these functional
      properties with artificial stimuli can be transferred to responses evoked by
      natural stimuli. Here, we tested the effect of noradrenaline (NA) application on
      the responses to pure tones and communication sounds in the guinea-pig primary
      auditory cortex. When pure tones were used to assess the spectro-temporal
      receptive field (STRF) of cortical cells, NA triggered a transient reduction of
      the STRFs in both the spectral and the temporal domain, an effect replicated by
      the alpha1 agonist phenylephrine whereas alpha2 and beta agonists induced STRF
      expansion. When tested with communication sounds, NA application did not produce
      significant effects on the firing rate and spike timing reliability, despite the
      fact that alpha1, alpha2 and beta agonists by themselves had significant effects
      on these measures. However, the cells whose evoked responses were increased by NA
      application displayed enhanced discriminative abilities. These cells had
      initially smaller STRFs than the rest of the population. A principal component
      analysis revealed that the variations of parameters extracted from the STRF and
      those extracted from the responses to natural stimuli were not correlated. These
      results suggest that probing the action of neuromodulators on cortical cells with
      artificial stimuli does not allow us to predict their action on responses to
      natural stimuli.

PMID- 25398528
TI  - Divergent muscle sympathetic responses to dynamic leg exercise in heart failure
      and age-matched healthy subjects.
AB  - KEY POINTS: People with diminished ventricular contraction who develop heart
      failure have higher sympathetic nerve firing rates at rest compared with healthy
      individuals of a similar age and this is associated with less exercise capacity.
      During handgrip exercise, sympathetic nerve activity to muscle is higher in
      patients with heart failure but the response to leg exercise is unknown because
      its recording requires stillness. We measured sympathetic activity from one leg
      while the other leg cycled at a moderate level and observed a decrease in nerve
      firing rate in healthy subjects but an increase in subjects with heart failure.
      Because these nerves release noradrenaline, which can restrict muscle blood flow,
      this observation helps explain the limited exercise capacity of patients with
      heart failure. Lower nerve traffic during exercise was associated with greater
      peak oxygen uptake, suggesting that if exercise training attenuated sympathetic
      outflow functional capacity in heart failure would improve. ABSTRACT: The reflex
      fibular muscle sympathetic nerve (MSNA) response to dynamic handgrip exercise is
      elicited at a lower threshold in heart failure with reduced ejection fraction
      (HFrEF). The present aim was to test the hypothesis that the contralateral MSNA
      response to mild to moderate dynamic one-legged exercise is augmented in HFrEF
      relative to age- and sex-matched controls. Heart rate (HR), blood pressure and
      MSNA were recorded in 16 patients with HFrEF (left ventricular ejection fraction
      = 31 +/- 2%; age 62 +/- 3 years, mean +/- SE) and 13 healthy control subjects (56
      +/- 2 years) before and during 2 min of upright one-legged unloaded cycling
      followed by 2 min at 50% of peak oxygen uptake (VO2,peak). Resting HR and blood
      pressure were similar between groups whereas MSNA burst frequency was higher
      (50.0 +/- 2.0 vs. 42.3 +/- 2.7 bursts min(-1), P = 0.03) and VO2,peak lower (18.0
      +/- 2.0 vs. 32.6 +/- 2.8 ml kg(-1) min(-1), P < 0.001) in HFrEF. Exercise
      increased HR (P < 0.001) with no group difference (P = 0.1). MSNA burst frequency
      decreased during mild to moderate dynamic exercise in the healthy controls but
      increased in HFrEF (-5.5 +/- 2.0 vs. 6.9 +/- 1.8 bursts min(-1), P < 0.001).
      Exercise capacity correlated inversely with MSNA burst frequency at 50% VO2,peak
      (n = 29; r = -0.64; P < 0.001). At the same relative workload, one-legged dynamic
      exercise elicited a fall in MSNA burst frequency in healthy subjects but
      sympathoexcitation in HFrEF, a divergence probably reflecting between-group
      differences in reflexes engaged by cycling. This finding, coupled with an inverse
      relationship between MSNA burst frequency during loaded cycling and subjects'
      VO2,peak, is consistent with a neurogenic determinant of exercise capacity in
      HFrEF.

PMID- 25398529
TI  - Macro-micro imaging of cardiac-neural circuits in co-cultures from normal and
      diseased hearts.
AB  - The autonomic nervous system plays an important role in the modulation of normal
      cardiac rhythm, but is also implicated in modulating the heart's susceptibility
      to re-entrant ventricular and atrial arrhythmias. The mechanisms by which the
      autonomic nervous system is pro-arrhythmic or anti-arrhythmic is multifaceted and
      varies for different types of arrhythmia and their cardiac substrates. Despite
      decades of research in this area, fundamental questions related to how neuron
      density and spatial organization modulate cardiac wave dynamics remain
      unanswered. These questions may be ill-posed in intact tissues where the activity
      of individual cells is often experimentally inaccessible. Development of
      simplified biological models that would allow us to better understand the
      influence of neural activation on cardiac activity can be beneficial. This
      Symposium Review summarizes the development of in vitro cardiomyocyte cell
      culture models of re-entrant activity, as well as challenges associated with
      extending these models to include the effects of neural activation. 

PMID- 25398531
TI  - Virtual leak channels modulate firing dynamics and synaptic integration in rat
      sympathetic neurons: implications for ganglionic transmission in vivo.
AB  - KEY POINTS: The synaptic organization of paravertebral sympathetic ganglia
      enables them to relay activity from the spinal cord to the periphery and thereby
      control autonomic functions, including blood pressure and body temperature. The
      present experiments were done to reconcile conflicting observations in tissue
      culture, intact isolated ganglia and living animals. By recording intracellularly
      from dissociated neurons and intact ganglia, we found that when electrode damage
      makes cells leaky it could profoundly distort cellular excitability and the
      integration of synaptic potentials. The experiments relied on the dynamic clamp
      method, which allows the creation of virtual ion channels by injecting current
      into a cell based upon a mathematical model and using rapid feedback between the
      model and cell. The results support the hypothesis that sympathetic ganglia can
      produce a 2.4-fold amplification of presynaptic activity. This could aid
      understanding of the neural hyperactivity that is believed to drive high blood
      pressure in some patients. ABSTRACT: The excitability of rat sympathetic neurons
      and integration of nicotinic EPSPs were compared in primary cell culture and in
      the acutely isolated intact superior cervical ganglion using whole cell patch
      electrode recordings. When repetitive firing was classified by Hodgkin's criteria
      in cultured cells, 18% displayed tonic class 1 excitability, 36% displayed
      adapting class 2 excitability and 46% displayed phasic class 3 excitability. In
      the intact ganglion, 71% of cells were class 1 and 29% were class 2. This
      diverges from microelectrode reports that nearly 100% of superior cervical
      ganglion neurons show phasic class 3 firing. The hypothesis that the disparity
      between patch and microelectrode data arises from a shunt conductance was tested
      using the dynamic clamp in cell culture. Non-depolarizing shunts of 3-10 nS
      converted cells from classes 1 and 2 to class 3 dynamics with current-voltage
      relations that replicated microelectrode data. Primary and secondary EPSPs
      recorded from the intact superior cervical ganglion were modelled as virtual
      synapses in cell culture using the dynamic clamp. Stimulating sympathetic neurons
      with virtual synaptic activity, designed to replicate in vivo recordings of EPSPs
      in muscle vasoconstrictor neurons, produced a 2.4-fold amplification of
      presynaptic activity. This gain in postsynaptic output did not differ between
      neurons displaying the three classes of excitability. Mimicry of microelectrode
      damage by virtual leak channels reduced and eventually obliterated synaptic gain
      by inhibiting summation of subthreshold EPSPs. These results provide a framework
      for interpreting sympathetic activity recorded from intact animals and support
      the hypothesis that paravertebral ganglia function as activity-dependent
      amplifiers of spinal output from preganglionic circuitry.

PMID- 25398533
TI  - Survival of AIDS patients in Sao Paulo-Brazil in the pre- and post-HAART eras: a
      cohort study.
AB  - BACKGROUND: Brazil was the first middle-income country to provide free and
      universal access to AIDS treatment. Understanding the impact of this policy is
      key to promote ongoing improvement of current intervention strategies. The aim of
      this study was to compare mortality rates and survival in a cohort of AIDS
      patients before and after the introduction of antiretrovirals (ARV) and to
      investigate predictors of survival. METHODS: A retrospective cohort study of AIDS
      patients aged 13 years or more living in the city of Sao Paulo was conducted. All
      patients were recruited from an STD/HIV outpatient clinic between 1988 and 2003
      and followed up until 2005. We estimated AIDS mortality rates in person-years
      (py) and carried out a survival analysis using the Kaplan-Meier method. The Cox
      proportional hazards model was used to assess predictors of survival in AIDS
      patients. RESULTS: The study cohort comprised 6,594 patients. The yearly mean
      mortality rates were 17.6, 23.2, and 7.8 per 1,000 py for the study periods 1988
      1993, 1994-1996, and 1997-2003, respectively. Median survival time was 13.4 and
      22.3 months for patients entering the study in the first and second study periods
      and survival time was 108 months or more in 72% of those entering the study
      during 1997-2003. Factors independently associated with shorter survival
      included: AIDS diagnosis during the 1994-1996 (HR 2.0) and 1988-1993 (HR 3.2)
      periods; 50 years of age or more (HR 2.0); exposure category of injection drug
      users (IDU) (HR 1.5); 8 years of schooling or less (HR 1.4); no schooling (HR
      2.1); and CD4+ counts between 350 and 500 cells/mm(3) (HR 1.2) and less than 350
      cells/mm(3) at AIDS diagnosis (HR 1.3). CONCLUSIONS: The study showed a strong
      impact following the introduction of HAART in 1996 with decreased AIDS mortality,
      increased survival rates, and benefits with early introduction of HAART. However,
      some groups of patients were less likely to benefit from the new drug regimens.
      Public policies promoting health equity create an enabling environment helping
      AIDS control programs in developing countries to achieve their goals as
      effectively as in developed countries.

PMID- 25398532
TI  - Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals.
AB  - Ca(2+)-activated chloride channels (CaCCs) regulate numerous physiological
      processes including epithelial transport, smooth muscle contraction and sensory
      processing. Anoctamin-1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell
      types, yet our understanding of the mechanisms of ANO1 activation and regulation
      are only beginning to emerge. Ca(2+) sensitivity of ANO1 is rather low and at
      negative membrane potentials the channel requires several micromoles of
      intracellular Ca(2+) for activation. However, global Ca(2+) levels in cells
      rarely reach such levels and, therefore, there must be mechanisms that focus
      intracellular Ca(2+) transients towards the ANO1 channels. Recent findings indeed
      indicate that ANO1 channels often co-localize with sources of intracellular
      Ca(2+) signals. Interestingly, it appears that in many cell types ANO1 is
      particularly tightly coupled to the Ca(2+) release sites of the intracellular
      Ca(2+) stores. Such preferential coupling may represent a general mechanism of
      ANO1 activation in native tissues.

PMID- 25398534
TI  - Clinical trials of Ebola therapies to begin in December.

PMID- 25398535
TI  - The Bcl-2 family: structures, interactions and targets for drug discovery.
AB  - Two phylogenetically and structurally distinct groups of proteins regulate stress
      induced intrinsic apoptosis, the programmed disassembly of cells. Together they
      form the B cell lymphoma-2 (Bcl-2) family. Bcl-2 proteins appeared early in
      metazoan evolution and are identified by the presence of up to four short
      conserved sequence blocks known as Bcl-2 homology (BH) motifs, or domains. The
      simple BH3-only proteins bear only a BH3-motif and are intrinsically disordered
      proteins and antagonize or activate the other group, the multi-motif Bcl-2
      proteins that have up to four BH motifs, BH1-BH4. Multi-motif Bcl-2 proteins are
      either pro-survival or pro-apoptotic in action and have remarkably similar alpha
      helical bundle structures that provide a binding groove formed from the BH1, BH2,
      and BH3-motifs for their BH3-bearing antagonists. In mammals a network of
      interactions between Bcl-2 members regulates mitochondrial outer membrane
      permeability (MOMP) and efflux of cytochrome c and other death inducing factors
      from mitochondria to initiate the apoptotic caspase cascade, but the molecular
      events leading to MOMP are uncertain. Dysregulation of the Bcl-2 family occurs in
      many diseases and pathogenic viruses have assimilated pro-survival Bcl-2 proteins
      to evade immune responses. Their role in disease has made the Bcl-2 family the
      focus of drug design attempts and clinical trials are showing promise for 'BH3
      mimics', drugs that mimic the ability of BH3-only proteins to neutralize selected
      pro-survival proteins to induce cell death in tumor cells. This review focuses on
      the structural biology of Bcl-2 family proteins, their interactions and attempts
      to harness them as targets for drug design. 

PMID- 25398536
TI  - Activation and assembly of the inflammasomes through conserved protein domain
      families.
AB  - Inflammasomes are oligomeric protein complexes assembled through interactions
      among the death domain superfamily members, in particular the CARD and PYD
      domains. Recent progress has shed lights on how the ASC PYD can polymerize to
      form filaments using multiple domain:domain interfaces, and how the caspase4 CARD
      can recognize LPS to activate the non-classical inflammasome pathway.
      Comprehensive understanding of the molecular mechanisms of inflammasome
      activation and assembly require more extensive structural and biophysical
      dissection of the inflammasome components and complexes, in particular additional
      CARD or PYD filaments. Because of the variations in death domain structures and
      complexes observed so far, future work will undoubtedly shed lights on the
      mechanisms of inflammasome assembly as well as more surprises on the versatile
      structure and function of the death domain superfamily. 

PMID- 25398537
TI  - Tandem DEDs and CARDs suggest novel mechanisms of signaling complex assembly.
AB  - Apoptosis is an important process to maintain cellular homeostasis. Deregulated
      apoptosis has linked to a number of diseases, such as inflammatory diseases,
      neurodegenerative disorder, and cancers. A major signaling complex in the death
      receptor signaling pathway leading to apoptosis is death-induced signaling
      complex (DISC), which is regulated mainly by death effector domain (DED)
      containing proteins. There are seven DED-containing proteins in human, including
      FADD, c-FLIP, caspase-8, caspase-10, DEDD, DEDD2, and PEA-15. The main players in
      DISC formation employ tandem DEDs for regulating signaling complex formation. The
      regulatory mechanism of signaling complex formation is important and yet remains
      unclear. Interestingly, three caspase recruitment domain (CARD)-containing
      members, which belong to the same DD superfamily as DED-containing proteins, also
      contains similar tandem CARDs. Recent structural studies have shown that tandem
      CARDs are essential for the formation of a helical signaling complex. This review
      summarizes recent structural studies on DED-containing proteins and especially
      discusses the studies on tandem DEDs and tandem CARDs, which suggest new
      mechanisms of signaling complex assembly. 

PMID- 25398538
TI  - Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset
      sensitivity and potential effect of TP53 Arg72Pro polymorphism.
AB  - We tested apoptosis levels in in vitro irradiated T-lymphocytes from breast
      cancer (BC) patients with radiotherapy-induced late effects. Previous results
      reported in the literature were revised. We also examined the effect of TP53
      Arg72Pro polymorphism on irradiation-induced apoptosis (IA). Twenty BC patients,
      ten with fibrosis and/or telangiectasias and ten matched controls with no late
      reactions, were selected from those receiving radiotherapy between 1993 and 2007.
      All patients were followed-up at least 6 years after radiotherapy. Using the
      combination of both CD3 and CD8 antibodies the in vitro IA was measured in CD3,
      CD8 and CD4 T-lymphocytes, and CD8 natural killer lymphocytes (CD8 NK) by flow
      cytometry. The TP53 Arg72Pro genotype was determined by sequencing. Patients with
      late radiotherapy toxicity showed less IA for all T-lymphocytes except for the
      CD8 NK. CD8 NK showed the highest spontaneous apoptosis and the lowest IA. IA in
      patients with toxicity appears to be lower than the control patients only in TP53
      Arg/Arg patients (P = 0.077). This difference was not present in patients
      carrying at least one Pro allele (P = 0.8266). Our data indicate that late side
      effects induced by radiotherapy of BC are associated to low levels of IA. CD8 NK
      cells have a different response to in vitro irradiation compared to CD8 T
      lymphocytes. It would be advisable to distinguish the CD8 NK lymphocytes from the
      pool of CD8+ lymphocytes in IA assays using CD8+ cells. Our data suggest that the
      72Pro TP53 allele may influence the IA of patients with radiotherapy toxicity.

PMID- 25398539
TI  - Oxidative stress by monosodium urate crystals promotes renal cell apoptosis
      through mitochondrial caspase-dependent pathway in human embryonic kidney 293
      cells: mechanism for urate-induced nephropathy.
AB  - The aim of this study is to clarify the effect of oxidative stress on monosodium
      urate (MSU)-mediated apoptosis of renal cells. Quantitative real-time polymerase
      chain reaction and immunoblotting for Bcl-2, caspase-9, caspase-3, iNOS,
      cyclooxygenase-2 (COX-2), interleukin-1beta (IL-1beta), IL-18, TNF receptor
      associated factor-6 (TRAF-6), and mitogen-activated protein kinases were
      performed on human embryonic kidney 293 (HEK293) cells, which were stimulated by
      MSU crystals. Fluorescence-activated cell sorting was performed using annexin V
      for assessment of apoptosis. Reactive oxygen species (ROS) were measured. IL
      1beta siRNA was used for blocking IL-1beta expression. MSU crystals promoted ROS,
      iNOS, and COX-2 expression and also increased TRAF-6 and IL-1beta expression in
      HEK293 cells, which was inhibited by an antioxidant ascorbic acid. Caspase
      dependent renal cell apoptosis was induced through attenuation of Bcl-2 and
      enhanced caspase-3 and caspase-9 expression by MSU crystals, which was
      significantly reversed by ascorbic acid and transfection of IL-1beta siRNA to
      HEK293 cells. Ascorbic acid inhibited phosphorylation of extracellular signal
      regulated kinase and Jun N-terminal protein kinase stimulated by MSU crystals.
      ROS accumulation and iNOS and COX-2 mRNA expression by MSU crystals was also
      suppressed by transfection with IL-1beta siRNA. Oxidative stress generated by MSU
      crystals promotes renal apoptosis through the mitochondrial caspase-dependent
      apoptosis pathway. 

PMID- 25398540
TI  - RIP1-dependent Bid cleavage mediates TNFalpha-induced but Caspase-3-independent
      cell death in L929 fibroblastoma cells.
AB  - L929 fibroblastoma cells (L929-A) and L929 fibrosarcoma cells (L929-N) are
      different cell lines that are commonly used to study the cytotoxicity of tumor
      necrosis factor alpha (TNFalpha). TNFalpha has been reported to induce necrosis
      in both of these cell lines. However, comparing the TNFalpha-induced cell death
      in these two cell lines, we found that, unlike the L929-N cells that show typical
      RIP3-dependent necrosis, TNFalpha-induced cell death in L929-A cells is pan
      caspase inhibitor Z-VAD-FMK (Z-VAD)-sensitive, which does not depend on RIP3. We
      also confirmed that the cell death signal in the L929-A cells was initiated
      through cytosol-preassembled ripoptosome and that the knockdown of either Caspase
      8 or RIP1 protein blocked cell death. Compared with the L929-N cells, the L929-A
      cell line had lower levels of constitutive and inducible TNFalpha autocrine
      production, and the pan-caspase inhibitors Z-VAD or Q-VD did not kill the L929-A
      cells as they affect the L929-N cells. Moreover, the L929-A cells expressed less
      RIP3 protein than the L929-N cells; therefore, TNFalpha failed to induce RIP3
      dependent necroptosis. In addition, the ripoptosome-mediated cell death signal
      was transduced to the mitochondria through Caspase-8-mediated and RIP1 kinase
      activity-dependent Bid cleavage. The RIP1 kinase inhibitor Necrostatin-1 (Nec-1)
      or Caspase-8 knockdown completely blocked Bid cleavage, and the knockdown of Bid
      or Bax/Bak prevented TNFalpha-induced cell death in the L929-A cells. Although
      the activation of Bax/Bak decreased the mitochondrial membrane potential, the
      levels of mitochondrial intermembrane space proteins, including cytochrome-c (cyt
      C) and Smac, declined, and western blotting and immunofluorescence staining
      analysis did not determine whether these proteins were redistributed to the
      cytosol. In addition, the mitochondrial outer membrane protein Tom20 was also
      reduced, indicating that the reduced mitochondria proteins may be induced by the
      reduced mitochondria numbers. No efficient cyt-C release was observed; therefore,
      the limited activation and cleavage of downstream caspases, including Caspase-9,
      Caspase-7, Caspase-6 and Caspase-3, was insufficient to kill the cells. The
      Caspase-9, Caspase-6 and Caspase-3/7 inhibitors or Caspase-9 and -3 knockdown
      also failed to block cell death, and the overexpression of Bcl-2 also did not
      abrogate cell death. Moreover, the dead cells showed necrotic-like but not
      apoptotic characteristics under transmission electronmicroscopy, and these
      features were significantly different from mitochondrial apoptosis, indicating
      that the effector caspases were not the executioners of cell death. These new
      discoveries show that TNFalpha-induced cell death in L929-A cells is different
      than typical RIP3-dependent necrosis and Caspase-8/Caspase-3-mediated apoptosis.
      These results highlight that caution is necessary when using different L929 cells
      as a model to investigate TNFalpha-induced cell death. 

PMID- 25398541
TI  - Ruthenium (II) complexes interact with human serum albumin and induce apoptosis
      of tumor cells.
AB  - The interaction of ruthenium (II) complex [Ru(bpy)2(mal)](2+) (RBM) and
      [Ru(phen)2(mal)](2+) (RPM) (bpy = 2, 2-bipyridine, phen = 1,10-phenanthroline,
      mal = malonyl carboxylate) with human serum albumin (HSA) has been investigated
      by using fluorescence, UV absorption and circular dichroism (CD) spectroscopy
      approaches. A strong fluorescence quenching reaction of complexes to HSA was
      observed and the quenching mechanism was suggested as static quenching according
      to the Stern-Volmer (S-V) equation. The number of binding sites n and observed
      binding constant Kb was measured by fluorescence quenching method. The
      thermodynamic parameters DeltaH, DeltaS, and DeltaG at different temperatures
      were calculated and the results indicate the binding reaction is mainly entropy
      driven and Vander Waals force played a major role in the reaction. The result of
      CD showed that the secondary structure of HSA molecules was changed in the
      presence of the ruthenium (II) complexes. Furthermore, the cell viability of
      ruthenium (II) complexes was evaluated by MTT and complex RPM has shown
      significant higher anticancer potency than RBM against all the cell lines
      screened. RPM showed a significant antitumor activity through induction of
      apoptosis in A549 cells. 

PMID- 25398542
TI  - Analysis of the content of cadmium and zinc in parts of the human hip joint.
AB  - Cadmium is an element with proven direct and indirect toxic effects on bones.
      Zinc affects the content of cadmium in the human body. These elements show
      antagonistic interactions. The aim of the research was to determine the levels of
      cadmium and zinc in the hip joint tissues and interactions between these
      elements. The study group consisted of 91 subjects, 66 women and 25 men. The
      tissues were obtained intraoperatively during hip endoprosthetic surgery. The
      levels of cadmium and zinc were assayed by the atomic absorption
      spectrophotometry (AAS) method. The analysis of the content of cadmium and zinc
      in different parts of the hip joint, i.e., articular cartilage, cortical bone,
      and cancellous bone of the femoral head as well as the articular capsule and a
      fragment of the cancellous bone taken from the intertrochanteric region of the
      femoral bone showed significant differences. The cancellous bone was found to
      have the highest potential to accumulate the elements studied, whereas part of
      the articular capsule the lowest. Higher levels of cadmium and zinc were observed
      in samples obtained from men. Patients with bone fractures had higher cadmium
      content than those with osteoarthritis. The study on the content of cadmium and
      zinc in the tissues of the hip joint is one of the primary research
      biomonitoring. 

PMID- 25398543
TI  - Combined effects of Lanthanum(III) and elevated Ultraviolet-B radiation on root
      nitrogen nutrient in soybean seedlings.
AB  - Rare earth element pollution and elevated ultraviolet-B (UV-B) radiation occur
      simultaneously in some regions, but the combined effects of these two factors on
      plants have not attracted enough attention. Nitrogen nutrient is vital to plant
      growth. In this study, the combined effects of lanthanum(III) and elevated UV-B
      radiation on nitrate reduction and ammonia assimilation in soybean (Glycine max
      L.) roots were investigated. Treatment with 0.08 mmol L(-1) La(III) did not
      change the effects of elevated UV-B radiation on nitrate reductase (NR), nitrite
      reductase (NiR), glutamine synthetase (GS), glutamate synthase (GOGAT), glutamate
      dehydrogenase (GDH), nitrate, ammonium, amino acids, or soluble protein in the
      roots. Treatment with 0.24 mmol L(-1) La(III) and elevated UV-B radiation
      synergistically decreased the NR, NiR, GS, and GOGAT activities as well as the
      nitrate, amino acid, and soluble protein levels, except for the GDH activity and
      ammonium content. Combined treatment with 1.20 mmol L(-1) La(III) and elevated UV
      B radiation produced severely deleterious effects on all test indices, and these
      effects were stronger than those induced by La(III) or elevated UV-B radiation
      treatment alone. Following the withdrawal of La(III) and elevated UV-B radiation,
      all test indices for the combined treatments with 0.08/0.24 mmol L(-1) La(III)
      and elevated UV-B radiation recovered to a certain extent, but they could not
      recover for treatments with 1.20 mmol L(-1) La(III) and elevated UV-B radiation.
      In summary, combined treatment with La(III) and elevated UV-B radiation seriously
      affected nitrogen nutrition in soybean roots through the inhibition of nitrate
      reduction and ammonia assimilation. 

PMID- 25398544
TI  - Cyclooxygenase-1 as the main source of proinflammatory factors after sodium
      orthovanadate treatment.
AB  - Vanadium is a metal present in air pollution. Its compounds may have both
      anticancer and carcinogenic properties. Vanadium compounds are tested in
      treatment of diabetes and cancer. An important research direction aimed at better
      understanding of the mechanisms of action of the vanadium compounds is a more
      detailed insight into their impact on inflammatory reactions. The aim of this
      study was to examine the effect of micromolar concentrations of sodium
      orthovanadate, Na3VO4, on the activity and expression of cyclooxygenases: COX-1
      and COX-2. PMA-activated THP-1 macrophages were incubated in vitro for 48 h with
      micromolar concentrations of sodium orthovanadate. As shown by an ELISA assay,
      sodium orthovanadate increases the quantity of prostaglandin E2 being released
      into the medium in a dose-dependent manner as well as impacts the quantity of the
      stable metabolite of thromboxane A2: thromboxane B2. The use of a COX-2
      inhibitor, NS-398, revealed that this effect was independent of changes in the
      activity of COX-2. Western blotting analysis showed that sodium orthovanadate
      increased the expression of COX-2 when used with NS-398. Quantitative real-time
      PCR measurements of mRNA levels of genes PTGS1 and PTGS2 revealed no effect of
      the tested vanadium compound on the levels of analyzed transcripts. 

PMID- 25398545
TI  - FRIZZY PANICLE drives supernumerary spikelets in bread wheat.
AB  - Bread wheat (Triticum aestivum) inflorescences, or spikes, are characteristically
      unbranched and normally bear one spikelet per rachis node. Wheat mutants on which
      supernumerary spikelets (SSs) develop are particularly useful resources for work
      towards understanding the genetic mechanisms underlying wheat inflorescence
      architecture and, ultimately, yield components. Here, we report the
      characterization of genetically unrelated mutants leading to the identification
      of the wheat FRIZZY PANICLE (FZP) gene, encoding a member of the
      APETALA2/Ethylene Response Factor transcription factor family, which drives the
      SS trait in bread wheat. Structural and functional characterization of the three
      wheat FZP homoeologous genes (WFZP) revealed that coding mutations of WFZP-D
      cause the SS phenotype, with the most severe effect when WFZP-D lesions are
      combined with a frameshift mutation in WFZP-A. We provide WFZP-based resources
      that may be useful for genetic manipulations with the aim of improving bread
      wheat yield by increasing grain number. 

PMID- 25398547
TI  - Trans and interesterified fat and palm oil during the pregnancy and lactation
      period inhibit the central anorexigenic action of insulin in adult male rat
      offspring.
AB  - Palm oil and interesterified fat have been used to replace partially hydrogenated
      fats, rich in trans isomers, in processed foods. This study investigated whether
      the maternal consumption of normolipidic diets containing these lipids affects
      the insulin receptor and Akt/protein kinase B (PKB) contents in the hypothalamus
      and the hypophagic effect of centrally administered insulin in 3-month-old male
      offspring. At 90 days, the intracerebroventricular injection of insulin decreased
      24-h feeding in control rats but not in the palm, interesterified or trans
      groups. The palm group exhibited increases in the insulin receptor content of 64
      and 69 % compared to the control and trans groups, respectively. However, the
      quantifications of PKB did not differ significantly across groups. We conclude
      that the intake of trans fatty acid substitutes during the early perinatal period
      affects food intake regulation in response to centrally administered insulin in
      the young adult offspring; however, the underlying mechanisms remain unclear.

PMID- 25398548
TI  - Using hyper-spectral indices to detect soil phosphorus concentration for various
      land use patterns.
AB  - The management of nonpoint source pollution requires accurate information
      regarding soil phosphorus concentrations for different land use patterns. The use
      of remotely sensed information provides an important opportunity for such
      studies, and the previous studies showed that soil phosphorus shows no clear
      spectral response feature, while the phosphorus concentrations can be indirectly
      detected from the normalised difference vegetation indices (NDVI). Therefore,
      this study uses an optimised index in the RED and near-infrared (NIR) wavelengths
      to estimate total phosphorus and Olsen-P concentrations. The prediction accuracy
      is not entirely satisfactory with respect to a mixed land use dataset in which
      the determination coefficient was maintained at approximately 0.6, with
      particularly poor performance obtained for forest land group. However, the
      prediction accuracy increases markedly with the separation of samples into broad
      land use categories, even the R(2) was exceeded 0.8 for tea plantation group. The
      soil phosphorus prediction effect showed obvious variance for different land use
      patterns, which was related to vegetation growth conditions and critical soil
      properties including soil organic matter and mechanical composition.

PMID- 25398549
TI  - Five Describing Factors of Dyslexia.
AB  - Two subtypes of dyslexia (phonological, visual) have been under debate in various
      studies. However, the number of symptoms of dyslexia described in the literature
      exceeds the number of subtypes, and underlying relations remain unclear. We
      investigated underlying cognitive features of dyslexia with exploratory and
      confirmatory factor analyses. A sample of 446 students (63 with dyslexia)
      completed a large test battery and a large questionnaire. Five factors were found
      in both the test battery and the questionnaire. These 10 factors loaded on 5
      latent factors (spelling, phonology, short-term memory, rhyme/confusion, and
      whole-word processing/complexity), which explained 60% of total variance. Three
      analyses supported the validity of these factors. A confirmatory factor analysis
      fit with a solution of five factors (RMSEA = .03). Those with dyslexia differed
      from those without dyslexia on all factors. A combination of five factors
      provided reliable predictions of dyslexia and nondyslexia (accuracy >90%). We
      also looked for factorial deficits on an individual level to construct subtypes
      of dyslexia, but found varying profiles. We concluded that a multiple cognitive
      deficit model of dyslexia is supported, whereas the existence of subtypes remains
      unclear. We discussed the results in relation to advanced compensation strategies
      of students, measures of intelligence, and various correlations within groups of
      those with and without dyslexia.

PMID- 25398550
TI  - Retroperitoneoscopic Adrenalectomy in Obese Patients: Is It Suitable?
AB  - BACKGROUND: The aim of this study was to evaluate the suitability of posterior
      retroperitoneoscopic adrenalectomy for patients with morbid obesity. METHODS:
      This retrospective clinical cohort study included patients who underwent elective
      posterior retroperitoneoscopic adrenalectomy. Intraoperative (operative time,
      blood loss, intraoperative complications, conversion rate) and postoperative
      (hospital stay, morbidity, mortality) parameters were compared between the two
      study subgroups: obese (body mass index [BMI] >=30 kg/m(2)) and non-obese
      patients (BMI <30 kg/m(2)). RESULTS: A total of 137 subsequent patients were
      enrolled in the study (41 obese and 96 non-obese patients). Mean tumour size was
      5.2 +/- 2.2 cm; aldosteronism and incidentaloma were the most frequent
      indications. Operative time was significantly longer (87 vs. 65 min; P = 0.0006)
      in obese patients. There was no difference in operative blood loss. One
      conversion was necessary. Overall, the 30-day postoperative morbidity was
      significantly higher in obese patients (26.8 vs. 11.5 %; P = 0.025). The hospital
      stay was significantly longer in obese patients (3.1 vs. 2.5 days; P = 0.003).
      CONCLUSIONS: Dorsal retroperitoneoscopic adrenalectomy can be safely performed in
      morbidly obese patients, maintaining the advantages of minimally invasive
      surgery. Avoiding an abdominal approach is beneficial for patients. There is a
      more favourable postoperative course, shorter hospital stay, better cosmetic
      outcome and quicker recovery with dorsal retroperitoneoscopic adrenalectomy. The
      prolonged operative time, longer hospital stay and higher risk of postoperative
      complications that occurred in obese patients were acceptable in light of the
      generally higher risk associated with surgeries performed in obese patients.

PMID- 25398552
TI  - Standardizing or tailoring bariatric surgery.

PMID- 25398551
TI  - Early experience with customized, meal-triggered gastric electrical stimulation
      in obese patients.
AB  - BACKGROUND: We report our initial gastric electrical stimulation experience using
      the abiliti(r) system for the treatment of obese patients followed for 1 year.
      METHOD: Between March 2011 and June 2013, 27 obese patients (BMI 30 to 46
      kg/m(2)) were enrolled in a prospective open label study and implanted with a
      gastric stimulator. The patients were provided with nutritional support, and
      sensor-based behavioral feedback. RESULTS: At 12 months, percent excess weight
      loss (%EWL) obtained was 49.3 +/- 19.2 % with no significant differences between
      gender or age sub-groups. The %EWL data were segmented into two groups according
      to BMI 30-40 kg/m(2) patients (obesity grade I and II) and BMI >40 kg/m(2), with
      the results of weight loss being significantly higher for the lower BMI group
      (59.1 +/- 19.5 vs. 46.7 +/- 13.4, respectively, p < 0.01). One subject requested
      to have his device explanted, and the minor postoperative adverse events were
      resolved without hospital admission. All patients experienced early satiety and
      reduced their intake. CONCLUSIONS: After 12 months of follow-up, gastric
      electrical stimulation treatment appears to be a safe and effective option for
      weight loss in obese subjects. Long-term follow-up and further studies are
      warranted.

PMID- 25398553
TI  - From prescriptions to drug use periods - things to notice.
AB  - BACKGROUND: Electronic prescription registers provide a vast data source for
      pharmacoepidemiological research. Prescriptions as such are not suitable for all
      research purposes; e.g., studying concurrent use of different drugs or adverse
      drug events during current use. For those purposes, data on dispensed
      prescriptions needs to be transformed to periods of drug use. METHODS: We used
      3,828,292 dispensed prescriptions claimed between 1 January 2002 and 31 December
      2009 for 28,093 persons with Alzheimer's disease. Examples of drug use histories
      are presented to discuss different aspects that should be noticed when using
      register-based data consisting of drug purchases. RESULTS: There is no simple
      method for correctly transforming dispensed prescriptions to periods of drug use
      that is usable for all drugs and drug users. Fixed assumptions of daily dose (in
      defined daily doses, tablets or other units) and fixed time windows should be
      used with caution and adjusted for different drug use patterns. CONCLUSIONS: We
      recommend that when transforming prescription drug purchases to drug use periods
      personal dose, purchasing pattern and other behavioral differences between
      patients should be taken into account.

PMID- 25398554
TI  - Mouse cerebral magnetic resonance imaging fails to visualize brain volume changes
      after experimental subarachnoid hemorrhage.
AB  - BACKGROUND: Brain atrophy after subarachnoid hemorrhage (SAH) has been detected
      in humans and might serve as a functional read-out parameter for
      neuropsychological deficits. To determine whether serial magnetic resonance
      imaging (MRI) can provide information on brain atrophy in animals as well, mice
      that had undergone experimental SAH were scanned repeatedly after the bleeding.
      METHODS: Using a 7-T rodent MRI, six mice were evaluated for total hemispheric,
      cerebrospinal fluid (CSF) and hippocampal volumes on days 1, 2, 4, 21, 28, 42 and
      60 after experimental SAH or sham operation, respectively. RESULTS: Repeated MRI
      scanning demonstrated a very high reproducibility with minimum standard
      deviation. Nevertheless, no significant differences were found between the two
      groups concerning hemispherical volumes or hippocampal volumes. A transient but
      significant increase in CSF volume was detected on days 2 and 60 after SAH.
      Compared with the existing method, no MRI data on brain atrophy in mice after
      experimental SAH have been published. CONCLUSION: Repeated brain MRI in mice
      after experimental SAH did not provide additional information on brain atrophy.
      Our data suggest that this is not due to a lack of sensitivity of the method.
      Despite all promising details about MRI, our results should initiate careful
      consideration (additional sequences/other questions) before its further use in
      this certain area, especially since it is expensive and associated with demanding
      logistics.

PMID- 25398555
TI  - Differential profiling analysis of miRNAs reveals a regulatory role in low N
      stress response of Populus.
AB  - Nitrogen (N) is an essential mineral element for plant growth processes, and its
      availability severely affects the productivity of plants, especially trees.
      MicroRNAs (miRNAs) are a class of non-coding RNAs approximately 21 nucleotides in
      length that play important roles in plant growth, development and stress
      responses. To identify Populus miRNAs and their functions in response to
      nutrition stress, high-throughput sequencing was performed using Populus
      tomentosa plantlets treated with or without low concentrations of N. We
      identified 160 conserved miRNAs, 15 known but non-conserved miRNAs, 2 candidate
      novel miRNAs and 71 corresponding miRNA*s. Differential expression analysis
      showed that expression of the 21 conserved miRNA families was significantly
      altered. Real-time quantitative PCR (qPCR) was used to further validate and
      analyze the dynamic expression of the identified miRNAs. A total of 218 target
      genes from the low-N-responsive miRNAs were predicted, and their functions were
      further annotated in combination with Gene Ontology (GO) and Kyoto Encyclopedia
      of Genes and Genomes (KEGG) analyses. These results suggest that miRNAs play
      important roles in the response of Populus to low N stress. Furthermore, this
      study provides the first identification and profiles of N stress-responsive
      miRNAs from trees. 

PMID- 25398556
TI  - Functional features of crossmodal mismatch responses.
AB  - Research on brain mechanisms of deviance detection and sensory memory trace
      formation, best indexed by the mismatch negativity, mainly relied on the
      investigation of responses elicited by auditory stimuli. However, comparable less
      research reported the mismatch negativity elicited by somatosensory stimuli. More
      importantly, little is known on the functional features of mismatch deviant and
      standard responses across different sensory modalities. To directly compare
      different sensory modalities, we adopted a crossmodal roving paradigm and
      collected event-related potentials elicited by auditory, non-nociceptive
      somatosensory, and nociceptive trains of stimuli, during Active and Passive
      attentional conditions. We applied a topographical segmentation analysis to
      cluster successive scalp topographies with quasi-stable landscape of significant
      differences to extract crossmodal mismatch responses. We obtained three main
      findings. First, across different sensory modalities and attentional conditions,
      the formation of a standard sensory trace became robust mainly after the second
      stimulus repetition. Second, the neural representation of a modality deviant
      stimulus was influenced by the preceding sensory modality. Third, the mismatch
      negativity significantly covaried between Active and Passive attentional
      conditions within the same sensory modality, but not between different sensory
      modalities. These findings provide robust evidence that, while different
      modalities share a similar process of standard trace formation, the process of
      deviance detection is largely modality dependent. 

PMID- 25398557
TI  - Proprioceptively guided reaching movements in 3D space: effects of age, task
      complexity and handedness.
AB  - Aging is associated with impaired upper limb proprioceptive acuity, as reflected
      by decreased position matching accuracy with increasing task complexity and
      movement extent. Most studies have primarily used single-joint or planar
      paradigms to examine age-related changes in proprioception. It is unclear whether
      these changes can be generalized to more complex multi-joint movements, where
      additional sensory feedback may affect performance. Since age-related declines in
      cognitive function may impair the ability to integrate multiple sources of
      sensory feedback, deficits in position matching ability in older adults may
      persist when tasks are performed in three-dimensional space. The accuracy with
      which young and older participants reproduced remembered reference hand positions
      was assessed under different experimental conditions. Participants matched target
      locations located directly to the front or 45 degrees  to the side relative to
      the midline using the preferred and non-preferred arms. Either the same (i.e.,
      ipsilateral matching) or the opposite (i.e., contralateral matching) arm was used
      to reproduce the target location. No differences in matching accuracy were found
      between young and older participants when matching ipsilaterally. When matching
      contralaterally, accuracy was worse in older participants for target locations
      located to the side, which may reflect age-related changes in the perception of
      peripersonal space. In contrast to previous studies, accuracy did not differ
      between the preferred and non-preferred arms in either group. These results
      extend previous findings demonstrating age-related impairments in
      proprioceptively guided arm movements when interhemispheric transfer is required.

PMID- 25398558
TI  - The developmental trajectory of pointing perception in the first year of life.
AB  - The present study investigated the development of the neural basis of pointing
      perception in 6-month- and 13-month-old infants. In a spatial-cueing paradigm,
      infants were presented with a peripheral target followed by a hand pointing
      toward (congruent condition) or away (incongruent condition) from the previously
      cued location. EEG responses to the presentation of the hand were measured.
      Thirteen-month-olds demonstrated larger amplitudes of ERP component P400 to
      incongruent compared to congruent pointing gestures over posterior temporal
      areas; 6-month-olds did not show any differential activation. This result
      suggests that the neural correlates of pointing perception undergo substantial
      development between 6 and 13 months of age. 

PMID- 25398559
TI  - Erratum to: Differing coagulation profiles of patients with monoclonal gammopathy
      of undetermined significance and multiple myeloma.

PMID- 25398560
TI  - Inhibition-induced forgetting: when more control leads to less memory.
AB  - The ability to inhibit prepotent responses is a core executive function, but the
      relation of response inhibition to other cognitive operations is poorly
      understood. In the study reported here, we examined inhibitory control through
      the lens of incidental memory. Participants categorized face stimuli by gender in
      a go/no-go task (Experiments 1 and 2) or a stop-signal task (Experiment 3) and,
      after a short delay, performed a surprise recognition memory task for those
      faces. Memory was impaired for stimuli presented during no-go and stop trials
      compared with those presented during go trials. Experiment 4 showed that this
      inhibition-induced forgetting was not attributable to event congruency. In
      Experiment 5, we combined a go/no-go task with a dot-probe test and found that
      probe detection during no-go trials was inferior to that on go trials. This
      result supports the hypothesis that inhibition-induced forgetting occurs when
      response inhibition shunts attentional resources from perceptual stimulus
      encoding to action control. 

PMID- 25398561
TI  - Secondhand smoke exposure and serum cotinine levels among current smokers in the
      USA.
AB  - BACKGROUND: Secondhand smoke (SHS) likely provides additional exposure to
      nicotine and toxins for smokers, but has been understudied. Our objective was to
      determine whether SHS exposure among smokers yields detectable differences in
      cotinine levels compared with unexposed smokers at the population level. METHODS:
      Using the US National Health and Nutrition Examination Survey (NHANES) for the
      years 1999-2012, we compared serum cotinine levels of 4547 current adult
      cigarette smokers stratified by self-reported SHS exposure sources (home and/or
      work) and smoking intensity. A weighted multivariable linear regression model
      determined the association between SHS exposure and cotinine levels among
      smokers. RESULTS: Smokers with SHS exposure at home (43.8%) had higher cotinine
      levels (beta=0.483, p<=0.001) compared with those with no SHS exposure at home
      after controlling for the number of cigarettes smoked per day and number of days
      smoked in the previous 5 days, survey year, age, gender and education. Smokers
      with SHS exposure at work (20.0%) did not have significantly higher cotinine
      levels after adjustment. The adjusted geometric mean cotinine levels of light
      smokers (1-9 cigarettes per day) with no SHS exposure, exposure at work only,
      home only, and both home and work were 52.0, 62.7, 67.2, 74.4 ng/mL,
      respectively, compared with 219.4, 220.9, 255.2, 250.5 ng/mL among moderate/heavy
      smokers (>=10 cigarettes per day). CONCLUSIONS: Smokers living in residences
      where others smoke inside the home had significantly higher cotinine levels than
      smokers reporting no SHS exposure, regardless of individual smoking intensity.
      Future research should target the role that SHS exposure may have in nicotine
      dependence, cessation outcomes and other health impacts among smokers.

PMID- 25398562
TI  - Abrupt nicotine reduction as an endgame policy: a randomised trial.
AB  - OBJECTIVE: To determine if smokers unmotivated to quit reduce usual cigarette
      consumption when cigarettes priced according to nicotine content are made
      available. METHODS: Randomised, parallel-group, trial (ACTRN12612000914864)
      undertaken in Wakatipu/Central Otago, New Zealand. Dependent adult daily smokers
      unmotivated to quit were randomly allocated to an intervention group provided
      with 12 weeks supply of free very low nicotine content (VLNC) cigarettes, or to a
      control group, who were free to purchase their usual cigarette brand over the
      same period. The primary outcome was change from baseline in the daily mean
      number of usual cigarettes smoked over the previous week, measured at 12 weeks.
      Secondary outcomes at 6 and 12 weeks included cigarettes smoked per week (also
      measured at weeks 1-6 and 9), salivary cotinine, tobacco dependence, smoking
      satisfaction/craving, behavioural addiction to smoking, autonomy over smoking,
      motivation to stop, price at which participants would purchase VLNC cigarettes,
      quitting and adverse events. RESULTS: Thirty-three smokers were randomised (17
      intervention, 16 control). A NZ$15 price differential (per pack of 20) based on
      nicotine content led to a halving in the mean number of cigarettes smoked per day
      over the previous week, a reduction in tobacco dependence and an increase in
      quitting. Intervention participants smoked a similar total number of cigarettes
      (usual plus VLNC) as those in the control group, exposing them to a similar level
      of toxicants. CONCLUSIONS: Smokers unmotivated to quit reduce their usual
      cigarette consumption (and thus nicotine exposure) when VLNC cigarettes are made
      available at a significantly reduced price.

PMID- 25398565
TI  - The Supreme Court judgment in Nicklinson: one step forward on assisted dying; two
      steps back on human rights: a commentary on the Supreme Court judgment in R
      (Nicklinson) v Ministry of Justice; R (AM) v Director of Public Prosecutions
      [2014] UKSC 38.

PMID- 25398563
TI  - Tethering of SUUR and HP1 proteins results in delayed replication of euchromatic
      regions in Drosophila melanogaster polytene chromosomes.
AB  - We analyze how artificial targeting of Suppressor of Under-Replication (SUUR) and
      HP1 proteins affects DNA replication in the "open," euchromatic regions. Normally
      these regions replicate early in the S phase and display no binding of either
      SUUR or HP1. These proteins were expressed as fusions with DNA-binding domain of
      GAL4 and recruited to multimerized UAS integrated in three euchromatic sites of
      the polytene X chromosome: 3B, 8D, and 18B. Using PCNA staining as a marker of
      ongoing replication, we showed that targeting of SUUR(GAL4DBD) and HP1(GAL4DBD)
      results in delayed replication of appropriate euchromatic regions. Specifically,
      replication at these regions starts early, much like in the absence of the fusion
      proteins; however, replication completion is significantly delayed. Notably,
      delayed replication was insufficient to induce underreplication. Recruitment of
      SUUR(GAL4DBD) and HP1(GAL4DBD) had distinct effects on expression of a mini-white
      reporter, found near UAS. Whereas SUUR(GAL4DBD) had no measurable influence on
      mini-white expression, HP1(GAL4DBD) targeting silenced mini-white, even in the
      absence of functional SU(VAR)3-9. Furthermore, recruitment of SUUR(GAL4DBD) and
      HP1(GAL4DBD) had distinct effects on the protein composition of target regions.
      HP1(GAL4DBD) but not SUUR(GAL4DBD) could displace an open chromatin marker,
      CHRIZ, from the tethering sites. 

PMID- 25398564
TI  - Improving outcomes in breast cancer for low and middle income countries.
AB  - Breast cancer is the most common cancer in women world-wide. Incidence rates in
      low- and middle-income countries (LMICs) are lower than in high income countries;
      however, the rates are increasing very rapidly in LMICs due to social changes
      that increase the risk of breast cancer. Breast cancer mortality rates in LMICs
      remain high due to late presentation and inadequate access to optimal care.
      Breast Surgery International brought together a group of breast surgeons from
      different parts of the world to address strategies for improving outcomes in
      breast cancer for LMICs at a symposium during International Surgical Week in
      Helsinki, Finland in August 2013. A key strategy for early detection is public
      health education and breast awareness. Sociocultural barriers to early detection
      and treatment need to be addressed. Optimal management of breast cancer requires
      a multidisciplinary team. Surgical treatment is often the only modality of
      treatment available in low-resource settings where modified radical mastectomy is
      the most common operation performed. Chemotherapy and radiotherapy require more
      resources. Endocrine therapy is available but requires accurate assessment of
      estrogen receptors status. Targeted therapy with trastuzumab is generally
      unavailable due to cost. The Breast Health Global Initiative guidelines for the
      early detection and appropriate treatment of breast cancer in LMICs have been
      specifically designed to improve breast cancer outcomes in these regions. Closing
      the cancer divide between rich and poor countries is a moral imperative and there
      is an urgent need to prevent breast cancer deaths with early detection and
      optimal access to treatment. 

PMID- 25398566
TI  - Doctor who acted as witness outside his competence was punished too severely,
      court rules.

PMID- 25398567
TI  - [Degenerative spinal diseases].

PMID- 25398568
TI  - [Degenerative and age-related alterations of the spine].
AB  - Degenerative alterations of the spine occur in an individual-specific manner with
      increasing age. This is not only dependent on external factors, such as hard
      physical labor over many years but can also be genetically influenced as
      demonstrated in recent studies. The spinal cord is well-protected within the
      spinal canal but can be impaired by degenerative alterations of the
      intervertebral discs and functional spinal segments. Depositions or narrowing of
      nerve structures can cause lasting pain or focal neurological deficits, such as
      paralysis or sensitivity disorders. These complaints can slowly develop over
      years, e.g. by a gradually increasing bony narrowing of the spinal canal (spinal
      canal stenosis) or can occur suddenly, e.g. an acute herniated disc. However, low
      back pain is much more common and occurs in approximately 80 % of people sometime
      during their lifetime. It is necessary to recognize the normal age-related
      anatomical alterations in magnetic resonance imaging (MRI), particularly for
      intervertebral discs in order to interpret these correctly. Knowledge of the
      spectrum of the various age-related degenerative processes which can occur in
      intervertebral discs and vertebral bodies is necessary to be able to
      differentiate them from pathological alterations. This is important because
      therapy decisions are often made as a direct result of MRI. 

PMID- 25398569
TI  - [Red flags in the diagnostics of back pain].
AB  - BACKGROUND: Low back pain is one of the most commonly occurring symptomatic
      complaints with a lifetime prevalence of 70 %. OBJECTIVE: The question of
      meaningful radiological diagnostics arises in connection with the diagnostics and
      treatment of low back pain as the common lead symptom. MATERIAL AND METHODS:
      Special clinical warning signs, so-called red flags, which are indicative of a
      specific cause of low back pain and of the necessity for possible treatment, are
      presented with special reference to the national treatment guidelines on low back
      pain. RESULTS: The presence of clinical warning signs or red flags and in
      particular the combination of several red flags increases the probability of a
      specific cause of low back pain and should be examined using radiological
      imaging. An uncomplicated low back pain in an otherwise healthy patient does not
      normally necessitate imaging.

PMID- 25398570
TI  - [Diagnostics and therapy of spinal disc herniation].
AB  - Degenerative processes in a movement segment of the vertebral column, which can
      potentially give rise to herniation of elements of the nucleus pulposus, are
      complex and of variable clinical and radiological dimensions; however the mere
      assumption that degenerative changes precede disc herniation remains a matter of
      debate. By definition, spinal disc herniation (SDH) refers to components of the
      gelatinous nucleus pulposus protruding beyond the dorsal level of the vertebral
      body margin through tears in the annulus fibrosus. Clinical presentation may
      include pain, paresis and sensory disturbances. Magnetic resonance imaging (MRI)
      is considered the gold standard in the diagnosis of SDH. In the majority of
      patients a conservative approach with physical therapy exercises and adequate
      analgesic and antiphlogistic medical treatment results in a substantial
      improvement of symptoms. 

PMID- 25398571
TI  - [Spinal canal stenosis].
AB  - Spinal stenosis is a narrowing of the spinal canal by a combination of bone and
      soft tissues, which can lead to mechanical compression of spinal nerve roots or
      the dural sac. The lumbal spinal compression of these nerve roots can be
      symptomatic, resulting in weakness, reflex alterations, gait disturbances, bowel
      or bladder dysfunction, motor and sensory changes, radicular pain or atypical leg
      pain and neurogenic claudication. The anatomical presence of spinal canal
      stenosis is confirmed radiologically with computerized tomography, myelography or
      magnetic resonance imaging and play a decisive role in optimal patient-oriented
      therapy decision-making. 

PMID- 25398572
TI  - [Postoperative spine].
AB  - Approximately 15-30 % of surgical procedures involving the lumbar spine are
      associated with complications that require further diagnostic work-up. The choice
      of imaging modality for postoperative complications depends on the extent,
      pattern and temporal evolution of the postoperative neurological signs and
      symptoms as well as on the preoperative clinical status, the surgical procedure
      itself and the underlying pathology. The interpretation of imaging findings, in
      particular the distinction between postoperative complications and normally
      expected nonspecific postoperative imaging alterations can be challenging and
      requires the integration of clinical neurological information and the results of
      laboratory tests. The combination of different imaging techniques might help in
      cases of equivocal imaging results.

PMID- 25398573
TI  - [European curriculum for further education in radiology].
AB  - The European training curriculum for radiology of the European Society of
      Radiology (ESR) aims to harmonize training in radiology in Europe. Levels I and
      II constitute the centerpiece of the curriculum. The ESR recommends a 5-year
      training period in radiology with 3 years of level I and 2 years of level II
      training. The undergraduate (U) level curriculum is conceived as a basis for
      teaching radiology in medical schools and consists of a modality-oriented U1
      level and an organ-based U2 level. Level III curricula provide contents for
      subspecialty and fellowship training after board certification in radiology. The
      curricular contents of all parts of the European Training Curriculum are divided
      into the sections knowledge, skills as well as competences and attitudes. The
      European training curriculum is meant to be a recommendation and a basis for the
      development of national curricula, but is not meant to replace existing national
      regulations. 

PMID- 25398574
TI  - The nervous and the immune systems: conspicuous physiological analogies.
AB  - From all biological constituents of complex organisms, two are highly
      sophisticated: the nervous and the immune systems. Interestingly, their goals and
      processes appear to be distant from each other; however, their physiological
      mechanisms keep notorious similarities. Both construct intelligence, learn from
      experience, and keep memory. Their precise responses to innumerable stimuli are
      delicately modulated, and the exposure of the individual to thousands of
      potential challenges integrates their functionality; they use a large part of
      their constituents not in excitatory activities but in the maintenance of
      inhibitory mechanisms to keep silent vast intrinsic potentialities. The nervous
      and immune systems are integrated by a basic cell lineage (neurons and
      lymphocytes, respectively) but each embodies countless cell subgroups with
      different and specialized deeds which, in contrast with cells from other organs,
      labyrinthine molecular arrangements conduct to "one cell, one function". Also,
      nervous and immune actions confer identity that differentiates every individual
      from countless others in the same species. Both systems regulate and potentiate
      their responses aided by countless biological resources of variable intensity:
      hormones, peptides, cytokines, pro-inflammatory molecules, etc. How the immune
      and the nervous systems buildup memory, learning capability, and exquisite
      control of excitatory/inhibitory mechanisms constitute major intellectual
      challenges for contemporary research. 

PMID- 25398575
TI  - Choosiness, a neglected aspect of preference functions: a review of methods,
      challenges and statistical approaches.
AB  - Animals are faced with many choices and a very important one is the choice of a
      mating partner. Inter-individual differences in mating preferences have been
      studied for some time, but most studies focus on the location of the peak
      preference rather than on other aspects of preference functions. In this review,
      we discuss the role of variation in choosiness in inter-sexual selection. We
      define individual-level choosiness as the change in mating propensity in response
      to different stimulus signals. We illustrate general issues in estimating aspects
      of preference functions and discuss experimental setups for quantifying variation
      in choosiness with a focus on choices based on acoustic signals in insects. One
      important consideration is whether preferences are measured sequentially one
      stimulus at a time or in competitive multiple-choice setups; the suitability of
      these alternatives depends on the ecology of the study species. Furthermore, we
      discuss the usefulness of behavioural proxies for determining preference
      functions, which can be misleading if the proxies are not linearly related to
      mating propensity. Finally, we address statistical approaches, including the use
      of function-valued trait analysis, for studying choosiness. Most of the
      conclusions can be generalized beyond acoustic signals in insects and to choices
      in non-sexual contexts.

PMID- 25398576
TI  - Eye movements of vertebrates and their relation to eye form and function.
AB  - The types of eye movements shown by all vertebrates originated in the earliest
      fishes. These consisted of compensatory movements, both vestibular and visual, to
      prevent image motion, and saccades to relocate gaze. All vertebrates fixate food
      items with their heads to enable ingestion, but from teleosts onwards some
      species also use eye movements to target particular objects, especially food. Eye
      movement use is related to the resolution distribution in the retina, with eyes
      that contain foveas, or areas of high ganglion cell density, being more likely to
      make targeting eye movements, not seen in animals with more uniform retinas.
      Birds, in particular, tend mainly to use head movements when shifting gaze. Many
      birds also make translatory head saccades (head bobbing) when walking. It is
      common for animals to use both eyes when locating food items ahead, but the use
      of binocular disparity for distance judgment is rare, and has only been
      demonstrated in toads, owls, cats and primates. Smooth tracking with eyes alone
      is probably confined to primates. The extent of synchrony and directional
      symmetry in the movements of the two eyes varies greatly, from complete
      independence in the sandlance and chameleon, to perfect coordination in primates.

PMID- 25398577
TI  - Spider joint hair sensilla: adaptation to proprioreceptive stimulation.
AB  - Adding to previous efforts towards a better understanding of the remarkable
      diversity of spider mechanosensitive hair sensilla, this study examines hairs of
      Cupiennius salei most likely serving a proprioreceptive function. At the tibia
      metatarsus joint of all walking legs, there are two opposing groups of hairs
      ventrally on the tibia (20 hairs) and metatarsus (75 hairs), respectively. These
      hairs deflect each other when the joint flexes during locomotion, reversibly
      interlocking by microtrichs on their hair shafts. The torque resisting the hair
      deflection into the direction of natural stimulation is smaller by up to two
      powers of ten than that for the other directions. The torsional restoring
      constant S of the hair suspension is about 10(-10) Nm rad(-1) in the preferred
      direction, up to a hair deflection angle of 30 degrees  (mean of natural
      deflection angles). Joint movements were imposed in ranges and at rates measured
      in walking spiders and sensory action potentials recorded. Within the natural
      step frequencies (0.3-3 Hz) the rate of action potentials follows the velocity of
      hair deflection. All findings point to the morphological, mechanical, and
      physiological adaptedness of the joint hair sensilla to their proprioreceptive
      stimulation during locomotion. 

PMID- 25398578
TI  - Initial and long-term evaluation of patients with Alzheimer's after
      hospitalization in cognitive and behavioural units: the EVITAL study design.
AB  - BACKGROUND: Alzheimer's disease and related disorders are characterized by
      cognitive impairment associated with behavioral and psychological symptoms of
      dementia. These symptoms have significant consequences for both the patient and
      his family environment. While risk factors for behavioral disorders have been
      identified in several studies, few studies have focused on the evolution of these
      disorders. Moreover, it is important to identify factors linked to the long-term
      evolution of behavioral disorders, as well as patients' and caregivers' quality
      of life. Our purpose is to present the methodology of the EVITAL study, which
      primary objective is to determine the factors associated with the evolution of
      behavioral disorders among patients with Alzheimer's disease and related
      disorders during the year following their hospitalization in cognitive and
      behavioral units. Secondary objectives were 1) to assess the factors related to
      the evolution of behavioral disorders during hospitalization in cognitive and
      behavioral units; 2) to identify the factors linked to patients' and caregivers'
      quality of life, as well as caregivers' burden; 3) to assess the factors
      associated with rehospitalization of the patients for behavioral disorders in the
      year following their hospitalization in cognitive and behavioral units.
      METHOD/DESIGN: A multicenter, prospective cohort of patients with Alzheimer's
      disease and related disorders as well as behavioral disorders who are
      hospitalized in cognitive and behavioral units. The patients will be included in
      the study for a period of 24 months and followed-up for 12 months. Socio
      demographic and environmental data, behavioral disorders, medications, patients
      and caregivers quality of life as well as caregivers burden will be assessed
      throughout hospitalization in cognitive and behavioral units. Follow-up will be
      performed at months 3, 6 and 12 after hospitalization. Socio-demographic and
      environmental data, behavioral disorders, medications, patients and caregivers
      quality of life, unplanned rehospitalization as well as caregivers burden will
      also be assessed at each follow-up interview. DISCUSSION: The present study
      should help better identify the factors associated with reduction or
      stabilization of the behavioral and psychological symptoms of dementia in
      patients with Alzheimer's disease. It could therefore help clinicians to better
      manage these symptoms. TRIAL REGISTRATION: Clinical Trials NCT01901263.
      Registered July 9, 2013.

PMID- 25398579
TI  - Interstitial lung disease induced by alectinib (CH5424802/RO5424802).
AB  - A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV
      lung adenocarcinoma was administered the selective anaplastic lymphoma kinase
      inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the
      102nd day, chest computed tomography showed diffuse ground glass opacities.
      Laboratory data revealed high serum levels of KL-6, SP-D and lactate
      dehydrogenase without any clinical symptoms. There was no evidence of infection.
      Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and
      transbronchial lung biopsy showed mild thickening of alveolar septa and
      lymphocyte infiltration. Interstitial lung disease was judged to be related to
      alectinib based on improvements in imaging findings and serum biomarkers after
      discontinuation of alectinib. To our knowledge, this is the first reported case
      of alectinib-induced interstitial lung disease. Alectinib is a promising drug for
      ALK-rearranged non-small cell lung cancer. Clinical trials of this selective
      anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation
      of its long-term safety profile. 

PMID- 25398580
TI  - Adenocarcinoma arising at a colostomy site with inguinal lymph node metastasis:
      report of a case.
AB  - Inguinal lymph node metastasis from adenocarcinoma arising at a colostomy site is
      extremely rare, and the significance of surgical resection for metastatic
      inguinal lymph nodes has not been established. An 82-year-old woman who had
      undergone abdominoperineal resection 27 years earlier was admitted to our
      hospital complaining of bleeding from a colostomy. Physical examination revealed
      that a tumor at the colostomy site directly invaded into the peristomal skin, and
      that a left inguinal lymph node was firm and swollen. Positron emission
      tomography/computed tomography scan demonstrated accumulation of (18)F
      fluorodeoxy glucose into both the colostomy tumor and the left swollen inguinal
      lymph node, while there was no evidence of metastasis to liver or lungs. She
      underwent open left hemicolectomy with wide local resection of the colostomy, and
      dissection of left inguinal lymph nodes. Histological diagnosis was a moderately
      differentiated adenocarcinoma that directly invaded into the surrounding skin and
      metastasized to the left inguinal lymph node. The patient has been followed up
      for >5 years without any sign of recurrence. In general, inguinal lymph node
      metastasis from colorectal cancers is regarded as a systemic disease with a poor
      prognosis, and so systemic chemotherapy and radiotherapy, but not surgical lymph
      node dissection, are recommended. Considering the lymphatic drainage route in the
      present case, inguinal lymph node metastasis does not represent a systemic
      disease but rather a sentinel nodal metastasis from adenocarcinoma at a colostomy
      site. Surgical dissection of metastatic inguinal lymph nodes should be considered
      to enable a favorable prognosis in the absence of distant metastasis to other
      organs. 

PMID- 25398581
TI  - A double-blind randomized Phase II study of olanzapine 10 mg versus 5 mg for
      emesis induced by highly emetogenic chemotherapy.
AB  - A randomized Phase II dose-finding trial comparing olanzapine 10 mg with
      olanzapine 5 mg for patients receiving highly emetogenic chemotherapy with
      cisplatin was started in June 2014. The purpose of the trial is to evaluate the
      efficacy and safety of the two olanzapine doses and to determine which is more
      promising as a test arm for comparison with the current standard antiemetic care
      (a combination of aprepitant, a 5-HT3 receptor antagonist and dexamethasone) in a
      subsequent Phase III trial. Patients receiving cisplatin-containing regimens will
      be randomized to the olanzapine 10 or 5 mg arm. A total of 150 patients will be
      accumulated from nine institutions over 2 years. The primary endpoint is complete
      response defined as no emetic episodes and no use of rescue medications in the
      delayed (24-120 h) phase. This trial has been registered at the UMIN Clinical
      Trials Registry as UMIN000014214. 

PMID- 25398582
TI  - Successful treatment of metastatic rhabdomyosarcoma with radiochemotherapy and
      allogeneic hematopoietic stem cell transplantation.
AB  - We report a case of a 21-year-old man with alveolar rhabdomyosarcoma primarily in
      the right hand with lymph node, lung, bone and bone marrow metastases. Complete
      remission was achieved after intensive chemotherapy and radiotherapy of the
      primary and metastatic sites, followed by allogeneic peripheral blood stem cell
      transplantation with reduced-intensity conditioning from a single HLA-DR locus
      mismatched mother. The patient remained relapse-free for 41 months after the
      diagnosis. Considering that the conventional treatment for rhabdomyosarcoma with
      multiple risk factors (old age, bone or bone marrow involvement, unfavorable
      primary sites and >= 3 metastases) is associated with a poor prognosis (5%
      probability of a 3-year event-free survival), the graft-versus-tumor effect may
      have contributed to his sustained relapse-free survival. Allogeneic hematopoietic
      stem cell transplantation for rhabdomyosarcoma should be done by experienced
      clinical oncologists on properly designed controlled trials.

PMID- 25398583
TI  - Implementation of cervical cancer screening and prevention in China--challenges
      and reality.
AB  - This article summarizes great efforts that Chinese scholars had made in fighting
      against cervical cancer from aspects of the epidemiology, etiology, population
      based screening studies, novel screening technology development, guideline,
      strategy and policy making and population delivery. After decades of continuous
      efforts, Chinese scientists successfully translated their scientific discovery to
      appropriate screening product development and eventually, delivered it to the
      whole population. We hope our experience could serve as a 'case-story' for cancer
      prevention in other low- and middle-income countries. Moreover, challenges
      confronted in the prevention and control of cervical cancer in China are reviewed
      as well to appeal for future multi-collaborations and potential solutions to
      acquire the final success of the campaign. 

PMID- 25398585
TI  - Temporal Artery Thermometry to Detect Pediatric Fever.
AB  - This research investigated effectiveness of temporal artery thermometry (TAT) to
      detect high rectal fever in children >= 91 days and <= 4 years old. Rectal
      temperature was initially evaluated immediately followed by TAT. As expected, the
      difference between mean rectal (38.05 +/- .99  degrees C) and mean TA (37.55 +/-
      .8  degrees C) temperatures in subjects (N = 239) was significant (p < .0001).
      Linear regression revealed TAT underestimated rectal thermometry with greater
      frequency at higher temperatures. This observation provides probable explanation
      for the disparity between these thermometry methods. A TAT sensitivity of 75% and
      specificity of 85% were determined for detecting high fever (39  degrees C)-a
      finding clinically unacceptable. In contrast, among the small number of injured
      subjects enrolled, TAT detected high rectal fever with 100% sensitivity and
      specificity. This finding, if confirmed, suggests TAT screening for well and
      injured children has potential for clinical practice by diminishing rectal
      measurements and their associated risks in the acute care and/or ambulatory
      practice setting.

PMID- 25398584
TI  - Multicentre study of investigation and management of inpatient hyponatraemia in
      the UK.
AB  - PURPOSE: Hyponatraemia is associated with significant morbidity and mortality.
      The objectives of this study were to evaluate the investigation and management of
      hyponatraemia and to assess the use of different therapeutic modalities and their
      effectiveness in routine practice. STUDY DESIGN: This multicentre, retrospective,
      observational study was conducted at three acute NHS Trusts in March 2013. A
      retrospective chart review was performed on the first 100 inpatients with serum
      sodium (sNa) <=128 mmol/L during hospitalisation. RESULTS: One hundred patients
      (47 male, 53 female) with a mean+/-SD age of 71.3+/-15.4 years and nadir sNa of
      123.4+/-4.3 mmol/L were included. Only 23/100 (23%) had measurements of paired
      serum and urine osmolality and sodium, while 31% had an assessment of adrenal
      reserve. The aetiology of hyponatraemia was unrecorded in 58% of cases. The mean
      length of hospital stay was 17.5 days with an inpatient mortality rate of 16%. At
      hospital discharge, 53/84 (63.1%) patients had persistent hyponatraemia,
      including 20/84 (23.8%) with sNa <130 mmol/L. Overall 37/100 (37%) patients did
      not have any treatment for hyponatraemia. Among 76 therapeutic episodes, the most
      commonly used treatment modalities were isotonic saline in 38/76 cases (50%) and
      fluid restriction in 16/76 (21.1%). Fluid restriction failed to increase sNa by
      >1 mmol/L/day in 8/10 (80%) cases compared with 4/26 (15.4%) for isotonic saline.
      CONCLUSIONS: Underinvestigation and undertreatment of hyponatraemia is a common
      occurrence in UK clinical practice. Therefore, development of UK guidelines and
      introduction of electronic alerts for hyponatraemia should be considered to
      improve clinical practice.

PMID- 25398586
TI  - Development of a hexahistidine-3* FLAG-tandem affinity purification method for
      endogenous protein complexes in Pichia pastoris.
AB  - We developed a method for efficient chromosome tagging in Pichia pastoris, using
      a useful tandem affinity purification (TAP) tag. The TAP tag, designated and used
      here as the THF tag, contains a thrombin protease cleavage site for removal of
      the TAP tag and a hexahistidine sequence (6* His) followed by three copies of the
      FLAG sequence (3* FLAG) for affinity purification. Using this method, THF-tagged
      RNA polymerases I, II, and III were successfully purified from P. pastoris. The
      method also enabled us to purify the tagged RNA polymerase II on a large scale,
      for its crystallization and preliminary X-ray crystallographic analysis. The
      method described here will be widely useful for the rapid and large-scale
      preparation of crystallization grade eukaryotic multi-subunit protein complexes. 

PMID- 25398588
TI  - Can Fear, Pain, and Muscle Tension Discriminate Vaginismus from
      Dyspareunia/Provoked Vestibulodynia? Implications for the New DSM-5 Diagnosis of
      Genito-Pelvic Pain/Penetration Disorder.
AB  - Fear has been suggested as the crucial diagnostic variable that may distinguish
      vaginismus from dyspareunia. Unfortunately, this has not been systematically
      investigated. The primary purpose of this study, therefore, was to investigate
      whether fear as evaluated by subjective, behavioral, and psychophysiological
      measures could differentiate women with vaginismus from those with
      dyspareunia/provoked vestibulodynia (PVD) and controls. A second aim was to re
      examine whether genital pain and pelvic floor muscle tension differed between
      vaginismus and dyspareunia/PVD sufferers. Fifty women with vaginismus, 50 women
      with dyspareunia/PVD, and 43 controls participated in an experimental session
      comprising a structured interview, pain sensitivity testing, a filmed
      gynecological examination, and several self-report measures. Results demonstrated
      that fear and vaginal muscle tension were significantly greater in the vaginismus
      group as compared to the dyspareunia/PVD and no-pain control groups. Moreover,
      behavioral measures of fear and vaginal muscle tension were found to discriminate
      the vaginismus group from the dyspareunia/PVD and no-pain control groups. Genital
      pain did not differ significantly between the vaginismus and dyspareunia/PVD
      groups; however, genital pain was found to discriminate both clinical groups from
      controls. Despite significant statistical differences on fear and vaginal muscle
      tension variables between women suffering from vaginismus and dyspareunia/PVD, a
      large overlap was observed between these conditions. These findings may explain
      the great difficulty health professionals experience in attempting to reliably
      differentiate vaginismus from dyspareunia/PVD. The implications of these data for
      the new DSM-5 diagnosis of Genito-Pelvic Pain/Penetration Disorder are discussed.

PMID- 25398587
TI  - Three new cases of late-onset cblC defect and review of the literature
      illustrating when to consider inborn errors of metabolism beyond infancy.
AB  - BACKGROUND: The cblC defect is a rare inborn error of intracellular cobalamin
      metabolism. Biochemical hallmarks are elevated homocysteine and low methionine in
      plasma accompanied by methylmalonic aciduria. Due to the heterogeneous clinical
      picture, patients with the late-onset form of the disease (onset >12 months) come
      to the attention of diverse medical specialists, e.g. paediatricians,
      neurologists, nephrologists, psychiatrists or haematologists. The report reviews
      the published clinical data and adds three new cases to raise awareness for this
      severe but often treatable disease. METHODS: The Pubmed and the Cochrane
      databases were searched for clinical reports on cblC patients and three
      unreported cases are presented to illustrate the clinical spectrum. RESULTS:
      Reports on 58 cases (30 females, 22 males, 6 = no information) and the three new
      cases underlined the clinical heterogeneity of the disease. Time between first
      symptoms and diagnosis ranged from three months to more than 20 years. Haemolytic
      uraemic syndrome and pulmonary hypertension were main presenting symptoms in
      preschool children. In older children/adolescents, psychiatric symptoms,
      cognitive impairment, ataxia and myelopathy were frequently observed while
      thromboembolic events and glomerulopathies were almost exclusively seen in
      adults. Brain atrophy, white matter lesions and myelopathy were frequently
      encountered. The majority of patients showed marked biochemical and clinical
      response to treatment with parenteral hydroxocobalamin combined with oral
      betaine, folate, carnitine and rarely methionine. The course was less favourable
      in late treated or untreated patients. CONCLUSIONS: The late-onset cblC defect is
      a rare disease and unfortunately, diagnosis is often delayed. Raising awareness
      for this disorder can significantly improve patients' outcome and perspective by
      timely initiation of targeted treatment. Newborn screening (NBS) for the cblC
      defect might be of benefit especially for late-onset patients since treatment
      seems efficient when initiated before irreversible organ damage. In general,
      inborn errors of metabolisms should be considered in unexplained medical cases at
      any age, especially in patients with multisystemic disease. More specifically,
      total homocysteine in plasma and methylmalonic acid in urine/plasma should be
      measured in unexplained neurologic, psychiatric, renal, haematologic and
      thromboembolic disease.

PMID- 25398589
TI  - The analysis on risk factors and clinical treatment of craniocerebral injury
      concurrent with acute kidney injury.
AB  - The main objective of this study was to investigate the risk factors and clinical
      treatment of craniocerebral injury concurrent with acute kidney injury. A total
      of 220 patients who suffered from craniocerebral injury from March 2010 to March
      2012 in our Hospital were prospectively analyzed. Craniocerebral injury was
      defined according to the medical history, the verification of CT, and some
      investigated scores. The acute kidney injury was defined as a relative 47%
      increase of serum creatinine. The method of multivariate logistic regression
      analysis was used to evaluate the possible risk factors associated with post
      craniocerebral injury concurrent with acute kidney injury. The clinical
      treatments of craniocerebral injury concurrent with acute kidney injury were also
      identified via experimental results, and the pathological mechanism of
      craniocerebral injury concurrent with acute kidney injury was found to be related
      to cerebral tissue lesions, but some potential factors were ambiguous. The
      incidence of acute kidney injury was 70.2% with craniocerebral injury. In
      hospital, mortality of acute kidney injury patients was 31.2%, which was 6.019
      times of non-acute kidney injury patients (p < 0.01). The incidence of acute
      kidney injury in patients with craniocerebral injury was 58.3%, which was
      significantly higher compared to moderate and mild groups (p < 0.01).
      Unconditional multivariate logistic regression analysis results revealed that
      lower score, elderly, and male were the independent predictors of acute kidney
      injury episodes. Finally, some important factors were worthy of detailed study
      and further investigation.

PMID- 25398590
TI  - Fibrin-sealant-delivered cisplatin chemotherapy versus cisplatin hyperthermic
      intraperitoneal perfusion chemotherapy for locally advanced gastric cancer
      without peritoneal metastases: a randomized phase-II clinical trial with a 40
      month follow-up.
AB  - A new intraoperative cisplatin administration method for patients with locally
      advanced gastric cancer (AGC) and without peritoneal metastasis, fibrin-sealant
      delivered cisplatin chemotherapy, was reported, and its safety, pharmacokinetics,
      and efficacy were compared with cisplatin hyperthermic intraperitoneal perfusion
      chemotherapy. Forty-two AGC patients were randomly divided into 2 groups: fibrin
      sealant-delivered cisplatin chemotherapy (FS) (n = 21) and cisplatin hyperthermic
      intraperitoneal perfusion chemotherapy (CHIC) (n = 21). Both groups received 120
      mg cisplatin after complete cytoreductive surgery. At different time points,
      cisplatin concentrations in patients' sera and urine samples were measured to
      determine time-dependent maximal concentration (Cmax) and the area under the
      curve (AUC). The primary and secondary end-points were overall survival (OS) and
      safety profiling, respectively. Occurrence of grade-3 to grade-4 liver or kidney
      dysfunction was less frequent in the FS group than in the CHIC group (28.6 % vs
      47.6 %). Cisplatin Cmax and AUC for the serum and urine of the FS patients were
      significantly lower than that of the CHIC patients. Elimination half-life of
      cisplatin in the FS group was significantly longer than in the CHIC group (24.1 h
      vs 14.2 h). After a median follow-up of 40 months, 1-, 2-, and 3-years OS were
      90.5 %, 71.4 %, and 61.9 % in the FS group, and 61.9 %, 47.6 %, and 42.8 % in the
      CHIC group, respectively. The median OS was 35.9 months in the FS group and 29.1
      months in the CHIC group. Fibrin-sealant-delivered cisplatin chemotherapy was as
      effective and had a favorable pharmacokinetic profile with similar survival
      outcomes as cisplatin hyperthermic intraperitoneal perfusion chemotherapy
      following complete cytoreductive surgery of locally advanced GC without
      peritoneal metastases.

PMID- 25398591
TI  - Effects of Traditional Chinese Medicine in Treatment of Breast Cancer Patients
      After Mastectomy: A Meta-Analysis.
AB  - The purpose of the present study is to investigate the clinical efficacy of
      traditional Chinese medicine (TCM) in treating breast cancer patients after
      mastectomy. We searched EMBASE, CENTRAL, MEDLINE, Chinese Biomedical Database,
      Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database
      (VIP), and PubMed to collect randomized controlled trials of TCM in treatment of
      breast cancer patients after mastectomy. Quality of the methodology was
      assessment in accordance with Cochrane 4.2.2 Handbook. All patients were divided
      into two groups: TCM group (TCM only or TCM plus conventional treatment) and
      control group (conventional treatment only). Effects of TCM on short-term
      clinical outcome, long-term survival rate, and incidence of adverse reaction were
      compared between the two groups. Twenty-nine studies were included in this meta
      analysis, involving a total of 3142 breast cancer patients. Meta-analyses showed
      that TCM could improve short-term treatment efficacy (Z = 7.67, RR = 1.59, 95% cl
      [1.41-1.80], P < 0.00001), extend 3-year (Z = 5.47, RR = 1.26, 95% cl [1.16
      1.37], P < 0.00001) and 5-year (Z = 5.53, RR = 1.17, 95% cl [1.11-1.24], P <
      0.00001) survival, reduce the incidence of adverse reactions in breast cancer
      patients after mastectomy. TCM provides beneficial and complementary effects in
      the treatment of breast cancer patients after mastectomy.

PMID- 25398592
TI  - Insulin-Like Growth Factor-1 Modulates Polycomb Cbx8 Expression and Inhibits
      Colon Cancer Cell Apoptosis.
AB  - Colon cancer is one of the leading causes of death in human beings. The
      pathogenesis of colon cancer is unclear. Recent reports indicate that Chromobox
      protein homolog 8 (Cbx8) and insulin-like growth factor-1 (IGF1) are associated
      with the pathogenesis of cancer. This study aims to investigate the role of Cbx8
      and IGF1 in facilitating colon cancer cell proliferation. In this study, human
      colon cancer cell line, HCT116 cells, was cultured using an in vitro study model.
      The expression of Cbx8 and IGF1R (IGF1 receptor) in HCT116 cells was observed
      with approaches of real-time RT-PCR, Western blotting, gene silencing, and gene
      overexpression. The results showed that HCT116 cells express both Cbx8 and IGF1R.
      Exposure of HCT116 cells to IGF1 increased the expression of Cbx8. Knockdown of
      Cbx8 induced HCT116 cell apoptosis. Overexpression of Cbx8 induced HCT116 cell
      proliferation. We conclude that IGF1 can promote the colon cancer cell line,
      HCT116 cell, proliferation via promoting Cbx8 expression. 

PMID- 25398593
TI  - Hyperperfusion Syndrome After Stenting for Intracranial Artery Stenosis.
AB  - Hyperperfusion syndrome (HPS) is a rare but potentially devastating postoperative
      complication developing after endarterectomy and carotid stenting. Limited
      information is available about this complication. The aim of this study was to
      assess the incidence of HPS and risk factors leading to its development. We
      retrospectively reviewed 178 consecutive cases of patients who underwent stenting
      of intracranial artery revascularization. We analyzed the association between HPS
      and patient's age, collateral vascular supply of the lesion, the interval between
      operation and the last occurrence of ischemic symptom, adequacy of blood pressure
      control after the operation, and other risk factors such as diabetes, smoking,
      hypertension, and gender. Of 178 included patients, we found HPS in six cases
      (3.4%). Failure to strictly control postoperative blood pressure, a less than 3
      week long interval between operation and the last occurrence of ischemic symptom,
      and poor collateral circulation were significantly associated with the
      development of HPS. The aforementioned factors are predictors for HPS. We argue
      that nitroprusside should not be used to control blood pressure after the
      operation because its use permits considerable blood pressure fluctuations.

PMID- 25398594
TI  - Molecular evolution of kobuviruses in cats.
AB  - Aichi virus, a causative agent of human gastroenteritis, is one of a number of
      animal viruses belonging to the genus Kobuvirus within the family Picornaviridae.
      The kobuvirus genome encodes several structural and nonstructural proteins; the
      capsid proteins encoded by the VP1 gene are key immunogenic factors. Here, we
      used the VP1 region to determine substitution rates and the time to the most
      recent common ancestor (TMRCA) by comparing feline kobuvirus (FKoVs) sequences
      with kobuvirus sequences isolated from members of other species. The substitution
      rate for FKoVs was 1.29 * 10(-2 )substitutions/site/year (s/s/y) and the TMRCA
      was 5.3 years. 

PMID- 25398595
TI  - The complete nucleotide sequence of chrysanthemum stem necrosis virus.
AB  - The complete genome sequence of chrysanthemum stem necrosis virus (CSNV) was
      determined using Roche 454 next-generation sequencing. CSNV is a tentative member
      of the genus Tospovirus within the family Bunyaviridae, whose members are
      arthropod-borne. This is the first report of the entire RNA genome sequence of a
      CSNV isolate. The large RNA of CSNV is 8955 nucleotides (nt) in size and contains
      a single open reading frame of 8625 nt in the antisense arrangement, coding for
      the putative RNA-dependent RNA polymerase (L protein) of 2874 aa with a predicted
      Mr of 331 kDa. Two untranslated regions of 397 and 33 nt are present at the 5'
      and 3' termini, respectively. The medium (M) and small (S) RNAs are 4830 and 2947
      nt in size, respectively, and show 99 % identity to the corresponding genomic
      segments of previously partially characterized CSNV genomes. Protein sequences
      for the precursor of the Gn/Gc proteins, N and NSs, are identical in length in
      all of the analysed CSNV isolates. 

PMID- 25398596
TI  - Actual versus ideal body weight for acute kidney injury diagnosis and
      classification in critically ill patients.
AB  - BACKGROUND: In the current acute kidney injury (AKI) definition, the urine output
      (UO) criterion does not specify which body weights (BW), i.e. actual (ABW) versus
      ideal (IBW), should be used to diagnose and stage AKI, leading to heterogeneity
      across research studies. METHODS: This is a single center, retrospective,
      observational study conducted at a tertiary referral hospital. All adult patients
      who were admitted to intensive care units (ICUs) at our institution for a minimum
      of 6 continuous hours between January and March 2010 and had a urinary catheter
      for hourly urine output monitoring were eligible for this study. Patients' AKI
      stages, based on UO criterion, were assessed by calculating each milliliter of
      urine per kilogram per hour, using ABW versus IBW. RESULTS: A total of 493 ICU
      patients were included in the analysis. The median ABW and IBW were 82 (IQR 68
      96) and 70 (IQR 60-77) kg, respectively. Using the IBW criterion, 154 patients
      (31.2%) were diagnosed with AKI, while 204 (41.4%) were diagnosed using the ABW
      measurement (P-value<.01). Patients who had AKI regardless of BW type had an
      adjusted odds ratio of 1.76 (95% CI 1.05-2.95) for 90-day mortality, whereas
      patients who had AKI according to ABW but not IBW had no significant increase in
      the risk of 90-day mortality, adjusted OR 0.76; (95% CI 0.25-1.91), compared to
      patients who had no AKI. CONCLUSIONS: Using ABW to diagnose and stage AKI by UO
      criterion is more sensitive and less specific than IBW. Based on the application
      of the definition, different BW types could be utilized.

PMID- 25398597
TI  - Differential modulation of S1PR(1-5) and specific activities of SphK and nSMase
      in pulmonary and cerebral tissues of rats exposed to hypobaric hypoxia.
AB  - Recent preclinical and clinical studies have unfolded the potential of
      pharmacological modulation of activities of sphingosine-1-phosphate (S1P)
      receptors and S1P metabolizing enzymes for the development of therapeutic
      interventions against a variety of pathologies. An understanding of differential
      and temporal effects of hypoxia exposure on the key components of S1P signalling
      would certainly aid in designing improved drug development strategies in this
      direction. In view of this, the aim of the present study was to assess the effect
      of progressive hypobaric hypoxia exposure on expression of S1P receptors (S1PR1
      5) and specific activities of S1P synthesizing enzymes--neutral sphingomyelinase
      (nSMase) and sphingosine kinase (Sphk) in pulmonary and cerebral tissues of rats
      exposed to simulated altitude of 21,000 feet in an animal decompression chamber.
      Along with this, development of cerebral and pulmonary edema and markers of
      inflammation were studied at 12, 24, and 48 h to validate our study model of
      hypobaric hypoxia-induced stress. The protein expression of S1PR1-5 and
      activities of Sphk and nSMase enzymes were observed to be dramatically affected
      by simulated hypobaric hypoxia exposure, concurrent with deterioration of
      pathology, with 12 h of exposure appearing to be the most critical of the various
      time points studied.

PMID- 25398598
TI  - Primary cilia exist in a small fraction of cells in trabecular bone and marrow.
AB  - Primary cilia are potent mechanical and chemical sensory organelles in cells of
      bone lineage in tissue culture. Cell culture experiments suggest that primary
      cilia sense fluid flow and this stimulus is translated through biochemical
      signaling into an osteogenic response in bone cells. Moreover, in vivo, primary
      cilia knockout in bone cells attenuates bone formation in response to loading.
      However, understanding the role of the primary cilium in bone mechanotransduction
      requires knowledge of its incidence and location in vivo. We used
      immunohistochemistry to quantify the number of cells with primary cilia within
      the trabecular bone tissue and the enclosed marrow of ovine cervical vertebrae.
      Primary cilia were identified in osteocytes, bone lining cells, and in cells
      within the marrow, but were present in only a small fraction of cells.
      Approximately 4% of osteocytes and 4.6% of bone lining cells expressed primary
      cilia. Within the marrow space, only approximately 1% of cells presented primary
      cilia. The low incidence of primary cilia may indicate that cilia either function
      as mechanosensors in a selected number of cells, function in concert with other
      mechanosensing mechanisms, or that the role of primary cilia in mechanosensing is
      secondary to its role in chemosensing or cellular attachment.

PMID- 25398599
TI  - The introduction of a lightweight mini vaporizer and malignant hyperthermia.

PMID- 25398600
TI  - The limitations of manually entered data in acute care environments.

PMID- 25398601
TI  - Evaluating a web-based paediatric infectious diseases journal club: more than
      just critical appraisal?

PMID- 25398602
TI  - Increasing adaptive behavior skill deficits from childhood to adolescence in
      autism spectrum disorder: role of executive function.
AB  - Almost half of all children with autism spectrum disorder have average cognitive
      abilities, yet outcome remains poor. Because outcome in HFASD is more related to
      adaptive behavior skills than cognitive level it is important to identify
      predictors of adaptive behavior. This study examines cognitive and demographic
      factors related to adaptive behavior, with specific attention to the role of
      executive function (EF) in youth with HFASD aged 4-23. There was a negative
      relationship between age and adaptive behavior and the discrepancy between IQ and
      adaptive behavior increased with age. EF problems contributed to lower adaptive
      behavior scores across domains. As such, it is important to target adaptive
      skills, and the EF problems that may contribute to them, in youth with HFASD. 

PMID- 25398603
TI  - Emergence of autism spectrum disorder in children from simplex families:
      relations to parental perceptions of etiology.
AB  - Current research describes a four-category scheme of Autism Spectrum Disorder
      (ASD) onset: early, regressive, plateau, delay + regression. To replicate
      prevalence of different onset types, ASD onset (per the Autism Diagnostic
      Interview--Revised) was examined in a large North American sample; for a subset,
      parents' causal beliefs were ascertained via the Revised Illness Perception
      Questionnaire to examine potential associations with ASD-onset types. Onset rates
      were similar across samples, with a slightly higher proportion of children in the
      subsample categorized with regression. Top-rated causes of ASD were genetics,
      brain structure, will of God, toxins in vaccines, and environmental pollution.
      Parents reporting regression more often believed that toxins in vaccines caused
      ASD. Influences on treatment selection and broader public-health ramifications
      are discussed.

PMID- 25398604
TI  - Knowledge and use of intervention practices by community-based early intervention
      service providers.
AB  - This study investigated staff attitudes, knowledge and use of evidence-based
      practices (EBP) and links to organisational culture in a community-based autism
      early intervention service. An EBP questionnaire was completed by 99 metropolitan
      and regionally-based professional and paraprofessional staff. Participants
      reported greater knowledge and use of EBPs compared to emerging and unsupported
      practices. Knowledge and use of EBPs were linked to each other independent of
      significant correlations with organisational culture and attitudes. Knowledge and
      use of EBPs was greater in metropolitan than regional locations and
      paraprofessionals reported greater use of unsupported practices and lower levels
      of knowledge and use of EBPs than professionals. The implications of these
      findings for the facilitation of knowledge transfer are discussed. 

PMID- 25398606
TI  - Health secretary tells NHS in England to sell land and use fewer agency staff and
      management consultants.

PMID- 25398605
TI  - Behavior and brain gene expression changes in mice exposed to preimplantation and
      prenatal stress.
AB  - Preimplantation culture of mouse embryos has been suggested to result in reduced
      anxiety-like behavior in adulthood. Here, we investigated the effects of in vitro
      fertilization (IVF), embryo culture, and different diets on anxiety-like behavior
      using the elevated plus maze (EPM). We hypothesized that exposure to suboptimal
      conditions during the preimplantation stage would interact with the suboptimal
      diet to alter behavior. The expression of genes related to anxiety was then
      assessed by quantitative real-time polymerase chain reaction in various brain
      regions. When fed a normal diet during gestation and a moderately high-fat
      Western diet (WD) postnatally, naturally conceived (NC) and IVF mice showed
      similar anxiety-like behavior on the EPM. However, when fed a low-protein diet
      prenatally and a high-fat diet postnatally (LP/HF), NC mice showed a modest
      increase in anxiety-like behavior, whereas IVF mice showed the opposite: a
      strongly reduced anxiety-like behavior on the EPM. The robust reduction in
      anxiety-like behavior in IVF males fed the LP/HF diets was, intriguingly,
      associated with reduced expression of MAO-A, CRFR2, and GABA markers in the
      hypothalamus and cortex. These findings are discussed in relation to the
      developmental origin of health and disease hypothesis and the 2-hit model, which
      suggests that 2 events, occurring at different times in development, can act
      synergistically with long-term consequences observed during adulthood. 

PMID- 25398607
TI  - Macrophage migration inhibitory factor is required for recruitment of scar
      associated macrophages during liver fibrosis.
AB  - Recruitment of peripheral monocytes to the liver is a key contributor to the
      response to injury. MIF can act as a chemokine and cytokine, regulating innate
      immune responses in many tissues and cell types. We hypothesized that MIF
      contributes to the progression of CCl4-induced hepatic fibrosis by regulating
      recruitment of SAM. SAMs dynamically regulate HSC activation and ECM degradation.
      To gain insight into the role of MIF in progression of liver fibrosis, we
      investigated markers of fibrosis and immune responses after chronic CCl4
      administration to female C57BL/6 and MIF(-/-) mice. Chronic CCl4 exposure
      increased activation of HSC in WT mice, indicated by increased expression of
      alphaSMA mRNA and protein, as well as mRNA for collagen 1alpha1; these responses
      were blunted in female MIF(-/-) mice. Despite lower activation of HSC in MIF(-/-)
      mice, accumulation of ECM was similar in WT and MIF(-/-)mice, suggesting a
      decreased rate of ECM degradation. Recruitment of SAMs was lower in MIF(-/-) mice
      compared with WT mice, both in their initial inflammatory phenotype, as well as
      in the later phase as proresolution macrophages. The decreased presence of
      resolution macrophages was associated with lower expression of MMP13 in MIF(-/-)
      mice. Taken together, these data indicate that MIF-dependent recruitment of SAMs
      contributes to degradation of ECM via MMP13, highlighting the importance of
      appropriate recruitment and phenotypic profile of macrophages in the resolution
      of fibrosis. 

PMID- 25398608
TI  - SNV-PPILP: refined SNV calling for tumor data using perfect phylogenies and ILP.
AB  - MOTIVATION: Recent studies sequenced tumor samples from the same progenitor at
      different development stages and showed that by taking into account the phylogeny
      of this development, single-nucleotide variant (SNV) calling can be improved.
      Accurate SNV calls can better reveal early-stage tumors, identify mechanisms of
      cancer progression or help in drug targeting. RESULTS: We present SNV-PPILP, a
      fast and easy to use tool for refining GATK's Unified Genotyper SNV calls, for
      multiple samples assumed to form a phylogeny. We tested SNV-PPILP on simulated
      data, with a varying number of samples, SNVs, read coverage and violations of the
      perfect phylogeny assumption. We always match or improve the accuracy of GATK,
      with a significant improvement on low read coverage. AVAILABILITY AND
      IMPLEMENTATION: SNV-PPILP, available at cs.helsinki.fi/gsa/snv-ppilp/, is written
      in Python and requires the free ILP solver lp_solve. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 25398609
TI  - UniRef clusters: a comprehensive and scalable alternative for improving sequence
      similarity searches.
AB  - MOTIVATION: UniRef databases provide full-scale clustering of UniProtKB sequences
      and are utilized for a broad range of applications, particularly similarity-based
      functional annotation. Non-redundancy and intra-cluster homogeneity in UniRef
      were recently improved by adding a sequence length overlap threshold. Our
      hypothesis is that these improvements would enhance the speed and sensitivity of
      similarity searches and improve the consistency of annotation within clusters.
      RESULTS: Intra-cluster molecular function consistency was examined by analysis of
      Gene Ontology terms. Results show that UniRef clusters bring together proteins of
      identical molecular function in more than 97% of the clusters, implying that
      clusters are useful for annotation and can also be used to detect annotation
      inconsistencies. To examine coverage in similarity results, BLASTP searches
      against UniRef50 followed by expansion of the hit lists with cluster members
      demonstrated advantages compared with searches against UniProtKB sequences; the
      searches are concise (~7 times shorter hit list before expansion), faster (~6
      times) and more sensitive in detection of remote similarities (>96% recall at e
      value <0.0001). Our results support the use of UniRef clusters as a comprehensive
      and scalable alternative to native sequence databases for similarity searches and
      reinforces its reliability for use in functional annotation.

PMID- 25398610
TI  - SplitMEM: a graphical algorithm for pan-genome analysis with suffix skips.
AB  - MOTIVATION: Genomics is expanding from a single reference per species paradigm
      into a more comprehensive pan-genome approach that analyzes multiple individuals
      together. A compressed de Bruijn graph is a sophisticated data structure for
      representing the genomes of entire populations. It robustly encodes shared
      segments, simple single-nucleotide polymorphisms and complex structural
      variations far beyond what can be represented in a collection of linear sequences
      alone. RESULTS: We explore deep topological relationships between suffix trees
      and compressed de Bruijn graphs and introduce an algorithm, splitMEM, that
      directly constructs the compressed de Bruijn graph in time and space linear to
      the total number of genomes for a given maximum genome size. We introduce suffix
      skips to traverse several suffix links simultaneously and use them to efficiently
      decompose maximal exact matches into graph nodes. We demonstrate the utility of
      splitMEM by analyzing the nine-strain pan-genome of Bacillus anthracis and up to
      62 strains of Escherichia coli, revealing their core-genome properties.

PMID- 25398611
TI  - M3D: a kernel-based test for spatially correlated changes in methylation
      profiles.
AB  - MOTIVATION: DNA methylation is an intensely studied epigenetic mark implicated in
      many biological processes of direct clinical relevance. Although sequencing-based
      technologies are increasingly allowing high-resolution measurements of DNA
      methylation, statistical modelling of such data is still challenging. In
      particular, statistical identification of differentially methylated regions
      across different conditions poses unresolved challenges in accounting for spatial
      correlations within the statistical testing procedure. RESULTS: We propose a non
      parametric, kernel-based method, M(3)D, to detect higher order changes in
      methylation profiles, such as shape, across pre-defined regions. The test
      statistic explicitly accounts for differences in coverage levels between samples,
      thus handling in a principled way a major confounder in the analysis of
      methylation data. Empirical tests on real and simulated datasets show an
      increased power compared to established methods, as well as considerable
      robustness with respect to coverage and replication levels.

PMID- 25398612
TI  - M-path: a compass for navigating potential metabolic pathways.
AB  - MOTIVATION: Construction of synthetic metabolic pathways promises sustainable
      production of diverse chemicals and materials. To design synthetic metabolic
      pathways of high value, computational methods are needed to expand present
      knowledge by mining comprehensive chemical and enzymatic information databases.
      Several computational methods have been already reported for the metabolic
      pathway design, but until now computation complexity has limited the diversity of
      chemical and enzymatic data used. RESULTS: We introduce a computational platform,
      M-path, to explore synthetic metabolic pathways including putative enzymatic
      reactions and compounds. M-path is an iterative random algorithm, which makes
      efficient use of chemical and enzymatic databases to find potential synthetic
      metabolic pathways. M-path can readily control the search space and perform well
      compared with exhaustively enumerating possible pathways. A web-based pathway
      viewer is also developed to check extensive metabolic pathways with evaluation
      scores on the basis of chemical similarities. We further produce extensive
      synthetic metabolic pathways for a comprehensive set of alpha amino acids. The
      scalable nature of M-path enables us to calculate potential metabolic pathways
      for any given chemicals.

PMID- 25398613
TI  - ViQuaS: an improved reconstruction pipeline for viral quasispecies spectra
      generated by next-generation sequencing.
AB  - MOTIVATION: The combined effect of a high replication rate and the low fidelity
      of the viral polymerase in most RNA viruses and some DNA viruses results in the
      formation of a viral quasispecies. Uncovering information about quasispecies
      populations significantly benefits the study of disease progression, antiviral
      drug design, vaccine design and viral pathogenesis. We present a new analysis
      pipeline called ViQuaS for viral quasispecies spectrum reconstruction using short
      next-generation sequencing reads. ViQuaS is based on a novel reference-assisted
      de novo assembly algorithm for constructing local haplotypes. A significantly
      extended version of an existing global strain reconstruction algorithm is also
      used. RESULTS: Benchmarking results showed that ViQuaS outperformed three other
      previously published methods named ShoRAH, QuRe and PredictHaplo, with
      improvements of at least 3.1-53.9% in recall, 0-12.1% in precision and 0-38.2% in
      F-score in terms of strain sequence assembly and improvements of at least 0.006
      0.143 in KL-divergence and 0.001-0.035 in root mean-squared error in terms of
      strain frequency estimation, over the next-best algorithm under various
      simulation settings. We also applied ViQuaS on a real read set derived from an in
      vitro human immunodeficiency virus (HIV)-1 population, two independent datasets
      of foot-and-mouth-disease virus derived from the same biological sample and a
      real HIV-1 dataset and demonstrated better results than other methods available.

PMID- 25398614
TI  - Local statistics allow quantification of cell-to-cell variability from high
      throughput microscope images.
AB  - MOTIVATION: Quantifying variability in protein expression is a major goal of
      systems biology and cell-to-cell variability in subcellular localization pattern
      has not been systematically quantified. RESULTS: We define a local measure to
      quantify cell-to-cell variability in high-throughput microscope images and show
      that it allows comparable measures of variability for proteins with diverse
      subcellular localizations. We systematically estimate cell-to-cell variability in
      the yeast GFP collection and identify examples of proteins that show cell-to-cell
      variability in their subcellular localization. CONCLUSIONS: Automated image
      analysis methods can be used to quantify cell-to-cell variability in microscope
      images.

PMID- 25398616
TI  - 25-hydroxyvitamin D serum level in children of different ethnicity living in
      Italy.
AB  - Several factors including ethnicity are known to influence 25(OH)D levels. The
      purpose of our study was to assess 25(OH)D levels among 1374 pediatric subjects
      of different ethnicity and to determine the prevalence of vitamin D deficiency
      and insufficiency among different ethnic groups. The prevalence of 25(OH)D <= 20
      ng/ml was 44.2, 65.2, 69.2, 54.0, and 44.8 % among Caucasians, Africans, North
      Africans, Indians, and others, respectively (P < 0.001). The median of 25(OH)D
      was 21.0 ng/ml (IQR = 14.0-29.6 ng/ml) for the cohort. Season of blood sampling,
      age, ethnicity, gestational age, birth weight, and z-score BMI were associated
      with 25(OH)D levels. Caucasians had higher median 25(OH)D levels than sub-Saharan
      Africans (P < 0.001), North Africans (P < 0.001), and Indians (P < 0.001). There
      were no significant differences in the median 25(OH)D levels between ethnic
      groups among infants, whereas for children older than 1 year we found significant
      differences in 25(OH)D levels in the different ethnic groups, compared to
      Caucasians. CONCLUSION: Ethnicity was correlated with 25(OH)D levels among
      children older than 1 year. We found a high prevalence of vitamin D deficiency
      and insufficiency after the first year of life, and this was more remarkable in
      non-Caucasian children.

PMID- 25398615
TI  - LDL and HDL transfer rates across peripheral microvascular endothelium agree with
      those predicted for passive ultrafiltration in humans.
AB  - The mechanisms by which LDLs and HDLs cross the vascular endothelium from plasma
      into interstitial fluid are not understood, and have never been studied in humans
      in vivo. We determined whether the plasma-to-lymph clearance rates of LDL and HDL
      conform with those predicted by passive ultrafiltration through intercellular
      pores, or if it is necessary to invoke an active process such as receptor
      mediated transcytosis. Plasma and afferent peripheral lymph were collected under
      steady-state conditions from 30 healthy men, and assayed for seven globular
      proteins of molecular radii 2.89-8.95 nm, complement C3, and apo AI, apo AII, and
      apo B. Plasma-to-lymph clearance rates of the seven proteins fitted the relation
      expected for molecules of their size when transported through two populations of
      pores of radius 4.95 and 20.1 nm. The same model parameters were then found to
      accurately predict the clearance rates of both HDL and LDL. The apparent
      clearance of complement C3, previously shown to be secreted by cultured
      endothelium, exceeded that predicted by the model. We conclude that the transport
      of HDL and LDL from plasma into interstitial fluid across the peripheral vascular
      endothelium in healthy humans can be explained by ultrafiltration without
      invoking an additional active process such as transcytosis. 

PMID- 25398617
TI  - Discovery and mapping of Brassica juncea Sdt 1 gene associated with determinate
      plant growth habit.
AB  - KEY MESSAGE: Newly discovered determinate plant growth habit in Brassica juncea
      is simply inherited and can help in architectural restructuring of Brassica
      oilseeds. Brassica juncea is naturally indeterminate. This growth habit tends to
      accentuate intra-plant competition for resources within the plant canopy, leading
      to unfilled seeds, immature pods and tip sterility. Recent identification of
      plants with determinate growth habit is expected to open up new avenues for plant
      architectural modifications in crop Brassicas. Plants with determinate plant
      growth habit were identified in progenies of resynthesized B. juncea as a de novo
      variation. F1 plants, developed from crosses of determinate mustard with natural
      indeterminate genotypes were indeterminate, indicating the dominance of
      indeterminacy. F2 and F3 segregation revealed monogenic recessive inheritance in
      the progenies studied. Gene for determinacy (Sdt 1 ) was mapped to the linkage
      group 15 of B. juncea. Sdt 1 was flanked by SSR markers SJ6842 and Ni4-A10 at
      distances of 15.9 cM and 14.0 cM, respectively. Determinate progenies showed
      significant variation for plant height, flowering time and productivity. There
      appeared to be no adverse association in terms of lower pod density, productivity
      or oil content. Determinacy was under control of single recessive gene, mapped to
      the linkage group 15 of B. juncea. Determinate progenies with high agronomic
      performance were identified.

PMID- 25398618
TI  - Expression of a cystatin transgene can confer resistance to root lesion nematodes
      in Lilium longiflorum cv. 'Nellie White'.
AB  - Lilium longiflorum cv. 'Nellie White' assumes a great economic importance as cut
      flowers, being one of the most valuable species (annual pot plants value above
      $20,000,000) in terms of wholesales in the US. The root lesion nematode
      Pratylenchus penetrans (RLN) constitutes one of the main pests for lily producers
      due to the significant root damage it causes. Our efforts have focused on the
      generation of soybean hairy roots (as a transient test model) and stable
      transgenic lilies overexpressing a modified rice cystatin (Oc-IDeltaD86)
      transgene and challenged with root lesion nematodes. Lily transformation was
      achieved by gene gun co-bombardment using both a pBluescript-based vector
      containing the cystatin gene and pDM307 that contains a bar gene for
      phosphinothricin selection. Both soybean hairy roots and lilies overexpressing
      the OcIDeltaD86 transgene exhibited enhanced resistance to RLN infection by means
      of nematode reduction up to 75 +/- 5% on the total number of nematodes. In
      addition, lily plants overexpressing OcIDeltaD86 displayed an increase of plant
      mass and better growth performance in comparison to wild-type plants, thereby
      demonstrating an alternative strategy for increasing the yield and reducing
      nematode damage to this important floral crop.

PMID- 25398619
TI  - Differences in price elasticities of demand for health insurance: a systematic
      review.
AB  - Many health insurance systems apply managed competition principles to control
      costs and quality of health care. Besides other factors, managed competition
      relies on a sufficient price-elastic demand. This paper presents a systematic
      review of empirical studies on price elasticity of demand for health insurance.
      The objective was to identify the differing international ranges of price
      elasticity and to find socio-economic as well as setting-oriented factors that
      influence price elasticity. Relevant literature for the topic was identified
      through a two-step identification process including a systematic search in
      appropriate databases and further searches within the references of the results.
      A total of 45 studies from countries such as the USA, Germany, the Netherlands,
      and Switzerland were found. Clear differences in price elasticity by countries
      were identified. While empirical studies showed a range between -0.2 and -1.0 for
      optional primary health insurance in the US, higher price elasticities between 
      0.6 and -4.2 for Germany and around -2 for Switzerland were calculated for
      mandatory primary health insurance. Dutch studies found price elasticities below 
      0.5. In consideration of all relevant studies, age and poorer health status were
      identified to decrease price elasticity. Other socio-economic factors had an
      unclear impact or too limited evidence. Premium level, range of premiums,
      homogeneity of benefits/coverage and degree of forced decision were found to have
      a major influence on price elasticity in their settings. Further influence was
      found from supplementary insurance and premium-dependent employer contribution. 

PMID- 25398620
TI  - Neighborhood deprivation and maternal psychological distress during pregnancy: a
      multilevel analysis.
AB  - Maternal psychosocial distress is conceptualized as an important factor
      underlying the association between neighborhood deprivation and pregnancy
      outcomes. However, empirical studies to examine effects of neighborhood
      deprivation on psychosocial distress during pregnancy are scant. Based on a large
      multicenter cohort of pregnant women in Montreal, we examined (1) the extent to
      which psychosocial distress is clustered at the neighborhood-level, (2) the
      extent to which the clustering is explained by neighborhood material or social
      deprivation, and (3) whether associations between neighborhood deprivation and
      psychosocial distress persist after accounting for neighborhood composition
      (individual-level characteristics) using multilevel analyses. For 5,218 women
      residing in 740 neighborhoods, a prenatal interview at 24-26 gestational weeks
      measured both general and pregnancy-related psychological distress using well
      validated scales: perceived stress, social support, depressive symptoms,
      optimism, commitment to the pregnancy, pregnancy-related anxiety, and maternal
      locus-of-control. Neighborhood deprivation indices were linked to study
      participants by their residential postal code. Neighborhood-level clustering
      (intraclass correlation) ranged from 1 to 2 % for perceived stress (lowest),
      optimism, pregnancy-related anxiety, and commitment to pregnancy to 4-6 % for
      perceived social support, depressive symptoms, and maternal locus of control
      (highest). Neighborhood material deprivation explained far more of the clustering
      (23-75 %) than did social deprivation (no more than 4 %). Although both material
      and social deprivation were associated with psychological distress in unadjusted
      analyses, the associations disappeared after accounting for individual-level
      socioeconomic characteristics. Our results highlight the importance of accounting
      for individual-level socioeconomic characteristics in studies of potential
      neighborhood effects on maternal mental health.

PMID- 25398621
TI  - A comparison of methods for converting DCE values onto the full health-dead QALY
      scale.
AB  - BACKGROUND: Preference elicitation techniques such as time trade-off (TTO) and
      standard gamble (SG) receive criticism for their complexity and difficulties of
      use. Ordinal techniques such as discrete choice experiment (DCE) are arguably
      easier to understand but generate values that are not anchored onto the full
      health-dead 1-0 quality-adjusted life-year (QALY) scale required for use in
      economic evaluation. METHODS: This article compares existing methods for
      converting modeled DCE latent values onto the full health-dead QALY scale: 1)
      anchoring DCE values using dead as valued in the DCE and 2) anchoring DCE values
      using TTO value for worst state to 2 new methods: 3) mapping DCE values onto TTO
      and 4) combining DCE and TTO data in a hybrid model. Models are compared using
      their ability to predict mean TTO health state values. DATA: We use postal DCE
      data (n = 263) and TTO data (n = 307) collected by interview in a general
      population valuation study of an asthma condition-specific measure (AQL-5D).
      RESULTS: New methods 3 and 4 using mapping and hybrid models are better able to
      predict mean TTO health state values (mean absolute difference [MAD], 0.052
      0.084) than the anchor-based methods (MAD, 0.075-0.093) and were better able to
      predict mean TTO health state values even when using in their estimation a
      subsample of the available TTO data. CONCLUSIONS: These new mapping and hybrid
      methods have a potentially useful role for producing values on the QALY scale
      from data elicited using ordinal techniques such as DCE for use in economic
      evaluation that makes best use of the desirable properties of each elicitation
      technique and elicited data. Further research is encouraged.

PMID- 25398622
TI  - Impact of Diabetes E-Consults on Outpatient Clinic Workflow.
AB  - BACKGROUND: An e-consult is an electronic communication system between
      clinicians, usually a primary care physician (PCP) and a medical or surgical
      specialist, regarding general or patient-specific, low complexity questions that
      would not need an in-person consultation. The objectives of this study were to
      understand and quantify the impact of the e-consult initiative on outpatient
      clinic workflow and outcomes. METHODS: We collected data from 5 different
      Veterans Affairs (VA) outpatient clinics and interviewed several physicians and
      staff members. We then developed a simulation model for a primary care team at an
      outpatient clinic. A detailed experimental study was conducted to determine the
      effects of factors, such as e-consult demand, view-alert notification arrivals,
      walk-in patient arrivals, and PCP unavailability, on e-consult cycle time.
      RESULTS: Statistical tests indicated that 4 factors related to outpatient clinic
      workflow were significant, and levels within each of the 4 significant factors
      resulted in statistically different e-consult cycle times. The arrival rate of
      electronic notifications, along with patient walk-ins, had a considerable effect
      on cycle time. Splitting the workload of an unavailable PCP among the other PCPs,
      instead of the current practice of allocating it to a single PCP, increases the
      system's ability to handle a much larger e-consult demand. CONCLUSIONS: The full
      potential of e-consults can only be realized if the workflow at the outpatient
      clinics is designed or modified to support this initiative. This study furthers
      our understanding of how e-consult systems can be analyzed and alternative
      workflows tested using statistical and simulation modeling to improve care
      delivery and outcomes.

PMID- 25398623
TI  - Exploring the response shift effect on the quality of life of patients with
      schizophrenia: an application of the random forest method.
AB  - BACKGROUND: Interpretation of quality of life (QoL) scores over time can be
      difficult because of possible changes in internal standards, values, and
      conceptualization of QoL by individuals. This effect is called a response shift
      (RS). The purpose of this study was to examine whether an RS effect occurred over
      a 24-mo period in patients who were suffering from schizophrenia. METHODS: The
      random forest method was applied to detect any RS reprioritization in a
      multicenter cohort study. QoL was recorded using a generic questionnaire (SF36)
      at baseline (T0), 12 mo (T12), and 24 mo (T24). Patients were categorized into 3
      groups based on psychotic symptoms and relapse (stable, improved, and worsened
      groups) from their clinical profiles. The random forest method was performed to
      predict the General Health score of the SF36 from the other QoL domain scores of
      the SF36. We estimated the average variable importance of the QoL domain for each
      of the 3 groups. RESULTS: A total of 124 (53.2%) patients were defined as stable,
      59 (25.3%) as improved, and 50 (21.5%) as worsened. Among the stable group, the
      Social Functioning domain became more important over time. Of those classified as
      improved, the Mental Health domain became more important over time, while the
      Vitality domain became less important. Among those in the group who worsened, the
      Mental Health domain became less important while the Vitality and Bodily Pain
      domains became more important. CONCLUSIONS: Our study identified differential RS
      reprioritization among patients with different clinical profiles. Further work is
      needed to determine whether RS should be interpreted as a measurement bias or as
      an effect integrated in a true change.

PMID- 25398624
TI  - Human cell line-dependent WC-Co nanoparticle cytotoxicity and genotoxicity: a key
      role of ROS production.
AB  - Although tungsten carbide-cobalt (WC-Co) nanoparticles (NPs) have been widely
      used because of their robustness, their risk to human health remains poorly
      studied, despite the International Agency for Research on Cancer (IARC)
      classifying them as "probably carcinogenic" for humans (Group 2A) in 2006. Our
      current study aimed at defining the cytotoxicity and genotoxicity of one set of
      commercially available 60-nm diameter WC-Co NPs on three human cell lines
      representative of potential target organs: A549 (lung), Hep3B (liver), and Caki-1
      (kidney). The cytotoxicity of WC-Co NPs was determined by evaluating cell
      impedance (xCELLigence), cell survival/death, and cell cycle checkpoints. Flow
      cytometry was used to not only evaluate cell cycle checkpoints, but to also
      estimate reactive oxygen species (ROS) generation. In addition, gamma-H2Ax foci
      detection (confocal microscopy), considered to be the most sensitive technique
      for studying DNA double-strand breaks, was utilized to evaluate genotoxicity. As
      a final part of this study, we assessed the cellular incorporation of WC-Co NPs,
      first byflow cytometry (side scatter), and then by confocal microscopy (light
      reflection) to ensure that the NPs had entered cells. Overall, our current
      findings demonstrate that WC-Co NPs induce cell mortality, DNA double-strand
      breaks, and cell cycle arrest in human renal (Caki-1) and liver (Hep3B) cell
      lines, but do not induce significant cytotoxic effects in A549 lung cells.
      Interestingly, although WC-Co NPs effectively entered the cells in all 3 lines
      tested, ROS were detected in Caki-1 and Hep3B, but not in A549. This may explain
      the great differences in the cytotoxic and genotoxic effects we observed between
      these lines. 

PMID- 25398625
TI  - Identification of Critical Congenital Heart Disease in Vermont: The Role of
      Universal Pulse Oximetry Screening in a Rural State.
AB  - OBJECTIVE: Pulse oximetry screening (POS) is becoming the standard of care in
      screening for critical congenital heart disease (CCHD). Our objective was to
      characterize the historical diagnostic pattern in a rural tertiary care
      children's hospital and explore how universal POS might affect morbidity,
      mortality, and care delivery. PATIENTS AND METHODS: We identified patients <6
      months of age in the Vermont Children's Hospital echocardiogram database with
      CCHD diagnosed between 2002 and 2011. Charts were reviewed to characterize timing
      of diagnosis, course, and outcome. The medical examiner was consulted to identify
      deaths due to undetected CCHD during the study period. RESULTS: Of 60 329 live
      births, 73 (0.12 %) were diagnosed with CCHD. Of these, 31 (42%) were diagnosed
      prenatally, 34 (47%) were diagnosed by clinical examination in the nursery, 7
      (9.6%) were diagnosed after nursery discharge, and 1 (1.4%) was born at home. The
      8 patients not diagnosed by prenatal ultrasound or in the nursery were considered
      cases of undetected CCHD. Three had normal oxygen saturation (>95%) at diagnosis.
      Three presented with cardiovascular compromise. None died and all were well at
      the most recent follow-up. Review of autopsy reports from patients <6 months
      found no deaths from undetected CCHD during the study period. CONCLUSIONS: Over a
      10-year period at our institution, universal POS could have identified 5 patients
      with undetected CCHD, possibly avoiding the need for resuscitation in 3.
      Examination of local diagnostic data may affect the cost/benefit considerations
      of universal POS initiatives in a setting of limited healthcare resources.

PMID- 25398626
TI  - Bruising in Children: Practice Patterns of Pediatric Hematologists and Child
      Abuse Pediatricians.
AB  - The evaluation for children with bruising may be affected by the specialty to
      which they are referred. We conducted a 3-year retrospective review of subjects
      referred for bruising to Child Abuse Pediatrics (CAP) or Pediatric Hematology to
      identify characteristics associated with referral to each specialty and to
      compare the diagnostic evaluations and diagnoses based on specialty. Of 369
      subjects, 275 were referred to CAP and 94 to Hematology. Clinical exam findings
      were similar in both groups. Hematology referrals were significantly more likely
      to have laboratory evaluations. Among those referred to CAP, 9.5% had head
      computed tomography scans and 27.3% had skeletal surveys. No children referred to
      Hematology had these imaging studies performed. Hematology never diagnosed child
      physical abuse, and CAP never diagnosed bleeding disorders. Pediatric
      hematologists and CAPs perform different evaluations and reach different
      diagnostic conclusions for similar patients with bruising. Further investigation
      of these practice patterns is warranted. 

PMID- 25398627
TI  - Pediatric Hypertension Specialists' Perspectives About Adolescent Hypertension
      Management: Implications for Primary Care Providers.
AB  - BACKGROUND: The current specialty-centric hypertension paradigm is unsustainable
      given the high prevalence of primary hypertension in adolescents. OBJECTIVE: To
      describe specialists' perspectives on referral and comanagement for adolescents
      with hypertension. METHODS: Cross-sectional mailed survey of a national sample of
      397 pediatric cardiologists and 389 pediatric nephrologists, conducted January to
      May 2014. RESULTS: Response rate was 61%. Both specialties agreed that primary
      care providers can make the hypertension diagnosis, try lifestyle changes, and
      comanage monitoring of patient blood pressure control and medication side
      effects, but they felt antihypertensive medication use should mainly occur in the
      specialty setting. CONCLUSIONS: Our study suggests specialist support for
      changing the hypertension paradigm to encourage primary care providers, in
      collaboration with specialists, to diagnose hypertension, initiate lifestyle
      changes, and monitor progress and side effects. Future work should focus on
      supporting primary care physician comanagement of adolescents with hypertension.

PMID- 25398628
TI  - How evolution of genomes is reflected in exact DNA sequence match statistics.
AB  - Genome evolution is shaped by a multitude of mutational processes, including
      point mutations, insertions, and deletions of DNA sequences, as well as segmental
      duplications. These mutational processes can leave distinctive qualitative marks
      in the statistical features of genomic DNA sequences. One such feature is the
      match length distribution (MLD) of exactly matching sequence segments within an
      individual genome or between the genomes of related species. These have been
      observed to exhibit characteristic power law decays in many species. Here, we
      show that simple dynamical models consisting solely of duplication and mutation
      processes can already explain the characteristic features of MLDs observed in
      genomic sequences. Surprisingly, we find that these features are largely
      insensitive to details of the underlying mutational processes and do not
      necessarily rely on the action of natural selection. Our results demonstrate how
      analyzing statistical features of DNA sequences can help us reveal and quantify
      the different mutational processes that underlie genome evolution. 

PMID- 25398630
TI  - Development and testing of an objective structured clinical exam (OSCE) to assess
      socio-cultural dimensions of patient safety competency.
AB  - BACKGROUND: Patient safety (PS) receives limited attention in health professional
      curricula. We developed and pilot tested four Objective Structured Clinical
      Examination (OSCE) stations intended to reflect socio-cultural dimensions in the
      Canadian Patient Safety Institute's Safety Competency Framework. SETTING AND
      PARTICIPANTS: 18 third year undergraduate medical and nursing students at a
      Canadian University. METHODS: OSCE cases were developed by faculty with clinical
      and PS expertise with assistance from expert facilitators from the Medical
      Council of Canada. Stations reflect domains in the Safety Competency Framework
      (ie, managing safety risks, culture of safety, communication). Stations were
      assessed by two clinical faculty members. Inter-rater reliability was examined
      using weighted kappa values. Additional aspects of reliability and OSCE
      performance are reported. RESULTS: Assessors exhibited excellent agreement
      (weighted kappa scores ranged from 0.74 to 0.82 for the four OSCE stations).
      Learners' scores varied across the four stations. Nursing students scored
      significantly lower (p<0.05) than medical students on three stations (nursing
      student mean scores=1.9, 1.9 and 2.7; medical student mean scores=2.8, 2.9 and
      3.5 for stations 1, 2 and 3, respectively where 1=borderline unsatisfactory,
      2=borderline satisfactory and 3=competence demonstrated). 7/18 students (39%)
      scored below 'borderline satisfactory' on one or more stations. CONCLUSIONS:
      Results show (1) four OSCE stations evaluating socio-cultural dimensions of PS
      achieved variation in scores and (2) performance on this OSCE can be evaluated
      with high reliability, suggesting a single assessor per station would be
      sufficient. Differences between nursing and medical student performance are
      interesting; however, it is unclear what factors explain these differences.

PMID- 25398629
TI  - Species-specific exon loss in human transcriptomes.
AB  - Changes in exon-intron structures and splicing patterns represent an important
      mechanism for the evolution of gene functions and species-specific regulatory
      networks. Although exon creation is widespread during primate and human evolution
      and has been studied extensively, much less is known about the scope and
      potential impact of human-specific exon loss events. Historically, transcriptome
      data and exon annotations are significantly biased toward humans over nonhuman
      primates. This ascertainment bias makes it challenging to discover human-specific
      exon loss events. We carried out a transcriptome-wide search of human-specific
      exon loss events, by taking advantage of RNA sequencing (RNA-seq) as a powerful
      and unbiased tool for exon discovery and annotation. Using RNA-seq data of
      humans, chimpanzees, and other primates, we reconstructed and compared transcript
      structures across the primate phylogeny. We discovered 33 candidate human
      specific exon loss events, among which six exons passed stringent experimental
      filters for the complete loss of splicing activities in diverse human tissues.
      These events may result from human-specific deletion of genomic DNA, or small
      scale sequence changes that inactivated splicing signals. The impact of human
      specific exon loss events is predominantly regulatory. Three of the six events
      occurred in the 5' untranslated region (5'-UTR) and affected cis-regulatory
      elements of mRNA translation. In SLC7A6, a gene encoding an amino acid
      transporter, luciferase reporter assays suggested that both a human-specific exon
      loss event and an independent human-specific single nucleotide substitution in
      the 5'-UTR increased mRNA translational efficiency. Our study provides novel
      insights into the molecular mechanisms and evolutionary consequences of exon loss
      during human evolution. 

PMID- 25398631
TI  - Protective effects of three remote ischemic conditioning procedures against renal
      ischemic/reperfusion injury in rat kidneys: a comparative study.
AB  - BACKGROUND: Remote ischemic perconditioning (RIPerC), remote ischemic
      postconditioning (RIPostC), and remote ischemic perconditioning +
      postconditioning (RIPerC + RIPostC) protect against renal ischemia reperfusion
      injury (IRI). However, the most beneficial approach among these is not known.
      AIMS: To compare the protective effects and study the mechanisms of three
      different remote ischemic conditioning in preventing IRI in the rat kidney.
      METHODS: Fifty healthy adult male Sprague-Dawley rats were randomly assigned to
      five groups: sham, IRI, RIPerC, RIPostC, and RIPerC + RIPostC. Right nephrectomy
      was performed initially in all rats. IRI was induced by occluding the left renal
      artery for 60 min, followed by reperfusion for 24 h. RIPerC, RIPostC, and RIPerC
      + RIPostC were induced with 5-min ischemia/reperfusion (I/R) cycles using a
      tourniquet on the right hind limb. RESULTS: The IRI group showed significant
      serologic evidence of renal injury compared to the sham group (P < 0.05). The
      RIPerC, RIPostC, and RIperC + RIpostC groups displayed significantly lower levels
      of renal dysfunction than the IRI group (P < 0.05). Superoxide dismutase (SOD)
      levels were significantly lower in the IRI group than in the sham group (P =
      0.003), but were significantly less depressed in the RIPerC, RIPostC, and RIperC
      + RIpostC groups (P < 0.05). The IRI group displayed more severe renal tubular
      injury than the RIPerC, RIPostC, and RIPerC + RIPostC groups (P < 0.05).
      CONCLUSION: All three remote ischemic conditioning showed similar therapeutic
      potential for preventing renal IRI. The RIPerC + RIPostC protocol did not show an
      additive effect from the combination of preconditioning and postconditioning. The
      protective mechanism may be due to the stimulation of endogenous antioxidant
      activity by transient limb ischemia-reperfusion.

PMID- 25398632
TI  - Acclimation of leaf cohorts expanded under light and water stresses: an adaptive
      mechanism of Eucryphia cordifolia to face changes in climatic conditions?
AB  - Eucryphia cordifolia Cav. is a long-lived evergreen tree species, commonly found
      as a canopy emergent tree in the Chilean temperate rain forest. This species
      displays successive leaf cohorts throughout the entire growing season. Thus, full
      leaf expansion occurs under different environmental conditions during growing
      such as air temperature, vapor pressure deficit and the progress of moderate
      water stress (WS). These climate variations can be reflected as differences in
      anatomical and physiological characteristics among leaf cohorts. Thus, we
      investigated the potential adaptive role of different co-existing leaf cohorts in
      seedlings grown under shade, drought stress or a combination of the two.
      Photosynthetic and anatomical traits were measured in the first displayed leaf
      cohort and in a subsequent leaf cohort generated during the mid-season. Although
      most anatomical and photosynthetic pigments did not vary between cohorts,
      photosynthetic acclimation did occur in the leaf cohort and was mainly driven by
      biochemical processes such as leaf nitrogen content, Rubisco carboxylation
      capacity and maximal Photosystem II electron transport rather than CO2 diffusion
      conductance. Cohort acclimation could be relevant in the context of climate
      change, as this temperate rainforest will likely face some degree of summer WS
      even under low light conditions. We suggest that the acclimation of the
      photosynthetic capacity among current leaf cohorts represents a well-tuned
      mechanism helping E. cordifolia seedlings to face a single stress like shade or
      drought stress, but is insufficient to cope with simultaneous stresses. 

PMID- 25398633
TI  - The uniqueness of the human dentition as forensic evidence: a systematic review
      on the technological methodology.
AB  - The uniqueness of human dentition is routinely approached as identification
      evidence in forensic odontology. Specifically in bitemark and human
      identification cases, positive identifications are obtained under the hypothesis
      that two individuals do not have the same dental features. The present study
      compiles methodological information from articles on the uniqueness of human
      dentition to support investigations into the mentioned hypothesis. In April 2014,
      three electronic library databases (SciELO(r), MEDLINE(r)/PubMed(r), and
      LILACS(r)) were systematically searched. In parallel, reference lists of relevant
      studies were also screened. From the obtained articles (n = 1235), 13 full-text
      articles were considered eligible. They were examined according to the studied
      parameters: the sample size, the number of examined teeth, the registration
      technique for data collection, the methods for data analysis, and the study
      outcomes. Six combinations of studied data were detected: (1) dental shape, size,
      angulation, and position (n = 1); (2) dental shape, size, and angulation (n = 4);
      (3) dental shape and size (n = 5); (4) dental angulation and position (n = 2);
      (5) dental shape and angulation (n = 1); and (6) dental shape (n = 1). The sample
      size ranged between 10 and 1099 human dentitions. Ten articles examined the six
      anterior teeth, while three articles examined more teeth. Four articles
      exclusively addressed three-dimensional (3D) data registration, while six
      articles used two-dimensional (2D) imaging. In three articles, both imaging
      registrations were combined. Most articles (n = 9) explored the data using
      landmark placement. The other articles (n = 4) comprised digital comparison of
      superimposed dental contours. Although there were large methodological variations
      within the investigated articles, the uniqueness of human dentition remains
      unproved. 

PMID- 25398634
TI  - Suicide drowning in the non-coastal territory of Milan.
AB  - INTRODUCTION: A cadaver in water sets a relevant issue for the forensic
      pathologist, concerning the differential diagnosis between homicide, suicide,
      accidental event, and natural death in water. In the present study, the drowning
      suicides in a non-coastal territory are analyzed, discussing the main diagnostic
      difficulties, the preventive intervention, and the strategies for outlining the
      profile of a "mean victim" that is at risk of committing suicide by drowning.
      METHODS: The cases of drowning suicide were extrapolated by the database of the
      21,472 autopsies performed at the Civic Morgue of Milan, in the period between
      1993 and 2013. RESULTS: Drowning represents the fifth cause of suicide registered
      in Milan for the study period, with 139 cases (3.8% of all suicides). Victims
      were mainly elderly males (61-80 years old) with a history of psychiatric
      diseases in pharmacological therapy; they committed suicide mainly during summer,
      in the rivers. The diatoms test was positive in 82 cases (59%) and highlighted
      typical taxa of fresh water. Alcohol and illicit drugs were not noticed, at high
      levels. CONCLUSION: Drowning suicide occurs even in a non-coastal territory, far
      from the sea, if there is an easy access to the water: specifically, many natural
      and artificial waterways in the Milan district represent a high-risk factor
      predisposing the drowning suicide.

PMID- 25398635
TI  - CT evaluation of timing for ossification of the medial clavicular epiphysis in a
      contemporary Western Australian population.
AB  - The clavicle is the first bone to ossify in the developing embryo and the last to
      complete epiphyseal union. It is the latter sustained period of growth that has
      attracted the interest of skeletal biologists and forensic practitioners alike,
      who collectively recognize the important opportunity this bone affords to
      estimate skeletal age across the prenatal to early adult lifespan. Current
      research is largely directed towards evaluating the applicability of assessing
      fusion in the medial epiphysis, specifically for determining age of majority in
      the living. This study aims to contribute further insights, and inform
      medicolegal practice, by evaluating the Schmeling five-stage system for the
      assessment of clavicular development in a Western Australian population. We
      retrospectively evaluated high-resolution multiple detector computed tomography
      (MDCT) scans of 388 individuals (210 male; 178 female) between 10 and 35 years of
      age. Scans are viewed in axial and multiplanar reconstructed (MPR) images using
      OsiriX(r). Fusion status is scored according to a five-stage system. Transition
      analysis is used to calculate age ranges and determine the mean age for
      transition between an unfused, fusing and fused status. The maximum likelihood
      estimates (in years) for transition from unfused to fusing is 20.60 (male) and
      19.19 (female); transition from fusing to complete fusion is 21.92 (male) and
      21.47 (female). Results of the present study confirm the reliability of the
      assessed method and demonstrate remarkable consistency to data reported for other
      global populations.

PMID- 25398636
TI  - Molecular identification of fungi found on decomposed human bodies in forensic
      autopsy cases.
AB  - To investigate which fungi can be found during forensic autopsies, a PubMed
      literature review was done in regard to fungal growth on decomposed human bodies.
      Unfortunately, the existing data is limited and not all fungi were identified to
      the species level. We, therefore, collected skin samples with macroscopically
      visible fungal growth from 23 autopsy cases in Germany and identified the fungi
      to the species level by molecular methods. The identified species included
      Aspergillus fumigatus and Candida albicans, which pose an allergenic risk,
      especially to persons with underlying lung diseases. Because safety standards are
      lacking, we recommend the use of respiratory protection during exhumations and
      forensic autopsies, when fungal growth is noted. With regard to the future, a
      database was set up which could possibly be used as a forensic tool to determine
      the time of death. 

PMID- 25398637
TI  - Dietary fatty acids affect mitochondrial phospholipid compositions and
      mitochondrial gene expression of rainbow trout liver at different ages.
AB  - Mitochondria are among the first responders to various stressors that challenge
      the homeostasis of cells and organisms. Mitochondrial decay is generally
      associated with impairment in the organelle bioenergetics function and increased
      oxidative stress, and it appears that deterioration of mitochondrial inner
      membrane phospholipids (PL), particularly cardiolipin (CL), and accumulation of
      mitochondrial DNA (mtDNA) mutations are among the main mechanisms involved in
      this process. In the present study, liver mitochondrial membrane PL compositions,
      lipid peroxidation, and mtDNA gene expression were analyzed in rainbow trout fed
      three diets with the same base formulation but with lipid supplied either by fish
      oil (FO), rapeseed oil (RO), or high DHA oil (DHA) during 6 weeks. Specifically,
      two feeding trials were performed using fish from the same population of two ages
      (1 and 3 years), and PL class compositions of liver mitochondria, fatty acid
      composition of individual PL classes, TBARS content, and mtDNA expression were
      determined. Dietary fatty acid composition strongly affected mitochondrial
      membrane composition from trout liver but observed changes did not fully reflect
      the diet, particularly when it contained high DHA. The changes were PL specific,
      CL being particularly resistant to changes in DHA. Some significant differences
      observed in expression of mtDNA with diet may suggest long-term dietary effects
      in mitochondrial gene expression which could affect electron transport chain
      function. All the changes were influenced by fish age, which could be related to
      the different growth rates observed between 1- and 3-year-old trout but that
      could also indicate age-related changes in the ability to maintain structural
      homeostasis of mitochondrial membranes.

PMID- 25398638
TI  - beta-Carotene can reverse dysregulation of iron protein in an in vitro model of
      inflammation.
AB  - Anemia of chronic disease is frequently seen in chronic inflammatory conditions.
      Its hallmark is disrupted iron homeostasis, with increased uptake and retention
      of iron in cells of the reticuloendothelial system. Using the Caco-2 cell line as
      an in vitro model for iron absorption, local intestinal iron-related protein
      dynamics were evaluated during interleukin (IL)1beta/iron-induced inflammation,
      confirmed by IL8 release, and following beta-carotene and vitamin A
      supplementation. Time- and dose-dependent iron administration to the cells was
      then studied. The effects on heavy and light ferritin, ferroportin, transferrin
      receptor and intracellular iron levels were compared in inflamed Caco-2 cells
      with and without application of the anti-inflammatory agents beta-carotene and
      vitamin A. IL1beta treatment led to IL8 release, a surge in both ferritins'
      expressions and suppression of ferroportin and transferrin receptor expression.
      beta-Carotene significantly reduced IL8 (1,306.2-253.75 pg/ml), decreased light
      and heavy ferritin by 77.8 and 45.8%, respectively, and increased ferroportin by
      59.9% (P < 0.05). Increasing iron concentrations and incubation periods resulted
      in increased IL8 release. A strong correlation was found between the levels of
      IL8 and the ferritins. Intracellular iron sequestration was induced by IL1beta
      and iron and alleviated by beta-carotene. beta-Carotene normalized the main iron
      related proteins' levels, reduced IL8 production, and released intracellular
      trapped iron. These results highlight local mucosal control of iron regulation
      and suggest that by applying anti-inflammatory compounds, less iron is locked in
      inflamed intestinal epithelial cells, leading to its increased bioavailability.
      This suggests a possible approach to combating anemia associated with chronic
      inflammatory conditions.

PMID- 25398639
TI  - Predictors of maternal and fetal complications in SLE patients: a prospective
      study.
AB  - The aim of the study was to evaluate predictors of disease flares during
      pregnancy and obstetric and fetal complications in a cohort of systemic lupus
      erythematosus (SLE) patients. One hundred and thirty-two pregnancies in 96 SLE
      patients were prospectively followed by monthly clinical and laboratory
      evaluations. Predictors of lupus flares, fetal and obstetric complications during
      pregnancy were identified performing stepwise logistic regression analysis.
      Maternal lupus flares occurred in 57 % of pregnancies and were being best
      predicted by the number of flares before conception. Manifestations during flares
      were best predicted by the same features occurred before conception:
      dermatological flares by skin rash, renal flares by nephritis, and hematological
      flares by hematological abnormalities. There were 110 live births and 22 fetal
      losses. Among live newborns, 22 % were premature. Fetal loss was best predicted
      by hypertension at conception; miscarriages by the amount of steroids taken
      during the last year before conception; stillbirth by the number of flares during
      the last year before conception; preterm birth by the coexistence of anti
      phospholipid antibody syndrome and anti-double-stranded DNA antibody levels
      before conception; premature rupture of membranes by high ECLAM score during the
      6 months before conception, small for gestation age by hypertension at
      conception; and preeclampsia by positive lupus anticoagulant. Some independent
      predictors of lupus flares and fetal and obstetric complications were identified,
      which can help the risk assessment of pregnancy in SLE patients.

PMID- 25398640
TI  - Autoimmune diagnostics: the technology, the strategy and the clinical governance.
AB  - In recent years, there has been a profound change in autoimmune diagnostics. From
      long, tiring and inaccurate manual methods, the art of diagnostics has turned to
      modern, rapid and automated technology. New antibody tests have been developed,
      and almost all autoimmune diseases now have some specific diagnostic markers. The
      current need to make the most of available economic and human resources has led
      to the production of diagnostic algorithms and guidelines designated for optimal
      strategic use of the tests and to increase the diagnostic appropriateness. An
      important role in this scenario was assumed by the laboratory autoimmunologist,
      whose task is not only to govern the analytical phase, but also to help
      clinicians in correctly choosing the most suitable test for each clinical
      situation and provide consultancy support. In this review, we summarize recent
      advances in technology, describe the diagnostic strategies and highlight the
      current role of the laboratory autoimmunologist in the clinical governance of
      autoimmune diagnostics. 

PMID- 25398641
TI  - Performance of the SMD and SM8 models for predicting solvation free energy of
      neutral solutes in methanol, dimethyl sulfoxide and acetonitrile.
AB  - The continuum solvation models SMD and SM8 were developed using 2,346 solvation
      free energy values for 318 neutral molecules in 91 solvents as reference.
      However, no solvation data of neutral solutes in methanol was used in the
      parametrization, while only few solvation free energy values of solutes in
      dimethyl sulfoxide and acetonitrile were used. In this report, we have tested the
      performance of the models for these important solvents. Taking data from
      literature, we have generated solvation free energy, enthalpy and entropy values
      for 37 solutes in methanol, 21 solutes in dimethyl sulfoxide and 19 solutes in
      acetonitrile. Both SMD and SM8 models have presented a good performance in
      methanol and acetonitrile, with mean unsigned error equal or less than 0.66 and
      0.55 kcal mol(-1) in methanol and acetonitrile, respectively. However, the
      correlation is worse in dimethyl sulfoxide, where the SMD and SM8 methods present
      mean unsigned error of 1.02 and 0.95 kcal mol(-1), respectively. Our results
      point out the SMx family of models need be improved for dimethyl sulfoxide
      solvent.

PMID- 25398642
TI  - Impact on cognitive function-are all statins the same?
AB  - Dementia is a major public health concern, affecting an estimated 7% of the
      population over 65 and 30% over 80 years of age. There is mounting evidence in
      the literature from meta-analyses of high-quality prospective cohort studies that
      statins may have a positive impact in reducing the incidence of dementia. Little
      is known, however, on whether certain types of statins are more impactful than
      others. This narrative review specifically explores the various properties of
      different statin types and whether these differences lead to a clinically
      significant differential impact on cognitive function. We critically evaluate the
      literature, emphasizing interesting and important new findings, and overall aim
      to bring the reader up-to-date on evidence-based recommendations.

PMID- 25398643
TI  - The role of antisense oligonucleotide therapy in patients with familial
      hypercholesterolemia: risks, benefits, and management recommendations.
AB  - Antisense oligonucleotide therapy is a promising approach for the treatment of a
      broad variety of medical conditions. It functions at the cellular level by
      interfering with RNA function, often leading to degradation of specifically
      targeted abnormal gene products implicated in the disease process. Mipomersen is
      a novel antisense oligonucleotide directed at apolipoprotein (apoB)-100, the
      primary apolipoprotein associated with low-density lipoprotein cholesterol (LDL
      C), which has recently been approved for the treatment of familial
      hypercholesterolemia. A number of clinical studies have demonstrated its efficacy
      in lowering LDL-C and apoB levels in patients with elevated LDL-C despite maximal
      medical therapy using conventional lipid-lowering agents. This review outlines
      the risks and benefits of therapy and provides recommendations on the use of
      mipomersen. 

PMID- 25398644
TI  - Statins and delirium: is there a role?
AB  - Delirium is a serious but potentially avoidable complication in critically ill
      patients. Various pathophysiological processes have been associated with delirium
      development; however, neuroinflammation hypothesis and pleiotropic effects are
      the reasons why HMG-CoA reductase inhibitors have been evaluated for delirium
      prevention. Statin therapy is associated with favorable outcomes in critically
      ill patients, but significant variability of results exists in patients who
      received these agents postoperatively. Study design methodological weaknesses,
      inconsistent delirium assessment, and lack of information on sedation regimens
      may have confounded these outcomes. Furthermore, no evidence exists on the type
      of statin, lipophilic or non-lipophilic, that is associated with the most benefit
      or when therapy with a statin should be initiated. Thus, the efficacy of HMGM-CoA
      reductase inhibitors on delirium prevention has not been fully established and
      non-pharmacological methods should remain mainstay of therapy. 

PMID- 25398646
TI  - A description of signals during the first 18 months of the EMA pharmacovigilance
      risk assessment committee.
AB  - BACKGROUND AND OBJECTIVE: New pharmacovigilance legislation in the European Union
      has underlined the importance of signal management, giving the European Medicines
      Agency's newly established Pharmacovigilance Risk Assessment Committee (PRAC) the
      mandate to oversee all aspects of the use of medicinal products including
      detection, assessment, minimization, and communication relating to the risk of
      adverse reactions. In this study, we describe the signals as brought to the PRAC
      during the first 18 months of its operation and the ensuing regulatory actions.
      METHODS: Data were collected from publicly available sources, for the period July
      2012-December 2013, classified according to predefined rules, and described using
      the appropriate descriptive statistics. Suspected adverse drug reactions were
      categorized into the Medical Dictionary for Regulatory Affairs and drug names
      were mapped to the Anatomical Therapeutic Chemical codes. RESULTS: During the
      study period, 125 signals concerning 96 medicinal products were discussed by the
      PRAC. The majority of signals were triggered by spontaneous reports (62%) and the
      median drug age (since marketing authorization) for drugs that prompted a signal
      was 12 years, significantly less compared with drugs that had no signal within
      the same period (20 years). The mean time until a decision was reached by the
      PRAC was 75 days (median 30 days, range 0-273) with 43% of all decisions taken
      during the first meeting. The decisions to start a referral and to send a direct
      healthcare professional communication took the least amount of time [54 days
      (median 27 days, range 0-186) and 51 days (median 0 days, range 0-153)].
      CONCLUSIONS: The importance of spontaneous reporting in signal detection and
      monitoring of safety issues throughout the entire life cycle of a medicinal
      product is confirmed in this study. The amount of time a drug has been on the
      market is correlated with the number of signals detected. The PRAC decision
      making process seems efficient particularly with respect to serious concerns; its
      role in improving signal prioritization and real-time signal management will be
      further clarified in its subsequent years of operation.

PMID- 25398645
TI  - Pathogenesis and management of the diabetogenic effect of statins: a role for
      adiponectin and coenzyme Q10?
AB  - There is growing evidence to suggest that statin therapy is associated with an
      increased risk of incident diabetes. The risk for statin-related diabetes depends
      upon many factors including age, pre-existing diabetic risk, type and potency of
      statin. Several mechanisms have been suggested for the diabetogenic effects of
      statins involving processes that alter islet beta-cell function, resulting in
      impaired glucose metabolism. Recent evidence suggests that the association of
      statin therapy with the development of diabetes may be partly mediated by a
      statin-induced decrease in circulating adiponectin and coenzyme Q10. The
      available evidence suggests the benefit of statins in reducing cardiovascular
      events outweigh the risk of developing diabetes. Moreover, statin therapy does
      not impair glycemic control in diabetic patients. Expert recommendations for the
      use of statins in people at risk of developing diabetes have recently been
      published. However, further research is required to elucidate both the
      association between statin use and incident diabetes as well as underlying
      mechanisms. 

PMID- 25398647
TI  - How are we protecting ourselves from radiation exposure? A nationwide survey.
AB  - PURPOSE: We performed a nationwide survey of Brazilian urologists to study
      behaviors toward radiation exposure and the use of protective and monitoring
      equipment. METHODS: A 13-question e-mail questionnaire was sent to 4,526
      Brazilian urologists; the questions addressed demographic characteristics,
      radiation exposure, and the utilization of shielding devices and dosimeters. The
      reasons why these devices were not used were also investigated. RESULTS: A total
      of 332 completed questionnaires were analyzed (7.3 %); the median age of the
      respondents was 43.3 +/- 10.8 years. Lead aprons and thyroid protection are
      utilized in every procedure by 84.4 and 53.89 % of respondents, respectively.
      Protective eyeglasses are never used by 72.12 % of the respondents. Older
      urologists were more likely not to use adequate protection. Of the urologists who
      responded, 76.42 % never use dosimeters. CONCLUSION: This study shows an
      unsatisfactory utilization of radiation-shielding devices and dosimeters,
      revealing a low compliance to the as low as reasonably achievable principle among
      Brazilian urologists.

PMID- 25398649
TI  - Salicylic acid alleviates cadmium-induced inhibition of growth and photosynthesis
      through upregulating antioxidant defense system in two melon cultivars (Cucumis
      melo L.).
AB  - Cadmium (Cd) is a widespread toxic heavy metal that usually causes deleterious
      effects on plant growth and development. Salicylic acid (SA), a naturally
      existing phenolic compound, is involved in specific responses to various
      environmental stresses. To explore the role of SA in the tolerance of melon
      (Cucumis melo L.) to Cd stress, the influence of SA application on the growth and
      physiological processes was compared in the two melon cultivars Hamilv (Cd
      tolerant) and Xiulv (Cd-sensitive) under Cd stress. Under 400-MUM Cd treatment,
      Hamilv showed a higher biomass accumulation, more chlorophyll (Chl), greater
      photosynthesis, and less oxidative damage compared to Xiulv. Foliar spraying of
      0.1 mM SA dramatically alleviated Cd-induced growth inhibition in the two melon
      genotypes. Simultaneously, SA pretreatment attenuated the decrease in Chl
      content, photosynthetic capacity, and PSII photochemistry efficiency in Cd
      stressed plants. Furthermore, exogenous SA significantly reduced superoxide anion
      production and lipid peroxidation, followed by increase in the activities of
      antioxidant enzyme superoxide dismutase, guaiacol peroxidase, catalase, and
      ascorbate peroxidase, and content of soluble protein and free proline in both the
      genotypes under Cd stress. The effect of SA was more conspicuous in Xiulv than
      Hamilv, reflected in the biomass, photosynthetic pigments, stomatal conductance,
      water use efficiency, and antioxidant enzymes. These results suggest that
      exogenous spray of SA can alleviate the adverse effects of Cd on the growth and
      photosynthesis of both the melon cultivars, mostly through promoting antioxidant
      defense capacity. It also indicates that SA-included protection against Cd damage
      is to a greater extent more pronounced in Cd-sensitive genotype than Cd-tolerant
      genotype.

PMID- 25398650
TI  - The chemokine CXCL9 exacerbates chemotherapy-induced acute intestinal damage
      through inhibition of mucosal restitution.
AB  - PURPOSE: Acute intestinal damage induced by chemotherapeutic agent is often a
      dose-limiting factor in clinical cancer therapy. The aim of this study was to
      investigate the effect of chemokine CXCL9 on the intestinal damage after
      chemotherapy and explore the therapeutic potential of anti-CXCL9 agents. METHODS:
      In vitro cell proliferation assay was performed with a non-tumorigenic human
      epithelial cell line MCF10A. Multiple pathway analysis was carried out to explore
      the pathway that mediated the effect of CXCL9, and the corresponding downstream
      effector was identified with enzyme-linked immunosorbent assays. Chemotherapy
      induced mouse model of intestinal mucositis was prepared by a single injection of
      the chemotherapeutic agent 5-fluorouracil (5-FU). In vivo expression of cxcl9 and
      its receptor cxcr3 in intestinal mucosa after chemotherapy was determined by
      quantitative real-time PCR. Therapeutic treatment with anti-CXCL9 antibodies was
      investigated to confirm the hypothesis that CXCL9 can contribute to the
      intestinal epithelium damage induced by chemotherapy. RESULTS: CXCL9 inhibited
      the proliferation of MCF10A cells by activating phosphorylation of p70 ribosomal
      S6 kinase (p70S6K), which further promotes the secretion of transforming growth
      factor beta (TGF-beta) as the downstream effector. A blockade of phospho-p70S6K
      with inhibitor abolished the effect of CXCL9 on MCF10A cells and reduced the
      secretion of TGF-beta. The expression levels of cxcl9 and cxcr3 were
      significantly up-regulated in intestinal mucosa after 5-FU injection.
      Neutralizing elevated CXCL9 with anti-CXCR9 antibodies successfully enhanced
      reconstitution of intestinal mucosa and improved the survival rate of mice that
      received high-dose chemotherapy. CONCLUSIONS: CXCL9 inhibits the proliferation of
      epithelial cells via phosphorylation of p70S6K, resulting in the excretion of TGF
      beta as downstream mediator. CXCL9/CXCR3 interaction can exacerbate
      chemotherapeutic agent-induced intestinal damage, and anti-CXCL9 agents are
      potential novel therapeutic candidates for promoting mucosal restitution.

PMID- 25398648
TI  - Proteolysis mediated by cysteine cathepsins and legumain-recent advances and cell
      biological challenges.
AB  - Proteases play essential roles in protein degradation, protein processing, and
      extracellular matrix remodeling in all cell types and tissues. They are also
      involved in protein turnover for maintenance of homeostasis and protein
      activation or inactivation for cell signaling. Proteases range in function and
      specificity, with some performing distinct substrate cleavages, while others
      accomplish proteolysis of a wide range of substrates. As such, different cell
      types use specialized molecular mechanisms to regulate the localization of
      proteases and their function within the compartments to which they are destined.
      Here, we focus on the cysteine family of cathepsin proteases and legumain, which
      act predominately within the endo-lysosomal pathway. In particular, recent
      knowledge on cysteine cathepsins and their primary regulator legumain is
      scrutinized in terms of their trafficking to endo-lysosomal compartments and
      other less recognized cellular locations. We further explore the mechanisms that
      regulate these processes and point to pathological cases which arise from detours
      taken by these proteases. Moreover, the emerging biological roles of specific
      forms and variants of cysteine cathepsins and legumain are discussed. These may
      be decisive, pathogenic, or even deadly when localizing to unusual cellular
      compartments in their enzymatically active form, because they may exert
      unexpected effects by alternative substrate cleavage. Hence, we propose future
      perspectives for addressing the actions of cysteine cathepsins and legumain as
      well as their specific forms and variants. The increasing knowledge in non
      canonical aspects of cysteine cathepsin- and legumain-mediated proteolysis may
      prove valuable for developing new strategies to utilize these versatile proteases
      in therapeutic approaches.

PMID- 25398651
TI  - The inhibition of renin-angiotensin system in advanced pancreatic cancer: an
      exploratory analysis in 349 patients.
AB  - PURPOSE: The role of local renin-angiotensin system (RAS) as a target for the
      treatment of pancreatic cancer has been increasingly reported, but the addition
      of candesartan, one of angiotensin system inhibitors (ASIs), to gemcitabine in
      our prospective trial failed to demonstrate activity against pancreatic cancer.
      The aim of this study was to explore subgroups that would benefit from the
      inhibition of RAS by the use of ASIs. METHODS: Consecutive patients with advanced
      pancreatic cancer receiving gemcitabine-based chemotherapy were retrospectively
      studied. Hazard ratios (HRs) for overall survival (OS) and progression-free
      survival (PFS) were estimated by a Cox proportional hazards model. Interactions
      between the use of ASIs and each subgroup were tested. RESULTS: Between 2001 and
      2013, 349 patients received gemcitabine-based chemotherapy for advanced
      pancreatic cancer; 232 were metastatic, 210 received gemcitabine monotherapy, 108
      took ASIs, 166 were never smokers and 188 were diabetic. The median PFS and OS
      were 4.9 and 11.2 months, respectively. When the effects of the use of ASIs were
      evaluated by a Cox proportional hazard model, there were two subgroups with P
      interaction <0.10 both in PFS and OS: never smokers and gemcitabine monotherapy.
      HRs for PFS and OS by the inhibition of RAS were 0.71 (P = 0.021) and 0.68 (P =
      0.014) in never smokers and 0.70 (P = 0.027) and 0.77 (P = 0.124) in patients
      receiving gemcitabine monotherapy. CONCLUSION: The inhibition of RAS in advanced
      pancreatic cancer might improve clinical outcomes in cases without a history of
      smoking or in cases receiving gemcitabine monotherapy.

PMID- 25398652
TI  - Training needs and supports for evidence-based decision making among the public
      health workforce in the United States.
AB  - BACKGROUND: Preparing the public health workforce to practice evidence-based
      decision making (EBDM) is necessary to effectively impact health outcomes. Few
      studies report on training needs in EBDM at the national level in the United
      States. We report competency gaps to practice EBDM based on four U.S. national
      surveys we conducted with the state and local public health workforce between
      2008 and 2013. METHODS: We compared self-reported data from four U.S. national
      online surveys on EBDM conducted between 2008 and 2013. Participants rated the
      importance of each EBDM competency then rated how available the competency is to
      them when needed on a Likert scale. We calculated a gap score by subtracting
      availability scores from importance scores. We compared mean gaps across surveys
      and utilized independent samples t tests and Cohen's d values to compare state
      level gaps. In addition, participants in the 2013 state health department survey
      selected and ranked three items that "would most encourage you to utilize EBDM in
      your work" and items that "would be most useful to you in applying EBDM in your
      work". We calculated the percentage of participants who ranked each item among
      their top three. RESULTS: The largest competency gaps were consistent across all
      four surveys: economic evaluation, communicating research to policymakers,
      evaluation designs, and adapting interventions. Participants from the 2013 state
      level survey reported significantly larger mean importance and availability
      scores (p <0.001, d =1.00, and p <0.001, d = .78 respectively) and smaller mean
      gaps (p <0.01, d = .19) compared to the 2008 survey. Participants most often
      selected "leaders prioritizing EBDM" (67.9%) among top ways to encourage EBDM
      use. "EBDM training for specific areas" was most commonly ranked as important in
      applying EBDM (64.3%). CONCLUSION: Perceived importance and availability of EBDM
      competencies may be increasing as supports for EBDM continue to grow through
      trends in funding, training, and resources. However, more capacity building is
      needed overall, with specific attention to the largest competency gaps. More work
      with public health departments to both situate trainings to boost competency in
      these areas and continued improvements for organizational practices (leadership
      prioritization) are possible next steps to sustain EBDM efforts.

PMID- 25398653
TI  - MRI screening of women with hereditary predisposition to breast cancer:
      diagnostic performance and survival analysis.

PMID- 25398654
TI  - BCRT response to Moller.

PMID- 25398655
TI  - Pathways of cerebrospinal fluid outflow: a deeper understanding of resorption.
AB  - INTRODUCTION: Cerebrospinal fluid (CSF) absorption has long been held to
      predominantly entail drainage into the venous outflow system via the intracranial
      arachnoid granulations. Newer data suggest pathways involving spinal arachnoid
      granulations and lymphatic channels may also make substantial contributions to
      CSF outflow. METHODS: The putative major CSF outflow pathways and their
      proportionate contribution to CSF absorption were reviewed in this article.
      RESULTS: CSF is absorbed and drained in bulk not just through cerebral arachnoid
      granulations (CAG) but also through spinal arachnoid granulations (SAG) and a
      lymphatic pathway involving egress through cranial and spinal nerve sheaths. The
      proportions of CSF that efflux through each of these major pathways have yet to
      be determined with any certainty in humans, though existing evidence (the
      majority of which is derived from animal studies) suggests that lymphatic
      pathways may account for up to 50% of CSF outflow-presumably leaving the CAG and
      SAG to process the balance. CONCLUSION: Knowledge of the CSF pathways holds
      implications for our ability to understand, prognose, and even treat diseases
      related to CSF circulation and so is a matter of considerable relevance to
      neuroradiology and neurology.

PMID- 25398657
TI  - Strabismus surgery and long-term visual outcomes in patients with preadolescent
      onset ocular myasthenia gravis.
AB  - PURPOSE: To investigate long-term strabismus surgical outcomes and visual
      prognosis in preadolescent ocular myasthenia gravis (OMG). METHODS: The medical
      records of all patients with preadolescent onset OMG who underwent strabismus
      surgery were reviewed. Thirteen patients met the study inclusion criteria. The
      main outcomes, including ocular alignment, number of surgeries, and visual acuity
      at final visit were evaluated. Outcomes were considered successful if there were
      <=10 prism diopters (PD) residual horizontal and <=4 PD residual vertical
      deviations at final recorded visit. RESULTS: Among 13 patients, diplopia
      presented in 11 patients (77.8%). Mean age at disease onset was 5.8 +/- 2.7 years
      (range 1 ~ 11), mean age at surgery was 20.5 +/- 11.3 years (range, 2.5 to 36.6
      years), and the time from disease onset to first operation was 14.8 +/- 9.6 years
      (range, 1.5 to 29.6 years). The average length of postoperative follow-up was 4.7
      +/- 6.6 years (range, 0.5 to 18.9 years). Ocular deviation changed more than 15
      PD during stable disease in six patients (46.2%). No patients underwent more than
      two surgeries. Successful results were achieved in nine patients (69.2%) at final
      recorded visit. CONCLUSIONS: In our series, nine patients (69.2%) with OMG could
      obtain good binocular alignment at final visit. Therefore, strabismus surgery can
      be considered in patients with preadolescent onset OMG who have constant angle of
      deviation despite medical treatment.

PMID- 25398656
TI  - Spinal cord ischemia: aetiology, clinical syndromes and imaging features.
AB  - INTRODUCTION: The purpose of this study was to analyse MR imaging features and
      lesion patterns as defined by compromised vascular territories, correlating them
      to different clinical syndromes and aetiological aspects. METHODS: In a 19.8-year
      period, clinical records and magnetic resonance imaging (MRI) features of 55
      consecutive patients suffering from spinal cord ischemia were evaluated. RESULTS:
      Aetiologies of infarcts were arteriosclerosis of the aorta and vertebral arteries
      (23.6%), aortic surgery or interventional aneurysm repair (11%) and aortic and
      vertebral artery dissection (11%), and in 23.6%, aetiology remained unclear.
      Infarcts occurred in 38.2% at the cervical and thoracic level, respectively, and
      49% of patients suffered from centromedullar syndrome caused by anterior spinal
      artery ischemia. MRI disclosed hyperintense pencil-like lesion pattern on T2WI in
      98.2%, cord swelling in 40%, enhancement on post-contrast T1WI in 42.9% and
      always hyperintense signal on diffusion-weighted imaging (DWI) when acquired.
      CONCLUSION: The most common clinical feature in spinal cord ischemia is a
      centromedullar syndrome, and in contrast to anterior spinal artery ischemia,
      infarcts in the posterior spinal artery territory are rare. The exclusively
      cervical location of the spinal sulcal artery syndrome seems to be a likely
      consequence of anterior spinal artery duplication which is observed
      preferentially here.

PMID- 25398658
TI  - Detailed anatomy of the transverse superior fascial expansion of the upper
      eyelid.
AB  - PURPOSE: This study was designed to elucidate the detailed anatomy of the
      transverse superior fascial expansion (TSFE) and its relationship to the superior
      rectus muscle (SRM) and the levator palpebrae superioris (LPS). METHODS: In this
      cohort study, 46 eyes of 23 cadavers were observed macroscopically. Dissection
      from the SRM origin to its insertion was performed, and the width, length, and
      tensile strength of the TSFE were determined. RESULTS: The TSFE was located
      between the LPS and SRM. It originated at the surface of the SRM, 32.75 +/- 4.40
      mm from the origin of the SRM, and extended anteriorly. The TSFE firmly adhered
      to the SRM surface, 1.53 +/- 0.47 mm medially and 1.19 +/- 0.19 mm laterally,
      extended upwards and anteriorly, and inserted to the under surface of the LPS.
      The TSFE width was 6.70 +/- 1.17 mm at the origin site on the SRM surface and
      11.42 +/- 6.70 mm at the insertion site on the LPS under the surface. Its total
      length was 11.67 +/- 0.87 mm medially and 11.55 +/- 0.94 mm laterally The TSFE
      was first encountered 11.49 +/- 1.17 mm laterally and 11.57 +/- 1.27 mm medially
      from the SRM insertion on the SRM's anterior surface. The tensile strength of the
      TSFE was significantly greater than that of the intermuscular fascia between the
      SRM and LPS (9.74 +/- 4.53 N vs 3.02 +/- 1.85 N, P =0.001). CONCLUSIONS: This
      study provides a good understanding of the TSFE structures conducive to
      performing SRM surgery.

PMID- 25398659
TI  - Three-year corneal graft survival rate in high-risk cases treated with
      subconjunctival and topical bevacizumab.
AB  - PURPOSE: To evaluate the effect of combined subconjunctival and topical
      bevacizumab treatment on corneal graft survival rate in high-risk eyes. METHODS:
      Prospective, consecutive, interventional case series. Fifty eyes of 50 high-risk
      patients scheduled for penetrating keratoplasty (PK) were included in the study;
      two Stevens-Johnson syndromes (SJS), five corneal combustions due to chemical
      burn, seven post-traumatic vascularised leucomas, 11 post-infectious vascularised
      leucomas, 19 rejected grafts and six corneal ulcers. Additional surgeries such as
      autologous limbal stem cell and/or amniotic membrane transplantation were
      performed together with PK in ten cases. All eyes received subconjunctival
      injection of 0.5 ml bevacizumab (25 mg/ml) after PK. Eyes with more than two
      quadrants of neovascularisation (NV) received bevacizumab drops (25 mg/ml)
      postoperatively for up to 12 weeks. Donor grafts were followed up for best
      corrected visual acuity, graft clarity, change in NV, endothelial cell density
      loss (ECD), and adverse events. Mean follow-up was 36.5 months (range 32-61).
      RESULTS: Best-corrected visual acuity increase was statistically significant in
      82 % (41/50) of eyes 3 years after PK (paired t-test, p = 0.02). Thirty-five (70
      %) high-risk grafts remained clear throughout the 3-year follow-up period.
      Decrease of corneal NV was observed in 84 % (42/50) of eyes treated with
      bevacizumab. ECD changed from preoperative 2,864 +/- 301 down to 1,905 +/- 187
      cells/mm(2) at 3 postoperative years. A non-healing epithelial defect was
      recorded in one patient with SJS after 12 weeks of topical bevacizumab.
      CONCLUSION: Combined subconjunctival and topical bevacizumab treatment may
      improve corneal graft survival rate in the majority of high-risk cases.

PMID- 25398660
TI  - Evaluation of oxidative stress levels in the conjunctival epithelium of patients
      with or without dry eye, and dry eye patients treated with preservative-free
      hyaluronic acid 0.15 % and vitamin B12 eye drops.
AB  - PURPOSE: Increased levels of oxidative stress have been seen in animal models of
      dry eye and in the conjunctival epithelial cells of patients with Sjogren's
      syndrome. The aims of this study were to compare the levels of oxidative stress
      in patients with dry eye and patients without dry eye and to evaluate the effects
      of treatment with preservative-free eye drops containing hyaluronic acid 0.15 %
      and vitamin B12 on oxidative stress and dry eye symptoms. METHODS: Three cohorts
      of patients who were to undergo planned cataract surgery were enrolled: patients
      with dry eye randomized to either no treatment (n = 29) or treatment (n = 32)
      with hyaluronic acid/vitamin B12 eye drops, and patients without dry eye (n =
      42). Patients were assessed by Schirmer's type I test, fluorescein clearance test
      (FCT), Break Up Time (BUT), and Ocular Surface Disease Index (OSDI). Lipid
      peroxidation, a marker of oxidative stress, was assessed by LP-CHOLOX test.
      RESULTS: Compared with patients without dry eye, patients with dry eye had
      significantly increased levels of oxidative stress, higher OSDI and FCT scores,
      and significantly lower Schirmer's test and BUT scores. Treatment with eye drops
      containing hyaluronic acid 0.15 % and vitamin B12 was associated with
      significantly reduced levels of oxidative stress and OSDI and FCT scores and
      significantly increased Schirmer's test and BUT scores. CONCLUSIONS: These
      findings indicate that oxidative stress is associated with dry eye and that
      hyaluronic acid/vitamin B12 eye drops may attenuate oxidative stress and
      inflammation, improving dry eye symptoms. Further study in controlled clinical
      trials is warranted.

PMID- 25398661
TI  - Astigmatic equivalence of 2.2-mm and 1.8-mm superior clear corneal cataract
      incision.
AB  - PURPOSE: To evaluate the astigmatic effects of 2.2-mm and 1.8-mm cataract
      incisions. METHODS: A randomized prospective study of 190 eyes of 151 patients
      undergoing superior clear corneal incision (SCCI) was divided into three groups:
      61 eyes with a control 3.2-mm SCCI; 66 eyes with a 2.2-mm SCCI; and 63 eyes with
      a 1.8-mm SCCI. The corneal astigmatism was measured with an autokeratometer
      preoperatively and 1 month after surgery. The with-the-wound (WTW), against the
      wound (ATW), and WTW-ATW changes were calculated using the Holladay-Cravy-Koch
      formula. RESULTS: The WTW, ATW, and WTW-ATW changes were significantly higher for
      the control 3.2-mm SCCI than for the 2.2- and 1.8-mm SCCI (all p < 0.001), and no
      difference was found between the 2.2- and 1.8-mm SCCI incision groups.
      CONCLUSION: In our study, the astigmatic effects were the same for the 2.2 mm and
      1.8 mm incisions and as expected, were significantly lower than the control 3.2
      mm incision group.

PMID- 25398662
TI  - Measurement of retinal function with flash electroretinography in Chinese
      patients with hyperlipidemia.

PMID- 25398663
TI  - Conjunctival squamous cell neoplasia: the Liverpool Ocular Oncology Centre
      experience.
AB  - PURPOSE: To report the outcome of patients with conjunctival squamous cell
      neoplasia (CSCN)--including conjunctival squamous cell carcinoma (SCC),
      conjunctival squamous intraepithelial neoplasia (C-SIN) and carcinoma in situ
      (CIS)-treated at the Liverpool Ocular Oncology Centre (LOOC). METHODS: Patients
      treated between January 1993 and September 2011 were identified and categorised
      as having 'primary' or 'salvage' treatment, according to whether they had
      undergone a surgical procedure before referral to our centre. Invasive SCC was
      treated by excision with adjunctive ruthenium plaque radiotherapy. C-SIN or CIS
      was treated with topical 5-fluorouracil (5-FU), and in a few cases, cryotherapy.
      RESULTS: Primary treatment was administered to 20 patients (16 males, four
      females). Mean age was 62 years (range, 33-85). Histological examination revealed
      C-SIN/CIS in ten patients and invasive SCC in nine. Median follow-up was 69
      months (range, 34-168). Three patients required further topical chemotherapy for
      persistent/recurrent C-SIN. Salvage therapy was administered to 21 patients (15
      males, six females). Mean age was 63 years (range, 26-82). Histology showed C
      SIN/CIS in 11 patients and invasive SCC in ten. Median follow-up was 54.5 months
      (range, 36-120). At the close of this audit, there was no recurrence of invasive
      or metastatic disease in either the primary or salvage groups. CONCLUSIONS: Our
      established protocol for treatment of CSCN has proven successful in local tumour
      control, and avoids ocular complications. We advocate adjunctive radiotherapy in
      patients with invasive SCC and chemotherapy in C-SIN/CIS. For improved patient
      outcome, prompt referral to a specialist centre is encouraged.

PMID- 25398664
TI  - Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is
      a putative oncogene in gastric cancer.
AB  - MicroRNAs are found to play an important role in gastric cancer. Reduced
      expression of microRNA-218 (miR-218) is of key interest. The target gene of
      microRNA-218, epidermal growth factor receptor-coamplified and overexpressed
      protein (ECOP) encoded by the VOPP1 gene, has been implicated in tumorigenesis.
      However, few studies on expression and function of ECOP in gastric cancer have
      been reported. ECOP expression was determined in matched normal and gastric
      adenocarcinoma tissue specimens by immunohistochemistry and western blot.
      Subsequently, ectopic overexpression and RNAi-mediated silencing of VOPP1 was
      effected in the human gastric cancer cell line, AGS. Proliferation and migration
      of parental, VOPP1 overexpressing and VOPP1-silenced AGS cells were evaluated by
      cell proliferation assay and scratch wound-healing motility assay. Finally,
      intracellular localization of ECOP in AGS cells was assessed by green fluorescent
      protein tagging and fluorescent microscopy. Western blot and immunohistochemistry
      showed overexpression of ECOP in gastric adenocarcinoma tissues compared to
      matched normal tissue specimens. Ectopic overexpression and RNAi-mediated
      silencing of VOPP1 promoted and inhibited, respectively, cell proliferation and
      migration in AGS cells. Intracellular localization of ECOP in perinuclear
      lysosomes mimicked colocalization earlier reported for other cancerous cells.
      VOPP1 is overexpressed in gastric adenocarcinoma, which is involved in promoting
      cell proliferation and migration and thus might serve as a putative oncogene.

PMID- 25398665
TI  - Rethinking 'Efficacy': Ritual Healing and Trance in the Mahanubhav Shrines in
      India.
AB  - Ritual healing has been one of the core topics in anthropology and, to a lesser
      extent, in psychology as well. Much of the research on ritual healing has focused
      on how healing works, and what factors constitute the efficacy of healing. In
      answering this question, scholars have focused primarily on two main factors-the
      symbolic significance of rituals, and the relationship between the healer and the
      patient. This paper explores understandings about efficacy in a context where
      elaborate rituals do not occur, the role of the healer is minimal, and the
      sufferers do not have expectations of complete wellness. In the Mahanubhav
      temples in India, healing is not understood as the removal of symptoms. The
      healing process involves amplifying unpleasant and painful symptoms, thereby
      'drawing out' the illness from the body. Moreover, the temple narratives
      emphasize the transient nature of temple healing, where people rarely become
      completely well. They therefore frequently return to stay in the temple as and
      when their symptoms recur, thus forging long-term bond with the temple community
      and sect. These findings suggest that temple healing is powerful not so much for
      the practice of specific exorcist rituals, but for providing a refuge and a
      community for suffering individuals. 

PMID- 25398666
TI  - Gender dimorphism and age of onset in malignant peripheral nerve sheath tumor
      preclinical models and human patients.
AB  - BACKGROUND: Gender-based differences in disease onset in murine models of
      malignant peripheral nerve sheath tumor (MPNST) and in patients with
      Neurofibromatosis type-1-(NF-1)-associated or spontaneous MPNST has not been well
      studied. METHODS: Forty-three mGFAP-Cre+;Ptenloxp/+;LSL-K-rasG12D/+ mice were
      observed for tumor development and evaluated for gender disparity in age of MPNST
      onset. Patient data from the prospectively collected UCLA sarcoma database (1974
      2011, n = 113 MPNST patients) and 39 published studies on MPNST patients (n =
      916) were analyzed for age of onset differences between sexes and between NF-1
      and spontaneous MPNST patients. RESULTS: Our murine model showed gender-based
      differences in MPNST onset, with males developing MPNST significantly earlier
      than females (142 vs. 162 days, p = 0.015). In the UCLA patient population, males
      also developed MPNST earlier than females (median age 35 vs. 39.5 years, p =
      0.048). Patients with NF-1-associated MPNST had significantly earlier age of
      onset compared to spontaneous MPNST (median age 33 vs. 39 years, p = 0.007).
      However, expanded analysis of 916 published MPNST cases revealed no significant
      age difference in MPNST onset between males and females. Similar to the UCLA
      dataset, patients with NF-1 developed MPNST at a significantly younger age than
      spontaneous MPNST patients (p < 0.0001, median age 28 vs. 41 years) and this
      disparity was maintained across North American, European, and Asian populations.
      CONCLUSIONS: Although our preclinical model and single-institution patient cohort
      show gender dimorphism in MPNST onset, no significant gender disparity was
      detected in the larger MPNST patient meta-dataset. NF-1 patients develop MPNST 13
      years earlier than patients with spontaneous MPNST, with little geographical
      variance.

PMID- 25398667
TI  - Racial Disparity Among the Head and Neck Cancer Population.
AB  - Head and neck cancer is the ninth most common cancer in the USA, accounting for
      3.3 % of all cancers. The incidence of head and neck cancer has plateaued
      recently; however, morbidity and mortality continue to remain high. Moreover,
      racial disparity between African-American and White patients has been studied in
      the head and neck community, and a vast difference still remains in mortality
      rate and late stage at presentation. A review of the English literature was
      performed using PubMed/MEDLINE for demographics, epidemiology, and studies that
      focused on the disparity in head and neck cancer between African-American and
      White patients. Age-adjusted incidence of head and neck cancer is increased in
      African-Americans, while the 5-year survival is decreased compared to Whites.
      African-American patients present with more advanced disease. When receiving
      similar multidisciplinary care, the overall survival was not significantly
      different, but racial disparity often persists in treatment regimens.
      Socioeconomic determinants such as insurance status play a critical role in
      racial disparity, along with low levels of public awareness, a lack of knowledge
      of specific risk factors, and a sense of mistrust that is seen in the African
      American population. Disparity in the head and neck cancer community is
      worrisome, and although efforts have been taken to decrease the disparity, a
      significant difference exists. Fortunately, the disparity is reversible and can
      be eliminated. To do so, it is critical to extend to underserved community
      programs that provide appropriate screening and diagnosis, with subsequent follow
      up and treatment following the standards of care.

PMID- 25398668
TI  - The evidence for the contribution of the autism susceptibility candidate 2
      (AUTS2) gene in heroin dependence susceptibility.
AB  - The single-nucleotide polymorphisms (SNP) rs6943555 in autism susceptibility
      candidate 2 (AUTS2) has been reported to be significantly associated with alcohol
      consumption in Europeans. In this study, we identified the SNP in AUTS2
      contributing to the genetic susceptibility to heroin dependence. The potential
      association between heroin dependence and 21 SNPs (rs2270162, rs2851510,
      rs513150, rs595681, rs210606, rs10237984, rs13228123, rs10235781, rs6969375,
      rs6943555, rs10251416, rs17141963, rs12669427, rs723340, rs2293507, rs2293508,
      rs6960426, rs9886351, rs2293501, rs10277450, rs1918425) of AUTS2 was examined in
      a Chinese Han population using the MassARRAY system. The participants included
      426 patients with heroin dependence and 416 healthy controls. Single SNP
      association, haplotype association, and clinical phenotype association were
      analyzed. Single SNP association revealed that AA homozygotes of rs6943555 were
      significantly over-represented in the patients with heroin dependence compared
      with the control subjects (P=0.0019). The patients with heroin dependence had a
      significantly higher frequency of the A allele (P=0.0003, odd ratio (OR)=1.429,
      95% confidence interval (CI)=1.175-1.738). Strong linkage disequilibrium (LD) was
      observed in five blocks (D'>0.9). In block 2, significantly more A-A haplotypes
      (P=0.006 after Bonferroni corrections) and significantly fewer T-A haplotypes
      (P=0.040) were found in the patients with heroin dependence. The genotype and
      clinical phenotype correlation study of the rs6943555 carriers showed that the
      amount of heroin self-injection was lower in the patients with the AA genotype
      relative to AT+TT genotypes (P<0.01). Our results confirmed that, in addition to
      heroin consumption, the SNP rs6943555 of AUTS2 may also play an important role in
      the etiology of heroin dependence.

PMID- 25398669
TI  - An unusual course of inferior interventricular artery.

PMID- 25398671
TI  - Understanding the reasons for delayed referral for intrathecal baclofen therapy
      in pediatric patients with severe spasticity.
AB  - OBJECTIVE: Intrathecal baclofen therapy (ITB) has been used in the treatment of
      spasticity and dystonia. In our pediatric movement disorder clinic, we noted a
      delay in referral of patients for consideration of ITB. Often, only after years
      of failed medical therapy, a baclofen pump is considered. This study attempts to
      investigate the prevalence, length and causes of the delay. METHODS: A
      retrospective, outcome analysis was performed. We conducted a survey of 30
      pediatric patients who received baclofen pumps between the ages of 5 and 23.
      Patients were divided into two groups (before and after ITB approval by the US
      Food and Drug Administration in 1996) (FDA/Center for Drug Evaluation and
      Research, 2014; Ridley and Rawlins, J Neurosci Nurs 38:72-82, 2006; Medical
      Advisory Secretariat, Ont Health Technol Assess Ser 5:1-93, 2005). Information
      was collected regarding their onset of spasticity, attempted treatments, pump
      referral, satisfaction, and resulting change in the quality of life. RESULTS:
      There was a delay in referral in most cases investigated. Average time to
      baclofen pump implantation, after initial onset of spasticity, was 5.14 years
      (group A) and 11.7 years (group B). Out of the subjects who reported diminished
      effects or no effect of pharmacological treatment, 93 % of these respondents
      reported that ITB had a dramatic long-lasting effect on their spasticity. Of 30
      patients, 28 reported effectiveness of ITB, and 26 of 30 subjects reported an
      improved quality and ease of life. CONCLUSION: Despite the limitations of this
      subjective retrospective analysis of outcomes and delay in referral, the opinions
      of the parents and caregivers should be considered. Earlier referral for ITB
      therapy may better treat severe spasticity in pediatric patients.

PMID- 25398670
TI  - SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for
      survival of patients with acute myeloid leukemia: an in vitro study.
AB  - BACKGROUND: The mechanism behind poor survival of acute myeloid leukemia (AML)
      patients with 1-barabinofuranosylcytosine (Ara-C) based treatment remains
      unclear. This study aimed to assess the pharmacogenomic effects of Ara-C
      metabolic pathway in patients with AML. METHODS: The genotypes of 19 single
      nucleotide polymorphisms (SNPs) of DCK, CDA and SLC29A1from 100 AML patients
      treated with Ara-C were examined. All the SNPs were screened with ligase
      detection reaction assay. The transcription analysis of genes was examined by
      quantitative real time polymerase chain reaction. The association between
      clinical outcome and gene variants was evaluated by Kaplan-Meier method. RESULTS:
      Genotypes of rs9394992 and rs324148 for SLC29A1 in remission patients were
      significantly different from those in relapsed ones. Post-induction overall
      survival (OS) significantly decreased in patients with the CC genotype of
      rs324148 compared with CT and TT genotypes (hazard ratio [HR] = 2.997 [95%
      confidence interval (CI): 1.71-5.27]). As compared with CT and TT genotype,
      patients with the CC genotype of rs9394992 had longer survival time (HR = 0.25
      [95% CI: 0.075-0.81]; HR = 0.43 [95% CI: 0.24-0.78]) and longer disease-free
      survival (DFS) (HR = 0.52 [95% CI: 0.29-0.93]; HR = 0.15 [95% CI: 0.05-0.47]) as
      well As compared with CT and TT genotype, patients with the CC genotype of
      rs324148 had shorter DFS (HR = 3.18 [95% CI: 1.76-5.76]). Additionally, patients
      with adverse karyotypes had shorter DFS (HR = 0.17 [95% CI: 0.05-0.54]) and OS
      (HR = 0.18 [95% CI: 0.05-0.68]). CONCLUSIONS: AML patients with low activity of
      SLC29A1 genotype have shorter DFS and OS in Ara-C based therapy. Genotypes of
      rs9394992 and rs324148 may be independent prognostic predictors for the survival
      of AML patients.

PMID- 25398672
TI  - Hormone therapy for reproductive depression in women.
AB  - An email survey of patients attending a PMS and Menopause Centre produced 238
      patients whose principal presenting symptom was depression. Seventy-seven percent
      claimed to have had severe or moderate depression, 17% had had at least one
      psychotic episode and 14% had attempted suicide. Fifty-eight percent had seen a
      psychiatrist. Seventy-one percent had received antidepressants and 17% had
      received mood stabilising drugs. Twelve percent had been admitted to a
      psychiatric hospital and 3.8% had received electroconvulsive therapy. Sixty-eight
      percent had premenstrual syndrome as a teenager and 145 women (89%) out of 165
      women who had been pregnant had no depression during pregnancy but 110 (66%)
      developed postnatal depression. Ninety-seven women (58%) who had been pregnant
      had suffered both premenstrual depression and postnatal depression. All were
      treated with transdermal estrogens and 93% also had transdermal testosterone. One
      hundred and seventy-one patients had a uterus and received cyclical progestogen
      to protect the endometrium and 63% of these developed the premenstrual syndrome
      type symptoms of progesterone intolerance during the progestogen days. Thirty
      five percent of patients claimed to be cured and 55% had a considerable
      improvement with estrogen therapy. Only 3.7% reported that there was no
      improvement. For 94%, the hormone therapy was a life-changing event for the
      better. None were worse. Forty patients had hysterectomy and bilateral
      oophorectomy for progesterone intolerance or heavy uterine bleeding and 38
      replied that it was life changing for the better with less or no depression. It
      is concluded that premenstrual and postnatal depressions appear in the same
      vulnerable women. These women are typically well during pregnancy and are a sub
      group of reproductive depression which also develops climacteric depression in
      the transition phase. These types of depression are the product of hormonal
      changes and respond well to transdermal hormone therapy. 

PMID- 25398673
TI  - Voiding difficulties in the elderly.
AB  - Voiding difficulties are more common in the elderly. This occurs because of
      physiological changes such as replacement of muscle fibres with collagen, from
      life effect insults such as the effects of childbirth, lead to a reduction in
      contractility and changes in the nerve supply from cholinergic to NANC fibres
      lead to a change in sensation leading to a delay in first sensation. Symptoms are
      often similar to those of overactive bladder and the history in older women
      should include those of hesitancy and poor flow. Likewise, the diagnosis should
      be considered in women presenting with recurrent urinary tract infections. A
      failure to consider voiding difficulties can precipitate a crisis and simple
      strategies such as teaching self-catheterization and using estrogen cream may
      prevent problems occurring. When acute problems occur, catheterization is
      required and a review of precipitating factors may identify medications
      contributing to the condition. The mainstay for treatment, however, remains
      draining with an indwelling catheter or clean intermittent clean catheterisation.

PMID- 25398674
TI  - Umeclidinium/vilanterol: a review of its use as maintenance therapy in adults
      with chronic obstructive pulmonary disease.
AB  - Umeclidinium/vilanterol (Anoro((r)) ElliptaTM; LaventairTM) is an inhaled fixed
      dose combination of a long-acting muscarinic receptor antagonist and a long
      acting beta2-adrenoceptor agonist. It is available in several countries,
      including Japan, the USA, Canada and those of the EU, where it is indicated for
      oral inhalation in adults with chronic obstructive pulmonary disease (COPD).
      Umeclidinium/vilanterol is administered once daily using the ElliptaTM multi-dose
      dry powder inhaler, which is regarded as easy to use. Umeclidinium/vilanterol
      (62.5/25 ug once daily, equivalent to a delivered dose of 55/22 ug once daily)
      was effective and well tolerated in adult patients with COPD participating in
      large, multicentre trials of up to 24 weeks' duration. Umeclidinium/vilanterol
      improved pulmonary function to a significantly greater extent than placebo and
      each of the individual components. Moreover, umeclidinium/vilanterol was
      significantly more effective than once-daily tiotropium bromide monotherapy and a
      twice-daily fixed combination of salmeterol/fluticasone propionate at improving
      pulmonary function. Umeclidinium/vilanterol also had beneficial effects on
      dyspnoea, use of rescue medication, exacerbations, health-related quality of life
      and, in one study, exercise endurance. Umeclidinium/vilanterol is generally well
      tolerated in patients with COPD, with the most common adverse events in clinical
      trials being headache and nasopharyngitis. Umeclidinium/vilanterol was not
      associated with a clinically relevant increased risk of cardiovascular adverse
      events in patients with COPD, when data from several clinical trials were pooled.
      Thus, inhaled umeclidinium/vilanterol extends the treatment options currently
      available for the maintenance treatment of adults with COPD and has the
      convenience of once-daily administration. 

PMID- 25398675
TI  - Risk factors for and perinatal outcomes of major depression during pregnancy: a
      population-based analysis during 2002-2010 in Finland.
AB  - OBJECTIVES: To identify risk factors for and the consequences (several adverse
      perinatal outcomes) of physician-diagnosed major depression during pregnancy
      treated in specialised healthcare. DESIGN: A population-based cross-sectional
      study. SETTING: Data were gathered from Finnish health registers for 1996-2010.
      PARTICIPANTS: All singleton births (n=511,938) for 2002-2010 in Finland. PRIMARY
      OUTCOME MEASURES: Prevalence, risk factors and consequences of major depression
      during pregnancy. RESULTS: Among 511,938 women, 0.8% experienced major depression
      during pregnancy, of which 46.9% had a history of depression prior to pregnancy.
      After history of depression, the second strongest associated factor for major
      depression was fear of childbirth, with a 2.6-fold (adjusted OR (aOR=2.63, 95% CI
      2.39 to 2.89) increased prevalence. The risk profile of major depression also
      included adolescent or advanced maternal age, low or unspecified socioeconomic
      status (SES), single marital status, smoking, prior pregnancy terminations,
      anaemia and gestational diabetes regardless of a history of depression. Outcomes
      of pregnancies were worse among women with major depression than without. The
      contribution of smoking was substantial to modest for small-for-gestational age
      newborn (<-2 SD below mean birth), low birth weight (<2500 g), preterm birth (<37
      weeks) and admission to neonatal intensive care associated with major depression,
      whereas SES made only a minor contribution. CONCLUSIONS: Physician-diagnosed
      major depression during pregnancy was found to be rare. The strongest risk factor
      was history of depression prior to pregnancy. Other associated factors were fear
      of childbirth, low SES, lack of social support and unhealthy reproductive
      behaviour such as smoking. Outcomes of pregnancies were worse among women with
      major depression than without. Smoking during pregnancy made a substantial to
      modest contribution to adverse outcomes associated with depression during
      pregnancy.

PMID- 25398676
TI  - A population-based observational study of diabetes during pregnancy in Victoria,
      Australia, 1999-2008.
AB  - OBJECTIVES: This paper reports secular trends in diabetes in pregnancy in
      Victoria, Australia and examines the effect of including or excluding women with
      pre-existing diabetes on gestational diabetes (GDM) prevalence estimates. DESIGN:
      Population-based observational study. SETTING: All births in Victoria, Australia
      between 1999 and 2008 PARTICIPANTS: 634,932 pregnancies resulting in a birth
      registered with the Victorian Perinatal Data Collection OUTCOME MEASURES: Crude
      and age-standardised secular trends in pre-existing diabetes and GDM prevalence;
      secular GDM trends by maternal birthplace; effects on GDM prevalence of including
      and excluding pre-existing diabetes from the denominator. RESULTS: Of the 634,932
      pregnancies, 2954 (0.5%) occurred in women with pre-existing diabetes and 29,147
      (4.6%) were complicated by GDM. Mean maternal age increased from 29.7 years in
      1999 to 30.8 years in 2008. GDM prevalence increased in most maternal age groups.
      In 2008, age-standardised GDM prevalence was 31% higher than in 1999; secular
      increases were greater for Australian-born non-Indigenous (29% increase) than
      immigrant women (12.3% increase). The annual number of pregnancies in women with
      pre-existing diabetes almost doubled from 1999 to 2008 and prevalence increased
      from 0.4% to 0.6%. However, including or excluding pre-existing diabetes had
      little effect on GDM prevalence estimates. CONCLUSIONS: Pre-existing diabetes and
      GDM prevalence increased in Victoria between 1999 and 2008 and rising maternal
      age does not fully explain these trends. These findings have important
      implications for preventive initiatives. Including or excluding small numbers of
      women with pre-existing diabetes resulted in minimal changes in GDM estimates. As
      pre-existing diabetes in young women increases, this methodological issue will
      likely become important.

PMID- 25398677
TI  - Patients with nodding syndrome in Uganda improve with symptomatic treatment: a
      cross-sectional study.
AB  - OBJECTIVES: Nodding syndrome (NS) is a poorly understood neurological disorder
      affecting thousands of children in Africa. In March 2012, we introduced a
      treatment intervention that aimed to provide symptomatic relief. This
      intervention included sodium valproate for seizures, management of behaviour and
      emotional difficulties, nutritional therapy and physical rehabilitation. We
      assessed the clinical and functional outcomes of this intervention after 12
      months of implementation. DESIGN: This was a cross-sectional study of a cohort of
      patients with NS receiving the specified intervention. We abstracted
      preintervention features from records and compared these with the current
      clinical status. We performed similar assessments on a cohort of patients with
      other convulsive epilepsies (OCE) and compared the outcomes of the two groups.
      PARTICIPANTS: Participants were patients with WHO-defined NS and patients with
      OCE attending the same centres. OUTCOME MEASURES: The primary outcome was the
      proportion of patients with seizure freedom (>=1 month without seizures).
      Secondary outcome measures included a reduction in seizure frequency, resolution
      of behaviour and emotional difficulties, and independence in basic self-care.
      RESULTS: Patients with NS had had a longer duration of symptoms (median 5 (IQR 3,
      6) years) compared with those with OCE (4 (IQR 2, 6) years), p<0.001. The
      intervention resulted in marked improvements in both groups; compared to the
      preintervention state, 121/484 (25%) patients with NS achieved seizure freedom
      and there was a >70% reduction in seizure frequency; behaviour and emotional
      difficulties resolved in 194/327 (59%) patients; 193/484 (40%) patients had
      enrolled in school including 17.7% who had earlier withdrawn due to severe
      seizures, and over 80% had achieved independence in basic self-care. These
      improvements were, however, less than that in patients with OCE of whom 243/476
      (51.1%) patients were seizure free and in whom the seizure frequency had reduced
      by 86%. CONCLUSIONS: Ugandan children with NS show substantial clinical and
      functional improvements with symptomatic treatments suggesting that NS is
      probably a reversible encephalopathy.

PMID- 25398678
TI  - Pre-existing atrial fibrillation and risk of arterial thromboembolism and death
      following pneumonia: a population-based cohort study.
AB  - OBJECTIVES: To examine the effect of pre-existing atrial fibrillation (AF) and
      associated therapy on the risk of arterial thromboembolism (ATE) and death
      following pneumonia. DESIGN, SETTING AND PARTICIPANTS: Population-based cohort
      study (1997-2012) of 88,315 patients with first-time hospitalisation with
      pneumonia in Northern Denmark. RESULTS: Of the included patients (median age 73.4
      years), 8880 (10.1%) had pre-existing AF. The risk of ATE within 30 days of
      admission was 5.2% in patients with AF and 3.6% in patients without AF. After
      adjustment for higher age and comorbidity, the adjusted HR (aHR) with AF was 1.06
      (95% CI 0.96 to 1.18). Among patients with AF, reduced risk of ATE was observed
      in vitamin-K antagonist users compared with non-users (aHR 0.74 (95% CI 0.61 to
      0.91)). Thirty-day mortality was 20.1% in patients with AF and 13.9% in patients
      without AF. Corresponding 1-year mortalities were 43.7% and 30.3%. The aHRs for
      30-day and 1-year mortality with AF were 1.00 (95% CI 0.94 to 1.05) and 1.01 (95%
      CI 0.98 to 1.05). In patients with AF, reduced mortality risk was observed in
      users of vitamin-K antagonists (aHR 0.70 (95% CI 0.63 to 0.77)) and beta-blockers
      (aHR 0.77 (95% CI 0.70 to 0.85). Increased mortality was found in digoxin users
      (aHR 1.16 (95% CI 1.06 to 1.28)). CONCLUSIONS: Pre-existing AF is frequent in
      patients hospitalised with pneumonia and a marker of increased risk of ATE and
      death, explained by higher patient age and comorbidity. Prognosis is closely
      related to preadmission medical treatment for AF.

PMID- 25398679
TI  - Exposure to sodium channel-inhibiting drugs and cancer survival: protocol for a
      cohort study using the QResearch primary care database.
AB  - INTRODUCTION: Metastasis from solid tumours is associated with significant
      morbidity and mortality, and is the leading cause of cancer-related deaths.
      Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of
      epilepsy. VGSCs are also present in cancer cells, where they regulate metastatic
      cell behaviours, including cellular movement and invasion. Treating cancer cells
      with the VGSC-inhibiting anticonvulsant phenytoin reduces cellular invasion and
      migration. Together, these suggest that VGSCs may be useful targets for
      inhibiting metastasis. The purpose of this study is to test the hypothesis that
      use of VGSC-inhibiting drugs will reduce metastasis, and therefore increase
      survival time in patients with cancer. METHODS AND ANALYSIS: A cohort study based
      on primary care data from the QResearch database will include patients with one
      of the three common tumours: breast, bowel and prostate. The primary outcome will
      be overall survival from the date of cancer diagnosis. Cox proportional hazards
      regression will be used to compare the survival of patients with cancer taking
      VGSC-inhibiting drugs (including anticonvulsants and class I antiarrhythmic
      agents) with patients with cancer not exposed to these drugs, adjusting for age
      and sex. Exposure to VGSC-inhibiting drugs will be defined as having at least one
      prescription for these drugs prior to cancer diagnosis. High and low exposure
      groups will be identified based on the length of use. A number of sensitivity and
      secondary analyses will be conducted. ETHICS AND DISSEMINATION: The protocol has
      been independently peer-reviewed and approved by the QResearch Scientific Board.
      The project has also been approved by the University of York Ethical Review
      Process. The results will be presented at international conferences and published
      in an open access peer-reviewed journal, in accordance with the Strengthening the
      Reporting of Observational Studies in Epidemiology (STROBE) criteria.

PMID- 25398680
TI  - Dosimetric Comparison of Craniospinal Irradiation Using Different Tomotherapy
      Techniques.
AB  - The objective of this study is to compare the new and conventional tomotherapy
      treatment techniques and to evaluate dosimetric differences between them. A
      dosimetric analysis was performed by comparing planning target volume (PTV)
      median dose, 95% of PTV dose coverage, Paddick conformity index (CI), homogeneity
      index (HI), whole-body integral dose, and OAR median doses. The beam on time
      (BOT) and the effect of different jaw sizes and pitch values was studied. The
      study results indicated that the PTV dose coverage for all the techniques was
      comparable. Treatment plans using dynamic jaw reduced OAR doses to structures
      located at the treatment field edge compared to fixed jaw plans. The HT-3DCRT
      plans resulted in higher OAR doses to kidney, liver, and lung compared to the
      other techniques, and TD-IMRT provided the best dose sparing to liver compared to
      other techniques. Whole-body integral dose differences were found to be
      insignificant among the techniques. BOT was found to be higher for fixed jaw
      treatment plan compared to dynamic jaw plan and comparable between all treatment
      techniques with 5-cm dynamic jaw. In studying effect of jaw size, better OAR
      sparing and HI were found for 2.5-cm jaw but at the expense of doubling of BOT as
      compared to 5-cm jaw. There was no significant improvement found in OAR sparing
      when the pitch value was increased. Increasing the pitch from 0.2 to 0.43, the CI
      was improved, HI improved only for 5-cm jaw size, and BOT decreased to
      approximately half of its original time. 

PMID- 25398681
TI  - Efficacy of the Dynamic Jaw Mode in Helical Tomotherapy With Static Ports for
      Breast Cancer.
AB  - The recently developed dynamic jaw technology of tomotherapy can reduce
      craniocaudal dose spread without much prolonging the treatment time. This study
      aimed to investigate the efficacy of the dynamic jaw mode for tomotherapy of
      breast cancer. Static tomotherapy plans of the whole breast and supraclavicular
      regional lymph nodes, and plans for the whole breast only were generated in 25
      patients with left-sided breast cancer. Plans with a field width of 2.5 or 5 cm
      with the dynamic or fixed jaw modes were made for each patient. The prescribed
      dose was 50 Gy in 25 fractions. In whole breast and supraclavicular nodal
      radiotherapy, dose distributions and homogeneity of the planning target volume
      (PTV) with the dynamic jaw mode were slightly inferior to those with the fixed
      jaw mode with a 5-cm field width (P < .05). However, lung low-dose volumes and
      mean doses of the larynx, thyroid, skin, and all the healthy tissues combined
      were smaller with the dynamic jaw mode than with the fixed jaw mode with a 5-cm
      field width (P < .001). In whole breast radiotherapy, mean doses of the skin and
      healthy tissues were lower with the dynamic jaw mode than with the fixed jaw mode
      with a 5-cm field width (P < .001) without significant differences in PTV dose
      distributions, homogeneity, and conformity. The dynamic jaw mode provided better
      sparing of organs at risks with minimal disturbance of dose-volume indices of
      PTV. Considering the treatment time, the 5-cm-field dynamic jaw mode is more
      efficient than the 2.5-cm fixed jaw mode. 

PMID- 25398683
TI  - Aberrant methylation of miR-34b is associated with long-term shiftwork: a
      potential mechanism for increased breast cancer susceptibility.
AB  - PURPOSE: Although the evidence linking exposure to light at night (LAN) and
      breast cancer risk continues to accumulate, the molecular mechanisms driving this
      association remain to be fully elucidated. We have previously suggested that long
      term exposure to LAN through shiftwork may result in dysregulated patterns of
      methylation genome-wide. In this study, we investigate the link between miR-34b,
      a miRNA suggested to be an important tumor suppressor, and shiftwork-related
      breast cancer. METHODS: Methylation states in the miR-34b promoter region were
      previously compared between 10 female long-term shiftworkers and 10 folate intake
      and age-matched female dayworkers participating in the Danish "Diet, Cancer and
      Health" prospective cohort study. In order to further explore the functional role
      of miR-34b in breast tumorigenesis, a genome-wide expression microarray was
      carried out in miR-34b-overexpressed MCF-7 breast cancer cells and the identified
      transcripts were further analyzed for network and functional interrelatedness
      using Ingenuity Pathway Analysis software. RESULTS: We observed a 49.1 % increase
      in miR-34b promoter methylation among shiftworkers at a CpG site in this region
      (p = 0.016). Transfection of the miR-34b mimic in an MCF-7 breast cancer cell
      line induced differential expression of 230 transcripts that are involved in the
      interferon-mediated antiviral response as well as apoptotic and antiproliferative
      gene networks. CONCLUSIONS: Together, our results suggest that long-term
      shiftwork may increase the risk of breast cancer via methylation-based
      suppression of miR-34b and a consequent reduction in immunomediated anti-tumor
      capacity and support our previous findings that LAN may induce epigenetic
      alteration of cancer-relevant microRNAs.

PMID- 25398682
TI  - Obesity and head and neck cancer risk and survival by human papillomavirus
      serology.
AB  - PURPOSE: Previous studies examining the association of body mass index (BMI) with
      risk of and survival from head and neck squamous cell carcinoma (HNSCC) have been
      inconsistent, although an inverse association has been noted for obesity and risk
      of HNSCC in several studies. Previous studies have not examined whether these
      associations differ by human papillomavirus (HPV) status. METHODS: We utilized
      the resources of a population-based case-control study of HNSCC from the greater
      Boston area (959 cases and 1,208 controls were eligible for this analysis).
      Anthropometric history was collected through personal interviews, and HPV status
      was assessed using serology. We analyzed the association between BMI (assessed 5
      years prior to disease incidence) and disease risk and survival using logistic
      regression and Cox proportional hazards regression, respectively. RESULTS: After
      adjusting for known risk factors, the association between obesity and overall
      risk of HNSCC was not significant (OR 0.79, 95 % CI 0.60-1.04). However, obesity
      (BMI >=30 kg/m(2)) was inversely associated with HNSCC risk among HPV
      seronegative cases (OR 0.48, 95 % CI 0.32-0.70), but not among HPV-seropositive
      cases (OR 0.91, 95 % CI 0.68-1.21). BMI was not associated with survival overall
      or by HPV status. However, being overweight (BMI 25-29.9 kg/m(2)) was associated
      with longer survival among HPV-seropositive smokers (HR 0.48, 95 % CI 0.31-0.74).
      CONCLUSIONS: Our findings are consistent with previous observations that obesity
      is inversely associated with the risk of HNSCC; however, this association appears
      to be confined to HPV-seronegative cases. Overall, obesity was not associated
      with HNSCC survival overall or by HPV status. IMPACT: Obesity is associated with
      risk of non-HPV HNSCC, but not HPV HNSCC.

PMID- 25398684
TI  - Efficacy of deltamethrin, diazinon, and ivermectin on Boophilus annulatus ticks
      (in vitro and in vivo study).
AB  - Tick infection is considered a cause of major concern as it is a vector for some
      disease transmission. The use of chemicals to control tick infection is
      increasing in farm systems. The efficacy of three chemicals was studied on the
      tick Boophilus annulatus. In vitro and in vivo studies were done. The active
      ticks were collected from naturally infected cattle for in vitro study. They were
      incubated with the three chemicals which are commercially used. An in vitro study
      recorded that the highest effect of the three chemicals was 100% at 3 h
      postexposure (p.e.) time for deltamethrin and 6 h for diazinon and ivermectin on
      the adult ticks. Egg batches were less affected. In vivo results showed more
      plain efficacy. The efficacy of deltamethrin was increased gradually until
      complete cessation of ticks showed within 3rd day posttreatment (d.p.t.), 100%
      efficacy. But the tick population begins to reappear gradually within 7 d.p.t.,
      while diazinon showed 100% efficacy at 7 d.p.t. and the ticks reappear again
      within 14 d.p.t. The most preferred results were obtained with ivermectin which
      showed 100% efficacy at 7 d.p.t., and the cattle was still free from infection
      until 21 d.p.t. only. Ticks begin to reappear within 28 d.p.t. in slight few
      numbers. This concluded that the powerful and safe chemical which is commercially
      used was ivermectin. Even so, it is used also as an anthelmintic drug.

PMID- 25398685
TI  - A novel CDPK1 inhibitor--a potential treatment for cryptosporidiosis in calves?
AB  - Cryptosporidium parvum is a zoonotic agent that infects humans and animals
      occasionally causing severe, watery diarrhoea. In immunocompetent hosts,
      cryptosporidiosis is self-limiting but can have a fatal outcome in
      immunocompromised individuals. Cryptosporidium is one of the most common causes
      of waterborne diseases (recreational water and drinking water) in humans, a
      leading cause of moderate to severe childhood diarrhoea, and a major agent of
      diarrhoea in calves leading to high economic losses and up to 10% lethality. So
      far, available treatment options are insufficient for both veterinary and human
      clinical disease cases. Here, we report for the first time that the novel bumped
      kinase inhibitor (BKI) 1294 targeting the calcium-dependent protein kinase 1
      (CDPK1) of Cryptosporidium is able to reduce the oocyst shedding of C. parvum by
      calves--its natural host--without obvious side effects.

PMID- 25398686
TI  - A nonparametric efficient evaluation of partial directed coherence.
AB  - Studying the flow of information between different areas of the brain can be
      performed using the so-called partial directed coherence (PDC). This measure is
      usually evaluated by first identifying a multivariate autoregressive model and
      then using Fourier transforms of the impulse responses identified and applying
      appropriate normalizations. Here, we present another way to evaluate PDCs in
      multivariate time series. The method proposed is nonparametric and utilizes a
      strong spectral factorization of the inverse of the spectral density matrix of a
      multivariate process. To perform the factorization, we have recourse to an
      algorithm developed by Davis and his collaborators. We present simulations as
      well as an application on a real data set (local field potentials in a sleeping
      mouse) to illustrate the methodology. A detailed comparison with the common
      approach in terms of complexity is made. For long autoregressive models, the
      proposed approach is of interest. 

PMID- 25398687
TI  - Stochastic resonance in visual sensitivity.
AB  - It is well known from psychophysical studies that stochastic resonance, in its
      simplest threshold paradigm, can be used as a tool to measure the detection
      sensitivity to fine details in noise contaminated stimuli. In the present
      manuscript, we report simulation studies conducted in the similar threshold
      paradigm of stochastic resonance. We have estimated the contrast sensitivity in
      detecting noisy sine-wave stimuli, with varying area and spatial frequency, as a
      function of noise strength. In all the cases, the measured sensitivity attained a
      peak at intermediate noise strength, which indicate the occurrence of stochastic
      resonance. The peak sensitivity exhibited a strong dependence on area and spatial
      frequency of the stimulus. We show that the peak contrast sensitivity varies with
      spatial frequency in a nonmonotonic fashion and the qualitative nature of the
      sensitivity variation is in good agreement with human contrast sensitivity
      function. We also demonstrate that the peak sensitivity first increases and then
      saturates with increasing area, and this result is in line with the results of
      psychophysical experiments. Additionally, we also show that critical area,
      denoting the saturation of contrast sensitivity, decreases with spatial frequency
      and the associated maximum contrast sensitivity varies with spatial frequency in
      a manner that is consistent with the results of psychophysical experiments. In
      all the studies, the sensitivities were elevated via a nonlinear filtering
      operation called stochastic resonance. Because of this nonlinear effect, it was
      not guaranteed that the sensitivities, estimated at each frequency, would be in
      agreement with the corresponding results of psychophysical experiments; on the
      contrary, close agreements were observed between our results and the findings of
      psychophysical investigations. These observations indicate the utility of
      stochastic resonance in human vision and suggest that this paradigm can be useful
      in psychophysical studies. 

PMID- 25398688
TI  - The phenomenology of suffering in medicine and bioethics.
AB  - This article develops a phenomenology of suffering with an emphasis on matters
      relevant to medical practice and bioethics. An attempt is made to explain how
      suffering can involve many different things-bodily pains, inability to carry out
      everyday actions, and failure to realize core life values-and yet be a distinct
      phenomenon. Proceeding from and expanding upon analyses found in the works of
      Eric Cassell and Elaine Scarry, suffering is found to be a potentially alienating
      mood overcoming the person and engaging her in a struggle to remain at home in
      the face of loss of meaning and purpose in life. Suffering involves painful
      experiences at different levels that are connected through the suffering-mood but
      are nevertheless distinguishable by being primarily about (1) my embodiment, (2)
      my engagements in the world together with others, and (3) my core life values.
      Suffering is in essence a feeling (a mood), but as such, it has implications for
      and involves the person's entire life: how she acts in the world, communicates
      with others, and understands and looks upon her priorities and goals in life.
      Suffering-moods are typically intense and painful in nature, but they may also
      display a rather subconscious quality in presenting things in the world and my
      life as a whole in an alienating way. In such situations, we are not focused
      directly upon the suffering-mood-as in the cases of pain and other bodily
      ailments-but rather, upon the things that the mood presents to us: not only our
      bodies, but also other things in the world that prevent us from having a good
      life and being the persons we want to be. Such suffering may in many cases be
      transformed or at least mitigated by a person's identifying and changing her core
      life values and in such a manner reinterpreting her life story to become an
      easier and more rewarding one to live under the present circumstances. 

PMID- 25398689
TI  - A dose-ranging study of the bronchodilator effects of abediterol (LAS100977), a
      long-acting beta2-adrenergic agonist, in asthma; a Phase II, randomized study.
AB  - BACKGROUND: Long-acting beta2-adrenergic agonists (LABAs) are recommended in
      combination with inhaled corticosteroids (ICSs) for asthma management. Abediterol
      is a novel, selective, potent, once-daily LABA in development for treatment of
      asthma and chronic obstructive pulmonary disease. This study aimed to determine
      abediterol doses with similar peak bronchodilatory effect to salbutamol 400 MUg,
      and duration of action compatible with once-daily dosing in patients with
      persistent, stable asthma. METHODS: This was a Phase II, randomized, double
      blind, double-dummy, crossover, placebo-controlled, dose-ranging study
      (ClinicalTrials.gov NCT01425801) in 62 patients with mild-to-moderate asthma who
      were also receiving an ICS. Patients received single doses of abediterol 0.313,
      0.625, 1.25, or 2.5 MUg, salbutamol 400 MUg, or placebo in the morning.
      Spirometry was performed up to 36 h post-dose; safety and tolerability were
      assessed throughout the study. The primary endpoint was change from baseline in
      peak forced expiratory volume in 1 s (FEV1). Additional endpoints included trough
      FEV1, normalized area under the FEV1 curve (FEV1 AUC) up to 24 h post-dose, and
      peak and trough forced vital capacity (FVC). RESULTS: Abediterol produced dose
      dependent improvements in peak FEV1 from baseline compared with placebo, from
      0.274 (95% CI 0.221, 0.327) to 0.405 L (95% CI 0.353, 0.458) for abediterol 0.313
      to 2.5 MUg, respectively (p < 0.0001 all doses). Abediterol 0.625, 1.25, and 2.5
      MUg had similar magnitude of peak FEV1 effect to salbutamol. Dose-dependent
      changes from baseline in trough FEV1 versus placebo were 0.219 (95% CI 0.136,
      0.302) to 0.400 L (95% CI 0.317, 0.483) for abediterol 0.313 to 2.5 MUg,
      respectively (p < 0.0001). All abediterol doses achieved significant improvements
      versus placebo in FEV1 AUC 0-6, 0-12, and 0-24 h, and peak and trough FVC (p <
      0.05). Less than 10% of patients experienced treatment-related adverse events for
      each dose of abediterol; most were mild to moderate in intensity and the most
      common were headache and nasopharyngitis. There were no clinically relevant
      changes in heart rate. CONCLUSIONS: Abediterol 0.625-2.5 MUg provided dose
      dependent, clinically and statistically significant bronchodilation versus
      placebo in patients with asthma, with a peak effect similar to salbutamol and
      duration of action compatible with once-daily dosing. All doses of abediterol
      were well tolerated.

PMID- 25398690
TI  - Effects of interleukin-18 promoter (C607A and G137C) gene polymorphisms and their
      association with oral squamous cell carcinoma (OSCC) in northern India.
AB  - Interleukin-18 (IL-18) is one of the immunomodulatory cytokines that plays an
      important role in cellular functions against tumor development and progression.
      IL-18 (-607) C/A and (-0137) G/C gene promoter polymorphisms and their haplotypes
      variants are associated with risk of various cancers. We evaluated a possible
      association of IL-18 (-607) C/A and (-137) G/C gene promoter polymorphisms in the
      susceptibility to oral squamous cell carcinoma (OSCC). A total number of 272
      patients with OSCC and 185 healthy volunteers were genotyped for the IL-18 (-607)
      C/A and (-137) G/C polymorphism. Polymorphism variants were examined by using
      tetra-primer amplification refractory mutation system (T-ARMS). Genotype
      frequencies were evaluated by chi-square test and odds ratio (OR) relative risk.
      IL-18 (-137) G/C gene polymorphism was significantly associated with the risk of
      OSCC as compared to healthy volunteers (genotype GG vs GC: OR 2.238; 95 % CI
      1.455-3.441; p = 0.0003 and allele G vs C: OR 1.984; 95 % CI 1.335-2.947; p =
      0.0007). The genotype and allele frequencies of the IL-18 promoter -607 C/A
      polymorphism in OSCC patients were not significantly different than that in
      healthy controls (p > 0.05). Our results suggest that IL-18 -137 G/C polymorphism
      is significantly associated with the progression of oral cancer but -607 C/A
      polymorphism is not associated with this. 

PMID- 25398691
TI  - Cu(II)-vitamin D interaction leads to free radical-mediated cellular DNA damage:
      a novel putative mechanism for its selective cytotoxic action against malignant
      cells.
AB  - Vitamin D (vit D) is a known anticancer molecule, and cancer cells are reported
      to have elevated levels of Cu(II) ions. In this study, we show that interaction
      of vit D and Cu(II) leads to the formation of hydroxyl free radicals, superoxide
      anion and hydrogen peroxide, which causes severe oxidative stress, selectively in
      malignant cells. We show that the production of these reactive oxygen species
      causes cellular DNA fragmentation which may cause cell death. A novel putative
      chemical mechanism explaining how vit D causes cell death by DNA damage,
      selectively in malignant cells, is proposed. 

PMID- 25398692
TI  - NSK-01105 inhibits proliferation and induces apoptosis of prostate cancer cells
      by blocking the Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways.
AB  - The purposes of this study are to investigate the antitumor activities of NSK
      01105, a novel sorafenib derivative, in in vitro and in vivo models, and explore
      the potential mechanisms. The effects of NSK-01105 on proliferation and apoptosis
      of prostate cancer cells were established by cytotoxicity assays, apoptosis
      analysis, flow cytometry analysis, and Western blot analysis. Two xenograft tumor
      models were used to verify the therapeutic effect of NSK-01105 in vivo. NSK-01105
      exhibited broad-spectrum antitumor activity, particularly in prostate cancer
      cells. Characterization of apoptosis morphology was observed, and the percentage
      of apoptosis-positive cells significantly increased after NSK-01105 treatment for
      24 h. Furthermore, a significant increase of the "sub-G1" population in LNCaP and
      PC-3 cells after NSK-01105 treatment was determined by cell cycle analysis. Tumor
      growth was significantly suppressed by once daily oral 30 mg/kg dose of NSK-01105
      with the inhibition rates of 63.82% in LNCaP models and 64.29% in PC-3 models,
      respectively. The activation of Raf-1 kinase and epidermal growth factor receptor
      was downregulated by NSK-01105 at 10 MUmol/L. Consequently, the dual inhibitions
      of Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways were observed by Western blot
      analysis. Collectively, our results suggest a role of NSK-01105 in treatment for
      human prostate tumors by inhibiting cell proliferation and inducing apoptosis.
      NSK-01105 appears to be a promising orally active anticancer drug and deserves
      further investigation.

PMID- 25398693
TI  - Knockdown of PSF1 expression inhibits cell proliferation in lung cancer cells in
      vitro.
AB  - Partner of sld five 1 (PSF1) is a member of the heterotetrameric complex termed
      GINS. Previous studies have shown that PSF1 is unregulated in several cancer and
      associated with tumor malignant characters. However, the effects of PSF1 in lung
      cancer are still unclear. The goal of this study was to investigate the effects
      of PSF1 on the proliferation capacities of lung cancer. To start with, expression
      of PSF1 in 22 human lung cancer samples and adjacent non-tumor samples were
      detected by real-time RT-PCR and Western blotting. Our results showed that PSF1
      was overexpressed in lung cancer samples compared to adjacent non-tumor samples.
      To achieve better insights of PSF1 functions in lung cancer cells, we used PSF1
      specific small interfering RNA (siRNA) successfully inhibit the expression of
      PSF1 in messenger RNA (mRNA) and protein levels. In addition, we used lung cancer
      cell lines with different p53 gene background (p53 null and p53 wild-type). The
      results showed that knockdown of PSF1 inhibited cell proliferation and caused
      cell cycle arrest of lung cancer cells in a p53-independent manner. Our data
      indicated that PSF1 is functionally involved in lung cancer cell proliferation
      and is a potential target for lung cancer therapy. 

PMID- 25398694
TI  - Metabolic components and recurrence in early-stage cervical cancer.
AB  - Epidemiological evidence suggests that the metabolic syndrome (MetS) is
      associated with increased risk of cervical cancer. However, research on the
      impact of MetS on prognosis in cervical cancer is lacking. This study
      investigated the association between MetS and recurrence-free survival (RFS) in
      patients with early-stage cervical cancer. This is a retrospective study of
      patients diagnosed with the International Federation of Gynecology and Obstetrics
      (FIGO) stage I-II cervical cancer in three tertiary hospitals during 2006-2009.
      Cox proportional hazards model was used to estimate the association between MetS
      or MetS components and RFS. We were able to evaluate MetS status in 84 patients
      out of 127. Forty patients had MetS. RFS was not significantly different
      according to MetS status; however, there was no further event of recurrence in
      non-MetS group after 2 years from primary surgical treatment.
      Hypertriglyceridemia (HR 3.67, 95% CI 1.18-11.43) and impaired fasting glucose
      (HR 4.30, 95% CI 1.23-15.03) were independent risk factors for shorter RFS, after
      adjustment for age, lymph node involvement, tumor involvement of resection
      margin, parametrial invasion, FIGO stage at diagnosis, and adjuvant treatment.
      Hypertriglyceridemia and impaired fasting glucose were associated with higher
      risk of recurrence in patients with early-stage cervical cancer. Prospective
      validation in large populations and further studies on the impact of MetS
      treatment in patients with cervical cancer are warranted.

PMID- 25398695
TI  - Inhibition of Excessive Monoamine Oxidase A/B Activity Protects Against Stress
      induced Neuronal Death in Huntington Disease.
AB  - Monoamine oxidases (MAO) are important components of the homeostatic machinery
      that maintains the levels of monoamine neurotransmitters, including dopamine, in
      balance. Given the imbalance in dopamine levels observed in Huntington disease
      (HD), the aim of this study was to examine MAO activity in a mouse striatal cell
      model of HD and in human neural cells differentiated from control and HD patient
      derived induced pluripotent stem cell (hiPSC) lines. We show that mouse striatal
      neural cells expressing mutant huntingtin (HTT) exhibit increased MAO expression
      and activity. We demonstrate using luciferase promoter assays that the increased
      MAO expression reflects enhanced epigenetic activation in striatal neural cells
      expressing mutant HTT. Using cellular stress paradigms, we further demonstrate
      that the increase in MAO activity in mutant striatal neural cells is accompanied
      by enhanced susceptibility to oxidative stress and impaired viability. Treatment
      of mutant striatal neural cells with MAO inhibitors ameliorated oxidative stress
      and improved cellular viability. Finally, we demonstrate that human HD neural
      cells exhibit increased MAO-A and MAO-B expression and activity. Altogether, this
      study demonstrates abnormal MAO expression and activity and suggests a potential
      use for MAO inhibitors in HD. 

PMID- 25398697
TI  - Plasma pharmacokinetics and tissue and brain distribution of cisplatin in musk
      shrews.
AB  - PURPOSE: Cisplatin induces nausea and emesis, even with antiemetic supportive
      care. To assess platinum exposure, which could activate nausea and emesis, we
      quantitated platinum in the brain and various organs, and hindbrain and spinal
      cord substance P, a key neuropeptide for the neuronal signaling of nausea and
      emesis. METHODS: Musk shrews, a model species for nausea and emesis research,
      were dosed intraperitoneally with 20 mg/kg cisplatin and euthanized at up to 72 h
      after injection. Concentrations of platinum were quantitated in plasma
      ultrafiltrate, plasma, lung, kidney, combined forebrain and midbrain, hindbrain,
      and spinal cord by flameless atomic absorption spectrometry. Hindbrains and
      spinal cords were analyzed for substance P by immunohistochemistry after
      injection of 20 or 30 mg/kg. RESULTS: Plasma ultrafilterable platinum
      concentrations decreased rapidly till 60 min after dosing and then more slowly by
      24 h. The concentrations of total platinum in both the fore- and midbrain and the
      hindbrain were similar at all time points and were at least 20-fold lower than
      plasma total platinum concentrations. There were no significant changes in
      substance P immunoreactivity after cisplatin dosing. Histology revealed damage to
      the renal cortex by 72 h after injection of cisplatin. CONCLUSIONS: This is the
      first study to examine platinum concentrations in musk shrews after
      administration of cisplatin and delineate substance P immunohistochemical
      staining in the hindbrain and spinal cord of this species. The platinum
      concentrations detected in the brain could potentially contribute to the
      neurological side effects of cisplatin, such as nausea and emesis.

PMID- 25398698
TI  - Docetaxel, gemcitabine and bevacizumab as salvage chemotherapy for HER-2-negative
      metastatic breast cancer.
AB  - PURPOSE: To evaluate the activity and safety of the docetaxel, gemcitabine and
      bevacizumab combination, administered biweekly, in pretreated patients with HER-2
      negative metastatic breast cancer (MBC). PATIENTS AND METHODS: Women with HER-2
      negative MBC, and disease progression after at least one prior line of
      chemotherapy, were treated with docetaxel 50 mg/m2, gemcitabine 1,500 mg/m2 and
      bevacizumab 10 mg/kg every 2 weeks. Bevacizumab was continued until disease
      progression. RESULTS: Forty-eight patients have been enrolled. Their median age
      was 61 years, 95.8 % had a performance status 0-1, 83.3 % had hormone receptor
      positive disease, and 47.9 % had received one prior line of chemotherapy. All
      patients were evaluable for toxicity and 45 for response. Partial response was
      achieved in 20 patients [PR = 44.4 %, 95 % confidence interval (CI) 29.9-59 %]
      and disease stabilization in 15 (33.3 %). The median progression-free survival
      was 7.1 months (95 % CI 4.7-9.5 months) and the median overall survival 21.1
      months (95 % CI 10.3-31.9 months). Grade 3-4 neutropenia occurred in 19 patients
      (39.6 %) and febrile neutropenia in 2 (4.2 %). Most common grade 2-3 non
      hematologic adverse events included nausea (10.4 %), diarrhea (10.5 %),
      neurotoxicity (12.5 %) and fatigue (31.3 %), whereas grade 2 hemorrhage and
      hypertension occurred in 6.3 and 10.4 %, respectively. There were no grade 4 non
      hematologic toxicities or toxic deaths. CONCLUSION: The combination of docetaxel,
      gemcitabine and bevacizumab has promising activity and manageable toxicity as
      salvage chemotherapy for HER-2-negative MBC patients.

PMID- 25398699
TI  - Ectopic perianal varix in a patient with portal hypertension: a rare cause of
      hematochezia.

PMID- 25398700
TI  - A migrant study of pubertal timing and tempo in British-Bangladeshi girls at
      varying risk for breast cancer.
AB  - INTRODUCTION: Earlier menarche is related to subsequent breast cancer risk, yet
      international differences in the age and tempo of other pubertal milestones and
      their relationships with body mass index (BMI) are not firmly established in
      populations at differing risk for breast cancer. We compared age and tempo of
      adrenarche, thelarche, pubarche, and menarche in a migrant study of Bangladeshi
      girls to the United Kingdom (UK) and assessed whether differences by migration
      were explained by differences in BMI. METHODS: Included were groups of
      Bangladeshi (n =168), British-Bangladeshi (n =174) and white British (n =54)
      girls, aged 5 to 16 years. Interviewer-administered questionnaires obtained
      pubertal staging; height and weight were measured. Salivary
      dehydroepiandrosterone-sulfate concentrations >400 pg/ml defined adrenarche.
      Median ages of pubertal milestones and hazard ratios (HR) with 95% confidence
      intervals (CI) were estimated from Weibull survival models. RESULTS: In all three
      groups, adrenarche occurred earliest, followed by thelarche, pubarche, and
      finally menarche. Neither median age at adrenarche (Bangladeshi = 7.2, British
      Bangladeshi = 7.4, white British = 7.1; P-trend = 0.70) nor at menarche
      (Bangladeshi = 12.5, British-Bangladeshi = 12.1, white British = 12.6; P-trend =
      0.70) differed across groups. In contrast, median age at thelarche (Bangladeshi =
      10.7, British-Bangladeshi = 9.6, white British = 8.7; P-trend <0.01) occurred
      earlier among girls living in the UK. Compared with Bangladeshi girls, HRs (95%
      CI) for earlier thelarche were 1.6 (1.1 to 2.4) for British-Bangladeshi girls and
      2.6 (1.5 to 4.4) for white British girls (P-trend <0.01), but were attenuated
      after adjustment for BMI (British-Bangladeshi = 1.1 (0.7 to 1.8), white British =
      1.7(1.0 to 3.1); P-trend =0.20). CONCLUSIONS: Thelarche occurred earlier, but
      puberty progressed slower with increasing exposure to the UK environment;
      differences were partially explained by greater BMI. The growth environment might
      account for much of the ethnic differences in pubertal development observed
      across and within countries.

PMID- 25398702
TI  - Cardiovascular manifestations of HIV infection in children.
AB  - BACKGROUND: HIV infection in children is now considered as a chronic condition,
      in which various non-infectious complications may occur, including those
      affecting the developing cardiovascular system. As children are expected to
      survive well into adulthood, understanding childhood as well as potential future
      cardiovascular complications is of major importance. METHODS AND RESULTS: We
      reviewed published literature on childhood cardiac manifestations and longer term
      effects of pediatric HIV infection on the cardiovascular system. Evidence gaps
      that should be prioritized in research are highlighted. Through poorly understood
      mechanisms, HIV infection may cause various cardiac complications already
      manifesting in childhood, such as structural and functional myocardial
      derangements, pulmonary hypertension, pericardial effusion and possibly
      endocarditis. Evidence indicates that HIV infection in children also has
      unfavorable effects on the vasculature and cardiovascular biomarkers, such as
      increased intima-media thickness and decreased flow-mediated dilation, a marker
      of endothelial function. However, studies are small and predominantly include
      antiretroviral therapy-treated children, so that it is difficult to differentiate
      between effects of HIV infection per se and antiretroviral therapy treatment,
      reported in adults to have cardiovascular side effects. CONCLUSIONS: HIV
      infection in children may greatly impact the cardiovascular system, including
      effects on the heart, which tend to manifest early in childhood, and on the
      vasculature. The underlying mechanisms, essential for targeted prevention, are
      poorly understood. Current evidence largely stems from research in adults.
      However, as modes of infection, immune maturity, growth and development, and
      treatment are markedly different in children, specific pediatric research,
      accounting for the complex interplay of normal growth and development, HIV
      infection and treatment, is clearly warranted.

PMID- 25398701
TI  - Medication-related fall incidents in an older, ambulant population: the B-PROOF
      study.
AB  - BACKGROUND: Medication use is a potentially modifiable risk factor for falling;
      psychotropic and cardiovascular drugs have been indicated as main drug groups
      that increase fall risk. However, evidence is mainly based on studies that
      recorded falls retrospectively and/or did not determine medication use at the
      time of the fall. Therefore, we investigated the associations indicated in the
      literature between medication use and falls, using prospectively recorded falls
      and medication use determined at the time of the fall. METHODS: Data from the B
      PROOF (B-vitamins for the prevention of osteoporotic fractures) study were used,
      concerning community-dwelling elderly aged >=65 years. We included 2,407
      participants with pharmacy dispensing records. During the 2- to 3-year follow-up,
      participants recorded falls using a fall calendar. Cox proportional hazard models
      were applied, adjusting for potential confounders including age, sex, health
      status variables and concomitant medication use. RESULTS: During follow-up, 1,147
      participants experienced at least one fall. Users of anti-arrhythmic medication
      had an increased fall risk (hazard ratio [HR] 1.61; 95% confidence interval [CI]
      1.12-2.32) compared with non-users. Similarly, non-selective beta-blocker use was
      associated with an increased fall risk (HR 1.41 [95% CI 1.12-1.78]), while statin
      use was associated with a lower risk (HR 0.81 [95% CI 0.71-0.94]). Benzodiazepine
      use (HR 1.32 [95% CI 1.02-1.71]), and antidepressant use (HR 1.40 [95% CI 1.07
      1.82]) were associated with an increased fall risk. Use of other cardiovascular
      and psychotropic medication was not associated with fall risk. CONCLUSION: Our
      results strengthen the evidence for an increased fall risk in community-dwelling
      elderly during the use of anti-arrhythmics, non-selective beta-blockers,
      benzodiazepines, and antidepressant medication. Clinicians should prescribe these
      drugs cautiously and if possible choose safer alternatives for older patients.

PMID- 25398703
TI  - Exercise-based cardiac rehabilitation in patients with heart failure: a meta
      analysis of randomised controlled trials between 1999 and 2013.
AB  - BACKGROUND: Guidelines recommend exercise-based cardiac rehabilitation (EBCR) for
      patients with heart failure (HF). However, established research has not
      investigated the longer-term outcomes including mortality and hospitalisation in
      light of the contemporary management of HF. METHODS: This was a systematic review
      including a meta-analysis of EBCR on all-cause mortality, hospital admission, and
      standardised exercise capacity using four separate exercise tests in patients
      with heart failure over a minimum follow-up of six months from January 1999
      January 2013. Electronic searches were performed in the databases: Medline,
      CENTRAL, EMBASE, CINAHL, and PsycINFO constrained to randomised controlled trials
      (RCTs). RESULTS: A total of 46 separate RCTs qualified for the meta-analysis,
      which employed conventional methods for binary and continuous data. The relative
      risk (RR) ratio for hospital admission (12 studies) was significantly reduced (RR
      ratio 0.65; 95% confidence interval (CI) 0.50-0.84; p = 0.001), but mortality (21
      studies) was not (RR ratio 0.88; 95% CI 0.77-1.02; p = 0.08). The standardised
      exercise capacity (26 studies) showed a standardised mean difference (SMD) in
      favour of the exercise group as compared with the controls (SMD 0.98, 95% CI 0.59
      1.37; p < 0.001). Women and elderly people were less frequently enrolled in the
      RCTs independent of the outcomes. Heterogeneity was moderate to high in the
      analysis of hospital admission and the standardised exercise capacity
      demonstrated through skewedness in their funnel plots. CONCLUSIONS: EBCR in
      patients with HF is associated with significant improvements in exercise capacity
      and hospital admission over a minimum of six months follow-up, but not in all
      cause mortality.

PMID- 25398704
TI  - Safety and health status following early discharge in patients with acute
      myocardial infarction treated with primary PCI: a randomized trial.
AB  - BACKGROUND: Early discharge after uncomplicated primary percutaneous coronary
      intervention (PPCI) is common but the evidence supporting this practice is
      lacking. We therefore performed a randomized, prospective trial comparing
      outcomes in low risk PPCI randomized to early discharge or usual care. DESIGN AND
      METHODS: Over a two years period, all surviving PPCI patients at a single
      teaching hospital were considered eligible if the Zwolle risk score <=3. They
      were randomized to either discharge <=3 days or usual care. All included patients
      had routine medical treatment, counselling and follow-up. Health status and all
      readmissions up to 30 days follow-up were tracked. RESULTS: Of 425 consecutive
      PPCI patients, 215 (50.6%) were randomized to either early discharge (n = 108) or
      usual routine discharge (n = 107). The mean index length of stay (LOS) plus the
      30 days readmissions length of stay in the early discharge group was lower than
      in the usual discharge group: 2.7 +/- 0.5 days vs 3.0 +/- 0.7 days (p = 0.001).
      During follow-up there were no deaths, and similar readmission rate (4 (3.7%) vs
      3 (2.8%), p = 0.69 in the early vs usual discharge group respectively). There was
      no difference in the 30 days health status measurements. The excluded high-risk
      group (n = 210) had longer index LOS (total sum 1314 vs 501 days, p = 0.001), and
      a trend towards more readmissions (10 (4.8%) vs 7 (3.3%) (p = 0.19)). CONCLUSION:
      It is feasible and safe to discharge low-risk PPCI patients within three days.

PMID- 25398706
TI  - Editor's note February 2015.

PMID- 25398705
TI  - Diadenosine tetraphosphate contributes to carbachol-induced tear secretion.
AB  - The purpose of this study is to investigate if the cholinergic stimulation by
      carbachol on tear secretion is a direct process or if it is also mediated by
      purinergic mechanisms. Experiments were performed in New Zealand male rabbits.
      The amount of tear secretion was measured with Schirmer's test and then analyzed
      by a HPLC protocol in order to study the nucleotide levels. Animal eyes were
      instilled with carbachol (a cholinergic agonist), pirenzepine, gallamine and 4
      DAMP (muscarinic antagonists), PPADS, suramin and reactive blue 2 (purinergic
      antagonists), and a P2Y2 receptor small interfering RNA (siRNA). Tear secretion
      increased with the instillation of carbachol, approximately 84 % over control
      values 20 min after the instillation and so did Ap4A and ATP release. When we
      applied carbachol in the presence of muscarinic antagonists, tear volume only
      increased to 4 % with atropine, 12 % in the case of pirenzepine, 3 % with
      gallamine, and 8 % with 4-DAMP. In the presence of carbachol and purinergic
      antagonists, tear secretion was increased to 12 % (all values compared to basal
      tear secretion). By analyzing tear secretion induced with carbachol in presence
      of a P2Y2 receptor siRNA, we found that tear secretion was diminished to 60 %.
      The inhibition of tear secretion in the presence of carbachol and purinergic
      antagonists or P2Y2 siRNA occurred with no apparent change in the tear amount of
      Ap4A. These experiments demonstrated the participation of Ap4A in lacrimal
      secretion process.

PMID- 25398707
TI  - Force steadiness during a co-contraction task can be improved with practice, but
      only by young adults and not by middle-aged or old adults.
AB  - NEW FINDINGS: What is the central question of this study? Does the capacity to
      modulate afferent input to spinal motor neurons during steady submaximal
      contractions change with advancing age? What is the main finding and its
      importance? After practising a co-contraction task involving lower leg muscles,
      young subjects improved force steadiness by reducing the amount of Ia presynaptic
      inhibition as indexed by D1 inhibition. Middle-aged and old adults both found the
      task challenging, and force steadiness even worsened for old adults after
      practising the co-contraction task. Despite similar muscle strength for young and
      middle-aged adults, the capacity to modulate a spinal reflex pathway was reduced
      in middle-aged adults. This study compared the changes in steadiness and the
      modulation of presynaptic inhibition of soleus Ia afferents in young, middle-aged
      and old adults before and after a single session of practising a task that
      involved concurrent contraction of dorsiflexor and plantarflexor muscles. The
      hypothesis was that young subjects would be able to improve steadiness with
      practice by modulating Ia afferent feedback as indicated by changes in a measure
      of presynaptic inhibition (D1 inhibition), but that middle-aged and older
      subjects would exhibit a lesser ability to augment steadiness. There were no
      differences in steadiness between groups during an initial co-contraction trial
      (P = 0.713). Maximal voluntary contraction force for the plantarflexors was not
      significantly different between young and middle-aged subjects (P > 0.05), but it
      was significantly less in old subjects (P < 0.05). The main finding of the study
      was that young adults were able to improve steadiness by ~19% (P < 0.001) during
      a co-contraction task after 50 min of practice, whereas there was no change for
      the middle-aged adults, and old adults became less steady by ~15% (P < 0.05). The
      improvement in steadiness by young adults was accompanied by a significant
      reduction in the amount of Ia presynaptic inhibition as indexed by D1 inhibition
      (P < 0.01). Conversely, neither of the other two groups exhibited any change in
      D1 inhibition after practising the co-contraction task. In contrast to young
      subjects, middle-aged and old adults found the co-contraction task challenging
      and were not able to improve steadiness after practising the low-force isometric
      contraction.

PMID- 25398709
TI  - Regulation of exercise-induced lipid metabolism in skeletal muscle.
AB  - Exercise increases the utilization of lipids in muscle. The sources of lipids are
      long-chain fatty acids taken up from the plasma and fatty acids released from
      stores of intramuscular triacylglycerol by the action of intramuscular lipases.
      In the present review, we focus on the role of fatty acid binding proteins,
      particularly fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in
      the exercise- and contraction-induced increase in uptake of long-chain fatty
      acids in muscle. The FAT/CD36 translocates from intracellular depots to the
      surface membrane upon initiation of exercise/muscle contractions. This occurs
      independently of AMP-activated protein kinase, and data suggest that Ca(2+)
      related signalling is responsible. The FAT/CD36 has an important role; long-chain
      fatty acid uptake is markedly decreased in FAT/CD36 knockout mice during
      contractions/exercise compared with wild-type control mice. In skeletal muscle,
      98% of the lipase activity is accounted for by adipose triglyceride lipase and
      hormone-sensitive lipase. Give that inhibition or knockout of hormone-sensitive
      lipase does not impair lipolysis in muscle during contraction, the data point to
      an important role of adipose triglyceride lipase in regulation of muscle
      lipolysis. Although the molecular regulation of the lipases in muscle is not
      understood, it is speculated that intramuscular lipolysis may be regulated in
      part by the availability of the plasma concentration of long-chain fatty acids. 

PMID- 25398710
TI  - The effects of sex and neonatal stress on pituitary adenylate cyclase-activating
      peptide expression.
AB  - NEW FINDINGS: What is the central question of this study? Does sex or neonatal
      stress affect the expression of pituitary adenylate cyclase-activating peptide or
      its receptors? What is the main finding and its importance? Neonatal-maternal
      separation stress has little long-lasting effect on the expression of pituitary
      adenylate cyclase-activating peptide or its receptors, but sex differences exist
      in these genes between males and females at baseline. Sex differences in classic
      stress hormones have been studied in depth, but pituitary adenylate cyclase
      activating peptide (PACAP), recently identified as playing a critical role in the
      stress axes, has not. Here we studied whether baseline levels of PACAP differ
      between sexes in various stress-related tissues and whether neonatal-maternal
      separation stress has a sex-dependent effect on PACAP gene expression in stress
      pathways. Using quantitative RT-PCR, we found sex differences in PACAP and PACAP
      receptor gene expression in several respiratory and/or stress-related tissues,
      while neonatal-maternal separation stress did little to affect PACAP signalling
      in adult animals. We propose that sex differences in PACAP expression are likely
      to contribute to differences between males and females in responses to stress.

PMID- 25398712
TI  - Heart rate complexity in sinoaortic-denervated mice.
AB  - NEW FINDINGS: What is the central question of this study? New measurements for
      cardiovascular complexity, such as detrended fluctuation analysis (DFA) and
      multiscale entropy (MSE), have been shown to predict cardiovascular outcomes.
      Given that cardiovascular diseases are accompanied by autonomic imbalance and
      decreased baroreflex sensitivity, the central question is: do baroreceptors
      contribute to cardiovascular complexity? What is the main finding and its
      importance? Sinoaortic denervation altered both DFA scaling exponents and MSE,
      indicating that both short- and long-term mechanisms of complexity are altered in
      sinoaortic denervated mice, resulting in a loss of physiological complexity.
      These results suggest that the baroreflex is a key element in the complex
      structures involved in heart rate variability regulation. Recently, heart rate
      (HR) oscillations have been recognized as complex behaviours derived from non
      linear processes. Physiological complexity theory is based on the idea that
      healthy systems present high complexity, i.e. non-linear, fractal variability at
      multiple scales, with long-range correlations. The loss of complexity in heart
      rate variability (HRV) has been shown to predict adverse cardiovascular outcomes.
      Based on the idea that most cardiovascular diseases are accompanied by autonomic
      imbalance and a decrease in baroreflex sensitivity, we hypothesize that the
      baroreflex plays an important role in complex cardiovascular behaviour. Mice that
      had been subjected to sinoaortic denervation (SAD) were implanted with catheters
      in the femoral artery and jugular vein 5 days prior to the experiment. After
      recording the baseline arterial pressure (AP), pulse interval time series were
      generated from the intervals between consecutive values of diastolic pressure.
      The complexity of the HRV was determined using detrended fluctuation analysis and
      multiscale entropy. The detrended fluctuation analysis alpha1 scaling exponent (a
      short-term index) was remarkably decreased in the SAD mice (0.79 +/- 0.06 versus
      1.13 +/- 0.04 for the control mice), whereas SAD slightly increased the alpha2
      scaling exponent (a long-term index; 1.12 +/- 0.03 versus 1.04 +/- 0.02 for
      control mice). In the SAD mice, the total multiscale entropy was decreased (13.2
      +/- 1.3) compared with the control mice (18.9 +/- 1.4). In conclusion, fractal
      and regularity structures of HRV are altered in SAD mice, affecting both short-
      and long-term mechanisms of complexity, suggesting that the baroreceptors play a
      considerable role in the complex structure of HRV.

PMID- 25398713
TI  - Mechanisms of carotid body chemoreflex dysfunction during heart failure.
AB  - NEW FINDINGS: What is the topic of this review? Carotid body chemoreceptor
      activity is tonically elevated in heart failure and contributes to morbidity due
      to the reflex activation of sympathetic nerve activity and destabilization of
      breathing. The potential causes for the enhanced chemoreceptor activation in
      heart failure are discussed. What advances does it highlight? The role of a
      chronic reduction in blood flow to the carotid body due to cardiac failure and
      its impact on signalling pathways in the carotid body is discussed. Recent
      advances have attracted interest in the potential for carotid body (CB) ablation
      or desensitization as an effective strategy for clinical treatment and management
      of cardiorespiratory diseases, including hypertension, heart failure, diabetes
      mellitus, metabolic syndrome and renal failure. These disease states have in
      common sympathetic overactivity, which plays an important role in the development
      and progression of the disease and is often associated with breathing
      dysregulation, which in turn is likely to mediate or aggravate the autonomic
      imbalance. Evidence from both chronic heart failure (CHF) patients and animal
      models indicates that the CB chemoreflex is enhanced in CHF and contributes to
      the tonic elevation in sympathetic activity and the development of periodic
      breathing associated with the disease. Although this maladaptive change is likely
      to derive from altered function at all levels of the reflex arc, a tonic increase
      in afferent activity from CB glomus cells is likely to be a main driving force.
      This report focuses on our understanding of mechanisms that alter CB function in
      CHF and their potential translational impact on treatment of CHF.

PMID- 25398714
TI  - Selective carotid body ablation in experimental heart failure: a new therapeutic
      tool to improve cardiorespiratory control.
AB  - NEW FINDINGS: What is the topic of this review? This review summarizes the
      physiological role played by the carotid body in the autonomic dysregulation and
      breathing disturbances during the progression of chronic heart failure and the
      therapeutic potential of carotid body ablation to control cardiorespiratory
      imbalance and improve survival in heart failure. What advances does it highlight?
      Carotid body ablation markedly improves breathing stability and normalizes
      autonomic function in chronic heart failure. More importantly, if carotid body
      ablation is performed early during the progression of the disease it
      significantly improves animal survival. Chronic heart failure (CHF) is a leading
      medical problem worldwide. Common hallmarks of CHF include autonomic imbalance
      and breathing disorders, both of which are closely related to the progression of
      the disease and strongly predict mortality in CHF patients. The role played by
      the carotid body (CB) chemoreceptors in the progression of CHF has received
      attention because enhanced carotid chemoreflex drive is thought to contribute to
      autonomic dysfunction, abnormal breathing patterns and increased mortality in
      CHF. Therefore, therapeutic tools intended to normalize CB-mediated chemoreflex
      drive could have the potential to improve quality of life and decrease mortality
      of CHF patients. In experimental CHF, an enhancement of the CB chemoreflex drive,
      elevated sympathetic outflow, increased resting breathing variability, increased
      incidence of apnoea and desensitization of the baroreflex have been shown.
      Notably, selective elimination of the CB reduced central presympathetic neuronal
      activation, normalized sympathetic outflow and baroreflex sensitivity and
      stabilized breathing function in CHF. More remarkably, CB ablation has been shown
      to be a valuable therapeutic tool that significantly reduced aberrant cardiac
      remodelling, improved left ventriclular ejection fraction and reduced cardiac
      arrhythmogenesis. Most importantly, animals with CHF that underwent CB ablation
      showed a marked improvement in survival rate. Interestingly, a case report from a
      heart failure patient in whom unilateral CB ablation was performed showed
      promising results, with significant improvement in autonomic balance and
      breathing variability. Together, the CHF data from experimental animals as well
      as humans unveil a major role for the CB chemoreceptors in the progression of
      heart failure and support the notion that CB ablation could represent a novel
      therapeutic strategy to reduce cardiorespiratory dysfunction and improve survival
      during heart failure.

PMID- 25398715
TI  - Chemoreflex physiology and implications for sleep apnoea: insights from studies
      in humans.
AB  - NEW FINDINGS: What is the topic of this review? This review summarizes
      chemoreflex physiology in health and disease, with specific focus on chemoreflex
      mediated pathophysiology in obstructive and central sleep apnoea. What advances
      does it highlight? Chemoreflex mechanisms are thought to contribute significantly
      to the pathophysiology and adverse outcomes seen in sleep apnoea. Clinical
      implications of altered chemoreflex function in sleep apnoea from recent studies
      in humans, including cardiac arrhythmias, coronary artery disease,
      systolic/diastolic heart failure and sudden cardiac death are highlighted.
      Activation of the chemoreflex in response to hypoxaemia results in an increase in
      sympathetic neural outflow. This process is predominantly mediated by the
      peripheral chemoreceptors in the carotid bodies and is potentiated by the absence
      of the sympatho-inhibitory influence of ventilation during apnoea, as is seen in
      patients with sleep apnoea. In these patients, repetitive nocturnal hypoxaemia
      and apnoea elicit sympathetic activation, which may persist into wakefulness and
      is thought to contribute to the development of systemic hypertension and cardiac
      and vascular dysfunction. Chemoreflex activation could possibly lead to adverse
      cardiovascular outcomes, such as nocturnal myocardial infarction, systolic and/or
      diastolic heart failure, cardiac arrhythmias and sudden death in patients with
      sleep apnoea. This review summarizes chemoreflex physiology in health and
      disease, with specific focus on chemoreflex-mediated pathophysiology in
      obstructive and central sleep apnoea. Measurement of the chemoreflex response may
      serve as a potential avenue for individualized screening for cardiovascular
      disease. Whether modulation of this response in sleep apnoea may aid in the
      prevention and treatment of adverse cardiovascular consequences will require
      further study.

PMID- 25398716
TI  - Smooth muscle acid-sensing ion channel 1: pathophysiological implication in
      hypoxic pulmonary hypertension.
AB  - NEW FINDINGS: What is the topic of this review? An increase in pulmonary arterial
      smooth muscle cell intracellular Ca(2+) levels facilitates the enhanced
      vasoconstrictor and vascular remodeling responses associated with hypoxic
      pulmonary hypertension. Identifying the mechanisms of altered Ca(2+) homeostasis
      will advance our understanding of the pathogenesis of pulmonary hypertension and
      identify potential therapeutic targets. What advances does it highlight? Acid
      sensing ion channel 1 (ASIC1), present in pulmonary arterial smooth muscle cells,
      contributes to enhanced Ca(2+) entry and is an important constituent to the
      active vasoconstriction, vascular remodeling, and right ventricular hypertrophy
      associated with hypoxic pulmonary hypertension. Acid-sensing ion channels (ASICs)
      belong to the amiloride-sensitive, degenerin/epithelial sodium channel
      superfamily. Acid-sensing ion channels are voltage-independent, proton-gated
      cation channels, and their activity has been linked to a variety of physiological
      and pathological functions in the central and peripheral nervous system.
      Nonetheless, ASICs are expressed in a variety of tissues. In this review, we
      describe a novel role for ASIC1 in regulating pulmonary arterial smooth muscle
      cell (PASMC) Ca(2+) influx in both physiological and pathophysiological settings.
      Through a store-operated mechanism, ASIC1 contributes to pulmonary
      vasoconstriction elicited by various agonists and alveolar hypoxia. The ASIC1
      mediated Ca(2+) entry in PASMCs is a central component of the active
      vasoconstriction, vascular remodelling and right ventricular hypertrophy
      associated with the development of hypoxic pulmonary hypertension. Despite the
      requirement for ASIC1 to enhance Ca(2+) influx in the pulmonary hypertensive
      circulation, these responses are not dependent on an increase in PASMC ASIC1
      protein expression, suggesting that hypoxia promotes activation of ASIC1 through
      other regulatory mechanism(s). Here, I describe some of the correlations between
      hypoxia-induced changes in homeostasis of reactive oxygen species with that of
      ASIC1 function. Ultimately, a better understanding of the molecular mechanisms by
      which ASICs are regulated will help to elucidate their mechanism of action and
      identify potential therapeutics that specifically target ASICs.

PMID- 25398717
TI  - Vagus nerve contributes to metabolic syndrome in high-fat diet-fed young and
      adult rats.
AB  - NEW FINDINGS: What is the central question of this study? Different nerve
      contributes periods of life are known for their differential sensitivity to
      interventions, and increased parasympathetic activity affects the development and
      maintenance of obesity. Thus, we evaluated the involvement of the vagus nerve by
      performing a vagotomy in young or adult rats that were offered an obesogenic high
      fat diet. What is the main finding and its importance? Although the accumulation
      of adipose tissue decreased in both younger and older groups, the younger rats
      showed a greater response to the effects of vagotomy in general. In addition to
      the important role of the parasympathetic activity, we suggest that the vagus
      nerve contributes to the condition of obesity. Obesity has become a global
      problem, and this condition develops primarily because of an imbalance between
      energy intake and expenditure. The high complexity involved in the regulation of
      energy metabolism results from several factors besides endocrine factors. It has
      been suggested that obesity could be caused by an imbalance in the autonomous
      nervous system, which could lead to a condition of high parasympathetic activity
      in counterpart to low sympathetic tonus. High-fat (HF) diets have been used to
      induce obesity in experimental animals, and their use in animals leads to insulin
      resistance, hyperinsulinaemia and high parasympathetic activity, among other
      disorders. The aim of this work was to evaluate the effects of a vagotomy
      performed at the initiation of a HF diet at two different stages of life, weaning
      and adulthood. The vagotomy reduced parasympathetic activity (-32 and -51% in
      normal fat-fed rats and -43 and -55% in HF diet-fed rats; P < 0.05) and fat
      depots (-17 and -33%, only in HF diet-fed rats; P < 0.05). High-fat diet-fed rats
      exhibited fasting hyperinsulinaemia (fivefold higher in young rats and threefold
      higher in older rats; P < 0.05); however, vagotomy corrected it in younger rats
      only, and a similar effect was also observed during the glucose tolerance test.
      The insulin resistance exhibited by the HF diet-fed groups was not altered in the
      vagotomized rats. We suggest that the vagus nerve, in addition to the important
      role of parasympathetic activity, contributes to the condition of obesity, and
      that non-vagal pathways may be involved along with the imbalanced autonomic
      nervous system.

PMID- 25398718
TI  - Mechanisms linking connexin mutations to human diseases.
AB  - Ubiquitously expressed connexins are tetra-spanning transmembrane proteins that
      form intercellular gap junction channels or cell surface hemichannels. Connexins
      share similar topology but no sequence homology with mammalian pannexins and
      CALHM1 (calcium homeostasis modulator 1), which are also large-pore transmembrane
      channels. Of these three channel types, clinical evidence and gene sequence
      analysis to date have revealed that inherited human diseases are only associated
      with mutations in the connexin gene family. Connexin-linked diseases often
      present at birth or early in life and range from mild developmental abnormalities
      to severe organ failure such as hearing loss. Inherited connexin gene mutations
      can manifest as a disease by causing anomalies or defects in connexin
      oligomerization, folding, ability to pass quality control mechanisms or
      unexpected gain- or loss-of-function. This review provides examples of the way
      that various connexin gene mutations can cause disease via a wide range of
      molecular mechanisms. We also reflect on exciting strategies being explored in
      the connexin field and beyond with a view of translating their findings into
      potential connexin-disease therapeutics. 

PMID- 25398719
TI  - Roles of limbal microvascular net and limbal stroma in regulating maintenance of
      limbal epithelial stem cells.
AB  - Knowledge of the microenvironment (niche) of stem cells is helpful for stem-cell
      based regenerative medicine. In the eye, limbal epithelial stem cells (corneal
      epithelial stem cells) provide the self-renewal capacity of the corneal
      epithelium and are essential for maintaining corneal transparency and vision.
      Limbal epithelial stem cell deficiency results in significant visual
      deterioration. Successful treatment of this type of blinding disease requires
      studies of the limbal epithelial stem cells and their microenvironment. We
      investigate the function of the limbal microvascular net and the limbal stroma in
      the maintenace of the limbal epithelial stem cell niche in vivo and examine the
      regulation of limbal epithelial stem cell survival, proliferation and
      differentiation in vivo. We assess the temporal and spatial changes in the
      expression patterns of the following markers during a six-month follow-up of
      various rabbit limbal autograft transplantation models: vascular endothelial cell
      marker CD31, corneal epithelium differentiation marker K3, limbal epithelial stem
      cell-associated markers P63 and ABCG2 and proliferating cell nuclear marker Ki67.
      Our results suggest that limbal epithelial stem cells cannot maintain their
      stemness or proliferation without the support of the limbal microvascular net
      microenvironment. Thus, both the limbal microvascular net and the limbal stroma
      play important roles as components of the limbal epithelial stem cell niche
      maintaining limbal epithelial stem cell survival and proliferation and the
      avoidance of differentiation. The limbal stroma constitutes the structural basis
      of the limbal epithelial stem cell niche and the limbal microvascular net is a
      requirement for this niche. These new insights should aid the eventual
      construction of tissue-engineered cornea for corneal blind patients in the
      future. 

PMID- 25398720
TI  - Sepsis-induced lung inflammation is modulated by insulin.
AB  - BACKGROUND: We have previously shown that diabetic rats are more susceptible to
      sepsis, but that the Acute lung injury (ALI) secondary to sepsis is less intense
      than in non-diabetics. In the present study, we further investigated the ALI
      secondary to sepsis in diabetic rats and the effect of insulin treatment.
      METHODS: Diabetes was induced in male Wistar rats by alloxan and sepsis by cecal
      ligation and puncture surgery (CLP). Some diabetic rats were given neutral
      protamine Hagedorn (NPH) insulin (4 IU, s.c.) 2 h before CLP. Six h later, the
      lungs were examined for edema, cell infiltration and prostaglandin-E2 (PGE2)
      levels in the bronchoalveolar lavage (BAL). RESULTS: The results confirmed that
      leukocyte infiltration and edema were milder in diabetic rats with sepsis. After
      insulin treatment, the lung inflammation in diabetics increased to levels
      comparable to the non-diabetics. The BAL concentration of PGE2 was also lower in
      diabetics with sepsis, and increased after insulin treatment. Sepsis was followed
      by early fibroblast activation in the lung parenchyma, evaluated by increased
      transforming growth factor (TGF)-beta and smooth muscle actin (alpha-SMA)
      expression, as well as an elevated number of cells with myofibroblasts
      morphology. These events were significantly lower in diabetic rats and increased
      after insulin treatment. CONCLUSION: The results show that insulin modulates the
      early phase of inflammation and myofibroblast differentiation in diabetic rats.

PMID- 25398721
TI  - Gestational trophoblastic neoplasia: treatment outcomes from a single
      institutional experience.
AB  - PURPOSE: To report the outcomes of gestational trophoblastic neoplasia (GTN) at a
      single institution and to determine the factors affecting response to
      chemotherapy and survival. METHODS/PATIENTS: From 1979-2010, we retrospectively
      reviewed the data of 221 patients treated at our center. GTN Patients were
      assigned to low-risk (score <=6) or high-risk (score >=7) based on the WHO risk
      factor scoring system. Overall survival (OS) probabilities were estimated using
      Kaplan-Meier method. Logistic regression was applied to study the impact of
      different factors on the response to initial therapy. RESULTS: Patients' OS rate
      was 97 %. Median age at diagnosis was 37 year. 131 (59 %) patients had low-risk
      and 88 (40 %) cases had high-risk GTN. Complete remission rates to initial
      chemotherapy in low-risk group were 53 % and 87 % for single-agent methotrexate
      or dactinomycin, respectively. In high-risk group, 94 % achieved complete
      remission to initial chemotherapy with etoposide, methotrexate, dactinomycin,
      cyclophosphamide, and vincristine (EMA-CO). Etoposide, cisplatin, and
      dactinomycin as primary therapy in high-risk patients was successful in 70 %,
      while bleomycin, etoposide, and cisplatin (BEP) was successful in 53 % of cases.
      Salvage chemotherapy, surgical intervention or radiation therapy resulted in
      overall complete remission of 90 % in low-risk and 73 % in high-risk groups.
      Factors associated with resistance to initial chemotherapy were advanced-stage
      III/IV (p = 0.005), metastatic site other than lung or vagina (p = 0.005) and
      high-risk prognostic score (p = 0.05). OS was significantly influenced by the
      type of antecedent pregnancy (molar 98 % vs. others 93 %; p = 0.04), FIGO stage
      (I, II 100 % vs. III, IV 94 %; p = 0.02), score (low-risk 100 % vs. high-risk 92
      %; p = 0.01), and site of metastasis (lung/vagina 98 % vs. others 85 %; p =
      0.002). CONCLUSIONS: GTNs have excellent prognosis if properly treated at
      experienced centers. Single-agent dactinomycin seems more effective for low-risk
      GTN. EMA-CO remains the preferred primary treatment regimen for high-risk group.
      The excellent outcome reflects the success of salvage therapy.

PMID- 25398722
TI  - Barriers and opportunities: a community-based participatory research study of
      health beliefs related to diabetes in a US Marshallese community.
AB  - PURPOSE: This study investigates the beliefs and perceptions related to type 2
      diabetes that influence diabetes self-management behaviors for Marshallese in the
      United States. Using the health belief model as a theoretical framework, the
      researchers seek to better understand the underlying beliefs that motivate or
      impede diabetes self-management behaviors. METHODS: The community-based
      participatory research (CBPR) collaborative engaged in 14 months of preliminary
      fieldwork and conducted 2 tiers of focus groups for this project as part of the
      long-term commitment to reducing health inequalities in the Marshallese
      community. The CBPR team conducted an initial round of 2 exploratory focus groups
      (n = 15). Based on the knowledge gained, researchers held a second round of focus
      groups (n = 13) on health beliefs regarding diabetes. All participants were
      Marshallese, aged 18 years and older, and included men and women. Participants
      either had a diagnosis of diabetes or were a caretaker of someone with diabetes.
      RESULTS: The findings elucidate the structural and nonstructural barriers to
      successful diabetes self-management for Marshallese in the United States.
      Barriers include eating differently from the rest of the family, social stigma of
      diabetes, transportation, cost, lack of access to health care, and cultural and
      language barriers. CONCLUSIONS: While there are significant barriers to improving
      diabetes self-management, there are also areas of opportunity, including family
      and peer reinforcement to encourage proper diabetes management behaviors and a
      growing community desire to lift the stigma of diabetes. The CBPR team offers
      recommendations to make diabetes management interventions more culturally
      appropriate and effective for the Marshallese population.

PMID- 25398723
TI  - Mechanisms of density dependence in ducks: importance of space and per capita
      food.
AB  - The growth rate of populations usually varies over time, often in a density
      dependent manner. Despite the large amount of literature on density dependence,
      relatively little is known of the mechanisms underlying the density-dependent
      processes affecting populations, especially per capita natality. We performed a
      20-year study on the density dependence of brood production in two duck species
      differing in the stability of habitat use. Our study was conducted in a boreal
      watershed in southern Finland. We predicted that a diving duck common goldeneye
      Bucephala clangula, with more stable habitat use, would show stronger density
      dependence than a dabbling duck common teal Anas crecca. We investigated
      reproductive output in relation to the duck pair density per se as well as in
      relation to per capita food availability. As predicted, the reproductive output
      of the goldeneye showed a more density-dependent pattern than that of the teal.
      The number of goldeneye broods per pair decreased when the pair density
      increased. This was not the case with the teal. However, when the breeding
      success was measured by taking into account per capita food availability, both
      species showed density dependence. Our results imply that the occurrence of
      density dependent processes may vary even in sympatric ducks breeding in the
      same, relatively stable landscape. Our analysis also emphasizes that it is
      important to take into account per capita resource availability when studying the
      density dependence of breeding success. Both findings have important implications
      for the management and conservation of species. 

PMID- 25398724
TI  - Trends and patterns of hormonal contraceptive prescribing for adolescents in
      primary care in the U.K.
AB  - BACKGROUND: Hormonal contraceptives are the most common method used worldwide by
      teenagers to prevent unwanted pregnancies. To date there are limited data about
      such use by teenagers in the UK. This study investigated trends and patterns of
      hormonal contraceptive prescribing to adolescents aged 12-18 years in UK primary
      care between 2002 and 2011. METHODS: A retrospective cohort study using the IMS
      Disease Analyzer database was conducted. All females aged 12-18 years with >=1
      prescription for a contraceptive drug between 1 January 2002 and 31 December 2011
      were included. Annual prevalence of contraceptive drug prescribing was
      calculated, and indications for prescribing, and types of contraceptive drug
      prescribed, were examined. RESULTS: In 2002, 13.7% (6135/44 532) of female
      adolescents received prescriptions for hormonal contraceptives, compared to 19.0%
      (6597/34 676) in 2011. The majority of female adolescents [2002: 76.2%
      (4676/6135); 2011: 65.7% (4334/6597)] received a contraceptive drug for
      'contraceptive management'. The combined oral contraceptive (COC),
      'progestogen+estrogen', was the most commonly prescribed. Although use of
      progestogen-only contraceptives was lower than COCs, the number of patients who
      received desogestrel pills and etonogestrel implants increased during the study
      period; levonorgestrel pill use declined. Only one injectable progestogen, long
      acting depot medroxyprogesterone acetate, was prescribed. CONCLUSIONS: Use of
      hormonal contraceptives among adolescents increased between 2002 and 2011, and
      COC usage was dominant. The increasing use of hormonal contraceptives in
      adolescents, especially in younger adolescents, warrants further investigation,
      including research into the long-term safety of these medicines in this age
      group.

PMID- 25398725
TI  - A low-cost cognitive rehabilitation with a commercial video game improves
      sustained attention and executive functions in multiple sclerosis: a pilot study.
AB  - OBJECTIVE: To evaluate the effectiveness of a home-based cognitive rehabilitation
      (CR) program based on the video game Dr Kawashima's Brain Training (DKBT;
      Nintendo, Japan), in improving attention, processing speed, and working memory of
      patients with multiple sclerosis (MS). METHODS: This was a randomized, wait-list
      control study. Patients with MS and failure in at least one between Stroop Test
      (ST), Paced Auditory Serial Addition Test (PASAT), and Symbol Digit Modalities
      Test (SDMT) were submitted to an 8-week home-based CR program playing DKBT.
      Patients were evaluated at baseline and after DKBT by the aforementioned tests,
      by the Modified Fatigue Impact Scale (MFIS) and by the MS Quality of Life-54
      questionnaire (MSQoL-54). RESULTS: Fifty-two 52 patients were screened for
      eligibility; 35 (mean [standard deviation] age of 43.9 [8.4] years, median
      Expanded Disability Status Scale score of 2.0 (range = 2.0-6.0) were randomly
      assigned to the intervention group (n = 18) or wait-list control group (n = 17).
      ANCOVA analysis showed a significant effect of DKBT on ST (F = 5.027; P = .034;
      F(2) = 0.210), SDMT (F = 4.240; P = .049; F(2) = 0.177), and on some subscales of
      MSQoL-54. The PASAT and cognitive subscale of MFIS also showed an improvement,
      but this was just not significant (F = 4.104, P = .054, F(2) = 0.171, and F =
      4.226, P = .054, F(2) = 0.237, respectively). CONCLUSION: We suggest that a home
      based DKBT program may improve cognitive functions, some aspects of QoL, and
      cognitive fatigue in patients with MS.

PMID- 25398726
TI  - Efficacy of Constraint-Induced Movement Therapy in Early Stroke Rehabilitation: A
      Randomized Controlled Multisite Trial.
AB  - BACKGROUND: There is limited evidence for the effects of constraint-induced
      movement therapy (CIMT) in the early stages of stroke recovery. OBJECTIVE: To
      evaluate the effect of a modified CIMT within 4 weeks poststroke. METHODS: This
      single-blinded randomized multisite trial investigated the effects of CIMT in 47
      individuals who had experienced a stroke in the preceding 26 days. Patients were
      allocated to a CIMT or a usual care (control) group. The CIMT program was 3 h/d
      over 10 consecutive working days, with mitt use on the unaffected arm for up to
      90% of waking hours. The follow-up time was 6 months. The primary outcome was the
      Wolf Motor Function test (WMFT) score. Secondary outcomes were the Fugl-Meyer
      upper-extremity motor score, Nine-Hole Peg test (NHPT) score, the arm use ratio,
      and the Stroke Impact Scale. Analyses of covariance with adjustment for baseline
      values were used to assess differences between the groups. RESULTS: After
      treatment, the mean timed WMFT score was significantly better in the CIMT group
      compared with the control group. Moreover, posttreatment dexterity, as tested
      with the NHPT, was significantly better in the CIMT group, whereas the other test
      results were similar in both the groups. At the 6-month follow-up, the 2 groups
      showed no significant difference in arm impairment, function, or use in daily
      activities. CONCLUSIONS: Despite a favorable effect of CIMT on timed movement
      measures immediately after treatment, significant effects were not found after 6
      months.

PMID- 25398728
TI  - Sexual medicine and BASHH.

PMID- 25398727
TI  - Interventions to Reduce Spasticity and Improve Function in People With Chronic
      Incomplete Spinal Cord Injury: Distinctions Revealed by Different Analytical
      Methods.
AB  - BACKGROUND: Spinal cord injury (SCI) results in impaired function, and ankle
      joint spasticity is a common secondary complication. Different interventions have
      been trialed with variable results. OBJECTIVE: We investigated the effects of
      pharmacological and physical (locomotor training) interventions on function in
      people living with incomplete motor function loss caused by SCI and used
      different analytical techniques to understand whether functional levels affect
      recovery with different interventions. METHODS: Participants with an incomplete
      SCI were assigned to 3 groups: no intervention, Lokomat, or tizanidine. Outcome
      measures were the 10-m walk test, 6-minute walk test, and the Timed Up and Go.
      Participants were classified in 2 ways: (1) based on achieving an improvement
      above the minimally important difference (MID) and (2) using growth mixture
      modeling (GMM). Functional levels of participants who achieved the MID were
      compared and random coefficient regression (RCR) was used to assess recovery in
      GMM classes. RESULTS: Overall, walking speed and endurance improved, with no
      difference between interventions. Only a small number of participants achieved
      the MID. Both MID and GMM-RCR analyses revealed that tizanidine improved
      endurance in high-functioning participants. GMM-RCR classification also showed
      that speed and mobility improved after locomotor training. CONCLUSIONS:
      Improvements in function were achieved in a limited number of people with SCI.
      Using the MID and GMM techniques, differences in responses to interventions
      between high-and low-functioning participants could be identified. These
      techniques may, therefore, have potential to be used for characterizing
      therapeutic effects resulting from different interventions.

PMID- 25398729
TI  - Why are anogenital warts diagnoses decreasing in the U.K.: bivalent human
      papillomavirus (HPV) vaccine cross-protection or failure to examine?

PMID- 25398730
TI  - HIV testing in pregnancy.

PMID- 25398732
TI  - Considerations on an approach for establishing a framework for bioactive food
      components.
AB  - Bioactive food components have shown potential health benefits for more than a
      decade. Currently there are no recommended levels of intake [i.e., Dietary
      Reference Intakes (DRIs)] as there are for nutrients and fiber. DRIs for
      essential nutrients were based on requirements for each specific nutrient to
      maintain normal physiologic or biochemical function and to prevent signs of
      deficiency and adverse clinical effects. They were later expanded to include
      criteria for reducing the risk of chronic degenerative diseases for some
      nutrients. There are many challenges for establishing recommendations for intakes
      of nonessential food components. Although some nonessential food components have
      shown health benefits and are safe, validated biomarkers of disease risk
      reduction are lacking for many. Biomarkers of intake (exposure) are limited in
      number, especially because the bioactive compounds responsible for beneficial
      effects have not yet been identified or are unknown. Furthermore, given this lack
      of characterization of composition in a variety of foods, it is difficult to
      ascertain intakes of nonessential food components, especially with the use of
      food-frequency questionnaires designed for estimating intakes of nutrients.
      Various intermediary markers that may predict disease outcome have been used as
      functional criteria in the DRI process. However, few validated surrogate
      endpoints of chronic disease risk exist. Nonvalidated intermediary biomarkers of
      risk may possibly predict clinical outcomes, but more research is needed to
      confirm the associations between cause and effect. One criterion for establishing
      acceptable intermediary outcome indicators may be the maintenance of normal
      physiologic function throughout adulthood, which presumably would lead to reduced
      chronic disease risk. Multiple biomarkers of outcomes that demonstrate the same
      health benefit may also be helpful. It would be beneficial to continue to refine
      the process of setting DRIs by convening a workshop on establishing a framework
      for nonessential food components that would take into consideration intermediary
      biomarkers indicative of optimal health.

PMID- 25398731
TI  - Nutrition implications for fetal alcohol spectrum disorder.
AB  - Prenatal alcohol exposure produces a multitude of detrimental alcohol-induced
      defects in children collectively known as fetal alcohol spectrum disorder (FASD).
      Children with FASD often exhibit delayed or abnormal mental, neural, and physical
      growth. Socioeconomic status, race, genetics, parity, gravidity, age, smoking,
      and alcohol consumption patterns are all factors that may influence FASD. Optimal
      maternal nutritional status is of utmost importance for proper fetal development,
      yet is often altered with alcohol consumption. It is critical to determine a
      means to resolve and reduce the physical and neurological malformations that
      develop in the fetus as a result of prenatal alcohol exposure. Because there is a
      lack of information on the role of nutrients and prenatal nutrition interventions
      for FASD, the focus of this review is to provide an overview of nutrients
      (vitamin A, docosahexaenoic acid, folic acid, zinc, choline, vitamin E, and
      selenium) that may prevent or alleviate the development of FASD. Results from
      various nutrient supplementation studies in animal models and FASD-related
      research conducted in humans provide insight into the plausibility of prenatal
      nutrition interventions for FASD. Further research is necessary to confirm
      positive results, to determine optimal amounts of nutrients needed in
      supplementation, and to investigate the collective effects of multiple-nutrient
      supplementation.

PMID- 25398733
TI  - Undernutrition, the acute phase response to infection, and its effects on
      micronutrient status indicators.
AB  - Infection and undernutrition are prevalent in developing countries and
      demonstrate a synergistic relation. Undernutrition increases infection-related
      morbidity and mortality. The acute phase response (APR) is an innate, systemic
      inflammatory reaction to a wide array of disruptions in a host's homeostasis,
      including infection. Released from immune cells in response to deleterious
      stimuli, proinflammatory cytokines act on distant tissues to induce behavioral
      (e.g., anorexia, weakness, and fatigue) and systemic effects of the APR.
      Cytokines act to increase energy and protein requirements to manifest fever and
      support hepatic acute phase protein (APP) production. Blood concentrations of
      glucose and lipid are augmented to provide energy to immune cells in response to
      cytokines. Additionally, infection decreases intestinal absorption of nutrients
      and can cause direct loss of micronutrients. Traditional indicators of iron,
      zinc, and vitamin A status are altered during the APR, leading to inaccurate
      estimations of deficiency in populations with a high or unknown prevalence of
      infection. Blood concentrations of APPs can be measured in nutrition
      interventions to assess the time stage and severity of infection and correct for
      the APR; however, standardized cutoffs for nutrition applications are needed.
      Protein-energy malnutrition leads to increased gut permeability to pathogens,
      abnormal immune cell populations, and impaired APP response. Micronutrient
      deficiencies cause specific immune impairments that affect both innate and
      adaptive responses. This review describes the antagonistic interaction between
      the APR and nutritional status and emphasizes the need for integrated
      interventions to address undernutrition and to reduce disease burden in
      developing countries.

PMID- 25398736
TI  - Carbohydrates.

PMID- 25398734
TI  - Sodium-to-potassium ratio and blood pressure, hypertension, and related factors.
AB  - The potential cost-effectiveness and feasibility of dietary interventions aimed
      at reducing hypertension risk are of considerable interest and significance in
      public health. In particular, the effectiveness of restricted sodium or increased
      potassium intake on mitigating hypertension risk has been demonstrated in
      clinical and observational research. The role that modified sodium or potassium
      intake plays in influencing the renin-angiotensin system, arterial stiffness, and
      endothelial dysfunction remains of interest in current research. Up to the
      present date, no known systematic review has examined whether the sodium-to
      potassium ratio or either sodium or potassium alone is more strongly associated
      with blood pressure and related factors, including the renin-angiotensin system,
      arterial stiffness, the augmentation index, and endothelial dysfunction, in
      humans. This article presents a systematic review and synthesis of the randomized
      controlled trials and observational research related to this issue. The main
      findings show that, among the randomized controlled trials reviewed, the sodium
      to-potassium ratio appears to be more strongly associated with blood pressure
      outcomes than either sodium or potassium alone in hypertensive adult populations.
      Recent data from the observational studies reviewed provide additional support
      for the sodium-to-potassium ratio as a superior metric to either sodium or
      potassium alone in the evaluation of blood pressure outcomes and incident
      hypertension. It remains unclear whether this is true in normotensive populations
      and in children and for related outcomes including the renin-angiotensin system,
      arterial stiffness, the augmentation index, and endothelial dysfunction. Future
      study in these populations is warranted.

PMID- 25398737
TI  - Centers for Disease Control and Prevention. State indicator report on Physical
      Activity, 2014. Atlanta, GA: U.S. Department of Health and Human Services; 2014.

PMID- 25398735
TI  - An integrative review of sleep for nutrition professionals.
AB  - Sleep is an essential lifestyle factor that contributes to overall health. The
      inverse relation between sleep duration and weight status has revealed the
      importance of sleep in nutritional health. This integrative review builds
      foundational knowledge with regard to sleep vis-a-vis nutrition by summarizing
      the importance and process of sleep, current sleep recommendations and trends, as
      well as lifestyle contributors to poor sleep. Additionally, it details the
      association between sleep and obesity and potential mechanisms for this
      association. Furthermore, guidance is offered regarding the incorporation of
      sleep considerations in nutrition counseling, communication, and research. Like
      many other lifestyle factors that contribute to nutritional health, sleep needs
      to be considered when examining weight management and health promotion.

PMID- 25398738
TI  - The science upon which to base dietary sodium policy.
AB  - Few nutrient intake recommendations become subjects of heated scientific debate,
      but sodium is 1 of them. In the absence of sufficient clinical trials focused on
      sodium intake and health outcomes, studies that used the surrogate marker of
      blood pressure have been used to support extreme sodium reduction. Under tightly
      controlled conditions, maximum achievable sodium reduction leads to a 1-6 mm Hg
      reduction in systolic blood pressure, which presumably leads to reduced
      cardiovascular disease morbidity and mortality. However, in observational cohort
      studies that used not blood pressure but actual health conditions as outcomes,
      the presumed relation between sodium intakes <2500 mg/d was not observed. Thus,
      the blood pressure effect of sodium restriction can no longer be accepted as a
      surrogate for health outcomes associated with sodium intake. Evidence that
      reducing sodium intakes to <2500 mg/d will improve health is needed to justify
      continuing efforts to modify diet.

PMID- 25398739
TI  - At the dawn of a new discovery: the potential of breast milk stem cells.
AB  - Breast milk contains bioactive molecules that provide a multitude of immunologic,
      developmental and nutritional benefits to the infant. Less attention has been
      placed on the cellular nature of breast milk, which contains thousands to
      millions of maternal cells in every milliliter that the infant ingests. What are
      the properties and roles of these cells? Most studies have examined breast milk
      cells from an immunologic perspective, focusing specifically on the leukocytes,
      mainly in the early postpartum period. In the past decade, research has taken a
      multidimensional approach to investigating the cells of human milk. Technologic
      advances in single cell analysis and imaging have aided this work, which has
      resulted in the breakthrough discovery of stem cells in breast milk with
      multilineage potential that are transferred to the offspring during
      breastfeeding. This has generated numerous implications for both infant and
      maternal health and regenerative medicine. This review summarizes the latest
      knowledge on breast milk stem cells, and discusses their known in vitro and in
      vivo attributes as well as potential functions and applications.

PMID- 25398740
TI  - The origin of human milk bacteria: is there a bacterial entero-mammary pathway
      during late pregnancy and lactation?
AB  - Human milk is a source of bacteria to the infant gut; however, the origin of milk
      bacteria, as well as their impact on neonatal gut microbiota establishment,
      remains largely unknown. In the past years, results provided by different
      research groups suggest that certain bacteria from the maternal gastrointestinal
      tract could translocate through a mechanism involving mononuclear immune cells,
      migrate to the mammary glands via an endogenous cellular route (the bacterial
      entero-mammary pathway), and subsequently colonize the gastrointestinal tract of
      the breast-fed neonate. If such findings are confirmed in the future, we could
      exert a positive influence on infant health by modulating the maternal gut
      microbiota. 

PMID- 25398741
TI  - The use of metabolomics in population-based research.
AB  - The NIH has made a significant commitment through the NIH Common Fund's
      Metabolomics Program to build infrastructure and capacity for metabolomics
      research, which should accelerate the field. Given this investment, it is the
      ideal time to start planning strategies to capitalize on the infrastructure being
      established. An obvious gap in the literature relates to the effective use of
      metabolomics in large-population studies. Although published reports from
      population-based studies are beginning to emerge, the number to date remains
      relatively small. Yet, there is great potential for using metabolomics in
      population-based studies to evaluate the effects of nutritional, pharmaceutical,
      and environmental exposures (the "exposome"); conduct risk assessments; predict
      disease development; and diagnose diseases. Currently, the majority of the
      metabolomics studies in human populations are in nutrition or nutrition-related
      fields. This symposium provided a timely venue to highlight the current state-of
      science on the use of metabolomics in population-based research. This session
      provided a forum at which investigators with extensive experience in performing
      research within large initiatives, multi-investigator grants, and epidemiology
      consortia could stimulate discussion and ideas for population-based metabolomics
      research and, in turn, improve knowledge to help devise effective methods of
      health research.

PMID- 25398742
TI  - Modifying eating behavior: novel approaches for reducing body weight, preventing
      weight regain, and reducing chronic disease risk.
AB  - This article is a summary of the symposium "Modifying Eating Behavior: Novel
      Approaches for Reducing Body Weight, Preventing Weight Regain, and Reducing
      Chronic Disease Risk" held 29 April 2014 at the ASN Scientific Sessions and
      Annual Meeting at Experimental Biology 2014 in San Diego, CA. In this symposium,
      novel approaches to modifying eating behavior were highlighted, including 1)
      alteration of meal timing and macronutrient composition and 2) retraining and
      provision of feedback about eating behavior. Dr. Ciampolini discussed a method
      for teaching individuals to recognize a decrease in blood glucose concentration,
      and therefore the need for energy, by learning the associated physical sensations
      (signifying hunger). Dr. Madar and Sigal Sofer presented their work on reducing
      hunger during energy reduction by feeding carbohydrate only in the evening. Dr.
      Hamilton-Shield reviewed studies on the Mandometer (Mikrodidakt), a device for
      training individuals to slow eating rate. Finally, Dr. Sazonov presented
      information on a wearable device, the Automatic Ingestion Monitor, which senses
      jaw motion and/or hand-to-mouth gestures to detect and characterize food intake.
      His goal is to use the instrument to prevent overeating by providing feedback to
      the user to stop ingestion at a predetermined limit.

PMID- 25398743
TI  - Nutrimetabolomics.
AB  - Metabolic pathways are tightly regulated in a tissue-specific manner to maintain
      whole-body homeostasis. Nutrients and hormones control these pathways at the
      level of transcription, translation, and/or post-translation. Genomic and
      proteomic tools have been predominantly used to understand metabolic regulation,
      and only a few studies used metabolomics approaches. Metabolomics is a powerful,
      unbiased approach that allows comprehensive metabolic analysis of physiologic
      measurements and energy balance. Thus, nutrimetabolomics can expedite our ability
      to identify metabolic diseases that are influenced by nutrients and to develop
      targeted diet-based treatments. Presentations at this symposium reviewed current
      resources and platforms for metabolic profiling along with statistical and
      bioinformatics tools for data and pathway analyses. Specific applications of
      metabolomics were illustrated in nutritional and disease conditions, including
      polycystic ovary syndrome, diabetes, and obesity and in host-gut microbiome
      interactions.

PMID- 25398744
TI  - Successful scientist: What's the winning formula?
AB  - What does it take to become a successful scientist? This question is usually
      asked or thought about at some point in a young scientist's career. The early
      stages of a scientific career are fraught with many hardships, and achieving
      success can seem impossible and daunting. After encountering many obstacles, it
      becomes easy to focus on failures and lose sight of career goals. The journey to
      success can seem so simple when looked upon from the outside, but even the best
      scientists have endured many hardships, which are often not communicated. This
      educational symposium featured a diverse panel of 5 accomplished scientists
      representing different work environments, such as government, industry, and
      academia. They discussed tips on how to have a successful career journey and the
      key qualities of a successful scientist. Also, they revealed the secret to what's
      in the winning formula for success.

PMID- 25398745
TI  - Sugar-sweetened and artificially-sweetened beverages in relation to obesity risk.
AB  - The goal of this review was to critically evaluate the scientific evidence in
      humans on the potential effect of sweetened beverages on weight gain and risk of
      obesity in youth and adults. Two categories of these beverages were reviewed.
      Sugar-sweetened beverages (SSBs) include soft drinks, colas, other sweetened
      carbonated beverages, and fruit drinks with added sugar. Artificially sweetened
      beverages (ASBs), also referred to as non-nutritive sweetened beverages, are
      marketed and used as a replacement for SSBs for those who want to reduce sugar
      and caloric intake. The totality of evidence to date demonstrates a pattern
      across observational and experimental studies of an increased risk of weight gain
      and obesity with higher intake of SSBs. However, it remains difficult to
      establish the strength of the association and the independence from other
      potentially confounding factors. The primary reason for unclear conclusions
      regarding the robustness of any effect of SSBs is due to the heterogeneity and
      methodologic limitations of both observational and experimental studies on this
      topic. Although some observational studies have suggested that ASBs may cause
      increased risk of obesity and cardiometabolic diseases, there is no clear
      mechanism for this pathway, and the epidemiologic studies are highly
      inconsistent. An important issue with the observational studies on ASBs and
      obesity or disease risk is reverse causality bias, with higher-quality studies
      demonstrating this possibility. The field needs higher-quality experimental
      studies in humans, with relevant direct comparisons between sweetened beverages
      and their sweetened solid-food alternatives.

PMID- 25398747
TI  - Food prices and obesity: a review.
AB  - In response to rising rates of obesity in the United States due in part to excess
      food consumption, researchers and policy makers have argued that levying food
      taxes on obesity-promoting foods, perhaps combined with subsidies on healthier
      options, would be an effective tool to stem the obesity epidemic. The extent to
      which overall energy intake or weight outcomes will improve as a result of these
      policies is ultimately an empirical question. This review examines the link
      between food or beverage price changes and energy intake or weight outcomes among
      U.S. consumers. Current evidence indicates that, by themselves, targeted food
      taxes and subsidies as considered to date are unlikely to have a major effect on
      individual weight or obesity prevalence. While research suggests that the effects
      are modest, food taxes and subsidies may play an important role in a multifaceted
      approach to reducing obesity incidence.

PMID- 25398746
TI  - Food availability/convenience and obesity.
AB  - Neighborhood environments have received considerable attention in recent local,
      state, and national obesity prevention initiatives, with a particular focus on
      food deserts, or areas with poor access to healthy foods. Yet, there are
      inconsistencies in the evidence base, suggesting a nuanced association between
      neighborhood environment, food availability, diet behaviors, and obesity. There
      is heterogeneity in associations between environmental exposures and health
      outcomes across race/ethnicity, gender, region, and urbanicity, which results in
      complexity in the interpretation of findings. There are several limitations in
      the literature, including a predominance of cross-sectional studies, reliance on
      commercial business listings, lack of attention to the process by which diet
      resources are established and expanded within neighborhoods and the potential for
      individuals to selectively migrate to locate near such facilities, a predominant
      focus on residential neighborhoods, and lack of information about the decision
      making process underlying purchasing patterns. More research is needed to address
      the complexity of individual-level residential decision making as well as the
      purposeful placement of food environment resources across social and geographic
      space using longitudinal data and complex statistical approaches. In addition,
      improvements in data quality and depth related to food access and availability
      are needed, including behavioral data on purchase patterns and interactions with
      the food environment, and greater attention to heterogeneity across
      subpopulations. As policy changes to the food environment move forward, it is
      critical that there is rigorous and scientific evaluation of environmental
      changes and their impact on individual-level diet choices and behaviors, and
      their further influence on body weight.

PMID- 25398748
TI  - Evidence for efficacy and effectiveness of changes in eating frequency for body
      weight management.
AB  - In self-reported diets of free living individuals, frequent eating is associated
      with higher energy intake, yet beliefs about the possible beneficial effect of
      higher eating frequency for managing body weight persist. Prospective cohort
      studies and controlled trials of manipulation of eating frequency published by 31
      December 2012 were reviewed to assess whether variation in eating frequency may
      be an adjunct to weight management. Four prospective cohort studies were
      identified; 2 of these included adults followed for 10 y and 2 followed pre
      adolescent/adolescent girls for 6 or 10 y. Within each age category, the findings
      of the 2 studies were contradictory. Six controlled trials with adult subjects
      serving as their own controls found no significant changes in body weight due to
      manipulation of eating frequency interventions lasting 6-8 wk. In 6 additional
      intervention trials of 8-52 wk duration, free-living adults were counseled to
      change the eating frequency of self-selected food intake with no significant
      differences in weight loss attributable to eating frequency. Overall, the
      consistency of the null findings from controlled trials of manipulation of eating
      frequency for promoting weight loss suggests that beliefs about the role of
      higher eating frequency in adult weight management are not supported by evidence.
      Interpretation of the evidence from published observational studies is
      complicated by differences in definition of eating frequency and limited
      knowledge of systematic and random errors in measurement of eating frequency.

PMID- 25398749
TI  - Portion size and obesity.
AB  - Portion size is a key environmental driver of energy intake, and larger-than
      appropriate portion sizes could increase the risk of weight gain. Multiple acute,
      well-controlled laboratory studies, supported by data from free-living settings,
      demonstrated that portion size has a powerful and proportionate effect on the
      amount of food consumed. Of particular importance is that bouts of overeating
      associated with large portions are sustained and not followed by a compensatory
      reduction in energy intake. The positive effect of portion size on energy intake
      was demonstrated for different types of foods and beverages, and is particularly
      pronounced with energy-dense foods. The predisposition to overeat in response to
      large portions is pervasive and occurs regardless of demographic characteristics,
      such as socioeconomic status, age, body mass index, and sex. Secular trends
      toward greater availability of large portions, coupled with value-size pricing,
      effectively distorted consumption norms and perceptions of what is an appropriate
      amount to eat. Nevertheless, although a direct causal link between portion size
      and obesity remains to be established, advice to moderate portion sizes,
      especially of energy-dense foods, is presently the cornerstone of most weight
      management advice. Although many strategies have been proposed to counteract the
      deleterious effects of portion size, there are few data indicating which are
      likely to be acceptable in the medium- to long term. Further research is urgently
      needed to establish what types of interventions targeted at portion size are
      likely to be effective, in what settings, and among which target groups.

PMID- 25398750
TI  - Energy density, energy intake, and body weight regulation in adults.
AB  - The role of dietary energy density (ED) in the regulation of energy intake (EI)
      is controversial. Methodologically, there is also debate about whether beverages
      should be included in dietary ED calculations. To address these issues, studies
      examining the effects of ED on EI or body weight in nonelderly adults were
      reviewed. Different approaches to calculating dietary ED do not appear to alter
      the direction of reported relations between ED and body weight. Evidence that
      lowering dietary ED reduces EI in short-term studies is convincing, but there are
      currently insufficient data to determine long-term effectiveness for weight loss.
      The review also identified key barriers to progress in understanding the role of
      ED in energy regulation, in particular the absence of a standard definition of
      ED, and the lack of data from multiple long-term clinical trials examining the
      effectiveness of low-ED diet recommendations for preventing both primary weight
      gain and weight regain in nonobese individuals. Long-term clinical trials
      designed to examine the impact of dietary ED on energy regulation, and including
      multiple ED calculation methods within the same study, are still needed to
      determine the importance of ED in the regulation of EI and body weight. 

PMID- 25398755
TI  - Fundamentals of translational neuroscience in toxicologic pathology: optimizing
      the value of animal data for human risk assessment.
AB  - A half-day Society of Toxicologic Pathology continuing education course on
      "Fundamentals of Translational Neuroscience in Toxicologic Pathology" presented
      some current major issues faced when extrapolating animal data regarding
      potential neurological consequences to assess potential human outcomes. Two talks
      reviewed functional-structural correlates in rodent and nonrodent mammalian
      brains needed to predict behavioral consequences of morphologic changes in
      discrete neural cell populations. The third lecture described practical steps for
      ensuring that specimens from rodent developmental neurotoxicity tests will be
      processed correctly to produce highly homologous sections. The fourth talk
      detailed demographic factors (e.g., species, strain, sex, and age); physiological
      traits (body composition, brain circulation, pharmacokinetic/pharmacodynamic
      patterns, etc.); and husbandry influences (e.g., group housing) known to alter
      the effects of neuroactive agents. The last presentation discussed the
      appearance, unknown functional effects, and potential relevance to humans of
      polyethylene glycol (PEG)-associated vacuoles within the choroid plexus
      epithelium of animals. Speakers provided real-world examples of challenges with
      data extrapolation among species or with study design considerations that may
      impact the interpretability of results. Translational neuroscience will be
      bolstered in the future as less invasive and/or more quantitative techniques are
      devised for linking overt functional deficits to subtle anatomic and chemical
      lesions. 

PMID- 25398751
TI  - Variety, palatability, and obesity.
AB  - Among the key characteristics of the Western obesogenic food environment is a
      highly palatable and varied food supply. Laboratory investigations of eating
      behavior in both humans and animals established key roles for palatability and
      variety in stimulating appetite, delaying satiety, and promoting excessive energy
      intake. There is a robust effect of food palatability and variety on short-term
      food intake, and increased variety and palatability also cause weight gain in
      animal models. However, laboratory paradigms do not replicate the complexities of
      eating in a natural setting, and there is a shortage of evidence to estimate the
      magnitude of effects on weight in humans. There are substantial individual
      differences in susceptibility to the palatability effect and this may be a key
      determinant in individual vulnerability to weight gain. The understanding of
      pathways through which palatability and variety can affect eating is advancing,
      and epidemiologic and intervention studies are needed to translate laboratory
      findings into applications in public health or clinical domains, and to establish
      whether there is a role for greater regulation of the food environment in
      tackling increases in obesity.

PMID- 25398754
TI  - The evidence for alpha-linolenic acid and cardiovascular disease benefits:
      Comparisons with eicosapentaenoic acid and docosahexaenoic acid.
AB  - Our understanding of the cardiovascular disease (CVD) benefits of alpha-linolenic
      acid (ALA, 18:3n-3) has advanced markedly during the past decade. It is now
      evident that ALA benefits CVD risk. The expansion of the ALA evidence base has
      occurred in parallel with ongoing research on eicosapentaenoic acid (EPA, 20:5n
      3) and docosahexaenoic acid (DHA, 22:6n-3) and CVD. The available evidence
      enables comparisons to be made for ALA vs. EPA + DHA for CVD risk reduction. The
      epidemiologic evidence suggests comparable benefits of plant-based and marine
      derived n-3 (omega-3) PUFAs. The clinical trial evidence for ALA is not as
      extensive; however, there have been CVD event benefits reported. Those that have
      been reported for EPA + DHA are stronger because only EPA + DHA differed between
      the treatment and control groups, whereas in the ALA studies there were diet
      differences beyond ALA between the treatment and control groups. Despite this,
      the evidence suggests many comparable CVD benefits of ALA vs. EPA + DHA. Thus, we
      believe that it is time to revisit what the contemporary dietary recommendation
      should be for ALA to decrease the risk of CVD. Our perspective is that increasing
      dietary ALA will decrease CVD risk; however, randomized controlled clinical
      trials are necessary to confirm this and to determine what the recommendation
      should be. With a stronger evidence base, the nutrition community will be better
      positioned to revise the dietary recommendation for ALA for CVD risk reduction.

PMID- 25398756
TI  - Successful integration of nonclinical and clinical findings in interpreting the
      clinical relevance of rodent neoplasia with a new chemical entity.
AB  - Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been
      developed for the treatment of adults with type 2 diabetes mellitus (T2DM).
      During the phase 3 program, treatment-related pheochromocytomas, renal tubular
      tumors, and testicular Leydig cell tumors were reported in the 2-year rat
      toxicology study. Treatment-related tumors were not seen in the 2-year mouse
      study. A cross-functional, mechanism-based approach was undertaken to determine
      whether the mechanisms responsible for tumorigenesis in the rat were of relevance
      to humans. Based on findings from nonclinical and clinical studies, the treatment
      related tumors observed in rats were not deemed to be of clinical relevance.
      Here, we describe the scientific and regulatory journey from learning of the 2
      year rat study findings to the approval of canagliflozin for the treatment of
      T2DM.

PMID- 25398758
TI  - Right coronary artery to coronary sinus fistula.

PMID- 25398757
TI  - Perfluorooctanoic Acid (PFOA)-induced Liver Lesions in Two Strains of Mice
      Following Developmental Exposures: PPARalpha Is Not Required.
AB  - Perfluorooctanoic acid (PFOA) is a ubiquitous pollutant that causes liver
      toxicity in rodents, a process believed to be dependent on peroxisome
      proliferator-activated receptor-alpha (PPARalpha) activation. Differences between
      humans and rodents have made the human relevance of some health effects caused by
      PFOA controversial. We analyzed liver toxicity at 18 months following gestational
      PFOA exposure in CD-1 and 129/Sv strains of mice and compared PFOA-induced
      effects between strains and in wild type (WT) and PPARalpha-knockout (KO) 129/Sv
      mice. Pregnant mice were exposed daily to doses (0.01-5 mg/kg/BW) of PFOA from
      gestation days 1 to 17. The female offspring were necropsied at 18 months, and
      liver sections underwent a full pathology review. Hepatocellular adenomas formed
      in PFOA-exposed PPARalpha-KO 129/Sv and CD-1 mice and were absent in untreated
      controls from those groups and WT 129/Sv. Hepatocellular hypertrophy was
      significantly increased by PFOA exposure in CD-1, and an increased severity was
      found in WT 129/Sv mice. PFOA significantly increased nonneoplastic liver lesions
      in PPARalpha-KO mice (hepatocyte hypertrophy, bile duct hyperplasia, and
      hematopoietic cell proliferation). Low-dose gestational exposures to PFOA induced
      latent PPARalpha-independent liver toxicity that was observed in aged mice.
      Evidence of liver toxicity in PPARalpha-KO mice warrants further investigation
      into PPARalpha-independent pathways. 

PMID- 25398759
TI  - Christopher Boorse and the philosophy of medicine.

PMID- 25398760
TI  - A second rebuttal on health.
AB  - This essay replies to critics since 1995 of my "biostatistical theory" (BST) of
      health. According to the BST, a pathological condition is a state of
      statistically species-subnormal biological part-functional ability, relative to
      sex and age. Theoretical health, the total absence of pathological conditions, is
      then a value-free scientific notion. Recent critics offer a mixture of old and
      new objections to this analysis. Some new ones relate to choice of reference
      class, situation-specificity of function, common diseases and healthy
      populations, improvements in population health, the practice of pathologists,
      "Cambridge changes" in health status, and comparative vs. absolute health
      concepts. I make no changes in doctrine, except to consider treating "normal
      aging" as pathological by taking young adults as the standard for all adults. 

PMID- 25398764
TI  - Relationship of apelin, procalcitonin, and fetuin-A concentrations with carotid
      intima-media thickness in acromegaly.
AB  - BACKGROUND: Acromegaly is characterized by excess growth hormone and insulin-like
      growth factor-1 concentrations. There is conflicting evidence as to whether
      acromegaly is associated with an increased risk of atherosclerosis. Apelin is an
      adipose tissue-derived peptide that may be associated with hyperinsulinemia.
      Fetuin-A is a hepatocyte produced plasma glycoprotein that has an important role
      as a calcification inhibitor. The aim of this study was to examine apelin, fetuin
      A, and procalcitonin concentrations and to assess their relationship with carotid
      intima medial thickness (cIMT) in subjects with acromegaly. METHODS: Apelin,
      fetuin-A, and procalcitonin serum concentrations were measured in 37 (20 inactive
      and 17 active) subjects with acromegaly and 30 control subjects, along with
      carotid intima medial thickness. RESULTS: The concentrations of apelin, fetuin-A,
      and procalcitonin were increased in subjects with acromegaly. There were
      significant correlations between apelin, fetuin-A, and procalcitonin in subjects
      with acromegaly. Carotid intima medial thickness values were similar between
      control subjects and subjects with acromegaly. CONCLUSIONS: Carotid intima medial
      thickness was not increased in subjects with acromegaly. It is possible that the
      increased apelin and fetuin-A concentrations observed play a protective role
      against the development of atherosclerosis in subjects with acromegaly.

PMID- 25398766
TI  - Validation of the long-term assessment of hypothalamic-pituitary-adrenal activity
      in rats using hair corticosterone as a biomarker.
AB  - The evaluation of chronic activity of the hypothalamic-pituitary-adrenal (HPA)
      axis is critical for determining the impact of chronic stressful situations.
      However, current methods have important limitations. The potential use of hair
      glucocorticoids as a noninvasive retrospective biomarker of long-term HPA
      activity is gaining acceptance in humans and wild animals. However, there is no
      study examining hair corticosterone (HC) in laboratory animals. The present study
      validates a method for measuring HC in rats and demonstrates that it properly
      reflects chronic HPA activity. The HC concentration was similar in male and
      female rats, despite higher total plasma corticosterone levels in females,
      tentatively suggesting that it reflects free rather than total plasma
      corticosterone. Exposure of male rats to 2 different chronic stress protocols
      (chronic immobilization and chronic unpredictable stress) resulted in similarly
      higher HC levels compared to controls (1.8-fold). HC also increased after a mild
      chronic stressor (30 min daily restraint). Chronic administration of 2 different
      doses of a long-acting ACTH preparation dramatically increased HC (3.1- and 21.5
      fold, respectively), demonstrating that a ceiling effect in HC accumulation is
      unlikely under other more natural conditions. Finally, adrenalectomy
      significantly reduced HC. In conclusion, HC measurement in rats appears
      appropriate to evaluate integrated chronic changes in circulating corticosterone.

PMID- 25398765
TI  - The transcriptional corepressor MTGR1 regulates intestinal secretory lineage
      allocation.
AB  - Notch signaling largely determines intestinal epithelial cell fate. High Notch
      activity drives progenitors toward absorptive enterocytes by repressing secretory
      differentiation programs, whereas low Notch permits secretory cell assignment.
      Myeloid translocation gene-related 1 (MTGR1) is a transcriptional corepressor in
      the myeloid translocation gene/Eight-Twenty-One family. Given that Mtgr1(-/-)
      mice have a dramatic reduction of intestinal epithelial secretory cells, we
      hypothesized that MTGR1 is a key repressor of Notch signaling. In support of
      this, transcriptome analysis of laser capture microdissected Mtgr1(-/-)
      intestinal crypts revealed Notch activation, and secretory markers Mucin2,
      Chromogranin A, and Growth factor-independent 1 (Gfi1) were down-regulated in
      Mtgr1(-/-) whole intestines and Mtgr1(-/-) enteroids. We demonstrate that MTGR1
      is in a complex with Suppressor of Hairless Homolog, a key Notch effector, and
      represses Notch-induced Hairy/Enhancer of Split 1 activity. Moreover,
      pharmacologic Notch inhibition using a gamma-secretase inhibitor (GSI) rescued
      the hyperproliferative baseline phenotype in the Mtgr1(-/-) intestine and
      increased production of goblet and enteroendocrine lineages in Mtgr1(-/-) mice.
      GSI increased Paneth cell production in wild-type mice but failed to do so in
      Mtgr1(-/-) mice. We determined that MTGR1 can interact with GFI1, a
      transcriptional corepressor required for Paneth cell differentiation, and repress
      GFI1 targets. Overall, the data suggest that MTGR1, a transcriptional corepressor
      well characterized in hematopoiesis, plays a critical role in intestinal lineage
      allocation.

PMID- 25398767
TI  - STAT3 governs hyporesponsiveness and granzyme B-dependent suppressive capacity in
      human CD4+ T cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) integrates key signals
      of cell surface immune receptors, yet its precise role in cluster of
      differentiation (CD)4(+) T cells is not well-established. Current research has
      indicated T-helper cell 17-inducing roles but also tolerogenic roles. To address
      this issue, human T cells were transduced with the constitutively active STAT3
      mutant STAT3C. Following stimulation, STAT3C(+) T cells up-regulated IL-10 (4.1
      +/- 0.5-fold; P < 0.001) and granzyme B (2.5 +/- 1.2, P < 0.05) secretion,
      combined with significantly reduced IFN-gamma (35 +/- 5%), IL-2 (57 +/- 4%), TNF
      alpha (64 +/- 8%), and IL-13 (89 +/- 3%) secretion (P < 0.001). CD3/CD2- or
      CD3/CD28-activated STAT3C(+) T cells revealed reduced proliferation (53.4 +/-
      23.5% and 70.5 +/- 10.4%, respectively), which was independent of IL-10
      production and significantly suppressed effector T cell proliferation by 68.7 +/-
      10.6% and 65.9 +/- 2.6%, respectively (P < 0.001). Phenotypically, STAT3C
      transgenic CD4(+) T cells resembled effector T cells regarding expression of T
      regulatory cell markers, but up-regulated granzyme B expression levels by 2.4
      fold (P < 0.05). Suppression was cell contact dependent and mediated by granzyme
      B-induced cell death, but was independent of IL-10 and TGF-beta. Notably,
      peripheral blood CD4(+)CD45RA(-)lymphocyte activation gene-3(+)CD49(+) type 1
      regulatory T cells revealed activation-induced hyperphosphorylation of STAT3. In
      agreement, pharmacological inhibition of STAT3 activation partially reverted
      hyporesponsiveness of peripheral type 1 regulatory T cells (increasing their
      division index from 0.46 +/- 0.11 to 0.89 +/- 0.04; P < 0.01). These observations
      indicate a clear-cut relation between activation of STAT3 and the acquisition of
      a tolerogenic program, which is also used by peripheral blood type 1 regulatory T
      cells.

PMID- 25398768
TI  - Lysophosphatidate signaling stabilizes Nrf2 and increases the expression of genes
      involved in drug resistance and oxidative stress responses: implications for
      cancer treatment.
AB  - The present work elucidates novel mechanisms for lysophosphatidate (LPA)-induced
      chemoresistance using human breast, lung, liver, and thyroid cancer cells. LPA
      (0.5-10 MUM) increased Nrf2 transcription factor stability and nuclear
      localization by <=5-fold. This involved lysophosphatidate type 1 (LPA1) receptors
      as identified with 1 MUM wls-31 (LPA1/2 receptor agonist) and blocking this
      effect with 20 MUM Ki16425 (LPA1-3 antagonist, Ki = 0.34 MUM). Knockdown of LPA1
      by 50% to 60% with siRNA decreased Nrf2 stability and expressing LPA1, but not
      LPA2/3, in human HepG2 cells increased Nrf2 stabilization. LPA-induced Nrf2
      expression increased transcription of multidrug-resistant transporters and
      antioxidant genes by 2- to 4-fold through the antioxidant response element. This
      protected cells from doxorubicin-induced death. This pathway was verified in vivo
      by orthotopic injection of 20,000 mouse 4T1 breast cancer cells into syngeneic
      mice. Blocking LPA production with 10 mg/kg per d ONO-8430506 (competitive
      autotaxin inhibitor, IC90 = 100 nM) decreased expression of Nrf2, multidrug
      resistant transporters, and antioxidant genes in breast tumors by <=90%.
      Combining 4 mg/kg doxorubicin every third day with ONO-8430506 synergistically
      decreased tumor growth and metastasis to lungs and liver by >70%, whereas
      doxorubicin alone had no significant effect. This study provides the first
      evidence that LPA increases antioxidant gene and multidrug-resistant transporter
      expression. Blocking this aspect of LPA signaling provides a novel strategy for
      improving chemotherapy.

PMID- 25398769
TI  - To block, or not to block in advanced cirrhosis and ascites: that is the
      question.

PMID- 25398770
TI  - Association between antiviral treatment and extrahepatic outcomes in patients
      with hepatitis C virus infection.
AB  - OBJECTIVE: To elucidate the association between antiviral therapy and
      extrahepatic outcomes in individuals infected with HCV. METHODS: This nationwide
      cohort study screened 293,480 Taiwanese residents with HCV infection and excluded
      those with substantial comorbidity. A total of 12,384 eligible patients who had
      received pegylated interferon plus ribavirin between 1 October 2003 and 31
      December 2010 were enrolled in the treated cohort; they were matched 1 : 2 with
      24,768 untreated controls in the propensity score and post-diagnosis treatment
      free period. The incidences of end-stage renal disease (ESRD), acute coronary
      syndrome (ACS), ischaemic stroke and catastrophic autoimmune diseases were
      calculated after adjustment for competing mortality. RESULTS: The treated and
      untreated cohorts were followed up for a mean (+/-SD) duration of 3.3 (+/-2.5)
      and 3.2 (+/-2.4) years, respectively, until 31 December 2011. The calculated 8
      year cumulative incidences of ESRD, ACS, ischaemic stroke and autoimmune
      catastrophes between treated and untreated patients were 0.15% vs. 1.32%
      (p<0.001), 2.21% vs. 2.96% (p=0.027), 1.31% vs. 1.76% (p=0.001) and 0.57% vs.
      0.49% (p=0.816), respectively. Multivariate-adjusted Cox regression revealed that
      antiviral treatment was associated with lower risks of ESRD (HR 0.15; 95% CI 0.07
      to 0.31; p<0.001), ACS (HR 0.77; 95% CI 0.62 to 0.97; p=0.026) and ischaemic
      stroke (HR 0.62; 95% CI 0.46 to 0.83; p=0.001), but unrelated to autoimmune
      catastrophes. These favourable associations were invalid in incompletely treated
      patients with duration <16 weeks. CONCLUSIONS: Antiviral treatment for HCV is
      associated with improved renal and circulatory outcomes, but unrelated to
      catastrophic autoimmune diseases.

PMID- 25398771
TI  - Virtual portal pressure gradient from anatomic CT angiography.

PMID- 25398772
TI  - STK33 promotes hepatocellular carcinoma through binding to c-Myc.
AB  - OBJECTIVE: STK33 has been reported to play an important role in cancer cell
      proliferation. We investigated the role of STK33 in hepatocellular carcinoma
      (HCC) and its underlying mechanisms. DESIGN: 251 patients with HCC were analysed
      for association between STK33 expression and clinical stage and survival rate.
      Tamoxifen (TAM)-inducible, hepatocyte-specific STK33 transgenic and knockout mice
      models were used to study the role of STK33 in liver tumorigenesis. HCC cell
      lines were used to study the role of STK33 in cell proliferation in vitro and in
      vivo. RESULTS: STK33 expression was found to be frequently upregulated in
      patients with HCC. Significant associations were found between increased
      expression of STK33 and advanced HCC staging and shorter disease-free survival of
      patients. Overexpression of STK33 increased HCC cell proliferation both in vitro
      and in vivo, whereas suppression of STK33 inhibited this effect. Using a TAM
      inducible, hepatocyte-specific STK33 transgenic mouse model, we found that
      overexpression of STK33 resulted in increased hepatocyte proliferation, leading
      to tumour cell burst. Using a TAM-inducible, hepatocyte-specific STK33 knockout
      mouse model, we found that, when subjected to the diethylnitrosamine (DEN) liver
      cancer bioassay, STK33KO(flox/flox, Alb-ERT2-Cre) mice exhibited a markedly lower
      incidence of tumour formation compared with control mice. The underlying
      mechanism may be that STK33 binds directly to c-Myc and increases its
      transcriptional activity. In particular, the C-terminus of STK33 blocks STK33/c
      Myc association, downregulates HCC cell proliferation, and reduces DEN-induced
      liver tumour cell number and tumour size. CONCLUSIONS: STK33 plays an essential
      role in hepatocellular proliferation and liver tumorigenesis. The C-terminus of
      STK33 could be a potential therapeutic target in the treatment of patients with
      STK33-overexpressed HCC.

PMID- 25398773
TI  - Dyspepsia and weight loss in a 47-year-old man.

PMID- 25398774
TI  - Simple subgroup approximations to optimal treatment regimes from randomized
      clinical trial data.
AB  - We consider the use of randomized clinical trial (RCT) data to identify simple
      treatment regimes based on some subset of the covariate space, A. The optimal
      subset, A, is selected by maximizing the expected outcome under a treat-if-in-A
      regime, and is restricted to be a simple, as it is desirable that treatment
      decisions be made with only a limited amount of patient information required. We
      consider a two-stage procedure. In stage 1, non-parametric regression is used to
      estimate treatment effects for each subject, and in stage 2 these treatment
      effect estimates are used to systematically evaluate many subgroups of a simple,
      prespecified form to identify A. The proposed methods were found to perform
      favorably compared with two existing methods in simulations, and were applied to
      prehypertension data from an RCT.

PMID- 25398775
TI  - Standardized uptake value differences between primary and metastatic lesions in
      18F-FDG PET/CT of patients with lung cancer.
AB  - BACKGROUND: FDG-PET/CT is a robust tool for staging of lung cancer, but the
      differences in FDG uptake between primary and metastatic lesions have not yet
      been well described. PURPOSE: To define the potential range of standardized
      uptake value (SUV) differences between primary and metastatic lesions in lung
      cancer patients and to identify the factors responsible for these differences.
      MATERIAL AND METHODS: FDG-PET/CT images of 75 lung cancers with 296 metastases
      were analyzed retrospectively. Histological types, primary locations, and
      metastatic sites were recorded. The average and maximum SUV (SUVavg, SUVmax) of
      each primary tumor and metastasis were measured, and the ratio of metastatic SUVs
      to primary SUVs (M/Pavg, M/Pmax), its difference from 100% (diff-M/Pavg, diff
      M/Pmax), the ratio of ROI area of metastatic to primary lesions (ROI-M/P), and
      its difference from 100% (diff-ROI-M/P) were calculated. RESULTS: M/Pavg was in
      the range of 35.9-224.6% (mean +/- SD: 97.9% +/- 35.9%), while M/Pmax was in the
      range of 24.8-286.7% (98.1% +/- 45.3%). Furthermore, values were in the range of
      50-200% for M/Pavg in 280/296 lesions (94.6%) and for M/Pmax in 255/296 lesions
      (86.1%). M/Pavg and M/Pmax showed significant linear correlations with ROI-M/P (r
      = 0.62, 0.64, respectively). Multivariate analysis showed that diff-ROI-M/P had
      the greatest effect on diff-M/Pavg and diff-M/Pmax. CONCLUSION: The SUVs of most
      metastatic lesions ranged from half to double those of primaries in lung cancer
      patients. When the SUV of a suspected metastasis is beyond the range of half to
      double that of the primary lung cancer, other non-metastatic lesions should be
      considered, while taking ROI size into account.

PMID- 25398776
TI  - Impact of dual-energy CT prior to radioembolization (RE).
AB  - BACKGROUND: Depiction of the exact arterial liver anatomy as well as identifying
      potential extrahepatic non-target vessels is crucial for a successful preparation
      of radioembolization (RE). PURPOSE: To compare the diagnostic impact of dual
      energy computed tomography (DECT) to digital subtraction angiography prior to RE.
      MATERIAL AND METHODS: DECT was applied in 46 patients with hepatocellular
      carcinoma (HCC) prior to RE. Eighty kV DE as well as reconstructed 120 kV
      equivalent DE datasets were evaluated in comparison to correlating digital
      subtraction angiography (DSA) datasets. Two radiologists evaluated in consensus
      the delineation of liver arteries and extrahepatic non-target vessels utilizing a
      4-point scale (4 = excellent delineation; 1 = non-diagnostic). In addition, the
      arterial vascularization of liver segment IV was evaluated and classified: signal
      to-noise ratio (SNR) and contrast-to-noise ratio (CNR; liver arteries to adjacent
      liver tissue) were obtained via ROI analysis. RESULTS: Both imaging techniques
      (DECT, DSA) enabled high-quality assessment of all analyzed liver arteries. Out
      of the two CT datasets, 80 kVp-DE datasets offered superior delineation of the
      right gastric artery (3.5 +/- 0.7 vs. 2.5 +/- 0.5), the vascularization of
      segment IV (3.9 +/- 0.2 vs. 3.3 +/- 0.5) as well as potential extrahepatic non
      target vessels (3.9 +/- 0.1 vs. 3.3 +/- 0.5). In accordance to the results of the
      qualitative analysis, 80 kVp-DE datasets also yielded higher SNR (34.84 vs.
      29.31) and CNR (28.29 vs. 21.8) values in comparison to the 120 kVp datasets.
      CONCLUSION: Eighty kVp DECT enables a significantly better assessment of the
      arteries of the upper abdomen for therapy planning in comparison to correlating
      120 kVp datasets. This may allow for identification of potential extrahepatic non
      target vessels and assessment of target volume for therapy planning prior to DSA.

PMID- 25398777
TI  - Response to: 'Reliability of National Neonatal Audit Project's retinopathy of
      prematurity screening data' by Finer and colleagues.

PMID- 25398778
TI  - Reliability of National Neonatal Audit Project's retinopathy of prematurity
      screening data.

PMID- 25398779
TI  - Ebola: controlling the nightmare.

PMID- 25398782
TI  - Diversity and variability of NOD-like receptors in fungi.
AB  - Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are
      intracellular receptors that control innate immunity and other biotic
      interactions in animals and plants. NLRs have been characterized in plant and
      animal lineages, but in fungi, this gene family has not been systematically
      described. There is however previous indications of the involvement of NLR-like
      genes in nonself recognition and programmed cell death in fungi. We have analyzed
      198 fungal genomes for the presence of NLRs and have annotated a total of 5,616
      NLR candidates. We describe their phylogenetic distribution, domain organization,
      and evolution. Fungal NLRs are characterized by a great diversity of domain
      organizations, suggesting frequently occurring combinatorial assortments of
      different effector, NOD and repeat domains. The repeat domains are of the WD,
      ANK, and TPR type; no LRR motifs were found. As previously documented for WD
      repeat domains of fungal NLRs, TPR, and ANK repeats evolve under positive
      selection and show highly conserved repeats and repeat length polymorphism,
      suggesting the possibility of concerted evolution of these repeats. We identify
      novel effector domains not previously found associated with NLRs, whereas others
      are related to effector domains of plant or animals NLRs. In particular, we show
      that the HET domain found in fungal NLRs may be related to Toll/interleukin-1
      receptor domains found in animal and plant immune receptors. This description of
      fungal NLR repertoires reveals both similarities and differences with plant and
      animals NLR collections, highlights the importance of domain reassortment and
      repeat evolution and provides a novel entry point to explore the evolution of
      NLRs in eukaryotes. 

PMID- 25398783
TI  - Extensive copy number variations in admixed Indian population of African
      ancestry: potential involvement in adaptation.
AB  - Admixture mapping has been enormously resourceful in identifying genetic
      variations linked to phenotypes, adaptation, and diseases. In this study through
      analysis of copy number variable regions (CNVRs), we report extensive
      restructuring in the genomes of the recently admixed African-Indian population
      (OG-W-IP) that inhabits a highly saline environment in Western India. The study
      included subjects from OG-W-IP (OG), five different Indian and three HapMap
      populations that were genotyped using Affymetrix version 6.0 arrays. Copy number
      variations (CNVs) detected using Birdsuite were used to define CNVRs. Population
      structure with respect to CNVRs was delineated using random forest approach. OG
      genomes have a surprising excess of CNVs in comparison to other studied
      populations. Individual ancestry proportions computed using STRUCTURE also
      reveals a unique genetic component in OGs. Population structure analysis with CNV
      genotypes indicates OG to be distant from both the African and Indian ancestral
      populations. Interestingly, it shows genetic proximity with respect to CNVs to
      only one Indian population IE-W-LP4, which also happens to reside in the same
      geographical region. We also observe a significant enrichment of molecular
      processes related to ion binding and receptor activity in genes encompassing OG
      specific CNVRs. Our results suggest that retention of CNVRs from ancestral
      natives and de novo acquisition of CNVRs could accelerate the process of
      adaptation especially in an extreme environment. Additionally, this population
      would be enormously useful for dissecting genes and delineating the involvement
      of CNVs in salt adaptation. 

PMID- 25398785
TI  - Successful delivery of RRT in Ebola virus disease.
AB  - AKI has been observed in cases of Ebola virus disease. We describe the protocol
      for the first known successful delivery of RRT with subsequent renal recovery in
      a patient with Ebola virus disease treated at Emory University Hospital, in
      Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires
      meticulous attention to safety for the patient, healthcare workers, and the
      community. We specifically describe measures to decrease the risk of transmission
      of Ebola virus disease and report pilot data demonstrating no detectable Ebola
      virus genetic material in the spent RRT effluent waste. This article also
      proposes clinical practice guidelines for acute RRT in Ebola virus disease. 

PMID- 25398784
TI  - The macrophage mediates the renoprotective effects of endotoxin preconditioning.
AB  - Preconditioning is a preventative approach, whereby minimized insults generate
      protection against subsequent larger exposures to the same or even different
      insults. In immune cells, endotoxin preconditioning downregulates the
      inflammatory response and yet, preserves the ability to contain infections.
      However, the protective mechanisms of preconditioning at the tissue level in
      organs such as the kidney remain poorly understood. Here, we show that endotoxin
      preconditioning confers renal epithelial protection in various models of sepsis
      in vivo. We also tested the hypothesis that this protection results from direct
      interactions between the preconditioning dose of endotoxin and the renal tubules.
      This hypothesis is on the basis of our previous findings that endotoxin toxicity
      to nonpreconditioned renal tubules was direct and independent of immune cells.
      Notably, we found that tubular protection after preconditioning has an absolute
      requirement for CD14-expressing myeloid cells and particularly, macrophages.
      Additionally, an intact macrophage CD14-TRIF signaling pathway was essential for
      tubular protection. The preconditioned state was characterized by increased
      macrophage number and trafficking within the kidney as well as clustering of
      macrophages around S1 proximal tubules. These macrophages exhibited increased M2
      polarization and upregulation of redox and iron-handling molecules. In renal
      tubules, preconditioning prevented peroxisomal damage and abolished oxidative
      stress and injury to S2 and S3 tubules. In summary, these data suggest that
      macrophages are essential mediators of endotoxin preconditioning and required for
      renal tissue protection. Preconditioning is, therefore, an attractive model to
      investigate novel protective pathways for the prevention and treatment of sepsis.

PMID- 25398786
TI  - Endotoxin and AKI: Macrophages Protect after Preconditioning.

PMID- 25398787
TI  - Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2):
      Planted Antigens.
AB  - Glomerular planted antigens (histones, DNA, and C1q) are potential targets of
      autoimmunity in lupus nephritis (LN). However, the characterization of these
      antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular
      autoantibodies recognizing planted antigens from laser-microdissected renal
      biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined,
      levels were determined, and glomerular colocalization was investigated. Renal and
      circulating antibodies were matched, and serum levels were compared in 104
      patients with LN, 84 patients with SLE without LN, and 50 patients with
      rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti-alpha
      enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA,
      histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy
      samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit,
      and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti
      H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum,
      which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and
      glomerular levels of autoantibodies were not strictly associated. High serum
      levels of all autoantibodies detected, including anti-alpha-enolase and
      antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti-alpha-enolase
      IgG2 levels had the most remarkable increase in LN serum and represented a
      discriminating feature of LN in principal component analysis. The highest levels
      of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours
      and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody
      characterization might allow outcome prediction and targeted therapies for
      patients with nephritis. 

PMID- 25398789
TI  - A large spectrum of alpha and beta papillomaviruses are detected in human stool
      samples.
AB  - Human papillomaviruses (HPVs) have been detected in urban wastewaters,
      demonstrating that epitheliotropic viruses can find their way into sewage through
      the washing of skin and mucous membranes. Papillomavirus shedding through faeces
      is still an unexplored issue. The objective of the present study was to
      investigate the presence of HPVs in stool samples. We analysed 103 faecal
      specimens collected from hospitalized patients with diarrhoea using validated
      primers able to detect alpha, beta and gamma HPVs. PCR products underwent
      sequencing analysis and sequences were aligned to reference genomes from the
      Papillomavirus Episteme database. A total of 15 sequences were characterized from
      the faecal samples. Thirteen samples (12.6 %) were positive for nine genotypes
      belonging to the alpha and beta genera: HPV32 (LR, alpha1), HPV39 (HR, alpha7),
      HPV44 (LR, alpha10), HPV8 (beta1), HPV9, HPV23, HPV37, HPV38 and HPV120 (beta2).
      Two putative novel genotypes of the beta genus, species 1 and 2, were also
      detected. The tissue(s) of origin is unknown, since faeces can collect HPVs
      originating from or passing through the entire digestive system. To our
      knowledge, this is the first investigation on the occurrence and diversity of
      HPVs in faecal samples. Results from this study demonstrate that HPVs can find
      their way into sewage as a consequence of shedding in the faeces. This highlights
      the need for further studies aimed at understanding the prevalence of HPV in
      different water environments and the potential for waterborne transmission. 

PMID- 25398788
TI  - SREBP-1 Mediates Angiotensin II-Induced TGF-beta1 Upregulation and Glomerular
      Fibrosis.
AB  - Angiotensin II is an important mediator of CKD of diverse etiology. A common
      pathologic feature of CKD is glomerular fibrosis, a central mediator of which is
      the profibrotic cytokine TGF-beta. The mechanisms underlying the induction of TGF
      beta and matrix by angiotensin II are not completely understood. Recent studies
      showed that overexpression of the transcription factor SREBP-1 induces glomerular
      sclerosis and that angiotensin II can activate SREBP-1 in tubular cells. We thus
      studied whether SREBP-1 is activated by angiotensin II and mediates angiotensin
      II-induced profibrogenic responses in primary rat mesangial cells. Treatment of
      cells with angiotensin II induced the upregulation and activation of SREBP-1.
      Angiotensin II-induced activation of SREBP-1 required signaling through the
      angiotensin II type I receptor and activation of PI3K/Akt in addition to the
      chaperone SCAP and protease S1P. Notably, angiotensin II-induced endoplasmic
      reticulum stress was identified as a key mediator of Akt-SREBP-1 activation, and
      inhibition of endoplasmic reticulum stress or SREBP-1 prevented angiotensin II
      induced SREBP-1 binding to the TGF-beta promoter, TGF-beta upregulation, and
      downstream fibronectin upregulation. Endoplasmic reticulum stress alone, however,
      did not induce TGF-beta upregulation despite activating SREBP-1. Although not
      required for SREBP-1 activation by angiotensin II, EGF receptor signaling was
      necessary for activation of the SREBP-1 cotranscription factor Sp1, which
      provided a required second signal for TGF-beta upregulation. In vivo, endoplasmic
      reticulum stress and SREBP-1-dependent effects were induced in glomeruli of
      angiotensin II-infused mice, and administration of the SREBP inhibitor fatostatin
      prevented angiotensin II-induced TGF-beta upregulation and matrix accumulation.
      SREBP-1 and endoplasmic reticulum stress thus provide potential novel therapeutic
      targets for the treatment of CKD.

PMID- 25398790
TI  - Intrathecal overproduction of proinflammatory cytokines and chemokines in febrile
      infection-related refractory status epilepticus.

PMID- 25398791
TI  - An epiallele at cly1 affects the expression of floret closing (cleistogamy) in
      barley.
AB  - The swelling of the lodicule is responsible for floret opening in many grass
      species, allowing for pollen dispersal and cross-pollination. In barley, the
      closed floret habit (cleistogamy) is under the control of cly1, a gene that
      operates by inhibiting the development of the lodicule. In non-cleistogamous
      cultivars, cly1 mRNA is degraded by miR172-directed cleavage, allowing the
      lodicules to swell; however, in cultivars carrying the recessive allele cly1.b, a
      single-nucleotide substitution destroys the miR172 target site preventing mRNA
      cleavage. Barley cv. SV235 is cleistogamous; its cly1 coding sequence is
      identical to that of cly1.b, but its lodicules do develop, although
      insufficiently to produce a non-cleistogamous flower. In this cultivar, the
      downregulation of cly1 is unrelated to miR172-directed mRNA degradation, but
      rather is caused by an epiallele that represses transcription. Allelic
      relationships between known cly1 alleles were explored by the quantification of
      lodicule vascularization and an assessment of the response of the spike to the
      supply of exogenous auxin. The SV235 phenotype can be manipulated by a pre
      anthesis application of 2,4-d, a feature that could be of interest in the context
      of hybrid barley grain production based on cleistogamy. 

PMID- 25398793
TI  - Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification.
AB  - This article reviews epidemiology, risk factors, pathogenesis and diagnosis of
      melanoma. Data on melanoma from the majority of countries show a rapid increase
      of the incidence of this cancer, with a slowing of the rate of incidence in the
      period 1990-2000. Males are approximately 1.5-times more likely to develop
      melanoma than females, while according to other studies, the different prevalence
      in both sexes must be analyzed in relation with age: the incidence rate of
      melanoma is grater in women than men until they reach the age of 40 years,
      however, by 75 years of age, the incidence is almost 3-times as high in men
      versus women. The most important and potentially modifiable environmental risk
      factor for developing malignant melanoma is the exposure to ultraviolet (UV) rays
      because of their genotoxic effect. Artificial UV exposure may play a role in the
      development of melanoma. The most important host risk factors are the number of
      melanocytic nevi, familiar history and genetic susceptibility. A patient with a
      personal history of melanoma must be considered at greater risk for subsequent
      melanoma. Indeed approximately 1-8% of patients with prior history of melanoma
      will develop multiple primary melanomas. We herein review the dermatological
      diagnosis and classification of melanoma.

PMID- 25398792
TI  - Allelic variation, aneuploidy, and nongenetic mechanisms suppress a monogenic
      trait in yeast.
AB  - Clinically relevant features of monogenic diseases, including severity of
      symptoms and age of onset, can vary widely in response to environmental
      differences as well as to the presence of genetic modifiers affecting the trait's
      penetrance and expressivity. While a better understanding of modifier loci could
      lead to treatments for Mendelian diseases, the rarity of individuals harboring
      both a disease-causing allele and a modifying genotype hinders their study in
      human populations. We examined the genetic architecture of monogenic trait
      modifiers using a well-characterized yeast model of the human Mendelian disease
      classic galactosemia. Yeast strains with loss-of-function mutations in the yeast
      ortholog (GAL7) of the human disease gene (GALT) fail to grow in the presence of
      even small amounts of galactose due to accumulation of the same toxic
      intermediates that poison human cells. To isolate and individually genotype large
      numbers of the very rare (~0.1%) galactose-tolerant recombinant progeny from a
      cross between two gal7Delta parents, we developed a new method, called "FACS
      QTL." FACS-QTL improves upon the currently used approaches of bulk segregant
      analysis and extreme QTL mapping by requiring less genome engineering and strain
      manipulation as well as maintaining individual genotype information. Our results
      identified multiple distinct solutions by which the monogenic trait could be
      suppressed, including genetic and nongenetic mechanisms as well as frequent
      aneuploidy. Taken together, our results imply that the modifiers of monogenic
      traits are likely to be genetically complex and heterogeneous. 

PMID- 25398794
TI  - Cardiopulmonary exercise testing (CPET) as preoperative test before lung
      resection.
AB  - Lung resection is still the only potentially curative therapy for patients with
      localized non-small lung cancer (NSCLC). However, the presence of cardiovascular
      comorbidities and underlying lung disease increases the risk of postoperative
      complications. Various studies have evaluated the use of different preoperative
      tests in order to identify patients with an increased risk for postoperative
      complications, associated with prolonged hospital stay and increased morbidity
      and mortality. In this topic review, we discuss the role of cardiopulmonary
      exercise testing (CPET) as one of the preoperative tests suggested for lung
      cancer patients scheduled for lung resection. We describe different types of
      exercise testing techniques and present algorithms of preoperative evaluation in
      lung cancer patients. Overall, patients with maximal oxygen consumption (VO2max)
      <10 mL/kg/min or those with VO2max <15 mL/kg/min and both postoperative FEV1 and
      DLCO<40% predicted, are at high risk for perioperative death and postoperative
      cardiopulmonary complications, and thus should be offered an alternative medical
      treatment option. 

PMID- 25398796
TI  - Organ-specific responses of total body irradiated doxycycline-inducible manganese
      superoxide dismutase Tet/Tet mice.
AB  - BACKGROUND/AIM: We evaluated doxycycline-inducible manganese superoxide dismutase
      (MnSOD(tet/tet)) mice after 9.25 Gy total-body irradiation (TBI) or 20 Gy
      thoracic irradiation. MATERIALS AND METHODS: Six-week-old MnSOD(tet/tet) or
      control C57BL/6NHsd mice on or off doxycycline (doxy) in food received 9.25 Gy
      TBI, were sacrificed at day 19 and bone marrow, brain, esophagus, heart,
      intestine, kidney, liver, lung, spleen and tongue harvested, total RNAs extracted
      and transcripts for irradiation response genes quantitated by real time
      polymerase chain reaction (RT-PCR). RESULTS: MnSOD(tet/tet) mice only survived
      with daily injections of doxy beginning 5 days after birth until weaning, at
      which time they were placed on food containing doxy. Manganese superoxide
      dismutase (MnSOD) transcript levels were reduced in all tissues except the lung.
      Adult mice survived with low MnSOD levels, but induced by doxy or TBI. Thoracic
      irradiated MnSOD(tet/tet) mice survived past day 120. CONCLUSION: MnSOD(tet/tet)
      mice should be valuable for elucidating the role of MnSOD in growth and
      irradiation response.

PMID- 25398795
TI  - Tolerated doses in zebrafish of cytochalasins and jasplakinolide for comparison
      with tolerated doses in mice in the evaluation of pre-clinical activity of
      microfilament-directed agents in tumor model systems in vivo.
AB  - BACKGROUND/AIM: Chemotherapeutic approaches involving microtubule-directed agents
      such as the vinca alkaloids and taxanes are used extensively and effectively in
      clinical cancer therapy. There is abundant evidence of critical cytoskeletal
      differences involving microfilaments between normal and neoplastic cells, and a
      variety of natural products and semi-synthetic derivatives are available to
      exploit these differences in vitro. In spite of the availability of such
      potential anti-neoplastic agents, there has yet to be an effective microfilament
      directed agent approved for clinical use. Cytochalasins are mycogenic toxins
      derived from a variety of fungal sources that have shown promising in vitro
      efficacy in disrupting microfilaments and producing remarkable cell enlargement
      and multi-nucleation in cancer cells without producing enlargement and multi
      nucleation in normal blood cells. Jasplakinolide is a sponge toxin that
      stabilizes and rigidifies microfilaments. Insufficient in vivo data has been
      acquired to determine whether any of the microfilament-directed agents have
      valuable preferential anticancer activity in pre-clinical tumor model systems.
      This is partly because the limited availability of these agents precludes their
      initial use in large-scale mammalian pre-clinical studies. Therefore, the present
      study sought to determine the tolerated in vivo doses of cytochalasins and
      jasplakinolide in zebrafish (Danio rerio), a well-studied fish cancer model that
      is 1.5% the size of mice. We also determined the tolerated levels of a variety of
      clinically active anti-neoplastic agents in zebrafish for comparison with
      tolerated murine doses as a means to allow comparison of toxicities in zebrafish
      expressed as MUM concentrations with toxicities in mice expressed in mg/kg.
      MATERIALS AND METHODS: Tolerated doses in zebrafish with various cytochalasins or
      jasplakinolide were determined by adding the solubilized test agent to water in
      which the fish were maintained for 24 h, then restored to their normal tanks and
      monitored for a total of 96 h. RESULTS: Cytochalasin D at 0.2 MUM gave an
      approximate LD50 in zebrafish, while cytochalasin B was fully-tolerated at 5 MUM,
      and gave an LD50 of 10 MUM. 21,22-dihydrocytochalasin B was fully-tolerated at 10
      MUM. Cytochalasin C was tolerated fully at 1 MUM, ten-fold higher than the level
      for cytochalasin D that was tolerated. Jasplakinolide at 0.5 MUM did not exhibit
      any apparent acute toxicity or affect fish behavior for four days, but delayed
      toxicity was evident at days 4 and 6 when the fish died. Further, the addition of
      5 MUM glutathione (GSH) at the time of treatment substantially decreased the
      toxicity of 10 MUM cytochalasin B, a level of cytochalasin B that not otherwise
      tolerated in vivo. Such observations were likely due to GSH-mediated alkylation
      of C-20 in cytochalasin B, thereby reducing the rate of oxidation to the highly
      toxic congener, cytochalasin A, and reacting with any cytochalazin A formed. The
      protective effects of GSH are further supported by its ability to react with
      alpha, beta-unsaturated ketone moieties, as is found in cytochalasin A. GSH at
      0.8 uM was able to reduce the toxicity of 0.8 MUM cytochalasin D, but it took 20
      MUM GSH to fully protect against the toxicity of 0.8 MUM cytochalasin D.
      CONCLUSION: Pre-clinical evaluation of rare natural products such as
      microfilamented-directed agents for efficacy in vivo in tumor-bearing zebrafish
      is a feasible prospect. Dose-limiting toxicities in zebrafish expressed as MUM
      concentrations in water can be used to estimate in vivo toxicities in mice
      expressed as mg/kg.

PMID- 25398797
TI  - In vivo absorption of didanosine formulated in pellets composed of chitosan
      microspheres.
AB  - The in vivo absorption of didanosine was studied, focusing on the performance of
      a novel pharmaceutical formulation for didanosine, composed of chitosan granules
      containing didanosine incorporated in chitosan microspheres. This novel
      formulation is aimed at oral administration in AIDS therapy. The experimental
      results in male adult dogs showed controlled delivery of didanosine along 36 h,
      with a 2-fold increase in the absorption time of didanosine compared to the
      commercial granules, gastro-resistant didanosine and tablets. The higher
      absorption is due to adhesion to the intestinal membrane, improving absorption
      through increase of residence time, permeation and release. Furthermore, the
      novel formulation facilitates handling and deglutition, especially in the elderly
      and children, as well as enhances the taste and reduces the frequency of doses
      and collateral effects associated with a high concentration of the buffer agents
      usually used in other formulations. 

PMID- 25398798
TI  - CAG-repeats in the androgen receptor gene relate with plasma androgen levels in
      the Bouvier Des Flandres.
AB  - BACKGROUND: The Bouvier des Flandres (BdF) dog is predisposed to develop prostate
      carcinoma (PCA). In humans, ethnic groups with higher prevalence of PCA have
      higher serum androgens concentrations and shorter polyglutamine (CAG) repeat
      lengths in the androgen receptor (AR) gene. In dogs, shorter CAG-I lengths are
      associated with increased PCA risk. OBJECTIVE: To compare serum androgens
      concentrations in the BdF with other breeds and to determine whether CAG repeats
      length and plasma androgens concentrations are correlated. MATERIALS AND METHODS:
      Androgens were measured in 46 BdF and in 53 other dog breed. Length of CAG-I and
      CAG-III repeats were measured in 41 BdF and correlated with androgen levels.
      RESULTS: In the BdF group shorter CAG-I and longer CAG-III repeat lengths were
      associated with lower androgen concentrations. CONCLUSION: As the shorter CAG-I
      repeat is associated with an increased PCA risk, higher androgen concentrations
      may protect against the development and progression of PCA.

PMID- 25398799
TI  - Effect of melatonin on human nighttime endotoxaemia: randomized, double-blinded,
      cross-over study.
AB  - BACKGROUND: Endotoxaemia is widely used as an experimental model to study sepsis
      under controlled conditions. Nighttime endotoxaemia induces a more pronounced
      inflammatory stress response compared to daytime. Previously, we have shown that
      melatonin has antioxidative and anti-inflammatory effects in inflammatory
      response to daytime endotoxaemia. Herein, we examined the effect of melatonin in
      response to human nighttime endotoxaemia. PATIENTS AND METHODS: Twelve healthy
      male volunteers were enrolled in a randomized, placebo-controlled, double-blinded
      cross-over trial. Subjects were induced by lipopolysaccharide (LPS) endotoxin 0.3
      ng/kg body weight intravenously at 24:00. One hour prior to induction of
      endotoxaemia, an 8-h infusion of melatonin 100 mg or placebo was initiated. Blood
      samples were drawn before and 2, 4, 6 and 8 h after induction of endotoxaemia and
      plasma was tested for pro-inflammatory markers (tumor necrosis factor alpha, TNF
      alpha, interleukin-1beta, IL-1beta, interleukin-1, IL-6, and YKL-40), anti
      inflammatory markers (interleukin-1 receptor antagonist, IL-1Ra, interleukin-10,
      IL-10, soluble tumor necrosis factor receptors I and II, sTNF-RI and sTNF-RII),
      marker for oxidative damage (malondialdehyde (MDA)) and antioxidative enzyme
      (ascorbic acid (AA) and dehydroascorbic acid (DHA)). RESULTS: Compared to
      placebo, melatonin did not reduce plasma levels of any of pro- and anti
      inflammatory markers and it also failed to influence levels of AA, DHA and MDA.
      CONCLUSION: Melatonin has no beneficial effect on inflammation and oxidative
      damage induced by nighttime endotoxaemia in contrast to daytime endotoxaemia.

PMID- 25398800
TI  - Systemic host response following skin burn injury in rats: cytotoxicity and
      genotoxicity evaluation.
AB  - AIM: The aim of the present study was to investigate whether skin burn injury
      (BI) can induce cellular changes in skeletal muscle, liver, kidney and blood by
      means of DNA damage and cytotoxicity. MATERIALS AND METHODS: Thirty male Wistar
      rats were distributed into two groups: control (C) and submitted to scald burn
      (SB), subdivided into three subgroups: 1, 4 or 14 days post-injury. The
      gastrocnemius muscle and liver were dissected for histopathological evaluation
      and the single-cell gel (comet) assay was used to investigate damage in skeletal
      muscle, liver, kidney and blood cells. RESULTS: Histopathological analysis of the
      muscle in the SB group revealed congested vessels containing inflammatory cells
      for all periods evaluated post-injury. In liver, the one day post-injury SB group
      showed sinusoidal congestion, while that of 14 days post-injury exhibited an
      increased number of Kupffer cells. CONCLUSION: Despite the histophatological
      evidence, none of the groups showed any signs of genotoxicity in these target
      tissues.

PMID- 25398801
TI  - Efflux pump inhibiting properties of racemic phenothiazine derivatives and their
      enantiomers on the bacterial AcrAB-TolC system.
AB  - BACKGROUND/AIM: Bacterial resistance to antibiotics has become a serious problem
      in antibacterial chemotherapy and resistance of bacteria to chemically-unrelated
      anti-microbial agents can be associated with the over-expression of efflux pumps.
      The simultaneous therapy with efflux pump inhibitors (EPIs) could be a solution
      to improve the effectiveness of antibiotics. The response of an organism to an
      EPI often depends on how that molecule fits a particular site of a protein.
      Because enantiomers of a given compound rotate plane-polarized light in a
      solution by the same angle but in opposite directions, the rational drug design
      should take the chirality into account if there is a difference between the
      racemic compound and its enantiomers. MATERIALS AND METHODS: The main goal of the
      present study was to elucidate the role of chirality of N-hydroxyalkyl-2
      aminophenothiazines as effective EPIs by an automated method that uses the
      general efflux pump substrate ethidium bromide (EB) for the assessment of AcrAB
      TolC system of wild-type Escherichia coli K-12 AG100. It has been shown that the
      most active EPIs among the N-hydroxyalkyl-2-aminophenothiazines were the
      compounds rac-3i, (+)-3i, and (-)-3i by modulating the AcrAB-TolC efflux pump.
      CONCLUSION: Comparison of effects of enantiomeric pairs revealed that their
      activities were similar to that of racemic derivatives. Moreover, there was no
      significant difference between the racemic compounds and their enantiomers
      related to their antibacterial and efflux pump inhibiting effects.

PMID- 25398802
TI  - A novel role of CYP2E1 in human megakaryocyte development.
AB  - Cytochrome P450 2E1 (CYP2E1) has active roles in bioconversion and
      biotransformation in humans. Although predominantly present in hepatocytes,
      CYP2E1 has also been found in hematopoietic stem cells and subtypes of acute
      myeloid leukemia with unknown clinical significance except for the metabolism of
      anti-fungal drugs. In the present study, we demonstrated a novel role of CYP2E1
      inducing megakaryocyte development in human hematopoietic stem cells and leukemia
      bipotent K562 cells. CYP2E1 was induced by phorbol-12-myristate-13-acetate in
      dose-dependent manner in K562 cells as well as in hematopoietic stem cells by
      thrombopoietin, and ingenol 3,20-dibenzoate (IDB), respectively. Overexpression
      of CYP2E1 was positively correlated with megakaryocytes and in megakaryocyte
      maturation. In addition, plasmid-driven expression of CYP2E1 in K562 cells led to
      morphological transformation of leukemic blasts to pro- and mature
      megakaryocytes. In contrast, knockout of CYP2E1 by specific interfering RNA
      diverted these cells to erythroid differentiation. Finally, treatment of K562
      cells by a free radical scavenger, N-acetyl L-lysine significantly inhibited
      CYP2E1 and megakaryocyte differentiation. In summary, our data demonstrated that
      activation of CYP2E1 and reactive oxygen species signaling promotes megakaryocyte
      development. 

PMID- 25398803
TI  - Analysis of gingival pocket microflora and biochemical blood parameters in dogs
      suffering from periodontal disease.
AB  - BACKGROUND/AIM: Periodontal diseases in dogs are caused by bacteria colonising
      the oral cavity. The presence of plaque comprising accumulations of aerobic and
      anaerobic bacteria leads to the development of periodontitis. Due to the fact
      that in a large percentage of cases periodontal diseases remain undiagnosed, and
      consequently untreated, they tend to acquire a chronic character, lead to
      bacteraemia and negatively impact the health of internal organs. The aim of the
      present study was to perform a qualitative microbiological analysis of gingival
      pockets and determine the correlations between selected morphological and
      biochemical blood parameters and the extent periodontal diseases. PATIENTS AND
      METHODS: Twenty-one dogs treated for periodontal diseases were qualified for the
      study and subsequently divided into two groups: with 3rd and 4th stage of
      periodontal disease. Swabs from the patients' gingival pockets were taken for
      bacteriological testing. Blood was tested for parameters including erythrocyte
      count, haemoglobin concentration, haematocrit values and leukocyte count. Blood
      serum was analyzed with respect to the concentrations of alanine transaminase
      (ALT), aspartate transaminase (AspAT/AST) and urea. RESULTS: The microbiological
      analysis of gingival pockets indicated the presence of numerous pathogens with a
      growth tendency in bacterial cultures observed in dogs with advanced-stage
      periodontal disease. The concentration of biochemical blood markers was
      significantly higher in dogs with 4th stage of periodontal disease, to compared
      to the 3rd-stage group. Morphological parameters were not significantly different
      with the exception of haemoglobin concentration, which was lower in dogs with 4th
      stage disease. In both groups, elevated leukocyte counts were observed.
      CONCLUSION: By conducting a detailed microbiological examination, it is possible
      to provide a better prognosis, plan adequate treatment and monitor dogs treated
      for peridontopathy.

PMID- 25398804
TI  - Quantum dots-bevacizumab complexes for in vivo imaging of tumors.
AB  - BACKGROUND/AIM: The basic role of vascular endothelial growth factor (VEGF) in
      cancer is underscored by the approval of bevacizumab for first-line treatment of
      cancer patients. Recent anticancer therapeutics based on active tumor targeting
      by conjugating tumor-specific antibodies has become of great interest in
      oncology. Current progress in nanomedicine has exploited the possibility of
      designing tumor-targeted nanocarriers able to deliver specific molecule payloads
      in a selective manner to improve the efficacy and safety of cancer imaging and
      therapy. We herein aimed to determine the targeting ability of bevacizumab
      conjugated quantum dots (QDs) in vitro and in vivo. MATERIALS AND METHODS: We
      used QDs labeled with bevacizumab, in various in vitro experiments using cell
      lines derived from colorectal cancer (CRC) and breast cancer (BC). For a
      competition study of QD-bevacizumab complex and bevacizumab, the cells were pre
      treated with bevacizumab (100 nmol/L) for 24 h before exposure to the QD
      bevacizumab complex. The breast cancer cells (MDA-MB-231) were injected to 9 nude
      mice to make the xenograft tumor model. The QD-bevacizumab complex was injected
      into the tumor model and fluorescence measurements were performed at 1, 12, and
      24 h post-injection. RESULTS: Immunocytochemical data confirmed strong and
      specific binding of the QD-bevacizumab complex to the cell lines. The cells pre
      treated with an excess of bevacizumab showed absence of QD binding. The in vivo
      fluorescence image disclosed that there was an increased signal of tumor after
      the injection of QDs. Ex vivo analysis showed 3.1 +/- 0.8%, 28.6 +/- 5.4% and
      30.8 +/- 4.2% injected dose/g accumulated in the tumors at 1, 12 and 24 h
      respectively. Tumor uptake was significantly decreased in the animals pretreated
      with excess of bevacizumab (p=0.001). CONCLUSION: In conclusion, we could
      successfully detect the VEGF-expressing tumors using QDs-bevacizumab nanoprobes
      in vitro and in vivo, opening new perspectives for VEGF-targeted non-invasive
      imaging in clinical practice.

PMID- 25398805
TI  - Sex hormones differentially modulate STAT3-dependent antioxidant responses during
      oxidative stress in renal proximal tubule cells.
AB  - BACKGROUND/AIM: Gender-associated dimorphism in renal oxidative stress may be
      related to the protective effects of estrogens or the adverse effects of
      testosterone. Signal transducer and activator of transcription-3 (STAT3)
      dependent transcription is vital in renal antioxidant responses, which may be
      differentially regulated by sex hormones. MATERIALS AND METHODS: Renal proximal
      tubule cells were treated with 400 MUM H2O2 in the presence or absence of 100 nM
      dihydrotestosterone (DHT), 100 nM 17beta-estradiol (E2) or dominant-negative
      STAT3 (dnSTAT3). Production of reactive oxygen species (ROS),
      phosphorylation/transcriptional activation of STAT3 and promoter activity of the
      STAT3-regulated antioxidant gene (MnSOD) were determined. RESULTS: After
      treatment with H2O2, DHT decreased tyrosine phosphorylation/transcriptional
      activity of STAT3 and promoter activity of MnSOD while E2 increased them.
      Consequently, DHT augmented while E2 attenuated ROS production. Effects of
      dnSTAT3 were similar to DHT. CONCLUSION: Sex hormones may influence renal
      oxidative stress through differential regulation of STAT3-dependent antioxidant
      responses.

PMID- 25398806
TI  - Healing effects and superoxide dismutase activity of diode/Ga-As lasers in a
      rabbit model of osteoarthritis.
AB  - BACKGROUND/AIM: Osteoarthritis is a major cause of pain and disability in joints.
      The present study investigated the effects of differences of wavelengths and
      continuous versus pulsed delivery modes of low-level laser therapy (LLT) in a
      rabbit model of osteoarthritis. Comparison of the healing effects and superoxide
      dismutase (SOD) activity between therapy using diode and Ga-As lasers was our
      primary interest. MATERIALS AND METHODS: Simple continuous wave (808-nm diode)
      and super-pulsed wave (904-nm Ga-As) lasers were used. Osteoarthritis was induced
      by injecting hydrogen peroxide into the articular spaces of the right stifle in
      rabbits. The rabbits were randomly assigned to four groups: normal control
      without osteoarthritis induction (G1), osteoarthritis-induction group without
      treatment (G2), osteoarthritis induction with diode irradiation (G3), and
      osteoarthritis induction with Ga-As irradiation (G4). Laser irradiation was
      applied transcutaneously for 5 min every day for over four weeks, starting the
      first day after confirmation of induction of osteoarthritis. The induction of
      osteoarthritis and effects of LLT were evaluated by biochemistry, computed
      tomography, and histological analyses. RESULTS: The SOD activity in G3 and G4
      rabbits at two and four weeks after laser irradiation was significantly higher
      than that of G1 animals (p<0.05). However, there was no significant difference
      between G3 and G4 animals. Moreover, there were significant differences at two
      and four weeks between the control and osteoarthritis-induction groups, but no
      significant difference between G3 and G4 in the computed tomographic analyses and
      histological findings. CONCLUSION: These results indicate that diode and Ga-As
      lasers are similarly effective in healing and inducing SOD activity for LLT
      applications in a rabbit model of OA.

PMID- 25398807
TI  - Comparison of the genomic sequence of the microminipig, a novel breed of swine,
      with the genomic database for conventional pig.
AB  - The microminipig, which weighs less than 10 kg at an early stage of maturity, has
      been reported as a potential experimental model animal. Its extremely small size
      and other distinct characteristics suggest the possibility of a number of
      differences between the genome of the microminipig and that of conventional pigs.
      In this study, we analyzed the genomes of two healthy microminipigs using a next
      generation sequencer SOLiDTM system. We then compared the obtained genomic
      sequences with a genomic database for the domestic pig (Sus scrofa). The mapping
      coverage of sequenced tag from the microminipig to conventional pig genomic
      sequences was greater than 96% and we detected no clear, substantial genomic
      variance from these data. The results may indicate that the distinct
      characteristics of the microminipig derive from small-scale alterations in the
      genome, such as Single Nucleotide Polymorphisms or translational modifications,
      rather than large-scale deletion or insertion polymorphisms. Further
      investigation of the entire genomic sequence of the microminipig with methods
      enabling deeper coverage is required to elucidate the genetic basis of its
      distinct phenotypic traits. 

PMID- 25398808
TI  - Monitoring human herpesvirus-6 in patients with autologous stem cell
      transplantation.
AB  - BACKGROUND/AIM: Due to the increasing number of immunocompromised patients and
      widely used autologous stem cell transplantation procedures, clinicians have to
      face with the emergence of infectious diseases. In this setting, we mainly focus
      our interest on cytomegalovirus (CMV) testing and only in some cases on other
      herpesviruses (HHV). Herein, we present monitoring of HHV-6 virus re-activation
      and infection in patients after autologous stem cell transplantation. MATERIALS
      AND METHODS: One hundred and twenty-one blood and 2 cerebrospinal fluid specimens
      from 35 patients were tested for the presence of HHV-6 DNA. RESULTS: In 4
      patients, a positive HHV-6 signal was detected. In 1 patient, simultaneous
      detection of CMV and HHV-6 could be observed; however, a low copy number result
      during CMV testing was obtained. Delayed engraftment or other clinical signs of
      infection could not be detected in patients with a positive HHV-6 result, except
      in the case of patient 4 who had limbic encephalitis due to HHV-6 reactivation.
      CONCLUSION: Because of the possible severe manifestations of HHV-6 infection in
      immunocompromised patients, screening of HHV-6 infection or reactivation is
      recommended as part of the routine laboratory procedure.

PMID- 25398809
TI  - Regenerative medicine for the treatment of Teno-desmic injuries of the equine. A
      series of 150 horses treated with platelet-derived growth factors.
AB  - BACKGROUND/AIM: The aim of the present study was to evaluate the safety and the
      clinical outcome of platelet-rich plasma for the treatment of teno-desmic injures
      in competition horses. PATIENTS AND METHODS: From January 2009 to December 2011,
      150 sport horses suffering from teno-desmic injuries were treated with no-gelled
      platelet-concentrate. RESULTS: No horse showed any major adverse reaction as a
      result of the procedure. Full healing was obtained for 81% of the horses. Twelve
      percent had clinical improvement and only 7% a failure. Eight percent of cases of
      relapse were observed. No statistically significant correlation existed between
      clinical outcome and the area of the lesion. A statistically significant
      correlation existed between the clinical outcome and the age of the horse.
      CONCLUSION: Treatment with platelet-derived growth factors leads to the formation
      of a tendon with normal morphology and functionality, which translate in the
      resumption of the agonistic activity for the horses we treated.

PMID- 25398810
TI  - Relationship between tumor necrosis factor-alpha (TNFA) gene polymorphisms and
      cardiac sarcoidosis.
AB  - Identification of genetic predisposition to cardiac sarcoidosis could play a
      critical role in the detection of sub-clinical forms of the disease. The aim of
      this study was to investigate the possible correlations between the emergence of
      cardiac sarcoidosis and the -1.031T/C, -857C/T, -308G/A, and -238G/A Tumor
      Necrosis Factor-alpha (TNFA) polymorphisms in a well-defined Greek cohort. One
      hundred and seventy-three patients of Greek origin with sarcoidosis were
      recruited in the present study. Cardiac sarcoidosis was determined according to
      established criteria. Blood samples were collected and the TNFA polymorphisms
      were genotyped. No significant difference was noted between the patients with
      cardiac involvement and those without, concerning the -1.031T/C and -238G/A TNFA
      polymorphisms. Regarding the -857C/T polymorphism, the TT genotype and the T
      allele were found to be over-represented in patients with cardiac involvement
      (p=0.02 and 0.012, respectively). AA genotype of the -308G/A as well as the A
      allele were also found significantly more frequently in patients with cardiac
      sarcoidosis (p=0.014 and 0.012 respectively). From the investigated TNFA promoter
      polymorphisms, we were able to deduce nine main haplotypes. Haplotypes 3 and 5,
      including A nucleotide at position -308, and T nucleotide at position -857
      respectively, were significantly over-represented in the group with cardiac
      involvement. We detected an increased presence of genetic polymorphisms in the
      TNFA gene of patients with cardiac involvement. However, the role and the
      clinical application of these findings need further exploration. 

PMID- 25398811
TI  - IL6 plasma concentrations in patients with sepsis receiving SLED and antibiotics:
      a predictor for survival.
AB  - BACKGROUND: The present study evaluated interleukin-6 (IL6) as a predictor of
      mortality in patients and sepsis with acute kidney injury (AKI) receiving
      sustained low-efficiency dialysis (SLED) and antibiotic therapy. PATIENTS AND
      METHODS: Seven patients with sepsis receiving antibiotics and SLED for AKI were
      studied. Blood was obtained at baseline prior to SLED and antibiotics, during
      SLED, and then after stopping SLED. IL6 concentrations were measured using an
      enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean plasma IL6
      concentrations ranged between 700 and 900 pg/ml for the first 8 h after starting
      SLED but was significantly lower after discontinuation of SLED (200-250 pg/ml)
      (p=0.0044). Three out of seven patients survived to be discharged from the
      hospital and all three had significantly lower concentrations of IL6 during the
      first 8 h compared to those who died in the hospital (p<0.0001). CONCLUSION: The
      combination of SLED and antibiotic therapy was unable to lower the initial high
      plasma IL6 concentrations, and high initial IL6 concentrations predicted in
      hospital mortality.

PMID- 25398812
TI  - First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic
      cancer from routine clinical practice.
AB  - BACKGROUND: The combination of nab-paclitaxel and gemcitabine is a new effective
      first-line chemotherapy for patients with metastatic pancreatic cancer. This was
      demonstrated in the phase III MPACT trial. PATIENTS AND METHODS: Four patients
      with metastatic pancreatic cancer from our clinical practice received combination
      chemotherapy with nab-paclitaxel at doses from 100 to 125 mg/m(2) and gemcitabine
      at doses from 800 to 1,000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle. Two
      patients had elevated serum levels of total bilirubin, one older patient had
      significant comorbidities, another older patient had an Eastern Cooperative
      Oncology Group performance status of 2. RESULTS: Treatment was manageable.
      Patients showed clinical remission or disease stabilization. Overall, combination
      chemotherapy was well tolerated. CONCLUSION: Patients with metastatic pancreatic
      cancer that did not meet all criteria, as patients treated in the registration
      trial, were safely and effectively treated with first-line combination of nab
      paclitaxel and gemcitabine.

PMID- 25398813
TI  - Clinical and virological characteristics of rotavirus gastroenteritis and
      prevalence of strains in Tochigi, Japan.
AB  - AIM: Rotavirus infection is a serious gastrointestinal infection that is usually
      prevalent during winter months and often seen in infants and young children.
      Studies on genotypes of prevalent rotavirus strains are important for preventing
      infection, developing vaccines, and its evaluation. The purpose of this study was
      to make an investigation of a rotavirus infection in the Nasu Region of Tochigi,
      Japan and to compare findings to those of other regions. MATERIALS AND METHODS:
      We examined the clinical findings in 147 patients who attended the Department of
      Pediatrics at International University of Health and Welfare Hospital in the Nasu
      shiobara City, Tochigi Prefecture, Japan during April 1, 2008 to March 31, 2010.
      RESULTS: We analyzed the clinical findings of 37 patients with a fecal sample
      positive for rotavirus antigen. Furthermore, viral genotypes were determined
      using rotavirus-positive samples from 27 of these 37 patients. The genotypes were
      determined as G1P [8] in 5 samples, G3P [8] in 5 samples, G9P [8] in 3 samples,
      and G6P [9] in 2 samples. We were able to analyze the phylogenetic trees of these
      genotypes. CONCLUSION: Of particular note, we detected G6P [9] which were
      extremely rare in humans but common in cattle. Studies on changes in prevalent
      strains after vaccine introduction need to be conducted.

PMID- 25398814
TI  - Isolated central nervous system relapse in two patients with BCR-ABL-positive
      acute leukemia while receiving a next-generation tyrosine kinase inhibitor.
AB  - We describe two patients with break point cluster region-Abelsen (BCR-ABL)
      positive acute leukemia who had an isolated relapse in the central nervous system
      (CNS) while receiving a next-generation BCR-ABL inhibitor. The first had B-cell
      acute lymphoblastic leukemia which relapsed in the CNS while maintaining
      molecular remission in the bone marrow on nilotinib. The second patient had an
      isolated CNS myeloid blast crisis of chronic myeloid leukemia while maintaining
      complete cytogenetic remission in the bone marrow on dasatinib. Mutation analysis
      of the kinase domain revealed 35 base pair insertion (35INT) between exon 8 and 9
      in both cases. 

PMID- 25398815
TI  - Primary squamous cell carcinoma of the breast after cured bilateral breast
      cancer.
AB  - BACKGROUND: Primary squamous cell carcinoma (SCC) of the breast is a rare and
      aggressive neoplasm that constitutes approximately 0.1% of all breast carcinomas.
      Before the tumor can be classified as a true SCC of the breast, certain criteria
      need to be fulfilled. These are: i) more than 90% of the malignant cells must be
      of squamous cells origin; ii) tumor is independent from the overlying skin and
      nipple; iii) other sites of primary SCC have been excluded. CASE REPORT: We
      describe a case of pure SCC of the breast that arose 15 years after local
      radiation for a primary adenocarcinoma of the breast in a 54-year-old woman with
      history of bilateral breast cancer. The tumor was triple-negative with a high Ki
      67 index. The patient underwent adjuvant chemotherapy with docetaxel and oral
      fluorouracil. CONCLUSION: There are no specific guidelines for the treatment of
      primary SCC of the breast. Larger series are necessary to determine if different
      strategies of treatment and follow-up are necessary and if prognosis is really
      comparable to other histotypes of cancers of the breast.

PMID- 25398816
TI  - Prevalence of Stafne's bone cavity--retrospective analysis of 14,005 panoramic
      views.
AB  - AIM: Stafne's bone cavity (SBC) is a very rare defect, affecting only selected
      parts of the mandibular bone. Its etiology is unknown. On two-dimensional images,
      it appears as a narrowed cavity and might be interpreted as a space-occupying
      process inside the bone. The aim of the present study was to investigate the
      prevalence of SBC on panoramic views, and compare these results to published
      reports. MATERIALS AND METHODS: A total of 14,005 panoramic views were examined
      retrospectively with regard to the presence of SBC. All images were analyzed
      regarding typical characteristics as originally described by Stafne. RESULTS: A
      total of 11 cases fulfilled diagnostic criteria of SBC (0.08%). All patients were
      men (100%), at a mean age of 58.1 years (range=38-75 years). Eight patients
      (72.7%) had SBC on the left side, three patients on the right side (27.3%). In
      eight cases, SBC was found in the mandibular corpus (72.7%), and in three cases
      in the mandibular angle (27.3%). Correlating with published results, SBC was
      found at a relative frequency of 0.13%. CONCLUSION: SBC on panoramic views or
      other imaging modalities should alert the clinician to exclude other potential
      pathologies. In doubtful cases, surgical procedures might be necessary to verify
      the diagnosis.

PMID- 25398817
TI  - Does maternal underweight prior to conception influence pregnancy risks and
      outcome?
AB  - AIM: Data analyzing risks during pregnancy and neonatal outcome in Caucasian
      women with pre-conceptional underweight are scarce. PATIENTS AND METHODS: We
      conducted a retrospective cohort study in Northern Germany comparing pregnancy
      risks and neonatal outcomes in nulliparous women with either pre-conceptional
      underweight or normal weight. RESULTS: The data of 3,854 nulliparous women with
      either underweight (n = 243; BMI <= 18.5 kg/m(2)) or normal weight (n = 3611; BMI
      18.5-24.9 kg/m(2)) were screened. The risks for preterm birth (23.3 vs. 18.6%; p
      = 0.004) and neonatal underweight were significantly higher in women with
      underweight prior to conception (p < 0.0001). The risk for secondary caesarean
      sections was significantly lower in underweight patients. CONCLUSION: To our
      knowledge, the present retrospective cohort study constitutes the largest sub
      group analysis on delivery and maternal and neonatal outcome in pre
      conceptionally underweight mothers. There are significantly more preterm
      deliveries in underweight mothers, while maternal outcome and birth-associated
      trauma (lacerations, caesarean section) is not disadvantageously influenced by
      maternal underweight. Further investigations are required in order to specify
      nutritional deficits in underweight pregnant women and to optimize medication in
      cases where nutritional balance cannot be achieved in order to improve the
      neonatal status at birth.

PMID- 25398818
TI  - Long-term outcome of stapled transanal rectal resection (STARR) versus stapled
      hemorrhoidopexys (STH) for grade III-IV hemorrhoids: preliminary results.
AB  - Circular stapled transanal hemorrhoidopexy (STH) was first introduced by A. Longo
      for the correction of internal mucosal prolapse and obstructed defecation and in
      1998, was proposed as alternative to conventional excisional hemorrhoidectomy.
      More recently, stapled transanal rectal resection (STARR) has gradually gained
      popularity, as the Longo procedure, in the treatment of hemorrhoids. The aim of
      our study was to evaluate the usefulness of STARR as alternative to STH in
      patients with grade III (n=218, 68.1%) and IV (n=102, 31.9%) hemorrhoids. A group
      of 320 consecutive patients (median age=51 years; range=16-85) underwent STH
      (n=281) or STARR (n=39) procedure. The rate of postoperative bleeding (53.8% vs.
      74.4%, p<0.01) was significantly reduced in patients who underwent STARR
      procedure, which required a longer (45 +/- 22 vs. 26 +/- 11 min, p<0.01)
      operative time. There were no differences between groups with regard to use of
      painkillers, postoperative pain intensity, short- (three months) and long-term
      (one and three years) residual pain, soiling, incontinence and urgency. Patients
      treated with the STARR procedure had lower recurrence rate of hemorrhoids and a
      lower incidence of prolapse, both at one year (none vs. 1.4%, p=0.593 and 2.6%
      vs. 5.3%, p=0.396, respectively) and at two years (none vs. 6.8%, p=0.078 and
      none vs. 13.2%, p=0.012, respectively). The one-year (9.0 +/- 1.8 vs. 9.4 +/-
      0.7, p=0.171) and two-year (9.6 +/- 0.8 vs. 9.1 +/- 1.7, p=0.072) general
      satisfaction was similar but higher in STARR patients than in the STH group. In
      conclusion, according to our preliminary results, the STARR procedure leads to a
      lower incidence of complications and recurrences and should be considered for
      patients with grade III or IV hemorrhoids previously selected for stapled
      hemorrhoidectomy, as a promising alternative to STH.

PMID- 25398819
TI  - Total nitric oxide and inducible nitric oxide synthase in alcohol-dependent
      individuals during detoxification therapy.
AB  - BACKGROUND: The alterations of total nitric oxide (NO) (through total
      nitrite/nitrate) and inducible nitric oxide synthase (iNOS) concentrations were
      determined in a population of alcohol-dependent individuals without liver disease
      upon admission for detoxification, two weeks later and after completion of
      detoxification (4-6 weeks in total). MATERIALS AND METHODS: Thirty-eight men and
      nine women were included in the study. Endogenous nitrite and total
      nitrite/nitrate concentrations were measured colorimetrically and iNOS
      concentration was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Endogenous and total nitrite concentrations were found to be diagnostically
      equally conclusive, whereas iNOS values were not correlated with the other two
      parameters. All three parameters were significantly higher in alcohol-dependent
      individuals compared to controls at all time points. CONCLUSION: The preventive
      therapeutic use of iNOS inhibitors in alcohol-dependent individuals might avoid
      the injurious effects of chronic alcohol abuse, and should be a matter of further
      investigation.

PMID- 25398820
TI  - Use of tanning potential as a predictor for prostate cancer risk in African
      American men.
AB  - BACKGROUND/AIM: Vitamin D deficiency in African-Americans is common due to the
      high melanin content of the skin that reduces the absorption of UV radiation. To
      determine if there is a correlation between UV exposure, tanning potential and
      vitamin D with prostate cancer (PC) risk, we conducted a case-control study of
      183 African-American men aged 40 years and older residing in the Washington, DC
      area. PATIENTS AND METHODS: PC status was described as a binary variable as the
      presence or absence of cancer and the environmental factors as continuous
      variables. We used a logistic regression model describing PC as the response,
      while age, tanning potential, sunlight and vitamin D were treated as the
      predictors. RESULTS: Men aged 60 years and older had a seven-fold increased risk
      for developing PC compared to those aged 50 years and less (p<0.003). Tanning
      potential was a significant (p=0.05) risk factor for PC, while sunlight exposure
      and vitamin D were not. Tanning potential was also significant (p=0.044) when
      adjusted for vitamin D and age. However, tanning potential was only marginally
      significant when adjusted for sunlight exposure (p=0.064) CONCLUSION: The
      findings of this study indicate that tanning potential may be a predictor for PC
      risk in African-American men.

PMID- 25398821
TI  - Long-term progression-free survival in a metastatic pancreatic cancer patient
      treated with first-line nab-paclitaxel and gemcitabine.
AB  - BACKGROUND: Prognosis of patients with metastatic pancreatic cancer is dismal.
      Recently, two first-line combination chemotherapy regimens have shown a survival
      benefit over single-agent gemcitabine. PATIENTS AND METHODS: A 57-year old
      metastatic pancreatic cancer patient from our department (Eastern Cooperative
      Oncology Group performance status (ECOG PS): 0, baseline carbohydrate antigen
      (CA) 19-9 level: 2,900 U/ml) received 12 cycles of first-line chemotherapy with
      nab-paclitaxel and gemcitabine until disease progression within the pivotal
      Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT). RESULTS: Treatment
      with nab-paclitaxel and gemcitabine resulted in a partial response by Response
      Evaluation Criteria in Solid Tumors (RECIST), a rapid biochemical CA 19-9
      response, a progression-free survival of 13 months and an overall survival of 20
      months. Leukopenia grade 3 prompted dose reduction by two dose levels. Non
      hematological toxicities included alopecia, skin rash, nail changes and
      peripheral neuropathy (all grade 2 or less). CONCLUSION: First-line combination
      chemotherapy with nab-paclitaxel and gemcitabine is an effective and manageable
      treatment option for patients with metastatic pancreatic cancer with the
      potential for long-term disease control.

PMID- 25398822
TI  - Juvenile myoclonic epilepsy is not associated with the DRPLA gene in a European
      population.
AB  - BACKGROUND: Juvenile myoclonic epilepsy (JME), is an early-onset inherited
      generalized epilepsy which displays genetic heterogeneity, with at least 10 known
      loci. Another neurogenetic disease, dentato-rubro-pallido-luysian atrophy (DRPLA)
      presents three clinical phenotypes, one of which in Japanese displays many
      similarities to JME. AIM: The purpose of this study was to investigate whether
      the DRPLA gene is associated with JME in Caucasians. PATIENTS AND METHODS: The
      CAG repeat polymorphism in the DRPLA gene, which is expanded in patients with
      DRPLA, was examined with polymerase chain reaction amplification in 107
      individuals of Greek origin, including 24 patients with sporadic and 8 with
      familial JME, 25 healthy relatives and 50 healthy controls. RESULTS: The repeat
      sizes of all studied individuals were within the normal range. DISCUSSION: These
      results seem to exclude the DRPLA gene as a major candidate gene for JME in this
      European population.

PMID- 25398823
TI  - Serum ferroxidase activity in patients with multiple sclerosis: a pilot study.
AB  - Emerging evidence suggests that oxidative stress might contribute to
      demyelination and axonal damage in multiple sclerosis (MS). Ferroxidase (FeOx)
      activity of ceruloplasmin prevents the formation of free radicals from Fe(2+) by
      promoting the incorporation of this pro-oxidant ion to transferrin. The aim of
      our study was to investigate serum FeOx activity in a cohort of patients with MS
      and neurological controls. Serum FeOx activity was determined in 69 relapsing
      remitting patients with MS and in 62 patients with other inflammatory
      neurological disorders (OIND) and 52 patients with other non-inflammatory
      neurological disorders (NIND) as controls. Serum FeOx activity was lower (p<0.01)
      in MS and OIND than in NIND, without any significant differences among MS
      patients grouped according to clinical and magnetic resonance evidence of disease
      activity. A reduced serum FeOx activity, which can potentially lead to a rise in
      oxidative stress-induced biomolecular damage, seems to be a shared condition in
      inflammatory disorders of the central nervous system including MS. 

PMID- 25398824
TI  - HSV1 and 2 detection in the CSF of multiple sclerosis patients by real-time PCR.
AB  - AIM: The pathogenic role of Herpes Simplex Virus (HSV) 1 and 2 in Multiple
      Sclerosis (MS) still remains obscure. The aim of our study was the assessment of
      HSV1 and 2 DNA prevalence in the cerebrospinal fluid (CSF) of MS patients
      compared to patients with other neurological disorders (OND). MATERIALS AND
      METHODS: HSV1 and HSV2 DNA detection in the CSF of patients was performed by real
      time polymerase chain reaction (PCR). RESULTS: The genome of HSV1 was present in
      the CSF of 4.7% of MS patients (4 out of 85), while HSV2 was not detected in any
      patient. In the sub-group of OND patients, HSV1 was detected in 7.9% of patients
      (3 out of 38) and HSV2 was detected in 5.3% of patients (2 out of 38).
      CONCLUSION: Our data are in accordance with a limited number of previous reports,
      supporting a prevalence of HSV1 genome in less than 5% of MS patients.

PMID- 25398825
TI  - Comparison of obliteration materials used for revision canal wall-down
      mastoidectomy with mastoid obliteration.
AB  - AIM: To describe our surgical technique and compare the results of obliteration
      materials. PATIENTS AND METHODS: Fifty patients over a 7-year period were
      evaluated retrospectively. Out of these 50 consecutive patients, 29 had recurrent
      chronic otitis media (COM) with or without cholesteatoma and 21 patients had old
      open cavities. Efficacy of mastoid obliteration was assessed by an electronic
      chart review, otoendoscopic findings, temporal bone computerized tomography (CT)
      images, and postoperative caloric test. RESULTS: Among 50 patients, inferiorly
      based periosteal flap was used in 25 patients (50%) and anteriorly-based
      periosteal flap was used in the other 25 patients. Tympanic membrane and newly
      formed external auditory canal wall was intact in 48 patients (96%). The newly
      formed EAC provided sufficient aeration, and satisfactory aesthetic appearance.
      None of our patients complained of vertigo triggered by cold air or water. There
      was no significant difference in the caloric test results between the operated
      ear and the normal ear. No difference was observed in the caloric test between
      the bone pate and costal cartilage groups. CONCLUSION: Our results indicate that
      mastoid obliteration using autogenous bone pate or costal cartilage is helpful in
      improving the outcomes of revision canal wall-down mastoidectomy in patients with
      an old radical cavity and recurrent COM or cholesteatoma.

PMID- 25398828
TI  - REACH VA: Moving from Translation to System Implementation.
AB  - PURPOSE OF THE STUDY: Resources for Enhancing All Caregivers Health in the
      Department of Veterans Affairs (REACH VA) has been implemented in the VA system
      as a national program for caregivers. DESIGN AND METHODS: We describe the
      trajectory of REACH VA from national randomized clinical trial through
      translation to national implementation. The implementation is examined through
      the six stages of the Fixsen and Blase implementation process model: exploration
      and adoption, program installation, initial implementation, full operation,
      innovation, and sustainability. Different drivers that move the implementation
      process forward are important at each stage, including staff selection, staff
      training, consultation and coaching, staff evaluation, administrative support,
      program evaluation/fidelity, and systems interventions. RESULTS: Caregivers in
      the REACH VA 4 session intervention currently implemented in the VA had similar
      outcomes to longer REACH interventions, including Resources for Enhancing
      Alzheimer's Caregivers Health (REACH II). Caregivers experienced significant
      decreases in burden, depression, anxiety, number of troubling patient behaviors
      reported, caregiving frustrations, stress symptoms (feeling overwhelmed, feeling
      like crying, being frustrated as a result of caregiving, being lonely), and
      general stress. Effect sizes (Cohen's d) for these significant variables were
      between small and medium ranging from .24 to .46. IMPLICATIONS: The
      implementation of REACH VA provides a road map for implementation of other
      behavioral interventions in health care delivery settings. Lessons learned
      include the importance of implementing a proven, needed intervention, support
      from both leadership and clinical staff, willingness to respond to staff and
      organization needs and modify the intervention while preserving its integrity,
      and fitting the intervention into ongoing routines and practices.

PMID- 25398829
TI  - Inhibition of PI3Kbeta signaling with AZD8186 inhibits growth of PTEN-deficient
      breast and prostate tumors alone and in combination with docetaxel.
AB  - Loss of PTEN protein results in upregulation of the PI3K/AKT pathway, which
      appears dependent on the PI3Kbeta isoform. Inhibitors of PI3Kbeta have potential
      to reduce growth of tumors in which loss of PTEN drives tumor progression. We
      have developed a small-molecule inhibitor of PI3Kbeta and PI3Kdelta (AZD8186) and
      assessed its antitumor activity across a panel of cell lines. We have then
      explored the antitumor effects as single agent and in combination with docetaxel
      in triple-negative breast (TNBC) and prostate cancer models. In vitro, AZD8186
      inhibited growth of a range of cell lines. Sensitivity was associated with
      inhibition of the AKT pathway. Cells sensitive to AZD8186 (GI50 < 1 MUmol/L) are
      enriched for, but not exclusively associated with, PTEN deficiency. In vivo,
      AZD8186 inhibits PI3K pathway biomarkers in prostate and TNBC tumors. Scheduling
      treatment with AZD8186 shows antitumor activity required only intermittent
      exposure, and that increased tumor control is achieved when AZD8186 is used in
      combination with docetaxel. AZD8186 is a potent inhibitor of PI3Kbeta with
      activity against PI3Kdelta signaling, and has potential to reduce growth of
      tumors dependent on dysregulated PTEN for growth. Moreover, AZD8186 can be
      combined with docetaxel, a chemotherapy commonly used to treat advanced TBNC and
      prostate tumors. The ability to schedule AZD8186 and maintain efficacy offers
      opportunity to combine AZD8186 more effectively with other drugs.

PMID- 25398831
TI  - The combination of cannabidiol and Delta9-tetrahydrocannabinol enhances the
      anticancer effects of radiation in an orthotopic murine glioma model.
AB  - High-grade glioma is one of the most aggressive cancers in adult humans and long
      term survival rates are very low as standard treatments for glioma remain largely
      unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth
      as well as neutralize oncogenic processes such as angiogenesis. In an attempt to
      improve treatment outcome, we have investigated the effect of Delta(9)
      tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination
      with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261).
      Cannabinoids were used in two forms, pure (P) and as a botanical drug substance
      (BDS). Results demonstrated a duration- and dose-dependent reduction in cell
      viability with each cannabinoid and suggested that THC-BDS was more efficacious
      than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS. Median
      effect analysis revealed all combinations to be hyperadditive [T98G 48-hour
      combination index (CI) at FU50, 0.77-1.09]. Similarly, pretreating cells with THC
      P and CBD-P together for 4 hours before irradiation increased their
      radiosensitivity when compared with pretreating with either of the cannabinoids
      individually. The increase in radiosensitivity was associated with an increase in
      markers of autophagy and apoptosis. These in vitro results were recapitulated in
      an orthotopic murine model for glioma, which showed dramatic reductions in tumor
      volumes when both cannabinoids were used with irradiation (day 21: 5.5 +/- 2.2
      mm(3) vs. 48.7 +/- 24.9 mm(3) in the control group; P < 0.01). Taken together,
      our data highlight the possibility that these cannabinoids can prime glioma cells
      to respond better to ionizing radiation, and suggest a potential clinical benefit
      for glioma patients by using these two treatment modalities.

PMID- 25398830
TI  - Radiation protection of the gastrointestinal tract and growth inhibition of
      prostate cancer xenografts by a single compound.
AB  - Normal tissue toxicity markedly reduces the therapeutic index of genotoxic
      anticancer agents, including ionizing radiation. Countermeasures against tissue
      damage caused by radiation are limited by their potential to also protect
      malignant cells and tissues. Here, we tested a panel of signal transduction
      modifiers for selective radioprotection of normal but not tumor tissues. These
      included three inhibitors of GSK3 (LiCl, SB216763, and SB415286) and two
      inhibitors of NF-kappaB (ethyl pyruvate and RTA 408). Among these, the thiol
      reactive triterpenoid RTA 408 emerged as a robust and effective protector of
      multiple organ systems (gastrointestinal, skin, and hemopoietic) against lethal
      doses of radiation. RTA 408 preserved survival and proliferation of intestinal
      crypt cells in lethally irradiated mice while reducing apoptosis incidence in
      crypts and villi. In contrast, RTA 408 uniformly inhibited growth of established
      CWR22Rv1, LNCaP/C4-2B, PC3, and DU145 xenografts either alone or combined with
      radiation. Antitumor effects in vivo were associated with reduced proliferation
      and intratumoral apoptosis and with inhibition of NF-kappaB-dependent
      transcription in PC3 cells. Selective protection of normal tissue compartments by
      RTA 408 critically depended on tissue context and could not be replicated in
      vitro. Collectively, these data highlight the potential of RTA 408 as a
      cytoprotective agent that may be safely used in chemoradiation approaches.

PMID- 25398832
TI  - Phase II study of bendamustine, bortezomib and dexamethasone as second-line
      treatment for elderly patients with multiple myeloma: the Intergroupe Francophone
      du Myelome 2009-01 trial.

PMID- 25398833
TI  - JAK2, CALR, and MPL mutation spectrum in Japanese patients with
      myeloproliferative neoplasms.

PMID- 25398834
TI  - Lenalidomide interferes with tumor-promoting properties of nurse-like cells in
      chronic lymphocytic leukemia.
AB  - Lenalidomide is an immunomodulatory agent clinically active in chronic
      lymphocytic leukemia patients. The specific mechanism of action is still
      undefined, but includes modulation of the microenvironment. In chronic
      lymphocytic leukemia patients, nurse-like cells differentiate from CD14(+)
      mononuclear cells and protect chronic lymphocytic leukemia cells from apoptosis.
      Nurse-like cells resemble M2 macrophages with potent immunosuppressive functions.
      Here, we examined the effect of lenalidomide on the monocyte/macrophage
      population in chronic lymphocytic leukemia patients. We found that lenalidomide
      induces high actin polymerization on CD14(+) monocytes through activation of
      small GTPases, RhoA, Rac1 and Rap1 that correlated with increased adhesion and
      impaired monocyte migration in response to CCL2, CCL3 and CXCL12. We observed
      that lenalidomide increases the number of nurse-like cells that lost the ability
      to nurture chronic lymphocytic leukemia cells, acquired properties of
      phagocytosis and promoted T-cell proliferation. Gene expression signature,
      induced by lenalidomide in nurse-like cells, indicated a reduction of pivotal pro
      survival signals for chronic lymphocytic leukemia, such as CCL2, IGF1, CXCL12,
      HGF1, and supported a modulation towards M1 phenotype with high IL2 and low IL10,
      IL8 and CD163. Our data provide new insights into the mechanism of action of
      lenalidomide that mediates a pro-inflammatory switch of nurse-like cells
      affecting the protective microenvironment generated by chronic lymphocytic
      leukemia into tissues. 

PMID- 25398835
TI  - Extending the clinical and immunological phenotype of human interleukin-21
      receptor deficiency.

PMID- 25398836
TI  - Lenalidomide and dexamethasone for acute light chain-induced renal failure: a
      phase II study.
AB  - We prospectively evaluated the activity and tolerance of lenalidomide
      dexamethasone in 35 patients with acute light chain-induced renal failure. The
      lenalidomide dose was adapted to the estimated glomerular filtration rate and
      dexamethasone was given at high dose in cycle one and at low dose thereafter.
      Four patients died within the first two cycles, and five discontinued therapy
      leaving 26 patients for the per-protocol analysis. Responses were observed in
      24/35 (68.6%) patients of the intent-to-treat population. Complete response was
      noted in seven patients (20%), very good partial response in three patients
      (8.6%), partial response in 14 patients (40%), and minimal response in one
      patient (2.9%). Renal response was observed in 16 (45.7%) patients: five (14.2%)
      achieved complete, four (11.4%) partial and seven (20%) minor renal responses.
      Five of 13 patients who were dialysis dependent at baseline became dialysis
      independent. The median time to myeloma and to renal response was 28 days for
      both parameters, while the median time to best myeloma and best renal response
      was 92 and 157 days, respectively. The median estimated glomerular filtration
      rate increased significantly in patients with partial response or better from
      17.1 mL/min at baseline to 39.1 mL/min at best response (P=0.001). The median
      progression-free and overall survival was 5.5 and 21.8 months, respectively, in
      the intent-to-treat population and 12.1 and 31.4 months, respectively, in the per
      protocol group. Infections, cardiotoxicity, anemia and thrombocytopenia were the
      most frequent toxicities. In conclusion, the lenalidomide-dexamethasone regimen
      achieved rapid and substantial myeloma and renal responses. The trial was
      registered under EUDRACT number 2008-006497-15. 

PMID- 25398837
TI  - The inverse agonist DG172 triggers a PPARbeta/delta-independent myeloid lineage
      shift and promotes GM-CSF/IL-4-induced dendritic cell differentiation.
AB  - The stilbene derivative (Z)-2-(2-bromophenyl)-3-{[4-(1
      methylpiperazine)amino]phenyl}acrylonitrile (DG172) was developed as a highly
      selective inhibitory peroxisome proliferator-activated receptor (PPAR)beta/delta
      ligand. Here, we describe a novel PPARbeta/delta-independent, yet highly
      specific, effect of DG172 on the differentiation of bone marrow cells (BMCs).
      DG172 strongly augmented granulocyte-macrophage-colony-stimulating factor (GM
      CSF)-induced differentiation of primary BMCs from Ppard null mice into two
      specific populations, characterized as mature (CD11c(hi)MHCII(hi)) and immature
      (CD11c(hi)MHCII(lo)) dendritic cells (DCs). IL-4 synergized with DG172 to shift
      the differentiation from MHCII(lo) cells to mature DCs in vitro. The promotion of
      DC differentiation occurred at the expense of differentiation to granulocytic
      Gr1(+)Ly6B(+) cells. In agreement with these findings, transcriptome analyses
      showed a strong DG172-mediated repression of genes encoding neutrophilic markers
      in both differentiating wild-type and Ppard null cells, while macrophage/DC
      marker genes were up-regulated. DG172 also inhibited the expression of
      transcription factors driving granulocytic differentiation (Cebpe, Gfi1, and
      Klf5), and increased the levels of transcription factors promoting macrophage/DC
      differentiation (Irf4, Irf8, Spib, and Spic). DG172 exerted these effects only at
      an early stage of BMC differentiation induced by GM-CSF, did not affect
      macrophage-colony-stimulating factor-triggered differentiation to macrophages and
      had no detectable PPARbeta/delta-independent effect on other cell types tested.
      Structure-function analyses demonstrated that the 4-methylpiperazine moiety in
      DG172 is required for its effect on DC differentiation, but is dispensable for
      PPARbeta/delta binding. Based on these data we developed a new compound, (Z)-2-(4
      chlorophenyl)-3-[4-(4-methylpiperazine-1-yl)phenyl]acrylonitrile (DG228), which
      enhances DC differentiation in the absence of significant PPARbeta/delta binding.

PMID- 25398838
TI  - Organizational change theory: implications for health promotion practice.
AB  - Sophisticated understandings of organizational dynamics and processes of
      organizational change are crucial for the development and success of health
      promotion initiatives. Theory has a valuable contribution to make in
      understanding organizational change, for identifying influential factors that
      should be the focus of change efforts and for selecting the strategies that can
      be applied to promote change. This article reviews select organizational change
      models to identify the most pertinent insights for health promotion
      practitioners. Theoretically derived considerations for practitioners who seek to
      foster organizational change include the extent to which the initiative is
      modifiable to fit with the internal context; the amount of time that is allocated
      to truly institutionalize change; the ability of the agents of change to build
      short-term success deliberately into their implementation plan; whether or not
      the shared group experience of action for change is positive or negative and the
      degree to which agencies that are the intended recipients of change are resourced
      to focus on internal factors. In reviewing theories of organizational change, the
      article also addresses strategies for facilitating the adoption of key
      theoretical insights into the design and implementation of health promotion
      initiatives in diverse organizational settings. If nothing else, aligning health
      promotion with organizational change theory promises insights into what it is
      that health promoters do and the time that it can take to do it effectively. 

PMID- 25398839
TI  - Type 2 myocardial infarction.

PMID- 25398841
TI  - Central nervous system malignancies: what next?

PMID- 25398842
TI  - Facing the future of brain tumor clinical research.
AB  - This edition of CCR Focus provides critical reviews of several important areas in
      the field, including the application of findings from genomic investigations of
      brain tumors to improve diagnosis, clinical trial design, and ultimately
      optimizing individual patient treatment. Another article is a critical review
      provided by experts in the field that discusses the recent clinical trials using
      angiogenesis inhibitors, possible explanations for the results, and how to move
      forward. There is a concise discussion of the application of immunotherapy to
      brain tumors by key investigators in this field, reflecting the potential
      opportunities as well as the disease-specific challenges. Finally, leading
      pediatric brain tumor investigators provide an overview of the field and insights
      about the recent seminal discoveries in two pediatric brain tumors, supporting
      the paradigm that laboratory investigations lead to more precise diagnosis,
      prognosis, and ultimately better treatment. Herein, an overview of the recent
      advances and challenges in the area of clinical and translational brain tumor
      research is provided to set the stage for the contributions that follow.

PMID- 25398843
TI  - The evolving role of molecular markers in the diagnosis and management of diffuse
      glioma.
AB  - While the classification of diffuse gliomas has relied on the examination of
      morphologic features supplemented with techniques such as immunohistochemistry,
      there is an increasing recognition of substantial biologic diversity within
      morphologically defined entities. High-throughput technologies, in particular
      studies that integrate genome-wide data from diverse molecular platforms,
      increasingly identify the existence of robust and distinct glioma subtypes. While
      treatment advances and improvement of outcomes for patients with diffuse glioma
      have been modest, there may be benefit to integrate findings from biologic
      studies into clinical practice to enhance the precision of treatment for these
      diseases. Recent examples such as the identification of mutations in IDH1 and
      IDH2 as an early genetic event that is predominantly in lower-grade gliomas
      (grades 2 and 3) underscore the importance of molecular discovery leading to the
      ability to develop subclassifications with prognostic and potentially therapeutic
      implications. In contrast, glioblastoma (grade 4), the most common and aggressive
      glioma, typically arises without IDH mutation, supporting the need for different
      therapeutic approaches. Additional genomic and epigenomic signatures are
      generally nonoverlapping between IDH-mutant and IDH wild-type diffuse glioma, and
      despite comparable histopathology, IDH-mutant gliomas can be considered as
      biologically distinct from IDH wild-type gliomas. In this CCR Focus article, we
      highlight and summarize the current understanding of recent molecular findings
      and the relationships of these findings to clinical trials and clinical
      management.

PMID- 25398844
TI  - Antiangiogenic therapy for glioblastoma: current status and future prospects.
AB  - Glioblastoma is characterized by high expression levels of proangiogenic
      cytokines and microvascular proliferation, highlighting the potential value of
      treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a
      beneficial impact through multiple mechanisms of action. Ultimately, however,
      alternative proangiogenic signal transduction pathways are activated, leading to
      the development of resistance, even in tumors that initially respond. The
      identification of biomarkers or imaging parameters to predict response and to
      herald resistance is of high priority. Despite promising phase II clinical trial
      results and patient benefit in terms of clinical improvement and longer
      progression-free survival, an overall survival benefit has not been demonstrated
      in four randomized phase III trials of bevacizumab or cilengitide in newly
      diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma.
      However, future studies are warranted. Predictive markers may allow appropriate
      patient enrichment, combination with chemotherapy may ultimately prove successful
      in improving overall survival, and novel agents targeting multiple proangiogenic
      pathways may prove effective.

PMID- 25398845
TI  - Immunotherapy for primary brain tumors: no longer a matter of privilege.
AB  - Immunotherapy for cancer continues to gain both momentum and legitimacy as a
      rational mode of therapy and a vital treatment component in the emerging era of
      personalized medicine. Gliomas, and their most malignant form, glioblastoma,
      remain as a particularly devastating solid tumor for which standard treatment
      options proffer only modest efficacy and target specificity. Immunotherapy would
      seem a well-suited choice to address such deficiencies given both the modest
      inherent immunogenicity of gliomas and the strong desire for treatment
      specificity within the confines of the toxicity-averse normal brain. This review
      highlights the caveats and challenges to immunotherapy for primary brain tumors,
      as well as reviewing modalities that are currently used or are undergoing active
      investigation. Tumor immunosuppressive countermeasures, peculiarities of central
      nervous system immune access, and opportunities for rational treatment design are
      discussed.

PMID- 25398846
TI  - Molecular insights into pediatric brain tumors have the potential to transform
      therapy.
AB  - High-throughput genomic technologies have shed light on the biologic
      heterogeneity of several pediatric brain tumors. The biology of the four common
      pediatric brain tumors-namely medulloblastoma; ependymoma; high-grade glioma
      (HGG), including diffuse intrinsic pontine glioma; and low-grade glioma-is
      highlighted in this CCR Focus article. The discovery that medulloblastoma
      consists of four different subgroups, namely WNT, SHH, Group 3, and Group 4, each
      with distinct clinical and molecular features, has affected the treatment of
      children with medulloblastoma. Prospective studies have documented the efficacy
      of SMO inhibitors in a subgroup of patients with SHH medulloblastoma. Efforts are
      ongoing to develop specific therapies for each of the subgroups of
      medulloblastoma. Similar efforts are being pursued for ependymoma, HGG, and
      diffuse intrinsic pontine glioma where the disease outcome for the latter two
      tumors has not changed over the past three decades despite several prospective
      clinical trials. Developing and testing targeted therapies based on this new
      understanding remains a major challenge to the pediatric neuro-oncology
      community. The focus of this review is to summarize the rapidly evolving
      understanding of the common pediatric brain tumors based on genome-wide analysis.
      These novel insights will add impetus to translating these laboratory-based
      discoveries to newer therapies for children diagnosed with these tumors.

PMID- 25398847
TI  - PIK3CA mutational status in circulating tumor cells can change during disease
      recurrence or progression in patients with breast cancer.
AB  - PURPOSE: Molecular characterization of circulating tumor cells (CTC) is crucial
      for the investigation of molecular-targeted therapies while PIK3CA somatic
      mutations play a crucial role in therapy response. We investigated the presence
      of PIK3CA mutations in CTC and whether this is associated with clinical outcome.
      EXPERIMENTAL DESIGN: We developed and validated an ultrasensitive methodology for
      the detection of PIK3CA mutations that is based on a combination of allele
      specific, asymmetric rapid PCR and melting analysis. We analyzed PIK3CA hotspot
      mutations in: (i) a training group consisting of EpCAM-positive CTC fraction from
      37 patients with clinically confirmed metastasis, and 26 healthy female
      volunteers and 15 primary breast tumor tissues and (ii) an independent group
      consisting of EpCAM-positive CTC fraction from 57 metastatic and 118 operable
      breast cancer patients and 76 corresponding primary tumors. RESULTS: The assay
      could detect 0.05% of mutated dsDNA in the presence of 99.95% wtDNA for both
      exons (9 and 20) and was highly specific (0/26 healthy donors). PIK3CA mutations
      were identified in EpCAM-positive CTC in 20 of 57(35.1%) and in 23 of 118 (19.5%)
      patients with metastatic and operable breast cancer, and in 45 of 76(59.2%)
      corresponding FFPEs. Our data indicate that PIK3CA mutational status in CTCs can
      change during disease progression and is associated with worse survival (P =
      0.047). CONCLUSIONS: PIK3CA hotspot mutations are present at a relatively high
      frequency in CTCs and their presence is associated with worse survival in
      patients with breast cancer with metastasis. Evaluation of PIK3CA mutational
      status in CTCs is a strategy with potential clinical application.

PMID- 25398848
TI  - Calcium channel blockers and hypertension.
AB  - Effective treatment of high blood pressure (BP) represents a key strategy for
      reducing the burden of hypertension-related cardiovascular and renal diseases. In
      spite of these well-established concepts, hypertension remains poorly controlled
      worldwide. In order to improve BP control in patients with hypertension, several
      interventions have been proposed, among which (1) preferred use of more
      effective, sustained, and well-tolerated antihypertensive drug aimed to ensure
      adherence to prescribed medications and (2) extensive use of rational,
      integrated, and synergistic combination therapies, even as first-line strategy,
      aimed to achieve the recommended BP targets. Within the possible antihypertensive
      drug classes currently available for the clinical management of hypertension,
      both in monotherapy and in combination therapy, drugs inhibiting the renin
      angiotensin system and calcium channel blockers (CCBs) have demonstrated to be
      effective and safe in lowering BP levels and achieving the recommended BP targets
      with a good tolerability profile. In particular, CCBs have been one of the most
      widely used classes of antihypertensive agents in the last 20 years, based on
      their effectiveness in reducing BP levels, good tolerability, and abundant
      evidence on reducing cardiovascular and renal consequences of hypertension. This
      article provides an updated overview of the evidence supporting the use of CCBs
      based antihypertensive regimen, both in monotherapy and in combination therapies
      with different classes of antihypertensive drugs. 

PMID- 25398849
TI  - Actionable sequence data on infectious diseases in the clinical workplace.

PMID- 25398850
TI  - The Fingerprint of Rapid Eye Movement: Its Algorithmic Detection in the Sleep
      Electroencephalogram Using a Single Derivation.
AB  - The strong associations of rapid eye movement (REM) sleep with dreaming and
      memory consolidation imply the existence of REM-specific brain electrical
      activity, notwithstanding the visual similarity of the electroencephalograms
      (EEGs) in REM and wake states. Our goal was to detect REM sleep by means of
      algorithmic analysis of the EEG. We postulated that novel depth and fragmentation
      variables, defined in relation to temporal changes in the signal (recurrences),
      could be statistically combined to allow disambiguation of REM epochs. The
      cohorts studied were consecutive patients with obstructive sleep apnea (OSA)
      recruited from a sleep medicine clinic, and clinically normal participants
      selected randomly from a national database (N = 20 in each cohort). Individual
      discriminant analyses were performed, for each subject based on 4 recurrence
      biomarkers, and used to classify every 30-second epoch in the subject's overnight
      polysomnogram as REM or NotREM (wake or any non-REM sleep stage), using standard
      clinical staging as ground truth. The primary outcome variable was the accuracy
      of algorithmic REM classification. Average accuracies of 90% and 87% (initial and
      cross-validation analyses) were achieved in the OSA cohort; corresponding results
      in the normal cohort were 87% and 85%. Analysis of brain recurrence allowed
      identification of REM sleep, disambiguated from wake and all other stages, using
      only a single EEG lead, in subjects with or without OSA.

PMID- 25398852
TI  - Open fractures of the foot and ankle: an evidence-based review.
AB  - Open fractures have been associated with high rates of morbidity and mortality.
      Morbidity and mortality rates have improved with the advancements in infectious
      disease, plastic and reconstructive surgery, as well as damage control
      orthopaedics. Despite these advancements, few reports have focused on management
      of open foot and ankle fractures. This review outlines evidence-based principles
      for open fracture management and how these principles are applied to the foot and
      ankle. LEVELS OF EVIDENCE: Level V, Expert Opinion.

PMID- 25398851
TI  - Untangling dopamine-adenosine receptor-receptor assembly in experimental
      parkinsonism in rats.
AB  - Parkinson's disease (PD) is a dopaminergic-related pathology in which functioning
      of the basal ganglia is altered. It has been postulated that a direct receptor
      receptor interaction - i.e. of dopamine D2 receptor (D2R) with adenosine A2A
      receptor (A2AR) (forming D2R-A2AR oligomers) - finely regulates this brain area.
      Accordingly, elucidating whether the pathology prompts changes to these complexes
      could provide valuable information for the design of new PD therapies. Here, we
      first resolved a long-standing question concerning whether D2R-A2AR assembly
      occurs in native tissue: by means of different complementary experimental
      approaches (i.e. immunoelectron microscopy, proximity ligation assay and TR
      FRET), we unambiguously identified native D2R-A2AR oligomers in rat striatum.
      Subsequently, we determined that, under pathological conditions (i.e. in a rat PD
      model), D2R-A2AR interaction was impaired. Collectively, these results provide
      definitive evidence for alteration of native D2R-A2AR oligomers in experimental
      parkinsonism, thus conferring the rationale for appropriate oligomer-based PD
      treatments. 

PMID- 25398854
TI  - Retraction: Novel HSP90 inhibitor NVP-HSP990 targets cell-cycle regulators to
      ablate Olig 2-positive glioma tumor-initiating cells.

PMID- 25398855
TI  - A previously uncharacterized, nonphotosynthetic member of the Chromatiaceae is
      the primary CO2-fixing constituent in a self-regenerating biocathode.
AB  - Biocathode extracellular electron transfer (EET) may be exploited for
      biotechnology applications, including microbially mediated O2 reduction in
      microbial fuel cells and microbial electrosynthesis. However, biocathode
      mechanistic studies needed to improve or engineer functionality have been limited
      to a few select species that form sparse, homogeneous biofilms characterized by
      little or no growth. Attempts to cultivate isolates from biocathode environmental
      enrichments often fail due to a lack of some advantage provided by life in a
      consortium, highlighting the need to study and understand biocathode consortia in
      situ. Here, we present metagenomic and metaproteomic characterization of a
      previously described biocathode biofilm (+310 mV versus a standard hydrogen
      electrode [SHE]) enriched from seawater, reducing O2, and presumably fixing CO2
      for biomass generation. Metagenomics identified 16 distinct cluster genomes, 15
      of which could be assigned at the family or genus level and whose abundance was
      roughly divided between Alpha- and Gammaproteobacteria. A total of 644 proteins
      were identified from shotgun metaproteomics and have been deposited in the the
      ProteomeXchange with identifier PXD001045. Cluster genomes were used to assign
      the taxonomic identities of 599 proteins, with Marinobacter, Chromatiaceae, and
      Labrenzia the most represented. RubisCO and phosphoribulokinase, along with 9
      other Calvin-Benson-Bassham cycle proteins, were identified from Chromatiaceae.
      In addition, proteins similar to those predicted for iron oxidation pathways of
      known iron-oxidizing bacteria were observed for Chromatiaceae. These findings
      represent the first description of putative EET and CO2 fixation mechanisms for a
      self-regenerating, self-sustaining multispecies biocathode, providing potential
      targets for functional engineering, as well as new insights into biocathode EET
      pathways using proteomics. 

PMID- 25398856
TI  - Highly dynamic genomic loci drive the synthesis of two types of capsular or
      secreted polysaccharides within the Mycoplasma mycoides cluster.
AB  - Mycoplasmas of the Mycoplasma mycoides cluster are all ruminant pathogens.
      Mycoplasma mycoides subsp. mycoides is responsible for contagious bovine
      pleuropneumonia and is known to produce capsular polysaccharide (CPS) and
      exopolysaccharide (EPS). Previous studies have strongly suggested a role for
      Mycoplasma mycoides subsp. mycoides polysaccharides in pathogenicity. Mycoplasma
      mycoides subsp. mycoides-secreted EPS was recently characterized as a beta(1->6)
      galactofuranose homopolymer (galactan) identical to the capsular product. Here,
      we extended the characterization of secreted polysaccharides to all other members
      of the M. mycoides cluster: M. capricolum subsp. capripneumoniae, M. capricolum
      subsp. capricolum, M. leachii, and M. mycoides subsp. capri (including the LC and
      Capri serovars). Extracted EPS was characterized by nuclear magnetic resonance,
      resulting in the identification of a homopolymer of beta(1->2)-glucopyranose
      (glucan) in M. capricolum subsp. capripneumoniae and M. leachii. Monoclonal
      antibodies specific for this glucan and for the Mycoplasma mycoides subsp.
      mycoides-secreted galactan were used to detect the two polysaccharides. While M.
      mycoides subsp. capri strains of serovar LC produced only capsular galactan, no
      polysaccharide could be detected in strains of serovar Capri. All strains of M.
      capricolum subsp. capripneumoniae and M. leachii produced glucan CPS and EPS,
      whereas glucan production and localization varied among M. capricolum subsp.
      capricolum strains. Genes associated with polysaccharide synthesis and forming a
      biosynthetic pathway were predicted in all cluster members. These genes were
      organized in clusters within two loci representing genetic variability hot spots.
      Phylogenetic analysis showed that some of these genes, notably galE and glf, were
      acquired via horizontal gene transfer. These findings call for a reassessment of
      the specificity of the serological tests based on mycoplasma polysaccharides. 

PMID- 25398857
TI  - New multilocus variable-number tandem-repeat analysis tool for surveillance and
      local epidemiology of bacterial leaf blight and bacterial leaf streak of rice
      caused by Xanthomonas oryzae.
AB  - Multilocus variable-number tandem-repeat analysis (MLVA) is efficient for routine
      typing and for investigating the genetic structures of natural microbial
      populations. Two distinct pathovars of Xanthomonas oryzae can cause significant
      crop losses in tropical and temperate rice-growing countries. Bacterial leaf
      streak is caused by X. oryzae pv. oryzicola, and bacterial leaf blight is caused
      by X. oryzae pv. oryzae. For the latter, two genetic lineages have been described
      in the literature. We developed a universal MLVA typing tool both for the
      identification of the three X. oryzae genetic lineages and for epidemiological
      analyses. Sixteen candidate variable-number tandem-repeat (VNTR) loci were
      selected according to their presence and polymorphism in 10 draft or complete
      genome sequences of the three X. oryzae lineages and by VNTR sequencing of a
      subset of loci of interest in 20 strains per lineage. The MLVA-16 scheme was then
      applied to 338 strains of X. oryzae representing different pathovars and
      geographical locations. Linkage disequilibrium between MLVA loci was calculated
      by index association on different scales, and the 16 loci showed linear Mantel
      correlation with MLSA data on 56 X. oryzae strains, suggesting that they provide
      a good phylogenetic signal. Furthermore, analyses of sets of strains for
      different lineages indicated the possibility of using the scheme for deeper
      epidemiological investigation on small spatial scales. 

PMID- 25398858
TI  - Occurrence of Antimicrobial-Resistant Escherichia coli and Salmonella enterica in
      the Beef Cattle Production and Processing Continuum.
AB  - Specific concerns have been raised that third-generation cephalosporin-resistant
      (3GC(r)) Escherichia coli, trimethoprim-sulfamethoxazole-resistant (COT(r)) E.
      coli, 3GC(r) Salmonella enterica, and nalidixic acid-resistant (NAL(r)) S.
      enterica may be present in cattle production environments, persist through beef
      processing, and contaminate final products. The prevalences and concentrations of
      these organisms were determined in feces and hides (at feedlot and processing
      plant), pre-evisceration carcasses, and final carcasses from three lots of fed
      cattle (n = 184). The prevalences and concentrations were further determined for
      strip loins from 103 of the carcasses. 3GC(r) Salmonella was detected on 7.6% of
      hides during processing and was not detected on the final carcasses or strip
      loins. NAL(r) S. enterica was detected on only one hide. 3GC(r) E. coli and
      COT(r) E. coli were detected on 100.0% of hides during processing. Concentrations
      of 3GC(r) E. coli and COT(r) E. coli on hides were correlated with pre
      evisceration carcass contamination. 3GC(r) E. coli and COT(r) E. coli were each
      detected on only 0.5% of final carcasses and were not detected on strip loins.
      Five hundred and 42 isolates were screened for extraintestinal pathogenic E. coli
      (ExPEC) virulence-associated markers. Only two COT(r) E. coli isolates from hides
      were ExPEC, indicating that fed cattle products are not a significant source of
      ExPEC causing human urinary tract infections. The very low prevalences of these
      organisms on final carcasses and their absence on strip loins demonstrate that
      current sanitary dressing procedures and processing interventions are effective
      against antimicrobial-resistant bacteria. 

PMID- 25398859
TI  - Up against the wall: is yeast cell wall integrity ensured by mechanosensing in
      plasma membrane microdomains?
AB  - Yeast cell wall integrity (CWI) signaling serves as a model of the regulation of
      fungal cell wall synthesis and provides the basis for the development of
      antifungal drugs. A set of five membrane-spanning sensors (Wsc1 to Wsc3, Mid2,
      and Mtl1) detect cell surface stress and commence the signaling pathway upon
      perturbations of either the cell wall structure or the plasma membrane. We here
      summarize the latest advances in the structure/function relationship primarily of
      the Wsc1 sensor and critically review the evidence that it acts as a
      mechanosensor. The relevance and physiological significance of the information
      obtained for the function of the other CWI sensors, as well as expected future
      developments, are discussed. 

PMID- 25398860
TI  - Molecular toolbox for genetic manipulation of the stalked budding bacterium
      Hyphomonas neptunium.
AB  - The alphaproteobacterium Hyphomonas neptunium proliferates by a unique budding
      mechanism in which daughter cells emerge from the end of a stalk-like extension
      emanating from the mother cell body. Studies of this species so far have been
      hampered by the lack of a genetic system and of molecular tools allowing the
      regulated expression of target genes. Based on microarray analyses, this work
      identifies two H. neptunium promoters that are activated specifically by copper
      and zinc. Functional analyses show that they have low basal activity and a high
      dynamic range, meeting the requirements for use as a multipurpose expression
      system. To facilitate their application, the two promoters were incorporated into
      a set of integrative plasmids, featuring a choice of two different selection
      markers and various fluorescent protein genes. These constructs enable the
      straightforward generation and heavy metal-inducible synthesis of fluorescent
      protein fusions in H. neptunium, thereby opening the door to an in-depth analysis
      of polar growth and development in this species. 

PMID- 25398861
TI  - Autotransporter-based antigen display in bacterial ghosts.
AB  - Bacterial ghosts are empty cell envelopes of Gram-negative bacteria that can be
      used as vehicles for antigen delivery. Ghosts are generated by releasing the
      bacterial cytoplasmic contents through a channel in the cell envelope that is
      created by the controlled production of the bacteriophage phiX174 lysis protein
      E. While ghosts possess all the immunostimulatory surface properties of the
      original host strain, they do not pose any of the infectious threats associated
      with live vaccines. Recently, we have engineered the Escherichia coli
      autotransporter hemoglobin protease (Hbp) into a platform for the efficient
      surface display of heterologous proteins in Gram-negative bacteria, HbpD. Using
      the Mycobacterium tuberculosis vaccine target ESAT6 (early secreted antigenic
      target of 6 kDa), we have explored the application of HbpD to decorate E. coli
      and Salmonella ghosts with antigens. The use of different promoter systems
      enabled the concerted production of HbpD-ESAT6 and lysis protein E. Ghost
      formation was monitored by determining lysis efficiency based on CFU, the
      localization of a set of cellular markers, fluorescence microscopy, flow
      cytometry, and electron microscopy. Hbp-mediated surface display of ESAT6 was
      monitored using a combination of a protease accessibility assay, fluorescence
      microscopy, flow cytometry and (immuno-)electron microscopy. Here, we show that
      the concerted production of HbpD and lysis protein E in E. coli and Salmonella
      can be used to produce ghosts that efficiently display antigens on their surface.
      This system holds promise for the development of safe and cost-effective vaccines
      with optimal intrinsic adjuvant activity and exposure of heterologous antigens to
      the immune system. 

PMID- 25398862
TI  - Association of biodiversity with the rates of micropollutant biotransformations
      among full-scale wastewater treatment plant communities.
AB  - Biodiversities can differ substantially among different wastewater treatment
      plant (WWTP) communities. Whether differences in biodiversity translate into
      differences in the provision of particular ecosystem services, however, is under
      active debate. Theoretical considerations predict that WWTP communities with more
      biodiversity are more likely to contain strains that have positive effects on the
      rates of particular ecosystem functions, thus resulting in positive associations
      between those two variables. However, if WWTP communities were sufficiently
      biodiverse to nearly saturate the set of possible positive effects, then positive
      associations would not occur between biodiversity and the rates of particular
      ecosystem functions. To test these expectations, we measured the taxonomic
      biodiversity, functional biodiversity, and rates of 10 different micropollutant
      biotransformations for 10 full-scale WWTP communities. We have demonstrated that
      biodiversity is positively associated with the rates of specific, but not all,
      micropollutant biotransformations. Thus, one cannot assume whether or how
      biodiversity will associate with the rate of any particular micropollutant
      biotransformation. We have further demonstrated that the strongest positive
      association is between biodiversity and the collective rate of multiple
      micropollutant biotransformations. Thus, more biodiversity is likely required to
      maximize the collective rates of multiple micropollutant biotransformations than
      is required to maximize the rate of any individual micropollutant
      biotransformation. We finally provide evidence that the positive associations are
      stronger for rare micropollutant biotransformations than for common
      micropollutant biotransformations. Together, our results are consistent with the
      hypothesis that differences in biodiversity can indeed translate into differences
      in the provision of particular ecosystem services by full-scale WWTP communities.

PMID- 25398863
TI  - Comparison of oxidation kinetics of nitrite-oxidizing bacteria: nitrite
      availability as a key factor in niche differentiation.
AB  - Nitrification has an immense impact on nitrogen cycling in natural ecosystems and
      in wastewater treatment plants. Mathematical models function as tools to capture
      the complexity of these biological systems, but kinetic parameters especially of
      nitrite-oxidizing bacteria (NOB) are lacking because of a limited number of pure
      cultures until recently. In this study, we compared the nitrite oxidation
      kinetics of six pure cultures and one enrichment culture representing three
      genera of NOB (Nitrobacter, Nitrospira, Nitrotoga). With half-saturation
      constants (Km) between 9 and 27 MUM nitrite, Nitrospira bacteria are adapted to
      live under significant substrate limitation. Nitrobacter showed a wide range of
      lower substrate affinities, with Km values between 49 and 544 MUM nitrite.
      However, the advantage of Nitrobacter emerged under excess nitrite supply,
      sustaining high maximum specific activities (Vmax) of 64 to 164 MUmol nitrite/mg
      protein/h, contrary to the lower activities of Nitrospira of 18 to 48 MUmol
      nitrite/mg protein/h. The Vmax (26 MUmol nitrite/mg protein/h) and Km (58 MUM
      nitrite) of "Candidatus Nitrotoga arctica" measured at a low temperature of 17
      degrees C suggest that Nitrotoga can advantageously compete with other NOB,
      especially in cold habitats. The kinetic parameters determined represent improved
      basis values for nitrifying models and will support predictions of community
      structure and nitrification rates in natural and engineered ecosystems. 

PMID- 25398864
TI  - High levels of antimicrobial resistance among escherichia coli isolates from
      livestock farms and synanthropic rats and shrews in the Mekong Delta of Vietnam.
AB  - In Mekong Delta farms (Vietnam), antimicrobials are extensively used, but limited
      data are available on levels of antimicrobial resistance (AMR) among Escherichia
      coli isolates. We performed a structured survey of AMR in E. coli isolates (n =
      434) from 90 pig, chicken, and duck farms. The results were compared with AMR
      among E. coli isolates (n = 234) from 66 small wild animals (rats and shrews)
      trapped on farms and in forests and rice fields. The isolates were susceptibility
      tested against eight antimicrobials. E. coli isolates from farmed animals were
      resistant to a median of 4 (interquartile range [IQR], 3 to 6) antimicrobials
      versus 1 (IQR, 1 to 2) among wild mammal isolates (P < 0.001). The prevalences of
      AMR among farmed species isolates (versus wild animals) were as follows:
      tetracycline, 84.7% (versus 25.6%); ampicillin, 78.9% (versus 85.9%);
      trimethoprim-sulfamethoxazole, 52.1% (versus 18.8%); chloramphenicol, 39.9%
      (versus 22.5%); amoxicillin-clavulanic acid, 36.6% (versus 34.5%); and
      ciprofloxacin, 24.9% (versus 7.3%). The prevalence of multidrug resistance (MDR)
      (resistance against three or more antimicrobial classes) among pig isolates was
      86.7% compared to 66.9 to 72.7% among poultry isolates. After adjusting for host
      species, MDR was ~8 times greater among isolates from wild mammals trapped on
      farms than among those trapped in forests/rice fields (P < 0.001). Isolates were
      assigned to unique profiles representing their combinations of susceptibility
      results. Multivariable analysis of variance indicated that AMR profiles from wild
      mammals trapped on farms and those from domestic animals were more alike (R(2)
      range, 0.14 to 0.30) than E. coli isolates from domestic animals and mammals
      trapped in the wild (R(2) range, 0.25 to 0.45). The results strongly suggest that
      AMR on farms is a key driver of environmental AMR in the Mekong Delta. 

PMID- 25398865
TI  - Ecological succession and viability of human-associated microbiota on restroom
      surfaces.
AB  - Human-associated bacteria dominate the built environment (BE). Following
      decontamination of floors, toilet seats, and soap dispensers in four public
      restrooms, in situ bacterial communities were characterized hourly, daily, and
      weekly to determine their successional ecology. The viability of cultivable
      bacteria, following the removal of dispersal agents (humans), was also assessed
      hourly. A late-successional community developed within 5 to 8 h on restroom
      floors and showed remarkable stability over weeks to months. Despite late
      successional dominance by skin- and outdoor-associated bacteria, the most
      ubiquitous organisms were predominantly gut-associated taxa, which persisted
      following exclusion of humans. Staphylococcus represented the majority of the
      cultivable community, even after several hours of human exclusion. Methicillin
      resistant Staphylococcus aureus (MRSA)-associated virulence genes were found on
      floors but were not present in assembled Staphylococcus pan-genomes. Viral
      abundances, which were predominantly enterophages, human papilloma virus, and
      herpesviruses, were significantly correlated with bacterial abundances and showed
      an unexpectedly low virus-to-bacterium ratio in surface-associated samples,
      suggesting that bacterial hosts are mostly dormant on BE surfaces. 

PMID- 25398866
TI  - MomL, a novel marine-derived N-acyl homoserine lactonase from Muricauda olearia.
AB  - Gram-negative bacteria use N-acyl homoserine lactones (AHLs) as quorum sensing
      (QS) signaling molecules for interspecies communication, and AHL-dependent QS is
      related with virulence factor production in many bacterial pathogens. Quorum
      quenching, the enzymatic degradation of the signaling molecule, would attenuate
      virulence rather than kill the pathogens, and thereby reduce the potential for
      evolution of drug resistance. In a previous study, we showed that Muricauda
      olearia Th120, belonging to the class Flavobacteriia, has strong AHL degradative
      activity. In this study, an AHL lactonase (designated MomL), which could degrade
      both short- and long-chain AHLs with or without a substitution of oxo-group at
      the C-3 position, was identified from Th120. Liquid chromatography-mass
      spectrometry analysis demonstrated that MomL functions as an AHL lactonase
      catalyzing AHL degradation through lactone hydrolysis. MomL is an AHL lactonase
      belonging to the metallo-beta-lactamase superfamily that harbors an N-terminal
      signal peptide. The overall catalytic efficiency of MomL for C6-HSL is ~2.9 *
      10(5) s(-1) M(-1). Metal analysis and site-directed mutagenesis showed that,
      compared to AiiA, MomL has a different metal-binding capability and requires the
      histidine and aspartic acid residues for activity, while it shares the "HXHXDH"
      motif with other AHL lactonases belonging to the metallo-beta-lactamase
      superfamily. This suggests that MomL is a representative of a novel type of
      secretory AHL lactonase. Furthermore, MomL significantly attenuated the virulence
      of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model, which
      suggests that MomL has the potential to be used as a therapeutic agent. 

PMID- 25398867
TI  - Propionyl coenzyme A (propionyl-CoA) carboxylase in Haloferax mediterranei:
      Indispensability for propionyl-CoA assimilation and impacts on global metabolism.
AB  - Propionyl coenzyme A (propionyl-CoA) is an important intermediate during the
      biosynthesis and catabolism of intracellular carbon storage of poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) in haloarchaea. However, the
      haloarchaeal propionyl-CoA carboxylase (PCC) and its physiological significance
      remain unclear. In this study, we identified a PCC that catalyzed propionyl-CoA
      carboxylation with an acetyl-CoA carboxylation side activity in Haloferax
      mediterranei. Gene knockout/complementation demonstrated that the PCC enzyme
      consisted of a fusion protein of a biotin carboxylase and a biotin-carboxyl
      carrier protein (PccA [HFX_2490]), a carboxyltransferase component (PccB
      [HFX_2478]), and an essential small subunit (PccX [HFX_2479]). Knockout of pccBX
      led to an inability to utilize propionate and a higher intracellular propionyl
      CoA level, indicating that the PCC enzyme is indispensable for propionyl-CoA
      utilization. Interestingly, H. mediterranei DBX (pccBX-deleted strain) displayed
      multiple phenotypic changes, including retarded cell growth, decreased glucose
      consumption, impaired PHBV biosynthesis, and wrinkled cells. A propionyl-CoA
      concentration equivalent to the concentration that accumulated in DBX cells was
      demonstrated to inhibit succinyl-CoA synthetase of the tricarboxylic acid cycle
      in vitro. Genome-wide microarray analysis showed that many genes for glycolysis,
      pyruvate oxidation, PHBV accumulation, electron transport, and stress responses
      were affected in DBX. This study not only identified the haloarchaeal PCC for the
      metabolism of propionyl-CoA, an important intermediate in haloarchaea, but also
      demonstrated that impaired propionyl-CoA metabolism affected global metabolism in
      H. mediterranei. 

PMID- 25398869
TI  - Transcriptomic and physiological insights into the robustness of long filamentous
      cells of Methanosaeta harundinacea, prevalent in upflow anaerobic sludge blanket
      granules.
AB  - Methanosaeta spp. are widely distributed in natural environments, and their
      filamentous cells contribute significantly to sludge granulation and the good
      performance of anaerobic reactors. A previous study indicated that Methanosaeta
      harundinacea 6Ac displays a quorum sensing-regulated morphological transition
      from short to long filaments, and more acetate is channeled into methane
      production in long filaments, whereas more is channeled into biomass synthesis in
      short filaments. Here, we performed transcriptomic and physiological analysis to
      gain insights into active methanogenesis in long filaments of M. harundinacea
      6Ac. Both RNA sequencing (RNA-seq) and quantitative reverse transcription-PCR
      indicated that transcription of the genes involved in aceticlastic methanogenesis
      and energy metabolism was upregulated 1.2- to 10.3-fold in long filaments, while
      transcription of the genes for the methyl oxidative shunt was upregulated in
      short filaments. [2-(13)C]acetate trace experiments demonstrated that a
      relatively higher portion of the acetate methyl group was oxidized to CO2 in
      short filaments than in long filaments. The long filaments exhibited higher
      catalase activity and oxygen tolerance than the short ones, which is consistent
      with increased transcription of the oxidant-scavenging genes. Moreover,
      transcription of genes for cell surface structures was upregulated in the long
      filaments, and transmission electron microscopy revealed a thicker cell envelope
      in the filaments. RNA-seq determined a >2-fold upregulation of a variety of
      antistress genes in short filaments, like those encoding chaperones and DNA
      repair systems, which implies that the short filaments can be stressed. This
      study reveals the genetic basis for the prevalence of the long filamentous
      morphology of M. harundinacea cells in upflow anaerobic sludge blanket granules. 

PMID- 25398868
TI  - Dysbiosis and alterations in predicted functions of the subgingival microbiome in
      chronic periodontitis.
AB  - Chronic periodontitis is an inflammatory disease of the periodontium affecting
      nearly 65 million adults in the United States. Changes in subgingival microbiota
      have long been associated with chronic periodontitis. Recent culture-independent
      molecular studies have revealed the immense richness and complexity of oral
      microbial communities. However, data sets across studies have not been directly
      compared, and whether the observed microbial variations are consistent across
      different studies is not known. Here, we used 16S rRNA sequencing to survey the
      subgingival microbiota in 25 subjects with chronic periodontal disease and 25
      healthy controls and compared our data sets with those of three previously
      reported microbiome studies. Consistent with data from previous studies, our
      results demonstrate a significantly altered microbial community structure with
      decreased heterogeneity in periodontal disease. Comparison with data from three
      previously reported studies revealed that subgingival microbiota clustered by
      study. However, differences between periodontal health and disease were larger
      than the technical variations across studies. Using a prediction score and
      applying five different distance metrics, we observed two predominant clusters.
      One cluster was driven by Fusobacterium and Porphyromonas and was associated with
      clinically apparent periodontitis, and the second cluster was dominated by Rothia
      and Streptococcus in the majority of healthy sites. The predicted functional
      capabilities of the periodontitis microbiome were significantly altered. Genes
      involved in bacterial motility, energy metabolism, and lipopolysaccharide
      biosynthesis were overrepresented in periodontal disease, whereas genes
      associated with transporters, the phosphotransferase system, transcription
      factors, amino acid biosynthesis, and glycolysis/gluconeogenesis were enriched in
      healthy controls. These results demonstrate significant alterations in microbial
      composition and function in periodontitis and suggest genes and metabolic
      pathways associated with periodontal disease. 

PMID- 25398870
TI  - Metabolic engineering of Escherichia coli for the synthesis of the plant
      polyphenol pinosylvin.
AB  - Plant polyphenols are of great interest for drug discovery and drug development
      since many of these compounds have health-promoting activities as treatments
      against various diseases, such as diabetes, cancer, or heart diseases. However,
      the limited availability of polyphenols represents a major obstacle to clinical
      applications that must be overcome. In comparison to the quantities of these
      compounds obtained by isolation from natural sources or costly chemical
      synthesis, the microbial production of these compounds could provide sufficient
      quantities from inexpensive substrates. In this work, we describe the development
      of an Escherichia coli platform strain for the production of pinosylvin, a
      stilbene found in the heartwood of pine trees which could aid in the treatment of
      various cancers and cardiovascular diseases. Initially, several configurations of
      the three-step biosynthetic pathway to pinosylvin were constructed from a set of
      two different enzymes for each enzymatic step. After optimization of gene
      expression and evaluation of different construct environments, low pinosylvin
      concentrations up to 3 mg/liter could be detected. Analysis of the precursor
      supply and a comparative analysis of the intracellular pools of pathway
      intermediates and product identified the limited malonyl coenzyme A (malonyl-CoA)
      availability and low stilbene synthase activity in the heterologous host to be
      the main bottlenecks during pinosylvin production. Addition of cerulenin for
      increasing intracellular malonyl-CoA pools and the in vivo evolution of the
      stilbene synthase from Pinus strobus for improved activity in E. coli proved to
      be the keys to elevated product titers. These measures allowed product titers of
      70 mg/liter pinosylvin from glucose, which could be further increased to 91
      mg/liter by the addition of l-phenylalanine. 

PMID- 25398871
TI  - Role of secondary metabolites in establishment of the mutualistic partnership
      between Xenorhabdus nematophila and the entomopathogenic nematode Steinernema
      carpocapsae.
AB  - Xenorhabdus nematophila engages in a mutualistic partnership with the nematode
      Steinernema carpocapsae, which invades insects, migrates through the gut, and
      penetrates into the hemocoel (body cavity). We showed previously that during
      invasion of Manduca sexta, the gut microbe Staphylococcus saprophyticus appeared
      transiently in the hemocoel, while Enterococcus faecalis proliferated as X.
      nematophila became dominant. X. nematophila produces diverse secondary
      metabolites, including the major water-soluble antimicrobial xenocoumacin. Here,
      we study the role of X. nematophila antimicrobials in interspecies competition
      under biologically relevant conditions using strains lacking either xenocoumacin
      (DeltaxcnKL strain), xenocoumacin and the newly discovered antibiotic F
      (DeltaxcnKL:F strain), or all ngrA-derived secondary metabolites (ngrA strain).
      Competition experiments were performed in Grace's insect medium, which is based
      on lepidopteran hemolymph. S. saprophyticus was eliminated when inoculated into
      growing cultures of either the DeltaxcnKL strain or DeltaxcnKL:F strain but grew
      in the presence of the ngrA strain, indicating that ngrA-derived antimicrobials,
      excluding xenocoumacin or antibiotic F, were required to eliminate the
      competitor. In contrast, S. saprophyticus was eliminated when coinjected into M.
      sexta with either the DeltaxcnKL or ngrA strain, indicating that ngrA-derived
      antimicrobials were not required to eliminate the competitor in vivo. E. faecalis
      growth was facilitated when coinjected with either of the mutant strains.
      Furthermore, nematode reproduction in M. sexta naturally infected with infective
      juveniles colonized with the ngrA strain was markedly reduced relative to the
      level of reproduction when infective juveniles were colonized with the wild-type
      strain. These findings provide new insights into interspecies competition in a
      host environment and suggest that ngrA-derived compounds serve as signals for in
      vivo nematode reproduction. 

PMID- 25398873
TI  - Antidepressant exposure during the first trimester does not increase the risk of
      cardiac malformations in infants.

PMID- 25398872
TI  - Pseudomonas strains naturally associated with potato plants produce volatiles
      with high potential for inhibition of Phytophthora infestans.
AB  - Bacteria emit volatile organic compounds with a wide range of effects on
      bacteria, fungi, plants, and animals. The antifungal potential of bacterial
      volatiles has been investigated with a broad span of phytopathogenic organisms,
      yet the reaction of oomycetes to these volatile signals is largely unknown. For
      instance, the response of the late blight-causing agent and most devastating
      oomycete pathogen worldwide, Phytophthora infestans, to bacterial volatiles has
      not been assessed so far. In this work, we analyzed this response and compared it
      to that of selected fungal and bacterial potato pathogens, using newly isolated,
      potato-associated bacterial strains as volatile emitters. P. infestans was highly
      susceptible to bacterial volatiles, while fungal and bacterial pathogens were
      less sensitive. Cyanogenic Pseudomonas strains were the most active, leading to
      complete growth inhibition, yet noncyanogenic ones also produced antioomycete
      volatiles. Headspace analysis of the emitted volatiles revealed 1-undecene as a
      compound produced by strains inducing volatile-mediated P. infestans growth
      inhibition. Supplying pure 1-undecene to P. infestans significantly reduced
      mycelial growth, sporangium formation, germination, and zoospore release in a
      dose-dependent manner. This work demonstrates the high sensitivity of P.
      infestans to bacterial volatiles and opens new perspectives for sustainable
      control of this devastating pathogen. 

PMID- 25398874
TI  - Surfactant toxicity in a case of (4-chloro-2-methylphenoxy) acetic acid herbicide
      intoxication.
AB  - OBJECTIVE: Self-poisoning with (4-chloro-2-methylphenoxy) acetic acid (MCPA) is a
      common reason for presentation to hospitals, especially in some Asian countries.
      We encountered a case of a 76-year-old woman who experienced unconsciousness,
      shock and respiratory failure after ingesting 100 mL MCPA herbicide. We
      determined whether the surfactant in the formulation was the chemical responsible
      for the toxic symptom in this patient. DESIGN: 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) cell viability and lactate dehydrogenase (LDH)
      cytotoxicity assays were performed on human brain neuroblastoma SK-N-SH cells.
      The expressions of 84 genes in 9 categories that are implicated in cellular
      damage pathways were quantified using an RT(2) ProfilerTM PCR array on a human
      neuronal cell line challenged with polyoxyethylene tridecyl ether (PTE). SETTING:
      Pesticide intoxication institute in university hospital. INTERVENTIONS:
      Extracorporeal elimination with intravenous lipid emulsion. MEASUREMENTS: Cell
      viability and gene expression. MAIN RESULTS: In the MTT assay, MCPA only
      minimally decreased cell viability even at concentrations as high as 1 mM. Cells
      treated with 1-methoxy-2-propanol, dimethylamine and polypropylene glycol
      exhibited minimal decreases in viability, whilst the viability of cells
      challenged with PTE decreased dramatically; only 15.5% of cells survived after
      exposure to 1 uM PTE. Similarly, the results of the LDH cytotoxicity assay showed
      that MCPA had very low cytotoxicity, whilst cells treated with PTE showed
      incomparably higher LDH levels (p < 0.0001). PTE up-regulated the expressions of
      genes implicated in various cell damage pathways, particularly genes involved in
      the inflammatory pathway. CONCLUSIONS: The surfactant PTE was likely the chemical
      responsible for the toxic symptom in our patient.

PMID- 25398875
TI  - The putative cellodextrin transporter-like protein CLP1 is involved in cellulase
      induction in Neurospora crassa.
AB  - Neurospora crassa recently has become a novel system to investigate cellulase
      induction. Here, we discovered a novel membrane protein, cellodextrin transporter
      like protein 1 (CLP1; NCU05853), a putative cellodextrin transporter-like protein
      that is a critical component of the cellulase induction pathway in N. crassa.
      Although CLP1 protein cannot transport cellodextrin, the suppression of cellulase
      induction by this protein was discovered on both cellobiose and Avicel. The co
      disruption of the cellodextrin transporters cdt2 and clp1 in strain Delta3betaG
      formed strain CPL7. With induction by cellobiose, cellulase production was
      enhanced 6.9-fold in CPL7 compared with Delta3betaG. We also showed that the
      suppression of cellulase expression by CLP1 occurred by repressing the expression
      of cellodextrin transporters, particularly cdt1 expression. Transcriptome
      analysis of the hypercellulase-producing strain CPL7 showed that the cellulase
      expression machinery was dramatically stimulated, as were the cellulase enzyme
      genes including the inducer transporters and the major transcriptional
      regulators. 

PMID- 25398876
TI  - Evaluation of anti-HIV-1 mutagenic nucleoside analogues.
AB  - Because of their high mutation rates, RNA viruses and retroviruses replicate
      close to the threshold of viability. Their existence as quasi-species has
      pioneered the concept of "lethal mutagenesis" that prompted us to synthesize
      pyrimidine nucleoside analogues with antiviral activity in cell culture
      consistent with an accumulation of deleterious mutations in the HIV-1 genome.
      However, testing all potentially mutagenic compounds in cell-based assays is
      tedious and costly. Here, we describe two simple in vitro biophysical/biochemical
      assays that allow prediction of the mutagenic potential of deoxyribonucleoside
      analogues. The first assay compares the thermal stabilities of matched and
      mismatched base pairs in DNA duplexes containing or not the nucleoside analogues
      as follows. A promising candidate should display a small destabilization of the
      matched base pair compared with the natural nucleoside and the smallest gap
      possible between the stabilities of the matched and mismatched base pairs. From
      this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'
      deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The
      second in vitro reverse transcription assay assesses DNA synthesis opposite
      nucleoside analogues inserted into a template strand and subsequent extension of
      the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'
      deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient
      mutagens. The predictive potential of our fast and easy first line screens was
      confirmed by detailed analysis of the mutation spectrum induced by the compounds
      in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5
      hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by
      3.1- and 3.4-fold, respectively. 

PMID- 25398877
TI  - Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces integrin
      activation through direct binding to a newly identified binding site (site 2) in
      integrins alphavbeta3, alpha4beta1, and alpha5beta1.
AB  - Integrins are activated by signaling from inside the cell (inside-out signaling)
      through global conformational changes of integrins. We recently discovered that
      fractalkine activates integrins in the absence of CX3CR1 through the direct
      binding of fractalkine to a ligand-binding site in the integrin headpiece (site
      2) that is distinct from the classical RGD-binding site (site 1). We propose that
      fractalkine binding to the newly identified site 2 induces activation of site 1
      though conformational changes (in an allosteric mechanism). We reasoned that site
      2-mediated activation of integrins is not limited to fractalkine. Human secreted
      phospholipase A2 type IIA (sPLA2-IIA), a proinflammatory protein, binds to
      integrins alphavbeta3 and alpha4beta1 (site 1), and this interaction initiates a
      signaling pathway that leads to cell proliferation and inflammation. Human sPLA2
      IIA does not bind to M-type receptor very well. Here we describe that sPLA2-IIA
      directly activated purified soluble integrin alphavbeta3 and transmembrane
      alphavbeta3 on the cell surface. This activation did not require catalytic
      activity or M-type receptor. Docking simulation predicted that sPLA2-IIA binds to
      site 2 in the closed-headpiece of alphavbeta3. A peptide from site 2 of integrin
      beta1 specifically bound to sPLA2-IIA and suppressed sPLA2-IIA-induced integrin
      activation. This suggests that sPLA2-IIA activates alphavbeta3 through binding to
      site 2. sPLA2-IIA also activated integrins alpha4beta1 and alpha5beta1 in a site
      2-mediated manner. We recently identified small compounds that bind to sPLA2-IIA
      and suppress integrin-sPLA2-IIA interaction (e.g. compound 21 (Cmpd21)). Cmpd21
      effectively suppressed sPLA2-IIA-induced integrin activation. These results
      define a novel mechanism of proinflammatory action of sPLA2-IIA through integrin
      activation. 

PMID- 25398878
TI  - Characterization of the Vibrio vulnificus 1-Cys peroxiredoxin Prx3 and regulation
      of its expression by the Fe-S cluster regulator IscR in response to oxidative
      stress and iron starvation.
AB  - Peroxiredoxins (Prxs) are ubiquitous antioxidant enzymes that reduce toxic
      peroxides. A new Vibrio vulnificus Prx, named Prx3, was identified and
      characterized in this study. Biochemical and mutational analyses revealed that
      Prx3 reduces H2O2, utilizing glutaredoxin 3 (Grx3) and glutathione (GSH) as
      reductants, and requires only N-terminal peroxidatic cysteine for its catalysis.
      These results, combined with the monomeric size of Prx3 observed under non
      reducing conditions, suggested that Prx3 is a Grx3/GSH-dependent 1-Cys Prx and
      oxidized without forming intermolecular disulfide bonds. The prx3 mutation
      impaired growth in the medium containing peroxides and reduced virulence in mice,
      indicating that Prx3 is essential for survival under oxidative stress and
      pathogenesis of V. vulnificus. The Fe-S cluster regulator IscR activates prx3 by
      direct binding to a specific binding sequence centered at -44 from the
      transcription start site. The binding sequence was homologous to the Type 2 IscR
      binding sequence, most likely recognized by the Fe-S clusterless apo-IscR in
      Escherichia coli. The iscR3CA mutant, chromosomally encoding the apo-locked IscR,
      exhibited 3-fold higher levels of activation of prx3 than the wild type and
      accumulated more IscR3CA protein in cells. The IscR-dependent activation of prx3
      by aerobic growth and iron starvation was also associated with the increase in
      cellular levels of IscR protein. Taken together, the results suggested that IscR
      senses iron starvation as well as reactive oxygen species and shifts to the apo
      form, which leads to the increase of cellular IscR and in turn prx3 expression,
      contributing to the survival and virulence of V. vulnificus during pathogenesis. 

PMID- 25398879
TI  - Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of
      persulfide sulfur and iron and requirements for GTP, NADH, and ATP.
AB  - Iron-sulfur (Fe-S) clusters are essential cofactors, and mitochondria contain
      several Fe-S proteins, including the [4Fe-4S] protein aconitase and the [2Fe-2S]
      protein ferredoxin. Fe-S cluster assembly of these proteins occurs within
      mitochondria. Although considerable data exist for yeast mitochondria, this
      biosynthetic process has never been directly demonstrated in mammalian
      mitochondria. Using [(35)S]cysteine as the source of sulfur, here we show that
      mitochondria isolated from Cath.A-derived cells, a murine neuronal cell line, can
      synthesize and insert new Fe-(35)S clusters into aconitase and ferredoxins. The
      process requires GTP, NADH, ATP, and iron, and hydrolysis of both GTP and ATP is
      necessary. Importantly, we have identified the (35)S-labeled persulfide on the
      NFS1 cysteine desulfurase as a genuine intermediate en route to Fe-S cluster
      synthesis. In physiological settings, the persulfide sulfur is released from NFS1
      and transferred to a scaffold protein, where it combines with iron to form an Fe
      S cluster intermediate. We found that the release of persulfide sulfur from NFS1
      requires iron, showing that the use of iron and sulfur for the synthesis of Fe-S
      cluster intermediates is a highly coordinated process. The release of persulfide
      sulfur also requires GTP and NADH, probably mediated by a GTPase and a reductase,
      respectively. ATP, a cofactor for a multifunctional Hsp70 chaperone, is not
      required at this step. The experimental system described here may help to define
      the biochemical basis of diseases that are associated with impaired Fe-S cluster
      biogenesis in mitochondria, such as Friedreich ataxia. 

PMID- 25398880
TI  - Pre-steady-state kinetic and structural analysis of interaction of methionine
      gamma-lyase from Citrobacter freundii with inhibitors.
AB  - Methionine gamma-lyase (MGL) catalyzes the gamma-elimination of l-methionine and
      its derivatives as well as the beta-elimination of l-cysteine and its analogs.
      These reactions yield alpha-keto acids and thiols. The mechanism of chemical
      conversion of amino acids includes numerous reaction intermediates. The detailed
      analysis of MGL interaction with glycine, l-alanine, l-norvaline, and l
      cycloserine was performed by pre-steady-state stopped-flow kinetics. The
      structure of side chains of the amino acids is important both for their binding
      with enzyme and for the stability of the external aldimine and ketimine
      intermediates. X-ray structure of the MGL.l-cycloserine complex has been solved
      at 1.6 A resolution. The structure models the ketimine intermediate of
      physiological reaction. The results elucidate the mechanisms of the intermediate
      interconversion at the stages of external aldimine and ketimine formation. 

PMID- 25398881
TI  - Heat shock 70-kDa protein 5 (Hspa5) is essential for pronephros formation by
      mediating retinoic acid signaling.
AB  - Heat shock 70-kDa protein 5 (Hspa5), also known as binding immunoglobulin protein
      (Bip) or glucose-regulated protein 78 (Grp78), belongs to the heat shock protein
      70 kDa family. As a multifunctional protein, it participates in protein folding
      and calcium homeostasis and serves as an essential regulator of the endoplasmic
      reticulum (ER) stress response. It has also been implicated in signal
      transduction by acting as a receptor or co-receptor residing at the plasma
      membrane. Its function during embryonic development, however, remains largely
      elusive. In this study, we used morpholino antisense oligonucleotides (MOs) to
      knock down Hspa5 activity in Xenopus embryos. In Hspa5 morphants, pronephros
      formation was strongly inhibited with the reduction of pronephric marker genes
      Lim homeobox protein 1 (lhx1), pax2, and beta1 subunit of Na/K-ATPase (atp1b1).
      Pronephros tissue was induced in vitro by treating animal caps with all-trans
      retinoic acid and activin. Depletion of Hspa5 in animal caps, however, blocked
      the induction of pronephros as well as reduced the expression of retinoic acid
      (RA)-responsive genes, suggesting that knockdown of Hspa5 attenuated RA
      signaling. Knockdown of Hspa5 in animal caps resulted in decreased expression of
      lhx1, a transcription factor directly regulated by RA signaling and essential for
      pronephros specification. Co-injection of Hspa5MO with lhx1 mRNA partially
      rescued the phenotype induced by Hspa5MO. These results suggest that the RA-Lhx1
      signaling cascade is involved in Hspa5MO-induced pronephros malformation. This
      study shows that Hspa5, a key regulator of the unfolded protein response, plays
      an essential role in pronephros formation, which is mediated in part through RA
      signaling during early embryonic development. 

PMID- 25398882
TI  - The influenza hemagglutinin fusion domain is an amphipathic helical hairpin that
      functions by inducing membrane curvature.
AB  - The highly conserved N-terminal 23 residues of the hemagglutinin glycoprotein,
      known as the fusion peptide domain (HAfp23), is vital to the membrane fusion and
      infection mechanism of the influenza virus. HAfp23 has a helical hairpin
      structure consisting of two tightly packed amphiphilic helices that rest on the
      membrane surface. We demonstrate that HAfp23 is a new class of amphipathic helix
      that functions by leveraging the negative curvature induced by two tightly packed
      helices on membranes. The helical hairpin structure has an inverted wedge shape
      characteristic of negative curvature lipids, with a bulky hydrophobic region and
      a relatively small hydrophilic head region. The F3G mutation reduces this
      inverted wedge shape by reducing the volume of its hydrophobic base. We show that
      despite maintaining identical backbone structures and dynamics as the wild type
      HAfp23, the F3G mutant has an attenuated fusion activity that is correlated to
      its reduced ability to induce negative membrane curvature. The inverted wedge
      shape of HAfp23 is likely to play a crucial role in the initial stages of
      membrane fusion by stabilizing negative curvature in the fusion stalk. 

PMID- 25398884
TI  - Effect of preeclampsia on umbilical cord blood stem cells in relation to breast
      cancer susceptibility in the offspring.
AB  - Women born from a preeclamptic (PE) pregnancy are associated with a lower risk of
      breast cancer. Prenatal and early-life exposures are hypothesized to influence
      breast cancer susceptibility through their effect on stem cells. We examined stem
      cell populations in umbilical cord blood from PE pregnancies and compared with
      those from pregnancies without this condition. We isolated mononuclear cells from
      58 PE and 197 normotensive (non-PE) umbilical cord blood samples and examined the
      different stem cell populations. Hematopoietic (CD34(+) and CD34(+)CD38(-)),
      endothelial (CD34(+)CD133(+), CD34(+)VEGFR2(+), CD133(+)VEGFR2(+) and
      CD34(+)CD133(+)VEGFR2(+)), and putative breast (EpCAM(+), EpCAM(+)CD49f(+),
      EpCAM(+)CD49f(+)CD117(+), CD49f(+)CD24(+), CD24(+)CD29(+) and
      CD24(+)CD29(+)CD49f(+)) stem/progenitor cell subpopulations were quantified by
      flow cytometry and compared between PE and non-PE samples. Hematopoietic CD34(+)
      cell counts were significantly lowered in PE compared with non-PE samples (P =
      0.039, Kruskal-Wallis test). Levels of CD34(+)CD133(+) endothelial progenitor
      cells were also lower in PE samples (P = 0.032, multiple regression analysis).
      EpCAM(+) and EpCAM(+)CD49f(+) putative breast stem cell levels were significantly
      lowered in PE subjects (multiple regression analysis: P = 0.038 and 0.007,
      respectively). Stratifying by newborn gender, EpCAM(+) and EpCAM(+)CD49f(+) stem
      cells were significantly lowered in PE samples of female, but not male, newborns.
      Umbilical cord blood samples from pregnancies complicated by preeclampsia thus
      had significantly lower levels of hematopoietic, endothelial, and putative breast
      stem cells than non-PE controls. With a lowered breast cancer risk for offspring
      of a PE pregnancy, our findings provide support to the hypothesis that
      susceptibility to breast oncogenesis may be affected by conditions and processes
      during the prenatal period. 

PMID- 25398883
TI  - Identification of a second substrate-binding site in solute-sodium symporters.
AB  - The structure of the sodium/galactose transporter (vSGLT), a solute-sodium
      symporter (SSS) from Vibrio parahaemolyticus, shares a common structural fold
      with LeuT of the neurotransmitter-sodium symporter family. Structural alignments
      between LeuT and vSGLT reveal that the crystallographically identified galactose
      binding site in vSGLT is located in a more extracellular location relative to the
      central substrate-binding site (S1) in LeuT. Our computational analyses suggest
      the existence of an additional galactose-binding site in vSGLT that aligns to the
      S1 site of LeuT. Radiolabeled galactose saturation binding experiments indicate
      that, like LeuT, vSGLT can simultaneously bind two substrate molecules under
      equilibrium conditions. Mutating key residues in the individual substrate-binding
      sites reduced the molar substrate-to-protein binding stoichiometry to ~1. In
      addition, the related and more experimentally tractable SSS member PutP (the
      Na(+)/proline transporter) also exhibits a binding stoichiometry of 2. Targeting
      residues in the proposed sites with mutations results in the reduction of the
      binding stoichiometry and is accompanied by severely impaired translocation of
      proline. Our data suggest that substrate transport by SSS members requires both
      substrate-binding sites, thereby implying that SSSs and neurotransmitter-sodium
      symporters share common mechanistic elements in substrate transport.

PMID- 25398886
TI  - Dose hysteria and concern about radiation exposure should not prevent women from
      undergoing life-saving mammography screening.

PMID- 25398885
TI  - Individuals with neurological diseases are at increased risk of fractures within
      180 days of admission to long-term care in Ontario.
AB  - BACKGROUND: Individuals residing in long-term care (LTC) are more likely to have
      a fragility fracture than community-dwelling seniors. The purpose of this study
      was to determine whether the presence of neurological diseases was associated
      with an increased risk of fracture within 180 days of admission to LTC. METHODS:
      This retrospective cohort study used data collected in the LTC setting using the
      Resident Assessment Instrument (RAI) 2.0 during the period from 2006 to 2011
      (N=42,089). Multivariable logistic regression analyses were conducted to
      determine the associations between the presence of neurological conditions and
      incident fractures, with and without adjustment for clinical variables. RESULTS:
      The incident fracture rate for all LTC residents was 2.6% (N=1,094). Neurological
      condition group size ranged from n=21,015 for Alzheimer's disease or related
      dementias (ADRD) to n=21 for muscular dystrophy (MD). The incidence of fracture
      among residents with specific neurological diseases was as follows: ADRD, 3.2%
      (n=672), MD, 4.8% (n=1), Parkinson's disease, 2.5% (n=57), stroke, 2.3% (n=166),
      epilepsy, 2.5% (n=38), Huntington's disease, 1.4% (n=1), multiple sclerosis, 0.3%
      (n=1) and traumatic brain injury, 3.8% (n=11); among the comparison group with no
      neurological conditions, the fracture rate was 2.0% (n=366). The neurological
      diseases that were associated with a significantly greater odds of having an
      incident fracture in the first 180 days of LTC admission were as follows: ADRD
      (1.3; 95% CI: 1.1-1.5), epilepsy (1.5; 95% CI: 1.0-2.1) and traumatic brain
      injury (2.7; 95% CI: 1.4-5.0). CONCLUSION: LTC residents with ADRD, epilepsy and
      traumatic brain injury are at a higher risk for sustaining an incident fracture
      in the first 180 days of admission and should be considered for fracture
      prevention strategies.

PMID- 25398888
TI  - Socioeconomic inequalities in quality of care and outcomes among patients with
      acute coronary syndrome in the modern era of drug eluting stents.
AB  - BACKGROUND: The rapidly changing landscape of percutaneous coronary intervention
      provides a unique model for examining disparities over time. Previous studies
      have not examined socioeconomic inequalities in the current era of drug eluting
      stents (DES). METHODS AND RESULTS: We analyzed 835 070 hospitalizations for acute
      coronary syndrome (ACS) from the Healthcare Cost and Utilization Project across
      all insurance types from 2008 to 2011, examining whether quality of care and
      outcomes for patients with ACS differed by income (based on zip code of
      residence) with adjustment for patient characteristics and clustering by
      hospital. We found that lower-income patients were less likely to receive an
      angiogram within 24 hours of a ST elevation myocardial infarction (STEMI) (69.5%
      for IQ1 versus 73.7% for IQ4, P<0.0001, OR 0.79 [0.68 to 0.91]) or within 48
      hours of a Non-STEMI (47.6% for IQ1 versus 51.8% for IQ4, P<0.0001, OR 0.86 [0.75
      to 0.99]). Lower income was associated with less use of a DES (64.7% for IQ1
      versus 71.2% for IQ4, P<0.0001, OR 0.83 [0.74 to 0.93]). However, no differences
      were found for coronary artery bypass surgery. Among STEMI patients, lower-income
      patients also had slightly increased adjusted mortality rates (10.8% for IQ1
      versus 9.4% for IQ4, P<0.0001, OR 1.17 [1.11 to 1.25]). After further adjusting
      for time to reperfusion among STEMI patients, mortality differences across income
      groups decreased. CONCLUSIONS: For the most well accepted procedural treatments
      for ACS, income inequalities have faded. However, such inequalities have
      persisted for DES use, a relatively expensive and until recently, controversial
      revascularization procedure. Differences in mortality are significantly
      associated with differences in time to primary PCI, suggesting an important
      target for understanding why these inequalities persist.

PMID- 25398890
TI  - Ethnicity and differences between clinic and ambulatory blood pressure
      measurements.
AB  - BACKGROUND: This study investigated the relationship of ethnicity to the
      differences between blood pressure (BP) measured in a clinic setting and by
      ambulatory blood pressure monitoring (ABPM) in individuals with a previous
      diagnosis of hypertension (HT) and without a previous diagnosis of hypertension
      (NHT). METHODS: A cross-sectional comparison of BP measurement was performed in
      770 participants (white British (WB, 39%), South Asian (SA, 31%), and African
      Caribbean (AC, 30%)) in 28 primary care clinics in West Midlands, United Kingdom.
      Mean differences between daytime ABPM, standardized clinic (mean of 3 occasions),
      casual clinic (first reading on first occasion), and last routine BP taken at the
      general practitioner practice were compared in HT and NHT individuals. RESULTS:
      Daytime systolic and diastolic ABPM readings were similar to standardized clinic
      BP (systolic: 128 (SE 0.9) vs. 125 (SE 0.9) mm Hg (NHT) and 132 (SE 0.7) vs. 131
      (SE 0.7) mm Hg (HT)) and were not associated with ethnicity to a clinically
      important extent. When BP was taken less carefully, differences emerged: casual
      clinic readings were higher than ABPM, particularly in the HT group where the
      systolic differences approached clinical relevance (131 (SE 1.2) vs. 129 (SE 1.0)
      mm Hg (NHT) and 139 (SE 0.9) vs. 133 (SE 0.7) mm Hg (HT)) and were larger in SA
      and AC hypertensive individuals (136 (SE 1.5) vs. 133 (SE 1.2) mm Hg (WB), 141
      (SE 1.7) vs. 133 (SE 1.4) mm Hg (SA), and 142 (SE 1.6) vs. 134 (SE 1.3) mm Hg
      (AC); mean differences: 3 (0-7), P = 0.03 and 4 (1-7), P = 0.01, respectively).
      Differences were also observed for the last practice reading in SA and ACs.
      CONCLUSIONS: BP differences between ethnic groups where BP is carefully measured
      on multiple occasions are small and unlikely to alter clinical management. When
      BP is measured casually on a single occasion or in routine care, differences
      appear that could approach clinical relevance.

PMID- 25398889
TI  - Lifestyle-based prediction model for the prevention of CVD: the Healthy Heart
      Score.
AB  - BACKGROUND: Clinical practice focuses on the primary prevention of cardiovascular
      (CV) disease (CVD) through the modification and pharmacological treatment of
      elevated risk factors. Prediction models based on established risk factors are
      available for use in the primary prevention setting. However, the prevention of
      risk factor development through healthy lifestyle behaviors, or primordial
      prevention, is of paramount importance to achieve optimal population-wide CV
      health and minimize long-term CVD risk. METHODS AND RESULTS: We developed a
      lifestyle-based CVD prediction model among 61 025 women in the Nurses' Health
      Study and 34 478 men in the Health Professionals Follow-up Study, who were free
      of chronic disease in 1986 and followed for <=24 years. Lifestyle factors were
      assessed by questionnaires in 1986. In the derivation step, we used the Bayes
      Information Criterion to create parsimonious 20-year risk prediction models among
      a random two thirds of participants in each cohort separately. The scores were
      validated in the remaining one third of participants in each cohort. Over 24
      years, there were 3775 cases of CVD in women and 3506 cases in men. The Healthy
      Heart Score included age, smoking, body mass index, exercise, alcohol, and a
      composite diet score. In the validation cohort, the risk score demonstrated good
      discrimination (Harrell's C-index, 0.72; 95% confidence interval [CI], 0.71, 0.74
      [women]; 0.77; 95% CI, 0.76, 0.79 [men]), fit, and calibration, particularly
      among individuals without baseline hypertension or hypercholesterolemia.
      CONCLUSIONS: The Healthy Heart Score accurately identifies individuals at
      elevated risk for CVD and may serve as an important clinical and public health
      screening tool for the primordial prevention of CVD.

PMID- 25398893
TI  - Interest level in 2-year-olds with autism spectrum disorder predicts rate of
      verbal, nonverbal, and adaptive skill acquisition.
AB  - Recent studies have suggested that skill acquisition rates for children with
      autism spectrum disorders receiving early interventions can be predicted by child
      motivation. We examined whether level of interest during an Autism Diagnostic
      Observation Schedule assessment at 2 years predicts subsequent rates of verbal,
      nonverbal, and adaptive skill acquisition to the age of 3 years. A total of 70
      toddlers with autism spectrum disorder, mean age of 21.9 months, were scored
      using Interest Level Scoring for Autism, quantifying toddlers' interest in toys,
      social routines, and activities that could serve as reinforcers in an
      intervention. Adaptive level and mental age were measured concurrently (Time 1)
      and again after a mean of 16.3 months of treatment (Time 2). Interest Level
      Scoring for Autism score, Autism Diagnostic Observation Schedule score, adaptive
      age equivalent, verbal and nonverbal mental age, and intensity of intervention
      were entered into regression models to predict rates of skill acquisition.
      Interest level at Time 1 predicted subsequent acquisition rate of adaptive skills
      (R(2) = 0.36) and verbal mental age (R(2) = 0.30), above and beyond the effects
      of Time 1 verbal and nonverbal mental ages and Autism Diagnostic Observation
      Schedule scores. Interest level at Time 1 also contributed (R(2) = 0.30), with
      treatment intensity, to variance in development of nonverbal mental age. 

PMID- 25398894
TI  - A comparison of WISC-IV and SB-5 intelligence scores in adolescents with autism
      spectrum disorder.
AB  - In autism spectrum disorders, results of cognitive testing inform clinical care,
      theories of neurodevelopment, and research design. The Wechsler Intelligence
      Scale for Children and the Stanford-Binet are commonly used in autism spectrum
      disorder evaluations and scores from these tests have been shown to be highly
      correlated in typically developing populations. However, they have not been
      compared in individuals with autism spectrum disorder, whose core symptoms can
      make testing challenging, potentially compromising test reliability. We used a
      within-subjects research design to evaluate the convergent validity between the
      Wechsler Intelligence Scale for Children, 4th ed., and Stanford-Binet, 5th ed.,
      in 40 youth (ages 10-16 years) with autism spectrum disorder. Corresponding
      intelligence scores were highly correlated (r = 0.78 to 0.88), but full-scale
      intelligence quotient (IQ) scores (t(38) = -2.27, p = 0.03, d = -0.16) and verbal
      IQ scores (t(36) = 2.23, p = 0.03; d = 0.19) differed between the two tests. Most
      participants obtained higher full-scale IQ scores on the Stanford-Binet, 5th ed.,
      compared to Wechsler Intelligence Scale for Children, 4th ed., with 14% scoring
      more than one standard deviation higher. In contrast, verbal indices were higher
      on the Wechsler Intelligence Scale for Children, 4th ed., Verbal-nonverbal
      discrepancy classifications were only consistent for 60% of the sample.
      Comparisons of IQ test scores in autism spectrum disorder and other special
      groups are important, as it cannot necessarily be assumed that convergent
      validity findings in typically developing children and adolescents hold true
      across all pediatric populations. 

PMID- 25398895
TI  - Synthesis, biophysical properties and biological activity of second generation
      antisense oligonucleotides containing chiral phosphorothioate linkages.
AB  - Bicyclic oxazaphospholidine monomers were used to prepare a series of
      phosphorothioate (PS)-modified gapmer antisense oligonucleotides (ASOs) with
      control of the chirality of each of the PS linkages within the 10-base gap. The
      stereoselectivity was determined to be 98% for each coupling. The objective of
      this work was to study how PS chirality influences biophysical and biological
      properties of the ASO including binding affinity (Tm), nuclease stability,
      activity in vitro and in vivo, RNase H activation and cleavage patterns (both
      human and E. coli) in a gapmer context. Compounds that had nine or more Sp
      linkages in the gap were found to be poorly active in vitro, while compounds with
      uniform Rp-gaps exhibited activity very similar to that of the stereo-random
      parent ASOs. Conversely, when tested in vivo, the full Rp-gap compound was found
      to be quickly metabolized resulting in low activity. A total of 31 ASOs were
      prepared with control of the PS chirally of each linkage within the gap in an
      attempt to identify favorable Rp/Sp positions. We conclude that a mix of Rp and
      Sp is required to achieve a balance between good activity and nuclease stability.

PMID- 25398896
TI  - FlyBase: introduction of the Drosophila melanogaster Release 6 reference genome
      assembly and large-scale migration of genome annotations.
AB  - Release 6, the latest reference genome assembly of the fruit fly Drosophila
      melanogaster, was released by the Berkeley Drosophila Genome Project in 2014; it
      replaces their previous Release 5 genome assembly, which had been the reference
      genome assembly for over 7 years. With the enormous amount of information now
      attached to the D. melanogaster genome in public repositories and individual
      laboratories, the replacement of the previous assembly by the new one is a major
      event requiring careful migration of annotations and genome-anchored data to the
      new, improved assembly. In this report, we describe the attributes of the new
      Release 6 reference genome assembly, the migration of FlyBase genome annotations
      to this new assembly, how genome features on this new assembly can be viewed in
      FlyBase (http://flybase.org) and how users can convert coordinates for their own
      data to the corresponding Release 6 coordinates. 

PMID- 25398897
TI  - DDMGD: the database of text-mined associations between genes methylated in
      diseases from different species.
AB  - Gathering information about associations between methylated genes and diseases is
      important for diseases diagnosis and treatment decisions. Recent advancements in
      epigenetics research allow for large-scale discoveries of associations of genes
      methylated in diseases in different species. Searching manually for such
      information is not easy, as it is scattered across a large number of electronic
      publications and repositories. Therefore, we developed DDMGD database
      (http://www.cbrc.kaust.edu.sa/ddmgd/) to provide a comprehensive repository of
      information related to genes methylated in diseases that can be found through
      text mining. DDMGD's scope is not limited to a particular group of genes,
      diseases or species. Using the text mining system DEMGD we developed earlier and
      additional post-processing, we extracted associations of genes methylated in
      different diseases from PubMed Central articles and PubMed abstracts. The
      accuracy of extracted associations is 82% as estimated on 2500 hand-curated
      entries. DDMGD provides a user-friendly interface facilitating retrieval of these
      associations ranked according to confidence scores. Submission of new
      associations to DDMGD is provided. A comparison analysis of DDMGD with several
      other databases focused on genes methylated in diseases shows that DDMGD is
      comprehensive and includes most of the recent information on genes methylated in
      diseases. 

PMID- 25398898
TI  - CMPD: cancer mutant proteome database.
AB  - Whole-exome sequencing, which centres on the protein coding regions of
      disease/cancer associated genes, represents the most cost-effective method to
      date for deciphering the association between genetic alterations and diseases.
      Large-scale whole exome/genome sequencing projects have been launched by various
      institutions, such as NCI, Broad Institute and TCGA, to provide a comprehensive
      catalogue of coding variants in diverse tissue samples and cell lines. Further
      functional and clinical interrogation of these sequence variations must rely on
      extensive cross-platforms integration of sequencing information and a proteome
      database that explicitly and comprehensively archives the corresponding mutated
      peptide sequences. While such data resource is a critical for the mass
      spectrometry-based proteomic analysis of exomic variants, no database is
      currently available for the collection of mutant protein sequences that
      correspond to recent large-scale genomic data. To address this issue and serve as
      bridge to integrate genomic and proteomics datasets, CMPD
      (http://cgbc.cgu.edu.tw/cmpd) collected over 2 millions genetic alterations,
      which not only facilitates the confirmation and examination of potential cancer
      biomarkers but also provides an invaluable resource for translational medicine
      research and opportunities to identify mutated proteins encoded by mutated genes.

PMID- 25398899
TI  - An integrated approach for genome annotation of the eukaryotic thermophile
      Chaetomium thermophilum.
AB  - The thermophilic fungus Chaetomium thermophilum holds great promise for
      structural biology. To increase the efficiency of its biochemical and structural
      characterization and to explore its thermophilic properties beyond those of
      individual proteins, we obtained transcriptomics and proteomics data, and
      integrated them with computational annotation methods and a multitude of
      biochemical experiments conducted by the structural biology community. We
      considerably improved the genome annotation of Chaetomium thermophilum and
      characterized the transcripts and expression of thousands of genes. We
      furthermore show that the composition and structure of the expressed proteome of
      Chaetomium thermophilum is similar to its mesophilic relatives. Data were
      deposited in a publicly available repository and provide a rich source to the
      structural biology community. 

PMID- 25398900
TI  - MBGD update 2015: microbial genome database for flexible ortholog analysis
      utilizing a diverse set of genomic data.
AB  - The microbial genome database for comparative analysis (MBGD) (available at
      http://mbgd.genome.ad.jp/) is a comprehensive ortholog database for flexible
      comparative analysis of microbial genomes, where the users are allowed to create
      an ortholog table among any specified set of organisms. Because of the rapid
      increase in microbial genome data owing to the next-generation sequencing
      technology, it becomes increasingly challenging to maintain high-quality
      orthology relationships while allowing the users to incorporate the latest
      genomic data available into an analysis. Because many of the recently
      accumulating genomic data are draft genome sequences for which some complete
      genome sequences of the same or closely related species are available, MBGD now
      stores draft genome data and allows the users to incorporate them into a user
      specific ortholog database using the MyMBGD functionality. In this function,
      draft genome data are incorporated into an existing ortholog table created only
      from the complete genome data in an incremental manner to prevent low-quality
      draft data from affecting clustering results. In addition, to provide high
      quality orthology relationships, the standard ortholog table containing all the
      representative genomes, which is first created by the rapid classification
      program DomClust, is now refined using DomRefine, a recently developed program
      for improving domain-level clustering using multiple sequence alignment
      information. 

PMID- 25398901
TI  - MethHC: a database of DNA methylation and gene expression in human cancer.
AB  - We present MethHC (http://MethHC.mbc.nctu.edu.tw), a database comprising a
      systematic integration of a large collection of DNA methylation data and
      mRNA/microRNA expression profiles in human cancer. DNA methylation is an
      important epigenetic regulator of gene transcription, and genes with high levels
      of DNA methylation in their promoter regions are transcriptionally silent.
      Increasing numbers of DNA methylation and mRNA/microRNA expression profiles are
      being published in different public repositories. These data can help researchers
      to identify epigenetic patterns that are important for carcinogenesis. MethHC
      integrates data such as DNA methylation, mRNA expression, DNA methylation of
      microRNA gene and microRNA expression to identify correlations between DNA
      methylation and mRNA/microRNA expression from TCGA (The Cancer Genome Atlas),
      which includes 18 human cancers in more than 6000 samples, 6548 microarrays and
      12 567 RNA sequencing data. 

PMID- 25398902
TI  - YM500v2: a small RNA sequencing (smRNA-seq) database for human cancer miRNome
      research.
AB  - We previously presented YM500, which is an integrated database for miRNA
      quantification, isomiR identification, arm switching discovery and novel miRNA
      prediction from 468 human smRNA-seq datasets. Here in this updated YM500v2
      database (http://ngs.ym.edu.tw/ym500/), we focus on the cancer miRNome to make
      the database more disease-orientated. New miRNA-related algorithms developed
      after YM500 were included in YM500v2, and, more significantly, more than 8000
      cancer-related smRNA-seq datasets (including those of primary tumors, paired
      normal tissues, PBMC, recurrent tumors, and metastatic tumors) were incorporated
      into YM500v2. Novel miRNAs (miRNAs not included in the miRBase R21) were not only
      predicted by three independent algorithms but also cleaned by a new in silico
      filtration strategy and validated by wetlab data such as Cross-Linked
      ImmunoPrecipitation sequencing (CLIP-seq) to reduce the false-positive rate. A
      new function 'Meta-analysis' is additionally provided for allowing users to
      identify real-time differentially expressed miRNAs and arm-switching events
      according to customer-defined sample groups and dozens of clinical criteria
      tidying up by proficient clinicians. Cancer miRNAs identified hold the potential
      for both basic research and biotech applications. 

PMID- 25398903
TI  - PNRD: a plant non-coding RNA database.
AB  - The first ncRNA found was an alanine tRNA in baker's yeast, and the first
      detected microRNAs (miRNAs) promoted ncRNA research to a whole new level.
      Research on ncRNAs in animals has focused on the medical field, while in plant
      scientists are more concerned with improving agronomic traits. In 2010, we
      constructed a plant miRNA database named PMRD to meet the demand for miRNA
      research in plants. To provide a way to do fundamental research on plant ncRNAs
      and take full advantage of tremendous public resources, we designed an updated
      platform called plant ncRNA database (PNRD) based on its predecessor PMRD, which
      is accessible at http://structuralbiology.cau.edu.cn/PNRD. We collected a total
      of 25739 entries of 11 different types of ncRNAs from 150 plant species. Targets
      of miRNAs were extended to 178138 pairs in 46 species, while the number of miRNA
      expression profiles reached 35. Improvements in PNRD are not only the larger
      amounts of data, but also better service, such as a more user-friendly interface,
      more multifunctional and browsing options and more background data for users to
      download. We also integrated currently prevalent technologies and toolkits to
      strengthen the capability of the database and provide a one-stop service for
      scientific users. 

PMID- 25398904
TI  - Locating the uracil-5-yl radical formed upon photoirradiation of 5-bromouracil
      substituted DNA.
AB  - In a previous study, we found that 2-deoxyribonolactone is effectively generated
      in the specific 5-bromouracil ((Br)U)-substituted sequence 5'-(G/C)[A]n = 1,2
      (Br)U(Br)U-3' and proposed that a formed uracil-5-yl radical mainly abstracts the
      C1' hydrogen from the 5'-side of (Br)U(Br)U under 302-nm irradiation condition.
      In the present work, we performed photoirradiation of (Br)U-substituted DNA in
      the presence of a hydrogen donor, tetrahydrofuran, to quench the uracil-5-yl
      radical to uracil and then subjected the sample to uracil DNA glycosylase
      digestion. Slab gel sequence analysis indicated that uracil residues were formed
      at the hot-spot sequence of 5'-(G/C)[A]n = 1,2 (Br)U(Br)U-3' in 302-nm
      irradiation of (Br)U-substituted DNA. Furthermore, we found that the uracil
      residue was also formed at the reverse sequence 5'-(Br)U(Br)U[A]n = 1,2(G/C)-3',
      which suggests that both 5'-(G/C)[A]n = 1,2 (Br)U(Br)U-3' and 5'-(Br)U(Br)U[A]n =
      1,2(G/C)-3' are hot-spot sequences for the formation of the uracil-5-yl radical. 

PMID- 25398905
TI  - Type material in the NCBI Taxonomy Database.
AB  - Type material is the taxonomic device that ties formal names to the physical
      specimens that serve as exemplars for the species. For the prokaryotes these are
      strains submitted to the culture collections; for the eukaryotes they are
      specimens submitted to museums or herbaria. The NCBI Taxonomy Database
      (http://www.ncbi.nlm.nih.gov/taxonomy) now includes annotation of type material
      that we use to flag sequences from type in GenBank and in Genomes. This has
      important implications for many NCBI resources, some of which are outlined below.

PMID- 25398906
TI  - Database resources of the National Center for Biotechnology Information.
AB  - The National Center for Biotechnology Information (NCBI) provides a large suite
      of online resources for biological information and data, including the
      GenBank((r)) nucleic acid sequence database and the PubMed database of citations
      and abstracts for published life science journals. Additional NCBI resources
      focus on literature (Bookshelf, PubMed Central (PMC) and PubReader); medical
      genetics (ClinVar, dbMHC, the Genetic Testing Registry, HIV-1/Human Protein
      Interaction Database and MedGen); genes and genomics (BioProject, BioSample,
      dbSNP, dbVar, Epigenomics, Gene, Gene Expression Omnibus (GEO), Genome,
      HomoloGene, the Map Viewer, Nucleotide, PopSet, Probe, RefSeq, Sequence Read
      Archive, the Taxonomy Browser, Trace Archive and UniGene); and proteins and
      chemicals (Biosystems, COBALT, the Conserved Domain Database (CDD), the Conserved
      Domain Architecture Retrieval Tool (CDART), the Molecular Modeling Database
      (MMDB), Protein Clusters, Protein and the PubChem suite of small molecule
      databases). The Entrez system provides search and retrieval operations for many
      of these databases. Augmenting many of the Web applications are custom
      implementations of the BLAST program optimized to search specialized data sets.
      All of these resources can be accessed through the NCBI home page at
      http://www.ncbi.nlm.nih.gov. 

PMID- 25398907
TI  - Pin1-mediated Sp1 phosphorylation by CDK1 increases Sp1 stability and decreases
      its DNA-binding activity during mitosis.
AB  - We have shown that Sp1 phosphorylation at Thr739 decreases its DNA-binding
      activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is
      necessary, but not sufficient for the inhibition of its DNA-binding activity
      during mitosis. We demonstrated that Pin1 could be recruited to the Thr739(p)-Pro
      motif of Sp1 to modulate the interaction between phospho-Sp1 and CDK1, thereby
      facilitating CDK1-mediated phosphorylation of Sp1 at Ser720, Thr723 and Thr737
      during mitosis. Loss of the C-terminal end of Sp1 (amino acids 741-785)
      significantly increased Sp1 phosphorylation, implying that the C-terminus
      inhibits CDK1-mediated Sp1 phosphorylation. Binding analysis of Sp1 peptides to
      Pin1 by isothermal titration calorimetry indicated that Pin1 interacts with
      Thr739(p)-Sp1 peptide but not with Thr739-Sp1 peptide. X-ray crystallography data
      showed that the Thr739(p)-Sp1 peptide occupies the active site of Pin1. Increased
      Sp1 phosphorylation by CDK1 during mitosis not only stabilized Sp1 levels by
      decreasing interaction with ubiquitin E3-ligase RNF4 but also caused Sp1 to move
      out of the chromosomes completely by decreasing its DNA-binding activity, thereby
      facilitating cell cycle progression. Thus, Pin1-mediated conformational changes
      in the C-terminal region of Sp1 are critical for increased CDK1-mediated Sp1
      phosphorylation to facilitate cell cycle progression during mitosis.

PMID- 25398909
TI  - Fission yeast Cactin restricts telomere transcription and elongation by
      controlling Rap1 levels.
AB  - The telomeric transcriptome comprises multiple long non-coding RNAs generated by
      transcription of linear chromosome ends. In a screening performed in
      Schizosaccharomyces pombe, we identified factors modulating the cellular levels
      of the telomeric transcriptome. Among these factors, Cay1 is the fission yeast
      member of the conserved family of Cactins, uncharacterized proteins crucial for
      cell growth and survival. In cay1? mutants, the cellular levels of the telomeric
      factor Rap1 are drastically diminished due to defects in rap1+ pre-mRNA splicing
      and Rap1 protein stability. cay1? cells accumulate histone H3 acetylated at
      lysine 9 at telomeres, which become transcriptionally desilenced, are over
      elongated by telomerase and cause chromosomal aberrations in the cold.
      Overexpressing Rap1 in cay1+ deleted cells significantly reverts all telomeric
      defects. Additionally, cay1? mutants accumulate unprocessed Tf2 retrotransposon
      RNA through Rap1-independent mechanisms. Thus, Cay1 plays crucial roles in cells
      by ultimately harmonizing expression of transcripts originating from seemingly
      unrelated genomic loci. 

PMID- 25398912
TI  - Abdominal aortic feminism.
AB  - A 79-year-old woman presented to a private medical practice 2 years previously
      for an elective ultrasound screening scan. This imaging provided the evidence for
      a diagnosis of an abdominal aortic aneurysm (AAA) to be made. Despite having a
      number of recognised risk factors for an AAA, her general practitioner at the
      time did not follow the guidance set out by the private medical professional,
      that is, to refer the patient to a vascular specialist to be entered into a
      surveillance programme and surgically evaluated. The patient became symptomatic
      with her AAA, was admitted to hospital and found to have a tender, symptomatic, 6
      cm leaking AAA. She consented for an emergency open AAA repair within a few hours
      of being admitted to hospital, despite the 50% perioperative mortality risk. The
      patient spent 4 days in intensive care where she recovered well. She was
      discharged after a 12 day hospital stay but unfortunately passed away shortly
      after her discharge from a previously undiagnosed gastric cancer.

PMID- 25398910
TI  - GRIM REAPER peptide binds to receptor kinase PRK5 to trigger cell death in
      Arabidopsis.
AB  - Recognition of extracellular peptides by plasma membrane-localized receptor
      proteins is commonly used in signal transduction. In plants, very little is known
      about how extracellular peptides are processed and activated in order to allow
      recognition by receptors. Here, we show that induction of cell death in planta by
      a secreted plant protein GRIM REAPER (GRI) is dependent on the activity of the
      type II metacaspase METACASPASE-9. GRI is cleaved by METACASPASE-9 in vitro
      resulting in the release of an 11 amino acid peptide. This peptide bound in vivo
      to the extracellular domain of the plasma membrane-localized, atypical leucine
      rich repeat receptor-like kinase POLLEN-SPECIFIC RECEPTOR-LIKE KINASE 5 (PRK5)
      and was sufficient to induce oxidative stress/ROS-dependent cell death. This
      shows a signaling pathway in plants from processing and activation of an
      extracellular protein to recognition by its receptor. 

PMID- 25398911
TI  - Dusp5 negatively regulates IL-33-mediated eosinophil survival and function.
AB  - Mitogen-activated protein kinase (MAPK) activation controls diverse cellular
      functions including cellular survival, proliferation, and apoptosis. Tuning of
      MAPK activation is counter-regulated by a family of dual-specificity phosphatases
      (DUSPs). IL-33 is a recently described cytokine that initiates Th2 immune
      responses through binding to a heterodimeric IL-33Ralpha (ST2L)/IL-1alpha
      accessory protein (IL-1RAcP) receptor that coordinates activation of ERK and NF
      kappaB pathways. We demonstrate here that DUSP5 is expressed in eosinophils, is
      upregulated following IL-33 stimulation and regulates IL-33 signaling. Dusp5(-/-)
      mice have prolonged eosinophil survival and enhanced eosinophil effector
      functions following infection with the helminth Nippostrongylus brasiliensis. IL
      33-activated Dusp5(-/-) eosinophils exhibit increased cellular ERK1/2 activation
      and BCL-XL expression that results in enhanced eosinophil survival. In addition,
      Dusp5(-/-) eosinophils demonstrate enhanced IL-33-mediated activation and
      effector functions. Together, these data support a role for DUSP5 as a novel
      negative regulator of IL-33-dependent eosinophil function and survival. 

PMID- 25398913
TI  - When the going gets rough: a sequela of splenic trauma.

PMID- 25398914
TI  - Traumatic intracranial aneurysm after penetrating brain trauma.

PMID- 25398915
TI  - Disseminated Cladophialophora bantiana disease in a patient with prediabetes.
AB  - Cladophialophora bantiana, a dematiaceous fungus from the family
      Phaeohyphomycetes, is highly neurotropic and primarily reported as a rare cause
      of brain abscess. Pulmonary infection and disease outside the central nervous
      system is extremely rare, particularly in immunocompetent patients. We report an
      unusual case of disseminated cladosporiosis in a young man with a new diagnosis
      of prediabetes but no other identifiable risk factors for disease. Fungal
      cultures were positive for C. bantiana from brain abscess aspiration, vertebral
      bone cultures and subcarinal lymph node biopsy. Although the patient demonstrated
      initial good response to surgical debridement of brain abscesses plus antifungal
      therapy, he eventually expired from septic shock secondary to C. bantiana
      pneumonia and recurrent brain abscesses 2 years after initial diagnosis.

PMID- 25398916
TI  - Adnexal mass secondary to extranodal marginal zone lymphoma of mucosa-associated
      lymphoid tissue (MALT lymphoma) with associated amyloid deposition.
AB  - Systemic amyloid light chain amyloidosis (AL amyloidosis) is usually seen in
      association with a plasma cell disorder. Amyloid deposition associated with
      extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT
      lymphoma) is a rare phenomenon that is not typically associated with systemic AL
      amyloidosis. We describe the unusual case of a patient with an adnexal mass
      secondary to MALT lymphoma with associated amyloid deposition. 

PMID- 25398917
TI  - Unusual case of acute tracheal injury complicated by application of positive end
      expiratory pressure (PEEP).
AB  - Blunt neck trauma can be caused by a variety of injuries such as deceleration,
      road traffic accidents and crush injuries. The worst scenario is airway rupture.
      We report an unusual case of acute tracheal injury in a 34-year-old Irish man who
      presented with a history of strangulation while working with a tractor. On
      arrival, he had one episode of mild haemoptysis and reported pain around the base
      of the neck and voice hoarseness. His chest X-ray revealed pneumopericardium and
      CT of thorax showed airway oedema. After elective intubation, positive end
      expiratory pressure (PEEP) of 5 cm H2O caused deterioration in his clinical
      condition with increasing surgical emphysema and rise of carbon dioxide partial
      pressure (PaCO2), which was completely reversed after stopping PEEP. This case
      shows how PEEP and intermittent positive pressure ventilation can worsen air leak
      and compromise stability in patients with acute tracheal injury.

PMID- 25398918
TI  - Lingual thyroid associated with hypothyroidism as a cause for short stature.

PMID- 25398919
TI  - BALToma masquerading as pulmonary tuberculosis.
AB  - A 53-year-old man with a significant smoking history presented with chronic
      cough, exertional breathlessness, intermittent fever, weight loss and anorexia. A
      review of his past medical records revealed he was diagnosed to have sputum smear
      positive pulmonary tuberculosis 5 years earlier, for which he had received
      multiple courses of incomplete antitubercular therapy. This time, though he was
      primarily suspected to have active pulmonary tuberculosis, lack of
      microbiological evidence and further investigations including histopathological
      evaluation of lung lesions confirmed a diagnosis of Marginal zone B cell lymphoma
      of mucosa-associated lymphoid tissue (MALToma/BALToma). The patient was managed
      with radical radiation therapy to which he responded well.

PMID- 25398920
TI  - Malignant caeco-sigmoid fistula.

PMID- 25398921
TI  - Blood, sweat and tears: androgenic-anabolic steroid misuse and recurrent primary
      post-tonsillectomy haemorrhage.
AB  - A 30-year-old male body builder and androgenic-anabolic steroid and insulin
      abuser was admitted for day case elective tonsillectomy (bipolar). He returned
      with primary post-tonsillectomy haemorrhage 18 h after the operation and required
      bipolar cautery to the multiple small bleeding points in the right and left
      tonsillar fossa. Thorough coagulation screen was normal. Recurrent primary
      haemorrhage occurred 3 h post-operatively requiring immediate surgical
      intervention, removal of the inferior poles, precautionary throat packs,
      intubation and observation on the intensive treatment unit (ITU). Re-examination
      in theatre revealed a bleeding left superior pole that was under-run to achieve
      haemostasis and the patient returned to ITU. Hypertensive episodes were noted in
      the emergency department and intraoperatively including one recording >200 mm Hg.
      Haemostasis was eventually achieved once the blood pressure was adequately
      controlled. A slow wean of steroids was also instigated and the patient was
      managed on a surgical ward for 2 weeks post-tonsillectomy.

PMID- 25398922
TI  - Brown tumours: widespread involvement of multiple maxillofacial bones and
      cervical spine.

PMID- 25398923
TI  - Sinking skin flap syndrome in glioblastoma.
AB  - Sinking skin flap syndrome (SSFS) is a rare neurological complication in patients
      with traumatic haemorrhage, stroke or cerebral oedema who undergo decompressive
      craniectomy to relieve increased intracranial pressure. Hallmark of SSFS is the
      sinking of the scalp to a plane lower than the edges of the skull defect in the
      setting of neurological deterioration. Our objective is to report that SSFS can
      present after small craniotomy without cerebral cortex compression and to share
      our diagnostic/therapeutic approach. A 62-year-old woman with a glioblastoma
      developed SSFS after a small craniectomy and tumour resection without cerebral
      cortex compression but a decrease in the surgical cavity volume. Brain MRI showed
      decreased size of the surgical cavity. Interestingly, the patient also developed
      posterior reversible encephalopathy syndrome (PRES). This case highlights an
      atypical presentation of SSFS and the possible association with PRES. It also
      illustrates how an early cranioplasty can successfully reverse SSFS. 

PMID- 25398924
TI  - Spontaneous choledochal cyst perforation in pregnancy with co-existent chronic
      pancreatitis.
AB  - Choledochal cysts are a congenital disorder of the bile duct, usually presenting
      in childhood. As they cause weakening of the wall of the bile duct, any distal
      obstruction, infection or reflux of amylase-rich fluid in the biliary tract can
      predispose to spontaneous perforation. A 25-year-old pregnant woman at 35 weeks
      of gestation presented with acute abdominal and fetal distress. On emergency
      laparotomy, common bile duct perforations were detected. T-tube drainage and
      caesarean section were performed. A t-tube cholangiogram revealed the diagnosis
      of a choledochal cyst with an abnormal pancreatobiliary junction and chronic
      pancreatitis. The patient later underwent cyst excision with Roux en Y
      hepaticojejunostomy. Spontaneous choledochal cyst perforation in pregnancy can be
      successfully managed by a two-stage operation.

PMID- 25398925
TI  - Pulmonary co-infection with Nocardia and Aspergillus in a patient with adult
      onset Still's disease receiving steroids and tacrolimus.
AB  - Patients on immunosuppression are at risk of unusual infections. We present a man
      diagnosed to have adult-onset Still's disease who, on high-dose oral steroid and
      tacrolimus, developed a cavitating pneumonia due to co-infection with Aspergillus
      flavus and Nocardia. Timely diagnosis and institution of appropriate therapy
      resulted in a favourable clinical outcome. Such co-infection in a patient
      receiving tacrolimus is rare in the published literature. This case serves to
      emphasise the need to be vigilant for unusual infections in patients who are
      immunosuppressed, either due to drugs or underlying disease condition. 

PMID- 25398926
TI  - Biology, detection, and clinical implications of circulating tumor cells.
AB  - Cancer metastasis is the main cause of cancer-related death, and dissemination of
      tumor cells through the blood circulation is an important intermediate step that
      also exemplifies the switch from localized to systemic disease. Early detection
      and characterization of circulating tumor cells (CTCs) is therefore important as
      a general strategy to monitor and prevent the development of overt metastatic
      disease. Furthermore, sequential analysis of CTCs can provide clinically relevant
      information on the effectiveness and progression of systemic therapies (e.g.,
      chemo-, hormonal, or targeted therapies with antibodies or small inhibitors).
      Although many advances have been made regarding the detection and molecular
      characterization of CTCs, several challenges still exist that limit the current
      use of this important diagnostic approach. In this review, we discuss the biology
      of tumor cell dissemination, technical advances, as well as the challenges and
      potential clinical implications of CTC detection and characterization. 

PMID- 25398933
TI  - How we treat chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) remains a common and potentially life
      threatening complication of allogeneic hematopoietic stem cell transplantation
      (HCT). The 2-year cumulative incidence of chronic GVHD requiring systemic
      treatment is ~30% to 40% by National Institutes of Health criteria. The risk of
      chronic GVHD is higher and the duration of treatment is longer after HCT with
      mobilized blood cells than with marrow cells. Clinical manifestations can impair
      activities of daily living and often linger for years. Hematology and oncology
      specialists who refer patients to centers for HCT are often subsequently involved
      in the management of chronic GVHD when patients return to their care after HCT.
      Treatment of these patients can be optimized under shared care arrangements that
      enable referring physicians to manage long-term administration of
      immunosuppressive medications and supportive care with guidance from transplant
      center experts. Keys to successful collaborative management include early
      recognition in making the diagnosis of chronic GVHD, comprehensive evaluation at
      the onset and periodically during the course of the disease, prompt institution
      of systemic and topical treatment, appropriate monitoring of the response,
      calibration of treatment intensity over time in order to avoid overtreatment or
      undertreatment, and the use of supportive care to prevent complications and
      disability.

PMID- 25398934
TI  - Risk of venous and arterial thrombotic events in patients diagnosed with
      superficial vein thrombosis: a nationwide cohort study.
AB  - Recently, it has become apparent that superficial vein thrombosis (SVT) can have
      serious complications. However, the magnitude of the risk of subsequent deep
      venous and arterial thrombotic events remains unknown. We examined this in a
      nationwide population-based setting during a period when SVT was not treated
      routinely with anticoagulants. The Danish National Registry of Patients, covering
      all Danish hospitals, was used to identify 10 973 patients with a first-time
      diagnosis of SVT between 1980 and 2012. A comparison cohort of 515 067 subjects,
      matched by age, gender, and calendar year, was selected from the general Danish
      population. Outcomes were venous thromboembolism, acute myocardial infarction,
      ischemic stroke, and death. During median follow-up of 7 years, the incidence
      rate of venous thromboembolism was 18.0/1000 person-years (95% confidence
      interval [CI], 17.2-18.9). The highest risk occurred in the first 3 months (3.4%;
      95% CI, 3.0-3.7). Compared with the general population, the hazard ratio was 71.4
      (95% CI, 60.2-84.7) in this period, steadily decreasing to 5.1 (95% CI 4.6-5.5),
      5 years after the SVT. The hazard ratios for acute myocardial infarction, stroke,
      and death were 1.2 (95% CI, 1.1-1.3), 1.3 (95% CI, 1.2-1.4), and 1.3 (95% CI, 1.2
      1.3), respectively, with the highest risk also shortly after SVT. These data
      indicate the prognostic importance of SVT and may form the basis for clinical
      decision-making regarding anticoagulation. 

PMID- 25398935
TI  - Phase 2 study of carfilzomib, thalidomide, and dexamethasone as
      induction/consolidation therapy for newly diagnosed multiple myeloma.
AB  - This multicenter phase 2 study of the European Myeloma Network investigated the
      combination of carfilzomib, thalidomide, and dexamethasone (KTd) as
      induction/consolidation therapy for transplant-eligible patients with previously
      untreated multiple myeloma (N = 91). During KTd induction therapy, patients
      received 4 cycles of carfilzomib 20/27 mg/m(2) (n = 50), 20/36 mg/m(2) (n = 20),
      20/45 mg/m(2) (n = 21), or 20/56 mg/m(2) (n = 20) on days 1, 2, 8, 9, 15, and 16
      of a 28-day cycle; thalidomide 200 mg on days 1 to 28; and dexamethasone 20 mg on
      days 1, 2, 8, 9, 15, and 16. After autologous stem cell transplantation, patients
      proceeded to KTd consolidation therapy, where the target doses of carfilzomib
      were 27 mg/m(2), 36 mg/m(2), 45 mg/m(2), or 56 mg/m(2), respectively, and
      thalidomide 50 mg. Common grade 3/4 adverse events included respiratory (15%),
      gastrointestinal (12%), and skin disorders (10%); polyneuropathy was infrequent
      (1%). Complete response rates after induction and consolidation treatment were
      25% and 63%, respectively; rates of very good partial response or better after
      induction and consolidation were 68% and 89%, respectively. At a median follow-up
      of 23 months, the 36-month progression-free survival rate was 72%. The KTd
      induction and consolidation regimens were active, safe, and well tolerated. This
      study was registered at http://www.trialregister.nl as #NTR2422. 

PMID- 25398936
TI  - Transcription factor IRF8 plays a critical role in the development of murine
      basophils and mast cells.
AB  - Basophils and mast cells play critical roles in host defense against pathogens
      and allergic disorders. However, the molecular mechanism by which these cells are
      generated is not completely understood. Here we demonstrate that interferon
      regulatory factor-8 (IRF8), a transcription factor essential for the development
      of several myeloid lineages, also regulates basophil and mast cell development.
      Irf8(-/-) mice displayed a severe reduction in basophil counts, which was
      accounted for by the absence of pre-basophil and mast cell progenitors (pre
      BMPs). Although Irf8(-/-) mice retained peripheral tissue mast cells, remaining
      progenitors from Irf8(-/-) mice including granulocyte progenitors (GPs) were
      unable to efficiently generate either basophils or mast cells, indicating that
      IRF8 also contributes to the development of mast cells. IRF8 appeared to function
      at the GP stage, because IRF8 was expressed in GPs, but not in basophils, mast
      cells, and basophil/mast cell-restricted progenitor cells. Furthermore, we
      demonstrate that GATA2, a transcription factor known to promote basophil and mast
      cell differentiation, acts downstream of IRF8. These results shed light on the
      pathways and mechanism underlying the development of basophils and mast cells. 

PMID- 25398937
TI  - Platelet PI3Kbeta and GSK3 regulate thrombus stability at a high shear rate.
AB  - Class IA phosphoinositide 3-kinase beta (PI3Kbeta) is considered a potential drug
      target in arterial thrombosis, which is a major cause of death worldwide. Here we
      show that a striking phenotype of mice with selective p110beta deletion in the
      megakaryocyte lineage is thrombus instability at a high shear rate, which is an
      effect that is not detected in the absence of p110alpha in platelets. The high
      shear rate-dependent thrombus instability in the absence of p110beta is observed
      both ex vivo and in vivo with the formation of platelet emboli. Moreover,
      PI3Kbeta is required for the recruitment of new platelets to a growing thrombus
      when a pathological high shear is applied. Treatment of human blood with AZD6482,
      a selective PI3Kbeta inhibitor, phenocopies p110beta deletion in mouse platelets,
      which highlights the role of the kinase activity of p110beta. Within the growing
      platelet thrombus, p110beta inactivation impairs the activating phosphorylations
      of Akt and the inhibitory phosphorylation of GSK3. In accord with these data,
      pharmacologic inhibition of GSK3 restores thrombus stability. Thus, platelet
      PI3Kbeta is not essential for thrombus growth and stability at normal arterial
      shear but has a specific and critical role in maintaining the integrity of the
      formed thrombus on elevation of shear rate, suggesting a potential risk of
      embolization on treatment with PI3Kbeta inhibitors. 

PMID- 25398938
TI  - Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and
      responds to EZH2 inhibition.
AB  - Acute myeloid leukemia (AML) is associated with deregulation of DNA methylation;
      however, many cases do not bear mutations in known regulators of cytosine guanine
      dinucleotide (CpG) methylation. We found that mutations in WT1, IDH2, and CEBPA
      were strongly linked to DNA hypermethylation in AML using a novel integrative
      analysis of The Cancer Genome Atlas data based on Boolean implications, if-then
      rules that identify all individual CpG sites that are hypermethylated in the
      presence of a mutation. Introduction of mutant WT1 (WT1mut) into wild-type AML
      cells induced DNA hypermethylation, confirming mutant WT1 to be causally
      associated with DNA hypermethylation. Methylated genes in WT1mut primary patient
      samples were highly enriched for polycomb repressor complex 2 (PRC2) targets,
      implicating PRC2 dysregulation in WT1mut leukemogenesis. We found that PRC2
      target genes were aberrantly repressed in WT1mut AML, and that expression of
      mutant WT1 in CD34(+) cord blood cells induced myeloid differentiation block.
      Treatment of WT1mut AML cells with short hairpin RNA or pharmacologic
      PRC2/enhancer of zeste homolog 2 (EZH2) inhibitors promoted myeloid
      differentiation, suggesting EZH2 inhibitors may be active in this AML subtype.
      Our results highlight a strong association between mutant WT1 and DNA
      hypermethylation in AML and demonstrate that Boolean implications can be used to
      decipher mutation-specific methylation patterns that may lead to therapeutic
      insights. 

PMID- 25398939
TI  - Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2
      hydroxyglutarate in Drosophila.
AB  - Gain-of-function mutations in nicotinamide adenine dinucleotide phosphate
      dependent isocitrate dehydrogenase (IDH)1 and IDH2 frequently arise in human
      leukemias and other cancers and produce high levels of D-2-hydroxyglutarate (D
      2HG). We expressed the R195H mutant of Drosophila Idh (CG7176), which is
      equivalent to the human cancer-associated IDH1-R132H mutant, in fly tissues using
      the UAS-Gal4 binary expression system. Idh-R195H caused a >25-fold elevation of D
      2HG when expressed ubiquitously in flies. Expression of mutant Idh in larval
      blood cells (hemocytes) resulted in higher numbers of circulating blood cells.
      Mutant Idh expression in fly neurons resulted in neurologic and wing-expansion
      defects, and these phenotypes were rescued by genetic modulation of superoxide
      dismutase 2, p53, and apoptotic caspase cascade mediators. Idh-R163Q, which is
      homologous to the common leukemia-associated IDH2-R140Q mutant, resulted in
      moderately elevated D-2HG and milder phenotypes. We identified the fly homolog of
      D-2-hydroxyglutaric acid dehydrogenase (CG3835), which metabolizes D-2HG, and
      showed that coexpression of this enzyme with mutant Idh abolishes mutant Idh
      associated phenotypes. These results provide a flexible model system to
      interrogate a cancer-related genetic and metabolic pathway and offer insights
      into the impact of IDH mutation and D-2HG on metazoan tissues. 

PMID- 25398940
TI  - IDH2 mutation-induced histone and DNA hypermethylation is progressively reversed
      by small-molecule inhibition.
AB  - Mutations of IDH1 and IDH2, which produce the oncometabolite 2-hydroxyglutarate
      (2HG), have been identified in several tumors, including acute myeloid leukemia.
      Recent studies have shown that expression of the IDH mutant enzymes results in
      high levels of 2HG and a block in cellular differentiation that can be reversed
      with IDH mutant-specific small-molecule inhibitors. To further understand the
      role of IDH mutations in cancer, we conducted mechanistic studies in the TF-1
      IDH2 R140Q erythroleukemia model system and found that IDH2 mutant expression
      caused both histone and genomic DNA methylation changes that can be reversed when
      IDH2 mutant activity is inhibited. Specifically, histone hypermethylation is
      rapidly reversed within days, whereas reversal of DNA hypermethylation proceeds
      in a progressive manner over the course of weeks. We identified several gene
      signatures implicated in tumorigenesis of leukemia and lymphoma, indicating a
      selective modulation of relevant cancer genes by IDH mutations. As methylation of
      DNA and histones is closely linked to mRNA expression and differentiation, these
      results indicate that IDH2 mutant inhibition may function as a cancer therapy via
      histone and DNA demethylation at genes involved in differentiation and
      tumorigenesis. 

PMID- 25398942
TI  - Response to "Tumor cells in search for glutamate: an alternative explanation for
      increased invasiveness of IDH1 mutant gliomas".

PMID- 25398943
TI  - Disruption of the nuclear membrane by perinuclear inclusions of mutant huntingtin
      causes cell-cycle re-entry and striatal cell death in mouse and cell models of
      Huntington's disease.
AB  - Accumulation of N-terminal fragments of mutant huntingtin (mHTT) in the
      cytoplasm, nuclei and axons of neurons is a hallmark of Huntington's disease
      (HD), although how these fragments negatively impact neurons remains unclear. We
      followed the distribution of mHTT in the striata of transgenic R6/2-J2 HD mice as
      their motor function declined. The fraction of cells with diffuse, perinuclear or
      intranuclear mHTT changed in parallel with decreasing motor function. In
      transgenic mice, medium spiny neurons (MSNs) that exhibited perinuclear
      inclusions expressed cell-cycle markers typically not seen in the striata of
      normal mice, and these cells are preferentially lost as disease progresses.
      Electron microscopy reveals that perinuclear inclusions disrupt the nuclear
      envelope. The progression of perinuclear inclusions being accompanied by cell
      cycle activation and culminating in cell death was also observed in 1 degrees 
      cortical neurons. These observations provide a strong correlation between the
      subcellular location of mHTT, disruption of the nucleus, re-entry into the cell
      cycle and eventual neuronal death. They also highlight the fact that the
      subcellular distribution of mHTT is highly dynamic such that the distribution of
      mHTT observed depends greatly on the stage of the disease being examined. 

PMID- 25398944
TI  - CNV instability associated with DNA replication dynamics: evidence for
      replicative mechanisms in CNV mutagenesis.
AB  - Copy number variation (CNV) in the human genome is of vital importance to human
      health and evolution of our species. However, much of the molecular basis of CNV
      mutagenesis remains to be elucidated. Considering the DNA replication model of
      'fork stalling and template switching' for CNV formation, we hypothesized that
      replication fork progression could be important for CNV mutagenesis. However,
      molecular assays of replication fork progression at the genome level are
      technically challenging. Instead, we conducted an estimation of DNA replication
      dynamics, as the statistic R, using the readily available data of replication
      timing. Small R-values can reflect 'slowed' replication, which could result from
      less fork initiation, reduced fork speed or fork barriers. We generated genome
      wide profiles of R in the genomes of human, mouse and Drosophila. Intriguingly,
      the CNV breakpoints in all three genomes showed significantly biased
      distributions toward the genomic regions with small R-values, suggesting
      potential replication stress-induced CNV instability. Notably, among the human
      CNVs with distinct breakpoint junction characteristics, the homology-mediated and
      VNTR-mediated CNVs contribute the most to the correlation between CNV instability
      and the statistic R, consistent with the recent findings in the C. elegans and
      yeast genomes of repeat-induced DNA replication error and consequent CNV
      formation. The statistic R may reflect both replication stress and the effect of
      local genome architecture on fork progression. Our concordant observations
      suggest an important role for DNA replicative mechanisms in CNV mutagenesis and
      genome instability. 

PMID- 25398946
TI  - Evidence of a link between ubiquilin 2 and optineurin in amyotrophic lateral
      sclerosis.
AB  - A mutation in the ubiquilin 2 gene (UBQLN2) was recently identified as a cause of
      X-linked amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) and a
      major component of the inclusion bodies commonly found with a wide variety of
      ALS. ALS-linked mutations in UBQLN2 are clustered in a unique proline-X-X repeat
      region, reportedly leading to impairment of the ubiquitin proteasome system.
      However, the molecular properties of mutant UBQLN2 remain unclear. To gain
      insight into the pathogenesis of UBQLN2-linked ALS/FTD, we examined the
      biochemical and cellular characteristics of mutant UBQLN2 in vitro. UBQLN2
      localized in Rab11-positive endosomal vesicles formed by the ALS-linked molecule
      optineurin (OPTN). These vesicles were ubiquitin- and p62-immunopositive and also
      co-localized with an initiator of the autophagic process, ULK1, after amino acid
      starvation. An ALS-linked mutation (E478G) in OPTN abolished vesicle formation.
      ALS-linked mutations in UBQLN2 additively enhanced UBQLN2 aggregation and
      formation of inclusion bodies, resulting in mislocation from OPTN vesicles.
      UBQLN2 was found to be a potent regulator of the levels of the FTD-linked
      secretory factor progranulin, possibly via the endosomal system, and ALS-linked
      mutations disturbed these functional consequences. This study demonstrates that
      ALS-linked mutations in both OPTN and UBQLN2 interfere with the constitution of
      specific endosomal vesicles, suggesting that the vesicles are involved in protein
      homeostasis and that these proteins function in common pathological processes.
      These data suggest a novel disease spectrum and provide new pathological insights
      into OPTN and UBQLN2, enhancing our understanding of the molecular basis of
      ALS/FTD. 

PMID- 25398945
TI  - Spata7 is a retinal ciliopathy gene critical for correct RPGRIP1 localization and
      protein trafficking in the retina.
AB  - Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP) are
      severe hereditary diseases that causes visual impairment in infants and children.
      SPATA7 has recently been identified as the LCA3 and juvenile RP gene in humans,
      whose function in the retina remains elusive. Here, we show that SPATA7 localizes
      at the primary cilium of cells and at the connecting cilium (CC) of photoreceptor
      cells, indicating that SPATA7 is a ciliary protein. In addition, SPATA7 directly
      interacts with the retinitis pigmentosa GTPase regulator interacting protein 1
      (RPGRIP1), a key connecting cilium protein that has also been linked to LCA. In
      the retina of Spata7 null mutant mice, a substantial reduction of RPGRIP1 levels
      at the CC of photoreceptor cells is observed, suggesting that SPATA7 is required
      for the stable assembly and localization of the ciliary RPGRIP1 protein complex.
      Furthermore, our results pinpoint a role of this complex in protein trafficking
      across the CC to the outer segments, as we identified that rhodopsin accumulates
      in the inner segments and around the nucleus of photoreceptors. This accumulation
      then likely triggers the apoptosis of rod photoreceptors that was observed. Loss
      of Spata7 function in mice indeed results in a juvenile RP-like phenotype,
      characterized by progressive degeneration of photoreceptor cells and a strongly
      decreased light response. Together, these results indicate that SPATA7 functions
      as a key member of a retinal ciliopathy-associated protein complex, and that
      apoptosis of rod photoreceptor cells triggered by protein mislocalization is
      likely the mechanism of disease progression in LCA3/ juvenile RP patients. 

PMID- 25398948
TI  - Characterization of the dipeptide repeat protein in the molecular pathogenesis of
      c9FTD/ALS.
AB  - The expansion of the GGGGCC hexanucleotide repeat in the non-coding region of the
      chromosome 9 open-reading frame 72 (C9orf72) gene is the most common cause of
      frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS)
      (c9FTD/ALS). Recently, it was reported that an unconventional mechanism of repeat
      associated non-ATG (RAN) translation arises from C9orf72 expansion. Sense and
      anti-sense transcripts of the expanded C9orf72 repeat, i.e. the dipeptide repeat
      protein (DRP) of glycine-alanine (poly-GA), glycine-proline (poly-GP), glycine
      arginine (poly-GR), proline-arginine (poly-PR) and proline-alanine (poly-PA), are
      deposited in the brains of patients with c9FTD/ALS. However, the pathological
      significance of RAN-translated peptides remains unknown. We generated synthetic
      cDNAs encoding 100 repeats of DRP without a GGGGCC repeat and evaluated the
      effects of these proteins on cultured cells and cortical neurons in vivo. Our
      results revealed that the poly-GA protein formed highly aggregated ubiquitin/p62
      positive inclusion bodies in neuronal cells. In contrast, the highly basic
      proteins poly-GR and PR also formed unique ubiquitin/p62-negative cytoplasmic
      inclusions, which co-localized with the components of RNA granules. The
      evaluation of cytotoxicity revealed that overexpressed poly-GA, poly-GP and poly
      GR increased the substrates of the ubiquitin-proteasome system (UPS), including
      TDP-43, and enhanced the sensitivity to a proteasome inhibitor, indicating that
      these DRPs are cytotoxic, possibly via UPS dysfunction. The present data indicate
      that a gain-of-function mechanism of toxic DRPs possibly contributes to
      pathogenesis in c9FTD/ALS and that DRPs may serve as novel therapeutic targets in
      c9FTD/ALS. 

PMID- 25398947
TI  - Evidence of non-pancreatic beta cell-dependent roles of Tcf7l2 in the regulation
      of glucose metabolism in mice.
AB  - Non-coding variation within TCF7L2 remains the strongest genetic determinant of
      type 2 diabetes risk in humans. A considerable effort has been placed in
      understanding the functional roles of TCF7L2 in pancreatic beta cells, despite
      evidence of TCF7L2 expression in various peripheral tissues important in glucose
      homeostasis. Here, we use a humanized mouse model overexpressing Tcf7l2,
      resulting in glucose intolerance, to infer the contribution of Tcf7l2
      overexpression in beta cells and in other tissues to the metabolic phenotypes
      displayed by these mice. Restoring Tcf7l2 expression specifically in beta cells
      to endogenous levels, in face of its overexpression elsewhere, results in
      impaired insulin secretion, reduced beta cell number and islet area,
      corroborating data obtained in humans showing similar phenotypes as a result of
      manipulations leading to Tcf7l2 loss of function. Interestingly, the persistent
      overexpression of Tcf7l2 in non-pancreatic tissues results in a significant
      worsening in glucose tolerance in vivo, indicating that Tcf7l2 overexpression in
      beta cells does not account for the glucose intolerance in the Tcf7l2
      overexpression mouse model. Collectively, these data posit that Tcf7l2 plays key
      roles in glucose metabolism through actions beyond pancreatic beta cells, and
      further points to functionally opposing cell-type specific effects for Tcf7l2 on
      the maintenance of balanced glucose metabolism, thereby urging a careful
      examination of its role in non-pancreatic tissues as well as its composite
      metabolic effects across distinct tissues. Uncovering these roles may lead to new
      therapeutic targets for type 2 diabetes. 

PMID- 25398949
TI  - Loss of the thyroid hormone-binding protein Crym renders striatal neurons more
      vulnerable to mutant huntingtin in Huntington's disease.
AB  - The mechanisms underlying preferential atrophy of the striatum in Huntington's
      disease (HD) are unknown. One hypothesis is that a set of gene products
      preferentially expressed in the striatum could determine the particular
      vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied
      the striatal protein u-crystallin (Crym). Crym is the NADPH-dependent p38
      cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH)
      T3 (3,5,3'-triiodo-l-thyronine) transportation. It has been also recently
      identified as the enzyme that reduces the sulfur-containing cyclic ketimines,
      which are potential neurotransmitters. Here, we confirm the preferential
      expression of the Crym protein in the rodent and macaque striatum. Crym
      expression was found to be higher in the macaque caudate than in the putamen.
      Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of
      HD before onset of striatal atrophy. We show that overexpression of Crym in
      striatal medium-size spiny neurons using a lentiviral-based strategy in mice is
      neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in
      vivo. Thus, reduction of Crym expression in HD could render striatal neurons more
      susceptible to mHtt suggesting that Crym may be a key determinant of the
      vulnerability of the striatum. In addition our work points to Crym as a potential
      molecular link between striatal degeneration and the THs deregulation reported in
      HD patients. 

PMID- 25398950
TI  - Intermediate filament protein accumulation in motor neurons derived from giant
      axonal neuropathy iPSCs rescued by restoration of gigaxonin.
AB  - Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused
      by autosomal recessive mutations in the GAN gene resulting in a loss of a
      ubiquitously expressed protein, gigaxonin. Gene replacement therapy is a
      promising strategy for treatment of the disease; however, the effectiveness and
      safety of gigaxonin reintroduction have not been tested in human GAN nerve cells.
      Here we report the derivation of induced pluripotent stem cells (iPSCs) from
      three GAN patients with different GAN mutations. Motor neurons differentiated
      from GAN iPSCs exhibit accumulation of neurofilament (NF-L) and peripherin (PRPH)
      protein and formation of PRPH aggregates, the key pathological phenotypes
      observed in patients. Introduction of gigaxonin either using a lentiviral vector
      or as a stable transgene resulted in normalization of NEFL and PRPH levels in GAN
      neurons and disappearance of PRPH aggregates. Importantly, overexpression of
      gigaxonin had no adverse effect on survival of GAN neurons, supporting the
      feasibility of gene replacement therapy. Our findings demonstrate that GAN iPSCs
      provide a novel model for studying human GAN neuropathologies and for the
      development and testing of new therapies in relevant cell types. 

PMID- 25398951
TI  - Intake of toxic and carcinogenic volatile organic compounds from secondhand smoke
      in motor vehicles.
AB  - BACKGROUND: Volatile organic compounds (VOC) from tobacco smoke are associated
      with cancer, cardiovascular, and respiratory diseases. The objective of this
      study was to characterize the exposure of nonsmokers to VOCs from secondhand
      smoke (SHS) in vehicles using mercapturic acid metabolites. METHODS: Fourteen
      nonsmokers were individually exposed in the backseat to one hour of SHS from a
      smoker seated in the driver's seat who smoked three cigarettes at 20-minute
      intervals in a stationary car with windows opened by 10 cm. Baseline and 0- to 8
      hour postexposure mercapturic acid metabolites of nine VOCs were measured in
      urine. Air-to-urine VOC ratios were estimated on the basis of respirable
      particulate matter (PM2.5) or air nicotine concentration, and lifetime excess
      risk (LER) of cancer death from exposure to acrylonitrile, benzene, and 1,3
      butadiene was estimated for adults. RESULTS: The greatest increase in 0- to 8
      hour postexposure concentrations of mercapturic acids from baseline was MHBMA-3
      (parent, 1,3-butadiene; 2.1-fold), then CNEMA (acrylonitrile; 1.7-fold), PMA
      (benzene; 1.6-fold), MMA (methylating agents; 1.6-fold), and HEMA (ethylene
      oxide; 1.3-fold). The LER of cancer death from exposure to acrylonitrile,
      benzene, and 1,3-butadiene in SHS for 5 hours a week ranged from 15.5 * 10(-6) to
      28.1 * 10(-6) for adults, using air nicotine and PM2.5 to predict air VOC
      exposure, respectively. CONCLUSION: Nonsmokers have significant intake of
      multiple VOCs from breathing SHS in cars, corresponding to health risks that
      exceed the acceptable level. IMPACT: Smoking in cars may be associated with
      increased risks of cancer, respiratory, and cardiovascular diseases among
      nonsmokers.

PMID- 25398952
TI  - Rapid Monitoring and Determination of Class 1 Residual Solvents in
      Pharmaceuticals Using Dispersive Liquid-Liquid Microextraction and Gas
      Chromatography-Mass Spectrometry.
AB  - A simple and rapid dispersive liquid-liquid microextraction (DLLME) method
      coupled with gas chromatography-mass spectrometry (GC-MS) for monitoring and
      determination of class 1 residual solvents, benzene (Bz), carbon tetrachloride
      (CT), 1,2-dichloroethane (1,2-DCE), 1,1-dichloroethene (1,1-DCE), 1,1,1
      trichloroethane (1,1,1-TCE), in pharmaceuticals was developed and evaluated. The
      parameters affecting the extraction efficiency of analytes such as type and
      volume of extraction solvent, type and volume of dispersive solvent and ionic
      strength were investigated and optimized. 1-Octanol and methanol proved to be the
      most suitable extraction and dispersive solvents, respectively. The method showed
      linearity for 1,1-DCE, 1,1,1-TCE, CT, Bz and 1,2-DCE in the ranges of 0.001-80,
      0.005-80, 0.002-80, 0.0001-40 and 0.001-80 ug/mL, respectively. The relative
      recoveries were in the range of 84-92, 87-98, 83-94, 89-98 and 87-96% for 1,1
      DCE, 1,1,1-TCE, CT, Bz and 1,2-DCE, respectively. The obtained results showed
      that the proposed method can be used to monitor and determine class 1 residual
      solvents in pharmaceuticals. 

PMID- 25398953
TI  - Aiming for ideal care: a proposed framework for cancer quality improvement.

PMID- 25398954
TI  - Fifty years of tobacco control: is the glass half full or half empty?

PMID- 25398955
TI  - Payment for oncolytics in the United States: a history of buy and bill and
      proposals for reform.

PMID- 25398956
TI  - Welcoming the era of quality improvement in neuro-oncology.

PMID- 25398957
TI  - Avoiding risky business: supporting optimal home medication administration for
      children with cancer.

PMID- 25398958
TI  - A call to quality in action.

PMID- 25398959
TI  - The National Practice Benchmark for oncology, 2014 report on 2013 data.
AB  - The National Practice Benchmark (NPB) is a unique tool to measure oncology
      practices against others across the country in a way that allows meaningful
      comparisons despite differences in practice size or setting. In today's economic
      environment every oncology practice, regardless of business structure or
      affiliation, should be able to produce, monitor, and benchmark basic metrics to
      meet current business pressures for increased efficiency and efficacy of care.
      Although we recognize that the NPB survey results do not capture the experience
      of all oncology practices, practices that can and do participate demonstrate
      exceptional managerial capability, and this year those practices are recognized
      for their participation. In this report, we continue to emphasize the methodology
      introduced last year in which we reported medical revenue net of the cost of the
      drugs as net medical revenue for the hematology/oncology product line. The effect
      of this is to capture only the gross margin attributable to drugs as revenue. New
      this year, we introduce six measures of clinical data density and expand the
      radiation oncology benchmarks. 

PMID- 25398961
TI  - Erratum.

PMID- 25398960
TI  - Oncology practice trends from the National Practice Benchmark.

PMID- 25398962
TI  - Palliative care and hematologic malignancies: old dog, new tricks?

PMID- 25398966
TI  - Acute targeting of general transcription factor IIB restricts cardiac hypertrophy
      via selective inhibition of gene transcription.
AB  - BACKGROUND: We previously reported that specialized and housekeeping genes are
      differentially regulated via de novo recruitment and pause-release of RNA
      polymerase II, respectively, during cardiac hypertrophy. However, the
      significance of this finding remains to be examined. Therefore, the purpose of
      this study was to determine the mechanisms that differentially regulate these
      gene groups and exploit them for therapeutic targeting. METHODS AND RESULTS:
      Here, we show that general transcription factor IIB (TFIIB) and cyclin-dependent
      kinase 9 are upregulated during hypertrophy, both targeted by microRNA-1, and
      play preferential roles in regulating those 2 groups of genes. Chromatin
      immunoprecipitation-sequencing reveals that TFIIB is constitutively bound to all
      paused, housekeeping, promoters, whereas de novo recruitment of TFIIB and
      polymerase II is required for specialized genes that are induced during
      hypertrophy. We exploited this dichotomy to acutely inhibit induction of the
      latter set, which encompasses cardiomyopathy, immune reaction, and extracellular
      matrix genes, using locked nucleic acid-modified antisense TFIIB oligonucleotide
      treatment. This resulted in suppression of all specialized genes, while sparing
      the housekeeping ones, and, thus, attenuated pathological hypertrophy.
      CONCLUSIONS: The data for the first time reveal distinct general TFIIB dynamics
      that regulate specialized versus housekeeping genes during cardiac hypertrophy.
      Thus, by acutely targeting TFIIB, we were able to inhibit selectively the former
      set of genes and ameliorate pressure overload hypertrophy. We also demonstrate
      the feasibility of acutely and reversibly targeting cardiac mRNA for therapeutic
      purposes using locked nucleic acid-modified antisense oligonucleotides.

PMID- 25398969
TI  - The sun is not hurried by early risers.

PMID- 25398968
TI  - Differential effects of tumor necrosis factor-alpha on matrix metalloproteinase-2
      expression in human myometrial and uterine leiomyoma smooth muscle cells.
AB  - STUDY QUESTION: Does tumor necrosis factor-alpha (TNF-alpha) differentially
      regulate matrix metalloproteinase-2 (MMP-2) expression in leiomyomas compared
      with normal myometrium? SUMMARY ANSWER: TNF-alpha up-regulates MMP-2 expression
      and stimulates cell migration through the activation of extracellular signal
      regulated kinase (ERK) signaling pathway in leiomyoma smooth muscle cells (SMCs),
      but not in normal myometrial SMCs. WHAT IS KNOWN ALREADY: Uterine leiomyoma, the
      benign smooth muscle cell tumor, is the single most common indication for
      hysterectomy. High expression of MMPs or TNF-alpha has been reported in uterine
      leiomyomas; however, the molecular mechanism underlying these observations
      remains unknown. STUDY DESIGN, SIZE, DURATION: Samples were obtained between 2009
      and 2013 from 12 women of reproductive age at the proliferative phase of the
      menstrual cycle by hysterectomy. Leiomyomas and matched normal myometrium from
      each woman were analyzed in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Western blot, RT-qPCR and a wound-healing assay were used to investigate the
      effects of TNF-alpha on MMP-2 expression and intracellular signal transduction in
      cultured SMCs from leiomyomas and matched myometrium. MAIN RESULTS AND THE ROLE
      OF CHANCE: Western blot and RT-qPCR analyses using tissues from clinical patients
      showed that the levels of MMP-2 protein (P = 0.008) and mRNA (P = 0.009) were
      significantly higher in uterine leiomyomas compared with their matched
      myometrium. Treatment with TNF-alpha significantly up-regulated the protein (P =
      0.039) and mRNA (P = 0.037) levels of MMP-2 in cultured leiomyoma SMCs but not in
      matched myometrial SMCs. The extracellular signal-regulated kinase (ERK) and
      nuclear factor-kappa B (NF-kappaB) pathways were activated by TNF-alpha in
      leiomyoma SMCs. Specific inhibitors of the ERK or NF-kappaB pathway (PD98059 or
      Bay11-7082) suppressed TNF-alpha-induced MMP-2 expression in leiomyoma SMCs. The
      wound-healing assay revealed that TNF-alpha promoted the migration of cultured
      leiomyoma SMCs (P = 0.036); however, PD98059 compromised the cell migration
      triggered by TNF-alpha. LIMITATIONS, REASONS FOR CAUTION: This study is
      descriptive and although we observed clear differential regulation of MMP-2 by
      TNF-alpha at mRNA and protein levels in leiomyoma, future studies are needed to
      identify why the difference in TNF-alpha response exists between human leiomyoma
      tissue and normal myometrium. Including some of the experiments such as
      transfection studies for TNF-alpha and MMP-2 promoter mapping could have added
      more insight as to why this difference exists. In addition, further studies in
      vivo are needed to verify the results obtained from primary cultured SMCs. WIDER
      IMPLICATIONS OF THE FINDINGS: Considering the positive effect of TNF-alpha on
      leiomyoma SMC migration, strategies targeting TNF-alpha, in parallel with the
      production of more specific inhibitors of MMPs, may provide alternative
      therapeutic approaches for the treatment of leiomyoma. STUDY FUNDING/COMPETING
      INTERESTS: This work was partially supported by grants from the Program for New
      Century Excellent Talents in University (NCET-12-0282), National Natural Science
      Foundation of China (81371620) and Tianjin Natural Science Foundation
      (12JCZDJC24900). The authors have no conflicts of interest to declare.

PMID- 25398967
TI  - Risk of heart failure among postmenopausal women: a secondary analysis of the
      randomized trial of vitamin D plus calcium of the women's health initiative.
AB  - BACKGROUND: Vitamin D supplementation may be an inexpensive intervention to
      reduce heart failure (HF) incidence. However, there are insufficient data to
      support this hypothesis. This study evaluates whether vitamin D plus calcium
      (CaD) supplementation is associated with lower rates of HF in postmenopausal
      women and whether the effects differ between those at high versus low risk for
      HF. METHODS AND RESULTS: Analyses were restricted to 35 983 (of original 36 282)
      women aged 50 to 79 years old in the Women's Health Initiative randomized trial
      of CaD supplementation who were randomized 1:1 in a double-blinded fashion to
      receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744
      adjudicated incident HF cases (intervention, 363; control, 381) occurred during a
      median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation,
      compared with placebo, was not associated with reduced HF risk in the overall
      population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had
      differential effects (P interaction=0.005) in subgroups stratified by baseline
      risk status of HF defined by the presence (high risk=17 449) or absence (low
      risk=18 534) of pre-existing HF precursors including coronary heart diseases,
      diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence
      interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06;
      P=0.51, in the high-risk subgroups. CONCLUSIONS: CaD supplementation did not
      significantly reduce HF incidence in the overall cohort, however, it was
      beneficial among postmenopausal women without major HF precursors while of little
      value in high-risk subgroups. Additional studies are warranted to confirm these
      findings and investigate the underlying mechanism. CLINICAL TRIAL REGISTRATION
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

PMID- 25398970
TI  - Mental distress and personality in women undergoing GnRH agonist versus GnRH
      antagonist protocols for assisted reproductive technology.
AB  - STUDY QUESTION: Do mental distress and mood fluctuations in women undergoing GnRH
      agonist and GnRH antagonist protocols for assisted reproductive technology (ART)
      differ depending on protocol and the personality trait, neuroticism? SUMMARY
      ANSWER: ART treatment did not induce elevated levels of mental distress in either
      GnRH antagonist or agonist protocols but neuroticism was positively associated
      with increased mental distress, independent of protocols. WHAT IS KNOWN ALREADY:
      ART treatment may increase mental distress by mechanisms linked to sex hormone
      fluctuations. General psychological characteristics, such as personality traits
      indexing negative emotionality, e.g. neuroticism, are likely to affect mental
      distress during ART treatment. STUDY DESIGN, SIZE, DURATION: A total of 83 women
      undergoing their first ART cycle were consecutively randomized 1:1 to GnRH
      antagonist (n = 42) or GnRH agonist (n = 41) protocol. The study population was a
      subgroup of a larger ongoing Danish clinical randomized trial and was established
      as an add-on in the period 2010-2012. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Women in the GnRH antagonist protocol received daily injections with recombinant
      follicle-stimulating hormone, Puregon((r)) and subcutaneous injections with GnRH
      antagonist, Orgalutran((r)). Women in the GnRH agonist protocol received nasal
      administration of the GnRH agonist, Synarela((r)) and subcutaneous injections
      with FSH, Puregon((r)). The study design did not allow for a blinding procedure.
      All women self-reported the Profile of Mood States, the Perceived Stress Scale,
      the Symptom Checklist-92-Revised, and the Major Depression Inventory
      questionnaires, at baseline, at ART cycle day 35, on the day of oocyte pick-up,
      and on the day of hCG testing. Also, a series of Profile of Mood States were
      reported daily during pharmacological treatment to monitor mood fluctuations. The
      personality trait Neuroticism was assessed at baseline by the self-reported NEO
      PI-R questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: ART did not induce
      within- or between-protocol changes in any of the applied measures of mental
      distress. However, the GnRH antagonist protocol was associated with more
      pronounced median mood fluctuations during the stimulation phase (antagonist,
      11.0 SD, [IQR = 21.1-6.1]; agonist, 8.9 SD, [IQR = 11.3-5.7], P = 0.025). This
      association became non-significant after applying a Bonferroni-Holm correction.
      Neuroticism was highly positively associated with increased levels of mental
      distress throughout treatment independent of protocols (all P-values <0.006), and
      cross-sectional analysis revealed that women with high or low Neuroticism scores
      at baseline showed a significant trend towards lower chances of a positive
      pregnancy test (P-value =0.028). LIMITATIONS, REASONS FOR CAUTION: Information on
      prognostic factors such as preceding length of infertility, number of retrieved
      oocytes and number of prior insemination treatments was not accounted for in the
      analyses. The stratification of protocols by age in the subgroups of women
      included in this study was suboptimal. Women with prior or current use of
      antidepressant medication were excluded from our study. WIDER IMPLICATIONS: Our
      results imply that mental distress emerging during ART treatment is not causally
      linked to hypogonadism per se or to the choice of protocol. Rather, our data
      highlight the potential importance of (i) rapid increases in ovarian steroids and
      (ii) addressing personality traits indexing negative emotionality, i.e.
      Neuroticism, in women undergoing ART treatment, to optimize both emotional
      adjustment and, possibly, the chances of obtaining pregnancy. STUDY
      FUNDING/COMPETING INTERESTS: The Danish Research Council for Independent Research
      and MSD, Denmark kindly supported the study. The authors declare no competing
      financial interests. TRIAL REGISTRATION NUMBER: EudraCT - 2008-005452-24.

PMID- 25398971
TI  - Highly purified hMG versus recombinant FSH plus recombinant LH in intrauterine
      insemination cycles in women >=35 years: a RCT.
AB  - STUDY QUESTION: Is the treatment with recombinant FSH (rFSH) plus recombinant LH
      (rLH) more effective than highly purified (HP)-hMG in terms of ongoing pregnancy
      rate (PR) in women >=35 years of age undergoing intrauterine insemination (IUI)
      cycles? SUMMARY ANSWER: The ongoing PR was not significantly different in women
      treated with rFSH plus rLH or with HP-hMG. WHAT IS KNOWN ALREADY: Although
      previous studies have shown beneficial effects of the addition of LH activity to
      FSH, in terms of PR in patients aged over 34 years having ovulation induction, no
      studies have compared two different gonadotrophin preparations containing LH
      activity in women >=35 years of age in IUI cycles. STUDY DESIGN, SIZE, DURATION:
      A single-centre RCT was performed between May 2012 and September 2013 with 579
      women >=35 years of age undergoing IUI cycles. The patients were randomly
      assigned to one of the two groups, rFSH in combination with rLH group or HP-hMG
      (Meropur) group, by giving them a code number from a computer generated
      randomization list, in order of enrolment. The randomization visit took place on
      the first day of ovarian stimulation. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Five hundred and seventy-nine patients with unexplained infertility or mild male
      factor undergoing IUI cycles were recruited in a university hospital setting. All
      women were enrolled in this study only for one cycle of treatment. Five hundred
      and seventy-nine cycles were included in the final analysis. Two hundred and
      ninety patients were treated with rFSH in combination with rLH and 289 patients
      were treated with HP-hMG. The ovarian stimulation cycle started on the third day
      of the menstrual cycle and the starting gonadotrophin doses used were 150 IU/day
      of rFSH plus 150 IU/day of rLH or 150 IU/day of HP-hMG. The drug dose was
      adjusted according to the individual follicular response. A single IUI per cycle
      was performed 34-36 h after hCG injection. MAIN RESULTS AND THE ROLE OF CHANCE:
      The main outcome measures were ongoing PR and number of interrupted cycles for
      high risk of ovarian hyperstimulation syndrome (OHSS). Ongoing pregnancy rates
      were 48/290 (17.3%) in the recombinant group versus 35/289 (12.2%) in the HP-hMG
      group [(odds ratio (OR) 1.50, 95% CI 0.94-2.41, P = 0.09]. The number of
      interrupted cycles for high risk of OHSS was 13/290 (4.5%) in the rFSH plus rLH
      group and 2/289 (0.7%) in the HP-hMG group (OR 6.73, 95% CI 1.51-30.12, P =
      0.013). LIMITATIONS, REASONS FOR CAUTION: One of the limitations of this study
      was the early closure and the ongoing PR could be overestimated. Both patient and
      gynaecologist were informed of the assigned treatment. WIDER IMPLICATIONS OF THE
      FINDINGS: Our results demonstrated the lack of differences in terms of ongoing PR
      between recombinant product and HP-hMG, in women >=35 years undergoing controlled
      ovarian stimulation for IUI cycles. HP-hMG was safer than recombinant
      gonadotrophin concerning the risk of OHSS. STUDY FUNDING/COMPETING INTERESTS:
      None. TRIAL REGISTRATION NUMBER: NCT01604044.

PMID- 25398972
TI  - Memory-guided tracking through physical space and feature space.
AB  - People can estimate the current position of an occluded moving target. This is
      called motion extrapolation, and it has been suggested that the performance in
      such tasks is mediated by the smooth-pursuit system. Experiment 1 contrasted a
      standard position extrapolation task with a novel number extrapolation task. In
      the position extrapolation task, participants saw a horizontally moving target
      become occluded, and then responded when they thought the target had reached the
      end of the occluder. Here the stimuli can be tracked with pursuit eye movements.
      In the number extrapolation task, participants saw a rapid countdown on the
      screen that disappeared before reaching zero. Participants responded when they
      thought the hidden counter would have reached zero. Although this stimulus cannot
      be tracked with the eyes, performance was comparable on both the tasks. The
      response times were also found to be correlated. Experiments 2 and 3 extended
      these findings, using extrapolation through color space as well as number space,
      while Experiment 4 found modest evidence for similarities between color and
      number extrapolation. Although more research is certainly needed, we propose that
      a common rate controller guides extrapolation through physical space and feature
      space. This functions like the velocity store module of the smooth-pursuit
      system, but with a broader function than previously envisaged. 

PMID- 25398973
TI  - Paper features: a neglected source of information for letter recognition.
AB  - Adult observers have surprisingly low calculation efficiencies for letter
      recognition (see, e.g., Pelli, Burns, Farell, & Moore-Page, 2006). Here, we
      examine the possibility that this is partly due to observers' neglecting paper
      features (e.g., the absence of ascenders and descenders in 'o'). Each of 16
      observers completed 5,000 trials of a single-letter two-alternative forced-choice
      detection task. Using a combination of classification image analyses and Bayesian
      statistical analyses, we argue that between 60% and 75% of our participants
      indeed neglected paper features. 

PMID- 25398974
TI  - Vernier perceptual learning transfers to completely untrained retinal locations
      after double training: a "piggybacking" effect.
AB  - Perceptual learning, a process in which training improves visual discrimination,
      is often specific to the trained retinal location, and this location specificity
      is frequently regarded as an indication of neural plasticity in the retinotopic
      visual cortex. However, our previous studies have shown that "double training"
      enables location-specific perceptual learning, such as Vernier learning, to
      completely transfer to a new location where an irrelevant task is practiced. Here
      we show that Vernier learning can be actuated by less location-specific
      orientation or motion-direction learning to transfer to completely untrained
      retinal locations. This "piggybacking" effect occurs even if both tasks are
      trained at the same retinal location. However, piggybacking does not occur when
      the Vernier task is paired with a more location-specific contrast-discrimination
      task. This previously unknown complexity challenges the current understanding of
      perceptual learning and its specificity/transfer. Orientation and motion
      direction learning, but not contrast and Vernier learning, appears to activate a
      global process that allows learning transfer to untrained locations. Moreover,
      when paired with orientation or motion-direction learning, Vernier learning may
      be "piggybacked" by the activated global process to transfer to other untrained
      retinal locations. How this task-specific global activation process is achieved
      is as yet unknown. 

PMID- 25398975
TI  - How much to trust the senses: likelihood learning.
AB  - Our brain often needs to estimate unknown variables from imperfect information.
      Our knowledge about the statistical distributions of quantities in our
      environment (called priors) and currently available information from sensory
      inputs (called likelihood) are the basis of all Bayesian models of perception and
      action. While we know that priors are learned, most studies of prior-likelihood
      integration simply assume that subjects know about the likelihood. However, as
      the quality of sensory inputs change over time, we also need to learn about new
      likelihoods. Here, we show that human subjects readily learn the distribution of
      visual cues (likelihood function) in a way that can be predicted by models of
      statistically optimal learning. Using a likelihood that depended on color
      context, we found that a learned likelihood generalized to new priors. Thus, we
      conclude that subjects learn about likelihood. 

PMID- 25398976
TI  - Myocardial revascularization with both internal thoracic arteries 25 years after
      delayed repair for aortic coarctation.
AB  - Aortic coarctation has been reported to cause alterations in the internal
      thoracic arteries that make these vessels unsuitable to be used as grafts for
      myocardial revascularization, especially if coarctation repair was performed in
      adulthood. This is the first reported bilateral internal thoracic grafting for
      myocardial revascularization in a patient who had undergone aortic coarctation
      repair 25 years earlier. 

PMID- 25398977
TI  - Is it safe and worthwhile to perform pulmonary resection after contralateral
      pneumonectomy?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether pulmonary resection is safe and worthwhile in
      patients who have undergone previous pneumonectomy. A total of 141 studies were
      identified using the reported search, of which 8 represented the best evidence to
      answer the clinical question. Studies on multiple lung cancers with patients
      undergoing subsequent pulmonary resection after previous pneumonectomy, without
      outcome data specifically for this group of patients and case reports, were not
      included in this analysis. The authors, date, journal, country, study type,
      population, outcomes and key results are tabulated. All studies were
      retrospective. In total, 102 patients underwent pulmonary resection after
      contralateral pneumonectomy, of which 96 had sublobar resections and 6 had
      lobectomies. Postoperative complications, reported in four of the eight studies,
      ranged from 21 to 44% (mean from four studies 36.8%). Four of the eight studies
      reported no mortality after pulmonary resection following pneumonectomy, whereas
      the other four reported mortality rates from 6.7 to 43%. For patients undergoing
      sublobar resections, the postoperative mortality was 6.2% (6/96), while for those
      submitted to lobectomy, mortality was 33.3% (2/6). Five-year survival rates
      ranged from 14% for metastatic disease to 50% for metachronous lung cancer. Due
      to the infrequent situation of a patient being considered for a pulmonary
      resection after contralateral pneumonectomy, this analysis was based on a limited
      number of patients from eight reports. Nevertheless, analysis of the data
      suggests that pulmonary resection for metastatic or metachronous disease can be
      performed with acceptable morbidity and low mortality in appropriately selected
      patients who have previously undergone a pneumonectomy. Sublobar resection is the
      treatment of choice whenever possible, for which long-term results are rewarding
      especially for patients with metachronous lung cancer. 

PMID- 25398978
TI  - Combination versus sequential monotherapy in chronic HBV infection: a
      mathematical approach.
AB  - Sequential monotherapy is the most widely used therapeutic approach in the
      treatment of hepatitis B virus (HBV) chronic infection. Unfortunately, under
      therapy, in some patients the hepatitis virus mutates and gives rise to variants
      which are drug resistant. We wonder whether those patients would have benefited
      from the choice of combination therapy instead of sequential monotherapy. To
      study the action of these two therapeutic approaches and to explain the emergence
      of drug resistance, we propose a stochastic model for the infection within a
      patient who is treated with two drugs, either sequentially or contemporaneously,
      and who, under the first kind of therapy develops a strain of the virus which is
      resistant to both drugs. Our stochastic model has a deterministic approximation
      which is a slight modification of a classic three-strain model. We discuss why
      stochastic simulations are more suitable than the study of the deterministic
      approximation, when modelling the rise of mutations (this is mainly due to the
      amplitude of the stochastic fluctuations). We run stochastic simulations with
      suitable parameters and compare the time when, under the two therapeutic
      approaches, the resistant strain first reaches detectability in the serum viral
      load. Our results show that the best choice is to start an early combination
      therapy, which allows one to stay drug resistance free for a longer time and in
      many cases leads to viral eradication. 

PMID- 25398979
TI  - A dynamic model of oxygen transport from capillaries to tissue with moving red
      blood cells.
AB  - Most oxygen required to support the energy needs of vertebrate tissues is
      delivered by diffusion from microvessels. The presence of red blood cells (RBCs)
      makes blood flow in the microcirculation highly heterogeneous. Additionally, flow
      regulation mechanisms dynamically respond to changes in tissue energy demand.
      These spatiotemporal variations directly affect the supply of oxygen to
      parenchymal cells. Due to various limiting assumptions, current models of oxygen
      transport cannot fully capture the consequences of complex hemodynamic effects on
      tissue oxygenation and are often not suitable for studying unsteady phenomena.
      With our new approach based on moving RBCs, the impact of blood flow
      heterogeneity on oxygen partial pressure (Po2) in the tissue can be quantified.
      Oxygen transport was simulated using parachute-shaped solid RBCs flowing through
      a capillary. With the use of a conical tissue domain with radii 19 and 13 MUm,
      respectively, our computations indicate that Po2 at the RBC membrane exceeds Po2
      between RBCs by 30 mmHg on average and that the mean plasma Po2 decreases by 9
      mmHg over 50 MUm. These results reproduce well recent intravascular Po2
      measurements in the rodent brain. We also demonstrate that instantaneous
      variations of capillary hematocrit cause associated fluctuations of tissue Po2.
      Furthermore, our results suggest that homogeneous tissue oxygenation requires
      capillary networks to be denser on venular side than on arteriolar side. Our new
      model for oxygen transport will make it possible to quantify in detail the
      effects of blood flow heterogeneity on tissue oxygenation in realistic capillary
      networks. 

PMID- 25398980
TI  - A new hemodynamic model for the study of cerebral venous outflow.
AB  - We developed a mathematical model of the cerebral venous outflow for the
      simulation of the average blood flows and pressures in the main drainage vessels
      of the brain. The main features of the model are that it includes a validated
      model for the simulation of the intracranial circulation and it accounts for the
      dependence of the hydraulic properties of the jugular veins with respect to the
      gravity field, which makes it an useful tool for the study of the correlations
      between extracranial blood redistributions and changes in the intracranial
      environment. The model is able to simulate the average pressures and flows in
      different points of the jugular ducts, taking into account the amount of blood
      coming from the anastomotic connections; simulate how the blood redistribution
      due to change of posture affects flows and pressures in specific points of the
      system; and simulate redistributions due to stenotic patterns. Sensitivity
      analysis to check the robustness of the model was performed. The model reproduces
      average physiologic behavior of the jugular, vertebral, and cerebral ducts in
      terms of pressures and flows. In fact, jugular flow drops from ~11.7 to ~1.4 ml/s
      in the passage from supine to standing. At the same time, vertebral flow
      increases from 0.8 to 3.4 ml/s, while cerebral blood flow, venous sinuses
      pressure, and intracranial pressure are constant around the average value of 12.5
      ml/s, 6 mmHg, and 10 mmHg, respectively. All these values are in agreement with
      literature data. 

PMID- 25398981
TI  - Measurement bias in activation-recovery intervals from unipolar electrograms.
AB  - The activation-recovery interval (ARI) calculated from unipolar electrograms is
      regularly used as a convenient surrogate measure of local cardiac action
      potential durations (APD). This method enables important research bridging
      between computational studies and in vitro and in vivo human studies. The Wyatt
      method is well established as a theoretically sound method for calculating ARIs;
      however, some studies have observed that it is prone to a bias error in
      measurement when applied to positive T waves. This article demonstrates that
      recent theoretical and computational studies supporting the use of the Wyatt
      method are likely to have underestimated the extent of this bias in many
      practical experimental recording scenarios. This work addresses these situations
      and explains the measurement bias by adapting existing theoretical expressions of
      the electrogram to represent practical experimental recording configurations. A
      new analytic expression for the electrogram's local component is derived, which
      identifies the source of measurement bias for positive T waves. A computer
      implementation of the new analytic model confirms our hypothesis that the bias is
      systematically dependent on the electrode configuration. These results provide an
      aid to electrogram interpretation in general, and this work's outcomes are used
      to make recommendations on how to minimize measurement error. 

PMID- 25398982
TI  - Hypertension overrides the protective effect of female hormones on the
      development of aortic aneurysm secondary to Alk5 deficiency via ERK activation.
AB  - The prevalence of aortic aneurysm is five times higher in men than women among
      the general population. Similar sexual dimorphism also exists in syndromic aortic
      aneurysms triggered by TGF-beta signaling disorders. To understand the
      responsible mechanisms, we developed an animal model where inducible deletion of
      the type I TGF-beta receptor, Alk5, specifically in smooth muscle cells (Alk5iko)
      causes spontaneous aortic aneurysm formation. This model recapitulated an extreme
      scenario of the dimorphism in aortic aneurysm development between genders. In a
      comparative experiment, all Alk5iko males (n=42) developed aortic aneurysms and
      26% of them died prematurely from aortic rupture. In contrast, the Alk5iko
      females (n=14) presented only a subclinical phenotype characteristic of scarcely
      scattered elastin breaks. Removal of male hormones via orchiectomy (n=7) resulted
      in only minimal influence on aortic pathology. However, reduction of female
      hormones via ovariectomy (n=15) increased the phenotypic penetrance from zero to
      53%. Finally, an elevation of systolic blood pressure by 30 points unmasked the
      subclinical phenotype of Alk5iko females (n=17) to 59%. This exaggerated
      phenotypic penetrance was coupled with an early intensification of ERK signaling,
      a molecular signature that correlated to 100% phenotypic penetrance in
      normotensive Alk5iko males. In conclusion, aortic aneurysm induced by Alk5iko
      exhibits dimorphic incidence between genders with females less susceptible to
      aortic disease. This sexual dimorphism is partially the result from the
      protective effects of female hormones. Hypertension, a known risk factor for
      aortic aneurysm, is able to break the female sex protective effects through
      mechanisms associated with enhanced ERK activity.

PMID- 25398983
TI  - Diet and sex modify exercise and cardiac adaptation in the mouse.
AB  - The heart adapts to exercise stimuli in a sex-dimorphic manner when mice are fed
      the traditional soy-based chow. Females undergo more voluntary exercise (4 wk)
      than males and exhibit more cardiac hypertrophy per kilometer run (18, 32). We
      have found that diet plays a critical role in cage wheel exercise and cardiac
      adaptation to the exercise stimulus in this sex dimorphism. Specifically, feeding
      male mice a casein-based, soy-free diet increases daily running distance over soy
      fed counterparts to equal that of females. Moreover, casein-fed males have a
      greater capacity to increase their cardiac mass in response to exercise compared
      with soy-fed males. To further explore the biochemical mechanisms for these
      differences, we performed a candidate-based RT-PCR screen on genes previously
      implicated in diet- or exercise-based cardiac hypertrophy. Of the genes screened,
      many exhibit significant exercise, diet, or sex effects but only transforming
      growth factor-beta1 shows a significant three-way interaction with no genes
      showing a two-way interaction. Finally, we show that the expression and activity
      of adenosine monophosphate-activated kinase-alpha2 and acetyl-CoA carboxylase is
      dependent on exercise, diet, and sex. 

PMID- 25398985
TI  - A preterm pig model of lung immaturity and spontaneous infant respiratory
      distress syndrome.
AB  - Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia remain the
      leading causes of preterm infant morbidity, mortality, and lifelong disability.
      Research to improve outcomes requires translational large animal models for RDS.
      Preterm pigs delivered by caesarian section at gestation days (GD) 98, 100, 102,
      and 104 were provided 24 h of neonatal intensive care, monitoring (pulse
      oximetry, blood gases, serum biomarkers, radiography), and nutritional support,
      with or without intubation and mechanical ventilation (MV; pressure control
      ventilation with volume guarantee). Spontaneous development of RDS and mortality
      without MV are inversely related with GD at delivery and correspond with
      inadequacy of tidal volume and gas exchange. GD 98 and 100 pigs have consolidated
      lungs, immature alveolar architecture, and minimal surfactant protein-B
      expression, and MV is essential at GD 98. Although GD 102 pigs had some alveoli
      lined by pneumocytes and surfactant was released in response to MV, blood gases
      and radiography revealed limited recruitment 1-2 h after delivery, and mortality
      at 24 h was 66% (35/53) with supplemental oxygen provided by a mask and 69%
      (9/13) with bubble continuous positive airway pressure (8-9 cmH2O). The lungs at
      GD 104 had higher densities of thin-walled alveoli that secreted surfactant, and
      MV was not essential. Between GD 98 and 102, preterm pigs have ventilation
      inadequacies and risks of RDS that mimic those of preterm infants born during the
      saccular phase of lung development, are compatible with standards of neonatal
      intensive care, and are alternative to fetal nonhuman primates and lambs. 

PMID- 25398984
TI  - Recent progress in research on molecular mechanisms of autophagy in the heart.
AB  - Dysregulation of autophagy, an evolutionarily conserved process for degradation
      of long-lived proteins and organelles, has been implicated in the pathogenesis of
      human disease. Recent research has uncovered pathways that control autophagy in
      the heart and molecular mechanisms by which alterations in this process affect
      cardiac structure and function. Although initially thought to be a nonselective
      degradation process, autophagy, as it has become increasingly clear, can exhibit
      specificity in the degradation of molecules and organelles, such as mitochondria.
      Furthermore, it has been shown that autophagy is involved in a wide variety of
      previously unrecognized cellular functions, such as cell death and metabolism. A
      growing body of evidence suggests that deviation from appropriate levels of
      autophagy causes cellular dysfunction and death, which in turn leads to heart
      disease. Here, we review recent advances in understanding the role of autophagy
      in heart disease, highlight unsolved issues, and discuss the therapeutic
      potential of modulating autophagy in heart disease. 

PMID- 25398986
TI  - Transcriptional mechanisms and protein kinase signaling mediate organic dust
      induction of IL-8 expression in lung epithelial and THP-1 cells.
AB  - Exposure to the agricultural work environment is a risk factor for the
      development of respiratory symptoms and chronic lung diseases. Inflammation is an
      important contributor to the pathogenesis of tissue injury and disease. Cellular
      and molecular mechanisms mediating lung inflammatory responses to agricultural
      dust are not yet fully understood. We studied the effects of poultry dust extract
      on molecular regulation of interleukin-8 (IL-8), a proinflammatory cytokine, in
      A549 and Beas2B lung epithelial and THP-1 monocytic cells. Our findings indicate
      that poultry dust extract potently induces IL-8 levels by increasing IL-8 gene
      transcription without altering IL-8 mRNA stability. Increase in IL-8 promoter
      activity was due to enhanced binding of activator protein 1 and NF-kappaB. IL-8
      induction was associated with protein kinase C (PKC) and mitogen-activated
      protein kinase (MAPK) activation and inhibited by PKC and MAPK inhibitors. IL-8
      increase was not inhibited by polymyxin B or l-nitroarginine methyl ester,
      indicating lack of involvement of lipopolysaccharide and nitric oxide in the
      induction. Lung epithelial and THP-1 cells share common mechanisms for induction
      of IL-8 levels. Our findings identify key roles for transcriptional mechanisms
      and protein kinase signaling pathways for IL-8 induction and provide insights
      into the mechanisms regulating lung inflammatory responses to organic dust
      exposure. 

PMID- 25398987
TI  - Abnormal epithelial structure and chronic lung inflammation after repair of
      chlorine-induced airway injury.
AB  - Chlorine is a toxic gas used in a variety of industrial processes and is
      considered a chemical threat agent. High-level chlorine exposure causes acute
      lung injury, but the long-term effects of acute chlorine exposure are unclear.
      Here we characterized chronic pulmonary changes following acute chlorine exposure
      in mice. A/J mice were exposed to 240 parts per million-hour chlorine or sham
      exposed to air. Chlorine inhalation caused sloughing of bronchial epithelium 1
      day after chlorine exposure, which was repaired with restoration of a
      pseudostratified epithelium by day 7. The repaired epithelium contained an
      abnormal distribution of epithelial cells containing clusters of club or ciliated
      cells rather than the uniformly interspersed pattern of these cells in unexposed
      mice. Although the damaged epithelium in A/J mice was repaired rapidly, and
      minimal airway fibrosis was observed, chlorine-exposed mice developed pneumonitis
      characterized by infiltration of alveoli with neutrophils and prominent, large,
      foamy macrophages. Levels of CXCL1/KC, CXCL5/LPS-induced CXC chemokine,
      granulocyte colony-stimulating factor, and VEGF in bronchoalveolar (BAL) fluid
      from chlorine-exposed mice showed steadily increasing trends over time. BAL
      protein levels were increased on day 4 and remained elevated out to day 28. The
      number of bacteria cultured from lungs of chlorine-exposed mice 4 wk after
      exposure was not increased compared with sham-exposed mice, indicating that the
      observed pneumonitis was not driven by bacterial infection of the lung. The
      results indicate that acute chlorine exposure may cause chronic abnormalities in
      the lungs despite rapid repair of injured epithelium. 

PMID- 25398988
TI  - A mathematical model to predict protein wash out kinetics during whole-lung
      lavage in autoimmune pulmonary alveolar proteinosis.
AB  - Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar
      proteinosis (PAP), a process in which accumulated surfactants are washed out of
      the lung with 0.5-2.0 l of saline aliquots for 10-30 wash cycles. The method has
      been established empirically. In contrast, the kinetics of protein transfer into
      the lavage fluid has not been fully evaluated either theoretically or
      practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We
      made accurate timetables for each stage of WLL, namely, instilling, retaining,
      draining, and preparing. Subsequently, we measured the volumes of both instilled
      saline and drained lavage fluid, as well as the concentrations of proteins in the
      drained lavage fluid. We also proposed a mathematical model of protein transfer
      into the lavage fluid in which time is a single variable as the protein moves in
      response to the simple diffusion. The measured concentrations of IgG,
      transferrin, albumin, and beta2-microglobulin closely matched the corresponding
      theoretical values calculated through differential equations. Coefficients for
      transfer of beta2-microglobulin from the blood to the lavage fluid were two
      orders of magnitude higher than those of IgG, transferrin, and albumin.
      Simulations using the mathematical model showed that the cumulative amount of
      eliminated protein was not affected by the duration of each cycle but dependent
      mostly on the total time of lavage and partially on the volume instilled.
      Although physicians have paid little attention to the transfer of substances from
      the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion
      based mathematical model. 

PMID- 25398990
TI  - In vino veritas? Alcohol, response inhibition and lying.
AB  - AIMS: Despite the widespread belief that alcohol makes the truth come out more
      easily, we know very little on how alcohol impacts deception. Given that alcohol
      impairs response inhibition, and that response inhibition may be critically
      involved in deception, we expected that alcohol intake would hamper lying.
      METHODS: In total, 104 volunteers were tested at a science festival, where they
      had the opportunity to drink alcohol. Stop-Signal Reaction Times (SSRTs) served
      as operationalization of response inhibition. Differences in error rates and
      reaction times (RTs) between lying and truth telling served as indicators of the
      cognitive cost of lying. RESULTS: Higher blood alcohol concentration was related
      to longer SSRTs, but unrelated to the cognitive costs of lying. CONCLUSION: This
      study validates previous laboratory research on alcohol and response inhibition
      in a realistic drinking environment, yet failed to find an effect of alcohol on
      lying. Implications of these findings and for the role of response inhibition in
      lying are discussed.

PMID- 25398991
TI  - The cytoplasmic peptide:N-glycanase (Ngly1)-basic science encounters a human
      genetic disorder.
AB  - Peptide:N-glycanase (PNGase) is a de-N-glycosylating enzyme that cleaves intact N
      glycans from glycoproteins/glycopeptides. The activity of the cytoplasmic PNGase
      in several mammalian-derived cultured cells was first reported in 1993, and 7
      years later, the gene encoding the enzyme was identified in budding yeast.
      Although the gene-PNG1 in budding yeast and NGLY1/Ngly1 in mammalian cells
      appears to be well conserved throughout eukaryotes, the biological significance
      of this enzyme has remained elusive until recently. However, discovery of a human
      genetic disorder involving the NGLY1 gene clearly indicates that this enzyme
      plays a critical role in human biology. This review summarizes the research
      history of cytoplasmic PNGase. The importance of curiosity-driven, pure 'basic
      science' will also be discussed. 

PMID- 25398989
TI  - Vasculopathy and pulmonary hypertension in sickle cell disease.
AB  - Sickle cell disease (SCD) is an autosomal recessive disorder in the gene encoding
      the beta-chain of hemoglobin. Deoxygenation causes the mutant hemoglobin S to
      polymerize, resulting in rigid, adherent red blood cells that are entrapped in
      the microcirculation and hemolyze. Cardinal features include severe painful
      crises and episodic acute lung injury, called acute chest syndrome. This
      population, with age, develops chronic organ injury, such as chronic kidney
      disease and pulmonary hypertension. A major risk factor for developing chronic
      organ injury is hemolytic anemia, which releases red blood cell contents into the
      circulation. Cell free plasma hemoglobin, heme, and arginase 1 disrupt
      endothelial function, drive oxidative and inflammatory stress, and have recently
      been referred to as erythrocyte damage-associated molecular pattern molecules
      (eDAMPs). Studies suggest that in addition to effects of cell free plasma
      hemoglobin on scavenging nitric oxide (NO) and generating reactive oxygen species
      (ROS), heme released from plasma hemoglobin can bind to the toll-like receptor 4
      to activate the innate immune system. Persistent intravascular hemolysis over
      decades leads to chronic vasculopathy, with ~10% of patients developing pulmonary
      hypertension. Progressive obstruction of small pulmonary arterioles, increase in
      pulmonary vascular resistance, decreased cardiac output, and eventual right heart
      failure causes death in many patients with this complication. This review
      provides an overview of the pathobiology of hemolysis-mediated endothelial
      dysfunction and eDAMPs and a summary of our present understanding of diagnosis
      and management of pulmonary hypertension in sickle cell disease, including a
      review of recent American Thoracic Society (ATS) consensus guidelines for risk
      stratification and management. 

PMID- 25398992
TI  - Isolation and functional analysis of yeast ubiquitin ligase Rsp5 variants that
      alleviate the toxicity of human alpha-synuclein.
AB  - The essential ubiquitin ligase Rsp5 is a key enzyme involved in the degradation
      of abnormal or unfavourable proteins in the yeast Saccharomyces cerevisiae.
      Overexpression of human alpha-synuclein (alpha-syn), a small lipid-binding
      protein implicated in several neurodegenerative diseases, in S. cerevisiae leads
      to growth inhibition due to many intracellular defects, including accumulation of
      reactive oxygen species (ROS). Here, to understand the mechanism of Rsp5-mediated
      detoxification of alpha-syn, we isolated novel Rsp5 variants (T255A, D295G, P343S
      and N427D), which conferred alpha-syn tolerance to yeast cells. Interestingly,
      these mutants were phenotypically distinguished from our previously identified
      RSP5(T357A) mutation, which increases ubiquitination of the general amino acid
      permease Gap1. Among them, the RSP5(P343S) substitution accelerated the
      degradation of alpha-syn, suppressed the accumulation of intracellular ROS and
      enhanced the interaction with alpha-syn and its ubiquitination. In contrast, the
      RSP5(T255A) mutation did not contribute to degradation of alpha-syn, but improved
      cell growth under acetate stress conditions, possibly leading to alleviation of
      the alpha-syn toxicity. Thus, these novel mutations might be useful not only in
      elucidating the molecular basis by which disused proteins are specifically
      recognized and effectively removed but also in screening drug candidates for
      neurodegenerative diseases or in improving ethanol production under acidic
      fermentation conditions. 

PMID- 25398993
TI  - KIT genetic alterations in anorectal melanomas.
AB  - BACKGROUND: Mucosal melanomas (MM) represent a heterogeneous tumour population
      that exhibits site-specific molecular profiles. AIMS: In a multicentre
      retrospective study, we investigated KIT aberrations in primary anorectal (AR)
      melanomas compared with melanoma metastatic to the gastrointestinal (GI) tract.
      METHODS: Primary AR MM (n=31) and GI metastatic melanoma (n=27) were studied for
      KIT mutations on exons 11, 13, 17 and 18 by high-resolution melting analysis,
      direct sequencing and c-KIT expression by immunohistochemistry. Selected cases
      were also investigated for increased KIT gene copy number by fluorescent in situ
      hybridisation. RESULTS: Functional KIT mutations were demonstrated in 11/31
      (35.5%) of AR melanomas and in 1/26 (3.8%) of GI melanoma metastases (p=0.004). A
      significant difference emerged between primary and metastatic MM with regards to
      KIT-positive immunostaining (p=0.002). Immunohistochemical c-KIT protein
      overexpression did not correlate with KIT mutational status. Increased KIT copy
      number was demonstrated in 5/20 AR primary cases. CONCLUSIONS: The rate of
      functional mutations in KIT is significantly higher in AR MM than in GI
      metastatic melanoma. KIT protein overexpression does not correlate with KIT
      mutations and cannot be used for screening purposes. Recognising the molecular
      heterogeneity of MM helps to identify patients who require a different
      therapeutic approach.

PMID- 25398994
TI  - Photo quiz: All that glitters is not gold!

PMID- 25398995
TI  - Low-positive histoplasma antigen results in the MVista assay should not be
      assumed to be false positive.

PMID- 25398996
TI  - Reply to "Low-positive histoplasma antigen results in the MVista assay should not
      be assumed to be false positive".

PMID- 25398997
TI  - Evaluation of a modified small membrane filtration method.

PMID- 25398998
TI  - Tn4401 carrying blaKPC is inserted within another insertion in pKpQIL and related
      plasmids.

PMID- 25398999
TI  - Reply to "Tn4401 carrying blaKPC is inserted within another insertion in pKpQIL
      and related plasmids".

PMID- 25399000
TI  - Helicobacter pylori vacA as marker for gastric cancer and gastroduodenal
      diseases: one but not the only factor.

PMID- 25399001
TI  - Reply to "Helicobacter pylori vacA as marker for gastric cancer and
      gastroduodenal diseases: one but not the only factor".

PMID- 25399005
TI  - Dihydroxyacid dehydratase is important for gametophyte development and disruption
      causes increased susceptibility to salinity stress in Arabidopsis.
AB  - Dihydroxyacid dehydratase (DHAD) catalyses a key step in the branched-chain amino
      acid (BCAA) biosynthetic pathway that exists in numerous organisms, including
      bacteria, fungi, and plants, but not humans. In Arabidopsis thaliana, DHAD is
      encoded by a single gene (AT3G23940), but its biological function in controlling
      plant development remains uncharacterized. In this study, we showed that DHAD is
      highly expressed in most vegetative and reproductive tissues. It is an essential
      gene, and complete disruption caused partial sterility in both male and female
      gametophyte phases. In addition, reduced expression of DHAD in knockdown mutants
      resulted in a reduction in the accumulation of all three BCAAs in roots and, as a
      consequence, led to a shorter root phenotype, which could be restored by an
      exogenous supplement of free BCAAs. Interestingly, the knockdown mutants became
      hypersensitive to salt stress, not to heavy metal stress, implying that BCAAs may
      act as osmolytes in salt tolerance. This would be the second amino acid shown to
      confer such a function in addition to the well-documented proline. Our results
      provide evidence that BCAA biosynthesis plays important roles in gametophyte and
      root development, and BCAA homeostasis contributes to the adaptation of
      Arabidopsis to salinity stress. 

PMID- 25399006
TI  - How light, temperature, and measurement and growth [CO2] interactively control
      isoprene emission in hybrid aspen.
AB  - Plant isoprene emissions have been modelled assuming independent controls by
      light, temperature and atmospheric [CO2]. However, the isoprene emission rate is
      ultimately controlled by the pool size of its immediate substrate, dimethylallyl
      diphosphate (DMADP), and isoprene synthase activity, implying that the
      environmental controls might interact. In addition, acclimation to growth [CO2]
      can shift the share of the control by DMADP pool size and isoprene synthase
      activity, and thereby alter the environmental sensitivity. Environmental controls
      of isoprene emission were studied in hybrid aspen (Populus tremula * Populus
      tremuloides) saplings acclimated either to ambient [CO2] of 380 MUmol mol(-1) or
      elevated [CO2] of 780 MUmol mol(-1). The data demonstrated strong interactive
      effects of environmental drivers and growth [CO2] on isoprene emissions. Light
      enhancement of isoprene emission was the greatest at intermediate temperatures
      and was greater in elevated-[CO2]-grown plants, indicating greater enhancement of
      the DMADP supply. The optimum temperature for isoprene emission was higher at
      lower light, suggesting activation of alternative DMADP sinks at higher light. In
      addition, [CO2] inhibition of isoprene emission was lost at a higher temperature
      with particularly strong effects in elevated-[CO2]-grown plants. Nevertheless,
      DMADP pool size was still predicted to more strongly control isoprene emission at
      higher temperatures in elevated-[CO2]-grown plants. We argue that interactive
      environmental controls and acclimation to growth [CO2] should be incorporated in
      future isoprene emission models at the level of DMADP pool size. 

PMID- 25399008
TI  - Interventional treatment for structural heart disease: who is deciding, and can
      we afford it?
AB  - During the last years, the numbers of interventions in structural heart disease
      such as transcatheter aortic valve implantation (TAVI), percutaneous treatment of
      mitral regurgitation using the MitraClip, closure of atrial septal defects (ASD)
      and others have constantly increased. While the 20th century was called the
      century of surgery, it appears that the present century might be the century of
      minimally invasive percutaneous therapy. The reduced invasiveness of these
      procedures and the success in elderly patients make these treatments increasingly
      attractive for younger and healthier patients. Now that these procedures are
      moving forward, some questions arise, namely, who is deciding on treatment
      modality, and can we afford it? 

PMID- 25399009
TI  - Phosphorylation sites of HER2/c-erbB-2: role in cell growth and in disease.
AB  - The protein kinase c-erbB-2 belongs to the family of receptor tyrosine kinase and
      is involved in oncogenesis. The present study predicts different phosphorylation
      sites of HER2/c-erbB-2 which are important in preventing or developing cancer,
      especially breast cancer. Sequence homology showed highest homology (77%) with
      epidermal growth factor receptor kinase domain. According to PROSITE search
      result, active sites of c-erbB-2 are N-lobe (glycine rich phosphate binding
      loop). Catalytic loop with presumptive catalytically active of Asp108 is
      phosphorylated by tyrosine protein kinase. A-loop, activation loop, becomes
      phosphorylated and activates the substrate binding. The study strengthens our
      knowledge regarding HER2 signaling by the detection of uncharacterized signaling
      proteins, establishing phosphorylation of an activation loop and helps us to make
      assumptions about the role of such previously unidentified proteins. On the basis
      of importance of HER2 in breast cancer as well as in other diseases, this study
      provides fruitful information for designing new therapeutic strategies. 

PMID- 25399010
TI  - Association between polymorphisms in CHRNA3 and PHACTR2 gene and environment and
      NSCLC risk in Chinese population.
AB  - Aims. This study aimed to investigate CHRNA3 (rs8040868) and PHACTR2 (rs9390123)
      single-nucleotide polymorphisms (SNPs) for association with non-small-cell lung
      cancer (NSCLC) risk in a Chinese population, and whether the environment affects
      the genetic polymorphisms. Methods. This case and control study included 500
      NSCLC patients and 500 age-matched healthy controls. CHRNA3 (rs8040868) and
      PHACTR2 (rs9390123) SNPs were genotyped and associated for NSCLC risk by
      computing the odds ratio and 95% confidence interval from multivariate
      unconditional logistic regression analyses with adjustment of age. Results. The
      minor allele frequency (MAF) of CHRNA3 (rs8040868) and PHACTR2 (rs9390123) was
      0.350 (C) and 0.397 (C), respectively. The frequencies of genotype and allele in
      CHRNA3 (rs8040868) and PHACTR2 (rs9390123) were not significantly different
      between the cases and controls, or between either of the subgroups. Conclusion.
      Although rs8040868 and rs9390123 SNPs are not associated with NSCLC risk in
      Chinese population, the results strongly suggest that geographical agents
      interact with human genetic polymorphism independent of ethnic background. 

PMID- 25399011
TI  - The social network approach in gerontological research.

PMID- 25399007
TI  - Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized
      clinical trial.
AB  - IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated
      with poor outcomes and high health care costs. Some studies suggest aspirin or
      clonidine administered during the perioperative period reduces the risk of acute
      kidney injury; however, these effects are uncertain and each intervention has the
      potential for harm. OBJECTIVE: To determine whether aspirin compared with
      placebo, and clonidine compared with placebo, alters the risk of perioperative
      acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 * 2 factorial
      randomized, blinded, clinical trial of 6905 patients undergoing noncardiac
      surgery from 88 centers in 22 countries with consecutive patients enrolled
      between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to
      take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin
      (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take
      oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a
      transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo
      patch that remained until 72 hours after surgery. MAIN OUTCOMES AND MEASURES:
      Acute kidney injury was primarily defined as an increase in serum creatinine
      concentration from the preoperative concentration by either an increase of 0.3
      mg/dL or greater (>=26.5 MUmol/L) within 48 hours of surgery or an increase of
      50% or greater within 7 days of surgery. RESULTS: Aspirin (n = 3443) vs placebo
      (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%,
      respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n =
      3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0%
      vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin
      increased the risk of major bleeding. In a post hoc analysis, major bleeding was
      associated with a greater risk of subsequent acute kidney injury (23.3% when
      bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio,
      2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically
      important hypotension. In a post hoc analysis, clinically important hypotension
      was associated with a greater risk of subsequent acute kidney injury (14.3% when
      hypotension was present vs 11.8% when hypotension was absent; adjusted hazard
      ratio, 1.34; 95% CI, 1.14-1.58). CONCLUSIONS AND RELEVANCE: Among patients
      undergoing major noncardiac surgery, neither aspirin nor clonidine administered
      perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01082874.

PMID- 25399012
TI  - Levofloxacin for BK virus prophylaxis following kidney transplantation: a
      randomized clinical trial.
AB  - IMPORTANCE: BK virus infection is a significant complication of modern
      immunosuppression used in kidney transplantation. Viral reactivation occurs first
      in the urine (BK viruria) and is associated with a high risk of transplant
      failure. There are currently no therapies to prevent or treat BK virus infection.
      Quinolone antibiotics have antiviral properties against BK virus but efficacy at
      preventing this infection has not been shown in prospective controlled studies.
      OBJECTIVE: To determine if levofloxacin can prevent BK viruria in kidney
      transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo
      controlled randomized trial involving 154 patients who received a living or
      deceased donor kidney-only transplant in 7 Canadian transplant centers between
      December 2011 and June 2013. INTERVENTIONS: Participants were randomly assigned
      to receive a 3-month course of levofloxacin (500 mg/d; n = 76) or placebo (n =
      78) starting within 5 days after transplantation. MAIN OUTCOMES AND MEASURES: The
      primary outcome was time to occurrence of BK viruria (detected using quantitative
      real-time polymerase chain reaction) within the first year after transplantation.
      Secondary outcomes included BK viremia, peak viral load, rejection, and patient
      and allograft survival. RESULTS: The mean follow-up time was 46.5 weeks in the
      levofloxacin group and 46.3 weeks in the placebo group (27 patients had follow-up
      terminated before the end of the planned follow-up period or development of
      viruria because the trial was stopped early owing to lack of funding). BK viruria
      occurred in 22 patients (29%) in the levofloxacin group and in 26 patients
      (33.3%) in the placebo group (hazard ratio, 0.91; 95% CI, 0.51-1.63; P = .58).
      There was no significant difference between the 2 groups in regard to any of the
      secondary end points. There was an increased risk of resistant infection among
      isolates usually sensitive to quinolones in the levofloxacin group vs placebo
      (14/24 [58.3%] vs 15/45 [33.3%], respectively; risk ratio, 1.75; 95% CI, 1.01
      2.98) as well as a nonsignificant increased risk of suspected tendinitis (6/76
      [7.9%] vs 1/78 [1.3%]; risk ratio, 6.16; 95% CI, 0.76-49.95). CONCLUSIONS AND
      RELEVANCE: Among kidney transplant recipients, a 3-month course of levofloxacin
      initiated early following transplantation did not prevent BK viruria.
      Levofloxacin was associated with an increased risk of adverse events such as
      bacterial resistance. These findings do not support the use of levofloxacin to
      prevent posttransplant BK virus infection. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01353339.

PMID- 25399013
TI  - Reporting child language sampling procedures.
AB  - PURPOSE: Despite the long history of language sampling use in the study of child
      language development and disorders, there are no set guidelines specifying the
      reporting of language sampling procedures. The authors propose reporting
      standards for use by investigators who employ language samples in their research.
      METHOD: The authors conducted a literature search of child-focused studies
      published in journals of the American Speech-Language-Hearing Association between
      January 2000 and December 2011 that included language sampling procedures to help
      characterize child participants or to derive measures to serve as dependent
      variables. Following this search, they reviewed each study and documented the
      language sampling procedures reported. RESULTS: The authors' synthesis revealed
      that approximately 25% of all child-focused studies use language samples to help
      characterize participants and/or derive dependent variables. They found
      remarkable inconsistencies in the reporting of language sampling procedures.
      CONCLUSION: To maximize the conclusions drawn from research using language
      samples, the authors strongly encourage investigators of child language to
      consistently report language sampling procedures using the proposed reporting
      checklist.

PMID- 25399014
TI  - Prevention of acute kidney injury using vasoactive or antiplatelet treatment:
      three strikes and out?

PMID- 25399015
TI  - Eroding students' rural motivation: first do no harm?
AB  - Migration of health professionals is one of the drivers of vast inequalities in
      access to healthcare, as medical graduates tend to move away from both poorer
      countries and rural areas. One of the central ethical problems raised in
      attempting to alleviate these inequalities is the tension between the healthcare
      needs of under-served patients and the rights of medical graduates to choose
      their place of work and specialty. If medical graduates had greater motivation to
      work in under-served rural areas, this tension would decrease accordingly.
      Medical schools have a duty to avoid eroding existing motivation for such
      training and practice. This duty has practical implications. Medical students'
      motivation regarding their choice of specialty changes during medical training,
      turning them away from choices such as primary care and rural practice towards
      more highly specialised, more hospital based specialties. Although students may
      be victims of a number of biases in the initial assessment, this is unlikely to
      be the whole story. Students' priorities are likely to change based on their
      admiration for specialist role models and the visibility of the financial and non
      financial rewards attached to these specialties. Students may also have a false
      expectation upon admission that they will be proficient in rural medicine on
      graduation, and change their mind once they realise the limits of their skills in
      that area. Although the measures required to reverse this effect currently lack a
      solid evidence base, they are plausible and supported by the available data. 

PMID- 25399016
TI  - Optimal number of days for home blood pressure measurement.
AB  - BACKGROUND: Current guidelines make no outcome-based recommendations on the
      optimal measurement schedule for home blood pressure (BP). METHODS: We enrolled
      4,802 randomly recruited participants from three populations. The participants
      were classified by their (i) cross-classification according to office and home BP
      (normotension, masked hypertension, white-coat hypertension, and sustained
      hypertension) and (ii) home BP level (normal BP, high normal BP, grade 1 and 2
      hypertension), while the number of home measurement days was increased from 1 to
      7. The prognostic accuracy of home BP with an increasing number of home BP
      measurement days was also assessed by multivariable-adjusted Cox models. RESULTS:
      Agreement in classification between consecutive measurement days indicated near
      perfect agreement (kappa >= 0.9) after the sixth measurement day for both office
      and home BP cross-classification (97.8% maintained classification, kappa = 0.97)
      and home BP level (93.6% maintained classification, kappa = 0.91). Over a follow
      up of 8.3 years, 568 participants experienced a cardiovascular event, and the
      first home BP measurement alone predicted events significantly (P <= 0.003). The
      confidence intervals (CIs) were too wide and overlapping to show superiority of
      multiple measurement days over the first measurement day (hazard ratios per 10mm
      Hg increase in systolic BP at initial day, 1.11 [CI 1.07-1.16]; that at 1-7 days,
      1.18 [CI 1.12-1.24]). Masked hypertension, but not white-coat hypertension, was
      associated with increased cardiovascular risk, irrespective of the number of home
      measurement days. CONCLUSION: Even a single home BP measurement is a potent
      predictor of cardiovascular events, whereas seven home measurement days may be
      needed to reliably diagnose hypertension.

PMID- 25399017
TI  - Prediction of cardiovascular and all-cause mortality at 10 years in the
      hypertensive aged population.
AB  - BACKGROUND: We have previously developed a score for predicting cardiovascular
      events in the intermediate term in an elderly hypertensive population. In this
      study, we aimed to extend this work to predict 10-year cardiovascular and all
      cause mortality in the hypertensive aged population. METHODS: Ten-year follow-up
      data of 5,378 hypertensive participants in the Second Australian National Blood
      Pressure study who were aged 65-84 years at baseline (1995-2001) and without
      prior cardiovascular events were analyzed. By using bootstrap resampling variable
      selection methods and comparing the Akaike and Bayesian information criterion and
      C-indices of the potential models, optimal and parsimonious multivariable Cox
      proportional hazards models were developed to predict 10-year cardiovascular and
      all-cause mortality. The models were validated using bootstrap validation method
      internally and using the Dubbo Study dataset externally. RESULTS: The final model
      for cardiovascular mortality included detrimental (age, smoking, diabetes, waist
      hip ratio, and disadvantaged socioeconomic status) and protective factors (female
      sex, alcohol consumption, and physical activity). The final model for all-cause
      mortality also included detrimental (age, smoking, random blood glucose, and
      disadvantaged socioeconomic status) and protective factors (female sex, alcohol
      consumption, body mass index, and statin use). Blood pressure did not appear in
      either model in this patient group. The C-statistics for internal validation were
      0.707 (cardiovascular mortality) and 0.678 (all-cause mortality), and for
      external validation were 0.729 (cardiovascular mortality) and 0.772 (all-cause
      mortality). CONCLUSIONS: These algorithms allow reliable estimation of 10-year
      risk of cardiovascular and all-cause mortality for hypertensive aged individuals.

PMID- 25399018
TI  - Overexpression of the PP2A regulatory subunit Tap46 leads to enhanced plant
      growth through stimulation of the TOR signalling pathway.
AB  - Tap46, a regulatory subunit of protein phosphatase 2A (PP2A), plays an essential
      role in plant growth and development through a functional link with the Target of
      Rapamycin (TOR) signalling pathway. Here, we have characterized the molecular
      mechanisms behind a gain-of-function phenotype of Tap46 and its relationship with
      TOR to gain further insights into Tap46 function in plants. Constitutive
      overexpression of Tap46 in Arabidopsis resulted in overall growth stimulation
      with enlarged organs, such as leaves and siliques. Kinematic analysis of leaf
      growth revealed that increased cell size was mainly responsible for the leaf
      enlargement. Tap46 overexpression also enhanced seed size and viability under
      accelerated ageing conditions. Enhanced plant growth was also observed in
      dexamethasone (DEX)-inducible Tap46 overexpression Arabidopsis lines, accompanied
      by increased cellular activities of nitrate-assimilating enzymes. DEX-induced
      Tap46 overexpression and Tap46 RNAi resulted in increased and decreased
      phosphorylation of S6 kinase (S6K), respectively, which is a sensitive indicator
      of endogenous TOR activity, and Tap46 interacted with S6K in planta based on
      bimolecular fluorescence complementation and co-immunoprecipitation. Furthermore,
      inactivation of TOR by estradiol-inducible RNAi or rapamycin treatment decreased
      Tap46 protein levels, but increased PP2A catalytic subunit levels. Real-time
      quantitative PCR analysis revealed that Tap46 overexpression induced
      transcriptional modulation of genes involved in nitrogen metabolism, ribosome
      biogenesis, and lignin biosynthesis. These findings suggest that Tap46 modulates
      plant growth as a positive effector of the TOR signalling pathway and Tap46/PP2Ac
      protein abundance is regulated by TOR activity.

PMID- 25399019
TI  - Semi-dwarfism and lodging tolerance in tef (Eragrostis tef) is linked to a
      mutation in the alpha-Tubulin 1 gene.
AB  - Genetic improvement of native crops is a new and promising strategy to combat
      hunger in the developing world. Tef is the major staple food crop for
      approximately 50 million people in Ethiopia. As an indigenous cereal, it is well
      adapted to diverse climatic and soil conditions; however, its productivity is
      extremely low mainly due to susceptibility to lodging. Tef has a tall and weak
      stem, liable to lodge (or fall over), which is aggravated by wind, rain, or
      application of nitrogen fertilizer. To circumvent this problem, the first semi
      dwarf lodging-tolerant tef line, called kegne, was developed from an ethyl
      methanesulphonate (EMS)-mutagenized population. The response of kegne to
      microtubule-depolymerizing and -stabilizing drugs, as well as subsequent gene
      sequencing and segregation analysis, suggests that a defect in the alpha-Tubulin
      gene is functionally and genetically tightly linked to the kegne phenotype. In
      diploid species such as rice, homozygous mutations in alpha-Tubulin genes result
      in extreme dwarfism and weak stems. In the allotetraploid tef, only one
      homeologue is mutated, and the presence of the second intact alpha-Tubulin gene
      copy confers the agriculturally beneficial semi-dwarf and lodging-tolerant
      phenotype. Introgression of kegne into locally adapted and popular tef cultivars
      in Ethiopia will increase the lodging tolerance in the tef germplasm and, as a
      result, will improve the productivity of this valuable crop. 

PMID- 25399020
TI  - Functional inactivation of UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1)
      induces early leaf senescence and defence responses in rice.
AB  - Plant leaf senescence and defence responses are important biological processes,
      but the molecular mechanisms involved are not well understood. This study
      identified a new rice mutant, spotted leaf 29 (spl29). The SPL29 gene was
      identified by map-based cloning, and SPL29 was confirmed as UDP-N
      acetylglucosamine pyrophosphorylase 1 (UAP1) by enzymatic analysis. The mutant
      spl29 lacks UAP activity. The biological phenotypes for which UAP is responsible
      have not previously been reported in plants. The spl29 mutant displayed early
      leaf senescence, confirmed by chlorophyll loss and photosystem II decline as
      physiological indicators, chloroplast degradation as a cellular characteristic,
      and both upregulation of senescence transcription factors and senescence
      associated genes, and downregulation of photosynthesis-related genes, as
      molecular evidence. Defence responses were induced in the spl29 mutant, shown by
      enhanced resistance to bacterial blight inoculation and upregulation of defence
      response genes. Reactive oxygen species, including O2 (-) and H2O2, accumulated
      in spl29 plants; there was also increased malondialdehyde content. Enhanced
      superoxide dismutase activity combined with normal catalase activity in spl29
      could be responsible for H2O2 accumulation. The plant hormones jasmonic acid and
      abscisic acid also accumulated in spl29 plants. ROS and plant hormones probably
      play important roles in early leaf senescence and defence responses in the spl29
      mutant. Based on these findings, it is suggested that UAP1 is involved in
      regulating leaf senescence and defence responses in rice. 

PMID- 25399021
TI  - Health & demographic surveillance system profile: the Nahuche Health and
      Demographic Surveillance System, Northern Nigeria (Nahuche HDSS).
AB  - The Nahuche Health and Demographic Surveillance System (HDSS) study site,
      established in 2009 with 137 823 individuals is located in Zamfara State, north
      western Nigeria. North-West Nigeria is a region with one of the worst maternal
      and child health indicators in Nigeria. For example, the 2013 Nigeria Demographic
      and Health Survey estimated an under-five mortality rate of 185 deaths per 1000
      live births for the north-west geo-political zone compared with a national
      average of 128 deaths per 1000 live births. The site comprises over 100 villages
      under the leadership of six district heads. Virtually all the residents of the
      catchment population are Hausa by ethnicity. After a baseline census in 2010,
      regular update rounds of data collection are conducted every 6 months. Data
      collection on births, deaths, migration events, pregnancies, marriages and
      marriage termination events are routinely conducted. Verbal autopsy (VA) data are
      collected on all deaths reported during routine data collection. Annual update
      data on antenatal care and household characteristics are also collected.
      Opportunities for collaborations are available at Nahuche HDSS. The Director of
      Nahuche HDSS, M.O. Oche at [ochedr@hotmail.com] is the contact person for all
      forms of collaboration. 

PMID- 25399022
TI  - Alternative medicine: an update on cupping therapy.
AB  - To know the research progress of cupping therapy all over the world, the authors
      analyze the research of cupping therapy in recent 5 years. It indicates that
      cupping therapy can be applied to extensive curable disease, but has poor
      clinical evidence. Some improvements in the mechanism research of cupping therapy
      have been made, but it needs further research. The adverse events of cupping
      therapy attract attention. The standardization of cupping therapy has emerged. 

PMID- 25399023
TI  - How and why does the areole meristem move in Echinocereus (Cactaceae)?
AB  - BACKGROUND AND AIMS: In Cactaceae, the areole is the organ that forms the leaves,
      spines and buds. Apparently, the genus Echinocereus develops enclosed buds that
      break through the epidermis of the stem adjacent to the areole; this trait most
      likely represents a synapomorphy of Echinocereus. The development of the areole
      is investigated here in order to understand the anatomical modifications that
      lead to internal bud development and to supplement anatomical knowledge of plants
      that do not behave according to classical shoot theory. METHODS: The external
      morphology of the areole was documented and the anatomy was studied using tissue
      clearing, scanning electron microscopy and light microscopy for 50 species that
      represent the recognized clades and sections of the traditional classification of
      the genus, including Morangaya pensilis (Echinocereus pensilis). KEY RESULTS: In
      Echinocereus, the areole is sealed by the periderm, and the areole meristem is
      moved and enclosed by the differential growth of the epidermis and surrounding
      cortex. The enclosed areole meristem is differentiated in a vegetative or floral
      bud, which develops internally and breaks through the epidermis of the stem. In
      Morangaya pensilis, the areole is not sealed by the periderm and the areole
      meristem is not enclosed. CONCLUSIONS: The enclosed areole meristem and internal
      bud development are understood to be an adaptation to protect the meristem and
      the bud from low temperatures. The anatomical evidence supports the hypothesis
      that the enclosed bud represents one synapomorphy for Echinocereus and also
      supports the exclusion of Morangaya from Echinocereus.

PMID- 25399024
TI  - In situ analysis of foliar zinc absorption and short-distance movement in fresh
      and hydrated leaves of tomato and citrus using synchrotron-based X-ray
      fluorescence microscopy.
AB  - BACKGROUND AND AIMS: Globally, zinc deficiency is one of the most important
      nutritional factors limiting crop yield and quality. Despite widespread use of
      foliar-applied zinc fertilizers, much remains unknown regarding the movement of
      zinc from the foliar surface into the vascular structure for translocation into
      other tissues and the key factors affecting this diffusion. METHODS: Using
      synchrotron-based X-ray fluorescence microscopy (u-XRF), absorption of foliar
      applied zinc nitrate or zinc hydroxide nitrate was examined in fresh leaves of
      tomato (Solanum lycopersicum) and citrus (Citrus reticulatus). KEY RESULTS: The
      foliar absorption of zinc increased concentrations in the underlying tissues by
      up to 600-fold in tomato but only up to 5-fold in citrus. The magnitude of this
      absorption was influenced by the form of zinc applied, the zinc status of the
      treated leaf and the leaf surface to which it was applied (abaxial or adaxial).
      Once the zinc had moved through the leaf surface it appeared to bind strongly,
      with limited further redistribution. Regardless of this, in these underlying
      tissues zinc moved into the lower-order veins, with concentrations 2- to 10-fold
      higher than in the adjacent tissues. However, even once in higher-order veins,
      the movement of zinc was still comparatively limited, with concentrations
      decreasing to levels similar to the background within 1-10 mm. CONCLUSIONS: The
      results advance our understanding of the factors that influence the efficacy of
      foliar zinc fertilizers and demonstrate the merits of an innovative methodology
      for studying foliar zinc translocation mechanisms.

PMID- 25399025
TI  - Early intervention: how early and with what?

PMID- 25399027
TI  - mimicMe: a web server for prediction and analysis of host-like proteins in
      microbial pathogens.
AB  - SUMMARY: mimicMe is a web server for prediction and analysis of host-like
      proteins (mimics) encoded by microbial pathogens. Users select a host species and
      any set of pathogen and control proteomes (bacterial, fungal, protozoan or viral)
      and mimicMe reports host-like proteins that are unique to or enriched among
      pathogens. Additional server features include visualization of structural
      similarities between pathogen and host proteins as well as function-enrichment
      analysis. AVAILABILITY AND IMPLEMENTATION: mimicMe is available at
      http://mimicme.uwaterloo.ca CONTACT: acdoxey@uwaterloo.ca.

PMID- 25399026
TI  - Are Negative Symptoms Dimensional or Categorical? Detection and Validation of
      Deficit Schizophrenia With Taxometric and Latent Variable Mixture Models.
AB  - Studies have supported the validity of the deficit form of schizophrenia (ie,
      people with primary and enduring negative symptoms). A test of whether that group
      is a true taxon-that is, a distinct, discontinuous group-has yet to be conducted
      and the underlying structure of negative symptoms as categorical or dimensional
      remains undetermined. The present study examined the latent structure of negative
      and deficit symptoms to determine if a nonarbitrary boundary distinguishes
      deficit from nondeficit forms of schizophrenia (ie, whether these symptoms
      reflect a continuous or categorical variable). Schedule for the Deficit Syndrome
      ratings of 789 individuals with a psychotic disorder were submitted to taxometric
      and latent variable mixture analyses to test categorical vs dimensional
      hypotheses of negative symptoms and deficit schizophrenia. Analytic models
      favored a taxonic structure of negative symptoms and the validity of the
      deficit/nondeficit classification scheme. Taxometric classification outperformed
      clinician-based deficit/nondeficit classification in its association with summer
      birth, male sex, premorbid adjustment, neurocognition, and psychosocial
      functioning. Within taxon and complement classes, severity scores remained
      significant predictors of premorbid adjustment, neurocognition, and psychosocial
      functioning. Thus, although a categorical approach is validated, a hybrid
      categorical-dimensional conceptualization of negative symptoms also has validity
      for the prediction of external variables. 

PMID- 25399028
TI  - SYSBIONS: nested sampling for systems biology.
AB  - MOTIVATION: Model selection is a fundamental part of the scientific process in
      systems biology. Given a set of competing hypotheses, we routinely wish to choose
      the one that best explains the observed data. In the Bayesian framework, models
      are compared via Bayes factors (the ratio of evidences), where a model's evidence
      is the support given to the model by the data. A parallel interest is inferring
      the distribution of the parameters that define a model. Nested sampling is a
      method for the computation of a model's evidence and the generation of samples
      from the posterior parameter distribution. RESULTS: We present a C-based, GPU
      accelerated implementation of nested sampling that is designed for biological
      applications. The algorithm follows a standard routine with optional extensions
      and additional features. We provide a number of methods for sampling from the
      prior subject to a likelihood constraint. AVAILABILITY AND IMPLEMENTATION: The
      software SYSBIONS is available from
      http://www.theosysbio.bio.ic.ac.uk/resources/sysbions/ CONTACT:
      m.stumpf@imperial.ac.uk, robert.johnson11@imperial.ac.uk.

PMID- 25399029
TI  - E-MEM: efficient computation of maximal exact matches for very large genomes.
AB  - MOTIVATION: Alignment of similar whole genomes is often performed using anchors
      given by the maximal exact matches (MEMs) between their sequences. In spite of
      significant amount of research on this problem, the computation of MEMs for large
      genomes remains a challenging problem. The leading current algorithms employ full
      text indexes, the sparse suffix array giving the best results. Still, their
      memory requirements are high, the parallelization is not very efficient, and they
      cannot handle very large genomes. RESULTS: We present a new algorithm, efficient
      computation of MEMs (E-MEM) that does not use full text indexes. Our algorithm
      uses much less space and is highly amenable to parallelization. It can compute
      all MEMs of minimum length 100 between the whole human and mouse genomes on a 12
      core machine in 10 min and 2 GB of memory; the required memory can be as low as
      600 MB. It can run efficiently genomes of any size. Extensive testing and
      comparison with currently best algorithms is provided. AVAILABILITY AND
      IMPLEMENTATION: The source code of E-MEM is freely available at:
      http://www.csd.uwo.ca/~ilie/E-MEM/ CONTACT: ilie@csd.uwo.ca SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25399030
TI  - CaMKII: the Swiss army knife of synaptic plasticity.

PMID- 25399031
TI  - Is cooking at home associated with better diet quality or weight-loss intention?
AB  - OBJECTIVE: To examine national patterns in cooking frequency and diet quality
      among adults in the USA, overall and by weight-loss intention. DESIGN: Analysis
      of cross-sectional 24 h dietary recall and interview data. Diet quality measures
      included total kilojoules per day, grams of fat, sugar and carbohydrates per day,
      fast-food meals per week, and frozen/pizza and ready-to-eat meals consumed in the
      past 30 d. Multivariable regression analysis was used to test associations
      between frequency of cooking dinner per week (low (0-1), medium (2-5) and high (6
      7)), dietary outcomes and weight-loss intention. SETTING: The 2007-2010 National
      Health and Nutrition Examination Survey. SUBJECTS: Adults aged 20 years and over
      (n 9569). RESULTS: In 2007-2010, 8 % of adults lived in households in which
      someone cooked dinner 0-1 times/week and consumed, on an average day, 9627 total
      kilojoules, 86 g fat and 135 g sugar. Overall, compared with low cookers (0-1
      times/week), a high frequency of cooking dinner (6-7 times/week) was associated
      with lower consumption of daily kilojoules (9054 v. 9627 kJ, P=0.002), fat (81 v.
      86 g, P=0.016) and sugar (119 v. 135 g, P<0.001). Individuals trying to lose
      weight consumed fewer kilojoules than those not trying to lose weight, regardless
      of household cooking frequency (2111 v. 2281 kJ/d, P<0.006). CONCLUSIONS: Cooking
      dinner frequently at home is associated with consumption of a healthier diet
      whether or not one is trying to lose weight. Strategies are needed to encourage
      more cooking among the general population and help infrequent cookers better
      navigate the food environment outside the home.

PMID- 25399032
TI  - HIV prevalence and risk behaviors among people who inject drugs in two serial
      cross-sectional respondent-driven sampling surveys, Zanzibar 2007 and 2012.
AB  - People who inject drugs (PWID) are at higher risk of acquiring HIV due to risky
      injection and sexual practices. We measured HIV prevalence and behaviors related
      to acquisition and transmission risk at two time points (2007 and 2012) in
      Zanzibar, Tanzania. We conducted two rounds of behavioral and biological
      surveillance among PWID using respondent-driven sampling, recruiting 499 and 408
      PWID, respectively. Through faceto- face interviews, we collected information on
      demographics as well as sexual and injection practices. We obtained blood samples
      for biological testing. We analyzed data using RDSAT and exported weights into
      STATA for multivariate analysis. HIV prevalence among sampled PWID in Zanzibar
      was 16.0 % in 2007 and 11.3 % in 2012; 73.2 % had injected drugs for 7 years or
      more in 2007, while in the 2012 sample this proportion was 36.9 %. In 2007, 53.6
      % reported having shared a needle in the past month, while in the 2012 sample,
      29.1 % reported having done so. While 13.3 % of PWID in 2007 reported having been
      tested for HIV infection and received results in the past year, this proportion
      was 38.0 % in 2012. Duration of injection drug use for 5 years or more was
      associated with higher odds of HIV infection in both samples. HIV prevalence and
      indicators of risk and preventive behaviors among PWID in Zanzibar were generally
      more favorable in 2012 compared to 2007-a period marked by the scale-up of
      prevention programs focusing on PWID. While encouraging, causal interpretation
      needs to be cautious and consider possible sample differences in these two cross
      sectional surveys. HIV prevalence and related risk behaviors persist at levels
      warranting sustained and enhanced efforts of primary prevention and harm
      reduction.

PMID- 25399033
TI  - Abuse Impedes Prevention: The Intersection of Intimate Partner Violence and
      HIV/STI Risk Among Young African American Women.
AB  - Intimate partner violence (IPV) is associated with risky sexual behavior and STIs
      among diverse groups of women. IPV was examined as a moderator of efficacy for an
      HIV/STI intervention. 848 African American women, 18-29, were randomly assigned
      to an HIV/STI intervention or control condition. Participants completed measures
      on sociodemographics, IPV, risky sexual behavior and received STI testing. IPV
      predicted inconsistent condom use and a risky sexual partner over 12-month follow
      up. A significant interaction indicated that among women who experienced IPV,
      those in the intervention were more likely to test positive for Trichomonas
      vaginalis (TV). Among intervention participants, those who experienced IPV were
      more likely to test TV-positive than those who did not. In an HIV intervention
      that did not specifically address IPV, women in the control condition were less
      likely to acquire TV than those in the intervention. Consideration of
      contextual/interpersonal factors is essential when developing HIV intervention
      programs. 

PMID- 25399035
TI  - Ebola, should we be concerned?

PMID- 25399034
TI  - Association of Markers of Inflammation with Sleep and Physical Activity Among
      People Living with HIV or AIDS.
AB  - This study examined associations of sleep and minutes spent in moderate-vigorous
      physical activity (MVPA) with C-reactive protein (CRP) and interleukin (IL)-6
      among persons living with HIV. Cross-sectional analyses (n = 45) focused on
      associations of inflammatory outcomes (i.e., CRP and IL-6) with actigraph-derived
      sleep duration, latency, and efficiency; sleep onset; wake time; and wake-after
      sleep-onset; as well as MVPA. Least square means for CRP and IL-6 by levels of
      sleep and MVPA were computed from general linear models. Individuals below the
      median of sleep duration, above the median for sleep onset, and below the median
      of MVPA minutes had higher CRP or IL-6 levels. Generally, individuals with both
      low MVPA and poor sleep characteristics had higher inflammation levels than those
      with more MVPA and worse sleep. Understanding the combined impact of multiple
      lifestyle/behavioral factors on inflammation could inform intervention strategies
      to reduce inflammation and therefore, chronic disease risk.

PMID- 25399036
TI  - Treating recurrent mood disorders seriously.

PMID- 25399037
TI  - Children's participation in society is likely to lead to their improved health
      and wellbeing.

PMID- 25399038
TI  - Patient engagement with primary health care following discharge from community
      mental health services.
AB  - AIM: Increasing pressure is being placed to facilitate Community Mental Health
      (CMH) patients' discharge to primary care. However, engagement following
      discharge is an under-researched area. This audit aimed to measure engagement and
      explore the factors that are associated with engagement in primary care following
      discharge from CMH. METHOD: Primary care teams for 55 service users discharged
      from Auckland District Health Board CMH centres between July and December 2012
      were approached as part of an audit and asked to provide information regarding
      engagement with general practitioners. RESULTS: From the 50 responses received,
      the median number of GP visits per year was 3.7 and the mean was 4.41. 72% of the
      sample had contact with their GP at least every 3-4 months, however 8% did not
      engage with their primary care team. Differences in attendance following
      discharge based on age, diagnosis or socioeconomic status were not found. There
      was a suggestion that where GPs had responsibility for ongoing prescribing
      individuals engaged more frequently. CONCLUSION: Generally, discharged
      individuals engage with their primary care team well, and at a level many
      clinicians would be comfortable with. There is a proportion of the population
      that does not engage at this level, which requires further study.

PMID- 25399039
TI  - Children's voices in public hospital healthcare delivery: intention as opposed to
      practice.
AB  - AIM: To determine the extent to which children have the opportunity to provide
      feedback on public hospital care in New Zealand. METHOD: A scan of the web sites
      of the Ministry of Health and the Health Quality and Safety Commission New
      Zealand (HQSC) together with a search of core District Health Board publications
      was conducted to identify existing or planned processes to capture the hospital
      experience of patients under 18 years. RESULTS: The importance of gathering
      patient feedback was recognised but, currently, ad hoc strategies are being used
      to put these good intentions into practice. Although some DHBs are introducing
      novel methods of gathering patient feedback, details of data collection methods
      and characteristics of participants are often not publicised. The HQSC has
      developed an adult Inpatient survey to provide a coherent means of assessing
      patient experience nationally but there is currently no children's survey
      available. CONCLUSIONS: Our analysis suggests a lack of opportunity for
      children's perspectives to be taken into account in secondary health service
      delivery. The current 'paternalistic' approach, based upon children being a
      vulnerable population, is contrary to the emerging recognition that children are
      individuals who can contribute to their own care and well-being.

PMID- 25399040
TI  - Can patient safety indicators monitor medical and surgical care at New Zealand
      public hospitals?
AB  - INTRODUCTION: Increasing interest has focused on the safety of hospital care. The
      AusPSIs are a set of indicators developed from Australian administrative data to
      reliably identify inpatient adverse events in hospitals. The main aim of this
      study was to explore the application of the AHRQ/AusPSIs to New Zealand
      administrative hospital data related to medical and surgical care. Variation over
      time and across hospitals were also considered for a subset of the more common
      indicators. METHOD: AHRQ/AusPSIs were adapted for use with New Zealand National
      Minimum Dataset administrative data for the period 2001-9. Crude positive event
      rates for each of the 16 indicators were assessed across New Zealand public
      hospitals. Variation over time for six more common indicators is presented using
      statistical control charts. Variation between hospitals was explored using rates
      adjusted for differences in patient variables including age, sex, ethnicity,
      rurality of residence, NZDep score and comorbidities. RESULTS: The AHRQ/AusPSIs
      were applied to New Zealand administrative hospital data and some 99,366
      admissions were associated with a positive indicator event. However rates for
      some indicators were low (<1% of denominator admissions). Over the study period
      considerable variation in the rate of positive events was evident for the six
      most common indicators. Likewise there was substantial variation between
      hospitals in relation to risk adjusted positive event rates DISCUSSION: Patient
      safety indicators can be applied to New Zealand administrative hospital data.
      While infrequent rates hinder the use of some of the indicators, several could
      now be readily employed as warning flags to help monitor rates of adverse events
      at particular hospitals. In conjunction with other established or emerging tools,
      such as audit and trigger tools, the PSIs are now available to promote ongoing
      quality improvement activities in New Zealand hospitals.

PMID- 25399041
TI  - The impact of the 6-month waiting target for elective surgery: a patient record
      study.
AB  - AIM: To quantify the number of patients declined surgery due to scoring below the
      financial threshold, when presenting for total hip or total knee arthroplasty at
      two New Zealand District Health Boards (DHBs). METHOD: Data from patients
      presenting with hip or knee osteoarthritis at both Whangarei Base Hospital and
      Hawke's Bay Regional Hospital from June 2012 to June 2013 were reviewed. Data
      were taken from hospital codes and patient records. The outcome from clinic
      visits were recorded as well as the patient's New Zealand Orthopaedic Association
      (NZOA) prioritisation score. RESULTS: A total of 1202 patient records were
      reviewed: 393 from Whangarei Base Hospital and 809 from Hawke's Bay Regional
      Hospital. Of the 858 patients where surgery was both desired by the patient and
      deemed appropriate by the surgeon, 307 (36%) were declined for being below the
      financial threshold. These patients had a mean NZOA score of 66.42. At Whangarei
      Base Hospital, 300 patients were referred for surgery and 98 (33%) were declined
      for being below threshold. The mean NZOA score was significantly higher in the
      patients booked for surgery (M=70.62) compared with those declined below
      threshold (M=55.39, p<0.001). Of the 497 patients referred for arthroplasty at
      Hawke's Bay Regional Hospital, 205 (41%) were declined for being below threshold.
      The mean NZOA prioritisation scores were also significantly higher in the
      patients booked for surgery (M=76.96) compared to those declined (M=64.66; p less
      than or equal to 0.001). CONCLUSION: 36% of patients who were suitable for hip or
      knee arthroplasty were declined elective surgery for being below threshold. Many
      of these patients have significant pain and disability.

PMID- 25399042
TI  - Who wants to be a surgeon? Patterns of medical student career choice.
AB  - AIM: NZ needs a surgical workforce with the capacity to meet the increasing
      health demands of an aging population. This study determined longitudinal
      patterns of medical student interest in a surgical career and factors influencing
      that choice. METHOD: We studied medical students entering the Auckland medical
      programme from 2006-2008 who completed an entry and exit questionnaire on career
      intentions. Four notional groups were created, depending on the level of interest
      at entry and at exit. Demographic factors for each category were compared.
      Analysis of influencing factors was also undertaken. RESULTS: Of 488 students,
      310 (64%) completed both an entry and exit questionnaire. Over 50% of students
      had a strong interest in a surgical career at entry, dropping to 26% at exit. The
      'Never Evers' (No interest at entry /No interest at exit) made up 39%,'Divergers'
      (Strong/No) 35%, 'Die Hards' (Strong/Strong) 18%, and 'Convertibles' (No/Strong)
      8%. Less interest in a surgical career was seen among female (P=0.001) and older
      students (P=0.017). Influencing factors differentiating the 'Die Hards' from the
      'Divergers' were work hours and flexibility (less influence among 'Die Hards'),
      with procedural nature and consultants/mentors (higher). CONCLUSION: There is a
      significant reduction in interest in a surgical career over the course of the
      undergraduate programme, especially among female and older students. Yet the
      level appears sufficient for available training places. Consultant role models
      are an important career influence. Lack of flexibility in work and training
      programmes continue to provide challenges in creating a diverse surgical
      workforce.

PMID- 25399043
TI  - Agreement of clinical measurements of liver size with ultrasound when performed
      by medical students.
AB  - AIM: The accuracy of physical examination techniques in detecting liver disease
      is unclear. We sought to determine the perceived location of the lower liver
      border via scratch, percussion, palpation and ballottement with novice medical
      student examiners, compared with ultrasound localisation. METHOD: Five novice
      medical students learnt four liver examination techniques and measured the lower
      liver border in 19 healthy volunteers. The difference between the examination
      technique and ultrasound (bias) and limits of agreement of each method were
      estimated by mixed linear models and shown using Bland-Altman- like plots.
      RESULTS: All techniques had similar bias for the lower liver border, between 1.6
      and 1.9 cm superior to the ultrasound measurement. Percussion had the smallest
      variability with increasing liver size. Limits of agreement were wide for all
      techniques, smallest for palpation (6.04 cm) and largest for scratch (7.2 cm)
      compared to the mean liver distance of 8 cm. Conclusion There was no difference
      in bias between the scratch, percussion, palpation and ballottement techniques
      regarding the lower liver border. All techniques had very wide limits of
      agreement, although palpation had the smallest. Liver size examination by novice
      medical students in healthy subjects is unreliable. Further research is needed
      using examiners with a different level of expertise and participants of varying
      body habitus and confirmed liver disease.

PMID- 25399044
TI  - Fitness to practice of medical graduates: one programme's approach.
AB  - AIM: Doctors must ensure they are fit to practise medicine. There is a
      relationship between unprofessional behaviour at medical school and in subsequent
      medical practice. This study describes one programme's Fitness to Practice (FtP)
      policy and outcomes since inception in 2005. METHOD: FtP notifications were
      classified into: health or personal; professional attitudes, or external issues.
      Seriousness was classified as non-critical, critical or extraordinarily critical.
      Anonymous data were extracted and analysed from a confidential FtP database.
      RESULTS: There were 157 FtP notifications involving 132 (5.5%) students. 87.2%
      were for issues with professional attitudes and 80.3% were non-critical. 17
      students received more than one FtP notification. Students in clinical years were
      over-represented (p<0.0001) as were males (57% vs. 43%: p=0.0286). 96% of
      students continued the programme after remedial action. Two students were
      excluded from the programme on FtP grounds. The national regulatory body was
      notified of nine individual students with the potential for on- going FtP
      concerns. CONCLUSION: Over 9 years, 5.5% of medical students received a FtP
      notification, with most of these isolated non-critical incidents of a
      professional nature. A small subset of students had repeated or serious concerns,
      underscoring the need for a FtP policy in any medical programme.

PMID- 25399045
TI  - Ethics of mitochondrial therapy for deafness.
AB  - Mitochondrial therapy may provide the relief to many families with inherited
      mitochondrial diseases. However, it also has the potential for use in non-fatal
      disorders such as inherited mitochondrial deafness, providing an option for
      correction of the deafness using assisted reproductive technology. In this paper
      we discuss the potential for use in correcting mitochondrial deafness and
      consider some of the issues for the deaf community. 

PMID- 25399046
TI  - Is delirium sensitive to socioeconomic inequality?

PMID- 25399047
TI  - Duplication of inferior vena cava: a rare but clinically significant anatomical
      variation.

PMID- 25399048
TI  - The effect on knee-joint load of instruction in analgesic use compared with
      neuromuscular exercise in patients with knee osteoarthritis: study protocol for a
      randomized, single-blind, controlled trial (the EXERPHARMA trial).
AB  - BACKGROUND: Knee osteoarthritis (OA) is a mechanically driven disease, and it is
      suggested that medial tibiofemoral knee-joint load increases with pharmacologic
      pain relief, indicating that pharmacologic pain relief may be positively
      associated with disease progression. Treatment modalities that can both relieve
      pain and reduce knee-joint load would be preferable. The knee-joint load is
      influenced by functional alignment of the trunk, pelvis, and lower-limb segments
      with respect to the knee, as well as the ground-reaction force generated during
      movement. Neuromuscular exercise can influence knee load and decrease knee pain.
      It includes exercises to improve balance, muscle activation, functional
      alignment, and functional knee stability. The primary objective of this
      randomized controlled trial (RCT) is to investigate the efficacy of a
      NEuroMuscular EXercise (NEMEX) therapy program, compared with optimized
      analgesics and antiinflammatory drug use, on the measures of knee-joint load in
      people with mild to moderate medial tibiofemoral knee osteoarthritis.
      METHOD/DESIGN: One hundred men and women with mild to moderate medial knee
      osteoarthritis will be recruited from general medical practices and randomly
      allocated (1:1) to one of two 8-week treatments, either (a) NEMEX therapy twice a
      week or (b) information on the recommended use of analgesics and antiinflammatory
      drugs (acetaminophen and oral NSAIDs) via a pamphlet and video materials. The
      primary outcome is change in knee load during walking (the Knee Index, a
      composite score of the first external peak total reaction moment on the knee
      joint from all three planes based on 3D movement analysis) after 8 weeks of
      intervention. Secondary outcomes include changes in the external peak knee
      adduction moment and impulse and functional performance measures, in addition to
      changes in self-reported pain, function, health status, and quality of life.
      DISCUSSION: These findings will help determine whether 8 weeks of neuromuscular
      exercise is superior to optimized use of analgesics and antiinflammatory drugs
      regarding knee-joint load, pain and physical function in people with mild to
      moderate knee osteoarthritis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01638962 (July 3, 2012).

PMID- 25399049
TI  - Age-related DNA methylation changes for forensic age-prediction.
AB  - There is no available method of age-prediction for biological samples. The
      accumulating evidences indicate that DNA methylation patterns change with age.
      Aging resembles a developmentally regulated process that is tightly controlled by
      specific epigenetic modifications and age-associated methylation changes exist in
      human genome. In this study, three age-related methylation fragments were
      isolated and identified in blood of 40 donors. Age-related methylation changes
      with each fragment was validated and replicated in a general population sample of
      65 donors over a wide age range (11-72 years). Methylation of these fragments is
      linearly correlated with age over a range of six decades (r = 0.80-0.88). Using
      average methylation of CpG sites of three fragments, a regression model that
      explained 95 % of the variance in age was built and is able to predict an
      individual's age with great accuracy (R (2 )= 0.93). The predicted value is
      highly correlated with the observed age in the sample (r = 0.96) and has great
      accuracy of average 4 years difference between predicted age and true age. This
      study implicates that DNA methylation can be an available biological marker of
      age-prediction. Further measurement of relevant markers in the genome could be a
      tool in routine screening to predict age of forensic biological samples. 

PMID- 25399050
TI  - Genetic and toxicologic investigation of Sudden Cardiac Death in a patient with
      Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) under cocaine and alcohol
      effects.
AB  - Cocaine and alcohol toxicity is well known, especially when simultaneously
      abused. These drugs perform both acute and chronic harmfulness, with significant
      cardiac events such as ventricular arrhythmias, tachycardia, systemic
      hypertension, acute myocardial infarction, ventricular hypertrophy, and acute
      coronary syndrome. The present report refers about a patient who died after a
      documented episode of psychomotor agitation followed by cardiac arrest. At the
      autopsy investigation, arrhythmogenic right ventricular cardiomyopathy (ARVC) was
      diagnosed and confirmed by postmortem molecular analysis revealing a mutation in
      the DSG2 gene. Postmortem toxicological analysis demonstrated a recent intake of
      cocaine, and the death was attributed to cardiac arrhythmias. The detection of
      cocaine and cocaethylene in hair samples proved chronic simultaneous intake of
      cocaine and alcohol at least in the last month. The authors discuss the role of
      these drugs and genetic predisposition of the ARVC in causing the death of the
      patient.

PMID- 25399052
TI  - Workplace Harassment and Morbidity Among US Adults: Results from the National
      Health Interview Survey.
AB  - Most research on workplace harassment originates from European
      countries.Prevalence of workplace harassment and associated morbidity has not
      been well studied in the United States. The purpose of this study was to assess
      in a sample of US workers the prevalence of workplace harassment and the
      psychological and physical health consequences of workplace harassment. The 2010
      National Health Interview Survey data were analyzed in 2014 for this study. We
      computed the prevalence of workplace harassment, assessed the demographic and
      background characteristics of victims of harassment, and tested the association
      between harassment and selected health risk factors by using logistic regression
      analysis. Statistical significance was established as p < 0.01. A total of 17,524
      adults were included in our study (51.5% females and 74.9% Whites). A little <1
      in 10 (8.1%) reported being harassed in the workplace in the past 12 months. The
      odds of harassment were significantly higher for females (OR 1.47, p <
      0.001),multiracial individuals (OR 2.30, p < 0.001), and divorced or separated
      individuals (OR 1.88, p < 0.001). Victims of harassment were significantly more
      likely to: be obese, sleep less, and smoke more. In addition, harassment was
      associated with psychosocial distress, pain disorders, work loss, bed days, and
      worsening health of employees in the past 12 months. Analysis was stratified by
      gender and distinct health risk patterns for men and women victims were observed.
      Workplace harassment in the US is associated with significant health risk factors
      and morbidity. Workplace policies and protocols can play a significant role in
      reducing harassment and the associated negative health outcomes.

PMID- 25399051
TI  - Bioinformatic analysis of the distribution of inorganic carbon transporters and
      prospective targets for bioengineering to increase Ci uptake by cyanobacteria.
AB  - Cyanobacteria have evolved a carbon-concentrating mechanism (CCM) which has
      enabled them to inhabit diverse environments encompassing a range of inorganic
      carbon (Ci: [Formula: see text] and CO2) concentrations. Several uptake systems
      facilitate inorganic carbon accumulation in the cell, which can in turn be fixed
      by ribulose 1,5-bisphosphate carboxylase/oxygenase. Here we survey the
      distribution of genes encoding known Ci uptake systems in cyanobacterial genomes
      and, using a pfam- and gene context-based approach, identify in the marine
      (alpha) cyanobacteria a heretofore unrecognized number of putative counterparts
      to the well-known Ci transporters of beta cyanobacteria. In addition, our
      analysis shows that there is a huge repertoire of transport systems in
      cyanobacteria of unknown function, many with homology to characterized Ci
      transporters. These can be viewed as prospective targets for conversion into
      ancillary Ci transporters through bioengineering. Increasing intracellular Ci
      concentration coupled with efforts to increase carbon fixation will be beneficial
      for the downstream conversion of fixed carbon into value-added products including
      biofuels. In addition to CCM transporter homologs, we also survey the occurrence
      of rhodopsin homologs in cyanobacteria, including bacteriorhodopsin, a class of
      retinal-binding, light-activated proton pumps. Because they are light driven and
      because of the apparent ease of altering their ion selectivity, we use this as an
      example of re-purposing an endogenous transporter for the augmentation of Ci
      uptake by cyanobacteria and potentially chloroplasts. 

PMID- 25399053
TI  - Directing peptide conformation with centrally positioned pre-organized dipeptide
      segments: studies of a 12-residue helix and beta-hairpin.
AB  - Secondary structure formation in oligopeptides can be induced by short nucleating
      segments with a high propensity to form hydrogen bonded turn conformations. Type
      I/III turns facilitate helical folding while type II'/I' turns favour hairpin
      formation. This principle is experimentally verified by studies of two designed
      dodecapeptides, Boc-Val-Phe-Leu-Phe-Val-Aib-Aib-Val-Phe-Leu-Phe-Val-OMe 1 and Boc
      Val-Phe-Leu-Phe-Val-(D)Pro-(L)Pro-Val-Phe-Leu-Phe-Val-OMe 2. The N- and C
      terminal flanking pentapeptide sequences in both cases are identical. Peptide 1
      adopts a largely alpha-helical conformation in crystals, with a small 310 helical
      segment at the N-terminus. The overall helical fold is maintained in methanol
      solution as evidenced by NMR studies. Peptide 2 adopts an antiparallel beta
      hairpin conformation stabilized by 6 interstrand hydrogen bonds. Key nuclear
      Overhauser effects (NOEs) provide evidence for the antiparallel beta-hairpin
      structure. Aromatic proton chemical shifts provide a clear distinction between
      the conformation of peptides 1 (helical) and 2 (beta-hairpin). The proximity of
      facing aromatic residues positioned at non-hydrogen bonding positions in the
      hairpin results in extensively ring current shifted proton resonances in peptide
      2.

PMID- 25399054
TI  - Glutamate-glutamine cycle and exchange in the placenta-fetus unit during late
      pregnancy.
AB  - The present review focuses on the physiological functions of glutamate-glutamine
      exchange involving placental amino acid transport and umbilical amino acid uptake
      in mammals (particularly in sows), with special emphasis on the associated
      regulating mechanisms. Glutamate plus glutamine are among the most abundant and
      the most utilized amino acids in fetus during late gestation. During pregnancy,
      amino acids, notably as precursors of macromolecules including proteins and
      nucleotides are involved in fetal development and growth. Amino acid
      concentrations in fetus are generally higher than in the mother. Among amino
      acids, the transport and metabolism of glutamate and glutamine during fetal
      development exhibit characteristics that clearly emphasize the importance of the
      interaction between the placenta and the fetal liver. Glutamate is quite
      remarkable among amino acids, which originate from the placenta, and is cleared
      from fetal plasma. In addition, the flux of glutamate through the placenta from
      the fetal plasma is highly correlated with the umbilical glutamate delivery rate.
      Glutamine plays a central role in fetal carbon and nitrogen metabolism and
      exhibits one of the highest fetal/maternal plasma ratio among all amino acids in
      human and other mammals. Glutamate is taken up by placenta from the fetal
      circulation and then converted to glutamine before being released back into the
      fetal circulation. Works are required on the glutamate-glutamine metabolism
      during late pregnancy in physiological and pathophysiological situations since
      such works may help to improve fetal growth and development both in humans and
      other mammals. Indeed, glutamine supplementation appears to ameliorate fetal
      growth retardation in sows and reduces preweaning mortality of piglets. 

PMID- 25399055
TI  - Polyamines are common players in different facets of plant programmed cell death.
AB  - Programmed cell death (PCD) is a process that occurs throughout the life span of
      every plant life, from initial germination of the seed to the senescence of the
      plant. It is a normal physiological milestone during the plant's developmental
      process, but it can also be induced by external factors, including a variety of
      environmental stresses and as a response to pathogen infections. Changes in the
      morphology of the nucleus is one of the most noticeable during PCD but all the
      components of the plant cell (cytoplasm, cytoskeleton and organelles) are
      involved in this fascinating process. To date, relatively little is known about
      PCD in plants, but several factors, among which polyamines (PAs) and plant growth
      regulators, have been shown to play an important role in the initiation and
      regulation of the process. The role of PAs in plant PCD appears to be
      multifaceted acting in some instances as pro-survival molecules, whereas in
      others seem to be implicated in accelerating PCD. The molecular mechanism is
      still under study. Here we present some PCD plant models, focusing on the role of
      the enzyme responsible for PA conjugation to proteins: transglutaminase (TGase),
      an enzyme linked with the process of PCD also in some animal models. The role of
      PAs and plant TGase in the senescence and PCD in flowers, leaf and the self
      incompatibility of pollen will be discussed and examined in depth. 

PMID- 25399056
TI  - Biosynthetic incorporation of the azulene moiety in proteins with high
      efficiency.
AB  - Biosynthetic incorporation of beta-(1-azulenyl)-L-alanine, an isostere of
      tryptophan, is reported using a tryptophan auxotroph expression host. The azulene
      moiety introduced this way in proteins features many attractive spectroscopic
      properties, particularly suitable for in vivo studies. 

PMID- 25399057
TI  - Evaluating velopharyngeal closure with real-time MRI.

PMID- 25399058
TI  - Relationship between dietary protein intake and the changes in creatinine
      clearance and glomerular cross-sectional area in patients with IgA nephropathy.
AB  - BACKGROUND: Dietary protein intake (PI) induces glomerular hyperfiltration and
      reduced dietary PI can be effective in preserving kidney function. However, there
      is limited information regarding the relationship between dietary PI and
      glomerular histological changes in chronic kidney disease. We investigated the
      relationship between changes in dietary PI and both the changes in creatinine
      clearance and glomerular histomorphometry in adult patients with IgA nephropathy
      (IgAN). METHODS: A total of 24 consecutive adult patients with biopsy-confirmed
      IgAN were enrolled and glomerular histomorphometric variables and clinical
      variables were investigated. The main clinical variables were differences in
      creatinine clearance (Ccr) (dCcr) and in PI (dPI) which were calculated by
      subtracting PI and Ccr values in patients on a controlled diet during
      hospitalization for kidney biopsy from the respective values in patients on daily
      diets as outpatients. These values of PI were estimated from urinary urea
      excretion measured by 24-h urine collection. The main renal histomorphometric
      variable was glomerular tuft area (GTA) (MUm(2)). RESULTS: dCcr positively
      correlated with dPI (r = 0.726, P < 0.001). GTA correlated positively with dPI (r
      = 0.556, P = 0.013). Multiple regression analysis showed that dPI was
      independently associated with both dCcr and GTA. Additionally, GTA positively
      correlated with dietary PI as outpatients (r = 0.457, P = 0.043). CONCLUSION:
      Changes in dietary PI were associated with the changes in glomerular filtration
      rate. Furthermore, histomorphometric findings suggested that a greater dietary PI
      can affect the glomerular size at the time of the initial diagnostic biopsy for
      IgAN.

PMID- 25399059
TI  - Association between serum free fatty acid levels and possible related factors in
      patients with type 2 diabetes mellitus and acute myocardial infarction.
AB  - BACKGROUND: Free fatty acids (FFAs) play importance roles in the development of
      diabetes and cardiovascular diseases. We measured serum FFA levels from type 2
      diabetes mellitus (T2DM) and acute myocardial infarction (AMI) patients and assay
      the correlation between serum FFA levels and related factors. The present study
      was undertaken to investigate a possible relation between the changes in serum
      free fatty acid concentration with acute myocardial infarction and type 2
      diabetes mellitus. METHODS: The study population consisted of 540 healthy
      individuals and 103 patients with T2DM, 59 patients with AMI and 21 volunteers.
      Serum FFAs were measured with high pressure liquid chromatography. Blood urea
      nitrogen and uric acid were measured in clinical laboratory, as were glycemic,
      lipid and blood routine parameters. We selected 242 individuals with age over 60
      years, 143 healthy individuals and 52 patients with T2DM, 47 patients with AMI
      were incorporated into three groups as control group, T2DM group and AMI group.
      Associations were analyzed with stepwise regression analysis with adjusted for
      age, sex, body mass index. RESULTS: Serum FFA levels were significantly higher in
      the age over 60 years individuals compared to 20 ~ 50 years (logFFA MUmmol/L:2.60
      +/- 0.16 vs. 2.73 +/- 0.18, P < .001) in the healthy group. We found lower FFA
      levels in the AMI compared to the T2DM and control group (2.64 +/- 0.22 vs. 2.72
      +/- 0.13&2.72 +/- 0.16, respectively, P < .05&P < 0.01) in the age over 60,
      fasting blood glucose level higher in the AMI and T2DM (5.78 +/- 1.32&7.75 +/-
      2.93 mmol/L vs. 4.90 +/- 0.47 mmol/L, P < .01&P < .001) compared with the normal
      group, HDL level (1.01 +/- 0.22&0.98 +/- 0.18 mmol/L vs.1.30 +/- 0.22 mmol/L, P <
      .001&P < .001). With stepwise regression analysis, the serum FFA levels was
      positively associated with the HDL in the control group (YlogFFA = 2.32 +
      0.33XHDL, R = 0.26, P < .01) and T2MD (YlogFFA = 2.46 + 0.27XHDL, R = 0.36, P <
      .05), AST in AMI (YlogFFA =2.24 + 0. 015XAST, R = 0.49, P < .01). CONCLUSIONS:
      Compared to control group, serum FFA levels were decreased only in AMI group,
      while HDL level was increased in both AMI and T2DM group. The serum FFA levels
      were positive association with the HDL level in both T2DM and control group, FFA
      levels were positive association with AST in AMI.

PMID- 25399060
TI  - Acute acalculous cholecystitis determining Mirizzi syndrome: case report and
      literature review.
AB  - BACKGROUND: Although Mirizzi syndrome is widely reported in literature, little is
      known about acute acalcholous cholecystitis determinig the findings of a Mirizzi
      syndrome. CASE PRESENTATION: We report a case of MRCP-confirmed Mirizzi syndrome
      in acute acalculous cholecystitis resolved by surgery. CONCLUSION: Acute
      acalcholosus cholecystitis determinig a Mirizzi Syndrome should be included in
      the Mirizzi classification as a type 1. Thus it could be useful to divide the
      type 1 in two entity (compression by stone and compression by enlarged
      gallbladder). Magnetic Resonance should be considered the preferred diagnostic
      tool in any case of Mirizzi syndrome suspicious.

PMID- 25399061
TI  - Differences in micronucleus frequency and acrylamide adduct levels with
      hemoglobin between vegetarians and non-vegetarians.
AB  - PURPOSE: Nutrients and food constituents can prevent or contribute to
      genotoxicity. In this study, the possible influence of a vegetarian/non
      vegetarian diet on genotoxic effects was investigated in 58 non-smoking healthy
      vegetarians (V) and non-vegetarians (NV), age 21-37 years from the Stockholm area
      in Sweden. METHODS: Physical activity and dietary habits were similar in both
      groups, with the exception of the intake of meat and fish. Using flow cytometry,
      we determined the formation of micronuclei (MN) in transferrin-positive immature
      peripheral blood reticulocytes (Trf-Ret) (Total: n = 53; V: n = 27; NV: n = 26).
      Dietary exposure to acrylamide was measured through hemoglobin (Hb) adducts in
      peripheral erythrocytes (Total: n = 53; V: n = 29; NV: n = 24). Hb adducts of
      both acrylamide and its genotoxic metabolite glycidamide were monitored as a
      measure of the corresponding in vivo doses. RESULTS: Our data demonstrated that
      compared with the non-vegetarians, the vegetarians exhibited lower frequencies of
      MN (fMN) in the Trf-Ret (p < 0.01, Student's t test). A multivariate analysis
      demonstrated that there was no association between the fMN and factors such as
      age, sex, intake of vitamins/minerals, serum folic acid and vitamin B12 levels,
      physical activity, and body mass index. The mean Hb adduct levels of acrylamide
      and glycidamide showed no significant differences between vegetarians and non
      vegetarians. Furthermore, there were no significant relationships between the
      adduct levels and fMN in the individuals. The ratio of the Hb adduct levels from
      glycidamide and acrylamide, however, showed a significant difference (p < 0.04)
      between the two groups. CONCLUSIONS: These data suggest that the vegetarian diet
      might be beneficial in lowering genomic instability in healthy individuals. The
      measured Hb adduct levels indicate that the total intake of acrylamide does not
      differ between the two studied groups and does not contribute to the observed
      difference in fMN, although an influence of the diet on the metabolic rates of
      acrylamide was indicated. In addition, the observed significant difference in the
      background fMN in the two groups demonstrated that the MN analysis method has a
      sensitivity applicable to the biomonitoring of human lifestyle factors.

PMID- 25399062
TI  - Association between a PD-1 gene polymorphism and antisperm antibody-related
      infertility in Iranian men.
AB  - OBJECTIVE: Programmed cell death-1 (PD-1, Pdcd1), an immunoreceptor belonging to
      the CD28/CTLA-4 family negatively regulates antigen receptor signalling by
      recruiting protein tyrosine phosphatase, SHP-2 upon interacting with either of
      two ligands, PD-L1 or PD-L2. This study investigates PD-1 gene polymorphism in
      patients with antisperm antibody-related infertility METHODS: Genotyping was
      performed by polymerase chain reaction and restriction enzyme digestion (PCR
      RFLP), this polymorphism was genotyped in 145 Iranian subjects (61 patients with
      antisperm antibody-related infertility and 84 healthy controls). RESULTS:
      Patients frequencies of the G/A genotype in comparison with healthy controls
      (38.2 % vs. 32.7 %, OR =1.21, P = 0.35) were not significantly different.
      However, G/G and A/A genotype frequencies between patients and healthy controls
      were significantly different (P = 0.042, P = 0.00001, respectively). Also, allele
      frequencies of this polymorphism were significantly different (P = 0.0012) in
      patients compared to healthy controls. CONCLUSION: According to these results,
      there is a correlation between PD-1 gene polymorphism and susceptibility to
      antisperm antibody-related infertility in our study group.

PMID- 25399063
TI  - Possible influence of menstrual cycle on lymphocyte X chromosome mosaicism.
AB  - PURPOSE: Estrogens are known to selectively influence cell proliferation.
      Physiological variations of blood hormone concentration might play a role in
      regulating the level of X chromosome aneuploidy. In this study we observed the
      percentages of X aneuploid cells in standard lymphocyte cultures from blood
      samples obtained in relation to the menstrual cycle, noting whether collection
      occurred during either the follicular or the luteal phase. METHODS: A study
      consisting of 28 women with X mosaicism and recurrent pregnancy loss, and 28 age
      matched healthy controls. Cytogenetic studies were carried out on peripheral
      blood samples according to standard procedures. RESULTS: A significant difference
      in the percentage of X aneuploidy was found in blood samples obtained during
      different phases of the menstrual cycle. In the case group, the mean value of
      aneuploid cells in the follicular and luteal phase samples was 10.0 and 6.3 %
      respectively and in the control group, it was 2.8 and 1.0 % (P < 0.0001). The
      difference in the case group varied between 0 and 8 % (3.6 +/- 2.1 %) and in the
      control group between 0 and 4 % (1.7 +/- 1.1 %). The specificity for detecting
      true X mosaicism was 0.875. We estimate that the initial diagnosis of X mosaicism
      could be correct in 68 % of patients with recurrent pregnancy loss. CONCLUSIONS:
      This observational study establishes that the time of blood sampling in relation
      to the menstrual cycle can influence lymphocyte X chromosome mosaicism. The
      results, further proven by additional controlled studies, would have practical
      implications for genetic counselling and fertility treatment.

PMID- 25399064
TI  - Evaluation of the impact of vitrification on the actin cytoskeleton of in vitro
      matured ovine oocytes by means of Raman microspectroscopy.
AB  - PURPOSE: Investigation of the changes induced by vitrification on the cortical F
      actin of in vitro matured ovine oocytes by Raman microspectroscopy (RMS).
      METHODS: Cumulus-oocyte complexes, recovered from the ovaries of slaughtered
      sheep, were matured in vitro and vitrified following the Minimum Essential Volume
      method using cryotops. The cortical region of metaphase II (MII) oocytes (1)
      exposed to vitrification solutions but not cryopreserved (CPA-exp), (2)
      vitrified/warmed (VITRI), and (3) untreated (CTR) was analyzed by RMS. A chemical
      map of one quadrant of single CPA-exp, VITRI and CTR oocytes was, also,
      performed. In order to identify the region of Raman spectra representative of the
      cortical F-actin modification, a group of in vitro matured oocytes were incubated
      with latrunculin-A (LATA), a specific F-actin destabilizing drug, and processed
      for RMS analysis. Thereafter, all the oocytes were stained with rhodamine
      phalloidin and evaluated by fluorescence confocal microscopy. Raman spectra of
      the oocytes were, statistically, analyzed using Principal Component Analysis
      (PCA). RESULTS: The PCA score plots showed a marked discrimination between CTR
      oocytes and CPA-exp/ VITRI groups. The main differences, highlighted by PCA
      loadings, were referable to proteins (1657, 1440 and 1300 cm(-1)) and, as
      indicated by LATA experiments, also included the changes of the F-actin. Analysis
      by confocal microscopy revealed a clear alteration of the cortical F-actin of CPA
      exp and VITRI oocytes confirming RMS results. CONCLUSIONS: Raman
      microspectroscopy may represent an alternative analytical tool for investigating
      the biochemical modification of the oocyte cortex, including the F-actin
      cytoskeleton, during vitrification of in vitro matured ovine oocytes.

PMID- 25399065
TI  - Effect of induced peritoneal endometriosis on oocyte and embryo quality in a
      mouse model.
AB  - PURPOSE: To assess the impact of peritoneal endometriosis on oocyte and embryo
      quality in a mouse model. METHODS: Peritoneal endometriosis was surgically
      induced in 33 B6CBA/F1 female mice (endometriosis group, N = 17) and sham
      operated were used as control (sham group, N = 16). Mice were superovulated 4
      weeks after surgery and mated or not, to collect E0.5-embryos or MII-oocytes.
      Evaluation of oocyte and zygote quality was done by immunofluorescence under
      spinning disk confocal microscopy. RESULTS: Endometriosis-like lesions were
      observed in all mice of endometriosis group. In both groups, a similar mean
      number of MII oocytes per mouse was observed in non-mated mice (30.2 vs 32.6),
      with a lower proportion of normal oocytes in the endometriosis group (61 vs 83 %,
      p < 0.0001). Abnormalities were incomplete extrusion or division of the first
      polar body and spindle abnormalities. The mean number of zygotes per mouse was
      lower in the endometriosis group (21 vs 35.5, p = 0.02) without difference in
      embryo quality. CONCLUSIONS: Our results support that induced peritoneal
      endometriosis in a mouse model is associated with a decrease in oocyte quality
      and embryo number. This experimental model allows further studies to understand
      mechanisms of endometriosis-associated infertility.

PMID- 25399066
TI  - Nanohybrid based on antibiotic encapsulated layered double hydroxide as a drug
      delivery system.
AB  - Nanohybrid of cefuroxime (CFO) with layered double hydroxide (LDH) has been
      prepared, and the rate of dissolution and bioavailability of CFO using nanohybrid
      as a drug delivery system has been broadly studied. The intercalation process was
      confirmed by X-ray diffraction, Fourier transform infrared spectroscopy, and
      thermogravimetric analysis. The CFO contents were found to be 19.0 wt% in the
      nanohybrid. The release mechanism of CFO was investigated with respect to anion
      and pH of the dissolution media such as gastric, intestinal and blood simulated
      media. The effect of pH was evaluated on the release of CFO from nanohybrid, and
      the dissolution of CFO from the nanohybrid was found to be a slow process at pH
      4.0, 6.8, and 7.4. Further the addition of Cl ion and PAM in release media did
      not affect the release rate of drug at pH 4.0 and 6.8, while at pH 7.4, Cl ion
      and PAM have significant role on the drug release. At pH 1.2, the release study
      shows that LDH dissolved in the acidic medium and CFO released in its molecular
      form. The release behavior suggests two mechanisms that are responsible for the
      release of CFO from nanohybrid: weathering (dependent on the pH) and ion exchange
      (highly dependent on the anions). Surface reactions mediated by solid weathering
      ruled the release in gastric fluid, whereas anion exchange determined CFO release
      in lysosomal, intestinal, and blood medium. In order to evaluate the drug release
      mechanism, the released data were fitted by mathematical models describing
      various kinetic.

PMID- 25399067
TI  - Fungal platform for direct chiral phosphonic building blocks production. Closer
      look on conversion pathway.
AB  - The application of Rhodospirillum toruloides strain allowed resolving the
      chemically synthesized racemic mixtures of following chiral aminophosphonic
      acids: 1-aminoethylphosphonic acid (1), 1-amino-1-iso-propyl-1-phosphonic acid
      (2), 1-amino-1-phenylmethylphosphonic acid (4) and 1-amino-2
      phenylethylphosphonic acid (3). The applied protocols resulted in obtaining pure
      (R)-1-aminoethylphosphonic acid (100 % of e.e.) and enantiomerically enriched
      mixtures of other phosphonates (73 % e.e. of (S)-1-amino-1-phenylmethylphosphonic
      acid, 51 % e.e. of (R)-1-amino-2-phenylethylphosphonic acid and 40 % e.e. of (S)
      1-amino-2-methylpropylphosphonic acid). Products are valuable chiral building
      blocks and serve as aminophosphonic acids platform for further applications.
      Performed experiments allowed to define the path of xenobiotics bioconversion.

PMID- 25399069
TI  - Optimizing ethanol and methane production from steam-pretreated, phosphoric acid
      impregnated corn stover.
AB  - Pretreatment is of vital importance in the production of ethanol and methane from
      agricultural residues. In this study, the effects of steam pretreatment with
      phosphoric acid on enzymatic hydrolysis (EH), simultaneous saccharification and
      fermentation (SSF), anaerobic digestion (AD) and the total energy output at three
      different temperatures were investigated. The effect of separating the solids for
      SSF and the liquid for AD was also studied and compared with using the whole
      slurry first in SSF and then in AD. Furthermore, the phosphoric acid was compared
      to previous studies using sulphuric acid or no catalyst. Using phosphoric acid
      resulted in higher yields than when no catalyst was used. However, compared with
      sulphuric acid, an improved yield was only seen with phosphoric acid in the case
      of EH. The higher pretreatment temperatures (200 and 210  degrees C) resulted in
      the highest yields after EH and SSF, while the highest methane yield was obtained
      with the lower pretreatment temperature (190  degrees C). The highest yield in
      terms of total energy recovery (78 %) was obtained after pretreatment at 190 
      degrees C, but a pretreatment temperature of 200  degrees C is, however, the best
      alternative since fewer steps are required (whole slurry in SSF and then in AD)
      and high product yields were obtained (76 %).

PMID- 25399068
TI  - Validation of a novel sequential cultivation method for the production of
      enzymatic cocktails from Trichoderma strains.
AB  - The development of new cost-effective bioprocesses for the production of
      cellulolytic enzymes is needed in order to ensure that the conversion of biomass
      becomes economically viable. The aim of this study was to determine whether a
      novel sequential solid-state and submerged fermentation method (SF) could be
      validated for different strains of the Trichoderma genus. Cultivation of the
      Trichoderma reesei Rut-C30 reference strain under SF using sugarcane bagasse as
      substrate was shown to be favorable for endoglucanase (EGase) production,
      resulting in up to 4.2-fold improvement compared with conventional submerged
      fermentation. Characterization of the enzymes in terms of the optimum pH and
      temperature for EGase activity and comparison of the hydrolysis profiles obtained
      using a synthetic substrate did not reveal any qualitative differences among the
      different cultivation conditions investigated. However, the thermostability of
      the EGase was influenced by the type of carbon source and cultivation system. All
      three strains of Trichoderma tested (T. reesei Rut-C30, Trichoderma harzianum,
      and Trichoderma sp INPA 666) achieved higher enzymatic productivity when
      cultivated under SF, hence validating the proposed SF method for use with
      different Trichoderma strains. The results suggest that this bioprocess
      configuration is a very promising development for the cellulosic biofuels
      industry. 

PMID- 25399070
TI  - Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice.
AB  - Mice homozygous for the gray tremor (gt) mutation have a pleiotropic phenotype
      that includes pigmentation defects, megacolon, whole body tremors, sporadic
      seizures, hypo- and dys-myelination of the central nervous system (CNS) and
      peripheral nervous system, vacuolation of the CNS, and early death. Vacuolation
      similar to that caused by prions was originally reported to be transmissible, but
      subsequent studies showed the inherited disease was not infectious. The gt
      mutation mapped to distal mouse chromosome 15, to the same region as Sox10, which
      encodes a transcription factor with essential roles in neural crest survival and
      differentiation. As dominant mutations in mouse or human SOX10 cause white
      spotting and intestinal aganglionosis, we screened the Sox10 coding region for
      mutations in gt/gt DNA. An adenosine to guanine transversion was identified in
      exon 2 that changes a highly conserved glutamic acid residue in the SOX10 DNA
      binding domain to glycine. This mutant allele was not seen in wildtype mice,
      including the related GT/Le strain, and failed to complement a Sox10 null allele.
      Gene expression analysis revealed significant down-regulation of genes involved
      in myelin lipid biosynthesis pathways in gt/gt brains. Knockout mice for some of
      these genes develop CNS vacuolation and/or myelination defects, suggesting that
      their down-regulation may contribute to these phenotypes in gt mutants and could
      underlie the neurological phenotypes associated with peripheral demyelinating
      neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome
      Hirschsprung disease, caused by mutations in human SOX10. 

PMID- 25399071
TI  - Genetic association between cyclin D1 polymorphism and breast cancer
      susceptibility.
AB  - Cyclin D1 polymorphism has been reported to be associated with risk of breast
      cancer, but the published studies have yielded controversial results. This study
      was undertaken to derive a precise risk estimate for the cyclin D1 polymorphism
      associated with breast cancer risk. We performed a search of EMBASE, PubMed, and
      Web of Science. In total, data from 18 publications were pooled and the
      association was assessed by odds ratios (ORs) with 95 % confidence intervals
      (CIs). This analysis showed that there was no obvious association between the
      cyclin D1 polymorphism and breast cancer risk in any of the analyzed genetic
      model. We found the same negative association in stratified analyses by
      ethnicity, source of controls, and sample size. Our meta-analysis provides an
      estimate that the presence of cyclin D1 polymorphism may not confer
      susceptibility to breast cancer. 

PMID- 25399072
TI  - Ageing and myeloid-derived suppressor cells: possible involvement in
      immunosenescence and age-related disease.
AB  - Infections, cancer and autoimmune diseases occur more frequently in the elderly,
      and although many factors contribute to this, the age-related remodelling of the
      immune system, termed immunosenescence, plays a major role. Over the last two
      decades, studies have evaluated the effect of ageing on both the adaptive and
      innate arms of the immune system and demonstrated compromised function in several
      cells including lymphocytes (naive, effector and memory), regulatory T and B
      cells, monocytes, neutrophils and NK cells. In addition, a well-documented
      feature of ageing is the increase in systemic inflammatory status
      (inflammageing), with raised serum levels of IL6, TNFalpha and CRP as well as
      reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of
      many reports as these cells show immunosuppressive properties and are present in
      higher frequency during infections, cancer and autoimmunity. Importantly, there
      have been publications showing increased numbers of myeloid-derived suppressor
      cells in aged mice and humans. In this review, we discuss the current literature
      on myeloid-derived suppressor cells, their possible role in altered immune
      function in the elderly, and whether it may be possible to manipulate these cells
      to alleviate age-related immune dysfunction. 

PMID- 25399073
TI  - Methylation of the nonhomologous end joining repair pathway genes does not
      explain the increase of translocations with aging.
AB  - Chromosome translocations are especially frequent in human lymphomas and
      leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so
      called tumor specific translocations have been detected in peripheral blood of
      healthy individuals, finding a higher frequency of some of them with aging. The
      inappropriate repair of DNA double strand breaks by the nonhomologous end joining
      (NHEJ) pathway is one of the reasons for a translocation to occur. Moreover,
      fidelity of this pathway has been shown to decline with age. Although the
      mechanism underlying this inefficacy is unknown, other repair pathways are
      inactivated by methylation with aging. In this study, we analyzed the implication
      of NHEJ genes methylation in the increase of translocations with the age. To this
      aim, we determined the relationship between translocations and aging in 565
      Spanish healthy individuals and correlated these data with the methylation status
      of 11 NHEJ genes. We found higher frequency of BCL2-JH and BCR-ABL (major)
      translocations with aging. In addition, we detected that two NHEJ genes (LIG4 and
      XRCC6) presented age-dependent promoter methylation changes. However, we did not
      observe a correlation between the increase of translocations and methylation,
      indicating that other molecular mechanisms are involved in the loss of NHEJ
      fidelity with aging. 

PMID- 25399075
TI  - Catching the eye with an abstract.

PMID- 25399074
TI  - T-2 and HT-2 toxins in oat flakes: development of a certified reference material.
AB  - Trichothecene mycotoxins, with T-2 and HT-2 toxins being the main representatives
      of the type A subgroup, are naturally and worldwide occurring contaminants
      frequently found in grain-based food and feed. Due to the high consumption of
      these products and the potential health risk associated herewith, concerns about
      the safety and quality of food and feed have increased over the last decades at
      both governmental and consumer levels. Since it is not possible to avoid their
      occurrence, tremendous efforts have been performed to identify and monitor
      mycotoxins in food and feed to make their consumption safe. However, suitable
      certified reference materials (CRMs) intended for quality assurance and quality
      control purposes are still lacking for many mycotoxin-matrix combinations.
      Therefore, in the framework of a European Reference Material (ERM(r)) project,
      the first CRM for T-2 and HT-2 toxin in ground oat flakes (ERM(r)-BC720) was
      developed according to the requirements of ISO Guide 35. The whole process of
      ERM(r)-BC720 development, including sample preparation, homogeneity and stability
      studies and value assignment, is presented. The assignment of the certified mass
      fractions was based upon an in-house study using high-performance liquid
      chromatography isotope-dilution tandem mass spectrometry. Simultaneously, an
      interlaboratory comparison study involving 24 expert laboratories was conducted
      in order to support the in-house certification study. The certified values and
      their corresponding expanded uncertainties (k = 2) for both T-2 and HT-2 toxin in
      ERM(r)-BC720, traceable to the international system of units, are (82 +/- 4) MUg
      kg(-1) and (81 +/- 4) MUg kg(-1), respectively. 

PMID- 25399076
TI  - Electrochemical DNA biosensor based on gold nanorods for detecting hepatitis B
      virus.
AB  - The purpose of this work was to fabricate an electrochemical DNA biosensor for
      detecting hepatitis B virus. Gold nanorods (GNRs), which are known for their
      conductivity, were used to increase surface area and consequently increase the
      immobilization of single-stranded DNA (ss-DNA) on the modified gold electrode.
      The GNRs were characterized via transmission electron microscopy. The morphology
      of the gold electrode before and after modification with GNRs was characterized
      by scanning electron microscopy. Atomic-force microscopy was used to evaluate the
      morphology of the GNR electrode surface before and after interaction with ss-DNA.
      Cyclic voltammetry was used to monitor DNA immobilization and hybridization,
      using [Co(phen)3](3+) as an electrochemical indicator. The target DNA sequences
      were quantified at a linear range from 1.0 * 10(-12) to 10.0 * 10(-6) mol L(-1),
      with a detection limit of 2.0 * 10(-12) mol L(-1) by 3sigma. The biosensor had
      good specificity for distinguishing complementary DNA in the presence of non
      complementary and mismatched DNA sequences. 

PMID- 25399077
TI  - Application of R-mode analysis to Raman maps: a different way of looking at
      vibrational hyperspectral data.
AB  - Hierarchical cluster analysis (HCA) is extensively used for the analysis of
      hyperspectral data. In this work, hyperspectral data sets obtained from Raman
      maps were analyzed using an alternative mode of cluster analysis, clustering
      "images" instead of spectra, under the assumption that images showing similar
      spatial distributions are related to the same chemical species. Such an approach
      was tested with two Raman maps: one simple "test map" of micro-crystals of four
      different compounds for a proof of principle and a map of a biological tissue
      (i.e., cartilage) as an example of chemically complex sample. In both cases, the
      "image-clustering" approach gave similar results as the traditional HCA, but at
      lower computational effort. The alternative approach proved to be particularly
      helpful in cases, as for the cartilage tissue, where concentration gradients of
      chemical composition are present. Moreover, with this approach, yielded
      information about correlation between bands in the average spectrum makes band
      assignment and spectral interpretation easier. 

PMID- 25399078
TI  - Down-regulation of testes-specific protease 50 induces apoptosis in human
      laryngocarcinoma HEp2 cells in a NF-kappaB-mediated pathway.
AB  - Testes-specific protease 50 is a newly reported threonine enzyme. It has similar
      amino acid sequences and enzymatic structures to some other serine proteases. It
      is proposed as a laryngocarcinoma-related gene in human beings. The physiological
      mechanism by which TSP50 exerts its promoting effects in laryngocarcinoma is not
      yet fully understood. The study investigated the function of TSP50 by suppressing
      its expression in the HEp2 cell line using a TSP50-specific short hairpin RNA
      (shRNA). Western bloting and real-time-PCR were used to detect the levels of
      TSP50. By using MTT, Wound healing, flow cytometric and tumorigenesis assays, the
      study tested the TSP50 role in human laryngocarcinoma cell growth and apoptosis.
      The results demonstrated that TSP50 knockdown could inhibit HEp2 cell
      proliferation and induce apoptosis in vitro in a NF-kappaB-mediated pathway. The
      tumorigenicity of TSP50 shRNA-expressing cells were decreased after inoculating
      into nude mice. The present results provide a new understanding of the TSP50 gene
      in the progression of laryngocarcinoma and put up a novel therapeutic target for
      treating this cancer. 

PMID- 25399079
TI  - Illegitimacy and sibship assignments in oil palm (Elaeis guineensis Jacq.) half
      sib families using single locus DNA microsatellite markers.
AB  - Oil palm breeding has been progressing very well in Southeast Asia, especially in
      Malaysia and Indonesia. Despite this progress, there are still problems due to
      the difficulty of controlled crossing in oil palm. Contaminated/illegitimate
      progeny has appeared in some breeding programs; late and failure of detection by
      the traditional method causes a waste of time and labor. The use of molecular
      markers improves the integrity of breeding programs in perennial crops such as
      oil palm. Four half-sib families with a total of 200 progeny were used in this
      study. Thirty polymorphic single locus DNA microsatellites markers were typed to
      identify the illegitimate individuals and to obtain the correct parental and
      progeny assignments by using the CERVUS and COLONY programs. Three illegitimate
      palms (1.5%) were found, and 16 loci proved to be sufficient for sibship
      assignments without parental genotypes by using the COLONY program. The pairwise
      likelihood score (PLS) method was better for half-sib family assignments than the
      full likelihood (FL) method.

PMID- 25399080
TI  - Molecular cloning of two molluscan caspases and gene functional analysis during
      Crassostrea angulata (Fujian oyster) larval metamorphosis.
AB  - Caspases have been demonstrated to possess important functions in apoptosis and
      immune system in vertebrate. But there is less information reported on the oyster
      larval development. In the present work, two full-length molluscan caspase genes,
      named Cacaspase-2 and Cacaspase-3, were characterized for the first time from
      Fujian oyster, Crassostrea angulata. Which respectively encode two predicted
      proteins both containing two caspase domains of p20 and p10 including the
      cysteine active site pentapeptide "QACRG" and the histidine active site
      signature. Otherwise Cacaspase-2 also contains a caspase recruitment domain.
      Homology and phylogenetic analysis showed that Cacaspase-2 shared high similarity
      with initiator caspase-2 groups, but Cacaspase-3 clustered together with
      executioner caspase-3 groups. Cacaspase-2 and Cacaspase-3 mRNA were both highly
      expressed in gills and labial palp and were significantly expressed highly in
      larvae during settlement and metamorphosis. Through the whole mount in situ
      hybridization, the location of Cacaspase-2 is in the foot of the oyster larvae
      and the location of Cacaspase-3 is in both the foot and velum tissues. These
      results implied that Cacaspase-2 and Cacaspase-3 genes play a key role in the
      loss of foot and Cacaspase-3 gene has an important function in the loss of velum
      during larvae metamorphosis in C. angulata. 

PMID- 25399082
TI  - Elevated PD-1 expression and decreased telomerase activity in memory T cells of
      patients with symptomatic Herpes Zoster infection.
AB  - We investigated PD-1 levels on VZV-specific CD8+ T-cells of patients with zoster
      and the effect of PD-1 on the telomerase activity. CD3, CD8, CD137 and PD-1
      expressions were analyzed on PBMCs from 9 symptomatic and 5 asymptomatic
      individuals. The effect of PD-1 blockade at the time of stimulation on the
      telomerase activity of non-senescent CD57-CD45RO+CD8+CD3+ memory T-cells was
      evaluated. PD-1 was elevated on CD8+ T-cells in patients. The frequency of PD-1+
      and CD137- cells in total CD3+CD8+ T cells of patients was elevated compared to
      controls. Telomerase activity of non-senescent memory T-cells was lower than that
      of controls. Blockade of PD-1 at the time of stimulation increased telomerase
      activity of non-senescent memory T-cells, accompanied by increased CD137
      expression. Low telomerase activity of the patients with reactivated zoster could
      be partially overcome by blocking PD-1 pathway.

PMID- 25399081
TI  - The effects of germacrone on lipopolysaccharide-induced acute lung injury in
      neonatal rats.
AB  - Germacrone is one of the main bioactive components in the traditional Chinese
      medicine Rhizoma curcuma and has been shown to possess an anti-inflammatory
      activity. Our present study aimed to investigate the protective effects of
      germacrone on lipopolysaccharide (LPS)-induced acute lung injury in neonatal
      rats. Results showed that germacrone treatment significantly decreased the
      expression of pro-inflammatory cytokines IL-6 and TNF-alpha. Meanwhile, the
      expression of anti-inflammatory mediators TGF-beta1 and IL-10 was obviously
      increased following germacrone administration. The LPS-induced pathological
      changes in neonatal rats were also attenuated by germacrone treatment. In vitro,
      MTT and EdU incorporation assay indicated that germacrone administration
      significantly increased the A549 cell viabilities in a dose-dependent manner.
      Besides, flow cytometry and TUNEL analysis showed that the cell apoptosis rate
      was significantly reduced in a concentration-dependent manner after germacrone
      injection. At the molecular level, we found that germacrone treatment promoted
      the expression of claudin-4 both in vivo and in vitro as shown by real time PCR
      and western blot. Collectively, our study demonstrated that germacrone protected
      neonatal rats against LPS-induced ALI partially by modulation of claudin-4.

PMID- 25399083
TI  - Docosahexaenoic acid (DHA) injection in spinal cord transection stimulates Na+,K+
      ATPase in skeletal muscle via beta 1 subunit.
AB  - Spinal cord injuries (SCI) induce a loss of skeletal muscle mass and functional
      capacity. The muscle excitability and contractility depend on the plasma membrane
      potential, regulated by transmembrane ion gradients, and thus necessarily on the
      Na+,K+-ATPase activity. The aim of this work was to evaluate the consequences of
      a spinal cord transection (SCT) on the skeletal muscle Na+,K+-ATPase and the
      impact of collateral GlyceroPhosphoLipids enriched in DocosaHexaenoic Acid (GPL
      DHA) administration. The Na+,K+-ATPase activity and membrane expression of Na+,K+
      ATPase alpha1, alpha2 and beta1 isoforms were assessed by K+-stimulated
      paranitrophenyl phosphatase (pNPPase) measurements and Western Blotting,
      respectively. The results show that spinal cord transection increased
      significantly (p<0.05) Na+,K+-ATPase activity in muscle by 25% and decreased the
      amounts of alpha1 isoform and alpha2 isoform expressions by 50% (p<0.05)
      respectively compared to controls. The results also show that early injection of
      GPL-DHA after SCT decreases in membrane skeletal muscle the alpha1 and alpha2
      isoforms expression but increases the membrane Na+,K+-ATPase activity. This
      treament partially restores the membrane expression of the beta1 subunit of the
      Na+,K+-ATPase. These data suggest that the increase of beta1 subunit expression
      is probably the main trigger to the membrane Na+,K+-ATPase activation following a
      trans-synaptic denervation.

PMID- 25399084
TI  - Overview and challenges of molecular technologies in the veterinary microbiology
      laboratory.
AB  - Terrestrial, aquatic, and aerial animals, either domestic or wild, humans, and
      plants all face similar health threats caused by infectious agents. Multifaceted
      anthropic pressure caused by an increasingly growing and resource-demanding human
      population has affected biodiversity at all scales, from the DNA molecule to the
      pathogen, to the ecosystem level, leading to species declines and extinctions
      and, also, to host-pathogen coevolution processes. Technological developments
      over the last century have also led to quantic jumps in laboratorial testing that
      have highly impacted animal health and welfare, ameliorated animal management and
      animal trade, safeguarded public health, and ultimately helped to "secure"
      biodiversity. In particular, the field of molecular diagnostics experienced
      tremendous technical progresses over the last two decades that significantly have
      contributed to our ability to study microbial pathogens in the clinical and
      research laboratories. This chapter highlights the strengths, weaknesses,
      opportunities, and threats (or challenges) of molecular technologies in the
      framework of a veterinary microbiology laboratory, in view of the latest
      advances.

PMID- 25399085
TI  - Significance and integration of molecular diagnostics in the framework of
      veterinary practice.
AB  - The field of molecular diagnostics in veterinary practice is rapidly evolving. An
      array of molecular techniques of different complexity is available to facilitate
      the fast and specific diagnosis of animal diseases. The choice for the adequate
      technique is dependent on the mission and attributions of the laboratory and
      requires both a knowledge of the molecular biology basis and of its limitations.
      The ability to quickly detect pathogens and their characteristics would allow for
      precise decision-making and target measures such as prophylaxis, appropriate
      therapy, and biosafety plans to control disease outbreaks. In practice, taking
      benefit of the huge amount of data that can be obtained using molecular
      techniques highlights the need of collaboration between veterinarians in the
      laboratory and practitioners.

PMID- 25399086
TI  - Biosafety principles and practices for the veterinary diagnostic laboratory.
AB  - Good biosafety and biocontainment programs and practices are critical components
      of the successful operation of any veterinary diagnostic laboratory. In this
      chapter we provide information and guidance on critical biosafety management
      program elements, facility requirements, protective equipment, and procedures
      necessary to ensure that the laboratory worker and the environment are adequately
      protected in the challenging work environment of the veterinary diagnostic
      laboratory in general and provide specific guidance for those laboratories
      employing molecular diagnostic techniques. 

PMID- 25399087
TI  - Veterinary biobank facility: development and management for diagnostic and
      research purposes.
AB  - Biobanking is an essential tool for ensuring easy availability of high-quality
      biomaterial collections that combine essential samples and epidemiological,
      clinical, and research data for the scientific community. Specimen collection is
      an integral part of clinical research. Indeed, every year throughout the world,
      millions of biological samples are stored for diagnostics and research, but in
      many fields the lack of biological material and models is a major hindrance for
      ongoing research. A biobank facility provides suitable samples for large-scale
      screening studies and database repositories. Software dedicated to biological
      banks simplify sample registration and identification, the cataloging of sample
      properties (type of sample/specimen, associated diseases and/or therapeutic
      protocols, environmental information, etc.), sample tracking, quality assurance,
      and specimen availability characterized by well-defined features. Biobank
      facilities must adopt good laboratory practices (GLPs) and a stringent quality
      control system and also comply with ethical issues, when required. The creation
      of a veterinary network can be useful under different aspects: the first one is
      related to the importance of animal sciences itself to improve research and
      strategies in the different branches of the veterinary area, and the second
      aspect is related to the possibility of data management harmonization to improve
      scientific cooperation.

PMID- 25399088
TI  - Biological specimen collection and processing for molecular analysis.
AB  - This chapter provides a standardized best practice approach to sample collection
      and handling for the purpose of nucleic acid (NA) extraction and PCR. These
      methods are described through text and clearly illustrated figures. Furthermore,
      for those cases in which transportation of samples cannot be accomplished due to
      the inability to maintain the cold chain or limitations on the import of live
      disease agents in diagnostic samples, the chapter describes the use of FTA cards
      for collection transport and NA preparation of samples for PCR. This chapter also
      makes emphasis in the best safety practices for handling of samples/tissues to
      avoid unnecessary disease exposures to laboratory personnel. Finally, NA
      extraction best practices and methods will be briefly outlined. 

PMID- 25399089
TI  - Validation of molecular diagnostic assays and quality assurance and control in
      the veterinary laboratory.
AB  - This chapter describes the process of validating in-house molecular assays
      although the principles described are equally relevant to all diagnostic assays.
      The best practice principles described below are based on the In Vitro Diagnostic
      Medical Devices Directive (IVDD) and associated documentation. Although
      compliance with these regulations is not required for diagnostic reagents used on
      animals, the principles are equally relevant to validation of all diagnostic
      assays, whatever their purpose. 

PMID- 25399090
TI  - Molecular approaches to recognize relevant and emerging infectious diseases in
      animals.
AB  - Since the introduction of the first molecular tests, there has been a continuous
      effort to develop new and improved assays for rapid and efficient detection of
      infectious agents. This has been motivated by a need for improved sensitivity as
      well as results that can be easily communicated. The experiences and knowledge
      gained at the World Organisation for Animal Health (OIE) Collaborating Centre for
      Biotechnology-based Diagnosis of Infectious Diseases in Veterinary Medicine,
      Uppsala, Sweden, will here be used to provide an overview of the different
      molecular approaches that can be used to diagnose and identify relevant and
      emerging infectious diseases in animals. 

PMID- 25399091
TI  - Real-time reverse transcriptase PCR for the detection of bluetongue virus.
AB  - In recent years, real-time reverse transcription polymerase chain reaction (rRT
      PCR) has become one of the most widely used methods for the diagnosis of
      infectious pathogens. The combined properties of high sensitivity, specificity,
      and speed, along with a low contamination risk, have made real-time PCR
      technology a highly attractive alternative to more conventional diagnostic
      methods. Numerous robust rRT-PCR systems have been developed and validated for
      important epizootic diseases of livestock, and in this chapter we describe an rRT
      PCR protocol for the detection of bluetongue virus. The assay uses
      oligonucleotide primers to specifically amplify target regions of the viral
      genome and a dual-labeled fluorogenic (TaqMan(r)) probe which allows for the
      assay to be performed in a closed-tube format, thus minimizing the potential for
      cross-contamination.

PMID- 25399092
TI  - Nested and multiplex real-time PCR using dual-labeled probes: detecting and
      discriminating Mycobacterium tuberculosis complex members in cultures and animal
      tissues.
AB  - Members of the Mycobacterium tuberculosis complex (MTC) are causative agents of
      tuberculosis (TB) in both humans and animals. In the last two decades, the
      accumulating knowledge of the nucleotide sequences of several genes, and of the
      whole genomes, of MTC members has allowed the development of novel molecular
      assays able to detect and discriminate between these species. However, despite
      the significant advances in the development of molecular assays for detecting MTC
      members in human samples, only a few assays have been described for detecting
      these agents in animal tissues. In this chapter we describe the use of two TaqMan
      ((r))-based real-time PCR approaches, highly sensitive and specific and easy to
      perform, to detect and identify veterinary-relevant MTC species in both animal
      tissue samples and cultures. 

PMID- 25399093
TI  - A real-time PCR assay for the diagnosis of gastrointestinal nematode infections
      of small ruminants.
AB  - The diagnosis of gastrointestinal nematode infections in small ruminants is
      central to studying the biology and epidemiology of these parasites and underpins
      their control. Traditional methods of diagnosis are inaccurate, time-consuming
      and laborious. Here, we describe a step-by-step protocol for the molecular-based
      diagnosis of infections by real-time PCR. 

PMID- 25399094
TI  - Improved detection of Mycobacterium bovis in bovine tissues using immunomagnetic
      separation approaches.
AB  - Immunomagnetic separation (IMS) represents a simple but effective method of
      selectively capturing and concentrating Mycobacterium bovis, the causative agent
      of bovine tuberculosis (bTB), from tissue samples. It is a physical cell
      separation technique that does not impact cell viability, unlike traditional
      chemical decontamination prior to culture. IMS is performed with paramagnetic
      beads coated with M. bovis-specific antibody and peptide binders. Once captured
      by IMS, M. bovis cells can be detected by either PCR or cultural detection
      methods. Increased detection rates of M. bovis, particularly from non-visibly
      lesioned lymph node tissues from bTB reactor animals, have recently been reported
      when IMS-based methods were employed. 

PMID- 25399095
TI  - Detection of fish pathogens by loop-mediated isothermal amplification (LAMP)
      technique.
AB  - Rapid detection of fish pathogens is mandatory for applying the crucial
      preventive and control measures to reduce fish losses and, consequently, minimize
      the economic impact of diseases on the fish farm owners. The currently used
      molecular diagnostic tools of fish infectious agents, such as PCR and RT-PCR, are
      sensitive and specific but still have some drawbacks. These tools are usually
      time consuming and laborious, need skilled persons, and require sophisticated
      devices to be performed. Therefore, next-generation tools for rapid diagnosis of
      fish infectious diseases were developed to conquer these shortages. One of these
      novel tools is the loop-mediated isothermal amplification (LAMP) technique. LAMP
      is considered a more advantageous tool than PCR because it needs only a heating
      block or a thermostatically controlled water bath as a source of constant
      temperature. It is considered to be more specific than the PCR assay as it uses 4
      6 primers, which may diminish the occurrence of false-positive results. The time
      required for the amplification process by LAMP is ranging from 30 min to 1 h
      comparing to 3-5 h in the case of PCR. The visual detection methods coupled with
      the LAMP assay eliminates the post-run processing for detection of the
      amplification products. Its sensitivity is either comparable with the PCR or
      better than it. A variety of LAMP assays were developed for simple and rapid
      detection of a diversity of fish pathogens. Herein, we describe how to perform a
      LAMP assay and troubleshoot any potential problem arising during the process. 

PMID- 25399096
TI  - Direct detection of Theileria annulata in bovine blood samples using standard and
      isothermal DNA amplification approaches.
AB  - Tropical theileriosis is a tick-borne disease responsible for important health
      problems in cattle, caused by the hemoprotozoan Theileria annulata.
      Traditionally, detection of Theileria pathogens in infected animals requires the
      microscopic examination of stained-blood smears and serological methods.
      Molecular diagnostic assays have been developed for the detection of Theileria
      parasites, including PCR-based and reverse line blotting approaches, but these
      methods usually demand qualified personnel, complex instrumentation, and
      expensive materials. Loop-mediated isothermal amplification (LAMP) can facilitate
      the design of molecular assays independent of the use of sophisticated equipment.
      In this chapter we describe the application of two molecular assays for the
      direct detection of T. annulata in bovine blood samples, based in real-time PCR
      and LAMP, both targeting the Tams1-encoding gene of this parasite. 

PMID- 25399097
TI  - Reverse line blot hybridization with species-specific oligonucleotide probes:
      application to piroplasm detection.
AB  - Reverse line blot (RLB) hybridization has become a well-established and widely
      used method for the multiplex identification of several Babesia and Theileria
      species in hosts and tick vectors. The procedure is based on the simultaneous PCR
      amplification of a polymorphic region of the 18S rRNA gene from different
      piroplasms followed by identification of the individual species by hybridization
      to species-specific oligonucleotide probes covalently linked to a nylon membrane
      in a macroarray format. 

PMID- 25399098
TI  - DNA microarray-based detection of multiple pathogens: Mycoplasma spp. and
      Chlamydia spp.
AB  - Rapid detection of slow-growing or non-culturable microorganisms, such as
      Mycoplasma spp. and Chlamydia spp., is still a challenge to diagnosticians in the
      veterinary field. In addition, as epidemiological evidence on the frequency of
      mixed infections involving two and more bacterial species has been emerging,
      detection methods allowing simultaneous identification of different pathogens are
      required. In the present chapter, we describe DNA microarray-based procedures for
      the detection of 83 Mollicutes species (Mycoplasma assay) and 11 Chlamydia spp.
      (Chlamydia assay). The assays are suitable for use in a routine diagnostic
      environment, as well as in microbiological research. 

PMID- 25399099
TI  - In situ hybridization with labeled probes: assessment of african Swine Fever
      virus in formalin-fixed paraffin-embedded tissues.
AB  - In situ hybridization (ISH) has become a very valuable molecular diagnostic tool
      to detect specific DNA or RNA sequences in biological samples through the use of
      complementary DNA- or RNA-labeled probes. Here, we describe an optimized in situ
      hybridization protocol to detect African swine fever virus (ASFV) DNA in formalin
      fixed, paraffin-embedded tissues using digoxigenin-labeled probes. 

PMID- 25399100
TI  - Fluorescence in situ hybridization for the tissue detection of bacterial
      pathogens associated with porcine infections.
AB  - Fluorescence in situ hybridization (FISH) is an efficient technique for the
      identification of specific bacteria in tissue of both experimental and
      spontaneous infections. The method detects specific sequences of nucleic acids by
      hybridization of fluorescently labeled probes to complementary target sequences
      within intact cells. FISH allows direct histological localization of the bacteria
      in the tissue and thereby a correlation between the infection and the
      histopathological changes present. This chapter presents protocols for FISH
      identification of bacterial pathogens in fixed deparaffinized tissue samples
      mounted on glass slides. Two different methods are presented: one is illustrated
      with the use of peptide nucleic acid (PNA) that is carried out directly on glass
      slides (Method I), whereas the other is exemplified by using a DNA probe in a
      Shandon rack (Method II). In the two methods, both PNA and DNA probes can be
      used. 

PMID- 25399101
TI  - Identification of animal Pasteurellaceae by MALDI-TOF mass spectrometry.
AB  - Species of the family Pasteurellaceae play an important role as primary or
      opportunistic, predominantly respiratory, pathogens in domestic and wild animals.
      Some of them cause severe disease with high economic losses in commercial animal
      husbandry. Hence, rapid and accurate differentiation of Pasteurellaceae is
      important and signifies a particular challenge to diagnostic laboratories.
      Identification and differentiation of Pasteurellaceae is mostly done using
      phenotypic tests or genetic identification based on sequence similarity of
      housekeeping genes, such as the rrs gene encoding the 16S ribosomal RNA (16S
      rRNA). Both approaches are time consuming, laborious, and costly, therefore often
      delaying the final diagnosis of disease or epidemics. Matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry represents an
      alternative rapid and reliable method for the differentiation of most members of
      the family Pasteurellaceae. It is able to differentiate within a few minutes the
      currently known 18 genera and most of the over 60 species and subspecies of
      Pasteurellaceae including many members encountered in veterinary diagnostic
      laboratories. A few closely related species and subspecies that cannot be
      discriminated by MALDI-TOF are easily identified further by complementary simple
      tests, such as hemolysis done simultaneously or routinely during pathogen
      isolation. 

PMID- 25399102
TI  - Gold nanoparticles as a potential tool for diagnosis of fish diseases.
AB  - Infectious diseases are a serious problem and a major contributor to severe
      economic losses in intensive fish culture. Therefore, rapid and sensitive
      detection of fish pathogens is extremely important. Although various assays for
      determination of fish pathogens have been developed, most of these diagnostic
      methods are time-consuming and laborious. To overcome these limitations,
      functional nanomaterials have been actively investigated to improve detection
      ability and rapidity of diagnostic assays. Gold nanoparticles (AuNPs) have been
      widely studied for their unique optical properties arising from their surface
      plasmon resonance, which is responsible for their large absorption and scattering
      properties. These unique properties are four to five orders of magnitude larger
      than those of conventional dyes and can be controlled by varying their sizes,
      shapes, and compositions. Moreover, AuNPs can be easily synthesized and
      functionalized with different biomolecules, including pathogen-specific
      oligonucleotides or antibodies. Recently, nanoparticle-based assays have been
      introduced as a tool for laboratory diagnosis. They have been used for the direct
      detection of unamplified nucleic acids in hybridization assays. Single- and
      double-stranded oligonucleotides can be adsorbed on AuNPs in colloidal solution
      under certain conditions. The result of the hybridization process can be visually
      detected within 1 min after addition of AuNPs, when the color of the reaction
      mixture changes from red to blue (positive reaction) or remains red (negative).
      The development of such nanoparticle-based strategies holds the potential to
      become powerful approaches for diagnosis of fish pathogens. 

PMID- 25399103
TI  - Nucleic-acid testing, new platforms and nanotechnology for point-of-decision
      diagnosis of animal pathogens.
AB  - Accurate disease diagnosis in animals is crucial for animal well-being but also
      for preventing zoonosis transmission to humans. In particular, livestock diseases
      may constitute severe threats to humans due to the particularly high physical
      contact and exposure and, also, be the cause of important economic losses, even
      in non-endemic countries, where they often arise in the form of rapid and
      devastating epidemics. Rapid diagnostic tests have been used for a long time in
      field situations, particularly during outbreaks. However, they mostly rely on
      serological approaches, which may confirm the exposure to a particular pathogen
      but may be inappropriate for point-of-decision (point-of-care) settings when
      emergency responses supported on early and accurate diagnosis are required.
      Moreover, they often exhibit modest sensitivity and hence significantly depend on
      later result confirmation in central or reference laboratories. The impressive
      advances observed in recent years in materials sciences and in nanotechnology, as
      well as in nucleic-acid synthesis and engineering, have led to an outburst of new
      in-the-bench and prototype tests for nucleic-acid testing towards point-of-care
      diagnosis of genetic and infectious diseases. Manufacturing, commercial,
      regulatory, and technical nature issues for field applicability more likely have
      hindered their wider entrance into veterinary medicine and practice than have
      fundamental science gaps. This chapter begins by outlining the current situation,
      requirements, difficulties, and perspectives of point-of-care tests for
      diagnosing diseases of veterinary interest. Nucleic-acid testing, particularly
      for the point of care, is addressed subsequently. A range of valuable signal
      transduction mechanisms commonly employed in proof-of-concept schemes and
      techniques born on the analytical chemistry laboratories are also described. As
      the essential core of this chapter, sections dedicated to the principles and
      applications of microfluidics, lab-on-a-chip, and nanotechnology for the
      development of point-of-care tests are presented. Microdevices already applied or
      under development for application in field diagnosis of animal diseases are
      reviewed.

PMID- 25399104
TI  - Molecular typing tools: from pattern recognition to genome-based algorithms.
AB  - In the present chapter, we discuss DNA-based typing methods for microbial
      pathogens that were frequently used in the past two decades and their essential
      features, as well as virtues and downsides. We conclude with an outlook on the
      fundamental changes that can be expected in the era of high-throughput genomics. 

PMID- 25399105
TI  - Characterization of Campylobacter jejuni and Campylobacter coli genotypes in
      poultry flocks by restriction fragment length polymorphism (RFLP) analysis.
AB  - We describe a simple, rapid, and discriminatory methodology that allows the
      routine molecular characterization of Campylobacter jejuni and Campylobacter coli
      isolates. The proposed approach is built on one of the earliest and simplest
      molecular typing methods ever, consisting on the analysis of the fragments of
      different lengths generated by digestion of homologous DNA sequences with
      specific restriction endonucleases, a process known as restriction fragment
      length polymorphism (RFLP) analysis. The strategy underneath the workflow
      reported here is meant to explore the polymorphisms of Campylobacter spp. flaA
      gene (flaA-RFLP) that allows the local investigation of the genetic diversity and
      distribution of C. coli and C. jejuni isolates from different sources, namely,
      chickens' caeca. Although not appropriate for global and long-term
      epidemiological studies as a single approach, flaA-RFLP analysis can be very
      useful in surveys limited in space and time and, for specific epidemiological
      settings, an alternative to more modern and resource-demanding techniques. 

PMID- 25399106
TI  - Pulsed-field gel electrophoresis (PFGE): application in population structure
      studies of bovine mastitis-causing streptococci.
AB  - Pulsed-field gel electrophoresis (PFGE) separates large DNA molecules by the use
      of an alternating electrical field, such that greater size resolution can be
      obtained when compared to normal agarose gel electrophoresis. PFGE is often
      employed to track pathogens and is a valuable typing scheme to detect and
      differentiate strains. Particularly, the contour-clamped homogeneous electric
      field (CHEF) PFGE system is considered to be the gold standard for use in
      epidemiological studies of many bacterial pathogens. Here we describe a PFGE
      protocol that was applicable to the study of bovine streptococci, namely,
      Streptococcus agalactiae (group B Streptococcus, GBS), Streptococcus dysgalactiae
      subsp. dysgalactiae (group C Streptococcus, GCS), and Streptococcus uberis-which
      are relevant pathogens causing mastitis, a highly prevalent and costly disease in
      dairy industry due to antibiotherapy and loss in milk production. 

PMID- 25399107
TI  - Multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) using
      multiplex PCR and multicolor capillary electrophoresis: application to the
      genotyping of Brucella species.
AB  - The multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) is a
      genetic typing method based on the evaluation of the number of repeated sequences
      in multiple selected loci of microbial DNA. Although several MLVA typing panels
      have been proposed for brucellae, the 16-loci panel is recognized as the standard
      genotyping method, also used for the Brucella international online database. This
      chapter describes a high-throughput MLVA-16 protocol using multiplex PCRs and
      multicolor capillary electrophoresis. 

PMID- 25399108
TI  - Multilocus sequence typing (MLST): markers for the traceability of pathogenic
      Leptospira strains.
AB  - Leptospirosis is a major zoonosis with worldwide distribution. Conventional
      serological typing is arduous and time consuming. Genotyping is increasingly
      applied for the typing and identification of leptospires and contributes to
      genetic and virulence divergence and molecular epidemiological characteristics
      such as host versus leptospires population interactions and dynamics. Presently,
      multilocus sequence typing (MLST) is the most robust approach. In this chapter,
      we describe the practical steps of two major multilocus sequence typing methods
      for leptospires. The first method (denoted as the 6 L scheme) is based on
      genotyping by phylogeny using concatenated sequences derived from six loci,
      including genes that encode outer membrane proteins and rrs and can be used for
      typing pathogenic species and strains of intermediate species. The second method
      (referred to as the 7 L scheme) uses seven loci on housekeeping genes and allows
      the analysis of seven major Leptospira pathogenic species. The 7 L scheme is web
      based and includes the option to analyze sequence types (STs). 

PMID- 25399109
TI  - Single-nucleotide polymorphism discrimination using high-resolution melting
      analysis for the genotyping of Bacillus anthracis.
AB  - High-resolution melting (HRM) is a post-PCR technique that determines with high
      precision the melt profile of PCR products using a new generation of double
      stranded DNA-binding dyes and accurate fluorescence data acquisition over small
      temperature increments. The method can be used to interrogate small sets of
      single-nucleotide polymorphisms (SNPs). Here, we describe a simple and cost
      effective HRM-based method for the screening of 14 phylogenetically informative
      SNPs within the genome of Bacillus anthracis that subtype the species into 13
      major sublineages or subgroups. Fourteen monoplex and seven duplex SNP
      discrimination assays have been designed. We detail the parameters most important
      for the successful application of HRM for B. anthracis genotyping. 

PMID- 25399110
TI  - Clustered regularly interspaced short palindromic repeats (CRISPRs) analysis of
      members of the Mycobacterium tuberculosis complex.
AB  - Typical CRISPR (clustered, regularly interspaced, short palindromic repeat)
      regions are constituted by short direct repeats (DRs), interspersed with
      similarly sized non-repetitive spacers, derived from transmissible genetic
      elements, acquired when the cell is challenged with foreign DNA. The analysis of
      the structure, in number and nature, of CRISPR spacers is a valuable tool for
      molecular typing since these loci are polymorphic among strains, originating
      characteristic signatures. The existence of CRISPR structures in the genome of
      the members of Mycobacterium tuberculosis complex (MTBC) enabled the development
      of a genotyping method, based on the analysis of the presence or absence of 43
      oligonucleotide spacers separated by conserved DRs. This method, called
      spoligotyping, consists on PCR amplification of the DR chromosomal region and
      recognition after hybridization of the spacers that are present. The workflow
      beneath this methodology implies that the PCR products are brought onto a
      membrane containing synthetic oligonucleotides that have complementary sequences
      to the spacer sequences. Lack of hybridization of the PCR products to a specific
      oligonucleotide sequence indicates absence of the correspondent spacer sequence
      in the examined strain. Spoligotyping gained great notoriety as a robust
      identification and typing tool for members of MTBC, enabling multiple
      epidemiological studies on human and animal tuberculosis. 

PMID- 25399111
TI  - Rapid microarray-based genotyping of Chlamydia spp. strains from clinical tissue
      samples.
AB  - Pathogenic Chlamydia (C.) psittaci and C. trachomatis strains can be genotyped
      based on variations in the ompA genomic locus. In the present chapter, we
      describe rapid genotyping assays for both chlamydial agents using the
      ArrayStripTM (AS) microarray platform. The test is targeting multiple
      discriminatory sites in the variable domains of the ompA gene by using 35 (C.
      psittaci) and 61 (C. trachomatis) oligonucleotide probes representing genotype
      specific polymorphisms. In addition to discrimination among the established
      genotypes, this approach allows identification of atypical strains that were not
      accessible to typing using previously established techniques, such as PCR-RFLP or
      serotyping. The present DNA microarray assay can be conducted directly on
      clinical tissue samples and is suitable for tracing epidemiological chains and
      exploring the dissemination of particular genotypes. The procedure is easy to
      handle and economically affordable, and it allows genotyping of up to 32 clinical
      samples per day, thus lending itself for routine diagnosis as well.

PMID- 25399112
TI  - Multiplexed genotyping of Bacillus anthracis by Luminex xMap suspension array.
AB  - The Luminex(r) xTAG technology is a medium to high throughput, open methodology
      able to test many single nucleotide polymorphisms (SNPs) in a single reaction and
      a minimum time. Multiplex SNPs interrogation are conducted on the Luminex xMAP
      system, which uses lasers to read universal tag, color-coded microspheres that
      attach to specific nucleic acid sequences. The present method describes a
      Multiplex Oligonucleotide Ligation-PCR procedure (MOL-PCR) for the simultaneous
      interrogation of 13 phylogenetically informative SNPs within the genome of
      Bacillus anthracis. The reported 13-plex assay enables efficient B. anthracis
      genotyping into major sublineages and groups. While cost-effective compared to
      other monoplex methods, the present MOL-PCR method also offers a high degree of
      flexibility and scalability. It can easily accommodate newly identified SNPs to
      increase resolving power to the canSNP typing of B. anthracis.

PMID- 25399113
TI  - Next-generation sequencing in veterinary medicine: how can the massive amount of
      information arising from high-throughput technologies improve diagnosis, control,
      and management of infectious diseases?
AB  - The development of high-throughput molecular technologies and associated
      bioinformatics has dramatically changed the capacities of scientists to produce,
      handle, and analyze large amounts of genomic, transcriptomic, and proteomic data.
      A clear example of this step-change is represented by the amount of DNA sequence
      data that can be now produced using next-generation sequencing (NGS) platforms.
      Similarly, recent improvements in protein and peptide separation efficiencies and
      highly accurate mass spectrometry have promoted the identification and
      quantification of proteins in a given sample. These advancements in biotechnology
      have increasingly been applied to the study of animal infectious diseases and are
      beginning to revolutionize the way that biological and evolutionary processes can
      be studied at the molecular level. Studies have demonstrated the value of NGS
      technologies for molecular characterization, ranging from metagenomic
      characterization of unknown pathogens or microbial communities to molecular
      epidemiology and evolution of viral quasispecies. Moreover, high-throughput
      technologies now allow detailed studies of host-pathogen interactions at the
      level of their genomes (genomics), transcriptomes (transcriptomics), or proteomes
      (proteomics). Ultimately, the interaction between pathogen and host biological
      networks can be questioned by analytically integrating these levels (integrative
      OMICS and systems biology). The application of high-throughput biotechnology
      platforms in these fields and their typical low-cost per information content has
      revolutionized the resolution with which these processes can now be studied. The
      aim of this chapter is to provide a current and prospective view on the
      opportunities and challenges associated with the application of massive parallel
      sequencing technologies to veterinary medicine, with particular focus on
      applications that have a potential impact on disease control and management.

PMID- 25399114
TI  - Impact of next-generation technologies on exploring socioeconomically important
      parasites and developing new interventions.
AB  - High-throughput molecular and computer technologies have become instrumental for
      systems biological explorations of pathogens, including parasites. For instance,
      investigations of the transcriptomes of different developmental stages of
      parasitic nematodes give insights into gene expression, regulation and function
      in a parasite, which is a significant step to understanding their biology, as
      well as interactions with their host(s) and disease. This chapter (1) gives a
      background on some key parasitic nematodes of socioeconomic importance, (2)
      describes sequencing and bioinformatic technologies for large-scale studies of
      the transcriptomes and genomes of these parasites, (3) provides some recent
      examples of applications and (4) emphasizes the prospects of fundamental
      biological explorations of parasites using these technologies for the development
      of new interventions to combat parasitic diseases. 

PMID- 25399115
TI  - Functional genomics of tick vectors challenged with the cattle parasite Babesia
      bigemina.
AB  - Ticks are obligate hematophagous ectoparasites considered as vectors of animal
      diseases, having a huge economic impact in cattle industry. Babesia spp. are tick
      borne pathogens that cause a disease called babesiosis in a wide range of animals
      and in humans. Control of tick infestations is mainly based on the use of
      acaricides, which have limited efficacy reducing tick infestations, mostly due to
      wrong usage, and is often accompanied by the selection of acaricide-resistant
      ticks, environmental contamination, and contamination of milk and meat products.
      Vaccines affecting both vector and pathogens constitute new control strategies
      for tick and tick-borne diseases and are, therefore, a good alternative to
      chemical control. In this chapter we describe the identification of Rhipicephalus
      (Boophilus) annulatus genes differentially expressed in response to infection
      with B. bigemina by using suppression-subtractive hybridization (SSH), which
      allows the identification of differentially expressed genes. The results of the
      SSH studies are validated by real-time reverse transcription (RT)-PCR. Functional
      analyses are conducted by RNAi on selected R. annulatus genes to determine their
      putative role in B. bigemina-tick interactions. Gathered data may be useful for
      the future development of improved vaccines and vaccination strategies to control
      babesiosis.

PMID- 25399116
TI  - Metagenomic approaches to disclose disease-associated pathogens: detection of
      viral pathogens in honeybees.
AB  - Metagenomic approaches have become invaluable for culture-independent and
      sequence-independent detection and characterization of disease-associated
      pathogens. Here, the sequential steps from sampling to verification of results
      are described for a metagenomic-based approach to detect potential pathogens in
      honeybees. The pre-sequencing steps are given in detail, but due to the rapid
      development of sequencing technologies, all platform-specific procedures, as well
      as subsequent bioinformatics analysis, are more generally described. It should
      also be noted that this approach could, with minor modifications, be adapted for
      other organisms and sample matrices. 

PMID- 25399117
TI  - Proteomics characterization of tick-host-pathogen interactions.
AB  - Ticks are blood-feeding arthropod ectoparasites of wild and domestic animals that
      transmit disease-causing pathogens to humans and animals worldwide and a good
      model for the characterization of tick-host-pathogen interactions. Tick-host
      pathogen interactions consist of dynamic processes involving genetic traits of
      hosts, pathogens, and ticks that mediate their development and survival.
      Proteomics provides information on the protein content of cells and tissues that
      may differ from results at the transcriptomics level and may be relevant for
      basic biological studies and vaccine antigen discovery. In this chapter, we
      describe various methods for protein extraction and for proteomics analysis in
      ticks based on one-dimensional gel electrophoresis to characterize tick-host
      pathogen interactions. Particularly relevant for this characterization is the use
      of blood-fed ticks. Therefore, we put special emphasis on working with replete
      ticks collected after feeding on vertebrate hosts. 

PMID- 25399118
TI  - Detection of hotspots and rapid determination of methane emissions from landfills
      via a ground-surface method.
AB  - We present a method for the rapid determination of methane emissions from
      landfills based on atmospheric dispersion theory, which suggests that the methane
      concentration, at a small distance from the soil/atmosphere interface, is
      proportional to its flux. Thus, after suitable calibration, the determination of
      methane concentrations close to the ground allows for flux determination in a
      shorter time than with standard enclosure techniques. This concept was tested
      using a surface probe in direct contact with the ground. The probe extracts a
      continuous sample of the air at the probe/ground interface and transports it to a
      portable methane analyzer. It was observed that stable methane concentrations
      were measured 30 s after the probe was positioned at the measurement point. These
      concentrations correlated well with the fluxes measured by standard static
      chambers. The method was used to determine the fluxes at 217 points within a
      90,000 m(2) landfill. These measurements facilitated mapping of the CH4 emissions
      and the localization of hotspots. We conclude that the method is simple,
      effective, and relatively quick, compared to existing standard methods. 

PMID- 25399119
TI  - Evaluation of acidity estimation methods for mine drainage, Pennsylvania, USA.
AB  - Eighteen sites impacted by abandoned mine drainage (AMD) in Pennsylvania were
      sampled and measured for pH, acidity, alkalinity, metal ions, and sulfate. This
      study compared the accuracy of four acidity calculation methods with measured hot
      peroxide acidity and identified the most accurate calculation method for each
      site as a function of pH and sulfate concentration. Method E1 was the sum of
      proton and acidity based on total metal concentrations; method E2 added
      alkalinity; method E3 also accounted for aluminum speciation and temperature
      effects; and method E4 accounted for sulfate speciation. To evaluate errors
      between measured and predicted acidity, the Nash-Sutcliffe efficiency (NSE), the
      coefficient of determination (R (2)), and the root mean square error to standard
      deviation ratio (RSR) methods were applied. The error evaluation results show
      that E1, E2, E3, and E4 sites were most accurate at 0, 9, 4, and 5 of the sites,
      respectively. Sites where E2 was most accurate had pH greater than 4.0 and less
      than 400 mg/L of sulfate. Sites where E3 was most accurate had pH greater than
      4.0 and sulfate greater than 400 mg/L with two exceptions. Sites where E4 was
      most accurate had pH less than 4.0 and more than 400 mg/L sulfate with one
      exception. The results indicate that acidity in AMD-affected streams can be
      accurately predicted by using pH, alkalinity, sulfate, Fe(II), Mn(II), and
      Al(III) concentrations in one or more of the identified equations, and that the
      appropriate equation for prediction can be selected based on pH and sulfate
      concentration. 

PMID- 25399120
TI  - Fishers' knowledge as a source of information about the estuarine dolphin
      (Sotalia guianensis, van Beneden, 1864).
AB  - Fishers' local ecological knowledge (LEK) is an additional tool to obtain
      information about cetaceans, regarding their local particularities, fishing
      interactions, and behavior. However, this knowledge could vary in depth of detail
      according to the level of interaction that fishers have with a specific species.
      This study investigated differences in small-scale fishers' LEK regarding the
      estuarine dolphin (Sotalia guianensis) in three Brazilian northeast coastal
      communities where fishing is practiced in estuarine lagoons and/or coastal waters
      and where dolphin-watching tourism varies from incipient to important. The
      fishers (N = 116) were asked about general characteristics of S. guianensis and
      their interactions with this dolphin during fishing activities. Compared to
      lagoon fishers, coastal fishers showed greater knowledge about the species but
      had more negative interactions with the dolphin during fishing activities.
      Coastal fishing not only offered the opportunity for fishers to observe a wider
      variety of the dolphin's behavior, but also implied direct contact with the
      dolphins, as they are bycaught in coastal gillnets. Besides complementing
      information that could be used for the management of cetaceans, this study shows
      that the type of environment most used by fishers also affects the accuracy of
      the information they provide. When designing studies to gather information on
      species and/or populations with the support of fishers, special consideration
      should be given to local particularities such as gear and habitats used within
      the fishing community. 

PMID- 25399121
TI  - Evaluation of PAH contamination in soil treated with solid by-products from shale
      pyrolysis.
AB  - The aim of this work was to evaluate the concentrations of polycyclic aromatic
      hydrocarbons (PAHs) in soils to which solid shale materials (SSMs) were added as
      soil conditioners. The SSMs were derived from the Petrosix pyrolysis process
      developed by Petrobras (Brazil). An improved ultrasonic agitation method was used
      to extract the PAHs from the solid samples (soils amended with SSMs), and the
      concentrations of the compounds were determined by gas chromatography coupled to
      mass spectrometry (GC-MS). The procedure provided satisfactory recoveries,
      detection limits, and quantification limits. The two-, three-, and four-ring PAHs
      were most prevalent, and the highest concentration was obtained for phenanthrene
      (978 +/- 19 MUg kg(-1) in a pyrolyzed shale sample). The use of
      phenanthrene/anthracene and fluoranthene/pyrene ratios revealed that the PAHs
      were derived from petrogenic rather than pyrogenic sources. The measured PAH
      concentrations did not exceed national or international limit values, suggesting
      that the use of SSMs as soil conditioners should not cause environmental damage.

PMID- 25399122
TI  - Communication: On the consistency of approximate quantum dynamics simulation
      methods for vibrational spectra in the condensed phase.
AB  - Including quantum mechanical effects on the dynamics of nuclei in the condensed
      phase is challenging, because the complexity of exact methods grows exponentially
      with the number of quantum degrees of freedom. Efforts to circumvent these
      limitations can be traced down to two approaches: methods that treat a small
      subset of the degrees of freedom with rigorous quantum mechanics, considering the
      rest of the system as a static or classical environment, and methods that treat
      the whole system quantum mechanically, but using approximate dynamics. Here, we
      perform a systematic comparison between these two philosophies for the
      description of quantum effects in vibrational spectroscopy, taking the Embedded
      Local Monomer model and a mixed quantum-classical model as representatives of the
      first family of methods, and centroid molecular dynamics and thermostatted ring
      polymer molecular dynamics as examples of the latter. We use as benchmarks D2O
      doped with HOD and pure H2O at three distinct thermodynamic state points (ice Ih
      at 150 K, and the liquid at 300 K and 600 K), modeled with the simple q-TIP4P/F
      potential energy and dipole moment surfaces. With few exceptions the different
      techniques yield IR absorption frequencies that are consistent with one another
      within a few tens of cm(-1). Comparison with classical molecular dynamics
      demonstrates the importance of nuclear quantum effects up to the highest
      temperature, and a detailed discussion of the discrepancies between the various
      methods let us draw some (circumstantial) conclusions about the impact of the
      very different approximations that underlie them. Such cross validation between
      radically different approaches could indicate a way forward to further improve
      the state of the art in simulations of condensed-phase quantum dynamics. 

PMID- 25399123
TI  - Communication: HK propagator uniformized along a one-dimensional manifold in
      weakly anharmonic systems.
AB  - A simplification of the Heller-Herman-Kluk-Kay (HK) propagator is presented that
      does not suffer from the need for an increasing number of trajectories with
      dimensions of the system under study. This is accomplished by replacing HK's
      uniformizing integral over all of phase space by a one-dimensional curve that is
      appropriately selected to lie along the fastest growing manifold of a defining
      trajectory. It is shown that this modification leads to eigenspectra of quantum
      states in weakly anharmonic systems that can outperform the comparatively
      computationally cheap thawed Gaussian approximation method and frequently
      approach the accuracy of spectra obtained with the full HK propagator. 

PMID- 25399124
TI  - Communication: Finding destructive interference features in molecular transport
      junctions.
AB  - Associating molecular structure with quantum interference features in electrode
      molecule-electrode transport junctions has been difficult because existing
      guidelines for understanding interferences only apply to conjugated hydrocarbons.
      Herein we use linear algebra and the Landauer-Buttiker theory for electron
      transport to derive a general rule for predicting the existence and locations of
      interference features. Our analysis illustrates that interferences can be
      directly determined from the molecular Hamiltonian and the molecule-electrode
      couplings, and we demonstrate its utility with several examples. 

PMID- 25399125
TI  - Communication: Global minimum search of Ag10+ with molecular beam optical
      spectroscopy.
AB  - The present study is focused on the optical properties of the Ag10+ cluster in
      the photon energy range homega = 1.9-4.4 eV. Absorption spectra are recorded by
      longitudinal molecular beam depletion spectroscopy and compared to optical
      response calculations using time-dependent density functional theory. Several
      cluster isomers obtained by the new pool-based parallel implementation of the
      Birmingham Cluster Genetic Algorithm, coupled with density functional theory, are
      used in excited state calculations. The experimental observations, together with
      additional simulations of ion mobilities for the several geometries found within
      this work using different models, clearly identify the ground state isomer of
      Ag10+ to be composed of two orthogonal interpenetrating pentagonal bipyramids,
      having overall D(2d) symmetry.

PMID- 25399126
TI  - Semiclassical Monte Carlo: a first principles approach to non-adiabatic molecular
      dynamics.
AB  - Modeling the dynamics of photophysical and (photo)chemical reactions in extended
      molecular systems is a new frontier for quantum chemistry. Many dynamical
      phenomena, such as intersystem crossing, non-radiative relaxation, and charge and
      energy transfer, require a non-adiabatic description which incorporate
      transitions between electronic states. Additionally, these dynamics are often
      highly sensitive to quantum coherences and interference effects. Several methods
      exist to simulate non-adiabatic dynamics; however, they are typically either too
      expensive to be applied to large molecular systems (10's-100's of atoms), or they
      are based on ad hoc schemes which may include severe approximations due to
      inconsistencies in classical and quantum mechanics. We present, in detail, an
      algorithm based on Monte Carlo sampling of the semiclassical time-dependent
      wavefunction that involves running simple surface hopping dynamics, followed by a
      post-processing step which adds little cost. The method requires only a few
      quantities from quantum chemistry calculations, can systematically be improved,
      and provides excellent agreement with exact quantum mechanical results. Here we
      show excellent agreement with exact solutions for scattering results of standard
      test problems. Additionally, we find that convergence of the wavefunction is
      controlled by complex valued phase factors, the size of the non-adiabatic
      coupling region, and the choice of sampling function. These results help in
      determining the range of applicability of the method, and provide a starting
      point for further improvement. 

PMID- 25399127
TI  - Evaluation of the constant potential method in simulating electric double-layer
      capacitors.
AB  - A major challenge in the molecular simulation of electric double layer capacitors
      (EDLCs) is the choice of an appropriate model for the electrode. Typically, in
      such simulations the electrode surface is modeled using a uniform fixed charge on
      each of the electrode atoms, which ignores the electrode response to local charge
      fluctuations in the electrolyte solution. In this work, we evaluate and compare
      this Fixed Charge Method (FCM) with the more realistic Constant Potential Method
      (CPM), [S. K. Reed et al., J. Chem. Phys. 126, 084704 (2007)], in which the
      electrode charges fluctuate in order to maintain constant electric potential in
      each electrode. For this comparison, we utilize a simplified LiClO4
      acetonitrile/graphite EDLC. At low potential difference (DeltaPsi ? 2 V), the two
      methods yield essentially identical results for ion and solvent density profiles;
      however, significant differences appear at higher DeltaPsi. At DeltaPsi ? 4 V,
      the CPM ion density profiles show significant enhancement (over FCM) of "inner
      sphere adsorbed" Li(+) ions very close to the electrode surface. The ability of
      the CPM electrode to respond to local charge fluctuations in the electrolyte is
      seen to significantly lower the energy (and barrier) for the approach of Li(+)
      ions to the electrode surface. 

PMID- 25399128
TI  - Periodic boundary conditions for long-time nonequilibrium molecular dynamics
      simulations of incompressible flows.
AB  - This work presents a generalization of the Kraynik-Reinelt (KR) boundary
      conditions for nonequilibrium molecular dynamics simulations. In the simulation
      of steady, homogeneous flows with periodic boundary conditions, the simulation
      box deforms with the flow, and it is possible for image particles to become
      arbitrarily close, causing a breakdown in the simulation. The KR boundary
      conditions avoid this problem for planar elongational flow and general planar
      mixed flow [T. A. Hunt, S. Bernardi, and B. D. Todd, J. Chem. Phys. 133, 154116
      (2010)] through careful choice of the initial simulation box and by periodically
      remapping the simulation box in a way that conserves image locations. In this
      work, the ideas are extended to a large class of three-dimensional flows by using
      multiple remappings for the simulation box. The simulation box geometry is no
      longer time-periodic (which was shown to be impossible for uniaxial and biaxial
      stretching flows in the original work by Kraynik and Reinelt [Int. J. Multiphase
      Flow 18, 1045 (1992)]. The presented algorithm applies to all flows with
      nondefective flow matrices, and in particular, to uniaxial and biaxial flows. 

PMID- 25399129
TI  - Improving triplet-triplet-annihilation based upconversion systems by tuning their
      topological structure.
AB  - Materials capable to perform upconversion of light transform the photon spectrum
      and can be used to increase the efficiency of solar cells by upconverting sub
      bandgap photons, increasing the density of photons able to generate an electron
      hole pair in the cell. Incoherent solar radiation suffices to activate
      upconverters based on sensitized triplet-triplet annihilation, which makes them
      particularly suited for this task. This process requires two molecular species,
      sensitizers absorbing low energy photons, and emitters generating higher
      frequency photons. Successful implementations exist in solutions and solids.
      However, solid upconverters exhibit lower efficiency than those in solution,
      which poses a serious problem for real applications. In the present work, we
      suggest a new strategy to increase the efficiency of sensitized upconverters that
      exploits the solid nature of the material. We show that an upconversion model
      system with molecules distributed as clusters outperforms a system with a random
      distribution of molecules, as used in current upconverters. Our simulations
      reveal a high potential for improvement of upconverter systems by exploring
      different structural configurations of the molecules. The implementation of
      advanced structures can push the performance of solid upconverters further
      towards the theoretical limit and a step closer to technological application of
      low power upconversion. 

PMID- 25399130
TI  - Regularizing the molecular potential in electronic structure calculations. I. SCF
      methods.
AB  - We present a method to remove the singular nuclear potential in a molecule and
      replace it with a regularized potential that is more amenable to be represented
      numerically. The singular nuclear potential is canceled by the similarity
      transformed kinetic energy operator giving rise to an effective nuclear potential
      that contains derivative operators acting on the wave function. The method is
      fully equivalent to the non-similarity-transformed version. We give numerical
      examples within the framework of multi-resolution analysis for medium-sized
      molecules. 

PMID- 25399131
TI  - Regularizing the molecular potential in electronic structure calculations. II.
      Many-body methods.
AB  - In Paper I of this series [F. A. Bischoff, "Regularizing the molecular potential
      in electronic structure calculations. I. SCF methods," J. Chem. Phys. 141, 184105
      (2014)] a regularized molecular Hamilton operator for electronic structure
      calculations was derived and its properties in SCF calculations were studied. The
      regularization was achieved using a correlation factor that models the electron
      nuclear cusp. In the present study we extend the regularization to correlated
      methods, in particular the exact solution of the two-electron problem, as well as
      second-order many body perturbation theory. The nuclear and electronic
      correlation factors lead to computations with a smaller memory footprint because
      the singularities are removed from the working equations, which allows coarser
      grid resolution while maintaining the precision. Numerical examples are given. 

PMID- 25399132
TI  - The spin polarized linear response from density functional theory: theory and
      application to atoms.
AB  - Within the context of spin polarized conceptual density functional theory, the
      spin polarized linear response functions are introduced both in the [N, N(s)] and
      [N(alpha), N(beta)] representations. The mathematical relations between the spin
      polarized linear response functions in both representations are examined and an
      analytical expression for the spin polarized linear response functions in the
      [N(alpha), N(beta)] representation is derived. The spin polarized linear response
      functions were calculated for all atoms up to and including argon. To simplify
      the plotting of our results, we integrated chi(r, r') to a quantity chi(r, r'),
      circumventing the theta and phi dependence. This allows us to plot and to
      investigate the periodicity throughout the first three rows in the periodic table
      within the two different representations. For the first time, chi(alphabeta)(r,
      r'), chi(betaalpha)(r, r'), and chi(SS)(r, r') plots have been calculated and
      discussed. By integration of the spin polarized linear response functions,
      different components to the polarisability, alpha(alphaalpha), alpha(alphabeta),
      alpha(betaalpha), and alpha(betabeta) have been calculated.

PMID- 25399133
TI  - Quantum, classical, and hybrid QM/MM calculations in solution: general
      implementation of the ddCOSMO linear scaling strategy.
AB  - We present the general theory and implementation of the Conductor-like Screening
      Model according to the recently developed ddCOSMO paradigm. The various
      quantities needed to apply ddCOSMO at different levels of theory, including
      quantum mechanical descriptions, are discussed in detail, with a particular focus
      on how to compute the integrals needed to evaluate the ddCOSMO solvation energy
      and its derivatives. The overall computational cost of a ddCOSMO computation is
      then analyzed and decomposed in the various steps: the different relative weights
      of such contributions are then discussed for both ddCOSMO and the fastest
      available alternative discretization to the COSMO equations. Finally, the scaling
      of the cost of the various steps with respect to the size of the solute is
      analyzed and discussed, showing how ddCOSMO opens significantly new possibilities
      when cheap or hybrid molecular mechanics/quantum mechanics methods are used to
      describe the solute. 

PMID- 25399134
TI  - Quantum partition functions of composite particles in a hydrogen-helium plasma
      via path integral Monte Carlo.
AB  - We compute two- and three-body cluster functions that describe contributions of
      composite entities, like hydrogen atoms, ions H(-), H2(+), and helium atoms, and
      also charge-charge and atom-charge interactions, to the equation of state of a
      hydrogen-helium mixture at low density. A cluster function has the structure of a
      truncated virial coefficient and behaves, at low temperatures, like a usual
      partition function for the composite entity. Our path integral Monte Carlo
      calculations use importance sampling to sample efficiently the cluster partition
      functions even at low temperatures where bound state contributions dominate. We
      also employ a new and efficient adaptive discretization scheme that allows one
      not only to eliminate Coulomb divergencies in discretized path integrals, but
      also to direct the computational effort where particles are close and thus
      strongly interacting. The numerical results for the two-body function agree with
      the analytically known quantum second virial coefficient. The three-body cluster
      functions are compared at low temperatures with familiar partition functions for
      composite entities.

PMID- 25399135
TI  - Spatial resolution of the electrical conductance of ionic fluids using a Green
      Kubo method.
AB  - We present a Green-Kubo method to spatially resolve transport coefficients in
      compositionally heterogeneous mixtures. We develop the underlying theory based on
      well-known results from mixture theory, Irving-Kirkwood field estimation, and
      linear response theory. Then, using standard molecular dynamics techniques, we
      apply the methodology to representative systems. With a homogeneous salt water
      system, where the expectation of the distribution of conductivity is clear, we
      demonstrate the sensitivities of the method to system size, and other physical
      and algorithmic parameters. Then we present a simple model of an electrochemical
      double layer where we explore the resolution limit of the method. In this system,
      we observe significant anisotropy in the wall-normal vs. transverse ionic
      conductances, as well as near wall effects. Finally, we discuss extensions and
      applications to more realistic systems such as batteries where detailed
      understanding of the transport properties in the vicinity of the electrodes is of
      technological importance. 

PMID- 25399136
TI  - Normal-ordered second-quantized Hamiltonian for molecular vibrations.
AB  - A normal-ordered second-quantized form of the Hamiltonian is derived for quantum
      dynamics in a bound potential energy surface expressed as a Taylor series in an
      arbitrary set of orthogonal, delocalized coordinates centered at an arbitrary
      geometry. The constant, first-, and second-order excitation amplitudes of this
      Hamiltonian are identified as the ground-state energy, gradients, and
      frequencies, respectively, of the size-extensive vibrational self-consistent
      field (XVSCF) method or the self-consistent phonon method. They display the well
      defined size dependence of V(1-n/2), where V is the volume and n is the number of
      coordinates associated with the amplitudes. It is used to rapidly derive the
      equations of XVSCF and vibrational many-body perturbation methods with the Moller
      Plesset partitioning of the Hamiltonian.

PMID- 25399137
TI  - Two-electron Rabi oscillations in real-time time-dependent density-functional
      theory.
AB  - We investigate the Rabi oscillations of electrons excited by an applied electric
      field in several simple molecular systems using time-dependent configuration
      interaction (TDCI) and real-time time-dependent density-functional theory (RT
      TDDFT) dynamics. While the TDCI simulations exhibit the expected single-electron
      Rabi oscillations at a single resonant electric field frequency, Rabi
      oscillations in the RT-TDDFT simulations are a two-electron process. The
      existence of two-electron Rabi oscillations is determined both by full population
      inversion between field-free molecular orbitals and the behavior of the
      instantaneous dipole moment during the simulations. Furthermore, the Rabi
      oscillations in RT-TDDFT are subject to an intensity threshold of the electric
      field, below which Rabi oscillations do not occur and above which the two
      electron Rabi oscillations occur at a broad range of frequencies. It is also
      shown that at field intensities near the threshold intensity, the field frequency
      predicted to induce Rabi oscillations by linear response TDDFT only produces
      detuned Rabi oscillations. Instead, the field frequency that yields the full two
      electron population inversion and Rabi oscillation behavior is shown to be the
      average of single-electron transition frequencies from the ground S0 state and
      the doubly-excited S2 state. The behavior of the two-electron Rabi oscillations
      is rationalized via two possible models. The first model is a multi-photon
      process that results from the electric field interacting with the three level
      system such that three level Rabi oscillations may occur. The second model
      suggests that the mean-field nature of RT-TDDFT induces paired electron
      propagation. 

PMID- 25399138
TI  - Metastability, spectrum, and eigencurrents of the Lennard-Jones-38 network.
AB  - We develop computational tools for spectral analysis of stochastic networks
      representing energy landscapes of atomic and molecular clusters. Physical meaning
      and some properties of eigenvalues, left and right eigenvectors, and
      eigencurrents are discussed. We propose an approach to compute a collection of
      eigenpairs and corresponding eigencurrents describing the most important
      relaxation processes taking place in the system on its way to the equilibrium. It
      is suitable for large and complex stochastic networks where pairwise transition
      rates, given by the Arrhenius law, vary by orders of magnitude. The proposed
      methodology is applied to the network representing the Lennard-Jones-38 cluster
      created by Wales's group. Its energy landscape has a double funnel structure with
      a deep and narrow face-centered cubic funnel and a shallower and wider
      icosahedral funnel. However, the complete spectrum of the generator matrix of the
      Lennard-Jones-38 network has no appreciable spectral gap separating the
      eigenvalue corresponding to the escape from the icosahedral funnel. We provide a
      detailed description of the escape process from the icosahedral funnel using the
      eigencurrent and demonstrate a superexponential growth of the corresponding
      eigenvalue. The proposed spectral approach is compared to the methodology of the
      Transition Path Theory. Finally, we discuss whether the Lennard-Jones-38 cluster
      is metastable from the points of view of a mathematician and a chemical
      physicist, and make a connection with experimental works. 

PMID- 25399139
TI  - Tuning the smooth particle mesh Ewald sum: application on ionic solutions and
      dipolar fluids.
AB  - Numerical properties of the smooth particle mesh Ewald (SPME) sum [U. Essmann, L.
      Perera, M. L. Berkowitz, T. Darden, H. Lee, and L. G. Pedersen, J. Chem. Phys.
      103, 8577 (1995)] have been investigated by molecular dynamics simulation of
      ionic solutions and dipolar fluids. Scaling dependence of execution time on the
      number of particles at optimal performance have been determined and compared with
      the corresponding data of the standard Ewald (SE) sum. For both types of systems
      and over the range from N = 10(3) to 10(5) particles, the SPME sum displays a sub
      O(N ln N) complexity, whereas the SE sum possesses an O(N(3/2)) complexity. The
      breakeven of the simulation times appears at O(10(3)) particles, and the SPME sum
      is ~20 times faster than the SE sum at 10(5) particles. Furthermore, energy
      truncation error and the energy and force execution time of the reciprocal space
      evaluation as function of the number of particles and the convergence parameters
      of the SPME sum have been determined for both types of systems containing up to
      10(6) particles. 

PMID- 25399140
TI  - 2D-Raman-THz spectroscopy: a sensitive test of polarizable water models.
AB  - In a recent paper, the experimental 2D-Raman-THz response of liquid water at
      ambient conditions has been presented [J. Savolainen, S. Ahmed, and P. Hamm,
      Proc. Natl. Acad. Sci. U. S. A. 110, 20402 (2013)]. Here, all-atom molecular
      dynamics simulations are performed with the goal to reproduce the experimental
      results. To that end, the molecular response functions are calculated in a first
      step, and are then convoluted with the laser pulses in order to enable a direct
      comparison with the experimental results. The molecular dynamics simulation are
      performed with several different water models: TIP4P/2005, SWM4-NDP, and TL4P. As
      polarizability is essential to describe the 2D-Raman-THz response, the TIP4P/2005
      water molecules are amended with either an isotropic or a anisotropic
      polarizability a posteriori after the molecular dynamics simulation. In contrast,
      SWM4-NDP and TL4P are intrinsically polarizable, and hence the 2D-Raman-THz
      response can be calculated in a self-consistent way, using the same force field
      as during the molecular dynamics simulation. It is found that the 2D-Raman-THz
      response depends extremely sensitively on details of the water model, and in
      particular on details of the description of polarizability. Despite the limited
      time resolution of the experiment, it could easily distinguish between various
      water models. Albeit not perfect, the overall best agreement with the
      experimental data is obtained for the TL4P water model. 

PMID- 25399141
TI  - The HCO+-H2 van der Waals interaction: potential energy and scattering.
AB  - We compute the rigid-body, four-dimensional interaction potential between HCO(+)
      and H2. The ab initio energies are obtained at the coupled-cluster single double
      triple level of theory, corrected for Basis Set Superposition Errors. The ab
      initio points are fit onto the spherical basis relevant for quantum scattering.
      We present elastic and rotationally inelastic coupled channels scattering between
      low lying rotational levels of HCO(+) and para-/ortho-H2. Results are compared
      with similar earlier computations with He or isotropic para-H2 as the projectile.
      Computations agree with earlier pressure broadening measurements. 

PMID- 25399142
TI  - Energy transfer models in nitrogen plasmas: analysis of N2(X1Sigmag+)-N(4S(u))-e-
      interaction.
AB  - The relaxation of N2(X1Sigmag+) molecules in a background gas composed of
      N((4)S(u)) atoms and free electrons is studied by using an ideal isochoric and
      isothermic chemical reactor. A rovibrational state-to-state model is developed to
      study energy transfer process induced by free electron and atomic collisions. The
      required cross sections and the corresponding rate coefficients are taken from
      two well-known kinetic databases: NASA Ames kinetic mechanism for the description
      of the N2(X1Sigmag+)-N((4)S(u)) processes and the Phys4Entry database for the
      electron driven processes, N2(X1Sigmag+)-e(-). The evolution of the population
      densities of each individual rovibrational level is explicitly determined via the
      numerical solution of the master equation for temperatures ranging from 10000 to
      30,000 K. It was found that the distribution of the rovibrational energy levels
      of N2(X1Sigmag+) is strongly influenced by the electron driven collisional
      processes, which promote the excitation of the low lying vibrational levels. The
      macroscopic vibrational energy relaxation is governed by the molecule-atom
      collisions, when free electrons, initially cold are relaxing to the final heat
      bath temperature. Thus, the main role of the free electrons is to ensure the
      equilibration of vibrational and free electron excitation, thus validating the
      existence of the local equilibrium T(V)-T(e). However, if electrons and heavy
      particles are assumed to be in equilibrium at the heat bath temperature, electron
      driven processes dominate the vibrational relaxation. Finally, we have assessed
      the validity of the Landau-Teller model for the description of the inelastic
      energy transfer between molecules and free electrons. In the case of free
      electron temperatures lower than 10,000 K, Landau-Teller relaxation model gives
      an accurate description of the vibrational relaxation, while at higher
      temperatures the error in the predictions can be significant and the model should
      not be used.

PMID- 25399143
TI  - Laboratory detections of SiC2N and SiC3N by Fourier transform microwave
      spectroscopy.
AB  - Two silicon-bearing carbon chain radicals, SiC2N and SiC3N, were detected in the
      laboratory by Fourier transform microwave spectroscopy. Molecular constants
      including the hyperfine coupling constants have been determined for the two
      radicals in the ground electronic states. The SiC2N and SiC3N radicals have
      linear structures in the (2)Pi ground electronic states with inverted and regular
      fine structures, respectively, as are the cases for their isoelectronic radicals,
      SiC3H and SiC4H, indicating that the SiC(n)N radicals have similar electronic
      structures to the SiC(n +1)H radicals. The electronic structures of SiC2N and
      SiC3N in the ground states are discussed on the basis of the experimentally
      determined molecular constants.

PMID- 25399144
TI  - Noble gas encapsulation into carbon nanotubes: predictions from analytical model
      and DFT studies.
AB  - The energetics for the interaction of the noble gas atoms with the carbon
      nanotubes (CNTs) are investigated using an analytical model and density
      functional theory calculations. Encapsulation of the noble gas atoms, He, Ne, Ar,
      Kr, and Xe into CNTs of various chiralities is studied in detail using an
      analytical model, developed earlier by Hill and co-workers. The constrained
      motion of the noble gas atoms along the axes of the CNTs as well as the off-axis
      motion are discussed. Analyses of the forces, interaction energies, acceptance
      and suction energies for the encapsulation enable us to predict the optimal CNTs
      that can encapsulate each of the noble gas atoms. We find that CNTs of radii 2.98
      - 4.20 A (chiral indices, (5,4), (6,4), (9,1), (6,6), and (9,3)) can efficiently
      encapsulate the He, Ne, Ar, Kr, and Xe atoms, respectively. Endohedral adsorption
      of all the noble gas atoms is preferred over exohedral adsorption on various
      CNTs. The results obtained using the analytical model are subsequently compared
      with the calculations performed with the dispersion-including density functional
      theory at the M06 - 2X level using a triple-zeta basis set and good qualitative
      agreement is found. The analytical model is however found to be computationally
      cheap as the equations can be numerically programmed and the results obtained in
      comparatively very less time. 

PMID- 25399145
TI  - Fully quantal calculation of H2 translation-rotation states in the (p
      H2)2@5(12)6(4) clathrate hydrate inclusion compound.
AB  - The quantal translation-rotation (TR) states of the (p-H2)2@5(12)6(4) clathrate
      hydrate inclusion compound have been computed. The ten-dimensional problem (in
      the rigid-cage and rigid-H2 approximation) is solved by first approximating the
      H2 moieties as spherically symmetric and solving for their 6D translational
      eigenstates. These are then combined with H2 free rotational states in a product
      basis that is used to diagonalize the full TR hamiltonian. The computed low
      energy eigenstates have translational components that are essentially identical
      to the 6D translational eigenstates and rotational components that are 99.9%
      composed of rotationally unexcited H2 moieties. In other words, TR coupling is
      minimal for the low-energy states of the species. The low-energy level structure
      is found to be substantially more congested than that of the more tightly packed
      (p-H2)4@5(12)6(4) clathrate species. The level structure is also shown to be
      understandable in terms of a model of (H2)2 as a semirigid diatomic species
      consisting of two spherically symmetric H2 pseudo-atoms. 

PMID- 25399146
TI  - Line mixing effects in isotropic Raman spectra of pure N2: a classical trajectory
      study.
AB  - Line mixing effects in the Q branch of pure N2 isotropic Raman scattering are
      studied at room temperature using a classical trajectory method. It is the first
      study using an extended modified version of Gordon's classical theory of impact
      broadening and shift of rovibrational lines. The whole relaxation matrix is
      calculated using an exact 3D classical trajectory method for binary collisions of
      rigid N2 molecules employing the most up-to-date intermolecular potential energy
      surface (PES). A simple symmetrizing procedure is employed to improve off
      diagonal cross-sections to make them obeying exactly the principle of detailed
      balance. The adequacy of the results is confirmed by the sum rule. The comparison
      is made with available experimental data as well as with benchmark fully quantum
      close coupling [F. Thibault, C. Boulet, and Q. Ma, J. Chem. Phys. 140, 044303
      (2014)] and refined semi-classical Robert-Bonamy [C. Boulet, Q. Ma, and F.
      Thibault, J. Chem. Phys. 140, 084310 (2014)] results. All calculations
      (classical, quantum, and semi-classical) were made using the same PES. The
      agreement between classical and quantum relaxation matrices is excellent, opening
      the way to the analysis of more complex molecular systems. 

PMID- 25399147
TI  - High-resolution laser spectroscopy and magnetic effect of the B2E' <- X2A2'
      transition of 14NO3 radical.
AB  - Rotationally resolved high-resolution fluorescence excitation spectra of (14)NO3
      radical have been observed for the 662 nm band, which is assigned as the 0-0 band
      of the B(2)E' <-X(2)A2' transition, by crossing a single-mode laser beam
      perpendicularly to a collimated molecular beam. More than 3000 rotational lines
      were detected in 15,070-15,145 cm(-1) region, but it is difficult to find the
      rotational line series. Remarkable rotational line pairs, whose interval is about
      0.0246 cm(-1), were found in the observed spectrum. This interval is the same
      amount with the spin-rotation splitting of the X(2)A2' (upsilon = 0, k = 0, N =
      1) level. From this interval and the observed Zeeman splitting up to 360 G, seven
      line pairs were assigned as the transitions to the (2)E'(3/2) (J' = 1.5) levels
      and 15 line pairs were assigned as the transitions to the (2)E'(1/2) (J' = 0.5)
      levels. From the rotational analysis, we recognized that the (2)E' state splits
      into (2)E'(3/2) and (2)E'(1/2) by the spin-orbit interaction and the effective
      spin-orbit interaction constant was roughly estimated as -21 cm(-1). From the
      number of the rotational line pairs, we concluded that the complicated rotational
      structure of this 662 nm band of (14)NO3 mainly owes to the vibronic interaction
      between the B(2)E' state and the dark A(2)E" state through the a2" symmetry
      vibrational mode.

PMID- 25399148
TI  - Phthalocyanine adsorption to graphene on Ir(111): evidence for decoupling from
      vibrational spectroscopy.
AB  - Phthalocyanine molecules have been adsorbed to Ir(111) and to graphene on
      Ir(111). From a comparison of scanning tunneling microscopy images of individual
      molecules adsorbed to the different surfaces alone it is difficult to discern
      potential differences in the molecular adsorption geometry. In contrast,
      vibrational spectroscopy using inelastic electron scattering unequivocally hints
      at strong molecule deformations on Ir(111) and at a planar adsorption geometry on
      graphene. The spectroscopic evidence for the different adsorption configurations
      is supported by density functional calculations. 

PMID- 25399149
TI  - Extended Fourier-transform spectroscopy studies and deperturbation analysis of
      the spin-orbit coupled A1Sigma+ and b3Pi states in RbCs.
AB  - The article presents a study of the strongly spin-orbit coupled singlet
      A(1)Sigma(+) and triplet b(3)Pi states of the RbCs molecule, which provide an
      efficient optical path to transfer ultracold molecules to their rovibrational
      ground state. Fourier-transform A(1)Sigma(+) - b(3)Pi -> X(1)Sigma(+) and
      (4)(1)Sigma(+) -> A(1)Sigma(+) - b(3)Pi laser-induced fluorescence (LIF) spectra
      were recorded for the natural mixture of the (85)Rb(133)Cs and (87)Rb(133)Cs
      isotopologues produced in a heat pipe oven. Overall 8730 rovibronic term values
      of A(1)Sigma(+) and b(3)Pi states were determined with an uncertainty of 0.01 cm(
      1) in the energy range [9012, 14087] cm(-1), covering rotational quantum numbers
      J ? [6, 324]. An energy-based deperturbation analysis performed in the framework
      of the four A(1)Sigma(+) - b(3)Pi(Omega = 0, 1, 2) coupled-channels approach
      reproduces 97% of the experimental term values of both isotopologues with a
      standard deviation of 0.0036 cm(-1). The reliability of the deperturbed mass
      invariant potentials and spin-orbit coupling functions of the interacting
      A(1)Sigma(+) and b(3)Pi states is additionally proved by a good reproduction of
      the A - b -> X and (4)(1)Sigma(+) -> A - b relative intensity distributions. The
      achieved accuracy of the A - b complex description allowed us to use the latter
      to assign the observed (5)(1)Sigma(+) -> A - b and (3)(1)Pi -> A - b transitions.
      As is demonstrated, LIF to the A - b complex becomes as informative as to the
      ground X(1)Sigma(+) state, which is confirmed by comparing the results of
      (4)(1)Sigma(+) state analysis based on (4)(1)Sigma(+) -> A - b LIF with the data
      from V. Zuters et al. [Phys. Rev. A 87, 022504 (2013)] based on (4)(1)Sigma(+) ->
      X LIF.

PMID- 25399150
TI  - Photodissociation of OCS: deviations between theory and experiment, and the
      importance of higher order correlation effects.
AB  - The photodissociation of carbonyl sulfide (OCS) was investigated theoretically in
      a series of studies by Schmidt and co-workers. Initial studies [J. A. Schmidt, M.
      S. Johnson, G. C. McBane, and R. Schinke, J. Chem. Phys. 136, 131101 (2012); J.
      A. Schmidt, M. S. Johnson, G. C. McBane, and R. Schinke, J. Chem. Phys. 137,
      054313 (2012)] found photodissociation in the first UV-band to occur mainly by
      excitation of the 2(1)A' (A) excited state. However, in a later study [G. C.
      McBane, J. A. Schmidt, M. S. Johnson, and R. Schinke, J. Chem. Phys. 138, 094314
      (2013)] it was found that a significant fraction of photodissociation must occur
      by excitation of 1(1)A" (B) excited state to explain the product angular
      distribution. The branching between excitation of the A and B excited states is
      determined by the magnitude of the transition dipole moment vectors in the Franck
      Condon region. This study examines the sensitivity of these quantities to changes
      in the employed electronic structure methodology. This study benchmarks the
      methodology employed in previous studies against highly correlated electronic
      structure methods (CC3 and MRAQCC) and provide evidence in support of the picture
      of the OCS photodissociation process presented in [G. C. McBane, J. A. Schmidt,
      M. S. Johnson, and R. Schinke, J. Chem. Phys. 138, 094314 (2013)] showing that
      excitation of A and B electronic states both contribute significantly to the
      first UV absorption band of OCS. In addition, this study presents evidence in
      support of the assertion that the A state potential energy surface employed in
      previous studies underestimates the energy at highly bent geometries (gamma ~ 70
      degrees ) leading to overestimated rotational energy in the product CO.

PMID- 25399151
TI  - Theoretical determination of anisotropic thermal conductivity for initially
      defect-free and defective TATB single crystals.
AB  - The anisotropic thermal conductivity was determined for initially defect-free and
      defective crystals of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), a material
      that exhibits a graphitic-like packing structure with stacked single-molecule
      thick layers, using the reverse non-equilibrium molecular dynamics method and an
      established TATB molecular dynamics force field. Thermal conduction in TATB is
      predicted to be substantially higher and more anisotropic than in other related
      organic molecular explosives, with conduction along directions nominally in the
      plane of the molecular layers at least 68% greater than conduction along the
      direction exactly perpendicular to the layers. Finite-size effects along the
      conduction directions were assessed. The conductivity along directions nominally
      in the plane of the molecular layers was found to be insensitive to the supercell
      length along the conduction direction-a result commensurate with the estimated
      phonon mean free path, ~6 A. A small decrease in the conductivity normal to the
      layers was found for longer supercells and is likely due to increased phonon
      scattering as a result of dynamic structural transitions in the crystal. The
      thermal conductivity of TATB crystals containing vacancy defects was also
      determined and the variation of conductivity with crystal density was found to be
      both linear and anisotropic, with the introduction of vacancy defects leading to
      a greater percentage reduction in conduction for the direction perpendicular to
      the molecular layers. 

PMID- 25399152
TI  - Hexatic phase and cluster crystals of two-dimensional GEM4 spheres.
AB  - Two-dimensional crystals of classical particles are very peculiar in that melting
      may occur in two steps, in a continuous fashion, via an intermediate hexatic
      fluid phase exhibiting quasi-long-range orientational order. On the other hand,
      three-dimensional spheres repelling each other through a fast-decaying bounded
      potential of generalized-exponential shape (GEM4 potential) can undergo freezing
      into cluster crystals, allowing for more that one particle per lattice site. We
      hereby study the combined effect of low spatial dimensionality and extreme
      potential softness, by investigating the phase behavior of the two-dimensional
      (2D) GEM4 system. Using a combination of density-functional theory and numerical
      free-energy calculations, we show that the 2D GEM4 system displays one ordinary
      and several cluster triangular-crystal phases, and that only the ordinary crystal
      first melts into a hexatic phase. Upon heating, the difference between the
      various cluster crystals fades away, eventually leaving a single undifferentiated
      cluster phase with a pressure-modulated site occupancy. 

PMID- 25399153
TI  - Effect of dispersive long-range corrections to the pressure tensor: the vapour
      liquid interfacial properties of the Lennard-Jones system revisited.
AB  - We propose an extension of the improved version of the inhomogeneous long-range
      corrections of Janecek [J. Phys. Chem. B 110, 6264-6269 (2006)], presented
      recently by MacDowell and Blas [J. Chem. Phys. 131, 074705 (2009)] to account for
      the intermolecular potential energy of spherical, rigid, and flexible molecular
      systems, to deal with the contributions to the microscopic components of the
      pressure tensor due to the dispersive long-range corrections. We have performed
      Monte Carlo simulations in the canonical ensemble to obtain the interfacial
      properties of spherical Lennard-Jones molecules with different cutoff distances,
      r(c) = 2.5, 3, 4, and 5sigma. In addition, we have also considered cutoff
      distances r(c) = 2.5 and 3sigma in combination with the inhomogeneous long-range
      corrections proposed in this work. The normal and tangential microscopic
      components of the pressure tensor are obtained using the mechanical or virial
      route in combination with the recipe of Irving and Kirkwood, while the
      macroscopic components are calculated using the Volume Perturbation thermodynamic
      route proposed by de Miguel and Jackson [J. Chem. Phys. 125, 164109 (2006)]. The
      vapour-liquid interfacial tension is evaluated using three different procedures,
      the Irving-Kirkwood method, the difference between the macroscopic components of
      the pressure tensor, and the Test-Area methodology. In addition to the pressure
      tensor and the surface tension, we also obtain density profiles, coexistence
      densities, vapour pressure, critical temperature and density, and interfacial
      thickness as functions of temperature, paying particular attention to the effect
      of the cutoff distance and the long-range corrections on these properties.
      According to our results, the main effect of increasing the cutoff distance (at
      fixed temperature) is to sharpen the vapour-liquid interface, to decrease the
      vapour pressure, and to increase the width of the biphasic coexistence region. As
      a result, the interfacial thickness decreases, the width of the tangential
      microscopic component of the pressure tensor profile increases, and the surface
      tension increases as the cutoff distance is larger. We have also checked the
      effect of the impulsive contribution to the pressure due to the discontinuity of
      the intermolecular interaction potential when it is cut. If this contribution is
      not accounted for in the calculation of the microscopic components of the
      pressure tensor, incorrect values of both components as well as a wrong structure
      along the vapour-liquid interface are obtained.

PMID- 25399154
TI  - Structure of spherical electric double layers with fully asymmetric electrolytes:
      a systematic study by Monte Carlo simulations and density functional theory.
AB  - A systematic investigation of the spherical electric double layers with the
      electrolytes having size as well as charge asymmetry is carried out using density
      functional theory and Monte Carlo simulations. The system is considered within
      the primitive model, where the macroion is a structureless hard spherical
      colloid, the small ions as charged hard spheres of different size, and the
      solvent is represented as a dielectric continuum. The present theory approximates
      the hard sphere part of the one particle correlation function using a weighted
      density approach whereas a perturbation expansion around the uniform fluid is
      applied to evaluate the ionic contribution. The theory is in quantitative
      agreement with Monte Carlo simulation for the density and the mean electrostatic
      potential profiles over a wide range of electrolyte concentrations, surface
      charge densities, valence of small ions, and macroion sizes. The theory provides
      distinctive evidence of charge and size correlations within the electrode
      electrolyte interface in spherical geometry. 

PMID- 25399155
TI  - Does surface roughness amplify wetting?
AB  - Any solid surface is intrinsically rough on the microscopic scale. In this paper,
      we study the effect of this roughness on the wetting properties of hydrophilic
      substrates. Macroscopic arguments, such as those leading to the well-known
      Wenzel's law, predict that surface roughness should amplify the wetting
      properties of such adsorbents. We use a fundamental measure density functional
      theory to demonstrate the opposite effect from roughness for microscopically
      corrugated surfaces, i.e., wetting is hindered. Based on three independent
      analyses we show that microscopic surface corrugation increases the wetting
      temperature or even makes the surface hydrophobic. Since for macroscopically
      corrugated surfaces the solid texture does indeed amplify wetting there must
      exist a crossover between two length-scale regimes that are distinguished by
      opposite response on surface roughening. This demonstrates how deceptive can be
      efforts to extend the thermodynamical laws beyond their macroscopic territory. 

PMID- 25399156
TI  - Insights into DNA-mediated interparticle interactions from a coarse-grained
      model.
AB  - DNA-functionalized particles have great potential for the design of complex self
      assembled materials. The major hurdle in realizing crystal structures from DNA
      functionalized particles is expected to be kinetic barriers that trap the system
      in metastable amorphous states. Therefore, it is vital to explore the molecular
      details of particle assembly processes in order to understand the underlying
      mechanisms. Molecular simulations based on coarse-grained models can provide a
      convenient route to explore these details. Most of the currently available coarse
      grained models of DNA-functionalized particles ignore key chemical and structural
      details of DNA behavior. These models therefore are limited in scope for studying
      experimental phenomena. In this paper, we present a new coarse-grained model of
      DNA-functionalized particles which incorporates some of the desired features of
      DNA behavior. The coarse-grained DNA model used here provides explicit DNA
      representation (at the nucleotide level) and complementary interactions between
      Watson-Crick base pairs, which lead to the formation of single-stranded hairpin
      and double-stranded DNA. Aggregation between multiple complementary strands is
      also prevented in our model. We study interactions between two DNA-functionalized
      particles as a function of DNA grafting density, lengths of the hybridizing and
      non-hybridizing parts of DNA, and temperature. The calculated free energies as a
      function of pair distance between particles qualitatively resemble experimental
      measurements of DNA-mediated pair interactions. 

PMID- 25399157
TI  - Diffusion and surface excess of a confined nanoswimmer dispersion.
AB  - The diffusivity and surface excess of nanoswimmers which are confined in two
      plates with the separation H are explored by dissipative particle dynamics. Both
      mean squared displacement and velocity autocorrelation function methods are used
      to study the diffusive behavior of nanoswimmers with the Brownian diffusivity D0
      and the results obtained from both methods are consistent. The active diffusivity
      of confined nanoswimmers (D - D0) depends on the wall separation, swimming speed
      v(a), and run time tau. Our simulation results show that (D-D0)/v(a)(2)tau is a
      function of v(a)tau/H. The reduction in the diffusivity of active colloids is
      more significant than that of passive particles. The distribution of nanoswimmers
      between two parallel walls is acquired and two regions can be identified. The
      accumulation of nanoswimmers near walls is quantitatively described by the
      surface excess Gamma. It is found that Gamma grows as the nanoswimmer
      concentration c(b), swimming speed v(a), and run time tau are increased. The
      coupling between the ballistic trajectory of nanoswimmers and the walls results
      in nanoswimmer accumulation. The simulation outcomes indicate that Gamma/Hc(b) is
      a function of H/v(a)tau.

PMID- 25399158
TI  - Phase diagrams of mixtures of a polymer and a cholesteric liquid crystal under an
      external field.
AB  - We present a mean field theory to describe phase behaviors in mixtures of a
      polymer and a cholesteric liquid crystal under an external magnetic or electric
      field. Taking into account a chiral coupling between a polymer and a liquid
      crystal under the external field, we examine twist-untwist phase transitions and
      phase separations in the mixtures. It is found that a cholesteric-nematic phase
      transition can be induced by not only the external field but also concentration
      and temperature. Depending on the strength of the external field, we predict
      cholesteric-paranematic (Ch+pN), nematic-paranematic (N+pN), cholesteric-nematic
      (Ch+N) phase separations, etc., on the temperature-concentration plane. We also
      discuss mixtures of a non-chiral nematic liquid crystal and a chiral dopant. 

PMID- 25399159
TI  - Damage in spherical cellular membrane generated by the shock waves: coarse
      grained molecular dynamics simulation of lipid vesicle.
AB  - Traumatic Brain Injury is a major health issue that is hard to diagnose since it
      often occurs without signs of external injuries. While it is well known that
      exposure of biological cells to shock waves causes damage to the cell membrane,
      it is currently unknown by which mechanisms damage is caused, and how it depends
      on physical parameters such as shock wave velocity, shock pulse duration, or
      shock pulse shape. In this computational study, we use a coarse-grained model of
      the lipid vesicle as a generic model of a cell membrane to elucidate the general
      principles of the cellular damage induced by the shock wave direct passage
      through the cranium. Results indicate that the extent of the liposome compression
      does not strongly depend on the pressure pulse and that liposome extension is
      very sensitive to the change in the negative pressure phase. The structural
      integrity of the vesicle is altered as pores form in the lipid membrane at
      overall pressure impulses generated by supersonic shock waves, which are greater
      than 5 Pa.s at single or repetitive exposure. Consequently, these permeability
      changes may lead to changes in the influx of sodium, potassium, and calcium ions.

PMID- 25399160
TI  - Vitrification in a wide cooling rate range: the relations between cooling rate,
      relaxation time, transition width, and fragility.
AB  - The cooling rate dependence of the thermal glass transition of polystyrene (PS)
      is measured in a range between 0.2 K/min (0.003 K/s) and 4000 K/s using
      conventional differential scanning calorimetry (DSC) and Fast Scanning
      Calorimetry (Flash DSC 1). The cooling rate dependence of the thermal glass
      transition can be described in an analogy to the frequency dependence of the
      dynamic glass transition. The relation between cooling rate, beta(c), and
      frequency, omega, is usually described by the Frenkel-Kobeko-Reiner-(FKR)
      hypothesis beta(c)/omega = C, where C is a constant. We have introduced a new
      property to describe the kinetics of the vitrification process; the vitrification
      function, kappa. This function is the ratio between the width of the thermal and
      dynamic glass transition. The validity of the FKR hypothesis is analyzed by two
      independent methods, the analysis of the activation diagram using the Vogel
      Fulcher-Tammann-Hesse equation and the analysis of the temperature dependence of
      the transition width. We derived a relation for the FKR-constant, which indicates
      the validity range of the FKR hypotheses. This hypothesis is valid if the
      logarithmic width of the vitrified and the non-vitrified relaxation spectrum is
      temperature invariant. This condition is fulfilled for polystyrene in the
      measured cooling rate range. Furthermore we discuss the relation between the
      vitrification function, the transition width, the FKR constant, and the
      fragility.

PMID- 25399161
TI  - Theoretical analysis of geometry and NMR isotope shift in hydrogen-bonding center
      of photoactive yellow protein by combination of multicomponent quantum mechanics
      and ONIOM scheme.
AB  - Multicomponent quantum mechanical (MC_QM) calculation has been extended with
      ONIOM (our own N-layered integrated molecular orbital + molecular mechanics)
      scheme [ONIOM(MC_QM:MM)] to take account of both the nuclear quantum effect and
      the surrounding environment effect. The authors have demonstrated the first
      implementation and application of ONIOM(MC_QM:MM) method for the analysis of the
      geometry and the isotope shift in hydrogen-bonding center of photoactive yellow
      protein. ONIOM(MC_QM:MM) calculation for a model with deprotonated Arg52
      reproduced the elongation of O-H bond of Glu46 observed by neutron diffraction
      crystallography. Among the unique isotope shifts in different conditions, the
      model with protonated Arg52 with solvent effect reasonably provided the best
      agreement with the corresponding experimental values from liquid NMR measurement.
      Our results implied the availability of ONIOM(MC_QM:MM) to distinguish the local
      environment around hydrogen bonds in a biomolecule. 

PMID- 25399162
TI  - Influence of intra-pigment vibrations on dynamics of photosynthetic exciton.
AB  - We have numerically investigated the effect of an underdamped intra-pigment
      vibrational mode on an exciton's quantum coherence and energy transfer
      efficiency. Our model describes a bacteriochlorophyll a pigment-protein dimer
      under the conditions at which photosynthetic energy transfer occurs. The dimer is
      modeled using a theoretical treatment of a vibronic exciton, and its dynamics are
      numerically analyzed using a non-Markovian and non-perturbative method. We
      examined the system's response to various values of the Huang-Rhys factor, site
      energy difference, reorganization energy, and reorganization energy difference.
      We found that the inclusion of the intra-pigment vibronic mode allows for long
      lived oscillatory quantum coherences to occur. This excitonic coherence is robust
      against static site-energy disorder. The vibrational mode also promotes exciton
      transfer along the site-energy landscape thus improving the overall energy
      transfer efficiency. 

PMID- 25399165
TI  - Preface: special topic on interfacial and confined water.
AB  - This special topic on the chemical physics of interfacial and confined water
      contains a collection of original research papers that showcase recent
      theoretical and experimental advances in the field. These papers provide a timely
      discussion of fundamental aspects of interfacial and confined water that are
      important in both natural environments and engineered applications. 

PMID- 25399166
TI  - Hydrophobic hydration driven self-assembly of curcumin in water: similarities to
      nucleation and growth under large metastability, and an analysis of water
      dynamics at heterogeneous surfaces.
AB  - As the beneficial effects of curcumin have often been reported to be limited to
      its small concentrations, we have undertaken a study to find the aggregation
      properties of curcumin in water by varying the number of monomers. Our molecular
      dynamics simulation results show that the equilibrated structure is always an
      aggregated state with remarkable structural rearrangements as we vary the number
      of curcumin monomers from 4 to 16 monomers. We find that the curcumin monomers
      form clusters in a very definite pattern where they tend to aggregate both in
      parallel and anti-parallel orientation of the phenyl rings, often seen in the
      formation of beta-sheet in proteins. A considerable enhancement in the population
      of parallel alignments is observed with increasing the system size from 12 to 16
      curcumin monomers. Due to the prevalence of such parallel alignment for large
      system size, a more closely packed cluster is formed with maximum number of
      hydrophobic contacts. We also follow the pathway of cluster growth, in particular
      the transition from the initial segregated to the final aggregated state. We find
      the existence of a metastable structural intermediate involving a number of
      intermediate-sized clusters dispersed in the solution. We have constructed a free
      energy landscape of aggregation where the metatsable state has been identified.
      The course of aggregation bears similarity to nucleation and growth in highly
      metastable state. The final aggregated form remains stable with the total
      exclusion of water from its sequestered hydrophobic core. We also investigate
      water structure near the cluster surface along with their orientation. We find
      that water molecules form a distorted tetrahedral geometry in the 1st solvation
      layer of the cluster, interacting rather strongly with the hydrophilic groups at
      the surface of the curcumin. The dynamics of such quasi-bound water molecules
      near the surface of curcumin cluster is considerably slower than the bulk
      signifying a restricted motion as often found in protein hydration layer. 

PMID- 25399167
TI  - Theoretical vibrational sum-frequency generation spectroscopy of water near lipid
      and surfactant monolayer interfaces.
AB  - Understanding the structure of water near cell membranes is crucial for
      characterizing water-mediated events such as molecular transport. To obtain
      structural information of water near a membrane, it is useful to have a surface
      selective technique that can probe only interfacial water molecules. One such
      technique is vibrational sum-frequency generation (VSFG) spectroscopy. As model
      systems for studying membrane headgroup/water interactions, in this paper we
      consider lipid and surfactant monolayers on water. We adopt a theoretical
      approach combining molecular dynamics simulations and phase-sensitive VSFG to
      investigate water structure near these interfaces. Our simulated spectra are in
      qualitative agreement with experiments and reveal orientational ordering of
      interfacial water molecules near cationic, anionic, and zwitterionic interfaces.
      OH bonds of water molecules point toward an anionic interface leading to a
      positive VSFG peak, whereas the water hydrogen atoms point away from a cationic
      interface leading to a negative VSFG peak. Coexistence of these two interfacial
      water species is observed near interfaces between water and mixtures of cationic
      and anionic lipids, as indicated by the presence of both negative and positive
      peaks in their VSFG spectra. In the case of a zwitterionic interface, OH
      orientation is toward the interface on the average, resulting in a positive VSFG
      peak. 

PMID- 25399168
TI  - A direct evidence of vibrationally delocalized response at ice surface.
AB  - Surface-specific vibrational spectroscopic responses at isotope diluted ice and
      amorphous ice are investigated by molecular dynamics (MD) simulations combined
      with quantum mechanics/molecular mechanics calculations. The intense response
      specific to the ordinary crystal ice surface is predicted to be significantly
      suppressed in the isotopically diluted and amorphous ices, demonstrating the
      vibrational delocalization at the ordinary ice surface. The collective vibration
      at the ice surface is also analyzed with varying temperature by the MD
      simulation. 

PMID- 25399169
TI  - Thermodynamic properties of bulk and confined water.
AB  - The thermodynamic response functions of water display anomalous behaviors. We
      study these anomalous behaviors in bulk and confined water. We use nuclear
      magnetic resonance (NMR) to examine the configurational specific heat and the
      transport parameters in both the thermal stable and the metastable supercooled
      phases. The data we obtain suggest that there is a behavior common to both
      phases: that the dynamics of water exhibit two singular temperatures belonging to
      the supercooled and the stable phase, respectively. One is the dynamic fragile-to
      strong crossover temperature (T(L) ? 225 K). The second, T* ~ 315 +/- 5 K, is a
      special locus of the isothermal compressibility K(T)(T, P) and the thermal
      expansion coefficient alpha(P)(T, P) in the P-T plane. In the case of water
      confined inside a protein, we observe that these two temperatures mark,
      respectively, the onset of protein flexibility from its low temperature glass
      state (T(L)) and the onset of the unfolding process (T*).

PMID- 25399170
TI  - Premelting, fluctuations, and coarse-graining of water-ice interfaces.
AB  - Using statistical field theory supplemented with molecular dynamics simulations,
      we consider premelting on the surface of ice as a generic consequence of broken
      hydrogen bonds at the boundary between the condensed and gaseous phases. A
      procedure for coarse-graining molecular configurations onto a continuous scalar
      order parameter field is discussed, which provides a convenient representation of
      the interface between locally crystal-like and locally liquid-like regions. A
      number of interfacial properties are straightforwardly evaluated using this
      procedure such as the average premelting thickness and surface tension. The
      temperature and system size dependence of the premelting layer thickness
      calculated in this way confirms the characteristic logarithmic growth expected
      for the scalar field theory that the system is mapped onto through coarse
      graining, though remains finite due to long-ranged interactions. Finally, from
      explicit simulations the existence of a premelting layer is shown to be
      insensitive to bulk lattice geometry, exposed crystal face, and curvature. 

PMID- 25399171
TI  - CO2 and C2H2 in cold nanodroplets of oxygenated organic molecules and water.
AB  - Recent demonstrations of subsecond and microsecond timescales for formation of
      clathrate hydrate nanocrystals hint at future methods of control of environmental
      and industrial gases such as CO2 and methane. Combined results from cold-chamber
      and supersonic-nozzle [A. S. Bhabhe, "Experimental study of condensation and
      freezing in a supersonic nozzle," Ph.D. thesis (Ohio State University, 2012),
      Chap. 7] experiments indicate extremely rapid encagement of components of all
      vapor pre-mixtures. The extreme rates are derived from (a) the all-vapor
      premixing of the gas-hydrate components and (b) catalytic activity of certain
      oxygenated organic large-cage guests. Premixing presents no obvious barrier to
      large-scale conditions of formation. Further, from sequential efforts of the
      groups of Trout and Buch, a credible defect-based model of the catalysis
      mechanism exists for guidance. Since the catalyst-generated defects are both
      mobile and abundant, it is often unnecessary for a high percentage of the cages
      to be occupied by a molecular catalyst. Droplets represent the liquid phase that
      bridges the premixed vapor and clathrate hydrate phases but few data exist for
      the droplets themselves. Here we describe a focused computational and FTIR
      spectroscopic effort to characterize the aerosol droplets of the all-vapor cold
      chamber methodology. Computational data for CO2 and C2H2, hetero-dimerized with
      each of the organic catalysts and water, closely match spectroscopic redshift
      patterns in both magnitude and direction. Though vibrational frequency shifts are
      an order of magnitude greater for the acetylene stretch mode, both CO2 and C2H2
      experience redshift values that increase from that for an 80% water-methanol
      solvent through the solvent series to approximately doubled values for
      tetrahydrofuran and trimethylene oxide (TMO) droplets. The TMO solvent properties
      extend to a 50 mol.% solution of CO2, more than an order of magnitude greater
      than for the water-methanol solvent mixture. The impressive agreement between
      heterodimer and experimental shift values throughout the two series encourages
      speculation concerning local droplet structures while the stable shift patterns
      appear to be useful indicators of the gas solubilities. 

PMID- 25399172
TI  - Reorientation of the "free OH" group in the top-most layer of air/water interface
      of sodium fluoride aqueous solution probed with sum-frequency generation
      vibrational spectroscopy.
AB  - Many experimental and theoretical studies have established the specific anion, as
      well as cation, effects on the hydrogen-bond structures at the air/water
      interface of electrolyte solutions. However, the ion effects on the top-most
      layer of the air/water interface, which is signified by the non-hydrogen-bonded
      so-called "free OH" group, have not been explicitly discussed or studied. In this
      report, we present the measurement of changes of the orientational angle of the
      "free OH" group at the air/water interface of the sodium fluoride (NaF) solutions
      at different concentrations using the interface selective sum-frequency
      generation vibrational spectroscopy (SFG-VS) in the ssp and ppp polarizations.
      The polarization dependent SFG-VS results show that the average tilt angle of the
      "free OH" changes from about 36.6 degrees  +/- 0.5 degrees  to 44.1 degrees  +/-
      0.6 degrees  as the NaF concentration increases from 0 to 0.94 M (nearly
      saturated). Such tilt angle change is around the axis of the other O-H group of
      the same water molecule at the top-most layer at the air/water interface that is
      hydrogen-bonded to the water molecules below the top-most layer. These results
      provide quantitative molecular details of the ion effects of the NaF salt on the
      structure of the water molecules at the top-most layer of the air/water
      interface, even though both the Na(+) cation and the F(-) anion are believed to
      be among the most excluded ions from the air/water interface. 

PMID- 25399173
TI  - Vapor deposition of water on graphitic surfaces: formation of amorphous ice,
      bilayer ice, ice I, and liquid water.
AB  - Carbonaceous surfaces are a major source of atmospheric particles and could play
      an important role in the formation of ice. Here we investigate through molecular
      simulations the stability, metastability, and molecular pathways of deposition of
      amorphous ice, bilayer ice, and ice I from water vapor on graphitic and atomless
      Lennard-Jones surfaces as a function of temperature. We find that bilayer ice is
      the most stable ice polymorph for small cluster sizes, nevertheless it can grow
      metastable well above its region of thermodynamic stability. In agreement with
      experiments, the simulations predict that on increasing temperature the outcome
      of water deposition is amorphous ice, bilayer ice, ice I, and liquid water. The
      deposition nucleation of bilayer ice and ice I is preceded by the formation of
      small liquid clusters, which have two wetting states: bilayer pancake-like
      (wetting) at small cluster size and droplet-like (non-wetting) at larger cluster
      size. The wetting state of liquid clusters determines which ice polymorph is
      nucleated: bilayer ice nucleates from wetting bilayer liquid clusters and ice I
      from non-wetting liquid clusters. The maximum temperature for nucleation of
      bilayer ice on flat surfaces, T(B)(max) is given by the maximum temperature for
      which liquid water clusters reach the equilibrium melting line of bilayer ice as
      wetting bilayer clusters. Increasing water-surface attraction stabilizes the
      pancake-like wetting state of liquid clusters leading to larger T(B)(max) for the
      flat non-hydrogen bonding surfaces of this study. The findings of this study
      should be of relevance for the understanding of ice formation by deposition mode
      on carbonaceous atmospheric particles, including soot.

PMID- 25399174
TI  - Is surface layering of aqueous alkali halides determined by ion pairing in the
      bulk solution?
AB  - This contribution aims to elucidate the connection between ion-ion-solvent
      interactions in the bulk of aqueous electrolyte solutions and the properties of
      their liquid-air interface. In particular, we were interested in the conditions
      under which ion pairs form at the surface and whether this is linked to ion
      pairing in the bulk. For this reason different combinations of hard (Cl(-),
      Li(+)) and soft ions (I(-), Cs(+)) were investigated. Ion hydration and possible
      ion association in the bulk was probed with dielectric relaxation spectroscopy.
      This technique monitors the cooperative reorientation of the dipolar solvent
      molecules and detects all ion-pair species possibly present in the solution. At
      the interface, the formation of contact ion pairs was investigated by infrared
      visible-sum frequency spectroscopy (SFG). This nonlinear optical technique
      possesses an inherent surface specificity and can be used for the
      characterization of interfacial water. The intensity of the SFG-active
      vibrational stretching modes depends on the number of oriented water molecules.
      The electric field at the surface of a charged aqueous interface aligns the water
      dipoles, which in turn increases the SFG response. Hence, the enhancement of the
      oscillator strengths of the water vibrational modes can be used to draw some
      conclusions on the strengths and geometrical extension of the electric field. The
      formation of ion pairs at the interface reduces the intensity of the band
      associated with hydrogen-bonded water. The underlying theory is presented. The
      combined data show that there are no contact ion pairs in the bulk of the fluid
      and--at best--only small amounts of solvent shared ion pairs. On the other hand,
      the combination of hard/hard or soft/soft ions leads to the formation of ion
      pairs at the liquid-air interface.

PMID- 25399175
TI  - The boson peak of deeply cooled confined water reveals the existence of a low
      temperature liquid-liquid crossover.
AB  - The Boson peak of deeply cooled water confined in the pores of a silica xerogel
      is studied by inelastic neutron scattering at different hydration levels to
      separate the contributions from matrix, water on the pore surfaces and "internal"
      water. Our results reveal that at high hydration level, where the contribution
      from internal water is dominant, the temperature dependence of the Boson peak
      intensity shows an inflection point at about 225 K. The complementary use of
      differential scanning calorimetry to describe the thermodynamics of the system
      allows identifying the inflection point as the signature of a water liquid-liquid
      crossover. 

PMID- 25399176
TI  - Detecting vapour bubbles in simulations of metastable water.
AB  - The investigation of cavitation in metastable liquids with molecular simulations
      requires an appropriate definition of the volume of the vapour bubble forming
      within the metastable liquid phase. Commonly used approaches for bubble detection
      exhibit two significant flaws: first, when applied to water they often identify
      the voids within the hydrogen bond network as bubbles thus masking the signature
      of emerging bubbles and, second, they lack thermodynamic consistency. Here, we
      present two grid-based methods, the M-method and the V-method, to detect bubbles
      in metastable water specifically designed to address these shortcomings. The M
      method incorporates information about neighbouring grid cells to distinguish
      between liquid- and vapour-like cells, which allows for a very sensitive
      detection of small bubbles and high spatial resolution of the detected bubbles.
      The V-method is calibrated such that its estimates for the bubble volume
      correspond to the average change in system volume and are thus thermodynamically
      consistent. Both methods are computationally inexpensive such that they can be
      used in molecular dynamics and Monte Carlo simulations of cavitation. We
      illustrate them by computing the free energy barrier and the size of the critical
      bubble for cavitation in water at negative pressure. 

PMID- 25399177
TI  - The thermodynamics of proton hydration and the electrochemical surface potential
      of water.
AB  - The free energy change for transferring a single ion across the water
      liquid/vapor interface includes an electrochemical surface potential
      contribution. Since this potential is not directly accessible to thermodynamic
      measurement, several extra-thermodynamic approaches have been employed to infer
      its sign and magnitude, with a resulting wide spread of values. Here, we examine
      further the thermodynamics of proton hydration and the electrochemical surface
      potential of water along three directions: (1) a basic relation of interfacial
      electrostatics and experimental results on ion distributions near a water/organic
      interface are employed to infer a solvent contribution to the electrochemical
      surface potential, (2) a re-analysis is performed of the existing bulk and
      cluster ion hydration data, and (3) extensive computational modeling is conducted
      to examine the size dependence of hydration enthalpy differences for the NaF ion
      pair between the small cluster and the converged bulk limits. The computational
      studies include classical polarizable models and high-level quantum chemical
      methods. The new theoretical analysis of existing experimental data and the
      combined classical/quantum modeling lead to results consistent with our
      previously derived proton hydration quantities. 

PMID- 25399178
TI  - Polarizability anisotropy relaxation in nanoconfinement: molecular simulation
      study of water in cylindrical silica pores.
AB  - We report the results of a molecular simulation study of polarizability
      anisotropy relaxation for water confined in approximately cylindrical silica
      pores, with diameters in the range from 20 to 40 A. In our calculations, we use a
      polarizability model that includes molecular and interaction-induced components.
      In agreement with optical Kerr effect experimental data, we find strong
      confinement effects on the relaxation rate of water polarizability anisotropy.
      Given that water molecular polarizability anisotropy is small, much of the
      intensity of the polarizability anisotropy response comes from the interaction
      induced component. However, we find that, at longer times, the relaxation
      properties of this component strongly resemble those of collective reorientation,
      the mechanism by which the molecular polarizability anisotropy relaxes. We also
      find that the relevant collective orientational relaxation differs considerably
      from single molecule reorientation and that this difference varies with the
      extent of confinement. Our investigation of the effects of axial-radial pore
      anisotropy indicates that these effects play a minor role in water polarizability
      anisotropy relaxation in this pore diameter range. 

PMID- 25399179
TI  - Molecular interactions with ice: molecular embedding, adsorption, detection, and
      release.
AB  - The interaction of atomic and molecular species with water and ice is of
      fundamental importance for chemistry. In a previous series of publications, we
      demonstrated that translational energy activates the embedding of Xe and Kr atoms
      in the near surface region of ice surfaces. In this paper, we show that inert
      molecular species may be absorbed in a similar fashion. We also revisit Xe
      embedding, and further probe the nature of the absorption into the selvedge. CF4
      molecules with high translational energies (>=3 eV) were observed to embed in
      amorphous solid water. Just as with Xe, the initial adsorption rate is strongly
      activated by translational energy, but the CF4 embedding probability is much less
      than for Xe. In addition, a larger molecule, SF6, did not embed at the same
      translational energies that both CF4 and Xe embedded. The embedding rate for a
      given energy thus goes in the order Xe > CF4 > SF6. We do not have as much data
      for Kr, but it appears to have a rate that is between that of Xe and CF4.
      Tentatively, this order suggests that for Xe and CF4, which have similar van der
      Waals radii, the momentum is the key factor in determining whether the incident
      atom or molecule can penetrate deeply enough below the surface to embed. The more
      massive SF6 molecule also has a larger van der Waals radius, which appears to
      prevent it from stably embedding in the selvedge. We also determined that the
      maximum depth of embedding is less than the equivalent of four layers of
      hexagonal ice, while some of the atoms just below the ice surface can escape
      before ice desorption begins. These results show that energetic ballistic
      embedding in ice is a general phenomenon, and represents a significant new
      channel by which incident species can be trapped under conditions where they
      would otherwise not be bound stably as surface adsorbates. These findings have
      implications for many fields including environmental science, trace gas
      collection and release, and the chemical composition of astrophysical icy bodies
      in space. 

PMID- 25399180
TI  - Turning things downside up: adsorbate induced water flipping on Pt(111).
AB  - We have examined the adsorption of the weakly bound species N2, O2, CO, and Kr on
      the (?37*?37)R25.3 degrees  water monolayer on Pt(111) using a combination of
      molecular beam dosing, infrared reflection absorption spectroscopy, and
      temperature programmed desorption. In contrast to multilayer crystalline ice, the
      adsorbate-free water monolayer is characterized by a lack of dangling OH bonds
      protruding into the vacuum (H-up). Instead, the non-hydrogen-bonded OH groups are
      oriented downward (H-down) to maximize their interaction with the underlying
      Pt(111) substrate. Adsorption of Kr and O2 have little effect on the structure
      and vibrational spectrum of the "?37" water monolayer while adsorption of both
      N2, and CO are effective in "flipping" H-down water molecules into an H-up
      configuration. This "flipping" occurs readily upon adsorption at temperatures as
      low as 20 K and the water monolayer transforms back to the H-down, "?37"
      structure upon adsorbate desorption above 35 K, indicating small energy
      differences and barriers between the H-down and H-up configurations. The results
      suggest that converting water in the first layer from H-down to H-up is mediated
      by the electrostatic interactions between the water and the adsorbates.

PMID- 25399181
TI  - Temperature dependence of local solubility of hydrophobic molecules in the liquid
      vapor interface of water.
AB  - One important aspect of the hydrophobic effect is that solubility of small,
      nonpolar molecules in liquid water decreases with increasing temperature. We
      investigate here how the characteristic temperature dependence in liquid water
      persists or changes in the vicinity of the liquid-vapor interface. From the
      molecular dynamics simulation and the test-particle insertion method, the local
      solubility Sigma of methane in the liquid-vapor interface of water as well as
      Sigma of nonpolar solutes in the interface of simple liquids are calculated as a
      function of the distance z from the interface. We then examine the temperature
      dependence of Sigma under two conditions: variation of Sigma at fixed position z
      and that at fixed local solvent density around the solute molecule. It is found
      that the temperature dependence of Sigma at fixed z depends on the position z and
      the system, whereas Sigma at fixed local density decreases with increasing
      temperature for all the model solutions at any fixed density between vapor and
      liquid phases. The monotonic decrease of Sigma under the fixed-density condition
      in the liquid-vapor interface is in accord with what we know for the solubility
      of nonpolar molecules in bulk liquid water under the fixed-volume condition but
      it is much robust since the solvent density to be fixed can be anything between
      the coexisting vapor and liquid phases. A unique feature found in the water
      interface is that there is a minimum in the local solubility profile Sigma(z) on
      the liquid side of the interface. We find that with decreasing temperature the
      minimum of Sigma grows and at the same time the first peak in the oscillatory
      density profile of water develops. It is likely that the minimum of Sigma is due
      to the layering structure of the free interface of water. 

PMID- 25399182
TI  - Wetting transparency of graphene in water.
AB  - Measurements of contact angle on graphene sheets show a notable dependence on the
      nature of the underlying substrate, a phenomenon termed wetting transparency. Our
      molecular modeling studies reveal analogous transparency in case of submerged
      graphene fragments in water. A combined effect of attractive dispersion forces,
      angle correlations between aqueous dipoles, and repulsion due to the hydrogen
      bond-induced orientation bias in polarized hydration layers acting across
      graphene sheet, enhances apparent adhesion of water to graphene. We show wetting
      free energy of a fully wetted graphene platelet to be about 8 mNm(-1) lower than
      for graphene wetted only on one side, which gives close to 10 degrees  reduction
      in contact angle. This difference has potential implications for predictions of
      water absorption vs. desorption, phase behavior of water in aqueous
      nanoconfinements, solvent-induced interactions among graphitic nanoparticle and
      concomitant stability in aqueous dispersions, and can influence permeability of
      porous materials such as carbon nanotubes by water and aqueous solutions. 

PMID- 25399183
TI  - Simulations of water transport through carbon nanotubes: how different water
      models influence the conduction rate.
AB  - The conduction rate of water through (8,8) and (9,9) carbon nanotubes at 300 K
      and a pressure difference of 220 MPa is investigated using molecular dynamics
      simulations. The TIP3P, SPC/E, and TIP4P/2005 water models are considered. The
      pressure-driven flow rate is found to be strongly model dependent for both
      nanotubes. The fastest model (TIP3P) has a flow rate that is approximately five
      times faster than the slowest (TIP4P/2005). It is shown that the flow rate is
      significantly influenced by the structure taken on by the water molecules
      confined in the nanotube channels. The slower models, TIP4P/2005 and SPC/E, tend
      to favor stacked ring arrangements, with the molecules of a ring moving together
      through the nanotube, in what we term a "cluster-by-cluster" conduction mode.
      Confined TIP3P water has a much weaker tendency to form ring structures, and
      those that do form are fragile and break apart under flow conditions. This
      creates a much faster "diffusive" conduction mode where the water molecules
      mainly move through the tube as individual particles, rather than as components
      of a larger cluster. Our results demonstrate that water models developed to
      describe the properties of bulk water can behave very differently in confined
      situations. 

PMID- 25399184
TI  - The molecular structure of the interface between water and a hydrophobic
      substrate is liquid-vapor like.
AB  - With molecular simulation for water and a tunable hydrophobic substrate, we apply
      the instantaneous interface construction [A. P. Willard and D. Chandler,
      "Instantaneous liquid interfaces," J. Phys. Chem. B 114, 1954-1958 (2010)] to
      examine the similarity between a water-vapor interface and a water-hydrophobic
      surface interface. We show that attractive interactions between a hydrophobic
      surface and water affect capillary wave fluctuations of the instantaneous liquid
      interface, but these attractive interactions have essentially no effect on the
      intrinsic interface. The intrinsic interface refers to molecular structure in
      terms of distances from the instantaneous interface. Further, the intrinsic
      interface of liquid water and a hydrophobic substrate differs little from that of
      water and its vapor. The same is not true, we show, for an interface between
      water and a hydrophilic substrate. In that case, strong directional substrate
      water interactions disrupt the liquid-vapor-like interfacial hydrogen bonding
      network. 

PMID- 25399185
TI  - Clusters, molecular layers, and 3D crystals of water on Ni(111).
AB  - We examined the growth and stability of ice layers on Ni(111) up to ~7 molecular
      layers (ML) thick using scanning tunneling microscopy. At low coverage, films
      were comprised of ~1 nm wide two-dimensional (2D) clusters. Only above ~0.5 ML
      did patches of continuous 2D layers emerge, coexisting with the clusters until
      the first ML was complete. The structure of the continuous layer is clearly
      different from that of the 2D clusters. Subsequently, a second molecular layer
      grew on top of the first. 3D crystallites started to form only after this 2nd ML
      was complete. 2D clusters re-appeared when thicker films were partially
      evaporated, implying that these clusters represent the equilibrium configuration
      at low coverage. Binding energies and image simulations computed with density
      functional theory suggest that the 2D clusters are partially dissociated and
      surrounded by H adatoms. The complete 2D layer contains only intact water
      molecules because of the lack of favorable binding sites for H atoms. We propose
      molecular structures for the 2D layer that are composed of the same pentagon
      heptagon binding motif and water density observed on Pt(111). The similarity of
      the water structures on Pt and Ni suggests a general prescription for generating
      low-energy configurations on close-packed metal substrates. 

PMID- 25399186
TI  - Insights into hydrogen bonding via ice interfaces and isolated water.
AB  - Water in a confined environment has a combination of fewer available
      configurations and restricted mobility. Both affect the spectroscopic signature.
      In this work, the spectroscopic signature of water in confined environments is
      discussed in the context of competing models for condensed water: (1) as a system
      of intramolecular coupled molecules or (2) as a network with intermolecular
      dipole-dipole coupled O-H stretches. Two distinct environments are used: the
      confined asymmetric environment at the ice surface and the near-isolated
      environment of water in an infrared transparent matrix. Both the spectroscopy and
      the environment are described followed by a perspective discussion of
      implications for the two competing models. Despite being a small molecule, water
      is relatively complex; perhaps not surprisingly the results support a model that
      blends inter- and intramolecular coupling. The frequency, and therefore the
      hydrogen-bond strength, appears to be a function of donor-acceptor interaction
      and of longer-range dipole-dipole alignment in the hydrogen-bonded network. The O
      H dipole direction depends on the local environment and reflects intramolecular O
      H stretch coupling. 

PMID- 25399187
TI  - Effect of a potential softness on the solid-liquid transition in a two
      dimensional core-softened potential system.
AB  - In the present paper, using a molecular dynamics simulation, we study a nature of
      melting of a two-dimensional (2D) system of classical particles interacting
      through a purely repulsive isotropic core-softened potential which is used for
      the qualitative description of the anomalous behavior of water and some other
      liquids. We show that the melting scenario drastically depends on the potential
      softness and changes with increasing the width of the smooth repulsive shoulder.
      While at small width of the repulsive shoulder the melting transition exhibits
      what appears to be weakly first-order behavior, at larger values of the width a
      reentrant-melting transition occurs upon compression for not too high pressures,
      and in the low density part of the 2D phase diagram melting is a continuous two
      stage transition, with an intermediate hexatic phase in accordance with the
      Kosterlitz-Thouless-Halperin-Nelson-Young scenario. On the other hand, at high
      density part of the phase diagram one first-order transition takes place. These
      results may be useful for the qualitative understanding the behavior of water
      confined between two hydrophobic plates. 

PMID- 25399188
TI  - Origins of the non-exponential reorientation dynamics of nanoconfined water.
AB  - The dynamics of water are dramatically modified upon confinement in nanoscale
      hydrophilic silica pores. In particular, the OH reorientation dynamics of the
      interfacial water are non-exponential and dramatically slowed relative to the
      bulk liquid. A detailed analysis of molecular dynamics simulations is carried out
      to elucidate the microscopic origins of this behavior. The results are analyzed
      in the context of the extended jump model for water that describes the
      reorientation as a combination of hydrogen-bond exchanges, or jumps, and rotation
      of intact hydrogen bonds, with the former representing the dominant contribution.
      Within this model, the roles of surface and dynamical heterogeneities are
      considered by spatially resolving the hydrogen-bond jump dynamics into individual
      sites on the silica pore surface. For each site the dynamics is nearly mono
      exponential, indicating that dynamical heterogeneity is at most a minor
      influence, while the distribution of these individual site jump times is broad.
      The non-exponential dynamics can also not be attributed to enthalpic
      contributions to the barriers to hydrogen-bond exchanges. Two entropic effects
      related to the surface roughness are found to explain the retarded and diverse
      dynamics: those associated with the approach of a new hydrogen-bond acceptor and
      with the breaking of the initial hydrogen-bond. 

PMID- 25399189
TI  - Sum frequency and second harmonic generation from the surface of a liquid
      microjet.
AB  - The use of a liquid microjet as a possible source of interest for Second Harmonic
      Generation (SHG) and Sum Frequency Generation (SFG) spectroscopy is examined. We
      measured non-resonant SHG scattering patterns from the air/water interface of a
      microjet of pure water and observe a strong enhancement of the SHG signal for
      certain scattering angles. These enhancements can be explained by the optical
      properties and the shape of the liquid microjet. SFG experiments at the surface
      of a liquid microjet of ethanol in air show that it is also possible to measure
      the coherent vibrational SFG spectrum of the ethanol/air interface in this way.
      Our findings are useful for future far-UV or X-ray based nonlinear optical
      surface experiments on liquid jets. In addition, combined X-ray photoelectron
      spectroscopy and SHG/SFG measurements are feasible, which will be very useful in
      improving our understanding of the molecular foundations of electrostatic and
      chemical surface properties and phenomena. 

PMID- 25399190
TI  - Investigating the solid-liquid phase transition of water nanofilms using the
      generalized replica exchange method.
AB  - The generalized Replica Exchange Method (gREM) was applied to study a solid
      liquid phase transition in a nanoconfined bilayer water system using the
      monatomic water (mW) model. Exploiting optimally designed non-Boltzmann sampling
      weights with replica exchanges, gREM enables an effective sampling of
      configurations that are metastable or unstable in the canonical ensemble via
      successive unimodal energy distributions across phase transition regions, often
      characterized by S-loop or backbending in the statistical temperature. Extensive
      gREM simulations combined with Statistical Temperature Weighted Histogram
      Analysis Method (ST-WHAM) for nanoconfined mW water at various densities provide
      a comprehensive characterization of diverse thermodynamic and structural
      properties intrinsic to phase transitions. Graph representation of minimized
      structures of bilayer water systems determined by the basin-hopping global
      optimization revealed heterogeneous ice structures composed of pentagons,
      hexagons, and heptagons, consistent with an increasingly ordered solid phase with
      decreasing density. Apparent crossover from a first-order solid-liquid transition
      to a continuous one in nanoconfined mW water with increasing density of the
      system was observed in terms of a diminishing S-loop in the statistical
      temperature, smooth variation of internal energies and heat capacities, and a
      characteristic variation of lateral radial distribution functions, and transverse
      density profiles across transition regions. 

PMID- 25399191
TI  - Large permeabilities of hourglass nanopores: from hydrodynamics to single file
      transport.
AB  - In fluid transport across nanopores, there is a fundamental dissipation that
      arises from the connection between the pore and the macroscopic reservoirs. This
      entrance effect can hinder the whole transport in certain situations, for short
      pores and/or highly slipping channels. In this paper, we explore the hydrodynamic
      permeability of hourglass shape nanopores using molecular dynamics (MD)
      simulations, with the central pore size ranging from several nanometers down to a
      few Angstroms. Surprisingly, we find a very good agreement between MD results and
      continuum hydrodynamic predictions, even for the smallest systems undergoing
      single file transport of water. An optimum of permeability is found for an
      opening angle around 5 degrees , in agreement with continuum predictions,
      yielding a permeability five times larger than for a straight nanotube. Moreover,
      we find that the permeability of hourglass shape nanopores is even larger than
      single nanopores pierced in a molecular thin graphene sheet. This suggests that
      designing the geometry of nanopores may help considerably increasing the
      macroscopic permeability of membranes. 

PMID- 25399192
TI  - Interfacial water in the vicinity of a positively charged interface studied by
      steady-state and time-resolved heterodyne-detected vibrational sum frequency
      generation.
AB  - To investigate the properties of water in the close vicinity of a positively
      charged surfactant/water interface, steady-state and femtosecond time-resolved
      interfacial vibrational spectra were measured in the presence of excess alkali
      halide salts. The steady-state Imchi((2)) spectra show a drastic intensity
      decrease with excess salts, indicating that the thickness of the probed water
      layer is substantially reduced. Fluoride salts do not noticeably affect spectral
      features in the OH stretch region whereas the chloride and bromide salts induce
      significant blue shifts of the OH stretch frequency. Femtosecond time-resolved
      DeltaImchi((2)) spectra obtained with fluoride salts exhibit a very broad bleach
      even at 0 fs as observed without excess salts, while chloride and bromide salts
      give rise to a narrow spectral hole burning. These results indicate that the
      excess chloride and bromide ions strongly interact with interfacial water in the
      vicinity of the charged interface and it suppresses intramolecular coupling
      (i.e., Fermi resonance) that causes spectral broadening. 

PMID- 25399193
TI  - Transport behavior of water molecules through two-dimensional nanopores.
AB  - Water transport through a two-dimensional nanoporous membrane has attracted
      increasing attention in recent years thanks to great demands in water
      purification and desalination applications. However, few studies have been
      reported on the microscopic mechanisms of water transport through structured
      nanopores, especially at the atomistic scale. Here we investigate the
      microstructure of water flow through two-dimensional model graphene membrane
      containing a variety of nanopores of different size by using molecular dynamics
      simulations. Our results clearly indicate that the continuum flow transits to
      discrete molecular flow patterns with decreasing pore sizes. While for pores with
      a diameter >=15 A water flux exhibits a linear dependence on the pore area, a
      nonlinear relationship between water flux and pore area has been identified for
      smaller pores. We attribute this deviation from linear behavior to the presence
      of discrete water flow, which is strongly influenced by the water-membrane
      interaction and hydrogen bonding between water molecules. 

PMID- 25399194
TI  - Homogeneous ice nucleation evaluated for several water models.
AB  - In this work, we evaluate by means of computer simulations the rate for ice
      homogeneous nucleation for several water models such as TIP4P,
      TIP4P/2005,TIP4P/ICE, and mW (following the same procedure as in Sanz et al. [J.
      Am. Chem. Soc. 135, 15008 (2013)]) in a broad temperature range. We estimate the
      ice-liquid interfacial free-energy, and conclude that for all water models gamma
      decreases as the temperature decreases. Extrapolating our results to the melting
      temperature, we obtain a value of the interfacial free-energy between 25 and 32
      mN/m in reasonable agreement with the reported experimental values. Moreover, we
      observe that the values of gamma depend on the chosen water model and this is a
      key factor when numerically evaluating nucleation rates, given that the kinetic
      prefactor is quite similar for all water models with the exception of the mW (due
      to the absence of hydrogens). Somewhat surprisingly the estimates of the
      nucleation rates found in this work for TIP4P/2005 are slightly higher than those
      of the mW model, even though the former has explicit hydrogens. Our results
      suggest that it may be possible to observe in computer simulations spontaneous
      crystallization of TIP4P/2005 at about 60 K below the melting point. 

PMID- 25399195
TI  - Water on BN doped benzene: a hard test for exchange-correlation functionals and
      the impact of exact exchange on weak binding.
AB  - Density functional theory (DFT) studies of weakly interacting complexes have
      recently focused on the importance of van der Waals dispersion forces, whereas
      the role of exchange has received far less attention. Here, by exploiting the
      subtle binding between water and a boron and nitrogen doped benzene derivative
      (1,2-azaborine) we show how exact exchange can alter the binding conformation
      within a complex. Benchmark values have been calculated for three orientations of
      the water monomer on 1,2-azaborine from explicitly correlated quantum chemical
      methods, and we have also used diffusion quantum Monte Carlo. For a host of
      popular DFT exchange-correlation functionals we show that the lack of exact
      exchange leads to the wrong lowest energy orientation of water on 1,2-azaborine.
      As such, we suggest that a high proportion of exact exchange and the associated
      improvement in the electronic structure could be needed for the accurate
      prediction of physisorption sites on doped surfaces and in complex organic
      molecules. Meanwhile to predict correct absolute interaction energies an accurate
      description of exchange needs to be augmented by dispersion inclusive
      functionals, and certain non-local van der Waals functionals (optB88- and optB86b
      vdW) perform very well for absolute interaction energies. Through a comparison
      with water on benzene and borazine (B3N3H6) we show that these results could have
      implications for the interaction of water with doped graphene surfaces, and
      suggest a possible way of tuning the interaction energy. 

PMID- 25399196
TI  - The role of material flexibility on the drying transition of water between
      hydrophobic objects: a thermodynamic analysis.
AB  - Liquid water confined between hydrophobic objects of sufficient size becomes
      metastable with respect to its vapor at separations smaller than a critical
      drying distance. Macroscopic thermodynamic arguments predicting this distance
      have been restricted to the limit of perfectly rigid confining materials.
      However, no material is perfectly rigid and it is of interest to account for this
      fact in the thermodynamic analysis. We present a theory that combines the current
      macroscopic theory with the thermodynamics of elasticity to derive an expression
      for the critical drying distance for liquids confined between flexible materials.
      The resulting expression is the sum of the well-known drying distance for
      perfectly rigid confining materials and a new term that accounts for flexibility.
      Thermodynamic arguments show that this new term is necessarily positive, meaning
      that flexibility increases the critical drying distance. To study the expected
      magnitude and scaling behavior of the flexible term, we consider the specific
      case of water and present an example of drying between thin square elastic plates
      that are simply supported along two opposite edges and free at the remaining two.
      We find that the flexible term can be the same order of magnitude or greater than
      the rigid solution for materials of biological interest at ambient conditions. In
      addition, we find that when the rigid solution scales with the characteristic
      size of the immersed objects, the flexible term is independent of size and vice
      versa. Thus, the scaling behavior of the overall drying distance will depend on
      the relative weights of the rigid and flexible contributions. 

PMID- 25399197
TI  - Water transport through functionalized nanotubes with tunable hydrophobicity.
AB  - Molecular dynamics simulations are used to study the occupancy and flow of water
      through nanotubes comprised of hydrophobic and hydrophilic atoms, which are
      arranged on a honeycomb lattice to mimic functionalized carbon nanotubes (CNTs).
      We consider single-file motion of TIP3P water through narrow channels of (6,6)
      CNTs with varying fractions (f) of hydrophilic atoms. Various arrangements of
      hydrophilic atoms are used to create heterogeneous nanotubes with separate
      hydrophobic/hydrophilic domains along the tube as well as random mixtures of the
      two types of atoms. The water occupancy inside the nanotube channel is found to
      vary nonlinearly as a function of f, and a small fraction of hydrophilic atoms (f
      ~ 0.4) are sufficient to induce spontaneous and continuous filling of the
      nanotube. Interestingly, the average number of water molecules inside the channel
      and water flux through the nanotube are less sensitive to the specific
      arrangement of hydrophilic atoms than to the fraction, f. Two different regimes
      are observed for the water flux dependence on f - an approximately linear
      increase in flux as a function of f for f < 0.4, and almost no change in flux for
      higher f values, similar to the change in water occupancy. We are able to define
      an effective interaction strength between nanotube atoms and water's oxygen,
      based on a linear combination of interaction strengths between hydrophobic and
      hydrophilic nanotube atoms and water, that can quantitatively capture the
      observed behavior. 

PMID- 25399198
TI  - Phase separation during freezing upon warming of aqueous solutions.
AB  - Using differential scanning calorimetry, we show that the addition of solute(s)
      to emulsified water lowers the freezing temperature to <231 K, the homogeneous
      nucleation temperature of pure bulk water, or even completely suppresses
      freezing. In the latter case, freezing upon warming occurs above T(X) ~ 150 K and
      leads to a phase separation into pure ice and a freeze-concentrated solution
      (FCS) which crystallizes upon further warming. We also show that emulsified 20
      21.5 wt. % HCl solutions and the FCS of HCl/H2O solutions transform to glass at
      T(g) ~ 127-128 K, i.e., lower than T(g) ~ 136 K of water. We suggest that water
      nanodrops adsorbed on fumed silica resemble bulk water more than water confined
      in nanoscaled confinement and also more than nanoscaled water domains in aqueous
      solution.

PMID- 25399199
TI  - A matter of quantum voltages.
AB  - Voltages inside matter are relevant to crystallization, materials science,
      biology, catalysis, and aqueous chemistry. The variation of voltages in matter
      can be measured by experiment, however, modern supercomputers allow the
      calculation of accurate quantum voltages with spatial resolutions of bulk systems
      well beyond what can currently be measured provided a sufficient level of theory
      is employed. Of particular interest is the Mean Inner Potential (V(o))--the
      spatial average of these quantum voltages referenced to the vacuum. Here we
      establish a protocol to reliably evaluate V(o) from quantum calculations.
      Voltages are very sensitive to the distribution of electrons and provide metrics
      to understand interactions in condensed phases. In the present study, we find
      excellent agreement with measurements of V(o) for vitrified water and salt
      crystals and demonstrate the impact of covalent and ionic bonding as well as
      intermolecular/atomic interactions. Certain aspects in this regard are
      highlighted making use of simple model systems/approximations. Furthermore, we
      predict V(o) as well as the fluctuations of these voltages in aqueous NaCl
      electrolytes and characterize the changes in their behavior as the resolution
      increases below the size of atoms.

PMID- 25399200
TI  - Structure and dynamics of water in nanoscopic spheres and tubes.
AB  - We study the reorientation dynamics of liquid water confined in nanometer-sized
      reverse micelles of spherical and cylindrical shape. The size and shape of the
      micelles are characterized in detail using small-angle x-ray scattering, and the
      reorientation dynamics of the water within the micelles is investigated using GHz
      dielectric relaxation spectroscopy and polarization-resolved infrared pump-probe
      spectroscopy on the OD-stretch mode of dilute HDO:H2O mixtures. We find that the
      GHz dielectric response of both the spherical and cylindrical reverse micelles
      can be well described as a sum of contributions from the surfactant, the water at
      the inner surface of the reversed micelles, and the water in the core of the
      micelles. The Debye relaxation time of the core water increases from the bulk
      value tau(H2O) of 8.2 +/- 0.1 ps for the largest reverse micelles with a radius
      of 3.2 nm to 16.0 +/- 0.4 ps for the smallest micelles with a radius of 0.7 nm.
      For the nano-spheres the dielectric response of the water is approximately ~6
      times smaller than expected from the water volume fraction and the bulk
      dielectric relaxation of water. We find that the dielectric response of nano
      spheres is more attenuated than that of nano-tubes of identical composition
      (water-surfactant ratio), whereas the reorientation dynamics of the water
      hydroxyl groups is identical for the two geometries. We attribute the attenuation
      of the dielectric response compared to bulk water to a local anti-parallel
      ordering of the molecular dipole moments. The difference in attenuation between
      nano-spheres and nano-cylinders indicates that the anti-parallel ordering of the
      water dipoles is more pronounced upon spherical than upon cylindrical
      nanoconfinement.

PMID- 25399201
TI  - End--users' perception of quality of care of children attending children's
      outpatients clinics of University of Nigeria Teaching Hospital Ituku--Ozalla
      Enugu.
AB  - BACKGROUND: Knowledge of the specific details of end-users actual experiences
      with health system helps to identify areas for improvement in ways that
      standardized satisfaction measures are less able to provide in order to save
      lives, uphold public confidence and trust in healthcare delivery. The aim of the
      study was to assess the end-users' perception of the quality of clinical services
      rendered to children attending paediatric out-patient clinics of University of
      Nigeria Teaching Hospital, Ituku - Ozalla, Enugu. METHODS: A cross sectional
      descriptive study was undertaken using exit point interviewer administered pre
      tested/semi-structured questionnaire.Assessment of perception of quality of care
      was undertaken in three service areas; waiting time, attitude of staff and
      comfort of the waiting hall. Data was analyzed using SPSS 16.0 and presented as
      percentages. Chi-square was used to compare means (p < 0.05). RESULTS: A total of
      367 respondents were interviewed. Over 50% of them were generally satisfied with
      overall quality of care. 329 (89.6%) were very satisfied with quality of doctors'
      services, while the least satisfaction was with the quality of medical records
      services 139 (37.9%). Majority of the respondents 197 (53.7%) spent between 3-6
      hours for each clinic visit and most of the waiting time spent was in the medical
      records and consultation. CONCLUSION: The care--givers perception of the general
      quality of care was adjudged high. However, overall waiting time was perceived to
      be unsatisfactory.Efforts should be made to reduce the time spent by clients
      while accessing care in the facility.

PMID- 25399204
TI  - Trends in birthweight among four tribal communities in rural Tamil Nadu, India.

PMID- 25399203
TI  - Autoimmune pancreatitis complicated with inflammatory bowel disease and
      comparative study of type 1 and type 2 autoimmune pancreatitis.
AB  - BACKGROUND: Two types of autoimmune pancreatitis (AIP) have been reported,
      lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric chronic
      pancreatitis (IDCP), which are now recognized as type 1 and type 2 AIP,
      respectively. Since the clinical features of type 2 AIP have not been fully
      elucidated and this condition is frequently accompanied by inflammatory bowel
      disease (IBD), we performed a nationwide survey of patients with AIP complicated
      with IBD to precisely characterize this disease entity. METHODS: We collected 138
      cases of pancreatitis with complicating IBD from affiliated institutes
      specializing in AIP or IBD, and comparative study between the IDCP groups and
      type 1 AIP was performed. RESULTS: Histological examination revealed 15 AIP cases
      to be IDCP of institutional diagnosis, among which 11 cases were upgraded to IDCP
      of central diagnosis by an expert pathologist. The IDCP group exhibited younger
      onset age, no gender bias, frequent abdominal pain, and normal IgG4 value,
      similar to those of type 2 AIP reported previously. We also witnessed a lower
      prevalence of jaundice in type 2 AIP than in type 1 AIP that corresponded to
      imaging findings of less frequent pancreatic head swelling and scarce bile duct
      stenosis. CONCLUSIONS: A characteristic feature of type 2 AIP compared with type
      1 AIP is a low frequency of obstructive jaundice that is related to rare lower
      bile duct stricture due to lower prevalence of pancreatic head swelling. Contrary
      to type 1 AIP, lower bile duct stricture in this condition has no apparent
      relation to sclerosing cholangitis.

PMID- 25399205
TI  - Intraspecies comparison of Streptomyces pratensis genomes reveals high levels of
      recombination and gene conservation between strains of disparate geographic
      origin.
AB  - BACKGROUND: Streptomyces are widespread bacteria that contribute to the
      terrestrial carbon cycle and produce the majority of clinically useful
      antibiotics. While interspecific genomic diversity has been investigated among
      Streptomyces, information is lacking on intraspecific genomic diversity.
      Streptomyces pratensis has high rates of homologous recombination but the impact
      of such gene exchange on genome evolution and the evolution of natural product
      gene clusters remains uncharacterized. RESULTS: We report draft genome sequences
      of four S. pratensis strains and compare to the complete genome of Streptomyces
      flavogriseus IAF-45-CD (=ATCC 33331), a strain recently reclassified to S.
      pratensis. Despite disparate geographic origins, the genomes are highly similar
      with 85.9% of genes present in the core genome and conservation of all natural
      product gene clusters. Natural products include a novel combination of carbapenem
      and beta-lactamase inhibitor gene clusters. While high intraspecies recombination
      rates abolish the phylogenetic signal across the genome, intraspecies
      recombination is suppressed in two genomic regions. The first region is centered
      on an insertion/deletion polymorphism and the second on a hybrid NRPS-PKS gene.
      Finally, two gene families accounted for over 25% of the divergent genes in the
      core genome. The first includes homologs of bldB (required for spore development
      and antibiotic production) while the second includes homologs of an
      uncharacterized protein with a helix-turn-helix motif (hpb). Genes from these
      families co-occur with fifteen pairs spread across the genome. These genes have
      evidence for co-evolution of co-localized pairs, supporting previous assertions
      that these genes may function akin to a toxin-antitoxin system. CONCLUSIONS: S.
      pratensis genomes are highly similar with exceptional levels of recombination
      which erase phylogenetic signal among strains of the species. This species has a
      large core genome and variable terminal regions that are smaller than those found
      in interspecies comparisons. There is no geographic differentiation between these
      strains, but there is evidence for local linkage disequilibrium affecting two
      genomic regions. We have also shown further observational evidence that the
      DUF397-HTH (bldB and hpb) are a novel toxin-antitoxin pair.

PMID- 25399207
TI  - Comparison between total laparoscopy and laparoscopy-assisted distal gastrectomy
      for gastric cancer. A meta-analysis based on Japanese and Korean articles.
AB  - OBJECTIVES: To assess the safety and feasibility of total laparoscopy distal
      gastrectomy (TLDG). METHODS: This meta-analysis was conducted between April and
      July 2013 in Sichuan Cancer Hospital, Chengdu, China. We searched PubMed, EMBASE
      and China Knowledge Resource Integrated Database updated until May 2013. Eight
      retrospective studies and one prospective study involving 2,046 total patients
      were included. RESULTS: The results showed that TLDG was associated with lower
      blood loss (mean difference=-22.39, p=0.04). and a greater number of harvested
      lymph nodes (mean difference=2.74, p=0.02). There was no significant difference
      between the 2 groups in operation time, time to first flatus, length of
      postoperative hospital stay, and postoperative complications. CONCLUSION:
      Compared with laparoscopy-assisted distal gastrectomy, TLDG resulted in reduced
      blood loss, and a greater number of harvested lymph nodes. Total laparoscopy
      distal gastrectomy is safe and feasible for gastric cancer. 

PMID- 25399206
TI  - The current status of beta blockers' use in the management of hypertension.
AB  - The invention of beta (beta)-blockers culminated in a new era in the treatment of
      cardiovascular diseases (CD), and changed the course of pharmacology research for
      years to come. Since the introduction of propranolol into clinical practice in
      1964, beta-blockers enjoyed a special place in the clinicians' armamentarium
      against CDs, especially for patients with ischemic heart diseases, and are still
      one of the most extensively used therapeutic drugs in both cardiac and non
      cardiac ailments. Current uses of beta-blockers in CDs include ischemic heart
      diseases, hypertension, cardiac arrhythmias, and heart failure. Other substantial
      non-cardiac uses include glaucoma, migraine, situational anxiety, benign
      essential tremors, and cardiac symptoms of thyrotoxicosis. This review covers
      some of the evolutionary changes of clinical uses of beta-blockers, the rationale
      for their use, some recent controversies surrounding their use for treatment of
      hypertension, and advantages of newer additions to the group.  

PMID- 25399208
TI  - Distinct outcomes in patients with different molecular subtypes of inflammatory
      breast cancer.
AB  - OBJECTIVES: To determine the outcome of patients with luminal A, luminal B, human
      epidermal growth factor receptor-2 (HER-2) positive, and triple negative
      molecular subtypes of inflammatory breast cancer (IBC) using a retrospective
      analysis. METHODS: This study was conducted between February 2004 and February
      2010 in 3 different hospitals in China. The clinical outcomes, pathological
      features, and treatment strategies were analyzed in 67 cases of IBC without
      distant metastases. A chi-square test and one-way ANOVA were used to assess
      outcomes between different subtypes. Overall survival (OS) was analyzed using the
      Kaplan-Meier method and multivariate analysis was conducted using the Cox
      regression model. RESULTS: The 2-year OS rate was 55% for the entire cohort.
      Median OS time among patients with luminal A was 35 months, luminal B was 30
      months, HER-2 positive was 24 months, and triple negative subtypes was 20 months,
      and were significantly different from each other (p=0.001). Using multivariate
      analysis, luminal A had 76% (p=0.037), luminal B had 54% (p=0.048), and HER-2
      positive subtypes had 47% (p=0.032) decreased risk of death compared with the
      triple negative subtype.  Furthermore, elevated Ki-67 labeling was associated
      with increased risk of death, while the surgical treatment significantly improved
      patient survival. CONCLUSION: Breast cancer subtypes are associated with distinct
      outcomes in IBC patients. Patients that presented with triple negative IBC had
      poorer outcome than luminal A, luminal B, and HER-2 subtypes. These results
      indicate that IBC is a heterogeneous disease similar to the conventional breast
      cancer. 

PMID- 25399209
TI  - Histopathological and immune alterations in autopsied kidneys.
AB  - OBJECTIVES: To collect data on all detectable histologic and immune alterations
      from the kidneys of 55 autopsy cases. METHODS: This prospective study was carried
      out at the Department of Pathology, Medical Faculty, Trakya University, Edirne,
      Turkey. Fifty-five cases were subjected to the study among 248 autopsies that
      were performed in 2011 and 2012. All kidney samples were evaluated under a light
      microscope and fresh tissue samples were used for immunofluorescence microscopy.
      Immunohistochemically kappa (kappa) and lambda (lambda) antibodies were applied
      to the tissue sections. The glomerular, tubulo-interstitial, and vascular
      alterations, as well as immune depositions were noted. RESULTS: The microscopic
      morphology was close to normal histology in only 23 cases, and 23 cases had
      glomerular alterations. Nineteen cases had at least one immune deposition. There
      was immunoglobulin A deposition in 13 cases, and 9 cases showed positivity for
      both kappa and lambda immunohistochemically, and there was no clonal positivity.
      CONCLUSION: The most striking outcome of our study is the high rate of immune
      depositions. There was also a significant number of glomerular and non-glomerular
      renal alterations. 

PMID- 25399210
TI  - Does combined peroxisome proliferator-activated receptors-agonist and pravastatin
      therapy attenuate the onset of diabetes-induced experimental nephropathy?
AB  - OBJECTIVES: To investigate the combined effects of rosiglitazone and pravastatin
      on renal functions in early streptozotocin induced diabetic nephropathy (DN).
      METHODS: This study was carried out at King Khalid University Hospital Animal
      House, Riyadh, Saudi Arabia from August 2013 to February 2014. Fifty male Wistar
      rats were assigned to normal control rats and diabetic rats that received saline,
      rosiglitazone, pravastatin, or rosiglitazone+pravastatin for 2 months. Their
      weight range was 230-250 gm, and age range was from 18-20 weeks. At the end of
      experiment, creatinine clearance, and urinary albumin to creatinine ratio (ACR)
      were measured. Blood samples were analyzed for transferrin, glycosylated
      hemoglobin (HbA1c), lipid profile, tumor necrosis factor-alpha (TNF-alpha),
      intercellular adhesion molecule-1 (ICAM-1), and lipid peroxide. RESULTS:
      Rosiglitazone treatment increased creatinine clearance and plasma transferrin,
      and decreased urinary ACR, HbA1c, plasma TNF-alpha, ICAM-1, and serum lipid
      peroxide levels without affecting the altered lipid profile. Pravastatin
      treatment produced similar results and normalized the lipid alteration. The
      combination of rosiglitazone and pravastatin was more effective in attenuating
      the diabetes-induced nephropathy compared with treatment with either drug alone.
      CONCLUSION: The combination strategy of rosiglitazone and pravastatin may provide
      a potential synergistic renoprotective effect against DN by improving renal
      functions and reducing indices of DN. 

PMID- 25399211
TI  - Viral etiology of respiratory infections in children in southwestern Saudi Arabia
      using multiplex reverse-transcriptase polymerase chain reaction.
AB  - OBJECTIVES: To investigate 15 respiratory viruses in children with acute
      respiratory tract infections (ARTIs) using multiplex reverse-transcriptase
      polymerase chain reaction (RT-PCR), and to analyze the clinical and
      epidemiological features of these viruses. METHODS: In a cross-sectional study,
      135 children, <=5 years of age who presented with ARTIs in Najran Maternity and
      Children Hospital, Najran, Saudi Arabia between October 2012 and July 2013 were
      included. The clinical and sociodemographic data, and the laboratory results were
      recorded using a standardized questionnaire. Two nasopharyngeal swabs were
      collected from each child: one for bacteriological examination, and the second
      for viral detection using multiplex RT-PCR. RESULTS: A single viral pathogen was
      detected in 76 patients, viral coinfections in 9, and mixed viral and bacterial
      pathogens in 15. Respiratory syncytial virus was isolated in 33 patients, human
      rhinovirus (hRV) in 22, adenovirus (AdV) in 19, human metapneumovirus in 13,
      influenza virus in 10, parainfluenza virus in 7, human corona virus (hCoV) in 4,
      and human bocavirus in one. CONCLUSION: Respiratory syncytial virus, hRV, and AdV
      were the most frequent viruses, accounting for more than two-thirds of the cases.
      Other viruses, such as MPV, hCoV NL63, and hCoV OC43, may play a role in
      pediatric ARTIs. Of significance is the potential use of multiplex RT-PCR to
      provide epidemiological and virological data for early detection of the emergence
      of novel respiratory viruses in the era of the Middle East respiratory syndrome
      coronavirus. 

PMID- 25399212
TI  - Nosocomial infections in ambulances and effectiveness of ambulance fumigation
      techniques in Saudi Arabia. Phase I study.
AB  - OBJECTIVES: To evaluate infection control and the incidence of bacterial
      pathogens in Emergency Medical Service (EMS) ambulances in Riyadh, Saudi Arabia.
      The effectiveness of fumigation techniques used for these ambulances to minimize
      the spread of infection to transported patients and pre-hospital care providers
      was also assessed. METHODS: Based on previous literature review indicating a
      higher propensity of microbial load, 3 areas within the ambulance, such as,
      stretcher handle, oxygen flow meter knob, and interior handle of the rear door
      were selected for specimen collection. Swab samples were collected both in the
      day and night shift, after the intended disinfection and cleaning (before and
      after fumigation). Micro-organisms were identified using standard procedures.
      This phase-I study was conducted at the Emergency Medical Services Department,
      Prince Sultan Bin AbdulAziz College of Emergency Medical Services, Al Malaz, King
      Saud University, Riyadh, Saudi Arabia between October and November 2013, wherein
      a total of 10 ambulances from the Saudi Red Crescent Authority in Riyadh were
      selected for inclusion in the study. RESULTS: The specimens from all 10
      ambulances showed similar results. In post disinfection and before fumigation,
      swab samples showed positive cultures that grew moderate to large quantities of
      environmental and skin flora. However, almost all organisms were susceptible to
      the fumigation technique. CONCLUSION: This study confirms the importance of
      evaluating the frequency and efficiency of various fumigation techniques as an
      ambulance is a potential reservoir for microbial transmission to patients and
      staff.

PMID- 25399213
TI  - The clinical utility of eye exam simulator in enhancing the competency of family
      physician residents in screening for diabetic retinopathy.
AB  - OBJECTIVES: To evaluate the utility of eye exam simulators in the training and
      assessment of family medicine residents for screening diabetic retinopathy (DR)
      utilizing direct ophthalmoscopy (DO). METHODS: This prospective, single arm,
      cross-sectional study was conducted at King AbdulAziz University Hospital,
      Jeddah, Kingdom of Saudi Arabia in April 2013, wherein the final year family
      medicine residents of the Saudi Board family medicine training program, underwent
      a practical session on DO using an eye exam simulator. The cognitive and motor
      skills of the participating family residents in performing DO, and their
      competency at diagnosing DR was assessed before, and after a practical session
      with the eye simulator. RESULTS: A total of 14 out of total 20 final year
      residents consented to join the study. Of these, 57.1% were females. A total of
      42.9% (6/14) showed initial motor skill competency, and 35.7% showed cognitive
      skill competency to diagnose DR. Before the session on the eye simulator, merely
      7.1% of the residents expressed confidence in performing DO. After the practical
      session, 78.6% (11/14) showed motor, and 64.3% (9/13) showed cognitive skill
      competency, in diagnosing DR. A total of 50% were adequately confident in
      performing DO. A total of 71.4% (10/14) of the residents preferred learning DO
      via simulation practical sessions than clinical rotation in ophthalmology
      clinics. CONCLUSION: Eye exam simulators are good tools in learning and
      assessment of DO skills leading to significant improvement in the efficiency and
      confidence of family physicians in screening for DR.

PMID- 25399214
TI  - Reference values for arterial stiffness indices in an Omani Arab population.
AB  - OBJECTIVES: To determine the reference values of arterial stiffness indices,
      particularly augmentation index (AIx) and pulse wave velocity (PWV) using
      applanation tonometry in a healthy Omani Arab population. METHODS: This
      prospective study was carried out in the Department of Clinical Physiology,
      Sultan Qaboos University Hospital, Muscat, Oman over a 2-year period from June
      2011 to June 2013. The central AIx, aortic PWV (AoPWV), and central pulse
      pressure (CPP) were recorded from 120 healthy subjects recruited randomly from a
      normal population using a SphygmoCor device. The 2.5th and 97.5th percentiles
      were used to determine the reference ranges for men and women separately.
      Analyses were performed using univariate statistics. RESULTS: The mean age of the
      cohort was 38 years for men, and 35 years for women, with the ages ranging from
      20-53 years. The overall mean central AIx was 13+/-11%, and for AoPWV was 6.7+/
      1.6 m/s. The central AIx was higher in women (17 versus 10%; p<0.001), whereas
      the AoPWV was higher in men (7.1 versus 6.3 m/s; p=0.003). Subjects were
      categorized according to the gender and age decade, and reference values for CPP,
      central AIx, and AoPWV were obtained. CONCLUSION: This study reports the
      reference values for arterial stiffness indices from an Omani Arab population;
      the results of which should be interpreted in the context of its limitations.

PMID- 25399215
TI  - Prevalence and severity of plaque-induced gingivitis in a Saudi adult population.
AB  - OBJECTIVES: To evaluate the prevalence and severity of plaque-induced gingivitis
      among a Saudi adult population in Riyadh region. METHODS: Three hundred and
      eighty-five eligible participants in this cross-sectional study were recruited
      from routine dental patients attending the oral diagnosis clinic at Al-Farabi
      College in Riyadh, Saudi Arabia from June 2013 to December 2013. A clinical
      examination was performed by 2 dentists to measure the gingival and plaque
      indices of Loe and Silness for each participant. RESULTS: The prevalence of
      gingivitis was 100% among adult subjects aged between 18-40 years old. Moreover,
      the mean gingival index was 1.68+/-0.31, which indicates a moderate gingival
      inflammation. In fact, males showed more severe signs of gingival inflammation
      compared with females (p=0.001). In addition, the mean plaque index was 0.875+/
      0.49, which indicates a good plaque status of the participants. Interestingly,
      the age was not related either to the gingival inflammation (p=0.13), or to the
      amount of plaque accumulation (p=0.17). However, males were more affected than
      females (p=0.005). CONCLUSION: The results of this study show that plaque
      accumulation is strongly associated with high prevalence of moderate to severe
      gingivitis among Saudi subjects. 

PMID- 25399216
TI  - Gingival biotype in relation to incisors' inclination and position.
AB  - OBJECTIVES: To study the association between gingival biotypes and inclination
      and position of the maxillary and mandibular incisors. METHODS: This cross
      sectional study included 142 consecutive orthodontic patients (64 males and 78
      females) who were seeking orthodontic treatment at the Faculty of Dentistry, King
      Abdulaziz University, Jeddah, Saudi Arabia from February 2013 to January 2014.
      Gingival biotype was assessed independently for the maxillary and mandibular
      central incisors using the transparency of periodontal probe method. Maxillary
      and mandibular incisors' inclination and position were measured using
      cephalometric analysis. RESULTS: The mean age was 23.56 (+/-2.55) years. The
      prevalence of thin gingival biotype was 43% for the maxillary and 52.1% for the
      mandibular incisors. Females were 4 times more likely to have thin gingiva for
      the maxillary incisors and 5 times more likely for the mandibular incisors. A
      significant association was found between mandibular incisor inclination and
      position and thin gingival biotype, while there was no association between the
      maxillary incisor inclination and position and gingival biotypes. CONCLUSION:
      Mandibular incisor proclination and protrusion is associated with thin gingival
      biotype while no association is found in the maxilla. The evaluation of the
      gingival biotype is essential during diagnosis and treatment planning for
      potential orthodontic patients. 

PMID- 25399217
TI  - Validity and reliability of an Arabic version of the modified dental anxiety
      scale in Saudi adults.
AB  - OBJECTIVES: To test the reliability and validity of an Arabic version of the
      modified dental anxiety scale (MDAS), and to correlate it with other demographic
      data. METHODS: The original English version of the MDAS was translated into
      Arabic, and then translated back into English by experienced bilingual
      professionals. Four hundred and seventy-four patients referred to dental clinics
      for treatment at the Faculty of Dentistry Hospital, Jeddah, Kingdom of Saudi
      Arabia from November 2012 to June 2013 participated in the study. The assessment
      tool included questions regarding demographic characteristics, frequency of
      dental visits, the Arabic version of the MDAS, and the patient's rating of their
      current level of anxiety using a visual analogue scale (VAS). RESULTS: The Arabic
      version of the MDAS had excellent internal consistency and reliability (Alpha
      coefficients >0.90). The scale was unidimensional, and the percentage of patients
      with dental anxiety was 48.3% (using a cutoff total score of >15) and with dental
      phobia was 2.5% (using a cutoff total score of >16). Younger patients, females,
      and infrequent visitors to the dentist were more anxious than those who were
      older, male, and frequent visitors. Visual analogue scale scores correlated
      significantly with individual items on the MDAS questionnaire and total anxiety
      score, supporting the criterion validity. CONCLUSION: The Arabic version of the
      MDAS presented adequate internal consistency reliability, allowing its safe use
      to assess levels of dental anxiety in Arabic-speaking populations.

PMID- 25399218
TI  - Malignant transformation of persistent endometriosis after hysterectomy.
AB  - The malignant transformation of persistent endometriotic implants into
      endometrioid adenocarcinoma is rare, especially after remote hysterectomy and
      salpingo-oophorectomy (TAH-BSO), and there are few cases reported in the English
      language literature. Patients receiving estrogen replacement therapy are common
      among the reported cases. We present a case that demonstrates the possibility of
      malignant transformation in a 53-year-old female, known case of endometriosis,
      who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy
      with no evidence of malignancy in the final pathology report. After 9 years, she
      presented with lower abdominal mass, and histopathological studies confirmed the
      diagnosis of well-differentiated endometrioid adenocarcinoma. The possibility of
      malignant transformation and possible risk factors are discussed with a brief
      literature review.  

PMID- 25399219
TI  - Toxic epidermal necrolysis in a patient receiving concurrent phenytoin and whole
      brain and thoracic radiotherapy.
AB  - Toxic epidermal necrolysis (TEN) is a severe drug induced type IV
      hypersensitivity syndrome that can be caused by anticonvulsant drugs, especially
      the aromatic anticonvulsants such as phenytoin. Most patients with brain
      metastasis receive whole brain radiotherapy along with anti-edema measures and
      anticonvulsants either as prophylactic or for symptom control; phenytoin being
      the most commonly used drug. In a subset of patients, cranial irradiation may act
      as a precipitating factor along with anticonvulsants for the development of TEN.
      We report a 54-year-old patient with metastatic non-small cell lung cancer
      treated with palliative whole brain and mediastinal radiotherapy with concurrent
      phenytoin-developing TEN, which started within the radiation portals with
      subsequent generalization. Though a rare, but serious complication, avoidance of
      the use of phenytoin concurrent with radiotherapy, replacing phenytoin with newer
      anticonvulsants, early recognition, aggressive management and awareness of this
      possible complication has been implied upon in this report.

PMID- 25399220
TI  - Cause analysis and therapeutic methods of chylous leakage after
      pancreaticoduodenectomy.
AB  - OBJECTIVES: To study and analyze the causes of chylous leakage after
      pancreaticoduodenectomy. METHODS: We retrospectively analyzed 381 patients who
      underwent pancreaticoduodenectomy (including pylorus-preserving
      pancreaticoduodenectomy) in Shanghai Chang Hai Hospital Affiliated to the Second
      Military Medical University, Shanghai, China between January 2010 and December
      2012.  We also studied the relationship between postoperative chylous leakage and
      age, gender, surgical approach, and the tumor nature. RESULTS: The chylous leak
      was placed in 23 patients and the incidence of chylous leakage in patients was
      0.6%. There was no significant difference in gender, age and tumor pathological
      pattern between the chylous leakage group and non-chylous leakage group. The
      incidence of chylous leakage in patients with N1 grade cancer was significantly
      higher than that in patients with N0 grade cancer (p=0.001). The incidence of
      chylous leakage in patients suffering R0 resection was significantly higher than
      that in patients suffering non-R0 resection (p=0.008). All patients were
      successfully treated conservatively. CONCLUSION: The incidence of chylous leakage
      was 0.6% and the chylous leakage was closely linked with the tumor's grade
      malignancy and the range of radical resection. 

PMID- 25399221
TI  - Does cesarean section have an impact on the successful initiation of
      breastfeeding in Saudi Arabia?
AB  - OBJECTIVES: To investigate whether the type of birth influenced breastfeeding
      outcomes. METHODS: This study used a quantitative descriptive correlation design
      study in a sample of 60 primigravida mothers. Participants were recruited over a
      2-month period from June to July 2011 in the postnatal ward at King AbdulAziz
      University Hospital (KAUH) in Jeddah city, Kingdom of Saudi Arabia (KSA).
      RESULTS: The results of the study indicated that women who gave birth vaginally
      were more likely to breastfeed within the first hour, and at 24 hours after birth
      than those who had a cesarean section. The mothers who had cesarean section
      stated that pain interfered with their ability to hold, breastfeed, and care for
      their baby. Healthy term babies at KAUH are routinely separated from their
      mothers, and given infant formula supplementation. CONCLUSION: The findings in
      this study reinforce the importance of appropriate pain management, keeping well
      babies with their mothers to remain together, 24 hours a day, and avoidance of
      non-medically indicated formula supplementation.

PMID- 25399222
TI  - Exenatide's effect in reducing weight and glycosylated hemoglobin level in an
      Arab population with type 2 diabetes.
AB  - OBJECTIVES: To determine whether exenatide is effective in reducing weight and
      glycosylated hemoglobin level (HbA1c), and to investigate its efficacy in
      improving lipid profile, blood pressure, and creatinine levels in the Arab
      population. METHODS: This study was conducted at the Endocrine Unit, Dubai
      Hospital, Dubai, United Arab Emirates. We retrospectively collected data from
      patients with type 2 diabetes started on exenatide between November 2011 and
      February 2012. Data included demographics, clinical, laboratory results, and
      medications used. A general linear model adjusted by baseline characteristics
      (weight, HbA1C, age, use of statins, and duration of diabetes) was used to assess
      changes between baseline and end of trial in HbA1C, weight, low density
      lipoprotein cholesterol, total cholesterol, triglycerides, creatinine, and blood
      pressure. RESULTS: After 6 months of treatment with exenatide, the HbA1c
      decreased by 0.47% (95% confidence level [CI]: -0.01 - 0.95) (p=0.055). Weight
      reduction was highly significant; 5.6 kg (95% CI: 3.34 - 7.85) (p<0.001). Those
      reductions remained significant after adjustment for confounding factors.
      CONCLUSION: This study showed that weight reduction was highly significant with
      exenatide. The borderline significance in HbA1c reduction can be attributed to
      the small sample size. 

PMID- 25399223
TI  - Prevalence of Helicobacter pylori and parasites in symptomatic children examined
      for Helicobacter pylori antibodies, antigens, and parasites in Yemen.
AB  - OBJECTIVES: To estimate the prevalence of Helicobacter pylori (H. pylori) and
      parasites in symptomatic children examined for H. pylori antibodies, antigens,
      and parasites in Yemen. METHODS: A record-based study was carried out at
      Specialized Sam Pediatric Center in Sana'a, Yemen for 3 years between 2011-2013.
      Out of the 43,200 patients seen for different causes through that period, 1008
      (2.3%) (females: 675 [67%]; males: 333 [33%]) had gastric complaints, and were
      subjected to an examination of blood and stool for H. pylori and parasites. Data
      regarding age and gender was also collected. RESULTS: The age of the patients
      ranged from 3-15 years. The prevalence of H. pylori among children examined for
      H. pylori was 65%, 30% of them were males, and 35% were females (chi square
      [I2]=142, p<0.01]). The prevalence in the 6-8 years age group was 83%, and it was
      52% in the age group of 12-15 years. The prevalence of giardiasis was 10%, and
      amoebiasis was 25%. CONCLUSION: Prevalence of H. pylori infection among children
      was high, and was more prevalent in the age group of 6-8 years than in the other
      age groups. Females were more affected than males. Parasites (amoebiasis and
      giardiasis) infestation was less prevalent.

PMID- 25399224
TI  - Site-specific mouth rinsing can improve oral odor by altering bacterial counts.
      Blind crossover clinical study.
AB  - OBJECTIVES: To determine whether site-specific mouth rinsing with oral
      disinfectants can improve oral odor beyond the traditional panoral mouth
      disinfection with mouth rinses by targeting specifically oral malodor implicated
      anaerobic bacteria. METHODS: Twenty healthy fasting subjects volunteered for a
      blinded prospective, descriptive correlational crossover cross-section clinical
      trial conducted during the month of Ramadan between July and August 2013 in
      Albaha province in Saudi Arabia involving the application of Listerine Cool Mint
      mouth rinse by either the traditional panoral rinsing method, or a site-specific
      disinfection method targeting the subgingival and supragingival plaque and the
      posterior third of the tongue dorsum, while avoiding the remaining locations
      within the oral cavity. The viable anaerobic and aerobic bacterial counts,
      volatile sulfur compounds (VSCs) levels, organoleptic assessment of oral odor,
      and the tongue-coating index were compared at baseline, one, 5, and 9 hours after
      the treatment. RESULTS: The site-specific disinfection method reduced the VSCs
      and anaerobic bacterial loads while keeping the aerobic bacterial numbers higher
      than the traditional panoral rinsing method. CONCLUSION: Site-specific
      disinfection can more effectively maintain a healthy oral cavity by predominantly
      disinfecting the niches of anaerobic bacteria within the oral cavity.

PMID- 25399225
TI  - Mass lesion in a chest x-ray of a male adolescent. Round pneumonia.

PMID- 25399226
TI  - Acute hemiplegia as a rare presentation of infantile Guillain-Barre syndrome.

PMID- 25399228
TI  - The frequency of the BLM p.Q548X (c.1642C>T) mutation in breast cancer patients
      from Russia is no higher than in the general population.

PMID- 25399229
TI  - Dose-dense paclitaxel versus docetaxel following FEC as adjuvant chemotherapy in
      axillary node-positive early breast cancer: a multicenter randomized study of the
      Hellenic Oncology Research Group (HORG).
AB  - Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in
      node-positive early breast cancer. However, which is the preferable taxane in a
      dose-dense regimen remains unknown. We conducted a randomized study to compare
      the efficacy of dose-dense paclitaxel versus docetaxel following 5-fluorouracil,
      epirubicin, and cyclophosphamide (FEC) as adjuvant chemotherapy in women with
      node-positive early breast cancer. Following surgery women with HER2-negative
      breast cancer and at least one infiltrated axillary lymph node were randomized to
      receive four cycles of FEC (700/75/700 mg/m(2)) followed by four cycles of either
      paclitaxel (175 mg/m(2)) or docetaxel (75 mg/m(2)). All cycles were administered
      every 14 days with G-CSF support. The primary endpoint was disease-free survival
      (DFS) at 3 years. Between 2004 and 2007, 481 women were randomized to paclitaxel
      (n = 241) and docetaxel (n = 240). After a median follow-up of 6 years, 51 (21%)
      and 48 (20%) women experienced disease relapse (p = 0.753) and there was no
      significant difference in DFS between the paclitaxel- and docetaxel-treated
      groups (3-year DFS 87.4 vs. 88.3%, respectively; median DFS not reached; p =
      0.633). Toxicities were manageable, with grade 2-4 neutropenia in 21 versus 31%
      (p = 0.01), thrombocytopenia 0.8 versus 3.4% (p = 0.06), any grade neurotoxicity
      17 versus 7.5% (p = 0.35) and onycholysis 4.9 versus 12.1% (p = 0.03) for
      patients receiving paclitaxel and docetaxel, respectively. There were no toxic
      deaths. Dose-dense paclitaxel versus docetaxel after FEC as adjuvant chemotherapy
      results in a similar 3-year DFS rate in women with axillary node-positive early
      breast cancer. Due to its more favorable toxicity profile, paclitaxel is the
      taxane of choice in this setting.

PMID- 25399230
TI  - Association between persistence with mammography screening and stage at diagnosis
      among elderly women diagnosed with breast cancer.
AB  - Previous studies on the association between mammography screening and stage at
      breast cancer (BC) diagnosis have limitations because they did not analyze
      persistence with mammography screening and did not distinguish screening from
      diagnostic mammograms. The objective of this study is to determine the
      association between persistence with mammography screening and stage at BC
      diagnosis among elderly women. A retrospective observational study of 39,006
      women age >=70 diagnosed with incident BC from 2005 to 2009 from the
      Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset was
      conducted. A validated algorithm with high sensitivity and specificity was used
      to distinguish between screening and diagnostic mammograms. Persistence with
      mammography screening was measured as having at least three screening mammograms
      in five years before BC diagnosis. Multinomial logistic regressions were
      performed to analyze the association between persistence with mammography
      screening and stage at diagnosis, in a multivariate framework. Overall, 46% of
      elderly women were persistent with mammography screening, 26% were not
      persistent, and 28% did not have any screening mammogram in five years before BC
      diagnosis. As compared to women who were not persistent with mammography
      screening, women who were persistent with mammography screening were
      significantly more likely to be diagnosed at earlier stages of BC. The adjusted
      odds ratios were 3.28, 2.37, and 1.60 for in situ, local, and regional stages,
      respectively. A lower proportion of elderly women was persistent with mammography
      and it was highly associated with earlier stages of BC diagnosis. Interventions
      designed to promote persistent mammography screening among elderly women are
      warranted.

PMID- 25399231
TI  - Degree of urbanization and mammographic density in Dutch breast cancer screening
      participants: results from the EPIC-NL cohort.
AB  - It has been observed that women living in urban areas have a higher mammographic
      density (MD) compared to women living in rural areas. This association might be
      explained by regional differences in reproductive and lifestyle factors or
      perhaps by variation in exposure to ambient air pollution as air pollution
      particles have been described to show estrogenic activity. We investigated the
      association between degree of urbanization and MD, and aimed to unravel the
      underlying etiology. 2,543 EPIC-NL participants were studied, and general linear
      models were used. Urbanization was categorized into five categories according to
      the number of addresses/km(2). Information on reproductive and lifestyle factors
      was obtained from the recruitment questionnaire. Air pollution exposure was
      estimated using land-use regression models. MD was expressed as percent density
      (PD) and dense area (DA), and was quantified using Cumulus. Women living in
      extremely urbanized areas had a higher PD (21.4%, 95% confidence interval (CI)
      20.5-22.3%) compared to women living in not urbanized areas (16.1, 95% CI 14.5
      17.8%, P trend < 0.01).The association persisted after adjustment for
      reproductive and lifestyle factors as well as for individual exposure to air
      pollution (adjusted PDextremely_urbanized = 22.1%, 95% CI 18.0-26.5% versus
      adjusted PDnot_urbanized = 16.9%, 95% CI 13.0-21.2, P trend < 0.01).The results
      for DA showed close similarity to the results for PD. We found evidence that
      degree of urbanization is associated with MD. The association could not be
      explained by differences in reproductive and lifestyle factors or by variation in
      air pollution exposure.

PMID- 25399232
TI  - Impact of histological subtype on long-term outcomes of neuroendocrine carcinoma
      of the breast.
AB  - Although rare, neuroendocrine carcinoma of the breast (NECB) is becoming an
      increasingly recognized entity. The current literature is limited to case reports
      and small series and therefore a comprehensive population-based analysis was
      conducted to investigate the clinicopathologic features and long-term outcomes
      associated with NECB. We included all patients in the SEER Database from 2003 to
      2010 with a diagnosis of NECB. The 2012 WHO classification system was used to
      categorize patients based on histopathologic diagnosis: well-differentiated
      neuroendocrine tumors, small/oat cell or poorly differentiated neuroendocrine
      tumors, adenocarcinoma with neuroendocrine features (ANF), large cell
      neuroendocrine and carcinoid tumors. Survival analysis was performed for disease
      specific (DSS) and overall (OS) survival. Of the 284 cases identified, 52.1% were
      classified as well-differentiated, 25.7% small cell, 14.8% ANF, 4.9% large cell,
      and 2.5% carcinoid. In general, patients presented with advanced disease: 36.2%
      had positive lymph node metastases and 20.4% presented with systemic metastases.
      Five-year DSS rates for stage I-IV NECB were 88.1, 67.8, 60.5, and 12.4%,
      respectively, while five-year OS rates were 77.9, 57.3, 52.9, and 8.9%,
      respectively. DSS and OS were significantly different for well-differentiated
      neuroendocrine tumors and ANFs compared to small cell and carcinoid tumors. On
      univariate Cox proportional hazards regression, small cell carcinoma was
      significantly associated with worse DSS (OR 1.97, 95% CI 1.05-3.67) and OS (OR
      2.66, 95% CI 1.49-4.72) compared to other neuroendocrine tumors. NECB is
      associated with advanced stage disease at presentation and an unfavorable
      prognosis for stage II-IV disease and small cell, large cell, and carcinoid
      histologic subtypes.

PMID- 25399233
TI  - Apparent diffusion coefficient quantification as an early imaging biomarker of
      response for unresectable infiltrative hepatocellular carcinoma.

PMID- 25399234
TI  - Use of transabdominal ultrasonography to preoperatively determine T-stage of
      proven colon cancers.
AB  - PURPOSE: Although noninvasive and highly informative, transabdominal
      ultrasonography (US) is not yet an accepted means of staging colorectal cancer
      preoperatively. This prospective study evaluated the diagnostic accuracy of US in
      preoperative staging of patients with resectable colon cancers. METHODS: A total
      of 98 patients with primary colon cancer diagnosed by colonoscopy at our
      institute between January, 2011 and June, 2014 underwent preoperative
      ultrasonographic tumor staging. Depth of tumor infiltration (T-stage) was
      assessed by standard means (i.e., extent of mural involvement), analyzing
      agreement in US and histopathology determinations. RESULTS: All but two colon
      cancers (at splenic flexure) were detected by US (98%, 96/98). Compared with
      histopathology, overall accuracy of US in determining T-stage was 64% (61/96),
      indicating moderate reproducibility (kappa coefficient 0.48; 95% CI 0.35-0.62; p
      < 0.001). Using a three-tier approach of graded muscularis propria (MP)
      involvement (Tis/T1, below MP; T2, within MP; and T3/T4, beyond MP), diagnostic
      agreement increased to 89% (85/96), with good agreement (kappa coefficient 0.77;
      95% CI 0.64-0.90; p < 0.001). No tumor characteristics or patient demographics
      influenced diagnostic agreement at any site in the colon. CONCLUSIONS: Given the
      potential to yield valuable information while limiting patient discomfort, US
      should be reconsidered as a means of assessing colon cancer.

PMID- 25399235
TI  - Low energy conformations for gonadotropin-releasing hormone with D- and L-amino
      acid substitutions for Gly 6: possible receptor-bound conformations.
AB  - In the preceding paper, using ECEPP, including the effects of water, and the
      chain build-up procedure, we computed the low energy structures for GnRH and
      found that there were no distinct low energy structures or structures with high
      statistical weights. To attempt to deduce possible structures of GnRH that may
      bind to the GnRH receptor, we computed the low energy structures for GnRH
      peptides that have L- and D-amino acids substituting for Gly 6. The L-amino acid
      substituted peptides (L-Ala and L-Val) have very low or no affinity for the
      receptor and on activity (release of FSH and LH) while the D-Ala-, D-Leu-, D-Trp-
      and D-Phe-substituted peptides have significantly higher relative affinities and
      activities than those for native GnRH; the D-Val-substituted peptide has about
      one-third of the affinity and activity as native GnRH. Unlike native GnRH, our
      computations suggest that both sets of peptides form well-defined structures in
      water: the L-amino acid-substituted peptides are predominantly alpha-helical
      while the D-amino acid-substituted peptides adopted E*A A A E D*(C*) A E C A(C*)
      and minor variants of these structures. By eliminating structures that lay in
      common to the D-Ala and L-Val peptides and further eliminating structures that
      differed between the D-Ala and D-Leu peptides, we reduced the number of possible
      distinct binding conformations to 254. Searching for structures among these 254
      conformations that had relative statistical weights that paralleled their
      relative affinities, we found two candidate structures: D*E A A E C*A E C A and
      D*G A A E D*A E C G*, both of which have conformations for residues 3-9 that are
      similar to the computed most probable structures for the D-amino acid-substituted
      GnRH peptides in water. 

PMID- 25399237
TI  - Asperger syndrome and nonverbal learning difficulties in adult males: self- and
      parent-reported autism, attention and executive problems.
AB  - A specific overlap between Asperger syndrome (AS) and nonverbal learning
      difficulties (NLD) has been proposed, based on the observation that, as a group,
      people with AS tend to have significantly higher verbal IQ (VIQ) than performance
      IQ (PIQ), one of the core features of NLD. The primary aim was to assess the
      longer term outcome of NLD--broken down into persistent and transient forms. The
      present study of 68 individuals was performed in the context of a larger
      prospective longitudinal study to late adolescence/early adult life of 100 boys
      with AS. Using self- and parent-report measures, we studied the longer term
      outcome of the NLD (defined as VIQ > PIQ by 15 points) as regards social
      communication, repetitive behaviour, attention, and executive function (EF) was
      studied. Three subgroups were identified: (1) Persistent NLD (P-NLD), (2)
      Childhood "only" NLD (CO-NLD) and (3) Never NLD (NO-NLD). The P-NLD group had the
      worst outcome overall. The CO-NLD group had better reported EF scores than the
      two other AS subgroups. There were no differences between the subgroups regarding
      social communication, repetitive behaviour, or attentional skills. Low PIQ
      increased the risk of ADHD symptoms. In the context of AS in males, P-NLD carries
      a relatively poor outcome, particularly with regard to self-reported EF. However,
      CO-NLD appears to entail a significantly better outcome. The results underscore
      the importance of analysing the cognitive profile both at diagnosis and after
      several years, so as to be able to formulate a realistic prognosis.

PMID- 25399236
TI  - Altered distribution of hippocampal interneurons in the murine Down Syndrome
      model Ts65Dn.
AB  - Down Syndrome, with an incidence of one in 800 live births, is the most common
      genetic alteration producing intellectual disability. We have used the Ts65Dn
      model, that mimics some of the alterations observed in Down Syndrome. This
      genetic alteration induces an imbalance between excitation and inhibition that
      has been suggested as responsible for the cognitive impairment present in this
      syndrome. The hippocampus has a crucial role in memory processing and is an
      important area to analyze this imbalance. In this report we have analysed, in the
      hippocampus of Ts65Dn mice, the expression of synaptic markers: synaptophysin,
      vesicular glutamate transporter-1 and isoform 67 of the glutamic acid
      decarboxylase; and of different subtypes of inhibitory neurons (Calbindin D-28k,
      parvalbumin, calretinin, NPY, CCK, VIP and somatostatin). We have observed
      alterations in the inhibitory neuropil in the hippocampus of Ts65Dn mice. There
      was an excess of inhibitory puncta and a reduction of the excitatory ones. In
      agreement with this observation, we have observed an increase in the number of
      inhibitory neurons in CA1 and CA3, mainly interneurons expressing calbindin,
      calretinin, NPY and VIP, whereas parvalbumin cell numbers were not affected.
      These alterations in the number of interneurons, but especially the alterations
      in the proportion of the different types, may influence the normal function of
      inhibitory circuits and underlie the cognitive deficits observed in DS. 

PMID- 25399238
TI  - Urinary incontinence and poor functional status in fragility fracture patients:
      an underrecognized and underappreciated association.
AB  - PURPOSE/INTRODUCTION: Urinary incontinence (UI) affects some 20 % of community
      dwelling older people and 30-60 % of people in institutional care. UI is known as
      an independent predictor of falls, and likely impacts fracture rates. The aim of
      the study was to measure the prevalence of UI in a typical fragility fracture
      population, to evaluate the relationship of UI with functional disability in the
      post-acute setting. METHODS: Our study is a retrospective cross-sectional study
      of patients admitted to rehabilitation setting after inpatient hospital
      management for a fragility fracture. We included all consecutively admitted
      fragility fracture patients aged over 65. All patients underwent standard
      clinical examination and Geriatric Assessment. We assessed UI using a two-stage
      process with a six-item UI screening questionnaire followed by an interview.
      RESULTS: 1,857 (80.7 % female) patients were available for analysis, mean age was
      81.7 years. UI was identified in 59.2 % of all fragility fracture patients, and
      was more prevalent in females. Patients suffering from UI differed significantly
      in almost all measured functional and cognitive tests, with increased
      dependency/lower ADL scores, increased rates of immobility, and higher rates of
      cognitive dysfunction and depression. CONCLUSION: This study confirms the high
      prevalence of UI in older fragility fracture patients, and the association
      between UI and functional impairments. The diagnostic work-up and treatment of
      patients should be focused on the special needs of these older patients. More
      efforts are needed to increase awareness about prevalence and consequences of UI
      among older fragility fracture patients.

PMID- 25399239
TI  - Identifying key domains of health-related quality of life for patients with
      chronic obstructive pulmonary disease: interviews with healthcare professionals.
AB  - PURPOSE: The aim of this paper is to identify which domains of health-related
      quality of life (HRQoL) are most important for patients with chronic obstructive
      pulmonary disease (COPD), from the perspective of healthcare professionals
      (HCPs). METHODS: Thirteen Dutch HCPs [six pulmonologists, three pulmonology nurse
      practitioners, two physiotherapists and two general practitioners; 9 men; mean
      age 51.0 (SD = 10.6) years; mean years of experience 12.1 (SD = 7.2)] specialized
      in the field of COPD were recruited. The only inclusion criterion was that the
      HCP had to have extensive experience in treating COPD patients. The face-to-face
      interviews took 30-40 min. RESULTS: Physical health emerged as the most important
      theme from the spontaneous statements that HCPs made when asked about HRQoL in
      relation to COPD, closely followed by social health and coping with COPD-related
      complaints and restrictions. The most frequently selected PROMIS domains were
      fatigue, physical function, emotional support and depression. If the related
      domains satisfaction with participation in social roles and activities and
      ability to participate in social roles and activities were to be combined, it
      would come in second place after fatigue. CONCLUSION: When comparing the domains
      chosen by HCPs to the ones chosen by patients in a recent study, there is a high
      degree of agreement, with the exception of depression. We argue that it is
      important to take into account both patient and HCP perspective when
      developing/selecting HRQoL instruments. Our results may be used to inform domain
      selection to measure HRQoL in patients with COPD, as well as instrument
      development.

PMID- 25399240
TI  - Health system challenges of NCDs in Tunisia.
AB  - OBJECTIVES: The objective of this study was to present a qualitative 'situation
      analysis' of the healthcare system in Tunisia, as it applies to management of
      cardiovascular disease (CVD) and diabetes. A primary concern was the
      institutional capacity to manage non-communicable diseases (NCDs). METHODS:
      Research took place during 2010 (analysis of official documents, semi-structured
      interviews with key informants, and case studies in four clinics). Walt and
      Gilson's framework (1994) for policy analysis was used: content, actors, context,
      and process. RESULTS: Problems of integration and coordination have compounded
      funding pressures. Despite its importance in Tunisian healthcare, primary health
      is ill-equipped to manage NCDs. With limited funds, and no referral or health
      information system, staff morale in the public sector was low. Private healthcare
      has been the main development filling the void. CONCLUSION: This study highlights
      major gaps in the implementation of a comprehensive approach to NCDs, which is an
      urgent task across the region. In strategic planning, research on the health
      system is vital; but the capacity within Ministries of Health to use research has
      first to be built, with a commitment to grounding policy change in evidence.

PMID- 25399241
TI  - Acupuncture for overactive bladder in female adult: a randomized controlled
      trial.
AB  - PURPOSE: To assess the effectiveness of acupuncture in treating female adult with
      overactive bladder. MATERIALS AND METHODS: After we excluded other causes for
      storage symptoms, a total of 240 consecutive female patients with overactive
      bladder were enrolled and completed all aspects of this prospective randomized
      controlled trial, of which 118 cases were randomly assigned to receive a weekly
      acupuncture treatment (intervention group), while the other 122 cases were given
      a pharmacological treatment of oral tolterodine tartrate 2 mg twice daily
      (control group) for 4 weeks. Data on urgency, incontinence, micturition
      frequency, nocturia episodes and voided volume were collected and statistically
      analyzed before and after 4 weekly acupuncture treatments or 4 weeks'
      pharmacological treatment using a 3-day micturition diary. RESULTS: The two
      groups of female patients with overactive bladder were given treatment with
      weekly acupuncture (n = 118), oral tolterodine tartrate (n = 122) for 4 weeks
      respectively. At weeks 4, subjects in both intervention and control groups had
      significant decreases in number of urinary urgency episodes, incontinence
      episodes, daytime frequency, nocturia episodes and increase in volume voided per
      micturition without a significant difference in the changes of overactive bladder
      symptoms between the groups. There were no serious adverse events during the
      study. CONCLUSIONS: This randomized controlled trial demonstrates that
      acupuncture is safe with significant improvements in patient assessment of
      overactive bladder symptoms and may be considered a clinically alternative
      treatment for overactive bladder in female adult.

PMID- 25399242
TI  - Longitudinal follow-up of Riata leads reveals high annual incidence of new
      conductor externalization and electrical failure.
AB  - BACKGROUND AND PURPOSE: Riata(TM) defibrillation leads are susceptible to
      conductor externalization. The point prevalence of insulation defect in Riata(TM)
      leads is up to 33 %, but prospective data concerning incidence of new lead
      abnormalities are lacking. The purpose of our study was to determine the annual
      incidence of new conductor externalizations and electrical lead failure. METHODS:
      A prospective observational study was conducted at a single tertiary center. One
      hundred forty-one patients were followed over 12 months. A posterior-anterior
      (PA)/lateral chest x-ray (CXR) with zooming was performed at baseline and at 12
      months to screen for conductor externalization. Electrical abnormalities and
      clinical outcome were also assessed. RESULTS: The overall incidence of new
      insulation defects was 8.5 % at 12 months. High-risk leads for new conductor
      externalization were lead models 1580, 1582, and 1590 with an annual rate of
      11.9, 11.1, and 10 %, respectively. New conductor externalizations were three
      times more common in 8 Fr leads compared to 7 Fr leads. The overall incidence of
      new electrical dysfunction was 6.4 % at 12 months. Electrical dysfunction was
      significantly higher in abnormal leads (25 % [3/12], 4.7 % [6/129]; p = 0.03) and
      mostly driven by high ventricular pacing thresholds. There was no difference in
      inappropriate shock or failure of high-voltage therapy. CONCLUSION: The annual
      incidence of new insulation defects in Riata(TM) leads is much higher than
      previously reported. Lead models 1580, 1582, and 1590 are at highest risk for new
      conductor externalization. Electrical dysfunction in Riata(TM) leads is also much
      higher than reported and is associated with conductor externalization.

PMID- 25399243
TI  - Benefits of gregarious feeding by aposematic caterpillars depend on group age
      structure.
AB  - Gregarious feeding is a common feature of herbivorous insects and can range from
      beneficial (e.g. dilution of predation risk) to costly (e.g. competition). Group
      age structure should influence these costs and benefits, particularly when old
      and young larvae differ in their feeding mode or apparency to predators. We
      investigated the relative value of gregarious feeding by aposematic larvae of
      Uresiphita reversalis that we observed feeding in groups of mixed ages and
      variable densities on wild Lupinus diffusus. In a manipulative field experiment,
      the survivorship and growth of young larvae were enhanced in the presence of
      older conspecifics, but not in large groups of similarly aged larvae. Estimates
      of insect damage and induced plant responses suggest that mixed-age groups
      enhance plant quality for young larvae while avoiding competition. We conclude
      that benefits of gregariousness in this species are contingent on group age
      structure, a finding of significance for the ecology and evolution of
      gregariousness and other social behaviours. 

PMID- 25399244
TI  - Temporal coordination in joint music performance: effects of endogenous rhythms
      and auditory feedback.
AB  - Many behaviors require that individuals coordinate the timing of their actions
      with others. The current study investigated the role of two factors in temporal
      coordination of joint music performance: differences in partners' spontaneous
      (uncued) rate and auditory feedback generated by oneself and one's partner.
      Pianists performed melodies independently (in a Solo condition), and with a
      partner (in a duet condition), either at the same time as a partner (Unison), or
      at a temporal offset (Round), such that pianists heard their partner produce a
      serially shifted copy of their own sequence. Access to self-produced auditory
      information during duet performance was manipulated as well: Performers heard
      either full auditory feedback (Full), or only feedback from their partner
      (Other). Larger differences in partners' spontaneous rates of Solo performances
      were associated with larger asynchronies (less effective synchronization) during
      duet performance. Auditory feedback also influenced temporal coordination of duet
      performance: Pianists were more coordinated (smaller tone onset asynchronies and
      more mutual adaptation) during duet performances when self-generated auditory
      feedback aligned with partner-generated feedback (Unison) than when it did not
      (Round). Removal of self-feedback disrupted coordination (larger tone onset
      asynchronies) during Round performances only. Together, findings suggest that
      differences in partners' spontaneous rates of Solo performances, as well as
      differences in self- and partner-generated auditory feedback, influence temporal
      coordination of joint sensorimotor behaviors. 

PMID- 25399248
TI  - Investing in longitudinal studies of primary healthcare: what can we learn about
      service performance, sustainability and quality?

PMID- 25399245
TI  - Neural summation in human motor cortex by subthreshold transcranial magnetic
      stimulations.
AB  - Integration of diverse synaptic inputs is a basic neuronal operation that relies
      on many neurocomputational principles, one of which is neural summation. However,
      we lack empirical understanding of neuronal summation in the human brains in
      vivo. Here, we explored the effect of neural summation on the motor cortex using
      two subthreshold pulses of transcranial magnetic stimulation (TMS), each with
      intensities ranging from 60 to 95% of the resting motor threshold (RMT) and
      interstimulus interval (ISI) varying from 1 to 25 ms. We found that two
      subthreshold TMS pulses can produce suprathreshold motor response when ISIs were
      less than 10 ms, most prominent at 1, 1.5 and 3 ms. This facilitatory, above
      threshold response was evident when the intensity of the subthreshold pulses was
      above 80% of RMT but was absent as the intensity was 70% or below. Modeling of
      the summation data across intensity suggested that they followed an exponential
      function with excellent model fitting. Understanding the constraints for inducing
      summation of subthreshold stimulations to generate above-threshold response may
      have implications in modeling neural operations and potential clinical
      applications.

PMID- 25399249
TI  - Assessment-driven selection and adaptation of exercise difficulty in robot
      assisted therapy: a pilot study with a hand rehabilitation robot.
AB  - BACKGROUND: Selecting and maintaining an engaging and challenging training
      difficulty level in robot-assisted stroke rehabilitation remains an open
      challenge. Despite the ability of robotic systems to provide objective and
      accurate measures of function and performance, the selection and adaptation of
      exercise difficulty levels is typically left to the experience of the supervising
      therapist. METHODS: We introduce a patient-tailored and adaptive robot-assisted
      therapy concept to optimally challenge patients from the very first session and
      throughout therapy progress. The concept is evaluated within a four-week pilot
      study in six subacute stroke patients performing robot-assisted rehabilitation of
      hand function. Robotic assessments of both motor and sensory impairments of hand
      function conducted prior to the therapy are used to adjust exercise parameters
      and customize difficulty levels. During therapy progression, an automated routine
      adapts difficulty levels from session to session to maintain patients'
      performance around a target level of 70%, to optimally balance motivation and
      challenge. RESULTS: Robotic assessments suggested large differences in patients'
      sensorimotor abilities that are not captured by clinical assessments. Exercise
      customization based on these assessments resulted in an average initial exercise
      performance around 70% (62% +/- 20%, mean +/- std), which was maintained
      throughout the course of the therapy (64% +/- 21%). Patients showed reduction in
      both motor and sensory impairments compared to baseline as measured by clinical
      and robotic assessments. The progress in difficulty levels correlated with
      improvements in a clinical impairment scale (Fugl-Meyer Assessment) (r s = 0.70),
      suggesting that the proposed therapy was effective at reducing sensorimotor
      impairment. CONCLUSIONS: Initial robotic assessments combined with progressive
      difficulty adaptation have the potential to automatically tailor robot-assisted
      rehabilitation to the individual patient. This results in optimal challenge and
      engagement of the patient, may facilitate sensorimotor recovery after
      neurological injury, and has implications for unsupervised robot-assisted therapy
      in the clinic and home environment. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02096445.

PMID- 25399250
TI  - Acute inflammatory response in the subcutaneous versus periprosthethic space
      after incisional hernia repair: an original article.
AB  - BACKGROUND: The acute inflammatory response following mesh implantation has been
      often evaluated in vitro and in animal models. The aim of this study was to
      evaluate the acute inflammatory response near the prosthesis in human by
      analysing some inflammatory indicators. METHODS: We used a cohort of twelve male
      patients affected by midline incisional hernia, who were admitted for surgical
      mesh repair. A suction drain was placed between the mesh and rectal muscles
      whereas, the other one was placed between the subcutaneous tissue and the oblique
      external sheath. The acute inflammatory response was analyzed by measuring the
      production of interleukin [IL]-1, IL-10, IL-1ra, C-Reactive Protein (CRP), total
      proteins, albumin and pH in the drain fluids. RESULTS: The dynamics of CRP and
      ILs production resulted similar in both drainages. Comparing drain over mesh and
      subcutaneous drain at all times, IL-1 and CRP values always resulted
      significantly higher in the first one, whereas IL-1ra and IL-10 values were
      significantly higher in the last one. Total protein and albumin were similar in
      both drains at all time; only in the drain over mesh fluid, pH values resulted
      significantly reduced in the fourth post-operative day. CONCLUSIONS: Our data
      showed that an acute inflammatory reaction is present in both sites examined.
      However, it was significantly higher in the space after mesh implantation.

PMID- 25399251
TI  - Sugar metabolism, chip color, invertase activity, and gene expression during long
      term cold storage of potato (Solanum tuberosum) tubers from wild-type and
      vacuolar invertase silencing lines of Katahdin.
AB  - BACKGROUND: Storing potato tubers at low temperatures minimizes sprouting and
      disease but can cause an accumulation of reducing sugars in a process called cold
      induced sweetening. Tubers with increased amounts of reducing sugars produce dark
      colored, bitter-tasting fried products with elevated amounts of acrylamide, a
      possible carcinogen. Vacuolar invertase (VInv), which converts sucrose produced
      by starch breakdown to glucose and fructose, is the key determinant of reducing
      sugar accumulation during cold-induced sweetening. In this study, wild-type
      tubers and tubers in which VInv expression was reduced by RNA interference were
      used to investigate time- and temperature-dependent changes in sugar contents,
      chip color, and expression of VInv and other genes involved in starch metabolism
      in tubers during long-term cold storage. RESULTS: VInv activities and tuber
      reducing sugar contents were much lower, and tuber sucrose contents were much
      higher, in transgenic than in wild-type tubers stored at 3-9 degrees C for up to
      eight months. Large differences in VInv mRNA accumulation were not observed at
      later times in storage, especially at temperatures below 9 degrees C, so
      differences in invertase activity were likely established early in the storage
      period and maintained by stability of the invertase protein. Sugar contents, chip
      color, and expression of several of the studied genes, including AGPase and GBSS,
      were affected by storage temperature in both wild-type and transgenic tubers.
      Though transcript accumulation for other sugar-metabolism genes was affected by
      storage temperature and duration, it was essentially unaffected by invertase
      silencing and altered sugar contents. Differences in stem- and bud-end sugar
      contents in wild-type and transgenic tubers suggested different
      compartmentalization of sucrose at the two ends of stored tubers. CONCLUSIONS:
      VInv silencing significantly reduced cold-induced sweetening in stored potato
      tubers, likely by means of differential VInv expression early in storage.
      Transgenic tubers retained sensitivity to storage temperature, and accumulated
      greater amounts of sucrose, glucose and fructose at 3 degrees C than at 7-9
      degrees C. At each storage temperature, suppression of VInv expression and large
      differences in tuber sugar contents had no effect on expression of AGPase and
      GBSS, genes involved in starch metabolism, suggesting that transcription of these
      genes is not regulated by tuber sugar content.

PMID- 25399252
TI  - Neovaginal perforation following sexual intercourse in a transsexual patient.
AB  - BACKGROUND: Neovaginal perforation can develop following sexual intercourse in
      patients that have undergone male to female gender reassignment surgery. In such
      cases urinary tract symptoms may mimic acute cystitis and acute pyelonephritis.
      CASE PRESENTATION: A 33-year old white transsexual patient presented to the
      emergency department with dysuria, hematuria, difficulty urinating, widespread
      groin pain, bilateral side pain, clear vaginal discharge, abdominal pain, and
      nausea 2-3 h after sexual intercourse. Abdominal tomography showed fluid around
      the vaginal cuff and air throughout the abdomen. Vaginography showed contrast
      leaking to the abdomen from the vaginal cuff. The patient was considered as
      vaginal perforation and admitted to clinic. CONCLUSION: Vaginal perforation
      should be considered in transsexual patients that develop urinary system symptoms
      following sexual intercourse. Such cases were treated medically without the need
      surgery.

PMID- 25399253
TI  - Association of physical function with predialysis blood pressure in patients on
      hemodialysis.
AB  - BACKGROUND: New information from various clinical settings suggests that tight
      blood pressure control may not reduce mortality and may be associated with more
      side effects. METHODS: We performed cross-sectional multivariable ordered
      logistic regression to examine the association between predialysis blood pressure
      and the short physical performance battery (SPPB) in a cohort of 749 prevalent
      hemodialysis patients in the San Francisco and Atlanta areas recruited from July
      2009 to August 2011 to study the relationship between systolic blood pressure and
      objective measures of physical function. Mean blood pressure for three
      hemodialysis sessions was analyzed in the following categories: <110 mmHg, 110
      129 mmHg (reference), 130-159 mmHg, and >=160 mmHg. SPPB includes three
      components: timed repeated chair stands, timed 15-ft walk, and balance tests.
      SPPB was categorized into ordinal groups (<=6, 7-9, 10-12) based on prior
      literature. RESULTS: Patients with blood pressure 130-159 mmHg had lower odds (OR
      0.57, 95% CI 0.35-0.93) of scoring in a lower SPPB category than those whose
      blood pressure was between 110 and 129 mmHg, while those with blood pressure>=160
      mmHg had 0.56 times odds (95% CI 0.33-0.94) of scoring in a lower category when
      compared with blood pressure 110-129 mmHg. When individual components were
      examined, blood pressure was significantly associated with chair stand (130-159
      mmHg: OR 0.59, 95% CI 0.38-0.92) and gait speed (>=160 mmHg: OR 0.59, 95% CI 0.35
      0.98). Blood pressure>=160 mmHg was not associated with substantially higher SPPB
      score compared with 130-159 mmHg. CONCLUSIONS: Patients with systolic blood
      pressure at or above 130 mmHg had better physical performance than patients with
      lower blood pressure in the normotensive range. The risk-benefit tradeoff of
      aggressive blood pressure control, particularly in low-functioning patients,
      should be reexamined.

PMID- 25399254
TI  - GRP78 regulates sensitivity of human colorectal cancer cells to DNA targeting
      agents.
AB  - This study was carried out to investigate the activation status of unfolded
      protein response (UPR) in colorectal cancer (CRC) and its contribution to CRC
      resistance to chemotherapy-induced apoptosis. Chemotherapy-induced apoptosis was
      assessed by the propidium iodide method. Activation of UPR was evaluated in CRC
      cell lines using immunoblotting technique and in CRC tissues using
      immunohistochemistry. Findings of the present study revealed that the UPR is
      constitutively activated in CRC cell lines and CRC tissues isolated from
      patients, as evidenced by relatively high levels of the 78-kDa glucose-regulated
      protein (GRP78) and spliced X-box-binding protein 1 mRNA in tissue samples. In
      addition, CRC cell lines differentially responded to clinically relevant DNA
      targeting agents including cisplatin, and 5-flourouracil. Moreover, the levels of
      GRP78 were inversely associated with sensitivity of CRC cells to chemotherapy
      induced apoptosis. Inhibition of GRP78 by siRNA resulted in increased sensitivity
      of CRC cells to chemotherapeutic agents. Collectively, current results appear to
      provide novel insights into the role of UPR in determining sensitivity of CRC
      cells to chemotherapeutic agents and might have important implications for
      personalized CRC treatment. 

PMID- 25399258
TI  - Pictorial quilt: Harriet Powers.

PMID- 25399255
TI  - A network biology workflow to study transcriptomics data of the diabetic liver.
AB  - BACKGROUND: Nowadays a broad collection of transcriptomics data is publicly
      available in online repositories. Methods for analyzing these data often aim at
      deciphering the influence of gene expression at the process level. Biological
      pathway diagrams depict known processes and capture the interactions of gene
      products and metabolites, information that is essential for the computational
      analysis and interpretation of transcriptomics data.The present study describes a
      comprehensive network biology workflow that integrates differential gene
      expression in the human diabetic liver with pathway information by building a
      network of interconnected pathways. Worldwide, the incidence of type 2 diabetes
      mellitus is increasing dramatically, and to better understand this multifactorial
      disease, more insight into the concerted action of the disease-related processes
      is needed. The liver is a key player in metabolic diseases and diabetic patients
      often develop non-alcoholic fatty liver disease. RESULTS: A publicly available
      dataset comparing the liver transcriptome from lean and healthy vs. obese and
      insulin-resistant subjects was selected after a thorough analysis. Pathway
      analysis revealed seven significantly altered pathways in the WikiPathways human
      pathway collection. These pathways were then merged into one combined network
      with 408 gene products, 38 metabolites and 5 pathway nodes. Further analysis
      highlighted 17 nodes present in multiple pathways, and revealed the connections
      between different pathways in the network. The integration of transcription
      factor-gene interactions from the ENCODE project identified new links between the
      pathways on a regulatory level. The extension of the network with known drug
      target interactions from DrugBank allows for a more complete study of drug
      actions and helps with the identification of other drugs that target proteins up-
      or downstream which might interfere with the action or efficiency of a drug.
      CONCLUSIONS: The described network biology workflow uses state-of-the-art pathway
      and network analysis methods to study the rewiring of the diabetic liver. The
      integration of experimental data and knowledge on disease-affected biological
      pathways, including regulatory elements like transcription factors or drugs,
      leads to improved insights and a clearer illustration of the overall process. It
      also provides a resource for building new hypotheses for further follow-up
      studies. The approach is highly generic and can be applied in different research
      fields.

PMID- 25399259
TI  - Clinical trial results may lead to changes in cardiovascular care.

PMID- 25399260
TI  - The unintended consequences of the "observation status" policy.

PMID- 25399267
TI  - Population and personalized medicine in the modern era.

PMID- 25399268
TI  - Elimination of lipid levels from quality measures: implications and alternatives.

PMID- 25399269
TI  - Patients with undiagnosed hypertension: hiding in plain sight.

PMID- 25399270
TI  - A piece of my mind. N of 1.

PMID- 25399271
TI  - Searching for treatments of heart failure with preserved ejection fraction:
      matching the data to the question.

PMID- 25399272
TI  - Progress against cardiovascular disease: putting the pieces together.

PMID- 25399273
TI  - Comparison of vascular closure devices vs manual compression after femoral artery
      puncture: the ISAR-CLOSURE randomized clinical trial.
AB  - IMPORTANCE: The role of vascular closure devices (VCD) for the achievement of
      hemostasis in patients undergoing transfemoral coronary angiography remains
      controversial. OBJECTIVE: To compare outcomes with the use of 2 hemostasis
      strategies after diagnostic coronary angiography performed via transfemoral
      access-a VCD-based strategy with 2 types of devices, an intravascular device and
      an extravascular device, vs standard manual compression. The primary hypothesis
      to be tested was that femoral hemostasis achieved through VCD is noninferior to
      manual compression in terms of vascular access-site complications. A secondary
      objective was the comparison of the 2 types of VCD. DESIGN, SETTING, AND
      PARTICIPANTS: Randomized, large-scale, multicenter, open-label clinical trial. We
      enrolled 4524 patients undergoing coronary angiography with a 6 French sheath via
      the common femoral artery from April 2011 through May 2014 in 4 centers in
      Germany. Last 30-day follow-up was performed in July 2014. INTERVENTIONS: After
      angiography of the access site, patients were randomized to hemostasis with an
      intravascular VCD, extravascular VCD, or manual compression in a 1:1:1 ratio.
      MAIN OUTCOMES AND MEASURES: Primary end point: the composite of access site
      related vascular complications at 30 days after randomization with a 2%
      noninferiority margin. Secondary end points: time to hemostasis, repeat manual
      compression, and VCD failure. An alpha-level of .025 was chosen for primary and
      secondary comparisons. RESULTS: Of the 4524 enrolled patients, 3015 were randomly
      assigned to a VCD group (1509 received intravascular VCD and 1506 received
      extravascular VCD) and 1509 patients were randomly assigned to the manual
      compression group. Before hospital discharge, duplex sonography of the access
      site was performed in 4231 (94%) patients. The primary end point was observed in
      208 patients (6.9%) assigned to receive a VCD and 119 patients (7.9%) assigned to
      manual compression (difference, -1.0% [1-sided 97.5% CI, 0.7%]; P for
      noninferiority<.001). Time to hemostasis was significantly shorter in patients
      with VCD (1 minute [interquartile range {IQR}, 0.5-2.0]), vs manual compression
      (10 minutes [IQR, 10-15]; P < .001). Time to hemostasis was significantly shorter
      among patients with intravascular VCD (0.5 minute [IQR, 0.2-1.0]), vs
      extravascular VCD (2.0 minutes [IQR, 1.0-2.0]; P <.001) and closure device
      failure was also significantly lower among those with intravascular vs
      extravascular VCD (80 patients [5.3%], vs 184 patients [12.2%]; P < .001).
      CONCLUSIONS AND RELEVANCE: In patients undergoing transfemoral coronary
      angiography, VCDs were noninferior to manual compression in terms of vascular
      access-site complications and reduced time to hemostasis. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01389375.

PMID- 25399275
TI  - Association of inpatient vs outpatient onset of ST-elevation myocardial
      infarction with treatment and clinical outcomes.
AB  - IMPORTANCE: Reperfusion times for ST-elevation myocardial infarction (STEMI)
      occurring in outpatients have improved significantly, but quality improvement
      efforts have largely ignored STEMI occurring in hospitalized patients (inpatient
      onset STEMI). OBJECTIVE: To define the incidence and variables associated with
      treatment and outcomes of patients who develop STEMI during hospitalization for
      conditions other than acute coronary syndromes (ACS). DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective observational analysis of STEMIs occurring between
      2008 and 2011 as identified in the California State Inpatient Database.
      EXPOSURES: STEMIs were classified as inpatient onset or outpatient onset based on
      present-on-admission codes. Patients who had a STEMI after being hospitalized for
      ACS were excluded from the analysis. MAIN OUTCOMES AND MEASURES: Regression
      models were used to evaluate associations among location of onset of STEMI,
      resource utilization, and outcomes. Adjustments were made for patient age, sex,
      comorbidities, and hospital characteristics. The analysis allowed for the
      location of inpatient STEMI to have a multiplicative rather than an additive
      effect for resource utilization since these measures were highly skewed. RESULTS:
      A total of 62,021 STEMIs were identified in 303 hospitals, of which 3068 (4.9%)
      occurred in patients hospitalized for non-ACS indications. Patients with
      inpatient-onset STEMI were older (mean, 71.5 [SD, 13.5] years vs 64.9 [SD, 14.1]
      years; P < .001) and more frequently female (47.4% vs 32%; P < .001) than those
      with outpatient-onset STEMI. Patients with inpatient-onset STEMI had higher in
      hospital mortality (33.6% vs 9.2%; adjusted odds ratio (AOR), 3.05; 95% CI, 2.76
      3.38; P < .001), were less likely to be discharged home (33.7% vs 69.4%; AOR,
      0.38; 95% CI, 0.34-0.42; P < .001), and were less likely to undergo cardiac
      catheterization (33.8% vs 77.8%; AOR, 0.19; 95% CI, 0.16-0.21; P < .001) or
      percutaneous coronary intervention (21.6% vs 65%; AOR, 0.23; 95% CI, 0.21-0.26; P
      < .001). Length of stay and inpatient charges were higher for inpatient-onset
      STEMI (mean length of stay, 13.4 days [95% CI, 12.8-14.0 days] vs 4.7 days [95%
      CI, 4.6-4.8 days]; adjusted multiplicative effect, 2.51; 95% CI, 2.35-2.69; P <
      .001; mean inpatient charges, $245,000 [95% CI, $235,300-$254,800] vs $129,000
      [95% CI, $127,900-$130,100]; adjusted multiplicative effect, 2.09; 95% CI, 1.93
      2.28; P < .001). CONCLUSIONS AND RELEVANCE: Patients who had a STEMI while
      hospitalized for a non-ACS condition, compared with those with onset of STEMI as
      an outpatient, were less likely to undergo invasive testing or intervention and
      had a higher in-hospital mortality rate.

PMID- 25399274
TI  - Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a
      randomized clinical trial.
AB  - IMPORTANCE: While effective in preventing stroke in patients with atrial
      fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need
      for lifelong coagulation monitoring, and multiple drug and diet interactions.
      OBJECTIVE: To determine whether a local strategy of mechanical left atrial
      appendage (LAA) closure was noninferior to warfarin. DESIGN, SETTING, AND
      PARTICIPANTS: PROTECT AF was a multicenter, randomized (2:1), unblinded, Bayesian
      designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and
      at least 1 additional stroke risk factor (CHADS2 score >=1). Enrollment occurred
      between February 2005 and June 2008 and included 4-year follow-up through October
      2012. Noninferiority required a posterior probability greater than 97.5% and
      superiority a probability of 95% or greater; the noninferiority margin was a rate
      ratio of 2.0 comparing event rates between treatment groups. INTERVENTIONS: Left
      atrial appendage closure with the device (n = 463) or warfarin (n = 244; target
      international normalized ratio, 2-3). MAIN OUTCOMES AND MEASURES: A composite
      efficacy end point including stroke, systemic embolism, and
      cardiovascular/unexplained death, analyzed by intention-to-treat. RESULTS: At a
      mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events
      among 463 patients (8.4%) in the device group for a primary event rate of 2.3
      events per 100 patient-years, compared with 34 events among 244 patients (13.9%)
      for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate
      ratio, 0.60; 95% credible interval, 0.41-1.05), meeting prespecified criteria for
      both noninferiority (posterior probability, >99.9%) and superiority (posterior
      probability, 96.0%). Patients in the device group demonstrated lower rates of
      both cardiovascular mortality (1.0 events per 100 patient-years for the device
      group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin
      [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95% CI, 0.21-0.75; P = .005)
      and all-cause mortality (3.2 events per 100 patient-years for the device group
      [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin
      [44/244 patients, 18.0%]; HR, 0.66; 95% CI, 0.45-0.98; P = .04). CONCLUSIONS AND
      RELEVANCE: After 3.8 years of follow-up among patients with nonvalvular AF at
      elevated risk for stroke, percutaneous LAA closure met criteria for both
      noninferiority and superiority, compared with warfarin, for preventing the
      combined outcome of stroke, systemic embolism, and cardiovascular death, as well
      as superiority for cardiovascular and all-cause mortality. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00129545.

PMID- 25399276
TI  - Association between use of beta-blockers and outcomes in patients with heart
      failure and preserved ejection fraction.
AB  - IMPORTANCE: Heart failure with preserved ejection fraction (HFPEF) may be as
      common and may have similar mortality as heart failure with reduced ejection
      fraction (HFREF). beta-Blockers reduce mortality in HFREF but are inadequately
      studied in HFPEF. OBJECTIVE: To test the hypothesis that beta-blockers are
      associated with reduced all-cause mortality in HFPEF. DESIGN: Propensity score
      matched cohort study using the Swedish Heart Failure Registry. Propensity scores
      for beta-blocker use were derived from 52 baseline clinical and socioeconomic
      variables. SETTING: Nationwide registry of 67 hospitals with inpatient and
      outpatient units and 95 outpatient primary care clinics in Sweden with patients
      entered into the registry between July 1, 2005, and December 30, 2012, and
      followed up until December 31, 2012. PARTICIPANTS: From a consecutive sample of
      41,976 patients, 19,083 patients with HFPEF (mean [SD] age, 76 [12] years; 46%
      women). Of these, 8244 were matched 2:1 based on age and propensity score for
      beta-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF.
      Also we conducted a positive-control consistency analysis involving 22,893
      patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027
      untreated patients. EXPOSURES: beta-Blockers prescribed at discharge from the
      hospital or during an outpatient visit, analyzed 2 ways: without consideration of
      crossover and per-protocol analysis with censoring at crossover, if applicable.
      MAIN OUTCOMES AND MEASURES: The prespecified primary outcome was all-cause
      mortality and the secondary outcome was combined all-cause mortality or heart
      failure hospitalization. RESULTS: Median follow-up in HFPEF was 755 days,
      overall; 709 days in the matched cohort; no patients were lost to follow-up. In
      the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated
      patients, and 5-year survival was 45% vs 42%, with 2279 (41%) vs 1244 (45%) total
      deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95%
      CI, 0.86-0.996; P = .04). beta-Blockers were not associated with reduced combined
      mortality or heart failure hospitalizations: 3368 (61%) vs 1753 (64%) total for
      first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95%
      CI, 0.92-1.04; P = .46). In the matched HFREF cohort, beta-blockers were
      associated with reduced mortality (HR, 0.89; 95% CI, 0.82-0.97, P=.005) and also
      with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95%
      CI, 0.84-0.95; P = .001). CONCLUSIONS AND RELEVANCE: In patients with HFPEF, use
      of beta-blockers was associated with lower all-cause mortality but not with
      combined all-cause mortality or heart failure hospitalization. beta-Blockers in
      HFPEF should be examined in a large randomized clinical trial.

PMID- 25399277
TI  - Extent, location, and clinical significance of non-infarct-related coronary
      artery disease among patients with ST-elevation myocardial infarction.
AB  - IMPORTANCE: Little information exists about the anatomical characteristics and
      clinical relevance of non-infarct-related artery (IRA) disease among patients
      with ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: To
      investigate the incidence, extent, and location of obstructive non-IRA disease
      and compare 30-day mortality according to the presence of non-IRA disease in
      patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of
      patients pooled from a convenience sample of 8 independent, international,
      randomized STEMI clinical trials published between 1993 and 2007. Follow-up
      varied from 1 month to 1 year. Among 68,765 patients enrolled in the trials,
      28,282 patients with valid angiographic information were included in this
      analysis. Obstructive coronary artery disease was defined as stenosis of 50% or
      more of the diameter of a major epicardial artery. To assess the generalizability
      of trial-based results, external validation was performed using observational
      data for patients with STEMI from the Korea Acute Myocardial Infarction Registry
      (KAMIR) (between November 1, 2005, and December 31, 2013; n = 18,217) and the
      Duke Cardiovascular Databank (between January 1, 2005, and December 31, 2012; n =
      1812). MAIN OUTCOMES AND MEASURES: Thirty-day mortality following STEMI. RESULTS:
      Overall, 52.8% (14,929 patients) had obstructive non-IRA disease; 29.6% involved
      1 vessel and 18.8% involved 2 vessels. There was no substantial difference in the
      extent and distribution of non-IRA disease according to the IRA territory.
      Unadjusted and adjusted rates of 30-day mortality were significantly higher in
      patients with non-IRA disease than in those without non-IRA disease (unadjusted,
      4.3% vs 1.7%, respectively; risk difference, 2.7% [95% CI, 2.3% to 3.0%], P <
      .001; and adjusted, 3.3% vs 1.9%, respectively; risk difference, 1.4% [95% CI,
      1.0% to 1.8%], P < .001). The overall prevalence and association of non-IRA
      disease with 30-day mortality was consistent with findings from the KAMIR
      registry (adjusted, 3.6% for patients with non-IRA disease vs 2.5% in those
      without it; risk difference, 1.1% [95% CI, 0.6% to 1.7%]; P < .001), but not with
      the Duke database (adjusted, 4.7% with non-IRA disease vs 4.3% without it; risk
      difference, 0.4% [95% CI, -1.4% to 2.2%], P = .65). CONCLUSIONS AND RELEVANCE: In
      a retrospective pooled analysis of 8 clinical trials, obstructive non-IRA disease
      was common among patients presenting with STEMI, and was associated with a modest
      statistically significant increase in 30-day mortality. These findings require
      confirmation in prospectively designed studies, but raise questions about the
      appropriateness and timing of non-IRA revascularization in patients with STEMI.

PMID- 25399278
TI  - Revascularization in stable coronary artery disease.

PMID- 25399279
TI  - Fixed-dose combination therapy (polypill) for the prevention of cardiovascular
      disease.
AB  - CLINICAL QUESTION: Is fixed-dose combination therapy (polypill) that combines
      antiplatelet, blood pressure-lowering, and cholesterol-lowering medications into
      a single pill associated with improved cardiovascular disease (CVD) risk factors
      or reduced all-cause mortality or fatal and nonfatal CVD events? Is the polypill
      associated with an increase in adverse events? BOTTOM LINE: Polypills are
      associated with greater reductions in systolic blood pressure and total
      cholesterol compared with usual care, placebo, or active comparators, but also
      with a 19% higher risk of any adverse event. Due to limited power from available
      evidence, the association of polypills with all-cause mortality or fatal and
      nonfatal CVD events is uncertain.

PMID- 25399280
TI  - Acute troponin elevation and the classification of myocardial infarction.

PMID- 25399281
TI  - Trends in mortality rates by subtypes of heart disease in the United States, 2000
      2010.

PMID- 25399282
TI  - Follow-up from childhood to adulthood of individuals with family history of
      Brugada syndrome and normal electrocardiograms.

PMID- 25399283
TI  - Red blood cell transfusion strategies and health care-associated infection.

PMID- 25399284
TI  - Red blood cell transfusion strategies and health care-associated infection.

PMID- 25399285
TI  - Red blood cell transfusion strategies and health care-associated infection-
      reply.

PMID- 25399286
TI  - Treatment for patients at intermediate risk of a common duct stone.

PMID- 25399287
TI  - Treatment for patients at intermediate risk of a common duct stone--reply.

PMID- 25399288
TI  - Drugs for macular degeneration.

PMID- 25399292
TI  - Drugs for macular degeneration--reply.

PMID- 25399294
TI  - Gaskell and the physiology of the heart.

PMID- 25399295
TI  - JAMA patient page. Transcatheter aortic valve replacement.

PMID- 25399296
TI  - Lhx3 is required to maintain cancer cell development of high-grade
      oligodendroglioma.
AB  - The LHX genes play a substantial role in an amount of adorning processes.
      Potential roles of LHXs have been accepted and approved in an assortment of
      neoplastic tissues as bump suppressors or promoters depending on bump cachet and
      types. The aim of this abstraction was to investigate the action role of LHXs in
      the animal High-grade Oligodendroglioma (HG-OT). The gene announcement changes of
      LHXs in HG-OT tissues compared with non-cancerous colorectal tissues were
      detected using application real-time quantitative about-face transcriptase
      polymerase alternation acknowledgment (QRT-PCR) assay and immunohistochemistry.
      And we articulate the gene LHX3 that was decidedly up-regulated in HG-OT by QRT
      PCR assay and immunohistochemistry. Furthermore, it was obvious that LHX3
      responds to blight corpuscle admeasurement in vitro and LHX3 announcement
      activated with animated beta-catenin levels in HG-OT and beta-catenin action was
      appropriate for LHX3's oncogenic effects.  Mechanistically, LHX3 facilitates TCF4
      to bind to beta-catenin and facilitates LHX3/TCF4/beta-catenin circuitous and
      trans-active it's after ambition gene. LHX3 mutations that agitate the LHX3-beta
      catenin alternation partially anticipate its action in bump cells. All in all,
      LHX3 is a frequently activated bump apostle that actuates Wnt/beta-catenin
      signaling in blight beef of HG-OT. 

PMID- 25399297
TI  - Tannic acid mitigates the DMBA/croton oil-induced skin cancer progression in
      mice.
AB  - Skin cancer is the most common malignancy in the world and also one of the major
      causes of death worldwide. The toxic environmental pollutant 7,12
      dimethylbenz[a]anthracene (DMBA) is a skin-specific carcinogen. Tannic acid (TA)
      is reported to be effective against various types of chemical-induced toxicities
      and carcinogenesis as well. In the present study, we have evaluated the
      therapeutic potential of tannic acid in DMBA + croton oil-induced skin cancer in
      Swiss albino mice. Protective effect of TA against skin cancer was evaluated in
      terms of antioxidant enzymes activities, lipid peroxidation, histopathological
      changes and expression of inflammation and early tumour markers. DMBA + croton
      oil causes depletion of antioxidant enzymes (p < 0.001) and elevation of early
      inflammatory and tumour promotional events. TA prevents the DMBA + croton oil
      induced toxicity through a protective mechanism that involves the reduction of
      oxidative stress as well as COX-2, i-NOS, PCNA protein expression and level of
      proinflammatory cytokine such as IL-6 release at a very significant level (p <
      0.001). It could be concluded from our results that TA attenuates DMBA + croton
      oil-induced tumour promotional potential possibly by inhibiting oxidative and
      inflammatory responses and acts as antioxidant, anti-inflammatory and
      antiproliferative agent. 

PMID- 25399300
TI  - Bone cell mechanosensation of fluid flow stimulation: a fluid-structure
      interaction model characterising the role integrin attachments and primary cilia.
AB  - Load-induced fluid flow acts as an important biophysical signal for bone cell
      mechanotransduction in vivo, where the mechanical environment is thought to be
      monitored by integrin and primary cilia mechanoreceptors on the cell body.
      However, precisely how integrin- and primary cilia-based mechanosensors interact
      with the surrounding fluid flow stimulus and ultimately contribute to the
      biochemical response of bone cells within either the in vitro or in vivo
      environment remains poorly understood. In this study, we developed fluid
      structure interaction models to characterise the deformation of integrin- and
      primary cilia-based mechanosensors in bone cells under fluid flow stimulation.
      Under in vitro fluid flow stimulation, these models predicted that integrin
      attachments on the cell-substrate interface were highly stimulated epsilon(eq) >
      200,000 MUepsilon, while the presence of a primary cilium on the cell also
      resulted in significant strain amplifications, arising at the ciliary base. As
      such, these mechanosensors likely play a role in mediating bone
      mechanotransduction in vitro. Under in vivo fluid flow stimulation, integrin
      attachments along the canalicular wall were highly stimulated and likely play a
      role in mediating cellular responses in vivo. The role of the primary cilium as a
      flow sensor in vivo depended upon its configuration within the lacunar cavity.
      Specifically, our results showed that a short free-standing primary cilium could
      not effectively fulfil a flow sensing role in vivo. However, a primary cilium
      that discretely attaches the lacunar wall can be highly stimulated, due to
      hydrodynamic pressure in the lacunocanalicular system and, as such, could play a
      role in mediating bone mechanotransduction in vivo.

PMID- 25399299
TI  - Impact of domestication in the production of the class II lanthipeptide
      lichenicidin by Bacillus licheniformis I89.
AB  - Investigation on lantibiotics biosynthesis constitutes an emergent field, since
      these molecules have demonstrated a great potential to replace the so-called
      "traditional antibiotics". The adaptation of bacteria to laboratory conditions
      (domestication) is an unpredictable phenomenon, which sometimes is associated
      with the loss of important biotechnological properties. In this study, the
      domestication of Bacillus licheniformis was associated with the production of the
      lantibiotic lichenicidin, a two-peptide lantibiotic with activity against several
      Gram-positive bacteria. 

PMID- 25399298
TI  - Cross-talk between p(38)MAPK and G ialpha in regulating cPLA 2 activity by ET-1
      in pulmonary smooth muscle cells.
AB  - Endothelin-1 (ET-1) is known as the most potent vasoconstrictor yet described.
      Infusion of ET-1 into isolated rabbit lung has been shown to cause pulmonary
      vasoconstriction with the involvement of arachidonic acid metabolites. Given the
      potency of arachidonic acid metabolites, the activity of phospholipase A2 must be
      tightly regulated. Herein, we determined the mechanisms by which ET-1 stimulates
      cPLA2 activity during ET-1 stimulation of bovine pulmonary artery smooth muscle
      cells. We demonstrated that (i) treatment of bovine pulmonary artery smooth
      muscle cells with ET-1 stimulates cPLA2 activity in the cell membrane; (ii) ET-1
      caused increase in O 2 (.-) production occurs via NADPH oxidase-dependent
      mechanism; (iii) ET-1-stimulated NADPH oxidase activity is markedly prevented
      upon pretreatment with PKC-zeta inhibitor, indicating that PKC-zeta plays a
      prominent role in this scenario; (iv) ET-1-induced NADPH oxidase-derived O 2 (.-)
      stimulates an aprotinin sensitive protease activity due to prominent increase in
      [Ca(2+)]i; (v) the aprotinin sensitive protease plays a pivotal role in
      activating PKC-alpha, which in turn phosphorylates p(38)MAPK and subsequently
      Gialpha leading to the activation of cPLA2. Taken together, we suggest that cross
      talk between p(38)MAPK and Gialpha with the involvement of PKC-zeta, NADPH
      oxidase-derived O 2 (.-) , [Ca(2+)]i, aprotinin-sensitive protease and PKC-alpha
      play a pivotal role for full activation of cPLA2 during ET-1 stimulation of
      pulmonary artery smooth muscle cells. 

PMID- 25399301
TI  - TGF-beta1, Ghrelin, Neurexin, and Neuroligin are predictive biomarkers for
      postoperative prognosis of laparoscopic surgery in children with Hirschsprung
      disease.
AB  - The study was set to analyze the predictive values of transforming growth factor
      beta1 (TGF-beta1), Ghrelin, Neurexin, and Neuroligin protein expression on
      postoperative prognosis of laparoscopic surgery in children with Hirschsprung
      disease. 281 cases of children with Hirschsprung disease, admitted into Guangdong
      Women and Children Hospital and Guangzhou women and children's medical center
      from March 2009 to March 2014, were treated with laparoscopic radical surgery for
      Hirschsprung disease. They were divided into the good and the poor prognosis
      groups according to their recuperation and complications. Protein expressions of
      TGF-beta1, Ghrelin, Neurexin, and Neuroligin were prospectively analyzed. The
      correlations between the expressions of these proteins and the prognosis were
      analyzed. There were 129 cases of children with poor prognosis, accounting for
      45.9 %. There were no significant differences in the expressions of TGF-beta1
      mRNA and proteins within the group in both the groups (p > 0.05). TGF-beta1 mRNA
      and protein expressions of the poor prognosis group were significantly higher
      than those of the good prognosis group in each segment of intestine (p < 0.05).
      Protein detection results manifested that Ghrelin protein expression gradually
      increased along narrow segment, transitional segment, and expansion segment in
      both groups. Ghrelin protein expression of the poor prognosis group was
      significantly lower than that of the good prognosis group in each segment of
      intestine (p < 0.05). There were significant differences in the protein
      expressions of Neurexin and Neuroligin within the group. The protein expressions
      of Neurexin and Neuroligin in expansion segment were the highest. Neurexin and
      Neuroligin protein expressions of the poor prognosis group were significantly
      lower than those of the good prognosis group in each segment of intestine (p <
      0.05). Increasing expression of TGF-beta1 protein, decreasing expressions of
      Ghrelin, Neurexin, and Neuroligin proteins can induce the loss or dysfunction of
      ganglion cells in distal intestinal canal, which is closely correlated with the
      occurrences of adverse prognosis, such as increased intestinal peristalsis
      recovery time, increased complication rate etc., in children. It has a high value
      for predicting prognosis of children patients with Hirschsprung disease after
      surgical intervention.

PMID- 25399302
TI  - Cytoskeletal Alterations and Biomechanical Properties of parkin-Mutant Human
      Primary Fibroblasts.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative diseases.
      Genes which have been implicated in autosomal-recessive PD include PARK2 which
      codes for parkin, an E3 ubiquitin ligase that participates in a variety of
      cellular activities. In this study, we compared parkin-mutant primary
      fibroblasts, from a patient with parkin compound heterozygous mutations, to
      healthy control cells. Western blot analysis of proteins obtained from patient's
      fibroblasts showed quantitative differences of many proteins involved in the
      cytoskeleton organization with respect to control cells. These molecular
      alterations are accompanied by changes in the organization of actin stress fibers
      and biomechanical properties, as revealed by confocal laser scanning microscopy
      and atomic force microscopy. In particular, parkin deficiency is associated with
      a significant increase of Young's modulus of null-cells in comparison to normal
      fibroblasts. The current study proposes that parkin influences the spatial
      organization of actin filaments, the shape of human fibroblasts, and their
      elastic response to an external applied force. 

PMID- 25399303
TI  - Effects of Novel Dinuclear Cisplatinum(II) Complexes on the Electrical Properties
      of Human Molt-4 Leukemia Cells.
AB  - The aim of this study was to determine the influence of cisplatin and novel
      dinuclear platinum(II) complexes on the membrane electrical properties and lipid
      peroxidation levels of the Molt-4 human leukemia cell line. Changes in cell
      function may affect the basal electrical surface properties of cell membranes.
      These changes can be detected using electrokinetic measurements. Surface charge
      densities of Molt-4 cells were measured as a function of pH. A four-component
      equilibrium model was used to describe the interaction between the ions in
      solution and on cell membrane surfaces. Agreement was found between the
      experimental and theoretical charge variation curves of the leukemia cells at pH
      2.5-9. Lipid peroxidation was estimated by measuring levels of 8-iso
      prostaglandine F2alpha [isoprostanes]. Acid and base functional group
      concentrations and average association constants with hydroxyl ions were smaller
      in cisplatin- or dinuclear platinum(II) complex-treated leukemia cell membranes
      compared to those in untreated cancer cells, and the average association
      constants with hydrogen ions were higher. Levels of lipid peroxidation products
      in cisplatin- or dinuclear platinum(II) complex-treated leukemia cell were higher
      than those found in untreated cancer cells. 

PMID- 25399304
TI  - Safety of balloon kyphoplasty in the treatment of osteoporotic vertebral
      compression fractures in Europe: a meta-analysis of randomized controlled trials.
AB  - PURPOSE: The study aims to evaluate the safety of balloon kyphoplasty in the
      treatment of painful osteoporotic vertebral compression fractures in Europe.
      METHODS: Systematic review of the literature, until September 2013, and meta
      analysis of randomized controlled trials performed in Europe assessing the safety
      of balloon kyphoplasty in patients with symptomatic osteoporotic vertebral
      fractures. Outcomes sought include cement leaks, serious clinical complications
      and new vertebral fractures. RESULTS: Six randomized controlled trials fulfilled
      the inclusion criteria. These studies included data on 525 treated levels in 424
      patients. Cement leakages were detected in 18.3 % (95 % CI 11.6, 23.0) of
      fractures intervened. In about 0.5 % (95 % CI 0.1, 1.1) of fractures leakages
      proved to be symptomatic. Serious clinical complications were recorded in 11.5 %
      (95 % CI 1.1, 21.7) of patients treated with balloon kyphoplasty with several of
      these cases requiring intensive treatment or postoperative surgery. New vertebral
      fractures were detected in 20.7 % (95 % CI 0.4, 40.9) of patients treated but
      rates showed an upward pattern when the follow-up period increased. In 54 % of
      such cases, the fractures were located in regions adjacent to the treated level.
      CONCLUSIONS: The safety profile and associated complications of balloon
      kyphoplasty shown in this analysis, based on the evidence provided by existing
      randomized controlled trials, can be of help to the practicing clinician who must
      contrast them with the potential benefits of the technique. These data represent
      an important step towards a balanced evaluation of the intervention though, a
      better reporting and more reliable data on long-term assessment of potential
      sequelae are needed.

PMID- 25399305
TI  - Comments on stapled anopexy and STARR in surgical treatment of haemorrhoidal
      disease.

PMID- 25399306
TI  - Therapeutic effect of Jinlongshe Granule () on quality of life of stage IV
      gastric cancer patients using EORTC QLQ-C30: A double-blind placebo-controlled
      clinical trial.
AB  - OBJECTIVE: To evaluate the impact of Jinlongshe Granule (, JLSG) on quality of
      life (QOL) of stage IV gastric cancer patients. METHODS: This randomized, double
      blind and placebo-controlled clinical trial included 50 patients with advanced
      gastric cancer. They were equally randomized into a JLSG group and a placebo
      group. Patients in both groups received routine Chinese herbal decoctions
      according to Chinese medicine (CM) treatment based on syndrome differentiation.
      Patients in JLSG group received additional JLSG, and those in the placebo group
      received an additional placebo. In the JLSG group, 19 patients who completed the
      study were used for analysis. In the placebo group, finally the data of 20
      patients who completed the study were used for analysis. The treatment course was
      at least 3 months, and the follow-up duration was at least 6 months in 5
      interviews. Repeated measurements of the subscale items and individual items in
      European Organization for Research and Treatment of Cancer Core Quality of Life
      Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared
      using different patient groups, changes over time and changes within one group
      over time independently to observe the tendency of changes in the scores.
      RESULTS: Using time as the variant, there was signifificant difference in 4
      functional scales (physical, role, emotional and social, P<0.05), 3 symptom
      scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health
      status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia
      (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and
      financial difficulties (P<0.05). There was also signifificant difference in these
      items between the two groups when the placebo group and group over time were used
      as variants (P<0.05 or P<0.01). CONCLUSION: Additional use of JLSG on the basis
      of routine CM treatment could improve the somatic function, role function,
      emotional function, social function, cognitive function and general QOL of
      patients with advanced gastric cancer, and relieve the symptoms of fatigue,
      nausea and vomiting, pain, loss of appetite and constipation.

PMID- 25399307
TI  - Antipyretic and anti-asthmatic activities of traditional Chinese herb-pairs,
      Ephedra and Gypsum.
AB  - OBJECTIVE: Mahuang-Shigao herb-pair is a famous formula composed of Ephedra and
      Gypsum. The herb-pair is frequently used for treating cold symptoms and bronchial
      asthma in the clinical practice of Chinese medicine (CM). In the present study,
      we evaluated evidence for the benefit of combined use of Ephedra and Gypsum by
      analyzing the antipyretic and anti-asthmatic activities of Ephedra-Gypsum.
      METHODS: The antipyretic effects of Ephedra-Gypsum were evaluated in yeast
      induced hyperthermia test. Thirty male Wistar rats were randomly divided into 5
      groups, including control group, standard aspirin group, and 3 Ephedra- Gypsum
      groups of different doses (6, 12, 24 g/kg). Ephedra-Gypsum extract and asprin
      were administered orally 6 h after the injection of yeast solution and body
      temperature was measured every 1 h for 8 h. The antiasthmatic effects of Ephedra
      Gypsum were evaluated using an ovalbumin (OVA)-induced asthmatic rat model.
      Thirty-six male SD rats were randomly divided into 6 groups. Rats were
      alternately sensitized and OVA+Al(OH) challenged by exposure to mists of
      ovalbumin. Ephedra-Gypsum extracts (6, 12, 24 g/kg) or dexamethasone were
      administered 45 min prior to the allergen challenge for 8 days. Latent period and
      the weight of wet to dry ratio of lung were determined. In addition, the
      eosinophils in blood and white blood cell (WBC) were counted by an YZ-Hemavet
      Analyzer. RESULTS: The Ephedra-Gypsum extracts at test dose (6, 12, 24 g/kg)
      significantly and dose-dependently attenuated yeast-induced fever in rats. The
      Ephedra-Gypsum extracts also prolonged the latent period, reduced OVA-induced
      increases in eosinophils and WBC, and decreased the wet and dry weight ratio of
      the lungs in the anti-asthmatic test. CONCLUSIONS: These findings indicate that
      the Ephedra-Gypsum extract has antipyretic and anti-asthmatic properties. Hence,
      the results support additional scientific evidence in prescriptions.

PMID- 25399308
TI  - Experimental evolution of a green fluorescent protein composed of 19 unique amino
      acids without tryptophan.
AB  - At some stage of evolution, genes of organisms may have encoded proteins that
      were synthesized using fewer than 20 unique amino acids. Similar to evolution of
      the natural 19-amino-acid proteins GroEL/ES, proteins composed of 19 unique amino
      acids would have been able to evolve by accumulating beneficial mutations within
      the 19-amino-acid repertoire encoded in an ancestral genetic code. Because Trp is
      thought to be the last amino acid included in the canonical 20-amino-acid
      repertoire, this late stage of protein evolution could be mimicked by
      experimental evolution of 19-amino-acid proteins without tryptophan (Trp). To
      further understand the evolution of proteins, we tried to mimic the evolution of
      a 19-amino-acid protein involving the accumulation of beneficial mutations using
      directed evolution by random mutagenesis on the whole targeted gene sequence. We
      created active 19-amino-acid green fluorescent proteins (GFPs) without Trp from a
      poorly fluorescent 19-amino-acid mutant, S1-W57F, by using directed evolution
      with two rounds of mutagenesis and selection. The N105I and S205T mutations
      showed beneficial effects on the S1-W57F mutant. When these two mutations were
      combined on S1-W57F, we observed an additive effect on the fluorescence
      intensity. In contrast, these mutations showed no clear improvement individually
      or in combination on GFPS1, which is the parental GFP mutant composed of 20 amino
      acids. Our results provide an additional example for the experimental evolution
      of 19-amino-acid proteins without Trp, and would help understand the mechanisms
      underlying the evolution of 19-amino-acid proteins. (236 words). 

PMID- 25399310
TI  - Thermophilic fungi in the new age of fungal taxonomy.
AB  - Thermophilic fungi are of wide interest due to their potential to produce heat
      tolerant enzymes for biotechnological processes. However, the taxonomy of such
      organisms remains obscure, especially given new developments in the nomenclature
      of fungi. Here, we examine the taxonomy of the thermophilic fungi most commonly
      used in industry in light of the recent taxonomic changes following the adoption
      of the International Code of Nomenclature for Algae, Fungi and Plants and also
      based on the movement One Fungus = One Name. Despite the widespread use of these
      fungi in applied research, several thermotolerant fungi still remain classified
      as thermophiles. Furthermore, we found that while some thermophilic fungi have
      had their genomes sequenced, many taxa still do not have barcode sequences of
      reference strains available in public databases. This lack of basic information
      is a limiting factor for the species identification of thermophilic fungi and for
      metagenomic studies in this field. Based on next-generation sequencing, such
      studies generate large amounts of data, which may reveal new species of
      thermophilic fungi in different substrates (composting systems, geothermal areas,
      piles of plant material). As discussed in this study, there are intrinsic
      problems associated with this method, considering the actual state of the
      taxonomy of thermophilic fungi. To overcome such difficulties, the taxonomic
      classification of this group should move towards standardizing the commonly used
      species names in industry and to assess the possibility of including new systems
      for describing species based on environmental sequences. 

PMID- 25399309
TI  - Improved cultivation and metagenomics as new tools for bioprospecting in cold
      environments.
AB  - Only a small minority of microorganisms from an environmental sample can be
      cultured in the laboratory leaving the enormous bioprospecting potential of the
      uncultured diversity unexplored. This resource can be accessed by improved
      cultivation methods in which the natural environment is brought into the
      laboratory or through metagenomic approaches where culture-independent DNA
      sequence information can be combined with functional screening. The coupling of
      these two approaches circumvents the need for pure, cultured isolates and can be
      used to generate targeted information on communities enriched for specific
      activities or properties. Bioprospecting in extreme environments is often
      associated with additional challenges such as low biomass, slow cell growth,
      complex sample matrices, restricted access, and problematic in situ analyses. In
      addition, the choice of vector system and expression host may be limited as few
      hosts are available for expression of genes with extremophilic properties. This
      review summarizes the methods developed for improved cultivation as well as the
      metagenomic approaches for bioprospecting with focus on the challenges faced by
      bioprospecting in cold environments. 

PMID- 25399311
TI  - Description of gamma radiation-resistant Geodermatophilus dictyosporus sp. nov.
      to accommodate the not validly named Geodermatophilus obscurus subsp.
      dictyosporus (Luedemann, 1968).
AB  - A gamma radiation-resistant, Gram reaction-positive, aerobic and
      chemoorganotrophic actinobacterium, initially designated Geodermatophilus
      obscurus subsp. dictyosporus G-5(T), was not validly named at the time of initial
      publication (1968). G-5(T) formed black-colored colonies on GYM agar. The optimal
      growth range was 25-35  degrees C, at pH 6.5-9.5 and in the absence of NaCl.
      Chemotaxonomic and molecular characteristics of the isolate matched those
      described for members of the genus Geodermatophilus. The DNA G + C content of the
      strain was 75.3 mol%. The peptidoglycan contained meso-diaminopimelic acid as
      diagnostic diamino acid. The main polar lipids were phosphatidylcholine,
      diphosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine and one
      unspecified glycolipid; MK-9(H4) was the dominant menaquinone and galactose was
      detected as a diagnostic sugar. The major cellular fatty acids were branched
      chain saturated acids, iso-C16:0 and iso-C15:0. The 16S rRNA gene showed 94.8
      98.4 % sequence identity with the members of the genus Geodermatophilus. Based on
      phenotypic results and 16S rRNA gene sequence analysis, strain G-5(T) is proposed
      to represent a novel species, Geodermatophilus dictyosporus and the type strain
      is G-5(T) (=DSM 43161(T) = CCUG 62970(T) = MTCC 11558(T) = ATCC 25080(T) = CBS
      234.69(T) = IFO 13317(T) = KCC A-0154(T) = NBRC 13317(T)). The INSDC accession
      number is HF970584.

PMID- 25399313
TI  - Erratum to: Force-velocity relationship of leg extensors obtained from loaded and
      unloaded vertical jumps.

PMID- 25399312
TI  - Effects of short duration static stretching on jump performance, maximum
      voluntary contraction, and various mechanical and morphological parameters of the
      muscle-tendon unit of the lower extremities.
AB  - PURPOSE: Static stretching is used in sport practice but it has been associated
      with decrements in force and performance. Therefore, we examined the effect of
      short duration static stretch on the mechano-morphological properties of the m.
      vastus lateralis (VL) muscle tendon unit (MTU) and on the jumping performance.
      METHODS: Eight males and three females (mean +/- SD, 25.5 +/- 3.1 years)
      stretched their lower legs for a 15 or 60 s duration or acted as their own
      control without stretching in a randomized order. In a pre-post design, a passive
      movement (5 degrees /s) and a maximum voluntary knee extension contraction (MVC)
      were performed on dynamometer while the VL tendon and aponeurosis was observed
      via ultrasound. Furthermore, the participants performed countermovement (CMJ) and
      squat jumps (SJ). RESULTS: Repeated measures ANOVA did not show significant
      differences in MVC, active and passive strain, stiffness, elongation, knee joint
      angle range, and jump performance between and within groups. CONCLUSIONS: The
      applied stretch stimuli (15 or 60 s) were not sufficient to trigger adaptations
      in the mechano-morphological properties of the lower extremities MTU which
      therefore did neither affect jump performance nor MVC. As a possible mechanism,
      we hypothesized that the dose-time dependency effect of static stretch might have
      important implications when measuring functional parameters of the MTU and
      performance. Further examination is necessary to elucidate its impact in the
      examination of the MTU mechano-morphological properties.

PMID- 25399314
TI  - Effects of vasodilatation and pressor response on neurovascular coupling during
      dynamic exercise.
AB  - PURPOSE: Visual stimulation increases the blood flow in the posterior cerebral
      artery (PCA), which supplies blood to the visual cortex by neurovascular coupling
      (NVC). Relative contributions of vasodilatation and pressor response on NVC
      during dynamic exercise are still unknown. METHODS: We measured the blood flow
      velocity in the PCA (PCAv) by transcranial Doppler ultrasound flowmetry during
      rest and exercise in 14 healthy males while they performed 12-min submaximal leg
      cycle exercises at mild-, moderate-, and high-intensity, which corresponded to
      heart rates of 120, 140, and 160 bpm, respectively. NVC was estimated as the
      relative change in PCAv from 20 s eye-closing to the peak response during 40 s
      looking at a reversed checkerboard. Conductance index was calculated for
      evaluating vasodilatation as pressure divided by blood flow. RESULTS: In response
      to visual stimulation, a magnitude of vasodilatation was significantly decreased
      under the moderate-intensity, while pressor response was significantly suppressed
      under the high-intensity exercises, compared with the control condition.
      Conversely, peak response to visual stimulation in PCAv was not affected by
      exercise intensity though relative and absolute responses were significantly
      lower in the moderate- and high-intensity exercises than the control. CONCLUSION:
      It is suggested that the contributions of pressor response and vasodilatation
      were modified by exercise intensity, partly playing a role for stabilizing the
      peak response of PCAv with visual stimulation during dynamic exercise.

PMID- 25399315
TI  - Is there an association between liver type fatty acid binding protein and
      severity of preeclampsia?
AB  - OBJECTIVE: The aim of this study was to estimate the level of liver fatty acid
      binding protein (LFABP) in women with preeclampsia. METHOD: A case-control study
      was conducted in 90 pregnant women who were divided into the following three
      groups: normal pregnancy (n = 30), mild-moderate preeclampsia (n = 30), and
      severe preeclampsia (n = 30). Maternal blood samples were obtained during an
      antenatal clinic visit in normal pregnant women, and at the time of diagnosis in
      women with preeclampsia. Serum LFABP levels were measured by the quantitative
      sandwich enzyme immunoassay technique. RESULTS: Serum LFABP level was
      significantly higher in severe and mild-moderate preeclampsia groups than normal
      pregnancy group (1,709.90 +/- 94.82, 1,614.93 +/- 118.22, and 1,532.36 +/- 140.98
      pg/ml, respectively; p < 0.001). In multivariate analysis, the severity of
      preeclampsia was correlated with LFABP level [unadjusted odds ratio (95%
      confidence interval), 1.008 (1.003-1.012), p < 0.001 and LDH 1.063 (1.029-1.099),
      p < 0.001]. CONCLUSION: Maternal serum LFABP level appears to be correlated with
      the severity of the preeclampsia and can be used to confirm the diagnosis.

PMID- 25399316
TI  - The effect of mefenamic acid and ginger on pain relief in primary dysmenorrhea: a
      randomized clinical trial.
AB  - PURPOSE: The aim of the study was to compare the effect of mefenamic acid and
      ginger on pain management in primary dysmenorrhea. METHODS: One hundred and
      twenty-two female students with moderate to severe primary dysmenorrhea were
      randomly allocated to the ginger and mefenamic groups in a randomized clinical
      trial. The mefenamic group received 250 mg capsules every 8 h, and the ginger
      group received 250 mg capsules (zintoma) every 6 h from the onset of menstruation
      until pain relief lasted 2 cycles. The intensity of pain was assessed by the
      visual analog scale. Data were analyzed by descriptive statistics, t test, Chi
      square, Fisher exact test and repeated measurement. RESULTS: The pain intensity
      in the mefenamic and ginger group was 39.01 +/- 17.77 and 43.49 +/- 19.99,
      respectively, in the first month, and 33.75 +/- 17.71 and 38.19 +/- 20.47,
      respectively, in the second month (p > 0.05). The severity of dysmenorrhea, pain
      duration, cycle duration and bleeding volume was not significantly different
      between groups during the study. The menstrual days were more in the ginger group
      in the first (p = 0.01) and second cycle (p = 0.04). Repeated measurement showed
      a significant difference in pain intensity within the groups by time, but not
      between groups. CONCLUSION: Ginger is as effective as mefenamic acid on pain
      relief in primary dysmenorrhea. Ginger does not have adverse effects and is an
      alternative treatment for primary dysmenorrhea.

PMID- 25399317
TI  - Population structure and breeding value of a new type of Brassica juncea created
      by combining A and B genomes from related allotetraploids.
AB  - KEY MESSAGE: Derived amphiploidy helped to resynthesize agronomically superior B.
      juncea germplasm which showed high heterosis in crosses with natural B. juncea .
      This new procedure facilitates a seamless flow of variation across Brassica
      digenomics. Brassica digenomics, artificially resynthesized by hybridizing extant
      genome donor diploids, show poor breeding value due to the linkage drag
      associated with diploid donors. We recently developed a method that involves
      resynthesis through hybridization between related allotetraploids. Derived B.
      juncea was created by combining A and B genomes extant in B. napus and B.
      carinata, respectively. Large genomic and agronomic modifications resulted.
      Population structure analysis based on the DNA polymorphism generated using 108
      locus-specific SSR primers helped to identify three pools of allelic diversity.
      Thirteen progenies with determinate plant growth habit were discovered, and these
      aligned closely with B genome of the donor species like B. nigra and B. carinata.
      The indeterminate group showed greater genetic affinity with extant B. juncea.
      Derived genotypes possessed high agronomic potential. Importantly, high heterosis
      was observed in crosses between derived and natural B. juncea. Some derived
      juncea progenies figured in heterotic combinations during both the years of F 1
      hybrid evaluation. In essence, the hybrids between derived B. juncea and natural
      B. juncea can be considered as interspecific hybrids between B. juncea and B.
      napus for A genome and between B. juncea and B. carinata for B genome. This
      possibly explains their high heterosis-inducing potential. Integrating genetic
      diversity with the inherent breeding value allowed more efficient prediction of
      heterosis. Besides generation of new novel variability of huge economic
      importance and operational simplicity, the method of derived amphiploidy allows a
      seamless flow of heritable variation across Brassica digenomics.

PMID- 25399318
TI  - Variation in genome composition of blue-aleurone wheat.
AB  - KEY MESSAGE: Different blue-aleurone wheats display major differences in
      chromosome composition, ranging from disomic chromosome additions, substitutions,
      single chromosome arm introgressions and chromosome translocation of Thinopyrum
      ponticum. Anthocyanins are of great importance for human health due to their
      antioxidant, anti-inflammatory, anti-microbial and anti-cancerogenic potential.
      In common wheat (Triticum aestivum L.) their content is low. However, elite lines
      with blue aleurone exhibit significantly increased levels of anthocyanins. These
      lines carry introgressed chromatin from wild relatives of wheat such as
      Thinopyrum ponticum and Triticum monococcum. The aim of our study was to
      characterize genomic constitutions of wheat lines with blue aleurone using
      genomic and fluorescence in situ hybridization. We used total genomic DNA of Th.
      ponticum and two repetitive DNA sequences (GAA repeat and the Afa family) as
      probes to identify individual chromosomes. This enabled precise localization of
      introgressed Th. ponticum chromatin. Our results revealed large variation in
      chromosome constitutions of the blue-aleurone wheats. Of 26 analyzed lines, 17
      carried an introgression from Th. ponticum; the remaining nine lines presumably
      carry T. monococcum chromatin undetectable by the methods employed. Of the Th.
      ponticum introgressions, six different types were present, ranging from a
      ditelosomic addition (cv. Blue Norco) to a disomic substitution (cv. Blue Baart),
      substitution of complete (homologous) chromosome arms (line UC66049) and various
      translocations of distal parts of a chromosome arm(s). Different types of
      introgressions present support a hypothesis that the introgressions activate the
      blue aleurone trait present, but inactivated, in common wheat germplasm.

PMID- 25399319
TI  - The prevalence of strabismus in unilateral coronal synostosis.
AB  - BACKGROUND: While there is a clear correlation between unilateral coronal
      synostosis (UCS) and ocular motility abnormalities, the literature provides
      little information as to the true epidemiology of strabismus, or the underlying
      etiology of these paralleled pathologies. The purpose of this study is to
      investigate the rate of oculomotor abnormalities associated with UCS and its
      management. METHODS: A retrospective review of all patients identified to have
      single-suture, nonsyndromic UCS treated by fronto-orbital advancement at a
      tertiary craniofacial referral center from 1977 to 2013 was performed. Inclusion
      criteria mandated complete medical, surgical, and ophthalmological records.
      Patients were evaluated for strabismus both preoperatively and postoperatively,
      and as to whether eye muscle surgery was performed. RESULTS: A total of 181
      patients underwent treatment for UCS at our institution during the study period,
      of which 79 met the inclusion criteria. Twenty-nine patients had strabismus prior
      to any craniofacial surgical intervention. Following fronto-orbital advancement,
      23 patients (46 %) developed a new onset strabismus. Fifty-five patients had no
      change in their preoperative ocular examination, and one patient had resolution
      of preoperative strabismus. Of the 51 patients who had postoperative strabismus,
      30 went on to have eye muscle surgery. There were no statistically significant
      differences in gender (p=0.477), race (p=0.395), sidedness of suture involvement
      (p=0.552), or age at intervention (p=0.66) in comparing the group with new
      postoperative strabismus and those without. CONCLUSIONS: This study sheds new
      light on the prevalence of strabismus in UCS, and more importantly, the risk of
      developing strabismus in the setting of conventional fronto-orbital advancement.
      This data will allow more accurate preoperative counseling and reinforces the
      important role of ophthalmologists as members of the multidisciplinary
      craniofacial team.

PMID- 25399321
TI  - Compensatory mutations occur within the electrostatic interaction range of
      deleterious mutations in protein structure.
AB  - A compensatory mutation (CM) counter balances lethal effects of a deleterious
      mutation (DM), ensuring the persistence of both through natural selection.
      However, little is known about the biological aspects of CMs those restore the
      structural alterations of proteins caused by slightly DMs. Here, by analyzing the
      evolution of the UDP-glycosyltransferase 73B4 protein among monocot-dicot plants,
      we investigate the occurrence of CMs around slightly DMs in 3D space. Our results
      illustrate that CMs exhibit significantly higher tendency to occur within the
      range of electrostatic interaction around the slightly DMs, compared to occurring
      randomly in the protein.

PMID- 25399320
TI  - Solid-state NMR, electrophysiology and molecular dynamics characterization of
      human VDAC2.
AB  - The voltage-dependent anion channel (VDAC) is the most abundant protein of the
      outer mitochondrial membrane and constitutes the major pathway for the transport
      of ADP, ATP, and other metabolites. In this multidisciplinary study we combined
      solid-state NMR, electrophysiology, and molecular dynamics simulations, to study
      the structure of the human VDAC isoform 2 in a lipid bilayer environment. We find
      that the structure of hVDAC2 is similar to the structure of hVDAC1, in line with
      recent investigations on zfVDAC2. However, hVDAC2 appears to exhibit an increased
      conformational heterogeneity compared to hVDAC1 which is reflected in broader
      solid-state NMR spectra and less defined electrophysiological profiles. 

PMID- 25399322
TI  - Inhibitory Effects of JEUD-38, a New Sesquiterpene Lactone from Inula japonica
      Thunb, on LPS-Induced iNOS Expression in RAW264.7 Cells.
AB  - We isolated JEUD-38, a new sesquiterpene lactone from Inula japonica Thunb. JEUD
      38 dramatically attenuated lipopolysaccharide (LPS)-induced nitric oxide (NO)
      production. Consistent with this finding, the protein expression of inducible
      nitric oxide synthase (iNOS) was blocked by JEUD-38 in a concentration-dependent
      manner. To elucidate the mechanism, we examined the effect of JEUD-38 on LPS
      stimulated nuclear factor-kappaB (NF-kappaB) nuclear translocation, inhibitory
      factor-kappaB (IkappaB) phosphorylation, and degradation. JEUD-38 reduced the
      translocation of p65, via abrogating IkappaB-alpha phosphorylation and
      degradation. In addition, JEUD-38 inhibited LPS-stimulated phosphorylation of
      mitogen-activated protein kinases (MAPKs) including extracellular signal
      regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Since iNOS
      as well as the upstream NF-kappaB and MAPKs are known to be closely involved in
      inflammation, these results suggest that JEUD-38 is a promising candidate for
      prevention and therapy of inflammatory diseases. 

PMID- 25399324
TI  - Effects of walking-induced fatigue on gait function and tripping risks in older
      adults.
AB  - BACKGROUND: Fatigue and ageing contribute to impaired control of walking and are
      linked to falls. In this project, fatigue was induced by maximum speed walking to
      examine fatigue effects on lower limb trajectory control and associated tripping
      risk and overall gait functions of older adults. METHODS: Eleven young (18-35
      years) and eleven older adults (>65 years) conducted 5-minute preferred speed
      treadmill walking prior to and following 6-minute maximum fast walking. Spatio
      temporal gait parameters and minimum foot clearance (MFC) were obtained. Maximal
      muscle strength (hamstrings and quadriceps) was measured on an isokinetic
      dynamometer. Heart rate (HR) and rating of perceived exertion (RPE) assessed
      physiological effort and subjective fatigue. Physiological Cost Index computed
      walking efficiency. RESULTS: Fatigue due to fast walking increased step length,
      double support time and variability of step width. Only older adults reduced MFC
      due to fatigue. A trend of longer double support with greater MFC was found in
      the non-dominant limb. Lower walking efficiency was characterised as the ageing
      effect. Older adults did not increase HR during fast walking but higher RPE
      scores were observed. CONCLUSIONS: Older adults can increase tripping risk by 6
      minutes of fast walking possibly by both impaired walking efficiency based on
      cardiac capacity and higher perceived fatigue due to elevated caution level.
      Regardless of age, increased step width variability due to fatigue was observed,
      a sign of impaired balance. Longer double support and greater MFC observed in the
      older adults' non-dominant limb could be an asymmetrical gait adaptation for
      safety.

PMID- 25399323
TI  - Inhibitory Effect of FXa on Secretory Group IIA Phospholipase A2.
AB  - It is well known that the expression level of secretory group IIA phospholipase
      A2 (sPLA2-IIA) is elevated in inflammatory diseases and lipopolysaccharide (LPS)
      upregulates the expression of sPLA2-IIA in human umbilical vein endothelial cells
      (HUVECs). Activated factor X (FXa) is an important enzyme in the coagulation
      cascade responsible for thrombin generation, and it influences cell signaling in
      various cell types by activating protease-activated receptors (PARs). Here, FX or
      FXa was examined for its effects on the expression and activity of sPLA2-IIA in
      HUVECs and mouse. Prior treatment of cells or mouse with FXa inhibited LPS
      induced expression and activity of sPLA2-IIA via interacting with FXa receptor
      (effective cell protease receptor-1, EPR-1). And FXa suppressed the activation of
      cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase
      (ERK) 1/2 by LPS. Therefore, these results suggest that FXa may inhibit LPS
      mediated expression of sPLA2-IIA by suppression of cPLA2 and ERK 1/2. 

PMID- 25399325
TI  - Na/K-ATPase assay in the intact mice lung subjected to perfusion.
AB  - BACKGROUND: Among the characteristics of acute respiratory distress syndrome
      (ARDS) is edema formation and its resolution depends on pneumocyte Na/K-ATPase
      activity. Increased concentration of oleic acid (OA) in plasma induces lung
      injury by targeting Na/K-ATPase and, thus, interfering in sodium transport.
      FINDINGS: Presently, we adapted a radioactivity-free assay to detect Na/K-ATPase
      activity in perfused lung mice, comparing the inhibitory effect of ouabain and
      OA. We managed to perfuse only the lung, avoiding the systemic loss of rubidium.
      Rb+ incorporation into lung was measured by inductively coupled plasma optical
      emission spectrometry (ICP OES) technique, after lung tissue digestion. Na/K
      ATPase activity was the difference between Rb+ incorporation with or without
      ouabain. Lung Na/K-ATPase was completely inhibited by perfusion with ouabain.
      However, OA caused a partial inhibition. CONCLUSIONS: In the present work the
      amount of incorporated Rb+ was greater than seen in our previous report, showing
      that the present technique is trustworthy. This new proposed assay may allow
      researchers to study the importance of Na/K-ATPase activity in lung
      pathophysiology.

PMID- 25399326
TI  - TL1-A can engage death receptor-3 and activate NF-kappa B in endothelial cells.
AB  - BACKGROUND: Death receptors (DRs) play an important role in renal pathology. We
      have shown that DR3 is inducibly expressed on renal tubular epithelial cells in
      the setting of inflammatory injuries. In this study we investigate the expression
      of DR3 in renal endothelial cells and their response to TL1A, the only known
      ligand of DR3. METHODS: We did RT-PCR, flow cytometry and subcellular
      immunoblotting to examine the expression and function of DR3 in cells in vitro.
      We did organ culture of human and mouse tissue to examine expression and signal
      of DR3 in vivo. RESULTS: DR3 is expressed in some interstitial vascular
      endothelial cells (EC) in human kidney in situ; these EC also respond to its
      ligand TL1A by activating NF-kappaB. Very low levels of DR3 can be detected on
      the cell surface of cultured human umbilical vein (HUV) EC, which do not respond
      to TL1A. HUVEC transfected to overexpress DR3 become responsive to TL1A, assessed
      by IkappaBalpha degradation and E-selectin induction, indicating that the
      signaling components needed for DR3 responsiveness are expressed. TL1A induces NF
      kappaB activation in EC in renal and cardiac tissue from wild type but not DR3
      knock-out mice. CONCLUSION: TL1A and DR3 activate NF-kappaB in vascular
      endothelial cells, and can be an important regulator of renal interstitial
      vascular injury.

PMID- 25399328
TI  - The consequences of cirrhosis in America.

PMID- 25399327
TI  - Management and disease outcome of type I gastric neuroendocrine tumors: the Mount
      Sinai experience.
AB  - BACKGROUND AND AIM: The incidence of gastric neuroendocrine tumors (NETs) has
      increased tenfold since the 1970s. Our aim was to describe the clinicopathologic
      profile, management, and outcomes of type I gastric NETs at The Mount Sinai
      Hospital. METHODS: From existing databases of the Mount Sinai Division of
      Gastrointestinal Pathology and the Carcinoid Cancer Foundation, we identified 56
      patients with type I gastric NETs seen at The Mount Sinai Hospital from 1993 to
      2012. We generated a comprehensive dataset encompassing demographic, clinical,
      endoscopic, and pathologic factors. Survival information was determined from
      medical records and the Social Security Death Index. Tumor-node-metastasis
      staging was conducted, and tumors were graded based on mitotic counts and Ki67
      index. RESULTS: Median NET size was 3.0 mm; 55.8 % displayed multifocal disease.
      Stages I, II, III, and IV disease were observed in 83.8, 10.8, 5.4, and 0 %,
      respectively. Tumors were either low (69.7 %) or intermediate (30.3 %) grade.
      Furthermore, 3.6 % of patients developed gastric dysplasia, and 5.5 % had gastric
      adenocarcinoma. Patients underwent endoscopy every 15 months, while 28.6 %
      underwent polypectomy, 32.7 % somatostatin therapy, and 46.4 % surgical
      resection. 5- and 10-year disease-specific survival was 100 %. CONCLUSIONS: Most
      patients received annual endoscopic surveillance, with a minority undergoing
      surgical resection, though outcomes remained excellent independent of therapeutic
      approach. We identified a very low but real rate of loco-regional spread, despite
      the generally indolent behavior of type I gastric NETs. Several patients
      demonstrated concurrent dysplasia or adenocarcinoma, underscoring the efficacy of
      regular endoscopic management not only for gastric NETs, but also for dysplasia
      and adenocarcinoma.

PMID- 25399329
TI  - Trend of improving prognosis of hepatocellular carcinoma in clinical practice: an
      Italian in-field experience.
AB  - BACKGROUND: Recent data suggest that outcome of hepatocarcinoma is improving.
      AIMS: In order to explore whether survival is also increasing in clinical
      practice, we compared two multicenter independent in-field cohorts of cirrhotics
      with newly diagnosed HCCs. METHODS: Cohort 1 (C1) consisted of 327 patients
      enrolled between January and December 1998, and cohort 2 (C2) included 826
      patients enrolled between September 2008 and November 2012. Patients were
      stratified according to Child-Pugh score, MELD score, and HCC staged according to
      TNM, BCLC systems. RESULTS: At baseline, C2 patients were significantly older,
      with more frequent comorbidities and better liver function. In C2, HCC was more
      frequently detected under regular ultrasound surveillance (P < 0.001), BCLC early
      stages were more frequent, and rates of smaller and uni/paucinodular tumors were
      significantly higher. Treatment of any type was more frequently offered to C2
      patients (P < 0.001). Proportion of patients treated by TACE increased, and
      radiofrequency ablation was the most used ablative treatment. Survival rate was
      significantly higher in C2 being C1 and C2 survival at 1-3 years 72-25 and 75-44
      %, respectively. Child-Pugh score A, BCLC stage A, single nodule, size <= 3 cm,
      belonging to cohort C2 and treatment per se independently predicted survival.
      CONCLUSIONS: This in-field study showed a trend on improved HCC outcomes over
      time, which seems to be mainly due to a better presentation thanks to the wider
      application of surveillance and increased propensity to treat patients. These
      encouraging data should support further efforts to implement such approach to HCC
      in everyday clinical practice.

PMID- 25399331
TI  - Fat and fiber: how the controlled attenuation parameter complements noninvasive
      assessment of liver fibrosis.

PMID- 25399330
TI  - Role of Nrf2 dysfunction in uremia-associated intestinal inflammation and
      epithelial barrier disruption.
AB  - BACKGROUND: Gut inflammation is prevalent in chronic kidney disease (CKD) and
      likely contributes to systemic inflammation via disruption of the epithelial
      tight junction with subsequent endotoxin and bacterial translocation. AIMS: To
      study the expression profile of inflammatory and tight junction proteins in the
      colon from CKD rats compared to healthy controls, and demonstrate the role of
      Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a
      potent Nrf2 activator. METHODS: CKD was induced via 5/6 nephrectomy in Sprague
      Dawley rats, and dh404 (2 mg/kg/day) was used to study the effects of systemic
      Nrf2 activation. The experimental groups included sham, CKD and CKD+ dh404 rats.
      Blood and colon tissues were analyzed after a 10-week study period. RESULTS:
      Colon from CKD rats showed histological evidence of colitis, depletion of
      epithelial tight junction proteins, significant reduction of Nrf2 and its
      measured target gene products (NQO1, catalase, and CuZn SOD), activation of NFkB,
      and upregulation of pro-inflammatory molecules (COX-2, MCP-1, iNOS, and
      gp91(phox)). Treatment with dh404 attenuated colonic inflammation, restored Nrf2
      activity and levels of NQO1, catalase and CuZn SOD, decreased NFkB and lowered
      expression of COX-2, MCP-1, iNOS, and gp91(phox). This was associated with
      restoration of colonic epithelial tight junction proteins (occludin and claudin
      1). CONCLUSIONS: CKD rats exhibited colitis, disruption of colonic epithelial
      tight junction, activation of inflammatory mediators, and impairment of Nrf2
      pathway. Treatment with an Nrf2 activator restored Nrf2 activity, attenuated
      colonic inflammation, and restored epithelial tight junction proteins.

PMID- 25399332
TI  - Clinical utility of wireless motility capsule in patients with suspected
      multiregional gastrointestinal dysmotility.
AB  - BACKGROUND: Patients with gastrointestinal (GI) dysmotility often experience
      overlapping upper and lower GI symptoms suggestive of multiregional involvement.
      Wireless motility capsule (WMC) provides a full GI tract transit profile and may
      be able to detect and diagnose multiregional dysmotility. AIM: To determine the
      clinical utility and diagnostic yield of WMC in patients with upper and lower GI
      symptoms suggestive of multiregional GI dysmotility. METHODS: Retrospective chart
      review of all patients who had undergone WMC testing for suspected multiregional
      GI dysmotility from January 2009 to December 2012 at our institution was
      performed. Information regarding demographics, symptoms, medication use, prior
      diagnostic studies, and results of WMC testing was collected. RESULTS: A total of
      161 patients were included in the analysis. Mean age was 43 +/- 15 years, and 83
      % were female. WMC was abnormal in 109 (67.7 %) subjects. Of these, 17 (15.6 %)
      patients had isolated delayed gastric emptying, 13 (11.9 %) patients had isolated
      delayed small bowel transit, and 25 (22.9 %) patients had isolated delayed large
      bowel transit. Multiregional dysmotility was diagnosed in 54 (49.5 %) patients.
      There was no significant difference in past medical or past surgical history
      between patients with isolated regional versus multiregional involvement. The
      presence or absence of various patient-reported symptoms by history did not
      predict an abnormal WMC study. CONCLUSIONS: Patients' symptoms are poor
      predictors of GI dysmotility and its anatomical extent. WMC can be a useful
      diagnostic test in these patients as it provides a comprehensive evaluation of
      the motility profile of the entire GI tract and provides objective evidence of
      multiregional involvement.

PMID- 25399333
TI  - Malignant acanthosis nigricans associated with prostate cancer: a case report.
AB  - BACKGROUND: Acanthosis nigricans is characterized by hyperpigmentation and
      hyperkeratosis of the skin or mucous membranes. Its malignant form is associated
      with internal neoplasms, especially gastric adenocarcinoma (55-61%). Coexistence
      with prostate cancer is uncommon. In the paraneoplastic type of this dermatosis,
      the skin and mucous lesions are characteristically of more sudden onset and more
      severe than those in the benign form. The efficacy of various treatment
      strategies remains disappointing. CASE PRESENTATION: We here report a case of 66
      year-old Caucasian patient with metastatic prostate cancer and a mild form of
      acanthosis nigricans that preceded the diagnosis of malignancy and resolved with
      chemotherapy in parallel with the prostate cancer. The dermatosis recurred when
      the prostate cancer progressed. CONCLUSION: Concurrent acanthosis nigricans and
      prostate cancer is rare, and few such cases have been reported. Anti-tumor
      therapy occasionally results in regression of this dermatosis. Underlying
      malignant disease should be suspected in individuals with elderly-onset of
      acanthosis nigricans.

PMID- 25399334
TI  - RNA-Seq reveals a xenobiotic stress response in the soybean aphid, Aphis
      glycines, when fed aphid-resistant soybean.
AB  - BACKGROUND: While much recent research has expanded our understanding of the
      molecular interactions between aphids and their host plants, it is lacking for
      the soybean aphid, Aphis glycines. Since its North American invasion, A. glycines
      has become one of the most damaging insect pests on this important crop. Five
      soybean genes for host plant resistance to A. glycines have been identified, but
      populations of A. glycines have already adapted to overcome these resistance
      genes. Understanding the molecular interactions between resistant soybean and A.
      glycines can provide clues to its adaptation mechanisms. Here, we used RNA
      Sequencing to compare and contrast A. glycines gene expression when fed resistant
      (Rag1) and susceptible soybean. RESULTS: Combining results from a previous A.
      glycines transcriptome, we generated 64,860 high quality transcripts, totaling
      41,151,086 bases. Statistical analysis revealed 914 genes with significant
      differential expression. Most genes with higher expression in A. glycines on
      resistant plants (N = 352) were related to stress and detoxification such as
      cytochrome P450s, glutathione-S-transferases, carboxyesterases, and ABC
      transporters. A total of 562 genes showed lower transcript abundance in A.
      glycines on resistant plants. From our extensive transcriptome data, we also
      identified genes encoding for putative salivary effector proteins (N = 73). Among
      these, 6 effector genes have lower transcript abundance in A. glycines feeding on
      resistant soybean. CONCLUSIONS: Overall, A. glycines exhibited a pattern typical
      of xenobiotic challenge, thereby validating antibiosis in Rag1, presumably
      mediated through toxic secondary metabolites. Additionally, this study identified
      many A. glycines genes and gene families at the forefront of its molecular
      interaction with soybean. Further investigation of these genes in other biotypes
      may reveal adaptation mechanisms to resistant plants.

PMID- 25399335
TI  - Pulmonary hilar lymph node metastasis of breast cancer induced bronchopleural
      fistula and superior vena cava syndrome.
AB  - BACKGROUND: It is extremely rare for pulmonary hilar lymph node metastasis
      (PHLNM) of a cancer to be independently lethal. Here, we report an exceedingly
      rare case of cavitation in PHLNM from breast cancer triggering broncho-pleural
      fistula and empyema (BPFE), complicated with superior vena cava syndrome (SVCS).
      CASE REPORT: A 56-year-old woman who had undergone left segmental mastectomy and
      axillary lymph node dissection due to left breast cancer was then treated for 1
      year with postoperative adjuvant chemotherapy. Recurrence of right PHLNM was
      observed 2 years after the operation, for which 3 courses of bevacizumab (BEV)
      and paclitaxel combination chemotherapy were administered. The woman had dyspnea
      and fever during the washout period, and CT examination revealed fistula
      formation between the right PHLNM cavitation and right main bronchus, so she was
      admitted for further treatment. This fistula rapidly progressed to BPFE, and
      contralateral aspiration was observed to cause pneumonia of the left lung. In
      addition, edema of both upper limbs and head and neck were observed, and CT
      examination revealed SVCS caused by re-enlargement of PHLNM. Active treatment was
      performed, but the recommencement of chemotherapy was not possible, and she died
      on Day 150 of admission. CONCLUSIONS: We think that PHLNM deteriorated to central
      necrosis due to chemotherapy with BEV taking effect, leading to formation of
      BPFE. The case was also made more difficult due to the complication of SVCS
      caused by the re-enlarged PHLNM.

PMID- 25399336
TI  - Glycogen metabolism and the homeostatic regulation of sleep.
AB  - In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on
      a key role of glycogen. It was postulated that a major function of sleep is to
      replenish glycogen stores in the brain that have been depleted during wakefulness
      which is associated to an increased energy demand. Astrocytic glycogen depletion
      participates to an increase of extracellular adenosine release which influences
      sleep homeostasis. Here, we will review some evidence obtained by studies
      addressing the question of a key role played by glycogen metabolism in sleep
      regulation as proposed by this hypothesis or by an alternative hypothesis named
      "glycogenetic" hypothesis as well as the importance of the confounding effect of
      glucocorticoids. Even though actual collected data argue in favor of a role of
      sleep in brain energy balance-homeostasis, they do not support a critical and
      direct involvement of glycogen metabolism on sleep regulation. For instance,
      glycogen levels during the sleep-wake cycle are driven by different physiological
      signals and therefore appear more as a marker-integrator of brain energy status
      than a direct regulator of sleep homeostasis. In support of this we provide
      evidence that blockade of glycogen mobilization does not induce more sleep
      episodes during the active period while locomotor activity is reduced. These
      observations do not invalidate the energy hypothesis of sleep but indicate that
      underlying cellular mechanisms are more complex than postulated by Benington and
      Heller. 

PMID- 25399338
TI  - Differential role of STIM1 and STIM2 during transient inward (T in) current
      generation and the maturation process in the Xenopus oocyte.
AB  - BACKGROUND: The Xenopus oocyte is a useful cell model to study Ca2+ homeostasis
      and cell cycle regulation, two highly interrelated processes. Here, we used
      antisense oligonucleotides to investigate the role in the oocyte of stromal
      interaction molecule (STIM) proteins that are fundamental elements of the store
      operated calcium-entry (SOCE) phenomenon, as they are both sensors for Ca2+
      concentration in the intracellular reservoirs as well as activators of the
      membrane channels that allow Ca2+ influx. RESULTS: Endogenous STIM1 and STIM2
      expression was demonstrated, and their synthesis was knocked down 48-72 h after
      injecting oocytes with specific antisense sequences. Selective elimination of
      their mRNA and protein expression was confirmed by PCR and Western blot analysis,
      and we then evaluated the effect of their absence on two endogenous responses:
      the opening of SOC channels elicited by G protein-coupled receptor (GPCR)
      activated Ca2+ release, and the process of maturation stimulated by progesterone.
      Activation of SOC channels was monitored electrically by measuring the T in
      response, a Ca2+-influx-dependent Cl- current, while maturation was assessed by
      germinal vesicle breakdown (GVBD) scoring and electrophysiology. CONCLUSIONS: It
      was found that STIM2, but not STIM1, was essential in both responses, and T in
      currents and GVBD were strongly reduced or eliminated in cells devoid of STIM2;
      STIM1 knockdown had no effect on the maturation process, but it reduced the T in
      response by 15 to 70%. Thus, the endogenous SOCE response in Xenopus oocytes
      depended mainly on STIM2, and its expression was necessary for entry into meiosis
      induced by progesterone.

PMID- 25399339
TI  - Factors influencing ultrasonographic remission in patients with rheumatoid
      arthritis.
AB  - The aim of this study was to define the ultrasonographic factors that indicate
      clinical remission in patients with RA. We enrolled a cohort of patients with RA
      in whom the disease had been in remission for at least 6 months. Musculoskeletal
      ultrasound (US) examination was used to evaluate the status of active synovitis,
      power Doppler (PD) signalling, and synovitis in the bilateral
      metacarpophalangeal; proximal interphalangeal; and radiocarpal, ulnocarpal, and
      intercarpal, compartments of the wrist. A total of 64 RA patients with a mean
      disease duration of 79.97 months were studied. Of all patients, 36% had
      ultrasonographic synovitis and 29% an increased PD signal from at least one
      joint. Delay in diagnosis was highly correlated with synovitis and PD synovitis
      (r = 0.55, p = 0.000; and r = 0.51, p = 0.001, respectively). A weak negative
      correlation was evident between synovitis, PD synovitis, tenosynovitis, PD
      tenosynovitis, and duration of clinical remission (respectively, r = -0.426, p =
      0.000; r = -0.333, p = 0.007; r = -0.243, p = 0.050; and r = -0.247, p = 0.049).
      Upon multivariate logistic regression analysis, the duration of clinical
      remission and delay in diagnosis were the factors that most influenced
      ultrasonographic remission (OR 3.46, p = 0.046; OR 3.27, p = 0.016,
      respectively). Synovial inflammation may persist in RA patients exhibiting
      clinical remission. We found that US detected subclinical synovitis. The most
      important factors preventing ultrasonographic remission were a short duration of
      clinical remission and delay in diagnosis.

PMID- 25399337
TI  - Role of insulin resistance in Alzheimer's disease.
AB  - A critical role of insulin resistance (IR) in Alzheimer's disease (AD) includes
      beta-amyloid (Abeta) production and accumulation, the formation of
      neurofibrillary tangles (NFTs), failure of synaptic transmission and neuronal
      degeneration. Abeta is sequentially cleavaged from APP by two proteolytic
      enzymes: beta-secretase and gamma-secretase. IR could regulate Abeta production
      via enhancing beta- and gamma-secretase activity. Meanwhile, IR induces oxidative
      stress and inflammation in the brain which contributes to Abeta and tau
      pathology. Abeta accumulation can enhance IR through Abeta-mediated inflammation
      and oxidative stress. IR is a possible linking between amyloid plaques and NFTs
      pathology via oxidative stress and neuroinflammation. Additionally, IR could
      disrupt acetylcholine activity, and accelerate axon degeneration and failures in
      axonal transport, and lead to cognitive impairment in AD. Preclinical and
      clinical studies have supported that insulin could be useful in the treatment of
      AD. Thus, an effective measure to inhibit IR may be a novel drug target in AD. 

PMID- 25399340
TI  - Floral morphology and embryology of Helwingia (Helwingiaceae, Aquifoliales):
      systematic and evolutionary implications.
AB  - Helwingia, a shrub or small tree of four species distributed in East Asia, has
      been assigned to various families, mainly Cornaceae. However, molecular analyses
      show that the genus belongs to its own family Helwingiaceae which is sister to
      Phyllonomaceae (Phyllonoma only) in the order Aquifoliales. On the basis of H.
      japonica, we investigated the poorly understood floral and embryological
      characters of Helwingia, and compared their features with those of other
      Aquifoliales, particularly those of Phyllonomaceae. Results showed that perianth
      leaves of Helwingia represent sepals, because in plesiomorphic pentamerous
      flowers, they agreed in position with sepals (not with petals) in pentamerous
      flowers of Phyllonoma. Overall comparisons based on available information show
      that, while sharing with Phyllonoma the epiphyllous inflorescence, the inferior
      ovary, and an epigynous disc nectary as syapomorphies, Helwingia is characterized
      by loss of petals, obhaplostemony, large recurved stigmas, poorly developed disc
      nectary, tenuinucellate ovules with a mature female gametophyte filled with
      densely stained cytoplasm, and a thin mature seed coat. Morphological evidence,
      like molecular evidence, confirms that Helwingia is sufficiently distinct to be
      placed in its own family. Morphological and field observations suggest wind and
      insect pollination in H. japonica, which is the first example of ambophily in
      Aquifoliales. 

PMID- 25399341
TI  - Efficacy and histopathological esophageal wall damage of biodegradable esophageal
      stents for treatment of severe refractory esophageal anastomotic stricture in a
      child with long gap esophageal atresia.
AB  - A case in which a self-expandable biodegradable (BD) esophageal stent was used
      for a refractory esophageal anastomotic stricture (EAS) in a 5-year-old female is
      presented. The patient underwent closure of a tracheoesophageal fistula and
      gastrostomy in the neonatal period. Esophagoesophagostomy was performed at 18
      months of age after a multistaged extrathoracic esophageal elongation procedure.
      The patient developed refractory EAS and required repeated esophageal balloon
      dilation. Four sessions of esophageal BD stenting were performed from the age of
      5-8 years. Each BD stenting allowed her to eat chopped food, but the anastomotic
      stricture recurred 4-7 months after the procedure. No major complications were
      observed, though transient chest pain and dysphagia were observed after each
      stenting. Finally, at 8 years of age, EAS resection and esophagoesophageal
      anastomosis were performed. The resected specimens showed thickened scar
      formation at the EAS lesion, while the degree of esophageal wall damage, both at
      the proximal and distal ends of the stricture, was slight. To the best of our
      knowledge, this is the first case report of this kind of treatment and assessment
      of damage to the esophageal wall microscopically. The advantages and problems of
      the use of BD stents in children are discussed.

PMID- 25399342
TI  - Erythrocyte glutathione transferase in uremic diabetic patients: additional data.

PMID- 25399343
TI  - Ethnic disparities in insulin and glucose-dependent insulinotropic peptide (GIP)
      responses to intraduodenal glucose in health.

PMID- 25399344
TI  - Past and present of interposition arthroplasties for joint repair with special
      tribute to the contribution by Vittorio Putti.
AB  - Several techniques have been proposed to restore the compromised function of a
      joint. These include the arthroplasty by placing various tissues or materials
      between the articular surfaces. An important contribution to the diffusion of
      arthroplasty techniques was made by Vittorio Putti, head of the Rizzoli
      Orthopedic Institute in Bologna from 1912 to 1940. Interposition arthroplasty is
      still used for some non-weight-bearing joints, such as wrist and elbow, and gives
      good results. This type of surgery has been further developed by the improvement
      in biomaterials, biomechanical studies and the regenerative medicine. This paper
      describes the development starting from a historical survey particularly focused
      on Putti's contribution and ending with the state of the art of regenerative
      medicine in the treatment of joint diseases. Level of evidence V.

PMID- 25399345
TI  - Assessing the accuracy of patient-specific guides for total knee arthroplasty.
AB  - PURPOSE: Patient-specific guides have been introduced recently as a means of
      making accurate bone cuts through custom cutting blocks constructed based on pre
      operative three-dimensional imaging. However, the controversy concerning the
      improved results of patient-specific guides have not been resolved yet; in
      addition, there have been no studies to investigate the causes of variable with
      inconsistent results and solutions for the causes. METHODS: Thirty eight patients
      (38 knees) underwent total knee arthroplasty with patient-specific guides. The
      mean age of the patients was 68 years (SD +/- 6.3), and all patients had a
      minimum 2-year follow-up. An intra-operative alignment using navigation and the
      causes of outliers were evaluated. RESULTS: An average coronal alignment of PSI
      jigs was 0.5 degrees  (SD +/- 0.9 degrees ) in femur and 0.1 degrees  (SD +/- 0.8
      degrees ) in tibia, and the number of outliers was two and three cases,
      respectively. An average sagittal alignment was 0.6 degrees  (SD +/- 0.9 degrees
      ) in femur and 5.5 degrees  (SD +/- 1.1 degrees ) in tibia, and the number of
      outliers was three and five cases, respectively. All outliers resulted from large
      osteophytes near the contact point of patient-specific guides which disturb
      sitting of the guide. CONCLUSION: It was suggested that patient-specific guides
      were an effective and safe method to achieve accurate alignments, with no
      additional intra-operative complication. It is important to note that surgeons
      need to be precautious using the patient-specific instrumentation in patients
      with severe varus deformity. In addition, existing osteophytes which disturb
      sitting of the guides should be carefully evaluated pre-operatively and intra
      operatively. LEVEL OF EVIDENCE: IV.

PMID- 25399346
TI  - Significant influence of rotational limb alignment parameters on patellar
      kinematics: an in vitro study.
AB  - PURPOSE: Component malrotation has a major impact on patellar kinematics in total
      knee arthroplasty. The influence of natural rotational limb alignment on patellar
      kinematics is unclear so far. Based on recent clinical investigations, we
      hypothesized that rotational limb alignment significantly influences patellar
      kinematics. METHODS: Patellar kinematics of ten cadaveric knees was measured
      using computer navigation during passive motion. Data were correlated with
      different rotational limb alignment parameters of preoperative CT scans. RESULTS:
      Femoral antetorsion showed a significant influence on patellar rotation, while
      tibial tubercle-posterior cruciate ligament distance additionally displayed a
      significant influence on patellar mediolateral shift (p < 0.05). Femoral
      posterior condylar angle was sensitive to patellar epicondylar distance, rotation
      and tilt (p < 0.05). Patellar rotation was influenced by five out of eight
      rotational limb alignment parameters (p < 0.05). CONCLUSIONS: Rotational limb
      alignment should be paid more attention in terms of clinical evaluation of
      patellar tracking and future biomechanical and clinical investigations.

PMID- 25399347
TI  - Inter- and intraobserver reliability of the Rockwood classification in acute
      acromioclavicular joint dislocations.
AB  - PURPOSE: The reliability of the Rockwood classification, the gold standard for
      acute acromioclavicular (AC) joint separations, has not yet been tested. The
      purpose of this study was to investigate the reliability of visual and measured
      AC joint lesion grades according to the Rockwood classification. METHODS: Four
      investigators (two shoulder specialists and two second-year residents) examined
      radiographs (bilateral panoramic stress and axial views) in 58 patients and
      graded the injury according to the Rockwood classification using the following
      sequence: (1) visual classification of the AC joint lesion, (2) digital
      measurement of the coracoclavicular distance (CCD) and the horizontal dislocation
      (HD) with Osirix Dicom Viewer (Pixmeo, Switzerland), (3) classification of the AC
      joint lesion according to the measurements and (4) repetition of (1) and (2)
      after repeated anonymization by an independent physician. Visual and measured
      Rockwood grades as well as the CCD and HD of every patient were documented, and a
      CC index was calculated (CCD injured/CCD healthy). All records were then used to
      evaluate intra- and interobserver reliability. RESULTS: The disagreement between
      visual and measured diagnosis ranged from 6.9 to 27.6 %. Interobserver
      reliability for visual diagnosis was good (0.72-0.74) and excellent (0.85-0.93)
      for measured Rockwood grades. Intraobserver reliability was good to excellent
      (0.67-0.93) for visual diagnosis and excellent for measured diagnosis (0.90
      0.97). The correlations between measurements of the axial view varied from 0.68
      to 0.98 (good to excellent) for interobserver reliability and from 0.90 to 0.97
      (excellent) for intraobserver reliability. CONCLUSION: Bilateral panoramic stress
      and axial radiographs are reliable examinations for grading AC joint injuries
      according to Rockwood's classification. Clinicians of all experience levels can
      precisely classify AC joint lesions according to the Rockwood classification. We
      recommend to grade acute ACG lesions by performing a digital measurement instead
      of a sole visual diagnosis because of the higher intra- and interobserver
      reliability. LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 25399348
TI  - Predictors of Remission of T2DM and Metabolic Effects after Laparoscopic Roux-en
      y Gastric Bypass in Obese Indian Diabetics-a 5-Year Study.
AB  - BACKGROUND: Bariatric surgery has proven results for diabetes remission in obese
      diabetics. Despite this, a lot of ambiguity exists around patient selection. The
      objectives of this study are the following: (1) evaluation of results of
      laparoscopic Roux-en-y gastric bypass (LRYGB) in obese type 2 diabetic (T2DM)
      Indian patients at 5 years and (2) to define predictors of success after surgery.
      METHODS: This is a prospective observational study. One hundred six Indian
      patients underwent LRYGB from January 2004 to July 2009. Patients were evaluated
      for percent excess weight loss (%EWL) and remission of T2DM. Mean age 50.34 +/-
      9.08 years, mean waist circumference 129.8 +/- 20.8 cm, mean weight 119.2 +/-
      23.6 kg, mean BMI 45.01 +/- 7.9 kg/m(2), and mean duration of diabetes 8.2 +/-
      6.2 years. RESULTS: At 5 years, mean EWL% was 61.4 +/- 20.3, mean weight regain
      of 8.6 +/- 6.2 kg was seen in 63.6 %, mean glycosylated hemoglobin dropped from
      8.7 +/- 2.1 to 6.2 +/- 01.3 %, mean triglycerides declined by 31 %, and serum
      high density lipoprotein rose by 18.4 %. Mean low-density lipoprotein levels
      declined by 6.8 %. Age, BMI, fasting C-peptide levels, duration of T2DM, and pre
      op use of insulin emerged as significant predictors of success after surgery. One
      hundred percent remission was seen in patients with T2DM <5 years. CONCLUSIONS:
      LRYGB is safe and efficacious for long-term remission of T2DM (BMI >= 35
      kg/m(2)). In a country with the second largest population of type 2 diabetics in
      the world, predictors of success after surgery can help in prioritizing patients
      who have a greater chance to benefit from metabolic surgery.

PMID- 25399349
TI  - Reliability of Continuous Non-Invasive Assessment of Hemoglobin and Fluid
      Responsiveness: Impact of Obesity and Abdominal Insufflation Pressures.
AB  - BACKGROUND: During surgery, proper fluid resuscitation and hemostatic control is
      critical. Pleth variability index (PVI) is advocated as a reliable way of
      optimizing intraoperative fluid resuscitation. PVI is a measure of dynamic change
      in perfusion index during a complete respiratory cycle. Non-invasive monitoring
      of total hemoglobin could provide a reliable means to determine need for
      transfusion. We analyzed the impact of insufflation and obesity on non-invasive
      measurements of hemoglobin and PVI in laparoscopic procedures to validate
      reliability of fluid responsiveness and hemoglobin levels. METHODS: A non
      invasive hemoglobin and PVI monitoring device was prospectively analyzed in
      patients undergoing abdominal operations. Patients were stratified by open and
      laparoscopic approach and obesity (body mass index (BMI) >=35). PVI and
      hemoglobin values were assessed before, during, and after insufflation and
      compared to control patients undergoing open surgery. RESULTS: Sixty-three
      patients were enrolled (mean age 42 years; 71 % male; mean BMI 36) with 24
      patients laparoscopic non-obese (LNO), 20 laparoscopic obese (LO), and 19
      undergoing open operations. There was no significant blood loss. Hemoglobin did
      not change significantly before or after insufflation. There was false elevation
      of PVI with insufflation and more pronounced in obese patients. CONCLUSIONS:
      Insufflation or obesity was not associated with significant variations in
      hemoglobin. Non-invasive monitoring of hemoglobin is useful in laparoscopic
      procedures in obese and non-obese patients. PVI values should be used cautiously
      during laparoscopic procedures, particularly in obese patients.

PMID- 25399350
TI  - Continuous-light tolerance in tomato is graft-transferable.
AB  - Continuous light induces a potentially lethal injury in domesticated tomato
      (Solanum lycopersicum) plants. Recently, continuous-light tolerance was reported
      in several wild tomato species, yet the molecular mechanisms underpinning
      tolerance/sensitivity are still elusive. Here, we investigated from which part of
      the plant continuous-light tolerance originates and whether this trait acts
      systemically within the plant. By exposing grafted plants bearing both tolerant
      and sensitive shoots, the trait was functionally located in the shoot rather than
      the roots. Additionally, an increase in continuous-light tolerance was observed
      in sensitive plants when a continuous-light-tolerant shoot was grafted on it.
      Cultivation of greenhouse tomatoes under continuous light promises high yield
      increases. Our results show that to pursuit this, the trait should be bred into
      scion rather than rootstock lines. In addition, identifying the nature of the
      signal/molecule(s) and/or the mechanism of graft-induced, continuous-light
      tolerance can potentially result in a better understanding of important
      physiological processes like long-distance signaling.

PMID- 25399351
TI  - Genome-wide identification and analysis of Catharanthus roseus RLK1-like kinases
      in rice.
AB  - MAIN CONCLUSION: A genome-wide survey of Catharanthus roseus receptor-like
      kinase1-like kinases (CrRLK1Ls) in rice revealed that the pattern of expression
      by some CrRLK1Ls is controlled by drought or circadian rhythms. This is probably
      accomplished through the functioning of Gigantea ( OsGI ). Such findings provide
      a novel angle for using CrRLK1Ls to study the drought-stress response and
      circadian regulation. The 17 CrRLK1L members of a novel RLK family have been
      identified in Arabidopsis. Each carries a putative extracellular carbohydrate
      binding malectin-like domain. However, their roles in rice, a widely consumed
      staple food, are not well understood. To investigate the functions of CrRLK1Ls in
      rice, we utilized phylogenomics data obtained through anatomical and diurnal meta
      expression analyses. This information was integrated with a large set of public
      microarray data within the context of the rice CrRLK1L family phylogenic tree.
      Chromosomal locations indicated that 3 of 16 genes were tandem-duplicated,
      suggesting possible functional redundancy within this family. However, integrated
      diurnal expression showed functional divergence between two of three genes, i.e.,
      peak expression was detected during the day for OsCrRLK1L2, but during the night
      for OsCrRLK1L3. We found it interesting that OsCrRLK1L2 expression was repressed
      in osgigantea (osgi) mutants, which suggests that it could function downstream of
      OsGI. Network analysis associated with OsCrRLK1L2 and OsGI suggested a novel
      circadian regulation mechanism mediated by OsGI. In addition, two of five
      OsCrRLK1Ls preferentially expressed in the roots were stimulated by drought,
      suggesting a potential role for this family in water-use efficiency. This
      preliminary identification of CrRLK1Ls and study of their expression in rice will
      facilitate further functional classifications and applications in plant
      production.

PMID- 25399352
TI  - AtrbohD and AtrbohF negatively regulate lateral root development by changing the
      localized accumulation of superoxide in primary roots of Arabidopsis.
AB  - MAIN CONCLUSION: NADPH oxidase AtrbohD an d AtrbohF negatively modulate lateral
      root development by changing the peroxidase activity and increasing the local
      generation of superoxide in primary roots of Arabidopsis in an auxin-independent
      manner. NADPH oxidase subunits AtrbohD and AtrbohF play pivotal roles in
      regulating growth, development and stress responses in Arabidopsis. However,
      whether they modulate lateral root (LR) formation has not yet been addressed, and
      the detailed mechanisms underlying the process remain unanswered. Here, we show
      that two null double mutants atrbohD1/F1 and atrbohD2/F2, in which both AtrbohD
      and AtrbohF genes are disrupted, had remarkably higher LR density than wild-type
      (WT), or the single mutant atrbohD1 and atrbohF1. Compared to WT, the double
      mutants exhibited early emerged LRs and enhanced density of lateral root
      primordia (LRP). Unexpectedly, the production of superoxide (O2 (-)), but not
      hydrogen peroxide, in the mature area of the primary root containing LRs
      significantly increased in the double mutants relative to that in WT. Further
      experiments revealed that the local accumulation of O2 (-) led to the enhancement
      of LR density in the double mutants. Moreover, the deficiency of AtrbohD and
      AtrbohF caused a marked increase in peroxidase activity in the mature root zone,
      which contributed to the localized accumulation of O2 (-) and the elevated LR
      density in the double mutants. Furthermore, the double mutants were not sensitive
      to exogenous auxin naphthalene acetic acid or auxin transport inhibitor 1-N
      naphthylphthalamic acid in terms of LR formation. The auxin response of LRP in
      vivo in atrbohD1/F1 was also similar to that in WT. Taken together, these results
      suggest that AtrbohD and AtrbohF negatively modulate LR development by
      controlling the local generation of superoxide in an auxin-independent manner.
      These findings provide new insights into the mechanisms of NADPH oxidase-mediated
      regulation of LR branching in Arabidopsis.

PMID- 25399353
TI  - Pathohistological changes of tracheal epithelium in laryngectomized patients.
AB  - Total laryngectomy results in a permanent disconnection of the upper and lower
      airways. Thus, the upper airways are bypassed and can no longer condition,
      humidify, and filter the inhaled air, leading to damage of the tracheobronchial
      epithelium. There is little scientific information available about the effects of
      tracheostoma breathing and the degree of mucosal damage in laryngectomized
      patients. The aims of this study were to determine the histopathologic findings
      and investigate the potential impact of using a heat and moisture exchanger (HME)
      on the tracheal epithelium in long-term tracheostomy patients. Tracheal mucosal
      biopsies were taken from a total of 70 patients. Specimens were stained with
      hematoxylin and eosin and examined by a light microscope. Normal pseudostratified
      ciliated columnar epithelium was found in only 9 (12.9%) cases; while, 17 (24.3%)
      cases had some degree of basal cell hyperplasia. Squamous metaplasia was the most
      common finding (50%). Pre-invasive lesions (mild and moderate squamous dysplasia)
      were found in only one patient who used an HME, and in eight (11.4%) non-users.
      Although the HME cannot completely restore the physiological functions of the
      upper respiratory track, it delivers a better quality of air to the lower airways
      and has a positive effect on tracheal mucosa.

PMID- 25399354
TI  - An isolated cryptococcoma mimicking nasopharyngeal cancer.

PMID- 25399355
TI  - Bone marrow-derived TNF-alpha causes diabetic neuropathy in mice.
AB  - AIMS/HYPOTHESIS: Dysregulation of biochemical pathways in response to
      hyperglycaemia in cells intrinsic to the nervous system (Schwann cells, neurons,
      vasa nervorum) are thought to underlie diabetic peripheral neuropathy (DPN). TNF
      alpha is a known aetiological factor; Tnf-knockout mice are protected against
      DPN. We hypothesised that TNF-alpha produced by a small but specific bone marrow
      (BM) subpopulation marked by proinsulin production (proinsulin-producing BM
      derived cells, PI-BMDCs) is essential for DPN development. METHODS: We produced
      mice deficient in TNF-alpha, globally in BM and selectively in PI-BMDCs only, by
      gene targeting and BM transplantation, and induced diabetes by streptozotocin.
      Motor and sensory nerve conduction velocities were used to gauge nerve
      dysfunction. Immunocytochemistry, fluorescence in situ hybridisation (FISH) and
      PCR analysis of dorsal root ganglia (DRG) were employed to monitor outcome.
      RESULTS: We found that loss of TNF-alpha in BM only protected mice from DPN. We
      developed a strategy to delete TNF-alpha specifically in PI-BMDCs, and found that
      PI-BMDC-specific loss of TNF-alpha protected against DPN as robustly as loss of
      total BM TNF-alpha. Selective loss of PI-BMDC-derived TNF-alpha downregulated
      TUNEL-positive DRG neurons. FISH revealed PI-BMDC-neuron fusion cells in the DRG
      in mice with DPN; fusion cells were undetectable in non-diabetic mice or diabetic
      mice that had lost TNF-alpha expression selectively in the PI-BMDC subpopulation.
      CONCLUSIONS/INTERPRETATION: BMDC-specific TNF-alpha is essential for DPN
      development; its selective removal from a small PI-BMDC subpopulation protects
      against DPN. The pathogenicity of PI-BMDC-derived TNF-alpha may have important
      therapeutic implications.

PMID- 25399356
TI  - Efficacy and safety of lanthanum carbonate versus calcium-based phosphate binders
      in patients with chronic kidney disease: a systematic review and meta-analysis.
AB  - PURPOSE: We conducted this review to assess the relative efficacy and safety of
      lanthanum carbonate versus calcium-based phosphate binders in chronic kidney
      disease. METHODS: We systematically searched PubMed, EMBASE, the Cochrane
      Controlled Trial Register of Controlled Trials and Chinese Biological Medical
      Database for randomized controlled trials comparing lanthanum carbonate with
      calcium-based phosphate binders in adult patients with chronic kidney disease.
      Study quality was assessed using the criteria outlined in the Cochrane Handbook
      for Systematic Reviews of intervention. Meta-analysis was conducted by reviewer
      manager software, version 5.3. RESULTS: Eleven trials with 1,501 participants
      were included. Lanthanum carbonate appeared to be associated with a significant
      reduction in progression of vascular calcification and a beneficial effect on
      bone outcomes without aluminum-like toxicity. Lanthanum carbonate achieved
      similar proportions of phosphate-controlled patients (RR 0.63, 95% CI 0.27-1.44)
      with lower incidence of hypercalcemia (RR 0.13, 95% CI 0.05-0.35) in comparison
      with calcium-based phosphate binders. Lanthanum carbonate was associated with
      significantly lower serum calcium, similar serum Ca * P product and higher serum
      iPTH compared with calcium salts in patients with chronic kidney disease.
      CONCLUSION: Lanthanum carbonate could delay the progression of vascular
      calcification and benefit chronic kidney disease patients on bone outcomes.
      Lanthanum carbonate could achieve similar proportion of phosphate-controlled
      patients as calcium-based phosphate binders with lower incidence of
      hypercalcemia.

PMID- 25399357
TI  - Jasmonic acid enhances plant cyanogenesis and resistance to herbivory in lima
      bean.
AB  - Jasmonic acid (JA) is a natural plant hormone ubiquitously distributed in plants
      and centrally involved in the induction of direct and indirect plant defenses.
      Defenses up-regulated by this hormone include trichomes--a direct, mechanical
      defense--and alkaloids--a direct chemical defense--as well as two indirect
      chemical defenses: volatile organic compounds (VOCs) and extrafloral nectar
      (EFN). Plant cyanogenesis--the release of toxic hydrogen cyanide (HCN) from
      preformed cyanogenic precursors in fruits, leaves, and seeds of many plants--is
      recognized as a direct, constitutive plant defensive trait, and is among the most
      widely distributed of all direct chemical plant defenses. The cyanogenic system
      in plants is composed of three parameters: The cyanogenic potential (HCNp;
      concentration of cyanogenic precursors), beta-glucosidase activity, and
      cyanogenic capacity (HCNc; release of gaseous hydrogen cyanide). Here, we
      demonstrated that experimental application of aqueous solutions of JA ranging
      from 0.001 to 1.0 mmol L(-1), as well as insect herbivory significantly enhanced
      HCNc via the induction of beta-glucosidase activity in wild lima bean (Phaseolus
      lunatus L.). In choice feeding trials with JA induced and damaged leaves, adult
      Mexican bean beetles--natural herbivores of lima bean--rejected leaves with
      enhanced beta-glucosidase activity and HCNc. Our findings suggest that jasmonic
      acid plays a critical role in regulating activity of beta-glucosidases, which
      determines the rate of cyanogenesis, and thus mediates direct plant defense
      against herbivores.

PMID- 25399358
TI  - Changes in cause-specific mortality during heat waves in central Spain, 1975
      2008.
AB  - The relationship between heat waves and mortality has been widely described, but
      there are few studies using long daily data on specific-cause mortality. This
      study is undertaken in central Spain and analysing natural causes, circulatory
      and respiratory causes of mortality from 1975 to 2008. Time-series analysis was
      performed using ARIMA models, including data on specific-cause mortality and
      maximum and mean daily temperature and mean daily air pressure. The length of
      heat waves and their chronological number were analysed. Data were stratified in
      three decadal stages: 1975-1985, 1986-1996 and 1997-2008. Heat-related mortality
      was triggered by a threshold temperature of 37  degrees C. For each degree that
      the daily maximum temperature exceeded 37  degrees C, the percentage increase in
      mortality due to circulatory causes was 19.3 % (17.3-21.3) in 1975-1985, 30.3 %
      (28.3-32.3) in 1986-1996 and 7.3 % (6.2-8.4) in 1997-2008. The increase in
      respiratory cause ranged from 12.4 % (7.8-17.0) in the first period, to 16.3 %
      (14.1-18.4) in the second and 13.7 % (11.5-15.9) in the last. Each day of heat
      wave duration explained 5.3 % (2.6-8.0) increase in respiratory mortality in the
      first period and 2.3 % (1.6-3.0) in the last. Decadal scale differences exist for
      specific-causes mortality induced by extreme heat. The impact on heat-related
      mortality by natural and circulatory causes increases between the first and the
      second period and falls significantly in the last. For respiratory causes, the
      increase is no reduced in the last period. These results are of particular
      importance for the estimation of future impacts of climate change on health.

PMID- 25399359
TI  - Post-natal outcomes of antenatally diagnosed intra-abdominal cysts: a 22-year
      single-institution series.
AB  - PURPOSE: The aim of this study was to establish the post-natal diagnosis and
      outcome of antenatally diagnosed intra-abdominal cysts between 1991 and 2013 at
      our institution. METHODS: All antenatally diagnosed intra-abdominal cysts between
      1991 and 2013 were identified using a foetal anomaly database. The cysts were
      monitored for resolution. In all cases where the cyst had not resolved
      antenatally, additional post-natal scans were conducted. Antenatal diagnosis,
      post-natal diagnosis and outcomes were also recorded. RESULTS: 118 cases of
      antenatal intra-abdominal cysts were identified over the 22-year study period
      with a 98 % live birth rate. The overall accuracy of an antenatal diagnosis at
      our institution was 92 %. 26 cases (22 %) resolved spontaneously in utero, the
      majority of which (77 %) were ovarian in nature. Four tumour cases were
      identified in the series, which included two neuroblastomas, one yolk sac tumour
      and one teratoma. 90 cysts persisted post-natally with 52 % requiring surgery.
      These primarily included choledochal and enteric duplication cysts as well as
      symptomatic solid organ cysts. Diagnostic revision was limited to 8 % of cases
      over the study period with an overall improvement over the last decade. Overall,
      40 % of all antenatally diagnosed cysts required surgical intervention. In those
      cysts that persisted post-natally, 52 % required surgery. CONCLUSIONS: A fifth of
      prenatally diagnosed intra-abdominal cysts will resolve with most ovarian cysts
      regressing in utero. Half of all persistent cysts will, however, require surgical
      intervention. These data are useful for prenatal counselling and demonstrates the
      important role played by the paediatric surgeon in the overall management of
      intra-abdominal cysts.

PMID- 25399360
TI  - Genome-wide scan demonstrates significant linkage for male sexual orientation.
AB  - BACKGROUND: Findings from family and twin studies support a genetic contribution
      to the development of sexual orientation in men. However, previous studies have
      yielded conflicting evidence for linkage to chromosome Xq28. METHOD: We conducted
      a genome-wide linkage scan on 409 independent pairs of homosexual brothers (908
      analyzed individuals in 384 families), by far the largest study of its kind to
      date. RESULTS: We identified two regions of linkage: the pericentromeric region
      on chromosome 8 (maximum two-point LOD = 4.08, maximum multipoint LOD = 2.59),
      which overlaps with the second strongest region from a previous separate linkage
      scan of 155 brother pairs; and Xq28 (maximum two-point LOD = 2.99, maximum
      multipoint LOD = 2.76), which was also implicated in prior research. CONCLUSIONS:
      Results, especially in the context of past studies, support the existence of
      genes on pericentromeric chromosome 8 and chromosome Xq28 influencing development
      of male sexual orientation.

PMID- 25399361
TI  - Management of anaphylaxis in an austere or operational environment.
AB  - We present a case report of a Special Operations Soldier who developed
      anaphylaxis as a consequence of a bee sting, resulting in compromise of the
      operation. We review the current literature as it relates to the pathophysiology
      of the disease process, its diagnosis, and its management. An evidence-based
      field treatment algorithm is suggested. 

PMID- 25399362
TI  - Tactical Hemorrhage Control Case Studies Using a Point-of-Care Mechanical Direct
      Pressure Device.
AB  - In 2012, a new hemorrhage control device entered the market, and by May 2013, the
      iTClamp 50 had acquired US Food and Drug Administration approval. The authors
      describe the use of the iTClamp 50 and present two case studies in which the
      iTClamp 50 was successfully used in the military environment to control
      potentially fatal hemorrhage. 

PMID- 25399363
TI  - Prehospital analgesia with ketamine for combat wounds: a case series.
AB  - BACKGROUND: No data have been published on the use of ketamine at the point of
      injury in combat. OBJECTIVE: To provide adequate pain management for severely
      injured Rangers, ketamine was chosen for its analgesic and dissociative
      properties. Ketamine was first used in the 75th Ranger Regiment in 2005 but fell
      out of favor because medical providers had limited experience with its use. In
      2009, with new providers and change in medic training at the battalion level, the
      Regiment implemented a protocol using doses of ketamine that exceed the current
      Tactical Combat Casualty Care recommendations. METHODS: Medical after-action
      reports were reviewed for all Ranger casualties who received ketamine at the
      point of injury for combat wounds from January 2009 to October 2014. Patients and
      medics were also interviewed. RESULTS: Unit medical protocols authorize ketamine
      for tourniquet pain, amputations, long-bone fractures, and pain refractory to
      other agents. Nine of the 11 patients were US Forces; two were local nationals
      (one female, one male). The average initial dose given intramuscularly was 183
      mg, about 2 to 3 mg/kg and intravenously 65 mg, about 1 mg/kg. The patients also
      received an opioid, a benzodiazepine, or both. There was one episode of apnea
      that was corrected quickly with stimulus. Eight of the 11 patients required the
      application of at least one tourniquet; four patients needed between two and four
      tourniquets to control hemorrhage. Pain was assessed with a subjective 1-10
      scale. Before ketamine, the pain was rated as 9-10, with one patient claiming a
      pain level of 8. Of the US Forces, seven of the nine had no pain after receiving
      ketamine and two had a pain level of four. Two of the eight had posttraumatic
      stress disorder. CONCLUSIONS: In this small, retrospective sample of combat
      casualties, ketamine appeared to be a safe and effective battlefield analgesic.

PMID- 25399364
TI  - Tourniquet pressures: strap width and tensioning system widths.
AB  - BACKGROUND: Pressure distribution over tourniquet width is a determinant of
      pressure needed for arterial occlusion. Different width tensioning systems could
      result in arterial occlusion pressure differences among nonelastic strap designs
      of equal width. METHODS: Ratcheting Medical Tourniquets (RMTs; m2 inc.,
      http://www.ratcheting buckles.com) with a 1.9 cm-wide (Tactical RMT) or 2.3 cm
      wide (Mass Casualty RMT) ladder were directly compared (16 recipients, 16 thighs
      and 16 upper arms for each tourniquetx2). Then, RMTs were retrospectively
      compared with the windlass Combat Application Tourniquet (C-A-T ["CAT"],
      http://combattourniquet.com) with a 2.5 cm-wide internal tensioning strap.
      Pressure was measured with an air-filled No. 1 neonatal blood pressure cuff under
      each 3.8 cm-wide tourniquet. RESULTS: RMT circumferential pressure distribution
      was not uniform. Tactical RMT pressures were not higher, and there were no
      differences between the RMTs in the effectiveness, ease of use ("97% easy"), or
      discomfort. However, a difference did occur regarding tooth skipping of the pawl
      during ratchet advancement: it occurred in 1 of 64 Tactical RMT applications
      versus 27 of 64 Mass Casualty RMT applications. CAT and RMT occlusion pressures
      were frequently over 300 mmHg. RMT arm occlusion pressures (175-397 mmHg),
      however, were lower than RMT thigh occlusion pressures (197-562 mmHg). RMT
      effectiveness was better with 99% reached occlusion and 1% lost occlusion over 1
      minute versus the CAT with 95% reached occlusion and 28% lost occlusion over 1
      minute. RMT muscle tension changes (up to 232 mmHg) and pressure losses over 1
      minute (24+/-11 mmHg arm under strap to 40+/-12 mmHg thigh under ladder) suggest
      more occlusion losses may have occurred if tourniquet duration was extended.
      CONCLUSIONS: The narrower tensioning system Tactical RMT has better performance
      characteristics than the Mass Casualty RMT. The 3.8 cm-wide RMTs have some
      pressure and effectiveness similarities and differences compared with the CAT.
      Clinically significant pressure changes occur under nonelastic strap tourniquets
      with muscle tension changes and over time periods as short as 1 minute. An
      examination of pressure and occlusion changes beyond 1 minute would be of
      interest.

PMID- 25399365
TI  - Imaging comparison of pelvic ring disruption and injury reduction with use of the
      junctional emergency treatment tool for preinjury and postinjury pelvic
      dimensions: a cadaveric study with computed tomography.
AB  - OBJECTIVE: Complex dismounted blast injuries from (improvised) explosive devices
      have caused amputations of the lower extremities associated with open injuries to
      the pelvic ring, resulting in life-threatening hemorrhage from disruption of
      blood vessels near the pelvic ring. Provisional stabilization of the skeletal
      pelvis by circumferential pelvic compression provides stability for intrapelvic
      clots and reduces the volume of the pelvis, thereby limiting the amount of
      hemorrhage. The Junctional Emergency Treatment Tool (JETTtm; North American
      Rescue Products, http://www.narescue.com) is a junctional hemorrhage control
      device developed to treat pelvic and lower extremity injuries sustained in high
      energy trauma on the battlefield and in the civilian environment. Our purpose was
      to evaluate the compressive function of the JETT in the reduction of pelvic ring
      injuries in a cadaveric model. METHODS: Radiographic comparison of pre (intact)
      and post pelvic ring disruption and injury was compared with radiographic
      measurements post reduction with the JETT device in two cadavers. The device's
      ability to reduce pelvic disruption and injury in a human cadaver model was
      assessed through measurements of the anteroposterior (AP) and transverse
      diameters obtained at the inlet and outlet of the pelvis. RESULTS: Computed
      tomography (CT) scans demonstrated that JETT application effectively induced
      circumferential soft tissue compression that was evoked near anatomic reduction
      of the sacroiliac joint and symphysis pubis. CONCLUSIONS: The JETT is capable of
      effectively reducing an AP compression type III injury (APC III) pelvic ring
      disruption and injury by approximating the inlet and outlet dimensions toward
      predisruption measurements. Such a degree of reduction suggests that the JETT
      device may be suitable in the acute setting for provisional pelvic stabilization.

PMID- 25399366
TI  - Prehospital and en route cricothyrotomy performed in the combat setting: a
      prospective, multicenter, observational study.
AB  - INTRODUCTION: Airway compromise is the third most common cause of potentially
      preventable combat death. Surgical cricothyrotomy is an infrequently performed
      but lifesaving airway intervention. There are limited published data on
      prehospital cricothyrotomy in civilian or military settings. Our aim was to
      prospectively describe the survival rate and complications associated with
      cricothyrotomy performed in the military prehospital and en route setting.
      METHODS: The Life-Saving Intervention (LSI) study is a prospective, institutional
      review board-approved, multicenter trial examining LSIs performed in the
      prehospital combat setting. We prospectively recorded LSIs performed on patients
      in theater who were transported to six combat hospitals. Trained site
      investigators evaluated patients on arrival and recorded demographics, vital
      signs, and LSIs performed. LSIs were predefined and include cricothyrotomies,
      chest tubes, intubations, tourniquets, and other procedures. From the large
      dataset, we analyzed patients who had a cricothyrotomy performed. Hospital
      outcomes were cross-referenced from the Department of Defense Trauma Registry.
      Descriptive statistics or Wilcoxon test (nonparametric) were used for data
      comparisons; statistical significance was set at p<.05. The primary outcome was
      success of prehospital and en route cricothyrotomy. RESULTS: Of the 1,927
      patients enrolled, 34 patients had a cricothyrotomy performed (1.8%). Median age
      was 24 years (interquartile range [IQR]: 22.5-25 years), 97% were men. Mechanisms
      of injury were blast (79%), penetrating (18%), and blunt force (3%), and 83% had
      major head, face, or neck injuries. Median Glasgow Coma Scale score (GCS) was 3
      (IQR: 3-7.5) and four patients had GCS higher than 8. Cricothyrotomy was
      successful in 82% of cases. Reasons for failure included left main stem
      intubation (n=1), subcutaneous passage (n=1), and unsuccessful attempt (n=4).
      Five patients had a prehospital basic airway intervention. Unsuccessful
      endotracheal intubation preceded 15% of cricothyrotomies. Of the 24 patients who
      had the provider type recorded, six had a cricothyrotomy by a combat medic (pre
      evacuation), and 18 by an evacuation helicopter medic. Combat-hospital outcome
      data were available for 26 patients, 13 (50%) of whom survived to discharge. The
      cricothyrotomy patients had more LSIs than noncricothyrotomy patients (four
      versus two LSIs per patient; p<.0011). CONCLUSION: In our prospective,
      multicenter study evaluating cricothyrotomy in combat, procedural success was
      higher than previously reported. In addition, the majority of cricothyrotomies
      were performed by the evacuation helicopter medic rather than the prehospital
      combat medic. Prehospital military medics should receive training in decision
      making and be provided with adjuncts to facilitate this lifesaving procedure.

PMID- 25399367
TI  - Evaluation of NuStatr, a Novel Nonimpregnated Hemostatic Dressing, Compared With
      Combat Gauze in Severe Traumatic Porcine Hemorrhage Model.
AB  - BACKGROUND: Uncontrolled hemorrhage remains one of the most challenging problems
      facing emergency medical professionals and a leading cause of traumatic death in
      both battlefield and civilian environments. Survival is determined by the ability
      to rapidly control hemorrhage. Several commercially available topical adjunct
      agents have been shown to be effective in controlling hemorrhage, and one, Combat
      Gauze (CG), is used regularly on the battlefield and for civilian applications.
      However, recent literature reviews have concluded that no ideal topical agent
      exists for all injuries and scenarios. The authors compared a novel
      nonimpregnated dressing composed of cellulose and silica, NuStat (NS), to CG in a
      lethal hemorrhagic groin injury. These dressings were selected for their
      commercial availability and design intended for control of massive hemorrhage.
      METHODS: A complex penetrating femoral artery groin injury was made using a 5.5mm
      vascular punch followed by 45 seconds of uncontrolled hemorrhage in 15 swine. The
      hemostatic dressings were randomized using a random sequence generator and then
      assigned to the animals. Three minutes of manual pressure was applied with each
      agent after the free bleed. Hextend bolus (500 mL) was subsequently rapidly
      infused using a standard pressure bag along with the addition of maintenance
      fluids to maintain blood pressure. Hemodynamic parameters were recorded every 10
      minutes and additionally at critical time points defined in the protocol. Primary
      end points included immediate hemostasis upon release of manual pressure (T0),
      hemostasis at 60 minutes, and rebleeding during the 60-minute observation period.
      RESULTS: NS was statistically superior to CG in a 5.5 mm traumatic hemorrhage
      model at T0 for immediate hemostasis (p=.0475), duration of application time
      (p=.0093), use of resuscitative fluids (p=.0042) and additional blood loss after
      application (p=.0385). NS and CG were statistically equivalent for hemostasis at
      60 minutes, rebleeding during the study, and the additional secondary metrics,
      although the trend indicated that in a larger sample size, NS could prove
      statistical superiority in selected categories. CONCLUSIONS: In this porcine
      model of uncontrolled hemorrhage, NS improved immediate hemorrhage control,
      stability, and use of fluid in a 60-minute severe porcine hemorrhage model. In
      this study, NS demonstrated equivalence to CG at achieving long-term hemostasis
      and the prevention of rebleed after application. NS was shown to be an
      efficacious choice for hemorrhage control in combat and civilian emergency
      medical service environments.

PMID- 25399368
TI  - Predicting When to Administer Blood Products During Tactical Aeromedical
      Evacuation: Evaluation of a US Model.
AB  - The administration of blood products to battlefield casualties in the prehospital
      arena has contributed significantly to the survival of critically injured
      patients in Afghanistan over the past 5 years. Given as part of an established
      military "chain of survival," blood product administration has represented a step
      change improvement in capability for both UK and US tactical aeromedical
      evacuation (TACEVAC) platforms. The authors explore current concepts, analyzing
      and exploring themes associated with early use of blood products (fresh frozen
      plasma [FFP] and red blood cells [RBCs]), and they compare and evaluate a US/UK
      study analyzing the differences and recommending future strategy. The subject
      matter expert (SME) consensus guidelines developed for use by the US Army Air
      Ambulance units commonly known as call sign "DUSTOFF." These TACEVAC assets in
      Afghanistan were validated in this retrospective study. Using statistical
      analysis, the authors were able to ascertain that the current DUSTOFF SME-derived
      guidelines offer a sensitivity of 63.04% and a specificity of 89.07%. By
      adjusting the indicators to include a single above-ankle amputation with a
      systolic blood pressure (SBP) less than 90 mmHg and pulse greater than 120/min,
      the sensitivity could be increased to 67.39% while maintaining the specificity at
      89.07%. In our data set, a single amputation above the ankle, in combination with
      an SBP of less than 100 mmHg and a pulse of greater than 120/min, increased the
      sensitivity to 76% but with a slight drop in specificity to 86%. Further study of
      military prehospital casualty data is under way to identify additional
      physiological parameters that will allow simple scoring tools in the remote
      setting to guide the administration of prehospital blood products.

PMID- 25399369
TI  - The use of dexamethasone in support of high-altitude ground operations and
      physical performance: review of the literature.
AB  - OBJECTIVE: Military Special Operators (SOs) are exposed environmental conditions
      that can alter judgment and physical performance: uneven terrain, dryness of
      ambient air, reduction of air density, and a diminished partial pressure of
      oxygen. The primary purpose of this review was to determine the medical efficacy
      of dexamethasone as an intervention for the prevention and treatment of high
      altitude illness. The secondary purpose was to determine its ability to maintain
      physical performance of SOs at high altitudes. METHODS: A search of the
      literature from 1970 to 2014 was performed, locating 61 relevant articles, with
      43 addressing the primary and secondary purposes of this literature review.
      CONCLUSIONS: The review indicates that dexamethasone is an effective prevention
      and treatment intervention for high-altitude illness. Commonly used dosages of
      either 2 mg every 6 hours or 4 mg every 12 hours can prevent high-altitude
      illnesses in adults. Currently in USSOCOM operations, there is an option to use 4
      mg every 6 hours (concurrently with acetazolamide 125 mg bid) if ascending
      rapidly to or above 11,500 ft without time for acclimatization. Researchers also
      determined that acute exposure to high altitude, even in asymptomatic subjects,
      resulted in small cognitive deficits that could be reversed with dexamethasone.
      Dexamethasone may also help improve cognition and maximal aerobic capacity in SOs
      who are susceptible to high-altitude pulmonary edema.

PMID- 25399370
TI  - Special Forces Medical Sergeants' perceptions and beliefs regarding their current
      medical sustainment program: implications for the field.
AB  - BACKGROUND: Special Forces Medical Sergeants (SFMS) are trained to provide trauma
      and medical care in support of military operations and diplomatic missions
      throughout the world with indirect physician oversight. This study assessed their
      perceptions of the current program designed to sustain their medical skills.
      METHODS: An Internet-based survey was developed using the constructs of the
      Theory of Reasoned Action/Planned Behavior and validated through survey best
      practices. RESULTS: Of the 334 respondents, 92.8% had deployed at least once as
      an SFMS. Respondents reported spending 4 hours per week sustaining their medical
      skills and were highly confident that they could perform their duties on a no
      notice deployment. On a 5-point, Likert-type response scale, SFMS felt that only
      slight change is needed to the Special Operations Medical Skills Sustainment
      Course (mean: 2.17; standard deviation [SD]: 1.05), while moderate change is
      needed to the Medical Proficiency Training (mean: 2.82; SD: 1.21) and nontrauma
      modules (mean: 3.02; SD: 1.22). Respondents desire a medical sustainment program
      that is provided by subject matter experts, involves actual patient care,
      incorporates new technology, uses hands-on simulation, and is always available.
      CONCLUSIONS: SFMS are challenged to sustain their medical skills in the current
      operational environment, and barriers to medical training should be minimized to
      facilitate sustainment training. Changes to the current medical sustainment
      program should incorporate operator-level perspectives to ensure acceptability
      and utility but must be balanced with organizational realities. Improving the
      medical sustainment program will prepare SFMS for the challenges of future
      missions.

PMID- 25399371
TI  - A Call for Innovation: Reflective Practices and Clinical Curricula of US Army
      Special Operations Forces Medics.
AB  - BACKGROUND: Special Operations Forces (SOF) medics have written and published
      numerous practice reflections that intricately describe their practice
      environments, clinical dilemmas, and suggestions for teaching and practice. The
      lack of translation of SOF medics experiential evidence to their curriculum has
      created a gap in evidence-based curriculum development. This study analyzed SOF
      medics learning and practice patterns and compared it to the evidence in the
      interdisciplinary clinical literature. After framing the problem, the literature
      was reviewed to determine appropriate tools by which perceptions and attitudes
      toward reflection-centered curricula could be measured. METHODS: A recognizable
      practice reflection was extracted from the published SOF clinical literature and
      presented in writing to self-identified SOF medics and medic instructors via a
      descriptive crossover design, to ensure possible biases were mitigated. To
      measure SOF medics perceptions of reflection-based curricula, the Dundee Ready
      Education Environment Measure survey instrument was used, as it has validated
      psychometric properties and is used worldwide. RESULTS: SOF medics averaged
      scores of perceptions of their medic education indicated positive but not
      completely statistically significant preferences toward reflection-based
      curricula over traditional curriculum. KEYWORDS: Special Operations, medics,
      reflective practice, curricula BACKGROUND Special Operations Forces (SOF) medics
      practice in environments that are violent, austere, clandestine, and far removed
      from definitive hospital facilities. What was true almost 20 years ago?". . .
      academic demands of [Special Forces medic training] are roughly equivalent to
      those of an upper-level undergraduate curriculum in science or perhaps to those
      of first year medical school"?is even more challenging today. During this study,
      medics, physicians, and educators within the SOF medical community publicly and
      privately (ergo, names were redacted) expressed the need for curricular changes
      to teach SOF medics about the worst of clinical scenarios, such as situations in
      which evacuation of critically injured Soldiers to higher echelons of care is not
      possible or is prolonged, due to combat engagements or other complications. These
      experts consistently describe the need for curriculum derived from experienced
      medics practices, to guide force-wide knowledge acquisition and augment student
      medics professional development. Given the investigator?s clinical familiarity
      with SOF medics practice and evidence, senior, enlisted SOF medics and SOF medic
      instructors proposed that a doctoral-prepared nurse, whose clinical specialty was
      trauma, could spearhead academic focus and publication on the experiences and
      curriculum of SOF medics.

PMID- 25399372
TI  - Point prevalence survey for tick-borne pathogens in military working dogs,
      shelter animals, and pet populations in northern Colombia.
AB  - BACKGROUND: Based on the high tick-borne pathogen results from a 2011
      surveillance study in three Colombian cities, an in-depth point prevalence survey
      was conducted to determine the seroprevalence of tick-borne pathogens at a
      specific point in time in 70 working dogs, 101 shelter dogs, and 47 client-owned
      dogs in Barranquilla, Colombia. RESULTS: Of the 218 serum samples, 163 (74%) were
      positive for Ehrlichia canis and 116 (53%) for Anaplasma platys. Exposure to tick
      borne pathogens was highest in shelter and working dogs where more than 90% of
      the samples were seropositive or positive on polymerase chain reaction for one or
      more organisms as compared to 51% in client-owned animals. CONCLUSION:
      Surveillance for exposure to tick-borne pathogens provides vital information
      necessary to protect and conserve the health of local humans and animals,
      deployed military service members, and working dogs in various parts of the
      world. This study and resultant data demonstrate the value of following a broad
      based surveillance study with a more specific, focused analysis in an area of
      concern. This area?s high levels of exposure warrant emphasis by medical planners
      and advisors on precautionary measures for military dogs, Special Operations
      Forces personnel, and the local public.

PMID- 25399373
TI  - Review of Canine Deaths While in Service in US Civilian Law Enforcement (2002
      2012).
AB  - BACKGROUND: Working dogs have been proven effective in multiple military and law
      enforcement applications. Similar to their human counterparts, understanding
      mortality while still in service can help improve treatment of injuries, and
      improve equipment and training, to potentially reduce deaths. This is a
      retrospective study to characterize mortality of working dogs used in civilian
      law enforcement. METHODS: Reported causes of death were gathered from two working
      dog and law enforcement officer memorial websites. RESULTS: Of the 867 civilian
      law enforcement dogs reported to these memorial websites from 2002 to 2012 with
      reported causes of death while in service, the deaths of 318 were categorized as
      traumatic. The leading reported causes of traumatic death or euthanasia include
      trauma as a result of a vehicle strike, 25.8% (n=82); heatstroke, 24.8% (n=79);
      and penetrating ballistic trauma, 23.0% (n=73). CONCLUSION: Although the
      information gathered was from online sources, this study casts some light on the
      risks that civilian law enforcement dogs undergo as part of the tasks to which
      they are assigned. These data underscore the need for a comprehensive database
      for this specialized population of working dogs to provide the robust, reliable
      data needed to develop prevention and treatment strategies for this valuable
      resource.

PMID- 25399374
TI  - Pilot ejection, parachute, and helicopter crash injuries.
AB  - USAF Pararescuemen (PJs) respond to downed aircrew as a fundamental mission for
      personnel recovery (PR), one of the Air Force's core functions. In addition to
      responding to these in Military settings, the PJs from the 212 Rescue Squadron
      routinely respond to small plane crashes in remote regions of Alaska. While there
      is a paucity of information on the latter, there have been articles detailing
      injuries sustained from helicopter crashes and while ejecting or parachuting from
      fixed wing aircraft. The following represents a new chapter added to the
      Pararescue Medical Operations Handbook, Sixth Edition (2014, editors Matt Wolf,
      MD, and Stephen Rush, MD, in press). It was designed to be a quick reference for
      PJs and their Special Operations flight surgeons to help with understanding of
      mechanism of injury with regard to pilot ejection, parachute, and helicopter
      accident injuries. It outlines the nature of the injuries sustained in such
      mishaps and provides an epidemiologic framework from which to approach the
      problem.

PMID- 25399375
TI  - Evaluation of commercially available traction splints for battlefield use.

PMID- 25399376
TI  - Response to Mr. Lee's letter to the editor.

PMID- 25399377
TI  - Performance psychology as a key component of human performance optimization.
AB  - The degree of psychological fitness will ultimately impact mission outcomes, so
      approaches to enhancing it are critical. Performance psychology is one important
      aspect of psychological fitness that fits into the holistic model of human
      performance optimization. This article delves into one component of performance
      psychology: how mental skill training can be applied to improve performance on
      mission-related tasks. Mental skills training provides added internal resources
      to help meet the extraordinary external demands that Special Operations Forces
      personnel can face. Relevance in terms of the demand-resource model and the
      positive psychology concept of flow are explained. The application of two
      specific mental skills--executing a goal-setting process and using mental imagery
      to rehearse technical, tactical, and strategic tasks--will be discussed by using
      the example of how to enhance performance when entering and clearing rooms.

PMID- 25399378
TI  - Force health protection support following a natural disaster: the 227th Medical
      Detachment's role in response to Superstorm Sandy.
AB  - On 3 November 2012, in the wake of Superstorm Sandy, the 227th Preventive
      Medicine Medical Detachment deployed to support relief operations in New Jersey
      and New York State. The unit was on the severe weather support mission (SWRF) and
      ordered to provide preventive medicine support to relief personnel within the
      affected area. In addition, teams from the 227th conducted environmental
      surveillance in the two-state region where Army Corps of Engineers were pumping
      floodwaters from affected neighborhoods. The 227th rapid deployment highlights
      the complexities associated with defense support to civil authorities and
      provides excellent teaching points that may enhance units expeditionary posture,
      regardless of mission. 

PMID- 25399379
TI  - Bites, stings, and rigors: clinical considerations in African operations.
AB  - The natural health threats in Africa pose daunting clinical challenges for any
      provider, as evidenced by the current Ebola epidemic in West Africa, but the
      threat is multiplied for the Special Operations provider on the continent who
      faces these challenges with limited resources and the tyranny of distance. The
      majority of operationally significant health risks can be mitigated by strict
      adherence to a comprehensive force health protection plan. The simplest, yet most
      effective, technique for preventing mosquito-borne diseases is the prevention of
      mosquito bites with repellent, bed nets, and appropriate clothing in addition to
      chemoprophylaxis. Some of the more likely or lethal infectious diseases
      encountered on the continent include malaria, Chikungunya, dengue, human
      immunodeficiency virus, and Ebola. Venomous snakes pose a particular challenge
      since the treatment can be as deadly as the injury. Providers supporting African
      operations should educate themselves on the clinical characteristics of possible
      envenomations in their area while promoting snake avoidance as the primary
      mitigation measure. To succeed in Africa, the Special Operations provider must
      consider how to meet these challenges in an environment where there may not be
      reliable evacuation, hospitalization, or logistics channels. 

PMID- 25399380
TI  - Erythema nodosum.
AB  - An active duty female Sailor reports to your clinic complaining of tender nodules
      to her legs beginning 1.5 weeks ago. She is diagnosed with erythema nodosum (EN),
      a painful disorder of the subcutaneous fat that is usually self-limited but may
      be a clue to an additional underlying medical diagnosis. This article reviews the
      pathophysiology, causes, course, diagnosis, and management of EN. 

PMID- 25399381
TI  - Sore throat.

PMID- 25399382
TI  - Chikungunya.
AB  - Chikungunya is a rapidly emerging infectious disease caused by a virus of the
      genus Alphavirus, family Togaviridae. Most commonly, patients have an acute onset
      of fever with often debilitating symmetric joint discomfort that can relapse
      months after the initial infection. This infection is typically transmitted by
      the bite of an infected Aedes aegypti or Aedes albopictus mosquito, vectors that
      also transmit dengue and yellow fever. Special Operations Forces Medical
      Providers should be aware of this disease, which is currently being diagnosed
      worldwide. 

PMID- 25399383
TI  - Injuries and injury prevention during foot marching.
AB  - Since the beginning of recorded history, Soldiers have carried arms and equipment
      on their bodies. More recently, loads have substantially increased, driven by
      improvements in weapons technology and personal protection. As Soldier loads
      increase, there are increases in energy cost, altered gait mechanics, increased
      stress on the musculoskeletal system, and more rapid fatigue, factors that may
      increase the risk of injury. Common injuries and symptoms experienced by Soldiers
      on load-carriage missions include foot blisters, metatarsalgia, knee problems,
      and back problems. This article discusses these problems, providing diagnoses,
      injury mechanisms, and preventive measures. In general, lighter loads, improving
      load distribution, using appropriate physical training, selecting proper
      equipment, and using specific prevention techniques will facilitate load carriage
      and provide Special Operations Forces with a higher probability of mission
      success. 

PMID- 25399384
TI  - Management of open chest wounds in tactical emergency casualty care: application
      of vented versus nonvented chest seals.
AB  - The 2014 midyear, full meeting of the Committee for Tactical Emergency Combat
      Care (C-TECC) was hosted by the Johns Hopkins University Center for Law
      Enforcement Medicine on June 9 and 10 in Baltimore, Maryland. As the C-TECC
      guidelines are increasingly recognized as the best-practice recommendations for
      civilian, high-threat, prehospital trauma response, a focused guidelines
      discussion occurred to develop best-practice recommendations for the management
      of open chest wounds, specifically regarding the application of vented and
      nonvented chest seals. 

PMID- 25399385
TI  - Distinguishing gouty arthritis from calcium pyrophosphate disease and other
      arthritides.
AB  - OBJECTIVE: Differentiating gout, calcium pyrophosphate deposition disease (CPPD),
      and non-crystal-related inflammatory arthropathies (non-CRA) is essential but
      often clinically impossible. The sonographic double contour (DC) sign may have
      good specificity for gout in highly specialized centers, but it can be
      challenging to use it to distinguish gout from cartilage hyperenhancements in
      CPPD. We evaluated the diagnostic value of the DC sign alone and in combination
      with Doppler signals and uric acid (UA) levels in patients with acute arthritis.
      METHODS: We retrospectively investigated 225 acutely inflamed joints and
      documented the presence of DC, Doppler hypervascularization, and serum UA (SUA)
      levels. All patients underwent synovial fluid (SF) analysis. Sensitivity,
      specificity, and positive predictive values were calculated, and correlation
      analyses and a binary regression model were used to investigate their diagnostic
      values. RESULTS: The sensitivity of DC sign for crystalline arthritides was 85%
      and specificity 80%. Its specificity for gout was 64%, for CPPD 52%. In contrast
      to non-CRA hypervascularization, degree 2 and 3 Doppler signals were highly
      associated with gout and less with CPPD (p < 0.01). The combination of DC sign
      with hypervascularization and elevated UA levels increased specificity for gout
      to more than 90% and resulted in a 7-fold increase of the likelihood of diagnosis
      of gout (p < 0.01), but with a loss of sensitivity (42%). CONCLUSION: The DC sign
      alone is suitable for predicting crystal-related arthropathies, but it cannot
      reliably distinguish gout from CPPD in everyday clinical routine. Combining
      hypervascularization and SUA levels increases the diagnostic value, leading us to
      propose a diagnostic algorithm.

PMID- 25399386
TI  - Clinical features and radiological findings in large vessel vasculitis: are
      Takayasu arteritis and giant cell arteritis 2 different diseases or a single
      entity?
AB  - OBJECTIVE: Takayasu arteritis (TAK) and giant cell arteritis (GCA) are 2 major
      variants of large vessel vasculitis (LVV). The frequent involvement of large
      vessels in GCA has raised the possibility that TAK and GCA should be regarded as
      1 disease. By detailed phenotyping of a single-center cohort, we aimed to define
      the differences between TAK and GCA. METHODS: Forty-five patients (23 TAK, 22
      GCA) were identified. Baseline characteristics, clinical symptoms, laboratory
      data, enhanced computed tomography/magnetic resonance imaging, treatments, and
      clinical courses were retrospectively assessed with descriptive statistics. In
      addition, latent class analysis of the 45 patients was performed to explore
      phenotypic differences. RESULTS: Patients with GCA had more frequent headache (p
      < 0.01), higher C-reactive protein levels (p = 0.01), and higher erythrocyte
      sedimentation rates (p = 0.03) than did patients with TAK at diagnosis. With the
      exception of subdiaphragmatic lesions, the distributions of vessel lesions were
      not different between TAK and GCA. However, focusing on subclavian and carotid
      arteries, long tapered-type stenotic lesions were more frequent in GCA than in
      TAK (p < 0.01). The proportion of patients without relapse was higher in GCA
      (60%) than in TAK (22%, p = 0.01). Latent class analysis also divided patients
      with LVV into 2 separate groups consistent with TAK and GCA. CONCLUSION: The
      differences observed in clinical symptoms, inflammatory markers, radiological
      findings, and clinical courses suggested that TAK and GCA were 2 different
      diseases. Latent class analysis supported these results. The shape of stenotic
      lesions in the subclavian and carotid arteries is a useful discriminator between
      TAK and GCA.

PMID- 25399387
TI  - Criterion-concurrent validity of spinal mobility tests in ankylosing spondylitis:
      a systematic review of the literature.
AB  - OBJECTIVE: To examine the level of evidence for criterion-concurrent validity of
      spinal mobility assessments in patients with ankylosing spondylitis (AS).
      METHODS: Guidelines proposed in the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses were used to undertake a search strategy involving 3
      sets of keywords: accura*, truth, valid*; ankylosing spondylitis,
      spondyloarthritis, spondyloarthropathy, spondylarthritis; mobility, spinal
      measure*, (a further 16 keywords with similar meaning were used). Seven databases
      were searched from their inception to February 2014: AMED, Embase, ProQuest,
      PubMed, Science Direct, Scopus, and Web of Science. The Quality Assessment of
      Diagnostic Accuracy Studies (with modifications) was used to assess the quality
      of articles reviewed. An article was considered high quality when it received
      "yes" in at least 9 of the 13 items. RESULTS: From the 741 records initially
      identified, 10 articles were retained for our systematic review. Only 1 article
      was classified as high quality, and this article suggests that 3 variants of the
      Schober test (original, modified, and modified-modified) poorly reflect lumbar
      range of motion where radiographs were used as the reference standard.
      CONCLUSION: The level of evidence considering criterion-concurrent validity of
      clinical tests used to assess spinal mobility in patients with AS is low.
      Clinicians should be aware that current practice when measuring spinal mobility
      in AS may not accurately reflect true spinal mobility.

PMID- 25399389
TI  - Classification and diagnosis of axial spondyloarthritis--what is the clinically
      relevant difference?
AB  - OBJECTIVE: The Assessment of Spondyloarthritis international Society (ASAS)
      classification criteria for axial spondyloarthritis (axSpA) have added
      nonradiographic axSpA (nr-axSpA) to the classic ankylosing spondylitis (AS) as
      defined by the modified New York criteria. However, some confusion remains about
      differences between classification and diagnosis of axSpA. Our objective was to
      analyze differences between classification and diagnostic criteria by discussing
      each feature of the classification criteria based on real cases. METHODS: The
      clinical features of the ASAS classification criteria were evaluated in relation
      to their significance for an expert diagnosis of axSpA. Twenty cases referred to
      our tertiary center outpatient clinic were selected because of an incorrect
      diagnosis of axSpA: 10 cases in which axSpA had been excluded initially because
      the classification criteria were not fulfilled, and 10 patients who had been
      previously diagnosed with axSpA because the classification criteria were
      fulfilled. Upon reevaluation, the former were diagnosed with axSpA while the
      latter had other diseases. RESULTS: All items that are part of the classification
      criteria show some variability related to their relevance for a diagnosis of
      axSpA. There are clinical features suggestive of axSpA that are not part of the
      classification criteria. Misinterpretation of imaging procedures contributed to
      false-positive results. Rarely, other diseases may mimic axSpA. CONCLUSION:
      Because the sensitivity and specificity of the axSpA classification criteria have
      been around 80% in clinical trials, some false-positive and false-negative cases
      were expected. It is hoped that their detailed description and discussion will
      help to increase the understanding of diagnosing axSpA in relation to the ASAS
      classification criteria.

PMID- 25399388
TI  - Does socioeconomic status affect outcomes in early inflammatory arthritis? Data
      from a canadian multisite suspected rheumatoid arthritis inception cohort.
AB  - OBJECTIVE: To assess the effect of socioeconomic status (SES) on outcomes in
      patients with early inflammatory arthritis, using data from the Canadian Early
      Arthritis Cohort (CATCH) study. METHODS: In an incident cohort, 2023 patients
      were recruited, and allocated to low SES or high SES groups based on education
      and income. Outcomes at baseline and 12 months were analyzed in relation to SES
      including the 28-joint Disease Activity Score (DAS28), Simplified Disease
      Activity Index (SDAI), pain, patient's global assessment scale (PtGA), the Health
      Assessment Questionnaire-Disability Index (HAQ-DI), and the SF12-v2 Health
      Survey, using the ANOVA, chi-squared test, and regression analyses. RESULTS: The
      CATCH population had 43% with high school education or less and 37% in the low
      income group (< 50,000 Can$ per annum household income). The low-education group
      had higher DAS28 at baseline (p = 0.045), becoming nonsignificant at 12 months
      and lower physical component score on SF12-v2 at baseline (p = 0.022). Patients
      in the low-income group presented with higher HAQ-DI (p = 0.017), pain (p =
      0.035), PtGA (p = 0.004), and SDAI (p = 0.022). Low-income versus high-income
      groups were associated with an OR above the median for HAQ-DI (1.20; 95% CI 1.00
      1.45), PtGA (1.27; 95% CI 1.06-1.53), and SDAI (1.25; 95% CI 1.02-1.52) at
      baseline. The association with low income persisted at 12 months for HAQ-DI (OR
      1.30; 95% CI 1.02-1.67), but not for other variables. CONCLUSION: Low SES was
      initially associated with higher disease activity, pain, and PtGA, and poorer
      function. At 1 year, outcomes were similar to those with high SES, with the
      exception of HAQ-DI.

PMID- 25399390
TI  - Prevalence of TNF-alpha blocker immunogenicity in psoriatic arthritis.
AB  - OBJECTIVE: The longterm use of tumor necrosis factor (TNF)-alpha blockers is
      limited by the formation of neutralizing antibodies. To the best of our
      knowledge, immunogenicity in psoriatic arthritis (PsA) has not been investigated
      in depth. Our objective was to evaluate the prevalence and significance of TNF
      alpha blocker immunogenicity in PsA. METHODS: Consecutive patients with PsA
      treated with either infliximab (IFX), adalimumab (ADA), or etanercept (ETN) > 3
      months participated in our cross-sectional study. Their demographic and clinical
      characteristics, skin and joint disease activity, and records of use of
      methotrexate (MTX) and other medications were collected. Drug levels (ELISA) and
      antidrug antibodies (ADAb; Bridging ELISA) were evaluated before the next
      injection or infusion. RESULTS: A total of 93 patients with PsA were recruited
      (48 receiving ADA, 24 IFX, and 21 ETN), with a mean age of 53 years (range 21-83
      yrs), composed of 53% women. One-fourth of the patients were concomitantly
      treated with MTX. Altogether, 77% of the patients demonstrated therapeutic drug
      levels. High levels of ADAb were found in 29% of patients taking ADA, 21% taking
      IFX, and 0% taking ETN. ADAb significantly correlated with lower drug levels,
      higher 28-joint Disease Activity Scores, and higher global assessments. MTX use
      correlated significantly with a lower prevalence of ADAb. CONCLUSION: Significant
      levels of ADAb were present in up to 29% of patients with PsA treated with ADA or
      IFX. ADAb clearly correlated with low therapeutic drug levels and higher disease
      activity variables. The use of MTX significantly decreased ADAb prevalence, and
      its use should be strongly considered in combination with TNF-alpha blocker
      antibodies in patients with PsA.

PMID- 25399391
TI  - Cost of illness and determinants of costs among patients with gout.
AB  - OBJECTIVE: To estimate costs of illness in a cross-sectional cohort of patients
      with gout attending an outpatient rheumatology clinic, and to evaluate which
      factors contribute to higher costs. METHODS: Altogether, 126 patients with gout
      were clinically assessed. They completed a series of questionnaires. Health
      resource use was collected using a self-report questionnaire that was cross
      checked with the electronic patient file. Productivity loss was assessed by the
      Work Productivity and Activity Impairment Questionnaire, addressing absenteeism
      and presenteeism. Resource use and productivity loss were valued by real costs,
      and annual costs per patient were calculated. Factors contributing to incurring
      costs above the median were explored using logistic univariable and multivariable
      regression analysis. RESULTS: Mean (median) annual direct costs of gout were
      ?5647 (?1148) per patient. Total costs increased to ?6914 (?1279) or ?10,894
      (?1840) per patient per year when adding cost for absenteeism or both absenteeism
      and presenteeism, respectively. Factors independently associated with high direct
      and high indirect costs were a positive history of cardiovascular disease,
      functional limitations, and female sex. In addition, pain, gout concerns, and
      unmet gout treatment needs were associated with high direct costs. CONCLUSION:
      The direct and indirect costs-of-illness of gout are primarily associated with
      cardiovascular disease, functional limitations, and female sex.

PMID- 25399392
TI  - The circulating cell-free microRNA profile in systemic sclerosis is distinct from
      both healthy controls and systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the expression profile of cell-free circulating microRNA
      (miRNA) in systemic sclerosis (SSc), healthy controls (HC), and systemic lupus
      erythematosus (SLE). METHODS: Total RNA was purified from plasma and 45
      different, mature miRNA were measured using quantitative PCR assays after reverse
      transcription. Samples (n = 189) were from patients with SSc (n = 120), SLE (n =
      29), and from HC (n = 40). Expression data were clustered by principal components
      analysis, and diagnostically specific miRNA profiles were developed by leave-one
      out cross-validation. Diagnostic probability scores were derived from stepwise
      logistic regression. RESULTS: Thirty-seven miRNA specificities were consistently
      detected and 26 of these were unaffected by SSc sample age and present in more
      than two-thirds of SSc samples. SSc cases showed a distinct expression profile
      with 14/26 miRNA significantly decreased (false discovery rate < 0.05) and 5/26
      increased compared with HC. A 21-miRNA classifier gave optimum accuracy (80%) for
      discriminating SSc from both HC and SLE. The discrimination between HC and SSc
      (95% accuracy) was strongly driven by miRNA of the 17 ~ 92 cluster and by miR-16,
      -223, and -638, while SLE and SSc differed mainly in the expression of miR-142
      3p, -150, -223, and -638. Except for a weak correlation between anti-Scl-70 and
      miR-638 (p = 0.048), there were no correlations with other patient variables.
      CONCLUSION: Circulating miRNA profiles are characteristic for SSc compared with
      both HC and SLE cases. Some of the predicted targets of the differentially
      regulated miRNA are of relevance for transforming growth factor-beta signaling
      and fibrosis, but need to be validated in independent studies.

PMID- 25399393
TI  - Association between nailfold capillaroscopy findings and pulmonary function tests
      in patients with systemic sclerosis.
AB  - OBJECTIVE: To determine whether there is an association between different
      capillaroscopic findings and pulmonary function tests in systemic sclerosis
      (SSc). METHODS: We did a retrospective observational study in a cohort of
      patients with SSc and early SSc. Patients with at least 1 nailfold
      videocapillaroscopy (NVC) magnified 120* were included. Pathological findings
      were giant capillaries, angiogenesis, and density loss. Findings were compared
      with lung function values: percent expected value of forced vital capacity (FVC),
      DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and
      the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma
      renal crisis, and/or pulmonary hypertension (PH). RESULTS: Of 136 patients with
      SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%,
      and 17.2%, respectively. Data analysis showed that patients with density loss had
      worse FVC% (86.91 +/- 19.42 vs 101.13 +/- 16.06, p < 0.01) and DLCO% (71.43 +/-
      21.19 vs 85.9 +/- 19.81, p < 0.01) compared to those without. CONCLUSION:
      Patients with loss of density present worse FVC and DLCO values. Prospective
      studies are warranted to determine whether NVC is useful for studying pulmonary
      function in SSc.

PMID- 25399394
TI  - Improving psychosexual knowledge in adolescents with autism spectrum disorder:
      pilot of the tackling teenage training program.
AB  - Previous studies have shown that psychosexual functioning in adolescents with
      autism spectrum disorder (ASD) is hampered and emphasize the need for a
      specialized training program tailored to their needs. Therefore, an individual
      training program was developed; the Tackling Teenage Training (TTT) program. The
      current pilot study systematically evaluated whether psychosexual knowledge
      increased after taking part in the TTT program, using a pre- and post-training
      design in 30 adolescents with ASD (77 % male, mean age = 14.80 years, mean
      intelligence = 96.96). Psychosexual knowledge increased significantly (pre
      training total score: M = 25.74, SD = 6.20; post-training total score: M = 33.52
      (SD = 2.78); F(1,29) = 65.20, p < .001). The TTT program may be useful to improve
      psychosexual knowledge and functioning in adolescents with ASD, yet these
      findings are preliminary, and a more elaborate controlled trial is needed.

PMID- 25399395
TI  - Improved survival after out-of-hospital cardiac arrest and use of automated
      external defibrillators.
AB  - BACKGROUND: In recent years, a wider use of automated external defibrillators
      (AEDs) to treat out-of-hospital cardiac arrest was advocated in The Netherlands.
      We aimed to establish whether survival with favorable neurologic outcome after
      out-of-hospital cardiac arrest has significantly increased, and, if so, whether
      this is attributable to AED use. METHODS AND RESULTS: We performed a population
      based cohort study, including patients with out-of-hospital cardiac arrest from
      cardiac causes between 2006 and 2012, excluding emergency medical service
      witnessed arrests. We determined survival status at each stage (to emergency
      department, to admission, and to discharge) and examined temporal trends using
      logistic regression analysis with year of resuscitation as an independent
      variable. By adding each covariable subsequently to the regression model, we
      investigated their impact on the odds ratio of year of resuscitation. Analyses
      were performed according to initial rhythm (shockable versus nonshockable) and
      AED use. Rates of survival with favorable neurologic outcome after out-of
      hospital cardiac arrest increased significantly (N=6133, 16.2% to 19.7%; P for
      trend=0.021), although solely in patients presenting with a shockable initial
      rhythm (N=2823; 29.1% to 41.4%; P for trend<0.001). In this group, survival
      increased at each stage but was strongest in the prehospital phase (odds ratio,
      1.11 [95% CI, 1.06-1.16]). Rates of AED use almost tripled during the study
      period (21.4% to 59.3%; P for trend <0.001), thereby decreasing time from
      emergency call to defibrillation-device connection (median, 9.9 to 8.0 minutes;
      P<0.001). AED use statistically explained increased survival with favorable
      neurologic outcome by decreasing the odds ratio of year of resuscitation to a
      nonsignificant 1.04. CONCLUSIONS: Increased AED use is associated with increased
      survival in patients with a shockable initial rhythm. We recommend continuous
      efforts to introduce or extend AED programs.

PMID- 25399396
TI  - Recent trends in survival from out-of-hospital cardiac arrest in the United
      States.
AB  - BACKGROUND: Despite intensive efforts over many years, the United States has made
      limited progress in improving rates of survival from out-of-hospital cardiac
      arrest. Recently, national organizations, such as the American Heart Association,
      have focused on promoting bystander cardiopulmonary resuscitation, use of
      automated external defibrillators, and other performance improvement efforts.
      METHODS AND RESULTS: Using the Cardiac Arrest Registry to Enhance Survival
      (CARES), a prospective clinical registry, we identified 70 027 U.S. patients who
      experienced an out-of-hospital cardiac arrest between October 2005 and December
      2012. Using multilevel Poisson regression, we examined temporal trends in risk
      adjusted survival. After adjusting for patient and cardiac arrest
      characteristics, risk-adjusted rates of out-of-hospital cardiac arrest survival
      increased from 5.7% in the reference period of 2005 to 2006 to 7.2% in 2008
      (adjusted risk ratio, 1.27; 95% confidence interval, 1.12-1.43; P<0.001).
      Survival improved more modestly to 8.3% in 2012 (adjusted risk ratio, 1.47; 95%
      confidence interval, 1.26-1.70; P<0.001). This improvement in survival occurred
      in both shockable and nonshockable arrest rhythms (P for interaction=0.22) and
      was also accompanied by better neurological outcomes among survivors (P for
      trend=0.01). Improved survival was attributable to both higher rates of
      prehospital survival, where risk-adjusted rates increased from 14.3% in 2005 to
      2006 to 20.8% in 2012 (P for trend<0.001), and in-hospital survival (P for
      trend=0.015). Rates of bystander cardiopulmonary resuscitation and automated
      external defibrillator use modestly increased during the study period and partly
      accounted for prehospital survival trends. CONCLUSIONS: Data drawn from a large
      subset of U.S communities suggest that rates of survival from out-of-hospital
      cardiac arrest have improved among sites participating in a performance
      improvement registry.

PMID- 25399397
TI  - Trends in short- and long-term survival among out-of-hospital cardiac arrest
      patients alive at hospital arrival.
AB  - BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is associated with a poor
      prognosis and poses a significant burden to the healthcare system, but few
      studies have evaluated whether OHCA incidence and survival have changed over
      time. METHODS AND RESULTS: A population-based cohort study was conducted,
      including 34 291 OHCA patients >20 years of age who were transported alive to the
      emergency department of an acute-care hospital from April 1, 2002, to March 31,
      2012, in Ontario, Canada. Patients with life-threatening trauma and those who
      died before hospital arrival were excluded. The overall age- and sex-standardized
      incidence of OHCA patients who were transported alive was 36 cases per 100 000
      persons and did not significantly change over the study period. Cardiac risk
      factor prevalence increased significantly, whereas the rate of most
      cardiovascular conditions decreased significantly. The 30-day survival improved
      from 9.4% in 2002 to 13.6% in 2011; 1-year survival improved from 7.7% to 11.8%
      (P<0.001). Patients hospitalized in 2011 were significantly more likely to
      survive 30 days (adjusted odds ratio, 1.47 [95% CI, 1.22-1.77]) and 1 year
      (adjusted odds ratio, 1.55 [95% CI, 1.27-1.91]) compared with 2002. A significant
      interaction between temporal trends in survival improvement and age group was
      observed in which the improvement in survival was largest in the youngest age
      groups. CONCLUSIONS: OHCA patients who were transported alive are increasingly
      likely to have cardiovascular risk factors but less likely to have previous
      cardiovascular conditions. The overall incidence of OHCA patients transported to
      hospital alive did not change over the past decade. Short- and longer-term
      survival after OHCA has substantially improved, with younger patients
      experiencing the greatest improvement.

PMID- 25399398
TI  - Treatment for out-of-hospital cardiac arrest: is the glass half empty or half
      full?

PMID- 25399399
TI  - Detection and molecular characterization of bovine leukemia virus in Philippine
      cattle.
AB  - Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis,
      which is the most common neoplastic disease of cattle. BLV infects cattle
      worldwide, imposing a severe economic impact on the dairy cattle industry.
      However, there are no comprehensive studies on the distribution of BLV in the
      Philippines, and the genetic characteristics of Philippine BLV strains are
      unknown. Therefore, the aim of this study was to detect BLV infections in the
      Philippines and determined their genetic variability. Blood samples were obtained
      from 1116 cattle from different farms on five Philippine islands, and BLV
      provirus was detected by BLV-CoCoMo-qPCR-2 and nested PCR targeting BLV long
      terminal repeats. Out of 1116 samples, 108 (9.7 %) and 54 (4.8 %) were positive
      for BLV provirus, as determined by BLV-CoCoMo-qPCR-2 and nested PCR,
      respectively. Of the five islands, Luzon Island showed the highest prevalence of
      BLV infection (23.1 %). Partial env gp51 genes from 43 samples, which were
      positive for BLV provirus by both methods, were sequenced for phylogenetic
      analysis. Phylogenetic analysis based on a 423-bp fragment of the env gene
      revealed that Philippine BLV strains clustered into either genotype 1 or genotype
      6. Substitutions were mainly found in antigenic determinants, such as the CD4(+)
      T-cell epitope, the CD8(+) T-cell epitope, the second neutralizing domain, B and
      E epitopes, and these substitutions varied according to genotype. This study
      provides comprehensive information regarding BLV infection levels in the
      Philippines and documents the presence of two BLV genotypes, genotypes 1 and 6,
      in this population.

PMID- 25399400
TI  - Assessment of coliphage surrogates for testing drinking water treatment devices.
AB  - Test protocols have been developed by the United States Environmental Protection
      Agency (USEPA) and the World Health Organization (WHO) to test water treatment
      devices/systems that are used at the individual and home levels to ensure the
      removal of waterborne viruses. The goal of this study was to assess if coliphage
      surrogates could be used in this testing in place of the currently required use
      of animal or human enteric viruses. Five different coliphages (MS-2, PRD1, PhiX
      174, Qbeta, and fr) were compared to the removal of poliovirus type 1 (LSc-2ab)
      by eight different water treatment devices/systems using a general case and a
      challenge case (high organic load, dissolved solids, and turbidity) test water as
      defined by the USEPA. The performance of the units was rated as a pass/fail based
      on a 4 log removal/inactivation of the viruses. In all cases, a failure or a pass
      of the units/system for poliovirus also corresponded to a pass/fail by all of the
      coliphages. In summary, in using pass/fail criteria as recommended under USEPA
      guidelines for testing water treatment device/systems, the use of coliphages
      should be considered as an alternative to reduce cost and time of testing such
      devices/systems.

PMID- 25399401
TI  - Cytomegalovirus proctitis mimicking rectal cancer in an immunocompetent elderly
      patient: a case report.
AB  - BACKGROUND: Cytomegalovirus infection is associated with significant morbidity
      and mortality in immunocompromised patients, but its impact on immunocompetent
      patients is still poorly understood. Furthermore, there is increasing evidence
      implying that chronic infection may contribute to a heightened cardiovascular
      risk. CASE PRESENTATION: We describe the case of incidental diagnosis of
      Cytomegalovirus proctitis in an immune-competent white British elderly gentleman,
      admitted following a stroke and investigated for rectal cancer following the
      development of bloody diarrhoea and persistent systemic inflammatory response.
      CONCLUSION: This raised some several interesting points; firstly that we must
      revise our approach to investigating the immunocompetent elderly patient,
      secondly, could chronic Cytomegalovirus infection have contributed to the
      presentation of stroke in this patient and lastly what are the existing evidence
      for treatment in this population? We use this opportunity to try and address some
      of these questions and feel that this would be of benefit to the wider
      audience.We discuss the risk factors for disease in immune-competent patients and
      also a brief overview of the benefits of treatment in this population.

PMID- 25399402
TI  - Descriptive characterization of the 2010 cholera outbreak in Nigeria.
AB  - BACKGROUND: In 2010, 18 States of Nigeria reported cholera outbreaks with a total
      of 41,787 cases including 1,716 deaths (case-fatality rate [CFR]: 4.1%). This
      exceeded the mean overall CFR of 2.4% reported in Africa from 2000-2005 and the
      WHO acceptable rate of 1%. We conducted a descriptive analysis of the 2010
      cholera outbreak to determine its epidemiological and spatio-temporal
      characteristics. METHODS: We conducted retrospective analysis of line lists
      obtained from 10 of the 18 states that submitted line lists to the Federal
      Ministry of Health (FMOH). We described the outbreak by time, place and person
      and calculated the attack rates by state as well as the age- and sex-specific CFR
      from cholera cases for whom information on age, sex, place of residence, onset of
      symptoms and outcome were available. RESULTS: A total of 21,111 cases were
      reported with an overall attack rate and CFR of 47.8 cases /100,000 population
      and 5.1%, respectively. The CFR ranged in the states between 3.8% and 8.9%. The
      age-specific CFR was highest among individuals 65 years and above (14.6%). The
      epidemiological curve showed three peaks with increasing number of weekly
      reported cases. A geographical clustering of LGAs reporting cholera cases could
      be seen in all ten states. During the third peak which coincided with flooding in
      five states the majority of newly affected LGAs were situated next to LGAs with
      previously reported cholera cases, only few isolated outbreaks were seen.
      CONCLUSION: Our study showed a cholera outbreak that grew in magnitude and spread
      to involve the whole northern part of the country. It also highlights challenges
      of suboptimal surveillance and response in developing countries as well as
      potential endemicity of cholera in the northern part of Nigeria. There is the
      need for a harmonized, coordinated approach to cholera outbreaks through
      effective surveillance and response with emphasis on training and motivating
      front line health workers towards timely detection, reporting and response.
      Findings from the report should be interpreted with caution due to the high
      number of cases with incomplete information, and lack of data from eight states.

PMID- 25399403
TI  - Scaling laws in emotion-associated words and corresponding network topology.
AB  - We investigated whether scaling laws were present in the appearance-frequency
      distribution of emotion-associated words and determined whether the network
      constructed from those words had small-world or scale-free properties. Over 1,400
      participants were asked to write down the first single noun that came to mind in
      response to nine emotional cue words, resulting in a total of 12,556 responses.
      We identified Zipf's law in the distribution of the data, as the slopes of the
      regression lines reached approximately -1.0 in the appearance frequencies for
      each emotional cue word. This suggested that the emotion-associated words had a
      clear regularity, were not randomly generated, were scale-invariant, and were
      influenced by unification/diversification forces. Thus, we predicted that the
      emotional intensity of the words might play an important role for a Zipf's law.
      Moreover, we also found that the 1-mode network of emotion-associated words
      clearly had small-world properties in terms of the network topologies of
      clustering, average distance, and small-worldness value, indicating that all
      nodes (words) were highly interconnected with each other and were only a few
      short steps apart. Furthermore, the data suggested the possibility of a scale
      free property. Interestingly, we were able to identify hub words with neutral
      emotional content, such as 'dog', 'woman', and 'face', indicating that these
      neutral words might be an intermediary between words with conflicting emotional
      valence. Additionally, efficiency and optimal navigation in terms of complex
      networks were discussed. 

PMID- 25399404
TI  - Autonomic dysfunction: a driving force for myocardial fibrosis in young Duchenne
      muscular dystrophy patients?
AB  - Cardiac manifestations of Duchenne muscular dystrophy (DMD) include progressive
      cardiac dysfunction and an elevated resting heart rate (HR). We hypothesized this
      elevated HR reflects autonomic dysfunction that can be identified by heart rate
      variability (HRV) analyses which will be associated with myocardial fibrosis by
      cardiac magnetic resonance imaging (cMR). DMD patients (N = 74) and controls (N =
      17) had time and frequency domain HRV analyses calculated via Holter monitoring.
      Cardiac magnetic resonance imaging was performed on DMD cases only. chi (2) test,
      T test, ANOVA, and logistic regression were used to perform comparisons between
      groups. A p value of <0.05 was used for statistical significance. DMD cases had
      higher resting average HR than controls (99.4 +/- 8.9, 85.4 + 6.2, p < 0.001).
      Among HRV variables, decreases were seen in the following: standard deviation of
      R to R intervals, the percent RR intervals differing by >50 ms from previous RR
      interval, the root-meansquare of successive differences of RR intervals, the
      standard deviation of the mean R to R segment (SDANN), low frequency, and high
      frequency domain, all p values 0.001. Maximum HR and SDANN most significantly
      associated with positive LGE on cMR (p = 0.008, p = 0.016). DMD cases on beta
      blocker had an average HR lower than those not on beta blocker (p = 0.009), but
      with no difference in HRV analysis. DMD patients have reduced HRV and therefore
      autonomic dysfunction prior to the onset of heart failure which is associated
      with myocardial fibrosis. 

PMID- 25399405
TI  - rs11671784 G/A and rs895819 A/G polymorphisms inversely affect gastric cancer
      susceptibility and miR-27a expression in a Chinese population.
AB  - BACKGROUND: rs895819 and rs11671784 are 2 SNPs in miR-27a that can influence the
      expression of mature miRNA. However, their role in gastric cancer development is
      still not well understood. This study aimed to determine whether these 2
      polymorphisms are associated with gastric cancer risk in a Chinese population and
      how they influence the expression of miR-27a. MATERIAL/METHODS: This was a case
      control study and recruited 278 gastric cases and 278 healthy matched controls.
      Genotyping of these 2 SNPs among the participants were performed to assess their
      association with gastric cancer risk. Tumor samples from 59 patients who had
      physical resection were used for qRT-PCR analysis of miR-27a expression. To
      further valid the effects of these 2 SNPs, findings of previous studies were
      pooled to generate integrated evidence. RESULTS: Individuals with rs895819 G
      variants exhibited significantly increased risk of gastric cancer, while subjects
      with rs11671784 A variants had significantly reduced gastric cancer risk. Among
      the patients, rs895819 G variants were moderately associated with lymphatic
      invasion and lymph node metastasis, while rs11671784 A variants were associated
      with significantly reduced risk of lymphatic invasion. qRT-PCR results
      demonstrated rs895819 polymorphism contributed to an aberrant process from pri
      miR-27a to pre-miR-27a, but rs11671784 did not affect the transcription and post
      transcription processes of the miR-27a gene. The subsequent meta-analysis largely
      confirmed the effects of these 2 SNPs on gastric cancer risk. CONCLUSIONS:
      rs895819 and rs11671784 inversely affect gastric cancer risk and the influence
      was closely related to their effects on miR-27a expression.

PMID- 25399406
TI  - Toxicogenomics directory of chemically exposed human hepatocytes.
AB  - A long-term goal of numerous research projects is to identify biomarkers for in
      vitro systems predicting toxicity in vivo. Often, transcriptomics data are used
      to identify candidates for further evaluation. However, a systematic directory
      summarizing key features of chemically influenced genes in human hepatocytes is
      not yet available. To bridge this gap, we used the Open TG-GATES database with
      Affymetrix files of cultivated human hepatocytes incubated with chemicals,
      further sets of gene array data with hepatocytes from human donors generated in
      this study, and publicly available genome-wide datasets of human liver tissue
      from patients with non-alcoholic steatohepatitis (NASH), cirrhosis, and
      hepatocellular cancer (HCC). After a curation procedure, expression data of 143
      chemicals were included into a comprehensive biostatistical analysis. The results
      are summarized in the publicly available toxicotranscriptomics directory (
      http://wiki.toxbank.net/toxicogenomics-map/ ) which provides information for all
      genes whether they are up- or downregulated by chemicals and, if yes, by which
      compounds. The directory also informs about the following key features of
      chemically influenced genes: (1) Stereotypical stress response. When chemicals
      induce strong expression alterations, this usually includes a complex but highly
      reproducible pattern named 'stereotypical response.' On the other hand, more
      specific expression responses exist that are induced only by individual compounds
      or small numbers of compounds. The directory differentiates if the gene is part
      of the stereotypical stress response or if it represents a more specific
      reaction. (2) Liver disease-associated genes. Approximately 20 % of the genes
      influenced by chemicals are up- or downregulated, also in liver disease. Liver
      disease genes deregulated in cirrhosis, HCC, and NASH that overlap with genes of
      the aforementioned stereotypical chemical stress response include CYP3A7,
      normally expressed in fetal liver; the phase II metabolizing enzyme SULT1C2;
      ALDH8A1, known to generate the ligand of RXR, one of the master regulators of
      gene expression in the liver; and several genes involved in normal liver
      functions: CPS1, PCK1, SLC2A2, CYP8B1, CYP4A11, ABCA8, and ADH4. (3) Unstable
      baseline genes. The process of isolating and the cultivation of hepatocytes was
      sufficient to induce some stress leading to alterations in the expression of
      genes, the so-called unstable baseline genes. (4) Biological function. Although
      more than 2,000 genes are transcriptionally influenced by chemicals, they can be
      assigned to a relatively small group of biological functions, including energy
      and lipid metabolism, inflammation and immune response, protein modification,
      endogenous and xenobiotic metabolism, cytoskeletal organization, stress response,
      and DNA repair. In conclusion, the introduced toxicotranscriptomics directory
      offers a basis for a rationale choice of candidate genes for biomarker evaluation
      studies and represents an easy to use source of background information on
      chemically influenced genes. 

PMID- 25399408
TI  - Virtual reality using games for improving physical functioning in older adults: a
      systematic review.
AB  - The use of virtual reality through exergames or active video game, i.e. a new
      form of interactive gaming, as a complementary tool in rehabilitation has been a
      frequent focus in research and clinical practice in the last few years. However,
      evidence of their effectiveness is scarce in the older population. This review
      aim to provide a summary of the effects of exergames in improving physical
      functioning in older adults. A search for randomized controlled trials was
      performed in the databases EMBASE, MEDLINE, PsyInfo, Cochrane data base, PEDro
      and ISI Web of Knowledge. Results from the included studies were analyzed through
      a critical review and methodological quality by the PEDro scale. Thirteen studies
      were included in the review. The most common apparatus for exergames intervention
      was the Nintendo Wii gaming console (8 studies), followed by computers games,
      Dance video game with pad (two studies each) and only one study with the Balance
      Rehabilitation Unit. The Timed Up and Go was the most frequently used instrument
      to assess physical functioning (7 studies). According to the PEDro scale, most of
      the studies presented methodological problems, with a high proportion of scores
      below 5 points (8 studies). The exergames protocols and their duration varied
      widely, and the benefits for physical function in older people remain
      inconclusive. However, a consensus between studies is the positive motivational
      aspect that the use of exergames provides. Further studies are needed in order to
      achieve better methodological quality, external validity and provide stronger
      scientific evidence. 

PMID- 25399407
TI  - Chemerin as a novel non-invasive serum marker of intrahepatic lipid content in
      obese children.
AB  - BACKGROUND: Ectopic hepatic lipid accumulation is closely related to the
      development of insulin resistance, which is regarded as one of the most
      significant risk factors of non-alcoholic fatty liver disease (NAFLD). The
      current study has shown that fat tissue constitutes an important endocrine organ
      with its own production and metabolism of many biologically active substances,
      among which adipokines play an important role. Classic adipokines (e.g. leptin,
      adiponectin, resistin) are fat-derived hormones which serum level is altered in
      patients with NAFLD. The role of novel adipokines in the pathomechanism of this
      disease is not clear. Therefore, the aim of our study was to evaluate the serum
      concentrations of chemerin, omentin and vaspin in obese children with NAFLD.
      METHODS: Forty-five obese children, aged 7-17 years old, were admitted to our
      Department with suspected liver disease (hepatomegaly, and/or ultrasonographic
      liver brightness, and/or increased ALT activity). Viral hepatitides, as well as
      autoimmune and metabolic liver diseases were excluded. Fasting serum levels of
      chemerin, omentin and vaspin were determined. The grade of liver steatosis in
      ultrasound was graded according to Saverymuttu. (1)HMR spectroscopy was performed
      with a 1.5 T scanner and with PRESS sequencing. RESULTS: Fatty liver was
      confirmed in 39 children by ultrasound and in 33 patients by (1)HMRS (19 of them
      also had increased ALT activity /NAFLD/). Chemerin and vaspin levels were
      significantly higher in children with NAFLD compared to the control group (n =
      30). The concentration of chemerin was significantly higher in children with
      advanced liver steatosis compared to non-hepatopathic patients (p = 0,02).
      Significant positive correlations were found between the total liver lipids in
      (1)HMRS and chemerin (r = 0,33; p = 0,02) and vaspin (r = 0,4; p = 0,006). The
      ability of serum chemerin (cut-off = 190 ng/ml, Se = 75%, Sp = 58%) to
      differentiate children with fatty liver in (1)HMRS from those without steatosis
      was significant (AUC = 0,7, p = 0,04). Omentin and vaspin did not allow a useful
      prediction to be made. CONCLUSION: Chemerin seems to be the most suitable non
      invasive biomarker in predicting both intrahepatic lipid content in obese
      children and advanced liver steatosis in children with NAFLD.

PMID- 25399409
TI  - High-resolution melting analysis reveals low Plasmodium parasitaemia infections
      among microscopically negative febrile patients in western Kenya.
AB  - BACKGROUND: Microscopy and rapid diagnostic tests (RDTs) are common tools for
      diagnosing malaria, but are deficient in detecting low Plasmodium parasitaemia. A
      novel molecular diagnostic tool (nPCR-HRM) that combines the sensitivity and
      specificity of nested PCR (nPCR) and direct PCR-high resolution melting analysis
      (dPCR-HRM) was developed. To evaluate patterns of anti-malarial drug
      administration when no parasites are detected, nPCR-HRM was employed to screen
      blood samples for low parasitaemia from febrile patients without microscopically
      detectable Plasmodium infections in a rural malaria-endemic setting. METHODS:
      Blood samples (n = 197) were collected in two islands of Lake Victoria, Kenya,
      from febrile patients without Plasmodium detectable by microscopy or RDTs. 18S
      rRNA gene sequences were amplified from extracted DNA by nPCR-HRM, nPCR, and dPCR
      HRM to detect and differentiate Plasmodium parasites. The limits of detection
      (LoD) were compared using serial dilutions of the WHO International Standard for
      P. falciparum DNA. Data on administration of anti-malarials were collected to
      estimate prescription of anti-malarial drugs to patients with and without low
      parasitaemia Plasmodium infections. RESULTS: The coupled nPCR-HRM assay detected
      Plasmodium parasites with greater sensitivity (LoD = 236 parasites/mL) than
      either nPCR (LoD = 4,700 parasites/mL) or dPCR-HRM (LoD = 1,490 parasites/mL).
      Moreover, nPCR-HRM detected and differentiated low-parasitaemia infections in
      significantly greater proportions of patients than did either nPCR or dPCR-HRM (p
      value <0.001). Among these low-parasitaemia infections, 67.7% of patients were
      treated with anti-malarials, whereas 81.5% of patients not infected with
      Plasmodium parasites were treated with anti-malarials. CONCLUSIONS: The enhanced
      sensitivity of nPCR-HRM demonstrates limitations of differential febrile illness
      diagnostics in rural malaria endemic settings that confound epidemiological
      estimates of malaria, and lead to inadvertent misadministration of anti-malarial
      drugs. This is the first study that employs low-parasitaemia Plasmodium
      diagnostics to quantify the prescription of anti-malarial drugs to both non
      malaria febrile patients and patients with low-parasitaemia Plasmodium
      infections. nPCR-HRM enhances low-parasitaemia malaria diagnosis and can
      potentially surmount the deficiencies of microscopy and RDT-based results in
      determining low-parasitaemia Plasmodium infection rates for evaluating malaria
      elimination efforts. The findings highlight the need for improved differential
      diagnostics of febrile illness in remote malaria endemic regions.

PMID- 25399410
TI  - Early and mid-term results of isolated aortic valve replacement for aortic
      stenosis in octogenarians.
AB  - OBJECTIVE: As transcatheter aortic valve implantation (TAVI) may become a
      potential treatment for high-risk patients with aortic stenosis (AS), evaluation
      of outcomes after open aortic valve replacement (AVR) in elderly patients is
      warranted. We documented early and late outcomes after isolated AVR in
      octogenarians compared with younger age groups. METHODS: From January 2007 to
      December 2012, 136 patients underwent isolated AVR for AS (mean age 71.3 years,
      39% males) and were classified into two groups (octogenarians and non
      octogenarians). Twenty-four percent were aged 80 years or older. Forty-six
      percent of all patients were in New York Heart Association functional class III
      IV. The estimated Society of Thoracic Surgeons and Japan operative mortalities
      were 3.4 and 2.5%, respectively. RESULT: The 30-day mortality was 0%. One in
      hospital death occurred from low output syndrome and congestive heart failure in
      the non-octogenarian group. Postoperative morbidity was not statistically
      significant different between the age groups. All of the patients-with the
      exception of one case of in-hospital death and one patient who was transferred to
      another hospital-were discharged (postoperative length of stay, 16.4 days). The
      actuarial survival for 3 years by age group was 89.8% in octogenarians compared
      with 93.2% in non-octogenarians. CONCLUSION: Recent results show that isolated
      AVR for severe AS can be performed with a low operative mortality and morbidity
      regardless of age. TAVI may be an alternative for high-risk patients, but
      isolated AVR remains the standard intervention for AS even in increased age.

PMID- 25399412
TI  - Do increasing rates of loss to follow-up in antiretroviral treatment programs
      imply deteriorating patient retention?
AB  - In several studies of antiretroviral treatment (ART) programs for persons with
      human immunodeficiency virus infection, investigators have reported that there
      has been a higher rate of loss to follow-up (LTFU) among patients initiating ART
      in recent years than among patients who initiated ART during earlier time
      periods. This finding is frequently interpreted as reflecting deterioration of
      patient retention in the face of increasing patient loads. However, in this paper
      we demonstrate by simulation that transient gaps in follow-up could lead to bias
      when standard survival analysis techniques are applied. We created a simulated
      cohort of patients with different dates of ART initiation. Rates of ART
      interruption, ART resumption, and mortality were assumed to remain constant over
      time, but when we applied a standard definition of LTFU, the simulated
      probability of being classified LTFU at a particular ART duration was
      substantially higher in recently enrolled cohorts. This suggests that much of the
      apparent trend towards increased LTFU may be attributed to bias caused by
      transient interruptions in care. Alternative statistical techniques need to be
      used when analyzing predictors of LTFU--for example, using "prospective"
      definitions of LTFU in place of "retrospective" definitions. Similar
      considerations may apply when analyzing predictors of LTFU from treatment
      programs for other chronic diseases.

PMID- 25399413
TI  - Counterpoint: moving from potential-outcomes thinking to doing--changing research
      planning to enable successful health outcomes research.
AB  - The potential-outcomes framework is an appealing new approach that imposes a
      degree of formal conceptual modeling beyond traditional epidemiologic methods for
      assessing associations between air pollution and health. However, it introduces a
      number of additional factors to consider when selecting intervention and
      especially control conditions that call for forward-thinking research designs. We
      propose that researchers seeking to implement the potential-outcomes framework
      consider the use of prospective designs that provide more opportunities to
      establish well-defined intervention and control populations and determine causal
      relationships between air quality and health. In implementing these prospective
      research designs, collaboration between researchers and those who implement the
      interventions can improve the understanding of how a planned intervention
      actually occurs, thereby improving the characterization of emissions and air
      quality responses to the intervention. By looking ahead, epidemiologists can take
      advantage of upcoming regulatory interventions to design successful health
      outcomes research programs. 

PMID- 25399414
TI  - Point: clarifying policy evidence with potential-outcomes thinking--beyond
      exposure-response estimation in air pollution epidemiology.
AB  - The regulatory environment surrounding policies to control air pollution warrants
      a new type of epidemiologic evidence. Whereas air pollution epidemiology has
      typically informed policies with estimates of exposure-response relationships
      between pollution and health outcomes, these estimates alone cannot support
      current debates surrounding the actual health effects of air quality regulations.
      We argue that directly evaluating specific control strategies is distinct from
      estimating exposure-response relationships and that increased emphasis on
      estimating effects of well-defined regulatory interventions would enhance the
      evidence that supports policy decisions. Appealing to similar calls for
      accountability assessment of whether regulatory actions impact health outcomes,
      we aim to sharpen the analytic distinctions between studies that directly
      evaluate policies and those that estimate exposure-response relationships, with
      particular focus on perspectives for causal inference. Our goal is not to review
      specific methodologies or studies, nor is it to extoll the advantages of "causal"
      versus "associational" evidence. Rather, we argue that potential-outcomes
      perspectives can elevate current policy debates with more direct evidence of the
      extent to which complex regulatory interventions affect health. Augmenting the
      existing body of exposure-response estimates with rigorous evidence of the causal
      effects of well-defined actions will ensure that the highest-level epidemiologic
      evidence continues to support regulatory policies. 

PMID- 25399415
TI  - GenoBase: comprehensive resource database of Escherichia coli K-12.
AB  - Comprehensive experimental resources, such as ORFeome clone libraries and
      deletion mutant collections, are fundamental tools for elucidation of gene
      function. Data sets by omics analysis using these resources provide key
      information for functional analysis, modeling and simulation both in individual
      and systematic approaches. With the long-term goal of complete understanding of a
      cell, we have over the past decade created a variety of clone and mutant sets for
      functional genomics studies of Escherichia coli K-12. We have made these
      experimental resources freely available to the academic community worldwide.
      Accordingly, these resources have now been used in numerous investigations of a
      multitude of cell processes. Quality control is extremely important for
      evaluating results generated by these resources. Because the annotation has been
      changed since 2005, which we originally used for the construction, we have
      updated these genomic resources accordingly. Here, we describe GenoBase
      (http://ecoli.naist.jp/GB/), which contains key information about comprehensive
      experimental resources of E. coli K-12, their quality control and several omics
      data sets generated using these resources. 

PMID- 25399416
TI  - Landscape of target:guide homology effects on Cas9-mediated cleavage.
AB  - To study target sequence specificity, selectivity, and reaction kinetics of
      Streptococcus pyogenes Cas9 activity, we challenged libraries of random variant
      targets with purified Cas9::guide RNA complexes in vitro. Cleavage kinetics were
      nonlinear, with a burst of initial activity followed by slower sustained
      cleavage. Consistent with other recent analyses of Cas9 sequence specificity, we
      observe considerable (albeit incomplete) impairment of cleavage for targets
      mutated in the PAM sequence or in 'seed' sequences matching the proximal 8 bp of
      the guide. A second target region requiring close homology was located at the
      other end of the guide::target duplex (positions 13-18 relative to the PAM).
      Sequences flanking the guide+PAM region had measurable (albeit modest) effects on
      cleavage. In addition, the first-base Guanine constraint commonly imposed by gRNA
      expression systems has little effect on overall cleavage efficiency. Taken
      together, these studies provide an in vitro understanding of the complexities of
      Cas9-gRNA interaction and cleavage beyond the general paradigm of site
      determination based on the 'seed' sequence and PAM. 

PMID- 25399417
TI  - LncRNAWiki: harnessing community knowledge in collaborative curation of human
      long non-coding RNAs.
AB  - Long non-coding RNAs (lncRNAs) perform a diversity of functions in numerous
      important biological processes and are implicated in many human diseases. In this
      report we present lncRNAWiki (http://lncrna.big.ac.cn), a wiki-based platform
      that is open-content and publicly editable and aimed at community-based curation
      and collection of information on human lncRNAs. Current related databases are
      dependent primarily on curation by experts, making it laborious to annotate the
      exponentially accumulated information on lncRNAs, which inevitably requires
      collective efforts in community-based curation of lncRNAs. Unlike existing
      databases, lncRNAWiki features comprehensive integration of information on human
      lncRNAs obtained from multiple different resources and allows not only existing
      lncRNAs to be edited, updated and curated by different users but also the
      addition of newly identified lncRNAs by any user. It harnesses community
      collective knowledge in collecting, editing and annotating human lncRNAs and
      rewards community-curated efforts by providing explicit authorship based on
      quantified contributions. LncRNAWiki relies on the underling knowledge of
      scientific community for collective and collaborative curation of human lncRNAs
      and thus has the potential to serve as an up-to-date and comprehensive
      knowledgebase for human lncRNAs. 

PMID- 25399418
TI  - The OMA orthology database in 2015: function predictions, better plant support,
      synteny view and other improvements.
AB  - The Orthologous Matrix (OMA) project is a method and associated database
      inferring evolutionary relationships amongst currently 1706 complete proteomes
      (i.e. the protein sequence associated for every protein-coding gene in all
      genomes). In this update article, we present six major new developments in OMA:
      (i) a new web interface; (ii) Gene Ontology function predictions as part of the
      OMA pipeline; (iii) better support for plant genomes and in particular homeologs
      in the wheat genome; (iv) a new synteny viewer providing the genomic context of
      orthologs; (v) statically computed hierarchical orthologous groups subsets
      downloadable in OrthoXML format; and (vi) possibility to export parts of the all
      against-all computations and to combine them with custom data for 'client-side'
      orthology prediction. OMA can be accessed through the OMA Browser and various
      programmatic interfaces at http://omabrowser.org. 

PMID- 25399421
TI  - New insights into the QuikChangeTM process guide the use of Phusion DNA
      polymerase for site-directed mutagenesis.
AB  - The QuikChangeTM site-directed mutagenesis method is popular but imperfect. An
      improvement by using partially overlapping primers has been reported several
      times; however, it is incompatible with the proposed mechanism. The QuikChangeTM
      method using complementary primers is proposed to linearly amplify a target
      plasmid with the products annealing to produce double-stranded DNA molecules with
      5'-overhangs. The overhang annealing is supposed to form circular plasmids with
      staggered breaks, which can be repaired in Escherichia coli after transformation.
      Here, we demonstrated that the PCR enzyme fills the 5'-overhangs in the early
      cycles, and the product is then used as the template for exponential
      amplification. The linear DNA molecules with homologous ends are joined to
      generate the plasmid with the desired mutations through homologous recombination
      in E. coli. The correct understanding is important to method improvements,
      guiding us to use partially overlapping primers and Phusion DNA polymerase for
      site-directed mutagenesis. Phusion did not amplify a plasmid with complementary
      primers but used partially overlapping primers to amplify the plasmid, producing
      linear DNA molecules with homologous ends for site-directed mutagenesis.

PMID- 25399420
TI  - The H19/let-7 double-negative feedback loop contributes to glucose metabolism in
      muscle cells.
AB  - The H19 lncRNA has been implicated in development and growth control and is
      associated with human genetic disorders and cancer. Acting as a molecular sponge,
      H19 inhibits microRNA (miRNA) let-7. Here we report that H19 is significantly
      decreased in muscle of human subjects with type-2 diabetes and insulin resistant
      rodents. This decrease leads to increased bioavailability of let-7, causing
      diminished expression of let-7 targets, which is recapitulated in vitro where H19
      depletion results in impaired insulin signaling and decreased glucose uptake.
      Furthermore, acute hyperinsulinemia downregulates H19, a phenomenon that occurs
      through PI3K/AKT-dependent phosphorylation of the miRNA processing factor KSRP,
      which promotes biogenesis of let-7 and its mediated H19 destabilization. Our
      results reveal a previously undescribed double-negative feedback loop between
      sponge lncRNA and target miRNA that contributes to glucose regulation in muscle
      cells. 

PMID- 25399422
TI  - LncRNA2Target: a database for differentially expressed genes after lncRNA
      knockdown or overexpression.
AB  - Long non-coding RNAs (lncRNAs) have emerged as critical regulators of genes at
      epigenetic, transcriptional and post-transcriptional levels, yet what genes are
      regulated by a specific lncRNA remains to be characterized. To assess the effects
      of the lncRNA on gene expression, an increasing number of researchers profiled
      the genome-wide or individual gene expression level change after knocking down or
      overexpressing the lncRNA. Herein, we describe a curated database named
      LncRNA2Target, which stores lncRNA-to-target genes and is publicly accessible at
      http://www.lncrna2target.org. A gene was considered as a target of a lncRNA if it
      is differentially expressed after the lncRNA knockdown or overexpression.
      LncRNA2Target provides a web interface through which its users can search for the
      targets of a particular lncRNA or for the lncRNAs that target a particular gene.
      Both search types are performed either by browsing a provided catalog of lncRNA
      names or by inserting lncRNA/target gene IDs/names in a search box. 

PMID- 25399423
TI  - dbSNO 2.0: a resource for exploring structural environment, functional and
      disease association and regulatory network of protein S-nitrosylation.
AB  - Given the increasing number of proteins reported to be regulated by S
      nitrosylation (SNO), it is considered to act, in a manner analogous to
      phosphorylation, as a pleiotropic regulator that elicits dual effects to regulate
      diverse pathophysiological processes by altering protein function, stability, and
      conformation change in various cancers and human disorders. Due to its importance
      in regulating protein functions and cell signaling, dbSNO
      (http://dbSNO.mbc.nctu.edu.tw) is extended as a resource for exploring structural
      environment of SNO substrate sites and regulatory networks of S-nitrosylated
      proteins. An increasing interest in the structural environment of PTM substrate
      sites motivated us to map all manually curated SNO peptides (4165 SNO sites
      within 2277 proteins) to PDB protein entries by sequence identity, which provides
      the information of spatial amino acid composition, solvent-accessible surface
      area, spatially neighboring amino acids, and side chain orientation for 298
      substrate cysteine residues. Additionally, the annotations of protein molecular
      functions, biological processes, functional domains and human diseases are
      integrated to explore the functional and disease associations for S
      nitrosoproteome. In this update, users are allowed to search a group of
      interested proteins/genes and the system reconstructs the SNO regulatory network
      based on the information of metabolic pathways and protein-protein interactions.
      Most importantly, an endogenous yet pathophysiological S-nitrosoproteomic dataset
      from colorectal cancer patients was adopted to demonstrate that dbSNO could
      discover potential SNO proteins involving in the regulation of NO signaling for
      cancer pathways. 

PMID- 25399425
TI  - Elemental distribution in reproductive and neural organs of the Epilachna
      nylanderi (Coleoptera: Coccinellidae), a phytophage of nickel hyperaccumulator
      Berkheya coddii (Asterales: Asteraceae) by micro-PIXE.
AB  - The phenomenon of metal hyperaccumulation by plants is often explained by a
      pathogen or herbivore defense hypothesis. However, some insects feeding on metal
      hyperaccumulating plants are adapted to the high level of metals in plant
      tissues. Former studies on species that feed on the leaves of Berkheya coddii
      Roessler 1958 (Asteraceae), a nickel-hyperaccumulating plant, demonstrated
      several protective mechanisms involved in internal distribution, immobilization,
      and elimination of Ni from the midgut and Malpighian tubules. These species are
      mainly coleopterans, including the lady beetle, Epilachna nylanderi (Mulsant
      1850) (Coleoptera: Coccinellidae), collected from the ultramafic ecosystem near
      Barberton in South Africa. By performing particle-induced X-ray emission
      microanalysis elemental microanalysis (PIXE), this study examined whether Ni may
      be harmful to internal body systems that decide on insect reactivity (central
      nervous system [CNS]), their reproduction, and the relationships between Ni and
      other micronutrients. Data on elemental distribution of nine selected elements in
      target organs of E. nylanderi were compared with the existing data for other
      insect species adapted to the excess of metals. Micro-PIXE maps of seven regions
      of the CNS showed Ni mainly in the neural connectives, while cerebral ganglia
      were better protected. Concentrations of other bivalent metals were lower than
      those of Ni. Testis, compared with other reproductive organs, showed low amounts
      of Ni. Zn was effectively regulated at physiological dietary levels. In insects
      exposed to excess dietary Zn, it was also accumulated in the reproductive organs.
      Comparison of E. nylanderii with other insects that ingest hyperaccumulating
      plants, especially chrysomelid Chrysolina clathrata (Clark) (Coleoptera:
      Chrysomelidae), showed lower protection of the CNS and reproductive organs. 

PMID- 25399426
TI  - Induced senescence promotes the feeding activities and nymph development of Myzus
      persicae (Hemiptera: Aphididae) on potato plants.
AB  - The effect of dark-induced senescence on Solanum tuberosum L. (Solanales:
      Solanaceae) plants was assessed on the feeding behavior and performance of the
      green peach aphid, Myzus persicae Sulzer (Hemiptera: Aphididae). Senescence was
      induced by covering the basal part of the plant with a black cloth for 5 d,
      avoiding the light passage, but keeping the apical buds uncovered. The basal part
      of control plants was covered with a white nonwoven cloth. The degree of
      senescence was determined by measuring the chlorophyll content of the covered
      leaves. The performance and feeding behavior of M. persicae were studied on the
      uncovered nonsenescent apical leaves. The aphid's performance was evaluated by
      measuring nymphal mortality and prereproductive time. Aphid feeding behavior was
      monitored by the electrical penetration graph technique. In plants with dark
      induced senescence, the aphids showed a reduction in their prereproductive time.
      Aphids also spent more time ingesting sap from the phloem than in control plants
      and performed more test probes after the first sustained ingestion of phloem sap.
      These data suggest that M. persicae's phloem activities and nymph development
      benefit from the nutritional enrichment of phloem sap, derived from dark-induced
      senescence on potato plants. The induced senescence improved plant acceptance by
      M. persicae through an increase in sap ingestion that likely resulted in a
      reduction in developmental time.

PMID- 25399427
TI  - Description of Rhagoletis cerasi (Diptera: Tephritidae) pupal developmental
      stages: indications of prolonged diapause.
AB  - The European cherry fruit fly, Rhagoletis cerasi (L.) (Diptera: Tephritidae), is
      the key pest of sweet and sour cherries in many European countries and west Asia.
      It is a univoltine species of the west Palaearctic zone that undergoes obligatory
      pupal diapause. In this study, the development of R. cerasi pupae that were
      brought to an optimum temperature for postdiapause development following a long
      chilling period is described. The six most representative developmental stages
      within the puparium are illustrated, and the developmental progression among the
      stages after the end of the chilling period is quantified. Within 20 d
      postchilling, there was a gradual progress from stage I to pharate adult.
      However, ~30% of the pupae remained at the transitional stage II, after 20 d at
      25 degrees C (optimum temperature for development). This suggests that a
      proportion of pupae remain at an intermediate developmental stage for an extended
      period of time that goes beyond 20 d postchilling. The pupal stage II might be
      related to diapause termination and responsiveness to environmental cues. It may
      also define the time before developmental progress to pharate adult. This finding
      agrees with previous studies proposing that a number of R. cerasi pupae undergo
      prolonged diapause, though the morphological characteristics of these pupae have
      never been described before. 

PMID- 25399428
TI  - Two new species of the new world genus Rhinoleucophenga (Diptera: drosophilidae).
AB  - The genus Rhinoleucophenga Hendel (1917) encompasses 21 described species but is
      still not well known as a taxon. Even the currently described species lack full
      descriptions, i.e., illustrations of the male genitalia are absent, which makes
      their identification difficult. This study describes two new species of
      Rhinoleucophenga with the illustration of their male genitalia. 

PMID- 25399429
TI  - Sterilization of Chrysomya putoria (Insecta: Diptera: Calliphoridae) eggs for use
      in biotherapy.
AB  - Large-scale, quality-controlled laboratory production of fly larvae is needed for
      biotherapy. The objective of this study was to assess the action of
      glutaraldehyde on the sterilization of Chrysomya putoria eggs by applying
      pharmaceutical sterility tests. Egg masses with 0.600 g were divided into three
      parts of 0.200 g, the eggs were separated using sterile distilled water, and the
      suspensions obtained were mixed with activated 2% glutaraldehyde solution. After
      15-min contact, the suspensions were filtered through Whatman filter paper, and
      the glutaraldehyde residue obtained in the filtrate was neutralized by rinsing
      with Tryptone Soy Broth. The treated eggs were placed aseptically on Petri dishes
      containing gauze moistened with sterile saline solution. About 10% of the
      sterilized mass was transferred to test tubes containing Tryptone Soy Broth and
      Fluid Thioglycollate Broth. The tubes were incubated, respectively, at 22.5 and
      35.0 degrees C for 14 d to verify egg mass sterility. The plates containing the
      rest of the eggs (90%) were sealed with plastic film and kept in a climatized
      chamber at 30 degrees C/d, 28 degrees C per night, 60 +/- 10% relative humidity,
      and under a 12-h light period to assess insect viability and survival. Each
      experiment was carried out in triplicate using a biological class II safety
      cabinet. No change in color or turgidity was observed with the agent tested,
      proving the sterility of the product and that there was no trace of
      contamination. Forty larvae (in three replications) in the periods of 12, 24, and
      48 h after sterilization, when transferred to diet, produced larvae, pupae, and
      total viability similar to the control (larvae without sterilization). However,
      for the 72-h treatment, larvae and total viability were significantly lower than
      for the other treatments. There was no significant difference for the pupal
      stage. The product tested was shown to be efficacious for use as a sterilizer of
      C. putoria eggs for all the parameters assessed.

PMID- 25399430
TI  - Molecular cloning and xenobiotic induction of seven novel cytochrome P450
      monooxygenases in Aedes albopictus.
AB  - Cytochrome P450 monooxygenase (P450) is a superfamily of enzymes that is
      important in metabolism of endogenous and exogenous compounds. In insects, these
      enzymes confer resistance to insecticides through its metabolic activities.
      Members of P450 from family 6 in insects are known to play a role in such
      function. In this study, we have isolated seven novel family 6 P450 from Aedes
      albopictus (Skuse) (Diptera: Culicidae), a vector of dengue and chikungunya
      fever. Induction profile of these seven genes was studied using several
      insecticides and xenobiotics. It was found that deltamethrin and permethrin did
      not induce expression of any genes. Another insecticide, temephos, inhibited
      expression of CYP6P15 for fivefold and twofold for CYP6N29, CYP6Y7, and CYP6Z18.
      In addition, copper II sulfate induced expression of CYP6M17 and CYP6N28 for up
      to sixfold. Benzothiazole (BZT), a tire leachate induced the expression of
      CYP6M17 by fourfold, CYP6N28 by sevenfold, but inhibited the expression of
      CYP6P15 for threefold and CYP6Y7 for twofold. Meanwhile, piperonyl butoxide (PBO)
      induced the expression CYP6N28 (twofold), while it inhibited the expression of
      CYP6P15 (fivefold) and CYP6Y7 (twofold). Remarkably, all seven genes were induced
      two- to eightfold by acetone in larval stage, but not adult stage. Expression of
      CYP6N28 was twofold higher, while expression of CYP6P15 was 15-fold lower in
      adult than larva. The other five P450s were not differentially expressed between
      the larvae and adult. This finding showed that acetone can be a good inducer of
      P450 in Ae. albopictus. On the other hand, temephos can act as good suppressor of
      P450, which may affect its own bioefficacy because it needs to be bioactivated by
      P450. To the best of our knowledge, this is the first report on acetone-inducible
      P450 in insects. Further study is needed to characterize the mechanisms involved
      in acetone induction in P450. 

PMID- 25399431
TI  - Morphometric differentiation in Cornops aquaticum (Orthoptera: Acrididae):
      associations with sex, chromosome, and geographic conditions.
AB  - The water-hyacinth grasshopper Cornops aquaticum (Bruner) (Orthoptera: Acrididae)
      is native to South America and inhabits lowlands from southern Mexico to central
      Argentina and Uruguay. This grasshopper feeds and lays eggs on species from the
      genera Eichhornia and Pontederia. Particularly, Eichhornia crassipes is
      considered "the world's worst water weed," and the release of C. aquaticum was
      proposed as a form of biological control. Morphometric variation on the
      chromosomally differentiated populations from the middle and lower Parana River
      and its possible association with geographic, sex, and chromosomal conditions was
      analyzed. Significant phenotype variation in C. aquaticum population was
      detected. C. aquaticum presents body-size sexual dimorphism, females being bigger
      than males. Female-biased sexual size dimorphism for all five analyzed traits was
      detected. The assessment of variation in sexual size dimorphism for tegmen length
      showed that this trait scaled allometrically, indicating that males and females
      did not vary in a similar fashion. The detected allometry was consistent with
      Rensch's rule demonstrating greater evolutionary divergence in male size than in
      female size and suggests that males are more sensitive to environmental
      condition. The analysis of morphometric variation in the context of chromosome
      constitution showed that the presence of fusion 1/6 was related to body-size
      variation. Fusion carriers displayed bigger body size than standard homozygotes.
      Besides, a positive relationship between tegmen length and the number of fused
      chromosomes was detected, showing a chromosome dose effect. Because the highest
      frequency of fusions has been found in the lower Parana River, a marginal
      environment for this species, the results found would support the hypothesis that
      some supergenes located in the fusions may be favored in the southern
      populations, thus contributing to the establishment and maintenance of the
      polymorphism. 

PMID- 25399432
TI  - Interference of field evidence, morphology, and DNA analyses of three related
      Lysiphlebus aphid parasitoids (Hymenoptera: Braconidae: Aphidiinae).
AB  - This study provides evidence on integrating the morphological, field, and
      laboratory data, and application of the cytochrome oxidase subunit I (COI)
      barcoding gene to the three asexual or sexual Lysiphlebus spp., i.e., Lysiphlebus
      cardui (Marshall), Lysiphlebus confusus Tremblay and Eady and Lysiphlebus fabarum
      (Marshall) (Hymenoptera: Braconidae: Aphidiinae). New aphid- invasive plant
      association, Aphis fabae Scopoli (Hemipreta: Aphididae) on Impatiens glandulifera
      Royle, has been used in the same model area in the Czech Republic under the same
      sampling and rearing method for several consecutive years and throughout the
      season. For molecular identification of these three species, we used DNA
      sequences of the barcoding region of the mitochondrial COI gene. Although our
      results confirmed ecological and morphological differences among L. cardui, L.
      confusus, and L. fabarum, genetic analysis on the basis of COI mitochondrial
      barcoding gene does not support species status of the mentioned Lysiphlebus taxa.
      The level of morphological differentiation in these Lysiphlebus Forster species
      is in accordance with the usual species variability within subfamily Aphidiinae.
      However, it should be examined how appearance of asexual lineages affects the
      morphological or genetical variability. 

PMID- 25399433
TI  - Molecular identification of two prophenoloxidase-activating proteases from the
      hemocytes of Plutella xylostella (Lepidoptera: Plutellidae) and their transcript
      abundance changes in response to microbial challenges.
AB  - The phenoloxidase (PO) activation system plays an important role in insect innate
      immunity, particularly in wound healing and pathogen defense. A key member of
      this system is prophenoloxidase-activating protease (PAP), which is the direct
      activator of prophenoloxidase (proPO). Despite their importance in the insect PO
      activation system, content of studies is limited. In this article, we identify
      two complementary DNAs (cDNAs), PxPAPa and PxPAPb, encoding possible PAPs, from
      immunized larval hemocytes of the diamondback moth, Plutella xylostella (L.), by
      RACE method. PxPAPa is 1,149-bp long and encodes a 382-residue open reading frame
      (ORF) with a predicted 17-residue signal peptide, a clip domain, and a Tryp_Spc
      domain. PxPAPb is 1,650-bp long and encodes a 440-residue ORF with a predicted 20
      residue signal peptide, two clip domains, and a Tryp_Spc domain. PxPAPa and
      PxPAPb have a high sequence similarity to Manduca sexta (L.) PAP1 and PAP3,
      respectively. We also examined the transcript patterns of PxPAPa, PxPAPb, and
      pxPAP3, another clip-domain serine protease gene, response to different microbial
      challenges by using real-time quantitative polymerase chain reaction. The results
      show that the transcript abundance of PxPAPa is significantly increased by
      Micrococcus luteus and Escherichia coli but not Candida albicans. PxPAPb is
      induced only by Mi. luteus, whereas pxPAP3 could be induced by all the microbes
      in the test, but the transcript patterns of Mi. luteus, E. coli, and C. albicans
      are completely different. This study provides new insights into the molecular
      events that occur during the immune response, particularly melanization cascade
      that is involved in encapsulation and nodulation of pathogen or parasite invaders
      via hemocytes in host insects. 

PMID- 25399434
TI  - Early embryonic expression of a putative ecdysteroid-phosphate phosphatase in the
      water flea, Daphnia magna (Cladocera: Daphniidae).
AB  - Ecdysteroids, known as molting hormones, play central roles in the onset of
      molting, metamorphosis, and reproduction in arthropods. The ecdysteroids stored
      in eggs also play an important role in embryogenesis. In insects, ecdysteroids
      are stored as phosphate esters, which are converted to an active form by
      ecdysteroid-phosphate phosphatase (EPPase). Although EPPase is believed to be
      widely conserved in the Ecdysozoa, little is known about its expression in clades
      other than Insecta. In this study, we cloned a putative EPPase gene from a small
      fresh water crustacean known as a water flea, Daphnia magna Straus (Cladocera:
      Daphniidae), and examined its expression during embryogenesis. The amino acid
      sequence of the putative crustacean EPPase cDNA showed high similarity to insect
      EPPase and human suppressor of T-cell receptor signaling-1. We also found that
      the D. magna EPPase was highly expressed during early embryogenesis; its
      expression rapidly decreased 6 h after oviposition. This timing corresponds to
      the onset of organogenesis in D. magna. The expression of EPPase could not be
      detected in diapaused eggs. This is the first report of an EPPase from
      crustaceans, and the results suggest that the function of EPPase is conserved
      between insects and crustaceans.

PMID- 25399435
TI  - Pulmonary artery smooth muscle cell endothelin-1 expression modulates the
      pulmonary vascular response to chronic hypoxia.
AB  - Endothelin-1 (ET-1) increases pulmonary vascular tone through direct effects on
      pulmonary artery smooth muscle cells (PASMC) via membrane-bound ET-1 receptors.
      Circulating ET-1 contributes to vascular remodeling by promoting SMC
      proliferation and migration and inhibiting SMC apoptosis. Although endothelial
      cells (EC) are the primary source of ET-1, whether ET-1 produced by SMC modulates
      pulmonary vascular tone is unknown. Using transgenic mice created by
      crossbreeding SM22alpha-Cre mice with ET-1(flox/flox) mice to selectively delete
      ET-1 in SMC, we tested the hypothesis that PASMC ET-1 gene expression modulates
      the pulmonary vascular response to hypoxia. ET-1 gene deletion and selective
      activity of SM22alpha promoter-driven Cre recombinase were confirmed. Functional
      assays were performed under normoxic (21% O2) or hypoxic (5% O2) conditions using
      murine PASMC obtained from ET-1(+/+) and ET-1(-/-) mic and in human PASMC
      (hPASMC) after silencing of ET-1 using siRNA. Under baseline conditions, there
      was no difference in right ventricular systolic pressure (RVSP) between SM22alpha
      ET-1(-/-) and SM22alpha-ET-1(+/+) (control) littermates. After exposure to
      hypoxia (10% O2, 21-24 days), RVSP was and vascular remodeling were less in
      SM22alpha-ET-1(-/-) mice compared with control littermates (P < 0.01). Loss of ET
      1 decreased PASMC proliferation and migration and increased apoptosis under
      normoxic and hypoxic conditions. Exposure to selective ET-1 receptor antagonists
      had no effect on either the hypoxia-induced hPASMC proliferative or migratory
      response. SMC-specific ET-1 deletion attenuates hypoxia-induced increases in
      pulmonary vascular tone and structural remodeling. The observation that loss of
      ET-1 inhibited SMC proliferation, survival, and migration represents evidence
      that ET-1 derived from SMC plays a previously undescribed role in modulating the
      response of the pulmonary circulation to hypoxia. Thus PASMC ET-1 may modulate
      vascular tone independently of ET-1 produced by EC.

PMID- 25399437
TI  - Multicentre evaluation of perioperative red blood cells transfusions in China.

PMID- 25399436
TI  - Hyperoxia-induced changes in estradiol metabolism in postnatal airway smooth
      muscle.
AB  - Supplemental oxygen, used to treat hypoxia in preterm and term neonates,
      increases the risk of neonatal lung diseases, such as bronchopulmonary dysplasia
      (BPD) and asthma. There is a known sex predilection for BPD, but the underlying
      mechanisms are not clear. We tested the hypothesis that altered, local estradiol
      following hyperoxia contributes to pathophysiological changes observed in
      immature lung. In human fetal airway smooth muscle (fASM) cells exposed to
      normoxia or hyperoxia, we measured the expression of proteins involved in
      estrogen metabolism and cell proliferation responses to estradiol. In fASM cells,
      CYP1a1 expression was increased by hyperoxia, whereas hyperoxia-induced
      enhancement of cell proliferation was blunted by estradiol. Pharmacological
      studies indicated that these effects were attributable to upregulation of CYP1a1
      and subsequent increased metabolism of estradiol to a downstream intermediate 2
      methoxyestradiol. Microarray analysis of mouse lung exposed to 14 days of
      hyperoxia showed the most significant alteration in CYP1a1 expression, with
      minimal changes in expression of five other genes related to estrogen receptors,
      synthesis, and metabolism. Our novel results on estradiol metabolism in fetal and
      early postnatal lung in the context of hyperoxia indicate CYP1a1 as a potential
      mechanism for the protective effect of estradiol in hyperoxia-exposed immature
      lung, which may help explain the sex difference in neonatal lung diseases. 

PMID- 25399438
TI  - Palatal tremor after brachial plexus anaesthesia.

PMID- 25399439
TI  - Caveats of pressure control: lung non-protective ventilation.

PMID- 25399440
TI  - Indications of extracorporeal life support in poly-trauma.

PMID- 25399441
TI  - Unexpected benefit of videolaryngoscopy.

PMID- 25399448
TI  - On the upper threshold phenomenon of extracellular neural stimulation.

PMID- 25399449
TI  - Reply to Rattay.

PMID- 25399450
TI  - Retraction.

PMID- 25399451
TI  - Retraction.

PMID- 25399452
TI  - Preface: musculoskeletal healthcare.

PMID- 25399453
TI  - Guidance for the emergency physician:  post-exposure prophylaxis for children and
      adolescents.

PMID- 25399454
TI  - Addressing the undocumented client.  Legal implications for health care outcomes
      in HIV+ clients.

PMID- 25399455
TI  - Augmented bronchial smooth muscle contractility  induced by aqueous cigarette
      smoke extract in rats.

PMID- 25399456
TI  - Rural pharmacy closures: implications for rural communities.
AB  - Retail pharmacies provide essential services to residents of rural areas and
      serve many communities as the sole provider of pharmacist services. Losing the
      only retail pharmacy within a rural community (census designated city), and
      within a 10 mile radius based on driving distance ("sole community pharmacy"),
      may affect access to prescription and over-the-counter drugs and, in some cases,
      leave the community without proximate access to any clinical provider. This
      policy brief documents the closure of local retail pharmacies in which the
      pharmacist was the only clinical provider available in the community at the time
      the pharmacy closed. Characteristics of the community and the retail pharmacy are
      described. The findings may suggest future policy actions to minimize the risk or
      mitigate the negative consequences of pharmacy closures. Key Findings. (1)
      Between May 1, 2006, and October 31, 2010, 119 sole community pharmacies closed.
      (2) Of those 119 pharmacies, 31 were located in rural communities with no other
      health professionals or clinical providers. (3) In 16 states, at least 1
      community lost a sole community retail pharmacy, and there was no other pharmacy
      within 10 miles (actual driving distance). (4) Of the 31 pharmacy closures in
      communities with no other providers, 17% were located in remote rural areas
      designated with a Rural-Urban Commuting Area (RUCA) score of 10 or higher. Such a
      score means that, on average, 60 minutes of travel time is required to reach an
      urbanized area, and 40 minutes is required to reach a large urban cluster of
      20,000 population or more.

PMID- 25399457
TI  - June 2012: rural MA enrollment and premium update.
AB  - Key Data Findings. (1) Rural Medicare Advantage (MA) enrollment grew to over 1.7
      million in June 2012 (17% of eligible beneficiaries), while total MA enrollment
      grew to nearly 13.4 million (27% of eligible beneficiaries). (2) Rural preferred
      provider organization (PPO) and health maintenance organization (HMO) enrollment
      grew to over 840 thousand (48% of the market) and 532 thousand (31% of the
      market), respectively, while private fee-for-service (PFFS) enrollment fell to
      230 thousand in rural areas (13% of the market). (3) Rural MA enrollment varies
      across the country with concentrations of enrollment on the West Coast, the Great
      Lakes, and the Northeast regions of the United States. (4) The average monthly
      weighted premium for rural MA plans with prescription drugs fell in 2012 to $48
      from $52 in 2011, but it remains significantly higher than the urban average
      which also fell during the same time from $38 to $34. (5) Zero premium plans are
      available to 73% of rural MA beneficiaries and to 95% of urban beneficiaries;
      however, only 48% of rural beneficiaries that have this option choose these plans
      compared to 63% of urban beneficiaries. The resulting average non-zero premium
      was $72 in rural areas in 2012, while the average non-zero premium in urban areas
      was $81. (6) Roughly a third (35%) of rural MA beneficiaries receive their MA
      coverage including prescription drugs without having to pay a premium, however
      this is significantly lower than 60% of urban beneficiaries that do not have to
      pay a premium.

PMID- 25399459
TI  - The uninsured: an analysis by income and geography.
AB  - Key Findings. (1) A larger proportion of the rural population than the urban
      population is uninsured and low income (living at or below 138% of the federal
      poverty line [FPL]) (9.9% as compared to 8.5%) and a larger proportion of the
      rural population than the urban population will be eligible for subsidized Health
      Insurance Marketplace (HIM) coverage due to income levels and current lack of
      insurance (10.7% as compared to 9.6%). (2) Assuming full Medicaid expansion, a
      larger proportion of the rural uninsured than the urban uninsured would be
      eligible for Medicaid (43.5% as compared to 38.5%). (3) A smaller proportion of
      the rural uninsured than the urban uninsured has income above 400% FPL and thus
      will not qualify for either Medicaid or HIM subsidies (10% as compared to 14.1%).
      (4) The proportion of the uninsured population potentially eligible for Medicaid
      expansion is highest in the rural South (47.5%) and lowest in the urban Northeast
      (32.5%) and the rural Northeast (35.8%).

PMID- 25399460
TI  - Accountable care organizations in rural America.
AB  - Key Findings. (1) Medicare Accountable Care Organizations (ACOs) operate in non
      metropolitan counties in every U.S. Census Region. (2) 79 Medicare ACOs operate
      in both metropolitan and non-metropolitan counties. (3) Medicare ACOs operate in
      16.7% of non-metropolitan counties. (4) 9 ACOs operate exclusively in non
      metropolitan counties, including at least 1 in every U.S. Census Region.

PMID- 25399461
TI  - The Frontier Extended Stay Clinic model: a potential health care delivery
      alternative for small rural communities.
AB  - Key Findings. (1) The Frontier Extended Stay Clinic (FESC) demonstration project
      provided expanded emergency services and extended clinic stays to remote rural
      communities. (2) Although the FESC demonstration ended this year, the FESC model
      may be appropriate in rural communities other than the five original
      demonstration sites. (3) FESCs may also be alternatives to very low-volume rural
      hospitals.

PMID- 25399462
TI  - Causes and consequences of rural pharmacy closures: a multi-case study.
AB  - Local rural pharmacies provide essential pharmacy and clinical services to their
      communities. Pharmacists play a critical role in the continuum of care for rural
      residents, and the loss of a local pharmacy may impact access to prescription
      drugs and clinical care. This policy brief identifies factors that contributed to
      the closing of six pharmacies and describes how the affected communities adapted
      to losing locally based services. Key Findings. (1) Five out of the six
      pharmacies studied closed due to retirement and/or difficulties in recruiting a
      successor. (2) In five of the six communities, residents now either drive to the
      nearest pharmacy or use mail-order to receive their prescriptions and, in some
      instances, receive their prescriptions through a courier service from a pharmacy
      in a nearby town. (3) Access to pharmacy services in these communities is of most
      concern for individuals with limited mobility and those who lack a support system
      that can pick up and deliver their prescriptions (e.g., the elderly and people
      with acute conditions).

PMID- 25399463
TI  - Demographic and economic characteristics associated with sole county pharmacy
      closures, 2006-2010.
AB  - Key Findings. Twenty-five counties lost their sole community pharmacy between May
      2006 and December 2010. Among these: (1) The average population density is 10.4
      persons per square mile, compared to 87.4 for the United States. (2) The average
      population decreased by 1.6% between 2000 and 2010. Excluding the largest county,
      the average decrease was 2.4%. (3) The population age 65 years and older
      increased 5.4% between 2000 and 2010. Excluding the largest county, the 65-and
      older population increased 2.1%. (4) The average change in the percentage of
      persons in poverty increased by 0.6 points between 2000 and 2010, from 15.5% to
      16.1%, compared to a 4.0 point increase (11.3% to 15.3%) for the United States.
      (5) The average percentage of people younger than 65 years without health
      insurance was 24.6% in 2010, compared to 16.2% for the United States. (6)
      Nineteen of the 25 counties were designated "whole county" Health Professional
      Shortage Areas (HPSAs), meaning there was a shortage of primary medical care
      physicians across the entire county. (7) The average number of active doctors per
      1,000 persons was 0.44, compared to 2.86 for the United States. Six of the 25
      counties (24%) had no active MDs or DOs in 2010.

PMID- 25399464
TI  - March 2013: Medicare Advantage update.
AB  - Key Data Findings. (1) From March 2012 to March 2013, rural enrollment in
      Medicare Advantage (MA) and other prepaid plans increased by over 200,000
      enrollees, to more than 1.9 million. (2) Preferred provider organization (PPO)
      plan enrollment increased to nearly one million enrollees, accounting for more
      than 51% of the rural MA market (up from 48% in March 2012). (3) Health
      maintenance organization (HMO) enrollment continued to grow in 2013, with over
      31% of the rural MA market, while private fee-for-service (PFFS) plan enrollment
      decreased to less than 10% of market share. (4) Despite recent changes to MA
      payment, rural MA enrollment continues to increase.

PMID- 25399465
TI  - Assessing the impact of rural provider services mix on the Primary Care Incentive
      Payment Program.
AB  - Key Findings. (1) Based on analysis of 2009 Medicare claims data, more than 70%
      of rural primary care physicians (PCP) and non-physician practitioners (NPP)
      qualify for payments under the Primary Care Incentive Payment Program (PCIP)
      threshold (i.e., meet the > 60% of allowable Medicare charges). (2) The average
      incentive payment for qualifying rural PCPs would result in an additional $8,000
      in Medicare patient revenue per year. For qualifying NPPs, the result is an
      additional $3,000 in Medicare patient revenue per year. (3) Only 9% of non
      qualifying rural primary care providers were within 10 percentage points of the
      minimum threshold (60%) of Medicare allowed charges to qualify for PCIP payments.

PMID- 25399466
TI  - 2012 rural Medicare Advantage quality ratings and bonus payments.
AB  - Key Data Findings. (1) The average rural Medicare Advantage (MA) plan enrollee in
      2012 experienced a quality rating of 3.60 stars (of a potential 5.0), compared
      with a rating of 3.71 stars experienced by urban enrollees. (2) The measured
      rural-urban difference in the MA plan quality is a result of the difference in
      the composition of the enrollment and plan availability in MA markets, rather
      than differences between MA plans of the same type. (a) In general, rural
      Medicare beneficiaries often have limited MA plans available from which to
      choose, and typically have lower quality ratings than urban MA plans. (b) Rural
      MA beneficiaries are more likely to be enrolled in preferred provider
      organization (PPO) plans than in health maintenance organization (HMO) plans. (c)
      PPO plans have lower quality ratings on average than HMO plans. (d) HMO plans had
      the highest average quality rating at 3.83 and 3.78 stars, respectively, in rural
      and urban areas. PPO plans had lower quality ratings, at 3.52 and 3.50,
      respectively. (3) In rural areas, 32% of the MA population is enrolled in a plan
      with a star rating of 4.0 or higher, and 92% are enrolled in a plan with a star
      rating of at least 3.0, as contrasted to urban enrollment of 36% and 94%
      respectively, making these plans eligible for quality based bonus payments. (4)
      The quality rating of rural MA plans varies significantly across the country,
      with the highest quality ratings in rural areas in Minnesota, Iowa, Wisconsin,
      Oregon, Pennsylvania, and Maine.

PMID- 25399467
TI  - The uninsured: an analysis by age, income, and geography.
AB  - Key Findings. (1) Assuming Medicaid expansion in each of the fifty states and the
      District of Columbia, a larger proportion of the rural (non-metropolitan)
      uninsured (43.5%) than the urban uninsured (38.5%) would be eligible for
      Medicaid. (2) In both urban and rural places, across the adult non-elderly
      population, uninsured rates decline dramatically with age. (3) Within each age
      group of the uninsured, rural people are less likely to have incomes above 400%
      of the federal poverty level (FPL), meaning that overall more rural uninsured
      would be eligible for some form of health insurance assistance under the Patient
      Protection and Affordable Care Act (ACA), either subsidized coverage in new
      marketplaces, or through Medicaid if all states were to implement expansion. (4)
      While over half of the uninsured in both rural and urban areas are younger than
      40 years, the uninsured in rural areas are disproportionately older across all
      income categories, which reflects the age distribution in the population.

PMID- 25399468
TI  - Medicare Accountable Care Organizations: program eligibility, beneficiary
      assignment, and quality measures.
AB  - Accountable Care Organizations (ACOs) are groups of providers (generally
      physicians and/or hospitals) that may receive financial rewards by maintaining or
      improving care quality for a group of patients while reducing the cost of care
      for those patients. The Patient Protection and Affordable Care Act of 2010 (ACA)
      established a Medicare Shared Savings Program (MSSP) and accompanying Medicare
      ACOs to "facilitate coordination and cooperation among providers to improve the
      quality of care for Medicare fee-for-service (FFS) beneficiaries and reduce
      unnecessary costs." The MSSP now includes 343 ACOs; an additional 23 ACOs
      participate in the Medicare Pioneer ACO demonstration program, and there are
      approximately 240 private ACOs. Based on our analysis, among the Medicare ACOs
      119 operate in both rural and urban counties and seven operate exclusively in
      rural counties. A little over 24 percent of non-metropolitan counties are
      included in Medicare ACOs. To assist rural providers considering ACO formation,
      this policy brief describes MSSP eligibility and participation requirements,
      beneficiary assignment processes, and quality measures.

PMID- 25399469
TI  - Extent of telehealth use in rural and urban hospitals.
AB  - Key Findings. Data from 4,727 hospitals in the 2013 HIMSS Analytics database
      yielded these findings: (1) Two-thirds (66.0% of rural defined as nonmetropolitan
      and 68.0% of urban) had no telehealth services or were only in the process of
      implementing a telehealth application. One-third (34.0%rural and 32.0% urban) had
      at least one telehealth application currently in use. (2) Among hospitals with
      "live and operational" telehealth services, 61.4% indicated only a single
      department/program with an operational telehealth service, and 38.6% indicated
      two or more departments/programs with operational telehealth services. Rural
      hospitals were significantly less likely to have multiple services (35.2%) than
      were urban hospitals (42.1%) (3) Hospitals that were more likely to have
      implemented at least one telehealth service were academic medical centers, not
      for-profit institutions, hospitals belonging to integrated delivery systems, and
      larger institutions (in terms of FTEs but not licensed beds). Rural and urban
      hospitals did not differ significantly in overall telehealth implementation
      rates. (4) Urban and rural hospitals did differ in the department where
      telehealth was implemented. Urban hospitals were more likely than rural hospitals
      to have operational telehealth implementations in cardiology/stroke/heart attack
      programs (7.4% vs. 6.2%), neurology (4.4% vs. 2.1%), and
      obstetrics/gynecology/NICU/pediatrics (3.8% vs. 2.5%). In contrast, rural
      hospitals were more likely than urban hospital to have operational telehealth
      implementations in radiology departments (17.7% vs. 13.9%) and in
      emergency/trauma care (8.8% vs. 6.3%).

PMID- 25399470
TI  - A guide to understanding the variation in premiums in rural health insurance
      marketplaces.
AB  - Key Findings. (1) State-level decisions in implementing the Patient Protection
      and Affordable Care Act of 2010 (ACA) have led to significant state variation in
      the design of Health Insurance Marketplace (HIM) rating areas. In some designs,
      rural counties are grouped together, while in others, rural and urban counties
      have been deliberately mixed. (2) Urban counties have, on average, approximately
      one more firm participating in the marketplaces, representing about 11 more plan
      offerings, than rural counties have. (3) The highest-valued "platinum" plan types
      are less likely to be available in rural areas. Thus, the overall mix of plan
      types should be factored into the reporting of average premiums. (4) Levels of
      competition are likely to have a greater impact on the decisions of firms
      considering whether to operate in higher-cost areas or not, as those firms must
      determine how they can pass such costs on to consumers, conditional on the market
      share they are likely to control.

PMID- 25399471
TI  - Trends in hospital network participation and system affiliation, 2007-2012.
AB  - Key Findings. (1) Hospital network participation from 2007 to 2012 increased in
      larger hospitals (more than 150 beds), non-government not-for-profit hospitals,
      and metropolitan hospitals. Network participation changed inconsistently in other
      types of hospitals. (2) Hospital system affiliation has generally increased in
      hospitals of all sizes, non-government not-for-profit hospitals, hospitals in all
      census regions, CAHs, and both metropolitan and nonmetropolitan hospitals. There
      are notably higher percentages of system affiliation among midsized and large
      hospitals, investor-owned hospitals, and metropolitan hospitals compared to their
      counterparts.

PMID- 25399472
TI  - Update: independently owned pharmacy closures in rural America, 2003-2013.
AB  - Key Findings. (1) From March 2003 to December 2013, there was a loss of 924
      (12.1%) independently owned rural pharmacies in the United States. The most
      drastic loss occurred between 2007 and 2009. From 2010-2013, the trend has been
      for more closures, although the decline is not as pronounced or clear as in
      earlier years. (2) Four hundred ninety rural communities that had one or more
      retail pharmacy (including independent, chain, or franchise pharmacy) in March
      2003 had no retail pharmacy in December 2013.

PMID- 25399473
TI  - The effect of Medicare payment policy changes on rural primary care practice
      revenue.
AB  - In this policy brief we analyze the effect of Medicare payment adjustments on
      Medicare-derived revenues to rural primary care providers. Building on prior work
      in this area, we look at the effect of changes in the Geographic Practice Cost
      Indices (GPCIs) from 2013 to 2014 as implemented in the Pathway for SGR Reform
      Act of 2013 and the Protecting Access to Medicare Act. Key Findings. (1) Changes
      to the GPCIs made between January 1, 2013, and March 31, 2014, resulted in an
      average 0.12% (median 0.18%) Medicare-derived revenue increase in rural primary
      care practices. (2) Without the GPCI work floor reinstatement, primary care
      practices in rural areas would have been disproportionately impacted through
      lower Medicare-related revenues.

PMID- 25399474
TI  - Facilitating the formation of accountable care organizations in rural areas.
AB  - This Policy Brief presents characteristics contributing to the formation of four
      accountable care organizations (ACOs) that serve rural Medicare beneficiaries.
      Doing so provides considerations for provider organizations contemplating
      creating rural-based ACOs. Key Findings. (1) Previous organizational integration
      and risk-sharing experience facilitated ACO formation. (2) Use of an electronic
      health record system fostered core ACO capabilities, including care coordination
      and population health management. (3) Partnerships across the care continuum
      supported utilization of local health care resources.

PMID- 25399475
TI  - Geographic variation in premiums in health insurance marketplaces.
AB  - This policy brief analyzes the 2014 premiums associated with qualified health
      plans (QHPs) made available through new health insurance marketplaces (HIMs), an
      implementation of the Patient Protection and Affordable Care Act (ACA) of 2010.
      We report differences in premiums by insurance rating areas while controlling for
      other important factors such as the actuarial value of the plan (metal level),
      cost-of-living differences, and state-level decisions over type of rating area.
      While market equilibrium, based on experience and understanding of the
      characteristics of the new market, should not be expected this soon, preliminary
      results give policymakers key issues to monitor.

PMID- 25399476
TI  - Robert Weinstock, MD, 40th President of AAPL: Elder statesman of forensic
      psychiatry and rebel with a cause.

PMID- 25399477
TI  - Much accomplished, much more to achieve.

PMID- 25399478
TI  - Shaping the science of prevention.

PMID- 25399479
TI  - HIV vaccine funding declines, while cure funds rise.

PMID- 25399480
TI  - Neonatal testicular cell transplantation restores murine spermatogenesis damaged
      in the course of herpes simplex virus-induced orchitis.
AB  - Genital tract infection and inflammation may affect male fertility, causing germ
      and Sertoli cell loss. We determined if testicular cell transplantation is
      effective at repairing testicular injury induced by herpes simplex virus (HSV)
      orchitis. ROSA26 mice were used as donors and the recipients were C57BL/6 mice
      after HSV testicular inoculation; some of the recipients were treated with the
      antiviral drug acyclovir (ACV). ACV reduced the amount of HSV antigen in testes
      on Day 3 after transplantation and enhanced the efficacy of transplantation at
      Day 30. In recipient testes, donor Sertoli cells formed new seminiferous tubules;
      significantly more new tubules were observed in the testes of ACV-treated mice
      compared with mice not treated with ACV (17.8% vs 3.6%). Over half (50.4%) of new
      tubules in ACV-treated testes contained germ cells and round spermatids were
      detected in 14.2% of new tubules compared with 15.9% and 5.3% in testes not
      treated with ACV, respectively. At Day 150 the seminiferous epithelium was
      completely recovered in some donor tubules and elongated spermatids were observed
      inside it. Thus, our findings reveal the effectiveness of the combination of
      antiviral therapy with neonatal testis-cell transplantation for the restoration
      of spermatogenesis damaged by viral infection. 

PMID- 25399481
TI  - A randomized investigator-blind parallel-group study to assess efficacy and
      safety of azelaic acid 15% gel vs. adapalene 0.1% gel in the treatment and
      maintenance treatment of female adult acne.
AB  - BACKGROUND: Growing numbers of post-adolescent females are suffering from
      treatment-resistant or relapsing adult acne forms, therefore requiring the
      definition of safe and effective treatment options for this burdening disease.
      OBJECTIVES: To assess the efficacy of azelaic acid 15% gel (AzA) vs. no treatment
      during maintenance therapy of female adult acne and to compare its efficacy and
      safety vs. adapalene 0.1% gel (AD) during a 9-month period (3-month treatment and
      6-month maintenance treatment). METHODS: A total of 55 women between 18 and 45
      years with adult acne were included in this investigator-blind trial and
      randomized into three groups receiving AzA gel b.i.d. for 9 months (AzA9M, n =
      17) or AzA gel b.i.d. for 3 months followed by a 6-month observational phase
      (AzA3M, n = 19) or AD gel once daily for 9 months (AD9M, n = 19). Parameters of
      efficacy, safety and patient-related factors were analysed. RESULTS: The
      reduction in lesion counts, severity and Dermatology Life Quality Index score was
      significant (P < 0.05) and comparable between groups during the treatment phase,
      while dryness and scaling were significantly lower (P < 0.05) in group AzA9M vs.
      AD9M. During maintenance, AzA9M was superior to AzA3M in the control of
      inflammatory lesions (P = 0.008) and total lesions (P = 0.014) at week 24. From
      week 12 to week 36, a mild relative increase in inflammatory lesions could be
      observed in all groups. In AzA3M, this increase exceeded that of AzA9M by 23.1%
      (P = 0.109), while the difference of total lesions diverged to 30.8% (P = 0.038).
      No significant differences could be detected between AzA9M and AD9M. Group AzA9M
      was non-inferior to AD9M (non-inferiority margin of 50% for the confidence limit
      for the relative effect) in the control of inflammatory acne lesions.
      CONCLUSIONS: AzA15% gel is a safe and effective treatment and maintenance
      treatment of female adult acne with non-inferior efficacy to AD 0.1% gel in the
      control of inflammatory acne.

PMID- 25399483
TI  - Systemic lupus erythematosus pancreatitis: an uncommon presentation of a common
      disease.
AB  - BACKGROUND: Acute pancreatitis is uncommon in systemic lupus erythematosus (SLE).
      When recognized early and properly treated with IV steroids and hydration, the
      course may be benign, as exemplified in the following report. CASE REPORT: A 21
      year-old woman with history of SLE and stage IV lupus nephritis, was admitted to
      the Sergio Bernales Hospital ICU (Lima, Peru), complaining of worsening
      epigastric pain radiating to the back, and nausea and vomiting for 1 week. She
      denied prior cholelithiasis, alcohol use, or recent medication changes. On
      examination, she was tachycardic and normotensive, with a slightly distended
      abdomen and epigastric tenderness on deep palpation, without signs of peritoneal
      irritation. Laboratory results demonstrated leukocytosis without left shift,
      creatinine of 2.26 mg/dL, amylase of 750 U/L, and lipase of 1038 U/L. Liver
      chemistries, calcium, lactic acid, triglycerides, and IgG4 were normal and
      alcohol level was undetectable. Ultrasound did not show cholelithiasis, biliary
      sludge, or common bile duct dilation. CT of the abdomen showed pancreas head
      (parenchyma) stranding with uniform enhancement consistent with interstitial
      pancreatitis. Despite receiving IV fluids, opiates, anti-emetics, and nothing by
      mouth, her clinical condition deteriorated, prompting the use of IV
      methylprednisolone. After completing 1 week of IV steroids, she was transferred
      to the medical floor clinically improved. The patient was discharged with an oral
      steroid taper and complete resolution of symptoms. CONCLUSIONS: After ruling out
      common causes, such as hepatobiliary pathology or toxin-related insults like
      alcohol, hypercalcemia, hypertriglyceridemia or medications, steroids may be used
      in SLE pancreatitis because they might improve the overall prognosis.

PMID- 25399484
TI  - Age-dependent trait variation: the relative contribution of within-individual
      change, selective appearance and disappearance in a long-lived seabird.
AB  - Within populations, the expression of phenotypic traits typically varies with
      age. Such age-dependent trait variation can be caused by within-individual change
      (improvement, senescence, terminal effects) and/or selective (dis)appearance of
      certain phenotypes among older age classes. In this study, we applied two methods
      (decomposition and mixed modelling) to attribute age-dependent variation in seven
      phenological and reproductive traits to within-individual change and selective
      (dis)appearance, in a long-lived seabird, the common tern (Sterna hirundo). At
      the population level, all traits, except the probability to breed, improved with
      age (i.e. phenology advanced and reproductive output increased). Both methods
      identified within-individual change as the main responsible process, and, within
      individuals, performance improved until age 6-13, before levelling off. In
      contrast, within individuals, breeding probability decreased to age 10, then
      levelled off. Effects of selective appearance and disappearance were small, but
      showed that longer-lived individuals had a higher breeding probability and bred
      earlier and that younger recruits performed better throughout life than older
      recruits in terms of both phenology and reproductive performance. In the year
      prior to death, individuals advanced reproduction, suggesting terminal
      investment. The decomposition method attributed more age-dependent trait
      variation to selective disappearance than the mixed-modelling method: 14-36%
      versus 0-8%, respectively, which we identify to be due to covariance between
      rates of within-individual change and selective (dis)appearance leading to biased
      results from the decomposition method. We conclude that the decomposition method
      is ideal for visualizing processes underlying population change in performance
      from one age class to the next, but that a mixed-modelling method is required to
      investigate the significance and relative contribution of age effects.
      Considerable variation in the contribution of the different age processes between
      the seven phenotypic traits studied, as well as notable differences between
      species in patterns of age-dependent trait expression, calls for better
      predictions regarding optimal allocation strategies with age. 

PMID- 25399485
TI  - Scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec
      reduced neonatal sepsis.
AB  - AIM: The aim of this study was to investigate whether scrubbing the hub of
      intravenous catheters with an alcohol wipe for 15 sec could reduce the incidence
      of neonatal sepsis in a level-three neonatal intensive care unit. METHODS: We
      studied the incidence of neonatal sepsis caused by coagulase-negative
      staphylococci (CoNS) for 16.5 months before the initiative was launched on May
      15, 2012 and then for a further 8.5 months after it was introduced. The hub
      routine was applied to all intravenous catheters. RESULTS: During the control
      period before the initiative was launched, there were nine cases of CoNS sepsis
      compared with no cases after it was introduced, resulting in a decrease in sepsis
      incidence from 1.5% to 0% with a risk reduction of 1.5% (0.53-2.58%) (p = 0.06).
      In the preterm infant population, the incidence of sepsis decreased from 3.6% to
      0% (1.1-6.0%) (p = 0.11). CONCLUSION: Scrubbing the hub of intravenous catheters
      with an alcohol wipe for 15 sec seemed to be an efficient way of preventing
      sepsis caused by CoNS in newborn infants. However, the evidence for the benefits
      will remain weak until a large randomised trial has been completed.

PMID- 25399486
TI  - Natural products with anti-Bredt and bridgehead double bonds.
AB  - Well over a hundred years ago, Professor Julius Bredt embarked on a career
      pursuing and critiquing bridged bicyclic systems that contained ring strain
      induced by the presence of a bridgehead olefin. These endeavors founded what we
      now know as Bredt's rule (Bredtsche Regel). Physical, theoretical, and synthetic
      organic chemists have intensely studied this premise, pushing the boundaries of
      such systems to arrive at a better understood physical phenomenon. Mother nature
      has also seen fit to construct molecules containing bridgehead double bonds that
      encompass Bredt's rule. For the first time, this topic is reviewed in a natural
      product context. 

PMID- 25399487
TI  - Hooking up during the college years: is there a pattern?
AB  - Hook ups are sexual encounters that can include a variety of behaviours (e.g.,
      kissing to intercourse) with no expectation of future contact or a committed
      relationship. Although hooking up is reported to be common on college campuses
      across the USA, little is known about whether the frequency of hooking up changes
      over the course of the college experience. Using cross-sectional data and the
      covariates alcohol use, gender and relationship status, we examined a synthetic
      cohort of undergraduate students (n = 1003) on rates of hooking up using (1)
      logistic regression and (2) an applied form of survival analysis. Whereas both
      analytic techniques produced similar results, survival analysis provided a more
      complete picture by showing an increase in the rate of hooking up that peaked
      between spring semester of the first year of college and autumn semester of the
      second year of college, followed by a gradual decline in hook up rates over
      subsequent semesters. Findings indicate that gender is significantly related to
      hooking up in the logistic regression analysis, with women reporting fewer hook
      ups; however, gender was not significantly related to hooking up in the survival
      analysis, indicating that there are no differences in the pattern across cohorts.
      Implications for promoting the sexual health of college students and future
      research are discussed. 

PMID- 25399488
TI  - Repeated inhalation of sevoflurane inhibits airway inflammation in an OVA-induced
      mouse model of allergic airway inflammation.
AB  - BACKGROUND AND OBJECTIVE: Repeated inhalation of sevoflurane (SVF) can benefit
      asthmatic patients by bronchodilation. However, the impact of repeated inhalation
      of SVF on allergic airway inflammation has not been clarified. This study was
      aimed at investigating the effects of repeated inhalation of SVF on airway
      inflammation in mice. METHODS: Female C57BL/6 mice were sensitized with ovalbumin
      (OVA) and treated by inhalation with SVF or vehicle daily for seven consecutive
      days, immediately followed by OVA challenge. Airway inflammation was evaluated by
      counting the numbers of different types of inflammatory infiltrates in
      bronchoalveolar lavage fluid (BALF), histology, cytokine measurements and mucus
      production in individual mice. RESULTS: In comparison with the OVA group,
      repeated inhalation of SVF significantly reduced the numbers of total cells,
      eosinophils, lymphocytes, macrophages and neutrophils (P < 0.05 to P < 0.01), and
      the levels of BALF tumour necrosis factor-alpha and lung high-mobility group box
      1 (P < 0.01), accompanied by elevated levels of BALF interleukin-10 in allergic
      mice (P < 0.05). Repeat inhalation of SVF decreased the levels of serum OVA
      specific immunoglobulin E (IgE) and mitigated allergic airway epithelial goblet
      cell hyperplasia and mucus hypersecretion in allergic mice (P < 0.01).
      CONCLUSIONS: Repeated inhalation of SVF inhibits allergic airway inflammation by
      reducing inflammatory infiltrates, improving the imbalance of cytokine responses
      and mitigating allergen-specific IgE responses and goblet cell hyperplasia in
      mice.

PMID- 25399489
TI  - A proposed role for routine EEGs in patients with consciousness disorders.

PMID- 25399504
TI  - Host behaviour manipulation as an evolutionary route towards attenuation of
      parasitoid virulence.
AB  - By definition, insect parasitoids kill their host during their development. Data
      are presented showing that ladybirds not only can survive parasitism by
      Dinocampus coccinellae, but also can retain their capacity to reproduce following
      parasitoid emergence. We hypothesize that host behaviour manipulation constitutes
      a preadaptation leading to the attenuation of parasitoid virulence. Following
      larval development, the parasitoid egresses from the host and spins a cocoon
      between the ladybird's legs. Throughout parasitoid pupation, the manipulated host
      acts as a bodyguard to protect the parasitoid cocoon from predation. The
      parasitoid has evolved mechanisms to avoid killing the host prematurely so that
      its own survival is not compromised. Bodyguard manipulation may thus constitute a
      selective trait for the evolution of true parasitism in some host-parasitoid
      associations. 

PMID- 25399490
TI  - Platinum sensitivity and CD133 expression as risk and prognostic predictors of
      central nervous system metastases in patients with epithelial ovarian cancer.
AB  - BACKGROUND: To characterize prognostic and risk factors of central nervous system
      (CNS) metastases in patients with epithelial ovarian cancer (EOC). METHODS: A
      retrospective analysis of Xijing Hospital electronic medical records was
      conducted to identify patients with pathologically confirmed EOC and CNS
      metastases. In addition to patient demographics, tumor pathology, treatment
      regimens, and clinical outcomes, we compared putative cancer stem cell marker
      CD133 expression patterns in primary and metastatic lesions as well as in
      recurrent EOC with and without CNS metastases. RESULTS: Among 1366 patients with
      EOC, metastatic CNS lesions were present in 29 (2.1%) cases. CD133 expression in
      primary tumor was the only independent risk factor for CNS metastases; whilst the
      extent of surgical resection of primary EOC and platinum resistance were two
      independent factors significantly associated with time to CNS metastases. Absence
      of CD133 expression in primary tumors was significantly associated with high
      platinum sensitivity in both patient groups with and without CNS metastases.
      Platinum resistance and CD133 cluster formation in CNS metastases were associated
      with decreased survival, while multimodal therapy including stereotactic
      radiosurgery (SRS) for CNS metastases was associated with increased survival
      following the diagnosis of CNS metastases. CONCLUSIONS: These data suggest that
      there exist a positive association between CD133 expression in primary EOC,
      platinum resistance and the increased risk of CNS metastases, as well as a less
      favorable prognosis of EOC. The absence of CD133 clusters and use of multimodal
      therapy including SRS could improve the outcome of metastatic lesions. Further
      investigation is warranted to elucidate the true nature of the association
      between platinum sensitivity, CD133 expression, and the risk and prognosis of CNS
      metastases from EOC.

PMID- 25399506
TI  - Genetic variation in inflammatory and bone turnover pathways and risk of
      osteolytic responses to prosthetic materials.
AB  - Wear particle-induced inflammatory bone loss (osteolysis) is the leading cause of
      total hip arthroplasty (THA) failure. Individual susceptibility to osteolysis is
      modulated by genetic variation. In this 2-stage case-control association study we
      examined whether variation within candidate genes in inflammatory and bone
      turnover signaling pathways associates with susceptibility to osteolysis and time
      to prosthesis failure. We examined two cohorts, comprising 758 (347 male)
      Caucasian subjects who had undergone THA with a metal on polyethylene bearing
      couple; 315 of whom had developed osteolysis. Key genes within inflammatory, bone
      resorption, and bone formation pathways were screened for common variants by
      pairwise-SNP tagging using a 2-stage association analysis approach. In the
      discovery cohort four SNPs within RANK, and one each within KREMEN2, OPG, SFRP1,
      and TIRAP (p < 0.05) were associated with osteolysis susceptibility. Two SNPs
      within LRP6, and one each within LRP5, NOD2, SOST, SQSTM1, TIRAP, and TRAM
      associated with time to implant failure (p < 0.05). Meta-analysis of the two
      cohorts identified four SNPs within RANK, and one each within KREMEN2, OPG,
      SFRP1, and TIRAP associated with osteolysis susceptibility (p < 0.05). Genetic
      variation within inflammatory signaling and bone turnover pathways may play a
      role in susceptibility to osteolysis.

PMID- 25399505
TI  - Longitudinal associations between temperament and socioemotional outcomes in
      young children: the moderating role of RSA and gender.
AB  - Temperament is an important predictor of socioemotional adjustment, such as
      externalizing and internalizing symptoms. However, there is not a one-to-one
      correspondence between temperamental predispositions and these outcomes, implying
      that other factors also contribute to the development of internalizing and
      externalizing problems. Self-regulation is believed to interact with temperament,
      and has been studied as a predictor for later socioemotional outcomes.
      Respiratory sinus arrhythmia (RSA) is a psychophysiological measure of self
      regulation that has been studied as a moderator of risk. The primary aim of the
      present study was to test if RSA baseline and RSA reactivity would moderate the
      link between temperament and socioemotional outcomes. Mothers reported the
      temperament of their infants (20 months; N = 154), RSA was collected at 24- and
      42-months, and mothers reported externalizing and internalizing behaviors at
      kindergarten entry. RSA baseline and RSA reactivity moderated the relation
      between exuberant temperament and externalizing behaviors. However, these results
      were only significant for girls, such that high RSA baseline and greater RSA
      suppression predicted more externalizing behaviors when exuberance was high.
      Fearful temperament predicted later internalizing behaviors, but no moderation
      was present. These results are discussed in light of recent evidence regarding
      gender differences in the role of RSA as a protective factor for risk.

PMID- 25399507
TI  - Understanding thread properties for red blood cell antigen assays: weak ABO blood
      typing.
AB  - "Thread-based microfluidics" research has so far focused on utilizing and
      manipulating the wicking properties of threads to form controllable microfluidic
      channels. In this study we aim to understand the separation properties of
      threads, which are important to their microfluidic detection applications for
      blood analysis. Confocal microscopy was utilized to investigate the effect of the
      microscale surface morphologies of fibers on the thread's separation efficiency
      of red blood cells. We demonstrated the remarkably different separation
      properties of threads made using silk and cotton fibers. Thread separation
      properties dominate the clarity of blood typing assays of the ABO groups and some
      of their weak subgroups (Ax and A3). The microfluidic thread-based analytical
      devices (MUTADs) designed in this work were used to accurately type different
      blood samples, including 89 normal ABO and 6 weak A subgroups. By selecting
      thread with the right surface morphology, we were able to build MUTADs capable of
      providing rapid and accurate typing of the weak blood groups with high clarity. 

PMID- 25399508
TI  - Nanopatterned superlattices in self-assembled C2 -symmetric oligodimethylsiloxane
      based benzene-1,3,5-tricarboxamides.
AB  - The synthesis of C3 - and C2 -symmetric benzene-1,3,5-tricarboxamides (BTAs)
      containing well-defined oligodimethylsiloxane (oDMS) and/or alkyl side chains has
      been carried out. The influence of the bulkiness of the oDMS chains in the
      aggregation behavior of dilute solutions of the oDMS-BTAs in methylcyclohexane
      was studied by temperature-dependent UV spectroscopy. The formation of
      hierarchically self-assembled aggregates was observed at different BTA
      concentrations, the tendency of aggregation increases by shortening or removing
      oDMS chains. Chiral BTAs were investigated with circular dichroism (CD)
      spectroscopy, showing a stronger tendency to aggregate than the achiral ones.
      Majority rules experiments show a linear behavior consistent with the existence
      of a high mismatch penalty energy. The most efficient oDMS-BTAs organogelators
      have the ability to form stable organogels at 5 mg mL(-1) (0.75 wt %) in hexane.
      Solid-state characterization techniques indicate the formation of an
      intermolecular threefold hydrogen bonding between adjacent molecules forming
      thermotropic liquid crystals, exhibiting a hexagonal columnar organization from
      room temperature to above 150  degrees C. A decrease of the clearing temperatures
      was observed when increasing the number and length of the oligodimethylsiloxane
      chains. In addition to the three-fold hydrogen bonding that leads to columnar
      liquid crystalline phase, segregation between the oDMS and aliphatic chains takes
      place in the BTA functionalized with two alkyl and one oDMS chain leading to a
      superlattice within the hexagonal structure with potential applications in
      lithography. 

PMID- 25399510
TI  - Risk factors for hepatitis E virus infection and disease.
AB  - Hepatitis E, caused by hepatitis E virus, is a disease of global significance,
      causing 20 million infections each year. Genotypes 1 and 2 have vastly different
      epidemiological patterns from genotypes 3 and 4. In genotype 1 and 2 endemic
      areas, most infections and illness occur in persons 15-30 years of age, with
      pregnant women being the most likely to experience severe disease. In genotype 3
      and 4 endemic areas, most infections and illness occur in those of age 40-60
      years, with males representing a large portion of those with severe disease.
      However, the lack of an easily accessible serologic assay in many countries
      continues to be a barrier to the diagnosis and recognition of hepatitis E virus. 

PMID- 25399509
TI  - Optimization of potent and selective quinazolinediones: inhibitors of respiratory
      syncytial virus that block RNA-dependent RNA-polymerase complex activity.
AB  - A quinazolinedione-derived screening hit 2 was discovered with cellular antiviral
      activity against respiratory syncytial virus (CPE EC50 = 2.1 MUM), moderate
      efficacy in reducing viral progeny (4.2 log at 10 MUM), and marginal cytotoxic
      liability (selectivity index, SI ~ 24). Scaffold optimization delivered analogs
      with improved potency and selectivity profiles. Most notable were compounds 15
      and 19 (EC50 = 300-500 nM, CC50 > 50 MUM, SI > 100), which significantly reduced
      viral titer (>400,000-fold), and several analogs were shown to block the activity
      of the RNA-dependent RNA-polymerase complex of RSV. 

PMID- 25399512
TI  - Are IL2 promoter polymorphisms associated with MS in Iranian patients? - We do
      not know.

PMID- 25399511
TI  - Soil fungal communities respond to grassland plant community richness and soil
      edaphics.
AB  - Fungal communities in soil have significant influences on terrestrial ecosystem
      dynamics, yet our understanding of the drivers of fungal diversity and community
      structure in soil is limited. Fungal communities associated with the rhizosphere
      of four native perennial grassland plant species, two legumes and two grasses,
      grown in monoculture and polyculture in a long-term field experiment were
      characterized. Reference databases were developed for, and amplicon libraries
      sequenced from, multiple-copy rRNA and single-copy protein-coding loci.
      Clustering and alignment-based pipelines were utilized to evaluate differences in
      fungal community structure and diversity in response to plant host, plant
      community richness, and soil edaphics. Fungal diversity increased in the
      rhizosphere of plants growing in polyculture plant communities as compared to
      monoculture plant communities. Fungal community structure was differentiated
      between legumes and grasses growing in monoculture but not in polyculture. To
      specifically monitor fungi in the genus Fusarium in the soil, the protein-coding
      locus was used to increase phylogenetic resolution and enrich for this taxon.
      These data show that fungal community richness and structure are strongly linked
      with plant community dynamics and associated soil edaphic characteristics in
      these grassland soils. 

PMID- 25399513
TI  - What carers and family said about music therapy on behaviours of older people
      with dementia in residential aged care.
AB  - AIM: This study sought to evaluate the effectiveness of group music therapy (MT)
      intervention on behaviours of older people with dementia. METHOD: Reported here
      are qualitative data from five, semi-structured focus groups; two comprising a
      total of seven family members and three comprising a total of 23 staff members.
      RESULTS: A number of core themes emerged: temporality, effect and policy with a
      number of subthemes. The MT effect is tempered by the temporality of (i) the
      older person's dementia state, (ii) the session and (iii) the psychosomatic
      effect on the older person. Music therapy is perceived to (i) evoke memories and
      facilitate reminiscence, (ii) act as a diversion (has an instrumental value) and
      it is contentious to discount the (iii) dichotomy between music and therapist in
      terms of the overall effect. Finally, policymakers need to know that MT is (i)
      highly prized and more, not less, MT is recommended. CONCLUSION: Findings from
      this study illustrate that the timing of the MT session has consequences for the
      workflow in the residential aged care facility; MT has a psychosomatic effect and
      participants here evaluate this as temporal. Care providers and family members
      acknowledge the instrumental value of MT and its helping with cognition and
      exercise. They have mixed views about the effects of the music and the effect on
      the older person by the therapist but most definitely want policymakers to ensure
      more, not less, planned and better funded MT is part of ongoing care in the
      residential aged care context. Areas for future research and policy are also
      highlighted. IMPLICATIONS FOR PRACTICE: These views on group MT in residential
      aged care can initiate critical reflection on current practices and systems.
      Research is needed exploring the timing and scheduling of MT sessions at
      different times in the day for older person with dementia exhibiting negative
      behaviours.